PMID- 14633450
TI  - [Detection of COL1A1/PDGFB fusion transcripts in dermatofibroscoma protuberans by
      revers transcriptase-polymerase chain reaction using paraffin-embedded tissues].
AB  - OBJECTIVE: To detect the COL1A1/PDGFB fusion transcripts and discuss its
      clinicopathological significance in dermatofibroscoma protuberans. METHODS:
      Formalin fixed, paraffin-embedded tumor specimens from 12 patients with DFSP were
      reviewed by light microscope and the expression of COL1A1/PDGFB mRNA resulting
      from the reciprocal translocation t(17;22) (q22;q13.1) was detected by one-step
      revers transcriptase-polymerase chain reaction. The following tumor specimens
      were included as controls: 2 fibrosarcoma, 2 malignant fibrous histocytoma, 3
      leiomyosarcoma, 1 dermarofibroma and 1 nerve shealth tumor. RESULTS: The
      COL1A1/PDGFB fusion transcripts were detected in 8 (67%) of 12 samples from
      patients with DFSP. Nucleotide sequence analysis using the PCR products confirmed
      that different regions of the COL1A1 gene, respectively, were fused with of PDGFB
      gene. No COL1A1/PDGFB fusion transcripts were detected in the control tumors.
      CONCLUSION: Detection of specific COL1A1/PDGFB fusion transcripts in DFSP will
      help to diagnose the nature of DFSP and research the mechanism of its molecular
      histogenesis.

PMID- 14633451
TI  - [Study on the diagnostic significance of detecting the expression of AChR-gamma
      mRNA in rhabdomyosarcoma tissues].
AB  - OBJECTIVE: To detect over-expression of AChR-gamma mRNA in rhabdomyosarcoma
      tissues by duplex RT-PCR and discuss its potential in diagnosis of
      rhabdomyosarcoma. METHODS: Duplex RT-PCR was applied to the simultaneous
      detection of AChR-alpha and gamma subunit messenger RNA in 17 cases of
      rhabdomyosarcoma (9 ERMS, 6 ARMS, 2 PRMS). 20 cases of non-rhabdomyosarcomous
      small round cell tumors (6 poorly differentiated synovial sarcomas, 6 ES/PNET, 6
      lymphomas, 2 neuroblastomas) and three normal muscle samples were also detected
      for AChR-alpha and gamma mRNA by the same method. RESULTS: AChR-alpha and AChR
      gamma mRNA were expressed in all the cases of rhabdomyosarcoma. The rate of
      quantity in both transcripts was AChR-gamma/AChR-alpha >or= 1, but the rate for
      three normal muscle samples was < 1. Cases of non-rhabdomyosarcomous small round
      cell tumors were all negative for AChR-gamma. CONCLUSION: AChR-gamma mRNA
      expression detected by molecular genetic methods is useful in diagnosis and
      differential diagnosis of rhabdomyosarcoma.

PMID- 14633452
TI  - [Clinicopathologic analysis of 154 cases of tumors and tumor-like lesions in the
      bones of hands and feet].
AB  - OBJECTIVE: To study the clinical and pathologic features of tumors and tumor-like
      lesions in the bones of hands and feet. METHODS: Clinical, X-ray and pathologic
      features of 154 cases of tumors and tumor-like lesions in the bones of hands and
      feet between 1991 and 2002 were investigated. RESULTS: In the bones of hands and
      feet the frequency and distribution of many lesions were distinctive when
      compared to those of other skeletal sites. Cartilaginous lesions were most common
      (60%), and 72% of them were enchondromas. Enchondromas were most often situated
      in the second to fifth phalanges and metacarpal bones. Chondroblastomas most
      frequently involved the irregular bones (such as calcaneus, talus and
      osnaviculare) of the feet. Whereas the occurance of osteochondromas in the bones
      of the hands and feet was lower than in the long bones. Most "osteochondromas" of
      the phalanges were subungual exostoses. A group of reactive or reparative
      lesions, which are related to trauma, such as subungual exostosis, giant cell
      reparative granuloma, florid reactive periostitis and bizarre parosteal
      osteochondromatous proliferations typically occurred in the bones of the hands
      and feet, but these tumor-like lesions were often misdiagnosted. Another feature
      of lesions in the bones of the hands and feet was that there were much more
      benign than malignant lesions (21:1), and that chondrosarcomas were common in
      malignancies. The diagnostic criteria for benign and malignant cartilaginous
      tumors in the bones of hands and feet were different from those in long bones and
      flat bones. CONCLUSIONS: Bone tumors of the hands and feet are different from
      that of long bones, flat bones and axial bones. Because the hands and feet are
      frequently exposed to trauma, reactive and reparative lesions often occur in
      these sites. These tumor-like lesions may simulate benign and malignant
      neoplasia. Knowledge of different types of lesions which commonly affect these
      sites is of benefit in assessing lesions of the bones of hands and feet.

PMID- 14633453
TI  - [Clinicopathological, immunohistochemical and molecular genetic study of intra
      abdomen extra-gastrointestinal stromal tumors].
AB  - OBJECTIVE: To explore the clinicopathological, immunohistochemical and molecular
      genetic features of intra-abdomen extra-gastrointestinal stromal tumors (EGISTs)
      and their differential diagnosis. METHODS: Nine cases of EGISTs from the
      abdominal cavity or retroperitoneum which were previously diagnosed as leiomyoma,
      leiomyoblastoma, or leiomyosarcoma etc. by a panel of antibodies such as CD117,
      CD34, alpha-SMA, MSA, desmin, S-100, and PGP9.5 from which five cases were
      detected for c-kit gene mutation. RESULTS: The tumors occurred in 5 men and 4
      women, the age ranged from 38 to 72 years (mean 61.7 years). Four cases arose
      from the mesentery, two from omentum, two from retroperitoneum and one located at
      the hilus of the spleen. The size of tumors ranged from 5 cm to 23 cm (mean 12.9
      cm) in diameter and the tumor cell components varied: mainly spindle cells (seven
      cases), epithelioid cells (one case), mixed cells (one case). Tumors expressed
      CD117 (8/9), CD34 (5/9), alpha-SMA (3/9), MSA (4/9), desmin (0), S-100 protein
      (1/9) and PGP9.5 (1/9). Of the five cases examined for heterozygous deletion
      mutation of 11 exon of the c-kit gene two were found positive. Two borderline
      cases showed long-term survival of 8 years and 11 years, respectively. In seven
      malignant cases, two showed adverse outcome, one survived 4 years without
      recurrence, two were lost in follow up and two new cases were still being in
      followed. CONCLUSIONS: GIST-type stromal tumors can also occur in the abdomen,
      most cases were borderline or malignant, tumor coagulative necrosis, mitoses >or=
      5 per 50 high-power fields and obvious nuclear atypia indicating malignancy.
      Differential diagnosis of EGIST including benign or malignant smooth muscle
      tumors, benign or malignant nerve sheath tumors etc.

PMID- 14633454
TI  - [Angiogenesis in coronary atherosclerotic plaques and its relationship to plaque
      stabilization].
AB  - OBJECTIVE: To compare the angiogenesis in unstable and stable plaques and to
      investigate the potential role of neovessels in creating vulnerable sites for
      atherosclerotic plaques. METHODS: Specimens of coronary arteries were obtained
      from 52 autopsy cases with acute coronary syndromes. Plaque morphology was
      studied by use of stained slides. 922 tissue blocks of late-stage lesions were
      classified into two groups: (1) unstable plaque (n = 153), the plaque was
      characterized by a large extracellular lipid core (more than 40% of the plaque
      area); (2) stable plaque (n = 769), lipid core less than 40% of the plaque area.
      Forty blocks were selected randomly from each group and serial sections were
      stained immunohistochemically with a polyclonal antibody against F VIII RAg.
      Computer-aided planimeter was used for quantitative analysis. RESULTS: In
      unstable plaques, the occurrence of neovessels was more frequent and the
      neovessel density (number/mm(2)) was significantly increased as compared to that
      of stable plaques (frequency: 80.4% vs 66.6%, P < 0.01; shoulder: 22.16 +/- 19.96
      vs 10.04 +/- 11.52, base: 21.68 +/- 20.44 vs 9.68 +/- 11.52, fibrous cap: 3.80 +/
      5.32 vs 1.48 +/- 2.28, P < 0.05). Most neovessels were located in the shoulder
      region and at the base of plaques. CONCLUSIONS: These findings suggest that
      neovessels in coronary atherosclerotic plaques are closely associated with the
      decreased stabilization of the plaques.

PMID- 14633455
TI  - [Study on pathological features and diagnosis, differential diagnosis of
      olfactory neuroblastoma].
AB  - OBJECTIVE: To observe the common characteristics of pathological morphology and
      immunohistochemical staining of olfactory neuroblastoma (ONB), and to raise the
      diagnostic ability for ONB. METHODS: 34 cases of ONB, 11 cases of
      rhabdomyosarcoma (RMS) and 76 cases of malignant lymphoma (ML) were collected,
      the clinical information were investigated, and the biopsy samples were stained
      and observed as follows: (1) Routine HE staining and viewed under the light
      microscope. (2) Expression of neuron-specific enolase (NSE), chromogranin-A
      (CgA), leukocyte common antigen (LCA), desmin, and sarcometic actin (S-actin)
      were determined in both ONB and RMS cases. In addition, S-100 protein,
      cytokeratin (AE1/AE3) were detected in the ONB and myoglobulin detected in the
      RMS. ML samples were stained for LCA, CD45RO, CD56, and CD20. The NSE, CgA,
      desmin and S-actin were stained in 10 cases of NK/T cell ML and 9 cases of B cell
      ML additionally. (3) 4 cases of ONB, RMS and ML were observed under transmission
      electron microscope respectively. RESULTS: The ages and clinical manifestations
      of ONB, RMS and ML were similar. The morphological characteristics of ONB
      included epithelial nests; net of angioma-like fibrous connective tissues; small
      round cells and small short spindle cells and nucleus; glandular and squamous
      liked epithelium; Homer-Wright and Flexner rosette; bunch of neurofibrilla, etc.
      NSE and CgA were expressed in small cells. S-100 protein was positive in the area
      of bunch of neurofibrilla. AE1/AE3 was positive in epithelial cells, LCA, while
      desmin and S-actin were all negative. Ultrastructurelly, there were
      neurosecretory granules and neurofibrilla in the cytoplasm of a few tumor cells.
      Although there were some similarities among ONB, RMS and ML under the light
      microscope, their characteristics of pathologic morphology, immunohistochemical
      staining and transmission electron microscope were different. CONCLUSIONS: The
      features of the morphological changes are the most important basis to make
      diagnosis for ONB. The results of immunohistochemical staining can verify it
      further and play an important role in its differential diagnosis. Transmission
      electron microscope is very important but not essential for its diagnosis.

PMID- 14633456
TI  - [Study on the status of cell differentiation in nasal NK/T-cell lymphomas].
AB  - OBJECTIVE: To evaluate the status of cell differentiation in nasal NK/T cell
      lymphomas. METHODS: The clinical data of 88 cases of NK/T cell lymphomas were
      collected. Antibodies to the following antigens were used in the
      immunohistochemical study: T cell differentiation antigens (CD3epsilon, CD5 and
      CD1a); NK cell associated antigens (CD56, CD57) and antibodies of CD34 and CD38.
      RESULTS: (1) Clinicopathology: clinically, frequently involved sites were the
      nasal cavity and the pharynx. Ulceration and erosion of the mucosa were common
      signs. Pathologically, diffuse infiltration of the tumor cells was observed in 68
      of 88 (70.45%) cases of nasal NK/T cell lymphomas. In 71 (80.68%) cases
      infiltrated cells were predominantly medium to large sized; (2) Differentiation
      status of tumor cells: the tumor cells expressed CD3epsilon in 78/88 (88.64%);
      CD5 in 56/88 (63.63%), CD56 in 25/88 (28.41%) and no positivity for CD1a, CD57,
      CD34 and CD38. CONCLUSION: Status of tumor cell differentiation in nasal NK/T
      cell lymphoma may have passed the stage of progenitor cell differentiation but
      not yet to the stage of mature T or NK cells.

PMID- 14633457
TI  - [Immunohistochemical demonstration of cyclins A, B, D1, D3 and E in
      hepatocellular carcinomas using tissue microarrays].
AB  - OBJECTIVE: To investigate the expression of five kinds of cyclins in
      hepatocellular carcinoma (HCC) and their association with degree of tumor
      differentiation, metastasis and infection of hepatitis B virus (HBV). METHODS:
      The HCC tissue microarrays were composed of those from 273 cases of HCC tissues,
      144 surrounding-tumor liver tissues and 10 normal liver tissues obtained from
      autopsy. The diameter of each specimens on tissue microarrays was 2.0 mm.
      Immunohistochemistry was used to detect the expression of cyclin A, cyclin B,
      cyclin D1, cyclin D3 and cyclin E on HCC tissue microarrays. The association of
      the expression of these cyclins with the infection rate of HBV was also analyzed.
      RESULTS: Three paraffin-embedded HCC tissue microarrays were successfully
      constructed, including 136, 143 and 148 tissue spots, respectively. The positive
      rates of cyclins in 273 cases of HCC were cyclin A 52.7%, cyclin B 45.4%, cyclin
      D1 35.9%, cyclin D3 44.3% and cyclin E 23.1%; while the figures in 144
      surrounding-tumor tissues were 8.3%, 5.6%, 4.9%, 6.3% and 1.4%, respectively. In
      10 normal liver tissues these cyclins exhibited negative staining, with the
      exception that cyclin D1 was positive in one case of normal liver tissue. The
      positive rate of cyclins in HCC were significant higher than those in surrounding
      tumor liver tissues (P < 0.01), in HCC tissues with histological grade II and
      III, the cyclins expression were stronger than that in grade I (P < 0.05). The
      positive rates of cyclins, except cyclin A in HCC with portal vein invasion were
      higher than those without portal vein invasion (P < 0.01). Infection of HBV did
      not have significant relationship with the expression of cyclins (P > 0.05).
      CONCLUSION: Cyclins in different cell cycles overexpressed at varied levels in
      hepatocellular carcinoma, and the increased expression of cyclins may shorten the
      tumor cell cycle phase, accelerate cell proliferation, and have a close
      relationship with HCC aggressiveness.

PMID- 14633458
TI  - [The antagonistic effect on anti-thy-1 serum-induced nephritis of rats injected
      by decorin-transfected mesangial cells vector].
AB  - OBJECTIVES: To inject decorin-transfected mesangial cells (MsC) vector into the
      kidneys of rats with anti-thy-1 serum-induced nephritis via left renal artery and
      observe the survival condition of MsC vector and its influence on glomerular
      lesions in rats with anti-thy-1 serum induced nephritis. METHODS: Rat mesangio
      proliferative glomerulonephritis was established by tail intravenous injection
      with rabbit anti-thy-1 serum (ATS). Decorin-transfected MsC was injected into rat
      kidneys via left renal artery. Primary culture, immunostaining for BrdU and
      decorin of transfected MsC lines were performed to observe their survival.
      Immunohistochemistry with image analysis was performed to detect the expression
      of BrdU, alpha-SMA, decorin, TGF-beta1, FN and ColIV in diseased glomeruli.
      RESULTS: Rat anti-thy-1 serum-induced nephritis identified by pathological
      examination was successfully established by injecting rabbit ATS, and decorin
      transfected MsC vector was transfused to rat glomeruli via left renal artery. The
      active growth and positive expressions of BrdU and decorin proteins on the nuclei
      and cytoplasms of ex vivo MsC were observed respectively. TGF-beta1, FN, ColIV
      expressions in diseased glomeruli of rats with ATS nephritis were decreased
      significantly at day 4 (TGF-beta1, P < 0.05) and day 2 (FN and ColIV, P < 0.01)
      respectively, compared to uninjected kidneys. CONCLUSIONS: MsC vector is
      successfully transferred to the glomeruli of experimental rats via left renal
      artery injection with no affect on cell survival. Decorin protein is expressed on
      the transfected MsC and shows antagonistic effect on the glomerular lesions of
      ATS rats. It suggests that the use of ex vivo MsC vector system can provide
      useful experimental basis for gene therapy of kidney disease in animal model.

PMID- 14633459
TI  - [Lipopolysaccharide induces expression of macrophage inflammatory protein-1alpha
      in human umbilical vein endothelial cells].
AB  - OBJECTIVE: To understand whether endotoxin lipopolysaccharide (LPS) is able to
      induce the expression of macrophage inflammatory protein-1alpha (MIP-1alpha) mRNA
      and protein in human umbilical vein endothelial cells (HUVECs). METHODS: The
      expression of MIP-1alpha mRNA was determined by dot blotting analysis and by in
      situ hybridization using a digoxigenin-labeled MIP-1alpha cDNA probe after
      exposure of the cultured HUVECs to LPS at different concentrations. The
      expression of MIP-1alpha mRNA was determined by RT-PCR as well. In addition, the
      expression of MIP-1alpha protein was tested by cell enzyme-linked immunosorbent
      assay (ELISA) using a goat anti-human monoclonal MIP-1alpha antibody. RESULTS:
      Dot blotting showed that the absorbance values of the dots on the nitrocellulose
      membrane were 1.490 and 3.310 when exposed to LPS at the concentrations of 1
      micro g/ml and 10 micro g/ml which were 1.97- and 4.38-fold over that of the
      control group (0.775), respectively. In situ hybridization revealed that exposure
      to LPS at a concentration of 1 micro g/ml led to a significant increase in the
      MIP-1alpha mRNA expression in HUVECs as compared to the control group (F =
      142.83, P < 0.01), whereas the MIP-1alpha mRNA in HUVECs was somewhat decreased
      when exposed to LPS at a concentration of 10 micro g/ml. RT-PCR revealed that the
      expression of MIP-1alpha mRNA in HUVECs were 1.65-, 2.86- and 1.26-fold over that
      of the control group when exposed to LPS at the concentrations of 1 micro g/ml, 5
      micro g/ml and 10 micro g/ml respectively. Cell ELISA showed that after exposure
      of the HUVECs to LPS at the concentrations mentioned above, the expression of MIP
      1alpha protein was strongly increased, especially in the 5 micro g/ml LPS group.
      Analysis of variance showed that there was a significant difference between
      groups (F = 15.36, P < 0.05). CONCLUSIONS: LPS may induce a high level of MIP
      1alpha mRNA and protein expression in HUVECs, and it might, hereby, play an
      important role in the recruitment of the monocytes/macrophages into the arterial
      intima.

PMID- 14633460
TI  - [The expression and clinical implication of gelatinase A in acute leukemic
      cells].
AB  - OBJECTIVE: To study the expression of gelatinase A (MMP2) in acute leukemic cells
      and its clinical implication. METHODS: The bone marrow samples from 46 acute
      leukemia patients were investigated by reverse transcription polymerase chain
      reaction (RT-PCR) and Gelatin Zymography method. Matrigel invasion assay was
      studied on U937, NB4, K562 and SHI1 cells in vitro. RESULTS: The expression of
      MMP2 was positive in 24 of 46 patients with AL (52.2%). In MMP2 positive and
      negative groups of AL, the extramedullary infiltration rates were 50.0% and 18.2%
      (P < 0.05), whilst the percentage of blast cell in peripheral white blood cells
      were (77.21 +/- 13.9)% and (62.95 +/- 17.2)% (P < 0.01), respectively. The
      positive expression of TIMP2 and MT1-MMP in 46 AL patients were 27 (58.7%) and 33
      (71.7)%. The matrigel invasion assay suggested that MMP2 is involved in migration
      of leukemic cell through extracellular matrix (Matrigel). CONCLUSION: The active
      form of MMP2 might be essential to the egress of leukemic cells from bone marrow
      into peripheral blood, followed by an extramedullary infiltration.

PMID- 14633461
TI  - [The expression of DNA methyltransferase DNMT1, 3A and 3B in acute leukemia and
      myelodysplastic syndrome].
AB  - OBJECTIVE: To explore the relationship between methyltransferases and the
      pathogenesis of acute leukemia (AL) and the leukemic transformation of
      myelodysplastic syndromes (MDS). METHODS: Semi-quantitative RT-PCR method was
      used to detect the mRNA expression level of DNMT1, 3A and 3B in bone marrow cells
      from 75 patients with AL or MDS. RESULTS: There was no significant difference in
      mRNA expression level of DNMTs between a low-risk MDS group (n = 21) and a normal
      group. However, increased expression level of DNMT1, 3A and 3B was found in
      47.6%, 47.6% and 42.9% of the patients in the low-risk group, respectively, if
      the upper limit of 80% of the normal controls was considered as the critical
      level. In high-risk MDS (n = 13), a more proportion of the cases with increased
      expression level of DNMTs were found, that was 53.8%, 76.9% and 92.3%
      respectively, and only expression level of DNMT3B was significantly higher than
      that in the low-risk MDS group (P < 0.01). In the AL group (n = 41) expression
      level of all the three subtypes was coordinately higher than that in the MDS
      group (P < 0.01), companying with a more frequency of 92.7%, 97.6% and 100%.
      Comparing with the AML group, a significantly increased expression level of DNMT1
      (P < 0.01) with the same level of DNMT 3A and 3B was interestingly observed in
      the ALL group. CONCLUSIONS: It is possible that up-regulated DNMTs contribute to
      the pathogenesis of AL and the leukemic transformation of MDS, and DNMT3B might
      be the most important enzyme among the three subtypes.

PMID- 14633462
TI  - [Molecular genetic analysis for a pedigree with severe hereditary coagulation
      factor VII deficiency].
AB  - OBJECTIVE: To identify the genetic mutations of a severe inherited coagulation
      factor VII (FVII) deficiency pedigree. METHODS: The diagnosis was validated by
      coagulant and haemostatic parameters. FVII gene mutations were screened in the
      propositus and his family members by DNA direct sequencing and confirmed by
      digestions of the restriction enzymes of the PCR production. RESULTS: Two
      heterozygous missense mutations were found in the propositus of the pedigree: a G
      to T transversion at position 9482 in exon 6 and a C to T mutation at position
      11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and
      Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at
      position 11487-11489(CCC) within exon 8 was identified, which predicted the
      frameshift mutation at position His351 followed by the changes of six
      corresponding amino acids and appearance of a premature protein caused by stop
      codon. The heterozygous mutations identified in the proband were derived from his
      father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous
      deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it
      was found that his grandmother had a heterozygous mutation of Arg304Trp and a
      heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous
      Arg152Leu mutation. CONCLUSION: Three heterozygous mutations were found in a
      pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and
      deletion C at position 11487-9(CCC) were novel mutations.

PMID- 14633463
TI  - [The clinical characteristics of acute coronary syndrome in China].
AB  - OBJECTIVE: To analyse the characteristics of and the therapeutic measures for
      patients with acute ischemic syndromes in China. METHOD: This study is a part of
      an international multicentre registry-the Organization to Assess Strategies for
      Ischemic Syndromes (OASIS). Since April 1999, the data of patients admitted to
      hospital with acute ischemic cardiac chest pain have been collected by filling
      Case Report Forms offered by the Canadian Cardiovascular Collaboration. The main
      clinical characteristics of the patients and in hospital events were recorded.
      RESULTS: Two thousand two hundred and ninety cases of acute ischemic syndromes
      from 38 hospitals throughout the nation were enrolled in the registry (include
      unstable angina and non Q-wave myocardial infarction). The mean age of the
      patients was 62.8. The percentage of patients with chest pain at presentation and
      abnormal ECG was 48.9% and 89.7%, respectively. The clinical diagnosis at
      admission was unstable angina (UA) in 90.9% of the patients and non Q-wave
      myocardial infarction (non Q-wave MI) in the remaining 9.0%. During
      hospitalization the intervention procedures performed were as follows:
      thrombolytic therapy (TT) in 75 cases (3.3%), coronary angiography (CA) in 798
      cases (34.9%), percutaneous transluminal coronary angioplasty (PTCA) in 403 cases
      (17.6%) and coronary artery bypass graft surgery (CABG) in 97 cases (4.2%).
      Nitrates (oral or patch) and anti platelet therapy were used in 2 212 cases
      (96.6%) and 2 163 cases (94.5%), respectively. The incidence of major in hospital
      events was 15.2%, including 31 deaths (1.4%). CONCLUSION: The patients with acute
      ischemic syndromes were diagnosed as unstable angina mostly in China. A
      relatively high PTCA rate but low CABG rate were noted in China. The most common
      cause of in hospital death is severe arrhythmias or sudden death.

PMID- 14633464
TI  - [Cyclooxygenase-2 expression in esophageal cancer cells and induction by
      mitomycin C].
AB  - OBJECTIVE: To study the relationship between COX-2 expression in esophageal
      cancer cell (EC/CUHK-1) and mitomycin C (MMC) treatment. METHODS: 2 mg/L of MMC
      was added to the well-grown EC/CUHK-1 cells cultured in RPMI-1640 including 10%
      FCS, and the medium was totally changed after 0.5, 1, 2, 4 and 8 h treatment,
      respectively. Cells were collected after another 24 h culture. Protein expression
      of COX-2, Bcl-2, Rb, p53 were examined by Western blot, and RT-PCR method was
      used to confirm the COX-2 expression in mRNA level. Cell cycle analysis for cells
      collected at 0, 0.5, 2, 4 and 8 h was performed on an EPICS profile analyzer.
      RESULTS: The cell cycle analysis showed that the percentage of apoptosis cells
      were (4.12 +/- 0.83)%, (1.00 +/- 0.11)%, (4.32 +/- 0.99)%, (9.46 +/- 2.11)% and
      (31.10 +/- 3.57)%, respectively. COX-2 mRNA expression were 2.60, 1.70, and 0.08
      times, COX-2 protein expression were 2.0, 3.1 and 2.8 times, Bcl-2 protein were
      3.6, 14.0 and 12.0 times, p53 protein were 1.8, 0.5 and 0.2 times,
      hyperphosphorylated form Rb were 8.2, 8.4 and 6.2 times, underphosphorylated form
      Rb were 1.8, 0.5 and 0.2 times in 0.5, 2 and 4 h after MMC treatment,
      respectively, as compared with the control group. CONCLUSIONS: The COX-2
      expression showed coincidence up-regulation according to the MMC-induced anti
      apoptosis function activation in esophageal cancer cells, and the process was at
      least partly associated with Rb phosphorylation and p53 accumulation. It is
      implied that COX-2 may be a protecting factor in MMC induced esophageal cancer
      cell apoptosis, and the use of COX-2 inhibitor as an enhancer for esophageal
      cancer chemotherapy may be reasonable.

PMID- 14633465
TI  - [Effect of mild and moderate excessive iodine supplementation on thyroid function
      and morphology in non-iodine deficiency rat model].
AB  - OBJECTIVE: To study the effect of moderate and mild iodine excess on thyroid
      function and morphology in non iodine deficiency Wistar rats. METHODS: Serum
      thyroid-stimulating hormone (TSH) was measured with solid phase radioimmunoassay
      (IRMA) and serum total T(4) (TT(4)), TT(3), reverse T(3) (rT(3)) and thyroid
      TT(4) with radioimmunoassay (RIA). Cer-Arsenite colorimetric method was used to
      measure median urinary iodine (MUI). Thyroid morphological changes were observed
      under optical and electronic microscope. Metamorphic imaging system was used to
      measure the height of thyrocytes and the areas of thyroid follicular cavities.
      RESULTS: Iodine intake of three times than normal for 90 days could increase
      serum TSH but without significant difference; Serum TT(3) values were markedly
      lower than those in control, P = 0.0001. Serum and thyroid TT(4) values were
      markedly higher than those in double distilled water (DDW) group, P value being
      0.001 and 0.0001 respectively. However, serum rT(3) did not change markedly when
      compared with that in DDW group. The area of follicular cavity increased,
      follicular cells became flat, nucleus stained darker, follicles broke and
      combined, giant follicles were formed, and the capillaries around the follicules
      were reduced. The height of thyrocytes was markedly lower than those in DDW
      group, while the areas of thyroid follicular cavities were markedly larger than
      those in DDW group (both P values were 0.001). Thyroid ultrastructure showed
      enlargement of endoplasmic reticulum of thyroid follicular cells, increase of
      number of secondary lysosomes, darker stain of nuclei, condensation of chromatin
      and reduction of microvilli. CONCLUSION: Iodine intake over 3 times than normal
      may potentiate the possibility of hypothyroidism and inhibit the function of most
      of thyrocytes in non iodine deficiency rats.

PMID- 14633466
TI  - [Role of single-breath carbon monoxide-diffusing capacity in monitoring the
      bleomycin-induced lung toxicity in human].
AB  - OBJECTIVE: To investigate if the carbon monoxide-diffusing capacity (D(LCO))
      could be the early indictor monitoring the bleomycin-induced lung toxicity (BILT)
      with retrospection of the influence of bleomycin cumulative dose on the pulmonary
      functions. METHODS: During June 1985 to October 2000, 42 patients with malignant
      tumor of ovarian germ cells received chemotherapy containing bleomycin in the
      department of Obstetrics and Gynecology of Peking Union Medical College Hospital.
      Twenty three patients (54.76%) among them had >or= 2 courses of chemotherapy with
      bleomycin and performed >or= 2 measurements of lung function. These 23 patients
      were included in the study. The forced expiratory volume in one second (FEV(1)),
      forced vital capacity (FVC), total lung capacity (TLC) and D(LCO) were measured
      and recorded as % of predicted. The D(LCO) was corrected by hemoglobin
      concentration [D(LCO) corrected = D(LCO) measured x (9.38 + Hb) divided by (1.76
      x Hb)]. All the data were divided into 4 groups according to the cumulative dose
      of bleomycin (pre-treatment group, < 100 mg group, 101 - 200 mg group and > 201
      mg group). The relationship between D(LCO) and bleomycin cumulative dose was
      examined by linear regression analysis and t-test. RESULTS: The values of
      FEV(1%)predicted in the 4 groups were 99.83 +/- 16.41 (14), 101.43 +/- 12.32
      (42), 99.41 +/- 10.22 (23), and 90.96 +/- 13.63 (12), respectively. The
      FVC%predicted were 97.74 +/- 18.23 (14), 101.11 +/- 13.95 (42), 96.49 +/- 12.04
      (23) and 89.63 +/- 18.20 (12), respectively. The TLC%predicted were 101.22 +/-
      10.68 (13), 106.14 +/- 12.16 (40), 102.13 +/- 11.33 (23) and 95.05 +/- 14.06
      (11), respectively. There were no statistical significant differences in the
      parameters among the 4 groups. The D(LCO%)predicted of the 4 groups were 93.27 +/
      12.75 (14), 94.51 +/- 12.50 (40), 80.93 +/- 10.05 (24) and 70.99 +/- 11.69 (15),
      respectively, and the D(LCO) of the last group (> 201 mg group) was significantly
      decreased as compared to that of the other groups (P < 0.05). A bleomycin dose
      related fall in D(LCO) was observed, y = 100.59 - 0.11x, r = -0.649, P < 0.001.
      CONCLUSION: The D(LCO) might be the most sensitive indicator of subclinical BILT.
      However, the cumulative dose of bleomycin did not show significant influence on
      the FEV(1), FVC and TLC.

PMID- 14633467
TI  - Trends in the social psychological study of justice.
AB  - Justice is one of the most basic and potentially important social psychological
      areas of inquiry. The assumption that others will be fair is what makes social
      cooperation possible. This article provides a brief review of trends, both
      historical and current, in the social psychological study of justice, and
      provides an introduction for a special issue of Personality and Social Psychology
      Review devoted to social psychological theorizing and research on the role that
      justice plays in human affairs. This overview highlights some exciting new
      directions in justice theorizing and research, including new uses of identity's
      ties to justice reasoning, increased attention to negative justice and moral
      emotion, as well as a greater emphasis on integrative and contingent, rather than
      competing, social psychological models of justice.

PMID- 14633468
TI  - Of different minds: an accessible identity model of justice reasoning.
AB  - An accessible identity model (AIM) of justice reasoning is introduced to explain
      when people become concerned about justice and how they define what is fair or
      unfair once justice concerns are activated. This model has two core propositions:
      (a) People are most likely to think about justice and fairness when self-relevant
      values and goals are highly accessible or activated, and (b) how people define
      fairness depends on which aspect of the self (i.e., material, social, or personal
      and moral) dominates the working self-concept. A review of the literature
      indicates that this general model provides an integrative account for when and
      how people become concerned about both procedural and distributive justice, and
      provides a cogent explanation for known effects and results previously thought to
      be anomalies. Finally, the model generates novel hypotheses about how identity
      threat may lead to motivated perceptions of fairness or unfairness.

PMID- 14633469
TI  - Justice and identity: changing perspectives on what is fair.
AB  - Most research on justice has aimed to describe abstract, depersonalized models
      that could apply to anyone. However, much of this research has involved identity,
      if only implicitly. We argue that justice needs to be contextualized to take into
      account the powerful effects of identity in determining when justice matters. The
      complexity and fluidity of identity need to be considered to understand when,
      why, and how strongly people care about justice, and how people choose among
      competing models of justice. We review existing research on distributive,
      procedural, and inclusionary justice and describe their connection to identity.
      We illustrate the intersection of justice and identity in environmental issues, a
      context in which these constructs have significant implications for individual,
      community, and planetary well-being. We conclude with 4 points to stimulate
      further research on the intersections of identity and justice.

PMID- 14633470
TI  - Forgiveness and justice: a research agenda for social and personality psychology.
AB  - Forgiveness and related constructs (e.g., repentance, mercy, reconciliation) are
      ripe for study by social and personality psychologists, including those
      interested in justice. Current trends in social science, law, management,
      philosophy, and theology suggest a need to expand existing justice frameworks to
      incorporate alternatives or complements to retribution, including forgiveness and
      related processes. In this article, we raise five challenging empirical questions
      about forgiveness. For each question, we briefly review representative research,
      raise hypotheses, and suggest specific ways in which social and personality
      psychologists could make distinctive contributions.

PMID- 14633471
TI  - The group engagement model: procedural justice, social identity, and cooperative
      behavior.
AB  - The group engagement model expands the insights of the group-value model of
      procedural justice and the relational model of authority into an explanation for
      why procedural justice shapes cooperation in groups, organizations, and
      societies. It hypothesizes that procedures are important because they shape
      people's social identity within groups, and social identity in turn influences
      attitudes, values, and behaviors. The model further hypothesizes that resource
      judgments exercise their influence indirectly by shaping social identity. This
      social identity mediation hypothesis explains why people focus on procedural
      justice, and in particular on procedural elements related to the quality of their
      interpersonal treatment, because those elements carry the most social identity
      relevant information. In this article, we review several key insights of the
      group engagement model, relate these insights to important trends in
      psychological research on justice, and discuss implications of the model for the
      future of procedural justice research.

PMID- 14633472
TI  - Connections between the ivory tower and the multicolored world: linking abstract
      theories of social justice to the rough and tumble of affirmative action.
AB  - This article seeks to combine the social psychologist's interest in articulating
      and testing concepts with the public policymaker's interest in the effective
      implementation of specific policies and programs. The first part of the article
      applies knowledge about distributive and procedural justice to understanding some
      of the opposition to affirmative action. The application also reveals some
      lacunae-specifically concerning rule change-in how social psychologists have
      looked at procedural justice issues. In the second part of the article, we
      discuss the problem of rule change and propose a set of conceptualizations about
      the conditions that govern people's reactions to rule change. We end by
      reflecting on some changes in our studies of procedural justice.

PMID- 14633473
TI  - Justice within social dilemmas.
AB  - The defining feature of social dilemma situations is the inherent conflict faced
      by those involved: should one act in his or her own individual best interest or
      sacrifice a measure of one's personal payoff to help maximize the joint payoff of
      the group as a whole? In such dilemmas, those making individualistic and
      defecting choices are always at a competitive advantage relative to those who
      choose to cooperate. One seemingly inevitable consequence of the resulting
      resource allocation asymmetry is that it must challenge and threaten the
      cooperator's sense of fairness and justice, and it is the reaction of those
      caught in social dilemmas to this injustice and unfairness that is the focus of
      this article. We examine how justice processes-distributive justice, procedural
      justice, restorative justice, and retributive justice-operate in social dilemmas.
      Within this examination, we consider ideas from classic and contemporary
      conceptual analyses of justice to provide a broader context within which to
      understand social dilemmas and the roles that justice plays as people strive to
      ensure fair outcomes for themselves and for others. We conclude with the proposal
      of a 4-stage, sequential model of justice in social dilemmas that posits groups
      move between the types of justice concerns when unfair and unsatisfactory
      outcomes (e.g., inequitable resource allocations, violations of agreed-on
      allocation rules, intentional and egregious exploitation of the group) cause
      members to "recognize the necessity" for change to ensure fair and just outcomes
      for all.

PMID- 14633474
TI  - The justice motive: where social psychologists found it, how they lost it, and
      why they may not find it again.
AB  - Beginning shortly after the 2nd World War, 3 lines of research associated with
      relative deprivation, equity theory, and just world contributed to the
      description of the influence of the justice motive in people's lives. By the late
      1960s, these converging lines of research had documented the importance of
      people's desire for justice; nevertheless, contemporary social psychologists
      typically portray this justice-driven motivation as simply a manifestation of
      self-interest. The explanation for this failure to recognize a distinct and
      important justice motive points to the widespread reliance on research methods
      that elicit the participant's thoughtfully constructed narratives or role-playing
      responses. According to recent theoretical advances, these methods generate
      responses that reflect normative expectations of rational self-interest, and fail
      to capture the important effects of the emotionally generated imperatives of the
      justice motive.

PMID- 14633476
TI  - Is carb-cutting a safe way to diet? New research suggests that a high-protein,
      low-carbohydrate diet is less risky than many experts had thought. Does that mean
      it's a healthy way to eat?

PMID- 14633477
TI  - Postmenopausal hormones. Hormone therapy: what happened? Our assumptions about
      taking hormones after menopause have mostly been dashed. How did we get it so
      wrong?

PMID- 14633478
TI  - Asthma in older women. Asthma affects our lungs the same way at all ages, but the
      intricacies of prevention and treatment change as we get older.

PMID- 14633479
TI  - Fitness and health. Benefits of moderate activity confirmed.

PMID- 14633480
TI  - By the way, doctor. What causes fingernails to split and break, and what can be
      done about it?

PMID- 14633481
TI  - By the way, doctor. A new television ad says I should ask my doctor about Plavix,
      a drug that reduces the risk of heart attack and stroke. I'm 65 years old and
      healthy. Should I be taking Plavix preventively?

PMID- 14633483
TI  - Social anxiety disorder.

PMID- 14633482
TI  - Preventing strokes: a plan of action.

PMID- 14633484
TI  - Medical memo. Y are we men?

PMID- 14633485
TI  - On call. My brother takes Chinese herbs to boost his energy, and he swears by
      them. He gave me some tablets, but I haven't taken them yet. I know his
      enthusiasm may be psychological, but I'd like to try them anyway if you say they
      are safe.

PMID- 14633486
TI  - Alzheimer's disease: a progress report. How far the search for treatments has
      come and where it is heading.

PMID- 14633487
TI  - After the trauma: what doesn't help and what may.

PMID- 14633488
TI  - A drug treatment for alcoholism.

PMID- 14633489
TI  - Depression under stress: the long and short of it.

PMID- 14633490
TI  - Homosexuality and injury to self.

PMID- 14633491
TI  - Borderline prognosis.

PMID- 14633492
TI  - Questions & answers. I've read that antidepressants are now officially
      recommended as the best drug treatment for panic disorder. Are the benzodiazepine
      anti-anxiety drugs still regarded as useful?

PMID- 14633493
TI  - The 'precursor' syndrome. Catch a problem early and you prevent serious illness
      and suffering. But are we creating a bonanza for the pharmaceutical industry in
      the process?

PMID- 14633494
TI  - The big chill: Raynaud's phenomenon. Having cold hands is common--Raynaud's
      phenomenon is not. Bundling up helps both.

PMID- 14633495
TI  - Preventing delirium in the hospital. Sometimes is can't be avoided. But small
      things like making sure someone wears her glasses may help.

PMID- 14633496
TI  - Sizing up South Beach. It makes some good points, but The South Beach Diet has
      problems typical of diet books: lack of proof and some dubious claims.

PMID- 14633498
TI  - Less food for thought.

PMID- 14633497
TI  - Are you wary of herbal medicines? Join the crowd. Some figures show sales are
      down. Consumers need quality products and credible research.

PMID- 14633499
TI  - Flu vaccine: through the nose, not the needle.

PMID- 14633500
TI  - Heart attack prevention: trust the old reliables.

PMID- 14633501
TI  - By the way, Doctor. I'm a 52-year-old tennis player who needs a hip replacement.
      The orthopedists in my area do a metal-ball-in-polyethylene-cup replacement that
      I'm told lasts 10-15 years. But I've heard that metal-ball-in-metal-cup
      replacements last longer. What do you think?

PMID- 14633502
TI  - By the way, doctor. I read in your July 2003 article on the new blood pressure
      guidelines with interest because I have high blood pressure. But one thing
      bothers me about articles on blood pressure: they always seem to talk about blood
      pressure as if it were the same number all day long. In my case, the systolic
      pressure can vary by 30 points and the diastolic by 15. So which should you use
      as your blood pressure reading: the average, the highest, or the lowest?

PMID- 14633503
TI  - Major risk. Most people with heart disease have one or more of the Big Four risk
      factors.

PMID- 14633504
TI  - Tricky forecast: Low pressure. Deep dips in blood pressure upon standing or after
      eating can cause dizziness, fainting, and falls. Here's how to cope with the
      problem.

PMID- 14633505
TI  - Seek out over-the-counter drug information. To get the most out of the drugs you
      need to take each day, try working with an expert--your pharmacist.

PMID- 14633506
TI  - Pay attention to potassium. Getting more of this essential mineral, or holding
      onto what you have, helps the heart and blood vessels.

PMID- 14633507
TI  - Valve job. When the aortic valve fails, surgery is the only option. Prevention,
      once thought impossible, could help you avoid this major operation.

PMID- 14633508
TI  - Don't let fear of fats trump the power of produce.

PMID- 14633509
TI  - Ask the doctor. I read somewhere that cocoa butter doesn't raise cholesterol
      levels even though it contains a lot of saturated fat. If this is true, can I eat
      dark chocolate without worrying about what it's doing to my heart and blood
      vessels?

PMID- 14633510
TI  - Ask the doctor. Even though my weight and health are fine (good blood pressure
      and cholesterol), my doctor and my partner want me to be more active. But I don't
      like exercise, and I've heard of people dying while they exercise. Why should I
      bother doing something that isn't totally safe?

PMID- 14633511
TI  - Vascular endothelial growth factor-induced secretion of fibronectin is ERK
      dependent.
AB  - In severe asthma, cytokines and growth factors contribute to the proliferation of
      smooth muscle cells and blood vessels, and to the increased extracellular matrix
      deposition that constitutes the process of airway remodeling. Vascular
      endothelial growth factor (VEGF), which regulates vascular permeability and
      angiogenesis, also modulates the function of nonendothelial cell types. In this
      study, we demonstrate that VEGF induces fibronectin secretion by human airway
      smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates
      ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK
      activation and fibronectin secretion appear to be mediated through the VEGF
      receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta
      growth factor. Finally, we demonstrate that ASM cells constitutively secrete
      VEGF, which is increased in response to PDGF, transforming growth factor-beta, IL
      1beta, and PGE(2). We conclude that ASM-derived VEGF, through modulation of the
      extracellular matrix, may play an important role in airway remodeling seen in
      asthma.

PMID- 14633512
TI  - Glucocorticoid inhibition of SP-A gene expression in lung type II cells is
      mediated via the TTF-1-binding element.
AB  - Induction of surfactant protein-A (SP-A) gene expression in fetal lung type II
      cells by cAMP and IL-1 is mediated by increased binding of thyroid transcription
      factor-1 (TTF-1) and NF-B proteins p50 and p65 to the TTF-1-binding element (TBE)
      at -183 bp. In type II cell transfections, dexamethasone (Dex) markedly inhibits
      cAMP-induced expression of rabbit SP-A:human growth hormone (hGH) fusion genes
      containing as little as 300 bp of the SP-A 5'-flanking sequence. Dex inhibition
      is blocked by RU-486, suggesting a role of the glucocorticoid receptor (GR). The
      present study was undertaken to define the mechanisms for GR inhibition of SP-A
      expression. Cotransfection of primary cultures of type II cells with a GR
      expression vector abrogated cAMP induction of SP-A promoter activity while, at
      the same time, causing a 60-fold induction of cotransfected mouse mammary tumor
      virus (MMTV) promoter. In lung cells transfected with a fusion gene containing
      three TBEs fused to the basal SP-A promoter, Dex prevented the stimulatory effect
      of IL-1 on TTF-1 induction of SP-A promoter activity, suggesting that the GR
      inhibits SP-A promoter activity through the TBE. In gel shift assays using
      nuclear extracts from human fetal type II cells cultured in the absence or
      presence of cAMP, Dex markedly reduced binding of nuclear proteins to the TBE and
      blocked the stimulatory effect of cAMP on TBE-binding activity. Our finding that
      Dex increased expression of the NF-kappaB inhibitory partner IkappaB-alpha
      suggests that the decrease in TBE-binding activity may be caused, in part, by GR
      inhibition of NF-kappaB interaction with this site.

PMID- 14633513
TI  - Altered expression and in vivo lung function of protease-activated receptors
      during influenza A virus infection in mice.
AB  - Protease-activated receptors (PARs) are widely distributed in human airways, and
      recent evidence indicates a role for PARs in the pathophysiology of inflammatory
      airway disease. To further investigate the role of PARs in airway disease, we
      determined the expression and function of PARs in a murine model of respiratory
      tract viral infection. PAR-1, PAR-2, PAR-3, and PAR-4 mRNA and protein were
      expressed in murine airways, and confocal microscopy revealed colocalization of
      PAR-2 and cyclooxygenase (COX)-2 immunostaining in basal tracheal epithelial
      cells. Elevated levels of PAR immunostaining, which was particularly striking for
      PAR-1 and PAR-2, were observed in the airways of influenza A/PR-8/34 virus
      infected mice compared with sham-infected mice. Furthermore, increased PAR-1 and
      PAR-2 expression was associated with significant changes in in vivo lung function
      responses. PAR-1 agonist peptide potentiated methacholine-induced increases in
      airway resistance in anesthetized sham-infected mice (and in indomethacin
      treated, virus-infected mice), but no such potentiation was observed in virus
      infected mice. PAR-2 agonist peptide transiently inhibited methacholine-induced
      bronchoconstriction in sham-infected mice, and this effect was prolonged in virus
      infected mice. These findings suggest that during viral infection, the
      upregulation of PARs in the airways is coupled to increased activation of COX and
      enhanced generation of bronchodilatory prostanoids.

PMID- 14633514
TI  - Enhancement of the endotoxin recognition pathway by ventilation with a large
      tidal volume in rabbits.
AB  - Ventilation with a small tidal volume (V(t)) is associated with better clinical
      outcomes than with a large V(t), particularly in critical settings, including
      acute lung injury. To determine whether V(t) influences the lipopolysaccaharide
      (LPS) recognition pathway, we studied CD14 expression in rabbit lungs and the
      release of TNF-alpha by cultured alveolar macrophages after 240 min of
      ventilation with a large (20 ml/kg) vs. a small (5 ml/kg) V(t). We also applied
      small or large V(t) to lungs instilled with 50 microg/kg of LPS. The alveolar
      macrophages collected after large V(t) ventilation revealed a 20-fold increase in
      LPS-induced TNF-alpha release compared with those collected after small V(t)
      ventilation, whereas TNF-alpha was undetectable without LPS stimulation. In
      animals ventilated with a large V(t), the expression of CD14 mRNA in whole lung
      homogenates and the expression of CD14 protein on alveolar macrophages, assessed
      by immunohistochemistry, were both significantly increased in the absence of LPS
      stimulation. A large V(t) applied to LPS-instilled lungs increased the pulmonary
      albumin permeability and TNF-alpha release into the plasma. These results suggest
      that mechanical stress caused by a large V(t) sensitizes the lungs to endotoxin,
      a phenomenon that may occur partially via the upregulation of CD14.

PMID- 14633515
TI  - TRPV1 receptors mediate particulate matter-induced apoptosis.
AB  - Exposure to airborne particulate matter (PM) is a world-wide health problem
      mainly because it produces adverse cardiovascular and respiratory effects that
      frequently result in morbidity. Despite many years of epidemiological and basic
      research, the mechanisms underlying PM toxicity remain largely unknown. To
      understand some of these mechanisms, we measured PM-induced apoptosis and
      necrosis in normal human airway epithelial cells and sensory neurons from both
      wild-type mice and mice lacking TRPV1 receptors using Alexa Fluor 488-conjugated
      annexin V and propidium iodide labeling, respectively. Exposure of environmental
      PMs containing residual oil fly ash and ash from Mount St. Helens was found to
      induce apoptosis, but not necrosis, as a consequence of sustained calcium influx
      through TRPV1 receptors. Apoptosis was completely prevented by inhibiting TRPV1
      receptors with capsazepine or by removing extracellular calcium or in sensory
      neurons from TRPV1(-/-) mice. Binding of either one of the PMs to the cell
      membrane induced a capsazepine-sensitive increase in cAMP. PM-induced apoptosis
      was augmented upon the inhibition of PKA. PKA inhibition on its own also induced
      apoptosis, thereby suggesting that this pathway may be endogenously protective
      against apoptosis. In summary, it was found that inhibiting TRPV1 receptors
      prevents PM-induced apoptosis, thereby providing a potential mechanism to reduce
      their toxicity.

PMID- 14633516
TI  - Mucociliary transport determined by in vivo microdialysis in the airways of
      normal and CF mice.
AB  - We report a novel method to measure mucociliary transport (MCT) in both the upper
      and lower airways of normal and CF mice. The in vivo microdialysis technique
      involves placing a small quantity of dye on the airway surface and a
      microdialysis probe a defined distance from the site of dye deposition. The dye
      is transported toward the probe by ciliary transport and, upon reaching the
      microdialysis probe, diffuses across the dialysis membrane and is collected in
      the dialysate leaving the probe. The rate of MCT is calculated from the length of
      time from dye deposition to recovery. The rate of tracheal MCT in normal mice was
      2.2 +/- 0.45 (SE) mm/min (n = 6), a value similar to that in reports using other
      techniques. MCT in CF mice was not different (2.3 +/- 0.29, n = 6), consistent
      with previous observations suggesting that tracheal ion transport properties are
      not different between CF and normal mice. The rate of MCT in the nasal cavity of
      normal mice was slower than in the trachea (1.3 +/- 0.26, n = 4). MCT in the CF
      mouse nasal cavity (1.4 +/- 0.31, n = 8), a region in which the CF mouse exhibits
      bioelectric properties similar to the human CF patient, was, again, not different
      from the normal mouse, perhaps reflecting copious gland secretion offsetting
      Na(+) and liquid hyperabsorption. In conclusion, we have developed a versatile,
      simple in vivo method to measure MCT in both upper and lower airways of mice and
      larger animals.

PMID- 14633517
TI  - Acute lung injury after pulmonary resection: more pieces of the puzzle.

PMID- 14633519
TI  - Risk factors for acute lung injury after thoracic surgery for lung cancer.
AB  - Acute lung injury (ALI) may complicate thoracic surgery and is a major
      contributor to postoperative mortality. We analyzed risk factors for ALI in a
      cohort of 879 consecutive patients who underwent pulmonary resections for non
      small cell lung carcinoma. Clinical, anesthetic, surgical, radiological,
      biochemical, and histopathologic data were prospectively collected. The total
      incidence of ALI was 4.2% (n = 37). In 10 cases, intercurrent complications
      (bronchopneumonia, n = 5; bronchopulmonary fistula, n = 2; gastric aspiration, n
      = 2; thromboembolism, n = 1) triggered the onset of ALI 3 to 12 days after
      surgery, and this was associated with a 60% mortality rate (secondary ALI). In
      the remaining 27 patients, no clinical adverse event preceded the development of
      ALI-0 to 3 days after surgery-that was associated with a 26% mortality rate
      (primary ALI). Four independent risk factors for primary ALI were identified:
      high intraoperative ventilatory pressure index (odds ratio, 3.5; 95% confidence
      interval, 1.7-8.4), excessive fluid infusion (odds ratio, 2.9; 95% confidence
      interval, 1.9-7.4), pneumonectomy (odds ratio, 2.8; 95% confidence interval, 1.4
      6.3), and preoperative alcohol abuse (odds ratio, 1.9; 95% confidence interval,
      1.1-4.6). In conclusion, we describe two clinical forms of post-thoracotomy ALI:
      1). delayed-onset ALI triggered by intercurrent complications and 2). an early
      form of ALI amenable to risk-reducing strategies, including preoperative alcohol
      abstinence, lung-protective ventilatory modes, and limited fluid intake.
      IMPLICATIONS: In an observational study including all patients undergoing lung
      surgery, we describe two clinical forms of acute lung injury (ALI): a delayed
      onset form triggered by intercurrent complications and an early form associated
      with preoperative alcohol consumption, pneumonectomy, high intraoperative
      pressure index, and excessive fluid intake over the first 24 h.

PMID- 14633520
TI  - The importance of intraoperative transesophageal echocardiography in endovascular
      repair of thoracic aortic aneurysms.
AB  - Endovascular repair of the aorta (EVAR) is a promising alternative to open
      repair. Transesophageal echocardiography (TEE) is a sensitive imaging modality
      for aortic disease. We reviewed our experience with TEE in thoracic EVAR. Seven
      patients underwent thoracic EVAR under general anesthesia. Intraoperative
      angiography and TEE were used to identify the extent of the aneurysm and guide
      placement of the stent. Doppler color flow was used to supplement angiography to
      detect flow within the aneurysmal sac after stent placement. The endograft was
      successfully deployed in six patients. Endoleak was identified by TEE in three
      patients and confirmed by angiography in two of them. EVAR was abandoned in one
      patient on the basis of TEE findings of extensive aortic dissection. We found TEE
      to be a valuable intraoperative tool for 1) identifying aortic pathology, 2)
      confirming that the guidewire is in the true lumen, 3) aiding stent graft
      positioning, and 4) supplementing angiography for detecting endoleaks. TEE can
      supplement information obtained by angiography to enhance the accuracy of EVAR
      and potentially improve outcomes. The anesthesiologist is ideally positioned to
      provide the endovascular team with vital information regarding stent positioning,
      endoleaks, and cardiac performance with a single imaging modality. IMPLICATIONS:
      Endovascular repair is an emerging alternative to open surgery for aortic
      aneurysms. We found transesophageal echocardiography to be a valuable imaging
      tool for guiding placement of the endograft, detecting leaks around the
      endograft, and supplementing information derived from angiography during
      endograft deployment.

PMID- 14633521
TI  - The effects of desflurane and propofol on portosystemic pressure in patients with
      portal hypertension.
AB  - Physicians perform hepatic venous pressure measurements to guide medical therapy
      aimed at reducing portal hypertension. These measurements are frequently
      performed during general anesthesia. Since most general anesthetic drugs reduce
      liver blood flow, it is likely that hepatic venous pressures will be altered. We
      therefore examined the effects of two frequently used anesthetic drugs on hepatic
      venous pressure in a prospective randomized study to determine if pressure
      measurements taken during general anesthesia were similar to awake values. We
      studied 21 patients with hepatitis C, excluding patients with hepatofugal flow
      and portal vein thrombosis. All patients had free and wedged hepatic venous
      pressures measured awake with sedation and after anesthesia with either propofol
      or desflurane. Desflurane significantly increased free hepatic venous pressure
      (11.9 +/- 4.4 to 23.5 +/- 4.1 mm Hg; P < 0.05) and decreased hepatic venous
      pressure gradient (21.6 +/- 7.4 to 14.7 +/- 5.2 mm Hg; P < 0.05), whereas
      propofol did not change these variables. We conclude that desflurane, but not
      propofol, alters hepatic venous pressure measurements from the awake state,
      significantly increasing free hepatic venous pressure and decreasing the hepatic
      venous pressure gradient, an indirect measure of portosystemic pressure. Changes
      in the hepatic venous pressure gradient must be interpreted with caution during
      desflurane general anesthesia. IMPLICATIONS: Desflurane reduces the blood
      pressure difference between the portal and systemic circulations. This can cause
      errors in assessment of the success of medical therapy of portal hypertension.
      Propofol has less effect on the difference between the portal and systemic
      circulation.

PMID- 14633523
TI  - A comparison of red cell recovery between two different methods of red cell
      washing.
AB  - The success of cell salvage varies depending upon how many shed red blood cells
      (RBC) are captured from the surgical wound and returned to the patient. Here, the
      authors hypothesized that pneumatic disk (PD) processing might provide better RBC
      recovery when compared with traditional Latham bowl (LB) techniques. Comparison
      of the speed of processing, product hemoglobin and salvage efficiency was made
      between the two machines when their reservoirs were loaded with blood volumes
      ranging from 100 mL to 1000 mL. The PD provided a consistent hemoglobin
      concentration (21.7 +/- 0.8 g/dL; mean +/- SD), whereas the LB provided varying
      hemoglobin concentrations dependent upon the starting volume (range, 2.9 +/- 0.7
      g/dL to 18.4 +/- 0.8 g/dL). The PD also provided more efficiency versus full LB
      only (79.4% versus 56.3%; P = 0.001). When all RBCs were processed, the LB
      technology provided statistically larger degrees of RBC return (79.4% versus
      83.6% for the PD versus LB, respectively; P < 0.001). The processing speed of the
      LB was faster at all starting volumes. In conclusion, for small volumes of blood
      loss where a full LB is not achieved, the PD will return a larger number of cells
      with a more consistent hemoglobin per volume of blood processed. IMPLICATIONS:
      This study compared two types of cell salvage equipment. Pneumatic disk
      processing may offer advantages over traditional devices when small blood loss is
      anticipated.

PMID- 14633524
TI  - Kidney-specific proteins in elderly patients undergoing cardiac surgery with
      cardiopulmonary bypass.
AB  - In cardiac surgery, acute renal failure (ARF) is more likely in elderly patients
      than in younger patients. We assessed whether kidney function is different
      between elderly and younger cardiac surgery patients by measuring kidney-specific
      proteins. Forty consecutive patients aged <60 yr and 40 patients aged >70 yr
      without preoperative kidney dysfunction undergoing elective cardiac surgery with
      cardiopulmonary bypass (CPB) were included. Creatinine clearance and fractional
      excretion of sodium, as well as urine concentrations of N-acetyl-beta-D
      glucosaminidase, alpha-1-microglobulin, glutathione transferase-pi (GST-pi), and
      glutathione transferase-alpha (GST-alpha) were measured after induction of
      anesthesia, at the end of surgery, and at the first and second postoperative days
      (PODs) on the intensive care unit. Patients' ages were 54 +/- 4 and 77 +/- 3 yr,
      respectively. Preoperative creatinine concentrations were without significant
      differences between the two groups. Fractional excretion of sodium was
      significantly higher after bypass in the elderly than in the younger patients.
      Urine concentrations of all kidney-specific proteins increased after CPB in the
      elderly (e.g., GST-pi from 16.2 +/- 3.4 to 27.7 +/- 3.9 microg/L), whereas they
      remained almost unchanged in the younger patients. Concentrations of all kidney
      specific proteins were significantly larger in the elderly than in the younger
      patients even at the second POD. Although none of our patients suffered ARF
      requiring dialysis, increased post-CPB urine concentrations of kidney-specific
      proteins in the elderly suggest discrete and transient alterations in kidney
      integrity in comparison with a younger patient population undergoing cardiac
      surgery. IMPLICATIONS: Measurement of kidney-specific proteins demonstrated that
      patients >70 yr (mean, 77 +/- 3 yr) undergoing cardiac surgery with
      cardiopulmonary bypass had moderate and transient alterations in kidney integrity
      compared with patients aged <60 yr (mean, 54 +/- 4 yr). These abnormalities were
      not detected with standard measures of kidney function (e.g., creatinine
      concentrations).

PMID- 14633525
TI  - Rapid water and slow sodium excretion of acetated Ringer's solution dehydrates
      cells.
AB  - Acetated Ringer's solution is a slightly hypotonic infusion fluid (osmolality 270
      mosmol/kg) that has inspired the belief that the fluid causes a shift of water
      volume to the intracellular space. We assessed the role of the kidney in
      modifying this volume shift by infusing 25 mL/kg of Ringer's acetate solution
      (mean, 1565 mL) over a time period of 15, 30, 45, and 80 min on different
      occasions in 5 healthy female volunteers. Regardless of the rate of
      administration, the excreted urine contained only half as much sodium (mean, 67
      mmol/L) as the infused fluid. As there was only a slight increase of 0.9 mmol/L
      in the serum sodium level, mass balance calculations indicated that 274 mL of
      water had shifted from the intracellular to the extracellular space 30 min after
      the infusions ended (P < 0.001). This fluid shift was also maintained over the
      subsequent 90 min. In conclusion, infusion of Ringer's acetate solution does not
      promote cellular swelling as a result of the excretion of urine that is low in
      sodium. A slight dehydration of fluid from the intracellular space still
      persisted when our measurements ended 2 h after completing the infusion.
      IMPLICATIONS: The kidney promotes slight cellular dehydration after infusion of
      Ringer's acetate solution by rapid excretion of water, whereas natriuresis occurs
      more slowly. In volunteers, this translocation amounted to 18% of the infused
      fluid volume and persisted for at least 2 h.

PMID- 14633526
TI  - New light on intravascular volume replacement regimens: what did we learn from
      the past three years?
AB  - Definition of the "ideal" intravascular fluid volume replacement strategy still
      remains a critical problem. This article analyzes studies on volume replacement
      by using a MEDLINE search of the past 3 years (from January 1, 2000, to December
      12, 2002). Forty original studies in humans with a total of 2454 subjects were
      identified. Five studies were performed in volunteers (n = 113); the other 35
      studies (n = 2341) were performed in a variety of patients (e.g., cardiac
      surgery, trauma patients, children, and intensive care unit patients). The
      influence of different volume replacement regimens on coagulation was one of the
      major topics of interest (16 studies with 1183 subjects), and other studies
      focused on metabolic state, alterations in macro- and microcirculation, volume
      distribution, and organ function (e.g., kidney function and splanchnic
      perfusion). Among all synthetic colloids, hydroxyethyl starch (HES) was the
      solution most often studied. Two new HES preparations have been approved
      (Hextend), a balanced hetastarch solution, and a new third-generation HES
      [130/0.4]). Only two studies used albumin, and no superiority of albumin was
      found over less expensive synthetic colloids. In almost all studies, the outcome
      either was no end-point or was not reported. Volume replacement has often been
      hitherto based on dogma and personal beliefs. Future well performed studies in
      this area will hopefully help to shed new light on the ideal volume replacement
      strategy. IMPLICATIONS: By using a MEDLINE search covering the last 3 yr, the
      present knowledge on volume replacement regimens was analyzed. Forty studies in
      humans were identified. New hydroxyethyl starch preparations have shed light on
      this topic, whereas no additional data supporting the use of albumin have been
      presented.

PMID- 14633527
TI  - Intramural left atrial hematoma after aortocoronary artery surgery.
AB  - We report the occurrence of an intraoperative left atrial hematoma during
      coronary artery bypass grafting surgery. Echocardiography proved to be of great
      help in diagnosis and monitoring of this patient. After severe hemodynamic
      impairment the patient recovered and could be transferred on postoperative day
      eight. Follow-up examination showed no signs of atrial pathologies. Differential
      diagnosis and echocardiographic findings are discussed. IMPLICATIONS: The authors
      report the utility of transesophageal echocardiography for diagnosis and
      management of an intramural left atrial hematoma during coronary artery surgery.

PMID- 14633528
TI  - Patient-controlled epidural analgesia versus continuous epidural infusion with
      ropivacaine for postoperative analgesia in children.
AB  - Epidural ropivacaine infusion has been used in children; however, patient
      controlled epidural analgesia (PCEA) has not been evaluated in the pediatric
      population. In this study, we compared the clinical efficiency of PCEA and of
      continuous epidural infusion analgesia (CEA) in children. Forty-eight children
      undergoing orthopedic surgery were randomized to receive PCEA or CEA with
      ropivacaine 0.2%. All patients underwent a standard general anesthetic. Children
      also received ketoprofen and propacetamol. Pain scores and side effects were
      recorded for 48 h. If the visual analog score scale score was >4 of 10, analgesia
      was considered inadequate, and rescue treatment was administered. Both groups
      obtained effective pain relief. Children in the PCEA group received significantly
      less local anesthetic than those in the CEA group (0.20 +/- 0.08 mg x kg(-1) x h(
      1) versus 0.40 +/- 0.08 mg x kg(-1) x h(-1); P < 0.001). Motor effects,
      supplemental analgesic requirements, and side effects did not differ. We
      concluded that PCEA with ropivacaine 0.2% can provide adequate postoperative
      analgesia for pediatric orthopedic procedures with smaller dose requirements than
      CEA. IMPLICATIONS: We studied patient-controlled epidural analgesia (PCEA) and
      continuous epidural infusion analgesia (CEA) with 0.2% ropivacaine during the
      postoperative period in children. We found that either PCEA or CEA with plain
      ropivacaine 0.2% provided adequate pain relief in children during the first 48-h
      postoperative course. However, adequate analgesia was obtained with 50% less
      volume infused with PCEA compared with CEA.

PMID- 14633529
TI  - Endotracheal tube cuff pressure is unpredictable in children.
AB  - The use of cuffed tracheal tubes in children younger than 8 yr of age has
      recently increased, although cuff hyperinflation may cause tracheal mucosal
      damage. In this study, we sought to measure the cuff pressure (P(cuff)) after
      initial free air inflation (iP(cuff)) and to follow its evolution throughout the
      duration of 50% nitrous oxide (N(2)O) anesthesia. One-hundred-seventy-four
      children, aged 0 to 9 yr, fulfilling the following criteria, were studied: 1).
      weight of 3-35 kg; 2). ASA physical status I or II; 3). elective surgery; 4).
      anesthesia with tracheal intubation using a cuffed tube and lasting at least 45
      min; and 5). gas mixture containing 50% N(2)O. Free air inflation results in
      variable iP(cuff), with hyperinflation in 39% of cases. Numerous gas removals
      were required to maintain P(cuff) less than 25 cm H(2)O in 85% of the patients.
      The number of deflations decreased with the duration of mechanical ventilation
      and was small after 105 min. No difference was observed among the different
      cuffed tube sizes. We conclude that iP(cuff) is unpredictable after free air
      inflation and that numerous gas removals are required to maintain P(cuff) less
      than 25 cm H(2)O during N(2)O anesthesia in children. IMPLICATIONS: Free
      inflation of the tracheal tube cuff, controlled only by the palpation of the
      pilot balloon, is not reliable and results in extremely variable (and sometimes
      very high) initial cuff pressures in children. In addition, nitrous oxide
      anesthesia may result in cuff hyperinflation requiring numerous gas removals.

PMID- 14633530
TI  - Transnasal placement of biplane transesophageal echocardiography probe
      intraoperatively in an adolescent with congenital heart disease.
AB  - Intraoperative transesophageal echocardiography (TEE) is frequently used in
      children with congenital heart disease (CHD). Although transnasal TEE is being
      used in various settings in the adult population, there are no descriptions of
      its use intraoperatively in patients with CHD. This report describes the
      successful use of transnasal TEE after multiple unsuccessful transoral attempts
      in an adolescent male undergoing subaortic stenosis repair. IMPLICATIONS:
      Transnasal transesophageal echocardiography (TEE) is being used in various
      settings in the adult population. The author describes its use intraoperatively
      in an adolescent undergoing surgery for congenital heart disease after
      unsuccessful transoral attempts.

PMID- 14633531
TI  - Preoperative interscalene block for elective shoulder surgery: loss of benefit
      over early postoperative block after patient discharge to home.
AB  - We performed a randomized, prospective, parallel-group, open-label, multicenter
      trial to compare the effects of pre- versus postoperative interscalene block
      using levobupivacaine on postoperative pain and analgesic requirements. One
      hundred-two outpatients scheduled for elective shoulder surgery were randomized
      to receive 30 mL of 0.5% levobupivacaine either preoperatively (PRE group) or
      postoperatively (POST group). Analgesic outcome measures during the postoperative
      period were: (a). time to first request for analgesic medication after surgery,
      (b). pain intensity using the visual analog scale at rest and during arm
      movement, and (c). total analgesic consumption of nonsteroidal antiinflammatory
      drugs and opioids. The time to first analgesic request did not differ between
      treatment groups. However, mean maximum pain intensity scores during the day of
      surgery were significantly less for the PRE group than the POST group, both at
      rest (P = 0.001) and after movement (P = 0.004). The mean opioid administered
      during surgery was lower in the PRE than the POST group (P < 0.001).
      Levobupivacaine was well tolerated in both treatment groups, and no adverse
      reactions were related to this local anesthetic. In conclusion, preoperative
      interscalene block with levobupivacaine provided superior pain control for the
      first 12 h after surgery, but this benefit was not maintained during the week
      after discharge because the subjects assumed control of their own pain relief as
      outpatients. IMPLICATIONS: Preoperative interscalene block with levobupivacaine
      provides safe and effective analgesia for same-day elective shoulder surgery, but
      the benefit of this one-time intervention does not persist.

PMID- 14633532
TI  - Preincisional treatment to prevent pain after ambulatory hernia surgery.
AB  - We designed this study as a randomized comparison of postoperative pain after
      inguinal hernia repair in patients treated with triple preincisional analgesic
      therapy versus standard care. Triple therapy consisted of a nonsteroidal
      antiinflammatory, a local anesthetic field block, and an N-methyl-D-aspartate
      inhibitor before incision. The treatment group (n = 17) received rofecoxib, 50 mg
      PO, a field block with 0.25% bupivacaine/0.5% lidocaine, and ketamine 0.2 mg/kg
      IV before incision; controls (n = 17) received a placebo PO before surgery. The
      anesthetic protocol was standardized. Postoperative pain was treated by fentanyl
      IV and oxycodone 5 mg/acetaminophen 325 mg PO as required for pain. Pain scores
      (0-10) and analgesic were recorded for the first 7 days after surgery. Pain
      scores were 47% lower in the treatment group before discharge (3.1 +/- 0.6 versus
      5.9 +/- 0.6, P = 0.0026) (mean +/- SE) and 18% less in the first 24 h after
      discharge (5.6 +/- 0.4 versus 6.8 +/- 0.5, P = 0.05); oral analgesic use was 34%
      less in the treatment group (4.6 +/- 0.8 doses versus 7.1 +/- 0.7 doses, P =
      0.02) in the first 24 h after surgery. We conclude that triple preincisional
      therapy diminishes pain and analgesic use after outpatient hernia repair, and
      encourage further evaluation of this technique. IMPLICATIONS: Outpatients
      undergoing inguinal hernia repair under general anesthesia report moderate-to
      severe pain after surgery. Triple preincisional therapy that included rofecoxib,
      50 mg PO, ketamine, 0.2 mg/kg IV, and local anesthetic field block reduced pain
      scores and analgesic use in the first 24 h after discharge.

PMID- 14633533
TI  - The effect of intraoperative use of esmolol and nicardipine on recovery after
      ambulatory surgery.
AB  - There is controversy regarding the optimal technique for maintaining hemodynamic
      stability during anesthesia. We designed this prospective, randomized, double
      blinded study to test the hypothesis that the technique used for maintaining
      hemodynamic stability during general anesthesia can influence recovery after
      ambulatory surgery. Forty-five healthy consenting women undergoing gynecologic
      laparoscopy procedures were randomly assigned to 1 of 3 treatment groups: Group 1
      (control, n = 15) received normal saline 5 mL and 1 mL, followed by a saline
      infusion at a rate of 0.005 mL x kg(-1) x min(-1); Group 2 (n = 15) received
      esmolol 50 mg and saline 1 mL, followed by an esmolol infusion 5 microg x kg(-1)
      x min(-1); and Group 3 (n = 15) received esmolol 50 mg and nicardipine 1 mg,
      followed by an esmolol infusion 5 microg x kg(-1) x min(-1). The study drugs were
      administered after the induction of anesthesia with fentanyl 1.5 microg/kg, and
      propofol 2 mg/kg I.V. Tracheal intubation was facilitated with vecuronium 0.12
      mg/kg I.V. Anesthesia was initially maintained with desflurane 2% end-tidal and
      N(2)O 67% in oxygen in all 3 groups. During surgery, the mean arterial blood
      pressure (MAP) was maintained within +/-15% of the baseline value by varying the
      study drug infusion rate and the inspired concentration of desflurane. In
      addition to MAP and heart rate values, electroencephalogram bispectral index
      values were recorded throughout the perioperative period. Recovery times and
      postoperative side effects were assessed. Compared with the control group,
      adjunctive use of esmolol and nicardipine attenuated the increase in heart rate
      (in Group 2) and MAP (in Group 3) after tracheal intubation. Furthermore, the use
      of an esmolol infusion as an adjunct to desflurane to control the acute autonomic
      responses during the maintenance period significantly decreased emergence times
      (4 +/- 2 versus 7 +/- 4 min), decreased the need for postoperative opioid
      analgesics (43% versus 80%), and reduced the time to discharge (209 +/- 89 versus
      269 +/- 100 min). We conclude that the adjunctive use of esmolol alone or in
      combination with nicardipine during the induction of anesthesia reduced the
      hemodynamic response to tracheal intubation. Furthermore, use of an esmolol
      infusion as an adjuvant to desflurane-N(2)O anesthesia for controlling the acute
      hemodynamic responses during the maintenance period improved the recovery profile
      after outpatient laparoscopic surgery. IMPLICATIONS: The adjunctive use of the
      beta-adrenergic blocker esmolol to control the acute sympathetic responses during
      desflurane-based anesthesia provided a more rapid awakening from anesthesia,
      reduced the postoperative opioid analgesic requirement, and decreased the time to
      discharge home after ambulatory laparoscopic surgery.

PMID- 14633534
TI  - The mechanisms of propofol-mediated hyperpolarization of in situ rat mesenteric
      vascular smooth muscle.
AB  - Previously, we reported that propofol hyperpolarizes vascular smooth muscle (VSM)
      cells of small arteries and veins. The current study was designed to determine
      whether propofol-mediated hyperpolarization is the result of specific effects on
      potassium channels known to exist in VSM and on steps in the intracellular nitric
      oxide (NO), cyclic guanosine monophosphate (cGMP), and cyclic adenosine
      monophosphate (cAMP) second messenger pathways. VSM transmembrane potentials
      (E(m)) were measured in situ in sympathetically denervated, small mesenteric
      arteries and veins of Sprague-Dawley rats. Effects of propofol on VSM E(m) were
      determined before and during superfusion with specific inhibitors of VSM calcium
      activated (K(Ca)), adenosine triphosphate-sensitive (K(ATP)), voltage-dependent
      (K(v)), and inward rectifying (K(IR)) potassium channels and with endogenous
      mediators of vasodilation. Propofol significantly hyperpolarized VSM in small
      mesenteric vessels. This hyperpolarization was abolished on inhibition of K(Ca)
      and K(ATP) channel activity and on inhibition of NO and cGMP (but not cAMP).
      Assuming a close inverse correlation between the magnitude of VSM E(m) and
      contractile force, these results suggest that propofol induces hyperpolarization
      and relaxation in denervated, small mesenteric vessels by activation of K(Ca) and
      K(ATP) channels. Such channel activation may be mediated by activation of NO and
      cGMP, but not cAMP, second messenger pathways. IMPLICATIONS: The results of this
      study indicate that propofol-mediated hyperpolarization in vascular smooth muscle
      can be attributed to the activation of calcium-activated, adenosine triphosphate
      sensitive potassium channels, the nitric oxide, and cyclic guanosine
      monophosphate pathways.

PMID- 14633535
TI  - Physicochemical compatibility of propofol-lidocaine mixture.
AB  - To examine the physicochemical stability of combinations of propofol-lidocaine
      mixtures frequently used in clinical practice, we added lidocaine 5, 10, 20, or
      40 mg to commercially available 1% propofol 20 mL. To assess chemical stability,
      propofol concentrations were determined by gas chromatography assay for 24 h
      after preparation of the mixture. In addition, scanning electron microscopy was
      used to determine the maximum detectable droplet size in randomly selected
      fields. Macroscopically, separate, colorless layers were first seen at 3 and 24 h
      after the addition of 40 and 20 mg of lidocaine to propofol, respectively,
      whereas the mixture with 5 or 10 mg of lidocaine was macroscopically stable.
      Propofol concentrations in the mixture with 40 mg of lidocaine decreased linearly
      and significantly from 4 to 24 h after preparation, whereas those combined with
      other lidocaine doses were unchanged compared with baseline concentrations.
      Scanning electron microscopy showed that droplets with diameters >or=5 microm
      first appeared 30 min after the addition of 40 mg of lidocaine to propofol, and
      the emulsion droplets were enlarged in a time- and dose-dependent fashion. Our
      results indicate that the addition of lidocaine to propofol results in a
      coalescence of oil droplets, which finally proceeds to a visible separate layer.
      Depending on the dose of lidocaine and the duration between its preparation and
      administration, this combination may pose the risk of pulmonary embolism.
      IMPLICATIONS: The addition of lidocaine to propofol results in time- and dose
      dependent increases in oil droplet diameters in emulsion. This mixture is
      physicochemically unstable over time and may cause pulmonary embolism, depending
      on the dose of lidocaine.

PMID- 14633536
TI  - The effect of antiemetics on pupillary reflex dilation during epidural/general
      anesthesia.
AB  - The effect of dopamine D2 receptor antagonists, such as chlorpromazine and
      haloperidol, on pupil size in awake subjects suggests that these drugs might also
      alter pupillary reflex dilation and pupil size during general anesthesia. Forty
      seven patients undergoing lower abdominal surgery under combined epidural/general
      anesthesia were randomized to receive one of the 5 following open labeled drugs:
      10 mL saline, 0.13 mg/kg ondansetron, 0.25 mg/kg metoclopramide, 0.5 mg/kg
      metoclopramide, or 0.02 mg/kg droperidol. Three measurements of reflex dilation
      were taken at 5-min intervals and after the last measurement (time 0) the drug
      was administered. Measurements were then taken 5, 10, 20, and 40 min after I.V.
      drug administration. Reflex dilation was induced by intermittent noxious
      stimulation of the C5 dermatome with a tetanic electric current (60-70 mamp, 100
      Hz, 3-s duration) after a stable level of epidural analgesia had been established
      with 3/8% bupivacaine and maintained with a continuous infusion. Metoclopramide
      produced a small decrease in pupil diameter and transiently depressed reflex
      dilation, whereas droperidol decreased pupil size at 10 min and depressed reflex
      dilation throughout the 40-min study period. Maximal change in reflex dilation
      was -6.6 +/- 3.3 mm-sec after droperidol. Ondansetron had no effect on pupil
      diameter or reflex dilation. When pupillary diameter measurements are used to
      gauge opioid levels during experimental conditions or during surgical anesthesia,
      antiemetic medication acting on the dopamine D2 receptor should be avoided.
      IMPLICATIONS: Miosis is often considered an effect of opioid administration
      during general anesthesia, but other drugs, such as antiemetics, might produce a
      similar effect on the pupil. This study demonstrates that 2 antiemetics,
      droperidol and metoclopramide, constrict the pupil and block the pupillary
      dilation brought about by nociceptive stimuli.

PMID- 14633537
TI  - The use of bone cement induces an increase in serum astroglial S-100B protein in
      patients undergoing total knee arthroplasty.
AB  - Cerebral microemboli can occur during arthroplasty with the use of bone cement.
      Astroglial S-100B protein is a sensitive marker of cerebral damage. Therefore, we
      designed this study to determine the effect of bone cement on the brain by
      investigating serum levels of S-100B protein in patients undergoing bone surgery
      with or without bone cement. Fourteen patients undergoing knee arthroplasty (n =
      7) or reamed intramedullary nailing for tibial fracture (n = 7) requiring a
      pneumatic tourniquet were enrolled in this study. Bone cement containing
      polymethyl methacrylate and methyl methacrylate was used for every patient
      undergoing knee arthroplasty. Serum samples were obtained from venous blood
      before the induction of general anesthesia, 15 min after deflation of a pneumatic
      tourniquet, and 3 days after the operation. The serum level of S-100B protein was
      significantly increased 15 min after a pneumatic tourniquet deflation in the knee
      arthroplasty group compared with the tibial fracture group (0.41 and 0.08 ng/mL,
      respectively; P < 0.05). In all patients studied, no neurological abnormalities
      were noted in the postoperative period. These results suggest that, in patients
      undergoing knee arthroplasty, bone cement may transiently induce astroglial
      injury, although it does not alter neurological outcome. IMPLICATIONS: Serum S
      100B protein was significantly increased 15 min after a pneumatic tourniquet
      deflation in patients undergoing knee arthroplasty with bone cement, but not in
      those undergoing reamed intramedullary nailing for tibial fracture without bone
      cement. These results suggest that bone cement may transiently induce astroglial
      injury.

PMID- 14633538
TI  - Preoperative fentanyl infusion with pharmacokinetic simulation for anesthetic and
      perioperative management of an opioid-tolerant patient.
AB  - For opioid-tolerant patients, conventional patient-controlled analgesia dosing
      may be ineffective. We present a cardiac surgery patient with a history of
      significant opioid tolerance and prior episodes of severe postoperative pain.
      Using the patient's response to a large-dose fentanyl infusion in conjunction
      with a pharmacokinetic simulation, effective intraoperative and postoperative
      fentanyl plasma concentrations were achieved. IMPLICATIONS: A preinduction
      fentanyl infusion used in conjunction with pharmacokinetic simulation can be a
      useful tool for assessing individual limits of opioid tolerance, as well as
      determining an appropriate dose for acute pain management in opioid-tolerant
      patients.

PMID- 14633539
TI  - Orexin a elicits arousal electroencephalography without sympathetic
      cardiovascular activation in isoflurane-anesthetized rats.
AB  - We studied the effects of intracerebroventricular injection of the novel
      neuropeptide orexin A on electroencephalogram (EEG) and autonomic nervous system
      activity in rats under isoflurane anesthesia. The administration of orexin A
      changed burst suppression patterns to arousal patterns on the EEG at 1.0 minimum
      alveolar anesthetic concentration (MAC) isoflurane and decreased the burst
      suppression ratio at 1.5 MAC isoflurane. However, orexin A did not influence the
      heart rate or mean arterial blood pressure at either isoflurane concentration.
      These findings demonstrated that orexin A elicited anesthetic arousal under
      isoflurane anesthesia in terms of EEG pattern without sympathetic cardiovascular
      activation in the rat. IMPLICATIONS: The novel neuropeptides orexins induce
      arousal associated with activation of the sympathetic nervous system in conscious
      rats. It is not known whether orexins affect the electroencephalogram (EEG),
      autonomic nerve activity, or both under anesthesia. Orexin A induced EEG arousal
      without sympathetic cardiovascular activation in the isoflurane-anesthetized rat.
      Orexin A might influence the depth of anesthesia.

PMID- 14633540
TI  - The effect of cerebral monitoring on recovery after general anesthesia: a
      comparison of the auditory evoked potential and bispectral index devices with
      standard clinical practice.
AB  - The use of cerebral monitoring may improve the ability of anesthesiologists to
      titrate anesthetic drugs. However, there is controversy regarding the impact of
      the alleged anesthetic-sparing effects of cerebral monitoring on the recovery
      process and patient outcome. We designed this prospective double-blinded, sham
      controlled study to evaluate the impact of intraoperative monitoring with the
      electroencephalogram bispectral index (BIS) or auditory evoked potential (AEP)
      device on the usage of desflurane and the time to discharge from the recovery
      room, as well as on patient satisfaction with their anesthetic experience and
      recovery. Ninety healthy patients undergoing laparoscopic general surgery
      procedures using a standardized anesthetic technique were randomly assigned to
      one of three monitoring groups: standard clinical practice (control), BIS-guided,
      or AEP-guided. Both the BIS and AEP monitors were connected to all patients
      before induction of general anesthesia. In the control group, the
      anesthesiologists were not permitted to observe the BIS or AEP index values
      during the intraoperative period. In the BIS-guided group, the volatile
      anesthetic was titrated to maintain a BIS value in the range of 45-55. In the AEP
      guided group, the targeted AEP index range was 15-20. The BIS and AEP indices, as
      well as end-tidal desflurane concentration, were recorded at 3-5 min intervals.
      Recovery times to awakening, tracheal extubation, fast-track score >or=12, and
      postanesthesia care unit (PACU) discharge criteria were recorded at 1-10 min
      intervals. In addition, patient satisfaction with anesthesia and quality of
      recovery were evaluated on 100- and 18-point scales, respectively, at 24 h after
      surgery. The AEP- and BIS-guided groups were administered significantly smaller
      average end-tidal desflurane concentrations than the control group (3.8 +/- 0.9
      and 3.9 +/- 0.6 versus 4.7 +/- 1.7, respectively) (P < 0.01). Although the
      emergence times to eye opening, tracheal extubation, and obeying commands were
      consistently shorter in the AEP and BIS groups (6 +/- 4 and 6 +/- 5 versus 8 +/-
      8 min; 6 +/- 5 and 6 +/- 4 versus 11 +/- 10 min; and 8 +/- 4 and 7 +/- 4 versus
      12 +/- 9 min, respectively), only the extubation times were significantly
      different from the control group (P < 0.05). More importantly, the length of the
      PACU stay was significantly shorter in both the AEP- and BIS-guided groups (79 +/
      43 and 80 +/- 47 versus 108 +/- 58 min, respectively) (P < 0.05). The patients'
      quality of recovery was also significantly higher in the two monitored groups (15
      +/- 2 versus 13 +/- 3 in the control group, P < 0.05). We concluded that cerebral
      monitoring with either the BIS or AEP devices reduced the maintenance anesthetic
      (desflurane) requirement, resulting in a shorter length of stay in the PACU and
      improved quality of recovery after laparoscopic surgery. However, there were no
      significant outcome differences between the two cerebral monitored groups.
      IMPLICATIONS: Compared with standard monitoring practices, use of an auditory
      evoked potential or bispectral index monitor to titrate the volatile anesthetic
      led to a significant reduction in the anesthetic requirement. The anesthetic
      sparing effect of cerebral monitoring resulted in a shorter postanesthesia care
      unit stay and improved quality of recovery from the patient's perspective.

PMID- 14633541
TI  - Transcranial Doppler monitoring during laparoscopic anterior lumbar interbody
      fusion.
AB  - We studied the consequences on cerebral hemodynamics of lengthy laparoscopic
      procedures requiring pneumoperitoneum and head-down positioning. From October
      1995 to April 1999, 17 ASA status I or II patients (16 women and 1 man; mean age,
      38 yr) were treated with laparoscopic anterior lumbar fusion. Besides standard
      perioperative monitoring for laparoscopic surgery, the mean blood-flow velocity
      of both middle cerebral arteries and the pulsatility index were determined by
      transcranial Doppler ultrasound. Adequate acoustic windows were encountered in 11
      of the 17 patients, and the remaining 6 were excluded from the analysis. PaCO(2)
      and end-tidal CO(2) were maintained within normal limits (<40 mm Hg); ventilation
      was optimized in all cases. There was a significant increase (P < 0.05) in heart
      rate and central venous pressure with the change from supine to head-down
      position in all patients. Transcranial Doppler results for mean middle cerebral
      artery blood-flow velocity and pulsatility index showed no significant variations
      at any of the four time points studied during the procedure. There were no
      technique-related complications, except for moderate postoperative headache in
      eight patients that resolved with rest and oxygen therapy. We conclude that
      lengthy laparoscopic procedures in the head-down position performed in otherwise
      healthy patients do not significantly affect intracranial circulation.
      IMPLICATIONS: This study assessed the consequences of lengthy laparoscopic
      surgery with head-down (Trendelenburg) positioning on cerebral blood circulation
      by transcranial Doppler ultrasound, a noninvasive technique. It is important to
      investigate whether there are cerebral hemodynamic changes because these may be
      detrimental to some patients for whom this surgery is considered.

PMID- 14633542
TI  - Oxygen consumption measurement: agreement between the closed-circuit PhysioFlex
      anesthesia machine and the Deltatrac II indirect calorimeter.
AB  - We designed this study to ascertain whether, for the purpose of clinical
      interpretation, the direct measurement of O(2) consumption with the PhysioFlex
      closed-circuit anesthesia machine and with the Deltatrac II indirect calorimeter
      are interchangeable. Oxygen consumption was measured using the two instruments
      successively in critically-ill, mechanically-ventilated patients. Measurements
      were recorded as the mean of 10 consecutive, minute-by-minute, stable readings.
      The degree of agreement between the measurements obtained with the two systems
      was estimated using Bland-Altman analysis and the intraclass correlation
      coefficient. Forty-four pairs of measurements made in 21 patients were analyzed,
      yielding a mean bias of 6.32 mL/min and limits of agreement of 40.28 and -27.63
      mL/min. The intraclass correlation coefficient was 0.95, and the 95% confidence
      interval ranged from 0.91 to 0.97. The measurement of O(2) consumption obtained
      with the PhysioFlex anesthesia machine is interchangeable with that obtained by
      indirect calorimetry. IMPLICATIONS: The PhysioFlex anesthesia machine (Drager
      Inc., Lubeck, Germany) is a closed circuit anesthesia delivery device. The oxygen
      delivered by this device to maintain a steady-state inspired oxygen concentration
      is therefore a measure of the patient's oxygen consumption. This study was
      designed to evaluate the accuracy of the PhysioFlex for measuring oxygen
      consumption by comparing it with an established technology (Deltatrac II
      Calorimeter) for making this measurement.

PMID- 14633543
TI  - A pilot study to evaluate the SMART BAG: a new pressure-responsive, gas-flow
      limiting bag-valve-mask device.
AB  - Reducing inspiratory flow rate and peak airway pressure may be important to
      minimize the risk of stomach inflation when ventilating an unprotected airway
      with positive pressure ventilation. In this study, we assessed the effects of a
      standard self-inflating bag compared with a new pressure-responsive, inspiratory
      gas flow-limiting device (SMART BAG) on respiratory mechanics in 60 adult
      patients undergoing routine induction of anesthesia. Respiratory variables were
      measured using a pulmonary monitor. The SMART BAG resulted in significantly
      decreased inspiratory flow rate and peak airway pressure while providing adequate
      tidal volume delivery. IMPLICATIONS: The SMART BAG, a new pressure-responsive,
      peak inspiratory gas flow-limiting bag-valve mask device, limits inspiratory gas
      flow from up to 120 L/min in a standard self-inflating bag to approximately 40
      L/min. It is designed for use by all levels of health care professionals and has
      been proven in a clinical pilot study to effectively ventilate patients in
      respiratory arrest.

PMID- 14633544
TI  - Identification of gaps in the achievement of undergraduate anesthesia educational
      objectives using high-fidelity patient simulation.
AB  - In this study we sought to identify educational gaps in medical students'
      knowledge using human patient simulation. The Undergraduate Committee developed
      10 scenarios based on anesthesia curriculum objectives. Checklists were designed
      by asking 15 faculty members involved in undergraduate education to propose
      expected performance items at a level appropriate for medical students. These
      items consisted of essential performance items as well as critical management
      omissions. Checklists were used to score students' videotaped performances.
      Checklist items common to more than one scenario were grouped for data analysis
      and identification of gaps in achievement of educational objectives. Eighteen
      groupings of expected performance criteria and 8 groupings of critical management
      omissions were established. Performance data of 165 students were analyzed.
      Common management omissions were lack of adequate airway management, failure to
      check blood pressure, and failure to stop the anesthetic. Students reliably
      performed defibrillation, notation of vital signs, auscultation of lung fields,
      and administration of IV fluids. The most common critical omissions were failing
      to a). call for help, b). take a history/do physical examination, and c). prepare
      airway equipment. Management and critical omissions noted during performance
      assessments provide information regarding students' educational needs, enabling
      faculty to focus attention on demonstrated areas of weakness. IMPLICATIONS: This
      study involved the use of high-fidelity patient simulation that offers
      standardized clinical experiences that can detect gaps in medical students'
      knowledge base and clinical performance. This information can be used by faculty
      to focus their teaching efforts to ensure competency in important educational
      areas.

PMID- 14633545
TI  - General concepts in full scale simulation: getting started.
AB  - Over the past decade, medical simulation has developed to a point where it now is
      poised to become ubiquitous in teaching curricula. Despite this experience, there
      is little up-to-date information to help new instructors and operators learn the
      general principles of simulation. The purpose of this article is to provide
      prospective simulation instructors with basic concepts and a practical approach
      to patient simulation. The main focus is on full-scale or high fidelity
      simulation. The article is intended to (a). prepare instructors to use full-scale
      simulation to educate students; (b). teach some of the complexities and
      terminology of simulation; (c). prepare for and complement the curriculum of a
      formal instructor course; and (d). teach the basic elements required to run a
      successful simulation. This article should be used as an adjunct to practical
      experience gained from using simulation units. IMPLICATIONS: Medical simulation
      replicates normal and abnormal physiology and pathology. It is a tool that is
      intended to increase experiential learning. Establishing a functional and useful
      simulation program involves many factors. This paper presents a detailed
      introduction to the concepts and methodology of simulation in medicine.

PMID- 14633546
TI  - Contact dermatitis after the use of the PronePositioner.
AB  - The PronePositioner is used to support the head during prone position procedures.
      We present the first case report of allergic contact dermatitis from the
      PronePositioner. The patient was sensitized to the urethane in the
      PronePositioner during his many previous surgeries. We caution its repeated use
      in a single patient secondary to concerns of sensitization. IMPLICATIONS: We
      present the first case report of allergic contact dermatitis from the
      PronePositioner. We caution its repeated use in a single patient secondary to
      concerns of sensitization to the urethane in the PronePositioner.

PMID- 14633547
TI  - Optimizing the dose of intrathecal morphine in older patients undergoing hip
      arthroplasty.
AB  - Intrathecal (IT) morphine provides excellent postoperative analgesia but may
      result in many side effects, including postoperative nausea and vomiting,
      pruritus, and respiratory depression, particularly at larger doses. Older
      patients may be at particular risk. The optimal dose of spinal morphine in older
      patients undergoing hip arthroplasty is not known. We designed this prospective,
      randomized, controlled, double-blinded study to evaluate the analgesic efficacy
      and side effect profile of 50-200 microg of IT morphine in older patients
      undergoing elective hip arthroplasty. Sixty patients older than 65 years
      undergoing elective hip arthroplasty were enrolled. Patients were randomized to
      receive spinal anesthesia with 15 mg of bupivacaine and IT morphine in four
      groups: 1). 0 microg, 2). 50 microg, 3). 100 microg, and 4). 200 microg. IT
      morphine 100 and 200 microg produced effective pain relief and decreased the
      postoperative requirement for morphine compared with control. IT morphine 50
      microg did not provide effective pain relief. Both 100 and 200 microg of IT
      morphine provided comparable levels of postoperative analgesia. There were no
      between-group differences in postoperative nausea and vomiting, sedation,
      respiratory depression, or urinary retention. Pruritus was significantly more
      frequent with 200 microg of IT morphine. In conclusion, 100 microg of IT morphine
      provided the best balance between analgesic efficacy and side effect profile in
      older patients undergoing hip arthroplasty. IMPLICATIONS: The dosage of
      intrathecal morphine that provides the best balance between analgesic efficacy
      and side effect profile in the older patient undergoing hip arthroplasty is not
      known. This prospective, randomized, controlled, double-blinded clinical trial
      demonstrates that a dose of 100 microg of intrathecal morphine provides the best
      balance between efficacy and side effects, compared with doses of 0, 50, and 200
      microg of morphine, in this patient population.

PMID- 14633548
TI  - The neurotoxicity of epidural hyaluronic acid in rabbits: a light and electron
      microscopic examination.
AB  - Because hyaluronic acid (HA) has an antiinflammatory effect and prevents and/or
      reduces tissue adhesion, we believed it possible that epidurally-administered HA
      during epidural adhesiolysis procedures could alleviate pain in patients with
      chronic lower back pain. Therefore, we performed this pre-clinical trial
      evaluation of epidurally-administered HA neurotoxicity by light microscopy (LM)
      and electron microscopy (EM) in rabbits. Twenty rabbits were randomly divided
      into two groups, a normal saline (NS) group (n = 10) and a HA group (n = 10).
      Saline (0.2 mL/kg of 0.9% solution) and the same volume of HA were injected into
      the epidural space. No rabbits showed any sensory-motor or behavior change during
      the 3-wk period, except for one rabbit in the NS group that showed decreased
      appetite, activity, and weight loss. By LM, two rabbits in the NS group showed
      abnormal findings considered to be the result of trauma and infection associated
      with epidural catheterization. EM findings showed no significant neurotoxic
      findings in either group. In conclusion, epidurally-administered HA did not cause
      neurotoxicity in rabbits. IMPLICATIONS: We performed a pre-clinical trial
      evaluation on the neurotoxicity of hyaluronic acid administered epidurally by
      light microscopy and electron microscopy in rabbits. Epidurally-administered
      hyaluronic acid did not produce any sign of neurotoxicity in rabbits.

PMID- 14633549
TI  - The synergistic analgesic interactions between hydrocodone and ibuprofen.
AB  - The practice of combining opioids with nonsteroidal antiinflammatory drugs is
      widespread in the clinical management of acute and chronic pain. Using the mouse
      radiant heat tail-flick nociception model, we observed potent analgesia with
      hydrocodone. In contrast, ibuprofen as a single drug was inactive in this model
      of moderate to severe pain, perhaps reflecting its limited analgesic potential.
      Despite the inactivity of ibuprofen alone in this model, the inclusion of
      ibuprofen with hydrocodone markedly enhanced the analgesic response. Dose
      response studies revealed an 50% effective dose for hydrocodone alone in mice of
      11 mg/kg, SC. Inclusion of a fixed ibuprofen dose with the various hydrocodone
      doses shifted the 50% effective dose value almost seven-fold to the left to 1.6
      mg/kg, SC, despite the lack of effect of ibuprofen alone in this model. Using a
      fixed hydrocodone:ibuprofen ratio (1:40) also revealed a marked four-fold shift
      to 2.6 mg/kg, SC. These findings suggest a synergistic interaction between
      ibuprofen and hydrocodone in a noninflammatory pain model. IMPLICATIONS: Opioids
      are frequently used in combination with nonsteroidal antiinflammatory drugs
      clinically. These studies demonstrate strong interactions between ibuprofen and
      hydrocodone, implying synergy between the two drugs, which may help explain their
      utility when given together.

PMID- 14633550
TI  - The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked
      thermal hyperalgesia.
AB  - We tested baicalin for its antiinflammatory and analgesic effects (and the
      mechanisms) in a rat model of carrageenan-evoked thermal hyperalgesia. Pre- or
      posttreatment with baicalin (10, 30, or 100 mg/kg intraperitoneally) caused a
      significant analgesic effect with a similar effect of dose-matched ibuprofen.
      Furthermore, baicalin dose-dependently attenuated tumor necrosis factor-alpha
      (from 3510 +/- 150 pg/mL to 2860 +/- 148 pg/mL to 1480 +/- 210 pg/mL),
      interleukin (IL)-1beta (from 3210 +/- 210 pg/mL to 2200 +/- 140 pg/mL to 750 +/-
      95 pg/mL), and IL-6 (from 58.5 +/- 9.8 pg/mL to 38.5 +/- 9.0 to 21.0 +/- 8.1
      ng/mL) formation but enhanced IL-10 (from 18.1 +/- 2.5 pg/mL to 36.1 +/- 5.5
      pg/mL to 71.2 +/- 9.5 pg/mL) production in paw exudates at 4 h after carrageenan
      injection. Prostaglandin E(2) (PGE(2)) and nitrate formation in the carrageenan
      injected paws were dose-dependently inhibited by baicalin (10-100 mg/kg
      intraperitoneally) (PGE(2): from 15.9 +/- 2.1 ng/mL to 12.1 +/- 1.6 ng/mL to 6.2
      +/- 1.8 ng/mL; nitrate: from 39.8 +/- 4.8 microM to 27.5 +/- 3.0 microM to 17.2
      +/- 1.6 microM) at 4 h but not at 1.5 h after carrageenan injection. Increased
      myeloperoxidase activity in carrageenan-injected paws was also dose-dependently
      reduced by baicalin. These findings suggest that the antiinflammatory and
      analgesic mechanisms of baicalin may be associated with the inhibition of
      critical inflammatory mediators, including nitric oxide, PGE(2), and
      proinflammatory cytokines, accompanied by an increase in IL-10 production, as
      well as neutrophil infiltration at sites of inflammation. IMPLICATIONS: Our
      results showed that baicalin possesses an analgesic effect in carrageenan-evoked
      thermal hyperalgesia. The possible mechanisms of action of baicalin may be
      associated with the inhibition of proinflammatory mediator overproduction,
      including cytokines, nitric oxide, and prostaglandin E(2), as well as neutrophil
      infiltration. This implies that baicalin may be a potential therapeutic analgesic
      for inflammatory pain.

PMID- 14633551
TI  - Ketamine in chronic pain management: an evidence-based review.
AB  - Ketamine has diverse effects that may be of relevance to chronic pain including:
      N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated
      Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in
      clinical practice for over 30 yr; however, there has been little formal research
      on the effectiveness of ketamine for chronic pain management. In this review we
      evaluate the available clinical data as a basis for defining the potential use of
      ketamine for chronic pain. Literature referenced in this review was obtained from
      a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search
      terms included ketamine, ketalar, pain, painful, analgesic, and analgesia.
      Abstracts were screened for relevance and publications relating to chronic pain
      use were obtained. Levels of evidence were stratified according to accepted
      guidelines (level I-IV). For central pain, there is level II and level IV
      evidence of efficacy for parenteral and oral ketamine. For complex regional pain
      syndromes, there is only level IV evidence of efficacy of epidural ketamine. For
      fibromyalgia, there is level II evidence of pain relief, reduced tenderness at
      trigger points, and increased endurance. For ischemic pain, a level II study
      reported a potent dose-dependent analgesic effect, but with a narrow therapeutic
      window. For nonspecific neuropathic pain, level II and level IV studies reported
      divergent results with questionable long-term effects on pain. For phantom limb
      pain and postherpetic neuralgia, level II and level II studies provided objective
      evidence of reduced hyperpathia and pain relief was usually substantial either
      after parenteral or oral ketamine. Acute on chronic episodes of severe
      neuropathic pain represented the most frequent use of ketamine as a "third line
      analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the
      evidence for efficacy of ketamine for treatment of chronic pain is moderate to
      weak. However, in situations where standard analgesic options have failed
      ketamine is a reasonable "third line" option. Further controlled studies are
      needed.

PMID- 14633552
TI  - Epidural analgesia at end of life: facing empirical contraindications.
AB  - In a patient with unbearable cancer pain at the end of life, long-lasting
      analgesia without impairment of consciousness could only be achieved with an
      epidural infusion of local anesthetics combined with opioids and clonidine.
      Despite leptomeningeal infection during prolonged treatment, epidural analgesia
      at the lumbar level provided analgesia using very large doses of local
      anesthetics combined with clonidine and morphine. Thus, terminal sedation was
      avoided, allowing the patient's end-of-life planning of an "aware" death
      surrounded by her family. It may be useful to reconsider institutional pain
      management standards when unbearable pain occurs in patients with limited life
      expectancy. IMPLICATIONS: We report a patient with severe visceral and neurogenic
      pain from metastatic carcinoma of the colon resistant to multimodal oral
      analgesic therapy. Although there were empirical contraindications, epidural
      analgesia was successful, allowing the patient's end-of-life planning of an
      "aware" death surrounded by the family.

PMID- 14633553
TI  - Automatic "respirator/weaning" with adaptive support ventilation: the effect on
      duration of endotracheal intubation and patient management.
AB  - Adaptive support ventilation (ASV) provides an automatic adaptation of the
      ventilator settings to patient's passive and active respiratory mechanics. In a
      randomized controlled study, we evaluated automatic respiratory weaning in ASV
      for early tracheal extubation after cardiac surgery. Eligible patients were
      assigned to either an ASV protocol or a standard one consisting of synchronized
      intermittent ventilation followed by pressure support. Eighteen patients
      completed the ASV protocol, and 16 completed the standard one. There were no
      differences between groups in perioperative characteristics, lengths of tracheal
      intubation and intensive care unit stay, and ventilatory variables, except less
      peak inspiratory pressure during the initial phase in ASV (17.5 +/- 0.8 versus
      22.2 +/- 0.8 cm H(2)O; P < 0.01). ASV patients required fewer ventilatory
      settings manipulations (2.4 +/- 0.7 versus 4.0 +/- 0.8 manipulations per patient;
      P < 0.05) and endured less high-inspiratory pressure alarms (0.7 +/- 2.4 versus
      2.9 +/- 3.0; P < 0.05). These results suggest that in this specific population of
      patients, automation of postoperative ventilation with ASV resulted in an outcome
      similar to the control group. The internal logic of the new device resulted in
      less manipulation of the setting and alarms that could simplify respiratory
      management. IMPLICATIONS: Adaptive support ventilation (ASV), a ventilatory mode
      providing automatic adjustment of the settings was compared with standard
      management for rapid tracheal extubation after cardiac surgery. The two
      approaches were equal in terms of outcome. In ASV, we observed fewer ventilator
      settings manipulations and a smaller amount of alarms, suggesting that this
      automatic mode may simplify postoperative respiratory management without delaying
      extubation.

PMID- 14633554
TI  - ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute
      lung injury in rabbits.
AB  - Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS)
      expressed in the lung is thought to play a crucial role in the pathogenesis of
      endotoxin-induced acute lung injury (ALI). In this two-part study, we determined
      whether ONO-1714, a new selective iNOS inhibitor, attenuates endotoxin-induced
      ALI in rabbits. For Part I of the study, a control group received IV saline and
      ALI was induced by IV infusion of endotoxin 5 mg/kg over 30 min in 4 groups.
      Three groups received either 0.1, 0.03, or 0.01 mg/kg of ONO-1714 10 min before
      the start of endotoxin and the fourth group received saline. For Part II of the
      study, ALI was induced by endotoxin infusion in all 6 groups. One group was
      treated with saline. The other 5 groups received ONO-1714 0.1 mg/kg at various
      timings (10 min before or 1, 2, 3, or 4 h after ALI induction). The lungs were
      mechanically ventilated with 40% oxygen for 6 h after induction of ALI. In Part
      I, pretreatment with 0.1 mg/kg ONO-1714 mitigated endotoxin-induced ALI. In Part
      II, early posttreatment (within 2 h after the insult) with ONO-1714 was as
      effective as pretreatment in improving oxygenation, lung mechanics, lung
      leukosequestration, pulmonary edema, and histological change. However, lung
      damage was not improved in rabbits receiving the drug 3 or 4 h after endotoxin.
      These data suggest that the current study is a basis for future clinical trials
      to elucidate whether ONO-1714 can be a promising therapeutic approach in patients
      with acute respiratory distress syndrome induced by endotoxin/sepsis.
      IMPLICATIONS: An excess of nitric oxide is thought to play a crucial role in the
      pathogenesis of acute organ injury in endotoxemia. Early posttreatment with ONO
      1714, a nitric oxide synthase inhibitor, attenuated physiological, biochemical,
      and pathological changes in endotoxin-induced acute lung injury in rabbits.

PMID- 14633555
TI  - The effects of vasopressin on systemic and splanchnic hemodynamics and metabolism
      in endotoxin shock.
AB  - We compared the effects of vasopressin and norepinephrine on systemic and
      splanchnic circulation and metabolism in endotoxin shock in pigs. Twenty-one pigs
      were randomized to endotoxin shock (Escherichia coli endotoxin infusion) (n = 6),
      endotoxin and vasopressin (VASO; n = 6), endotoxin and norepinephrine (NE; n =
      6), and controls (n = 3). Endotoxin infusion was increased to induce hypotension,
      after which vasopressin or norepinephrine was started to keep systemic mean
      arterial blood pressure >70 mm Hg. Regional blood flows and arterial and regional
      lactate concentrations were measured. Tonometers with microdialysis capillaries
      were inserted into the stomach, jejunum, and colon. Systemic mean arterial blood
      pressure >70 mm Hg was achieved in the VASO and NE groups. Vasopressin decreased
      cardiac output, superior mesenteric artery, and portal vein blood flow, whereas
      hepatic arterial blood flow increased. Arterial lactate concentration increased
      from 2.0 mM (1.6-2.1 mM) to 4.7 mM (4.7-4.9 mM) (P = 0.007). Systemic and
      mesenteric oxygen delivery and consumption decreased and oxygen extraction
      increased in the VASO group. Vasopressin increased mucosal-arterial PCO(2)
      gradients in all three locations, whereas luminal lactate release occurred only
      in the jejunum. Animals in the NE group remained stable. Vasopressin reversed
      hypotension but decreased systemic and gut blood flow. This was associated with
      hyperlactatemia, signs of visceral dysoxia, and jejunal luminal lactate release.
      IMPLICATIONS: Although vasopressin induces vasoconstriction in visceral region,
      its effects on splanchnic circulation and metabolism during septic-endotoxin
      shock are still poorly characterized. We evaluated the metabolic and hemodynamic
      effects of vasopressin and norepinephrine within the splanchnic area in porcine
      endotoxin shock.

PMID- 14633556
TI  - Monitoring renal oxygen supply in critically-ill patients using urinary oxygen
      tension.
AB  - Critically-ill patients are at risk of developing renal disorders as a
      consequence of systemic hypoperfusion. Ischemic acute tubular necrosis and
      resulting acute renal failure are caused by hypotension or therapeutic
      management. In this study, we tested the change of O(2) availability induced by
      fenoldopam mesylate using the continuous measurement of urinary oxygen tension
      (PuO(2)), a relatively noninvasive technique that could provide potentially
      important real-time data regarding renal oxygenation in intensive care unit
      patients. Fenoldopam was administered at different doses (0.03, 0.06, and 0.09
      microg x kg(-1) x min(-1)) to 50 stable critically-ill patients. Urine output was
      collected every hour to assess volume and urinary electrolytes. Heart rate, mean
      arterial blood pressure, cardiac output, pulmonary artery occlusion pressure,
      arterial oxygen delivery index, and oxygen consumption index were analyzed after
      fenoldopam dose modifications and at infusion end. PaO(2) and PuO(2) continuous
      measurements were obtained through two sensors inserted in the radial artery and
      in the bladder. After a fenoldopam dose increase, PuO(2) significantly increased
      (P < 0.05), whereas PaO(2) remained unchanged. During the study, heart rate, mean
      arterial blood pressure, cardiac output, central venous pressure, pulmonary
      artery occlusion pressure, arterial oxygen delivery index, and oxygen consumption
      remained unchanged. Dose-dependent PuO(2) increases, unrelated to indexes of
      systemic perfusion and cardiac function, demonstrate that fenoldopam affects the
      balance between renal oxygen supply and demand in stable critically-ill patients.
      IMPLICATIONS: Acute renal failure in critically-ill patients is associated with
      frequent mortality. Prolonged renal hypoperfusion cannot be detected by current
      systemic hemodynamic indexes. Using continuous measurement of urinary oxygen
      tension, which could indirectly provide real-time data regarding renal
      oxygenation, our study showed that fenoldopam increases the ratio between oxygen
      supply and demand.

PMID- 14633557
TI  - The dose-related effects of ketamine on mortality and cytokine responses to
      endotoxin-induced shock in rats.
AB  - In our previous study, ketamine administration was found to inhibit hypotension,
      metabolic acidosis, and cytokine responses in endotoxemia. However, only a few
      studies have indicated whether ketamine has the dose-related beneficial effects
      after endotoxin injection. Our objective was to clarify the dose-related effects
      of ketamine on mortality and cytokine responses to endotoxemia in rats. Sixty
      five rats were divided at random among five equal groups: Group C was given
      saline alone. Group E was given endotoxin alone (Escherichia coli endotoxin; 10
      mg/kg, IV). Group L received a a low dose of ketamine (5 mg.kg(-1).h(-1), IV),
      Group M a medium dose of ketamine (10 mg.kg(-1).h(-1), IV), and Group H a high
      dose of ketamine (20 mg.kg(-1).h(-1), IV), all exposure to endotoxin. After
      endotoxin injection, hemodynamics, acid-base status, mortality rate, and plasma
      concentrations of tumor necrosis factor alpha and interleukin 6 were assessed for
      each of the five groups. Endotoxin injection produced progressive hypotension,
      metabolic acidosis, and a large increase in plasma cytokine concentrations.
      Mortality rates 8 h after endotoxin injection were 0% for group C, 92% for group
      E, 48% for group L, 0% for group M, and 32% for group H. Ketamine administration
      thus clearly had a beneficial effect on mortality rates, with that for group M
      lower than for groups L and H (P < 0.05). The cytokine responses to endotoxin
      were somewhat suppressed in group M but not in group L. Ketamine administration
      dose-independently inhibited hypotension, metabolic acidosis, and cytokine
      responses in rats injected with endotoxin.

PMID- 14633558
TI  - The use of the LMA-ProSeal in airway resuscitation.
AB  - Insufflation of the stomach with air can be a complication of face mask
      ventilation in the case of airway obstruction. Although the laryngeal mask airway
      has proven value in airway resuscitation, it has two major failings: a relatively
      low seal pressure and lack of access to the alimentary tract. A case is reported
      in which failed intubation (by multiple techniques) and intermittent face mask
      ventilation resulted in gastric distension, decreased airway compliance, and
      compromised gas exchange. The patient experience oxyhemoglobin saturation that
      did not improve despite laryngeal mask ventilation. The patient was resuscitated
      with a LMA-ProSeal, which permitted ventilation with high airway pressures.
      Return of oxyhemoglobin saturation occurred after decompression of the stomach
      with a gastric tube inserted via the LMA-ProSeal's gastric drain.

PMID- 14633559
TI  - Kappa-opioid receptor selectivity for ischemic neuroprotection with BRL 52537 in
      rats.
AB  - Kappa-opioid receptors (KOR) have been implicated in neuroprotection from
      ischemic neuronal injury, but less work has been performed with transient focal
      cerebral ischemia to determine the role of KOR during reperfusion. We tested the
      effects of a selective and specific KOR agonist, BRL 52537 hydrochloride [(+/-)-1
      (3,4-dichlorophenyl)acetyl-2-(1-pyrrolidinyl)methylpiperidine], and the standard
      KOR antagonist, nor-binaltorphimine dihydrochloride [nor-BNI; 17,17'
      (dicyclopropylmethyl)-6,6',7,7'-6,6'-imino-7,7'-binorphinan-3,4',14,14'-tetrol],
      on functional and histological outcome after transient focal ischemia in the rat.
      By use of the intraluminal filament technique, halothane-anesthetized adult male
      Wistar rats were subjected to 2 h of middle cerebral artery occlusion confirmed
      by laser Doppler flowmetry. In a blinded, randomized fashion, rats were treated
      with 1). saline (vehicle) 15 min before reperfusion followed by saline at
      reperfusion for 22 h, 2). saline 15 min before reperfusion followed by BRL 52537
      (1 mg x kg(-1) x h(-1)) at reperfusion for 22 h, 3). saline 15 min before
      reperfusion followed by nor-BNI (1 mg x kg(-1) x h(-1)) at reperfusion for 22 h,
      or 4) nor-BNI (1 mg/kg) 15 min before reperfusion followed by BRL 52537 (1 mgx
      kg(-1)x h(-1)) and nor-BNI (1 mg x kg(-1) x h(-1)) at reperfusion for 22 h.
      Infarct volume (percentage of ipsilateral structure) analyzed at 4 days of
      reperfusion was significantly attenuated in saline/BRL 52537 rats (n = 8; cortex,
      10.2% +/- 4.3%; caudoputamen [CP], 23.8% +/- 6.7%) (mean +/- SEM) compared with
      saline/saline treatment (n = 8; cortex, 28.6% +/- 4.9%; CP, 53.3% +/- 5.8%).
      Addition of the specific KOR antagonist nor-BNI to BRL 52537 completely prevented
      the neuroprotection (n = 7; cortex, 28.6% +/- 5.3%; CP, 40.9% +/- 6.2%) conferred
      by BRL 52537. BRL 52537 did not produce postischemic hypothermia. These data
      demonstrate that KORs may provide a therapeutic target during early reperfusion
      after ischemic stroke. IMPLICATIONS: The neuroprotective effect of selective
      kappa-opioid agonists in transient focal ischemia is via a selective action at
      the kappa-opioid receptors.

PMID- 14633560
TI  - Propofol suppresses the cortical somatosensory evoked potential in rats.
AB  - The dose-response curve for the effect of volatile anesthetics on the
      somatosensory evoked potential (SEP) is well described, but for propofol, the
      large dose segment of the curve is undefined. We describe the effect of
      increasing plasma concentrations of propofol on cortical SEPs in 18 rats. After
      surgical preparation under ketamine anesthesia, a remifentanil infusion was begun
      at 2.5, 5, or 10 microg x kg(-1) x min(-1). After 20 min, the propofol infusion
      was initiated at 20 mg x kg(-1) x h(-1) and was increased to 40, 60, and 80 mg x
      kg(-1) x h(-1) at 20-min intervals. SEP was recorded before remifentanil
      infusion, before propofol infusion rate changes, and 30 min after discontinuing
      propofol infusion. In six additional rats, the plasma concentrations of propofol
      after each 20-min infusion were measured using gas chromatography. Remifentanil
      did not have a significant effect, but propofol significantly depressed the SEP
      amplitude and prolonged the latency at infusion rates of 40 mg x kg(-1) x h(-1)
      and more. Propofol's effect was dose-dependent, but even at 80 mg x kg(-1) x h(
      1) with an estimated plasma concentration of 31.6 +/- 3.4 microg/mL (10.8 50%
      effective concentration), a measurable response was present in 44.5% of rats.
      These results suggest that even at large doses, propofol and remifentanil provide
      adequate conditions for SEP monitoring. IMPLICATIONS: Rats demonstrate dose
      dependent somatosensory evoked potential (SEP) suppression with propofol but not
      with remifentanil. However, SEP suppression by 50% occurred only at large (1.5
      EC(50)) concentrations of propofol, and a measurable SEP was present in 8 of 18
      rats, even at 10.8 EC(50).

PMID- 14633561
TI  - Dynamic characteristics of cerebral lipid microemboli: videomicroscopy studies in
      rats.
AB  - Cerebral lipid microemboli (LME) may cause postoperative cognitive dysfunction
      after orthopedic and cardiovascular surgery. In 13 anesthetized rats, we created
      a cranial window to study LME using orthogonal polarization spectral imaging
      videomicroscopy. All rats received 0.2 mL of human marrow fat, obtained from
      surgical waste during arthroplasty, injected into the superior vena cava. Five
      rats died within seconds of this injection, despite resuscitation efforts. Seven
      minutes later, we injected an additional 0.1 mL in 6 of the 8 surviving rats. We
      observed the videomicroscopy for 1 h in all 8 rats. Arterial blood pressure (BP)
      was continuously measured. No LME were observed in the first 7 min (n = 8);
      however, within seconds of the additional 0.1 mL injection, mean BP decreased
      from 79 +/- 31 mm Hg to 28 +/- 12 mm Hg (n = 6; P < 0.02). Epinephrine and
      crystalloid infusion increased BP to 161 +/- 9 mm Hg and 20-100 LME were seen
      within 5 min. LME changed shape and fragmentation, erosion, and streaming
      patterns were noted, with transient arteriolar occlusion (10-220 s). Increasing
      BP resulted in reperfusion of occluded arterioles. No venous LME were noted.
      Postmortem, brain and lung LME were found with no patent foramen ovale. This
      model may be useful in studying cerebral LME. IMPLICATIONS: Marrow lipid may pass
      through the lung during orthopedic surgery, creating cerebral lipid microemboli
      (LME). We created a cranial window in rats to study LME flowing through pial
      cortical vessels. Cerebral LME appeared after resuscitation from hypotension and
      vessel occlusion was transient. This model may be useful in studying cerebral
      LME.

PMID- 14633562
TI  - The effect of right versus left lateral decubitus positions on induction of
      spinal anesthesia for cesarean delivery.
AB  - Induction of spinal anesthesia for cesarean delivery in the left lateral (LL)
      decubitus position combined with intraoperative left uterine displacement may
      result in pooling of local anesthetic onto one side of the body. We studied the
      effect of the right lateral (RL) and LL decubitus positions during placement of
      spinal anesthesia on the intrathecal spread of 0.5% hyperbaric bupivacaine plus
      fentanyl in 60 term parturients. Though all parturients acquired a loss of cold
      sensation at T4 15 min after intrathecal injection, more parturients in the LL
      group than in the RL group did so at 5 min (P < 0.05). The maximum levels of
      sensory blockades, amounts of fluid, vasopressor, and supplementary analgesia
      used, and the incidence of postoperative complications were similar. We conclude
      that the two positions can be used equally well when hyperbaric bupivacaine and
      fentanyl are used in cesarean delivery under spinal anesthesia. IMPLICATIONS: We
      conducted a double-blinded randomized trial comparing the spread of spinal
      anesthesia placed with a parturient in either the right or left lateral position.
      There was a faster onset in the left lateral group; however, the maximum block
      heights and the time taken to achieve them were similar in both groups.

PMID- 14633563
TI  - Ropivacaine and fentanyl concentrations in patient-controlled epidural analgesia
      during labor: a volume-range study.
AB  - We enrolled nulliparous women in induced labor in a randomized study to determine
      whether increasing the concentration of the solution used in a patient-controlled
      epidural analgesia (PCEA) device was required as labor progressed. Patients were
      assigned to 6 groups (n = 25 in each group), receiving ropivacaine/fentanyl in
      concentrations of either 0.1%/0.5 microg/mL or 0.2%/1 microg/mL via a PCEA pump.
      Three groups received boluses of 12, 16, or 20 mL dilute solution in early labor
      (uterine contractions every 3 min and 4-cm cervical dilation) then 6, 8, and 10
      mL concentrated solution in late labor. Three other groups received boluses of
      12, 16, or 20 mL dilute solution during both periods. The lockout interval was 25
      min. The primary outcome was time until the first request for staff-administered
      analgesia supplement. Hourly assessments included pain scores on a visual analog
      scale (VAS) graded from 0 to 10, satisfaction scores, arterial blood pressure,
      motor block intensity, and the upper sensory level of epidural anesthesia.
      Patients, midwives, and the observer were unaware of study solutions and PCEA
      settings. The maximum pain score was defined as the highest score experienced by
      each patient during each period. Duration of analgesia was defined as the time
      from the start of each period to the first injection of rescue analgesia and was
      compared using a survival analysis. There were no differences among the groups
      with regard to demographic and obstetric variables, arterial blood pressure,
      motor block intensity, upper sensory level, or satisfaction scores. At least 75%
      of the women rated their satisfaction as either good or excellent during each
      period. During late labor, the maximum pain score was lower in the group
      receiving 20 mL dilute solution compared with the group receiving 6 mL
      concentrated solution. Maximum pain score was not significantly different between
      20 mL dilute solution and 10 mL concentrated solution (difference between VAS
      values = -0.4; 95% confidence limits, -1.599 and 0.799; P = 0.5055). During late
      labor, the duration of analgesia was longer in groups receiving 20 mL dilute
      solution (99 +/- 4 min) (mean +/- SD) than in those receiving 12 mL (77 +/- 30
      min) and 16 mL (80 +/- 23 min). Duration of analgesia did not differ between
      groups receiving 20 mL and 10 mL (92 +/- 23 min) or between groups receiving 12
      mL and 6 mL (78 +/- 30 min) of each respective solution. Duration of analgesia
      was longer in the groups receiving 8 mL concentrated solution (94 +/- 16 min)
      than in those receiving 16 mL dilute solution. We concluded that 0.1%/0.5
      microg/mL ropivacaine/fentanyl was effective throughout labor when 20 mL was
      injected with each PCEA demand. With 16 mg ropivacaine and 8 microg fentanyl, the
      duration of analgesia was prolonged by doubling the concentration when labor
      became active. When 12 mg ropivacaine and 6 microg fentanyl were injected at each
      demand, analgesia was less satisfactory and doubling the concentration was not
      clinically effective. These results suggest that the effectiveness of PCEA is
      dependent on drug mass rather than the volume or concentration administered with
      each successful pump demand. IMPLICATIONS: There is no clinical reason for
      increasing the concentration of the patient-controlled epidural analgesia (PCEA)
      solution when labor becomes active provided that an effective dose is already
      being administered with each demand. The quality of PCEA depends on the drug mass
      given with each demand rather than the concentration of the pump solution.

PMID- 14633564
TI  - Intraoperative blood salvage during cesarean delivery in a patient with beta
      thalassemia intermedia.
AB  - In this case report, we report a patient with a placenta accreta and thalassemia
      intermedia undergoing cesarean delivery. There are no data regarding the use of
      cell salvage in patients with thalassemia. During the course of her surgery, she
      lost approximately 9000 mL of blood. Of this blood, 2250 mL of concentrated red
      cells were collected, washed, and returned to the patient. During processing,
      increased hemolysis was noted in the effluent line of the cell salvage machine,
      which resolved by increasing the wash volume. The patient's postoperative course
      was uneventful. This case would suggest that cell salvage in patients with
      thalassemia can be performed safely; however, further study is warranted.
      IMPLICATIONS: This case report details the safe administration of cell salvage in
      a patient with beta thalassemia undergoing cesarean delivery. Cell salvage is the
      collection, washing, and re-administration of blood lost during surgery. This
      process has not been previously reported in a patient with this type of blood
      disease.

PMID- 14633565
TI  - Hyperbaric therapy for a postpartum patient with prolonged epidural blockade and
      tomographic evidence of epidural air.
AB  - We used the epidural technique "loss of resistance to air" to provide labor
      analgesia in a healthy parturient. Inadequate analgesia required epidural
      catheter replacement using the same technique. Delayed recovery of sensory and
      motor blockade postpartum necessitated computed tomography and magnetic resonance
      imaging studies. These revealed 4-6 mL of air in the epidural space with no
      evidence of thecal compression. On the advice of the neurologist, this patient
      underwent hyperbaric therapy 14 h after the discontinuation of the epidural
      infusion. The patient made a complete recovery and was discharged without
      neurologic sequelae. It is possible that epidural air delayed the absorption of
      local anesthetics as a result of a reduction in the vascular surface area.
      Although a cause and effect relationship between epidural air and prolonged
      neurological block cannot be categorically established, the use of "loss of
      resistance to air" technique complicated the differential diagnosis.
      IMPLICATIONS: We report a case of prolonged motor and sensory block after labor
      analgesia using "loss of resistance to air" technique. The presence of epidural
      air on tomography resulted in the patient undergoing hyperbaric therapy. The use
      of loss of resistance to air technique complicated the differential diagnosis of
      prolonged sensory and motor block.

PMID- 14633566
TI  - Thoracic epidural anesthesia increases tissue oxygenation during major abdominal
      surgery.
AB  - Intraoperative surgical stress may markedly increase adrenergic nerve activity
      and plasma catecholamine concentrations, which causes peripheral vasoconstriction
      and decreased tissue oxygen partial pressure possibly leading to tissue hypoxia.
      Tissue hypoxia is associated with an increased incidence of surgical wound
      infections. Thoracic epidural anesthesia blocks afferent neural stimuli and
      inhibits efferent sympathetic outflow in response to painful stimuli.
      Consequently, we tested the hypothesis that supplemental thoracic epidural
      anesthesia during major abdominal surgery improves tissue perfusion and
      subcutaneous oxygen tension. Thirty patients were randomly assigned to two
      groups: general (n = 15) or combined general and epidural anesthesia (n = 15).
      Anesthesia technique and fluid management were standardized. Subcutaneous tissue
      oxygen tension was measured continuously in the upper arm with a Clark type
      electrode. Data were compared with unpaired, two-tailed t-tests, Wilcoxon's
      ranked sum test, or repeated-measures analysis of variance and Scheffe F tests as
      appropriate; P < 0.05 was considered statistically significant. After 60 min,
      intraoperative tissue oxygen tension was significantly larger during combined
      anesthesia than during general anesthesia (54.3 +/- 7.4 mm Hg versus 42.1 +/- 8.6
      mm Hg; P = 0.0002). Subcutaneous tissue oxygen tension remained significantly
      higher in the combined general/epidural anesthesia group throughout the
      observation period. Hemodynamic responses and global oxygen variables were
      similar in the groups. Thoracic epidural anesthesia improved intraoperative
      tissue oxygen tension outside the area of the epidural block. Thus, our results
      give evidence that supplemental neural nociceptive block blunts generalized
      vasoconstriction caused by surgical stress and adrenergic responses.
      IMPLICATIONS: Thoracic epidural anesthesia blunts the decrease of subcutaneous
      tissue oxygen tension caused by surgical stress and adrenergic vasoconstriction
      during major abdominal surgery. Consequently, combined general and epidural
      anesthesia helps to provide sufficient tissue oxygenation.

PMID- 14633567
TI  - The difference between intramural and arterial partial pressure of carbon dioxide
      increases significantly during laparoscopic cholecystectomy: the effect of
      thoracic epidural anesthesia.
AB  - We studied the effects of pneumoperitoneum on gastric submucosal perfusion
      metabolism during elective laparoscopic cholecystectomy (LASC) by measuring the
      PCO(2) gap, defined as the difference between intramucosal PCO(2) and arterial
      PCO(2), using gas tonometry in 20 patients. Furthermore, we examined whether
      thoracic epidural anesthesia (TEA) affects gastric submucosal perfusion
      metabolism during LASC. Patients were randomly allocated to receive general
      anesthesia (group G, n = 10) or general anesthesia combined with TEA (group E, n
      = 10). In both groups, the PCO(2) gap increased significantly during
      pneumoperitoneum and remained at this level until the end of surgery compared
      with the baseline value. There were no significant differences in PCO(2) gap
      values between the two groups at any time sampled. These results suggested that
      pneumoperitoneum significantly impaired gastric submucosal perfusion and
      metabolism and that TEA did not attenuate the impairment of gastric submucosal
      perfusion during or after pneumoperitoneum. IMPLICATIONS: We investigated the
      effect of pneumoperitoneum on gastric submucosal perfusion by measuring PCO(2)
      gap with the use of gas tonometry. PCO(2) gap significantly increased during and
      after the pneumoperitoneum compared with the control level. Thoracic epidural
      anesthesia did not attenuate this inhibition.

PMID- 14633568
TI  - The effects of thoracic epidural anesthesia on hepatic perfusion and oxygenation
      in healthy pigs during general anesthesia and surgical stress.
AB  - Perioperative liver injury due to decreased perfusion may be an underlying
      mechanism behind the development of systemic inflammatory response syndrome. We
      designed this animal study to assess whether thoracic epidural anesthesia (TEA)
      impairs liver oxygenation due to induced hypotension. After ethical approval, 19
      anesthetized and acutely instrumented pigs were randomly assigned to 3 groups
      (control and TEA alone versus TEA plus volume loading). Bupivacaine 0.5% 0.75 mL
      per segment was injected into the epidural space, aiming for a T5 to T12 block.
      After baseline values were obtained, measurements were repeated 60 and 120 min
      after epidural injection. TEA was associated with decreased mean arterial blood
      pressure but no change in total hepatic blood flow. Oxygen delivery to the liver
      and oxygen uptake remained unchanged. Liver tissue oxygen partial pressure did
      not decrease. The plasma indocyanine green disappearance rate remained stable.
      Volume loading before TEA did not relevantly affect total hepatic blood flow; it
      even decreased oxygen supply to the liver by hemodilution. We conclude that,
      despite decreased mean arterial blood pressure, TEA did not affect liver
      oxygenation. There was no clinically relevant effect of volume loading on total
      hepatic perfusion.

PMID- 14633569
TI  - Fatal gas embolism during transurethral incision of the bladder neck under spinal
      anesthesia.
AB  - We report a case of fatal gas embolism during transurethral incision of the
      bladder neck under spinal anesthesia in a 76-yr-old man. We confirmed the
      diagnosis of venous gas embolism by aspiration of frothy blood through the double
      lumen central venous catheter and by observation on the transesophageal
      echocardiogram of a massive gas embolism in the right atrium and right ventricle
      with obstruction of right ventricle outflow. This report is presented in an
      attempt to remind anesthesiologists of this unusual but potentially fatal
      complication that may occur during common transurethral surgery. IMPLICATIONS: We
      report a patient undergoing transurethral incision of the bladder neck who
      developed a fatal gas embolism. This report is presented in an attempt to remind
      anesthesiologists of this unusual but potentially fatal complication that may
      occur during common transurethral surgery.

PMID- 14633570
TI  - Prevention of atelectasis formation during induction of general anesthesia.
AB  - General anesthesia promotes atelectasis formation, which is augmented by
      administration of large oxygen concentrations. We studied the efficacy of
      positive end-expiratory pressure (PEEP) application during the induction of
      general anesthesia (fraction of inspired oxygen [FIO(2)] 1.0) to prevent
      atelectasis. Sixteen adult patients were randomly assigned to one of two groups.
      Both groups breathed 100% O(2) for 5 min and, after a general anesthesia
      induction, mechanical ventilation via a face mask with a FIO(2) of 1.0 for
      another 5 min before endotracheal intubation. Patients in the first group (PEEP
      group) had continuous positive airway pressure (CPAP) (6 cm H(2)O) and mechanical
      ventilation via a face mask with a PEEP of 6 cm H(2)O. No CPAP or PEEP was
      applied in the control group. Atelectasis, determined by computed radiograph
      tomography, and analysis of blood gases were measured twice: before the beginning
      of anesthesia and directly after the intubation. There was no difference between
      groups before the anesthesia induction. After endotracheal intubation, patients
      in the control group showed an increase of the mean area of atelectasis from 0.8%
      +/- 0.9% to 4.1% +/- 2.0% (P = 0.0002), whereas the patients of the PEEP group
      showed no change (0.5% +/- 0.6% versus 0.4% +/- 0.7%). After the intubation with
      a FIO(2) of 1.0, PaO(2) was significantly higher in the PEEP group than in the
      control (591 +/- 54 mm Hg versus 457 +/- 99 mm Hg; P = 0.005). Atelectasis
      formation is prevented by application of PEEP during the anesthesia induction
      despite the use of large oxygen concentrations, resulting in improved
      oxygenation. IMPLICATIONS: Application of positive end-expiratory pressure during
      the induction of general anesthesia prevents atelectasis formation. Furthermore,
      it improves oxygenation and probably increases the margin of safety before
      intubation. Therefore, this technique should be considered for all anesthesia
      induction, at least in patients at risk of difficult airway management during the
      anesthesia induction.

PMID- 14633571
TI  - Validation of an original mathematical model of CO(2) elimination and dead space
      ventilation.
AB  - We present an original, mathematical model of ventilation and gas-exchange. Our
      aim was to validate it using data from previous clinical investigations, allowing
      our use of it in future investigations. The first previous investigation used a
      low-dead space, double-lumen, tracheal tube (DLT). We matched the model's PaCO(2)
      and airway pressures (P(AW)) to the patient mean during use of the DLT and a
      single-lumen tube (SLT). The model's resulting PaCO(2), PECO(2) and P(AW) were
      compared with the patients' as tidal volume (VT) changed with constant minute
      volume. The second investigation examined dead space during anesthesia. The
      model's VT, respiratory rate, CO(2) production, temperature, and alveolar and
      anatomical dead spaces were matched to each mechanically ventilated subject. Bias
      and precision in predictions of PaCO(2) and PECO(2) were calculated. The model's
      bias in prediction of dead space reduction by the DLT was 6.9%. Bias in
      prediction of P(AW) was 0.1% (peak) and -5.13% (mean), of PaCO(2) was 1.2% (DLT)
      and 1.5% (SLT) and of PECO(2) was 1.7% (DLT) and 1.3% (SLT). Prediction of
      PaCO(2) and PECO(2) in the second investigation (as 95% confidence interval of
      bias): PaCO(2) -2.6% to 0.8% and PECO(2) -4.9% to 1.2%. This validation allows
      future application of our model in appropriate theoretical investigations.
      IMPLICATIONS: We present an original, mathematical model of ventilation and gas
      exchange. We validate it against previously published clinical data to allow its
      use in future theoretical investigations where data may be unavailable from
      patients.

PMID- 14633572
TI  - Estimating alveolar dead space from the arterial to end-tidal CO(2) gradient: a
      modeling analysis.
AB  - Using an original, validated, high-fidelity model of pulmonary physiology, we
      compared the arterial to end-tidal CO(2) gradient divided by the arterial CO(2)
      tension (Pa-E'CO(2)/PaCO(2)) with alveolar dead space expressed as a fraction of
      alveolar tidal volume, calculated in the conventional manner using Fowler's
      technique and the Bohr equation: (VDalv/VTalv)(Bohr-Fowler). We examined the
      variability of Pa-E'CO(2)/PaCO(2) and of (VDalv/VTalv)(Bohr-Fowler) in the
      presence of three ventilation-perfusion defects while varying CO(2) production
      (Vdot;CO(2)), venous admixture, and anatomical dead space fraction (VDanat). Pa
      E'CO(2)/PaCO(2) was approximately 59.5% of (VDalv/VTalv)(Bohr-Fowler). During
      constant alveolar configuration, the factors examined (Vdot;CO(2), pulmonary
      shunt fraction, and VDanat) each caused variation in (VDalv/VTalv)(Bohr-Fowler)
      and in Pa-E'CO(2)/PaCO(2). Induced variation was slightly larger for Pa
      E'CO(2)/PaCO(2) during changes in VDanat, but was similar during variation of
      venous admixture and Vdot;CO(2). Pa-E'CO(2)/PaCO(2) may be a useful serial
      measurement in the critically ill patient because all the necessary data are
      easily obtained and calculation is significantly simpler than for
      (VDalv/VTalv)(Bohr-Fowler). IMPLICATIONS: Using an original, validated, high
      fidelity model of pulmonary physiology, we have demonstrated that the arterial to
      end-tidal carbon dioxide pressure gradient may be used to robustly and accurately
      quantify alveolar dead space. After clinical validation, its use could replace
      that of conventionally calculated alveolar dead space fraction, particularly in
      the critically ill.

PMID- 14633573
TI  - Nasolacrimal duct probing in infants and children: an easy technique for
      administering general anesthesia.

PMID- 14633574
TI  - CO(2) removal: a concern with new anesthesia machines.

PMID- 14633575
TI  - Should local anesthetic allergy testing be routinely performed during pregnancy?

PMID- 14633576
TI  - Inadequate tidal volume: asymmetric endotracheal tube cuff inflation resulting in
      a massive persistent airway leak.

PMID- 14633577
TI  - Mutism as a complication of total intravenous anesthesia by propofol.

PMID- 14633578
TI  - Perioperative pulmonary embolism.

PMID- 14633579
TI  - Spinal anesthesia in a patient with neurofibromatosis.

PMID- 14633580
TI  - Sternectomy after cardiac surgery: noncardiac surgery?

PMID- 14633581
TI  - Unique anesthetic management of a patient with a large tracheoesophageal fistula
      using fiberoptic bronchoscopy.

PMID- 14633582
TI  - Is there rationale to use an antiemetic in the same class for the treatment of
      patients who experience postoperative nausea and vomiting despite prophylaxis?

PMID- 14633583
TI  - Oversized endotracheal tube in pediatric anesthesia practice: its objective
      detection.

PMID- 14633584
TI  - Regional anesthesia: another use for the ultrasound vessel finder.

PMID- 14633585
TI  - Presence of a foreign substance in anesthesia machines.

PMID- 14633587
TI  - The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is
      a tool in surgical pathology.
AB  - Cell adhesion receptors (CAMs) are actively involved in regulating various cell
      processes, including growth, differentiation, and cell death. Therefore, CAMs
      represent a large group of morphoregulating molecules, mediating cross-talk
      between cells and of cells with their environment. From this perspective, CAMs do
      contribute to cells and tissue organization, and in diseased tissue, to the
      disease development and biological characteristics. Therefore, observed changes
      in expression patterns of adhesion molecules may contribute to establish a
      diagnosis. A distinct shift in expression patterns in neoplastic epithelium has
      been described, for example for cadherins, integrins, and CD44. A relatively
      novel cell CAM, Ep-CAM, was first reported to be a pan-carcinoma antigen,
      although it is rather a marker of epithelial lineage. Several antibodies directed
      to Ep-CAM have been generated, and many epithelial tissues and their neoplastic
      appendages have been studied. This article outlines the results of these studies.
      Based on the results of these studies, we conclude that Ep-CAM
      immunohistochemistry can be a useful tool in the diagnosis of disturbed
      epithelial tissues.

PMID- 14633588
TI  - NKX3.1 expression is lost in testicular germ cell tumors.
AB  - NKX3.1 is a homeobox gene which exhibits prostate and testis specific expression.
      Loss of NKX3.1 expression has been implicated in prostate development and
      tumorigenesis, but the role of NKX3.1 in testis biology is not known. Here we
      show that NKX3.1 expression is dramatically down-regulated in testicular cancer
      of germ cell origin. Immunohistochemical analysis on a tissue microarray
      containing 510 testicular tissue samples indicate that NKX3.1 is expressed at
      high levels in normal germ cells and in carcinoma in situ, but is sharply
      decreased or absent in most seminomas and all embryonal carcinomas. However,
      NKX3.1 is expressed in a subset of the more differentiated nonseminomas. We
      provide evidence that these changes in NKX3.1 protein levels are mainly due to
      transcriptional effects. These results suggest that NKX3.1 is essential for
      normal testis function and that its loss of expression is highly associated with
      the invasive phenotype of testicular germ cell tumors.

PMID- 14633589
TI  - Association of aortic atherosclerosis with cerebral beta-amyloidosis and learning
      deficits in a mouse model of Alzheimer's disease.
AB  - High fat/high cholesterol diets exacerbate beta-amyloidosis in mouse models of
      Alzheimer's disease (AD). It has been impossible, however, to study the
      relationship between atherosclerosis and beta-amyloidosis in those models because
      such mice were on atherosclerosis-resistant genetic backgrounds. Here we report
      the establishment of AD model mice, B6Tg2576, that are prone to atherosclerosis.
      B6Tg2576 mice were produced by back-crossing Tg2576 mice, an AD mouse model
      overexpressing human amyloid beta-protein precursor with the Swedish double
      mutation, to C57BL/6 mice, a strain susceptible to diet-induced atherosclerosis.
      An atherogenic diet induced aortic atherosclerosis and exacerbated cerebral beta
      amyloidosis in B6Tg2576 mice. Compared with age-matched non-transgenic
      littermates, B6Tg2576 mice developed significantly more diet-induced aortic
      atherosclerosis. Unexpectedly, normal diet-fed B6Tg2576 mice also developed fatty
      streak lesions (early atherosclerosis) in the aorta. The aortic atherosclerotic
      lesion area positively correlated with cerebral beta-amyloid deposits in B6Tg2576
      mice on both atherogenic and normal diets. Furthermore, behavioral assessments
      demonstrated that B6Tg2576 mice fed an atherogenic diet had more spatial learning
      impairment than those fed a normal diet. Our results suggest that synergistic
      mechanisms may be involved in the pathogenesis of atherosclerosis and AD. These
      findings may have important implications in the prevention and treatment of
      cardiovascular diseases as well as AD.

PMID- 14633590
TI  - A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated
      antigen 1, is induced by the Ewing's sarcoma-Wilms' tumor 1 fusion protein of
      desmoplastic small round-cell tumor.
AB  - Recurrent chromosomal translocations in neoplasms often generate hybrid genes
      that play critical roles in tumorigenesis. Desmoplastic small round-cell tumor
      (DSRCT) is an aggressive malignancy associated with the chromosomal translocation
      t(11;22)(p13;q12). This translocation generates a chimeric transcription factor,
      EWS-WT1, which consists of the transcriptional activation domain of the Ewing's
      sarcoma (EWS) protein and the DNA binding domain of the Wilms' tumor 1 (WT1)
      protein. One of the splice variants, EWS-WT1(-KTS) lacks three amino acid
      residues (Lys-Thr-Ser) in the DNA binding domain and transforms NIH3T3 cells.
      Therefore, it is likely that aberrant gene expression caused by EWS-WT1(-KTS) is
      involved in the malignant phenotype of DSRCT. Microarray analysis of 9600 human
      genes revealed that a gene encoding a tetraspanin-family protein, T-cell acute
      lymphoblastic leukemia-associated antigen 1 (TALLA-1), was induced in EWS-WT1(
      KTS)-expressing cell clones. This induction was EWS-WT1(-KTS)-specific, and more
      importantly, TALLA-1 protein was expressed in the three independent cases of
      DSRCT. Tetraspanin-family genes encode transmembrane proteins that regulate
      various cell processes such as cell adhesion, migration and metastasis. Our
      findings provide a novel insight into the malignant phenotype of DSRCT,
      suggesting that TALLA-1 is a useful marker for diagnosis and a potential target
      for the therapy of DSRCT.

PMID- 14633591
TI  - Hedgehog signaling regulates sebaceous gland development.
AB  - Epithelial progenitor cells in skin give rise to multiple lineages, comprising
      the hair follicle, an associated sebaceous gland, and overlying epidermis;
      however, the signals that regulate sebocyte development are poorly understood. We
      tested the potential involvement of the Hedgehog pathway in sebaceous gland
      development using transgenes designed to either block or stimulate Hedgehog
      signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog
      pathway selectively suppressed sebocyte development, Hedgehog pathway activation
      led to a striking increase both in size and number of sebaceous glands.
      Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous
      glands from footpad epidermis, in regions normally devoid of hair follicles and
      associated structures. These ectopic sebaceous glands expressed molecular markers
      of sebocyte differentiation and were functional, secreting their contents
      directly onto the skin's surface instead of into a hair canal. The Hedgehog
      pathway thus plays a key role in sebocyte cell fate decisions and is a potential
      target for treatment of skin disorders linked to abnormal sebaceous gland
      function, such as acne.

PMID- 14633592
TI  - Latent herpesvirus infection in human trigeminal ganglia causes chronic immune
      response.
AB  - The majority of trigeminal ganglia (TGs) are latently infected with alpha
      herpesviruses [herpes simplex virus type-1 (HSV-1) and varicella-zoster virus
      (VZV)]. Whereas HSV-1 periodically reactivates in the TGs, VZV reactivates very
      rarely. The goal of this study was to determine whether herpesvirus latency is
      linked to a local immune cell infiltration in human TGs. T cells positive for the
      CD3 and CD8 markers, and CD68-positive macrophages were found in 30 of 42
      examined TGs from 21 healthy individuals. The presence of immune cells correlated
      constantly with the occurrence of the HSV-1 latency-associated transcript (LAT)
      and only irregularly with the presence of latent VZV protein. In contrast,
      uninfected TGs showed no immune cell infiltration. Quantitative RT-PCR revealed
      that CD8, interferon-gamma, tumor necrosis factor-alpha, IP-10, and RANTES
      transcripts were significantly induced in TGs latently infected with HSV-1 but
      not in uninfected TGs. The persisting lymphocytic cell infiltration and the
      elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for the
      first time that latent herpesviral infection in humans is accompanied by a
      chronic inflammatory process at an immunoprivileged site but without any neuronal
      destruction. The chronic immune response seems to maintain viral latency and
      influence viral reactivation.

PMID- 14633593
TI  - Absence of human papillomavirus in tonsillar squamous cell carcinomas from
      Chinese patients.
AB  - Epidemiological and experimental evidence from Western countries now consistently
      support an etiological role for human papillomavirus (HPV) in a subset of
      oropharyngeal squamous cell carcinomas (SCC), especially those originating in the
      tonsil. The role of HPV in the etiology of tonsil cancer in developing countries
      such as China has not been investigated. In this study, none of 16 tonsil cancer
      specimens from Chinese patients were positive for HPV DNA, whereas those from
      Australian patients using the same methodology gave a positivity rate of 46%. The
      tumors from Chinese patients, like the Australian HPV-negative subset,
      significantly overexpressed pRb and cyclin D1 and underexpressed p16(INK4A)
      (p16). In contrast, the Australian HPV-positive cancers overexpressed p16 and had
      reduced expression of pRb and cyclin D1. These findings may help explain why
      China has a relatively low rate of oropharyngeal cancer compared with Australia.
      They also support the hypothesis that molecular pathways to tonsil cancer
      mediated by HPV are distinct from those induced by mutagens present in cigarette
      smoke or alcohol.

PMID- 14633594
TI  - Liver gene expression profiles of rats treated with clofibric acid: comparison of
      whole liver and laser capture microdissected liver.
AB  - Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the
      peroxisome proliferator activated receptor alpha, leading to hepatocarcinogenesis
      in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first
      transforming normal liver cells into foci. The combination of laser capture
      microdissection (LCM) and genomics has the potential to provide expression
      profiles from such small cell clusters, giving an opportunity to understand the
      process of cancer development in response to PPs. To our knowledge, this is the
      first evaluation of the impact of the successive steps of LCM procedure on gene
      expression profiling by comparing profiles from LCM samples to those obtained
      with non-microdissected liver samples collected after a 1 month CLO treatment in
      the rat. We showed that hematoxylin and eosin (H&E) staining and laser
      microdissection itself do not impact on RNA quality. However, the overall process
      of the LCM procedure affects the RNA quality, resulting in a bias in the gene
      profiles. Nonetheless, this bias did not prevent accurate determination of a CLO
      specific molecular signature. Thus, gene-profiling analysis of microdissected
      foci, identified by H&E staining may provide insight into the mechanisms
      underlying non-genotoxic hepatocarcinogenesis in the rat by allowing
      identification of specific genes that are regulated by CLO in early pre
      neoplastic foci.

PMID- 14633595
TI  - Reconstructed beta-catenin/TCF4 signaling in yeast applicable to functional
      evaluation of APC mutations.
AB  - In human genetics and molecular oncology, mutation research is necessary not only
      to identify mutations in nucleic acid sequences, but also to analyze the loss of
      function caused by mutant proteins. We reconstructed a protein-protein network
      system of human beta-catenin and TCF4, in Saccharomyces cerevisiae. beta-Catenin
      and TCF4 proteins form a complex and transactivate reporter genes. Co-expressed
      wild-type APC with beta-catenin and TCF4 inhibit the transcriptional activity of
      the beta-catenin/TCF4 complex in yeast, as well as in mammals. This unique method
      in which the beta-catenin/TCF4 signaling pathway is reconstructed in vivo may
      prove useful for the functional evaluation of APC mutants, including a type of
      APC truncated and missense mutants influenced to the ability of binding to beta
      catenin.

PMID- 14633596
TI  - Implantation-dependent expression of trophinin by maternal fallopian tube
      epithelia during tubal pregnancies: possible role of human chorionic
      gonadotrophin on ectopic pregnancy.
AB  - Trophinin, tastin, and bystin have been identified as molecules potentially
      involved in human embryo implantation. Both trophoblasts and endometrial
      epithelial cells express trophinin, which mediates apical cell adhesion through
      homophilic trophinin-trophinin binding. We hypothesized that trophinin's function
      in embryo implantation is unique to humans and investigated the expression of
      trophinin, tastin, and bystin in ectopic pregnancy, a condition unique to humans.
      In tubal pregnancies, high levels of all three were found in both trophoblasts
      and fallopian tubal epithelia. Trophinin expression in maternal cells was
      particularly high in the area adjacent to the trophoblasts, whereas trophinin was
      barely detectable in intact fallopian tubes from women with in utero pregnancies
      or without pregnancies. When explants of intact fallopian tube were incubated
      with the human chorionic gonadotrophin (hCG), trophinin expression was enhanced
      in epithelial cells. Since the trophectoderm of the human blastocyst secretes hCG
      before and after implantation, these results suggest that hCG from the human
      embryo induces trophinin expression by maternal cells. As both beta-subunit of
      hCG and trophinin genes have diverged in mammals, the present study suggests a
      unique role of hCG and trophinin in human embryo implantation, including the
      pathogenesis of ectopic pregnancy.

PMID- 14633597
TI  - Infiltration of neutrophils is required for acquisition of metastatic phenotype
      of benign murine fibrosarcoma cells: implication of inflammation-associated
      carcinogenesis and tumor progression.
AB  - QR-32 tumor cells, a clone derived from a murine fibrosarcoma, are poorly
      tumorigenic and nonmetastatic when injected into syngeneic C57BL/6 mice. However,
      they are converted to highly malignant ones once they have grown in vivo after
      being co-implanted in a subcutaneous site with a foreign body, a gelatin sponge.
      Early phase of inflammation induced by the gelatin sponge participates in the
      conversion and histological analysis shows predominant infiltration of
      neutrophils. The objective of this study was to determine whether the depletion
      of the infiltrating neutrophils has any effect on the tumor progression.
      Intraperitoneal administration of a monoclonal anti-granulocyte antibody, RB6-8C5
      (RB6), depleted neutrophils from both the peripheral blood circulation and the
      local inflamed site in mice with co-implantation of QR-32 tumor cells and gelatin
      sponge. The RB6 administration did not inhibit either tumor development or growth
      of QR-32 tumor cells. In contrast, tumor cell lines established from RB6
      administered mice showed a significant decrease in metastatic incidence as
      compared with the tumor cell lines obtained from the mice with administration of
      control rat IgG or saline. Metastatic ability was significantly suppressed when
      RB6 had been administered in the early phase (from day -2 to day 6 after
      implantation); however, the administration in the middle (from day 6 to day 14)
      or late (from day 14 to day 22) phase did not affect the metastatic ability. We
      confirmed the phenomena by using integrin beta(2) knockout mice that had impaired
      neutrophil infiltration into inflamed sites. In the knockout mice, neutrophils
      hardly infiltrated into the gelatin sponge and the tumors showed dramatically
      suppressed metastatic phenotype as compared with those in wild-type mice or nude
      mice. Immunohistochemical analysis demonstrated that expressions of 8-hydroxy-2'
      deoxyguanosine and nitrotyrosine were parallel to those in the presence of
      neutrophils. These results suggested that inflammation, especially when
      neutrophils infiltrate into tumor tissue, is primarily important for benign tumor
      cells to acquire metastatic phenotype.

PMID- 14633598
TI  - B lymphocyte-specific c-Myc expression stimulates early and functional expansion
      of the vasculature and lymphatics during lymphomagenesis.
AB  - Expression of the c-myc proto-oncogene is deregulated in many human cancers. We
      examined the role of c-Myc in stimulating angiogenesis and lymphangiogenesis in a
      highly metastatic murine model of Burkitt's lymphoma (E micro -c-myc), where c
      Myc is expressed exclusively in B lymphocytes. Immunohistochemical analysis of
      bone marrow and lymph nodes from young (preneoplastic) E micro -c-myc transgenic
      mice revealed increased growth of blood vessels, which are functional by dye flow
      assay. Lymphatic sinuses also increased in size and number within the lymph
      nodes, as demonstrated by immunostaining for with a lymphatic endothelial marker
      10.1.1. The 10.1.1 antibody recognizes VEGFR-2- and VEGFR-3-positive lymphatic
      sinuses and vessels within lymph nodes, and also recognizes lymphatic vessels in
      other tissues. Subcutaneously injected dye traveled more efficiently through
      draining lymph nodes in E micro -c-myc mice, indicating that these hypertrophic
      lymphatic sinuses increase lymph flow. Purified B lymphocytes and lymphoid
      tissues from E micro -c-myc mice expressed increased levels of vascular
      endothelial growth factor (VEGF) by immunohistochemical or immunoblot assays,
      which could promote blood and lymphatic vessel growth through interaction with
      VEGFR-2, which is expressed on the endothelium of both vessel types. These
      results indicate that constitutive c-Myc expression stimulates angiogenesis and
      lymphangiogenesis, which may promote the rapid growth and metastasis of c-Myc
      expressing cancer cells, respectively.

PMID- 14633599
TI  - Interference with transforming growth factor-beta/ Smad3 signaling results in
      accelerated healing of wounds in previously irradiated skin.
AB  - Transforming growth factor (TGF)-beta regulates many aspects of wound repair
      including inflammation, chemotaxis, and deposition of extracellular matrix. We
      previously showed that epithelialization of incisional wounds is accelerated in
      mice null for Smad3, a key cytoplasmic mediator of TGF-beta signaling. Here, we
      investigated the effects of loss of Smad3 on healing of wounds in skin previously
      exposed to ionizing radiation, in which scarring fibrosis complicates healing.
      Cutaneous wounds made in Smad3-null mice 6 weeks after irradiation showed
      decreased wound widths, enhanced epithelialization, and reduced numbers of
      neutrophils and myofibroblasts compared to wounds in irradiated wild-type
      littermates. Differences in breaking strength of wild-type and Smad3-null wounds
      were not significant. As shown previously for neutrophils, chemotaxis of primary
      dermal fibroblasts to TGF-beta required Smad3, but differentiation of fibroblasts
      to myofibroblasts by TGF-beta was independent of Smad3. Previous irradiation
      enhanced induction of connective tissue growth factor mRNA in wild-type, but not
      Smad3-null fibroblasts, suggested that this may contribute to the heightened
      scarring in irradiated wild-type skin as demonstrated by Picrosirius red
      staining. Overall, the data suggest that attenuation of Smad3 signaling might
      improve the healing of wounds in previously irradiated skin commensurate with an
      inhibition of fibrosis.

PMID- 14633600
TI  - Successful immortalization of endometrial glandular cells with normal structural
      and functional characteristics.
AB  - The human endometrium is a dynamic tissue, the proliferative activity of which
      dramatically changes throughout the menstrual cycle, with exquisite regulation by
      sex-steroid hormones. Primary endometrial epithelial cells fall into senescence
      within 2 weeks when cultured on plastic dishes, and more complete understanding
      of endometrial biology has been delayed because of, in part, a lack of an in
      vitro culture model for endometrial epithelial cells. Our goal was to establish
      immortalized human endometrial glandular cells that retain the normal functions
      and characteristics of the primary cells. Because the Rb/p16 and p53 pathways are
      known to be critical elements of epithelial senescence in early passages, we used
      human papillomavirus E6/E7 to target these pathways. The combination of human
      papillomavirus-16 E6/E7 expression and telomerase activation by the introduction
      of human telomerase reverse transcriptase (hTERT) led to successful
      immortalization of the endometrial glandular cells. E6/E7 expression alone was
      sufficient to extend their life span more than 20 population doublings, but the
      telomerase activation was further required to enable the cells to pass through
      the subsequent replicative senescence at 40 population doublings. Isolated
      immortalized cells contained no chromosomal abnormalities or only nonclonal
      aberrations, retained responsiveness to sex-steroid hormones, exhibited glandular
      structure on three-dimensional culture, and lacked transformed phenotypes on soft
      agar or in nude mice. These findings support the notion that both Rb
      inactivation/p53 inactivation and telomerase activation are necessary to
      immortalize endometrial epithelial cells, but additional factors are required for
      endometrial carcinogenesis. Our established cell lines show great promise for
      investigation of hormone functions, endometrial biology, and endometrial
      carcinogenesis.

PMID- 14633601
TI  - High-level expression of EphA2 receptor tyrosine kinase in prostatic
      intraepithelial neoplasia.
AB  - EphA2 is a transmembrane receptor tyrosine kinase that is overexpressed in many
      carcinomas. Specific targeting of EphA2 with monoclonal antibodies is sufficient
      to inhibit the growth, migration and invasiveness of aggressive cancers in animal
      models. Using immunohistochemical analyses, we measured the expression of EphA2
      in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and
      adjacent benign prostate tissue from ninety-three radical prostatectomy
      specimens. These results were related to multiple clinical and
      pathologicalcharacteristics. The fraction of cells staining positively with EphA2
      in benign prostatic epithelium (mean, 12%) was significantly lower than that in
      high-grade prostatic intraepithelial neoplasia (mean, 67%, P < 0.001) and
      prostatic adenocarcinoma (mean, 85%, P < 0.001). Moreover, the intensity of EphA2
      immunoreactivity in prostatic adenocarcinoma was significantly higher than in
      benign prostatic tissue (P < 0.001) or high-grade prostatic intraepithelial
      neoplasia (P < 0.001). Benign prostatic epithelium showed weak or no
      immunoreactivity for EphA2 in all cases examined. Whereas EphA2 immunoreactivity
      related to neoplastic transformation, it did not correlate with other clinical
      and pathological parameters examined. Our data suggest that EphA2 levels increase
      as prostatic epithelial cells progress toward a more aggressive phenotype.
      Progressively higher levels of EphA2 in high-grade prostatic intraepithelial
      neoplasia and prostatic carcinoma are consistent with recent evidence that EphA2
      functions as a powerful oncogene. Moreover, the presence of high levels of EphA2
      in these cells suggests opportunities for prostate cancer prevention and
      treatment.

PMID- 14633602
TI  - Alterations of beta-catenin pathway in non-melanoma skin tumors: loss of alpha
      ABC nuclear reactivity correlates with the presence of beta-catenin gene
      mutation.
AB  - To determine the role of beta-catenin pathway in human skin carcinogenesis, 135
      non-melanoma skin tumors were analyzed for beta-catenin expression and gene
      mutations. Intense nucleo-cytoplasmic immunoreactivity for C terminus beta
      catenin antibodies was observed in all pilomatricomas and in single cases of
      trichoepithelioma and squamous cell carcinoma showing peculiar signs of matrical
      differentiation. Moderate increase of beta-catenin nuclear staining was detected
      in a significant proportion of basal cell carcinomas, Bowen disease,
      spiroadenomas, and occasionally also in squamous cell carcinomas, but in these
      neoplasms only a limited fraction of tumor cells accumulated beta-catenin.
      Molecular analysis revealed that beta-catenin gene mutations are a peculiar
      feature of skin tumors with matrical differentiation and correlate with a pattern
      of intense and diffuse beta-catenin nuclear expression. In contrast, adenomatous
      polyposis coli (APC) and AXIN2 mutations were not involved in skin tumorigenesis.
      Analysis of Wnt pathway revealed that TCF-1 and MITF-M were selectively induced
      in the tumor types harboring beta-catenin mutations, indicating that a Wnt/beta
      catenin pathway involving TCF-1 and MITF-M is activated in these tumors.
      Interestingly, high expression levels of TCF-3 were found in basal cell
      carcinomas and spiroadenomas. TCF-3 is reported to act as a negative modulator of
      beta-catenin degradation pathway. Thus, the moderate increase of beta-catenin
      nuclear staining detected in these tumor types might, at least in part, be due to
      a TCF-3-dependent mechanism. Finally, we found that the presence of beta-catenin
      mutations significantly correlated with loss of nuclear immunoreactivity for an
      antibody raised against the N terminus of beta-catenin (alphaABC). Thus, a
      combined analysis with C terminus-beta-catenin antibodies and alphaABC Ab may
      represent a powerful investigative approach for the detection of beta-catenin
      structural alterations.

PMID- 14633603
TI  - Peritubular capillary loss after mouse acute nephrotoxicity correlates with down
      regulation of vascular endothelial growth factor-A and hypoxia-inducible factor-1
      alpha.
AB  - Although the response of kidneys acutely damaged by ischemia or toxins is
      dominated by epithelial destruction and regeneration, other studies have begun to
      define abnormalities in the cell biology of the renal microcirculation,
      especially with regard to peritubular capillaries. We explored the integrity of
      peritubular capillaries in relation to expression of vascular endothelial growth
      factor (VEGF)-A, hypoxia-inducible factor (HIF)-alpha proteins, and von Hippel
      Lindau protein (pVHL) in mouse folic acid nephropathy, a model in which acute
      tubular damage is followed by partial regeneration and progression to patchy
      chronic histological damage. Throughout a period of 14 days, in areas of cortical
      tubular atrophy and interstitial fibrosis, loss of VEGFR-2 and platelet
      endothelial cell adhesion molecule-expressing peritubular capillaries was
      preceded by marked decreases in VEGF-A transcript and protein levels.
      Nephrotoxicity was associated with tissue hypoxia, especially in regenerating
      tubules, as assessed by an established in situ method. Despite the hypoxia,
      levels of HIF-1 alpha, a protein known to up-regulate VEGF-A, were reduced.
      During the course of nephrotoxicity, levels of pVHL, a factor that destabilizes
      HIF-1 alpha, increased significantly. We speculate that that down-regulation of
      VEGF-A may be functionally-implicated in the progressive attrition of peritubular
      capillaries in areas of tubular atrophy and interstitial fibrosis; VEGF-A down
      regulation correlates with a loss of HIF-1 alpha expression which itself occurs
      in the face of increased tissue hypoxia.

PMID- 14633604
TI  - Gene expression profiling of alcoholic liver disease in the baboon (Papio
      hamadryas) and human liver.
AB  - The molecular pathogenesis of alcoholic liver disease (ALD) is not well
      understood. Gene expression profiling has the potential to identify new pathways
      and altered molecules in ALD. Gene expression profiles of ALD in a baboon model
      and humans were compared using DNA arrays. Reverse transcriptase-polymerase chain
      reaction and immunohistochemistry were used for downstream analysis of array
      results. cDNA array analysis revealed differential expression of several novel
      genes and pathways in addition to genes known to be involved in ALD pathogenesis.
      Overall gene expression profiles were similar in both species, with a majority of
      genes involved with fibrogenesis and xenobiotic metabolism, as well as
      inflammation, oxidant stress, and cell signaling. Genes associated with stellate
      cell activation (collagens, matrix metalloproteinases, tissue inhibitors of
      matrix metalloproteinase) were up-regulated in humans. Decreased expression of
      several metallothioneins was unexpected. Fourteen molecules related to the
      annexin family were up-regulated, including annexin A1 and A2. Immunofluorescence
      revealed a marked overexpression of annexin A2 in proliferating bile duct cells,
      hepatocyte cell surface, and selective co-localization with CD14-positive cells
      in human ALD. The gene expression profile of ALD is dominated by alcohol
      metabolism and inflammation and differs from other liver diseases. Annexins may
      play a role in the progression of fibrosis in ALD.

PMID- 14633605
TI  - Regulatory effects of iNOS on acute lung inflammatory responses in mice.
AB  - The role of endogenous NO in the regulation of acute lung injury is not well
      defined. We investigated the effects of inducible nitric oxide synthase (iNOS)
      and endothelial NOS (eNOS) on the acute inflammatory response in mouse lungs.
      Acute lung injury was induced by intratracheal instillation of bacterial
      lipopolysaccharide (LPS) into wild-type (WT) mice and mice deficient in iNOS
      (iNOS(-/-)) or eNOS (eNOS(-/-)). Endpoints of inflammatory injury were
      myeloperoxidase (MPO) content and leak of albumin into lung. Inflammatory injury
      was similar in WT and eNOS(-/-) mice but was substantially increased in iNOS(-/-)
      mice. Bronchoalveolar lavage (BAL) fluids of iNOS(-/-) and WT mice showed similar
      levels of CXC chemokines (MIP-2, KC) but enhanced levels of CC chemokines (MCP-1,
      MCP-3). Increased lung content of MPO in iNOS(-/-) mice was reduced by anti-MCP-1
      to values found in WT mice. In vitro stimulation of microvascular endothelial
      cells with LPS and IFN gamma revealed elevated production of CXC and CC
      chemokines in cells from iNOS(-/-) mice when compared to endothelial cells from
      iNOS(+/+) mice. Peritoneal macrophages from iNOS(-/-) donors also revealed
      increased production of CC chemokines after stimulation with LPS and interferon
      (IFN gamma). These data indicate that absence of iNOS causes enhanced lung
      inflammatory responses in mice which may be related to enhanced production of MCP
      1 by endothelial cells and macrophages. It appears that iNOS affects the lung
      inflammatory response by regulating chemokine production.

PMID- 14633606
TI  - Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice.
AB  - To address the role of neutrophil elastase in pulmonary emphysema, neutrophil
      elastase-deficient mice and wild-type littermate controls were exposed to long
      term cigarette smoke. Compared to wild-type littermates, mice that were deficient
      in neutrophil elastase were significantly protected (59%) from the development of
      emphysema. Previously, we demonstrated complete protection from emphysema in the
      absence of macrophage elastase. Further analysis revealed several interactions
      between these two elastases. Each elastase inactivated the endogenous inhibitor
      of the other, with neutrophil elastase degrading tissue inhibitor of
      metalloproteinase-1, and macrophage elastase degrading alpha-1-antitrypsin.
      Cigarette smoke-induced recruitment of both neutrophils and monocytes was
      impaired in the absence of neutrophil elastase. Moreover, there was less
      macrophage elastase activity secondary to decreased macrophage accumulation in
      neutrophil elastase-deficient mice. This study demonstrates a direct role for
      neutrophil elastase in emphysema and highlights the interdependence of the
      proteinases and inflammatory cells that mediate lung destruction in response to
      cigarette smoke.

PMID- 14633607
TI  - Nephrin promotes cell-cell adhesion through homophilic interactions.
AB  - Nephrin is a type-1 transmembrane protein and a key component of the podocyte
      slit diaphragm, the ultimate glomerular plasma filter. Genetic and acquired
      diseases affecting expression or function of nephrin lead to severe proteinuria
      and distortion or absence of the slit diaphragm. Here, we showed by using a
      surface plasmon resonance biosensor that soluble recombinant variants of nephrin,
      containing the extracellular part of the protein, interact with each other in a
      specific and concentration-dependent manner. This molecular interaction was
      increased by twofold in the presence of physiological Ca(2+)concentration,
      indicating that the binding is not dependent on, but rather promoted by Ca(2+).
      Furthermore, transfected HEK293 cells and an immortalized mouse podocyte cell
      line overexpressing full-length human nephrin formed cellular aggregates, with
      cell-cell contacts staining strongly for nephrin. The distance between plasma
      membranes at the nephrin-containing contact sites was shown by electron
      microscopy to be 40 to 50 nm, similar to the width of glomerular slit diaphragm.
      The cell contacts could be dissociated with antibodies reacting with the first
      two extracellular Ig-like domains of nephrin. Wild-type HEK293 cells were shown
      to express slit diaphragm components CD2AP, P-cadherin, FAT, and NEPH1. The
      results show that nephrin molecules exhibit homophilic interactions that could
      promote cellular contacts through direct nephrin-nephrin interactions, and that
      the other slit diaphragm components expressed could contribute to that
      interaction.

PMID- 14633608
TI  - Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that
      dendritic cells are early and sustained targets of infection.
AB  - Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that
      in many ways appears to be similar in humans and nonhuman primates; however,
      little is known about the development of EBOV hemorrhagic fever. In the present
      study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined
      sequentially over a 6-day period to investigate the pathological events of EBOV
      infection that lead to death. Importantly, dendritic cells in lymphoid tissues
      were identified as early and sustained targets of EBOV, implicating their
      important role in the immunosuppression characteristic of EBOV infections.
      Bystander lymphocyte apoptosis, previously described in end-stage tissues,
      occurred early in the disease-course in intravascular and extravascular
      locations. Of note, apoptosis and loss of NK cells was a prominent finding,
      suggesting the importance of innate immunity in determining the fate of the host.
      Analysis of peripheral blood mononuclear cell gene expression showed temporal
      increases in tumor necrosis factor-related apoptosis-inducing ligand and Fas
      transcripts, revealing a possible mechanism for the observed bystander apoptosis,
      while up-regulation of NAIP and cIAP2 mRNA suggest that EBOV has evolved
      additional mechanisms to resist host defenses by inducing protective transcripts
      in cells that it infects. The sequence of pathogenetic events identified in this
      study should provide new targets for rational prophylactic and chemotherapeutic
      interventions.

PMID- 14633609
TI  - Pathogenesis of Ebola hemorrhagic fever in primate models: evidence that
      hemorrhage is not a direct effect of virus-induced cytolysis of endothelial
      cells.
AB  - Ebola virus (EBOV) infection causes a severe and often fatal hemorrhagic disease
      in humans and nonhuman primates. Whether infection of endothelial cells is
      central to the pathogenesis of EBOV hemorrhagic fever (HF) remains unknown. To
      clarify the role of endothelial cells in EBOV HF, we examined tissues of 21 EBOV
      infected cynomolgus monkeys throughout time, and also evaluated EBOV infection of
      primary human umbilical vein endothelial cells and primary human lung-derived
      microvascular endothelial cells in vitro. Results showed that endothelial cells
      were not early cellular targets of EBOV in vivo, as viral replication was not
      consistently observed until day 5 after infection, a full day after the onset of
      disseminated intravascular coagulation. Moreover, the endothelium remained
      relatively intact even at terminal stages of disease. Although human umbilical
      vein endothelial cells and human lung-derived microvascular endothelial cells
      were highly permissive to EBOV replication, significant cytopathic effects were
      not observed. Analysis of host cell gene response at 24 to 144 hours after
      infection showed some evidence of endothelial cell activation, but changes were
      unremarkable considering the extent of viral replication. Together, these data
      suggest that coagulation abnormalities associated with EBOV HF are not the direct
      result of EBOV-induced cytolysis of endothelial cells, and are likely triggered
      by immune-mediated mechanisms.

PMID- 14633610
TI  - Gene expression patterns and gene copy number changes in dermatofibrosarcoma
      protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It
      is associated with the chromosomal translocation, t(17:22), which fuses the
      COL1A1 and PDGFbeta genes. We determined the characteristic gene expression
      profile of DFSP and characterized DNA copy number changes in DFSP by array-based
      comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed,
      paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA
      microarray analysis of global gene expression (nine cases). The nine DFSPs were
      readily distinguished from 27 other diverse soft tissue tumors based on their
      gene expression patterns. Genes characteristically expressed in the DFSPs
      included PDGF beta and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array
      CGH of DNA extracted either from frozen tumor samples or from paraffin blocks
      yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by
      COL1A1 and PDGF beta, respectively, were amplified in DFSP. Expression of genes
      in the amplified regions was significantly elevated. Our data shows that: 1) DFSP
      has a distinctive gene expression profile; 2) array CGH can be applied
      successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a
      characteristic amplification of sequences from chromosomes 17q and 22q,
      demarcated by the COL1A1 and PDGF beta genes, respectively, was associated with
      elevated expression of the amplified genes.

PMID- 14633611
TI  - Transgenic overexpression of granulocyte macrophage-colony stimulating factor in
      the lung prevents hyperoxic lung injury.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) plays an important role
      in pulmonary homeostasis, with effects on both alveolar macrophages and alveolar
      epithelial cells. We hypothesized that overexpression of GM-CSF in the lung would
      protect mice from hyperoxic lung injury by limiting alveolar epithelial cell
      injury. Wild-type C57BL/6 mice and mutant mice in which GM-CSF was overexpressed
      in the lung under control of the SP-C promoter (SP-C-GM mice) were placed in >95%
      oxygen. Within 6 days, 100% of the wild-type mice had died, while 70% of the SP-C
      GM mice remained alive after 10 days in hyperoxia. Histological assessment of the
      lungs at day 4 revealed less disruption of the alveolar wall in SP-C-GM mice
      compared to wild-type mice. The concentration of albumin in bronchoalveolar
      lavage fluid after 4 days in hyperoxia was significantly lower in SP-C-GM mice
      than in wild-type mice, indicating preservation of alveolar epithelial barrier
      properties in the SP-C-GM mice. Alveolar fluid clearance was preserved in SP-C-GM
      mice in hyperoxia, but decreased significantly in hyperoxia-exposed wild-type
      mice. Staining of lung tissue for caspase 3 demonstrated increased apoptosis in
      alveolar wall cells in wild-type mice in hyperoxia compared to mice in room air.
      In contrast, SP-C-GM mice exposed to hyperoxia demonstrated only modest increase
      in alveolar wall apoptosis compared to room air. Systemic treatment with GM-CSF
      (9 micro g/kg/day) during 4 days of hyperoxic exposure resulted in decreased
      apoptosis in the lungs compared to placebo. In studies using isolated murine type
      II alveolar epithelial cells, treatment with GM-CSF greatly reduced apoptosis in
      response to suspension culture. In conclusion, overexpression of GM-CSF enhances
      survival of mice in hyperoxia; this effect may be explained by preservation of
      alveolar epithelial barrier function and fluid clearance, at least in part
      because of reduction in hyperoxia-induced apoptosis of cells in the alveolar
      wall.

PMID- 14633612
TI  - Herpes simplex virus type 1 infection associated with atrial myxoma.
AB  - Some findings suggest an infectious factor in cardiac myxoma and certain
      histopathological features indicate herpes simplex virus type 1 (HSV-1)
      infection. We hypothesized that HSV-1 may be involved in the pathogenesis of
      cardiac myxoma. Paraffin-embedded tissue samples from 17 patients with atrial
      myxoma were investigated for HSV-1 antigen by immunohistochemistry and viral
      genomic DNA by nested polymerase chain reaction. The histogenesis and oncogenesis
      of atrial myxoma were assessed by the expression of calretinin, Ki67, and p53
      protein, respectively. Autopsy myocardial samples, including endocardium from 12
      patients who died by accident or other conditions, were used for comparison. HSV
      1 antigen was detected in atrial myxoma from 12 of 17 patients: 8 of these 12
      samples were positive also for HSV-1 DNA. No HSV-1 antigen or DNA was found in
      tissue from the comparison group. Antigens of HSV-2, varicella-zoster virus,
      Epstein-Barr virus, and cytomegalovirus were not found in atrial myxoma.
      Calretinin was found in myxoma cells of all 17 cases but Ki67 was present only in
      smooth muscle cells or infiltrating cells in some cases. p53 was not detectable
      in any myxoma. Most infiltrating cells were cytotoxic T lymphocytes. These data
      suggest that HSV-1 infection is associated with some cases of sporadic atrial
      myxoma and that these may result from a chronic inflammatory lesion of
      endocardium.

PMID- 14633613
TI  - Neutrophils sustain pathogenic CD8+ T cell responses in the heart.
AB  - This study explores the influence of innate immunity on CD8(+) T-cell responses
      against heart tissue. Adoptive transfer of ovalbumin-specific CD8(+) effector T
      cells into CMy-mOva mice, which express ovalbumin in cardiac myocytes, results in
      a lethal acute myocarditis. The inflammatory infiltrate in the heart includes
      neutrophils as well as T cells. We used anti-Ly6G antibody to transiently deplete
      neutrophils at the time of onset of disease. By day 7 after receiving 5 x 10(5)
      CD8(+) effector T cells, 100% of control Ig-treated CMy-mOva mice had died, while
      85% of anti-Ly6G-treated mice survived indefinitely. CD8(+) T-cell infiltration
      and tissue damage were present in both groups, but the disease was limited in the
      anti-Ly6G-treated mice, with a rapid disappearance of the adoptively transferred
      CD8(+) T cells within 11 days. Recovery occurred even though blood neutrophil
      counts began to rise 48 hours after the last anti-Ly6G treatment. Recovery was
      associated with a chronic CD4(+) cell infiltrate, and a rapid decline in
      expression of IFN-gamma and IP-10 mRNA in the myocardium. Neutrophil depletion
      did not effect survival of CMy-mOva mice that received 3 x 10(6) CD8(+) T cells.
      These data show that granulocytic inflammation sustains CD8(+) T-cell-mediated
      heart disease, which has important implications for the pathogenesis and
      treatment of acute myocarditis and allograft rejection.

PMID- 14633614
TI  - HoxD3 accelerates wound healing in diabetic mice.
AB  - Poorly healing diabetic wounds are characterized by diminished collagen
      production and impaired angiogenesis. HoxD3, a homeobox transcription factor that
      promotes angiogenesis and collagen synthesis, is up-regulated during normal wound
      repair whereas its expression is diminished in poorly healing wounds of the
      genetically diabetic (db/db) mouse. To determine whether restoring expression of
      HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene
      transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that
      is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in
      endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10
      days. More importantly, a single application of HoxD3 to db/db mice resulted in a
      statistically significant acceleration of wound closure compared to control
      treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement
      in diabetic wound repair was accompanied by increases in mRNA expression of the
      HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis
      and collagen deposition in the wounds. Although HoxD3-treated wounds also show
      improved re-epithelialization as compared to control db/db wounds, this effect
      was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we
      show that despite the dramatic increase in collagen synthesis and deposition in
      HoxD3-treated wounds, these wounds showed normal remodeling and we found no
      evidence of abnormal wound healing. These results indicate that HoxD3 may provide
      a means to directly improve collagen deposition, angiogenesis and closure in
      poorly healing diabetic wounds.

PMID- 14633615
TI  - Myofibroblast and endothelial cell proliferation during murine myocardial infarct
      repair.
AB  - Granulation tissue formation is a critical step in infarct repair, however, the
      kinetics of cell replication and the molecules that regulate this process are
      poorly understood. In uninjured mouse hearts and at 2 days post-infarction, very
      little DNA synthesis (measured by incorporation of a BrdU pulse) was detected in
      any cell type. Four days after permanent coronary occlusion, the rates of
      myofibroblast (smooth muscle alpha-actin and BrdU double-positive) and
      endothelial cell (CD31 and BrdU double-positive) proliferation were 15.4 +/- 1.1%
      and 2.9 +/- 0.5%, respectively. Most proliferating cells were located at the
      interface of the infarct and viable tissue. By 1 week, fibroblast and endothelial
      cell proliferation declined to 4.1 +/- 0.6% and 0.7 +/- 0.1%, respectively. In
      the 2-week infarct, the remaining necrosis had been phagocytosed, and fibroblast
      and endothelial cell proliferation were <0.5%. Although leukocytes were abundant
      throughout infarct repair, no significant proliferation was detected at any time
      in cells expressing CD45 or mac-3. Infarct size at 4 days was 38 +/- 5% of the
      left ventricle and contracted to 20 +/- 4% by 4 weeks. After 4 days, the chamber
      dilated to four times that of the control hearts and remained so for the duration
      of the time course. The vascular density (per mm(2)) declined from 3643 +/- 82 in
      control hearts to 2716 +/- 197 at 1 week and 1010 +/- 47 at 4 weeks post
      myocardial infarction (MI). The average percent area occupied by vessels did not
      change significantly between the groups but the area/vessel ( micro m(2))
      increased from 14.1 +/- 0.3 in control hearts to 16.9 +/- 1.9 at 1 week and 38.7
      +/- 7.9 at 4 weeks post-MI. These data indicate that mitogens for fibroblasts and
      endothelial cells peak within 4 days of infarction in the mouse heart. This
      provides the basis for identifying the responsible molecules and developing
      strategies to alter wound repair and improve cardiac function.

PMID- 14633616
TI  - Different types of ground glass hepatocytes in chronic hepatitis B virus
      infection contain specific pre-S mutants that may induce endoplasmic reticulum
      stress.
AB  - Ground glass hepatocyte (GGH) represents a histological hallmark of chronic
      hepatitis B virus infection and contains surface antigens in the endoplasmic
      reticulum (ER). Several types of GGHs are recognized at different hepatitis B
      virus replicative stages. The recent identification of pre-S mutants from GGHs
      encourages us to investigate whether different GGHs may harbor specific mutants
      and exhibit differential biological activities. In this study, we applied laser
      capture microdissection to isolate specific GGHs from a total of 50 samples on
      eight resected liver specimens. The surface genes in two major types of GGHs were
      analyzed. Type I GGHs expressed an inclusion-like pattern of hepatitis B surface
      antigens and harbored mutants with deletions over pre-S1 region, whereas type II
      GGHs, distributed in clusters and emerged at late replicative phase, contained
      mutants with deletions over pre-S2 region that defines a cytotoxic T lymphocyte
      (CTL) immune epitope, and may represent an immune escape mutant. Transfection of
      pre-S mutants in Huh7 revealed decreased syntheses of middle and small S proteins
      with accumulation of large surface antigen in ER, which in turn led to the
      activation of ER stress response with differential activities for different
      mutants. This study therefore demonstrates that different GGHs may contain
      specific mutants and exhibit differential biological activities.

PMID- 14633617
TI  - Amphiregulin overexpression results in rapidly growing keratinocytic tumors: an
      in vivo xenograft model of keratoacanthoma.
AB  - Keratoacanthoma (KA) is a variant of cutaneous squamous cell carcinoma (SCC)
      known for rapid growth and potential for involution. Little is known about the
      basis for the rapid growth because of the dearth of model systems. We
      hypothesized that amphiregulin (AR), a keratinocyte autocrine growth factor, had
      a significant role. Using immunohistochemistry, we compared 21 KA, 6 conventional
      SCC, and 6 basal cell carcinomas (BCC) for AR expression. All KA were positive
      for AR, the majority with strong immunoreactivity. The SCC were positive (5 of
      6), with generally weak staining; no BCC were positive. We developed laboratory
      model systems to study AR overexpression in keratinocytes and its role in the
      pathogenesis of KA. A retroviral transduction strategy was used to overexpress AR
      in the HaCaT keratinocyte-like cell line. The AR overexpressing cells (HaCaT-AR)
      displayed autonomous proliferation in serum-free media when compared with
      controls (HaCaT-NIE). To develop an in vivo model, xenografts of HaCaT-AR and
      HaCaT-NIE were grown on SCID mice. The HaCaT-NIE cells formed thin tumors
      resembling conventional SCC. The HaCaT-AR cells formed rapidly growing tumors
      with AR expression similar to KA. HaCaT-AR cells may represent a new system for
      the further evaluation of KA.

PMID- 14633618
TI  - Ontogenetic transition in fetal wound transforming growth factor-beta regulation
      correlates with collagen organization.
AB  - Fetal rat skin transitions from scarless fetal-type repair to adult-type repair
      with scar between day 16 (E16) and day 18 (E18) of gestation (term = 21.5 days).
      Deficient transforming growth factor (TGF)-beta 1 and -beta 2 injury response has
      been proposed as a mechanism for scarless fetal-type repair. However, previous
      fetal studies have inconsistently reported the degree of TGF-beta induction after
      injury. To minimize developmental variables in fetal versus adult TGF-beta
      regulation, we narrowed our study to wounded fetal animals. We hypothesize that
      TGF-beta ligand and receptor expression will be differentially regulated during
      the transition from early gestation (E16) wounds manifesting scarless fetal-type
      repair to late gestation (E19) wounds manifesting adult-type repair with scar. In
      this study, decreased and rapidly cleared TGF-beta 1 and -beta 2 expression
      accompanied by increased and prolonged TGF-beta 3 levels in wounded E16 animals
      correlated with organized collagen deposition. In contrast, increased and
      prolonged TGF-beta 1 and -beta 2 expression accompanied by decreased and delayed
      TGF-beta 3 expression in wounded E19 animals correlated with disorganized
      collagen architecture. Similarly, expression of TGF-beta receptors type I and II
      were also increased or prolonged in E19 animals. Our results implicate increased
      TGF-beta 1, -beta 2, and decreased TGF-beta 3 expression, as well as increased
      type I and II receptor expression in late gestation fetal scar formation.

PMID- 14633619
TI  - Identical allelic losses in mature teratoma and other histologic components of
      malignant mixed germ cell tumors of the testis.
AB  - Teratomas of the testis in post-pubertal patients are histologically diverse
      tumors that often coexist with other types of germ cell tumors. Using laser
      capture microdissection and loss of heterozygosity analysis, we investigated the
      clonality of mature teratoma and its relationship to other components of
      malignant mixed germ cell tumors to gain potential insight into the histogenetic
      relationship of teratoma with other germ cell tumor components. All 16 patients
      had mature teratoma as one component of their mixed germ cell tumors. The other
      histological subtypes included immature teratoma, seminoma, embryonal carcinoma,
      yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed
      on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was
      used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22
      32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21
      (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more
      components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed
      allelic loss in at least one of six microsatellite polymorphic markers analyzed.
      The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508,
      33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903,
      20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant
      allelic loss patterns between mature teratoma and all of the other germ cell
      tumor components were seen in 10 of 14 tumors in which mature teratoma showed
      loss of heterozygosity. Our data support the common clonal origin of mature
      teratoma with other components of malignant mixed germ cell tumors of the testis.

PMID- 14633620
TI  - Ischemia induces early expression of a new transcription factor (6A3-5) in kidney
      vascular smooth muscle cells: studies in rat and human renal pathology.
AB  - Acute renal failure, characterized by rapid decline in glomerular filtration
      rate, is a major cause of morbidity and mortality. During the evolution of renal
      diseases chronic ischemia develops. Indeed, acute or chronic renal failure may
      occur as a result of renal ischemia, which induces cells to dedifferentiate,
      proliferate, or become apoptotic. In this study, we have investigated the
      expression of a newly identified transcription factor, 6A3-5, under in vitro and
      in vivo conditions. Proliferating vascular smooth muscle were investigated in
      response to different mitogenic agents. The 6A3-5 expression was then studied in
      ischemic rat kidney, induced by renal pedicle clamping, followed, or not, by
      reperfusion. Subsequently human renal biopsies from early kidney grafts and
      chronic renal diseases were also investigated for 6A3-5 protein expression by
      immunohistochemistry. In vitro study shows an over-expression of 6A3-5 following
      2 to 4 hours stimulation by serum or Angiotensin II, of rat proliferating aortic
      smooth muscle cell. Moreover, in vivo study shows that this new protein is over
      expressed in rat kidney submitted to 45 minutes ischemia. An anti-6A3-5 antibody
      shows the protein to be expressed in smooth muscle cells of the arterioles and
      intermediate size arteries, in mesangial cells and interstitial myofibroblasts.
      In human biopsies of early kidney grafts and renal disease, the same up
      regulation of 6A3-5, as in acute ischemic situation, is observed. This 6A3-5
      expression is intimately associated with alpha-smooth muscle cell actin
      expression in mesangial cells, arteriolar smooth muscle cells as well as
      interstitial myofibroblasts. Transcription factor 6A3-5 could potentially be a
      novel early vascular marker of acute and chronic renal ischemic stress implicated
      in tissue remodeling.

PMID- 14633621
TI  - Id4 regulates mammary epithelial cell growth and differentiation and is
      overexpressed in rat mammary gland carcinomas.
AB  - Id4 belongs to a family of helix-loop-helix (HLH) proteins that impact cellular
      growth and differentiation via regulation of basic HLH transcription factors.
      Herein the rat Id4 gene was cloned (GenBank Accession No. AF468681). The
      expression of rat Id4 was examined in rat mammary gland tumors induced by 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in the human
      diet. By real-time polymerase chain reaction analysis, relative expression of Id4
      mRNA in carcinomas, adenomas, and normal tissue was 27, 6, and 1, respectively.
      Immunohistochemical analysis indicated statistically elevated nuclear expression
      for Id4 protein in carcinomas in comparison to adenomas and normal mammary gland.
      In carcinomas, Id4 nuclear expression was positively correlated with
      proliferation, invasiveness, and tumor weight (Fisher Exact Test or Spearman
      Correlation, P < 0.05). The consequence of enforced expression of Id4 on mammary
      epithelial cell proliferation, differentiation, and growth in soft agar was
      examined in HC11 cells, a well-characterized model for studying various aspects
      of mammary epithelial cell biology. After transient and stable transfection of
      HC11 cells, Id4 overexpression increased cell proliferation and inhibited
      lactogenic hormone-mediated differentiation as revealed by inhibition of beta
      casein promoter activity and beta-casein expression. In addition, enforced
      expression of Id4 in HC11 cells induced a statistically significant increase in
      colony growth in soft agar. The results implicate Id4 in rat mammary gland
      carcinogenesis and suggest that Id4 may contribute to carcinogenesis by
      inhibiting mammary epithelial cell differentiation and stimulating mammary
      epithelial cell growth.

PMID- 14633622
TI  - Expression profiling in ovarian clear cell carcinoma: identification of
      hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular
      target for therapy of ovarian clear cell carcinoma.
AB  - Of all of the epithelial ovarian cancers, clear cell carcinoma (CCC) of the ovary
      has the worst prognosis. We applied the oligonucleotide array technique to
      identify genes generally involved in CCC. Of the approximately 12,600 genes that
      were analyzed, 28 were expressed significantly differently between four CCC and
      seven non-CCC cell lines. Among 16 up-regulated genes in CCC, we further
      investigated a transcription factor, hepatocyte nuclear factor-1 beta (HNF-1
      beta). We validated up-regulation of HNF-1 beta in CCC in terms of both mRNA and
      protein level using real-time quantitative reverse transcriptase-polymerase chain
      reaction and immunoblotting. Immunohistochemical analysis of 83 surgically
      resected ovarian cancers showed that almost all CCC specimens (21 of 22 cases)
      had nuclear staining for HNF-1 beta, whereas most non-CCC specimens (60 of 61
      cases) showed no immunostaining or only focal and faint staining in the nucleus.
      Furthermore, we investigated the significance of HNF-1 beta expression in CCC
      using RNA interference. The reduction of HNF-1 beta expression by RNA
      interference induced apoptotic cell death in ovarian CCC cells, which was
      confirmed by terminal dUTP nick-end labeling and fluorescence-activated cell
      sorting analyses. Our results suggest that HNF-1 beta is not only an excellent
      CCC-specific molecular marker but also a molecular target for therapy of ovarian
      CCC.

PMID- 14633623
TI  - Androgenic regulation of oxidative stress in the rat prostate: involvement of
      NAD(P)H oxidases and antioxidant defense machinery during prostatic involution
      and regrowth.
AB  - Little is known about the roles of androgens in the regulation of redox state in
      the prostate, a cellular process believed to profoundly influence normal and
      aberrant prostate functions. We demonstrate that castration induced discrete
      oxidative stress (OS) in the acinar epithelium of rat ventral prostate (VP), as
      evident from marked increases in 8-hydroxy-2'-deoxy-guanosine and 4
      hydroxynonenal protein adducts in the regressing epithelium. Testosterone
      replacement partially reduced OS in VP epithelia of castrates, but the level
      remained higher than in intact rats. Quantification of steady-state mRNA levels
      of 14 genes involved in the anabolism and catabolism of reactive oxygen species
      (ROS) showed that castration resulted in dramatic increases of three ROS
      generating NAD(P)H oxidases (Noxs) including Nox1, gp91(phox), and Nox4,
      significant reductions of key ROS-detoxifying enzymes (superoxide dismutase 2,
      glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5), and unchanged levels
      of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and
      glutathione synthetase. Testosterone replacement in castrated rats partially
      reduced expression of Noxs but restored expression of superoxide dismutase 2,
      glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5 to complete normalcy
      and induced a compensatory increase in expression of catalase, glutathione
      reductase, gamma-glutamyl transpeptidase, and glutathione synthetase in the
      regenerating VP. Expression of superoxide dismutase 1, glutathione S-transferase
      pi, and glucose-6-phosphate dehydrogenase was unaffected by castration and
      testosterone replacement. These findings indicate androgen-deprivation induces OS
      in the rat VP through elevation of ROS anabolism and diminution of antioxidant
      detoxification. Androgen replacement partially reduces OS in rat VP to
      precastration levels. Expression of Noxs remained high amid a broad-based
      recovery of antioxidant defense mechanism(s). These data might have implications
      on the use of androgen blockade for prostate cancer prevention and androgen
      therapy for andropause treatment in elderly men.

PMID- 14633624
TI  - Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and
      lung fibrosis in mice.
AB  - Apoptosis of alveolar epithelial cells (AECs) has been implicated as a key event
      in the pathogenesis of lung fibrosis. Recent studies demonstrated a role for the
      synthesis and binding of angiotensin II to receptor AT1 in the induction of AEC
      apoptosis by bleomycin (BLEO) and other proapoptotic stimuli. On this basis we
      hypothesized that BLEO-induced apoptosis and lung fibrosis in mice would be
      inhibited by the AT1 antagonist losartan (LOS) or by targeted deletion of the AT1
      gene. Lung fibrosis was induced by intratracheal administration of BLEO (1 U/kg)
      to wild-type C57BL/6J mice. Co-administration of LOS abrogated BLEO-induced
      increases in total lung caspase 3 activity detected 6 hours after in vivo
      administration and reduced by 57% BLEO-induced caspase 3 activity in blood
      depleted lung explants exposed to BLEO ex vivo (both P < 0.05). Co-administration
      of LOS in vivo reduced DNA fragmentation and immunoreactive caspase 3 (active
      form) in AECs, measured at 14 days after intratracheal BLEO, by 66% and 74%,
      respectively (both P < 0.05). LOS also inhibited the accumulation of lung
      hydroxyproline by 45%. The same three measures of apoptosis and lung fibrosis
      were reduced by 89%, 85%, and 75%, respectively (all P < 0.01), in mice with a
      targeted disruption of the AT1a receptor gene (C57BL/6J-Agtr1a(tm1Unc)). These
      data indicate an essential role for angiotensin receptor AT1a in the pathogenesis
      of BLEO-induced lung fibrosis in mice and suggest that AT1 receptor signaling is
      required for BLEO-induced apoptosis of AECs in mice as it is in rat and human
      AECs.

PMID- 14633626
TI  - beta 1C Integrin expression in human endometrial proliferative diseases.
AB  - Integrins are ubiquitous cell adhesion molecules that are involved in maintaining
      normal tissue morphology and have been implicated in the aggressive behavior of
      several malignancies. beta 1C integrin is an alternatively spliced variant of the
      beta 1A integrin subunit that, at variance with beta 1A, inhibits epithelial cell
      proliferation. beta 1C integrin is expressed in non-proliferative, benign
      prostatic epithelium and is down-regulated in prostatic adenocarcinoma. In the
      current study, we examined beta 1C expression at mRNA and protein levels in 18
      endometrial adenocarcinoma and in 20 endometrial hyperplastic tissues, using
      Northern and Western blotting analysis and immunohistochemistry. The pattern of
      integrin expression was compared to that of the endometrium of 14 normal cycling
      women. The results of this study document inhibited beta 1C integrin expression
      in endometrial adenocarcinoma, both at the mRNA and protein levels, at variance
      with significantly up-regulated beta 1C mRNA expression in endometrial
      hyperplasia, in comparison with normal proliferative endometria. Our data suggest
      a key role of the regulation of beta 1C integrin expression in the pathogenesis
      of endometrial proliferative diseases: beta 1C integrin may act as growth
      modulator in cancer cells, playing a role in downstream intracellular signaling.

PMID- 14633625
TI  - Interleukin-1 alpha promotes tumor growth and cachexia in MCF-7 xenograft model
      of breast cancer.
AB  - Progression of breast cancer involves cross-talk between epithelial and stromal
      cells. This cross-talk is mediated by growth factors and cytokines secreted by
      both cancer and stromal cells. We previously reported expression of interleukin
      (IL)-1 alpha in a subset of breast cancers and demonstrated that IL-1 alpha is an
      autocrine and paracrine inducer of prometastatic genes in in vitro systems. To
      understand the role of IL-1 alpha in breast cancer progression in vivo, we
      studied the growth of MCF-7 breast cancer cells overexpressing a secreted form of
      IL-1 alpha (MCF-7IL-1 alpha) in nude mice. MCF-7IL-1 alpha cells formed rapidly
      growing estrogen-dependent tumors compared to parental cells. Interestingly, IL-1
      alpha expression alone was not sufficient for metastasis in vivo although in
      vitro studies showed induction of several prometastatic genes and matrix
      metalloproteinase activity in response to cross-talk between IL-1 alpha
      expressing cancer cells and fibroblasts. Animals implanted with MCF-7IL-1 alpha
      cells were cachetic, which correlated with increased leptin serum levels but not
      other known cachexia-inducing cytokines such as IL-6, tumor necrosis factor, or
      interferon gamma. Serum triglycerides, but not blood glucose were lower in
      animals with MCF-7IL-1 alpha cell-derived tumors compared to animals with control
      cell-derived tumors. Cachexia was associated with atrophy of epidermal and
      adnexal structures of skin; a similar phenotype is reported in triglyceride
      deficient mice and in ob/ob mice injected with leptin. Mouse leptin-specific
      transcripts could be detected only in MCF-7IL-1 alpha cell-derived tumors, which
      suggests that IL-1 alpha increases leptin expression in stromal cells recruited
      into the tumor microenvironment. Despite increased serum leptin levels, animals
      with MCF-7IL-1 alpha cell-derived tumors were not anorexic suggesting only
      peripheral action of tumor-derived leptin, which principally targets lipid
      metabolism. Taken together, these results suggest that cancer cell-derived
      cytokines, such as IL-1 alpha, induce cachexia by affecting leptin-dependent
      metabolic pathways.

PMID- 14633627
TI  - MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced
      protection against oxidant-induced lung injury.
AB  - The stress-inducible gene heme oxygenase (HO-1) has previously been shown to
      provide cytoprotection against oxidative stress. The mechanism(s) by which HO-1
      provides this cytoprotection is poorly understood. We demonstrate here that
      carbon monoxide (CO), a byproduct released during the degradation of heme by HO,
      plays a major role in mediating the cytoprotection against oxidant-induced lung
      injury. We show in vitro that CO protects cultured epithelial cells from
      hyperoxic damage. By using dominant negative mutants and mice deficient in the
      genes for the various MAP kinases, we demonstrate that the cytoprotective effects
      of CO are mediated by selective activation of the MKK3/p38 beta protein MAP
      kinase pathway. In vivo, our experiments demonstrate that CO at a low
      concentration protects the lungs, extends the survival of the animals, and exerts
      potent anti-inflammatory effects with reduced inflammatory cell influx into the
      lungs and marked attenuation in the expression of pro-inflammatory cytokines.

PMID- 14633628
TI  - Long-term exposure of proximal tubular epithelial cells to glucose induces
      transforming growth factor-beta 1 synthesis via an autocrine PDGF loop.
AB  - We have recently reported increased transforming growth factor (TGF)-beta1 gene
      transcription in proximal tubular cells within 12 hours of exposure to 25 mmol/L
      D-glucose, with a requirement for a second stimulus such as platelet-derived
      growth factor (PDGF) to increase its translation in short-term experiments. In
      the current study we investigated the effect on TGF-beta 1 production of
      prolonged exposure of proximal tubular cells to high glucose concentrations.
      Enzyme-linked immunosorbent assay of cell culture supernatant showed significant
      increase in latent TGF-beta 1 only after 7 days exposure to high glucose.
      Radiolabeling of glucose-stimulated cells with (3)H amino acids and subsequent
      immunoprecipitation of TGF-beta 1 demonstrated de novo synthesis from day 5 of
      high glucose exposure onwards. Similarly, polysome analysis showed enhanced
      translation of TGF-beta mRNA after 4 or more days of high glucose exposure. TGF
      beta 1 synthesis, following addition of glucose, was inhibited by blockade of the
      PDGF-alpha receptor subunit. Glucose did not alter PDGF expression, nor
      expression of PDGF alpha-receptors. Activation of the receptor following addition
      of 25 mm D-glucose could be demonstrated suggesting increased sensitivity to
      endogenous PDGF. Exposure to glucose activated p38MAP kinase, and inhibition of
      this activation abrogated both glucose induced TGF-beta 1 transcriptional
      activation and TGF-beta 1 synthesis. Inhibition of p38MAP kinase did not
      influence the effect of exogenous PDGF when cells were stimulated sequentially by
      glucose and PDGF. We postulate that glucose induces an early increase in TGF-beta
      1 transcription via activation of p38MAP kinase. In addition, glucose causes a
      late increase in PDGF-dependent TGF-beta 1 translation by enhancing cellular
      sensitivity to PDGF. This provides a potential explanation for the clinical
      observation that prolonged poor glycemic control may contribute to progression of
      diabetic nephropathy.

PMID- 14633629
TI  - Transfer of the active form of transforming growth factor-beta 1 gene to newborn
      rat lung induces changes consistent with bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia is a chronic lung disease of premature human infancy
      that shows pathological features comprising varying sized areas of interstitial
      fibrosis in association with distorted large alveolar spaces. We have previously
      shown that transfer of active transforming growth factor (TGF)-beta 1 (AdTGF beta
      1(223/225)) genes by adenovirus vector to embryonic lungs results in inhibition
      of branching morphogenesis and primitive peripheral lung development, whereas
      transfer to adult lungs results in progressive interstitial fibrosis. Herein we
      show that transfer of TGF-beta1 to newborn rat pups results in patchy areas of
      interstitial fibrosis developing throughout a period of 28 days after transfer.
      These areas of fibrosis appear alongside areas of enlarged alveolar spaces
      similar to the prealveoli seen at birth, suggesting that postnatal lung
      development and alveolarization has been inhibited. In rats treated with AdTGF
      beta 1(223/225), enlarged alveolar spaces were evident by day 21, and by 28 days,
      the mean alveolar cord length was nearly twice that in control vector or
      untreated rats. Hydroxyproline measurements confirmed the presence of fibrosis.
      These data suggest that overexpression of TGF-beta 1 during the critical period
      of postnatal rat lung alveolarization gives rise to pathological, biochemical,
      and morphological changes consistent with those seen in human bronchopulmonary
      dysplasia, thus inferring a pathogenic role for TGF-beta in this disorder.

PMID- 14633630
TI  - Humanized knock-in mice expressing chimeric prion protein showed varied
      susceptibility to different human prions.
AB  - Mice to which human prions efficiently transmit in short incubation periods are
      valuable not only as research tools of human prions but also as reliable
      diagnostic tools. We recently produced a line of knock-in mouse expressing a
      unique human-mouse chimeric PrP (Ki-ChM mouse), which has mouse-specific residues
      practically only at the C-terminal part after posttranslational modification, and
      here we attempted transmission of various human prions to assess the
      susceptibility profile of the mouse. Susceptibility varied considerably depending
      on prions inoculated: highly susceptible to MM1 and MV1 types of sporadic
      Creutzfeldt-Jakob disease (CJD), developing disease within approximately 150
      days, familial CJD with M232R mutation, and dura graft-associated CJD (dCJD)
      without amyloid plaque; less susceptible to MM2-type sporadic CJD and variant
      CJD, with some mice lacking any sign of transmission; and totally resistant to
      VV2 type sporadic CJD and dCJD with amyloid plaque. The rather short incubation
      time achieved by Ki-ChM mice suggests new approaches to produce mice that develop
      prion disease with very short incubation periods. We compared the characteristic
      susceptibility profile of Ki-ChM with those of other precedent transgenic mice
      and discussed, including the prospects in developing genetically engineered mice
      susceptible to human prions.

PMID- 14633631
TI  - Expression of a K48R mutant ubiquitin protects mouse testis from cryptorchid
      injury and aging.
AB  - Testis injury models can be useful for determining the in vivo function of genes.
      In this study, ubiquitin, a tag for 26S-proteasome degradation, was mutated at
      lysine 48 (K48R) to inhibit ubiquitin chain assembly. K48R transgenic mice had
      testes with delayed germ cell loss following the acute injury of experimental
      cryptorchidism, and were resistant to the chronic injury of aging-associated
      testicular atrophy. After 4 days of cryptorchid-mediated heat stress, the average
      weight of cryptorchid testes in wild-type ubiquitin mice was significantly lower
      (P < 0.05) than in K48R mutant ubiquitin mice, indicating that altered
      ubiquitination delayed germ cell death. Light microscopy confirmed that the
      testicular injury, in both wild-type and K48R ubiquitin mice, was due to germ
      cell death. In addition, wild-type ubiquitin mice aged 19 to 22 months showed
      greater testicular atrophy and decreased average seminiferous tubule diameter
      when compared with K48R-aged testes. These results demonstrate a resistance to
      testicular injury conferred by the K48R mutation, suggesting that ubiquitin
      mediated protein degradation is involved in the processing or modulation of
      testicular insults.

PMID- 14633632
TI  - Septic mice are susceptible to pulmonary aspergillosis.
AB  - Clinical data underscores the fact that subsequent high mortality rates occur in
      patients who survive acute septic episodes. Herein, we described a clinically
      relevant model of experimental sepsis that we believe will allow further
      investigation of the manner in which the pulmonary innate immune response is
      modulated after sepsis. C57BL/6 mice were subjected to cecal ligation and
      puncture (CLP) model, whereby the cecum was partially ligated and punctured nine
      times with a 21-gauge needle. This procedure was associated with 100% mortality
      at 3 days after surgery. In contrast, when mice subjected to CLP were treated
      with antibiotic beginning at 8 hours after surgery, and every 12 hours thereafter
      until 3 days, approximately 60% of the mice survived. Interestingly, CLP
      survivors quickly succumbed (100% mortality) to pulmonary infection when
      intratracheally challenged, at day 3 after CLP, with viable Aspergillus fumigatus
      conidia. No mortality was observed in conidia-challenged sham-operated mice. The
      defective innate immune response against A. fumigatus in CLP mice could not be
      explained by a failure of neutrophils to infiltrate the lungs. Instead, gene
      array analysis revealed that several components of the innate immune response,
      including the nuclear factor-kappaB signaling pathway, were down-regulated. Thus,
      we describe a system of sepsis-induced innate immune failure in the lungs of
      C57BL/6 mice.

PMID- 14633633
TI  - Phosphofructokinase muscle-specific isoform requires caveolin-3 expression for
      plasma membrane recruitment and caveolar targeting: implications for the
      pathogenesis of caveolin-related muscle diseases.
AB  - Previous co-immunoprecipitation studies have shown that endogenous PFK-M
      (phosphofructokinase, muscle-specific isoform) associates with caveolin (Cav)-3
      under certain metabolic conditions. However, it remains unknown whether Cav-3
      expression is required for the plasma membrane recruitment and caveolar targeting
      of PFK-M. Here, we demonstrate that recombinant expression of Cav-3 dramatically
      affects the subcellular localization of PFK-M, by targeting PFK-M to the plasma
      membrane, and by trans-locating PFK-M to caveolae-enriched membrane domains. In
      addition, we show that the membrane recruitment and caveolar targeting of PFK-M
      appears to be strictly dependent on the concentration of extracellular glucose.
      Interestingly, recombinant expression of PFK-M with three Cav-3 mutants [DeltaTFT
      (63 to 65), P104L, and R26Q], which harbor the same mutations as seen in the
      human patients with Cav-3-related muscle diseases, causes a substantial reduction
      in PFK-M expression levels, and impedes the membrane recruitment of PFK-M.
      Analysis of skeletal muscle tissue samples from Cav-3(-/-) mice directly
      demonstrates that Cav-3 expression regulates the phenotypic behavior of PFK-M.
      More specifically, in Cav-3-null mice, PFK-M is no longer targeted to the plasma
      membrane, and is excluded from caveolar membrane domains. As such, our current
      results may be important in understanding the pathogenesis of Cav-3-related
      muscle diseases, such as limb-girdle muscular dystrophy-1C, distal myopathy, and
      rippling muscle disease, that are caused by mutations within the human Cav-3
      gene.

PMID- 14633634
TI  - Chromosome 6 abnormalities correlated with thymoma progression.

PMID- 14633635
TI  - VEGF protein in human ischemic skeletal muscle.

PMID- 14633636
TI  - What's cooking? detection of important biomarkers in HOPE-fixed, paraffin
      embedded tissues eliminates the need for antigen retrieval.

PMID- 14633637
TI  - Unusual apoptosis in experimental cardiac rejection.

PMID- 14633638
TI  - Explaining decreased nitric oxide production in psoriatic lesions: arginase 1
      overexpression versus calcitonin gene-related peptide.

PMID- 14633639
TI  - Editorial changes in alcohol and alcoholism.

PMID- 14633640
TI  - Alcohol use in China.
AB  - AIMS: Over recent decades there has been a striking increase in alcohol
      consumption and related problems in China. As China holds over 22% of the world's
      population this has a significant potential impact on world health. Here we
      review English- and Chinese-language publications on the prevalence of alcohol
      consumption and related problems in China, and treatment and control measures to
      reduce these. METHODS: Medline search 1976-2002 and search of the China National
      Knowledge Infrastructure database 1996-2002. RESULTS: While alcohol is a
      traditional part of Chinese life, commercial alcohol production in China has
      increased more than 50-fold per capita since 1952. In parallel there is evidence
      of a marked increase in prevalence of alcohol dependence, which has moved from
      the ninth to the third most prevalent mental illness. The public health response
      to increase in alcohol-related disorders has commenced but is in need of further
      development. CONCLUSIONS: There is a need for increased policies and public
      health programmes to reduce alcohol related harm, and evaluation of outpatient
      treatment potential.

PMID- 14633641
TI  - Ethanol-reinforced behaviour predicts acquisition but not extinction of cocaine
      self-administration in the rat.
AB  - AIMS: The aim of the present study was to evaluate the relationship between
      operant oral ethanol self-administration and intravenous (i.v.) cocaine self
      administration in male Wistar rats. METHODS: Twenty-four rats were trained to
      lever press for 8% v/v ethanol in the sucrose-fading procedure. The subjects with
      the highest (high ethanol responders [HER], n = 7) and lowest (low ethanol
      responders [LER], n = 7) ethanol intakes were selected for further experiments.
      After a wash-out period, during which i.v. catheters were implanted, the HER and
      LER were trained to nose-poke for cocaine infusions (0.33 mg/kg/infusion, a FR1
      schedule) for nine daily sessions. RESULTS: The HER emitted more 'active' nose
      pokes and obtained more cocaine infusions during sessions 2-4. Drug-seeking
      behaviour in the absence of cocaine reinforcement was then assessed for three
      consecutive extinction sessions. No between-group differences were found in terms
      of extinction of cocaine seeking. Locomotor responses to a novel environment were
      also similar in both groups. CONCLUSIONS: The present results suggest that a
      propensity to self-administer ethanol predicts more rapid acquisition of cocaine
      self-administration behaviour but does not influence subsequent behaviour during
      extinction.

PMID- 14633642
TI  - Acute exposure of cultured neurones to ethanol results in reversible DNA single
      strand breaks; whereas chronic exposure causes loss of cell viability.
AB  - AIMS: Ethanol can create progressive neuropathological and functional alterations
      of neurones. However, the influence of exposure duration is still debated. It is
      difficult to specify the level of alcohol consumption leading to alcohol-induced
      brain damage. Moreover, the mechanism of toxicity is assumed to combine direct
      and metabolically induced effects, although numerous uncertainties remain.
      Finally, the genotoxic power of ethanol has not fully been investigated in the
      brain. In the experiment reported herein, primary cultures of neurones were
      exposed either chronically or acutely to doses of ethanol within the range of
      blood alcohol levels in intoxicated humans. The impact on the integrity of
      neurones was assessed by cytotoxicity tests and DNA alterations by single-cell
      gel electrophoresis (Comet assay) and flow cytometry. Chronic ethanol exposure,
      even at a low dose, was more harmful to neurones than acute exposure. Both
      significant reductions in cell viability and DNA alterations were observed in
      this condition. On the other hand, DNA repair capacities seemed to be preserved
      as long as the viability measured by specific tests was not affected. Instead,
      neurones entered a death cell process compatible with apoptosis.

PMID- 14633643
TI  - Correlates of externalizing symptoms in children from families of alcoholics and
      controls.
AB  - AIMS: This paper describes a new stage in the ongoing evaluation of the original
      families of sons of alcoholics and controls where we now focus on the
      relationships among relevant domains of functioning in their young sons and
      daughters. METHODS: The data were gathered from the 15-year follow-up of the
      families of the original probands (the fathers of these offspring) who had been
      selected from among students and non-academic staff at a university at
      approximately age 20. At the 15-year evaluation of these families, a structured
      interview and the Child Behavioral Checklist (CBCL) questionnaire were
      administered to a parent, usually the mother, of 145 offspring age seven through
      17. The eight domains evaluated here included the extended family histories of
      alcohol use disorders, parental alcoholism, independent mood or anxiety disorders
      in the grandparents and parents, the history of potential brain insults early in
      life, the absence of a biological parent in the home, and scores for
      internalizing symptoms, with externalizing symptoms as the dependent variable.
      RESULTS: Correlations among the domains were all in the predicted direction, a
      structural equation model revealed empirical results with an R(2) of 0.26, and
      there were high goodness of fit characteristics for hypothesized and empirical
      models. The results were similar for boys and girls and older versus younger
      offspring. CONCLUSIONS: An understanding of the relationships among
      characteristics in the offspring of the original probands offers the opportunity
      of establishing levels of functioning in relevant domains before the onset of
      alcohol-related problems or related disorders. The data presented here represent
      a baseline upon which future follow-ups will evaluate substance-related problems
      and disorders as this population matures.

PMID- 14633644
TI  - An alternative method for predicting attrition from an alcohol treatment
      programme.
AB  - AIMS: To test the predictive validity of a vignette methodology based on a Signal
      Detection model by examining treatment attrition within an alcohol clinic.
      METHODS: Participants were asked to categorize vignettes that described
      individuals drinking alcohol as problem or nonproblem alcohol use at the
      beginning of a 4-week intensive course of treatment. These participants were
      divided retrospectively into two groups: those who completed treatment and those
      who dropped-out of treatment. A matched post-treatment long-term abstainer group
      was also tested. RESULTS: Signal Detection analyses demonstrated that response
      bias scores predicted who would drop out of treatment (P = 0.01). CONCLUSIONS:
      The vignette methodology provided useful levels of prediction in an applied
      clinical setting. It was argued that verbal reports from problem alcohol users
      may be more usefully conceptualized in terms of sensitivity and response bias
      than in terms of memory or 'truth'.

PMID- 14633645
TI  - Combining carbohydrate-deficient transferrin and gamma-glutamyltransferase to
      increase diagnostic accuracy for problem drinking.
AB  - AIM: To examine methods for combining quantitative results for serum carbohydrate
      deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and/or aspartate
      aminotransferase (AST), and refining these by inclusion of patient
      characteristics. METHODS: Data from 1684 subjects, recruited from the general
      population, abstainer groups and alcohol treatment centres (participants in the
      five nations WHO/ISBRA study of biological markers of alcohol use), were used to
      develop clinical rules for combining results of GGT, AST and CDT. The algorithm
      derived by Sillanaukee and Olsson was tested, and compared with new algorithms
      derived by logistic regression and discriminant analysis. Diagnostic accuracy was
      assessed by area underneath the receiver operator characteristic curve. Effects
      of adding gender and clinical information to the algorithm were estimated.
      RESULTS: The predictive ability of combination rules derived from the two studies
      and by two different statistical techniques was remarkably consistent. For men,
      combining lnCDT and lnGGT provided the best accuracy for detecting daily
      consumption of 60 g ethanol or more in the past 30 days. For women, GGT alone
      provided the best accuracy for that consumption level. Clinical variables added
      significantly to the diagnostic accuracy of the models for both men and women,
      and conversely the test results modified the probability of problem drinking as
      assessed from clinical data alone. A graphic method was produced to help
      clinicians estimate probabilities for consumption of 60 g or more per day.
      CONCLUSIONS: Combining biochemical markers enhances detection of problem drinking
      in men but not in women. Information on clinical variables increases the ability
      to correctly detect problem drinking.

PMID- 14633646
TI  - Influence of different types of alcoholic beverages on self-reported health
      status.
AB  - AIMS: This study investigated the effect of the consumption of wine, beer and
      spirits on self-reported health status. METHODS: A sample of 14950 individuals
      was randomly selected from the total population register in Sweden in 1996-97.
      Their self-reported health status and consumption of wine, beer and spirits were
      assessed at face-to-face interviews. RESULTS: Of 11606 individuals in the age
      range 16-84 years, 2659 reported a poor health status. Consumption of wine was
      associated with a decreased odds ratio (OR) (0.56; 95% confidence interval (CI)
      0.50-0.63) for poor, self-reported health status, as compared with non-users.
      Consumers of fortified wine, beer, strong beer and hard liquor had a similar,
      self-reported health status to that of non-consumers. The results were adjusted
      for age, sex and total alcohol consumption. Adjustments for body-mass index,
      smoking, educational level and physical activity did not change the results. The
      relationship between poor self-reported health status and intake of wine had a
      form similar to a 'U' with the lowest OR among individuals consuming small to
      moderate amounts of wine. CONCLUSIONS: The study shows that a moderate
      consumption of wine was associated with a positive effect on the self-reported
      health status. Factors related to lifestyle may be underlying causes.

PMID- 14633647
TI  - Oestradiol and human male alcohol-related aggression.
AB  - AIMS: In comparison to androgens, almost nothing is known about the role of
      endogenous oestrogens in human aggressive behaviour. This new aspect was studied
      in the present investigation involving men with a history of alcohol-related
      aggression (AGG+) and in an age-matched male control population (AGG-). METHODS:
      Male AGG+ volunteers were recruited through advertisements and the controls were
      drawn from the Finnish Population Register. Alcohol misuse and interpersonal
      partner violence were estimated by questionnaires. Endogenous hormone levels were
      measured from morning plasma samples. RESULTS: A positive association emerged
      between plasma oestradiol and emotional negotiation during interpersonal conflict
      situations. Furthermore, a negative association was observed between oestradiol
      and testosterone-related physical, violent, aggression in the AGG+ men. In
      addition, oestradiol, rather than testosterone, was positively associated with
      psychological aggression in both groups of men. CONCLUSION: It is suggested that
      endogenous female sex hormones may be related to empathic behaviour and could,
      thus, represent a counter-balancing factor in alcohol-related male aggressive
      behaviour. Altogether, oestrogen may represent a multifactor ingredient in the
      complex interactions of partner conflicts.

PMID- 14633648
TI  - Attitudes and management of alcohol problems in general practice: descriptive
      analysis based on findings of a World Health Organization international
      collaborative survey.
AB  - AIMS: To determine if general practitioners' (GPs) experience of education on
      alcohol, support in their working environment for intervening with alcohol
      problems, and their attitudes have an impact on the number of patients they
      manage with alcohol problems. METHODS: 1300 GPs from nine countries were surveyed
      with a postal questionnaire as part of a World Health Organization (WHO)
      collaborative study. RESULTS: GPs who received more education on alcohol (OR =
      1.5; 95% CI, 1.3-1.7), who perceived that they were working in a supportive
      environment (OR = 1.6; 95% CI, 1.4-1.9), who expressed higher role security in
      working with alcohol problems (OR = 2.0; 95% CI, 1.5-2.5) and who reported
      greater therapeutic commitment to working with alcohol problems (OR = 1.4; 95%
      CI, 1.1-1.7) were more likely to manage patients with alcohol-related harm.
      CONCLUSION: Both education and support in the working environment need to be
      provided to enhance the involvement of GPs in the management of alcohol problems.

PMID- 14633649
TI  - Alcoholism: low standing with the public? Attitudes towards spending financial
      resources on medical care and research on alcoholism.
AB  - AIMS: To assess the extent to which the German public supports the allocation of
      financial resources to the care of people with alcoholism and to research on
      alcoholism as compared with other conditions. METHODS: 5025 interviews were
      conducted in the scope of a representative survey in Germany during May and June
      of 2001, using a personal, fully structured interview. RESULTS: Respondents most
      frequently selected alcoholism as the disease for which medical care expenditures
      could be spared and cut down and on which research funds should neither be spent
      in the first place nor should be spent at all. CONCLUSION: Our study shows that
      despite the spread of the concept 'alcoholism is an illness', this disease is
      still treated 'unfavourably' compared to other conditions. Health campaigns that
      increase the public's awareness that alcoholism is not a personal failure but an
      illness with severe medical and social consequences may help reduce the public
      acceptance of structural discrimination.

PMID- 14633650
TI  - Strength of the relationship between tobacco smoking, nicotine dependence and the
      severity of alcohol dependence syndrome criteria in a population-based sample.
AB  - AIMS: Little is known about the relationship between current and past smoking
      behaviour and the severity of alcohol dependence. The purpose was to explore the
      strength of this relationship. METHODS: A random population sample of 18 to 64
      year-olds from northern Germany was used (n = 4075; participation rate: 70%). It
      included 761 cigarette smokers fulfilling at least one alcohol-dependence
      criterion. The severity of alcohol dependence according to the alcohol-dependence
      syndrome criteria frequency (ASF) was estimated by a standardized questionnaire
      based on diagnostic instruments of the alcohol dependence syndrome and which
      included five response categories, from 'never' to 'daily'. Nicotine dependence
      was diagnosed according to the Diagnostic and Statistical Manual of mental
      disorders (DSM-IV) with the Composite International Diagnostic Interview (CIDI).
      As a second measure, the Fagerstrom Test of Nicotine Dependence (FTND) was used.
      RESULTS: The number of cigarettes and years of daily smoking, nicotine
      dependence, and the number of nicotine dependence symptoms each showed a
      relationship with the ASF. Effect size (w) were 0.17-0.21 for chi-squared
      (chi(2)) tests. In a general linear regression model with the ASF as the
      dependent variable (R(2) = 0.17), number of years of daily smoking, age at onset
      of smoking, number of attempts to reduce or quit, the number of nicotine
      dependence symptoms according to DSM-IV and the FTND sum score were retained as
      independent variables. CONCLUSIONS: Long-term smoking, a large number of nicotine
      dependence symptoms according to DSM and a strong urge to smoke according to the
      FTND are related with a high ASF.

PMID- 14633651
TI  - Dependence on legal psychotropic drugs among alcoholics.
AB  - AIMS: Dependence on legal psychotropic drugs (PTD) has been reported to have
      increased in alcoholics, but previous studies report conflicting results
      concerning the rate of increase and clinical characteristics. The aim of the
      present study was first, to assess the dependence rate of PTD among alcoholics in
      open and institutionalized care, and to compare these populations with the
      general population, and second, to assess rates and doses of high- and low-dose
      PTD-dependence among alcoholics. METHODS: In 1997, alcoholics in open and
      institutionalized care were asked to anonymously fill in a questionnaire on their
      drug use and dependence. Healthy controls were included. The number of attending
      subjects was 130 open-care alcoholics at the Department of Alcohol and Drug
      Diseases in Malmo, Sweden; 23 alcoholics in institutionalized care at Karlsvik
      Rehabilitation Centre in Hoor, Sweden; and 120 healthy controls at Vardcentralen
      Kirseberg, a primary health care centre located in a Malmo area. The approximate
      attendance rate was 75, 70 and 95%, respectively. The questionnaire was based on
      DSM-IV criteria for dependence. RESULTS: The total rate of PTD-dependent
      alcoholics was higher in the institutionalized group (35%) than in the open-care
      setting (14%): difference in proportions (p(1)-p(2) 21%; 95% CI: 1%, 41%).
      Alcoholics were more often PTD-dependent (17%) than were healthy controls (2%),
      (p(1)-p(2) 15%; 95% CI: 9%, 21%). Benzodiazepines (BZD) were the most common PTD.
      Only four out of a total of 23 BZD-dependent alcoholics developed high-dose BZD
      dependence. Those subjects were also misusing other drugs, including cannabis.
      CONCLUSIONS: We conclude that alcoholism is associated with legal PTD-dependence
      and illegal drug misuse. High-dose BZD-dependence is infrequent among BZD
      dependent alcoholics.

PMID- 14633652
TI  - Sertraline for the prevention of relapse in detoxicated alcohol dependent
      patients with a comorbid depressive disorder: a randomized controlled trial.
AB  - AIMS: We performed a double-blind, placebo-controlled randomized trial of
      sertraline in recently detoxified alcohol-dependent patients with current
      depressive symptoms. The objectives of the study were to evaluate the efficacy of
      sertraline at achieving stable abstinence, at ameliorating depressive symptoms
      and at improving quality of life in these patients. METHODS: The study included
      83 patients, who received either sertraline (50-150 mg/day) or placebo for 24
      weeks. The primary outcome criteria were the rate of relapse into alcohol
      consumption and the rate of response on the Montgomery and Asberg Depression
      Rating Scale (MADRS). RESULTS: At the end of the treatment period, relapse rates
      were 23.1% in the placebo group and 31.8% in the sertraline group. Responder
      rates for depression were 38.5% for the placebo group and 44.2% for the
      sertraline group. There was no significant difference between treatment groups
      with either variable. However, when patients were stratified into severe (MADRS
      score >or=26) and moderate (MADRS score <26) depression at inclusion, a
      significant treatment benefit with sertraline was observed in the former group.
      Quality of life, determined by the SF-36, improved in both groups, with more
      benefit observed for the sertraline group on mental health items. Sertraline was
      well tolerated, and the incidence of adverse events was similar in the two
      treatment groups. CONCLUSIONS: The explanation for the overall good outcome in
      both treatment groups and for the inability to demonstrate a clear treatment
      effect may reside in the clinical features of the patients included.

PMID- 14633653
TI  - Acceptability of various brief intervention approaches for hazardous drinking
      among university students.
AB  - AIMS: To determine the acceptability to university students of practitioner
      delivered screening and brief intervention (SBI) versus a novel approach-web
      based SBI (e-SBI). METHODS: A random sample of 1910 university students was
      invited to indicate their preferences for various brief intervention approaches
      in an internet survey. RESULTS: e-SBI was the most popular intervention. It was
      favoured by 81% of all students and 82% of hazardous drinkers. CONCLUSIONS: e-SBI
      is a promising approach for the reduction of hazardous drinking among young
      people.

PMID- 14633654
TI  - Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal
      carcinoma cancer cells.
AB  - Cox-1 and Cox-2 specific inhibitors exert chemo-preventative activity. However,
      the exact mechanisms for this activity remain unclear. Increasing evidence
      suggests that non-steroidal anti-inflammatory drugs regulate gene expression,
      which may be responsible, in part, for this activity. In this study, human
      colorectal carcinoma HCT-116 cells were treated with the Cox-1 specific inhibitor
      SC-560 and the Cox-2 specific inhibitor SC-58125 to evaluate their ability to
      induce apoptosis, inhibit cell proliferation, inhibit growth on soft agar and
      modulate gene expression. The Cox-1 specific inhibitor, SC-560 significantly
      induced apoptosis and inhibited the growth of HCT-116 cells on soft agar, an in
      vitro assay for tumorigenicity. SC-58125 moderately induced apoptosis and
      inhibited growth on soft agar at higher concentrations than were required for SC
      560. Previously, we reported that the potent chemo-preventative drug sulindac
      sulfide altered the expression of eight genes including several transcription
      factors that may be linked to this drug's chemo-preventative activity. HCT-116
      cells were treated with various concentrations of SC-560 or SC-58125 and changes
      in the expression of these eight genes were determined by real-time reverse
      transcription- polymerase chain reaction. SC-560 modulated mRNA expression of the
      eight genes studied. In contrast, SC-58125 required approximately 5-10-fold
      higher concentrations to achieve similar degrees of gene modulation in six of
      eight genes. Changes in protein expression by SC-560 also occurred for five of
      these genes with antibodies available (NAG-1, ATF3, C/EBPbeta, MAD2 and MSX1). In
      conclusion, this is the first report to suggest that like sulindac sulfide, the
      Cox-1 specific inhibitor SC-560 appears to elicit chemo-preventative activity by
      altering gene expression, while the chemo-preventative effects of SC-58125 are
      complex and probably work through these and other mechanisms, such as the
      inhibition of Cox-2.

PMID- 14633655
TI  - Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea
      induced mammary carcinogenesis in rats.
AB  - Studies in our laboratory on the role of P-glycoprotein (Pgp, coded by mdr1 gene)
      have led to the hypothesis that over-expression of Pgp is closely associated with
      the development of cancer. It was conceived therefore that inhibitors of Pgp
      should inhibit the development of cancer. We have reported that PSC833 (PSC), a
      potent inhibitor of Pgp, inhibits the development of liver cancer in rats.
      Similarly, based on the intrinsic over-expression of Pgp in experimental mammary
      carcinogenesis, we studied the effect of PSC on N-methyl-N-nitrosourea induced
      mammary cancer in female Sprague-Dawley rats. The study indicates that PSC at
      daily dietary doses of 15 (PSC15) and 30 mg/kg (PSC30) body wt resulted in dose
      dependent inhibition of the incidence as well as the growth of mammary tumors.
      Compared with controls, PSC15 and PSC30 inhibited: (i) mean tumor multiplicity by
      32 and 67%, (ii) median tumor burden by 46 and 93% and (iii) incidence of
      ulcerated tumors by 40 and 82%, respectively. Most remarkably, PSC delayed median
      tumor incidence by 8 weeks, and exerted a 100% inhibitory effect on the incidence
      of large tumors, 4 cm(3) and greater. In all the cases, although the inhibitory
      effect of PSC was evident at both doses, only PSC30 exhibited statistical
      significance. A possible compounding effect that was also observed in PSC30
      treated rats was a decrease in body weight gain not attributed to diminished food
      consumption. All in all, consistent with recent reports, which have demonstrated
      inhibition of cancer development by compromising Pgp function, this study
      introduces a novel role for Pgp in breast cancer and potentially an unexplored
      therapeutic approach in treating the disease.

PMID- 14633656
TI  - Overexpression of cyclin E protein is associated with specific mutation types in
      the p53 gene and poor survival in human breast cancer.
AB  - Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle.
      Overexpression of cyclin E has been observed in several malignancies and is
      associated with high proliferation, aberrant expression of other cell cycle
      regulators and chromosomal instability in vitro. To explore potential
      associations between cyclin E deregulation and inactivation of the p53 tumor
      suppressor gene in human breast cancer, we investigated the immunohistochemical
      expression of cyclin E in paraffin embedded breast cancers from 270 women with
      known p53 status by cDNA based sequencing of the p53 gene. The breast cancers
      were divided into three subgroups according to the percentage of cyclin E
      positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72
      (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of
      the breast cancers with high cyclin E had p53 gene mutations, compared with 14%
      (24/171) of those with low cyclin E content (P < 0.0001). In p53 mutated breast
      cancers high cyclin E content was associated with insertions, deletions and
      nonsense point mutations in the p53 tumor suppressor gene, whereas low cyclin E
      was linked to p53 missense point mutations. We also observed statistically
      significant associations between a high cyclin E content and aneuploidy, high S
      phase, larger tumor size, estrogen receptor negativity, presence of axillary node
      metastases and high tumor grade. High cyclin E content was associated with poor
      overall survival in univariate and multivariate analysis (hazard ratio 2.4, 95%
      confidence interval 1.3-4.5). In summary, our findings demonstrate that
      overexpression of cyclin E is associated with an aggressive tumor phenotype and
      specific types of p53 mutations.

PMID- 14633657
TI  - Nitric oxide induces expression of cyclooxygenase-2 in mouse skin through
      activation of NF-kappaB.
AB  - Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are
      frequently overexpressed in tumor tissues or transformed cells. In the present
      work, we assessed the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on
      expression of iNOS and COX-2 in mouse skin. Topical application to the dorsal
      skin of female ICR mice of 10 nmol TPA led to maximal induction of iNOS and COX-2
      protein expression at approximately 2 and 4 h, respectively. When applied
      topically onto shaven backs of mice 30 min prior to TPA, the NOS inhibitor
      aminoguanidine (AG) inhibited the expression of COX-2 protein at the
      pharmacologically effective dose. Pretreatment with a more specific iNOS
      inhibitor, N(G)-nitro-l-arginine-methyl ester, also suppressed TPA-induced COX-2
      expression. Immunohistochemical analysis of TPA-treated mouse skin using an anti
      nitrotyrosine antibody reveals enhanced levels of nitrotyrosine protein localized
      in epidermal and dermal layers. Topical application of NO donors, such as sodium
      nitroprusside (SNP) and S-nitroso-N-acetyl-d,l-penicillamine, induced expression
      of COX-2 in mouse skin, which was attenuated by the NO scavenger 2-(4
      carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide. SNP treatment
      stimulated NF-kappaB activation in mouse skin, which was associated with the
      degradation of IkappaBalpha. Topical application of inhibitors of NF-kappaB, such
      as pyrrolidine dithiocarbamate or N-alpha-p-tosyl-l-lysine chloromethylketone,
      inhibited the SNP-induced COX-2 expression. SNP induced a weak but concentration
      related increase in COX-2 expression in cultured mouse keratinocytes, which was
      abolished by treatment with SN50, a specific inhibitor of nuclear translocation
      of NF-kappaB. Mouse keratinocytes treated with SNP exhibited an elevated NF
      kappaB-driven COX-2 promoter activity. Topical application of AG (10 micro mol)
      prior to each TPA treatment after initiation reduced the multiplicity of
      papillomas by 44% at 22 weeks. In conclusion, up-regulation of COX-2 by NO may be
      mediated by activation of NF-kappaB in mouse skin, which provides a molecular
      mechanism by which COX-2 is induced during tumor promotion.

PMID- 14633658
TI  - Exposure of mouse skin to organic peroxides: subchronic effects related to
      carcinogenic potential.
AB  - Screening of newly synthesized organic peroxides for tumor initiating/promoting
      activity would be greatly facilitated if predictive methodologies could be
      developed using topical exposures shorter than those required for definitive
      tumor assessment in mouse skin models. Nine organic peroxides [benzoyl peroxide
      (BZP), di-t-butyl peroxide (DTBP), t-butyl peroxybenzoate (TBPB), p-t-butyl
      isopropylbenzene hydroperoxide (TBIBHP), cumene hydroperoxide (CHP), dicetyl
      peroxydicarbonate (DPD), dicumyl peroxide (DCP), methyl ethyl ketone peroxide
      (MEKP) and O,O-t-butyl-O-(2-ethylhexyl) monoperoxycarbonate (TBEC)] were
      evaluated for their ability to increase biomarkers of tumor promotion in mouse
      skin, i.e. sustained epidermal hyperplasia, dermal inflammation and oxidative DNA
      damage. Evaluations were performed using SENCAR mice exposed topically for 4
      weeks. The organic peroxides varied in their effects on these biomarkers. BZP,
      TBPB and TBIBHP exhibited significant increases in all three biomarkers
      associated with tumor promoting activity, CHP produced increases only in
      sustained epidermal hyperplasia and dermal inflammation, MEKP and DCP produced
      increases only in sustained epidermal hyperplasia and TBEC produced an increase
      only in dermal inflammation. DTBP and DPD had no effect on the three parameters
      studied. TBPB and TBIBHP were selected for further examination of their ability
      to produce mutations in codons 12, 13 and 61 of the c-Ha-ras protooncogene, i.e.
      those mutations known to be involved in the initiation of mouse skin tumors,
      because they were the only peroxides to exhibit significant positive results in
      all assays except the Ha-ras mutation following 4 weeks of exposure. Evaluations
      were performed using SENCAR mice dosed topically for 8 or 12 weeks in a complete
      carcinogenesis protocol or 16 weeks in an initiation/promotion protocol using
      7,12-dimethylbenz[a]anthracene, urethane, benzo[a]pyrene and N-methyl-N'-nitro-N
      nitrosoguanidine as positive controls. Neither TBPB nor TBIBHP produced
      detectable mutations in the c-Ha-ras protooncogene, indicating that they are not
      likely to possess tumor initiating or complete carcinogenic activity.

PMID- 14633659
TI  - Selective expression of glutathione S-transferase genes in the murine
      gastrointestinal tract in response to dietary organosulfur compounds.
AB  - A short-term feeding regimen was designed to analyze the effects of compounds
      such as diallyl disulfide (DADS), diallylthiosulfinate (allicin) from garlic and
      butylated hydroxyanisole (BHA) on glutathione S-transferase (GST) expression in
      the gastrointestinal tract and liver of male mice. After animals were force-fed
      these compounds, tissue GSTs were purified and individual subunits resolved by
      HPLC and identified on the basis of mass spectrometry (ESI MS) and
      immunoreactivity data. The effects of DADS and allicin on GST expression were
      especially prominent in stomach and small intestine, where there were major
      coordinate changes in GST subunit profiles. In particular, the transcripts of the
      mGSTM1 and mGSTM4 genes, which share large segments of common 5'-flanking
      sequences, and their corresponding subunits were selectively induced. Levels of
      alpha class subunits also increased, whereas mGSTM3 and mGSTP1 were not affected.
      The inducible mGSTA5 and non-responsive mGSTM3 subunits had not been identified
      previously. Liver and colon GSTs were also affected to a lesser extent, but this
      short-term feeding regimen had no effect on GST subunit patterns from other
      organs, including heart, brain and testis. Real-time PCR (TaqMan) methods were
      used for quantitative estimations of relative amounts of the mRNAs encoding the
      GSTs. Effects on the transcripts generally paralleled changes at the protein
      level, for the most part, however, the greatest relative increases were observed
      for those mRNAs that were expressed at low abundance constituitively. Mechanisms
      by which the organosulfur compounds operate to affect GST transcription could
      involve reversible modification of certain protein sulfhydryl groups, shifts in
      reduced glutathione/oxidized glutathione ratios and resultant changes in cellular
      redox status.

PMID- 14633660
TI  - Expression of PEA3/E1AF/ETV4, an Ets-related transcription factor, in breast
      tumors: positive links to MMP2, NRG1 and CGB expression.
AB  - The PEA3/E1AF/ETV4 gene encodes an Ets-related transcription factor that is
      expressed in the epithelial cells of the mammary gland. Previous reports have
      shown that PEA3 can up-regulate promoter activities of many genes associated with
      tumorigenesis. A significant fraction of those encode matrix metalloproteinases
      (MMP genes) required for degradation of the extracellular matrix. To better
      obtain a molecular characterization of PEA3 expression in sporadic breast cancer,
      we quantified PEA3 mRNA by means of real-time reverse transcriptase-polymerase
      chain reaction assay in a large series of human primary breast tumors. PEA3
      expression showed wide variations in tumor tissues, being under-expressed in 30
      of 130 (23.1%) and over-expressed in 18 of 130 (13.8%) compared with normal
      breast tissues. High PEA3 mRNA levels correlated significantly with Scarff-Bloom
      Richardson histopathological grade III (P = 0.018) but not with poor prognosis,
      suggesting that PEA3 is a marker of tumor aggressiveness rather than a prognostic
      factor in human breast cancer. We also observed positive links between the
      expression of PEA3 and those of MKI67 and ERBB2 (P = 0.034 and P = 0.045,
      respectively) and an inverse relationship with ERalpha (P = 0.0016). Our results
      do not support recent findings suggesting that PEA3 could be a tumor-suppressor
      gene that can act therapeutically in ERBB2 over-expressed tumors. Our results
      also suggest major roles of the MMP2, NRG1 and CGB genes (which encode type I
      gelatinase, heregulin and human chorionic gonadotropin beta subunit,
      respectively) in the PEA3 pathway dysregulation observed in breast cancer. Taken
      together, the data confirm the role of the PEA3 gene in breast tumorigenesis, and
      suggest the existence of numerous other still unknown genes transactivated by the
      PEA3 transcription factor.

PMID- 14633661
TI  - Complex effects of Ras proto-oncogenes in tumorigenesis.
AB  - Ras proteins have been found mutated in about one-third of human tumors. In
      vitro, Ras has been shown to regulate distinct and contradictory effects, such as
      cellular proliferation and apoptosis. Nonetheless, the effects that the wild-type
      protein elicits in tumorigenesis are poorly understood. Depending on the type of
      tissue, Ras proto-oncogenes appear to either promote or inhibit the tumor
      phenotype. In this report, we treated wild-type and N-ras knockout mice with 3
      methylcholanthrene (MCA) to induce fibrosarcomas and found that MCA is more
      carcinogenic in wild-type mice than in knockout mice. After injecting different
      doses of a tumorigenic cell line, the wild-type mice exhibited a shorter latency
      of tumor development than the knockouts, indicating that there are N-ras
      dependent differences in the stromal cells. Likewise, we have analyzed B-cell
      lymphomas induced by either N-methylnitrosourea or by the N-ras oncogene in mice
      that over-express the N-ras proto-oncogene and found that the over-expression of
      wild-type N-ras is able to increase the incidence of these lymphomas. Considered
      together, our results indicate that Ras proto-oncogenes can enhance or inhibit
      the malignant phenotype in vivo in different systems.

PMID- 14633662
TI  - Risk of non-medullary thyroid cancer influenced by polymorphic variation in the
      thyroglobulin gene.
AB  - Benign thyroid disorders are strong risk factors for non-medullary thyroid cancer
      (NMTC). Germline variation in Tg (thyroglobulin) and TSHR (thyroid stimulating
      hormone receptor) confers an increased risk of benign thyroid disorders. To
      explore the hypothesis that polymorphic variation in these genes affects the risk
      of NMTC we compared the frequency of TgQ2511R, TSHR-P52T and TSHR-D727E genotypes
      in two series of NMTC cases and controls (group 1, Canadian 102 cases and 102
      controls; group 2, British 202 cases and 298 controls). No significant
      association was seen with TSHR-P52T and TSHR-D727E genotypes and risk of NMTC.
      However, the frequency of the R-allele of TgQ2511R was over represented in NMTC
      cases in both study populations. The odds ratios associated with hetero- and
      homozygosity for the R-allele were 1.6 (95% confidence interval, 1.1-2.5) and 2.0
      (95% confidence interval, 1.2-3.3), respectively. Although the risk of NMTC
      associated with the TgQ2511R R-allele is modest, its high prevalence in the
      general population suggests it may make a significant contribution to the
      incidence of NMTC.

PMID- 14633663
TI  - IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the
      development of hepatocellular carcinoma in the rat.
AB  - Interferon (IFN)-alpha treatment is a common therapy for chronic viral hepatitis
      and contributes to preventing hepatocarcinogenesis. However, it is not clear
      whether IFN-alpha directly inhibits the clonal expansion of pre-neoplastic
      hepatocytes. To clarify the mechanism by which IFN-alpha prevents
      hepatocarcinogenesis, we examined the effect of IFN-alpha in a chemically induced
      hepatocarcinogenesis model initiated by diethylnitrosamine (DEN) and promoted by
      2-acetylaminofluorene (2-AAF) and partial hepatectomy, in which hepatocellular
      carcinoma (HCC) arises through pre-neoplastic foci without inflammation or
      fibrosis. The protocols of IFN-alpha administration were started simultaneously
      with chemical initiation and lasted for either 4 or 40 weeks. The pre-neoplastic
      foci and neoplastic HCC were evaluated at 4 or 40 weeks after chemical
      initiation, respectively. The effects of IFN-alpha were assessed by the
      expression of tumor-related genes and cell cycle-related genes in the pre
      neoplastic foci, using immunohistochemistry and reverse transcription-polymerase
      chain reaction (RT-PCR). As a result of IFN-alpha treatment, the numbers and
      average volume of pre-neoplastic foci were reduced. The proliferating cell
      nuclear antigen index and the expression of G(1) cyclins were also reduced in the
      pre-neoplastic foci in the IFN-treated group. The expression of p21, which is an
      inhibitor of cyclin-kinase complexes was higher in the foci of the IFN-treated
      group, while p53 expression was not altered in this group, compared with the
      control group. IFN-alpha also suppressed the tumor development at 40 weeks after
      initiation. And in the long-term IFN-alpha-treated group, both the tumor numbers
      and average tumor size were markedly more reduced than those in the short-term
      treated group. Therefore, it was demonstrated that longer treatment with IFN
      alpha was more effective, compared with shorter treatment. In conclusion, it was
      shown that IFN-alpha directly prevented and delayed hepatocarcinogenesis through
      the suppression of pre-neoplastic cell proliferation and that it may partially
      depend on p21 induction through a p53-independent pathway.

PMID- 14633664
TI  - Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian
      cells.
AB  - Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by
      inorganic arsenic, as demonstrated in our previous investigation, was evidenced
      by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements.
      Here we report the results of cytogenetic and morphological analyses performed on
      the progeny of cells dividing at the end of sodium arsenite treatment after they
      had been expanded through 120 generations (ASO cells) and then cloned. The
      acquired genetic instability persisted and was increased by highly unstable
      chromosomal rearrangements, namely dicentric chromosomes and telomeric
      associations, which were not seen following acute exposure. A peculiar finding
      was the preferential involvement of a particular chromosome in dicentric
      rearrangements observed in some isolated ASO clones. Interestingly, by
      immunostaining with anti-5-methylcytosine antibodies the genome-wide DNA
      hypomethylation, induced by arsenic immediately after the acute treatment, was
      found to affect those ASO clones characterized by aneuploidy and chromosomal
      rearrangements. These findings demonstrate that short-term exposure to arsenic
      has long-term effects and suggest that genome-wide DNA hypomethylation enhances
      genetic instability.

PMID- 14633665
TI  - The days and nights of cancer cells.
AB  - Biological clocks are intrinsic time-keeping systems that regulate behavior and
      physiological functions in most living organisms. Recent works in this area have
      addressed possible molecular links between the endogenous circadian clock and
      cell cycle regulation. In this review, by addressing how circadian clocks can
      interfere with the cell cycle and how the disruption of the circadian rhythm may
      cause defects in regulation of cell proliferation, we highlight this potential
      connection between circadian rhythm and cell cycle. We also discuss how the
      acquisition of recent data in circadian clock mechanism may help chronotherapy,
      which takes into account the biological time to improve cancer treatments, and
      may open new therapeutic avenues for treating circadian-related diseases.

PMID- 14633666
TI  - Mouse models to study the interaction of risk factors for human liver cancer.
AB  - Each of the risk factors for human liver cancer (aflatoxin exposure, hepatitis B
      virus-associated liver injury, p53 loss, p53ser249 mutation, and male sex) also
      increases the incidence of hepatocellular carcinoma (HCC) in mouse models of
      hepatocarcinogenesis. Neonatal mice, partially hepatectomized adult mice, and p53
      deficient mice each have a higher hepatocyte proliferation rate, are less able to
      detoxify AFB1, and form more DNA adducts than do normal wild-type controls.
      However, transgenic hepatitis B surface antigen mice, expressing hepatitis B
      surface antigen under control of the albumin promoter (alb/psx), are able to
      detoxify AFB1 at the same level as do wild-type mice. Thus, AFB1-induced HCC
      development in neonatal mice and p53+/- mice may be due to "immature" carcinogen
      metabolism, whereas increased HCC in transgenic hepatitis B virus mice may be due
      to promotion effects of increased proliferation. Future studies will explore the
      effects of modifying factors on the development of HCC.

PMID- 14633667
TI  - Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and
      reactivates methylation-silenced genes in cancer cell lines.
AB  - Hypermethylation of CpG islands in the promoter regions is an important mechanism
      to silence the expression of many important genes in cancer. The hypermethylation
      status is passed to the daughter cells through the methylation of the newly
      synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report
      herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from
      green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in
      cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine
      deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity,
      showing competitive inhibition with a K(i) of 6.89 microM. Studies with
      structural analogues of EGCG suggest the importance of D and B ring structures in
      the inhibitory activity. Molecular modeling studies also support this conclusion,
      and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265),
      Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of
      human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h
      caused a concentration- and time-dependent reversal of hypermethylation of
      p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine
      methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined
      by the appearance of the unmethylation-specific bands in PCR. This was
      accompanied by the expression of mRNA of these genes as determined by reverse
      transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was
      demonstrated by Western blot. Reactivation of some methylation-silenced genes by
      EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer
      KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the
      first time the inhibition of DNA methylation by a commonly consumed dietary
      constituent and suggest the potential use of EGCG for the prevention or reversal
      of related gene-silencing in the prevention of carcinogenesis.

PMID- 14633668
TI  - Novel magnetic resonance imaging contrasts for monitoring response to gene
      therapy in rat glioma.
AB  - Magnetic resonance imaging relaxation times, T(1rho) and Carr-Purcell T(2) (CP
      T(2)), were measured in a glioma herpes simplex virus-thymidine kinase gene
      therapy model. In treated tumors with >50% cell death by histology, T(1rho) and
      CP-T(2) measured with short spacing (tau(CP)) between centers of adiabatic
      refocusing pulses showed similar enhanced sensitivity to cytotoxic cell damage
      over CP-T(2) measured with long tau(CP) (long-tau(CP) T(2): 54.3 +/- 0.7 and 55.4
      +/- 1.2 ms, P = 0.30; short-tau(CP) T(2): 61.3 +/- 1.0 and 64.2 +/- 1.1 ms, P <
      0.05 before and day 2 of treatment, respectively). Without treatment, long
      tau(CP) T(2) provided the most pronounced contrast between tumor and normal
      cerebral tissue. These data demonstrate that endogenous T(2) contrast can be
      modulated and extended in a manner likely to be clinically important.

PMID- 14633669
TI  - Regulation of extracellular matrix metalloproteinase inducer and matrix
      metalloproteinase expression by amphiregulin in transformed human breast
      epithelial cells.
AB  - Amphiregulin (AR) and epidermal growth factor effects on expression and activity
      of the extracellular matrix metalloproteinase inducer (EMMPRIN) were examined in
      NS2T2A1 breast tumor cells. Both growth factors induced mRNA and protein
      expression of EMMPRIN, and matrix metalloproteinase (MMP) -2 and -9 enzymatic
      activity. The induction of EMMPRIN by AR was mediated by epidermal growth factor
      receptor (EGFR) tyrosine kinase activation and inhibited by ZD1839. AR and EGFR
      antisense (AS) cDNAs inhibited EMMPRIN expression and MMP activity. Coculture of
      NS2T2A1V expressing AR- or EGFR-AS with fibroblasts and endothelial cells showed
      a decreased MMP activity. In parallel, nude mice tumors derived from AR and EGFR
      AS cells revealed reduced level of EMMPRIN and MMP activity. AR and epidermal
      growth factor, therefore, regulate EMMPRIN and its MMP-mediated expression,
      identifying EGFR signaling as critical to this regulation.

PMID- 14633670
TI  - Pretreatment with 8-methoxypsoralen, a potent human CYP2A6 inhibitor, strongly
      inhibits lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone in female A/J mice.
AB  - Human CYP2A6 has been recognized as being involved in the mutagenic activation of
      promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to
      inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on
      NNK-induced lung tumorigenesis in female A/J mice were examined. Female A/J mice
      were treated with methoxsalen at doses of 50 or 12.5 mg/kg body weight, given by
      stomach tube, daily for 3 days. One h after the final treatment, NNK was injected
      i.p. at a dose of 2 mg/mouse. The experiments were terminated 16 weeks after the
      first methoxsalen treatment, and lung adenomas were analyzed. Pretreatment of
      methoxsalen significantly reduced tumor incidence from 93.8% to 16.7% (50 mg/kg)
      and 20.0% (12.5 mg/kg), and tumor multiplicity from 5.97 to 0.23 (50 mg/kg) and
      0.25 (12.5 mg/kg) tumors/mouse. These results clearly demonstrated that
      methoxsalen, a potent human CYP2A6 inhibitor, is a strong chemopreventive agent
      against NNK-induction of lung tumorigenesis.

PMID- 14633671
TI  - Treatment with the tumor necrosis factor-alpha-inducing drug 5,6
      dimethylxanthenone-4-acetic acid enhances the antitumor activity of the
      photodynamic therapy of RIF-1 mouse tumors.
AB  - DMXAA (5,6-dimethylxanthenone-4-acetic acid) is an antivascular agent that exerts
      its antitumor effect at least partly through the induction of tumor necrosis
      factor (TNF)-alpha. Photodynamic therapy (PDT), the activation of a photoreactive
      drug in tumor tissue with visible light, is used clinically to control solid
      malignancies. PDT has been shown previously to be potentiated, in mice, by the
      i.p. administration of recombinant human TNF-alpha. Here, we investigated the
      activity of DMXAA as a modifier of Photofrin-based PDT of implanted murine RIF-1
      tumors. The DMXAA dose (20 mg.kg(-1)) used throughout this study had little
      effect on tumor growth. The combination of DMXAA and PDT led to a reduction in
      tumor volume and significant delays in regrowth, giving a PDT-dose modification
      factor of 2.81. This enhancement was found to be strongly schedule dependent. The
      most pronounced responses were achieved when DMXAA was administered 1-3 h before
      the local illumination of the tumors; less activity was observed at other
      intervals within +/-24 h of PDT-light delivery. Using a 2-h DMXAA-light interval,
      histological examination showed significantly reduced blood vessel counts (CD31
      immunostaining) and marked necrosis (H&E) in the tumors given combination therapy
      compared with the tumors given either agent alone. Conversely, peritumoral tissue
      was still intact 24 h after the combined therapy. DMXAA did not augment the
      damage to normal mouse feet after low-dose PDT (1.5 mg.kg(-1) Photofrin);
      however, there was some enhancement of normal tissue phototoxicity when DMXAA was
      combined with high-dose PDT. The antitumor effect after DMXAA plus low-dose PDT
      (1.5 mg.kg(-1) Photofrin) appeared to be dependent on TNF-alpha because
      neutralizing antibodies to this cytokine reduced the tumor response to control
      levels. DMXAA by itself induced TNF-alpha in RIF-1 tumors whereas PDT did not.
      However, the addition of PDT after DMXAA resulted in decreases in TNF-alpha,
      suggesting that the enhanced antitumor activity of the combination therapy was
      not attributable simply to an increased induction of the cytokine by PDT over
      that from DMXAA alone. These observations suggest a promising new combination
      therapy with considerable therapeutic advantage.

PMID- 14633672
TI  - Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2
      expression in serous ovarian carcinoma.
AB  - Cyclooxygenase-2 (COX-2) expression has been shown to associate with poor
      prognosis in ovarian cancer, and an mRNA stability protein HuR has been shown to
      enhance expression of COX-2 in tissue culture conditions. We found cytoplasmic
      immunoreactivity for HuR protein in 52% (233 of 445) of serous-type ovarian
      carcinoma specimens, and it associated with high COX-2 expression (P = 0.0045)
      and with clinicopathological variables, including poor prognosis (P < 0.0001) and
      high grade (P < 0.0001). In ovarian cancer cells in vitro, a small interfering
      RNA against HuR and leptomycin B, an inhibitor of nucleocytoplasmic translocation
      of HuR, inhibited COX-2 expression. Our results show that cytoplasmic HuR
      expression associates with poor outcome in ovarian cancer, and one plausible
      explanation for this finding may be related to the ability of HuR to induce COX-2
      expression.

PMID- 14633673
TI  - Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway.
AB  - Colorectal carcinomas develop according to particular genetic pathways, including
      the chromosomal instability (CIN+), microsatellite instability (MSI+) and MSI-
      CIN- routes. We have determined the genetic pathway in patients with MYH
      associated polyposis (MAP), a syndrome of colorectal adenomas and cancer that
      results from defective base excision repair (BER). As in previous studies, MAP
      tumors showed a high frequency of G>T mutations in APC, in accordance with
      defective BER. We found that K-ras mutations were common in MAP tumors, all of
      the changes comprising conversion of the first guanine residue of codon 12 to
      thymidine (G12C, GGT>TGT). We found no BRAF mutations at the codon 599 hotspot or
      elsewhere in exon 14. Almost all of the MAP cancers were near-diploid (CIN-), and
      none was MSI+. A few p53 mutations were found, but these were not predominantly
      G>T changes. p53 overexpression was, however, frequent. No SMAD4 or TGFBIIR
      mutations were found. MAP tumors appear to follow a distinct genetic pathway,
      with some features of both the CIN and MSI pathways. BER deficiency is rarely
      accompanied by CIN or MSI. The spectrum of somatic mutations in MAP tumors
      reflects both selection and hypermutation to which certain guanine residues are
      particularly prone.

PMID- 14633674
TI  - The contribution of genetic and epigenetic mechanisms to gene silencing in
      oligodendrogliomas.
AB  - Very little is known of the genes and mechanisms contributing to the genesis of
      oligodendrogliomas, a subtype of primary brain tumors. Using an integrated
      genetic and epigenetic analysis of oligodendrogliomas, we show that aberrant CpG
      island methylation is the most prevalent alteration in these tumors, and the
      majority of methylated genes are independent of regions affected by deletion. In
      contrast, a subset of the gene-associated CpG islands are preferentially affected
      by converging methylation and deletion, including a putative zinc finger gene,
      ZNF342, located in a commonly deleted region at chromosome 19q13. ZNF342
      expression is specifically decreased in primary oligodendrogliomas and up
      regulated in glioma cell lines treated with a demethylating agent, whereas the
      expression level of the adjacent gene, Gemin7, is not consistently altered in
      these samples. This initial integrated approach identifies novel targets of gene
      silencing, and provides a more comprehensive view of the genes and mechanisms
      underlying oligodendrogliomas.

PMID- 14633675
TI  - Simian virus 40 sequences in malignant lymphomas in Japan.
AB  - Recent studies showed that SV40 is detected in >40% of non-Hodgkin's lymphoma
      (NHL) in United States, suggesting SV40-contaminated poliovaccines widely used
      during the period 1955-1963 to be a major source of SV40 in NHL. We examined the
      presence of SV40 sequences in 122 cases with NHL and 3 with Hodgkin's lymphoma
      from Japan. The detection rate of SV40 sequences in diffuse large B-cell lymphoma
      (19%) was higher than that in peripheral blood cells of normal healthy volunteers
      in Japan (4.7%; P < 0.05) reported previously as controls for comparison with the
      study results from cancer patients, suggesting a role for SV40 in the development
      of diffuse large B-cell lymphoma. In contrast, the frequency of SV40 sequences in
      NHL cases born between 1951 and 1963 (12%), during which SV40-contaminated
      poliovaccines might have been inoculated, is not significantly different from
      that in cases born before 1950 (11%) or after 1964 (15%). SV40 is a new candidate
      etiologic factor for malignant lymphoma not only in the United States but also in
      Japan.

PMID- 14633676
TI  - In vivo monitoring of capecitabine metabolism in human liver by 19fluorine
      magnetic resonance spectroscopy at 1.5 and 3 Tesla field strength.
AB  - In metastatic colorectal cancer the oral 5-fluorouracil (5FU) prodrug
      capecitabine is used with increasing frequency as an alternative to i.v. 5FU
      administration. The rate of conversion of capecitabine into 5'deoxy-5
      fluorouridine has been related to tumor response, and 5FU catabolites have been
      associated with 5FU-related systemic toxicity. Here we demonstrate for the first
      time that capecitabine, its metabolites 5'deoxy-5-fluorocytidine and 5'deoxy-5
      fluorouridine, and its catabolites 5-fluoro-ureido-propionic acid, alpha-fluoro
      beta-alanine, and alpha-fluoro-beta-alanine-bile acid conjugate can be monitored
      in vivo by (19)fluorine magnetic resonance spectroscopy ((19)F MRS) in the liver
      of patients with metastatic colorectal cancer. Moreover, we demonstrate an
      improved signal-to-noise ratio and spectral resolution of the (19)F MRS spectra
      when measurements are performed at 3 T field strength as compared with
      measurements at the common clinical field strength of 1.5 T. We conclude that
      assessment of capecitabine metabolism in patients by (19)F MRS is a promising
      noninvasive tool for the prediction of its efficacy and toxicity, especially at
      the now currently available clinical field strength of 3 T.

PMID- 14633677
TI  - Growth inhibition of human colon cancer cells by nitric oxide (NO)-donating
      aspirin is associated with cyclooxygenase-2 induction and beta-catenin/T-cell
      factor signaling, nuclear factor-kappaB, and NO synthase 2 inhibition:
      implications for chemoprevention.
AB  - Nitric oxide (NO)-releasing aspirin (ASA), consisting of a traditional ASA
      molecule to which a NO-donating moiety is covalently bound, is a promising colon
      cancer chemopreventive agent. NO-ASA inhibits colon cancer cell growth more
      potently than ASA by inhibiting cell proliferation and enhancing cell killing. We
      examined in cultured human colon cancer cells the effect of NO-ASA on the beta
      catenin/T-cell factor signaling pathway, nuclear factor-kappaB, and NO synthase 2
      and on cyclooxygenase (COX) expression, all presumed to participate in colon
      carcinogenesis. Besides inhibiting cell growth, NO-ASA inhibited the beta
      catenin/T-cell factor signaling pathway (IC(50), 1.1 microM), nuclear factor
      kappaB DNA binding (IC(50), 7.5 microM), and NO synthase 2 expression (IC(50), 2
      microM). Interestingly, NO-ASA induced COX-2 expression, although it had no
      effect on COX-1. COX-2 induction was accompanied by increased prostaglandin E(2)
      production. These effects occurred at NO-ASA concentrations below or near its
      IC(50) for cell growth (IC(50), 2-50 microM). The metabolism of NO-ASA by these
      cells is characterized by a rapid deacetylation step and the formation of a
      conjugate with glutathione. NO-ASA had no effect on intracellular cyclic GMP
      concentrations. We propose a model incorporating the pleiotropic effects of NO
      ASA on cell signaling and postulate that collectively these effects may
      contribute to its strong chemopreventive effect.

PMID- 14633678
TI  - Inactivation of a histone methyltransferase by mutations in human cancers.
AB  - Histone methyltransferase (HMT)(1) class enzymes that methylate lysine residues
      of histones or proteins contain a conserved catalytic core termed the SET domain,
      which shares sequence homology with an independently described sequence motif,
      the PR domain. Intact PR or SET sequence is required for tumor suppression
      functions, but it remains unclear whether it is histone methyltransferase
      activity that underlies tumor suppression. We now show that tumor suppressor RIZ1
      (PRDM2) methylates histone H3 on lysine 9, and this activity is reduced by
      mutations in the PR domain found in human cancers. Also, S-adenosylhomocysteine
      or methyl donor deficiency inhibits RIZ1 and other H3 lysine 9 methylation
      activities. These results support the hypothesis that H3 lysine 9 methylation
      activities of a PR/SET domain have tumor suppression functions and may underlie
      carcinogenesis associated with dietary methyl donor deficiency.

PMID- 14633679
TI  - Joint effect of estrogen receptor beta sequence variants and endogenous estrogen
      exposure on breast cancer risk in Chinese women.
AB  - Long-term estrogen exposure and family history of breast cancer are the two
      factors that are most consistently found to be associated with breast cancer
      risk. Sequence variants in genes involved in estrogen synthesis, metabolism, and
      signal transduction may account, in part, for this observation. Using data and
      DNA samples from the Shanghai Breast Cancer Study, we tested the hypothesis that
      sequence variants of the estrogen receptor beta gene (ESR2) may be associated
      with increased risk for breast cancer, particularly among women who have a high
      level and long-term endogenous estrogen exposure. Direct sequencing of the ESR2
      gene among 30 Chinese women revealed eight sequence variants. Association
      analysis of six common sequence variants in 1134 cases and 1235 controls provided
      evidence for positive associations between breast cancer risk and two single
      nucleotide polymorphisms (SNPs), [C(14206)T and C(33390)G], among postmenopausal
      women. Evidence of a stronger association was found for SNP [C(33390)G] among
      women with a long duration (> or =34 years) of menstruation (odds ratio, 2.37;
      95% confidence interval, 1.18-4.77). A potential synergistic effect between SNP
      [C(33390)G] and several steroid sex hormones was observed, and a 3-4-fold
      elevated risk of breast cancer was found among women with a CG or GG genotype in
      SNP [C(33390)G] combined with a high level of steroid sex hormone or a low level
      of sex hormone binding globulin. Our results are consistent with the hypothesis
      of a joint effect of estrogen receptor beta sequence variants and endogenous
      estrogen exposure on breast cancer risk.

PMID- 14633680
TI  - Enhancement of Bik antitumor effect by Bik mutants.
AB  - Bik was initially identified as a BH3-domain-only protein that interacts with E1B
      19K. Although systemically administered wild-type Bik significantly inhibited
      tumor growth and metastasis in an orthotopic nude mouse model, the proapoptotic
      potency of Bik can be modulated by posttranslational phosphorylation. Here, we
      found that Bik mutants, in which threonine 33 and/or serine 35 were changed to
      aspartic acid to mimic the phosphorylation at these two residues, enhanced their
      binding affinity with the antiapoptotic proteins Bcl-X(L) and Bcl-2 and were more
      potent than wild-type Bik in inducing apoptosis and inhibiting cell proliferation
      in various human cancer cells. Bik mutants also suppressed tumorigenicity and
      tumor-taking rate in a mouse ex vivo model. Moreover, Bik mutant-liposome
      complexes inhibited tumor growth and prolonged life span more effectively than
      the wild-type Bik-liposome complex in an in vivo orthotopic animal model. Thus,
      our results demonstrate that Bik mutant genes, more potent than wild-type Bik,
      induce cell death and suggest that their inhibition on the growth of various
      cancers should be explored further.

PMID- 14633681
TI  - Oxygenation gain factor: a novel parameter characterizing the association between
      hemoglobin level and the oxygenation status of breast cancers.
AB  - Tumor hypoxia has been linked to acquired treatment resistance, tumor
      progression, and poor prognosis. Because anemia is a major causative factor for
      the development of hypoxia, the association between blood hemoglobin
      concentration (cHb) and breast cancer oxygenation was examined in this study. In
      addition, a novel parameter characterizing the relationship between oxygenation
      status and rising cHb is introduced: the oxygenation gain factor (OGF). In breast
      cancer patients, median cHb over the range 8.5-14.7 g/dl correlated positively
      with the median pO(2) (3-15 mm Hg), yielding an average OGF of 2 mm Hg.dl/g. In
      contrast, in normal tissues (normal breast, subcutis, and skeletal muscle) the
      median pO(2) values were substantially higher (52 mm Hg, 51 mm Hg, and 37 mm Hg,
      respectively) and remained constant irrespective of the hemoglobin level over the
      range from 10 to 16 g/dl (OGF = 0 in grade I anemia and nonanemic patients).
      Moderately lower median pO(2) values in subcutis and skeletal muscle were only
      observed in grade II anemia (8 g/dl < cHb < or =10 g/dl), although this would
      appear to be of no biological relevance. Conversely, in breast cancers, even mild
      anemia (grade I anemia) is a major causative factor for the development of
      hypoxia or anoxia.

PMID- 14633682
TI  - p300 in prostate cancer proliferation and progression.
AB  - Although prostate cancer (PCa) is the most frequently diagnosed cancer in males,
      little is known about the mechanisms involved in its progression. Recent in vitro
      studies suggest that coactivators of the androgen receptor play an important role
      in PCa progression. We have shown previously that p300 is involved in androgen
      receptor transactivation. In the present work, we studied 95 patients with biopsy
      proven PCa who underwent prostatectomy as treatment of their tumors between 1995
      and 1998. We found that p300 correlated with in vivo proliferation (P = 0.009) as
      determined by MIB-I expression. Moreover, high levels of p300 in biopsies
      predicted larger tumor volumes (P < 0.001), extraprostatic extension (P = 0.003),
      and seminal vesicle involvement (P = 0.002) at prostatectomy, as well as PCa
      progression after surgery (P = 0.01). Furthermore, we found that the disruption
      of p300 transcripts through small interfering RNA inhibited PCa cell
      proliferation both at the basal level and on interleukin 6 stimulation. We
      conclude that p300 plays an important role in PCa cell proliferation, as well as
      PCa progression.

PMID- 14633683
TI  - DNA methylation in serum of breast cancer patients: an independent prognostic
      marker.
AB  - Changes in the status of DNA methylation are one of the most common molecular
      alterations in human neoplasia. Because it is possible to detect these epigenetic
      alterations in the bloodstream of patients, we investigated whether aberrant DNA
      methylation in patient pretherapeutic sera is of prognostic significance in
      breast cancer. Using MethyLight, a high-throughput DNA methylation assay, we
      analyzed 39 genes in a gene evaluation set, consisting of 10 sera from
      metastasized patients, 26 patients with primary breast cancer, and 10 control
      patients. To determine the prognostic value of genes identified within the gene
      evaluation set, we finally analyzed pretreatment sera of 24 patients having had
      no adjuvant treatment (training set) to determine their prognostic value. An
      independent test set consisting of 62 patients was then used to test the validity
      of genes and combinations of genes, which in the training set were found to be
      good prognostic markers. In the gene evaluation set we identified five genes
      (ESR1, APC, HSD17B4, HIC1, and RASSF1A). In the training set, patients with
      methylated serum DNA for RASSF1A and/or APC had the worst prognosis (P < 0.001).
      This finding was confirmed by analyzing serum samples from the independent test
      set (P = 0.007). When analyzing all 86 of the investigated patients, multivariate
      analysis showed methylated RASSF1A and/or APC serum DNA to be independently
      associated with poor outcome, with a relative risk for death of 5.7. DNA
      methylation of particular genes in pretherapeutic sera of breast cancer patients,
      especially of RASSF1A/APC, is more powerful than standard prognostic parameters.

PMID- 14633684
TI  - Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common fatal cancers in the
      world. However, the underlying molecular mechanisms contributing to
      hepatocarcinogenesis are still unclear. A putative tumor suppressor gene, namely
      DLC-1 (frequently deleted in liver cancer) was identified and mapped at
      chromosome 8p21.3-22, a recurrently deleted region in human cancers. The gene
      exerts inhibitory effects on the cell proliferation of HCC cells. In this study,
      we investigated the biological function, and genetic and epigenetic status of
      this gene in human HCC. With in vitro GTPase activating proteins activity assay,
      we established that DLC-1 protein was a GTPase-activating protein specific for
      RhoA and Cdc42. Deletion of the DLC-1 gene was frequent in human HCC, as revealed
      by loss of heterozygosity analysis performed on 100 human HCC cases with markers
      mapped at the DLC-1 locus, and allelic losses ranging from 44% to 50% of the
      informative cases. However, somatic mutations of the DLC-1 gene were rare.
      Moreover, with real-time quantitative PCR, we found that DLC-1 mRNA was
      significantly underexpressed in HCCs when compared with the corresponding
      nontumorous livers (P < 0.0001). In addition, the CpG island 5' to the DLC-1 gene
      was methylated in 3 of 7 HCC cell lines and in 6 (24%) of 25 primary HCCs. These
      data suggest that transcriptional silencing by hypermethylation may contribute to
      the inactivation of the DLC-1 gene. Taken together, the results of our study
      suggest that both genetic and epigenetic alterations play an important role in
      inactivation of the DLC-1 gene in hepatocarcinogenesis.

PMID- 14633685
TI  - Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell
      carcinoma of the bladder.
AB  - Deletions of the long arm of chromosome 9 are the most common genetic alteration
      in transitional cell carcinoma (TCC) of the bladder. Several regions of deletion
      on 9q have been mapped by loss of heterozygosity (LOH) analysis, one of which
      encompasses one of the two loci for tuberous sclerosis, TSC1, at 9q34. Tuberous
      sclerosis complex (TSC) is an autosomal dominant condition in which affected
      individuals develop benign tumors (hamartomas) in many organs. There is a small
      increase in risk of renal cell carcinoma (<2%), but the hamartomas are of stromal
      origin and patients do not develop an excess of epithelial malignancies. However,
      during a search for candidate bladder tumor suppressor genes within the 9q34
      region of LOH, we previously found a small number of mutations of TSC1, raising
      the possibility that this represents a bladder tumor suppressor. Here, we have
      carried out mutation analysis of 62 bladder tumors and 33 bladder tumor-derived
      cell lines to establish the frequency and spectrum of TSC1 mutations in TCC.
      Twelve percent of samples contained mutations. We found 10 somatic mutations, 9
      of which are novel mutations not found previously in TSC cases. Two of these were
      missense mutations, a type of change only rarely observed in the germ line in
      TSC. We also identified a bladder tumor patient carrying a germ-line mutation but
      with no symptoms of TSC. The tumor in this case and in two other cases with
      somatic mutations retained the wild-type allele. Thus 3 cases with mutation
      retained heterozygosity for TSC1 despite our selection of tumors mostly with 9q
      LOH (>80%) for the study. This may indicate that haploinsufficiency for TSC1 can
      contribute to the development of bladder cancer and, if so, that the LOH of TSC1
      observed in >50% of TCCs is biologically significant.

PMID- 14633686
TI  - High-resolution deletion mapping of 15q13.2-q21.1 in transitional cell carcinoma
      of the bladder.
AB  - Deletions found in several types of human tumor, including carcinomas of the
      colorectum, breast, and lung, suggest the presence of a potential tumor
      suppressor gene(s) on chromosome 15. Common regions of deletion in these tumors
      are at 15q15 and 15q21. Here, we have analyzed loss of heterozygosity (LOH) on
      chromosome 15 to ascertain its potential involvement in the development and
      progression of transitional cell carcinoma (TCC) of the bladder. A panel of 26
      polymorphic markers, spanning 15q12-15q22, were used to map regions of LOH in 51
      TCCs. LOH was found for at least one marker in the region 15q14-15q15.3 in 20 of
      51 (39%) tumors. Deletion mapping defined two minimum regions of deletion: a
      distal region between the markers D15S514 and D15S537 at 15q15.1-15q15.3
      (estimated as 3 Mb) and a more proximal region between the markers D15S971 and
      D15S1042 at 15q14 (estimated as 1.1 Mb). Analysis of a panel of 33 bladder tumor
      cell lines revealed regions of contiguous homozygosity for markers in 15q15,
      indicating likely LOH. Fluorescence in situ hybridization analysis demonstrated
      that mitotic recombination is the predicted mechanism of LOH in two of these.
      These regions of LOH on 15q may contain tumor suppressor genes the loss or
      inactivation of which is associated with TCC development. The DNA repair gene
      RAD51 at 15q15.1 represents a candidate 15q tumor suppressor gene. Expression
      analysis of rad51 protein in tumor cell lines revealed variable levels of
      expression but no significant loss of expression in cell lines with likely 15q
      LOH.

PMID- 14633687
TI  - Growth factor-independent activation of protein kinase B contributes to the
      inherent resistance of vascular endothelium to radiation-induced apoptotic
      response.
AB  - The phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (Akt) signal
      transduction pathway plays a critical role in mediating endothelial cell survival
      during oxidative stress. The role of the PI3K/Akt pathway in promoting cell
      viability was studied in vascular endothelial cells treated with ionizing
      radiation. Western blot analysis showed that Akt was phosphorylated rapidly in
      response to radiation in primary culture human umbilical vein endothelial cells
      in the absence of serum or growth factors. Akt phosphorylation occurred after
      doses as low as 1 Gy. PI3K consists of p85 and p110 subunits, which play a
      central role in Akt activation in response to exogenous stimuli. A mutation
      within the Src homology region 2 domain of mutant p85 (Deltap85) prevented
      radiation-induced Akt phosphorylation, when overexpressed in endothelial cells.
      Vascular endothelial cells transduced with control vector were resistant to
      radiation-induced apoptosis, whereas endothelial cell transduction with
      adenovirus encoding the mutated p85 (Ad.Deltap85) reversed this resistance to
      apoptosis after treatment with intermediate radiation doses (2-6 Gy). Deltap85
      overexpression alone had no effect on the viability or apoptosis of endothelial
      cells. However, irradiated endothelial cells overexpressing Deltap85 released
      cytochrome c into the cytosol fraction and activated proteolytic cleavage of
      caspases 3 and 9, thereby inducing the apoptotic response. Inhibition of caspase
      3 blocked endothelial apoptosis induced by overexpression of Deltap85 and
      radiation. These findings suggest that growth factor-independent activation of
      Akt contributes, in part, to the inherent resistance of irradiated vascular
      endothelium to the activation of apoptotic response.

PMID- 14633688
TI  - Loss of protein phosphatase 2A expression correlates with phosphorylation of DP-1
      and reversal of dysplasia through differentiation in a conditional mouse model of
      cancer progression.
AB  - A conditional mouse model of time-dependent dysplasia reversal demonstrated that
      reversal and differentiation of dysplastic salivary gland tissue at the 4-month
      reversible stage was characterized by the appearance of a phosphorylated slower
      mobility form of Differentiation Related Transcription Factor 1-polypeptide-1
      that was correlated with cellular differentiation. The phosphorylated form of DP
      1 was not found at the 7-month irreversible stage or in adenocarcinomas. At the 4
      month reversible stage, protein phosphatase 2A expression was down-regulated
      coincident with loss of oncogene expression, whereas PP2A expression persisted at
      the 7-month irreversible stage. Results are consistent with the hypothesis that
      persistent PP2A expression prevented the appearance of the phosphorylated form of
      DP-1 required for cellular differentiation and reversal of dysplasia after loss
      of oncogene expression.

PMID- 14633689
TI  - Stem cell factor receptor (c-KIT) codon 816 mutations predict development of
      bilateral testicular germ-cell tumors.
AB  - Testicular germ-cell tumors (TGCTs) of adolescents and adults originate from
      intratubular germ cell neoplasia (ITGCN), which is composed of the malignant
      counterparts of embryonal germ cells. ITGCN cells are characterized, among
      others, by the presence of stem cell factor receptor c-KIT. Once established,
      ITGCN will always progress to invasiveness. Approximately 2.5-5% of patients with
      a TGCT will develop bilateral disease and require complete castration, resulting
      in infertility, a need for lifelong androgen replacement, and psychological
      stress. To date, the only way to predict a contralateral tumor is surgical biopsy
      of the contralateral testis to demonstrate ITGCN. We did a retrospective study of
      224 unilateral and 61 proven bilateral TGCTs (from 46 patients, in three
      independently collected series in Europe) for the presence of activating c-KIT
      codon 816 mutations. A c-KIT codon 816 mutation was found in three unilateral
      TGCT (1.3%), and in 57 bilateral TGCTs (93%; P < 0.0001). In the two wild-type
      bilateral tumors for which ITGCN was available, the preinvasive cells contained
      the mutation. The mutations were somatic in origin and identical in both tumors.
      We conclude that somatic activating codon 816 c-KIT mutations are associated with
      development of bilateral TGCT. Detection of c-KIT codon 816 mutations in
      unilateral TGCT identifies patients at risk for bilateral disease. These patients
      may undergo tailored treatment to prevent the development of bilateral disease,
      with retention of testicular hormonal function.

PMID- 14633690
TI  - Small interfering RNA-mediated reduction in heterogeneous nuclear
      ribonucleoparticule A1/A2 proteins induces apoptosis in human cancer cells but
      not in normal mortal cell lines.
AB  - To prevent their recognition as DNA breaks, the ends of linear chromosomes are
      organized into telomeres, which are made of proteins bound to telomere-specific,
      double-stranded repeats and to single-stranded DNA extensions, the G-tails. The
      mammalian heterogeneous nuclear ribonucleoparticule A1 and A2 proteins can bind
      with high affinity to such G-tails. Moreover, previous work established that in
      certain mouse cells a severe reduction in the level of A1 is associated with
      shortened telomeric repeat tracts, and restoring A1 expression increases telomere
      length. Here, we document that the expression of A1/A2 proteins is elevated in a
      variety of human cancers, whereas A1/A2 expression is lower or absent in normal
      tissues. To determine whether the status of A1/A2 proteins could be improved from
      cancer markers to cancer targets, we used small interfering RNA-mediated RNA
      interference to elicit a reduction in A1/A2 proteins in a variety of human cell
      lines. We show that this treatment provoked specific and rapid cell death by
      apoptosis in cell lines derived from cervical, colon, breast, ovarian, and brain
      cancers. Cancer cell lines that lack p53 or express a defective p53 protein were
      equally sensitive to a small interfering RNA-mediated decrease in A1/A2
      expression. The reduction in A1/A2 levels in HeLa cells was associated with a
      change in the distribution of the lengths of G-tails, an event not observed when
      apoptosis was induced with staurosporine. Remarkably, comparable decreases in the
      expression of A1/A2 in several mortal human fibroblastic and epithelial cell
      lines did not promote cell death. Thus, manipulating the level and activity of
      A1/A2 proteins may constitute a potent and specific approach in the treatment of
      human cancers of various origins.

PMID- 14633691
TI  - Inhibitor of nuclear factor kappaB kinase deficiency enhances oxidative stress
      and prolongs c-Jun NH2-terminal kinase activation induced by arsenic.
AB  - Stress signals activate both inhibitor of nuclear factor-kappaB kinase (IKKbeta)
      and c-Jun NH(2)-terminal kinase (JNK). It was shown recently that IKK-dependent
      nuclear factor kappaB activation results in attenuation of tumor necrosis factor
      alpha-induced JNK activation. How that negative cross-talk between nuclear factor
      kappaB and JNK occurs is not well-understood. By using wild-type and Ikkbeta gene
      knockout (Ikkbeta(-/-)) mouse embryo fibroblasts, we found that IKKbeta
      deficiency results in prolongation of arsenic-induced JNK activation, which was
      not due to the decreased expression of GADD45beta or X-linked Inhibitor of
      Apoptosis (XIAP), as suggested previously for RelA(-/-) cells treated with tumor
      necrosis factor alpha. This enhanced JNK activation was largely associated with
      an oxidative stress response as indicated by elevated expression of heme
      oxygenase-1 and the accumulation of H(2)O(2) in Ikkbeta(-/-) cells. Expression
      profiling experiments revealed an increased expression of p450 family CYP1B1 mRNA
      in Ikkbeta(-/-) cells compared with wild-type cells. Inhibition of CYP1B1 reduced
      both oxidative stress and arsenic-stimulated JNK activation. Thus, increased
      CYP1B1 expression is central to and seems to be responsible for sensitizing
      Ikkbeta(-/-) cells to stress-induced JNK activation.

PMID- 14633692
TI  - Death-associated protein kinase promoter hypermethylation in normal human
      lymphocytes.
AB  - A high frequency of death-associated protein kinase (DAPK) promoter
      hypermethylation has been noted in B-cell malignancies, head and neck cancers,
      and other solid tumors, and it has been used as a tumor marker in molecular
      detection strategies. Low levels of DAPK promoter hypermethylation, ranging from
      0.003 to 1.181%, were detected in peripheral blood cells from 75 of 143 (52%)
      normal subjects by quantitative methylation-specific PCR (Q-MSP). In 10 of 10
      selected patients, MSP amplification of a portion of the DAPK promoter followed
      by PCR product sequencing confirmed dense hypermethylation of the CpG island in
      their peripheral blood cells. Q-MSP analysis of fluorescence-activated cell
      sorted peripheral blood cells from three of these patients demonstrated that a
      significantly greater proportion of B cells (1.074-6.026%) were DAPK
      hypermethylated than were T cells, monocytes, or neutrophils, which were <0.06%
      hypermethylated. Further analysis after sorting of one subject's B cells into
      IgM+, IgM-, IgG+, and IgG- subpopulations demonstrated that DAPK hypermethylation
      was predominantly present in the IgM- compared with IgM+ B cells (3.338% versus
      0.436%). DAPK promoter hypermethylation was found in IgM- B cells in normal
      individuals. The same hypermethylation identified in B-cell malignancies may
      reflect a clonal outgrowth of B cells arising from this compartment and may
      indicate a susceptibility to neoplastic transformation in a subset of B cells.
      Normal circulating lymphocytes with DAPK promoter hypermethylation may act as
      confounding factors in tumor detection based on DAPK hypermethylation.

PMID- 14633693
TI  - Increased formation and persistence of 1,N(6)-ethenoadenine in DNA is not
      associated with higher susceptibility to carcinogenesis in alkylpurine-DNA-N
      glycosylase knockout mice treated with vinyl carbamate.
AB  - Ethenobases are promutagenic DNA adducts formed by some environmental carcinogens
      and products of endogenous lipid peroxidation. Mutation spectra in tumors induced
      in mice by urethane or its metabolite vinyl carbamate (Vcar) are compatible with
      1,N(6)-ethenoadenine (epsilonA) being an initiating lesion in the development of
      these tumors. As alkylpurine-DNA-N-glycosylase (APNG) releases epsilonA from DNA
      in vitro, wild-type and APNG-/- C57Bl/6J mice were treated with Vcar and levels
      of epsilonA and 3,N(4)-ethenocytosine (epsilonC), which is not a substrate of
      APNG, were analyzed in liver and lung DNA. At 6 h after the last dose, levels of
      epsilonA were 1.6-fold higher in DNA from APNG-/- mice and subsequently persisted
      at higher levels for longer than in DNA from wild-type animals, confirming that
      epsilonA is released by APNG in vivo. In contrast, approximately 14-fold lower
      levels of epsilonC were induced by Vcar, and the kinetics of formation and
      persistence of epsilonC was similar in the two mouse strains. The carcinogenicity
      of Vcar was compared in APNG-/- and wild-type suckling mice given a single dose
      of Vcar (30 or 150 nmol/g). After 1 year, only mice in the high-dose group
      developed hepatocellular carcinoma; however, the incidence was not higher in APNG
      /- mice. Although higher levels and increased persistence of epsilonA was
      observed in hepatic DNA from APNG-/- mice at 150 nmol/g Vcar, apoptosis and cell
      proliferation levels were similar in both strains of mice. This may explain why
      differences in epsilonA formation/persistence observed here did not result in
      higher susceptibility of APNG-/- mice to hepatocarcinogenesis.

PMID- 14633694
TI  - Evidence of alterations in base excision repair of oxidative DNA damage during
      spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats.
AB  - The Long-Evans Cinnamon (LEC) rat, an animal model for Wilson's disease, is an
      inbred mutant strain, which because of the genetic copper metabolism disorder
      develops hepatitis approximately 4 months after birth, followed by chronic
      hepatitis later in life, and eventually all of the surviving animals from liver
      injury and hepatitis develop spontaneous hepatocellular carcinomas. This animal
      model also shows that the generation of reactive oxygen species and the
      accumulation of oxidative damage in the liver DNA has significantly increased
      over the lifetime of LEC versus the wild-type Long-Evans Agouti (LEA) rats. Thus,
      the LEC rats having this genetically induced oxidative condition are proved to be
      very useful model for the study of endogenous DNA lesions and their relation to
      spontaneous carcinogenesis. In this study, we tested the hypothesis that
      differences do exist between these two rat strains in respect to their capacity
      to repair oxidative DNA base modification, which could explain the elevation of
      endogenous oxidative damage in the LEC rat liver DNA. We found that both the
      activity and expression at the protein and RNA levels of major DNA glycosylases,
      endonuclease III and 8-oxoguanine DNA-glycosylase, which initiate the excision
      and repair of oxidized bases, were significantly altered during the acute (16-18
      weeks) and early chronic (24 weeks) phases of hepatitis. Enzyme levels were
      restored in the later period of chronic hepatitis (week 40) in the LEC rat liver
      as compared with the age-matched LEA rats. This early reduction in the capacity
      to repair oxidative DNA base damage could have contributed to the accumulation of
      mutagenic adducts in liver DNA. These findings show for the first time in an
      animal model that acute hepatitis impairs the repair of oxidative DNA base damage
      and strongly suggest that the repair of endogenous DNA adducts plays a critical
      role in the development of spontaneous hepatocellular carcinoma in LEC rats.

PMID- 14633695
TI  - Insulin-like growth factor 1 receptor enhances invasion and induces resistance to
      apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway.
AB  - Colon cancer overexpresses insulin-like growth factor 1 (IGF1) and insulin-like
      growth factor 1 receptor (IGF1-R), as compared with normal or adenomatous mucosa,
      and it has been postulated that colorectal cancer cells depend on the IGF1/IGF1-R
      pathway for their growth and progression. In this study, using the human colon
      cancer cell line HCT116, we find that established HCT116/IGF1-R transfectants
      exhibit a more aggressive transformed phenotype than the parental cell line, as
      demonstrated by their higher proliferation rate in response to IGF1, higher
      degree of anchorage-independent growth, resistance to serum deprivation-induced
      apoptosis, and higher migratory capability in a monolayer "wounding assay." When
      injected into nude mice, HCT116/IGF1-R transfectants were highly invasive and
      produced distant metastases, whereas the parental cell did not. Moreover, the
      overexpression of IGF1-R in these cells was associated with IGF1-R-induced
      activation of Akt and up-regulation of the antiapoptotic protein Bcl-x(L). We
      also show that Akt pathway mediates IGF1-R-induced Bcl-x(L) expression at
      transcriptional level. Our data demonstrate, for the first time, that IGF1
      R/Akt/Bcl-x(L) pathway may contribute to a more aggressive malignant phenotype,
      in a subset of colorectal cancers.

PMID- 14633696
TI  - Restoration of insulin-like growth factor binding protein-related protein 1 has a
      tumor-suppressive activity through induction of apoptosis in human prostate
      cancer.
AB  - Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), a
      member of the IGFBP super family, is down-regulated at the mRNA level in several
      solid cancers. We hypothesize that IGFBP-rP1 has a tumor-suppressive effect on
      prostate cancer growth and its inactivation is through CpG hypermethylation. We
      tested this hypothesis through expression analysis of IGFBP-rP1, transfection
      studies, growth analysis, and CpG methylation in prostate cancer cells and
      tissues. In situ hybridization revealed IGFBP-rP1 mRNA expression was detected in
      the stroma and epithelium of benign prostatic hyperplasia tissues but was either
      weak or lost in prostate cancer tissues. The mRNA expression for IGFBP-rP1 was
      lacking in DU145, LNCaP, ND-1, and PC-3 prostate cancer cell lines, and after
      demethylation (5-aza-dC treatment), the expression was restored suggesting that
      methylation inactivated IGFBP-rP1 expression in prostate cancer cells. We further
      tested whether transfection of IGFBP-rP1 can modulate prostate cancer cells
      growth. We transfected PC-3 cell lines with IGFBP-rP1 cDNA (PC-3-rP1) and
      Northern blotting confirmed mRNA transcript of IGFBP-rP1 in these PC-3-rP1
      clones. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      showed growth rate was significantly lower in PC-3-rP1 cells than in the
      nontransfected control. In addition, the medium obtained from PC-3-rP1 cells
      reduced the growth rate in both PC-3-rP1 and control PC-3 cells. A soft agar
      colony-forming assay revealed that colony formation was markedly decreased in PC
      3-rP1 cells. The number of apoptotic cells and caspase-3 expression were
      increased in the PC-3-rP1 cells as compared with control PC-3 cells. This is the
      first study that suggests inactivation of IGFBP-rP1 is through CpG methylation,
      and tumor-suppressive activity of IGFBP-rP1 is through induction of apoptosis in
      an IGF-I independent manner in prostate cancer.

PMID- 14633697
TI  - Suppression of survivin expression inhibits in vivo tumorigenicity and
      angiogenesis in gastric cancer.
AB  - Survivin plays an important role in cancer development. We aim to show here that
      suppression of survivin expression or function by antisense and dominant-negative
      (DN) mutant can inhibit gastric cancer carcinogenesis and angiogenesis in vivo.
      Plasmid constructs expressing survivin antisense and DN mutant replacing the
      cysteine residue at amino acid 84 with alanine (Cys84Ala) were prepared and
      introduced into BCG-823 and MKN-45 gastric cancer cells to establish stable
      transfectants. We showed that both antisense and DN mutant stable transfectants
      exhibited abnormal morphology, with decreased cell growth and increased rate of
      spontaneous apoptosis and mitotic catastrophe. Furthermore, in nude mice
      xenografts, these cells exhibited decreased de novo gastric tumor formation and
      reduced development of angiogenesis. Results from these studies strongly suggest
      that survivin is a promising target for gastric cancer treatment.

PMID- 14633698
TI  - Heparanase affects adhesive and tumorigenic potential of human glioma cells.
AB  - Heparanase is an endo-beta-glucuronidase responsible for the cleavage of heparan
      sulfate, participating in extracellular matrix degradation and remodeling.
      Traditionally, heparanase activity was well correlated with the metastatic
      potential of a large number of tumor-derived cell types. More recently,
      heparanase up-regulation was detected in essentially all human tumors examined,
      correlating, in some cases, with poor postoperative survival and increased tumor
      vascularity. The role of heparanase in primary tumor progression is, however,
      poorly understood. Here, we overexpressed the human heparanase gene in a human
      glioma cell line, U87. We found that heparanase overexpression induces cell
      invasion, as might be expected. Surprisingly, elevated heparanase expression
      levels correlated with decreased proliferation rates and increased cell spreading
      and formation of a tight monolayer rather than large cell aggregates. This
      phenotypic appearance was accompanied by beta1-integrin activation, FAK and Akt
      phosphorylation, and Rac activation. In a xenograft tumor model, relatively
      moderate heparanase expression levels significantly enhanced tumor development
      and tumor vascularity, whereas high heparanase expression levels inhibited tumor
      growth. These results indicate that heparanase activates signal transduction
      pathways and, depending on its expression levels, may modulate tumor progression.

PMID- 14633699
TI  - Neuroblastoma-derived sulfhydryl oxidase, a new member of the sulfhydryl
      oxidase/Quiescin6 family, regulates sensitization to interferon gamma-induced
      cell death in human neuroblastoma cells.
AB  - In neuroblastoma cells, apoptotic programs can be activated by cytokines and
      cytostatic drugs. Apoptotic dysfunction confers resistance against therapeutic
      drugs and is a major complication for achieving optimal therapy response.
      Deregulated expression of the MYCN gene is a critical determinant in
      neuroblastoma progression, and one of the pleiotropic functions of the MYCN
      protein is cellular sensitization to cytokine-induced and drug-induced apoptosis.
      By using the functional approach of technical knockout (TKO), we have identified
      five genes that regulate sensitization for IFN-gamma-induced cell death. Most
      efficient among them is the newly identified SOXN (neuroblastoma-derived
      sulfhydryl oxidase), which comprises 12 exons and maps to 9q34.3. SOXN encodes a
      putative protein of 698 amino acids that contains a signal sequence, a protein
      disulfide-isomerase-type thioredoxin and a yeast ERV1 domain and is highly
      homologous to members of the sulfhydryl oxidase/Quiescin6 family. The SOXN
      protein is predominantly located in the plasma and in the nuclear membrane.
      Antisense SOXN confers resistance to IFN-gamma-induced apoptosis. In contrast,
      ectopic overexpression of sense-SOXN sensitizes the cells to induced cell death.
      These results identify SOXN as a major player in regulating the sensitization of
      neuroblastoma cells for IFN-gamma-induced apoptosis.

PMID- 14633700
TI  - Reduced hepatocyte proliferation is the basis of retarded liver tumor progression
      and liver regeneration in mice lacking N-acetylglucosaminyltransferase III.
AB  - Mice lacking N-acetylglucosaminyltransferase III (GlcNAc-TIII) exhibit slightly
      but significantly retarded liver tumor progression after a single injection of 10
      micro g/g diethylnitrosamine (DEN) and continued administration of phenobarbital
      (PB) in drinking water. A key question is whether the absence of GlcNAc-TIII
      inhibits cell proliferation or induces apoptosis. Because PB aids tumor
      progression, we tested whether it diminished the difference in tumor progression
      between Mgat3(+/+) and Mgat3(Delta/Delta) mice. Here, we show that in the absence
      of PB, control males developed about twice as many liver tumor nodules as males
      lacking GlcNAc-TIII. Both the size of liver tumors and liver weights were
      significantly greater in DEN-treated wild-type or heterozygous mice. Apoptosis
      assays performed monthly after DEN treatment showed no differences between mutant
      and wild-type. However, there was a marked retardation in liver regeneration
      after partial (70%) hepatectomy (PH). Wild-type mice incorporated
      bromodeoxyuridine in approximately 15% of hepatocyte nuclei at 48 h after PH,
      whereas mice lacking GlcNAc-TIII had only approximately 5% positive nuclei. This
      was not because of enhanced apoptosis in mutant mice after PH. Expression of the
      Mgat3 gene remained undetectable in wild-type liver by Northern analysis after
      tumor induction or after PH. In addition, transgenic overexpression of GlcNAc
      TIII in hepatocytes did not enhance tumor progression in Mgat3(Delta/Delta) mice,
      and there were no differences in tumor progression or liver regeneration after PH
      between control and transgenic mice overexpressing GlcNAc-TIII in liver.
      Therefore, the nonhepatic action of GlcNAc-TIII promotes hepatocyte proliferation
      after PH, as well as the progression of DEN-induced tumors, providing evidence
      for a functional role of the bisecting GlcNAc on circulating glycoprotein growth
      factor(s) that stimulate hepatocyte proliferation.

PMID- 14633701
TI  - Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion
      in a mouse model for squamous cell carcinoma.
AB  - Smad7 and Smad6 are inhibitory Smads that block transforming growth factor-beta
      (TGF-beta) superfamily signal transduction. Smad7 is overexpressed in chemically
      induced mouse epidermal tumors, where oncogenic activation of c-ras is a frequent
      event. To test the role of Smad7 overexpression in tumor progression, we used
      retroviruses to transduce Smad7 or Smad6 and v-ras(Ha) into primary mouse
      keratinocytes. By itself, Smad7 transiently enhanced keratinocyte proliferation,
      blocked normal differentiation, and induced keratin 8, a marker of malignant
      conversion, but did not cause tumor formation. Smad7 extended the in vitro life
      span, suppressed senescence, and increased transformation frequency 3-fold of
      primary keratinocytes coexpressing v-ras(Ha). Smad7/v-ras(Ha) coinfected
      keratinocytes rapidly progressed to squamous cell carcinomas in vivo, whereas
      pBabe/v-ras(Ha)- or Smad6/v-ras(Ha)-transduced keratinocytes formed only benign
      papillomas. Smad7/v-ras(Ha) tumors had elevated proliferation and defective
      nuclear localizaton of Smad2, Smad3, and Smad5, whereas only Smad5 was altered in
      Smad6/v-ras(Ha) tumors. Smad7 overexpression in vitro induced epidermal growth
      factor (EGF)-like growth factors TGF-alpha, heparin binding-EGF, amphiregulin,
      and EGF receptor tyrosine phosphorylation as well as the EGF-CFC growth factor
      cripto-1. TGF-alpha and cripto-1 were also overexpressed in Smad7/v-ras(Ha)
      tumors. These results suggest that Smad7 overexpression accelerates tumor
      progression through inhibition of TGF-beta superfamily signaling and up
      regulation of the EGF-like superfamily of growth factors. This is the first
      demonstration that Smad7 overexpression can cause malignant conversion in a
      multistage cancer model and suggests that it may have an important role in the
      pathogenesis of human cancer.

PMID- 14633702
TI  - Aberrant expression and localization of decorin in human oral dysplasia and
      squamous cell carcinoma.
AB  - The small leucine-rich proteoglycan decorin has been associated with negative
      regulation of cell growth. It has a prominent role in transforming growth factor
      (TGF)-beta and epidermal growth factor receptor activation pathways that
      contributes to its role in cellular proliferation, angiogenesis, and
      immunomodulation. Our studies are directed toward analysis of decorin gene
      expression, identified through DNA microarray studies, in oral premalignant and
      malignant tissues as well as representative cell lines of an oral cancer
      progression model. We have used long oligonucleotide microarray analysis,
      immunohistochemistry, confocal microscopy, reverse transcription-PCR, sequencing,
      and Western immunoblot techniques to characterize decorin expression in oral
      premalignant archival tissues and an oral cancer progression cellular model. We
      have further analyzed the deduced amino acid sequence derived from full-length
      cDNA that do not show any deletion or mutations of the decorin expressed in oral
      premalignant and malignant cell lines. In our studies, we show aberrant
      expression of decorin in dysplastic oral epithelial cells. Both promoters P1 and
      P2 drive the aberrant expression resulting in exon 1a as well as exon 1b carrying
      transcripts. Intracellular accumulation and nuclear localization of aberrantly
      expressed decorin were observed in dysplastic oral tissues and in the respective
      cell lines. Decorin expressed in oral cancer may have lost its ability to inhibit
      TGF-beta signaling and activate epidermal growth factor receptor signaling
      pathways because of such aberrant nuclear localization, resulting in a major
      dysfunction of otherwise a natural extracellular antagonist of TGF-beta and a
      putative tumor suppressor protein. The aberrant nuclear localization of a leucine
      rich repeat protein might result in additional protein-protein interactions and
      resulting changes in gene expression. Further studies to characterize such
      interacting proteins and localization-dependent effects of aberrant decorin
      expressed in oral cancer progression are warranted.

PMID- 14633703
TI  - The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839
      promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2
      overexpressing breast cancer cells.
AB  - AKT, a serine/threonine kinase that promotes cell survival, can be activated by
      overexpression of the receptor tyrosine kinase ErbB2. Conversely, down-regulation
      of ErbB2 inhibits AKT activation. Here, we identify PP1 as a serine/threonine
      phosphatase that associates with and dephosphorylates AKT in breast cancer cells,
      and we show that ErbB2 inhibits PP1-dependent dephosphorylation of AKT.
      Inhibition of ErbB2 by either the HSP (heat shock protein) 90 inhibitor
      geldanamycin or the ErbB inhibitor ZD1839 in SKBR3 cells, a human breast cancer
      cell line overexpressing ErbB2 protein, induces a rapid and dramatic decrease in
      AKT activity. Decreased AKT activity occurs many hours before the HSP90-dependent
      decline of AKT protein but is correlated with loss of AKT phosphorylation.
      Decreased AKT phosphorylation is not due to blockade of AKT activation or to
      preferential HSP90-mediated degradation of phosphorylated AKT. Instead, it is
      caused by increased AKT dephosphorylation. Sensitivity to a panel of phosphatase
      inhibitors suggests involvement of the phosphatase PP1 in this process. In vitro
      phosphatase assay (using PP1 immunoprecipitated from COS7 cells transiently
      transfected with the wild-type protein, as well as purified PP1) confirmed that
      AKT is a substrate of PP1. Furthermore, endogenous PP1 and AKT associate with
      each other in SKBR3. However, the phosphatase is phosphorylated and its activity
      is suppressed (determined by in vitro assay). In contrast, ErbB2 inhibition
      abrogates PP1 phosphorylation and restores its activity (measured by its ability
      to dephosphorylate AKT in vitro). Finally, transient overexpression of
      constitutively active PP1 in SKBR3 cells promotes marked dephosphorylation of
      endogenous AKT protein. These data indicate that ErbB2 acts to preserve the
      phosphorylation, and hence to prolong the activation, of AKT kinase by repressing
      the activity of the phosphatase PP1. ErbB2 thus functions to regulate AKT kinase
      by simultaneously promoting its activation while inhibiting its inactivation.

PMID- 14633704
TI  - Determination of clonality of metastasis by cell-specific color-coded fluorescent
      protein imaging.
AB  - It has been thought that metastases are clonal and originate from rare cells in
      primary tumors that are heterogeneous in genotype and phenotype. Recent studies
      using DNA array analysis challenge this hypothesis and suggest the genetic
      background of the host is the important determinant of metastatic potential
      implying that metastases are not necessarily clonal. Previous methods to
      determine clonality of metastasis used karyotype or molecular analysis that were
      complicated, thereby limiting the number of metastatic colonies analyzed and the
      conclusions that could be drawn. We describe here the use of green fluorescent
      protein-labeled or red fluorescent protein-labeled HT-1080 human fibrosarcoma
      cells to determine clonality by simple fluorescence visualization of metastatic
      colonies after mixed implantation of the red and green fluorescent cells.
      Resulting pure red or pure green colonies were scored as clonal, whereas mixed
      yellow colonies were scored as nonclonal. In a spontaneous metastasis model
      originating from footpad injection in severe combined immunodeficient mice, 95%
      of the resulting lung colonies were either pure green or pure red, indicating
      monoclonal origin, whereas 5% were of mixed color, indicating polyclonal origin.
      In an experimental lung metastasis model established by tail vein injection in
      severe combined immunodeficient mice, clonality of lung metastasis was dependent
      on cell number. With a minimum cell number injected, almost all (96%) colonies
      were pure red or green and therefore monoclonal. When a large number of cells
      were injected, almost all (87%) colonies were mixed color and therefore
      heteroclonal. We conclude that spontaneous metastasis may be clonal because they
      are rare events, thereby supporting the rare-cell clonal origin of metastasis
      hypothesis. The clonality of the experimental metastasis model depended on the
      number of input cells. The simple fluorescence method of determining clonality of
      metastases described here can allow large-scale clonal analysis in numerous types
      of metastatic models.

PMID- 14633705
TI  - SB-431542 and Gleevec inhibit transforming growth factor-beta-induced
      proliferation of human osteosarcoma cells.
AB  - Transforming growth factor-beta (TGF-beta) has growth-stimulating effects on
      mesenchymal cells and several tumor cell lines. The signaling pathway for this
      effect is, however, not well understood. We examined how TGF-beta stimulates
      proliferation of MG63 human osteosarcoma cells. Two distinct type I receptors for
      TGF-beta, ALK-1 and ALK-5, were expressed and functional in MG63 cells. Of these
      two receptors, ALK-5 appears to be responsible for the growth stimulation because
      expression of constitutively active ALK-5, but not ALK-1, stimulated
      proliferation of MG63 cells. SB-431542 (0.3 microM), a novel inhibitor of
      ALK4/5/7 kinase, suppressed TGF-beta-induced growth stimulation. DNA microarray
      analysis as well as quantitative real-time PCR analysis of RNAs from TGF-beta
      treated cells demonstrated that several growth factors, including platelet
      derived growth factor AA, were induced in response to TGF-beta in MG63 cells.
      Gleevec (1 microM) as well as AG1296 (5 microM) inhibited TGF-beta-induced growth
      stimulation of MG63 cells, suggesting that platelet-derived growth factor AA was
      mainly responsible for the growth-stimulatory effect of TGF-beta. We also
      examined the mechanisms of perturbation of growth-suppressing signaling in MG63
      cells. We found that expression of c-Myc, which is down-regulated by TGF-beta in
      many other cells, was up-regulated in MG63 cells, suggesting that up-regulation
      of c-Myc expression may be the mechanism canceling growth-suppressing signaling
      of TGF-beta in MG63 cells.

PMID- 14633706
TI  - Genetic signatures of differentiation induced by 1alpha,25-dihydroxyvitamin D3 in
      human colon cancer cells.
AB  - Epidemiological and preclinical data indicate that vitamin D and its most active
      metabolite 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] have anticancer
      activity. Accordingly, clinical trials are under way using several
      nonhypercalcemic 1alpha,25(OH)(2)D(3) analogues against various neoplasms
      including colon cancer. 1alpha,25(OH)(2)D(3) induces proliferation arrest and
      epithelial differentiation of human SW480-ADH colon cancer cells. We examined the
      gene expression profiles associated with 1alpha,25(OH)(2)D(3) exposure using
      oligonucleotide microarrays. 1alpha,25(OH)(2)D(3) changed the expression levels
      of numerous previously unreported genes, including many involved in
      transcription, cell adhesion, DNA synthesis, apoptosis, redox status, and
      intracellular signaling. Most genes were up-regulated, and only a small fraction
      were down-regulated. Fourteen of 17 candidate genes studied were validated as
      1alpha,25(OH)(2)D(3) target genes by Northern and Western blotting or
      immunocytochemistry. They included c-JUN, JUNB, JUND, FREAC-1/FoxF1, ZNF-44/KOX7,
      plectin, filamin, keratin-13, G(0)S2, and the putative tumor suppressors NES-1
      and protease M. There was little overlap between genes regulated after short (4
      h) or long (48 h) exposure. Gene regulatory effects of 1alpha,25(OH)(2)D(3) in
      SW480-ADH cells differed from those in LS-174T cells, which lack E-cadherin and
      do not differentiate in response to 1alpha,25(OH)(2)D(3). Data from this study
      reveal that 1alpha,25(OH)(2)D(3) causes a profound change in gene expression
      profiles and provide a mechanistic basis to the ongoing clinical studies using
      nonhypercalcemic vitamin D(3) derivatives for colon cancer prevention and
      treatment.

PMID- 14633707
TI  - Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed
      by the Ras oncogene enhances radiation resistance.
AB  - Oncogenic forms of the small GTPase Ras increase the resistance of cells to
      killing by ionizing radiation (IR). Although not all of the signaling pathways
      for radioresistance are well defined, it is now clear that Ras-dependent
      signaling pathways involved in radioresistance include those mediated by
      phosphatidylinositol 3'-kinase (PI3-K) and Raf. Nevertheless, PI3-K and Raf
      together are not sufficient to reconstitute all of the resistance conferred by
      Ras, indicating that other effectors must also contribute. We show here that Ras
      driven autocrine signaling through the epidermal growth factor receptor (EGFR)
      also contributes to radioresistance in Ras-transformed cells. Conditioned media
      (CM) collected from RIE-1 rat intestinal epithelial cells expressing oncogenic
      Ras increased the survival of irradiated cells. Ras-CM contains elevated levels
      of the EGFR ligand transforming growth factor alpha (TGF-alpha). Both Ras-CM and
      TGF-alpha stimulated EGFR phosphorylation, and exogenous TGF-alpha mimicked the
      effects of Ras-CM to increase radioresistance. Blocking EGFR signaling with the
      EGFR/HER-2 kinase inhibitor (KI) GW572016 decreased the postradiation survival of
      irradiated Ras-transformed cells and normal cells but had no effect on the
      survival of unirradiated cells. Ras-CM and TGF-alpha also increase PI3-K activity
      downstream of the EGFR and increase postradiation survival, both of which are
      abrogated by GW572016. Thus, Ras utilizes autocrine signaling through EGFR to
      increase radioresistance, and the EGFR KI GW572016 acts as a radiosensitizer. The
      observation that Ras-transformed cells can be sensitized to killing by ionizing
      radiation with GW572016 demonstrates that EGFR KIs could potentially be used to
      radiosensitize tumors in which radioresistance is dependent on Ras-driven
      autocrine signaling through EGFR.

PMID- 14633708
TI  - Keratinocyte growth conditions modulate telomerase expression, senescence, and
      immortalization by human papillomavirus type 16 E6 and E7 oncogenes.
AB  - Keratinocytes undergo a finite number of divisions in culture before senescing.
      The high-risk human papillomavirus (HPV) E6 and E7 oncoproteins prevent
      keratinocyte senescence and extend life span by interacting with p53 and pRb,
      respectively, and also by transcriptionally activating the human telomerase
      reverse transcriptase (hTERT) gene, which encodes the catalytic subunit of
      telomerase. We correlated telomerase activity, which was measured by a highly
      sensitive and quantitative real-time quantitative-PCR-based telomeric repeat
      amplification protocol assay, with telomere length and the expression of hTERT,
      p16(INK4a), and HPV-16 E6 and E7 in keratinocytes grown under two culture
      conditions. Primary human foreskin keratinocytes (HFKs) cultured in keratinocyte
      serum-free medium on plastic senesced at approximately 13 population doublings
      (PDs). Senescence was accompanied by a dramatic increase in p16(INK4A) levels, a
      marked decrease in telomerase, and only a slight decrease in telomere length. In
      contrast, HFKs grown in F medium on 3T3 fibroblast feeders maintained elevated
      telomerase and lower levels of p16(INK4A) for 60 PDs before senescing
      approximately 81 PDs. E7 was shown to act synergistically with E6 to super induce
      telomerase expression in a feeder environment-dependent manner. Culture of both
      HFKs and HFK/16E6E7 cells in the feeder environment significantly increased the
      number of doublings that these cells could undergo without a significant
      reduction in telomere length. Finally, transfer of either HFKs or HFK/16E6E7
      cells from plastic to the feeder fibroblast culture system significantly induced
      telomerase activity. This induction in telomerase was fully reversible and
      largely attributable to the medium. Our results suggest that the influence of
      keratinocyte culture conditions on the expression of telomerase and p16(INK4A)
      and on telomere maintenance is responsible, at least partially, for the
      differences in proliferative capacity, senescence, and HPV-keratinocyte
      interactions seen in the two culture systems.

PMID- 14633709
TI  - Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen
      species, and transactivate the epidermal growth factor receptor in breast
      epithelial cells.
AB  - Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), are known mammary
      carcinogens in rodents and may be involved in human breast cancer. We have
      reported previously that BaP can mimic growth factor signaling and increase cell
      proliferation in primary human mammary epithelial cells and the human mammary
      epithelial cell line MCF-10A. BaP-quinones (BPQs) are important metabolites of
      BaP that have been associated with the production of reactive oxygen species.
      Using a model of epidermal growth factor (EGF) withdrawal in MCF-10A, we
      hypothesized that production of reactive oxygen species by BPQs could lead to the
      activation of the EGF receptor (EGFR). Here, we demonstrate through electron
      paramagnetic resonance spectroscopy and flow cytometry that 1,6-BPQ and 3,6-BPQ
      produce superoxide anion and hydrogen peroxide in MCF-10A cells. Furthermore, we
      show that BPQs increase EGFR, Akt, and extracellular signal-regulated kinase
      activity, leading to increased cell number in the absence of EGF. The BPQ-induced
      EGFR activity and associated cell proliferation were attenuated by the EGFR
      inhibitor AG1478, as well as by the antioxidant N-acetyl cysteine. Overexpression
      of catalase, but not Cu/Zn superoxide dismutase, reduced the extent of BPQ
      dependent increased cell number and EGFR pathway activation. Moreover, the direct
      treatment of MCF-10A cells with hydrogen peroxide enhanced EGFR, Akt, and
      extracellular-regulated kinase phosphorylation that could be similarly inhibited
      by AG1478, N-acetyl cysteine, and catalase. Taken together, these data indicate
      that BPQs, through the generation of hydrogen peroxide, activate the EGFR in MCF
      10A cells, leading to increased cell number under EGF-deficient conditions.

PMID- 14633710
TI  - Antitumor effects of a soluble insulin-like growth factor I receptor in human
      ovarian cancer cells: advantage of recombinant protein administration in vivo.
AB  - Antitumor effects of a soluble form dominant negative of the type I insulin-like
      growth factor receptor (IGF-IR) designated as 486/STOP were evaluated in CaOV-3
      human ovarian cancer cells by establishing stable transformants overexpressing
      486/STOP and by administration of 486/STOP recombinant protein. Expression of
      486/STOP was detected from total cell lysates, as well as conditioned media
      collected from stable transformants. In stable transformants, growth in monolayer
      was slightly retarded, and anchorage-independent growth in vitro and
      tumorigenicity in vivo were markedly inhibited. Addition of conditioned media
      from 486/STOP cells inhibited anchorage-independent growth of parental cells.
      Although tumorigenicity of parental cells in vivo was abrogated when they were
      cocultured in monolayer with 486/STOP cells over 48 h before injection to nude
      mice, coinjection of parental cells and 486/STOP cells without preculture was not
      successful. In contrast, administration of 486/STOP partially purified
      recombinant protein inhibited tumorigenicity of parental cells in vivo. Because
      486/STOP cells result in massive apoptosis in vivo within 48 h, usage of a
      recombinant protein has a great advantage to use its unique bystander effect in
      vivo for clinical application.

PMID- 14633711
TI  - Probasin promoter (ARR(2)PB)-driven, prostate-specific expression of the human
      sodium iodide symporter (h-NIS) for targeted radioiodine therapy of prostate
      cancer.
AB  - Prostate cancer is one of the most promising candidates for sodium iodide
      symporter (NIS)-mediated gene therapy. Adenovirus-mediated expression of NIS that
      is driven by prostate-specific promoters induces generous radioiodine
      accumulation in prostate cancer cells that may be used for therapy with (131)I.
      We have recently developed a replication-deficient adenovirus carrying the human
      NIS cDNA linked to a composite probasin promoter, ARR(2)PB, aiming toward
      specific expression of the human NIS gene (h-NIS) in prostate tissue for targeted
      radioactive iodide therapy of prostate cancer (Ad-ARR(2)PB/hNIS). The ability of
      Ad-ARR(2)PB/hNIS to cause NIS expression in tumor cells was characterized by
      iodide uptake assay and compared with Ad-CMV/hNIS in which the h-NIS expression
      is driven by the cytomegalovirus (CMV) promoter. Androgen-dependent prostate
      cancer cell lines (LNCaP) and non-prostate origin tumor cell lines (SNU449, MCF
      7, HCT116, OVCAR-3, and Panc-1) were infected with the viral constructs, and
      perchlorate-sensitive (125)I uptake and NIS protein expression were measured. Ad
      ARR(2)PB/hNIS-infected LNCaP cells showed androgen-dependent and perchlorate
      sensitive iodide uptake. Iodide accumulation in LNCaP cells infected with Ad
      ARR(2)PB/hNIS, followed by incubation with synthetic androgen, was 5.3-fold
      increased compared with those coincubated with perchlorate (15,184 +/- 1,173 cpm
      versus 2,837 +/- 187 cpm). Ad-ARR(2)PB/hNIS-infected LNCaP cells revealed a 3.2
      fold increase of iodide accumulation compared with those infected with Ad
      CMV/hNIS (multiplicity of infection = 30). Iodide uptake in a panel of non
      prostate tumor cell lines infected with Ad-ARR(2)PB/hNIS was no more than 2,500
      cpm, demonstrating the tissue specificity of this construct. These results
      indicate that Ad-ARR(2)PB/hNIS can be used to achieve high-magnitude and tissue
      specific expression of h-NIS in prostate tissue and is a promising candidate for
      cancer gene therapy of prostate cancer.

PMID- 14633712
TI  - Use of cyclooxygenase-2 inhibition to enhance the efficacy of immunotherapy.
AB  - Antitumor effects of cyclooxygenase-2 (COX-2) inhibition have been reported in a
      wide variety of tumor models and in human cancers, both as chemoprevention and
      therapy. Human mesothelioma tumors have been shown to overexpress COX-2 and high
      levels of COX-2 protein have been demonstrated to be a prognostic factor,
      indicating poor outcome in this tumor. In this study, we determined that
      inhibition of COX-2 by oral administration of Rofecoxib significantly slowed but
      did not cure the growth of small tumors in mesothelioma-bearing mice. Large
      tumors were unaffected. This effect was dependent on the presence of CD8+ T cells
      and was associated with increased tumor-infiltrating lymphocytes. Because these
      activities are consistent with a mechanism that results in a decrease in the
      immunosuppressive environment of the tumor, we additionally examined the effect
      of COX-2 blockade combined with Ad.IFN-beta therapy, a treatment that we have
      previously demonstrated results in expansion of antitumor CD8+ CTLs and cures a
      high percentage of small mesothelioma tumors in mice. Ad.IFN-beta therapy
      combined with COX-2 inhibition was associated with an increased number of T cells
      within tumors and resulted in cures of small tumors, significant inhibition of
      the growth of large established tumors, and inhibition of the growth of
      metastatic tumor foci after surgical debulking. The additive effects of these
      modes of treatment suggests that it would be rational to combine COX-2 inhibition
      with immuno- and immunogene therapy approaches (perhaps in conjunction with
      surgical debulking) in human clinical trials of treatment of mesothelioma and
      other tumors.

PMID- 14633713
TI  - Macrophages transduced with an adenoviral vector expressing interleukin 12
      suppress tumor growth and metastasis in a preclinical metastatic prostate cancer
      model.
AB  - We investigated the efficacy of intratumoral injection of macrophages transduced
      with murine IL-12 recombinant adenoviral vector (AdmIL-12) using the orthotopic
      178-2 BMA mouse prostate cancer model. AdmIL-12-transduced macrophages secreted
      IL-12 in vitro and demonstrated increased surface expression of MHC classes I and
      II as well as F4/80 antigen compared with uninfected macrophages or those
      infected with an adenoviral vector containing beta-galactosidase (Adbetagal) in
      control macrophages. AdmIL-12-transduced macrophages injected into orthotopic 178
      2 BMA tumors in vivo induced significant suppression of primary tumor growth and
      spontaneous lung metastases compared with controls. These antitumor and
      antimetastatic effects were comparable with those resulting from direct
      orthotopic delivery of the AdmIL-12 vector. Mice with orthotopic tumors treated
      with AdmIL-12-transduced macrophages survived significantly longer than controls.
      Analysis of tumors demonstrated significantly increased infiltration of CD4+ and
      CD8+ T cells in those injected with AdmIL-12-transduced macrophages compared with
      controls. Splenocyte-derived cytotoxic natural killer cell activity was enhanced
      on day 2 after AdmIL-12-transduced macrophage injection, and on day 14, tumor
      specific T-lymphocyte activities were increased compared with control, Adbetagal
      infected macrophages. Trafficking studies confirmed that intratumorally injected,
      AdmIL-12-transduced macrophages could migrate to draining lymph nodes. Overall,
      this novel approach to prostate cancer therapy demonstrates antitumor immune
      responses that provide effective antimetastatic activities in preclinical
      studies.

PMID- 14633714
TI  - Tumor suppression by a rationally designed reversible inhibitor of methionine
      aminopeptidase-2.
AB  - Methionine aminopeptidase (MetAP)-2 has been suggested as a novel target for
      cancer therapy because the anticancer agent TNP-470 irreversibly inactivates the
      catalytic activity of this enzyme. However, the importance of MetAP2 in cell
      growth and tumor progression was uncertain because previous data were based on
      the chemically reactive TNP-470. Here we show that a rationally designed
      reversible MetAP2 inhibitor, A-357300, suppresses tumor growth preclinically
      without the toxicities observed with TNP-470. We have synthesized this bestatin
      type MetAP2 inhibitor with the aid of crystal structures of the enzyme-inhibitor
      complexes and parallel synthesis. A-357300 induces cytostasis by cell cycle
      arrest at the G(1) phase selectively in endothelial cells and in a subset of
      tumor cells, but not in most primary cells of nonendothelial type. A-357300
      inhibits angiogenesis both in vitro and in vivo and shows potent antitumor
      efficacy in carcinoma, sarcoma, and neuroblastoma murine models. These data
      affirm that MetAP2 plays a pivotal role in cell growth and establish that
      reversible MetAP2 inhibitors are promising novel cancer therapeutic agents.

PMID- 14633715
TI  - Near-infrared optical imaging of epidermal growth factor receptor in breast
      cancer xenografts.
AB  - The specificity of a novel epidermal growth factor (EGF)-Cy5.5 fluorescent
      optical probe in the detection of EGF receptor (EGFr) was assessed using
      continuous-wave fluorescence imaging accomplished via an intensified charge
      coupled device (CCD) camera. Human mammary MDA-MB-468 (EGFr+) and MDA-MB-435
      (EGFr-) cancer cells were incubated with Cy5.5, EGF-Cy5.5, or the anti-EGFr
      monoclonal antibody C225 or EGF followed by EGF-Cy5.5 and examined under a
      fluorescence microscope. In vivo imaging was performed on mice with s.c. MDA-MB
      468 and MDA-MB-435 tumors. Images were obtained every 6 s for 20 min after i.v.
      injection of each agent and every 24 h after injection for up to 192 h.
      Additionally, mice with MDA-MB-468 tumors were injected i.v. with C225 24 h
      before injection of EGF-Cy5.5. EGF-Cy5.5, but not Cy5.5 or indocyanine green dye
      (ICG), bound to MDA-MB-468 cells. Binding of EGF-Cy5.5 was blocked by C225 and by
      EGF. In contrast, binding of EGF-Cy5.5 to MDA-MB-435 cells was not observed.
      Monitoring of the time-fluorescence intensity in mice confirmed that ICG and
      Cy5.5 had no favorable binding to tumor regardless of EGFr expression level. In
      contrast, EGF-Cy5.5 accumulated only in MDA-MB-468 tumors. Moreover, tumor uptake
      of EGF-Cy5.5 was blocked by C225. ICG and Cy5.5 fluorescence was completely
      absent from the tumor site, regardless of EGFr expression level, 24 h after
      injection. Little EGF-Cy5.5 fluorescence was detected in MDA-MB-435 tumors 24 h
      after injection. In MDA-MB-468 tumors, our data suggest that EGF-Cy5.5 may be
      used as a specific NIR contrast agent for noninvasive imaging of EGFr expression
      and monitoring of responses to molecularly targeted therapy.

PMID- 14633716
TI  - Free and N-(2-hydroxypropyl)methacrylamide copolymer-bound geldanamycin
      derivative induce different stress responses in A2780 human ovarian carcinoma
      cells.
AB  - The effects of geldanamycin (GA), 17-(3-aminopropylamino)-17
      demethoxygeldanamycin (AP-GA), and N-(2-hydroxypropyl)methacrylamide copolymer-AP
      GA conjugate [P(AP-GA)] on A2780 human ovarian carcinoma cells at an equitoxic
      dose (2x IC(50)) were compared by the gene expression array analysis. All
      treatments resulted in similar gene expression profiles up to 12 h (e.g., down
      regulation of CDK4 and up-regulation of APAF-1), although P(AP-GA)-treated cells
      showed delayed gene expression because of time-dependent internalization of the
      conjugate and intracellular drug release from P(AP-GA). However, AP-GA-treated
      cells showed elevated expression of HSP70 and HSP27 after 6 h compared with that
      observed by GA and P(AP-GA) treatments. Depletion of C-Raf, an HSP90 client
      protein, was observed in all treatments up to 12 h. Confocal microscopy using
      mesochlorin e(6) as a model drug revealed that drug release caused by the
      lysosomal cleavage of glycylphenylalanylleucylglycine oligopeptide spacer, used
      as GA derivative copolymer attachment/release point, was moderately fast. These
      results suggested that AP-GA treatment may activate stress-response pathways,
      whereas P(AP-GA) treatment may suppress them and trigger signaling pathways
      essential to cell growth arrest and death by inducing an HSP90-active factor.
      Although GA and P(AP-GA) treatments induced a time-dependent increase in HSP70
      and HSP27 protein expression (detected by Western blotting analysis), AP-GA
      treatment resulted in more rapid and more intense expression of both proteins.
      Our results suggest that conjugation of AP-GA to N-(2
      hydroxypropyl)methacrylamide copolymer may be able to modulate the cell stress
      responses induced by AP-GA because of differences in its internalization
      mechanism, subcellular localization, and intracellular concentration gradients.

PMID- 14633717
TI  - Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer
      progression in bone.
AB  - Prostate cancer (CaP) develops metastatic bone lesions that consist of a mixture
      of osteosclerosis and osteolysis. We have previously demonstrated that targeting
      receptor activator of nuclear factor kappaB ligand (RANKL) with osteoprotegerin
      (OPG) prevents the osteolytic activity of CaP and its ability to establish tumor
      in bone. However, OPG can block tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL)-mediated apoptosis, suggesting that the clinical use of OPG may
      prevent apoptosis of tumors mediated by TRAIL. Thus, methods to block RANKL
      activity, other than OPG, may be important. Accordingly, we evaluated the ability
      of soluble murine RANK-Fc (sRANK-Fc) to prevent progression of established CaP in
      a severe combined immunodeficient mouse implanted with fetal human bone. We first
      confirmed that sRANK did not block TRAIL-mediated apoptosis of LuCaP cells in
      vitro and that it did block LuCaP-conditioned media-induced osteoclastogenesis in
      vitro. Then, LuCaP 35 CaP cells were injected into the marrow space of the bone
      implanted in the severe combined immunodeficient mice implanted with fetal human
      bone and allowed to develop into tumors for 6 weeks. Either vehicle or sRANK-Fc
      was then administered for 6 weeks. sRANK-Fc diminished tumor-induced osteoblastic
      lesions as demonstrated by radiograph, bone mineral density measurement, and bone
      histomorphometry. sRANK-Fc also reduced systemic bone remodeling markers,
      including serum osteocalcin and bone-specific alkaline phosphatase and urine N
      telopeptide of collagen. Finally, sRANK-Fc decreased serum prostate-specific
      antigen levels and tumor volume in the bone, which indicates decreased tumor
      burden. In contrast, sRANK-Fc had no effect on s.c. implanted LuCaP cells. We
      conclude that sRANK-Fc is an effective inhibitor of RANKL that diminishes
      progression of CaP growth in bone through inhibition of bone remodeling.

PMID- 14633718
TI  - Gene expression and mitotic exit induced by microtubule-stabilizing drugs.
AB  - To explore the molecular mechanisms underlying the actions of Taxol and the
      functionally related molecule epothilone B (EpoB), we have analyzed the gene
      expression profiles in A549 cells in response to increasing concentrations of
      these microtubule-stabilizing drugs. An almost identical expression pattern was
      observed in cells treated with either Taxol or EpoB. Low concentrations of the
      drugs induced aberrant mitosis including asymmetric and multipolar cell
      divisions. At drug concentrations that triggered G(2)-M arrest, cells escaped
      from a prolonged mitotic arrest without cell division, resulting in tetraploid
      G(1) cells. This mitotic slippage is correlated with diminished expression of
      cdc2 kinase, topoisomerase IIalpha, BUB3, and BUB2-like protein 1, as well as
      with an increased expression of 14-3-3-sigma. Poly(ADP-ribose) polymerase
      cleavage, an early indicator of apoptosis, occurred in cells undergoing mitotic
      slippage and in aneuploid cells resulting from aberrant mitosis. In contrast,
      cells arrested in mitosis demonstrated no signal for apoptosis but had an
      increased expression of survivin, an inhibitor of apoptosis. Induction of
      aneuploid or tetraploid G(1) cells was accompanied by increased expression of
      CD95, p21, and BTG2 that may contribute to cell death because their expression
      was diminished in an EpoB-resistant cell line. In contrast, expression of GADD45
      and PTGF-beta could promote cell survival. We conclude that abnormal mitotic exit
      is required for apoptotic cell death induced by microtubule-stabilizing drugs.

PMID- 14633719
TI  - Genotypic and phenotypic comparisons of de novo and acquired melphalan resistance
      in an isogenic multiple myeloma cell line model.
AB  - Cancer cell adhesion confers a transient, de novo drug-resistant phenotype
      referred to as cell adhesion-mediated drug resistance (CAM-DR). In this report,
      we extend the CAM-DR phenotype to primary specimens from patients with myeloma,
      providing further evidence that CAM-DR is a viable clinical form of drug
      resistance. To examine mechanisms of cellular resistance to melphalan, we
      compared genotypic and phenotypic profiles of acquired and de novo melphalan
      resistance in an isogenic human myeloma cell line. Acquired melphalan resistance
      (8226/LR5) was associated with decreased drug-induced DNA damage and a complex
      gene expression profile showing that genes involved in the Fanconi anemia DNA
      repair pathway are increased in the LR5 cells compared with drug-sensitive or
      adherent cells. In contrast, cells adhered to fibronectin accumulate similar
      amounts of DNA damage compared with drug-sensitive cells but are protected from
      melphalan-induced mitochondrial perturbations and caspase activation. Levels of
      the proapoptotic protein Bim were significantly reduced in adherent cells. Gene
      expression changes associated with de novo resistance were significantly less
      complex compared with acquired resistance, but a significant overlap in gene
      expression was noted involving cholesterol synthesis. We propose that myeloma
      cell adhesion promotes a form of de novo drug resistance by protecting cells from
      melphalan-induced cytotoxic damage and that this transient protection allows
      cells to acquire a more permanent and complex drug resistance phenotype
      associated with a reduction in drug induced DNA damage.

PMID- 14633720
TI  - Differential EphA2 epitope display on normal versus malignant cells.
AB  - The EphA2 receptor tyrosine kinase is overexpressed in many different types of
      human cancers where it functions as a powerful oncoprotein. Dramatic changes in
      the subcellular localization and function of EphA2 have also been linked with
      cancer, and in particular, unstable cancer cell-cell contacts prevent EphA2 from
      stably binding its ligand on the surface of adjoining cells. This change is
      important in light of evidence that ligand binding causes EphA2 to transmit
      signals that negatively regulate tumor cell growth and invasiveness and also
      induce EphA2 degradation. On the basis of these properties, we have begun to
      target EphA2 on tumor cells using agonistic antibodies, which mimic the
      consequences of ligand binding. In our present study, we show that a subset of
      agonistic EphA2 antibodies selectively bind epitopes on malignant cells, which
      are not available on nontransformed epithelial cells. We also show that such
      epitopes arise from differential cell-cell adhesions and that the stable
      intercellular junctions of nontransformed epithelial cells occlude the binding
      site for ligand, as well as this subset of EphA2 antibodies. Finally, we
      demonstrate that antibody targeting of EphA2 decreases tumor cell growth as
      measured using xenograft tumor models and found that the mechanism of antibody
      action relates to EphA2 protein degradation in vivo. Taken together, these
      results suggest new opportunities for therapeutic targeting of the large number
      of different cancers that express EphA2 in a manner that could minimize potential
      toxicities to normal cells.

PMID- 14633721
TI  - Antagonists of growth hormone-releasing hormone inhibit the proliferation of
      experimental non-small cell lung carcinoma.
AB  - Recent studies show that antagonists of growth hormone-releasing hormone (GH-RH)
      inhibit proliferation of various cancers indirectly through blockage of the
      endocrine GH-insulin-like growth factor (IGF) I axis and directly by an action on
      tumor cells involving the suppression of autocrine/paracrine IGF-I, IGF-II, or GH
      RH. The effectiveness of therapy with GH-RH antagonist JV-1-38 and its mechanisms
      of action were investigated in NCI-H838 non-small cell lung carcinoma (NSCLC)
      xenografted s.c. into nude mice and in vitro. Treatment with GH-RH antagonist JV
      1-38 significantly (P < 0.05-0.001) inhibited tumor growth as demonstrated by a
      58% decrease in final tumor volume, 54% reduction in tumor weight, and the
      extension of tumor-doubling time from 8.5 +/- 1.38 to 12 +/- 1.07 days as
      compared with controls. Using ligand competition assays with (125)I-labeled GH-RH
      antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on
      tumor membranes. Reverse transcription-PCR revealed the expression of mRNA for GH
      RH and splice variant 1 (SV(1)) of GH-RH receptor in H838 tumors. Reverse
      transcription-PCR analysis also demonstrated that H838 tumors express IGF-I and
      IGF-I receptors. Tumoral concentration of IGF-I and its mRNA expression were
      significantly decreased by 25% (P = 0.05) and 65% (P < 0.001), respectively, in
      animals receiving JV-1-38, whereas serum IGF-I levels remained unchanged. In
      vitro studies showed that H838 cells secreted GH-RH and IGF-I into the medium.
      The growth of tumor cells in vitro was stimulated by IGF-I and inhibited by GH-RH
      antagonist JV-1-38 and a GH-RH antiserum. Our results extend the findings on the
      involvement of IGF-I in NSCLC and suggest that GH-RH may be an autocrine growth
      factor for H838 NSCLC. The antitumorigenic action of GH-RH antagonists could be
      partly direct and mediated by SV(1) of tumoral GH-RH receptors. The finding of GH
      RH and SV(1) of GH-RH receptors in NSCLC provides a new approach to the treatment
      of this malignancy based on the use of antagonistic analogues of GH-RH.

PMID- 14633722
TI  - Deoxyribonucleic acid (DNA) encoding a pan-major histocompatibility complex class
      II peptide analogue augmented antigen-specific cellular immunity and suppressive
      effects on tumor growth elicited by DNA vaccine immunotherapy.
AB  - Vaccine immunotherapy must induce helper and cytotoxic cell-mediated immunity to
      generate the powerful antitumor immune responses needed to suppress cancer
      progression. We reported previously that a 16-amino acid peptide analogue derived
      from pigeon cytochrome c can bind broad ranges of MHC class II types and activate
      helper T cells in mice. To determine whether DNA encoding the Pan-MHC class II IA
      peptide (Pan-IA) can increase the efficacy of tumor suppression by DNA vaccine
      immunotherapy targeting tumor antigens, Pan-IA DNA was administered with
      ovalbumin (OVA) DNA to C57BL/6 mice bearing the OVA-expressing tumor cell line
      E.G7. Specific proliferative responses to and cytotoxic activities against OVA
      expressing targets were induced in mice vaccinated with both OVA and Pan-IA DNA
      but not in those vaccinated with OVA DNA alone or control DNA plus Pan-IA DNA.
      Growth of E.G7 cells was suppressed only by combined vaccination with OVA and Pan
      IA DNA, and tumors in five of the nine mice that received this combined
      vaccination were eradicated completely. In those mice, the frequency of CD8
      positive T cells reactive with OVA(257-264) peptides in the context of H-2K(b)
      was significantly increased in the tumor site. Furthermore, immunofluorescent
      study of the inoculated tumors revealed increased accumulation of both CD4- and
      CD8-positive T cells producing IFN-gamma in the tumor only by this vaccine
      protocol. The data suggest that Pan-IA DNA can augment suppressive effects of DNA
      vaccines on tumor growth by increasing numbers of antigen-specific CTLs and
      helper T cells. This is the first study in which established tumors have been
      eradicated successfully by vaccination with DNA corresponding to CTL epitopes and
      helper T cell epitopes. Our animal model may contribute to the development of
      therapeutic DNA vaccines against cancer.

PMID- 14633723
TI  - Both hepatocyte growth factor (HGF) and stromal-derived factor-1 regulate the
      metastatic behavior of human rhabdomyosarcoma cells, but only HGF enhances their
      resistance to radiochemotherapy.
AB  - Rhabdomyosarcomas (RMSs) are frequently characterized by bone marrow involvement.
      Recently, we reported that human RMS cells express the CXC chemokine receptor-4
      (CXCR4) and postulated a role for the CXCR4 stromal-derived factor (SDF)-1 axis
      in the metastasis of RMS cells to bone marrow. Because RMS cells also express the
      tyrosine kinase receptor c-MET, the specific ligand hepatocyte growth factor
      (HGF) that is secreted in bone marrow and lymph node stroma, we hypothesized that
      the c-MET-HGF axis modulates the metastatic behavior of RMS cells as well.
      Supporting this concept is our observation that conditioned media harvested from
      expanded ex vivo human bone marrow fibroblasts chemoattracted RMS cells in an HGF
      and SDF-1-dependent manner. Six human alveolar and three embryonal RMS cell
      lines were examined. We found that although HGF, similar to SDF-1, did not affect
      the proliferation of RMS cells, it induced in several of them: (a) locomotion;
      (b) stress fiber formation; (c) chemotaxis; (d) adhesion to human umbilical vein
      endothelial cells; (e) trans-Matrigel invasion and matrix metalloproteinase
      secretion; and (f) phosphorylation of mitogen-activated protein kinase p42/44 and
      AKT. Moreover HGF, but not SDF-1, increased the survival of RMS cells exposed to
      radio- and chemotherapy. We also found that the more aggressive alveolar RMS
      cells express higher levels of c-MET than embryonal RMS cell lines and
      "home/seed" better into bone marrow after i.v. injection into immunocompromised
      mice. Because we could not find any activating mutations in the kinase region of
      c-MET or any evidence for HGF autocrine stimulation, we suggest that the
      increased response of RMS cell lines depends on overexpression of functional c
      MET. We conclude that HGF regulates the metastatic behavior of c-MET-positive RMS
      cells, directing them to the bone marrow and lymph nodes. Signaling from the c
      MET receptor may also contribute to the resistance of RMS cells to conventional
      treatment modalities.

PMID- 14633724
TI  - Replication of an adenoviral vector controlled by the human telomerase reverse
      transcriptase promoter causes tumor-selective tumor lysis.
AB  - Telomerase reactivation is a critical step for tumorigenesis, allowing cancer
      cells to proliferate indefinitely. Taking advantage of this property, we
      generated an adenovirus vector in which E1 gene expression, and therefore viral
      replication, is under control of the human telomerase reverse transcriptase
      (hTERT) promoter. This vector, referred to as Ad5-hTERT-E1, replicated in cancer
      cells and demonstrated efficient cancer-selective cytolysis in a variety of tumor
      cell lines, including HT-1080 (fibrosarcoma cells); HeLa (cervical carcinoma
      cells); A549 (lung carcinoma cells); Hep G2 (hepatocellular carcinoma cells); SCC
      4, SCC-25, and SCCLSU-1 (head and neck squamous cell carcinoma cells); T24
      (bladder carcinoma); and DU 145 (prostate carcinoma). In contrast, the identical
      multiplicities of infection of Ad5-hTERT-E1 had no effect on primary cultures of
      normal human fibroblasts, airway epithelial cells, and bone marrow mesenchymal
      stem cells. Moreover, a single injection of Ad5-hTERT-E1 into preexisting HT-1080
      solid tumors, established s.c. in nu/nu mice, efficiently suppressed tumor
      growth. Interestingly, this conditionally replicating vector transactivated the
      replication of an E1-deleted antitumor adenoviral vector, Ad5-RSV-hsvTK, in tumor
      cells, demonstrating a synergistic antitumor effect in vivo. Combinational
      injection of a single dose of Ad5-hTERT-E1 and Ad5-RSV-hsvTK vector resulted in
      significant tumor suppression and regression after ganciclovir treatment. These
      results suggest that the Ad5-hTERT-E1 vector has potential as a broad-spectrum
      antitumor agent.

PMID- 14633725
TI  - Modified vaccinia virus ankara recombinants are as potent as vaccinia
      recombinants in diversified prime and boost vaccine regimens to elicit
      therapeutic antitumor responses.
AB  - Cancer vaccine regimens use various strategies to enhance immune responses to
      specific tumor-associated antigens (TAAs), including the increasing use of
      recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA
      to the immune system. However, the use of replication competent vectors with the
      potential of adverse reactions have made attenuation a priority for next
      generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication
      defective form of vaccinia virus. Here, we investigated the use of MVA encoding a
      tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple
      costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte
      function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA
      CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA
      CEA/TRICOM could be administered twice in vaccinia naive mice and only a single
      time in vaccinia-immune mice before being inhibited by antivector-immune
      responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine
      regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both
      CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM
      prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA
      CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant
      therapeutic antitumor response as measured by increased survival, when compared
      with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The
      studies reported here demonstrate that MVA, when used as a prime in a diversified
      vaccination, is clearly comparable with the regimen using the recombinant
      vaccinia in both the induction of cellular immune responses specific for the
      "self"-TAA transgene and in antitumor activity.

PMID- 14633726
TI  - Arsenic trioxide inhibits translation of mRNA of bcr-abl, resulting in
      attenuation of Bcr-Abl levels and apoptosis of human leukemia cells.
AB  - Present studies demonstrate that treatment with arsenic trioxide (AT) lowered
      ectopically expressed or endogenous levels of Bcr-Abl protein, as well as induced
      apoptosis of Bcr-Abl-expressing cultured and primary chronic myeloid leukemia
      cells, including those refractory to imatinib mesylate. Treatment with AT neither
      affected bcr-abl mRNA transcript levels nor promoted the proteasomal degradation
      of Bcr-Abl. Importantly, in [(35)S]methionine-labeled leukemia cells, exposure to
      AT rapidly lowered the levels of the newly synthesized Bcr-Abl, indicating
      inhibition of bcr-abl mRNA translation. Treatment with AT rapidly inhibited the
      activity of 3-phosphoinositide-dependent protein kinase-1, as well as of p70 S6
      kinase-1. p70 S6 kinase-1 is known to be a positive regulator of the translation
      of a group of mRNAs that possesses a long and highly structured 5'-untranslated
      region (UTR) containing a tract of oligopyrimidines (TOP). Because bcr-abl mRNA
      was discovered to possess a long and highly structured 5'-UTR containing a 12
      pyrimidine TOP sequence in its 5'-UTR, we determined the effect of AT in Jurkat
      cells with ectopic expression of a 5'-UTR-deleted mutant of the bcr-abl gene,
      i.e., Jurkat/Bcr-Abl (5'UTR-) cells. Treatment with AT neither lowered the levels
      of the 5'-UTR-deleted mutant of Bcr-Abl nor induced apoptosis of Jurkat/Bcr-Abl
      (5'UTR-) cells. Taken together, these findings demonstrate a novel mechanism by
      which AT down-regulates Bcr-Abl levels and induces apoptosis of Bcr-Abl-positive
      chronic myelogenous leukemia cells.

PMID- 14633727
TI  - Rac1 and Rac3 are targets for geranylgeranyltransferase I inhibitor-mediated
      inhibition of signaling, transformation, and membrane ruffling.
AB  - Rac1, a Rho family GTPase, is a mediator of diverse cellular functions including
      membrane ruffling, cell cycle progression, and transformation. Rac3, a close
      relative of Rac1, is less well characterized. Posttranslational addition of
      geranylgeranyl isoprenoid lipids to Rac proteins is required for biological
      activity. Inhibitors of geranylgeranyl transferase I (GGTIs) are currently under
      investigation as a possible anticancer therapy, although the targets of GGTIs
      have not been determined. We created COOH-terminal mutants of Rac1 and Rac3 that
      are farnesylated and used them to characterize Rac1 and Rac3 as physiological
      targets of GGTIs. We show that, like Rac1, activated Rac3 causes transformation
      and leads to membrane ruffling. Farnesylated versions of Rac1 and Rac3 retain the
      ability to signal to the transcription factor c-Jun and cause membrane ruffling
      and transformation, indicating that switching isoprenoid modification does not
      alter function. Finally, treatment with GGTIs led to the inhibition of membrane
      ruffling and transforming activities of both activated and wild-type Rac1 and
      Rac3. However, the farnesylated versions of both activated and wild-type Rac1 and
      Rac3 were resistant to the inhibitory effects of GGTIs. These results illustrate
      that Rac1 and Rac3 are potential physiological targets for these novel drugs.

PMID- 14633728
TI  - RNA-directed actions of 8-chloro-adenosine in multiple myeloma cells.
AB  - The purine analogue, 8-chloro-adenosine (8-Cl-Ado), induces apoptosis in a number
      of multiple myeloma (MM) cell lines. This ribonucleoside analogue accumulates as
      a triphosphate and selectively inhibits RNA synthesis without perturbing DNA
      synthesis. Cellular RNA is synthesized by one of three polymerases (Pol I, II, or
      III); thus, the inhibition of one or more RNA polymerases may be mediating 8-Cl
      Ado cytotoxicity. Here, we have addressed this question by dissecting the RNA
      directed actions of 8-Cl-Ado in MM cells. Differential alterations in
      [(3)H]uridine incorporation were found in the three major classes of RNA after a
      20-h exposure with 10 microM 8-Cl-Ado. The synthesis rate of Pol III transcripts,
      5 S and tRNA, remained unchanged, whereas Pol I-mediated rRNA synthesis decreased
      by approximately 20%. In contrast, mRNA synthesis, which is transcribed by Pol
      II, rapidly declined within 4 h and reached a 50% decrease, which was maintained
      for 20 h. Parallel to RNA synthesis inhibition, 8-Cl-Ado was maximally
      incorporated in the mRNA (>13 nmol/mg RNA), which was 5-fold higher than the tRNA
      and rRNA incorporation. Electrophoretic and radiographic analysis of newly
      synthesized and processed [(14)C]uridine-labeled transcripts indicated that the
      analogue blocks transcription elongation. Consistent with that result, high
      performance liquid chromatography analysis of micrococcal nuclease and spleen
      phosphodiesterase-digested RNA demonstrated that the analogue incorporation is at
      the 3' terminus. In conclusion, our data demonstrate that in MM cells, 8-Cl-Ado
      is preferentially incorporated into mRNA, suggesting a propensity toward Pol II,
      and inhibits RNA synthesis by premature transcriptional chain termination.

PMID- 14633729
TI  - Potent inhibitor of N-myristoylation: a novel molecular target for cancer.
AB  - N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the
      cotranslational and/or posttranslational transfer of myristate to the NH(2)
      terminus of the glycine residue of a number of important proteins that have
      diverse biological functions and thus have been proposed as potential targets for
      chemotherapeutic drug design. Earlier, we demonstrated that NMT is more active in
      colonic epithelial neoplasms than in corresponding normal-appearing colonic
      tissue. Furthermore, an increased expression of NMT was also observed in
      gallbladder carcinoma. In the present study, we report a novel protein inhibitor
      of NMT. This protein caused a potent concentration-dependent inhibition of human
      NMT with half-maximal inhibition at 4.5 +/- 0.35 nM. This study will serve as a
      template for further investigations in the area of protein myristoylation.

PMID- 14633730
TI  - The cytoplasmic domain is critical to the tumor suppressor activity of TSLC1 in
      non-small cell lung cancer.
AB  - The tumor suppressor gene in lung cancer (TSLC1) encodes a membrane glycoprotein
      containing extensive homology in the extracellular domain with the immunoglobulin
      superfamily cell adhesion molecules. The intracellular cytoplasmic domain (CT)
      contains a protein 4.1 (FERM) binding motif, and a PDZ-interacting motif.
      Expression of TSLC1 is silenced in non-small cell lung cancer and in other
      cancers by promoter hypermethylation. Restoration of TSLC1 expression suppresses
      tumorigenicity of lung cancer cells. We report here the critical role of the FERM
      binding and PDZ- interacting domains of TSLC1 in tumor suppressor activity in non
      small cell lung cancer. The entire CT domain [amino acid (aa) 398-442], the FERM
      binding motif (aa 398-410), or the PDZ-interacting motif (aa 432-442) was deleted
      to generate mutants CT1, CT3, and CT4, respectively. The lung cancer cell line
      A549, deficient in TSLC1 expression, was stably transfected with the wild-type
      TSLC1 or the deletion mutants. The cell lines were then injected into athymic
      (nu/nu) nude mice, and tumor formation at the sites of injection was monitored.
      A549 cells stably transfected with the empty vector or mutant TSLC1 constructs
      induced tumors at the sites of injection within 10 days. In contrast, A549 cells
      expressing wild-type TSLC1 showed the appearance of tumors after 35 days, and the
      tumors grew substantially slower. A549 cells expressing wild-type TSLC1 also
      showed suppression of anchorage-independent colony formation in soft agar and
      markedly increased cell-cell adhesion activity. These results suggest that the
      cytoplasmic domain of TSLC1 is important in its tumor suppressor activity, and
      the tumor suppression activity involve protein(s) interacting with the FERM- and
      PDZ-interacting regions.

PMID- 14633731
TI  - In vitro tests of the validity of singlet oxygen luminescence measurements as a
      dose metric in photodynamic therapy.
AB  - Singlet oxygen ((1)O(2)) is widely believed to be the major cytotoxic agent
      involved in photodynamic therapy (PDT). We showed recently that measurement of
      the weak near infrared luminescence of (1)O(2) is possible in cells in vitro and
      tissues in vivo. Here, we investigated the relationship between the integrated
      luminescence signal and the in vitro PDT response of AML5 leukemia cells
      sensitized with aminolevulinic acid-induced protoporphyrin IX (PpIX). Sensitized
      cell suspensions were irradiated with pulsed 523 nm laser light at average
      fluence rates of 10, 25, or 50 mWcm(-2) and, (1)O(2) luminescence measurements
      were made throughout the treatment. Cell survival was measured with either
      propidium iodide-labeled flow cytometry or colony-forming assay. The PpIX
      concentration in the cells, the photobleaching, and the pO(2) in the cell
      suspensions were also monitored. There were large variations in cell survival and
      (1)O(2) generation in different experiments due to different controlled treatment
      parameters (fluence and fluence rate) and other uncontrolled factors (PpIX
      synthesis and oxygenation). However, in all of the cases, cell kill correlated
      strongly with the cumulative (1)O(2) luminescence and allowed direct estimation
      of the (1)O(2) per cell required to achieve a specific level of cell kill. This
      study supports the validity and potential utility of (1)O(2) luminescence
      measurement as a dosimetric tool for PDT, as well as confirming the likely role
      of (1)O(2) in porphyrin-based PDT.

PMID- 14633732
TI  - Natural IgM antibodies and immunosurveillance mechanisms against epithelial
      cancer cells in humans.
AB  - Malignancy is like a chronic disease, and the immune system is permanently
      involved in recognizing and eliminating the transformed cells. The human
      hybridoma technology offers the unique opportunity to study the mechanisms,
      structures, and targets involved in recognition and elimination of aberrant
      cells. Thousands of tumor-reactive human monoclonal antibodies were isolated by
      this technique from cancer patients and from healthy donors, and all of these
      antibodies were IgM antibodies; no IgG and IgA antibodies were found. Fourteen of
      these antibodies were selected for DNA sequence analysis, characterization of
      their binding patterns, and determination of their origin and genetics. All of
      the IgM antibodies studied expressed only few or no mutations at all (germ-line
      coded), bound to carbohydrates on modified tumor-specific receptors and induced
      apoptosis. The degree of cross-reactivity to other tumors correlated reciprocally
      with the number of mutations in coding regions. By using an anti-idiotypic
      antibody we were able to show that the IgM-producing cells were of CD5+ B-cell
      origin. The data presented here indicate that the innate immunity and natural IgM
      antibodies play an important role in immunosurveillance mechanisms against
      epithelial tumors in humans.

PMID- 14633733
TI  - Retinoids act as multistep modulators of the major histocompatibility class I
      presentation pathway and sensitize neuroblastomas to cytotoxic lymphocytes.
AB  - The current therapeutic modalities achieve low response rates in human
      neuroblastoma, a frequent extracranial malignancy of the early childhood. We have
      assessed the effect of retinoids, used presently for the treatment of
      neuroblastoma, on the discrete steps of the MHC class I processing machinery and
      susceptibility of neuroblastoma cells to CTL-mediated killing. We demonstrate
      that retinoic acid derivatives induce the expression of proteolytic and
      regulatory subunits of the immunoproteasome, increase the half-life of MHC class
      I complexes, and enhance the sensitivity of neuroblastoma cells to both MHC class
      I-restricted peptide-specific and HLA nonrestricted lysis by CTLs. Importantly,
      effects of retinoids on the MHC class I pathway appear to be independent of IFN
      gamma and/or TNF-alpha as intermediate messengers. To our knowledge, this is the
      first demonstration of inflammation-unrelated biological molecules that induce
      systemic modulation of antigen presentation in nonprofessional antigen presenting
      cells. Our findings suggest that the application of retinoids and T cell-based
      immunotherapy may be an effective combination for the treatment of neuroblastoma.

PMID- 14633734
TI  - Antitumor activity mediated by double-negative T cells.
AB  - Allogeneic lymphocytes are potent mediators of leukemia and lymphoma remission.
      The goal of this study was to determine whether single MHC class I locus
      mismatched lymphocytes could generate an antilymphoma activity in the absence of
      graft-versus-host-disease (GVHD) and to understand the underlying mechanisms.
      Immunoincompetent Scid or lethally irradiated mice were challenged i.v. with a
      lethal dose of A20 lymphoma cells together with an infusion of single MHC class I
      locus mismatched splenocytes. Mice that were challenged with A20 cells alone
      succumbed to lymphoma between 34 and 50 days after infusion. In contrast, >75% of
      mice that were coinfused with single class I MHC locus mismatched splenocytes
      survived indefinitely (n = 20) in the absence of GVHD. Interestingly, the number
      of CD3(+)CD4(-)CD8(-) double-negative (DN) T cells increased 15-fold in mice that
      did not develop lymphoma. Both DN T cells isolated from the spleens of lymphoma
      free mice and DN T cells cloned from naive mice were cytotoxic to A20 lymphoma
      cells in vitro. When DN T cell clones were infused into naive mice i.v. together
      with A20 lymphoma cells, 86% of recipient mice were protected from lymphoma onset
      and did not develop GVHD (n = 22). To assess whether the systemic injection of DN
      T cells can also suppress local tumor development, A20 cells were infused i.m.,
      and at the same time DN T cell clones were infused either i.v. or i.m. Results
      indicated that DN T cells infused systemically (i.v.) could not prevent local
      tumor outgrowth, but DN T cells coinfused locally (i.m.) prevented local tumor
      development in 91% of animals (n = 11). Furthermore, we demonstrate that primary
      DN T cells were also able to prevent tumor growth in 75% of mice when infused
      together with A20 cells i.m. (n = 12). Together, these results demonstrate that
      an antilymphoma activity can be generated in mice without causing GVHD.
      Furthermore, DN T cells can suppress lymphoma cells in vivo and in vitro,
      suggesting that DN T cells could be used as a novel strategy for the treatment of
      lymphoma.

PMID- 14633735
TI  - Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid
      neoplasia and hypercalcemic hyperparathyroidism.
AB  - The inactivation of the MEN1 tumor suppressor gene in patients leads to a
      constellation of changes in endocrine tissues, including parathyroid neoplasia,
      pituitary adenomas, pancreatic neuroendocrine tumors, and carcinoids. To study
      the pathophysiological consequences of the deletion of the MEN1 gene, we set out
      to create a mouse model of hyperparathyroidism resulting from the deletion of the
      Men1 gene in parathyroid tissue. We introduced a Men1 gene flanked by loxP sites
      into the mouse germ line and then used a parathyroid cell-specific promoter to
      drive the expression of Cre recombinase, resulting in the deletion of the Men1
      gene. Here, we show that loss of Men1 gene function in the parathyroid glands of
      mice results in histological changes consistent with parathyroid neoplasia as
      well as systemic hypercalcemia. This model provides a means for dissecting the
      molecular basis of this familial cancer syndrome and may allow for the
      development of new strategies to treat related forms of hypercalcemia.

PMID- 14633736
TI  - Pharmacological uncoupling of androgen receptor-mediated prostate cancer cell
      proliferation and prostate-specific antigen secretion.
AB  - The androgen receptor (AR), a member of the nuclear receptor family, is a ligand
      inducible transcription factor. In the prostate gland, androgens regulate the
      transcription of several genes that ultimately result in cell growth and
      differentiation. With a goal of developing tissue-selective AR modulators that
      can be used to treat prostate cancer and other androgenopathies, we have taken an
      approach to identify androgens that function in a manner distinct from the
      physiological androgens testosterone and dihydrotestosterone. Classical AR
      agonists function by binding to and inducing a conformational change in the
      receptor. This facilitates the obligate interaction of the amino and carboxyl
      terminus of the receptor, recruitment of coactivators, and subsequent regulation
      of target genes. On the basis of this paradigm, we screened a library of
      potential AR agonists for compounds that induce an "activating" conformational
      change in the receptor structure but that do not facilitate a high-affinity
      intermolecular interaction between the amino and carboxyl terminus. Compounds
      identified in this manner behaved as partial agonists of AR-mediated
      transcription in a variety of assays. Additional compounds were identified in
      this screen that did not allow the activation function-2 coactivator pocket to
      form and were demonstrated to function as weak agonists of AR-mediated
      transcription. Surprisingly, when we examined the ability of these compounds to
      induce cell proliferation, we observed that despite having different degrees of
      partial agonist activities on classical transcriptional responses (i.e.,
      induction of prostate-specific antigen), these compounds were as efficacious as
      dihydrotestosterone in stimulating proliferation. The unexpected finding that AR
      mediated transcription and proliferation can be uncoupled suggests that AR is not
      used in the same manner in all androgen-regulated biological processes.

PMID- 14633737
TI  - Signaling pathways of apoptosis activated by aromatase inhibitors and
      antiestrogens.
AB  - Aromatase inhibitors have recently been reported to be more effective than the
      antiestrogen tamoxifen (Tam) in treating breast cancer. Here, we studied the
      mechanisms and signaling pathways of cell growth, cell cycle progression, and
      apoptosis induced by three aromatase inhibitors: letrozole (Let), anastrozole,
      and 4-hydroxyandrostenedione in comparison with estrogen withdrawal (E2W) and
      antiestrogens Tam and faslodex. Estrogen-dependent human breast cancer cells
      stably transfected with aromatase (MCF-7Ca) were used. All treatments induced
      growth suppression and cell cycle arrest at the G(0)-G(1) phase that was
      associated with up-regulation of p53 and p21 protein and mRNA levels and down
      regulation of cyclin D1 and c-myc mRNA. The apoptotic index was increased 4-7
      fold, Bcl-2 protein expression decreased, Bax increased, and caspase-9, caspase
      6, and caspase-7 were activated but not caspase-3 and caspase-8. Let and E2W
      caused regression of tumors of MCF-7Ca cells grown in nude mice and increased the
      number of cells undergoing apoptosis. In contrast, Tam and faslodex did not
      induce tumor regression and a lower number of apoptotic cells was detected.
      Cleavage of poly(ADP-ribose) polymerase was detected. Treatment with Let, Tam, or
      E2W resulted in a dose- and time-dependent increase in active caspase-7 and up
      regulation of p53 and p21 protein. Although the mechanisms involved appeared to
      be similar for antiestrogens and aromatase inhibitors, the most significant
      effects occurred with Let, which were significantly greater than with E2W and
      consistent with marked effects of Let on tumor and cell growth.

PMID- 14633738
TI  - Interleukin-6 -174G-->C polymorphism is associated with improved outcome in high
      risk breast cancer.
AB  - Axillary lymph node involvement in breast cancer is a marker of recurrence risk.
      Despite aggressive adjuvant therapy, recurrence in patients with four or more
      involved lymph nodes approaches 50% at 5 years from diagnosis. Markers that can
      distinguish those likely to relapse from those likely to be cured are needed to
      tailor therapy and provide accurate prognostic information to patients. Although
      most work in this area has focused on tumor characteristics, we hypothesized that
      the host environment might also play a role in determining risk of relapse. We
      hypothesized that host inflammatory response, mediated in part by production of
      interleukin-6 (IL-6), might play a role in the elimination of microscopic
      residual tumor. Polymorphisms in the IL-6 promoter region appear to modulate
      serum levels of the cytokine via regulation of gene transcription. A single
      nucleotide polymorphism involving substitution of cytosine for guanine at
      position -174 has been associated with reduced transcription and improved outcome
      in a variety of nonmalignant diseases, including coronary artery disease and
      several autoimmune conditions. Tumor necrosis factor (TNF) alpha is a
      proinflammatory cytokine that also plays a role in regulating IL-6 transcription.
      We hypothesized that polymorphisms in IL-6 (-174 G>C) or TNF-alpha (G-238 or G
      308) might be associated with prognosis in a subset of patients with high-risk
      breast cancer. Genotyping was performed on DNA from stored stem cells in 80
      breast cancer patients diagnosed with at least four positive axillary lymph nodes
      at diagnosis who underwent anthracycline-based adjuvant chemotherapy followed by
      high-dose multiagent chemotherapy with stem cell rescue. Cox proportional hazards
      models were used to estimate the effect of genotype and other known prognostic
      factors on disease-free and overall survival (DFS and OS, respectively). The
      presence of at least one C allele in the IL-6 promoter at position -174 was
      significantly associated with both DFS and OS compared with G/G homozygotes.
      After adjustment for estrogen receptor (ER) status, number of involved lymph
      nodes, and tumor size, those patients carrying the G/G genotype had a 2.1-fold
      increase in the rate of failure and a 2.6-fold increase in the rate of death
      compared with carriers of any C allele at a mean follow-up of 55 months. ER
      status modulated the effect of IL-6 polymorphism: both DFS and OS were most
      favorable in patients who were carriers of any C-allele (G/C or C/C) and had ER
      positive tumors. The presence of either G/G genotype or an ER-negative tumor
      increased the hazard of failure [hazard ratio (HR), 2.6 and 3.2, respectively]
      and death (HR, 2.0 and 2.2, respectively). The combination of both G/G genotype
      and ER-negative tumor resulted in an additional increase in the hazard of failure
      (HR, 5.4; four-group comparison, P = 0.003) and death (HR, 6.2; four-group
      comparison, P = 0.001). TNF-alpha -308 and -238 polymorphisms were not associated
      with variation in DFS or OS in this cohort. The IL-6-174 promoter polymorphism is
      associated with clinical outcome in this cohort of node-positive breast cancer
      patients who received high-dose adjuvant therapy. IL-6 genotype modulated the
      effect of ER status on outcome. These results support the hypothesis that IL-6
      may play an important role in the control of micrometastatic disease in breast
      cancer. Additional studies are needed to confirm these results and elucidate the
      mechanisms responsible for these differences.

PMID- 14633739
TI  - Substantial reduction in risk of lung adenocarcinoma associated with genetic
      polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic
      activation of tobacco-specific carcinogen NNK.
AB  - Cytochrome P450 2A13 (CYP2A13), an enzyme expressed predominantly in the human
      respiratory tract, exhibits high efficiency in the metabolic activation of
      tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A C-->T
      transition in the CYP2A13 gene causes Arg257Cys amino acid substitution and,
      thus, results in a significantly reduced activity toward NNK and other
      substrates. In this case-control study, we genotyped 724 patients with lung
      cancer and 791 controls for this polymorphism to examine the hypothesis that the
      variant CYP2A13 may have impact on risk of lung cancer in relation to tobacco
      smoking. A gene deletion polymorphism (CYP2A6*4) in CYP2A6, another enzyme
      involved in the metabolic activation of tobacco nitrosamines, was also analyzed
      as a comparison. We found that, compared with the CC genotype, the variant
      CYP2A13 genotype (CT + TT) was associated with substantially reduced risk for
      lung adenocarcinoma [odds ratio (OR), 0.41; 95% confidence interval (CI), 0.23
      0.71], but not squamous cell carcinoma (OR, 0.86; 95% CI, 0.57-1.29) or other
      types of lung cancer (OR, 0.58; 95% CI, 0.32-1.09). Stratification analysis shows
      that the reduced risk of lung adenocarcinoma related to the variant CYP2A13
      genotype was limited to smokers, especially light smokers (OR, 0.23; 95% CI, 0.08
      0.68) but not nonsmokers or heavy smokers. No association was observed between
      CYP2A6 genotype and risk of lung cancer. Our results demonstrate for the first
      time that the variant CYP2A13 allele is associated with reduced risk of lung
      adenocarcinoma, suggesting the role of NNK-CYP2A13 interaction as a causative
      factor for the cancer.

PMID- 14633740
TI  - St. John's wort extracts and some of their constituents potently inhibit ultimate
      carcinogen formation from benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1.
AB  - Commercially available St. John's wort (Hypericum perforatum) preparations and
      some of their main constituents (hypericin, pseudohypericin, hyperforin, rutin,
      and quercetin) were examined for their potential to inhibit carcinogen activation
      by human cytochrome P450 1A1 (CYP1A1). We used a reconstituted system consisting
      of purified human CYP1A1, purified human NADPH-cytochrome P450 reductase, and
      dilaurylphosphatidylcholine as lipid component. St. John's wort extracts potently
      inhibited CYP1A1-catalyzed (+/-)-trans-7,8-dihydro-7,8-dihydroxy-benzo(a)pyrene
      (7,8-diol-B[a]P) epoxidation, the terminal reaction leading to the ultimate
      carcinogenic product (+/-)-B[a]P-r-7,t-8-dihydrodiol-t-9,10-epoxide (diolepoxide
      2). All constituents, except rutin, were shown to possess strong inhibitory
      potencies toward diolepoxide 2 formation from 7,8-diol-B[a]P, with IC(50) values
      of 0.5 microM (hypericin), 1.2 microM (hyperforin), 1.5 microM (quercetin), and 8
      microM (pseudohypericin), respectively. Preincubation experiments revealed that
      their action was not mechanism based. Inhibition kinetics studies showed the
      anthrodianthrone compound hypericin to be a noncompetitive inhibitor, with a K(i)
      value of 0.6 microM, and the phloroglucinol hyperforin to be a competitive
      inhibitor, with a K(i) value of 1.1 microM. When the effects on NADPH-P450
      reductase activity were investigated, all constituents of St. John's wort studied
      turned out to be rather ineffective inhibitors; quercetin was the only exception,
      with an IC(50) value of approximately 20 microM. These in vitro data indicate
      that St. John's wort extracts and some of their constituents potently inhibit the
      major human procarcinogen-activating enzyme CYP1A1.

PMID- 14633741
TI  - Meeting report on the Ninth Conference on Cancer Therapy with Antibodies and
      Immunoconjugates.
AB  - This conference, held biennially for the past 12 years, provides a forum where
      investigators from throughout the world can gather and discuss how monoclonal
      antibodies can be used to improve the treatment of cancer. As in the past, this
      meeting focused primarily on the use of radiolabeled antibodies in cancer
      treatment, but this year there were many additional contributions on the use of
      unconjugated "naked" antibodies for the treatment of cancer, reflecting a growing
      understanding that antibodies not only can be used to direct isotopes and drugs
      to tumors but can also be effective agents in themselves. Preclinical studies
      using immunoconjugates prepared with toxins, drugs, or other agents were also
      reported to be highly effective therapeutic agents. Some of these are now showing
      efficacy in clinical trials. In addition, presentations focused on a variety of
      approaches, including pretargeting, regional delivery, and combinations with
      other standard treatment regimens designed to optimize antibody-targeted
      treatment strategies. Although the most efficacious treatments were reported in a
      variety of hematological malignancies, there were a number of presentations,
      primarily in early preclinical development, that provided evidence for potential
      future improvements in the treatment of solid tumors.

PMID- 14633742
TI  - How low can we go?

PMID- 14633743
TI  - Bispectral index, serum drug concentrations and emergence associated with
      individually adjusted target-controlled infusions of remifentanil and propofol
      for laparoscopic surgery.
AB  - BACKGROUND: Target-controlled infusions (TCI) are used to simplify administration
      and increase precision of i.v. drugs during general anaesthesia. However, there
      is a limited relationship between preset targets and measured concentrations of
      drugs and between measured concentrations and measures of brain function, such as
      the bispectral index (BIS). METHODS: We set out to evaluate the performance of
      TCI devices for propofol (Diprifusor) and remifentanil (Remifusor, prototype),
      during laparoscopic cholecystectomy in 21 patients. We also checked if there was
      any correlation between serum concentrations of propofol and BIS during
      individually adjusted anaesthesia. RESULTS: The Diprifusor and Remifusor had a
      median absolute performance error of 60% and 25% respectively. Propofol
      concentrations were underpredicted by a median of 60%, and remifentanil
      concentrations were slightly overpredicted by a median of 7%. When anaesthesia
      was adjusted to keep BIS values between 45 and 60, no correlation existed between
      measured concentrations of propofol and the corresponding BIS values, although
      both BIS and serum propofol concentration discriminated well between the awake
      and asleep states. Emergence was rapid and uneventful in all patients. Female
      patients had a more rapid emergence than male patients (6.6 and 11.6 min
      respectively). CONCLUSIONS: TCI devices for remifentanil and propofol result in
      large variation in measured serum concentrations. The lack of correlation between
      BIS and serum concentrations of propofol adds to the debate about whether BIS
      measures hypnosis as a graded state during surgery. This study confirms that
      women wake up faster than men, but provides no explanation for this repeatedly
      shown difference.

PMID- 14633744
TI  - Effects of propofol on cerebral oxygenation and metabolism after head injury.
AB  - BACKGROUND: Flow-metabolism coupling is thought to be deranged after traumatic
      brain injury, while the effects of propofol on flow-metabolism coupling are
      controversial. We have used a step increase in target plasma propofol
      concentration in head injured patients to explore flow-metabolism coupling in
      these patients. METHODS: Ten patients with a moderate to severe head injury
      received a step increase in propofol target controlled infusion of 2 microg x ml(
      1). Cerebral tissue gas measurements were recorded using a multimodal sensor, and
      regional chemistry was assessed using microdialysis. Arterial-jugular venous
      oxygen differences (AVDO(2)) were measured and all patients had cortical function
      monitoring (EEG). RESULTS: The step increase in propofol led to a large increase
      in EEG burst-suppression ratio (0% (range 0-1.1) to 46.1% (range 0-61.7),
      P<0.05); however, this did not significantly change tissue gas levels, tissue
      chemistry, or AVDO(2). CONCLUSIONS: Flow-metabolism coupling remains intact
      during a step increase in propofol after traumatic brain injury. The EEG burst
      suppression induced by propofol after traumatic brain injury does not appear to
      be a useful therapeutic tool in reducing the level of regional ischaemic burden.

PMID- 14633745
TI  - Isocapnic hyperpnoea accelerates recovery from isoflurane anaesthesia.
AB  - BACKGROUND: Hyperventilation should speed up elimination of volatile anaesthetic
      agents from the body, but hyperventilation usually results in hypocapnia. We
      compared recovery from isoflurane anaesthesia in patients allowed to recover with
      assisted spontaneous ventilation (control) and those treated with isocapnic
      hyperpnoea. METHODS: Fourteen patients were studied after approximately 1 h of
      anaesthesia with isoflurane. Control patients were allowed to recover in the
      routine way. Isocapnic hyperpnoea patients received 2-3 times their
      intraoperative ventilation using a system to maintain end tidal PCO(2) at 45-50
      mm Hg. We measured time to removal of the airway and rate of change of bispectral
      index (BIS) during recovery. RESULTS: With isocapnic hyperpnoea, the time to
      removal of the airway was markedly less (median and interquartile range values of
      3.6 (2.7-3.7) vs 12.1 (6.8-17.2) min, P<0.001); mean (SD) BIS slopes during
      recovery were 11.8 (4.4) vs 4.3 (2.7) min(-1) (P<0.01) for isocapnic hyperpnoea
      and control groups, respectively. Isocapnic hyperpnoea was easily applied in the
      operating room. CONCLUSIONS: Isocapnic hyperpnoea at the end of surgery results
      in shorter and less variable time to removal of the airway after anaesthesia with
      isoflurane and nitrous oxide.

PMID- 14633746
TI  - Increased carbon dioxide absorption during retroperitoneal laparoscopy.
AB  - BACKGROUND: Retroperitoneoscopy for renal surgery is now a common procedure. We
      compared carbon dioxide absorption in patients undergoing retroperitoneoscopy for
      adrenal or renal surgery with that of patients undergoing laparoscopic
      cholecystectomy. METHODS: We measured carbon dioxide elimination with a metabolic
      monitor in 30 anaesthetized patients with controlled ventilation, undergoing
      retroperitoneoscopy (n=10), laparoscopy (n=10) or orthopaedic surgery (n=10).
      RESULTS: Carbon dioxide production increased by 38, 46 and 63% at 30, 60 and 90
      min after insufflation (P<0.01) in patients having retroperitoneoscopy. Carbon
      dioxide production (mean (SD)) increased from 92 (21) to 150 (43) ml x min(-1) m(
      2) 60-90 min after insufflation and remained increased after the end of
      insufflation. During laparoscopy, V(.)(CO(2)) increased less (by 15%) (P<0.05
      compared with retroperitoneoscopy) and remained steady throughout the procedure.
      CONCLUSION: Retroperitoneal carbon dioxide insufflation causes more carbon
      dioxide absorption than intraperitoneal insufflation, and controlled ventilation
      should be increased if hypercapnia should be avoided.

PMID- 14633747
TI  - Real-time breath monitoring of propofol and its volatile metabolites during
      surgery using a novel mass spectrometric technique: a feasibility study.
AB  - BACKGROUND: At present, there is no rapid method for determining the plasma
      concentration of i.v. anaesthetics. A solution might be the measurement of the
      anaesthetic concentration in expired breath and its relation to the plasma
      concentration. We used chemical ionization methods to determine whether an i.v.
      anaesthetic can be detected in the low concentrations (parts per billion by
      volume) in the expired breath of an anaesthetized patient. METHOD: Chemical
      ionization mass spectrometry can measure trace gases in air with high sensitivity
      without interference from major gases. We carried out a feasibility trial with a
      proton transfer reaction mass spectrometer (PTR-MS) to monitor the i.v.
      anaesthetic agent propofol and two of its metabolites in exhaled gas from an
      anaesthetic circuit. Exhaled gas was sampled via a 4 m long, unheated tube
      connected to the PTR-MS. RESULTS: Propofol and its metabolites were monitored in
      real time in the expired breath of patients undergoing surgery. CONCLUSION:
      Routine measurement of i.v. agents, analogous to that for volatile anaesthetic
      agents, may be possible.

PMID- 14633748
TI  - Fluoride metabolism in smokers and non-smokers following enflurane anaesthesia.
AB  - BACKGROUND: Inorganic fluoride is released by the metabolism of enflurane and the
      increased serum fluoride concentrations may impair renal function. Tobacco smoke
      consists of numerous reactive compounds that can either induce or inhibit drug
      metabolism. Studies on the interaction of smoking with anaesthetic drug
      metabolism and possible toxicity are warranted. METHODS: Sixteen non-smoking and
      17 smoking (>10 cigarettes day(-1)) generally healthy women undergoing elective
      gynaecological surgery were given 1 MAC (minimum alveolar concentration)-hour
      standardized anaesthesia with enflurane in oxygen-air mixture. The serum
      inorganic fluoride and renal function markers beta(2)-microglobulin, tumour
      associated trypsin inhibitor (TATI) and serum creatinine were measured for 48 h.
      RESULTS: The greatest inorganic fluoride concentration was between 8.4 and 21.0
      (mean 13.8 (SD 3.4)) micromol litre(-1) in the non-smokers and between 8.6 and
      38.0 (18.7 (7.0)) micromol litre(-1) in the smokers; the mean difference was 4.9
      micromol litre(-1) (95% confidence interval (CI) 1.0-8.8, P<0.05). Serum beta(2)
      microglobulin, TATI and creatinine were not increased. Serum inorganic fluoride
      concentrations were significantly greater in the smokers compared with the non-
      smokers 1, 2, 3 and 6 h after 1 MAC-hour inhalation with enflurane (P<0.05).
      Inorganic fluoride concentrations were still increased 24 h after anaesthesia in
      both groups. Urine beta(2)-microglobulin and TATI creatinine ratio remained at
      low values during the whole 48-h period in both groups. CONCLUSIONS: Regular
      smoking is associated with an increase in serum inorganic fluoride concentration
      after anaesthesia with enflurane, but there are no signs of renal damage.

PMID- 14633749
TI  - Low-dose remifentanil infusion does not impair natural killer cell function in
      healthy volunteers.
AB  - BACKGROUND: Mu opioid agonists suppress natural killer (NK) cell activity in
      animal models. Studies in human volunteers, however, have yielded conflicting
      results, with morphine suppressing and fentanyl increasing NK cell activity. This
      study evaluated the effect of a constant 8-h infusion of remifentanil on NK cell
      number and function in human volunteers. METHODS: After IRB approval and informed
      consent was obtained, 10 healthy volunteers underwent an 11 pm to 7 am infusion
      of saline, and at least 1 week later an infusion of 0.02-0.04 microg x kg(-1)
      min(-1) remifentanil. Blood was collected at 7 am for measurement of NK cell
      cytotoxicity using a (51)Cr release assay and measurement of NK cell number using
      fluorescent flow cytometry. RESULTS: Median and range of the total NK cell
      cytotoxicity (KU ml(-1)) was 745.0 (498.3-1483.6) on the control morning and
      818.6 (238.5-1454.5) on the morning following the remifentanil infusion. Neither
      the number of NK cells ml(-1) (2.5 x 10(5) (1.4 x 10(5)-4.2 x 10(5)) vs 2.7 x
      10(5) (1.1 x 10(5)-4.4 x 10(5))) nor the cytotoxicity per 1000 NK cells (KU 1000
      NK cells(-1)) (3.0 (1.8-5.2) vs 2.9 (0.9-6.7)) changed between the control and
      remifentanil conditions. CONCLUSIONS: An 8-h infusion of remifentanil did not
      affect NK cell activity in normal volunteers. This result differs from previous
      findings of morphine-induced NK cell activity suppression and fentanyl-induced NK
      cell activity enhancement in normal volunteers.

PMID- 14633750
TI  - Implicit memory formation in sedated ICU patients after cardiac surgery.
AB  - BACKGROUND: Recent research into memory formation under sedation has generated
      conflicting results. We investigated explicit and implicit memory in ICU patients
      during moderate to deep propofol sedation following cardiac surgery. METHODS: Two
      different methods of memory testing were used; (1). free-association (F-A) word
      pair testing (n=33) to test conceptual implicit memory and (2). process
      dissociation procedure (PDP) (n=26) to detect perceptual implicit and explicit
      memory. One hour after surgery, whilst sedated, the F-A group received one of two
      lists of 10 category-exemplar word-pairs through headphones, while the PDP group
      was presented with one of two lists of 16 five-letter words. When awake and co
      operative, the F-A group was tested using F-A testing, and the PDP group was
      tested using the PDP. RESULTS: The F-A group had a mean (SD) correct response
      rate of 7 (9)% for the target list, and 9 (8)% for the distractor list. The PDP
      group had a mean (SD) correct response rate of 11 (14) and 10 (13)% for the
      inclusion and exclusion lists, respectively, with mean correct response rates of
      13 (14)% for both the corresponding distractor lists. Neither group showed any
      significant differences between their responses and a list of distractor words
      (Wilcoxon tests). CONCLUSION: We found no evidence for memory formation in post
      cardiac surgery patients under moderate to deep propofol sedation.

PMID- 14633751
TI  - Constipation and its implications in the critically ill patient.
AB  - BACKGROUND: Motility of the lower gut has been little studied in intensive care
      patients. METHOD: We prospectively studied constipation in an intensive care unit
      of a university hospital, and conducted a national survey to assess the
      generalizability of our findings. RESULTS: Constipation occurred in 83% of the
      patients. More constipated patients (42.5%) failed to wean from mechanical
      ventilation than non-constipated patients (0%), P<0.05. The median length of stay
      in intensive care and the proportion of patients who failed to feed enterally
      were greater in constipated than non-constipated patients (10 vs 6.5 days and
      27.5 vs 12.5%, respectively (NS)). The survey found similar observations in other
      units. Delays in weaning from mechanical ventilation and enteral feeding were
      reported by 28 and 48% of the units surveyed, respectively. CONCLUSIONS:
      Constipation has implications for the critically ill.

PMID- 14633752
TI  - Study examining attitudes of staff, patients and relatives to witnessed
      resuscitation in adult intensive care units.
AB  - BACKGROUND: Witnessed resuscitation is widely accepted in paediatric practice and
      is becoming more common in adult emergency departments, but information on this
      topic is sparse. METHODS: We gave a questionnaire to 50 intensive care medical
      and nursing staff and 55 patients and next of kin before elective postoperative
      admission to the intensive care unit to examine staff opinion about witnessed
      resuscitation, patient and relatives' demand for witnessed resuscitation, and
      their perception of the benefits. RESULTS: We found that 56% of doctors and 66%
      of nurses favoured giving relatives the option to stay. If relatives requested to
      be present, 70% of doctors and 82% of nurses would allow this if the relatives
      were escorted. The role of the escort was felt to explain, prevent interference,
      and to provide emotional support. We found that 29% of patients and 47% of
      relatives wanted to be together during resuscitation, the commonest reasons being
      to provide support and to see that everything was done. We found that 95% of
      patients and 91% of relatives felt their views should be formally sought before
      ICU admission. CONCLUSIONS: Intensive care staff support witnessed resuscitation.
      Many intensive care personnel have experienced witnessed resuscitation and the
      majority felt that relatives gained benefit. Almost all agree that the views of
      both patient and relatives should be sought formally before admission to
      intensive care.

PMID- 14633753
TI  - Comparison of 1% and 2% lidocaine epidural anaesthesia combined with sevoflurane
      general anaesthesia utilizing a constant bispectral index.
AB  - BACKGROUND: The authors compared the effects of epidural anaesthesia with
      lidocaine 1% and lidocaine 2% on haemodynamic variables, sevoflurane
      requirements, and stress hormone responses during surgery under combined
      epidural/general anaesthesia with bispectral index score (BIS) kept within the
      range 40-50. METHODS: Thirty-three patients undergoing lower abdominal surgery
      were randomly divided into two groups to receive lidocaine 1% or 2% by epidural
      with sevoflurane general anaesthesia. Sevoflurane was adjusted to achieve a
      target BIS of 40-50 during maintenance of anaesthesia with nitrous oxide 60% in
      oxygen. Measurements included the inspired (FI(SEVO)) and the end-tidal
      sevoflurane concentrations (E'(SEVO)), blood pressure (BP), and heart rate (HR)
      before surgery and every 5 min during surgery for 2 h. Plasma samples were taken
      immediately before and during surgery for measurements of catecholamines,
      cortisol, and lidocaine. RESULTS: During surgery, both groups were similar for
      HR, BP and BIS, but FI(SEVO) and E'(SEVO) were significantly higher and more
      variable with lidocaine 1% than with 2%. Intraoperative plasma concentrations of
      epinephrine and cortisol were found to be higher with lidocaine 1% as compared
      with 2%. CONCLUSIONS: To maintain BIS of 40-50 during combined epidural/general
      anaesthesia for lower abdominal surgery, sevoflurane concentrations were lower
      and less variable with lidocaine 2% than with 1%. In addition, the larger
      concentration of lidocaine suppressed the stress hormone responses better.

PMID- 14633754
TI  - Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after
      joint replacement surgery.
AB  - BACKGROUND: As continuous wound instillation with local anaesthetic has not been
      evaluated after hip/knee arthroplasties, our study was designed to determine
      whether this technique could enhance analgesia and improve patient outcome after
      joint replacement surgery. METHODS: Thirty-seven patients undergoing elective
      hip/knee arthroplasties under spinal block were randomly assigned to two
      analgesia groups. Group M received continuous i.v. infusion of morphine plus
      ketorolac for 24 h. Then, a multi-hole 16 G catheter was placed subcutaneously
      and infusion of saline was maintained for 55 h. Group R received i.v. saline.
      Thereafter the wound was infiltrated with a solution of ropivacaine 0.5% 40 ml,
      then a multi-hole 16 G catheter was placed subcutaneously and an infusion of
      ropivacaine 0.2% 5 ml h(-1) was maintained for 55 h. Visual analogue scale scores
      were assessed at rest and on passive mobilization by nurses blinded to analgesic
      treatment. Total plasma ropivacaine concentration was measured. RESULTS: Group R
      showed a significant reduction in postoperative pain at rest and on mobilization,
      while rescue medication requirements were greater in Group M. Total ropivacaine
      plasma concentration remained below toxic concentrations and no adverse effects
      occurred. Length of hospital stay was shorter in Group R. CONCLUSION:
      Infiltration and wound instillation with ropivacaine 0.2% is more effective in
      controlling postoperative pain than systemic analgesia after major joint
      replacement surgery.

PMID- 14633755
TI  - Randomized prospective study of the analgesic effect of nefopam after orthopaedic
      surgery.
AB  - BACKGROUND: Balanced postoperative analgesia combines non-narcotic drugs and
      opioids. We organized a large study to evaluate nefopam analgesia and tolerance
      in combination with morphine for patient-controlled analgesia (PCA) after
      orthopaedic surgery. METHODS: Two hundred and one patients scheduled to undergo
      hip arthroplasty were included in this multicentre (n=24), double-blind,
      randomized study comparing nefopam (20 mg every 4 h for 24 h) with placebo, the
      first dose being infused peroperatively. The primary outcome measure was the
      cumulative morphine dose received postoperatively by PCA over 24 h. Secondary
      outcome measures were the amount of morphine received as a loading dose in the
      postanaesthesia care unit (PACU) and during the 24-h observation period, and pain
      assessments using a visual analogue scale (VAS) and a verbal pain scale (VPS),
      patient's satisfaction with analgesia and treatment tolerance. RESULTS: The two
      groups were comparable with respect to their characteristics and preoperative
      pain assessment. PCA-administered morphine over 24 h was significantly less for
      the nefopam group than the control group (21.2 (15.3) and 27.3 (19.2) mg
      respectively; P=0.02). This morphine-sparing effect was greater (35.1%) for
      patients with severe preoperative pain (VAS>30/100). For the entire study period
      (loading dose and PCA), morphine use was less for the nefopam group (34.5 (19.6)
      vs 42.7 (23.6) mg; P=0.01). Pain VAS at PACU arrival and during the whole PACU
      period was significantly lower for the nefopam than for the placebo group
      (P=0.002 and 0.04 respectively). Patient satisfaction was similar for the nefopam
      and placebo groups. CONCLUSION: In combination with PCA morphine, nefopam gives
      significant morphine-sparing with lower immediate postoperative pain scores
      without major side-effects. This analgesic effect seems to be particularly
      notable for patients with intense preoperative pain.

PMID- 14633756
TI  - Influence of peroperative opioid on postoperative pain after major abdominal
      surgery: sufentanil TCI versus remifentanil TCI. A randomized, controlled study.
AB  - BACKGROUND: Sufentanil and remifentanil are characterized by two different
      pharmacokinetic profiles. The aim of this study was to compare the effects of
      sufentanil and remifentanil administered using target-controlled infusion (TCI)
      on recovery and postoperative analgesia after major abdominal surgery. METHODS:
      Thirty adult patients scheduled for open colorectal surgery were included in a
      prospective, randomized study. Sufentanil TCI (sufentanil group) or remifentanil
      TCI (remifentanil group) was administered during surgery. In the remifentanil
      group, 30 min before the anticipated end of surgery, morphine 0.15 mg x kg(-1)
      was administered i.v. In the sufentanil group, an effect-site concentration of
      0.25 ng x ml(-1) was targeted at extubation. In both groups, postoperative pain
      was controlled by titration of i.v. morphine and then patient-controlled
      analgesia with morphine. RESULTS: The extubation time was similar in the two
      groups (mean (SD) 13 (6) and 14 (6) min in the sufentanil and remifentanil groups
      respectively). Visual analogue scale scores were significantly greater during the
      first 2 h after tracheal extubation in the remifentanil group than in the
      sufentanil group. The time to first analgesic request in the postanaesthesia care
      unit was significantly longer in the sufentanil group than in the remifentanil
      group (55 (64) (range 2-240) vs 11 (7) (1-29) min; P<0.001). The cumulative
      morphine dose for titration was significantly greater in the remifentanil group
      (P<0.01). The cumulative morphine dose used during titration and patient
      controlled analgesia was significantly greater in the remifentanil group 4, 12
      and 24 h after extubation (P<0.05). CONCLUSION: TCI sufentanil (0.25 ng ml(-1)
      effect-site concentration at extubation) is more effective than the
      intraoperative combination of remifentanil TCI infusion with morphine bolus (0.15
      mg x kg(-1)) for postoperative pain relief after major abdominal surgery and does
      not compromise extubation and recovery.

PMID- 14633757
TI  - Randomized, controlled, cross-over clinical trial comparing intravenous midazolam
      sedation with nitrous oxide sedation in children undergoing dental extractions.
AB  - BACKGROUND: The use of benzodiazepines for paediatric dental sedation has
      received limited attention with regard to research into clinical effectiveness. A
      study was therefore designed to investigate the use of midazolam, for i.v.
      sedation in paediatric dental patients. METHOD: The aim of the study was to
      assess the effectiveness of i.v. midazolam in a randomized, controlled, cross
      over trial. Children aged 12-16 yr (ASA I and II), requiring two appointments for
      equivalent but contralateral dental extractions for orthodontic purposes, were
      recruited. Conscious sedation with either i.v. midazolam titrated at 0.5 mg x
      min(-1), to a maximum of 5 mg, or nitrous oxide/oxygen titrated to 30%/70%
      inhalation sedation was used at the first visit, the alternative being used at
      the second visit. Vital signs including blood pressure, arterial oxygen
      saturation and ventilatory frequency, as well as sedation levels and behavioural
      scores, were recorded every 2 min. RESULTS: Forty patients, mean age 13.2 yr
      (range 12-16 yr), participated in the trial. A mean dose of midazolam 2.8 mg was
      administered in the test group. The median time to the maximum level of sedation
      was 8 min for midazolam compared with 6 min for nitrous oxide (P<0.001). Vital
      signs for both treatments were comparable and within acceptable clinical limits
      and communication with the patient was maintained at all times. The median
      (range) lowest arterial oxygen saturation level recorded for midazolam was 97 (91
      99)% compared with 97 (92-100)% for nitrous oxide. The mean (range) recovery time
      for midazolam was 51.6 (39-65) min and 23.3 (20-34) min for nitrous oxide
      (P<0.0001). Fifty-one per cent said they preferred i.v. midazolam, 38% preferred
      nitrous oxide, and 11% had no preference. CONCLUSION: I.V. midazolam sedation
      (0.5 mg x min(-1) to a maximum of 5 mg) appears to be as effective as nitrous
      oxide sedation in 12-16-yr-old healthy paediatric dental patients.

PMID- 14633758
TI  - Supplemental oxygen does not reduce postoperative nausea and vomiting after
      thyroidectomy.
AB  - BACKGROUND: Supplemental intra-operative oxygen 80% halves the incidence of
      nausea and vomiting after open and laparoscopic abdominal surgery, perhaps by
      ameliorating intestinal ischaemia associated with abdominal surgery. It is
      unlikely that thyroid surgery compromises intestinal perfusion. We therefore
      tested the hypothesis that supplemental perioperative oxygen does not reduce the
      risk of postoperative nausea and vomiting (PONV) after thyroidectomy. METHODS:
      One hundred and fifty patients undergoing thyroidectomy were given sevoflurane
      anaesthesia. After induction, patients were randomly assigned to the following
      treatments: (i). 30% oxygen, (ii). 80% oxygen, or (iii). 30% oxygen with
      droperidol 0.625 mg. RESULTS: The overall incidence of nausea during the first 24
      h after surgery was 48% in the patients given oxygen 30%, 46% in those given
      oxygen 80%, and 22% in those given droperidol (P=0.004). There were no
      significant differences between the oxygen 30% and 80% groups in incidence or
      severity of PONV, the need for rescue antiemetics, or patient satisfaction.
      Droperidol significantly shortened the time to first meal. CONCLUSIONS:
      Supplemental oxygen was ineffective in preventing nausea and vomiting after
      thyroidectomy, but droperidol reduced the incidence.

PMID- 14633759
TI  - Comparison of morphine-6-glucuronide and morphine on respiratory depressant and
      antinociceptive responses in wild type and mu-opioid receptor deficient mice.
AB  - BACKGROUND: Morphine-6-glucuronide (M6G) is a metabolite of morphine with potent
      analgesic properties. The influence of M6G on respiratory and antinociceptive
      responses was investigated in mice lacking the micro -opioid receptor (MOR) and
      compared with morphine. METHODS: Experiments were performed in mice lacking exon
      2 of the MOR (n=18) and their wild type (WT) littermates (n=20). The influence of
      M6G and morphine on respiration was measured using whole body plethysmography
      during three elevations of inspired carbon dioxide. Antinociception was assessed
      using tail flick and hotplate tests. RESULTS: In WT but not null mutant mice, a
      dose-dependent depression of the slope of the ventilatory carbon dioxide response
      was observed after M6G and morphine. Similarly, both opioids were devoid of
      antinociceptive effects in null mutant mice, but showed potent dose-dependent
      analgesia in WT animals. Potency differences between M6G and morphine in WT mice
      were of the same order of magnitude for analgesia and respiration. CONCLUSIONS:
      The data indicate that the desired (antinociceptive) and undesired (respiratory
      depression) effects of M6G and morphine are linked to the same gene product; that
      is the MOR. Other opioid- and non-opioid-receptor systems may play a minor role
      in the actions of M6Gs and morphine. The clinical implications of our findings
      are that any agent acting at the MOR will invariably cause (potent) analgesia in
      combination with (variable) respiratory depression.

PMID- 14633760
TI  - Comparison of isoflurane and propofol-fentanyl anaesthesia in a swine model of
      asphyxia.
AB  - BACKGROUND: There have been few studies comparing the response to asphyxia and
      the effectiveness of typical cardiopulmonary resuscitation (CPR) using exogenous
      epinephrine administration and manual closed-chest compression between total
      intravenous anaesthesia (TIVA) and inhalational anaesthesia. METHODS: Twenty pigs
      were randomly assigned to two study groups anaesthetized using either 2% end
      tidal isoflurane (n=10) or propofol (12 mg x kg(-1) h(-1))-fentanyl (50 microg x
      kg(-1)) (n=10). Asphyxia was induced by clamping the tracheal tube until the mean
      arterial pressure (MAP) decreased to 40% of the baseline value (40% MAP time).
      The tracheal tube was declamped at that point, and CPR was performed.
      Haemodynamic parameters and blood samples were obtained before the induction of
      asphyxia, at 1-min intervals during asphyxia, and 1, 2, 3, 5, 10, 30 and 60 min
      after asphyxia. RESULTS: TIVA maintained the MAP against hypoxia-hypercapnia
      stress significantly longer than isoflurane anaesthesia (mean (SD) 40% MAP time
      498 (95) and 378 (104) s respectively). In all animals in the isoflurane group,
      spontaneous circulation returned within 1 min of the start of CPR. In six of the
      TIVA animals, spontaneous circulation returned for 220 (121) s; spontaneous
      circulation did not return within 5 min in the remaining four animals.
      CONCLUSIONS: Although TIVA is less prone than isoflurane anaesthesia to primary
      cardiovascular depression leading to asphyxia, TIVA is associated with reduced
      effectiveness of CPR in which resuscitation because of asphyxic haemodynamic
      depression occurs.

PMID- 14633761
TI  - Dopexamine reverses colonic but not gastric mucosal perfusion defects in lethal
      endotoxin shock.
AB  - BACKGROUND: Whilst dopexamine appears to increase overall splanchnic blood flow
      in postoperative and septic patients, the effects on gastric mucosal perfusion
      are controversial and based on concomitantly increasing mucosal to arterial
      PCO(2) gradients (PdCO(2)). We hypothesized that dopexamine alters splanchnic
      blood flow distribution and metabolism during experimental endotoxin shock and
      modifies the inflammatory response induced by endotoxin. METHODS: In an
      experiment with anaesthetized normovolaemic, normoventilated pigs, 21 animals
      were randomized into: (i). subacute lethal endotoxin shock for 14 h (n=7 at
      baseline); (ii). endotoxin shock with dopexamine infusion (aiming to exceed
      baseline cardiac output, n=7); or (iii). controls (n=7). Regional blood flow and
      metabolism were monitored. RESULTS: Endotoxin produced a hypodynamic phase
      followed by a normo/hyperdynamic, hypotensive phase. Despite increasing systemic
      blood flow in response to dopexamine, proportional splanchnic blood flow
      decreased during the hypodynamic phase. Dopexamine gradually decreased fractional
      coeliac trunk flow, while fractional superior mesenteric arterial flow increased.
      Dopexamine induced early arterial hyperlactataemia and augmented the gastric
      PdCO(2) gradient while colonic luminal lactate release and colonic PdCO(2)
      gradient were reversed. Dopexamine did not modify the inflammatory response as
      evaluated by arterial IL-1beta and IL-6 concentrations. CONCLUSIONS: Dopexamine
      protects colonic, but not gastric mucosal epithelium in experimental endotoxin
      shock. This may be related to redistribution of blood flow within the splanchnic
      circulation.

PMID- 14633762
TI  - Anaesthesia for spinal surgery in adults.
AB  - The spectrum of spinal surgery in adult life is considerable. Anaesthesia for
      major spinal surgery, such as spinal stabilization following trauma or neoplastic
      disease, or for correction of scoliosis, presents a number of challenges. The
      type of patients who would have been declined surgery 20 yr ago for medical
      reasons, are now being offered extensive procedures. They commonly have
      preoperative co-morbid conditions such as serious cardiovascular and respiratory
      impairment. Airway management may be difficult. Surgery imposes further stresses
      of significant blood loss, prolonged anaesthesia, and problematical postoperative
      pain management. The perioperative management of these patients is discussed. The
      advent of techniques to monitor spinal cord function has reduced postoperative
      neurological morbidity in these patients. The anaesthetist has an important role
      in facilitating these methods of monitoring.

PMID- 14633763
TI  - Quality of perioperative AEP--variability of expert ratings.
AB  - BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be
      used to monitor anaesthetic depth. However, during surgery and anaesthesia, the
      quality of AEP recordings may be reduced by artefacts. This can affect the
      interpretation of the data and complicate the use of the method. We assessed
      differences in expert ratings of the signal quality of perioperatively recorded
      AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded
      perioperatively during a European multicentre study, was rated independently by
      five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality
      rating was calculated for each signal. Differences between quality ratings of the
      five experts were calculated for each AEP: inter-rater variability (IRV) was
      calculated as the difference between the worst and best classification of a
      signal. RESULTS: Average signal quality of 57% of the AEPs was rated as
      'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%,
      and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good,
      whereas a different expert thought the identical signal was invalid. CONCLUSIONS:
      There is poor agreement between experts regarding the signal quality of
      perioperatively recorded AEPs and, as a consequence, results obtained by one
      expert may not easily be reproduced by a different expert. This limits the use of
      visual AEP analysis to indicate anaesthetic depth and may affect the
      comparability of AEP studies, where waveforms were analysed by different experts.
      An objective automated method for AEP analysis could solve this problem.

PMID- 14633764
TI  - Metformin lactic acidosis, acute renal failure and rofecoxib.
AB  - A patient with acute renal failure associated with lactic acidosis as a result of
      concurrent treatment with metformin is described. Rofecoxib may have been a
      precipitating factor. The risk of renal failure with the use of traditional
      NSAIDs is well known. However, what is less well appreciated is the role that the
      COX 2 inhibitors may play in the development of renal failure which, when it
      occurs in a patient on metformin, can lead to a potentially disastrous outcome.

PMID- 14633765
TI  - Severe paradoxical intracranial embolism and pulmonary emboli during hip
      hemiarthroplasty.
AB  - Both paradoxical intracranial embolism, an intracranial arterial embolism caused
      by venous embolic material that has passed through a right-to-left shunt, and
      pulmonary arterial embolism are life-threatening complications of joint
      arthroplasty. We report a case of severe paradoxical intracranial embolism and
      pulmonary embolism that occurred during hip hemiarthroplasty.

PMID- 14633766
TI  - Non-invasive ventilation to avoid tracheal intubation in a patient with Guillain
      Barre syndrome.
AB  - A 72-yr-old man presented with respiratory failure secondary to Guillain-Barre
      syndrome. Although the criteria for mechanical ventilation were satisfied, the
      absence of weakness of the bulbar muscles allowed the safe use of non-invasive
      ventilation for 2 weeks in this patient. Invasive ventilation and tracheostomy
      were avoided and the patient made a good recovery.

PMID- 14633767
TI  - Anatomical variations of the phrenic nerve and its clinical implication for
      supraclavicular block.
AB  - This paper reports a case of simultaneous diaphragmatic and brachial plexus
      stimulation followed by a successful nerve block using the supraclavicular
      approach. An explanation for the qualitative differences in phrenic nerve block
      between interscalene and supraclavicular block is postulated, based on known
      anatomical variations.

PMID- 14633768
TI  - Inadvertent intrathecal injection of tramadol.
AB  - The present case report describes the observed sequelae following an inadvertent
      intrathecal injection of tramadol in a patient with metastatic malignancy. The
      contributing circumstances before the injection are discussed, as is the
      potential aetiology of the observed sequelae.

PMID- 14633769
TI  - Sub-Tenon's administration of local anaesthetic: a review of the technique.

PMID- 14633774
TI  - Ham-Wasserman lecture: treatment of acute leukemia by inducing differentiation
      and apoptosis.
AB  - Conventional treatment of acute leukemia involves the use of cytotoxic agents
      (chemotherapy), but other strategies have been explored. All-trans retinoic acid
      (ATRA) and arsenic have clearly been effective in the treatment of acute
      promyelocytic leukemia (APL), which creates the possibility that other types of
      acute leukemia can be conquered by selectively inducing differentiation and/or
      apoptosis. A great number of investigations have been performed to elucidate the
      mechanisms and search for effective agents in the treatment of other types of
      acute leukemia by these new strategies. Progress at the molecular level has been
      achieved in explaining the mechanisms of action of ATRA and arsenic compounds,
      and several new agents have emerged, although their clinical effectiveness
      remains to be confirmed. Mechanism-/gene-based targeted therapy and a combination
      of different strategies will improve the treatment of acute leukemia.

PMID- 14633775
TI  - Hemoglobinopathies.
AB  - The outlook for patients with sickle cell disease has improved steadily during
      the last two decades. In spite of these improvements, curative therapies are
      currently available only to a small minority of patients. The main theme of this
      chapter is to describe new therapeutic options that are at different stages of
      development that might result in further improvements in the outlook for patients
      with these disorders. Dr. Joseph DeSimone and his colleagues had previously made
      the important observation that the hypomethylating agent 5-azacytidine can
      reverse the switch from adult to fetal hemoglobin in adult baboons. Although
      similar activity was demonstrated in patients with sickle cell disease and beta
      thalassemia, concern about the toxicity of 5-azacytidine prevented its widespread
      use in these disorders. In Section I, Dr. DeSimone discusses the role of DNA
      methylation in globin gene regulation and describe recent clinical experience
      with decitabine (an analogue of 5-azacytidine) in patients with sickle cell
      disease. These encouraging studies demonstrate significant fetal hemoglobin
      inducing activity of decitabine in patients who fail to respond to hydroxyurea.
      In Section II, Dr. George Atweh continues the same theme by describing recent
      progress in the study of butyrate, another inducer of fetal hemoglobin, in
      patients with sickle cell disease and beta-thalassemia. The main focus of his
      section is on the use of a combination of butyrate and hydroxyurea to achieve
      higher levels of fetal hemoglobin that might be necessary for complete
      amelioration of the clinical manifestations of these disorders. Dr. Atweh also
      describes novel laboratory studies that shed new light on the mechanisms of fetal
      hemoglobin induction by butyrate. In Section III, Dr. Ronald Nagel discusses the
      different available transgenic sickle mice as experimental models for human
      sickle cell disease. These experimental models have already had a significant
      impact on our understanding of the pathophysiology of sickle cell disease. Dr.
      Nagel describes more recent studies in which transgenic sickle mice provide the
      first proof of principle that globin gene transfer into hematopoietic stem cells
      inhibits in vivo sickling and ameliorates the severity of the disease. Although
      stroke in adult patients with sickle cell disease is not as common as in
      children, adult hematologists, like their pediatric colleagues, need to make
      management decisions in adult patients with a stroke or a history of stroke. Dr.
      Robert Adams has led several large clinical studies that investigated the role of
      transfusions in the prevention of stroke in children with sickle cell disease.
      Much less is known, however, about the prevention of first or subsequent strokes
      in adult patients with sickle cell disease. In Section IV, Dr. Adams provides
      some general guidelines for the management of adult patients with stroke while
      carefully distinguishing between recommendations that are evidence-based and
      those that are anecdotal in nature.

PMID- 14633776
TI  - Iron deficiency and overload.
AB  - In the past seven years numerous genes that influence iron homeostasis have been
      discovered. Dr. Beutler provides a brief overview of these genes, genes that
      encode HFE, DMT-1, ferroportin, transferrin receptor 2, hephaestin, and hepcidin
      to lay the groundwork for a discussion of the various clinical forms of iron
      storage disease and how they differ from one another. In Section I, Dr. Beutler
      also discusses the types of hemochromatosis that exist as acquired and as
      hereditary forms. Acquired hemochromatosis occurs in patients with marrow
      failure, particularly when there is active ineffective erythropoiesis. Hereditary
      hemochromatosis is most commonly due to mutations in the HLA-linked HFE gene, and
      hemochromatosis clinically indistinguishable from HFE hemochromatosis is the
      consequence of mutations in three transferrin receptor-2 gene. A more severe,
      juvenile form of iron storage disease results from mutations of the gene encoding
      hepcidin or of a not-yet-identified gene on chromosome 1q. Autosomal dominant
      iron storage disease is a consequence of ferroportin mutations, and a
      polymorphism in the ferroportin gene appears to be involved in the African iron
      overload syndrome. Evidence regarding the biochemical and clinical penetrance of
      hemochromatosis due to mutations of the HFE gene is rapidly accumulating. These
      studies, emanating from several centers in Europe and the United States, all
      agree that the penetrance of hemochromatosis is much lower than had previously
      been thought. Probably only 1% of homozygotes develop clinical findings. The
      implications of these new findings for the management of hemochromatosis will be
      discussed. In Section II, Dr. Victor Hoffbrand discusses the management of iron
      storage disease by chelation therapy, treatment that is usually reserved for
      patients with secondary hemochromatosis such as occurs in the thalassemias and in
      patients with transfusion requirements due to myelodysplasia and other marrow
      failure states. Tissue iron can be estimated by determining serum ferritin
      levels, measuring liver iron, and by measuring cardiac iron using the MRI-T2*
      technique. The standard form of chelation therapy is the slow intravenous or
      subcutaneous infusion of desferoxamine. An orally active bidentate iron chelator,
      deferiprone, is now licensed in 25 countries for treatment of patients with
      thalassemia major. Possibly because of the ability of this compound to cross
      membranes, it appears to have superior cardioprotective properties.
      Agranulocytosis is the most serious complication of deferiprone therapy and
      occurs in about 1% of treated patients. Deferiprone and desferoxamine can be
      given together or on alternating schedules. A new orally active chelating agent
      ICL 670 seems promising in early clinical studies. In Section III, Dr. James Cook
      discusses the most common disorder of iron homeostasis, iron deficiency. He will
      compare some of the standard methods for identifying iron deficiency, the
      hemoglobin level, transferrin saturation, and mean corpuscular hemoglobin and
      compare these with some of the newer methods that have been introduced,
      specifically the percentage of hypochromic erythrocytes and reticulocyte
      hemoglobin content. The measurement of storage iron is achieved by measuring
      serum ferritin levels. The soluble transferrin receptor is a truncated form of
      the cellular transferrin receptor and the possible value of this measurement in
      the diagnosis of iron deficiency will be discussed. Until recently iron dextran
      was the only parental iron preparation available in the US. Sodium ferric
      gluconate, which has been used extensively in Europe for many years, is now
      available in the United States. It seems to have a distinct advantage over iron
      dextran in that anaphylactic reactions are much less common with the latter
      preparation.

PMID- 14633777
TI  - Update on cobalamin, folate, and homocysteine.
AB  - Three topics affecting cobalamin, folate, and homocysteine that have generated
      interest, activity, and advances in recent years are discussed. These are: (I).
      the application of an expanded variety of tools to the diagnosis of cobalamin
      deficiency, and how these affect and are affected by our current understanding of
      deficiency; (II). the nature of the interaction between homocysteine and vascular
      disease, and how the relationship is affected by vitamins; and (III). the
      improved understanding of relevant genetic disorders and common genetic
      polymorphisms, and how these interact with environmental influences. The
      diagnostic approach to cobalamin deficiency now allows better diagnosis of
      difficult and atypical cases and more confident rejection of the diagnosis when
      deficiency does not exist. However, the process has also become a complex and
      sometimes vexing undertaking. Part of the difficulty derives from the lack of a
      diagnostic gold standard among the many available tests, part from the
      overwhelming numerical preponderance of patients with subclinical deficiency (in
      which isolated biochemical findings exist without clinical signs or symptoms)
      among the cobalamin deficiency states, and part from the decreased availability
      of reliable tests to identify the causes of a patient's cobalamin deficiency and
      thus a growing deemphasis of that important part of the diagnostic process. In
      Section I, Dr. Carmel discusses the tests, the diagnostic issues, and possible
      approaches to the clinical evaluation. It is suggested no single algorithm fits
      all cases, some of which require more biochemical proof than others, and that
      differentiating between subclinical and clinical deficiency, despite their
      overlap, may be a helpful and practical point of departure in the evaluation of
      patients encountered in clinical practice. The arguments for and against a
      suggested expansion of the cobalamin reference range are also weighed. The
      epidemiologic data suggest that homocysteine elevation is a risk factor for
      vascular and thrombotic disease. In Section II, Dr. Green notes that the
      interactions of metabolism and clinical risk are not well understood and a
      causative relationship remains unproven despite new reports that lowering
      homocysteine levels may reduce vascular complications. Genetic and acquired
      influences may interact in important ways that are still being sorted out. The
      use of vitamins, especially folate, often reduces homocysteine levels but also
      carries potential disadvantages and even risks. Folate fortification of the diet
      and supplement use have also markedly reduced the frequency of folate deficiency,
      and cobalamin deficiency is now the more common deficiency state, especially
      among the elderly. Although genetic disorders are rare, they illuminate important
      metabolic mechanisms and pose diagnostic challenges, especially when clinical
      presentation occurs later in life. In Section III, Drs. Rosenblatt and Watkins
      use selected disorders to illustrate the subject. Imerslund-Grasbeck syndrome, a
      hereditary disorder of cobalamin absorption at the ileal level, demonstrates
      genetic heterogeneity. Finnish patients show mutation of the gene for cubilin,
      the multiligand receptor for intrinsic factor. Surprisingly, Norwegian and other
      patients have been found recently to have mutations of the AMN (amnionless) gene,
      mutations that are lethal in mice at the embryonic stage. Two disorders of
      cobalamin metabolism, cblG and cblE, are now known to arise from mutations of the
      methionine synthase and methionine synthase reductase genes, respectively. These
      disorders feature megaloblastic anemia and neurologic manifestations. The folate
      disorder selected for illustration, methylenetetrahydrofolate reductase (MTHFR)
      deficiency, paradoxically causes neurological problems but no megaloblastic
      anemia. This rare deficiency is the most common inborn error of folate
      metabolism. It is distinct from the very common MTHFR gene polymorphisms,
      mutations that cause mild to moderate reductions in MTHFR activity but no direct
      clinical manifestations. The MTHFR polymTHFR polymorphisms, especially the 677C-
      >T mutation, may contribute to vascular and birth defect risks, while reducing
      the risk of certain malignancies, such as colon cancer. These polymorphisms and
      those of genes for other enzymes and proteins related to cobalamin, folate, and
      homocysteine metabolism may be important role players in frequent interactions
      between genes and the environment.

PMID- 14633778
TI  - Acute myeloid leukemia and acute promyelocytic leukemia.
AB  - The therapeutic approach to the patient with acute myeloid leukemia (AML)
      currently evolves toward new frontiers. This is particularly apparent from the
      entree of high-throughput diagnostic technologies and the identification of
      prognostic and therapeutic targets, the introduction of therapies in genetically
      defined subgroups of AML, as well as the influx of investigational approaches and
      novel drugs into the pipeline of clinical trials that target pathogenetic
      mechanisms of the disease. In Section I, Dr. Bob Lowenberg reviews current issues
      in the clinical practice of the management of adults with AML, including those of
      older age. Dr. Lowenberg describes upcoming possibilities for predicting
      prognosis in defined subsets by molecular markers and reviews experimental
      strategies to improve remission induction and postinduction treatment. In Section
      II, Dr. James Griffin reviews the mechanisms that lead to activation of tyrosine
      kinases by mutations in AML, the consequences of that activation for the cell,
      and the opportunities for targeted therapy and discusses some examples of
      developing novel drugs (tyrosine kinase inhibitors) and their effectiveness in
      AML (FLT3). In Section III, Dr. Martin Tallman describes the evaluation and
      management of patients with acute promyelocytic leukemia, a notable example of
      therapeutic progress in a molecularly defined entity of leukemia. Dr. Tallman
      focuses on the molecular genetics of APL, current curative treatment strategies
      and approaches for patients with relapsed and refractory disease. In addition,
      areas of controversy regarding treatment are addressed.

PMID- 14633779
TI  - Pediatric acute lymphoblastic leukemia.
AB  - The outcome for children with acute lymphoblastic leukemia (ALL) has improved
      dramatically with current therapy resulting in an event free survival exceeding
      75% for most patients. However significant challenges remain including developing
      better methods to predict which patients can be cured with less toxic treatment
      and which ones will benefit from augmented therapy. In addition, 25% of patients
      fail therapy and novel treatments that are focused on undermining specifically
      the leukemic process are needed urgently. In Section I, Dr. Carroll reviews
      current approaches to risk classification and proposes a system that incorporates
      well-established clinical parameters, genetic lesions of the blast as well as
      early response parameters. He then provides an overview of emerging technologies
      in genomics and proteomics and how they might lead to more rational, biologically
      based classification systems. In Section II, Drs. Mary Relling and Stella Davies
      describe emerging findings that relate to host features that influence outcome,
      the role of inherited germline variation. They highlight technical breakthroughs
      in assessing germline differences among patients. Polymorphisms of drug
      metabolizing genes have been shown to influence toxicity and the best example is
      the gene thiopurine methyltransferase (TPMT) a key enzyme in the metabolism of 6
      mercaptopurine. Polymorphisms are associated with decreased activity that is also
      associated with increased toxicity. The role of polymorphisms in other genes
      whose products play an important role in drug metabolism as well as cytokine
      genes are discussed. In Sections III and IV, Drs. James Downing and Cheryl
      Willman review their findings using gene expression profiling to classify ALL.
      Both authors outline challenges in applying this methodology to analysis of
      clinical samples. Dr. Willman describes her laboratory's examination of infant
      leukemia and precursor B-ALL where unsupervised approaches have led to the
      identification of inherent biologic groups not predicted by conventional
      morphologic, immunophenotypic and cytogenetic variables. Dr. Downing describes
      his results from a pediatric ALL expression database using over 327 diagnostic
      samples, with 80% of the dataset consisting of samples from patients treated on a
      single institutional protocol. Seven distinct leukemia subtypes were identified
      representing known leukemia subtypes including: BCR-ABL, E2A-PBX1, TEL-AML1,
      rearrangements in the MLL gene, hyperdiploid karyotype (i.e., > 50 chromosomes),
      and T-ALL as well as a new leukemia subtype. A subset of genes have been
      identified whose expression appears to be predictive of outcome but independent
      verification is needed before this type of analysis can be integrated into
      treatment assignment. Chemotherapeutic agents kill cancer cells by activating
      apoptosis, or programmed cell death. In Section V, Dr. John Reed describes major
      apoptotic pathways and the specific role of key proteins in this response. The
      expression level of some of these proteins, such as BCL2, BAX, and caspase 3, has
      been shown to be predictive of ultimate outcome in hematopoietic tumors. New
      therapeutic approaches that modulate the apoptotic pathway are now available and
      Dr. Reed highlights those that may be applicable to the treatment of childhood
      ALL.

PMID- 14633780
TI  - Chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) was the first human malignancy to be associated
      with a specific genetic lesion, the Philadelphia chromosome, harboring the BCR
      ABL oncogene. Since then, it has become a paradigm for the discovery of molecular
      mechanisms and targeted therapeutic approaches in the field of hematologic
      neoplasias. The past 5 years or so have been particularly fruitful in the
      dissection of the signal transduction pathways abnormally activated in CML and in
      the translation of this knowledge to clinical practice. In this report, we
      discuss the biological basis for such translation and highlight the current and
      potential tools for the effective treatment of CML patients. The first part
      presents a review of the basic concepts on the biology of CML and their
      application to the design of targeted therapy. The mechanisms of action of the
      molecular-specific drugs currently used in clinical trials are discussed, with
      emphasis on the description of the most promising new compounds that are
      enhancing the potential for effective alternative or combination chemotherapy in
      CML. In the following section, we explain how molecular monitoring of response to
      imatinib mesylate in patients with CML can be used as a guide to clinical
      management. In particular, we discuss the relative value of regular quantitative
      RT/PCR and cytogenetic analyses, how responding patients should be monitored and
      managed, and how to investigate patients who are refractory or become resistant
      to imatinib treatment. In the last part of this report, a discussion on the
      possibility of managing CML with patient-specific strategies is presented. We
      review the current treatment options, highlight the factors impacting on decision
      making, discuss the range of possibilities for future therapeutic strategies and
      propose a systematic approach for individualizing treatment for patients in
      different disease categories.

PMID- 14633781
TI  - Biology and treatment of chronic lymphocytic leukemia.
AB  - Major advances have occurred in our understanding of the biology, immunology, and
      opportunities for treatment of chronic lymphocytic leukemia (CLL) in recent
      times. Surface antigen analysis has helped us define classical CLL and
      differentiate it from variants such as marginal zone leukemia, mantle cell
      leukemia, and prolymphocytic leukemia. An important observation has been that the
      B-cells in indolent types of CLL, which do not require therapy, have undergone
      somatic hypermutation and function as memory B-lymphocytes whereas those more
      likely to progress have not undergone this process. Section I by Dr. Nicholas
      Chiorazzi encompasses emerging elements of the new biology of CLL and will
      address the types of somatic hypermutation that occur in CLL cells and their
      correlation with other parameters such as telomere length and ZAP70 status. In
      addition he addresses the concept of which cells are proliferating in CLL and how
      we can quantitate the proliferative thrust using novel methods. The interaction
      between these parameters is also explored. Section II by Dr. Thomas Kipps focuses
      on immune biology and immunotherapy of CLL and discusses new animal models in
      CLL, which can be exploited to increase understanding of the disease and create
      new opportunities for testing the interaction of the CLL cells with a variety of
      elements of the immune system. It is obvious that immunotherapy is emerging as a
      major therapeutic modality in chronic lymphocytic leukemia. Dr. Kipps addresses
      the present understanding of the immune status of CLL and the role of passive
      immunotherapy with monoclonal antibodies such as rituximab, alemtuzumab, and
      emerging new antibodies. In addition the interaction between the CLL cells and
      the immune system, which has been exploited in gene therapy with transfection of
      CLL cells by CD40 ligand, is discussed. In Section III, Dr. Michael Keating
      examines the question "Do we have the tools to cure CLL?" and focuses on the fact
      that we now have three distinct modalities, which are able to achieve high
      quality remissions with polymerase chain reaction (PCR) negativity for the
      immunoglobulin heavy chain in CLL. These modalities include initial
      chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, the use of
      alemtuzumab for marrow cytoreduction in minimal residual disease and allogeneic
      bone marrow transplants. The emergence of non-ablative marrow transplants in CLL
      has led to the broadening of the range of opportunities to treat older patients.
      The addition of rituximab to the chemotherapy preparative regimens appears to be
      a significant advance. The combination of our increased understanding of the
      biology, immune status, and therapy of CLL provides for the first time the
      opportunity for curative strategies.

PMID- 14633782
TI  - Myelodysplastic syndrome.
AB  - The last decade has witnessed a multistep evolution in the understanding of the
      natural history, clinical manifestations, and some of the molecular mechanisms
      that underlie the ineffective hematopoiesis and leukemic transformation in the
      myelodysplastic syndrome (MDS). The international prognostic scoring system, FAB,
      and WHO classifications have helped define specific subgroups with their
      characteristic cytogenetic, molecular and immunological abnormalities. Until
      recently the mainstay of the treatment has been entirely supportive with blood
      and platelet transfusions. What is increasingly manifest now is the considerable
      excitement generated by the emergence of novel therapeutic strategies based on
      painstaking research findings from the laboratories. In Section I, Dr. Alan List
      reviews the therapeutic strategies with the specific emphasis on the relevance of
      molecular mechanism of apoptosis and targeted therapies using small molecules. Of
      particular interest is the excitement surrounding the clinical benefit obtained
      from potent immunomodulatory derivative (IMiD) of thalidomide CC5013. The review
      provides an update of the role of small molecule inhibitors of VEGF receptor
      tyrosine kinase, arsenic trioxide, oral matrix metalloprotease inhibitors,
      farnesyl transferase inhibitors, and imatinib mesylate in the treatment of MDS
      subgroups. In Section II, Dr. Steven Gore describes the results of clinical
      trials of inhibitors of DNA methylation such as 5 azacytidine (5 AC) and 5-aza 2
      deoxycytidine (Decitabine). The review also provides an update on the rationale
      and results obtained from the combination therapy using histone deacetylases
      (HDAC) and DNA methyltransferase inhibitors in the treatment of MDS. In Section
      III, Professor Ghulam Mufti and Dr. Aloysius Ho describe the role of bone marrow
      transplantation with particular emphasis on recent results from reduced-intensity
      conditioned transplants, exploiting the graft versus leukemia effect without
      significant early treatment-related mortality. The section provides an update on
      the results obtained from the manipulation of the host's immune system with
      immunosuppressive agents such as ALG and/or cyclosporine A.

PMID- 14633783
TI  - Chronic myeloproliferative disorders.
AB  - The Philadelphia chromosome-negative chronic myeloproliferative disorders (CMPD),
      polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic
      myelofibrosis (IMF), have overlapping clinical features but exhibit different
      natural histories and different therapeutic requirements. Phenotypic mimicry
      amongst these disorders and between them and nonclonal hematopoietic disorders,
      lack of clonal diagnostic markers, lack of understanding of their molecular basis
      and paucity of controlled, prospective therapeutic trials have made the diagnosis
      and management of PV, ET and IMF difficult. In Section I, Dr. Jerry Spivak
      introduces current clinical controversies involving the CMPD, in particular the
      diagnostic challenges. Two new molecular assays may prove useful in the diagnosis
      and classification of CMPD. In 2000, the overexpression in PV granulocytes of the
      mRNA for the neutrophil antigen NBI/CD177, a member of the uPAR/Ly6/CD59 family
      of plasma membrane proteins, was documented. Overexpression of PRV-1 mRNA
      appeared to be specific for PV since it was not observed in secondary
      erythrocytosis. At this time, it appears that overexpression of granulocyte PRV-1
      in the presence of an elevated red cell mass supports a diagnosis of PV; absence
      of PRV-1 expression, however, should not be grounds for excluding PV as a
      diagnostic possibility. Impaired expression of Mpl, the receptor for
      thrombopoietin, in platelets and megakaryocytes has been first described in PV,
      but it has also been observed in some patients with ET and IMF. The biologic
      basis appears to be either alternative splicing of Mpl mRNA or a single
      nucleotide polymorphism, both of which involve Mpl exon 2 and both of which lead
      to impaired posttranslational glycosylation and a dominant negative effect on
      normal Mpl expression. To date, no Mpl DNA structural abnormality or mutation has
      been identified in PV, ET or IMF. In Section II, Dr. Tiziano Barbui reviews the
      best clinical evidence for treatment strategy design in PV and ET. Current
      recommendations for cytoreductive therapy in PV are still largely similar to
      those at the end of the PVSG era. Phlebotomy to reduce the red cell mass and keep
      it at a safe level (hematocrit < 45%) remains the cornerstone of treatment.
      Venesection is an effective and safe therapy and previous concerns about
      potential side effects, including severe iron deficiency and an increased
      tendency to thrombosis or myelofibrosis, were erroneous. Many patients require no
      other therapy for many years. For others, however, poor compliance to phlebotomy
      or progressive myeloproliferation, as indicated by increasing splenomegaly or
      very high leukocyte or platelet counts, may call for the introduction of
      cytoreductive drugs. In ET, the therapeutic trade-off between reducing thrombotic
      events and increasing the risk of leukemia with the use of cytoreductive drugs
      should be approached by patient risk stratification. Thrombotic deaths seem very
      rare in low-risk ET subjects and there are no data indicating that fatalities can
      be prevented by starting cytoreductive drugs early. Therefore, withholding
      chemotherapy might be justifiable in young, asymptomatic ET patients with a
      platelet count below 1500000/mm(3) and with no additional risk factors for
      thrombosis. If cardiovascular risk factors together with ET are identified
      (smoking, obesity, hypertension, hyperlipidemia) it is wise to consider platelet
      lowering agents on an individual basis. In Section III, Dr. Gianni Tognoni
      discusses the role of aspirin therapy in PV based on the recently completed
      European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study, a
      multi-country, multicenter project aimed at describing the natural history of PV
      as well as the efficacy of low-dose aspirin. Aspirin treatment lowered the risk
      of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke
      (relative risk 0.41 [95% CI 0.15-1.15], P =.0912). Total and cardiovascular
      mortality were also reduced by 46% and 59%, respectively. Major bleedings were
      slightly increased nonsignificnsignificantly by aspirin (relative risk 1.62, 95%
      CI 0.27-9.71). In Section IV, Dr. Giovanni Barosi reviews our current
      understanding of the pathophysiology of IMF and, in particular, the contributions
      of anomalous megakaryocyte proliferation, neoangiogenesis and abnormal CD34(+)
      stem cell trafficking to disease pathogenesis. The role of newer therapies, such
      as low-conditioning stem cell transplantation and thalidomide, is discussed in
      the context of a general treatment strategy for IMF. The results of a Phase II
      trial of low-dose thalidomide as a single agent in 63 patients with myelofibrosis
      with meloid metaplasia (MMM) using a dose-escalation design and an overall low
      dose of the drug (The European Collaboration on MMM) will be presented.
      Considering only patients who completed 4 weeks of treatment, 31% had a response:
      this was mostly due to a beneficial effect of thalidomide on patients with
      transfusion dependent anemia, 39% of whom abolished transfusions, patients with
      moderate to severe thrombocytopenia, 28% of whom increased their platelet count
      by more than 50 x 10(9)/L, and patients with the largest splenomegalies, 42% of
      whom reduced spleen size of more than 2 cm.

PMID- 14633784
TI  - Hodgkin's lymphoma: biology and treatment strategies for primary, refractory, and
      relapsed disease.
AB  - Hodgkin's lymphomas belong to the most curable tumor diseases in adults. About
      80% of patients in all anatomical stages and of all histological subtypes can be
      cured with modern treatment strategies. In spite of the great clinical progress,
      the pathogenesis of this peculiar lymphoproliferative entity has not been
      elucidated completely up until now. In Section I Drs. Stein, Hummel, and
      Zollinger describe the different pro-proliferative and antiapoptotic pathways and
      molecules involved in the transformation of the germinal center B-lymphocyte to
      the malignant Hodgkin-Reed-Sternberg cell. They use a comprehensive gene
      expression profiling (Affymetrix gene chip U133A) on B- and T-Hodgkin cell lines
      and state that the cell of origin is not the dominant determinant of the Hodgkin
      cell phenotype, but the transforming event. H-RS cells lack specific functional
      markers (B-T-cell receptors) and physiologically should undergo apoptosis. Why
      they do not is unclear and a matter of intensive ongoing research. In Section II
      Dr. Diehl summarizes the commonly used primary treatment strategies adapted to
      prognostic strata in early, intermediate and advanced anatomical stages using
      increasing intensities of chemotherapy (two, four, eight courses of chemotherapy
      such as ABVD) and additive radiation with decreased doses and field size. ABVD is
      without doubt the gold standard for early and intermediate stages, but its role
      as the standard regimen for advanced stages is challenged by recent data with
      time- and dose-intensified regimens such as the escalated BEACOPP, demonstrating
      superiority over COPP/ABVD (equivalent to ABVD) for FFTF and OS in all risk
      strata according to the International Prognostic Score. In Section III, Dr.
      Connors states that fortunately there is a considerably decreased need for
      salvage strategies in Hodgkin's lymphomas since primary treatment results in a
      more than 80% tumor control. Nevertheless, a significant number of patients
      experience either a tumor refractory to therapy or an early or late relapse.
      Therefore, one of the continuing challenges in the care for Hodgkin's lymphomas
      today is to find effective modes for a second tumor control. High-dose
      chemotherapy followed by autologous stem cell support has proved to be the
      treatment of choice when disseminated tumors recur after primary chemo- and or
      radiotherapy. Nodal relapses respond well to local radiation when they recur
      outfield of primary radiation without B-symptoms and in stages I-II at relapse.
      Allogeneic stem cell support needs further intensive evaluation in controlled
      studies to become an established alternative.

PMID- 14633785
TI  - Advances in biology and therapy of multiple myeloma.
AB  - Even during this past year, further advances have been made in understanding the
      molecular genetics of the disease, the mechanisms involved in the generation of
      myeloma-associated bone disease and elucidation of critical signaling pathways as
      therapeutic targets. New agents (thalidomide, Revimid, Velcade) providing
      effective salvage therapy for end-stage myeloma, have broadened the therapeutic
      armamentarium markedly. As evidenced in Section I by Drs. Kuehl and Bergsagel,
      five recurrent primary translocations resulting from errors in IgH switch
      recombination during B-cell development in germinal centers involve 11q13 (cyclin
      D1), 4p16.3 (FGFR3 and MMSET), 6p21 (cyclin D3), 16q23 (c-maf), and 20q11 (mafB),
      which account for about 40% of all myeloma tumors. Based on gene expression
      profiling data from two laboratories, the authors propose 5 multiple myeloma (MM)
      subtypes defined by the expression of translocation oncogenes and cyclins (TC
      molecular classification of MM) with different prognostic implications. In
      Section II, Drs. Barille-Nion and Bataille review new insights into osteoclast
      activation through the RANK Ligand/OPG and MIP-1 chemokine axes and osteoblast
      inactivation in the context of recent data on DKK1. The observation that myeloma
      cells enhance the formation of osteoclasts whose activity or products, in turn,
      are essential for the survival and growth of myeloma cells forms the basis for a
      new treatment paradigm aimed at reducing the RANKL/OPG ratio by treatment with
      RANKL inhibitors and/or MIP inhibitors. In Section III, Dr. Fenton reviews
      apoptotic pathways as they relate to MM therapy. Defects in the mitochrondrial
      intrinsic pathway result from imbalances in expression levels of Bcl-2, Bcl-XL
      and Mcl-1. Mcl-1 is a candidate target gene for rapid induction of apoptosis by
      flavoperidol. Antisense oglionucleotides (ASO) lead to the rapid induction of
      caspace activity and apoptosis, which was potentiated by dexamethasone. Similar
      clinical trials with Bcl-2 ASO molecules alone and in combination with
      doxorubicin and dexamethasone or thalidomide showed promising results. The
      extrinsic pathway can be activated upon binding of the ligand TRAIL. OPG,
      released by osteoblasts and other stromal cells, can act as a decoy receptor for
      TRAIL, thereby blocking its apoptosis-inducing activity. MM cells inhibit OPG
      release by stromal cells, thereby promoting osteoclast activation and lytic bone
      disease (by enhancing RANKL availability) while at the same time exposing
      themselves to higher levels of ambient TRAIL. Thus, as a recurring theme, the
      relative levels of pro- versus anti-apoptotic molecules that act in a cell
      autonomous manner or in the milieu of the bone marrow microenvironment determine
      the outcome of potentially lethal signals. In Section IV, Dr. Barlogie and
      colleagues review data on single and tandem autotransplants for newly diagnosed
      myeloma. CR rates of 60%-70% can be reached with tandem transplants extending
      median survival to approximately 7 years. Dose adjustments of melphalan in the
      setting of renal failure and age > 70 may be required to reduce mucositis and
      other toxicities in such patients, especially in the context of amyloidosis with
      cardiac involvement. In Total Therapy II the Arkansas group is evaluating the
      role of added thalidomide in a randomized trial design. While data are still
      blinded as to the contribution of thalidomide, the overriding adverse importance
      of cytogenetic abnormalities, previously reported for Total Therapy I, also
      pertain to this successor trial. In these two-thirds of patients without
      cytogenetic abnormalities, Total Therapy II effected a doubling of the 4-year EFS
      estimate from 37% to 75% (P <.0001) and increased the 4-year OS estimate from 63%
      to 84% (P =.0009). The well-documented graft-vs-MM effect of allotransplants can
      be more safely examined in the context of non-myeloablative regimens, applied as
      consolidation after a single autologous transplant with melphalan 200 mg/m(2),
      have been found to be much better tolerated than standard myeloablative
      conditioning rege conditioning regimens and yielding promising results even in
      the high-risk entity of MM with cytogenetic abnormalities. For previously treated
      patients, the thalidomide congener Revimid and the proteasome inhibitor Velcade
      both are active in advanced and refractory MM (approximately 30% PR). Gene
      expression profiling (GEP) has unraveled distinct MM subtypes with different
      response and survival expectations, can distinguish the presence of or future
      development of bone disease, and, through serial investigations, can elucidate
      mechanisms of actions of new agents also in the context of the bone marrow
      microenvironment. By providing prognostically relevant distinction of MM
      subgroups, GEP should aid in the development of individualized treatment for MM.

PMID- 14633786
TI  - Molecular diagnostics.
AB  - It is increasingly evident that molecular diagnostics, that is, the use of
      diagnostic testing to understand the molecular mechanisms of an individual
      patient's disease, will be pivotal in the delivery of safe and effective therapy
      for many diseases in the future. A huge body of new information on the genetic,
      genomic and proteomic profiles of different hematopoietic diseases is
      accumulating. This chapter focuses on new technologies and advancements in
      understanding the molecular basis of hematologic disorders, providing an overview
      of new information and its significance to patient care. In Section I, Dr.
      Braziel discusses the impact of new genetic information and research technologies
      on the actual practice of diagnostic molecular hematopathology. Recent and
      projected changes in methodologies and analytical strategies used by clinical
      molecular diagnostics laboratories for the evaluation of hematologic disorders
      will be discussed, and some of the challenges to clinical implementation of new
      molecular information and techniques will be highlighted. In Section II, Dr.
      Shipp provides an update on current scientific knowledge in the genomic profiling
      of malignant lymphomas, and describes some of the technical aspects of gene
      expression profiling. Analysis methods and the actual and potential clinical and
      therapeutic applications of information obtained from genomic profiling of
      malignant lymphomas are discussed. In Section III, Dr. Liotta presents an update
      on proteomic analysis, a new and very active area of research in hematopoietic
      malignancies. He describes new technologies for rapid identification of different
      important proteins and protein networks, and the potential therapeutic and
      prognostic value of the elucidation of these proteins and protein pathways in the
      clinical care of patients with malignant lymphomas.

PMID- 14633787
TI  - Human immunodeficiency virus hematology.
AB  - The advent of potent antiretroviral therapy has altered the expected natural
      history of human immunodeficiency virus (HIV) infection and of many previously
      associated opportunistic complications, including malignancies. At the same time,
      HIV suppression has not affected all of these complications equally and the
      longer expected survival of infected patients may allow the development of newer
      complications. Additionally, the use of potent antiretroviral combination therapy
      may itself lead to hematological toxicities. Together these changes affect the
      consultation role of the hematology-oncology specialist in comprehensive HIV care
      and demand ongoing education. In Section I, Dr. Paul Volberding reviews the
      biology of antiretroviral drug development and the progression in discovering new
      agents as the viral life cycle is further elucidated. He briefly summarizes the
      process of combining agents to achieve the degree of viral suppression required
      for long-term clinical benefit. In Section II, Dr. Kelty Baker reviews the
      effects of HIV and its therapy on hematologic dyscrasia and clotting disorders.
      She summarizes how therapy may decrease certain previously common manifestations
      of HIV disease while adding new problems likely to result in referral to the
      hematologist. In addition, she addresses the role of secondary infections, such
      as parvovirus, in this spectrum of disorders. In Section III, Dr. Alexandra
      Levine discusses the still challenging aspects of HIV associated non-Hodgkin's
      lymphoma and the association between HIV infection and Hodgkin's disease. She
      addresses current controversies in the pathogenesis of HIV related lymphomas and
      summarizes a number of recent trials of combination chemotherapy, with or without
      monoclonal antibodies, in their management. Additionally, she reviews the complex
      relationship of HIV disease with multicentric Castleman's disease and recent
      attempts to manage this disorder.

PMID- 14633788
TI  - Immunodeficiency disorders.
AB  - Hematological complications occur frequently in patients with both primary and
      secondary immunodeficiency disorders. Anemia, thrombocytopenia or leukopenias may
      bring these individuals to the attention of hematologists. Conversely, evidence
      suggesting a lymphoproliferative disorder may be the cause for referral. This
      session will provide an update on the diagnosis and treatment of immunodeficiency
      diseases ranging from isolated defects in antibody production to the severe
      combined immunodeficiencies (SCID). Immunodeficiency diseases have traditionally
      been defined as defects in the development and function of T and B cells, the
      primary effector cells of specific cellular and humoral immunity. However, it has
      become increasingly evident that innate immune mechanisms contribute greatly to
      host defense, either through acting alone or by enhancing specific T and B cell
      responses. In Section I, Dr. Lewis Lanier reviews the burgeoning information on
      the extensive families of activating and inhibitory immunoreceptors that are
      expressed on NK cells, dendritic cells, T and B cells, and phagocytic cells. He
      provides an overview on the biological functions of these receptors in host
      defense. In Section II, Dr. Mary Ellen Conley defines the spectrum of antibody
      deficiency disorders, the most frequently occurring types of primary
      immunodeficiencies. She covers the different defects in B-cell development and
      function that lead to antibody deficiencies, and includes diagnosis and therapy
      of these disorders. In Section III, Dr. Jennifer Puck discusses the diagnosis and
      treatment of the different types of SCID. She describes the genetic basis for
      SCID, and the benefits, pitfalls, and complications of gene therapy and bone
      marrow transplantation in SCID patients.

PMID- 14633789
TI  - Immunotherapy of hematologic malignancy.
AB  - Over the past few years, improved understanding of the molecular basis of
      interactions between antigen presenting cells and effector cells and advances in
      informatics have both led to the identification of many candidate antigens that
      are targets for immunotherapy. However, while immunotherapy has successfully
      eradicated relapsed hematologic malignancy after allogeneic transplant as well as
      virally induced tumors, limitations have been identified in extending
      immunotherapy to a wider range of hematologic malignancies. This review provides
      an overview of three immunotherapy strategies and how they may be improved. In
      Section I, Dr. Stevenson reviews the clinical experience with genetic vaccines
      delivered through naked DNA alone or viral vectors, which are showing promise in
      clinical trials in lymphoma and myeloma patients. She describes efforts to
      manipulate constructs genetically to enhance immunogenicity and to add additional
      elements to generate a more sustained immune response. In Section II, Dr.
      Molldrem describes clinical experience with peptide vaccines, with a particular
      focus on myeloid tissue-restricted proteins as GVL target antigens in CML and
      AML. Proteinase 3 and other azurophil granule proteins may be particularly good
      targets for both autologous and allogeneic T-cell responses. The potency of
      peptide vaccines may potentially be increased by genetically modifying peptides
      to enhance T-cell receptor affinity. Finally, in Section III, Dr. Heslop reviews
      clinical experience with adoptive immunotherapy with T cells. Transferred T cells
      have clinical benefit in treating relapsed malignancy post transplant, and
      Epstein-Barr virus associated tumors. However, T cells have been less successful
      in treating other hematologic malignancies due to inadequate persistence or
      expansion of adoptively transferred cells and the presence of tumor evasion
      mechanisms. An improved understanding of the interactions of antigen presenting
      cells with T cells should optimize efforts to manufacture effector T cells, while
      manipulation of lymphocyte homeostasis in vivo and development of gene therapy
      approaches may enhance the persistence and function of adoptively transferred T
      cells.

PMID- 14633790
TI  - New developments in allotransplant immunology.
AB  - After allogeneic stem cell transplantation, the establishment of the donor's
      immune system in an antigenically distinct recipient confers a therapeutic graft
      versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and
      protracted immune dysfunction. In the last decade, a molecular-level description
      of alloimmune interactions and the process of immune recovery leading to
      tolerance has emerged. Here, new developments in understanding alloresponses,
      genetic factors that modify them, and strategies to control immune reconstitution
      are described. In Section I, Dr. John Barrett and colleagues describe the
      cellular and molecular basis of the alloresponse and the mechanisms underlying
      the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL)
      effect. Increasing knowledge of leukemia-restricted antigens suggests ways to
      separate GVHD and GVL. Recent findings highlight a central role of hematopoietic
      derived antigen-presenting cells in the initiation of GVHD and distinct
      properties of natural killer (NK) cell alloreactivity in engraftment and GVL that
      are of therapeutic importance. Finally, a detailed map of cellular immune
      recovery post-transplant is emerging which highlights the importance of post
      thymic lymphocytes in determining outcome in the critical first few months
      following stem cell transplantation. Factors that modify immune reconstitution
      include immunosuppression, GVHD, the cytokine milieu and poorly-defined
      homeostatic mechanisms which encourage irregular T cell expansions driven by
      immunodominant T cell-antigen interactions. In Section II, Prof. Anne Dickinson
      and colleagues describe genetic polymorphisms outside the human leukocyte antigen
      (HLA) system that determine the nature of immune reconstitution after allogeneic
      stem cell transplantation (SCT) and thereby affect transplant outcomethrough
      GVHD, GVL, and transplant-related mortality. Polymorphisms in cytokine gene
      promotors and other less characterized genes affect the cytokine milieu of the
      recipient and the immune reactivity of the donor. Some cytokine gene
      polymorphisms are significantly associated with transplant outcome. Other non-HLA
      genes strongly affecting alloresponses code for minor histocompatibility antigens
      (mHA). Differences between donor and recipient mHA cause GVHD or GVL reactions or
      graft rejection. Both cytokine gene polymorphisms (CGP) and mHA differences
      resulting on donor-recipient incompatibilities can be jointly assessed in the
      skin explant assay as a functional way to select the most suitable donor or the
      best transplant approach for the recipient. In Section III, Dr. Nelson Chao
      describes non-pharmaceutical techniques to control immune reconstitution post
      transplant. T cells stimulated by host alloantigens can be distinguished from
      resting T cells by the expression of a variety of activation markers (IL-2
      receptor, FAS, CD69, CD71) and by an increased photosensitivity to rhodamine
      dyes. These differences form the basis for eliminating GVHD-reactive T cells in
      vitro while conserving GVL and anti-viral immunity. Other attempts to control
      immune reactions post-transplant include the insertion of suicide genes into the
      transplanted T cells for effective termination of GVHD reactions, the removal of
      CD62 ligand expressing cells, and the modulation of T cell reactivity by favoring
      Th2, Tc2 lymphocyte subset expansion. These technologies could eliminate GVHD
      while preserving T cell responses to leukemia and reactivating viruses.

PMID- 14633791
TI  - Hematopoietic cell transplantation for benign hematological disorders and solid
      tumors.
AB  - Allogeneic hematopoietic cell transplantation (HCT) has been successfully used as
      replacement therapy for patients with aplastic anemia and hemoglobinopathies.
      Both autologous and allogeneic HCT following high-dose chemotherapy can correct
      manifestations of autoimmune diseases. The impressive allogeneic graft-versus
      tumor effects seen in patients given HCT for hematological malignancies have
      stimulated trials of allogeneic immunotherapy in patients with otherwise
      refractory metastatic solid tumors. This session will update the status of HCT in
      the treatment of benign hematological diseases and solid tumors. In Section I,
      Dr. Rainer Storb reviews the development of nonmyeloablative conditioning for
      patients with severe aplastic anemia who have HLA-matched family members. He also
      describes the results in patients with aplastic anemia given HCT from unrelated
      donors after failure of responding to immunosuppressive therapy. The importance
      of leuko-poor and in vitro irradiated blood product transfusions for avoiding
      graft rejection will be discussed. In Section II, Dr. Guido Lucarelli reviews the
      status of marrow transplantation for thalassemia major and updates results
      obtained in children with class I and class II severity of thalassemia. He also
      describes results of new protocols for class III patients and efforts to extend
      HCT to thalassemic patients without HLA-matched family members. In Section III,
      Dr. Peter McSweeney reviews the current status of HCT for severe autoimmune
      diseases. He summarizes the results of autologous HCT for systemic sclerosis,
      multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, and
      reviews the status of planned Phase III studies for autologous HCT for these
      diseases in North America and Europe. He also discusses a possible role of
      allogeneic HCT in the treatment of these diseases. In Section IV, Dr. Richard
      Childs discusses the development and application of nonmyeloablative HCT as
      allogeneic immunotherapy for treatment-refractory solid tumors. He reviews the
      results of pilot clinical trials demonstrating graft-versus-solid tumor effects
      in a variety of metastatic cancers and describes efforts to characterize the
      immune cell populations mediating these effects, as well as newer methods to
      target the donor immune system to the tumor.

PMID- 14633792
TI  - Realistic prospects for stem cell therapeutics.
AB  - Studies of the regenerating hematopoietic system have led to the definition of
      many of the fundamental principles of stem cell biology. Therapies based on a
      range of tissue stem cells have been widely touted as a new treatment modality,
      presaging an emerging new specialty called regenerative medicine that promises to
      harness stem cells from embryonic and somatic sources to provide replacement cell
      therapies for genetic, malignant, and degenerative conditions. Insights borne
      from stem cell biology also portend development of protein and small molecule
      therapeutics that act on endogenous stem cells to promote repair and
      regeneration. Much of the newfound enthusiasm for regenerative medicine stems
      from the hope that advances in the laboratory will be followed soon thereafter by
      breakthrough treatments in the clinic. But how does one sort through the hype to
      judge the true promise? Are stem cell biologists and the media building
      expectations that cannot be met? Which diseases can be treated, and when can we
      expect success? In this review, we outline the realms of investigation that are
      capturing the most attention, and consider the current state of scientific
      understanding and controversy regarding the properties of embryonic and somatic
      (adult) stem cells. Our objective is to provide a framework for appreciating the
      promise while at the same time understanding the challenges behind translating
      fundamental stem cell biology into novel clinical therapies.

PMID- 14633793
TI  - Stem cell mobilization.
AB  - Successful blood and marrow transplant (BMT), both autologous and allogeneic,
      requires the infusion of a sufficient number of hematopoietic progenitor/stem
      cells (HPCs) capable of homing to the marrow cavity and regenerating a full array
      of hematopoietic cell lineages in a timely fashion. At present, the most commonly
      used surrogate marker for HPCs is the cell surface marker CD34, identified in the
      clinical laboratory by flow cytometry. Clinical studies have shown that infusion
      of at least 2 x 10(6) CD34(+) cells/kg recipient body weight results in reliable
      engraftment as measured by recovery of adequate neutrophil and platelet counts
      approximately 14 days after transplant. Recruitment of HPCs from the marrow into
      the blood is termed mobilization, or, more commonly, stem cell mobilization. In
      Section I, Dr. Tsvee Lapidot and colleagues review the wide range of factors
      influencing stem cell mobilization. Our current understanding focuses on
      chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cell
      stem cell interactions. On the basis of this understanding, new approaches to
      mobilization have been designed and are now starting to undergo clinical testing.
      In Section II, Dr. Michele Cottler-Fox describes factors predicting the ability
      to mobilize the older patient with myeloma. In addition, clinical approaches to
      improving collection by individualizing the timing of apheresis and adjusting the
      volume of blood processed to achieve a desired product are discussed. Key to this
      process is the daily enumeration of blood CD34(+) cells. Newer methods of
      enumerating and mobilizing autologous blood HPCs are discussed. In Section III,
      Dr. John DiPersio and colleagues provide data on clinical results of mobilizing
      allogeneic donors with G-CSF, GM-CSF and the combination of both as relates to
      the number and type of cells collected by apheresis. Newer methods of stem cell
      mobilization as well as the relationship of graft composition on immune
      reconstitution and GVHD are discussed.

PMID- 14633794
TI  - Infections in patients with hematological cancer: recent developments.
AB  - One of the most common complications involved in treating patients with
      hematologic cancer is infection. In many cases there are multiple factors that
      predispose these patients to infections such as neutropenia induced by therapy or
      bone marrow involvement, hypogammaglobulinemia, T-cell dysfunction, and mucosal
      damage. In addition, newer therapies have changed the spectrum of infection that
      is seen in these patients. In Section I, Dr. Blijlevens discusses mucosal damage
      as a major risk factor for complications of cytotoxic chemotherapy. She focuses
      on mucosal barrier injury (MBI) as manifest in the GI tract and will describe a
      pathological model to explain MBI, evaluate risk factors for development of this
      syndrome, explain the relationship between MBI and infection, and discuss
      treatment and prevention of this injury. Invasive fungal infections continue to
      represent a significant problem in patients with hematologic cancer. In Section
      II, Drs. Anaissie and Mahfouz review the latest developments in the diagnosis,
      prevention, and management of invasive fungal infections with a focus on a risk
      adjusted approach to this problem. Finally, in Section III, Dr. O'Brien reviews
      infections associated with newer therapeutic regimens in hematologic cancers. The
      spectrum of infections has changed with the use of purine analogs and the advent
      of monoclonal antibodies. The profound T-cell suppression associated with these
      therapies has led to the emergence of previously rare infections such as
      cytomegalovirus. An approach to both prophylaxis and management of these
      infections is discussed.

PMID- 14633795
TI  - The hematologist and radiation casualties.
AB  - Since the terrorist attack of September 11, 2001, preparation by the health care
      system for an act of terrorism has been mandated by leaders of governments.
      Scenarios for terrorist acts involving radioactive material have been identified,
      and approaches to management (based on past experience from atomic weapons
      detonations and radiation accidents) have been developed. Because of their
      experience in managing patients with profound cytopenia and/or marrow aplasia,
      hematologists will be asked to play a significant role in evaluating and treating
      victims of mass accidental or deliberate exposure to radiation. This review
      provides a framework for understanding how radiation levels are quantified, how
      radiation alters the function of hematopoietic (and nonhematopoietic) cells and
      tissues, and how victims receiving a significant radiation dose can be identified
      and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the
      Acute Radiation Syndrome: the hematopoietic, neurovascular, gastrointestinal and
      cutaneous subsyndromes. Clinical signs and symptoms are discussed for exposed
      individuals at the time of initial presentation (the prodromal phase) and during
      their course of disease (the manifest illness). In Section II, he presents
      clinical and laboratory methods to assess radiation doses, including time to
      onset and severity of vomiting, rate of decline in absolute blood lymphocyte
      count and the appearance of chromosome aberrations such as dicentrics and ring
      forms. Potential scenarios of a radiation terrorist event are reviewed, and
      methods for initial clinical assessment, triage, and early management of the
      acute radiation syndrome and its component subsyndromes are summarized. In
      Section III, Dr. Jamie Waselenko reviews the hematopoietic syndrome, and presents
      guidelines for the use of cytokine therapy, antibiotics, and supportive care that
      have been developed by the Strategic National Pharmaceutical Stockpile Working
      Group. Results of preclinical and clinical growth factor therapy studies with G
      CSF, GM-CSF, pegylated G-CSF, SCF, and IL-3 are summarized. When and how
      potassium iodide should be used after exposure to radioiodines is also reviewed.
      In Section IV, Dr. James Armitage describes a narrow "window" of 7 to 10 Gy where
      therapy with stem cell transplantation may be appropriate. Victims who are
      candidates for allotransplantation should not have major trauma or significant
      injury to other (nonhematopoietic) tissues. Rarely, victims may have an identical
      sibling or autologous stored marrow or blood stem cells, in which case the
      threshold for transplantation is 4 Gy. In Section V, Dr. Thomas MacVittie
      describes new directions for therapy, using cytokines such as IL-7, keratinocyte
      growth factor, and FLT-3. The potential for combinations of cytokines to enhance
      hematopoietic recovery is also reviewed.

PMID- 14633796
TI  - Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome.
AB  - Acquired abnormalities in platelets, endothelium, and their interaction occur in
      sepsis, immune heparin-induced thrombocytopenia (HIT), and the antiphospholipid
      syndrome. Although of distinct pathogeneses, these three disorders have several
      clinical features in common, including thrombocytopenia and the potential for
      life- and limb-threatening thrombotic events, ranging from microvascular (sepsis
      > antiphospholipid > HIT) to macrovascular (HIT > antiphospholipid > sepsis)
      thrombosis, both venous and arterial. In Section I, Dr. William Aird reviews
      basic aspects of endothelial-platelet interactions as a springboard to
      considering the common problem of thrombocytopenia (and its mechanism) in sepsis.
      The relationship between thrombocytopenia and other aspects of the host response
      in sepsis, including activation of coagulation/inflammation pathways and the
      development of organ dysfunction, is discussed. Practical issues of platelet
      count triggers and targeted use of activated protein C concentrates are reviewed.
      In Section II, Dr. Theodore Warkentin describes HIT as a clinicopathologic
      syndrome, i.e., the diagnosis should be based on the concurrence of an
      appropriate clinical picture together with detection of platelet-activating
      and/or platelet factor 4-dependent antibodies (usually in high levels). HIT is a
      profound prothrombotic state (odds ratio for thrombosis, 20-40), and the risk for
      thrombosis persists for a time even when heparin is stopped. Thus, pharmacologic
      control of thrombin (or its generation), and postponing oral anticoagulation
      pending substantial resolution of thrombocytopenia, is appropriate. Indeed,
      coumarin-associated protein C depletion during uncontrolled thrombin generation
      of HIT can explain limb loss (coumarin-associated venous limb gangrene) or skin
      necrosis syndromes in some patients. In Section III, Dr. Jacob Rand presents the
      most recent concepts on the mechanisms of thrombosis in the antiphospholipid
      syndrome, and focuses on the role of beta(2)-glycoprotein I as a major antigenic
      target in this condition. Diagnosis of the syndrome is often complicated because
      the clinical laboratory tests to identify this condition have been empirically
      derived. Dr. Rand addresses the practical aspects of current testing for the
      syndrome and current recommendations for treating patients with thrombosis and
      with spontaneous pregnancy losses.

PMID- 14633797
TI  - Thrombotic disorders: diagnosis and treatment.
AB  - Hematologists are increasingly involved in the diagnosis and management of
      patients with venous and arterial thromboembolic disorders. There have been major
      advances in recent years in our understanding of the central role of
      hypercoagulability in the pathogenesis of thrombosis. This has led to new
      approaches to the diagnosis of patients at risk for thrombosis and the
      development of more rational antithrombotic strategies. In Section I, Dr. Andrew
      Schafer reviews current concepts of acquired and inherited hypercoagulable
      states. It is now recognized that most, if not all, patients with venous
      thromboembolism have a genetic basis for the disorder ("thrombophilia"). The
      level of lifelong, baseline hypercoagulability in any individual may be
      determined by the type(s) and number of thrombophilia(s) that are inherited.
      Clinical episodes of thrombosis are precipitated by acquired thrombogenic
      triggers, which may be overt (e.g., pregnancy) or subclinical. In Section II, Dr.
      Mark Levine discusses the complex problem of thrombosis in patients with cancer.
      The goals of treating acute venous thromboembolism in cancer patients are to
      prevent recurrence, minimize the risk of anticoagulant-induced bleeding, and
      improve quality of life. New developments have improved treatment of venous
      thromboembolism in these patients, including outpatient therapy and secondary
      prevention with low-molecular-weight heparin. In Section III, Dr. Barbara Konkle
      reviews the diagnosis and management of thrombotic complications associated with
      pregnancy and hormonal therapy. Patient management is discussed based on data on
      thrombotic risks associated with hormonal treatment of infertility, pregnancy and
      the post-partum period in women with and without underlying thrombophilic risk
      factors. In Section IV, Dr. Clive Kearon discusses the management of
      anticoagulation before and after elective surgery. In the past, there has been no
      consensus on the perioperative management of anticoagulation for patients who
      require long-term warfarin therapy. This review considers the expected risks and
      benefits of different approaches to anticoagulation in patients who require
      warfarin because of atrial fibrillation, a mechanical heart valve, or a history
      of venous thromboembolism.

PMID- 14633798
TI  - Consultations on patients with venous or arterial diseases.
AB  - Advances in vascular biology and drug development, as well as improved
      interventional techniques, are yielding multiple new treatments for patients with
      venous and/or arterial thrombosis. Hematologists who are providing consultations
      for these patients often participate in a multidisciplinary approach to provide
      optimal care. New anticoagulants, simplified and validated tests for detecting
      vascular disease, and improved interventional procedures can all reduce the
      morbidity and mortality that result from venous and arterial thrombosis. In this
      chapter, different aspects of the diagnosis and treatment of these disorders are
      addressed by a hematologist, an expert in vascular medicine, and a vascular
      surgeon. The key to the prevention and treatment of venous and arterial
      thrombosis is anticoagulant and antiplatelet therapy. In Section I, Dr. Charles
      Francis, a hematologist with expertise in thrombosis and hemostasis, describes
      the clinical trials that have resulted in the approval of newer anticoagulants
      such as fondaparinux and the thrombin- specific inhibitors. He also reviews the
      clinical trials that have shown the efficacy of the new oral anticoagulant
      ximelagatran. Although currently under study primarily for the prevention and
      treatment of venous thrombosis, these anticoagulants are likely to undergo
      evaluation for use in arterial thrombosis. Peripheral arterial disease (PAD),
      which affects as many as 12% of individuals over the age of 65 years, provides a
      diagnostic and therapeutic challenge to physicians across multiple
      subspecialties. Dr. William Hiatt, a specialist in vascular medicine, discusses
      in Section II the epidemiology and manifestations of PAD, the best ways in which
      to diagnose this disorder and determine its severity, and the most appropriate
      pharmacologic treatment. In Section III, Dr. Mark Jackson, a vascular surgeon,
      describes interventional procedures that have been developed or are under
      development to treat arterial thrombosis. He also reviews the status of inferior
      vena caval filters that are retrievable.

PMID- 14633799
TI  - Congenital bleeding disorders.
AB  - Both clinical and basic problems related to the congenital bleeding disorders
      continue to confront hematologists. On the forefront are efforts to bring genetic
      correction of the more common bleeding disorders such as hemophilia A to the
      clinic in a safe and accessible manner. A second issue, particularly for patients
      with hemophilia, is the development of inhibitors-questions of how they arise and
      how to prevent and treat these problems that confound otherwise very successful
      replacement therapy and allow patients to maintain normal lifestyles. A third
      issue is the continuing question of diagnosis and management of von Willebrand
      disease, the most common congenital bleeding disorder, especially in individuals
      who have borderline laboratory values, but have a history of clinical bleeding.
      In Section I, Dr. Christopher Walsh discusses general principles of effective
      gene transfer for the hemophilias, specific information about viral vectors and
      non-viral gene transfer, and alternative target tissues for factor VIII and
      factor IX production. He highlights information about the immune response to gene
      transfer and reviews data from the hemophilia gene transfer trials to date. The
      future prospects for newer methods of therapy such as RNA repair and the use of
      gene-modified circulating endothelial progenitors are presented as possible
      alternatives to the more traditional gene therapy approaches. In Section II, Dr.
      Nigel Key focuses on inhibitor development in patients with hemophilia A. He
      reviews the progress in our understanding of the risk factors and presents newer
      information about the immunobiology of inhibitor development. He discusses the
      natural history of these inhibitors and the screening, laboratory diagnosis, and
      treatment, including the use of different modalities for the treatment of acute
      bleeding episodes. Dr. Key also presents information about the eradication of
      inhibitors by immune tolerance induction and reviews recent information from the
      international registries regarding the status and success of immune tolerance
      induction. In Section III, Dr. Margaret Rick discusses the diagnosis,
      classification, and management of von Willebrand disease. Attention is given to
      the difficulty of diagnosis in patients with mild bleeding histories and
      borderline laboratory test results for von Willebrand factor. She presents the
      value of different laboratory assays for both diagnosis and classification, and
      she relates the classification of von Willebrand disease to the choice of
      treatment and to the known genetic mutations. Practical issues of diagnosis and
      treatment, including clinical cases, will be presented.

PMID- 14633800
TI  - Bacterial contamination of blood components: risks, strategies, and regulation:
      joint ASH and AABB educational session in transfusion medicine.
AB  - Bacterial contamination of transfusion products, especially platelets, is a
      longstanding problem that has been partially controlled through modern phlebotomy
      practices, refrigeration of red cells, freezing of plasma and improved materials
      for transfusion product collection and storage. Bacterial contamination of
      platelet products has been acknowledged as the most frequent infectious risk from
      transfusion occurring in approximately 1 of 2000-3000 whole-blood derived, random
      donor platelets, and apheresis-derived, single donor platelets. In the US,
      bacterial contamination is considered the second most common cause of death
      overall from transfusion (after clerical errors) with mortality rates ranging
      from 1:20000 to 1:85000 donor exposures. Estimates of severe morbidity and
      mortality range from 100 to 150 transfused individuals each year. Concern over
      the magnitude and clinical relevance of this issue culminated in an open letter
      calling for the "blood collection community to immediately initiate a program for
      detecting the presence of bacteria in units of platelets." Thereafter, the
      American Association of Blood Banks (AABB) proposed new standards to help
      mitigate transfusion of units that were contaminated with bacteria. Adopted with
      a final implementation date of March 1, 2004, the AABB Standard reads "The blood
      bank or transfusion service shall have methods to limit and detect bacterial
      contamination in all platelet components." This Joint ASH and AABB Educational
      Session reviews the risks, testing strategies, and regulatory approaches
      regarding bacterial contamination of blood components to aid in preparing
      practitioners of hematology and transfusion medicine in understanding the
      background and clinical relevance of this clinically important issue and in
      considering the approaches currently available for its mitigation, as well as
      their implementation. In this chapter, Drs. Hillyer and Josephson review the
      background and significance of bacterial contamination, as well as address the
      definitions, conceptions and limitations of the terms risk, safe and safety. They
      then describe current transfusion risks including non-infectious serious hazards
      of transfusion, and current and emerging viral risks. In the body of the text,
      Dr. Blajchman reviews the prevalence of bacterial contamination in cellular blood
      components in detail with current references to a variety of important studies.
      He then describes the signs and symptoms of transfusion-associated sepsis and the
      sources of the bacterial contamination for cellular blood products including
      donor bacteremia, and contamination during whole blood collection and of the
      collection pack. This is followed by strategies to decrease the transfusion
      associated morbidity/mortality risk of contaminated cellular blood products
      including improving donor skin disinfection, removal of first aliquot of donor
      blood, pre-transfusion detection of bacteria, reducing recipient exposure, and
      pathogen reduction/inactivation. In the final sections, Drs. Vostal, Epstein and
      Goodman describe the regulations and regulatory approaches critical to the
      appropriate implementation of a bacterial contamination screening and limitation
      program including their and/or the FDA's input on prevention of bacterial
      contamination, bacterial proliferation, and detection of bacteria in transfusion
      products. This is followed by a discussion of sampling strategy for detection of
      bacteria in a transfusion product, as well as the current approval process for
      bacterial detection devices, trials recommended under "actual clinical use"
      conditions, pathogen reduction technologies, and bacterial detection and the
      extension of platelet storage.

PMID- 14633801
TI  - Hematology grants workshop.
AB  - Uppermost among the many concerns of young researchers is acquiring funding for
      beginning a career as a clinician-scientist. This chapter is targeted
      specifically at those individuals considering an academic physician-scientist
      career and those on the verge of becoming independent researchers. In Section I,
      Drs. Poncz and Iannone discuss the Mentored Career Development Award (K08). They
      summarize the application process, highlighting the critical components of a
      successful application and what the review process entails. In Section II, Dr.
      Werner discusses what applicants need to know about the NIH Institutes' program,
      review, and grants management function; the different NIH staff whom applicants
      should contact during the various stages of the grants process; and the important
      sections and key phrases in NIH Program Announcements for career development
      awards.

PMID- 14633803
TI  - Randomized controlled trial of a new dietary education program to prevent type 2
      diabetes in a high-risk group of Japanese male workers.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of a new dietary
      education (NDE) program in reducing plasma glucose (PG) levels in Japanese male
      workers at high risk for type 2 diabetes through a randomized controlled trial.
      RESEARCH DESIGN AND METHODS: We randomly assigned 173 high-risk men (mean age, 55
      years) to either the NDE or the control (conventional dietary education) group.
      Each subject in the NDE group received two individualized interventions
      especially aimed at reducing total energy intake at dinner by modifying dietary
      intake. The control group received conventional group counseling. An
      "overintake/underintake fraction" for total energy intake was used to measure the
      status of dietary intake. Our hypothesis was that the NDE group would have a 10%
      decrease in 2-h PG 1 year after the start of the education. Outcome measures were
      compared with ANCOVA by adjusting for baseline values. RESULTS: The NDE group had
      a significantly lower total energy intake at dinner and daily than the control
      group. The adjusted differences in changes from baseline in the absolute value of
      the 'overintake/underintake fraction' were -15.3% (95% CI -24.6 to -6.0%, P =
      0.002) for dinner and -6.0% (-9.8 to -2.2%, P = 0.002) for daily [corrected]. The
      NDE group had a decreased 2-h PG after 1 year, whereas that value was increased
      in the control group. The adjusted difference in the percent change of 2-h PG was
      significant (-15.2%, -22.0 to -8.4%, P < 0.001). CONCLUSIONS: The NDE was shown
      to reduce glucose levels in high-risk subjects for type 2 diabetes.

PMID- 14633804
TI  - Cinnamon improves glucose and lipids of people with type 2 diabetes.
AB  - OBJECTIVE: The objective of this study was to determine whether cinnamon improves
      blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL
      cholesterol levels in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A
      total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32
      years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3,
      or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo
      capsules corresponding to the number of capsules consumed for the three levels of
      cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout
      period. RESULTS: After 40 days, all three levels of cinnamon reduced the mean
      fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%),
      and total cholesterol (12-26%) levels; no significant changes were noted in the
      placebo groups. Changes in HDL cholesterol were not significant. CONCLUSIONS: The
      results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day
      reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in
      people with type 2 diabetes and suggest that the inclusion of cinnamon in the
      diet of people with type 2 diabetes will reduce risk factors associated with
      diabetes and cardiovascular diseases.

PMID- 14633805
TI  - Adiponectin in a native Canadian population experiencing rapid epidemiological
      transition.
AB  - OBJECTIVE: Adiponectin is emerging as an important protein in the etiology of
      obesity and related metabolic disorders. The objectives of this study were to
      determine cross-sectional and prospective associations of adiponectin
      concentration with adiposity, type 2 diabetes, and cardiovascular disease (CVD)
      risk factors in a population-based study of Native Canadians, a group
      experiencing dramatic increases in diabetes and CVD. RESEARCH DESIGN AND METHODS:
      During the 1993-1995 baseline survey, samples for glucose, insulin, adiponectin,
      and lipids were collected after an overnight fast. Waist circumference and
      percent body fat were measured, and a 75-g oral glucose tolerance test was
      administered: n = 505 with normal glucose tolerance (NGT), 74 with impaired
      glucose tolerance (IGT), and 149 with diabetes. In 1998, 95 high-risk subjects,
      defined as those who, at baseline, had either IGT or NGT with an elevated 2-h
      glucose concentration (>/==" BORDER="0">7.0 mmol/l), participated in a follow-up
      examination using the protocol used at baseline. RESULTS: After adjustment for
      covariates including percent body fat and homeostasis model assessment of insulin
      resistance (HOMA-IR), adiponectin concentrations were significantly lower among
      men versus women (10.8 vs. 15.0 micro g/ml, P < 0.0001) and among diabetic versus
      NGT subjects (11.1 vs. 13.1 micro g/ml, P < 0.05). Adiponectin was inversely
      correlated with percent body fat, waist circumference, HOMA-IR, and triglyceride
      and positively correlated with HDL (r = |0.30|-|0.44|, all P < 0.0001). In
      multivariate linear regression analysis in nondiabetic subjects, HDL and percent
      body fat were significantly related to adiponectin variation among both men and
      women (R(2) = 28-29%). Factor analysis returned three underlying factors among
      these variables, with adiponectin loading on the second factor along with
      insulin, waist circumference, triglyceride, and HDL. In the follow-up study,
      higher adiponectin at baseline was significantly associated with increases in HDL
      (r = 0.24, P = 0.03) and decreases in HOMA-IR (r = -0.29, P = 0.009) after
      adjustment for covariates, including age, adiposity, and diabetes status at
      baseline and follow-up. CONCLUSIONS: These population-based findings support the
      hypothesis that low circulating levels of adiponectin are an important
      determinant of risk of CVD.

PMID- 14633806
TI  - Plasma adiponectin is an independent predictor of type 2 diabetes in Asian
      indians.
AB  - OBJECTIVE: Adiponectin, secreted by fat cells, has regulatory functions on energy
      metabolism. Its low levels are predictive of future development of diabetes.
      Because no studies on the regulatory role of adiponectin in glucose homeostasis
      in Asian Indians exist, this analysis was performed to determine the prospective
      association of adiponectin and diabetes in subjects with impaired glucose
      tolerance (IGT). RESEARCH DESIGN AND METHODS: Baseline values of plasma
      adiponectin, results of anthropometry, fasting and 2-h plasma glucose levels,
      HbA(1c), results of lipid profile, and insulin resistance were analyzed in 91
      subjects with IGT (53 men and 38 women) in a primary prevention study.
      Reassessment of glucose tolerance was performed during 1-year review. The
      predictive nature of adiponectin for development of diabetes was assessed using
      univariate and multiple logistic regression analyses. A control group comprising
      healthy, normoglycemic individuals was used for comparison. RESULTS: At follow
      up, diabetes had developed in 25 of the 91 study subjects. The mean baseline
      adiponectin level was lower in the diabetic subjects than in the nondiabetic
      subjects (11.3 +/- 5.5 vs. 16.7 +/- 7.6 micro g/ml, P = 0.0017). Low adiponectin
      level was a strong predictor of future development of diabetes, and HbA(1c) also
      showed a positive predictive association. Women had higher adiponectin levels
      (16.4 +/- 6.1 micro g/ml) than men (13.9 +/- 7.6 micro g/ml) (P = 0.035).
      CONCLUSIONS: In Asian Indians, low plasma adiponectin level was predictive of
      future development of diabetes.

PMID- 14633807
TI  - The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year
      results on diet and physical activity.
AB  - OBJECTIVE: To describe the 1) lifestyle intervention used in the Finnish Diabetes
      Prevention Study, 2) short- and long-term changes in diet and exercise behavior,
      and 3) effect of the intervention on glucose and lipid metabolism. RESEARCH
      DESIGN AND METHODS: There were 522 middle-aged, overweight subjects with impaired
      glucose tolerance who were randomized to either a usual care control group or an
      intensive lifestyle intervention group. The control group received general
      dietary and exercise advice at baseline and had an annual physician's
      examination. The subjects in the intervention group received additional
      individualized dietary counseling from a nutritionist. They were also offered
      circuit-type resistance training sessions and advised to increase overall
      physical activity. The intervention was the most intensive during the first year,
      followed by a maintenance period. The intervention goals were to reduce body
      weight, reduce dietary and saturated fat, and increase physical activity and
      dietary fiber. RESULTS: The intervention group showed significantly greater
      improvement in each intervention goal. After 1 and 3 years, weight reductions
      were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control
      group, respectively. Measures of glycemia and lipemia improved more in the
      intervention group. CONCLUSIONS: The intensive lifestyle intervention produced
      long-term beneficial changes in diet, physical activity, and clinical and
      biochemical parameters and reduced diabetes risk. This type of intervention is a
      feasible option to prevent type 2 diabetes and should be implemented in the
      primary health care system.

PMID- 14633808
TI  - In utero dietary exposures and risk of islet autoimmunity in children.
AB  - OBJECTIVE: The goal of this study was to examine whether maternal dietary intake
      of vitamin D, omega-3 fatty acids, and omega-6 fatty acids during pregnancy is
      associated with the appearance of islet autoimmunity (IA) in offspring. RESEARCH
      DESIGN AND METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) is
      recruiting at birth and following children at increased risk for type 1 diabetes,
      as determined by HLA-DR genotype or by family history of type 1 diabetes. A total
      of 233 mothers of newly recruited DAISY subjects were asked to recall their
      intake of food and nutritional supplements during the third trimester of
      pregnancy using the Willett food frequency questionnaire. Children were followed
      for an average of 4 years (range 0.8-7.3 years) for the appearance of insulin,
      GAD(65), and IA-2 autoantibodies. Sixteen children developed at least one
      autoantibody during this period. Unadjusted and adjusted hazard ratios (HRs) for
      the development of IA were estimated with survival analysis using a Weibull
      distribution. RESULTS: Maternal intake of vitamin D via food was significantly
      associated with a decreased risk of IA appearance in offspring, independent of
      HLA genotype, family history of type 1 diabetes, presence of gestational diabetes
      mellitus, and ethnicity (adjusted HR = 0.37; 95% CI 0.17-0.78). Vitamin D intake
      via supplements, omega-3 fatty acids, and omega-6 fatty acids intake during
      pregnancy were not associated with appearance of IA in offspring. CONCLUSIONS:
      Our findings suggest that maternal intake of vitamin D through food during
      pregnancy may have a protective effect on the appearance of IA in offspring.

PMID- 14633809
TI  - Premenopausal advantages in postprandial lipid metabolism are lost in women with
      type 2 diabetes.
AB  - OBJECTIVE: Women with type 2 diabetes appear to lose the protection against
      cardiovascular disease afforded by estrogens. We examined the effects of
      menopausal status on postprandial clearance of dietary fat in healthy and
      diabetic women. RESEARCH DESIGN AND METHODS: Fasting subjects (premenopausal and
      postmenopausal control subjects, premenopausal and postmenopausal diabetic women,
      all n = 8) were given a meal containing the stable isotope 1,1,1-(13)C
      tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the
      postprandial period. Lower levels of (13)C-palmitic acid ((13)C-PA) in the
      triglyceride fraction implies more efficient chylomicron clearance, lower levels
      of (13)C-PA in the nonesterified fatty acid (NEFA) fraction implies improved
      dietary NEFA entrapment, and higher levels of (13)CO(2) in the breath denote more
      efficient of oxidation of dietary-derived lipid. RESULTS: In diabetic women,
      there were no differences between the pre- and postmenopausal groups for any of
      these parameters. In contrast, premenopausal control subjects, compared with
      postmenopausal control subjects, had lower (13)C-PA in the triglyceride fraction
      area under the curve (AUC) (premenopausal median [range] 25.2 [12.1-49.4 mmol/l]
      per 6 h, postmenopausal 48.5 [15.5-77.2 mmol/l] per 6 h; P < 0.01) and higher
      (13)CO(2) levels in the breath AUC (premenopausal 22.5 [18.0-31.5%] of
      administered dose, postmenopausal 17.2 [11.2-31.5%] of administered dose; P <
      0.01) with no difference between groups in levels of (13)C-PA in the NEFA
      fraction AUC. CONCLUSIONS: The premenopausal advantage in clearance of dietary
      lipid is not seen in premenopausal diabetic women. This is likely to promote an
      atherogenic lipoprotein profile and may contribute to the loss of cardiovascular
      disease protection seen in diabetic women.

PMID- 14633810
TI  - Racial variation in the control of diabetes among elderly medicare managed care
      beneficiaries.
AB  - OBJECTIVE: To examine racial variation in the poor control of GHb, a GHb value
      >9.5%, or GHb not tested in 1999 among Medicare beneficiaries aged 65-75 years
      enrolled in managed care plans. RESEARCH DESIGN AND METHODS: The National
      Committee on Quality Assurance provides person-level data regarding diabetes care
      services and control for Medicare beneficiaries enrolled in managed care to the
      Centers for Medicare and Medicaid Services (CMS). We merged this information with
      information on each individual's race, as well as other person-level and plan
      level characteristics obtained from CMS. Bivarate and multivariate analyses were
      performed. RESULTS: The overall rate of poor GHb control was 32.7%. The age- and
      sex-adjusted rate of poor control among whites was 32.0%. This rate was
      significantly higher than the rate among Asians (24.7%) but significantly lower
      than the rate among blacks (40.6%) and Hispanics (36.5%) (P < 0.001). An increase
      in the number of comprehensive diabetes care measures received by an individual
      was associated with a significantly lower percentage of individuals with poor GHb
      control in all race groups. After controlling for the individual-level, plan
      level, and diabetes care measure variables, the difference in GHb control between
      Asians and whites disappeared. However, blacks and Hispanics continued to have
      significantly higher rates of poor control than whites. CONCLUSIONS: There is
      room for significant reduction in the number of patients with poor control of GHb
      among all races, particularly among blacks and Hispanics.

PMID- 14633811
TI  - Diabetes is associated with subclinical functional limitation in nondisabled
      older individuals: the Health, Aging, and Body Composition study.
AB  - OBJECTIVE: The aim of this study was to examine the role of comorbid conditions
      and body composition in the association between diabetes and subclinical
      functional limitation, an indication of early functional decline, in well
      functioning older individuals. RESEARCH DESIGN AND METHODS: This was a cross
      sectional analysis of 3,075 well-functioning black and white men and women aged
      70-79 years, enrolled in the Health, Aging, and Body Composition study. Diabetes
      was defined by self-report and/or hypoglycemic medication use or fasting glucose
      >/=126 mg/dl. Subclinical functional limitation was defined using self-report of
      capacity and objective performance measures. Comorbid conditions were identified
      by self-reported diagnoses, medication use, and clinical measures. Body
      composition measures included anthropometry and total fat (dual X-ray
      absorptiometry). RESULTS: Of 2,926 participants, 1,252 (42.8%) had subclinical
      functional limitation at baseline. Among 2,370 individuals without diabetes, 40%
      had subclinical functional limitation, whereas the prevalence was 53% among the
      556 diabetic participants with an age/sex/race-adjusted odds ratio (OR) 1.70 (95%
      CI 1.40-2.06). This association remained significant when adjusted for body
      composition measures (OR 1.54 [1.26-1.88]), diabetes-related comorbidities, and
      other potential confounders (OR 1.40 [1.14-1.73]). In the fully adjusted model,
      consideration of HbA(1c) (< or >/=7%) and diabetes duration showed that poor
      glycemic control in diabetic individuals explained the association with
      subclinical functional limitation. CONCLUSIONS: In a well-functioning older
      population, diabetes is associated with early indicators of functional decline,
      even after accounting for body composition and diabetes-related comorbidities.
      Poor glycemic control contributes to this relationship. Whether improvement in
      glycemic control in older people with diabetes would change this association
      should be tested.

PMID- 14633812
TI  - Primary prevention of cardiovascular events with low-dose aspirin and vitamin E
      in type 2 diabetic patients: results of the Primary Prevention Project (PPP)
      trial.
AB  - OBJECTIVE: We investigated in general practice the efficacy of antiplatelets and
      antioxidants in primary prevention of cardiovascular events in people with type 2
      diabetes. RESEARCH DESIGN AND METHODS: The Primary Prevention Project (PPP) is a
      randomized, open trial with a two-by-two factorial design aimed to investigate
      low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of
      cardiovascular events in patients with one or more cardiovascular risk factors.
      The primary end point was a composite end point of cardiovascular death, stroke,
      or myocardial infarction. A total of 1,031 people with diabetes in the PPP, aged
      >/=50 years, without a previous cardiovascular event were enrolled by 316 general
      practitioners and 14 diabetes outpatient clinics. RESULTS: The PPP trial was
      prematurely stopped (after a median of 3.7 years) by the independent data safety
      and monitoring board because of a consistent benefit of aspirin compared with the
      control group in a population of 4,495 patients with one or more major
      cardiovascular risk factors. In diabetic patients, aspirin treatment was
      associated with a nonsignificant reduction in the main end point (relative risk
      [RR] = 0.90, 95% CI 0.50-1.62) and in total cardiovascular events (0.89, 0.62
      1.26) and with a nonsignificant increase in cardiovascular deaths (1.23, 0.69
      2.19). In nondiabetic subjects, RRs for the main end point, total cardiovascular
      events, and cardiovascular deaths were 0.59 (0.37-0.94), 0.69 (0.53-0.90), and
      0.32 (0.14-0.72), respectively. No significant reduction in any of the end points
      considered could be found with vitamin E in either diabetic or nondiabetic
      subjects. CONCLUSIONS: Our data suggest a lower effect of primary prevention of
      cardiovascular disease (CVD) with low-dose aspirin in diabetic patients as
      opposed to subjects with other cardiovascular risk factors. If confirmed, these
      findings might indicate that the antiplatelet effects of aspirin in diabetic
      patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation
      and thrombus formation, thus making the balance between benefits and harms of
      aspirin treatment unfavorable. Further large-scale trials investigating the role
      of aspirin in the primary prevention of CVD in diabetic patients are urgently
      needed.

PMID- 14633813
TI  - The combined effect of triple therapy with rosiglitazone, metformin, and insulin
      aspart in type 2 diabetic patients.
AB  - OBJECTIVE: Type 2 diabetes is caused by reduced insulin secretion and insulin
      resistance in skeletal muscle and liver. We tested the combination therapy with
      insulin aspart, rosiglitazone, and metformin with the purpose of treating all
      three defects in order to test the hypothesis that this "triple therapy" will
      normalize glucose metabolism. RESEARCH DESIGN AND METHODS: Sixteen obese type 2
      diabetic outpatients on human NPH or MIX (regular + NPH insulin) insulin twice
      daily were randomized to either triple therapy, i.e., insulin aspart (a rapid
      acting insulin analog) at meals, metformin (which improves hepatic insulin
      sensitivity), and rosiglitazone (which improves peripheral insulin sensitivity),
      or to continue their NPH or MIX insulin twice daily for 6 months. Insulin doses
      were adjusted in both groups based on algorithms. HbA(1c), insulin dose,
      hypoglycemic episodes, insulin sensitivity (clamp), hepatic glucose production
      (tracer), and diurnal profiles of plasma glucose and insulin were used in
      evaluating treatment. RESULTS: In the triple therapy group, HbA(1c) declined from
      8.8 to 6.8% (P < 0.01) without inducing severe hypoglycemic events. Postprandial
      hyperglycemia was generally avoided, and the diurnal profile of serum insulin
      showed fast and high peaks without any need to increase insulin dose. In the
      control group, the insulin dose was increased by 50%, but nevertheless both
      HbA(1c) and 24-h blood glucose profiles remained unchanged. Insulin sensitivity
      improved in both skeletal muscle and the liver in the triple therapy group,
      whereas no change was observed in the control group. CONCLUSIONS: We conclude
      that treatment of the three major pathophysiological defects in type 2 diabetic
      subjects by triple therapy significantly improved glucose metabolism in obese
      type 2 diabetic subjects.

PMID- 14633814
TI  - Enhancing sensation in diabetic neuropathic foot with mechanical noise.
AB  - OBJECTIVE: Localized low-level mechanical or electrical noise can significantly
      enhance tactile sensitivity in healthy young subjects and older adults. This
      phenomenon is termed stochastic resonance (SR). In this study, we examined the
      effect of SR on vibratory and tactile sensation in patients with moderate to
      severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 20
      subjects were included in the study. The vibration perception threshold (VPT)
      test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of
      the left foot and the big toe were determined under two mechanical noise stimulus
      conditions: null (no noise) condition and at 10% lower than each subject's
      mechanical noise threshold of perception. RESULTS: The baseline values (mean +/-
      SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 +/- 2.5, Neuropathy
      Disability Score (NDS) 5.0 +/- 2.1, VPT 24 +/- 11 V, and SWF threshold 5.6 +/-
      0.8 at the plantar surface of the foot and 5.3 +/- 0.9 at the big toe. The VPT
      improved significantly from 24 +/- 11 under null condition to 19 +/- 10 V with
      mechanical noise (P < 0.0001). Mechanical noise also significantly increased the
      number of detections of the SWF at the plantar surface of the foot (detection
      rate 66 +/- 11 vs. 59 +/- 15%, P < 0.02) but not at the big toe (63 +/- 10 vs. 61
      +/- 16%, P = NS). CONCLUSIONS: Mechanical noise stimulation improves vibration
      and tactile perception in diabetic patients with moderate to severe neuropathy.
      Additional studies are required to examine the effect of long-term noise
      stimulation on parameters of nerve function.

PMID- 14633815
TI  - Clinical efficacy of the first metatarsophalangeal joint arthroplasty as a
      curative procedure for hallux interphalangeal joint wounds in patients with
      diabetes.
AB  - OBJECTIVE: To evaluate the safety and efficacy of first metatarsophalangeal joint
      arthroplasty compared with standard, nonsurgical management of wounds at the
      plantar hallux interphalangeal joint in patients with diabetes. RESEARCH DESIGN
      AND METHODS: We evaluated 41 patients with ulcers classified as University of
      Texas Grade 1A or 2A at the plantar aspect of the hallux interphalangeal joint
      using a case-control model [correction]. Case subjects were patients treated with
      resectional arthroplasty and control subjects received standard nonsurgical care.
      Both groups received standard off-loading and wound care. Outcomes included time
      to healing, reulceration, infection, and amputation. RESULTS: The surgery group
      healed significantly faster than patients in the standard therapy group (standard
      67.1 +/- 17.1 versus surgery 24.2 +/- 9.9 days, P = 0.0001), and they had fewer
      recurrent ulcers (standard 35.0 versus surgery 4.8%, P = 0.02, odds ratio 7.6,
      95% CI 1.1-261.7) Both groups had similar rates of infection (standard 38.1
      versus surgery 40.0%, P = 0.9) and amputation (standard 10.0 versus surgery 4.8%,
      P = 0.5). CONCLUSIONS: Results suggest that resectional arthroplasty is a safe
      and effective procedure to treat wounds of the plantar hallux compared with
      nonsurgical therapy.

PMID- 14633816
TI  - Benefits and risks of solitary islet transplantation for type 1 diabetes using
      steroid-sparing immunosuppression: the National Institutes of Health experience.
AB  - OBJECTIVE: The aim of this study was to describe the National Institutes of
      Health's experience initiating an islet isolation and transplantation center,
      including descriptions of our first six recipients, and lessons learned. RESEARCH
      DESIGN AND METHODS: Six females with chronic type 1 diabetes, hypoglycemia
      unawareness, and no endogenous insulin secretion (undetectable serum C-peptide)
      were transplanted with allogenic islets procured from brain dead donors. To
      prevent islet rejection, patients received daclizumab, sirolimus, and tacrolimus.
      RESULTS: All patients noted less frequent and less severe hypoglycemia, and one
      half were insulin independent at 1 year. Serum C-peptide persists in all but one
      patient (follow-up 17-22 months), indicating continued islet function. Two major
      procedure-related complications occurred: partial portal vein thrombosis and
      intra-abdominal hemorrhage. While we observed no cytomegalovirus infection or
      malignancy, recipients frequently developed transient mouth ulcers, diarrhea,
      edema, hypercholesterolemia, weight loss, myelosuppression, and other symptoms.
      Three patients discontinued immunosuppressive therapy: two because of intolerable
      toxicity (deteriorating kidney function and sirolimus-induced pneumonitis) while
      having evidence for continued islet function (one was insulin independent) and
      one because of gradually disappearing islet function. CONCLUSIONS: We established
      an islet isolation and transplantation program and achieved a 50% insulin
      independence rate after at most two islet infusions. Our experience demonstrates
      that centers not previously engaged in islet transplantation can initiate a
      program, and our data and literature analysis support not only the promise of
      islet transplantation but also its remaining hurdles, which include the limited
      islet supply, procedure-associated complications, imperfect immunosuppressive
      regimens, suboptimal glycemia control, and loss of function over time.

PMID- 14633817
TI  - Kidney function during and after withdrawal of long-term irbesartan treatment in
      patients with type 2 diabetes and microalbuminuria.
AB  - OBJECTIVE: Irbesartan is renoprotective in patients with type 2 diabetes and
      microalbuminuria. Whether the observed reduction in microalbuminuria is
      reversible (hemodynamic) or persistent (glomerular structural/biochemical
      normalization) after prolonged antihypertensive treatment is unknown. Therefore,
      the present substudy of the Irbesartan in Patients with Type 2 Diabetes and
      Microalbuminuria Study (IRMA-2) investigated the reversibility of kidney function
      changes after withdrawal of 2 years' antihypertensive treatment. RESEARCH DESIGN
      AND METHODS: The substudy included 133 hypertensive type 2 diabetic patients with
      persistent microalbuminuria in IRMA-2, randomized to double-masked treatment with
      either placebo, irbesartan 150 mg, or irbesartan 300 mg o.d. for 2 years.
      Arterial blood pressure, overnight urinary albumin excretion rate, and glomerular
      filtration rate (GFR) were determined repeatedly. RESULTS: Baseline
      characteristics were similar in the placebo, irbesartan 150-mg, and irbesartan
      300-mg groups. At the end of the study, mean arterial blood pressure (MABP) was
      similarly lowered to 105 +/- 2 (mean +/- SE), 103 +/- 2, and 102 +/- 2 mmHg,
      respectively (P < 0.05 versus baseline), and urinary albumin excretion rate
      reduced by 8% (-16 to 27) (NS), 34% (95% CI 8-53), and 60% (46-70) (P < 0.05).
      Rates of decline in GFR were 1.3 +/- 0.7, 1.2 +/- 0.7, and 1.0 +/- 0.8 ml. min(
      1). 1.73 m(-2) per month, respectively, during the initial 3 months of the study
      and 0.3 +/- 0.1, 0.3 +/- 0.1, and 0.4 +/- 0.1 ml. min(-1). 1.73 m(-2) per month
      in the remaining study period. One month after withdrawal of all antihypertensive
      medication, MABP remained unchanged in the placebo group, 105 +/- 2 mmHg, but
      increased significantly in the irbesartan groups, to 109 +/- 2 and 108 +/- 2
      mmHg, respectively. Compared with baseline, urinary albumin excretion rate was
      increased by 14% (-17 to 54) in the placebo group and by 11% (-26 to 65) in the
      irbesartan 150-mg group but was persistently reduced by 47% (24-73) in the
      irbesartan 300-mg group (P < 0.05). GFR levels increased to baseline values in
      the placebo group and approached initial levels in irbesartan groups.
      CONCLUSIONS: Persistent reduction of microalbuminuria after withdrawal of all
      antihypertensive treatment suggests that high-dose irbesartan treatment confers
      long-term renoprotective effects.

PMID- 14633818
TI  - Contribution of visceral adiposity to the exaggerated postprandial lipemia of men
      with impaired glucose tolerance.
AB  - OBJECTIVE: Impaired glucose tolerance (IGT) has been associated with alterations
      in numerous coronary heart disease risk factors, including postprandial
      hyperlipidemia. An excess visceral adipose tissue accumulation is also predictive
      of IGT and of an exaggerated postprandial lipemia. The objective of the present
      study was therefore to compare the respective contributions of visceral adipose
      tissue accumulation versus IGT with the variation in postprandial lipemia.
      RESEARCH DESIGN AND METHODS: Potential differences in postprandial triglyceride
      (TG)-rich lipoprotein (TRL) levels following a standardized breakfast with a high
      fat content were examined among men characterized by normal glucose tolerance
      (NGT) or IGT. Sixty-seven men were classified according to their glucose
      tolerance status (<7.8 mmol/l [NGT] or between 7.8 and 11.1 mmol/l [IGT] 2 h
      after a 75-g oral glucose test). RESULTS: Men with IGT showed the highest TRL-TG
      concentrations (P < 0.05) at the 4-, 6-, and 8-h time points compared with men
      with NGT. These higher postprandial TRL-TG levels among men with IGT were also
      accompanied by a greater postprandial TG total area under the incremental curve
      in all TRL fractions (large, medium, and small) (P < 0.05). Furthermore, subjects
      characterized by IGT had also the highest visceral adipose tissue accumulation (P
      < 0.009). When subgroups of IGT and NGT men were individually matched (n = 11)
      for similar visceral adipose tissue accumulation, no significant difference was
      found in postprandial responses of all TRL-TG fractions between the two groups.
      CONCLUSIONS: These results provide evidence that visceral adipose tissue
      accumulation is an important factor involved in the deterioration of postprandial
      lipemia noted among men with IGT.

PMID- 14633819
TI  - Insulin suppresses plasma concentration of vascular endothelial growth factor and
      matrix metalloproteinase-9.
AB  - OBJECTIVE: We recently demonstrated a potent anti-inflammatory and thus a
      potential antiatherogenic effect of insulin in human aortic endothelial cells and
      mononuclear cells at physiologically relevant concentrations. We have now further
      investigated the anti-inflammatory suppressive action of insulin on vascular
      endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9. VEGF and
      MMP-9 play a central regulatory role in angiogenesis, contribute to the
      pathogenesis of proliferative retinopathy, and have also been found to accelerate
      atherosclerosis. RESEARCH DESIGN AND METHODS: Insulin was infused (2 IU/h) in 5%
      dextrose (100 ml/h) and KCl (8 mmol/h) into 10 fasting, obese, nondiabetic
      subjects for 4 h. Subjects were also infused with 5% dextrose without insulin and
      with saline on two separate occasions. Blood samples were obtained at 0, 2, 4,
      and 6 h. RESULTS: Plasma insulin concentrations increased from a basal level of
      12.5 +/- 2.2 to 28.2 +/- 3.3 micro U/ml at 2 h and 24.4 +/- 3.7 micro U/ml at 4 h
      after insulin infusion. VEGF concentration decreased from 307.2 +/- 163.8 pg/ml
      (100%) at 0 h to 73.5 +/- 20.9% of the basal level at 2 h and 67.1 +/- 23.2% at
      4h. Plasma MMP-9 concentrations decreased from 375 +/- 196.3 ng/ml (100%) at 0 h
      to 83 +/- 22% of the basal level at 2 h and to 82 +/- 21% of the basal level at 4
      h (P < 0.05). Dextrose infusion alone did not change plasma VEGF concentration.
      However, plasma MMP-9 concentration increased significantly at 4 h following
      dextrose infusion alone (P < 0.05). Saline infusions without insulin caused no
      alteration in glucose, insulin, VEGF, or MMP-9. CONCLUSIONS: These observations
      may have implications for a potential antiretinopathic and antiatherosclerotic
      effect of insulin in the long term.

PMID- 14633820
TI  - Plasma adiponectin and endogenous glucose production in humans.
AB  - OBJECTIVE: High plasma adiponectin is associated with reduced risk of type 2
      diabetes, probably a consequence of its insulin-sensitizing properties. In vivo
      data in rodents suggest that the insulin-sensitization responsible for
      improvement of glycemia occurs in muscle and liver. Whereas associations of
      plasma adiponectin with muscle insulin sensitivity in humans have been examined,
      this has not been done for the liver. RESEARCH DESIGN AND METHODS: We therefore
      analyzed the relationship between fasting plasma adiponectin and basal endogenous
      glucose production [EGP]-basal) and insulin-suppressed EGP (EGP-insulin, isotope
      dilution technique) in 143 Pima Indians (94 with normal glucose tolerance, 36
      with impaired glucose tolerance, and 16 with type 2 diabetes). RESULTS: Fasting
      plasma adiponectin concentrations were negatively correlated with EGP-basal and
      EGP-insulin before (P = 0.006 and P < 0.0001, respectively) as well as after
      adjustment for age, sex, percent body fat, and insulin-stimulated whole-body
      glucose uptake (P = 0.007 and P = 0.0005, respectively). CONCLUSIONS: These
      findings are compatible with the hypothesis that adiponectin increases hepatic
      insulin sensitivity. Consistent with data in animals, adiponectin may have
      generalized insulin-sensitizing effects in humans.

PMID- 14633821
TI  - Diagnosing insulin resistance by simple quantitative methods in subjects with
      normal glucose metabolism.
AB  - OBJECTIVE: To identify a reliable yet simple indirect method for detection of
      insulin resistance (IR). RESEARCH DESIGN AND METHODS: A total of 65 subjects (44
      men and 21 women aged 30-60 years) were selected by a simple random sampling
      method. Inclusion criteria were voluntary participation from staff and hospital
      personnel, absence of abnormal glucose tolerance, and normal results of lipid
      profile and basic blood chemistry. A blood sample was taken after a 12-h
      overnight fast to determine plasma lipid, glucose, and insulin levels. An
      intravenous glucose tolerance test with administration of insulin after 20 min
      and extraction of multiple blood samples for glucose and insulin measurements and
      calculation of the minimal model approximation of the metabolism of glucose
      (MMAMG) S(i) value were performed. Three indirect indexes used to predict insulin
      sensitivity or IR were calculated, and metabolic syndrome was diagnosed using the
      Adult Treatment Panel III (ATP III) criteria. All results were correlated with
      those of the MMAMG. RESULTS: The 75th percentile value as the cutoff point to
      define IR corresponded with a fasting plasma glucose level of 12 mU/l, a
      homeostasis model assessment of 2.6, a 25th percentile for S(i) value of 21, and
      QUICKI (quantitative insulin sensitivity check index) and McAuley indexes of 0.33
      and 5.8, respectively. The S(i) index correlated (P < 0.001) with all the
      indirect indexes and parameters of the metabolic syndrome. CONCLUSIONS: When
      compared with the S(i) index, the most sensitive and specific indirect method was
      the score proposed by McAuley et al. (specificity 0.91, sensitivity 0.75, 9.2
      probability ratio of a positive test), followed by the existence of metabolic
      syndrome (specificity 0.91, sensitivity 0.66, 7.8 probability ratio of a positive
      test).

PMID- 14633822
TI  - Why can't we prevent type 1 diabetes?: maybe it's time to try a different
      combination.

PMID- 14633823
TI  - Lowering the criterion for impaired fasting glucose will not provide clinical
      benefit.

PMID- 14633824
TI  - Lowering the criterion for impaired fasting glucose is in order.

PMID- 14633825
TI  - Peripheral arterial disease in people with diabetes.

PMID- 14633826
TI  - Approaches to cardiovascular disease and its treatment.

PMID- 14633827
TI  - Aspirin for primary prevention of cardiovascular events in diabetes.

PMID- 14633828
TI  - Nonalcoholic fatty liver disease in Saudi type 2 diabetic subjects attending a
      medical outpatient clinic: prevalence and general characteristics.

PMID- 14633829
TI  - Prevalence and risk factors of diabetic foot problems in Taiwan: a cross
      sectional survey of non-type 1 diabetic patients from a nationally representative
      sample.

PMID- 14633830
TI  - Prospective audit of the introduction of insulin glargine (lantus) into clinical
      practice in type 1 diabetic patients.

PMID- 14633831
TI  - Self-blood glucose monitoring practices: do patients know and act on their
      target?

PMID- 14633832
TI  - The cutoff value of fasting plasma glucose to differentiate frequencies of
      cardiovascular risk factors in a Korean population.

PMID- 14633833
TI  - Safety issues on metformin use.

PMID- 14633834
TI  - High prevalence of peripheral arterial disease but low antiplatelet treatment
      rates in elderly primary care patients with diabetes.

PMID- 14633835
TI  - Patient and provider congruence.

PMID- 14633836
TI  - Maturity-onset diabetes of the young (MODY) mutation in type 2 diabetes and
      latent autoimmune diabetes of the adult.

PMID- 14633837
TI  - It can be done.

PMID- 14633838
TI  - Glimepiride and serum adiponectin level in type 2 diabetic subjects: response to
      Nagasaka et al.

PMID- 14633839
TI  - Comparison of repaglinide and nateglinide in combination with metformin: response
      to Raskin et al.

PMID- 14633842
TI  - Meta-analysis of low-glycemic index diets in the management of diabetes: response
      to Franz.

PMID- 14633844
TI  - Meta-analysis of low-glycemic index diets in the management of diabetes: response
      to Franz.

PMID- 14633845
TI  - Microvascular complications of impaired glucose tolerance.
AB  - Impaired glucose tolerance (IGT) serves as a marker for the state of insulin
      resistance and predicts both large- and small-vessel vascular complications,
      independent of a patient's progression to diabetes. Patients with IGT are at
      significantly increased risk for death and morbidity due to myocardial
      infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of
      cardiovascular morbidity than impaired fasting glucose, probably because it is a
      better surrogate for the state of insulin resistance. IGT is also independently
      associated with traditional microvascular complications of diabetes, including
      retinopathy, renal disease, and polyneuropathy, which are the topics of this
      review. Inhibition of nitric oxide-mediated vasodilation, endothelial injury due
      to increased release of free fatty acids and adipocytokines from adipocytes, and
      direct metabolic injury of endothelial and end-organ cells contribute to vascular
      complications. Early detection of IGT allows intensive diet and exercise
      modification, which has proven significantly more effective than drug therapy in
      normalizing postprandial glucose and inhibiting progression to diabetes. To what
      degree intervention will limit recognized complications is not known.

PMID- 14633846
TI  - Endurance training in humans leads to fiber type-specific increases in levels of
      peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome
      proliferator-activated receptor-alpha in skeletal muscle.
AB  - The peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PGC-1)
      can induce mitochondria biogenesis and has been implicated in the development of
      oxidative type I muscle fibers. The PPAR isoforms alpha, beta/delta, and gamma
      control the transcription of genes involved in fatty acid and glucose metabolism.
      As endurance training increases skeletal muscle mitochondria and type I fiber
      content and fatty acid oxidative capacity, our aim was to determine whether these
      increases could be mediated by possible effects on PGC-1 or PPAR-alpha, 
      beta/delta, and -gamma. Seven healthy men performed 6 weeks of endurance training
      and the expression levels of PGC-1 and PPAR-alpha, -beta/delta, and -gamma mRNA
      as well as the fiber type distribution of the PGC-1 and PPAR-alpha proteins were
      measured in biopsies from their vastus lateralis muscle. PGC-1 and PPAR-alpha
      mRNA expression increased by 2.7- and 2.2-fold (P < 0.01), respectively, after
      endurance training. PGC-1 expression was 2.2- and 6-fold greater in the type IIa
      than in the type I and IIx fibers, respectively. It increased by 2.8-fold in the
      type IIa fibers and by 1.5-fold in both the type I and IIx fibers after endurance
      training (P < 0.015). PPAR-alpha was 1.9-fold greater in type I than in the II
      fibers and increased by 3.0-fold and 1.5-fold in these respective fibers after
      endurance training (P < 0.001). The increases in PGC-1 and PPAR-alpha levels
      reported in this study may play an important role in the changes in muscle
      mitochondria content, oxidative phenotype, and sensitivity to insulin known to be
      induced by endurance training.

PMID- 14633847
TI  - Elevation of free fatty acids induces inflammation and impairs vascular
      reactivity in healthy subjects.
AB  - To test the possible acute proinflammatory effects of fatty acids, we induced an
      increase in plasma free fatty acid (FFA) concentrations after a lipid and heparin
      infusion for 4 h in 10 healthy subjects. We determined the nuclear factor-kappaB
      (NF-kappaB) binding activity in mononuclear cells (MNCs), the p65 subunit of NF
      kappaB, reactive oxygen species (ROS) generation by MNC, and polymorphonuclear
      leukocytes (PMN). Brachial artery reactivity, using postischemic flow-mediated
      dilation, was also measured. NF-kappaB binding activity in the MNC nuclear
      extracts increased to 163 +/- 17% and 144 +/- 14% as compared with basal levels
      at 2 and 4 h (P < 0.005) and remained elevated (P < 0.05) at 6 h (2 h after
      cessation of lipid infusion). NF-kappaB p65 subunit protein expression in MNC
      homogenates also increased at 2, 4, and 6 h (P < 0.05). ROS generation by PMNs
      increased significantly at 2 and 4 h (P < 0.005), whereas that by MNCs increased
      at 4 h (P < 0.05). Plasma macrophage migration inhibitory factor increased at 2
      (P < 0.05) and 4 h (P < 0.005), respectively, and declined to baseline at 6 h.
      The postischemic flow-mediated dilation of brachial artery decreased from 6.3 +/-
      1.1% at baseline to 4.3 +/- 1.9% and 2.7 +/- 2.1% (P < 0.01) at 2, 4, and 6 h,
      respectively. We conclude that an increase in FFA concentration induces oxidative
      stress and has a proinflammatory effect; it also impairs postischemic flow
      mediated vasodilation of the brachial artery.

PMID- 14633848
TI  - A mammalian protein homologous to fructosamine-3-kinase is a ketosamine-3-kinase
      acting on psicosamines and ribulosamines but not on fructosamines.
AB  - Fructosamine-3-kinase (FN3K) is an enzyme that appears to be responsible for the
      removal of fructosamines from proteins. In this study, we report the sequence of
      human and mouse cDNAs encoding proteins sharing 65% sequence identity with FN3K.
      The genes encoding FN3K and FN3K-related protein (FN3K-RP) are present next to
      each other on human chromosome 17q25, and they both have a similar 6-exon
      structure. Northern blots of mouse tissues RNAs indicate a high level of
      expression of both genes in bone marrow, brain, kidneys, and spleen. Human FN3K
      RP was transfected in human embryonic kidney (HEK) cells, and the expressed
      protein was partially purified by chromatography on Blue Sepharose. Unlike FN3K,
      FN3K-RP did not phosphorylate fructoselysine, 1-deoxy-1-morpholino-fructose, or
      lysozyme glycated with glucose. In a more systematic screening for potential
      substrates for FN3K-RP, we found, however, that both enzymes phosphorylated
      ketosamines with a D-configuration in C3 (psicoselysine, 1-deoxy-1-morpholino
      psicose, 1-deoxy-1-morpholino-ribulose, lysozyme glycated with allose-the C3
      epimer of glucose, or with ribose). Tandem mass spectrometry and nuclear magnetic
      resonance analysis of the product of phosphorylation of 1-deoxy-1-morpholino
      psicose by FN3K-RP indicated that this enzyme phosphorylates the third carbon of
      the sugar moiety. These results indicate that FN3K-RP is a ketosamine-3-kinase
      (ketosamine-3-kinase 2). This enzyme presumably plays a role in freeing proteins
      from ribulosamines or psicosamines, which might arise in a several step process,
      from the reaction of amines with glucose and/or glycolytic intermediates. This
      role is shared by fructosamine-3-kinase (ketosamine-3-kinase 1), which has, in
      addition, the unique capacity to phosphorylate fructosamines.

PMID- 14633849
TI  - Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic
      transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase.
AB  - Oxidative stress is induced in pancreatic beta-cells under diabetic conditions
      and causes beta-cell dysfunction. Antioxidant treatment of diabetic animals leads
      to recovery of insulin biosynthesis and increases the expression of its
      controlling transcription factor, pancreatic duodenal homeobox-1 (PDX-1), in
      pancreatic beta-cells. Here, we show that PDX-1 is translocated from the nuclei
      to the cytoplasm of pancreatic beta-cells in response to oxidative stress. When
      oxidative stress was charged upon beta-cell-derived HIT-T15 cells, both
      endogenous PDX-1 and exogenously introduced green fluorescent protein-tagged PDX
      1 moved from the nuclei to the cytoplasm. The addition of a dominant negative
      form of c-Jun NH(2)-terminal kinase (JNK) inhibited oxidative stress-induced PDX
      1 translocation, suggesting an essential role of JNK in mediating this
      phenomenon. Whereas the nuclear localization signal (NLS) in PDX-1 was not
      affected by oxidative stress, leptomycin B, a specific inhibitor of the classical
      leucine-rich nuclear export signal (NES), inhibited nucleo-cytoplasmic
      translocation of PDX-1 induced by oxidative stress. Moreover, we identified an
      NES at position 82-94 of the mouse PDX-1 protein. Thus, our present results
      revealed a novel mechanism that negatively regulates PDX-1 function. The
      identification of the NES, which overrides the function of the NLS in an
      oxidative stress-responsive, JNK-dependent manner, supports the complicated
      regulation of PDX-1 function in vivo and may further the understanding of beta
      cell pathophysiology in diabetes.

PMID- 14633850
TI  - Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and
      hypertriglyceridemia with sterol regulatory element binding protein involvement.
AB  - Akt is critical in insulin-induced metabolism of glucose and lipids. To
      investigate functions induced by hepatic Akt activation, a constitutively active
      Akt, NH(2)-terminally myristoylation signal-attached Akt (myr-Akt), was
      overexpressed in the liver by injecting its adenovirus into mice. Hepatic myr-Akt
      overexpression resulted in a markedly hypoglycemic, hypoinsulinemic, and
      hypertriglyceridemic phenotype with fatty liver and hepatomegaly. To elucidate
      the sterol regulatory element binding protein (SREBP)-1c contribution to these
      phenotypic features, myr-Akt adenovirus was injected into SREBP-1 knockout mice.
      myr-Akt overexpression induced hypoglycemia and hepatomegaly with triglyceride
      accumulation in SREBP-1 knockout mice to a degree similar to that in normal mice,
      whereas myr-Akt-induced hypertriglyceridemia in knockout mice was milder than
      that in normal mice. The myr-Akt-induced changes in glucokinase,
      phosphofructokinase, glucose-6-phosphatase, and PEPCK expressions were not
      affected by knocking out SREBP-1, whereas stearoyl-CoA desaturase 1 induction was
      completely inhibited in knockout mice. Constitutively active SREBP-1
      overexpressing mice had fatty livers without hepatomegaly, hypoglycemia, or
      hypertriglyceridemia. Hepatic acetyl-CoA carboxylase, fatty acid synthase,
      stearoyl-CoA desaturase 1, and glucose-6-phosphate dehydrogenase expressions were
      significantly increased by overexpressing SREBP-1, whereas glucokinase, phospho
      fructokinase, glucose-6-phosphatase, and PEPCK expressions were not or only
      slightly affected. Thus, SREBP-1 is not absolutely necessary for the hepatic Akt
      mediated hypoglycemic effect. In contrast, myr-Akt-induced hypertriglyceridemia
      and hepatic triglyceride accumulation are mediated by both Akt-induced SREBP-1
      expression and a mechanism involving fatty acid synthesis independent of SREBP-1.

PMID- 14633851
TI  - Agouti expression in human adipose tissue: functional consequences and increased
      expression in type 2 diabetes.
AB  - It is well recognized that the agouti/melanocortin system is an important
      regulator of body weight homeostasis. Given that agouti is expressed in human
      adipose tissue and that the ectopic expression of agouti in adipose tissue
      results in moderately obese mice, the link between agouti expression in human
      adipose tissue and obesity/type 2 diabetes was investigated. Although there was
      no apparent relationship between agouti mRNA levels and BMI, agouti mRNA levels
      were significantly elevated in subjects with type 2 diabetes. The regulation of
      agouti in cultured human adipocytes revealed that insulin did not regulate agouti
      mRNA, whereas dexamethasone treatment potently increased the levels of agouti
      mRNA. Experiments with cultured human preadipocytes and with cells obtained from
      transgenic mice that overexpress agouti demonstrated that melanocortin receptor
      (MCR) signaling in adipose tissue can regulate both preadipocyte proliferation
      and differentiation. Taken together, these results reveal that agouti can
      regulate adipogenesis at several levels and suggest that there are functional
      consequences of elevated agouti levels in human adipose tissue. The influence of
      MCR signaling on adipogenesis combined with the well-established role of MCR
      signaling in the hypothalamus suggest that adipogenesis is coordinately regulated
      with food intake and energy expenditure.

PMID- 14633852
TI  - Insulin is required for prandial ghrelin suppression in humans.
AB  - Accumulating evidence indicates that ghrelin plays a role in regulating food
      intake and energy homeostasis. In normal subjects, circulating ghrelin
      concentrations decrease after meal ingestion and increase progressively before
      meals. At present, it is not clear whether nutrients suppress the plasma ghrelin
      concentration directly or indirectly by stimulating insulin secretion. To test
      the hypothesis that insulin regulates postprandial plasma ghrelin concentrations
      in humans, we compared the effects of meal ingestion on plasma ghrelin levels in
      six C-peptide-negative subjects with type 1 diabetes and in six healthy subjects
      matched for age, sex, and BMI. Diabetic subjects were studied during absence of
      insulin (insulin withdrawal study), with intravenous infusion of basal insulin
      (basal insulin study) and subcutaneous administration of a prandial insulin dose
      (prandial insulin study). Meal intake suppressed plasma ghrelin concentrations
      (nadir at 105 min) by 32 +/- 4% in normal control subjects, 57 +/- 3% in diabetic
      patients during the prandial insulin study (P < 0.002 vs. control subjects), and
      38 +/- 8% during basal insulin study (P = 0.0016 vs. hyperinsulinemia; P = NS vs.
      control subjects) but did not have any effect in the insulin withdrawal study (P
      < 0.001 vs. other studies). In conclusion, 1). insulin is essential for meal
      induced plasma ghrelin suppression, 2). basal insulin availability is sufficient
      for postprandial ghrelin suppression in type 1 diabetic subjects, and 3). lack of
      meal-induced ghrelin suppression caused by severe insulin deficiency may explain
      hyperphagia of uncontrolled type 1 diabetic subjects.

PMID- 14633853
TI  - Adrenalectomy alters the sensitivity of the central nervous system melanocortin
      system.
AB  - Removal of adrenal steroids by adrenalectomy (ADX) reduces food intake and body
      weight in rodents and prevents excessive weight gain in many genetic and dietary
      models of obesity. Thus, glucocorticoids appear to play a key role to promote
      positive energy balance in normal and pathological conditions. By comparison,
      central nervous system melanocortin signaling provides critical inhibitory tone
      to regulate energy balance. The present experiments sought to test whether
      glucocorticoids influence energy balance by altering the sensitivity to
      melanocortin receptor ligands. Because melanocortin-producing neurons are
      hypothesized to be downstream of leptin in a key weight-reducing circuit, we
      tested rats for their sensitivity to leptin and confirmed reports that the
      hypophagic response to third ventricular (i3vt) leptin is increased in ADX rats
      and is normalized by glucocorticoid replacement. Next we tested rats for their
      sensitivity to the melanocortin agonist melanotan II and found that, as for
      leptin, ADX enhanced the hypophagic response via a glucocorticoid-dependent
      mechanism. The central nervous system melanocortin system is unique in that it
      includes the endogenous melanocortin receptor antagonist, AgRP. The orexigenic
      effect of i3vt AgRP was absent in ADX rats and restored by glucocorticoid
      replacement. We conclude that the potent weight-reducing effects of ADX likely
      involve heightened responsiveness to melanocortin receptor stimulation.

PMID- 14633854
TI  - Brain death significantly reduces isolated pancreatic islet yields and
      functionality in vitro and in vivo after transplantation in rats.
AB  - Although approximately 1 million islets exist in the adult human pancreas,
      current pancreas preservation and islet isolation techniques recover <50%.
      Presently, cadaveric donors remain the sole source of pancreatic tissue for
      transplantation. Brain death is characterized by activation of proinflammatory
      cytokines and organ injury during preservation and reperfusion. In this study, we
      assessed the effects of brain death on islet isolation yields and functionality.
      Brain death was induced in male 250- to 350-g Lewis rats by inflation of a
      Fogarty catheter placed intracranially. The rats were mechanically ventilated for
      2, 4, and 6 h before removal of the pancreas (n = 6). In controls, the catheter
      was not inflated (n = 6). Shortly after brain death induction, a significant
      increase in serum tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)
      1beta, and IL-6 was demonstrated in a time-dependent manner. Upregulation of TNF
      alpha, IL-1beta, and IL-6 mRNA was noted in the pancreas. Brain death donors
      presented lower insulin release after glucose stimulation assessed by in situ
      perfusion of the pancreas. Islet recovery was reduced in brain death donors
      compared with controls (at 6 h 602.3 +/- 233.4 vs. 1,792.5 +/- 325.4 islet
      equivalents, respectively; P < 0.05). Islet viability assessed in dissociated
      islet cells and in intact cultured islets was reduced in islets recovered from
      brain death donors, an effect associated with higher nuclear activities of NF
      kappaB p50, c-Jun, and ATF-2. Islet functionality evaluated in vitro by static
      incubation and in vivo after intraportal transplantation in syngeneic
      streptozotocin-induced diabetic rats was significantly reduced in preparations
      obtained from brain death donors. In conclusion, brain death significantly
      reduced islet yields and functionality. These observations may lead to strategies
      to reduce the effects of brain death on pancreatic islets and improve the results
      in clinical transplantation.

PMID- 14633855
TI  - On-line monitoring of apoptosis in insulin-secreting cells.
AB  - Apoptosis was monitored in intact insulin-producing cells both with
      microfluorometry and with two-photon laser scanning microscopy (TPLSM), using a
      fluorescent protein based on fluorescence resonance energy transfer (FRET). TPLSM
      offers three-dimensional spatial information that can be obtained relatively deep
      in tissues. This provides a potential for future in vivo studies of apoptosis.
      The cells expressed a fluorescent protein (C-DEVD-Y) consisting of two
      fluorophores, enhanced cyan fluorescent protein (ECFP) and enhanced yellow
      fluorescent protein (EYFP), linked by the amino acid sequence DEVD selectively
      cleaved by caspase-3-like proteases. FRET between ECFP and EYFP in C-DEVD-Y could
      therefore be monitored on-line as a sensor of caspase-3 activation. The relevance
      of using caspase-3 activation to indicate beta-cell apoptosis was demonstrated by
      inhibiting caspase-3-like proteases with Z-DEVD-fmk and thereby showing that
      caspase-3 activation was needed for high-glucose-and cytokine-induced apoptosis
      in the beta-cell and for staurosporine-induced apoptosis in RINm5F cells. In
      intact RINm5F cells expressing C-DEVD-Y and in MIN6 cells expressing the variant
      C-DEVD-Y2, FRET was lost at 155 +/- 23 min (n = 9) and 257 +/- 59 min (n = 4;
      mean +/- SE) after activation of apoptosis with staurosporine (6 micromol/l),
      showing that this method worked in insulin-producing cells.

PMID- 14633856
TI  - Gestational diabetes induces placental genes for chronic stress and inflammatory
      pathways.
AB  - A physiological state of insulin resistance is required to preferentially direct
      maternal nutrients toward the feto-placental unit, allowing adequate growth of
      the fetus. When women develop gestational diabetes mellitus (GDM), insulin
      resistance is more severe and disrupts the intrauterine milieu, resulting in
      accelerated fetal development with increased risk of macrosomia. As a natural
      interface between mother and fetus, the placenta is the obligatory target of such
      environmental changes. However, the molecular basis for the imbalance that leads
      to fetal, neonatal, and adult metabolic compromises is not well understood. We
      report that GDM elicits major changes in the expression profile of placental
      genes with a prominent increase in markers and mediators of inflammation. Within
      the 435 transcripts reproducibly modified, genes for stress-activated and
      inflammatory responses represented the largest functional cluster (18.5% of
      regulated genes). Upregulation of interleukins, leptin, and tumor necrosis factor
      alpha receptors and their downstream molecular adaptors indicated an activation
      of pathways recruiting stress-activated protein/c-Jun NH(2)-terminal kinases.
      Transcriptional activation of extracellular matrix components and angiogenic
      activators pointed to a major structural reorganization of the placenta. Thus,
      placental transcriptome emerges as a primary target of the altered environment of
      diabetic pregnancy. The genes identified provide the basis to elucidate links
      between inflammatory pathways and GDM-associated insulin resistance.

PMID- 14633857
TI  - Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis
      and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial
      cells.
AB  - Vascular insufficiency and retinal ischemia precede many proliferative
      retinopathies and stimulate secretion of various vasoactive growth factors,
      including vascular endothelial growth factor (VEGF) and placenta growth factor
      (PlGF). It is unclear, however, how PlGF, which is elevated in proliferative
      diabetic retinopathy and is a VEGF homolog that binds only to VEGF receptor
      (VEGFR)-1, promotes pathological angiogenesis. When primary microvascular
      endothelial cells were grown on collagen gels, PlGF-containing ligands
      upregulated Bcl-2 expression and stimulated the formation of capillary-like tube
      networks that were retained for up to 14 days in culture. The inhibition of VEGFR
      1 results in a dramatic decrease in the number of capillary connections,
      indicating that VEGFR-1 ligands promote branching angiogenesis. In contrast, VEGF
      induced tube formations and Bcl-2 expression were significantly decreased at the
      end of this period. Flow cytometry analysis of annexin-V/propidium iodide-stained
      cells revealed that PlGF and PlGF/VEGF heterodimer inhibited apoptosis in serum
      deprived endothelial cells. These two growth factors stimulated a survival
      signaling pathway phosphatidylinositol 3-kinase (PI3K), as identified by
      increased Akt phosphorylation and because blocking PI3K signalling by adenovirus
      mediated overexpression of wild-type phosphatase and tensin homolog on chromosome
      10 (PTEN) disrupted angiogenesis and decreased Bcl-2 expression by PlGF and
      PlGF/VEGF heterodimer, whereas a dominant-negative PTEN mutant enhanced
      endothelial sprout formation and Bcl-2 expression. Together, these findings
      indicate that PlGF-containing ligands contribute to pathological angiogenesis by
      prolonging cell survival signals and maintaining vascular networks.

PMID- 14633858
TI  - Nephrinuria in diabetic nephropathy of type 1 diabetes.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease. Because
      early diagnosis and treatment may prevent the complication, new tools for an
      early detection are needed. One of the key components of the glomerular
      filtration slit spanning between neighboring podocytes is nephrin. Its expression
      is altered in experimental models of diabetes and also in various human
      proteinuric diseases, including diabetes. We studied whether type 1 diabetic
      patients with or without nephropathy exhibit immunoreactive nephrin in the urine,
      reflecting early damage of the filtration barrier. Diabetic patients with
      normoalbuminuria (n = 40), with microalbuminuria (n = 41), and with
      macroalbuminuria (n = 39) and patients previously normoalbuminuric but now
      testing positive for microalbuminuria (newMicro, n = 39) were screened for
      nephrinuria with Western blotting using two affinity-purified anti-nephrin
      antibodies. Nondiabetic healthy subjects (n = 29) were also studied. Nephrinuria
      was present in 30% of normoalbuminuric, 17% of microalbuminuric, 28% of
      macroalbuminuric, and 28% of newMicro patients. Of female patients, 35% were
      nephrinuric compared with only 19% of male patients (P = 0.02). None of the
      control subjects was nephrinuric. In conclusion, glomerular filtration barrier
      may be affected in one-third of diabetic patients manifesting as early
      nephrinuria. Nephrinuria may have prognostic value and become a marker of
      susceptibility for kidney complications in diabetes.

PMID- 14633859
TI  - Connective tissue growth factor and igf-I are produced by human renal fibroblasts
      and cooperate in the induction of collagen production by high glucose.
AB  - Tubulointerstitial fibrosis is an important component in the development of
      diabetic nephropathy. Various renal cell types, including fibroblasts, contribute
      to the excessive matrix deposition in the kidney. Although transforming growth
      factor-beta (TGF-beta) has been thought to play a major role during fibrosis,
      other growth factors are also involved. Here we examined the effects of
      connective tissue growth factor (CTGF) and IGF-I on collagen type I and III
      production by human renal fibroblasts and their involvement in glucose-induced
      matrix accumulation. We have demonstrated that both CTGF and IGF-I expressions
      were increased in renal fibroblasts under hyperglycemic conditions, also in the
      absence of TGF-beta signaling. Although CTGF alone had no effect on collagen
      secretion, combined stimulation with IGF-I enhanced collagen accumulation.
      Furthermore, IGF-I also had a synergistic effect with glucose on the induction of
      collagens. Moreover, we observed a partial inhibition in glucose-induced collagen
      secretion with neutralizing anti-CTGF antibodies, thereby demonstrating for the
      first time the involvement of endogenous CTGF in glucose-induced effects in human
      renal fibroblasts. Therefore, the cooperation between CTGF and IGF-I might be
      involved in glucose-induced matrix accumulation in tubulointerstitial fibrosis
      and might contribute to the pathogenesis of diabetic nephropathy.

PMID- 14633860
TI  - Autosomal-dominant mode of inheritance of a melanocortin-4 receptor mutation in a
      patient with severe early-onset obesity is due to a dominant-negative effect
      caused by receptor dimerization.
AB  - Mutations in the melanocortin-4 receptor (MC4R) gene are the most frequent
      monogenic causes of severe obesity. Most mutations have been described as
      heterozygous with loss of function, suggesting that haploinsufficiency is the
      most likely mechanism of dominant inheritance. We detected a heterozygous
      mutation, D90N, in a patient with severe early-onset obesity. Functional
      characterization of the mutant receptor revealed normal cell-surface expression
      and binding properties but loss of signal transduction activity. In coexpression
      studies of wild-type (WT)-MC4R and D90N, the mutant receptor had a dominant
      negative effect on WT-receptor function. Further investigation of this effect
      with sandwich enzyme-linked immunosorbent assays and fluorescence resonance
      energy transfer studies showed that the WT-MC4R and the D90N mutant form
      homodimers and heterodimers. We hypothesize that the dominant-negative effect of
      the D90N mutation is caused by a functionally altered WT-MC4R/D90N receptor
      heterodimer. These findings necessitate the reinvestigation of other heterozygous
      MC4R missense mutations to discriminate between haploinsufficiency and a dominant
      negative effect. The finding of receptor dimerization highlights a more complex
      hypothalamic signaling network governing the regulation of body weight.

PMID- 14633861
TI  - Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear
      factor-1alpha: haploinsufficiency is associated with reduced serum apolipoprotein
      M levels.
AB  - Hepatocyte nuclear factor-1a (HNF-1alpha) is a transcription factor that plays an
      important role in regulation of gene expression in pancreatic beta-cells,
      intestine, kidney, and liver. Heterozygous mutations in the HNF-1alpha gene are
      responsible for maturity-onset diabetes of the young (MODY3), which is
      characterized by pancreatic beta-cell-deficient insulin secretion. HNF-1alpha is
      a major transcriptional regulator of many genes expressed in the liver. However,
      no liver defect has been identified in individuals with HNF-1alpha mutations. In
      this study, we show that Hnf-1alpha is a potent transcriptional activator of the
      gene encoding apolipoprotein M (apoM), a lipoprotein that is associated with the
      HDL particle. Mutant Hnf-1alpha(-/-) mice completely lack expression of apoM in
      the liver and the kidney. Serum apoM levels in Hnf-1alpha(+/-) mice are reduced
      approximately 50% compared with wild-type animals and are absent in the HDL and
      HDLc fractions of Hnf-1alpha(-/-). We analyzed the apoM promoter and identified a
      conserved HNF-1 binding site. We show that Hnf-1alpha is a potent activator of
      the apoM promoter, that a specific mutation in the HNF-1 binding site abolished
      transcriptional activation of the apoM gene, and that Hnf-1alpha protein can bind
      to the Hnf-1 binding site of the apoM promoter in vitro. To investigate whether
      patients with mutations in HNF-1alpha mutations (MODY3) have reduced serum apoM
      levels, we measured apoM levels in the serum of nine HNF-1alpha/MODY3 patients,
      nine normal matched control subjects (HNF-1alpha(+/+)), and nine HNF-4alpha/MODY1
      subjects. Serum levels of apoM were decreased in HNF-1alpha/MODY3 subjects when
      compared with control subjects (P < 0.02) as well as with HNF-4alpha/MODY1
      subjects, indicating that HNF-1alpha haploinsufficiency rather than hyperglycemia
      is the primary cause of decreased serum apoM protein concentrations. This study
      demonstrates that HNF-1alpha is required for apoM expression in vivo and that
      heterozygous HNF-1alpha mutations lead to an HNF-1alpha-dependent impairment of
      apoM expression. ApoM levels may be a useful serum marker for the identification
      of MODY3 patients.

PMID- 14633862
TI  - The human MC4R promoter: characterization and role in obesity.
AB  - Heterozygous mutations in the coding sequence of the serpentine melanocortin 4
      receptor (MC4R) are the most frequent genetic cause of severe human obesity.
      Since haploinsufficiency has been proposed as a causal mechanism of obesity
      associated with these mutations, reduction in gene transcription caused by
      mutations in the transcriptionally essential regions of the MC4R promoter may
      also be a cause of severe obesity in humans. To test this hypothesis we defined
      the minimal promoter region of the human MC4R and evaluated the extent of genetic
      variation in this region compared with the coding region in two cohorts of
      severely obese subjects. 5'RACE followed by functional promoter analysis in
      multiple cell lines indicates that an 80-bp region is essential for the
      transcriptional activity of the MC4R promoter. Systematic screening of 431 obese
      children and adults for mutations in the coding sequence and the minimal core
      promoter of MC4R reveals that genetic variation in the transcriptionally
      essential region of the MC4R promoter is not a significant cause of severe
      obesity in humans.

PMID- 14633863
TI  - A genome-wide search for genes involved in type 2 diabetes in a recently
      genetically isolated population from the Netherlands.
AB  - Multiple genes, interacting with the environment, contribute to the
      susceptibility to type 2 diabetes. We performed a genome-wide search to localize
      type 2 diabetes susceptibility genes in a recently genetically isolated
      population in the Netherlands. We identified 79 nuclear families with type 2
      diabetes who were related within 13 generations and performed a 770-marker genome
      wide scan search for shared founder alleles. Twenty-six markers yielded a
      logarithm of odds (LOD) score >0.59 (nominal P < 0.05), of which 7 reached LOD
      scores >1.17 (nominal P < 0.01). The strongest evidence for a type 2 diabetes
      locus was at marker D18S63 on chromosome 18p (LOD 2.3, P = 0.0006). This region
      was investigated further using additional markers. For one of these markers
      (D18S1105), we found a significant association with type 2 diabetes (odds ratio
      6.7 [95% CI 1.5-30.7], P = 0.005 for the 97-bp allele, assuming a dominant
      model), which increased when limiting the analysis to patients with high BMI
      (12.25 [2.1-71], P = 0.003). A locus on chromosome 18p in patients with high BMI
      was suggested earlier by Parker et al. Our study is the first to confirm this
      locus.

PMID- 14633864
TI  - The role of insulin receptor substrate-1 gene (IRS1) in type 2 diabetes in Pima
      Indians.
AB  - The insulin receptor substrate-1 (IRS1) is a critical element in insulin
      signaling pathways, and mutations in the IRS1 gene have been reported to have a
      role in determining susceptibility to traits related to type 2 diabetes. In gene
      expression studies of tissue biopsies from nondiabetic Pima Indians, IRS1 mRNA
      levels were reduced in adipocytes from obese subjects compared with lean
      subjects, and IRS1 mRNA levels were also reduced in skeletal muscle from insulin
      resistant subjects compared with insulin-sensitive subjects (all P < 0.05). Based
      on these expression differences and the known physiologic role of IRS1, this gene
      was investigated as a candidate gene for susceptibility to type 2 diabetes in
      Pima Indians, a population with an extremely high incidence and prevalence of
      type 2 diabetes. Thirteen variants were identified, and among these variants,
      several were in complete linkage disequilibrium. Four genotypically unique
      variants were further genotyped in 937 DNA samples from full-heritage Pima
      Indians. Three of the variants were modestly associated with type 2 diabetes (P <
      0.05), one of which was additionally associated with 2-h plasma insulin and
      glucose as well as insulin action at physiologic and maximally stimulating
      insulin concentrations (all P < 0.05). The association of variants in IRS1 with
      type 2 diabetes and type 2 diabetes-related phenotypes and the differential
      expression of IRS1 in adipocytes and skeletal muscle suggest a role of this gene
      in the pathogenesis of type 2 diabetes in Pima Indians.

PMID- 14633865
TI  - The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala
      polymorphism is associated with decreased risk of diabetic nephropathy in
      patients with type 2 diabetes.
AB  - The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala
      polymorphism has been associated with a decreased risk of type 2 diabetes and a
      lower albumin excretion rate (AER) in patients with established diabetes. We
      performed a case-control study aiming to evaluate the association between the
      Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104
      type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on
      dialysis and 26 with proteinuria [AER >or=200 microg/min] and serum creatinine
      >or=2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 microg/min) with known
      diabetes duration >or=10 years (control subjects). The genotypic distribution of
      the PPARgamma2 Pro12Ala polymorphism in these diabetic patients was in Hardy
      Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala
      carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case
      subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala
      carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele
      were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1%
      males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 +/- 10 vs. 61 +/
      10 years), known diabetes duration (17 +/- 7 vs. 16 +/- 7 years), BMI (27 +/- 4
      vs. 28 +/- 5 kg/m(2)), fasting plasma glucose (184 +/- 81 vs. 176 +/- 72 mg/dl),
      HbA(1c) (6.7 +/- 2.3 vs. 6.9 +/- 2.4%; high-performance liquid chromatography
      reference range: 2.7-4.3%), and systolic (145 +/- 27 vs. 0.144 +/- 24 mmHg) or
      diastolic (87 +/- 14 vs. 85 +/- 14 mmHg) blood pressure, respectively. In
      conclusion, the presence of the Ala allele may confer protection from diabetic
      nephropathy in patients with type 2 diabetes.

PMID- 14633866
TI  - Circulating forms of parathyroid hormone: peeling back the onion.

PMID- 14633867
TI  - Quantitative analysis and prognostic implication of SARS coronavirus RNA in the
      plasma and serum of patients with severe acute respiratory syndrome.
AB  - BACKGROUND: The availability of an early diagnostic tool for severe acute
      respiratory syndrome (SARS) would have major public health implications. We
      investigated whether the SARS coronavirus (SARS-CoV) can be detected in serum and
      plasma samples during the early stages of SARS and studied the potential
      prognostic implications of such an approach. METHODS: We developed two real-time
      quantitative reverse transcription-PCR (RT-PCR) assays, one for the polymerase
      and the other for the nucleocapsid region of the virus genome, for measuring the
      concentration of SARS-CoV RNA in serum/plasma samples from SARS patients. Plasma
      samples were obtained from 12 confirmed SARS patients on the day of hospital
      admission, as well as on days 7 and 14 after fever onset. Serum samples were also
      obtained from 23 confirmed SARS patients on the day of hospital admission, 11 of
      whom subsequently required intensive care. Viral RNA was extracted from the
      plasma/serum samples. The extracted RNA was subjected to analysis by the RT-PCR
      assays. RESULTS: The RT-PCR system for the polymerase region detected SARS-CoV
      RNA in 50% of plasma and 78% of serum samples from SARS patients during the first
      week of illness. The detection rates for plasma dropped to 25% at day 14 after
      fever onset. The median serum SARS-CoV concentrations in patients who required
      and did not require intensive care unit admission during the course of
      hospitalization were 5800 and 140 copies/mL, respectively (Mann-Whitney test, P
      <0.005). These data were confirmed by the RT-PCR system for the nucleocapsid
      region, which showed an even higher detection rate of 87%. The correlation
      between the results obtained by the two RT-PCR systems was high (Pearson
      correlation analysis, r = 0.998; P <0.001). CONCLUSION: Plasma/serum SARS-CoV
      quantification represents a potentially useful early diagnostic and prognostic
      tool for SARS.

PMID- 14633868
TI  - Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2
      genes by denaturing HPLC analysis of individuals with biochemical indications of
      iron overload.
AB  - BACKGROUND: Hereditary hemochromatosis is a recessive disorder characterized by
      iron accumulation in parenchymal cells, followed by organ damage and failure. The
      disorder is mainly attributable to the C282Y and H63D mutations in the HFE gene,
      but additional mutations in the HFE, transferrin receptor 2 (TfR2), and hepcidin
      genes have been reported. The copresence of mutations in different genes may
      explain the phenotypic heterogeneity of the disorder and its variable penetrance.
      METHODS: We used denaturing HPLC (DHPLC) for rapid DNA scanning of the HFE (exons
      2, 3, and 4), hepcidin, and TfR2 (exons 2, 4 and 6) genes in a cohort of 657
      individuals with altered indicators of iron status. RESULTS: DHPLC identification
      of C282Y and H63D HFE alleles was in perfect agreement with the restriction
      endonuclease assay. Fourteen DNA samples were heterozygous for the HFE S65C
      mutation. In addition, we found novel mutations: two in HFE (R66C in exon 2 and
      R224G in exon 4), one in the hepcidin gene (G71D), and one in TfR2 (V22I), plus
      several intronic or silent substitutions. Six of the seven individuals with
      hepcidin or TfR2 coding mutations carried also HFE C282Y or S65C mutations.
      CONCLUSION: DHPLC is an efficient method for mutational screening for the genes
      involved in hereditary hemochromatosis and for the study of their copresence.

PMID- 14633870
TI  - Population-based study of repeat laboratory testing.
AB  - BACKGROUND: Test repetition could be a readily modifiable component of laboratory
      utilization. Laboratory test repetition has not been rigorously studied at a
      population-based level. Our objective was to determine the prevalence of, and
      charges associated with, repetition of eight common laboratory tests. METHODS: We
      performed a cross-sectional study using high-quality, population-based clinical
      databases that included adults in Eastern Ontario, Canada, between September 1999
      and September 2000 for incidence of repeating eight common laboratory tests
      (hemoglobin, sodium, creatinine, thyrotropin, total cholesterol, HDL-cholesterol,
      ferritin, and hemoglobin A(1C)). Tests were classified as potentially redundant
      if repeated within the test's baseline testing interval. For creatinine, sodium,
      and hemoglobin, only tests repeated in the community were considered. For a
      sensitivity analysis, we varied the repeat interval by 25%, excluded tests
      repeated by different physicians, and excluded repeats of normal tests. RESULTS:
      Almost 4 million tests were conducted during the study year. Most tests (76%)
      were conducted on patients in the community. More than one-half of all people in
      the population had at least one laboratory test, with an overall testing rate of
      367 tests per 100 people per year. Repeat testing within 1 month accounted for
      30% of all utilization (109 repeat tests per 100 people per year). Repetition was
      more common in hospitalized patients, varied extensively among tests, and was
      concentrated in a limited number of people. For the eight tests included in the
      study, charges of potentially redundant repetition in adults totaled between 13.9
      and 35.9 million dollars (Canadian) annually. CONCLUSIONS: Laboratory test
      repetition is very common, makes up a significant component of overall test
      utilization, and is costly.

PMID- 14633869
TI  - Assessment of immunoreactive synthetic peptides from the structural proteins of
      severe acute respiratory syndrome coronavirus.
AB  - BACKGROUND: The widespread threat of severe acute respiratory syndrome (SARS) to
      human life has spawned challenges to develop fast and accurate analytical methods
      for its early diagnosis and to create a safe antiviral vaccine for preventive
      use. Consequently, we thoroughly investigated the immunoreactivities with patient
      sera of a series of synthesized peptides from SARS-coronavirus structural
      proteins. METHODS: We synthesized 41 peptides ranging in size from 16 to 25 amino
      acid residues of relatively high hydrophilicity. The immunoreactivities of the
      peptides with SARS patient sera were determined by ELISA. RESULTS: Four epitopic
      sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N
      proteins, respectively, were detected by screening synthesized peptides. Notably,
      N371 and N385, located at the COOH terminus of the N protein, inhibited binding
      of antibodies to SARS-coronavirus lysate and bound to antibodies in >94% of
      samples from SARS study patients. N385 had the highest affinity for forming
      peptide-antibody complexes with SARS serum. CONCLUSIONS: Five peptides from SARS
      structural proteins, especially two from the COOH terminus of the N protein,
      appear to be highly immunogenic and may be useful for serologic assays. The
      identification of these antigenic peptides contributes to the understanding of
      the immunogenicity and persistence of SARS coronavirus.

PMID- 14633871
TI  - Use of lyophilized calibrant plasmas for simplified international normalized
      ratio determination with a human tissue factor thromboplastin reagent derived
      from cultured human cells.
AB  - BACKGROUND: For monitoring of treatment with oral anticoagulants, the clotting
      time obtained in the prothrombin time (PT) test is transformed to the
      International Normalized Ratio (INR) with use of a system-specific International
      Sensitivity Index (ISI). The calibrant plasma procedure (CPP) is an alternative
      approach to INR calculation based on the use of a set of lyophilized plasmas with
      assigned INRs. METHODS: With the CPP, a linear relationship is established
      between log(PT) and log(INR), using orthogonal regression. CPP was validated for
      Simplastin HTF, a new human tissue factor reagent derived from cultured human
      cells. CPP precision was assessed as the CV of the slope of the regression line.
      The accuracy of the CPP was determined by comparing the INR obtained with the CPP
      with that obtained with the established ISI-based reference method. INRs of the
      calibrants were assigned by different routes: by manufacturer (consensus
      labeling) or by use of Simplastin HTF or International Reference Preparations
      (IRPs; rTF/95 or RBT/90). RESULTS: The mean CV of the CPP regression slope ranged
      from 1.0% (Simplastin HTF reagent-specific INR) to 2.4% (INR assigned with
      rTF/95). INRs calculated with the CPP were similar to those obtained with the
      reference method, but when the routes for assigning INRs to the calibrant plasmas
      were compared, the mean difference in INR between CPP and the reference method
      was smaller with Simplastin HTF reagent-specific values. In several (but not all)
      cases, this difference was significant (P <0.05, t-test). CONCLUSION: CPP can be
      used for local INR determination, but better precision and accuracy are obtained
      with reagent-specific INRs compared with INR assignment by consensus labeling or
      IRP.

PMID- 14633872
TI  - Physiologic determinants of endothelin concentrations in human saliva.
AB  - BACKGROUND: Salivary endothelin (ET) concentrations have been shown to correlate
      with disease severity in patients with chronic heart failure (CHF). We undertook
      the present study to evaluate the stability of salivary ET under different
      handling conditions to assess its suitability as a biochemical marker in
      screening, diagnosis, and management of CHF. METHODS: Saliva samples were
      collected from healthy individuals and/or CHF patients, subjected to different
      handling conditions, and then stored at -80 degrees C until assayed by an ELISA
      for ET. RESULTS: Salivary ET concentrations showed a time-dependent increase
      during storage at room temperature. After 72 h of incubation at room temperature,
      ET increased approximately 2.8-fold (P = 0.03). Simultaneously, salivary big ET
      showed a time-dependent 11.2-fold decrease (P <0.0001). This activity was blocked
      by an ET-converting enzyme (ECE) inhibitor, suggesting that these changes were
      attributable to ECE-dependent cleavage of endogenous big ET in saliva. Ex vivo
      conversion was also observed when samples were stored at 4 degrees C, but the
      magnitude of these changes was markedly smaller (P <0.0001). Posture also
      affected salivary ET concentrations in CHF patients. With a change from supine to
      seated rest, salivary ET concentrations increased 1.5- and 1.8-fold after 20 and
      40 min, respectively (P = 0.01). With a return to supine rest, salivary ET
      concentrations returned to baseline concentrations (P = 0.008). CONCLUSIONS:
      These data suggest that saliva sampling and handling conditions could markedly
      affect measurement of salivary ET. In particular, care should be taken to
      minimize ECE-dependent enzymatic conversion of endogenous big ET in saliva.

PMID- 14633873
TI  - Prognostic value of combination of cardiac troponin T and B-type natriuretic
      peptide after initiation of treatment in patients with chronic heart failure.
AB  - BACKGROUND: Recent studies have suggested that cardiac troponin T (cTnT) and
      troponin I may detect ongoing myocardial damage involved in the progression of
      chronic heart failure (CHF). This study was prospectively designed to examine
      whether the combination of cTnT, a marker for ongoing myocardial damage, and B
      type natriuretic peptide (BNP), a marker for left ventricular overload, would
      effectively stratify patients with CHF after initiation of treatment. METHODS: We
      measured serum cTnT, plasma BNP, and left ventricular ejection fraction (LVEF) on
      admission for worsening CHF [New York Heart Association (NYHA) functional class
      III to IV] and 2 months after initiation of treatment to stabilize CHF (n = 100;
      mean age, 68 years). RESULTS: Mean (SD) concentrations of cTnT [0.023 (0.066) vs
      0.063 (0.20) micro g/L] and BNP [249 (276) vs 753 (598) ng/L], percentage
      increased cTnT (>0.01 micro g/L; 35% vs 60%), NYHA functional class [2.5 (0.6) vs
      3.5 (5)], and LVEF [43 (13)% vs 36 (12)%] were significantly (P <0.01) improved 2
      months after treatment compared with admission. During a mean follow-up of 391
      days, there were 44 cardiac events, including 12 cardiac deaths and 32
      readmissions for worsening CHF. On a stepwise Cox regression analysis, increased
      cTnT and BNP were independent predictors of cardiac events (P <0.001). cTnT >0.01
      micro g/L and/or BNP >160 ng/L 2 months after initiation of treatment were
      associated with increased cardiac mortality and morbidity rates. CONCLUSION: The
      combination of cTnT and BNP measurements after initiation of treatment may be
      highly effective for risk stratification in patients with CHF.

PMID- 14633874
TI  - Effects of LDL, cholesterol, and their oxidized forms on the precipitation
      kinetics of calcium phosphates.
AB  - BACKGROUND: LDL, cholesterol, and their oxidized forms are known cardiovascular
      risk factors and are often found in atherosclerotic lesions of various stages.
      Little is known, however, about whether they are directly involved in the
      formation of calcium phosphate compounds. METHODS: We used the pH-stat technique
      to follow the kinetics of calcium phosphate precipitation at pH 7.4, 37 degrees
      C, and ionic strength 0.150 mol/L, in the presence or absence of LDL, oxidized
      LDL, cholesterol, cholestane-3beta,5alpha,6beta-triol, and cholesteryl linoleate.
      The precipitates were characterized by x-ray diffraction, scanning and
      transmission electronic microscopy coupled with energy-dispersion x-ray analysis,
      and inductively coupled plasma atomic emission spectroscopy. RESULTS: Under the
      experimental conditions, LDL (14.8 and 43.1 mg/L protein) had no significant
      effect on the precipitation kinetics. Oxidized LDL (14.8 and 43.1 mg/L protein)
      prolonged the nucleation phase and diminished the amount of total precipitate,
      and both the extent of oxidation and the concentration of the protein affected
      the kinetics. Cholesterol microcrystals (71.4 and 143 mg/L) made the nucleation
      phase shorter (300 min vs 390 min for the control), and the precipitated
      particles had an organic core and a shell composed of calcium phosphates. L-alpha
      Phosphatidylcholine vesicles (143 mg/L), cholesterol (71.4 mg/L)/phospholipid
      (143 mg/L) mixed vesicles, cholesteryl linoleate (143 mg/L), and cholestane
      3beta,5alpha,6beta-triol (71.4 mg/L) prolonged the nucleation phase. CONCLUSIONS:
      LDL is not involved directly in the precipitation of calcium phosphates. Oxidized
      LDL inhibits both nucleation and crystal growth, possibly by attracting calcium
      ions in the solution and thus reducing supersaturation. Cholesterol microcrystals
      serve as seeds for the precipitation of hydroxyapatite, whereas L-alpha
      phosphatidylcholine, cholesteryl linoleate, and cholestane-3beta,5alpha,6beta
      triol exhibit inhibitive effects on the nucleation of calcium phosphates.

PMID- 14633875
TI  - Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to
      hPTH(1-84) is overproduced in primary and secondary hyperparathyroidism.
AB  - BACKGROUND: To separate non-(1-84)parathyroid hormone [non-(1-84)PTH] from PTH(1
      84), we developed new HPLC gradients and observed that the peak coeluting with
      hPTH(1-84) could be separated into two entities recognized by a cyclase
      activating PTH (CA-PTH) assay that reacts with the first four amino acids of the
      PTH structure. METHODS: Sera from six healthy individuals and five patients with
      primary hyperparathyroidism, and eight pools of sera from patients in renal
      failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15
      20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65-84)
      structure requirement were used to measure basal and fractionated PTH values.
      RESULTS: T-PTH was higher than CA-PTH in all healthy controls [mean (SD), 3.13
      (0.37) vs 2.29 (0.33) pmol/L; P <0.01] and in renal failure patients [47 (35.1)
      vs 33.4 (26.1) pmol/L; P <0.01]. By contrast, CA-PTH concentrations were similar
      to or higher than T-PTH in three of five patients with primary
      hyperparathyroidism [25.7 (26.1) vs 23.1 (24.2) pmol/L; not significant]. The CA
      PTH assay reacted with the hPTH(1-84) peak and with a minor peak different from
      the non-(1-84) peak recognized by the T-PTH assay. This minor peak was not
      recognized by the T-PTH assay. It represented 8 (2)% of CA-PTH in controls, 25
      (23)% in patients with primary hyperparathyroidism, and 22 (7)% in renal failure
      patients, assuming equimolar reactivity to hPTH(1-84) in the CA-PTH assay. It was
      not oxidized hPTH(1-84), which migrated differently on HPLC and reacted similarly
      in the CA and T-PTH assays. CONCLUSIONS: This new molecular form of PTH has
      structural integrity of the (1-4) region but presumably is modified in the region
      (15-20), which is usually recognized by the T-PTH assay. Its clinical
      implications remain to be defined.

PMID- 14633876
TI  - Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy.
AB  - BACKGROUND: Early diagnosis of ectopic pregnancy uses ultrasound with serial
      measurements of total human chorionic gonadotropin (hCG). The objective of this
      study was to explore the possibility that an isolated measurement of hCG
      isoforms/subunits rather than total hCG could be used as a single test for
      ectopic pregnancy. METHODS: Total and intact hCG, free hCG beta- and alpha
      subunits (hCGbeta and -alpha), and hCG beta-core fragment were measured by RIA
      and IRMA in the serum and urine of 76 women presenting at outpatient emergency
      departments with a positive pregnancy test, lower abdominal pain, and/or vaginal
      bleeding. Final diagnoses were based on outcomes of pregnancies and tissue
      histology. RESULTS: Twenty-seven of the 76 women were subsequently diagnosed with
      viable pregnancies, 37 with spontaneous miscarriage, and 12 with ectopic
      pregnancy. Concentrations of all forms of hCG were lower in cases of ectopic
      pregnancy and spontaneous miscarriage than in viable pregnancies. Serum samples
      gave better results than urine samples. The free hCGbeta isoform (P <0.0001) had
      100% sensitivity at a specificity of 79% at a 281 pmol/L (6.5 micro g/L) cutoff.
      Total hCG (P = 0.005) had comparable ROC characteristics with a 100% sensitivity
      and 68% specificity at a cutoff value of 1053 pmol/L (375 IU/L). Neither hCGbeta
      (P = 0.7) nor total hCG (P = 0.4) could distinguish ectopic pregnancies from
      spontaneous miscarriage. CONCLUSION: Measurement of serum free hCGbeta at the
      time of presentation can identify women with a high probability of ectopic
      pregnancy who may benefit from closer surveillance, reducing the risk of tubal
      rupture.

PMID- 14633877
TI  - Inductively coupled plasma mass spectrometric analysis of calcium isotopes in
      human serum: a low-sample-volume acid-equilibration method.
AB  - BACKGROUND: Analytical methods for measuring the calcium isotope distribution in
      enriched human serum samples that use low blood volumes, simple preparation
      methods, and rapid analysis are important in clinical studies of calcium
      kinetics. Previously, sample preparation by oxalate precipitation typically
      required 500 micro L of serum. This method was time-consuming, and the blood
      volume required was limiting in circumstances when only a small amount of serum
      could be obtained. METHODS: Serum was collected from humans who were administered
      (42)Ca, and 20 micro L of serum was mixed with 2 mL of 0.22-0.67 mol/L HNO(3) at
      room temperature for between 1 min and 16 h. The (42)Ca/(43)Ca ratio in the
      supernatant was measured by a magnetic sector inductively coupled plasma mass
      spectrometer (ICP-MS). Calcium isotope ratios from these equilibration solutions
      were compared with data from oxalate-precipitated serum samples to determine the
      optimum equilibrium time and the effect of acid concentration on equilibrium.
      RESULTS: Various amounts of aggregated particles developed in different acid
      serum mixtures. These affected the time required for isotope equilibration in the
      mixture. The shortest equilibrium time needed for the calcium isotopes varied
      from 1 to 6 h for samples acidified with 0.22-0.45 mol/L HNO(3). Data obtained
      from these solutions were consistent with data from oxalate-precipitated calcium.
      The precision of (42)Ca/(43)Ca ratio measurements was better than 0.5%.
      CONCLUSIONS: We have developed a simple, rapid sample preparation technique for
      ICP-MS analysis in which 20 micro L of serum can be used for accurate measurement
      of the calcium isotope distribution in a sample with good precision and a rapid
      analysis time.

PMID- 14633878
TI  - Simultaneous determination of tocotrienols, tocopherols, retinol, and major
      carotenoids in human plasma.
AB  - BACKGROUND: Epidemiologic evidence suggests that the concentrations of
      antioxidant vitamins in human plasma may play an important role in numerous
      chronic diseases, such as cancer and cardiovascular disease. However, methods for
      simultaneous measurement of these antioxidants are scarce. We developed and
      validated a new HPLC method for simultaneous determination of these vitamers in
      human plasma that uses a novel column-switching approach. METHODS: The new method
      uses liquid-liquid extraction and isocratic separation with two monomeric C(18)
      columns maintained at 35 and 4 degrees C coupled with ultraviolet-visible and
      fluorometric detection. This method could separate 14 vitamers and 3 internal
      standards within 27 min. No additional modifier was required; the mobile phase
      was acetonitrile-methanol (65:35 by volume), and the flow rate was 1 mL/min.
      RESULTS: For photodiode array detection, the detection limits (signal-to-noise
      ratio >3) were 0.02 mg/L for beta-carotene, lutein, zeaxanthin, and
      canthaxanthin; 0.01 mg/L for all-trans-retinol, beta-cryptoxanthin, alpha
      carotene, and lycopene; and 0.1 mg/L for all tocopherols and tocotrienols. The
      detection limit was at least 25-fold lower (0.004 mg/L) when fluorometry was used
      for measurement of delta-, gamma-, and alpha-tocotrienol and delta-tocopherol
      compared with ultraviolet detection. The recovery and imprecision of the assay
      were generally >90% and <10%, respectively. CONCLUSIONS: This new method
      separates a wide range of fat-soluble antioxidant vitamins in human plasma,
      including six carotenoids, three isoforms of tocotrienols and tocopherols (delta
      , gamma-, and alpha-), and all-trans-retinol. The overall findings suggest that
      our method is faster, more sensitive, and more comprehensive than existing
      methods.

PMID- 14633879
TI  - Cobalamin status and its biochemical markers methylmalonic acid and homocysteine
      in different age groups from 4 days to 19 years.
AB  - BACKGROUND: Recent data indicate that cobalamin and folate status, including the
      metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo
      marked changes during childhood, particularly during the first year. METHODS:
      Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were
      determined in a cross-sectional study of 700 children, ages 4 days to 19 years.
      RESULTS: During the first 6 months, serum cobalamin was lower than and plasma
      MMA, tHcy, and serum folate were higher than the concentrations detected in the
      other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy
      concentrations were >0.78 and >75 micro mol/L, respectively. In older children
      (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median
      plasma MMA remained low (<0.26 micro mol/L), median plasma tHcy was low (<6 micro
      mol/L) and increased from the age of 7 years on, and serum folate gradually
      decreased. Plasma MMA was inversely associated with cobalamin (r = -0.4) in both
      age groups, but across the whole range of cobalamin concentrations, MMA was
      markedly higher in infants (< or =6 months) than in older children. Plasma tHcy
      showed a strong negative correlation to cobalamin (r = -0.52) but not to serum
      folate in infants < or =6 months. In older children, tHcy showed the expected
      association with both cobalamin (r = -0.48) and folate (r = -0.51). CONCLUSIONS:
      In infants 6 weeks to 6 months, concentrations of the metabolic markers MMA and
      tHcy were higher than in the other age groups and strongly correlated to
      cobalamin, whereas in older children, both makers showed correlations to
      cobalamin and folate concentrations documented in adults. Whether this metabolic
      profile in infants is explained by impaired cobalamin status, which in turn may
      have long-term effects on psychomotor development, remains to be addressed in
      intervention studies.

PMID- 14633880
TI  - Holotranscobalamin as an indicator of dietary vitamin B12 deficiency.

PMID- 14633881
TI  - Haplotype structure of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and its
      relationship to serum total bilirubin concentration in a male Korean population.

PMID- 14633882
TI  - Recombinant human intrinsic factor expressed in plants is suitable for use in
      measurement of vitamin B12.

PMID- 14633883
TI  - Effect of anticoagulants and storage temperature on the stability of receptor
      activator for nuclear factor-kappa B ligand and osteoprotegerin in plasma and
      serum.

PMID- 14633884
TI  - Serial analysis of the plasma concentration of SARS coronavirus RNA in pediatric
      patients with severe acute respiratory syndrome.

PMID- 14633885
TI  - Applicability of an assay for routine monitoring of highly variable
      concentrations of olanzapine based on HPLC with mass spectrometric detection.

PMID- 14633887
TI  - Reliability of IFCC method for lactate dehydrogenase measurement in lithium
      heparin plasma samples.

PMID- 14633886
TI  - Anti-tissue transglutaminase antibodies in arthritic patients: a disease-specific
      finding?

PMID- 14633888
TI  - Comparison of gene expression profiles in laser-microdissected, nonembedded, and
      OCT-embedded tumor samples by oligonucleotide microarray analysis.

PMID- 14633889
TI  - Frequencies of interleukin 1 gene polymorphisms in Koreans.

PMID- 14633890
TI  - Detection of hereditary persistence of alpha-fetoprotein by conformation
      sensitive gel electrophoresis analysis.

PMID- 14633891
TI  - Plasma procalcitonin and C-reactive protein concentrations in pediatric patients
      with Epstein-Barr virus infection.

PMID- 14633892
TI  - "MacroLH": anomalous molecular form that behaves as a complex of luteinizing
      hormone (LH) and IgG in a patient with unexpectedly high LH values.

PMID- 14633893
TI  - Measurement of whole-blood potassium--is it clinically safe?

PMID- 14633894
TI  - New scenarios in antidoping research.

PMID- 14633895
TI  - Hemoglobin in samples with leukocytosis can be measured on ABL 700 series blood
      gas analyzers.

PMID- 14633896
TI  - Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with
      severe acute respiratory syndrome.

PMID- 14633897
TI  - Improved real-time PCR assay for homogeneous multiplex genotyping of four CYP2C9
      alleles with hybridization probes.

PMID- 14633898
TI  - Protein microarrays: a literature survey.

PMID- 14633899
TI  - Aminoglycoside interference in the pyrogallol red-molybdate protein assay is
      increased by the addition of sodium dodecyl sulfate to the dye reagent.

PMID- 14633900
TI  - Quantification and integrity analysis of DNA in the stool of colorectal cancer
      patients may represent a complex alternative to fecal occult blood testing.

PMID- 14633907
TI  - Genetic effects on baseline values of C-reactive protein and serum amyloid a
      protein: a comparison of monozygotic and dizygotic twins.
AB  - BACKGROUND: C-Reactive protein (CRP) and serum amyloid A protein (SAA) are
      exquisitely sensitive acute-phase reactants, but their baseline values are
      surprisingly constant in individuals in the general population. These values,
      especially of CRP, are associated with future atherothrombotic events, and the
      determinants of baseline CRP and SAA concentration are therefore of considerable
      interest. METHODS: CRP and SAA concentrations were measured by well-validated
      automated microparticle capture enzyme immunoassays, standardized on the
      respective WHO International Reference Standards, in serum from 146 monozygotic
      and 164 dizygotic healthy female UK twin pairs from the general population, with
      mean (range) ages of 58.0 (40-69.6) and 55.7 (40-70.3) years, respectively, who
      were also very closely matched for height, weight, body mass index, blood
      pressure, and lifestyle variables. Statistical modeling based on variance
      components analysis was used to estimate the genetic contribution to the observed
      values. RESULTS: As reported previously, CRP values were associated with body
      mass index, smoking, and hormone replacement therapy. After exclusion of the few
      samples with CRP concentrations >10 mg/L, which indicate an ongoing acute-phase
      response rather than baseline values, and inclusion of adjustments for all known
      confounding variables, there was significantly higher correlation of CRP and SAA
      results among monozygotic than among dizygotic twins. The estimated
      hereditability (95% confidence interval) of baseline values was 52% (40-62%) for
      CRP and 59% (49-67%) for SAA. CONCLUSION: There is a substantial genetic
      contribution to baseline serum concentrations of CRP and SAA.

PMID- 14633908
TI  - Detection of hemoglobin-based oxygen carriers in human serum for doping analysis:
      screening by electrophoresis.
AB  - BACKGROUND: Hemoglobin-based oxygen carriers (HBOCs) have recently been included
      in the International Olympic Committee and World Anti-Doping Agency lists of
      substances and methods prohibited in sports. To enforce this rule and deter abuse
      of HBOCs in elite sports, it is necessary to develop HBOC-specific screening and
      confirmation tests that are the usual steps in antidoping control analysis.
      METHODS: We developed a screening method based on electrophoresis of serum
      samples cleared of haptoglobin (Hp). Four successive steps (immunoprecipitation
      of Hp, electrophoresis of the cleared serum, Western blotting of the separated
      proteins, and detection of hemoglobin-related molecules based on the peroxidase
      properties of the heme moiety), provided electropherograms that could be easily
      interpreted in terms of the presence of HBOCs. This method was tested with serum
      samples enriched with various types of HBOCs: polymerized, conjugated, and cross
      linked hemoglobins. It was also applied to blood samples collected from 12
      healthy volunteers who had been infused with either 30 or 45 g of Hemopure, a
      glutaraldehyde-polymerized bovine hemoglobin. RESULTS: The method clearly
      detected the presence in serum of the various types of HBOCs tested and
      demonstrated no possible confusion with endogenous hemoglobin that may be present
      in cases of hemolysis. The test was able to detect Hemopure for 4-5 days after
      administration of 45 g to healthy individuals. CONCLUSIONS: The electrophoretic
      method is a simple, fast, and sensitive procedure that appears to fulfill the
      criteria of a screening test for the presence of HBOCs in antidoping control
      samples.

PMID- 14633909
TI  - Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by
      biochemical assays.
AB  - BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is
      caused by mutations in the gene encoding thymidine phosphorylase (TP). The
      clinical manifestations of MNGIE are recognizable and homogeneous, but in the
      early stages, the disease is often misdiagnosed. This study assesses the
      reliability of biochemical assays to diagnose MNGIE. METHODS: We studied 180
      patients with clinical features suggestive of MNGIE, 14 asymptomatic TP mutation
      carriers, and 20 controls. TP enzyme activity in the buffy coat was determined by
      a fixed-time method, and the plasma nucleosides thymidine (dThd) and deoxyuridine
      (dUrd) were assessed by a gradient-elution reversed phase HPLC method. TP was
      sequenced through standard procedures in patients who met the clinical criteria
      for MNGIE. RESULTS: Twenty-five of the 180 patients fulfilled the clinical
      criteria for MNGIE and had homozygous or compound heterozygous TP mutations. All
      had drastically decreased TP activity [mean (SD), 10 (15) nmol thymine formed. h(
      1). (mg protein)(-1) vs 634 (217) nmol thymine formed. h(-1). (mg protein)(-1)
      for the controls]. Relative to the control mean, TP activities were reduced to
      35% in mutation carriers and 65% in MNGIE-like patients. All 25 MNGIE patients
      had detectable plasma dThd [8.6 (3.4) micromol/L] and dUrd [14.2 (4.4)
      micromol/L]. Controls, carriers, and MNGIE-like patients showed no detectable
      plasma dThd and dUrd. CONCLUSIONS: We propose a diagnostic algorithm based on the
      determination of plasma dThd and dUrd, TP activity in buffy coat, or both to make
      a definitive diagnosis of MNGIE. Increased concentrations of dThd (>3 micromol/L)
      and dUrd (>5 micromol/L) in plasma or a decrease in buffy coat TP activity to
      </=8% relative to controls is sufficient to diagnose MNGIE.

PMID- 14633910
TI  - Immunopeptidometric assay for enzymatically active prostate-specific antigen.
AB  - BACKGROUND: Determinations of certain forms of prostate-specific antigen (PSA)
      have been shown to increase the specificity for prostate cancer (PCa). One such
      variant, proteolytically active PSA, is a potentially useful tumor marker, but it
      is not specifically recognized by antibodies. Using phage display libraries, we
      previously identified a "family" of peptides that bind specifically to active
      PSA. We used these to develop an immunopeptidometric assay (IPMA) that
      specifically detects this form of PSA. METHODS: Microtitration plates coated with
      a PSA antibody were used to capture PSA, and a PSA-binding glutathione S
      transferase (GST) fusion peptide was used as a tracer. Bound tracer was detected
      with an antibody to GST labeled with a europium chelate. PSA isoenzymes with high
      and low enzymatic activity were used to study binding specificity. RESULTS: The
      IPMA detected enzymatically active PSA but not internally cleaved PSA and pro
      PSA, which are enzymatically inactive. The assay detected 1-10% of free PSA in
      serum from PCa patients. CONCLUSIONS: Peptides identified by phage display can be
      used to develop assays with unique specificities for enzymatically active PSA.
      IPMA represents a new assay principle with wide potential utility.

PMID- 14633912
TI  - Diagnostic accuracy and prognostic relevance of the measurement of cardiac
      natriuretic peptides: a review.
AB  - BACKGROUND: The pathophysiologic and clinical relevance of cardiac natriuretic
      hormone (CNH) assays has been investigated in numerous experimental and clinical
      studies. Authors have sought to evaluate the diagnostic accuracy and prognostic
      relevance of the measurement of CNHs according to evidence-based laboratory
      medicine principles. METHODS: In June 2003, we ran a computerized literature
      search on National Library of Medicine using keywords "ANP" and "BNP" and found
      more than 12 300 and 1200 articles, respectively. A more refined search with
      keywords "ANP or BNP assay" extracted approximately 7000 and 800 articles,
      respectively. Only studies specifically designed to evaluate the diagnostic
      accuracy and prognostic relevance of CNH measurements were selected from this
      huge mass of articles to be discussed in this review. CONTENT: Several studies
      suggested that CNH assays may be clinically useful for the screening and
      classification of patients with heart failure, as a prognostic marker in
      cardiovascular disease, in the follow-up of patients with heart failure, and
      because they may reduce the need for further cardiac investigation. However, it
      is difficult to compare even the best-designed studies because not only did the
      authors evaluate different populations, they also used different gold standards.
      CONCLUSIONS: CNH assays and conventional diagnostic work-ups provide
      complementary information for evaluation of the presence and severity of cardiac
      dysfunction and clinical disease. Several aspects of CNH assays are still to be
      elucidated, and further work is needed to carefully assess their diagnostic
      accuracy and prognostic value in cardiac disease.

PMID- 14633913
TI  - Real-time quantitative reverse transcription-PCR for cyclin D1 mRNA in blood,
      marrow, and tissue specimens for diagnosis of mantle cell lymphoma.
AB  - BACKGROUND: Overexpression of cyclin D1 mRNA, found in mantle cell lymphoma
      (MCL), is a critical diagnostic marker. We investigated the use of real-time
      reverse transcription-PCR (RT-PCR) for cyclin D1. METHODS: We studied 97 fresh
      specimens (50 blood, 30 bone marrow, 15 lymph node, and 2 other samples) from
      patients diagnosed with a variety of lymphoproliferative diseases, including 25
      cases of MCL. We used real-time quantitative RT-PCR to evaluate cyclin D1 mRNA
      expression. Because blood and marrow specimens may contain only a minority of
      potentially malignant cells (as opposed to most lymph nodes) and to increase
      sensitivity, we normalized the cyclin D1 mRNA concentrations to mRNA of a B-cell
      specific marker, CD19, as well as to previously characterized beta(2)
      microglobulin mRNA. RESULTS: In 16 of 21 cases of MCL with overt disease, the
      ratio of cyclin D1 mRNA to beta(2)-microglobulin mRNA was increased, but all 21
      cases showed increased ratios of cyclin D1 mRNA to CD19 mRNA. Cyclin D1 mRNA was
      low or undetectable in various lymphoproliferative diseases, including cases of
      ambiguous immunophenotype. The mRNA ratios were stable over 3-7 days of sample
      storage. CONCLUSION: Quantitative RT-PCR for cyclin D1 mRNA normalized to CD19
      mRNA can be used in the diagnosis of MCL in blood, marrow, and tissue.

PMID- 14633915
TI  - Validation of a rapid and sensitive liquid chromatography-tandem mass
      spectrometry method for free and total mycophenolic acid.
AB  - BACKGROUND: Because mycophenolic acid (MPA) is highly protein bound and because
      the free fraction is the pharmacologically active portion, a rapid, reliable, and
      sensitive procedure is required to study the relationship between free MPA and
      treatment efficacy/toxicity. Liquid chromatography-tandem mass spectrometry is
      ideally suited for such a method. METHODS: Free MPA was isolated from plasma by
      ultrafiltration. An online extraction cartridge with a column-switching
      technique, analytical liquid chromatography over an Aqua Perfect C(18) column,
      and electrospray tandem mass spectrometry was used to quantify free and total
      MPA. To investigate ion suppression, a continuous infusion of MPA was introduced
      into the effluent from the HPLC column, and different ultrafiltrates and
      extracted plasma samples were injected on the column. RESULTS: A chromatographic
      run time of 4 min separated MPA from metabolites and internal standard, thereby
      avoiding interference from in-source fragmentation. Ion suppression occurred well
      before elution of MPA and internal standard. The lower limit of quantification
      for free MPA was 0.5 microg/L, and the method was linear to 1000 microg/L.
      Interassay imprecision (CV) was <10% for free MPA (0.5-333 microg/L). Agreement
      was good for free MPA (n = 52) and total MPA (n = 106) between the proposed
      method and a validated HPLC method with ultraviolet detection. The Passing-Bablok
      regression line was: y = 0.95x + 0.27 microg/L for free MPA and y = 0.98x + 0.03
      mg/L for total MPA. CONCLUSIONS: The presented method allows the accurate,
      precise, and rapid determination of free and total MPA in plasma over a wide
      analytical range covering the concentrations relevant to pharmacokinetic studies
      and routine monitoring of this drug.

PMID- 14633920
TI  - [13C]Nandrolone excretion in trained athletes: interindividual variability in
      metabolism.
AB  - BACKGROUND: Nandrolone is one of the most abused anabolic steroids, and its use
      in doping is increasing, as revealed by numerous positive cases during recent
      years in various sports. Different authors have reported the possible natural
      production of nandrolone metabolites in humans, and some of these authors argued
      that exhaustive exercise could increase nandrolone production in the body or
      induce dehydration and consequently lead to an increase of nandrolone metabolites
      in urine. METHODS: Volunteers (n = 22) ingested two 25-mg doses of
      [(13)C]nandrolone at 24-h intervals and collected urine specimens for 5 days. The
      labeled nandrolone metabolites 19-norandrosterone and 19-noretiocholanolone were
      identified and quantified by gas chromatography-mass spectrometry. RESULTS:
      Interindividual variability was observed in nandrolone excretion patterns and
      kinetics, as well as for the noretiocholanolone:norandrosterone ratio. The
      amounts of nandrolone metabolites measured at the excretion peak varied between
      1180 and 38 661 microg/L for norandrosterone and 576 and 12 328 microg/L for
      noretiocholanolone. At the end of the excretion period, the
      noretiocholanolone:norandrosterone ratio was sometimes >1. The analysis of
      numerous spot-urine samples allowed the determination of an acceptable
      correlation between urinary creatinine and specific gravity for placebo- and
      steroid-treated individuals: y = 0.0052ln(x) + 1.0178 (r(2) = 0.8142) and y =
      0.0068ln(x) + 1.0172 (r(2) = 0.7730), respectively. CONCLUSIONS: The excretion
      kinetics and patterns of labeled nandrolone show interindividual variability.
      More investigations are currently underway to estimate the influence of
      exhaustive exercises on excretion of labeled nandrolone metabolites in urine.

PMID- 14633923
TI  - Highly recurrent RET mutations and novel mutations in genes of the receptor
      tyrosine kinase and endothelin receptor B pathways in Chinese patients with
      sporadic Hirschsprung disease.
AB  - BACKGROUND: Hirschsprung disease (HSCR) is a congenital disorder characterized by
      an absence of ganglion cells in the nerve plexuses of the lower digestive tract.
      HSCR has a complex pattern of inheritance and is sometimes associated with
      mutations in genes of the receptor tyrosine kinase (RET) and endothelin receptor
      B (EDNRB) signaling pathways, which are crucial for development of the enteric
      nervous system. METHODS: Using PCR amplification and direct sequencing, we
      screened for mutations and polymorphisms in the coding regions and intron/exon
      boundaries of the RET, GDNF, EDNRB, and EDN3 genes of 84 HSCR patients and 96
      ethnically matched controls. RESULTS: We identified 10 novel and 2 previously
      described mutations in RET, and 4 and 2 novel mutations in EDNRB and in EDN3,
      respectively. Potential disease-causing mutations were detected in 24% of the
      patients. The overall mutation rate was 41% in females and 19% in males (P =
      0.06). RET mutations occurred in 19% of the patients. R114H in RET was the most
      prevalent mutation, representing 7% of the patients or 37% of the patients with
      RET mutations. To date, such a high frequency of a single mutation has never been
      reported in unrelated HSCR patients. Mutations in EDNRB, EDN3, and GDNF were
      found in four, two, and none of the patients, respectively. Two patients with
      mutations in genes of the EDNRB pathway also harbored a mutation in RET. Three
      novel and three reported polymorphisms were found in EDNRB, EDN3, and GDNF.
      CONCLUSION: This study identifies additional HSCR disease-causing mutations, some
      peculiar to the Chinese population, and represents the first comprehensive
      genetic analysis of sporadic HSCR disease in Chinese.

PMID- 14633925
TI  - Diagnosis of congenital disorders of glycosylation by capillary zone
      electrophoresis of serum transferrin.
AB  - BACKGROUND: Congenital disorders of glycosylation (CDG) are usually diagnosed by
      isoelectric focusing (IEF) of serum transferrin (Tf). The aim of this study was
      to evaluate capillary zone electrophoresis (CZE) as a diagnostic alternative to
      IEF. METHODS: We performed 792 CZE analyses of Tf, using the CEofix(TM)-CDT
      (carbohydrate-deficient transferrin) assay. Peak identification was based on
      relative migration times (RMTs) to reduce migration variability. RESULTS: Tf
      profiles comprised three main groups (A-C). Groups A and B were characterized by
      one or two dominant tetrasialo-Tf peaks, whereas group C showed a widely variable
      Tf isoform composition. Group A was composed of four subgroups: a major group
      with a typical Tf profile (considered as reference group), two minor groups with
      decreased or moderately increased trisialo-Tf isoform, and a group showing the
      presence of unknown compounds with RMTs similar to mono- and disialo-Tf. However,
      these compounds were absent on IEF. Group C contained all profiles from patients
      with confirmed as well as putative CDG. From the reference group, 99% confidence
      intervals were calculated for the RMTs of the Tf isoforms, and percentiles
      representing the Tf isoform distributions were defined. CONCLUSIONS: All patients
      with abnormal IEF results and confirmed CDG were identified by CZE; thus, this
      method can be used as a diagnostic alternative to IEF in a manner suitable for
      automation. Because whole serum is analyzed, it should be kept in mind that CZE
      profiles can show substances other than Tf.

PMID- 14633929
TI  - N-acetylated metabolites in urine: proton nuclear magnetic resonance
      spectroscopic study on patients with inborn errors of metabolism.
AB  - BACKGROUND: There is no comprehensive analytical technique to analyze N
      acetylated metabolites in urine. Many of these compounds are involved in inborn
      errors of metabolism. In the present study, we examined the potential of proton
      nuclear magnetic resonance ((1)H-NMR) spectroscopy as a tool to identify and
      quantify N-acetylated metabolites in urine of patients with various inborn errors
      of metabolism. METHODS: We performed (1)H-NMR spectroscopy on a 500 MHz
      spectrometer. Using a combination of one- and two-dimensional correlation
      spectroscopy (COSY) (1)H-NMR spectra, we were able to assign and quantify
      resonances of characteristic N-acetylated compounds products in urine of patients
      with 13 inborn errors of metabolism. RESULTS: The disease-specific N-acetylated
      metabolites were excreted at concentrations >100 micromol/mmol of creatinine in
      the patients' urine. In control urine samples, the concentration of individual N
      acetyl-containing compounds was <40 micromol/mmol of creatinine. The combination
      of one- and two-dimensional COSY NMR spectroscopy led to the correct diagnosis of
      nine different inborn errors of metabolism. No abnormalities were observed in the
      spectra of urine from patients with G(M1)- or G(M2)-gangliosidosis. We also
      determined the (1)H-NMR characteristics of N-acetylated metabolites that may be
      relevant to human metabolism. CONCLUSION: (1)H-NMR spectroscopy may be used to
      identify and quantify N-acetylated metabolites of diagnostic importance for the
      field of inborn errors of metabolism.

PMID- 14633931
TI  - Performance of bilirubin determinations in US laboratories--revisited.
AB  - BACKGROUND: The diagnosis and management of hyperbilirubinemia in the newborn
      requires accurate and precise bilirubin determinations. We evaluated the current
      status of bilirubin measurements in US laboratories by examining data submitted
      by laboratories participating in the College of American Pathologists (CAP)
      Neonatal Bilirubin (NB) and Chemistry (C) Surveys. METHODS: We analyzed specimens
      from the CAP NB and C Surveys by the reference method for total bilirubin in
      three laboratories. The reference method bilirubin values were compared with
      bilirubin values reported by Survey participants. RESULTS: The imprecision (CV)
      for all instruments combined (CAP-All Instruments) ranged from 4.7% to 5.6% at
      the bilirubin concentrations tested. The CVs of the four most commonly used
      instruments were smaller, ranging from 1.9% to 4.5%. Differences between
      bilirubin values by the reference method and mean values from the four most
      common instruments ranged from -21.6% to 10.9%. When the same specimens from the
      NB Surveys were used in the C Surveys, the Vitros values were strikingly
      different from those of the NB Surveys. The use of different methods in the NB
      and C Surveys coupled with the presence of a nonhuman protein base and
      ditaurobilirubin (DTB) in the Survey specimens accounted for the discrepant
      results. CONCLUSIONS: The evaluation of accuracy is impossible from the CAP
      Surveys because the specimens consist of bovine serum containing a mixture of
      unconjugated bilirubin and DTB. For the evaluation of accuracy, we recommend that
      Survey specimens consist of human serum enriched with unconjugated bilirubin.

PMID- 14633932
TI  - Overcoming structural constraints to patient utilization of electronic medical
      records: a critical review and proposal for an evaluation framework.
AB  - There are constraints embedded in medical record structure that limit use by
      patients in self-directed disease management. Through systematic review of the
      literature from a critical perspective, four characteristics that either enhance
      or mitigate the influence of medical record structure on patient utilization of
      an electronic patient record (EPR) system have been identified: environmental
      pressures, physician centeredness, collaborative organizational culture, and
      patient centeredness. An evaluation framework is proposed for use when
      considering adaptation of existing EPR systems for online patient access.
      Exemplars of patient-accessible EPR systems from the literature are evaluated
      utilizing the framework. From this study, it appears that traditional information
      system research and development methods may not wholly capture many pertinent
      social issues that arise when expanding access of EPR systems to patients.
      Critically rooted methods such as action research can directly inform development
      strategies so that these systems may positively influence health outcomes.

PMID- 14633934
TI  - Computerized physician order entry: helpful or harmful?
AB  - Computerized physician order entry (CPOE) is touted as a major improvement in
      patient safety, primarily as a result of the Institute of Medicine's 1999 report
      on medical errors and the subsequent formation of the "Leapfrog Group" of
      companies to preferentially direct their employees' health care to those
      institutions that install such systems (as part of directives that "Leapfrog"
      feels will improve patient care). Although the literature suggests that such
      systems have the potential to improve patient outcomes through decrease of
      adverse drug events, actual improvements in medical outcomes have not been
      documented. Installation of such systems could actually increase the number of
      adverse drug events and result in higher overall medical costs, particularly in
      the first few years of their adoption.

PMID- 14633933
TI  - Implementing syndromic surveillance: a practical guide informed by the early
      experience.
AB  - Syndromic surveillance refers to methods relying on detection of individual and
      population health indicators that are discernible before confirmed diagnoses are
      made. In particular, prior to the laboratory confirmation of an infectious
      disease, ill persons may exhibit behavioral patterns, symptoms, signs, or
      laboratory findings that can be tracked through a variety of data sources.
      Syndromic surveillance systems are being developed locally, regionally, and
      nationally. The efforts have been largely directed at facilitating the early
      detection of a covert bioterrorist attack, but the technology may also be useful
      for general public health, clinical medicine, quality improvement, patient
      safety, and research. This report, authored by developers and methodologists
      involved in the design and deployment of the first wave of syndromic surveillance
      systems, is intended to serve as a guide for informaticians, public health
      managers, and practitioners who are currently planning deployment of such systems
      in their regions.

PMID- 14633935
TI  - Computerized physician order entry in U.S. hospitals: results of a 2002 survey.
AB  - OBJECTIVE: To determine the availability of inpatient computerized physician
      order entry in U.S. hospitals and the degree to which physicians are using it.
      DESIGN: Combined mail and telephone survey of 964 randomly selected hospitals,
      contrasting 2002 data and results of a survey conducted in 1997. MEASUREMENTS: 
      AVAILABILITY: computerized order entry has been installed and is available for
      use by physicians; inducement: the degree to which use of computers to enter
      orders is required of physicians; participation: the proportion of physicians at
      an institution who enter orders by computer; and saturation: the proportion of
      total orders at an institution entered by a physician using a computer. RESULTS:
      The response rate was 65%. Computerized order entry was not available to
      physicians at 524 (83.7%) of 626 hospitals responding, whereas 60 (9.6%) reported
      complete availability and 41 (6.5%) reported partial availability. Of 91
      hospitals providing data about inducement/requirement to use the system, it was
      optional at 31 (34.1%), encouraged at 18 (19.8%), and required at 42 (46.2%). At
      36 hospitals (45.6%), more than 90% of physicians on staff use the system,
      whereas six (7.6%) reported 51-90% participation and 37 (46.8%) reported
      participation by fewer than half of physicians. Saturation was bimodal, with 25
      (35%) hospitals reporting that more than 90% of all orders are entered by
      physicians using a computer and 20 (28.2%) reporting that less than 10% of all
      orders are entered this way. CONCLUSION: Despite increasing consensus about the
      desirability of computerized physician order entry (CPOE) use, these data
      indicate that only 9.6% of U.S. hospitals presently have CPOE completely
      available. In those hospitals that have CPOE, its use is frequently required. In
      approximately half of those hospitals, more than 90% of physicians use CPOE; in
      one-third of them, more than 90% of orders are entered via CPOE.

PMID- 14633936
TI  - Some unintended consequences of information technology in health care: the nature
      of patient care information system-related errors.
AB  - Medical error reduction is an international issue, as is the implementation of
      patient care information systems (PCISs) as a potential means to achieving it. As
      researchers conducting separate studies in the United States, The Netherlands,
      and Australia, using similar qualitative methods to investigate implementing
      PCISs, the authors have encountered many instances in which PCIS applications
      seem to foster errors rather than reduce their likelihood. The authors describe
      the kinds of silent errors they have witnessed and, from their different social
      science perspectives (information science, sociology, and cognitive science),
      they interpret the nature of these errors. The errors fall into two main
      categories: those in the process of entering and retrieving information, and
      those in the communication and coordination process that the PCIS is supposed to
      support. The authors believe that with a heightened awareness of these issues,
      informaticians can educate, design systems, implement, and conduct research in
      such a way that they might be able to avoid the unintended consequences of these
      subtle silent errors.

PMID- 14633937
TI  - From comic relief to real understanding; how intestinal gas causes symptoms.
AB  - Gas content and transit appear to conspire with the motor and sensory responses
      of the gut to produce gas related symptoms, both in normal individuals and
      especially in patients with irritable bowel syndrome (IBS). In relation to gas in
      IBS, two questions need to be addressed: do IBS patients produce more gas and
      what are the relationships between intestinal gas and symptoms? The balance of
      evidence seems to indicate that distension is a real phenomenon in IBS and that
      such distension accurately reflects gas content. More problematic is
      extrapolation of the observations relating symptoms to gas transit and retention.

PMID- 14633938
TI  - The virtuosity of virtuality or how real is virtual colonography.

PMID- 14633939
TI  - Diagnosing Lynch syndrome: is the answer in the mouth?

PMID- 14633940
TI  - Bilirubin, a curse and a boon.

PMID- 14633941
TI  - Cognitive modulation of the cerebral processing of human oesophageal sensation
      using functional magnetic resonance imaging.
AB  - BACKGROUND: While cortical processing of visceral sensation has been described,
      the role that cognitive factors play in modulating this processing remains
      unclear. AIM: To investigate how selective and divided attention modulate the
      cerebral processing of oesophageal sensation. METHODS: In seven healthy
      volunteers (six males, mean age 33 years; ranging from 24 to 41 years old) from
      the general community, phasic visual and oesophageal (non-painful balloon
      distension) stimuli were presented simultaneously. During the selective attention
      task, subjects were instructed to press a button either to a change in frequency
      of oesophageal or visual stimuli. During a divided attention task, subjects
      received simultaneous visual and oesophageal stimuli and were instructed to press
      a button in response to a change in frequency of both stimuli. RESULTS:
      Selectively focussing attention on oesophageal stimuli activated the visceral
      sensory and cognitive neural networks (primary and secondary sensory cortices and
      anterior cingulate cortex respectively) while selective attention to visual
      stimuli primarily activated the visual cortex. When attention was divided between
      the two sensory modalities, more brain regions in the sensory and cognitive
      domains were utilised to process oesophageal stimuli in comparison to those
      employed to process visual stimuli (p=0.003). CONCLUSION: Selective and divided
      attention to visceral stimuli recruits more neural resources in both the sensory
      and cognitive domains than attention to visual stimuli. We provide
      neurobiological evidence that demonstrates the biological importance placed on
      visceral sensations and demonstrate the influence of cognitive factors such as
      attention on the cerebral processing of visceral sensation.

PMID- 14633942
TI  - Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric
      cardia and distal oesophagus.
AB  - BACKGROUND: Adenocarcinomas of the gastric cardia and distal oesophagus are at
      present often considered as one clinical entity because of their comparable
      increasing incidence, prognosis, and optimal treatment options. However, it is
      still a matter of debate whether these malignancies have the same pathogenesis
      and genotype. AIMS: The aim of this study was to analyse expression of
      cyclooxygenase 2 (COX-2) in cardia carcinomas, and correlate this expression with
      clinicopathological parameters and survival. The results were compared with the
      prognostic value of COX-2 found for Barrett carcinomas. METHODS: Tumour sections
      of 134 consecutive patients undergoing potentially curative surgery for an
      adenocarcinoma of the gastric cardia and substantially invading the distal
      oesophagus were immunohistochemically stained using a COX-2 monoclonal antibody.
      Specimens were blindly scored based on intensity and extent of COX-2
      immunopositivity. RESULTS: COX-2 expression was negative to weak in 59% ("COX-2
      low") and moderate to strong in 41% ("COX-2 high") of tumours. This was
      significantly lower than in Barrett carcinomas (p<0.0001). COX-2 expression was
      not correlated with any clinicopathological parameter. A correlation between
      elevated COX-2 expression and reduced survival, as described for Barrett
      carcinomas, was not identified for cardiac carcinomas. CONCLUSIONS: There is a
      difference in COX-2 expression with respect to intensity and prognostic
      significance between adenocarcinomas of the gastric cardia and distal oesophagus.
      This suggests a different pathogenesis and different genetic constitution of
      these two cancers. Based on these findings, the role of selective COX-2
      inhibitors in the treatment of adenocarcinomas of the gastric cardia is less
      promising than in Barrett carcinomas.

PMID- 14633943
TI  - Association of interleukin 1B gene polymorphism and gastric cancers in high and
      low prevalence regions in China.
AB  - AIM: Our aim was to study the relationship between interleukin 1B (IL-1B)
      polymorphism, Helicobacter pylori infection, and gastric cancer in high prevalent
      (Shanxi) and low prevalent (Guangdong) regions in China. METHOD: Genomic DNA was
      extracted from peripheral blood of 192 healthy volunteers, 84 gastric cancer
      patients from Guangdong and 169 healthy volunteers, and 86 gastric cancer
      patients from Shanxi. Polymorphisms in IL-1B that encodes IL-1beta and IL-1RN
      that encodes IL-1 receptor antagonist were analysed by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). These polymorphic sites
      include promoter regions of IL-1B at positions +3954, -511 (C-T transition), and 
      31 (T-C transition), and IL-1RN variable tandem repeats. RESULTS: In the low
      prevalence region, the frequencies of the IL-1B +3954 T/T and IL-1RN *2/*2
      genotypes were similar. IL-1B -511T/T genotype frequency was significantly higher
      among patients with gastric cancer (25.0%) than control subjects (12.5%)
      (chi2=6.7, p=0.01). In the high prevalence region, the frequencies of the IL-1B
      +3954T/T and -511T/T genotypes and the IL-1RN *2/*2 genotype in the cancer and
      control groups were similar. IL-1B -31C/C genotype frequency was significantly
      higher among patients with gastric cancer (90.0%) than controls (78.0%)
      (chi2=5.0, p=0.025). Compared with the low prevalence region, control subjects
      from the high prevalence region had a higher frequency of the IL-1B -511T/T
      genotype (23.0% v 12.5%; chi2=7.0, p<0.008). While H pylori infection alone had
      only a modest effect on the risk of gastric cancer development (odds ratio (OR)
      5.0 (95% confidence interval (CI) 1.5-16.3)), combined with the IL-1B -511T/T
      genotype the risk was markedly elevated (OR 17.1, 95% CI 3.8-76.4). CONCLUSION:
      IL-1B -511T/T genotypes are associated with gastric cancer in China. The effect
      of IL-1B polymorphism is less obvious in areas of high prevalence for gastric
      cancer.

PMID- 14633944
TI  - Intestinal epithelial exosomes carry MHC class II/peptides able to inform the
      immune system in mice.
AB  - BACKGROUND: Intestinal epithelial cells secrete exosome-like vesicles. The aim of
      this study was to characterise murine intestinal epithelial exosomes and to
      analyse their capacity to inform the immune system in vivo in mice. METHODS:
      Epithelial exosomes were obtained from the murine epithelial cell line MODE K
      incubated in the presence or absence of interferon gamma (IFN-gamma) together
      with pepsin/trypsin ovalbumin hydrolysate (hOVA) to mimic luminal digestion.
      Exosomes isolated from MODE K conditioned media (EXO-hOVA and EXO-hOVA-IFN) were
      characterised by western blot, peptide mapping, and mass spectrometry. They were
      injected intraperitoneally to C3H/HeN mice to test their immunocompetence.
      RESULTS: MODE K epithelial exosomes displayed major histocompatibility complex
      (MHC) class I and class II (upregulated by IFN-gamma) molecules and tetraspan
      proteins (CD9, CD81, CD82) potentially involved in the binding to target cells.
      A33 antigen, an Ig-like molecule highly specific for intestinal epithelial cells,
      was enriched in exosomes and was also found in mice mesenteric lymph nodes,
      suggesting exosome migration towards the gut associated lymphoid tissues.
      Intraperitoneal injection of EXO-hOVA or EXO-hOVA-IFN did not induce humoral or
      cellular tolerance to OVA in mice. In contrast, exosomes obtained after
      incubation with IFN-gamma (EXO-hOVA-IFN), bearing abundant MHC class II/OVA
      complexes, induced a specific humoral immune response. CONCLUSIONS: Epithelial
      exosomes are antigen presenting vesicles bearing MHC class II/peptide complexes
      that prime for an immunogenic rather than tolerogenic response in the context of
      a systemic challenge. In the intestine, both the mucosal microenvironment and
      local effector cells are probably key players in determining the outcome of the
      immune response to exosome derived epitopes.

PMID- 14633945
TI  - Coeliac disease: in vivo toxicity of the putative immunodominant epitope.
AB  - BACKGROUND: Peptides from alpha-gliadins have been used to characterise the
      immunodominant coeliac toxic epitope. A peptide corresponding to amino acid
      residues 57-73 of A-gliadin causes peripheral blood mononuclear cells from
      coeliac patients to secrete interferon gamma (IFN-gamma); gluten specific small
      intestinal T cell clones proliferate in response to peptides corresponding to
      residues 57-68 and 62-75 of alpha-gliadins. We wished to investigate whether a
      peptide corresponding to residues 56-75 of alpha-gliadins exacerbates coeliac
      disease in vivo. METHODS: Four adults with coeliac disease, all of whom were on a
      gluten free diet, underwent three challenges. Peptic-tryptic gliadin (PTG 1 g)
      served as a positive control. The test peptide and a negative control peptide
      were studied on separate occasions. The peptides were instilled into the duodenum
      and biopsies were taken before the infusion, and two, four, and six hours after
      commencing the infusions, using a Quinton hydraulic multiple biopsy capsule.
      Biopsy specimens were assessed blindly for villus height to crypt depth ratio
      (VH:CD), enterocyte cell height (ECH), and intraepithelial lymphocyte (IEL)
      count. We used the Mann-Whitney U test, with 95% confidence intervals, for
      statistical analysis. RESULTS: VH:CD and ECH fell, and IEL increased
      significantly 4-6 hours after commencing infusions with both PTG and the test
      peptide in all subjects. The negative control peptide caused no significant
      changes to villus morphology, enterocyte height, or IEL count in any patient.
      CONCLUSION: We have confirmed that the putative immunodominant epitope, a peptide
      corresponding to residues 56-75 of alpha-gliadins, exacerbates coeliac disease in
      vivo.

PMID- 14633946
TI  - Familial aggregation of irritable bowel syndrome: a prospective study.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) often report family
      members with similar symptoms, but family studies are lacking. We hypothesised
      that if there is familial aggregation, there would be an increased frequency of
      IBS in first degree relatives of IBS patients compared with relatives of controls
      (the patient's spouse). METHODS: A valid self report bowel disease questionnaire
      (BDQ) that recorded symptoms, the somatic symptom checklist (a measure of
      somatisation), and a family information form (FIF) to collect the names and
      addresses of all first degree relatives were mailed to two groups of patients and
      their spouses (patients attending an IBS educational programme and residents of
      Olmsted County, Minnesota, who had been coded as IBS on a database). A BDQ was
      then mailed to all first degree relatives of subjects identified from the FIF.
      IBS diagnosis in the relatives was based on the Manning criteria. RESULTS: The
      BDQ was sent to a total of 355 eligible relatives; 71% responded (73% relatives
      of patients, 67% relatives of spouses). Relatives were comparable in mean age,
      sex distribution, and somatisation score. IBS prevalence was 17% in patients'
      relatives versus 7% in spouses' relatives (odds ratio adjusted for age and sex
      2.7 (95% confidence interval (CI) 1.2, 6.3)). When also adjusted for somatisation
      score, the odds ratio was reduced to 2.5 (95% CI 0.9, 6.7). CONCLUSIONS: Familial
      aggregation of IBS occurs, supporting a genetic or intrafamilial environment
      component, but this may be explained in part by familial aggregation of
      somatisation.

PMID- 14633947
TI  - Intestinal gas distribution determines abdominal symptoms.
AB  - BACKGROUND: Patients with functional gut disorders manifest poor tolerance to
      intestinal gas loads but the mechanism of this dysfunction is unknown. AIM: Our
      aims were firstly, to explore the relative importance of the amount of intestinal
      gas versus its distribution on symptom production, and secondly, to correlate gut
      motility and perception of gas loads. SUBJECTS: Fourteen healthy subjects with no
      gastrointestinal symptoms. METHODS: In each subject a gas mixture was infused (12
      ml/min) either into the jejunum or rectum for one hour during blocked rectal gas
      outflow, and subsequently gas clearance was measured over one hour of free rectal
      evacuation. We measured abdominal perception, distension, and gut tone by
      duodenal and rectal barostats. RESULTS: Similar magnitude of gas retention (720
      ml) produced significantly more abdominal symptoms with jejunal compared with
      rectal infusion (perception score 4.4 (0.4) v 1.5 (0.5), respectively; p<0.01)
      whereas abdominal distension was similar (15 (2) mm and 14 (1) mm girth
      increment, respectively). Jejunal gas loads were associated with proximal
      contraction (by 57 (5)%) and colonic loads with distal relaxation (by 99 (20)%).
      CONCLUSION: The volume of gas within the gut determines abdominal distension
      whereas symptom perception depends on intraluminal gas distribution and possibly
      also on the gut motor response to gas loads.

PMID- 14633948
TI  - Cyclooxygenase 2 mediates post-inflammatory colonic secretory and barrier
      dysfunction.
AB  - BACKGROUND AND AIMS: The colonic epithelium plays a key role in host defence.
      During colitis, epithelial function is impaired, leading to elevated bacterial
      translocation and exacerbation of inflammation. We previously documented
      perturbation of epithelial function, in terms of secretion and as a barrier to
      bacterial translocation, that persisted long after resolution of a bout of
      colitis in the rat. The mechanisms underlying the epithelial dysfunction are not
      completely understood. METHODS: Given the ability of prostaglandin (PG) D2 to
      suppress colonic epithelial secretion, we investigated the potential roles of
      this eicosanoid and of cyclooxygenase 2 (COX-2) in mediating post-colitis
      epithelial secretory and barrier dysfunction. RESULTS: Six weeks after induction
      of colitis with trinitrobenzene sulphonic acid, there was marked elevated
      synthesis of PGD2 and elevated COX-2 expression. Selective COX-2 inhibition
      abolished the increase in PGD2 synthesis. Colonic chloride secretory responses
      (in vitro) were significantly diminished relative to those in controls, a defect
      that was reversed by pre-exposure to a selective COX-2 inhibitor (celecoxib) but
      not to a selective COX-1 inhibitor (SC-560). The hyporesponsiveness was mimicked
      by pre-exposure of normal colonic tissue to PGD2, but not to its metabolite, 15
      deoxy-Delta(12-14)PGJ2. The post-colitis rats exhibited a 10-fold increase in
      bacterial colonisation of the colon, and >3-fold increase in bacterial
      translocation. Twice daily treatment for one week with a selective COX-2
      inhibitor (rofecoxib) did not affect bacterial colonisation but abolished the
      increase in bacterial translocation. CONCLUSIONS: These studies demonstrate an
      important role for COX-2, possibly via generation of PGD2, in mediating the
      prolonged epithelial secretory and barrier dysfunction after a bout of colitis in
      the rat.

PMID- 14633950
TI  - Fever, night sweats, and a hepatic mass.

PMID- 14633949
TI  - Antibiotics with a selective aerobic or anaerobic spectrum have different
      therapeutic activities in various regions of the colon in interleukin 10 gene
      deficient mice.
AB  - BACKGROUND AND AIMS: Multiple rodent models implicate resident intestinal
      bacteria in the pathogenesis of chronic immune mediated intestinal inflammation.
      Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10(-/-)) mice
      develop colitis, which does not occur in the germ free (GF) state. We
      investigated whether broad or narrow spectrum antibiotics affect onset and
      progression of disease in various regions of IL-10(-/-) mice. METHODS:
      Metronidazole, ciprofloxacin, vancomycin-imipenem (50 mg/kg/day), or water
      (control) was administered orally before (prevention) or two weeks after
      (treatment) colonisation of GF IL-10(-/-) mice with SPF bacteria. After four
      weeks, colonic histology scores and cytokine production by colonic explants were
      determined. Caecal and colonic contents were collected for quantitative bacterial
      analysis. RESULTS: In the prevention study, all antibiotics decreased
      inflammation in the caecum and colon. However, in the treatment study,
      ciprofloxacin and vancomycin-imipenem decreased caecal inflammation, and reduced
      Escherichia coli and Enterococcus faecalis concentrations, whereas only
      vancomycin-imipenem lowered direct microscopic bacterial counts. In contrast,
      metronidazole and vancomycin-imipenem reduced colonic injury and eliminated
      anaerobic bacteria, including Bacteroides spp. CONCLUSIONS: Both narrow and broad
      spectrum antibiotics can prevent disease but treatment of established colitis is
      more selective. Ciprofloxacin is most effective in the treatment of caecal
      inflammation, metronidazole preferentially treats the colon, whereas vancomycin
      imipenem definitively treats both regions. These results suggest that subsets of
      aerobic or anaerobic bacteria show regional differences in their capacity to
      mediate experimental colitis in IL-10(-/-) mice.

PMID- 14633951
TI  - A randomised placebo controlled trial of pegylated interferon alpha in active
      ulcerative colitis.
AB  - BACKGROUND: Pilot studies of interferon alpha (IFN-alpha) suggest a high
      remission rate in the treatment of active ulcerative colitis. We evaluated the
      safety of pegylated interferon alpha (PegIFN) and its role in induction of
      remission in patients with active ulcerative colitis, in a multicentre placebo
      controlled trial. METHODS: Sixty patients with a clinical activity score (CAI) of
      >6 were randomised to receive placebo (n=20), PegIFN 0.5 microg/kg (n=19), or
      PegIFN 1.0 microg/kg body weight (n=21) once weekly (PegIntron; Schering-Plough,
      USA) over 12 weeks. Patients receiving 5-aminosalicylates, steroids, and/or
      azathioprine in stable dosages were included. RESULTS: Serious adverse events
      were seen in none of the placebo patients, in 3/19 patients in the PegIFN 0.5
      microg/kg group (hospitalisation due to disease flare up n=3), and in 3/21 in the
      PegIFN 1.0 microg/kg group (hospitalisation due to disease flare up n=1;
      thrombosis n=1; grand mal seizure n=1). Otherwise, we observed only minor IFN
      alpha side effects. Clinical remission rates at week 12 (CAI < or =4) were 7/20
      (35%) in the placebo, 9/19 (47%) in the PegIFN 0.5 microg/kg group, and 7/21
      (33%) in the PegIFN 1.0 microg/kg group (NS). Early withdrawal from the study was
      observed in 11/20 placebo patients, in 6/19 in the PegIFN 0.5 microg/kg group,
      and in 10/21 in the PegIFN 1.0 microg/kg group, mainly due to lack of efficacy.
      The higher PegIFN dose was associated with a significant decrease in levels of C
      reactive protein (p=0.003, day 0 v 85). CONCLUSIONS: PegIFN is safe but not
      effective, at the dosages used, in patients with ulcerative colitis.

PMID- 14633952
TI  - Do calcium channel blockers and antimuscarinics protect against perforated
      colonic diverticular disease? A case control study.
AB  - BACKGROUND: The aetiology of perforated colonic diverticular disease (PCDD)
      remains largely unknown. Perforation may result from a combination of high
      intracolonic pressures, secondary to excessive colonic segmentation, and
      impairment of the mucosal barrier. Calcium channel blockers and antimuscarinic
      drugs, which reduce colonic contractility and tone, could potentially protect
      against perforation. The aim of this study was to test this hypothesis using a
      case control design. METHODS: All cases of acute PCDD were identified over a five
      year period in two hospitals in Norfolk, UK. Each case was matched for age, sex,
      and date of admission to two controls groups: (1) patients undergoing cataract
      surgery and (2) patients with basal cell carcinoma. Data on drug use prior to
      hospital admission were obtained from medical and nursing records and compared
      between cases and controls. RESULTS: A total of 120 cases of PCDD were identified
      and matched to 240 controls in each group. A statistically significant protective
      association was seen between calcium channel blocker use and PCDD using both
      control groups. The odds ratios were 0.41 (95% confidence interval (CI) 0.18
      0.93) using the ophthalmology control group and 0.36 (95% CI 0.16-0.82) using the
      dermatology control group. CONCLUSIONS: This study has shown for the first time
      that a protective association exists between calcium channel blockers and PCDD.
      The validity of this association is supported by the consistent finding in both
      control groups and the plausible biological mechanisms. Further studies are
      required to confirm this association but calcium channel blockers may represent a
      potential preventive therapy in PCDD.

PMID- 14633953
TI  - Dark lumen magnetic resonance colonography: comparison with conventional
      colonoscopy for the detection of colorectal pathology.
AB  - BACKGROUND: The purpose of this study was to assess the feasibility and
      usefulness of a new magnetic resonance (MR) colonography technique for the
      detection of colorectal pathology in comparison with conventional colonoscopy as
      the standard of reference. PATIENTS AND METHODS: A total of 122 subjects with
      suspected colorectal disease underwent "dark lumen" MR colonography. A contrast
      enhanced T1w three dimensional VIBE sequence was collected after rectal
      administration of water. The presence of colorectal masses and inflammatory
      lesions were documented. Results were compared with those of a subsequently
      performed colonoscopy. RESULTS: MR colonography was found to be accurate
      regarding detection of clinically relevant colonic lesions exceeding 5 mm in
      size, with sensitivity and specificity values of 93%/100%. CONCLUSION: Dark lumen
      MR colonography can be considered as a promising alternative method for the
      detection of colorectal disease. In addition, it allows assessment of
      extraluminal organs.

PMID- 14633954
TI  - Extracolonic findings at computed tomography colonography are a challenge.
AB  - AIM: Our aim was to perform a prospective evaluation of the frequency and
      diagnostic consequences of extracolonic findings at multidetector array computed
      tomography colonography (MDCTC) in asymptomatic patients undergoing surveillance
      for former colorectal polyps or cancer. PATIENTS AND METHODS: Seventy five
      consecutive patients undergoing surveillance for former colorectal cancer (CRC)
      or large bowel adenoma were examined with MDCTC. Two independent observers
      evaluated the images with regard to extracolonic findings. Patient records and
      radiological information systems were reviewed to determine the results and
      consequences of the workup derived from MDCTC. RESULTS: Sixty five per cent (95%
      confidence interval (CI) 55-73%) of patients had extracolonic abnormalities and
      in 12% (CI 7-18%) of patients additional workup was indicated. Two patients (3%
      (CI 1-6%)) underwent surgery because of the findings (one) or because of
      complications of the workup (one). CONCLUSION: MDCTC identifies a large number of
      extracolonic findings. Approximately 12% of asymptomatic patients undergo
      additional workup, of benefit to only a few. The high prevalence of extracolonic
      findings may make MDCTC a problematic colorectal screening tool for both ethical
      and economic reasons.

PMID- 14633955
TI  - Colonoscopy surveillance of individuals at risk of familial colorectal cancer.
AB  - BACKGROUND: Individuals with first degree relatives affected with colorectal
      cancer (CRC) at a young age, or more than one relative affected but who do not
      fulfil the Amsterdam criteria for a diagnosis of hereditary non-polyposis colon
      cancer (HNPCC), are believed to be at an increased risk of CRC. However, there is
      a paucity of prospective data on the potential benefit of colonoscopic
      surveillance in such groups categorised by empiric family history criteria. We
      report a prospective study of 448 individuals seeking counselling about their
      perceived family history of CRC. PATIENTS AND METHODS: Following pedigree
      tracing, verification, and risk assignment by genetic counsellors, colonoscopy
      was undertaken for those at a moderate or high risk (HNPCC). Those classified as
      low risk were reassured and discharged without surveillance. Here we report our
      findings at the prevalence screen in the 176 patients of the 448 assessed who
      underwent colonoscopy. RESULTS: Fifty three individuals had a family history that
      met Amsterdam criteria (median age 43 years) and 123 individuals were classed as
      moderate risk (median age 43 years). No cancers were detected at colonoscopy in
      any group. Four individuals (8% (95% confidence limits (CL) 0.4-15%)) in the high
      risk group had an adenoma detected at a median age of 46 years and all four were
      less than 50 years of age. Five (4% (95% CL 0.6- 8%)) of the moderate risk
      individuals had an adenoma at a median age of 54 years, two of whom were less
      than 50 years of age. CONCLUSIONS: These findings indicate that the prevalence of
      significant neoplasia in groups defined by family history is low, particularly in
      younger age groups. These prospective data call into question the value of
      colonoscopy before the age of 50 years in moderate risk individuals.

PMID- 14633956
TI  - Decision analysis in the surgical treatment of colorectal cancer due to a
      mismatch repair gene defect.
AB  - BACKGROUND: In view of the high risk of developing a new primary colorectal
      carcinoma (CRC), subtotal colectomy rather than segmental resection or
      hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal
      cancer (HNPCC) patients. Subtotal colectomy however implies a substantial
      decrease in quality of life. To date, colonoscopic surveillance has been shown to
      reduce CRC occurrence. AIMS: To compare the potential health effects in terms of
      life expectancy (LE) for patients undergoing subtotal colectomy or hemicolectomy
      for CRC. METHODS: A decision analysis (Markov) model was created. Information on
      the 10 year risk of CRC after subtotal colectomy (4%) and hemicolectomy (16%) and
      stages of CRCs detected within a two year surveillance interval (32% Dukes' A,
      54% Dukes' B, and 14% Dukes' C) were derived from two cohort studies. Five year
      survival rates used for the different Dukes stages (A, B, and C) were 98%, 80%,
      and 60%, respectively. Remaining LE values were calculated for hypothetical
      cohorts with an age at CRC diagnosis of 27, 47, and 67 years, respectively.
      Remaining LE values were also calculated for patients with CRC of Dukes' stage A.
      RESULTS: The overall LE gain of subtotal colectomy compared with hemicolectomy at
      ages 27, 47, and 67 was 2.3, 1, and 0.3 years, respectively. Specifically for
      Dukes' stage A, this would be 3.4, 1.5, and 0.4 years. CONCLUSIONS: Unless
      surveillance results improve, subtotal colectomy still seems the preferred
      treatment for CRC in HNPCC in view of the difference in LE. For older patients,
      hemicolectomy may be an option as there is no appreciable difference in LE.

PMID- 14633957
TI  - Prognostic significance of the allelic loss of the BRCA1 gene in colorectal
      cancer.
AB  - BACKGROUND: Survival at the intermediate stage of colorectal cancer (CRC) is less
      predictable than in the early and advanced stages. Several genetic markers
      possibly involved in growth and progression of CRC can be used for prognosis.
      AIMS: This study investigated the proportion of allelic loss (loss of
      heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient
      prognosis. PATIENTS AND METHODS: A total of 314 patients were investigated for
      LOH at the BRCA1 locus using polymerase chain reaction by means of three
      intragenic polymorphic microsatellite markers. Allelic losses were compared with
      clinicopathological characteristics of patients, recurrence rate, disease free
      survival (DFS), and overall survival. RESULTS: Twenty six patients were excluded
      because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%)
      were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was
      higher in patients with LOH (p=0.0003), and DFS was 73.3% (SEM 5.7) at five years
      in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss
      (p=0.0004). Retention of alleles at the BRCA1 locus was associated with a
      favourable DFS in stages I and II (p<0.05). The presence of LOH was also
      significantly associated with short overall survival (p=0.02). Multivariate
      analysis in the complete series showed that stage (p=0.006) and lymph node
      metastases (> or =4 nodes, p=0.0001; 1-3 nodes, p=0.038) were independent
      prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH
      was an independent prognostic factor in stages I and II (p=0.001). CONCLUSIONS:
      BRCA1 LOH is a molecular alteration present in CRC, with unfavourable
      repercussions for overall survival, that could be considered as an outstanding
      independent prognostic factor in stages I and II.

PMID- 14633958
TI  - Abnormal vascular network complexity: a new phenotypic marker in hereditary non
      polyposis colorectal cancer syndrome.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer
      family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary
      cancer disorders. HNPCC results from dominantly inherited germline mutations in
      mismatch repair (MMR) genes, leading to genomic instability and cancer. No
      predictive physical signs of HNPCC are available to date. AIMS: Increased
      complexity in tumour associated vascular growth has been reported. Here, we
      tested the hypothesis that an increased vascular network complexity is a
      phenotypic marker for LCFS2. METHODS: Fourteen subjects from an LCFS2 kindred
      (gene carriers, n=5; non-carriers, n=9) and 30 controls were examined. Fractal
      dimension (D) at two scales (D (1-46), and D (1-15), tortuosity (minimum path
      dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular
      networks from the lower gingival and vestibular oral mucosa were measured.
      RESULTS: LCFS2 networks exhibited a significantly increased overall complexity at
      both larger (D (1-46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1
      15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured
      randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel
      tortuosity (DMIN: 1.02 (0.03) v 1.07 (0.04); p=0.0005) compared with control
      patterns. The vascular networks of LCFS2 gene carriers showed higher complexity
      at the smaller scale (D (1-15): 1.59 (0.12) v 1.47 (0.07); p=0.034), and higher
      destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p=0.013) than those of
      non-carriers. CONCLUSIONS: Increased oral vascular network complexity is a
      previously unrecognised phenotypic marker for LCFS2, and is related to gene
      mutation carrier status.

PMID- 14633959
TI  - Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces
      the incidence of pancreatitis associated with therapeutic endoscopic retrograde
      cholangiopancreatography procedures: a randomised controlled trial.
AB  - BACKGROUND: Previous studies suggested that somatostatin given before endoscopic
      retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP
      pancreatitis. However, the routine use of somatostatin in all patients undergoing
      ERCP is not likely to be cost effective. This study evaluated whether intravenous
      bolus somatostatin given after diagnostic cholangiopancreatography could reduce
      the incidence of pancreatitis in a group of patients undergoing therapeutic ERCP
      procedures. METHODS: In a randomised, double blind, controlled trial, the effect
      of intravenous bolus somatostatin 250 microg given immediately after diagnostic
      cholangiopancreatography was compared with that of placebo in patients who
      required endoscopic sphincterotomy or other therapeutic procedures. The primary
      end point was the incidence of post-ERCP clinical pancreatitis, and a secondary
      end point was the incidence of hyperamylasemia. RESULTS: A total of 270 patients
      were randomised. The somatostatin group (n=135) and the placebo group (n=135)
      were comparable in age, sex, indications for treatment, and types of procedure.
      The frequencies of clinical pancreatitis (4.4% v 13.3%; p=0.010) and
      hyperamylasemia (26.0% v 38.5%; p=0.036) were both significantly lower in the
      somatostatin group compared with the placebo group. CONCLUSIONS: A single dose of
      intravenous bolus somatostatin, given immediately after diagnostic
      cholangiopancreatography, is effective in reducing the incidence of pancreatitis
      after therapeutic ERCP. This novel approach of administering prophylactic
      somatostatin may offer a cost effective prophylaxis for post-ERCP pancreatitis.

PMID- 14633961
TI  - Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes.
AB  - BACKGROUND AND AIMS: Hydrophobic bile acids contribute to hepatocellular injury
      in cholestasis and rapidly induce apoptosis in vitro; however, unlike Fas
      agonists, cholestasis does not cause extensive hepatocyte apoptosis. As
      antioxidants provide protection against bile acid induced liver injury, our
      premise was that bilirubin, a free radical scavenger with increased plasma levels
      in the presence of liver disease, could protect hepatocytes against bile acid
      induced apoptosis. METHODS: Freshly isolated rat hepatocytes were incubated for
      four hours with 100 micromol/l glycochenodeoxycholate (GCDC) alone or with
      increasing concentrations of unconjugated (UCB) or conjugated (CB) bilirubin.
      RESULTS: Both UCB and CB inhibited GCDC induced apoptosis in a dose dependent
      fashion and suppressed the generation of reactive oxygen species by hepatocytes.
      CONCLUSIONS: The antiapoptotic effect of bilirubin associated with its
      antioxidant properties indicates that hyperbilirubinaemia may have a protective
      role in liver disease.

PMID- 14633962
TI  - Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a
      predictive factor for post-treatment relapse after lamivudine induced hepatitis B
      e antigen loss or seroconversion.
AB  - BACKGROUND AND AIMS: Lamivudine induces favourable virological and biochemical
      responses but post-treatment relapses are frequent, even in patients with
      hepatitis B e antigen (HBeAg) loss or seroconversion. The aim of this study was
      to determine whether extended lamivudine therapy for up to 12 months after HBeAg
      loss/seroconversion could decrease the risk of post-treatment virological
      relapse. In addition, we monitored serum hepatitis B virus (HBV) DNA levels using
      a quantitative polymerase chain reaction (PCR) assay during extended lamivudine
      therapy and analysed predictive factors for post-treatment relapse. PATIENTS AND
      METHODS: A total of 49 patients who exhibited HBeAg loss/seroconversion during
      lamivudine therapy received extended lamivudine therapy for six months (group 1,
      n=23) or 12 months (group 2, n=26) after HBeAg loss/seroconversion. Serum HBV DNA
      levels were quantified by a PCR based assay at the time of HBeAg
      loss/seroconversion, and at cessation of therapy. RESULTS: Post-treatment
      virological relapse rates at two years were 59% in group 1 and 50% in group 2.
      Age, time interval to HBeAg loss/seroconversion, and serum HBV DNA levels at the
      time of cessation of therapy were independent predictive factors for post
      treatment relapse. The post-treatment relapse rate was 37% at two years in
      patients with serum HBV DNA levels of <200 copies/ml but 73% in those with > or
      =10(3) copies/ml. CONCLUSIONS: Extended lamivudine therapy for up to 12 months
      did not decrease the rate of post-treatment virological relapse, and monitoring
      of serum HBV DNA by a quantitative PCR method was helpful in predicting post
      treatment relapse.

PMID- 14633963
TI  - Treatment of hepatitis C. The 2002 French consensus.

PMID- 14633966
TI  - High magnification chromoscopic colonoscopy as a screening tool in acromegaly.

PMID- 14633964
TI  - ABC of oral bioavailability: transporters as gatekeepers in the gut.
AB  - MDR1 (ABCB1), MRP2 (ABCC2), and BCRP (ABCG2) are members of the family of ATP
      binding cassette (ABC) transporters. These are plasma membrane transporters that
      are expressed in various organs. The role of MDR1 and MRP2 in the hepatobiliary
      system is well defined; both contribute to bile formation by transport of drugs,
      toxins, and waste products across the canalicular membrane. As they transport
      exogenous and endogenous substances, they reduce the body load of potentially
      harmful compounds. The role of ABCG2, which is also expressed in the canalicular
      membrane of hepatocytes, has not yet been fully characterised. All three proteins
      are also expressed in the apical membrane of enterocytes where they probably
      control oral availability of many substances. This important "gatekeeper"
      function of ABC transporters has been recognised recently and is currently under
      further investigation. Expression and activity of these transporters in the gut
      may differ between individuals, due to genetic polymorphisms or pathological
      conditions. This will lead to individual differences in bioavailability of
      different drugs, toxins, and (food derived) carcinogens. Recent information on
      substrates, transport mechanisms, function, and regulation of expression of MDR1,
      MRP2, and BCRP in different species is summarised in this review.

PMID- 14633968
TI  - Fetal "cardiac mucosa" is not adult cardiac mucosa.

PMID- 14633969
TI  - Platelet activation in patients with irritable bowel syndrome may reflect a
      subclinical inflammatory response.

PMID- 14633970
TI  - Helicobacter pylori infection in Africa and Europe: enigma of host genetics.

PMID- 14633971
TI  - Structural and biochemical analyses of DNA and RNA binding by a bifunctional
      homing endonuclease and group I intron splicing factor.
AB  - We determined the crystal structure of a bifunctional group I intron splicing
      factor and homing endonuclease, termed the I-AniI maturase, in complex with its
      DNA target at 2.6 A resolution. The structure demonstrates the remarkable
      structural conservation of the beta-sheet DNA-binding motif between highly
      divergent enzyme subfamilies. DNA recognition by I-AniI was further studied using
      nucleoside deletion and DMS modification interference analyses. Correlation of
      these results with the crystal structure provides information on the relative
      importance of individual nucleotide contacts for DNA recognition. Alignment and
      modeling of two homologous maturases reveals conserved basic surface residues,
      distant from the DNA-binding surface, that might be involved in RNA binding. A
      point mutation that introduces a single negative charge in this region uncouples
      the maturase and endonuclease functions of the protein, inhibiting RNA binding
      and splicing while maintaining DNA binding and cleavage.

PMID- 14633972
TI  - Hierarchical assembly of the budding yeast kinetochore from multiple
      subcomplexes.
AB  - Kinetochores are multiprotein complexes that assemble on centromeric DNA and
      attach chromosomes to spindle microtubules. Over the past six years, the number
      of proteins known to localize to the Saccharomyces cerevisiae kinetochore has
      increased from around 10 to over 60. However, relatively little is known about
      the protein-protein interactions that mediate kinetochore assembly or about the
      overall structure of microtubule-attachment sites. Here we used biophysical
      techniques, affinity purification, mass spectrometry, and in vivo assays to
      examine the state of association of 31 centromere-binding proteins, including six
      proteins newly identified as kinetochore subunits. We found that yeast
      kinetochores resemble transcriptional enhancers in being composed of at least 17
      discrete subcomplexes that assemble on DNA to form a very large structure with a
      mass in excess of 5 MD. Critical to kinetochore assembly are proteins that bridge
      subunits in direct contact with DNA and subunits bound to microtubules. We show
      that two newly identified kinetochore complexes, COMA (Ctf19p-Okp1p-Mcm21p-Ame1p)
      and MIND (Mtw1p including Nnf1p-Nsl1p-Dsn1p) function as bridges. COMA, MIND, and
      the previously described Ndc80 complex constitute three independent and essential
      platforms onto which outer kinetochore proteins assemble. In addition, we propose
      that the three complexes have different functions with respect to force
      generation and MT attachment.

PMID- 14633973
TI  - Ecsit is required for Bmp signaling and mesoderm formation during mouse
      embryogenesis.
AB  - Bone morphogenetic proteins (Bmps) are members of the transforming growth factor
      beta (TGFbeta) superfamily that play critical roles during mouse embryogenesis.
      Signaling by Bmp receptors is mediated mainly by Smad proteins. In this study, we
      show that a targeted null mutation of Ecsit, encoding a signaling intermediate of
      the Toll pathway, leads to reduced cell proliferation, altered epiblast
      patterning, impairment of mesoderm formation, and embryonic lethality at
      embryonic day 7.5 (E7.5), phenotypes that mimic the Bmp receptor type1a (Bmpr1a)
      null mutant. In addition, specific Bmp target gene expression is abolished in the
      absence of Ecsit. Biochemical analysis demonstrates that Ecsit associates
      constitutively with Smad4 and associates with Smad1 in a Bmp-inducible manner.
      Together with Smad1 and Smad4, Ecsit binds to the promoter of specific Bmp target
      genes. Finally, knock-down of Ecsit with Ecsit-specific short hairpin RNA
      inhibits both Bmp and Toll signaling. Therefore, these results show that Ecsit
      functions as an essential component in two important signal transduction pathways
      and establishes a novel role for Ecsit as a cofactor for Smad proteins in the Bmp
      signaling pathway.

PMID- 14633974
TI  - tRNAHis maturation: an essential yeast protein catalyzes addition of a guanine
      nucleotide to the 5' end of tRNAHis.
AB  - All tRNAHis molecules are unusual in having an extra 5' GMP residue (G(-1)) that,
      in eukaryotes, is added after transcription and RNase P cleavage. Incorporation
      of this G(-1) residue is a rare example of nucleotide addition occurring at an
      RNA 5' end in a normal phosphodiester linkage. We show here that the essential
      Saccharomyces cerevisiae ORF YGR024c (THG1) is responsible for this
      guanylyltransferase reaction. Thg1p was identified by survey of a genomic
      collection of yeast GST-ORF fusion proteins for addition of [alpha-32P]GTP to
      tRNAHis. End analysis confirms the presence of G(-1). Thg1p is required for
      tRNAHis guanylylation in vivo, because cells depleted of Thg1p lack G(-1) in
      their tRNAHis. His6-Thg1p purified from Escherichia coli catalyzes the
      guanylyltransferase step of G(-1) addition using a ppp-tRNAHis substrate, and
      appears to catalyze the activation step using p-tRNAHis and ATP. Thg1p is highlye
      conserved in eukaryotes, where G(-1) addition is necessary, and is not found in
      eubacteria, where G(-1) is genome-encoded. Thus, Thg1p is the first member of a
      new family of enzymes that can catalyze phosphodiester bond formation at the 5'
      end of RNAs, formally in a 3'-5' direction. Surprisingly, despite its varied
      activities, Thg1p contains no recognizable catalytic or functional domains.

PMID- 14633975
TI  - DNA damage response and MCL-1 destruction initiate apoptosis in adenovirus
      infected cells.
AB  - Expression of adenovirus E1A deregulates cell proliferation to facilitate viral
      DNA replication, prompting the initiation of apoptosis signaled primarily through
      proapoptotic BAK in productively infected cells. We demonstrate here that in
      uninfected cells, BAK is complexed with the anti-apoptotic BCL-2 family member
      Myeloid Cell Leukemia 1 (MCL-1). E1A expression during infection resulted in the
      specific down-regulation of MCL-1 through destabilization of the protein and loss
      of the mRNA. Upon loss of the MCL-1-BAK complex, BAK complexed with either BAX in
      proapoptotic E1B mutant adenovirus-infected cells, or with the adenovirus BCL-2
      homolog E1B 19K in cells infected with the wild-type virus in which apoptosis is
      inhibited. Loss of MCL-1 was required to initiate the apoptotic pathway in
      infected cells as restoration of MCL-1 expression rescued infected cells from E1A
      induced apoptosis. Analogous to E1A expression, DNA damage down-regulates MCL-1,
      and adenovirus infection resulted in the accumulation of phosphorylated H2AX and
      ataxia-telangiectasia mutant protein (ATM), hallmarks of DNA double-strand
      breaks. Thus, MCL-1 may function by maintaining BAK in an inactive state, and the
      loss of MCL-1 upon activation of the DNA damage response, perhaps through
      replication stress induced in virus infected cells, may be required to initiate
      the apoptotic response.

PMID- 14633976
TI  - Human placental growth hormone increases expression of the p85 regulatory unit of
      phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal
      muscle.
AB  - The insulin resistance of normal pregnancy is necessary to divert fuels to the
      fetus to meet fetal growth demands and is mediated by placental hormones. We
      recently demonstrated that human placental GH (hPGH) can trigger severe insulin
      resistance in transgenic (TG) mice. In this study we sought to elucidate the
      cellular mechanisms by which hPGH interferes with insulin signaling in muscle in
      TG mice. Insulin-stimulated GLUT-4 translocation to the plasma membrane (PM) was
      reduced in the TG compared with wild-type (WT) mice (P = 0.05). Insulin receptor
      (IR) levels were modestly reduced by 19% (P < 0.01) in TG mice, but there were no
      changes in phosphorylation of IR or IR substrate-1 (IRS-1) between WT and TG
      mice. A singular finding was a highly significant increase in the p85 alpha
      regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase; P < 0.001), yet
      a reduced ability of insulin to stimulate IRS-1-associated PI 3-kinase activity
      (P < 0.05). Although the levels of the p110 catalytic subunit protein of PI 3
      kinase and IRS-1 were unchanged in the TG mice, insulin's ability to stimulate
      p110 association with IRS-1 was markedly reduced (P < 0.0001). We demonstrate a
      unique mechanism of insulin resistance and suggest that hPGH may contribute to
      the insulin resistance of normal pregnancy by increasing the expression of the
      p85 alpha monomer, which competes in a dominant negative fashion with the p85
      p110 heterodimer for binding to IRS-1 protein.

PMID- 14633977
TI  - Three-dimensional structure of the bacterial multidrug transporter EmrE shows it
      is an asymmetric homodimer.
AB  - The small multidrug resistance family of transporters is widespread in bacteria
      and is responsible for bacterial resistance to toxic aromatic cations by proton
      linked efflux. We have determined the three-dimensional (3D) structure of the
      Escherichia coli multidrug transporter EmrE by electron cryomicroscopy of 2D
      crystals, including data to 7.0 A resolution. The structure of EmrE consists of a
      bundle of eight transmembrane alpha-helices with one substrate molecule bound
      near the centre. The substrate binding chamber is formed from six helices and is
      accessible both from the aqueous phase and laterally from the lipid bilayer. The
      most remarkable feature of the structure of EmrE is that it is an asymmetric
      homodimer. The possible arrangement of the two polypeptides in the EmrE dimer is
      discussed based on the 3D density map.

PMID- 14633978
TI  - Structure of the mitochondrial ATP synthase by electron cryomicroscopy.
AB  - We have determined the structure of intact ATP synthase from bovine heart
      mitochondria by electron cryomicroscopy of single particles. Docking of an atomic
      model of the F1-c10 subcomplex into a major segment of the map has allowed the 32
      A resolution density to be interpreted as the F1-ATPase, a central and a
      peripheral stalk and an FO membrane region that is composed of two domains. One
      domain of FO corresponds to the ring of c-subunits, and the other probably
      contains the a-subunit, the transmembrane portion of the b-subunit and the
      remaining integral membrane proteins of FO. The peripheral stalk wraps around the
      molecule and connects the apex of F1 to the second domain of FO. The interaction
      of the peripheral stalk with F1-c10 implies that it binds to a non-catalytic
      alpha-beta interface in F1 and its inclination where it is not attached to F1
      suggests that it has a flexible region that can serve as a stator during both ATP
      synthesis and ATP hydrolysis.

PMID- 14633979
TI  - Structural constraints on protein self-processing in L-aspartate-alpha
      decarboxylase.
AB  - Aspartate decarboxylase, which is translated as a pro-protein, undergoes
      intramolecular self-cleavage at Gly24-Ser25. We have determined the crystal
      structures of an unprocessed native precursor, in addition to Ala24 insertion,
      Ala26 insertion and Gly24-->Ser, His11-->Ala, Ser25-->Ala, Ser25-->Cys and Ser25-
      >Thr mutants. Comparative analyses of the cleavage site reveal specific
      conformational constraints that govern self-processing and demonstrate that
      considerable rearrangement must occur. We suggest that Thr57 Ogamma and a water
      molecule form an 'oxyanion hole' that likely stabilizes the proposed
      oxyoxazolidine intermediate. Thr57 and this water molecule are probable catalytic
      residues able to support acid-base catalysis. The conformational freedom in the
      loop preceding the cleavage site appears to play a determining role in the
      reaction. The molecular mechanism of self-processing, presented here, emphasizes
      the importance of stabilization of the oxyoxazolidine intermediate. Comparison of
      the structural features shows significant similarity to those in other self
      processing systems, and suggests that models of the cleavage site of such enzymes
      based on Ser-->Ala or Ser-->Thr mutants alone may lead to erroneous
      interpretations of the mechanism.

PMID- 14633980
TI  - Large T antigen on the simian virus 40 origin of replication: a 3D snapshot prior
      to DNA replication.
AB  - Large T antigen is the replicative helicase of simian virus 40. Its specific
      binding to the origin of replication and oligomerization into a double hexamer
      distorts and unwinds dsDNA. In viral replication, T antigen acts as a functional
      homolog of the eukaryotic minichromosome maintenance factor MCM. T antigen is
      also an oncoprotein involved in transformation through interaction with p53 and
      pRb. We obtained the three-dimensional structure of the full-length T antigen
      double hexamer assembled at its origin of replication by cryoelectron microscopy
      and single-particle reconstruction techniques. The double hexamer shows different
      degrees of bending along the DNA axis. The two hexamers are differentiated
      entities rotated relative to each other. Isolated strands of density, putatively
      assigned to ssDNA, protrude from the hexamer-hexamer junction mainly at two
      opposite sites. The structure of the T antigen at the origin of replication can
      be understood as a snapshot of the dynamic events leading to DNA unwinding. Based
      on these results a model for the initiation of simian virus 40 DNA replication is
      proposed.

PMID- 14633981
TI  - Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of
      Radical SAM enzymes.
AB  - 'Radical SAM' enzymes generate catalytic radicals by combining a 4Fe-4S cluster
      and S-adenosylmethionine (SAM) in close proximity. We present the first crystal
      structure of a Radical SAM enzyme, that of HemN, the Escherichia coli oxygen
      independent coproporphyrinogen III oxidase, at 2.07 A resolution. HemN catalyzes
      the essential conversion of coproporphyrinogen III to protoporphyrinogen IX
      during heme biosynthesis. HemN binds a 4Fe-4S cluster through three cysteine
      residues conserved in all Radical SAM enzymes. A juxtaposed SAM coordinates the
      fourth Fe ion through its amide nitrogen and carboxylate oxygen. The SAM
      sulfonium sulfur is near both the Fe (3.5 A) and a neighboring sulfur of the
      cluster (3.6 A), allowing single electron transfer from the 4Fe-4S cluster to the
      SAM sulfonium. SAM is cleaved yielding a highly oxidizing 5'-deoxyadenosyl
      radical. HemN, strikingly, binds a second SAM immediately adjacent to the first.
      It may thus successively catalyze two propionate decarboxylations. The structure
      of HemN reveals the cofactor geometry required for Radical SAM catalysis and sets
      the stage for the development of inhibitors with antibacterial function due to
      the uniquely bacterial occurrence of the enzyme.

PMID- 14633982
TI  - Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase.
AB  - Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the
      heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups
      of uroporphyrinogen to form coproporphyrinogen. Here we report crystal structures
      of URO-D in complex with the I and III isomer coproporphyrinogen products.
      Crystallization required use of a novel enzymatic approach to generate the highly
      oxygen-sensitive porphyrinogen substrate in situ. The tetrapyrrole product adopts
      a domed conformation that lies against a collar of conserved hydrophobic residues
      and allows formation of hydrogen bonding interactions between a carboxylate
      oxygen atom of the invariant Asp86 residue and the pyrrole NH groups. Structural
      and biochemical analyses of URO-D proteins mutated at Asp86 support the
      conclusion that this residue makes important contributions to binding and likely
      promotes catalysis by stabilizing a positive charge on a reaction intermediate.
      The central coordination geometry of Asp86 allows the initial substrates and the
      various partially decarboxylated intermediates to be bound with equivalent
      activating interactions, and thereby explains how all four of the substrate
      acetate groups can be decarboxylated at the same catalytic center.

PMID- 14633983
TI  - The phosphorylation state of an autoregulatory domain controls PACS-1-directed
      protein traffic.
AB  - PACS-1 is a cytosolic sorting protein that directs the localization of membrane
      proteins in the trans-Golgi network (TGN)/endosomal system. PACS-1 connects the
      clathrin adaptor AP-1 to acidic cluster sorting motifs contained in the
      cytoplasmic domain of cargo proteins such as furin, the cation-independent
      mannose-6-phosphate receptor and in viral proteins such as human immunodeficiency
      virus type 1 Nef. Here we show that an acidic cluster on PACS-1, which is highly
      similar to acidic cluster sorting motifs on cargo molecules, acts as an
      autoregulatory domain that controls PACS-1-directed sorting. Biochemical studies
      show that Ser278 adjacent to the acidic cluster is phosphorylated by CK2 and
      dephosphorylated by PP2A. Phosphorylation of Ser278 by CK2 or a Ser278-->Asp
      mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-
      >Ala substitution decreased this interaction. Moreover, the Ser278-->Ala mutation
      yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of
      PACS-1-regulated cargo molecules to the TGN. These results suggest that
      coordinated signaling events regulate transport within the TGN/endosomal system
      through the phosphorylation state of both cargo and the sorting machinery.

PMID- 14633984
TI  - Switch from capsid protein import to adenovirus assembly by cleavage of nuclear
      transport signals.
AB  - Replication and assembly of adenovirus occurs in the nucleus of infected cells,
      requiring the nuclear import of all viral structural proteins. In this report we
      show that nuclear import of the major capsid protein, hexon, is mediated by
      protein VI, a structural protein located underneath the 12 vertices of the
      adenoviral capsid. Our data indicate that protein VI shuttles between the nucleus
      and the cytoplasm and that it links hexon to the nuclear import machinery via an
      importin alpha/beta-dependent mechanism. Key nuclear import and export signals of
      protein VI are located in a short C-terminal segment, which is proteolytically
      removed during virus maturation. The removal of these C-terminal transport
      signals appears to trigger a functional transition in protein VI, from a role in
      supporting hexon nuclear import to a structural role in virus assembly.

PMID- 14633985
TI  - RNA-binding protein Csx1 mediates global control of gene expression in response
      to oxidative stress.
AB  - Fission yeast Spc1 (Sty1), a stress-activated mitogen-activated protein kinase
      (MAPK) homologous to human p38, orchestrates global changes in gene expression in
      response to diverse forms of cytotoxic stress. This control is partly mediated
      through Atf1, a transcription factor homologous to human ATF2. How Spc1 controls
      Atf1, and how the cells tailor gene expression patterns to different forms of
      stress, are unknown. Here we describe Csx1, a novel protein crucial for survival
      of oxidative but not osmotic stress. Csx1 associates with and stabilizes atf1+
      mRNA in response to oxidative stress. Csx1 controls expression of the majority of
      the genes induced by oxidative stress, including most of the genes regulated by
      Spc1 and Atf1. These studies reveal a novel mechanism controlling MAPK-regulated
      transcription factors and suggest how gene expression patterns can be customized
      to specific forms of stress. Csx1-like proteins in humans may perform similar
      tasks.

PMID- 14633986
TI  - Osteocyte control of bone formation via sclerostin, a novel BMP antagonist.
AB  - There is an unmet medical need for anabolic treatments to restore lost bone.
      Human genetic bone disorders provide insight into bone regulatory processes.
      Sclerosteosis is a disease typified by high bone mass due to the loss of SOST
      expression. Sclerostin, the SOST gene protein product, competed with the type I
      and type II bone morphogenetic protein (BMP) receptors for binding to BMPs,
      decreased BMP signaling and suppressed mineralization of osteoblastic cells. SOST
      expression was detected in cultured osteoblasts and in mineralizing areas of the
      skeleton, but not in osteoclasts. Strong expression in osteocytes suggested that
      sclerostin expressed by these central regulatory cells mediates bone homeostasis.
      Transgenic mice overexpressing SOST exhibited low bone mass and decreased bone
      strength as the result of a significant reduction in osteoblast activity and
      subsequently, bone formation. Modulation of this osteocyte-derived negative
      signal is therapeutically relevant for disorders associated with bone loss.

PMID- 14633987
TI  - Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling.
AB  - The cytokines IL-1 and TNF induce expression of a series of genes that regulate
      inflammation through activation of NF-kappaB signal transduction pathways. TAK1,
      a MAPKKK, is critical for both IL-1- and TNF-induced activation of the NF-kappaB
      pathway. TAB2, a TAK1-binding protein, is involved in IL-1-induced NF-kappaB
      activation by physically linking TAK1 to TRAF6. However, IL-1-induced activation
      of NF-kappaB is not impaired in TAB2-deficient embryonic fibroblasts. Here we
      report the identification and characterization of a novel protein designated
      TAB3, a TAB2-like molecule that associates with TAK1 and can activate NF-kappaB
      similar to TAB2. Endogenous TAB3 interacts with TRAF6 and TRAF2 in an IL-1- and a
      TNF-dependent manner, respectively. Further more, IL-1 signaling leads to the
      ubiquitination of TAB2 and TAB3 through TRAF6. Cotransfection of siRNAs directed
      against both TAB2 and TAB3 inhibit both IL-1- and TNF-induced activation of TAK1
      and NF-kappaB. These results suggest that TAB2 and TAB3 function redundantly as
      mediators of TAK1 activation in IL-1 and TNF signal transduction.

PMID- 14633988
TI  - E2F7, a novel E2F featuring DP-independent repression of a subset of E2F
      regulated genes.
AB  - The E2F family of transcription factors play an essential role in the regulation
      of cell cycle progression. In a screen for E2F-regulated genes we identified a
      novel E2F family member, E2F7. Like the recently identified E2F-like proteins of
      Arabidopsis, E2F7 has two DNA binding domains and binds to the E2F DNA binding
      consensus site independently of DP co-factors. Consistent with being an E2F
      target gene, we found that the expression of E2F7 is cell cycle regulated.
      Ectopic expression of E2F7 results in suppression of E2F target genes and
      accumulation of cells in G1. Furthermore, E2F7 associates with E2F-regulated
      promoters in vivo, and this association increases in S phase. Interestingly,
      however, E2F7 binds only a subset of E2F-dependent promoters in vivo, and in
      agreement with this, inhibition of E2F7 expression results in specific
      derepression of these promoters. Taken together, these data demonstrate that E2F7
      is a unique repressor of a subset of E2F target genes whose products are required
      for cell cycle progression.

PMID- 14633989
TI  - Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the
      parathyroid hormone gene.
AB  - The human AP-endonuclease (APE1/Ref-1), a multifunctional protein central to
      repairing abasic sites and single-strand breaks in DNA, also plays a role in
      transcriptional regulation. Besides activating some transcription factors, APE1
      is directly involved in Ca2+-dependent downregulation of parathyroid hormone
      (PTH) expression by binding to negative calcium response elements (nCaREs)
      present in the PTH promoter. Here we show that APE1 is acetylated both in vivo
      and in vitro by the transcriptional co-activator p300 which is activated by Ca2+.
      Acetylation at Lys6 or Lys7 enhances binding of APE1 to nCaRE. APE1 stably
      interacts with class I histone deacetylases (HDACs) in vivo. An increase in
      extracellular calcium enhances the level of acetylated APE1 which acts as a
      repressor for the PTH promoter. Moreover, chromatin immunoprecipitation (ChIP)
      assay revealed that acetylation of APE1 enhanced binding of the APE1-HDACs
      complex to the PTH promoter. These results indicate that acetylation of APE1
      plays an important role in this key repair protein's action in transcriptional
      regulation.

PMID- 14633990
TI  - NRSF regulates the fetal cardiac gene program and maintains normal cardiac
      structure and function.
AB  - Reactivation of the fetal cardiac gene program is a characteristic feature of
      hypertrophied and failing hearts that correlates with impaired cardiac function
      and poor prognosis. However, the mechanism governing the reversible expression of
      fetal cardiac genes remains unresolved. Here we show that neuron-restrictive
      silencer factor (NRSF), a transcriptional repressor, selectively regulates
      expression of multiple fetal cardiac genes, including those for atrial
      natriuretic peptide, brain natriuretic peptide and alpha-skeletal actin, and
      plays a role in molecular pathways leading to the re-expression of those genes in
      ventricular myocytes. Moreover, transgenic mice expressing a dominant-negative
      mutant of NRSF in their hearts exhibit dilated cardiomyopathy, high
      susceptibility to arrhythmias and sudden death. We demonstrate that genes
      encoding two ion channels that carry the fetal cardiac currents I(f) and I(Ca,T),
      which are induced in these mice and are potentially responsible for both the
      cardiac dysfunction and the arrhythmogenesis, are regulated by NRSF. Our results
      indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene
      program and suggest an important role for NRSF in maintaining normal cardiac
      structure and function.

PMID- 14633991
TI  - Transcript cleavage factors GreA and GreB act as transient catalytic components
      of RNA polymerase.
AB  - Prokaryotic transcription elongation factors GreA and GreB stimulate intrinsic
      nucleolytic activity of RNA polymerase (RNAP). The proposed biological role of
      Gre-induced RNA hydrolysis includes transcription proofreading, suppression of
      transcriptional pausing and arrest, and facilitation of RNAP transition from
      transcription initiation to transcription elongation. Using an array of
      biochemical and molecular genetic methods, we mapped the interaction interface
      between Gre and RNAP and identified the key residues in Gre responsible for
      induction of nucleolytic activity in RNAP. We propose a structural model in which
      the C-terminal globular domain of Gre binds near the opening of the RNAP
      secondary channel, the N-terminal coiled-coil domain (NTD) protrudes inside the
      RNAP channel, and the tip of the NTD is brought to the immediate vicinity of RNAP
      catalytic center. Two conserved acidic residues D41 and E44 located at the tip of
      the NTD assist RNAP by coordinating the Mg2+ ion and water molecule required for
      catalysis of RNA hydrolysis. If so, Gre would be the first transcription factor
      known to directly participate in the catalytic act of RNAP.

PMID- 14633992
TI  - Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in
      human cancer.
AB  - Methyl-CpG binding proteins (MBDs) mediate histone deacetylase-dependent
      transcriptional silencing at methylated CpG islands. Using chromatin
      immunoprecitation (ChIP) we have found that gene-specific profiles of MBDs exist
      for hypermethylated promoters of breast cancer cells, whilst a common pattern of
      histone modifications is shared. This unique distribution of MBDs is also
      characterized in chromosomes by comparative genomic hybridization of
      immunoprecipitated DNA and immunolocalization. Most importantly, we demonstrate
      that MBD association to methylated DNA serves to identify novel targets of
      epigenetic inactivation in human cancer. We combined the ChIP assay of MBDs with
      a CpG island microarray (ChIP on chip). The scenario revealed shows that, while
      many genes are regulated by multiple MBDs, others are associated with a single
      MBD. These target genes displayed methylation- associated transcriptional
      silencing in breast cancer cells and primary tumours. The candidates include the
      homeobox gene PAX6, the prolactin hormone receptor, and dipeptidylpeptidase IV
      among others. Our results support an essential role for MBDs in gene silencing
      and, when combined with genomic strategies, their potential to 'catch' new
      hypermethylated genes in cancer.

PMID- 14633993
TI  - FinO is an RNA chaperone that facilitates sense-antisense RNA interactions.
AB  - The protein FinO represses F-plasmid conjugative transfer by facilitating
      interactions between the mRNA of the major F-plasmid transcriptional activator,
      TraJ, and an antisense RNA, FinP. FinO is known to bind stem-loop structures in
      both FinP and traJ RNAs; however, the mechanism by which FinO facilitates sense
      antisense pairing is poorly understood. Here we show that FinO acts as an RNA
      chaperone to promote strand exchange and duplexing between minimal RNA targets
      derived from FinP. This strongly suggests that FinO may function to destabilize
      internal secondary structures within FinP and traJ RNAs that would otherwise act
      as a kinetic trap to sense-antisense pairing. The energy for FinO-catalyzed base
      pair destabilization does not arise from ATP hydrolysis but appears to be
      supplied directly from FinO RNA binding free energy. An analysis of the
      activities of mutants that are specifically deficient in strand exchange but not
      RNA-binding activity demonstrates that strand exchange is essential to the
      ability of FinO to mediate sense-antisense RNA recognition, and that this
      function also plays a role in repression of conjugation in vivo.

PMID- 14633994
TI  - The PTB interacting protein raver1 regulates alpha-tropomyosin alternative
      splicing.
AB  - Regulated switching of the mutually exclusive exons 2 and 3 of alpha-tropomyosin
      (TM) involves repression of exon 3 in smooth muscle cells. Polypyrimidine tract
      binding protein (PTB) is necessary but not sufficient for regulation of TM
      splicing. Raver1 was identified in two-hybrid screens by its interactions with
      the cytoskeletal proteins actinin and vinculin, and was also found to interact
      with PTB. Consistent with these interactions raver1 can be localized in either
      the nucleus or cytoplasm. Here we show that raver1 is able to promote the smooth
      muscle-specific alternative splicing of TM by enhancing PTB-mediated repression
      of exon 3. This activity of raver1 is dependent upon characterized PTB-binding
      regulatory elements and upon a region of raver1 necessary for interaction with
      PTB. Heterologous recruitment of raver1, or just its C-terminus, induced very
      high levels of exon 3 skipping, bypassing the usual need for PTB binding sites
      downstream of exon 3. This suggests a novel mechanism for PTB-mediated splicing
      repression involving recruitment of raver1 as a potent splicing co-repressor.

PMID- 14633995
TI  - MDM2 promotes p21waf1/cip1 proteasomal turnover independently of ubiquitylation.
AB  - The CDK inhibitor p21waf1/cip1 is degraded by a ubiquitin-independent proteolytic
      pathway. Here, we show that MDM2 mediates this degradation process.
      Overexpression of wild-type or ring finger-deleted, but not nuclear localization
      signal (NLS)-deleted, MDM2 decreased p21waf1/cip1 levels without ubiquitylating
      this protein and affecting its mRNA level in p53(-/-) cells. This decrease was
      reversed by the proteasome inhibitors MG132 and lactacystin, by p19(arf), and by
      small interfering RNA (siRNA) against MDM2. p21waf1/cip1 bound to MDM2 in vitro
      and in cells. The p21waf1/cip1-binding-defective mutant of MDM2 was unable to
      degrade p21waf1/cip1. MDM2 shortened the half-life of both exogenous and
      endogenous p21waf1/cip1 by 50% and led to the degradation of its lysine-free
      mutant. Consequently, MDM2 suppressed p21waf1/cip1-induced cell growth arrest of
      human p53(-/-) and p53(-/-)/Rb(-/-)cells. These results demonstrate that MDM2
      directly inhibits p21waf1/cip1 function by reducing p21waf1/cip1 stability in a
      ubiquitin-independent fashion.

PMID- 14633996
TI  - Tab2 is a novel conserved RNA binding protein required for translation of the
      chloroplast psaB mRNA.
AB  - The chloroplast psaB mRNA encodes one of the reaction centre polypeptides of
      photosystem I. Protein pulse-labelling profiles indicate that the mutant strain
      of Chlamydomonas reinhardtii, F14, affected at the nuclear locus TAB2, is
      deficient in the translation of psaB mRNA and thus deficient in photosystem I
      activity. Genetic studies reveal that the target site for Tab2 is situated within
      the psaB 5'UTR. We have used genomic complementation to isolate the nuclear Tab2
      gene. The deduced amino acid sequence of Tab2 (358 residues) displays 31-46%
      sequence identity with several orthologues found only in eukaryotic and
      prokaryotic organisms performing oxygenic photosynthesis. Directed mutagenesis
      indicates the importance of a highly conserved C-terminal tripeptide in Tab2 for
      normal psaB translation. The Tab2 protein is localized in the chloroplast stroma
      where it is associated with a high molecular mass protein complex containing the
      psaB mRNA. Gel mobility shift assays reveal a direct and specific interaction
      between Tab2 and the psaB 5'UTR. We propose that Tab2 plays a key role in the
      initial steps of PsaB translation and photosystem I assembly.

PMID- 14633997
TI  - YaeL proteolysis of RseA is controlled by the PDZ domain of YaeL and a Gln-rich
      region of RseA.
AB  - sigmaE is an alternative sigma factor involved in a pathway of extracytoplasmic
      stress responses in Escherichia coli. Under normal growth conditions, sigmaE
      activity is down-regulated by the membrane-bound anti-sigmaE protein, RseA.
      Extracytoplasmic stress signals induce degradation of RseA by two successive
      proteolytic events: DegS-catalyzed first cleavage at a periplasmic site followed
      by YaeL-mediated second proteolysis at an intramembrane region. Normally, the
      second reaction (site-2 proteolysis) only occurs after the first cleavage (site-1
      cleavage). Here, we show that YaeL variants with the periplasmic PDZ domain
      deleted or mutated allows unregulated cleavage of RseA and consequent sigmaE
      activation. It was also found that a glutamine-rich region in the periplasmic
      domain of RseA was required for the avoidance of the YaeL-mediated proteolysis in
      the absence of site-1 cleavage. These results indicate that multiple negative
      elements both in the enzyme (PDZ domain) and in the substrate (glutamine-rich
      region) determine the strict dependence of the site-2 proteolysis on the site-1
      cleavage.

PMID- 14633998
TI  - Decatenation of DNA circles by FtsK-dependent Xer site-specific recombination.
AB  - DNA replication results in interlinked (catenated) sister duplex molecules as a
      consequence of the intertwined helices that comprise duplex DNA. DNA
      topoisomerases play key roles in decatenation. We demonstrate a novel, efficient
      and directional decatenation process in vitro, which uses the combination of the
      Escherichia coli XerCD site-specific recombination system and a protein, FtsK,
      which facilitates simple synapsis of dif recombination sites during its
      translocation along DNA. We propose that the FtsK-XerCD recombination machinery,
      which converts chromosomal dimers to monomers, may also function in vivo in
      removing the final catenation links remaining upon completion of DNA replication.

PMID- 14634000
TI  - Regulated conformation of myosin V.
AB  - We have found that myosin V, an important actin-based vesicle transporter, has a
      folded conformation that is coupled to inhibition of its enzymatic activity in
      the absence of cargo and Ca(2+). In the absence of Ca(2+) where the actin
      activated MgATPase activity is low, purified brain myosin V sediments in the
      analytical ultracentrifuge at 14 S as opposed to 11 S in the presence of Ca(2+)
      where the activity is high. At high ionic strength it sediments at 10 S
      independent of Ca(2+), and its regulation is poor. These data are consistent with
      myosin V having a compact, inactive conformation in the absence of Ca(2+) and an
      extended conformation in the presence of Ca(2+) or high ionic strength. Electron
      microscopy reveals that in the absence of Ca(2+) the heads and tail are both
      folded to give a triangular shape, very different from the extended appearance of
      myosin V at high ionic strength. A recombinant myosin V heavy meromyosin fragment
      that is missing the distal portion of the tail domain is not regulated by calcium
      and has only a small change in sedimentation coefficient, which is in the
      opposite direction to that seen with intact myosin V. Electron microscopy shows
      that its heads are extended even in the absence of calcium. These data suggest
      that interaction between the motor and cargo binding domains may be a general
      mechanism for shutting down motor protein activity and thereby regulating the
      active movement of vesicles in cells.

PMID- 14633999
TI  - Competitive processivity-clamp usage by DNA polymerases during DNA replication
      and repair.
AB  - Protein clamps are ubiquitous and essential components of DNA metabolic
      machineries, where they serve as mobile platforms that interact with a large
      variety of proteins. In this report we identify residues that are required for
      binding of the beta-clamp to DNA polymerase III of Escherichia coli, a polymerase
      of the Pol C family. We show that the alpha polymerase subunit of DNA polymerase
      III interacts with the beta-clamp via its extreme seven C-terminal residues, some
      of which are conserved. Moreover, interaction of Pol III with the clamp takes
      place at the same site as that of the delta-subunit of the clamp loader,
      providing the basis for a switch between the clamp loading machinery and the
      polymerase itself. Escherichia coli DNA polymerases I, II, IV and V (UmuC)
      interact with beta at the same site. Given the limited amounts of clamps in the
      cell, these results suggest that clamp binding may be competitive and regulated,
      and that the different polymerases may use the same clamp sequentially during
      replication and repair.

PMID- 14634001
TI  - Kruppel-like factors regulate the Lama1 gene encoding the laminin alpha1 chain.
AB  - Laminin-1 (alpha1beta1gamma1), a basement membrane (BM) constituent, has been
      associated with differentiation processes and also with malignant progression. In
      the intestinal tissue, the alpha1 chain is expressed and secreted in the
      subepithelial BM during the developmental period; in the adult rodent tissue, it
      is restricted to the BM of the dividing cells. To understand how laminin alpha1
      chain expression is regulated, we cloned and characterized a 2-kb promoter region
      of the Lama1 mouse gene. Analysis of the promoter was conducted in the Caco2-TC7
      intestinal epithelial cells by transient transfection of serially deleted and
      site-directed mutated promoter constructs, by electrophoretic mobility shift
      assays, and expression of selected transcription factors. We determined that a
      proximal region, which includes an Sp1-binding GC box and a Kruppel-like element,
      was important for the promoter activity. This region is conserved between the
      human and mouse genes. Interestingly, two Kruppel-like factors KLF4 and KLF5
      exhibit opposing effects on the Lama1 promoter activity that are decreased and
      increased, respectively, in the intestinal epithelial cells. These data
      corroborate the complementary expression of KLF4 and KLF5 along the intestinal
      crypt-villus axis and the parallel expression of KLF5 and laminin alpha1 chain in
      the crypt region. Finally, we showed that glucocorticoids stimulate the promoter
      activity. This study is the first characterization of the Lama1 promoter; we
      identified regulatory elements that may account for the expression pattern of the
      endogenous protein in the mouse intestine.

PMID- 14634002
TI  - Selective contribution of eukaryotic prefoldin subunits to actin and tubulin
      binding.
AB  - Eukaryotic prefoldin (PFD) is a heterohexameric chaperone with a jellyfish-like
      structure whose function is to deliver nonnative target proteins, principally
      actins and tubulins, to the eukaryotic cytosolic chaperonin for facilitated
      folding. Here we demonstrate that functional PFD can spontaneously assemble from
      its six constituent individual subunits (PFD1-PFD6), each expressed as a
      recombinant protein. Using engineered forms of PFD assembled in vitro, we show
      that the tips of the PFD tentacles are required to form binary complexes with
      authentic target proteins. We show that PFD uses the distal ends of different but
      overlapping sets of subunits to form stable binary complexes with different
      target proteins, namely actin and alpha- and beta-tubulin. We also present data
      that suggest a model for the order of these six subunits within the hexamer. Our
      data are consistent with the hypothesis that PFD, like the eukaryotic cytosolic
      chaperonin, has co-evolved specifically to facilitate the folding of its target
      proteins.

PMID- 14634003
TI  - The three-dimensional structure of the cardiac L-type voltage-gated calcium
      channel: comparison with the skeletal muscle form reveals a common architectural
      motif.
AB  - We describe here the first three-dimensional structure of the cardiac L-type
      voltage-gated calcium channel (VGCC) purified from bovine heart. The structure
      was determined by electron microscopy and single particle analysis of negatively
      stained complexes, using the angular reconstitution method. The cardiac VGCC can
      be isolated as a stable dimer, as reported previously for the skeletal muscle
      VGCC, with a central aqueous chamber formed by the two halves of the complex.
      Moreover, we demonstrate that the dimeric cardiac VGCC binds the dihydropyridine
      [3H]azidopine with a Kd approximately 310 pM. We have compared the cardiac VGCC
      structure with the skeletal muscle form, determined using the same reconstructive
      methodology, allowing us to identify common and distinct features of the
      complexes. By using antibody and lectin-gold labeling, we have localized the
      intracellular beta polypeptides and the extracellular glycosylation sites of the
      skeletal muscle VGCC, which can be correlated to the cardiac three-dimensional
      structure. From the data presented here the assignment of the orientation of the
      VGCC complexes with respect to the lipid bilayer is now possible. A difference
      between the cardiac and skeletal muscle ion channels is apparent in the putative
      transmembrane region, which would be consistent with the absence of the gamma
      subunit in the cardiac VGCC assembly.

PMID- 14634004
TI  - Vascular smooth muscle polyploidization as a biomarker for aging and its impact
      on differential gene expression.
AB  - Polyploidy is characterized by a greater than diploid content of DNA in a cell.
      Previous measurements of ploidy level in different organs of humans and rodents,
      including the aorta, indicated an increase in old versus young. We hypothesized
      that aortic vascular smooth muscle polyploidy is a biomarker for aging and that
      the augmented DNA dosage affects selective gene-specific transcript expression.
      Our results demonstrate that tetraploidy increases exponentially over the life
      span of the animal, serving as an indicator of age. Approximately 60% of the
      vascular smooth muscle cells in the thoracic aorta of 36-month-old Brown Norway
      rats are tetraploid compared with 8% in their 3-month-old counterparts.
      Microarray analysis and reverse transcriptase-PCR was performed with mRNA
      isolated from sorted diploid (2N) and tetraploid (4N) vascular smooth muscle
      cells from old rats to identify differentially expressed transcripts. For the
      majority of detectable transcripts, an increase in DNA content led to a
      proportional increase in mRNA. A select group of transcripts, however, were
      reduced in tetraploid compared with diploid cells. These mRNAs correspond to
      guanine deaminase, to the matrix proteins rat glypican 3 (OCI-5) and decorin, as
      well as to the inflammation-associated transcripts, insulin-like growth factor
      binding protein 6, macrophage inflammatory protein 2 precursor, macrophage
      galactose N-acetylgalactoseamine-specific lectin, and complement component C4.
      Our study is the first to describe aortic ploidy level as a biomarker for aging
      and to indicate that changes associated with increased DNA content per cell may
      selectively suppress the expression of specific genes.

PMID- 14634005
TI  - The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of
      the Sry-related high mobility group box gene, Sox18.
AB  - VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular
      development. VCAM-1 is an important adhesion molecule that is expressed on
      endothelial cells and has a critical role in endothelial activation,
      inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high
      mobility group box factor Sox18 has previously been implicated in endothelial
      pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and
      lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal
      patterns of expression, which is suggestive of cross-talk. We use biochemical
      techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with
      a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an
      important target of Sox18. Transfection, site-specific mutagenesis, and gel shift
      analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1
      expression. Importantly, the naturally occurring Sox18 mutant attenuates the
      expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation
      of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals
      show a dramatic and significant reduction in VCAM-1 mRNA expression in lung,
      skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important
      target of SOX18 provides the first molecular insights into the vascular
      abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedema
      telangiectasia disorder.

PMID- 14634006
TI  - Direct regulation of microtubule dynamics by protein kinase CK2.
AB  - Microtubule dynamics is essential for many vital cellular processes such as
      morphogenesis and motility. Protein kinase CK2 is a ubiquitous protein kinase
      that is involved in diverse cellular functions. CK2 holoenzyme is composed of two
      catalytic alpha or alpha' subunits and two regulatory beta subunits. We show that
      the alpha subunit of CK2 binds directly to both microtubules and tubulin
      heterodimers. CK2 holoenzyme but neither of its individual subunits exhibited a
      potent effect of inducing microtubule assembly and bundling. Moreover, the
      polymerized microtubules were strongly stabilized by CK2 against cold-induced
      depolymerization. Interestingly, the kinase activity of CK2 is not required for
      its microtubule-assembling and stabilizing function because a kinase-inactive
      mutant of CK2 displayed the same microtubule-assembling activity as the wild-type
      protein. Knockdown of CK2alpha/alpha' in cultured cells by RNA interference
      dramatically destabilized their microtubule networks, and the destabilized
      microtubules were readily destructed by colchicine at a very low concentration.
      Further, over-expression of chicken CK2alpha or its kinaseinactive mutant in the
      endogenous CK2alpha/alpha'-depleted cells fully restored the microtubule
      resistance to the low dose of colchicine. Taken together, CK2 is a microtubule
      associated protein that confers microtubule stability in a phosphorylation
      independent manner.

PMID- 14634007
TI  - Crystal structure of the E2 transactivation domain of human papillomavirus type
      11 bound to a protein interaction inhibitor.
AB  - Interaction between the E2 protein and E1 helicase of human papillomaviruses
      (HPVs) is essential for the initiation of viral DNA replication. We recently
      described a series of small molecules that bind to the N-terminal transactivation
      domain (TAD) of HPV type 11 E2 and inhibits its interaction with E1 in vitro and
      in cellular assays. Here we report the crystal structures of both the HPV11 TAD
      and of a complex between this domain and an inhibitor, at 2.5- and 2.4-A
      resolution, respectively. The HPV11 TAD structure is very similar to that of the
      analogous domain of HPV16. Inhibitor binding caused no significant alteration of
      the protein backbone, but movements of several amino acid side chains at the
      binding site, in particular those of Tyr-19, His-32, Leu-94, and Glu-100,
      resulted in the formation of a deep hydrophobic pocket that accommodates the
      indandione moiety of the inhibitor. Mutational analysis provides functional
      evidence for specific interactions between Tyr-19 and E1 and between His-32 and
      the inhibitor. A second inhibitor molecule is also present at the binding pocket.
      Although evidence is presented that this second molecule makes only weak
      interactions with the protein and is likely an artifact of crystallization, its
      presence defines additional regions of the binding pocket that could be exploited
      to design more potent inhibitors.

PMID- 14634008
TI  - Mutations in a conserved motif inhibit single-stranded DNA binding and
      recombination mediator activities of bacteriophage T4 UvsY protein.
AB  - The UvsY recombination mediator protein is critical for homologous recombination
      in bacteriophage T4. UvsY uses both protein-protein and protein-DNA interactions
      to mediate the assembly of the T4 UvsX recombinase onto single-stranded (ss) DNA,
      forming presynaptic filaments that initiate DNA strand exchange. UvsY helps UvsX
      compete with Gp32, the T4 ssDNA-binding protein, for binding sites on ssDNA, in
      part by destabilizing Gp32-ssDNA interactions, and in part by stabilizing UvsX
      ssDNA interactions. The relative contributions of UvsY-ssDNA, UvsY-Gp32, UvsY
      UvsX, and UvsY-UvsY interactions to these processes are only partially
      understood. The goal of this study was to isolate mutant forms of UvsY protein
      that are specifically defective in UvsY-ssDNA interactions, so that the
      contribution of this activity to recombination processes could be assessed
      independent of other factors. A conserved motif of UvsY found in other DNA
      binding proteins was targeted for mutagenesis. Two missense mutants of UvsY were
      isolated in which ssDNA binding activity is compromised. These mutants retain
      self-association activity, and form stable associations with UvsX and Gp32
      proteins in patterns similar to wild-type UvsY. Both mutants are partially, but
      not totally, defective in stimulating UvsX-catalyzed recombination functions
      including ssDNA-dependent ATP hydrolysis and DNA strand exchange. The data are
      consistent with a model in which UvsY plays bipartite roles in presynaptic
      filament assembly. Its protein-ssDNA interactions are suggested to moderate the
      destabilization of Gp32-ssDNA, whereas its protein-protein contacts induce a
      conformational change of the UvsX protein, giving UvsX a higher affinity for the
      ssDNA and allowing it to compete more effectively with Gp32 for binding sites.

PMID- 14634009
TI  - Gamma-glutamyltranspeptidase stimulates receptor activator of nuclear factor
      kappaB ligand expression independent of its enzymatic activity and serves as a
      pathological bone-resorbing factor.
AB  - A novel bone-resorbing factor was cloned using an expression cloning technique,
      which involved a Xenopus oocyte expression system and an assay for osteoclast
      formation. A candidate clone was isolated from a BW5147 mouse T-lymphoma cell
      cDNA library. Sequencing analysis identified the factor as gamma
      glutamyltranspeptidase (GGT), which is an enzyme involved in glutathione
      metabolism. The addition of purified GGT protein to mouse bone marrow culture
      effectively induced formation of osteoclasts. An antibody against GGT inhibited
      osteoclast formation but not the enzymatic activity. We also demonstrated that an
      inactive form of GGT, the enzymatic activity of which had been blocked by
      chemical modification with a specific inhibitor, acivicin, supported osteoclast
      formation. These results indicate that GGT acts on osteoclast formation
      independent of its own enzymatic activity. Furthermore, both native GGT and
      inactive GGT stimulated the expression of the receptor activator of nuclear
      factor-kappaB ligand (RANKL) mRNA and protein from bone marrow stromal cells.
      This report is the first demonstration of a novel biological activity of GGT
      protein in a manner independent of its enzymatic activity.

PMID- 14634010
TI  - Modulation of prion protein oligomerization, aggregation, and beta-sheet
      conversion by 4,4'-dianilino-1,1'-binaphthyl-5,5'-sulfonate (bis-ANS).
AB  - The prion protein (PrP) is the major agent implicated in the diseases known as
      transmissible spongiform encephalopathies. The onset of transmissible spongiform
      encephalopathy is related to a change in conformation of the PrP(C), which loses
      most of its alpha-helical content, becoming a beta-sheet-rich protein, known as
      PrP(Sc). Here we have used two Syrian hamster prion domains (PrP 109-141 and PrP
      109-149) and the murine recombinant PrP (rPrP 23-231) to investigate the effects
      of anilino-naphtalene compounds on prion oligomerization and aggregation.
      Aggregation in the presence of bis-ANS (4,4'-dianilino-1,1'-binaphthyl-5,5'
      sulfonate), ANS (1-anilinonaphthalene-8-sulfonate), and AmNS (1-amino-5
      naphtalenesulfonate) was monitored. Bis-ANS was the most effective inhibitor of
      prion peptide aggregation. Bis-ANS binds strongly to rPrP 23-231 leading to a
      substantial increase in beta-sheet content and to limited oligomerization. More
      strikingly, the binding of bis-ANS to full-length rPrP is diminished by the
      addition of nanomolar concentrations of oligonucleotides, demonstrating that they
      compete for the same binding site. Thus, bis-ANS displays properties similar to
      those of nucleic acids, causing oligomerization and conversion to beta-sheet
      (Cordeiro, Y., Machado, F., Juliano, L., Juliano, M. A., Brentani, R. R., Foguel,
      D., and Silva, J. L. (2001) J. Biol. Chem. 276, 49400-49409). This dual effect of
      bis-ANS on prion protein makes this compound highly important to sequester
      crucial conformations of the protein, which may be useful to the understanding of
      the disease and to serve as a lead for the development of new therapeutic
      strategies.

PMID- 14634011
TI  - Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heart
      specific lipoprotein lipase transgenic mouse.
AB  - Lipid accumulation is associated with cardiac dysfunction in diabetes and
      obesity. Transgenic mice expressing non-transferable lipoprotein lipase (LpL)
      with a glycosylated phosphatidyl-inositol (GPI) anchor in cardiomyocytes have
      dilated cardiomyopathy. However, the mechanisms responsible for lipid
      accumulation and cardiomyopathy are not clear. Hearts from 3-month-old mice
      expressing GPI-anchored human LpL (hLpLGPI) mice had increased fatty acid
      oxidation and heart failure genes and decreased glucose transporter genes. 6
      month-old mice had increased mRNA expression and activation of the apoptosis
      marker caspase-3. Moreover, hLpLGPI hearts had significant cytochrome c release
      from mitochondria to cytosol. Low density lipoprotein uptake was greater in
      hLpLGPI hearts, and this was associated with more intracellular apolipoprotein B
      (apoB). To test whether lipid accumulation in the hLpLGPI heart is reduced by
      cardiac expression of apoB, hLpLGPI mice were bred with transgenic human apoB
      (HuB)-expressing mice. Hearts of HuB/hLpLGPI mice had less triglyceride (38%) and
      free fatty acids (19%), secreted more apoB, and expressed less atrial natriuretic
      factor (ANF) and brain natriuretic peptide (BNP) and more glucose transporter 4
      (GLUT4). The increased mortality of the mice was abrogated by the transgenic
      expression of apoB. Therefore, we hypothesize that cardiac apoB expression
      improves cardiomyopathy by increasing lipid resecretion from the heart.

PMID- 14634012
TI  - Parathyroid hormone induction of the osteocalcin gene. Requirement for an
      osteoblast-specific element 1 sequence in the promoter and involvement of
      multiple-signaling pathways.
AB  - Parathyroid hormone (PTH) is an important peptide hormone regulator of bone
      formation and osteoblast activity. However, its mechanism of action in bone cells
      is largely unknown. This study examined the effect of PTH on mouse osteocalcin
      gene expression in MC3T3-E1 preosteoblastic cells and primary cultures of bone
      marrow stromal cells. PTH increased the levels of osteocalcin mRNA 4-5-fold in
      both cell types. PTH also stimulated transcriptional activity of a 1.3-kb
      fragment of the mouse osteocalcin gene 2 (mOG2) promoter. Inhibitor studies
      revealed a requirement for protein kinase A, protein kinase C, and mitogen
      activated protein kinase pathways in the PTH response. Deletion of the mOG2
      promoter sequence from -1316 to -116 caused no loss in PTH responsiveness whereas
      deletion from -116 to -34 completely prevented PTH stimulation. Interestingly,
      this promoter region does not contain the RUNX2 binding site shown to be
      necessary for PTH responsiveness in other systems. Nuclear extracts from PTH
      treated MC3T3-E1 cells exhibited increased binding to OSE1, a previously
      described osteoblast-specific enhancer in the mOG2 promoter. Furthermore,
      mutation of OSE1 in DNA transfection assays established the requirement for this
      element in the PTH response. Collectively, these studies establish that actions
      of PTH on the osteocalcin gene are mediated by multiple signaling pathways and
      require OSE1 and associated nuclear proteins.

PMID- 14634013
TI  - DNA recognition by the homing endonuclease PI-SceI involves a divalent metal ion
      cofactor-induced conformational change.
AB  - PI-SceI, a homing endonuclease of the LAGLIDADG family, consists of two domains
      involved in DNA cleavage and protein splicing, respectively. Both domains
      cooperate in binding the recognition sequence. Comparison of the structures of PI
      SceI in the absence and presence of substrate reveals major conformational
      changes in both the protein and DNA. Notably, in the protein-splicing domain the
      loop comprising residues 53-70 and adopts a "closed" conformation, thus enabling
      it to interact with the DNA. We have studied the dynamics of DNA binding and
      subsequent loop movement by fluorescence techniques. Six amino acids in loop53-70
      were individually replaced by cysteine and modified by fluorescein. The
      interaction of the modified PI-SceI variants with the substrate, unlabeled or
      labeled with tetramethylrhodamine, was analyzed in equilibrium and stopped-flow
      experiments. A kinetic scheme was established describing the interaction between
      PI-SceI and DNA. It is noteworthy that the apparent hinge-flap motion of loop53
      70 is only observed in the presence of a divalent metal ion cofactor.
      Substitution of the major Mg2+-binding ligands in PI-SceI, Asp-218 and Asp-326,
      by Asn or "nicking" PI-SceI with trypsin at Arg-277, which interferes with
      formation of an active enzyme.substrate complex, both prevent the conformational
      change of loop53-70. Deletion of the loop inactivates the enzyme. We conclude
      that loop53-70 is an important structural element that couples DNA recognition by
      the splicing domain with DNA cleavage by the catalytic domain and as such
      "communicates" with the Mg2+ binding sites at the catalytic centers.

PMID- 14634014
TI  - The structure of echovirus type 12 bound to a two-domain fragment of its cellular
      attachment protein decay-accelerating factor (CD 55).
AB  - Echovirus type 12 (EV12), an Enterovirus of the Picornaviridae family, uses the
      complement regulator decay-accelerating factor (DAF, CD55) as a cellular
      receptor. We have calculated a three-dimensional reconstruction of EV12 bound to
      a fragment of DAF consisting of short consensus repeat domains 3 and 4 from cryo
      negative stain electron microscopy data (EMD code 1057). This shows that, as for
      an earlier reconstruction of the related echovirus type 7 bound to DAF,
      attachment is not within the viral canyon but occurs close to the 2-fold symmetry
      axes. Despite this general similarity our reconstruction reveals a receptor
      interaction that is quite different from that observed for EV7. Fitting of the
      crystallographic co-ordinates for DAF(34) and EV11 into the reconstruction shows
      a close agreement between the crystal structure of the receptor fragment and the
      density for the virus-bound receptor, allowing unambiguous positioning of the
      receptor with respect to the virion (PDB code 1UPN). Our finding that the mode of
      virus-receptor interaction in EV12 is distinct from that seen for EV7 raises
      interesting questions regarding the evolution and biological significance of the
      DAF binding phenotype in these viruses.

PMID- 14634015
TI  - Plasmid P1 RepA is homologous to the F plasmid RepE class of initiators.
AB  - DNA replication of plasmid P1 requires a plasmid-encoded origin DNA-binding
      protein, RepA. RepA is an inactive dimer and is converted by molecular chaperones
      into an active monomer that binds RepA binding sites. Although the sequence of
      RepA is not homologous to that of F plasmid RepE, we found by using fold
      recognition programs that RepA shares structural homology with RepE and built a
      model based on the RepE crystal structure. We constructed mutants in the two
      predicted DNA binding domains to test the model. As expected, the mutants were
      defective in P1 DNA binding. The model predicted that RepA binds the first half
      of the binding site through interactions with the C-terminal DNA binding domain
      and the second half through interactions with the N-terminal domain. The
      experiments supported the prediction. The model was further supported by the
      observation that mutants defective in dimerization map to the predicted subunit
      interface region, based on the crystal structure of pPS10 RepA, a RepE family
      member. These results suggest P1 RepA is structurally homologous to plasmid
      initiators, including those of F, R6K, pSC101, pCU1, pPS10, pFA3, pGSH500, Rts1,
      RepHI1B, RepFIB, and RSF1010.

PMID- 14634016
TI  - DsbB elicits a red-shift of bound ubiquinone during the catalysis of DsbA
      oxidation.
AB  - DsbB is an Escherichia coli plasma membrane protein that reoxidizes the Cys30-Pro
      His-Cys33 active site of DsbA, the primary dithiol oxidant in the periplasm. Here
      we describe a novel activity of DsbB to induce an electronic transition of the
      bound ubiquinone molecule. This transition was characterized by a striking
      emergence of an absorbance peak at 500 nm giving rise to a visible pink color.
      The ubiquinone red-shift was observed stably for the DsbA(C33S)-DsbB complex as
      well as transiently by stopped flow rapid scanning spectroscopy during the
      reaction between wild-type DsbA and DsbB. Mutation and reconstitution experiments
      established that the unpaired Cys at position 44 of DsbB is primarily responsible
      for the chromogenic transition of ubiquinone, and this property correlates with
      the functional arrangement of amino acid residues in the neighborhood of Cys44.
      We propose that the Cys44-induced anomaly in ubiquinone represents its activated
      state, which drives the DsbB-mediated electron transfer.

PMID- 14634017
TI  - Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and
      beta-galactopyranosyl residues in a sequential ordered mechanism.
AB  - Host/parasite interaction mediated by carbohydrate/lectin recognition results in
      the attachment to and invasion of host cells and immunoregulation, enabling
      parasite replication and establishment of infection. Trypanosoma cruzi, the
      protozoan responsible for Chagas disease, expresses on its surface a family of
      enzymatically active and inactive trans-sialidases. The parasite uses the active
      trans-sialidase for glycoprotein sialylation in an unusual trans-glycosylation
      reaction. Inactive trans-sialidase is a sialic acid-binding lectin that
      costimulates host T cells through leucosialin (CD43) engagement. The co-mitogenic
      effect of trans-sialidase can be selectively abrogated by N-acetyllactosamine,
      suggesting the presence of an additional carbohydrate binding domain for
      galactosides, in addition to that for sialic acid. Here we investigated the
      interaction of inactive trans-sialidase in the presence of beta-galactosides. By
      using NMR spectroscopy, we demonstrate that inactive trans-sialidase has a beta
      galactoside recognition site formed following a conformational switch induced by
      sialoside binding. Thus prior positioning of a sialyl residue is required for the
      beta-galactoside interaction. When an appropriate sialic acid-containing molecule
      is available, both sialoside and beta-galactoside are simultaneously accommodated
      in the inactive trans-sialidase binding pocket. This is the first report of a
      lectin recognizing two distinct ligands by a sequential ordered mechanism. This
      uncommon binding behavior may play an important role in several biological
      aspects of T. cruzi/host cell interaction and could shed more light into the
      catalytic mechanism of the sialic acid transfer reaction of enzymatically active
      trans-sialidase.

PMID- 14634018
TI  - Regulation of tyrosinase processing and trafficking by organellar pH and by
      proteasome activity.
AB  - Pigmentation of the hair, skin, and eyes of mammals results from a number of
      melanocyte-specific proteins that are required for the biosynthesis of melanin.
      Those proteins comprise the structural and enzymatic components of melanosomes,
      the membrane-bound organelles in which melanin is synthesized and deposited.
      Tyrosinase (TYR) is absolutely required for melanogenesis, but other melanosomal
      proteins, such as TYRP1, DCT, and gp100, also play important roles in regulating
      mammalian pigmentation. However, pigmentation does not always correlate with the
      expression of TYR mRNA/protein, and thus its function is also regulated at the
      post-translational level. Thus, TYR does not necessarily exist in a catalytically
      active state, and its post-translational activation could be an important control
      point for regulating melanin synthesis. In this study, we used a
      multidisciplinary approach to examine the processing and sorting of TYR through
      the endoplasmic reticulum (ER), Golgi apparatus, coated vesicles, endosomes and
      early melanosomes because those organelles hold the key to understanding the
      trafficking of TYR to melanosomes and thus the regulation of melanogenesis. In
      pigmented cells, TYR is trafficked through those organelles rapidly, but in
      amelanotic cells, TYR is retained within the ER and is eventually degraded by
      proteasomes. We now show that TYR can be released from the ER in the presence of
      protonophore or proton pump inhibitors which increase the pH of intracellular
      organelles, after which TYR is transported correctly to the Golgi, and then to
      melanosomes via the endosomal sorting system. The expression of TYRP1, which
      facilitates TYR processing in the ER, is down-regulated in the amelanotic cells;
      this is analogous to a hypopigmentary disease known as oculocutaneous albinism
      type 3 and further impairs melanin production. The sum of these results shows
      that organellar pH, proteasome activity, and down-regulation of TYRP1 expression
      all contribute to the lack of pigmentation in TYR-positive amelanotic melanoma
      cells.

PMID- 14634019
TI  - 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine) is a newly identified
      advanced glycation end product in cataractous and aged human lenses.
AB  - Post-translational modifications of proteins take place during the aging of human
      lens. The present study describes a newly isolated glycation product of lysine,
      which was found in the human lens. Cataractous and aged human lenses were
      hydrolyzed and fractionated using reverse-phase and ion-exchange high performance
      liquid chromatography (HPLC). One of the nonproteinogenic amino acid components
      of the hydrolysates was identified as a 3-hydroxypyridinium derivative of lysine,
      2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine). The compound was
      synthesized independently from 3-hydroxypyridine and methyl 2-[(tert
      butoxycarbonyl)amino]-6-iodohexanoate. The spectral and chromatographic
      properties of the synthetic OP-lysine and the substance isolated from hydrolyzed
      lenses were identical. HPLC analysis showed that the amounts of OP-lysine were
      higher in water-insoluble compared with water-soluble proteins and was higher in
      a pool of cataractous lenses compared with normal aged lenses, reaching 500
      pmol/mg protein. The model incubations showed that an anaerobic reaction mixture
      of Nalpha-tert-butoxycarbonyllysine, glycolaldehyde, and glyceraldehyde could
      produce the Nalpha-t-butoxycarbonyl derivative of OP-lysine. The irradiation of
      OP-lysine with UVA under anaerobic conditions in the presence of ascorbate led to
      a photochemical bleaching of this compound. Our results argue that OP-lysine is a
      newly identified glycation product of lysine in the lens. It is a marker of aging
      and pathology of the lens, and its formation could be considered as a potential
      cataract risk-factor based on its concentration and its photochemical properties.

PMID- 14634020
TI  - Respiration-dependent removal of exogenous H2O2 in brain mitochondria: inhibition
      by Ca2+.
AB  - In brain mitochondria, state 4 respiration supported by the NAD-linked substrates
      glutamate/malate in the presence of EGTA promotes a high rate of exogenous H2O2
      removal. Omitting EGTA decreases the H2O2 removal rate by almost 80%. The
      decrease depends on the influx of contaminating Ca2+, being prevented by the Ca2+
      uniporter inhibitor ruthenium red. Arsenite is also an inhibitor (maximal effect
      approximately 40%, IC50, 12 microm). The H2O2 removal rate (EGTA present) is
      decreased by 20% during state 3 respiration and by 60-70% in fully uncoupled
      conditions. H2O2 removal in mitochondria is largely dependent on glutathione
      peroxidase and glutathione reductase. Both enzyme activities, as studied in
      disrupted mitochondria, are inhibited by Ca2+. Glutathione reductase is decreased
      by 70% with an IC50 of about 0.9 microm, and glutathione peroxidase is decreased
      by 38% with a similar IC50. The highest Ca2+ effect with glutathione reductase is
      observed in the presence of low concentrations of H2O2. With succinate as
      substrate, the removal is 50% less than with glutamate/malate. This appears to
      depend on succinate-supported production of H2O2 by reverse electron flow at NADH
      dehydrogenase competing with exogenous H2O2 for removal. Succinate-dependent H2O2
      is inhibited by rotenone, decreased DeltaPsi, as described previously, and by
      ruthenium red and glutamate/malate. These agents also increase the measured rate
      of exogenous H2O2 removal with succinate. Succinate-dependent H2O2 generation is
      also inhibited by contaminating Ca2+. Therefore, Ca2+ acts as an inhibitor of
      both H2O2 removal and the succinate-supported H2O2 production. It is concluded
      that mitochondria function as intracellular Ca2+-modulated peroxide sinks.

PMID- 14634021
TI  - The Kindler syndrome protein is regulated by transforming growth factor-beta and
      involved in integrin-mediated adhesion.
AB  - Transforming growth factor-beta1 (TGF-beta1) contributes to tumor invasion and
      cancer progression by increasing the motility of tumor cells. To identify genes
      involved in TGF-beta-mediated cell migration, the transcriptional profiles of
      human mammary epithelial cells (HMEC) treated with TGF-beta were compared with
      untreated cells by cDNA microarray analysis. One gene up-regulated by TGF-beta
      was recently named kindlerin (Jobard, F., Bouadjar, B., Caux, F., Hadj-Rabia, S.,
      Has, C., Matsuda, F., Weissenbach, J., Lathrop, M., Prud'homme, J. F., and
      Fischer, J. (2003) Hum. Mol. Genet. 12, 925-935). This gene is significantly
      overexpressed in some cancers (Weinstein, E. J., Bourner, M., Head, R., Zakeri,
      H., Bauer, C., and Mazzarella, R. (2003) Biochim. Biophys. Acta 1637, 207-216),
      and mutations in this gene lead to Kindler syndrome, an autosomal-recessive
      genodermatosis. TGF-beta stimulation of HMEC resulted in a marked induction of
      kindlerin RNA, and Western blotting demonstrated a corresponding increase in
      protein abundance. Kindlerin displays a putative FERM (four point one ezrin
      radixin moesin) domain that is closely related to the sequences in talin that
      interact with integrin beta subunit cytoplasmic domains. The critical residues in
      the talin FERM domain that mediate integrin binding show a high degree of
      conservation in kindlerin. Furthermore, kindlerin is recruited into a molecular
      complex with the beta1A and beta3 integrin cytoplasmic domains. Consistent with
      these biochemical findings, kindlerin is present at focal adhesions, sites of
      integrin-rich, membrane-substratum adhesion. Additionally, kindlerin is required
      for normal cell spreading. Taken together, these data suggest a role for
      kindlerin in mediating cell processes that depend on integrins.

PMID- 14634022
TI  - Identification of conserved domains in Salmonella muenchen flagellin that are
      essential for its ability to activate TLR5 and to induce an inflammatory response
      in vitro.
AB  - The bacterial surface protein flagellin is widely distributed and well conserved
      among distant bacterial species. We and other investigators have reported
      recently that purified flagellin from Salmonella dublin or recombinant flagellin
      of Salmonella muenchen origin binds to the eukaryotic toll receptor TLR5 and
      activates the nuclear translocation of NF-kappaB and mitogen-activated protein
      kinase, resulting in the release of a host of pro-inflammatory mediators in vitro
      and in vivo. The amino acid sequence alignment of flagellins from various Gram
      negative bacteria shows that the C and N termini are well conserved. It is
      possible that sequences within the N and C termini or both may regulate the pro
      inflammatory activity of flagellin. Here we set out to map more precisely the
      regions in both termini that are required for TLR5 activation and pro
      inflammatory signaling. Systematic deletion of amino acids from either terminus
      progressively reduced eukaryotic pro-inflammatory activation. However, deletion
      of amino acids 95-108 (motif N) in the N terminus and 441-449 (motif C) in the C
      terminus abolished pro-inflammatory activity completely. Site-directed
      mutagenesis analysis provided further evidence for the importance of motifs N and
      C. We also present evidence for the functional role of motifs N and C with the
      TLR5 receptor using a reporter assay system. Taken together, our results
      demonstrate that the pro-inflammatory activity of flagellin results from the
      interaction of motif N with the TLR5 receptor on the cell surface.

PMID- 14634023
TI  - p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial
      translocation.
AB  - p73, an important developmental gene, shares a high sequence homology with p53
      and induces both G(1) cell cycle arrest and apoptosis. However, the molecular
      mechanisms through which p73 induces apoptosis are unclear. We found that p73
      induced apoptosis is mediated by PUMA (p53 up-regulated modulator of apoptosis)
      induction, which, in turn, causes Bax mitochondrial translocation and cytochrome
      c release. Overexpression of p73 isoforms promotes cell death and bax promoter
      transactivation in a time-dependent manner. However, the kinetics of apoptosis do
      not correlate with the increase of Bax protein levels. Instead, p73-induced
      mitochondrial translocation of Bax is kinetically compatible with the induction
      of cell death. p73 is localized in the nucleus and remains nuclear during the
      induction of cell death, indicating that the effect of p73 on Bax translocation
      is indirect. The ability of p73 to directly transactivate PUMA and the direct
      effect of PUMA on Bax conformation and mitochondrial relocalization suggest a
      molecular link between p73 and the mitochondrial apoptotic pathway. Our data
      therefore indicate that PUMA-mediated Bax mitochondrial translocation, rather
      than its direct transactivation, correlates with cell death. Finally, human
      DeltaNp73, an isoform lacking the amino-terminal transactivation domain, inhibits
      TAp73-induced as well as p53-induced apoptosis. The DeltaNp73 isoforms seem
      therefore to act as dominant negatives, repressing the PUMA/Bax system and, thus,
      finely tuning p73-induced apoptosis. Our findings demonstrate that p73 elicits
      apoptosis via the mitochondrial pathway using PUMA and Bax as mediators.

PMID- 14634024
TI  - The meiosis-specific protein kinase Ime2 directs phosphorylation of replication
      protein A.
AB  - In Saccharomyces cerevisiae, the cellular single-stranded DNA-binding protein
      replication protein A (RPA) becomes phosphorylated during meiosis in two discrete
      reactions. The primary reaction is first observed shortly after cells enter the
      meiotic program and leads to phosphorylation of nearly all the detectable RPA.
      The secondary reaction, which requires the ATM/ATR homologue Mec1, is induced
      upon initiation of recombination and only modifies a fraction of the total RPA.
      We now report that correct timing of both RPA phosphorylation reactions requires
      Ime2, a meiosis-specific protein kinase that is critical for proper initiation of
      meiotic progression. Expression of Ime2 in vegetative cells leads to an
      unscheduled RPA phosphorylation reaction that does not require other tested
      meiosis-specific kinases and is distinct from the RPA phosphorylation reaction
      that normally occurs during mitotic growth. In addition, immunoprecipitated Ime2
      catalyzes phosphorylation of purified RPA. Our data strongly suggest that Ime2 is
      an RPA kinase in vivo. We propose that Ime2 directly catalyzes RPA
      phosphorylation in the primary reaction and indirectly promotes the Mec1
      dependent secondary reaction by advancing cells through meiotic progression. Our
      studies have identified a novel meiosis-specific reaction that targets a key
      protein required for DNA replication, repair, and recombination. This pathway
      could be important in differentiating mitotic and meiotic DNA metabolism.

PMID- 14634025
TI  - Molecular characterization of a phospholipase D generating anandamide and its
      congeners.
AB  - Anandamide (N-arachidonoylethanolamine) is known to be an endogenous ligand of
      cannabinoid and vanilloid receptors. Its congeners (collectively referred to as N
      acylethanolamines) also show a variety of biological activities. These compounds
      are principally formed from their corresponding N-acyl-phosphatidylethanolamines
      by a phosphodiesterase of the phospholipase D-type in animal tissues. We purified
      the enzyme from rat heart, and by the use of the sequences of its internal
      peptides cloned its complementary DNAs from mouse, rat, and human. The deduced
      amino acid sequences were composed of 393-396 residues, and showed that the
      enzyme has no homology with the known phospholipase D enzymes but is classified
      as a member of the zinc metallohydrolase family of the beta-lactamase fold. As
      was overexpressed in COS-7 cells, the recombinant enzyme generated anandamide and
      other N-acylethanolamines from their corresponding N-acyl
      phosphatidylethanolamines at comparable rates. In contrast, the enzyme was
      inactive with phosphatidylcholine and phosphatidylethanolamine. Assays of the
      enzyme activity and the messenger RNA and protein levels revealed its wide
      distribution in murine organs with higher contents in the brain, kidney, and
      testis. These results confirm that a specific phospholipase D is responsible for
      the generation of N-acylethanolamines including anandamide, strongly suggesting
      the physiological importance of lipid molecules of this class.

PMID- 14634026
TI  - Oxidative degradation of cardiotoxic anticancer anthracyclines to phthalic acids.
      Novel function or ferrylmyoglobin.
AB  - We show that the pseudoperoxidase activity of ferrylmyoglobin (MbIV) promotes
      oxidative degradation of doxorubicin (DOX), an anticancer anthracycline known to
      induce severe cardiotoxicity. MbIV, formed in vitro by reacting horse heart MbIII
      with H2O2, caused disappearance of the spectrum of DOX at 477 nm and appearance
      of UV-absorbing chromophores that indicated opening and degradation of its
      tetracyclic ring. Electron spray ionization mass spectrometry analyses of
      DOX/MbIV ultrafiltrates showed that DOX degradation resulted in formation of 3
      methoxyphthalic acid, the product of oxidative modifications of its methoxy
      substituted ring D. Other methoxy-substituted anthracyclines similarly released 3
      methoxyphthalic acid after oxidation by MbIV, whereas demethoxy analogs released
      simple phthalic acid. Kinetic and stoichiometric analyses of reactions between
      DOX and MbIII/H2O2 or hemin/H2O2 showed that the porphyrin radical of MbIV
      compound I and the iron-oxo moiety of MbIV-compound II were sequentially involved
      in oxidizing DOX; however, oxidation by compound I formed more 3-methoxyphthalic
      acid than oxidation by compound II. Sizeable amounts of 3-methoxyphthalic acid
      were formed in the heart of mice treated with DOX, in human myocardial biopsies
      exposed to DOX in vitro, and in human cardiac cytosol that oxidized DOX after
      activation of its endogenous myoglobin by H2O2. Importantly, H9c2 cardiomyocytes
      were damaged by low concentrations of DOX but could tolerate concentrations of 3
      methoxyphthalic acid higher than those measured in murine or human myocardium.
      These results unravel a novel function for MbIV in the oxidative degradation of
      anthracyclines to phthalic acids and suggest that this may serve a salvage
      pathway against cardiotoxicity.

PMID- 14634027
TI  - Exercise prevents diabetes-induced impairment in superficial buffer barrier in
      porcine coronary smooth muscle.
AB  - In healthy coronary smooth muscle cells, the superficial sarcoplasmic reticulum
      (SR) buffers rise in intracellular Ca(2+) levels. In diabetic dyslipidemia, basal
      Ca(2+) levels are increased, yet Ca(2+) influx is decreased and SR Ca(2+) uptake
      is increased. Exercise prevents diabetic dyslipidemia-induced increases in basal
      Ca(2+) levels and decreases in Ca(2+) influx. We tested the hypothesis that
      diabetic dyslipidemia impairs Ca(2+) extrusion via a decrease in superficial SR
      and that exercise will prevent these losses. Male Yucatan swine were maintained
      in four treatment groups: control, hyperlipidemic, diabetic dyslipidemic, and
      diabetic dyslipidemic plus aerobically exercise trained. Intracellular Ca(2+)
      levels were measured during depolarization-induced Ca(2+) influx and caffeine
      induced SR Ca(2+) release. Na(+)/Ca(2+) exchanger and plasmalemmal Ca(2+)-ATPase
      activity were assessed by inhibition with low extracellular Na(+) and 5,6
      carboxyeosin, respectively. Superficial SR was quantified using the internal
      membrane dye 3,3'-dihexyloxacarbocyanine iodide (DiOC(6)) and novel analysis
      techniques. We found that, in diabetic dyslipidemia, Ca(2+) extrusion was
      impaired and superficial SR was decreased. Exercise prevented the diabetic
      dyslipidemia-induced decrease in superficial SR and restored plasmalemmal Ca(2+)
      extrusion. On the basis of these results, we conclude exercise attenuates the
      diabetic dyslipidemia-induced impairment in intracellular Ca(2+) regulation.

PMID- 14634028
TI  - Neuromuscular rehabilitation by treadmill running or electrical stimulation after
      peripheral nerve injury and repair.
AB  - Numerous studies have been devoted to the regeneration of the motor pathway
      toward a denervated muscle after nerve injury. However, the regeneration of
      sensory muscle endings after repair by self-anastomosis are little studied. In
      previous electrophysiological studies, our laboratory showed that the functional
      characteristics of tibialis anterior muscle afferents are differentially affected
      after injury and repair of the peroneal nerve with and without chronic
      electrostimulation. The present study focuses on the axonal regeneration of
      mechano- (fibers I and II) and metabosensitive (fibers III and IV) muscle
      afferents by evaluating the recovery of their response to different test agents
      after nerve injury and repair by self-anastomosis during 10 wk of treadmill
      running (LSR). Data were compared with control animals (C), animals with nerve
      lesion and suture (LS), and animals with lesion, suture, and chronic muscle
      rehabilitation by electrostimulation (LSE) with a biphasic current modulated in
      pulse duration and frequency, eliciting a pattern mimicking the activity
      delivered by the nerve to the muscle. Compared with the C group, results
      indicated that 1) muscle weight was smaller in LS and LSR groups, 2) the fatigue
      index was greater in the LS group and smaller in the LSE group, 3)
      metabosensibility remained altered in the LS and LSE groups, and 4)
      mechanosensitivity presented a large increase of the activation pattern in the LS
      and LSE groups. Our data indicated that chronic muscle electrostimulation
      partially favors the recovery of muscle properties (i.e., muscle weight and
      twitch response were close to the C group) and that rehabilitation by treadmill
      running also efficiently induced a better functional muscle afferent recovery
      (i.e., the discharge pattern was similar to the C group). The effectiveness of
      the chronic electromyostimulation and the treadmill exercise on afferent recovery
      is discussed with regard to parameters listed above.

PMID- 14634029
TI  - Evaluation of bioimpedance spectroscopy for measurements of body water
      distribution in healthy women before, during, and after pregnancy.
AB  - Bioimpedance spectroscopy (BIS) is a technique of interest in the study of human
      pregnancy because it can assess extracellular (ECW), intracellular (ICW), and
      total body water (TBW) as ECW plus ICW. The technique requires appropriate
      resistivity coefficients and has not been sufficiently evaluated during the
      reproductive cycle. Therefore, in a methodological study, we estimated ECW, ICW,
      and TBW, by means of BIS, and compared the results with the corresponding
      estimates obtained by using reference methods. Furthermore, results obtained by
      means of population-specific resistivity coefficients were compared with results
      obtained by means of general resistivity coefficients. These comparisons were
      made before pregnancy, in gestational weeks 14 and 32, as well as 2 wk postpartum
      in 21 healthy women. The reference methods were isotope and bromide dilution.
      Average ICW, ECW, and TBW, estimated by means of BIS, were in agreement with
      reference data before pregnancy, in gestational week 14, and postpartum. The
      corresponding comparison in gestational week 32 showed good agreement for ICW,
      whereas estimates by means of BIS were significantly (P < 0.001) lower than the
      corresponding reference values for ECW and TBW. Thus the BIS technique, which was
      based on a model developed for the nonpregnant body, estimated increases in ICW
      accurately, whereas increases in ECW and TBW tended to be underestimated.
      Estimates obtained by using population-specific and general resistivity
      coefficients were very similar. In conclusion, the results indicated that BIS is
      potentially useful for studies during pregnancy but that further work is needed
      before it can be generally applied in such studies.

PMID- 14634030
TI  - Greater effect of diet than exercise training on the fatty acid profile of rat
      skeletal muscle.
AB  - We determined the interaction of diet and exercise-training intensity on membrane
      phospholipid fatty acid (FA) composition in skeletal muscle from 36 female
      Sprague-Dawley rats. Animals were randomly divided into one of two dietary
      conditions: high-carbohydrate (64.0% carbohydrate by energy, n = 18) or high fat
      (78.1% fat by energy, n = 18). Rats in each diet condition were then allocated to
      one of three subgroups: control, which performed no exercise training; low
      intensity (8 m/min) treadmill run training; or high-intensity (28 m/min) run
      training. All exercise-trained rats ran 1,000 m/session, 4 days/wk for 8 wk and
      were killed 48 h after the last training bout. Membrane phospholipids were
      extracted, and FA composition was determined in the red and white vastus
      lateralis muscles. Diet exerted a major influence on phospholipid FA composition,
      with the high-fat diet being associated with a significantly (P < 0.01) elevated
      ratio of n-6/n-3 FA for both red (2.7-3.2 vs. 1.0-1.1) and white vastus lateralis
      muscle (2.5-2.9 vs. 1.2). In contrast, alterations in FA composition as a result
      of either exercise-training protocol were only minor in comparison. We conclude
      that, under the present experimental conditions, a change in the macronutrient
      content of the diet was a more potent modulator of skeletal muscle membrane
      phospholipid FA composition compared with either low- or high-intensity treadmill
      exercise training.

PMID- 14634031
TI  - Intraluminal pressure oscillation enhances subsequent airway contraction in
      isolated bronchial segments.
AB  - A period of deep inspiration in humans has been shown to attenuate subsequent
      bronchoconstriction, a phenomenon termed bronchoprotection. The bronchoprotective
      effect of deep inspiration may be caused though a depression in the force
      production of airway smooth muscle (ASM). We determined the response of whole
      airway segments and isolated ASM to a period of cyclic stretches. Isovolumetric
      contraction to electrical field stimulation (EFS) was assessed in porcine
      bronchial segments before and after intraluminal pressure oscillation from 5 to
      25 cmH(2)O for 10 min at 0.5 Hz. Morphometry showed that this pressure
      oscillation stretched ASM length by 21%. After pressure oscillation, the response
      to EFS was not reduced but instead was modestly enhanced (P < 0.01). Airway
      responses to EFS returned to preoscillation levels 10 min after the end of
      oscillation. The increase in EFS response after pressure oscillation was not
      altered by the addition of indomethacin. In a separate experiment, we assessed
      isometric force in isolated ASM strips before and after length oscillation. The
      amplitude, frequency, and duration of length oscillation were similar to those
      induced in bronchial segments. In contrast to bronchial segments, length
      oscillation of ASM produced a significant depression in isometric force induced
      by EFS (P < 0.01). These results suggest that the response of ASM to length
      oscillation is modified by the airway wall. They also suggest that the phenomenon
      of bronchoprotection reported in some in vivo studies may not be an intrinsic
      property of the airway.

PMID- 14634032
TI  - Cilostazol prevents focal cerebral ischemic injury by enhancing casein kinase 2
      phosphorylation and suppression of phosphatase and tensin homolog deleted from
      chromosome 10 phosphorylation in rats.
AB  - This study shows the in vivo neuroprotective effect of cilostazol against
      cerebral ischemic injury evoked by subjecting rats to 2-h occlusion of middle
      cerebral artery (MCAO) followed by 24-h reperfusion. We observed the signaling
      pathway by which cilostazol suppressed MCAO-induced increased phosphorylation of
      phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and apoptosis
      via increased phosphorylation of casein kinase 2 (CK2). When rats received 30
      mg/kg cilostazol orally two times at 5 min and 4 h after the completion of
      ischemia, the infarct area was significantly reduced in the cortex and striatum
      with improvement of neurological deterioration. Increased DNA fragmentation in
      the penumbral zone was significantly reduced by cilostazol. Cilostazol
      significantly elevated phosphorylation levels of CK2, Akt, and cyclic AMP
      response element-binding protein (CREB) in association with increased Bcl-2 in
      the ischemic area, whereas the elevated PTEN phosphorylation was significantly
      reduced, all of which were antagonized by iberiotoxin, a maxi-K channel blocker,
      administered intracisternally 30 min before ischemia. In conclusion, cilostazol
      ameliorates the neuronal damage by suppression of apoptotic cell death via the
      maxi-K channel opening-coupled up-regulation of CK2 phosphorylation and down
      regulation of PTEN phosphorylation with resultant increase in the Akt and CREB
      phosphorylation and increased Bcl-2 protein.

PMID- 14634033
TI  - Ex situ inhibition of hepatic uptake and efflux significantly changes metabolism:
      hepatic enzyme-transporter interplay.
AB  - The disposition of digoxin and the influence of the organic anion transporting
      polypeptide (Oatp)2 inhibitor rifampicin and the P-glycoprotein (P-gp) inhibitor
      quinidine on its hepatic disposition were examined in the isolated perfused rat
      liver. Livers from groups of rats were perfused in a recirculatory manner after a
      bolus dose of digoxin (10 microg), a dual substrate for Oatp2 and P-gp as well as
      CYP3A. Perfusions of digoxin were also examined in groups of rats in the presence
      of the inhibitors: rifampicin (100 microM) or quinidine (10 microM). In all
      experiments, perfusate samples were collected for 60 min. Digoxin and its primary
      metabolite were determined in perfusate and liver by liquid chromatography/mass
      spectrometry. The area under the curve (AUC) from 0 to 60 min was determined. The
      AUC +/- S.D. of digoxin was increased from control (3880 +/- 210 nM x min) by
      rifampicin (5200 +/- 240 nM x min; p < 0.01) and decreased by quinidine (3220 +/-
      340 nM x min; P < 0.05). It is concluded that rifampicin limits the hepatic
      entrance of digoxin and reduced the hepatic exposure of digoxin to CYP3A by
      inhibiting the basolateral Oatp2 uptake transport, whereas quinidine increased
      the hepatic exposure of digoxin to CYP3A by inhibiting the canalicular P-gp
      transport. These data emphasize the importance of uptake and efflux transporters
      on hepatic drug metabolism.

PMID- 14634034
TI  - Acute cardiovascular effects of sibutramine in conscious rats.
AB  - Sibutramine is a serotonin and norepinephrine reuptake inhibitor, used in the
      treatment of obesity. In this study, cardiovascular effects of sibutramine (0.9,
      3, or 9 mg kg(-1) i.p.) were measured in conscious Sprague-Dawley rats, in the
      absence and presence of beta- and/or alpha-adrenoceptor antagonism (with
      propranolol and/or phentolamine, respectively). Sibutramine caused pressor and
      tachycardic effects, with celiac and mesenteric vasoconstrictions, and hyperemic
      hindquarters vasodilatation. Pretreatment with propranolol inhibited the
      tachycardic and hindquarters vasodilator effect of sibutramine, whereas
      phentolamine inhibited the pressor and vasoconstrictor effects of sibutramine. In
      the presence of phentolamine, sibutramine caused hyperemic mesenteric
      vasodilatation. In preconstricted, isolated, mesenteric vessels, sibutramine and
      its metabolites BTS 54505 (N-desmethylsibutramine) and BTS 54354 (N
      didesmethylsibutramine) (10 microM) produced significant vasodilations. Neither
      sibutramine nor BTS 54505 enhanced vessel sensitivity to norepinephrine, whereas
      BTS 54 354 produced a significant leftward shift in the concentration-response
      curve to norepinephrine. Collectively, the results indicate that the overt
      cardiovascular effects of sibutramine involve alpha-adrenoceptor-mediated celiac
      and mesenteric vasoconstrictions, and beta-adrenoceptor-mediated hindquarters
      vasodilatation and tachycardia. The mesenteric vasodilator response to
      sibutramine, seen in the presence of phentolamine, may be a direct effect of the
      drug and/or its metabolites, on vessel tone. The cardiovascular effects of
      sibutramine in vivo may be secondary to inhibition of peripheral and/or central
      reuptake of monoamines by the metabolites BTS 54354 and/or BTS 54505. It remains
      to explain why BTS 54354, but not BTS 54505, enhanced norepinephrine sensitivity
      in vitro, because both metabolites are potent inhibitors of the norepinephrine
      transporter.

PMID- 14634035
TI  - Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys.
AB  - 3-O-Methylnaltrexone (3-MNTX), a putative antagonist of morphine-6-beta-d
      glucuronide (M6G) receptors, has been reported to block the behavioral effects of
      heroin at doses that do not block those of morphine, suggesting that M6G
      receptors may play a unique role in the addictive properties of heroin. This
      study investigated the effects of 3-MNTX in monkeys trained to discriminate i.v.
      heroin from vehicle or to self-administer i.v. heroin under a progressive-ratio
      schedule. Additional in vitro studies determined the effects of 3-MNTX and
      reference drugs on adenylyl cyclase activity in caudate-putamen membranes of
      monkeys and rats. In drug discrimination experiments, heroin, morphine, and M6G
      substituted for heroin in all subjects, whereas 3-MNTX substituted for heroin in
      one-half the monkeys tested. In these latter monkeys, the effects of 3-MNTX were
      antagonized by naltrexone, and pretreatment with 3-MNTX enhanced the effects of
      heroin, M6G, and morphine, indicative of micro-agonist activity. In monkeys
      showing no substitution of 3-MNTX for heroin, 3-MNTX antagonized the effects of
      heroin, M6G, and morphine. In self-administration experiments, heroin and 3-MNTX
      maintained injections per session significantly above those maintained by vehicle
      when the initial response requirement (IRR) was low; only heroin maintained
      significant self-administration when the IRR was high. In vitro, 3-MNTX inhibited
      adenylyl cyclase activity in both monkey and rat brain membranes. The degree of
      inhibition produced by 3-MNTX was less than that produced by the full agonist [d
      Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO). The results suggest that 3-MNTX
      functions primarily as a partial agonist at micro-receptors in monkeys and do not
      support a singular role for M6G receptors in the abuse-related effects of heroin.

PMID- 14634036
TI  - Functional and pharmacological characterization of the natriuretic peptide
      dependent lipolytic pathway in human fat cells.
AB  - A lipolytic pathway involving natriuretic peptides has recently been discovered
      in human fat cells. Its functional characteristics and the interactions of the
      atrial natriuretic peptide (ANP)-induced effects with adrenergic and insulin
      pathways were studied. Characterization of the action of ANP antagonists, i.e.,
      A71915, anantin, S-28-Y (Ser-28-Tyr, a synthesized peptide), and HS-142-1 (a
      microbial polysaccharide), was performed. Lipolytic assays and intracellular cGMP
      and cAMP determinations were performed on isolated fat cells. Cell membranes were
      used for binding studies. At low concentrations ANP and isoproterenol [beta
      adrenergic receptor (beta-AR) agonist] exerted additive lipolytic effects. The
      alpha(2)-AR pathway did not interfere with that of ANP. Lipolytic effects of ANP
      were unaltered by a 2-h pretreatment of fat cells with insulin, whereas beta-AR
      induced lipolysis was reduced. Homologous desensitization occurred for ANP
      dependent lipolytic pathways. Dendroapsis natriuretic peptide exhibited a similar
      maximal effect but a 10-fold higher lipolytic potency than ANP and mini-ANP (the
      shortest form of ANP). The antagonist A71915 exhibited competitive antagonistic
      properties with a pA(2) value of 7.51. Anantin displayed noncompetitive
      antagonism and exerted an inhibitory action on basal and beta-adrenergic receptor
      induced lipolytic response. S-28-Y exhibited antagonist potencies toward ANP
      induced lipolysis and behaved as a partial lipolytic agonist with a lower pD(2)
      value (7.4 +/- 0.2) than ANP (9.4 +/- 0.3). HS-142-1 exerted the weakest
      antagonistic effects. The results demonstrate that ANP-dependent effects do not
      interfere with beta- and alpha(2)-adrenergic pathways in human fat cells. They
      are unaffected by insulin pretreatments of fat cells but undergo desensitization.
      In the search of potent and specific natriuretic peptide receptor-A antagonist,
      in the human fat cell, A71915 was the only reliable one found.

PMID- 14634037
TI  - Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin
      induced renal cell apoptosis.
AB  - It has been demonstrated recently that rabbit renal proximal tubule cells (RPTC)
      express a novel Ca(2+)-independent phospholipase A(2) (iPLA(2)) whose activity
      localizes to the endoplasmic reticulum (ER-iPLA(2)) and is similar to group VIB
      PLA(2). In this study, the expression of group VIB PLA(2) was examined and the
      role of ER-iPLA(2) in cisplatin-induced apoptosis was determined. Cisplatin
      induced both time- and concentration-dependent RPTC apoptosis as determined by
      p53 nuclear localization, annexin V staining, caspase 3 activity, and chromatin
      condensation. Inhibition of ER-iPLA(2) with bromoenol lactone (5 microM) reduced
      cisplatin-induced annexin V binding 40%, chromatin condensation 55%, and caspase
      3 activity 42%, but had no effect on p53 nuclear localization. Treatment of RPTC
      with the protein kinase C stimulator phorbol 12-myristate 13-acetate increased
      the activity of ER-iPLA(2) 2-fold and increased cisplatin-induced RPTC apoptosis.
      These studies demonstrate that group VIB PLA(2) is expressed in RPTC and suggest
      that RPTC ER-iPLA(2) is the rabbit homolog of group VIB PLA(2). These data also
      demonstrate that ER-iPLA(2) acts downstream of p53 and upstream of caspase 3 to
      mediate cisplatin-induced RPTC apoptosis. Finally, ER-iPLA(2) seems to be
      regulated by protein kinase C.

PMID- 14634038
TI  - Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab
      mertansine (huC242-DM1), and its two components in mice.
AB  - The humanized monoclonal antibody maytansinoid conjugate, cantuzumab mertansine
      (huC242-DM1) that contains on average three to four linked drug molecules per
      antibody molecule was evaluated in CD-1 mice for its pharmacokinetic behavior and
      tissue distribution, and the results were compared with those of the free
      antibody huC242. The pharmacokinetics in blood were similar for (125)I-labeled
      conjugate and antibody with terminal half-lives of 154 and 156 h, respectively.
      Pharmacokinetic analysis using an enzyme-linked immunosorbent assay (ELISA)
      method, which measures intact conjugate in plasma samples revealed a faster
      clearance for the conjugate corresponding to a half-life of 42.2 h. This faster
      clearance is explained as the result of clearance from circulation and
      concomitant clearance of drug from circulating conjugate through linker cleavage.
      An antibody-specific ELISA allowed the determination of the clearance rate of the
      antibody component from circulation. The drug clearance rate from circulating
      conjugate was then calculated as the difference between the clearance of the
      conjugate and the clearance of the antibody component and found to be about three
      times that of the antibody component. The above results were confirmed with a
      conjugate, huC242-[(3)H]DM1, where the linked DM1 drugs carried a stable tritium
      label. Tissue distribution studies with (125)I-labeled conjugate and antibody
      showed antibody-like behavior for the conjugate; the antibody of the conjugate
      did not distribute or bind significantly to any solid tissue.

PMID- 14634039
TI  - Interaction of the novel adenosine uptake inhibitor 3-[1-(6,7-diethoxy-2
      morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)
      quinazolinedione hydrochloride (KF24345) with the es and ei subtypes of
      equilibrative nucleoside transporters.
AB  - Nucleosides such as adenosine, as well as many nucleoside-based drugs, permeate
      cell membranes via a family of equilibrative nucleoside transporters (ENTs). We
      assessed the effects of (3-[1-(6,7-diethoxy-2-morpholino-quinazolin-4
      yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride
      (KF24345), a novel anti-inflammatory agent that potentiates the actions of
      adenosine, on the es (inhibitor-sensitive) and ei (inhibitor-resistant) subtypes
      of ENTs in human, mouse, and rat cells. KF24345 was similar to the prototypical
      high-affinity inhibitor nitrobenzylthioinosine (NBMPR) for blocking the human es
      transporter (K(I) of approximately 0.4 nM), but was 50-fold more effective than
      NBMPR at blocking the human ei transporter (K(I) of approximately 100 nM).
      KF24345 displayed significantly less species heterogeneity in its affinity for
      the es transporter than did dipyridamole, a widely used inhibitor of nucleoside
      transport; KF24345 may thus prove useful as an inhibitor for studies of
      nucleoside metabolism in a range of animal models. Furthermore, KF24345 seemed to
      act as a noncompetitive inhibitor of both [(3)H]NBMPR binding and
      [(3)H]nucleoside uptake by human es transporters, and these kinetics were
      consistent with an observed slow dissociation of KF24345 from the inhibitor
      binding site. KF24345 also exhibited unusual biphasic profiles for inhibition of
      [(3)H]NBMPR binding to membranes prepared from a recombinant human es transporter
      model (PK15-hENT1), suggesting the presence of multiple populations of NBMPR
      binding proteins in these membranes. The atypical tight binding interaction of
      KF24345 with the es transporter may prove useful for the molecular delineation of
      inhibitor binding domains and will facilitate its use as an in vivo inhibitor of
      nucleoside transport in studies focused on the biological effects of adenosine.

PMID- 14634040
TI  - Switching of bradykinin-mediated nociception following partial sciatic nerve
      injury in mice.
AB  - Bradykinin (BK) is well known as a potent mediator of pain and hyperalgesia.
      Using a highly sensitive nociception test, we found that intraplantar (i.pl.)
      injection of BK produced nociceptive hyper-responses in partial sciatic nerve
      injured mice, compared with the control sham-operated animals. By use of
      selective agonists and antagonists, we revealed that BK nociception in sham
      operated mice was mediated through B2 receptor, whereas that in injured mice was
      mediated through B1 receptor. When we examined the activation of extracellular
      signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons upon
      i.pl. injection of BK, phosphorylated ERK was mainly observed in unmyelinated
      neurons in sham-operated mice, and in case of nerve-injured mice, ERK was mainly
      activated in myelinated neurons and satellite cells. The B1 receptor agonist,
      [Lys-des-Arg(9)]-BK also produced nociceptive response and activated ERK only in
      nerve-injured mice. BK or B1 agonist-induced activation of ERK in DRG neurons of
      nerve-injured mice was completely blocked by pretreatment with antisense
      oligodeoxynucleotide (AS-ODN) for B1 receptor. We found that in sham-operated
      mice mainly B2 receptors were expressed in unmyelinated DRG neurons with a very
      little presence of B1 receptor. After nerve injury, B2 receptor expression
      drastically decreased, whereas B1 receptors were newly expressed mainly in
      myelinated DRG neurons and satellite cells. Finally, BK nociception in sham
      operated mice was blocked by AS-ODN for B2 receptors and that in injured mice by
      AS-ODN for B1 receptors. Altogether, these findings confirm a switching of
      receptor and fiber subtype for BK nociception after peripheral nerve injury,
      which might contribute to the pathobiology of neuropathic pain.

PMID- 14634041
TI  - The distribution of the HIV protease inhibitor, ritonavir, to the brain,
      cerebrospinal fluid, and choroid plexuses of the guinea pig.
AB  - Anti-human immunodeficiency virus (HIV) drug penetration into the brain and
      cerebrospinal fluid (CSF) is necessary to tackle HIV within the CNS. This study
      examines movement of [(3)H]ritonavir across the guinea pig blood-brain and blood
      CSF barriers and accumulation within the brain, CSF, and choroid plexus.
      Ritonavir is a protease inhibitor, used in combination therapy (often as a
      pharmacoenhancer) to treat HIV. Drug interactions at brain barrier efflux systems
      may influence the CNS penetration of anti-viral drugs, thus the influence of
      additional protease inhibitors, nucleoside reverse transcriptase inhibitors, and
      non-nucleoside reverse transcriptase inhibitors on [(3)H]ritonavir CNS
      distribution was explored. Additionally, the involvement of transporters on
      [(3)H]ritonavir passage across the brain barriers was assessed. Results from in
      situ brain perfusions and capillary depletion analysis demonstrated that
      [(3)H]ritonavir uptake into the guinea pig brain was considerable (6.6 +/- 0.7
      ml/100 g at 30 min, vascular space corrected), although a proportion of drug
      remained trapped in the cerebral capillaries and did not reach the brain
      parenchyma. CSF uptake was more limited (2.2 +/- 0.4 ml/100 g at 30 min), but
      choroid plexus uptake was abundant (176.7 +/- 46.3 ml/100 g at 30 min).
      [(3)H]Ritonavir brain and CSF uptake was unaffected by neither inhibitors of
      organic anion transport (probenecid and digoxin) or P-glycoprotein
      (progesterone), nor by any additional anti-HIV drugs, indicating that brain
      barrier efflux systems do not significantly limit brain or CSF [(3)H]ritonavir
      accumulation in this model. [(3)H]Ritonavir uptake into the perfused choroid
      plexus was significantly reduced by nevirapine and abacavir, additional perfusion
      studies, and isolated incubated choroid plexus experiments were carried out in an
      attempt to further characterize the transporter involved.

PMID- 14634042
TI  - Developmental expression of human hepatic CYP2C9 and CYP2C19.
AB  - The CYP2C subfamily is responsible for metabolizing many important drugs and
      accounts for about 20% of the cytochrome p450 in adult liver. To determine
      developmental expression patterns, liver microsomal CYP2C9 and -2C19 were
      measured (n = 237; ages, 8 weeks gestation-18 years) by Western blotting and with
      diclofenac or mephenytoin, respectively, as probe substrates. CYP2C9-specific
      content and catalytic activity were consistent with expression at 1 to 2% of
      mature values (i.e., specific content, 18.3 pmol/mg protein and n = 79; specific
      activity, 549.5 pmol/mg/min and n = 72) during the first trimester, with
      progressive increases during the second and third trimesters to levels
      approximately 30% of mature values. From birth to 5 months, CYP2C9 protein values
      varied 35-fold and were significantly higher than those observed during the late
      fetal period, with 51% of samples exhibiting values commensurate with mature
      levels. Less variable CYP2C9 protein and activity values were observed between 5
      months and 18 years. CYP2C19 protein and catalytic activities that were 12 to 15%
      of mature values (i.e., specific content, 14.6 pmol/mg and n = 20; specific
      activity, 18.5 pmol/mg/min and n = 19) were observed as early as 8 weeks of
      gestation and were similar throughout the prenatal period. CYP2C19 expression did
      not change at birth, increased linearly over the first 5 postnatal months, and
      varied 21-fold from 5 months to 10 years. Adult CYP2C19 protein and activity
      values were observed in samples older than 10 years. The ontogeny of CYP2C9 and 
      2C19 were dissimilar among both fetal and 0- to 5-months postnatal samples,
      implying different developmental regulatory mechanisms.

PMID- 14634043
TI  - Ouabain increases sarcoplasmic reticulum calcium release in cardiac myocytes.
AB  - The inotropic and toxic effects of cardiac glycosides are thought to be related
      to their ability to inhibit the Na,K-ATPase. We examined the effects of ouabain
      and its analogs on sarcoplasmic reticulum (SR) Ca(2+) release in intact cat
      ventricular myocytes under Na(+)-free conditions and in myocytes in which the
      sarcolemma was permeabilized using saponin so that cytoplasmic ionic composition
      was fixed by the bath solutions. We also compared ouabain actions in cat myocytes
      to those in rat myocytes because the latter is considered to be a glycoside
      insensitive species. In intact cat myocytes (Na(+)-free conditions), spontaneous
      Ca(2+) sparks were prolonged and frequency, amplitude and width were reduced by
      exposure to ouabain (3 microM). Nearly identical results were obtained with its
      analogs dihydroouabain or ouabagenin (10 microM). The frequency of spontaneous
      Ca(2+) waves was also reduced by ouabain. In contrast, ouabain (100 microM) had
      negligible effects on sparks and waves in rat myocytes in Na(+)-free conditions,
      consistent with the decreased sensitivity to cardiac glycosides observed in this
      species. In cat myocytes permeabilized with saponin (0.01%), ouabain (>or=50 nM)
      decreased spark frequency and increased background SR Ca(2+) leak only when the
      SR was well loaded (free [Ca(2+)] = 275 nM) and not when SR load was low (free
      [Ca(2+)] = 50 nM). Similar effects were observed in rat myocytes only when
      ouabain concentration was 1 microM. These results suggest that the cellular
      actions of cardiac glycosides may include a direct effect on SR Ca(2+) release,
      possibly through activation of SR Ca(2+) release channels (ryanodine receptors).
      In addition, these results are consistent with the idea that direct activation of
      SR Ca(2+) release is dependent on the extent of SR Ca(2+) load, with elevated
      load increasing sensitivity of the channel release mechanism to activation by
      glycoside.

PMID- 14634044
TI  - Catalytic activity and isoform-specific inhibition of rat cytochrome p450 4F
      enzymes.
AB  - Arachidonic acid is omega-hydroxylated to 20-hydroxyeicosatetraenoic acid (20
      HETE), which has effects on vasoactivity and renal tubular transport and has been
      implicated in the regulation of blood pressure. Cytochrome p450 (p450) 4A
      isoforms are generally considered the major arachidonic acid omega-hydroxylases;
      however, little is known about the role of rat CYP4F isoforms in 20-HETE
      formation. The rat CYP4F isoforms, CYP4F1, CYP4F4, CYP4F5, and CYP4F6, were
      heterologously expressed in Escherichia coli, and their substrate specificity in
      fatty acid metabolism was characterized. Substrate-binding assays indicated that
      leukotriene B(4) (LTB(4)) and arachidonic acid bound CYP4F1 and CYP4F4 in a type
      I manner with a K(s) of 25 to 59 microM, and lauric acid bound CYP4F4 poorly.
      Reconstituted CYP4F1 and CYP4F4 catalyzed the omega-hydroxylation of LTB(4) with
      a K(m) of 24 and 31 microM, respectively, and CYP4F5 had minor activity in LTB(4)
      metabolism. Importantly, CYP4F1 and CYP4F4 catalyzed the omega-hydroxylation of
      arachidonic acid with an apparent k(cat) of 9 and 11 min(-1), respectively.
      Lauric acid was a poor substrate for all of the CYP4F isoforms, and CYP4F6 had no
      detectable fatty acid omega-hydroxylase activity. The p450 omega-hydroxylase
      inhibitors 17-octadecynoic acid, 10-undecynyl sulfate, and N-methylsulfonyl-12,12
      dibromododec-11-enamide showed isoform-specific inhibition of CYP4F1- and CYP4F4
      catalyzed omega-hydroxylation of arachidonic acid and potency differences between
      the CYP4A and CYP4F isoforms. These data support a significant role for CYP4F1
      and CYP4F4 in the formation of 20-HETE and identify p450 inhibitors that can be
      used to understand the relative contribution of the CYP4A and CYP4F isoforms to
      renal 20-HETE formation.

PMID- 14634045
TI  - Mitogen-activated protein kinase and caspase signaling pathways are required for
      P2X7 receptor (P2X7R)-induced pore formation in human THP-1 cells.
AB  - Brief activation of the ATP-sensitive P2X(7) receptor (P2X(7)R) stimulates the
      maturation and release of interleukin 1beta (IL-1beta)in macrophages, whereas
      prolonged agonist activation induces the formation of cytolytic pores in cell
      membranes. The present study investigated potential downstream mechanisms
      associated with native human P2X(7)R activation in lipopolysaccharide and
      interferon-gamma differentiated THP-1 cells. 2,3-O-(4-Benzoylbenzoyl)-ATP (BzATP)
      induced pore formation (EC(50) = 35 microM) was blocked by a selective P2X(7)R
      antagonist, 1[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4
      phenylpiperazine (KN-62) (IC(50) = 44 nM) and by pyridoxal phosphate-6-azophenyl
      2-4-disulfonic acid (PPADS) (IC(50) = 344 nM). KN-62 and PPADS also blocked BzATP
      induced IL-1beta release (EC(50) = 617 microM) with IC(50) values of 75 and 3500
      nM, respectively. The selective p38 mitogen-activated protein kinase (MAPK)
      inhibitor, 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole (SB
      202190), potently inhibited BzATP-induced pore formation (IC(50) = 75 nM) but did
      not alter P2X(7)-mediated calcium influx or IL-1beta release. SB 202190 and KN-62
      also attenuated BzATP-mediated activation of phosphorylated p38 MAPK (pp38 MAPK).
      Two caspase inhibitors, YVAD (caspase 1) and DEVD (caspase 3), attenuated both
      BzATP-induced pore formation and IL-1beta release in a concentration-dependent
      fashion. Neither DEVD nor p38-MAPK inhibitors blocked cell membrane pore
      formation evoked by maitotoxin or by activation of human P2X(2a) receptors. These
      results indicate that P2X(7)R-mediated pore formation results from a coordinated
      cascade involving both the p38 MAPK and caspase pathways that is distinct from
      other cytolytic pore-forming mechanisms. In contrast, P2X(7)R-mediated IL-1beta
      release is dependent on caspase activity but not p38 MAPK. Taken together, these
      results support the hypothesis that downstream cellular signaling mechanisms,
      rather than channel dilation, mediate cytolytic pore formation after prolonged
      agonist activation, which underlies P2X(7) receptors.

PMID- 14634046
TI  - Effect of age on in vitro triazolam biotransformation in male human liver
      microsomes.
AB  - We studied age-related changes in enzyme kinetic parameters in human liver
      microsomes (HLMs) in vitro, using triazolam (TRZ), an index of CYP3A activity.
      HLMs were prepared from male livers from four age groups, n = 5 per group: A (14
      20 years), B (21-40 years), C (41-60 years), and D (61-72 years). Mean V(max)
      values in groups B and C for both 1-hydroxytriazolam (1-OH-TRZ) and 4-hydroxy
      triazolam (4-OH-TRZ) formation were significantly greater as compared with groups
      A and D individually, as well as the net intrinsic clearance (sum of the two
      pathways). The mean net intrinsic clearance (Cl(int)) values were 25.2, 89.8, 78,
      and 20.6 nl/min/mg protein in A, B, C, and D, respectively. TRZ Cl(int)
      correlated well with total CYP3A content (r(s) = 0.84; P < 0.0001). Testosterone
      (TST) inhibited 1-OH-TRZ formation and activated 4-OH-TRZ formation in all age
      groups, with no significant differences among the groups; this suggests that the
      drug-drug interaction potential using TRZ and TST as index CYP3A substrates may
      not change with age. Reduced V(max) and Cl(int) for TRZ hydroxylation and CYP3A
      protein in livers from elderly men suggest reduced CYP3A gene expression in this
      group.

PMID- 14634047
TI  - Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid
      insecticide allethrin.
AB  - Pyrethroids are commonly used insecticides for both household and agricultural
      applications. It is generally reported that voltage-gated sodium channels are the
      primary target for toxicity of these chemicals to humans. The phylogenetic and
      structural relatedness between sodium channels and voltage-gated calcium (Ca)
      channels prompted us to examine the effects of the type 1 pyrethroid allethrin on
      the three major classes of mammalian calcium channels exogenously expressed in
      human embryonic kidney 293 cells. We report that all classes of mammalian calcium
      channels are targets for allethrin at concentrations very similar to those
      reported for interaction with sodium channels. Allethrin caused blockade with
      IC(50) values of 7.0 microM for T-type alpha(1G) (Ca(v)3.1), 6.8 microM for L
      type alpha(1C) (Ca(v)1.2), and 6.7 microM for P/Q-type alpha(1A) (Ca(v)2.1)
      channels. Mechanistically, the blockade of calcium channels was found to be
      significantly different than the prolonged opening of mammalian sodium channels
      caused by pyrethroids. In all calcium channel subtypes tested, allethrin caused a
      significant acceleration of the inactivation kinetics and a hyperpolarizing shift
      in the voltage dependence of inactivation. The high-voltage-activated P/Q- and L
      type channels showed a frequency of stimulation-dependent increase in block by
      allethrin, whereas the low-voltage-activated alpha(1G) subtype did not. Allethrin
      did not significantly modify the deactivation kinetics or current-voltage
      relationships of any of the calcium channel types. Our study indicates that
      calcium channels are another primary target for allethrin and suggests that
      blockade of different types of calcium channels may underlie some of the chronic
      effects of low-level pyrethroid poisoning.

PMID- 14634048
TI  - Antithrombotic effects of FK419, a novel nonpeptide platelet GPIIb/IIIa
      antagonist, in a guinea pig photochemically induced middle cerebral artery
      thrombosis model: comparison with ozagrel and argatroban.
AB  - Platelet activation and subsequent aggregation play a key role in the
      pathogenesis of ischemic brain damage. Recent studies revealed that enhanced
      platelet activation is also observed after ischemia, suggesting that secondary
      thrombus formation might participate in the development of cerebral infarction.
      The binding of platelet glycoprotein GPIIb/IIIa (integrin alpha(IIb)beta3) to
      fibrinogen is the final common pathway in platelet aggregation. Therefore,
      GPIIb/IIIa antagonists might be useful in acute ischemic stroke as well as in the
      secondary prevention of ischemic stroke. In the present study, we evaluated the
      effect of three compounds, FK419 ((S)-2-acetylamino-3-[(R)-[1-[3-(piperidin-4-yl)
      propionyl] piperidin-3-ylcarbonyl] amino] propionic acid trihydrate), a novel
      nonpeptide GPIIb/IIIa antagonist, ozagrel, a selective thromboxane A(2) synthase
      inhibitor, and argatroban, a thrombin inhibitor, on middle cerebral artery (MCA)
      patency and ischemic brain damage using photochemically induced MCA thrombosis
      model in guinea pigs. FK419, ozagrel, or argatroban was administered 5 min after
      the termination of photoirradiation. FK419 dose-dependently improved MCA patency
      by decreasing the total occlusion time, time to continuous reperfusion, and the
      number of cyclic flow reductions, at doses that inhibited ADP-induced platelet
      aggregation ex vivo. In contrast, ozagrel only improved total occlusion time, and
      argatroban showed no improvement in MCA patency. FK419 also reduced ischemic
      brain damage in a dose-dependent fashion, whereas ozagrel and argatroban did not.
      Finally, FK419 ameliorated neurological deficits, whereas ozagrel and argatroban
      did not. These results indicate that FK419, a GPIIb/IIIa antagonist, ameliorates
      ischemic brain damage by improving MCA patency after occlusion and that FK419 is
      a promising candidate for the treatment of acute ischemic stroke.

PMID- 14634049
TI  - Comparison of three different A1 adenosine receptor antagonists on infarct size
      and multiple cycle ischemic preconditioning in anesthetized dogs.
AB  - A(1) adenosine receptor (AR) antagonists are effective diuretic agents that may
      be useful for treating fluid retention disorders including congestive heart
      failure. However, antagonism of A(1)ARs is potentially a concern when using these
      agents in patients with ischemic heart disease. To address this concern, the
      present study was designed to compare the actions of the A(1)AR antagonists CPX
      (1,3-dipropyl-8-cyclopentylxanthine), BG 9719 (1,3-dipropyl-8-[2-(5,6
      epoxynorbornyl)]xanthine), and BG 9928 (1,3-dipropyl-8-[1-(4-propionate)-bicyclo
      [2,2,2]octyl]xanthine) on acute myocardial ischemia/reperfusion injury and
      ischemic preconditioning (IPC) in an in vivo dog model of infarction. Barbital
      anesthetized dogs were subjected to 60 min of left anterior descending coronary
      artery occlusion followed by 3 h of reperfusion, after which infarct size was
      assessed by staining with triphenyltetrazolium chloride. IPC was elicited by four
      5-min occlusion/5-min reperfusion cycles produced 10 min before the 60-min
      occlusion. Multiple-cycle IPC produced a robust reduction ( approximately 65%) in
      infarct size; this effect of IPC on infarct size was not abrogated in dogs
      pretreated with any of the three AR antagonists. Surprisingly, in the absence of
      IPC, pretreatment with CPX or BG 9928 before occlusion or immediately before
      reperfusion resulted in significant reductions ( approximately 40-50%) in
      myocardial infarct size. However, treatment with an equivalent dose of BG 9719
      had no similar effect. We conclude that the A(1)AR antagonists BG 9719, BG 9928,
      and CPX do not exacerbate cardiac injury and do not interfere with IPC induced by
      multiple ischemia/reperfusion cycles. We discuss the possibility that the
      cardioprotective actions of CPX and BG 9928 may be related to antagonism of
      A(2B)ARs.

PMID- 14634050
TI  - D2 dopamine receptors modulate Galpha-subunit coupling of the CB1 cannabinoid
      receptor.
AB  - CB(1) cannabinoid (CB(1)) and D(2) dopamine (D(2)) receptors are known to couple
      to the G protein Galpha(i/o). It has been reported that concurrent activation of
      D(2) receptors and CB(1) receptors, in primary striatal neuronal culture,
      promotes functional CB(1) receptor coupling to Galpha(s) resulting in elevations
      in intracellular cyclic AMP levels. We now report that in the absence of D(2)
      receptors, acute activation of CB(1) receptors inhibits cyclic AMP accumulation,
      whereas the presence of D(2) receptors promotes CB(1)-stimulated cAMP
      accumulation, presumably through Galpha(s). This Galpha(s) subunit switching was
      not prevented by pertussis toxin treatment and occurred in the presence and
      absence of D(2) receptor activation. Thus, coexpression of the D(2) receptor with
      the CB(1) receptor was sufficient to switch the coupling of the CB(1) receptors
      from Galpha(i/o) to Galpha(s). Persistent activation of D(2) receptors resulted
      in heterologous sensitization of adenylate cyclase to subsequent stimulation by
      forskolin, whereas the persistent activation of CB(1) receptors did not.
      Additional studies in human embryonic kidney cells cotransfected with D(2) and
      CB(1) receptors revealed that persistent activation (18 h) of D(2) receptors
      induced a switch of CB(1) receptor coupling from Galpha(s) to Galpha(i/o). This
      D(2) receptor-induced effect allowed for CB(1) receptor-mediated inhibition of
      cyclic AMP accumulation. The present studies suggest D(2) receptors may have a
      significant modulatory role in determining the G protein coupling specificity of
      CB(1) receptors.

PMID- 14634051
TI  - Differential effects of coconut oil- and fish oil-enriched diets on
      tricarboxylate carrier in rat liver mitochondria.
AB  - The mitochondrial tricarboxylate carrier (TCC) plays an important role in
      lipogenesis being TCC-responsible for the efflux from the mitochondria to the
      cytosol of acetyl-CoA, the primer for fatty acid synthesis. In this study, we
      investigated the effects of two high-fat diets with different fatty acid
      composition on the hepatic TCC activity. Rats were fed for 3 weeks on a basal
      diet supplemented with 15% of either coconut oil (CO), abundant in medium-chain
      saturated fatty acids, or fish oil (FO), rich in n-3 polyunsaturated fatty acids.
      Mitochondrial fatty acid composition was differently influenced by the dietary
      treatments, while no appreciable change in phospholipid composition and
      cholesterol level was observed. Compared with CO, the TCC activity was markedly
      decreased in liver mitochondria from FO-fed rats; kinetic analysis of the carrier
      revealed a decrease of the Vmax, with no change of the Km. No difference in the
      Arrhenius plot between the two groups was observed. Interestingly, the carrier
      protein level and the corresponding mRNA abundance decreased following FO
      treatment. These data indicate that FO administration markedly decreased the TCC
      activity as compared with CO. This effect is most likely due to a reduced gene
      expression of the carrier protein.

PMID- 14634053
TI  - Series introduction: molecular and cellular basis of septic shock.
AB  - This series of overviews was contributed by participants of a Keystone Symposium,
      which was convened in early 2003 to address the topic of septic shock in an
      interdisciplinary manner. This occasion reflects a resurgence of interest in
      septic shock as a disease that may soon be approachable by new therapeutic
      interventions.

PMID- 14634054
TI  - Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of
      CXC chemokine receptor 6-expressing cells.
AB  - Direct contacts between dendritic cells (DCs) and T cells or natural killer T
      (NKT) cells play important roles in primary and secondary immune responses. SR
      PSOX/CXC chemokine ligand 16 (CXCL16), which is selectively expressed on DCs and
      macrophages, is a scavenger receptor for oxidized low-density lipoprotein and
      also the chemokine ligand for a G protein-coupled receptor CXC chemokine receptor
      6 (CXCR6), expressed on activated T cells and NKT cells. SR-PSOX/CXCL16 is the
      second transmembrane-type chemokine with a chemokine domain fused to a mucin-like
      stalk, a structure very similar to that of fractalkine (FNK). Here, we
      demonstrate that SR-PSOX/CXCL16 functions as a cell adhesion molecule for cells
      expressing CXCR6 in the same manner that FNK functions as a cell adhesion
      molecule for cells expressing CX(3)C chemokine receptor 1 (CX(3)CR1) without
      requiring CX(3)CR1-mediated signal transduction or integrin activation. The
      chemokine domain of SR-PSOX/CXCL16 mediated the adhesion of CXCR6-expressing
      cells, which was not impaired by treatment with pertussis toxin, a Galphai
      protein blocker, which inhibited chemotaxis of CXCR6-expressing cells induced by
      SR-PSOX/CXCL16. Furthermore, the adhesion activity was up-regulated by treatment
      of SR-PSOX/CXCL16-expressing cells with a metalloprotease inhibitor, which
      increased surface expression levels of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 is a
      unique molecule that not only attracts T cells and NKT cells toward DCs but also
      supports their firm adhesion to DCs.

PMID- 14634055
TI  - Reduction in shear stress, activation of the endothelium, and leukocyte priming
      are all required for leukocyte passage across the blood--retina barrier.
AB  - The passage of leukocytes across the blood-retina barrier at the early stages of
      an inflammatory reaction is influenced by a complex series of interactions about
      which little is known. In particular, the relationship between hydrodynamic
      factors, such as shear stress and leukocyte velocity, to the adherence and
      subsequent extravasation of leukocytes into the retina is unclear. We have used a
      physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes
      circulating in the retina, followed by confocal microscopy of retinal flatmounts
      to detect infiltrating cells at the early stage of experimental autoimmune
      uveitis. This has shown that retinal vessels are subjected to high shear stress
      under normal circumstances. During the inflammatory reaction, shear stress in
      retinal veins is reduced 24 h before leukocyte infiltration. This reduction is
      negatively correlated with leukocyte rolling and sticking in veins and
      postcapillary venules, the sites of leukocyte extravasation. Activation of
      vascular endothelial cells is also a prerequisite for leukocyte rolling and
      infiltration. In addition, antigen priming of leukocytes is influential at the
      early stage of inflammation, and this is seen clearly in the reduction in rolling
      velocity and adherence of the primed leukocytes in activated retinal venules, 9
      days postimmunization.

PMID- 14634056
TI  - Gene expression in mature neutrophils: early responses to inflammatory stimuli.
AB  - Neutrophils provide an essential defense against bacterial and fungal infection
      and play a major role in tissue damage during inflammation. Using oligonucleotide
      microarrays, we have examined the time course of changes in gene expression
      induced by stimulation with live, opsonized Escherichia coli, soluble
      lipopolysaccharide, and the chemoattractant formyl-methionyl-leucyl
      phenylalanine. The results indicate that activated neutrophils generate a broad
      and vigorous set of alterations in gene expression. The responses included
      changes in the levels of transcripts encoding 148 transcription factors and
      chromatin-remodeling genes and 95 regulators of protein synthesis or stability.
      Clustering analysis showed distinct temporal patterns with many rapid changes in
      gene expression within the first hour of exposure. In addition to the temporal
      clustering of genes, we also observed rather different profiles associated with
      each stimulus, suggesting that even a nonvirulent organism such as E. coli is
      able to play a dynamic role in shaping the inflammatory response. Principal
      component analysis of transcription factor genes demonstrated clear separation of
      the neutrophil-response clusters from those of resting and stimulated human
      monocytes. The present study indicates that combinatorial transcriptional
      regulation including alterations of chromatin structure may play a role in the
      rapid changes in gene expression that occur in these terminally differentiated
      cells.

PMID- 14634057
TI  - The spreading of B lymphocytes induced by CD44 cross-linking requires actin,
      tubulin, and vimentin rearrangements.
AB  - CD44 is a polymorphic family of adhesion molecules widely distributed on cells
      and tissues. CD44 is up-regulated on activated lymphocytes, and it can function
      as a receptor, mediating rolling and migration. Although it has been demonstrated
      that anti-CD44 antibodies bound to tissue-culture plates induce multidirectional
      emission of retractile dendrites ("spreading") in activated murine B lymphocytes,
      the involvement of cytoskeleton elements in this phenomenon is largely unknown.
      In this work, it is shown that the generation of dendrites induced by CD44 cross
      linking in activated B cells depends on actin, microtubules, and vimentin
      reorganization. Immunofluorescence analysis showed that dendrite formation began
      with actin polymerization, and its extension was favored by microtubules and
      intermediate filaments of vimentin oriented to the polymerized actin.
      Pretreatment of activated B lymphocytes with cytochalasin E inhibited the
      dendrites formation; moreover, when cells were treated with this drug at
      different time points during the dendrite formation process, the stability of the
      dendrites was affected. In contrast, although the treatment with colchicine and
      nocodazole (tubulin polymerization inhibitors) inhibited the dendrites formation,
      it did not inhibit the initial phase of actin polymerization. According to these
      results, B cell spreading and dendrite formation induced by anti-CD44 antibodies
      require coordinated rearrangements of actin, microtubules, and vimentin, being
      the actin cytoskeleton, the most important element that confers stability and
      drives the morphological changes during B cell spreading, conceivably preparing B
      lymphocytes for locomotion.

PMID- 14634058
TI  - Expression of CD30 and Ox40 on T lymphocyte subsets is controlled by distinct
      regulatory mechanisms.
AB  - Members of the TNF receptor (TNFR) superfamily are cell-surface proteins that can
      be found on most cell types including lymphocytes. Although some TNFR-related
      molecules are constitutively expressed, others, such as CD30 and Ox40, are
      induced upon activation of lymphocytes. CD30 and Ox40 are predominantly expressed
      on activated T helper (T(h))2 cells. Both receptors can activate c-Jun N-terminal
      kinase (JNK) and nuclear factor-kappaB (NF-kappaB) and have been suggested to
      play costimulatory roles in lymphocyte activation. To gain further insight into
      events triggered by both TNFR-related molecules, a detailed analysis of their
      expression patterns has been performed. We found that CD30 and Ox40 were
      coexpressed on T(h)2 cells. However, in contrast to CD30, Ox40 was also expressed
      on T(h)1 cells. Although expression of both receptors is augmented by interleukin
      4, only CD30 expression is dependent on signal transducer and activator of
      transcription (STAT)-6-mediated signaling. Differences in the regulatory pathways
      controlling expression of CD30 and Ox40 suggest distinct, functional effects
      triggered by the two TNFR-related molecules during lymphocyte activation.

PMID- 14634059
TI  - Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine
      production and mitogen-activated protein kinase expression.
AB  - Age-related changes in immunity render elderly individuals more susceptible to
      infections than the young. Previous work by our laboratory and others showed that
      macrophages from aged mice are functionally impaired. Macrophages produce
      proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and
      interleukin (IL)-6, when stimulated with lipopolysaccharide (LPS), which signals
      through Toll-like receptor-4 (TLR4) and requires activation of mitogen-activated
      protein kinases (MAPKs). We investigated whether aging is associated with
      alterations in TNF-alpha and IL-6 production and MAPK expression and activation
      in thioglycollate-elicited peritoneal macrophages from mice. Kinetics and LPS
      dose-responsiveness of macrophage TNF-alpha production did not differ by age.
      Unstimulated macrophages did not differ by age in their cytokine production.
      However, LPS-stimulated (100 ng/mL) cultures from aged mice produced 100 +/- 30
      pg/mL TNF-alpha and 6000 +/- 2000 pg/mL IL-6, and those from young mice produced
      280 +/- 50 pg/mL and 10,650 +/- 10 pg/mL, respectively (P<0.05). Likewise, levels
      of activated MAPKs did not differ by age in unstimulated macrophages, and LPS
      stimulated macrophages from aged mice had <70% activated p38 and c-jun NH(2)
      terminal kinase (JNK) than those of young controls. Of particular interest, we
      observed >25% reduction of total p38 and JNK in macrophages from aged mice
      relative to young. In addition, surface TLR4 levels did not vary with age. We
      conclude that macrophages from aged mice exhibited suppressed proinflammatory
      cytokine production, which correlated with diminished total levels and LPS
      stimulated activation of p38 and JNK. These observations suggest that decreased
      MAPK expression could be a mechanism responsible for age-related deterioration of
      the immune system.

PMID- 14634060
TI  - Alpha-defensin expression during myelopoiesis: identification of cis and trans
      elements that regulate expression of NP-3 in rat promyelocytes.
AB  - Alpha-defensins are antimicrobial peptides that contribute to innate-immune
      functions of neutrophils and intestinal Paneth cells. Transcription of alpha
      defensin genes occurs early in neutrophilic myelopoeisis. To examine the
      mechanisms that regulate alpha-defensin gene expression, we analyzed
      transcription of rat neutrophil alpha-defensin NP-3 in D4 cells, a subclone of
      the promyelocytic cell line IPC-81. Northern blot analysis showed that D4 cells
      express fivefold higher levels of alpha-defensin mRNA than the parental cell line
      in a manner relatively independent of passage number. Increased levels of steady
      state mRNA in D4 cells correlated with markedly elevated peptide levels detected
      by immunocytochemical staining. To identify the cis-acting DNA elements involved
      in tissue-specific expression, D4 cells were transfected with luciferase reporter
      constructs containing NP-3 gene 5'-flanking sequences. Analyses of transfected D4
      cells demonstrated that the proximal 87 base pair (bp) sequence contained cis
      acting DNA elements necessary for optimal promoter activity. Mutational analyses
      within the 87-bp region suggested the involvement of the CAAT box and a putative
      polyoma enhancer-binding protein 2/core-binding factor (PEBP2/CBF) site in
      defensin gene transcription. Transient transfection analyses using tandem repeats
      of oligonucleotides containing these sequences demonstrated that proximity of the
      CAAT box and PEBP2/CBF site was important for defensin promoter activity.
      Electrophoretic mobility shift assays indicated that PEBP2/CBF or a PEBP2/CBF
      related protein was involved in a specific protein-DNA interaction occurring
      within a DNA fragment containing the CAAT and PEBP2/CBF sequences. These data
      identify functional trans- and cis-elements that regulate rat defensin gene
      expression in high defensin-expressing promyelocytic cells.

PMID- 14634061
TI  - Acute ethanol exposure inhibits macrophage IL-6 production: role of p38 and
      ERK1/2 MAPK.
AB  - Acute ethanol consumption has been linked to an increase in infectious
      complications in trauma and burn patients. Ethanol modifies production of a
      variety of macrophage-derived immunoregulatory mediators. Lipopolysaccharide
      (LPS), a potent stimulator of inflammatory responses in macrophages, activates
      several intracellular signaling pathways, including mitogen-activated protein
      kinases (MAPK). In the current study, we investigated the effect of acute ethanol
      exposure on in vivo activation of p38 and extracellularly regulated kinases 1 and
      2 (ERK1/2) MAPK in murine macrophages and the corresponding, LPS-stimulated
      interleukin (IL)-6 production. We demonstrated that a single dose of ethanol
      transiently down-regulated p38 and ERK1/2 activation levels (3-24 h after
      treatment) and impaired IL-6 synthesis. Ethanol-related reduction in IL-6
      production was not further affected by the presence of inhibitors of p38 and
      ERK1/2 (SB 202190 and PD 98059, respectively). These results demonstrate that
      acute ethanol exposure can impair macrophage IL-6 production and indicate that
      this effect may result from ethanol-induced alterations in intracellular
      signaling through p38 and ERK1/2.

PMID- 14634062
TI  - Rapid and extensive membrane reorganization by dendritic cells following exposure
      to bacteria revealed by high-resolution imaging.
AB  - Using live cell imaging, we demonstrate that immature dendritic cells (DC)
      derived from human peripheral blood monocytes undergo pronounced morphologic
      changes in vitro within minutes of exposure to unopsonized Escherichia coli,
      developing extensive membrane veils that efficiently capture additional bacteria.
      Internalization does not occur in the veils, but instead, bacteria are
      transported to the central region of the cell, where they sink directly into the
      plasma membrane. In contrast, exposure to polystyrene beads does not induce
      notable changes in cell morphology, and DC do not efficiently capture beads when
      introduced alone or mixed with bacteria. Long dendritic processes were also
      visualized in some cells that allowed capture of clumps of bacteria at a distance
      of more than 100 microm. These results demonstrate that immature DC can
      distinguish between inert particles and bacteria and alter their shape and
      phagocytic capacity in response to the latter.

PMID- 14634063
TI  - Gene-expression profiling of CD34+ cells from various hematopoietic stem-cell
      sources reveals functional differences in stem-cell activity.
AB  - The replacement of bone marrow (BM) as a conventional source of stem cell (SC) by
      umbilical cord blood (UCB) and granulocyte-colony stimulating factor-mobilized
      peripheral blood SC (PBSC) has brought about clinical advantages. However,
      several studies have demonstrated that UCB CD34(+) cells and PBSC significantly
      differ from BM CD34(+) cells qualitatively and quantitatively. Here, we
      quantified the number of SC in purified BM, UCB CD34(+) cells, and CD34(+) PBSC
      using in vitro and in vivo assays for human hematopoietic SC (HSC) activity. A
      cobblestone area-forming cell (CAFC) assay showed that UCB CD34(+) cells
      contained the highest frequency of CAFC(wk6) (3.6- to tenfold higher than BM
      CD34(+) cells and PBSC, respectively), and the engraftment capacity in vivo by
      nonobese diabetic/severe combined immunodeficiency repopulation assay was also
      significantly greater than BM CD34(+), with a higher proportion of CD45(+) cells
      detected in the recipients at a lower cell dose. To understand the molecular
      characteristics underlying these functional differences, we performed several DNA
      microarray experiments using Affymetrix gene chips, containing 12,600 genes.
      Comparative analysis of gene-expression profiles showed differential expression
      of 51 genes between BM and UCB CD34(+) SC and 64 genes between BM CD34(+) cells
      and PBSC. These genes are involved in proliferation, differentiation, apoptosis,
      and engraftment capacity of SC. Thus, the molecular expression profiles reported
      here confirmed functional differences observed among the SC sources. Moreover,
      this report provides new insights to describe the molecular phenotype of CD34(+)
      HSC and leads to a better understanding of the discrepancy among the SC sources.

PMID- 14634064
TI  - Desialylation of glycoconjugates on the surface of monocytes activates the
      extracellular signal-related kinases ERK 1/2 and results in enhanced production
      of specific cytokines.
AB  - Modulation of the sialic acid content of cell-surface glycoproteins and
      glycolipids influences the functional capacity of cells of the immune system. The
      role of sialidase(s) and the consequent desialylation of cell surface
      glycoconjugates in the activation of monocytes have not been established. In this
      study, we show that desialylation of glycoconjugates on the surface of purified
      monocytes using exogenous neuraminidase (NANase) activated extracellular signal
      regulated kinase 1/2 (ERK 1/2), an intermediate in intracellular signaling
      pathways. Elevated levels of phosphorylated ERK 1/2 were detected in desialylated
      monocytes after 2 h of NANase treatment, and increased amounts persisted for at
      least 2 additional hours. Desialylation of cell surface glycoconjugates also led
      to increased production of interleukin (IL)-6, macrophage inflammatory protein
      (MIP)-1alpha, and MIP-1beta by NANase-treated monocytes that were maintained in
      culture. Neither increased levels of phosphorylated ERK 1/2 nor enhanced
      production of cytokines were detected when NANase was heat-inactivated before
      use, demonstrating the specificity of NANase action. Treatment of monocytes with
      gram-negative bacterial lipopolysaccharide (LPS) also led to enhanced production
      of IL-6, MIP-1alpha, and MIP-1beta. The amount of each of these cytokines that
      was produced was markedly increased when monocytes were desialylated with NANase
      before exposure to LPS. These results suggest that changes in the sialic acid
      content of surface glycoconjugates influence the activation of monocytes.

PMID- 14634065
TI  - Comparative cytokine profile of human skin mast cells from two compartments-
      strong resemblance with monocytes at baseline but induction of IL-5 by IL-4
      priming.
AB  - Although known as heterogenous, mast cells (MC) are believed to induce allergic
      inflammation, partially by secretion of T helper cell type 2 (Th2) cytokines. We
      show here that MC purified from two human skin compartments produce cytokines
      that are primarily associated with inflammation and innate immunity [interleukin
      (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha)]. Although these
      are detectable even without stimulation, immunoglobulin (Ig)E receptor cross
      linking is able to enhance only TNF-alpha production, but phorbol 12-myristate 13
      acetate additionally promotes IL-1beta and IL-8. With the exception of TNF-alpha,
      the presence of serum has a positive impact on cytokine production. Although IL
      13 transcripts (but not those for IL-4 and -5) are produced by skin MC, all Th2
      cytokines remain undetectable in the supernatants or lysates of MC from foreskin
      and breast skin by all treatments. Therefore, rather than sharing similarity with
      Th2 cells, the cytokine profile of skin MC at baseline resembles that of
      monocytes. Of note, MC precultured in the presence of IL-4 [alone or plus stem
      cell factor (SCF)] before anti-IgE stimulation, acquired the ability to produce
      IL-5, and IL-1beta was concomitantly suppressed. Additionally, strong up
      regulation of IL-6 by SCF was observed, which was inhibited by IL-4. In summary,
      we present a detailed analysis of the cytokine array of human skin MC immediately
      upon isolation; demonstrate that MC from different skin compartments, although
      producing the same pattern of cytokines, display quantitative differences in
      several aspects; and provide further evidence that MC possess a proinflammatory
      capacity, which can, however, be altered by microenvironmental stimuli,
      substantiating the marked plasticity of the cells.

PMID- 14634066
TI  - Immunomodulatory effect of decoy receptor 3 on the differentiation and function
      of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory
      mechanism to clinical implication.
AB  - To investigate the regulatory effects of decoy receptor 3 (DcR3) on the
      differentiation and function of dendritic cells (DCs), bone marrow-derived DCs
      (BM-DCs) from nonobese diabetic (NOD) mice were cultured with recombinant DcR3.Fc
      protein. Their differentiating phenotypes and T cell-stimulating functions were
      then evaluated. Expression of CD11c, CD40, CD54, and major histocompatibility
      complex I-A(g7) was reduced in cells cultured with additional DcR3.Fc, compared
      with DCs incubated with granulocyte macrophage-colony stimulating factor and
      interleukin (IL)-4, indicating that DcR3 interferes with the differentiation and
      maturation of BM-DCs. One of the most striking effects of DcR3.Fc on the
      differentiation of DCs was the up-regulation of CD86 and down-regulation of CD80,
      suggesting a modulatory potential to skew the T cell response toward the T helper
      cell type 2 (Th2) phenotype. Consistent with this, the proliferation of CD4(+) T
      cells cocultured with DcR3.Fc-treated DCs was significantly reduced compared with
      that of T cells stimulated by normal DCs. Moreover, the secretion of interferon
      gamma from T cells cocultured with DcR3.Fc-treated DCs was profoundly suppressed,
      indicating that DcR3 exerts a Th1-suppressing effect on differentiating DCs.
      Furthermore, adoptive transfer experiments revealed that NOD/severe combined
      immunodeficiency mice received DcR3.Fc-treated DCs, and subsequently,
      autoreactive T cells showed delayed onset of diabetes and a decrease in diabetic
      severity compared with mice that received normal DCs and T cells, suggesting a
      future therapeutic potential in autoimmune diabetes. Data from two-dimensional
      gel electrophoresis and matrix-assisted laser desorption/ionization-time-of
      flight analysis show an up-regulation of some proteins-such as mitogen-activated
      protein kinase p38 beta, cyclin-dependent kinase 6, and signal-induced
      proliferation-associated gene 1-and a down-regulation of the IL-17 precursor;
      tumor necrosis factor-related apoptosis-inducing ligand family member-associated
      nuclear factor-kappaB activator-binding kinase 1; and Golgi S-nitroso-N
      acetylpenicillamine in cells treated with DcR3, further demonstrating its effect
      on DC differentiation and function.

PMID- 14634067
TI  - RhoA activation promotes transendothelial migration of monocytes via ROCK.
AB  - Monocyte infiltration into inflamed tissue requires the initial arrest of the
      cells on the endothelium followed by firm adhesion and their subsequent
      migration. Migration of monocytes and other leukocytes is believed to involve a
      coordinated remodeling of the actin cytoskeleton. The small GTPases RhoA, Rac1,
      and Cdc42 are critical regulators of actin reorganization. In this study, we have
      investigated the role of Rho-like GTPases RhoA, Rac1, and Cdc42 in the adhesion
      and migration of monocytes across brain endothelial cells by expressing their
      constitutively active or dominant-negative constructs in NR8383 rat monocytic
      cells. Monocytes expressing the active form of Cdc42 show a reduced migration,
      whereas Rac1 expression did not affect adhesion or migration. In contrast,
      expression of the active form of RhoA in monocytes leads to a dramatic increase
      in their adhesion and migration across endothelial cells. The effect of RhoA was
      found to be mediated by its down-stream effector Rho kinase (ROCK), as
      pretreatment with the selective ROCK inhibitor Y-27632 prevented this enhanced
      adhesion and migration. These results demonstrate that RhoA activation in
      monocytes is sufficient to enhance adhesion and migration across monolayers of
      endothelial cells.

PMID- 14634068
TI  - Chemotactic activity of S100A8 and S100A9.

PMID- 14634069
TI  - Early T lineage progenitors: new insights, but old questions remain.

PMID- 14634070
TI  - Cutting edge: SDS-stable Fas microaggregates: an early event of Fas activation
      occurring with agonistic anti-Fas antibody but not with Fas ligand.
AB  - The 45 kDa Fas or CD95 receptor triggers apoptosis via the caspase cascade when
      stimulated by its ligand FasL or by agonistic Abs. Activated Fas receptors seem
      to oligomerize very early into SDS-stable and reducing agent-resistant
      microaggregates of 200-250 kDa on SDS-PAGE. However, these microaggregates have
      so far only been reported using agonistic anti-Fas Abs, and no results have been
      reported using FasL. Here, we demonstrate that the microaggregates do not form in
      response to FasL, while they always appear in response to the agonistic Ab, in
      four different cell lines and in normal lymphocytes from human blood. Therefore,
      the Fas microaggregates are not required for the induction of apoptosis via FasL.
      These results also suggest that subtle differences exist in the apoptotic
      pathways triggered by anti-Fas agonistic Abs and by FasL.

PMID- 14634071
TI  - Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected
      Vietnamese intravascular drug users.
AB  - We addressed the role of innate immunity in the protection against HIV-1
      infection by studying NK cell function in 37 Vietnamese intravascular drug users
      (IDUs), who appeared to remain HIV-1 uninfected despite many years of high-risk
      exposure (exposed uninfected, EU), 10 IDUs who underwent seroconversion and 28
      unexposed blood donors. Main results were: NK cell lytic activities against both
      the NK-susceptible K562 cell line and the NK-resistant Daudi cell line were
      significantly augmented in EU IDUs compared with either controls or
      seroconverters before or after seroconversion; NK cells producing the cytokines
      IFN-gamma and TNF-alpha and the beta chemokines CCL3, CCL4, and CCL5 were also
      increased in the EU IDUs, either after in vitro activation or without
      stimulation. The finding of an enhanced NK cell function in EU IDUs, especially
      compared with IDUs who became HIV-1 infected, supports the hypothesis that NK
      cells contribute to the protection against HIV-1 infection.

PMID- 14634072
TI  - Cutting edge: efficient MHC class I cross-presentation during early vaccinia
      infection requires the transfer of proteasomal intermediates between antigen
      donor and presenting cells.
AB  - Priming of CD8(+) T cells requires presentation of short peptides bound to MHC
      class I molecules of professional APCs. Cross-presentation is a mechanism whereby
      professional APC present on their own MHC class I molecules peptides derived from
      degradation of Ags synthesized by other Ag "donor cells." The mechanism of cross
      presentation is poorly understood, and the nature of the transferred Ag is
      unknown. In this report, we demonstrate that the bulk of a cross-presented Ag
      transferred from donor cells recently infected with vaccinia virus are
      proteasomal products that are susceptible to peptidases within the donor cell
      cytosol and not full-length proteins or mature epitopes either free or bound to
      chaperones.

PMID- 14634073
TI  - Cutting edge: transplantation tolerance through enhanced CTLA-4 expression.
AB  - Knockout and blocking studies have shown a critical role for CTLA-4 in peripheral
      tolerance, however, it is unknown whether augmenting CTLA-4 expression actually
      promotes tolerance. Here we demonstrate a specific and requisite role for CTLA-4
      and its up-regulation in tolerance through anti-CD45RB. First, long-term murine
      islet allograft survival induced by anti-CD45RB is prevented by CTLA4-Ig, which
      interferes with B7:CTLA-4 interactions. Second, anti-CD45RB is ineffective in
      recipients lacking CTLA-4, B7-1, and B7-2. In contrast, CTLA4-Ig, which targets
      B7 on allogeneic cells, promotes long-term engraftment in these mice. Moreover,
      anti-CD45RB was effective in B7-deficient controls expressing CTLA-4. Finally, in
      wild-type mice, CTLA-4 expression returned to baseline 17 days after receiving
      anti-CD45RB, and was refractory to further increase. Transplantation and anti
      CD45RB therapy at this time could neither augment CTLA-4 nor prolong engraftment.
      These data demonstrate a specific role for CTLA-4 in anti-CD45RB-mediated
      tolerance and indicate that CTLA-4 up-regulation can directly promote allograft
      survival.

PMID- 14634074
TI  - Cutting edge: self-peptides drive the peripheral expansion of CD4+CD25+
      regulatory T cells.
AB  - CD4(+)CD25(+) regulatory T cell selection is initiated by high-specificity
      interactions with self-peptides in the thymus, although how these cells respond
      to cytokine-derived signals and to re-exposure to self-peptide:MHC complexes in
      the periphery is not well understood. We have used a transgenic mouse system, in
      which the peptide that induces thymic selection of a clonal population of
      CD4(+)CD25(+) regulatory T cells is known, to show that CD4(+)CD25(+) T cells
      proliferate in response to their selecting self-peptide in vivo. Moreover, they
      do not proliferate in response to lymphopenia in the absence of the selecting
      self-peptide, reflecting a low level of expression of the high affinity receptor
      for IL-7 (CD127) relative to conventional CD4(+) T cells. That their selecting
      self-peptide is both required for and promotes the peripheral expansion of
      CD4(+)CD25(+) regulatory T cells may direct their accumulation in sites where the
      self-peptide is expressed.

PMID- 14634075
TI  - Cutting edge: TCR contacts as anchors: effects on affinity and HLA-DM stability.
AB  - Peptides presented via the class II MHC (MHCII) pathway are selected based on
      affinity for MHCII and stability in the presence of HLA-DM. Currently, epitope
      selection is thought to be controlled by the ability of peptide to sequester
      "anchor" residues into pockets in the MHCII. Residues exhibiting higher levels of
      solvent accessibility have been shown to contact TCR, but their roles in affinity
      and complex stability have not been directly studied. Using the HLA-DR1-binding
      influenza peptide, hemagglutinin (306-318), as a model, we show that side chain
      substitutions at these positions influence affinity and HLA-DM stability.
      Multiple substitutions reduce affinity to a greater extent than the loss of the
      major P1 anchor residue. We propose that these effects may be mediated through
      the H-bond network. These results demonstrate the importance of solvent-exposed
      residues in epitope selection and blur the distinctions between anchor and TCR
      contact residues.

PMID- 14634076
TI  - Requirements for T cell-polarized tubulation of class II+ compartments in
      dendritic cells.
AB  - Activation of naive CD4 T cells by dendritic cells requires the sequential
      interaction of many TCR molecules with peptide-class II complexes of the
      appropriate specificity. Such interaction results in morphological transformation
      of class II MHC-containing endosomal compartments. In this study, we analyze the
      requirements for long tubular endosomal structures that polarize toward T cell
      contact sites using dendritic cells from I-A(b) class II -enhanced green
      fluorescent protein knock-in mice and I-A(b)-restricted CD4 T cells specific for
      OVA. Clustering of membrane proteins and ligation of T cell adhesion molecules
      LFA-1 and CD2 are involved in induction of endosomal tubulation. Activation of T
      cells increases their ability to induce class II-enhanced green fluorescent
      protein-positive tubules in dendritic cells, in part through up-regulation of
      CD40 ligand. Remarkably, and in stark contrast with the result obtained with
      dendritic cells loaded with intact OVA, OVA peptide added to dendritic cells
      failed to evoke T cell-polarized endosomal tubulation even though both conditions
      allowed T cell stimulation. These results suggest the existence of microdomains
      on the membrane of dendritic cells that allow Ag-specific T cells to evoke
      tubulation in the dendritic cell.

PMID- 14634077
TI  - CD4+ T cell-associated pathophysiology critically depends on CD18 gene dose
      effects in a murine model of psoriasis.
AB  - In a CD18 hypomorphic polygenic PL/J mouse model, the severe reduction of CD18
      (beta(2) integrin) to 2-16% of wild-type levels leads to the development of a
      psoriasiform skin disease. In this study, we analyzed the influence of reduced
      CD18 gene expression on T cell function, and its contribution to the pathogenesis
      of this disease. Both CD4(+) and CD8(+) T cells were significantly increased in
      the skin of affected CD18 hypomorphic mice. But only depletion of CD4(+) T cells,
      and not the removal of CD8(+) T cells, resulted in a complete clearance of the
      psoriasiform dermatitis. This indicates a central role of CD4(+) T cells in the
      pathogenesis of this disorder, further supported by the detection of several Th1
      like cytokines released predominantly by CD4(+) T cells. In contrast to the CD18
      hypomorphic mice, CD18 null mutants of the same strain did not develop the
      psoriasiform dermatitis. This is in part due to a lack of T cell emigration from
      dermal blood vessels, as experimental allergic contact dermatitis could be
      induced in CD18 hypomorphic and wild-type mice, but not in CD18 null mutants.
      Hence, 2-16% of CD18 gene expression is obviously sufficient for T cell
      emigration driving the inflammatory phenotype in CD18 hypomorphic mice. Our data
      suggest that the pathogenic involvement of CD4(+) T cells depends on a gene dose
      effect with a reduced expression of the CD18 protein in PL/J mice. This murine
      inflammatory skin model may also have relevance for human polygenic inflammatory
      diseases.

PMID- 14634078
TI  - CD40, but not CD154, expression on B cells is necessary for optimal primary B
      cell responses.
AB  - CD40 is an important costimulatory molecule for B cells as well as dendritic
      cells, monocytes, and other APCs. The ligand for CD40, CD154, is expressed on
      activated T cells, NK cells, mast cells, basophils, and even activated B cells.
      Although both CD40(-/-) and CD154(-/-) mice have impaired ability to isotype
      switch, form germinal centers, make memory B cells, and produce Ab, it is not
      entirely clear whether these defects are intrinsic to B cells, to other APCs, or
      to T cells. Using bone marrow chimeric mice, we investigated whether CD40 or
      CD154 must be expressed on B cells for optimal B cell responses in vivo. We
      demonstrate that CD40 expression on B cells is required for the generation of
      germinal centers, isotype switching, and sustained Ab production, even when other
      APCs express CD40. In contrast, the expression of CD154 on B cells is not
      required for the generation of germinal centers, isotype switching, or sustained
      Ab production. In fact, B cell responses are completely normal when CD154
      expression is limited exclusively to Ag-specific T cells. These results suggest
      that the interaction of CD154 expressed by activated CD4 T cells with CD40
      expressed by B cells is the primary pathway necessary to achieve B cell
      activation and differentiation and that CD154 expression on B cells does not
      noticeably facilitate B cell activation and differentiation.

PMID- 14634079
TI  - Tethering of apoptotic cells to phagocytes through binding of CD47 to Src
      homology 2 domain-bearing protein tyrosine phosphatase substrate-1.
AB  - Apoptotic cells are swiftly phagocytosed by macrophages and immature dendritic
      cells. In this study, we found that one mouse macrophage cell line (BAM3)
      engulfed apoptotic thymocytes, but not a lymphoma cell line (WR19L). mAbs that
      inhibited the phagocytosis of apoptotic thymocytes by BAM3 were identified.
      Purification of the Ag revealed that it was Src homology 2 domain-bearing protein
      tyrosine phosphatase substrate-1 (SHPS-1). CD47, the ligand for SHPS-1, was
      expressed in mouse thymocytes, but not in WR19L. When WR19L was transformed with
      CD47, the transformants, after induction of apoptosis, could be phagocytosed by
      BAM3. The WR19L transformants expressing CD47 were more efficiently engulfed in
      vivo by splenic dendritic cells than the parental WR19L. Masking of the
      phosphatidylserine exposed on apoptotic thymocytes inhibited the engulfment,
      whereas the anti-SHPS-1 mAb inhibited not only the engulfment, but also the
      binding of apoptotic cells to phagocytes. These results indicate that macrophages
      require CD47 and phosphatidylserine on apoptotic cells for engulfment, and
      suggest that the interaction between CD47 and SHPS-1 works as a tethering step in
      the phagocytosis.

PMID- 14634080
TI  - IL-2 is not required for the initiation of CD8 T cell cycling but sustains
      expansion.
AB  - Based primarily on in vitro data, IL-2 is believed to be the key cytokine for
      initiation of the cell cycle of activated T cells. However, the role of IL-2
      remains unresolved for T cell responses in vivo. We examined whether the absence
      of IL-2-mediated signaling in CD8 T cells affected initiation of proliferation.
      Our results conclusively demonstrated that initial division of Ag-specific CD8 T
      cells following priming was IL-2 independent, regardless of the context in which
      Ag was presented. In contrast, the latter stage of the proliferative phase was IL
      2-dependent, particularly in nonlymphoid tissues. Thus, activated CD8 T cells
      initially undergo IL-2-independent proliferation, but reach a critical juncture
      where the requirement for IL-2 as a growth factor gains prominence.

PMID- 14634081
TI  - Aberrant extracellular and dendritic cell (DC) surface expression of heat shock
      protein (hsp)70 in the rheumatoid joint: possible mechanisms of hsp/DC-mediated
      cross-priming.
AB  - We describe, in rheumatoid arthritis (RA), abnormalities in the expression and
      distribution of heat shock protein (hsp) and dendritic cells (DCs) that are
      conducive to cross-priming and DC cross-talk. As detected by ELISA, inducible
      (i)hsp70 was dramatically increased in RA synovial fluid (RASF) vs normal human
      and RA sera and osteoarthritis and gout synovial fluid. Immunoblot analysis of
      fresh RASF cells revealed marked increases in ihsp70 and activation of its
      transcription factor heat shock factor-1, compared with fresh normal peripheral
      blood cells. Flow cytometry and microscopy demonstrated high levels of ihsp70 on
      the surface of RASF myeloid DCs (but not normal myeloid DCs) that occurred
      concurrently with hspRs (CD91/CD14). ihsp70 present in RASF exhibited chaperoning
      potential, as indicated by the capture of ihsp70 present in RASF on the surface
      of normal DCs. Binding was partially competitively inhibited by excess alpha(2)
      macroglobulin, indicating that hspRs in addition to CD91 participate in the
      capture process. These data indicate that ihsp70 may chaperone autologous Ags
      into immature RASF DCs via hspRs, and that cross-talk between DCs coexpressing
      hsp/hspRs reflects a disease process in RA. The induction of surface ihsp70 on
      normal cells after sublethal heat stress and the release of ihsp70 from normal
      DCs after inflammatory stress also suggest that the pattern of ihsp70 expression
      in RASF occurs in response to sustained stress.

PMID- 14634082
TI  - Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice
      develop an exacerbated neural antigen-induced Th1 response and experimental
      allergic encephalomyelitis.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear
      receptor transcription factor that regulates cell growth, differentiation, and
      homeostasis. PPARgamma agonists are potent therapeutic agents for type 2
      diabetes, obesity, and inflammation. Experimental allergic encephalomyelitis
      (EAE) is a Th1 cell-mediated inflammatory demyelinating autoimmune disease model
      of multiple sclerosis. We have shown recently that PPARgamma agonists inhibit EAE
      by blocking IL-12 production, IL-12 signaling, and neural Ag-induced Th1
      differentiation. In this study, we show that the PPARgamma-deficient heterozygous
      mice develop an exacerbated EAE with prolonged clinical symptoms than the wild
      type littermates, following immunization with myelin oligodendrocyte glycoprotein
      (MOG) p35-55 peptide. The exacerbation of EAE in PPARgamma(+/-) mice associates
      with an increased expansion of CD4(+) and CD8(+) T cells and expression of CD40
      and MHC class II molecules in response to MOGp35-55 Ag. The PPARgamma(+/-) mice
      also showed an increase in T cell proliferation and Th1 response to MOGp35-55 Ag
      than the wild-type littermates. These findings suggest that PPARgamma be a
      critical physiological regulator of CNS inflammation and demyelination in EAE and
      perhaps multiple sclerosis and other Th1 cell-mediated autoimmune diseases.

PMID- 14634083
TI  - TNF receptor-associated factor 6 deficiency during hemopoiesis induces Th2
      polarized inflammatory disease.
AB  - Toll-like receptors (TLR) initiate rapid innate immune responses by recognizing
      microbial products. These events in turn lead to the development of an efficient
      adaptive immune response through the up-regulation of a number of costimulatory
      molecules, including members of the TNF/TNFR superfamily, on the surface of an
      APC. TNFR-associated factor 6 (TRAF6) is a common signaling adapter used by
      members of both the TNFR and the TLR/IL-1R superfamilies, and as such plays a
      critical role in the development of immune responses. As TRAF6-deficient mice die
      prematurely, we generated chimeras reconstituted with TRAF6-deficient fetal liver
      cells to analyze functions of TRAF6 in vivo in the hemopoietic compartment. We
      found that TRAF6-deficient chimeras develop a progressive lethal inflammatory
      disease associated with massive organ infiltration and activation of CD4(+) T
      cells in a Th2-polarized phenotype, and a defect in IL-18 responsiveness. When
      recombination-activating gene 2(-/-) blastocysts were complemented with TRAF6
      deficient embryonic stem cells, a marked elevation of activated CD4(+) T cells
      and progressive inflammatory disease were also observed. Moreover, T cell
      activation and lethal inflammation were not reversed in mixed chimeric mice
      generated from normal and TRAF6-deficient fetal liver cells. These results
      suggest that deletion of TRAF6 induces a dominant Th2-type polarized autoimmune
      response. Therefore, in addition to playing a critical role in innate and
      adaptive immunity, TRAF6 is likely to play a previously unrecognized role in the
      maintenance of self-tolerance.

PMID- 14634085
TI  - In vitro differentiation from naive to mature E-selectin binding CD4 T cells:
      acquisition of skin-homing properties occurs independently of cutaneous
      lymphocyte antigen expression.
AB  - We previously showed that skin-homing CD4 T cells in peripheral blood can be
      subdivided into three populations on the basis of the expression pattern of the
      cutaneous lymphocyte Ag (CLA) and fucosyltransferase VII (FucT-VII): FucT
      VII(+)CLA(-), FucT-VII(+)CLA(+), and FucT-VII(-)CLA(+). In view of the known late
      appearance of CLA during T cell differentiation, T cells programmed to attain
      skin-homing properties may start to generate E-selectin-binding epitopes at early
      stages of differentiation before induction of CLA expression. To this end, the in
      vitro differentiation from naive to CLA(+) memory T cells was followed after
      activation with anti-CD3 mAb. Here we demonstrate that naive skin-homing CD4 T
      cell precursors undergo a linear differentiation process from the FucT-VII(+)CLA(
      ) phenotype to the FucT-VII(+)CLA(+) phenotype and eventually to the FucT-VII(
      )CLA(+) phenotype. The appearance of the FucT-VII(+)CLA(-) subset coincided with
      or could be immediately followed by the generation of E-selectin binding
      epitopes, and even after E-selectin-binding epitopes were no longer detectable,
      CLA remained expressed for prolonged periods of time, suggesting that induction
      of functional E-selectin ligands depends primarily on the expression of FucT-VII,
      but not CLA. Immunofluorescence and confocal microscopy studies of these T cells
      confirm that most E-selectin ligands were found independently of CLA expression.

PMID- 14634084
TI  - Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy,
      nonallergic individuals.
AB  - We investigated the capacity of CD25(+) T regulatory cells (Treg) to modulate T
      cell responses to nickel, a common cause of allergic contact dermatitis. CD4(+) T
      cells isolated from the peripheral blood of six healthy, nonallergic individuals
      showed a limited capacity to proliferate in response to nickel in vitro, but
      responsiveness was strongly augmented (mean increment +/- SD, 240 +/- 60%) when
      cells were depleted of CD25(+) Treg. Although CD25(+) Treg were anergic to
      nickel, a small percentage up-regulated membrane CTLA-4 upon nickel exposure.
      CD25(+) Treg strongly and dose-dependently inhibited nickel-specific activation
      of CD25(-) T lymphocytes in coculture experiments in a cytokine-independent, but
      cell-to-cell contact-dependent, manner. Approximately 30% of circulating CD25(+)
      Treg expressed the cutaneous lymphocyte-associated Ag (CLA), and CLA(+)CD25(+)
      Treg were more efficient than CLA(-)CD25(+) cells in suppressing nickel
      responsiveness of CD25(-) T cells. The site of a negative patch test in response
      to nickel showed an infiltrate of CD4(+)CLA(+) cells and CD25(+) cells, which
      accounted for approximately 20% of the total T cells isolated from the tissue.
      Skin-derived T cells suppressed nickel-specific responses of peripheral blood
      CD25(-) T cells. In addition, 60 +/- 14% of peripheral blood CD25(+) Treg
      expressed the chemokine receptor CCR7 and strongly inhibited naive T cell
      activation in response to nickel. Finally, CD25(+) T cells isolated from
      peripheral blood of nickel-allergic patients showed a limited or absent capacity
      to suppress metal-specific CD4(+) and CD8(+) T cell responses. The results
      indicates that in healthy individuals CD25(+) Treg can control the activation of
      both naive and effector nickel-specific T cells.

PMID- 14634086
TI  - Ultraviolet B radiation-induced cell death: critical role of ultraviolet dose in
      inflammation and lupus autoantigen redistribution.
AB  - The nuclear self-Ags targeted in systemic lupus erythematosus translocate to the
      cell membrane of UV-irradiated apoptotic keratinocytes and may represent an
      important source of self-immunization. It is hard to understand how the
      noninflammatory milieu accompanying most apoptosis might provoke an immunogenic
      response leading to autoantibodies. We have found that the precise amount of
      keratinocyte UV exposure is crucial in determining the rate of apoptosis, the
      amount of inflammatory cytokine production, and the degree of autoantigen
      translocation. Low doses of UVB (</=15 mJ/cm(2)) promptly induced a normal,
      caspase-dependent apoptosis, while intermediate doses of UV-B (35 mJ/cm(2))
      caused apoptosis with altered morphology, slower DNA fragmentation, and poly(ADP
      ribose) polymerase degradation accompanied by increased Bcl-2. High doses of UVB
      (80 mJ/cm(2)) induced instead necrosis. We observed IL-1 production upon
      intermediate and high UVB doses. Nuclear Ag redistribution was also markedly UV
      dose dependent: at low doses, Sm, Ku, and DNA translocated to the surfaces of
      early apoptotic cells. At intermediate doses, these Ags concentrated on the cell
      membrane when the nucleus was still visible. At high doses, these autoantigens
      diffused into the cytoplasm and were released into the supernatant. Taken
      together, the results show that low-dose UVB induces prompt noninflammatory
      apoptosis. In contrast, intermediate and high doses of UVB induce proinflammatory
      apoptosis and necrosis, where the production of inflammatory cytokines is
      accompanied by exposure and release of autoantigens. The key importance of the UV
      dose on the fate of apoptotic keratinocytes and on their potential immunogenicity
      should help clarify the role of UVB in inducing systemic lupus erythematosus
      autoimmunity.

PMID- 14634087
TI  - Human ErbB-2 (Her-2) transgenic mice: a model system for testing Her-2 based
      vaccines.
AB  - Her-2 transgenic (Tg) mice were generated with wild-type human c-ErbB-2 (Her-2)
      under the whey acidic protein promoter. They are tolerant to Her-2 and
      appropriate for testing Her-2 vaccines. The expression of transmembrane ErbB-2
      from the whey acidic protein-Her-2 cassette and its up-regulation by insulin and
      hydrocortisone was verified by in vitro transfection. The transgene cassette was
      microinjected into fertilized eggs from B6C3 (C3H x C57BL/6) females mated with
      B6C3 males. Transgene-positive mice were backcrossed onto C57BL/6 mice. Human
      ErbB-2 was expressed in the secretory mammary epithelia during pregnancy and
      lactation and expressed constitutively in the Bergman glia cells within the
      molecular layer of the cerebellum. Overt, neoplastic transformation was not
      detected in any tissue examined. Tolerance to Her-2 was demonstrated by
      inoculating mice with a syngenic tumor expressing high levels of human ErbB-2.
      Tumors grew exclusively in Her-2 Tg mice without inducing an Ab response, while
      the nontransgenic littermates remained tumor free for 10 mo and mounted a robust
      anti-ErbB-2 Ab response. When immunized five times with plasmid DNA encoding
      secErbB-2 and GM-CSF, respectively, approximately 33% of the Her-2 Tg mice
      rejected a lethal challenge of EL-4/E2 tumor cells, whereas all immunized
      littermates rejected the tumor. Therefore, Her-2 Tg mice express human ErbB-2 in
      the brain and mammary gland and demonstrated tolerance to ErbB-2 which was
      partially overcome by DNA vaccination. The breakable tolerance of Her-2 Tg mice
      resembles that in human and these mice are particularly suited for testing human
      ErbB-2 based vaccines.

PMID- 14634088
TI  - Increased severity of murine lupus in female mice is due to enhanced expansion of
      pathogenic T cells.
AB  - A strong female predominance is a well-recognized feature of human lupus. The
      mechanism by which sex influences disease expression and severity is not fully
      understood. To address this question, we used the parent-into-F(1) (p-->F(1))
      model of chronic graft-vs-host disease (cGVHD) in which lupus-like humoral
      autoimmunity and renal disease are induced in normal F(1) mice. An advantage of
      this model is that the pathogenic T cells driving disease (donor strain) can be
      studied separately from nonspecifically activated T cells (host strain). We
      observed that lupus-like disease using female donor and host mice (f-->F cGVHD)
      is characterized by more severe long-term disease (glomerulonephritis) than with
      male donor and host (m-->M cGVHD). Interestingly, differences in disease
      parameters could be seen at 2 wk after parental cell transfer, as evidenced by a
      2- to 3-fold greater engraftment of donor CD4(+) T cells in f-->F cGVHD mice,
      which persisted throughout disease course. Enhanced engraftment of donor CD4(+) T
      cells in f-->F cGVHD mice was not due to differences in splenic homing,
      alloreactive precursor frequency, initial proliferation rates, or apoptotic
      rates, but rather to sustained high proliferation rates during wk 2 of disease
      compared with m-->M cGVHD mice. Crossover studies (m-->F, f-->M) demonstrated
      that enhanced donor CD4(+) T cell proliferation and engraftment segregate with
      the sex of the host. These results demonstrate that the sex of the recipient can
      influence the expansion of pathogenic T cells, thus increasing long-term the
      burden of autoreactive T cells and resulting in greater disease severity.

PMID- 14634089
TI  - Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer
      in activation-induced cell death of brain microglia.
AB  - Mouse brain microglial cells undergo apoptosis on exposure to inflammatory
      stimuli, which is considered as an autoregulatory mechanism to control their own
      activation. Here, we present evidence that an antiproliferative B cell
      translocation gene 1 (BTG1) constitutes a novel apoptotic pathway of LPS/IFN
      gamma-activated microglia. The expression of BTG1 was synergistically enhanced by
      LPS and IFN-gamma in BV-2 mouse microglial cells as well as in primary microglia
      cultures. Levels of BTG1 expression inversely correlated with a proliferative
      capacity of the microglial cells. Tetracycline-based conditional expression of
      BTG1 not only suppressed microglial proliferation but also increased the
      sensitivity of microglial cells to NO-induced apoptosis, suggesting a novel
      mechanism of cooperation between LPS and IFN-gamma in the induction of microglial
      apoptosis. An increase in BTG1 expression, however, did not affect microglial
      production of NO, TNF-alpha, or IL-1beta, indicating that the antiproliferative
      BTG1 is important in the activation-induced apoptosis of microglia, but not in
      the activation itself. The synergistic action of LPS and IFN-gamma in the
      microglial BTG1 induction and apoptosis was dependent on the Janus kinase/STAT1
      pathway, but not IFN-regulatory factor-1, as demonstrated by a pharmacological
      inhibitor of Janus kinase (AG490), STAT1 dominant negative mutant, and IFN
      regulatory factor-1-deficient mice. Taken together, antiproliferative BTG1 may
      participate in the activation-induced cell death of microglia by lowering the
      threshold for apoptosis; BTG1 increases the sensitivity of microglia to
      apoptogenic action of autocrine cytotoxic mediator, NO. Our results point out an
      important link between the proliferative state of microglia and their sensitivity
      to apoptogenic agents.

PMID- 14634090
TI  - MHC class II-peptide complexes in dendritic cell lipid microdomains initiate the
      CD4 Th1 phenotype.
AB  - We investigated differentiation of CD4 T cells responding to Ag presented by bone
      marrow-derived dendritic cells (DC) in association with MHC class II (MHC II)
      molecules. Peptides encapsulated in liposomes opsonized by IgG were taken up by
      endocytosis. MHC II-peptide-specific T cells responding to this Ag were polarized
      to a Th1 cytokine profile in a CD40-, CD28-, MyD88-, and IL-12-dependent manner.
      Th2 responses were obtained from the same transgenic T cell population exposed to
      the same DC on which MHC-peptide complexes had dispersed for 48 h following
      uptake of FcR-targeted liposomes. DC that took up the same FcR-targeted liposomes
      and then were exposed to methyl-beta-cyclodextrin, which chelates cholesterol and
      dissociates lipid microdomains, also stimulated Th2 differentiation. Incubation
      of T cells with DC incubated with peptides directly binding to MHC II resulted in
      Th2 responses, whether or not the DC were coincubated with opsonized liposomes as
      a maturation stimulus. CD4 Th1 polarization thus appears to depend on MHC II
      peptide complex clustering in DC lipid microdomains and the time between peptide
      loading and T cell encounter.

PMID- 14634091
TI  - Estradiol treatment redirects the isotype of the autoantibody response and
      prevents the development of autoimmune arthritis.
AB  - A number of clinical and experimental observations have been made relating
      elevated estrogen levels with the amelioration of autoimmune diseases, yet
      questions remain about the levels required for efficacy as well as the mechanism
      of disease inhibition. Using the collagen-induced arthritis (CIA) model, we have
      studied the effects of physiological, sustained levels of 17beta-estradiol in
      preventing the development of autoimmune arthritis and analyzed the changes in
      the autoimmune response. Using time-release pellets of 17beta-estradiol,
      arthritis development was significantly inhibited in three different strains of
      CIA-susceptible mice compared with the effect of placebo treatment, and serum
      estradiol levels similar to those of mice in estrus were found to be equally
      effective as higher estradiol concentrations. Analysis of the autoimmune response
      in the estradiol-treated mice indicated that T cell production of IFN-gamma was
      markedly decreased, and significant decreases were also observed in levels of IL
      10 and GM-CSF produced by lymph nodes cells from estradiol-treated mice. Although
      the total IgG anti-CII response was only minimally affected by estrogen
      treatment, a significant reduction in the levels of IgG2a anti-CII Abs and an
      increase in the levels of IgG1 anti-CII Abs were observed in estradiol-treated
      mice. These data indicate that estradiol treatment altered the Th profile of the
      autoimmune T cell response, which, in turn, altered the production of IgG Abs to
      an isotype that is poor at fixing complement, an important component in the
      immunopathogenesis of CIA.

PMID- 14634092
TI  - The duration of signaling through CD40 directs biological ability of dendritic
      cells to induce antitumor immunity.
AB  - Although it has been demonstrated that the functions of dendritic cells (DCs),
      including Ag capture, Ag presentation, and migratory activity, change dynamically
      with their maturation, the most appropriate conditioning of DCs for anticancer
      immunotherapy is still unclear. The help signal is one of the most potent stimuli
      for DC maturation and is provided by the interaction of CD40 expressed on DCs
      with CD40 ligand on CD4(+) T cells. To elucidate the appropriate conditioning of
      DCs for anticancer immunotherapy, we examined the biological activity of DCs
      stimulated with immobilized anti-CD40 Ab. DCs stimulated for 3 h (3h-DCs) still
      showed an immature phenotype, but exhibited augmented migration toward secondary
      lymphoid tissues. Subcutaneous injection of 3h-DCs facilitated priming of T
      cells, which could mediate potent antitumor therapeutic efficacy, in draining
      lymph nodes and successfully induced protective immunity. In contrast, 24h-DCs
      showed a mature phenotype with good Ag presentation ability to induce cell
      killing by adoptively transferred CD8(+) T cells when injected at tumor sites;
      however, they showed no migratory activity and were unable to induce protective
      immunity when injected s.c. This is the first report that functionally distinct
      DCs, either for the priming phase or for the effector phase, could be obtained by
      conditioning with CD40 stimulation and that the duration of stimulation
      determines the biological outcome. The usage of DCs conditioned for the priming
      phase might provide significant advantages in anticancer immunotherapy.

PMID- 14634093
TI  - Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like
      receptor 4-dependent mechanism.
AB  - The biology of pathogen-associated molecular patterns (PAMPs) stimulating APCs to
      differentiate into a Th1-promoting phenotype has been well characterized.
      Conversely, not a single pathogen product that promotes a Th2 phenotype has been
      rigorously identified. Strong Th2 responses and dendritic cell 2 maturation are
      driven by helminth extracts, and carbohydrates have been shown to be responsible
      for much of this activity. In this study, we show that a helminth carbohydrate,
      lacto-N-fucopentaose III (LNFPIII) functions as an innate Th2 promoter via its
      action on murine dendritic cells, with the alpha1-3-linked fucose required for
      this activity. In contrast to Th1-type PAMPs, which activate extracellular signal
      regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein
      kinases, the Th2 PAMP LNFPIII preferentially activates extracellular signal
      regulated kinase. Furthermore, the ability of LNFPIII to drive DC2 maturation is
      dependent on signaling via Toll-like receptor 4. These data support a new
      understanding of how APCs integrate signaling pathways to produce a Th1- or Th2
      promoting phenotype.

PMID- 14634094
TI  - Dendritic cell-induced activation of adaptive and innate antitumor immunity.
AB  - While studying Ag-pulsed syngeneic dendritic cell (DC) immunization, we
      discovered that surprisingly, unpulsed DCs induced protection against tumor lung
      metastases resulting from i.v. injection of a syngeneic BALB/c colon carcinoma
      CT26 or a syngeneic C57BL/6 lung carcinoma LL/2. Splenocytes or immature splenic
      DCs did not protect. The protection was mediated by NK cells, in that it was
      abrogated by treatment with anti-asialo-GM1 but not anti-CD8, and was induced by
      CD1(-/-) DCs unable to stimulate NKT cells, but did not occur in beige mice
      lacking NK cells. Protection correlated with increased NK activity, and increased
      infiltration of NK but not CD8(+) cells in lungs of tumor-bearing mice.
      Protection depended on the presence of costimulatory molecules CD80, CD86, and
      CD40 on the DCs, but surprisingly did not require DCs that could make IL-12 or IL
      15. Unexpectedly, protection sensitive to anti-asialo-GM1 and increased NK
      activity were still present 14 mo after DC injection. As NK cells lack memory, we
      found by depletion that CD4(+) not CD8(+) T cells were required for induction of
      the NK antitumor response. The role of DCs and CD4(+) T cells provides a novel
      mechanism for NK cell induction and innate immunity against cancer that may have
      potential in preventing clinical metastases.

PMID- 14634095
TI  - Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis:
      development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells.
AB  - Using transgenic mice that express a constitutively active version of STAT5b, we
      demonstrate that STAT5 plays a key role in governing B cell development and T
      cell homeostasis. STAT5 activation leads to a 10-fold increase in pro-B, but not
      pro-T, cells. Conversely, STAT5 signaling promotes the expansion of mature
      alphabeta T cells (6-fold increase) and gammadelta and NK T cells (3- to 4-fold
      increase), but not of mature B cells. In addition, STAT5 activation has
      dramatically divergent effects on CD8(+) vs CD4(+) T cells, leading to the
      selective expansion of CD8(+) memory-like T cells and CD4(+)CD25(+) regulatory T
      cells. These results establish that activation of STAT5 is the primary mechanism
      underlying both IL-7/IL-15-dependent homeostatic proliferation of naive and
      memory CD8(+) T cells and IL-2-dependent development of CD4(+)CD25(+) regulatory
      T cells.

PMID- 14634096
TI  - Systemic administration of IL-18 promotes diabetes development in young nonobese
      diabetic mice.
AB  - IL-18 is now identified as a pleiotropic cytokine that acts as a cofactor for
      both Th1 and Th2 cell development. Type 1 diabetes is considered a Th1-type
      autoimmune disease, and to date, the suppressive effect of exogenous IL-18 on the
      development of diabetes has been reported in 10-wk-old nonobese diabetic (NOD)
      mice. In the present study we administered exogenous IL-18 systemically in 4-wk
      old NOD mice using i.m. injection of the IL-18 expression plasmid DNA (pCAGGS-IL
      18) with electroporation. Contrary to previous reports, the incidence of diabetes
      development was significantly increased in NOD mice injected with pCAGGS-IL-18
      compared with that in control mice. Systemic and pancreatic cytokine profiles
      deviated to a Th1-dominant state, and the the frequency of glutamic acid
      decarboxylase-reactive IFN-gamma-producing CD4(+) cells was also high in the IL
      18 group. Moreover, it was suggested that the promoting effect of IL-18 might be
      associated with increased peripheral IL-12, CD86, and pancreatic IFN-inducible
      protein-10 mRNA expression levels. In conclusion, we demonstrate here that IL-18
      plays a promoting role as an enhancer of Th1-type immune responses in diabetes
      development early in the spontaneous disease process, which may contribute to
      elucidating the pathogenesis of type 1 diabetes.

PMID- 14634097
TI  - Ligation of CD27 on B cells in vivo during primary immunization enhances
      commitment to memory B cell responses.
AB  - Ligation of CD27 on B cells has been shown to inhibit terminal differentiation of
      activated murine B cells into plasma cells. We show in this study that this
      inhibition is accompanied by an enhanced movement of activated B cells toward
      differentiation into memory cells. Treatment of mice with anti-CD27 during
      immunization leads to the generation of greater numbers of Ag-binding B cells in
      draining lymph nodes that persist for longer periods of time, and they contain a
      greater proportion of cells of a postgerminal center phenotype. Limiting dilution
      analyses reveal that they contain a higher frequency of cells that can be
      stimulated to secrete specific IgG, and adoptive transfer experiments confirm
      that they can generate higher secondary responses in carrier-primed recipients.
      Remarkably, significant secondary responses are also seen following primary
      immunization with a T-independent Ag in the presence of anti-CD27, confirming
      that ligation of CD27 on B cells during priming induces differentiation into the
      memory lineage. Treatment with anti-CD27 during priming also increases the
      average affinity of the secondary response, suggesting that high affinity clones
      generated early in a primary response may normally differentiate preferentially
      into plasma cells and are rescued from this fate by CD27 ligation. Anti-CD40
      treatment shows similar effects in vivo. However, unlike CD27, CD40 coligation
      also enhances proliferation, survival, and isotype switching of LPS-stimulated B
      cells, suggesting that the two receptors may enhance commitment to B cell memory
      by different mechanisms, or that a common mechanism is used through both
      receptors that does not involve cell cycle control or survival.

PMID- 14634098
TI  - Fibronectin-associated Fas ligand rapidly induces opposing and time-dependent
      effects on the activation and apoptosis of T cells.
AB  - Recently, it has been shown that Fas ligand (FasL) interacts with the
      extracellular matrix (ECM) protein fibronectin (FN), and that the bound FasL
      retains its cytotoxic efficacy. Herein, we examined the ramifications of FasL-ECM
      protein interactions throughout a specific time period, in the absence or
      presence of additional activating molecules, assuming that these complexed
      interactions occur during inflammation. We found that exposure of purified human
      T cells to FN-associated recombinant FasL for as brief as 5-10 min at 0.1-100
      ng/ml induced their adhesion in beta(1) integrin- and FasR-dependent manners
      while activating the intracellular protein kinase, Pyk-2. The FN-associated FasL
      stops the CXCL12 (stromal cell-derived factor 1alpha)-induced chemotaxis of T
      cells by inhibiting the chemokine-induced extracellular signal-regulated kinase
      signaling and cytoskeletal rearrangement. This short term exposure of T cells to
      the FN-bound FasL (1 ng/ml), which was followed by T cell activation via the CD3
      complex, resulted in 1) increased secretion of IFN-gamma (measured after 24 h),
      and 2) enhanced T cell apoptosis (measured after 72 h). Thus, in the context of
      inflamed ECM and depending on the time after FasL activation, its concentration,
      and the nature of other contextual mediators, FasL initially retains effector T
      cells at sites of inflammation and, later, induces T cell apoptosis and return to
      homeostasis.

PMID- 14634099
TI  - Tolerance through indifference: autoreactive B cells to the nuclear antigen La
      show no evidence of tolerance in a transgenic model.
AB  - Systemic autoimmune diseases are characterized by the production of high titer
      autoantibodies specific for ubiquitous nuclear self-Ags such as DNA, Sm, and La
      (SS-B), so the normal mechanisms of B cell tolerance to disease-associated
      nuclear Ags have been of great interest. Mechanisms of B cell tolerance include
      deletion, anergy, developmental arrest, receptor editing, and B cell
      differentiation to the B-1 subtype. However, recent studies in our laboratory
      have suggested that B cell tolerance to the nuclear autoantigen La is limited in
      normal mice, and tolerance may reside primarily in the T cell compartment. To
      test this hypothesis, we created Ig transgenic mice expressing the IgM H chain
      from an mAb specific for a xenogeneic epitope within human La (hLa). These mice
      were bred with hLa-transgenic mice that constitutively express hLa in a manner
      comparable to endogenous mouse La. Between 5-15% of transgenic B cells developing
      in the absence of hLa were specific for hLa, and these cells were neither
      depleted nor developmentally arrested in the presence of endogenous hLa
      expression. Instead, these autoreactive B cells matured normally and
      differentiated into Ab-forming cells, capable of secreting high titer
      autoantibody. Additionally, the life span of autoreactive hLa-specific B cells
      was not reduced, and they were phenotypically and functionally indistinguishable
      from naive nonautoreactive hLa-specific B cells developing in the absence of hLa.
      Together these data suggest a lack of intrinsic B cell tolerance involving any
      known mechanisms indicating that these autoreactive B cells are indifferent to
      their autoantigen.

PMID- 14634100
TI  - IL-4 and IL-13 induce SOCS-1 gene expression in A549 cells by three functional
      STAT6-binding motifs located upstream of the transcription initiation site.
AB  - Proteins of the suppressors of cytokine signaling (SOCS) family have important
      functions as negative regulators of cytokine signaling. We show here that SOCS-1
      expression can be induced in the human epithelial lung cell line A549 by IL-4 and
      IL-13. Analysis of reporter gene constructs under control of the SOCS-1 promoter
      provides evidence that IL-4- and IL-13-induced up-regulation is dependent on
      three IFN-gamma-activated sequence motifs of the sequence TTC(N)(4)GAA, which is
      known for binding STAT6. The three motifs are situated close to each other
      approximately 600 bp upstream of the transcriptional initiation site. When
      mutations were inserted into all three IFN-gamma-activated sequence motifs at the
      same time, IL-4-IL-13-induced luciferase activity was abrogated. With single and
      double mutants, promoter activity was diminished in comparison with the wild-type
      promoter. STAT6 is therefore required for IL-4-IL-13-dependent SOCS-1 expression
      in A549 cells, and the three identified binding motifs cooperate to induce
      maximal transcription. EMSAs conducted with nuclear extracts of IL-4- and IL-13
      stimulated A549 cells showed that STAT6 was able to bind to each of the three
      binding motifs. Finally, cotransfection of a SOCS-1 expression vector inhibited
      activation of SOCS-1 promoter luciferase constructs. Thus, SOCS-1 is able to
      autoregulate its expression via a negative feedback loop.

PMID- 14634101
TI  - Vaccination with plasmid DNA activates dendritic cells via Toll-like receptor 9
      (TLR9) but functions in TLR9-deficient mice.
AB  - We analyzed whether the immunobiology of vaccinating plasmid DNA containing a
      transcription unit for OVA is influenced by immunostimulatory CpG motifs in the
      plasmid backbone. Indeed, plasmid DNA differentially activated in vitro myeloid
      and plasmacytoid dendritic cells (DCs) provided they expressed the CpG-DNA
      receptor, Toll-like receptor 9 (TLR9). Dependent on the DC subset, activation
      resulted in type 1 IFN production, while both DC subsets produced IL-6 and up
      regulated expression of costimulatory molecules CD40 and CD86. In vivo, however,
      even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and
      clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and
      TLR9- or MyD88-negative mice. Overall, these results negate a dominant role of
      CpG-DNA/TLR9 interactions in long-term vaccination protocols.

PMID- 14634102
TI  - Control of NKT cell differentiation by tissue-specific microenvironments.
AB  - CD1d-restricted Valpha14 NKT cells play an important role in both Th1- and Th2
      type immune responses. To determine whether NKT cells develop two functionally
      distinct subsets that provoke different types of responses, we examined the
      phenotypes and cellular functions of NK1.1(+) and DX5(+) T cells. We found that
      both NK1.1(+) and DX5(+) T cells are CD1d-restricted Valpha14 T cells with
      identical Ag specificities, phenotypes, tissue locations, and functions. Similar
      to the NK1.1 marker, the DX5 marker (CD49b) is expressed on mature NKT cells in
      both NK1.1 allele-positive and allele-negative strains. However, when NK1.1(+)
      and DX5(+) NKT cells isolated from different tissues were compared, we found that
      thymic and splenic NKT cells differed not only in their cytokine profiles, but
      also in their phenotype and requirements for costimulatory signals. Thymic NKT
      cells displayed the phenotype of activated T cells and could be fully activated
      by TCR ligation. In contrast, splenic NKT cells displayed the phenotype of memory
      T cells and required a costimulatory signal for activation. Furthermore, the
      function and phenotype of thymic and splenic NKT cells were modulated by APCs
      from various tissues that expressed different levels of costimulatory molecules.
      Modulation of NKT cell function and differentiation may be mediated by synergic
      effects of costimulatory molecules on the surface of APCs. The results of the
      present study suggest that the costimulatory signals of tissue-specific APCs are
      key factors for NKT cell differentiation, and these signals cannot be replaced by
      anti-CD28 or anti-CD40 ligand Abs.

PMID- 14634103
TI  - CD19 function in early and late B cell development. II. CD19 facilitates the pro
      B/pre-B transition.
AB  - Proliferative expansion of pro-B cells is an IL-7-dependent process that allows
      for the rearrangement of H chain genes and the expression of the pre-B cell
      receptor (pre-BCR). Further B cell differentiation is dependent upon signals
      elicited through the pre-BCR, which are thought to be responsible for allelic
      exclusion, induced L chain gene rearrangement, and continued proliferation. CD19
      promotes the proliferation and survival of mature B cells, but its role in early
      B cell development is less well understood. Here we identify and characterize
      impairments in early B cell development in CD19(-/-) mice. Following sublethal
      irradiation, we found decreased numbers of autoreconstituted early B cells, which
      was first evident in the large cycling pre-B cell fraction. Reduced cell
      progression due to a defect in proliferation was made evident from cell cycle
      analysis and bromodeoxyuridine labeling of bone marrow cells from CD19(-/-) and
      wild-type mice. Studies of IL-7-dependent pre-B cell cultures derived from wild
      type and CD19(-/-) mouse bone marrow suggested that CD19 has little affect on IL
      7 signaling. By contrast, signaling through the pre-BCR was impaired in the
      absence of CD19, as demonstrated by reduced activation of Bruton's tyrosine
      kinase and extracellular signal-regulated kinase/mitogen-activated protein
      kinase. Thus, in addition to promoting mature B cell homeostasis and Ag-induced
      responses, the early onset of CD19 expression acts to enhance B cell generation.

PMID- 14634104
TI  - CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with
      IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor
      immunity elicited by peptide vaccination.
AB  - CD25(+) regulatory T (T reg) cells suppress the activation/proliferation of other
      CD4(+) or CD8(+) T cells in vitro. Also, down-regulation of CD25(+) T reg cells
      enhance antitumor immune responses. In this study, we show that depletion of
      CD25(+) T reg cells allows the host to induce both CD4(+) and CD8(+) antitumoral
      responses following tumor challenge. Simultaneous depletion of CD25(+) and CD8(+)
      cells, as well as adoptive transfer experiments, revealed that tumor-specific
      CD4(+) T cells, which emerged in the absence of CD25(+) T reg cells, were able to
      reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral
      effect mediated by CD4(+) T cells was dependent on IFN-gamma production, which
      exerted a potent antiangiogenic activity. The capacity of the host to mount this
      antitumor response is lost once the number of CD25(+) T reg cells is restored
      over time. However, CD25(+) T reg cell depletion before immunization with AH1 (a
      cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a
      long-lasting antitumoral immune response, not observed if immunization is
      conducted in the presence of regulatory cells. A study of the effect of different
      levels of depletion of CD25(+) T reg cells before immunization with the peptide
      AH1 alone, or in combination with a Th determinant, unraveled that Th cells play
      an important role in overcoming the suppressive effect of CD25(+) T reg on the
      induction of long-lasting cellular immune responses.

PMID- 14634105
TI  - Dendritic cells charged with apoptotic tumor cells induce long-lived protective
      CD4+ and CD8+ T cell immunity against B16 melanoma.
AB  - Dendritic cells (DCs) are potent APCs and attractive vectors for cancer
      immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor
      that expresses low levels of MHC class I products, we investigated whether DCs
      loaded ex vivo with apoptotic tumor cells could elicit combined CD4(+) and CD8(+)
      T cell dependent, long term immunity following injection into mice. The bone
      marrow-derived DCs underwent maturation during overnight coculture with apoptotic
      melanoma cells. Following injection, DCs migrated to the draining lymph nodes
      comparably to control DCs at a level corresponding to approximately 0.5% of the
      injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against
      an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free
      12 wk after challenge. CD4(+) and CD8(+) T cells were efficiently primed in
      vaccinated animals, as evidenced by IFN-gamma secretion after in vitro
      stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally
      expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma
      cells were recognized by immune CD8(+) T cells in vitro, and cytolytic activity
      against tyrosinase-related protein 2(180-188)-pulsed target cells was observed in
      vivo. When either CD4(+) or CD8(+) T cells were depleted at the time of
      challenge, the protection was completely abrogated. Mice receiving a tumor
      challenge 10 wk after vaccination were also protected, consistent with the
      induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing
      apoptotic death can prime melanoma-specific helper and CTLs and provide long term
      protection against a poorly immunogenic tumor in mice.

PMID- 14634106
TI  - Promiscuity of MHC class Ib-restricted T cell responses.
AB  - Murine infection with the Gram-positive intracellular bacterium Listeria
      monocytogenes activates CD8(+) T cells that recognize bacterially derived N
      formyl methionine peptides in the context of H2-M3 MHC class Ib molecules. Three
      peptides, fMIGWII, fMIVIL, and fMIVTLF, are targets of L. monocytogenes-specific
      CD8(+) T cells. To investigate epitope cross-recognition by H2-M3-restricted
      CD8(+) T cells, we deleted the sequence encoding fMIGWII from a virulent strain
      of L. monocytogenes. Infection with fMIGWII-deficient L. monocytogenes
      unexpectedly primed CD8(+) T cells that stain with fMIGWII/H2-M3 tetramers and
      lyse fMIGWII-coated target cells in vivo. Because the fMIGWII sequence is
      nonredundant, we speculated that other bacterially derived Ags are priming these
      responses. HPLC peptide fractionation of bacterial culture supernatants revealed
      several distinct L. monocytogenes-derived peptides that are recognized by fMIGWII
      specific T cells. Our results demonstrate that the dominant H2-M3-restricted
      CD8(+) T cell population, although reactive with fMIGWII, is primed by other, non
      fMIGWII peptides derived from L. monocytogenes. Although this degree of Ag
      receptor promiscuity is unusual for the adaptive immune system, it may be a more
      common feature of T cell responses restricted by nonpolymorphic MHC class Ib
      molecules.

PMID- 14634107
TI  - Molecular cloning and immunologic characterization of a novel cDNA coding for
      progesterone-induced blocking factor.
AB  - Previous studies from our laboratory showed that the immunomodulatory effects of
      progesterone are mediated by a 34-kDa protein, named the progesterone-induced
      blocking factor (PIBF). Lymphocytes of women with threatened abortion fail to
      produce this factor. Via inducing a Th2 biased cytokine production and blocking
      of NK activity, PIBF prevents induced pregnancy loss in mice, suggesting that
      substitution therapy with PIBF could be useful as an alternative treatment of
      certain forms of recurrent spontaneous abortions. Our study was aimed at mapping
      the sequence and structure of PIBF coding cDNA and characterizing the encoded
      protein product. Screening of a human liver cDNA library revealed a 2765-bp clone
      with a 2271-bp open reading frame. The PIBF1 cDNA encodes a protein of 757 amino
      acid residues with an 89-kDa predicted molecular mass, which shows no significant
      amino acid sequence homology with any known protein. PIBF produced via
      recombinant technique is recognized by the Ab specific for the secreted
      lymphocyte PIBF Ab, and possesses the biological activities of the secreted
      lymphocyte PIBF. The full-length PIBF is associated with the nucleus, whereas
      secretion of shorter forms, such a 34-kDa protein is induced by activation of the
      cell. The 48-kDa N-terminal part of PIBF is biologically active, and the part of
      the molecule, responsible for modulating NK activity is encoded by exons 2-4.
      These data provide an initial step for exploiting the possible diagnostic and
      therapeutic potential of this immunomodulatory molecule.

PMID- 14634108
TI  - Simultaneous prediction of binding capacity for multiple molecules of the HLA B44
      supertype.
AB  - We selected for study a set of B44-supertype molecules collectively represented
      in >40% of the individuals in all major ethnicities (B*1801, B*4001, B*4002,
      B*4402, B*4403, and B*4501). The peptide-binding specificity of each molecule was
      characterized using single amino acid substitution analogues and nonredundant
      peptide libraries. In all cases, only peptide ligands with glutamic acid in
      position 2 were preferred. At the C terminus, each allele was associated with a
      unique but broad pattern of preferences, but all molecules tolerated
      hydrophobic/aliphatic (leucine, isoleucine, valine, methionine), aromatic
      (tyrosine, phenylalanine, tryptophan), and small (alanine, glycine, threonine)
      residues. Secondary anchor motifs were also defined for all molecules. Together,
      these features were used to define a B44 supermotif and a novel algorithm for
      calculating degeneracy scores that can be used to predict B44-supertype
      degenerate binders. Approximately 90% of the peptides with a B44 supermotif
      degeneracy score of >10 bound at least three of the six B44-supertype molecules
      studied with high affinity. Finally, a number of peptides derived from hepatitis
      B and C viruses, HIV, and Plasmodium falciparum have been identified that have
      degenerate B44 supertype-binding capacity. Taken together, these findings have
      important implications for epitope-based approaches to vaccination,
      immunotherapy, and the monitoring of immune responses.

PMID- 14634109
TI  - Altered regulation of Fc gamma RII on aged follicular dendritic cells correlates
      with immunoreceptor tyrosine-based inhibition motif signaling in B cells and
      reduced germinal center formation.
AB  - Aging is associated with reduced trapping of Ag in the form of in immune
      complexes (ICs) by follicular dendritic cells (FDCs). We postulated that this
      defect was due to altered regulation of IC trapping receptors. The level of FDC
      M1, complement receptors 1 and 2, FcgammaRII, and FDC-M2 on FDCs was
      immunohistochemically quantitated in draining lymph nodes of actively immunized
      mice for 10 days after Ag challenge. Initially, FDC FcgammaRII levels were
      similar but by day 3 a drastic reduction in FDC-FcgammaRII expression was
      apparent in old mice. FDC-M2 labeling, reflecting IC trapping, was also reduced
      and correlated with a dramatic reduction in germinal center (GC) B cells as
      indicated by reduced GC size and number. Nevertheless, labeling of FDC reticula
      with FDC-M1 and anti-complement receptors 1 and 2 was preserved, indicating that
      FDCs were present. FDCs in active GCs normally express high levels of FcRs that
      are thought to bind Fc portions of Abs in ICs and minimize their binding to FcRs
      on B cells. Thus, cross-linking of B cell receptor and FcR via IC is minimized,
      thereby reducing signaling via the immunoreceptor tyrosine-based inhibition
      motif. Old FDCs taken at day 3, when they lack FcgammaRII, were incapable of
      preventing immunoreceptor tyrosine-based inhibition motif signaling in wild-type
      B cells but old FDCs stimulated B cells from FcgammaRIIB(-/-) mice to produce
      near normal levels of specific Ab. The present data support the concept that FcR
      are regulated abnormally on old FDCs. This abnormality correlates with a reduced
      IC retention and with a reduced capacity of FDCs to present ICs in a way that
      will activate GC B cells.

PMID- 14634110
TI  - Function of Bruton's tyrosine kinase during B cell development is partially
      independent of its catalytic activity.
AB  - The Tec family member Bruton's tyrosine kinase (Btk) is a cytoplasmic protein
      tyrosine kinase that transduces signals from the pre-B and B cell receptor (BCR).
      Btk is involved in pre-B cell maturation by regulating IL-7 responsiveness, cell
      surface phenotype changes, and the activation of lambda L chain gene
      rearrangements. In mature B cells, Btk is essential for BCR-mediated
      proliferation and survival. Upon BCR stimulation, Btk is transphosphorylated at
      position Y551, which promotes its catalytic activity and subsequently results in
      autophosphorylation at position Y223 in the Src homology 3 domain. To address the
      significance of Y223 autophosphorylation and the requirement of enzymatic
      activity for Btk function in vivo, we generated transgenic mice that express the
      autophosphorylation site mutant Y223F and the kinase-inactive mutant K430R,
      respectively. We found that Y223 autophosphorylation was not required for the
      regulation of IL-7 responsiveness and cell surface phenotype changes in
      differentiating pre-B cells, or for peripheral B cell differentiation. However,
      expression of the Y223F-Btk transgene could not fully rescue the reduction of
      lambda L chain usage in Btk-deficient mice. In contrast, transgenic expression of
      kinase-inactive K430R-Btk completely reconstituted lambda usage in Btk-deficient
      mice, but the defective modulation of pre-B cell surface markers, peripheral B
      cell survival, and BCR-mediated NF-kappaB induction were partially corrected.
      From these findings, we conclude that: 1) autophosphorylation at position Y223 is
      not essential for Btk function in vivo, except for regulation of lambda L chain
      usage, and 2) during B cell development, Btk partially acts as an adapter
      molecule, independent of its catalytic activity.

PMID- 14634111
TI  - OX40-mediated memory T cell generation is TNF receptor-associated factor 2
      dependent.
AB  - Tumor necrosis factor receptor-associated factor 2 (TRAF2), an adapter protein
      that associates with the cytoplasmic tail of OX40, may play a critical role in
      OX40-mediated signal transduction. To investigate the in vivo role of TRAF2 in
      OX40-mediated generation of Ag-specific memory T cells, we bred OVA-specific TCR
      transgenic mice to TRAF2 dominant-negative (TRAF2 DN) mice. Following Ag
      stimulation and OX40 engagement of TRAF2 DN T cells in vivo, the number of long
      lived OVA-specific T cells and effector T cell function was dramatically reduced
      when compared with wild-type T cells. We also demonstrate that CTLA-4 is down
      regulated following OX40 engagement in vivo and the OX40-specific TRAF2 DN defect
      was partially overcome by CTLA-4 blockade in vivo. The data provide evidence that
      TRAF2 is linked to OX40-mediated memory T cell expansion and survival, and point
      to the down-regulation of CTLA-4 as a possible control element to enhance early T
      cell expansion through OX40 signaling.

PMID- 14634112
TI  - Ikaros family members from the agnathan Myxine glutinosa and the urochordate
      Oikopleura dioica: emergence of an essential transcription factor for adaptive
      immunity.
AB  - The Ikaros multigene family encodes a number of zinc finger transcription factors
      that play key roles in vertebrate hemopoietic stem cell differentiation and the
      generation of B, T, and NK cell lineages. In this study, we describe the
      identification and characterization of an Ikaros family-like (IFL) protein from
      the agnathan hagfish Myxine glutinosa and the marine urochordate Oikopleura
      dioica, both of which lie on the evolutionary boundary between the vertebrates
      and invertebrates. The IFL molecules identified in these animals displayed high
      conservation in the zinc finger motifs critical for DNA binding and dimerization
      in comparison with those of jawed vertebrates. Expression of the IFL gene in
      hagfish was strongest in blood, intestine, and gills. In O. dioica, transcription
      from the IFL gene was initiated at or around the time of hatching and maintained
      throughout the life span of the animal. In situ hybridization localized O. dioica
      IFL expression to the Fol cells, which are responsible for generating the food
      filter of the house. Biochemical analysis of the DNA binding and dimerization
      domains from M. glutinosa and O. dioici IFLs showed that M. glutinosa behaves as
      a true Ikaros family member. Taken together, these results indicate that the
      properties associated with the Ikaros family preceded the emergence of the jawed
      vertebrates and thus adaptive immunity.

PMID- 14634113
TI  - Inhibition of NF-kappa B activation and its target genes by heparin-binding
      epidermal growth factor-like growth factor.
AB  - Many cells upon injury mount extensive, compensatory responses that increase cell
      survival; however, the intracellular signals that regulate these responses are
      not completely understood. Heparin-binding epidermal growth factor-like growth
      factor (HB-EGF) has been implicated as a cytoprotective agent. We have previously
      demonstrated that pretreatment of human intestinal epithelial cells with HB-EGF
      significantly decreased cytokine-induced activation of inducible NO synthase mRNA
      expression and NO production and protected the cells from apoptosis and necrosis.
      However, the mechanisms by which HB-EGF exerts these effects are not known. Here
      we show that cytokine exposure (IL-1beta and IFN-gamma) induced NF-kappaB
      activation and IL-8 and NO production in DLD-1 cells. Transient expression of a
      dominant negative form of IkappaBalpha decreased NO production, suggesting that
      the cytokines stimulated NO production in part through activation of NF-kappaB.
      HB-EGF dramatically suppressed NF-kappaB activity and IL-8 release and decreased
      NO production in cells pretreated with HB-EGF. HB-EGF blocked NF-kappaB
      activation by inhibiting IkappaB kinase activation and IkappaB phosphorylation
      and degradation, thus interfering with NF-kappaB nuclear translocation, DNA
      binding activity, and NF-kappaB-dependent transcriptional activity. The data
      demonstrate that HB-EGF decreases inflammatory cytokine and NO production by
      interfering with the NF-kappaB signaling pathway. Inhibition of NF-kappaB may
      represent one of the mechanisms by which HB-EGF exerts its potent anti
      inflammatory and cytoprotective effects.

PMID- 14634114
TI  - Allogeneic T cells treated with amotosalen prevent lethal cytomegalovirus disease
      without producing graft-versus-host disease following bone marrow
      transplantation.
AB  - Infusion of donor antiviral T cells can provide protective immunity for
      recipients of hemopoietic progenitor cell transplants, but may cause graft-vs
      host disease (GVHD). Current methods of separating antiviral T cells from the
      alloreactive T cells that produce GVHD are neither routine nor rapid. In a model
      of lethal murine CMV (MCMV) infection following MHC-mismatched bone marrow
      transplantation, infusion of MCMV-immune donor lymphocytes pretreated with the
      DNA cross-linking compound amotosalen prevented MCMV lethality without producing
      GVHD. Although 95% of mice receiving 30 x 10(6) pretreated donor lymphocytes
      survived beyond day +100 without MCMV disease or GVHD, all mice receiving
      equivalent numbers of untreated lymphocytes rapidly died of GVHD. In vitro,
      amotosalen blocked T cell proliferation without suppressing MCMV peptide-induced
      IFN-gamma production by MCMV-primed CD8(+) T cells. In vivo, pretreated
      lymphocytes reduced hepatic MCMV load by 4-log(10) and promoted full hemopoietic
      chimerism. Amotosalen-treated, MCMV tetramer-positive memory (CD44(high)) CD8(+)
      T cells persisted to day +100 following infusion, and expressed IFN-gamma when
      presented with viral peptide. Pretreated T cells were effective at preventing
      MCMV lethality over a wide range of concentrations. Thus, amotosalen treatment
      rapidly eliminates the GVHD activity of polyclonal T cells, while preserving long
      term antiviral and graft facilitation effects, and may be clinically useful for
      routine adoptive immunotherapy.

PMID- 14634115
TI  - Activation of antigen-specific CD8 T cells results in minimal killing of
      bystander bacteria.
AB  - Memory CD8 T cells play a critical role in protective immunity against
      intracellular pathogens. In addition to their ability to specifically recognize
      and lyse infected targets, activated CD8 T cells secrete cytokines that induce
      phagocytic cells to engulf and kill bacterial pathogens. In this study, we asked
      whether activation of Ag-specific CD8 T cells results in nonspecific killing of
      bystander bacteria during a mixed infection. Mice with epitope-specific memory
      CD8 T cells were coinfected with two isogenic strains of recombinant Listeria
      monocytogenes that differ in the cognate epitope. Recall responses by epitope
      specific CD8 T cells rapidly inhibited the growth of epitope-bearing bacteria,
      impeding the course of infection within 6 h after challenge. This rapid
      inhibition was highly specific and did not affect the growth of coinfecting
      bacteria without the epitope. CTL recall did not enhance activation of innate
      immune cells, as evidenced by the absence of inducible NO synthase production in
      infectious foci. Our observations demonstrate the remarkable specificity of the
      bactericidal mechanisms of CTL and reveal the possibility for escape mutants to
      prevail in the hostile environment of a specific immune response. This
      implication has a bearing on subunit vaccine design strategies and understanding
      failure of immunization against bacterial infection.

PMID- 14634116
TI  - NK cells respond to pulmonary infection with Mycobacterium tuberculosis, but play
      a minimal role in protection.
AB  - Both innate and adaptive immune systems contribute to host defense against
      infection with Mycobacterium tuberculosis. NK cells have been associated with
      early resistance against intracellular pathogens and are known to be potent
      producers of the cytokine IFN-gamma. In C57BL/6 mice infected by aerosol exposure
      with M. tuberculosis, NK cells increased in the lungs over the first 21 days of
      infection. Expansion of the NK cell subset was associated with increased
      expression of activation and maturation markers. In addition, NK cells isolated
      from the infected lungs were capable of producing IFN-gamma and became positive
      for perforin. In vivo depletion of NK cells using a lytic Ab had no influence on
      bacterial load within the lungs. These findings indicate that NK cells can become
      activated during the early response to pulmonary tuberculosis in the mouse model
      and are a source of IFN-gamma, but their removal does not substantially alter the
      expression of host resistance.

PMID- 14634117
TI  - Human C-reactive protein does not protect against acute lipopolysaccharide
      challenge in mice.
AB  - The physiological and pathophysiological functions of C-reactive protein (CRP),
      the classical acute-phase protein, are not well established, despite many reports
      of biological effects of CRP in vitro and in model systems in vivo. Limited,
      small scale experiments have suggested that rabbit and human CRP may both protect
      mice against lethal toxicity of Gram-negative bacterial LPS. However, in
      substantial well-controlled studies in C57BL/6 mice challenged with Escherichia
      coli O111:B4 LPS, we show in this work that significant protection against
      lethality was conferred neither by an autologous acute-phase response to sterile
      inflammatory stimuli given to wild-type mice 24 h before LPS challenge, nor by
      human CRP, whether passively administered or expressed transgenically. Male mice
      transgenic for human CRP, which mount a major acute-phase response of human CRP
      after LPS injection, were also not protected against the lethality of LPS from
      either E. coli O55:B5 or Salmonella typhimurium. Even when the acute-phase human
      CRP response was actively stimulated in transgenic mice before LPS challenge, no
      protection against LPS toxicity was observed. Indeed, male mice transgenic for
      human CRP that were pretreated with casein to stimulate an acute-phase response
      24 h before LPS challenge suffered significantly greater mortality than
      unstimulated human CRP transgenic controls. Rather than being protective in this
      situation, human CRP may thus have pathogenic proinflammatory effects in vivo.

PMID- 14634118
TI  - Cross-talk in the innate immune system: neutrophils instruct recruitment and
      activation of dendritic cells during microbial infection.
AB  - Type I inflammatory cytokines are essential for immunity to many microbial
      pathogens, including Toxoplasma gondii. Dendritic cells (DC) are key to
      initiating type 1 immunity, but neutrophils are also a source of chemokines and
      cytokines involved in Th1 response ignition. We found that T. gondii triggered
      neutrophil synthesis of CC chemokine ligand (CCL)3, CCL4, CCL5, and CCL20,
      chemokines that were strongly chemotactic for immature DC. Moreover, supernatants
      obtained from parasite-stimulated polymorphonuclear leukocytes induced DC IL
      12(p40) and TNF-alpha production. Parasite-triggered neutrophils also released
      factors that induced DC CD40 and CD86 up-regulation, and this response was
      dependent upon parasite-triggered neutrophil TNF-alpha production. In vivo
      evidence that polymorphonuclear leukocytes exert an important influence on DC
      activation was obtained by examining splenic DC cytokine production following
      infection of neutrophil-depleted mice. These animals displayed severely curtailed
      splenic DC IL-12 and TNF-alpha production, as revealed by ex vivo flow cytometric
      analysis and in vitro culture assay. Our results reveal a previously unrecognized
      regulatory role for neutrophils in DC function during microbial infection, and
      suggest that cross-talk between these cell populations is an important component
      of the innate immune response to infection.

PMID- 14634119
TI  - Sustained nitric oxide delivery delays nitric oxide-dependent apoptosis in
      macrophages: contribution to the physiological function of activated macrophages.
AB  - Treatment of the macrophage cell line RAW 264.7 with the short-lived NO donor S
      nitrosoglutathione triggers apoptosis through the release of mitochondrial
      mediators. However, continuous supply of NO by long-lived NO donors protected
      cells from apoptosis through mechanisms that involved the maintenance or an
      increase in the levels of the inhibitor of apoptosis proteins (IAPs) cIAP-1, cIAP
      2, and xIAP and decreases in the accumulation of p53 and in the levels and
      targeting of Bax to the mitochondria. As a result of these changes, the
      activation of caspases 9 and 3 was notably delayed, expanding the time of
      viability of the macrophages. Moreover, inhibition of NO synthase 2 activity
      after 8 h of stimulation of RAW 264.7 cells with LPS and IFN-gamma accelerated
      apoptosis via an increase in the processing and activation of caspases. These
      data suggest that NO exerts an important role in the autoregulation of apoptosis
      in macrophages.

PMID- 14634120
TI  - IL-1R-associated kinase 4 is required for lipopolysaccharide-induced activation
      of APC.
AB  - The bacterial product LPS is a critical stimulus for the host immune system in
      the response against the corresponding bacterial infection. LPS provides an
      activation stimulus for macrophages and a maturation signal for dendritic cells
      to set up innate and adaptive immune responses, respectively. The signaling
      cascade of myeloid differentiation factor 88-->IL-1R-associated kinase (IRAK)-
      >TNFR-associated factor 6 has been implicated in mediating LPS signaling. In this
      report, we studied the function of IRAK-4 in various LPS-induced signals. We
      found that IRAK-4-deficient cells were severely impaired in producing some IFN
      regulated genes as well as inflammatory cytokines in response to LPS. Among the
      critical downstream signaling pathways induced by LPS, NF-kappaB activation but
      not IFN regulatory factor 3 or STAT1 activation was defective in cells lacking
      IRAK-4. IRAK-4 was also required for the proper maturation of dendritic cells by
      LPS stimulation, particularly in terms of cytokine production and the ability to
      stimulate Th cell differentiation. Our results demonstrate that IRAK-4 is
      critical for the LPS-induced activations of APCs.

PMID- 14634121
TI  - Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation
      of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia.
AB  - Curcumin has been strongly implicated as an anti-inflammatory agent, but the
      precise mechanisms of its action are largely unknown. In this study, we show that
      the inhibitory action of curcumin on Janus kinase (JAK)-STAT signaling can
      contribute to its anti-inflammatory activity in the brain. In both rat primary
      microglia and murine BV2 microglial cells, curcumin effectively suppressed the
      ganglioside-, LPS-, or IFN-gamma-stimulated induction of cyclooxygenase-2 and
      inducible NO synthase, important enzymes that mediate inflammatory processes.
      These anti-inflammatory effects appear to be due, at least in part, to the
      suppression of the JAK-STAT inflammatory signaling cascade. Curcumin markedly
      inhibited the phosphorylation of STAT1 and 3 as well as JAK1 and 2 in microglia
      activated with gangliosides, LPS, or IFN-gamma. Curcumin consistently suppressed
      not only NF binding to IFN-gamma-activated sequence/IFN-stimulated regulatory
      element, but also the expression of inflammation-associated genes, including ICAM
      1 and monocyte chemoattractant protein 1, whose promoters contain STAT-binding
      elements. We further show that activation of Src homology 2 domain-containing
      protein tyrosine phosphatases (SHP)-2, a negative regulator of JAK activity, is
      likely to be one of the mechanisms underlying the curcumin-mediated inhibition of
      JAK-STAT signaling. Treatment of microglial cells with curcumin led to an
      increase in phosphorylation and association with JAK1/2 of SHP-2, which inhibit
      the initiation of JAK-STAT inflammatory signaling in activated microglia. Taken
      together, these data suggest curcumin suppresses JAK-STAT signaling via
      activation of SHP-2, thus attenuating inflammatory response of brain microglial
      cells.

PMID- 14634122
TI  - Cyclooxygenase-2-derived E prostaglandins down-regulate matrix metalloproteinase
      1 expression in fibroblast-like synoviocytes via inhibition of extracellular
      signal-regulated kinase activation.
AB  - We examined the regulation of matrix metalloproteinase (MMP) production by
      mitogen-activated protein kinases and cyclooxygenases (COXs) in fibroblast-like
      synoviocytes (FLSCs). IL-1beta and TNF-alpha stimulated FLSC extracellular signal
      regulated kinase (ERK) activation as well as MMP-1 and -13 release. Pharmacologic
      inhibitors of ERK inhibited MMP-1, but not MMP-13 expression. Whereas millimolar
      salicylates inhibited both ERK and MMP-1, nonsalicylate COX and selective COX-2
      inhibitors enhanced stimulated MMP-1 release. Addition of exogenous PGE(1) or
      PGE(2) inhibited MMP-1, reversed the effects of COX inhibitors, and inhibited ERK
      activation, suggesting that COX-2 activity tonically inhibits MMP-1 production
      via ERK inhibition by E PGs. Exposure of FLSCs to nonselective COX and selective
      COX-2 inhibitors in the absence of stimulation resulted in up-regulation of MMP-1
      expression in an ERK-dependent manner. Moreover, COX inhibition sufficient to
      reduce PGE levels increased ERK activity. Our data indicate that: 1) ERK
      activation mediates MMP-1 but not MMP-13 release from FLSCs, 2) COX-2-derived E
      PGs inhibit MMP-1 release from FLSCs via inhibition of ERK, and 3) COX
      inhibitors, by attenuating PGE inhibition of ERK, enhance the release of MMP-1 by
      FLSC.

PMID- 14634123
TI  - Fc gamma RIIIb allele-sensitive release of alpha-defensins: anti-neutrophil
      cytoplasmic antibody-induced release of chemotaxins.
AB  - Antineutrophil cytoplasmic Abs (ANCA) can activate neutrophils in an FcgammaR
      dependent manner, but the link between this ANCA-induced effect and mononuclear
      cell activation with the characteristic granuloma formation of Wegener's
      granulomatosis is unclear. Human alpha-defensins, small cationic antimicrobial
      peptides, are found in neutrophils and have chemotactic activity for T cells,
      dendritic cells, and monocytes. In this study, we quantitated the release of
      alpha-defensins (human neutrophil peptides 1-3) from human neutrophils after
      targeted FcgammaR cross-linking (XL). Homotypic XL of FcgammaRIIa, FcgammaRIIIb,
      or heterotypic XL of both receptors resulted in significant release of alpha
      defensins, an effect also induced by both human polyclonal and murine monoclonal
      cytoplasmic staining ANCA (anti-proteinase 3). This release of alpha-defensins,
      as well as of other granule constituents (ANCA targets anti-proteinase 3 and
      myeloperoxidase and elastase), was significantly greater in donors homozygous for
      the NA1 allele of FcgammaRIIIb than in donors homozygous for NA2. Interestingly,
      the ANCA-induced release was completely inhibited by the IgG Fc-binding peptide
      TG19320, which blocks the IgG-Fc region from binding to FcgammaR. Based on their
      chemotactic properties, alpha-defensins and their release by ANCA may contribute
      to modulation of the acquired immune response and to granuloma formation. The
      greater activity of the FcgammaRIIIB-NA1 genotype may also explain the greater
      severity of disease and its flare-ups in patients with this allele.

PMID- 14634124
TI  - Activation of endothelial extracellular signal-regulated kinase is essential for
      neutrophil transmigration: potential involvement of a soluble neutrophil factor
      in endothelial activation.
AB  - During an inflammatory response induced by infection or injury, leukocytes
      traverse the endothelial barrier into the tissue space. Extravasation of
      leukocytes is a multistep process involving rolling, tethering, firm adhesion to
      the endothelium, and finally, transendothelial migration, the least characterized
      step in the process. The resting endothelium is normally impermeable to
      leukocytes; thus, during inflammation, intracellular signals that modulate
      endothelial permeability are activated to facilitate the paracellular passage of
      leukocytes. Using a static in vitro assay of neutrophil transmigration across
      human umbilical vein endothelium, a panel of inhibitors of intracellular
      signaling was screened for their ability to inhibit transmigration. PD98059, a
      specific inhibitor of extracellular signal-regulated kinase (ERK) 1/2 activation,
      inhibited both transmigration across TNF-alpha-activated endothelium and
      transmigration induced by the chemoattractant fMLP in a dose-dependent manner.
      PD98059 did not inhibit neutrophil chemotaxis in the absence of an endothelial
      barrier nor neutrophil adhesion to the endothelium, suggesting that its effect
      was on the endothelium, and furthermore, that endothelial ERK activation may be
      important for transmigration. We demonstrate in this study that endothelial ERK
      is indeed activated during neutrophil transmigration and that its activation is
      dependent on the addition of neutrophils to the endothelium. Further
      characterization showed that the trigger for endothelial ERK activation is a
      soluble protein of molecular mass approximately 30 kDa released from neutrophils
      after activation.

PMID- 14634125
TI  - Mac-1, but not LFA-1, uses intercellular adhesion molecule-1 to mediate slow
      leukocyte rolling in TNF-alpha-induced inflammation.
AB  - We have previously shown that Mac-1 and LFA-1 play a cooperative role in slow
      leukocyte rolling in inflamed vessels, and that, although both have a role in
      leukocyte adhesion, the contribution from LFA-1 exceeds that of Mac-1. In this
      study, we used mice deficient in ICAM-1 (ICAM-1(null)) to study the function of
      ICAM-1 as an endothelial ligand for Mac-1 and LFA-1. The cremaster muscles of
      these mice were treated with TNF-alpha and prepared for intravital microscopy. We
      found that the average rolling velocity in venules was not different in ICAM
      1(null) mice (4.7 micro m/s) compared with wild-type mice (5.1 micro m/s).
      Similarly, leukocyte adhesion efficiency in ICAM-1(null) mice (0.11 +/- 0.01 mm)
      was similar to that in Mac-1(-/-) (0.12 +/- 0.03 mm) mice but significantly
      increased compared with that in LFA-1(-/-) (0.08 +/- 0.01 mm) mice and
      significantly reduced from that in wild type (0.26 +/- 0.04 mm). When both LFA-1
      and ICAM-1 were blocked, rolling velocity increased, and adhesion efficiency and
      arrest decreased. However, blocking both Mac-1 and ICAM-1 had no greater effect
      than either blockade alone. We conclude that endothelial ICAM-1 is the main
      ligand responsible for slow leukocyte rolling mediated by Mac-1, but not LFA-1.

PMID- 14634126
TI  - Regulation and phenotype of an innate Th1 cell: role of cytokines and the p38
      kinase pathway.
AB  - We have explored the phenotype and regulation of Th1 cell activation by the
      cytokines IL-12 and IL-18. We demonstrate that these two cytokines selectively
      induce IFN-gamma in a differentiated Th1 cell population through the previously
      described p38 mitogen-activated protein (MAP) kinase pathway. Using a highly
      selective p38 MAP kinase inhibitor, we demonstrate that it is possible to block
      IFN-gamma induction from activated, differentiated Th1 cells via p38 MAP kinase
      without disrupting the activation and differentiation of naive T cells or the
      proliferation of naive or differentiated T cells. In addition, IL-12 and IL-18
      provide an Ag and IL-2-independent survival signal to this uniquely
      differentiated Th1 cell population. We hypothesize that this Ag-independent
      survival of Th1 cells may participate in an innate inflammatory loop with
      monocytes at the sites of chronic inflammation. In addition, p38 MAP kinase
      inhibition of this cytokine-regulated pathway may be a unique mechanism to
      inhibit chronic inflammation without disruption of Ag-driven activation and
      function of naive T cells.

PMID- 14634127
TI  - Fc epsilon RI signaling of mast cells activates intracellular production of
      hydrogen peroxide: role in the regulation of calcium signals.
AB  - Earlier studies, including our own, revealed that activation of mast cells is
      accompanied by production of reactive oxygen species (ROS) that help to mediate
      the release of the inflammatory mediators, including histamine and eicosanoids.
      However, little is known about the mechanisms of ROS production, including the
      species of oxidants produced. In this study we show that in both the RBL-2H3 mast
      cell line and bone marrow-derived mast cells, FcepsilonRI cross-linking
      stimulates intracellular oxidative burst, including hydrogen peroxide (H(2)O(2))
      production, as defined with the oxidant-sensitive dyes dichlorofluorescein and
      scopoletin and the selective scavenger ebselen (2-phenyl-1,2-benzisoselenazol
      3(2H)-one). The oxidative burst was observed immediately after stimulation and
      was most likely due to an NAD(P)H oxidase. Experiments using selective
      pharmacological inhibitors demonstrated that activation of tyrosine kinases and
      phosphatidylinositol-3-kinase is required for induction of the oxidative burst.
      Blockade of the oxidative burst by diphenyleneiodonium impaired the release of
      preformed granular mediators, such as histamine and beta-hexosaminidase, and the
      secretion of newly synthesized leukotriene C(4), whereas selective scavenging
      H(2)O(2) by ebselen impaired leukotriene C(4) secretion, but not degranulation.
      Sustained elevation of cytosolic calcium through store-operated calcium entry was
      totally abolished when ROS production was blocked. In contrast, selective
      depletion of H(2)O(2) caused a considerable decrease and delay of the calcium
      response. Finally, tyrosine phosphorylation of phospholipase Cgamma and the
      linker for activation of T cells, an event required for calcium influx, was
      suppressed by diphenyleneiodonium and ebselen. These studies demonstrate that
      activation of the intracellular oxidative burst is an important regulatory
      mechanism of mast cell responses.

PMID- 14634128
TI  - Increased acute inflammation, leukotriene B4-induced chemotaxis, and signaling in
      mice deficient for G protein-coupled receptor kinase 6.
AB  - Directed migration of polymorphonuclear neutrophils (PMN) is required for
      adequate host defense against invading organisms and leukotriene B(4) (LTB(4)) is
      one of the most potent PMN chemoattractants. LTB(4) exerts its action via binding
      to BLT1, a G protein-coupled receptor. G protein-coupled receptors are
      phosphorylated by G protein-coupled receptor kinases (GRK) in an agonist
      dependent manner, resulting in receptor desensitization. Recently, it has been
      shown that the human BLT1 is a substrate for GRK6. To investigate the
      physiological importance of GRK6 for inflammation and LTB(4) signaling in PMN, we
      used GRK6-deficient mice. The acute inflammatory response (ear swelling and
      influx of PMN into the ear) after topical application of arachidonic acid was
      significantly increased in GRK6(-/-) mice. In vitro, GRK6(-/-) PMN showed
      increased chemokinetic and chemotactic responses to LTB(4). GRK6(-/-) PMN respond
      to LTB(4) with a prolonged increase in intracellular calcium and prolonged actin
      polymerization, suggesting impaired LTB(4) receptor desensitization in the
      absence of GRK6. However, pre-exposure to LTB(4) renders both GRK6(-/-) as well
      as wild-type PMN refractory to restimulation with LTB(4), indicating that the
      presence of GRK6 is not required for this process to occur. In conclusion, GRK6
      deficiency leads to prolonged BLT1 signaling and increased neutrophil migration.

PMID- 14634129
TI  - Endothelial cells proactively form microvilli-like membrane projections upon
      intercellular adhesion molecule 1 engagement of leukocyte LFA-1.
AB  - Specific leukocyte/endothelial interactions are critical for immunity and
      inflammation, yet the molecular details of this interaction interface remain
      poorly understood. Thus, we investigated, with confocal microscopy, the
      distribution dynamics of the central adhesion molecules ICAM-1 and LFA-1 in this
      context. Monolayers of activated HUVECs stained with fluorescent anti-ICAM-1 Fabs
      or Chinese hamster ovary-K1 cells expressing ICAM-1-green fluorescent protein
      were allowed to bind LFA-1-bearing monocytes, neutrophils, or K562 LFA-1
      transfectants. ICAM-1 was rapidly relocalized to newly formed microvilli-like
      membrane projections in response to binding LFA-1 on leukocytes. These ICAM-1
      enriched projections encircled the leukocytes extending up their sides and
      clustered LFA-1 underneath into linear tracks. Projections formed independently
      of VCAM-1/very late Ag 4 interactions, shear, and proactive contributions from
      the LFA-1-bearing cells. In the ICAM-1-bearing endothelial cells, projections
      were enriched in actin but not microtubules, required intracellular calcium, and
      intact microfilament and microtubule cytoskeletons and were independent of
      Rho/Rho kinase signaling. Disruption of these projections with cytochalasin D,
      colchicine, or BAPTA-AM had no affect on firm adhesion. These data show that in
      response to LFA-1 engagement the endothelium proactively forms an ICAM-1-enriched
      cup-like structure that surrounds adherent leukocytes but is not important for
      firm adhesion. This finding leaves open a possible role in leukocyte
      transendothelial migration, which would be consistent with the geometry and
      kinetics of formation of the cup-like structure.

PMID- 14634130
TI  - Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint
      inflammation: critical role of myeloid differentiation factor 88.
AB  - The IL-1R/Toll-like receptor (TLR) superfamily of receptors has a key role in
      innate immunity and inflammation. In this study, we report that streptococcal
      cell wall (SCW)-induced joint inflammation is predominantly dependent on TLR-2
      signaling, since TLR-2-deficient mice were unable to develop either joint
      swelling or inhibition of cartilage matrix synthesis. Myeloid differentiation
      factor 88 (MyD88) is a Toll/IL-1R domain containing adaptor molecule known to
      have a central role in both IL-1R/IL-18R and TLR signaling. Mice deficient for
      MyD88 did not develop SCW-induced arthritis; both joint swelling and disturbance
      of cartilage chondrocyte anabolic function was completely abolished. Local levels
      of proinflammatory cytokines and chemokines in synovial tissue washouts were
      strongly reduced in MyD88-deficient mice. Histology confirmed the pivotal role of
      MyD88 in acute joint inflammation. TLR-2-deficient mice still allow influx of
      inflammatory cells into the joint cavity, although the number of cells was
      markedly reduced. No influx of inflammatory cells was seen in joints of MyD88
      deficient mice. In addition, cartilage matrix proteoglycan loss was completely
      absent in MyD88 knockout mice. These findings clearly demonstrated that MyD88 is
      a key component in SCW-induced joint inflammation. Since agonists of the Toll
      like pathway are abundantly involved in both septic and rheumatoid arthritis,
      targeting of MyD88 may be a novel therapy in inflammatory joint diseases.

PMID- 14634131
TI  - Apoptosis-associated speck-like protein containing a caspase recruitment domain
      is a regulator of procaspase-1 activation.
AB  - Apoptosis-associated speck-like protein containing a caspase recruitment domain
      (ASC)/target of methylation-induced silencing/PYCARD represents one of only two
      proteins encoded in the human genome that contains a caspase recruitment domain
      (CARD) together with a pyrin, AIM, ASC, and death domain-like (PAAD)/PYRIN/DAPIN
      domain. CARDs regulate caspase family proteases. We show here that ASC binds by
      its CARD to procaspase-1 and to adapter proteins involved in caspase-1
      activation, thereby regulating cytokine pro-IL-1beta activation by this protease
      in THP-1 monocytes. ASC enhances IL-1beta secretion into the cell culture
      supernatants, at low concentrations, while suppressing at high concentrations.
      When expressed in HEK293 cells, ASC interferes with Cardiak/Rip2/Rick-mediated
      oligomerization of procaspase-1 and suppresses activation this protease, as
      measured by protease activity assays. Moreover, ASC also recruits procaspase-1
      into ASC-formed cytosolic specks, separating it from Cardiak. We also show that
      expression of the PAAD/PYRIN family proteins pyrin or cryopyrin/PYPAF1/NALP3
      individually inhibits IL-1beta secretion but that coexpression of ASC with these
      proteins results in enhanced IL-1beta secretion. However, expression of ASC
      uniformly interferes with caspase-1 activation and IL-1beta secretion induced by
      proinflammatory stimuli such as LPS and TNF, suggesting pathway competition.
      Moreover, LPS and TNF induce increases in ASC mRNA and protein expression in
      cells of myeloid/monocytic origin, revealing another level of cross-talk of
      cytokine-signaling pathways with the ASC-controlled pathway. Thus, our results
      suggest a complex interplay of the bipartite adapter protein ASC with PAAD/PYRIN
      family proteins, LPS (Toll family receptors), and TNF in the regulation of
      procaspase-1 activation, cytokine production, and control of inflammatory
      responses.

PMID- 14634132
TI  - Proinflammatory cytokines disrupt epithelial barrier function by apoptosis
      independent mechanisms.
AB  - It is well known that inflammatory conditions of the intestinal mucosa result in
      compromised barrier function. Inflammation is characterized by an influx into the
      mucosa of immune cells that influence epithelial function by releasing
      proinflammatory cytokines such as IFN-gamma and TNF-alpha. Mucosal barrier
      function is regulated by the epithelial apical junctional complex (AJC)
      consisting of the tight junction and the adherens junction. Since the AJC
      regulates barrier function, we analyzed the influence of IFN-gamma and TNF-alpha
      on its structure/function and determined the contribution of apoptosis to this
      process using a model intestinal epithelial cell line, T84, and IFN-gamma and TNF
      alpha. AJC structure/function was analyzed by confocal microscopy, biochemical
      analysis, and physiologic measurement of epithelial gate/fence function.
      Apoptosis was monitored by determining cytokeratin 18 cleavage and caspase-3
      activation. IFN-gamma induced time-dependent disruptions in epithelial gate
      function that were potentiated by coincubation with TNF-alpha. Tight junction
      fence function was somewhat disrupted. Cytokine treatment was associated with
      internalization of AJC transmembrane proteins, junction adhesion molecule 1,
      occludin, and claudin-1/4 with minimal effects on the cytoplasmic plaque protein
      zonula occludens 1. Detergent solubility profiles of junction adhesion molecule 1
      and E-cadherin and their affiliation with "raft-like" membrane microdomains were
      modified by these cytokines. Inhibition of cytokine-induced apoptosis did not
      block induced permeability defects; further emphasizing their primary influence
      on the epithelial AJC structure and barrier function. Our findings for the first
      time clearly separate the proapoptotic effects of IFN-gamma and TNF-alpha from
      their abilities to disrupt barrier function.

PMID- 14634133
TI  - Suppression of immune induction of collagen-induced arthritis in IL-17-deficient
      mice.
AB  - Interleukin-17 is a T cell-derived proinflammatory cytokine. This cytokine is
      suspected to be involved in the development of rheumatoid arthritis (RA) because
      this cytokine expression is augmented in synovial tissues of RA patients. The
      pathogenic roles of IL-17 in the development of RA, however, still remain to be
      elucidated. In this study, effects of IL-17 deficiency on collagen-induced
      arthritis (CIA) model were examined using IL-17-deficient mice (IL-17(-/-) mice).
      We found that CIA was markedly suppressed in IL-17(-/-) mice. IL-17 was
      responsible for the priming of collagen-specific T cells and collagen-specific
      IgG2a production. Thus, these observations suggest that IL-17 plays a crucial
      role in the development of CIA by activating autoantigen-specific cellular and
      humoral immune responses.

PMID- 14634134
TI  - Alterations in granule matrix and cell surface of focal adhesion kinase-deficient
      mast cells.
AB  - Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase that plays
      an important role in many cellular processes and is tyrosine phosphorylated after
      FcepsilonRI aggregation in mast cells. In mice, null mutation of the fak gene
      results in a lethal phenotype in which the embryos fail to develop past day 8.5
      of gestation. To study the role of FAK in these mast cells, 8.5-day embryos were
      isolated and placed in culture with IL-3 and stem cell factor (SCF). Although FAK
      was not required for the development of mast cells in culture, the FAK(-/-)
      embryo-derived mast cells had several distinct characteristics. Compared with the
      controls, the mast cells that lack FAK were less metachromatic and by electron
      microscopy had granules that appeared largely electron lucid, although their
      histamine content was unchanged. The FAK-deficient mast cells had a reduction in
      the content of chondroitin/dermatan sulfate, the major glycosaminoglycan
      component of the granular matrix. The FAK-deficient cells had fewer microvilli
      that were fused with each other, giving the cell surface a ruffled appearance.
      There was also a 3-fold increase in the number of cells highly expressing beta(7)
      integrin. However, signal transduction from the high affinity IgE receptor for
      the secretion of histamine was similar in the wild-type, heterozygote, and the
      FAK-deficient cells. The FcepsilonRI-induced tyrosine phosphorylation of
      paxillin, Crk-associated tyrosine kinase substrate (CAS), and mitogen-activated
      protein kinase proteins was independent of FAK. These results indicate that FAK
      plays a role in regulating the glycosaminoglycan content of the secretory
      granules and influences the cell surface morphology of mast cells.

PMID- 14634135
TI  - Toll-like receptor-2, but not Toll-like receptor-4, is essential for development
      of oviduct pathology in chlamydial genital tract infection.
AB  - The roles of Toll-like receptor (TLR) 2 and TLR4 in the host inflammatory
      response to infection caused by Chlamydia trachomatis have not been elucidated.
      We examined production of TNF-alpha and IL-6 in wild-type TLR2 knockout (KO), and
      TLR4 KO murine peritoneal macrophages infected with the mouse pneumonitis strain
      of C. trachomatis. Furthermore, we compared the outcomes of genital tract
      infection in control, TLR2 KO, and TLR4 KO mice. Macrophages lacking TLR2
      produced significantly less TNF-alpha and IL6 in response to active infection. In
      contrast, macrophages from TLR4 KO mice consistently produced higher TNF-alpha
      and IL-6 responses than those from normal mice on in vitro infection. Infected
      TLR2-deficient fibroblasts had less mRNA for IL-1, IL-6, and macrophage
      inflammatory protein-2, but TLR4-deficient cells had increased mRNA levels for
      these cytokines compared with controls, suggesting that ligation of TLR4 by whole
      chlamydiae may down-modulate signaling by other TLRs. In TLR2 KO mice, although
      the course of genital tract infection was not different from that of controls,
      significantly lower levels of TNF-alpha and macrophage-inflammatory protein-2
      were detected in genital tract secretions during the first week of infection, and
      there was a significant reduction in oviduct and mesosalpinx pathology at late
      time points. TLR4 KO mice responded to in vivo infection similarly to wild-type
      controls and developed similar pathology. TLR2 is an important mediator in the
      innate immune response to C. trachomatis infection and appears to play a role in
      both early production of inflammatory mediators and development of chronic
      inflammatory pathology.

PMID- 14634136
TI  - Aberrant inflammation and lethality to septic peritonitis in mice lacking STAT3
      in macrophages and neutrophils.
AB  - Stat3 is a transcription factor mediating anti-inflammatory properties of IL-10.
      In the present study, we demonstrate a pivotal role of Stat3 expressed in innate
      immune cells during septic peritonitis induced by cecal ligation and puncture
      (CLP). Mice with targeted disruption of Stat3 in macrophages and neutrophils were
      succumbed to septic peritonitis induced by CLP. The mice displayed an excessive
      local and systemic inflammation relative to the control mice, an event that was
      accompanied by substantial increases in the level of multiple cytokines. Hepatic
      and renal injury was significantly exacerbated in mice with Stat3 deficiency.
      Despite enhanced inflammatory responses, the mice failed to facilitate bacterial
      clearance as compared with the control mice. In addition, the mice exhibited an
      increased lethality after i.p. inoculation of live bacteria recovered from CLP
      mice. In vitro, resident peritoneal macrophages from mice with Stat3 deficiency
      impaired bactericidal activity relative to the control whereas productions of
      inflammatory cytokines were significantly augmented when cells were stimulated
      with a synthetic lipopeptide, macrophage-activating lipopeptide-2 and LPS.
      Elicited macrophages and neutrophils with Stat3 deficiency also impaired
      bactericidal activity as compared with those with Stat3. Lysosomal enzyme
      release, an effector molecule for bacterial clearance, was significantly
      decreased in elicited leukocytes with Stat3 deficiency while increasing the
      production of inflammatory cytokines. Altogether, these results suggest that
      macrophage/neutrophil-specific STAT3 is crucial in not only modulating multiple
      organ failure associated with systemic inflammation but also intensifying the
      bactericidal activity, which highlight the significance of cell-specific Stat3 in
      the protective immunity during sepsis.

PMID- 14634137
TI  - Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1
      phosphate receptor agonist FTY720.
AB  - The sphingosine 1-phosphate receptor agonist FTY720 is a novel immunomodulator
      that sequesters lymphocytes in secondary lymphoid organs and thereby prevents
      their migration to sites of inflammation. However, there is currently no
      information available on whether this drug affects Th1 or Th2 cell-mediated lung
      inflammatory responses. The effect of FTY720 was therefore investigated in a
      murine airway inflammation model using OVA-specific, in vitro differentiated, and
      adoptively transferred Th1 and Th2 cells. Both Th1 and Th2 cells express a
      similar pattern of FTY720-targeted sphingosine 1-phosphate receptors. The OVA
      induced Th1-mediated airway inflammation characterized by increased numbers of
      lymphocytes and neutrophils in bronchoalveolar lavage fluid was significantly
      inhibited by oral FTY720 treatment. Similarly, FTY720 suppressed the Th2 cell
      induced bronchoalveolar lavage fluid eosinophilia and the infiltration of T
      lymphocytes and eosinophils into the bronchial tissue. Moreover, the Ag-induced
      bronchial hyperresponsiveness to inhaled metacholine was almost completely
      blocked. The inhibitory effect of FTY720 on airway inflammation, induction of
      bronchial hyperresponsiveness, and goblet cell hyperplasia could be confirmed in
      an actively Ag-sensitized murine asthma model, clearly indicating that Th2 cell
      driven allergic diseases such as asthma could benefit from such treatment.

PMID- 14634138
TI  - Placental cell expression of HLA-G2 isoforms is limited to the invasive
      trophoblast phenotype.
AB  - The HLA-G message is alternatively spliced into multiple transcripts, two of
      which encode soluble isoforms. To initiate studies on the specific functions of
      the soluble isoforms, we produced soluble rHLA-G1 (rsG1) and rsG2 in human
      embryonic kidney 293 cells and characterized the proteins. Both isoforms were
      glycosylated and formed disulfide-bonded oligomers. Recombinant sG1 associated
      with beta(2)-microglobulin, whereas rsG2 did not. Mouse mAb generated to rsG1 (1
      2C3), which identified exclusively sG1, and mAb generated to rsG2 (26-2H11),
      which identified both soluble and membrane G2 (m/sG2), were used for
      immunohistochemical isoform mapping studies on placental tissue sections. Soluble
      G1 protein was abundant in many subpopulations of trophoblast cells, whereas
      m/sG2 protein was present exclusively in extravillous cytotrophoblast cells.
      Although both isolated placental villous cytotrophoblast cells and chorion
      membrane extravillous cytotrophoblast cells contained mRNAs encoding sG1 and sG2,
      protein expression was as predicted from the immunostains with m/sG2 present only
      in the invasive trophoblast subpopulation. Analysis of function by Northern and
      Western blotting demonstrated that both rsG1 and rsG2 inhibit CD8alpha expression
      on PBMC without changing CD3delta expression or causing apoptotic cell death.
      Collectively, the studies indicate that: 1) both sG1 and m/sG2 are produced in
      placentas; 2) transcription and translation are linked for sG1, but not G2; 3)
      expression of G2 is exclusively associated with the invasive phenotype; and 4)
      the two isoforms of sG may promote semiallogeneic pregnancy by reducing
      expression of CD8, a molecule required for functional activation of CTL.

PMID- 14634140
TI  - Mechanisms of spontaneous resolution versus fibrosis in granulomatous
      experimental autoimmune thyroiditis.
AB  - When granulomatous experimental autoimmune thyroiditis (G-EAT) was induced in
      CBA/J or DBA/1 mice, thyroid lesions resolved in less severe (3+) G-EAT in wild
      type mice or severe (5+) G-EAT in IFN-gamma(-/-) mice, but progressed to fibrosis
      in 5+ G-EAT in wild-type mice. To define the mechanisms leading to these distinct
      outcomes, the expression of inflammatory and apoptotic molecules and infiltrating
      cells was evaluated using immunohistochemistry, RT-PCR, and confocal microscopy.
      The ratio of CD4(+)/CD8(+) T cells in thyroid infiltrates was one factor that
      predicted G-EAT outcome. CD4(+) T cells outnumbered CD8(+) T cells when lesions
      progressed to fibrosis, while CD8(+) T cells outnumbered CD4(+) T cells in
      thyroids that resolved. Fas, Fas ligand, FLIP, TNF-alpha, inducible NO synthase,
      TGF-beta, and IFN-gamma were highly expressed by infiltrating cells when G-EAT
      progressed to fibrosis. The expression of active caspase-3 was low, possibly
      contributing to the persistence of CD4(+) T cells in fibrosis. In contrast, FLIP
      was mainly expressed by thyrocytes in resolving G-EAT, the expression of active
      caspase-3 was high, and resolution correlated with apoptosis of infiltrating
      cells. There was also relatively less expression of TGF-beta, IFN-gamma, TNF
      alpha, and inducible NO synthase and higher expression of IL-10 in resolving G
      EAT than in G-EAT that progressed to fibrosis. These differences were
      particularly striking when comparing IFN-gamma(-/-) vs wild-type mice. These
      results suggest that several opposing biological mechanisms contribute to the
      outcome of an ongoing autoimmune response. These include differential expression
      of pro- and antiapoptotic molecules, cytokines, and the ratio of CD4(+) vs CD8(+)
      T cells.

PMID- 14634139
TI  - B-1 B cells mediate required early T cell recruitment to elicit protein-induced
      delayed-type hypersensitivity.
AB  - We define the initiation of elicited delayed-type hypersensitivity (DTH) as a
      series of processes leading to local extravascular recruitment of effector T
      cells. Responses thus have two sequential phases: 1) 2-h peaking initiation
      required for subsequent recruitment of T cells, and 2) the late classical 24-h
      component mediated by the recruited T cells. We analyzed DTH initiation to
      protein Ags induced by intradermal immunization without adjuvants. Ag-spceific
      initiating cells are present by 1 day in spleen and lymph nodes. Their
      phenotypes, determined by depletion of cell transfers by mAb and complement, are
      CD5(+), CD19(+), CD22(+), B220(+), Thy1(+), and Mac1(+), suggesting that they are
      B-1 B cells. DTH initiation is absent in micro MT B cell and xid B-1 cell
      deficient mice, is impaired in mice unable to secrete IgM, and is reconstituted
      with 1 day immune serum, suggesting that early B-1 cell-derived IgM is
      responsible. Study of complement C5a receptor-deficient mice, anti-C5 mAb
      neutralization, or mast cell deficiency suggests that DTH initiation depends on
      complement and mast cells. ELISPOT assay confirmed production of Ag-specific IgM
      Abs at days 1 and 4 in wild-type mice, but not in B-1 cell-deficient xid mice. We
      conclude that rapidly activated B-1 cells produce specific IgM Abs which, after
      local secondary skin challenge, form Ag-Ab complexes that activate complement to
      generate C5a. This stimulates C5a receptors on mast cells to release vasoactive
      substances, leading to endothelial activation for the 2-h DTH-initiating
      response, allowing local recruitment of DTH-effector T cells.

PMID- 14634141
TI  - The plant lectin wheat germ agglutinin inhibits the binding of pemphigus
      foliaceus autoantibodies to desmoglein 1 in a majority of patients and prevents
      pathomechanisms of pemphigus foliaceus in vitro and in vivo.
AB  - Pemphigus foliaceus (PF) is a life-threatening autoimmune blistering skin disease
      caused by pathogenic IgG autoantibodies against desmoglein 1 (dg1), a desmosomal
      cadherin-type adhesion glycoprotein. Using lectins and glycosidases, we have
      shown that dg1 displays an N-glycosylation pattern of the complex triantennary
      type. We have found that lectins and glycosidases interfere with N-bound sugar
      residues on the amino-terminal ectodomain of dg1 and completely abolish, in
      vitro, the antigenicity of dg1 in most of the patients' sera. Moreover, in an ex
      vivo model using punch biopsies from normal human skin, we demonstrate that
      preincubation of the epidermis in wheat germ agglutinin (WGA) prevents PF
      autoantibody binding, acantholysis, and subcorneal blistering. In addition, we
      show that topical treatment with WGA inhibits PF autoantibody binding to
      keratinocytes in both newborn BALB/c mice and in organotypic human epidermis
      grafted onto the back of SCID mice. The epidermis of these pretreated animals
      displays a regular morphology, whereas control animals develop the
      immunopathologic phenotype of PF. These findings suggest that WGA may interfere
      with autoantibody binding to dg1, preventing experimental PF without affecting
      the adhesive function of dg1. Our observations may provide a new approach to the
      therapy of PF.

PMID- 14634142
TI  - Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus
      macaques.
AB  - The immune modulatory molecule CTLA-4 (CD152), through interactions with the B7
      costimulatory molecules, has been shown to be a negative regulator of T cell
      activation in various murine model systems. Abs that block CTLA-4 function can
      enhance immune responses that mediate potent antitumor activity. However, CTLA-4
      blockade can also exacerbate autoimmune disease. The safety and activity of anti
      CTLA-4 Abs in primates has not been addressed. To that end, we generated human
      Abs against CTLA-4 using transgenic mice expressing human Ig genes. A high
      affinity Ab (10D1) that blocked the binding of CTLA-4 to the B7-1 and B7-2
      ligands and had cross-reactivity with macaque CTLA-4 was chosen for further
      development. Administration of 10D1 to cynomolgus macaques significantly enhanced
      Ab responses to hepatitis surface Ag and a human melanoma cell vaccine. Anti-self
      Ab responses as measured by immunoassays using lysate from melanocyte-rich
      tissues were elicited in those animals receiving the melanoma cell vaccine and
      anti-CTLA-4 Ab. Remarkably, chronic administration of 10D1 did not result in
      measurable polyclonal T cell activation, significant alteration of the lymphocyte
      subsets, or induce clinically observable autoimmunity. Repeated dosing of the
      10D1 did not elicit monkey anti-human Ab responses in the monkeys. These
      observations support the development of CTLA-4 blockade for human immunotherapy.

PMID- 14634143
TI  - Chromatin specificity of anti-double-stranded DNA antibodies and a role for Arg
      residues in the third complementarity-determining region of the heavy chain.
AB  - A spontaneous, autoreactive autoantibody called SN5-18 (IgG2b, kappa) binds to a
      complex of H2A/H2B/dsDNA in chromatin, but erroneously appears to bind dsDNA when
      the Ab is used in a form that is not highly purified. Because of this finding, we
      evaluated the antigenic specificity of a prototypic anti-dsDNA Ab, 3H9/Vkappa4,
      now used widely in transgenic studies of tolerance and autoimmunity. We found
      that the purified mAb 3H9/Vkappa4 binds chromatin and specifically a complex of
      H2A/H2B/dsDNA, but not dsDNA in solid phase or in solution. When used in the form
      of culture supernatant or as a standard protein G preparation, mAb 3H9/Vkappa4
      appears to bind dsDNA, apparently due to nuclear proteins in the preparation that
      assemble on target DNA. Because of the reported role of V(H)CDR3 Arg residues in
      dsDNA binding and the near identity of the SN5-18 sequence to other dsDNA
      specific Ab, we tested the contributions of two V(H)CDR3 Arg residues in SN5-18
      to chromatin specificity. We found that both these Arg residues at positions 104
      and 106 were required for detectable chromatin binding. These results indicate a
      role for V(H)CDR3 Arg residues in chromatin specificity of lupus-derived
      autoantibodies. Further, they provide an explanation for a possible discrepancy
      in the form of tolerance observed in different anti-DNA Ig transgene models.

PMID- 14634144
TI  - Immune modulation in multiple sclerosis patients treated with the pregnancy
      hormone estriol.
AB  - The protective effect of pregnancy on putative Th1-mediated autoimmune diseases,
      such as multiple sclerosis and rheumatoid arthritis, is associated with a Th1 to
      Th2 immune shift during pregnancy. The hormone estriol increases during pregnancy
      and has been shown to ameliorate experimental autoimmune encephalomyelitis and
      collagen-induced arthritis. In addition, estrogens induce cytokine changes
      consistent with a Th1 to Th2 shift when administered in vitro to human immune
      cells and in vivo to mice. In a pilot trial, oral estriol treatment of relapsing
      remitting multiple sclerosis patients caused significant decreases in enhancing
      lesions on brain magnetic resonance imaging. Here, the immunomodulatory effects
      of oral estriol therapy were assessed. PBMCs collected longitudinally during the
      trial were stimulated with mitogens, recall Ags, and glatiramer acetate. Cytokine
      profiles of stimulated PBMCs were determined by intracellular cytokine staining
      (IL-5, IL-10, IL-12 p40, TNF-alpha, and IFN-gamma) and cytometric bead array (IL
      2, IL-4, IL-5, IL-10, TNF-alpha, and IFN-gamma). Significantly increased levels
      of IL-5 and IL-10 and decreased TNF-alpha were observed in stimulated PBMC
      isolated during estriol treatment. These changes in cytokines correlated with
      reductions of enhancing lesions on magnetic resonance imaging in relapsing
      remitting multiple sclerosis. The increase in IL-5 was primarily due to an
      increase in CD4(+) and CD8(+) T cells, the increase in IL-10 was primarily due to
      an increase in CD64(+) monocytes/macrophages with some effect in T cells, while
      the decrease in TNF-alpha was primarily due to a decrease in CD8(+) T cells.
      Further study of oral estriol therapy is warranted in Th1-mediated autoimmune
      diseases with known improvement during pregnancy.

PMID- 14634145
TI  - Injection of immature dendritic cells into adjuvant-treated skin obviates the
      need for ex vivo maturation.
AB  - A key and limiting step in the process of generating human monocyte-derived
      dendritic cells (DC) for clinical applications is maturation. In the setting of
      immunotherapy, DC are matured ex vivo by culturing them with various agents that
      mimic the conditions encountered at a site of inflammation. This study examined
      whether the ex vivo DC maturation step could be replaced by maturing DC in situ
      by injecting immature DC into sites pre-exposed to agents that induce a
      microenvironment conducive to in situ maturation of the injected DC. The
      hypothesis was that recapitulation of the physiological conditions occurring
      during pathogen infection would lead to optimal conditions for DC maturation,
      migration, and function. Murine immature DC injected into adjuvant (Adjuprime,
      poly-arginine, or Imiquimod)-pretreated skin exhibited lymph node migratory
      capacity comparable to and immunostimulatory capacity equal to or exceeding that
      of ex vivo matured DC. Acquisition of migratory capacity did not always correlate
      with enhanced immunostimulatory capacity. Immunostimulatory capacity was not
      enhanced when mature DC were injected into adjuvant-pretreated sites and remained
      below that seen with immature DC matured in situ. Immature DC injected into
      adjuvant-pretreated sites were more effective than mature DC in stimulating
      antitumor immunity in mice. (111)Indium-labeled human monocyte-derived immature
      DC injected into adjuvant (Imiquimod)-pretreated sites in cancer patients
      acquired lymph node migratory capacity comparable to ex vivo matured DC. This
      study shows that in situ maturation offers a simpler and potentially superior
      method to generate potent immunostimulatory DC for clinical immunotherapy.

PMID- 14634146
TI  - Identification of five new HLA-B*3501-restricted epitopes derived from common
      melanoma-associated antigens, spontaneously recognized by tumor-infiltrating
      lymphocytes.
AB  - We previously described HLA-B35-restricted melanoma tumor-infiltrating lymphocyte
      responses to frequently expressed melanoma-associated Ags: tyrosinase, Melan
      A/MART-1, gp100, MAGE-A3/MAGE-A6, and NY-ESO-1. Using clones derived from these
      TIL, we identified in this study the corresponding epitopes. We show that five of
      these epitopes are new and that melanoma cells naturally present all the six
      epitopes. Interestingly, five of these epitopes correspond to or encompass
      melanoma-associated Ag epitopes presented in other HLA contexts, such as A2, A1,
      B51, and Cw3. In particular, the HLA-B35-restricted Melan-A epitope is mimicked
      by the peptide 26-35, already known as the most immunodominant melanoma epitope
      in the HLA-A*0201 context. Because this peptide lacked adequate anchor amino acid
      residues for efficient binding to HLA-B35, modified peptides were designed. Two
      of these analogues were found to induce higher PBL- and tumor-infiltrating
      lymphocyte-specific responses than the parental peptide, suggesting that they
      could be more immunogenic in HLA-B*3501 melanoma patients. These data have
      important implications for the formulation of polypeptide-based vaccines as well
      as for the monitoring of melanoma-specific CTL response in HLA-B*3501 melanoma
      patients.

PMID- 14634147
TI  - Differential regulation of peripheral CD4+ T cell tolerance induced by deletion
      and TCR revision.
AB  - In Vbeta5 transgenic mice, mature Vbeta5(+)CD4(+) T cells are tolerized upon
      recognition of a self Ag, encoded by a defective endogenous retrovirus, whose
      expression is confined to the lymphoid periphery. Cells are driven by the
      tolerogen to enter one of two tolerance pathways, deletion or TCR revision.
      CD4(+) T cells entering the former pathway are rendered anergic and then
      eliminated. In contrast, TCR revision drives gene rearrangement at the endogenous
      TCR beta locus and results in the appearance of Vbeta5(-), endogenous Vbeta(+),
      CD4(+) T cells that are both self-tolerant and functional. An analysis of the
      molecules that influence each of these pathways was conducted to understand
      better the nature of the interactions that control tolerance induction in the
      lymphoid periphery. These studies reveal that deletion is efficient in
      reconstituted radiation chimeras and is B cell, CD28, inducible costimulatory
      molecule, Fas, CD4, and CD8 independent. In contrast, TCR revision is
      radiosensitive, B cell, CD28, and inducible costimulatory molecule dependent, Fas
      and CD4 influenced, and CD8 independent. Our data demonstrate the differential
      regulation of these two divergent tolerance pathways, despite the fact that they
      are both driven by the same tolerogen and restricted to mature CD4(+) T cells.

PMID- 14634148
TI  - Comparative genetic studies on the APRR5 and APRR7 genes belonging to the
      APRR1/TOC1 quintet implicated in circadian rhythm, control of flowering time, and
      early photomorphogenesis.
AB  - In Arabidopsis thaliana, a number of circadian-associated factors have been
      identified. Among those, TOC1 (TIMING OF CAB EXPRESSION 1) is believed to be a
      component of the central oscillator. TOC1 is a member of a small family of
      proteins, designated as Arabidopsis PSEUDO-RESPONSE REGULATORS (APRR1/TOC1,
      APRR3, APRR5, APRR7, and APRR9). Nonetheless, it is not very clear whether or not
      the APRR family members other than APRR1/TOC1 are also implicated in the
      mechanisms underlying the circadian rhythm. To address this issue further, here
      we characterized a set of T-DNA insertion mutants, each of which is assumed to
      have a severe lesion in each one of the quintet genes (i.e. APRR5 and APRR7). For
      each of these mutants (aprr5-11 and aprr7-11) we demonstrate that a given
      mutation singly, if not directly, affects the circadian-associated biological
      events simultaneously: (i) flowering time in the long-day photoperiod conditions,
      (ii) red light sensitivity of seedlings during the early photomorphogenesis, and
      (iii) the period of free-running rhythms of certain clock-controlled genes
      including CCA1 and APRR1/TOC1 in constant white light. These results suggest
      that, although the quintet members other than APRR1/TOC1 may not be directly
      integrated into the framework of the central oscillator, they are crucial for a
      better understanding of the molecular mechanisms underlying the Arabidopsis
      circadian clock.

PMID- 14634149
TI  - An Arabidopsis ACT2 dominant-negative mutation, which disturbs F-actin
      polymerization, reveals its distinctive function in root development.
AB  - Eight functional actin genes are present in Arabidopsis: The functional
      characterization of these genes in loss-of-function mutants is difficult, because
      highly conserved isovariants are generally expressed in the same tissue. We
      isolated a novel semi-dominant mutant allele (act2-2D) of an actin gene, ACT2,
      with a missense mutation which causes an amino acid substitution at the surface
      of the ACT2 protein. ACT2 promoter::ACT2-2D transgenic plants showed the same
      phenotype as act2-2D, indicating that act2-2D is a dominant-negative mutant. act2
      2D exhibited defects in the initiation and elongation of root hairs, the
      elongation of root epidermal cells, and growth in aerial portions. Specifically,
      radial cell expansion was reduced and occasional cell death occurred in
      trichoblasts but not in atrichoblasts of the root epidermis. In contrast, cell
      division patterns in the root meristem were not affected. act2-3, a loss-of
      function ACT2 mutant, did not develop most of these morphological abnormalities.
      Actin filament (F-actin) bundles in root epidermal cells of act2-2D were shorter
      than in the wild type and in the loss-of-function mutant. We conclude that
      defective F-actin polymerization caused the aberrant cell morphology in a
      dominant-negative manner, and that ACT2 functions in cell elongation and root
      hair formation.

PMID- 14634150
TI  - In the unicellular red alga Rhodella violacea iron deficiency induces an
      accumulation of uncoupled LHC.
AB  - Iron plays a key role in the synthesis and functioning of the photosynthetic
      apparatus. Conditions of partial iron deficiency that lead to a relatively stable
      phenotype were established and the effects of starvation studied in the
      unicellular red alga, Rhodella violacea. Synthesis of the photosynthetic pigments
      were found to decrease, with phycobiliproteins being affected to a lesser extent
      than chlorophyll a. Biophysical, biochemical and immunological approaches were
      used to show that the PSI content is highly diminished and the PSII/PSI
      stoichiometry increased by a factor of 5 compared to standard conditions.
      Meanwhile light-harvesting complex (LHC) was still assembled in the thylakoid
      membranes at unchanged levels. The use of translation inhibitors for either
      nuclear- or plastid-encoded polypeptides revealed that uncoupled LHC may be
      responsible for the high wavelength-fluorescence contribution observed around 700
      710 nm. There is no evidence for the synthesis of new chlorophyll-protein
      complexes.

PMID- 14634151
TI  - A putative plastidic glucose translocator is expressed in heterotrophic tissues
      that do not contain starch, during olive (Olea europea L.) fruit ripening.
AB  - Metabolite-specific transporters are present in the inner membrane of the plastid
      envelope allowing transport between the plastid and other cellular compartments.
      A plastidic glucose translocator (pGlcT) in leaf mesophyll cells transports
      glucose from chloroplast stroma to the cytosol after amylolytic starch
      degradation at night. Here we report the cloning of a pGlcT expressed in olive
      fruits (Olea europea L.). Our results showed high expression of pGlcT in non
      green heterotrophic fruit tissues. Expression of pGlcT in olive fruits was
      somewhat higher compared to leaves, and continued until the black, mature fruit
      stage. We cloned part of tomato pGlcT and found that it is also expressed
      throughout fruit development implying a role for pGlcT in heterotrophic tissues.
      Light and electron microscopic characterization of plastid structural changes
      during olive fruit ripening revealed the transition of chloroplast-like plastids
      into starchless, non-green plastids; in mature olive fruits only chromoplasts
      were present. Together, these findings suggest that olive pGlcT is abundant in
      chromoplasts during structural changes, and provide evidence that pGlcT may play
      different physiological roles in ripening fruits and possibly in other non
      photosynthetic organs.

PMID- 14634152
TI  - Purification and characterization of an antifungal chitinase in jelly fig (Ficus
      awkeotsang) achenes.
AB  - A method was developed to purify a 30-kDa protein from jelly fig (Ficus
      awkeotsang) pericarp, including preparation of jelly curd from achenes,
      extraction of proteins from the curd, and isolation of the 30-kDa protein by
      anion-exchanger and gel filtration. Chitinase activity was detected in the
      purified 30-kDa protein by activity staining in both non-denaturing gel
      electrophoresis and SDS-PAGE. Isoelectrofocusing showed that the isoelectric
      point of the 30-kDa protein was lower than pH 3.5. The K(m), k(cat), optimal pH
      and temperature of this putative chitinase were determined to be 0.076 mM, 0.089
      s(-1), pH 4, and 60 degrees C, respectively. The purified 30-kDa protein was
      thermostable (retaining activity up to 65 degrees C for several hours) and could
      be stored at 4 degrees C for a year without apparent loss of chitinase activity.
      Antifungal activity of this putative chitinase was measured in terms of
      inhibition of Colletotrichum gloeosporioides spore germination.

PMID- 14634153
TI  - A new 9-lipoxygenase cDNA from developing rice seeds.
AB  - We isolated a novel C9 position specific lipoxygenase (r9-LOX1) cDNA from
      developing rice seeds. The enzymatic features of r9-LOX1 resembled those of rice
      LOX-L3 known to be contained in rice germ and to have C9-specific LOX activity.
      However, the expression level of the r9-LOX1 gene was higher in imbibed seeds
      rather than developing seeds. A homology search against the rice nucleotide
      database revealed the r9-LOX1 gene to be on rice chromosome 3 (accession number
      AC093017). The restriction enzyme map of the reported genomic sequence agreed
      with the result of the Southern blot analysis for the r9-LOX1. The enzyme could
      be useful for in vitro synthesis of 9,10-ketol-octadecadienoic acid.

PMID- 14634154
TI  - Lotus japonicus: a new model to study root-parasitic nematodes.
AB  - Sedentary plant-parasitic nematodes engage in complex interactions, and induce
      specialized feeding structures by redirecting plant developmental pathways, and
      parallels have been observed with rhizobial nodule development on legumes. A
      model legume would greatly facilitate a better understanding of the differences
      between parasitic (nematode) and mutualistic (rhizobia and mycorrhizae)
      symbioses, and we have developed Lotus japonicus as such a model. Conditions for
      efficient parasitism by root-knot nematode (Meloidogyne spp.) of the widely used
      Lotus "Gifu" ecotype were established. Features of Lotus biology, such as thin
      and translucent roots, proved ideal for monitoring the progress of nematode
      infection both on live specimens and post-staining. We examined L. japonicus
      mutants with nodulation phenotypes. One, har1, which is a hypernodulated mutant
      defective in a CLAVATA1-like receptor kinase gene, was found to be hyperinfected
      by M. incognita. However, another hypernodulated Lotus mutant exhibited the same
      level of M. incognita infection as wild-type plants. We also established
      conditions for infection of Lotus by soybean cyst nematode (Heterodera glycines).
      In contrast to the response to root-knot nematode, the Gifu ecotype is resistant
      to H. glycines, and elicits a hypersensitive response. This pattern of resistance
      recapitulates that seen on nematode-resistant soybean plants. We conclude that L.
      japonicus is a powerful model legume for studying compatible and incompatible
      plant-nematode interactions.

PMID- 14634155
TI  - Evidence from engineering that decarboxylation of free serine is the major source
      of ethanolamine moieties in plants.
AB  - Plants form ethanolamine (Etn) moieties by decarboxylating serine or
      phosphatidylserine (PtdSer), and use them to make phosphatidylethanolamine,
      phosphatidylcholine, choline, and glycine betaine. Serine decarboxylation is
      mediated by a serine decarboxylase (SDC) that is unique to plants and has a
      characteristic N-terminal extension. This extension was shown to have little
      influence on function of the enzyme in vitro. To explore the importance of SDC
      and its extension in vivo, native or truncated versions of the Arabidopsis enzyme
      were expressed in tobacco. Transgene expression increased SDC activity by up to
      10-fold and free Etn level up to 6-fold, but did not change levels of serine,
      choline, phosphocholine, or phosphatidyl bases. The truncated enzyme gave
      significantly higher Etn levels. These results show that SDC activity exerts
      substantial control over flux to Etn, and suggest that the enzyme's N-terminus
      may have a regulatory role. In complementary studies with Arabidopsis, we showed
      that a mutant with 9-fold elevated mitochondrial PtdSer decarboxylase activity
      had normal pools of serine, Etn, and Etn metabolites. Taken together, these data
      indicate that serine decarboxylation is the main source of Etn moieties in
      plants. The ability to enhance serine --> Etn flux should advance engineering of
      choline and glycine betaine accumulation.

PMID- 14634156
TI  - Behavior of vacuoles during microspore and pollen development in Arabidopsis
      thaliana.
AB  - Using the cryo-fixation/freeze-substitution method, we studied the
      ultrastructural changes and behavior of vacuoles and related organelles (rER and
      Golgi bodies) during microspore and pollen development, and pollen maturation of
      Arabidopsis thaliana. In young microspores forming exine (pollen outer cell
      wall), vacuoles looked like those of somatic cells. In microspores during the
      formation of intine (inner cell wall), a large vacuole appeared which was made by
      fusion of pre-existing vacuoles and probably absorption of solutions. In the
      young pollen grain after the first mitosis, a large vacuole was divided into
      small vacuoles. The manner of division was not by binary fission and
      centripetally, but by the invagination of tonoplasts from one side to the
      opposite side of a vacuole. After the second mitosis, somatic type vacuoles
      disappeared. In mature pollen grains just before germination, membrane-bound
      structures containing fine fibrillar substances (MBFs) appeared. The MBFs were
      considered to be storage vacuoles. In pollen grains from flowers in bloom, MBFs
      changed to lysosomal structures with acid phosphatases (lytic vacuole). They
      gradually increased in number and volume, and decomposed the cytoplasm. The
      autolysis of pollen grains is the first finding in this study, which may
      contribute to the loss of ability of pollen germination after anthesis.

PMID- 14634157
TI  - Expression analyses of beta-tubulin isotype genes in rice.
AB  - Microtubules play important roles in many cellular processes, such as cell
      division and cell elongation in plants. beta-tubulins, which are the basic
      components of microtubules, are encoded by multigene family in eukaryotes and
      their nucleotide sequences are highly conserved in protein coding regions. A
      homology search within the rice expressed sequence tag database identified at
      least eight beta-tubulin (OsTUB) isotypes including three novel OsTUB genes.
      Northern analysis using specific probes to 3'-UTR of OsTUB isotypes showed
      differential and tissue-specific expression. Seven out of eight OsTUB genes
      dominantly expressed in leaf sheath, while OsTUB8 was preferentially expressed in
      anther including mature pollens. The existence of anther-specific beta-tubulin
      suggests its unique role in the formation of microtubules during the anther and
      pollen development or pollen tube growth. Furthermore, transcripts of OsTUB5, 6
      and 7 genes were significantly enhanced by gibberellin but all eight OsTUB genes
      were repressed by abscisic acid. Our results imply that OsTUB genes are
      differentially regulated by developmental and hormonal signals and different
      OsTUB isotypes might play special role in the growth and development of specific
      organs in rice.

PMID- 14634158
TI  - A member of the germin-like protein family is a highly conserved mycorrhiza
      specific induced gene.
AB  - A Medicago truncatula cDNA encoding a germin-like protein (GLP) was isolated from
      a suppression subtractive hybridization cDNA library enriched for arbuscular
      mycorrhiza (AM)-induced genes. The MtGLP1 amino acid sequence shows some striking
      differences to previously described plant GLP sequences and might therefore
      represent a new subgroup of this multigene family. The MtGlp1 mRNA was strongly
      induced in roots and root cultures colonized by the AM fungus Glomus
      intraradices. Whereas MtGlp1 is strongly induced in AM, no transcripts of the
      gene were detected in non-infected roots or in roots after infection with the
      oomycete root pathogen Aphanomyces euteiches or with Rhizobia. Increased
      phosphate levels during fertilization also could not stimulate MtGlp1
      transcription. Hence, MtGlp1 induction seems to be an AM-specific phenomenon. In
      situ hybridization showed that MtGlp1 is localized in arbuscule containing cells.
      A putative orthologue of this AM-specific GLP gene could be localized in a second
      legume Lotus japonicus, indicating that the regulation of a member of the GLP
      family belongs to a conserved mechanism in AM regulation in different plant
      species.

PMID- 14634159
TI  - Studies on mechano-perception in the Characeae: transduction of pressure signals
      into electrical signals.
AB  - Mechano-perception by Chara cells was studied with an emphasis on the role of the
      nodal complex in transducing pressure signals into electrical signals. Three
      types of experimental material were used: (1) tandem internodal cells connected
      by a single layer of nodal cells; (2) single internodal cells, from which either
      apical or basal nodes were removed by ligation and cutting; (3) single internodes
      from which both nodes had been removed. Exposure to a hypertonic solution
      (sorbitol or sucrose) induced a depolarization at the node in 1 and 2.
      Depolarization did not occur at the ligated end of the cell in 2, or at all in 3.
      Addition of K+ increased the magnitude of the response, whilst it was
      significantly decreased by the divalent cations, Ca2+ and Mg2+. Electrical
      resistance decreased at the node during the depolarization, showing that a
      passive diffusion potential was responsible. I suggest that the change in the
      trans-nodal hydraulic pressure difference mechanically stretches the plasma
      membrane, and this induces the electrical depolarization.

PMID- 14634160
TI  - Synthesis of a callosic substance during rhizoid differentiation in Spirogyra.
AB  - Spirogyra living in running water is anchored to the substratum by rhizoids that
      form at the ends of the filaments. A new terminal cell differentiates into a
      rhizoid cell if the filament is injured. The mode of growth changes from diffuse
      to tip growth when rhizoid differentiation begins. In this study, we found that a
      callosic substance was synthesized during rhizoid differentiation. Decreasing the
      cell turgor, lowering extracellular Ca2+ or adding Gd3+, all inhibited the
      commencement of rhizoid differentiation as well as synthesis of the callose-like
      substance at the tip of the terminal cell. A callosic substance was also
      synthesized during formation of the conjugation tube.

PMID- 14634161
TI  - The evolutionarily conserved OsPRR quintet: rice pseudo-response regulators
      implicated in circadian rhythm.
AB  - In Arabidopsis thaliana, a number of circadian-associated factors have been
      identified, including TOC1 (TIMING OF CAB EXPRESSION 1) that is believed to be a
      component of the central oscillator. TOC1 is a member of a small family of
      proteins, designated as ARABIDOPSIS PSEUDO-RESPONSE REGULATORS (APRR1/TOC1,
      APRR3, APRR5, APRR7, and APRR9). As demonstrated previously, these APRR1/TOC1
      quintet members are crucial for a better understanding of the molecular links
      between circadian rhythms, control of flowering time through photoperiodic
      pathways, and also photosensory signal transduction in this dicotyledonous plant.
      In this respect, both the dicotyledonous (e.g. A. thaliana) and monocotyledonous
      (e.g. Oryza sativa) plants might share the evolutionarily conserved molecular
      mechanism underlying the circadian rhythm. Based on such an assumption, and as
      the main objective of this study, we asked the question of whether rice also has
      a set of pseudo-response regulators, and if so, whether or not they are
      associated with the circadian rhythm. Here we showed that rice has five members
      of the OsPRR family (Oryza sativa Pseudo-Response Regulator), and also that the
      expressions of these OsPRR genes are under the control of circadian rhythm. They
      are expressed in a diurnal and sequential manner in the order of OsPRR73
      (OsPRR37)-->OsPRR95 (OsPRR59)-->OsPRR1, which is reminiscent of the circadian
      waves of the APRR1/TOC1 quintet in A. thaliana. These and other results of this
      study suggested that the OsPRR quintet, including the ortholog of APRR1/TOC1,
      might play important roles within, or close to, the circadian clock of rice.

PMID- 14634162
TI  - Characterization of the APRR9 pseudo-response regulator belonging to the
      APRR1/TOC1 quintet in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana, a number of circadian-associated factors have been
      identified, including TOC1 (TIMING OF CAB EXPRESSION1) that is believed to be a
      component of the central oscillator. TOC1 is a member of a small family of
      proteins, designated as ARABIDOPSIS PSEUDO-RESPONSE REGULATORS (APRR1/TOC1,
      APRR3, APRR5, APRR7, and APRR9). As demonstrated previously, these APRR1/TOC1
      quintet members are crucial for a better understanding of the molecular links
      between circadian rhythms and photosensory signal transduction. Here we focused
      on the light-induced quintet member, APRR9, and three critical issues with regard
      to this member were simultaneously addressed: (i) clarification of the mechanism
      underlying the light-dependent acute response of APRR9, (ii) clarification of the
      phenotype of a null mutant of APRR9, (iii) identification of protein(s) that
      interacts with APRR9. In this study, we present the results that support the
      following views. (i) A phytochrome-mediated signaling pathway(s) activates the
      transcription of APRR9, leading to the acute light response of APRR9. (ii) The
      severe mutational lesion of APRR9 singly, if not directly, affects the period
      (and/or phase) of free-running rhythms, in continuous light, of every circadian
      controlled gene tested, including the clock genes, APRR1/TOC1, CCA1, and LHY.
      (iii) The APRR9 protein is capable of interacting with APRR1/TOC1, suggesting a
      hetrodimer formation between these cognate family members. These results are
      discussed within the context of a current consistent model of the Arabidopsis
      circadian oscillator.

PMID- 14634163
TI  - Expression profiles of Arabidopsis phospholipase A IIA gene in response to biotic
      and abiotic stresses.
AB  - We examined the transcripts that showed changes among the ca.7,000 Arabidopsis
      full-length cDNAs under biotic and abiotic stresses. Expression of Arabidopsis
      phospholipase A IIA (AtPLA IIA) gene was induced by various treatments such as
      pathogen inoculation (Alternaria alternata, Alternaria brassicicola and
      Colletotrichum higginsianum), cold, high-salinity, abscisic acid, salicylic acid,
      methyl jasmonate, ethephon, paraquat, rose bengal, UV-C and CuSO(4)-treatments.
      The regulation of AtPLA IIA gene expression under biotic and abiotic stresses was
      analyzed with AtPLA IIA promoter region (from +95 to -1,405) fused to the GUS
      reporter gene. In conclusion, the promoter activity is induced under these
      stresses.

PMID- 14634164
TI  - Angle's classification--time to move on?

PMID- 14634165
TI  - TP MOrth Cases Prize 2002.

PMID- 14634166
TI  - Orthodontic and orthognathic management of a patient with osteogenesis imperfecta
      and dentinogenesis imperfecta: a case report.
AB  - This case report describes a patient's severe Class III malocclusion, managed
      with a combination of orthodontic and orthognathic treatment. The medical history
      was complicated by osteogenesis imperfecta and dentinogenesis imperfecta. In
      addition the patient was a Jehovah's Witness. Patients with osteogenesis
      imperfecta carry an increased risk of perioperative haemorrhage, and this led to
      bimaxillary surgery being carried out as two discrete surgical episodes for the
      patient described. In addition, the risk of enamel fracture led to orthodontic
      bands being cemented on all teeth. In spite of the increased risks a successful
      outcome was achieved.

PMID- 14634168
TI  - Effect of inbreeding and endogamy on occlusal traits in human isolates.
AB  - OBJECTIVE: To discuss the genetic basis of occlusal traits through analysis of
      the effects of inbreeding in a subdivided isolated community. SUBJECTS AND
      METHODS: The sample comprised dental casts of 224 children, aged 7-14 years, from
      15 villages of the Island of Hvar, Croatia. MAIN OUTCOME MEASURES: Studied traits
      were Angle class, overjet, vertical bite, overbite, and crowding/spacing. DESIGN:
      Children with complete grandparental endogamy (all four grandparents born in the
      village of residence of the examinee) were compared to children with incomplete
      grandparental endogamy. In addition, children resident in the group of villages
      with a high prevalence of inbreeding were compared to children resident in the
      groups of villages with moderate and low prevalence of inbreeding. RESULTS: In
      both designs, inbreeding seemed to increase the mean values of overjet, overbite,
      and vertical bite, while it had little or no effect on crowding/spacing. Angle
      classes were correlated to inbreeding at the individual level, but this was not
      supported at the population level. The effects were stronger in the subsample
      with bilaterally concordant Angle classes. CONCLUSION: The observed inbreeding
      effects imply that the genetic basis of some occlusal traits is polygenic and, in
      considerable part, influenced by rare and recessive genetic variants.

PMID- 14634169
TI  - Clinical trials in orthodontics II: assessment of the quality of reporting of
      clinical trials published in three orthodontic journals between 1989 and 1998.
AB  - AIMS: To test the hypothesis that the quality of reporting of orthodontic
      clinical trials is insufficient to allow readers to assess the validity of the
      trial. DESIGN: A retrospective observational study. SETTING: The American Journal
      of Orthodontics and Dentofacial Orthopedics (AJODO), the British Journal of
      Orthodontics (BJO) and European Journal of Orthodontics (EJO). DATA SOURCE:
      Clinical trials published between 1989 and 1998. METHOD: A hand search was
      performed to identify all clinical trials. The concealment of allocation, whether
      the trial was randomized, double blind, and whether there was a description of
      withdrawals and dropouts was recorded. RESULTS: One hundred and fifty-five trial
      reports were identified of which 4 (2.6%) were adequately concealed, 85 (54.8%)
      were described as being randomized, 10 (6.5%) as double-blind, and 44 (28.4%)
      gave a description of withdrawals and drop-outs from the trial. The type of
      randomization was considered appropriate in 78 (50.3%) reports and in 57 (36.8%)
      reports the level of blinding was considered appropriate. When assessed for the
      risk of bias in the reported trials,(1) one trial (0.6%) had a low risk of bias,
      17 (11%) a moderate risk, and 137 (88.4%) a high risk. CONCLUSIONS: In general
      the quality of reporting orthodontic clinical trials was insufficient to allow
      readers to assess the validity of the trials. Reporting of clinical trials could
      be improved by orthodontic journals adopting the CONSORT statement(2,)(3) to
      ensure that all relevant information is provided.

PMID- 14634170
TI  - Fluoridated elastomers: in vivo versus in vitro fluoride release.
AB  - OBJECTIVES: To compare (i) the in vivo release of fluoride from fluoridated
      elastomers to the in vitro release, and (ii) the residual fluoride content of the
      elastomers after 1 week in the mouth with and without fluoride toothpaste and
      mouthrinse. DESIGN: A prospective, longitudinal, cross-over study. SUBJECTS AND
      METHOD: Six subjects were recruited by poster to take part in the study. Each
      subject had one premolar in each quadrant to which a bracket could be fixed and
      exemplary oral hygiene. Elastomers were then placed on these brackets.
      INTERVENTION: The study was divided into two parts: (i) subjects used oral
      hygiene products with fluoride and (ii) oral hygiene products with fluoride were
      excluded. Both groups of elastomers were left in the mouth for 1 week. After
      collection the elastomers were stored in distilled water. MAIN OUTCOME MEASURES:
      The amount of residual fluoride in the ligatures after they have been placed in
      the mouth for 1 week was compared with the cumulative fluoride release in vitro
      over 1 week and 6 months. RESULTS: Only 13 per cent of the total amount of
      fluoride in fluoridated elastomers was released during the first week in vitro,
      compared with 90 per cent in vivo. There was a significantly greater amount (P =
      0.001) of residual fluoride when the elastomers were in the mouth for 1 week in
      the presence of fluoride toothpaste and mouthrinse, than when fluoride
      supplements were excluded. CONCLUSIONS: (1) Higher levels of fluoride are lost
      from the fluoride elastomers in vivo than in vitro during the first week. (2) A
      significantly greater amount of residual fluoride was released from the
      elastomers placed in the mouth when fluoride toothpaste and mouthrinse were used.

PMID- 14634171
TI  - Effect of fluoride exposure on cariostatic potential of orthodontic bonding
      agents: an in vitro evaluation.
AB  - AIMS: The aims of this in vitro study were to compare the cariostatic potential
      of a resin modified glass ionomer cement (Fuji Ortho LC) to that of a resin
      control (Transbond) for bracket bonding and to compare the effect of extrinsic
      fluoride application on the cariostatic potential of each material. SETTING: Ex
      vivo study. MATERIALS AND METHODS: Orthodontic brackets were bonded to 40
      extracted premolars, 20 with Fuji Ortho LC and 20 with Transbond. The teeth were
      subjected to pH cycling, pH 4.55, and pH 6.8, over a 30-day period. Ten teeth
      bonded with each material were immersed in a 1000 ppm fluoride solution for 2
      minutes each day. Fluoride release was measured throughout the study from all
      teeth. After 30 days, the teeth were assessed visually for signs of enamel
      decalcification. RESULTS: Significant differences in decalcification existed
      macroscopically between all four groups of teeth, with the exception of those
      bonded with Fuji Ortho LC alone compared with Transbond alone (P = 0.22), and
      Fuji Ortho LC alone compared with Transbond with added fluoride (P = 0.3).
      Fluoride release from Fuji Ortho LC alone fell to minimal values, but with the
      addition of extrinsic fluoride the levels fell initially and then followed an
      upward trend. There was minimal fluoride release, from Transbond alone, but with
      daily addition of extrinsic fluoride, subsequent fluoride release was increased.
      Significant differences existed in the amount of fluoride released between all
      groups, except comparing Fuji Ortho LC alone and Transbond with added fluoride.
      CONCLUSIONS: The results of this study have indicated that with an in vitro tooth
      bracket model, the creation of white spot inhibition could best be achieved by
      the use of a resin-modified glass ionomer cement, supplemented with fluoride
      exposure. The least protection was afforded by the composite control. The resin
      modified glass ionomer cement alone and the composite with added fluoride
      demonstrated equivalent protection.

PMID- 14634172
TI  - A clinical comparison of two chemically-cured adhesives used for indirect
      bonding.
AB  - OBJECTIVE: To compare and evaluate the clinical failure rates of the chemically
      cured composite bonding resins Sondhi Rapid Set (SD) and Maximum Cure (MC) when
      used in an indirect bonding technique. SETTING: In vivo study in the private
      orthodontic practice of a solo practitioner. MATERIALS AND METHODS: Forty
      consecutive patients meeting the inclusion criteria were assigned to alternating
      groups in a split-mouth study design. Group 1 had the maxillary right and
      mandibular left quadrants indirectly bonded using SD adhesive, while the
      contralateral quadrants were bonded using MC adhesive. Group 2 had the opposite
      sides bonded to Group 1. One patient was lost from each group. Over a 6-month
      observation period, all loose brackets were recorded and the data compared with a
      Wilcoxon sign-rank test. RESULTS: Of the 363 brackets placed in each group, 36
      with the SD adhesive came loose (9.9 per cent failure rate) compared with five
      from the MC group (1.4 per cent failure rate, P = 0.0001). In the maxillary arch,
      seven brackets from the SD quadrants came loose versus one for the MC (P =
      0.109). In the mandibular arch 29 brackets from the SD quadrants came loose
      during the 6-month observation period compared with four from the MC quadrants (P
      = 0.001). CONCLUSIONS: Both chemically-cured adhesives (SD and MC) examined in
      this study were suitable for the indirect bonding of brackets. The SD adhesive
      had seven times the number of breakages than the MC adhesive in both arches (P =
      0.0001).

PMID- 14634173
TI  - How to ... do a randomized controlled trial.

PMID- 14634176
TI  - Invisalign: early experiences.
AB  - This article describes the Invisalign technique. It is based on the author's
      personal experience of over 60 cases started in the private practice setting. The
      technology behind Invisalign and its development is reviewed. The Invisalign
      clinical technique is described, and the advantages and disadvantages of using
      Invisalign are highlighted.

PMID- 14634177
TI  - Aesthetic horizontal reference line.

PMID- 14634179
TI  - Workplace counselling.

PMID- 14634181
TI  - Urine mutagenicity and lymphocyte DNA damage in fruit growers occupationally
      exposed to the fungicide captan.
AB  - AIMS: To determine haematological parameters, urine mutagenicity (on three
      Salmonella typhimurium strains), and DNA damage (using the comet assay) in
      mononuclear leucocytes of farmers before and after a one-day spraying period of
      pear and apple trees with the fungicide captan in usual conditions. METHODS:
      Fruit growers were exposed to captan during the 1998 (n = 12) and/or the 2000
      spraying seasons (n = 17). Biological samples were collected on the morning of
      the day of spraying (S1), the evening after spraying (S2), and the morning of the
      day after (S3). The UK Predictive Operator Exposure Model (UK-POEM) was used to
      quantify pesticide exposure intensity. RESULTS: No effect was observed on
      haematological parameters for these two spraying seasons. Proportions of
      mutagenic urine samples did not significantly differ between S1 and S2/S3
      sampling points. In contrast with strains TA97a and YG1041 mainly sensitive to
      frameshift mutations, a positive trend was observed between the difference (S3
      S1) of mutagenic power on strain TA102 detecting base-pair mutations and the
      exposure predicted value given by UK-POEM, mainly due to parameters related to
      protective clothing. No significant variations in DNA damage levels were observed
      between S1 and S3, nor were correlations observed with parameters of pesticide
      exposure. CONCLUSIONS: A one-day spraying period with captan and other pesticides
      does not significantly induce DNA damages in mononuclear leucocytes. In contrast,
      an inefficient protective clothing could correlate with an increase in urine
      mutagenicity as assessed by the TA102 tester strain.

PMID- 14634180
TI  - Parental occupation at periconception: findings from the United Kingdom Childhood
      Cancer Study.
AB  - AIMS: To study the risk of childhood cancer in relation to parental occupation
      and related exposures. METHODS: Self reported occupational data from mothers and
      fathers of 3838 children with cancer and 7629 control children were analysed.
      Odds ratios were calculated for 31 "occupational groups" by parent, diagnostic
      group (leukaemia, acute lymphoblastic leukaemia (ALL), central nervous system
      tumours, and other cancers) and time of exposure (periconception, birth, and
      diagnosis). RESULTS: Findings did not support the hypothesis that occupational
      exposure of fathers to ionising radiation increases the risk of childhood cancer
      in their offspring. Specific examination of periconceptual chemical exposures
      showed small but statistically significant increased risks for leukaemia and ALL
      among children whose fathers were exposed to exhaust fumes, driving, and/or
      inhaled particulate hydrocarbons. In the remaining analyses, a fourfold increase
      in the risk of other cancers was observed among the children of fathers working
      with leather but based on small numbers. Both maternal and paternal exposure to
      textile dust was related to an increased risk of other cancers. CONCLUSION:
      Results failed to produce any strong evidence to link parental occupational
      exposures with an increased risk of childhood cancer. No relation was found for
      paternal periconceptual exposure to ionising radiation. The consistency of the
      associations observed between childhood leukaemia and paternal occupational
      exposure to exhaust fumes, driving, and/or inhaled particulate hydrocarbons at
      periconception suggest a small risk for vehicle related exhaust. However, other
      explanations cannot be excluded and further research into the nature of the
      associations is required.

PMID- 14634182
TI  - Mortality and cancer morbidity in a cohort of Canadian petroleum workers.
AB  - AIMS: To assess mortality and cancer morbidity in Canadian petroleum workers and
      explore exposure-response relations for specific petroleum agents. METHODS: A
      total of 25 292 employees hired between 1964 and 1994 were linked to the Canadian
      tumour registry and national mortality database. Exposure-response trends were
      assessed for hydrocarbon solvents/fuels, hydrocarbon lubricants, petroleum
      coke/spent catalyst, and hydrogen sulphide (H2S). RESULTS: External comparison
      analyses (mortality and incidence) showed deficits for all causes and all
      malignant neoplasms combined and were consistent with expectation for most
      malignant and non-malignant sites analysed. Gall bladder cancer mortality was
      increased among males based on four deaths, but cases had no common job
      assignments and the increase was focused in workers employed <10 years.
      Mesothelioma incidence was increased. Most exposure-specific analyses were
      compromised by small numbers. Statistically significant increases were observed
      for H2S exposure and a subgroup of accidental deaths as well as for petroleum
      coke/spent catalyst exposure and lung cancer. While both findings have a degree
      of biologic plausibility, the H2S association, which exhibited a clearer exposure
      response pattern, could be subject to unmeasured confounders. Additionally,
      interpretation was complicated by the high correlation between hydrocarbon and
      H2S exposures. With regard to lung cancer, the analysis could not adequately
      control for smoking, was based on small numbers, and exhibited a tenuous exposure
      response pattern. CONCLUSION: The findings for mesothelioma suggest the need for
      continued attention to asbestos in the petroleum industry. The relation between
      accidental deaths and H2S exposure deserves closer scrutiny in similarly exposed
      populations. Further analyses of lung cancer are underway and will be reported
      separately.

PMID- 14634183
TI  - Prevalence of respiratory symptoms among female flight attendants and teachers.
AB  - BACKGROUND: Potential health effects of the indoor environment in office
      buildings and aircraft have generated considerable concern in recent years. AIMS:
      To analyse the prevalence of self reported respiratory symptoms and illnesses in
      flight attendants (FAs) and schoolteachers. METHODS: Data were collected as part
      of a study of reproductive health among female FAs. The prevalences of work
      related eye, nose, and throat symptoms, wheezing, physician diagnosed asthma,
      chest illness, and cold or flu were calculated and stratified by smoking status
      in 1824 FAs and 331 schoolteachers. RESULTS: FAs and teachers were significantly
      more likely to report work related eye (12.4% and 7.4 %, respectively), nose
      (15.7% and 8.1%), and throat symptoms (7.5% and 5.7%) than were other working
      women (2.9% eye, 2.7% nose, and 1.3% throat symptoms). FAs were significantly
      more likely than teachers and referent working women to report chest illness
      during the prior three years (32.9%, 19.3%, 7.2%, respectively). Both study
      groups were more likely to report five or more episodes of cold or flu in the
      past year than were other working women (10.2% of FAs, 8.2% of teachers, 2.3% of
      referents), and both groups were more likely to report wheezing than other
      working women (22.8% of FAs, 28.4% of teachers, 16.4% of referents). FAs were
      significantly less likely than teachers and other working women to report ever
      having been diagnosed with asthma (8.2%, 13.3%, 11.8%, respectively).
      CONCLUSIONS: Overall, FAs and schoolteachers report a higher prevalence of work
      related upper respiratory symptoms, chest illness, and cold or flu than the
      general working population.

PMID- 14634185
TI  - Respiratory symptoms and cotton dust exposure; results of a 15 year follow up
      observation.
AB  - AIMS: To determine chronic effects of long term exposure to cotton dust and
      endotoxin on incidence of respiratory symptoms and the effect of cessation of
      exposure. METHODS: Respiratory health in 429 Chinese cotton textile workers
      (study group) and 449 silk textile workers (control group) was followed
      prospectively from 1981 to 1996. Byssinosis, chest tightness, and non-specific
      respiratory symptoms were assessed by means of identical standardised
      questionnaires at four time points. Exposures to cotton dust and endotoxin were
      estimated using area samples collected at each survey. Incidence and persistence
      of symptoms were examined in relation to cumulative exposure and exposure
      cessation using generalised estimating equations (GEE). RESULTS: Among cotton
      workers, the cumulative incidence of byssinosis and chest tightness was 24% and
      23%, respectively, and was significantly more common in smokers than in non
      smokers. A high proportion of symptoms was found to be intermittent, rather than
      persistent. Among silk workers, no typical byssinosis was identified; the
      incidence of chest tightness was 10%. Chronic bronchitis, cough, and dyspnoea
      were more common and persistent in the cotton group than in the silk group.
      Significantly lower odds ratios for symptoms were observed in cotton workers who
      left the cotton mills; risk was also related to years since last worked.
      Multivariate analysis indicated a trend for higher cumulative exposure to
      endotoxin in relation to a higher risk for byssinosis. CONCLUSION: Chronic
      exposure to cotton dust is related to both work specific and non-specific
      respiratory symptoms. Byssinosis is more strongly associated with exposure to
      endotoxin than to dust. Cessation of exposure may improve the respiratory health
      of cotton textile workers; the improvement appears to increase with time since
      last exposure.

PMID- 14634186
TI  - Effects of measurement strategy and statistical analysis on dose-response
      relations between physical workload and low back pain.
AB  - BACKGROUND: In epidemiological studies on physical workloads and back complaints,
      among the important features in modelling dose-response relations are the
      measurement strategy of the exposure and the nature of the dose-response relation
      that is assumed. AIM: To evaluate the effect of these two features on the
      strength of the dose-response relation between physical load and severe low back
      pain. METHODS: The study population consisted of 769 workers in nursing homes and
      homes for the elderly. Observations at the workplace were made of 212 subjects.
      These observations were analysed to determine exposure to physical load according
      to two measurement strategies: the individual approach and the group approach.
      The nature of the dose-response relation was evaluated with nested logistic
      regression models. RESULTS: The group approach resulted in higher odds ratios for
      the associations between physical load and low back pain than the individual
      approach. Spline logistic regression models appeared to describe the dose
      response relation between physical load and low back pain best. The corresponding
      curve showed small changes in risk for small changes in exposure, whereas the
      categorical model only showed sudden large changes in risk at predefined exposure
      values. CONCLUSION: The choice for a particular measurement strategy of physical
      load influences the strength of the associations between physical load and severe
      low back pain. Spline models allow changes in risk over the whole exposure range
      and are therefore a promising approach to identify quantitative dose-response
      patterns between physical load and low back pain.

PMID- 14634187
TI  - From insecure to secure employment: changes in work, health, health related
      behaviours, and sickness absence.
AB  - AIMS: To determine whether change in employment status (from fixed term to
      permanent employment) is followed by changes in work, health, health related
      behaviours, and sickness absence. METHODS: Prospective cohort study with four
      year follow up. Data from 4851 (710 male, 4141 female) hospital employees having
      a fixed term or permanent job contract on entry to the study were collected at
      baseline and follow up. RESULTS: At baseline, compared to permanent employees,
      fixed term employees reported lower levels of workload, job security, and job
      satisfaction. They also reported greater work ability. All fixed term employees
      had a lower rate of medically certified sickness absence at baseline. Baseline
      rate ratios for those who remained fixed term were 0.64 (95% CI 0.55 to 0.75),
      and were 0.50 (95% CI 0.34 to 0.75) for those who later became permanent.
      Continuous fixed term employment was not associated with changes in the outcome
      measures. Change from fixed term to permanent employment was followed by an
      increase in job security, enduring job satisfaction, and increased medically
      certified sickness absence (compared to permanent workers rate ratio 0.96 (95% CI
      0.80 to 1.16)). Other indicators of work, health, and health related behaviours
      remained unchanged. CONCLUSION: Receiving a permanent job contract after fixed
      term employment is associated with favourable changes in job security and job
      satisfaction. The corresponding increase in sickness absence might be due to a
      reduction in presenteeism and the wearing off of health related selection.

PMID- 14634188
TI  - Occupational contact dermatitis to nickel: experience of the British
      dermatologists (EPIDERM) and occupational physicians (OPRA) surveillance schemes.
AB  - AIMS: To examine, from occupational surveillance reporting data, whether scheme
      reporters considered nickel exposure to play a role in occupational contact
      dermatitis (OCD) in the UK. METHODS: Data on occupational skin disease in the UK
      are collected by two occupational disease surveillance schemes, EPIDERM and OPRA.
      Cases of OCD believed to have relevant nickel exposure reported to EPIDERM or
      OPRA from February 1993 to January 1999 were studied. RESULTS: An estimate of
      1190 cases of occupational contact dermatitis thought to have relevant nickel
      exposure (12% of total estimated OCD) was derived from reports by dermatologists,
      an average of 198 per year. The highest incidence rates were seen in hairdressers
      (23.9/100 000 workers/year), bar staff (4.7), chefs and cooks (4.4), retail cash
      and checkout operators (2.8), and catering assistants (2.5). From May 1994 to
      January 1999, 158 cases of nickel associated dermatitis (1.9% of total OCD cases)
      were estimated; the most frequently reported occupations were electronic
      assemblers, nurses, sales assistants, and general assemblers. From July 1997 to
      January 1999, 547 positive patch tests to nickel were reported; in 195 cases
      (36%), nickel was felt to be a relevant occupational allergen (for example, coin
      handling). In hairdressers, nurses, cooks, and beauticians, nickel was usually
      considered, if relevant at all, to be only one of several causes of dermatitis.
      CONCLUSIONS: Up to 12% of total estimated cases of OCD were thought to be due in
      part to nickel. Results suggest that nickel hypersensitivity is one of several
      contributors to OCD in subjects with multiple occupational exposures. Coin
      handling may be a source of OCD to nickel.

PMID- 14634189
TI  - Occupational exposure of midwives to nitrous oxide on delivery suites.
AB  - AIMS: To compare environmental and biological monitoring of midwives for nitrous
      oxide in a delivery suite environment. METHODS: Environmental samples were taken
      over a period of four hours using passive diffusion tubes. Urine measurements
      were taken at the start of the shift and after four hours. RESULTS: Environmental
      levels exceeded the legal occupational exposure standards for nitrous oxide (100
      ppm over an 8 hour time weighted average) in 35 of 46 midwife shifts monitored.
      There was a high correlation between personal environmental concentrations and
      biological uptake of nitrous oxide for those midwives with no body burden of
      nitrous oxide at the start of a shift, but not for others. CONCLUSIONS: Greater
      engineering control measures are needed to reduce daily exposure to midwives to
      below the occupational exposure standard. Further investigation of the
      toxicokinetics of nitrous oxide is needed.

PMID- 14634190
TI  - Skin temperature recovery from cold provocation in workers exposed to vibration:
      a longitudinal study.
AB  - BACKGROUND: Vibration white finger (VWF) is characterised by arterial
      hyperresponsiveness and vasoconstriction following cold provocation. Several
      years after of removal from exposure, most subjects show improved finger systolic
      blood pressure (FSBP) under conditions of cold challenge, but continue to report
      cold hands and finger blanching. AIMS: To assess the underlying reasons for the
      persistence of cold symptoms. METHODS: A total of 204 former users of pneumatic
      tools with cold related hand symptoms were evaluated and then re-evaluated a year
      later. Symptoms were evaluated using the Stockholm Workshop Scale. Finger
      systolic blood pressure per cent (FSBP%) was assessed by comparing digital blood
      pressure in a cold provoked and normalised state. Fingertip skin temperature was
      measured during cooling and occlusion and during rewarming and recovery. RESULTS:
      There were dramatic improvements in FSBP% (14.3 mm Hg %), modest improvement in
      recovered skin temperature (0.86 degrees C), and no change in symptom stage. When
      the most symptomatic subjects (n = 75) were compared with the less symptomatic
      subjects (n = 129), there were similar inter-test improvements in FSBP%. Skin
      temperature recovery improved in the less symptomatic (+1.49 degrees C), but did
      not change in the most symptomatic group (-0.12 degrees C). However, the more
      symptomatic group had higher temperatures at the initial test, thus qualifying
      the result. CONCLUSIONS: Skin temperature recovery after cold challenge in
      subjects with VWF remains reduced in the symptomatic subjects several years after
      exposure removal. This is evident even when blood pressure has increased in the
      setting of cold provocation. Results suggest that in VWF, the dermal circulation
      remains impaired, even after the restoration of arterial blood pressure in the
      digits.

PMID- 14634191
TI  - Benzene and naphthalene in air and breath as indicators of exposure to jet fuel.
AB  - AIMS: To estimate exposures to benzene and naphthalene among military personnel
      working with jet fuel (JP-8) and to determine whether naphthalene might serve as
      a surrogate for JP-8 in studies of health effects. METHODS: Benzene and
      naphthalene were measured in air and breath of 326 personnel in the US Air Force,
      who had been assigned a priori into low, moderate, and high exposure categories
      for JP-8. RESULTS: Median air concentrations for persons in the low, moderate,
      and high exposure categories were 3.1, 7.4, and 252 microg benzene/m3 air, 4.6,
      9.0, and 11.4 microg benzene/m3 breath, 1.9, 10.3, and 485 microg naphthalene/m3
      air, and 0.73, 0.93, and 1.83 microg naphthalene/m3 breath, respectively. In the
      moderate and high exposure categories, 5% and 15% of the benzene air
      concentrations, respectively, were above the 2002 threshold limit value (TLV) of
      1.6 mg/m3. Multiple regression analyses of air and breath levels revealed
      prominent background sources of benzene exposure, including cigarette smoke.
      However, naphthalene exposure was not unduly influenced by sources other than JP
      8. Among heavily exposed workers, dermal contact with JP-8 contributed to air and
      breath concentrations along with several physical and environmental factors.
      CONCLUSIONS: Personnel having regular contact with JP-8 are occasionally exposed
      to benzene at levels above the current TLV. Among heavily exposed workers, uptake
      of JP-8 components occurs via both inhalation and dermal contact. Naphthalene in
      air and breath can serve as useful measures of exposure to JP-8 and uptake of
      fuel components in the body.

PMID- 14634192
TI  - Investigating the dose-response relation between air pollution and total
      mortality in the APHEA-2 multicity project.
AB  - BACKGROUND: Several recent studies have reported significant health effects of
      air pollution even at low levels of air pollutants, but in most of these studies
      linear non-threshold relations were assumed. AIMS: To investigate the NO2
      mortality dose-response association in nine cities participating in the APHEA-2
      project using two different methods: the meta-smooth and the cubic spline method.
      METHODS: The meta-smooth method developed by Schwartz and Zanobetti is based on
      combining individual city non-parametric smooth curves; the cubic spline method
      developed within the APHEA-2 project combines individual city estimates of cubic
      spline shaped dose-response relations. The meta-smooth method is easier and
      faster to implement, but the cubic spline method is more flexible for further
      investigation of possible heterogeneity in the dose-response curves among cities.
      RESULTS: In the range of the pollutant common to all cities the two methods gave
      similar and comparable curves. Using the cubic spline method it was found that
      smoking prevalence acts as an effect modifier with larger NO2 effects on
      mortality at lower smoking prevalence. CONCLUSIONS: The NO2-mortality association
      in the cities included in the present analysis, could be adequately estimated
      using the linear model. However, investigation of the city specific dose-response
      curves should precede the application of linear models.

PMID- 14634193
TI  - Increased occupational physical activity does not improve physical fitness.
AB  - AIM: To determine the possible influence of high physical load in the workplace
      on the physical fitness of employees. METHODS: The subjects (494 men) were tested
      by means of Baecke's questionnaire for evaluation of the Work Index, measuring
      occupational physical load. The EUROFIT battery of tests was used for testing the
      functional and motor abilities of the subjects. RESULTS: Subjects with a higher
      Work Index (n = 274) performed worse than the subjects with a lower Work Index (n
      = 220), indicating that high physical load in the workplace does not necessarily
      mean improvement in functional and motor abilities. The "heavy" workers were only
      found to have a stronger handgrip. This could be attributed to the fact that
      physical activity performed at the workplace did not have adequate intensity,
      volume, and duration to effect positive changes in other motor and functional
      capacities.

PMID- 14634194
TI  - Potential effects on human health of an ammonia rich atmospheric environment in
      an archaeologically important cave in southeast Asia.
AB  - This important cave is described together with an analysis of the potential
      health effects for humans inhabiting an ecosystem, albeit on a temporary basis,
      possessing an ammonia rich atmospheric environment. The work emphasises potential
      environmental hazards together with an evaluation of the range of clinical
      effects. The environmental pollution in this cave is generally unlikely to have
      marked adverse effects on temporary visitors who lack pre-existing respiratory
      impairments. It is suggested that ancient humans would, to avoid an unpleasant
      polluted environment, have confined most of their activities to the outer regions
      of the cave. Comparisons are made with other ammonia contaminated environments.

PMID- 14634195
TI  - World at work: hazards and controls in aluminium potrooms.

PMID- 14634196
TI  - The amount of sleep obtained by locomotive engineers: effects of break duration
      and time of break onset.
AB  - AIMS: To determine the effects of break duration and time of break onset on the
      amount of sleep that locomotive engineers obtain between consecutive work
      periods. METHODS: A total of 253 locomotive engineers (249 male, 4 female, mean
      age 39.7 years) participated. Data were collected at 14 rail depots, where
      participants drove electric or diesel locomotives; worked with another engineer
      or drove alone; carried passengers, freight, or coal; and operated in rural or
      urban areas. Participants completed sleep diaries and work diaries for a two week
      period while working their normal roster patterns. RESULTS: For breaks that began
      at similar times of day, total sleep time (TST) increased with break duration.
      For breaks of similar duration, TST was greater for those that occurred during
      the night-time than for those that occurred during the daytime. An average of 3.1
      7.9 hours sleep was obtained in 12 hour breaks (minimum break requirement in the
      Australian rail industry), depending on when the break began. CONCLUSIONS: The
      duration and timing of breaks are both important factors in determining the
      amount of sleep that locomotive engineers obtain between consecutive work
      periods. Consequently, minimum length break requirements that do not include a
      time of day component may not provide locomotive engineers with the opportunity
      to obtain a sufficient amount of sleep prior to resuming work.

PMID- 14634197
TI  - Under-ascertainment of multiple myeloma among participants in UK atmospheric
      atomic and nuclear weapons tests.
AB  - An inter-comparison of cases of multiple myeloma among UK participants in the
      UK's atmospheric atomic and nuclear weapons tests ascertained by direct follow up
      methods detected at least a third more cases than a strategy relying solely on
      data linkage between the Office of National Statistics and the Service Records
      Offices. These finding have implications for the conduct and robustness of follow
      up studies of long term health effects among participants in nuclear weapons
      tests.

PMID- 14634198
TI  - Effects of high-intensity intermittent training on potassium kinetics and
      performance in human skeletal muscle.
AB  - A rise in extracellular potassium concentration in human skeletal muscle may play
      an important role in development of fatigue during intense exercise. The aim of
      the present study was to examine the effect of intense intermittent training on
      muscle interstitial potassium kinetics and its relationship to the density of
      Na(+),K(+)-ATPase subunits and K(ATP) channels, as well as exercise performance,
      in human skeletal muscle. Six male subjects performed intense one-legged knee
      extensor training for 7 weeks. On separate days the trained leg (TL) and the
      control leg (CL) performed a 30 min exercise period of 30 W and an incremental
      test to exhaustion. At frequent intervals during the exercise periods
      interstitial potassium ([K(+)](I)) was determined by microdialysis, femoral
      arterial and venous blood samples were drawn and thigh blood flow was measured.
      Time to fatigue for TL was 28% longer (P < 0.05) than for CL (10.6 +/- 0.7 (mean
      +/-s.e.m.) versus 8.2 +/- 0.7 min). The amounts of Na(+),K(+)-ATPase alpha(1) and
      alpha(2) subunits were, respectively, 29.0 +/- 8.4 and 15.1 +/- 2.7% higher (P <
      0.05) in TL than in CL, while the amounts of beta(1) subunits and ATP-dependent
      K(+) (K(ATP)) channels were the same. In CL [K(+)](I) increased more rapidly and
      was higher (P < 0.05) throughout the 30 W exercise bout, as well at 60 and 70 W,
      compared to TL, whereas [K(+)](I) was similar at the point of fatigue (9.9 +/-
      0.7 and 9.1 +/- 0.5 mmol l(-1), respectively). During the 30 W exercise bouts and
      at 70 W during the incremental exercise femoral venous potassium concentration
      ([K(+)](v)) was higher (P < 0.05) in CL than in TL, but identical at exhaustion
      (6.2 +/- 0.2 mmol l(-1)). Release of potassium to the blood was not different in
      the two legs. The present data demonstrated that intense intermittent training
      reduce accumulation of potassium in human skeletal muscle interstitium during
      exercise, probably through a larger re-uptake of potassium due to greater
      activity of the muscle Na(+),K(+)-ATPase pumps. The lower accumulation of
      potassium in muscle interstitium in the trained leg was associated with delayed
      fatigue during intense exercise, supporting the hypothesis that interstitial
      potassium accumulation is involved in the development of fatigue.

PMID- 14634199
TI  - Neonatal maternal separation and sex-specific plasticity of the hypoxic
      ventilatory response in awake rat.
AB  - We tested the hypothesis that neonatal maternal separation (NMS), a form of
      stress that affects hypothalamo-pituitary-adrenal axis (HPA) function in adult
      rats, alters development of the respiratory control system. Pups subjected to NMS
      were placed in a temperature and humidity controlled incubator 3 h per day for 10
      consecutive days (P3 to P12). Control pups were undisturbed. Once they reached
      adulthood (8-10 weeks old), rats were placed in a plethysmography chamber for
      measurement of ventilatory and cardiovascular parameters under normoxic and
      hypoxic conditions. Measurement of c-fos mRNA expression in the paraventricular
      nucleus of the hypothalamus (PVH) combined with plasma ACTH and corticosterone
      levels confirmed that NMS effectively disrupted HPA axis function in males. In
      males, baseline minute ventilation was not affected by NMS. In contrast, NMS
      females show a greater resting minute ventilation due to a larger tidal volume.
      The hypoxic ventilatory response of male NMS rats was 25% greater than controls,
      owing mainly to an increase in tidal volume response. This augmentation of the
      hypoxic ventilatory response was sex-specific also because NMS females show an
      attenuated minute ventilation increase. Baseline mean arterial blood pressure of
      male NMS rats was 20% higher than controls. NMS-related hypertension was not
      significant in females. The mechanisms underlying sex-specific disruption of
      cardio-respiratory control in NMS rats are unknown but may be a consequence of
      the neuroendocrine disruption associated with NMS. These data indicate that
      exposure to a non-respiratory stress during early life elicits significant
      plasticity of these homeostatic functions which persists until adulthood.

PMID- 14634200
TI  - In vivo temporal and spatial distribution of depolarization and repolarization
      and the illusive murine T wave.
AB  - This study assessed in vivo temporal and spatial electrophysiological properties
      of murine hearts and the effect of manipulation of transmural action potential
      durations (APDs) on T wave morphology. Monophasic action potentials (MAPs) were
      acquired from multiple left ventricular sites. All MAPs exhibited a plateau
      phase, with a spike and dome appearance being present in epicardial recordings.
      Activation occurred from endocardial apex to epicardial apex and apex to base
      while repolarization occurred from base (shortest 90 eta0 level of repolarization
      (MAP90), 95.4 +/- 8.9 ms) to apex and epicardium to endocardium (longest MAP90,
      110.77 +/- 10.6 ms). The peak of phase 0 of the epicardial base MAP correlated
      with the return to baseline of the initial and usually dominant waveform of the
      QRS and the onset of the second usually smaller wave, which clearly occurred in
      early repolarization, thus establishing where depolarization ended and
      repolarization began on the murine ECG. This second waveform was similar to the J
      wave seen in larger animals. Despite temporal and spatial electrophysiological
      similarities, a T wave is frequently not seen on a murine ECG. There are several
      determinants of T wave morphology, including transmural activation time, slope of
      phase 3 repolarization and differences in epicardial, endocardial and M cell
      APDs. Experimental manipulation of murine transmural gradients by shortening
      epicardial MAP(90) to 84% of endocardial MAP90 the epicardial/endocardial ratio
      in larger mammals when a positive T wave is present, resulted in a positive
      murine T wave. Thus, manipulation of the transmural gradients such that they are
      similar to larger mammals can result in T waves with similar morphology.

PMID- 14634201
TI  - Activation of bronchopulmonary vagal afferent nerves with bradykinin, acid and
      vanilloid receptor agonists in wild-type and TRPV1-/- mice.
AB  - The vanilloid receptor TRPV1 (formerly VR1) has been implicated in the activation
      of nociceptive sensory nerves by capsaicin, noxious heat, protons, bradykinin,
      cannabinoids such as anandamide, and certain metabolites of arachidonic acid.
      Using TRPV1 knockout mouse (TRPV1-/-) we address the question of whether TRPV1 is
      obligatory for action potential discharge in vagal C-fibre terminals evoked by
      capsaicin, anandamide, acid and bradykinin. The response of a defined subtype of
      the vagal afferent bronchopulmonary C-fibres (conduction velocity < 0.7 ms(-1))
      to the putative TRPV1 activators was studied in vitro in the mouse
      isolated/perfused lung-nerve preparation. Capsaicin (1 microm) evoked action
      potential discharge of approximately 90% (28/31) of C-fibres in the TRPV1+/+
      mice, but failed to activate bronchopulmonary C-fibres in TRPV1-/- animals (n =
      10). Anandamide (3-100 microm) induced concentration-dependent activation of
      capsaicin-sensitive TRPV1+/+ C-fibres with a threshold of 3-10 microm, but failed
      to evoke substantive discharge in TRPV1-/- C-fibres. In the TRPV1+/+ mice, the B2
      receptor-mediated activation by bradykinin (1 microm) was restricted to the
      capsaicin-sensitive C-fibres. Bradykinin was effective in evoking B2 receptor
      mediated action potential discharge in TRPV1-/- C-fibres, but the response was
      significantly (P < 0.05) less persistent than in TRPV1+/+ C-fibres. Exposing the
      tissue to acid (pH = 5) excited both TRPV1+/+ and TRPV1-/- C-fibres. We conclude
      that TRPV1 is obligatory for vagal C-fibre activation by capsaicin and
      anandamide. By contrast, whereas TRPV1 may have a modulatory role in bradykinin
      and acid-induced activation of bronchopulmonary C-fibres, it is not required for
      action potential discharge evoked by these stimuli.

PMID- 14634202
TI  - Effects of acute and chronic endurance exercise on mitochondrial uncoupling in
      human skeletal muscle.
AB  - Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide
      translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of
      oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after
      prolonged exercise and/or endurance training, resulting in increased uncoupled
      respiration (UCR). Subjects were investigated with muscle biopsies before and
      after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance
      training. Mitochondria were isolated and respiration measured in the absence (UCR
      or state 4) and presence of ADP (coupled respiration or state 3). Protein
      expression of UCP3 and ANT was measured with Western blotting. After endurance
      training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT
      increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3
      remained unchanged. When expressed per unit of CS (a marker of mitochondrial
      volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43%
      after acute exercise and remained elevated after 3 h of recovery (P < 0.05),
      whereas the other muscle parameters remained unchanged. An intriguing finding was
      that acute exercise reversibly enhanced the capacity of mitochondria to
      accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In
      conclusion, UCP3 protein and UCR decrease after endurance training when related
      to mitochondrial volume. These changes may prevent excessive basal thermogenesis.
      Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not
      influence UCR or protein expression of UCP3 and ANT. The increased Ca2+
      resistance may prevent mitochondrial degradation and the mechanism needs to be
      further explored.

PMID- 14634203
TI  - Differential regulation of the slow and rapid components of guinea-pig cardiac
      delayed rectifier K+ channels by hypoxia.
AB  - The aim of this study was to examine the effects of acute hypoxia on the slow
      (I(Ks)) and rapid (I(Kr)) components of the native delayed rectifier K+ channel
      in the absence and presence of the beta-adrenergic receptor agonist isoproterenol
      (isoprenaline; Iso) using the whole-cell configuration of the patch-clamp
      technique. Hypoxia reversibly inhibited basal I(Ks). The effect could be mimicked
      by exposing the cells to the thiol-specific reducing agent dithiothreitol (DTT)
      and attenuated upon exposure of cells to the membrane-impermeant thiol-specific
      oxidizing compound 5,5'-dithio-bis[2-nitrobenzoic acid] (DTNB). In the presence
      of hypoxia, the K(0.5) for activation of I(Ks) by Iso was significantly decreased
      from 18.3 to 1.9 nm. DTT mimicked the effect of hypoxia on the sensitivity of
      I(Ks) to Iso while DTNB had no effect. Hypoxia increased the sensitivity of I(Ks)
      to histamine and forskolin suggesting that the effect of hypoxia is not occurring
      at the beta-adrenergic receptor. The increase in sensitivity of I(Ks) to Iso
      could be attenuated with addition of PKCbeta peptide to the pipette solution.
      While hypoxia and DTT inhibited basal I(Ks) they were without effect on I(Kr.) In
      addition, Iso did not appear to alter the magnitude of I(Kr) in the absence or
      presence of hypoxia. These data suggest that hypoxia regulates native I(Ks)
      through two distinct mechanisms: direct inhibition of basal I(Ks) and an increase
      in sensitivity to Iso that occurs downstream from the beta-adrenergic receptor.
      Both mechanisms appear to involve redox modification of thiol groups. In contrast
      native I(Kr) does not appear to be regulated by Iso, hypoxia or redox state.

PMID- 14634204
TI  - Repetitive firing of rat cerebellar parallel fibres after a single stimulation.
AB  - The excitatory postsynaptic currents (EPSCs) evoked in Purkinje cells (PCs) by
      stimulating parallel fibres (PFs) usually show a single peak, but EPSCs with
      multiple peaks (polyphasic EPSCs) can be observed in slices from animals older
      than 15 days. The EPSCs remain polyphasic when the postsynaptic current is
      reduced (either by reducing the intensity of the PF stimulation or by adding AMPA
      receptor antagonists) and when the PC membrane potential is made positive. Thus
      the late peaks are not due to postsynaptic active currents generated in the
      imperfectly clamped PC, and must arise from repetitive action potentials in the
      PF. Extracellular recordings from granule cell (GC) somata showed that a single
      PF stimulation can elicit a doublet or a train of action potentials. Both the
      late action potentials recorded in the GCs and the late peaks of the polyphasic
      EPSCs recorded in the PCs were reduced or abolished by paired-pulse stimulation
      of the PF or by bath application of the GABA(A) agonist muscimol. The late action
      potentials in the GCs were also suppressed by local application of muscimol
      around the cell body. We propose that after a single stimulation of a PF, the
      antidromic invasion of the ascending axon and the granule cell can trigger a
      doublet or a burst of action potentials which back-propagate into the PF (except
      for the first, which finds the PF still in its refractory period). The repetitive
      activation of the PF by a single stimulation could play a role in the induction
      of long-term depression.

PMID- 14634205
TI  - Functional markers and the "homogeneity" of human mesenchymal stem cells.

PMID- 14634206
TI  - Turning immunological memory into amnesia by depletion of dividing T cells.
AB  - Immunological memory, defined as more efficient immune responses on antigen
      reexposure, can last for decades. The current paradigm is that memory is
      maintained by antigen-experienced "memory T cells" that can be long-lived
      quiescent or dividing. The contribution of T cell division to memory maintenance
      is poorly known and has important clinical implications. In this study, we
      directly addressed the role of dividing T cells in immunological memory
      maintenance by evaluating the consequences of their elimination. The specific
      ablation of dividing T cells was obtained by administration of ganciclovir to
      immune mice expressing the herpes simplex type 1 thymidine kinase suicide gene in
      T cells. We show that depletion of dividing T cells for 5 or 2 weeks suffices to
      abolish in vitro and in vivo memory responses against the male H-Y
      transplantation alloantigen or against lymphocytic choriomeningitis virus
      antigens, respectively. Similar results were obtained after the nonspecific
      elimination of all dividing cells by using hydroxyurea, a cytostatic toxic agent
      commonly used for cancer chemotherapy. This immune amnesia occurred in otherwise
      immunocompetent mice and despite the persistence of functional quiescent T cells
      displaying a "memory" phenotype. Thus, division of antigen-experienced T cells is
      an absolute requirement for immunological memory maintenance and the current
      concept of memory T cells is challenged.

PMID- 14634207
TI  - TRF3, a TATA-box-binding protein-related factor, is vertebrate-specific and
      widely expressed.
AB  - TATA-box-binding protein (TBP) is a highly conserved RNA polymerase II general
      transcription factor that binds to the core promoter and initiates assembly of
      the preinitiation complex. Two proteins with high homology to TBP have been
      found: TBP-related factor 1 (TRF1), described only in Drosophila melanogaster,
      and TRF2, which is broadly distributed in metazoans. Here, we report the
      identification and characterization of an additional TBP-related factor, TRF3.
      TRF3 is virtually identical to TBP in the C-terminal core domain, including all
      residues involved in DNA binding and interaction with other general transcription
      factors. Like other TBP family members, the N-terminal region of TRF3 is
      divergent. The TRF3 gene is present and expressed in vertebrates, from fish
      through humans, but absent from the genomes of the urochordate Ciona intestinalis
      and the lower eukaryotes D. melanogaster and Caenorhabditis elegans. TRF3 is a
      nuclear protein that is present in all human and mouse tissues and cell lines
      examined. Despite the highly homologous TBP-like C-terminal core domain, gel
      filtration analysis indicates that the native molecular weight of TRF3 is
      substantially less than that of TFIID. Interestingly, after mitosis, reimport of
      TRF3 into the nucleus occurs subsequent to TBP and other basal transcription
      factors. In summary, TRF3 is a highly conserved vertebrate-specific TRF whose
      phylogenetic conservation, expression pattern, and other properties are distinct
      from those of TBP and all other TRFs.

PMID- 14634208
TI  - TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in
      [Ca2+]i.
AB  - Transient receptor potential (TRP) proteins are a diverse family of proteins with
      structural features typical of ion channels. TRPM5, a member of the TRPM
      subfamily, plays an important role in taste receptors, although its activation
      mechanism remains controversial and its function in signal transduction is
      unknown. Here we characterize the functional properties of heterologously
      expressed human TRPM5 in HEK-293 cells. TRPM5 displays characteristics of a
      calcium-activated, nonselective cation channel with a unitary conductance of 25
      pS. TRPM5 is a monovalent-specific, nonselective cation channel that carries Na+,
      K+, and Cs+ ions equally well, but not Ca2+ ions. It is directly activated by
      [Ca2+]i at concentrations of 0.3-1 microM, whereas higher concentrations are
      inhibitory, resulting in a bell-shaped dose-response curve. It activates and
      deactivates rapidly even during sustained elevations in [Ca2+]i, thereby inducing
      a transient membrane depolarization. TRPM5 does not simply mirror levels of
      [Ca2+]i, but instead responds to the rate of change in [Ca2+]i in that it
      requires rapid changes in [Ca2+]i to generate significant whole-cell currents,
      whereas slow elevations in [Ca2+]i to equivalent levels are ineffective.
      Moreover, we demonstrate that TRPM5 is not limited to taste signal transduction,
      because we detect the presence of TRPM5 in a variety of tissues and we identify
      endogenous TRPM5-like currents in a pancreatic beta cell line. TRPM5 can be
      activated physiologically by inositol 1,4,5-trisphosphate-producing receptor
      agonists, and it may therefore couple intracellular Ca2+ release to electrical
      activity and subsequent cellular responses.

PMID- 14634209
TI  - Frap, FKBP12 rapamycin-associated protein, is a candidate gene for the
      plasmacytoma resistance locus Pctr2 and can act as a tumor suppressor gene.
AB  - Susceptibility to mouse plasmacytomagenesis is a complex genetic trait controlled
      by several Pctr loci (Pctr1, Pctr2, etc). Congenic strain analysis narrowed the
      genetic interval surrounding the Pctr2 locus, and genes identified in the
      interval were sequenced from susceptible BALB/c and resistant DBA/2 mice. Frap
      (FKBP12 rapamycin-associated protein, mTOR, RAFT) was the only gene differing in
      amino acid sequence between alleles that correlated with strain sensitivity to
      tumor development. The in vitro kinase activity of the BALB/c FRAP allele was
      lower than the DBA/2 allele; phosphorylation of p53 and PHAS1/4EBP1 (properties
      of heat and acid stability/eukaryotic initiation factor 4E-binding protein) and
      autophosphorylation of FRAP were less efficient with the BALB/c allele. FRAP also
      suppressed transformation of NIH 3T3 cells by ras, with DBA/2 FRAP being more
      efficient than BALB/c FRAP. Rapamycin, a specific inhibitor of FRAP, did not
      inhibit growth of plasmacytoma cell lines. These studies identify Frap as a
      candidate tumor suppressor gene, in contrast to many reports that have focused on
      its prooncogenic properties. Frap may be similar to Tgfb and E2f in exerting both
      positive and negative growth-regulatory signals, depending on the timing,
      pathway, or tumor system involved. The failure of rapamycin to inhibit plasma
      cell tumor growth suggests that FRAP antagonists may not be appropriate for the
      treatment of plasma cell tumors. Pctr2 joins Pctr1 in possessing alleles that
      modify susceptibility to plasmacytomagenesis by encoding differences in
      efficiency of function (efficiency alleles), rather than all-or-none, gain-of
      function, or loss-of-function alleles. By analogy, human cancer may also result
      from the combined effects of several inefficient alleles.

PMID- 14634210
TI  - DNA bending and unbending by MutS govern mismatch recognition and specificity.
AB  - DNA mismatch repair is central to the maintenance of genomic stability. It is
      initiated by the recognition of base-base mismatches and insertion/deletion loops
      by the family of MutS proteins. Subsequently, ATP induces a unique conformational
      change in the MutS-mismatch complex but not in the MutS-homoduplex complex that
      sets off the cascade of events that leads to repair. To gain insight into the
      mechanism by which MutS discriminates between mismatch and homoduplex DNA, we
      have examined the conformations of specific and nonspecific MutS-DNA complexes by
      using atomic force microscopy. Interestingly, MutS-DNA complexes exhibit a single
      population of conformations, in which the DNA is bent at homoduplex sites, but
      two populations of conformations, bent and unbent, at mismatch sites. These
      results suggest that the specific recognition complex is one in which the DNA is
      unbent. Combining our results with existing biochemical and crystallographic data
      leads us to propose that MutS: (i) binds to DNA nonspecifically and bends it in
      search of a mismatch; (ii) on specific recognition of a mismatch, undergoes a
      conformational change to an initial recognition complex in which the DNA is
      kinked, with interactions similar to those in the published crystal structures;
      and (iii) finally undergoes a further conformational change to the ultimate
      recognition complex in which the DNA is unbent. Our results provide a structural
      explanation for the long-standing question of how MutS achieves mismatch repair
      specificity.

PMID- 14634211
TI  - Hematopoietic progenitors express neural genes.
AB  - Bone marrow, or cells selected from bone marrow, were reported recently to give
      rise to cells with a neural phenotype after in vitro treatment with neural
      inducing factors or after delivery into the brain. However, we showed previously
      that untreated bone marrow cells express products of the neural myelin basic
      protein gene, and we demonstrate here that a subset of ex vivo bone marrow cells
      expresses the neurogenic transcription factor Pax-6 as well as neuronal genes
      encoding neurofilament H, NeuN (neuronal nuclear protein), HuC/HuD (Hu-antigen
      C/Hu-antigen D), and GAD65 (glutamic acid decarboxylase 65), as well as the
      oligodendroglial gene encoding CNPase (2',3' cyclic nucleotide 3'
      phosphohydrolase). In contrast, astroglial glial fibrillary acidic protein (GFAP)
      was not detected. These cells also were CD34+, a marker of hematopoietic stem
      cells. Cultures of these highly proliferative CD34+ cells, derived from adult
      mouse bone marrow, uniformly displayed a phenotype comparable with that of
      hematopoietic progenitor cells (CD45+, CD34+, Sca-1+, AA4.1+, cKit+, GATA-2+, and
      LMO-2+). The neuronal and oligodendroglial genes expressed in ex vivo bone marrow
      also were expressed in all cultured CD34+ cells, and GFAP was not observed. After
      CD34+ cell transplantation into adult brain, neuronal or oligodendroglial markers
      segregated into distinct nonoverlapping cell populations, whereas astroglial GFAP
      appeared, in the absence of other neural markers, in a separate set of implanted
      cells. Thus, neuronal and oligodendroglial gene products are present in a subset
      of bone marrow cells, and the expression of these genes can be regulated in
      brain. The fact that these CD34+ cells also express transcription factors (Rex-1
      and Oct-4) that are found in early development elicits the hypothesis that they
      may be pluripotent embryonic-like stem cells.

PMID- 14634212
TI  - The RNA polymerase III transcriptome revealed by genome-wide localization and
      activity-occupancy relationships.
AB  - RNA polymerase III (Pol III) transcribes small untranslated RNAs, such as tRNAs.
      To define the Pol III transcriptome in Saccharomyces cerevisiae, we performed
      genome-wide chromatin immunoprecipitation using subunits of Pol III, TFIIIB and
      TFIIIC. Virtually all of the predicted targets of Pol III, as well as several
      novel candidates, were occupied by Pol III machinery. Interestingly, TATA box
      binding protein occupancy was greater at Pol III targets than virtually all Pol
      II targets, and the highly occupied Pol II targets are generally strongly
      transcribed. The temporal relationships between factor occupancy and gene
      activity were then investigated at selected targets. Nutrient deprivation rapidly
      reduced both Pol III transcription and Pol III occupancy of both a tRNA gene and
      RPR1. In contrast, TFIIIB remained bound, suggesting that TFIIIB release is not a
      critical aspect of the onset of repression. Remarkably, TFIIIC occupancy
      increased dramatically during repression. Nutrient addition generally
      reestablished transcription and initial occupancy levels. Our results are
      consistent with active Pol III displacing TFIIIC, and with inactivation/release
      of Pol III enabling TFIIIC to bind, marking targets for later activation. These
      studies reveal new aspects of the kinetics, dynamics, and targets of the Pol III
      system.

PMID- 14634214
TI  - Basic principles of cancer cell culture.

PMID- 14634213
TI  - P53 hot-spot mutants are resistant to ubiquitin-independent degradation by
      increased binding to NAD(P)H:quinone oxidoreductase 1.
AB  - Proteasomal degradation of p53 is mediated by two alternative pathways that are
      either dependent or independent of both Mdm2 and ubiquitin. The ubiquitin
      independent pathway is regulated by NAD(P)H: quinone oxidoreductase 1 (NQO1) that
      stabilizes p53. The NQO1 inhibitor dicoumarol induces ubiquitin-independent p53
      degradation. We now show that, like dicoumarol, several other coumarin and
      flavone inhibitors of NQO1 activity, which compete with NAD(P)H for binding to
      NQO1, induced ubiquitin-independent p53 degradation and inhibited wild-type p53
      mediated apoptosis. Although wild-type p53 and several p53 mutants were sensitive
      to dicoumarol-induced degradation, the most frequent "hot-spot" p53 mutants in
      human cancer, R175H, R248H, and R273H, were resistant to dicoumarol-induced
      degradation, but remained sensitive to Mdm2-ubiquitin-mediated degradation. The
      two alternative pathways for p53 degradation thus have different p53 structural
      requirements. Further mutational analysis showed that arginines at positions 175
      and 248 were essential for dicoumarol-induced p53 degradation. NQO1 bound to wild
      type p53 and dicoumarol, which induced a conformational change in NQO1, inhibited
      this binding. Compared with wild-type p53, the hot-spot p53 mutants showed
      increased binding to NQO1, which can explain their resistance to dicoumarol
      induced degradation. NQO1 thus has an important role in stabilizing hot-spot p53
      mutant proteins in human cancer.

PMID- 14634215
TI  - Essential techniques of cancer cell culture.

PMID- 14634216
TI  - Characterization and authentication of cancer cell lines: an overview.

PMID- 14634217
TI  - Authentication of cancer cell lines by DNA fingerprinting.

PMID- 14634218
TI  - Cytogenetic characterization of tumor cell lines.

PMID- 14634219
TI  - Isolation and culture of colon cancer cell lines.

PMID- 14634220
TI  - Isolation and culture of melanoma cell lines.

PMID- 14634221
TI  - Isolation and culture of human brain tumor cells.

PMID- 14634222
TI  - Isolation and culture of renal cancer cell lines.

PMID- 14634223
TI  - Isolation and culture of prostate cancer cell lines.

PMID- 14634224
TI  - Isolation and culture of ovarian cancer cell lines.

PMID- 14634225
TI  - Isolation and culture of leukemia cell lines.

PMID- 14634226
TI  - Cell sensitivity assays: clonogenic assay.

PMID- 14634227
TI  - Cell sensitivity assays: the MTT assay.

PMID- 14634228
TI  - PARP cleavage as a means of assessing apoptosis.

PMID- 14634229
TI  - Detection of apoptosis by the TUNEL assay.

PMID- 14634230
TI  - Apoptosis measurement by annexin v staining.

PMID- 14634231
TI  - Cell adhesion assays.

PMID- 14634232
TI  - Radial monolayer cell migration assay.

PMID- 14634233
TI  - Invasion and motility assays.

PMID- 14634234
TI  - Identification of senescence in cancer cells.

PMID- 14634235
TI  - Angiogenesis assays.

PMID- 14634236
TI  - Flow cytometric DNA analysis of human cancer cell lines.

PMID- 14634237
TI  - DNA-mediated gene transfer.

PMID- 14634238
TI  - Development of drug-resistant models.

PMID- 14634239
TI  - Immortalization of human prostate cells with the human papillomavirus type 16 E6
      gene.

PMID- 14634241
TI  - Coculture of prostate cancer cells.

PMID- 14634240
TI  - The use of Matrigel to facilitate the establishment of human cancer cell lines as
      xenografts.

PMID- 14634242
TI  - Coculture of ovarian cells using porous tissue culture inserts.

PMID- 14634243
TI  - Cell culture contamination: an overview.

PMID- 14634244
TI  - Detecting Mycoplasma contamination in cell cultures by polymerase chain reaction.

PMID- 14634245
TI  - Elimination of Mycoplasma from infected cell lines using antibiotics.

PMID- 14634246
TI  - Characterization of intra-framework and guest/host interactions in the AlPO4-15
      molecular sieve by charge-density analysis.
AB  - The electron-density distribution of AlPO4-15 has been determined using high
      resolution single-crystal X-ray diffraction, and the topological properties of
      the charge density have been calculated using the 'atoms in molecules' (AIM)
      theory. Analysis of the topological properties at the bond critical points has
      been used to characterize the interactions within the framework, and between the
      framework and the extra-framework species (ammonium ions and water molecules),
      and to define atomic properties, such as volume and net charges, uniquely. A
      comparison between procrystal and multipolar representations of the density was
      performed in order to explore to what extent the former representation is likely
      to reflect the interactions in the solid. Correlation with geometrical properties
      (P-O and Al-O bond lengths, and Al-O-P angle) is found for topological charges
      obtained from the multipolar model, but not for the results from the procrystal
      representation.

PMID- 14634247
TI  - Structural refinements of high-pressure phases in germanium dioxide.
AB  - Recently, there has been substantial interest in the new high-pressure polymorphs
      of GeO2 synthesized in the laboratory. Previous investigators reported the
      synthesis of 'CaCl2-type', 'alpha-PbO2-type' and 'pyrite-type (modified-fluorite
      type)' GeO2 at pressures of 30-130 GPa in laser-heated diamond anvil cells. In
      order to provide definitive information about the new high-pressure polymorphs,
      we performed Rietveld refinements of the structures. The structure refinements
      confirm that two of these high-pressure phases do have the alpha-PbO2-type and
      pyrite-type (modified-fluorite-type) structures.

PMID- 14634248
TI  - Two-dimensionally modulated structure of the rare-earth polysulfide GdS(2-x) (x =
      0.18 approximately equal to 13/72).
AB  - The crystal structure of GdS(2-x) is determined by single-crystal X-ray
      diffraction as a 144-fold superstructure of the ZrSSi structure type. The
      superstructure is described as a two-dimensional, commensurately modulated
      structure with the superspace group P4/n(alphabeta 1/2)(00)(ss) and with alpha =
      1/4 and beta = 1/3. Structure refinements within the classical approach,
      employing the 144-fold supercell, fail because most of the superlattice
      reflections have zero intensities within the experimental resolution. Within the
      superspace approach the absent superlattice reflections are systematically
      classified as higher-order satellite reflections. Accordingly, the superspace
      approach has been used to refine the structure model comprising the basic
      structure positions and the amplitudes of the modulation functions of the three
      crystallographically independent atoms. The quality of fit to the diffraction
      data and the values of the refined parameters are independent of the assumption
      on the true symmetry (incommensurate or a 12 x 12 x 2, I-centred superlattice
      with different symmetries). Arguments of structural plausibility then suggest
      that the true structure is a superstructure with space group I4, corresponding to
      sections of superspace given by (t1, t2) equal to [(4n - 1)/48, (4m - 3)/48] or
      [(4n - 3)/48, (4m - 1)/48] (n and m are integers). Analysis of the structure,
      employing both superspace techniques (t plots) and the supercell structure model
      all show that the superstructure corresponds to an ordering of vacancies and an
      orientational ordering of S2(2-) dimers within the square layers of the S2 atoms.

PMID- 14634249
TI  - Structure of delta1-CoZn(7.8), an example of a phason pinning-unpinning
      transformation?
AB  - The novel structure of the delta1 phase in the cobalt-zinc system was determined
      by single-crystal X-ray diffraction. The structure features fused double
      icosahedra linked by edge- and face-sharing. The delta1-CoZn(7.8) structure is
      incommensurately modulated along the columnar b direction. The extent of the
      linear pentagonal antiprismatic intergrowth is limited to a maximum of two
      overlapping icosahedra because of geometric demands and radii relations. Even
      this limited fusion of icosahedra leads to strain that is believed to be the
      origin of the structural modulation. The compound was synthesized using a
      centrifugation-aided filtration method which yielded single crystals grown on
      cobalt pieces in a zinc-rich melt. The (3 + 1)-dimensional superspace group is
      F2/m(0beta0)s0 and the modulation wavevector was determined to q = 0.234b*. The
      partial amorphization of the sample when subjected to mechanical grinding is an
      indication of a metastable structure. The incommensurability of the structure may
      be seen as an ordered pinning of phasons.

PMID- 14634250
TI  - Single-crystal structure refinement of NaTiSi2O6 clinopyroxene at low
      temperatures (298 < T < 100 K).
AB  - The alkali-metal clinopyroxene NaTi(3+)Si2O6, one of the rare compounds with
      trivalent titanium, was synthesized at high temperature/high pressure and
      subsequently investigated by single-crystal X-ray diffraction methods between 298
      and 100 K. One main difference between the high- and the low-temperature form is
      the sudden appearance of two different Ti(3+)-Ti3+ interatomic distances within
      the infinite chain of the TiO6 octahedra just below 197 K. This change can be
      seen as direct evidence for the formation of Ti-Ti singlet pairs in the low
      temperature phase. Mean Ti-O bond lengths smoothly decrease with decreasing
      temperature and the phase transition is associated with a slight jump in the Ti-O
      bond length. The break in symmetry, however, causes distinct variations,
      especially with respect to the two Ti-O(apex) bond lengths, but also with respect
      to the four Ti-O bonds in the equatorial plane of the octahedron. The TiO6
      octahedron appears to be stretched in the chain direction with a slightly larger
      elongation in the P1; low-temperature phase compared with the C2/c high
      temperature phase. Polyhedral distortion parameters such as bond-length
      distortion and octahedral angle variance suggest the TiO6 octahedron in P1; to be
      closer to the geometry of an ideal octahedron than in C2/c. Mean Na-O bond
      lengths decrease with decreasing temperature and the variations in individual Na
      O bond lengths are the result of variations in the geometry of the octahedral
      site. The tetrahedral site acts as a rigid unit, which does not show pronounced
      changes upon cooling and through the phase transitions. There are neither large
      changes in bond lengths and angles nor in polyhedral distortion parameters, for
      the tetrahedral site, when they are plotted. In contrast with the C2/c-->P2(1)/c
      phase transition, found especially in LiMSi2O6 clinopyroxenes, no very large
      variations are found for the tetrahedral bridging angle. Thus, it is concluded
      that the main factor inducing the phase transition and controlling the structural
      variations is the M1 octahedral site.

PMID- 14634251
TI  - Low-temperature structure of V6O13.
AB  - The structure of the transition metal oxide V6O13, a potential cathode material
      in lithium-polymer batteries, has been studied at 95 K using single-crystal X-ray
      diffraction (XRD). A phase transition has been determined by differential
      scanning calorimetry (DSC) measurements to occur at 153 K, with a heat of
      transition of -1.98 kJ mol(-1). In this low-temperature phase, the V and O atoms
      move by up to 0.21 A out of the mirror plane they occupy in the room-temperature
      structure. It is concluded that the earlier reported space group P2(1)/a [Kawada
      et al. (1978). Acta Cryst. B34, 1037-1039] is incorrect and that a more
      appropriate choice of space group is Pc.

PMID- 14634252
TI  - Structures of potassium, sodium and lithium bis(oxalato)borate salts from powder
      diffraction data.
AB  - The crystal structures of the alkali-metal bis(oxalato)borate salts A[B(C2O4)2]
      (A = K, Na, Li) have been determined ab initio using powder diffraction data
      obtained from a laboratory diffractometer. The K compound crystallizes in the
      orthorhombic space group Cmcm and its structure has been solved by direct methods
      applied to the integrated intensities from full pattern decomposition. The Na
      compound is isostructural with the K salt, while the crystal structure of the
      highly hydroscopic Li compound differs from the other two. It has an orthorhombic
      lattice, space group Pnma, and its structure was solved by the global
      optimization method using a parallel tempering approach. In the K and Na
      structures the metal ions and complex borate ions form chains with m2m symmetry.
      Metal-oxygen bonding between the chains links them into a layer and then a
      framework with square tunnels. The coordination number of both K and Na is eight.
      The Li compound also contains chains that have .m. symmetry and are bound
      together into a three-dimensional framework. The coordination polyhedron of the
      Li atom is a square pyramid with Li lying in its base. This square pyramidal
      coordination leads to its high reactivity with moisture to give Li[B(C2O4)2]H2O
      with lithium in six coordination.

PMID- 14634253
TI  - Diffuse X-ray scattering from 4,4'-dimethoxybenzil, C16H14O4: analysis via
      automatic refinement of a Monte Carlo model.
AB  - A recently developed method for fitting a Monte Carlo computer-simulation model
      to observed single-crystal diffuse X-ray scattering has been used to study the
      diffuse scattering in 4,4'-dimethoxybenzil, C16H14O4. A model involving only nine
      parameters, consisting of seven intermolecular force constants and two
      intramolecular torsional force constants, was refined to give an agreement
      factor, omegaR = [sigma omega(deltaI)2/sigma omegaI2(obs)](1/2), of 18.1% for 118
      918 data points in two sections of data. The model was purely thermal in nature.
      The analysis has shown that the most prominent features of the diffraction
      patterns, viz. diffuse streaks that occur normal to the [101] direction, are due
      to longitudinal displacement correlations along chains of molecules extending in
      this direction. These displacements are transmitted from molecule to molecule via
      contacts involving pairs of hydrogen bonds between adjacent methoxy groups. In
      contrast to an earlier study of benzil itself, it was not found to be possible to
      determine, with any degree of certainty, the torsional force constants for
      rotations about the single bonds in the molecule. It is supposed that this result
      may be due to the limited data available in the present study.

PMID- 14634254
TI  - Molecular and crystal properties of E-1,2-bis(3-methoxy-2-thienyl)ethene: static
      disorder in the crystal.
AB  - The crystal structure of E-1,2-bis(3-methoxy-2-thienyl)ethene (C12H12O2S2) has
      been determined at five different temperatures, i.e. room temperature (293), 223,
      173, 123 and 93 K. The solid-state work is complemented by the results of
      theoretical calculations of energies, geometries, difference electron densities
      and atomic charges of the free molecule. Analysis revealed static disorder caused
      by a higher energy conformer of the title compound, probably contaminating the
      crystal during its growth. The results support the contention that the electrical
      properties are mainly governed by the carbon backbone.

PMID- 14634255
TI  - Monitoring structural transformations in crystals. 6. The [4 + 4]
      photodimerization of 9-methylanthracene.
AB  - The structural changes in a crystal of 9-methylanthracene (1) during the [4 + 4]
      photodimerization were monitored by means of X-ray diffraction. This is the first
      example in the literature of such a study of a [4 + 4] photodimerization. The
      results obtained were compared with data for the [2 + 2] photodimerization. The
      shape of the product molecules and their preferred packing can explain the
      crystal disintegration. This was the reason that the reaction was monitored only
      to 28% completion. As far as could be determined the reaction proceeds with a
      constant rate. The cell volume increases at the beginning of the transformation
      and decreases afterwards. The product molecules do not assume a fixed position in
      the crystal during the photo-reaction, but move in a smooth way that includes a
      rotational component. The movements of the reactant are much smaller. Movements
      of molecules characterized by a rotational component were also observed in the
      case of the [2 + 2] photodimerization of 5-benzylidene-2-benzylcyclopentanone and
      5-benzylidene-2-(4-chlorobenzyl)-cyclopentanone. The distance between the
      reacting atoms of the adjacent monomer molecules of (1) decreases with the degree
      of reaction completion, but more slowly than in the case of the [2 + 2]
      photodimerizations cited above. The orientation of the neighbouring monomer
      molecules changes during the phototransformation so that the monomer pair
      resembles the dimer product.

PMID- 14634256
TI  - Protonation site and hydrogen bonding in anhydrous and hydrated crystalline forms
      of doxazosin mesylate from powder data.
AB  - The three-dimensional solid-state structures of two modifications of doxazosin
      mesylate (C23H26N5O5)+.(CH3SO3)-, 4-amino-2-[4-[(2,3-dihydro-1,4-benzodioxin-2
      yl)carbonyl]piperazin-1-yl]-6,7-dimethoxyquinazoline methanesulfonate, a commonly
      used antihypertensive agent, have been determined by synchrotron X-ray powder
      diffraction. An anhydrous form (A) and a dihydrate form (dG) crystallize in
      monoclinic space groups. In both forms the doxazosin molecule is protonated at
      the N1 atom of the quinazoline bicycle. The N1 atom, and the amino H atoms and O
      atoms of the mesylate moieties are involved in three-dimensional hydrogen-bonding
      networks, while solvent water molecules and carboxamide O atoms are also
      incorporated in a hydrogen-bonding network in dG.

PMID- 14634257
TI  - Variable-temperature neutron diffraction studies of the short, strong N...O
      hydrogen bonds in the 1:2 co-crystal of benzene-1,2,4,5-tetracarboxylic acid and
      4,4'-bipyridyl.
AB  - The 1:2 adduct of benzene-1,2,4,5-tetracarboxylic acid and 4,4'-bipyridyl at 100
      K has been studied by single-crystal neutron diffraction at 20, 200 and 296 K.
      The structure contains two short, strong N...O hydrogen bonds: one O-H...N
      hydrogen bond [O...N 2.6104 (17) A at 20 K] and one short N-H...O hydrogen bond
      [N...O 2.5220 (17) A at 20 K]. The N-H distance in the N-H...O hydrogen bond
      changes from 1.207 (3) A at 20 K to 1.302 (4) A at 296 K and the N...O distance
      increases to 2.5315 (16) A at 296 K. At 200 K the H atom lies in an intermediate
      position 1.251 (6) A from the N atom with an N...O separation of 2.520 (4) A. The
      O-H...N hydrogen bond, on the other hand, does not change with temperature.

PMID- 14634258
TI  - New electron diffraction method to identify the chirality of enantiomorphic
      crystals.
AB  - A new CBED (convergent-beam electron diffraction) method is proposed for the
      identification of the chirality of enantiomorphic crystals, in which asymmetry in
      the intensity of the reflections of Bijvoet pairs in an experimental symmetrical
      zone-axis CBED pattern is compared with that of a computer-simulated CBED
      pattern. The intensity difference for reflections of these Bijvoet pairs results
      from multiple scattering (dynamical nature of electron diffraction) among
      relevant Bijvoet pairs of reflections, each pair of which has identical amplitude
      and different phase angles. Therefore, the crystal thickness where chiral
      identification is made with the present method is limited by the extinction
      distance of Bijvoet pairs of reflections relevant to multiple scattering to
      produce the intensity asymmetry, which is usually of the order of a few tens of
      nanometers. With the present method, a single CBED pattern is sufficient and
      chiral identification can be made for all the possible enantiomorphic crystals
      that are allowed to exist in crystallography.

PMID- 14634260
TI  - The neurology of art--the example of Giorgio de Chirico.

PMID- 14634261
TI  - The metaphysical art of Giorgio de Chirico. Migraine or epilepsy?
AB  - It has been suggested that the great Italian painter Giorgio de Chirico (1888
      1978), who developed the unique style of 'metaphysical art', suffered from
      migraine and used some of his morbid manifestations as a source of inspiration
      for his paintings. Yet, whereas many of the symptoms that de Chirico described
      are rare in migraine, they are frequently encountered in patients with temporal
      lobe epilepsy. Here we rediscuss de Chirico's symptoms critically and suggest
      that, if his symptoms were of neurological origin, they rather relate to temporal
      lobe epilepsy than migraine.

PMID- 14634262
TI  - An epidemiological study of migraine with aura in the San Severo general
      population: a pilot research project of cooperation between neurologists and
      general practitioners.
AB  - OBJECTIVES: (A) To define the lifetime prevalence of migraine with aura (MA) in
      patients recruited in general practices for an epidemiologic study by the
      University of Parma Headache Centre from the general population of San Severo,
      Italy, and (B) to assess the recognition of MA in general practice. METHODS: The
      study was conducted over a period of 5 consecutive months (January to May 2001)
      on patients aged 18-65, taken from the following general practice populations:
      (a) from the patient population of 4 general practitioners (GPs; 3,616 patients)
      and (b) from the patient population of 12 GPs (12,996 patients). The clinical
      diagnosis of MA was subsequently confirmed by a headache specialist. RESULTS: For
      objective A, 648 patients (420 women and 228 men) were interviewed; MA diagnosis
      was confirmed in 10 patients (7 women and 3 men), lifetime MA prevalence being
      1.5%. For objective B, 150 'suspected' MA cases (96 women and 54 men) were
      reported by the 12 GPs; however, the diagnosis of MA was confirmed in only 3
      cases (2 women and 1 man). CONCLUSION: The prevalence of MA observed in our small
      sample of the general practice patient population was comparable with that
      observed in the general population of San Severo, Italy. The results also suggest
      that GPs may be overestimating the number of cases of MA in their patient
      population.

PMID- 14634263
TI  - Induction of apoptosis of CD4+ T cells by immunomodulatory therapy of multiple
      sclerosis with glatiramer acetate.
AB  - Glatiramer acetate (GA), a mixture of synthetic polypeptides, has beneficial
      effects on the clinical course and the MRI-defined disease activity of patients
      with multiple sclerosis (MS). In MS, evidence has been provided that the
      apoptosis of disease-relevant T cells is dysregulated. In this study, we
      investigated the effect of GA on T cell apoptosis, T cell activation, and
      cytokine profile of lymphocytes derived from 19 relapsing-remitting MS patients
      during the first year of GA therapy. Analysis of blood samples obtained every 6
      weeks showed an increase in apoptotic T helper cells after 30 weeks of therapy.
      This effect remained until the end of the study and was accompanied by an
      increase in activated T cells and interleukin-4-producing lymphocytes. Thus, in
      addition to the established effect of GA on the cytokine network, GA-mediated
      immunomodulation might involve the apoptotic elimination of T helper cells.

PMID- 14634264
TI  - Impact of emergency room neurologists on patient management and outcome.
AB  - The frequency and impact of in-patient assessment by a neurologist in the
      emergency room (ER) setting remain largely underestimated. The objective of our
      study was to analyse the impact of neurologist in-patient management. METHODS:
      Over a period of 12 months, we prospectively recorded the demographics of
      patients requiring examination in the ER, the ER team's tentative neurological
      diagnosis, the neurology team's final diagnosis and patient outcomes. The time
      interval between admission, call for a neurologist and the assessment by the
      neurologist were recorded. RESULTS: Assessments by neurologists were performed in
      14.7% (1,679/11,421) of all patients admitted to the ER. The mean time between
      admission and examination was 32 (+/- 36) min, irrespective of the day of the
      week, and dependent on the tentative diagnosis: shorter for stroke and status
      epilepticus (p < 0.05) and longer for confusion and vertigo (p < 0.05). The
      initial causes for examination were: stroke (33.1%), epilepsy (20%), loss of
      consciousness (9%), headaches (9%), confusion (5.4%), peripheral nervous system
      disorders (4.4%), vertigo (4.2%), cognitive dysfunctions (4%), gait disorders
      (3.2%) and miscellaneous (7.1%). Overall, false positive or negative diagnoses
      were produced by the ER in 37.3 and 36.6% of ER admissions, respectively. A
      complete change of diagnosis by the neurologist was found in 52.5% of patients.
      Of the patients undergoing a neurological examination, 18.4% were able to go
      home, 31.8% were admitted to the stroke unit, 32.4% to the general neurology unit
      and 17.4% to other departments. CONCLUSION: Our study stresses the need for a
      neurologist in the ER, both in quantitative terms and for the benefit of patient
      management.

PMID- 14634265
TI  - Alpha-tocopherol and NADPH in the erythrocytes and plasma of multiple sclerosis
      patients. Effect of interferon-beta-1b treatment.
AB  - OBJECTIVES: To investigate the influence of interferon-beta-1b (INF-beta-1b)
      therapy on blood antioxidants (alpha-tocopherol and NADPH) in multiple sclerosis
      (MS). PATIENTS AND METHODS: Patients with relapsing-remitting MS (n = 14) have
      been studied during 6 months of INF-beta-1b therapy. alpha-Tocopherol was
      determined by HPLC and UV or electrochemical detection; NADPH was quantified
      spectrophotometrically. RESULTS: The erythrocyte alpha-tocopherol level was
      reduced (p < 0.001) before treatment, but had regained the control level by 6
      months of therapy. The plasma alpha-tocopherol/lipid ratios were constant during
      therapy. Plasma triglyceride levels were transiently increased (p = 0.0270) after
      1 month of treatment. INF-beta-1b had also induced a transient decrease in NADPH
      after 1 month, but thereafter the level returned to approximately the initial
      value (p = 0.0248). CONCLUSION: INF-beta-1b seems to exert a sparing effect
      toward the erythrocyte alpha-tocopherol content. The fall in NADPH in parallel to
      the rise in plasma triglycerides suggests stimulation of fatty acid synthesis by
      INF-beta-1b.

PMID- 14634266
TI  - Diffuse white matter lesions in carbon disulfide intoxication: microangiopathy or
      demyelination.
AB  - Long-term exposure to carbon disulfide (CS(2)) may induce diffuse encephalopathy
      with parkinsonism, pyramidal signs, cerebellar ataxia, and cognitive impairments,
      as well as axonal polyneuropathy. The pathogenic mechanisms of diffuse
      encephalopathy are unclear, although vasculopathy and toxic demyelination have
      been proposed. Recently, we have encountered a patient who developed headache,
      limb tremors, gait disturbance, dysarthria, memory impairment, and emotional
      lability after long-term exposure to CS(2). The brain magnetic resonance images
      (MRI) showed diffuse hyperintensity lesions in T(2)-weighted images in the
      subcortical white matter, basal ganglia, and brain stem. The brain computed
      tomography perfusion study revealed a diffusely decreased regional cerebral blood
      flow and prolonged regional mean transit time in the subcortical white matter and
      basal ganglion. To our knowledge, there have been few reports demonstrating
      diffuse white matter lesions in chronic CS(2) encephalopathy using brain MRI. In
      addition, the (99m)Tc-TRODAT-1 single photon emission computed tomography showed
      a normal uptake of the dopamine transporter, indicating a normal presynaptic
      dopaminergic pathway. We conclude that diffuse white matter lesions may develop
      after chronic exposure to CS(2), possibly through microangiopathy. In addition,
      CS(2) poisoning can be considered as one of the causes of chronic
      leukoencephalopathy.

PMID- 14634267
TI  - Beneficial effect of steroid pulse therapy on acute viral encephalitis.
AB  - Corticosteroids are often used in the treatment of acute viral encephalitis,
      although the efficacy of corticosteroid therapy has not been proven. We examined
      the effects of high-dose corticosteroid therapy on acute viral encephalitis in 5
      patients with progressive disturbances of consciousness. In 3 patients who were
      treated within 5 days after the onset of illness, pulse therapy dramatically
      reduced the degree of consciousness disturbance. They became alert within 24 h,
      and then neurological symptoms gradually improved. Corticosteroid therapy in the
      other 2 patients, in whom treatment was started more than 3 weeks after the onset
      of illness, was not as effective, but repeated therapy at 2-week intervals
      resulted in complete recovery. These findings suggest that high-dose
      corticosteroid therapy is effective, particularly for disturbances of
      consciousness, an important prognostic factor in acute viral encephalitis.

PMID- 14634268
TI  - Evaluation of baroreflex sensitivity by the sequence method using blood pressure
      oscillations and R-R interval changes during deep respiration.
AB  - BACKGROUND: Baroreflex sensitivity assessments have been considered to be
      important to evaluate cardiac autonomic neuropathy. The phenylephrine method,
      Valsalva maneuver or sequence method at rest caused several problems. We
      evaluated the usefulness of the sequence method during deep respiration. METHOD:
      Baroreflex sensitivity was evaluated in 20 normal volunteers and 50 patients with
      Parkinson's disease. R-R intervals and systolic blood pressures were obtained by
      electrocardiogram and tonometry using a continuous blood pressure monitoring
      system. The sequence method is an evaluation of baroreflex sensitivity using
      sequences of 3 or more consecutive beats for 4 min. Baroreflex sensitivity was
      also assessed by the Valsalva maneuver at 5 beats before the peak systolic blood
      pressure of phase IV. The slope of the linear interrelationship between systolic
      blood pressure and the following R-R interval, i.e. baroreflex sensitivity (ms/mm
      Hg), was calculated with a correlation coefficient greater than 0.8. RESULT: The
      mean value of baroreflex sensitivity obtained by the Valsalva maneuver was 7.91
      in normal volunteers and 5.35 in patients with Parkinson's disease; the one
      obtained by the sequence method at rest was 9.10 in normal volunteers and 8.42 in
      patients with Parkinson's disease, and the one obtained by the sequence method
      during deep respiration was 10.23 in normal volunteers and 6.73 in patients with
      Parkinson's disease. In some cases with Parkinson's disease, baroreflex
      sensitivities could not be found, whereas in all patients with Parkinson's
      disease, the sequence method during deep respiration could be used for
      evaluations. Significant correlations were found among the baroreflex
      sensitivities obtained by the Valsalva maneuver, and the sequence method at rest
      or during deep respiration in normal volunteers and patients with Parkinson's
      disease. CONCLUSIONS: The baroreflex sensitivity obtained by the sequence method
      during deep respiration could be investigated noninvasively in all cases with PD,
      being thus a useful method for clinical evaluation of baroreflex sensitivity.

PMID- 14634269
TI  - An electrophysiological study of the deep peroneal sensory nerve.
AB  - The electrodiagnosis of peripheral neuropathy is often based on nerve conduction
      abnormalities in sensory nerves of the lower extremities. We performed nerve
      conduction studies of the deep peroneal sensory nerve prospectively in 63 limbs
      of 38 normal subjects. The sensory amplitudes showed a decreasing trend with
      increasing age. 21% of subjects had absent sensory potentials, especially those
      in the older age groups. This was seen in contrast with superficial peroneal and
      sural potentials, which were universally present. Although the deep peroneal
      sensory nerve is located in the distal lower limb, it should be used with caution
      in evaluating peripheral neuropathy, in view of the frequent occurrence of absent
      potentials even in asymptomatic normal subjects.

PMID- 14634270
TI  - Multiple sclerosis after allergen-specific immunotherapy and influenza
      vaccination.

PMID- 14634271
TI  - Simultaneous occurrence of a central and a peripheral positional nystagmus during
      the Dix-Hallpike manoeuvre.

PMID- 14634272
TI  - Apoptosis in ventricular myocytes: the role of tumor suppressor proteins.
AB  - Apoptosis or programmed cell death is an important physiologic event crucial for
      the selective removal of damaged or unwanted cells from body tissues. In the
      cardiovascular system, apoptosis has been observed in the vasculature and
      myocardium. Untimely or inappropriate myocardial cell loss through an apoptotic
      process may contribute to ventricular remodeling and the ultimate demise of
      ventricular function following injury. Therapeutic interventions designed to
      modulate or prevent myocardial apoptotic cell loss may therefore prove beneficial
      in maintaining cardiac function. Incite into the molecular mechanisms that govern
      apoptosis in mammalian cells has led to the identification of several key factors
      that promote or prevent the apoptotic process. In this report, we discuss
      putative regulators of cardiac cell apoptosis with specific reference to the
      tumor suppressor proteins, p53 and Rb. The interplay between these factors, as
      well as the anti-apoptotic molecules related to the Bcl-2 the family are
      discussed in the context of the heart under normal and disease conditions.

PMID- 14634273
TI  - Caveolin-1, a metastasis-related gene that promotes cell survival in prostate
      cancer.
AB  - Metastasis represents the ultimate target in cancer therapy as this complex
      biological process is the direct cause of mortality for a variety of human
      malignancies. The current high level of mortality from prostate cancer results in
      large part from the inexorable growth of overt or occult metastasis present at
      the time of diagnosis. Currently, there are no curative therapies for metastatic
      prostate cancer. To better understand the metastatic phenotype in prostate
      cancer, we developed a strategy to identify mRNAs that are expressed
      differentially in cell lines derived from primary versus metastatic mouse
      prostate cancer using differential display-PCR. In using this system a number of
      metastasis-related sequences were identified including a cDNA that encodes
      caveolin-1. Caveolin-1 was found to be overexpressed not only in metastatic mouse
      prostate cancer, but also in human metastatic disease. Recent studies have
      indicated that suppression of caveolin-1 expression induces androgen sensitivity
      in high caveolin-1, androgen-insensitive mouse prostate cancer cells derived from
      metastases. Conversely, overexpression of caveolin-1 leads to androgen
      insensitivity in low caveolin, androgen-sensitive mouse prostate cancer cells.
      Caveolin-1, therefore, is both a metastasis-related gene as well as a candidate
      androgen resistance gene for prostate cancer in man. Interestingly, recent
      studies also point to a potential role for caveolin-1 in the resistance of
      various malignancies to multiple antineoplastic agents. The linkage of caveolin-1
      expression with the androgen-resistant phenotype in prostate cancer and the
      multidrug resistance phenotype in various solid tumors establishes a novel
      paradigm for understanding these clinically important and now potentially related
      processes in malignant progression.

PMID- 14634274
TI  - Epidermal growth factor receptor: its role in Drosophila eye differentiation and
      cell survival.
AB  - The Drosophila epidermal growth factor receptor (EGFR), functioning through the
      Ras/Raf/MAPK pathway, promotes cell proliferation and differentiation. Recent
      work has demonstrated that EGFR functions via the same Ras/Raf/MAPK pathway to
      promote cell survival. This review summarizes the role of EGFR in differentiation
      and survival during Drosophila eye development.

PMID- 14634275
TI  - Role of G1 phase in the UV-induced apoptosis of EL-4 mouse lymphoma cells.
AB  - Although UV is known to induce apoptotic cell death to various animal cells,
      relationship between cell cycle and UV-induced apoptosis is still unclear. In
      this study, we investigated the role of G1 phase in UV-induced apoptosis by using
      EL-4 mouse lymphoma cells which have wild type p53. After 500 J/m2 UV
      irradiation, an increase of apoptotic fraction was accompanied by cell cycle
      accumulation in the G1 phase. Apoptotic fraction after UV-exposure was remarkably
      augmented by treatment with 2-AP, a G1 checkpoint inhibitor. In contrast,
      aphidicolin, an inhibitor of DNA polymerase-alpha, suppressed the rate of
      apoptotic fraction. These results suggest that mandatory cell cycle progression
      from G1 to S leaves the damaged DNA unrepaired and may increase the apoptotic
      fraction. To investigate the precise mechanism in the G1 phase, UV was exposed to
      the G1-synchronized cells and apoptotic fraction was serially observed.
      Synchronized EL-4 cells passed through the G1 phase in 8 h. Within the G1 phase,
      late-G1 cells (6 h after M) were more sensitive to UV-induced apoptosis than
      early-G1 cells (2 h after M) (49.7 +/- 9.0% vs. 41.5 +/- 8.5%, p < 0.05). In HL
      60 cells, lacking in p53 expression, such a difference was not observed. Western
      blot analysis revealed that expression of p53 in synchronized EL-4 cells was
      increasingly enhanced during G1 phase. After UV-exposure, p53 expression
      gradually decreased in early-G1 cells, but it was kept at almost the same level
      in late-G1 cells. In addition, bcl-2 expression in early-G1 cells showed a more
      rapid and larger increase than that in late-G1 cells. These results suggest that
      susceptibility of the G1 cells to UV-induced apoptosis depends on their position
      within the G1 phase, and late-G1 is more sensitive than early-G1. Sensitivity to
      UV-induced apoptosis is closely related to the expression level of p53 and bcl-2
      proteins. Early-G1 cells may be able to take enough time to repair damaged DNA
      until they reach the G1 checkpoint compared to the late-G1 cells.

PMID- 14634276
TI  - Fas-mediated apoptosis in Jurkat cells is suppressed in the pre-G2/M phase.
AB  - The relationship between the cell cycle and Fas-mediated apoptosis was
      investigated using Jurkat cells. Analysis of the inducibility of apoptosis by
      anti-Fas antibody during the cell cycle synchronized by the thymidine double
      block method, showed that apoptosis was induced in only 50% of the G2/M phase
      cells, while most of cells in the other phases underwent apoptosis. These
      observations indicate that G2/M phase cells are more resistant to Fas-mediated
      apoptosis than cells in other phases. Furthermore, a detailed analysis of G2/M
      phase found that only 20-30% of the cells underwent apoptosis 12 h after the
      removal of the second thymidine block (pre-G2/M phase). This suggests that Fas
      mediated apoptosis is potently suppressed during the pre-G2/M phase. A possible
      explanation for the observation that cells in the pre-G2/M phase are less
      sensitive to anti-Fas antibody is lower expression level of Fas. To test this
      possibility, Fas expression levels on the cell surface during the cell cycle were
      examined. The content of Fas on the cell surface, however, did not change
      appreciably during the cell cycle. Thus, the suppression of apoptosis in the pre
      G2/M phase is determined downstream after the receipt of the apoptotic signal
      through Fas.

PMID- 14634277
TI  - Cyclooxygenase-independent induction of p21WAF-1/cip1, apoptosis and
      differentiation by L-745,337, a selective PGH synthase-2 inhibitor, and
      salicylate in HT-29 cells.
AB  - In order to dissect out cyclooxygenase-dependent from cyclooxygenase-independent
      mechanisms in the antiproliferative effects of selective prostaglandin H synthase
      (PGHS)-2 inhibitors, we compared the effects of L-745,337 (a highly selective
      PGHS-2 inhibitor) with sodium salicylate (a weak PGHS inhibitor) on prostanoid
      production, induction of the cyclin-dependent kinase inhibitor p21WAF-1/cip1,
      mutant p53 (m273-p53) levels, apoptosis and differentiation in human colon
      adenocarcinoma HT-29 cells. L-745,337 dose-dependently suppressed the
      cyclooxygenase activity of HT-29 cells (IC50: 0.24 microM). Four-day treatment
      with L-745,337 caused a concentration-dependent inhibition of cell growth (IC50:
      0.9 mM) associated with the induction of p21WAF-1/cip1 and an increase in the
      proportion of apoptotic nuclei (EC50: 0.1 and 0.34 mM, respectively) while
      reducing the levels of m273-p53 (IC50: 0.2 mM). Sodium salicylate, at the
      concentration of 10 mM that did not affect prostanoid formation, caused a 60%
      reduction of cell growth associated with a 3-fold induction of p21WAF-1/cip1 and
      a 60% increase in the proportion of apoptotic nuclei. Ultrastructural analysis
      showed that L-745,337 (0.5 mM) and sodium salicylate (10 mM) caused the induction
      of a differentiated phenotype. We conclude that high concentrations of L-745,337
      and sodium salicylate inhibit colon cancer cell growth by a mechanism unrelated
      to cyclooxygenase inhibition that may involve p53-independent induction of the
      tumor suppressor p21WAF-1/cip1.

PMID- 14634278
TI  - Elimination of extrachromosomal c-myc genes by hydroxyurea induces apoptosis.
AB  - Hydroxyurea (HU) increases extrachromosomal DNA elimination in tumor cell lines.
      The c-myc oncogene is one of the many relevant amplified genes contained within
      the extrachromosomal DNA compartment. Spontaneous loss of amplified copies of c
      myc induces terminal differentiation and apoptosis in the human HL-60 leukemia
      cell lines. In the present study, we evaluate HU's ability to induce apoptosis by
      eliminating extrachromosomally located c-myc oncogene in human tumor cell lines.
      The consequences of eliminating extrachromosomal DNA by HU were explored in two
      different cell lines using the TdT assay and acridine orange/ethidium bromide
      labeling. COLO 320 clone 3 and COLO 320 clone 21 cell lines contain the same
      number of amplified copies of c-myc oncogene, but located respectively on
      extrachromosomal DNA, and intrachromosomally in homogeneously staining regions.
      HU induced apoptosis in the COLO 320 clone 3 cell line by a time and
      concentration dependent mechanism but could not induce apoptosis in the COLO 320
      clone 21 cell line. These results suggested that HU-induced apoptosis in COLO 320
      cell lines depends on elimination of extrachromosomal amplified copies of the c
      myc oncogene. The ability of HU to eliminate extrachromosomally amplified copies
      of the c-myc oncogene and to induce apoptosis should be considered when targeting
      malignancies with amplification of the c-myc oncogene in an extrachromosomal
      site.

PMID- 14634279
TI  - Combined use of radioimagers and radioactive 3'OH DNA nick end labelling to
      quantify apoptosis in cell lines and tissue sections: applications to virus
      induced apoptosis.
AB  - DNA fragmentation is a key feature of the degradation phase of apoptosis. In this
      work we have developed an assay, based on radioimager (beta-IMAGER and micro
      IMAGER) quantification of radioactive nick end labelling (RANEL), which is
      quantitative, rapid and sensitive to study in vitro and in vivo induced
      apoptosis. To establish the technique, in vitro apoptosis of T cell lines was
      induced by stimulation of the Fas receptor; cells were labelled using TdT
      mediated [alpha-33P] dCTP nick end labelling, after which then radioactivity was
      quantified using a beta-IMAGER. We have also shown that the RANEL method can be
      applied to the quantification and visualisation, by micro-IMAGER analysis, of
      liver tissue sections from mouse Fas-induced fulminant hepatitis or from Dengue-1
      virus infected individuals. Finally, this system has also been used to detect
      apoptosis induced by rabies virus in Jurkat T cells. These data have established
      a large field of application for the RANEL assay.

PMID- 14634280
TI  - Regulation of cell survival in CD95-induced T cell apoptosis: role of NF-kappa
      B/Rel transcription factors.
AB  - The activity of NF-kappa B/Rel transcription factors can inhibit the apoptosis
      induced by TNF, UV or cancer therapy drugs in a number of cell types, including
      human T lymphocytes. Furthermore, the NF-kappa B/Rel inducer, phorbol-12
      myristate-13-acetate (PMA), has been reported to suppress the CD95-induced
      apoptosis of human T lymphocytes. To verify whether the survival-enhancing effect
      of PMA required NF-kappa B/Rel activity, we generated two Jurkat cell sublines
      (AL.7 and AL.8) transfected with a pCMV4-I kappa B alpha construct, and two (AL.3
      and AL.5) with the void pCMV4 vector. Compared to wild type, AL.3 and AL.5 cells,
      the AL.7 and AL.8 sublines displayed markedly lower amounts of NF-kappa B/Rel
      nuclear complexes and a reduced expression of a kappa B-controlled CAT reporter
      gene after 1 and 4 h of incubation with PMA, respectively. All the five cell
      types displayed negligible levels of apoptosis when cultured with medium or PMA
      alone; when stimulated with the mAb CH-11, the AL.7 and AL.8 sublines displayed
      apoptotic responses only slightly (<0.5 fold) higher than control cells. On the
      other hand, the salvage activity of PMA was partially impaired in the AL.7 and
      AL.8 sublines. PMA inhibited apoptosis by >85% in wild type, AL.3 and AL.5 cells
      and by <60% in the AL.7 and AL.8 sublines; the apoptosis percentages in the mAb
      CH-11 + PMA cultures of the I kappa B alpha-transfected cells were >4-fold higher
      than in control cells. We conclude that the inhibition of the CD95-induced
      apoptosis by PMA relies on both NF-kappa B/Rel-dependent and -independent
      mechanisms. The partial contribution of these nuclear factors to the suppression
      of apoptosis indicates that the NF-kappa B/Rel activity can influence the extent
      of the CD95-induced T cell death.

PMID- 14634281
TI  - Cytokines as suppressors of apoptosis.
AB  - Many cytokines have been isolated by their ability to induce growth and have been
      called growth factors. But these cytokines are also essential to induce cell
      viability, and cell viability and growth can be separately regulated. Using as
      examples myeloid hematopoietic cells, lymphocytes and neuronal cells, in vitro
      and in vivo studies have shown the role of cytokines in inducing viability of
      different cell types during development to mature cells. Some cytokines can act
      on more than one cell type. Cytokines induce viability of normal and cancer cells
      by suppressing the apoptotic machinery activated by wild-type p53, or by
      cytotoxic agents including irradiation and compounds used in cancer chemotherapy.
      Cytokines can be used to decrease apoptosis in normal cells and inhibition of
      cytokine activity may improve cancer therapy by enhancing apoptosis in cancer
      cells. The apoptosis suppressing function of cytokines is mediated by changing
      the balance in the activity of apoptosis inducing and suppressing genes.
      Apoptosis suppression is upstream of caspase activation in the apoptotic process.
      Cytokines can suppress multiple pathways leading to apoptosis, only some of which
      were suppressed by other agents such as some antioxidants, Ca(2+)-mobilizing
      compounds and protease inhibitors.

PMID- 14634282
TI  - Adenosine-induced cell death: evidence for receptor-mediated signalling.
AB  - Adenosine modulates the proliferation, survival and apoptosis of many different
      cell types, ranging from epithelial, endothelial and smooth muscle cells, to
      cells of the immune and neural lineages. In this review, we critically discuss
      the available in vitro and in vivo data which support a role for adenosine in
      both development-associated apoptosis, and in diseases characterized by either
      pathologically increased cell death (e.g., ischemia, trauma and aging-associated
      neurodegeneration) or abnormally reduced spontaneous apoptosis (e.g., cancer).
      Particular emphasis is given to the possible role of extracellular adenosine
      receptors, since these may represent novel and attractive molecular targets for
      the pharmacological modulation of apoptosis. In some instances, adenosine-induced
      cell death has been demonstrated to require entry of the nucleoside inside cells;
      however, in many other cases, activation of specific adenosine extracellular
      receptors has been demonstrated. Of the four G protein-coupled adenosine
      receptors so far identified, the A2A and the A3 receptors have been specifically
      implicated in modulation of cell death. For the A3 receptor, results obtained by
      exposing both cardiomyocytes and brain astrocytes to graded concentrations of
      selective agonists suggest induction of both cell protection and cell death. Such
      opposite effects, which likely depend on the degree of receptor activation, may
      have important therapeutic implications in the pharmacological modulation of
      cardiac and brain ischemia. For the A2A receptor, recent intriguing data suggest
      a specific role in immune cell death and immunosuppression, which may be relevant
      to both adenosine-deaminase-immunodeficiency syndrome (a pathology characterized
      by accumulation of adenosine to toxic levels) and in tumors where induction of
      apoptosis via activation of specific extracellular receptors may be desirable.
      Finally, preliminary data suggest that, in a similar way to the adenosine
      deaminase-immunodeficiency syndrome, the abnormal accumulation of adenosine in
      degenerative muscular diseases may contribute to muscle cell death. Although the
      role of adenosine receptors in this effect still remains to be determined, these
      data suggest that adenosine-induced apoptosis may also represent a novel
      pathogenic pathway in muscular dystrophies.

PMID- 14634283
TI  - Roles of cyclin D1 and related genes in growth inhibition, senescence and
      apoptosis.
AB  - It is now apparent that apoptosis is closely linked to the control of cell cycle
      progression. During the G1 to S progression, cyclin D1, p53, and the cyclin
      dependent kinase inhibitors p21WAF1 and p27kip1 can play roles in induction of
      apoptosis. During the G2 and M phases, premature activation of Cdk1 can cause
      cells to enter mitotic catastrophe, which results in apoptosis. In this review we
      focus on factors acting during G1 and S, particularly cyclin D1, and their
      effects on cell growth, senescence and apoptosis. We emphasize that cyclin D1 can
      have diverse effects on cells depending on its level of expression, the specific
      cell type, the cell context and other factors. Possible mechanisms by which
      cyclin D1 exerts these diverse effects, via cyclin dependent kinase-dependent and
      -independent pathways, are discussed.

PMID- 14634284
TI  - IL-3 induces apoptosis in a ras-transformed myeloid cell line.
AB  - Growth factors promote cell survival and proliferation. Homeostasis is maintained
      by programmed cell death which occurs when the growth stimulus is withdrawn, in
      response to negative growth regulators such as interferons, TNF-alpha and CD95
      ligand, or following differentiation. Although acutely-transforming oncogenes
      often overcome the need for growth factors, growth regulatory cytokines can
      influence proliferative responses of transformed cells. In this study we
      investigated the effects of IL-3 on the proliferative responses of parental bone
      marrow-derived 32D cells and cells transformed with ras and abl oncogenes. We
      show that treatment of ras-transformed 32D cells with IL-3 reduced proliferative
      responses and decreased colony-forming ability. These effects were exacerbated in
      the absence of serum and associated with inhibition of tyrosine kinase activity,
      down-regulation of RAS and MYC expression, and induction of apoptosis as
      indicated by DNA fragmentation. In contrast, treatment of parental 32D cells with
      IL-3, which is obligatory for cell survival and proliferation, increased tyrosine
      kinase activity, upregulated MYC and RAS expression and maintained DNA integrity.
      With abl-transformed cells, proliferation and colony-forming ability were also
      inhibited by IL-3. Tyrosine kinase activity and MYC expression were reduced, but
      early apoptosis was not evident. Calcium uptake however, was stimulated by IL-3
      in both parental and oncogene-transformed cells. These results suggest that
      threshold levels of tyrosine kinase activity are necessary for cell survival and
      proliferation and that with ras-transformed cells, IL-3 treatment may result in
      this threshold being breached. We conclude that in some situations, growth
      promoting cytokines can inhibit proliferation of transformed cells and induce
      cell death by apoptosis.

PMID- 14634285
TI  - Palmitate induces apoptosis via a direct effect on mitochondria.
AB  - The fatty acid palmitate can induce apoptosis. Here we show that the palmitate
      induced dissipation of the mitochondrial transmembrane potential (Delta Psi m),
      which precedes nuclear apoptosis, is not prevented by inhibitors of mRNA
      synthesis, protein synthesis, caspases, or pro-apoptotic ceramide signaling.
      However, the mitochondrial and nuclear effects of palmitate are inhibited by
      overexpression of anti-apoptotic proto-oncogene product Bcl-2 and exacerbated by
      2-bromo-palmitate as well as by carnitine. The cytoprotective actions of Bcl-2,
      respectively, is not antagonized by etomoxir, an inhibitor of carnitine palmitoyl
      transferase 1 (CPT1), suggesting that the recently described physical interaction
      between CPT1 and Bcl-2 is irrelevant to Bcl-2-mediated inhibition of palmitate
      induce apoptosis. When added to purified mitochondria, palmitate causes the
      release of soluble factors capable of stimulating the apoptosis of isolated
      nuclei in a cell-free system. Mitochondria purified from Bcl-2 over-expressing
      cells are protected against the palmitate-stimulated release of such factors.
      These data suggest that palmitate causes apoptosis via a direct effect on
      mitochondria.

PMID- 14634286
TI  - Ethyl-nitrosourea transformed astrocytes exhibit mitochondrial membrane
      hyperpolarization and constrained apoptosis.
AB  - Recent studies have shown the mitochondria and mitochondrial DNA are altered in
      gliomas, studied either as primary tissues or in culture. Few studies have been
      performed which evaluate the mitochondria during the development of glial
      malignancy. We used an ethyl-nitrosourea (ENU) in vitro model to assess the
      changes in mitochondrial parameters with progression to astrocyte transformation.
      When compared to the untreated control cells mitochondrial mass of the ENU
      treated cells significantly decreased ontologically early with concurrent
      increase in mitochondrial membrane potential, resulting in hyperpolarization of
      the mitochondrial membrane. At successive divisions, the degree of spontaneous
      apoptosis during astrocyte transformation was significantly diminished in the ENU
      treated cells. With 24 h pre- and co-treatment of ENU cells with citrate, an
      allosteric inhibitor of phosphofructokinase, the astrocytes still became
      immortal, but did not manifest any of the mitochondrial changes nor acquire the
      transformed properties of the ENU treated cells without the inhibition. Indeed,
      the degree of apoptosis noted in these dually treated cells was increased,
      associated with a loss of anchorage independence and low density growth.
      Transformed subclones exposed to citrate after the development of malignant
      properties also exhibited increased apoptosis, and did not form colonies in low
      density plating conditions. These results suggest that the development of
      transformed properties in an ENU model is associated with marked
      hyperpolarization of mitochondrial membrane potential and diminished spontaneous
      apoptosis. Exposure to citrate attenuated these mitochondrial changes and in
      vitro growth properties, with increases in apoptosis. The development of
      transformed astrocytes involve constraints on apoptosis related to alterations in
      mitochondrial membrane potential and mass.

PMID- 14634287
TI  - The biological response of MCF7 breast cancer cells to proteosome inhibition or
      gamma-radiation is unrelated to the level of p53 induction.
AB  - The p53 tumour suppressor is stabilised following exposure to genotoxic agents,
      such as gamma-radiation. Cell responses to p53 stabilisation include induction of
      apoptosis and/or cell cycle arrest. Several studies have suggested that gamma
      radiation stabilises p53 by blocking ubiquitin mediated proteolysis. Here we have
      compared the biological activities of p53 stabilized following exposure to gamma
      radiation or treatment with the proteosome inhibitor N-acetyl-leucinyl-leucinyl
      norleucinal (ALLN) in MCF7 cells with wild type p53. Stabilisation of p53 by ALLN
      was reversible and was not blocked by caffeine. Although ALLN was a more
      effective p53 stabilising agent than gamma-radiation, ALLN was not as effective
      at inducing cell cycle arrest/apoptosis as gamma-radiation. Although p53
      stabilised by ALLN and gamma-radiation were both able to bind DNA and activate
      transcription, ALLN did not increase expression of BAX, which is involved in p53
      induced apoptosis. Therefore, p53 stabilised by different agents is not always
      biologically active to the same extent and additional alterations triggered by
      gamma-radiation may enable p53 to activate a subset of critical target genes,
      such as BAX, which are required for p53 responses.

PMID- 14634288
TI  - Induction and alternative splicing of the Bax gene mediated by p53 in a
      transformed endothelial cell line.
AB  - Overexpression of the normal p53 protein in tumor cell lines is known to induce
      apoptosis and a potential mediator of this response is the apoptotic inducer,
      Bax. The expression of Bax mRNA products were investigated in the ECV-304
      endothelial cell tumor line and primary human umbilical vein endothelial cells
      (HUVEC) that were induced to overexpress the p53 protein. Induction of p53 in ECV
      304 and HUVEC cells was mediated by infection with a p53 recombinant adenovirus
      (AdCMV-p53). The expression of Bax transcripts in p53-induced cells was
      investigated by reverse-transcription polymerase chain reaction (RT-PCR). The Bax
      alpha mRNA species was detected in both ECV-304 and HUVEC cells. Surprisingly,
      Bax alpha expression was reduced several-fold in ECV-304 endothelial cells
      overproducing p53 and no change in Bax alpha was detected in HUVEC cells after
      induction of p53. However, the Bax delta spliced transcript was observed to be
      induced by p53 in the ECV-304 tumor cell line. Bax alpha was the predominant
      species expressed in normal human endothelial cells but, in contrast to the
      immortalized ECV-304 endothelial cell line, induction of p53 failed to alter the
      expression of Bax alpha or to induce any other Bax transcripts. HUVEC cells were
      more resistant to p53, since at least 80% of the HUVEC cell population survived
      the overexpression of p53 after 24 h of infection with AdCMV-p53. An ECV-304
      derived cell line (DECV) resistant to p53-mediated apoptosis did not show any
      changes in expression of Bax mRNA products, even in the presence of high levels
      of p53. ECV-304 endothelial cells that expressed the Bax delta species underwent
      apoptosis much more rapidly and more extensively after induction of p53,
      suggesting that the Bax delta species enhances p53-mediated apoptosis.

PMID- 14634289
TI  - The role of radiation-induced apoptosis as a determinant of tumor responses to
      radiation therapy.
AB  - Ionizing radiation is an effective means of killing tumor cells. Approximately
      50% of all American cancer patients are treated with radiotherapy at some time
      during the course of their disease, making radiation one of the most widely used
      cytotoxic therapies. Currently, much effort is focused on understanding the
      molecular pathways that regulate tumor cell survival following radiotherapy, with
      the long term goal of developing novel therapeutic strategies for specifically
      sensitizing tumors to radiation. At present, there is particular interest in the
      role of tumor cell apoptotic potential as a regulator of both intrinsic and
      extrinsic determinants of the response of tumors to radiation therapy. Here we
      review what is currently known about the role of apoptosis as a mechanism of
      tumor cell killing by ionizing radiation and the relative contribution of
      apoptosis to cellular radiosensitivity and the ability to control human cancers
      using radiotherapy. The following topics will be discussed: (1) radiation-induced
      apoptosis in normal and malignant cells, (2) clinical findings with respect to
      apoptosis in human cancers treated with radiotherapy, (3) the contribution of
      apoptosis to intrinsic radiosensitivity in vitro, (4) the relevance of apoptosis
      to treatment outcome in experimental tumor models in vivo and (5) the potential
      of exploiting apoptosis as a means to improve the therapeutic efficacy of
      radiotherapy.

PMID- 14634290
TI  - Apoptosis in human atherosclerotic plaques.
AB  - Intimal cell death has been a recognized feature of advanced atherosclerotic
      disease. With the advent of DNA in situ end labelling and/or ultrastructural
      techniques, recent findings suggest that cells of an atheroma undergo programmed
      cell death or apoptosis. The pathophysiologic relevance of apoptosis in
      atherosclerotic disease is debatable. Apoptotic cell death may influence lesion
      progression and thus reduce overall plaque burden. Alternatively, apoptosis may
      prove a means of quenching the inflammation, converting cellular-rich lesions to
      so-called 'stable' fibrous hypocellular plaques or conversely weaken the fibrous
      cap causing plaque rupture, a major cause of acute coronary syndromes. Apoptotic
      cells within plaques are typically macrophages, smooth muscle cells and T-cells
      and the frequency of death varies in the different regions of the lesion. The
      precise signalling pathways of apoptosis in plaques are unknown. There is
      however, some evidence that production of immune cytokines may promote apoptosis
      through activation of the Fas ligand-mediated death pathway. Genetic signals that
      regulate apoptosis in the atheroma, at least in smooth muscle cells, may involve
      the tumour suppressor genes p105RB and p53. Further studies as to the relevance
      of apoptosis in acute coronary syndromes and potential mechanisms are emerging.

PMID- 14634291
TI  - CD14 and apoptosis.
AB  - In addition to its role as a mediator of innate pro-inflammatory responses
      following bacterial lipopolysaccharide (LPS) binding, the 55kDa glycosyl
      phosphatidylinositol-linked macrophage plasma membrane glycoprotein CD14 is now
      also known to play a role in phagocytic clearance of apoptotic cells. Although
      apoptotic cell-associated ligand(s) for CD14 await definition, initial findings
      suggest that ligand binding occurs close to, or at the same site as, LPS binding.
      Significantly, in contrast to LPS clearance and in keeping with the non
      phlogistic nature of apoptosis, CD14-dependent engulfment of apoptotic cells
      fails to elicit pro-inflammatory cytokine release from macrophages. Therefore
      CD14 may be regarded as an innate immune receptor both for microbial products-
      after binding which activates inflammatory responses--and for self components,
      which either fail to induce, or alternatively actively suppress, inflammatory
      responses. Here we review current knowledge of the structure and functions of
      CD14, its ligands, its possible modes of signal transduction and its place in the
      panoply of macrophage molecules implicated in apoptotic-cell clearance.

PMID- 14634292
TI  - The role of retinoblastoma protein in apoptosis.
AB  - The retinoblastoma gene and its protein product (Rb) have been studied
      intensively for their role in development, oncogenesis, cell growth,
      differentiation and cell cycle regulation. In addition, Rb appears to be a key
      factor in protecting cells from apoptosis. It is likely that Rb plays an
      essential role in cell survival by regulating the activity of multiple apoptotic
      mediators. Rb expression as a nuclear phosphoprotein is essential for normal cell
      cycle function. Clearly, any damage to the cell cycle or to DNA integrity is a
      potent trigger of apoptosis and Rb involvement. The E2F transcription factor is a
      critical component in the Rb-dependent apoptotic pathway(s), and can act either
      in concert or independently of the p53 tumour suppressor. Until recently, it was
      suggested that Rb, E2F and p53 modulate the apoptotic threshold by acting
      upstream of certain death proteases involved in programmed cell death. However,
      Rb activity can also be regulated downstream by the interleukin-converting enzyme
      like (ICE-like) proteases, which abolish Rb activity by cleavage of aspartate
      enriched regions within its C-terminus. Finally, Bcl-2, which inhibits multiple
      factorial-induced apoptosis, does so, in part, by modulating the phosphorylation
      state of Rb. Taken together, Rb acts not only as a tumour suppressor protein
      which controls cell cycle function, but also determines the final destiny of a
      cell through apoptosis.

PMID- 14634293
TI  - Expression of transcription factor c-Rel and apoptosis occurrence in
      polydactylous and syndactylous limb buds of the talpid3 mutant chick embryo.
AB  - The chicken proto-oncogene c-rel encodes a transcription factor of the Rel/NF
      kappa B family. We have previously shown that c-rel mRNAs accumulate in different
      types of apoptotic cells of the chick embryo, especially in mesenchymal cells
      within the four cell death areas of the limb bud: the anterior and posterior
      necrotic zones, the opaque patch and the interdigital necrotic zones. This study
      aimed to further establish the involvement of c-Rel in apoptosis of the
      developing limb by investigating its expression in the talpid3 mutant which was
      originally shown to be defective in apoptosis. However, our preliminary
      examinations highlighted the apparent presence of apoptotic cells in talpid3
      embryos. Hence, we performed a systematic study of the occurrence of apoptosis in
      mutant and control embryos by the TUNEL method. The results revealed that
      apoptosis does occur in talpid3 embryos but with altered spatial and temporal
      patterns. This suggests that the talpid3 mutation does not affect a gene involved
      in apoptosis per se but rather in the determination of the pattern of apoptosis.
      Neither the expression of c-Rel nor that of its I kappa B alpha inhibitor are
      grossly modified in talpid3 limb buds, suggesting that the talpid3 mutation does
      not affect any of these genes. They are mostly expressed in epidermal, endodermal
      and striated muscle cells in control and in talpid3 limb buds as well. C-Rel was
      also detected in some scarce mesenchymal cells that could be apoptotic, in both
      control and mutant embryos. The only slight difference between control and
      talpid3 limbs lies in the perichondrium which is not fully differentiated in
      talpid3 embryos: c-Rel and I kappa B alpha are only faintly expressed in talpid3
      perichondrial cells, whereas they are both detected in control perichondrial
      cells. Taken together, these results suggest that c-Rel could participate in
      several developmental processes, especially in the differentiation of
      perichondrial cells, besides its already documented involvement in apoptosis and
      haematopoeisis.

PMID- 14634294
TI  - P53-independent caspase-mediated apoptosis in human leukaemic cells is induced by
      a DNA minor groove binder with antineoplastic activity.
AB  - Treatment of HL60 and Jurkat leukaemic cell lines, both not expressing p53, with
      the new non-covalent DNA minor groove binder alpha-bromoacryloyl-distamycin (PNU
      151807), induces apoptosis as shown either morphologically or by DNA laddering
      formation. We evaluated the p53-independent mechanisms of activation of apoptosis
      in these cell systems, by determining the levels of different caspases at
      different times after treatment with PNU 151807. Through Western blotting
      analysis we could measure the cleavage of the 110 Kd form of PARP in both HL60
      and Jurkat cells and correspondingly the activation of CPP32-caspase 3. The
      levels of caspase-1 did not change at any time after drug treatment. By using the
      tetrapeptidic sequence recognized by caspase-3 (DEVD-AMC) or by caspase-1 (YVAD
      AMC) linked to fluorogenic substrate, we also demonstrated that only the DEVD
      sequence was recognized and cleaved after drug treatment, while no significant
      changes were found for YVAD peptides. PNU 151807-induced DNA fragmentation and
      DEVD-cleavage were both inhibited by concomitant treatment with the specific
      inhibitor DEVD-CHO, but not by YVAD-CHO, clearly demonstrating the direct
      activation of caspase-3-like caspases in the induction of programmed cell death
      in these cell lines after minor groove binder exposure.

PMID- 14634295
TI  - Tau protein is involved in the apoptotic process induced by anti-microtubule
      agents on neuroblastoma cells.
AB  - Paclitaxel and docetaxel are potent anti-microtubule and antimitotic agents that
      induce apoptosis in bone marrow-derived cells and epithelial cells. This study
      examined apoptosis induced by anti-microtubule agents in the neuroblastoma SK-N
      SH cell line with a special focus on tau protein which is one of the main
      Microtubule-Associated- Proteins (MAPs) in neuronal cells. In time, treatment
      with 1 microM paclitaxel successively induced formation of bundles, then pseudo
      asters concomitantly with mitotic block and phosphorylation of bcl-2 (48 h), then
      phosphorylation of tau and externalization of phosphatidylserine at the early
      phase of apoptosis (72 h) and finally DNA fragmentation (96 h). Similar results
      were obtained with 0.5 microM vinorelbine. Paclitaxel induced a lower increase in
      tau phosphorylation in differentiated SK-N-SH/RA+ cells which are less sensitive
      to apoptosis. Moreover, doxorubicin whose mechanism of action is independent of
      microtubules also induced immunostaining of tau at 72 h treatment. In conclusion,
      our results on neuroblastoma cells show that overexpression of
      hyperphosphorylated tau is involved in the apoptotic process induced by anti
      microtubule agents and may be extended to others cytostatic drugs. Thus, tau
      protein may play a role in the cellular events observed in neuroblastoma cells
      undergoing apoptosis.

PMID- 14634296
TI  - Different cell cycle mechanisms between UV-induced and X-ray-induced apoptosis in
      WiDr colorectal carcinoma cells.
AB  - Although DNA-damaging agents such as ultraviolet (UV) and X-ray can induce
      apoptosis, the difference in the apoptotic mechanism is not clearly understood.
      In the present study, we investigated the effects of these two genotoxic agents
      on the induction of DNA damage and subsequent apoptotic cell death from the
      viewpoint of cell cycle regulation by using WiDr cells. Transient G1 arrest was
      observed after UV exposure, whereas G2 but not G1 arrest was induced after X-ray
      irradiation. UV-exposure could induce G1 arrest in both mutant-type (mt-p53) and
      wild-type p53 (wt-p53) cells, but obvious G1 arrest was not observed in the cells
      lacking in p53 expression. An increase in the DNA fragmentation was observed at S
      phase in UV-irradiated cells and at G2 phase in X-irradiated cells, respectively.
      UV-irradiated cells showed an increase production of p53 protein and accumulation
      of p21 protein. On the contrary, both p53 and p21 proteins remained at a low
      level in X-irradiated cells. Treatment with aphidicolin, an S phase blocking
      agent, prolonged cell cycle arrest and reduced the rate of apoptotic cell death
      in both UV-irradiated and X-irradiated cells. From these results, it is suggested
      that UV-induced apoptosis occurs mainly at S phase and is regulated by increased
      production of p53 and p21 proteins, while X-ray-induced apoptosis occurs after G2
      blockade and may be independent of p53.

PMID- 14634297
TI  - The gambling self-efficacy questionnaire: an initial psychometric evaluation.
AB  - Instruments to assess individuals' self-efficacy for the control of addictive
      behaviors have been useful for monitoring behavior change, predicting maintenance
      of treatment gains, and identifying potential relapse situations. The Gambling
      Self-Efficacy Questionnaire (GSEQ) was developed to assess perceived self
      efficacy to control gambling behavior. A demographically diverse sample of 309
      adult gamblers completed an initial set of 42 items, of which 16 were selected to
      form the final version of the GSEQ. The GSEQ showed high internal consistency
      (alpha =.96) and good test-retest reliability (r =.86). A factor analysis
      provided some support for a unitary factor structure. As expected, GSEQ scores
      were negatively correlated with reports of problematic gambling behavior.
      Participants experiencing problems related to their gambling behavior scored
      significantly lower on the GSEQ than those who were not experiencing gambling
      problems. This psychometric examination of the GSEQ supported its potential
      utility for treatment planning and outcome evaluation with problem gamblers.

PMID- 14634298
TI  - Definition and measurement of chasing in off-course betting and gaming machine
      play.
AB  - The attempt to recover gambling losses by continuing to gamble ('chasing') has
      featured prominently in accounts of excessive gambling. This research represents
      the first attempt to operationalize and measure chasing in terms of its cognitive
      (behavioral intention), emotive (urges) and behavioral components, and to
      investigate the role of chasing in relation to impaired control over gambling.
      Two survey samples of 84 male off-course (betting shop) race gamblers (mean age
      41, SD = 15) and 137 gaming machine players (73 females, mean age 48, SD = 15 and
      64 males, mean age 43, SD = 16) were recruited at gambling venues. Respondents
      completed a structured questionnaire that investigated retrospective report of
      chasing and an impaired control scale ("The Scale of Gambling Choices"). It was
      found that the various components of chasing formed a composite measure with high
      internal reliability that was strongly related to indicators of excessive
      gambling (e.g. time spent gambling, expenditure as a proportion of income) and to
      impaired control scores. Reacting to large wins by further betting was almost as
      strongly related to impaired control as was persistence after losing. Those who
      returned later to chase had significantly higher impaired control scores than
      those who only chased within a session. Alcohol-related chasing was associated
      with impaired control over gambling. Chasing of losses and impaired control
      appear to be generic processes in evidence across both forms of gambling and
      gender (most format and sex differences were of minor significance).

PMID- 14634299
TI  - A new instrument to measure cognitive distortions in video lottery terminal
      users: the Informational Biases Scale (IBS).
AB  - This paper reports on the development of a new scale, the Informational Biases
      Scale (IBS), to measure cognitive distortions such as the illusion of control,
      gambler's fallacy,illusory correlations, and the availability heuristic in video
      lottery terminal (VLT) players. Ninety-six VLT players recruited from bars in New
      Brunswick took part in the study. Their average (lifetime) South Oaks Gambling
      Screen score was in the probable pathological gambler range. The 25-item IBS was
      shown to have good internal consistency reliability. An exploratory principal
      components/factor analysis revealed the variability of the IBS to be accounted
      for by mainly one factor. The construct validity of the instrument was supported
      by the finding that IBS scores were uniquely determined by measures of gambling
      addiction and negative affect. The IBS should prove useful in both research and
      clinical settings involving VLT gamblers.

PMID- 14634300
TI  - Prevalence rates of youth gambling problems: are the current rates inflated?
AB  - While there is a general consensus in the literature that it is common for youth
      to gamble, considerable variability in the reported prevalence rates of youth
      problem gambling has been found. More recently, issues concerning the possible
      overestimation of these rates have been raised. Arguments underlying the
      proposition that problem gambling rates for youth are inflated are examined. It
      is acknowledged that more rigorous research is required, including the need for
      the development and refinement of current adolescent instruments and screening
      tools, agreement upon a gold standard criterion for adolescent problem gambling,
      and clarity of nomenclature issues. The advancement of scientific knowledge
      concerning the underlying risk factors associated with the onset and course of
      youth gambling involvement and the role of effective adolescent prevention and
      treatment programs will require these fundamental research questions to be
      addressed.

PMID- 14634301
TI  - DSM-IV-J criteria: a scoring error that may be modifying the estimates of
      pathological gambling among youths.
AB  - Previous studies have shown that prevalence rates among youths may be inflated
      due to a problem in understanding the questions of the SOGS-RA and DSM-IV-MR-J.
      This article reports another reason why prevalence rates of pathological gambling
      among youths may be inflated. In 1992, Fisher proposed 9 criteria (the DSM-IV-J)
      for diagnosing pathological gambling among youths, and formulated 12 questions
      (the Test questions) to identify the presence of these criteria. An analysis of a
      sample of studies using the DSM-IV-J reveals that some researchers have
      incorrectly used the 12 Test questions instead of the 9 criteria, which may have
      led to overestimated prevalence rates among youths. Other measurement issues may
      also be contributing to the overestimation of problem gambling in young people.
      The methodological implications of these issues are discussed.

PMID- 14634302
TI  - Near wins prolong gambling on a video lottery terminal.
AB  - The purpose of the present study was to evaluate whether near wins can prolong
      gambling activity on a video lottery terminal. In a three-reel game, near wins
      were operationally defined as two identical symbols followed by a third different
      symbol. Players in an experimental condition were exposed to 27% near wins in a
      series of continuous losses, whereas players in a control group were exposed to
      none. Participants played as long as they wished, and received real money for
      their wins. The results showed that players in the near win condition played 33%
      more games than did the control group. The results of this study suggest that
      near wins can be added to the list of factors that may motivate people to gamble
      despite the probability of monetary loss.

PMID- 14634303
TI  - Problem gambling and comorbid psychiatric and substance use disorders among drug
      users recruited from drug treatment and community settings.
AB  - Little is known about gambling rates of drug users recruited from drug treatment
      compared with those recruited from the community. We use the Diagnostic Interview
      Schedule (DIS) to provide lifetime prevalence estimates of problem gambling
      (i.e., at least one gambling problem) and DSM-III-R pathological gambling (i.e.,
      at least four gambling problems) and describe the association between gambling
      and psychiatric disorders for drug users recruited from drug treatment settings
      (n = 512) and from the community (n = 478). We also report the relative risk of
      being a recreational and problem gambler in this sample. The sample was first
      interviewed in 1989-90 as a part of two NIDA-funded St. Louis-based studies. The
      prevalence of problem gambling in the overall sample was 22% and the prevalence
      of pathological gambling was 11%. There were no statistically significant
      differences in problem and pathological gambling rates for subjects recruited
      from drug treatment and those recruited from the community. The conditional
      prevalence rates, that is, the rate of problem and pathological gambling only
      among gamblers were 27% and 13.5%, respectively. Major findings indicate that
      problem gambling was associated with Antisocial Personality Disorder (ASPD), even
      after controlling for recruitment source and socio-demographic characteristics.
      In fact, when examining the temporal order of these disorders, we found that
      pathological gambling was always secondary to ASPD, occurring on average 11.4
      years after the onset of ASPD. Problem gamblers, compared with everyone else,
      were more likely to be male, African-American, recruited from drug treatment,
      have ASPD and be dependent on illicit drugs. Multinomial logistic regression
      analysis predicted the relative risk of being a recreational and problem gambler
      (compared with a nongambler) in this sample according to socio-demographics,
      ASPD, and dependence on illicit drugs. Results imply that screening for gambling
      problems will need to be broad-based among drug users.

PMID- 14634304
TI  - A comparison of depression and styles of coping in male and female GA members and
      controls.
AB  - Depression and maladaptive coping styles are important components of theories of
      pathological gambling and are frequently foci of treatment with individuals with
      gambling problems. The present study aimed to improve understanding and treatment
      of pathological gambling by comparing levels of depression and styles of coping
      in male and female members of Gamblers Anonymous (GA) to a group of non
      pathological gambling controls matched according to gender, age, education, and
      income. Pathological gambling was measured by the South Oaks Gambling Scale,
      depression by the Beck Depression Inventory, and coping styles by the Problem
      Focused Styles of Coping inventory. Results showed that GA members reported
      significantly higher levels of depression and more maladaptive styles of coping
      than controls. Pathological gamblers' greater use of maladaptive coping was
      evident even when variance attributable to depression was removed, suggesting
      that their coping deficits may be pervasive. Female subjects reported
      significantly greater levels of depression and maladaptive coping than their male
      counterparts. Implications for treating depression and coping styles in
      pathological gamblers are discussed.

PMID- 14634305
TI  - Late life gambling: the attitudes and behaviors of older adults.
AB  - For a significant number of retired older adults (aged 65+), gambling has become
      a new form of recreation and entertainment. While prevalence studies have
      examined the incidence of problem gambling in other age groups, little research
      attention has been paid to the impact of gambling on older adults since the
      increase in availability and accessibility of legalized gambling within the last
      ten years. This study investigated the prevalence of problem gambling behaviors
      (SOGS-R), depression (GDS-15), levels of life satisfaction (SWLS), and
      motivations for gambling among older adults. A total of 315 older adults
      completed the study questionnaire and were grouped and analyzed according to
      those sampled from gambling venues and those from within the community. Results
      of the study found the most frequent accession and spending on several types of
      gambling occurred among older adults who were sampled at gambling venues. Older
      adults who were sampled at gambling venues were also found more likely to have
      higher levels of disordered gambling than older adults from the community, as
      measured by the SOGS-R. Relaxation, boredom, passing time, and getting away for
      the day were also the most likely reported motivations for the older adults who
      were gambling patrons. These findings provide an initial profile of older adults
      and their attitudes, motivations and gambling behaviors.

PMID- 14634306
TI  - Females' coping styles and control over poker machine gambling.
AB  - An investigation of the relationship between impaired control over gambling,
      coping strategies, and demographic variables was conducted by surveying female
      poker machine players (N = 163) in their gaming venues. Metropolitan (n = 14) and
      regional (n = 6) gaming venues in Victoria, Australia participated. Control over
      gambling was measured using the Impaired Control Over Gambling Scale (Baron &
      Dickerson, 1994). Coping strategies were measured using (Folkman et al., 1986)
      adaptation of the Revised Ways of Coping Checklist (Vitaliano et al., 1985).
      MANOVA supported the hypothesis that the lower the control over gambling the
      greater the reliance on emotion-focused coping (blamed self, wishful thinking,
      avoidance) with F = 9.92, 13.35, 14.04 respectively, all significant at p <.001.
      MANOVA failed to supported the hypothesis that problem-focused strategies
      (problem focus, seek social support) would be significantly related to control
      over gambling with F =.82 and.21 respectively. Control over gambling was not
      related to age, employment, relationship status, education, or distress from
      significant life events, further supporting the relationship between control and
      coping strategies. Ways in which coping styles might be related to pathological
      gambling are discussed.

PMID- 14634307
TI  - Perceptions of the extent of problem gambling within new casino communities.
AB  - Several recent studies using objective measures have found that the rate of
      pathological gambling in the U.S. is less than 5%. To determine the general
      population's perception of the prevalence of pathological gambling, a survey was
      conducted in seven communities where casinos have recently opened. Of the 1631
      respondents who provided an estimate, the mean response was that 16% of the
      community residents were problem gamblers, more than three times the rate found
      by studies using specific diagnostic criteria. A regression equation found
      several demographic and attitudinal items are associated with higher prevalence
      estimates. In addition, the data support a "close to home" hypothesis that
      respondents who have relatives who have experienced problems with gambling will
      tend to perceive higher rates of problem gambling in the community.

PMID- 14634308
TI  - Analysis of a casino's self-exclusion program.
AB  - As gambling facilities become more available, the number of pathological gamblers
      increases. Effective therapeutic and preventive interventions should be developed
      and systematically evaluated. Self-exclusion programs may be a useful means to
      facilitate self-control among problem gamblers. This paper describes the
      characteristics of individuals who decided to bar themselves from a Canadian
      casino. Two hundred twenty individuals participated in the present study and
      completed a questionnaire including four sections: (1) socio-demographic data,
      (2) the South Oaks Gambling Screen, (3) gambling habits, and (4) prior
      experiences with the self-exclusion program. According to the SOGS, 95% of the
      participants were classified as severe pathological gamblers on the SOGS (Mean
      score = 9.87). Furthermore, based on self-reported observation, 30% of the
      participants completely stopped gambling once enrolled in this program. No one
      scored within the interval of non-problem gamblers. Suggestions to improve self
      exclusion programs are discussed.

PMID- 14634309
TI  - Trends in bio-behavioral gambling studies research: quantifying citations.
AB  - Both the National Gambling Impact Study Commission and the National Academy of
      Sciences have evaluated the current state of gambling studies research in general
      while making specific suggestions for future efforts in the psychological and
      biomedical areas in particular. Recognizing the importance of evaluating the
      state of the field on a macro level, this paper considers and categorizes several
      decades of psychological and biomedical gambling research. By examining the
      number of references to gambling in two major bibliographic databases,
      quantifiable trends and observations are presented about gambling-related
      psychological and biomedical research. Two trends in particular are salient: the
      rate at which gambling-related articles are published in scholarly journals is
      increasing, and the plurality of these articles deals with issues of cognition
      and personality as related to gambling.

PMID- 14634310
TI  - Juvenile gambling in North America: an analysis of long term trends and future
      prospects.
AB  - Long term trends, based on findings from twenty independent prevalence studies
      surveying middle and high school youth in North America, suggest that within the
      past year two out of three legally underage youth have gambled for money. In the
      United States and Canada as many as 15.3 million 12-17 year olds have been
      gambling with or without adult awareness or approval, and 2.2 million of these
      are experiencing serious gambling-related problems. Lottery play dominates
      legalized forms of gambling among juveniles in both the United States and Canada.
      Trends between 1984-1999 indicate a substantial increase in the proportion of
      juveniles who report gambling within the past year, and a parallel increase in
      the proportion of juveniles reporting serious gambling-related problems. Yet,
      there continues to be little public awareness or concern about the extent, or the
      potential hazards associated with juvenile gambling. A composite profile of
      juveniles reporting numerous gambling problems is contrasted with their peers who
      reported few or none. Future prospects concerning this growing problem are
      offered.

PMID- 14634311
TI  - Gambling and correlates of gambling among Minnesota public school students.
AB  - This study examines the prevalence of gambling and measures the relationships
      between gambling behavior and a number of demographic, psychosocial, and
      behavioral variables among Minnesota public school students. The sample includes
      78,582 male and female Minnesota public school students enrolled in the 9th and
      12th grades. Students were administered the 1998 Minnesota Student Survey, a 121
      item, anonymous, self-administered, paper-and-pencil questionnaire that inquires
      about multiple health-related content domains, including gambling behavior. The
      majority of students were found to have gambled at least once during the past
      year, however, most students did not report gambling frequently, nor did they
      report problems associated with their gambling. Boys reported gambling more often
      than girls, and older students gambled more often than younger students. A larger
      percentage of Mexican/Latin American, African American, American Indian, and
      mixed race students gambled at weekly and daily rates than Asian American and
      Caucasian students. Variables associated with gambling frequency included
      antisocial behavior, gender (being a male), alcohol and tobacco use, age, feeling
      bad about the amount of money they bet, a desire to stop gambling, and increased
      sexual activity. Gambling appears to be related to other risk-taking behaviors
      and may be a part of the adolescent experimentation with adult behaviors.

PMID- 14634312
TI  - Gambling involvement and drug use among adolescents.
AB  - The literature on youth gambling often notes the relationship of gambling
      involvement to drug use. The extent of this association and its importance toward
      advancing knowledge about the origins and course of adolescent gambling are
      discussed. The authors contend that (a) adolescent gambling, like drug use, may
      be a normal part of adolescence from a statistical perspective, (b) claims that
      the prevalence rate of problem/pathological gambling is comparable or higher than
      the rate of substance use disorders are not supportable at this time given the
      weaker methodological studies in the gambling area, (c) while research suggests
      that similar risk factors may be important determinants for both behavior
      domains, prospective studies of adolescent development are needed to further
      clarify which factors are unique and common to adolescent gambling, and (d)
      greater documentation of the harm associated with adolescent gambling is a major
      barrier to garnering more prevention and treatment resources for this issue.

PMID- 14634313
TI  - Risk factors in adolescence: the case of gambling, videogame playing, and the
      internet.
AB  - It has been noted that adolescents may be more susceptible to pathological
      gambling. Not only is it usually illegal, but it appears to be related to high
      levels of problem gambling and other delinquent activities such as illicit drug
      taking and alcohol abuse. This paper examines risk factors not only in adolescent
      gambling but also in videogame playing (which shares many similarities with
      gambling). There appear to be three main forms of adolescent gambling that have
      been widely researched. Adolescent gambling activities and general risk factors
      in adolescent gambling are provided. As well, the influence of technology on
      adolescents in the form of both videogames and the Internet are examined. It is
      argued that technologically advanced forms of gambling may be highly appealing to
      adolescents.

PMID- 14634314
TI  - Prevalence estimates of adolescent gambling: a comparison of the SOGS-RA, DSM-IV
      J, and the GA 20 questions.
AB  - Concerns over the rising prevalence of adolescent gambling problems have become
      more commonplace. A recent meta analysis of studies examining adolescent
      prevalence rates by Shaffer and Hall (1996) has suggested that between 77-83% of
      adolescents are engaging in some form of gambling behavior with between 9.9% and
      14.2% of youth remaining at risk for a serious gambling problem. Their results
      further suggest that between 4.4% and 7.4% of adolescents exhibit serious adverse
      gambling related problems and/or pathological gambling behavior. Comparisons of
      studies are often difficult due to the use of alternative measures, differing
      classification schemes, and nomenclature. The present study examined the gambling
      behaviors of 980 adolescents who were administered three screening measures used
      with adolescents; the SOGS-RA, DSM-IV-J, and the GA 20 Questions. The DSM-IV-J
      was found to be the most conservative measure identifying 3.4% of the population
      as problem/pathological gamblers while the SOGS-GA identified 5.3% and the GA 20
      Questions identified 6% of youth as experiencing serious gambling problems. The
      degree of concordance amongst the measures, gender differences, and
      classification systems are discussed.

PMID- 14634315
TI  - Developing the DSM-IV-DSM-IV criteria to identify adolescent problem gambling in
      non-clinical populations.
AB  - This paper presents a revised version of DSM-IV-J criteria for youth, the DSM-IV
      MR-J, together with psychometric data stemming from its use in a major prevalence
      study of adolescent gambling and problem gambling. The case is made for further
      development and testing of current and emerging instruments to screen for problem
      gambling in youth, with the aim of establishing one internationally accepted gold
      standard measure.

PMID- 14634316
TI  - The South Oaks Gambling Screen Revised for Adolescents (SOGS-RA): further
      psychometric findings from a community sample.
AB  - The broad expansion of gambling across North America during the last two decades
      has generated concern about the extent of gambling and problem gambling in youth,
      and the need to more accurately monitor it. The South Oaks Gambling Screen
      Revised for Adolescents (SOGS-RA) is a promising instrument for screening problem
      gambling (Winters, Stinchfield, & Fulkerson, 1993) that requires more evaluation.
      Accordingly, further psychometric analysis of the instrument was conducted as
      part of a community survey of gambling in a sample of 1,000 male and female
      youth, aged 12 to 17 years. The analyses extended previous focus by including
      females, young adolescents, and an evaluation of youth classified as "at-risk."
      Consistent with preliminary findings obtained during scale development, the
      distribution of item endorsement revealed trends of over-endorsement for some
      items (e.g., gambled more than intended, felt bad about the amount bet), and
      under-endorsement for others (e.g., criticized or told you had a gambling
      problem). These results suggest consideration of some form of weighting
      procedure, item deletion or re-wording. A factor analysis of the SOGS-RA items
      suggested a two-factor solution, with one factor interpreted as Control over
      Gambling and the other Gambling Consequences. It is proposed that the two factors
      may represent early versus more severe levels of gambling problems, respectively.
      The results highlight the need for further psychometric evaluation and refinement
      of instruments used to identify gambling problems in young people.

PMID- 14634317
TI  - On a roll: the process of initiation and cessation of problem gambling among
      adolescents.
AB  - As gambling becomes more accessible and acceptable in society, problems
      associated with gambling and gaming have begun to affect ever increasing numbers
      of adolescents. Although restricted from most forms of gambling by law, many
      adolescents are finding a path into problem gambling. Some are becoming
      compulsive gamblers early in their gambling career, facing a future filled with
      consequences and problems. Understanding the pathway or process by which these
      adolescents become engaged in gambling behavior and how they can extricate
      themselves from this addictive behavior can enhance the efficiency and
      effectiveness of our interventions. This article offers a perspective on the
      initiation and cessation of compulsive gambling using the basic elements of the
      process of intentional behavior change outlined in the Stages of Change from the
      Transtheoretical Model. The process of initiation of a problematic behavior is
      similar to the process of modification or cessation of a problematic behavior in
      terms of these stages of change. With adolescents it is important to distinguish
      between the process of initiation, which has implications for prevention of
      gambling problems, and the process of cessation, which often necessitates the
      assistance of treatment. Creating interventions that parallel the process of
      change offers the potential for personalizing and potentiating efforts to reduce
      the prevalence and consequences associated with compulsive or pathological and
      problem gambling. Application of this model to gambling behavior offers a
      heuristic that is intriguing and requires substantiation through rigorous
      research.

PMID- 14634318
TI  - Adolescents with gambling problems: from research to treatment.
AB  - Considerable interest in the area of youth gambling has prompted an increase in
      empirical investigations examining the correlates associated with youth
      experiencing severe gambling problems. Based upon the current state of knowledge
      and our clinical experience, the development of the treatment program for youth
      with serious gambling problems employed at the McGill University Youth Gambling
      Research and Treatment Clinic is described. The major tenets, underlying
      philosophy, and therapeutic processes are presented. A case study is included to
      illustrate the therapeutic approach. The authors present the need for greater
      funding for more basic and applied research and the necessity for further
      scientifically validated treatment and prevention programs.

PMID- 14634319
TI  - Is the SOGS an accurate measure of pathological gambling among children,
      adolescents and adults?
AB  - The South Oaks Gambling Screen (SOGS) is widely used to assess the prevalence of
      pathological gambling. For a variety of reasons, this instrument may not provide
      an accurate rate of the prevalence of pathological gambling. In this paper, one
      source of error in data provided by the SOGS is investigated. It is argued that
      individuals may not fully understand the meaning of some items, and that
      clarification of the meaning of misunderstood items may in some cases lead to a
      changed score on the scale. The present study evaluates respondents'
      understanding of the SOGS items. The results from three studies are reported,
      each using a different sample: grade school children, adolescents and adults. It
      was hypothesised that (1) participants would not understand some items of the
      SOGS, (2) problem gamblers and probable pathological gamblers would be more
      inclined to interpret items incorrectly than would non-problem gamblers and, (3)
      consistent with the first two hypotheses, clarification of items would decrease
      the number of participants identified as problem gamblers or probable
      pathological gamblers. The data obtained supported hypotheses 1 and 3.
      Furthermore, hypothesis 2 was supported for grade school children, but not for
      adolescents or adults. These results are consistent with recent literature on
      endorsement and acquiescence phenomena, and have implications for prevalence
      studies of probable pathological gambling.

PMID- 14634320
TI  - Measuring the prevalence of sector-specific problem gambling: a study of casino
      patrons.
AB  - This study is the first attempt to measure the prevalence of problem gambling
      attributable to a specific sector of the gambling industry. One thousand, one
      hundred and five casino patrons in 40 casinos in the UK were interviewed, face-to
      face. Respondents were screened for problem gambling using a multiple response
      version of DSM-IV (DSM-IV-MR). The study found support for Eadington's (1988)
      hypothesis, that UK casinos could be largely sustained by regular players, among
      whom the prevalence of problem gambling is high. The study also found support for
      the hypothesis that, to the extent different gambling sectors are patronised by
      demographically different client groups, so the problem gamblers associated with
      them will reflect these client groups. The problem gamblers among the regular
      casino patrons were demographically distinct from the problem gamblers in the
      sample who showed a preference for other gambling forms. Other key findings
      support those found in other jurisdictions. Sector-specific prevalence studies
      may be the next step forward in epidemiological research on problem gambling.
      They have the major advantage of netting significantly more problem gamblers from
      much smaller samples than similar studies in the general population. They also
      have the potential to reveal the proportion of problem gamblers attributable to
      each sector, along with their demographic characteristics. Such information would
      result in more specific information being available for regulators seeking to
      minimise the social impact of problem gambling and those involved in the
      development of prevention and treatment strategies.

PMID- 14634321
TI  - Problem gambling among adolescent students in the atlantic provinces of Canada.
AB  - The objectives of the present study were to determine the prevalence of problem
      gambling among adolescent students in the Atlantic provinces of Canada, and to
      determine the role of age and deception about legal age status as potential risk
      factors for problem gambling. In 1998, a total of 13,549 students in grades 7, 9,
      10 and 12 in the public school systems of the four Atlantic provinces completed a
      self-reported anonymous questionnaire that included the South Oaks Gambling
      Screen-Revised for Adolescents. About 8.2% and 6.4% of adolescent students met
      the broad definition of at-risk and problem gambling, respectively. About 3.8%
      and 2.2% of adolescent students met the narrow definition of at-risk and problem
      gambling, respectively. The prevalence of problem gambling did not vary according
      to age. Using a fake identification or lying about one's age was found to be an
      independent risk factor for problem gambling. Playing video gambling machines was
      the gambling activity associated with the single greatest independent risk of
      using a fake identification or lying about one's age. It was concluded that
      deception about legal age status may be a facilitating factor permitting
      adolescents to gamble to the point of experiencing problems.

PMID- 14634322
TI  - Scratchcard gambling among adolescent males.
AB  - Playing instant scratchcards has become a popular activity among a significant
      minority of the UK population since their introduction by the National Lottery
      operators (Camelot) on March 21, 1995. This study examined scratchcard gambling
      in a group of adolescent males. A total of 204 boys from two secondary schools in
      Birmingham (aged 11 to 16 years; mean age 13.6 years) were administered a
      questionnaire on their scratchcard gambling behaviour. Ten classes (five in each
      school) took part in the survey with one class from each year group selected at
      random by the headteacher. Within each class almost all the children took part.
      Forty-two percent of the sample (n=86) had bought their own scratchcards since
      their introduction in March 1995. Ten children (12% of the gamblers who had
      bought scratchcards themselves) met an adapted version of the DSM-IV criteria for
      pathological gambling on scratchcards. Furthermore, a significant relationship
      was found between parents buying scratchcards and the child's scratchcard
      purchasing behaviour.

PMID- 14634323
TI  - Awareness of gambling-related problems, policies and educational programs among
      high school and college administrators.
AB  - This brief report summarizes a survey of high school and college representatives
      and their awareness toward gambling-related problems. The Massachusetts Council
      on Compulsive Gambling developed a survey instrument to review the policies and
      training programs of 20 high schools and 10 colleges that were located within the
      catchment areas of Massachusetts Department of Public Health state-sponsored
      gambling treatment programs. The results revealed that there is an important
      discrepancy between the prevalence of gambling-related problems among young
      people and the awareness of these problems among educators. High school and
      colleges evidence a paucity of existing gambling-related regulations or policies.
      There is little opportunity for students and educators to learn within the school
      setting about gambling and its potential hazards. Without sufficient in-service
      education and training for faculty and staff, there is little likelihood that
      this group of educators can engage in the early identification or prevention
      efforts that are so vital to advancing the health and welfare of young people.

PMID- 14634324
TI  - Does a brochure about pathological gambling provide new information?
AB  - The purpose of the present study is to evaluate whether a brochure on
      pathological gambling provides new information and knowledge to the general
      population. A total of 115 randomly chosen people from shopping malls and
      municipal parks were randomly distributed to control and experimental groups.
      Results indicated that the brochure provided new information concerning problem
      gambling, at risk behaviors, and the availability of specialised help.

PMID- 14634325
TI  - Airway epithelium and apoptosis.
AB  - Recent advances revealed that airway epithelium possesses versatile functions and
      plays a vital role in the mucosal defense and inflammatory responses. A
      maintenance of airway epithelium integrity is thus important and appears to be
      tightly regulated by a balanced cell proliferation and apoptosis. However,
      homeostasis of airway epithelium is likely affected by multiple environmental
      pathogens, irritants (reactive oxygen species, allergens, etc.), and toxins that
      may lead to various lung diseases. This review briefly summarizes airway
      epithelium apoptosis/proliferation in physiologic and pathological conditions
      along with various factors influencing airway epithelium homeostasis.

PMID- 14634326
TI  - Signalling steps in apoptosis by ether lipids.
AB  - We have investigated the mechanisms of induction of apoptosis by the
      antineoplastic ether lipid ET-18-OCH3 (ALP) in sensitive S49wt mouse lymphoma
      cells and ALP-resistant S49ar variants, both with wild-type p53, and in related
      L1210 cells with mutated p53. Ether lipid-resistant S49ar cells were cross
      resistant to extracellular stress factors (cold shock, heat shock, H2O2,
      dimethylsulfoxide) and to radiation-induced apoptosis but not to physiological
      apoptotic signals (dexamethasone, growth factor deprivation, thapsigargin, C2
      ceramide) and expressed similar levels of the apoptosis-regulating proteins Bcl
      2, Bcl-X, Bax, Bad and Bak as did the parent S49wt cells. The uptake of [3H]-ALP
      was strongly reduced in the stress-resistant cells but this was not associated
      with significant differences in membrane cholesterol:phospholipid content nor in
      membrane microviscosity. In S49ar cells the activity of the antioxidant enzyme
      glutathione peroxidase (GSH-Px) was increased 4-fold and depletion of glutathione
      with the drug L-buthionine-S-R-sulfoximine (L-BSO) lowered the resistance of
      S49ar cells to ALP, stress factors and ionising radiation. The results indicate
      that ether lipids induce apoptosis by imposing a special form of physico-chemical
      stress, mediated by reactive oxygen species but independent of p53 status. The
      capacity of glutathione-dependent anti-oxidant defence appeared an important and
      shared determinant of the sensitivity to ether lipids, several types of
      extracellular stress and ionising radiation.

PMID- 14634327
TI  - Apoptotic cell death and related gene expression in metastatic tumors of AKR
      lymphomas of varying malignancy.
AB  - Resistance to apoptosis may be related to tumor progression, due to the
      implications it might have on both tumor mass and genetic instability. We
      compared the tendency to spontaneous apoptosis and the proliferative capacity of
      metastatic growths of several AKR lymphoma variants (TAU-45, TAU-47, TAU-44, TAU
      33, TAU-42 and TAU-46, in the order of increasing metastatic potential). We
      further compared the expression of several apoptosis-related genes. Cell
      proliferative capacity did not appear to determine malignant behavior since, on
      the whole, a decrease in S + G2M fraction was observed with increasing
      malignancy. Sensitivity to apoptotic cell death decreased with increasing
      malignancy when comparing the TAU-45, TAU-47, TAU-44 and TAU-33 variants,
      suggesting a role of reduced apoptosis in this T-cell lymphoma. An increase in
      Bcl-2 content with increasing aggressiveness among these variants, implicates
      this protein in this tumor progression-related resistance to apoptosis. However,
      the two variants of highest malignancy, TAU-42 and TAU-46, did not follow the
      same trend, since they displayed a relatively high content in apoptotic cells and
      a low Bcl-2 content. Fas receptor expression did not correlate with tendency to
      apoptosis, indicating that malignant behavior in the AKR lymphoma does not depend
      on CD95/Fas/APO1 downregulation. Overexpression of p53 was observed only in one
      of the variants of lowest malignancy.

PMID- 14634328
TI  - Ameloblast apoptosis and IGF-1 receptor expression in the continuously erupting
      rat incisor model.
AB  - Enamel-producing cells (ameloblasts) pass through several phenotypic and
      functional stages during enamel formation. In the transition between secretory
      and maturation stages, about one quarter of the ameloblasts suddenly undergo
      apoptosis. We have studied this phenomenon using the continuously erupting rat
      incisor model. A special feature of this model is that all stages of ameloblast
      differentiation are presented within a single longitudinal section of the
      developing tooth. This permits investigation of the temporal sequence of gene and
      growth factor receptor expression during ameloblast differentiation and
      apoptosis. We describe the light and electron microscopic morphology of
      ameloblast apoptosis and the pattern of insulin-like growth factor-1 receptor
      expression by ameloblasts in the continuously erupting rat incisor model. In the
      developing rat incisor, ameloblast apoptosis is associated with downregulated
      expression of the insulin-like growth factor-1 receptor. These data are
      consistent with the hypothesis that ameloblasts are "hard wired" for apoptosis
      and that insulin-like growth factor-1 receptor expression is required to block
      the default apoptotic pathway. Possible mechanisms of insulin-like growth factor
      1 inhibition of ameloblast apoptosis are presented. The rat incisor model may be
      useful in studies of physiological apoptosis as it presents apoptosis in a
      predictable pattern in adult tissues.

PMID- 14634329
TI  - The effect of caspase-inhibitors on radiation induced apoptosis in human
      peripheral blood lymphocytes: an electron microscopic approach.
AB  - Resting lymphocytes are sensitive to radiation damage and die by apoptosis. We
      investigated the effect of caspase-inhibitors on radiation induced apoptosis in
      human peripheral blood lymphocytes. Lymphocytes were irradiated in vitro with 5
      Gy 60 Co-gamma-rays and cultured for 24 hours in the presence or absence of the
      caspase-inhibitors zVAD-fmk and zDEVD-fmk. Cell death was evaluated by electron
      microscopy. Irradiation in the absence of the inhibitors resulted in about 30%
      dead cells, almost all showing typical apoptotic morphologies. Addition of either
      one of the inhibitors could not rescue cells from death. Part of the dead
      lymphocytes (about 65%) still showed typical nuclear characteristics of apoptotic
      cells: sharply marginated, condensed chromatin, clumped into one sphere or into a
      crescent shaped mass. The remaining part of the dead cells had ultrastructural
      characteristics, aberrant from apoptotic cells: clumping of the chromatin was
      less pronounced and less sharply marginated. Irregular clumps were formed. Data
      indicate that part of the lymphocytes go in apoptosis in a caspase-independent
      way. The other part shows caspase-dependent apoptosis with respect to the nuclear
      events.

PMID- 14634330
TI  - Sequential occurrence of mitochondrial and plasma membrane alterations,
      fluctuations in cellular Ca2+ and pH during initial and later phases of cell
      death.
AB  - The sequential occurrence of plasma and mitochondrial membrane alterations, intra
      cellular pH shifts and changes in intracellular Ca2+ concentration after
      induction of cell death was monitored by flow cytometry in Jurkat and HSB2-cells.
      Cell death was induced by treatment with anti-Fas antibodies or by irradiation.
      Phosphatidylserine (PS) exposure and plasma membrane integrity were measured with
      FITC-Annexin V adhesion and by Propidium Iodide exclusion. Transition of the
      mitochondrial membrane potential was monitored by the occurrence of decay of
      DiOC6 fluorescence. Intracellular pH shifts were monitored by changes in the
      ratio of fluorescence at 575 nm and at 635 nm of SNARF-1-AM. Fluctuations in
      intracellular Ca2+ concentration were established by changes in Fura red
      quenching. The Jurkat cells were sensitive to anti-Fas treatment, while HSB-2
      cells were not. HSB-2 cells appeared more sensitive to radiation damage than
      Jurkat cells. In all experiments the transition of mitochondrial membrane
      potential occurred first, almost immediately followed by PS exposure.
      Fluctuations in intracellular Ca2+ concentration occurred later and were less
      outspoken. A decrease in intracellular pH occurred not earlier than 24 hours
      after anti-Fas treatment. Chelation of intracellular Ca2+ concentration with
      BAPTA-AM had no effect on the time sequence of cell death related events.

PMID- 14634331
TI  - Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with
      bronchial asthma.
AB  - In bronchial asthma, eosinophils are upregulated and their survival is suggested
      to be prolonged by the action of some cytokines such as Interleukin (IL)-3, IL-5
      and granulocyte-macrophage colony-stimulating factor (GM-CSF). We find here that
      the survival of eosinophils in the peripheral blood of patients with asthma is
      correlated with the serum levels of IL-3 but not of IL-5 and GM-CSF.
      Interestingly, theophylline is revealed to induce apoptosis of the prolonged
      survival eosinophils by IL-3, as judged by morphological changes and nucleosomal
      DNA fragmentation. During the apoptosis, caspase-3 in eosinophils stimulated by
      IL-3 is activated by theophylline. The substrate of caspase-3, poly (ADP-ribose)
      polymerase (PARP), is cleaved in the eosinophils after theophylline treatment.
      These results suggest that theophylline is able to induce apoptosis of the IL-3
      activated eosinophils in patients with bronchial asthma, and that its clinical
      effectiveness may be due to the reduction of inflammatory cells in the airway.

PMID- 14634332
TI  - Mimosine induces apoptosis in the HL60 human tumor cell line.
AB  - Mimosine, a plant amino acid not found in proteins, has been widely used as a
      synchronizing agent, blocking the progression of cell cycle on the G1/S phase
      border. The mechanism by which this block is achieved is still unclear. We report
      that in HL60 cells the synchronization is related to an increase in apoptosis.
      Another human tumor cell line, K562, is insensitive to both phenomena thereby
      demonstrating that apoptosis observed in HL60 is line-specific. We hypothesize
      that the mimosine-induced apoptosis and alteration of the cell cycle is due to
      the inhibition of hypusine generation.

PMID- 14634333
TI  - Fas ligand: receptor or ligand?
AB  - In this review, we chronicle the discovery, biochemical characterization, and
      assignment of Fas (CD95) as receptor and Fas Ligand (FasL, CD95L) as ligand. We
      review the functional descriptions of the molecules as death-inducing receptor
      and ligand or as mediators of cell division and/or growth arrest. We suggest that
      bidirectional mediation of signals in receptor-ligand pairs may be a common and
      important mechanism regulating cell fate. Bidirectional signaling clearly impacts
      the interpretation of experimental studies of intercellular communication.

PMID- 14634334
TI  - Apoptin-induced apoptosis: a review.
AB  - Apoptin, a protein encoded by an avian virus, induces apoptosis in various
      cultured human tumorigenic and/ or transformed cell lines, e.g. derived from
      breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma,
      cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent
      apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is
      surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced
      apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is
      unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models
      Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent.
      These data, in continuation with the observations that Apoptin is specifically
      stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by
      Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.

PMID- 14634335
TI  - Identification of an alternative form of caspase-9 in human gastric cancer cell
      lines: a role of a caspase-9 variant in apoptosis resistance.
AB  - Overcoming apoptosis resistance to chemotherapy and radiation may lead to a
      reduction in gastric cancer death. We hypothesize that the apoptotic machinery in
      gastric cancer cells is dependent upon specific cellular conditions. In the
      course of our study of the expression of apoptosis-related genes in human gastric
      cancer cell lines, we have identified a cDNA clone which predicts an alternative
      form of caspase-9. The caspase-9 variant, which we designated as caspase-9 beta,
      retained a truncated structure of native caspase-9 without its catalytic domain
      and was expressed in seven cell lines from human gastric cancer. Among the cell
      lines examined, MKN-28 cells, which exhibited the most resistance against
      apoptotic stimuli, expressed the highest level of caspase-9 beta. The induction
      of apoptosis by staurosporine or actinomycin D was markedly suppressed in caspase
      9 beta-transfected HeLa cells. These results are consistent with our hypothesis
      that the caspase-9 beta may be an endogenous dominant-negative molecule which
      attenuates apoptotic activity in human gastric cancer cells.

PMID- 14634336
TI  - Crosslinking of Fas/CD95 suppresses the CD3-mediated signaling events in Jurkat T
      cells by inhibiting the association of the T-cell receptor zeta chain with src
      protein tyrosine kinases and ZAP70.
AB  - Crosslinking of Fas (APO-1/CD95) on the surface of T cells initiates a
      biochemical cascade leading to programmed cell death. We have previously shown
      that crosslinking of Fas with an apoptosis-inducing IgM anti-Fas mAb results in
      suppression of the CD3-initiated cell signaling including Ca2+ mobilization and
      protein tyrosine phosphorylation. We conducted experiments to decipher the
      mechanisms whereby the cross talk between the Fas- and CD3 signaling pathways
      occur. We used lysates from Jurkat T and examined the composition of the TCR zeta
      chain-precipitated immune complexes using immunoblots. While crosslinking of Fas
      affected the association of p59fyn and p56lck tyrosine kinases with the TCR zeta
      chain to a limited degree, it dramatically inhibited the association of the
      protein tyrosine kinase ZAP70 with the zeta chain. In cells that were
      preincubated with an apoptosis-inducing anti-Fas mAb, the binding of the protein
      tyrosine phosphatases SHP-1 to the TCR zeta chain was increased. These
      experiments indicate that crosslinking of Fas interferes with early T cell
      signaling events by promoting the recruitment of SHP-1 and decreasing the
      association of protein tyrosine kinases with TCR zeta chain. Therefore,
      crosslinking of Fas antigen may regulate the antigen-induced T cell response and
      play an active role in the T cell anergy.

PMID- 14634337
TI  - Role of Ca2+, Mg2+ and K+ ions in determining apoptosis and extent of suppression
      afforded by bcl-2 during hybridoma cell culture.
AB  - We have addressed the possibility that Ca2+, Mg2+ and K+ ions play a central role
      in governing the morphological and biochemical changes attributed to apoptotic
      cell death. By removing Ca2+, Mg2+ or K+ ions from the cell culture medium we
      were able to assess the contribution of each ion to hybridoma cell growth and
      viability. The differences were explained in terms of a possible reduction in
      their respective intracellular levels. From several lines of evidence, the
      deprivation of K+ ions was the most detrimental to cellular growth and viability
      and induced significant levels of early apoptotic cells. Another effect of this
      deprivation was to weaken the plasma membranes without causing membrane
      breakdown; exposure to high agitation rates confirmed fragility of the cell
      membranes. Removal of Mg2+ caused a reduction in the levels of early apoptotic
      cells and predisposed cells to high levels of primary necrotic death. The lower
      levels of apoptotic cells failed to demonstrate the classic nuclear morphology
      associated with apoptosis, while retaining other apoptotic features. These
      results highlighted the importance of utilizing several assays for the
      determination of apoptosis. The absence of Ca2+ appeared to be the mildest
      insult, but its deprivation did accelerate a significant decline in culture by
      increasing apoptotic death. Hybridoma cells overexpressing the apoptotic
      suppressor gene bcl-2 were protected from the predominantly necrosis inducing
      effects of Mg2+ ion deprivation and apoptosis inducing effects of Ca2+ ion
      deprivation. However, apoptosis was not as effectively suppressed in bcl-2 cells
      responding to incubation in K+ free medium. The inclusion of bcl-2 activity in
      the mechanisms of Ca2+ Mg2+ or K+ deprivation induced cell death emphasizes a
      close relationship between ionic dissipation and the apoptotic process.

PMID- 14634338
TI  - Mechanism of apoptosis induced by a lysosomotropic agent, L-Leucyl-L-Leucine
      methyl ester.
AB  - Lysosomes are fundamental for cell growth, and thus inhibition of the lysosomal
      function often leads to cell death. L-Leucyl-L-leucine methyl ester (LeuLeuOMe)
      is a lysosomotropic agent that induces apoptosis of certain immune cells.
      LeuLeuOMe is taken up through receptor-mediated endocytosis, and then converted
      into (LeuLeu)n-OMe (n>3) by dipeptidyl peptidase I (DPPI) in lysosomes, which
      reportedly causes rupture of the lysosomes and DNA fragmentation. In this study
      we examined how lysosomal damage causes DNA fragmentation in LeuLeuOMe-treated HL
      60 cells. When acridine orange was employed to monitor lysosomal membrane
      integrity, orange or red granular fluorescence was seen in normal cells. In
      contrast, LeuLeuOMe-treated cells showed orange, yellow or green cellular
      fluorescence all over the cytoplasm, suggesting that LeuLeuOMe induced a loss of
      lysosomal membrane integrity. The loss was inhibited by a DPPI inhibitor,
      GlyPheCHN2 (GFCHN2), but not by a caspase-3 inhibitor, Ac-DEVD-CHO, indicating
      that a condensation product was responsible for the loss. LeuLeuOMe also induced
      the activation of caspase-3-like protease and DNA fragmentation, both of which
      were inhibited by either GFCHN2 or Ac-DEVD-CHO. Therefore, the activation of
      caspase-3-like protease links the loss of lysosomal membrane integrity to DNA
      fragmentation during apoptosis induced by LeuLeuOMe.

PMID- 14634339
TI  - Induced apoptosis in the prevention of colorectal cancer by non-steroidal anti
      inflammatory drugs.
AB  - Epidemiological, clinical and animal studies indicate non-steroidal anti
      inflammatory drugs (NSAIDs) to be chemopreventive for colorectal cancer. The best
      established target for NSAIDs are the two isoforms of cyclooxygenase (COX), a key
      enzyme in the biosynthesis of prostaglandins. Recent investigations using human
      colorectal tumor cell lines have focused on the cellular and molecular mechanisms
      potentially underlying the chemopreventive effect of NSAIDs. These studies have
      used 'traditional' NSAIDs and their metabolites which either do not inhibit COX,
      are non-selective for the COX isoforms or selectively inhibit COX-1 over COX-2,
      and recently developed NSAIDs that are highly selective for COX-2. In vitro,
      apoptosis is the dominant anti-proliferative effect of each of these classes of
      NSAID and sensitivity to NSAID-induced apoptosis increases with the malignant
      potential of the tumor cells. Limited in vivo evidence backs up these findings.
      Cell cycle arrest also contributes to the in vitro growth inhibitory effect of
      traditional NSAIDs. The induction of apoptosis by NSAIDs may result from the
      inhibition of the COX isoforms but other as yet undefined paths to NSAID-induced
      apoptosis clearly exist. A member of each class of NSAID is under trial as a
      chemopreventive agent for colorectal cancer.

PMID- 14634340
TI  - Nonsteroidal anti-inflammatory drugs and the induction of apoptosis in colon
      cells: evidence for PHS-dependent and PHS-independent mechanisms.
AB  - NSAIDs are potent chemopreventive agents for colon cancer. Although their
      mechanism of action is unknown, it probably relates to their modulation of colon
      epithelial cell kinetics, i.e. apoptosis and/or cell proliferation. NSAIDs are
      pleiotropic in their biochemical activities; their best known effect is
      inhibition of prostaglandin H synthase (PHS), the enzyme catalyzing the
      biosynthesis of prostaglandins. Current data appear to lead to two conflicting
      conclusions. One body of data indicates that PHS is important in induction of
      apoptosis and colon carcinogenesis and that its inhibition by NSAIDs is required
      for induction of apoptosis and their overall chemopreventive effect. Another set
      of data indicates that NSAIDs may induce apoptosis and prevent colon cancer
      without inhibiting the activity of PHS. Both sides of this argument are presented
      and discussed. This apparent contradiction may be resolved if one accepts that
      both mechanisms are correct but that they act on different steps of this
      multistep process.

PMID- 14634341
TI  - Janus faces of ras: anti or pro-apoptotic?
AB  - Cell population homeostasis is a balance between cell proliferation on one hand
      and the rate of cell loss on the other hand. Normal tissue homeostasis requires
      the physiological deletion of cells by activation of apoptosis, a genetically
      determined program of autonomous cell death. ras is most probably the most
      important oncogene in human cancer. It is mutated in 30% of all tumors especially
      those of the gastrointestinal tract. In regulating apoptosis ras has many faces.
      it has both negative and positive effects depending on the stimulation and cell
      type. The responses of cells to ras signaling depends on the level of Ras
      expression, the activity of various pathways, and which of the cell cycle check
      points are functioning. New farnesyl transferase inhibitors and non-steroidal
      anti-inflammatory compounds may provide a new strategy for novel therapeutic
      modalities in the treatment of human cancer. The first clinical trials have been
      initiated, preliminary results are promising, although no firm results are yet
      available.

PMID- 14634342
TI  - Aspirin, NSAIDs and colorectal cancer--what do the epidemiological studies show
      and what do they tell us about the modus operandi?
AB  - A large number of observational epidemiological studies show that regular use of
      aspirin and other NSAID's is associated with a reduction in the risk of
      developing both colorectal adenomas and cancer. Furthermore, the prodrug sulindac
      appears clinically to be able to reduce and reverse the growth of existing polyps
      in familial adenomatous polyposis (FAP). For aspirin and NSAID's the dose,
      duration of effect and length of protection seen after cessation remain to be
      fully established. The available data for aspirin suggest that doses higher than
      those needed for heart disease prevention are required. It is also likely that
      the drug needs to be taken continuously for a number of years. With regards to
      randomised controlled trials to evaluate chemopreventive strategies there are so
      far only limited data available. The only trial reported to date found no effect
      but employed a relatively low dose of 325 mg of aspirin every other day and the
      randomised intervention period was relatively short (5 years). Further trials of
      intermediate endpoints (adenomas) are currently underway in the UK and USA and
      are employing higher doses of aspirin. Randomised clinical studies of sulindac
      have been more encouraging demonstrating that it is a useful drug for therapeutic
      applications in FAP patients. Its relatively greater side effects, however,
      prevent its consideration for primary chemoprevention. The mechanisms by which
      NSAID's act are still sought. Strategies for possible primary and secondary
      chemoprevention in humans also require evaluation.

PMID- 14634343
TI  - NSAIDs and the GI tract-potential hazards and benefits.
AB  - Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have a
      substantial impact upon the gastrointestinal tract with both toxicity and
      benefit. The major toxicity relates to gastroduodenal ulceration and injury to
      the small and large intestine. The major benefits relate to evidence that the
      drugs may prevent, delay or cause regression of progress towards malignancy in
      the colon, and almost certainly also the stomach. The mechanism of toxicity has
      been thought to relate to inhibition of the synthesis of prostaglandins, since
      these are protective to the gastrointestinal mucosa as a result of effects on
      blood flow and mucus and bicarbonate secretion. It is difficult to attribute any
      anti-cancer effect to these actions. Promotion of apoptosis, which appears to be
      independent of prostaglandin synthesis, may better account for both therapeutic
      benefits and possibly some of the toxicity.

PMID- 14634344
TI  - [Clinically important gastroenterologic disorders in Korean elderly].
AB  - Although the function of most organ systems in the body decreases with age, aging
      has relatively little effect on the function of the gastroenterologic organs.
      This is probably due to the large functional reserve capacity, such as redundancy
      in the structure of the organ system and excessive production of hormones and
      enzymes. Most gastroenterologic disorders developed in younger persons may also
      develop in the elderly. However, the presentation, treatment and prognosis may be
      different between elderly patients and younger patients. One important thing is
      the high prevalence of certain disorders in the elderly. For example, the
      incidence of peptic ulcer, ischemic complications of vascular abnormalities, drug
      induced disorders, malignancies, and some other disorders significantly increases
      with age. These disorders results either from age-determined changes in the
      gastroenterologic organs or from extragastroenterologic disorders, such as
      diabetes mellitus, neurologic diseases, and vascular changes. In this paper, an
      important consideration of common gastroenterologic disorders frequently
      developed in the Korean elderly is described. In addition, physiologic and
      pathologic changes of the gastroenterologic organs associated with aging are also
      discussed.

PMID- 14634345
TI  - [Glutathione levels in Helicobacter pylori-infected gastric mucosa].
AB  - BACKGROUND/AIMS: Oxidative stress may contribute to gastric epithelial damage and
      mutagenesis caused by Helicobacter pylori (H. pylori). H. pylori induces
      recruitment and activation of inflammatory cells, which produces reactive oxygen
      species. H. pylori extract directly induces the synthesis of reactive oxygen
      species in gastric epithelial cells and causes DNA damage. The aim of this study
      was to investigate the association between the levels of glutathione (GSH) and H.
      pylori density, histological findings, endoscopic findings, clinical variables,
      and virulence factors. METHODS: Gastric biopsy specimens were obtained from 73
      consecutive patients. The 5,5'-dithiobis-(2-nitrobenzoic acid) reaction was used
      to determine GSH levels. RESULTS: The infection rate of H. pylori was 68.5%. The
      GSH level was not related to age, sex, alcohol intake, and endoscopic findings.
      The GSH level was lower in patients infected with H. pylori. GSH levels were not
      correlated significantly with the grades of neutrophil, intestinal metaplasia,
      and atrophy. However, the GSH levels were significantly correlated with H. pylori
      density (r=-0.296, p=0.01) and monocyte grade (r=-0.257, p=0.02). The GSH levels
      were not related to CagA, VacA, and UreA. CONCLUSIONS: This study suggests that
      H. pylori causes oxidative stresses which deplete GSH in gastric mucosa of
      patients infected with H. pylori.

PMID- 14634346
TI  - [Expression of CD40 in gastric cancer and its effect on the apoptosis of gastric
      cancer cells].
AB  - BACKGROUND/AIMS: The expression of CD40 in gastric cancer has not been studied.
      The aims of this study were to determine the expression of CD40 in gastric cancer
      and to investigate the effect of CD40 on the apoptosis of gastric cancer cells.
      METHODS: We examined the expression of CD40 by immunohistochemistry and flow
      cytometry. CD40 mRNA in 5 gastric cancer cell lines was analyzed by RT-PCR. To
      assess the effect of CD40 on the viability of gastric cancer cells, we performed
      MTT assay. The effect of CD40 signaling on the apoptosis of gastric cancer cells
      was examined by annexin V affinity assay. RESULTS: Twelve of twenty human gastric
      cancer tissues demonstrated positive staining for CD40. Among 5 gastric cancer
      cell lines, AGS cell line expressed membrane-bound CD40 antigen and CD40 mRNA. In
      AGS cells, CD40 stimulation significantly reduced the cell viability. CD40
      ligation significantly increased the apoptosis in AGS cells compared to the
      control. CONCLUSIONS: CD40 is expressed in human gastric cancer tissues and
      gastric cancer cell line, and induces apoptosis in gastric cancer cells. These
      results suggest that CD40 expression in gastric cancer may play an important role
      in host defense mechanism against the gastric cancer.

PMID- 14634347
TI  - [Effects of octreotide on small bowel obstructions in rats].
AB  - BACKGROUNDS/AIMS: Gastrointestinal decompression by nasogastric or intestinal
      tubes developed in 1930s has been the only treatment modality for inoperable
      intestinal obstruction. We hypothesized that the octreotide, a potent inhibitor
      of intestinal secretion, has a therapeutic potential in intestinal obstruction.
      METHODS: Forty Sprague-Dawley rats were randomly assigned to four groups. The
      rats were subjected to complete or partial ileal obstruction. The treated rats
      received octreotide (100 microgram/kg) while the controls received the same
      quantity of saline every 12 hours for 24 or 48 hours. After 24 or 48 hours, the
      volumes of the small bowel contents were measured. The volumes of supernatant and
      the concentrations of electrolytes in the small bowel contents after
      centrifugation were also analyzed. The ileal segments proximal to obstruction
      were harvested, fixed, and stained, and the pathological changes were evaluated
      with mucosal damage scores. RESULTS: There were no statistical differences in the
      volume and the electrolyte composition of intestinal fluid among the 4 groups. In
      the 48 hour complete obstruction group, the octreotide-treated rats showed
      statistically lower mucosal damage scores than the control rats (p<0.05).
      CONCLUSIONS: Octreotide exerts mucosal protecting effect on the complete
      intestinal obstruction rat model.

PMID- 14634348
TI  - [Clinical factors associated with response to biofeedback therapy for patients
      with chronic constipation].
AB  - BACKGROUND/AIMS: Biofeedback therapy has been widely used for the treatment of
      constipated patients. However, there are only a few reports about the clinical
      factors that can predict the effectiveness of biofeedback therapy. The aim of
      this study was to evaluate prognostic factors before the initiation of
      biofeedback treatment in constipated patients. METHODS: Biofeedback treatment was
      performed in 114 patients with constipation. After classifying the patients into
      two groups, responder and non-responder by subjective and objective parameters,
      univariate and multivariate analysis were performed to evaluate the factors
      associated with effectiveness of biofeedback therapy. RESULTS: Eighty-five
      patients (74.6%) responded to biofeedback therapy. Pre-treatment balloon
      expulsion test, paradoxical contraction on manometry, defecation index and anal
      residual pressure during straining were the factors that influenced the results
      of biofeedback treatment. On multivariate analysis, defecation index (odds
      ratio=67.5, p<0.05) and paradoxical contraction on manometry (odds ratio=0.053,
      p<0.05) were the factors that showed significant difference between the
      responders and non-responders. CONCLUSIONS: This study suggests that several pre
      treatment prognostic factors are associated with response to biofeedback for the
      constipated patients. Using prognostic factors, we may be able to evaluate the
      patterns of pelvic floor dysfunction and responsiveness of biofeedback therapy
      for the patients with constipation.

PMID- 14634349
TI  - [Diagnostic role of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic
      autoantibodies in pediatric inflammatory bowel disease].
AB  - BACKGROUND/AIMS: Combined measurement of perinuclear antineutrophil cytoplasmic
      autoantibodies (pANCA) and anti-Saccharomyces cereviseae mannan antibodies (ASCA)
      has recently been suggested as a valuable diagnostic approach to inflammatory
      bowel disease (IBD) in the pediatric age group. The aim of this study was to test
      the accuracy of the assay using pANCA and ASCA in diagnosing pediatric ulcerative
      colitis (UC) and Crohn's disease (CD). METHODS: Sera were collected from 25
      patients with IBD (17 with CD, 8 with UC) and 32 healthy controls. The levels of
      pANCA and ASCA were determined by using a standard indirect immunofluorescence
      technique on ethanol-fixed granulocytes and an ELISA assay, respectively.
      RESULTS: In patients with UC, the sensitivity, specificity, and positive
      predictive value of the pANCA test were 38%, 88%, and 60%, respectively. Such
      values were not changed significantly in the case of positive pANCA and negative
      ASCA. The sensitivity, specificity, and positive predictive value of ASCA test in
      diagnosing CD were 71%, 88%, and 92%, respectively. The combination of pANCA
      negative and ASCA positive was not significant. CONCLUSIONS: ASCA and pANCA
      assays are highly disease specific for CD and UC, respectively. These serological
      tests can assist clinicians in diagnosing and categorizing patients with IBD and
      may be useful in making therapeutic decisions.

PMID- 14634350
TI  - [Predictive factors and efficacy of lamivudine treatment in chronic hepatitis B
      infection].
AB  - BACKGROUND/AIMS: Lamivudine, an oral nucleoside analogue, effectively suppresses
      hepatitis B virus (HBV) replications and improves liver enzymes as well as liver
      histology. The aim of this study was to evaluate the effectiveness of lamivudine
      and the patient-dependent or laboratory variables that predict HBeAg
      seroconversion. METHODS: We retrospectively analyzed 519 consecutive patients
      with HBeAg-positive chronic hepatitis B who were treated with lamivudine. The
      duration of lamivudine therapy was from 6 to 64 months (mean 20 months). RESULTS:
      The HBeAg seroconversion was achieved in 192 patients (37%). The cumulative HBeAg
      seroconversion rates were 28% at 12 months, 39% at 24 months, 49% at 36 months,
      and 53% at 48 months. The predictive factors of lamivudine-induced HBeAg
      seroconvresion were the changing patterns of quantitative HBeAg level during
      lamivudine therapy, pretreatment quantitative HBeAg levels, ALT levels, and the
      duration of lamivudine therapy. One hundred eighty-three patients who had
      achieved HBeAg seroconversion showed patterns that HBeAg levels were continuously
      decreased. Therapy was discontinued after HBeAg seroconversion in 121 patients.
      Sixty-six patients experienced a relapse during the follow-up period (mean 8.9
      months). CONCLUSIONS: The continuously decreasing patterns of quantitative HBeAg
      levels during lamivudine therapy can predict HBeAg seroconversion in clinical
      settings.

PMID- 14634351
TI  - [An analysis of extravariceal collaterals of gastric varices using magnetic
      resonance angiography in portal hypertensive patients].
AB  - BACKGROUND/AIMS: This study was aimed to analyze the relationship between gastric
      varices and its collaterals using magnetic resonance angiography (MRA) and to
      assess the usefulness of MRA in studies of portosystemic circulation. METHODS:
      Eighty-one patients who had portal hypertension with gastric varices took MRA
      before the therapy for gastric varices. RESULTS: The types of collaterals
      observed by MRA were left gastric vein in 67 patients (83%), short gastric vein
      in 28 (35%), gastrorenal shunt in 25 (31%), and splenorenal shunt in 14 (17%). In
      most of patients with advanced gastric varices, the size of left gastric vein was
      larger than others. In most cases of large gastric varices, the short gastric
      vein ranged between 5 to 10 mm. Gastrorenal shunt was also correlated with the
      size of gastric varices. The types of more prominent esophageal varices showed a
      right type (left gastric vein predominance), but the types of more prominent
      gastric varices or only the gastric varices showed a left type (posterior or
      short gastric vein predominance) (p<0.05). CONCLUSIONS: Gadolinium enhanced 3D
      MRA can contribute to the study of the hemodynamic relationships between gastric
      vein and the collateral circulations by presenting more clear images for patients
      with portal hypertension.

PMID- 14634352
TI  - [Clinical features of hepatocellular carcinoma in the 1990s].
AB  - BACKGROUND/AIMS: There has been a shift of the etiologies of chronic liver
      disease in the 1990s. Therefore, we studied clinical characteristics of
      hepatocellular carcinoma (HCC) in the 90s. METHODS: Medical records of 806
      patients diagnosed as having primary HCC were reviewed. Etiology, clinical and
      laboratory characteristics were evaluated according to the time of diagnosis (the
      early period, 1992-1995; the late period, 1996-2000). RESULTS: The mean age was
      55.7 years and male to female ratio was 4.6:1. The proportion of the symptomatic
      patients at the time of diagnosis was decreased from 67.4% of the early period to
      41.3% of the late period. On the other hand, that of the patients detected by a
      periodic check-up was increased up to 58.7% in the late period from 32.6% in the
      early period (p<0.01). The majority of the patients accompanied cirrhosis (73.3%)
      and the main cause of HCC was HBV (78.6%) with no changes in the etiologic
      distribution according to the periods. The proportion of the candidates for
      surgical resection was significantly increased to 12.4% in the late period
      compared with 7.1% in the early period. CONCLUSIONS: Although the proportion of
      HCC which can be treated curatively has increased in the later half of the 1990s,
      its absolute number is still small. More meticulous periodic examination may be
      required in high risk patients.

PMID- 14634353
TI  - [Expression of MUC3, MUC5AC, MUC6 and epidermal growth factor receptor in
      gallbladder epithelium according to gallstone composition].
AB  - BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the
      gallstone formation. However, there is little information about the diversity of
      mucin secretion according to the stone composition. Epidermal growth factor
      receptor (EGFR) functions in proliferation including mucin secreting goblet cell
      hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB
      epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB
      pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the
      gallstone disease were studied. Stone composition was analyzed by the
      spectrophotometer. Immunohistochemical stain was performed using each monoclonal
      antibody. The percentage of stained proportion was scored by the NIH image
      program and the results were compared between both groups. RESULTS: Total 20
      patients were enrolled (10 patients with cholesterol gallstones, 10 patients with
      pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and
      MUC6 were 42 +/- 27%, 31 +/- 15%, and 17 +/- 9%, respectively in GB-chol group
      and 32 +/- 22%, 33 +/- 23%, and 15 +/- 10%, respectively in GB-pig group
      (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80%
      (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in
      the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies
      are needed to elucidate the role of EGFR in the gallstone formation.

PMID- 14634354
TI  - [A case of inflammatory fibroid polyp presenting with jejunal bleeding].
AB  - Inflammatory fibroid polyp occurs very rarely in the jejunum and gastrointestinal
      bleeding as an initial manifestation of inflammatory fibroid polyp has not been
      reported. We report a case of a jejunal inflammatory fibroid polyp presenting
      with melena for 10 days. Upper gastrointestinal endoscopic examination was
      negative for any active bleeding lesions and abdominal angiography failed to
      localize the bleeding site as well. In contrast, computed tomography of the
      abdomen demonstrated a segmental wall thickening of the jejunum with a tumor-like
      mass lesion associated with dense contrast enhancement. Consistent with this,
      technetium 99m red blood cells scintigraphy exhibited red cell pooling at the
      right upper quadrant. On exploratory laparotomy, there was an active bleeding
      from the site of the jejunal tumor and a segmental resection was performed.
      Histologically, the tumor lesion of the jejunum was consistent with inflammatory
      fibroid polyp. Thus, we conclude that the tumor lesion was a cause of the
      gastrointestinal bleeding.

PMID- 14634355
TI  - [Two cases of systemic amyloidosis presenting with abnormalities in liver
      function tests].
AB  - Systemic amyloidosis results from the deposition of insoluble, fibrous amyloid
      proteins. It occurs mainly in the extracellular spaces of multiple organs and
      tissues including the kidney, heart, and liver. Although amyloid deposition in
      the liver is common in patients with systemic amyloidosis, clinically apparent
      liver disease is relatively rare. Indeed, most patients with systemic amyloidosis
      manifest only minimal to moderate hepatomegaly and trivial abnormalities in liver
      function tests. Recently, we experienced two cases of patients who presented with
      abnormalities in liver function tests and hepatomegaly as manifestations of
      systemic amyloidosis. We report these cases with a review of the relevant
      literatures.

PMID- 14634356
TI  - [A case of common bile duct stone formed around a surgical clip after
      laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy has now rapidly replaced open cholecystectomy.
      Rarely a calculus may arise from a metallic surgical clip migrated into the
      common bile duct (CBD) after this surgical procedure was performed. We report a
      50-year-old man with CBD stone formed around a surgical clip, who had undergone a
      laparoscopic cholecystectomy because of acute calculous cholecystitis 14 months
      before. Abdominal CT revealed a single stone in mildly dilated CBD. A high
      density core within the CBD stone, was suspected to be a surgical clip. The stone
      was removed using a retrieval balloon catheter and basket after endoscopic
      sphincterotomy.

PMID- 14634357
TI  - [A case of common bile duct stone developed due to a surgical clip as a nidus: an
      experience of successful management by endoscopy].
AB  - Surgical clips can migrate into the biliary tract and act as a nidus for stone
      formation. We report a case of common bile duct stone developed due to a surgical
      clip in a 48-year-old man. Endoscopic retrograde cholangiogram revealed a common
      bile duct stone a with metallic clip in it. He had laparoscopic cholecystectomy
      10 years ago. The stone was removed endoscopically. The use of resorbable clips
      during laparoscopic cholecystectomy is recommended to avoid this type of
      complication.

PMID- 14634358
TI  - Prediction of discharge status of persons with brain injury in rehabilitation.
AB  - The present study sought to identify the factors as well as what would predict
      discharge of persons with brain injury. Demographics (age, pre-injury educational
      level, pre-injury occupational status) and Disability Rating Scale (DRS) scores
      during admission and upon discharge were used for discharge status prediction. A
      multiple discriminant analysis (MDA) revealed that the DRS scores at admission
      and upon discharge were significant predictors that correctly classified 72% of
      grouped cases.

PMID- 14634359
TI  - Early community outreach intervention in children with acquired brain injury.
AB  - Ten patients with acquired brain injury were recruited over an 18 month period in
      the south-western health care region of Sweden in order to evaluate the costs and
      effectiveness of a multidisciplinary community outreach intervention programme.
      An experienced multidisciplinary project team was involved and patients underwent
      detailed functional, cognitive and motor assessments following initial contact
      within two weeks of injury, within six weeks of injury and at a 12-month follow
      up. An individualized counselling programme was also offered. Of an expected
      recruitment number of 50 patients (based on epidemiological and population based
      figures) 10 children were reached, evaluated and followed; eight patients with
      traumatic brain injury (five severe, two moderate and one mild), and two patients
      with non-traumatic brain injury (both severe). At follow-up there was a
      significant improvement in motor function. No significant changes were seen in
      other areas of functional assessment or on neuropsychological measures although
      there were mild improvements in communication and behaviour functions. The
      financial costs per patient in the programme were deemed relatively modest
      compared with cost estimates of shorter-term in-patient rehabilitation. Time
      intensive interventions included supporting caregivers and school staff and the
      direct and indirect patient interventions were shown to enhance support and
      promote active involvement of local services.

PMID- 14634360
TI  - The use of a modified Delphi procedure for the determination of 26 prognostic
      factors in the sub-acute stage of stroke.
AB  - The aim of this study was to reach consensus about the prognostic factors when
      deciding the discharge destination from a hospital stroke unit, and to construct
      a prognostic conceptual framework. To realise an optimal integration of knowledge
      from research findings and from clinical experience by expert opinions we used a
      'modified Delphi Technique', which is the most commonly used method for the
      production of clinical guidelines. The process yielded 26 prognostic factors,
      which were arranged in clinical and social sub-domains. The sub-domains and the
      factors within each sub-domain were prioritised according to their assumed
      predictive value for the decision process. The order of importance of the
      prognostic factors in the clinical domain was: (1) disabilities, (2) pre-morbid
      disabilities, (3) impairments and (4) disease/biology; and the order of
      importance of the factors in the social domain was: (1) home front, (2) social
      situation and (3) residence. The Delphi procedure is an excellent instrument to
      determine and prioritise prognostic factors. With this procedure research-based
      and consensus-based knowledge can be combined. For a valid procedure it is
      mandatory to state explicitly in advance how the scores will be judged, and to
      explain the scientific level of the evidence during the whole procedure.

PMID- 14634361
TI  - Rehabilitation outcome of Turkish stroke patients: in a team approach setting.
AB  - The aim of this study was to identify the efficacy of in-patient stroke
      rehabilitation, to evaluate the relationship between clinical characteristics and
      functional outcome, and to determine factors predicting functional outcome at
      discharge in Turkish stroke patients with a team approach. Retrospective data
      were collected from 102 of 116 patients with first stroke who were admitted to
      our rehabilitation unit at Ankara University. Demographic data, length of
      hospital stay (LOHS), onset to admission interval (OAI), type, side and location
      of stroke lesion, and most common medical complications were recorded. Functional
      Independence Measure (FIM) and Brunnstrom's motor recovery stages (BMRS) were
      assessed on admission and at discharge. The mean age was 61.6 +/- 10.9 years and
      the mean LOHS was 69.7 +/- 28.2 days. The mean FIM total scores were 69.2 +/-
      27.4 and 83.2 +/- 25.7 on admission, and at discharge, respectively. The mean FIM
      total score was significantly correlated to age, LOHS and motor recovery. The FIM
      total scores of patients with aphasia and depression were found to be lower than
      those of patients without aphasia and depression. In a stepwise multiple
      regression analysis, FIM total score on admission, age and OAI were found to be
      valid predictors of FIM total score at discharge. Functional Independence Measure
      total score on admission was the strongest variable. Our results suggest that
      knowledge of the poor prognostic factors effecting functional outcome on
      admission can provide information to clinicians in identifying severity of
      stroke. Admission FIM total score, can be used to predict the patients'
      functional recovery. Advanced age, aphasia and post-stroke depression contribute
      to lower FIM scores.

PMID- 14634362
TI  - Quality of life for people with physical disabilities: a new instrument.
AB  - This article describes the development and validation of the Quality of Life
      Profile for Adults with Physical Disabilities (QOLP-PD). This new cross
      disability instrument is grounded in a well-developed conceptual framework. It
      reflects the underlying assumption that quality of life issues are the same for
      people with and without disabilities, although adults living with chronic
      physical disabilities may address those issues somewhat differently during the
      course of their daily lives. This instrument was developed on the basis of in
      depth interviews, item review and refinement, and pilot testing with adults who
      have chronic acquired and life-long physical disabilities. Preliminary validation
      studies were carried out in separate studies with two Canadian samples for which
      separate results are reported. In Study 1, interviewer-administered items were
      completed by a cross-disability sample from a large city in Ontario (n = 27). In
      Study 2, self-administered items were completed by adults with spinal cord
      injuries from urban and rural Saskatchewan (n = 40). Alpha coefficients for the
      QOLP-PD ranged from 0.67-0.97 (Ontario sample) and from 0.84-0.98 (Saskatchewan
      sample). Validation coefficients are also reported. Although the samples were
      small, the psychometric properties of the instrument are generally sound. Future
      research directions are discussed.

PMID- 14634363
TI  - Racial identity and cultural mistrust among African-American recipients of
      rehabilitation services: an exploratory study.
AB  - Empirical evidence of how cultural and/or sociopolitical forces may impact the
      world view of an ethnic minority with a disability is integral to improving our
      understanding of the complex interplay among client characteristics, agency
      variables, societal factors and rehabilitation success. The purpose of this study
      was to investigate if there is a difference in the level of racial identity and
      cultural mistrust for African-Americans closed successfully and those closed
      unsuccessfully by a state/federal rehabilitation agency. Significant differences
      in one of four key racial identity levels were found between the two groups
      F(1,140) = 4.58, p < 0.05. However no significant differences on cultural
      mistrust were found between the two groups. There was a moderate positive
      correlation found between age and one of the levels of racial identity (r = 
      0.5947, p < 0.05) and a moderate negative (inverse) relationship between age and
      another level of racial identity (r = -0.5545, p < 0.05). Theoretical and service
      implications of the findings are discussed.

PMID- 14634364
TI  - A review of the management of Guillain-Barre syndrome in a regional neurological
      rehabilitation unit.
AB  - A database search was performed to identify all patients presenting to a
      Rehabilitation Centre over a five-year period with a confirmed diagnosis of
      Guillain-Barre syndrome. Retrospective analysis of acute and rehabilitation
      hospital notes was performed and information on demographics, management and
      outcome obtained. There were equal numbers of males and females with an average
      age of 36 years. 75% had a prodromal illness and 62.5% presented with distal
      paraesthesia. 75% exhibited cranial nerve signs and 62.5% required artificial
      ventilation for a prolonged period. The investigations performed and treatment
      given varied and did not always coincide with current evidence. An aetiological
      agent was identified in 50%. There were a wide variety of complications in the
      acute hospital and the inpatient stay was prolonged in all but 1. There was one
      complication after transfer to the rehabilitation unit and statistical analysis
      of the admission and discharge FIM scores revealed a statistically significant
      improvement in outcome (p = 0.013). There is currently no consensus on the
      management of patients with GBS in the acute setting despite a wide evidence
      base. Many patients are being discharged without access to rehabilitation
      services. Our results suggest that rehabilitation makes a measurable and
      significant difference and should be available to all patients with GBS.

PMID- 14634365
TI  - Strategies to promote activity and participation in children and youths with
      acquired brain injuries.
AB  - Strategies used by hospital and community-based rehabilitation and educational
      professionals and parents for promoting activity performance and participation of
      children and youths with acquired brain injuries (ABI) in the hospital, at home,
      at school and in the community are described in this article. Semi-structured
      interviews with interdisciplinary staff from a pediatric rehabilitation hospital
      in the Northeast USA and focus groups comprised of hospital and community-based
      educational and rehabilitation professionals and parents were conducted.
      Interviews and focus groups were audiotaped, transcribed verbatim and
      qualitatively analyzed. The strategies described fell into three categories:
      Routine, Repetition, and Consistency; Supports and Models; and Curriculum and
      Environmental Modifications. In addition, three broader factors emerged related
      to the use of strategies: Communication; Age, Development and Recovery Time; and
      Attitudes and Expectations. Findings may provide insights to professionals and
      families to promote activity performance and participation in children and youth
      with acquired brain injuries across the continuum of care.

PMID- 14634366
TI  - Base of support feedback in gait rehabilitation.
AB  - The purpose of this study was to investigate the effect of feedback information
      about base of support in gait rehabilitation. Sixteen individuals with
      hemiparesis resulting in narrow base of support, were randomly placed into two
      equal groups, experimental and control. The experimental group was provided with
      a portable device that provided extrinsic auditory feedback information about
      base of support incorporated in the functional context of conventional gait
      therapy, whereas the control group received a conventional gait therapy only.
      Changes in step width with treatment were assessed with step print technique. The
      experimental group of subjects improved their step width with treatment from 0.09
      +/- 0.003 m to 0.16 +/- 0.006 m while individuals assigned to the control group
      showed smaller improvement from 0.099 +/- 0.004 m to 0.13 +/- 0.003 m. While both
      groups demonstrated statistically significant improvement (p < 0.05), the level
      of recovery of step width seen in the experimental group was greater.

PMID- 14634367
TI  - Intra-individual variability of self-esteem in adolescents with spina bifida.
AB  - The purpose of this study was to explore intra-individual variability of global
      self-esteem and physical self-worth in adolescents with spina bifida (n = 3).
      Three adolescents were assessed in their schools by auto-evaluation over a period
      of 12 weeks (three times a week) with the Physical Self Inventory-6, a six-item
      questionnaire with a visual analogue scale. Statistical analyses included auto
      correlation function (ACF) for studying the time series. Descriptive statistics
      demonstrated that in all the dimensions of physical self and global self-esteem,
      participants showed great variability over time. Auto-correlation function
      indicated 20 non-stationary and unstable time series, and four stationary time
      series. The non-stationary evolution of physical self, and global self-esteem in
      the three adolescents with spina bifida studied may explain the absence of
      consensus in the literature on the level of the self-perception. Future
      longitudinal research needs to be engaged.

PMID- 14634368
TI  - Stroke rehabilitation therapy in a patient with a cardiac pacemaker for chronic
      atrial fibrillation.
AB  - A 65-year-old man was implanted with an artificial pacemaker for chronic
      bradycardic atrial fibrillation associated with hypertensive heart disease. Five
      years after the pacemaker implantation, he suffered from a cerebral embolism.
      Approximately 4.5 months after the ictus, he was transferred to the
      rehabilitation ward. He had flaccid left hemiplegia and severe disuse syndrome.
      He could not sit and could tilt his head up for only two minutes because of
      severe orthostatic hypotension. By modulating the rate-responsive mode of the
      pacemaker every 2-4 weeks, we were able to rehabilitate the patient. Thus, the
      patient could sit in a wheelchair for more than three hours. This case emphasizes
      the importance of examining the mode and function of a previously implanted
      artificial pacemaker. In accord with varying rehabilitation programs and gradual
      improvement in a patient's physical activities, periodic modulation of a
      programmable pacemaker can lead to a better functional outcome during
      rehabilitation therapy.

PMID- 14634369
TI  - Intention to apply or accept an alternative job among participants of extended
      employment programs.
AB  - The research studied 249 people employed in extended employment programs in
      northern Israel with respect to their intention to apply for an alternative job
      (an active step) or to accept a new job offer (a passive step). Findings
      indicated that young, single people who were living with their parents and
      perceived their level of disability as mild indicated more intention to apply for
      an alternative job or to accept a new job offer. Furthermore, people with low
      monthly wages, less satisfaction with their income and with the extended
      employment program in general, and a lack of participation in non-employment
      activities expressed a greater inclination to apply for an alternative job or to
      accept a new job offer. The only difference between people's intentions to apply
      for an alternative job (an active step) or to accept a job offer (a passive step)
      was in regard to their perception of their disability. The intention to apply for
      an alternative job was associated with mild disability, whereas the acceptance of
      a new job offer was related to mild and moderate disability.

PMID- 14634370
TI  - Development of job-seeking ability in people with arthritis: evaluation of a
      pilot program.
AB  - Working Horizons is an intervention designed to prevent work disability by
      addressing the internal and external barriers faced by people with arthritis in
      their attempts to enter or maintain their positions in the employment arena. The
      aim of the pilot study was to determine whether Working Horizons influenced
      participants' self-efficacy and psychological well-being and to describe the
      experience of Working Horizons from the perspectives of participants and
      employment advisors (EAs). The study was a pre-test post-test design with an
      Intervention Group (n = 22) and Comparison Control Group (n = 22). Quantitative
      data were collected by self-completed questionnaires at baseline and at six
      months follow-up. Qualitative data were collected via open questions on the
      questionnaires, interviews with a sub-sample of 10 participants, and a focus
      group with EAs at the end of the programme. Pilot data suggested that Working
      Horizons was effective in terms of increasing participants' job-seeking self
      efficacy. In addition, the Intervention Group showed significant improvements on
      self-esteem and satisfaction with life. Qualitative findings confirmed that
      participants felt more 'confident' in relation to seeking employment, were more
      accepting of their condition, felt more positive and had greater awareness of the
      social model of disability. Participants valued the emotional and instrumental
      support provided by the EAs, who acted as successful 'work' role models.
      Interventions, such as Working Horizons, may be an effective means of addressing
      work disability, acting as a gateway to statutory services. The value of suitable
      role models in mentoring capacities was highlighted.

PMID- 14634371
TI  - Counselors' and consumers' derived criteria for assessing the effectiveness of
      rehabilitation services.
AB  - This study surveyed a group of rehabilitation counselors and consumers to obtain
      their consensus regarding alternative measures to assess the effectiveness of
      vocational rehabilitation service interventions. Results suggest that in addition
      to employment outcomes, other factors such as psychological, social, and economic
      well-being should be considered.

PMID- 14634372
TI  - The genetic basis of cancer of the kidney.
AB  - PURPOSE: The types of epithelial renal tumors are clear cell, types I and II
      papillary, chromophobe and oncocytoma. We identified the genetic basis of these
      different types of kidney cancer to provide better methods for early diagnosis of
      this disease as well as provide the foundation for the development of molecular
      therapeutic approaches. MATERIALS AND METHODS: To identify the genetic basis of
      kidney cancer we studied families with an inherited predisposition to kidney
      cancer. Families in which 2 or more individuals had kidney cancer underwent a
      comprehensive evaluation to determine whether they were affected with a
      hereditary form of renal carcinoma. Genetic linkage analysis was performed to
      identify the gene for inherited forms of renal carcinoma. RESULTS: The gene for
      the inherited form of clear cell renal carcinoma associated with von Hippel
      Lindau gene was identified. This gene has been found to be a tumor suppressor
      gene. A new form of inherited renal carcinoma, hereditary papillary renal
      carcinoma, was identified. The gene for this condition was identified and found
      to be the proto-oncogene c-Met. A previously unidentified form of familial renal
      oncocytoma was found. A familial form of chromophobe renal carcinoma and
      oncocytoma associated with Birt Hogg Dube syndrome was found. The gene for this
      condition was localized on the short arm of chromosome 17 and it has been
      identified. We studied families with cutaneous leiomyomas, uterine leiomyomas and
      papillary renal carcinoma. We identified mutations in the fumarate hydratase gene
      in patients affected with this disorder, namely hereditary leiomyoma renal cell
      carcinoma. CONCLUSIONS: Kidney cancer used to be considered a single disease. It
      is now known that there are a number of different types of cancers of the kidney
      with different histological patterns and different clinical courses that appear
      to respond differently to therapy. These different types of kidney cancer are
      caused by different genes, ie they each have a distinct genetic basis.
      Understanding the molecular pathways of these cancer genes should provide insight
      into their varying clinical courses and responses to treatment as well as provide
      the foundation for the development of disease specific molecular therapeutic
      strategies.

PMID- 14634373
TI  - Urologists on a tightrope--do we have a net?
AB  - PURPOSE: The purpose of this review is to analyze the current health care
      environment and its impact on urological practice. MATERIALS AND METHODS: The
      medical and lay literature as it pertains to the socioeconomics of health care
      was reviewed. RESULTS: Analysis of the political and economic factors that
      influence the delivery of health care today reveals alarming realities. More than
      40 million Americans remain uninsured, and with a retrenched economy that number
      is likely to increase. Neither government nor the private sector has been either
      willing or able to address the health care problem in a coherent or comprehensive
      way. As the population ages, the Medicare and Medicaid programs will become
      further stressed. Employers are increasingly unwilling to finance the health care
      expenses of their employees. Academic medical centers are facing unique
      exigencies that, if left uncorrected, will jeopardize the future training of
      physicians. CONCLUSIONS: In the current environment of a depressed economy,
      further proposed tax cuts and increased military spending it appears inevitable
      that the economic restraints on medical care will increase substantially in the
      foreseeable future.

PMID- 14634374
TI  - Serum pro prostate specific antigen improves cancer detection compared to free
      and complexed prostate specific antigen in men with prostate specific antigen 2
      to 4 ng/ml.
AB  - PURPOSE: Pro prostate specific antigen (pPSA) is a precursor form of PSA enriched
      in tumor compared to benign prostate tissues that may be a more specific serum
      marker for prostate cancer. Serum pPSA was measured in the clinically relevant
      early detection PSA range of 2 to 10 ng/ml. MATERIALS AND METHODS: Research use
      immunoassays were used to measure native and truncated forms of pPSA. The subject
      cohort contained 1,091 serum specimens from men enrolled in prostate cancer
      screening studies at 2 sites who had undergone prostate biopsy and were divided
      into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml
      (benign 315, cancer 221). RESULTS: In PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to
      10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer
      specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary
      biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001).
      Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA
      4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for
      % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml
      range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA
      and 9% for complexed PSA (p <0.0001). CONCLUSIONS: The %pPSA significantly
      improved specificity for cancer detection and decreased the number of unnecessary
      biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA
      compared to % free PSA and complexed PSA was maintained throughout the PSA range
      of 2 to 10 ng/ml.

PMID- 14634375
TI  - Endoscopic renal papillary biopsies: a tissue retrieval technique for
      histological studies in patients with nephrolithiasis.
AB  - PURPOSE: The mechanisms behind calcium nephrolithiasis remain unclear. Previous
      research has relied on animal models or cell lines, yielding limited insight into
      the pathophysiology of human calcium stone disease. To determine changes
      occurring in the human kidney during active stone disease we used an endoscopic
      renal papillary biopsy protocol in calcium stone formers undergoing percutaneous
      nephrolithotomy. MATERIALS AND METHODS: Following stone burden clearance via
      percutaneous nephrolithotomy 15 idiopathic calcium oxalate and 4 ileal bypass
      stone formers underwent flexible and rigid nephroscopy. Biopsies from select
      papillae in the peripheral and interpolar regions were obtained with 5Fr flexible
      cup biopsy forceps. A papilla adjacent to the accessed calix was biopsied with
      10Fr cup biopsy forceps. Cortical biopsies along the access tract were also
      obtained with the 10Fr forceps. RESULTS: All patients had successful biopsy
      completion. No complications were attributable to the biopsy process and no blood
      transfusions were required. Of the 19 patients 12 were contacted for followup at
      a mean of 21.7 +/- 9.0 months with none experiencing adverse sequelae such as
      bleeding or significant pain. A total of 14 patients had followup serum
      creatinine available showing that the difference in mean preoperative and
      postoperative values was not clinically significant (1.00 +/- 0.27 and 1.11 +/-
      0.27 mg/dl, respectively). The quality of biopsied tissue permitted accurate
      immunohistochemical staining of crystal deposits and mineral analysis.
      CONCLUSIONS: Endoscopic papillary biopsies were performed safely in a small
      patient population. Tissue obtained using this protocol can be used for detailed
      histological and analytical studies, which may lead to significant advances in
      our understanding of stone formation mechanisms.

PMID- 14634376
TI  - Evaluation of synchronous twin pulse technique for shock wave lithotripsy:
      determination of optimal parameters for in vitro stone fragmentation.
AB  - PURPOSE: The Twinheads extracorporeal shock wave lithotriptor (THSWL) is composed
      of 2 identical shock wave generators and reflectors. One reflector is under the
      table and the other is over the table with a variable angle between the axes of
      the 2 reflectors. The 2 reflectors share a common second focal point, making it
      possible to deliver an almost synchronous twin pulse to the targeted stone. We
      studied the optimal parameters for in vitro stone fragmentation. MATERIALS AND
      METHODS: Two types of 1 cm artificial stones were used, namely Bon(n)-stones of 3
      compositions (75% calcium oxalate monohydrate [COM] plus 25% uric acid, struvite
      and cystine) and plaster of Paris. The parameters tested were shock wave number
      (100, 500 and 1,000), shock wave power (8, 11 and 14 kV) and angle between the
      reflector axes (67, 90 and 105 degrees). After the optimal parameters were
      determined we studied the disintegrative efficacy of THSWL for 3 types of human
      urinary calculi, including COM, calcium hydrogen phosphate (brushite) and
      cystine. Each stone received 1,000 twin shock waves at 14 kV with an angle of 90
      degrees between the reflectors. All experiments were done using a rate of 60 twin
      shock waves per minute. Following lithotripsy stone fragments were processed and
      sized. The ratio of the weight of fragments greater than 2 mm-to-total weight of
      all fragments was calculated. RESULTS: Optimal stone fragmentation results for
      THSWL were obtained with the maximum number of shock waves (1,000) and full power
      (14 kV). There was no significant statistical difference in fragment size or the
      ratio of fragments greater than 2 mm with the use of different angles except for
      cystine and plaster of Paris calculi, for which the right angle was most
      effective. At application of the optimal parameters to human stones THSWL
      produced small fragment size for COM and cystine stones, while brushite stones
      were not fragmented to the same extent. CONCLUSIONS: The efficacy of synchronous
      twin pulse technology improves as the number of shock waves and power increase. A
      90-degree angle between the shock wave reflectors is advantageous for certain
      stones (that is cystine and plaster of Paris) but it is not a factor for other
      stone compositions. THSWL has satisfactory disintegrative efficacy for human
      stones, especially COM and cysteine calculi.

PMID- 14634377
TI  - Serum troponin levels are not increased in patients with ventricular arrhythmias
      during shock wave lithotripsy.
AB  - PURPOSE: Ventricular arrhythmias are common during ungated shock wave
      lithotripsy. We determined whether lithotripsy induced arrhythmias are associated
      with myocardial damage. MATERIALS AND METHODS: A total of 51 patients presenting
      for shock wave lithotripsy for right renal stones were prospectively evaluated
      for arrhythmias during lithotripsy. In patients with arrhythmias troponin levels
      were determined 24 hours after the procedure. RESULTS: Ventricular arrhythmias
      developed in 21 patients. In this group all troponin levels were below the level
      of detection (less than 0.5 ng/ml). CONCLUSIONS: Lithotripsy associated
      arrhythmias do not appear to be associated with myocardial injury.

PMID- 14634378
TI  - Retrograde intrarenal lithotripsy outcome after failure of shock wave
      lithotripsy.
AB  - PURPOSE: We report our experience with retrograde intrarenal lithotripsy (RIRL)
      for renal stones not alleviated by shock wave lithotripsy (SWL). MATERIALS AND
      METHODS: A total of 28 females and 53 males with a mean age of 53 years (range 18
      to 86) were studied. They had been treated with a mean of 3.2 previous SWLs. Mean
      stone size was 9.2 mm (range 4 to 22) and the mean number of stones per patient
      was 1.27 (range 1 to 5) for a total of 103 stones overall. In 70 patients there
      was 1 stone. Rigid and flexible ureteroscopes were used in 8 and 67 cases,
      respectively, while a combined approach was used in 6. A holmium:YAG laser was
      used for fragmentation in 52 patients. Success was defined as stone-free status
      or residual fragments less than 3 mm. RESULTS: The overall success rate was 67%.
      RIRL yielded a 46% stone-free rate. Of the 44 patients 17 (39%) had residual
      stones less than 3 mm, while 13 required ancillary procedures. There were no
      residual ureteral stones. Original stone size correlated inversely with the
      success rate. Most failures involved lower pole stones, in that laser fiber
      deflection prevented reaching them in 9 cases. The procedure was interrupted due
      to extravasation or bleeding in 5 patients and 6 had postoperative urinary tract
      infections (16% overall complication rate). CONCLUSIONS: RIRL effectively and
      safely alleviated upper tract stones unresponsive to earlier SWL. It can be
      considered salvage therapy in such cases. RIRL is well suited for treating stones
      less than 2 cm with better stone-free rates than SWL in the same circumstances.
      Residual stones were more likely in lower pole cases.

PMID- 14634380
TI  - Vesical calculi with unrepaired vesicovaginal fistula: a clinical appraisal of an
      uncommon association.
AB  - PURPOSE: Primary vesical calculi are uncommon in patients with vesicovaginal
      fistula (VVF). We retrospectively analyzed 19 such cases and present our
      experience with the management of this condition. MATERIALS AND METHODS: Between
      January 1989 and December 2002, 19 patients were treated for this association.
      All patients provided a history and underwent physical examination, metabolic
      evaluation for stone disease, urine culture test and cystovaginoscopic
      examination. They were treated with a staged procedure with the fistula repaired
      2 to 3 months after stone removal. RESULTS: VVF was a result of obstructed labor
      in all cases. The patients presented a mean of 28.8 months after fistula
      formation. No metabolic abnormality was detected in any patient. Urine culture
      was positive for Proteus mirabilis in 6 and Escherichia coli in 5, and it yielded
      mixed growth in 8. All women had some residual urine in the bladder (mean 11 ml).
      The fistula was located supratrigonally in 13 cases, while it was high trigonal
      in the remainder. A total of 17 patients were treated endoscopically by
      cystolitholapexy or fragmentation of the stone by transurethral cystolithotripsy
      using a Lithoclast (Microvasive Urology, Natick, Massachusetts). Two patients
      required open suprapubic cystolithotomy. All patients underwent fistula repair 3
      months after stone removal with successful results in 16. CONCLUSIONS: Primary
      vesical calculi in patients with VVF are associated with urinary contamination, a
      high or supratrigonal fistula location, residual urine in the bladder and a long
      history of disease. Staged management of the problem showed good results.

PMID- 14634379
TI  - Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones.
AB  - PURPOSE: We evaluated the efficacy of the alpha1-adrenergic antagonist tamsulosin
      for conservative expulsive therapy in patients with ureteral colic due to
      juxtavesical stones. MATERIALS AND METHODS: A total of 60 consecutive symptomatic
      patients with stones located in the juxtavesical tract of the ureter were
      randomly divided into group 1--30 who received oral floroglucine
      trimetossibenzene 3 times daily and group 2--30 who received 0.4 mg tamsulosin
      daily. The 2 groups received 30 mg deflazacort daily for 10 days plus
      cotrimoxazole 2 times daily for 8 days and 75 mg diclofenac injected
      intramuscularly on demand. Ultrasound followup and medical visits were performed
      weekly for 4 weeks. Stone passage rate and time, analgesic use, hospitalization
      and endoscopical intervention were evaluated. Statistical analysis was performed
      using the Student t test. RESULTS: The stone expulsion rate was 70% for group 1
      and 100% for group 2. Mean stone size was 5.8 and 6.7 mm, respectively (p =
      0.001). Mean expulsion time was 111.1 hours for group 1 and 65.7 hours for group
      2 (p = 0.020). The mean number of diclofenac injections was 2.83 for group 1 and
      0.13 for group 2 (p <0.0001). Ten group 1 patients were hospitalized, of whom 9
      underwent ureteroscopy, compared with none in group 2 (p <0.0001 and 0.001,
      respectively). CONCLUSIONS: Tamsulosin used as a spasmolytic drug during renal
      colic due to juxtavesical calculi increased the stone expulsion rate and
      decreased expulsion time, the need for hospitalization and endoscopic procedures,
      and provided particularly good control of colic pain.

PMID- 14634381
TI  - Predictive factors for applicability and success with endoscopic treatment of
      upper tract urothelial carcinoma.
AB  - PURPOSE: We report on endoscopic treatment outcomes for upper tract urothelial
      carcinoma and identify predictive factors for success. MATERIALS AND METHODS: A
      total of 61 renal units were referred for endoscopic treatment of an upper tract
      tumor, 69% of which did not have a traditional indication for nephron sparing
      approaches. Tumor pathology and operative findings were assessed retrospectively
      for treatment outcomes and influential factors. RESULTS: Initial ureteroscopic
      inspection was undertaken in 53 renal units with resection attempted in 18 (34%)
      resulting in an 89% success rate with 16 treated. A percutaneous approach in 19
      renal units (11 after ureteroscopy) was 100% successful in achieving tumor-free
      status, for a total of 35 renal units successfully treated endoscopically.
      Surveillance then began on 27 renal units with a recurrence rate of 88% and mean
      time to recurrence of 5.8 months (range 2 to 20). Of patients undergoing
      surveillance (31% of whom had high grade disease), 54% remain or have died of
      unrelated disease, during a mean followup of 21.0 months (range 3 to 48). Higher
      tumor grade, larger size, renal pelvis location (all p <0.01) and multifocality
      (p = 0.05) significantly correlated with decreased recurrence-free survival, but
      did not predict failure of local control by endoscopic surveillance. CONCLUSIONS:
      Although endoscopic techniques can render most patients tumor-free, there is a
      high associated recurrence rate and many need repeat procedures. Recurrence-free
      survival is greater in patients with low grade, solitary or less bulky disease.
      However, rigorous surveillance after endoscopic resection can lead to success
      even in patients with high grade, multifocal or large volume disease, resulting
      in preservation of renal units.

PMID- 14634382
TI  - Solid renal tumors: an analysis of pathological features related to tumor size.
AB  - PURPOSE: We examined the relationship between tumor size and malignancy among
      solid renal tumors, and the relationship between tumor size and RCC subtype
      within tumors with renal cell carcinoma (RCC). MATERIALS AND METHODS: We
      identified 2,770 adult patients who underwent radical nephrectomy or nephron
      sparing surgery for sporadic unilateral nonmetastatic solid renal tumors between
      1970 and 2000. All pathology specimens were reviewed by a urological pathologist
      for diagnosis, and in RCC tumors, for histological subtype and nuclear grade.
      RESULTS: There were 376 benign (12.8%) and 2,559 (87.2%) malignant tumors. The
      percentage of benign tumors decreased from 46.3% for those less than 1 cm to 6.3%
      for those 7 cm or greater. Among RCC tumors the percentage that were clear cell
      increased from 25.6% for those less than 1 cm to 83.0% for tumors 7 cm or
      greater, while the percentage that were papillary decreased from 74.4% for those
      less than 1 cm to 10.0% for tumors 7 cm or greater. No RCC tumors less than 1 cm
      were chromophobe compared to 7.0% of tumors 7 cm or greater. The percentage of
      malignant tumors that were high grade RCC increased from 2.3% for those less than
      1 cm to 57.7% for RCC tumors 7 cm or greater. Only 1% of all tumors less than 1
      cm and 9.2% of all tumors less than 2 cm were high grade malignancies.
      CONCLUSIONS: As tumor size increased there was a significant increase in the odds
      of having a malignant compared to a benign tumor, clear cell compared to
      papillary RCC and high grade compared to low grade malignancy.

PMID- 14634383
TI  - Validation of an integrated staging system toward improved prognostication of
      patients with localized renal cell carcinoma in an international population.
AB  - PURPOSE: Outcome prediction for patients with renal cell carcinoma is based on a
      combination of factors. In this study a previously published clinical outcome
      algorithm based on 1997 T stage, Fuhrman grade and performance score is validated
      using an international database. MATERIALS AND METHODS: A total of 1,060 patients
      from Nijmegen, the Netherlands (NN), MD Anderson (MDA) and University of
      California, Los Angeles (UCLA) who had localized renal cell carcinoma were
      evaluated for outcome prediction using a clinical outcome algorithm previously
      shown to stratify patients into low, intermediate and high risk groups.
      Validation was performed by comparing the 3 risk groups separately within the 3
      centers as well as by comparing hazard ratios and concordance indices among the 3
      centers. RESULTS: Estimated disease specific survival rates at 5 years for the
      low risk groups were 94% (NN), 92% (MDA) and 93% (UCLA). The 5-year disease
      specific survival rates for the intermediate risk groups were 65% (NN), 73% (MDA)
      and 78% (UCLA), while the rates for the high risk groups were 40% (NN), 30% (MDA)
      and 48% (UCLA). The concordance indices for each of the databases were 79% (NN),
      86% (MDA) and 84% (UCLA). CONCLUSIONS: A clinical algorithm that uses only 3
      prognostic variables (1997 T stage, Fuhrman grade and performance status) to
      stratify patients with localized renal cell carcinoma into 3 risk groups has been
      shown to be applicable to external databases. This algorithm may be useful for
      patient counseling, surveillance and identification of high risk patients for
      enrollment in clinical trials.

PMID- 14634384
TI  - A multifactorial postoperative surveillance model for patients with surgically
      treated clear cell renal cell carcinoma.
AB  - PURPOSE: We designed scoring algorithms for postoperative surveillance based on
      multivariately significant predictors of site specific disease recurrence.
      MATERIALS AND METHODS: We identified 1,864 patients who underwent partial or
      radical nephrectomy for nonmetastatic clear cell renal cell carcinoma between
      1970 and 2000. Clinical features studied included age, sex and symptomatic
      disease at presentation. Surgical and pathological features studied included
      nephrectomy type, surgical margin status, 2003 TNM stage, nuclear grade,
      histological tumor necrosis, sarcomatoid component, cystic architecture and
      multifocality. Recurrence was classified into locations of abdomen, thoracic
      region, bone and brain. Recurrence-free survival rates were estimated using the
      Kaplan-Meier method. Cox proportional hazards models were fit to test
      associations with recurrence. RESULTS: Recurrence to abdomen, the thoracic
      region, bone and brain developed in 185 (10%), 300 (16%), 134 (7%) and 81 (4%)
      patients, respectively. Positive surgical margins, 2003 TNM stage, size, grade
      and necrosis were significantly associated with abdominal recurrence in a
      multivariate setting. These same features, except surgical margins, were
      significantly associated with thoracic recurrence. The 2003 TNM stage, grade and
      necrosis were multivariately predictive of recurrence in bone. Scoring algorithms
      to predict the likelihood of disease recurrence to these sites and to guide the
      intensity of postoperative surveillance were developed using regression
      coefficients from the multivariate models. The proposed scoring algorithms
      resulted in excellent patient stratification. CONCLUSIONS: We present scoring
      algorithms based on multivariately significant predictors of site specific
      recurrence that can be used to tailor postoperative surveillance to the
      individual patient.

PMID- 14634385
TI  - Renal cell carcinoma--prognostic factors.

PMID- 14634386
TI  - The effects of radio frequency ablation on renal function and blood pressure.
AB  - PURPOSE: Radio frequency ablation (RFA) is evolving as a nephron sparing
      treatment alternative for select patents with small renal tumors. The impact of
      ablated tissue on the remaining kidney parenchyma is unknown. To assess this
      impact we evaluated pretreatment and posttreatment serum creatinine (sCr), and
      blood pressure of patients treated with RFA with at least 6 months of followup.
      MATERIALS AND METHODS: From our series of 69 tumors treated with RFA 25 patients
      with a total of 26 tumors and a minimum 6-month followup were identified. RFA was
      delivered percutaneously or laparoscopically depending on tumor location and
      patient preference. Blood pressure measurements and sCr levels were obtained at
      preoperative and postoperative office visits. Values for preoperative and
      postoperative systolic blood pressure, diastolic pressure and sCr were each
      compared. Estimated creatinine clearance was calculated for each patient before
      and after treatment, and compared. RESULTS: No patient experienced new onset
      hypertension or worsening of existing hypertension. Likewise no changes in mean
      sCr and estimated creatinine clearance were observed. CONCLUSIONS: Treatment with
      RFA does not appear to have an effect on renal function or blood pressure. RFA
      appears to be a medically safe therapy for patients with small renal tumors.

PMID- 14634387
TI  - Preliminary experience using high intensity focused ultrasound for the treatment
      of patients with advanced stage renal malignancy.
AB  - PURPOSE: We present the preliminary results of patients with advanced stage renal
      malignancy treated with high intensity focused ultrasound (HIFU), and investigate
      the safety and feasibility of using HIFU in the treatment of selected patients
      with renal tumors. MATERIALS AND METHODS: HIFU treatment was performed in 12
      patients with advanced stage renal cell carcinoma and 1 patient with colon cancer
      metastasized to kidney. Patients were followed after treatment to observe
      complications and long-term therapeutic efficacy. Complications and changes in
      symptoms seen at presentation were recorded. Mid stream urine specimens were sent
      for microscopy and serum creatinine was measured postoperatively. Followup
      radiological examinations were performed to detect tumor response to the
      ablation. RESULTS: A total of 13 patients received HIFU treatment safely,
      including 10 who had partial ablation and 3 who had complete tumor ablation.
      After HIFU hematuria disappeared in 7 of 8 patients and flank pain of presumed
      malignant origin disappeared in 9 of 10 patients. Postoperative images showed
      decrease in or absence of tumor blood supply in the treated region and
      significant shrinkage of the ablated tumor. Of the 13 patients 7 died (median
      survival 14.1 months, range 2 to 27) and 6 were still alive with median followup
      of 18.5 months (range 10 to 27). CONCLUSIONS: This preliminary experience
      suggests that HIFU could be safe and feasible in the treatment of patients with
      advanced renal malignancy.

PMID- 14634388
TI  - Simultaneous transurethral resection of bladder tumor and benign prostatic
      hyperplasia: hazardous or a safe timesaver?
AB  - PURPOSE: We evaluated the effect of simultaneous transurethral resection of
      bladder tumor (TURBT) and benign prostatic hyperplasia (TURP) on recurrences at
      the bladder neck and prostatic urethra. MATERIAL AND METHODS: During the 10-year
      study period 51 patients fulfilled the entry criteria of past simultaneous TURBT
      and TURP, histologically confirmed transitional cell carcinoma of the bladder and
      benign prostatic hyperplasia, a preserved bladder and a minimal followup of 12
      months. Their records were analyzed retrospectively. Patients were divided into
      28 with single (group 1) and 23 with multiple (group 2) bladder tumors. RESULTS:
      During the 12 to 120 months of followup (mean 37.3) the average tumor recurrence
      rate was 68.6%, that is 53.6% in group 1 and 86.9% in group 2. Recurrences
      appeared within an average of 14.9 months, that is within 18 (range 4 to 36) in
      group 1 and 13.5 (range 3 to 36) in group 2. Tumor recurrence was at the bladder
      neck and/or prostatic urethra in 11 of the 51 cases (21.5%). Average time to
      recurrence at the prostatic fossa was 23.8 months, that is 27 (range 13 to 46) in
      group 1 and 21.6 (range 4 to 60) in group 2. Only 1 patient had a single
      recurrence in the prostatic fossa, while the others also had synchronous and
      metachronous recurrences at other bladder sites. Tumor progression to
      invasiveness was diagnosed in 3 of the 51 patients (5.9%). CONCLUSIONS: Our data
      indicate that simultaneous TURBT and TURP do not negatively affect tumor
      recurrence at the bladder neck and prostatic urethra.

PMID- 14634389
TI  - The addition of urinary urokinase-type plasminogen activator to urinary nuclear
      matrix protein 22 and cytology improves the detection of bladder cancer.
AB  - PURPOSE: We have previously reported that urinary urokinase-type plasminogen
      activator (uPA) and its receptor (uPAR) are elevated in patients with bladder
      cancer. In the current study we tested the hypothesis that urinary uPA and uPAR
      would add to the predictive ability of urinary nuclear matrix protein 22 (NMP22)
      and cytology for the diagnosis of bladder cancer. MATERIALS AND METHODS: Urinary
      uPA, uPAR and NMP22 were measured in voided specimens obtained before cystoscopy
      in 229 consecutive subjects at risk for transitional cell carcinoma (TCC), of
      whom 122 (53%) were found to have bladder TCC. Bladder washout samples for
      cytology were also collected in 191 subjects. Associations with TCC were tested
      by logistic regression. Nonparametric ROC curves were generated and AUCs were
      compared. RESULTS: Urinary uPA, uPAR and NMP22 were higher in patients with TCC
      than in controls (p <0.001, 0.016 and <0.001, respectively), while uPA (test for
      trend p = 0.018) was associated with the risk of TCC after adjusting for NMP22 (p
      = 0.028), urinary cytology (p <0.001), age (p = 0.107) and uPAR (test for trend p
      = 0.756). The overall AUC for determining TCC was not different between uPA and
      NMP22 (0.746 and 0.714, p = 0.092). However, in the high sensitivity region of
      the ROC curve the AUC of uPA was larger than that of NMP22. CONCLUSIONS: Adding
      uPA to NMP22 and cytology improves their ability to predict bladder TCC by a
      statistically and prognostically substantial margin. An approach using multiple
      biomarkers may improve the diagnostic accuracy of voided urinary diagnostic
      tests.

PMID- 14634390
TI  - Preoperative plasma soluble E-cadherin predicts metastases to lymph nodes and
      prognosis in patients undergoing radical cystectomy.
AB  - PURPOSE: We have previously reported that high urinary levels of soluble E
      cadherin (sE-cadherin) are associated with an increased risk of bladder cancer.
      We determined whether plasma levels of sE-cadherin are associated with bladder
      cancer stage and prognosis. MATERIALS AND METHODS: The study group consisted of
      50 patients who underwent radical cystectomy for muscle invasive cancer or
      intravesical therapy refractory Tis, Ta, or T1 bladder cancer; and 40 men without
      cancer. Preoperative plasma levels of sE-cadherin were measured using a
      commercially available enzyme-linked immunosorbent assay kit. RESULTS: Plasma sE
      cadherin was higher in patients with bladder cancer than in healthy subjects (p
      <0.0001) and it was elevated in patients with metastases to regional and distant
      lymph nodes (p = 0.019 and 0.024, respectively). When adjusted for the effects of
      clinical stage and grade, preoperative sE-cadherin was independently associated
      with metastases to regional lymph nodes (p = 0.028) and disease progression (p =
      0.006) but not with bladder cancer mortality. In postoperative models
      preoperative sE-cadherin and lymph node metastases were associated with disease
      progression (p = 0.017 and 0.042, respectively) after adjusting for the effects
      of pathological stage, grade and lymphovascular invasion but only lymph node
      metastases were associated with cancer specific mortality (p = 0.007).
      CONCLUSIONS: Higher plasma sE-cadherin is associated with bladder cancer. Higher
      preoperative plasma sE-cadherin has the potential to identify patients with
      metastases to regional and distant lymph nodes who are at increased risk for
      failure of local therapy with curative intent. These patients may benefit from
      more extensive lymph node dissection and/or combined modality treatment regimens.

PMID- 14634391
TI  - The prognostic significance of metastatic perivesical lymph nodes identified in
      radical cystectomy specimens for transitional cell carcinoma of the bladder.
AB  - PURPOSE: We determined the prognostic significance of metastatic perivesical
      lymph nodes (PVLN) in transitional cell carcinoma of the bladder (TCC). MATERIALS
      AND METHODS: A retrospective review of 198 consecutive patients who underwent
      radical cystectomy for clinically organ confined TCC identified 32 patients with
      PVLN in pathology specimens. Patient characteristics were compared. Overall
      survival, disease-specific survival (DSS) and disease-free survival were
      estimated using Kaplan-Meier actuarial methodology. The log-rank test was used to
      compare the differences between patients with and without metastatic TCC to PVLN.
      Cox multivariate regression analysis was used to determine whether the effect of
      metastatic PVLN on survival was independent of pathological stage. RESULTS:
      Metastatic TCC was found in the PVLN of 14 patients. Median followup and age were
      13.5 months and 66.5 years, respectively. Patients with and without metastatic
      PVLN had similar characteristics and pathological disease staging. The overall
      survival, DSS and disease-free survival were significantly less for patients with
      metastatic TCC in PVLN (p = 0.002, p = 0.013 and p <0.001, respectively), and
      involvement of PVLN and pelvic nodes (p = 0.001, p = 0.010 and p = 0.041,
      respectively). Metastatic PVLN was an independent predictor of OS and DSS (p =
      0.016 and p = 0.025, respectively). CONCLUSIONS: Metastases to PVLN appear to
      confer a significantly worse prognosis for patients undergoing radical
      cystectomy. Patients with identifiable metastatic PVLN may benefit from early
      adjuvant therapies.

PMID- 14634392
TI  - Prostatic zinc and prostate specific antigen: an experimental evaluation of their
      combined diagnostic value.
AB  - PURPOSE: In cancer affected prostate cells lose the ability to concentrate zinc,
      resulting in a substantial decrease in Zn in the prostate. We investigated the
      possibility of using prostatic zinc combined with prostate specific antigen (PSA)
      as a novel tool for the reliable diagnosis of prostate cancer. MATERIALS AND
      METHODS: Using the x-ray fluorescence method the Zn concentration was determined
      in vitro in prostate samples extracted by surgery from 28 patients. Clinical
      records included age, serum PSA, sextant prostate needle biopsy, previous medical
      therapy, surgical procedure and histological findings. RESULTS: A new
      relationship was found between Zn in prostate tissue and PSA in blood, which
      allows improved separation between prostate cancer and benign prostate
      hyperplasia, and might have a significant impact on the reliable diagnosis of
      prostate cancer. CONCLUSIONS: Zn concentration is not uniform even in the same
      anatomical region of the prostate, so that a number of measurements at various
      locations are required for a diagnostic procedure. The most interesting finding
      in this study is the relationship between Zn concentration and PSA. A combination
      of these parameters represents a significant improvement on the diagnostic value
      of each of them separately and provides a powerful tool for more accurate
      diagnosis. Although the method may be applied in vitro on biopsy samples, our
      study underlines the importance of developing a facility for in vivo Zn
      determination in the prostate.

PMID- 14634393
TI  - Genetic profiling of Gleason grade 4/5 prostate cancer: which is the best
      prostatic control tissue?
AB  - PURPOSE: We examined the variation in gene expression profiles of prostate cancer
      caused by zone specific genes. MATERIALS AND METHODS: Ten normal central zone, 10
      transition zone (benign prostatic hyperplasia) and 6 normal peripheral zone
      tissues from radical retropubic prostatectomies were compared to each other and
      to 12 peripheral zone Gleason grade 4/5 cancers. Test chips and HuGeneFL6800
      (Affymetrix, Inc., Santa Clara, California) chips were used to assay the
      transcribed genes. Data were obtained with the Microarray Suite Version 4.0.1
      (Affymetrix, Inc.) and analyzed statistically. RESULTS: Substantially different
      gene expression profiles were found depending upon which of the 3 zonal tissues
      were used as a control. All 3 profiles were compared for efficiency (ability to
      locate genes) and for robustness (the magnitude of difference between the control
      and the Gleason grade 4/5 tissue). Microscopically normal appearing peripheral
      zone tissue at the gene level shows many characteristics of Gleason grade 4/5
      cancer. CONCLUSIONS: Gene expression profiles of prostate cancer are affected by
      the zonal location of the control tissue and the cancer.

PMID- 14634394
TI  - Total and Gleason grade 4/5 cancer volumes are major contributors of human
      kallikrein 2, whereas free prostate specific antigen is largely contributed by
      benign gland volume in serum from patients with prostate cancer or benign
      prostatic biopsies.
AB  - PURPOSE: We measured concentrations of human glandular kallikrein 2 (hK2), total
      prostate specific antigen (tPSA), free PSA (fPSA) and percent fPSA to evaluate
      their relationship to total prostate gland volume, benign prostatic hyperplasia
      (BPH) volume, total prostate cancer (PCa) volume (CaVol) and the volume of
      Gleason grades 4/5 cancer (CaVolGl4) in the serum of 256 patients with PCa
      undergoing radical retropubic prostatectomy and 185 with negative systematic
      sextant biopsies. MATERIALS AND METHODS: Free and total PSA was measured using
      the Delfia Prostatus (Perkin-Elmer, Turku, Finland) total/free PSA assay and hK2
      was measured using a research immunofluorometric assay. Transrectal ultrasound
      was used to determine total prostate and BPH volume. Total CaVol and CaVolGl4/5
      were calculated using a volumetric program in specimens from 158 men with pT2a/b
      and 98 with pT3a or greater PCa. The Pearson correlation was performed after
      logarithmic conversion of PSA and hK2 levels. Benign gland, and pT2a/b and pT3a
      or greater PCa cases were subdivided into small vs large prostate gland volumes
      (42 cc or less vs greater than 42 cc). RESULTS: Total prostate and BPH volumes
      correlated closely with free PSA (r = 0.64 to 0.65, p <0.0001) in 143 patients
      with negative biopsy and a prostate of greater than 42 cc. Correlations of hK2
      and tPSA with total prostate and BPH volumes were weaker (r = 0.35 to 0.36 and
      0.45 to 0.46, respectively). In pT2a/b and pT3a or greater PCa cases hK2 most
      closely correlated with CaVol (range 0.31 to 0.62, p = 0.0072 and <0.0001) and
      with CaVolGl4/5 (range 0.26 to 0.56, p = 0.021 and <0.0001, respectively). The
      tPSA level correlated significantly with CaVol and CaVolGl4/5 except in glands 42
      cc or greater harboring pT2a/b PCa (p = 0.08). Free PSA correlated significantly
      with CaVolGl4/5 only in pT3a or greater PCa (p <0.05), and with CaVol in pT3a or
      greater PCa and in small prostates harboring pT2a/b PCa. CONCLUSIONS: Large
      benign prostate gland volume affects fPSA more than tPSA in serum. In PCa hK2
      more closely correlates with total cancer volume and high grade PCa volume
      compared with tPSA or fPSA.

PMID- 14634395
TI  - Can prostate specific antigen derivatives and pathological parameters predict
      significant change in expectant management criteria for prostate cancer?
AB  - PURPOSE: A prior report established that pretreatment criteria based on clinical
      and biopsy pathology parameters can predict men who harbor small volume prostate
      cancer who might be followed expectantly. However, some of these men will exhibit
      disease progression with time and will need definitive therapy. To detect those
      in whom disease may progress, repeat prostate biopsies are performed at yearly
      intervals. Therefore, we determined whether biomarkers could be used to determine
      those in whom disease is likely to progress and thus those who require definitive
      therapy. MATERIALS AND METHODS: Initial and repeat biopsy information along with
      transrectal ultrasound measurements of gland volume, total prostate specific
      antigen (PSA), %free PSA (%fPSA) and total PSA velocity were evaluated in 78 men,
      45 from the prior study, in whom disease was being managed expectantly.
      Univariate and multivariate logistic regression analyses determined variables
      that predicted a favorable tumor burden based on biopsy pathology status at each
      subsequent repeat biopsy. A Cox proportional hazards model was produced using 67
      of 78 evaluable cases having adequate temporal data to predict hazard ratios for
      conversion from favorable to unfavorable tumor burden status. RESULTS: At time
      zero for 78 patients %fPSA, total PSA, and gland volume univariately and
      multivariately differentiated unfavorable and favorable tumor burden groups (p
      <0.05). The receiver operator characteristic area under the curve (ROC-AUC) was
      83%. At the first followup biopsy 17 of 67 (25.4%) men converted to unfavorable
      tumor burden status. The %fPSA, PSA velocity and gland volume univariately
      distinguished these 2 groups (p <0.05) with 82% ROC-AUC. At second repeat biopsy
      6 of 36 (16.7%) men converted to unfavorable tumor burden status and the ROC-AUC
      was 76%. Of the 14 men who had a third repeat biopsy all demonstrated favorable
      tumor burden status. A Cox proportional hazards model stratified the 67 of 78 men
      into high (48) and low risk (19) groups based on %fPSA at a 20% cutoff (p <0.01).
      Classification and regression tree analysis using logistic regression
      multivariately selected variables predicted favorable tumor burden status with an
      accuracy that ranged from 75% to 84% during our study. CONCLUSIONS: PSA velocity,
      %fPSA and gland volume information improves the prediction of men undergoing
      expectant management who are more likely to have small volume disease based on a
      12-core biopsy interpretation within the time of our observations. %fPSA proved
      to be a valuable marker to stratify the 2 risk groups. Therefore, based on these
      factors it may be possible to consider deferment of repeat prostate biopsy until
      adverse results are detected. This rational approach to the management of
      prostate cancer in older men with small volume cancer seems to be a reasonable
      strategy.

PMID- 14634396
TI  - Predictors of treatment after initial surveillance in men with prostate cancer:
      results from CaPSURE.
AB  - PURPOSE: Expectant management of prostate cancer or watchful waiting (WW) is a
      reasonable option for some men with clinically localized prostate cancer. We
      identified predictors of eventual prostate cancer treatment in a cohort of men
      initially choosing WW. MATERIALS AND METHODS: We identified 457 men in the Cancer
      of the Prostate Strategic Urologic Research Endeavor data base selecting WW as
      initial management without subsequent treatment for at least 6 months. A subset
      of these men eventually received active treatment for prostate cancer. These
      groups were compared with respect to baseline clinical, sociodemographic
      characteristics and followup prostate specific antigen (PSA) characteristics
      using Kaplan-Meier life tables and Cox proportional hazards models to determine
      predictors of active treatment after WW. RESULTS: Of the 457 men initially on WW
      188 (41%) went on to active treatment at a median of 1.7 years after diagnosis.
      Baseline characteristics associated with progression to active treatment included
      younger age, higher level of formal education, higher PSA and higher Gleason
      grade. Actuarial freedom from treatment (that is continued WW) was 74% at 2, 63%
      at 3 and 49% at 5 years with androgen deprivation the most common form of therapy
      (72%). Men progressing to treatment had higher baseline and followup PSA as well
      as a significantly greater PSA change that those remaining on WW (7.2 vs -0.4
      ng/ml). Other measures of PSA dynamics also predicted eventual active treatment.
      These observations persisted in multivariate models. CONCLUSIONS: WW is an
      appropriate and common form of treatment in many men with prostate cancer and
      about half remain on WW at 5 years. Our analysis of national practice patterns
      identified demographic, clinical and PSA characteristics associated with men who
      continue with this modality. Conversely these factors may help determine which
      men (for example higher risk/PSA) ultimately receive active treatment despite
      initial treatment preference and allow investigation of the effects of these
      interventions on cancer outcomes and quality of life.

PMID- 14634397
TI  - Patient followup after radical prostatectomy by Internet medical file.
AB  - PURPOSE: The development of the Internet and the need for regular followup of
      patients often living a long way from the hospital led us to develop a followup
      dossier for those with localized prostate cancer treated with laparoscopic
      radical prostatectomy. MATERIALS AND METHODS: This feasibility study was based on
      140 patients who agreed to test this system. The website was opened on a server
      specifically devoted to this project with all required computer security. The
      website is composed of pages comprising the hospital discharge summary, and
      operative and histology reports. A quality of life questionnaire based on the
      assessment of urinary continence and sex life, and a prostate specific antigen
      (PSA) assay form are also included. RESULTS: The patient is able to enter his PSA
      data and complete the questionnaire at home. Results are then sent to the
      treating physician. A contact page allows the patient and physician to exchange
      information by text. Of these 100 patients 92 connected regularly to the site
      with a mean connection rate of 8 per patient (range 1 to 22). Of the patients 98%
      were satisfied with the various sections of the site, 95% were satisfied with the
      medical file, 11% noticed connection problems and 14% reported technical problems
      essentially attributable to incorrect PSA data entry or incorrect functioning of
      videos due to the absence of appropriate software. CONCLUSIONS: This type of
      Internet medical service for patients who have undergone surgery requiring
      regular followup appears to be a useful approach for the future by allowing the
      maintenance of close contact between the patient and physicians, while avoiding
      problems related to hospital visits regardless of the patient place of residence.
      It also provides general practitioners with access to the patient file with
      patient permission.

PMID- 14634398
TI  - Is Hispanic race an independent risk factor for pathological stage in patients
      undergoing radical prostatectomy?
AB  - PURPOSE: Hispanic-Americans are the most rapidly growing population in the United
      States. Although many studies have assessed differences in pathological stage at
      radical prostatectomy between white and black American men, to our knowledge none
      has assessed it in Hispanic men. We compared pathological stage at radical
      prostatectomy in contemporaneous groups of Hispanic and white American men.
      MATERIALS AND METHODS: A total of 141 consecutive Hispanic and 314 consecutive
      white American men underwent radical retropubic prostatectomy for clinically
      localized prostate cancer from 1995 to 2002 at a single institution, as performed
      by one of us (ETG or MCB). Preoperative prostate specific antigen (PSA), age at
      diagnosis, race, clinical stage, biopsy and specimen Gleason score, pathological
      stage, specimen volume and calculated specimen PSA density were collected for
      each patient. Data were compared using standard statistical methods. RESULTS:
      Biopsy Gleason score, biopsy Gleason score distribution, specimen Gleason score,
      specimen Gleason distribution, pathological stage, calculated specimen PSA
      density, Gleason score change from biopsy to specimen and specimen prostate
      volume did not differ statistically between Hispanic and white men. Mean age and
      median preoperative PSA were statistically significantly higher in Hispanic vs
      white men (62.1 vs 59.5 years and 6.6 vs 5.4 ng/ml, respectively). In addition,
      no differences in the incidence of positive surgical margins, nonorgan confined
      disease, seminal vesicle invasion or positive lymph nodes were found between
      Hispanic and white men undergoing radical prostatectomy. CONCLUSIONS: This study
      shows that in contemporaneously treated groups of Hispanic and white men at the
      same institution pathological stage was similar between the groups. To our
      knowledge this is the largest comparison of surgically treated prostate cancer
      between these 2 groups. Further followup in terms of PSA outcome in these groups
      is planned.

PMID- 14634399
TI  - Variations among individual surgeons in the rate of positive surgical margins in
      radical prostatectomy specimens.
AB  - PURPOSE: Cancer at the resection margin (a positive surgical margin) after
      radical prostatectomy is associated with an increased risk of recurrence even
      after adjusting for other known risk factors, including pretreatment serum
      prostate specific antigen (PSA), clinical stage, grade and pathological stage
      (level of extracapsular extension, seminal vesicle invasion and pelvic lymph node
      status). Of these prognostic factors only surgical margin status can be
      influenced by surgical technique. We examined variations in the rate of positive
      surgical margins among surgeons after controlling for the severity of disease and
      volume of cases per surgeon. MATERIALS AND METHODS: A total of 4,629 men were
      treated with radical prostatectomy by 1 of 44 surgeons at 2 large urban centers
      between 1983 and 2002 for clinical stage T1-T3NxM0 prostate cancer. Patients were
      excluded if they had previously received androgen deprivation therapy or
      radiation therapy to the pelvis. Positive surgical margins were defined as cancer
      at the inked resection margin. Other risk factors analyzed were serum PSA, grade
      (Gleason sum), extracapsular extension level (none, invasion into the capsule,
      present [not otherwise specified], focal extracapsular extension or established
      extracapsular extension), seminal vesicle invasion, pelvic lymph node metastases,
      surgery date, surgeon and volume of cases per surgeon. RESULTS: For the 26
      surgeons who each treated more than 10 patients in the study the rate of positive
      surgical margins was 10% to 48%. On multivariable analysis higher serum PSA,
      extracapsular extension level, higher radical prostatectomy Gleason sum, surgery
      date, surgical volume and surgeon were associated with surgical margin status
      after controlling for all other clinical and pathological variables. CONCLUSIONS:
      While the clinical and pathological features of cancer are associated with the
      risk of a positive margin in radical prostatectomy specimens, the technique used
      by individual surgeons is also a factor. Lower rates of positive surgical margins
      for high volume surgeons suggest that experience and careful attention to
      surgical details, adjusted for the characteristics of the cancer being treated,
      can decrease positive surgical margin rates and improve cancer control with
      radical prostatectomy.

PMID- 14634400
TI  - No apparent benefit at 5 years from a course of neoadjuvant/concurrent androgen
      deprivation for patients with prostate cancer treated with a high total radiation
      dose.
AB  - PURPOSE: We examined the survival impact of a course of 6 months or less of
      adjuvant/concurrent androgen deprivation in patients with unfavorable prostate
      cancer treated to high radiation doses with external beam (EBRT) and a high dose
      rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Between 1986 and 2000, 507
      patients were treated with pelvic EBRT (46 Gy) with HDR prostate brachytherapy as
      a boost. The biological equivalent EBRT dose was between 90 and 130 Gy. At Kiel
      University and at William Beaumont Hospital 198 and 309 patients were treated.
      Patient eligibility was pretreatment prostate specific antigen 10 ng/ml or
      greater, Gleason score 7 or greater, or clinical stage T2b or greater. The
      brachytherapy dose was escalated from 5.5 x 3 to 15 x 2 Gy. Patients were divided
      between 177 receiving and 330 not receiving androgen suppression therapy (AST).
      AST was given for a mean of 6 months. The American Society for Therapeutic
      Radiology and Oncology biochemical failure definition was used. RESULTS: Mean
      patient age was 68 years. Mean followup was 4.8 years (range 0.7 to 15.3), that
      is 4.5 years for AST and 4.9 for radiation alone. Five-year actuarial rates for
      biochemical control were 74% and 76%, for overall survival they were 81% and 87%,
      and for disease-free survival they were 67% and 66%, while cause specific
      survival with and without AST was 90% and 98%, and the 5-year metastatic rates
      were 10.7% and 6.9%, respectively. On multivariate analysis AST did not improve
      biochemical control. CONCLUSIONS: Pelvic EBRT interdigitated with a transrectal
      ultrasound guided HDR boost is an excellent method of delivering a high radiation
      dose to the prostate without rendering the patient radioactive. This trial showed
      high overall, cause specific and no biochemical evidence of disease survival. For
      this unfavorable group of patients the addition of a course of 6 months or less
      of neoadjuvant/concurrent AST to a high radiation dose did not appear to confer a
      5-year therapeutic advantage. However, it added side effects and the significant
      cost of hormones.

PMID- 14634401
TI  - Serum osteoprotegerin and receptor activator of nuclear factor-kappa B ligand as
      indicators of disturbed osteoclastogenesis in patients with prostate cancer.
AB  - PURPOSE: We evaluated the behavior and diagnostic usefulness of the
      osteoclastogenesis proteins osteoprotegerin and receptor activator of nuclear
      factor-kappaB ligand (RANKL) in the serum of patients with prostate cancer (PCa).
      MATERIALS AND METHODS: Serum osteoprotegerin and RANKL were retrospectively
      measured in 117 patients with prostate cancer, including 39 with stage pN0M0, 34
      with stage pN1M0 and 44 with bone metastases, in 35 presumably healthy men and in
      35 patients with benign prostatic hyperplasia (BPH). The association of these
      components with clinical data (tumor stage and grade) and receiver operating
      characteristics curves compared with the bone formation marker alkaline
      phosphatase and bone resorption marker crosslaps (cross-linked C-terminal
      telopeptides of type I collagen) were calculated. RESULTS: Osteoprotegerin was
      increased in patients with bone metastases, while those with localized cancer or
      lymph node metastases had values similar to those in presumably healthy controls
      and patients with BPH. RANKL did not differ among the control, BPH and PCa
      subgroups. Thus, the ratio of osteoprotegerin-to-RANKL showed behavior similar to
      that of osteoprotegerin. Osteoprotegerin and RANKL did not show any significant
      correlation with tumor stage, histological tumor grade, total prostate specific
      antigen, alkaline phosphatase activity or crosslaps. ROC analysis data proved
      that osteoprotegerin had a better diagnostic accuracy than alkaline phosphatase
      or crosslaps for detecting bone metastases in PCa cases. CONCLUSIONS: Serum
      osteoprotegerin but not RANKL indicates disturbed osteoclastogenesis in patients
      with PCa and bone metastatic spread. It could be used as a marker for bone
      metastases.

PMID- 14634402
TI  - The predictors of pelvic lymph node metastasis at radical retropubic
      prostatectomy.
AB  - PURPOSE: We studied preoperative variables in a contemporary series of patients
      who underwent radical retropubic prostatectomy (RRP) to determine which variables
      were associated with lymph node metastasis. MATERIALS AND METHODS: Between
      January 1995 and November 1999, 1,091 men underwent RRP, 695 of whom underwent
      bilateral pelvic lymph node dissection without any prior therapy. We evaluated
      biopsy Gleason score, maximum tumor length and maximum percentage of tumor in the
      positive core(s), location and number of positive cores, and total prostate
      specific antigen before surgery in 295 of these patients. We also developed a
      classification and regression tree analysis algorithm to segregate the risk of
      positive lymph node metastasis. Stepwise logistic regression analyses were used
      to determine independent predictors of lymph node metastasis. RESULTS: Of the 695
      patients 19 (2.7%) had lymph node metastasis. Clinical stage, Gleason score,
      positive basal core, greatest percentage of tumor on positive cores and maximum
      tumor length in positive core were significant predictors of lymph node
      metastasis in the Mann-Whitney U test and chi-square test. Classification and
      regression trees analysis revealed that 4 or more positive cores with any Gleason
      grade 4 or 5, serum prostate specific antigen 15.0 ng/ml or greater, or the
      presence of dominant Gleason 4 or 5 were independent predictors of lymph node
      metastasis. Our algorithm had a significantly higher diagnostic performance than
      the Hamburg algorithm (p = 0.002). CONCLUSIONS: Our algorithm may be a valid tool
      for the prediction of lymph node metastasis and may help to select men who do not
      need to undergo bilateral pelvic lymph node dissection with RRP.

PMID- 14634403
TI  - Management of trauma to the male external genitalia: the usefulness of American
      Association for the Surgery of Trauma organ injury scales.
AB  - PURPOSE: Injury to the male external genitalia is rare and, therefore, there are
      little data in the literature regarding the options for nonoperative management
      and outcome. To assist in defining the indications for nonoperative management
      the usefulness of the American Association for the Surgery of Trauma (AAST) organ
      injury scales for these injuries was examined. MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of 116 male patients with trauma to
      the external genitalia in a 10-year period and classified injuries according to
      the organ injury severity scales (scrotum, testis, penis and urethra) of the
      AAST. Based on AAST grading management and outcome was reviewed. RESULTS: Mean
      patient age was 28 years and 79% of the injuries were due to gunshot wounds. A
      total of 87 patients (75%) underwent surgery, while 27 penile injuries and 8
      scrotal/testicular injuries were managed nonoperatively. There were 54 scrotal
      explorations, 33 testicular injuries and 20 orchiectomies (bilateral in 1) for a
      testicular salvage rate of 39%. Documented followup by the trauma or
      genitourinary service was achieved in 47 of 110 survivors. No patient reported
      impotence or difficulty with fertility. CONCLUSIONS: The AAST grading for male
      external genital trauma readily characterizes patients with high grade injuries
      that require operative management as well as select patients in whom injury can
      be safely managed nonoperatively.

PMID- 14634404
TI  - Rectal sensation test helps avoid pain of apical prostate biopsy.
AB  - PURPOSE: Apical cores obtained during transrectal prostate biopsy are associated
      with greater pain than cores obtained from the remainder of the gland. We present
      a method to minimize this pain. MATERIALS AND METHODS: During 30 consecutive
      apical biopsies the needle was purposefully placed above all rectal pain fibers,
      which are anatomically present only below the dentate line. All patients received
      a periprostatic nerve block prior to biopsy. The patient was asked if he felt the
      sharp sensation of the needle as it was placed lightly against the rectal mucosa
      when the needle was aimed at apex (the rectal sensation test). If so, the needle
      was advanced cranially 2 to 3 mm or until he could no longer detect its light
      touch. The probe handle was then rotated dorsally, pulling the rectal mucosa
      downward until the needle was again aimed at the apex. Patients were asked to
      report a visual analog pain score for each biopsy. These results were compared to
      those obtained when doing 30 consecutive apical biopsies without the rectal
      sensation test. RESULTS: The average visual analog pain score for apical biopsy
      was 1.25 (range 0 to 2.2) for patients in whom the rectal sensation test was used
      to bypass rectal pain sensory fibers. The average score in control patients in
      whom the rectal sensation test was not used was higher at 2.28 (range 0.3-6.2).
      These results were statistically significant (p > 0.0005). CONCLUSIONS: Increased
      sensitivity to apical prostate biopsy is due to rectal pain fibers located below
      the dentate line. These fibers and the associated pain may be safely avoided by
      passing through the rectal wall above the dentate line. The rectal sensation test
      easily identifies the sensate area below the dentate line. Painless apical biopsy
      can then be achieved by rotating the ultrasound probe to aim the biopsy needle in
      the desired path.

PMID- 14634405
TI  - The optimum doses of and injection locations for periprostatic nerve blockade for
      transrectal ultrasound guided biopsy of the prostate: a prospective, randomized,
      placebo controlled study.
AB  - PURPOSE: We evaluated the efficiency of various amounts of local anesthesia and
      various numbers of injection sites to determine the most effective pain control
      with the least number of injections and the amount of injected medium in patients
      who underwent transrectal ultrasound guided prostate biopsy. MATERIALS AND
      METHODS: Transrectal ultrasound guided 8 core biopsy of the prostate was
      performed in 175 consecutive men. Patients were randomized into 7 groups with 25
      per group. Group 1 received 5 cc saline and groups 2 to 7 received 2.5, 5 or 10
      cc 1% lidocaine injected as local anesthesia at basal or basal plus apical
      locations. The patients were then evaluated for pain and other complications to
      determine whether there was a difference regarding groups. RESULTS: Mean pain
      scores were significantly lower than in saline group for all anesthesia injected
      groups except group 2 with a 2.5 cc bilateral basal injection. The most effective
      pain control was achieved by 10 cc anesthetic injections. Basal plus apical
      injections were not superior than only basal injections for pain control. There
      was no significant difference in the hematuria, hematospermia, rectal bleeding or
      infection rate among the groups. Increasing the number of injections and amount
      of lidocaine had no effect on complication rates. CONCLUSION: Our placebo
      controlled, prospective, randomized study indicated that 10 cc local anesthetic
      injections supply significantly better pain control than lower doses for
      periprostatic nerve blockade during prostate biopsy. Although bilateral basal
      plus apical 10 cc lidocaine injections resulted in the lowest mean pain score,
      there was no statistically significant difference from 10 cc bilateral basal
      injections.

PMID- 14634406
TI  - Neurophysiological evidence may predict the outcome of sacral neuromodulation.
AB  - PURPOSE: Chronic stimulation of the sacral nerves has now become one of the most
      accepted stimulation therapies for functional lower urinary tract symptoms
      refractory to conservative treatment. Despite the existence of a large amount of
      literature on sacral neuromodulation (SNM) showing a fairly high percent of
      significant improvement in clinical outcome there are few experimental studies of
      SNM stimulus parameters and/or neurophysiological monitoring. We evaluated the
      specific action of SNM on the primary sensory cortical area. Somatosensory evoked
      potentials (SEPs) of the pudendal and posterior tibial nerves were evaluated in
      patients implanted with a monolateral permanent quadripolar electrode. MATERIALS
      AND METHODS: A total of 24 patients underwent stage 1 monolateral sacral nerve
      implantation. Three SEP patterns were evaluated; namely before implantation, 1
      month after stage 1 with stimulation set at 21 Hz and again with a pulse rate of
      40 Hz. RESULTS: In all patients SNM produced a significant decrease in pudendal
      SEP latency of the first positive deflection between baseline SNM stimulation at
      different pulse rates at the ipsilateral and contralateral implant sites. This
      finding was evidence of the effect of S3 SNM on the cortical sensory area and the
      specificity of pudendal SEPs in measuring how SNM modulates the afferent pathway
      from the spinal nerve to the cortical sensory area. CONCLUSIONS: Our study
      confirms previous observations that SNM acts by the afferent pathway at the
      cortical site level and it sheds light on so-called idiopathic lower urinary
      tract symptoms. A modification of SEPs induced by SNM seems to be a prognostic
      factor of clinical outcomes. The action of SNM on the afferent pathway from the
      sacral area to the somatosensory cortex is specific and neurophysiological
      evaluation via pudendal SEPs provides evidence to this effect.

PMID- 14634407
TI  - New periurethral bulking agent for stress urinary incontinence: modified
      technique and early results.
AB  - PURPOSE: Durasphere (Carbon Medical Technologies, St. Paul, Minnesota) is a newly
      approved injectable agent for stress urinary incontinence. Proven and potential
      advantages include nonimmunogenicity, tissue nonreactivity, efficacy at low
      injectable volume and durability. A concern regarding use is difficulty involved
      with application. A modified technique for easier implantation of this agent is
      described and early results are reported. MATERIALS AND METHODS: The surgical
      technique follows the standard technique for transurethral implantation of
      bulking agents. Steps modified to allow easier implantation of Durasphere beads
      include a single needle stick at the 4 o'clock position, hydrodissection with 1.5
      ml 1% lidocaine into the submucosa, gradual withdrawal/advancement or rotation of
      the needle tip after resistance is noted and holding the needle in position for
      an additional 10 seconds after proper coaptation is achieved to prevent the beads
      from leaking out of the needle puncture site. Patient charts were retrospectively
      reviewed. Patient perception of treatment outcomes, a 24-hour pad test and a
      voiding diary were obtained and analyzed. The strict criteria of the Groutz
      Blaivas score were applied as an additional measure of outcome. RESULTS: Of 70
      patients 46 (65.7%) for whom full contact information was available responded.
      Patient age was 46 to 83 years (mean 69.4). A history of a failed prior anti
      incontinence procedure was recorded in 15 patients (32.6%) and coexisting
      symptoms of urge incontinence or urodynamically proven detrusor instability was
      evident in 29 (63%) and 5 (10.8%), respectively. Bulking agent was delivered at 1
      to 3 sessions (mean 1.52) 1 to 3 months apart with 2 to 6 ml (3.2 ml) injected
      per session. Excellent or good coaptation was achieved in 92% of injections. At a
      followup of up to 18 months (mean 9.4) 6 (13%), 24 (52.2%) and 16 (34.7%)
      patients considered themselves cured or improved, or treatment to have failed,
      respectively. Of the 36 patients who completed a 24-hour pad test 18 (50%), 2
      (5.5%) and 16 (44.4%) had a urine loss of 8 or less, 9 to 20 and greater than 20
      gm, respectively. Results of the voiding diary and the Groutz-Blaivas score are
      provided. CONCLUSIONS: The modified technique of Durasphere injection allows easy
      implantation with good coaptation in the majority of patients. Early results are
      encouraging. Further research may reveal whether the improved delivery techniques
      translate into improved outcomes with more durable results compared with other
      approved bulking agents.

PMID- 14634408
TI  - Combined vaginoscopy-cystoscopy: a novel simultaneous approach improving
      vesicovaginal fistula evaluation.
AB  - PURPOSE: Using a device that permits simultaneous viewing on the same display
      (picture in picture) of 2 images we performed combined vaginoscopy-cystoscopy
      (CVC) during evaluation for vesicovaginal fistula as a means of better
      visualization, allowing more precise identification and better preoperative
      planning. MATERIALS AND METHODS: A regular cystoscope and a 10 mm 0-degree
      laparoscope were used. Each was attached to a different microcamera and light
      source. The cameras were hooked to the back of a Twinvideo (Karl Storz Endoscopy,
      Tuttlingen, Germany), allowing a wide variety of views combining the 2 images.
      Cystoscopy was performed as usual and the laparoscope was used for vaginoscopy
      with a transparent vaginal speculum to maintain the vagina open, while allowing
      visualization of the vaginal wall. The 2 images were combined in picture in
      picture, providing confidence during the fistula identification process. Urinary
      leakage was viewed simultaneously with guide wire passage through the cystoscope
      and vaginal wall, showing the exactly fistula position. RESULTS: The CVC
      procedure using 2 images in picture in picture allows precise identification
      during evaluation for vesicovaginal fistula. CONCLUSIONS: CVC has become a
      routine procedure in suspicious cases or in those of a confirmed diagnosis of
      vesicovaginal fistula at our institution. It increases the likelihood of fistula
      diagnosis and identification, allowing better surgical planning.

PMID- 14634409
TI  - Safety and efficacy of sildenafil citrate for the treatment of female sexual
      arousal disorder: a double-blind, placebo controlled study.
AB  - PURPOSE: We evaluated the efficacy and safety of sildenafil citrate in
      spontaneously or surgically postmenopausal women with female sexual arousal
      disorder (FSAD). MATERIALS AND METHODS: Sildenafil (a 50 mg dose adjustable to
      100 or 25 mg) was evaluated in a 12-week, double-blind, placebo controlled study
      in 202 postmenopausal women with FSAD who had protocol specified estradiol and
      free testosterone concentrations, and/or were receiving estrogen and/or androgen
      replacement therapy. Patients were excluded if emotional, relationship or
      historical abuse issues contributed significantly to sexual dysfunction. Primary
      end points were questions 2 (increased genital sensation during intercourse or
      stimulation) and 4 (increased satisfaction with intercourse and/or foreplay) from
      the Female Intervention Efficacy Index (FIEI). Secondary end points were the
      remaining questions from this index, the Sexual Function Questionnaire and sexual
      activity event log questions. RESULTS: Significant improvements in FIEI questions
      2 (p = 0.017) and 4 (p = 0.015) were noted with sildenafil compared with placebo.
      For women with FSAD without concomitant hypoactive sexual desire disorder (HSDD)
      sildenafil was associated with significantly greater improvement in 5 of 6 FIEI
      items compared with placebo (p <0.02). No significant improvements were shown for
      women with concomitant HSDD. Most adverse events were mild to moderate with
      headache, flushing, rhinitis, nausea and visual symptoms reported most
      frequently. CONCLUSIONS: Sildenafil was effective and well tolerated in
      postmenopausal women with FSAD without concomitant HSDD or contributory
      emotional, relationship or historical abuse issues. All patients had protocol
      specified estradiol and free testosterone concentrations or were receiving
      estrogen and/or androgen replacement therapy.

PMID- 14634410
TI  - Intravesical prostatic protrusion predicts the outcome of a trial without
      catheter following acute urine retention.
AB  - PURPOSE: We prospectively evaluated a simple, noninvasive method to predict the
      outcome of a voiding trial following acute urine retention (ARU) based on
      intravesical prostatic protrusion (IPP) using transabdominal ultrasound.
      MATERIALS AND METHODS: Males older than 50 years presenting with an initial
      episode of ARU were included in the study. Patients with prostatic cancer,
      urinary tract infection, bilateral hydronephrosis or neurological disease were
      excluded. The duration of catheterization, residual urine volume, serum prostate
      specific antigen and prostate volume were recorded. The patient bladder was
      filled with 200 ml normal saline via a catheter in situ. IPP was measured in the
      mid sagittal section using transabdominal ultrasound. The degree of protrusion
      was classified as grades 1--5 mm or less, 2--greater than 5 to 10 mm and 3-
      greater than 10 mm. Uroflowmetry and post-void residual urine were recorded after
      catheter removal. The voiding trial was judged to be unsuccessful if the patient
      failed to reestablish satisfactory micturition, with post-void residual urine
      greater than 100 ml and maximum urine flow less than 10 ml per second. RESULTS: A
      total of 100 patients were included in the study. The failure rate of the voiding
      trial based on grades 1 to 3 IPP were 36% (13 of 36 cases), 58% (11 of 19) and
      67% (30 of 45). This rate was significant (chi-square test for trend 0.007).
      CONCLUSIONS: IPP is a useful predictor for evaluating the success of a voiding
      trial following ARU. Patients with a grade 1 prostate may benefit from a trial
      without a catheter. However, patients with a grade 3 prostate are less likely to
      do so and would require a more definitive surgical procedure.

PMID- 14634411
TI  - Prevalence and severity of erectile dysfunction in 50 to 75-year-old Finnish men.
AB  - PURPOSE: We estimated the prevalence and severity of erectile dysfunction (ED) in
      a population based sample of 50 to 75-year-old Finnish men. MATERIALS AND
      METHODS: The target population consisted of all noninstitutionalized men 50, 60
      or 70 years old residing in the study area in 1994. Questionnaires were mailed to
      3,143 men in 1994 and to 2,864 men 5 years later. ED was assessed by 2 questions
      on subject ability to achieve and maintain erection sufficient for intercourse.
      Subjects were classified for analysis into none, minimal, moderate and complete
      ED groups. RESULTS: The overall prevalence of ED was 76.5%. The prevalence of ED
      increased from 67% for men 50 years old to 89% for those 75 years old. The
      prevalence of moderate and complete ED was 29%, increasing rapidly with age from
      12% for age 50 years to 58% at age 75 years. Moderate ED increased by 8%, whereas
      complete ED increased by 18% for each 1-year age increment. CONCLUSIONS: ED is a
      highly prevalent disorder in 50 to 75-year-old men. It increases with age and is
      markedly higher after age 60 years. The prevalence of moderate ED increases
      linearly and slowly, while that of complete ED increases exponentially and
      rapidly with advancing age.

PMID- 14634412
TI  - Bioavailable testosterone with age and erectile dysfunction.
AB  - PURPOSE: Symptoms of partial androgen deficiency of the aging male (PADAM), such
      as sexual dysfunction and depression, are receiving increased attention.
      Currently bioavailable testosterone (BT) is considered the most reliable marker
      for establishing the presence of hypogonadism. We clarified the relationship
      between BT and other hormones with respect to patient age and PADAM symptoms.
      MATERIALS AND METHODS: A total of 130 patients who visited our special clinics
      for sexual function were included in this study. Endocrinological profiles were
      evaluated as appropriate, and sexual dysfunction and depression as symptoms of
      PADAM were assessed by a self-reported questionnaire. The relationship between
      age and several measures of testosterone, between BT and other hormonal measures,
      and between BT and PADAM symptoms were analyzed. RESULTS: Although serum total
      testosterone did not decrease with age, sex hormone binding globulin increased
      significantly. BT and free testosterone decreased significantly, and total and
      free testosterone correlated significantly with BT. The International Index of
      Erectile Function-5 score for erectile function increased significantly with
      increases in BT. However, the relationship between the depression score and BT
      was not significant. CONCLUSIONS: We consider that BT is a useful marker for
      diagnosing and treating patients with PADAM because BT correlates significantly
      with age and International Index of Erectile Function-5 scores. We emphasize that
      measuring serum testosterone is necessary in aging males.

PMID- 14634413
TI  - Testosterone replacement therapy in hypogonadal men at high risk for prostate
      cancer: results of 1 year of treatment in men with prostatic intraepithelial
      neoplasia.
AB  - PURPOSE: One of the greatest concerns among clinicians regarding testosterone
      replacement therapy (TRT) is the fear of causing or promoting prostate cancer. We
      evaluated prostatic changes in hypogonadal men with and without high grade
      prostatic intraepithelial neoplasia (PIN), which is considered a prostatic
      precancerous lesion, after 1 year of TRT. MATERIALS AND METHODS: A total of 75
      hypogonadal who completed 12 months of TRT were studied. All underwent prostate
      biopsy prior to initiating treatment. Of the men 55 had benign prostate biopsies
      (PIN-) and 20 had PIN without frank cancer (PIN+). All men with PIN underwent
      repeat biopsy to exclude cancer prior to the initiation of testosterone
      treatment. Prostate specific antigen (PSA), and total and free testosterone were
      determined prior to treatment and at 1 year. Repeat biopsy was performed for a
      change noted on digital rectal examination or for a PSA increase of 1 ng/l or
      greater. RESULTS: PSA was similar at baseline in men with and without PIN (1.49
      +/- 1.1 and 1.53 +/- 1.6 ng/dl, p >0.05) and after 12 months of TRT (1.82 +/- 1.1
      and 1.78 +/- 1.6 ng/dl, respectively, p >0.05). A slight, similar increase in
      mean PSA was noted in the PIN- and PIN+ groups (0.25 +/- 0.6 and 0.33 +/- 0.6
      ng/dl, p >0.05). One man in the PIN+ group had cancer after biopsy was performed
      due to abnormal digital rectal examination. Four additional men in the PIN- group
      and 2 in the PIN+ group underwent re-biopsy for elevated PSA and none had cancer.
      No differences were noted between the PIN- and PIN+ groups with regard to total
      and free testosterone at baseline and at 1 year (p = 0.267). CONCLUSIONS: After 1
      year of TRT men with PIN do not have a greater increase in PSA or a significantly
      increased risk of cancer than men without PIN. These results indicate that TRT is
      not contraindicated in men with a history of PIN.

PMID- 14634414
TI  - Clinical experience with apomorphine hydrochloride: the first 107 patients.
AB  - PURPOSE: We assessed the efficacy and safety of apomorphine hydrochloride in
      patients with erectile dysfunction. MATERIALS AND METHODS: A total of 107
      patients who had consultations because of erectile dysfunction between July and
      November 2001 were assessed. The sample was randomly selected. RESULTS: Response
      to apomorphine hydrochloride was assessed in 107 patients complaining of erectile
      dysfunction, randomly selected at the office. With the 2 mg initial dose the
      response amounted to 23.5%, with 3 mg it amounted to 28.5% and the global
      response to the drug amounted to 26.1%. Positive response was obtained in 18.5%
      of those in whom the dose was increased from 2 to 3 mg. Obtaining an erection
      with enough rigidity to enable coitus satisfactory for the patient was accepted
      as a positive response. According to the clinical presentation of the erectile
      dysfunction, the highest efficacy was found in those cases with early
      detumescence, and the lowest one in those cases with complete affection. The
      overall incidence of adverse effects was 8.4%, with nausea being the most
      frequently reported. CONCLUSIONS: Apomorphine hydrochloride is the first central
      action erection inducing drug. Its use is encouraged by high tolerability, low
      rate of adverse effects and virtually nonexistent interaction with other drugs
      usually administered to patients with erectile dysfunction.

PMID- 14634415
TI  - Salvage of sildenafil failures referred from primary care physicians.
AB  - PURPOSE: Sildenafil citrate is an effective first line agent for most causes of
      erectile dysfunction. Primary care providers (PCPs) write the majority of these
      prescriptions and most failures of sildenafil therapy are subsequently referred
      to urologists for alternative therapies. Often it is concluded that the drug is
      ineffective when in actuality the failure is do to inadequate patient education.
      We examined patients referred from PCPs who were nonresponders to sildenafil
      therapy and attempted to convert them to responders through reeducation.
      MATERIALS AND METHODS: In a 2-year period 253 sildenafil nonresponders were
      evaluated by the same urologist (GNS). Patient reeducation consisted of viewing a
      brief videotape, personal instruction and detailed instruction sheets for the
      patient and his partner. Outcome measures were obtained through patient self
      reporting of the Sexual Health Inventory for Men and a global assessment
      question. Responders were identified as those who answered positively latter or
      had a statistical improvement in the score of the former. RESULTS: Of the 253
      patients reeducated 17 were excluded due to contraindications. Of the remaining
      nonresponders 41.5% achieved salvage with reeducation. Incorrect administration
      accounted for 81% of the failures. Average time with the physician was 12 minutes
      and 94% of the patients continued to respond at 26 months. CONCLUSIONS:
      Approximately 40% of patients with sildenafil failures referred from PCPs can be
      converted to responders through reeducation. Incorrect drug administration was
      the most common reason for correctable failure. Reeducation can be done in an
      efficient manner. New package materials may improve sildenafil outcomes and
      compliance.

PMID- 14634416
TI  - Human cadaveric pericardial graft for the surgical correction of Peyronie's
      disease.
AB  - PURPOSE: In patients with stable penile deformity secondary to Peyronie's disease
      (PD) penile straightening can be achieved with plaque incision or partial
      excision and grafting. We present our experience with human cadaveric pericardium
      for tunica albuginea grafting for men undergoing penile reconstruction for
      Peyronie's disease. MATERIALS AND METHODS: We retrospectively reviewed our
      experience with 40 men with PD who underwent penile straightening with partial
      plaque excision and grafting using human cadaveric pericardium from January 1999
      to January 2003. RESULTS: All 40 men were evaluable for preoperative, operative
      and postoperative characteristics. Mean postoperative followup was 22.0 months.
      Mean preoperative penile curvature was 69.1 degrees. Subjectively 36 of the 40
      patients (90%) graded preoperative erection as sufficiently rigid for coitus and
      100% had sufficiently rigid erection for coitus following intracorporeal
      papaverine injection. Mean pericardial graft size was 4.9 x 4.8 cm.
      Postoperatively 39 of the 40 patients (98%) had successful penile straightening,
      38 (95%) achieved coitus, 28 (70%) achieved full, unaided erection and 12 (30%)
      had some degree of erectile dysfunction (ED) requiring pharmacological assistance
      for intercourse. There were no significant differences in ED risk factors, plaque
      location, graft size or complications in men who did and did not have ED
      postoperatively (p >0.05). There were no major complications or graft related
      adverse events. CONCLUSIONS: Human cadaveric pericardium is a safe, readily
      available and pliable tissue for tunica albuginea grafting following PD plaque
      incision or partial excision. Careful patient selection must be emphasized and
      particular attention must be given to deformity stability and preoperative
      erectile function to maximize surgical outcome.

PMID- 14634417
TI  - Soluble forms of Fas and Fas ligand concentrations in the seminal plasma of
      infertile men with varicocele.
AB  - PURPOSE: The Fas system in the testis has been identified as a key physiological
      regulator of apoptosis, an ongoing physiological process that limits the size of
      the germ cell population so it can be supported. Recently it was reported that
      the soluble form of Fas blocks Fas dependent apoptosis. In the present study we
      measured soluble Fas (sFas) concentrations in seminal plasma of oligozoospermic
      men with and without varicocele, and in normal men, looking for an association
      between seminal sFas and sFas ligand with spermatogenesis. MATERIALS AND METHODS:
      A total of 27 oligozoospermic men with varicocele, 59 oligozoospermic men without
      varicocele and 34 normal volunteers were included in this study. Patients were
      evaluated clinically according to the protocol of the World Health Organization.
      sFas and sFas ligand were measured using a commercially available double antibody
      enzyme linked immunoassay. Follicle-stimulating hormone, luteinizing hormone,
      testosterone and estradiol concentrations were determined by chemiluminescence
      assays. RESULTS: Seminal concentrations of sFas in oligozoospermic men with
      varicocele (3.6 +/- 2.4 ng/ml) were significantly lower than those in
      oligozoospermic men without varicocele (4.9 +/- 2.7 ng/ml, p = 0.0321) and normal
      men (5.1 +/- 2.4 ng/ml, p = 0.0201). The seminal sFas concentration significantly
      correlated with sperm concentration (r = 0.517, p = 0.0058). After
      varicocelectomy the increase in sperm concentration significantly correlated with
      an increase in sFas in seminal plasma (r = 0.555, p = 0.0026). The serum
      concentration of luteinizing hormone, follicle-stimulating hormone, testosterone
      or estradiol did not correlate significantly with the seminal sFas concentration.
      The sFas ligand concentration in seminal plasma was less than the limit of
      detection. CONCLUSIONS: The sFas concentration in seminal plasma shows a strong
      association with spermatogenesis. Subnormal levels of sFas may be responsible for
      increased apoptosis induced by the Fas system, resulting in impaired
      spermatogenesis in patients with varicocele.

PMID- 14634418
TI  - Intraoperative varicocele anatomy: a microscopic study of the inguinal versus
      subinguinal approach.
AB  - PURPOSE: The groin approach to varicocelectomy is performed by an inguinal
      (aponeurosis of external oblique opened) or subinguinal (external oblique
      aponeurosis intact) technique. We describe the number and relationship of
      internal and external spermatic arteries, veins and lymphatics within the
      subinguinal portion of the spermatic cord in infertile men undergoing microscopic
      varicocelectomy and compare these findings to the microanatomy observed with the
      inguinal approach. MATERIALS AND METHODS: A total of 48 consecutive patients
      underwent 84 microsurgical subinguinal varicocelectomies during which the
      detailed intraoperative microanatomy of the spermatic cord and gubernacula was
      recorded. These observations were compared with a previously reported group of 83
      consecutive patients that underwent 115 inguinal varicocelectomies. Subinguinal
      microscopic findings were also evaluated relative to clinical varicocele grade.
      RESULTS: The spermatic cord in the subinguinal dissection was characterized by a
      smaller number of large (greater than 5 mm) internal spermatic veins and a
      greater number of small (less than 2 mm) internal spermatic veins than the cord
      in the inguinal dissection (mean 0.4 vs 1.9 large veins and mean 7.9 vs 4.7 small
      veins, respectively). The subinguinal dissection was also characterized by a
      significantly greater percentage of external spermatic veins greater than 2 mm
      than that observed during inguinal dissection (93% vs 74%, respectively, p
      <0.05). Multiple spermatic arteries were identified in 75% of subinguinal
      dissections and in only 31% of inguinal dissections (p <0.03). Internal spermatic
      arteries were surrounded by a dense complex of adherent veins in 95% of cases
      using the subinguinal approach, whereas this finding was true in only 30% of
      cases with the inguinal approach (p <0.001). The clinical grade of a varicocele
      was significantly associated with the number of internal spermatic veins greater
      than 2 mm found intraoperatively (p <0.001) but not with the maximum internal
      spermatic vein diameter. CONCLUSIONS: Although the subinguinal approach to
      microsurgical varicocelectomy obviates the need to open the aponeurosis of the
      external oblique, it is associated with a greater number of internal spermatic
      veins and arteries compared with the inguinal approach. The primary branch point
      for the testicular artery occurs most commonly during its course through the
      inguinal canal. Internal spermatic arteries at the subinguinal level are more
      than 3 times as likely to be surrounded by a dense network of adherent veins than
      when they are identified at the inguinal level. Taken together, these data
      suggest that microscopic dissection is more difficult with a subinguinal
      incision.

PMID- 14634419
TI  - New scientific information related to varicoceles.

PMID- 14634420
TI  - Urinary continence and quality of life in the first year after radical perineal
      prostatectomy.
AB  - PURPOSE: We attempt to characterize the return of urinary continence and urinary
      domain related quality of life objectively after radical perineal prostatectomy
      (RPP). MATERIALS AND METHODS: A total of 92 RPP candidates were prospectively
      enrolled in a quality of life (QOL) survey using a validated assessment tool and
      evaluated before surgery, and then after surgery at 1 month and subsequent 3
      month intervals. The time to regain continence based on 3 different definitions
      and the time to recover baseline urinary domain related QOL was calculated.
      RESULTS: Median time to regain continence after RPP ranged from 3.0 to 3.3 months
      depending on the definition of continence. Median time for patients to regain
      continence depending on age (younger than 55, 55 to 64 and older than 64) and
      medical comorbidities (none, 1 and 2 or more) varied between 1.4 +/- 0.3, 3.0 +/-
      0.9 and 3.3 +/- 0.4 months, respectively (p = 0.028), and 1.4 +/- 0.2, 3.3 +/-
      0.2 and 3.5 +/- 2.6 months, respectively (p = 0.009). Twelve months after RPP
      84%, 66% and 82% of patients regained individual baseline urinary summary,
      function and bother scores, respectively. Postoperative radiation (XRT)
      represented the only independent predictor of the time to recover baseline
      urinary domain summary scores in a multivariate analysis (p = 0.042) with a
      median delay in the XRT (10 patients) and nonXRT group (82 patients) of 8.0 and
      6.7 months, respectively. CONCLUSIONS: Based on self-reported questionnaire data,
      a majority of patients regain urinary continence and urinary domain related QOL
      within 12 months after RPP. The time course of recovery from radical
      prostatectomy represents an important outcome criterion that should be shared
      with patients considering treatment options.

PMID- 14634421
TI  - Stage T1 renal cell carcinoma relapsing in the vagina 10 years after initial
      diagnosis.

PMID- 14634422
TI  - Mesonephroid adenocarcinoma of the bladder: a rare tumor in urology.

PMID- 14634423
TI  - Intraperitoneal bladder rupture and bowel injury from perirectal impalement.

PMID- 14634424
TI  - Penile entrapment in a plastic bottle.

PMID- 14634425
TI  - Magnetic resonance imaging in the diagnosis of seminal vesicle cysts and
      associated anomalies.

PMID- 14634426
TI  - Colic perforation as a complication of tension-free vaginal tape procedure.

PMID- 14634427
TI  - Umbilical endometriosis.

PMID- 14634428
TI  - Re: Predictors of lower pole renal stone clearance after extracorporeal shock
      wave lithotripsy.

PMID- 14634429
TI  - Re: Laparoscopic anatrophic nephrolithotomy: feasibility study in a chronic
      porcine model.

PMID- 14634430
TI  - Re: Laparoscopic radical nephrectomy: incorporating the advantages of hand
      assisted and standard laparoscopy.

PMID- 14634431
TI  - Re: Permanent interstitial brachytherapy for the management of carcinoma of the
      prostate gland. Re: Health related quality of life in men with prostate cancer.

PMID- 14634433
TI  - Re: Pretreatment total testosterone level predicts pathological stage in patients
      with localized prostate cancer treated with radical prostatectomy.

PMID- 14634434
TI  - Re: Randomized controlled trial of zoledronic acid to prevent bone loss in men
      receiving androgen deprivation therapy for nonmetastatic prostate cancer.

PMID- 14634435
TI  - Re: Mechanical and antibiotic bowel preparation for urinary diversion surgery.

PMID- 14634436
TI  - The epidemiology of congenital cryptorchidism, testicular ascent and orchiopexy.
AB  - PURPOSE: The frequency, significance and possible etiology of testicular ascent
      (acquired cryptorchidism) are characterized in light of the known incidence and
      natural history of congenital cryptorchidism, and data provided by longitudinal
      and epidemiological studies of ascended testes and orchiopexy rates. MATERIALS
      AND METHODS: We comprehensively reviewed the literature addressing the
      epidemiology of congenital and acquired cryptorchidism and orchiopexy. RESULTS:
      The incidence of congenital cryptorchidism in full-term males at birth (2% to 4%)
      and at age 1 year (approximately 1%) has not increased in the last few decades.
      The risk of ascent may be as high as 50% in cases where 1 testis is significantly
      retractile. Ascended testes are typically unilateral (77%), identified in mid
      childhood and located distal to the inguinal canal (77%). Ascended and
      significantly retractile testes may be prone to the same germ cell maldevelopment
      seen in congenital cryptorchidism. Cumulative orchiopexy rates in defined
      populations are 2% to 4%, and mean age at orchiopexy remains higher than expected
      (greater than 4 years), despite a long held standard of care that includes
      recommendation for surgery by age 2. These data suggest that cryptorchidism may
      be acquired in a significant subset of cases. CONCLUSIONS: With close monitoring
      of young boys spontaneous ascent of testes from a scrotal to a suprascrotal
      position may be observed with time, due to either true or apparent testicular
      ascent, with possible adverse effects on germ cell development and fertility
      potential. Patients with significant testicular retractility appear to be at
      highest risk for acquired cryptorchidism, and should be followed closely at
      yearly intervals until puberty.

PMID- 14634437
TI  - Successful renal transplantation in children with posterior urethral valves.
AB  - PURPOSE: The treatment of children with posterior urethral valve (PUV) and end
      stage renal disease can be challenging. Some series have had poor outcomes after
      renal transplantation with an increased risk of graft dysfunction and urinary
      tract infections. We present our experience with a pediatric population and
      compare it to all the other pediatric renal transplants done at our institution.
      MATERIALS AND METHODS: We identified 10 patients with PUV who underwent a total
      of 13 renal transplants between 1990 and 2000. The comparison group included 120
      transplants done in 95 patients during the same period. Cumulative allograft
      survival and function were recorded. RESULTS: Overall patient survival in the PUV
      group was 100%. Mean age at transplant in the PUV group was 10.0 years and mean
      followup was 3.9 years. Six patients underwent high proximal urinary tract
      diversion, while the remainder had primary transurethral valve ablation. Three
      patients had bladder augmentation before transplantation. Cumulative allograft
      survival in the PUV group at 1 and 5 years was 85% and 64%, respectively. Of the
      10 patients 9 currently have functioning living related donor transplants. One
      patient lost 3 cadaveric donor transplants to chronic rejection. No patients lost
      grafts due to infection or bladder dysfunction. Mean serum creatinine of the
      functioning grafts was 1.1 mg/dl. CONCLUSIONS: Renal transplantation can be
      performed safely and effectively in patients with PUV, including those who have
      undergone previous proximal urinary tract diversion. Preoperative bladder
      management and continued monitoring of bladder and kidney function
      postoperatively are paramount in the preservation of allograft function.

PMID- 14634438
TI  - Extracorporeal shock wave lithotripsy as first line treatment alternative for
      urinary tract stones in children: a large scale retrospective analysis.
AB  - PURPOSE: Management of urinary tract stones in children represents a challenging
      problem. In this study we retrospectively analyzed our experience with
      extracorporeal shock wave lithotripsy (SWL) in children. MATERIALS AND METHODS:
      During a 12-year period 408 urinary tract calculi in 344 children (mean age 8.7
      +/- 3.9 years, range 6 months to 14 years) were managed with the Lithostar Plus
      lithotriptor (Siemens Medical Systems, Iselin, New Jersey). There were 57
      caliceal stones, 167 in the renal pelvis, 31 in the proximal ureter, 16 in the
      mid ureter and 121 in the distal ureter, and 16 bladder stones. RESULTS: All
      patients were treated on an outpatient basis, with intravenous sedation being
      used in 138 (40.1%), general anesthesia in 132 (38.4%) and no anesthesia in 74
      (21.5%). A maximum of 3,500 shocks and 18 kV per session was given. A total of
      780 SWL sessions were applied (mean 1.9 sessions per stone). Overall, a stone
      free rate of 79.9% and clinically insignificant residual fragments in 13.2% of
      cases were observed at 3-month followup with a re-treatment rate of 53.9%.
      Overall efficacy quotient was 50.9%. Significantly more favorable results were
      achieved in ureteral calculi and stones 2 cm or smaller (p <0.05). Complications
      were observed in 33 patients (9.6%). CONCLUSIONS: Our results indicate that SWL,
      with satisfactory stone-free rates and efficacy quotients in stones 2 cm or
      smaller can be offered as a first line treatment in children.

PMID- 14634439
TI  - Long-term outcome of laparoscopically managed nonpalpable testes.
AB  - PURPOSE: We evaluated laparoscopic diagnostic findings in 108 impalpable testes,
      and analyzed the success rate and long-term outcome of either direct laparoscopic
      orchiopexy or the 2-stage Fowler-Stephens procedure. MATERIALS AND METHODS: A
      total of 84 children with 108 impalpable testes and a mean age of 1.9 years
      underwent laparoscopy between 1992 and September 2000. Long-term outcome with
      regard to viability and location of the testes was evaluated. RESULTS: Of the 108
      testes 72 were located intra-abdominally, of which 28 were managed by direct
      laparoscopic orchiopexy, 29 were managed by a 2-stage laparoscopic Fowler
      Stephens procedure and 15 were vanishing. The remaining 36 testes were inguinally
      located during exploration and orchiopexy, except for 5 vanishing testes. In all
      cases the operation proceeded as planned. After a mean followup of 6.2 years all
      laparoscopically managed testicles were in a normal scrotal position with normal
      perfusion as revealed by color flow Doppler sonography. Two testicles became
      atrophic after a 2-stage Fowler-Stephens procedure. Morbidity was low in all
      children. CONCLUSIONS: The laparoscopic approach allows not only diagnosis, but
      also adequate therapy regardless of whether direct orchiopexy or a 2-stage
      procedure is performed. Our long-term results clearly demonstrate that even in
      the patients undergoing the 2-stage procedure the laparoscopic approach is safe
      and efficient, and leads to excellent results concerning viability of the
      affected testicles. Progress and experience gained during recent years are
      encouraging in continuing laparoscopic procedures in children.

PMID- 14634440
TI  - Pediatric testicular tumors: contemporary incidence and efficacy of testicular
      preserving surgery.
AB  - PURPOSE: Testicular tumors in the pediatric population are fundamentally distinct
      from their adult counterparts. We reviewed a contemporary single series from a
      large pediatric health science center. We also examined our experience with
      testis conserving surgery and then used it to develop a preoperative management
      algorithm. MATERIALS AND METHODS: A retrospective review was performed of all
      testicular tumors at a single institution from 1984 to 2002. Data were compiled
      using the American Academy of Pediatrics testis tumor registry data collection
      form. We further examined partial orchiectomies for indications and outcomes with
      respect to cancer control and testicular viability. RESULTS: A total of 51
      primary testicular lesions were identified. Patient age was prenatal to 16 years
      with a scrotal mass the most common presentation (81%). Mature teratoma,
      rhabdomyosarcoma, epidermoid cyst, yolk sac and germ cell tumors accounted for
      43%, 26%, 10%, 8% and 6% of cases, respectively. This distribution was markedly
      different from the last reported American Academy of Pediatrics data base. Organ
      preserving surgery was planned and achieved in 13 cases. All surgeries were
      successful with respect to cancer control and testicular preservation.
      CONCLUSIONS: We believe that the higher incidence of teratoma is more
      representative of this population and yolk sac tumor is a minority diagnosis. The
      single institution review eliminates the interinstitutional referral
      heterogeneity that may have skewed larger data bases. Furthermore, the concept of
      testicular preserving surgery becomes an attractive option since we present its
      safety and efficacy. The management algorithm should facilitate the preoperative
      decision to perform less radical surgery and help preserve testicular tissue.

PMID- 14634441
TI  - Repeat spontaneous bladder rupture following radiation therapy.

PMID- 14634442
TI  - The Proteus syndrome associated with life threatening hematuria.

PMID- 14634443
TI  - Altered expression of interstitial cells of Cajal in congenital ureteropelvic
      junction obstruction.
AB  - PURPOSE: Peristaltic contractions in the upper urinary tract serve to move urine
      from the kidney through the ureter to the bladder. Ureteropelvic junction (UPJ)
      obstruction is the most common cause of congenital hydronephrosis in children. To
      our knowledge the pathophysiology of UPJ obstruction is unknown. C-kit positive
      interstitial cells of Cajal (ICCs) are pacemaker cells that facilitate active
      propagation of electrical events and mediate neurotransmission. We investigated
      the expression of c-kit positive cells in the muscle layer of normal and
      obstructed UPJ specimens. MATERIALS AND METHODS: A total of 19 human formalin
      fixed, paraffin embedded specimens of intrinsic UPJ obstruction from children
      with a mean age of 2.3 years (range 2 months to 12 years) and 7 control samples
      from children with a mean age of 4.5 years (range 11 months to 9 years) were
      investigated immunohistochemically for the expression of c-Kit oncoprotein and
      peripherin by light and laser scanning microscopy. Quantification of
      immunolabeled structures was quantified using computerized image analysis.
      RESULTS: Peripherin immunoreactivity was strong in the muscle layer of normal UPJ
      specimens, while in UPJ obstructed specimens there was a decrease in peripherin
      positive nerve fibers. In normal UPJ specimens there were many c-Kit positive
      ICCs between the muscle bundles. The density of ICCs was markedly decreased in
      the muscle layers of UPJ obstructed specimens. CONCLUSIONS: To our knowledge this
      study shows for the first time the immuno-expression of c-Kit positive ICCs in
      the proximal part of the normal human upper ureter. The altered density of c-Kit
      positive cells in UPJ obstruction may have a role in the failure of transmission
      of peristaltic waves across the UPJ.

PMID- 14634444
TI  - The intravesical ureter in children with vesicoureteral reflux: a morphological
      and immunohistochemical characterization.
AB  - PURPOSE: We investigated intravesical ureteral endings using immunohistochemical
      methods to study general morphology, smooth muscle architecture and collagen
      composition in children with vesicoureteral reflux. MATERIALS AND METHODS:
      Samples were obtained from 29 ureterorenal units in children with a mean age of
      52.3 months undergoing reflux surgery. Routine histological paraffin embedded
      sections were stained with hematoxylin and eosin, and Masson trichrome to assess
      general morphology. Staining for actin, myosin and desmin was performed to
      evaluate the presence, allocation and architecture of the ureteral smooth muscle
      wrap. In addition, indirect immunohistochemical methods were used to study the
      collagen composition of the ureteral wall and CD68 was used for macrophage
      labeling as a marker of tissue remnant scavenging. All investigations were done
      using high power field magnification for quantification. In addition, age
      matched, nonrefluxing ureteral specimens served as controls. RESULTS: Smooth
      muscle alpha-actin, myosin and desmin expression were extensively decreased in
      all specimens pertaining to the ureteral ending. This distal part showed a high
      degree of muscle atrophy and degeneration as well as a disordered fiber
      arrangement associated with increased extracellular matrix collagen accumulation.
      In addition, CD68 positive macrophages were significantly increased. In contrast
      to these observations, the proximal intravesical portion of the ureter showed
      intact morphology and arrangement of the muscular coat. CONCLUSIONS: Refluxing
      intravesical ureteral endings showed dysplasia, atrophy and architectural
      derangement of smooth muscle fibers. Consequently symmetrical contraction of the
      distal ureteral smooth muscle coat creating the active valve mechanism to protect
      reflux is not achievable.

PMID- 14634445
TI  - Female exstrophy: failure of initial reconstruction and its implications for
      continence.
AB  - PURPOSE: Bladder exstrophy is a rare malformation affecting only 1 female out of
      every 5 patients. In the female initial closure is combined with reconstruction
      of the outer genitalia, and urinary continence can be achieved by some girls
      without the need for later bladder neck reconstruction. We evaluated the
      management and outcome of failed initial closures in the female exstrophy
      population. MATERIALS AND METHODS: We performed a retrospective database review
      of patients with the exstrophy complex. Females with classic bladder exstrophy
      with failure of initial closure were identified. Age at initial closure, use of
      osteotomies, reasons for failure and number of closures, as well as definitive
      treatment and long-term outcomes were evaluated. RESULTS: Of 71 females with
      classic bladder exstrophy 14 had failure of initial closure. Of these patients 1
      had undergone initial closure at our institution and 13 were referred for
      reclosure. Mean followup was 6.5 years (range 3 to 12) and mean age was 10 years
      (4 to 14). The patients underwent a maximum of 3 closures (mean 2.4). Initial
      osteotomies were performed in 4 patients, no osteotomy in 8 and status was
      unknown in 2. Reason for initial failure was dehiscence in 11 patients and
      prolapse in 3. Five patients underwent a second closure elsewhere. On referral
      reclosure was successful using osteotomies in all patients. Bladder neck
      reconstruction was done in 5 patients (3 are daytime continent) and continent
      diversion in 4 (all are dry). The other patients are awaiting final treatment.
      CONCLUSIONS: The single most important step to achieve urinary continence is
      successful initial bladder and posterior urethral closure. Pelvic osteotomies
      ensure a tension-free closure and enhance bladder outlet resistance. Radical
      mobilization of the vesicourethral complex allows placement of the bladder deep
      within the pelvis. Failure of the initial closure in the female exstrophy
      population has a severe impact on long-term outcome and quality of life.

PMID- 14634446
TI  - Puberty does not induce serum antisperm surface antibodies in patients with
      previously operated cryptorchidism.
AB  - PURPOSE: We investigated serum antisperm surface antibody (ASA) prevalence at
      puberty, which is reported to be as high as 38% in the sera of males with
      cryptorchidism operated on before puberty. Operative technique impact, dartos
      pouch orchiopexy or testis fixation, was also examined. MATERIALS AND METHODS: We
      examined a total of 61 pubertal males (Tanner stage 2 or greater) divided into 3
      groups. Group 1 consisted of 24 males with cryptorchidism 10 to 17.9 years old
      who underwent unilateral dartos pouch orchiopexy before puberty (median age
      5.85). All of these cases were known to be negative for ASA preoperatively, and
      20 before puberty. Group 2 consisted of 22 males with cryptorchidism 12.1 to 17.7
      years old operated on previously (median age 10.35) by testicular fixation among
      other techniques. Group 3 consisted of 15 healthy males 12.2 to 17.3 years old.
      Prepubertal ASA status was unknown for groups 2 and 3. Operated testis was
      compared with counterpart before serum collection in group 1 and during operation
      in group 2. IgG IgM and IgA ASA were studied by the indirect Immunobead (BioRad,
      Clinisciences S.A., Montrouge, France) test. RESULTS: All sera tested were found
      negative in the 3 groups. Dartos pouch operation, testis fixation or even
      consecutive operations did not induce ASA production. Alterations in size or
      consistency were observed in operated testes in 10 patients in group 1, and in 8
      patients in group 2. CONCLUSIONS: Our results suggest that dartos pouch
      orchiopexy, testicular fixation and/or intrinsic developmental alterations of the
      cryptorchid testis does not elicit an autoimmune response against sperm surface
      antigens at puberty.

PMID- 14634447
TI  - Prescrotal orchiopexy: an alternative surgical approach for the palpable
      undescended testis.
AB  - PURPOSE: Inguinal exploration has been a standard approach for the management of
      palpable undescended testis. We performed prescrotal orchiopexy in patients with
      palpable undescended testes at our institution and we report our results.
      MATERIALS AND METHODS: We reviewed the charts of patients with palpable
      undescended testes treated with prescrotal orchiopexy from 1999 to 2002. All
      children were referred to a university children's hospital and 1 of 2 surgeons
      performed the procedures. Examination using anesthesia was performed prior to any
      incision. If the testis was palpable and could be drawn close to the scrotum,
      prescrotal orchiopexy was performed. Retractile testes were excluded. RESULTS:
      During this period 291 patients underwent orchiopexy. Prescrotal orchiopexy was
      performed in 78 patients. Followup was 1 to 36 months (median 6). The overall
      success rate was 98.8% and the overall complication rate was 4.7%. At 7 months
      postoperatively 1 patient had a palpable retractile testicle. One patient had
      wound hematoma and another patient had wound cellulitis. At 31 months of followup
      1 patient was considered to have a 25% decrease in testis size. All patients were
      without clinical evidence of hernia or hydrocele. CONCLUSIONS: Prescrotal
      orchiopexy is a successful procedure in select patients with a low complication
      rate. It has the advantage of a single, perfectly cosmetic incision. This
      approach should be considered an option when performing orchiopexy in a patient
      with a palpable, mobile undescended testis.

PMID- 14634448
TI  - Molecular pathways to prostate cancer.
AB  - PURPOSE: Prostate cancer continues to be a prevalent disease in the United States
      and western countries. Advances in the fields of molecular biology and genetics
      coupled with new developments in biotechnology have increased our understanding
      of events associated with the initiation and progression of prostate cancer. We
      reviewed recent scientific discoveries relating to genetic predisposition,
      somatic alterations and epigenetic phenomena involved in the pathogenesis of
      prostate cancer. MATERIALS AND METHODS: Reports published in the scientific
      literature with relevance to the molecular biology, genetics and epigenetics of
      prostate cancer were identified using the MEDLINE data base. Particular emphasis
      was placed on articles that investigated the contribution of somatic alterations
      to prostate cancer. RESULTS: A multitude of genes have recently been identified
      that are believed to be relevant to prostate carcinogenesis. A contemporary model
      for prostate cancer progression should include the potential contribution of
      inflammation to the development of preneoplastic or neoplastic lesions. Abnormal
      methylation of important growth regulatory or caretaker genes represents an
      alternative pathway to cancer in addition to aneuploidy, loss of heterozygosity
      and gene mutations. CONCLUSIONS: The identification of molecular markers specific
      to early and late events in prostate cancer progression is critical for the
      development of improved detection and prognostication strategies. While there is
      evidence to support the association between inflammation and prostate cancer, the
      exact mechanisms by which these processes occur are not well defined. The
      significant contribution of somatic and epigenetic defects to prostate
      carcinogenesis underscores the need to develop therapeutic approaches that
      specifically target these molecular alterations.

PMID- 14634449
TI  - Stem cell research: the facts, the myths and the promises.
AB  - PURPOSE: Stem cells, the potentially immortal cells capable of self-renewal, are
      the focus of research for the ultimate cure for degenerative diseases and the key
      to the mystery of human development and aging. No area of research since gene
      therapy has evoked so much enthusiasm and passionate debate as stem cell
      research. We present a glance of the current progress and controversies
      surrounding embryonic stem cells, and an overview of the evolving theory of
      potentially pluripotent adult stem cells. MATERIALS AND METHODS: We review and
      compare the literature on animal and human models that have provided the basis
      for significant research advances in recent years. The historical development and
      the most promising results to date are presented. RESULTS: The embryonic stem
      (ES) cell can differentiate into cells of all 3 germ cell layers. The therapeutic
      potential of the differentiated cells can modulate the symptoms of degenerative
      neurological disorders in animal models. However, the tumorigenic potential and
      ethical dilemma of human ES cell acquisition trouble many critics and have led to
      federal regulations on the development and use of human ES cells. Adult stem
      cells may provide an answer to circumvent these ethical issues and hold great
      promise for the future. CONCLUSIONS: While embracing the quest for advances in
      biomedicine, we cannot overlook the ethical responsibility to the patient and
      society. Regardless of the approach to harvest or culture stem cells human
      therapeutic application may still be years in the future.

PMID- 14634450
TI  - Activation of nitric oxide-cyclic guanosine monophosphate signaling in kidney by
      extracorporeal shock wave therapy.
AB  - PURPOSE: We defined whether extracorporeal shock wave therapy (ESWT) to the
      kidney activates the nitric oxide (NO)-cyclic 3',5'-guanosine monophosphate
      (cGMP) pathway. MATERIALS AND METHODS: A total of 90 male rabbits were randomly
      divided into group 1--pretreated with normal saline, group 2--pretreated
      intravenously (i.v.) with Nomega nitro-L-arginine-methyl ester (NAME) (100
      mg/kg), group 3--pretreated i.v. with NAME and L-arginine (300 mg/kg) with ESWT
      to 1 kidney, group 4--pretreated IV with ODQ (1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one) (20 microg/kg) and group 5--pretreated with normal saline
      with ESWT to the bladder. Plasma nitrite, NO metabolite and cGMP were analyzed in
      peripheral blood samples before, immediately after, and 30 and 60 minutes after
      ESWT. RESULTS: ESWT to the kidney but not to the bladder caused an increase
      before, immediately after, and 30 and 60 minutes after ESWT in plasma nitrite in
      group 1 (186.1 +/- 20.6, 217.5 +/- 21.6, 241.9 +/- 28.4 and 230.5 +/- 25.3 nM)
      and group 5 (149.0 +/- 14.7, 155.6 +/- 18.4, 131.8 +/- 13.6 and 140.0 +/- 15.7
      nM), and in cGMP in group 1 (24.2 +/- 1.9, 33.8 +/- 3.2, 32.9 +/- 2.2 and 29.4 +/
      1.9 pmol/ml) and group 5 (25.5 +/- 2.1, 27.5 +/- 2.5, 28.7 +/- 3.1 and 25.5 +/-
      2.6 pmol/ml, respectively). In group 2 NAME significantly inhibited the
      production of nitrite (113.4 +/- 18.6, 118.2 +/- 19.9, 114.6 +/- 18.3 and 112.5
      +/- 17.6 nM) and cGMP (19.4 +/- 2.6, 20.6 +/- 2.8, 19.3 +/- 2.7 and 18.6 +/- 2.6
      pmol, respectively). In group 3 inhibited nitrite and cGMP production caused by
      NAME was recovered with L-arginine. In group 4 ODQ significantly inhibited cGMP
      production. CONCLUSIONS: The results show that ESWT increases the level of NO and
      cGMP released by the kidney in an animal model.

PMID- 14634451
TI  - Increased DNA methyltransferase 1 protein expression in human transitional cell
      carcinoma of the bladder.
AB  - PURPOSE: DNA methylation is a key regulator of gene transcription and genomic
      stability, and alteration of DNA methylation is one of the most consistent
      epigenetic changes in human cancers. We elucidated the significance of aberrant
      protein expression of DNA methyltransferase (DNMT) 1, a major enzyme involved in
      the determination of genomic methylation patterns, during human urothelial
      carcinogenesis. MATERIALS AND METHODS: A total of 61 samples of normal
      urothelium, 89 noncancerous urothelium samples showing no remarkable histological
      changes from patients with bladder cancer (NBCs), 78 dysplastic urothelium
      samples and 174 transitional cell carcinoma samples (TCCs) were subjected to
      immunohistochemical analysis for DNMT1. RESULTS: The incidence of nuclear DNMT1
      immunoreactivity in NBCs (65%) was significantly higher than in normal urothelium
      (20%, p <0.0001) and the incidence was even higher in dysplastic urothelium
      samples (84%, p = 0.0017). The incidence of nuclear DNMT1 immunoreactivity was
      87% in TCCs and the intensity of nuclear immunoreactivity was markedly increased
      in TCCs compared with that in dysplastic urothelium samples. DNMT1 expression
      levels had already increased in NBCs in which the proliferating cell nuclear
      antigen labeling index had not yet increased. Increased DNMT1 protein expression
      correlated significantly with histological grade (p <0.0001). DNMT1 protein
      expression was higher in nonpapillary tumors (p = 0.0001), especially flat
      carcinoma in situ, than in papillary tumors. CONCLUSIONS: Progressively
      increasing expression of DNMT1 protein is not entirely a secondary result of
      increased cell proliferative activity, but rather it is associated with
      urothelial carcinogenesis even during the precancerous stages. In particular, it
      is associated with the development of flat carcinoma in situ, which is considered
      to be a precursor of nodular invasive carcinoma of the bladder.

PMID- 14634452
TI  - Optimal administration schedule of cisplatin for bladder tumor with minimal
      induction of metallothionein.
AB  - PURPOSE: The metal binding protein metallothionein (MT) confers drug resistance
      when MT is induced in tumor tissues. Cisplatin is known to induce MT synthesis in
      tumor tissues, which may lead to drug resistance. We examined whether a
      difference in the administration schedule of cisplatin affect the efficiency of
      MT induction. MATERIALS AND METHODS: Balb/c nude mice were inoculated with NMB-1
      human bladder tumor tissues and injected with cisplatin (total dose of 64
      micromol/kg) in a single injection or fractioned daily injections. Tumor MT
      concentration was determined 24 hours after the last injection of cisplatin by
      mercury binding assay. The effect of pretreatment with ZnCl2 on antitumor
      activity of cisplatin was examined in NMB-1 bearing mice. RESULTS: Tumor MT
      levels increased significantly with the increase in the number of cisplatin
      injections. Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2)
      caused the same level of MT induction (1.6-fold) as that of fractioned injections
      of cisplatin (4 x 16 micromol/kg). Pretreatment of NMB-1 bearing mice with ZnCl2
      (200 micromol/kg x 2) depressed cisplatin antitumor activity by about 50%.
      CONCLUSIONS: The induction of MT to a moderate extent (1.6-fold) in NMB-1 tumor
      inoculated in mice conferred cisplatin resistance. This level of MT induction can
      be achieved by fractioned daily injections of cisplatin but not by a single
      injection. Therefore, it is preferable to administer cisplatin as a single
      injection rather than as fractioned injections to achieve effective antitumor
      activity with minimum MT induction.

PMID- 14634453
TI  - Association between polymorphism of human oxoguanine glycosylase 1 and risk of
      prostate cancer.
AB  - PURPOSE: The human oxoguanine glycosylase 1 (hOGG1) gene encodes a DNA
      glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2
      deoxyguanine) from oxidatively damaged DNA. To determine whether hOGG1 has a role
      in the risk of prostate cancer we screened normal prostate tissue specimens for
      hOGG1 expression and assessed the role of hOGG1 Ser326Cys polymorphism in the
      risk of prostate cancer. MATERIALS AND METHODS: In 5 normal prostate tissues
      hOGG1 expression was determined by reverse transcriptase-polymerase chain
      reaction. The prevalence of hOGG1 Ser326Cys polymorphism was compared between
      white patients cases and controls using polymerase chain reaction restriction
      fragment length polymorphism analysis of genomic DNA isolated from 84 incident
      patients with primary prostate cancer and 252 individually matched controls (1:3
      ratio) by age (+/- 5 years at diagnosis) in white men. RESULTS: In all prostate
      tissues tested hOGG1 mRNA was detected. A significant association was found
      between hOGG1 genotypes and prostate cancer with a dose effect relationship
      (trend test p <0.003). A significantly increased risk of prostate cancer was
      observed for subjects with hOGG1(326Cys) allele (ORadj 2.1, 95% CI 1.2-3.8).
      CONCLUSIONS: These results suggest that hOGG1 may have a role in the repair of 8
      OH-dG adducts in prostate tissue and hOGG1 Ser326Cys polymorphism is associated
      with prostate cancer risk.

PMID- 14634454
TI  - Validity of computerized tomography in blunt renal trauma.
AB  - PURPOSE: Improved imaging techniques and new therapeutic possibilities require
      rethinking the indication for laparotomy with regard to blunt renal trauma.
      Refined classification systems would facilitate the decision relating to therapy
      but they are based on knowledge of the imaging accuracy of computerized
      tomography (CT). We evaluated the validity of the CT depiction of renal injuries.
      MATERIALS AND METHODS: A total of 42 porcine kidneys were subjected to
      traumatization of various degrees. They then underwent CT examination and were
      subsequently cross-dissected into slices 3 mm thick. The comparative evaluation
      involved 2,080 CT images and 1,819 macroscopic sectional views, which showed
      3,521 and 3,778 individual lesions, respectively. RESULTS: Using CT the overall
      extent of injury in renal trauma was only slightly overrated at an average of 15%
      higher than that seen on macroscopy. Simple linear lesions tended to be over
      assessed and parenchymal destruction tended to be under assessed. Central lesions
      were depicted more frequently than peripheral lesions. CT of medullary lesions
      and parenchymal detachment was not feasible. CONCLUSIONS: CT of the kidney
      enables the distinction of different kinds of lesions and their localization
      well. Pelvic structures or vessels can imitate linear lesions. However, this
      imaging procedure can be used as a basis for refining categorization systems for
      blunt renal trauma. It can also be used to obtain a large quantity of lesion data
      for biomechanical investigations.

PMID- 14634455
TI  - Creation of luminal tissue covered with urothelium by implantation of cultured
      urothelial cells into the peritoneal cavity.
AB  - PURPOSE: We established the culture condition of seeding urothelial cells onto a
      scaffold for implantation into the peritoneal cavity and evaluated the histology
      of implanted urothelial cells. MATERIALS AND METHODS: In part 1 of the study
      cultured porcine bladder urothelial cells were seeded onto 3 types of collagen
      gel made on microporous membrane, including collagen gel with or without cultured
      porcine bladder fibroblasts, or a feeder layer. The macroscopic and microscopic
      appearance of the gel with urothelial cells were examined in vitro. As an in vivo
      study, cultured porcine bladder urothelial cells were seeded onto a collagen
      gel/sponge matrix with or without cultured fibroblasts, or a feeder layer.
      Urothelial cell survival on each matrix was evaluated 28 days after implantation
      onto the omentum or mesentery of nude rats. In part 2 of the study rat urothelial
      cells were cultured and seeded onto fibrin gel/atelocollagen sponge matrix as an
      autologous implantation model. After 7 days of cultivation the matrix was folded
      with urothelial cells inside, implanted onto the mesentery and serially
      evaluated. RESULTS: Gel containing cultured fibroblasts was shrunken and basement
      membrane formation was observed on the gel with cultured fibroblasts or the
      feeder layer in vitro. Urothelial cells cultured with the feeder layer better
      survived on the collagen based matrix and formed a hollow-like lumen when
      implanted into the peritoneal cavity. The regenerated urothelium in an autologous
      implantation showed the same histological features as normal bladder urothelium.
      CONCLUSIONS: Selection of less degradable matrix and formation of basement
      membrane are critical for survival of implanted urothelial cells. The regenerated
      urothelium in an autologous implantation model seems to have the similar
      properties to the normal urothelium.

PMID- 14634456
TI  - Experimental autoimmune prostatitis: dihydrotestosterone influence over the
      immune response.
AB  - PURPOSE: In experimental autoimmune prostatitis in a rat model of chronic
      prostatic inflammation of noninfectious origin the prostatic 5alpha
      dihydrotestosterone (DHT) concentration decreases because of depressed 5alpha
      reductase activity. This decrease in androgens in situ could favor the
      development of autoimmune status at the same time. We noted that a DHT increase
      could protect the gland from immune aggression and/or its consequences in regard
      to prostatic androgenic metabolism. MATERIALS AND METHODS: We analyzed in vitro
      the (3H)-DHT enzymatic bioconversion of prostate homogenates of male accessory
      sexual gland extract (MAG) immunized rats and MAG immunized plus DHT implanted
      rats (DSG rats), and performed ventral prostate histological observations. The
      specific cell immune response against MAG antigen(s) was studied by delayed type
      hypersensitivity. RESULTS: In DSG and MAG rats, and controls enzymatic activities
      (3alpha/3beta-hydroxysteroid oxidoreductases) were 112.7 +/- 11.3, 91.4 +/- 15.0
      (not significant) and 147.0 +/- 12.8 pmol per minute per mg protein (p <0.025).
      Histological findings in DSG rat ventral prostates revealed infiltrating
      mononuclear cell foci in lower quantity and less magnitude than in MAG rat
      prostates. Delayed type hypersensitivity values were positive in MAG rats and
      lower in DSG rats in relation to kidney treated and untreated rats. CONCLUSIONS:
      Results suggest that constantly elevated DHT levels could decrease the cell
      immune response but not at significantly. In contrast, androgenic metabolism
      remains altered in the presence of exogenous androgens.

PMID- 14634457
TI  - Distribution and genetic association of putative uropathogenic virulence factors
      iroN, iha, kpsMT, ompT and usp in Escherichia coli isolated from urinary tract
      infections in Japan.
AB  - PURPOSE: Many virulence factors (VFs) have been reported in uropathogenic
      Escherichia coli. Recently we found a putative uropathogenic island including a
      gene encoding uropathogenic specific protein (USP). We have described the
      association between usp and other VFs reported previously. In the current study
      we examined epidemiological associations among 5 putative uropathogenic VFs.
      MATERIALS AND METHODS: In 427 E. coli strains, including 194, 76 and 107 isolates
      from patients with cystitis, pyelonephritis and prostatitis, respectively, and 50
      isolates from the stool of healthy adults, we detected catecholate siderophore
      receptor (iroN), iron regulated gene A homologue adhesin (iha), group II capsule
      (kpsMT) and outer membrane protease T (ompT) by polymerase chain reaction assays.
      We analyzed their distribution and genetic association. RESULTS: Relative
      prevalence ratios of iroN, iha, kpsMT, ompT and usp were 2.0 to 4.3 times more
      frequently in urinary tract infection isolates than in fecal isolates. Isolates
      from prostatitis were frequently associated with iroN, ompT and usp, whereas
      isolates from pyelonephritis frequently harbored usp. Together with iroN and iha
      we noted S-/F-fimbriae and iucD aerobactin (OR 95.9 and 187.2), while usp showed
      a close association with kpsMT and ompT (OR 38.3 and 38.4, respectively).
      CONCLUSIONS: Of the putative uropathogenic VFs examined iroN, iha, kpsMT, ompT
      and usp were frequently associated with urinary tract infection. Especially iroN
      and usp were most frequently associated with prostatitis. Some VFs were closely
      associated with a specific anatomical site of infection. Strong associations
      among several VFs might indicate not only well-known genetic linkages, but also
      unknown functional linkages among these VFs.

PMID- 14634458
TI  - Small adrenal glands in cats with feline interstitial cystitis.
AB  - PURPOSE: We documented the uncoupling of sympathetic nervous system activity from
      the hypothalamic-pituitary-adrenal axis in cats with feline interstitial cystitis
      (FIC). Altered hypothalamic-pituitary-adrenal activity was recently suggested in
      some humans with interstitial cystitis (IC) but to our knowledge no information
      exists on adrenal gland size and histopathology in this disease. To investigate
      further adrenal function in cats with FIC we determined cortisol responses to 125
      microg synthetic adrenocorticotropic hormone (ACTH) as well as adrenal size and
      histology. MATERIALS AND METHODS: ACTH stimulation studies were performed in 11
      healthy cats and 20 with FIC. Adrenal glands obtained at autopsy in 8 healthy
      cats and 13 with FIC were weighed, measured and examined histologically. RESULTS:
      Cats with FIC had significantly decreased responses to ACTH (2-way repeated
      measures ANOVA p <0.05). Mean weight +/- SD (58 +/- 50 vs 241 +/- 60 mg) and
      volume (264 +/- 72 vs 410 +/- 115 mm3) of adrenal glands were significantly
      smaller in cats with FIC than in healthy cats (p <0.05). CONCLUSIONS: These
      results suggest that cats with FIC may have mild primary adrenal insufficiency.
      Decreased adrenal size has been observed in patients with chronic fatigue
      syndrome, which can be a co-morbid condition in some patients with IC. If these
      abnormalities are confirmed in humans with IC, hormone replacement therapy may be
      indicated in select patients.

PMID- 14634459
TI  - Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of
      cyclophosphamide induced hemorrhagic cystitis in rats.
AB  - PURPOSE: We evaluated the relationship between nitric oxide and hyperbaric
      oxygenation in the pathogenesis and treatment of cyclophosphamide induced
      hemorrhagic cystitis in rats. MATERIALS AND METHODS: Cyclophosphamide (100 mg/kg)
      was injected in male Sprague-Dawley rats for cystitis induction. Animals were
      treated before and the day after cyclophosphamide injection with 100 mg/kg of the
      nitric oxide substrate L-arginine, 20 mg/kg of the nonselective nitric oxide
      synthase inhibitor L-NG-nitroarginine methyl ester and 20 mg/kg of the selective
      inducible nitric oxide synthase inhibitor S-methylisothiourea. Animals were
      exposed to hyperbaric oxygen (2.8 atmospheres absolute for 90 minutes twice
      daily) with or without the administration of L-arginine and nitric oxide synthase
      inhibitors. RESULTS: Cyclophosphamide injection resulted in severe cystitis. S
      methylisothiourea produced marked inhibition of cyclophosphamide induced bladder
      tissue damage. L-arginine and L-NG-nitroarginine methyl ester failed to a show
      meaningful protective effect. Hyperbaric oxygen protected the bladder only
      against ulceration. Moreover, hyperbaric oxygen did not contribute to the
      protective effects of L-arginine, L-NG-nitroarginine methyl ester or S
      methylisothiourea. CONCLUSIONS: Nitric oxide produced by inducible nitric oxide
      synthase is an important mediator in the pathogenesis of cyclophosphamide induced
      cystitis. Hyperbaric oxygen has a beneficial effect on repairing bladder damage
      rather than on bladder protection.

PMID- 14634460
TI  - Excitatory alpha1-adrenergic receptors predominate over inhibitory beta-receptors
      in rabbit dorsal detrusor.
AB  - PURPOSE: We mapped the regional distribution of alpha1 and beta-adrenergic
      receptors (ARs) in rabbit ventral and dorsal bladder, and characterized the
      alpha1-AR subtypes responsible for norepinephrine induced contraction of rabbit
      dorsal detrusor smooth muscle. MATERIALS AND METHODS: Responses to norepinephrine
      in the absence and presence of adrenergic antagonists were measured in strips
      taken from clearly defined regions of male rabbit ventral and dorsal bladder.
      RESULTS: In the absence of antagonists ventral strips from the bladder body
      relaxed in response to norepinephrine, while those from the ventral base
      contracted. Dorsal strips from the bladder dome also relaxed in response to
      norepinephrine but dorsal strips from the mid and lower body, and the base
      contracted. All contractile responses were antagonized by incubation with
      prazosin. Characterization of the alpha-AR subtypes present in dorsal strips from
      the mid and lower bladder body using BMY 7378 (8-[2-[4 to 2(-methoxyphenyl)-1
      piperazinyl]ethyl]-8-azaspiro [4,5] decane-7,9-dione dihydrochloride),
      chloroethylclonidine, 5-methylurapidil and WB 4101 (2-(2,6-dimethoxyphenoxyethyl)
      aminomethyl-1,4-benzodioxane) suggested that the alpha1-AR subtype responsible
      for the contraction is the alpha1A or alpha1L-AR. CONCLUSIONS: The male rabbit
      bladder contains at least 4 heterogeneous regions with differing functional
      responses to adrenergic stimulation, that is 1) the dorsal and ventral dome,
      where beta-ARs predominate, 2) the ventral detrusor, where beta-ARs predominate,
      3) the dorsal detrusor, where alpha1-ARs predominate, and 4) the dorsal and
      ventral bladder neck, where alpha1-ARs predominate.

PMID- 14634461
TI  - The functional role of beta-adrenoceptor subtypes in mediating relaxation of pig
      urethral smooth muscle.
AB  - PURPOSE: The predominant beta-adrenoceptor subtype present in the bladder and
      urethra is beta3-adrenoceptors. We investigated the role of beta-adrenoceptors in
      mediating relaxation of the in vitro female pig urethra. MATERIALS AND METHODS:
      Circular strips of urethral tissues were pre-contracted with KCl. Concentration
      relaxation curves (CRCs) to beta-adrenoceptor agonists were obtained in the
      absence and presence of antagonists. RESULTS: The nonselective beta-agonist
      isoproterenol in 30 animals and the beta3-adrenoceptor agonist BRL37344 in 4
      relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the beta2
      adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal
      relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol
      responses were 89.8% and 76.7%, respectively. Propranolol (10 to 100 nM) in 18
      animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6)
      but the Schild plot had a slope that was significantly less than unity (0.68, p
      <0.01). High concentrations of the beta1-antagonist CGP20712A (3 to 30 microM) in
      12 animals had no effect on responses to isoproterenol. The beta2-antagonist
      ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol
      with high affinity (apparent pKB 8.03) with a Schild slope not different from
      unity (0.79). The beta3-antagonist SR59230A (10 to 100 nM) in 12 animals
      antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild
      slope that was again significantly less than unity (0.62, p <0.01), indicating
      that responses to isoproterenol are mediated by more than 1 beta-adrenoceptor
      subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18
      animals competitively antagonized responses to salbutamol with high affinity (pA2
      8.5). CONCLUSIONS: In the pig urethra beta-adrenoceptor mediated relaxations to
      isoproterenol are mediated via beta2 and beta3-adrenoceptors, while responses to
      beta2-adrenoceptor agonists such as salbutamol appear to be mediated only via
      beta2-adrenoceptors.

PMID- 14634462
TI  - Analysis of the modifications in the composition of bladder glycosaminoglycan and
      collagen as a consequence of changes in sex hormones associated with puberty or
      oophorectomy in female rats.
AB  - PURPOSE: The effects of female sex hormones on rat vesical extracellular matrix
      were evaluated by analyzing glycosaminoglycan (GAG) and collagen composition
      under different hormonal conditions. MATERIALS AND METHODS: Bladders were
      obtained from Wistar rats, including young prepubertal females at age 30 days
      (YF), and adult intact females (AF), adult oophorectomized females (AOF), adult
      males and adult sham operated females at age 120 days. Oophorectomy and sham
      operation were performed at age 30 days. Bladders were analyzed for total GAG and
      collagen concentration per mg dry tissue and for the contents of GAG species, as
      determined by agarose electrophoresis and reported as the percent of total
      sulfated GAG. RESULTS: Collagen concentration in AF (54.80 +/- 4.60 microg/mg)
      was different from that in YF (34.52 +/- 5.29 microg/mg, p <0.001) and AOF (63.25
      +/- 3.51 microg/mg, p <0.001). GAG concentration in AF (0.71 +/- 0.18 microg/mg)
      was different from that in YF (0.45 +/- 0.07 microg/mg, p <0.001) and males (0.46
      +/- 0.10 microg/mg, p <0.001). The GAG species detected were dermatan sulfate and
      heparan sulfate. Dermatan sulfate content in AF (90.9% +/- 2.8%) was different
      from that in YF (86.6% +/- 2.4%, p <0.005), AOF (87.9% +/- 2.1%, p <0.005) and
      males (87.7% +/- 4.7%, p <0.005). Heparan sulfate content in AF was 9.1% +/-
      2.8%, which differed from that in YF (13.4% +/- 2.4%, p <0.025) and AOF (11.2% +/
      2.9%, p <0.025). CONCLUSIONS: Extracellular matrix of the female rat bladder
      undergoes marked remodeling during normal growth up to early adulthood with
      important consequences for vesical viscoelastic properties. Also, oophorectomy
      performed at a prepubertal age may lead to greater vesical wall stiffness.

PMID- 14634463
TI  - Y-27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic
      contraction of prostatic smooth muscle cells.
AB  - PURPOSE: Benign prostatic hyperplasia (BPH) causes mechanical urinary flow
      obstruction by 2 components, namely an enlarged prostate (static component) and
      elevated smooth muscle tone (dynamic component). Currently available treatments
      for BPH aim to inhibit the proliferation of prostatic cells or decrease the
      elevated tone. To our knowledge no single agent that can achieve these 2 ends has
      yet been identified. A specific inhibitor of Rho-kinase, Y-27632 ((+)-(R)-trans-4
      (1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride), has been
      demonstrated to cause smooth muscle relaxation and inhibit smooth muscle cell
      proliferation. Therefore, we investigated the effect of Y-27632 on prostatic
      smooth muscle proliferation and tone. MATERIALS AND METHODS: Rho-kinase
      expression was investigated by immunocytochemistry and immunoblotting in smooth
      muscle cells obtained from rat and human prostates. The effect of Y-27632 was
      examined on the proliferation of these cells and on the contractions elicited by
      electrical field stimulation and exogenous phenylephrine in rat prostatic strips.
      RESULTS: Immunoblot and immunofluorescence analysis showed that Rho-kinase is
      present in the cytosol and located in the perinuclear region in human and rat
      prostatic smooth muscle cells. Y-27632 decreased the proliferation of human and
      rat prostatic smooth muscle cells, and inhibited noradrenergic contractions
      elicited by electrical field stimulation and exogenous phenylephrine in rat
      prostatic strips (EC50 17.8 +/- 4.8 and 7.8 +/- 2.1 microM, respectively).
      CONCLUSIONS: To our knowledge we report the first demonstration of the presence
      of Rho-kinase in prostatic smooth muscle cells, and of the relaxant and
      antiproliferative effect of a Rho-kinase inhibitor. We suggest a novel use for
      Rho-kinase inhibitors in the treatment of BPH as a single agent with dual action.

PMID- 14634464
TI  - Rho-kinase inhibitors: potential therapeutics for benign prostate hyperplasia.

PMID- 14634467
TI  - Accuracy of cause of death determination without forensic autopsy examination.
AB  - Medical examiners and coroners commonly determine cause and manner of death
      without an autopsy examination. Some death certificates generated in this way may
      not state the correct cause and manner of death. From the case files of the
      Department of Forensic Medicine in Sydney, Australia, the authors retrospectively
      reviewed investigative information of all cases in a 6-month period that were
      initially considered natural deaths (429). The authors, blinded to autopsy
      results, accepted 261 cases as appropriate for certification without autopsy and
      assigned a cause of death to each. Per standard local practice, all cases had
      been autopsied. The actual causes of death as determined by autopsy were then
      revealed and compared with the presumed causes of death. Most presumed and actual
      causes of death were cardiovascular (94% and 80%, respectively). The majority of
      presumed causes of death were listed as ASCVD as the cases lacked features of a
      more specific cardiovascular process. A large majority of cases had a presumed
      cause of death of ischemic heart disease based on individual case details. The
      actual causes of death demonstrated a large breadth of cardiovascular and
      noncardiovascular disease processes, even though ischemic heart disease accounted
      for 62% of deaths. The presumed cause of death was completely wrong in 28% of
      cases. A nonnatural manner of death was present in 3% of cases. This study
      demonstrates that experienced forensic pathologists may generate erroneous death
      certificates for cases that are not autopsied.

PMID- 14634468
TI  - Pericarotid bone splinter: a microscopic appearance in hanging.
AB  - The investigation of the neck structures drawn from 145 cases of asphyxia
      involving pressure on the neck, for which microscopic examination was required at
      the Pathology Laboratory of the "Hotel Dieu" Hospital from Lyon, France, during
      January 1, 1999, to May 1, 2001, has pointed out in 3 cases, besides the classic
      signs already known, a particular lesion unmentioned yet in the literature,
      namely, a pericarotid bone splinter, placed in the proximity of the common
      carotid artery bifurcation. The bone splinters had dimensions between 0.25 and
      0.7 mm and a certain antemortem character, surrounded by hemorrhagic areas and by
      fibrin. The 3 cases deal with adult males who had died through complete hanging,
      with the knot placed lateral, the hanging mark having the maximum depth in the
      laterocervical region, correspondent with our finding. Given the location of the
      bone splinter, we believe that this was produced by the tearing out from the
      transverse apophysis of the fourth cervical vertebra, as a consequence of the
      sudden traction during hanging. This sign appeared neither at other types of
      hanging nor at strangulation by hand or by ligature.

PMID- 14634469
TI  - Sex determination from the talus of South african whites by discriminant function
      analysis.
AB  - The field of forensic anthropology involves the building of an antemortem profile
      of an individual from skeletal remains. This includes sex and race determination
      and age and stature estimation. Since most bones that are conventionally used for
      sex determination are often recovered either in a fragmented or incomplete state,
      it has become necessary to use denser bones that are often recovered intact, eg,
      the patella, calcaneus, and talus. Thus the aim of this study is to assess the
      sex-determining ability of each of the measurements of the talus and derive
      discriminant function equations for sex determination in the South African white
      population. Sixty male and 60 female tali of South African whites obtained from
      the Raymond A. Dart Collection of Human Skeletons were used. Nine measurements
      were taken on each talus. Descriptive statistics and discriminant function
      analysis were performed on the acquired data. The basic statistics showed that
      all measurements were sexually dimorphic. Univariate, stepwise, and direct
      discriminant function equations were generated for use in sex determination. The
      level of average accuracy of sex classification was 80% to 82% for the univariate
      method, 85% to 88% for the stepwise method, and 81% to 86% for the direct method.
      It is concluded that the talus of South African whites is useful for sex
      determination.

PMID- 14634470
TI  - Etiology of pulmonary thromboembolism in the absence of commonly recognized risk
      factors.
AB  - Pulmonary thromboembolism is an often fatal complication of venous thrombosis.
      Any component or combination of the components composing Virchow's triad
      (venostasis, hypercoagulability, and endothelial damage) increases the propensity
      for a thrombophilic state. Hypercoagulable states may be inherited or acquired.
      While the etiology in many cases may be evident either on physical examination or
      on evaluation of the decedent's medical history, this is often not the case. We
      conducted a retrospective study of cases presenting to the Jefferson County
      Coroner/Medical Examiner's Office in Birmingham, Alabama, who were given a
      diagnosis of pulmonary embolism. A search of cases within the past 23 years
      yielded 81 cases. An underlying cause was determined in 70 cases (86%). The
      remaining 11 (14%) cases had no identifiable cause. We believe that a number of
      these cases may represent an underlying thrombophilic disorder. Since these
      disorders may be of an inherited or acquired nature, the determination of an
      etiology may be relevant to the decedent's family. Postmortem blood analyses may
      in selected cases be useful and appropriate for the detection of some of these
      disorders. However, such analyses are not practical in all cases, with each case
      having to be evaluated on its own merits.

PMID- 14634471
TI  - Deaths among criminal suspects, law enforcement officers, civilians, and prison
      inmates: a coroner-based study.
AB  - During the interaction between a criminal suspect and a law enforcement officer,
      the risk of death to the suspect, police, or civilians is increased.
      Unfortunately, very little information is available on the death risks arising
      from this interaction. This study provides an assessment of the risk of death to
      law enforcement officers, suspects, and bystanders by separating the interactions
      into the following 4 phases: (1) events prior to and during arrest; (2) police
      pursuits or chases; (3) transport of the suspects; and (4) during incarceration.
      A 5-year (1994-1998) retrospective coroner-based study of all deaths that
      occurred during these 4 phases was conducted in Allegheny County, Pennsylvania. A
      total of 77 cases were identified; 14 deaths (18.1%) occurred prior to or during
      arrest, 10 (12.9%) during police chases, 2 (2.6%) occurred while the actors were
      being transported, and 51 (66.2%) during incarceration. The majority of cases
      (98.7%) were males, blacks (63.6%), and single (50.6%). The respective risks of
      death by phase were prearrest/arrest, 6.5 per 100,000 arrests; transport, 0.93
      deaths per 100,000 arrests; and incarceration, 268 deaths per 100,000 inmates.
      Study showed the following: (1) risk of death to offenders was greatest during
      police pursuits; (2) the risks during arrests are not insignificant and involved
      an officer being threatened with a weapon in one-third of the events; and (3)
      deaths among inmates were primarily due to natural causes.

PMID- 14634472
TI  - The correlation between skull fractures and intracranial lesions due to traffic
      accidents.
AB  - In this study, it was aimed to investigate the relationship between skull
      fractures and intracranial lesions following head injury. For this purpose, 500
      cases, which were referred to the Third Committee of Council of Forensic Medicine
      in Istanbul due to traffic accidents by the courts of laws between 1998 and 2000,
      were examined retrospectively. They were categorized in 3 groups based on
      findings of their cranium x-rays and brain tomographies. 1- The cases who have
      fractures in skull bones with brain lesions 2- The cases who have fractures in
      skull bones with no brain lesions 3- The cases who have brain lesions with no
      skull fractures. They were examined in detail according to age, sex, localization
      of skull fractures and brain lesions, and if surgery was applied or not. Of the
      cases, 152 (30.4%) had only linear fractures, 69 (13.8%) had depressed fractures,
      92 (18.4%) had linear fractures plus intracranial lesions, 49 (9.8%) had
      depressed fractures plus intracranial lesions and 138 (27.6%) had only
      intracranial lesions. The rate of intracranial lesion among the cases with the
      skull fracture was 38.9% (141/362), while the rate of skull fracture among the
      cases with the intracranial lesion was 50.3% (141/279) (P < 0.001). Male to
      female ratios were 2.4/1 for linear fractures, 5.2/1 for depressed fractures, and
      3.5/1 for intracranial lesions. Linear fractures were more frequent among females
      whereas depressed fractures were often among males (chi2: 9.68, df: 4, p: 0.046).
      The mean age was 26.3. The rate of depressed fractures was higher the age groups
      of 0-30 years. (chi2: 16.28, df: 4, p: 0.003). Depressed fractures in the regions
      of frontal and parietal and, linear fracture in the regions of temporal and
      occipital were found at higher rates (P < 0.001). In conclusion, we reviewed
      skull fractures and/or intracranial lesions due to traffic accidents, and found
      depressed fractures to be more common among males whereas linear fractures to be
      more common among females and young males. In the male, the skull architecture is
      thicker and stronger than females and young males. We can state that presence of
      skull fractures lowers the incidence of intracranial lesions by lowering the
      intracranial pressure.

PMID- 14634473
TI  - The medical review officer: a potential role for the medical examiner.
AB  - Drug use in the workplace is a problem, both in terms of public health and
      expense. Workplace drug testing programs serve as deterrents to drug use. Model
      programs, such as that of the Department of Transportation, use urine screening
      and are federally regulated or follow federal standards. An essential participant
      in this process is the medical review officer (MRO), a licensed physician who
      interprets the laboratory results generated from a workplace drug testing
      program. As a result of their training and experience with toxicology, collection
      of evidence, testimony, and recognition of the physical signs of drug abuse,
      medical examiners and forensic pathologists are well suited to serve as MROs.
      Recent regulations require the completion of training courses and MRO
      certification as prerequisites for participation in federal drug testing
      programs. Several courses are available to train physicians to participate as
      MROs.

PMID- 14634474
TI  - Death during transforaminal epidural steroid nerve root block (C7) due to
      perforation of the left vertebral artery.
AB  - Treatment for individuals suffering from migraines and pain due to an
      inflammation or impingement of a nerve range from noninvasive methods such as
      massage, physical therapy, and medications to invasive methods such as epidural
      steroid injections and surgery. Each method of treatment has an associated level
      of risk. While minor to moderate complications from such procedures do occur,
      deaths are very rare. We report the first cited case of a death associated with
      the pain management procedure called nerve root block, also referred to as a
      transforaminal epidural steroid injection. We present the medical history and
      autopsy findings of a 44-year-old white female who died of massive cerebral edema
      secondary to the dissection of the left vertebral artery and subsequent
      thrombosis due to the perforation of that artery by a 25-gauge spinal needle
      during a C-7 nerve root block.

PMID- 14634475
TI  - Unsuspected meningoencephalitis in a case of assault by blunt force trauma.
AB  - Reported is a case of an assault causing extensive blunt force injuries in which
      the clinical, radiologic, and postmortem findings were all consistent with death
      resulting from brain damage arising from the assault. The assailant was charged
      with murder. Subsequent full neuropathologic (including histologic) examination
      revealed the unsuspected finding of a widespread meningoencephalitis but no
      evidence of significant traumatic brain damage. The contributions of the
      infective process and of the trauma to death were felt to be unclear and a guilty
      plea to attempted murder was accepted. This case highlights the importance of a
      full neuropathologic examination, including histology, in cases of trauma to the
      head, even when the cause of death may initially appear obvious.

PMID- 14634476
TI  - Suicidal asphyxiation by using pure helium gas: case report, review, and
      discussion of the influence of the internet.
AB  - Suffocation by inhaled gases has been reported involving a variety of gases. We
      report a case of suicidal asphyxiation by forced replacement of oxygen with
      helium by using a complex homemade mask. In this case, a young woman researched
      suicide on the Internet and found an advocated method of suicide using helium. To
      our knowledge, there is only 1 previously reported case of suicidal asphyxia by
      using helium.

PMID- 14634477
TI  - Death following atypical compression of the neck.
AB  - The authors present 3 cases of asphyxia caused by atypical compression of the
      neck by the metal bed bars fitted at the sides of the bed to prevent falling out.
      These occurred in 3 elderly women living in nursing homes, confined to bed by
      severe neuropsychiatric disturbances. In all 3 cases, the minor nature of the
      skin lesions and absence of blood infiltrations in the anatomic structures of the
      neck had made it difficult to diagnose the cause of death. Inspection of the rest
      homes, together with the autopsy findings (acute pulmonary emphysema,
      conjunctival petechiae, and dark, fluid blood), enabled identification of
      asphyxia as the cause of death and its causal agent as the bed bars.

PMID- 14634478
TI  - Sudden death due to atlantoaxial subluxation in marfan syndrome.
AB  - Marfan syndrome is 1 of the commonest inherited connective tissue disorders.
      Sudden death may occur and is usually attributed to cardiovascular manifestations
      of the syndrome. Atlantoaxial hypermobility, increased odontoid height, and
      rotatory subluxation are well described in this syndrome, but this paper details
      what seems to be the first reported case of sudden and unexpected death due to
      spontaneous atlantoaxial subluxation in Marfan syndrome.

PMID- 14634480
TI  - Prothrombin G20210A mutation and sudden death.
AB  - The authors present a case of sudden death in a previously healthy 36-year-old
      male. At autopsy there were bilateral pulmonary thromboemboli and right
      ventricular dilatation. Histologic findings in the lungs included recanalized,
      old thrombi and evidence of pulmonary hypertension. Genetic analysis for
      hereditary risk factors was heterozygous positive for the prothrombin G20210A
      mutation. Implications of this finding, its history and the diagnostic technique
      shall be discussed. The authors recommend that all cases of deep venous
      thromboses and pulmonary thromboemboli lacking known risk factors be evaluated
      for newly described genetic variations associated with an increased risk for
      venous thrombosis.

PMID- 14634479
TI  - Delayed sudden death in an infant following an accidental fall: a case report
      with review of the literature.
AB  - Several controversies exist regarding ultimately lethal head injuries in small
      children. Death from short falls, timing of head injury, lucid intervals,
      presence of diffuse axonal injury (DAI), and subdural hematoma (SDH) as marker of
      DAI are the most recent controversial topics of debate in this evolving field of
      study. In this area of debate, we present a case of delayed death from a
      witnessed fall backwards off a bed in a 9-month-old black male child who struck
      his head on a concrete floor and was independently witnessed as "healthy"
      postfall for 72 hours until he was discovered dead in bed. Grandmother,
      babysitter, and mother all independently corroborated under police investigation
      that the child "acted and behaved normally" after the fall until death. Autopsy
      showed a linear nondisplaced parietal skull fracture, diastasis of adjacent
      occipital suture, subgaleal hemorrhage with evidence of aging, small posterior
      clotting SDH, marked cerebral edema, and a small tear of the midsuperior body of
      the corpus callosum consistent with focal axonal injury (FAI). No DAI was seen,
      and there were no retinal hemorrhages. All other causes of death were excluded
      upon thorough police and medical examiner investigation. Although this seems to
      be a rare phenomenon, a delayed, seemingly symptom-free interval can occur
      between a clinically apparent mild head injury and accidental death in a young
      child.

PMID- 14634483
TI  - Decreased proopiomelanocortin mRNA in lymphocytes of chronic alcoholics after
      intravenous human corticotropin releasing factor injection.
AB  - BACKGROUND: Alcohol abuse may involve an altered neuroendocrine response that
      mediates lymphocyte-derived proopiomelanocortin (POMC) production and
      inflammation. We investigated POMC messenger RNA (mRNA) expression in human
      lymphocytes ex vivo and their relation to plasma ACTH and immunoreactive beta
      endorphin (IR-beta-EP) after intravenous injection of human corticotropin
      releasing factor (hCRF) in chronic alcoholics (n = 12) and nonalcoholics (n = 12)
      before surgery. Lipopolysaccharide-stimulated interleukin (IL)-1 receptor
      antagonist (IL-1 Ra) as a marker for chronic inflammation was determined.
      METHODS: Chronic alcohol abuse was diagnosed according to DSM-IV criteria and
      alcohol consumption >60 g/day. A reverse transcription-polymerase chain reaction
      method with total RNA and subsequent solid phase minisequencing was used to
      quantify lymphocytic POMC mRNA after intravenous hCRF injection. Plasma ACTH,
      cortisol, and lipopolysaccharide-stimulated IL-1 Ra of monocytes were measured by
      enzyme-linked immunosorbent assay, and plasma IR-beta-EP was measured by using
      radioimmunoassay. RESULTS: Baseline values of POMC mRNA content in lymphocytes
      and IL-1 Ra of chronic alcoholics were significantly increased compared with
      nonalcoholics (p < 0.01). Thirty minutes after intravenous hCRF injection, a
      significant increase of lymphocytic POMC mRNA was measured (p < 0.05) in
      nonalcoholics, whereas in chronic alcoholics a significant decrease was observed
      (p < 0.05). CONCLUSIONS: Chronic alcoholic patients had an altered neuroendocrine
      immune axis before intravenous hCRF administration and were not able to adjust to
      intravenous CRF injection by increasing lymphocytic POMC mRNA expression.

PMID- 14634484
TI  - Sensitivity to ketamine, alone or in combination with ethanol, is altered in mice
      selectively bred for sensitivity to ethanol's locomotor effects.
AB  - BACKGROUND: Sensitivity to erthanol's locomotor activating and reinforcing
      effects may be influenced by some common neural mechanisms. Mice selectively bred
      in replicate for increased (FAST-1 and FAST-2) and decreased (SLOW-1 and SLOW-2)
      sensitivity to ethanol's locomotor stimulant effects are useful for investigating
      the neural substrates of ethanol's effects. Previous studies have suggested that
      differences in N-methyl-d-aspartate (NMDA) receptors may underlie differences in
      ethanol-induced locomotion in these mice. This study examined the responses of
      FAST and SLOW mice to ketamine, a fast-acting NMDA antagonist. In addition,
      reverse-selected lines (r-FAST-1, r-FAST-2, r-SLOW-1, and r-SLOW-2) were tested
      as a means of verifying correlations detected in the forward-selected lines. Two
      initial studies characterized ketamine-induced locomotion in DBA/2J (D2) mice, an
      inbred strain chosen for its high sensitivity to ethanol-induced locomotion.
      METHODS: After a 2- to 3-day period of habituation to test procedures, mice were
      given intraperitoneal injections of ketamine alone (0, 5, 10, 20, 30, and 60
      mg/kg) or in combination with 1 or 2 g/kg ethanol. Locomotor activity was
      measured for 20 to 30 min in automated activity monitors. RESULTS: When
      administered alone, ketamine dose-dependently stimulated the locomotor activity
      of D2 mice and also reduced the amount of ethanol-induced stimulation. Ketamine
      stimulated locomotion more in FAST mice than in SLOW mice. Reverse selection
      abolished these differences, because r-FAST and r-SLOW mice did not differ in
      their responses to ketamine. Ketamine potentiated ethanol's locomotor effects
      within FAST mice and potentiated ethanol's locomotor depressant effect within one
      replicate of SLOW mice. CONCLUSIONS: We propose that sensitivities to ethanol-
      and ketamine-induced locomotion are genetically correlated and that the combined
      effects of ethanol and ketamine in FAST mice reflect a leftward shift in
      ethanol's biphasic dose-response curve.

PMID- 14634485
TI  - Analyses of quantitative trait loci contributing to alcohol preference in
      HAD1/LAD1 and HAD2/LAD2 rats.
AB  - BACKGROUND: The high-alcohol-drinking (HAD1/HAD2) and low-alcohol-drinking
      (LAD1/LAD2) rat lines, derived from the N/NIH rat, were developed by using a
      within-family selection and rotational breeding design for alcohol preference and
      alcohol consumption. Previously, a 20-cM genome screen identified quantitative
      trait loci (QTLs) on chromosomes 5, 10, 12, and 16 by using F2 progeny from HAD1
      and LAD1 animals. METHODS: A total of 459 F2 HAD1 x LAD1 animals had been
      previously genotyped, and 428 HAD2 x LAD2 F2 animals were genotyped for
      microsatellite markers within the identified QTL regions. Linkage analyses were
      performed with the program QTL Express, a recently developed Web-based interface
      that implements a least-squares method. RESULTS: The linkage peaks previously
      identified in the HAD1 x LAD1 genome scan relied on one or two markers. Placement
      of additional markers in and around the QTL regions provided further support for
      each of the QTLs. Two of the QTLs on chromosomes 10 and 16 were confirmed in the
      replicate line; these QTLs exhibited linkage in both the HAD1/LAD1 and HAD2/LAD2
      studies. CONCLUSIONS: This study demonstrated the importance of confirmation of
      QTLs in a replicate line, as well as the complexity of the genetic contribution
      to alcohol preference. Assessing these QTL regions in the inbred HAD/LAD animals
      will further facilitate characterization of these regions.

PMID- 14634486
TI  - Effect on plasma insulin and plasma glucose of consuming white wine alone after a
      meal.
AB  - BACKGROUND: Rodent studies have highlighted the possibility that alcohol may
      promote a significant decrease in the level of glucose-stimulated plasma insulin
      concentration. The aim of this study was to investigate whether a similar alcohol
      induced decrease in plasma insulin occurs in humans, by assessing the level of
      plasma insulin and plasma glucose when a moderate amount of commercially
      available bottled white wine is consumed alone after a meal. METHODS: Eight
      nondiabetic men aged 19 to 22 years participated in this investigation.
      Participants were required to consume some food for 45 min before ingesting three
      standard units of white wine (30 g of alcohol) over 90 min. Plasma insulin and
      plasma glucose levels were assessed at regular 45-min intervals across the
      experimental period. RESULTS: The data showed a significant alcohol-induced
      decrease in the level of plasma insulin and a nonsignificant trend for a decrease
      in plasma glucose concentration in all participants after 15 g of alcohol had
      been consumed alone after a meal. CONCLUSIONS: These findings highlight the
      possibility that white wine, if consumed alone after a meal, may significantly
      alter energy utilization and possibly cause an alteration in glucose metabolism.

PMID- 14634487
TI  - The neurotoxicity induced by ethanol withdrawal in mature organotypic hippocampal
      slices might involve cross-talk between metabotropic glutamate type 5 receptors
      and N-methyl-D-aspartate receptors.
AB  - BACKGROUND: We recently reported that the sodium salt of acamprosate (Na
      acamprosate) demonstrates the characteristics of an antagonist at metabotropic
      glutamate type 5 receptors (mGluR5s) rather than at N-methyl-d-aspartate
      receptors (NMDARs). Because mGluR5s are able to enhance the function of NMDARs,
      this interplay may be involved in the dysregulation of glutamatergic transmission
      during ethanol withdrawal. The following studies use organotypic hippocampal
      slice cultures at a mature age to investigate the potential for this interplay in
      the neurotoxicity associated with withdrawal from long-term ethanol exposure.
      METHODS: At 25 days in vitro, organotypic hippocampal slice cultures prepared
      from male and female 8-day-old rats were exposed to an initial concentration of
      100 mM ethanol for 10 days before undergoing a 24-hr period of withdrawal. The
      effects of Na-acamprosate; 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893), a
      noncompetitive antagonist at mGluR5s; 7-(hydroxyimino)cyclopropa[b]chromen-1a
      carboxylate ethyl ester, a noncompetitive antagonist at mGluR1s; dizocilpine (MK
      801), a noncompetitive NMDAR antagonist; and staurosporine on the neurotoxicity
      induced by ethanol withdrawal were assessed by determining differences in
      propidium iodide uptake. Polypeptide levels of mGluR5s and the NR1 and NR2B
      subunits of NMDARs were also determined via Western blot analyses after 10 days
      of ethanol exposure. RESULTS: Significant neurotoxicity was always evident in the
      CA1 hippocampal region after a 24-hr withdrawal period. This spontaneous
      neurotoxicity resulted from intrinsic changes induced by the long-term presence
      of ethanol. Na-acamprosate (200-1000 microM), SIB-1893 (200-500 microM), MK-801
      (20 microM), and staurosporine (200 nM) were all neuroprotective. The polypeptide
      levels of mGluR5s and NR1 and NR2B subunits of NMDARs were all increased after
      ethanol exposure; however, the increase in mGluR5s did not achieve statistical
      significance. CONCLUSIONS: From this model of long-term ethanol exposure and
      withdrawal, the functional interplay between mGluR5s and NMDARs might represent a
      novel target for the prevention of neurotoxicity associated with ethanol
      withdrawal.

PMID- 14634488
TI  - Fyn kinase and NR2B-containing NMDA receptors regulate acute ethanol sensitivity
      but not ethanol intake or conditioned reward.
AB  - BACKGROUND: The tyrosine kinase Fyn previously has been shown to play a key role
      in mediating acute tolerance to ethanol. Recently, we found that the
      compartmentalization of Fyn to the NR2B subunit of the NMDA receptor (NMDAR) in
      the hippocampus regulates Fyn phosphorylation of NR2B in response to ethanol,
      which mediates the acute tolerance of NMDAR to ethanol inhibition in hippocampal
      slices. In this study we determined, first, whether acute tolerance to ethanol
      inhibition is mediated via NR2B-containing NMDARs in vivo and, second, whether
      the increase in acute sensitivity to ethanol in the Fyn-/- mice influences
      ethanol consumption or ethanol's conditioned rewarding effects. METHODS: A loss
      of righting reflex test was used to study the acute/sedative effects of ethanol
      after intraperitoneal injections of sedative doses of ethanol. Conditioned place
      preference was used to study the rewarding properties of ethanol. The two-bottle
      choice protocol was used to measure oral ethanol self-administration and
      preference as described previously. RESULTS: We found that systemic injection of
      the NR2B-containing NMDAR selective antagonist, ifenprodil, abolished the
      differences between Fyn+/+ and Fyn-/- mice in sensitivity to the acute sedative
      effects of ethanol. Moreover, we found that Fyn-/- and Fyn+/+ mice did not differ
      in their voluntary ethanol consumption or in the rewarding properties of ethanol.
      CONCLUSIONS: Our results suggest that the interaction between Fyn and NR2B
      mediates the acute sedative effects of ethanol, and that alteration in acute
      ethanol sensitivity does not necessarily correlate with levels of ethanol
      consumption or the rewarding properties of ethanol.

PMID- 14634489
TI  - Family history of alcoholism and response to sweets.
AB  - BACKGROUND: The relationship between a hedonic response to sweet tastes and a
      propensity to excessive alcohol drinking is supported by both animal and human
      studies. This study was designed to test the hypothesis that the genetic risk for
      alcoholism as measured by a paternal history of alcoholism in young social
      drinkers is associated with sweet-liking, defined as rating the strongest offered
      sucrose solution (i.e., 0.83 M) as the most palatable during the standard sweet
      test. METHODS: Participants were 163 subjects (39% male) without a lifetime
      history of alcohol or drug abuse or dependence. Eighty-one subjects had a
      paternal history of alcoholism (FH+), and 82 did not (FH-). Each subject rated a
      series of sucrose solutions for intensity of sweetness and palatability. Subjects
      were categorized as sweet-likers if they rated the highest sucrose concentration
      as the most pleasurable. RESULTS: The estimated odds of being a sweet-liker were
      2.5 times higher for FH+ than for FH- subjects. FH+ subjects disliked the tastes
      of the two weakest offered sucrose concentrations (0.05 and 0.10 M), whereas FH-
      subjects reported these tastes to be neutral. CONCLUSIONS: The results of this
      study support the hypothesis that sweet-liking is associated with a genetic
      vulnerability to alcoholism.

PMID- 14634490
TI  - Do college students drink more than they think? Use of a free-pour paradigm to
      determine how college students define standard drinks.
AB  - RATIONALE: Much of what is known about college drinking comes from self-report
      survey data. Such surveys typically ask students to indicate how many drinks they
      consume within a given period of time. It is currently unclear whether college
      students and researchers use similar operational definitions of a single drink.
      This information is critical given the widespread reliance on survey data for
      assessing the correlates and consequences of college drinking. OBJECTIVES: This
      study investigated whether college students define standard drink volumes in a
      way that is consistent with the operational definitions commonly used by
      researchers. METHODS: Students (n = 106) were administered an alcohol survey and
      then asked to perform three tasks. The tasks involved free-pouring fluid into
      empty cups of different sizes and estimating the volume of a single beer, a shot
      of liquor, or the amount of liquor in a mixed drink. The volumes poured by
      students then were compared with standards used in a well-known nationwide survey
      (i.e., 12 oz of beer and 1.25 oz of liquor in a shot or mixed drink). RESULTS: In
      every cup size of every task, students overestimated how much fluid they should
      pour to create a standard drink. In all three tasks, the magnitude of the
      discrepancy increased with cup size. Collapsed across cup sizes, students
      overpoured shots by 26%, mixed drinks by 80%, and beer by 25%. When a more
      liberal serving size of liquor (1.5 oz) was used as the standard, the results of
      the mixed drink task remained unchanged. However, the volumes poured by students
      during the shot free-pour task differed from the standard in only one cup size.
      CONCLUSIONS: The data suggest that college students drink more alcohol than
      indicated by their survey responses, raising questions about the validity of
      widely used alcohol surveys. Efforts to educate students about the alcohol
      content of standard drinks should be enhanced.

PMID- 14634491
TI  - I. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic
      liver disease: effects on drinking behavior by nurse/physician teams.
AB  - BACKGROUND: This multicenter prospective, randomized, double-blind placebo
      controlled trial was designed to evaluate the effectiveness of
      polyenylphosphatidylcholine against the progression of liver fibrosis toward
      cirrhosis in alcoholics. Seven hundred eighty-nine alcoholics with an average
      intake of 16 drinks per day were enrolled. To control excessive drinking,
      patients were referred to a standard 12-step-based alcoholism treatment program,
      but most patients refused to attend. Accordingly, study follow-up procedures
      incorporated the essential features of the brief-intervention approach. An
      overall substantial and sustained reduction in drinking was observed. Hepatic
      histological and other findings are described in a companion article. METHODS:
      Patients were randomized to receive daily three tablets of either
      polyenylphosphatidylcholine or placebo. Monthly follow-up visits included an
      extensive session with a medical nurse along with brief visits with a study
      physician (hepatologist or gastroenterologist). A detailed physical examination
      occurred every 6 months. In addition, telephone consultations with the nurse were
      readily available. All patients had a liver biopsy before entry; a repeat biopsy
      was scheduled at 24 and 48 months. RESULTS: There was a striking decrease in
      average daily alcohol intake to approximately 2.5 drinks per day. This was
      sustained over the course of the trial, lasting from 2 to 6 years. The effect was
      similar both in early dropouts and long-term patients, i.e., those with a 24
      month biopsy or beyond. CONCLUSIONS: In a treatment trial of alcoholic liver
      fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks
      was achieved with a brief-intervention approach, which consisted of a relative
      economy of therapeutic efforts that relied mainly on treatment sessions with a
      medical nurse accompanied by shorter reinforcing visits with a physician. This
      approach deserves generalization to address the heavy drinking problems commonly
      encountered in primary care and medical specialty practices.

PMID- 14634492
TI  - II. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in
      alcoholic liver disease.
AB  - BACKGROUND: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic
      cirrhosis in animals. Our aims were to determine the effectiveness of PPC in
      preventing or reversing liver fibrosis in heavy drinkers and to assess the extent
      of liver injury associated with the reduced drinking achieved in these patients.
      METHODS: This randomized, prospective, double-blind, placebo-controlled clinical
      trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97%
      male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of
      alcohol) for 19 years. A baseline liver biopsy confirmed the presence of
      perivenular or septal fibrosis or incomplete cirrhosis. They were randomly
      assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the
      main outcome measure was the stage of fibrosis compared with baseline.
      Progression was defined as advancing to a more severe stage. RESULTS: The 2-year
      biopsy was completed in 412 patients. PPC did not differ significantly from
      placebo in its effect on the main outcome. Alcohol intake was unexpectedly
      reduced in both groups to approximately 2.5 drinks per day. With this intake,
      21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo
      patients). The hepatitis C virus-positive subgroup exhibited accelerated
      progression. Improvement in transaminases and bilirubin favoring PPC was seen at
      some time points in other subgroups (hepatitis C virus-positive drinkers or heavy
      drinkers). CONCLUSIONS: PPC treatment for 2 years did not affect progression of
      liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin
      (in subgroups). One of five patients progressed even at moderate levels of
      drinking, and thus health benefits commonly associated with moderate drinking do
      not necessarily extend to individuals in the early stages of alcoholic liver
      disease.

PMID- 14634493
TI  - Ondansetron reduces mood disturbance among biologically predisposed, alcohol
      dependent individuals.
AB  - BACKGROUND: Early-onset alcoholics (EOA) differ from late-onset alcoholics (LOA)
      by developing problem drinking during youth, experiencing severe behavioral
      problems, having a familial disease history, and possessing a tendency toward
      subsyndromal mood disturbance, including symptoms of depression, anxiety, and
      hostility. Subsyndromal mood disturbance is, therefore, an important component of
      the early-onset syndrome and may be mediated by serotonin dysfunction. Therefore,
      the serotonin-3 antagonist ondansetron, which has been shown to be effective at
      improving drinking outcomes and promoting abstinence among EOA, presumably by
      ameliorating serotonin dysfunction, also may exert its beneficial effects by
      alleviating mood disturbance among EOA. METHODS: After one lead-in week of single
      blind placebo administration, subjects underwent 11 weeks of double-blind
      outpatient treatment using a 2 x 4 factorial design that examined age of onset
      (EOA versus LOA) and medication dose (placebo, or ondansetron 1, 4, or 16
      microg/kg twice daily) combined with weekly standardized group cognitive
      behavioral therapy. The placebo lead-in week was used to adjust for study
      entrance effects but not for excluding subjects. Assessments of mood were
      performed by using the overall score and subscales of the Profile of Mood States
      both at screening and at weekly intervals during the study. RESULTS: Subsyndromal
      mood disturbance was shown to be an important component of early-onset
      alcoholism. Ondansetron (16 microg/kg twice daily) showed greater therapeutic
      efficacy at alleviating symptoms of overall mood disturbance, fatigue, vigor,
      confusion/bewilderment, and depression among EOA compared with LOA. EOA
      associated improvements in mood disturbance seemed to be independent of drinking
      behavior. CONCLUSIONS: Ondansetron has been shown to be an effective treatment
      for early-onset alcoholism. Ondansetron's ability to improve symptoms of
      depression, anxiety, and hostility among EOA may make an additional contribution
      to its therapeutic effect. Mechanistic studies are needed to delineate more
      clearly the relationship between serotonin dysfunction and pathophysiology among
      various subtypes of alcohol-dependent individuals.

PMID- 14634494
TI  - Use of naltrexone in the treatment of alcoholism nationally in the Department of
      Veterans Affairs.
AB  - BACKGROUND: Naltrexone is one of only two medications currently approved by the
      Food and Drug Administration for the treatment of alcoholism. We attempted to
      determine the proportion of patients with a diagnosis of alcoholism who were
      prescribed naltrexone in the Department of Veterans Affairs health-care system
      during a 6-month period and the sociodemographic and clinical characteristics
      that distinguished them from veterans who were not prescribed naltrexone.
      METHODS: By using Veterans Affairs workload databases, all outpatients diagnosed
      with alcoholism (International Classification of Diseases, 9th revision, codes
      303.xx or 305.00) during a 6-month period (October 2000 to March 2001) were
      selected (n = 194,001). Patients in this group who were prescribed naltrexone
      during this period were identified. Logistic regression was used to compare those
      who were prescribed naltrexone with other alcoholics. RESULTS: In this sample,
      only 3,705 patients (1.9%) of the 194,001 veterans with an alcohol use disorder
      were prescribed naltrexone. Logistic regression analysis showed that naltrexone
      use was associated with comorbid disorders (bipolar disorder, dysthymia, major
      depressive disorder, posttraumatic stress disorder, and drug abuse) and recent
      psychiatric hospitalization. African Americans and veterans with organic brain
      syndromes were less likely to be prescribed naltrexone. CONCLUSIONS: These
      results suggest that prescribers have not embraced reports of naltrexone's
      efficacy in alcohol dependence, perhaps due to a general disinclination to use
      medications rather than a specific attitude toward naltrexone, especially in
      uncomplicated alcoholism.

PMID- 14634495
TI  - The prevalence of DSM-III-R alcohol dependence in two American Indian
      populations.
AB  - BACKGROUND: Evidence suggests that American Indian (AI) populations may be at
      increased risk for problems with alcohol, but a lack of community-based research
      using diagnostic criteria has constrained our ability to draw inferences about
      the extent of severe alcohol problems, such as dependence, in AI populations.
      METHODS: This article draws on data collected by the American Indian Service
      Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI
      SUPERPFP), which involved interviews with 3084 AI people living on or near their
      reservations. The AI-SUPERPFP sample was drawn from two culturally distinct
      tribes, which were designated with geographical descriptions: Northern Plains
      (NP) and Southwest (SW). Comparisons with data collected by the National
      Comorbidity Survey (NCS) were explored by using shared measures to situate the
      findings from AI-SUPERPFP in a national context. RESULTS: Lifetime rates of DSM
      III-R alcohol dependence for men in both AI-SUPERPFP samples were 50% higher than
      those found in the NCS. Rates of lifetime alcohol dependence for women varied by
      sample, however; NP women had twice the rate of women in the NCS, but SW women
      had rates quite similar to those of NCS women. Patterns for 12-month alcohol
      dependence in AI-SUPERPFP were generally more similar to those found in NCS.
      CONCLUSIONS: The rates of DSM-III-R alcohol dependence found in AI-SUPERPFP were
      generally higher than US averages and justify continued attention and concern to
      alcohol problems in AI communities, but they are not nearly as high as those in
      other reports in the literature that rely on less stringent sampling methods.
      Furthermore, significant sociocultural influences on the correlates of alcohol
      dependence in AI communities are evident in these data, underscoring the need to
      appreciate the complex and varying influences on the patterning of alcohol
      problems in the diverse cultural contexts of the US.

PMID- 14634496
TI  - Demographic characteristics of hospitalized patients with alcoholic liver disease
      and pancreatitis in los angeles county.
AB  - BACKGROUND: This study sought to identify demographic characteristics of
      hospitalized patients with alcoholic liver disease (ALD) in Los Angeles County
      for the purpose of implementing new preventive and educational programs. Another
      specific aim of the study was to characterize demographic and comorbid
      differences between patients with ALD and patients with pancreatitis, another
      alcohol-related disease. METHODS: Analyses were performed on discharge data from
      all nonfederal short-stay hospitals within Los Angeles County, released for the
      year 1999 by the Office of Statewide Health Planning and Development. Repeated
      hospital stays for ALD by the same patients were deleted from the data analysis
      based on individual identification numbers. For the analysis of medical costs of
      ALD, repeated hospital stays were included. RESULTS: Primary diagnosis of ALD
      accounted for 1.2% of total deaths among hospitalized patients and was the eighth
      most common cause of death among diseases examined. Moreover, the fatality rate
      of primary ALD among ALD hospital visits was the second highest, behind
      septicemia. ALD was most prevalent in the middle-aged (45-65 years old) and low-
      to middle-income men. The age-standardized hospitalization rate of ALD was
      highest in Hispanic men (61.1 per 100,000 per year), whereas that of chronic
      pancreatitis, another common complication of alcohol abuse, was most prevalent in
      African American men. CONCLUSIONS: Middle-aged Hispanic men with low- to middle
      income status were identified as a high-risk group for ALD in Los Angeles County.
      These data will guide us to develop a new strategy for future preventative and
      educational programs for ALD.

PMID- 14634497
TI  - The causal attribution of injury to alcohol consumption: a cross-national meta
      analysis from the emergency room collaborative alcohol analysis project.
AB  - BACKGROUND: Whereas a substantial literature exists documenting the association
      of alcohol and injuries, causal associations are less well established. METHODS:
      The relationship of drinking-in-the-event variables with attributing a causal
      association of alcohol consumption and the injury event was examined by using
      meta-analysis across 13 emergency room studies from 8 countries included in the
      Emergency Room Collaborative Alcohol Analysis Project. RESULTS: Pooled odds
      ratios for both log-transformed blood alcohol concentration at the time of the
      emergency room visit and the amount of alcohol consumed in the 6 hr before injury
      were positively predictive (1.19 and 1.80, respectively) and heterogeneous across
      studies. Effect size changed little when age and gender were controlled. When
      stratifying on reporting five or more drinks on an occasion during the last year
      (5+ yearly drinkers), the amount consumed was positively predictive of reporting
      a casual association of drinking and injury only for 5+ yearly drinkers. The
      effect size of feeling drunk at the time of injury, controlling for the amount of
      alcohol consumed, was positively predictive (2.04) but heterogeneous across
      studies. Meta-analysis regression found the level to which alcohol is consumed in
      a detrimental pattern to be a significant predictor of blood alcohol
      concentration, and of the amount consumed and feeling drunk at the time of
      injury, on causal attribution, with a lower detrimental pattern level with a
      larger effect size. CONCLUSIONS: The association of acute use of alcohol on
      causal attribution may be affected by chronic use to some extent, but this
      association is negatively affected by the degree to which a society exhibits
      harmful drinking patterns.

PMID- 14634498
TI  - Role of nitric oxide in alcohol alteration of beta-endorphin release from
      hypothalamic cells in primary cultures.
AB  - BACKGROUND: Nitric oxide (NO) mediates many pharmacological actions of ethanol.
      NO's role in regulating ethanol action on hypothalamic beta-endorphin (beta-EP)
      neurons is not established. METHODS: In this study, we determined the role of NO
      in ethanol regulation of beta-EP release from primary cultures of rat fetal
      mediobasal hypothalamic cells. Real-time polymerase chain reaction was used for
      messenger RNA (mRNA) detection; radioimmunoassay was used for hormone
      measurements. RESULTS: Acute ethanol treatment for 3 hr increased the release of
      beta-EP but reduced nitrite levels in the media of hypothalamic cells in primary
      cultures. In contrast, ethanol exposure for 48 hr reduced the release of beta-EP
      but increased the release of nitrite from these cells. Alcohol treatments altered
      the expression of neuronal NO synthase mRNA, but not inducible NO synthase mRNA,
      in a pattern similar to that of nitrite levels. Alcohol treatments blocked sodium
      nitroprusside-induced increases in the level of cellular cyclic guanidine
      monophosphate. The nonspecific NO blocker NG-nitro-l-arginine-methyl-esther, but
      not the inactive isomer N-nitro-d-arginine-methyl-esther (d-NAME), inhibited
      ethanol inhibitory actions on beta-EP release. CONCLUSIONS: These results suggest
      that the cyclic guanidine monophosphate/NO pathway is involved in ethanol
      alteration of hypothalamic beta-EP release.

PMID- 14634499
TI  - Leptin and cellular and innate immunity in abstinent alcoholics and controls.
AB  - BACKGROUND: Basic studies indicate that in vitro and in vivo doses of leptin
      modulate cellular immune responses. Given evidence that concentrations of leptin
      are altered in alcoholics who also show immune abnormalities, this study examined
      the relationships between circulating levels of leptin and markers of cellular
      and innate immunity. METHODS: Circulating levels of leptin, natural killer cell
      (NK) activity, interleukin-2 (IL-2)-stimulated NK activity, and concanavalin A
      stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between
      abstinent DSM-IV alcohol-dependent men (n = 27) and age- and gender-matched
      controls (n = 34). RESULTS: As compared with controls, alcoholics showed lower NK
      activity (p < 0.01) and a trend for lower levels of leptin (p = 0.055). In the
      total sample, leptin predicted NK activity (beta = 0.33; p < 0.05) after
      controlling for the confounding influence of body mass index, alcohol intake, and
      smoking. Leptin was not correlated with any of the cytokine measures. To examine
      whether the effects of leptin were mediated by its direct action on NK,
      additional studies examined in vitro effects of leptin on NK activity in healthy
      volunteers (n = 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK
      activity comparable to those with media alone. CONCLUSIONS: These data show that
      circulating levels of leptin are associated with NK activity in humans and
      suggest that abnormal in vivo concentrations of leptin may contribute to the
      declines of NK activity in alcoholics who are at risk for infectious diseases.

PMID- 14634500
TI  - Specific alteration of peripheral cytotoxic cell perforin expression in alcoholic
      patients: a possible role in alcohol-related diseases.
AB  - BACKGROUND: The association between chronic alcohol consumption and an increasing
      risk of infectious and neoplastic disease is related to an impairment of cellular
      immunity. However, studies of the number and activity of lymphocyte subsets show
      highly variable results. The aim of this study was to assess the expression of
      perforin, one of the main molecular agents of T and natural killer (NK) cell
      mediated cytotoxicity, in alcoholic patients without cirrhosis. METHODS: Eighteen
      patients with chronic alcoholism were prospectively included and compared with 18
      age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal
      hypertension, viral co-infection, other serious medical illness, and immune
      related medications were exclusion criteria. Lymphocyte phenotype was assessed,
      and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and
      NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and
      compared with that of 11 age- and sex-matched controls. RESULTS: The mean number
      of white blood cells and lymphocytes was not different between the controls and
      alcoholic patients, whereas the mean number of NK cells was significantly
      decreased in alcoholic patients (110 +/- 79/mm3 versus 271 +/- 192/mm3; p <
      0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly
      decreased in alcoholic patients compared with controls: 16 +/- 3% vs. 36 +/- 4%
      (p < 0.03) and 65 +/- 15% vs. 78 +/- 9% (p = 0.04), respectively. The percentage
      of cells expressing granzyme was similar in both groups. CONCLUSIONS: A decrease
      in perforin expression by cytotoxic cells could be a major factor in explaining
      the physiopathologic mechanisms of several alcohol-associated diseases.

PMID- 14634501
TI  - The effects of moderate ethanol consumption on the liver of the monkey, Macaca
      fascicularis.
AB  - BACKGROUND: Although evidence has accumulated for the cardioprotective effects of
      moderate ethanol consumption, little is known about the effects on the liver of
      consuming the equivalent of two drinks per day. The objective of this study was
      to determine the effects of moderate ethanol administration on the hepatic
      content of enzymes involved in ethanol oxidation, on hepatic lipid accumulation,
      and on serum markers of liver function/damage in the monkey, Macaca fascicularis.
      METHODS: Ovariectomized, adult monkeys were maintained for 34 months on an
      atherogenic diet containing cholesterol 1.21 mg/kJ. They were trained to drink
      ethanol plus vehicle at a dose of 0.5 g/kg body weight, which was administered 5
      days a week for 2 years. Blood was collected for ethanol concentrations (1 hr
      after ethanol administration) and was also assayed for gamma-glutamyltransferase,
      alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. Liver
      obtained at necropsy was analyzed for triglyceride and cholesterol contents and
      for alcohol dehydrogenase, cytochrome P450 2E1, and cytochrome P450 3A4 by
      Western blots. RESULTS: The blood ethanol concentrations measured 1 hr after
      ethanol administration were relatively constant over the 2-year dosing period.
      Hepatic levels of alcohol dehydrogenase and the cytochrome P450s were not
      significantly different between ethanol-consuming animals and control animals.
      Ethanol-associated increases in liver triglyceride were not significant due to
      high variability in hepatic lipid content in both the controls and ethanol
      consumers. However, covariance analyses using pretreatment concentrations of
      plasma cholesterol and apolipoprotein A-I suggested that the ethanol-related
      increase in hepatic free cholesterol was significant. Relative to controls,
      alcohol consumers had higher levels of serum ALT and a transient increase in ALP
      at 5 months. CONCLUSIONS: The observations made in this study on primates
      administered an atherogenic diet suggest that moderate ethanol ingestion has
      modest effects on the liver, including slightly increased ALT and ALP values.
      However, additional studies will be required to verify that this level of
      consumption is hepatotoxic when ingested over extended periods. This is still a
      concern because some human studies suggest that levels of ethanol considered to
      be cardioprotective cause liver injury when consumed over a lifetime.

PMID- 14634502
TI  - Alcohol-induced suppression of lung chemokine production and the host defense
      response to Streptococcus pneumoniae.
AB  - BACKGROUND: Acute alcohol intoxication impairs neutrophil migration in response
      to intrapulmonary infection with Streptococcus pneumoniae, the most common
      bacterial cause of pneumonia. Many of the same host defense functions that are
      impaired in the alcohol-intoxicated host are mechanistically associated with
      chemokines, a group of proinflammatory molecules that enhance neutrophil adhesion
      and direct neutrophil migration to sites of inflammation. The purpose of this
      study was to determine whether alcohol-induced chemokine suppression is
      responsible for impaired neutrophil recruitment into the lung during infection of
      the alcohol-intoxicated host. METHODS: S. pneumoniae was administered (107 colony
      forming units) intratracheally 30 min after intraperitoneal injection of 20%
      alcohol (5.5 g/kg) or saline. Four hours after bacterial challenge,
      bronchoalveolar lavage fluid (BALF) was collected, and the ability of BALF to
      induce neutrophil chemotaxis and adhesion molecule expression was measured by
      using chemotactic and flow cytometric assays. In another experiment,
      intratracheal challenge was performed by using recombinant macrophage
      inflammatory protein-2 (MIP-2), and BALF neutrophils were measured. RESULTS: BALF
      MIP-2 and cytokine-induced neutrophil chemoattractant were decreased by alcohol,
      and BALF from alcohol-intoxicated animals had decreased chemotactic activity for
      neutrophils, as well as a decreased ability to up-regulate neutrophil adhesion
      molecule expression, compared with controls. This decreased chemotactic activity
      was significantly increased in the alcohol group by repletion of chemokines to
      control levels. Alcohol also suppressed neutrophil recruitment after
      intrapulmonary challenge with MIP-2, suggesting that mechanisms other than
      chemokine suppression contribute to the alcohol-induced effect. CONCLUSIONS: At
      least two mechanisms, suppressed chemokine production and impaired neutrophil
      adhesion molecule expression, likely work in concert in the alcohol-intoxicated
      host to impair neutrophil adhesion and migration into the lung during
      pneumococcal infection. These alterations in neutrophil function likely increase
      the susceptibility of alcohol-consuming hosts to pneumonia.

PMID- 14634503
TI  - Chronic ethanol reduces nicotine-induced dopamine release in PC12 cells.
AB  - BACKGROUND: There is a high correlation between alcohol and nicotine use; that
      is, alcohol use is associated with high levels of smoking. One important aspect
      of nicotine addiction appears to be the activation of nicotinic acetylcholine
      receptors on dopaminergic neurons projecting from the ventral tegmental area to
      the nucleus accumbens. The release of dopamine from these neurons is thought to
      mediate, at least in part, the reward of nicotine consumption. If chronic alcohol
      consumption affects the amount of dopamine released in response to nicotine, it
      could contribute to the high level of smoking seen in alcoholics. METHODS: We
      have used an in vitro model system to study the effects of chronic ethanol
      exposure on acute nicotine-induced dopamine release and the withdrawal from
      ethanol. A pheochromocytoma cell line (PC12 cells) was exposed to ethanol for
      periods of 3 to 96 hr, followed by a 5 min exposure to nicotine. Dopamine
      released in response to nicotinic stimulation was measured by high-pressure
      liquid chromatography. RESULTS: Exposure of PC12 cells to chronic ethanol
      resulted in a time- and dose-dependent inhibition of nicotine-induced dopamine
      release. A moderate dose of ethanol (50 mM) resulted in a significant reduction
      in as little as 3 hr. The cells demonstrated a form of cross-tolerance in that
      they showed diminished response to nicotine even though they had never been
      exposed to nicotine. After ethanol was withdrawn from the cells after a chronic
      exposure (96 hr), dopamine release slowly returned to normal levels but
      demonstrated a significant period of "overshoot" or hyperresponsiveness between
      24 and 48 hr after withdrawal. CONCLUSIONS: These results show that chronic
      ethanol exposure decreases nicotine-induced dopamine release and demonstrate a
      period of hyperresponsiveness during withdrawal from ethanol. These studies
      suggest potential interactions between chronic ethanol and nicotine that may
      provide insight into such phenomena as cross-tolerance and increased use of
      nicotine by alcoholics.

PMID- 14634505
TI  - Current researches on breast cancer epidemiology in Korea.
AB  - As a cause of death in women, breast cancer ranks second to stomach cancer in
      Korea. Age-standardized mortality rates for breast cancer steadily increased
      during the 1980s and 1990s. There are big differences in the incidence rates for
      breast cancer compared with Western countries. Epidemiological features, trends
      in morbidity and mortality, various age-specific incidence curves, migrant study
      results, and analysis of the risk factors, however, suggest that the incidence of
      breast cancer might be further increasing in Korea. The key epidemiological
      hormonal risk factors for breast cancer are all explicable in terms of the
      estrogen augmented by progesterone hypothesis. These include older age, family
      history of breast cancer, early menarche, late menopause, late full-term
      pregnancy, and never a breast feeding. Both the establishment of high-risk groups
      and the estimation of lifetime risk are essential to develop a control strategy
      against breast cancer. Invasive ductal carcinoma is the most common histologic
      type of breast cancer in Korea, and the five-year survival rate has been
      estimated as 80-83%. Recent studies on the identification of susceptibility
      factors such as genetic polymorphisms of GSTM1/T1/P1, COMT, CYP2E1, CYP19, CYP17,
      ER-alpha, XRCC1, XRCC3, RAD52, TGF-alpha, TNF-alpha, IL-1B, IL-1RN, CDK7 etc.
      that predispose individuals to breast cancer by gene-environment or gene-gene
      interactions may possibly give further insight into both the etiology and the
      prevention of this malignancy.

PMID- 14634506
TI  - Evolving entities and changing concepts in breast pathology.
AB  - Among the evolving entities and changing concepts in breast pathology are those
      relating to columnar cell hyperplasia, pseudoangiomatous stromal hyperplasia,
      mucocele-like lesions, pleomorphic lobular carcinoma in situ, pseudo-Paget's
      disease of nipple, microinvasive carcinoma of breast, spindle cell metaplastic
      carcinoma, and minimal metastatic disease in axillary lymph nodes. Pathologists,
      as well as physicians involved in the management of breast diseases, need to be
      aware of these recent developments in breast pathology since the recognition and
      understanding thereof may have considerable clinical relevance.

PMID- 14634507
TI  - Upregulation and overexpression of human X-box binding protein 1 (hXBP-1) gene in
      primary breast cancers.
AB  - BACKGROUND: Human X-box binding protein 1 (hXBP-1) is a transcription factor
      essential for hepatocyte growth as well as for plasma cell differentiation. hXBP
      1 also binds to cis-elements of human T cell leukemia virus and human major
      histocompatibility complex genes. In order to clarify the role of XBP-1 in breast
      cancer, here we investigated the expression of XBP-1 in 11 primary breast cancers
      and 5 breast cancer cell lines. MATERIALS AND METHODS: The study population
      consisted of eleven patients who were underwent surgery for breast cancer from
      2000 to 2002. Five breast cancer cell lines (MDA-MB-453, CRL1500, YMB-1-E, MCF7
      and HBL100) were analyzed for XBP-1 expression. Reverse transcription polymerase
      chain reaction was performed on 6 primary breast cancers. Then we investigated
      XBP-1 expression by immunohistochemically on archived paraffin-embedded sections.
      RESULTS: hXBP-1 mRNA expression was increased in all 11 primary breast cancers we
      examined, as well as 5 breast cancer cell lines, but hardly detectable in non
      cancerous breast tissue. Immunohistochemical staining demonstrated that hXBP-1
      protein stained strongly in the cytoplasm of cancer cells but was unreactive in
      the normal breast ductal epithelial and myoepithelial cells. CONCLUSIONS: These
      data indicate that increased expression of the hXBP-1 gene may play some role in
      human breast carcinogenesis through impairment of cell differentiation
      regulation.

PMID- 14634508
TI  - Association of p53 codon Arg72Pro and p73 G4C14-to-A4T14 at exon 2 genetic
      polymorphisms with the risk of Japanese breast cancer.
AB  - BACKGROUND: The association between breast cancer risk and genetic polymorphisms
      of p53 at codon 72 (Arg72Pro) has been investigated by several studies, but the
      results are not consistent. The aim of this case-control study conducted in
      Nagoya, Japan, was to reconfirm the results of prior studies of polymorphisms of
      p53 Arg72Pro, and to test if polymorphisms of p73 G4C14-to-A4T14 at exon 2 (G4A)
      were also associated with breast cancer risk. METHODS: The cases were 200 breast
      cancer patients who visited Aichi Cancer Center Hospital. The controls were 282
      local citizens who underwent a health check-up. All cases and controls were
      recruited from Chubu Japan. Genotyping was carried out by polymerase chain
      reaction with confronting two-pair primers. RESULTS: The p53 genotype
      distribution was 40.4% for Arg72 homozygous, 48.9% for heterozygous, and 10.7%
      for Pro72 homozygous in controls, and 32.0%, 50.0%, and 18.0% in cases,
      respectively. A comparison between cases and controls indicated a significantly
      increased risk for Pro72 homozygosity in cases (odds ratio=2.14; 95% confidence
      interval=1.21-3.79). The genotypic frequencies for p73 G4A were 54.3% for G/G,
      39.7% for G/A, and 6.0% for A/A in controls; and 59.0%, 32.0%, and 9.0% in cases,
      respectively. There were no significant differences in p73 G4A frequency between
      cases and controls. CONCLUSIONS: This study implies an association of breast
      cancer risk with the p53 polymorphism Arg72Pro, but not with p73 G4A.

PMID- 14634509
TI  - Prognostic value of microvessel density in invasive ductal carcinoma of the
      breast.
AB  - BACKGROUND: Although the prognostic value of microvessel density (MVD) has been
      studied in breast cancer, the results still remain controversial. PATIENTS AND
      METHODS: Paraffin embedded sections of invasive ductal carcinoma of the breast
      were immunohistochemically stained for factor VIII- related antigen in 252
      patients with a median follow-up duration of 7.0 years. MVD quantification of the
      three most vascular areas at a magnification of x 200 was performed. RESULTS: The
      252 patients were stratified into high and low MVD groups according to a cut-off
      value that was the upper one-third MVD value of all patients. The patients with a
      high MVD had a significantly worse outcome in terms of both disease free survival
      (DFS) (p< 0.0001) and overall survival (OS) (p= 0.0012) compared with those with
      a low MVD. The same effects were seen in patients with lymph node negative as
      well as positive breast cancer. Multivariate analyses indicated the nodal status,
      nuclear grade and MVD (p= 0.0001) to be independent prognostic factors for the
      DFS, while the nodal status, estrogen receptor status, tumor size and MVD (p=
      0.0006) were independent prognostic factors for the OS. CONCLUSION: MVD was found
      to be an independent prognostic indicator of recurrence and death for breast
      cancer, and is therefore considered to be a useful factor for selecting high risk
      patients to receive adjuvant therapies.

PMID- 14634510
TI  - A comparison of MR imaging, galactography and ultrasonography in patients with
      nipple discharge.
AB  - BACKGROUND: The aim of this study is to assess the usefulness of three
      dimensional contrast-enhanced magnetic resonance (MR) imaging, compared with
      galactography and ultrasonography(US). METHODS: Fifty-five patients with bloody
      nipple discharge were investigated retrospectively. All patients were examined by
      galactography, ultrasonography and MR imaging. These three sets of findings were
      compared with the histopathological results from 16 intraductal biopsies, 3
      excisional biopsies, 24 microdochectomies and 12 mastectomies. RESULTS: Contrast
      enhanced MR imaging demonstrated all malignant lesions including ductal carcinoma
      in situ (DCIS). Four cases of DCIS were not visualized by ultrasonography and
      three malignant lesions were missed by galactography. In the MR study, segmental
      clumped enhancement (positive predictive value =100 %), and focal mass with
      smooth border (negative predictive value =87.5 %) were the statistically
      significant predictive factors. CONCLUSIONS: Among the three modalities, contrast
      enhanced three-dimensional MR imaging demonstrated the location and distribution
      of the lesions most clearly, especially in cases of ductal carcinoma in situ. It
      has the potential to be a useful diagnostic tool for patients with nipple
      discharge.

PMID- 14634511
TI  - Occult breast carcinoma presenting with axillary lymph node metastases: follow-up
      of eleven patients.
AB  - BACKGROUND: Breast carcinoma presenting with axillary metastases and no
      clinically apparent primary tumor in the breast is an uncommon form of stage
      IIdisease. The methods of diagnosis and treatment of these patients are not
      established. We present our eleven treated cases of occult carcinoma and discuss
      the issues of evaluation and management. METHODS: Eleven patients with occult
      breast carcinoma (OBC) presenting between January, 1985 and April, 1998 at the
      National Shikoku Cancer Center were evaluated clinically and with
      immunohistochemical staining. Immunohistochemical staining was performed using
      the Envision method. The primary antibodies for gross cystic disease fluid
      protein-15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) were
      used. RESULTS: Nine patients underwent mastectomy. Breast-conserving surgery was
      performed in one patient. One patient did not receive any operation for the
      breast. No primary tumor was found among three of nine cases receiving
      mastectomy. Some adjuvant therapies after the operation were performed in eight
      cases. Follow-up ranged from 5 to 310 months (median, 54 months), and the five
      year disease free survival rate was 62.5%. There were eight GCDFP-15 positive
      cases (72.7%) and four ER and/or PR positive cases (36.4%). CONCLUSIONS: GCDFP-15
      is useful for confirming the primary site of breast carcinoma. Ultrasonography,
      computed tomography, and magnetic resonance imaging are thought to be good for
      detecting occult primary tumors. The incidence of OBC is still unclear, but it is
      possible that these patients need to be treated as typical stage II patients.

PMID- 14634512
TI  - Detection of bone metastases in routine follow-up after treatment for primary
      breast cancer.
AB  - BACKGROUND AND OBJECTIVES: The effect of follow-up after primary treatment for
      breast cancer on overall survival remains highly questionable, and controversy
      still exists regarding the benefits of regular follow-up. We therefore attempted
      to assess the role of intensive follow-up in patients with bone metastases.
      METHODS: We analyzed the survival of 87 breast cancer patients who relapsed first
      in bone diagnosed either with or without symptoms, from 1985 to 1998. Overall
      survival (OS) was the main outcome. Recurrence was coded as either asymptomatic,
      elevated tumor marker, or symptomatic. RESULTS: The median disease free interval
      was 33 months in the asymptomatic group, 42 months in the elevated tumor marker
      group, and 43 months in the symptomatic group. Overall survival did not differ
      significantly between the groups. The median OS was 77 months in the asymptomatic
      group, 78 months in the elevated tumor marker group, and 79 months in the
      symptomatic group. CONCLUSIONS: Our study showed that intensive testing,
      including assessment of serum tumor markers and bone scans, did not improve OS.
      The results of our study supported the American Society of Clinical Oncology
      (ASCO) recommendations that routine use of bone scans is not recommended.

PMID- 14634513
TI  - Outcome of breast-conserving therapy in the Tokyo Women's Medical University
      Breast Cancer Society experience.
AB  - BACKGROUND: The results of BCT in Japanese women have not been fully evaluated.
      The Tokyo Women's Medical University Breast Cancer Society initiated BCT
      protocols in 1987. Here, we present a retrospective analysis of BCT outcomes and
      identify prognostic factors. METHODS: The study population comprised 348 patients
      (353 breasts) with UICC clinical stage 0,I or II breast cancer, for whom wide
      excision (n= 294), quadrantectomy (n= 56) and tumorectomy (n= 3) were performed.
      The final pathological margin states were positive in 102 breasts (cancer cells
      remained within 5 mm of the surgical margin). The whole breast was irradiated to
      a total dose with 44 Gy/20 fractions or 46 Gy/23 fractions in the patients with
      negative surgical margins. The patients with positive or close margins received
      48.4 Gy/22 fractions or 50 Gy/25 fractions irradiation to the whole breast. All
      but 2 patients received a radiation boost to the tumor bed and all tumor beds
      were irradiated to more than 53 Gy. Adjuvant therapy was administered in 240
      cases. The median follow-up time was 4.3 years. RESULTS: The 5-year overall,
      cause-specific and disease-free survival rates were 95.8%, 97.3% and 92.5%,
      respectively. Recurrence was observed in 29 patients including 11 patients with
      loco-regional recurrence. Local recurrence was observed in 6 patients, 5 of whom
      were premenopausal. The 5-year local control and loco-regional control rates were
      98.9% and 96.6%, respectively. T status (T1 to T2) was the only significant
      prognostic factor for disease-free survival. No severe morbidity has been
      observed. Cosmetic results were excellent or good in 73% of patients. CONCLUSION:
      Our BCT protocols provide a high rate of local control and good cosmetic outcome.
      Pathologic margin status was not a major prognostic factor for local recurrence.
      Long term follow-up is required to reach a definite conclusion on optimal BCT
      protocols.

PMID- 14634514
TI  - Radiation therapy for brain metastases from breast cancer.
AB  - BACKGROUND: Breast cancer is one of the most common malignancies that metastasize
      to the brain. Radiation therapy plays a central role in the management of brain
      metastases. METHODS: The medical records of 36 patients with brain metastases
      from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto
      University Hospital between 1993 and 2001 were reviewed. The treatment outcomes
      were analyzed retrospectively. RESULTS: The median age at the time of diagnosis
      of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis,
      while the others had multiple metastases. Uncontrolled extracranial metastases
      were present in 26 patients at the time of diagnosis of brain metastases. All
      patients received WBRT at a median dose of 31 Gy. Eight patients received
      conventional external-beam boost irradiation, and 2 received boost stereotactic
      radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled
      extracranial metastases except for bone metastases and old age were significantly
      associated with a poor survival rate. Twenty-six patients (82%) showed initial
      response, but 15 developed CNS failure, including 9 patients whose tumor recurred
      at the original site, 4 patients who developed tumors elsewhere in the brain and
      3 patients who exhibited meningeal spread. The median duration of intracranial
      failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect
      intracranial control. CONCLUSIONS: Radiation therapy yielded a high initial
      response, but the duration of effect was limited with external beam irradiation
      alone. New treatment strategies such as adding SRS need to be studied further.

PMID- 14634515
TI  - Invasive micropapillary carcinoma of the breast with minimal regional lymph node
      metastasis regardless of the huge size: report of a case.
AB  - We present a 38-year-old premenopausal Japanese woman with invasive
      micropapillary carcinoma (IMC) of the left breast with minimal lymph node
      metastasis despite a huge size. The patient noticed a left breast mass and a
      bloody nipple discharge 2 years before admission. On admission, physical
      examination revealed a huge, elastic hard mass with skin ulcer 12x12 cm in
      diameter occupying the entire left breast. The patient underwent modified radical
      mastectomy with level III lymph node dissection, and the defect was reconstructed
      with a vertical rectus abdominis myocutaneous flap. Histopathologically, IMC
      comprised about 60% of the tumor, admixed with papillotubular and mucinous
      carcinoma. Only one of twenty-five lymph nodes had tumor metastasis. The patient
      remains well 8 months postoperatively without any signs of recurrence.

PMID- 14634516
TI  - Long-term suppression of lymphangitic lung metastasis from breast cancer using
      biweekly docetaxel: a case report.
AB  - A 45-year-old woman underwent a modified radical mastectomy for right breast
      cancer in July 1996. As lymph node metastases were quite advanced, chemotherapy
      was started with anthracyclines. Four years after surgery, cough and dyspnea
      appeared. Chest radiograph and CT showed reticular shadows bilaterally and slight
      pleural effusion, suggesting lymphangitic lung metastasis of breast cancer.
      Biweekly intravenous docetaxel (TXT,45 mg/m2) was initiated. Four courses of TXT
      ameliorated her complaints and radiographic findings. A total of 30 continuous
      courses of TXT suppressed disease exacerbation for 18 months until new lesions
      manifested in January 2002. The main side effects were grade 2 leukopenia and
      alopecia. This case report describes a patient with long-term suppression of
      lymphangitic lung metastasis of breast cancer using biweekly TXT without severe
      side effects or worsening quality of life.

PMID- 14634517
TI  - A case of chest wall recurrence of breast cancer treated with paclitaxel weekly,
      5'-deoxy-5-fluorouridine, arterial embolization and chest wall resection.
AB  - Chest wall resection and reconstruction has proved to be a safe surgical
      procedure for local recurrence of breast cancer. Recently, as second- or third
      line chemotherapy for the patients with recurrent breast cancer or ovarian
      cancer, weekly paclitaxel has provided a significant response rate in those
      patients, and generated much clinical interest. We report here a case of chest
      wall recurrence of breast cancer successfully treated by a combination of weekly
      paclitaxel, 5'-deoxy-5-fluorouridine, arterial embolization, and chest wall
      resection. A 56-year-old woman presented with a large mass in the left anterior
      chest. A recurrent tumor developed and enlarged one-and-half years after
      undergoing modified radical mastectomy for advanced breast cancer (T4N2M0, stage
      III B) at another hospital. The mass had enlarged while the patient underwent
      chemotherapy with cyclophosphamide, doxorubicin, 5-fluorouracil, and anastozole,
      followed by low-dose cisplatin, 5-fluorouracil, and goserelin. To reduce the mass
      and inflammatory changes of the skin, weekly paclitaxel and 5'-deoxy-5
      fluorouridine was given. Furthermore, to obtain hemostasis and promote the mass
      reduction, arterial embolization of the supply arteries was performed. Chest wall
      resection, reconstruction of the bony chest wall with polypropylene mesh folded 8
      times, and soft tissue reconstruction with a contralateral myocutaneous flap were
      carried out successfully. The patient was discharged from the hospital ten weeks
      after the operation without any major morbidity, and remained well for ten
      months. A multimodal approach with chemotherapy and arterial embolization was
      effective in this case in treating chest wall recurrence of breast cancer.
      Reconstruction of the chest wall bone with polypropylene mesh folded 8 times and
      soft tissue reconstruction with a contralateral myocutaneous flap was a useful
      procedure after chest wall resection, even after chemotherapy and arterial
      embolization.

PMID- 14634518
TI  - A case of diabetic mastopathy with multiple lesions mimicking breast cancer.
AB  - We report a case of diabetic mastopathy with multiple unilateral lesions in an
      insulin dependent patient. The patient was a 62-year-old woman with two hard
      tumors in the right breast, who had been treated with insulin for diabetes
      mellitus. Mammography revealed a highly dense tumor in the right breast, while
      ultrasonography showed two irregular hypoechoic lesions with marked posterior
      acoustical shadowing, suggesting scirrhous carcinoma. On magnetic resonance
      imaging the two lesions had slightly heterogeneous enhancement. Aspiration breast
      cytology showed insufficient cellular material for evaluation. Excisional biopsy
      was performed because the patient wanted confirmation and treatment. Fibrosis
      with dense lymphocytic infiltration around the lobules and ducts was diagnosed
      histopathologically. These findings were compatible with diabetic fibrous
      mastopathy. Although this disease is thought to be a diabetes-induced reaction of
      autoimmune origin, multiple lesions are rare. This is the first case of
      unilateral multiple lesions of diabetic mastopathy.

PMID- 14634519
TI  - Diabetic mastopathy in an advanced elderly woman with insulin-dependent type 2
      diabetes mellitus.
AB  - Diabetic mastopathy is an unusual stromal fibrotic lesion, but typically occurs
      in long-standing insulin dependent and younger diabetic patients. We report a
      case of diabetic mastopathy in an older diabetic patient. The patient was a 76
      year-old woman with a history of type 2 diabetes mellitus for 13 years and 3
      years of insulin treatment. She developed a 3 cm, hard, mobile nodule in the left
      breast. Mammography revealed a dense mass. Ultrasonography showed an irregular
      shaped hypoechoic lesion with an unclear boundary and acoustic shadowing. Since
      fine needle aspiration biopsy delivered insufficient material and core needle
      biopsy did not yield any specific findings for diagnosis, clinically diabetic
      mastopathy was the prime suspect but breast cancer could be completely ruled out.
      Surgical excision was thus performed and diabetic mastopathy was confirmed
      pathologically. We report on this rare case of diabetic mastopathy in a 76 year
      old type 2 diabetic patient.

PMID- 14634520
TI  - Granulomatous mastitis diagnosed by core-needle biopsy and successfully treated
      with corticosteroid therapy: a case report.
AB  - A 46-year-old woman presented to our hospital with a rapidly growing lump in her
      right breast. Fine-needle aspiration (FNA) cytology and core needle biopsy of the
      mass revealed many epithelioid cells admixed with multinucleated Langhans-type
      giant cells, neutrophils, lymphocytes, and stromal cells, leading to a diagnosis
      of granulomatous mastitis. Mammography and ultrasonography provided little
      information for differentiating between granulomatous mastitis and carcinoma.
      This patient was successfully treated with low dose and short period of
      corticosteroid therapy.

PMID- 14634543
TI  - The effects of transdermal estrogen therapy on bone mass and turnover in early
      postmenopausal smokers: a prospective, controlled study.
AB  - OBJECTIVE: The purpose of this study was to investigate whether smoking reduces
      the effects of transdermal estrogen replacement therapy on bone. STUDY DESIGN:
      One hundred forty-eight women (0.5-5 years after menopause, aged 46-58 years)
      completed the study. Smokers were assigned randomly to receive either 1.0 mg
      (n=32 women) or 1.5 mg (n=31 women) of transdermal estradiol in gel daily, and
      nonsmokers (n=46 women) were assigned to receive 1.0 mg of transdermal estradiol
      for 2 years. The control group consisted of 17 smokers and 22 nonsmokers. Bone
      mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover
      was assessed by measurements of urinary aminoterminal telopeptide of type I
      collagen and serum aminoterminal propeptide of type I procollagen. RESULTS:
      Lumbar spine bone mineral density increased similarly in smoking (+3.6%) and
      nonsmoking (+2.6%) estrogen users (P<.0001 to a decrease of 2.5% in the control
      group). Femoral neck bone mineral density increased 2.2% to 2.4% in smoking and
      nonsmoking estrogen users but decreased 0.2% in control subjects (P<.05). Urinary
      aminoterminal telopeptide of type I collagen decreased similarly in all estrogen
      using groups (P<.05 to control group), but serum aminoterminal propeptide of type
      I procollagen decreased more in smoking than in nonsmoking estrogen users
      (P=.006). Serum 25-hydroxyvitamin D was 20% lower (P=.004) in smokers than in
      nonsmokers. CONCLUSION: Transdermal estrogen treatment protects smoking women as
      effectively as nonsmokers from osteoporosis. Smoking worsens the vitamin D state
      of postmenopausal women.

PMID- 14634544
TI  - Effects of low-dose oral and transdermal estrogen replacement therapy on
      hemostatic factors in healthy postmenopausal women: a randomized placebo
      controlled study.
AB  - OBJECTIVE: This study was undertaken to investigate the effect of transdermal and
      oral estrogen replacement therapy in healthy postmenopausal women on markers of
      coagulation and fibrinolysis associated with coronary artery disease. STUDY
      DESIGN: In a randomized, placebo-controlled, double-blind study, healthy
      hysterectomized postmenopausal women received daily either placebo (n=49),
      transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg
      (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G
      group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were
      measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS:
      No significant changes versus baseline and placebo were found in the tE(2) group,
      except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%,
      P=.01). In the oE(2) group, significant percentage changes from baseline versus
      placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3%
      (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type
      plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the
      oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5%
      (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant
      changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)
      antiplasmin complexes. CONCLUSION: Low-dose oral estradiol therapy was associated
      with an increase in fibrinolysis and small decreases in procoagulant variables.
      Transdermal therapy had minor effects.

PMID- 14634545
TI  - Decision analysis of hormone replacement therapy after the Women's Health
      Initiative.
AB  - OBJECTIVES: The purpose of this study was to estimate the quality-adjusted life
      expectancy with and without hormone replacement therapy. STUDY DESIGN: We
      compared the quality-adjusted life expectancy with and without combination
      hormone replacement therapy in three cohorts of women with menopausal symptoms
      over a 20-year period using a Markov decision-analysis model. Women were either
      at high or low risk for breast cancer and coronary heart disease or at high risk
      for osteoporosis. RESULTS: Hormone replacement therapy decreases life expectancy
      slightly compared with no hormone replacement therapy if menopausal symptoms are
      not considered. However, if relief from menopausal symptoms is considered and the
      usefulness of life with symptoms is worth <0.996 compared with life without
      symptoms, then 5 years of hormone replacement therapy provides equivalent quality
      adjusted life-years. CONCLUSION: Combination hormone replacement therapy
      decreases life expectancy if quality of life with menopausal symptoms is not
      considered. However, the benefit of hormone replacement therapy can exceed the
      risk for women with menopausal symptoms.

PMID- 14634546
TI  - Association between vitamin D receptor gene haplotypes and bone mass in
      postmenopausal Korean women.
AB  - OBJECTIVES: The objective of the study was to evaluate the effect of vitamin D
      receptor (VDR) gene haplotypes on bone mineral density (BMD). STUDY DESIGN: The
      VDR Bsm I, Apa I, Taq I, and poly(A) polymorphisms were analyzed in 417
      postmenopausal Korean women. Serum 1,25(OH)(2) vitamin D(3), osteocalcin, bone
      alkaline phosphatase, and CrossLaps were measured by immunoradiometric assay and
      enzyme-linked immunosorbent assay. BMD at the lumbar spine and proximal femur was
      determined by dual-energy x-ray absorptiometry. RESULTS: At all skeletal sites,
      genotypes not carrying the baTL haplotype allele (uppercase letters signifying
      the absence, lowercase letters the presence, of the restriction site, and L a
      repeat length of more than 17) had significantly lower BMD than baTL homozygotes.
      The former genotypes were more prevalent in women with low bone mass than in
      healthy women. No significant differences in vitamin D(3) or bone markers levels
      were noted among the baTL haplotype genotypes. CONCLUSION: The VDR baTL haplotype
      allele is related to bone mass in Korean women.

PMID- 14634547
TI  - Colpocleisis and urinary incontinence.
AB  - OBJECTIVE: The study was undertaken to review results of colpocleisis performed
      for advanced pelvic organ prolapse (POP) in elderly women, with attention to
      perioperative stress incontinence. STUDY DESIGN: We performed a retrospective
      chart review of all colpocleisis procedures performed July 2000 through March
      2002. RESULTS: Sixty-four women with median age 78 years (68-90 years) with
      symptoms and signs of advanced POP underwent partial vaginectomy and
      colpocleisis. Concomitantly, 21 (33%) women underwent suburethral sling and 12
      (19%) underwent suburethral plication procedures for treatment of stress urinary
      incontinence (SUI). Three patients with dementia were unable to offer subjective
      symptoms. One patient died in hospital from multisystem organ failure unrelated
      to colpocleisis. When last seen, 2 (3%) of the remaining 60 patients had some
      persistence of symptoms of POP. Of 30 women without preoperative symptoms of SUI,
      8 had new-onset SUI symptoms after surgery. CONCLUSION: Colpocleisis is an
      effective method for treatment of advanced POP. Lower urinary tract evaluation
      and treatment remain challenging in this setting.

PMID- 14634548
TI  - Abdominal sacrohysteropexy in young women with uterovaginal prolapse: long-term
      follow-up.
AB  - OBJECTIVE: The purpose of this study was to evaluate the long-term efficiency
      after abdominal sacrohysteropexy in women with uterovaginal prolapse. STUDY
      DESIGN: We conducted a retrospective chart review at our tertiary referral
      urogynecology unit. Thirty women of childbearing age with uterovaginal prolapse
      who wanted uterine preservation underwent abdominal sacrohysteropexy between 1987
      and 1999. RESULTS: The mean age of the women was 35.7 years (range, 29-43 years).
      All women were parous. Thirteen women had grade 2 uterovaginal prolapse, and 17
      women had grade 3 prolapse. In all women, the Burch procedure and posterior
      colporrhaphy were performed at the same time. Intraoperative and postoperative
      complications occurred in 2 patients (6.6%) and 4 patients (13.3%), respectively.
      The mean objective and subjective follow-up periods were 44.5 months (range, 2
      156 months) and 94.6 months (range, 8-160 months), respectively. At the time of
      the last physical examination, there were two cases of recurrent uterovaginal
      prolapse (6.6%), which was symptomatic in 1 patient and required repeat surgical
      treatment. At the time of the last questionnaire, apart from the patient who
      underwent repeat surgery, no patients had any uterovaginal prolapse symptoms.
      Three women had pregnancies that were conceived spontaneously, which led to three
      early legal abortions. CONCLUSION: The abdominal sacrohysteropexy is effective
      and safe in the treatment of uterovaginal prolapse in women of childbearing age.
      This procedure has a high success rate in correcting prolapse without a time
      dependent decrease in efficiency.

PMID- 14634549
TI  - Elective cesarean delivery for women with a previous anal sphincter rupture.
AB  - OBJECTIVE: The purpose of this study was to evaluate elective cesarean delivery
      for women with a history of anal sphincter rupture. STUDY DESIGN: The
      effectiveness of cesarean delivery in parous women with a previous anal sphincter
      rupture was determined by decision analysis. The outcomes were excess cesarean
      deliveries and morbidity and mortality rates per prevented case of anal
      incontinence. RESULTS: We needed 2.3 cesarean deliveries to prevent one case of
      anal incontinence. A woman who chooses a cesarean delivery has a 11.3% risk of
      morbidity compared with a 4.2% risk for vaginal delivery (relative risk, 2.7; 95%
      CI, 2.6-2.8; P<.001). The relative risk for maternal death from a cesarean
      delivery is 2.6 (95% CI, 1.5-4.5; P<.001). CONCLUSION: Continent women with a
      previous anal sphincter rupture who are delivered vaginally are at high risk for
      permanent anal incontinence. Cesarean delivery will prevent most cases of anal
      incontinence, although marginally increasing maternal risk. The increased risk
      may be justified by the potential benefits. Patients should be counseled on these
      risks and benefits.

PMID- 14634550
TI  - Objective structured assessment of technical skills for episiotomy repair.
AB  - OBJECTIVE: This study was undertaken to estimate the reliability and validity of
      an objective structured assessment of technical skills (OSATS) for midline
      episiotomy repair using a lifelike anatomic model. STUDY DESIGN: Eighteen
      residents were administered an episiotomy OSATS. Two evaluators independently
      completed an objective score sheet assessing six key components of the repair,
      seven global surgical skills, and a pass/fail score for each resident. Residents
      also completed an anonymous self-assessment. RESULTS: Reliability indices were
      0.95 for the checklist and global surgical skills rating. Construct validity
      found significant differences on the checklist, global surgical skills, and
      pass/fail score sheets by residency level. Residents more often assessed their
      own global surgical skills performance lower than the independent evaluators.
      Surprisingly, 61% (11/18) of the residents failed the assessment, including all
      postgraduate year 1 and postgraduate year 2 residents. CONCLUSION: Episiotomy
      OSATS that used task-specific and global checklists provide a reliable and valid
      method of assessing resident skills in this anatomic model, and performance
      correlates with resident year level of training.

PMID- 14634551
TI  - Epidemiologic evaluation of reoperation for surgically treated pelvic organ
      prolapse and urinary incontinence.
AB  - OBJECTIVE: The purpose of this study was to measure the risk of reoperation for
      surgically treated pelvic organ prolapse and urinary incontinence in a community
      based population. STUDY DESIGN: A 5-year prospective, observational study was
      conducted of women who had undergone pelvic organ prolapse and urinary
      incontinence surgery in 1995. The cohort of 376 women was identified by
      International Classification of Diseases, 9th revision, and current procedural
      terminology codes in 149,554 reproductive-aged women within the Kaiser Permanente
      Northwest membership. RESULTS: Thirty-six women underwent 40 cases of
      reoperation. By survival analysis, 13% of women underwent reoperation by 71
      months. Having undergone previous pelvic organ prolapse and urinary incontinence
      surgery increased the risk of reoperation to 17% compared with 12% for women who
      underwent a first procedure (log rank, P=.04). No association was observed with
      age, body mass index, parity, previous hysterectomy not for prolapse, vaginal
      versus abdominal approach, severity of prolapse, ethnicity, chronic lung disease,
      smoking, previous corticosteroid use, and estrogen status. CONCLUSIONS: Future
      reoperation is a significant risk of morbidity for women who undergo pelvic organ
      prolapse and urinary incontinence surgery.

PMID- 14634552
TI  - Vaginal delivery parameters and urinary incontinence: the Norwegian EPINCONT
      study.
AB  - OBJECTIVE: The study was undertaken to investigate the effect of nine delivery
      parameters on urinary incontinence in later life. STUDY DESIGN: Incontinence data
      from the EPINCONT study were linked to the Medical Birth Registry of Norway.
      Effects of birth weight, gestational age, head circumference, breech delivery,
      injuries in the delivery channel, functional delivery disorders, forceps
      delivery, vacuum delivery, and epidural anesthesia were investigated. The study
      covered women younger than 65 years, who had had vaginal deliveries only
      (n=11,397). RESULTS: Statistically significant associations were observed between
      any incontinence and birth weight 4000 g or greater (odds ratio [OR] 1.1, 95% CI
      1.0-1.2); moderate or severe incontinence and functional delivery disorders (OR
      1.3, 95% CI 1.1-1.6); stress incontinence and high birth weight (OR 1.2, 95% CI
      1.1-1.3) and epidural anesthesia (OR 1.2, 95% CI 1.0-1.5); and urge incontinence
      and head circumference 38 cm or larger (OR 1.8, 95% CI 1.0-3.3). CONCLUSION: The
      effects were too weak to explain a substantial part of the association between
      vaginal delivery and urinary incontinence, and statistically significant results
      may have incurred by chance.

PMID- 14634553
TI  - Burden of stress urinary incontinence for community-dwelling women.
AB  - OBJECTIVE: The purpose of this study was to better understand the subjective
      bothersomeness of stress urinary incontinence symptoms and their impact on the
      quality of life of community-dwelling women. STUDY DESIGN: We conducted a mail
      survey of 605 women in the United States who reported symptoms of stress urinary
      incontinence. RESULTS: More than three fourths of the respondents reported their
      symptoms to be bothersome, with approximately 29% reporting their symptoms to be
      moderately to extremely bothersome. The odds of moderate-to-extreme bother
      decreased with age and increased with symptom severity. Concerns about social
      embarrassment were evident. CONCLUSION: Stress urinary incontinence symptoms can
      impose a significant burden on the women who have them. The results reinforce the
      need for health care professionals to be proactive in questioning and educating
      patients about this common lower urinary tract symptom.

PMID- 14634554
TI  - Does ovarian blood flow distinguish between ovulatory and anovulatory patients
      with polycystic ovary syndrome?
AB  - OBJECTIVE: The purpose of this study was to determine whether parameters of
      ovarian blood flow distinguish between women with polycystic ovary syndrome
      (PCOS) who ovulate and those who are anovulatory. STUDY DESIGN: This was a
      prospectively enrolled trial, carried out as a cross-sectional comparison of 12
      ovulatory patients with PCOS and 20 matched subjects with classic PCOS and 10
      healthy control subjects. Hormonal parameters and ovarian blood flow by color
      flow Doppler imaging were obtained in the early follicular phase. RESULTS:
      Characteristic elevations in luteinizing hormone (LH) and androgens were found in
      both groups with PCOS compared with control groups. Women with anovulatory PCOS
      had high insulin levels and lower Quantitative Insulin-Sensitivity Check Index
      (QUICKI) values compared with women with ovulatory PCOS, although both groups had
      values that were different from healthy control subjects (P<.01). Ovarian volume
      was similar in the two groups with PCOS, but pulsatility and resistance indices
      were lower in anovulatory PCOS (P<.01) compared with ovulatory PCOS and control
      subjects, who had similar findings. Insulin correlated negatively with the
      resistance index and QUICKI correlated positively (r=0.653, P<.01). There was a
      negative correlation between the resistance index and unbound testosterone (r=
      0.5, P<.05). CONCLUSION: These data suggest that differences in ovarian blood
      flow in anovulatory versus ovulatory women with PCOS and that hormonal factors,
      including insulin resistance, may influence this relationship. The alterations in
      blood flow in anovulatory PCOS may contribute toward or result from anovulation.

PMID- 14634555
TI  - Serum antibody response to the heat shock protein 60 of Chlamydia trachomatis in
      women with developing cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to determine whether serum antibody
      response to the three versions of chlamydial heat shock protein 60 is associated
      with an increased risk for cervical cancer. STUDY DESIGN: Women with cervical
      carcinoma were identified by linking the data files of three Nordic serum banks
      with cancer registries. Overall, 178 women with invasive cervical carcinoma were
      identified. For each case, the earliest prediagnostic serum sample was chosen,
      and three matched control subjects who were free of cancer at the time of the
      case diagnosis were selected randomly. Serum antibodies to the chlamydial heat
      shock protein 60 were measured by enzyme-linked immunosorbent assay and
      correlated with the risk of the subsequent development of cervical cancer.
      RESULTS: Antibodies to chlamydial heat shock protein 60-1 were associated with
      cervical squamous cell carcinoma among cases with long lag time (>3.5 years; odds
      ratio, 2.4; 95% CI, 1.1-5.1). Antibodies to chlamydial heat shock protein 60-2 or
      chlamydial heat shock protein 60-3 were not associated with cervical cancer risk.
      CONCLUSIONS: The finding that chlamydial heat shock protein 60-1 antibodies are
      associated with an increased cervical cancer risk suggests that persistent
      Chlamydia trachomatis infection may contribute to cervical neoplasia.

PMID- 14634556
TI  - The ability of traditional vital signs and shock index to identify ruptured
      ectopic pregnancy.
AB  - OBJECTIVE: This study evaluated the correlation between vital signs and
      hemoperitoneum and the association between abnormal vital signs and tubal
      rupture. STUDY DESIGN: With the use of a retrospective case-control design, the
      initial heart rate, systolic blood pressure, and heart rate/systolic blood
      pressure were correlated with respect to degree of hemoperitoneum; predictive
      values were calculated. RESULTS: Fifty-two patients were studied (25 ruptured
      pregnancies and 27 unruptured ectopic pregnancies). Correlation coefficients were
      heart rate (r=0.50; 95% CI, 0.26-0.68), systolic blood pressure (r=-0.34; 95% CI,
      -0.56 to -0.08), and heart rate/systolic blood pressure (r=0.69; 95% CI, 0.51
      0.81). The sensitivity for heart rate, systolic blood pressure, and heart
      rate/systolic blood pressure was 28%, 36%, and 72% respectively; the specificity
      was 96%, 96%, and 67%, respectively. CONCLUSION: Normal vital signs alone are
      poor predictors of ruptured ectopic pregnancy; the heart rate/systolic blood
      pressure correlates best with the quantity of intraperitoneal hemorrhage.

PMID- 14634557
TI  - Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and
      flucytosine.
AB  - OBJECTIVE: The purpose of this study was to review the treatment outcome and
      safety of topical therapy with boric acid and flucytosine in women with Candida
      glabrata vaginitis. STUDY DESIGN: This was a retrospective review of case records
      of 141 women with positive vaginal cultures of C glabrata at two sites, Wayne
      State University School of Medicine and Ben Gurion University. RESULTS: The boric
      acid regimen, 600 mg daily for 2 to 3 weeks, achieved clinical and mycologic
      success in 47 of 73 symptomatic women (64%) in Detroit and 27 of 38 symptomatic
      women (71%) in Beer Sheba. No advantage was observed in extending therapy for 14
      to 21 days. Topical flucytosine cream administered nightly for 14 days was
      associated with a successful outcome in 27 of 30 of women (90%) whose condition
      had failed to respond to boric acid and azole therapy. Local side effects were
      uncommon with both regimens. CONCLUSIONS: Topical boric acid and flucytosine are
      useful additions to therapy for women with azole-refractory C glabrata vaginitis.

PMID- 14634558
TI  - Survival outcomes in patients with recurrent ovarian cancer who were treated with
      chemoresistance assay-guided chemotherapy.
AB  - OBJECTIVE: The purpose of this study was to determine the outcome of patients
      with recurrent ovarian carcinoma after extreme drug resistance assay-directed
      therapy. STUDY DESIGN: Fifty women who were treated with chemotherapy based on
      extreme drug resistance assay guidance were compared with 50 well-balanced
      control subjects who were treated empirically. RESULTS: In the platinum-sensitive
      group, patients with extreme drug resistance-directed therapy had an overall
      response rate of 65% compared with 35% in the patients who were treated
      empirically (P=.02). The overall and progression-free median survival were 38 and
      15 months in the extreme drug resistance assay group compared with 21 and 7
      months in the control group, respectively (P=.005, overall; P=.0002, progression
      free). In the platinum-resistant group, there was no improved outcome in the
      patients who underwent assay-guided therapy. In multivariate analysis, platinum
      sensitive disease, extreme drug resistance-guided therapy and early stage of
      disease were independent predictors for improved survival. CONCLUSION: In this
      retrospective analysis, our results indicate an improved outcome in patients with
      recurrent ovarian carcinoma who have platinum sensitive disease and who underwent
      extreme drug resistance-directed chemotherapy. Randomized, prospective,
      controlled trials are needed.

PMID- 14634559
TI  - Monochorionic pregnancy--where have we been? Where are we going?

PMID- 14634560
TI  - The management of acardiac twins: a conservative approach.
AB  - OBJECTIVE: Optimal management of acardiac twin pregnancies is controversial. Data
      suggest a 50% mortality rate in the "pump" twin when the pregnancy is managed
      expectantly. Because of increased antenatal diagnosis, outcomes in expectantly
      managed cases may be better than reported. Our objective was to determine the
      outcome of expectantly managed acardiac twin pregnancies. STUDY DESIGN: All cases
      of antenatally diagnosed acardiac twins delivered in our community between 1994
      and 2001 were ascertained. All were managed expectantly. Perinatal outcome of
      pump twins was the primary outcome variable. RESULTS: Ten cases were identified.
      Nine women were delivered of healthy pump twins. There was one neonatal death.
      The mean gestational age at delivery was 34.2 weeks. The mean weights of the pump
      and acardiac twins were 2279 g and 1372 g, respectively. CONCLUSION: Neonatal
      mortality of pump twins in antenatally diagnosed acardiac twin pregnancies may be
      considerably less than reported. Expectant management with close antepartum
      surveillance deserves consideration.

PMID- 14634561
TI  - Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine the long-term
      neurodevelopmental outcome in children after twin-to-twin transfusion syndrome.
      STUDY DESIGN: Maternal and neonatal medical records of all twin-to-twin
      transfusion syndrome patients who were admitted to our center between 1990 and
      1998 were reviewed. Neurologic and mental development at school age was assessed
      during a home visit in all twin-to-twin transfusion syndrome survivors. RESULTS:
      A total of 33 pregnancies with twin-to-twin transfusion syndrome were identified.
      Four couples opted for termination of pregnancy. All other pregnancies were
      treated conservatively, 18 pregnancies (62%) with serial amnioreductions and 11
      pregnancies (38%) without intrauterine interventions. Mean gestational age at
      delivery was 28.6 weeks (range, 20-37 weeks). The perinatal mortality rate was
      50% (29/58 infants). The birth weight of the donor twins was less than the
      recipient twins (P<.001). Systolic blood pressure at birth was lower in donors
      than in recipients (P=.023), and donors required inotropic support postnatally
      more frequently than did recipients (P=.008). The incidence of hypertension at
      birth was higher in recipients than in donors (P=.038). Abnormal cranial
      ultrasonographic findings were reported in 41% of the neonates (12/29 neonates).
      All long-term survivors (n=29 neonates) were assessed during a home visit. Mean
      gestational age at birth of the surviving twin was 31.6 weeks (range, 25-37
      weeks). The mean age at follow-up was 6.2 years (range, 4-11 years). The
      incidence of cerebral palsy was 21% (6/29 infants). Five of 6 children with
      cerebral palsy had an abnormal mental development. The incidence of cerebral
      palsy in the group of survivors who were treated with serial amnioreduction was
      26% (5/19 infants). Four children were born after the intrauterine fetal demise
      of their co-twin, 2 of which had cerebral palsy. CONCLUSION: The incidence of
      adverse neurodevelopmental outcome in twin-to-twin transfusion syndrome survivors
      is high, especially after the intrauterine fetal demise of a co-twin.

PMID- 14634562
TI  - The value of middle cerebral artery peak systolic velocity in the diagnosis of
      fetal anemia after intrauterine death of one monochorionic twin.
AB  - OBJECTIVE: The purpose of this study was to assess the value of the fetal middle
      cerebral artery peak systolic velocity in the prediction of anemia within 24
      hours of the death of one monochorionic twin in twin-to-twin-transfusion syndrome
      and to establish the correlation between middle cerebral artery peak systolic
      velocity and hemoglobin concentration in fetuses who are at risk for acute
      anemia. STUDY DESIGN: Doppler examination of the middle cerebral artery peak
      systolic velocity was performed in 20 monochorionic survivors of pregnancies that
      were complicated by twin-to-twin-transfusion syndrome that occurred between 20
      and 34 weeks of gestation. Doppler examination was performed before cordocentesis
      and after intrauterine transfusion when appropriate. Both hemoglobin
      concentration and middle cerebral artery peak systolic velocity were expressed in
      multiples of the median. Severe anemia was defined as hemoglobin concentration of
      <0.55 multiples of the median, and we used the cutoff point of 1.50 times the
      median values at any gestational age to calculate the sensitivity and specificity
      of middle cerebral artery peak systolic velocity in detecting moderate or severe
      anemia. RESULTS: Fetal anemia was confirmed in 10 of 20 fetuses. We performed
      seven intrauterine transfusions. The sensitivity and specificity of middle
      cerebral artery peak systolic velocity in the prediction of severe fetal anemia
      were of 90%, with a false-negative rate of 10%. The correlation between peak
      systolic velocity and hemoglobin concentration both before and after transfusion
      was evaluated by regression analysis and was strongly significant. CONCLUSION: In
      fetuses who are at risk of acute anemia, the measurement of middle cerebral
      artery peak systolic velocity was found to be a reliable noninvasive diagnostic
      tool and may be helpful in counseling and planning invasive assessment.

PMID- 14634563
TI  - Monoamniotic-versus diamniotic-monochorionic twin placentas: anastomoses and twin
      twin transfusion syndrome.
AB  - OBJECTIVE: The purpose of this study was to compare monoamniotic-monochorionic
      and diamniotic-monochorionic twin placentas and to estimate the incidence of twin
      twin transfusion syndrome in monoamniotic-monochorionic twin pregnancies. STUDY
      DESIGN: We analyzed the angioarchitecture and cord insertion distance in 24
      monoamniotic-monochorionic and 200 diamniotic-monochorionic placentas. RESULTS:
      Compared with diamniotic-monochorionic placentas, monoamniotic-monochorionic
      placentas had significantly more arterioarterial anastomoses (20/20 vs 159/200,
      respectively; P=.013), significantly less opposite arteriovenous anastomoses
      (10/20 vs 165/200, respectively; P=.002), similar venovenous anastomoses (6/20 vs
      46/200, respectively; P=.323), and arteriovenous anastomoses (20/20 vs 187/200
      respectively; P=.279) and significantly shorter umbilical cord distances (median
      [+/-SD], 5.0+/-6.9 cm vs 17.5+/-6.8 cm; P<.001). CONCLUSION: Monoamniotic
      monochorionic and diamniotic-monochorionic placentas have different anastomotic
      patterns. The (virtually) 100% incidence of arterioarterial anastomoses in
      monoamniotic-monochorionic placentas explains the reason that twin-twin
      transfusion syndrome rarely occurs in monoamniotic-monochorionic twin pregnancies
      and predicts that twin-twin transfusion syndrome manifestations are approximately
      5 times less often recognized in monoamniotic-monochorionic pregnancies than in
      diamniotic-monochorionic pregnancies.

PMID- 14634564
TI  - Screening performance of first-trimester nuchal translucency for major cardiac
      defects: a meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the screening performance of
      increased first-trimester nuchal translucency for the detection of major
      congenital heart defects. STUDY DESIGN: A meta-analysis based on MEDLINE and
      EMBASE searches (up to June 2002) that assessed the diagnostic performance of
      increased nuchal translucency for congenital heart defect detection. Weighted
      sensitivity and specificity estimates (random effects) and summary receiver
      operating characteristic curves were obtained. RESULTS: Eight independent studies
      with 58,492 pregnant women were analyzed. There was significant heterogeneity
      among the studies. Nuchal translucency above the 99th percentile had a
      sensitivity of 31% and specificity of 98.7% (random effects calculations), with a
      positive likelihood ratio of 24. Summary receiver-operating characteristic
      estimates were consistent with these values. The ability of nuchal translucency
      measurements above this threshold to detect cardiac malformations varied
      nonsignificantly (P=.64) for different congenital heart defects types
      (sensitivity range, 25%-55%). CONCLUSION: Nuchal translucency screening is a
      modestly efficient strategy for congenital heart defect detection; the use of the
      99th percentile threshold may capture approximately 30% of congenital heart
      defects.

PMID- 14634565
TI  - Effects of maternal age and education on the pattern of prenatal testing:
      implications for the use of antenatal screening as a solution to the growing
      number of amniocenteses.
AB  - OBJECTIVE: This study was undertaken to assess age-specific effects of maternal
      education on patterns of prenatal testing. STUDY DESIGN: We used data from a
      sample of all births in France in 1998. Statistical analysis included logistic
      regression and likelihood ratio tests. RESULTS: The rate of amniocentesis of
      women without serum screening was 7.3% for those with 12 years or less, and 16.7%
      for those with more than 12 years of education. Women with lower levels of
      education were about 50% more likely to have an amniocentesis if they had serum
      screening (odds ratio [OR], 1.5; 95% CI, 1.2-1.8). In contrast, women with higher
      levels of education were less likely to have an amniocentesis with screening (OR,
      0.7; 95% CI, 0.6-0.8); the education effect persisted across maternal age groups.
      CONCLUSION: Many women eligible for reimbursed serum screening, in particular
      those with higher levels of education, obtain amniocentesis without serum
      screening. This might limit the use of antenatal screening as a solution to the
      growing number of amniocenteses.

PMID- 14634566
TI  - Low selenium status is associated with the occurrence of the pregnancy disease
      preeclampsia in women from the United Kingdom.
AB  - OBJECTIVE: Because the trace element selenium behaves as an antioxidant and
      peroxynitrite scavenger when incorporated into selenoproteins, our objective was
      to determine whether low selenium status was associated with a greater risk of
      occurrence of preeclampsia. STUDY DESIGN: Fifty-three preeclamptic patients and
      53 matched pregnant controls at the John Radcliffe Hospital, Oxford, gave
      clippings of their toenails (laid down from 3-12 months previously) for selenium
      determination by neutron activation analysis. Clinical characteristics of the
      women and their infants were recorded. Statistical analysis was by Wilcoxon
      signed rank test and odds ratios were calculated by the ratio of discordant
      pairs. RESULTS: Median toenail selenium concentrations in the preeclamptic
      subjects were significantly lower than in their matched controls (P=.001). Being
      in the bottom tertile of toenail selenium was associated with a 4.4-fold (95% CI
      1.6-14.9) greater incidence of the condition. Within the preeclamptic group,
      lower selenium status was significantly associated (P=.029) with more severe
      expression of disease, as measured by delivery before 32 weeks. CONCLUSION: In
      the light of the reduction in selenium status in a number of European countries
      in recent years, this study raises the question of whether a small increase in
      selenium intake might help prevent preeclampsia in susceptible women.

PMID- 14634567
TI  - Diffusion imaging may predict reversible brain lesions in eclampsia and severe
      preeclampsia: initial experience.
AB  - OBJECTIVE: The purpose of this study was to validate diffusion-weighted magnetic
      resonance imaging in the prediction of the evolutive course of brain edema and to
      establish its pathophysiologic presence in patients with eclampsia/severe
      preeclampsia. STUDY DESIGN: Seventeen patients with a clinical diagnosis of
      severe eclampsia/preeclampsia and T2 hyperintense brain lesions on routine
      magnetic resonance imaging were evaluated at hospital admission and 8 weeks
      later. RESULTS: Brain edema was reversible in 13 patients and irreversible in 4
      patients, as indicated on follow-up magnetic resonance imaging. Sixteen of 17
      patients were differentiated accurately into reversible and irreversible groups
      on the basis of diffusion imaging on hospital admission. Diffusion-weighted
      magnetic resonance imaging demonstrated a significant increase in water mobility
      in abnormal regions compared with normal-appearing brains in patients in the
      reversible group (1.34+/-0.10 mm(2) vs 0.79+/-0.08 mm(2)/s x 10(-3), P<.001). In
      the irreversible group, restricted water diffusion was present, which was
      consistent with cytotoxic edema and early brain infarction in 3 of 4 patients.
      CONCLUSION: Diffusion-weighted magnetic resonance imaging can predict
      successfully the evolutive course of brain edema in an acute setting in these
      patients. Our findings indicate that brain edema is vasogenic, although
      ischemic/cytotoxic edema was observed less commonly.

PMID- 14634568
TI  - Elevation of serum macrophage colony-stimulating factor before the clinical
      manifestations of preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine whether the increase in
      serum macrophage colony-stimulating factor (M-CSF) levels preceded the onset of
      preeclampsia. STUDY DESIGN: We selected 146 women, of whom 36 were nonpregnant
      women participating in the preliminary study and 110 were normotensive pregnant
      women at risk for preeclampsia who were carrying single fetuses at about 18 weeks
      of gestation. The blood was collected and serum was stored at -20 degrees C until
      assay. Sixteen women had preeclampsia develop at a later stage of pregnancy
      (preeclamptics), whereas 89 women continued to have normotensive pregnancies
      until delivery. Thirty-five of the 89 women with normotensive pregnancy who were
      matched for age and parity were selected to form a control group (controls).
      Serum M-CSF levels were determined by the sandwich enzyme-linking immunosorbent
      assay method with use of three antibodies. RESULTS: Serum level of M-CSF was 1295
      U/mL (median) in preeclamptics and 957 U/mL in controls. Serum M-CSF levels were
      significantly higher (P<.0001) in preeclamptics than in controls. CONCLUSION: The
      increase in serum M-CSF levels markedly precedes the development of clinical
      manifestations of preeclampsia. Elevation of serum M-CSF supports M-CSF elevation
      in the placenta. This elevation at 18 weeks of gestation may be related to
      placental hypoxia, which is considered the cause of preeclampsia.

PMID- 14634569
TI  - Prediction of successful induction of labor at term: role of clinical history,
      digital examination, ultrasound assessment of the cervix, and fetal fibronectin
      assay.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether biochemical (fetal
      fibronectin assay) or biophysical (cervical assessment by transvaginal
      ultrasound) tests may have more value than digital examination in predicting
      successful induction of labor at term. STUDY DESIGN: The study enrolled
      prospectively 134 women undergoing labor induction at term caused by several
      obstetric conditions. All participants submitted to digital examination, fetal
      fibronectin assay, and transvaginal ultrasound for measurement of the cervical
      length and detection of funneling. The performance of each test in predicting
      delivery within 24 hours of labor induction was evaluated. Cox multiple
      regression analysis was performed to identify, among clinical and laboratory
      tests, which variables were independently associated with the duration of the
      latent phase and with the total duration of induced labor. RESULTS: The
      likelihood ratios for positive results (predicting that delivery would occur
      within 24 hours) were 6.61 (95% CI, 1.7-25.8) for a positive obstetric history
      (previous vaginal delivery), 2.61 (95% CI, 1.6-4.3) for a "favorable" digital
      examination, 1.41 (95% CI, 0.9-2.2) for a positive fetal fibronectin test, 1.61
      (95% CI, 0.9-3.0) for cervical length, and 2.20 (95% CI, 1.1-4.4) for the
      presence of funneling at transvaginal ultrasound. The likelihood ratios for
      negative results were 1.81 (1.3-2.5) for obstetric history, 4.34 (2.5-7.7) for
      digital examination, 1.41 (0.9-2.1) for fetal fibronectin, 1.29 (1.0-1.7) for
      cervical length, and 1.48 (1.1-2.0) for funneling. On multiple regression, the
      only variables independently associated with the duration of the latent phase and
      with the total duration of induced labor were obstetric history and digital
      examination. CONCLUSION: Only obstetric history and digital examination predicted
      accurately vaginal delivery within 24 hours and were independently associated
      with labor duration. Fetal fibronectin and ultrasound measurements failed to
      predict accurately the outcome of induced labor.

PMID- 14634570
TI  - Vaginal fetal fibronectin as a predictor of spontaneous preterm delivery in the
      patient with cervical cerclage.
AB  - OBJECTIVE: The purpose of this study was to assess the validity of vaginal fetal
      fibronectin as a screening test for spontaneous preterm birth in patients with
      cervical cerclage. STUDY DESIGN: A historic cohort of 117 patients who underwent
      cervical cerclage placement between 1996 and 2002 were identified. All patients
      were followed up in a maternal-fetal medicine faculty practice in a university
      setting. Serial fetal fibronectin samples of vaginal secretions were collected
      every 2 to 3 weeks, starting at 22 weeks of gestation and continuing until 32
      weeks or delivery, whichever came first. RESULTS: There were 81 singleton, 23
      twin, 12 triplet, and 1 quadruplet pregnancies. There were 61 ultrasound
      indicated, 47 prophylactic, and 9 emergency cerclages that were placed. Most
      cerclages were of the modified Shirodkar type (95%) with a median gestational age
      at cerclage placement of 16.6 weeks. Overall, 33.3% of gestations were delivered
      spontaneously before 37 weeks of gestation; 17.1% of gestations were delivered
      spontaneously before 34 weeks. For deliveries within 2 weeks and 3 weeks of a
      single fetal fibronectin assessment, the test had a sensitivity of 50% and 48.3%,
      a specificity of 90% and 91.1%, a positive predictive value of 16.3% and 28.6%,
      and a negative predictive value of 97.9% and 96%, respectively. Subgroup analysis
      by number of fetuses (singleton, twin, and higher order multiple gestations)
      revealed similar values. For delivery before 34 weeks of gestation, fetal
      fibronectin had a sensitivity of 50%, a specificity of 78.4%, a positive
      predictive value of 33.3%, and a negative predictive value of 88%. CONCLUSION:
      This study is the first to evaluate the use of vaginal fetal fibronectin
      assessments to screen for preterm birth in patients who had undergone cervical
      cerclage procedures. We conclude that this test has similar validity to predict
      spontaneous preterm delivery in these high-risk pregnancies, as in previously
      published cohorts.

PMID- 14634571
TI  - Prospective comparative study of the safety and effectiveness of ginger for the
      treatment of nausea and vomiting in pregnancy.
AB  - OBJECTIVES: The primary objective of our study was to examine the safety and the
      secondary objective was to examine the effectiveness of ginger for nausea and
      vomiting of pregnancy (NVP). STUDY DESIGN: Pregnant women who called the
      Motherisk Program who were taking ginger during the first trimester of pregnancy
      were enrolled in the study. The women were compared with a group of women who
      were exposed to nonteratogenic drugs that were not antiemetic medications. The
      women were followed up to ascertain the outcome of the pregnancy and the health
      of their infants. They were also asked on a scale of 0 to 10 how effective the
      ginger was for their symptoms of NVP. RESULTS: We were able to ascertain the
      outcome of 187 pregnancies. There were 181 live births, 2 stillbirths, 3
      spontaneous abortions, and 1 therapeutic abortion. The mean birth weight was
      3542+/-543 g, the mean gestational age was 39+/-2 weeks, and there were three
      major malformations. There were no statistical differences in the outcomes
      between the ginger group and the comparison group with the exception of more
      infants weighing less than 2500 g in the comparison group (12 vs 3, P < or
      =.001). There were a total of 66 completed effectiveness scores with the mean
      score of 3.3+/-2.9 SD. CONCLUSION: These results suggest that ginger does not
      appear to increase the rates of major malformations above the baseline rate of 1%
      to 3% and that it has a mild effect in the treatment of NVP.

PMID- 14634572
TI  - Pregnancy outcomes in patients after radical trachelectomy.
AB  - OBJECTIVES: This study was undertaken to review and analyze the fertility and
      pregnancy outcomes in patients who have undergone radical trachelectomy as the
      method of management of invasive carcinoma of the cervix. STUDY DESIGN: All
      preoperative, operative, and follow-up data were collected prospectively.
      Perinatal information was completed by chart reviews and patient questionnaires.
      RESULTS: Of 80 patients having undergone the above procedure, 39 have attempted
      to conceive for a median of 11 months (range 1-85). There have been a total of 22
      pregnancies in 18 patients (4 patients pregnant twice). Of the 22 pregnancies, 18
      were viable, with 12 progressing to term and delivering by caesarean section.
      Preterm premature rupture of membranes was the primary cause of preterm delivery.
      CONCLUSION: This series confirms that pregnancy is a safe and realistic outcome
      for women undergoing radical trachelectomy for invasive carcinoma of the cervix.
      Given the apparently high incidence of preterm premature rupture of membranes,
      these pregnancies should be managed as high risk.

PMID- 14634573
TI  - Screening for gestational diabetes mellitus by a model based on risk indicators:
      a prospective study.
AB  - OBJECTIVE: This study was performed to prospectively evaluate a screening model
      for gestational diabetes mellitus on the basis of clinical risk indicators. STUDY
      DESIGN: In a prospective multicenter study with 5235 consecutive pregnant women,
      diagnostic testing with a 2-hour 75-g oral glucose tolerance test was routinely
      performed in women with risk indicators and offered to women without risk
      indicators as part of the study. RESULTS: Forty-four percent of the women
      underwent testing, 43% declined participation, 6% did not speak Danish, and 7%
      could not be contacted. By extrapolation of the results from tested women to the
      whole group in question, a 2.4% prevalence of gestational diabetes mellitus was
      calculated. Sensitivity and specificity of the model was 80.6 (73.7-87.6) and
      64.8 (63.5-66.1), respectively (95% CIs). CONCLUSION: Under ideal conditions,
      sensitivity of the model was comparable with universal screening by fasting
      glucose or a 1-hour 50-g glucose challenge test. Both screening and diagnostic
      testing could be avoided in two thirds of all pregnant women.

PMID- 14634574
TI  - Intra-amniotic corticosteroids for preterm lung maturation in sheep.
AB  - OBJECTIVE: The purpose of this study was to compare efficacy on fetal lung
      maturation of intra-amniotic betamethasone or budesonide with the efficacy of
      maternal intramuscular betamethasone. STUDY DESIGN: Pregnant ewes received intra
      amniotic betamethasone (0.5 mg/kg or 2 mg/kg fetal weight), intra-amniotic
      budesonide (0.5 mg/kg or 2 mg/kg), maternal intramuscular betamethasone (0.5
      mg/kg maternal weight), intra-amniotic saline solution, or maternal saline
      solution. Lambs were delivered 2 or 7 days later, at 124 days of gestation for
      measurement of respiratory system compliance, ventilatory efficiency index, and
      surfactant levels. RESULTS: Lung function increased 2 days after maternal
      betamethasone, intra-amniotic betamethasone (2 mg/kg), and intra-amniotic
      budesonide (2 mg/kg) administration and 7 days after maternal betamethasone or
      intra-amniotic budesonide (2.0 mg/kg) administration. Lung function was not
      improved 7 days after intra-amniotic betamethasone (2.0 mg/kg) administration or
      2 days after intra-amniotic betamethasone (0.5 mg/kg) or intra-amniotic
      budesonide (0.5 mg/kg) administration. Intra-amniotic corticosteroid
      administration increased fetal death and respiratory morbidity. CONCLUSION: Intra
      amniotic corticosteroid administration improved preterm lung function, but the
      associated morbidity and mortality rates suggest that they are not suitable for
      clinical use.

PMID- 14634575
TI  - Does external tocodynamometry increase maternal perception of uterine
      contractions?
AB  - A prospective study was performed on 63 women at risk for preterm delivery who
      recorded maternally perceived contractions for 1 hour before and after placement
      of an external tocodynamometer. Fifteen women had an increase, 11 had a decrease,
      and 37 had no change (P not significant) in the number of perceived contractions
      after placement of the tocodynamometer.

PMID- 14634576
TI  - Treatment of Trichomonas in pregnancy and adverse outcomes of pregnancy: a
      subanalysis of a randomized trial in Rakai, Uganda.
AB  - OBJECTIVE: The purpose of this study was to assess the association of presumptive
      Trichomonas vaginalis treatment during pregnancy and birth outcomes. STUDY
      DESIGN: A community-randomized trial of presumptive sexually transmitted disease
      treatment during pregnancy was conducted between 1994 and 1999 in Rakai district,
      Uganda. A subanalysis of a trial of presumptive therapy with azithromycin,
      cefixime, and metronidazole assessed Trichomonas vaginalis treatment in pregnant
      women. RESULTS: Children of 94 women with Trichomonas who were treated had
      increased low birth weight (relative risk, 2.49; 95% CI, 1.12-5.50), preterm
      birth rate (relative risk, 1.28; 95% CI, 0.81-2.02), and 2-year mortality rate
      (relative risk, 1.58; 95% CI, 0.99-2.52), compared with children of 112 women
      with Trichomonas who were not treated. CONCLUSION: Treatment of Trichomonas
      vaginalis during pregnancy may be deleterious, and we infer that this may be due
      to metronidazole. This is consistent with a National Institute for Child Health
      and Human Development trial that found an excess of preterm births in children of
      women with Trichomonas vaginalis infection who were treated with metronidazole.

PMID- 14634577
TI  - Three-dimensional color power imaging of the fetal hepatic circulation.
AB  - OBJECTIVE: The purpose of this study was to describe the use of three-dimensional
      power Doppler ultrasonography to identify vascular congenital anomalies of fetal
      portosystemic and umbilical venous systems. STUDY DESIGN: In a prospective study,
      the hepatic and umbilical venous systems were examined in 390 fetuses with two
      dimensional ultrasonography, color, and spectral Doppler imaging. Fetuses
      suspected to have anomalies of the portal system and ductus venosus were
      additionally examined with three-dimensional power Doppler ultrasonography.
      RESULTS: Vascular anomalies were identified in 8 fetuses (absent ductus venosus,
      n=4; direct connection between the umbilical vein and the right atrium, n=2; and
      direct connection between the umbilical vein and the inferior vena cava, n=2) out
      of the 310 in which the venous system could be adequately imaged
      (prevalence=2.6%). Three-dimensional power Doppler imaging showed the course of
      the umbilical vein, its relationship to the portosystemic circulation, and
      whether a ductus venosus was present. CONCLUSION: Three-dimensional power Doppler
      ultrasonography can be used to image normal fetal hepatic and portal circulation,
      as well as identify anomalies of the fetal portosystemic and umbilical venous
      systems.

PMID- 14634578
TI  - A comparative study of postnatal depression and its predictors in Taiwan and
      mainland China.
AB  - OBJECTIVE: The purpose of this study was to compare the prevalence and risk
      factors of postpartum depression in Taiwan and mainland China. STUDY DESIGN: A
      total of 512 mothers during the 6th postpartum week were recruited by means of
      convenience sampling from Kaohsiung City and Pingtung County aboriginal tribes in
      Taiwan and Fuzhou City in China. Five self-report instruments were used to
      collect data. RESULTS: Significant differences of stress, social support, self
      esteem, depression, and health-promoting lifestyles were found among the three
      groups. Stress, social support, and self-esteem were the significant predictors
      of postpartum depression for women living in Kaohsiung, Taiwan. Stress and self
      esteem were the significant predictors of postpartum depression for female
      aborigines living in Pingtung County, Taiwan. Education, social support, and self
      esteem were the significant predictors of postpartum depression for women living
      in Fuzhou, China. CONCLUSION: These findings serve as a reminder that when
      considering postpartum depression mechanisms, one should not disregard cultural
      mediators. Also, there is evidence that the new mother's self-esteem is
      transculturally important with regard to the susceptibility to postpartum
      depression.

PMID- 14634579
TI  - Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype
      influences midtrimester amniotic fluid concentrations of interleukin-1beta and
      interleukin-1 receptor antagonist and pregnancy outcome.
AB  - OBJECTIVE: Preterm labor in experimental models is initiated by intra-amniotic
      interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist
      (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated
      with variations in IL-1beta and IL-1ra production. The relationship among the IL
      1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second
      trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN:
      Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained
      at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations
      by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a
      length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction.
      Pregnancy outcomes were obtained after completion of testing. RESULTS: The
      distribution of fetal IL-1ra genotypes was similar to that found in other
      populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were
      IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes,
      whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2
      was associated with a greater than 50% increase in midtrimester intra-amniotic IL
      1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared
      with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2
      homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra,
      was related to an increased rate of preterm birth (P<.0001). In the 11
      pregnancies that were subsequently terminated because of major malformations,
      there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was
      unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2
      allele is associated with enhanced intraamniotic IL-1beta production. Induction
      of an intra-amniotic proinflammatory immune response might be more likely to lead
      to preterm labor in fetuses carrying the IL1RN*2 allele.

PMID- 14634580
TI  - Neurokinin B peptide serum levels are higher in normotensive pregnant women than
      in preeclamptic pregnant women.
AB  - OBJECTIVES: The purpose of this study was to examine neurokinin B levels in serum
      from preeclamptic and normotensive and to investigate the role of neurokinin B in
      preeclampsia. STUDY DESIGN: Peripheral and uterine venous blood neurokinin B
      levels were measured in 14 normotensive and 8 preeclamptic pregnant women by
      radioimmunoassay. RESULTS: Neurokinin B levels in normotensive women were 4.91 +/
      2.67 nmol/L in peripheral and 5.59 +/- 2.06 nmol/L in uterine blood. In pregnant
      women with preeclampsia, neurokinin B levels were 2.79 +/- 1.68 nmol/L and 3.20
      +/- 1.55 nmol/L, respectively. Neurokinin B levels were significantly higher in
      normotensive women (P=.032 in peripheral and P=.006 in uterine blood).
      CONCLUSIONS: Neurokinin B serum levels were higher in normotensive women. Higher
      neurokinin B concentrations in normotensive pregnant women may be due to the
      advanced gestational age and/or the result of a negative interaction of other
      vasoactive substances. The role of neurokinin B in preeclampsia remains to be
      determined.

PMID- 14634581
TI  - Composition of gestational weight gain impacts maternal fat retention and infant
      birth weight.
AB  - OBJECTIVE: The purpose of this study was to evaluate how changes in gestational
      weight and body composition affect infant birth weight and maternal fat retention
      after delivery in underweight, normal-weight and overweight women. STUDY DESIGN:
      We assessed the body composition of 63 women (low body mass index, 17 women;
      normal body mass index, 34 women; and high body mass index, 12 women) on the
      basis of measurements of total body nitrogen by prompt-gamma activation analysis,
      total body potassium by whole body counting, and a multicomponent model based on
      total body water by deuterium dilution, body volume by densitometry, and bone
      mineral content by dual energy x-ray absorptiometry (DXA) before pregnancy, at 9,
      22, and 36 weeks of gestation, and at 2, 6, and 27 weeks after delivery. Infant
      weight and length were recorded at birth; infant anthropometry and body
      composition by DXA were assessed at 2 and 27 weeks of age. RESULTS: Gestational
      weight gain was correlated significantly with gains in total body water, total
      body potassium, protein, fat-free mass, and fat mass (P=.001-.003). Gains in
      total body water, total body potassium, protein and fat-free mass did not differ
      among body mass index groups; however, fat mass gain was higher in the high body
      mass index group (P=.03). Birth weight was correlated positively with gain in
      total body water, total body potassium, and fat-free mass (P<.01), but not fat
      mass. Postpartum weight and fat retention were correlated positively with
      gestational weight gain (P=.001) and fat mass gain (P=.001) but not with total
      body water, total body potassium, or fat-free mass gain. CONCLUSION: Appropriate,
      but not excessive, gestational weight gain is needed to optimize infant birth
      weight and minimize maternal postpartum fat retention.

PMID- 14634582
TI  - Vaginal cytokines in normal pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine whether the vaginal
      cytokine concentration varies during the course of uncomplicated pregnancy. STUDY
      DESIGN: Prenatal visits of healthy women to University Hospital Gasthuisberg,
      Leuven, Belgium were considered. Cytokine levels in vaginal washings from 30
      unselected healthy women with uncomplicated pregnancies were monitored during
      pregnancy and compared with those from 62 nonpregnant healthy control subjects.
      Exclusion criteria included bacterial vaginosis, moderate or severe aerobic
      vaginitis, Trichomonas vaginalis, Candida vaginitis (wet mount or culture),
      gonorrhea, and Chlamydia. Interleukin-6, interleukin-8, interleukin-1beta,
      interleukin-1-receptor antagonist, leukemia inhibitory factor, and tumor necrosis
      factor were measured. Nonparametric Kruskal-Wallis and Welch tests were used for
      univariate analysis, and the Spearman rank test was used for multivariate
      analysis. RESULTS: Compared with concentrations in nonpregnant women, interleukin
      1beta concentrations were similar, but interleukin-1-receptor antagonist
      production was depressed throughout pregnancy. Vaginal interleukin-6 and
      interleukin-8 were less often discovered during pregnancy than outside pregnancy
      and dipped significantly in the middle trimester, to rise again to prepregnancy
      levels in the third trimester. Leukemia inhibitory factor was lower during the
      beginning of pregnancy (P=.038) but otherwise did not differ from nonpregnant
      values throughout pregnancy nor did tumor necrosis factor. Sexual activity could
      not explain these findings. CONCLUSION: Vaginal cytokine levels, especially
      interleukin-1 receptor antagonist, from pregnant women may differ from
      nonpregnant values; some levels, such as interleukin-6 and interleukin-8, may
      fluctuate during normal pregnancy. These spontaneous variations during pregnancy
      must be taken into account when mucosal immunologic responses to infection of the
      lower genital tract are being studied.

PMID- 14634583
TI  - Maternal plasma hypertonicity is accentuated in the postterm rat.
AB  - OBJECTIVE: In humans and rats, pregnancy-associated maternal plasma volume
      expansion and plasma hypotonicity may facilitate maternal-to-fetal water
      transfer. Although reduced amniotic fluid volume occurs commonly in postterm
      pregnancy, the mechanisms are unknown. We previously demonstrated a reversal of
      pregnancy-induced maternal plasma hypotonicity that occurs in the near term (20
      days) pregnant rats. We sought to determine whether the relative maternal plasma
      hypertonicity continues in the postterm period. STUDY DESIGN: Rat gestation
      (normal, 21 days) was prolonged with subcutaneous progesterone injection.
      Pregnant rats at gestation, 18 days, 21 days, and 24 days and nonpregnant rats
      were studied. Maternal and fetal hematocrit levels, plasma osmolality,
      electrolyte levels, and amniotic fluid volume were determined. In addition,
      maternal and fetal tissues were analyzed for water and electrolyte content.
      RESULTS: Compared with term (21days), postterm pregnant rats (24 days) had a
      significant increase in maternal and fetal plasma osmolality (293.7+/-1.4 mOsm/kg
      vs 302.8+/-3.7 mOsm/kg and 301.0+/-2.0 mOsm/kg vs 310.3+/-3.2 mOsm/kg,
      respectively; P<.01) and sodium and chloride concentrations. Conversely, both
      maternal and fetal hematocrit levels decreased significantly in the postterm
      period. Postterm rats demonstrated an increased fetal mortality rate (24%) and a
      significantly reduced amniotic fluid volume (4.2+/-0.6 mL vs 6.6+/-0.6 mL,
      P<.01). CONCLUSION: These results indicate that the near-term reversal of
      maternal plasma hypotonicity that has been observed previously is further
      accentuated in the postterm pregnancy. This continued hypertonicity may induce a
      fetal-to-maternal water flow and contribute to postterm oligohydramnios and
      increased fetal morbidity and mortality rates.

PMID- 14634584
TI  - A proinflammatory cytokine response is present in the fetal placental vasculature
      in placental insufficiency.
AB  - OBJECTIVE: Vascular disease in the umbilical placental circulation is associated
      with fetal growth restriction and adverse outcome. It may be identified
      antenatally by the study of umbilical artery Doppler flow velocity waveforms. The
      cause of this vascular disease is unknown. We have previously provided indirect
      evidence for endothelial cell activation and a proinflammatory cytokine response.
      Recently, a family of inhibitors of cytokine signaling has been identified,
      referred to as the suppressors of cytokine signaling (SOCS). Activation of SOCS
      occurs when cytokines are produced in stimulated cells. We tested the hypothesis
      that endothelial cell activation was present in umbilical placental vascular
      disease and was associated with production of proinflammatory cytokines and
      members of the family of SOCS. STUDY DESIGN: Placentas were collected at delivery
      and microvascular endothelial cells were isolated. We studied 13 normal
      pregnancies and 10 with umbilical placental vascular disease identified by an
      abnormal umbilical artery Doppler study. Placental pieces were digested with
      collagenase and purified by adherence to Dynabeads coated with monoclonal
      antibody against CD31. The RNA was extracted from isolated endothelial cells. The
      messenger RNA expression of cytokine production (interleukin-6 and interleukin-8)
      and the members of SOCS family (CIS, SOCS1, SOCS2, and SOCS3) were assessed by
      use of semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS:
      In the microcirculation of the placenta, endothelial cell expression of
      interleukin-6 messenger RNA (2.50+/-0.60 vs 1.25+/-0.26) and interleukin-8
      messenger RNA (2.83+/-0.55 vs 1.58+/-0.27) was up-regulated in umbilical
      placental vascular disease in comparison to normal pregnancy. The endothelial
      cell mRNA expression of SOCS2 (3.36+/-0.77 vs 1.76+/-0.29) and SOCS3 (2.77+/-0.60
      vs 1.48+/-0.26) was enhanced in placental vascular disease. There was no
      significant difference in expression of CIS and SOCS1 in microvessel endothelial
      cells. CONCLUSION: We have demonstrated that microvessel endothelium of the fetal
      placental vasculature produces both the proinflammatory cytokines (interleukin-6
      and interleukin-8) and members of SOCS family (SOCS2 and SOCS3) in umbilical
      placental vascular disease. This cytokine production may play a key role in the
      interaction of endothelial cells of the placenta villi with neighboring cells.
      The up-regulation of SOCS2 and SOCS3 indicates these are the major negative
      regulators in umbilical placental microvessel endothelial cell activation
      pathways. By its occurrence, this also confirms the presence of a proinflammatory
      cytokine response.

PMID- 14634585
TI  - Effects from prenatal exposure to alprazolam on the social behavior of mice
      offspring.
AB  - OBJECTIVE: The purpose of this study was to conduct, in a randomized placebo
      controlled manner, social behavior testing on mice offspring that were exposed
      prenatally to alprazolam. STUDY DESIGN: A previously described, clinically
      relevant dose of 0.32 mg/kg of alprazolam (n=8 mice) or a placebo (n=9 mice) was
      given to gravid C57BL/6 mice by gavage on gestational day 18. Social play,
      sleep/wake patterns, and male aggression of the exposed offspring were assessed
      during prejuvenile, juvenile, and adult periods. RESULTS: Alprazolam did not
      produce treatment differences in pregnancy outcomes or in dam-pup interactions.
      Compared with the placebo group, alprazolam-exposed offspring demonstrated less
      desire to escape (P<.01), more desire to remain alone (P<.02), and shorter
      periods of being awake (P<.03) on PND 17. Alprazolam-exposed male offspring
      exhibited more aggression on food restriction (P<.01) and on cage changing
      (P<.01). CONCLUSION: Mice offspring that were exposed prenatally to alprazolam
      demonstrated more individual rather than group activities, avoidance of open
      areas, and aggression in males. Correlation of these findings in humans is
      encouraged.

PMID- 14634586
TI  - Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in
      sheep.
AB  - OBJECTIVE: Intra-amniotic administration of endotoxin in sheep is a model of
      subclinical chorioamnionitis. Intrauterine inflammation alters lung development
      to improve postnatal lung function and may predispose the infant to lung and
      brain injury. We describe the effects of intra-amniotic endotoxin on cytokines
      and white cell responses in the membranes and amniotic fluid and investigate the
      hypothesis that betamethasone treatment suppresses these responses. STUDY DESIGN:
      Pregnant ewes were allocated at random to receive either intra-amniotic saline
      solution (control animals), maternal intramuscular betamethasone, intra-amniotic
      endotoxin by ultrasound guidance (10 mg Escherichia coli 055:B5), or a
      combination of the betamethasone and endotoxin treatments. Lambs were delivered
      abdominally at 110 to 125 days of gestation at time points that ranged from 2
      hours to 15 days after treatment. RESULTS: When compared with saline solution
      injected control animals, the intra-amniotic injection of endotoxin increased
      white cell counts in amniotic fluid. Levels of interleukin-8, but not interleukin
      6, were significantly increased in amniotic fluid from 5 hours to 15 days after
      intra-amniotic endotoxin injection, and interleukin-8 levels were not decreased
      by concurrent treatment with betamethasone. After endotoxin treatment,
      interleukin-1beta and interleukin-8 messenger RNA were expressed in chorion, and
      interleukin-6 messenger RNA expression was localized to chorionic blood vessel
      epithelium. The half-life of endotoxin in the amniotic fluid was 1.7 days, and
      levels remained measurable 15 days after injection. CONCLUSION: These findings
      confirm that the fetus can survive within amniotic fluid that contains endotoxin,
      white cells, and cytokines for periods of weeks or more. Betamethasone treatment
      can suppress the initial inflammation in the amnion-chorion, but interleukin-8
      levels and inflammatory cells in amniotic fluid were not suppressed 5 and 15 days
      after betamethasone treatment, presumably because of the slow clearance of
      bioactive endotoxin from the amniotic fluid.

PMID- 14634587
TI  - Effect of dexamethasone on pulmonary and renal angiotensin-converting enzyme
      concentration in fetal sheep during late gestation.
AB  - OBJECTIVES: The effect of dexamethasone on tissue angiotensin-converting enzyme
      (ACE) was investigated in fetal sheep. STUDY DESIGN: Pulmonary and renal ACE
      concentrations were measured in 16 sheep fetuses at between 127 and 131 days of
      gestation (term 145+/-2 days): 6 were untreated, whereas 10 were chronically
      catheterized and infused intravenously with either saline solution (0.9%, n=4) or
      dexamethasone (45-60 microg. kg(-1). d(-1), n=6) for the previous 2 days. The
      dexamethasone dose increased plasma dexamethasone to around one fifth of that
      measured in newborn human infants delivered after maternal dexamethasone
      treatment. RESULTS: Over the period of infusion, arterial blood pressure
      increased significantly in the dexamethasone (+6.8+/-1.5 mm Hg, P<.05) but not
      saline-treated fetuses (+1.6+/-0.6 mm Hg). At delivery, pulmonary ACE in the
      dexamethasone-infused fetuses (1.24+/-0.26 nmoles hippurate. min(-1). mg protein(
      1)) was significantly greater than in the control fetuses (0.50+/-0.07 nmoles.
      min(-1). mg protein(-1), P<.005); renal ACE was unchanged by dexamethasone
      treatment. Overall, pulmonary ACE and blood pressure were correlated on the last
      day of infusion (r=0.70, P<.05). CONCLUSION: The rise in pulmonary ACE seen in
      dexamethasone-treated sheep fetuses may contribute, in part, to the
      glucocorticoid-induced increase in blood pressure.

PMID- 14634588
TI  - Human umbilical vein vasoconstriction induced by epinephrine acting on alpha1B
      adrenoceptor subtype.
AB  - OBJECTIVE: Our purpose was to determine the presence of alpha(1)-adrenoceptor
      messenger RNA subtypes and extend the pharmacologic characterization of alpha(1)
      adrenoceptors involved in human umbilical vein (HUV) contraction. STUDY DESIGN:
      Cords (n=124) from healthy patients after term vaginal or cesarean deliveries
      were used. The vein was carefully dissected out of cords and used for reverse
      transcription combined with polymerase chain reaction (RT-PCR) to amplify
      alpha(1)-adrenoceptor transcripts. In isolated organ baths, HUV rings were
      mounted and cumulative concentration-response curves were constructed either for
      epinephrine or the selective alpha(1A)-adrenoceptor agonist, A-61603. In other
      series of experiments, the effects of the selective alpha(1A)- and alpha(1B)
      adrenoceptor antagonists (RS-100329 or B8805-033 or spiperone, AH11110A and
      cyclazosin, respectively) were evaluated to estimate its blocking potencies on
      epinephrine concentration-response curves. RESULTS: By means of RT-PCR technique
      alpha(1a)- and alpha(1b)-adrenoceptor transcripts were detected in the HUV. The
      blocking potency values of RS-100329 or B8805-033 against responses mediated by
      epinephrine were not consistent with the activation of an alpha(1A)-adrenoceptor
      population. Moreover, the low potency of the agonist A-61603 was not in
      accordance with an alpha(1A)-adrenoceptor interaction. On the other hand, the
      antagonist potencies of spiperone, AH11110A and cyclazosin were in agreement with
      an interaction on alpha(1B)-adrenoceptor subtype. CONCLUSION: Although alpha(1a)-
      and alpha(1b)-adrenoceptor messenger RNAs are detected in the HUV, only alpha(1B)
      adrenoceptors are involved in epinephrine vasoconstrictor action.

PMID- 14634589
TI  - Mapping of zones of altered morphology and chorionic connective tissue cellular
      phenotype in human fetal membranes (amniochorion and decidua) overlying the lower
      uterine pole and cervix before labor at term.
AB  - OBJECTIVE: The purpose of this study was to determine the location, frequency,
      and extent of altered fetal membrane morphology before term labor and its
      relation to myofibroblast activation in their connective tissue layers. STUDY
      DESIGN: Fetal membranes that were obtained from 10 women who underwent prelabor
      cesarean delivery at 38 to 39 weeks of gestation underwent biopsy examination
      with respect to the internal os of the cervix. The thickness of their constituent
      layers was measured, and the numbers of alpha-smooth muscle actin immunoreactive
      cells (ie, marker of myofibroblast activation) within the reticular layer were
      counted. RESULTS: A region that measured 119+/-21cm(2), that exhibited altered
      morphology of the fetal membranes from the lower uterine pole, and that was
      characterized by increased connective tissue thickness and decreased thickness of
      the cellular layers was demonstrated in all patients. In 8 of 10 patients, this
      region was centered on the location of the Babcock tissue forceps. Within this
      region was an area of fetal membranes that exhibited alpha-smooth muscle actin
      immunoreactivity in the cells of the reticular layer and whose number correlated
      with parameters of altered morphology. CONCLUSION: All patients before labor at
      term possess an area of fetal membranes that are located in the lower uterine
      pole that exhibit altered morphology that is associated with myofibroblastic
      activation in the chorionic connective tissue.

PMID- 14634590
TI  - Induction of localized differences in rat uterine radial artery behavior and
      structure during gestation.
AB  - OBJECTIVES: The objectives of this study were to investigate differences in
      diameter and vasoconstriction of premyometrial versus uteroplacental radial
      arteries and to evaluate the contribution of nitric oxide (NO) to myogenic tone
      as a function of vessel location. STUDY DESIGN: Radial arteries supplying either
      the myometrium or placenta were dissected from the uterus of pregnant rats.
      Constrictor responses to pressure elevation were studied before and after
      inhibition of endothelial NO synthase (eNOS). RESULTS: Passive lumen diameters of
      premyometrial and proximal uteroplacental arteries were comparable and
      significantly smaller than those of distal uteroplacental vessels. High potassium
      and pressure-induced responses were also similar in premyometrial and proximal
      but were virtually absent in distal uteroplacental segments. L-NNA enhanced
      pressure-induced tone, but was without effect in distal uteroplacental segments.
      CONCLUSION: Gestational remodeling alters arterial structure and reactivity in a
      highly localized manner. During pregnancy, enhanced basal production of NO may be
      an important local mechanism for uterine blood flow regulation.

PMID- 14634591
TI  - The effect of an elevated maternal lysine concentration on placental lysine
      transport in pregnant sheep.
AB  - OBJECTIVES: In a previous study, the coinfusion into the maternal circulation of
      lysine and several other amino acids failed to increase significantly lysine
      umbilical uptake. The purpose of this study was to determine whether umbilical
      lysine uptake can be increased by infusing a lysine solution that does not
      contain any other amino acid. STUDY DESIGN: Six late-gestation ewes were studied
      on 2 consecutive days. Samples were collected in both the control (first day) and
      experimental (second day) periods simultaneously from the maternal artery,
      uterine vein, fetal artery, and umbilical vein. In the control period, L-[1
      (13)C] lysine was infused into the maternal circulation. During the experimental
      period, both L-[1-(13)C] lysine and L-(12)C lysine were infused to increase
      maternal lysine concentration. Uterine and umbilical blood flows were measured by
      the steady state diffusion technique. Uterine and umbilical uptake of lysine and
      of alpha-aminoaminoadipic acid (AAD, a biproduct of lysine oxidation) were
      calculated. RESULTS: In response to a 2.7-fold increase in maternal lysine
      concentration (P<.001), fetal lysine concentration increased approximately 70%
      (P<.05) and umbilical uptake 50% (P<.05). In the experimental period, there was a
      significant (P<.05) placental uptake of fetal AAD, and the fetal/maternal plasma
      (13)C-lysine-specific activity ratio increased from 0.221+/-0.026 to 0.294+/
      0.029 (P<.05). In response to the increase in maternal lysine concentration, the
      maternal and fetal concentrations of several other amino acids were significantly
      decreased. CONCLUSION: This study establishes that the umbilical uptake of lysine
      can be increased by infusing lysine in the maternal circulation. However, the
      lysine infusion is associated with a decrease in the maternal concentration and
      umbilical uptake of other essential amino acids. These data, compared with the
      results of previous studies, indicate that attempts to increase the fetal uptake
      of an amino acid via maternal infusion may decrease the uptake of other amino
      acids by decreasing their maternal concentration and by inhibition of placental
      transport.

PMID- 14634592
TI  - Expression and regulation of the rat prostaglandin E2 receptor type 4 (EP4) in
      pregnant cervical tissue.
AB  - OBJECTIVE: Prostaglandins play an important role in the regulation of parturition
      and cervical ripening. Prostaglandin E(2) (PGE(2))-induced tissue remodeling is
      mediated through activation of prostaglandin E(2) receptor type 4 (EP4). EP4 is
      known to regulate matrix metalloproteinase secretion and expression and therefore
      may play a role in cervical ripening. We hypothesized that EP4 expression is
      regulated in the rat cervix to coincide with cervical ripening. In addition, we
      analyzed transcriptional regulation of the rat EP4 gene. STUDY DESIGN: EP4
      expression was evaluated in the cervix in timed pregnancy Sprague-Dawley rats by
      real-time reverse transcriptase polymerase chain reaction and Western blot. The
      genomic structure of the rat EP4 gene was determined by sequencing rat genomic
      clones obtained by plaque hybridization. Northern blots were performed to
      identify the number of different transcripts. The transcriptional start site was
      identified on the basis of sequence comparison to the human and mouse EP4 gene.
      The minimal promoter was identified by using reporter constructs containing
      portions of the 5' flanking region. Reporter activity was evaluated in vitro.
      Identified regulatory regions were mutated to determine their role in
      transcription. RESULTS: Cervical EP4 expression (messenger RNA and protein) peaks
      on the day of parturition. The rat EP4 gene is structurally similar to other
      prostaglandin receptors as well as the human EP4 gene and contains three exons
      separated by two introns. The coding regions are located in the second and third
      exons separated in the sixth transmembrane spanning region. Northern blot
      identified a single EP4 transcript with an estimated size of 4 kb, indicating a
      single transcription initiation site. The first 80 bases of the 5' flanking
      region were required for constitutive expression of EP4. Expression was lost
      after mutation of the GC/Sp1 binding site located at position -78 to -66
      downstream from the transcription initiation site. Three Sp1 binding sites were
      identified and appear to cooperate to enhance EP4 transcription. CONCLUSION: EP4
      expression is regulated in the cervix and peaks on the day of parturition. The
      genomic structure of the human and rat EP4 gene is conserved between these two
      species. A GC rich/Sp1 binding site located within the first 80 bases of the
      transcription start site is important in transcription initiation of the EP4
      gene.

PMID- 14634593
TI  - Incidence of transient hypoxia and pulse rate reactivity during paramedic rapid
      sequence intubation.
AB  - STUDY OBJECTIVE: We determine the incidence of desaturation and pulse rate
      reactivity during paramedic rapid sequence intubation of patients with severe
      head injuries (Glasgow Coma Scale score <or=8). METHODS: Adult patients with
      severe head injuries had recording oximeter-capnometers applied before rapid
      sequence intubation. Desaturation was defined as a reduction in oxygen saturation
      (Spo(2)) to less than 90% from an initial Spo(2) of greater than or equal to 90%
      or a decrease from a baseline of less than 90%. Event records were analyzed with
      emergency medical services (EMS) run sheets and debriefing reports. RESULTS:
      Thirty-one (57%) of 54 patients demonstrated desaturation during rapid sequence
      intubation. Twenty-six (84%) of these 31 events occurred in patients whose
      initial Spo(2) value with basic airway skills was greater than or equal to 90%.
      The median duration of desaturation was 160 seconds (interquartile range 48 to
      272 seconds), and the median decrease in Spo(2) was 22%. Six (19%) patients
      experienced marked bradycardia (pulse rate <50 beats/min) during desaturation
      events. Paramedics described rapid sequence intubation as "easy" in 26 (84%) of
      31 patients with desaturation. CONCLUSION: Out-of-hospital rapid sequence
      intubation by paramedics was complicated by a concerning incidence of
      desaturation and bradycardia. Paramedic reports did not reflect the presence of
      these concerning derangements. Most patients had acceptable Spo(2) values before
      rapid sequence intubation. An effective strategy for preoxygenation is needed
      before it can be concluded that rapid sequence intubation is of value in the out
      of-hospital care of patients with serious closed head injury.

PMID- 14634594
TI  - Out-of-hospital rapid sequence intubation: are we helping or hurting our
      patients?

PMID- 14634595
TI  - Factors impeding dispatcher-assisted telephone cardiopulmonary resuscitation.
AB  - STUDY OBJECTIVE: Dispatcher-assisted telephone cardiopulmonary resuscitation
      (CPR) instruction can increase the proportion of sudden cardiac arrest victims
      who receive bystander CPR and has been associated with improved survival. Most
      sudden cardiac arrest victims, however, do not receive bystander CPR. The study
      objective was to examine factors that may impede implementation of telephone CPR.
      METHODS: We reviewed dispatcher audio recordings and emergency medical services
      reports for 404 cases of sudden cardiac arrest that occurred from July 1, 2000,
      to June 30, 2002, in the study county to assess the phase (1, instructions not
      offered; 2, instructions offered but declined; or 3, instructions offered and
      accepted but CPR not implemented) and specific factors within each phase that
      potentially impede telephone CPR. RESULTS: Twenty-five percent (99/404) of
      victims received bystander CPR without dispatch assistance, 34% (139/404)
      received telephone CPR, and 41% (166/404) did not receive bystander CPR. Each
      phase of telephone CPR process impeded the implementation of CPR: (1)
      instructions not offered in 48% (80/166); (2) instructions offered but declined
      in 31% (52/166); and (3) instructions offered and accepted but CPR not
      implemented in 21% (34/166). During the first phase, telephone CPR was
      potentially impeded most frequently because the victim was reported to have signs
      of life (51/80, 64%); during the second and third phases, telephone CPR was most
      often impeded because of bystander physical limitation (32/86, 37%). Emotional
      distress, disease transmission, disagreeable victim characteristics, or
      medicolegal concerns uncommonly impeded telephone CPR (10/86, 12%). CONCLUSION:
      Factors potentially impeding telephone CPR can be identified. Although many are
      logistically challenging, some may be addressable and hence provide opportunities
      to strengthen the chain of survival.

PMID- 14634596
TI  - Barriers to dispatcher-assisted telephone cardiopulmonary resuscitation.

PMID- 14634597
TI  - What is the rate of adverse events after oral N-acetylcysteine administered by
      the intravenous route to patients with suspected acetaminophen poisoning?
AB  - STUDY OBJECTIVE: We conduct a study to determine the rate of adverse events
      (anaphylactoid and cardiorespiratory) associated with the use of oral N
      acetylcysteine by the intravenous route for the treatment of suspected
      acetaminophen poisoning and to examine specific variables that may be associated
      with adverse events. METHODS: We conducted a retrospective medical record review
      with explicit criteria. All patients who received oral N-acetylcysteine by the
      intravenous route from September 1995 to September 2001 were included. Patients
      were identified by cross-matching 3 databases. Adverse events were divided into
      categories of cutaneous, systemic, or life threatening. Five reviewers abstracted
      charts by using a standardized data collection form. Interrater reliability was
      calculated by using 24 medical records abstracted by all 5 reviewers. RESULTS:
      There were 7 adverse events identified in 187 patients (3.7%; 95% confidence
      interval 1.0% to 6.5%). Six adverse events were cutaneous and responded rapidly
      to antihistamines. One adverse event was life threatening but not clearly related
      to N-acetylcysteine. A high rate of antihistamine exposure (53%) was identified
      before the administration of N-acetylcysteine. Interrater agreement was higher
      than 95%. CONCLUSION: Intravenous administration of an oral solution of N
      acetylcysteine is associated with a low rate of adverse events and should be
      considered for selected patients with suspected acetaminophen poisoning.

PMID- 14634598
TI  - Quetiapine poisoning: a case series.
AB  - STUDY OBJECTIVE: We describe the effects of quetiapine in overdose. METHODS:
      Quetiapine poisonings were identified from a prospective database of poisoning
      admissions to a regional toxicology service. Data extracted included details of
      ingestion, clinical features, investigations (including ECG), and other outcomes
      (length of stay and ICU admission rate). RESULTS: There were 45 cases of
      quetiapine overdose, of which 18 patients with quetiapine assay results were
      included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42
      hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested
      dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly
      correlated with estimated peak drug concentration (r(2)=0.84; P<.0001),
      confirming patient-provided history of ingestion. Seizures occurred in 2
      patients, delirium occurred in 3 patients, and mechanical ventilation was
      required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients
      ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were
      admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures
      occurred. For 10 patients for whom ECGs were available and who had ingested no
      cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the
      mean corrected QT (QTc) interval was increased at 487 ms, but the mean
      uncorrected QT interval was 349 ms. Reported dose and peak quetiapine
      concentrations were significantly associated with ICU admission and length of
      stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale
      score not less than 15 predicted patients not requiring ICU admission or length
      of stay more than 24 hours. CONCLUSION: Quetiapine overdose causes central
      nervous system depression and sinus tachycardia. In large overdoses, patients may
      require intubation and ventilation for associated respiratory depression.
      Although a prolonged QTc occurs, its clinical significance is unclear because it
      is most likely caused by an overcorrection caused by the tachycardia. In our
      experience, a reported dose of less than 3 g for patients who are not drowsy
      (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who
      did not coingest another toxic agent defined a group not requiring ICU admission
      or inpatient admission greater than 24 hours.

PMID- 14634599
TI  - Methylene 3, 4 dioxymethamphetamine-induced acute myocardial infarction.
AB  - Methylene 3, 4 dioxymethamphetamine (MDMA) has been gaining popularity as a
      recreational drug over the past few decades around the globe. Although once
      thought to be safer than its mother compound, amphetamine, several life
      threatening adverse reactions have been reported. Among the cardiovascular
      toxicities documented, MDMA commonly causes various forms of arrhythmia and heart
      failure. However, MDMA-induced acute myocardial infarction is rarely reported. We
      report a case of acute myocardial infarction in a young man shortly after taking
      MDMA. Massive thrombosis over the right coronary artery was demonstrated by means
      of emergency angiography. After treatment with intravenous glycoprotein IIb/IIIa
      inhibitor and intracoronary urokinase infusion, the coronary artery was shown to
      be patent without any apparent stenotic lesions. The mechanism of MDMA-induced
      acute myocardial infarction was discussed.

PMID- 14634600
TI  - Irukandji-like syndrome in South Florida divers.
AB  - Irukandji syndrome is a constellation of delayed severe local and systemic
      symptoms occurring after a Carukia barnesi box jellyfish sting involving any
      exposed skin. These cases are limited to Australia, the habitat of that animal.
      Numerous other cases of an Irukandji-like syndrome after other small Carybdeid
      genus envenomations have been reported elsewhere in the world. There have yet
      been no reports of Irukandji-like syndrome occurring in continental US coastal
      waters. We describe 3 cases of marine envenomation causing such a symptom complex
      in US military combat divers off Key West, FL. It is unclear what species caused
      the injuries, but a member of the Carybdeid genus seems most likely.

PMID- 14634601
TI  - Sedation for cardioversion in the emergency department: analysis of effectiveness
      in four protocols.
AB  - STUDY OBJECTIVE: We compare effectiveness, adverse effects, and recovery times of
      propofol, etomidate, and midazolam (with and without flumazenil) for
      cardioversion in the emergency department (ED). METHODS: Thirty-two
      hemodynamically stable adult patients undergoing cardioversion in the ED were
      randomly assigned to receive etomidate (n=9), propofol (n=9), midazolam (n=8), or
      midazolam followed by flumazenil (n=6). For all patients, we measured induction
      time, awakening time, total recuperation time, global time, and adverse effects.
      Arterial pressure, cardiac and respiratory rate, and peripheral oxygen saturation
      were monitored throughout the procedure. Descriptive and nonparametric tests were
      used. RESULTS: Demographic data were similar in all groups. Deep sedation and
      successful cardioversion were achieved in all cases. Hemodynamic assessment at
      baseline, after induction, after cardioversion, and at recovery demonstrated no
      significant difference between the 4 groups. Induction time was short in all
      groups. Awakening time was longer in the midazolam group (median 21 minutes,
      range 1 to 42 minutes) compared with that of the other groups (etomidate group:
      median 9.5 minutes, range 5 to 11 minutes; propofol group: median 8 minutes,
      range 3 to 15 minutes; midazolam/flumazenil group: median 3 minutes, range 2 to 5
      minutes), and the same occurred with total recuperation time (etomidate group:
      median 14 minutes, range 5 to 20 minutes; propofol group: median 10 minutes,
      range 5 to 15 minutes; midazolam group: median 45 minutes, range 20 to 60
      minutes; midazolam/flumazenil group: median 5 minutes, range 2 to 90 minutes).
      All patients in the midazolam/flumazenil group but 1 became resedated after
      flumazenil was discontinued. Four patients who had received etomidate exhibited
      myoclonus, which was pronounced and seizure-like in 1 case. CONCLUSION: Four
      sedative regimens (propofol, etomidate, midazolam, and midazolam/flumazenil) were
      uniformly effective in facilitating ED cardioversion in hemodynamically stable
      adults. Propofol was well tolerated and lacked the myoclonus, prolonged sedation,
      and resedation noted with the latter 3 respective groups. Larger studies are
      needed to generalize these conclusions.

PMID- 14634602
TI  - Propofol for procedural sedation in children in the emergency department.
AB  - STUDY OBJECTIVE: We determine the safety and efficacy of propofol sedation for
      painful procedures in the emergency department (ED). METHODS: A consecutive case
      series of propofol sedations for painful procedures in the ED of a tertiary care
      pediatric hospital from July 2000 to July 2002 was performed. A sedation protocol
      was followed. Propofol was administered in a bolus of 1 mg/kg, followed by
      additional doses of 0.5 mg/kg. Narcotics were administered 1 minute before
      propofol administration. Adverse events were documented, as were the sedation
      duration, recovery time from sedation, and total time in the ED. RESULTS: Three
      hundred ninety-three discrete sedation events with propofol were analyzed.
      Procedures consisted of the following: fracture reductions (94%), reduction of
      joint dislocations (4%), spica cast placement (2%), and ocular examination after
      an ocular burn (0.3%). The median propofol dose was 2.7 mg/kg. Ninety-two percent
      of patients had a transient (<or=2 minutes) decrease in systolic blood pressure
      without clinical signs of poor perfusion. Nineteen (5%) patients had hypoxia, 11
      (3%) patients required airway repositioning or jaw-thrust maneuvers, and 3 (0.8%)
      patients required bag-valve-mask ventilation. No patient required endotracheal
      intubation. CONCLUSION: Propofol sedation is efficacious and can be used safely
      in the ED setting under the guidance of a protocol. Transient cardiopulmonary
      depression occurs, which requires vigilant monitoring by highly skilled
      practitioners. Propofol is well suited for short, painful procedures in the ED
      setting.

PMID- 14634603
TI  - Propofol sedation by emergency physicians for elective pediatric outpatient
      procedures.
AB  - STUDY OBJECTIVE: We describe the efficacy of propofol sedation administered by
      pediatric emergency physicians to facilitate painful outpatient procedures.
      METHODS: By using a protocol for patients receiving propofol sedation in an
      emergency department-affiliated short-stay unit, a prospective, consecutive case
      series was performed from January to September 2000. Patients were prescheduled,
      underwent a medical evaluation, and met fasting requirements. A sedation team was
      present throughout the procedure. All patients received supplemental oxygen.
      Sedation depth and vital signs were monitored while propofol was manually
      titrated to the desired level of sedation. RESULTS: There were 291 separate
      sedation events in 87 patients. No patient had more than 1 sedation event per
      day. Median patient age was 6 years; 57% were male patients and 72% were oncology
      patients. Many children required more than 1 procedure per encounter. Most
      commonly performed procedures included lumbar puncture (43%), intrathecal
      chemotherapy administration (31%), bone marrow aspiration (19%), and bone biopsy
      (3%). Median total propofol dose was 3.5 mg/kg. Median systolic and diastolic
      blood pressures were lowered 22 mm Hg (range 0 to 65 mm Hg) and 21 mm Hg (range 0
      to 62 mm Hg), respectively. Partial airway obstruction requiring brief jaw-thrust
      maneuver was noted for 4% of patient sedations, whereas transient apnea requiring
      bag-valve-mask ventilation occurred in 1% of patient sedations. All procedures
      were successfully completed. Median procedure duration was 13 minutes, median
      sedation duration was 22 minutes, and median total time in the short stay unit
      was 40 minutes. CONCLUSION: Propofol sedation administered by emergency
      physicians safely facilitated short painful procedures in children under
      conditions studied, with rapid recovery.

PMID- 14634604
TI  - Propofol in emergency medicine: pushing the sedation frontier.

PMID- 14634605
TI  - FiGHTS: a preliminary screening tool for adolescent firearms-carrying.
AB  - STUDY OBJECTIVE: Adolescent firearms-carrying is a risk factor for serious injury
      and death. Clinical screening tools for firearms-carrying have not yet been
      developed. We present the development of a preliminary screening test for
      adolescent firearms-carrying based on the growing body of knowledge of firearms
      related risk factors. METHODS: A convenience sample of 15,000 high school
      students from the 1999 National Youth Risk Behavior Survey was analyzed for the
      purpose of model building. Known risk factors for firearms-carrying were
      candidates for 2 models predicting recent firearms-carrying. The "brief FiGHTS
      score" screening tool excluded terms related to sexual behavior, significant
      substance abuse, or criminal behavior (Fi=fighting, G=gender, H=hurt while
      fighting, T=threatened, S=smoker). An "extended FiGHTS score," which included 13
      items, was developed for more precise estimates. RESULTS: The brief FiGHTS score
      had a sensitivity of 82%, a specificity of 71%, and an area under the receiver
      operating characteristic (ROC) curve of 0.84. The extended FiGHTS score had an
      area under the ROC curve of 0.90. Both models performed well in a validation data
      set of 55,000 students. CONCLUSION: The brief and extended FiGHTS scores have
      high sensitivity and specificity for predicting firearms-carrying and may be
      appropriate for clinical testing.

PMID- 14634606
TI  - Screening for adolescent firearms-carrying: one more way to save a life.

PMID- 14634607
TI  - Drug-impaired driving: new resources in understanding the problem.

PMID- 14634609
TI  - A framework for classifying factors that contribute to error in the emergency
      department.
AB  - The Institute of Medicine report in 1999 spurred a national movement in patient
      safety and focused attention on medical error as a significant cause of
      preventable injury and death. Throughout the past decade, the medical community
      has gradually acknowledged the fallibility of medical science and imperfections
      of our health care organizations. Before significant progress can be made to
      improve safety in health care, we must better understand the sources of error.
      This article is presented as one step in the process of change. A framework for
      classifying factors that contributed to errors identified in the emergency
      department (ED) is presented. The framework is, in its most basic form, a
      comprehensive checklist of all the sources of error uncovered in the course of
      investigating hundreds of cases referred to Stroger Hospital's emergency medicine
      quality assurance committee throughout the past decade. It begins with a look at
      error in the ED and then looks beyond the ED to examine error in the context of
      the wider health care system. It incorporates ideas found in safety engineering,
      transportation safety, human factors engineering, and our own experience in an
      urban, public, teaching hospital ED.

PMID- 14634610
TI  - Emergency department crowding: consensus development of potential measures.
AB  - STUDY OBJECTIVE: We identify measures of emergency department (ED) and hospital
      workflow that would be of value in understanding, monitoring, and managing
      crowding. METHODS: A national group of 74 experts developed 113 potential
      measures using a conceptual model of ED crowding that segmented the measures into
      input, throughput, and output categories. Ten investigators then used group
      consensus methods to revise and consolidate them into a refined set of 30
      measures that were rated by all 74 experts, who used a magnitude estimation
      technique on a Web site. Each measure was compared with a standard to obtain
      numeric ratings for feasibility, affordability, early warning potential, long
      term planning potential, a summary rating of operational usefulness, and research
      potential. After review of the comprehensiveness of the resulting measures, 8
      additional measures were developed and also rated by all reviewers. RESULTS: The
      original set of 113 measures (46 input, 35 throughput, and 32 output) was reduced
      to 38 through the iterative revision and rating process (15 input, 9 throughput,
      and 14 output). Summary scores in each rating category showed significant
      variation in ratings among the various potential measures. For measures that
      address similar concepts, the priority ranking depended on the rating category
      chosen. CONCLUSION: The final 38 measures of ED and hospital workflow provide a
      useful pool from which EDs and policymakers can draw to improve their ability to
      understand and address the issue of ED crowding. These measures require rigorous
      testing for feasibility, reliability, and value.

PMID- 14634611
TI  - Antibiotic use for emergency department patients with acute diarrhea: Prescribing
      practices, patient expectations, and patient satisfaction.
AB  - STUDY OBJECTIVE: Physicians commonly prescribe antibiotics to meet patient
      expectations, even when antimicrobials are unnecessary. We evaluated factors
      emergency physicians consider in prescribing antibiotics to patients with
      diarrhea and examined patient expectations, physician-perceived patient
      expectations, and patient satisfaction. METHODS: Adults and children presenting
      with acute diarrhea to 1 of 10 academic emergency departments (EDs) were enrolled
      in this prospective observational cohort study. Adult patients and guardians of
      enrolled children were asked about treatment expectations before their physician
      encounter and about satisfaction with their medical care at discharge. Physicians
      were asked about factors influencing management decisions and their perceptions
      of patients' expectations. RESULTS: Of 104 patients enrolled, 25% received
      antibiotics. Physicians were more likely to prescribe antibiotics when features
      suggestive of bacterial enteritis were present (unadjusted odds ratio [OR] 2.5;
      95% confidence interval [CI] 1.1 to 3.9). Physicians were also more likely to
      prescribe antibiotics when they believed patients expected them (unadjusted OR
      2.3; 95% CI 1.1 to 4.4) but correctly identified such expectations in only 33% of
      instances. Satisfaction with care was reported by 100% of patients receiving
      antibiotics and 90% of those not receiving antibiotics (95% CI for difference of
      10%, 3% to 17%). CONCLUSION: Physicians in academic EDs prescribe antibiotics for
      acute diarrhea to about 1 patient in 4 and are more likely to do so if signs or
      symptoms compatible with bacterial enteritis are present. Physicians' assessments
      of patients' expectations for therapy were accurate in only 1 of 3 patients but
      were nevertheless associated with antibiotic prescription. Patient satisfaction
      was weakly associated with receipt of antibiotics.

PMID- 14634612
TI  - "You are commanded to appear": The subpoena and the emergency medicine resident.

PMID- 14634618
TI  - A decade of caspases.
AB  - Caspases are a family of cysteine proteases that play important roles in
      regulating apoptosis. A decade of research has generated a wealth of information
      on the signal transduction pathways mediated by caspases, the distinct functions
      of individual caspases and the mechanisms by which caspases mediate apoptosis and
      a variety of physiological and pathological processes.

PMID- 14634619
TI  - The inhibitors of apoptosis: there is more to life than Bcl2.
AB  - The inhibitor of apoptosis (IAP) genes constitute a highly conserved family found
      in organisms as diverse as insects and mammals. These genes encode proteins that
      directly bind and inhibit caspases, and thus play a critical role in deciding
      cell fate. The IAPs are in turn regulated by endogenous proteins (second
      mitochondrial activator of caspases and Omi) that are released from the
      mitochondria during apoptosis. Overexpression of the IAPs, particularly the X
      chromosome-linked IAP, has been shown to be protective in a variety of
      experimental animal models of human neurodegenerative diseases. Furthermore,
      overexpression of one or more of the IAPs in cancer cell lines and primary tumor
      samples appears to be a frequent event. IAP gene amplification and translocation
      events provide genetic evidence that further strengthens the case for classifying
      the IAPs as oncogenes. Therapeutic strategies that interfere with IAP expression
      or function are under investigation as an adjuvant to conventional chemotherapy-
      and radiation-based cancer therapy. This paper reviews the structure and function
      of the IAP family members and their inhibitors, and surveys the available
      evidence for IAP dysregulation in cancer.

PMID- 14634620
TI  - Survivin, versatile modulation of cell division and apoptosis in cancer.
AB  - Survivin is a member of the inhibitor of apoptosis (IAP) gene family that has
      attracted attention from several viewpoints of basic and translational research.
      Its cell cycle-regulated expression at mitosis and association with the mitotic
      apparatus have been of interest to cell biologists studying faithful segregation
      of sister chromatids and timely separation of daughter cells. Investigators
      interested in mechanisms of apoptosis have found survivin an evolving challenge:
      while survivin inhibits apoptosis in vitro and in vivo, this pathway may be more
      selective as compared to cytoprotection mediated by other IAPs. Finally, basic
      and translational researchers in cancer biology have converged on survivin as a
      pivotal cancer gene, not simply for its sharp expression in tumors and not in
      normal tissues, but also for the potential exploitation of this pathway in cancer
      diagnosis and therapy. The objective of the present contribution is to line up
      current evidence and emerging concepts on the multifaceted functions of survivin
      in cell death and cell division, and how this pathway is being pursued for novel
      cancer therapeutic strategies.

PMID- 14634621
TI  - The Bcl-2 family: roles in cell survival and oncogenesis.
AB  - Apoptosis, the cell-suicide programme executed by caspases, is critical for
      maintaining tissue homeostasis, and impaired apoptosis is now recognized to be a
      key step in tumorigenesis. Whether a cell should live or die is largely
      determined by the Bcl-2 family of anti- and proapoptotic regulators. These
      proteins respond to cues from various forms of intracellular stress, such as DNA
      damage or cytokine deprivation, and interact with opposing family members to
      determine whether or not the caspase proteolytic cascade should be unleashed.
      This review summarizes current views of how these proteins sense stress, interact
      with their relatives, perturb organelles such as the mitochondrion and
      endoplasmic reticulum and govern pathways to caspase activation. It briefly
      explores how family members influence cell-cycle entry and outlines the evidence
      for their involvement in tumour development, both as oncoproteins and tumour
      suppressors. Finally, it discusses the promise of novel anticancer therapeutics
      that target these vital regulators.

PMID- 14634622
TI  - Regulation of apoptosis by endoplasmic reticulum pathways.
AB  - Apoptotic programmed cell death pathways are activated by a diverse array of cell
      extrinsic and intrinsic signals, most of which are ultimately coupled to the
      activation of effector caspases. In many instances, this involves an obligate
      propagation through mitochondria, causing egress of critical proapoptotic
      regulators to the cytosol. Central to the regulation of the mitochondrial
      checkpoint is a complex three-way interplay between members of the BCL-2 family,
      which are comprised of an antiapoptotic subgroup including BCL-2 itself, and the
      proapoptotic BAX,BAK and BH3-domain-only subgroups. Constituents of all three of
      these BCL-2 classes, however, also converge on the endoplasmic reticulum (ER), an
      organelle whose critical contributions to apoptosis is only now becoming
      apparent. In addition to propagating death-inducing stress signals itself, the ER
      also contributes in a fundamental way to Fas-mediated apoptosis and to p53
      dependent pathways resulting from DNA damage and oncogene expression.
      Mobilization of ER calcium stores can initiate the activation of cytoplasmic
      death pathways as well as sensitize mitochondria to direct proapoptotic stimuli.
      Additionally, the existence of BCL-2-regulated initiator procaspase activation
      complexes at the ER membrane has also been described. Here, we review the
      potential underlying mechanisms involved in these events and discuss pathways for
      ER-mitochondrial crosstalk pertinent to a number of cell death stimuli.

PMID- 14634623
TI  - Calcium and apoptosis: facts and hypotheses.
AB  - Although longstanding experimental evidence has associated alterations of calcium
      homeostasis to cell death, only in the past few years the role of calcium in the
      signaling of apoptosis has been extensively investigated. In this review, we will
      summarize the current knowledge, focusing on (i) the effect of the proteins of
      the Bcl-2 family on ER Ca2+ levels, (ii) the action of the proteolytic enzymes of
      apoptosis on the Ca2+ signaling machinery, (iii) the ensuing alterations on the
      signaling patterns of extracellular stimuli, and (iv) the intracellular targets
      of 'apoptotic' Ca2+ signals, with special emphasis on the mitochondria and
      cytosolic Ca2+-dependent enzymes.

PMID- 14634624
TI  - TRAIL and apoptosis induction by TNF-family death receptors.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand
      (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family of ligands
      capable of initiating apoptosis through engagement of its death receptors. TRAIL
      selectively induces apoptosis of a variety of tumor cells and transformed cells,
      but not most normal cells, and therefore has garnered intense interest as a
      promising agent for cancer therapy. TRAIL is expressed on different cells of the
      immune system and plays a role in both T-cell- and natural killer cell-mediated
      tumor surveillance and suppression of suppressing tumor metastasis. Some mismatch
      repair-deficient tumors evade TRAIL-induced apoptosis and acquire TRAIL
      resistance through different mechanisms. Death receptors, members of the TNF
      receptor family, signal apoptosis independently of the p53 tumor-suppressor gene.
      TRAIL treatment in combination with chemo- or radiotherapy enhances TRAIL
      sensitivity or reverses TRAIL resistance by regulating the downstream effectors.
      Efforts to identify agents that activate death receptors or block specific
      effectors may improve therapeutic design. In this review, we summarize recent
      insights into the apoptosis-signaling pathways stimulated by TRAIL, present our
      current understanding of the physiological role of this ligand and the potential
      of its application for cancer therapy and prevention.

PMID- 14634625
TI  - The death effector domain protein family.
AB  - Apoptosis signaling is regulated and executed by specialized proteins that often
      carry protein/protein interaction domains. One of these domains is the death
      effector domain (DED) that is predominantly found in components of the death
      inducing signaling complex, which forms at the members of the death receptor
      family following their ligation. Both proapoptotic- and antiapoptotic-DED
      containing proteins have been identified, which makes these proteins exquisitely
      suited to the regulation of apoptosis. Aside from their pivotal role in the
      control of the apoptotic program, DED-containing proteins have recently been
      demonstrated to exert their influence on other cellular processes as well,
      including cell proliferation. These data highlight the multiple roles for the
      members of this family, suggesting that they are suited to control both life and
      death decisions of cells. Additionally, because they can act proapoptotically,
      antiapoptotically, or in the regulation of the cell cycle, this family of
      proteins may be excellent candidates for cancer therapy targets. Oncogene (2003)
      22, 8634-8644. doi:10.1038/sj.onc.1207103

PMID- 14634626
TI  - Small RNAs come of age.

PMID- 14634627
TI  - Announcing the worldwide Protein Data Bank.

PMID- 14634628
TI  - Tom40: more than just a channel.

PMID- 14634629
TI  - Histone H1.2 as a trigger for apoptosis.

PMID- 14634631
TI  - Fingering nucleic acids: the RNA did it.

PMID- 14634633
TI  - Human cloning: can it be made safe?
AB  - There are continued claims of attempts to clone humans using nuclear transfer,
      despite the serious problems that have been encountered in cloning other mammals.
      It is known that epigenetic and genetic mechanisms are involved in clone failure,
      but we still do not know exactly how. Human reproductive cloning is unethical,
      but the production of cells from cloned embryos could offer many potential
      benefits. So, can human cloning be made safe?

PMID- 14634634
TI  - The origin of new genes: glimpses from the young and old.
AB  - Genome data have revealed great variation in the numbers of genes in different
      organisms, which indicates that there is a fundamental process of genome
      evolution: the origin of new genes. However, there has been little opportunity to
      explore how genes with new functions originate and evolve. The study of ancient
      genes has highlighted the antiquity and general importance of some mechanisms of
      gene origination, and recent observations of young genes at early stages in their
      evolution have unveiled unexpected molecular and evolutionary processes.

PMID- 14634635
TI  - The genetic and molecular basis of congenital eye defects.
AB  - The mature eye is a complex organ that develops through a highly organized
      process during embryogenesis. Alterations in its genetic programming can lead to
      severe disorders that become apparent at birth or shortly afterwards; for
      example, one-half of the cases of blindness in children have a genetic cause.
      This review outlines the genetic basis of eye development, as determined by
      mutation analysis in patients and in model organisms. A better understanding of
      how this intricate organ develops at the genetic and cellular level is central to
      our understanding of the pathologies that afflict it.

PMID- 14634636
TI  - Genes in new environments: genetics and evolution in biological control.
AB  - The availability of new genetic technologies has positioned the field of
      biological control as a test bed for theories in evolutionary biology and for
      understanding practical aspects of the release of genetically manipulated
      material. Purposeful introductions of pathogens, parasites, predators and
      herbivores, when considered as replicated semi-natural field experiments, show
      the unpredictable nature of biological colonization. The characteristics of
      organisms and their environments that determine this variation in the
      establishment and success of biological control can now be explored using genetic
      tools. Lessons from studies of classical biological control can help inform
      researchers and policy makers about the risks that are associated with the
      release of genetically modified organisms, particularly with respect to long-term
      evolutionary changes.

PMID- 14634637
TI  - DNA markers reveal the complexity of livestock domestication.
AB  - A series of recent genetic studies has revealed the remarkably complex picture of
      domestication in both New World and Old World livestock. By comparing
      mitochondrial and nuclear DNA sequences of modern breeds with their potential
      wild and domestic ancestors, we have gained new insights into the timing and
      location of domestication events that produced the farm animals of today. The
      real surprise has been the high number of domestication events and the diverse
      locations in which they took place - factors which could radically change our
      approach to conserving livestock biodiversity resources in the future.

PMID- 14634639
TI  - Clues to catastrophic telomere loss in mammals from yeast telomere rapid
      deletion.
AB  - Catastrophic losses of telomeric sequences have recently been described during
      apoptosis, senescence and tumorigenesis in murine and human cells, in ataxia
      telangiectasia patients and in immortalized cells in which telomerase is
      inactive. A mechanism that underlies a single-step non-reciprocal telomere
      deletion called telomere rapid deletion in Saccharomyces cerevisiae might provide
      clues for future studies of catastrophic telomere loss in higher eukaryotes.

PMID- 14634641
TI  - Ultradispersity of diamond at the nanoscale.
AB  - Nanometre-sized diamond has been found in meteorites, protoplanetary nebulae and
      interstellar dusts, as well as in residues of detonation and in diamond films.
      Remarkably, the size distribution of diamond nanoparticles seems to be peaked
      around 2-5 nm, and to be largely independent of preparation conditions. We have
      carried out ab initio calculations of the stability of nanodiamond as a function
      of surface hydrogen coverage and of size. We have found that at about 3 nm, and
      for a broad range of pressures and temperatures, particles with bare,
      reconstructed surfaces become thermodynamically more stable than those with
      hydrogenated surfaces, thus preventing the formation of larger grains. Our
      findings provide an explanation of the size distribution of extraterrestrial and
      of terrestrial nanodiamond found in ultradispersed and ultracrystalline diamond
      films. They also provide an atomistic structural model of these films, based on
      the topology and structure of 2-3-nm dimond clusters consisting of a diamond core
      surrounded by a fullerene-like carbon network.

PMID- 14634640
TI  - Complex and oriented ZnO nanostructures.
AB  - Extended and oriented nanostructures are desirable for many applications, but
      direct fabrication of complex nanostructures with controlled crystalline
      morphology, orientation and surface architectures remains a significant
      challenge. Here we report a low-temperature, environmentally benign, solution
      based approach for the preparation of complex and oriented ZnO nanostructures,
      and the systematic modification of their crystal morphology. Using controlled
      seeded growth and citrate anions that selectively adsorb on ZnO basal planes as
      the structure-directing agent, we prepared large arrays of oriented ZnO nanorods
      with controlled aspect ratios, complex film morphologies made of oriented
      nanocolumns and nanoplates (remarkably similar to biomineral structures in red
      abalone shells) and complex bilayers showing in situ column-to-rod morphological
      transitions. The advantages of some of these ZnO structures for photocatalytic
      decompositions of volatile organic compounds were demonstrated. The novel ZnO
      nanostructures are expected to have great potential for sensing, catalysis,
      optical emission, piezoelectric transduction, and actuations.

PMID- 14634638
TI  - The nature and identification of quantitative trait loci: a community's view.
AB  - This white paper by eighty members of the Complex Trait Consortium presents a
      community's view on the approaches and statistical analyses that are needed for
      the identification of genetic loci that determine quantitative traits.
      Quantitative trait loci (QTLs) can be identified in several ways, but is there a
      definitive test of whether a candidate locus actually corresponds to a specific
      QTL?

PMID- 14634642
TI  - An encapsulated helical one-dimensional cobalt iodide nanostructure.
AB  - Single-walled carbon nanotubes (SWNTs) can be used as templates for the growth of
      low-dimensional inorganic materials whose structures and properties often differ
      greatly from those of the bulk. Here we describe the detailed crystallography of
      an entire helical one-dimensional cobalt diiodide nanostructure encapsulated
      within a SWNT. This material has an unprecedented twisted double tetrahedral
      chain structure arising from a rotation of Co(2)I(4) units along its length. The
      complete nanostructure comprises two distinct regions with oppositely handed
      helices separated by a short disordered region. The encapsulating SWNT shows a
      commensurate ovoid distortion reflecting an unexpectedly strong interaction
      between the nanostructure and the SWNT.

PMID- 14634643
TI  - Cationic comb-type copolymers for DNA analysis.
AB  - Genetic diagnoses, such as single nucleotide polymorphism (SNP) typing, allow
      elucidation of gene-based physiological differences, such as susceptibility to
      diseases and response to drugs, among individuals. Many detection technologies,
      including allele-specific hybridization, allele-specific primer extension and
      oligonucleotide ligation, are being used to discriminate SNP alleles. These
      methods still have many unsolved practical issues. In general they require
      adequate and specific hybridizations of primer or probe DNAs with target DNAs.
      This frequently needs optimization of the probe/primer structures and operating
      conditions. In nature, highly homology-sensitive hybridization is assisted by a
      nucleic acid chaperone that reduces the energy barrier associated with breakage
      and reassociation of nucleic base pairs. Here we report a simple, quick, precise
      but enzyme-free method for SNP analysis. The method uses cationic comb-type
      copolymers (CCCs) producing high nucleic acid chaperone activities. A single-base
      mismatch in 20-mer DNA can be detected within a few minutes at ambient
      temperatures (25-37 degrees C). Even without careful optimization processes, the
      method has the sensitivity to detect the mismatches causing subtle changes (Delta
      T(m) equals approximately 1 degree C) in duplex thermal stability. CCCs may have
      various bioanalytical applications where precise hybridization of nucleic acids
      is needed.

PMID- 14634644
TI  - A novel anionic surfactant templating route for synthesizing mesoporous silica
      with unique structure.
AB  - Anionic surfactants are used in greater volume than any other surfactants because
      of their highly potent detergency and low cost of manufacture. However, they have
      not been used as templates for synthesizing mesoporous silica. Here we show a
      templating route for preparing mesoporous silicas based on self-assembly of
      anionic surfactants and inorganic precursors. We use aminosilane or quaternized
      aminosilane as co-structure-directing agent (CSDA), which is different from
      previous pathways. The alkoxysilane site of CSDA is co-condensed with inorganic
      precursors; the ammonium site of CSDA, attached to silicon atoms incorporated
      into the wall, electrostatically interacts with the anionic surfactants to
      produce well-ordered anionic-surfactant-templated mesoporous silicas (AMS). These
      have new structures with periodic modulations as well as two-dimensional
      hexagonal and lamellar phases. The periodic modulations may be caused by the
      coexistence of micelles that differ in size or curvature, possibly owing to local
      chirality. These mesoporous silicas provide a new family of mesoporous materials
      as well as shedding light on the structural behaviour of anionic surfactants.

PMID- 14634645
TI  - Local gene knockdown in the brain using viral-mediated RNA interference.
AB  - Conditional mutant techniques that allow spatial and temporal control over gene
      expression can be used to create mice with restricted genetic modifications.
      These mice serve as powerful disease models in which gene function in adult
      tissues can be specifically dissected. Current strategies for conditional genetic
      manipulation are inefficient, however, and often lack sufficient spatial control.
      Here we use viral-mediated RNA interference (RNAi) to generate a specific
      knockdown of Th, the gene encoding the dopamine synthesis enzyme tyrosine
      hydroxylase, within midbrain neurons of adult mice. This localized gene knockdown
      resulted in behavioral changes, including a motor performance deficit and reduced
      response to a psychostimulant. These results underscore the potential of using
      viral-mediated RNAi for the rapid production and testing of new genetic disease
      models. Similar strategies may be used in other model species, and may ultimately
      find applications in human gene therapy.

PMID- 14634646
TI  - Vascular endothelial growth factor C is required for sprouting of the first
      lymphatic vessels from embryonic veins.
AB  - Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis
      and fat absorption. Defects in lymphatic vessel formation or function cause
      lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C)
      is required for the initial steps in lymphatic development. In Vegfc-/- mice,
      endothelial cells commit to the lymphatic lineage but do not sprout to form lymph
      vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating
      VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal
      death due to fluid accumulation in tissues, and Vegfc+/- mice developed cutaneous
      lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the
      paracrine factor essential for lymphangiogenesis, and show that both Vegfc
      alleles are required for normal lymphatic development.

PMID- 14634647
TI  - Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral
      muscular dystrophy.
AB  - The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD1,
      OMIM 158900) is caused by contraction of the D4Z4 repeat array on 4qter. We show
      that this contraction causes marked hypomethylation of the contracted D4Z4 allele
      in individuals with FSHD1. Individuals with phenotypic FSHD1, who are clinically
      identical to FSHD1 but have an unaltered D4Z4, also have hypomethylation of D4Z4.
      These results strongly suggest that hypomethylation of D4Z4 is a key event in the
      cascade of epigenetic events causing FSHD1.

PMID- 14634648
TI  - Gene-culture coevolution between cattle milk protein genes and human lactase
      genes.
AB  - Milk from domestic cows has been a valuable food source for over 8,000 years,
      especially in lactose-tolerant human societies that exploit dairy breeds. We
      studied geographic patterns of variation in genes encoding the six most important
      milk proteins in 70 native European cattle breeds. We found substantial
      geographic coincidence between high diversity in cattle milk genes, locations of
      the European Neolithic cattle farming sites (>5,000 years ago) and present-day
      lactose tolerance in Europeans. This suggests a gene-culture coevolution between
      cattle and humans.

PMID- 14634650
TI  - Spike timing of dendrite-targeting bistratified cells during hippocampal network
      oscillations in vivo.
AB  - Behavior-contingent network oscillations bring about transient, functionally
      coherent neuronal assemblies in the cerebral cortex, including the hippocampus.
      Inhibitory input on and close to the soma is believed to phase intrinsic
      oscillations and output of pyramidal cells, but the function of GABA release to
      pyramidal cell dendrites remains unknown. We recorded the oscillation-locked
      spike timing of identified bistratified interneurons in rats. These cells mainly
      innervated small dendritic shafts of pyramidal cells co-aligned with the
      glutamatergic Schaffer collateral/commissural input. During theta oscillations,
      bistratified cells fired at a phase when, on average, pyramidal cell dendrites
      are most hyperpolarized. Interneurons targeting the perisomatic domain discharge
      at an earlier phase. During sharp wave-associated ripples, bistratified cells
      fired with high frequency and in-phase with basket cells, on average 1-2 ms after
      the discharges in pyramidal cell somata and dendrites. Our results indicate that
      bistratified cells rhythmically modulate glutamatergic input to the dendrites of
      pyramidal cells to actively promote the precise input/output transformation
      during network oscillations.

PMID- 14634649
TI  - Mutations in the polyglutamine binding protein 1 gene cause X-linked mental
      retardation.
AB  - We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX)
      and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical
      features in affected males include mental retardation, microcephaly, short
      stature, spastic paraplegia and midline defects. PQBP1 has previously been
      implicated in the pathogenesis of polyglutamine expansion diseases. Our findings
      link this gene to XLMR and shed more light on the pathogenesis of this common
      disorder.

PMID- 14634651
TI  - Scanning the social brain.

PMID- 14634652
TI  - Thinking about interracial interactions.

PMID- 14634653
TI  - Sensory-motor control: a long-awaited behavioral correlate of presynaptic
      inhibition.

PMID- 14634654
TI  - Doublecortin finds its place.

PMID- 14634655
TI  - Specifying motor neurons: up and down and back to front.

PMID- 14634656
TI  - Folding the cortex.

PMID- 14634657
TI  - Inference of hand movements from local field potentials in monkey motor cortex.
AB  - The spiking of neuronal populations in motor cortex provides accurate information
      about movement parameters. Here we show that hand movement target and velocity
      can be inferred from multiple local field potentials (LFPs) in single trials
      approximately as efficiently as from multiple single-unit activity (SUA) recorded
      from the same electrodes. Our results indicate that LFPs can be used as an
      additional signal for decoding brain activity, particularly for new
      neuroprosthetic applications.

PMID- 14634662
TI  - RGS16 inhibits signalling through the G alpha 13-Rho axis.
AB  - G alpha 13 stimulates the guanine nucleotide exchange factors (GEFs) for Rho,
      such as p115Rho-GEF. Activated Rho induces numerous cellular responses, including
      actin polymerization, serum response element (SRE)-dependent gene transcription
      and transformation. p115Rho-GEF contains a Regulator of G protein Signalling
      domain (RGS box) that confers GTPase activating protein (GAP) activity towards G
      alpha 12 and G alpha 13 (ref. 3). In contrast, classical RGS proteins (such as
      RGS16 and RGS4) exhibit RGS domain-dependent GAP activity on G alpha i and G
      alpha q, but not G alpha 12 or G alpha 13 (ref 4). Here, we show that RGS16
      inhibits G alpha 13-mediated, RhoA-dependent reversal of stellation and SRE
      activation. The RGS16 amino terminus binds G alpha 13 directly, resulting in
      translocation of G alpha 13 to detergent-resistant membranes (DRMs) and reduced
      p115Rho-GEF binding. RGS4 does not bind G alpha 13 or attenuate G alpha 13
      dependent responses, and neither RGS16 nor RGS4 affects G alpha 12-mediated
      signalling. These results elucidate a new mechanism whereby a classical RGS
      protein regulates G alpha 13-mediated signal transduction independently of the
      RGS box.

PMID- 14634663
TI  - Securin and B-cyclin/CDK are the only essential targets of the APC.
AB  - The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin
      ligase that controls passage through the cell cycle by targeting many proteins
      for proteolysis. The complex is composed of at least thirteen core subunits,
      eight of which are essential, and two activating subunits, Cdc20 (essential) and
      Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are
      sufficient to explain the essential nature of the complex. Here, we show that
      each of the eight normally essential APC subunits is rendered non-essential
      ('bypass-suppressed') by the simultaneous removal/inhibition of the APC
      substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the
      APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as
      cells cycle. This suggests that in the absence of B-type cyclin destruction,
      oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback
      loops necessary for the bi-stable nature of Clb/CDK activity. These results
      strongly suggest that securin and B-type cyclin/CDK activity are the only
      obligatory targets of the APC in Saccharomyces cerevisiae.

PMID- 14634664
TI  - Alternate fast and slow stepping of a heterodimeric kinesin molecule.
AB  - A conventional kinesin molecule travels continuously along a microtubule in
      discrete 8-nm steps. This processive movement is generally explained by models in
      which the two identical heads of a kinesin move in a 'hand-over-hand' manner.
      Here, we show that a single heterodimeric kinesin molecule (in which one of the
      two heads is mutated in a nucleotide-binding site) exhibits fast and slow (with
      the dwell time at least 10 times longer than that of the fast step) 8-nm steps
      alternately, presumably corresponding to the displacement by the wild-type and
      mutant heads, respectively. Our results provide the first direct evidence for
      models in which the roles of the two heads alternate every 8-nm step.

PMID- 14634665
TI  - Mitochondrial translocation of cofilin is an early step in apoptosis induction.
AB  - Increasing evidence suggests that movement of key proteins in or out of
      mitochondria during apoptosis is essential for the regulation of apoptosis. Here,
      we report identification of the actin-binding protein cofilin by a proteomic
      approach, as such a factor translocated from cytosol into mitochondria after
      induction of apoptosis. We found that after induction of apoptosis, cofilin was
      translocated to mitochondria before release of cytochrome c. Reduction of cofilin
      protein levels with small-interfering RNA (siRNA) resulted in inhibition of both
      cytochrome c release and apoptosis. Only dephosphorylated cofilin was
      translocated to mitochondria, and the cofilin S3D mutant, which mimicks the
      phosphorylated form, suppressed mitochondrial translocation and apoptosis.
      Translocation was achieved through exposure of an amino-terminal mitochondrial
      targeting signal in combination with carboxy-terminal sequences. When correctly
      targeted to mitochondria, cofilin induced massive apoptosis. The apoptosis
      inducing ability of cofilin, but not its mitochondrial localization, was
      dependent on the functional actin-binding domain. Thus, domains involved in
      mitochondrial targeting and actin binding are indispensable for its pro-apoptotic
      function. Our data suggest that cofilin has an important function during the
      initiation phase of apoptosis.

PMID- 14634666
TI  - Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock.
AB  - Sensing the osmolarity of the environment is a critical response for all
      organisms. Whereas bacteria will migrate away from high osmotic conditions, most
      eukaryotic cells are not motile and use adaptive metabolic responses for
      survival. The p38 MAPK pathway is a crucial mediator of survival during cellular
      stress. We have discovered a novel scaffold protein that binds to actin, the
      GTPase Rac, and the upstream kinases MEKK3 and MKK3 in the p38 MAPK phospho-relay
      module. RNA interference (RNAi) demonstrates that MEKK3 and the scaffold protein
      are required for p38 activation in response to sorbitol-induced hyperosmolarity.
      FRET identifies a cytoplasmic complex of the MEKK3 scaffold protein that is
      recruited to dynamic actin structures in response to sorbitol treatment. Through
      its ability to bind actin, relocalize to Rac-containing membrane ruffles and its
      obligate requirement for p38 activation in response to sorbitol, we have termed
      this protein osmosensing scaffold for MEKK3 (OSM). The Rac-OSM-MEKK3-MKK3 complex
      is the mammalian counterpart of the CDC42-STE50-STE11-Pbs2 complex in
      Saccharomyces cerevisiae that is required for the regulation of p38 activity.

PMID- 14634667
TI  - A new sperm-specific Na+/H+ exchanger required for sperm motility and fertility.
AB  - It has long been speculated that intracellular pH is a critical regulator of both
      invertebrate and vertebrate sperm motility, and sodium-hydrogen exchange has been
      suggested as a mediator of such pH(i) regulation in various instances. Two sodium
      hydrogen exchangers (NHE1 and NHE5) are expressed in spermatozoa. However,
      elimination of the NHE1 gene fails to cause infertility, suggesting that normal
      sperm function is maintained in NHE1-null animals. Here, we used a functionally
      unbiased signal peptide trap screen to identify a novel sperm-specific NHE. The
      NHE contains 14 predicted transmembrane segments, including a potential voltage
      sensor and a consensus cyclic nucleotide-binding motif. Testis histology, sperm
      numbers and morphology were normal, but NHE-null males were completely infertile
      with severely diminished sperm motility. The addition of ammonium chloride, which
      elevates intracellular pH, partially rescued the motility and fertility defects.
      Surprisingly, cyclic AMP analogues almost completely rescued the motility and
      infertility phenotypes. The existence of this new sperm NHE provides an
      attractive contraceptive target, given its cell-specific expression and absolute
      requirement for fertility.

PMID- 14634668
TI  - Design of multivalent complexes using the barnase*barstar module.
AB  - The ribonuclease barnase (12 kDa) and its inhibitor barstar (10 kDa) form a very
      tight complex in which all N and C termini are accessible for fusion. Here we
      exploit this system to create modular targeting molecules based on antibody scFv
      fragment fusions to barnase, to two barnase molecules in series and to barstar.
      We describe the construction, production and purification of defined dimeric and
      trimeric complexes. Immobilized barnase fusions are used to capture barstar
      fusions from crude extracts to yield homogeneous, heterodimeric fusion proteins.
      These proteins are stable, soluble and resistant to proteolysis. Using fusions
      with anti-p185(HER2-ECD) 4D5 scFv, we show that the anticipated gain in avidity
      from monomer to dimer to trimer is obtained and that favorable tumor targeting
      properties are achieved. Many permutations of engineered multispecific fusion
      proteins become accessible with this technology of quasi-covalent heterodimers.

PMID- 14634669
TI  - Synaptotagmin I is necessary for compensatory synaptic vesicle endocytosis in
      vivo.
AB  - Neurotransmission requires a balance of synaptic vesicle exocytosis and
      endocytosis. Synaptotagmin I (Syt I) is widely regarded as the primary calcium
      sensor for synaptic vesicle exocytosis. Previous biochemical data suggest that
      Syt I may also function during synaptic vesicle endocytosis; however,
      ultrastructural analyses at synapses with impaired Syt I function have provided
      an indirect and conflicting view of the role of Syt I during synaptic vesicle
      endocytosis. Until now it has not been possible experimentally to separate the
      exocytic and endocytic functions of Syt I in vivo. Here, we test directly the
      role of Syt I during endocytosis in vivo. We use quantitative live imaging of a
      pH-sensitive green fluorescent protein fused to a synaptic vesicle protein
      (synapto-pHluorin) to measure the kinetics of endocytosis in sytI-null
      Drosophila. We then combine live imaging of the synapto-pHluorins with
      photoinactivation of Syt I, through fluorescein-assisted light inactivation,
      after normal Syt I-mediated vesicle exocytosis. By inactivating Syt I only during
      endocytosis, we demonstrate that Syt I is necessary for the endocytosis of
      synaptic vesicles that have undergone exocytosis using a functional Syt I
      protein.

PMID- 14634670
TI  - Backtracking by single RNA polymerase molecules observed at near-base-pair
      resolution.
AB  - Escherichia coli RNA polymerase (RNAP) synthesizes RNA with remarkable fidelity
      in vivo. Its low error rate may be achieved by means of a 'proofreading'
      mechanism comprised of two sequential events. The first event (backtracking)
      involves a transcriptionally upstream motion of RNAP through several base pairs,
      which carries the 3' end of the nascent RNA transcript away from the enzyme
      active site. The second event (endonucleolytic cleavage) occurs after a variable
      delay and results in the scission and release of the most recently incorporated
      ribonucleotides, freeing up the active site. Here, by combining ultrastable
      optical trapping apparatus with a novel two-bead assay to monitor transcriptional
      elongation with near-base-pair precision, we observed backtracking and recovery
      by single molecules of RNAP. Backtracking events ( approximately 5 bp) occurred
      infrequently at locations throughout the DNA template and were associated with
      pauses lasting 20 s to >30 min. Inosine triphosphate increased the frequency of
      backtracking pauses, whereas the accessory proteins GreA and GreB, which
      stimulate the cleavage of nascent RNA, decreased the duration of such pauses.

PMID- 14634671
TI  - Impact of localized badger culling on tuberculosis incidence in British cattle.
AB  - Pathogens that are transmitted between wildlife, livestock and humans present
      major challenges for the protection of human and animal health, the economic
      sustainability of agriculture, and the conservation of wildlife. Mycobacterium
      bovis, the aetiological agent of bovine tuberculosis (TB), is one such pathogen.
      The incidence of TB in cattle has increased substantially in parts of Great
      Britain in the past two decades, adversely affecting the livelihoods of cattle
      farmers and potentially increasing the risks of human exposure. The control of
      bovine TB in Great Britain is complicated by the involvement of wildlife,
      particularly badgers (Meles meles), which appear to sustain endemic infection and
      can transmit TB to cattle. Between 1975 and 1997 over 20,000 badgers were culled
      as part of British TB control policy, generating conflict between conservation
      and farming interest groups. Here we present results from a large-scale field
      trial that indicate that localized badger culling not only fails to control but
      also seems to increase TB incidence in cattle.

PMID- 14634672
TI  - Ecology: badger cull culled.

PMID- 14634673
TI  - Intentional weight loss and incidence of obesity-related cancers: the Iowa
      Women's Health Study.
AB  - OBJECTIVE: To examine the association of voluntary vs involuntary weight loss
      with incidence of cancer in older women. DESIGN: Prospective cohort study from
      1993 to 2000, with cancer incidence identified through record linkage to a cancer
      registry. SUBJECTS: A total of 21,707 postmenopausal women initially free of
      cancer. MEASUREMENTS: Women completed a questionnaire about intentional and
      unintentional weight loss episodes of > or =20 pounds during adulthood. RESULTS:
      Compared with women who never had any > or =20 pounds weight loss episode, women
      who ever experienced intentional weight loss > or =20 pounds but no unintentional
      weight loss had incidence rates lower by 11% for any cancer (RR=0.89, 95% CI 0.79
      1.00), by 19% for breast cancer (RR=0.81, 95% CI 0.66-1.00), by 9% for colon
      cancer (RR=0.91, 95% CI 0.66-1.24), by 4% for endometrial cancer (RR=0.96, 95% CI
      0.61-1.52), and by 14% for all obesity-related cancer (RR=0.86, 95% CI 0.74-1.01)
      after adjusting for age, body mass index, waist-to-hip ratio, physical activity,
      education, marital status, smoking status, pack-years of cigarettes, current
      estrogen use, alcohol use, parity, and multivitamin use. Furthermore, although
      overweight women were at increased risk of several cancers, women who experienced
      intentional weight loss episodes of 20 or more pounds and were not currently
      overweight were observed to have an incidence of cancer similar to nonoverweight
      women who never lost weight. Unintentional weight loss episodes were not
      associated with decreased cancer risk. CONCLUSIONS: These findings suggest that
      intentional weight loss might reduce risk of obesity-related cancers.

PMID- 14634674
TI  - Diurnal PaCO2 tension in obese women: relationship with sleep disordered
      breathing.
AB  - OBJECTIVE: Several obese subjects show a wide array of respiratory disturbances
      during sleep due to an increased upper-airway resistance. The aim of the present
      study was to evaluate diurnal PaCO(2) tension in nonsmoking obese women and the
      possible relationship of this parameter with the presence of sleep disordered
      breathing (SDB). DESIGN: Cross-sectional study of PaCO(2) tension in obese women.
      PATIENTS AND METHODS: A total of 91 nonsmoking obese women (BMI > or =30 kg/m(2),
      aged 42.8+/-15.7 y) were recruited and evaluated for general and anthropometric
      parameters, respiratory function, sleep-related symptoms, and sleep disorders of
      breathing. RESULTS: A total of 10 subjects (10.9%) had diurnal hypercapnia
      (PaCO(2)> or =43 mmHg). Age, BMI, neck circumference, apnoea/hypopnoea index, and
      nocturnal desaturation (expressed as TST(SaO(2<90%)); TST(SaO(2<90%))=percentage
      of total sleep time with oxyhaemoglobin saturation <90%) were significantly
      higher in obese patients with diurnal hypercapnia, compared to normocapnic women.
      Moreover, hypercapnic patients had reduced forced expiratory volume in 1 s
      compared to normocapnic individuals. By using multiple regression analysis, the
      best fitting model (r=0.62, P<0.001) for predicting diurnal PaCO(2) tension in
      the study population showed that 24.23% of the variance may be explained by
      TST(SaO(2<90%)), according to the equation: PaCO(2)=0.09 age+0.07
      TST(SaO(2<90%))+33.00. CONCLUSIONS: This study suggests that severity of SDB is
      the most important factor in determining diurnal PaCO(2) tension in apparently
      healthy nonsmoking obese women.

PMID- 14634675
TI  - Obesity and blood pressure--results from the examination of 2365 schoolchildren
      in Germany.
AB  - OBJECTIVES: To investigate the relationship between different indices of body fat
      and blood pressure in children and adolescents. DESIGN: Cross-sectional cohort
      study along with regular public health service examinations in school classes
      two, five and nine. PARTICIPANTS: A total of 2365 healthy schoolchildren aged 8
      16 y. MEASUREMENTS: Body mass index (BMI), skinfolds, waist-hip ratio, body fat
      determined by bioelectric impedance analysis and blood pressure. RESULTS: In
      comparison with recently published normative data, a significant increase of
      obesity was found. There is a higher prevalence of obesity in children with lower
      education. A positive association between body fat and hypertension was observed
      in children aged above 10 y. The BMI had the strongest association with blood
      pressure among the indices of body fat considered here. CONCLUSION: Obesity is an
      increasing problem even among schoolchildren. This observation should be treated
      seriously as the relationship of body fat to cardiovascular risk is detectable
      already at a young age. Attention should be paid to the dependence of obesity on
      the level of education. The analysis suggests that BMI should be the preferred
      index to assess body fat. International Journal of Obesity (2003) 27, 1459-1464.
      doi:10.1038/sj.ijo.0802462

PMID- 14634676
TI  - Public perceptions of the causes and prevention of obesity among primary school
      children.
AB  - OBJECTIVE: To investigate lay perceptions of the causes and prevention of obesity
      among primary school children. DESIGN: A cross-sectional survey of randomly
      selected sample of adults in a shopping centre. SUBJECTS: 315 adults in
      Melbourne, Australia. MEASUREMENTS: Subjects completed a self-completion
      questionnaire, in which they rated the importance of 25 possible causes of
      obesity and the importance of 13 preventive measures on four-point scales: not
      important; quite important; very important; extremely important. Demographic
      information about the respondents' age, sex, marital status, education level and
      parental status was also collected. RESULTS: The most important reported causes
      of childhood obesity were related to overconsumption of unhealthy food, parental
      responsibility, modern technology and the mass media. The most popular prevention
      activities were associated with specific actions aimed at children. Principal
      components analysis of the causes data revealed eight factors, provisionally
      named: parental responsibility, modern technology and media, overconsumption of
      unhealthy food, children's lack of knowledge and motivation, physical activity
      environment, lack of healthy food, lack of physical activity and genes. Two
      prevention factors were also derived, named government action and children's
      health promotion. Parents saw modern technology and media, and government
      activities as more important causes, and government policy as a more important
      means of prevention than nonparents and men. Women's responses tended to be
      similar to those of parents. There were few educational differences, although
      nontertiary educated respondents reported that modern technology and media were
      more important causes of obesity than did the tertiary educated. CONCLUSION: The
      findings suggest that the public appears to hold quite sophisticated views of the
      causes and prevention of children's obesity. They suggest that a number of
      prevention strategies would be widely supported by the public, especially by
      parents.

PMID- 14634677
TI  - The soluble leptin receptor is crucial for leptin action: evidence from clinical
      and experimental data.
AB  - OBJECTIVE: The soluble leptin receptor (sOB-R) was recently identified as the
      main leptin-binding protein in human blood. The aim of our study was to elucidate
      the effects of physiologically relevant amounts of sOB-R on leptin-induced
      proliferation in a cell model. SUBJECTS AND MEASUREMENTS: To determine molar
      ratios between sOB-R and leptin in vivo, we measured both parameters in the serum
      of 529 healthy children and adolescents. For our in vitro cell model, mouse pre-B
      cells, transfected with the long form of the murine leptin receptor (BAF3/L46),
      were incubated with recombinant human leptin at two different basal levels (0.5
      and 0.1 nM) and with the sOB-R at varying levels. The proliferative response of
      the cells was quantified by a (3)H-thymidine uptake assay. RESULTS: Significantly
      higher molar sOB-R/leptin ratios were observed during the first years of life, up
      to a 7.67-fold excess of sOB-R (quartiles: 4.43/10.27) in boys, compared to the
      states of prepuberty and puberty. An up to 10-fold molar excess of the sOB-R,
      reflecting the in vivo situation, resulted in a significant suppression of leptin
      action in the cell model. In contrast, gradually decreasing ratios of lower than
      two, as calculated during the progression of childhood and in early puberty,
      corresponded to proliferative rates in vitro as determined at basal leptin
      concentrations. CONCLUSION: At a distinct molar excess, sOB-R may suppress leptin
      action through inhibition of specific leptin binding to membrane-bound receptors
      in vitro. In vivo, sOB-R may further function to delay leptin clearance and
      increase the available leptin pool in the circulation. In the case of a massive
      excess of sOB-R, is it likely to be inhibitory to leptin interaction with the
      tissue membrane-bound OB-R.

PMID- 14634678
TI  - Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in
      response to a high-fat meal.
AB  - OBJECTIVE: To examine the short-term effects of a lipase inhibitor (Orlistat) on
      physiological and behavioural measures of appetite in response to a high-fat
      meal. DESIGN: Randomised, single blind, placebo-controlled, crossover trial.
      SUBJECTS: A total of 19 healthy nonobese male subjects. PROCEDURES: After an
      overnight fast, subjects ingested a test meal of 2940 kJ (60% fat, 30% CHO, 10%
      protein) with Orlistat (120 mg) or a placebo, separated by 2 weeks. Appetite, as
      assessed by a standard line scale, and plasma cholecystokinin (CCK)
      concentrations were measured prior to and every hour after the test meal for 4 h.
      Thereafter, subjects ingested a quantified, but self-selected portion of a
      standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final
      line scale questionnaire. RESULTS: The CCK response to the test meal was
      negatively correlated with BMI in both the Orlistat and placebo trials (R=-0.69
      and -0.65, P<0.01). Orlistat administration did not significantly alter the CCK
      response to the test meal (6.30+/-3.27 vs 7.36+/-3.94 pM min, for Orlistat and
      placebo, P=0.193). Similarly, the line scale measures of appetite and subsequent
      intake (520+/-205 vs 554+/-197 g, P=0.48) were not different between the trials.
      CONCLUSION: Orlistat administration did not alter short-term physiological or
      behavioural measures of satiety in response to a high-fat meal in healthy,
      nonobese subjects. The CCK response to a test meal may be partly determined by
      BMI.

PMID- 14634679
TI  - Weight loss in obese Mexican Americans treated for 1-year with orlistat and
      lifestyle modification.
AB  - OBJECTIVE: To evaluate the effectiveness of a culturally appropriate lifestyle
      intervention combined with orlistat in producing weight loss with obese Mexican
      American women. SUBJECTS: Mexican-American women (N=108), aged 21-65 y, with a
      body mass index (BMI) > or =27 kg/m(2) were randomized to 1 y of treatment with
      orlistat and a culturally tailored lifestyle modification intervention (OLM;
      n=56) or a wait-list control group (WLC; n=52). DESIGN: A randomized, controlled,
      open-label 12-month study. Orlistat was dosed at 120 mg, three times per day. The
      OLM intervention included behavior modification, a low-fat (< or =30% of total
      daily calories) diet, and moderate physical activity (> or =150 min/week).
      MEASUREMENT: Primary outcomes included changes in body weight (kg), BMI, waist
      circumference, blood pressure, glucose, and lipids. RESULTS: A total of 72 (37
      OLM, 35 WLC) and 66 participants (32 OLM, 34 WLC) completed the 6- and 12-month
      follow-ups, respectively. Repeated-measures ANOVA demonstrated a significant time
      x treatment interaction (Wilks' lambda=12.61; P<0.001), indicating that OLM
      treated patients achieved significant weight loss relative to the WLC group
      during the study (mean percentage weight loss+/-s.e.m.; -8.1%+/-1.2 vs -1.6%+/
      0.7 at 6 months and -8.8%+/-1.5 vs -0.2%+/-1.0 at 12 months, respectively). OLM
      treated patients also experienced significant reductions in waist circumference,
      low-density-lipoprotein, and total cholesterol. CONCLUSIONS: This study
      demonstrates the effectiveness of an intervention combining orlistat and
      lifestyle modification with Mexican-American women, a population with substantial
      risk for obesity.

PMID- 14634680
TI  - Effect of dietary restraint during and following pegylated recombinant leptin
      (PEG-OB) treatment of overweight men.
AB  - OBJECTIVE: To examine the effect of dietary restraint during and following
      pegylated recombinant leptin (PEG-OB protein) treatment in overweight men.
      DESIGN: A randomized double-blind placebo-controlled trial in 24 overweight men
      (BMI: 28.8+/-0.3 kg/m(2); age: 34.8+/-0.9 y). PEG-OB protein (80 mg) or placebo
      was administered subcutaneously weekly for 6 weeks, combined with a 2.1 MJ/day
      energy restriction program. Dietary restraint was determined by the Three-Factor
      Eating Questionnaire before and after treatment, and after 8 weeks follow-up.
      RESULTS: During treatment dietary restraint increased, and general hunger,
      resting energy expenditure and respiratory quotient decreased similarly in the
      PEG-OB and the placebo group. With PEG-OB treatment, additional weight loss
      (P<0.03) was observed. During 8 weeks follow-up, body weight increase was larger
      in the PEG-OB group compared to placebo (P<0.05), and body weight regain was
      faster. Body weight regain was inversely correlated with the increase in
      cognitive dietary restraint during treatment (PEG-OB group: r(2)=0.49, P<0.02;
      placebo group: r(2)=0.60, P=0.01). CONCLUSION: Although treatment with PEG-OB
      protein led to a greater body weight loss relative to placebo, weight maintenance
      thereafter was mainly supported by dietary restraint, which was more effective in
      the placebo-treated group, resulting in a slower regain of body weight.

PMID- 14634681
TI  - Technical skills for weight loss: 2-y follow-up results of a randomized trial.
AB  - OBJECTIVE: To investigate the sustained effectiveness of a novel skill-based
      intervention for weight loss. DESIGN: Randomized, controlled trial. SUBJECTS: A
      total of 80 overweight/obese women living in Connecticut. MEASUREMENTS: Absolute
      weight difference measured in pounds and absolute change in body mass index
      (BMI). Secondary outcomes included changes in food frequency questionnaire (FFQ)
      data and waist-to-hip ratio. RESULTS: In all 61, 35, and 34% of study
      participants completed the 6-, 12-, and 24-month assessments, respectively. At 6
      months postintervention, both counseling-based (CBI) and skill-based (SBI)
      intervention groups had statistically significant decreases in absolute weight
      (4.0+/-3.6 and 1.7+/-3.0 kg, respectively). Compared to their baseline values,
      both CBI and SBI groups still maintained weight losses at 24 months (1.1+/-5.8
      and 0.59+/-3.3 kg, respectively); however, the differences were not statistically
      significant. FFQ results showed that, within the SBI group, there was a
      significant decrease (P<0.05) in percent fat from baseline to 12 months and a
      nearly significant decrease in saturated fat from baseline to 24 months (P=0.07).
      CONCLUSIONS: Both the novel SBI and conventional dietary counseling demonstrated
      some residual weight loss benefit at 2 y. Effects of the SBI on dietary intake
      patterns are encouraging, and warrant further study.

PMID- 14634682
TI  - Obesity and central fat pattern among Greenland Inuit and a general population of
      Denmark (Inter99): relationship to metabolic risk factors.
AB  - OBJECTIVE: To investigate whether the obesity observed among the Inuit of
      Greenland and in a general Danish population was associated with the same degree
      of metabolic disturbances. DESIGN: Comparison of data from two population-based
      cross-sectional surveys conducted in 1999-2001. SUBJECTS: A total of 7892
      individuals aged 30-60 y, 1108 Inuit participants from the Greenland Population
      study, and 6784 Danish participants in the Danish Inter99 study. MEASUREMENTS:
      Height, weight, waist and hip circumference were measured, and BMI and waist-to
      hip ratio were calculated. The participants received a standard 75 g OGTT. s
      Triglyceride, s-HDL cholesterol, fasting and 2 h p-glucose and s-insulin were
      analysed. Blood pressure was measured. Information on lifestyle factors was
      obtained by a questionnaire and interview. RESULTS: The Inuit had lower levels of
      2-h glucose and insulin, blood pressure, triglyceride, and higher levels of HDL
      cholesterol than the Danish participants at any given level of obesity. Fasting
      glucose and fasting insulin levels within obesity categories were not different
      in the two populations. Adjustment for physical activity, smoking, school
      education, and alcohol consumption did not change these findings. CONCLUSION: The
      trends in the association between obesity and metabolic effects among the Inuit
      and a Northern European population were the same, but the levels of the risk
      factors were significantly different. This may be due to genetic factors and
      differences in body composition.

PMID- 14634683
TI  - Weight development over time in parous women--the SPAWN study--15 years follow
      up.
AB  - BACKGROUND: Weight gain is common after pregnancy. Most studies suggest that
      weight gain associated with a pregnancy is between 0.5 and 3.8 kg up to 2.5 y of
      follow-up. However, 73% of the female patients at our obesity clinic identified
      pregnancy as an important trigger for marked weight retention. The majority
      retained more than 10 kg after each pregnancy. The aim of this study was to
      examine long-term weight development after pregnancy in a 15 y follow-up of women
      who took part in the Stockholm Pregnancy And Women's Nutrition (SPAWN) study.
      METHOD AND SUBJECTS: The SPAWN study is a long-term follow-up study of women who
      delivered children in 1984-85 in Stockholm (n=2342). A total of 1423 participants
      (response rate=61%) completed questionnaires, which covered eating behaviour and
      exercise, demographic information including social situation and status and
      details of the pregnancy before, during and up to 1 y after pregnancy. After 15
      y, these women were invited to take part in the follow-up study. Anthropometric
      measurements and the same questionnaire data were collected from the 563 women
      who participated (response rate=40%). The sample was divided into two main
      groups: those who were normal weight before pregnancy and remained normal weight,
      and those who were normal weight before pregnancy and had become overweight at 15
      y follow-up. RESULTS: Those women who became overweight had a higher pre-pregnant
      body mass index (BMI) (22.3+/-1.5 vs 20.5+/-1.6 kg/m(2), P<0.001), gained more
      weight during pregnancy (16.3+/-4.3 vs 13.6+/-3.7 kg, P<0.001) and had retained
      more at 1 y follow-up. The women who became overweight had a steeper weight
      trajectory gaining more from 1 y follow-up to 15 y follow-up (11.1+/-6.5 vs 4.5+/
      6.5 kg, P<0.001), with a higher BMI at 15 y follow-up of 27.5+/-2.6 vs 22.5+/-2.3
      5 kg/m(2) (P<0.001). However, differences between those who became overweight and
      those who did not could not be explained by age, number of children and various
      socioeconomic factors. Features of pregnancy that did differ between the two
      groups were breastfeeding and smoking cessation. However, women who became
      overweight had lower lactation scores than women who remained normal weight.
      Relatively more subjects of the group that became overweight stopped smoking
      during pregnancy. DISCUSSION: Pregnancy is a vulnerability factor for some women
      to become overweight. This study attempted to identify those factors that place
      initially normal weight women on a steeper weight trajectory as a result of
      pregnancy. Demographic, behavioural, physical and psychological characteristics
      only partly explain the weight gain observed at 15 y follow-up. Further research
      is required to investigate the relative role of these characteristics in
      predicting postpregnancy weight development.

PMID- 14634684
TI  - Relationship between growth and feeding in infancy and body mass index at the age
      of 6 years.
AB  - OBJECTIVE: To assess the relationship between size and growth measurements in
      infancy to body mass index (BMI) at 6 y. DESIGN: A longitudinal observation study
      on randomly chosen infants' growth and consumption in infancy. Follow-up until
      the age of 6 y. SUBJECTS: A total of 90 children who were born healthy and full
      term. MEASUREMENTS: Weight and height were measured at maternity wards and
      healthcare centers in Iceland throughout infancy and at 6 y. Food records were
      made every month during infancy. At 2, 4, 6, 9 and 12 months, food was weighed to
      calculate food and nutrient intake. RESULTS: Weight gain from birth to 12 months
      as a ratio of birth weight was positively related to BMI at the age of 6 y in
      both genders (B=2.9+/-1.0, P=0.008, and B=2.0+/-0.9, P=0.032 for boys and girls,
      respectively). Boys in the highest quartile of protein intake (E%) at the age of
      9-12 months had significantly higher BMI (17.8+/-2.4 kg/m(2)) at 6 y than the
      lowest (15.6+/-1.0 kg/m(2), P=0.039) and the second lowest (15.3+/-0.8 kg/m(2),
      P=0.01) quartile. Energy intake was not different between groups. Together,
      weight gain at 0-12 months and protein intake at 9-12 months explained 50% of the
      variance in BMI among 6-y-old boys. CONCLUSION: Rapid growth during the first
      year of life is associated with increased BMI at the age of 6 y in both genders.
      In boys, high intake of protein in infancy could also contribute to childhood
      obesity.

PMID- 14634685
TI  - Energy cost of physical activities in 12-y-old girls: MET values and the
      influence of body weight.
AB  - BACKGROUND: Few data exist on the energy cost of specific activities in children.
      The influence of body weight on the energy cost of activity when expressed as
      metabolic equivalents (METs) has not been vigorously explored. OBJECTIVE: To
      provide MET data on five specific activities in 12-y-old girls and to test the
      hypothesis that measured MET values are independent of body weight. SUBJECTS AND
      METHODS: In 17 12-y-old girls, resting metabolic rate (RMR) and the energy
      expended while sitting, standing, walking on a flat treadmill at 3.2 and at 4.8
      km/h, and walking on a treadmill at a 10% incline at 4.8 km/h were measured using
      indirect calorimetry. MET values were calculated by dividing the energy
      expenditure of an activity by the subject's RMR. The influence of body weight was
      assessed using simple linear regression. RESULTS: The observed METs were more
      consistent with published values for similar activities in adults than those
      offered for children. Body weight was a statistically significant predictor of
      the MET of all three walking activities, but not the MET of sitting or standing.
      Body weight explained 25% of the variance in the MET value for walking at 3.2
      km/h, 39% for walking at 4.8 km/h, and 63% for walking at a 10% incline at 4.8
      km/h. CONCLUSION: METs for the three walking activities were not independent of
      body weight. The use of average MET values to estimate the energy cost of these
      three activities would result in an underestimation of their energy cost in
      heavier girls and an overestimation in lighter girls. These results suggest that
      the estimation of total energy expenditure from activity diary, recall, and
      direct observation data using average MET values may be biased by body weight.

PMID- 14634686
TI  - Severe obesity and personality: a comparative controlled study of personality
      traits.
AB  - OBJECTIVE: The primary purpose was to assess personality trait differences
      between the severely obese seeking treatment and a mainly non-obese reference
      group. We also investigated gender differences and differences between obese
      patients and obese not seeking treatment. METHOD: Personality traits were
      assessed using 7 of 15 scales from the Karolinska Scales of Personality (KSP):
      Somatic Anxiety, Muscular Tension, Psychastenia, Psychic Anxiety, Monotony
      Avoidance, Impulsiveness, and Irritability. Patients from the Swedish Obese
      Subjects (SOS) intervention study (n=3270, ages 37-57, 71% women) and the SOS
      reference study (n=1135, 54% women) completed the survey. Data presented in this
      study were gathered prior to treatment. Significance tests and effects sizes were
      calculated. RESULTS: Although statistically significant differences were found
      between obese patients and reference subjects on nearly all personality traits,
      effect sizes were at most moderate. Of the three scales with moderate effects
      sizes, differences on Somatic Anxiety and Psychastenia could be traced to items
      tapping condition-specific symptoms, e.g., problems with sweating and breathing
      as indicators of Somatic Anxiety. Moderate differences on the Impulsiveness scale
      (men alone) could not be explained by item composition. Further, the obese
      patients differed from obese in the reference group, and both obese and reference
      women reported significantly higher levels on Somatic Anxiety, Muscular Tension
      and Psychic Anxiety compared to men (effect size: small). CONCLUSIONS: Our
      results provided no evidence of a general obese personality profile, instead
      considerable heterogeneity in personality traits was observed across our obese
      samples (treatment seekers vs non-seekers, men vs women) and generally only small
      differences were noted compared to a reference study population. Further research
      is needed to investigate if the somewhat elevated levels of Impulsiveness,
      particularly among male obese patients, is affected by weight loss. When
      assessing personality traits in diseased groups consideration should be given to
      possible confounding from, e.g., somatic symptoms.

PMID- 14634687
TI  - Obesity is associated with impaired coronary collateral vessel development.
AB  - BACKGROUND: Chronic myocardial ischaemia due to coronary artery stenosis or
      occlusion has been shown to increase the growth of coronary collateral
      circulation. Collateralization leads to increased oxygen delivery to the area at
      risk and hence may reduce ischaemia, prevent infarction and preserve contractile
      function. However, there is considerable variation among patient subsets in terms
      of the presence or degree of collateralization. We aimed to evaluate the
      relationship between obesity and coronary collateral development in patients with
      ischaemic heart disease. METHODS AND RESULTS: In all, 215 patients (mean age,
      57.8+/-8.9 y) with body mass index (BMI)> or =30 kg/m(2) were enrolled into our
      study. A total of 90 age- and sex-matched patients (mean age, 58.7+/-10 y) with
      BMI<25 kg/m(2) and significant coronary artery disease were selected as a control
      group. The mean age and distribution of risk factors for coronary heart disease
      were not significantly different between two groups other than poorer HDL
      cholesterol and triglyceride profile in obese patients. The mean BMI was
      significantly higher in the patient group (33.3+/-2.4 vs 22.8+/-1.7, P<0.001).
      The mean number of diseased vessels and maximum lesion severity were not
      significantly different between the two groups. The mean Rentrop collateral score
      of the patient group was significantly worse than the control group (1.08+/-0.68
      vs 2.10+/-0.72, P<0.001). CONCLUSIONS: Our findings suggest that collateral
      vessel development is poorer in obese patients (defined as BMI> or =30 kg/m(2))
      with ischemic heart disease compared to normal range BMI, and the risk of having
      poor collateral vessel development is significantly increased. However, this
      might be reflecting the cluster of risk factors, associated with metabolic
      syndrome, in which insulin resistance plays a major role.

PMID- 14634688
TI  - Abdominal obesity and carotid artery wall thickness. The Los Angeles
      Atherosclerosis Study.
AB  - OBJECTIVE: To determine whether or not abdominal obesity is associated with the
      intima-media thickness (IMT) of the carotid artery wall independently of total
      body obesity and major risk factors for atherosclerosis. DESIGN: : Longitudinal
      epidemiological study. SUBJECTS: A total of 573 middle-aged employees of a
      utility company. MEASUREMENTS: Sagittal and transverse abdominal diameters, their
      ratio and difference were used as measures of abdominal obesity. RESULTS:
      Abdominal diameters and body mass index (BMI) were significantly associated with
      blood pressure, serum lipoproteins and fasting insulin. In cross-sectional
      multiple regression models, the sagittal/transverse ratio and BMI were
      significantly associated with IMT in the presence of atherosclerosis risk, but
      the sagittal diameter was not. In longitudinal models, baseline BMI was an
      independent predictor of IMT progression but the sagittal and transverse
      diameters were not. CONCLUSION: These findings do not support the hypothesis that
      abdominal obesity is an independent predictor of carotid artery IMT. The
      consistent pattern of association of measures of general obesity with carotid
      artery IMT emphasizes the continuing need for prevention and control of this
      important risk factor.

PMID- 14634689
TI  - Butyrylcholinesterase and obesity in individuals with the CHE2 C5+ and CHE2 C5-
      phenotypes.
AB  - OBJECTIVE: To investigate the association between butyrylcholinesterase (BChE)
      activities (total and band specific) and body mass index (BMI) in obese and
      nonobese individuals, considering other variables (anthropometric, biochemical
      and hormonal) and the leanness process. SUBJECTS: Obese (BMI> or =30 kg/m(2);
      N=181) and nonobese individuals (N=265), classified according to the CHE2 locus
      phenotypes, with the obese patients being followed-up when submitted to a weight
      loss program. MEASUREMENTS: Anthropometric (weight, height, BMI, waist, waist/hip
      ratio-WHR, triceps and subscapular skinfolds, percentage of body fat and arterial
      pressures), hormonal (insulin, estradiol-E(2), triiodothyronine-T(3) and
      thyroxine-T(4)) and biochemical (glucose, total cholesterol, HDL-C,
      triglycerides, uric acid, urea, creatinine, sodium, potassium and BChE
      activities) variables. RESULTS: Although obese CHE2 C5- individuals presented
      higher mean BChE activities than their CHE2 C5- controls and diminished mean
      activities with leanness, similar comparisons did not show any difference in the
      CHE2 C5+ group. Furthermore, the mean serum potassium values of obese individuals
      were significantly higher in the CHE2 C5+ than in the CHE2 C5- phenotype. The
      BChE activities were less related to BMI in obese CHE2 C5- individuals than in
      their controls. In the CHE2 C5- obese group, significant regression coefficients
      were found between BChE activity variables and BMI (+), ethnic origin (higher in
      Euro-Brazilians), sex (higher in males), diastolic pressure (-), triceps skinfold
      (+), total cholesterol (+), T(3) (+) and E(2) (-). The main findings in the CHE2
      C5+ obese group: mean insulin levels decreased with leanness and a significant
      correlation was detected between the C(5) complex activity and creatinine (+),
      insulin (-) and WHR (-); a significantly higher frequency of weight loss occurred
      compared to the CHE2 C5- group. CONCLUSION: In the present study, different
      relations between obesity and some of the studied variables were found when CHE2
      C5+ and CHE2 C5- individuals were compared.

PMID- 14634690
TI  - Abstracts of the 3rd International Symposium on Obesity and Hypertension Genetics
      and Molecular Mechanisms. 23-25 October 2003, Berlin, Germany.

PMID- 14634693
TI  - Recepteurs a la Provencale. EMBO workshop on the biology of nuclear receptors.

PMID- 14634694
TI  - The order of rafts. Conference on microdomains, lipid rafts and caveolae.

PMID- 14634695
TI  - The mbk-2 kinase is required for inactivation of MEI-1/katanin in the one-cell
      Caenorhabditis elegans embryo.
AB  - The Caenorhabditis elegans early embryo is widely used to study the regulation of
      microtubule-related processes. In a screen for mutants affecting the first cell
      division, we isolated a temperature-sensitive mutation affecting pronuclear
      migration and spindle positioning, phenotypes typically linked to microtubule or
      centrosome defects. In the mutant, microtubules are shorter and chromosome
      segregation is impaired, while centrosome organization appears normal. The
      mutation corresponds to a strong loss of function in mbk-2, a conserved
      serine/threonine kinase. The microtubule-related defects are due to the
      postmeiotic persistence of MEI-1, a homologue of the microtubule-severing protein
      katanin. In addition, P-granule distribution is abnormal in mbk-2 mutants,
      consistent with genetic evidence that mbk-2 has other functions and with the
      requirement of mbk-2 activity at the one-cell stage. We propose that mbk-2
      potentiates the degradation of MEI-1 and other proteins, possibly via direct
      phosphorylation.

PMID- 14634697
TI  - Duodenorenal fistula.
AB  - We describe two children (ages 5 and 13 years) with duodenorenal fistula. One
      fistula was due to perforation of the duodenum and renal migration of an ingested
      toothpick. The second fistula was caused by a chronic perinephric abscess. Both
      children underwent surgical fistula closure and right nephrectomy.

PMID- 14634696
TI  - Intussusception. Part 2: An update on the evolution of management.
AB  - Children with symptomatic ileocolic or ileo-ileocolic intussusceptions can be
      successfully managed in one of a number of different ways. The nonoperative enema
      reduction technique has major advantages over surgical reduction and high success
      rates can be achieved using pneumatic or hydrostatic reduction techniques under
      fluoroscopic or sonographic guidance. This article highlights current concepts
      and some controversial issues related to management of intussusception, including
      patient selection for attempted enema reduction, the advantages and disadvantages
      of each technique, complications, the value of delayed, repeated reduction
      attempts, the role of imaging after attempted enema reduction, and recurrence of
      intussusception.

PMID- 14634698
TI  - Transmural migration of gastrostomy tube retention discs.
AB  - BACKGROUND: Accidental dislodgment is one of the most frequent causes of
      avoidable cost and consternation related to gastrostomy tubes. The Sacks-Vine
      gastrostomy tube, inserted in an antegrade fashion by a percutaneous technique,
      is extremely stable due to the construction of its disc retention device.
      However, transmural migration of the retention disc is a known severe delayed
      complication associated with this tube. OBJECTIVE: To review the presentation,
      diagnosis, and treatment of transmural migration of gastrostomy retention discs,
      to propose a mechanism for the progressive development of this complication, and
      to recommend a method for preventing its occurrence. MATERIALS AND METHODS: From
      January 1991 to October 1999, pediatric interventional radiologists at two
      children's hospitals performed 300 antegrade gastrostomy and gastrojejunostomy
      primary insertion procedures. A "push-pull" variation of the antegrade approach
      used for 44 of these insertions is excluded from further analysis. Of the
      remaining 256 procedures, 5 boys and 3 girls with a mean age of 5.1 years (range
      0.8-19 years) were identified from review of the prospectively gathered
      procedural database with significant complications related to the disc retention
      component of their gastrostomy tubes. A retrospective analysis was conducted of
      their medical records, diagnostic imaging, and interventional and surgical
      findings. RESULTS: Transmural migration was diagnosed on average 36 months after
      insertion (16-48 months). The diagnosis was made incidentally during endoscopy
      (n=1) or fluoroscopy (n=5) in six asymptomatic patients, and during barium enema
      to explore feculent vomiting and halitosis in two symptomatic patients. Migration
      of the retention disc fell along a continuum from intramural (n=4) to transmural
      and intracolonic (n=4), with gastric mucosal erosion, extensive granulation and
      inflammation in all eight patients. Although there was no evidence of free air in
      any patient, a gastrocolic fistula was demonstrated in four patients and a
      gastrocolocutaneous fistula in two of four patients with complete transmural
      migration. Surgical resection of the disc, gastrostomy, and fistula repair if
      needed was successfully performed in all patients. CONCLUSIONS: Gastrostomy tubes
      with an internal retention disc are at risk for progressive disc migration into
      and through the gastric wall, resulting in irretrievable fixation and potential
      fistula formation. This severe delayed complication results from prolonged
      traction on the retention disc. Transmural migration may be avoided through
      improved tube care education, daily disc mobilization, and earlier disc
      retrieval.

PMID- 14634699
TI  - Hormonal counterregulation and consecutive glimepiride serum concentrations
      during severe hypoglycaemia associated with glimepiride therapy.
AB  - OBJECTIVE: To examine the release of counterregulatory hormones and consecutive
      glimepiride serum concentrations during severe hypoglycaemia (SH) associated with
      glimepiride therapy. METHODS: In nine type-2 diabetic patients [age 81+/-9 (65
      93) years; diabetes duration 9+/-4 (3-15) years; initial blood glucose 33+/-16
      (10-54) mg/dl (1.8+/-0.9 mmol/l); HbA1c 7.2+/-1.1 (5.6-8.7)%; creatinine
      clearance 49+/-33 (15-107) ml/min] who experienced SH associated with glimepiride
      therapy with neuroglucopenic presentation, insulin, C-peptide, glucagon,
      epinephrine, norepinephrine, cortisol, adenocorticotrophic hormone (ACTH), human
      growth hormone (HGH) and pancreatic polypeptide (PP) were determined in blood
      samples taken at 4-h intervals prior to and during treatment with glucose i.v.
      Serum from the same samples was screened for sulphonylurea-type oral
      antidiabetics. Glimepiride concentrations were determined by a validated
      atmospheric pressure chemical ionization liquid chromatographic-mass spectrometry
      (APCI-LC-MS) assay. RESULTS: Once treatment had begun, normoglycaemia was
      maintained; most glimepiride levels were below the limit of detection (LOD <0.01
      mg/l) and further sulphonylureas could be excluded. The secretion of glucagon and
      epinephrine as counterregulatory hormonal responses was unaffected. In addition,
      protracted marked increases of cortisol and norepinephrine levels were
      demonstrated. Protracted stimulation of insulin and C-peptide occurred in a
      period of up to 24 h after SH. No significant protracted responses were observed
      for ACTH, HGH or PP. CONCLUSION: In SH associated with glimepiride therapy, no
      correlation between glimepiride serum concentrations and the protracted
      stimulation of insulin and C-peptide was observed. The secretion of glucagon and
      epinephrine as counterregulatory hormonal responses was unaffected. Protracted
      increased release of cortisol might be a medium-term indicator of glimepiride
      associated SH.

PMID- 14634700
TI  - Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine
      tolerant and -intolerant patients with various disorders. The impact of TPMT
      genotyping in predicting toxicity.
AB  - OBJECTIVE: To study the distribution of the thiopurine methyltransferase (TPMT)
      genotype among azathioprine (Aza)-tolerant and -intolerant patients with various
      disorders, and to investigate a possible relationship with the Aza metabolite
      levels. METHODS: Forty-six Aza-tolerant and six Aza-intolerant patients had the
      TPMT genotype distribution determined using a polymerase chain reaction (PCR)
      assay and the forty-six Aza-tolerant patients had the Aza metabolite levels
      determined using a high-pressure liquid chromatography (HPLC) analysis. RESULTS:
      One non-functional TPMT mutant allele was demonstrated in 2 of the 46 Aza
      tolerant patients (4.4%) and one or two non-functional mutant alleles in 2 of the
      6 Aza-intolerant patients (33.3%). Of the 4 patients, with one or two non
      functional mutant alleles 2 (50%) were intolerant to Aza compared with 4 of the
      48 patients (8.3%) with no mutations detected. The time to hepatotoxicity did not
      differ significantly between the 2 patients with one or two non-functional mutant
      alleles and the remaining 3 patients ( P=0.5). The TPMT genotype distribution
      differed slightly in the three different categories of disorders ( P=0.05). The
      median E-6-TGN level among the 2 TPMT heterozygous patients was 275 pmol/8x10(8)
      RBC (range 240-310), whereas the remaining 44 patients had a median E-6-TGN level
      of 110 pmol/8x10(8) RBC (range 0-440) ( P=0.07). CONCLUSION: Although TPMT
      genotyping cannot be recommended on behalf of the present study, it is to be
      expected that half of the patients with one or two non-functional TPMT mutant
      alleles will develop Aza intolerance leading to withdrawal of therapy. Thus,
      clinicians may anticipate about 5% of the patients to develop intolerance to Aza
      therapy solely for that reason.

PMID- 14634702
TI  - Liquid chromatography coordination ion-spray mass spectrometry (LC-CIS-MS) of
      docosahexaenoate ester hydroperoxides.
AB  - Coordination ion-spray mass spectrometry (CIS-MS) is a useful tool in the
      detection and identification of complex mixtures of cholesterol ester and
      phospholipid hydroperoxides. The methyl ester, cholesterol ester, and
      phospholipid hydroperoxides of docosahexaenoic acid were analyzed by LC-CIS-MS
      and their elution orders were identified. Their corresponding alcohols were also
      identified. The methyl hydroperoxydocosahexaenoate (HPDHE) elution order is 14,
      17, 16, 13, 20, 11, 10, 4, 7, 8 while the methyl hydroxydocosahexaenoate (HDHE)
      elution order is 14 > or = 17, 16, 13, 11, 10, 20, 7, 8, 4. The cholesteryl HPDHE
      elution order is 14, 17, 16, 13, 20, 11 > or = 10, 4, 7, 8 and the cholesteryl
      HDHE elution order is 17, 14, 16, 13, 11, 20, 10, 7, 8, 4. The elution order of
      the 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphatidylcholine (PDPC)
      hydroperoxides and alcohols is 20, 16, 17, 13, 14, 10, 11, 7, 8, 4.

PMID- 14634703
TI  - Specific properties of fine SnO2 powders connected with surface segregation.
AB  - The effect of surface segregation in Sb- and In-doped SnO2 fine-grained powders
      has been analyzed in comparison with single-crystalline samples. The kinetics and
      thermodynamics of the Sb and In segregation processes were studied as a function
      of annealing temperature by X-ray photoelectron spectroscopy (XPS) after
      annealing in an oxygen-containing atmosphere. Significant differences between
      diffusion and segregation were revealed for doped powders and single crystals,
      obviously because of simultaneous diffusion and particle-growth processes
      proceeding during annealing of powders. For doped single crystals the
      thermodynamic equilibrium is approached after 24 h annealing above 850 degrees C
      and at 1000 degrees C for Sb and In, respectively. Higher effective activation
      energies of diffusion are observed for doped powders and the thermodynamic
      equilibrium is not achieved under technologically relevant annealing conditions.
      On the basis of dopant profile measurements anomalies in the electrical
      resistivity at 300 degrees C of Sb-doped SnO2 powders annealed at 700 and 900
      degrees C were attributed to an Sb-depleted zone formed beneath the segregated
      surface during the kinetic regime. To achieve optimum resistivity behavior for
      commercial application, inhomogeneous doping of powders must be avoided by
      appropriate preparation steps.

PMID- 14634704
TI  - Water sorption properties of carbonized layers produced by controlled B+
      bombardment of thin polyimide and polysulfone films.
AB  - Thin polyimide (PI) and polyethersulfone (PES) films are widely used as
      functional layers for microelectronic sensors. Ion implantation modifies the
      layer structure and morphology of these polymers and hence results in new
      mechanical and optical properties. However, ion-modified layers also show a
      change in sensitivity to moisture uptake under specific conditions. This is
      important for developing humidity sensors. Therefore, the water sorption ability
      of such modified polymer layers is studied by spectroscopic ellipsometry under
      definite relative humidity conditions (1-95%). Swelling data were obtained by
      fitting procedures based on changes of effective layer thickness and optical
      constants due to water uptake. Irradiation doses from 0.5 to 5x10(15) B+ cm(-2)
      at an energy of 180 keV were used for polymer modification. At irradiation doses
      from 0.5 to 0.7x10(15) B+ cm(-2), the maximum out-of-plane swelling is reached.
      At higher doses >2x10(15) B+ cm(-2), the swelling decreases and corresponds to
      values of the pure polymer layers. The wetting properties of the layer surfaces
      determined by contact angle measurements are important to explain this behavior.

PMID- 14634705
TI  - A simple device for the extraction of TLC spots: direct coupling with an
      electrospray mass spectrometer.
AB  - A new device is described which allows the recovery of compounds from thin layer
      chromatograms in short times, within a small volume, and without contamination.
      This apparatus can be coupled online to an electrospray mass spectrometer, but
      can also be used with other detectors or for micropreparations.

PMID- 14634706
TI  - Structural study of spirolide marine toxins by mass spectrometry. Part II. Mass
      spectrometric characterization of unknown spirolides and related compounds in a
      cultured phytoplankton extract.
AB  - The spirolides are a family of marine biotoxins derived from the dinoflagellate
      Alexandrium ostenfeldii, recently isolated from contaminated shellfish and
      characterized. A crude phytoplankton extract has been extensively studied for
      mass spectrometric determination and characterization of several known spirolides
      and previously unreported compounds. The complex sample was initially analyzed by
      full-scan mass spectrometry in an ion-trap instrument, enabling identification of
      several components. Subsequent analysis by selected-ion monitoring in a triple
      quadrupole instrument resulted in the confirmation of the identities of the
      compounds detected in the ion trap. Purification of the crude extract was
      performed using an automated mass-based fractionation system, yielding several
      fractions with different relative contributions of the spirolide components.
      Collision-induced dissociation (CID) in the triple-quadrupole instrument produced
      significant fragment ions for all identified species. Selective enrichment of
      some minor compounds in certain fractions enabled excellent CID spectra to be
      generated; this had previously been impossible, because of interferences from the
      major toxins present. Fourier-transform ion cyclotron resonance (FTICR) mass
      spectrometry was then performed for accurate determination of the masses of MH+
      ions of all the species present in the sample. Additionally, infrared multiphoton
      dissociation in the FTICR instrument generated elemental formulae for product
      ions, including those formed in the previous collisional activation experiments.
      Collection of these results and the fragmentation scheme proposed for the main
      component of the extract, 13-desmethyl spirolide C, from part I of this study,
      enabled elucidation of the structures of some uncharacterized spirolides and some
      biogenetically related compounds present at previously unreported masses.

PMID- 14634707
TI  - A rapid enzyme assay for beta-galactosidase using optically gated sample
      introduction on a microfabricated chip.
AB  - The ability to perform enzyme assays on microchips is demonstrated using
      optically gated sample introduction. The hydrolysis of fluorescein mono- beta- d
      galactopyranoside (FMG) by beta- d-galactosidase ( beta-Gal) is continuously
      monitored using a microchip for 5 to 10 min. The outcome of the reaction was
      analyzed by performing serial on-chip separations of fluorescent substrate, FMG,
      and product, fluorescein. Kinetic information about beta-Gal has been
      successfully obtained by varying the concentration of FMG. beta-Gal enzymes from
      two different sources including bovine liver and E. coli., have been examined and
      compared to each other and to results obtained using traditional assay methods.
      In addition, the competitive inhibition of beta-Gal by phenylethyl beta- d
      thiogalactoside (PETG) and beta-lactose has been studied using this technique.
      PETG is found to have higher inhibition than lactose in the hydrolysis. This
      separation-based enzyme assay technique avoids the possible fluorescence
      interference between FMG and fluorescein, which is a problem with the traditional
      plate assay method. Additionally, the amount of the enzyme and substrate required
      with this technique is at least four orders of magnitude lower than the
      traditional plate assay method. By using optically gated sample introduction,
      microchips allow continuous serial injections and separations without any
      potential switch, thus making this technique ideal as a sensor for enzyme assays.
      This technique should therefore be valuable for high-throughput screening in the
      drug discovery industry.

PMID- 14634708
TI  - Stable isotope variation as a tool to trace the authenticity of beef.
AB  - Organic beef coming principally from Germany was analysed for the hydrogen,
      carbon, oxygen, nitrogen and sulfur stable isotopic composition to test the
      possibility of tracing back the geographical origin. Since there is a well-known
      pattern of D/H and 18O/16O in meteoric water and in ground water, there is an
      existing link to tissue water in the beef. By including the stable isotope ratios
      of the other elements of life further information is available: soils show
      different isotope ratios of 15N/14N and 34S/32S depending on the geological
      composition, cultivation and atmospheric sulfur deposition. As organic farming is
      mainly obliged to use only their produced fodder, that ratio is reflected in the
      beef as well. Different organic beef samples from various German farms have been
      collected and analysed over nearly two years. To check the differentiation of
      foreign beef, samples from Argentina and Chile were also included in the study.
      The analyses of meat samples indicate that it is possible to trace back the
      region (e.g. Argentina and Germany) by using isotopes of oxygen and hydrogen. A
      local geographical differentiation can be done by using the stable isotopes of
      nitrogen and sulfur, as was demonstrated for three farms in Colonia Bay. An
      optimal differentiation also depends on the quality of further information (e.g.
      the season, kind of cattle breeding or the declaration of the local geographical
      origin). Certainly authenticity of beef is not only linked with the geographical
      origin but can also reflect the differentiation of organic and conventional
      farming. The fodder of organic cattle farming consists mainly of C3 plants and
      the use of C4 plants is more usual in conventional cattle farming. A 13C/12C
      ratio above -20 per thousand appears as a limit for organic farming. Increased
      values have to be controlled based on their authenticity.

PMID- 14634709
TI  - Response to: Parrott AC, Buchanan T, Heffernan TM, Scholey A, Ling J, Rodgers J
      (2003) Parkinson's disorder, psychomotor problems and dopaminergic neurotoxicity
      in recreational ecstasy/MDMA users. Psychopharmacology 167(4):449-450.

PMID- 14634710
TI  - The reality of psychomotor problems, and the possibility of Parkinson's disorder,
      in some recreational ecstasy/MDMA users: a rejoinder to Sumnall et al. (2003).

PMID- 14634711
TI  - Reduced isolation-induced aggressiveness in mice following NAALADase inhibition.
AB  - RATIONALE: Long-term individual housing increases aggressive behavior in mice, a
      condition termed isolation-induced aggression; this aggressiveness is reduced by
      some antidepressants and anxiolytics. NMDA antagonists also inhibit isolation
      induced aggression in mice. The enzyme N-acetylated-alpha-linked acidic
      dipeptidase (NAALADase) hydrolyzes the neurotransmitter N-acetylaspartylglutamate
      (NAAG) to form glutamate and N-acetylaspartate; NAAG acts as a partial NMDA
      agonist as well as a full agonist at the presynaptic metabotropic glutamate
      receptor 3 (mGluR3), where it acts to reduce glutamate release. OBJECTIVE: We
      postulated that NAALADase inhibition would reduce isolation-induced aggression in
      mice. METHODS: We tested whether acute exposure to the NAALADase inhibitor 2
      [[hydroxy[2,3,4,5,6-pentafluorophenyl)methyl]phosphinyl]methyl] pentanedioic acid
      (GPI-5232), administered 30 min prior to a social interaction test, would inhibit
      aggressive behavior in SJL mice that had been individually housed long term.
      RESULTS: Administration of GPI-5232 (30 mg/kg, IP) inhibited initiation of
      aggressive behavior, indicated by greater latencies to display tail-rattling,
      attack and biting, and by fewer mice initiating aggressive behavior, compared to
      mice that received vehicle. In addition, GPI-5232 treated mice had fewer tail
      rattling responses to a non-aggressive conspecific. CONCLUSIONS: The
      effectiveness of GPI-5232 in this animal model suggests that NAALADase inhibition
      may be a novel therapeutic approach to reduce or inhibit heightened
      aggressiveness, and possibly to treat aggressive behavior associated with
      psychiatric disorders.

PMID- 14634712
TI  - Sex differences in the pituitary-adrenal response following acute antidepressant
      treatment in sheep.
AB  - RATIONALE: Depression is more prevalent in women than in men, and therapeutic
      responses may also differ between the sexes. In addition, abnormal regulation of
      the hypothalamic-pituitary-adrenal (HPA) axis is more common in depressed women.
      OBJECTIVES: To further examine these phenomena, the present study was designed to
      investigate whether sex differences exist in the HPA axis responses of male and
      female sheep following acute antidepressant administration. METHODS: Two commonly
      prescribed antidepressants, imipramine (a tricyclic antidepressant, TCA; 2.0 and
      5.0 mg/kg) and sertraline (a selective serotonin reuptake inhibitor, SSRI; 0.5,
      2.0 and 5.0 mg/kg) were administered to gonadectomized male and female sheep via
      acute subcutaneous injection. Treatment order was randomized. Jugular blood was
      sampled for the measurement of prolactin, adrenocorticotropin (ACTH), and
      cortisol by radioimmunoassay. RESULTS: Treatment with sertraline resulted in a
      comparable increase in prolactin secretion in male and female sheep. However,
      sertraline stimulated ACTH and cortisol secretion in females but not in males, a
      sexually dimorphic effect that was independent of circulating sex steroids.
      Treatment with imipramine had no effect on prolactin, ACTH or cortisol levels in
      male or female sheep. CONCLUSIONS: These data suggest that the HPA axes of
      females are more sensitive to the stimulatory effects of serotonin following
      acute treatment with the SSRI, sertraline.

PMID- 14634713
TI  - Cannabinoids modulate ultrasound-induced aversive responses in rats.
AB  - RATIONALE: Mechanisms and brain substrates mediating cannabinoid-induced
      modulation of behaviour towards aversive stimuli are poorly understood.
      OBJECTIVES: To investigate the effects of systemic and intra-dorsal
      periaqueductal grey (PAG) administration of the cannabinoid receptor agonist
      HU210 on behaviour and plasma corticosterone levels in rats exposed to ultrasound
      and determine the contribution of CB(1) receptors. METHODS: In experiment 1, rats
      received vehicle or CB(1) receptor antagonist SR141716A (3 mg/kg, IP) 30 min
      prior to a second injection of vehicle or HU210 (5, 20 or 80 microg/kg, IP). In
      experiment 2, rats received intra-dorsal PAG vehicle or SR141716A (30 microg/rat)
      10 min prior to intra-dorsal PAG vehicle or HU210 (5 microg/rat). Following
      injections, rats were exposed to an aversive 20 kHz ultrasonic tone for 3 min.
      Behaviour, including hyperlocomotor activity and freezing, was monitored during
      and post-ultrasound. Plasma corticosterone levels 10 min post-ultrasound were
      measured. RESULTS: Ultrasound induced explosive running and freezing behaviour.
      Systemic administration of HU210 attenuated the expression of ultrasound-induced
      hyperlocomotor activity and increased freezing. The HU210-induced attenuation of
      hyperlocomotor activity was blocked by SR141716A. Intra-PAG administration of
      HU210 reduced the expression of ultrasound-induced hyperlocomotor activity, an
      effect not blocked by SR141716A. Systemic and intra-PAG administration of HU210
      increased plasma corticosterone levels, an effect not blocked by SR141716A.
      CONCLUSIONS: The cannabinoid receptor agonist HU210 modulates behaviour towards
      an aversive ultrasound stimulus in rats, an effect accompanied by increased HPA
      axis activity. These effects may be mediated, at least in part, by the dorsal PAG
      but cannot be explained solely by an action at CB(1) receptors.

PMID- 14634714
TI  - Abuse liability and stimulant properties of dextromethorphan and diphenhydramine
      combinations in rats.
AB  - RATIONALE: The abuse of over-the-counter (OTC) medications has been widely
      reported. However, there are few preclinical studies examining the behavioral
      effects of OTC medications at higher, abused doses. OBJECTIVES: The objectives of
      the current study were to determine whether the anti-histamine diphenhydramine
      (DIP) and the antitussive dextromethorphan (DEX), either alone or in combination,
      would have stimulant properties and be self-administered in animals. METHODS: For
      drug self-administration, naive rats with no history of exposure to other drugs
      were trained to self-administer i.v. DEX+DIP (0.5+0.5, 1+1 or 2+2 mg/kg per
      injection), DEX alone (1 mg/kg) or DIP (1 mg/kg) alone under five-response fixed
      ratio (FR) schedule with a 30-s time-out after each injection in 2-h sessions 3-5
      days a week. Separate groups of rats were tested on locomotor activity. After 8
      consecutive days of habituation, naive rats were injected with 3, 10, or 30 mg/kg
      DEX or DIP alone i.p., or in combination of 3+3 mg/kg, 10+10 mg/kg, or 30+30
      mg/kg DEX+DIP i.p. Saline was injected i.p. during the intervening days.
      Locomotor activity was measured for each session. RESULTS: DEX+DIP combinations
      were self-administered, but the drugs alone were not. The acquisition of DEX+DIP
      self-administration was rapid with a majority of rats reaching the final FR5
      schedule in 22-23 sessions. The total i.v. combination dose for each final
      scheduled session ranged from 40 mg/kg to 160 mg/kg DEX+DIP. Significant
      increases in locomotor activity were observed for DIP, an effect that was
      significantly enhanced when DIP was given in combination with DEX. Significant
      mortality was also observed for the drug combination at each dose tested when
      given i.v., with the highest mortality following the highest dose (2+2 mg/kg).
      When given i.p., no mortality was observed. CONCLUSIONS: These results show that
      combinations of DEX and DIP have stimulant properties and are self-administered
      by animals. Abuse of this combination in humans would be expected.

PMID- 14634715
TI  - Unconditional hyperactivity and transient reinforcing effects of NMDA
      administration into the ventral tegmental area in rats.
AB  - RATIONALE: The dopaminergic projection from the ventral tegmental area (VTA) to
      the nucleus accumbens plays an important role in positive reinforcement and
      locomotion. Intra-VTA administration of many drugs capable of activating these
      neurons has been shown to be reinforcing and induce locomotion. Administration of
      the excitatory amino acid NMDA (N-methyl-D-aspartate) into the VTA may likewise
      be positively reinforcing, because it stimulates the meso-accumbens dopamine
      system and locomotion. OBJECTIVES AND METHODS: Locomotor-rearing experiments were
      conducted to pinpoint the range of NMDA concentrations that induce significant
      locomotion and rearing, and to determine whether co-administration of the glycine
      binding site agonist d-serine would enhance the effects of NMDA administration
      into the VTA. Reinforcing effects of NMDA were assessed by intracranial self
      administration procedures: a lever-press delivered a 75-nl infusion containing
      NMDA (0.1, 0.3 or 1.0 mM) plus serine into the VTA or an adjacent region, the
      supramammillary nucleus. RESULTS: Co-administration of serine slightly enhanced
      rearing induced by NMDA administration. Administration of NMDA at concentrations
      of 0.3 or 1.0 mM (500 nl) induced vigorous locomotion and rearing. NMDA (0.3 mM)
      was self-administered into the VTA slightly more than vehicle in the first or
      second sessions, yet this small reinforcing effect became irregular in subsequent
      sessions. The rats did not learn to self-administer NMDA into the supramammillary
      nucleus. CONCLUSIONS: Ventral tegmental NMDA injections, in the concentration
      range that induced marked unconditional hyperactivity, supported only marginal
      and transient self-administration.

PMID- 14634716
TI  - Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with
      schizophrenia.
AB  - OBJECTIVE: Alcohol abuse in patients with schizophrenia is associated with
      psychiatric and social complications. While two medications have been approved by
      the Federal Drug Administration (FDA) for the treatment of alcoholism: disulfiram
      and naltrexone, no medications have been approved for individuals with alcohol
      dependence and comorbid schizophrenia. The purpose of this study was to evaluate
      the efficacy of naltrexone in alcohol-abusing schizophrenic patients. METHOD:
      Thirty-one patients with schizophrenia and comorbid alcohol abuse or dependence
      were treated for 12 weeks in an outpatient study using naltrexone or placebo in a
      randomized, double-blind fashion in addition to their neuroleptic medication.
      Patients also participated in a weekly therapy using cognitive-behavioral drug
      relapse prevention strategies combined with skills training. Outcomes included
      drinking measured by the time line follow-back method, craving using the Tiffany
      Craving Questionnaire, psychotic symptoms using the Positive and Negative
      Symptoms Scale (PANSS), side effects and a measures of abnormal involuntary
      movements. RESULTS: There were no significant differences in treatment exposure
      or medication compliance between groups. Naltrexone treated patients had
      significantly fewer drinking days, heavy drinking days (>5 drinks) and reported
      less craving compared to the placebo treated patients. Naltrexone did not affect
      symptoms of schizophrenia, such as psychosis. The medication was well tolerated
      and there were no group differences in side effects. CONCLUSIONS: These data
      suggest that naltrexone may be an effective medication for individuals with
      comorbid alcohol dependence and schizophrenia. Given the widespread problems
      associated with alcohol misuse in this population, and the lack of effective
      pharmacotherapies, these findings represent an exciting clinical development.

PMID- 14634718
TI  - Editorial note: MDMA-induced dopamine neurotoxicity.

PMID- 14634717
TI  - Immunocytochemical study of the forebrain serotonergic innervation in Sardinian
      alcohol-preferring rats.
AB  - RATIONALE: The anxiolytic effect of ethanol is generally considered to be
      causally related to the development of alcohol dependence, and serotonin (5-HT)
      has been involved in both alcohol abuse and anxiety disorders. Several lines of
      evidence suggest an inverse relationship between alcohol abuse and central
      serotonergic neurotransmission. OBJECTIVES: When tested in the elevated plus
      maze, selectively bred Sardinian alcohol-preferring (sP) rats display a higher
      degree of anxiety than Sardinian alcohol-non-preferring rats (sNP); this behavior
      is reversed by voluntary ethanol intake. The present study examined whether sP
      rats differed with respect to the 5-HT innervation in different forebrain areas.
      METHODS: We performed an immunohistochemistry study using an antibody raised
      against serotonin transporter (SERT), a marker for 5-HT fibers, coupled with an
      unbiased stereology, the method used to count the number of 5-HT neurons in the
      raphe nuclei. RESULTS: The SERT-positive innervation density was found to be
      significantly lower in the medial-prefrontal cortex and in the shell of the
      nucleus accumbens of the ethanol-naive sP rats (sP-N) when compared with the sNP
      and unselected Wistar rats. No differences were found in the caudate putamen and
      hippocampus. The stereological analysis showed a significant difference in the
      number of 5-HT neurons in the dorsal but not in the median raphe of sP-N rats,
      compared with sNP and Wistar rats. Analysis of the cell body cross-sectional area
      revealed no differences among the three lines of rats either in the dorsal or in
      the median raphe. In sP rats that had voluntarily drunk ethanol for 14
      consecutive days (sP-exp), no differences were found in the 5-HT innervation
      relative to sP-N animals. CONCLUSIONS: These results indicate a selective
      reduction of innervation in the medial portion of the mesocorticolimbic 5-HT
      system in sP rats, suggesting that this genetically determined difference may be
      involved in the contrasting alcohol preference and consumption of sP and sNP
      animals.

PMID- 14634719
TI  - Dependency of sugar transport and phosphorylation by the phosphoenolpyruvate
      dependent phosphotransferase system on membranous phosphatidylethanolamine in
      Escherichia coli: studies with a pssA mutant lacking phosphatidylserine synthase.
AB  - An isogenic pair of Escherichia coli strains lacking ( pssA) and possessing (wild
      type) the enzyme phosphatidylserine synthase was used to estimate the effects of
      the total lack of phosphatidylethanolamine (PE), the major phospholipid in E.
      coli membranes, on the activities of several sugar permeases (enzymes II) of the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS). The mutant exhibits
      greatly elevated levels of phosphatidylglycerol (PG), a lipid that has been
      reported to stimulate the in vitro activities of several PTS permeases. The
      activities, thermal stabilities, and detergent sensitivities of three PTS
      permeases, the glucose enzyme II (II(Glc)), the mannose enzyme II (II(Man)) and
      the mannitol enzyme II (II(Mtl)), were characterized. Western blot analyses
      revealed that the protein levels of II(Glc) were not appreciably altered by the
      loss of PE. In the pssA mutant, II(Glc) and II(Man) activities were depressed
      both in vivo and in vitro, with the in vivo transport activities being depressed
      much more than the in vitro phosphorylation activities. II(Mtl) also exhibited
      depressed transport activity in vivo but showed normal phosphorylation activities
      in vitro. II(Man) and II(Glc) exhibited greater thermal lability in the pssA
      mutant membranes than in the wild-type membranes, but II(Mtl) showed enhanced
      thermal stability. All three enzymes were activated by exposure to TritonX100
      (0.4%) or deoxycholate (0.2%) and inhibited by SDS (0.1%), but II(Mtl) was the
      least affected. II(Man) and, to a lesser degree, II(Glc) were more sensitive to
      detergent treatments in the pssA mutant membranes than in the wild-type membranes
      while II(Mtl) showed no differential effect. The results suggest that all three
      PTS permeases exhibit strong phospholipid dependencies for transport activity in
      vivo but much weaker and differential dependencies for phosphorylation activities
      in vitro, with II(Man) exhibiting the greatest and II(Mtl) the least dependency.
      The effects of lipid composition on thermal sensitivities and detergent
      activation responses paralleled the effects on in vitro phosphorylation
      activities. These results together with those previously published suggest that,
      while the in vivo transport activities of all PTS enzymes II require an
      appropriate anionic to zwitterionic phospholipid balance, the in vitro
      phosphorylation activities of these same enzymes show much weaker and
      differential dependencies. Alteration of the phospholipid composition of the
      membrane thus allows functional dissection of transport from the phosphorylation
      activities of PTS enzyme complexes.

PMID- 14634720
TI  - The reliability of isokinetic testing of the ankle joint and a heel-raise test
      for endurance.
AB  - The aim of the present study was to investigate the reliability of different
      methods used for isokinetic testing of calf muscle strength and endurance. The
      detailed evaluation of test-retest reliability serves the purpose of establishing
      reliable research tools when evaluating patients who have sustained an Achilles
      tendon rupture. The test-retest reliability of isokinetic measurements at the
      ankle for eccentric and concentric muscle action was calculated in ten healthy
      male volunteers using intra-class correlation (ICC) and coefficient of variation
      (CV). Three different positions were compared at the angular velocities of 30
      degrees /s and 180 degrees /s for right and left ankles. The ICC for plantar
      flexion was 0.37-0.95, whilst it was 0.00-0.96 for dorsiflexion. The
      corresponding CVs were 4.0-19.9 and 2.4-19.8 respectively. The test-retest
      reliability of standardised heel-raises, Achilles tendon width, calf
      circumference and ankle range of motion revealed ICC values of 0.71-0.98 and CVs
      of 0.67-19.1. The test-retest interval was 5 to 7 days. We conclude that all
      three positions studied for the isokinetic evaluation of calf muscle function are
      equally reliable concerning plantar flexion at the ankle joint. The same level of
      reliability was also found in the evaluation of the standing heel-raise test and
      the isokinetic dorsiflexion test, except for dorsiflexion in the supine position.
      The reliability of the investigated methods was only fair despite the use of a
      detailed and standardised test protocol.

PMID- 14634721
TI  - An anatomical study of the meniscofibular ligament.
AB  - We examined the anatomical structure of a ligament (ligamentum meniscofibulare)
      between apex fibulae and lateral meniscus by macroscopic and microscopic
      dissection and transillumination method in 50 knees of 25 cadavers (5 were
      fresh). We analyzed the function of this ligament, which runs between the head of
      the fibulae and lateral meniscus. The existence of a connection between knee
      joint and proximal tibiofibular joint was demonstrated by injecting colored
      liquid into the knee joint space and transillumination. The mensicofibular
      ligament is a capsular ligament originating from the lateral meniscus that is
      anterior to the popliteal muscle tendon. The meniscofibular ligament, which is
      attached to fibula with rotatory motion at one end and to the lateral meniscus at
      the other, is believed to position the lateral meniscus and therefore to play a
      key role in the knee joint.

PMID- 14634722
TI  - The effect of cyclosporin A on the level of big endothelin in patients one year
      after orthotopic heart transplantation.
AB  - Orthotopic heart transplantation (OHTx) is currently an established method for
      the treatment of end-stage heart failure. Persistent elevated plasma endothelin-1
      (ET-1) levels have been reported after successful OHTx, the etiology of which is
      not yet fully understood. Immunosuppressive therapy is assumed to be one of the
      possible factors affecting ET-1 levels in the body. The present study evaluated
      the effect of cyclosporin A (CyA) on big ET-1 levels (a precursor of ET-1) in
      patients 1 year after successful OHTx. The study population comprised 34 patients
      after OHTx (28 males, 6 females, mean age 49.56+/-11.83 years) divided into two
      groups according to immunosuppressive protocol (17 patients on cyclosporine
      azathioprine-prednisone and 17 patients on cyclosporine-mycophenolate mofetil
      prednisone therapy). Plasma levels of big ET-1 and CyA were available for all
      patients. The control groups consisted of 10 healthy individuals (8 males, 2
      females, mean age 41.1+/-11.55 years) and 20 patients with severe heart failure
      (15 males, 5 females, mean age 54.45+/-8.49 years), respectively. Big ET-1 plasma
      levels were found to be elevated in OHTx patients in comparison with healthy
      controls (13.63+/-11.3 fmol/ml vs 2.99+/-1.98 fmol/ml, P=0.005). Big ET-1 plasma
      levels correlated with plasma CyA levels in patients treated with cyclosporine
      azathioprine-prednisone ( r=0.53, P=0.03). This was not the case in either in the
      OHTx patients as a whole or in the subgroup of patients on cyclosporine
      mycophenolate mofetil-prednisone therapy. The plasma levels of big ET-1 are
      dependent on CyA plasma levels 1 year after successful OHTx in patients treated
      with the immunosuppressive combination of cyclosporine, azathioprine, and
      prednisone. As this finding was not observed in the mycophenolate group of
      patients, mycophenolate mofetil might affect the alteration of the endothelin
      metabolism.

PMID- 14634723
TI  - Tissue Doppler imaging estimation of pulmonary artery occlusion pressure in ICU
      patients.
AB  - OBJECTIVE: Earlier reports suggested that transthoracic (TTE) determination of
      the ratio of mitral inflow E wave velocity to early diastolic mitral annulus
      velocity (E/E') measured by tissue Doppler imaging (TDI) closely approximates
      PAOP in cardiac patients. However, the value of E/E' for PAOP assessment in ICU
      patients has not been evaluated. This study assessed whether the E/E' ratio
      provides an accurate estimation of pulmonary artery occlusion pressure (PAOP) in
      mechanically ventilated ICU patients. DESIGN AND SETTING: Prospective, open,
      clinical study in the ICU of a university hospital. PATIENTS: Twenty-three
      consecutive mechanically ventilated patients. INTERVENTIONS: Volume expansion in
      14 patients. MEASUREMENTS AND RESULTS: Doppler TTE or TEE mitral inflow and TDI
      mitral annulus velocities were determined and compared with PAOP measured using a
      Swan-Ganz catheter. Of all the Doppler variables studied the best correlations
      were observed between PAOP and the lateral (r=0.84) and medial (r=0.76) annulus
      E/E' ratio and remained highly significant when the analysis was restricted to
      TEE (r=0.91 and 0.86) or TTE (r=0.73 and 0.61). The sensitivities and
      specificities of estimating PAOP at 15 mmHg or higher were, respectively, 86% and
      81% for lateral E/E' above 7.5 and 76% and 80% for medial E/E' above 9. PAOP
      changes after volume expansion (700+/-230 ml) were limited and accurately
      assessed by repeated E/E' determinations. CONCLUSIONS: In mechanically ventilated
      ICU patients TTE or TEE E/E' determinations using TDI closely approximate PAOP.

PMID- 14634724
TI  - 'Treat first, ask later?' Emergency research in acute neurology and
      neurotraumatology in the European Union.

PMID- 14634725
TI  - Protein losing enteropathy in critically ill adult patients with burns: a
      preliminary report.
AB  - OBJECTIVE: Few data have been published regarding protein losing enteropathy in
      adult patients with burns. This study characterised the presence of protein
      losing enteropathy in adults with burns and examined the relationship between the
      magnitude of burn size and the severity of protein loss. METHODS: Twenty adult
      patients with burns (BSA 31+/-25%, range 2-80%) were studied. Fluid resuscitation
      was based on the Parkland's formula. Protein loss into the gastrointestinal tract
      was measured using faecal alpha1-antitrypsin (FA-1-AT) concentrations. Serial
      measurements of serum protein and albumin concentrations were performed. RESULTS:
      Fourteen patients demonstrated elevations in FA-1-AT levels. The mean peak FA-1
      AT level was 3.6+/-4.2 mg/g dry weight of stool. Two patients demonstrated
      elevated FA-1-AT excretion 1.5 months and 3 months after the burns. There was a
      good correlation between burn size and FA-1-AT excretion (R2=0.40). CONCLUSIONS:
      Protein losing enteropathy was demonstrable in patients with major burns. The
      magnitude of this phenomenon appears to be proportional to the burns size.

PMID- 14634726
TI  - Compartmentalisation of cytokines and cytokine inhibitors in ventilator
      associated pneumonia.
AB  - OBJECTIVE: To examine whether cytokine concentrations change in the pulmonary
      compartment during the development of ventilator-associated pneumonia (VAP).
      DESIGN: Non-directed bronchial lavage (NBL) was performed every 48 h in
      critically ill mechanically ventilated patients. Serial measurements of the
      cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta,
      IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I
      (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II
      (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA.
      SETTING: An adult medical and surgical university hospital intensive care unit.
      PATIENTS: Nine patients who developed VAP and nineteen patients who did not
      develop VAP served as controls. INTERVENTIONS: None. RESULTS: Plasma
      concentrations of the measured cytokines and cytokine inhibitors did not change
      significantly in any patients. In control patients, NBL fluid concentrations of
      sIL-1RII decreased significantly over time (P=0.01). In patients who developed
      VAP, NBL fluid concentrations of TNFalpha, sTNFalphaRI, IL-1alpha, and IL-1beta
      increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively).
      Furthermore, NBL fluid/plasma concentration ratios for TNFalpha, sTNFalphaRI, IL
      1alpha, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001,
      P=0.001, P=0.04, P=0.03, and P=0.04, respectively). CONCLUSION: Our results
      suggest that the production of important cytokines and cytokine inhibitors is
      compartmentalised within the lung in critically ill mechanically ventilated
      patients who develop VAP.

PMID- 14634727
TI  - Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic
      acids in gestational diabetes.
AB  - AIMS/HYPOTHESIS: Gestational diabetes is a metabolic disorder affecting 2-5% of
      women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular
      disease. Insulin resistance, a characteristic of gestational diabetes and
      obesity, is correlated with the fatty acids profile of the red cell and skeletal
      muscle membranes. We investigated the plasma and red cell fatty acid status of
      gestational diabetes. The effect of obesity on membrane fatty acids was also
      examined. METHODS: Fasting blood obtained at diagnosis was analysed for the fatty
      acids in plasma choline phosphoglycerides and red cell choline and ethanolamine
      phosphoglycerides. RESULTS: There were reductions in arachidonic acid (controls
      10.74+/-2.35 vs gestational diabetes 8.35+/-3.49, p<0.01) and docosahexaenoic
      acid (controls 6.31+/-2.67 vs gestational diabetes 3.25+/-2.00, p<0.0001) in the
      red cell choline phosphoglycerides in gestational diabetes. A similar pattern was
      found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and
      docosahexaenoic acids depletion in the red cell choline phosphoglycerides was
      much greater in overweight/obese gestational diabetes (arachidonic acid=7.49+/
      3.37, docosahexaenoic acid=2.98+/-2.18, p<0.01) compared with lean gestational
      diabetes (arachidonic acid=10.03+/-2.74, docosahexaenoic acid=4.18+/-1.42).
      CONCLUSION/INTERPRETATION: Apparently normal plasma choline phosphoglycerides
      fatty acids profile in the gestational diabetic women suggested that membrane
      lipid abnormality is associated specifically with perturbation in the membrane.
      The fact that the lipid abnormality is more pronounced in the outer leaflet of
      the membrane where most of receptor binding and enzyme activities take place
      might provide an explanation for the increased insulin resistance in gestational
      diabetes and obesity.

PMID- 14634728
TI  - Synteny between a major heading-date QTL in perennial ryegrass (Lolium perenne
      L.) and the Hd3 heading-date locus in rice.
AB  - The genetic control of induction to flowering has been studied extensively in
      both model and crop species because of its fundamental biological and economic
      significance. An ultimate aim of many of these studies has been the application
      of the understanding of control of flowering that can be gained from the study of
      model species, to the improvement of crop species. The present study identifies a
      region of genetic synteny between rice and Lolium perenne, which contains the Hd3
      heading-date QTL in rice and a major QTL, accounting for up to 70% of the
      variance associated with heading date in L. perenne. The identification of
      synteny between rice and L. perenne in this region demonstrates the direct
      applicability of the rice genome to the understanding of biological processes in
      other species. Specifically, this syntenic relationship will greatly facilitate
      the genetic dissection of aspects of heading-date induction by enabling the
      magnitude of the genetic component of the heading-date QTL in L. perenne to be
      combined with the sequencing and annotation information from the rice genome.

PMID- 14634729
TI  - Comparative analysis of chloroplast DNA variability in wild and cultivated
      Citrullus species.
AB  - PCR amplification and restriction site analysis of chloroplast (cp) DNA regions
      was used to detect inter- and intraspecific differences in the genus Citrullus.
      More than 55 C. lanatus and 15 C. colocynthis accessions collected from diverse
      geographical areas, C. ecirrhosus and C. rehmii were used. Most of the cpDNA
      variation within Citrullus was the result of large indels and transitions and
      transversions. Indels at the ndhA, trnS- trnfM and trnC- trnD regions and several
      substitutions at restriction enzyme sites can be used to separate C. colocynthis
      from the other Citrullus species. A nucleotide substitution at a restriction
      enzyme site at the 3' flanking region of ndhF provided a diagnostic haplotype for
      C. lanatus var. lanatus, the cultivated watermelon. Similarly, a nucleotide
      substitution at an intergenic spacer region of the trnC- trnD region resulted in
      a diagnostic haplotype for citron, C. lanatus var. citroides. Several C. lanatus
      var. citroides accessions showed the var. lanatus haplotype. C. rehmii showed
      almost the same haplotype as C. lanatus var. citroides with the exception of a
      unique insertion at a cpSSR site. Since C. ecirrhosus lacks the derived
      diagnostic nucleotide substitutions of C. lanatus, it is probably the progenitor
      of the cultivated watermelon. Intraspecific haplotypes detected within C.
      colocynthis were associated with geographic origin.

PMID- 14634732
TI  - [Precision of navigation-assisted surgery of the thoracic and lumbar spine].
AB  - The goal of these studies was to evaluate the accuracy of in vivo and in vitro
      application of CT- and C-arm-based navigation at the thoracic and lumbar spine.
      With CT based navigation, 82 pedicle screws were consecutively inserted, 53 into
      the thoracic and 29 into the lumbar spine. Seven (13%) perforations were detected
      at the thoracic spine and two (7%) at the lumbar spine. Additionally, minor
      perforations below the thread depth were seen in six (11%) thoracic and in two
      (7%) lumbar instrumentation. With C-arm-based navigation, 74 screws were
      consecutively placed into 38 thoracic and 36 lumbar pedicles. Perforations were
      noted in ten (26%) thoracic and four (11%) lumbar implants. Minor perforations
      were observed in another nine (24%) thoracic and ten (28%) lumbar pedicles. The
      observer-independent and standardized in vitro study based on a transpedicular
      3.2-mm drill hole aiming a 4-mm steel ball in a plastic bone model showed pedicle
      perforations of the drill canal only in thoracic vertebrae, 1 of 15 in CT-based
      and 3 of 15 in C-arm navigation. The quantitative calculation of the smallest
      distance between the central line through the drill canal and the center of the
      steel ball resulted in 1.4 mm (0.5-4.8 mm) for the CT-based navigation at the
      thoracic spine and in 1.8 mm (0.5-3 mm) at the lumbar spine. For the C-arm based
      navigation the distance was 2.6 mm (0.9-4.8 mm) for the thoracic spine and 2 mm
      (1.2-3 mm) for the lumbar spine. In our opinion, the clinical results of the
      comparative accuracy of CT- and C-arm-based navigation in the present study
      showed moderate advantages of the CT-based technique in the thoracic spine,
      whereas CT- and C-arm based navigation had comparable perforation rates at the
      lumbar pedicle. The results of the experimental study correlated with the
      clinical data.

PMID- 14634733
TI  - [Iso-C(3D0-assisted) navigated implantation of pedicle screws in thoracic lumbar
      vertebrae].
AB  - The mobile Siremobil Iso-C(3D) C-arm (Siemens AG, Medical Solutions, Erlangen) is
      the first device that permits the intraoperative three-dimensional (3D)
      representation of bone structures. A high-resolution isotropic 3D data cube in
      the isocenter with an edge length of approximately 12 cm is calculated
      simultaneously. The Siremobil Iso-C(3D) is linked to navigation with the
      integrated NaviLink interface (Siemens AG, Medical Solutions, Erlangen). This
      makes it possible to transfer the generated 3D data directly to the linked
      navigation system Surgigate (Medivision, Oberndorf, Switzerland). In this
      prospective clinical trial we evaluated the accuracy of pedicle screw placement
      using the Siremobil Iso-C(3D) C-arm. The results were compared to the
      conventional approach and other computer-assisted procedures (CT-based
      navigation, C-arm-based 2D navigation) in historical control groups. A total of
      141 pedicle screws were placed in 30 patients (70 thoracic spine, 71 lumbar
      spine). Only in one single case was misplacement shown in the postoperative
      control CT scan (0.71%), the lowest rate of incorrect placements of all
      techniques. Also the lowest average fluoroscopy time (1.28+/-0.56 min) was
      achieved during the placement of pedicle screws on the spine with Iso-C(3D)
      navigation at a comparable average OR duration (103.26+/-23.3 min). There were no
      postoperative neurological complications in all 30 patients. From these data we
      conclude that Iso-C(3D) navigation of pedicle screws is a very accurate method in
      the correct placement of pedicle screws.

PMID- 14634734
TI  - [CT and fluoroscopy based navigation in pelvic surgery].
AB  - Navigation procedures based upon CT data were introduced into spine surgery in
      1994. Since then the method has been used in other areas, such as joint
      replacement, reconstructive surgery and tumor surgery, because of its high
      precision and reduced radiation exposure. The original CT-based spine module can
      be adapted for pelvic surgery with the prerequisite, that the positioning of the
      fragments is identical in CT and at operation; otherwise, a new data set has to
      be acquired. The experience with CT-based navigation in pelvic surgery will be
      explained in the context of five percutaneous screw fixations and three tumor
      resections. The technique will be described. The fluoroscopy-based navigation has
      been used in trauma surgery since the late 1990 s. Since than the method has
      gained wide acceptance in the field of joint replacement and reconstructive
      surgery as well. Between June 2000 and December 2002 we performed 36 percutaneous
      screw fixations in the pelvis with postoperative X-ray and CT control. Thirty
      five of the 36 screws were placed correctly. In one screw an anterior cortex
      perforation of the sacrum was seen on CT, but without neurological consequences.
      Based upon our clinical experience we believe that CT-based navigation is
      indicated in screw fixations for minimally displaced pelvic injuries or dysplasia
      and, with increasing importance, in tumor surgery. Fluoroscopy based navigation
      with adequate image quality is the method of choice for SI screw fixations in
      traumatic or degenerative instabilities, especially if an update of the images is
      needed.

PMID- 14634735
TI  - [Fluoroscopy based surgical navitation vs. mechanical guidance system for
      percutaneous interventions. A controlled prospective study exemplified by distal
      locking of intramedullary nails].
AB  - The aim of this study was to directly compare mechanically based targetting and
      surgical navigation when applied for percutaneous osteosynthesis. The distal
      locking procedure of intramedullary nails was used as the clinical model for a
      controlled prospective study. A total of 50 patients were included in two groups.
      In group 1, the distal locking was done with a mechanical aiming device while in
      group 2 this was done using a fluoroscopy based surgical navigation system. The
      target parameters were the precision attained, the necessary operation and
      fluoroscopy times as well as the number and severity of intra-operative problems.
      The drill-bit failed to pass through the interlocking hole in one patient with
      mechanical guidance and in two patients with surgical navigation. The average
      procedure time for distal locking with mechanical guidance was 6.9 minutes
      compared with 37.6 minutes with surgical navigation. An additional 44 minutes
      were required before skin incision and after skin closure as setup time for the
      navigation system. There was no significant difference in the fluoroscopy time or
      in the number of intra-operative technical problems. Surgical navigation
      increased the demand for resources but failed to improve the precision of distal
      locking compared with mechanical guidance. Further clinical studies are required
      to determine to what degree these results, using a special model, relate to other
      applications.

PMID- 14634736
TI  - [CT-free image guided acetabulum navigation in clinical routine].
AB  - After experimental and preclinical evaluation (HAP Paul Award 2001) of the CT
      free image-guided surgical navigation system for acetabular cup placement
      (SurgiGATE C-arm cup" by Medivision, Switzerland), the system was introduced into
      clinical routine. The computation of the angular orientation of the cup is based
      on reference coordinates from the anterior pelvic plane concept. A hybrid
      strategy for pelvic landmark acquisition has been introduced involving
      percutaneous pointer-based digitization with the noninvasive biplanar landmark
      reconstruction using multiple registered fluoroscopy images. From January 2001 to
      December 2002, a total of 256 consecutive patients with primary osteoarthrosis
      (mean age 69 years, 161 male, 95 female, 132 left, and 124 right hip joints) were
      operated on with the hybrid CT-free navigation system. During each operation the
      angular orientation of the inserted implant was recorded. To determine the
      placement accuracy of the acetabular components, 50 consecutive patients
      underwent a CT scan 7-10 days postoperatively to analyze the cup position related
      to the anterior pelvic plane. This was all done blinded by the same investigator
      with the planning software of the CT-based navigation system of Medivision. There
      was no significant learning curve observed for the use of the system. The mean
      value for postoperative inclination was 43 degrees (SD 3.0, range: 37 degrees -49
      degrees ) and for anteversion 19 degrees (SD 3.9, range: 10 degrees -28 degrees
      ). The resulting system accuracy, i.e., the difference between intraoperatively
      calculated cup orientation and postoperatively measured implant position showed a
      mean error of 1.5 degrees for the inclination (maximum 5 degrees, SD 1.1) and 2.4
      degrees for the anteversion (maximum 6 degrees, SD 1.3). An accuracy of better
      than 5 degrees inclination and 6 degrees anteversion was achieved under clinical
      conditions, which implies that there is no significant difference in performance
      from the established CT-based navigation methods. Image-guided CT-free cup
      navigation provides a reliable solution for future THA.

PMID- 14634737
TI  - [CT-based and CT-free navigation in knee prosthesis implantation. Results of a
      prospective study].
AB  - INTRODUCTION: Accurate leg alignment is one important factor for long-term
      survival in total knee arthroplasty (TKA). The classical surgeon-controlled
      technique is associated with a deviation of the leg axis of more than 3 degrees
      in up to 30% of cases, regardless of the surgeon's experience. The aim of this
      study was to test the efficiency of a CT-based and CT-free navigation system in
      restoration of the leg axis. METHOD: 100 TKA (PFC-Sigma, DePuy) were implanted
      either using the CT-based or CT-free module of the Vector-Vision navigation
      System (BrainLAB). There were no significant differences between the groups in
      preoperative leg deformity. Accuracy of implantation was determined on
      postoperative long-leg coronal and lateral X-rays. RESULTS: A postoperative leg
      axis between 3 degrees varus and 3 degrees valgus was obtained in 46 patients
      (92%) in the CT-based group (A) and in 48 patients (96%) in the CT-free group
      (B). No significant differences were found for varus / valgus orientation (+/-3
      degrees ) of the femoral (A=96%; B=94%) and tibial (A and B each 98%) components.
      CONCLUSION: The use of the CT-based and CT-free Vector-Vision system allows a
      significant improvement in the accuracy of implantation in TKA. The CT-based
      module has the advantage of precise preoperative planning. On the other hand
      there are additional costs and time-consuming logistics. The advantages of the CT
      free module are the intraoperative visualisation of the leg axis, the ligament
      balancing and joint kinematics. Cutting errors can be detected and corrected with
      both modules.

PMID- 14634738
TI  - [CT analysis of leg alignment after conventional vs. navigated knee prosthesis
      implantation. Initial results of a controlled, prospective and randomized study].
AB  - INTRODUCTION: Correct alignment of the leg is one of the significant factors for
      the outcome after TKA. Previous studies have shown that the use of a navigation
      system can improve the alignment. However, for the positioning of the femoral
      component no validated data are available. This article presents the first
      results of a controlled, prospective and randomised trial comparing navigation
      versus free-hand implantation in TKA with special reference to the rotation of
      the femoral component. METHODS: Since January 2003, all patients with primary
      arthrosis of the knee admitted to our hospital for TKA have been followed
      prospectively. For this first analysis, data were collected over a period of 5
      months. Apart from the usual clinical evaluations, all patients had CT of the leg
      prior to the operation and 1 week postoperatively. Measurement of axis and
      rotation was performed by staff members of the X-ray department who had no
      knowledge of the operation technique (navigation vs. free-hand). RESULTS: Twenty
      five sets of CT scans have been analysed, from 12 navigated operations and 13
      freehand procedures. All 12 of the navigated knees were within the interval of +/
      3 degrees varus/valgus deviation, but only 8 of the 13 non-navigated knees met
      this criteria. The analysis of the rotation position of the femoral component
      revealed no difference between the two groups. CONCLUSION: By using an
      intraoperative navigation system, the accuracy of the alignment in TKA can be
      improved. Long-term studies will have to be carried out to verify whether this
      will lead to a lasting benefit for the patient. Concerning the rotation position
      of the femoral implant, no conclusion can be made regarding the recommended
      rotation position at this point of the study.

PMID- 14634739
TI  - [Navigation of tumors and metastases in the area of the thoraco-lumbar spine].
AB  - In this clinical feasibility study, CT-based verification of the efficacy of
      navigated decompression and pedicle screw placement in patients who had tumor
      related posterior surgery was demonstrated. Eighty-six percent of the pedicle
      screws were positioned centrally in the bone without perforation; in all patients
      accurate decompression was seen. The accuracy of transpedicle screw implantation
      postoperatively was investigated with CT. In contrast to other published studies,
      no postoperative neurologic deterioration was seen in the patients as a result of
      using computer-aided surgical procedures. At the same time we were able to
      achieve complete decompression of the neural structures for radiologic and
      neurologic findings. Because of inaccurate registration, it was not possible to
      use computer-aided implantation surgery for 15% of the pedicles and, therefore, a
      conventional fluoroscopic approach was used. Our initial results indicate that
      computer-aided frameless navigation of tumor surgery of the spine is a safe
      technique which improves surgical performance during posterior decompression and
      transpedicle stabilization. In addition, CAS surgery improved the intraoperative
      information about the tumor and the current surgical intervention during
      decompression. Nevertheless the technique should be used only by experienced
      surgeons who can, if required, continue the operation using conventional
      techniques. Furthermore, the surgeon should have a complete theoretical
      understanding of the navigation system to minimize possible misinterpretation of
      computer guidance information.

PMID- 14634741
TI  - [Navigated Iso-C(3D)-based drilling of a osteochondral lesion of the talus].
AB  - Retrograde drilling of osteochondral lesions has obtained acceptable results in
      the initial stage. Intraoperatively not all lesions are accessible with the
      arthroscopic technique, despite being readily identifiable with modern imaging
      preoperatively. As an alternative, open surgical treatment is recommended to
      achieve good results. The use of computer-assisted navigated retrograde drilling
      of osteochondral lesions has been described with promising results as a new
      technique. Computed tomography (CT)- and fluoroscopy-based navigation systems in
      current use are limited in their flexibility. The drawbacks of fluoroscopy are
      lack of three-dimensional imaging intraoperatively. CT-based navigation still
      requires intraoperative cumbersome registration, extra preoperative planning, and
      imaging with further technical resources. In the current case report, we describe
      a patient with an osteochondral lesion of the posteromedial talus. In addition to
      the current method of arthroscopic evaluation and treatment, we also introduce an
      alternative technique of using Iso-C(3D)-based navigation-assisted retrograde
      drilling of the lesion. The advantages of this technique are an actual
      intraoperative three-dimensional imaging for the use of navigation without the
      need for anatomical registration and an immediate postoperative control of
      surgical treatment. The results of this case report demonstrate accurately
      navigated drilling with the described system. The accuracy was confirmed with
      immediate intraoperative Iso-C(3D) and postoperative CT scans. Our results
      indicate that the use of an Iso-C(3D) navigation system is a possible alternative
      to arthroscopic or open drilling for osteochondral lesions of the talus. To
      provide further evidence for the use of Iso-C (3D)-based drilling, current
      studies will start at our institution.

PMID- 14634740
TI  - [Integration of modern technologies in therapy of sarcomas of the pelvis.
      Computer-assisted hemipelvectomy and implantation of a "custom-made" Bonit
      gentamycin coated partial pelvic prosthesis].
AB  - The resection of primary malignancies in the pelvis is technically demanding as
      organs and structures are to be preserved and reconstruction of the defect as
      well as the postoperative function and rehabilitation are dependent on an optimal
      prosthesis. We present two patients with a sarcoma of the pelvis where for the
      first time a structured concept of technology integration led to a press-fit
      implantation of a hemipelvic prosthesis. This concept includes the design and
      production of a "custom-made" prosthesis as a hemipelvic substitute and the
      coating of this prosthesis with Bonit, a second-generation calcium phosphate, and
      gentamycin in watery solution. The tumor resection was done with computer
      assisted surgery based on computed tomographies (CT) of the pelvis model done by
      rapid prototyping rather than on the CT of the patients' pelvis. With this
      procedure the presurgically simulated resection could be executed precisely with
      complete resection of the tumors and an accuracy which allowed an exact
      implantation of the prosthesis. The course was uneventful with primary healing
      and no sign of an infection or loosening after 6 months.

PMID- 14634742
TI  - [Navigated reposition of transverse acetabulum fractures. A precision analysis].
AB  - Up to now navigated reduction control based on computed tomography (CT) image
      data could not be used commercially. With newly developed software, a transverse
      fracture of the acetabulum was reduced with navigation control in a laboratory
      test. The results were compared to visual and tactile control in a foam pelvis
      and specimen. Measurements were done with another magnet-based navigation system.
      The residual dislocation was measured with translation (mm) and rotation
      (degrees). Compared with visually controlled reduction, navigated reduction led
      to a residual dislocation of 0.7 mm and 0.9 degrees. Navigated reduction based on
      CT image data is also accurate for reduction of joint fractures under laboratory
      conditions. Further improvements of the software are planned for later in vivo
      use.

PMID- 14634743
TI  - [Navigated osteosynthesis of the proximal femur. An experimental study].
AB  - Screw position in femoral head has been considered the most important predictive
      factor for mechanical failure in pertrochanteric osteosynthesis, and correct
      positioning is assisted by fluoroscopic control. Although fluoroscopy leads to
      precise and reproducible results, it is associated with scattered radiation to
      the patient and surgical staff. Computer-assisted surgery (CAS) may be an
      alternative in means of achieving precise screw insertion with a low radiation
      dose. We designed a laboratory study in which artificial proximal femora were
      submitted to insertions of a dynamic hip screw (DHS) and an anti-rotational screw
      (ARS). Three set-ups were tested: (1) conventional implantation with two
      simultaneous C-arms using a guide wire; (2) drilling and implantation controlled
      by CAS solely with a 3.2-mm drill bit, then insertion of a guide wire and
      drilling for the dynamic hip screw; (3) after navigated drilling (3.2 mm) a
      fluoroscopic control was performed. Five variables were used comparing methods
      and surgeons: operation time, radiation time, tip-apex distance (TAD), and the
      insertion neck-shaft angles of DHS and ARS. Considering TAD as a precision
      parameter, CAS led to screw insertion as accurate as with fluoroscopic control,
      with a reduction of radiation time up to 93%.

PMID- 14634744
TI  - [Prevention of skin cancer. Necessity, implementation and success].
AB  - Including malignant melanoma, basal cell carcinoma, and squamous cell carcinoma,
      skin cancer is the cancer with the highest incidence worldwide. Its incidence is
      increasing more rapidly than that of all other kinds of cancer. It is necessary
      to slow down this trend through preventive steps in order to reduce morbidity and
      mortality rates and to decrease the financial burden on the health systems. This
      goal could be achieved through primary (prevention of risk factors) and secondary
      prevention (early diagnosis and screening). This essay describes the necessity,
      realization, and success of these kinds of intervention programs. It especially
      portrays the procedures in Germany as they have been practiced for the last 15
      years by the Society of Dermatology Prevention and German Cancer Aid.

PMID- 14634745
TI  - [Cutaneous epithelial tumors. Molecular biology and pathogenesis-based therapy].
AB  - Basal cell carcinomas and squamous cell carcinomas are the most common human
      cancers and increasing in incidence. The development of novel, pathogenesis-based
      therapies requires a better knowledge of the molecular mechanisms leading to the
      development of these tumors. Basal cell carcinomas are characterized by aberrant
      activation of Sonic-Hedgehog (SHH) signaling due to mutations in the PTCH or SMOH
      genes. In addition, about 50% of the cases carry mutations in the TP53 tumor
      suppressor gene. Squamous cell carcinomas lack alterations of SHH signaling,
      while TP53 mutations are detectable in virtually all cases. Alterations in cell
      cycle regulatory genes, such as CDKN2A, are also common. Recently, specific
      inhibitors of the SHH-signaling pathway have been developed and shown promising
      results in preclinical studies on experimental basal cell carcinomas. However,
      the clinical significance of such targeted molecular therapy remains to be
      evaluated. Another successful pathogenesis-based therapy, which is already in
      clinical use, is the administration of topic immune response modifier imiquimod.
      This drug can eradicate non-melanoma skin cancers by different mechanisms,
      including cytokine-mediated stimulation of the anti-tumor immune response, as
      well as the induction of tumor cell apoptosis.

PMID- 14634746
TI  - [Merkel cell carcinoma. Clinical and histological differential diagnosis,
      diagnostic approach and therapy].
AB  - Merkel cell carcinomas are rare tumors of the skin with an aggressive behavior
      and frequent regional and distant metastases. Typically, the primary is a fast
      growing, painless, reddish nodule with an iceberg-like effect, broadening in the
      depth. On the trunk and the buttocks, deep clinically rather inconspicuous
      nodules can occur. The clinical differential diagnosis of the Merkel cell
      carcinoma includes skin metastases, malignant lymphomas, malignant adnexal tumors
      and cysts when the tumor is located deep in the soft tissue (e.g. on the
      buttocks). Histological and immunohistochemical analysis is necessary for the
      diagnosis. The demonstration of cytokeratin 20 in the typical globular
      distribution pattern is of main importance in the diagnosis of Merkel cell
      carcinoma. Because they are very rare, Merkel cell carcinomas are infrequently
      diagnosed clinically, in spite of the rather characteristic picture. Diagnostic
      excision with a safety margin of 3 cm is recommended followed by an adjuvant
      radiotherapy. The radiation field should include the area of the draining vessels
      and the first regional lymph nodes. There are some reports concerning the
      advantage of sentinel lymph node biopsy. In distant metastases, the therapy is
      multimodal and palliative including surgery, radiation and chemotherapy. Because
      of the high incidence of regional and distant metastases, regular follow-up is
      important.

PMID- 14634747
TI  - [Standard and experimental therapy of cutaneous T-cell lymphoma].
AB  - Cutaneous T-cell lymphoma represent a heterogeneous group of diseases
      characterized by skin invasion of monoclonal T-lymphocytes. These cutaneous T
      cell lymphomas are divided into 3 groups based on clinical, histological and
      immunohistological characteristics: Indolent with a survival time of over 10
      years, aggressive with a survival time less than 10 years and provisional (EORTC
      classification). Standard treatments such as PUVA, total skin electron beam,
      methotrexate, polychemotherapy regimens, retinoids and photopheresis have been
      used for years. Bexarotene is a newly registered drug. To achieve better response
      rates, several new drugs are being evaluated in clinical trails, including
      imiquimod, denileukon-diftitox, liposomal doxorubicin, adeno-interferon-gamma and
      various combination approaches.

PMID- 14634748
TI  - [Autologous fat grafting].
AB  - Autologous fat grafting is a standard method for soft tissue augmentation. The
      method is commonly used for volume restoration of the ageing face. Furthermore,
      atrophic scars, lipodystrophy and scleroderma en coup de sabre can be treated.
      Following liposuction, the harvested fat can be reinjected immediately or stored
      at minus 28 degrees C for at least 2 years. In most cases, several injections at
      3 to 4 months intervals are needed for good long-term effects. The procedure is
      used world-wide with good results and a minimum of side effects.

PMID- 14634749
TI  - [Molecular genetic mutation analysis of the PTPN11 gene in the multiple
      lentigines (LEOPARD) syndrome].
AB  - BACKGROUND AND OBJECTIVE: LEOPARD syndrome (MIM #151100) is a rare autosomal
      dominant condition with characteristic skin anomalies, facial dysmorphism,
      hypertelorism, cardiac anomalies, and occasional conductive hearing loss.
      Mutations in the PTPN11 gene are described as the causal gene defect for the
      clinical features of Noonan syndrome (MIM #163950), but also for LEOPARD
      syndrome. For confirmation of the clinical diagnosis of multiple lentigines
      syndrome, the molecular genetic mutation analysis in the PTPN11 gene could be
      helpful. PATIENTS/METHODS: We report on a family with LEOPARD syndrome in which
      the mutation analysis in the father and his daughter in the PTPN11 gene was
      carried out us:ng PCR, DHPLC, and automated sequencing. RESULTS: We could
      identify both father and daughter as carriers of the mutation Y279C in the PTPN11
      gene, which is known as a disease-related mutation. CONCLUSIONS: The allelic
      affinity to Noonan syndrome could thus be further supported.

PMID- 14634750
TI  - [Successful topical treatment of cutaneous sarcoidosis with tacrolimus].
AB  - A 56-year old female patient with cutaneous sarcoidosis in the face was treated
      with fumaric acid esters and doxycycline without any effect. Topical tacrolimus
      led clinically and histologically to a nearly complete remission within three
      months, which continued after 4 months of follow-up.

PMID- 14634751
TI  - [Comel-Netherton syndrome with bacterial superinfection].
AB  - A 10-year old boy, the child of unrelated Bosnian parents presented with a
      superinfected ichthyotic erythroderma. The clinical features, histological
      findings and hair analysis led to the diagnosis of the autosomal-recessive
      inherited Comel-Netherton syndrome witch bacterial superinfection. Under careful
      therapy with small amounts of topical tacrolimus (Protopic 0.1% ), he improved
      and had longer disease-free intervals. Tacrolimus was administered intermittently
      and not during acute flares, thus avoiding systemic resorption even after long
      time treatment despite the disturbed epidermal barrier in Comel-Netherton
      syndrome. Staphylococcus aureus producing enterotoxin C was isolated during
      flares which were sometimes accompanied by marked bacterial superinfection. It is
      possible, that this super antigen is involved in the observed aggravation of
      disease. The topical therapy with tacrolimus is an easy, flexible therapeutic
      option for this rare genodermatosis.

PMID- 14634752
TI  - [Miracles in dermatology? An overview of miraculous cures of skin diseases in the
      Catholic Church].
AB  - Miracles which can be observed in different religions are often closely connected
      to medicine. These miraculous cures, considered to be inexplicable by medical
      science, have been documented in Christian religion and in occidental culture for
      more than 2000 years. These miraculous healings are also reported in the field of
      dermatology. The miraculous bulletins documented by the Catholic Church take
      their beginning in the Old Testament and extend to the miraculous cures of
      Lourdes in present time. We provide an overview of miraculous healings of skin
      diseases, whereby accounts documented in the Bible, reports during the Middle
      Ages, and cases documented throughout the last century are discussed. In view of
      modern medicine, most of the miraculous healings do not meet modern demands of
      science, but remain important as milestones in medical and religious history.

PMID- 14634753
TI  - [Recurring episodes of fever with oral aphthae, lymph node swelling and joint
      symptoms in a 9-year-old boy. Diagnosis: PFAPA syndrome (Marshall syndrome)].

PMID- 14634754
TI  - [Syphilis -- renaissance of a forgotten disease? A recommendation of the DSTDG
      for diagnosis and therapy].

PMID- 14634755
TI  - Regulation of Aurora-A kinase on the mitotic spindle.
AB  - The error-free segregation of duplicated chromosomes during cell division is
      essential for the maintenance of an intact genome. This process is brought about
      by a highly dynamic bipolar array of microtubules, the mitotic spindle. The
      formation and function of the mitotic spindle during M-phase of the cell cycle is
      regulated by protein phosphorylation, involving multiple protein kinases and
      phosphatases. Prominent among the enzymes implicated in spindle assembly is the
      serine/threonine-specific protein kinase Aurora-A. In several common human
      tumors, Aurora-A is overexpressed, and deregulation of this kinase was shown to
      result in mitotic defects and aneuploidy. Moreover, recent genetic evidence
      directly links the human Aurora-A gene to cancer susceptibility. Several of the
      physiological substrates of Aurora-A presumably await identification, but recent
      studies are beginning to shed light on the regulation of this critical mitotic
      kinase. Here, we review these findings with particular emphasis on the role of
      TPX2, a prominent spindle component implicated in a Ran-GTP-mediated spindle
      assembly pathway.

PMID- 14634756
TI  - Inversion of the uterus at caesarean section.
AB  - INTRODUCTION: Inversion of the uterus through the uterine incision during
      caesarean section is a rare event. Therapy is usually simple and maternal
      morbidity is low when re-inversion of the uterus can be accomplished immediately.
      In cases of prolonged uterine inversion thereof, haemodynamic instability and
      shock, often out of proportion to the degree of blood loss, have been reported as
      serious sequelae. CASE REPORT: We describe such a case with a prolonged inversion
      to re-inversion interval where the patient suffered an intraoperative
      cardiovascular arrest during unrepositioned uterine inversion. Reposition of the
      uterus led to an immediate return of the patient's vital signs and improvement of
      her haemodynamic status. DISCUSSION: The mechanisms of haemodynamic instability
      and the technical aspects of manual reduction of the inverted, heavily contracted
      uterus during caesarean section are discussed.

PMID- 14634757
TI  - Gunshot injury of the proximal femoral physis.
AB  - A 12-year-old boy sustained a gunshot injury to the proximal femur. The bullet
      hole passed through the femoral neck very close to the proximal femoral physis
      (Ogden type 8 physeal injury) without neurovascular injury. The boy was treated
      conservatively with antibiotics and bedrest. Nine months later, avascular
      necrosis of the femoral head (Ratliff type 2) and limb shortening of 2 cm had
      developed. For this reason, a valgus intertrochanteric osteotomy was performed 1
      year after the injury. However, only partial revascularization of a necrotic
      femoral head segment occurred. For the residual necrotic segment in the weight
      bearing area and progressive shortening of the femur 3.5 years after injury, a
      valgus-extension intertrochanteric osteotomy was performed and remodelling of the
      necrotic fragment done. The boy is now over 19 years old. He has only minimal
      pain after sports activity and a slightly limited range of movement. The limb
      shortening is 1.5 cm.

PMID- 14634758
TI  - Anomalous alterations affecting microglia in the central nervous system of a
      fetus at 12 weeks of gestation: case report.
AB  - We report here on the first documented case of profound alterations specifically
      affecting the microglial population within the nervous system during the fetal
      period. This case, derived at gestational week 12, was one amongst a series of
      second trimester brains currently being investigated with respect to microglial
      colonization of the human fetal brain. No significant pathological alterations
      could be identified upon gross macroscopy or following microscopic analysis of
      serial brain sections stained with cresyl fast violet (Nissl). By contrast,
      sections stained immunohistochemically to detect MHC class II (CR3/43) and CD68
      (PG-M1) antigens revealed a marked pathological change in the morphology and
      density of microglia within the CNS. Specifically, labeled cells within the
      rostral telencephalon were clearly hypertrophied and emitted numerous, branched
      processes in all directions, appearing in an atypical 'hyper-ramified' state
      uncharacteristic of microglia found in normal brains at this age. However, cells
      located elsewhere in the CNS (for example in the thalamus and internal capsule)
      appeared in a less differentiated state (small, rounded cells lacking processes)
      when compared to those within normal age-matched control brains. The total
      density and distribution of these labeled cells far outnumbered that seen in
      normal development. As far as we are aware, such an anomaly specifically
      affecting microglia, has not been documented previously. Consequently, this case
      represents the first of its kind, and the remarkable observations outlined in
      this study bear considerable significance from a neuropathological standpoint for
      future investigations into pathological changes affecting microglia in the
      central nervous system during the fetal period.

PMID- 14634759
TI  - [Detection of coronary calcifications by electron beam tomography and multislice
      spiral CT: clinical relevance].
AB  - Coronary calcifications can be detected and quantified using electron beam
      tomography (EBT) or newer generation multi-slice spiral CT (MSCT) scanners. An
      abundance of data has been acquired by EBT. It could be shown that the amount of
      coronary calcium correlates to the coronary plaque burden. The detection of
      coronary calcium with CT imaging methods therefore provides a unique opportunity
      to detect and quantify coronary atherosclerosis in a subclinical stage.
      Consequently, the presence and amount of coronary calcium has been shown to be
      indicative for an increased coronary event risk in symptomatic and asymptomatic
      individuals. Several clinical studies found a predictive value that was superior
      to conventional risk factors. Clinically, the use of coronary calcification
      assessment may therefore be beneficial in patients who, based on traditional risk
      factors, seem to be at "intermediate risk" for coronary events (10-year event
      risk 10-20%) in order to decide on the aggressiveness of risk factor
      modification. The role of coronary calcium quantification to monitor the
      progression of disease has not been clarified yet. Large, ongoing trials will
      provide further data as to the relative merit of coronary calcium assessment for
      risk stratification and will help to more clearly define its clinical role. The
      relationship between coronary calcium and coronary stenoses is more complex.
      While the absence of coronary calcifications makes significant coronary stenoses
      unlikely, even large amounts of coronary calcium do not necessarily indicate the
      presence of coronary artery stenoses. Pronounced coronary calcifications as an
      isolated finding should therefore not be the motivation for invasive diagnostic
      procedures in the absence of other evidence of ischemic heart disease.

PMID- 14634760
TI  - [Phase III rehabilitation after heart transplantation].
AB  - INTRODUCTION: Longterm treatment after heart transplantation (HTX) improves
      survival, although the quality of life and exercise tolerance decreased
      continuously between one and ten years after transplantation. The role of
      physical exercise and psychological support in longterm treatment after HTX has
      not been determined. We analyzed the effects of a one year outpatient
      rehabilitation program in combination with a home based, computer assisted
      training program on exercise capacity, coronary risk factors and quality of life.
      METHODS: 20 heart transplant recipients in an intervention group and 12 patients
      after HTX in a control group participated in the study (IG (CG); 5.1+/-2.2 (4.5+/
      2.3) years after HTX; age: 55+/-7 (54+/-8) years; body mass index: 28.3+/-1.0
      (28.7+/-0.9) kg.m(-2)). Before and after the intervention, maximum and constant
      load exercise capacity, and self-reported quality of life were evaluated. The 12
      month intervention period included 10 days of exercise testing as well as medical
      and psychological support. Furthermore, the IG group performed a computer
      assisted and controlled home ergometer training every second day. RESULTS: After
      one year with 114+/-18 exercise training sessions, maximum oxygen consumption
      increased in the IG from 18.8+/-4.2 to 20.1+/-4.2 ml.min(-1).kg(-1) (p<0.05; CG
      19.3+/- 4.5 to 18.5+/-2.8 ml.min(- 1).kg(-1); p<0.01 IG vs CG). In the IG, lower
      back pain, body fat, and blood pressure were all reduced, while the self-reported
      quality of life, endurance exercise capacity and HDL cholesterol were increased.
      No significant changes occurred in the control group. CONCLUSIONS: When initiated
      years after heart transplantation, longterm rehabilitation reduced coronary risk
      factors and significantly improved both the subjects' quality of life, as well as
      a near to normal capacity for physical work.

PMID- 14634761
TI  - [Implantation of CardioWest total artificial heart in irreversible acute
      myocardial infarction shock-new hope for patients with infaust prognosis].
AB  - Patients in whom cardiogenic shock develops after acute myocardial infarction
      have a very high death rate despite early reperfusion therapy. Often hemodynamic
      stabilization can be achieved only by implantation of a mechanical circulatory
      support system. When pharmacological therapy and onset of percutaneous assist
      devices fails in cases representing expansive myocardial impairment without any
      chance of recovery, the indication for implanting a total artificial heart is
      given. We report on our first experiences with this extensive and innovative
      management of irreversible cardiogenic shock patients. In five patients (male,
      mean age 50 years) the CardioWest total artificial heart was implanted. All
      patients were in irreversible cardiogenic shock despite maximal dosages of
      catecholamines, intraaortic balloon pump and/or femorofemoral bypass. In all
      patients early reperfusion therapy was performed. After implantation of the
      CardioWest system, rapid recovery of all dysfunctional organ systems occurred in
      all patients. Four of five patients underwent successful heart transplantation
      after a mean support time of 156 days. One patient died because of enterocolic
      necroses caused by embolic event after termination of dicumarol therapy. In
      summary, first experiences justify this extensive management in these young
      patients who otherwise would have died within a few hours.

PMID- 14634762
TI  - [Neuropathological findings after cardiac surgery-retrospective study over 6
      years].
AB  - Neuropathological studies may contribute to the discovery of central nervous
      system complications after heart surgery and thus help to reduce the incidence of
      postoperative neurological or cognitive disturbances. We examined the brains of
      262 such patients operated for coronary bypass, valve replacement, or heart
      transplantation. Circulatory disturbances (macro- and microhemorrhages, infarcts,
      subarachnoid hemorrhages, and hypoxemic brain damage) were present in 128 cases
      (49%), as the cause of death in 33 cases (12.6%). The infarcts were caused by
      local arteriosclerosis of brain arteries, arterial emboli originating from the
      operative sites or myocardial infarctions, or by fat emboli, foreign body emboli
      or megakaryocytic capillary emboli in rare cases. Inflammatory disturbances were
      present in 17 cases and consisted of fungal or bacterial septicopyemic changes
      (12) or of glial nodules (5) as the substrate of a viral or autoimmunencephalitis
      (Bickerstaff). An incidental finding was Alzheimer's disease in 37 cases (14% of
      the material) of elderly patients, often associated with cerebral amyloid
      angiopathy but not as cause of death or cause of macroscopic brain hemorrhage.
      Since we have conducted an autopsy study, there is a limitation to transfer the
      documented changes to the total group of post-cardiac surgery patients with
      neurologic and cognitive deficits. Contrary to some previous reports,
      histologically overt microembolic phenomena do not seem to play a major role in
      our material. On the other hand, careful scrutiny revealed non-fatal white matter
      microhemorrhages of varying frequency in the different groups, especially after
      valve operations. These as well as the occasional glial nodules, after resorption
      and microscarring, could well be the cause of slight neurologic and cognitive
      impairments.

PMID- 14634763
TI  - [A xenogeneic acellularized matrix for heart valve tissue engineering: in vivo
      study in a sheep model].
AB  - BACKGROUND: The ideal scaffold material for tissue engineered heart valves is
      discussed controversially. We evaluated acellularized xenogenic matrix constructs
      with and without seeding with autologous vascular cells in the pulmonary
      circulation in a sheep model. METHODS: Porcine pulmonary valve conduits (n=16)
      were acellularized by trypsin/ EDTA incubation. Autologous myofibroblasts and
      endothelial cells were harvested from carotid arteries; xenogenic valve conduits
      (n=10) were repopulated with these autologous cells resulting in uniform cellular
      restitution of the pulmonary valve conduit surface. Using this method, we
      implanted autologous cell/xenogenic matrix constructs (XB) in ten animals. In six
      control animals acellularized/xenogenic matrix constructs (XA) were implanted. In
      each animal, cardiopulmonary bypass was used to resect the pulmonary valve and
      replace it with the xenogenic pulmonary valve conduits. The animals were killed
      after 6, 9 or 12 months. The explanted valves were examined histologically and
      biochemically. RESULTS: After explantation XB showed severe cusp degeneration,
      which resulted in severe valvular regurgitation. In comparison, XA appeared
      macroscopically normal with preserved valvular function. The surface of XB were
      covered with an incomplete endothelial multilayer. The extracellular matrix (ECM)
      of XB showed pathological amounts of collagenous and elastic fibers as well as
      proteoglycan content combined with an increase cellularity. The XA were
      completely repopulated by an endothelial cell monolayer; the ECM was repopulated
      with a myofibroblast population comparable to native ovine heart valve tissue.
      CONCLUSIONS: Approaches to heart valve engineering based on
      acellularized/xenogenic matrices provide promising results and will hopefully led
      to the "ideal" valve substitute in clinical heart valve replacement.

PMID- 14634764
TI  - Concomitant CABG-procedures in elderly patients undergoing aortic valve
      replacement. An additional risk factor?
AB  - OBJECTIVE: Preoperative coronary angiography in elderly people referred to the
      hospital for aortic valve replacement (AVR) often shows additional significant
      stenoses of the coronary arteries (CAD). The benefit of concomitant coronary
      artery bypass grafting (CABG) in these patients is still discussed
      controversially. By some authors, an isolated AVR in elderly patients with
      additional CAD is even described to have a better outcome. PATIENTS AND METHODS:
      We analyzed 283 patients (> or =75 years), undergoing AVR with or without
      concomitant CABG-procedures. We particularly analyzed those patients who were
      operated with an isolated AVR in spite of preoperatively known CAD. There were
      166 patients in the AVR group (gr. A) and 117 patients in the AVR+CABG group (gr.
      AC). 51 of these patients with isolated AVR were preoperatively known to have an
      additional CAD (stenoses <60%) (gr. A2), whereas 115 patients of group A only
      suffered from an isolated aortic valve disease (gr. A1). RESULTS: Comparing group
      A and AC, we found a significantly prolonged mechanical ventilation in group AC
      (22.3+/-5.3 hours vs 10.1+/-1.9 h in gr. A, p<0.05) and a longer stay on the ICU.
      The incidence of severe postoperative complications and the in-hospital mortality
      were comparable. In group A2 we could differ between stenoses of the LAD (n=19)
      and of the right coronary or circumflex artery (n=32). The decision not to bypass
      a stenosis of the LAD caused a significantly worse outcome of these patients
      compared to group AC. Ignoring stenoses of the RCA or RCx was not correlated with
      an impaired postoperative result. CONCLUSIONS: With our results we could not
      identify concomitant CABG as a predictor of poor surgical outcome in elderly
      patients with AVR. We could even show that an additional bypass grafting of
      moderate stenoses of the LAD is important for a good outcome of these patients.
      Comparable stenoses in the right coronary or circumflex artery may be ignored
      with the advantage of a shorter period of intraoperative ischemia and the
      possibility of a secondary catheter intervention.

PMID- 14634765
TI  - [Left ventricular pseudoaneurysm after mitral valve replacement].
AB  - We report about a woman with a rare complication after mitral valve replacement
      24 years ago. The patient had a massive hemorrhage some hours after operation. We
      performed invasive diagnostics because of an increasing pressure gradient across
      the prosthesis and revealed a left ventricular pseudoaneurysm. Before the planned
      reoperation the patient died suddenly. As the cause of death, we assumed a
      rupture of the pseudoaneurysm.

PMID- 14634766
TI  - [Radiation-induced cardiac disease].
AB  - Radiation-induced effects may damage various cardiac structures chronically and
      cause heart valve dysfunction as well as occlusive lesions of coronary and other
      arteries exposed to radiation. A 72-year-old woman with a history of radiation
      treatment after breast cancer was admitted 25 years later with symptoms of
      tachycardia and acute dyspnea. We found valvular thickening, medium to severe
      valvular dysfunction and high grade occlusive coronary artery disease in proximal
      portions. The left subclavian artery also was affected. Surgical treatment was
      required immediately. Long-term follow-up cardiac evaluation even in asymptomatic
      patients is mandatory to uncover cardiac injuries by radiation. To lower the risk
      and maximize the benefit, early intervention by valvular replacement and
      myocardial revascularization is indicated. Restrictive myopathy and chronic
      pericarditis increase risk and have to be clarified. Diagnosis in these radiation
      exposed patients can be made by typical findings. Echocardiography is of eminent
      relevancy.

PMID- 14634767
TI  - [Myocardial infarction after influenza vaccination].
AB  - Influenza is a common disease in the population. Influenza vaccination is
      performed routinely and is usually well tolerated. Minor local or systemic side
      effects like fever and myalgia are described. Rarely there are more severe
      adverse events. Systemic vasculitis has been reported in some cases. In this case
      we report on a female patient with secondary vasculitis and myocardial infarction
      after influenza vaccination. The patient received cortisol and recovered. The
      literature about influenza vaccination, its side effects and recommendations
      about vaccination in patients with coronary artery disease is reviewed.

PMID- 14634768
TI  - Is left ventricular hypertrabeculation/ noncompaction a cardiac manifestation of
      Fabry's disease?
AB  - BACKGROUND AND OBJECTIVES: Some types of hypertrophic cardiomyopathy are due to
      cardiac Fabry's disease. Since left ventricular hypertrabeculation/noncompaction
      (LVHT) is regarded a subtype of hypertrophic cardiomyopathy, we looked for the
      alpha-galactosidase levels in blood leukocytes of LVHT patients. METHODS:
      Included were male patients in whom LVHT was diagnosed between June 1995 and
      September 2002. Echocardiographic criteria for LVHT were 1) >3 trabeculations
      protruding from the left ventricular wall, apically to the papillary muscles,
      visible in 1 image plane, and 2) intertrabecular spaces perfused from the
      ventricular cavity, as visualised on colour Doppler imaging. Trabeculations were
      defined as structures with the same echogenicity as the myocardium and moving
      synchronously with the ventricular contractions. Excluded were patients with
      known neuromuscular disorders. All patients were asked for systemic
      manifestations of Fabry's disease and blood tests were taken. The alpha
      galactosidase-A activity was determined by means of an established fluorometric
      assay in blood leukocytes. RESULTS: Forty-one patients were invited and 26
      accepted the invitation. The remaining patients had died (n=5), lived abroad
      (n=5) or were unwilling (n=5). Among the 26 patients, aged 28-78 years, who
      followed the invitation, one had renal failure due to renal shrinkage and one had
      suffered from a stroke 3 years previously. Leukocyte alpha-galactosidase levels
      ranged from 70 to 188 nM/mg Prot/h (normal: > or =42 nM/mg Prot/h). In none of
      the patients was the alpha-galactosidase level reduced. CONCLUSION: LVHT does not
      seem to be a manifestation of cardiac Fabry's disease. To definitively exclude
      Fabry's disease, however, endomyocardial biopsy is required.

PMID- 14634773
TI  - Evaluation of lateral lymph node dissection with preoperative chemo-radiotherapy
      for the treatment of advanced middle to lower rectal cancers.
AB  - BACKGROUND AND AIMS: This study examined rectal cancers with lateral lymph node
      (LN) metastases and whether lateral lymph node dissection (LLD) with or without
      preoperative chemo-radiotherapy (XRT) benefits patients with rectal cancer.
      PATIENTS AND METHODS: A total of 452 consecutive cases of curatively resected
      pT2, pT3, and pT4 middle to lower rectal cancers were retrospectively analyzed.
      Of these, 265 patients underwent curative LLD and 155 XRT. Data were evaluated
      with respect to the cumulative percentage of survival. RESULTS: Lateral LN
      metastases were identified in 7.7% of patients. Of the pT3/pT4 extraperitoneal
      cancer patients 13.5/18.8% had lateral LN metastases. In the treatment of middle
      rectal cancers and pT2 extraperitoneal cancers LLD either with or without XRT did
      not improve survival rate. For the treatment of pT3/pT4 extraperitoneal tumors
      prior to the introduction of total mesorectal excision (TME) in 1994 LLD plus XRT
      yielded significantly better survival and local control than conventional surgery
      without LLD or XRT, although LLD alone did not improve either survival or local
      recurrence rates. Since 1995 TME with or without subsequent LLD has yielded
      favorable results for the treatment of extraperitoneal tumors. CONCLUSION: For
      the treatment of middle rectal cancers and pT2 extraperitoneal cancers LLD either
      with or without XRT does not improve survival rate. For pT3/pT4 extraperitoneal
      tumors, which are associated with a high incidence of lateral node metastasis,
      combining treatment modalities such as TME followed by LLD or XRT followed by TME
      may be considered.

PMID- 14634774
TI  - Lateral lymph node dissection in rectal cancer patients: is there any indication?

PMID- 14634775
TI  - Humoral immune response to p53 correlates with clinical course in colorectal
      cancer patients during adjuvant chemotherapy.
AB  - BACKGROUND AND AIMS: Overexpression of p53 protein in malignancies induces an
      immune response in some cancer patients. We investigated whether production of
      serum antibodies against p53 (p53-Ab) is associated with pathohistological
      parameters of colorectal carcinoma and whether p53-Ab can serve as a tumor marker
      during cancer treatment. PATIENTS AND METHODS: Serum samples from 220 colorectal
      cancer patients during surgery and adjuvant chemotherapy and 42 healthy controls
      were tested for the presence of p53-Ab by ELISA. Expression of p53 protein in
      tumors was determined using mouse anti-human p53-Ab. RESULTS: Serum p53-Ab were
      detected in 18% of patients while all controls were negative. A strong
      correlation between p53-Ab production and p53 protein expression was observed:
      70% of p53-Ab positive cases had tumors positive for p53 vs. 52% of p53-Ab
      negative cases. There was also a significant predominance of p53-Ab positive
      cases in Dukes' stages B and C over stage A. Although surgery alone reduced p53
      Ab levels, decreases in p53-Ab titer became significant midterm through
      chemotherapy compared to both pre- and postoperative values and remained
      decreased until the completion of treatment. CONCLUSION: The presence of p53-Ab
      in sera of patients with colorectal cancer indicates tumors in more advanced
      histopathologic stages (Dukes' B, C). Due to low sensitivity (18%) p53-Ab are not
      recommendable as a preoperative marker for colorectal cancer. However, due to
      high specificity (100%), their monitoring after surgery and adjuvant chemotherapy
      has potential for early diagnosis of tumor relapse in p53-Ab positive cases.

PMID- 14634776
TI  - Prognostic value of disseminated colorectal tumor cells in the liver: results of
      follow-up examinations.
AB  - BACKGROUND AND AIMS: Dissemination of tumor cells is an initial step in
      metastatic disease. Detection of disseminated tumor cells (DTC) in blood, bone
      marrow and lymph nodes has been associated with reduced disease-free survival,
      but to date there are no data for hepatic DTC. We investigated the prognostic
      relevance of hepatic DTC that are present in patients with colorectal cancer
      (CRC) at the time of surgery. PATIENTS AND METHODS: In 121 patients with CRC
      clinically diagnosed for liver metastasis by ultrasound, CT, and exploration
      during surgery DNA from liver biopsy specimens obtained during surgery was
      examined by a PCR-RFLP assay for K-ras mutations as a marker for DTC. At the time
      of surgery 54 of the 121 were mutated in K-ras codons 12 or 13. After a median
      follow-up of 405 days all survivors were reevaluated by ultrasound/CT. RESULTS:
      Patients with a K-ras mutation in their primary tumor had a significantly lower
      probability of survival and higher risk of harboring a synchronous second
      colorectal carcinoma than patients with a K-ras wild-type tumor. Based on
      specimens taken intraoperatively DTC were found in the liver of 14 of 54 patients
      (26%). At follow-up only 10 of 40 patients (25%) with DTC-free liver had died of
      their disease but 9 of the 14 patients with hepatic DTC. Among the 14 patients
      with hepatic DTC 10 (71%) had developed new liver metastasis, compared to 12 of
      40 (30%) in those without hepatic DTC. CONCLUSION: Hepatic DTC in colorectal
      cancer patients is associated with reduced overall survival and increased risk of
      hepatic metastasis development. Further studies are necessary to corroborate our
      results since the number of patients studied is still limited.

PMID- 14634777
TI  - Growing burr hole: enlarging pseudomeningocele at the site of a craniostomy.
AB  - BACKGROUND: Growing skull fractures and other enlarging skull defects are rare
      postoperative occurrences. We report here on a 10-month-old girl who presented
      with an enlarging burr hole and pseudomeningocele after an endoscopic third
      ventriculocisternostomy. METHODS: Evaluation of an enlarging subcutaneous mass at
      the site of the burr hole included computed tomography scans and magnetic
      resonance imaging, which revealed a pseudomeningocele. The patient underwent
      repair of the lesion, including dural closure and cranioplasty. CONCLUSIONS:
      Growing skull fractures or other enlarging bone defects may occur after burr hole
      placement, particularly in infants who require larger access sites for endoscopy.

PMID- 14634778
TI  - Spinal extradural angiolipoma, with a literature review.

PMID- 14634779
TI  - Changes in taste receptor cell sensitivity in a polyphagous caterpillar reflect
      carbohydrate but not protein imbalance.
AB  - Caterpillars of the polyphagous arctiid, Grammia geneura, have a single cell in
      the medial galeal sensillum that responds to some sugars and to some amino acids.
      After conditioning on artificial diet containing unbalanced amounts of
      carbohydrate and protein, the responses of this cell alter. After protein-biased
      food it increases slightly, but after carbohydrate-biased food it decreases.
      Responses to both sucrose and amino acids change in the same direction and the
      changes would not provide the information necessary to redress a shortage of
      protein. The lateral galeal sensillum contains one cell that responds to fructose
      and another responding to some amino acids. The responses of each of these cells
      in the lateral sensillum are not consistently affected by conditioning diets.
      After conditioning for 20 h on a protein- or carbohydrate-biased diet, the
      insects started to feed without delay if offered carbohydrate-biased diet, but
      only after a pause if given protein-biased diet. This occurred irrespective of
      the conditioning diet. The duration of the first feeding bout was also longer on
      carbohydrate-biased diet and the longest bouts followed protein-biased
      conditioning.

PMID- 14634780
TI  - Dose and image quality in the comparison of analogue and digital techniques in
      paediatric urology examinations.
AB  - In paediatric radiology it has been recognised that children have a higher risk
      of developing cancer from the irradiation than adults (two to three times);
      therefore, increased attention has been directed towards the dose to the patient.
      In this study the effect on patient dose and image quality in replacing the
      exposure in micturating cystourethrography (MCUG) examinations with the stored
      fluoroscopy image has been investigated. In the intravenous urography (IVU)
      examination we compared analogue and digital image quality, but the dose
      measurements were performed on a phantom. Standard clinical X-ray equipment was
      used. Sixty-eight patients in each of two centres were studied for the MCUG.
      Doses were measured with a dose-area product (DAP) meter and the image quality
      was scored. A non-parametric statistical analysis was performed. For the IVU, a
      phantom was used in the dose measurements but clinical images were scored in the
      comparison between analogue and digital images. For the MCUG, replacing the
      exposure with stored fluoroscopy images lowered the DAP value from 0.77 to 0.50
      Gy cm2. The image quality did not show any difference between the techniques;
      however, if reflux was to be graded, exposure was needed. For the IVU, the doses
      could be lowered by a factor of 3 using digital techniques. The image quality
      showed no statistical difference between the two techniques. There is a potential
      for a substantial dose reduction in both MUCG and IVU examinations using digital
      techniques.

PMID- 14634782
TI  - Oral contrast agents for small bowel MRI: comparison of different additives to
      optimize bowel distension.
AB  - The purpose of this study was to compare two osmotic carbohydrate sugar alcohols
      (mannitol 2.5% and sorbitol 2.5%, 2.0%, and 1.5% watery solutions) in combination
      with 0.2% locust bean gum (LBG) for small bowel distension for MR imaging. Small
      bowel distension was quantified on coronal 2D TrueFISP images by measuring the
      diameters of 16 small bowel loops in each of 12 healthy subjects (age range 31-55
      years). Additionally, the grade of small bowel distension was rated
      qualitatively. Patient acceptance concerning nausea, vomiting, flatulence, and
      diarrhea was noted for each solution, and all results were compared by a Wilcoxon
      test or t test, respectively. The ingestion of water combined with LBG and either
      2.5% mannitol or 2.0% sorbitol showed the best distension of the small bowel. The
      lowest side effect rate was observed following ingestion of sorbitol in a
      concentration of 2.0 and 1.5%. Based on these data, we recommend a combination of
      LBG and 2% sorbitol use for optimal bowel distension and minimal side effects
      resulting in enhanced patient acceptance.

PMID- 14634783
TI  - CT findings and serum ca 125 levels in malignant peritoneal mesothelioma: report
      of 11 new cases and review of the literature.
AB  - The aim of this study was to review and reappraise the clinical and CT features
      of malignant peritoneal mesothelioma (MPM), and to discuss differential
      diagnosis. The history, clinical, and laboratory data, and imaging studies of 11
      patients with a histologically proven diagnosis of MPM, were retrospectively
      reviewed. Our patients consisted of 7 women and 4 men, with a median age of 48
      years (age range 40-55 years). There was a definite history of significant
      asbestos exposure in 6 patients. Abdominal swelling (9 of 11) was the most common
      presenting symptom. The mean serum CA-125 (normal value 1.2-32 U/ml) level was
      230 U/ml (range 19-1000 U/ml). The most common radiological findings were
      extensive or moderate amounts ascites (11 of 11), irregular or nodular peritoneal
      thickening (11 of 11), omental involvement (10 of 11), mesentery involvement (9
      of 11), pleural thickening, plaques or calcification (7 of 11), pleural effusion
      (6 of 11), and bowel wall thickening (5 of 11). Two patients had large upper
      abdominal masses. Computed tomography findings of MPM are nonspecific and
      inadequate to pinpoint specific diagnosis. The diagnosis requires histological
      demonstration which is commonly made by an image or laparoscopic-guided biopsy.
      Pleural changes suggesting asbestosis combined with CT findings and high CA-125
      levels can suggest, but are not diagnostic of, mesothelioma. Suggesting the
      diagnosis of MPM is important because histological and immunohistochemical tests
      are needed for diagnostic accuracy.

PMID- 14634784
TI  - Quantitative MR evaluation of body composition in patients with Duchenne muscular
      dystrophy.

PMID- 14634786
TI  - Chimeric RNA/DNA oligonucleotide-directed gene targeting in rice.
AB  - Site-specific mutagenesis in a rice genome was obtained by introducing chimeric
      RNA/DNA oligonucleotides (COs) by means of particle bombardment. Three COs were
      designed to target the independent codons for Pro-171, Trp-548 and Ser-627 of the
      endogenous rice acetolactate synthase (ALS) gene so it would confer resistance to
      ALS-inhibiting herbicides. Sequencing of the ALS gene of herbicide-resistant
      plants demonstrated that the ALS sequence was modified in a site-specific
      fashion. The efficiency of gene conversion mediated by COs was estimated to be
      1x10(-4). These results demonstrate that CO-directed gene targeting is feasible
      in rice.

PMID- 14634787
TI  - Use of complementary and alternative medicine by arthritis patients in a
      university hospital clinic serving rheumatology patients in Korea.
AB  - There is a paucity of data regarding the use of and attitudes toward
      complementary and alternative medicine (CAM) among arthritis patients in Asia.
      This study was performed to assess the use of CAM, related demographic and
      clinical factors, and attitudes among Korean arthritis patients. We conducted a
      survey of patients in rheumatology clinics affiliated with a university hospital.
      One hundred fifty patients (68.5%) reported using at least one form of CAM during
      the previous 12 months. Herbal remedies and acupuncture were the most frequently
      used categories of CAM. Among the parameters analyzed, income level was
      significantly and negatively associated with frequent or regular use of CAM.
      Dialogue about CAM use with Korean patients does not seem to have been initiated
      yet, as the main reason given for not discussing CAM use with physicians was "not
      being asked."

PMID- 14634788
TI  - Myocardial infarction caused by rheumatoid vasculitis: histological evidence of
      the involvement of T lymphocytes.
AB  - Rheumatoid arthritis (RA) is a chronic joint disease that can be complicated with
      extra-articular manifestations due to vasculitis. We describe a patient with RA
      who developed systemic vasculitis and died of myocardial infarction. Autopsy
      demonstrated vasculitis of the left anterior descendent and circumflex coronary
      arteries, which were narrowed or occluded with organizing thrombosis. Formation
      of granuloma with multinucleated giant cells was also observed in media of the
      circumflex artery. There was no microscopic evidence of atheroma formation in the
      coronary arteries. Of note, there was a follicle-like infiltration of CD45RO
      positive T lymphocytes in interna of the left coronary arteries and the right
      renal artery. Although not frequently reported, coronary vasculitis as a cause of
      myocardial infarction should be considered in patients with RA. Moreover, our
      results suggest that infiltration of T lymphocytes might be involved in the
      development of rheumatoid vasculitis.

PMID- 14634789
TI  - Agrobacterium-mediated insertional mutagenesis (AIM) of the entomopathogenic
      fungus Beauveria bassiana.
AB  - Agrobacterium tumefaciens was used to stably transform the entomopathogenic
      deuteromycete Beauveria bassiana to hygromycin B resistance by integration of the
      hph gene of Escherichia coli into the fungal genome. The transformation protocol
      was optimized to generate a library of insertion mutants of Beauveria.
      Transformation frequencies around 10(-4) and suppression of background growth
      were achieved. Over 90% of the AIM mutants investigated contained single-copy T
      DNA integrations at different chromosomal locations. Integrated T-DNAs were re
      isolated from ten transformants by a marker rescue approach. When the sequences
      flanking these T-DNAs were compared with the corresponding locations of the wild
      type genome, truncations of T-DNA borders were found to be common, while none of
      the sites of integration had suffered deletion or rearrangement. Thus, AIM can be
      considered a promising tool for insertional mutagenesis studies of
      entomopathogenic filamentous fungi.

PMID- 14634790
TI  - The cardiovascular safety of high-dose intravenous granisetron in cancer patients
      receiving highly emetogenic chemotherapy.
AB  - OBJECTIVES: To assess the cardiovascular safety, tolerability and efficacy of
      high doses of granisetron for the treatment of nausea and vomiting in patients
      undergoing highly emetogenic chemotherapy. METHODS: Patients with histologically
      confirmed malignant disease were given an intravenous infusion of granisetron,
      160 microg/kg, over 30 min, starting 15 min after highly emetogenic chemotherapy.
      Patients underwent cardiac monitoring for 24 h following the granisetron
      infusion. Pulse, blood pressure and electrocardiogram (lead II and ambulatory)
      measurements were taken, and routine clinical chemistry and haematology tests
      performed. Blood samples for pharmacokinetic analysis were taken before the
      granisetron infusion, and at intervals afterwards. Adverse events were self
      assessed using a symptom checklist. Self-assessment categorical rating scales
      were used to evaluate patient nausea, vomiting and retching. RESULTS: Ten
      patients (eight females and two males; average age 41.5 years) completed the
      trial and were included in the safety and efficacy assessments. No clinically
      relevant changes in electrocardiogram, pulse rate, blood pressure or laboratory
      parameters were observed. Furthermore, in the 7 days following dosing there were
      no serious adverse events leading to withdrawal from the trial. A complete
      response (no vomiting, retching or, at most, mild nausea) was experienced by five
      patients. Six patients had no, or mild, nausea and an additional two patients
      vomited on a maximum of two occasions. Additional antiemetic rescue medication
      was given to three patients during the 24-h trial period. Despite considerable
      interpatient variability, C(max) and AUC parameters were proportionally greater
      than values reported for lower doses of granisetron. CONCLUSIONS: Granisetron
      administered at four times the upper recommended dose demonstrated good efficacy
      and tolerability with no clinically important cardiac effects.

PMID- 14634791
TI  - Population pharmacokinetics of short intravenous vinorelbine infusions in
      patients with metastatic breast cancer.
AB  - PURPOSE: To develop a population pharmacokinetic model of vinorelbine
      administered by short intravenous infusion in metastatic breast cancer patients.
      METHODS: Vinorelbine was administered as infusions of 5-10 min at 15, 20 or 25
      mg/m(2) to 30 patients. Blood samples were collected over 18 h. Plasma
      concentrations of vinorelbine were determined by HPLC. Population pharmacokinetic
      analysis was performed using a nonlinear mixed effects modeling method. RESULTS:
      Vinorelbine concentration-time profiles were best described by a three
      compartment open model. Plasma clearance (CL) was high and positively related to
      lean body weight (LBW) and body surface area (BSA) or to a combination of height
      and body weight (BW). Elevated serum alkaline phosphatases had a negative effect
      on CL. Typical population estimates of CL and central distribution volume (V(1))
      were 74.2 l/h and 7.8 l, respectively. The interindividual population
      coefficients of variation for CL and V(1) were 17.0% and 32.0%, respectively. The
      stability and predictive performance of the final population pharmacokinetic
      model were assessed using 200 bootstrap samples of the original data. CONCLUSION:
      This study identified combined effects of BSA and serum alkaline phosphatases on
      clearance. These results partly support the conventional dose adjustment of
      vinorelbine based on BSA, but suggest dose modification in cases of extreme
      values of serum alkaline phosphatases.

PMID- 14634792
TI  - L-Asparagine depletion levels and L-asparaginase activity in plasma of children
      with acute lymphoblastic leukemia under asparaginase treatment.
AB  - PURPOSE: To determine the minimum levels of L-asparaginase (ASNase) activity
      necessary to maintain L-asparagine (Asn) depletion under ASNase treatment in
      acute lymphoblastic leukemia (ALL). METHODS: We measured ASNase activity using an
      enzyme coupling method with a limit of detection of 2 U/l and examined the
      relationship between ASNase activity and Asn levels in blood samples from 14
      children with ALL. RESULTS: In all but one patient showing high ASNase antibody
      titers, minimum ASNase activity to maintain Asn depletion levels below the limit
      of detection (40 ng/ml) ranged from 6 to 180 U/l with a median value of 16 U/l.
      In 11 patients, the enzyme activity corresponding to minimum detectable Asn
      levels ranged from 2 to 32 U/l with a median value of 6.5 U/l. Patients with an
      ASNase activity of 2 U/l or an undetectable activity (<2 U/l) had nearly normal
      Asn levels: 4140+/-1161 ng/ml at 2 U/l and 7235+/-3107 ng/ml at <2 U/l (mean+/
      SD). Statistical analysis showed that ASNase activity in the range of 2-32 U/l
      was inversely correlated with Asn levels ( r=-0.803, P=0.001). CONCLUSION: These
      results show that Asn levels are strongly correlated with plasma ASNase activity
      even at low enzyme activities (<50 U/l) and that this sensitive ASNase assay can
      be used to estimate plasma Asn depletion levels.

PMID- 14634793
TI  - Decreased frequency of HLA-B35 in patients with gastric MALT lymphoma.
AB  - Persistent infection with Helicobacter pylori has been shown to be strongly
      associated with the development of low-grade gastric mucosa-associated lymphoid
      tissue (MALT) lymphoma. However, the prevalence of H. pylori infection exceeds
      the incidence of MALT lymphoma by far. This discrepancy might at least partially
      be explained on a genomic basis of the host. To evaluate the association between
      HLA type and MALT lymphoma, we investigated 46 patients with MALT lymphoma
      recruited in a prospective multicenter study from October 1998 to March 2001.
      Over 13,000 voluntary stem cell donors from over 40 German blood banks
      represented the control group. Exploratory statistical analysis using Fisher's
      exact test showed significantly decreased frequency of HLA-B35 in the MALT
      lymphoma group compared to the control group. Our data suggest a negative
      association between HLA-B35 and MALT lymphoma; however, larger studies are
      necessary to confirm a protective role of this HLA antigen.

PMID- 14634794
TI  - Strengthening editors' policy concerning publication of anatomic variations.

PMID- 14634795
TI  - Trials and tribulations of immunotherapy as a treatment option for patients with
      squamous cell carcinoma of the head and neck.
AB  - Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial
      malignancy that is the sixth most common neoplasm in the world. Despite numerous
      advances in treatments involving surgery, radiation, and chemotherapy, the 5-year
      survival has remained at less than 50% for the last 30 years primarily due to
      local recurrences [66]. Consequently, the possibility of developing
      immunotherapeutic approaches as a treatment for HNSCC has gained interest. The
      present review has 3 objectives pertaining to immunotherapeutic means to treat
      HNSCC patients: (1) to summarize the feasibility of such approaches, (2) to
      provide an overview of the obstacles to attaining protective immune reactivity,
      and (3) to consider how these obstacles can be overcome to stimulate immune
      reactivity to HNSCC. These objectives will also be considered in the context of
      what lessons have been learned from immunotherapeutic trials for other solid
      malignancies and the applicability of this information to HNSCC.

PMID- 14634796
TI  - Identification of new prostate stem cell antigen-derived peptides immunogenic in
      HLA-A2(+) patients with hormone-refractory prostate cancer.
AB  - PURPOSE: Prostate cancer refractory to hormonal manipulation requires new
      treatment modalities. In the present study we attempted to identify prostate stem
      cell antigen (PSCA)-derived peptides immunogenic in HLA-A2+ prostate cancer
      patients in order to develop peptide-based immunotherapy against hormone
      refractory prostate cancer (HRPC). METHODS: Eleven different PSCA-derived
      peptides, which were prepared based on the HLA-A2 binding motif, were examined to
      determine whether they would be recognized by cellular and humoral immune
      responses in 12 HLA-A2+ patients (11 with HRPC and 1 with non-HRPC). RESULTS:
      Among the PSCA-derived peptides, PSCA 7-15 and PSCA 21-30 peptides effectively
      induced HLA-A2-restricted peptide-specific and tumor-reactive cytotoxic T
      lymphocytes (CTLs) from peripheral blood mononuclear cells (PBMCs) of HLA-A2+
      patients. The PSCA 21-30 peptide was capable of inducing peptide-specific CTLs in
      both cancer patients and healthy donors, whereas the PSCA 7-15 peptide was
      immunogenic in only cancer patients. Immunoglobulin G (IgG) reactive to the PSCA
      21-30 peptide was detected in plasma of most patients and healthy donors, whereas
      IgG reactive to PSCA 7-15 was undetectable in all cases. These results indicate
      that the former peptide elicits both cellular and humoral immune responses in
      both patients and healthy donors, whereas the latter elicits only cellular
      responses in patients. CONCLUSION: These two PSCA peptides should be considered
      for use in clinical trials of immunotherapy for HLA-A2+ HRPC patients.

PMID- 14634797
TI  - Temperature optima of enzyme-catalysed reactions in microemulsion systems.
AB  - Ternary phase systems (water/surfactant/organic solvent) were utilised to
      increase and broaden the temperature optima of enzyme-catalysed reactions.
      Alcohol dehydrogenases from yeast and Thermoanaerobium brockii (EC 1.1.1.1 and EC
      1.1.1.2), lactate dehydrogenase from Lactobacillus delbrueckii (EC 1.1.1.28) and
      the particulate hydrogenase from Ralstonia eutropha (EC 1.18.99.1) were used as
      model enzymes in microemulsions, consisting of the surfactant Aerosol OT, and
      various alkane solvent and aqueous phases. All enzymes exhibited, besides an
      increase in specific activity, an upshift of the temperature optimum of the
      catalysed reaction. The temperature optimum could be further shifted by variation
      of the chain length of the solvent used and/or the addition of compatible solutes
      to the aqueous phase. Under optimised conditions, catalytic reactions of enzymes
      from mesophilic microorganisms had temperature optima in the range generally
      obtained with enzymes from thermophilic organisms.

PMID- 14634798
TI  - Enzymatic assay for perfluoro-tagged metabolites of l-DOPA using crude lysate
      from E. coli transformed with pKKAADCII.
AB  - Isomers of l-DOPA and dopamine with a nine-atom 19F atom tag were exposed to
      aromatic acid decarboxylase (AADC) in the lysate of Escherichia coli JM109 that
      had been transformed with the plasmid pKKAADCII. The resulting samples were
      analyzed with HPLC. The first study investigated the conversion of the tagged l
      DOPA into tagged dopamine, using the tagged dopamine as a standard. A second
      study was undertaken to identify the source of peaks seen in the enzymatic
      assays. l-DOPA with the tag bonded at position 5 served as the best substrate for
      AADC. Isomers that fit into the active site of AADC are likely to follow the
      biosynthetic path for dopamine in vivo and are potentially useful in magnetic
      resonance studies. The enzymatic assay described here provides an efficient and
      cost-effective tool for screening new compounds for use in the fluorine imaging
      of neural pathways.

PMID- 14634799
TI  - Expression of exogenous genes in Trypanosoma cruzi: improving vectors and
      electroporation protocols.
AB  - To improve transfection efficiency in Trypanosoma cruzi, we developed a new
      electroporation protocol and expression vectors which use luciferase and green
      and red fluorescent proteins as reporter genes. In transient transfections, the
      electroporation conditions reported here resulted in luciferase expression 100
      times higher than the levels obtained with previously described protocols. To
      verify whether sequences containing different trans-splicing signals influence
      reporter gene expression, we compared DNA fragments corresponding to 5'
      untranslated plus intergenic (5' UTR plus Ig) regions from GAPDH, TcP2beta, alpha
      and beta- tubulin and amastin genes. Vectors containing sequences derived from
      the first four genes presented similar efficiencies and resulted in luciferase
      expression in transiently transfected epimastigotes that was up to 10 times
      higher than that for a control vector. In contrast, the amastin 5' UTR plus Ig
      resulted in lower levels of reporter gene expression. We also constructed a
      vector containing an expression cassette designed to be targeted to the tubulin
      locus of the parasite.

PMID- 14634800
TI  - Influence of verapamil on the pharmacokinetics of the antiparasitic drugs
      ivermectin and moxidectin in sheep.
AB  - P-Glycoprotein (P-GP) is a transport protein that participates in the mechanism
      of active secretion of different molecules from the bloodstream to the
      gastrointestinal tract. The aim of the current work was to evaluate the effect of
      verapamil, a P-GP substrate, on the pharmacokinetic behaviour of the
      anthelmintics ivermectin and moxidectin in sheep. Thirty-two sheep were divided
      into four groups and treated orally with either ivermectin or moxidectin alone
      (200 micro g/kg) or co-administered with verapamil at 3 mg/kg (three times at 12
      h intervals). Blood samples were collected over 30 days post-treatment and plasma
      was analysed to determine ivermectin and moxidectin concentrations by HPLC. The
      ivermectin peak concentration was significantly higher ( P=0.048) after
      ivermectin plus verapamil, compared with the ivermectin alone treatment.
      Ivermectin plasma availability was significantly higher following co
      administration ( P=0.022). Verapamil had no effect on the kinetics of moxidectin.
      The significant alteration in the plasma disposition of ivermectin in sheep
      induced by verapamil, possibly due to interference with a P-GP-mediated
      elimination mechanism, may have an important impact on efficacy against resistant
      or rate-limiting-parasites and on the persistency of its antiparasitic activity.

PMID- 14634801
TI  - Immunohistochemical determination of HER-2/neu, c-Kit (CD117), and vascular
      endothelial growth factor (VEGF) overexpression in malignant melanoma.
AB  - PURPOSE: To determine the prevalence and evaluate the possible prognostic value
      of the molecular targets in malignant melanoma, we studied the overexpression of
      HER-2/neu, c-Kit, and vascular endothelial growth factor (VEGF) in this patient
      population. MATERIALS AND METHODS: Overexpression of HER-2/neu, c-Kit, and VEGF
      was evaluated using immunohistochemical assays in 202 archival tissue specimens.
      RESULTS: Only two patients (0.9%) revealed HER-2/neu overexpression, whereas 46
      (22.8%) revealed c-Kit and 42 (20.8%) specimens showed VEGF overexpression.
      Multivariate analysis performed did not show a significant difference in survival
      between c-Kit-positive and c-Kit-negative groups (P = 0.36) and VEGF-positive and
      VEGF-negative groups (P = 0.25). Interestingly, c-Kit was more likely to be
      overexpressed in the superficial spreading type and VEGF was overexpressed
      preferentially in the amelanotic melanoma type. CONCLUSIONS: HER-2/neu has no
      role in melanogenesis. Both c-Kit (expressed in superficial spreading disease)
      and VEGF (expressed in amelanotic melanoma) may have significant therapeutic
      implications as molecular targets, which warrants further investigation.

PMID- 14634802
TI  - Induction of differentiation and peroxisome proliferator-activated receptor gamma
      expression in colon cancer cell lines by troglitazone.
AB  - PURPOSE: We investigated the relationship between the effects of troglitazone
      (TGZ) on cellular growth, differentiation and apoptosis induction, and the
      induction of peroxisome proliferator-activated receptor (PPAR) gamma in three
      human colon cancer cell lines, HCT-15, DLD-1and LoVo. METHODS: Viable cell number
      was evaluated by the Alamar blue assay and apoptotic cell death by TUNEL methods.
      Expression of PPARgamma mRNA and protein was examined by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot, respectively. The
      differentiation markers of colonic mucosa, villin and MUC2 mRNAs, were analyzed
      by real-time RT-PCR. RESULTS: HCT-15 and DLD-1 cells proliferated rapidly while
      LoVo cells grew slowly. TGZ dose-dependently inhibited the proliferation of all
      the cell lines, and also induced apoptotic cell death. High expression of
      PPARgamma mRNA and protein was demonstrated in DLD-1 and LoVo cells before TGZ
      treatment. After the treatment, PPARgamma mRNA and protein levels were increased
      in HCT-15 and LoVo cells. Villin and MUC2 mRNAs were increased by TGZ treatment
      in HCT-15 cells while villin mRNA was repressed in LoVo cells. Changes in
      expression of PPARgamma, villin or MUC2 mRNAs were not observed in DLD-1 cells.
      CONCLUSIONS: These results suggest that PPARgamma levels are not correlated with
      the rates of cell proliferation. Differentiation induction by TGZ was only
      observed in the cell lines with enhanced PPARgamma expression.

PMID- 14634803
TI  - Long-term outcome of patients with urea cycle disorders and the question of
      neonatal screening.
AB  - With regard to the principles established for neonatal population screening, the
      question arises whether for patients with urea cycle disorders there is an
      accepted treatment which really affects the disease course and prognosis as
      compared to the natural history of these diseases. A retrospective study of 88
      patients was performed. Based on questionnaires, the survival rate and
      neurodevelopmental outcome of patients treated with protein restriction alone was
      compared to the new therapy introduced in the 1980s with added
      citrulline/arginine, essential amino acids for improving the amino acid
      composition of the restricted natural protein and benzoate. Survival of patients
      with neonatal presentation was improved by the extensive therapy but this mostly
      at the cost of an increasing number of retarded patients. Long-term outcome did
      not differ significantly between the two treatments. Of all patients, 56% were
      symptomatic within 4 days of age and 67% within the 1st week. Thus a prevention
      of irreversible damage by neonatal screening on blood obtained at 3-4 days of
      life is questionable. Whether the benefit of obtaining a rapid diagnosis, e.g.
      for allowing proper counselling and prospective treatment, is acceptable for the
      parents of prospective patients remains open. The organisation of a dense network
      of specialised metabolic centres with sufficient staff and resources is a prior
      condition for any screening programme in order to ensure the rapid diagnosis,
      follow-up of treatment and counselling of a cumulative number of affected chronic
      patients needing this support. A commitment on a long-term basis by the
      institutions is needed in view of the health budget restrictions. CONCLUSION: in
      the short term, the goal is to detect hyperammonaemic patients as early as
      possible with special emphasis on sick neonates. In practice, quantitative plasma
      ammonia determination without delay is recommended in any newborn for whom a
      sepsis work-up is considered and in children who refuse feeding or vomit and show
      alterations of consciousness and/or neurological symptoms.

PMID- 14634804
TI  - Detection of enterovirus capsid protein VP1 in myocardium from cases of
      myocarditis or dilated cardiomyopathy by immunohistochemistry: further evidence
      of enterovirus persistence in myocytes.
AB  - The association of enteroviruses with myocardial disease has been investigated
      extensively by molecular biological techniques to detect viral RNA, but remains
      controversial. This retrospective study investigated the involvement of
      enterovirus in myocarditis or dilated cardiomyopathy (DCM) by detection of viral
      antigens in myocardial samples from a new patient series using an optimized
      immunohistochemical technique. Formalin-fixed, paraffin-embedded biopsy, autopsy
      or explanted myocardial tissue samples were obtained from 136 subjects. These
      comprised histologically proven cases of acute fatal myocarditis (n=10), DCM
      (n=89, including 10 patients with healing/borderline myocarditis) and a
      comparison group of samples from 37 unused donor hearts and cases with other
      conditions. A monoclonal antibody 5-D8/1 directed against a conserved, non
      conformational epitope in capsid protein VP1 was employed for broad detection of
      different enterovirus serotypes. Investigations were performed blindly.
      Histological sections from 7 of 10 fatal myocarditis cases, 47 of 89 patients
      (52.8%) with DCM were positive for the viral capsid protein VP1 by
      immunohistochemical staining. Consecutive sections of positive samples were
      negative when the antibody was omitted or replaced with subclass- and
      concentration-matched normal mouse IgG. In contrast, only 3 of 37 samples (8.1%)
      in the comparison group were positive (Yates corrected chi(2)=19.99, P<0.001:
      odds ratio =12.68). VP1 staining was distributed in individual or grouped
      myofibers and localized in the cytoplasm of myocytes. In some cases, VP1 was
      detected in only a few myofibers within an entire section. These results provide
      further evidence of enterovirus involvement in a high proportion of DCM cases and
      demonstrate that VP1 is present in disease stages from acute myocarditis, healing
      myocarditis to end-stage DCM requiring cardiac transplantation, indicating
      translation of viral protein during persistent enterovirus infection.

PMID- 14634805
TI  - Inhibition of HIV-1 infection by monoclonal antibodies to carbohydrates of
      Schistosoma mansoni.
AB  - Patients infected with HIV-1 develop a potent humoral immune response against the
      virus, but HIV-1 primary isolates are remarkably resistant to neutralizing
      antibodies. Considering that the envelope glycoprotein of HIV-1 (gp120/41) is
      heavily glycosylated, we investigated whether anti-carbohydrate antibodies could
      inhibit HIV-1 infection in vitro. We studied the neutralizing activity of three
      monoclonal antibodies (mAbs) raised to carbohydrates of Schistosoma mansoni,
      against seven primary isolates of HIV-1. Assays were performed infecting
      peripheral blood mononuclear cells from normal donors with viral isolates
      previously treated with mAbs. Viral strains used were tropic for the coreceptors
      CCR5, CXCR4, and dual-tropic ones. We found that the anti-glycan mAbs vigorously
      inhibited HIV-1 infection, regardless of the preferential coreceptor usage of the
      isolate, in a dose-response manner. Importantly, five isolates were resistant to
      neutralization by two HIV-1 antibody-positive human sera endowed with potent anti
      HIV-1 inhibitory activity. Our findings suggest that carbohydrates of the HIV-1
      viral envelope may be a target of an effective humoral immune response elicited
      by vaccination.

PMID- 14634806
TI  - Small juxtadrenal cellular schwannoma.

PMID- 14634807
TI  - Mucoepidermoid carcinoma of the breast.
AB  - Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All
      patients were women ranging in age from 29 years to 80 years. As histological
      grading is one of the most important prognostic factors in breast invasive
      carcinomas, MEC was graded using the Auclair et al. [1] grading system specific
      for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely
      employed grading system in breast cancer. It was found that the two different
      grading systems appear to be interchangeable in assessing the grade of MEC of the
      breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate
      (G. 2) and one high grade (G. 3). The cases were studied with
      immunohistochemistry and were found to have the same keratin pattern shown by
      their salivary gland counterpart. It was found that there are more similarities
      than differences between MEC of the breast and of salivary glands.

PMID- 14634808
TI  - Coloring an action: intending to produce color events eliminates the Stroop
      effect.
AB  - The implications of an ideomotor approach to action control were investigated. In
      Experiment 1, participants made manual responses to letter stimuli and they were
      presented with response-contingent color patches, i.e., colored action effects.
      This rendered stimuli of the same color as an action's effect effective primes of
      that action, suggesting that bilateral associations were created between actions
      and the effects they produced. Experiment 2 combined this set-up with a manual
      Stroop task, i.e., participants responded to congruent, neutral, or incongruent
      color-word compounds. Standard Stroop effects were observed in a control group
      without action effects and in a group with target-incompatible action effects,
      but the reaction time Stroop effect was eliminated if actions produced target
      compatible color effects (e.g., blue word --> left key --> blue patch).
      Experiment 3 did not replicate this interaction between target-effect
      compatibility and color-word congruency with color words as action effects, which
      rules out semantically based accounts. Theoretical implications for both action
      effect acquisition and the Stroop effect are discussed. It is suggested that
      learning action effects, the features of which overlap with the target, allows
      and motivates people to recode their actions in ways that make them more stimulus
      compatible. This provides a processing shortcut for translating the relevant
      stimulus into the correct response and, thus, shields processing from the impact
      of competing word distractors.

PMID- 14634809
TI  - Response priming by supraliminal and subliminal action effects.
AB  - Theories assuming an effect-based coding of action predict that motor responses
      become activated by the perception of the responses' sensory effects. In
      accordance with this prediction it was found that responding to a visual target
      is faster and more accurate when the target is briefly preceded by the visual
      effect of the required response. Most importantly, this effect-induced response
      priming was independent of prime perceptibility and it occurred even when the
      prime was not consciously discriminable. Beyond ruling out alternative
      interpretations of earlier induction studies in terms of deliberate response
      biases, this suggests that effect codes evoke their associated motor patterns in
      a highly automatic manner not affording conscious mediation. The results accord
      with a functional dissociation between the consciousness-mediated implementation
      and the consciousness-independent realization of action goals.

PMID- 14634810
TI  - The role of anticipation and intention in the learning of effects of self
      performed actions.
AB  - The anticipative learning model for acquiring action-effect relations states that
      the acquisition of action-effect relations depends on processes that are part of
      action planning, in particular the anticipation of possible effects. Experiment 1
      shows that response planning is indeed crucial for the learning of response
      effects. In this experiment distractors (tones) were presented either during
      response preparation or in the time interval between response execution and the
      presentation of a response effect. Response-effect learning was impaired when the
      distractors were presented during response preparation. The finding is consistent
      with the assumption that the distractors impaired the anticipation of potential
      effects and therefore reduced effect learning. In Experiment 2 all responses had
      two effects. Participants were instructed to produce one of the effects. Under
      this condition, response-effect learning was only found for the instructed
      effect, not for the non-instructed effect. The two experiments thus support the
      view that response-effect learning is selective and depends on the anticipation
      of potential effects during response planning. The results are discussed in terms
      of a model that explains both the learning of response-effect relations and the
      use of these effects for action control within the same theoretical framework.

PMID- 14634811
TI  - Stimulus-set location does not affect orthogonal stimulus-response compatibility.
AB  - In two-choice tasks for which stimuli and responses vary along orthogonal
      dimensions, one stimulus-response mapping typically yields better performance
      than another. For unimanual movement responses, the hand used to respond, hand
      posture (prone or supine), and response eccentricity influence this orthogonal
      stimulus-response compatibility (SRC) effect. All accounts of these phenomena
      attribute them to response-related processes. Two experiments examined whether
      manipulation of stimulus-set position along the dimension on which the stimuli
      varied influences orthogonal SRC in a manner similar to the way that response
      location does. The experiments differed in whether the stimulus dimension was
      vertical and the response dimension horizontal, or vice versa. In both
      experiments, an advantage of mapping up with right and down with left was evident
      for several response modes, and stimulus-set position had no influence on the
      orthogonal SRC effect. The lack of effect of stimulus-set position is in
      agreement with the emphasis that present accounts place on response-related
      processes. We favor a multiple asymmetric codes account, for which the present
      findings imply that the polarity of stimulus codes does not vary across task
      contexts although the polarity of response codes does.

PMID- 14634812
TI  - Asynchronous perception of motion and luminance change.
AB  - Observers were asked to indicate when a target moving on a circular trajectory
      changed its luminance. The judged position of the luminance change was displaced
      from the true position in the direction of motion, indicating differences between
      the times-to-consciousness of motion and luminance change. Motion was processed
      faster than luminance change. The latency difference was more pronounced for a
      small (116-134 ms) than for a large luminance decrement (37 ms). The results show
      that first-order motion is perceived before an accurate representation of
      luminance is available. These findings are consistent with current accounts of
      the flash-lag effect. Two control experiments ruled out that the results were due
      to a general forward tendency. Localization of the target when an auditory signal
      was presented did not produce forward displacement, and the judged onset of
      motion was not shifted in the direction of motion.

PMID- 14634813
TI  - Examining the time course of facilitation and inhibition with simultaneous onset
      and offset cues.
AB  - The experiment conducted examined the effect of simultaneously presented onset
      and offset cues on the orienting of attention in the visual field. Subjects were
      presented with a display that consisted of four placeholder boxes around a
      central fixation point. An onset and an offset cue appeared simultaneously in two
      of the locations, and the other two locations provided a neutral baseline
      condition. Reaction times were measured in a simple target detection task with
      stimulus-onset asynchronies (SOAs) that ranged from 100 ms to 1,000 ms. As
      expected, the onset cue produced early facilitation and later occurring
      inhibition of return (IOR). The offset cue produced significant inhibition at all
      but the earliest SOA. These results suggest that simultaneously presented onset
      and offset cues both capture attention, but that attention is rapidly disengaged
      from the location of the offset cue, resulting in earlier occurring IOR. For the
      onset cues, attention is allocated for a longer period of time, producing the
      typical pattern of early facilitation and later occurring IOR. The differing time
      course of attention at each location may reflect separate facilitatory and
      inhibitory processes, and the priority given to the onset of a stimulus by the
      attentional system.

PMID- 14634814
TI  - Speed-accuracy modulation in case of conflict: the roles of activation and
      inhibition.
AB  - This study investigated how the speed-accuracy balance is modulated by changes in
      the time course of motor activation and inhibition of a primed response.
      Responses and event-related brain potentials were recorded in a paradigm in which
      the first stimulus indicated the correct response with 80% validity. The
      remaining 20% of the trials required no response (no-go) or a response opposite
      to the cued hand (change trials). Subjects were instructed either to balance
      speed and accuracy or to emphasize speed at the cost of accuracy. Analyses of
      error patterns, reaction time distributions and brain potentials show that
      subjects can modulate the amount of activation of the primed response. More
      surprisingly, the engagement of inhibition of the response also varied with the
      speed-accuracy instruction. The results are consistent with a model where the
      frontothalamic loop actively controls both the activation and the inhibition of
      responses, depending on the current task requirements.

PMID- 14634815
TI  - The item-order hypothesis reconsidered: the role of order information in free
      recall.
AB  - According to the item-order approach of free recall, in pure short lists the free
      recall of unrelated items is organized according to their order of presentation
      in the study list. The approach was applied in the present study to experimenter
      performed tasks (EPTs) and subject-performed tasks (SPTs). It claims that EPTs
      provide better serial order information than SPTs. Consequently, free recall of
      EPTs should be more organized along the presentation order of the items than the
      free recall of SPTs. In three experiments, some specific aspects of this approach
      were studied. Firstly, it was demonstrated that serial retrieval is not strongly
      used spontaneously and that its use is overestimated in the literature because it
      is usually evoked by an order reconstruction test which follows free recall
      testing. Secondly, a serial retrieval strategy in free recall can be encouraged
      by explicit instructions. Finally, the present experiments showed that a serial
      output strategy alone does not allow one to predict performance in free recall.
      The implications of these findings for the item-order approach will be discussed.

PMID- 14634816
TI  - The effect of discordant sensory information in graphic production: two distinct
      subject groups.
AB  - The present study investigated the underlying processes used to cope with
      discordant sensory information induced in a mirror-drawing task. Two experiments
      were carried out in which adults copied simple geometrical figures made up of
      either horizontal and vertical segments or oblique segments meeting at a right
      angle in both a normal and a mirror condition. Experiment 1 identified individual
      differences in relation to preferred graphic movement directions; some subjects
      preserved the visual directions that occurred in normal drawing by reversing the
      direction of drawing movements (perceived-direction group), while others
      preserved normal drawing directions that produced reversed visual directions
      (performed-direction group). Experiment 2 was performed to elucidate whether
      these two distinct behaviors resulted from different strategies used to cope with
      visuo-proprioceptive discordances. The main results showed that preference for
      the perceived directions led to longer pauses, slower movement velocity, greater
      movement dysfluency, and greater spatial orientation accuracy. By contrast,
      longer reaction time and greater angular accuracy characterized performance in
      the performed-direction group. These results were interpreted as indicating that
      two distinct information-processing strategies can be used when resolving sensory
      discordance in graphic production.

PMID- 14634818
TI  - Tissue-specific and subcellular localization of phototropin determined by immuno
      blotting.
AB  - Phototropin (phot) is a UV/blue- light receptor mediating phototropic reactions
      of plants as a response to unilateral irradiation. Using an antiserum directed
      against the N-terminal part of Arabidopsis phot1, we show here cross-reaction
      with phototropin from Avena sativa, Eruca sativa, Glycine max, Lepidium sativum,
      Lycopersicon esculentum, Pisum sativum, Sinapis alba, and Zea mays. In all
      investigated plants, blue light irradiation led to a gel mobility shift of
      phototropin corresponding to an apparent increase in size of 2-3 kDa. This
      increase is transient: the apparent size of the phototropin band reverted back to
      the original size in the dark within 60-90 min. The capacity for in vitro
      phosphorylation increased to 350% ( A. sativa) and 200% ( L. sativum) at 90 min
      after a blue light pulse without an increase in the amount of phototropin
      protein. Starting from coleoptile tips of monocots that contained the highest
      concentration of phototropin, we found an exponential decrease in basipetal
      sections of equal size while a linear decrease was determined for dicots in
      basipetal sections starting from the section below the hypocotyl hook. We
      confirmed the membrane association of all phototropin in dark-grown seedlings;
      after a 2-min blue light pulse, however, 20% of phototropin was found in the
      cytosolic fraction and only 80% in the membrane fraction. Both fractions showed
      the gel mobility shift indicating light-dependent autophosphorylation. Detergent
      free solubilization of phototropin with chaotropic reagents was investigated with
      etiolated A. sativa seedlings. Up to 95% of phototropin was solubilized with a
      mixture of sodium bromide and sodium diphosphate, and subsequently subjected to
      affinity purification using Cibachron Blue 3GA-agarose as a dinucleotide
      analogue. Immediately after solubilization, soluble phototropin still showed blue
      light-dependent autophosphorylation but lost its activity within less than 1 h.

PMID- 14634817
TI  - Cotton-fiber germin-like protein. II: Immunolocalization, purification, and
      functional analysis.
AB  - Cotton (Gossypium hirsutum L.) contains a germin-like protein (GLP), GhGLP1, that
      shows tissue-specific accumulation in fiber. The fiber GLP is an oligomeric,
      glycosylated protein with a subunit size of approximately 25.5 kDa. Accumulation
      of GhGLP1 occurs during the period of fiber elongation [4-14 days post-anthesis
      (DPA)]. During early phases of fiber development (2-4 DPA), GhGLP1 localizes to
      cytoplasmic vesicles as shown by confocal immunofluorescent microscopy. In
      slightly older fibers (7-10 DPA), GhGLP1 localizes to the apoplast. In other
      plants, germins and GLPs have been reported to have enzymatic activities
      including oxalate oxidase (OxO), superoxide dismutase, and ADP-glucose
      pyrophosphatase. Cotton fiber extracts did not contain OxO activity, nor did
      intact fibers stain for OxO activity. A four-step purification protocol involving
      ammonium sulfate precipitation of a 1.0 M NaCl extract, ion-exchange
      chromatography on DEAE-Trisacryl M, lectin-affinity chromatography, and gel
      filtration chromatography resulted in electrophoretically pure GhGLP1. While 1.0
      M NaCl extracts from 10-14 DPA fiber contained superoxide dismutase and
      phosphodiesterase activities, GhGLP1 could be separated from both enzyme
      activities by the purification protocol. Although a GLP accumulates in the cotton
      fiber apoplast during cell elongation, the function of this protein in fiber
      growth and development remains unknown.

PMID- 14634819
TI  - The tyrosine kinase Yes regulates actin structure and secretion during pancreatic
      acinar cell damage in rats.
AB  - Acinar cells require a functional apical actin web for secretion. During
      stimulation with supraphysiological concentrations of cholecystokinin (CCK), a
      condition that mimics acute pancreatitis, the actin filaments disintegrate. This
      leads to retention of secretory enzymes and, together with their premature
      activation, results in cell injury. Actin filaments are anchored through membrane
      associated protein complexes that can be regulated through Src-family kinases in
      some model systems. Here we show that the Src-family kinases Yes and Lyn, but not
      Src and Fyn, are expressed in isolated pancreatic acini of Wistar rats. Upon
      stimulation with supramaximal secretory CCK (10(-8) M), Yes became reversibly
      tyrosine-phosphorylated and activated within 2 min. Immunocytochemical and
      subcellular fractionation studies showed reversible redistribution of Yes to the
      apical actin web and to the membrane fraction within 5 min. Coimmunoprecipitation
      demonstrated that Yes forms a complex with the focal adhesion protein Pyk2, which
      increased with CCK stimulation. In functional studies, inhibition of Src-kinase
      activity with PP2 partially reversed actin disintegration and also restored
      amylase secretion. We conclude that Yes participates in the regulation of the
      acinar cell actin, probably by interaction with Pyk2.

PMID- 14634820
TI  - Muscle- and fibre type-specific expression of glucose transporter 4, glycogen
      synthase and glycogen phosphorylase proteins in human skeletal muscle.
AB  - The muscle- and fibre type-specific expression of skeletal muscle glucose
      transporter 4 (GLUT4), glycogen synthase (GS) and glycogen phosphorylase (GP) was
      investigated in six young male subjects. Single muscle fibres were dissected from
      vastus lateralis (VL), soleus (SO) and triceps brachii (TB) muscle biopsy
      samples. On the basis of myosin heavy chain (MHC) expression, fibres were pooled
      into three groups (MHC I, MHC IIA and MHC IIX) and the GLUT4, GS and GP content
      of 15-40 pooled fibres determined using SDS-PAGE and immunological detection. In
      VL, the GLUT4 content in the pooled muscle fibres expressing MHC I was
      approximately 33% higher ( P<0.05) than in fibres expressing MHC IIA or IIX.
      There was no difference in GLUT4 content between fibres expressing MHC IIA or
      IIX, nor were there any differences in GS and GP content between any of the fibre
      types. In SO, there was no difference in GLUT4, GS and GP between fibres
      expressing MHC I or IIA. No fibres expressing type IIX were detected. In TB,
      fibres expressing MHC IIA and IIX had significantly ( P<0.05) more GP (66% and 55
      % in MHC IIA and MHCIIX, respectively) than those expressing MHC I, whilst there
      was no difference in GP between MHC IIA and MHC IIX fibres. The GLUT4 and the GS
      content was similar in fibres expressing MHC I, IIA and IIX in the TB. Our data
      directly demonstrate that some proteins, like GLUT4 and GP, are expressed in a
      fibre type-specific manner in some, but not all, muscles, whilst other proteins,
      like GS, are not. In human skeletal muscle the GLUT4, GS and GP content thus
      seems to be related primarily to factors other than the fibre type as defined by
      the expression of contractile protein. These findings imply that it is not
      possible to generalize fibre type-dependent protein expression on the basis of
      biopsies from only one muscle.

PMID- 14634821
TI  - Ryanodine receptors in peritoneal mast cells: possible role in the modulation of
      exocytotic activity.
AB  - Previous studies have shown that ryanodine in low concentrations and caffeine
      increase intracellular [Ca(2+)] in the absence of external Ca(2+), suggesting
      Ca(2+) release from intracellular stores through ryanodine receptors (RyR). In
      the present study we employed amperometry to examine the effect of RyR agonists
      and antagonists on serotonin release elicited with compound 48/80 (10 micro
      g/ml). Ryanodine (1 micro M) or, similarly, 20 mM caffeine, in the absence of
      external Ca(2+), enhanced the amperometric response to compound 48/80 and all the
      individual amperometric spike parameters. Ryanodine (50 micro M), dantrolene (20
      micro M) and tetracaine (50 micro M), putative antagonists of the RyR, attenuated
      the amperometric response significantly, decreasing the number and frequency of
      events as well as their amplitude. This is the first demonstration that Ca(2+)
      availability from RyR-operated Ca(2+) sources may contribute to the modulation of
      secretory activity in mast cells, affecting not only the cellular exocytotic
      response, but also the characteristics of single amperometric events.
      Immunocytochemical labelling, using a monoclonal RyR antibody, confirmed the
      presence of RyR in this preparation.

PMID- 14634822
TI  - Melatonin reduces noradrenaline-induced vasoconstriction in the uterine artery of
      pregnant hooded seals (Cystophora cristata).
AB  - In pregnant seals the dive-associated constriction of the uterine artery is
      inhibited for unknown reasons. The seal fetus has an extremely large and active
      pineal gland, not found in any other mammals. We have investigated if the pineal
      hormone melatonin affects fetal blood supply during diving. Using isolated ring
      segments of the uterine artery from pregnant hooded seals (Cystophora cristata),
      we measured the change in isometric tension caused by noradrenaline (NA) with and
      without physiological concentrations of melatonin. Melatonin alone had no effects
      while NA increased the tension in a dose-dependent manner. The NA-induced tension
      was about 70% reduced by melatonin, but was completely recovered after washout of
      melatonin. These results indicate that the large and active pineal gland of the
      fetal seal may be involved in upholding maternal uterine blood flow during
      diving.

PMID- 14634823
TI  - Tyrosine kinase inhibition differentially regulates heterologously expressed HCN
      channels.
AB  - The HCN ion channel subunit gene family encodes hyperpolarization-activated
      cation channels that are permeable to Na(+) and K(+). There are four members of
      this channel family, three of which, HCN1, HCN2, and HCN4, are expressed in the
      heart. Current evidence suggests that the HCN ion channel subunit family is the
      molecular correlate of the alpha subunit of the cardiac pacemaker current i(f).
      Our previous work has shown that HCN4 is the dominant isoform expressed in the
      rabbit sinoatrial (SA) node and that changes in tyrosine phosphorylation, either
      by kinase inhibition or growth factor activation, lead to changes in rabbit SA
      node i(f) conductance with no change in voltage dependence. In the present study
      we investigate the actions of genistein, a tyrosine kinase inhibitor, on
      heterologously expressed HCN currents in Xenopus oocytes. Genistein had no effect
      on HCN1-induced currents, but reduced whole-cell currents induced by HCN2 or HCN4
      and slowed activation kinetics at voltages near the midpoint of activation. In
      the case of HCN2 there was also a negative shift in the voltage dependence of
      activation that accompanies the current reduction. We have shown previously that
      HCN2 is the dominant isoform expressed in rat ventricular myocytes. The above
      results predict that genistein should reduce i(f) in the rat ventricle and cause
      a negative shift of voltage dependence and kinetics of activation. We tested this
      hypothesis by studying the effects of genistein on isolated rat ventricular
      myocytes. Genistein significantly reduced i(f) current density (pA/pF) (control:
      12.2+/-1.8; genistein: 3.5+/-0.5; washout: 7.7+/-0.8; n=10), and caused a
      negative shift of the midpoint of activation by 14 mV (-133+/-1 mV for genistein
      and -119+/-1 mV for washout, n=7) with no change in slope factor. Our results
      thus suggest that i(f) in the heart and i(f)-like currents in other tissues can
      be regulated differentially by tyrosine phosphorylation based on isoform
      expression patterns.

PMID- 14634824
TI  - Voluntary drive-dependent changes in vastus lateralis motor unit firing rates
      during a sustained isometric contraction at 50% of maximum knee extension force.
AB  - The purpose of the present study was to relate the expected inter-subject
      variability in voluntary drive of the knee extensor muscles during a sustained
      isometric contraction to the changes in firing rates of single motor units.
      Voluntary activation, as established with superimposed electrical stimulation was
      high (range: 91-99%, n=8) during a short maximal contraction, but was lower
      (range: 69-100%) in most subjects at the point of force failure during a
      sustained (49.1+/-10.1 s) fatiguing contraction at 50% of maximum force. On a
      different experimental day the firing behaviour of 27 single motor units was
      recorded with wire electrodes in the vastus lateralis muscle, 24 of which could
      be monitored from the time of recruitment to the point of force failure (53.6+/
      9.8 s). Motor unit firing behaviour differed considerably among subjects. During
      the second half of the sustained, fatiguing contraction the changes in firing
      rate firing rate variability of early recruited units ranged from -10% to +100%
      and from -50% to +160% respectively among subjects. There were significant
      positive linear relations between voluntary activation, on the one hand, and
      rectified surface electromyogram (rsEMG, r=0.82), the changes in motor unit
      firing rate ( r=0.49) and firing rate variability ( r=0.50) towards the point of
      force failure on the other. The present data suggest that differences in
      voluntary drive that appear among subjects during fatigue may be an important
      determinant of motor unit firing behaviour.

PMID- 14634825
TI  - Prospective evaluation of diagnostic modalities in suspected acute appendicitis.
AB  - BACKGROUND: The aim of this prospective study was to evaluate different
      diagnostic modalities routinely employed in a district hospital. METHOD: Four
      hundred subsequent patients presenting with acute abdominal pain were included
      over a period of 18 months. Patient characteristics, diagnostic work-up,
      intraoperative findings, histology and clinical outcome were documented. Rectal
      temperature, white cell count (WCC), C-reactive protein (CRP), ultrasonography
      (US) and Ohmann score were analysed with relation to diagnostic value. RESULTS:
      Negative appendicectomy rate and negative laparotomy rate on the day of admission
      were 22% and 21%, respectively. Sensitivity was highest for WCC and CRP (0.82 and
      0.85) but US showed highest values for specificity (0.92), accuracy (0.85) and
      odds ratio (13.06). No patient with an Ohmann score below 6.5 suffered from acute
      appendicitis. With regard to different levels of training in US, experienced
      surgeons and radiologists had best values for specificity (1.00 and 0.98) and
      accuracy (0.90 and 0.94). Surprisingly, less-experienced sonographers also
      achieved good results with regard to specificity (up to 0.96) and positive
      predictive value (up to 0.89). CONCLUSION: Diagnostic accuracy of acute
      appendicitis remains insufficient, with an unacceptable high rate of unnecessary
      operations. Only the promotion of routine ultrasonography might contribute to an
      improvement in the near future.

PMID- 14634826
TI  - Gastrointestinal profile of symptomatic athletes at rest and during physical
      exercise.
AB  - Some athletes suffer from exercise-induced gastrointestinal (GI) disturbances. We
      developed a profile of GI parameters in 10 symptomatic and 10 asymptomatic
      athletes both at rest and during exercise. Exercise included 90 min of cycling
      and running at 70% of maximal power. We measured oesophageal motility, gastro
      oesophageal reflux, gastric emptying, orocaecal transit time (OCTT), intestinal
      permeability and intestinal glucose absorption. During cycling the number and
      duration of refluxes were increased, whereas gastric emptying showed no
      differences between rest, cycling and running. The OCTT was increased in the
      running trial, compared to rest (P=0.005). Also, intestinal permeability was
      higher in the running trial, compared to rest (P=0.008). There were no
      differences in intestinal glucose absorption between rest and exercise. Compared
      with asymptomatic athletes the symptomatic subjects had a higher intestinal
      permeability (P=0.001), more reflux episodes (P=0.03) and a longer duration of
      reflux (P<0.05) during cycling. No differences were observed at rest. In
      conclusion, there is no difference in GI profile between symptomatic and
      asymptomatic athletes at rest. During exercise, symptomatic subjects have a
      longer OCTT and a higher intestinal permeability, which is more pronounced during
      running than during cycling.

PMID- 14634827
TI  - Human body surface area: a theoretical approach.
AB  - Knowledge of the human body surface area has important applications in medical
      practice, garment design, and other engineering sizing. Therefore, it is not
      surprising that several expressions correlating body surface area with direct
      measurements of body mass and length have been reported in the literature. In the
      present study, based on the assumption that the exterior shape of the human body
      is the result of convex and concave deformations from a basic cylinder, we derive
      a theoretical equation minimizing body surface area (BSA) at a fixed volume (V):
      BSA=(9pi VL)(0.5), where L is the reference length of the body. Assuming a body
      density value of 1,000 kg.m(-3), the equation becomes BSA=(BM.BH/35.37)(0.5),
      where BSA is in square meters, BM is the body mass in kilograms, and BH is the
      body height in meters. BSA values calculated by means of this equation fall
      within +/-7% of the values obtained by means of the equations available in the
      literature, in the range of BSA from children to adults. It is also suggested
      that the above equation, which is obtained by minimizing the outer body surface
      at a fixed volume, implies a fundamental relation set by the geometrical
      constraints governing the growth and the development of the human body.

PMID- 14634828
TI  - Measuring intraocular pressure with the Pulsair 3000 and Rebound tonometers in
      elderly patients without an anesthetic.
AB  - PURPOSE: To evaluate the utility of the new Rebound tonometer for measuring
      intraocular pressure (IOP) in an unanesthetized eye; to test patient tolerance,
      measurement time, and accuracy compared with the Pulsair 3000 tonometer. METHODS:
      IOP was measured with the Rebound tonometer and the Pulsair 3000 tonometer
      without an anesthetic in 131 residents of two Finnish nursing homes. The
      measurement time and possible pain or discomfort experienced by the inhabitants
      was recorded. RESULTS: The mean differences in IOP readings between the two
      tonometers were 0.31 mmHg, SD 2.45 mmHg for the right eyes and 0.36 mmHg, SD 2.17
      mmHg for the left eyes (P=0.28, multivariate analysis). The correlation constants
      between the tonometers were 0.84 (right eyes) and 0.80 (left eyes). The Pulsair
      3000 caused more discomfort than the Rebound tonometer (36% vs 15%, P=0.01). With
      the Pulsair, 85%, and with the Rebound tonometer, 95% of the patients felt no
      pain ( P= 0.14). Measurement of both eyes with the Rebound tonometer took less
      time (55+/-22 s vs 138+/-55 s, P<0.001). The mean difference was 82 s and the 95%
      confidence interval of the difference was 66-98 s. CONCLUSION: Measurement of IOP
      with the Rebound tonometer without an anesthetic is a rapid and well-tolerated
      procedure. IOP readings of the two tonometers were within +/-1 mmHg in 52.5% of
      the measurements and within +/-2 mmHg in 71.7% of the measurements.

PMID- 14634829
TI  - Expression of estrogen receptor alpha and 17beta-hydroxysteroid dehydrogenase 4
      in the ciliary body.
AB  - PURPOSE: To investigate the expression and distribution of estrogen receptor
      alpha (ERalpha) and 17beta-hydroxysteroid dehydrogenase 4 (HSD4) in bovine and
      monkey ciliary body. METHODS: Immunohistochemical study was employed to
      investigate the expression of ERalpha and 17beta-HSD4. To detect ERalpha and
      17beta-HSD4 transcripts, reverse transcription-polymerase chain reaction (RT-PCR)
      was used. RESULTS: In bovine and monkey ciliary body, the staining of the anti
      ERalpha antibody was distributed in nonpigmented epithelium, and was not
      detectable in pigmented epithelium. Vessels in the stroma were also stained. The
      expression of 17beta-HSD4 was observed in nonpigmented and pigmented epithelium.
      RT-PCR revealed that the transcripts of ERalpha and 17beta-HSD4 were expressed in
      monkey ciliary body. CONCLUSIONS: This study provides evidence for the presence
      of ERalpha and 17beta- HSD4 in the ciliary body. The presence of ERalpha and
      17beta-HSD4 suggests that estrogen may have important functions in the ciliary
      body.

PMID- 14634830
TI  - Airbag contact in traffic accidents: DNA detection to determine the driver
      identity.
AB  - A total of 34 deployed driver and passenger airbags from altogether 20 vehicles
      after frontal collisions were investigated. In 80% of the airbags possible
      biological traces could be located with an alternative light source (ALS,
      Polilight) at a wavelength of 450-470 nm. These traces were swabbed, a part of
      them additionally cut and subjected to DNA analysis, which led to comparable
      SGMplus profiles in about 60%. In the 20% of the airbags on which no possible
      biological traces could be located, the whole surfaces were swabbed. In these
      cases subsequent DNA profiling mostly led to non-interpretable results. For the
      evaluation and interpretation of the data, buccal swab samples provided by
      drivers and co-drivers were analysed. The results and conclusions from DNA
      analyses and the declarations from the involved passengers were always
      concordant. Thus, molecular biological analysis of deployed airbags can help to
      determine the occupants positions within a vehicle (driver or passenger status)
      at the time of impact.

PMID- 14634831
TI  - Sudden death due to a haemoglobin variant.
AB  - A previous healthy 35-year-old man was found dead in his truck. Shortly before
      death he merely complained of influenza-like symptoms. The histological
      examination revealed evidence of a massive accumulation of sickle cells in
      smaller blood vessels. After molecular genetic analysis, the preliminary
      diagnosis of "sickle cell disease" was finally changed to the diagnosis of a
      sickle cell trait. It is presumed that an epileptic attack which also has to be
      considered as a concurring cause of death, precipitated sickling of the
      erythrocytes and led to a fatal sickle cell crisis.

PMID- 14634832
TI  - Fatal cerebro-renal oxalosis after appendectomy.
AB  - A case of a 24-year-old male with fatal cerebro-renal oxalosis assumed to be due
      to infusions of the sugar surrogate xylitol after appendectomy is reported. The
      diagnosis was established only after intensive histological investigations
      following the autopsy. The clinical picture was characterized by an acute
      seizure, coma and renal failure 2 days after the first xylitol infusion. Death
      occurred due to cerebral dysregulation as a very rare complication after
      parenteral administration of xylitol. Subendothelial double refractive calcium
      oxalate crystals were found in the walls of cerebral blood vessels, in particular
      in the stem ganglion regions and in the cortical renal tubules. The most common
      type of primary oxalosis was excluded by sequencing analysis. The young age, the
      minor surgical intervention and the otherwise unremarkable history are special
      features of this case. Since the genetic background of xylitol intolerance is
      still unclear, it is suggested that it should be banned as a sugar surrogate in
      clinical practice.

PMID- 14634833
TI  - Five highly informative X-chromosomal STRs in Koreans.
AB  - The five X-chromosomal short tandem repeats (STRs) GATA172D05, HPRTB, DXS8377,
      DXS101 and HumARA were analyzed in 150 males and 150 females from Korea. Markers
      were amplified in a quadruplex and a monoplex PCR reaction with fluorescently
      labeled primers. For accurate and reproducible STR typing, sequenced allelic
      ladders were constructed and a Genotyper macro was programmed. Some differences
      were found on comparing the allele frequencies of Koreans with those of other
      populations in DXS8377, DXS101 and HumARA. The forensic efficiency parameters
      showed that the five X-linked STRs are highly informative for forensic
      application in Koreans.

PMID- 14634834
TI  - Production and characterization of the milk-clotting protease of Myxococcus
      xanthus strain 422.
AB  - The cheese industry is seeking novel sources of enzymes for cheese production.
      Microbial rennets have several advantages over animal rennets. (1) They are easy
      to generate and purify and do not rely on the availability of animal material.
      (2) The production of microbial clotting enzymes may be improved by
      biotechnological techniques. In this work, the biochemical characterization of a
      novel milk-clotting extracellular enzyme from Myxococcus xanthus strain 422 and a
      preliminary evaluation of its cheese-producing ability are reported. Strain 422
      was selected from four M. xanthus strains as the best producer of extracellular
      milk-clotting activity, based on both its enzyme yield and specific milk-clotting
      activity, which also afforded lower titration values than enzymes from the three
      other M. xanthus strains. The active milk-clotting enzyme from M. xanthus strain
      422 is a true milk-clotting enzyme with a molecular mass of 40 kDa and a pI of
      5.0. Highest milk-clotting activity was at pH 6 and 37 degrees C. The enzyme was
      completely inactivated by heating for 12 min at 65 degrees C. The crude enzyme
      preparation was resolved by anion-exchange chromatography into two active
      fractions that were tested in cheese production assays of compositional (dry
      matter, fat content, fat content/dry-matter ratio, and moisture-non-fat content)
      and physicochemical properties (firmness, tensile strength, pH and Aw) of the
      milk curds obtained. Purified protein fraction II exhibited a significantly
      higher milk-clotting ability than either protein fraction I or a total protein
      extract, underlining the potential usefulness of M. xanthus strain 422 as a
      source of rennet for cheese production.

PMID- 14634835
TI  - Proximal superficial temporal artery to proximal middle cerebral artery bypass
      using a radial artery graft: an anatomic approach.
AB  - We present the use of radial artery graft for bypass of the proximal superficial
      temporal artery to the proximal middle cerebral artery. Six adult cadaver sites
      were used bilaterally. After apterional incision, 2x2-cm minicraniectomy was
      performed which began 2 cm behind the zygomatic process of the frontal bone. The
      superficial temporal artery was transsected before exposing the zygomatico
      orbital artery branch. The proximal side of the radial artery graft was
      anastomosed end-to-end to the proximal superficial temporal artery and the distal
      side end-to-side to the proximal middle cerebral artery. The mean calibers of the
      proximal superficial temporal artery and largest trunk of the middle cerebral
      artery were 2.25+/-0.35 mm and 2.3+/-0.3 mm, respectively. The average graft
      length was 85+/-5.5 mm. We conclude that such bypasses are simpler than proximal
      middle cerebral artery revascularization using long vein grafts. This method
      proves that the caliber of the proximal superficial temporal artery is more
      suited to providing sufficient flow than the distal superficial temporal artery,
      and the graft is short. Such bypasses to the middle cerebral artery may be an
      alternative to those from the distal superficial temporal artery or extracranial
      carotid artery.

PMID- 14634836
TI  - Anatomy of the clinoidal region with special emphasis on the caroticoclinoid
      foramen and interclinoid osseous bridge in a recent Turkish population.
AB  - In this study we present the incidence of caroticoclinoid foramen and
      interclinoid osseous bridge and some topographic aspects regarding the clinoidal
      internal carotid artery (ICA) in a recent Turkish population to provide a guide
      for neurosurgeons in any surgical approach, especially to the cavernous sinus.
      One hundred nineteen adult dry skulls and 52 adult cadaveric heads were used for
      this purpose. Caroticoclinoid foramen and the interclinoid osseous bridge were
      divided into three types based on the classification of Keyers [13].
      Caroticoclinoid foramen was observed in 35.67% of the specimens, unilaterally in
      23.98%, and bilaterally in 11.69%. The complete-type caroticoclinoid foramen was
      observed in 4.09% of the specimens, the contact type in 4.68%, and the incomplete
      type in 14.91%. Transverse diameter of the foramen was 5.32+/-0.52 mm for the
      incomplete type. The incidence of interclinoid osseous bridge was 8.18%. The
      middle clinoid process was prominent in 15.12% of cases and rudimental in 13.23%.
      The mean distance between the proximal and distal dural rings of the clinoidal
      ICA was 4.51+/-0.44 mm, and mean diameter of the distal ring was 5.25+/-0.59 mm.
      Right-left differences were assessed for each parameter, and populational
      differences are discussed.

PMID- 14634838
TI  - Allele frequencies of single nucleotide polymorphisms (SNPs) in 40 candidate
      genes for gene-environment studies on cancer: data from population-based Japanese
      random samples.
AB  - Knowledge of genetic polymorphisms in gene-environment studies may contribute to
      more accurate identification of avoidable risks and to developing tailor-made
      preventative measures. The aim of this study was to describe the allele
      frequencies of single nucleotide polymorphisms (SNPs) of select genes, which may
      be included in future gene-environment studies on cancer in Japan. SNP typing was
      performed on middle-aged Japanese men randomly selected from the general
      population in five areas of Japan. We genotyped and calculated allele frequencies
      of 153 SNPs located on 40 genes: CYP1A1, CYP1B1, CYP2C9, CYP2C19, CYP2E1,
      CYP17A1, CYP19A1, AHR, ESR1, ESR2, ERRRG, PGR, EPHX1, EPHX2, HSD17B2, HSD17B3,
      GSTM2, GSTM3, GSTT2, GSTP1, NAT1, NAT2, COMT, ADH1A, ADH1B, ADH1C, ALDH2, NOS2A,
      NOS3, IL1A, IL1B, OGG1, NUDT1 [MTH1], DRD2, DRD3, DRD4, SLC6A4, NR3C1 [GCCR],
      MTHFR, and NQO1. In the present study, the Japanese allele frequencies were
      verified by using nationwide population samples.

PMID- 14634839
TI  - Morgagni hernia: repair with a mesh using laparoscopic surgery.
AB  - The aim of this study is to present two patients diagnosed with diaphragmatic
      Morgagni hernia and treated by repairing the hernia defect with a mesh by
      laparoscopic surgery. We describe the placement of a double-layer mesh anchored
      with helicoidal staples to repair the hernia defect using laparoscopic surgery.
      Laparoscopic surgery allows repair of these defects whilst avoiding the
      disadvantages of a major laparotomy or a thoracotomy. The existence of double
      layer meshes that can be placed in contact with the abdominal viscera allows the
      defect to be closed safely and without tension.

PMID- 14634840
TI  - Traumatic abdominal hernia associated with large bowel strangulation: case report
      and review of the literature.
AB  - A rare case of traumatic rupture of the abdominal wall with ventral herniation
      and strangulation of the right colon is presented. The defect was detected by
      computed tomography on admission. The patient was operated on 3 days after
      injury, and irreversible ischaemia of the right colon was found. Right
      hemicolectomy was performed. The pathogenesis and treatment of this complication
      is discussed.

PMID- 14634841
TI  - Preperitoneal repair for recurrent inguinal hernia: laparoscopic and open
      approach.
AB  - BACKGROUND: The aim of this study was to investigate the outcome of preperitoneal
      repair using laparoscopic (TEP) and open (OPM) approach in recurrent inguinal
      hernia. METHODS: We performed a prospective controlled nonrandomized clinical
      study in 188 patients with 207 recurrent inguinal hernias over a period of 5
      years. TEP repair was employed for 86 repairs, and OPM was used in 121
      procedures. The main outcome measurements were: recurrence rate, operating time,
      hospital stay, and postoperative complications. RESULTS: There were three
      recurrences (1.7%). Two in the OPM group (1.8%) and one (1.3%) in the TEP group [
      P=NS (not significant)]. The TEP procedure was faster than OPM for unilateral
      repair (40.8 vs 46.3 min) (P<0.001). Postoperative complications were more
      frequent in the OPM group (23.9%) than the TEP group (13.9%) ( P=NS). Hospital
      stay was significantly shorter in the TEP group (1.2 vs 3.9 days) (P<0.001).
      CONCLUSIONS: Preperitoneal approach (open or laparoscopic) seems to be a good
      option in recurrent inguinal hernia when these procedures are done by experienced
      surgeons.

PMID- 14634842
TI  - Effect of prosthetic material on adhesion formation after laparoscopic ventral
      hernia repair in a porcine model.
AB  - Intraperitoneal placement of prosthetic mesh causes adhesion formation after
      laparoscopic incisional hernia repair. A prosthesis that prevents or reduces
      adhesion formation is desirable. In this study, 21 pigs were randomized to
      receive laparoscopic placement of plain polypropylene mesh (PPM), expanded
      polytetrafluoroethylene (ePTFE), or polypropylene coated on one side with a
      bioresorbable adhesion barrier (PPM/HA/CMC). The animals were sacrificed after 28
      days and evaluated for adhesion formation. Mean area of adhesion formation was
      14% (SD+/-15) in the PPM/HA/CMC group, 40% (SD+/-17) in the PPM group, and 41%
      (SD+/-39) in the ePTFE group. The difference between PPM/HA/CMC and PPM was
      significant ( P=0.013). A new visceral layer of mesothelium was present in seven
      out of seven PPM/HA/CMC cases, six out of seven PPM cases, and two out of seven
      ePTFE cases. Thus, laparoscopic placement of PPM/HA/CMC reduces adhesion
      formation compared to other mesh types used for laparoscopic ventral hernia
      repairs.

PMID- 14634843
TI  - Inguinal hernia: challenging the traditional indication for surgery in
      asymptomatic patients.
AB  - BACKGROUND: It is generally accepted that most inguinal hernias should be
      operated on electively in order to avoid the high morbidity and mortality
      associated with incarceration and small bowel obstruction. The present study
      reassesses the indication for surgery in asymptomatic inguinal hernia patients.
      METHODS: We analyzed profiles, separately, for elective and emergency inguinal
      herniorrhaphies and compared the morbidity and mortality rates. RESULTS: Two
      hundred randomly selected elective hernia repairs were compared with 67
      incarcerated cases. Postoperative complications were more common following
      emergency (23.9%) than elective repair (10.5%); however, in both groups, minor
      complications predominated. The mortality rate in the incarcerated group (6%) was
      clearly linked with a high preoperative American Society of Anesthesiologists
      (ASA) score. A bowel resection rate of 4.5% was found in the incarcerated cases,
      which was not correlated with mortality. CONCLUSIONS: Patients with asymptomatic
      inguinal hernia and unfavorable medical conditions should be recommended an
      elective repair, preferably under local anesthesia, to avoid the high mortality
      associated with an emergency operation.

PMID- 14634844
TI  - Anatomical considerations for surgery of the anterolateral abdominal wall.
AB  - Closure of large incisional hernias with the Components Separation Method (CSM)
      could be explained by medial-caudal rotation of the internal and transverse
      oblique muscles around their centres of origin. In eight human cadavers, the CSM
      was performed, and translation of the rectus abdominis muscle was measured. Mean
      unilateral translation of the rectus abdominis in the lateral-medial direction
      measured 2.2, 3.7, and 3.5 cm. This was 2.7, 4.5, and 4.0 cm after release of the
      posterior rectus sheath. Mean translation in a caudal direction was 0.5 cm, but
      seven cadavers showed a mean translation of 1 cm of the uppermost measuring point
      in a cranial direction. The hypothesis that rotation of separate tissue layers of
      the abdominal wall largely accounts for the translation effect of the CSM must be
      rejected. Release of the external oblique muscle produces more benefit to
      abdominal wall closure than release of the posterior rectus sheath.

PMID- 14634845
TI  - Incidence of incisional hernia following vertical banded gastroplasty.
AB  - BACKGROUND: Our aim was to determine which patient-related factors influence the
      incidence of incisional hernia after vertical banded gastroplasty for morbid
      obesity. METHODS: We reviewed the medical records of 80 morbidly obese patients
      operated on between 1986 and 1993. All the operations were performed by only one
      surgeon, and the midline laparotomy was closed by means of continuous polyglactin
      910 suture. Statistical analysis was performed using the Fisher exact test, and
      significance was assigned for values of P<0.05. RESULTS: Incidence of incisional
      hernia in: obese 24%, superobese 51% ( P=0.0165), men 40%, women 34% ( P=0.7671),
      age<50 33%, age>50 50% ( P=0.3137), nondiabetics 31%, diabetics 66% ( P=0.0610),
      no wound infection 34%, wound infection 37% ( P>0.9999), no anemia 31%, anemia
      50% ( P=0.1675), no vomiting 39%, vomiting 32% ( P=0.6350). CONCLUSION: The only
      patient-related factor that significantly influences the incidence of incisional
      hernia in morbidly obese patients is body mass index.

PMID- 14634846
TI  - Conformational preferences of 1,4,7-trithiacyclononane: a molecular mechanics and
      density functional theory study.
AB  - Conformational preferences of 1,4,7-trithiacyclononane were studied using a
      highly efficient sampling technique based on local nonstochastic deformations and
      the MM2(91) force field. The results show that conformers that the molecule
      adopts in the crystal state were found to be low-energy conformers (LECs) within
      5 kcal mol(-1) of the global minimum. A conformation with C1 symmetry was the
      global minimum and the C3 and C2 conformations were calculated to be 0.03 and
      1.78 kcal mol(-1) higher in energy, respectively. The structures were further
      minimized using Density Functional Theory (DFT) calculations with two different
      functionals. The C2 and the C1 conformations were found to be LECs with the C3
      conformation more than 4.0 kcal mol(-1) above the global minimum. The relative
      energies and structural ordering obtained using the BP86 functional are in
      agreement with the previously reported relative energies calculated using second
      order Moller-Plesset (MP2) ab initio calculations. With the energy ordering being
      dependent on the molecular mechanics force field used, the approach of MM-->DFT
      (searching exhaustively the available conformational space at the MM level
      followed by generating the energy ordering through DFT calculations) appears to
      be appropriate for thiacrown ethers.

PMID- 14634847
TI  - Density functional and docking studies of retinoids for cancer treatment.
AB  - The retinoic acid receptor (RAR) and retinoid X receptor (RXR) are members of the
      nuclear receptor superfamily. The ligand-binding domain contains the ligand
      dependent activation function. The isotypes RARalpha,beta and gamma are distinct
      pharmacological targets for retinoids involved in the treatment of various
      cancers and skin diseases. There is thus considerable interest in synthetic
      retinoids with isotype selectivity and reduced side effects. In this work we have
      focused on the retinoid acid receptor and three of its panagonists. We have
      carried out density functional geometry optimizations at the B3LYP/6-31G* level,
      computed two types of atomic charges and also electrostatic potentials. A docking
      program was used to investigate the interactions between the receptor and the
      three ligands. A theoretically more potent inhibitor, which was obtained by
      modifying one of the retinoic acids investigated, is proposed.

PMID- 14634848
TI  - Structure-based method for analyzing protein-protein interfaces.
AB  - Hydrogen bond, hydrophobic and vdW interactions are the three major non-covalent
      interactions at protein-protein interfaces. We have developed a method that uses
      only these properties to describe interactions between proteins, which can
      qualitatively estimate the individual contribution of each interfacial residue to
      the binding and gives the results in a graphic display way. This method has been
      applied to analyze alanine mutation data at protein-protein interfaces. A dataset
      containing 13 protein-protein complexes with 250 alanine mutations of interfacial
      residues has been tested. For the 75 hot-spot residues (deltadelta G > or = 1.5
      kcal mol(-1)), 66 can be predicted correctly with a success rate of 88%. In order
      to test the tolerance of this method to conformational changes upon binding, we
      utilize a set of 26 complexes with one or both of their components available in
      the unbound form. The difference of key residues exported by the program is 11%
      between the results using complexed proteins and those from unbound ones. As this
      method gives the characteristics of the binding partner for a particular protein,
      in-depth studies on protein-protein recognition can be carried out. Furthermore,
      this method can be used to compare the difference between protein-protein
      interactions and look for correlated mutation.

PMID- 14634850
TI  - Computer-assisted posterior instrumentation of the cervical and cervico-thoracic
      spine.
AB  - Posterior instrumentation of the cervical spine has become increasingly popular
      in recent years. Dissatisfaction with lateral mass fixation, especially at the
      cervico-thoracic junction, has led spine surgeons to use pedicle screws. The
      improved biomechanical stability of pedicle screws and transarticular C1/2 screws
      allows for shorter instrumentations and improves the repositioning possibilities.
      Nevertheless, there are potential risks of iatrogenic damage to the spinal cord,
      nerve roots or the vertebral artery with both techniques. Therefore, the aim of
      this study was to evaluate whether C1/2 transarticular screws and transpedicular
      screws can be applied safely and with high accuracy in the cervical spine and the
      cervico-thoracic junction using a computer-assisted surgery system (CAS system).
      Posterior instrumentation was performed using the Brainlab VectorVision System
      (BrainLAB, Heimstetten, Germany) in 19 patients. Surface matching was used for
      registration. We placed 22 transarticular screws C1/2, 31 cervical pedicle
      screws, 10 high thoracic pedicle screws and one lateral mass screw C1. The screw
      position was evaluated postoperatively using CT with multiplanar reconstruction
      in the screw axis of each screw. None of the transarticular screws or pedicle
      screws was significantly (>2 mm) misplaced and no screw-related injury to
      vascular, neurogenic or bony structures was observed. No screw revision was
      necessary. The mean operation time was 144 min (90-240 min) and the mean blood
      loss was 234 ml (50-800 ml). C1/2 transarticular screws, as well as
      transpedicular screws in the cervical spine and the cervico-thoracic junction,
      can be applied safely and with high accuracy using a CAS system. Computer
      assisted instrumentation is recommended especially for pedicle screws at C3-C6.

PMID- 14634852
TI  - Intraoperative urodynamics in spinal cord surgery: a study of feasibility.
AB  - Intraoperative monitoring (IOM) of bladder function in spinal cord surgery is a
      challenging task due to vegetative influences, multilevel innervation and
      numerous supraspinal modulating factors. Despite routine use of urodynamics in
      neurosurgery for implantation of bladder stimulators or denervation of nerve
      fibres in spastic reflex bladders, application of IOM in patients with spinal
      cord tumours or tethered-cord syndrome is not widespread. Combining urodynamics
      with sphincter electromyography (EMG) in IOM enables identification of bladder
      efferents responsible for contraction and continence. We monitored four patients
      with ependymoma of the Cauda equina, one patient with tethered-cord syndrome and
      two patients with cervical intramedullary tumours. In all patients undergoing
      operations of the Cauda equina, identification of bladder efferents responsible
      for detrusor contraction was possible. There was good correlation between
      preoperative bladder dysfunction, preoperative urodynamics and intraoperative
      pressure increase by bladder contraction or latency between stimulation and
      contraction. This method proved unsuitable for intramedullary tumours where no
      contraction of the bladder could be observed while stimulating the spinal cord.
      Intraoperative monitoring of urodynamics is an effective tool for identifying
      bladder efferents in the Cauda equina. Intraoperative conclusions on bladder
      dysfunction through registration of pressure increase and latency are possible.

PMID- 14634853
TI  - Conjoined lumbosacral nerve roots: current aspects of diagnosis.
AB  - Conjoined lumbosacral nerve roots (CLNR) are the most common anomalies involving
      the lumbar nerve structures which can be one of the origins of failed back
      syndromes. They can cause sciatica even without the presence of a additional
      compressive impingement (such as disc herniation, spondylolisthesis or lateral
      recess stenosis), and often congenital lumbosacral spine anomalies (such as bony
      defects) are present at the "conjoined sheaths". This congenital anomaly has been
      reported in 14% of cadaver studies, but myelographic or computed tomographic
      studies have revealed an incidence of approximately 4% only. Diagnostic methods
      such as magnetic resonance imaging (MRI) are helpful for determination of the
      exact anatomical relations in this context. We present five typical cases of
      conjoined nerve roots observed during a 1 year period, equivalent to 6% of our
      out-patients without a history of surgical treatment on the lumbar spine. In all
      cases with suspicious radiological findings MRI or lumbar myelography combined
      with CT and multiplanar reconstructions is recommended.

PMID- 14634854
TI  - Thoracolumbar fracture stabilization: comparative biomechanical evaluation of a
      new video-assisted implantable system.
AB  - Minimally invasive techniques for spinal surgery are becoming more widespread as
      improved technologies are developed. Stabilization plays an important role in
      fracture treatment, but appropriate instrumentation systems for endoscopic
      circumstances are lacking. Therefore a new thoracoscopically implantable
      stabilization system for thoracolumbar fracture treatment was developed and its
      biomechanical in vitro properties were compared. In a biomechanical in vitro
      study, burst fracture stabilization was simulated and anterior short fixation
      devices were tested under load with pure moments to evaluate the biomechanical
      stabilizing characteristics of the new system in comparison with a currently
      available system. With interbody graft and fixation the new system demonstrated
      higher stabilizing effects in flexion/extension and lateral bending and restored
      axial stability beyond the intact spine, as well as having comparable or improved
      effects compared with the current system. Because of this biomechanical
      characterization a clinical trial is warranted; the usefulness of the new system
      has already been demonstrated in 45 patients in our department and more than 300
      cases in a multicenter study which is currently under way.

PMID- 14634855
TI  - Acute phase response in patients undergoing lumbar spinal surgery: modulation by
      perioperative treatment with naproxen and famotidine.
AB  - In orthopaedic surgery, perioperative administration of non-steroidal anti
      inflammatory drugs has been shown to reduce postoperative pain and analgesic
      consumption. In addition, preoperative administration of ibuprofen has proved to
      reduce interleukin-6 (IL-6) release, while that of ranitidine reduced
      postoperative IL-6-induced C-reactive protein synthesis in patients undergoing
      abdominal surgery. However, it has not been established whether the preoperative
      administration of both types of drugs may reduced the postoperative inflammatory
      reaction after instrumented spinal surgery. Accordingly, our objective was to
      investigate the effects of preoperative treatment with naproxen plus famotidine
      on the postoperative systemic inflammatory reaction in patients undergoing
      instrumented lumbar spinal surgery. Forty consecutive patients scheduled for
      elective instrumented spinal fusion were alternately assigned to receive either
      naproxen (500 mg/day, p.o.) plus famotidine (40 mg/day, p.o.) for 7 days before
      operation, or no adjuvant treatment. Haematological parameters, acute phase
      proteins, complement fractions, immunoglobulins and cytokines were determined 7
      days and immediately before surgery, and on days 0, 1, 2 and 7 after surgery.
      Haematological parameters, clinical data, duration of surgery, blood loss,
      perioperative blood transfusion and postoperative complications were similar in
      the two groups, although pretreated patients showed lower increases in body
      temperature and required less analgesic medication. Compared with preoperative
      levels, IL-6 levels were significantly increased postoperatively in all patients
      with no differences between groups. C-reactive protein, alpha(1)-acid
      glycoprotein and haptoglobin levels were also significantly increased
      postoperatively in all patients; however, they were significantly lower in
      pretreated patients. In conclusion, perioperative treatment with naproxen plus
      famotidine was well tolerated and reduced the acute phase response after
      instrumented spinal surgery. However, further research is needed to determine the
      best dose and timing of preoperative treatment administration, and to correlate
      these changes with long-term clinical results.

PMID- 14634857
TI  - The early-stage ectomycorrhizal Thelephoroid fungal sp. is competitive and
      effective on Afzelia africana Sm. in nursery conditions in Senegal.
AB  - This study was conducted to evaluate the competitiveness and effectiveness of
      Thelephoroid fungal sp. ORS.XM002 against native ectomycorrhizal fungal species
      colonizing potted Afzelia africana seedlings during 3 months of growth in
      different forest soils collected from under mature trees. Using morphotyping and
      restriction fragment length polymorphism (RFLP) analysis of the nuclear rDNA
      internal transcribed spacer (ITS), we were able to distinguish the introduced
      Thelephoroid fungal sp. ORS.XM002 among native ectomycorrhizal fungal species
      that form ectomycorrhizae in A. africana seedlings. The morphotype (MT) of the
      introduced fungus showed some color variation, with a shift from light- to dark
      brown observed from younger to older mycorrhizal tips. We were able to
      differentiate the ITS type xm002 of the introduced fungus from the 14 ITS-RFLP
      types characterizing the 9 native MT that occurred in forest soils. The frequency
      of ITS type xm002 ranged from 40% to 49% depending on the forest soil used, and
      was always higher than those of ITS types from native dark-brown MT that occurred
      in inoculated seedlings 3 months after inoculation. We considered Thelephoroid
      fungal sp. ORS.XM002 to be responsible for stimulation of mycorrhizal
      colonization of inoculated A. africana seedlings when compared with control
      seedlings in forest soils. This fungus appeared to be more effective in
      increasing the root dry weight of A. africana seedlings. To identify the unknown
      introduced fungal species and native MT, we sequenced the ML5/ML6 region of the
      mitochondrial large subunit rRNA. Sequence analysis showed that these fungi
      belong to three ML5/ML6 groups closely related to the Cortinarioid, Thelephoroid,
      and Sclerodermataceous taxa. The molecular evidence for the persistence of
      Thelephoroid fungal sp. ORS.XM002 despite competition from native fungi argues in
      favor of using this fungus with A. africana in nursery soil conditions in
      Senegal.

PMID- 14634858
TI  - Lupus nephritis in childhood: a review of 53 patients followed at a single
      center.
AB  - We retrospectively evaluated the clinical and histopathological features,
      treatment modalities, and outcome of 53 children and adolescents with biopsy
      proven lupus nephritis (LN), followed between September 1983 and September 2001.
      The mean age (+/-SD) at the time of diagnosis of systemic lupus erythematosus
      (SLE) was 12.9+/-2.6 years and the mean follow-up from the time of biopsy was
      4.8+/-3.4 years. At the time of biopsy, all 53 patients had proteinuria, 21 (40%)
      had nephrotic syndrome, and 14 (26%) had impaired renal function. Class IV
      nephritis, observed in 34 (64%) patients, was the most frequent histopathology on
      initial renal biopsy. The patients with class IV LN had a significant tendency to
      develop hypertension ( P=0.04) and nephrotic syndrome ( P=0.027), and a lower
      mean glomerular filtration rate ( P=0.000). Based on the renal histopathology and
      clinical presentation, patients were treated with corticosteroids alone or
      combined with azathioprine or with intravenous cyclophosphamide. Plasmapheresis
      or cyclosporine was used in 4 and 1 patient, respectively. Follow-up biopsies,
      performed in 13 patients, showed no change in 6 patients, were progressive in 4,
      and regressive in 3. On final clinical evaluation, renal disease was in complete
      or partial remission in 42 of 53 patients (80%), 4 had clinically active disease
      but with normal renal function, and 7 (13%), all with WHO class IV LN, were
      classified as having an adverse outcome, i.e., either preterminal (2) or terminal
      (4) renal failure or death (1). Five-year kidney and patient survival rates from
      the time of biopsy to the endpoints of terminal renal failure or death were 88.6%
      and 98.1%, respectively, in the whole group, and 82.4% and 97.1%, respectively,
      in the WHO class IV group. Nephrotic syndrome and class IV nephritis at initial
      biopsy were the only parameters significantly associated with adverse outcome in
      our study group. There was no association with gender, age, hypertension,
      impaired renal function, anemia, increased morphological index scores, and
      treatment modalities. We conclude that clinical and histopathological features of
      LN and treatment regimens in our study do not differ markedly from those in most
      pediatric series. However, the 5-year kidney and patient survival rates are among
      the best reported in recent pediatric series. The prognosis of LN is primarily
      dependent on the histopathological lesions.

PMID- 14634859
TI  - Parathyroid hormone levels in pubertal uremic adolescents treated with growth
      hormone.
AB  - We have previously described severe hyperparathyroidism during the pubertal
      growth spurt in three uremic adolescents treated with recombinant human growth
      hormone (rhGH). Here we investigate the possible role of puberty in the genesis
      of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data
      from 67 uremic patients treated with rhGH from five Italian pediatric nephrology
      centers were retrospectively recorded every 3 months starting 1 year before rhGH
      administration. The mean (+/-SD) rhGH treatment observation period was 19.9+/-5.9
      months. The mean age at the start of rhGH treatment was 8.3+/-3.6 years. Of the
      67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment
      and 12 of these 15 progressed to pubertal stage 3. The relative increase in
      parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal
      [1.95, 95% confidence interval (CI) 1.43-2.66] than in prepubertal patients
      (1.19, 95% CI 1.01-1.40). Increases in PTH levels were significantly different
      between the two groups (Delta=1.64, 95% CI 1.16-3.19, P=0.007). Multiple
      regression analysis showed an inverse correlation between PTH and calcium levels
      and a positive correlation between PTH and pubertal stage 3. There was no
      correlation with phosphate levels and calcitriol dosage. In conclusion, these
      results suggest that in uremic adolescents treated with rhGH puberty may
      influence PTH levels.

PMID- 14634860
TI  - Intermittent versus maintenance iron therapy in children on hemodialysis: a
      randomized study.
AB  - In patients with renal anemia, iron therapy can be administered intermittently or
      regularly at a low dose. We performed a randomized clinical trial in pediatric
      patients with end-stage renal failure on hemodialysis and absolute or functional
      iron deficiency. The study group received maintenance iron therapy according to
      the ferritin serum levels and the control group received intermittent 10-weekly
      doses. Success was defined as stabilization of ferritin levels between 100 and
      800 microg/l and transferrin saturation (TSAT) between 20% and 50%, in addition
      to an increase in the hemoglobin level. The major reason for exclusion was iron
      overload. The study group received 6 mg/kg per month of parenteral iron [95%
      confidence interval (CI) 3.3-8.8] and the control group 14.4 mg/kg per month (95%
      CI 12-16.8) ( P<0.001). After 4 months of treatment, ferritin levels increased to
      66 microg/l (95% CI 69-200) in the study group and to 334 microg/l (95% CI 145
      522) in the control group ( P=0.009). Maintenance therapy and intermittent weekly
      doses were successful in 73% and 38%, respectively. After 3 months of treatment,
      hemoglobin levels increased to 10 g/dl, with no difference between the groups.
      However, in the control group the increase in hemoglobin levels was unsustained,
      and 3 patients needed transfusion. Patients in the control group had a higher
      risk of iron overload than patients in the study group (70% vs. 19%). Thus, the
      regimen based on assessment of serum ferritin levels was more efficient than the
      intermittent regimen because it increased and maintained the hemoglobin levels
      with lower iron doses and a lower risk of iron overload.

PMID- 14634861
TI  - Genetics of hereditary disorders of magnesium homeostasis.
AB  - Magnesium plays an essential role in many biochemical and physiological
      processes. Homeostasis of magnesium is tightly regulated and depends on the
      balance between intestinal absorption and renal excretion. During the last
      decades, various hereditary disorders of magnesium handling have been clinically
      characterized and genetic studies in affected individuals have led to the
      identification of some molecular components of cellular magnesium transport. In
      addition to these hereditary forms of magnesium deficiency, recent studies have
      revealed a high prevalence of latent hypomagnesemia in the general population.
      This finding is of special interest in view of the association between
      hypomagnesemia and common chronic diseases such as diabetes, coronary heart
      disease, hypertension, and asthma. However, valuable methods for the diagnosis of
      body and tissue magnesium deficiency are still lacking. This review focuses on
      clinical and genetic aspects of hereditary disorders of magnesium homeostasis. We
      will review primary defects of epithelial magnesium transport, disorders
      associated with defects in Ca(2+)/ Mg(2+) sensing, as well as diseases
      characterized by renal salt wasting and hypokalemic alkalosis, with special
      emphasis on disturbed magnesium homeostasis.

PMID- 14634862
TI  - Antiproliferative effect of fluvastatin and thiazolidinedione in mesangial cells
      of diabetic rats.
AB  - Treatment with hydroxymethylglutaryl coenzyme A reductase inhibitors and
      thiazolidinedione derivatives may prevent the development of diabetic
      nephropathy. The precise mechanisms of the beneficial effects of these agents in
      mesangial cells are uncertain. We cultured mesangial cells from Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes mellitus. The
      effects of fluvastatin and/or troglitazone on DNA synthesis were determined.
      Fluvastatin in combination with troglitazone markedly inhibited DNA synthesis and
      induced apoptosis in mesangial cells from OLETF rats. Combined therapy with
      fluvastatin and thiazolidinedione derivatives may be effective for suppression of
      mesangial cell proliferation in the early phase of diabetes, thereby possibly
      slowing the evolution of diabetic glomerulopathy.

PMID- 14634863
TI  - Fluid overload and acute renal failure in pediatric stem cell transplant
      patients.
AB  - Acute renal failure (ARF) with fluid overload (FO) occurs often in stem cell
      transplant (SCT) recipients. We have previously demonstrated that an increased
      percentage of FO prior to the initiation of continuous renal replacement therapy
      (CRRT) is associated with mortality in children with ARF. Based on these data, we
      devised a protocol for the prevention of FO in SCT patients with ARF. SCT
      patients with ARF and 5% FO were started on furosemide and low-dose dopamine. To
      allow for nutrition, medication, and blood product administration, RRT was
      initiated for patients with > or =10% FO. There were 272 patients who received
      allogeneic SCT from 1999 to 2002. Of these, medical records of 26 SCT patients
      with a first episode of oliguric ARF were reviewed. The mean patient age was 13+/
      5 years (range 2-23.5 years). Mean days to ARF after SCT were 28+/-29 days (range
      2-90 days). Of the 26 patients, 11 (42%) survived an initial ARF episode. All 11
      survivors either maintained <10% FO during their course or re-attained <10% FO
      with RRT treatment. Of the 15 non-survivors, 6 had <10% FO at the time of death.
      Of 14 patients who received RRT, 4 (29%) survived. Mechanical ventilation and
      pediatric risk of mortality score > or =10 at the time of admission to the
      intensive care unit were associated with lower survival ( P<0.05). The use of one
      or more pressors, the presence of graft-versus-host disease, and septic shock
      were not correlated with survival. Our data demonstrate that maintenance of
      euvolemia ( <10% FO) is critical but not sufficient for survival in SCT patients
      with ARF, as all non-euvolemic patients died. We suggest that aggressive use of
      diuretics and early initiation of RRT to prevent worsening of FO may improve the
      survival of SCT patients.

PMID- 14634864
TI  - Henoch-Schonlein purpura nephritis: course of disease and efficacy of
      cyclophosphamide.
AB  - Nephritis in Henoch-Schonlein purpura (HSP) is the primary cause of morbidity and
      mortality. Although many therapeutic regimens have been reported to be effective,
      no therapy has been shown in a controlled trial to be beneficial. Fifty-six
      patients with histopathologically severe HSP nephritis were randomized to receive
      supportive therapy with or without cyclophosphamide, 90 mg/m(2)/day for 42 days.
      Patients were classified according to status at final follow-up: Fully Recovered
      48.2%, Persistent Abnormalities 39.3%, or ESRD/Death 12.5%. There were no
      differences in onset data or outcome between the two trial groups or in outcome
      between trial and 23 non-trial patients followed concurrently. Therefore, data
      from trial and non-trial patients were combined for further analysis. There was
      no correlation between outcome and age, blood pressure, serum total protein, or
      serum albumin. Although rates of proteinuria did not correlate with outcome, all
      those with progression to ESRD had nephrotic levels of proteinuria at onset. Only
      five of 28 patients with nephrotic levels of proteinuria and severe onset
      histopathology recovered fully. No patient with crescents in 50% or more of
      glomeruli went on to full recovery. Recurrence of non-renal symptoms did not
      correlate with outcome. Nephrotic syndrome, decreased GFR, and more severe
      histopathology at onset, as well as persistence of urinary abnormalities for
      several years, are ominous signs.

PMID- 14634865
TI  - Acute renal failure in a patient with phosphofructokinase deficiency.
AB  - A 16-year-old Caucasian girl was admitted to hospital with acute renal failure
      and hemolytic anemia due to rhabdomyolysis following a 3-km walk. (31)P-magnetic
      resonance spectroscopy provided characteristic spectra of type VII glycogen
      storage disease (phosphofructokinase deficiency).

PMID- 14634866
TI  - Efficacy of losartan in the treatment of erythrocytosis in a young adult with
      CRF.

PMID- 14634867
TI  - Proteome analysis of rice tissues by two-dimensional electrophoresis: an approach
      to the investigation of gibberellin regulated proteins.
AB  - Protein databases constructed using high-resolution two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) were used to explore the proteome
      expressed in various rice tissues. Proteins from leaf sheath, root, and cultured
      suspension cells were systematically analyzed using 2D-PAGE, mass spectrometry
      and Edman sequencing, followed by database searching. In all, 79 of the 431 spots
      detected by 2D-PAGE in the leaf sheath, 73 of the 508 spots in the root and 140
      of the 962 spots in the cultured suspension cells could be identified. Protein
      lists were constructed for each tissue and used to investigate the effects of
      gibberellin (GA) treatment. In the leaf sheath, root and cultured suspension
      cells, 8, 21, and 14 of the identified proteins, respectively, were regulated by
      GA. These proteins included polypeptides involved in general metabolism, energy
      production, transcriptional regulation and signal transduction in the leaf
      sheath; in metabolism and defense in the root; and in metabolism, energy
      production, cell growth, defense and signal transduction in the cultured
      suspension cells. These results indicate that the proteome databases assembled in
      these studies will be useful for the rapid assessment of changes in protein
      content in specific tissues, and that proteins regulated by GA may play a
      significant role in tissue growth.

PMID- 14634868
TI  - Complete nucleotide sequence and analysis of pPSR1 (72,601 bp), a pPT23A-family
      plasmid from Pseudomonas syringae pv. syringae A2.
AB  - Plasmid pPSR1 is a conjugative plasmid originally isolated from Pseudomonas
      syringae pv. syringae A2, and is a member of the recently described pPT23A
      plasmid family. We have determined the complete sequence of pPSR1 and found the
      plasmid to be 72,601 bp in length, encoding 55 ORFs. Putative functions were
      assigned to 49 ORFs; of these, 24 (49.0%) are involved in plasmid replication,
      maintenance or conjugation, 17 (34.7%) have roles in virulence or ecological
      fitness, and eight (16.3%) encode transposase functions as part of mobile
      elements. pPSR1 carries the effector gene orf34, the mutagenic DNA repair operon
      rulAB which confers tolerance to ultraviolet radiation, and two genes for methyl
      accepting chemotaxis proteins, one of which was located within the novel
      transposon Tn 5395. The streptomycin resistance transposon Tn 5393a, which
      carries a strA-strB determinant, was found inserted immediately downstream of the
      pPSR1 repA gene. Functional analysis of the replication region of pPSR1 indicated
      that the repA gene and flanking upstream and downstream sequences are required
      for autonomous replication in P. syringae. Hybridization analyses of the
      distribution of 11 of the pPSR1 ORFs indicated that many of the ecologically
      important ORFs were confined to the pathovar P. syringae pv. syringae -either to
      strains from the local population from which pPSR1 was originally isolated, or
      strains from a worldwide collection. Conjugative transfer genes and a gene
      encoding a transcriptional regulator were more widely distributed among several
      P. syringae pathovars. The sequence analysis of pPSR1 suggests that pPT23A-family
      plasmids evolve by accumulating genes that are important for host-pathogen
      interactions or growth on plant hosts, which are incorporated onto a conserved
      backbone encoding conjugation and stability determinants.

PMID- 14634870
TI  - [German centre for quality in medicine prelude to red-tapism of state-controlled
      medicine?].

PMID- 14634869
TI  - MAX, a novel retrotransposon of the BEL-Pao family, is nested within the Bari1
      cluster at the heterochromatic h39 region of chromosome 2 in Drosophila
      melanogaster.
AB  - A homogeneous array of 80 tandem repeats of the Bari1 transposon is located in
      the pericentromeric h39 region of chromosome 2 of Drosophila melanogaster. Here,
      we report that the Bari1 cluster is interrupted by an 8556-bp insertion. DNA
      sequencing and database searches identified this insertion as a previously
      unannotated retrotransposon that we have named MAX. MAX possesses two ORFs; ORF1
      putatively encodes a polyprotein comprising GAG and RT domains, while ORF2 could
      encode a 288-amino acid protein of unknown function. Alignment with the RT
      domains of known LTR retrotransposons shows that MAX belongs to the BEL-Pao
      family, which remarkable for its widespread presence in different taxa, including
      lower chordates. We have analyzed the distribution of MAX elements within
      representative species of the Sophophora subgroup and found that they are
      restricted to the species of the melanogaster complex, where they are heavily
      represented in the heterochromatin of all autosomes and on the Y chromosome.

PMID- 14634871
TI  - [Third-party funding and industrial sponsoring].
AB  - Due to sensational publications, media-effective proceedings and not least due to
      personal involvement in many cases the medical profession became aware of the
      potential criminal significance of third-party funding and industrial sponsoring
      in hospitals. It started with the so-called Heart-Valve-Affair
      ("Herzklappenskandal") in 1994. Since then, insecurity prevails which was further
      nourished by a new series of legal proceedings in spring 2002. Industrial
      sponsoring has been practised in hospitals for a long time. Research work at
      universities and colleges would hardly be possible without third-party funding,
      which is accepted de lege lata according to section sign 25 of the German
      Hochschulrahmengesetz (framework law on universities and colleges). In view of
      the course of action of the criminal prosecution authorities the question came up
      which precautions must be taken with regard to grants by the medical
      pharmaceutical industry to avoid consequences from the point of view of criminal
      law.[nl]There are various facts and circumstances in relation with these
      benefits, such as providing financing of educational training, payments related
      to the participation in congresses, speaker's fees, consultancy agreements,
      clinical tests and application evaluation, provision of equipment and staff as
      well as providing financing thereof, donations to medical facilities and so
      called Fordervereine (supporting associations), benefits for research projects,
      etc.

PMID- 14634872
TI  - [Medical informatics in obstetrics and gynecology - the actual challenge?].
AB  - There is common agreement about the importance of information management systems
      in obstetrics and gynecology. Those systems are necessary tools for medical
      quality management and are essential for the actual preparation for the age of
      the "diagnosis related groups" that will be introduced in Germany next year.
      Nevertheless there are only small scientifically activities to improve
      information management systems and to evaluate their performance. Great efforts
      are necessary to develop new features and not to loose the conflict between the
      needs of the physicians and their patients and the needs and demands of hospital
      administrative authorities.

PMID- 14634873
TI  - [Information technology in gynecological oncology today].
AB  - Information technology has been integrated in gynecological oncology treatment.
      Therefore, new software has been established in hospitals and out-patient
      clinics. A German law concerning data collection in oncology has attempted to
      unify different strategies. All intentions to establish new documentation systems
      for tumor diseases need a standardized basic data set. Nevertheless, local
      governmental health organizations are not yet prepared to implement a global
      information system such as prenatal and perinatal care databases. Financial
      support and political work is therefore needed.

PMID- 14634874
TI  - [Cumulus cell apoptosis as a predictor for oocyte quality in artificial
      reproduction technique].
AB  - OBJECTIVE: To be able to predict the success of ART reliable tests for
      determining the quality of the oocytes are necessary. Apart from a vague
      morphologic assessment via microscopy a direct analysis of the oocyte quality is
      not possible. Because of the very close relation between the oocyte and the
      cumulus cells the analysis of the cumulus cells might give sufficient information
      on the oocyte quality. In this study we correlate the apoptotic activity of
      cumulus cells to the outcome of fertilized oocytes after Intracytoplasmic Sperm
      Injection (ICSI). MATERIAL AND METHODS: 246 cumulus-oocyte-complexes from
      patients undergoing infertility treatment with the ICSI procedure were
      individually collected. The comet assay was used to determine the proportion of
      apoptotic cells within the cumulus population of each oocyte and correlated with
      oocyte fertilization and oocyte quality as well as with pregnancy outcome in 86
      patients. RESULTS: We were able to show that high quality embryos correlate to a
      low rate of apoptotic cells in their corresponding cumuli. Differences regarding
      the pregnancy outcome were statistically not significant. CONCLUSIONS: Our
      results on cumulus cell apoptosis and embryo quality confirm other publications.
      To arrive at statistically proven criteria for the further development of single
      oocytes an increase in the number of analyzed patients is necessary.

PMID- 14634875
TI  - [Estrogen-dependent neoplasia - what is the significance of estradiol
      metabolites].
AB  - Estradiol can be metabolized to substances eliciting different, partly opposite
      effects even at low concentrations as shown in own investigations, e. g.,
      regarding (anti)angiogenic actions. Specific anticancerogenic effects are
      ascribed to 2-hydroxyestrone and particularly 2-methoxyestradiol. In contrast,
      16alpha-hydroxyestrone and the 4-hydroxyestrogens may be genotoxic under certain
      circumstances. Furthermore there are indications that endogenous production of
      proliferation-stimulating metabolites is raised in some cancers. Especially the
      urinary excretion of 2-hydroxyestrone to 16alpha-hydroxyestrone was investigated
      showing in own and other clinical studies a lower ratio in postmenopausal women
      with breast cancer. Research is ongoing inasfar the determination of estradiol
      metabolites also in blood or directly in the breast tissue by means of sensitive
      laboratory methods may allow predictive statements. However, it has be to
      consider that estradiol metabolism can be influenced by external factors such as
      nutrition, smoking, sports and drugs such as L-thyroxine and H2-antagonists. We
      were able to demonstrate that estradiol metabolism during estradiol treatment
      depends on the application mode and might be differently influenced by addition
      of the various progestins. Whether the investigation of gene polymorphism of
      enzymes, which are involved in estradiol metabolism, may be helpful for the
      assessment or treatment of risk patients, to our opinion needs further research.

PMID- 14634876
TI  - [Retrospectively experiencing the menopause in Germany and in Papua New Guinea: a
      comparative report].
AB  - INTRODUCTION: The objective of this study was to examine the experience of
      menopause in postmenopausal women from Germany and in postmenopausal women from
      Papua New Guinea. METHODS: Experience of menopause were assessed by formation of
      symptom groups (e. g. hot flushes, cardiac or sleeping trouble, depression,
      touchiness, drop in performance, vaginal dryness, painful joints or muscles),
      following the Menopause Rating Scale (MRS). Apart from the translated English
      version a questionaire in Pidgin English was offered. Questions about positive
      and negative experience of menopause and the acceptance of hormonal replacement
      therapy were included. Statistical analysis was performed both descriptively and
      for the group analyses the Chi-squared-test and the Mann Whitney's U test.
      RESULTS: 40 postmenopausal German women and 41 postmenopausal women from Papua
      New Guinea were asked about their experience of menopause. The German women were
      58.7 years old (range from 52 to 62) and had two children on average (range from
      0 to 4). 87.7 % had experience of symptoms. In Papua New Guinea mean age was 55.2
      years (range from 48 to 70), parity six (range from 2 to 12). 76.9 % had
      experience of symptoms. There were significant intercultural differences between
      the experience of depressive mood, general drop of performance, sexual experience
      and the vaginal dryness and we found no significant intercultural differences
      between the experiences of hot flushes, cardiac trouble, sleeping trouble,
      nervousness and urological symptoms. 50 % of the German women take hormonal
      replacement therapy and nobody of Papua New Guinea. CONCLUSION: The experience of
      menopause as seen in the developed countries does not exist in the developing
      countries. The perception about illness and well-being are formed by culturally
      produced patterns.

PMID- 14634877
TI  - [Editorial: severe brain injuries].

PMID- 14634878
TI  - Stereotactic aspiration and fibrinolysis of spontaneous supratentorial
      intracerebral hematomas versus conservative treatment: a matched-pair study.
AB  - OBJECTIVES: Since introduction of stereotactic aspiration and fibrinolysis into
      the treatment of deep-seated intracerebral hematomas by Hondo and Matsumoto 1984
      this method has become widely used, and satisfactory morphological results are
      achieved. Nevertheless, whether the outcome is improved has not yet been
      investigated. MATERIAL AND METHOD: 17 patients with spontaneous intracerebral
      hematomas have been treated surgically; after angiographic exclusion of a
      vascular malformation stereotactic aspiration and fibrinolysis with 3 mg rTPA was
      performed. Between 1992 and 1995 104 patients were treated conservatively
      according to best medical treatment. From this group "matched pairs" with the
      surgical patients were set up concurring in primary (consciousness, size and
      location of the hematoma) and secondary parameters (age, sex, ventricular
      hemorrhage). Endpoint of the study was the Glasgow outcome score (GOS) six months
      after treatment. Data were analyzed statistically and p < 0.05 was considered
      significant. RESULTS: In respect of primary parameters complete concurrence and
      regarding secondary parameters far-reaching concurrence was achieved. In no
      parameter the surgical and conservative group were significantly different from
      each other. Six months after the ictus no significant difference between surgical
      and conservative treatment concerning GOS could be established. CONCLUSION: These
      results indicate that patients do not benefit from stereotactic aspiration and
      fibrinolysis of putamenal hematomas. For a final treatment recommendation a
      prospective randomised trial is required.

PMID- 14634879
TI  - Pitfalls in surgery of meningeomas of the free tentorial edge.
AB  - Clinical experiences from 15 meningeomas located on the free edge of the
      tentorium are reported. Unexpected findings and complications found in five
      patients are presented in detail: Despite successful removal without
      postoperative morbidity after a presigmoid approach the preoperative loss of
      function of the ophthalmic nerve may cause increasing keratitis, which may result
      in blindness over the years after surgery. Before a presigmoid approach is
      performed, angiography or magnetic resonance angiography is advised, because the
      patient may have only one sigmoid sinus on the tumor side. An acute subdural
      hematoma as a complication of surgery may not only occur after, but also during
      surgery with the patient in the semi-sitting position. When a space occupying
      tumor of the tentorium is discovered, there may be an additional spinal one. If
      total removal of an extensive tumor of the free edge of the tentorium appears too
      hazardous, a two-stage strategy with a one year interval may lead to success.

PMID- 14634880
TI  - [Possibilities for cost reduction of implants in spinal surgery].
AB  - OBJECTIVE: To evaluate the possibilities for cost reduction in spinal surgery by
      analysing implant costs and the efficiency of each type of implant. MATERIALS AND
      METHODS: The costs of spinal implant methods, as well as Halo-vest for
      craniocervical, cervical, thoracic, lumbar spine are summarised according to an
      analysis of price lists from 2001 and 2002. The different methods were
      additionally evaluated with regard to the scientifically-based treatment
      efficiency. All prices above 100 euro were rounded up to the closest 50 euro. For
      the implants, a literature research was performed. The scientific papers were
      divided into groups according to their level of evidence (I a -IV), and then
      further subdivided into comparable and non-comparable categories. RESULTS:
      Craniocervical: Halo-vest 1,700-2,500 euro, odontoidscrew 100-250 euro, plate
      1,300 euro, wire 20-250 euro; plate-wire-, rod-wire- or rod-screw systems 400
      1,800 euro, clamps 1,200 euro, Cervical: placeholder 20-500 euro, vertebral body
      replacement 400-1,300 euro, plate 75-450 euro; rod- or plate-screw systems 900
      1,700 euro; Thoracic/lumbar: plate/rod-systems 1,000-2,800 euro, vertebral body
      replacement 500-1,300 euro, internal fixateur 800-2,500 euro, cages 600-1,500
      euro. For none of the implant methods were comparable scientific clinical
      publications found with a high levels of evidence (I a-I b). CONCLUSIONS: Costs
      can be reduced through a more thorough investigation and corresponding choice of
      implant method. The cost-benefit analysis of new spinal implants must be
      considered more with regard to the evidence-based spinal surgery. In order to
      sufficiently evaluate the different treatment methods, future multicenter
      controlled comparable studies and meta-analyses must be undertaken.

PMID- 14634881
TI  - Frameless stereotactic brain biopsy procedures using the Stealth Station:
      indications, accuracy and results.
AB  - This study presents the results of 57 stereotactic brain biopsies using a
      frameless neuronavigation system, the Stealth Station. The supratentorial lesions
      had a mean diameter of 33 mm and a mean distance of 32 mm from the entry point at
      brain surface. In all cases the stereotactic procedure was planned in the
      preoperative 3-D magnetic resonance data set. In seven cases additional data for
      identification of eloquent brain areas was integrated from magnetoencephalography
      or functional magnetic resonance imaging. During surgery the samples were sent to
      neuropathological examination and the operation completed after the confirmation
      of pathological tissue. Using this method, in 56 cases a pathological tissue was
      obtained and a diagnostic yield of 98% was achieved. In two cases (3.5%) a new
      neurological deficit remained (hemiparesis and visual field deficit). The mean
      operation time was 92 minutes including examination of frozen sections. The
      results of our series demonstrate, that frameless stereotactic systems can also
      be reliably applied for biopsy of supratentorial lesions larger than 15 mm.
      Frameless stereotaxy in combination with intraoperative pathological confirmation
      is a safe and reliable method for stereotactic brain biopsy with a diagnostic
      yield comparable to frame-based stereotaxy.

PMID- 14634882
TI  - Decompressive craniectomy in severe brain injury.
AB  - OBJECT: The goal of this study was to evaluate the therapeutic role of
      decompressive craniectomy in severe brain injury. METHODS AND RESULTS: Between
      1996 and 1998 we treated 87 patients with severe brain injury (GCS 3-8) in our
      department. In 70 cases follow up data could be obtained. Mean age was 49 years
      (range 1-79). Initial CT scans of all patients demonstrated diffuse brain injury
      with generalised brain swelling and/or mass lesion. In 51 of these patients uni
      (n=40)- or bilateral (n=11) decompressive craniectomy was performed initially or
      secondarily after failure of standard treatment. In a retrospective analysis we
      performed statistical tests of the follow-up group. The mortality rate did not
      show a significant difference between the two treatment groups (p=0.802) with a
      slight advantage for the decompression. The log-rank-test demonstrated a non
      significant improvement of the survival time for decompressed patients (p=0.632).
      Secondary decompression showed a significantly better survival rate and time
      compared to primary decompression. In all 7 pediatric cases (1-16 yrs) we
      performed craniectomy. 2 of them died immediately post emergency operation, 5
      survived with good outcome (1 LOF). CONCLUSIONS: A slight, but non-significant
      benefit could be demonstrated after decompressive craniectomy in the whole
      patient population. In young patients decompression seems to have a more positive
      influence on outcome and survival.

PMID- 14634883
TI  - Brucella diskitis mimicking herniation without spondylitis; MRI findings.
AB  - A case of isolated brucella disk infection mimicking fragmented disk herniation
      is presented. MRI studies were performed two times in 6 months, both of which did
      not show any signs of spondylitis. Since brucella infections are seen along with
      spondylitis, this case has attracted our attention. We focused on radiological
      findings in this pure brucella disk infection.

PMID- 14634885
TI  - [Is surgery necessary in every case of cholesteatoma?].

PMID- 14634886
TI  - [Cognitive therapy for chronic tinnitus - current gold standard].

PMID- 14634887
TI  - [Developments in the treatment of neurinomas of the acoustic nerve].

PMID- 14634888
TI  - [Tonsillotomy versus tonsillectomy].

PMID- 14634889
TI  - [Phoniatry and ENT on: dagnostic and therapeutic problems with organic voice
      disorders].

PMID- 14634890
TI  - [Indications for imaging techniques].

PMID- 14634891
TI  - [Modern management of bleeding disorders and haemorrhage in otorhinolaryngology].
AB  - BACKGROUND: Bleeding disorders and haemorrhages are recognized as common and
      serious problems in otorhinolaryngology. Over the past decade a number of
      innovative technologies and therapeutical options have been established to
      improve the management of them. The aim of this paper is to present diagnostical
      and therapeutical concepts proved to be medically effective and economically
      acceptable and to review the international literature. METHODS: Bleeding
      disorders observed over a period of 10 years were analysed retrospectively to
      determine their prevalence and causes in otorhinolaryngology. Selected cases were
      used to illustrate both the efficacy and the limits of modern therapeutical
      options. A medico-economical evaluation of preoperative hemostaseological tests
      was carried out. RESULTS: Activated partial thromboplastin time (aPTT), Quick's
      prothrombin time combined with a detailed bleeding history were found to be
      optimal parameters to screen most of the haemostaseological defects. The
      incidence and severity of perioperative diffuse haemorrhages could significantly
      be reduced by routineous use of modern anesthesiological procedures, like
      controlled hypotension, total intravenous anesthesia (TIVA) and augmented
      ventilation techniques. Advances in interventional radiology reduced the risk of
      embolization of hypervascularized tumors and led to increasing application in
      recurrent epistaxis. A new generation of endoscopes combined with different laser
      techniques made the surgical treatment of hemorrhage more precise, increased the
      comfortability for the bleeding patient and were helpfull to decrease the length
      of stay and blood transfusion rates. CONCLUSION: Prevention and treatment of
      diffuse haemorrhages located within the craniocervical region can currently be
      optimized by an interdisciplinary dialog enrolling first of all the
      haemostaseologist and the anesthesiologist. Nowadays, close cooperation with the
      interventional radiologist is mandatory in the modern treatment of hypervascular
      lesions and vascular malformations. Moreover, it is necessary in emergency when
      otolaryngological measures faile to arrest bleedings from arterial site. Neither
      new techniques nor innovative strategies will be capable to compensate the
      experience and careful otolaryngologist.

PMID- 14634892
TI  - [Erroneous pathways in oncology (mistakes, errors and pathways in diagnostics and
      treatment of tumors of the upper airway and esophagus in clinic and outpatient
      locations)].

PMID- 14634893
TI  - [Fungi and polyps. Facts and myths].

PMID- 14634894
TI  - [Specialist standard under altered personal and economic circumstances].

PMID- 14634895
TI  - [Sonografic evaluation of oxygenation in head and neck cancer].
AB  - BACKGROUND: Tumor oxygenation is an important aspect of radiosensitivity. The
      authors describe a new method for a non-invasive assessment of tumor oxygenation
      in head and neck cancer. PATIENTS AND METHODS: A group of 20 patients with neck
      metastases of squamous cell cancer of the head and neck region was surveyed. At
      first a pO (2)-polarography was performed in the metastatic cervical nodes to
      investigate the tissue oxygenation. In a second step, the vascularisation of
      these nodes was visualised by color duplex sonography. In order to evaluate the
      extent of vascularisation in these nodes, the density of color pixels was
      quantified by a custom-made software program. The color pixel density and the pO
      (2) values were correlated and the statistic significance was calculated by
      Pearson's test. RESULTS: The mean vascularisation as evaluated by the means of
      color duplex sonography was 7.78 % [95 % CI 6.04 - 9.51]. The interindividual pO
      (2) values in the stroma of metastatic lymph nodes ranged between 9.0 and 27.4
      mmHg (16.6 [95 % CI 14.06 - 19.13]). The mean values of pO (2)-fractions < 2.5/<
      5.0/10 mm Hg were 32.25 %, 44.25 % and 53.29 % respectively. The median value of
      the pO (2)-fraction was 10.49 % [95 % CI 7.13 - 13.85]. The vascularisation as
      evaluated by color pixel density showed a statistically significant correlation
      with the pO (2)-fractions < 5.0 and < 10 mmHg (p < 0.045 and < 0.0001) and with
      the mean (p < 0.002) and median values of tissue pO (2) values (p < 0.0001) in
      polarography. CONCLUSION: The results in a limited number of patients suggest,
      that the proposed sonographic method allows a reliable non-invasive evaluation of
      tissue oxygenation in cervical metastases of squamous cell head and neck cancers.

PMID- 14634896
TI  - [The tolerability of nasal drugs with special regard to preservatives and physico
      chemical parameters].
AB  - BACKGROUND: Recent technical developments allow preservative-free nasal drug
      application in multi-dose systems. New pharmaceutical formulations for better
      tolerable nasal sprays are now possible and consequently reformulations
      introduced to the market. Therefore, a representative and systematic overview on
      comparable products is mandatory. METHODS: Marketed nasal products in the
      indication groups: decongestants, antiallergics, care and wound-healing, hormones
      and saline solutions were tested for their cytotoxic properties according to DIN
      EN 30 993 - 5, pH, and osmolality. RESULTS: In all indication groups
      reformulation to preservative-free application resulted in significant increase
      of cell growth and reduction of cytotoxicity. Physico-chemical galenic properties
      are of considerable importance too. With decongestants tolerability is dependant
      on the concentration of the active compound. CONCLUSIONS: Our data lead to the
      conclusion that preserved nasal sprays are obsolete, when preservative-free
      alternatives are available. Attention should be paid to galenic properties and
      dosage of the active.

PMID- 14634897
TI  - [Laryngeal papillomatosis - first recognition in Germany as an occupational
      disease in an operating room nurse].
AB  - BACKGROUND: The CO (2)-Laser is an established and well-proven tool in the
      excision and vaporisation of laryngeal papillomatosis. Actually there exists only
      one report of an iatrogenous infection with the Human Papillomavirs (HPV) in a
      gynecological laser surgeon. CASE REPORT: A 28-year-old gynecological operating
      room nurse, who assisted repeatedly in electrosurgical and lasersurgical
      excisions of anogenital condylomas, developed a recurrent and histologically
      proven laryngeal papillomatosis. The expert opinion of a virological institute
      confirmed a high probability of correlation between the occupational exposition
      and the laryngeal papillomatosis so that it was accepted as occupational disease.
      INFECTIVITY OF LASER PLUME: HPV-DNA has been repeatedly detected in laser-plume
      after excision of papillomas and condylomas. As of the present an exact proof
      that these particles are infectious has not been brought forward. CONCLUSION:
      When following the recommended protective measures the potential risk of
      infection is estimated as very low for surgeons and nurses. The risk of
      exposition seems to be higher in gynecological interventions than in ENT because
      of the much larger tissue masses and because laser plume escapes easier into the
      room air when applying an open approach.

PMID- 14634898
TI  - [Grisel's syndrome following ENT-surgery: report of two cases].
AB  - BACKGROUND: Non-traumatic atlanto-axial subluxation is a rare complication of
      upper neck inflammatory processes and head and neck surgery. It is called
      Grisel's syndrome named after P. Grisel, who first described this condition in
      1930. Persistent torticollis following head and neck surgery or upper respiratory
      tract infections should alert the surgeon to a beginning atlanto-axial
      subluxation. Due to lax ligaments it especially occurs in children and patients
      with Down's syndrome. PATIENTS: We present two cases of Grisel's syndrome in
      children following head and neck surgery with prolonged history, discussing
      pathogenesis, diagnostic measures and therapy. RESULTS AND CONCLUSIONS: Although
      there are several theories concerning the actual pathogenesis, it is generally
      agreed that an inflammatory process is the primary cause of Grisel's syndrome.
      Therefore, early antibiotic treatment is recommended. Further treatment depends
      on clinical findings and Fielding classification of the degree of the subluxation
      and includes muscle relaxations, soft collar or stiff neck, cervical traction or
      even arthrodesis of C1 and C2. If recognised early and appropriate treatment is
      applied, the prognosis is excellent. Severe cases can present with degenerative
      disorders of the cervical spine or even with neurological malfunction.

PMID- 14634899
TI  - [From the expert's office. Atlanto-axial subluxation with spastic torticollis
      after adenoid-ectomy resp. tonsillectomy in rose position - malpractice of the
      surgeon or the anaesthesiologist?].
AB  - INTRODUCTION: An arbitration board had to decide whether or not there had been a
      causal connection between an adenoidectomy or resp. a tonsillectomy and an
      atlanto-axial dislocation and if so whether this was to be considered a case of
      malpractice. CASE HISTORIES: In two young girls aged 6 and 11 a torticollis had
      developed 3 resp. 4 days after the operation. In both cases the proper diagnosis
      was made only after extensive diagnostic procedures including radiology,
      neurology, neurosurgery and orthopaedics. The findings are presented in detail.
      In both cases there was a rotary subluxation between cervical vertebrae C1 and C2
      due to a retropharyngeal inflammation. Normal function could only be achieved by
      surgical reposition and the application of a fixateur externe for quite a long
      period. DISCUSSION: A non-traumatic torticollis is a very rare complication of an
      adenoidectomy or tonsillectomy, two of the most common surgical interventions in
      oto-rhino-laryngology. It is known as Grisel's disease because Grisel in 1930 was
      the first to describe this sequel following nasopharyngitis and tonsillectomy. A
      detailed review of the literature and a discussion of the underlying pathology is
      presented. Predisposing factors might be additional local anaesthesia and electro
      haemostatis. CONCLUSIONS: : In both cases evidence for malpractice could not be
      found, neither concerning the intervention itself nor the handling in the
      postoperative period. The latency of several days between the operation and the
      manifestation of the torticollis is regarded as proof that intraoperatively there
      was no malpractice. In cases where the torticollis is present immediately after
      the intervention, as has been reported in the literature, a traumatic luxation
      during the operation or positioning of the patient may be taken into
      consideration. Because of the extreme rareness of the complication it does not
      seem compulsory to make it part of the preoperative informed consent.

PMID- 14634900
TI  - [Gene therapy in corneal diseases].
AB  - Gene therapy raised euphoric expectations in the past that have yet to be met and
      have even been lowered due to the absence of concrete clinical successes and the
      occurrence of some tragic incidents. In spite of the great future potential of
      gene therapy, numerous pilot studies in this field will probably be discontinued
      for a long time. However, despite these failures, diseases will continue to be
      the aim of gene transfer studies with experimental protocols using only temporary
      gene expression or those restricted to individual organs and thus requiring only
      a low dose of the vehicle (vector). The eye is exceptionally well suited as a
      potential target organ because of its good and selective accessibility, low
      volume and the resultant low number of gene ferries required as well as its
      special immunological status. The prognosis of corneal grafting can be improved
      and profit from the methods catalogue of gene transfer protocols. Moreover, the
      cornea can be used for ex vivo gene transfer before grafting. Ophthalmology could
      thus occupy a pioneer position in clinical gene transfer. A survey of the
      literature describes the current state of experimental improvement in corneal
      grafting, the effect on scarring, neovascularization, and herpetic corneal
      infection. The essential problem of gene therapy is the unsatisfactory gene
      transfer technique. Difficulties and current improvements are discussed.

PMID- 14634901
TI  - [Juvenile idiopathic arthritis and uveitis: screening and anti-inflammatory
      therapy].
AB  - This article provides an overview of the rheumatic diseases in childhood, their
      pathogenesis, epidemiology, diagnosis and clinical course. EULAR, ACR and the
      current ILAR-classification are compared. The antiinflammatory medical treatment
      is described. The characteristics of uveitis in the various forms of arthritis
      are reviewed. The prognostic factors for uveitis manifestation, the clinical
      course, complications, the prognostic factors for visual loss, and the diverse
      antiinflammatory medical regimens are evaluated. The suggestions of the "uveitis
      in childhood study group" concerning screening and treatment of uveitis in
      patients with juvenile idiopathic arthritis are provided, and a nation-wide
      documentation of these patients is described.

PMID- 14634902
TI  - [Correlation between confocal tomography of the optic nerve (HRT) and the
      perimetric frequency doubling technology].
AB  - PURPOSE AND METHODS: To correlate the five phases of optic nerve (ON) damage
      staging, as assessed by means of confocal tomography (HRT) with the five stages
      of visual field, assessed by conventional perimetry (standard automatic
      perimetry, SAP) and classified in five stages according to the "GLAUCOMA STAGING
      SYSTEM". The second step was to correlate the same optic nerve staging system
      with the results of the visual field tested with non-conventional perimetry using
      the frequency doubling technology (FDT) employing the Humphrey-Zeiss and Welch
      Allyn perimeter. The five stages of FDT visual field data evolution were
      classified according to the new "FDT STAGING SYSTEM". MATERIAL: 58 visual fields
      of 58 consecutive selected patients with either ocular hypertension or glaucoma
      with an age-range between 15 and 65 years. METHOD: Visual field examination was
      performed with conventional (Octopus G2 threshold test) and non-conventional
      perimetry (FDT N30 threshold test), and the ON was assessed with confocal
      tomography (Heidelberg Retina Tomograph). RESULTS: In 40 % of the visual fields
      tested normal with conventional perimetry, non-conventional perimetry (FDT)
      detected glaucomatous visual field defects corresponding topographically with the
      optic nerve damage revealed by HRT. CONCLUSIONS: New non-conventional perimetric
      techniques such as FDT enable the very early detection of visual field defects
      topographically correlated to optic nerve damage.

PMID- 14634903
TI  - [Prevalence of optic atrophy and associated ocular and systemic diseases in a
      department of paediatric ophthalmology].
AB  - BACKGROUND: Optic atrophy is one of the most common causes of severe visual
      impairment in children. So far an analysis of ocular and systemic findings
      comparing patients with and without optic atrophy has not performed. PATIENTS AND
      METHODS: Ocular and systemic findings of a total of 1042 patients (examination of
      all patients in May 1995 [N = 485] and May 2001 [N = 557]) of the department of
      paediatric ophthalmology in Homburg/Saar were retrospectively evaluated and
      diagnoses of patients with and without optic atrophy were compared. Optic atrophy
      was diagnosed ophthalmoscopically and in 1/3rd of the patients by VEP as well.
      RESULTS: 18 % of all patients (N = 188; 87.2 % [N = 164] were children) had optic
      atrophy. Nearly half of these children were prematurely born (46.7 %). 53.2 % of
      patients with optic atrophy (N = 88) showed nystagmus (without atrophy: 10.7 %),
      especially sensory defect nystagmus. Median of visual acuity level was 0.2 with
      optic atrophy and 0.8 without. Albinism and buphthalmia were common findings.
      69.5 % of all patients with optic atrophy suffered from systemic diseases
      (without atrophy: 25.2 %), especially mental retardation, neurologic findings and
      oculocutaneous albinism. In 10.4 % more than two systemic diagnoses could be
      found. 55.3 % of all the patients with optic atrophy were disabled, 31.9 %
      multiply disabled. CONCLUSIONS: Sequelae of prematurity, peripartal asphyxia and
      congenital brain damages are the main findings in patients with optic nerve
      atrophy. Such children are worst-case patients of any paediatric ophthalmology
      department with a high prevalence of severe visual impairment, mental retardation
      and multiple disability. Treatment in a specialised center is therefore necessary
      for an efficient therapy. In addition, the statistical survey shows that in
      children who survived the critical phases of prematurity secondary damages can
      lead to persistent impairment and to alterations of visual and general
      development.

PMID- 14634904
TI  - [Amiodarone treatment and visual prognosis].
AB  - BACKGROUND: Amiodarone is currently regarded as the most effective antiarrhythmic
      drug available for the treatment of tachyarrhythmias. Up to now, no
      recommendations exist concerning ophthalmological follow-up examinations at
      regular intervals of patients treated with amiodarone. METHODS AND PATIENTS: We
      examined six patients with a mean age of 71.7 years (five men, one woman) who
      were treated with amiodarone. RESULTS: One patient had no visual disturbances and
      a second patient had no permanent change of the optic nerve because treatment
      with amiodarone was discontinued in time. In one patient an abnormal blue colour
      vision was noticed. Swelling of the optic disc completely disappeared in five
      patients after discontinuing the drug. One patient revealed a posterior ischaemic
      optic neuropathy (PION). In two patients a unilateral change of the optic disc
      occurred. In three patients a severe irreversible lesion of the optic nerve was
      found at follow-up examination. CONCLUSIONS: An insidious visual loss can occur
      with amiodarone treatment. A swelling of the optic disc without visual
      deterioration can occur as the first sign of a defect of the optic nerve. An
      abnormal blue colour vision can also be detected. After discontinuation of
      amiodarone either a visual improvement or a permanent deterioration may result.
      We recommend that every patient being treated with amiodarone should be observed
      by opthalmoscopy and colour vision examination at regular intervals
      (approximately every 3 months). Treatment with amiodarone should be discontinued
      after exclusion of life-threatening situations by a cardiologist, as soon as the
      first changes of the optic disc occur.

PMID- 14634906
TI  - Gastrocnemius perforating artery flap including vascularized sural nerve.
AB  - A degree of communication was found between the superficial sural artery (the
      concomitant vessel of the sural nerve) and the muscle perforators from the
      gastrocnemius muscle, together with the cutaneous branches of the peroneal
      artery. A fasciocutaneous flap designed in the posterior calf region, including
      the vascularized sural nerve, was elevated based on the perforating artery of the
      gastrocnemius. This compound flap was used to reconstruct facial nerves and soft
      tissue defects created by resection of malignant tumors in three patients. The
      results were satisfactory, and facial animation returned in two patients, who
      were followed-up for more than 6 months. This compound flap offers several
      advantages, such as a long vascular pedicle with a sufficient diameter and a rich
      blood supply for the sural nerve and fasciocutaneous flap. This new technique
      should become another choice for vascularized sural nerve grafts, when the
      superficial sural artery or the cutaneous branches of the peroneal artery are not
      adequate for flap elevation or microsurgical anastomoses.

PMID- 14634905
TI  - [Spontaneous, bifocal rupture of the limbus in secondary angle closure glaucoma
      after open globe injury].
AB  - PURPOSE: To report on a case of bifocal rupture of the limbus that developed in a
      young male with secondary angle closure glaucoma 7 months after penetrating eye
      injury. CASE REPORT: A 20-year old male suffered from severe polytrauma due to a
      car accident. Examination revealed an open globe injury of the left eye due to
      corneal penetration by a foreign body (glass). After primary wound closure a pars
      plana vitrectomy with lens extraction and removal of the foreign body was
      performed. Five months later IOP increased markedly and could neither be
      controlled by antiglaucomatous medication nor by cyclophotocoagulation. Seven
      months after the injury a bifocal, closed rupture of the upper nasal and temporal
      corneoscleral limbus occurred. IOP of the eye was elevated despite the rupture.
      The limbal dehiscence was readapted and IOP increased again. A new limbal rupture
      occurred and a tectonic keratoplasty was performed. Because a marked thinning of
      the transplanted cornea occurred accompanied by strong evidence of advanced
      epithelial ingrowth the eye was enucleated. Histologic examination of the excised
      tissue and enucleated eye showed diffuse epithelial ingrowth. CONCLUSION: This is
      first reported case of delayed, spontaneous, bifocal rupture of the corneoscleral
      limbus after primary open globe injury. It may be speculated that severe
      contusion of the eye with structural damage of the corneoscleral limbus preceded
      the penetrating injury and that the later limbal rupture was caused by a marked
      elevated IOP due to epithelial ingrowth.

PMID- 14634907
TI  - Deep peroneal nerve transfer for established plantar sensory loss.
AB  - Patients with established or irreversible plantar sensory loss often have normal
      sensation on the dorsal aspect of the foot, due to an intact deep peroneal nerve.
      A new method of deep peroneal nerve transfer is proposed for repair of plantar
      sensory loss caused by extensive nerve gaps or high-level lesions of the
      posterior tibial nerve. Two cases in which this technique was used are described.
      The surgical technique is relatively easy, with a short operating time, rapid
      nerve regeneration after surgery, accurate sensory recovery, and minimal donor
      site morbidity with sensory loss only on the first web space of the foot.

PMID- 14634908
TI  - Microvascular free-tissue transfer for traumatic defects of the upper extremity:
      a 25-year experience.
AB  - Microvascular free-tissue transfer has been a major advance in the treatment of
      complex traumatic defects of the upper extremity. One hundred and fifty
      microvascular free-tissue transfers were performed in 133 patients with complex
      traumatic upper extremity defects at Bellevue Hospital Center from 1976 to 2000.
      The indication for microvascular free tissue transfers was exposure of vital
      structure (81 percent), bone defect (11 percent), and functional deficit (8
      percent). The parascapular region was the most common donor site used (26
      percent). Microvascular free-tissue transfer was performed either emergently at
      the time of injury (9.3 percent), during days 1 to 5 post injury (19.3 percent),
      during days 6 to 21 (19.3 percent), or after day 21 (52 percent). The overall
      flap failure rate was 9 percent. A decreased incidence of flap failure was
      observed in patients treated from 6 to 21 days post injury (3 percent p<0.05).
      The most common acute complication was infection at the recipient site, observed
      in 14 percent of patients overall. A decreased incidence of recipient-site
      infection was seen in patients who received free flaps at days 6 to 21 (3
      percent; p<0.05). In long-term follow-up, the incidences of osteomyelitis and
      nonunion were lowest in patients treated from 6 to 21 days post injury (0.0
      percent and 11 percent, respectively; p<0.05). During the last 10 years, the
      timing of reconstruction has been altered, and now preferentially microvascular
      free flaps are performed 6 to 21 days post injury. The treatment algorithm has
      been simplified and now only four different flaps are used in the majority of
      patients (70 percent). With this, the authors have witnessed a decrease in
      failure rates from 11 percent to 4 percent, a decrease in recipient-site
      infections from 16 percent to 10 percent and a decrease in osteomyelitis from 12
      percent to 4 percent. The preferred timing for microvascular free-tissue
      transfers to the upper extremity is concluded to be 6 to 21 days post injury.

PMID- 14634909
TI  - Is dextran infusion as an antithrombotic agent necessary in microvascular
      reconstruction of the upper aerodigestive tract?
AB  - Patent microvascular anastomoses are mandatory for a successful free tissue
      transfer. Dextran 40 is widely used by reconstructive microsurgeons in
      conjunction with free tissue transfer, to prevent flap loss. Unfortunately,
      dextran-induced adverse reactions, such as anaphylactoid reactions, adult
      respiratory distress syndrome, cardiac overload, hemorrhage, and renal damage,
      remain the major risks in routine use of dextran 40. The authors retrospectively
      analyzed the patency rates of 55 microvascular tissue transfers of a single
      microsurgeon after tumor ablation of malignancies of the upper aerodigestive
      tract between August, 1997 and March, 2001. The patency rates of free flap
      reconstructions were 96 percent for the dextran-infusion group and 100 percent
      for the dextran-free group. There was no statistically significant difference
      between the patency rates of these two groups. The results showed that the
      routine use of dextran as an antithrombotic agent is not necessary in
      microvascular reconstruction. The disadvantages of dextran infusion can be
      effectively prevented.

PMID- 14634910
TI  - Enhancement of rat sciatic nerve regeneration by fibronectin and laminin through
      a silicone chamber.
AB  - In this study, the authors examined the effects of fibronectin and laminin on
      sciatic nerve regeneration in rats. Sixty-eight Sprague-Dawley rats underwent
      bilateral sciatic nerve transections and silicone tubulizations, with a 10-mm gap
      between the proximal and distal nerve stumps. Thirty rats (n=30) received 10
      microg of fibronectin injection into the right sciatic nerve chamber, while
      saline was injected into the left nerve chamber, serving as the control. Another
      30 rats (n=30) were given 6 microg of laminin injection into the right nerve
      chambers and saline into the left chambers. At 1, 3, and 4 months
      postoperatively, electrophysiologic and histologic examinations, including nerve
      morphometry, were performed. Eight additional rats, receiving fibronectin (n=4)
      and laminin (n=4) injections, were used for horseradish peroxidase (HRP) tracing
      at 3 months postoperatively. Results from the study showed that fibronectin- and
      laminin-treated groups had significantly higher motor nerve conduction velocity
      and evoked muscle action potential amplitude of the anterior tibial muscle than
      the control group (p<0.01). Nerve diameter and the number of myelinated axons
      from the groups receiving fibronectin and laminin applications were greater than
      the controls (p<0.01). Also, a greater number of HRP-labeled motor neurons were
      found in the ventral horns and dorsal root ganglia of the fibronectin- and
      laminin-treatment groups compared to the controls. The authors conclude that
      local applications of fibronectin and laminin into the nerve chambers can
      significantly improve axonal regeneration and maturation of injured rat sciatic
      nerves.

PMID- 14634911
TI  - Effect of the delay phenomenon on survival of rat island skin flaps with total
      venous occlusion.
AB  - Necrosis is an inevitable result in flaps with total venous occlusion even if
      arterial flow is sufficient. The purpose of this study was to investigate the
      effect of surgical delay on rat island skin flaps with total venous occlusion,
      using 20 Swiss albino rats. Two epigastric island flaps were elevated in each
      rat. Flaps of experimental and control groups were elevated in the same animal.
      In the experimental group (n=20), flap boundaries were incised down to the fascia
      and the incisions were sutured as a delay procedure at the first stage. After 7
      days, the 3 x 6-cm epigastric island flap was elevated, the inferior epigastric
      vein was ligated, and was cut under X60 magnification. Then, all flaps were
      sutured back to their original beds. In the control group (n=20), the same
      surgical procedure as in the experimental group was repeated without a delay
      procedure. Viability was assessed at postoperative days 1, 3, and 7. At the end
      of day 7, all flaps in the control group were totally necrosed; however flaps in
      the experimental group survived partially. The surviving area ranged between 24
      and 74 percent (mean: 60 +/- 15 percent). The differences between the two groups
      were found to be statistically significant, using Student's t-test ( p<0.005).
      Surgical delay could not completely save a flap with totally interrupted venous
      return. Nevertheless, a 60 +/- 15 percent portion of these flaps could survive
      with the help of a simple delay procedure.

PMID- 14634912
TI  - Experimental fascial flap model in the dog: free flap of the dorsal thoracic
      fascia.
AB  - For years, various types of fascial flaps have been used in clinical practice;
      however, there are many unanswered questions regarding their basic physiology,
      anatomy and histopathologic changes occurring after transfer. Simple and reliable
      flap models are needed to investigate these questions, but very few of these flap
      models have been described in experimental animals to date. The purpose of this
      study was to describe a new reliable fascia flap model in the dog-the dorsal
      thoracic fascia flap. This fascia is defined as the anatomic layer that contains
      the blood supply to the scapular and parascapular fasciocutaneous flaps. Fourteen
      adult dogs were used in this experiment. The vascular anatomy of the dorsal
      thoracic fascia was studied by anatomic dissection and microangiography. Anatomic
      dissection revealed that the main axial vessel supplying the dorsal thoracic
      fascia was the superficial branch of the thoracodorsal vessel. Based on the
      vascular pedicle, fascia flaps generally measuring 15 x 24 cm were created. At
      gross observation, all of these large flaps based solely on the vascular pedicle
      were observed to be well-perfused. Microangiographic examination revealed the
      intense vascularity of the superficial branches of the thoracodorsal vessels in
      the whole area of all flaps. It was concluded that this is a simple and reliable
      fascial flap model which can be prepared as a free or pedicled flap. It has a
      consistent, long vascular pedicle with large vessel diameters supporting a large
      fascial flap.

PMID- 14634913
TI  - Tensile strength of healing peripheral nerves.
AB  - Although the time required for a nerve to gain sufficient strength to withstand
      normal physiologic forces of joint motion is unknown, typically nerve repairs are
      protected up to 3 weeks postoperatively. The authors investigated the mechanical
      strength of a nerve repair as a function of time. Fifty adult Sprague-Dawley rats
      underwent sciatic nerve division and repair, and were sacrificed in groups of 10
      at 0, 1, 2, 4, and 8 weeks. Repaired nerves were then mechanically loaded at 5
      mm/min to failure. Gapping across the repair site was captured on high-resolution
      video. The contralateral sciatic nerve served as a control. A significant
      increase in tensile strength was gained between 0 and 1 week and between 2 and 4
      weeks. Healing nerves achieved 63 percent of the strength of the control by 8
      weeks. Controls showed no gain in strength over the testing period. Gapping
      occurred at lower forces at all time increments. From 0 to 1 week, a significant
      increase in load necessary to produce gapping was found, which did not increase
      significantly again until 8 weeks. These results may have implications for
      postoperative rehabilitation protocols in patients with nerve injuries.

PMID- 14634915
TI  - [Factors related to the short term remission of tics in children with Tourette
      syndrome].
AB  - INTRODUCTION: Tourette syndrome shows a fluctuating evolution, often masked by
      its comorbidity. OBJECTIVE: To study the clinical factors predicting the initial
      remission of tics in children with Tourette syndrome. Patients and methods. All
      patients attended during the last 5 years at a Child Neurology hospital based out
      patient clinic, with the diagnosis of Tourette syndrome according to DSM IV
      criteria, were selected. OUTCOME MEASURE: total remission of tics during at least
      3 months, evaluated during the patient s second visit to our clinic. Demographic,
      clinic and therapeutic variables were studied. Statistical analysis was based on
      the Student t test or non parametric tests, as necessary. RESULTS: 53 patients,
      44 males and 9 females. Age at starting tics: 6.9 2.2 years, time of evolution: 2
      years (range: 1 9.4). Comorbidity in 51%: 34% with attention deficit
      hyperactivity disorder (ADHD), 17% with obsessive compulsive disorder (OCD) and
      school underachievement: 26%. Familial antecedents of tics, OCD, or ADHD: 49%.
      Tics remission at second visit to our clinic: 41.5%. Patients without remission
      were those with an earlier onset of tics (p=0.085), longer time of evolution (p<
      0.05), or school underachievement (p= 0.024). Remission was not statistically
      associated with treatment. OCD and ADHD were associated with school failure but
      were not related to the tics evolution. CONCLUSION: The short term (at second
      visit), temporal (minimum 3 months) total remission of Tourette syndrome was not
      related to treatment but to previous duration of the syndrome and to factors
      (other than OCD and ADHD) that lead to school failure.

PMID- 14634916
TI  - [Electroencephalographic alterations in children with attention deficit
      hyperactivity disorder].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a syndrome that
      affects between 3 5% of the population of school aged children, and may be
      accompanied by learning, language, behavioural or motor disorders. Although
      various electroencephalographic alterations have been described in these
      patients, their pathological significance has not been determined. There have
      also been reports of children with neuropsychological and language disorders
      having epileptiform anomalies in the EEG recording. PATIENTS AND METHODS: We
      conducted a study of 15 children, with no history of seizures, who had been
      referred to Child Neurology for treatment and who satisfied the criteria for ADHD
      according to the DSM IV and the ADHRS (attention deficit/hyperactivity rating
      scale). RESULTS: The EEG recording in the waking state showed significant
      anomalies in two of our patients (acute spike and wave paroxysmal activity in the
      left temporoparietal region and spike wave discharges during hyperventilation).
      The polysomnographic study revealed specific alterations in four children. There
      was a continuous spike wave trace during slow sleep (CSWS) in one case,
      paroxysmal activity (slow acute waves, spikes) in the temporoparietal region with
      secondary generalization or transmission (two cases), and frequent generalized
      paroxysmal discharges of slow acute waves in all phases of sleep (one case).
      CONCLUSIONS: The neurophysiological disorders observed in some of our patients
      could make it necessary to consider performing a night time polysomnographic
      study in certain cases of ADHD.

PMID- 14634917
TI  - [Clinical significance of correcting the serum level of phenytoin according to
      the albuminaemia in hospitalized patients and outpatients].
AB  - INTRODUCTION: It has recently been reported that in developing countries, which
      have a high prevalence rate of hypoalbuminaemia, the total concentration of
      phenytoin in serum would often provide incorrect clinical information. PATIENTS
      AND METHODS: The serum levels of phenytoin and albumin were determined in 400
      adult patients of both sexes (231 hospitalized and 169 outpatients) attended in
      our hospital, and the concentrations of the drug were corrected using the Sheiner
      Tozer equation (STE). RESULTS: A clinically significant difference between the
      corrected and experimental concentrations of phenytoin (< 1.2 mg/L) was found in
      74.4% of the hospitalized patients and in 21.3% of the outpatients. CONCLUSIONS:
      According to these findings and given the fact that determining the concentration
      of free phenytoin (i.e. not linked to albumin) is not routinely carried out, we
      recommend the systematic correction of phenytoin levels in our community in order
      to better adjust dosages. The possible limitations of the use of STE for
      standardizing phenytoin concentrations are also discussed.

PMID- 14634918
TI  - [A comparative study of the treatment of high grade gliomas].
AB  - INTRODUCTION: The influence of surgery, radiotherapy and/or chemotherapy on the
      outcome on the results in patients with malignant gliomas is controversial.
      PATIENTS AND METHODS: We studied 44 patients (26, women; 18 men; age 38 72 years)
      diagnosed with grades III and IV astrocytoma who had been operated and then
      received adjuvant radiotherapy and either BCNU or temozolamyde chemotherapy.
      Survival time and adverse effects of the chemotherapy were analysed. CONCLUSION:
      Aggressive surgery associated with radiotherapy and temozolamyde chemotherapy
      prolonged survival in our patients with malignant astrocytomas.

PMID- 14634919
TI  - [Plasmapheresis: its use in multiple sclerosis and other demyelinating processes
      of the central nervous system. An observation study].
AB  - INTRODUCTION: We present a retrospective observation study aimed at analyzing the
      value of plasmapheresis in the management of patients with multiple sclerosis
      (MS) and other acute demyelinating processes affecting the central nervous system
      (CNS) who show severe exacerbations that do not respond well to conventional
      therapy with corticoids. PATIENTS AND METHODS: A total of 11 patients were
      included in the study: nine with MS, one disseminated acute encephalomyelitis and
      one case of transverse myelitis. All of them presented an acute or subacute
      neurological deficit, which prevented them from carrying out their day to day
      activities, with or without repercussions on the EDSS, and with the risk of
      suffering a severe residual disability after not responding to intravenous
      methylprednisolone pulses. Each patient was submitted to three exchanges per
      week, for 2 weeks, with association of orally administered prednisone and they
      were then evaluated after the last session and at one, six and twelve months.
      RESULTS: Following plasmapheresis all the patients experienced a significant drop
      in disability and seven of them (77.7% of the total number with MS) even improved
      during the first month with respect to their basal situation ( an extension of
      the Lazarus effect ). After a year s follow up, 100% of the patients still
      maintained the basal situation that was recovered from before exacerbation, and
      only two relapses were recorded. The patients with MS presented a transient
      exacerbation after the second exchange. New therapy with immunosuppressants,
      immunomodulators or both was associated in eight cases. CONCLUSIONS: We consider
      plasmapheresis to be a safe, effective therapeutic procedure in the management of
      patients with MS and other demyelinating processes affecting the CNS. Its use
      should be considered as first choice in severe relapses and in swiftly
      progressing forms that do not respond to intravenous methylprednisolone.

PMID- 14634920
TI  - [Do age and service influence on diagnostic quality of ischemic stroke?].
AB  - BACKGROUND: The ischemic stroke represents a very important cause of death in the
      hospitals. The clinic changes of this disease and the frequent morphological
      evidence in necropses motived the study of the clinicopathological concordance
      taking as reference two institutions of the secondary attention. The two medical
      centers were our study was conducted were: Dr. Gustavo Alderegu a Lima Hospital
      in Cienfuegos and Camilo Cienfuegos in Sancti Spiritus. These two Cuban hospital
      have showed necropses indicators higher than 80%. OBJECTIVES: To determine the
      clinicopathological correlation of the ischemic stroke as evidence of the quality
      of the diagnoses. The influence of the age of the patient and kind of care
      received by the patient. PATIENTS AND METHODS: A retrospective, descriptive, and
      correlational study where 1556 death with necropsy were evaluated. As main
      variables were studied the age and services where demise took place, as well as,
      the following indicators: observed concordance, kappa index, sensitivity,
      specificity, positive and negative predictive values, positive and negative
      similarity reasons. RESULTS: At ischemic cerebrovascular lesions the concordance
      was significant with kappa values which were not higher than 0.66 in both
      facilities; nevertheless, sensitivity and positive predictive value were higher
      in Sancti Spiritus (75.5% and 63.5%, respectively). Overall, being aged was not a
      motive for diagnostic discordance on cerebrovascular damages, significantly the
      Sancti Spiritus values in the ages group were substantial: kappa (0.70),
      sensitivity (80.4%), and positive predictive value (19.0). Among death from 15
      thought 60 years old from Sancti Spiritus province the results of measurements of
      diagnostic quality were reduced comparative with Cienfuegos and overall for this
      age group: kappa (0.37), sensitivity (42.8%), positive predictive value (37.5%).
      Analysis of each services evidence reductions of sensibility up to (59.1%) at
      clinic services of Cienfuegos with respect to (73.6%) progressive care for
      ischemic cerebrovascular lesions, besides a positive predictive value of (49.4%)
      in progressive care, lower than the results obtained for Sancti Spiritus.
      CONCLUSIONS: The clinicopathological concordance and the rest of the quality
      indicators were higher in Camilo Cienfuegos Hospital in Sancti Spiritus. The age
      below 60 years old favoreced the diagnostic discordance in the above mentioned
      center. Nevertheless, patients with age over 60 years old didn t show important
      changes in the concordance. The quality indicators were higher in unit f
      intensive care respect to the clinical services. The quality in the results in
      the Sancti Spiritus Hospital are determined by the existence of a stroke unit

PMID- 14634921
TI  - [Transient ischemic attacks as the only manifestation of a dural arteriovenous
      fistula].
AB  - INTRODUCTION: Transient ischemic attacks (TIA), as the only clinical
      manifestation of a dural arteriovenous malformation, are very seldom seen in
      clinical practice. CASE REPORT: We describe the case of a 68 year old male with
      recurring bouts of right hemiparesis, due to haemodynamic alterations stemming
      from a dural arteriovenous malformation located in the right middle fossa, with
      cortical venous drainage towards the superior longitudinal sinus, which hampers
      the drainage of the left parietal cortical veins. Computerized tomography and
      magnetic resonance scans performed on admission to hospital revealed blood in the
      left parietal sulcus, with no parenchymatous lesions. This dural arteriovenous
      fistula was initially treated by the endovascular administration of polyvinyl
      alcohol in 150 250 mm particles, but after 11 days the patient again presented
      symptoms of right hemiparesis which became increasingly frequent and intense.
      This led to the search for a definitive treatment for the dural arteriovenous
      fistula with cyanoacrylates. No similar symptoms have been observed in the five
      years follow up carried out after the embolization. CONCLUSIONS: In cases of
      dural arteriovenous fistulas the arterialized cortical vein can impede the
      drainage of other veins towards the common venous sinus. On very rare occasions
      this can lead to the appearance of symptoms of transient ischemic attacks in
      territories that are a long way from the location of the abovementioned
      arteriovenous malformation.

PMID- 14634922
TI  - [Severe polymyositis with simvastatin use].
AB  - INTRODUCTION: Myotoxicity is the most common adverse reaction of statins, being
      its frequency less than 0.5%. Mild myopathy reversible after statin withdrawal is
      the most common event. We present a case of severe polymyositis which was likely
      to be induced by simvastatin. CASE REPORT: 75 years old man with
      hypercholesterolemia treated with simvastatin 20 mg/day for 6 months started
      previous 2 months with proximal limb weakness, dysphagia and myalgias during
      exercise that did not release after simvastatin withdrawal. Laboratory findings
      showed increased creatinin kinase (6,010 UI/L), raised aldolase (51 UI/L) and
      lactic acid dehydrogenase (1,406 UI/L). Muscular biopsy showed abundant
      inflammatory cell infiltration in perivascular areas, muscle fibre necrosis with
      miofagocitosis and considerable variation in fibre size, some of them reaching
      210 mm. Treatment with cortico esteroids was started and 4 months later clinical
      remission and nomalization of creatinin kinase was observed. DISCUSSION:
      Mechanisms of statins induced myotoxicity are not well known. Studies in rats
      suggest a muscle membrane defect (increased membrane fluidity) and abundant signs
      of damage (fiber necrosis, hipercontraction) but no cellular infiltrates were
      seen, pointing to a non inflammatory myopathy which was dose dependent. In our
      case, and Giordano s et al, the remission of the disease with cortico esteroid
      therapy and the finding of abundant inflammatory cell infiltration suggest the
      implication of immunological mechanism and not only a muscle membrane defect.

PMID- 14634923
TI  - [Superficial haemosiderosis of the central nervous system, neuro otological
      manifestations and images from a magnetic resonance brain scan: a case report].
AB  - INTRODUCTION: Superficial haemosiderosis of the central nervous system (SHCNS) is
      an infrequent clinical entity; it is produced by the formation of clinically
      silent haemosiderin deposits in the leptomeninges, the subpial tissue, the
      cranial nerves and spinal cord, secondary to chronic bleeding in the subarachnoid
      space. Aetiology is idiopathic in half the cases or secondary to a vascular
      malformation or other structural abnormalities. At least 100 cases have been
      reported in the literature, most of which were diagnosed post mortem. In these
      descriptions there is a predominance of cerebellar ataxia, progressive
      hypoacusis, nystagmus, recurring headaches, pyramidal signs, an absence of
      caloric responses and xanthochromic cerebrospinal fluid. Magnetic resonance (MR)
      brain scanning in T2 revealed hypointensity in the brain stem, the cerebellum and
      the Sylvian fissure, with atrophy of the cerebellum and the brain stem. CASE
      REPORT: A 64 year old male with bilateral tinnitus and progressive neurosensory
      hipoacusis, who visited because of loss of balance, urinary incontinence and
      oscillopsia. The patient s personal history included an episode of unbearable
      headache at the age of 53. The neurological and neuro otological examination was
      pathological and the MR brain scan confirmed the diagnosis of SHCNS. CONCLUSIONS:
      We wish to highlight how extremely rare this entity is, and especially so when
      there is a predominance of progressive neuro otological manifestations; we also
      want to emphasize the importance of carrying out specific imaging studies to
      enable a diagnosis to be made while the patient is still alive.

PMID- 14634924
TI  - [Parry Romberg syndrome associated with refractory epilepsy, atrophy of the dura
      mater and cystic leukoencephalopathy].
AB  - CASE REPORT: We report the clinical and radiologic observation in a man patient
      of 20 years old. He developed gravity left progressive facial hemiatrophy. In
      associated form, he presented numerous visual sensories and complex partials
      seizures. The single and combined treatment with several antiepileptic drugs was
      ineffective for the control of the epilepsy. The magnetic resonance investigation
      of the cranium facial structures showed the gravity and intensivity of the
      dysmorphia. The same procedure showed the strong of the duramadre atrophy in the
      convexity of the brain, as well as, the existence of the cystic formation in the
      white matter of the left temporo occipital region at the face affected.
      CONCLUSION: We considered, that this is the first report documented fully, about
      the Parry Romberg syndrome with refractory epilepsy, duramadre atrophy and cystic
      leukoencephalopaty, published in Peru.

PMID- 14634925
TI  - [Non-convulsive epileptic status associated with Lafora disease: two case
      reports].
AB  - INTRODUCTION: Lafora s disease is a type of progressive myoclonic epilepsy with
      poor prognosis, is characterized by myoclonic crisis, tonic clonic seizures,
      absence or partial complex seizures and other neurological manifestations with a
      progressive course and a poor response to the treatment. It has not been
      considered as a cause of epileptic status. CASE REPORTS: Two women without
      important past medical history with normal psychomotor development before their
      suffering, with manifestations of 2 years of evolution the first one and 8 years
      on the second case characterized by myoclonic generalized, partial complex
      seizures and progressive deterioration of the mental functions that joined to our
      institution in a non convulsive epileptic status and they featured with a
      different evolution. The first patient with favorable control of the event with a
      single medication and functionality recover later, the second one with torpid
      evolution complicated with an epileptic status convulsive widespread condition
      and a prolonged permanency in the unit of intensive therapy. In both patients the
      diagnosis of Lafora s disease was established based in the findings of the skin
      axilar biopsy. DISCUSSION AND CONCLUSION: We believe that Lafora s disease must
      be suspected as a probable cause of non convulsive epileptic status in patients
      with myoclonic epilepsy associated with other neurological manifestations and a
      refractary response to the medical treatment. The evolution and clinical response
      will depend on the evolutionary stage of the disease.

PMID- 14634926
TI  - [Oxcarbazepine induced interstitial nephritis in a patient with drug
      hypersensitivity syndrome].
AB  - INTRODUCTION: Antiepileptic drugs (AED) have long been known to have a series of
      side effects and descriptions of drug hypersensitivity syndrome (DHS) have often
      linked it with these agents. This is more especially so in the case of those with
      an aromatic ring, but also in those that lack such a structure. CASE REPORT: We
      describe a case of DHS related to the administration of oxcarbazepine (OXC), a
      ketoanalogue of carbamazepine (CBZ) that has recently appeared on the market in
      our country, which coursed with interstitial nephritis as the most important
      clinical manifestation. Our patient developed fever, vomiting, itchy exanthema,
      kidney failure and biochemical anomalies in the liver after two weeks treatment
      with this drug. After stopping administration of this anticonvulsant and giving
      the patient corticoids, the clinical manifestations disappeared and the
      analytical anomalies began to improve. CONCLUSIONS: OXC can give rise to DHS in
      the same way as other AED with an aromatic ring structure (phenytoin,
      phenobarbital, primidone, CBZ and probably also lamotrigine) or without an
      aromatic ring structure (valproic). Interstitial nephritis may be the most
      significant and serious clinical manifestation of DHS produced by OXC. According
      to the review of the literature we carried out, to date no descriptions of this
      association of nephritis caused by OXC in the context of DHS have been reported.

PMID- 14634927
TI  - [Review of the literature on the value of magnetoencephalography in epilepsy].
AB  - INTRODUCTION: Magnetoencephalography (MEG) it is a non invasive technique of
      recording the brain activity, based on the detection of magnetic fields. Aim. It
      is sought to determine the relative contribution of MEG to the handling of
      patients with epilepsy concerning to other diagnostic technics like scalp EEG, v
      EEG (v EEG), electrocorticography (EcoG), magnetic resonance (MR and MRf),
      positron emission tomography (PET) and single photon emission tomography (SPECT).
      METHOD: It has been carried out it a critical revision of the literature, using
      the approaches of the evidence based medicine (EBM). In the databases MEDLINE and
      HEALTH START, among the years 1996 and 2001, it were found 1169 references. After
      the one sieved, 36 were selected, of those that chose 22 definitively for their
      analysis: 3 articles were classified as of Technical Effectiveness and 19 as
      Effectiveness in Diagnostic Accuracy. For the methodological quality, 2 were
      classified as of group B, 16 in C and 4 in D. Eighteen articles make reference to
      MEG and pharmaco resistant epilepsy, while other 4 they make reference to MEG and
      pharmaco sensitive epilepsy. Sensibility is highly variable, being bigger in
      extratemporal epilepsy (44 92.9%), then in temporal (33.3 80%) and smaller in
      mesial temporal (42.3 53%). Specificity is bigger for patient with anatomical
      lesions. CONCLUSION: 1. Localization of interictal activity is better in
      neocortical lateral regions, diminishing in mesial ones, 2. The methodological
      deficiencies of the articles prevent to carry out a meta analysis of the data.

PMID- 14634928
TI  - [Cognition and neural networks, a new perspective based on functional
      neuroimaging].
AB  - AIM: We went through a critical review of the current status of neuroimaging
      studies of cognition. Thus, we argue why the use of a neuronal network
      perspective could led us to a better understanding of cognition than a
      localizationism perspective. METHOD: The question about how cognitive functions
      are organized in the brain, comes from the very early lesions studies.
      Electrocortical stimulation and the intracorotid amytal procedure collaborate
      together with lesions studies to increase the knowledge about the organization of
      cognitive functions in the brain. Functional neuroimaging could help to this
      issue answering the following questions: where, when and how the activity is
      produced in the brain. Many of the functional neuroimaging studies have addressed
      the question of where the activity is located, but very few has been concentrated
      into describe the spatio temporal profiles of brain activity, and then how the
      neural networks which support cognition are organized. Taking into account just
      one of this perspectives (where or when) we could achieve a reductionism view of
      the problem. CONCLUSIONS: Executive function, memory or language are more
      distributed than located in just one area, even the different subprocesses that
      are included in each of this functions are supported by a network rather than a
      particular area. We analyze the current available functional neuroimaging
      techniques under this view and its possibilities to describe the neural networks
      which support cognition.

PMID- 14634929
TI  - [Modes of treatment for arteriovenous malformations of the brain].
AB  - INTRODUCTION AND DEVELOPMENT: Over the years new kinds of therapy have been
      incorporated into the treatment of arteriovenous malformations (AVM). Current
      treatment of AVM of the brain employs three well established options:
      radiosurgery, endovascular therapy (embolisation) and microsurgical resection.
      Radiosurgery is the simplest and least invasive, but 2 3 years are required to
      achieve total obliteration, and throughout this time there is the risk of
      bleeding; its use is limited to small AVM. Embolisation today plays a fundamental
      role more as an adjunct than when it is associated, although the other modes
      improve their cure interval by 25%. Microsurgery has the advantage of being the
      only mode of therapy that offers a degree of immediate angiographic obliteration
      of almost 100% and is still the most widely employed, despite its morbidity rate
      also being the highest. We establish an AVM management algorithm, in which,
      according to the size and localisation, we suggest that these therapeutic options
      should be used alone or in combination. CONCLUSIONS: The management of these
      lesions requires a combined effort of all the factors that can be of any help in
      the solution, and these modes are more complementary than competitive in
      situations in which they are all valid therapeutic options.

PMID- 14634930
TI  - [Polycystic ovary syndrome and valproic acid].
AB  - INTRODUCTION: The reproductive functions of epileptic females often display
      alterations. This dysfunction can be due to psychological, physiological or
      pharmacological factors. These women have been described as having, for example,
      a higher incidence of anovulatory cycles, infertility, alterations affecting the
      hypothalamic or pituitary hormones and the peripheral sex hormones. The greater
      incidence of polycystic ovary syndrome is subject to debate, since the prevalence
      varies according to the eligibility criteria used for the syndrome. DEVELOPMENT:
      The series that show a positive relation between polycystic ovary syndrome and
      epilepsy tend to understand it to be a side effect of antiepileptic medication,
      especially valproic acid. Two theories are considered: it has a direct action on
      the sex hormones or hyperinsulinism that is secondary to weight gain. As
      neurologists, in our daily practice we must show concern for the conceive.
      Moreover, we must determine the baseline reproductive hormonal functioning of the
      epileptic female before beginning antiepileptic therapy, provide laboratory
      backed evidence of any sexual function disorder and refer them to the
      reproductive and sexual health of epileptic women. To do so, we need a patient
      record that is aimed at detecting possible problems, with special attention being
      given to the warning signs , such as changes in weight, variations of the
      menstrual cycles or mid cycle bleeding, the appearance of androgynous obesity,
      signs of virilisation, miscarriages or difficulties to endocrinologist or
      gynaecologist. CONCLUSIONS: Knowledge about both pathologies will enable us to
      modify antiepileptic therapy if the relation it has with them is confirmed, since
      this side effect could be reversible.

PMID- 14634931
TI  - [The vestibular organ throughout history].
AB  - AIMS AND DEVELOPMENT: Our aim is to attempt to create a chronologically ordered
      and coherent corpus of the apparently scarce information that exists about the
      history of the vestibular organ, a component of the inner ear situated on both
      sides of the head in the petrous temporal bone. Its job, at least in humans, is
      to transmit sensory information about movements of the head to components of the
      central nervous system. Some of its more common disorders lead to syndromes that
      implicitly entail balance disorders, such as the case of the syndrome described
      by Prosper Meni re in the 19th century. Without ruling out the possible ancestral
      knowledge of the vertiginous processes associated with the inner ear, our
      objective is to review some of the aspects that anatomists, physiologists and
      prominent physicists have been involved in throughout history, i.e. elements that
      appeared between the 18th and mid 20th century and which have led to a fuller
      understanding of the morphological and functional aspects of the fundamental
      apparatus involved in the detection of gravity and inertia, shared by
      vertebrates: the vestibular organ.

PMID- 14634933
TI  - [Peripheral polyneuropathy, hypoacusis and optical neuropathy with probable toxic
      and deficiency related origins].

PMID- 14634934
TI  - [Depressive disorder and craniopharyngioma].

PMID- 14634935
TI  - Neurolytic celiac plexus block for benign pain: still a question?

PMID- 14634936
TI  - The scientific method, evidence-based medicine, and rational use of
      interventional pain treatments.

PMID- 14634937
TI  - Pain prevention strategies that work.

PMID- 14634938
TI  - A comparison of a triple-injection axillary brachial plexus block with the
      humeral approach.
AB  - BACKGROUND AND OBJECTIVES: This prospective, randomized, and single-blind study
      compared effectiveness, performance, onset, and total anesthetic time and
      complications of the multiple axillary block (median, radial, and
      musculocutaneous nerves) with the humeral approach. METHODS: One hundred patients
      were randomly assigned to 2 groups. In group A (axillary) median, radial, and
      musculocutaneus nerves were located by a nerve stimulator and injections were
      made. In group H (humeral) all 4 terminal nerves of the brachial plexus were
      located and injections were made. A total of 40 mL mepivacaine of 1% was used.
      RESULTS: Complete sensory block of all 6 peripheral nerves occurred in 94% and
      79% of patients in groups A and H, respectively (P < .05). The time to perform
      the block was shorter in group A (8 +/- 4 minutes v 11 +/- 4 minutes; P < .001);
      onset time was shorter in group A (16 +/- 8 minutes v 21 +/- 9 minutes; P < .05);
      total anesthetic time was shorter in group A (24 +/- 8 minutes v 33 +/- 10
      minutes; P < .0001). Complete motor block was greater in group A (88% v 66%; P <
      .05). More vascular punctures occurred in group A (22% v 8%, P < .05).
      CONCLUSION: The triple-injection axillary block was more effective than the
      humeral approach as it was associated with more cases of sensory and complete
      motor block and gave shorter performance and onset times.

PMID- 14634939
TI  - Influence of lumbar flexion on the position of the intercrestal line.
AB  - BACKGROUND AND OBJECTIVES: This study was performed to ascertain whether the
      position of the intercrestal line changes as a result of flexion of the lumbar
      spine. METHODS: Previously taken lumbar spine x-rays of 103 patients in the
      neutral and full-flexed positions were reviewed. In the lateral flexion images to
      compensate for the sagittal rotation of the pelvis during lumbar flexion and for
      the possible difference in the level between the two sides of the ilium when
      taking the lateral images, the intercrestal line was drawn as follows: a
      potential line, crossing the midpoint of the highest points of both iliums,
      should be perpendicular to the tangential line at the point of intersection of
      the potential line with the skin. The position of the intercrestal line in
      relation to the spinous process was determined on an imaginary line moved 1 cm
      toward the vertebral body from the tangential line on the 2 successive spinous
      processes, and the interspinous distance of L3-4 was measured on this imaginary
      line. RESULTS: With full-flexion of the lumbar spine, the position of the
      intercrestal line in relation to the spinous process [median (25th to 75th
      percentiles)] changed slightly from L4 (L4-L4-5) into L4-5 (L4-L4-5) (P <.001),
      but it remained at the same level in 58.3% of the patients (60/103). In no case
      was a change of more than 1 level observed. The interspinous width (mean +/- SD)
      of L3-4 increased from 6.5 +/- 2.4 mm to 13.2 +/- 4.4 mm (P <.001). CONCLUSION:
      When compared with the neutral position, the position of the intercrestal line
      usually does not change with full flexion of the lumbar spine, and even in cases
      in which change occurs, it does not move beyond the next level.

PMID- 14634940
TI  - Subarachnoid catheter placement after wet tap for analgesia in labor: influence
      on the risk of headache in obstetric patients.
AB  - BACKGROUND AND OBJECTIVES: The incidence of postdural puncture headache (PDPH)
      after epidural wet tap for obstetric patients may be as high as 75%. We have
      studied how subsequent placement of a subarachnoid catheter immediately after
      confirmation of a wet tap, and leaving the catheter in place for 24 hours affects
      the incidence of PDPH. METHODS: Over a 5-year interval, 115 consecutive patients
      who had unintentional dural puncture were divided into 3 groups by consecutive
      assignment. Group A had an epidural catheter placed at another interspace. Group
      B had a subarachnoid catheter placed for labor analgesia that was removed
      immediately after delivery. Group C had a subarachnoid catheter that was left in
      place for 24 hours after delivery. Data were collected retrospectively. The
      incidence of PDPH and blood patch was compared between groups. RESULTS: The
      overall incidence of PDPH was 46.9% and need for blood patch 36.5%, significantly
      less in both subarachnoid catheter groups, 31% in B and 3% in group C, compared
      with group A (PDPH 81%) (P <.001). CONCLUSION: Subarachnoid catheter placement
      after wet tap in obstetric patients reduces the PDPH rate and does so to a
      greater extent if left in place for 24 hours after delivery.

PMID- 14634941
TI  - Lateral approach to the sciatic nerve in the popliteal fossa: a comparison
      between 1.5% mepivacaine and 0.75% ropivacaine.
AB  - BACKGROUND AND OBJECTIVES: Ropivacaine and mepivacaine are commonly used local
      anesthetics for peripheral nerve blockade. The purpose of the present study was
      to compare onset time, quality of anesthesia, and duration of analgesia with
      ropivacaine 0.75% and mepivacaine 1.5% for lateral popliteal nerve block.
      METHODS: Fifty American Society of Anesthesiologists (ASA) physical status I or
      II patients scheduled for foot and ankle surgery with calf tourniquet under
      lateral popliteal sciatic nerve block were randomly assigned to receive 30 mL of
      either ropivacaine 0.75% or mepivacaine 1.5%. Time required for onset of sensory
      and motor block, resolution of motor blockade, onset of postsurgical pain, and
      time of first analgesic medication were recorded. RESULTS: The 2 groups were
      similar with regard to demographic variables and duration of surgery. Onset of
      sensory and motor block was significantly shorter in the mepivacaine group (9.9
      +/- 3.3 min and 14.7 +/- 3.6 min, respectively) than in the ropivacaine group
      (18.1 +/- 6.1 min and 23.6 +/- 5.5 min, respectively) (P < 0.001). Resolution of
      motor block occurred later in the ropivacaine group than in the mepivacaine group
      (P < 0.001), and duration of postoperative analgesia was significantly longer in
      the ropivacaine group (19 +/- 3.4 h) compared with the mepivacaine group (5.9 +/-
      1.1 h) (P < 0.001). Analgesic requirements were higher in mepivacaine group than
      in the ropivacaine group (P < 0.001). There were 2 failed blocks, one in each
      group. CONCLUSIONS: Both ropivacaine and mepivacaine provided effective sciatic
      nerve blockade. Mepivacaine 1.5% displayed a significantly shorter onset time
      than ropivacaine 0.75%. Postoperatively, ropivacaine 0.75% resulted in longer
      lasting analgesia and less need for oral pain medication.

PMID- 14634942
TI  - A preoperative retrobulbar block in patients undergoing scleral buckling reduces
      pain, endogenous stress response, and improves vigilance.
AB  - BACKGROUND AND OBJECTIVES: This study aims to test postoperative analgesia by
      using retrobulbar block in patients with retinal detachment surgery. METHODS:
      Twenty-nine patients scheduled for scleral buckling were included in this double
      blind, randomized, prospective study. After induction of general anesthesia and
      opening of the conjunctiva, patients received either 4 mL bupivacaine 0.5% or 4
      mL saline 0.9% injected into the retrobulbar space preoperatively. Heart rate and
      blood pressure were documented before the start of anesthesia, 10 and 50 minutes
      later, and 60 minutes after completion of surgery. At the same time points, 10 mL
      of blood were withdrawn for measurement of glucose and cortisol levels to
      evaluate the efficacy of retrobulbar block in eliminating humoral response.
      Postoperative scores for pain and vigilance were recorded 1, 6, and 24 hours
      after completion of surgery. The application of analgesic and antiemetic drugs
      was documented, as well as occurrence of nausea and vomiting. RESULTS: A
      preoperative retrobulbar block in patients undergoing scleral buckling reduces
      pain, endogenous stress response, and improves vigilance. CONCLUSIONS: Because
      the analgesic effect of the retrobulbar block was considerably longer than
      pharmacologically expected, the combined retrobulbar and general anesthesia
      "protects" against postoperative pain and is recommended for patients undergoing
      scleral buckling.

PMID- 14634943
TI  - Retroperitoneal abscess after neurolytic celiac plexus block from the anterior
      approach.
AB  - BACKGROUND AND OBJECTIVES: The anterior approach for celiac plexus block has the
      potential risks of infection, hemorrhage, and fistula formation. We report a case
      of a patient who developed a retroperitoneal abscess with the formation of a
      vascular-enteric fistula after a neurolytic celiac plexus block from the anterior
      approach. CASE REPORT: A 60-year-old female with a history of pain secondary to
      chronic idiopathic calcifying pancreatitis (VAS 7-8) underwent a subtotal
      resection of the head of the pancreas with an end-to-side pancreatojejunostomy
      using a Roux-en-Y loop. Pain continued secondary to chronic pancreatitis. Because
      of intolerance (vomiting and constipation) of morphine and transdermal fentanyl
      over a 2-month period, it was decided to perform a neurolytic celiac plexus block
      using the anterior approach with ultrasound guidance. The patient's pain was
      completely relieved, enabling withdrawal of oral analgesics. Pain reappeared
      after 2 years, and the same technique was repeated. Ten days later, she was
      admitted with diabetic ketoacidosis and lower gastrointestinal bleeding. Computed
      tomography showed a left paravertebral retroperitoneal abscess; arteriography
      suggested a fistula between the mesenteric vein and the jejunum. Urgent surgery
      was undertaken, revealing a leak of the pancreatojejunostomy and a large abscess
      around the celiac plexus. A distal pancreatectomy and partial resection of the
      Roux-en-Y loop was performed. The patient was discharged 1 month later in good
      clinical condition. Because of recurrent pain, she has required repeated
      neurolytic celiac plexus blocks via a posterior approach without complications.
      CONCLUSION: The posterior approach for neurolytic celiac plexus block should be
      considered in particular in patients with previous pancreatic surgery.

PMID- 14634944
TI  - Epidural hematoma after thoracic epidural catheter removal in the absence of risk
      factors.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this report is to enhance awareness
      that an epidural hematoma can occur even in patients devoid of risk factors. CASE
      REPORT: A 69-year-old, 55-kg male was scheduled for video-assisted thoracoscopic
      resection of bilateral pulmonary metastases and received combined thoracic
      epidural and general anesthesia. The epidural catheter insertion was
      unremarkable. All laboratory values were within normal values. No anticoagulation
      or antiplatelet drugs were administered. The epidural catheter was removed on
      postoperative day 2. The patient developed signs of an epidural hematoma a few
      hours later and was treated by decompressive laminectomy. Full neurologic
      recovery was observed after a 6-month period. CONCLUSION: Catheter removal is a
      critical period for epidural hematoma formation even if no risk factors are
      identified. Early recognition and treatment are essential features for good
      neurologic recovery after an epidural hematoma.

PMID- 14634945
TI  - Pleural effusion and chest pain after continuous interscalene brachial plexus
      block.
AB  - OBJECTIVE: We describe a unique case of a patient who experienced atelectasis of
      the lower lobe of the left lung and pleural effusion manifested by chest pain
      after continuous interscalene brachial plexus block for postoperative analgesia.
      CASE REPORT: A 45-year-old man with no respiratory disease was scheduled for left
      shoulder arthroscopy for rotator cuff repair under interscalene brachial plexus
      block and sedation. A continuous interscalene brachial plexus block provided
      postoperative analgesia. On the first postoperative day, the patient reported
      left-sided chest pain. The chest x-ray showed elevation of the left hemidiaphragm
      associated with a left lower lobe atelectasis and a minor pleural effusion. After
      catheter removal, clinical and radiologic signs resolved within few days without
      sequela. CONCLUSION: If chest pain presents after interscalene brachial plexus
      block, early postoperative chest x-ray is recommended to rule out pneumothorax,
      atelectasis, and/or pleural effusion secondary to ipsilateral phrenic block.

PMID- 14634947
TI  - Gaston Labat Lecture 2003: Labat's legend--are we doing it justice?

PMID- 14634948
TI  - Hoffman's glasses: evidence-based medicine and the search for quality in the
      literature of interventional pain medicine.

PMID- 14634949
TI  - Procedural pain in children: evidence-based best practice and guidelines.

PMID- 14634950
TI  - Cognitive-behavioral approach to the treatment of chronic pain patients.
AB  - BACKGROUND AND OBJECTIVES: Chronic pain is both prevalent and costly. Despite
      advances in understanding the anatomy, physiology, and biochemistry of
      nociception and development of potent analgesic agents and advanced technology, a
      significant number of people continue to experience pain and related disability.
      The perception of and response to pain are influenced by cognitive, affective,
      and behavioral factors as well as physical pathology. In this article, a
      selective review of research supporting the important contributions of
      psychologic factors is provided, a cognitive-behavioral perspective to
      understanding pain is presented, an integrative treatment and rehabilitation
      approach based on this perspective is described, and some of the evidence
      supporting the effectiveness of this treatment approach is summarized.
      CONCLUSION: Chronic pain by definition persists over a long period-it is a
      chronic disease. Even the most sophisticated treatments are incapable of
      eliminating all pain for all pain sufferers. There is also tremendous variation
      in how patients respond to treatments provided and prescribed. Better treatment
      outcomes are likely to occur when the psychologic contributors and the physical
      factors involved are addressed. Moreover, a treatment approach based on the
      cognitive-behavioral perspective should help patients adapt to residual pain that
      remains after currently available treatments are undertaken. Thus cognitive
      behavioral treatments should be viewed as important complements to more
      traditional pharmacological, physical, and surgical interventions.

PMID- 14634958
TI  - [Research and development. The value of patents].
AB  - The goal of innovative basic applied research is the award of patents for
      products and processes. Patents protect the exclusive use of these products and
      processes. Because of the high cost of research, it is important for governments
      to stimulate the creativity of researchers and provide economic incentives for
      them to develop patentable intellectual property. In the United States, an
      exchange program exists between the academic researchers and industry. This easy
      exchange of ideas is not adequately supported in Europe, especially in Italy. To
      further hinder researchers, the European Union has not yet passed legislation on
      patents.

PMID- 14634959
TI  - [What type of neprologist for the beginning of the third millennium?].
AB  - During the last 10-15 years the International, but especially, the American
      Nephrology have been more and more colonized by the basic sciences. This has led
      to advocate for the future a nephrologist oriented towards the basic sciences.
      While nobody would deny that the basic sciences will be useful for the
      development of nephrolologic knowledge in the next decades, there are very urgent
      clinical problems in the present that should alert against this attitude. The
      most actual problem is represented by the new kind of patients affected by renal
      diseases who are older and much more complicated than in the past. Furthermore,
      todays patients need to interact with the clinician and require to be informed
      about the diagnostic and therapeutic procedures proposed. Although it is obvious
      that a deep knowledge in the basic sciences may be useful in improving the
      clinical care, the existing situation makes it impossible to propose a
      nephrologist being able at the same time to take care of all clinical and
      relational problems of patients with renal diseases and also to be well oriented
      in the basic sciences. This imposes a choice: If the aim of nephrologist involved
      in the clinical care is directed to the development of nephrologic knowledge to
      be applied in the next decades, then it may be reasonable to have more and more
      people oriented towards the basic sciences. On the contrary, if the aim of
      nephrologist is directed to offer the best available care to the patients, then
      there is no choice: no chance for a basic sciences oriented nephrologist.

PMID- 14634960
TI  - [The research project: financing and management].
AB  - Basic and clinical research is accomplished by projects. The design of a project
      is not only based on the scientific content but also on its financing and
      management. This article wants to illustrate the correct modalities for project
      financing and project management in a scientific project.

PMID- 14634961
TI  - [Integrin Beta 3 PlA1/PlA2 polimorphism does not contribute to complications in
      both type 1 and type 2 diabetes].
AB  - BACKGROUND: The glycoprotein IIIa (beta3 integrin) is an integral part of two
      glicoprotein receptors of platelets and, respectively, endothelium and vascular
      smooth muscle cells. The gene encoding the GPIIIa, a receptor for fibrinogen, vWF
      and fibronectin, shows polymorphism (PlA1/PlA2); the PlA2 allele has been
      associated with myocardial infarction, stroke and cardiovascular disease.
      METHODS: Seven hundred and thirty-two subjects with type 1 diabetes and 605
      subjects with type 2 were recruited. The prevalence of complications in type 1
      diabetes was: microalbuminuria (uA) 17%, overt nephropathy (MA) 10%; background
      retinopathy (bR) 27%, proliferative retinopathy (pR) 22%; hypertension (HYP) 13%;
      coronary heart disease (CHD) 9%. The respective figures for type 2 diabetes were:
      uA 34%, MA 21%; bR 38%, pR 18%; HYP 80%; CHD 26%. A 247 bp fragment (exon 2) was
      amplified by PCR. For the detection of the point mutation CDGE (Constant
      Denaturing Gel Electrophoresis) after optimum denaturing conditions setting by
      DGGE (Denaturing Gradient GE) and/or RFLP by NciI digestion were employed.
      RESULTS: In type 1 diabetes, PlA1PlA1/PlA1PlA2 distribution was 77/23%. No
      differences were found among normoalbuminuric (nA: 76/24%), microalbuminuric (uA:
      79/21%) and macroalbuminuric subjects (MA: 75/25%, p=0.79) as well as among
      subjects with no retinopathy (Ret-) (74/26%), bR (76/24%) and pR (78/22%,
      p=0.81), and between HYP- (78/22%) and HYP+ (72/28%, p=0.27) as well as CHD-
      (76/24%) and CHD+ (75/25%, p=0.72). Systolic blood pressure, HbA1c and
      retinopathy were independent predictors of nephropathy. No contribution of
      diastolic BP, sex, BMI, duration of diabetes and PlA2 allele was found for the
      risk of nephropathy. In type 2 diabetes, PlA1PlA1/PlA1PlA2/PlA2PlA2 distribution
      was 74.4/23.3/2.3%, with no differences foud among nA (73/25/2%), uA (75/23/2%)
      and MA (81/17/2%, p=0.66). No significant difference was detected among subjects
      with Ret- (74/22/4%), bR (77/22/1%) and pR (77/22/1%, p=0.62). Also, no
      differences were found between HYP- (81/17/2%) and HYP+ (74/24/2%, p=0.28) as
      well CHD- (76/22/2%) and CHD+ (74/24/2%, p=0.93). Systolic BP, HbA1c, presence of
      retinopathy, gender and BMI were independent predictors of nephropathy. Diastolic
      BP, duration of diabetes and PlA2 allele did not contribute to the risk of
      nephropathy. CONCLUSIONS: The PlA1/PlA2 polymorphism of the GPIIIa gene does not
      contribute to the development of nephropathy or retinopathy in type 1 and type 2
      diabetes. Furthermore, no association was found between the PlA1/PlA2
      polymorphism, hypertension, and coronary heart disease.

PMID- 14634962
TI  - [Natural history of hepatitis C virus infection in dialysis].
AB  - Dialysis patients remain at risk for acquiring hepatitis C virus (HCV) infection.
      The issue of the natural history of HCV infection among patients undergoing long
      term dialysis is surrounded by great controversy. An accurate assessment of the
      clinical outcomes of HCV in end-stage renal disease (ESRD) is hampered by
      numerous items, namely the primary features of the disease: its onset is rarely
      recognized and its course is prolonged exceedingly. Viral, host, and/or
      environmental factors may influence the outcome of chronic HCV infection but
      their precise role in promoting disease progression are yet to be defined in
      dialysis patients. It is well known that HCV-related liver disease usually runs
      an asymptomatic course and the liver-related mortality in the dialysis population
      is very low. In addition, it has been suggested that the HD procedure may exert a
      protective effect on the course of HCV and several mechanisms have been advocated
      to this purpose. However, the rate of persistence of HCV after acute hepatitis C
      is probably extremely high among dialysis patients. Recently a strong and
      independent relationship between HCV status and survival in the dialysis
      population has been observed. The frequency of liver cancer in dialysis patients
      appears higher than that seen in the general population. These findings have been
      obtained by several prospective studies with adequate size and long follow-ups.
      The natural history of HCV in patients on long-term dialysis will be better
      defined as more data are generated from ongoing studies. Dialysis patients
      desperately need effective and safe antiviral agents for the treatment of HCV
      related liver disease.

PMID- 14634963
TI  - [Evaluation of quality of life by improving the uraemic anaemia status].
AB  - BACKGROUND: Anaemia is one of the most common signs of chronic uraemia that
      determines an increase in both morbidity and mortality, as well as a
      deterioration in the quality of life of affected patients. We evaluated the
      impact of the application of the European Best Practice Anaemia Guidelines to the
      quality of life of dialysed patients. PATIENTS AND METHODS: We studied for 12
      months (from December 2000 to November 2001) 62 patients in haemodialysis and 22
      patients in peritoneal dialysis. For the statistical analysis the following
      parameters were examined: haemoglobin levels, TSAT, and weekly doses of Epo. To
      assess the quality of life we asked the patients, at the initial visit and 12
      months after treatment, to fill out the "Medical Outcome Study Short Form 36
      items Heath Survey" and "Kidney Disease Quality of Life". RESULTS: The
      significant increase in TSAT levels attained in haemodialysed patients (p = 0.03)
      induced an increase in haemoglobin levels and consequent reduction in EPO
      administration (p = 0.04). During the study, a significant improvement in General
      Health (GH) (p = 0.03) was observed. At the end of the treatment, Physical
      Functioning (PF) (p = 0.04), Role and Physical Health (RP) (p = 0.02) and Social
      Functioning (SF) (p = 0.005) showed significant variations. CONCLUSIONS: The
      application of the European Best Practice Anaemia Guidelines improves the
      management of anaemia and the Global Health Assessment in uraemic patients. These
      data demonstrate how inappropriate anaemia management can negatively affect the
      quality of life of these patients and increase the medical costs.

PMID- 14634964
TI  - [Homocysteine, folate therapy and outcome in hemodialysis: results from a
      prospective study].
AB  - BACKGROUND: Despite the well-known effectiveness of folate therapy on
      hyperhomocysteinemia in hemodialysis, its benefits on outcome are still unclear.
      METHODS: Sixty-five patients on thrice-weekly maintenance hemodialysis lasting
      more than 3 months were followed up for 1 year after stratification by
      predialysis homocysteine level (tHcy). Parenteral folate (25 mg quarterly) and
      cobalamine (1 mg quarterly) therapy was started only if the tHcy levels were > 30
      uM/L at baseline or at scheduled retests (every 7 months). End points were
      overall mortality and new ischemic events (affecting heart, brain, or lower
      extremities). RESULTS: 58.5% of patients received treatment at baseline and
      achieved a 60% reduction of tHcy. 38.1% progressed to levels of over 30 tHcy at 6
      months and were placed on treatment. No other major changes occurred until the
      end of the study. An excess of both overall mortality (30.8% versus 12.1%; p =
      0.075) and vascular morbidity (38.5% versus 12.1%; p = 0.03) occurred in
      initially untreated patients,those presenting without baseline intermediate to
      severe hyperhomocysteinemia. CONCLUSIONS: In undertaking hemodialysis, it appears
      that treating intermediate to severe hyperhomocysteinemia carries better
      prognosis for outcome than untreated moderate or absent hyperhomocysteinemia. It
      is uncertain if the benefit of therapy is valid, or if it is confounded by an
      association between lower tHhy and hidden malnutrition or concomitant diseases.

PMID- 14634965
TI  - [Side effects and toxicity of immunosuppressive agents].
AB  - The toxicity and side effects of immunosuppressive drugs currently used in the
      clinical practice of renal transplantation are examined. Different
      immunosuppressive drugs act during different points of T-cell maturation, thus
      allowing the concomitant association of different drugs to reduce clinical
      toxicity. Immunosuppressive drugs have two kinds of toxicity: "therapeutic
      toxicity" and "nontherapeutic toxicity". Only the latter is the topic of this
      review. A similar toxicity profile is shared by various immunosuppressive drugs.
      In planning treatments, drugs must be chosen based on their toxicity profile and
      their adequate effect on the clinical syndrome being treated. The main
      calcineurine inhibitors (CNI) side effects are nephrotoxicity, cardiotoxicity,
      and post transplant diabetes mellitus (PTDM). Steroids have multiple side
      effects, the most important of which are negative effects on bone and
      cardiovascular function. New drug trials have been undertaken to find
      immunosuppressive drugs with lower toxicity and less negative impact on bone and
      cardiovascular function. In preliminary studies, Sirolimus seems to have a less
      severe side effects profile.

PMID- 14634966
TI  - [Causality in nephrology: study design and objectives of future research].
AB  - BACKGROUND: Causality has to be assessed by randomised controlled trials.
      However, since these are not always ethically or technically possible, other
      study designs such as cohort studies, case-control and cross-sectional analytic
      studies may be used. METHODS: In this review, we focus on the strengths and
      limitations of epidemiological studies whose aim is to identify the causal
      relationship between study factor and outcome (cohort studies, case-control
      studies, cross-sectional analytic studies). We also introduce the absolute and
      non-absolute parameters useful in determining the causal relationship in
      epidemiological studies. RESULTS: To establish a causal relationship between a
      factor and an outcome, exposure must precede the outcome, the association must
      not be due to chance, bias, confounding or misclassification. It is important
      when reading this kind of research papers that all these factors are properly
      considered. Studies in which strong associations are documented, whereby a dose
      effect relationship exists, and those which are consistent with the results of
      previous epidemiological studies and document biologically plausible associations
      are generally stronger evidence than those in which these criteria are not found.
      CONCLUSIONS: The design and conduct of valid cohort, case-control and other type
      of studies, when randomised trials are unfeasible or unethical to answer
      causality and intervention questions, is a challenge for the nephrology
      community, presently lacking valid clinical evidence and adequate answers to many
      questions.

PMID- 14634967
TI  - [Historical Archives of Italian Nephrology. Goldblatt, kidney and hypertension:
      three steps in the history of nephrology].
AB  - The existence of a clear relationship between renal ischemia and hypertension has
      been widely documented by Harry Goldblatt and his colleagues. In their original
      papers they showed that gross and persistent elevation of systolic blood pressure
      could be produced in dogs by clamping both renal artery, or one if the other
      kidney had been removed. If renal arteries constriction was not too severe, a
      stable hypertension unaccompanied by more than mild renal impairment was
      produced. Subsequently, Goldblatt showed that, with severe constriction, retinal
      changes, arteriolar impairment and left ventricular hypertension could occur.
      Goldblatt has remained steadily of the opinion that essential hypertension in man
      is similarly due to renal ischemia occasioned either by stenosis of a main
      artery, or by organic changes in the smaller renal arteries down to the size of
      the different glomerular arteries. At first sight, it might seem like a simple
      matter to correctly identify the chain of events that begins with renal artery
      constriction and ends with persistent hypertension. Observing that a link was
      missing in this chain of events, Goldblatt hypothesised that the link was a
      humoral mechanism. Tigersted and Bergman showed that renin was the missing link.
      Renal ischemia as cause of hypertension in dogs opened a new chapter in the
      connection between kidney circulation and blood pressure elevation. This quite
      unexpected connection is one of the most challenging issues today and clearly
      demonstrates that the development of Goldblatt's ideas on renal circulation is
      still important and has by no means ended. Goldblatt, in his epistemologic
      approach to hypertension scientific challenges, realised that ideas are the
      building blocks of science: not flights of fancy, not notions sculpted in snow,
      but enduring concepts. Goldblatt's lasting ideas are more than a function of time
      and place: they have inherent qualities that have survived up to the present day.

PMID- 14634968
TI  - [Pregnancy during nephropathy].
AB  - We illustrate two cases of pregnancy complicated by previously onset chronic
      nephropathy. In spite of two completely different pathogenetic mechanisms for
      chronic renal insufficiency (IgA nephropathy in one case and vescico-ureteral
      reflux in the other), renal function at the beginning of the pregnancy was
      similar and only partially impaired. In either case the pregnancy lowered by 50%
      the residual glomerular filtration rate. Only minimum recovery was observed
      during several months of follow-up.

PMID- 14634969
TI  - [An exceptionally severe hyperuricemia in acute renal failure caused by
      spontaneous tumor lysis syndrome (TLS)].
AB  - Acute tumor lysis syndrome (TLS) is a catastrophic complication of the treatment
      of certain neoplastic disorders. It most commonly occurs in association with
      hematologic malignancies and manifests a few hours to a few days after initiation
      of specific chemotherapy. Acute spontaneous TLS has been described in leukemia
      and lymphoma and in some patients with solid tumors prior to institution of
      therapy. The findings that may be seen in acute TLS include hyperphosphatemia,
      hypocalcemia, hyperuricemia, hyperkalemia, and acute oliguric or anuric renal
      failure due to uric acid precipitation within the tubules (acute uric acid
      nephropathy) and to calcium phosphate deposition in the renal parenchyma and
      vessels. We report here a case of acute spontaneous TLS (high grade B-cell
      lymphoma of the right colon) in which serum uric acid concentration attained
      exceptionally high levels (36.7 mg/dL). The patient underwent acute oliguric
      renal failure soon after right colectomy. He was treated by means of a large
      infusion of saline. The renal function recovered in such a rapid way that no
      dialysis treatment was required. In conclusion the present case report has two
      peculiarities: that of being one of the rare examples of spontaneous TLS, and
      that of showing an exceptionally severe hyperuricemia, probably the highest ever
      reported in the literature. The administration of a large volume of saline was
      able to ensure a complete recovery of renal function. Therefore, hydration with
      saline remains the keystone in the prevention and treatment of acute TLS.

PMID- 14634970
TI  - Trends in elective terminations of pregnancy between 1989 and 2000 in a French
      county (the Isere).
AB  - OBJECTIVES: This study was performed in order to provide a description of
      indications for induced elective terminations of pregnancy (ETOP), their
      characteristics (e.g. gestational age), and their evolution over time. DESIGN OF
      THE STUDY: This is an epidemiological study. The geographic area covered is the
      French county of 'Isere', which represents a mean of 14 000 births per year over
      the study period. MATERIALS AND METHODS: Data on ETOPs were collected actively
      from medical records by a register of childhood deficiencies and adverse
      perinatal events in this county. Between 1989 and 2000, 996 ETOPs were notified.
      RESULTS: Four main grounds for ETOPs were identified: (1) morphological anomalies
      with normal karyotype (39%), (2) chromosomal anomalies (35%), (3) other fetal
      grounds (16%), and (4) maternal indications (10%). Prevalence rates for the first
      two grounds increased significantly over the study period respectively from 2.0
      to 2.9 and from 1.4 to 2.7 per 1000. Among the ETOPs carried out because of fetal
      indications, the percentage of late ETOPs (from 24 weeks of gestation) was 34.6%,
      and remained stable over the studied period. In some cases, a medical consensus
      was not reached with respect to indications for termination (sex chromosome
      anomalies, limb defects). We estimated the percentage of these cases as being
      2.7% of the figure for fetal indications, without any variation in prevalence
      over the whole period (p = 0.59). The increasing number of ETOPs that occurred in
      the chromosomal aberrations group during the study period is thought to be due to
      an increase in diagnostic sensitivity. The increase that occurred in the
      morphological anomalies group is thought to be due both to an increase in
      sensitivity and to a widening of the field with respect to indications, some of
      which have an uncertain prognosis (e.g. agenesis of the corpus callosum).
      CONCLUSION: This study provides useful data for monitoring medical practice
      consistency within the field of prenatal diagnosis, and for the drive to keep
      medical practice within ethically acceptable limits.

PMID- 14634971
TI  - Prenatal diagnosis of carnitine palmitoyltransferase 2 deficiency in chorionic
      villi: a novel approach.
AB  - Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common autosomal
      recessive inherited disease of the mitochondrial long-chain fatty acid (LCFA)
      beta-oxidation, may result in three distinct clinical phenotypes, namely, a mild
      adult muscular form, a severe infantile hepatocardiomuscular disease, and a
      neonatal form, which includes dysmorphic features in addition to
      hepatocardiomuscular symptoms. Both the latter forms are life-threatening
      diseases, and prenatal diagnosis (PND) can be offered to couples at a one-fourth
      risk of having an affected child. PND of CPT2 deficiency hitherto relied mostly
      on mutation detection from fresh chorionic villi (10 weeks' gestation), since
      CPT2 activity could be assayed on cultured amniocytes only (16-17 weeks'
      gestation).We devised a CPT2 activity assay from 10 mg of chorionic villi
      sampling (CVS). Combining this enzymatic assay to haplotype study using
      polymorphic markers linked to the CPT2 gene, we were able to carry out within 2
      days, CPT2 deficiency PND, in two unrelated families, using a CVS performed at
      the 11th week of gestation.

PMID- 14634972
TI  - Strict glycemic control in diabetic pregnancy-implications for second-trimester
      screening for Down syndrome.
AB  - OBJECTIVES: Studies in the early 1990s showed that the normal levels of the
      biochemical markers used to screen for Down syndrome in the second trimester of
      pregnancy differ between healthy women and women with insulin-dependent diabetes
      mellitus (IDDM). Thereafter, most laboratories adopted correcting factors to
      adjust for these differences. However, the current validity of these factors in
      light of the recent improvements in glycemic control in diabetic pregnancy has
      not been investigated. METHODS: The sample consisted of 35 pregnant women with
      strictly controlled IDDM and 40 healthy controls matched for age and gestational
      week. All women had singleton pregnancies and were followed till delivery.
      RESULTS: Comparison of the triple test results between the two groups after
      adjustment with the traditional corrective factors yielded no significant
      differences in serum levels of any of the markers (unconjugated estriol, human
      chorionic gonadotrophin, alpha-fetoprotein). CONCLUSIONS: These results suggest
      that the recent improvement in glycemic control of pregnant women with IDDM
      changes the metabolic milieu that might cause the biochemical differences with
      healthy pregnant patients.

PMID- 14634973
TI  - Charts of fetal size: kidney and renal pelvis measurements.
AB  - OBJECTIVE: To construct new size charts for fetal kidney measurements and to
      define normal limits for renal pelvic antero-posterior diameter. METHODS: A
      prospective, cross-sectional study was carried out in the ultrasound department
      of a large hospital. Six hundred and sixty-three fetuses were scanned only once
      for the purpose of the study at gestations between 14 and 42 weeks. Centiles for
      kidney dimensions were estimated by combining separate fractional polynomial
      regression models fitted to the mean and standard deviation, assuming that the
      measurements have a normal distribution at each gestational age. Centiles for
      renal pelvic diameter were obtained using quantile regression. RESULTS: Size
      charts for fetal kidney dimensions [antero-posterior (AP), transverse, length and
      volume] and renal pelvis diameter are presented and compared with previously
      published data. CONCLUSION: We present new size charts for fetal kidney size that
      take into consideration the increasing variability with gestational age. These
      data should aid the prenatal diagnosis of renal pathology by defining renal size
      and the upper limits of normal pelvic dilatation. They may be particularly useful
      in the third trimester where there is limited data available. Our data confirm
      that it is reasonable to use an upper limit of 7 mm for the AP diameter in late
      pregnancy.

PMID- 14634974
TI  - Rare cell isolation using antibodies covalently linked to slides: application to
      fetal cells in maternal blood.
AB  - We describe here a new type of method for isolation of rare cell populations in
      biological fluids. The method is based on the anthraquinone technology for
      covalent binding of molecules to a polymer surface. An anthraquinone molecule
      conjugated via a linker to an electrophilic group (AQ Immobilizer trade mark
      reagent, Exiqon A/S) is covalently bound to a polymer surface by UV irradiation.
      The electrophilic group of this AQ reagent can covalently bind a specific
      antibody directed against a specific cell marker. Applying a cell sample to the
      functional surface, the cells having the specific cell marker on the cell surface
      will bind to the antibody on the functional surface. Using this technique, even
      extremely small cell populations may be isolated. We succeeded in isolating fetal
      cells from maternal blood samples in the first trimester for chromosome defects
      genetic diagnosis.

PMID- 14634975
TI  - Detection of an aneurysm of the vein of Galen following signs of cardiac overload
      in a 22-week old fetus.
AB  - OBJECTIVES: To present early prenatal diagnosis of an aneurysm of the Vein of
      Galen by detecting signs of cardiac overload in a 22-week old fetus. CASE: We
      report on a 22-week old fetus presenting with dilation of the heart, tricuspid
      and mitral valve regurgitation, reversed flow in the aortic arch and dilated neck
      vessels. Evaluation of the fetal brain revealed a dilated left ventricle, signs
      of brain hemorrhage and an anechoic structure between the two hemispheres.
      METHODS: By using the conventional Doppler technique, an intracerebral fistula
      and dilated vein of Galen was visualized. The complex vascular structure was
      demonstrated using 3-D color power angiography (3-D CPA). To our knowledge, this
      is the earliest diagnosis of this vascular malformation. CONCLUSION: Although
      signs of cardiac overload rarely appear before the third trimester in cases of
      arteriovenous fistulae, it was shown that these signs could lead to the correct
      diagnosis of an aneurysm of the vein of Galen. Additionally, we show that 3-D CPA
      is a promising technique to visualize complex vascular structures and make them
      easier to understand.

PMID- 14634976
TI  - Meconium peritonitis and pseudo-cyst formation: prenatal diagnosis and post-natal
      course.
AB  - OBJECTIVES: Intra-uterine bowel perforation can occur secondary to a variety of
      abnormalities and cause sterile peritonitis in the fetus (generalised = type I).
      If sealing of the perforation does not take place, a thick-walled pseudo-cyst can
      form (type II). METHODS: Over a 12-year period, 21 616 pregnancies were screened
      for gastro-intestinal malformations using prenatal ultrasound. We identified 1077
      cases suspicious of surgically correctable malformations. Post-natal diagnoses
      and outcome were worked up retrospectively. RESULT: We found 96 fetuses with
      suspected gastro-intestinal malformations. Prenatal bowel perforation with
      meconium peritonitis was confirmed in 11 cases. In 5 of these 11, the correct
      diagnosis had been predicted prenatally. One child presented as a fetal and
      neonatal emergency (case report). Ten of the eleven infants were operated on
      during their first day of life. Intra-operative findings were atresia (n = 4),
      meconium ileus (n = 6) and no obvious cause (n = 1). Two children suffered fatal
      complications. CONCLUSION: Meconium peritonitis and meconium pseudo-cysts as its
      special manifestation are assessable by prenatal diagnosis but present in
      different ways. They can present as fetal ascites or echogenic bowel and cause
      fetal or neonatal distress, requiring close observation and highly specialised
      care.

PMID- 14634977
TI  - Changes in the frequency power spectrum of fetal heart rate in the course of
      pregnancy.
AB  - OBJECTIVE: The aim of this study was to examine changes in the heart rate
      variability based on the frequency power spectrum of healthy fetuses during the
      second and third trimester of pregnancy. METHODS: We analyzed 222 fetal
      magnetocardiograms recorded in 49 healthy singleton pregnancies between the 16th
      and 42nd week. Discrete Fourier transformation was performed on the time-based
      step function of the RR-intervals. Changes of spectral density in the frequency
      spectrum in various bands between 0.003 to 1 Hz, including low-frequency (LF:
      0.04-0.15 Hz) and high-frequency (HF: 0.15-0.40 Hz) bands, were examined as a
      function of gestational age. RESULTS: Spectral density between 0.003 to 1.0 Hz
      increased with gestational age with large changes, in particular, at lower
      frequencies. At approximately the 32nd week, the rate of increase in power slowed
      substantially. Prior to this time, the rates of change in power were different
      for the bands 0.003 to 0.40 Hz, 0.40 to 0.60 Hz and 0.60 to 1.0 Hz. LF and HF
      showed similar development, with HF increasing slightly more rapidly. CONCLUSION:
      We conclude that characteristic spectral bands that increase in spectral density
      at different rates during the second and third trimester may be identified. They
      most likely reflect developmental changes and behavioral states during pregnancy.

PMID- 14634978
TI  - Fetal serum alpha-fetoprotein in alloimmunised pregnancies.
AB  - OBJECTIVES: Maternal serum alpha-fetoprotein (AFP) levels have been known to be
      increased in red blood cell alloimmunisation. Since AFP is now thought be a pro
      erythropoietic factor, we wished to evaluate fetal serum levels of AFP in cases
      of alloimmunised pregnancies. METHODS: We studied AFP levels in 32 fetal serum
      samples from women with red blood cell alloimmunisation at the time of the first
      fetal blood sampling. We expressed the levels of AFP and haemoglobin as absolute
      numbers and as delta values (number of SDs by which the observed value differed
      from the normal mean for the same gestation). Main outcome measures were fetal
      serum AFP levels and fetal haemoglobin concentration. RESULTS: Overall, fetal AFP
      level was higher than normal in the cases (delta values 2.4 +/- 5.5 SD). However,
      mildly affected non-hydropic cases had higher levels than severely affected
      fetuses with hydrops. CONCLUSIONS: Fetuses affected by red blood cell
      alloimmunisation have increased levels of serum AFP but these levels fall back to
      low levels in severe anaemia especially with hydrops, which could represent the
      failing of a compensatory erythropoietic mechanism. Our results suggest that
      fetal haematopoiesis is activated early in red blood cell alloimmunisation but
      was subsequently impaired.

PMID- 14634979
TI  - Ductus venosus assessment at the time of nuchal translucency measurement in the
      detection of fetal aneuploidy.
AB  - OBJECTIVE: To assess the potential value of ductus venosus Doppler studies in the
      detection of fetal aneuploidy on measurement of nuchal translucency. METHODS: The
      pulsatility index for veins (PIV) and the lowest velocity during atrial
      contraction (A-wave) were determined in the fetal ductus venosus in 3382
      consecutive pregnancies at 10 to 14 weeks and studied from December 1996 to
      December 2001. Nuchal translucency was also measured. The population studied
      included 1664 pregnancies at high risk and 1718 at low risk for fetal aneuploidy.
      RESULTS: In relation to the prenatal detection of trisomy 21, the ductus venosus
      PIV was increased in 75% (36/48), the A-wave was decreased in 58% (28/48), and
      nuchal translucency was enlarged in 81% (39/48) of the trisomy 21 fetuses [71%
      (22/31) when nuchal translucency referrals were excluded]. The corresponding
      figures for trisomies 18 and 13 were 71, 58 and 83%, respectively, being 33, 33
      and 33% for other unbalanced anomalies. CONCLUSION: There is a high proportion of
      fetuses with trisomies 21, 18 and 13 (around 75%) in which the ductus venosus PIV
      is increased (above the 95th percentile) at 10 to 14 weeks, this proportion being
      similar to that observed for increased nuchal translucency measurement.

PMID- 14634980
TI  - Prenatal diagnosis of congenital mesoblastic nephroma in mid-second trimester by
      sonography and magnetic resonance imaging.
AB  - Although congenital mesoblastic nephroma (CMN) is a rare benign congenital renal
      tumor, it is the most common solid renal tumor in the newborn period. The most
      common presentation of congenital mesoblastic nephroma is polyhydramnios, and
      only one case with prenatal fetal hydrops has been previously reported. Prenatal
      diagnosis of CMN has previously been made on the basis of the findings of
      sonography in the third trimester, and magnetic resonance imaging (MRI)-based
      diagnosis has been reported recently. Here we report a case of prenatally
      diagnosed classical type CMN diagnosed at 22 + 3 weeks of gestation based on the
      findings of sonography and magnetic resonance imaging. The characteristic imaging
      findings in this case were fetal hydrops and polyhydramnios. To our knowledge,
      this is the youngest reported gestational age for prenatal diagnosis of CMN and
      it is the second case of CMN associated with fetal hydrops detected prenatally.

PMID- 14634981
TI  - Prenatal manifestation of superior mesenteric artery syndrome.
AB  - Intestinal obstruction is not a rarity in the newborn. Its etiology is diverse.
      Superior mesenteric artery syndrome (SMAS) is a phenomenon in which the duodenum
      is obstructed by the SMA. This causes bowel obstruction accompanied by duodenal
      dilatation. It has previously been described in adults and children but rarely in
      infants. We report for the first time on an intrauterine manifestation of SMAS.

PMID- 14634982
TI  - Possible human chimera detected prenatally after in vitro fertilization: a case
      report.
AB  - BACKGROUND: Chimerism is the coexistence of more than one cell line in an
      individual, due to the fusion of originally separate zygotes. It has been very
      rarely described in humans. METHODS: A 36-year-old woman who was referred for in
      vitro fertilization (IVF) for unexplained infertility had three embryos
      transferred. RESULTS: Four weeks and five days after the transfer, ultrasound
      examination detected a single fetus in the uterus. Ultrasound examination at 17
      weeks for metrorrhagia showed severe intrauterine growth retardation.
      Amniocentesis revealed a mixture of 46,XY and 46,XX clones. Histopathologic
      examination showed a dysmorphic fetus with female phenotype and severe growth
      retardation. CONCLUSIONS: Although demonstration by fingerprinting has not been
      possible, fusion of two of the three transferred embryos (one male and one
      female) seems to be the most probable mechanism that could explain both
      cytogenetic and histopathologic observations. No chimera has yet been described
      after IVF. It would be interesting to collect any such observations from other
      IVF centers.

PMID- 14634983
TI  - Fetal phenotype of Prader-Willi syndrome due to maternal disomy for chromosome
      15.
AB  - Prader-Willi syndrome (PWS) results from either paternal deletion of 15q11-q13,
      or maternal uniparental disomy (UPD) of chromosome 15 or imprinting center
      mutation. Prenatal diagnosis of PWS is currently indicated for chromosomal
      parental translocation involving chromosome 15 and for decreased fetal movements
      during the third trimester of gestation. Here we present the prenatal diagnosis
      of PWS during the first trimester of gestation and autopsy findings. Chorionic
      villus sampling (CVS) was performed for advanced maternal age at 13 weeks'
      gestation. CVS showed mosaicism including cells with a normal karyotype and cells
      with trisomy 15. Amniocentesis showed cells with a normal karyotype. Molecular
      analysis demonstrated that the fetus had a typical PWS abnormal methylation
      profile and maternal disomy for chromosome 15. Fetal ultrasound examination
      showed slightly enlarged lateral ventricles and hypoplasic male external
      genitalia without intra-uterine growth retardation. The autopsy showed a
      eutrophic male fetus with facial dysmorphy, hypoplasic genitalia, abnormal
      position of both feet and posterior hypoplasia of the corpus callosum. This
      report points out that in a karyotypically normal fetus with ambiguous male
      external genitalia and cerebral anomalies, extensive cytogenetic and molecular
      biology studies are strongly recommended because of risk of PWS.

PMID- 14634984
TI  - Maternal hydrops syndrome following successful treatment of fetal hydrops by
      shunting of bilateral hydrothorax.

PMID- 14634985
TI  - Prenatal exclusion of cleidocranial dysplasia.

PMID- 14634986
TI  - Prenatal ultrasonographic detection of an axillo-thoracic lymphangioma: an
      ethical dilemma.

PMID- 14634987
TI  - Counseling patients with trisomy 17 mosaicism found at genetic amniocentesis.

PMID- 14634988
TI  - Amniotic fluid embolism during late term termination of pregnancy.

PMID- 14634989
TI  - CHARMM fluctuating charge force field for proteins: I parameterization and
      application to bulk organic liquid simulations.
AB  - A first-generation fluctuating charge (FQ) force field to be ultimately applied
      for protein simulations is presented. The electrostatic model parameters, the
      atomic hardnesses, and electronegativities, are parameterized by fitting to DFT
      based charge responses of small molecules perturbed by a dipolar probe mimicking
      a water dipole. The nonbonded parameters for atoms based on the CHARMM atom
      typing scheme are determined via simultaneously optimizing vacuum water-solute
      geometries and energies (for a set of small organic molecules) and condensed
      phase properties (densities and vaporization enthalpies) for pure bulk liquids.
      Vacuum solute-water geometries, specifically hydrogen bond distances, are fit to
      0.19 A r.m.s. error, while dimerization energies are fit to 0.98 kcal/mol r.m.s.
      error. Properties of the liquids studied include bulk liquid structure and
      polarization. The FQ model does indeed show a condensed phase effect in the
      shifting of molecular dipole moments to higher values relative to the gas phase.
      The FQ liquids also appear to be more strongly associated, in the case of
      hydrogen bonding liquids, due to the enhanced dipolar interactions as evidenced
      by shifts toward lower energies in pair energy distributions. We present results
      from a short simulation of NMA in bulk TIP4P-FQ water as a step towards
      simulating solvated peptide/protein systems. As expected, there is a nontrivial
      dipole moment enhancement of the NMA (although the quantitative accuracy is
      difficult to assess). Furthermore, the distribution of dipole moments of water
      molecules in the vicinity of the solutes is shifted towards larger values by 0.1
      0.2 Debye in keeping with previously reported work.

PMID- 14634990
TI  - Peptide backbone reconstruction using dead-end elimination and a knowledge-based
      forcefield.
AB  - A novel, yet simple and automated, protocol for reconstruction of complete
      peptide backbones from C(alpha) coordinates only is described, validated, and
      benchmarked. The described method collates a set of possible backbone
      conformations for each set of residue triads from a structural library derived
      from the PDB. The optimal permutation of these three residue segments of backbone
      conformations is determined using the dead-end elimination (DEE) algorithm.
      Putative conformations are evaluated using a pairwise-additive knowledge-based
      forcefield term and a fragment overlap term. The protocol described in this
      report is able to restore the full backbone coordinates to within 0.2-0.6 A of
      the actual crystal structure from C(alpha) coordinates only. In addition, it is
      insensitive to errors in the input C(alpha) coordinates with RMSDs of 3.0 A, and
      this is illustrated through application to deliberately distorted C(alpha)
      traces. The entire process, as described, is rapid, requiring of the order of a
      few minutes for a typical protein on a typical desktop PC. Approximations enable
      this to be reduced to a few seconds, although this is at the expense of
      prediction accuracy. This compares very favorably to previously published
      methods, being sufficiently fast for general use and being one of the most
      accurate methods. Because the method is not restricted to the reconstruction from
      only C(alpha) coordinates, reconstruction based on C(beta) coordinates is also
      demonstrated.

PMID- 14634991
TI  - Improving the efficiency and reliability of free energy perturbation calculations
      using overlap sampling methods.
AB  - A challenge in free energy calculation for complex molecular systems by computer
      simulation is to obtain a reliable estimate within feasible computational time.
      In this study, we suggest an answer to this challenge by exploring a simple
      method, overlap sampling (OS), for producing reliable free-energy results in an
      efficient way. The formalism of the OS method is based on ensuring sampling of
      important overlapping phase space during perturbation calculations. This
      technique samples both forward and reverse free energy perturbation (FEP) to
      improve the free-energy calculation. It considers the asymmetry of the FEP
      calculation and features an ability to optimize both the precision and the
      accuracy of the measurement without affecting the simulation process itself. The
      OS method is tested at two optimization levels: no optimization (simple OS), and
      full optimization (equivalent to Bennett's method), and compared to conventional
      FEP techniques, including the widely used direct FEP averaging method, on three
      alchemical mutation systems: (a) an anion transformation in water solution, (b)
      mutation between methanol and ethane, and (c) alchemical change of an adenosine
      molecule. It is consistently shown that the reliability of free-energy estimates
      can be greatly improved using the OS techniques at both optimization levels,
      while the performance of Bennett's method is particularly striking. In addition,
      the efficiency of a calculation can be significantly improved because the method
      is able to (a) converge to the right answer quickly, and (b) work for large
      perturbations. The basic two-stage OS method can be extended to admit additional
      stages, if needed. We suggest that the OS method can be used as a general
      perturbation technique for computing free energy differences in molecular
      simulations.

PMID- 14634992
TI  - Theoretical study of the internal conversion of sulfoxide precursors of poly
      isothianaphthene and related polymers.
AB  - In the present contribution, we theoretically investigate the suitability of the
      sulfoxide route for the synthesis of conjugated polymers of relevance for the
      fabrication of low-band gap materials with improved characteristics. The study
      focuses specifically on the internal elimination (E(i)) reactions of sulfoxide
      precursors of model oligomers of trans- and cis-poly-isothianaphtene (PITN),
      trans-poly-isothianaphtene vinylene (PITNV), and trans-poly-(ethylene
      dioxythiophene vinylene) (PEDOTV). These reactions have been characterized in
      detail by means of Density Functional Theory, along with the MPW1K functional
      (Modified Perdew-Wang 1-parameter model for kinetics).

PMID- 14634993
TI  - DFT-GIAO calculations of 19F NMR chemical shifts for perfluoro compounds.
AB  - The (19)F NMR shieldings for 53 kinds of perfluoro compounds were calculated by
      the B3LYP-GIAO method using the 6-31G(d), 6-31+G(d), 6-31G(d,p), 6-31++G(d,p), 6
      311G(d,p), 6-311++G(d,p), 6-311G(2d,2p), 6-311++G(2d,2p), 6-311++G(2df,2p), 6
      311++G(3d,2p), and 6-311++G(3df,2p) basis sets. The diffuse functions markedly
      reduce the difference between the calculated and experimental chemical shifts.
      The calculations using the 6-31++G(d,p) basis set give the chemical shifts within
      10 ppm deviations from experimental values except for the fluorine nuclei
      attached to an oxygen atom, a four- and a six-coordinated sulfur atom, and
      FC(CF(3))(2) attached to a sulfur atom.

PMID- 14634994
TI  - Development and validation of COMPASS force field parameters for molecules with
      aliphatic azide chains.
AB  - To establish force-field-based (molecular) modeling capability that will
      accurately predict condensed-phase thermophysical properties for materials
      containing aliphatic azide chains, potential parameters for atom types unique to
      such chains have been developed and added to the COMPASS force field. The
      development effort identified the need to define four new atom types: one for
      each of the three azide nitrogen atoms and one for the carbon atom bonded to the
      azide. Calculations performed with the expanded force field yield (gas-phase)
      molecular structures and vibrational frequencies for hydrazoic acid,
      azidomethane, and the anti and gauche forms of azidoethane in good agreement with
      values determined experimentally and/or through computational quantum mechanics.
      Liquid densities calculated via molecular dynamics (MD) simulations were also in
      good agreement with published values for 13 of 15 training set compounds, the
      exceptions being hydrazoic acid and azidomethane. Of the 13 compounds whose
      densities are well simulated, nine have experimentally determined heats of
      vaporization reported in the open literature, and in all of these cases, MD
      simulated values for this property are in reasonable agreement with the published
      values. Simulations with the force field also yielded reasonable density
      estimates for a series of 2-azidoethanamines that have been synthesized and
      tested for use as hydrazine-alternative fuels.

PMID- 14634995
TI  - Ab initio direct dynamics studies on the reaction of H atom with CH3CH2Cl.
AB  - The multiple channel reaction H + CH(3)CH(2)Cl --> products has been studied by
      the ab initio direct dynamics method. The potential energy surface information is
      calculated at the MP2/6-311G(d,p) level of theory. The energies along the minimum
      energy path are further improved by single-point energy calculations at the
      PMP4(SDTQ)/6-311+G(3df,2p) level of theory. For the reaction, four reaction
      channels (one chlorine abstraction, one alpha-hydrogen abstraction, and two beta
      hydrogen abstractions) have been identified. The rate constants for each reaction
      channel are calculated by using canonical variational transition state theory
      incorporating the small-curvature tunneling correction in the temperature range
      298-5000 K. The total rate constants, which are calculated from the sum of the
      individual rate constants, are in good agreement with the experimental data. The
      calculated temperature dependence of the branching fractions indicates that for
      the title reaction, H-abstraction reaction is the major reaction channel in the
      whole temperature range 298-5000 K.

PMID- 14634997
TI  - Testing electronic structure methods for describing intermolecular H...H
      interactions in supramolecular chemistry.
AB  - In this article a wide variety of computational approaches (molecular mechanics
      force fields, semiempirical formalisms, and hybrid methods, namely ONIOM
      calculations) have been used to calculate the energy and geometry of the
      supramolecular system 2-(2'-hydroxyphenyl)-4-methyloxazole (HPMO) encapsulated in
      beta-cyclodextrin (beta-CD). The main objective of the present study has been to
      examine the performance of these computational methods when describing the short
      range H. H intermolecular interactions between guest (HPMO) and host (beta-CD)
      molecules. The analyzed molecular mechanics methods do not provide unphysical
      short H...H contacts, but it is obvious that their applicability to the study of
      supramolecular systems is rather limited. For the semiempirical methods, MNDO is
      found to generate more reliable geometries than AM1, PM3 and the two recently
      developed schemes PDDG/MNDO and PDDG/PM3. MNDO results only give one slightly
      short H...H distance, whereas the NDDO formalisms with modifications of the Core
      Repulsion Function (CRF) via Gaussians exhibit a large number of short to very
      short and unphysical H...H intermolecular distances. In contrast, the PM5 method,
      which is the successor to PM3, gives very promising results. Our ONIOM
      calculations indicate that the unphysical optimized geometries from PM3 are
      retained when this semiempirical method is used as the low level layer in a QM:QM
      formulation. On the other hand, ab initio methods involving good enough basis
      sets, at least for the high level layer in a hybrid ONIOM calculation, behave
      well, but they may be too expensive in practice for most supramolecular chemistry
      applications. Finally, the performance of the evaluated computational methods has
      also been tested by evaluating the energetic difference between the two most
      stable conformations of the host(beta-CD)-guest(HPMO) system.

PMID- 14634996
TI  - Systematic quantum chemical study of DNA-base tautomers.
AB  - The relative energies of the energetically low-lying tautomers of pyridone,
      cytosine, uracil, thymine, guanine, and iso-cytosine are studied by a variety of
      different quantum chemical methods. In particular, we employ density functional
      theory (DFT) using the six functionals HCTH407, PBE, BP86, B-LYP, B3-LYP, and BH
      LYP, and the ab initio methods Hartree-Fock (HF), standard second-order Moller
      Plesset perturbation theory (MP2), an improved version of it (SCS-MP2), and
      quadratic configuration interaction including single and double excitations
      (QCISD) and perturbative triple corrections [QCISD(T)]. A detailed basis set
      study is performed for the formamide/formamidic acid tautomeric pair. In general,
      large AO basis sets of at least valence triple-zeta quality including f-functions
      (TZV) are employed, which are found to be necessary for an accurate energetic
      description of the various structures. The performance of the more approximate
      methods is evaluated with QCISD(T)/TZV(2df,2dp) data taken as reference. In
      general it is found that DFT is not an appropriate method for the problem. For
      the tautomers of pyridone and cytosine, most density functionals, including the
      popular B3-LYP hybrid, predict a wrong energetic order, and only for guanine, the
      correct sequence of tautomers is obtained with all functionals. Out of the
      density functionals tested, BH-LYP, which includes a rather large fraction of HF
      exchange, performs best. A consistent description of the nonaromatic versus
      aromatic tautomers seems to be a general problem especially for pure, nonhybrid
      functionals. Tentatively, this could be assigned to the exchange potentials used
      while the functional itself, including the correlation part, seems to be
      appropriate. Out of the ab initio methods tested, the new SCS-MP2 approach seems
      to perform best because it effectively reduces some outliers obtained with
      standard MP2. It outperforms the much more costly QCISD method and seems to be a
      very good compromise between computational effort and accuracy.

PMID- 14634998
TI  - New reaction simulator "LUMMOX" and its application for prediction of catalytic
      activities.
AB  - We developed a new reaction simulator, "LUMMOX." It is an intermolecular
      interaction analyzer based on the theories of paired interacting orbitals (PIOs)
      and localized frontier orbitals (LFOs) that have been developed by Fujimoto et
      al. (Fukui, K.; Koga, N.; Fujimoto, H. J Am Chem Soc 1981, 103, 196; Fujimoto,
      H.; Koga, N.; Fukui, K. J Am Chem Soc 1981, 103, 7452; Fujimoto, H.; Satoh, S. J
      Phys Chem 1994, 98, 1436). LUMMOX runs on a Windows PC and displays graphic
      representation of orbital interactions. Prediction of activities, selectivities,
      and molecular weight of olefin polymerization catalysts are presented using PIO
      analysis and LFO calculation. Not only computational chemists but also
      experimental chemists can easily use this new system for catalyst design or
      molecular design from the point of view of orbital interaction.

PMID- 14634999
TI  - Ground- and excited-state properties of DNA base molecules from plane-wave
      calculations using ultrasoft pseudopotentials.
AB  - We present equilibrium geometries, vibrational modes, dipole moments, ionization
      energies, electron affinities, and optical absorption spectra of the DNA base
      molecules adenine, thymine, guanine, and cytosine calculated from first
      principles. The comparison of our results with experimental data and results
      obtained by using quantum chemistry methods show that in specific cases gradient
      corrected density-functional theory (DFT-GGA) calculations using ultrasoft
      pseudopotentials and a plane-wave basis may be a numerically efficient and
      accurate alternative to methods employing localized orbitals for the expansion of
      the electron wave functions.

PMID- 14635000
TI  - Semiempirical PM5 molecular orbital study on chlorophylls and
      bacteriochlorophylls: comparison of semiempirical, ab initio, and density
      functional results.
AB  - The semiempirical PM5 method has been used to calculate fully optimized
      structures of magnesium-bacteriochlorin, magnesium-chlorin, magnesium-porphin,
      mesochlorophyll a, chlorophylls a, b, c(1), c(2), c(3), and d, and
      bacteriochlorophylls a, b, c, d, e, f, g, and h with all homologous structures.
      Hartree-Fock/6-31G* ab initio and density functional B3LYP/6-31G* methods were
      used to optimize structures of methyl chlorophyllide a, chlorophyll c(1), and
      methyl bacteriochlorophyllides a and c for comparison. Spectroscopic transition
      energies of the chromophores and their 1:1 or 1:2 solvent complexes were
      calculated with the Zindo/S CIS method. The self-consistent reaction field model
      was used to estimate solvent shifts. The PM5 calculations predict planar
      structure of the porphyrin ring and central position of the four coordinated
      magnesium atoms in all pigments studied, in accord with the experimental, ab
      initio, and density functional results, a significant improvement as compared to
      the older semiempirical PM3 approach. Only small differences in PM5 and B3LYP/6
      31G* or Hartree-Fock/6-31G* minimum energy geometries of the reference molecules
      were observed. Calculations show that in 1:1 solvent complexes, where the
      magnesium atom is five coordinated, the magnesium atom is shifted out of the
      plane of the porphyrin ring towards the solvent molecule, while the hexa
      coordinated 1:2 complexes are again planar. The PM5 method gives atomic charges
      that are comparable with those obtained from the Hartree-Fock/6-31G* and B3LYP/6
      31G* calculations. The single point ZINDO/S CIS calculations with PM5 minimum
      energy structure gave excellent correlations between calculated and experimental
      transition energies of the chlorophylls and bacteriochlorophylls studied. Such
      correlations may be used for prediction of transition energies of the
      chromophores in protein binding sites. Calculations also predict existence of
      dark electronic states below the main Soret absorption band in all chromophores
      studied. The results suggest that the semiempirical PM5 method is a fairly
      reliable and computationally efficient method in predicting molecular parameters
      of porphyrin-like molecules.

PMID- 14635001
TI  - Extension of the PDDG/PM3 and PDDG/MNDO semiempirical molecular orbital methods
      to the halogens.
AB  - The new semiempirical methods, PDDG/PM3 and PDDG/MNDO, have been parameterized
      for halogens. For comparison, the original MNDO and PM3 were also reoptimized for
      the halogens using the same training set; these modified methods are referred to
      as MNDO' and PM3'. For 442 halogen-containing molecules, the smallest mean
      absolute error (MAE) in heats of formation is obtained with PDDG/PM3 (5.6
      kcal/mol), followed by PM3' (6.1 kcal/mol), PDDG/MNDO (6.6 kcal/mol), PM3 (8.1
      kcal/mol), MNDO' (8.5 kcal/mol), AM1 (11.1 kcal/mol), and MNDO (14.0 kcal/mol).
      For normal-valent halogen-containing molecules, the PDDG methods also provide
      improved heats of formation over MNDO/d. Hypervalent compounds were not included
      in the training set and improvements over the standard NDDO methods with sp basis
      sets were not obtained. For small haloalkanes, the PDDG methods yield more
      accurate heats of formation than are obtained from density functional theory
      (DFT) with the B3LYP and B3PW91 functionals using large basis sets. PDDG/PM3 and
      PM3' also give improved binding energies over the standard NDDO methods for
      complexes involving halide anions, and they are competitive with B3LYP/6
      311++G(d,p) results including thermal corrections. Among the semiempirical
      methods studied, PDDG/PM3 also generates the best agreement with high-level ab
      initio G2 and CCSD(T) intrinsic activation energies for S(N)2 reactions involving
      methyl halides and halide anions. Finally, the MAEs in ionization potentials,
      dipole moments, and molecular geometries show that the parameter sets for the
      PDDG and reoptimized NDDO methods reduce the MAEs in heats of formation without
      compromising the other important QM observables.

PMID- 14635004
TI  - Detection of low copy numbers of HIV-1 proviral DNA in patient PBMCs by a high
      input, sequence-capture PCR (Mega-PCR).
AB  - An internally controlled high-input PCR method, termed HIV-1 Mega-PCR was
      developed to lower the detection limit of HIV-1 DNA polymerase chain reaction
      (PCR) and to improve its value as a complementary diagnostic test. It is based on
      PCR amplification of two target sequences in the gag gene of HIV-1 following the
      selective capture of the targeted sequence and removal of unselected DNA from up
      to 500 microg of DNA. Efficient selection and amplification was monitored by
      inclusion of two mimic plasmids. The method was evaluated with buffy coat cells
      from healthy blood donors which were spiked with blood from 106 different HIV-1
      infected individuals, and with 107 HIV-1 seronegative control buffy coats. All
      specimens from HIV-infected individuals were positive by a PCR protocol using 1
      microg of patient DNA. Amplification of 1 microg DNA of the 106 spiked, diluted
      samples resulted in 68 double positive, 14 single positive, and 24 double
      negative reactions. In the Mega-PCR, the average input was 260 +/- 84 microg DNA
      containing an estimated 1.1 +/- 0.6% of spiked patient DNA. Of the 106 samples
      tested by Mega-PCR, 102 were positive and three negative. One failed to select
      the mimic plasmid. Among the 107 negative buffy coat controls, none was false
      positive and four exhibited a failure of the internal reaction control.
      Application of HIV-1 Mega-PCR to clinical specimens from seroreverting newborns
      of HIV-infected mothers and seroindeterminate, PCR-negative specimens revealed no
      indication for HIV infection, whereas three samples from confirmed, HIV-1
      infected but PCR negative individuals showed evidence of the presence of HIV-1
      DNA. Mega-PCR lowers the detection limit of an individual analysis to
      approximately 0.01 HIV-1 DNA copies/microg of applied DNA and may help to confirm
      or exclude HIV-1-infection in difficult situations diagnostic.

PMID- 14635005
TI  - Time course of hepatitis A viremia and viral load in the blood of human hepatitis
      A patients.
AB  - The hepatitis A virus (HAV) is the most common etiological cause of acute
      hepatitis infections in humans in industrialized countries. Investigations into
      the viral load during HAV viremia, however, are rare. Therefore, correlation
      studies between viral load, biochemical, and specific serological markers have
      been undertaken. The group of sera comprised a series of multiple consecutive
      blood samples drawn from 11 patients at different times after onset of the
      disease. During the period up to 70 days after the onset of icterus, the
      individual range was at 1 x 10(3) to 3 x 10(4) HAV genome equivalents/ml. From
      day 75 until 120 after onset of the disease, the levels traced were at 10(3). In
      one case, it was possible to trace 1.25 x 10(4) genome equivalents/ml up to 180
      days after onset of icterus and in two cases even up to 408 and 490 days viral
      load levels of 5 x 10(3) and 4 x 10(4) were detected, respectively. The same sera
      were used to measure IgM class antibodies to hepatitis A virus and the total anti
      HAV. The results demonstrate that a direct correlation to peak levels of viral
      load exists with peak serum transaminase levels, but neither with peak anti-HAV
      IgM levels nor with total anti-HAV. Decreasing amounts of anti-HAV IgM tend to
      occur with decreasing amounts of HAV genome equivalents; and, vice versa,
      increasing amounts of total anti-HAV are accompanied by decreasing amounts of HAV
      genome equivalents. The longest duration of viremia was found in patients
      infected with HAV genotype IA.

PMID- 14635006
TI  - HLA phenotypes and outcomes of hepatitis B virus infection in Taiwan.
AB  - The relationship of HLA phenotype and outcome of hepatitis B virus (HBV)
      infection was studied in two ethnic groups of Taiwan: Han Chinese and Taiwanese
      Aborigines. In Han Chinese, the study groups consisted of 98 persons who tested
      both hepatitis B surface antigen (HBsAg) and anti-HBs negative (Uninfected
      Group), 324 persons who tested HBsAg negative and both anti-HBs and anti-HBc
      positive (Recovered Group), and 98 patients who tested HBsAg positive for at
      least 6 months (Chronically Infected Group). In Taiwanese Aborigines, the study
      groups consisted of 34 persons in Uninfected Group, 229 persons in the Recovered
      Group, and 138 patients in the Chronically Infected Group. All subjects were
      tested for HLA (A, B, DRB1) phenotypes by sequence-specific oligonucleotide probe
      hybridization (SSOPH). HLA-DR*0406 was significantly more frequent in the
      Recovered Group, compared with the Chronically Infected Group (P < 0.001) in Han
      Chinese. There was a significant excess of HLA-B*4001 (P = 0.045) in the
      Recovered Group, compared with the Chronically Infected Group in Taiwanese
      Aborigines. The observation that different HLA phenotypes associated with
      recovery from HBV infection in different racial groups implies that various HLA
      molecules could present different HBV epitopes to induce effective immune
      responses.

PMID- 14635007
TI  - Genetic heterogeneity of the precore and the core promoter region of genotype C
      hepatitis B virus during lamivudine therapy.
AB  - It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e
      (HBe) seroconversion has usually been associated with the development of a stop
      codon in the precore region. However, the difference between lamivudine-induced
      seroconversion and spontaneous or IFN-induced seroconversion is not known. The
      aim of this study was to investigate the correlation between the evolution of the
      precore and core promoter mutations and lamivudine-induced seroconversion. Forty
      five patients with chronic hepatitis B virus (HBV) infection who were treated
      with lamivudine for more than 1 year were enrolled. The nucleotide sequence of
      the precore and core promoter region was determined before and after treatment
      with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen
      (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of
      treatment for 1 year. Of these, eight patients (66.7%) still had precore wild
      type HBV after 1 year. After 1 year, reversion to precore wild type HBV was
      detected in 11 (64.7%) of 17 patients who had precore mutant HBV before
      treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had
      precore wild type HBV before and after treatment for 1 year. Despite the loss of
      HBeAg, two thirds of the patients still had precore wild type HBV after the 1
      year treatment. It is suggested that lamivudine-induced seroconversion differs
      from spontaneous or IFN-induced seroconversion in the change of nucleotides in
      the precore region. The reversion in the precore region may be caused by the
      difference of drug-susceptibility to lamivudine. The antiviral effect of
      lamivudine may be more effective in the precore mutant HBV than in the precore
      wild type HBV.

PMID- 14635008
TI  - Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma
      in chronic carriers.
AB  - The role of quantitative viral load in development of hepatocellular carcinoma
      (HCC) among chronic hepatitis B virus (HBV) carriers was evaluated using real
      time PCR (TaqMan PCR), a highly sensitive method for quantitative detection of
      HBV DNA. Serum samples collected at study entry from HCC cases and matched
      controls were chosen separately from ongoing prospective cohort studies in
      Senegal, West Africa, and Haimen City, China. For 14 HCC cases and 28 controls
      from Senegal, the relative risk (RR, 95% CI) of HCC was 15.6 (2.0-124.3) for
      those positive by the TaqMan PCR assay. Average length of follow-up (study entry
      to death from HCC) among cases was 2.8 (+/-1.6) years. The paired median
      difference between cases and controls was 3.8 x 10(4) virions/ml, with cases
      higher (P = 0.09). In order to clarify the relationship with lower-titer viremia,
      we selected 55 cases and 55 matched controls from the Chinese cohort all negative
      for serum HBV DNA by conventional dot blot hybridization. In this group, the RR
      associated with HBV DNA positivity by TaqMan PCR was 3.1 (1.1-9.2), with an
      average duration of follow-up of 3.3 (+/-2.1) years. The median difference in
      quantitative viremia between cases and controls was 6.0 x 10(4) virions/ml, with
      cases higher (P < 0.0001). Increased risk appeared to be confined to subjects
      with viral loads >2.3 x 10(4) virions/ml. In conclusion, HBV viremia, except
      perhaps at extremely low levels, is associated with increased risk for HCC in
      prospective studies of chronic carriers in two disparate populations.

PMID- 14635009
TI  - Changing seroepidemiology of hepatitis B, C, and D virus infections in high-risk
      populations.
AB  - Needle-sharing and sexual contact are important transmission routes of hepatitis
      B, C, and D virus (HBV, HCV, HDV) infection. This study aimed to investigate the
      current status of these viral infections among high-risk populations including
      prostitutes and intravenous (i.v.) drug users, compared with the prevalence rate
      reported previously to examine the changing seroepidemiology. Of the 916 female
      prostitutes, 79 (9%) were positive for antibody to HCV (anti-HCV), 111 (12%) were
      positive for HBV surface antigen (HBsAg), and 5 (5%) had antibody to HDV (anti
      HDV). The prevalence rate was significantly lower compared to that in 1989-1991
      (12%, P = 0.037) for HCV infection, and to that in 1988 (59%) and 1996 (40%) (P <
      0.0001) for HDV infection. Of the 494 i.v. drug users, 87 (18%) patients were
      HBsAg carriers and 12 (14%) were anti-HDV-positive. The prevalence rate of HDV
      infection was significantly lower than that reported in 1985 (79%, P < 0.0001).
      Among the 443 tested i.v. drug users, 182 (41%) were anti-HCV-positive,
      significantly lower than that in 1985 (53%, P = 0.026). Of the 263 male
      prostitutes, 11 (4%) were anti-HCV-positive, 45 (17%) were HBsAg-positive, and 7
      (16%) were anti-HDV-positive. Of the 129 illegal immigrant prostitutes, 7 (5%)
      were anti-HCV-positive, 15 (12%) were HBsAg-positive and none were positive for
      anti-HDV. In conclusion, the findings indicate a declining prevalence of HCV and
      HDV infections among drug users and prostitutes over the past 16 years. Male
      prostitutes and immigrant prostitutes are new "high-risk" populations and may
      become a reservoir for disease transmission.

PMID- 14635010
TI  - Predictive value of early HCV RNA quantitation for sustained response in
      nonresponders receiving daily interferon and ribavirin therapy.
AB  - The prognostic value of early hepatitis C virus (HCV)-RNA load was evaluated
      among nonresponder patients to previous interferon (IFN) therapy treated with
      daily IFN and ribavirin. One hundred-six nonresponders (83 men), mean age 44.8 +/
      11 years, were treated with IFN-alpha 2b 3 MU/day for 24 weeks, followed by 3 MU
      x 3/week for 24 weeks plus ribavirin 1-1.2 g/day for 48 weeks. HCV RNA was
      quantified by Versant HCV RNA 3.0 assay (Bayer). The predictive values of the
      baseline and the change in viral load at week 1, 4, and 12 for sustained
      virological responses were analyzed using receiver operating characteristic (ROC)
      curves, as well as predictive values of >2 log(10) drop from baseline by weeks 1,
      4, and 12 in combination with undetectable HCV RNA for sustained virological
      response. Thirty-two patients (30.2%) were sustained virological responders. The
      highest area under the curve was obtained at week 4. The unquantifiable HCV RNA
      level, in combination with at least a 2 log(10) drop in viral load by week 4 and
      week 12, had a negative predictive value of 96% and 97%, respectively.
      Nonresponse can be predicted as early as week 4 or week 12 in nonresponders
      treated with daily IFN and ribavirin.

PMID- 14635011
TI  - Hepatitis C virus core protein upregulates transforming growth factor-beta 1
      transcription.
AB  - The majority of persons with chronic hepatitis C virus (HCV) infection develop
      liver fibrosis. Transforming growth factor (TGF)-beta 1 plays a pivotal role in
      the pathogenesis of post-inflammatory liver scarring. To clarify the influence of
      HCV infection on liver fibrosis, a reporter assay was used to investigate the
      effect of viral proteins on TGF-beta 1 expression in human hepatoma cells. Of all
      HCV proteins investigated (core, E1/E2/p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B),
      only the core protein activated the TGF-beta 1 promoter and upregulated TGF-beta
      1 expression measured by an RNase protection assay. Bases -376 to -331 bp in the
      promoter region of TGF-beta 1 are responsible for upregulation by HCV core
      protein, and the nuclear protein that binds to this region increased with the
      stimulation of HCV core protein. Blocking the mitogen-activated protein kinase
      pathway prevented upregulation of TGF-beta 1 by HCV core protein. The
      immunological response is supposed to be a major factor to cause the secretion of
      TGF-beta 1 from non-parenchymal cells, but the results suggest that the HCV core
      protein expression may upregulate directly TGF-beta 1 transcription in
      parenchymal cells and suggest a new paradigm for exacerbation of liver fibrosis
      by HCV infection.

PMID- 14635012
TI  - Association of TNF-beta polymorphism with disease severity among patients
      infected with hepatitis C virus.
AB  - The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear.
      Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the
      pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF
      alpha and -beta genes could influence the outcome of HCV infection. The aim was
      to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I
      polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty
      two patients with histologically proven chronic hepatitis, who had raised ALT
      levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308
      promoter variant of TNF-alpha was performed by PCR with primers that incorporated
      an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction
      fragment length polymorphism, sequence specific primers were used. Polymorphism
      in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients
      and healthy controls. TNF-beta A/A allele was significantly more common (P =
      0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant
      difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF
      beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence =
      4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele.
      Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele
      as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such
      as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the
      natural course of HCV infection, in particular, the disease progression. Larger
      studies including cytokine expression profiles are needed to fully understand the
      contribution of the polymorphisms described in the pathogenesis of chronic
      hepatitis C.

PMID- 14635013
TI  - Virus-specific effector CD4+ T-cell responses in hemodialysis patients with
      hepatitis C virus infection.
AB  - Patients with chronic renal failure undergoing hemodialysis who are infected with
      hepatitis C virus (HCV) may test consistently anti-HCV negative. Because CD4(+) T
      cells provide help for antibody production virus-specific effector CD4(+) T-cell
      responses were investigated in relation to anti-HCV positivity in 15 hemodialysis
      patients grouped according to HCV antibody and viremia. CD4(+) T-cell reactivity
      was studied in peripheral blood mononuclear cells by standard lymphocyte
      proliferation assay and phenotypic/functional characterization (cell-surface
      staining/cytokine secretion) by flow cytometry. HCV-specific CD4(+) T-cell
      proliferation in viremic hemodialysis patients was weak or absent independently
      of their anti-HCV status. Virus-specific CD4(+) T-cells displayed a memory
      phenotype and showed low to undetectable capacity to secrete effector interferon
      (IFN)-gamma. Impaired activation-induced cytokine secretion appeared to be Th1
      (IFN-gamma) but not Th2 (interleukin-4)-directed and was virus-specific as
      cytomegalovirus responses were preserved. The frequency ex vivo of
      CD3(+)CD4(+)IFN-gamma(+) T-cells was independent of the HCV antibody status and
      comparable between viremic (range: 0.08-1.54%) or non-viremic (0.11-3.2%)
      hemodialysis patients and healthy donors (0.13-1.10%; P = 0.58). The numbers of
      CD3(+)CD4(+)IFN-gamma(+) T-cells augmented slightly (P = 0.047) in HCV-infected
      hemodialysis patients but markedly in only one (greater than ninefold) after HCV
      stimulation. In conclusion, hemodialysis patients show limited HCV-specific
      effector CD4(+) Th1-cell responses which nonetheless seem unrelated to the anti
      HCV status and are not more impaired due to the ongoing hemodialysis.

PMID- 14635014
TI  - Prevalence and characterization of astroviruses in Argentinean children with
      acute gastroenteritis.
AB  - Among viral agents causing gastroenteritis, human astroviruses (HAstVs) take
      second or third place, after rotaviruses and caliciviruses, as the most frequent
      cause of illness. The aims of this study were to determine the prevalence of
      HAstV infection and to characterize the circulating HAstV strains in children
      with diarrhea under 3 years of age treated between 1995 and 1998 at out- or in
      patient facilities of the children's hospital in Mendoza, Argentina. Reverse
      transcription-polymerase chain reaction (RT-PCR) and enzyme immunoassay (EIA)
      were used to detect HAstVs in stool specimens. Positive specimens were tested
      further by EIA and/or sequenced to type detected HAstV strains. HAstVs were
      detected in 40 (3.7%) of 1,070 samples that were rotavirus and calicivirus
      negative: 14 (3.5%) of 402 from outpatients and 26 (3.9%) of 668 from inpatients.
      HAstV infection tended to be more severe in children during their first year of
      life: 18 (4.7%) of 383 HAstV-positive children 0-11 months old were hospitalized
      versus 8 (2.8%) of 285 children 1 year of age or older (P = 0.29). Type 1 (HAstV
      1) was the most common type (41%), followed by HAstV-4 (25%), HAstV-2 (13%),
      HAstV-3 (13%), and HAstV-5 (8%). In this first epidemiological study of HAstV
      infection in this region, we confirmed HAstV to be a cause of severe
      gastroenteritis in children, more often among children younger than 12 months of
      age. HastV-4 caused 25% of HastV infections in Mendoza, although it has been
      detected commonly elsewhere. Distinct genetic lineages were apparent but their
      epidemiological significance remains to be demonstrated.

PMID- 14635015
TI  - Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus
      nucleocapsid protein to perinuclear regions of mammalian cells.
AB  - Crimean-Congo hemorrhagic fever virus is the causative agent of a severe disease
      throughout Africa, Europe, and Asia. Like other members of the genus Nairovirus,
      the Crimean-Congo hemorrhagic fever virus contains three genomic RNA segments,
      the small (S), medium (M), and large (L) segments. The S segment encodes the
      viral nucleocapsid protein (NP), while the M and L segments encode the
      glycoproteins and the RNA-dependent RNA polymerase, respectively. In this study,
      the site of expression and assembly of Crimean-Congo hemorrhagic fever virus NP
      in mammalian cells have been investigated. It was found that the NP is localized
      in the perinuclear region of infected cells. By using the Semliki forest virus
      expression system, it was shown that the Crimean-Congo hemorrhagic fever virus NP
      is targeted to the perinuclear region of cells in the absence of native RNA
      segments and virally encoded glycoproteins. It was also demonstrated that the
      Crimean-Congo hemorrhagic fever virus NP was not expressed as a Golgi-membrane
      associated protein. By using Cytochalasin D, an agent that disrupts actin
      filaments, it was found that actin filaments are involved in targeting the viral
      NP to perinuclear regions. We also demonstrated that disruption of actin
      filaments reduced the assembly of infectious Crimean-Congo hemorrhagic fever
      virus up to 97%. Furthermore, we showed that the NP of Crimean-Congo hemorrhagic
      fever virus NP interacts with actin.

PMID- 14635016
TI  - Onset and duration of cytomegalovirus immediate early 1 mRNA expression in the
      blood of renal transplant recipients.
AB  - Human cytomegalovirus (CMV) messenger (m) RNA expression in circulating
      leukocytes reflects directly viral activity in the human host. In this study,
      sixty-nine patients were monitored prospectively for CMV infection and mRNA
      expression during the first year after renal transplantation. Of the 69
      recipients, 58 (84%) recipients were positive for CMV immediate early 1 (IE1)
      mRNA as detected by nucleic acid sequence-based amplification. The median onset
      of IE1 expression started at day 22 after transplantation and continued for a
      median duration of 82 days. IE1 mRNA expression started significantly earlier in
      recipients who developed an active CMV infection (P = 0.001) and in mycophenolate
      mofetil (MMF) treated recipients (P = 0.002). The duration of IE1 mRNA expression
      was significantly longer in recipients that had previously an early onset of IE1
      mRNA expression (P = 0.001) and in recipients with active CMV infection (P =
      0.007). Remarkably, longer prednisolone intake was correlated with a
      significantly (P = 0.02) shorter duration of IE1 expression compared to a longer
      duration of IE1 expression in recipients with only a short prednisolone intake.
      In recipients infected with glycoprotein B (gB) type 1 CMV strains, the duration
      of IE1 expression was significantly (P = 0.04) shorter compared to recipients
      infected with non-gB type 1 CMV strains (64 days vs. 150 days). The study
      indicates that multiple factors play a role in the onset and/or duration of CMV
      IE1 mRNA expression, for example, MMF treatment, prednisolone intake, and gB type
      of the specific CMV strain. The clinical significance of these correlations
      remains to be studied in more detail.

PMID- 14635017
TI  - Intracellular localization of the Epstein-Barr virus BFRF1 gene product in
      lymphoid cell lines and oral hairy leukoplakia lesions.
AB  - A novel protein encoded by the BFRF1 gene of the Epstein-Barr virus was
      identified recently [Farina et al. (2000) J Virol 74:3235-3244], which is
      antigenic "in vivo" and expressed early in the viral replicative cycle. In the
      present study, its subcellular localization was examined in greater detail
      comparing Epstein-Barr virus (EBV) induced producing and nonproducing cell lines
      by immunofluorescence: in 12-0-tetradecanoyl phorbol-13-acetate (TPA)-induced
      Raji and B95-8 cells, as well as in anti-IgG-stimulated Akata cells, the protein
      appeared to be localized over the cell nuclear membrane. A similar nuclear
      membrane localization was observed in epithelial cells of oral hairy leukoplakia,
      a pathological manifestation of permissive EBV infection. In contrast, upon
      transfection of BFRF1 in the EBV-negative Burkitt's lymphoma cell line DG75, the
      protein was localized predominantly over the plasma membrane. The membrane
      localization was abolished when DG75 cells were transfected with a C-terminal
      deletion mutant of BFRF1 lacking the transmembrane domain. Because induced Raji
      cells do not produce virus, the above observations indicate that the nuclear
      membrane localization is not associated with viral production, but requires the
      expression of EBV genes, and suggest that additional proteins, expressed early
      during viral lytic infection, might be necessary to target the protein to the
      nuclear membrane. Immunogold electron microscopy on ultrathin cryosections of
      induced B95-8 cells showed that BFRF1 on the nuclear membranes was concentrated
      over multilayered domains representing areas of active viral replication or at
      the sites of viral budding, suggesting that BFRF1 is involved in the process of
      viral assembly.

PMID- 14635018
TI  - Suppression of generation and replication of acyclovir-resistant herpes simplex
      virus by a sensitive virus.
AB  - The role of acyclovir-sensitive herpes simplex virus (HSV) was analyzed in the
      process of its replacement by a resistant virus in vitro and in vivo in the
      aspect of acyclovir therapy. The mode of replacement of acyclovir-sensitive HSV
      with acyclovir-resistant HSV was examined by the passages of acyclovir-sensitive
      wild type HSV in Vero cells under acyclovir-treatment. The development of
      resistance was monitored more adequately by counting the number of acyclovir
      resistant viruses in 10,000 plaque forming units than by the conventional
      susceptibility assay. The resistance increased with the proportion of thymidine
      kinase-deficient (TK(-)) viruses, when the susceptibilities of acyclovir-treated
      HSV population to 5'-iodo-2'deoxyuridine and phosphonoacetic acid were examined.
      The increased resistance was due to the increased proportion of acyclovir
      resistant virus but not intermediately resistant virus. Infection with mixtures
      of TK(-) and acyclovir-sensitive strains rendered TK(-) sensitive to acyclovir,
      and virus yields were reduced to the levels of acyclovir-sensitive virus in Vero
      cells. Their yield reduction depended on the proportion of acyclovir-sensitive
      viruses and induction of TK activity. This reduction in virus yields of the
      mixture of TK(-) and acyclovir-sensitive strains was confirmed by acyclovir
      treatment in the skin of mice with cutaneous infection. Acyclovir treatment
      combined with superinfection of acyclovir-sensitive virus delayed the development
      of herpetic skin lesions due to acyclovir-resistant virus and reduced virus
      yields in the infected skin. Acyclovir-sensitive virus plays an important role in
      suppressing the generation and replication of acyclovir-resistant virus during
      acyclovir therapy.

PMID- 14635019
TI  - Herpes simplex type 1 shedding is associated with reduced hospital survival in
      patients receiving assisted ventilation in a tertiary referral intensive care
      unit.
AB  - The impact of shedding of herpes simplex virus type 1 (HSV-1) on hospital
      survival of patients receiving assisted ventilation in an adult tertiary
      referral, acute trauma intensive care unit was assessed. The study was designed
      to address a clinical impression linking HSV-1 recovery with poor survival. Two
      hundred and forty-one males and 152 females were enrolled into a longitudinal
      cohort study. Combined throat swabs and tracheal secretions were tested for HSV-1
      shedding using a nested nucleic acid amplification protocol; patients were ranked
      as nonshedders, shedders, and high-level shedders. Nonparametric analysis
      assessed the impact of shedding on hospital survival and logistic regression
      measured the confounding influence of sex, age, and the Acute Physiology, Age and
      Chronic Health Evaluation (APACHE II) score. Linear-by-linear association
      determined the influence of the level of shedding on hospital survival. The
      observed mortality rate was 113/393 (28.8%). Patients shedding HSV-1 106/393
      (27%) had a significant reduction in hospital survival 66/106 (62%) in HSV-1
      shedders compared with 217/287 (75.6%) in nonshedders (P = 0.002). This
      difference remained significant when adjusted for age and sex (P = 0.026).
      Respective mortality figures for HSV-1 shedders and nonshedders were 43/106
      (40.6%) and 70/287 (24.4%) (P = 0.002). HSV-1 shedding was associated with a
      significant reduction in hospital survival amongst patients receiving assisted
      ventilation. Hospital mortality in HSV-1 shedders was increased by 16.2% over
      nonshedders. The role of HSV-1 in this setting needs to be addressed.

PMID- 14635020
TI  - Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among
      children in areas endemic and non-endemic for Kaposi's sarcoma.
AB  - Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS).
      Several studies indicate horizontal HHV-8 transmission among children in areas
      where KS is endemic, but few studies have assessed acquisition of HHV-8 by
      children in low seroprevalence areas. Antibody screening was carried out for HHV
      8 and Epstein-Barr virus (EBV) on 787 serum specimens from children living in two
      areas where HHV-8 is not endemic, the United States (US) and Germany, and on 184
      specimens from children living in a KS-endemic area (Nigeria). For children in
      the US and Germany, the results showed low HHV-8 seroprevalence rates (3-4%).
      However, US children aged 6 months to 5 years had higher HHV-8 antibody titers
      than did 6-17-year-old children (P < 0.01), a finding consistent with more recent
      infections being detected in the younger children. Compared with seroprevalence
      rates and antibody titers in US and German children, those in Nigerian children
      were significantly higher, and seroprevalence increased with age. There was no
      evidence of cross-reactivity between assays for HHV-8 and EBV, despite the
      genetic similarity of these two herpesviruses. The data indicate that HHV-8
      transmission among children where HHV-8 is not endemic occurs, but is uncommon.
      The findings also suggest that HHV-8 antibodies, as measured by current tests,
      may not persist for long periods in populations at low risk for KS and that
      vertical transmission is rare, although longitudinal studies are necessary to
      address directly these issues.

PMID- 14635021
TI  - Prevalence of selective inhibition of HPV-16 DNA amplification in cervicovaginal
      lavages.
AB  - HPV-16 viral load has been assessed with real-time PCR assays by measuring HPV-16
      DNA and a human gene in genital samples. HPV-16 viral load measurements are thus
      based on the inference that inhibitors contained in samples will equally impede
      amplification of DNA sequences from HPV-16 and human DNA. We have previously
      shown that sample lysates can inhibit amplification of HPV-16 but not beta-globin
      DNA. In the current study, cervicovaginal lavages lysates considered adequate for
      PCR analysis by a qualitative beta-globin PCR test, were screened for the
      presence of inhibitors using internal controls (IC) for HPV-16 DNA and beta
      globin in real-time PCR assays. Of 150 lysates screened with both ICs, 12 (8%)
      contained inhibitors. Inhibition of amplification of both ICs was demonstrated in
      four of these specimens. In eight lysates, amplification of HPV-16 IC only was
      impeded. Six (50%) of these 12 lysates tested positive for HPV-16 DNA despite the
      presence of PCR inhibitors. The HPV-16 viral load increased significantly after
      dilution of 11 of 12 lysates, demonstrating the presence of inhibitors in the
      undiluted lysate. Nine (90%) of 10 samples with inhibitors that were tested after
      dilution did not demonstrate inhibitory activity. The use of internal controls in
      real-time PCR is clearly essential to determine HPV viral loads since the effect
      of inhibitors on primer-driven genomic amplification is variable.

PMID- 14635022
TI  - Aggregate content influences the Th1/Th2 immune response to influenza vaccine:
      evidence from a mouse model.
AB  - During the 2000-2001 season, a newly identified oculo-respiratory syndrome (ORS)
      was detected across Canada as an adverse effect to one influenza vaccine. The
      implicated vaccine contained a higher than expected proportion of unsplit and
      aggregated influenza virions. Clinical and epidemiologic features of ORS were
      suggestive of type 2-like influences on the immune response. We hypothesized that
      the implicated vaccine from the 2000-2001 season would induce greater Th2-like
      polarization relative to the non-implicated vaccine from the same season. Three
      groups consisting of eight mice each were either immunized with implicated
      vaccine, immunized with non-implicated vaccine or not immunized. Antigen-specific
      cellular responses were characterized based on the balance of Th2 (IL-4, IL-5)
      and Th1 (IFN-gamma) cytokines in vitro. We confirm that vaccine aggregates
      deviate the immune response to a greater Th2 cytokine pattern with potential
      implications for vaccine screening, safety, and efficacy.

PMID- 14635023
TI  - Nucleotide variation in the VP7 gene affects PCR genotyping of G9 rotaviruses
      identified in Italy.
AB  - A modified (aFT9m) and a degenerate (aFT9d) version of the rotavirus G9-specific
      primer (aFT9) allowed strains that were previously untypable, because of point
      mutations accumulating at the primer binding site, to be G typed by reverse
      transcription-polymerase chain reaction. The strains were collected during 2001
      2002 in Italy in hospitals of the Apulia region, from children affected by severe
      rotavirus-associated enteritis. Using a wide selection of G9 rotaviruses detected
      worldwide, sequencing of the G9 untypable strains, sequence comparison, and
      phylogenetic analysis showed that the Italian strains have strong genetic
      similarity (< or =99.4%) to G9 rotaviruses identified recently in many parts of
      the world and different from the old G9 strains identified during the 1980s (less
      than 90%). Genetic variation of G9 rotaviruses explains the constraints
      encountered in the typing assays and presumably accounts, together with genetic
      reassortment events, for the emergence on a global scale of the G9 serotype.

PMID- 14635024
TI  - Genetic analysis of group B human rotaviruses detected in Bangladesh in 2000 and
      2001.
AB  - Group B rotaviruses detected in Bangladesh in 2000 and 2001 were analyzed
      genetically to clarify relatedness to human group B rotaviruses reported
      previously in China and India, and to animal group B rotaviruses. VP7 gene
      sequences of the Bangladeshi group B rotaviruses (Bang373, Bang544, Bang334, and
      Bang402) were almost identical to each other and also showed high sequence
      identity to the Indian strain CAL-1 (98%) and Chinese strain adult diarrhea
      rotavirus (ADRV) (92%), while identities to bovine and murine viruses were
      considerably low (60-63%). Other genes of Bang373 and Bang544 encoding VP2, VP4,
      VP6, and NSP1 through NSP5 also showed much higher sequence identities to those
      of CAL-1 (97.7-99.4%) than to those of ADRV (89.9-93.9%). Characterization of
      nucleotide substitutions among Bang373, CAL-1, and ADRV suggested that all the
      gene segments might have evolved neutrally at similar mutation rates, while some
      of the gene segments (e.g., VP2 gene) were suggested to be more conserved than
      others. In conclusion, group B rotaviruses detected in Bangladesh represented by
      Bang373 and the Indian virus CAL-1 were considered as virtually identical viruses
      which are distinct genetically from ADRV, and it was suggested that Bang373 (CAL
      1)-like group B rotavirus (Bengali strains) might be distributed primarily in an
      area around the Bay of Bengal.

PMID- 14635025
TI  - Genetic variability of human rotavirus strains isolated from Eastern and Northern
      India.
AB  - An epidemiological study was conducted in Eastern and Northern India to determine
      the genomic diversity of rotaviruses in these parts of the country. In 2001, a
      total of 126 Group A rotavirus positive samples were detected from children below
      4 years of age with diarrhoea from Kolkata, Dibrugarh and Bhubaneswar in Eastern
      India, and Chandigarh, a city in Northern India. All the samples were genotyped
      for VP7 (G-type) and VP4 (P-type) gene by reverse transcription (RT) and
      multiplex PCR using different type specific primers. The strains with G1P[8]
      (32.5%) was predominant as reported earlier [Das et al. (2002) J Clin Microbiol
      40:146-149] followed by G2P[4](4.7%) and only one sample was of G4P[8]
      specificity. Along with these common types some rare strains like G1P[6], G2P[8],
      G2P[6], G4P[4], and G4P[6] were also detected in 14.3% of cases. Thirty percent
      of samples in this study were mixed infections and 21 (16.7%) specimens remained
      untypeable either for the VP7 or for the VP4 gene. After sequencing of the VP7
      gene, two G9 strains (RMC321 and ISO-3) were identified with P[8] and P[19]
      specificities. Sequence analysis revealed that they have much lower homology to
      the G9 strains (116E, INL1, and G16) isolated earlier from Indian subcontinent,
      but have much higher homology to isolates from Argentina, Brazil, Malawi, Taiwan,
      and USA suggesting a separate progenitor for these strains.

PMID- 14635026
TI  - Thymidine analogue reverse transcriptase inhibitors resistance mutations profiles
      and association to other nucleoside reverse transcriptase inhibitors resistance
      mutations observed in the context of virological failure.
AB  - During ZDV or d4T exposure, mutations at codons 41, 67, 70, 210, 215, and 219 can
      be selected and were named thymidine analogue mutations (TAMs). Some previous
      results suggested that different TAMs patterns could exist and that the kind of
      TAMs pattern could influence the virological response to some nucleoside reverse
      transcriptase inhibitors (NRTIs). In order to get more data about the relative
      prevalence of these patterns, their associations with other NRTI resistance
      mutations and the identification of the different stages observed during the
      acquisition of TAMs under treatment by NRTIs, we collected 1,098 RT sequences
      harbouring at least one TAM from patients failing to antiretroviral regimen.
      Sequences were stored in a database designed specifically to allow the retrieval
      of sequences that met specific criteria such as the occurrence and frequency of a
      particular mutation, the nature and frequency of the amino acid substitution at a
      given codon, and/or the rate of association between resistance mutations. Two
      pathways of TAMs can be identified: profile #1 (T215Y mutation linked) and
      profile # 2 (T215F mutation linked). The frequency of selection of profile # 1 is
      two times higher than profile # 2. The E44D/A + V118I complex, 69 insertions, and
      L74V mutation are associated to profile #1, whereas the Q151M complex and M184V
      mutation are associated to both profiles. As some NRTI resistance mutations were
      associated preferentially with profile #1, further studies are needed to explore
      if, the weaker efficacy observed on viruses harbouring this profile using some
      NRTIs, could be explained by the TAMs profile itself or the other associated NRTI
      resistance mutations.

PMID- 14635027
TI  - Distribution of TT virus genomic groups 1-5 in Brazilian blood donors, HBV
      carriers, and HIV-1-infected patients.
AB  - Human isolates of the highly prevalent TT virus (TTV) have been classified into
      five major genomic groups (1-5). The geographical distribution of the groups
      throughout the world is not well known. Five different PCR assays were developed
      in an attempt to amplify specifically TTV DNAs of each genomic group. Serum
      samples collected from 72 Brazilian adults (24 voluntary blood donors, 24
      hepatitis B virus (HBV) carriers, and 24 human immunodeficiency virus type 1 (HIV
      1)-infected patients) were tested. TTV DNA from at least one genomic group was
      detected in 11 (46%) blood donors, 13 (54%) HBV carriers, and 24 (100%) HIV-1
      patients. All five genomic groups were detected in the three populations, with
      the exception of group 2 in blood donors. Some samples, negative with all five
      specific assays, were positive with the commonly used untranslated region (UTR)
      PCR system. On the other hand, TTV DNA was detected in some samples by using
      specific assays but not with the UTR PCR. Mixed infections with 2-5 TTV isolates
      from different groups were detected in 21% blood donors, 29% HBV carriers, and
      71% HIV-1 patients. Fifteen PCR products (three obtained with each assay) were
      sequenced. Most sequences showed high (>86%) homology with those of TTV isolates
      belonging to their presumed groups. However, three sequences had low homology
      with all TTV sequences available from the DNA databanks. In conclusion, TTV
      isolates belonging to all five known genomic groups circulate in Brazil, and the
      results suggest the existence of new and as yet uncharacterised major genomic
      groups.

PMID- 14635028
TI  - Stress-induced subclinical reactivation of varicella zoster virus in astronauts.
AB  - Varicella zoster virus (VZV) becomes latent in human ganglia after primary
      infection. VZV reactivation occurs primarily in elderly individuals, organ
      transplant recipients, and patients with cancer and AIDS, correlating with a
      specific decline in cell-mediated immunity to the virus. VZV can also reactivate
      after surgical stress. The unexpected occurrence of thoracic zoster 2 days before
      space flight in a 47-year-old healthy astronaut from a pool of 81 physically fit
      astronauts prompted our search for VZV reactivation during times of stress to
      determine whether VZV can also reactivate after non-surgical stress. We examined
      total DNA extracted from 312 saliva samples of eight astronauts before, during,
      and after space flight for VZV DNA by polymerase chain reaction: 112 samples were
      obtained 234-265 days before flight, 84 samples on days 2 through 13 of space
      flight, and 116 samples on days 1 through 15 after flight. Before space flight,
      only one of the 112 saliva samples from a single astronaut was positive for VZV
      DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples
      were positive in all eight astronauts. No VZV DNA was detected in any of 88
      saliva samples from 10 healthy control subjects. These results indicate that VZV
      can reactivate subclinically in healthy individuals after non-surgical stress.

PMID- 14635030
TI  - Mini-review CD4 T cells are required for CD8 T cell memory generation.
AB  - Whereas the role of CD4 T cells in B cell memory generation is well established
      and unequivocal, the role that CD4 T cells play in CD8 responses was until
      recently far more elusive and controversial. A series of recent reports, however,
      have re-assessed the role of CD4 help on CD8 responses and have given rise to
      surprisingly unambiguous conclusions. While studying very different systems, they
      demonstrated that CD4 T cells are absolutely required for the generation of bona
      fide CD8 memory cells; the reports allow, for the first time, strong analogies to
      be made between B and CD8 memory cell generation. These data invite us to
      drastically change our idea of CD4 help on CD8 responses because they show that
      the old dichotomy - Th-dependent versus Th-independent CD8 responses - is no
      longer accurate.

PMID- 14635031
TI  - Generation and characterization of the humoral immune response to DNA
      immunization with a chimeric beta-amyloid-interleukin-4 minigene.
AB  - Active immunization with fibrillar beta-amyloid peptide (Abeta(42)) as well as
      passive transfer of anti-Abeta antibodies significantly reduces Abeta plaque
      deposition, neuritic dystrophy, and astrogliosis in the brain of mutant amyloid
      precursor protein (APP)-transgenic mice. Although the mechanism(s) of clearance
      of Abeta from the brain following active or passive immunization remains to be
      determined, it is clear that anti-Abeta antibodies are critical for clearance.
      DNA immunization provides an attractive alternative to direct peptide and
      adjuvant approaches for inducing a humoral response to Abeta. We constructed a
      DNA minigene with Abeta fused to mouse interleukin-4 (pAbeta(42)-IL-4) as a
      molecular adjuvant to generate anti-Abeta antibodies and enhance the Th2-type of
      immune responses. Gene gun immunizations induced primarily IgG1 and IgG2b anti
      Abeta antibodies. Fine epitope analysis with overlapping peptides of the
      Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The
      DNA minigene-induced anti-Abeta antibodies bound to Abeta plaques in brain tissue
      from an Alzheimer's disease patient demonstrating functional activity of the
      antibodies and the potential for therapeutic efficacy.

PMID- 14635032
TI  - O-Linked glycans control glycoprotein processing by antigen-presenting cells: a
      biochemical approach to the molecular aspects of MUC1 processing by dendritic
      cells.
AB  - MUC1 is a glycoprotein overexpressed in breast cancer and other adenocarcinomas,
      and is known to elicit cellular and humoral immunity directed against
      unglycosylated peptide epitopes in the repeat domain. Based on immunological
      evidence that O-linked glycans on repeat peptides remain intact during processing
      by dendritic cells (DC), we used MUC1 as a model to address the question which
      role O-linked glycans play in this process. We were able to identify the sites of
      proteolysis in MUC1 repeats and the enzyme(s) involved, and elucidated the site
      specific effects of O-glycosylation on MUC1 processing by human and mouse DC.
      Peptides generated by the cellular processing machinery from native mucin or
      (glyco)peptides suggest specific cleavage at Gly13-Ser14, His20-Gly1 and Thr3
      Ser4 peptide bonds in the tandem repeat GVTSAPDTRPAPGSTAPPAH resulting in the
      initial formation of STA27 or GVT20 and SAP17 as the final product with intact O
      glycosylation. Human cathepsin L and the corresponding mouse enzyme in low
      density endosomes were identified in vitro to catalyze this site-specific MUC1
      proteolysis. O-Glycosylation controls the processing by preventing proteolysis of
      the Thr3-Ser4 peptide bond if either amino acid is glycosylated, and is
      responsible for the inertness of tumor-associated MUC1 glycoforms to effective DC
      processing by masking this cleavage site.

PMID- 14635033
TI  - Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes
      in NOD mice.
AB  - Activation of an islet-specific immune response is an early yet essential step in
      autoimmune diabetes. The immune cells and antigen(s) involved in this early step
      and its anatomical site remain incompletely understood. To directly evaluate the
      site where islet-specific and diabetogenic lymphocytes are activated, we isolated
      lymphocytes from spleen and from pancreas-draining, gut-associated and
      subcutaneous lymph nodes of diabetic NOD mice and of young NOD mice, and
      transferred these into NOD scid/scid recipients devoid of endogenous islet
      specific immune responses themselves. Although spleen lymphocytes from diabetic
      NOD mice induced diabetes more rapidly than lymphocytes from any other lymphoid
      tissue, spleen lymphocytes from young NOD donors were not superior to other
      lymphocytes from the same donors. At a donor-age of 6 weeks, the most
      diabetogenic lymphocytes were found in pancreas-draining lymph node whereas gut
      associated lymph nodes and the spleen were sources of intermediate diabetogenic
      activity. Lymphocytes from peripheral lymph nodes were only weakly diabetogenic
      at this age, and also remained the least efficient later. Surprisingly,
      lymphocytes isolated even from 3-week-old NOD mice had diabetogenic potential.
      However, such cells were almost exclusively found in gut-associated lymph nodes.
      This suggests that initial priming of diabetogenic cells takes place in the gut
      whereas pancreas-draining lymph nodes may serve as the site of amplification of
      the autoimmune response.

PMID- 14635034
TI  - OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic
      colitis induced by dextran sulfate sodium in mice.
AB  - Interactions between APC and T lymphocytes have been implicated as a major factor
      contributing to inflammatory bowel disease. To test whether OX40/OX40L
      interaction plays a role in chronic intestinal inflammation, we induced chronic
      colitis using dextran sulfate sodium and treated the mice with a murine fusion
      protein (OX40-IgG). Treatment resulted in a dose-dependent and significant
      reduction of intestinal inflammation (46%) as measured by a histologic score. IL
      10 and IL-5 production from mesenteric lymph node cells increased 20-fold and 18
      fold, respectively. In colonic tissue, IL-10 mRNA levels increased and the
      expression of T-bet was decreased to 30%. IL-10 neutralization partly inhibited
      the beneficial effects of OX40-IgG treatment. Surprisingly, despite the reduction
      of inflammation we found the number and size of colonic lymphoid follicles
      increased, with an accumulation of CD4(+) cells in the mantle area. In contrast,
      the number of CD4(+) cells infiltrating the mucosa was significantly reduced, as
      was their CXCR5 expression (24-fold). We conclude that OX40/OX40L interaction
      contributes to the perpetuation of chronic colitis partly by suppressing IL-10
      production. Furthermore, our data suggest that the OX40/OX40L-induced CXCR5
      expression on CD4(+) cells may be important for the inflammatory process by
      allowing migration to the germinal center for further differentiation of CD4(+)
      cells before they infiltrate the chronically inflamed mucosa.

PMID- 14635035
TI  - Cutaneous lymphocyte antigen expression on human effector B cells depends on the
      site and on the nature of antigen encounter.
AB  - In contrast to T cells, information on skin-homing B cells expressing the
      cutaneous lymphocyte antigen (CLA) is sparse. CLA expression on human B cells was
      investigated among circulating immunoglobulin-secreting cells (ISC) and among
      antigen-specific antibody-secreting cells (ASC) elicited by parenteral, oral or
      rectal primary immunization, or by parenteral or oral secondary immunization with
      Salmonella typhi Ty21a. CLA expression was examined by combining cell sorting
      with an enzyme-linked immunospot assay. Among all ISC, the proportion of CLA(+)
      cells was 13-21%. Parenteral immunization induced antigen-specific ASC of which
      13% were CLA(+), while oral and rectal immunizations were followed by only 1% of
      CLA(+) ASC (p<0.001). Oral re-immunization was followed by an up-regulation of
      CLA (34-48%) regardless of the route of priming. Parenteral re-immunization
      elicited ASC of which 9-14% were CLA(+). In conclusion, the expression of CLA on
      human effector B cells depends on the site of antigen encounter: intestinal
      stimulation elicits cells with no CLA, while parenteral encounter elicits
      significant numbers of CLA(+) cells. Even though primary antigen encounter in the
      intestine failed to stimulate CLA expression, up-regulation of CLA was found upon
      intestinal antigen re-encounter. These findings may be of relevance in the
      pathogenesis of some cutaneous disorders.

PMID- 14635036
TI  - Granzyme B leakage-induced cell death: a new type of activation-induced natural
      killer cell death.
AB  - Activation-induced natural killer (NK) cell death is very rapid compared to
      activation-induced T or B cell death. Here we show that NK cell activation is
      accompanied by the leakage of granzymeB from intracellular granules into the
      cytoplasm. Evidence for granzyme B leakage includes the formation of granzyme
      B/serine proteinase inhibitor 9 (PI-9) complexes that are detected by
      immunoprecipitation as well as colocalization of granzyme B and PI-9 detected by
      immunocytochemistry. The pro-apoptotic molecule Bid, a specific substrate for
      granzyme B, was cleaved within 2 min following CD2-induced NK cell activation,
      suggesting that granzyme B triggers apoptosis by directing Bid to mitochondrial
      membranes. The granzyme B/PI-9 protein ratio was found to mirror the percentage
      of CD2-induced NK cell death, suggesting that an excess of leaked granzyme B over
      its inhibitor is a major determinant of cell death. We suggest that granzyme B
      leakage-induced cell death is an important determinant of activation-induced NK
      cell death and that this process may be important for the fate of NK cells which
      encounter malignant or virus-infected cells.

PMID- 14635037
TI  - CD8+ T cell-mediated suppression of intracellular Mycobacterium tuberculosis
      growth in activated human macrophages.
AB  - Animal models of tuberculosis point to a protective role for MHC class I
      restricted CD8(+) T cells, yet it is unclear how these cells protect or whether
      such findings extend to humans. Here we report that macrophages infected with
      Mycobacterium tuberculosis, rapidly process and present an early secreted
      antigenic target (ESAT-6)-specific HLA class I-restricted CD8(+) T cell epitope.
      When cocultured with CD8(+) T cells restricted through classical HLA class I
      molecules the growth of bacilli within macrophages is significantly impaired
      after 7 days. This slow antimycobacterial activity did not correlate with
      macrophage lysis but required cell contact. We also found that inhibitors of
      apoptosis either had no effect or augmented the CD8-mediated suppressive
      activity, suggesting that an activation signal might be involved. Indeed we show
      that CD8(+) T cells were able to activate macrophages through receptors that
      include CD95 (Fas). Consistent with these findings the CD8-mediated suppression
      of mycobacterial growth was partially reversed by Fas blockade. These data
      identify a previously unrecognized CD8(+) T cell-mediated mechanism used to
      control an intracellular infection of macrophages.

PMID- 14635038
TI  - Bet v 1, the major birch pollen allergen, initiates sensitization to Api g 1, the
      major allergen in celery: evidence at the T cell level.
AB  - Due to IgE cross-reactivity, birch pollen-allergic individuals frequently develop
      type I hypersensitivity reactions to celery tuber. We evaluated the T cell
      response to the major allergen in celeriac, Api g 1, and the cellular cross
      reactivity with its homologous major allergen in birch pollen, Bet v 1. Api g 1
      specific T cell lines (TCL) and clones (TCC) were established from peripheral
      blood mononuclear cells of allergic patients. Epitope mapping of Api g 1 with
      overlapping Api g 1-derived peptides revealed one dominant T cell-activating
      region, Api g 1(109-126). TCL and TCC generated with Api g 1 cross-reacted with
      the birch pollen allergen and, although initially stimulated with the food
      allergen, cellular responses to Bet v 1 were stronger than to Api g 1. Epitope
      mapping with Bet v 1-derived peptides revealed that T cells specific for several
      distinct epitopes distributed over the complete Bet v 1 molecule could be
      activated by Api g 1. Bet v 1(109-126) was identified as the most important T
      cell epitope for cross-reactivity with Api g 1. This epitope shares 72% amino
      acid sequence similarity with the major T cell-activating region of the food
      allergen, Api g 1(109-126). Our data provide evidence that humoral as well as
      cellular reactivity to the major celery allergen is predominantly based on cross
      reactivity with the major birch pollen allergen. The activation of Bet v 1
      specific Th2 cells by Api g 1, in particular outside the pollen season, may have
      consequences for birch pollen-allergic individuals.

PMID- 14635039
TI  - Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the
      binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes.
AB  - The C3b-binding receptor, CR1/CD35, supports CR2/CD21-mediated activation of
      complement by human B lymphocytes, possibly by associating with CR2 to promote or
      stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP
      convertase, C3i-Bb. To evaluate this hypothesis, we examined the uptake kinetics
      and binding equilibria for C3i dimer interaction with human blood cells in the
      absence and presence of CR1- and CR2-blocking mAb. C3i displayed dual uptake
      kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding
      to CR2. The forward rate constants (k(1)) for CR1 and CR2, operating
      independently, differed ca. 9-fold (k(1)=193+/-9.4 and 22.2+/-6.0 x 10(3) M(-1)s(
      1), respectively). Equilibrium binding of C3i to B lymphocytes was also complex,
      varying in strength by ca. 13-fold over the C3i concentration range examined. The
      maximum association constant (K(a, max)=109+/-27.2 x 10(7) l/mole) was ca. 9- and
      6-fold greater, respectively, than those for CR1 or CR2 acting alone (K(a)=13.2+/
      5.3 and 18.5+/-3.5 x 10(7) l/mole). The high avidity of the CR1-CR2 complex for
      C3i is consistent with its rates of C3i uptake and release being determined by
      CR1 and CR2, respectively.

PMID- 14635040
TI  - Critical role of Valpha14+ natural killer T cells in the innate phase of host
      protection against Streptococcus pneumoniae infection.
AB  - The present study was designed to elucidate the role of Valpha14(+) NKT cells in
      the host defense against pulmonary infection with Streptococcus pneumoniae using
      Jalpha281 gene-disrupted mice (Jalpha281KO mice) that lacked this lymphocyte
      subset. In these mice, pneumococcal infection was severely exacerbated, as shown
      by the shorter survival time and marked increase of live bacteria in the lung
      compared to wild-type (WT) mice. The proportion of Valpha14(+) NKT cells,
      detected by an alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramer,
      increased in thelung after S. pneumoniae infection. This increase was
      significantly reduced in mice with a genetic disruption of monocyte chemotactic
      protein (MCP)-1, which was produced in the early phaseof infection in WT mice. In
      the lungs of Jalpha281KO mice, the number of neutrophils was significantly lower
      at 12 h than that in WT mice. In support of this finding, macrophage inflammatory
      protein (MIP)-2 and TNF-alpha synthesis in infected lungs was significantly
      reduced at 3 h and at both 3 and 6 h, respectively, in Jalpha281KO mice, compared
      to WT mice. In addition, treatment of mice with alpha-GalCer significantly
      improved the outcome of this infection. Our results demonstrated MCP-1-dependent
      recruitment of Valpha14(+) NKT cells and their critical role in early host
      protection against S. pneumoniae by promoting the trafficking of neutrophils to
      the site of infection.

PMID- 14635041
TI  - Efficient generation and expansion of antigen-specific CD4+ T cells by
      recombinant influenza viruses.
AB  - Adoptive transfer of in vitro generated antigen-specific T cells has been
      successfully used to treat viral infections in immunodeficient patients.
      Therefore, methods for the rapid in vitro expansion of antigen-specific T cells
      are needed. Influenza virus efficiently infects dendritic cells, and peptides
      derived from viral proteins are processed and presented to CD8(+) cytotoxic T
      cells. However, both, CD4(+) and CD8(+) T cells are necessary for the efficient
      control of viral infections, and it is becoming increasingly clear that a T
      helper cell response is very important for the maintenance and strength of the
      immune response. Here we show that recombinant influenza virus efficiently
      infects a wide range of professional antigen-presenting cells and does not
      interfere with antigen presentation pathways. Using T cell clones for three
      different MHC class II-restricted antigens we demonstrate that peptides derived
      from these antigens are efficiently presented on MHC class II molecules.
      Importantly, it was possible to generate and expand antigen-specific CD4(+) T
      cells following in vitro infection of professional antigen-presenting cells with
      recombinant influenza virus. These findings support the notion that recombinant
      influenza virus is a valuable tool for the expansion of antigen-specific CD4(+) T
      cells in vitro.

PMID- 14635042
TI  - Breaking tolerance in hepatitis B surface antigen (HBsAg) transgenic mice by
      vaccination with cross-reactive, natural HBsAg variants.
AB  - Processing exogenous hepatitis B surface antigen (HBsAg) of the hepatitis B virus
      (HBV) generates the K(b)-binding S(208-215) epitope 1; processing endogenous
      HBsAg generates the K(b)-binding S(190-197) epitope 2. Cross-reactive CD8(+) T
      cell responses were primed to epitope 1 but not epitope 2 when mice were
      immunized with natural HBsAg(ayw), or HBsAg(adw2) variants differing within both
      epitopes by one or two residues. Expression of HBsAg(ayw) from a transgene in the
      liver renders (HBs-tg) mice tolerant to epitope 1 of HBsAg(ayw). CD8(+) T cells
      specific for epitope 1 could be primed in HBs-tg mice by HBsAg(adw2); these
      specific CD8(+) T cells cross-reacted with epitope 1 processed from the transgene
      encoded HBsAg(ayw). The liver of vaccinated HBsAg(ayw) transgenic mice showed
      severe histopathology and contained functional (IFNgamma-producing), cross
      reactive CD8(+) T cells, and vaccinated HBs-tg mice showed reduced antigenemia.
      Hence, vaccination with natural HBsAg variants from different HBV sero/genotypes
      can prime cross-reactive, specific CD8(+) T cell immunity that breaks tolerance
      to HBsAg.

PMID- 14635043
TI  - Thymic selection does not limit the individual MHC diversity.
AB  - The number of different major histocompatibility (MHC) molecules expressed per
      individual is widely believed to represent a trade-off between maximizing the
      detection of foreign antigens, and minimizing the loss of T cell clones due to
      self-tolerance induction. Using a mathematical model we here show that this
      argument fails to explain why individuals typically express of the order of 1020
      different MHC molecules. Expression of extra MHC types decreases the number of
      clones surviving negative selection, but increases the number of positively
      selected clones. Based on experimental parameter estimates, we show that the
      number of clones in the functional T cell repertoire would in fact increase if
      the MHC diversity within an individual were to exceed its normal value, until
      more than one hundred different MHC molecules would be expressed. Since
      additional MHC types also increase the number of presented pathogen peptides,
      resistance against pathogens only decreases at unrealistically high MHC
      diversities exceeding 1,500 different MHC molecules per individual.

PMID- 14635044
TI  - Regulation of peptide presentation by major histocompatibility complex class II
      molecules at the surface of macrophages.
AB  - We studied major histocompatibility complex class II-dependent presentation of
      two T cell epitopes delivered as synthetic peptides by fixed macrophages.
      Treatment of bone marrow macrophages with inhibitors of proteinases of the
      metallo-, aspartic and serine proteinase families enhanced presentation of
      peptides, indicating that several enzyme families participate in destructive
      antigen processing of exogenous peptides. High performance liquid chromatography
      and mass spectrometry analysis demonstrated the presence of peptide fragments in
      macrophage supernatants, and permitted identification of the cleavage sites which
      confirmed the enzyme families involved. Peptide fragments were shown to be
      competitive inhibitors of presentation of the full-length peptide to CD4 T cells
      by fixed and live macrophages. The results indicate that several classes of
      proteinases can modulate antigen presentation by at least two mechanisms: (1)
      degradation of extracellular oligopeptides and (2) generation of natural peptide
      ligands that block antigen presentation to CD4 T cells. The generation of
      inhibitory natural peptide ligands is a new mechanism of immunoregulation which
      could operate during the induction of T cell responses in a variety of
      situations.

PMID- 14635045
TI  - CD59 is physically and functionally associated with natural cytotoxicity
      receptors and activates human NK cell-mediated cytotoxicity.
AB  - Triggering of cytotoxicity in human NK cells is induced by the combined
      engagement of several triggering receptors. These include primary receptors such
      as NKG2D and the natural cytotoxicity receptors (NCR) NKp30, NKp46 and NKp44,
      while other molecules, including 2B4, NTB-A and NKp80, function as co-receptors.
      As reported in the present study, during an attempt to identify novel NK
      receptors or co-receptors, we found that CD59 functions as a co-receptor in human
      NK cell activation; engagement of CD59 by specific mAb delivers triggering
      signals to human NK cells, resulting in enhancement of cytotoxicity. Similar to
      other NK co-receptors, the triggering function of CD59, a
      glycosylphosphatidylinositol (GPI)-linked protein, depends on the simultaneous
      engagement of primary receptors such as NCR. Accordingly, CD59-dependent
      triggering was virtually restricted to NK cells expressing high surface densities
      of NKp46, and mAb-mediated modulation of NKp46 resulted in markedly decreased
      responses to anti-CD59 mAb. Biochemical analysis revealed that CD59 is physically
      associated with NKp46 and NKp30. Moreover, engagement of CD59 resulted in
      tyrosine phosphorylation of CD3zeta chains associated with these NCR, but not
      those associated with CD16. Thus, CD59-mediated costimulation of NK cells
      requires direct physical interaction of this GPI-linked protein with primary
      triggering NK receptors.

PMID- 14635046
TI  - Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate
      IL-4Ralpha-independent airway hyperreactivity.
AB  - The pathogenesis of human asthma and the development of key features of pulmonary
      allergy in mouse models has been critically linked to IL-13. Analyses of the
      receptor components employed by IL-13 have shown that delivery of this cytokine
      to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to
      induce disease, suggesting that this membrane protein is critical for transducing
      IL-13-mediated responses. The current study demonstrates that, in contrast to
      naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue
      eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these
      responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore,
      antigen stimulation induces an IL-13-regulated response that is independent of IL
      4Ralpha. To determine the role of IL-5 and eosinophils in the development of
      disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined
      in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly
      defective in their ability to produce IL-13 and failed to develop AHR, suggesting
      that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13
      dependent mechanism. Collectively, these results demonstrate that IL-13-dependent
      processes regulating the development of AHR and T helper bias persist in the in
      the lungs of allergic IL-4Ralpha(-/-) mice.

PMID- 14635047
TI  - p300 cooperates with Smad3/4 and Runx3 in TGFbeta1-induced IgA isotype
      expression.
AB  - We have shown previously that Smad3 and Smad4 mediate TGF-beta1-induced IgA
      expression. In the present study, we examined the involvement of Runx3 in this
      process. Overexpression of Runx3 in mice increased germ-line alpha (GLalpha)
      transcription, and transcription was further augmented when B lymphoma and LPS
      activated murine spleen cells were co-transfected with Smad3/4. Overexpression of
      Runx3 and Smad3/4 increased IgA secretion by both cell types in response to TGF
      beta1. p300, which has histone acetyltransferase activity, further augmented TGF
      beta1-induced GLalpha transcription promoted by Smad3/4 and Runx3. These
      observations were confirmed by examining the influence of Smad3/4, Runx3 and p300
      on the expression of endogenous GLalpha and post-switch alpha transcripts.E1A, an
      inhibitor of p300, blocked both GLalpha promoter activity and the enhancement of
      endogenous GLalpha transcription by Smad3/4 and Runx3. We conclude that p300
      cooperates with Smad3/4 and Runx3 in stimulating TGF-beta1-induced GLalpha
      transcription and subsequent IgA isotype expression, while E1A inhibits these
      cooperative effects.

PMID- 14635048
TI  - IL-12 receptor deficiency revisited: IL-23-mediated signaling is also impaired in
      human genetic IL-12 receptor beta1 deficiency.
AB  - IFN-gamma and IL-12 are crucial cytokines for cell-mediated immunity against
      intracellular pathogens. We have previously shown that human IL-12Rbeta1
      deficiency leads to impaired IL-12 responsiveness and unusual susceptibility to
      infections due to mycobacteria and salmonellae. IL-23 is a cytokine with
      functions that partially overlap with those of IL-12. IL-23 consists of IL-12p40
      and a novel p19 protein, and binds to a receptor complex comprising IL-12Rbeta1
      and IL-23R. Thus, IL-12Rbeta1-deficiency may impair both IL-12- and IL-23
      signaling, and both may contribute to the immunological phenotypes. To examine
      whether IL-12Rbeta1 is essential for IL-23 signaling in human T cells, we have
      studied IL-23 responsiveness of four IL-12Rbeta1-deficient individuals. Whereas
      IL-23 promoted IFN-gamma production by CD4(+) and CD8(+) T cells in controls, IL
      12Rbeta1-deficient T cells lacked IL-23-induced IFN-gamma secretion, but
      responded normally to IL-2, IL-4, IL-15 and IL-18. We also show that induction of
      IFN-gamma production by IL-23 depends upon TCR-ligation and is enhanced by CD28
      costimulation. Furthermore, IL-23 cooperates with IL-12 and IL-18 in promoting
      IFN-gamma production in controls, but not in patients. We conclude that IL
      12Rbeta1-deficiency impairs IL-12- and IL-23-dependent signaling in human T
      cells. The syndrome caused by IL-12Rbeta1-deficiency thus needs to be
      reinterpreted as resulting from defective IL-12-as well as IL-23-mediated
      immunity.

PMID- 14635049
TI  - A phenotypically distinct subset of immature B cells exhibits partial activation,
      increased survival, and preferential expression of VhS107.
AB  - We have observed that immature B cells (IgM(low)IgD(-)) in the bone marrow of
      adult BALB/c mice exhibit heterogeneity, with a distinct subpopulation (
      approximately 4-10%) expressing the CD43/S7 surface protein. These CD43/S7(+)
      immature B cells often express other surface antigens associated with B cell
      activation (CD5, CD11b, PD-1). Generation of optimal numbers of CD43/S7(+)
      immature B cells requires expression of a functional Btk protein, consistent with
      activation as a requisite for the CD43/S7(+) immature B cell phenotype. Like
      typical CD43/S7(-) immature B cells, the CD43/S7(+) immature B cells are
      predominantly resting cells, which are derived from cycling bone marrow B cell
      precursors. The CD43/S7(+) immature B cell population exhibits enhanced survival
      in vivo upon administration of the apoptosis-inducing corticosteroid,
      dexamethasone. Finally, CD43/S7(+) immature B cells show a fourfold increase in
      incidence of VhS107 micro heavy chain expression compared to the CD43/S7(-)
      immature B cells. Therefore, in adult murine bone marrow, the presence of a
      phenotypically distinct immature B cell population can be demonstrated which has
      undergone partial activation leading to increased survival and BCR-dependent Vh
      repertoire selection.

PMID- 14635050
TI  - Differential role of IL-18 and IL-12 in the host defense against disseminated
      Candida albicans infection.
AB  - IFN-gamma plays a crucial role in the defense against infection with Candida
      albicans. Since IL-18 and IL-12 are strong stimuli of IFN-gamma production, we
      investigated whether endogenous IL-18 and IL-12 are involved in the host defense
      during disseminated candidiasis. IL-18 knockout (IL-18-/-) mice, but not IL-12-/-
      mice, displayed an increased mortality due to C. albicans infection, accompanied
      by a decreased clearance of the yeasts from the kidneys late during the course of
      infection. Histopathology of the organs, combined with phagocyte recruitment
      experiments, showed a decreased influx of monocytes at the sites of Candida
      infection, mainly in the IL-18-/- mice. Whereas production of the chemokine KC
      was decreased in both IL-18-/- and IL-12-/- mice, MIP-2 production was deficient
      only in IL-18-/- animals, which may explain the differences in phagocyte
      recruitment. In addition, although IFN-gamma production capacity, as a parameter
      of the Th1-protective immunity, was reduced by 65 to 80% in the IL-12-/- mice,
      this defect was even more pronounced in the IL-18-/- mice (85 to 95% down
      modulation). In conclusion, the anticandidal effects of endogenous IL-18 are
      mediated late during the infection by assuring a proper IFN-gamma response and
      promoting the infiltration of the site of infection by monocytes.

PMID- 14635051
TI  - B cell defects in SLP65/BLNK-deficient mice can be partially corrected by the
      absence of CD22, an inhibitory coreceptor for BCR signaling.
AB  - CD22 is an inhibitory coreceptor for B cell receptor (BCR) signaling. The
      inhibition is most likely mediated by activation of SHP-1. We found that
      SLP65/BLNK reaches maximal tyrosine-phosphorylation at earlier time points in
      CD22(-/-) than in wild type B cells upon BCR cross-linking, suggesting that
      SLP65/BLNK is a substrate of SHP-1. However, in contrast to the defective Ca(2+)
      mobilization of SLP65/BLNK(-/-) B cells, there was a clear Ca(2+) response in
      SLP65/BLNKxCD22 double-deficient B cells. This implies that SLP65/BLNK is not the
      sole target of SHP-1 in the regulation of the Ca(2+) signaling strength. While
      SLP65(-/-) mice show several blocks of B cell differentiation, in SLP65/BLNK x
      CD22 double-deficient mice the maturation block of B cells in the spleen was
      partially rescued. However, the proliferative responses of B cells from both
      SLP65/BLNK(-/-) and double-deficient mice were defective after IgM- or CD40
      stimulation. These results show that SLP65/BLNK is not absolutely essential for
      Ca(2+) induction in B cells, because the deficiency of this adapter can be by
      passed by the additional deletion of an inhibitory receptor. Furthermore, these
      experiments suggest that B cell maturation in the spleen is directly dependent on
      the strength of BCR-derived Ca(2+) signals.

PMID- 14635052
TI  - Comparative analysis of NK- or NK-CTL-mediated lysis of immature or mature
      autologous dendritic cells.
AB  - Natural killer (NK) cells have been shown to kill efficiently autologous immature
      dendritic cells (iDC), while sparing those undergone maturation. In this study we
      investigated the effect of the interaction between autologous DC and NK-cytolytic
      T lymphocytes (NK-CTL), a subset of HLA-E-restricted CD8(+) T cells that express
      HLA class I-specific inhibitory NK receptors. Although these cells share with NK
      cells various phenotypic and functional features (such as the capacity to lyse
      most allogeneic, NK-susceptible tumor cell lines), different from NK cells, NK
      CTL failed to lyse autologous DC. However, after pulsing DC with a
      cytomegalovirus-derived, HLA-E-binding peptide recognized by NK-CTL, both iDC and
      mature DC became highly susceptible to lysis. On the other hand,the addition of
      the peptide resulted in the down-regulation of the NK-mediated lysis of the same
      autologous iDC. The capability of killing autologous DC, presenting a non-self,
      HLA-E-binding peptide, may represent a feedback mechanism by which NK-CTL down
      regulate HLA-E-restricted responses to certain pathogens.

PMID- 14635053
TI  - Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple
      sclerosis patients.
AB  - A longitudinal study of Ig V gene segments utilized by B cells from the
      cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS) was
      carried out using RT-PCR methodologies. One patient with a relapsing-remitting
      (RR)-MS was investigated at onset and at relapse, 1 year later. A patient with
      secondary-progressive (SP)-MS was tested 9 and 13 years after disease onset.
      Sequence analyses of V(H)DJ(H) segments bearing V(H)3 and V(H)4 that were
      obtained from Cgamma cDNA genes demonstrated a substantial proportion of shared
      clones in the samples taken at different times; these clones were identical or
      closely related, i.e. had the same third complementary determining region (CDR)
      of the H chain variable region gene (HCDR3) with different mutations in the V(H)
      segment. Collectively, these data demonstrate that in MS patients there is a
      strong selective pressure, which could be exerted by antigen (or autoantigen)
      stimulation, for the maintenance and partial diversification of certain V(H)DJ(H)
      Cgamma sequences.

PMID- 14635054
TI  - IL-21 induces both rapid maturation of human CD34+ cell precursors towards NK
      cells and acquisition of surface killer Ig-like receptors.
AB  - The NK cell maturation from CD34(+) Lin(-) hematopoietic cell precursors is a
      complex process that requires the direct contact with stromal cells and/or the
      synergistic effect of different cytokines. In this study we show that IL-21 is
      capable of inducing an accelerated NK cell maturation when added to cultures of
      CD34(+) Lin(-) cells isolated from human cord blood supplemented with IL-15, Flt3
      L and SCF. After 25 days of culture, 50% of CD56(+) cells expressed various NK
      cell markers including the NKp46 and NKp30 triggering receptors, the CD94/NKG2A
      inhibitory receptor and CD16. At day 35, substantial fractions of NK cells
      expressed KIR, CD8 and CD2, i.e. surface markers expressed by mature NK cells,
      that are virtually undetectable in developing NK cells cultured in the absence of
      IL-21. Remarkably, similar to mature NK cells all these markers were included in
      the CD56(dim) cell fraction, while the CD56(bright) population was only composed
      of CD94/NKG2A(-) and CD94/NKG2A(+) cells. Thus, IL-21 allows the induction of a
      full NK cell maturation in vitro and offers an important tool for dissecting the
      molecular mechanisms involved in different steps of NK cell maturation and in the
      acquisition of a mature KIR repertoire.

PMID- 14635055
TI  - Hepatitis C virus non-structural protein 4 suppresses Th1 responses by
      stimulating IL-10 production from monocytes.
AB  - The majority of hepatitis C virus (HCV) infections become chronic, despite the
      presence of HCV-specific cellular and humoral immune responses. We have
      previously suggested that IL-10-secreting antigen-specific regulatory T cells may
      contribute to viral persistence, and demonstrate here that peripheral blood
      mononuclear cells (PBMC) from chronically HCV-infected patients secrete IL-10,
      but not IFN-gamma, in response to HCV nonstructural protein 4 (NS4). A
      neutralizing anti-IL-10 antibody restored this defective antigen-specific IFN
      gamma production in vitro. Furthermore, PBMC from normal individuals secreted IL
      10 in response to NS4, suggesting that cells of the innate immune system, in
      addition to T cells, produced IL-10 in the HCV-infected patients. Cell separation
      experiments revealed that the innate IL-10 was produced by blood monocytes, but
      not dendritic cells (DC). In addition, NS4 inhibited IL-12 production by PBMC in
      response to LPS and IFN-gamma, and Th1 responses to recall antigens in normal
      individuals. Furthermore, supernatants from NS4-stimulated monocytes inhibited
      LPS-induced maturation of DC and suppressed their capacity to stimulate
      proliferation and IFN-gamma production by allospecific T cells. Our data suggest
      that HCV subverts cellular immunity by inducing IL-10 and inhibiting IL-12
      production by monocytes, which in turn inhibits the activation of DC that drive
      the differentiation of Th1 cells.

PMID- 14635056
TI  - Inflammatory pathogenesis of snake venom metalloproteinase-induced skin necrosis.
AB  - Local tissue damage, characterized by edema, hemorrhage and necrosis, is a common
      consequence of envenoming by many vipers. We have investigated the contribution
      of inflammatory responses induced by the venom metalloproteinase jararhagin
      (isolated from Bothrops jararaca venom) in the development of these lesions.
      Local venom effects (edema, hemorrhage and necrosis) were induced experimentally
      in knockout mice deficient in the TNF receptors TNFR1 or TNFR2, IL-1betaR, IL-6
      and iNOS. Jararhagin-induced dermal necrosis was abolished in mice deficient in
      the TNF receptors TNFR1 and TNFR2, and the same activity was significantly
      reduced in IL-6(-/-) mice. There was no significant difference in edema and
      hemorrhage activities following jararhagin insult between knockout and WT
      strains, indicating that these local venom metalloproteinase-induced effects are
      independent of these pro-inflammatory mediators. The contribution of both TNF
      receptors and IL-6 in local tissue necrosis raises important therapeutic issues
      regarding the treatment of local envenoming.

PMID- 14635057
TI  - Age-related defects in CD4+ T cell activation reversed by glycoprotein
      endopeptidase.
AB  - CD4(+) T cells from old mice show defects in the activation process including
      deficiency in the formation of immunosynapses with antigen-presenting cells. We
      show that CD4(+) T cells from old mice express unusually high levels of
      glycosylated forms of the bulky T cell glycoprotein CD43, particularly on a
      subset of functionally anergic cells expressing P-glycoprotein. T cells from old
      donors also show a decline in the association of CD43 with cytoskeletal matrix
      and in the proportion of T cells that can exclude CD43 from the synapse. O
      sialoglycoprotein endopeptidase, which removes the external domain of CD43 and
      other O-sialoglycoproteins from the aged naive CD4(+) T cells of TCR-transgenic
      mice, restores early agonist-independent stages and later agonist-dependent
      stages of synapse formation as well as expression of the activation markers CD69
      and CD25 to the levels found in the young mice. These data support a model in
      which O-glycosylated forms of T cell surface molecules, including CD43, are
      largely responsible for age-related defects in TCR signaling and function.

PMID- 14635058
TI  - Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell
      activation.
AB  - Amongst the many types of regulatory cells that have been described during the
      past few years, the spontaneously occurring population that is characterized by
      co-expression of CD4 and CD25 appears to play a key role in the prevention of
      autoimmunity and the maintenance of transplantation tolerance. In this study we
      have examined the ability of CD4(+)CD25(+) T cells to regulate human CD8(+) T
      cells, and the behavior of CD8(+) T cells following activation in the presence of
      regulatory CD4(+)CD25(+) T cells. The experiments described here demonstrate that
      human CD4(+)CD25(+) T cells cause pronounced and sustained inhibition of CD8(+) T
      cell proliferation in response to polyclonal and allogeneic stimulation. The
      regulation of CD8(+) T cell activation was cell contact-dependent and included
      inhibition of perforin, granzyme B and IFN-gamma cytokine production at the
      transcriptional level and impaired cytotoxicity. The regulated CD8(+) T cell
      population showed sustained hyporesponsiveness and refractoriness to exogenous IL
      2. These data provide insights into the short- and long-term effects of
      CD4(+)CD25(+) T cells on CD8(+) T cells that could be of considerable value in
      optimizing vaccination against tumor and viral antigens.

PMID- 14635059
TI  - Detection of antigen-specific T cells by cytokine flow cytometry: the use of
      whole blood may underestimate frequencies.
AB  - Antigen-specific T cells may be detected and enumerated by short-term ex vivo
      antigen-specific stimulation followed by cytokine flow cytometry. Most
      frequently, intracellular IFN-gamma is used to identify T cells specific for
      cytomegalovirus (CMV), Epstein-Barr virus or HIV. Some researchers use whole
      blood, others peripheral blood mononuclear cells (PBMC) in this assay; however,
      the performance of the two systems has never been directly compared. Blood was
      drawn from previously characterized healthy CMV-positive donors, and CMV-derived
      peptides or CMV lysate were used as stimulants. In an initial series of
      experiments, lithium-heparin was identified as the best coagulant to be used.
      Dose-response curves were established using concentrations between 0.1 and 40
      microg/ml of peptides and between 0.1 and 20 microg/ml of virus lysate,
      respectively. IFN-gamma-positive T cells were expressed as percent of the
      reference population, and frequencies measured in whole blood and PBMC were
      compared. Maximum responses were consistently higher in PBMC than in whole blood
      and were reached at lower concentrations of stimulant. In several instances,
      responses identified with PBMC were not at all detected with whole blood. In
      summary, studies using whole blood in this type of assay are likely to
      underestimate the frequencies of antigen-specific T cells.

PMID- 14635060
TI  - Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune
      responses.
AB  - The development and the differentiation of CD8(+) T cells are dependent on IL-15.
      Here, we have studied the source and mechanism of how IL-15 modulates CD8(+) T
      cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity
      (DTH) models. IL-15-deficient (IL-15(-/-)) mice or mice treated with soluble IL
      15Ralpha as an IL-15 antagonist showed significantly reduced CD8(+) T cell
      dependent DTH responses, while activation of CD4(+) T cell and B cell functions
      remained unaffected. Injection of antigen-labeled dendritic cells (DC) from IL
      15(+/+), IL-15(-/-) or IL-15Ralpha(-/-) mice revealed that DC-derived IL-15 is an
      absolute requirement for the initiation of DTH response. The re-establishment of
      the interaction of IL-15 with the IL-15Ralpha by incubating IL-15(-/-) DC with IL
      15 completely restored the capacity to prime T cells for DTH induction in vivo.
      Moreover, IL-15 also enhanced secretion of pro-inflammatory cytokines by DC and
      triggered in vitro CD8(+) T cell proliferation and IL-2 release. Taken together,
      the data suggest that an autocrine IL-15/IL-15Ralpha signaling loop in DC is
      essential for inducing CD8(+)-dependent Th1 immune responses in mice. Therefore,
      targeted manipulation of this loop promises to be an effective, novel strategy
      for therapeutic modulation of clinically relevant DTH reactions.

PMID- 14635061
TI  - Uncompromised generation of a specific H-2DM-dependent peptide-MHC class II
      complex from exogenous antigen in Leishmania mexicana-infected dendritic cells.
AB  - Leishmania infection inhibits the capacity of macrophages (MPhi) to present
      antigens to CD4(+) T cells. Relocation of MHC class II and H-2DM to the
      parasitophorous vacuole (PV) and their subsequent degradation by the parasite may
      contribute to this defect. Dendritic cells (DC) are critical for initiation of
      primary T cell responses. DC can process Leishmania antigen and elicit Leishmania
      specific T cells, but it is unknown whether exposure to Leishmania impairs this
      capacity. In particular, it is not clear whether DC containing live parasites
      efficiently process and present antigens. We investigated the ability of mouse
      bone marrow-derived DC infected with L. mexicana to generate pigeon cytochrome c
      (PCC) peptide-MHC class II complexes, using the mAb D4, which recognizes PCC(89
      104) H-2E(k), and the PCC-specific T cell hybridoma 2B4. We show that H-2DM
      dependent complex generation is not compromised by infection and that complexes
      are fully recognized by specific T cells. We further show that in contrast to
      infected MPhi, in infected DC cytoplasmic H-2DM is not down-regulated and not
      relocated to the parasite-containing vacuole. This observation may explain the
      continued ability of infected DC to present PCC, and also indicates differences
      in the habitat of these intracellular parasites in DC compared to MPhi.

PMID- 14635062
TI  - Contrasting roles of DAP10 and KARAP/DAP12 signaling adaptors in activation of
      the RBL-2H3 leukemic mast cell line.
AB  - A common feature of hematopoietic activating immunoreceptors resides in their
      association at the cell surface with transmembrane signaling adaptors. Several
      adaptors, such as the CD3 molecules, FcRgamma and KARAP/DAP12, harbor
      intracytoplasmic immunoreceptor tyrosine-based activation motifs (ITAM) that
      activate Syk-family protein tyrosine kinases. In contrast, another transmembrane
      adaptor, DAP10, bears a YxxM motif that delivers signals by activation of lipid
      kinase pathways. We show here that the human signal-regulatory protein SIRPbeta1
      can associate with both DAP10 and KARAP/DAP12 in a model of RBL-2H3 cell
      transfectants. In association with KARAP/DAP12, SIRPbeta1 complexes are capable
      of inducing serotonin release and tumor necrosis factor (TNF) secretion. By
      contrast,in the absence of KARAP/DAP12, engagement of SIRPbeta1:DAP10 complexes
      does not lead to detectable serotonin release or TNF secretion by RBL-2H3
      transfectants. However, triggering of SIRPbeta1:DAP10 complexes co-stimulates RBL
      2H3 effector function induced by sub-optimal stimulation of the endogenous
      FcepsilonRI complex. Therefore, we report here a cellular model in which the
      association of a cell surface receptor with various signaling adaptors dictates
      the co-stimulatory or the direct stimulatory properties of the complex.

PMID- 14635063
TI  - Clinicopathologic features of metastasis in nonsentinel lymph nodes of breast
      carcinoma patients.
AB  - BACKGROUND: In breast carcinoma patients with a positive sentinel lymph node
      (SN), the value of complete axillary lymph node dissection has been questioned.
      Multiple published reports have attempted to identify clinicopathologic
      characteristics of the primary tumor and SN that are associated with an increased
      likelihood of positive nonsentinel lymph nodes (NSN). Because of differences in
      lymph node evaluation techniques and limited patient numbers in each study, the
      authors performed a meta-analysis to assess the regularity and relative strength
      of association between various characteristics and the risk of NSN metastasis.
      METHODS: A MEDLINE search identified 15 candidate studies, 11 of which met the
      criteria for analysis. General elements of the studies, the pathologic
      characteristics evaluated, and the results for selected characteristics were
      compared. Original data were abstracted from each study and used to calculate
      odds ratios. The Mantel-Haenszel common odds ratios were calculated to determine
      the relative strength of the associations. RESULTS: Despite methodologic
      differences, the correlation between positive NSNs and certain pathologic
      characteristics was found to be remarkably similar among studies. The 5
      individual characteristics found to be associated with the highest likelihood of
      NSN metastasis are SN metastasis > 2 mm in size, extranodal extension in the SN,
      tumor size > 2 cm, > 1 positive SN, and lymphovascular invasion in the primary
      tumor. CONCLUSIONS: There is general concordance among studies regarding the
      association between pathologic characteristics and NSN metastasis in breast
      carcinoma patients with a positive SN. The pooled analysis identified those
      factors with the strongest associations that should be evaluated routinely in SN
      specimens and included in prospective databases for the development of a
      predictive model.

PMID- 14635064
TI  - Skin-sparing mastectomy. specialty bias and worldwide lack of consensus.
AB  - BACKGROUND: Skin-sparing mastectomy (SSM) is a variation of modified radical
      mastectomy (MRM) optimized for reconstruction. The authors attempted to determine
      SSM attitudes and biases within different specialties and countries throughout
      the world. METHODS: The authors polled 11,485 individuals via e-mail, including
      members of surgical, medical, and breast oncology societies, about SSM.
      Respondents were directed to a survey website where data were directly entered
      into a database. RESULTS: Among 1027 respondents, 19 said their knowledge was
      insufficient to attempt the survey. Surveys were completed by 1008 respondents
      (8.8%) from 52 countries, comprising 436 (43.3%) surgeons, 376 (37.3%) medical
      oncologists, 146 (14.5%) radiation oncologists, and 50 (5.0%) individuals from
      other fields. Of the respondents, 61.9% stated that SSMs are performed at their
      institution. However 19.1% of these believed that SSM leaves the nipple and
      areola intact. This perception was higher outside the U.S. (P < 0.0001). Despite
      knowledge by 77.8% that SSM does not have a higher local disease recurrence rate
      than MRM, 25.3% of these individuals did not believe the literature. This was
      most prevalent among radiation oncologists (48.5%), as was the belief that SSM is
      contraindicated in patients with ductal carcinoma in situ and invasive breast
      carcinoma (23.3%). CONCLUSIONS: Despite a developing body of literature, there
      was variation in opinion among specialties and a lack of understanding of SSM.
      Many physicians were not familiar with the literature. Among those who were,
      skepticism was highest among radiation oncologists. Although these results were
      indicative of only those responding, education about SSM is needed across
      specialties and in other countries if the procedure is to be widely accepted.

PMID- 14635065
TI  - Management of nonsinonasal neuroendocrine carcinomas of the head and neck.
AB  - BACKGROUND: Nonsinonasal neuroendocrine carcinomas (NSNEC) of the head and neck
      are rare and pose a diagnostic and management challenge. The authors undertook a
      retrospective study to gain insights into the spectrum of clinicopathologic
      characteristics, patterns of failure, and optimal management of patients with
      this disease. METHODS: The authors treated 23 adults with pathologically proven,
      nonmetastatic, primary NSNEC from 1984 to 2001. The majority (13 patients) had
      laryngeal origin with the following American Joint Committee on Cancer stage
      distribution: Stage I disease in 1 patient, Stage II disease in 2 patients, Stage
      III disease in 6 patients, and Stage IV disease in 14 patients. Nine patients
      underwent definitive surgery with or without postoperative radiation, and 14
      patients received definitive radiotherapy. The median definitive radiation dose
      was 66 grays (Gy) (range, 44-72 Gy) using conventional fractionation. Fourteen
      patients received chemotherapy, with two to four cycles of induction platinum
      plus etoposide used most commonly. RESULTS: The median follow-up time for
      surviving patients was 40 months (range, 15-89 months). The actuarial 2-year and
      5-year overall survival (OS) rates were 53% and 33%, respectively; and the
      disease-free survival (DFS) rates were 41% and 25%, respectively. Both the 2-year
      OS rate (68% vs. 30%; P = 0.002) and the 2-year DFS rate (55% vs. 17%; P = 0.004)
      were improved with chemotherapy compared with local therapy alone. Seventy-five
      percent of patients with measurable disease had complete clinical responses to
      induction chemotherapy. There was 100% complete clinical response of tumor after
      radiotherapy. The actuarial 2-year local failure rate was 23%. Chemotherapy did
      not reduce local failure (P = 0.91). There was no regional failure. The 2-year
      and 5-year distant metastasis rates were 54% and 71%, respectively. The 2-year
      rates of metastases without and with chemotherapy were 79% and 39%, respectively
      (P = 0.006). The 2-year and 5-year rates of intracranial metastases were 25% and
      44%, respectively, and the 2-year and 5-year rates of isolated brain metastases
      were 21% and 41%, respectively. CONCLUSIONS: Based on these results, the authors'
      treatment strategy for patients with NSNEC is sequential chemotherapy and
      radiation. They recommend full-dose radiotherapy alone for patients with NSNEC
      who achieve a complete clinical response to induction chemotherapy. Newer
      chemotherapeutic regimens or additional adjuvant chemotherapy should be
      investigated for patients with NSNEC given the high rate of distant failure. Due
      to the very high rate of brain metastases among patients in the current study,
      the authors now consider incorporating prophylactic cranial irradiation into
      primary radiotherapy for individual patients who have complete clinical responses
      to induction chemotherapy.

PMID- 14635066
TI  - Reassessment of the 1997 TNM classification system for renal cell carcinoma.
AB  - BACKGROUND: The 1997 TNM staging classification for renal cell carcinoma (RCC)
      defined Stage I tumors as organ-confined tumors measuring up to 7 cm in size. The
      authors evaluated the validity of this cutoff size by assessing the survival of
      patients with Stage I RCC according to a series of alternative size cutoff
      values. In addition, the authors determined how these size cutoffs affected the
      risk of having nonorgan-confined tumors, regional lymph node involvement, and
      metastatic disease. METHODS: A database containing the records of 1324 patients
      with RCC who underwent open radical nephrectomy between 1960 and 1991 was
      evaluated. Patients with Stage I disease were stratified by size cutoffs ranging
      from 2.5 to 7.0 cm in 0.5-cm increments. Five-year disease-specific survival
      (DSS) rates were estimated using the Kaplan-Meier method. The log-rank test was
      used to compare survival curves. The survival of patients with tumors smaller
      than a specified size cutoff was compared with the survival of patients with
      tumors larger than that cutoff and the most discriminating cutoff was identified.
      The same size cutoffs were used to compare the incidence of local nonorgan
      confined, lymph node-positive, and metastatic disease for all patients with
      tumors 7.0 cm or smaller. RESULTS: Of 544 evaluable patients, 351 patients had
      tumors 7.0 cm or smaller and 233 of these patients had 1997 Stage I (T1N0M0)
      disease. When patients with 1997 Stage I tumors were separated using the various
      size cutoffs, survivals were most different using a 5.0-cm cutoff. The 5-year DSS
      rates for patients with Stage I tumors 5 cm or smaller versus those with tumors
      measuring 5.1-7 cm were 94.6% versus 79.2% (P = 0.003). Furthermore, the survival
      of patients with Stage I RCC lesions measuring 5.1-7.0 cm was the same as for
      patients with 1997 Stage II (T2N0M0) RCC. The difference in probability of having
      local nonorgan-confined disease was also greatest with a 5.0 cm cutoff value.
      Nonorgan- confined disease was reported to be present in 16.2% of the patients
      with tumors smaller than 5.0 cm compared with 36.8% of the patients with tumors
      measuring 5.1-7.0 cm in size. The difference in the probabilities of having lymph
      node-positive or metastatic disease did not change significantly using any of the
      cutoffs, although the probability of both of these increased with increasing
      tumor size. CONCLUSIONS: Survival and disease recurrence analysis in a large
      group of patients with RCC who underwent radical nephrectomy showed that the 1997
      TNM cutoff of 7.0 cm used to separate Stage I from Stage II disease was too high.
      A size-related survival difference was found among patients with organ-confined
      1997 Stage I disease and a 5.0-cm cutoff best stratified this difference. This
      finding was in general agreement with the changes made in the 6th edition of the
      American Joint Committee on Cancer cancer staging manual. Patients with tumors
      measuring between 5.1 cm and 7.0 cm were found to have the same survival as
      patients with Stage II disease. Thus, subclassification of T1 into T1a and T1b,
      as in the 6th edition of the AJCC cancer staging manual, may not be optimal. The
      5-cm cutoff also best stratified the risk of developing nonorgan-confined
      disease. This finding may have an impact on nephron-sparing surgery in selected
      patients. The findings of the current study, as well as those of others,
      supported an upper size cutoff of 4-5 cm for patients with Stage I RCC.

PMID- 14635067
TI  - Disease-specific symptoms and general quality of life of patients with prostate
      carcinoma before and after primary three-dimensional conformal radiotherapy.
AB  - BACKGROUND: Approximately 189,000 men are diagnosed with prostate carcinoma each
      year and more than 1 million are living with the disease. Good prognoses and
      undesirable sequelae accompany each of several available primary and adjuvant
      treatment options. The current study explored the effects of primary three
      dimensional conformal radiotherapy with or without neoadjuvant hormonal therapy
      on urinary, bowel, and sexual symptoms and health-related quality of life
      (HRQOL). METHODS: A prospective, repeated-measures design study included 100
      patients. Data from the Medical Outcomes Study Short Form Health Survey (a
      measure of general HRQOL) and a 12-item symptom questionnaire were collected
      before the start of radiotherapy, approximately 1-3 months after completion of
      treatment, and again approximately 5-10 months after completion of treatment for
      follow-up. RESULTS: Patients reported few urinary symptoms after treatment. Bowel
      frequency and urgency were reported more frequently posttreatment and at follow
      up. Erectile difficulties, which were common pretreatment, were reported with
      increased frequency posttreatment and at follow-up. General HRQOL scores were
      higher than age-related general population norms for men at all three data
      collection times, but there were significant losses posttreatment for patients'
      physical functioning and vitality. At the 5-10-month follow-up, physical
      functioning remained lower but vitality scores regained some of the losses. A
      more extended follow-up is needed. Neoadjuvant therapy, which was received before
      the pretreatment data collection, had a deleterious effect on erectile
      functioning but no interactive effects with the radiotherapy on symptoms or
      HRQOL. CONCLUSIONS: Although patients with a diagnosis of prostate carcinoma
      experienced increased bowel and sexual dysfunction and decreased vitality after
      radiotherapy, their HRQOL scores remained at or above age-related general
      population norms.

PMID- 14635068
TI  - The percentage of prostate needle biopsy cores with carcinoma from the more
      involved side of the biopsy as a predictor of prostate specific antigen
      recurrence after radical prostatectomy: results from the Shared Equal Access
      Regional Cancer Hospital (SEARCH) database.
AB  - BACKGROUND: The authors previously found that, although the total percentage of
      prostate needle biopsy cores with carcinoma was a significant predictor of
      prostate specific antigen (PSA) failure among men undergoing radical
      prostatectomy (RP), there was a trend toward a lower risk of recurrence in
      patients with positive bilateral biopsies, suggesting that high-volume,
      unilateral disease was a worse predictor of outcome than an equivalent number of
      positive cores distributed over two lobes. In the current study, the authors
      sought to compare the total percentage of cores with carcinoma directly with the
      percentage of cores from the more involved or dominant side of the prostate with
      carcinoma for their ability to predict outcome among men who underwent RP.
      METHODS: A retrospective survey of 535 patients from the Shared Equal Access
      Regional Cancer Hospital database who underwent RP at 4 different equal-access
      medical centers between 1988 and 2002 was undertaken. The total percentage of
      cores positive was compared with the percentage of cores positive from the
      dominant and nondominant sides for their ability to predict biochemical
      recurrence after RP. The best predictor then was compared with the standard
      clinical variables PSA, biopsy Gleason score, and clinical stage in terms of
      ability to predict time to PSA recurrence after RP using multivariate analysis.
      RESULTS: The adverse pathologic features of positive surgical margins and
      extracapsular extension were significantly more likely to be ipsilateral to the
      dominant side on the prostate biopsy. The percentage of cores positive from the
      dominant side provided slightly better prediction (concordance index [C] = 0.636)
      for PSA failure than the total percentage of cores positive (C = 0.596) and
      markedly better than the percentage of cores from the nondominant side (C =
      0.509). Cutoff points for percentage of cores positive from the dominant side
      were identified (< 34%, 34-67%, and > 67%) that provided significant risk
      stratification for PSA failure (P < 0.001). On multivariate analysis, the
      percentage of cores positive from the dominant side was the strongest independent
      predictor of PSA recurrence (P < 0.001). Biopsy Gleason score (P = 0.017) also
      was a significant, independent predictor of recurrence. There was a trend, which
      did not reach statistical significance, toward an association between greater PSA
      values and biochemical failure (P = 0.052). Combining the PSA level, biopsy
      Gleason score, and percentage of cores positive from the dominant side of the
      prostate resulted in a model that provided a high degree of prediction for PSA
      failure (C = 0.671). CONCLUSIONS: The percentage of cores positive from the
      dominant side of the prostate was a slightly better predictor of PSA recurrence
      than was the total percentage of cores positive. Using the percentage of cores
      from the dominant side along with the PSA level and the biopsy Gleason score
      provided significant risk stratification for PSA failure.

PMID- 14635069
TI  - Hormone therapy adjuvant to external beam radiotherapy for locally advanced
      prostate carcinoma: a complication-adjusted number-needed-to-treat analysis.
AB  - BACKGROUND: Hormone therapy commonly is used to treat metastatic, locally
      advanced, and localized prostate carcinoma. The objective of the current
      investigation was to determine, using the number-needed-to-treat (NNT) method,
      the effect of using hormone therapy to treat locally advanced disease, with
      consideration given to both the complications and the known advantages associated
      with hormone therapy. METHODS: A literature review was performed to determine 1)
      the absolute benefit, based on available clinical endpoints, associated with the
      addition of hormone therapy to external beam radiotherapy for locally advanced
      prostate carcinoma; 2) the incidence of side effects of short-term and long-term
      hormone therapy; and 3) the stepwise progression from biochemical failure to
      death. A model was constructed to estimate the complication/utility-adjusted
      survival detriment resulting from the side effects of short-term (</= 6 months)
      and long-term (> 6 months) hormone therapy, and the absolute/unadjusted and
      complication-adjusted NNTs for the addition of short-term and long-term hormone
      therapy were computed. In all cases, the magnitudes and signs of the NNTs
      obtained were used to gauge the effect of hormone therapy. RESULTS: The
      unadjusted NNTs were positive and in most cases had relatively small magnitudes
      (the greater the NNT, the smaller the benefit) for both short-term and long-term
      hormone therapy; these results were expected, and they suggested that there is a
      strong benefit associated with the use of hormones adjuvant to radiotherapy for
      locally advanced disease. Adjusted NNTs remained positive and had relatively
      small magnitudes even after the introduction into the analysis of complications
      of short-term and long-term hormone therapy. This finding, although weak with
      respect to the effect of short-term hormone therapy on cause-specific survival,
      remained robust over the range of values for utility impairment expected from
      short-term and long-term hormone therapy. CONCLUSIONS: The benefits of short-term
      and long-term hormone therapy for locally advanced prostate carcinoma appear to
      be significant and to outweigh the associated side effects. Long-term therapy
      appears to be better than short-term therapy in terms of virtually all endpoints
      studied, even when the increased incidence of side effects is considered. The
      current investigation was successful in the use of the complication-adjusted NNT
      method for oncologic and radiotherapeutic scenarios in which the results of
      randomized trials could be summarized, adjusted for treatment toxicity, and
      individualized to a given patient.

PMID- 14635070
TI  - Clinical features of patients who present with metastatic prostate carcinoma and
      serum prostate-specific antigen (PSA) levels < 10 ng/mL: the "PSA negative"
      patients.
AB  - BACKGROUND: Although < 1% of men present with prostate-specific antigen (PSA)
      negative prostate carcinoma, in that they have serum PSA levels much lower than
      the tumor burden would suggest, such patients represent a management dilemma. To
      the authors' knowledge, little information exists in the literature regarding
      patterns of disease and response to treatment. The authors wished to define the
      clinical features of this patient group. METHODS: The British Association of
      Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to
      identify the clinical features and outcome of 33 men with metastatic prostate
      carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and
      histopathology were reviewed for each patient. RESULTS: Seventeen patients (51%)
      presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with
      bone pain. Characteristic bone metastases were present in 81% of patients,
      similar to the presentation of men with high serum PSA levels. Hypercalcemia was
      a feature in 9% of patients. Visceral metastases were present in two patients.
      The median response duration to first-line hormone manipulation was 7 months. No
      responses were seen in 11 of 13 patients who received second-line hormones or to
      any third-line treatment. Three of 5 patients who received chemotherapy responded
      but developed recurrent disease within 8 weeks of treatment cessation. The median
      overall survival was 12 months. CONCLUSIONS: The presentation of patients with
      treatment-naive PSA-negative metastatic prostate carcinoma is similar to that of
      patients with high serum PSA levels, but their median survival and response
      duration to first-line hormone therapy are of much shorter duration. Second-line
      hormone therapy is ineffective, but early chemotherapy may be beneficial.
      Hypercalcemia is a particular feature in this group of patients.

PMID- 14635071
TI  - Is endometrial carcinoma intrinsically more aggressive in elderly patients?
AB  - BACKGROUND: The current study was conducted to determine the influence of old age
      (age >/= 70 years) on outcome in a group of patients with endometrial carcinoma
      who were treated with simple hysterectomy followed by adjuvant radiation therapy
      (RT). METHODS: Between November 1987 and May 2000, 405 patients with
      International Federation of Gynecology and Obstetrics (FIGO) Stage IB-II
      endometrial carcinoma were treated with postoperative RT. Intravaginal RT alone
      was given to 77% of patients (median dose, 21grays [Gy] given in 3 fractions).
      Additional postoperative external beam radiation therapy (EBRT) was given to 23%
      of patients (median dose, 45 Gy). Eighty-four patients were age >/= 70 years and
      321 patients were age < 70 years. The two groups were well balanced with regard
      to race, comprehensive surgical staging, aggressive histology, lymphovascular
      invasion, lower uterine segment involvement, cervical involvement, and the use of
      postoperative EBRT. Significantly more patients in the age >/= 70 years group had
      other comorbidities such as obesity, diabetes mellitus, or hypertension (P =
      0.02) and were found to have deep (> 50%) myometrial invasion (P = 0.008).
      RESULTS: With a median follow-up time of 48 months, the 5-year locoregional
      control (LRC), disease-free survival (DFS), and overall survival (OS) rates were
      95%, 91%, and 90% respectively. On multivariate analysis, poor LRC was found to
      be correlated with age >/= 70 years (P = 0.019) and lymphovascular invasion (P =
      0.001). Poor DFS was found to be correlated with age >/= 70 years (P = 0.03),
      lymphovascular invasion (P = 0.01), and aggressive histology (P = 0.001).
      Similarly, poor OS was found to correlate with age >/= 70 years (P = 0.001),
      lymphovascular invasion (P = 0.01), aggressive histology (P = 0.01), and cervical
      involvement (P = 0.02). The same factors that were found to correlate with OS
      (age >/= 70 years, lymphovascular involvement, aggressive histology, and cervical
      involvement) also appeared to correlate with disease-specific survival (P = 0.03,
      P = 0.008, P = 0.001, and P = 0.04, respectively). The 5-year actuarial rates of
      Radiation Therapy Oncology Group late complications that were >/= Grade 3
      (gastrointestinal tract, genitourinary tract, or vagina) were 3% in both groups.
      CONCLUSIONS: Even when treated in a similar fashion, endometrial carcinoma
      patients age >/= 70 years appear to fare worse than younger patients independent
      of other poor prognostic factors. The rate of complications from adjuvant RT,
      despite a higher rate of comorbidity in elderly patients, was found to be similar
      in both age groups. Endometrial carcinoma appears to be intrinsically more
      aggressive in older patients, thus mandating further improvement in their
      treatment strategies.

PMID- 14635072
TI  - Parathyroid carcinoma: is there a role for adjuvant radiation therapy?
AB  - BACKGROUND: The authors proposed to determine risk factors associated with
      postoperative progression of parathyroid carcinoma within the neck (locoregional)
      and to assess the efficacy of postoperative adjuvant radiation therapy in
      preventing disease progression within the neck. METHODS: A retrospective review
      of patients with pathologically confirmed parathyroid carcinoma who underwent
      surgical resection was performed. Risk factors identified on univariate analysis
      were applied in a proportional hazards analysis to identify significant
      independent predictors of locoregional disease progression and cause-specific
      survival after surgical resection. Fifty-seven patients were treated with surgery
      alone (no adjuvant radiation therapy [RT]) and were determined to have sufficient
      follow-up and pathologically confirmed features to be included in the current
      analysis. Four patients were treated with surgery and adjuvant RT. Four patients
      received RT to the neck and mediastinum for unresectable locoregional disease
      progression. Patients were followed for a median of 75.6 months (range, 8.4-358
      months). RESULTS: Twenty-five patients (44%) developed locoregional disease
      progression at a median of 27.1 months after surgery (range, 6.2-138.3 months).
      The univariate analysis revealed that surgical margin status and the institution
      at which the initial surgery was performed were predictive of locoregional
      progression-free survival. The institution at which the initial surgery was
      performed was found to be an independent predictor of cause-specific survival. Of
      the four patients treated with surgery and adjuvant RT, all were alive and
      without disease at the time of last follow-up. All four patients who received RT
      for locoregional disease progression after initial surgery achieved locoregional
      disease control. CONCLUSIONS: Patients with parathyroid carcinoma are reported to
      have a significant risk of locoregional disease progression after surgery alone.
      The results of the current study demonstrated that the risk of postoperative
      disease progression can be predicted by surgical margin status and the
      institution at which the initial surgery is performed. Patients treated with
      surgery and postoperative RT may have a lower risk of locoregional disease
      progression and improved cause-specific survival. RT can be used to provide
      locoregional control of recurrent disease.

PMID- 14635073
TI  - Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from
      patients with mucosal recurrent nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common head and neck
      malignancy in southeastern China and Taiwan. Early detection of the local disease
      followed by timely and appropriate treatment is essential to increasing cure and
      survival rates. Detection of Epstein-Barr virus (EBV) genomic DNA, such as the
      latent membrane protein 1 gene (LMP-1), in patients postirradiation during follow
      up may indicate mucosal recurrence. METHODS: Seventy-one patients with NPC
      underwent serial nasopharyngeal swabs for LMP-1 polymerase chain reaction assay
      before, during, and after irradiation. All of patients achieved a complete
      disease remission of the LMP-1 gene after irradiation that lasted for at least 6
      months. RESULTS: The median LMP-1 disease remission time after the beginning of
      irradiation was 4.3 weeks. Patients with early LMP-1 disease remission (</= 4
      weeks after the beginning of irradiation) and delayed LMP-1 disease remission (>
      4 weeks) had 3-year local control rates of 93.5% and 76.9%, respectively (P =
      0.0529). The LMP-1 gene was detected again (reexpression of LMP-1 [re-LMP-1]) in
      10 patients after irradiation with at least 6 months of follow-up. Nine of 10
      patients (90%) in the re-LMP-1 positive group and 2 of 61 patients (3.3%) in the
      re-LMP-1 negative group developed local recurrence. Mucosal recurrence developed
      in nine patients, and all displayed re-LMP-1. By detecting re-LMP-1 using
      nasopharyngeal swabs, mucosal recurrence was diagnosed with a sensitivity of 100%
      (9 of 9 patients) and a specificity of 98.4% (61 of 62 patients). The 3-year
      overall survival rate, the disease free survival rate for the entire group, and
      the estimated local mucosal control rates in the re-LMP-1 positive and re-LMP-1
      negative groups were 86.5%, 76.5%, 19.4%, and 96.7%, respectively. CONCLUSIONS:
      Expression of EBV LMP-1 in nasopharyngeal swab specimens from patients with
      irradiated/treated NPC can provide a highly sensitive and specific method of
      forecasting mucosal recurrence. This investigation confirmed the reliability and
      feasibility of nasopharyngeal swabs in screening for mucosal recurrences in
      patients with NPC.

PMID- 14635074
TI  - Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for
      patients with early-stage, favorable Hodgkin lymphoma: the experience of the
      Gruppo Italiano Studio Linfomi.
AB  - BACKGROUND: The acknowledged effectiveness of vinblastine, bleomycin, and
      methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has
      been associated with conflicting toxicity reports. METHODS: One hundred forty
      three patients were evaluated clinically and had favorable Stage IA or IIA
      Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM
      schedule combined with extended-field radiotherapy (EF-RT), leaving the choice of
      the therapeutic sequence free. Fifty subsequent patients were treated with a
      slightly modified VBM schedule (VbMp) combined with RT limited to involved fields
      (IF-RT) and delivered only after the end of chemotherapy. In the VbMp schedule,
      intervals between cycles were 21 days instead of 28 days, bleomycin doses were
      reduced, small doses of prednisone were given orally, and the interval before RT
      was prolonged. RESULTS: Clinical response was complete in 96% of patients who
      were treated with VBM plus EF-RT and in 94% of patients who were treated with
      VbMp plus IF-RT. Recurrence rates were nearly identical (12% and 11%,
      respectively) over necessarily different follow-up (91 months and 33 months,
      respectively). Hematologic toxicity was tolerable in both trials, and pulmonary
      side effects were moderate in the first trial and negligible in the second. On
      the whole, treatment was tolerated better when RT followed chemotherapy.
      CONCLUSIONS: The VBM regimen was confirmed to be effective in patients with early
      stage Hodgkin lymphoma. Administration of all cycles before RT improved
      tolerance; pulmonary toxicity probably is mitigated further by reduced bleomycin
      doses, mild prednisone therapy, and a more prolonged resting interval before RT.
      A slightly higher recurrence rate was expectable in the VBM plus IF-RT trial
      despite the actual intensification of vinblastine and methotrexate.

PMID- 14635075
TI  - Risk and timing of hospitalization for febrile neutropenia in patients receiving
      CHOP, CHOP-R, or CNOP chemotherapy for intermediate-grade non-Hodgkin lymphoma.
AB  - BACKGROUND: Hospitalization for chemotherapy-induced febrile neutropenia is
      associated with substantial cost and may negatively impact clinical outcome due
      to associated dose attenuation. METHODS: Medical records of 1355 patients with
      intermediate-grade non-Hodgkin lymphoma receiving cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP) or similar chemotherapy were reviewed. The
      potential risk factors associated with first hospitalization for febrile
      neutropenia were evaluated. RESULTS: In the current study, 230 patients (17%)
      experienced 1 or more hospitalizations for febrile neutropenia and greater than
      one-half of all initial hospitalizations for febrile neutropenia occurred in
      Cycles 1 or 2. Increased risk of hospitalization for febrile neutropenia, based
      on Cox proportional hazards models, was significantly associated with the
      following characteristics: age 65 years or older (hazard ratio [HR] = 1.79; 95%
      confidence interval [95% CI], 1.35-2.37), serum albumin level at presentation
      less than or equal to 3.5 g/dL (HR = 1.34; 95% CI, 1.01-1.78), planned average
      relative dose intensity greater than or equal to 80% (HR = 2.70; 95% CI, 1.47
      4.98), baseline absolute neutrophil count less than 1500/mm3 (HR = 1.98; 95% CI,
      1.28-3.06), and the presence of hepatic disease (HR = 2.18; 95% CI, 1.11-4.28).
      Lack of early granulocyte colony-stimulating factor in Cycles 1 and 2 was also
      associated with increased risk of hospitalization for febrile neutropenia, but
      this did not reach statistical significance. A composite risk score based on
      these potential risk factors effectively distinguished patients at greater risk
      of hospitalization for febrile neutropenia (P < 0.001), the majority of which
      were observed during the first cycle of chemotherapy. CONCLUSIONS: The data from
      the current study demonstrated that the risk of initial hospitalization for
      febrile neutropenia occured early in the course of CHOP-like chemotherapy.
      Identified risk factors for febrile neutropenia hospitalization may facilitate
      the use of targeted supportive care.

PMID- 14635076
TI  - Sequential interleukin 3 and granulocyte-macrophage-colony stimulating factor
      therapy in patients with bone marrow failure with long-term follow-up of
      responses.
AB  - BACKGROUND: Interleukin-3 (IL-3) and granulocyte-macrophage-colony stimulating
      factor (GM-CSF) have synergistic, hematopoietic growth-promoting activity in
      preclinical studies. Because of the paucity of effective therapies for patients
      with chronic bone marrow failure states, the authors studied the biologic
      activity of sequential IL-3/GM-CSF in such patients. METHODS: IL-3 was given
      subcutaneously for 5 days (at escalating doses of 0.15 microg/kg, 0.3 microg/kg,
      0.6 microg/kg, 1.2 microg/kg, 2.5 microg/kg, 5.0 microg/kg, 10.0 microg/kg, or
      15.0 microg/kg per day), and GM-CSF for was given subcutaneously for 9 days (at a
      dose of 5 microg/kg per day; Phase I 3 + 3 design) followed by 14 days of rest
      (total, 2 courses), then maintenance therapy. RESULTS: The majority of 38
      evaluable patients had aplastic anemia or myelodysplastic syndrome. Most patients
      (79%) had neutrophil responses. Ten patients (26%), all of whom were treated with
      IL-3 doses >/= 1.2 microg/kg per day, had platelet responses, with a median
      increase of 132 x 10(9)/L (range, 41-180 x 10(9)/L) over baseline in responders.
      Six patients (16%) had trilineage recovery, which could be durable (the longest
      ongoing at 6.5 years after therapy completion). The most common toxicities were
      low-grade fever, headache, and fatigue. The maximum tolerated doses were IL-3 at
      10 microg/kg per day and GM-CSF at 5 microg/kg per day. CONCLUSIONS: Sequential
      IL-3/GM-CSF effectively raised blood counts in some patients with bone marrow
      failure at doses that were tolerated well. These results indicate that early
      acting growth factors can induce durable, multilineage responses in a subset of
      individuals with bone marrow failure.

PMID- 14635077
TI  - Microscopic analysis of chromium accumulation in the bronchi and lung of chromate
      workers.
AB  - BACKGROUND: It is known that chromium is an inhaled carcinogen and an important
      risk factor in the development of lung carcinoma. METHODS: The authors used a
      microscopic X-ray fluorescence analyzer with transmitted X-ray mapping imaging
      (Horiba, Kyoto, Japan) to measure the accumulation of chromium in 10 resected
      lung tissue specimens and 90 biopsy specimens from chromate workers. RESULTS: The
      maximum chromium accumulation (mean +/- standard deviation) in 10 resected lung
      tissue specimens was 197 +/- 238 counts per second (cps)/mili ampere (mA) (range,
      4-649 cps/mA). Chromium accumulation was scattered in six tissue specimens and
      diffuse in one specimen. Chromium accumulation in the proximal bronchi was less
      than in the bronchioles or subpleural regions of the lung. Chromium accumulation
      was detectable in 63 (70%) of 90 biopsy specimens, and the mean accumulation was
      6.5 +/- 9.2 cps/mA (range, 0-46.5 cps/mA). Chromium detected in bronchial tissue
      specimens was deposited in the bronchial stroma but not in the epithelium. The
      maximum chromium accumulations in dysplasic (n = 3), squamous metaplastic (n =
      10), and normal bronchial epithelia (n = 9) in chromate workers and in normal
      bronchial epithelia (n = 3) in non-chromate workers were 20.2 +/- 5.4, 18.3 +/-
      12.2, 13.2 +/- 13.4, and 3.0 +/- 1.8 cps/mA, respectively. The amount of chromium
      accumulation significantly increased according to the progression of malignant
      change of the bronchial epithelium (P = 0.003). CONCLUSIONS: Previous studies
      found that lung carcinoma with chromate exposure exhibited a variety of genetic
      abnormalities. Considering genetic aberrations and chromium accumulation in these
      premalignant lesions is useful for elucidating the process of carcinogenesis in
      chromium-induced lung carcinoma.

PMID- 14635078
TI  - Expression of tenascin-C in various human brain tumors and its relevance for
      survival in patients with astrocytoma.
AB  - BACKGROUND: Tenascin-C (TN-C), a large extracellular matrix (ECM) glycoprotein
      with a molecular weight of 180-250 kilodaltons, is present in several normal
      adult tissues. TN-C is up-regulated during embryogenesis, in wound healing, and
      in tumor tissues. Glioblastoma multiforme (GBM) is the most frequent and
      malignant astrocytic tumor comprised of poorly differentiated, neoplastic
      astrocytes. Recently, TN-C-based radioimmunotherapy was administered to patients
      with GBM. METHODS: In the current study, the authors used immunohistochemistry to
      conduct a systematic investigation of TN-C distribution patterns in normal human
      brain tissue and in a large variety of brain tumors (n = 485 tumors).
      Immunoreactivity for TN-C was assessed with regard to its localization within
      tumor cells, blood vessels, and ECM using three different monoclonal antibodies
      (clones BC2, BC4, and TN2). RESULTS: In control human brains, a significant
      difference was noted in the expression of TN-C when comparing gray with white
      matter using either Western blot analysis or immunohistochemistry. TN-C was found
      in the white matter of the frontal, temporal, parietal, and occipital lobes and
      in the hippocampus, where the immunoreaction was especially strong in the
      hippocampal formation. In 181 astrocytomas of different grades (World Health
      Organization [WHO] Grade 2-4), TN-C immunopositivity was seen to varying degrees
      in the cellular and stromal components of the tumor and in tumor-associated
      vessels. Glioblastomas (n = 113 tumors) showed strong immunopositivity in the
      vessels and moderate immunopositivity of the ECM. A statistically significant
      reduction of TN-C immunopositivity in tumor-associated vessels or ECM was
      observed in anaplastic astrocytomas (WHO Grade 3) compared with GBM (WHO Grade
      4). A Kaplan-Meier analysis showed that patients who had GBM lesions that lacked
      TN-C immunopositivity in the ECM had a significantly longer survival (median, 28
      months; standard error, 7.8 months) (n = 12 patients) compared with patients who
      had GBM lesions with TN-C immunopositivity (median, 12 months; standard error,
      1.6 months) (n = 87 patients). In meningiomas (n = 24 tumors), the neoplastic
      cells, the ECM of the tumor, and the vessels were TN-C negative. In schwannomas
      (n = 31 tumors), the tumor cells were TN-C negative; whereas, in > 50% of tumors,
      the vessels and the ECM of regressively altered tumor areas were positive. In
      metastatic carcinomas (n = 53 tumors), the tumor cells were negative; seldom were
      vessels stained positive for TN-C. Focal areas of the ECM, often accompanied with
      fibrotic changes, were immunopositive for TN-C. CONCLUSIONS: The most constant TN
      C immunopositivity was noted in the ECM of the fibrotic stroma in highly
      malignant brain tumors and along the tumor border, especially in high-grade
      astrocytomas. The current results suggest that TN-C expression may be correlated
      with the grade of malignancy in astrocytic tumors and that the presence or
      absence of TN-C expression in the stroma of astrocytic tumors may play a not yet
      clearly understood role in shortening or prolonging, respectively, the survival
      of patients.

PMID- 14635079
TI  - Impact of highly active antiretroviral therapy on the presenting features and
      outcome of patients with acquired immunodeficiency syndrome-related Kaposi
      sarcoma.
AB  - BACKGROUND: The objective of the current study was to evaluate the impact of
      highly active antiretroviral therapy (HAART) on clinical characteristics of
      presentation and the natural history of Kaposi sarcoma (KS) in patients already
      receiving HAART at the time of KS diagnosis. METHODS: The authors conducted a
      retrospective cohort study comparing epidemiologic, clinical, and outcome data
      for 160 patients who were naive to HAART at the time of KS diagnosis (KS-naive)
      with the corresponding data for 51 patients already receiving HAART at the time
      of KS diagnosis (KS-HAART). The analysis included all patients with a diagnosis
      of KS since January 1996 within two Italian cohorts of patients with human
      immunodeficiency virus. RESULTS: Immunologic and virologic status at the time of
      KS diagnosis were significantly more favorable in the KS-HAART group than in the
      KS-naive group. The frequency of cutaneous involvement was similar in both
      groups, but cutaneous disease was more indolent among KS-HAART patients, with 1
      anatomic site of involvement in 9 patients (21%) and less than 10 lesions in 26
      patients (60%), compared with 16 patients (12%; P = 0.06) and 47 patients (34%; P
      = 0.01), respectively, in the KS-naive group. A smaller proportion of KS-HAART
      patients presented with visceral disease (24% vs. 39%; P = 0.06); in particular,
      gastrointestinal tract involvement was significantly less frequent among KS-HAART
      patients (14%) compared with KS-naive patients (28%; P = 0.05). Median survival
      was not reached in either group, and the 3-year survival rates of KS-HAART
      patients (64%) and KS-naive patients (78%) were not significantly different.
      CONCLUSIONS: The data from the current study indicate that KS exhibits a less
      aggressive presentation in patients already receiving HAART compared with
      patients who are naive to HAART at KS diagnosis. Natural history and outcome do
      not appear to be influenced by the initiation of HAART before development of KS.

PMID- 14635080
TI  - Pattern of disease recurrence and prognostic factors in patients with
      osteosarcoma treated with contemporary chemotherapy.
AB  - BACKGROUND: The goal of the current study was to define the clinical features and
      outcome of recurrent osteosarcoma (OS) in children and young adults initially
      treated with contemporary chemotherapy. METHODS: The authors reviewed the
      clinical features, therapy, and outcome for 59 patients from the Mayo Clinic
      (Rochester, MN) and Children's Hospital and Regional Medical Center (Seattle,
      WA). They were diagnosed initially with OS between January 1990 and December
      2000, received multiagent chemotherapy (most frequently cisplatin, doxorubicin,
      high-dose methotrexate, and ifosfamide), and developed disease recurrence after
      achieving an initial complete response (CR). RESULTS: The most common site of
      initial disease recurrence was the lung only (n = 36 patients), followed by
      distant bone (n =8 patients), combined lung and other sites (n =7 patients), and
      other sites (n =8 patients). The median time to first disease recurrence was 15
      months (range, 2-92 months) from the initial diagnosis. Thirty patients with
      isolated pulmonary recurrence achieved a second CR, either with surgery alone (n
      =15 patients) or surgery and salvage chemotherapy (n =15 patients). For this
      group, the 4-year disease-free survival (DFS) and overall survival rates were 7%
      (95% confidence interval [95% CI], 0-16%) and 28% (95% CI, 11-45%), respectively.
      For all 59 patients with recurrent OS, the 4-year DFS and overall survival rates
      were 6% (95% CI, 0-12%) and 23% (95% CI, 10-36%), respectively. The only factors
      associated with improved DFS and overall survival rates were unilateral pulmonary
      recurrence, solitary pulmonary nodule at recurrence, more than 24 months between
      the initial diagnosis and first disease recurrence, and achievement of a second
      CR. CONCLUSIONS: The DFS and overall survival rates for recurrent OS after
      contemporary therapy remained poor even for patients with isolated pulmonary
      recurrence. Therefore, new treatment strategies are needed.

PMID- 14635081
TI  - Single and multiple metachronous osteosarcoma tumors after therapy.
AB  - BACKGROUND: The objective of the current study was to determine the incidence,
      clinical and pathologic characteristics, and outcome of patients with
      conventional osteosarcoma who developed metachronous tumors after treatment for
      the primary tumor and prevention of pulmonary metastases. METHODS: The medical
      records of 270 pediatric patients (younger than age 18 years) were reviewed. The
      prevention and absence of pulmonary metastases was confirmed by chest radiographs
      and computerized scans of the lungs. Radionuclide bone scans were used to confirm
      the absence of skeletal metastases. RESULTS: Eleven patients with metachronous
      tumors were identified. Index primary tumors involved the femur (n = 8), the
      tibia (n = 2), and the radius (n = 1). Single metachronous tumors developed in
      the femur (n = 6), in the humerus (n = 1), and multifocal in multiple bones (n =
      4). Two patients later developed second metachronous tumors. The interval between
      identification of the primary tumor to development of the single metachronous
      tumors varied from 11 months to 78 months and from 12 months to 42 months for
      synchronous multifocal tumors. Metachronous tumors were treated with single-agent
      cisplatin or ifosfamide. Only 1 patient experienced > 90% tumor necrosis.
      Pulmonary metastases were not detected in 10 of 11 patients at the time
      metachronous tumors were discovered. In the 11th patient, synchronous pulmonary
      metastasis with the metachronous tumor was noted. Three patients had a prior
      history of bilateral retinoblastoma. The Li-Fraumeni syndrome may have been
      present in another patient. Six patients died. Five patients have survived for
      20+ to 50+ months after the appearance, treatment, and resection of metachronous
      tumors. CONCLUSIONS: With improvement in the cure rate, metachronous osteosarcoma
      should be recognized as an important sequela in long-term survivors. The etiology
      of this disease is unknown. Speculation rests on a skeletal multicentric origin,
      which includes an inherited predisposition to develop osteosarcoma in
      retinoblastoma and in the Li-Fraumeni syndrome. Meticulous follow-up is required
      to permit early detection and successful therapeutic intervention.

PMID- 14635082
TI  - Impact of race on outcome after definitive radiotherapy for squamous cell
      carcinoma of the head and neck.
AB  - BACKGROUND: The objective of the current study was to evaluate the impact of race
      (black vs. white) on the outcome of patients with invasive squamous cell
      carcinoma of the head and neck. METHODS: Between 1983 and 1997, 686 patients
      completed definitive, twice-daily radiotherapy (RT) alone or combined with a
      planned neck dissection; no patients received adjuvant chemotherapy. The minimum
      follow-up was 2 years, and median follow-up was 7 years for living patients. No
      patients were lost to follow-up. Fifty-five patients were black (8%). RESULTS:
      Although the two groups had similar 5-year local-regional control rates (black
      patients vs. white patients: 70% vs. 76%, respectively; P = 0.275), black
      patients had double the risk for distant recurrence compared with white patients
      (27% vs. 13%; P = 0.012). The 5-year cause-specific and absolute survival rates
      were lower for black patients (52% vs. 74% [P = 0.001] and 29% vs. 52% [P <
      0.001], respectively). Multivariate analyses revealed that race was an
      independent predictor of freedom from distant metastasis (P = 0.013), cause
      specific survival (P = 0.005), and absolute survival (P < 0.001). CONCLUSIONS:
      Although equal local-regional control rates can be achieved in black patients and
      white patients with squamous cell carcinoma of the head and neck, the risk of
      distant recurrence was significantly higher in black patients and resulted in
      decreased survival. Reevaluation of current strategies for pretreatment
      metastatic work-ups and development of more effective systemic therapy will be
      key to improving the survival disparity in this group.

PMID- 14635083
TI  - Improved prevention of moderately emetogenic chemotherapy-induced nausea and
      vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist:
      results of a phase III, single-dose trial versus dolasetron.
AB  - BACKGROUND: Palonosetron, a highly selective and potent 5-HT(3) receptor
      antagonist with a strong binding affinity and a long plasma elimination half-life
      (approximately 40 hours), has shown efficacy in Phase II trials in preventing
      chemotherapy-induced nausea and vomiting (CINV) resulting from highly emetogenic
      chemotherapy. The current Phase III trial evaluated the efficacy and safety of
      palonosetron in preventing acute and delayed CINV after moderately emetogenic
      chemotherapy. METHODS: In the current study, 592 patients were randomized to
      receive a single, intravenous dose of palonosetron 0.25 mg, palonosetron 0.75 mg,
      or dolasetron 100 mg, 30 minutes before receiving moderately emetogenic
      chemotherapy. The primary efficacy endpoint was the proportion of patients with a
      complete response (CR; defined as no emetic episodes and no rescue medication)
      during the first 24 hours after chemotherapy. Secondary endpoints included
      assessment of prevention of delayed emesis (2-5 days postchemotherapy). RESULTS:
      In the current study, 569 patients received study medication and were included in
      the intent-to-treat efficacy analyses. CR rates during the first 24 hours were
      63.0% for palonosetron 0.25 mg, 57.1% for palonosetron 0.75 mg, and 52.9% for
      dolasetron 100 mg. CR rates during the delayed period (24-120 hours after
      chemotherapy) were superior for palonosetron compared with dolasetron. Adverse
      events (AEs) were mostly mild to moderate and not related to study medication,
      with similar incidences among groups. There were no serious drug-related AEs.
      CONCLUSIONS: A single dose of palonosetron is as effective as a single dose of
      dolasetron in preventing acute CINV and superior to dolasetron in preventing
      delayed CINV after moderately emetogenic chemotherapy, with a comparable safety
      profile for all treatment groups.

PMID- 14635084
TI  - Imatinib mesylate causes hypopigmentation in the skin.
AB  - BACKGROUND: Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR
      ABL protein in CML, c-kit (KIT) and platelet-derived growth factor receptors. In
      clinical trials with imatinib mesylate, common side effects of nausea, emesis,
      diarrhea, periorbital edema, fluid retention, and myelosuppression have been
      documented. METHODS: In this case series, the authors describe unique clinical
      findings of skin hypopigmentation in six patients with CML who were treated with
      imatinib mesylate. RESULTS: Most patients developed onset of skin
      hypopigmentation within the first month of treatment and all of the patients
      experienced additional drug toxicity. Despite patient susceptibility to toxicity,
      the presence of hypopigmentation did not appear to predict leukemic cell response
      or clinical outcome. All six patients established a hematologic response but only
      two patients had a complete cytogenetic response. Imatinib mesylate induced
      hypopigmentation also appeared to be reversible and potentially dose related.
      CONCLUSION: Skin hypopigmentation is a benign side effect from imatinib mesylate
      treatment that appears to be reversible upon discontinuation or dose reduction.
      Several lines of evidence have previously reported that KIT and its ligand stem
      cell factor (SCF) have a regulatory role in melanocyte development and survival,
      suggesting a rational mechanism of action for imatinib mesylate in the
      pathogenesis of hypopigmentation. The signal transduction mechanism currently is
      believed to involve SCF ligand binding of KIT and downstream activation of MAP
      kinase (Erk-2). Microphthalmia (Mi), a basic helix-loop-helix leucine zipper
      (bHLHZip) transcription factor, is phosphorylated by MAP kinase at a serine
      residue (S73). Once phosphorylated, Mi transactivates the tyrosine pigmentation
      gene promoter and affects pigment production.

PMID- 14635085
TI  - A phase II study of topotecan with vincristine and doxorubicin in children with
      recurrent/refractory neuroblastoma.
AB  - BACKGROUND: A Phase II trial in children with advanced neuroblastoma was carried
      out in five Italian institutions to evaluate the antitumor activity and
      tolerability of topotecan followed by vincristine and doxorubicin. METHODS:
      Children older than age 1 year with Stage III or Stage IV neuroblastoma, all of
      whom had been treated previously with chemotherapy and were diagnosed with either
      refractory or recurrent disease, were treated with topotecan at an intravenous
      dose of 1.5 mg/m(2) (the dose was 0.75 mg/m(2) for patients who were treated
      within 1 year of previous megatherapy) per day for 5 days followed by 48-hour
      intravenous infusions of 2 mg/m(2) vincristine and 45 mg/m(2) doxorubicin. Cycles
      of therapy were repeated every 3 weeks. RESULTS: Twenty-five patients (2 with
      Stage III disease and 23 with Stage IV disease; 19 with refractory disease and 6
      with recurrent disease) were treated with a total of 115 cycles. Four patients
      had complete responses, 12 patients had partial responses, 4 patients had minor
      responses or stable disease, and 5 patients had tumor progression. The overall
      response rate (including complete and partial responses) was 64% (95% confidence
      interval, 43-82%). Fifteen patients were alive at the time of the current report
      and were progression free at 4-16 months (median, 9 months) after the first
      course of this treatment. Toxicity generally was limited to the hematopoietic
      system. Dose-limiting toxicity was observed in only 1 patient (Grade 4 liver
      toxicity). There were no deaths due to infectious or toxic causes. CONCLUSIONS:
      The topotecan-vincristine-doxorubicin combination was active and well tolerated
      in previously treated patients with advanced neuroblastoma.

PMID- 14635086
TI  - Change in smoking status after spiral chest computed tomography scan screening.
AB  - BACKGROUND: Cancer screening may provide a "teachable moment" for the reduction
      of high-risk behaviors. The current study evaluated smoking behavior changes in
      current and former smokers after low-dose, fast spiral chest computed tomography
      scan (CT) screening for lung carcinoma. METHODS: The study was comprised of 901
      current smokers and 574 former smokers who participated in a low-dose, fast
      spiral chest CT scan screening study for lung carcinoma. Demographic, pulmonary
      function, screening recommendations, and smoking history variables were evaluated
      as predictors of self-reported point prevalence smoking abstinence 1 year after
      screening. RESULTS: Of the current smokers at baseline, 14% reported smoking
      abstinence at follow-up. Older age and poorer lung function were associated with
      smoking abstinence. Ninety percent of former smokers reported smoking abstinence
      at a 1-year of follow-up. A longer duration of smoking abstinence at baseline was
      found to be predictive of abstinence in this group. CONCLUSIONS: The 14% smoking
      abstinence rate was higher than would be expected for spontaneous rates of
      smoking cessation. Therefore, screening may provide a teachable moment for
      smokers. Low-dose, fast spiral chest CT scan screening recommendations were not
      found to be associated with smoking behavior change in either group. Further
      research is needed to evaluate the potential avenues through which lung carcinoma
      screening can be used as an opportunity for providing effective nicotine
      interventions.

PMID- 14635087
TI  - Attitudes of medical oncologists toward palliative care for patients with
      advanced and incurable cancer: report on a survery by the European Society of
      Medical Oncology Taskforce on Palliative and Supportive Care.
AB  - BACKGROUND AND METHODS: In part of a quality improvement program, the European
      Society of Medical Oncology (ESMO) surveyed its membership regarding their
      involvement in and attitudes toward the palliative care (PC) of patients with
      advanced cancer. RESULTS: Of 895 members who responded, 82.5% were European and
      12.1% were American. Sixty-nine percent of respondents reported that patients
      with advanced cancer constituted a major proportion of their practice; for 22% of
      respondents, patients with advanced cancer constituted most of their practice.
      Only a minority of respondents collaborated often with a PC care specialist
      (35%), a palliative home care service (38%), an in-patient hospice (26%), or a
      psychologist (33%). In response to questions regarding specific involvement in PC
      clinical tasks, respondents were involved more commonly in treating physical
      symptoms, such as pain (93%), fatigue (84%), and nausea/emesis (84%), than in
      managing psychological symptoms and end-of-life care issues, such as
      depression/anxiety (65%), existential distress (29%), or delirium (12%). Forty
      three percent of respondents reported that they directly administered end-of-life
      care often, and 74% reported that they derived satisfaction from their
      involvement in end-of-life care. Overall, 88.4% of respondents endorsed the
      belief that medical oncologists should coordinate the end-of-life care for their
      patients, but a substantial minority (42%) felt that they were trained
      inadequately for this task. Positive attitudes toward PC were correlated highly
      with the degree of direct involvement in PC practice. Practitioners in private
      practice or teaching hospitals had substantially more positive attitudes
      regarding PC compared with physicians based in comprehensive cancer centers (P <
      0.05). Although most of the responding medical oncologists expressed positive
      views regarding their involvement in the PC of patients with advanced cancer and
      dying patients, 15% of respondents had pervasively negative views. CONCLUSIONS:
      Most ESMO oncologists recognize the importance of PC and supportive care for
      patients with advanced cancer. Despite this, many are prepared inadequately for
      these tasks, and actual participation levels commonly are suboptimal.

PMID- 14635088
TI  - Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific
      antigen production in human LNCaP prostate carcinoma cells.
AB  - BACKGROUND: Indole-3-carbinol (I3C), a naturally occurring component of Brassica
      vegetables, such as cabbage, broccoli, and Brussels sprouts, is a promising
      anticancer agent for certain reproductive tumor cells. The objective of the
      current study was to characterize the cell cycle effects of I3C in human prostate
      carcinoma cells. METHODS: The incorporation of [(3)H]thymidine and flow cytometry
      of propidium iodide-stained nuclei were used to monitor I3C-regulated changes in
      prostate carcinoma cell proliferation and cell cycle progression. Western
      blotting was used to document expression changes in cell cycle components and
      prostate-specific antigen (PSA) levels. The enzymatic activities of cyclin
      dependent kinases (CDK) were tested by in vitro protein kinase assays using the
      retinoblastoma protein as a substrate. RESULTS: I3C suppressed the growth of
      LNCaP prostate carcinoma cells in a dose-dependent manner by inducing a G1 block
      in cell cycle progression. I3C selectively inhibited the expression of CDK6
      protein and transcripts and strongly stimulated the production of the p16 CDK
      inhibitor. In vitro protein kinase assays revealed the striking inhibition by I3C
      of immunoprecipitated CDK2 enzymatic activity and the relatively minor down
      regulation of CDK4 enzymatic activity. In LNCaP prostate carcinoma cells, I3C
      treatment inhibited production of PSA, whereas combinations of I3C and the
      androgen antagonist flutamide more effectively inhibited DNA synthesis and PSA
      levels compared with either agent alone. CONCLUSIONS: The results of the current
      study demonstrated that I3C has a potent antiproliferative effect in LNCaP and
      other human prostate carcinoma cells. These findings implicate this dietary
      indole as a potential chemotherapeutic agent for controlling the growth of human
      prostate carcinoma cells.

PMID- 14635089
TI  - Positive surgical margins and ipsilateral breast tumor recurrence predict disease
      specific survival after breast-conserving therapy.

PMID- 14635091
TI  - Sentinel lymph nodes.

PMID- 14635094
TI  - Understanding base-assisted desulfurization using a variety of disulfide-bridged
      peptides.
AB  - A recently rediscovered reaction of base-assisted lanthionine formation has been
      applied to several systems of disulfide-bridged peptides. In addition to
      previously described nonapeptides consisting of i, i+3 cystine linkages, the
      reaction has now been extended to systems consisting of shorter (i, i+2) and
      longer (i, i+4) disulfide bridges. The desulfurization reaction is also
      compatible with disulfide bridges formed through homocysteines and
      penicillamines, yielding unusual amino acids such as cystathionine and beta,beta
      dimethyl lanthionine (referred to as "penthionine") in a peptide chain,
      respectively. Systematic study of this transformation has provided several new
      insights into its mechanism. We have observed formation of dehydroalanine and
      dehydrovaline residues resulting from i, i+2-bridged cysteines and i, i+3-bridged
      cysteine/penicillamine peptides, respectively, thereby supporting a beta
      elimination/Michael-addition mechanism for this transformation. Amino acid
      analysis and NMR data from total correlation spectroscopy (TOCSY) and (1)H-(13)C
      heteronuclear single quantum correlation (HSQC) experiments show three
      diastereomeric lanthionine-bridged peptides in the product mixture. But in the
      case of desulfurization of a cysteine/homocysteine containing disulfide-bridged
      peptide, Michael addition appears to be stereoselective, yielding a single
      stereoisomer of cystathionine within the peptide. According to molecular modeling
      and CD spectroscopy, constrained peptides such as those containing penicillamine
      are less likely to undergo facile desulfurization. Flexibility of the torsional
      angles (C(alpha)H-C(alpha)-C(beta)-S) corresponding to the cysteine residues and
      temperature appear to be contributing factors determining the extent of
      desulfurization.

PMID- 14635095
TI  - Synthesis and evaluation of derivatives of leucine enkephalin as potential
      affinity labels for delta opioid receptors.
AB  - As part of an effort to develop peptide-based affinity labels for opioid
      receptors, [Leu(5)]enkephalin (LeuEnk) and DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr),
      potent agonists for delta receptors, were selected as the parent peptides for
      further modification. The affinity label derivatives were prepared using standard
      Fmoc solid-phase peptide synthesis in conjunction with Fmoc-Phe(p-NHAlloc) (Fmoc:
      9-flourenylmethoxycarbonyl;) and selective modification of the p-amino group on
      this residue. The electrophilic isothiocyanate and bromoacetamide groups were
      introduced into the para position of Phe(4); the corresponding free amine
      containing peptides were also prepared for comparison. The pure peptides were
      evaluated in radioligand binding assays using Chinese hamster ovary (CHO) cells
      expressing delta and micro opioid receptors. Modification of Phe(4) in LeuEnk and
      DTLET significantly decreased delta-receptor binding affinity (40 to >2,000
      fold). Among the synthesized analogues, [Phe(p-NH(2))(4)]DTLET showed the highest
      delta-receptor binding affinity (IC(50) = 39 nM) and enhanced selectivity for
      delta receptors compared to DTLET while other derivatives exhibited much lower
      delta receptor affinity. The differences in affinities between the two series of
      analogues and between the derivatives of LeuEnk and N,N-dibenzyl[Leu(5)]Enk
      reported previously suggest subtle differences in interactions of Phe(4) with
      delta receptors depending on other modifications in the sequences.

PMID- 14635096
TI  - The structure of tri-proline in water probed by polarized Raman, Fourier
      transform infrared, vibrational circular dichroism, and electric ultraviolet
      circular dichroism spectroscopy.
AB  - Tripeptidesserve as model systems for understanding the so-called random-coil
      state of peptides and proteins. While it is well known that polyproline or
      proline-rich polypeptides adopt the very regular polyproline-II (PPII) or left
      handed 3(1)-helix conformation, it was thus far not clear whether this is also
      the predominant structure adopted by proline-containing tripeptides. To clarify
      this issue, we have investigated the amide I' band profile in the ir, isotropic,
      and anisotropic Raman, and vibrational circular dichroism (VCD) spectrum of
      cationic and zwitterionic tri-proline in D(2)O. The data were analyzed by
      modifying a recently developed algorithm, which allows one to obtain the central
      dihedral angles of tripeptides from the amide I' band intensities (R. Schweitzer
      Stenner, Biophysical Journal, 2002, Vol. 83, pp. 523-532). Our analysis revealed
      that the peptide adopts a nearly canonical PPII structure in water with psi and
      phi values in the range of 175 degrees -165 degrees and -70 degrees -(-80 degrees
      ), respectively. This is fully confirmed by the respective electronic ultraviolet
      CD spectra. Our result indicates that the strong PPII propensity of trans proline
      results from local interactions between the pyrrolidine ring and the backbone and
      is not due to any long-range interactions.

PMID- 14635097
TI  - Tryptophan as a probe for acid-base equilibria in peptides.
AB  - We present results of time resolved fluorescence measurements performed in
      Tryptophan (Trp) derivatives and Trp-containing peptides in the pH range 3.0
      11.0. For each compound a set of decay profiles measured in a given range of pH
      values was examined as a whole, using the global analysis technique. The data
      were fitted to two or three lifetime components and the analysis allowed the
      monitoring of the changes in the concentration of the different species
      contributing to the total fluorescence in that pH interval. The decay components
      were sensitive to the ionization state of groups neighboring the indol ring, and
      pK values for the equilibrium between protonated and deprotonated species were
      obtained from the preexponential factor of the lifetime components. In Trp,
      protonation of the amino terminal of the rotamer having electron transfer rate
      comparable to fluorescence decay rates was responsible for the interconvertion of
      a long lifetime component, to the 2.9 ns component usually observed in neutral
      pH. Trpbond;X peptides also have a single rotamer dominating the decay that is
      quenched by NH(3) (+). X-Trp peptides seem to be conformationally less
      restricted, and it is possible that rotamers interconvertion occur in high pH,
      increasing the population of nonquenched rotamers. Interconvertion between
      rotameric conformations of Trp are also present in the titration of ionizable
      groups in the side chain of peptides like His-Trp and Glu-Trp and control of pH
      is essential to the correct interpretation of fluorescence data in the study of
      peptides having such groups near to the Trp residue.

PMID- 14635098
TI  - The probability distribution of side-chain conformations in [Leu] and
      [Met]enkephalin determines the potency and selectivity to mu and delta opiate
      receptors.
AB  - The structure of enkephalin, a small neuropeptide with five amino acids, has been
      simulated on computers using molecular dynamics. Such simulations exhibit a few
      stable conformations, which also have been identified experimentally. The
      simulations provide the possibility to perform cluster analysis in the space
      defined by potentially pharmacophoric measures such as dihedral angles, side
      chain orientation, etc. By analyzing the statistics of the resulting clusters,
      the probability distribution of the side-chain conformations may be determined.
      These probabilities allow us to predict the selectivity of [Leu]enkephalin and
      [Met]enkephalin to the known mu- and delta-type opiate receptors to which they
      bind as agonists. Other plausible consequences of these probability distributions
      are discussed in relation to the way in which they may influence the dynamics of
      the synapse.

PMID- 14635099
TI  - Molecular dynamics simulations of Trp side-chain conformational flexibility in
      the gramicidin A channel.
AB  - Gramicidin A (gA) is prototypical peptide antibiotic and a model ion channel
      former. Configured in the solid-state NMR beta(6.5)-helix channel conformation,
      gA was subjected to 1-ns molecular dynamics (MD) gas phase simulations using the
      all-atom charmm22 force field to ascertain the conformational stability of the
      Trp side chains as governed by backbone and neighboring side-chain contacts.
      Three microcanonical trajectories were computed using different initial atomic
      velocities for each of twenty different initial structures. For each set, one of
      the four Trp side chains in each monomer was initially positioned in one of the
      five non-native conformations (A. E. Dorigo et al., Biophysical Journal, 1999,
      Vol. 76, 1897-1908), the other Trps being positioned in the native state, o1. In
      three additional control simulations, all Trps were initiated in the native
      conformation. After equilibration, constraints were removed and subsequent
      conformational changes of the initially constrained Trp were measured. The chi(1)
      was more flexible than chi(2.1). The energetically optimal orientation, o1
      (Dorigo et al., 1999), was the most stable in all four Trp positions (9, 11, 13,
      15) and remained unchanged for the entire 1 ns simulation in 19 of 24 trials.
      Changes in chi(1) from each of the 5 suboptimal states occur readily. Two of the
      non-native conformations reverted readily to o1, whereas the other three
      converted to an intermediate state, i2. There were frequent interconversions
      between i2 and o1. We speculate that experimentally observed Trp stability is
      caused by interactions with the lipid-water interface, and that stabilization of
      one of the suboptimal conformations in gA, such as i2, by lipid headgroups could
      produce a secondary, metastable conformational state. This could explain recent
      experimental studies of differences in the channel conductance dispersity between
      gA and a Trp-to-Phe gA analog, gramicidin M (gM, J. C. Markham et al., Biochimica
      et Biophysica Acta, 2001, Vol. 1513, 185-192).

PMID- 14635100
TI  - Somatic NF1 mutation spectra in a family with neurofibromatosis type 1: toward a
      theory of genetic modifiers.
AB  - Neurofibromatosis type 1 (NF1), an autosomal dominantly-inherited disorder, is
      mainly characterized by the occurrence of multiple dermal neurofibromas and is
      caused by mutations in the NF1 gene, a tumor suppressor gene. The variable
      expressivity of the disease and the lack of a genotype/phenotype correlation
      prevents any prediction of patient outcome and points to the action of genetic
      factors in addition to stochastic factors modifying the severity of the disease.
      The analysis of somatic NF1 gene mutations in neurofibromas from NF1 patients
      revealed that each neurofibroma results from an individual second hit mutation,
      indicating that factors that influence somatic mutation rates may be regarded as
      potential modifiers of NF1. A mutational screen of numerous neurofibromas from
      two NF1 patients presented here revealed a predominance of point mutations, small
      deletions, and insertions as second hit mutations in both patients. Seven novel
      mutations are reported. Together with the results of studies that showed LOH as
      the predominant second hit in neurofibromas of other patients, our results
      suggest that in different patients different factors may influence the somatic
      mutation rate and thereby the severity of the disease.

PMID- 14635101
TI  - Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non
      polyposis colorectal cancer: identification of novel and recurrent deletions by
      MLPA.
AB  - Gene dosage abnormalities account for a significant proportion of the mutations
      in genes tested in DNA diagnostic laboratories. Detection of these changes has
      proved a challenge as the methods available to date are time consuming or
      unreliable. The multiplex ligation-dependent probe assay (MLPA) is a new
      technique allowing relative quantification of up to 40 different nucleic acid
      sequences in a single reaction tube. We have evaluated MLPA for potential use in
      the diagnostic setting against the following criteria: accuracy, reagent cost,
      hands-on time, reliability, and retests required. A total of 215 UK patients
      referred for genetic testing on the basis of a family history consistent with
      autosomal dominant hereditary non-polyposis colorectal cancer (HNPCC or Lynch
      syndrome) were tested by MLPA. Of these, 12 cases with deletions of one or more
      exons were identified, six with MLH1 deletions and six with MSH2 deletions. Test
      failure rates were less than 5% and overall mutation detection sensitivity in
      this series was increased by approximately 50% by the inclusion of MLPA for an
      additional testing cost of about 10%. Two novel mutations in MSH2 and 10 novel
      point mutations in MLH1 were also identified during the course of this study. We
      conclude that MLPA is a cost effective and robust gene dosage method that can be
      readily adopted by diagnostic services. Comprehensive mutation scanning for MSH2
      and MLH1 is incomplete without gene dosage analysis.

PMID- 14635102
TI  - Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical
      and biochemical phenotype with genotype.
AB  - Cystathionine beta-synthase (CBS) deficiency is a rare autosomal recessive
      disorder that is the most frequent cause of clinical homocystinuria. Patients not
      treated in infancy have multi-systems disorders including dislocated lenses,
      mental deficiency, osteoporosis, premature arteriosclerosis, and thrombosis. In
      this paper, we examine the relationship of the clinical and biochemical
      phenotypes with the genotypes of 12 CBS deficient patients from 11 families from
      the state of Georgia, USA. By DNA sequencing of all of the coding exons we
      identified mutations in the CBS genes in 21 of the 22 possible mutant alleles.
      Ten different missense mutations were identified and one novel splice-site
      mutation was found. Five of the missense mutations were previously described
      (G307S, I278T, V320A, T353M, and L101P), while five were novel (A226T, N228S,
      A231L, D376N, Q526K). Each missense mutation was tested for function by
      expression in S. cerevisiae and all were found to cause decreased growth rate and
      to have significantly decreased levels of CBS enzyme activity. The I278T and
      T353M mutations accounted for 45% of the mutant alleles in this patient cohort.
      The T353M mutation, found exclusively in four African American patients, was
      associated with a B(6)-nonresponsive phenotype and detection by newborn screening
      for hypermethioninemia. The I278T mutation was found exclusively in Caucasian
      patients and was associated with a B(6)-responsive phenotype. We conclude that
      these two mutations occurred after ethnic socialization and that the CBS genotype
      is predictive of phenotype.

PMID- 14635103
TI  - Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene
      and functional analysis of 27 novel disease-causing mutations in patients with
      SSADH deficiency.
AB  - Succinate semialdehyde dehydrogenase (SSADH; ALDH5A1) deficiency, a rare
      metabolic disorder that disrupts the normal degradation of GABA, gives rise to a
      highly heterogeneous neurological phenotype ranging from mild to very severe. The
      nature of the mutation has so far been reported in patients from six families
      world wide and eight different mutations were described. Here we report the
      mutational spectrum in 48 additional unrelated families of different geographic
      origin. We detected 27 novel mutations at the cDNA level, of which 26 could be
      attributed to changes at the genomic level. Furthermore, six mutations were
      detected that did not strongly affect SSADH activity when expressed in HEK 293
      cells and are considered nonpathogenic allelic variants. Twenty of the mutations
      were only found in one family. The spectrum of disease-causing mutations from all
      patients sequenced thus far consists of 25 point mutations, four small
      insertions, and five small deletions. Seven of these mutations affect splice
      junctions, seven are nonsense mutations, and 12 are missense mutations. Although
      there were no mutational hotspots or prevalent mutations responsible for a
      significant number of cases, 14 out of 37 (38%) of the missense alleles were
      present in exon 4 or 5. With one exception, the missense mutations we consider to
      be causative of SSADH deficiency reduced the SSADH activity to less than 5% of
      the normal activity in our in vitro expression system. This indicates that
      residual expression is not likely to be an important factor contributing to the
      large phenotypic differences observed among different families and even among
      siblings, suggesting that other modifying factors are of great importance in
      disease pathology.

PMID- 14635104
TI  - Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF).
AB  - Inherited hearing impairment affects one in 2,000 newborns. Nonsyndromic
      prelingual forms are inherited mainly as autosomal recessive traits, for which 16
      genes are currently known. Mutations in the genes encoding connexins 26 and 30
      account for up to 50% of these cases. However, the individual contribution of the
      remaining genes to the whole remains undetermined. In addition, for most of the
      genes there is a need for studies on genotype-phenotype correlations, to identify
      distinctive clinical features which may direct the molecular diagnosis to
      specific genes. Here we present a mutation analysis and a genotype-phenotype
      correlation study on the gene encoding otoferlin (OTOF), responsible for the
      DFNB9 subtype of prelingual hearing impairment. Four novel mutations were
      identified: c.2122C>T (p.Arg708Ter), c.4275G>A (p.Trp1425Ter), c.4362+2T>G, and
      c.5860_5862delATC (p.Ile1954del). A total of 37 subjects with mutations in OTOF
      were studied clinically. They were phenotypically homogeneous, having profound
      hearing impairment with very early onset, as shown by pure-tone audiometry and
      auditory brainstem responses. Magnetic resonance imaging and computed tomography
      did not reveal any inner ear malformation. Unexpectedly, transient evoked
      otoacoustic emissions (TEOAEs) were present, either bilaterally or unilaterally
      in 11 subjects. Altogether, clinical data of these subjects met the diagnostic
      criteria of auditory neuropathy. A total of 10 subjects had been successfully
      provided with cochlear implants. The results of our study indicate that genetic
      diagnosis of subjects with auditory neuropathy and profound hearing impairment
      should be directed to the otoferlin gene. Our data are of concern to universal
      screening programs which use TEOAEs as the first detection test for hearing
      impairment in newborns, since this technique may overlook a nonnegligible
      proportion of cases.

PMID- 14635105
TI  - Screening of 383 unrelated patients affected with Menkes disease and finding of
      57 gross deletions in ATP7A.
AB  - Menkes disease (MD) is an X-linked multisystemic lethal disorder of copper
      metabolism dominated by neurodegenerative symptoms and connective tissue
      disturbances. MD results from mutations in the ATP7A gene, which encodes a
      membrane-bound copper transporting P-type ATPase located in the trans-Golgi
      network. In this study we describe screening of 383 unrelated patients affected
      with Menkes disease for gross deletions in ATP7A gene and finding of 57 patients.
      The present data suggests that gross deletion of ATP7A is the disease-causing
      mutation in 14.9% of the Menkes disease patients. Except for a few cases, gross
      gene deletions result in the classical form of Menkes disease with death in early
      childhood.

PMID- 14635106
TI  - Bridging structural biology and genetics by computational methods: an
      investigation into how the R774C mutation in the AR gene can result in complete
      androgen insensitivity syndrome.
AB  - Recent structural studies of the ligand-binding domain (LBD) of the androgen
      receptor (AR) have raised more questions than answers, as most of the known
      pathogenic mutations of the AR gene causing androgen insensitivity syndrome (AIS)
      are not in the ligand-binding pocket. In this study, we have investigated one
      such pathogenic mutation, by examining details of its altered atomic structure
      using a computational technique of molecular dynamics (MD) simulations extended
      over 4 ns, effectively creating a 4D structural model. The mutation R774C, which
      is in the LBD of the AR gene, causes complete AIS (CAIS), producing ARs that have
      a unique thermolabile profile, being thermostable at 22 degrees C but
      thermolabile at 37 degrees C. We have therefore investigated this mutation by MD
      simulations at 293 K (20 degrees C), 300 K (27 degrees C), and 310 K (37 degrees
      C). The MD simulations indicate that: 1) the mutation causes local structural
      distortions, which result in changes in the shape of the ligand-binding pocket;
      2) the mutation alters the dynamic nature of the protein and results in a more
      diverse conformational distribution of the ligand-binding pocket; and 3) the
      effect of the mutation on AR structure could be largely reversed by lowering the
      temperature at which the MD simulations were conducted. These results therefore
      strongly support the biochemical data, e.g., the mutants' inability to form AR
      ligand complexes at 37 degrees C and its characteristic reversible
      thermolability, clearly indicating the value of such computational methods.

PMID- 14635107
TI  - CYP2D6 genotyping strategy based on gene copy number determination by TaqMan real
      time PCR.
AB  - The genetic polymorphism of the cytochrome P450 monooxygenase, CYP2D6, comprises
      at least 43 alleles giving rise to distinct drug metabolism phenotypes termed
      ultrarapid, extensive, intermediate, and poor metabolizers. As a consequence,
      drug side effects or lack of drug effect may occur if standard doses are applied.
      Genetic prediction of drug oxidation phenotype as a basis for dose selection
      requires analysis of single nucleotide polymorphisms and of alleles with
      duplicated or deleted genes. Here we developed a novel method to determine the
      CYP2D6 gene dose per genome. A TaqMan real-time PCR assay to specifically amplify
      genomic CYP2D6 was established by using a specific set of amplification primers
      and probe, located in exon 9, which effectively prevent amplification of CYP2D7
      and CYP2D8 pseudogenes. Quantitative CYP2D6 amplification data were normalized to
      albumin as an internal reference gene which was coamplified simultaneously in a
      single-tube biplex assay. The assay was validated with a selection of previously
      genotyped DNA samples containing none, one, two, or three CYP2D6 gene copies. The
      results were highly reproducible and closely matched the number of genes with no
      overlap between the groups. Analysis of DNA samples comprising all major alleles
      and genotypes revealed high sensitivity and specificity of the assay, as
      demonstrated by agreement of the determined gene dose with the presence of
      CYP2D6(*)2 x 2 (gene duplication) and CYP2D6(*) 5 (gene deletion) alleles. The
      predictability of the new strategy was systematically evaluated. The
      semiautomatic TaqMan assay allows high sample throughput and will be useful for
      pharmacogenetic studies and in the clinical setting.

PMID- 14635108
TI  - Fabry disease: characterization of alpha-galactosidase A double mutations and the
      D313Y plasma enzyme pseudodeficiency allele.
AB  - Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results
      from mutations in the gene encoding the lysosomal exoglycohydrolase, alpha
      galactosidase A (alpha-Gal A; GLA). In two unrelated classically affected males,
      two alpha-Gal A missense mutations were identified: R112C + D313Y (c.334C>T +
      c.937G>T) and C172G + D313Y (c.514T>G + c.937G>T). The D313Y lesion was
      previously identified in classically affected males as the single mutation [Eng
      et al., 1993] or in cis with another missense mutation, D313Y + G411D (c.937G>T +
      c.1232G>A) [Guffon et al., 1998]. To determine whether the D313Y mutation was a
      deleterious mutation or a coding region sequence variant, the frequency of D313Y
      in normal X-chromosomes, as well as its enzymatic activity and subcellular
      localization in COS-7 cells was determined. D313Y occurred in 0.45% of 883 normal
      X-chromosomes, while the R112C, C172G, and G411D missense mutations were not
      detected in over 500 normal X-chromosomes. Expression of D313Y in COS-7 cells
      resulted in approximately 60% of wild-type enzymatic activity and showed
      lysosomal localization, while R112C, C172G, G411D, and the double-mutated
      constructs had markedly reduced or no detectable activity and were all retained
      in the endoplasmic reticulum. The expressed D313Y enzyme was stable at lysosomal
      pH (pH 4.6), while at neutral pH (pH 7.4), it had decreased activity. A molecular
      homology model of human alpha-Gal A, based on the X-ray crystal structure of
      chicken alpha-galactosidase B (alpha-Gal B; alpha-N-acetylgalactosaminidase) was
      generated [Garman et al., 2002], which provided evidence that D313Y did not
      markedly disrupt the alpha-Gal A enzyme structure. Thus, D313Y is a rare exonic
      variant with about 60% of wild-type activity in vitro and reduced activity at
      neutral pH, resulting in low plasma alpha-Gal A activity.

PMID- 14635112
TI  - Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital
      glaucoma in France.
AB  - The CYP1B1 gene (GenBank: U56438), a member of the cytochrome P450 gene family,
      has been shown to be mutated in patients with primary congenital glaucoma (PCG),
      a rare but severely blinding form of glaucoma. Here, we have investigated CYP1B1
      mutations in 31 unrelated French PCG patients. Mutations were found in 15 (48%)
      patients. Six of these mutations were novel. One, g.3979delA, caused a frameshift
      followed by a stop codon at residue 59. Two mutations, g.4547C>T (p.Q248X) and
      g.8167C>T (p.R444X), created a stop codon. Three other mutations, g.4499G>C
      (p.G232R), g.8033T>G (p.I399S), (p.N423Y), induced a significant amino acid
      change. Seven patients, who were of French descent, were compound heterozygotes.
      Six patients, whose families came from North Africa or from Portugal, carried a
      homozygous mutation reflecting their geographic origin. Intriguingly, one
      mutation, p.E229K, was present in heterozygous state in two unrelated patients.
      All together, these findings demonstrate the major role and the diversity of
      CYP1B1 mutations in French PCG patients.

PMID- 14635113
TI  - A pathogenic glutamate-to-aspartate substitution (D296E) in the pyruvate
      dehydrogenase E1 subunit gene PDHA1.
AB  - In a patient with fatal neonatal lactic acidosis due to pyruvate dehydrogenase
      deficiency, the only potential mutation detected was c.888C>G in PDHA1, the gene
      for the E1alpha subunit of the complex. This would result in a substitution of
      glutamate for aspartate (D296E). Pathogenicity of this minor alteration in amino
      acid sequence was demonstrated by expression studies. By comparing the mutant
      sequence with the known structures of the E1 components of pyruvate dehydrogenase
      and the closely related branched chain alpha-ketoacid dehydrogenase, an
      explanation for the profound consequences of the mutation can be proposed.

PMID- 14635114
TI  - Diagnostics in patients with glutathione synthetase deficiency but without
      mutations in the exons of the GSS gene.
AB  - The synthesis of the ubiquitous tripeptide glutathione is impaired in patients
      with glutathione synthetase deficiency. The defect is inherited in an autosomal
      recessive manner, and the diagnosis is based on clinical, biochemical, and
      genetic criteria. In seven of our 30 index cases, however, no disease causing
      mutations could be identified in the coding exons or exon-intron boundaries of
      the glutathione synthetase gene GSS. These patients had severely decreased
      glutathione synthetase activities in lysates of cultured fibroblasts, and the
      levels of the enzyme were undetectable using a polyclonal antibody raised against
      human glutathione synthetase. RT-PCR mediated sequence analysis revealed
      previously not reported splice mutations in all patients. Thus, we conclude that
      in the investigation of patients with glutathione synthetase deficiency, and
      probably other genetic diseases as well, it might be time saving to initiate
      mutation analysis with sequencing of mRNA.

PMID- 14635115
TI  - Molecular analysis of the glyoxylate reductase (GRHPR) gene and description of
      mutations underlying primary hyperoxaluria type 2.
AB  - Primary hyperoxaluria type 2, an inherited autosomal recessive disorder of
      endogenous oxalate overproduction, is caused by mutations in the GRHPR gene
      encoding the glyoxylate/hydroxypyruvate reductase enzyme. The GRHPR genes from
      nineteen unrelated patients with PH2 were analysed for mutations using a
      combination of PCR-SSCP and sequence analysis of genomic and cDNA. Eleven
      mutations were identified, seven of which are novel. The mutations included five
      point mutations: c.84-2A>G, c.295C>T (R99X), c.494G>A (G165D), and c.904C>T
      (R302C) as well as six minor deletions: c.103delG, c.375delG, c.403_405+2
      delAAGT, c.540delT, c.608_609delCT and a more complex mutation in intron 1: c.84
      13_c.84-12del; c.84-8_c.84-5del. Aberrant transcripts were demonstrated in
      hepatic mRNA as a result of the c.403_405+2 delAAGT and c.84-2A>G mutations. In
      addition, a splice variant lacking 28 bp of exon 1 was expressed in a number of
      tissues but is of unknown function. Two polymorphisms, c.579A>G in exon 6 and a
      (CT)(n) microsatellite in intron 8 were identified. Expression studies showed
      that the G165D and R302C mutants had glyoxylate reductase activity 1.5 and 5.6%
      respectively of the wild type protein. Both mutant proteins were unstable on
      purification. Although there is wide expression of the GRHPR mRNA demonstrated by
      northern blot analysis, our study shows that GRHPR protein distribution is
      predominantly hepatic and concludes that PH2, like the related type 1 disease, is
      primarily a disorder affecting hepatic glyoxylate metabolism.

PMID- 14635116
TI  - Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected
      in cancer patients with 5-fluorouracil-related side effects.
AB  - Complete or partial loss of dihydropyrimidine dehydrogenase (DPD or DYPD)
      function has been described in cancer patients experiencing severe side effects
      upon administration of the fluoropyrimidine anticancer drug 5-fluorouracil (5
      FU). To investigate a genetic predisposition for 5-FU intolerance due to
      inherited DPD defects, we established a mutation detection assay based on
      denaturing HPLC. Analyzing four individuals with symptoms of 5-FU-related
      toxicity, we detected six distinct sequence variants in the dihydropyrimidine
      dehydrogenase gene (DPYD): one novel mutation, c.775A>G (K259E); four known
      missense mutations, c.85T>C (C29R), c.496A>G (M166V), c.1601G>A (S534N),
      c.1627A>G (I543V); and one silent mutation c.1896T>C affecting the codon for
      F632. One cancer patient possessing a total of four gene mutations resulting in
      four amino acid substitutions (C29R, M166V, S534N, I543V) displayed significantly
      reduced DPD activity. The rare combination of the highly conserved mutation sites
      M166V and S534N was additionally found in one of the other patients. DPD enzyme
      activity was low, but yet within normal range. The K259E mutation did not provoke
      a decrease in DPD function in a heterozygous individual. Based on the protein
      structure of crystalline pig DPD and the deduced homology models, we have
      additionally investigated the amino acid positions in their three-dimensional
      network which correspond to the five missense mutations discovered in the
      patients.

PMID- 14635117
TI  - Mutation screening of the C1 inhibitor gene among Hungarian patients with
      hereditary angioedema.
AB  - Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder
      characterized by episodic local subcutaneous and submucosal edema caused by the
      deficiency of activated C1 esterase inhibitor protein (C1-INH, type I (C1NH):
      reduced serum antigen level, type II: reduced activity and normal serum antigen
      level). The aim of the present study was to determine the disease-causing
      mutations in the C1INH gene (SERPING1) among Hungarian HAE-patients. The
      estimated number of affected HAE-families in Hungary is 40-50, out of which 26
      families (type I:23, type II:3) managed in a single center were enrolled in the
      current study. To detect large deletions/insertions, we used Southern-blotting
      analysis followed by real time PCR based gene dosage analysis. In the absence of
      large structural changes, we employed direct sequencing covering the whole coding
      region and splicing sites of the C1INH gene. Large deletions were detected in
      4/23 (17.4%) type I families. We found the g.16788C>T (p.Arg444Cys) mutation in
      each 3, type II HAE-families. In the remaining type I families, 13 previously
      unreported mutations (g.638G>A, g.2238C>T, g.2534_2535delCT, g.2579_2620del42,
      g.2533G>A, g.2695G>A, g.2696_2697insT, g.4467C>T, g.14224A>T, g.14107delA,
      g.16749_;16775dup, g.16810T>A, g.16885C>G) were detected in 16 families affecting
      primarily exon 3 (6/13) of the C1INH gene. In the 3 remaining families, known
      mutations were identified affecting primarily exon 8 (2/3).

PMID- 14635118
TI  - POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions.
AB  - The accumulation of multiple mitochondrial DNA (mtDNA) deletions in stable
      tissues is a distinctive feature of several autosomal disorders, characterized by
      Progressive External Ophthalmoplegia (PEO), ptosis, and proximal myopathy. At
      least three nuclear genes are responsible for these disorders: ANT1 and C10orf2
      cause autosomal dominant PEO, while mutations of DNA polymerase gammaA (POLG1 or
      POLG) gene on chromosome 15q25 causes both autosomal dominant and recessive forms
      of PEO. To investigate the contribution of these genes to the sporadic cases of
      PEO with multiple mtDNA deletions, we studied 31 mitochondrial myopathy patients
      without any family history for the disorder: 23 had PEO with myopathy, with or
      without the additional features of pigmentary retinopathy, ataxia, neurosensorial
      hypoacusia and diabetes mellitus, 7 presented isolated myopathy and one a
      peripheral neuropathy with ptosis. In all patients Southern blot of muscle DNA
      showed multiple mtDNA deletions; screening for ANT1 and C10ORF2 genes was
      negative. POLG analysis revealed mutations in eight patients; in six of them the
      mutations were allelic, while two patients were heterozygous. Five mutations were
      new, namely one stop codon (c.2407C>T/p.R709X) and four missense mutations
      (c.1085G>C/p.G268A; c.1967G>A/p.R562Q; c.2702G>C/p.R807P; c.3076C>T/p.H932W). A
      high degree of conservation was observed for all the new missense mutations. Only
      patients presenting PEO as part of their clinical phenotype had POLG mutations,
      in seven of them together with myopathic signs and in one with a sensori-motor
      peripheral neuropathy.

PMID- 14635119
TI  - NDP gene mutations in 14 French families with Norrie disease.
AB  - Norrie disease is a rare X-inked recessive condition characterized by congenital
      blindness and occasionally deafness and mental retardation in males. This disease
      has been ascribed to mutations in the NDP gene on chromosome Xp11.1. Previous
      investigations of the NDP gene have identified largely sixty disease-causing
      sequence variants. Here, we report on ten different NDP gene allelic variants in
      fourteen of a series of 21 families fulfilling inclusion criteria. Two
      alterations were intragenic deletions and eight were nucleotide substitutions or
      splicing variants, six of them being hitherto unreported, namely c.112C>T
      (p.Arg38Cys), c.129C>G (p.His43Gln), c.133G>A (p.Val45Met), c.268C>T
      (p.Arg90Cys), c.382T>C (p.Cys128Arg), c.23479-1G>C (unknown). No NDP gene
      sequence variant was found in seven of the 21 families. This observation raises
      the issue of misdiagnosis, phenocopies, or existence of other X-linked or
      autosomal genes, the mutations of which would mimic the Norrie disease phenotype.

PMID- 14635120
TI  - Conserved structural elements in glutathione transferase homologues encoded in
      the genome of Escherichia coli.
AB  - Multiple sequence alignments of the eight glutathione (GSH) transferase
      homologues encoded in the genome of Escherichia coli were used to define a
      consensus sequence for the proteins. The consensus sequence was analyzed in the
      context of the three-dimensional structure of the gst gene product (EGST)
      obtained from two different crystal forms of the enzyme. The enzyme consists of
      two domains. The N-terminal region (domain I) has a thioredoxin-like alpha/beta
      fold, while the C-terminal domain (domain II) is all alpha-helical. The majority
      of the consensus residues (12/17) reside in the N-terminal domain. Fifteen of the
      17 residues are involved in hydrophobic core interactions, turns, or
      electrostatic interactions between the two domains. The results suggest that all
      of the homologues retain a well-defined group of structural elements both in and
      between the N-terminal alpha/beta domain and the C-terminal domain. The
      conservation of two key residues for the recognition motif for the gamma-glutamyl
      portion of GSH indicates that the homologues may interact with GSH or GSH
      analogues such as glutathionylspermidine or alpha-amino acids. The genome context
      of two of the homologues forms the basis for a hypothesis that the b2989 and yibF
      gene products are involved in glutathionylspermidine and selenium biochemistry,
      respectively.

PMID- 14635121
TI  - Tolerance to the substitution of buried apolar residues by charged residues in
      the homologous protein structures.
AB  - Occurrence and accommodation of charged amino acid residues in proteins that are
      structurally equivalent to buried non-polar residues in homologues have been
      investigated. Using a dataset of 1,852 homologous pairs of crystal structures of
      proteins available at 2A or better resolution, 14,024 examples of apolar residues
      in the structurally conserved regions replaced by charged residues in homologues
      have been identified. Out of 2,530 cases of buried apolar residues, 1,677 of the
      equivalent charged residues in homologues are exposed and the rest of the charged
      residues are buried. These drastic substitutions are most often observed in
      homologous protein pairs with low sequence identity (<30%) and in large protein
      domains (>300 residues). Such buried charged residues in the large proteins are
      often located in the interface of sub-domains or in the interface of structural
      repeats, Beyond 7A of residue depth of buried apolar residues, or less than 4% of
      solvent accessibility, almost all the substituting charged residues are buried.
      It is also observed that acidic sidechains have higher preference to get buried
      than the positively charged residues. There is a preference for buried charged
      residues to get accommodated in the interior by forming hydrogen bonds with
      another sidechain than the main chain. The sidechains interacting with a buried
      charged residue are most often located in the structurally conserved regions of
      the alignment. About 50% of the observations involving hydrogen bond between
      buried charged sidechain and another sidechain correspond to salt bridges. Among
      the buried charged residues interacting with the main chain, positively charged
      sidechains form hydrogen bonds commonly with main chain carbonyls while the
      negatively charged residues are accommodated by hydrogen bonding with the main
      chain amides. These carbonyls and amides are usually located in the loops that
      are structurally variable among homologous proteins.

PMID- 14635122
TI  - Simplicial edge representation of protein structures and alpha contact potential
      with confidence measure.
AB  - Protein representation and potential function are two important ingredients for
      studying protein folding, equilibrium thermodynamics, and sequence design. We
      introduce a novel geometric representation of protein contact interactions using
      the edge simplices from the alpha shape of the protein structure. This
      representation can eliminate implausible neighbors that are not in physical
      contact, and can avoid spurious contact between two residues when a third residue
      is between them. We developed statistical alpha contact potential using an odds
      ratio model. A studentized bootstrap method was then introduced to assess the 95%
      confidence intervals for each of the 210 propensity parameters. We found, with
      confidence, that there is significant long-range propensity (>30 residues apart)
      for hydrophobic interactions. We tested alpha contact potential for native
      structure discrimination using several sets of decoy structures, and found that
      it often performs comparably with atom-based potentials requiring many more
      parameters. We also show that accurate geometric representation is important, and
      that alpha contact potential has better performance than potential defined by
      cutoff distance between geometric centers of side chains. Hierarchical clustering
      of alpha contact potentials reveals natural grouping of residues. To explore the
      relationship between shape and physicochemical representations, we tested the
      minimum alphabet size necessary for native structure discrimination. We found
      that there is no significant difference in performance of discrimination when
      alphabet size varies from 7 to 20, if geometry is represented accurately by alpha
      simplicial edges. This result suggests that the geometry of packing plays an
      important role, but the specific residue types are often interchangeable.

PMID- 14635123
TI  - Prediction of deleterious functional effects of amino acid mutations using a
      library of structure-based function descriptors.
AB  - An automated, active site-focused, computational method is described for use in
      predicting the effects of engineered amino acid mutations on enzyme catalytic
      activity. The method uses structure-based function descriptors (Fuzzy Functional
      Forms trade mark or FFFs trade mark ) to automatically identify enzyme functional
      sites in proteins. Three-dimensional sequence profiles are created from the
      surrounding active site structure. The computationally derived active site
      profile is used to analyze the effect of each amino acid change by defining three
      key features: proximity of the change to the active site, degree of amino acid
      conservation at the position in related proteins, and compatibility of the change
      with residues observed at that position in similar proteins. The features were
      analyzed using a data set of individual amino acid mutations occurring at 128
      residue positions in 14 different enzymes. The results show that changes at key
      active site residues and at highly conserved positions are likely to have
      deleterious effects on the catalytic activity, and that non-conservative
      mutations at highly conserved residues are even more likely to be deleterious.
      Interestingly, the study revealed that amino acid substitutions at residues in
      close contact with the key active site residues are not more likely to have
      deleterious effects than mutations more distant from the active site. Utilization
      of the FFF-derived structural information yields a prediction method that is
      accurate in 79-83% of the test cases. The success of this method across all six
      EC classes suggests that it can be used generally to predict the effects of
      mutations and nsSNPs for enzymes. Future applications of the approach include
      automated, large-scale identification of deleterious nsSNPs in clinical
      populations and in large sets of disease-associated nsSNPs, and identification of
      deleterious nsSNPs in drug targets and drug metabolizing enzymes.

PMID- 14635124
TI  - Construction of molecular assemblies via docking: modeling of tetramers with D2
      symmetry.
AB  - Comparative modeling methods are commonly used to construct models of homologous
      proteins or oligomers. However, comparative modeling may be inapplicable when the
      number of subunits in a modeled oligomer is different than in the modeling
      template. Thus, a dimer cannot be a template for a tetramer because a new monomer
      monomer interface must be predicted. We present in this study a new prediction
      approach, which combines protein-protein docking with either of two tetramer
      forming algorithms designed to predict the structures of tetramers with D2
      symmetry. Both algorithms impose symmetry constraints. However, one of them
      requires identification of two of the C2 dimers within the tetramer in the
      docking step, whereas the other, less demanding algorithm, requires
      identification of only one such dimer. Starting from the structure of one
      subunit, the procedures successfully reconstructed 16 known D2 tetramers, which
      crystallize with either a monomer, a dimer or a tetramer in the asymmetric unit.
      In some cases we obtained clusters of native-like tetramers that differ in the
      relative rotation of the two identical dimers within the tetramer. The predicted
      structural pliability for concanavalin-A, phosphofructokinase, and fructose-1,6
      bisphosphatase agrees semiquantitatively with the observed differences between
      the several experimental structures of these tetramers. Hence, our procedure
      identifies a structural soft-mode that allows regulation via relative rigid-body
      movements of the dimers within these tetramers. The algorithm also predicted
      three nearly correct tetramers from model structures of single subunits, which
      were constructed by comparative modeling from subunits of homologous tetrameric,
      dimeric, or hexameric systems.

PMID- 14635125
TI  - Tomato pectin methylesterase: modeling, fluorescence, and inhibitor interaction
      studies-comparison with the bacterial (Erwinia chrysanthemi) enzyme.
AB  - The molecular model of Lycopersicon esculentum (tomato) pectin methylesterase
      (PME) was built by using the X-ray crystal structure of PME from the
      phytopathogenic bacterium Erwinia chrysanthemi as a template. The overall
      structure and the position of catalytically important residues (Asp132, Asp 153,
      and Arg 221, located at the bottom of the active site cleft) are conserved.
      Instead, loop regions forming the walls of the catalytic site are much shorter
      and form a less deep cleft, as already revealed by the carrot PME crystal
      structure. The protein inhibitor of pectin methylesterase (PMEI) isolated from
      kiwi fruit binds tomato PME with high affinity. Conversely, no complex formation
      between the inhibitor and PME from E. chrysanthemi is observed, and the activity
      of this enzyme is unaffected by the presence of the inhibitor. Fluorescence
      quenching experiments on tomato PME and on PME-PMEI complex suggest that
      tryptophanyl residues present in the active site region are involved in the
      interaction and that the inhibitor interacts with plant PME at the level of the
      active site. We also suggest that the more open active site cleft of tomato PME
      allows the interaction with the inhibitor. Conversely, the narrow and deep cleft
      of the active site of E. chrysanthemi PME hinders this interaction. The pH
      dependent changes in fluorescence emission intensity observed in tomato PME could
      arise as the result of protonation of an Asp residue with unusually high pKa,
      thus supporting the hypothesis that Asp132 acts as acid/base in the catalytic
      cycle.

PMID- 14635126
TI  - Combination of scoring functions improves discrimination in protein-protein
      docking.
AB  - Two structure-based potentials are used for both filtering (i.e., selecting a
      subset of conformations generated by rigid-body docking), and rescoring and
      ranking the selected conformations. ACP (atomic contact potential) is an atom
      level extension of the Miyazawa-Jernigan potential parameterized on protein
      structures, whereas RPScore (residue pair potential score) is a residue-level
      potential, based on interactions in protein-protein complexes. These potentials
      are combined with other energy terms and applied to 13 sets of protein decoys, as
      well as to the results of docking 10 pairs of unbound proteins. For both
      potentials, the ability to discriminate between near-native and non-native docked
      structures is substantially improved by refining the structures and by adding a
      van der Waals energy term. It is observed that ACP and RPScore complement each
      other in a number of ways (e.g., although RPScore yields more hits than ACP,
      mainly as a result of its better performance for charged complexes, ACP usually
      ranks the near-native complexes better). As a general solution to the protein
      docking problem, we have found that the best discrimination strategies combine
      either an RPScore filter with an ACP-based scoring function, or an ACP-based
      filter with an RPScore-based scoring function. Thus, ACP and RPScore capture
      complementary structural information, and combining them in a multistage
      postprocessing protocol provides substantially better discrimination than the use
      of the same potential for both filtering and ranking the docked conformations.

PMID- 14635127
TI  - Natively unfolded C-terminal domain of caldesmon remains substantially
      unstructured after the effective binding to calmodulin.
AB  - The structure of C-terminal domain (CaD136, C-terminal residues 636-771) of
      chicken gizzard caldesmon has been analyzed by a variety of physico-chemical
      methods. We are showing here that CaD136 does not have globular structure, has
      low secondary structure content, is essentially noncompact, as it follows from
      high R(g) and R(S) values, and is characterized by the absence of distinct heat
      absorption peaks, i.e. it belongs to the family of natively unfolded (or
      intrinsically unstructured) proteins. Surprisingly, effective binding of single
      calmodulin molecule (K(d) = 1.4 +/- 0.2 microM) leads only to a very moderate
      folding of this protein and CaD136 remains substantially unfolded within its
      tight complex with calmodulin. The biological significance of these observations
      is discussed.

PMID- 14635128
TI  - Thermodynamic effects of replacements of Pro residues in helix interiors of
      maltose-binding protein.
AB  - Introduction of Pro residues into helix interiors results in protein
      destabilization. It is currently unclear if the converse substitution (i.e.,
      replacement of Pro residues that naturally occur in helix interiors would be
      stabilizing). Maltose-binding protein is a large 370-amino acid protein that
      contains 21 Pro residues. Of these, three nonconserved residues (P48, P133, and
      P159) occur at helix interiors. Each of the residues was replaced with Ala and
      Ser. Stabilities were characterized by differential scanning calorimetry (DSC) as
      a function of pH and by isothermal urea denaturation studies as a function of
      temperature. The P48S and P48A mutants were found to be marginally more stable
      than the wild-type protein. In the pH range of 5-9, there is an average increase
      in T(m) values of P48A and P48S of 0.4 degrees C and 0.2 degrees C, respectively,
      relative to the wild-type protein. The other mutants are less stable than the
      wild type. Analysis of the effects of such Pro substitutions in MBP and in three
      other proteins studied to date suggests that substitutions are more likely to be
      stabilizing if the carbonyl group i-3 or i-4 to the mutation site is not hydrogen
      bonded in the wild-type protein.

PMID- 14635129
TI  - Analysis of protein structures reveals regions of rare backbone conformation at
      functional sites.
AB  - Regions of rare conformation were located in 300 protein crystal structures
      representing seven major protein folds. A distance matrix algorithm was used to
      search rapidly for 9-residue fragments of rare backbone conformation using a
      comparison to a relational database of encoded fragments derived from the
      database of nonredundant structures. Rare fragments were found in 61% of the
      analyzed protein structures. Detailed analysis was performed for 78 proteins of
      different folds. The rare fragments were located near functional sites in 72% of
      the protein structures. The rare fragments often formed parts of ligand-binding
      sites (59%), protein-protein interfaces (8%), and domain-domain contacts (5%). Of
      the remaining structures, 5% had a high average B-factor or high local B-factors.
      Statistical analysis suggests that the association between ligands and rare
      regions does not occur by chance alone. The present study is likely to
      underestimate the number of functional sites, because not all analyzed protein
      structures contained a ligand. The results suggest that rapid searches for
      regions with rare local backbone conformations can assist in prediction of
      functional sites in novel proteins.

PMID- 14635130
TI  - Hydrophobic moments of tertiary protein structures.
AB  - The helical hydrophobic moment is a measure of the amphiphilicity of a segment of
      protein secondary structure. Such measure yields information of potential
      relevance for issues relating to cell surface binding and secondary structure
      function. The present article describes a global analog of the helical
      hydrophobic moment. The global moment provides a concise measure of the degree
      and direction of the amphiphilicity or hydrophobic imbalance across the entire
      protein tertiary structure. Therefore, this measure is a succinct representation
      of the spatial organization of residue hydrophobicity for each protein. With this
      measure, a simple comparison of the hydrophobic imbalance or segregation of
      different protein structures can be made. For example, two structures having the
      same fold and close in root-mean-square deviation may exhibit very different
      overall hydrophobic organization. Such difference is classified simply by the
      global moment. Furthermore, the direction of the global moment may point to
      regions of functional interest. Certain formal issues in the development of such
      moment are described, and a number of applications to particular protein
      structures are discussed.

PMID- 14635131
TI  - A reduced protein model with accurate native-structure identification ability.
AB  - A protein model that is simple enough to be used in protein-folding simulations
      but accurate enough to identify a protein native fold is described. Its geometry
      consists of describing the residues by one, two, or three pseudoatoms, depending
      on the residue size. Its energy is given by a pairwise, knowledge-based potential
      obtained for all the pseudoatoms as a function of their relative distance. The
      pseudoatomic potential is also a function of the primary chain separation and
      residue order. The model is tested by gapless threading on a large,
      representative set of known protein and decoy structures obtained from the
      "Decoys 'R' Us" database. It is also tested by threading on gapped decoys
      generated for proteins with many homologs. The gapless threading tests show near
      98% native-structure recognition as the lowest energy structure and almost 100%
      as one of the three lowest energy structures for over 2200 test proteins. In
      decoy threading tests, the model recognized the majority of the native
      structures. It is also able to recognize native structures among gapped decoys,
      in spite of close structural similarities. The results indicate that the
      pseudoatomic model has native recognition ability similar to comparable atomic
      based models but much better than equivalent residue-based models.

PMID- 14635132
TI  - The C-terminal module of Chi1 from Aeromonas caviae CB101 has a function in
      substrate binding and hydrolysis.
AB  - The chitinase gene chi1 of Aeromonas caviae CB101 encodes an 865-amino-acid
      protein (with signal peptide) composed of four domains named from the N-terminal
      as an all-beta-sheet domain ChiN, a triosephosphate isomerase (TIM) catalytic
      domain, a function-unknown A region, and a putative chitin-binding domain (ChBD)
      composed of two repeated sequences. The N-terminal 563-amino-acid segment of Chi1
      (Chi1DeltaADeltaChBD) shares 74% identity with ChiA of Serratia marcescens. By
      the homology modeling method, the three-dimensional (3D) structure of
      Chi1DeltaADeltaChBD was constructed. It fit the structure of ChiA very well. To
      understand fully the function of the C-terminal module of Chi1 (from 564 to 865
      amino acids), two different C-terminal truncates, Chi1DeltaChBD and
      Chi1DeltaADeltaChBD, were constructed, based on polymerase chain reaction (PCR).
      Comparison studies of the substrate binding, hydrolysis capacity, and specificity
      among Chi1 and its two truncates showed that the C-terminal putative ChBD
      contributed to the insoluble substrate-protein binding and hydrolysis; the A
      region did not have any function in the insoluble substrate-protein binding, but
      it did have a role in the chitin hydrolysis: Deletion of the A region caused the
      enzyme to lose 30-40% of its activity toward amorphous colloidal chitin and
      soluble chitin, and around 50% toward p-nitrophenyl (pNP)-chitobiose pNP
      chitotriose, and its activity toward low-molecular-weight chitooligomers
      (GlcNAc)3-6 also dropped, as shown by analysis of its digestion processes. This
      is the first clear demonstration that a domain or segment without a function in
      insoluble substrate-chitinase binding has a role in the digestion of a broad
      range of chitin substrates, including low-molecular-weight chitin oligomers. The
      reaction mode of Chi1 is also described and discussed.

PMID- 14635133
TI  - Better prediction of sub-cellular localization by combining evolutionary and
      structural information.
AB  - The native sub-cellular compartment of a protein is one aspect of its function.
      Thus, predicting localization is an important step toward predicting function.
      Short zip code-like sequence fragments regulate some of the shuttling between
      compartments. Cataloguing and predicting such motifs is the most accurate means
      of determining localization in silico. However, only few motifs are currently
      known, and not all the trafficking appears regulated in this way. The amino acid
      composition of a protein correlates with its localization. All general prediction
      methods employed this observation. Here, we explored the evolutionary information
      contained in multiple alignments and aspects of protein structure to predict
      localization in absence of homology and targeting motifs. Our final system
      combined statistical rules and a variety of neural networks to achieve an overall
      four-state accuracy above 65%, a significant improvement over systems using only
      composition. The system was at its best for extra-cellular and nuclear proteins;
      it was significantly less accurate than TargetP for mitochondrial proteins.
      Interestingly, all methods that were developed on SWISS-PROT sequences failed
      grossly when fed with sequences from proteins of known structures taken from PDB.
      We therefore developed two separate systems: one for proteins of known structure
      and one for proteins of unknown structure. Finally, we applied the PDB-based
      system along with homology-based inferences and automatic text analysis to
      annotate all eukaryotic proteins in the PDB
      (http://cubic.bioc.columbia.edu/db/LOC3D). We imagine that this pilot method
      certainly in combination with similar tools-may be valuable target selection in
      structural genomics.

PMID- 14635134
TI  - Rational proteomics I. Fingerprint identification and cofactor specificity in the
      short-chain oxidoreductase (SCOR) enzyme family.
AB  - The short-chain oxidoreductase (SCOR) family of enzymes includes over 2000
      members identified in sequenced genomes. Of these enzymes, approximately 200 have
      been characterized functionally, and the three-dimensional crystal structures of
      approximately 40 have been reported. Since some SCOR enzymes are involved in
      hypertension, diabetes, breast cancer, and polycystic kidney disease, it is
      important to characterize the other members of the family for which the
      biological functions are currently unknown. Although the SCOR family appears to
      have only a single fully conserved residue, it was possible, using bioinformatics
      methods, to determine characteristic fingerprints composed of 30-40 residues that
      are conserved at the 70% or greater level in SCOR subgroups. These fingerprints
      permit reliable prediction of several important structure-function features
      including NAD/NADP cofactor preference. For example, the correlation of aspartate
      or arginine residues with NAD or NADP binding, respectively, predicts the
      cofactor preference of more than 70% of the SCOR proteins with unknown function.
      The analysis of conserved residues surrounding the cofactor has revealed the
      presence of previously undetected CH em leader O hydrogen bonds in the majority
      of the SCOR crystal structures, predicts the presence of similar hydrogen bonds
      in 90% of the SCOR proteins of unknown function, and suggests that these hydrogen
      bonds may play a critical role in the catalytic functions of these enzymes.

PMID- 14635135
TI  - Structural genomics of Caenorhabditis elegans: structure of dihydropteridine
      reductase.

PMID- 14635136
TI  - Structural genomics of caenorhabditis elegans: crystal structure of calmodulin.

PMID- 14635137
TI  - Structure of the bacillus subtilis YYCN protein: a putative N-acetyltransferase.

PMID- 14635138
TI  - Introduction to the aging of primary lymphoid organs: cellular or homeostatic
      failure?

PMID- 14635139
TI  - Evolution of the thymus size in response to physiological and random events
      throughout life.
AB  - During embryogenesis and in the early stages of life, the thymus is a crucial
      organ for the generation of the T cell repertoire. T cells are generated from
      hematopoietic stem cells already differentiated to precursor T cells in the bone
      marrow. These cells enter the thymus guided by chemotactic factors secreted by
      this organ. The complex maturation process takes place that ensures self
      tolerance and homeostasis. Thymocytes that show autoreactivity do not leave the
      thymus, but rather die by apoptosis. The final percentage of mature T cells that
      survive to migrate from the thymus to the periphery is very low: at most 5%,
      under optimal conditions. The highest migration occurs in childhood and
      adulthood, at least in mice and humans; however, it declines throughout life and
      is minimal in the elderly. Under normal circumstances, the thymus commences
      involution soon after birth, and this involution correlates with the capacity to
      export mature T cells to the periphery. Hormones, cytokines, and
      neurotransmitters all play a role in this age-associated process, but the reasons
      for and mechanisms of this involution remain unknown. Apart from physiological
      conditions that change throughout life and govern age-related thymus evolution,
      random states and events provoked by intrinsic or extrinsic factors can induce
      either thymus involution, as in reversible transient thymic hypoplasias, or
      thymic hyperplasias. The age-associated involution, unlike transient involutions,
      follows a regular pattern for all individuals, though there are clear differences
      between the sexes. Nevertheless, even the age-associated involution seems to be
      reversible, raising the possibility of therapeutic strategies aimed at enhancing
      thymus function in the elderly.

PMID- 14635140
TI  - Aging of the vertebrate immune system.
AB  - We have summarized current knowledge on the aging of the immune system in three
      vertebrate groups: fish, amphibians and birds. Available data are few due to
      difficulties in studying ageing in natural populations and in accurately
      determining age. In all vertebrates, the most obvious evidence of the senescence
      of lymphoid tissue is the involution of thymus, which courses with decreased
      numbers of thymocytes, and loss of the histological organization of gland. On the
      other hand, there is little information on aged secondary lymphoid organs.
      Possible influence of the endocrine system in the changes observed in aged
      lymphoid organs is also discussed.

PMID- 14635141
TI  - Age-related changes in the avian primary lymphoid organs (thymus and bursa of
      Fabricius).
AB  - The avian primary lymphoid organs, the thymus and the bursa of Fabricius, undergo
      age-dependent changes leading in some cases to the complete atrophy of the organ.
      Nevertheless, the timetable of the involutive process as well as the consequences
      in the structure and functionality of the organs vary largely in the time frame
      and structural changes among species. On the other hand, and in contrast with the
      large body of literature reporting the structural and functional changes in
      mammalian primary lymphoid organs, the age-dependent changes in avian thymus and
      bursa of Fabricius are scarce, fragmentary, and heterogeneous. This article
      reviews the current literature on this topic, and focuses primarily on the
      involution of the bursa of Fabricius.

PMID- 14635142
TI  - Thymic epithelial cells in age-dependent involution.
AB  - Aging involves morphological and functional alterations within the
      microenvironment of the thymus where heterogenous populations of thymic
      epithelial cells (TEC) play the main roles. The studies performed to date on
      thymic involution signalize a disturbed interaction between individual thymic
      compartments that disrupt thymocyte-TEC interactions and, as a sequele, disturb
      differentiation of both TEC and thymocytes. The process of aging affects the
      various subsets of TEC at different periods of life. Changes in different subsets
      of TEC are documented on the basis of their phenotypical characteristics,
      involving morphological analysis and immunocytochemistry. The character and
      kinetics of changes in TEC are typical for individual subsets and probably sex
      dependent. In the course of life, the involutionary changes, expressed by
      disorganised thymic structure and function, are accompanied by changes in
      medullary TEC, manifested by alterations in the differentiation process of the
      cells. In parallel, at the same stage of individual life, the aging process
      induces increased proliferative and secretory activity of subseptal TEC, which
      seem to functionally replace medullary TEC. Structural and phenotypic
      modifications of TEC are locally controlled by complex sets of different factors
      and seem to represent a morphological adaptation of the gland to the process of
      aging. Microsc. Res. Tech. 62:488-500, 2003.

PMID- 14635143
TI  - Age-dependent changes in thymic macrophages and dendritic cells.
AB  - Aging is characterized by the decline and deregulation of several physiological
      systems, especially the immune system. The involution of the thymus gland has
      been identified as one of the key events that precedes the age-related decline in
      immune function. Whereas the decrease in thymocyte numbers and in the thymic
      output during thymus atrophy has been analyzed by various authors, very little
      information is available about the age-associated modifications in thymic
      macrophages and dendritic cells. Here we present evidence that these thymic
      stromal cell components are only slightly affected by age.

PMID- 14635144
TI  - Age-related changes in the function of T cells.
AB  - At the start of the last century in the United Kingdom, only 24% of the 587,830
      deaths registered were of individuals over 65, but by the end of the century
      these figures had changed markedly. Of the 558,052 deaths in 1997, 84% were in
      the population over 65. This "right shift" in the survival curve is projected to
      continue. The UK Government Actuary's Department forecast that by 2020, 11.75
      million people (19% of the population) will be over 65 rising to 15.1 million
      people (25% of the population) by 2040. Older members of society show infections
      of the urinary tract, respiratory tract, skin, soft tissue or intra-abdominal
      region, infectious endocarditis, bacterial meningitis, tuberculosis, and herpes
      zoster, at a higher incidence than among younger adults. Moreover, mortality
      rates for these diseases are often 2-3 times higher among elderly patients than
      younger individuals with the same disease. The higher morbidity and mortality
      from these infections, plus the increased prevalence of specific cancers and
      certain autoimmune diseases point to an immune system deteriorating with age. At
      the core of the immune system are the T cells and this review analyses possible
      causes for the changes in T cell function that may account for the deterioration
      of the immune system. Any intervention to reverse the decline in the immune
      system must have a rational basis built on a hypothesis-driven inquiry, and one
      such intervention process is presented here.

PMID- 14635145
TI  - Involvement of growth factors in thymic involution.
AB  - The thymus undergoes an age-dependent degenerative process which is mainly
      characterized by a progressive loss of lymphoid tissue. Thymic involution is
      particularly important in relation to immunosenescence and its various associated
      diseases; this fact has prompted many studies aimed at understanding the causes
      and mechanisms of thymic degeneration which may, ultimately, lead to the
      possibility of manipulating it. In this sense, one of the aspects which has
      deserved most attention is the thymic microenvironment, and more precisely, the
      many growth factors to which the cells present in the organ are exposed. Thus,
      the levels of several of such factors have been reported to undergo age-dependent
      changes in the thymus, which may point at an influence on the regression of the
      organ. In this article we consider which growth factors and growth factor
      receptors occur in the vertebrate thymus. Then, focusing on those whose
      influences are better documented, i.e., neurotrophins, cytokines and IGFs, we
      discuss their potential role in the organ and the possibility of their being
      involved in thymic involution.

PMID- 14635146
TI  - Apoptosis in primary lymphoid organs with aging.
AB  - Age-associated changes in the immune system are responsible for an increased
      likelihood of infection, autoimmune diseases, and cancer in the elderly.
      Immunosenescence is characterized by reduced levels of the peripheral naive T
      cell pool derived from thymus and the loss of immature B lineage cells in the
      bone marrow. Primary lymphoid organs, i.e., bone marrow and thymus, exhibit a
      loss of cellularity with age, which is especially dramatic in the thymus. A
      summary of major changes associated with aging in primary lymphoid organs is
      described in this article. The participation of apoptosis in cell loss in the
      immune system, a change associated with age, as well as a description of
      molecular machinery involved, is presented. Finally, the involvement of different
      hormonal and non-hormonal agents in counteracting apoptosis in thymus and bone
      marrow during aging is explained. Here, we underlie the important role of
      glucocorticoids as immunodepressors and melatonin as an immunostimulatory agent.

PMID- 14635147
TI  - MRI for the diagnosis of pulmonary embolism.
AB  - Pulmonary embolism (PE) is one of the most frequently encountered clinical
      emergencies. The diagnosis often involves multiple diagnostic tests, which need
      to be carried out rapidly to assist in the safe management of the patient. Recent
      strides in computed tomography (CT) have made big improvements in patient
      management and efficiency of diagnostic imaging. This review article describes
      the developments in magnetic resonance (MR) techniques for the diagnosis of acute
      PE. Techniques include MR angiography (MRA) and thrombus imaging for direct clot
      visualization, perfusion MR, and combined perfusion-ventilation MR. As will be
      demonstrated, some of these techniques are now entering the clinical arena, and
      it is anticipated that MR imaging (MRI) will have an increasing role in the
      initial diagnosis and follow-up of patients with acute PE.

PMID- 14635148
TI  - DTI-based three-dimensional tractography detects differences in the pyramidal
      tracts of infants and children with congenital hemiparesis.
AB  - PURPOSE: To test the hypothesis that there is greater asymmetry in diffusion
      properties between right and left pyramidal tracts in patients with congenital
      hemiparesis than in patients with normal motor function. MATERIALS AND METHODS:
      Four congenitally hemiparetic patients and four age-matched controls underwent
      magnetic resonance diffusion tensor imaging (DTI)-based three-dimensional
      tractography of the pyramidal tracts. Relative anisotropy, individual
      eigenvalues, and directionally averaged apparent diffusion coefficient were
      measured and degree of asymmetry was calculated. RESULTS: Compared with age
      matched controls, congenitally hemiparetic patients had greater asymmetry in all
      measured diffusion properties. The asymmetry was characterized primarily by lower
      anisotropy, lower parallel diffusion, higher transverse diffusion, and slightly
      higher mean diffusivity in the pyramidal tract contralateral to the hemiparesis
      (i.e., affected pyramidal tract) compared with the unaffected pyramidal tract.
      CONCLUSIONS: There appears to be greater diffusion asymmetry between the
      pyramidal tracts in congenitally hemiparetic patients compared to controls. These
      differences suggest that there are alterations in the microstructure of the
      pyramidal tract that controls the motor function of the hemiparetic side. Our
      results suggest that DTI-based three-dimensional tractography is potentially
      useful in the assessment of motor dysfunction in infants and children with
      congenital hemiparesis.

PMID- 14635149
TI  - Precision of the CASL-perfusion MRI technique for the measurement of cerebral
      blood flow in whole brain and vascular territories.
AB  - PURPOSE: To analyze the precision of cerebral blood flow (CBF) measurements made
      with continuous arterial spin labeling(CASL) perfusion magnetic resonance imaging
      (MRI) over experimentally relevant intervals. MATERIALS AND METHODS: CASL
      perfusion MRI measurements of CBF on a 1.5-T GE Signa magnet were repeated in
      young healthy male and female subjects at one hour and one week. Precision of the
      measurement was evaluated at both time intervals. RESULTS: CASL perfusion MRI
      measurements of CBF yielded within-subject coefficients of variation (wsCV) of
      5.8% for global and 13% for individual vascular regions when measurements were
      repeated within one hour. Differences in these values represent the error in post
      processing. Global and regional CBF measurements over one week yielded wsCVs of
      13% and 14%, respectively. At one week, error secondary to physiologic
      variability affected global and regional measurements to the same degree and
      masked the software post-processing error seen at one hour. The magnitude of the
      difference in repeated measures correlated with the magnitude of the measurement.
      CONCLUSION: CASL perfusion MRI CBF measurements are accurate and precise.
      Variability over longer periods of time appears attributable to physiologic
      factors. Repeatability of the CASL measurement is sensitive to the magnitude of
      the measurement. This should be taken into account when studies requiring
      repeated measures involve subjects with significant variability in CBF.

PMID- 14635150
TI  - Multislice T1 relaxation time measurements in the brain using IR-EPI:
      reproducibility, normal values, and histogram analysis in patients with multiple
      sclerosis.
AB  - PURPOSE: To perform T(1) measurements using inversion recovery (IR) echoplanar
      imaging (EPI) to evaluate reproducibility, normal values, and T(1) histogram
      analysis as a measure of disease progression in multiple sclerosis (MS) patients.
      MATERIALS AND METHODS: Multislice IR-EPI was performed in 10 controls and 36 MS
      patients. Region-of-interest (ROI) and T(1) histogram analysis were performed on
      T(1) maps and compared to hypointense T(1) lesions and brain atrophy in MS
      patients. RESULTS: Coefficient of variation (COV) varied from 1.6% to 4.9%.
      Callosal normal (appearing) white matter (N(A)WM) showed the lowest and cortical
      gray matter the highest T(1) values. T(1) histogram analysis in controls showed a
      sharp WM peak centered on a T(1) value of 729 msec (range = 679-765) with
      extension into a shoulder of higher T(1) values. In MS patients, a shift toward
      higher T(1) values (mean = 788 msec, range = 700-957) with a lower relative peak
      amplitude was present, predominantly resulting from T(1) prolongation in NAWM.
      T(1) histogram parameters strongly related to hypointense T(1) lesion volume and
      brain atrophy in MS patients. CONCLUSIONS: IR-EPI provides a reproducible method
      to obtain T(1) values in the brain. Regional variation in T(1) values is present
      in N(A)WM of volunteers and MS patients. Since T(1) histogram parameters reflect
      changes in NAWM and correlate with conventional measures of disease burden in MS
      patients, T(1) histogram analysis may provide a global measure of disease
      progression in MS.

PMID- 14635151
TI  - The evolution of the apparent diffusion coefficient in the pediatric brain at low
      and high diffusion weightings.
AB  - PURPOSE: To evaluate the evolution of the apparent diffusion coefficient (ADC)
      with age for different degrees of diffusion weighting using a clinically feasible
      approach. MATERIALS AND METHODS: Data was acquired using separate scans with b
      values in the range typically used for clinical studies (100-900 seconds/mm(2))
      and higher b values (1800-3000 seconds/mm(2)). The ADC was calculated for each of
      the data sets by fitting the data to a monoexponential function. RESULTS: The
      results from 50 children aged three years and less showed some deviations from
      literature values derived using a full biexponential fit, with these differences
      reflecting the approximations inherent in this approach. The values obtained with
      this technique appear to be reproducible but the resulting "institutional values"
      are comparable to those from other centers only if identical measurement criteria
      are used. CONCLUSION: A significant decline in both components of the ADC during
      the first few months of life was observed; in addition, the attenuated slow ADC
      values seen in adult white matter were only present at birth in early myelinating
      regions. The subsequent development of the slow ADC in white matter suggests that
      it is associated with myelination or processes associated with axonal
      development.

PMID- 14635152
TI  - Pyruvate: an in vivo marker of cestodal infestation of the human brain on proton
      MR spectroscopy.
AB  - PURPOSE: To study intracranial cestodal cysts using in vivo proton magnetic
      resonance spectroscopy ((1)H MRS) in an effort to identify metabolite(s) that may
      help in recognizing the parasitic etiology and, perhaps, viability of such
      tapeworm cysts. Cestodal infestations of the human central nervous system (CNS)
      cysticercosis and hydatidosis-are not rare. Identification of a scolex is
      considered diagnostic of cysticercosis on imaging. In its absence, however, the
      features are non-specific. MATERIALS AND METHODS: Three patients with
      intracranial hydatid cysts and 13 patients with intracranial cysticercal cysts
      (four intraventricular, seven parenchymal, and two subarachnoid racemose cysts)
      were studied on a 1.5-T MR system. In vivo (1)H MRS was performed by multivoxel
      two-dimensional hybrid chemical shift imaging technique (TE = 135 msec). In vitro
      (1)H NMR and mass spectroscopy (matrix assisted laser desorption/ionization
      [MALDI]) were performed on excised cysticercal and hydatid cyst fluid. MALDI
      spectra for pyruvate and succinate were also obtained. RESULTS: Alanine,
      pyruvate, and acetate were seen in all the three hydatid cysts. Lactate was seen
      in racemose cysticercal cysts. A large resonance at 2.4 ppm, confirmed as
      pyruvate at mass spectroscopy, was seen in 13 cestodal cysts. Pyruvate was not
      seen in one each of racemose, intraventricular, and parenchymal cysticercal
      cysts. CONCLUSION: Pyruvate is the predominant metabolite in cestodal cysts
      infesting the human CNS. It may be a marker of parasitic etiology and perhaps
      that of viability of such intracranial cysts.

PMID- 14635153
TI  - Using an adaptive semiautomated self-evaluated registration technique to analyze
      MRI data for myocardial perfusion assessment.
AB  - PURPOSE: To validate the adaptive semiautomated self-evaluated registration
      technique (ASSERT) followed by factor analysis of medical image sequence (FAMIS)
      for analyzing myocardial perfusion using magnetic resonance imaging (MRI) images.
      MATERIALS AND METHODS: Eleven patients having a significant stenosis of at least
      one coronary artery detected by coronarography were examined by thallium
      tomoscintigraphy and perfusion MRI (first-pass of Gd-DTPA-BMA) at rest and under
      pharmacologic stress. The MRI images were analyzed by ASSERT to correct for rigid
      motion in the acquisition plane and to reject those images that were severely
      deformed or acquired outside the slice plane. The images thus obtained were
      analyzed by FAMIS. The resulting factor images representing myocardial perfusion
      were read to identify the ischemic territories corresponding to left anterior
      descending coronary arteries and right coronary arteries. RESULTS: ASSERT allowed
      automatic correction for motion and the exclusion of images that could not be
      registered. The ischemic territories, identified from the factor images of the
      myocardium, agreed with those identified by coronarography and tomoscintigraphy
      for 20 of the 22 territories. CONCLUSION: The results demonstrate the feasibility
      of analyzing myocardial perfusion using MRI acquisition and treating the
      resulting images by ASSERT and FAMIS. Extending this method to multislice
      examinations will enable evaluation of the perfusion of the whole myocardium.

PMID- 14635154
TI  - Fast, high-resolution in vivo cine magnetic resonance imaging in normal and
      failing mouse hearts on a vertical 11.7 T system.
AB  - PURPOSE: To establish fast, high-resolution in vivo cine magnetic resonance
      imaging (cine-MRI) on a vertical 11.7-T MR system and to investigate the
      stability of normal and failing mouse hearts in the vertical position. MATERIALS
      AND METHODS: To optimize the method on a high-field system, various MR-related
      parameters, such as relaxation times and the need for respiratory gating, were
      quantitatively investigated. High-resolution cine-MRI was applied to normal mice
      and to a murine heart failure model. Cardiac functional parameters were compared
      to matched mice imaged previously on a horizontal MR system. RESULTS: A T(1) of
      1.10 +/- 0.27 seconds and a T(2) of 18.5 +/- 3.9 msec were measured for murine
      myocardial tissue. A quantitative analysis also proved respiratory gating to be
      essential for obtaining artifact-free cine images in the vertical position at
      this field strength. Cardiac functional parameters of mice, obtained within one
      hour, agreed well with those from previous studies of mice in the horizontal
      position. CONCLUSION: This work shows that MR systems with a vertical bore design
      can be used to accurately measure cardiac function in both normal and chronically
      failing mouse hearts within one hour. The increased signal-to-noise ratio (SNR)
      due to the higher field strength could be exploited to obtain higher temporal and
      spatial resolution compared to previous studies that were performed on horizontal
      systems with lower field strengths.

PMID- 14635155
TI  - Auto-SENSE perfusion imaging of the whole human heart.
AB  - PURPOSE: To show the application of auto-sensitivity encoding (SENSE)-a self
      calibrating parallel imaging technique-to first pass perfusion imaging of the
      whole human heart. MATERIALS AND METHODS: The self-calibrating parallel imaging
      method auto-SENSE was implemented for a saturation recovery turbo-fast low-angle
      shot (FLASH) sequence on a 1.5-T scanner using a standard four-element body
      phased array coil. By reducing the acquisition time per slice by a factor of two
      compared to conventional turbo FLASH imaging, the number of imaged slices could
      be doubled to six to ten with an unchanged temporal resolution of one image per
      heartbeat. This technique has been tested in eight healthy volunteers for
      contrast-enhanced heart perfusion imaging. RESULTS: Auto-SENSE heart perfusion
      imaging with improved coverage of the human heart could be performed successfully
      in all volunteers. A first quantitative comparison of perfusion values between
      the auto-SENSE and the non-SENSE techniques shows good agreement. CONCLUSION:
      Auto-SENSE allows perfusion imaging of the whole human heart without gaps.

PMID- 14635156
TI  - Magnetic resonance imaging of the liver with ultrashort TE (UTE) pulse sequences.
AB  - PURPOSE: To assess the feasibility of imaging the liver in volunteers and
      patients with ultrashort echo time (UTE) pulse sequences. MATERIALS AND METHODS:
      Seven normal controls as well as 12 patients with biopsy-proven generalized liver
      disease and three patients with focal disease were examined using pulse sequences
      with initial TEs of 0.08 msec followed by three later echoes, with or without
      frequency-based fat suppression. T(2)* values were calculated from regions of
      interest in the liver. RESULTS: Good image quality was obtained in each subject.
      There was a highly significant difference in the mean T(2)* values between the
      normal controls and patients with generalized liver disease (P = 0.001). T(2)*
      was significantly decreased in hemochromatosis (P = 0.002) and increased in
      cirrhosis (P = 0.04), compared with controls. T(2)* also correlated with
      functional status assessed by Child's grade (P = 0.001). A hepatocellular
      carcinoma showed reduced short T(2) components in the region of thermal ablation
      and evidence of a subcapsular hematoma which were not apparent with conventional
      imaging. CONCLUSIONS: Imaging of the liver with UTE sequences showed good image
      quality and tolerance of abdominal motion. T(2)* was specifically correlated with
      the presence of hemochromatosis, cirrhosis, and functional grade. Imaging of
      short T(2) relaxation components may provide useful information in disease.

PMID- 14635157
TI  - Measurement of single-kidney glomerular filtration rate using a contrast-enhanced
      dynamic gradient-echo sequence and the Rutland-Patlak plot technique.
AB  - PURPOSE: To determine the accuracy of single-kidney glomerular filtration rate
      (GFR) determination using contrast-enhanced dynamic magnetic resonance imaging
      (MRI) and the Rutland-Patlak plot technique. MATERIALS AND METHODS: Twenty-eight
      adult patients were included. As reference method, the GFR was measured by plasma
      clearance using a small bolus injection of iopromide. A three-dimensional
      gradient-echo (GRE) sequence with a flip angle of 50 degrees was used for MRI;
      this showed a good linear relationship between gadolinium (Gd)-DTPA concentration
      and signal change when measured up to a Gd-DTPA concentration of 10 mmol/liter. A
      slab containing both kidneys and the abdominal aorta was measured 30 times in
      approximately 3.5 minutes. During this measurement, 15 mL of Gd-DTPA, 0.5
      mol/liter diluted to a volume of 60 mL, was injected over 60 seconds. A Rutland
      Patlak plot was calculated from the signal changes in the aorta and the renal
      parenchyma. Single-kidney GFR was calculated for different time windows from the
      Rutland-Patlak plot slope. RESULTS: The best correlation compared to the
      reference method was found with the GFR calculated from the slope of the Rutland
      Patlak plot 40-110 seconds postaortic rise. Pearson's correlation coefficient was
      r = 0.86, SD was 14.8 mL/minute. In many of the patients, a decrease of the renal
      signal was observed in the excretory phase, which was probably caused by very
      high Gd-DTPA concentrations in the collecting tubules. CONCLUSION: Single-kidney
      GFR can be calculated from dynamic contrast-enhanced MRI. We found a promising
      correlation of global GFR calculated by MRI compared to the reference method. In
      any future study, the amount of Gd-DTPA should by reduced to avoid artificial
      signal drop in the excretory phase induced by the T2* effect.

PMID- 14635158
TI  - Uterine peristalsis shown on cine MR imaging using ultrafast sequence.
AB  - PURPOSE: To demonstrate and evaluate uterine peristalsis on cine magnetic
      resonance imaging (MRI) using ultrafast imaging. MATERIALS AND METHODS: Serial MR
      uterine images (300) were obtained from 15 normal volunteers over four menstrual
      phases using true fast imaging with steady-state precession (true FISP) technique
      over 117 seconds and videotaped. Three radiologists independently evaluated
      videotapes of 59 studies. Uterine peristalsis was defined as wavy movements of
      subendometrial myometrium or endometrium. Interobserver reliability was evaluated
      using a Kappa coefficient. Fifty-four studies obtained in appropriate phases were
      analyzed. RESULTS: Cine MRI displayed uterine peristalsis in 30 of 59 studies;
      consensus reading showed direction in 23 studies. Reliability between the final
      consensus of the recognition of uterine peristalsis and those of the three
      readers was extremely concordant, with a Kappa coefficient of 0.908. Wave
      direction was cervico-fundal in follicular and periovulatory phases, with
      frequency of contraction waves being 1.2-2.3 per minute in positive studies.
      CONCLUSION: Uterine peristalsis was demonstrated on cine MR using ultrafast MRI.
      Direction and frequency of peristaltic waves are closely related to menstrual
      cycle phases. Supplementary material for this article can be found on the JMRI
      website at http://www.interscience.wiley.com/jpages/1053-1807/suppmat/index.html.

PMID- 14635159
TI  - Real-time imaging of skeletal muscle velocity.
AB  - PURPOSE: To test the feasibility of using real-time phase contrast (PC) magnetic
      resonance imaging (MRI) to track velocities (1-20 cm/second) of skeletal muscle
      motion. MATERIALS AND METHODS: To do this we modified a fast real-time spiral PC
      pulse sequence to accommodate through-plane velocity encoding in the range of -20
      to +20 cm/second. We successfully imaged motion of the biceps brachii and triceps
      brachii muscles during elbow flexion and extension in seven unimpaired adult
      subjects using real-time PC MRI. RESULTS: The velocity data demonstrate that the
      biceps brachii and the triceps brachii, antagonistic muscles, move in opposite
      directions during elbow flexion and extension with velocity values in the muscle
      tissue ranging from -10 to +10 cm/second. CONCLUSION: With further development,
      real-time PC MRI may provide a means to analyze muscle function in individuals
      with neurologic or movement disorders who cannot actively complete the repeated
      motions required for dynamic MRI techniques, such as cine PC MRI, that are more
      commonly used in musculoskeletal biomechanics applications.

PMID- 14635160
TI  - Proton magnetic resonance spectroscopy as a potential tool for differentiating
      between abdominal fluid collections.
AB  - PURPOSE: To determine the utility of proton magnetic resonance spectroscopy (MRS)
      in distinguishing abdominal fluid types. MATERIALS AND METHODS: Abdominal fluid
      samples were obtained from patients undergoing therapeutic percutaneous drainage.
      In vitro spectroscopy was performed using a 1.5-T scanner and a head coil. Single
      voxel spectra were obtained using a point resolved spin-echo sequence with water
      suppression (TR/TE 2000 msec/35 msec). The peak pattern for each sample was
      examined and the signal-to-noise ratio (SNR) estimated (ratio of tallest peak to
      noise at <0 ppm). RESULTS: Thirty-five samples were analyzed: purulent collection
      (eight), serosanguinous collection (eight), non-chylous ascites (six), chylous
      ascites (one), bile (seven), and bile with iodinated contrast media (five). The
      mean SNR of the dominant peak was: purulent collection, 12.7; serosanguinous
      collection, 3.2; non-chylous ascites, 2.4; chylous ascites, 8.8; bile, 1.4; and
      bile with contrast media, 60.8. Pus samples had a broad based peak pattern with
      continuous signal of >1.5 ppm width situated within the range 0.2-2.5 ppm, not
      found in other samples. Chylous ascites (one sample) had a distinctive peak at
      1.2 ppm. Bile with contrast had three peaks at 3.5/3.6, 2.6, and 2.1 ppm. No
      other patterns were found to be discriminatory. Common non-specific patterns seen
      included a bifid peak at 1.1-1.3 ppm and a broad based peak situated between 3
      and 4 ppm. CONCLUSIONS: The H1 spectra of purulent fluid has a higher SNR than
      common non-purulent abdominal fluids and a distinct broad based peak pattern from
      0.2-2.5 ppm. Proton spectroscopy may be a useful tool for distinguishing purulent
      from non-purulent intra-abdominal collections.

PMID- 14635161
TI  - Application of the keyhole technique to T1rho relaxation mapping.
AB  - PURPOSE: To demonstrate the feasibility of using the keyhole technique to
      minimize error in a least squares regression estimation of T(1rho) from magnetic
      resonance (MR) image data. MATERIALS AND METHODS: The keyhole method of partial k
      space acquisition was simulated using data from a virtual phantom and MR images
      of ex vivo bovine and in vivo human cartilage. T(1rho) maps were reconstructed
      from partial k-space (keyhole) image data using linear regression, and error was
      measured with relation to T(1rho) maps created from the full k-space images. An
      error model was created based on statistical theory and fitted to the error
      measurements. RESULTS: T(1rho) maps created from keyhole images of a human knee
      produced levels of error on the order of 1% while reducing standard image
      acquisition time approximately by half. The resultant errors were strongly
      correlated with expectations derived from statistical theory. CONCLUSION: The
      error model can be used to analytically optimize the keyhole method in order to
      minimize the overall error in the estimation of the relaxation parameter of
      interest. The keyhole method can be generalized to significantly expedite all
      forms of relaxation mapping.

PMID- 14635163
TI  - Genetic Analysis Workshop 13: introduction to workshop summaries.

PMID- 14635164
TI  - Genetic analysis of phenotypes derived from longitudinal data: Presentation Group
      1 of Genetic Analysis Workshop 13.
AB  - The participants of Presentation Group 1 used the GAW13 data to derive new
      phenotypes, which were then analyzed for linkage and, in one case, for
      association to the genetic markers. Since the trait measurements ranged over
      longer time periods, the participants looked at the time dependence of particular
      traits in addition to the trait itself. The phenotypes analyzed with the
      Framingham data can be roughly divided into 1) body weight-related traits, which
      also include a type 2 diabetes progression trait, and 2) traits related to
      systolic blood pressure. Both trait classes are associated with metabolic
      syndrome. For traits related to body weight, linkage was consistently identified
      by at least two participating groups to genetic regions on chromosomes 4, 8, 11,
      and 18. For systolic blood pressure, or its derivatives, at least two groups
      obtained linkage for regions on chromosomes 4, 6, 8, 11, 14, 16, and 19. Five of
      the 13 participating groups focused on the simulated data. Due to the rather
      sparse grid of microsatellite markers, an association analysis for several traits
      was not successful. Linkage analysis of hypertension and body mass index using
      LODs and heterogeneity LODs (HLODs) had low power. For the glucose phenotype, a
      combination of random coefficient regression models and variance component
      linkage analysis turned out to be strikingly powerful in the identification of a
      trait locus simulated on chromosome 5. Haseman-Elston regression methods, applied
      to the same phenotype, had low power, but the above-mentioned chromosome 5 locus
      was not included in this analysis.

PMID- 14635165
TI  - Longitudinal data analysis in pedigree studies.
AB  - Longitudinal family studies provide a valuable resource for investigating genetic
      and environmental factors that influence long-term averages and changes over time
      in a complex trait. This paper summarizes 13 contributions to Genetic Analysis
      Workshop 13, which include a wide range of methods for genetic analysis of
      longitudinal data in families. The methods can be grouped into two basic
      approaches: 1) two-step modeling, in which repeated observations are first
      reduced to one summary statistic per subject (e.g., a mean or slope), after which
      this statistic is used in a standard genetic analysis, or 2) joint modeling, in
      which genetic and longitudinal model parameters are estimated simultaneously in a
      single analysis. In applications to Framingham Heart Study data, contributors
      collectively reported evidence for genes that affected trait mean on chromosomes
      1, 2, 3, 5, 8, 9, 10, 13, and 17, but most did not find genes affecting slope.
      Applications to simulated data suggested that even for a gene that only affected
      slope, use of a mean-type statistic could provide greater power than a slope-type
      statistic for detecting that gene. We report on the results of a small experiment
      that sheds some light on this apparently paradoxical finding, and indicate how
      one might form a more powerful test for finding a slope-affecting gene. Several
      areas for future research are discussed.

PMID- 14635166
TI  - Consistency of genetic analyses in longitudinal data: observations from the GAW13
      Framingham Heart Study data.
AB  - This paper examines the consistency of genetic analyses across time, both in the
      context of replicating results from one data collection point to the next, and
      from the perspective of modeling longitudinal processes. This summary originates
      from the examination of findings from nine papers from Genetic Analysis Workshop
      (GAW) 13 that reported on analyses of longitudinal data of a variety of traits
      from the Framingham Heart Study. These analyses include both assessments of
      consistency of aggregate genetic effects, in the form of estimation of
      heritability and relative risk of disease, as well as localization of
      quantitative trait loci (QTLs) by genome-wide linkage screens. Consistency varied
      widely by trait, possibly reflecting differences in measurement error, secular
      trends, or underlying biological features such as genotype x age interaction.
      Quantitatively, comparing magnitudes of estimates across age or time,
      heritability estimates showed greater consistency than LOD scores. However,
      qualitatively, the same regions of interest were often identified in genome scans
      from different time points or different ages. Estimates of sibling recurrence
      risk, on the other hand, showed little consistency. Heritabilities were greater
      when participants were matched by age than when they were matched by date of
      examination. Multivariate approaches, either in use of multiple traits or in use
      of multiple measures of the same trait, appeared to provide stronger genetic
      signals both for relative risk and for linkage. Finally, modeling of longitudinal
      processes provided evidence for genotype x age interactions that may partially
      explain variation in results of genetic analyses across time or age.

PMID- 14635167
TI  - Summary report: Missing data and pedigree and genotyping errors.
AB  - Genetic epidemiology is faced with mapping complex traits to genes with
      relatively small effects whose phenotypes may be modulated by temporal factors.
      To do this, detailed and accurate data must be available on families, perhaps
      collected over time. The Framingham Heart Study data supplied to Genetic Analysis
      Workshop 13 (GAW13), along with its simulated counterpart, contain longitudinal
      measurements and genomic scan data on 2,885 individuals in 330 families, and
      offer an opportunity to examine data quality and completeness issues as they
      affect analytical conclusions. Six GAW13 contributions applied methods to deal
      with missing data, both phenotypic and genotypic, at a single time point and
      longitudinally, and with possible errors in pedigree structure and genotypes. The
      methods included missing phenotypic data imputation by Markov chain Monte Carlo
      sampling, propensity scoring, regression, and adjusted mean values, as well as
      the assessment of transmission-disequilibrium tests when missing marker data may
      be allele-specific. Pedigree structural errors were found by genome-wide allele
      sharing probabilities, while Mendelian consistent genotype errors were evaluated
      through likelihoods of double-recombination events. Each of the methods reviewed
      here offered insights into how to better take advantage of large, time-dependent,
      familial data sets. However, no one of them dealt with the longitudinal and
      familial aspects simultaneously. Overall, more consideration needs to be given to
      the effects that missing data and data errors have on our ability to map complex
      traits efficiently and accurately.

PMID- 14635168
TI  - Effects of covariates: a summary of Group 5 contributions.
AB  - This report summarizes the contributions of Genetic Analysis Workshop 13 (GAW13)
      related to the use of covariates in genetic analysis. Seven papers are
      summarized, five of which analyzed the Framingham Heart Study Data, and two the
      simulated data. Five papers examined the role of covariates in linkage analysis,
      using a variety of statistical approaches including affected sibling pair
      analysis, conditional logistic regression, and variance components methods. One
      paper examined the impact of covariates on family-based association analysis. In
      each of these papers, the detection of genetic effects could be influenced by the
      incorporation of covariates. The final paper examined the role of transmission
      ratio distortion in the analysis of complex traits and the role of covariates in
      the variability in transmission ratio distortion. While each paper takes a
      different approach to the genetic analysis of complex traits, a common thread
      running through each is that the inclusion of covariates can have a substantial
      impact on the results of the analysis. Care must be taken to understand how the
      covariates are being used in each analysis, what assumptions are being made, and
      how these assumptions might affect the results and their interpretation. Finally,
      the results of Group 5 studies show that inclusion of covariates can increase the
      power to detect genes for complex traits, and has the potential to advance an
      understanding of the role of genes in these complex traits.

PMID- 14635169
TI  - Group 6: Pleiotropy and multivariate analysis.
AB  - Analysis techniques using data on several traits simultaneously allow researchers
      to dissect the genetic architecture affecting correlated traits, and can increase
      the power to detect pleiotropic genes, i.e., genes that influence two or more
      traits. Several of the papers in this group from Genetic Analysis Workshop 13
      presented promising univariate summaries of multiple traits that detected linkage
      signals that standard single-trait univariate methods did not. Other papers found
      linkage signals using multivariate techniques that univariate techniques missed,
      although this was not uniformly the case. Some papers also considered the
      correlation among measurements of a single trait taken at different ages to
      assess whether the genetic architecture of the trait changed over age.
      Applications of the Framingham Heart Study data identified major loci jointly
      influencing body mass index and high-density lipoprotein cholesterol, high
      density lipoprotein cholesterol and triglycerides, total cholesterol and
      triglycerides, and various combinations of four traits involved in metabolic
      syndrome.

PMID- 14635170
TI  - Data mining and computationally intensive methods: summary of Group 7
      contributions to Genetic Analysis Workshop 13.
AB  - The Framingham Heart Study data, as well as a related simulated data set, were
      generously provided to the participants of the Genetic Analysis Workshop 13 in
      order that newly developed and emerging statistical methodologies could be tested
      on that well-characterized data set. The impetus driving the development of novel
      methods is to elucidate the contributions of genes, environment, and interactions
      between and among them, as well as to allow comparison between and validation of
      methods. The seven papers that comprise this group used data-mining methodologies
      (tree-based methods, neural networks, discriminant analysis, and Bayesian
      variable selection) in an attempt to identify the underlying genetics of
      cardiovascular disease and related traits in the presence of environmental and
      genetic covariates. Data-mining strategies are gaining popularity because they
      are extremely flexible and may have greater efficiency and potential in
      identifying the factors involved in complex disorders. While the methods grouped
      together here constitute a diverse collection, some papers asked similar
      questions with very different methods, while others used the same underlying
      methodology to ask very different questions. This paper briefly describes the
      data-mining methodologies applied to the Genetic Analysis Workshop 13 data sets
      and the results of those investigations.

PMID- 14635171
TI  - Summary of Group 8: Development and extension of linkage methods.
AB  - The diverse contributions to Group 8 focus on the development and extension of
      linkage methods, and share themes that are organized around approaches to
      analysis. The themes discussed include issues of the accuracy of estimates of
      marker identity-by-descent (IBD) information, the influence of such IBD
      information on linkage detection, and methods for dealing with genetic
      heterogeneity and multiple testing. In addition, challenges were identified and
      solutions were offered for coping with some of the common problems of complex
      trait analysis, including trait model selection and computational compromises.
      Analytic approaches based on Bayesian and Monte Carlo methods were prominent, and
      provided optimistic results.

PMID- 14635172
TI  - Modeling and dissection of longitudinal blood pressure and hypertension
      phenotypes in genetic epidemiological studies.
AB  - We discuss analyses of the Genetic Analysis Workshop 13 data from the Framingham
      Heart Study and simulations based on this study. We summarize analyses that
      investigated measures of systolic blood pressure or hypertension as the main
      phenotype, with the main focus being the modeling of this complex longitudinal
      phenotype. The approaches include familial aggregation methods and one-stage and
      two-stage linkage methods. For one-stage linkage methods, phenotype modeling is
      carried out jointly with the linkage analysis or incorporated in the analysis
      design. For two-stage linkage methods, phenotypes are first modeled in order to
      develop summary measures that are then analyzed in a subsequent linkage analysis.
      Results depend on phenotype selection and on how analyses account for
      longitudinality, treatment effects, and heterodasticity.

PMID- 14635173
TI  - Analysis of metabolic syndrome phenotypes in Framingham Heart Study families from
      Genetic Analysis Workshop 13.
AB  - Twelve teams of investigators constituted a group which analyzed phenotypes
      related to metabolic syndrome, making use of the available longitudinal
      measurements from the family component of the Framingham Heart Study or the
      simulated data, as distributed by Genetic Analysis Workshop 13 (GAW13). Body mass
      index, obesity, lipid abnormalities, glucose, or combinations of these traits
      were analyzed by this group. A wide variety of approaches were taken to construct
      phenotypes from the longitudinal measurements, including considering single or
      multiple cross-sectional time points, single ages, minimum values, maximum
      values, means, other lifetime values, ever/never dichotomy, or age at onset of
      some threshold value. Approaches also differed in the family structures utilized
      (sib pairs to full extended pedigrees), the genetic data considered (two-point or
      multipoint), and the statistics calculated (model-free and parametric), and led
      to a diverse set of analyses being performed. Inferences were made about
      heritability, and attempts were made to map underlying genes. Over 40 genome-wide
      linkage analyses were conducted. Despite the broad range of approaches, several
      regions of the genome were repeatedly identified across multiple analyses.

PMID- 14635174
TI  - Genetic analysis workshop 13: Summary of analyses of alcohol and cigarette use
      phenotypes in the Framingham Heart Study.
AB  - Data from the Framingham Heart Study were provided for Genetic Analysis Workshop
      13. This paper summarizes six contributed papers that focused on the analysis of
      the longitudinal alcohol and/or cigarette use phenotypes available in these data,
      with the goal of detecting genes influencing these traits. For several of these
      contributions, the primary phenotype was maximum daily substance use reported
      over the longitudinal data. Others focused on a cross section by taking the daily
      use reported at a fixed time interval for all individuals, and others considered
      dichotomous phenotypes defined by thresholds of use. A variety of covariates were
      considered, including age (or year of birth) and sex. Most studies included
      unexposed individuals (those reporting no alcohol/cigarette use at all available
      assessments) in the linkage analyses, though one study compared results when
      defining the phenotype for unexposed individuals to be zero vs. defining the
      phenotype for unexposed individuals to be unknown. Linkage findings varied across
      studies. However, there was some concordance of evidence on chromosome 9 for
      alcohol traits, and of weaker evidence on chromosome 20 for cigarette traits.
      Analytical issues arose which may be crucial for genetic studies of substance use
      and dependence, including the choice of how to handle unexposed or substance
      naive individuals, use of dichotomous vs. quantitative traits, and consideration
      of transformations and covariates.

PMID- 14635175
TI  - Introduction: biorational insecticides-mechanism and application.

PMID- 14635176
TI  - Chloride channels as tools for developing selective insecticides.
AB  - Ligand-gated chloride channels underlie inhibition in excitable membranes and are
      proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1))
      receptor/chloride ionophore complex is the primary site of action for a number of
      currently used insecticides, such as lindane, endosulfan, and fipronil. These
      compounds act as antagonists by stabilizing nonconducting conformations of the
      chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal
      inhibition, which leads to hyperexcitation of the central nervous system,
      convulsions, and death. We recently investigated the mode of action of the
      silphinenes, plant-derived natural compounds that structurally resemble
      picrotoxinin. These materials antagonize the action of GABA on insect neurons and
      block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a
      noncompetitive manner. In mammals, avermectins have a blocking action on the GABA
      gated chloride channel consistent with a coarse tremor, whereas at longer times
      and higher concentrations, activation of the channel suppresses neuronal
      activity. Invertebrates display ataxia, paralysis, and death as the predominant
      signs of poisoning, with a glutamate-gated chloride channel playing a major role.
      Additional target sites for the avermectins or other chloride channel-directed
      compounds might include receptors gated by histamine, serotonin, or
      acetylcholine.The voltage-sensitive chloride channels form another large gene
      family of chloride channels. Voltage-dependent chloride channels are involved in
      a number of physiological processes including: maintenance of electrical
      excitability, chloride ion secretion and resorption, intravesicular
      acidification, and cell volume regulation. A subset of these channels is affected
      by convulsants and insecticides in mammals, although the role they play in acute
      lethality in insects is unclear. Given the wide range of functions that they
      mediate, these channels are also potential targets for insecticide development.

PMID- 14635177
TI  - Novaluron (Rimon), a novel IGR: potency and cross-resistance.
AB  - The potency of novaluron on laboratory susceptible and field strains of S.
      littoralis resembles that of chlorfluazuron and both compounds are about 20-fold
      more potent than teflubenzuron. No appreciable resistance to novaluron or
      chlorfluazuron was observed in a field strain of Spodoptera littoralis collected
      from cucumber field in the central part of Israel. On the other hand, the field
      strain showed a mild resistance of about 4-fold to teflubenzuron as compared to
      the laboratory susceptible strain. A very resistant colony of Bemisia tabaci to
      pyriproxyfen (1,200- to 2,000-fold) showed no appreciable cross-resistance to
      novaluron. Two field colonies of B. tabaci pressurized with acetamiprid or
      thiamethoxam for 22 generations, resulting in a 30- to 50-fold resistance to
      acetamiprid and thiamethoxam, has no cross-resistance to novaluron. The above
      results are of special interest, indicating a possible alternation between
      novaluron, pyriproxyfen, and neonicotinoids in insecticide-resistance management
      programs aiming at preventing resistance development to these novel groups of
      insecticides against important pests such as whitefly and lepidopteran species.

PMID- 14635178
TI  - Identification of biochemical markers linked to neonicotinoid cross resistance in
      Bemisia tabaci (Hemiptera: Aleyrodidae).
AB  - The whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae), is a serious pest in many
      cropping systems world-wide and occurs in different biotypes. The most widespread
      one is the B-type, whereas the Q-biotype is nowadays still mostly restricted to
      Southern Spain. Neonicotinoid cross-resistance is known at a high level in Q
      types from Spain and individual samples collected in Italy and Germany. Now we
      detected for the first time high neonicotinoid cross-resistance in a B-type from
      Israel. Target site resistance to imidacloprid using [(3)H]imidacloprid in
      nicotinic acetylcholine receptor (nAChR) binding assays could not be detected in
      any of these highly resistant strains. The impact of metabolizing enzymes such as
      esterases, glutathione S-transferases, and cytochrome P450-dependent
      monooxygenases in neonicotinoid resistance was studied biochemically with
      artificial substrates. Monooxygenase activity was increased 2-3-fold in
      moderately resistant strains (RF approximately 30) and even 5-6-fold in highly
      resistant strains (RF approximately 1,000). Only monooxygenase activity
      correlated with imidacloprid, thiamethoxam and acetamiprid resistance and,
      therefore, monooxygenases seem to be the only enzyme system responsible for
      neonicotinoid resistance in B. tabaci Q- and B-types. The oxidative degradation
      of imidacloprid in resistant Q-type strains could be confirmed by metabolism
      studies of [(14)C]imidacloprid in vivo. Five-hydroxy-imidacloprid could be
      detected as the only main metabolite. The insecticidal activity and binding
      affinity to nAChR of this compound was 10 times lower than imidacloprid itself in
      B. tabaci.

PMID- 14635179
TI  - Inheritance of pyriproxyfen resistance in the whitefly, Bemisia tabaci (Q
      biotype).
AB  - The inheritance of resistance to pyriproxyfen, an insect growth regulator (a
      juvenoid, with ovicidal and larvicidal activities), was studied in the whitefly
      Bemisia tabaci (Gennadius). Two parental strains, both belonging to Q biotype,
      were assayed with pyriproxyfen; a susceptible strain (ALM-1) originating from
      Spain and a pyriproxyfen-resistant one (Pyri-R) from Israel. The resistance ratio
      between the two parental strains was approximately 7,000-fold. Concentration
      mortality lines for F(1) heterozygous females from reciprocal crosses (SS female
      symbol X R male symbol and RR female symbol X S male symbol ) were derived by
      statistical modelling and proved intermediate to those of the parents. The pooled
      degree of dominance from both reciprocal crosses was +0.26, indicating that
      resistance was incompletely or partially dominant. Mortality curves for F(2)
      males produced by virgin F(1) heterozygous females displayed a broad plateau at
      50% mortality, indicating that resistance to pyriproxyfen in B. tabaci is
      conferred primarily by a mutant allele at a single locus. The role of arrhenotoky
      in influencing the mode of inheritance of resistance, and its selection in field
      populations, is discussed.

PMID- 14635180
TI  - Ecdysone agonists: mechanism and importance in controlling insect pests of
      agriculture and forestry.
AB  - Molting is the result of the expression of a cascade of genes that is
      sequentially both up and down-regulated by the molting hormone, 20
      hydroxyecdysone (20E), which is secreted as a pulse during each instar. Benzoyl
      hydrazine analogs of 20E act like the native molting hormone at the molecular
      level by binding with the ecdysone receptor complex and transactivating a
      succession of molt initiating transcription factors that, in turn, induce the
      expression of a group of molt-related genes. As a result of the expression of
      these up-regulated genes, the larva undergoes apolysis and head capsule slippage
      and takes on the appearance of the pharate larva. However, unlike 20E, which is
      cleared at this juncture, allowing the down-regulated genes to be expressed,
      these synthetic analogs bind strongly to the receptors and remain in place and
      repress all the down-regulatory genes such as the ones necessary for cuticle
      elaboration, sclerotization, and ecdysis resulting in a developmental arrest in
      this state. As a result, the treated larva goes into a precocious incomplete molt
      that is lethal. Two of the analogs, tebufenozide and methoxyfenozide, are
      lepidopteran specific and have good control potential for open feeding larvae
      that ingest this material while a third one, halofenozide, acts on coleopteran
      larvae. Since they specifically act through an insect receptor complex, they have
      little or no effect on non-target species, making them environmentally attractive
      pest control agents. Some insects, however, show resistance to these analogs and
      this could be, inter alia, due to an ATP Binding Cassette Transporter like system
      that selectively pumps out the analogs.

PMID- 14635181
TI  - Bt: mode of action and use.
AB  - The insecticidal toxins from Bacillus thuringiensis (Bt) represent a class of
      biopesticides that are attractive alternatives to broad-spectrum "hard"
      chemistries. The U.S. Food Quality Protection Act and the European Economic
      Council directives aimed at reducing the use of carbamate and organophosphate
      insecticides were expected to increase the use of narrowly targeted, "soft"
      compounds like Bt. Here we summarize the unique mode of action of Bt, which
      contributes to pest selectivity. We also review the patterns of Bt use in general
      agriculture and in specific niche markets. Despite continued predictions of
      dramatic growth for biopesticides due to US Food Quality Protection Act-induced
      cancellations of older insecticides, Bt use has remained relatively constant,
      even in niche markets where Bt has traditionally been relatively high.

PMID- 14635182
TI  - Botanical insecticides for controlling agricultural pests: piperamides and the
      Colorado Potato Beetle Leptinotarsa decemlineata say (Coleoptera: Chrysomelidae).
AB  - The efficacy of extracts from two Piperaceae species, Piper nigrum L. and P.
      tuberculatum Jacq. were evaluated using larvae and adults of the Colorado Potato
      Beetle Leptinotarsa decemlineata (Say). Young larvae and neonates were the most
      susceptible; a 24-h LD(50) of 0.064% extract of P. tuberculatum was determined
      for 4-day-old larvae, while 0.05% extract of P. nigrum reduced larval survival up
      to 70% within one week after treatment of potato Solanum tuberosum L.
      (Solanaceae) plants. When an insecticide resistant strain of L. decemlineata
      larvae was tested with the P. tuberculatum extract, there was less than a 2-fold
      tolerance ratio compared to the 22-fold tolerance ratio to cypermethrin, a
      pyrethroid. Older larvae, pre-pupal stage and adults, were less sensitive to the
      P. nigrum extracts; the 24-h LD(50) was 0.5% (95% C.I. = 0.36, 0.65). However,
      the same concentration was equally effective under field conditions. In the
      greenhouse, P. nigrum at 0.5% was as effective at reducing adult L. decemlineata
      feeding as combinations with 2 separate botanical mixtures, garlic and lemon
      grass oil. Under field conditions, the residual activity of the P. nigrum
      extracts was less than 3 h. When adult L. decemlineata were placed on treated
      plants exposed to full sunlight for 0, 1.5, and 3 h, leaf damage progressively
      increased as the main active compound, piperine, was found to degrade by 80%
      after 3 h. An in vitro polysubstrate monoxygenase (PSMO) enzyme assay, using the
      substrate methoxyresorufin O-demethylation (MROD), determined that the principal
      P. nigrum active compound, piperine, is responsible for inhibition of that
      specific enzyme. The results suggest that Piper extracts could be used
      effectively as contact botanical insect control agents to protect potato plants
      from developing L. decemlineata larvae at concentrations less than 0.1%. There is
      also potential for Piper extracts to control insecticide resistant populations in
      conjunction with other integrated pest management (IPM) strategies used in
      conventional and organic agriculture.

PMID- 14635183
TI  - In vivo imaging and tumor therapy with the sodium iodide symporter.
AB  - There has been great progress in the design of vectors for cancer gene therapy.
      However, it has been difficult to translate success in the laboratory into
      clinical practice. A major hurdle in understanding these failures has been the
      relative difficulty in monitoring repeatedly and non-invasively the
      biodistribution, gene expression and replication of these viral vector systems.
      With the advent of molecular imaging technology, this deficiency is being rapidly
      rectified. A number of reporter genes have been used to monitor gene expression.
      In this review, we discuss the role of the sodium iodide symporter (NIS) as a
      reporter and therapeutic gene for cancer gene therapy when combined with various
      radioactive isotopes.

PMID- 14635184
TI  - Molecular imaging of proteolytic activity in cancer.
AB  - The early detection of both primary tumors and metastatic disease continue to be
      significant challenges in the diagnosis and staging of cancer. The growing
      recognition of the role of proteinases and proteolytic cascades in both the
      growth and metastasis of tumors has led to the development not only of
      therapeutic strategies using proteinase inhibitors, but also of methods to detect
      and image tumors in vivo via tumor-associated proteolytic activities. These
      imaging strategies derive from the enhanced sensitivity afforded by amplification
      that can be obtained by enzymatic processing to increase the efficacy of imaging
      "contrast agents" coupled with the inherent substrate specificity and selectivity
      of proteinases. This review describes key proteinases important in cancer
      progression, the strategies that have been devised to detect and image
      proteolytic activity in vivo, and the potential for this kind of functional
      imaging to serve as a marker for targeted therapy. The intent is to draw
      attention to the developing methods of molecular imaging to facilitate not only
      cancer diagnosis, but also for devising strategies for individualized targeted
      therapy and non-invasive monitoring of therapeutic efficacy.

PMID- 14635185
TI  - Human heme oxygenase: cell cycle-dependent expression and DNA microarray
      identification of multiple gene responses after transduction of endothelial
      cells.
AB  - The purpose of the present study was to examine the role of human heme oxygenase
      (human HO-1) in cell cycle progression following exposure to heme or human HO-1
      gene transfer and to identify target genes associated with human HO-1-meditated
      increases in cell cycle progression using cDNA microarray technology. Heme
      induced robust human HO-1 expression in quiescent human microvessel endothelial
      cells cultured in 1% FBS and the levels of human HO-1 expression progressively
      declined without a change in the cell cyclin. To identify genes regulated by
      human HO-1 in the cell cycle, human endothelial cells were transduced with a
      retroviral vector encoded with human HO-1 gene or an empty vector. Transgene
      expression and functionality of the recombinant protein were assessed by Western
      blotting, enzyme activity, carbon monoxide, cGMP production, and cell cycle
      analysis. Human cDNA gene array and quantitative real-time RT-PCR were used to
      identify both known and novel differentially expressed genes in cells
      overexpressing human HO-1. Major findings were upregulation of several genes
      associated with cell cycle progression, including cyclin E and D; downregulation
      of cyclin-dependent kinase inhibitors p21 and p27, cyclin-dependent kinases 2, 5,
      and 6, and monocyte chemoattractant protein-1; and upregulation of growth
      factors, including vascular endothelial growth factor (VEGF) and vascular
      endothelial growth factor receptor I (VEGFRI), endothelial growth factor (EGF)
      and hepatic-derived growth factor (HDGF). These findings identify an array of
      gene responses to overexpression of human HO-1 and elucidate new aspects of human
      HO-1 signaling involved in cell growth.

PMID- 14635186
TI  - BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and
      osteogenesis.
AB  - The molecular mechanisms by which bone morphogenetic proteins (BMPs) promote
      skeletal cell differentiation were investigated in the murine mesenchymal stem
      cell line C3H10T1/2. Both BMP-7 and BMP-2 induced C3H10T1/2 cells to undergo a
      sequential pattern of chondrogenic followed by osteogenic differentiation that
      was dependent on both the concentration and the continuous presence of BMP in the
      growth media. Differentiation was determined by the expression of chondrogenesis
      and osteogenesis associated matrix genes. Subsequent experiments using BMP-7
      demonstrated that withdrawal of BMP from the growth media led to a complete loss
      of skeletal cell differentiation accompanied by adipogenic differentiation of
      these cells. Continuous treatment with BMP-7 increased the expression of Sox9,
      Msx 2, and c-fos during the periods of chondrogenic differentiation after which
      point their expression decreased. In contrast, Dlx 5 expression was induced by
      BMP-7 treatment and remained elevated throughout the time-course of skeletal cell
      differentiation. Runx2/Cbfa1 was not detected by ribonuclease protection assay
      (RPA) and did not appear to be induced by BMP-7. The sequential nature of
      differentiation of chondrocytic and osteoblastic cells and the necessity for
      continuous BMP treatment to maintain skeletal cell differentiation suggests that
      the maintenance of selective differentiation of the two skeletal cell lineages
      might be dependent on BMP-7-regulated expression of other morphogenetic factors.
      An examination of the expression of Wnt, transforming growth factor-beta (TGF
      beta), and the hedgehog family of morphogens showed that Wnt 5b, Wnt 11, BMP-4,
      growth and differentiation factor-1 (GDF-1), Sonic hedgehog (Shh), and Indian
      hedgehog (Ihh) were endogenously expressed by C3H10T1/2 cells. Wnt 11, BMP-4, and
      GDF-1 expression were inhibited by BMP-7 treatment in a dose-dependent manner
      while Wnt 5b and Shh were selectively induced by BMP-7 during the period of
      chondrogenic differentiation. Ihh expression also showed induction by BMP-7
      treatment, however, the period of maximal expression was during the later time
      points, corresponding to osteogenic differentiation. An interesting phenomenon
      was that BMP-7 activity could be further enhanced twofold by growing the cells in
      a more nutrient-rich media. In summary, the murine mesenchymal stem cell line
      C3H10T1/2 was induced to follow an endochondral sequence of chondrogenic and
      osteogenic differentiation dependent on both dose and continual presence of BMP-7
      and enhanced by a nutrient-rich media. Our preliminary results suggest that the
      induction of osteogenesis is dependent on the secondary regulation of factors
      that control osteogenesis through an autocrine mechanism.

PMID- 14635187
TI  - Induction of GADD gene expression by phenethylisothiocyanate in human colon
      adenocarcinoma cells.
AB  - Phenethylisothiocyanate (PEITC), a potential cancer chemopreventive agent,
      induces colon cancer cell death, but the mechanism is not entirely clear.
      Therefore, the aim of this study was to further clarify the molecular effects of
      PEITC in causing death of human colon adenocarcinoma cells. When incubated with
      PEITC, HCT-116 colonocytes showed morphological features characteristic of
      apoptosis, such as irregular cell shape, translocation of plasma membrane
      phosphatidylserine, and also chromatin condensation and fragmentation. These
      changes occurred after single-strand breaks in DNA were detected, suggesting that
      PEITC induced irreparable DNA damage, which in turn triggered the process of
      apoptosis. DNA macroarray analysis of a selected small cluster of apoptosis
      related genes revealed noticeably higher expression of only GADD45, which was
      confirmed by gene-specific relative RT-PCR analysis. This led to investigation of
      other GADD gene members possibly affected by PEITC. Whereas GADD34 mRNA
      expression increased just slightly, there was an appreciable elevation of the
      mRNA for GADD153, which is recognized as a pro-apoptotic gene. The effect of
      PEITC on GADD153 was attenuated by either actinomycin D or N-acetylcysteine,
      suggesting that PEITC-induced upregulation of GADD153 mRNA expression was partly
      at the level of transcriptional activation involving reactive oxygen species.
      Additionally, PEITC-induced upregulation of GADD153 mRNA expression did not
      appear to require p53, based on the observation that PEITC also increased GADD153
      mRNA expression in HCT-15 colonocytes, which are known to express mutant p53.
      These findings suggest that PEITC creates an oxidative cellular environment that
      induces DNA damage and GADD153 gene activation, which in turn helps trigger
      apoptosis.

PMID- 14635188
TI  - Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear
      matrix.
AB  - It has become obvious that a better understanding and potential elucidation of
      the nucleolar phosphoprotein B23 involving in functional interrelationship
      between nuclear organization and gene expression. In present study, protein B23
      expression were investigated in the regenerative hepatocytes at different periods
      (at days 0, 1, 2, 3, 4, 7) during liver regeneration after partial hepatectomy on
      the rats with immunohistochemistry and Western blot analysis. Another experiment
      was done with immunolabeling methods and two-dimensional (2-D) gel
      electrophoresis for identification of B23 in the regenerating hepatocytes and
      HepG2 cells (hepatoblastoma cell line) after sequential extraction with
      detergents, nuclease, and salt. The results showed that its expression in the
      hepatocytes had a locative move and quantitative change during the process of
      liver regeneration post-operation. Its immunochemical localization in the
      hepatocytes during the process showed that it moved from nucleoli of the
      hepatocytes in the stationary stage to nucleoplasm, cytoplasm, mitotic spindles,
      and mitotic chromosomes of the hepatocytes in the regenerating livers. It was
      quantitatively increased progressively to peak level at day 3 post-operation and
      declined gradually to normal level at day 7. It was detected in nuclear matrix
      protein (NMP) composition extracted from the regenerating hepatocytes and HepG2
      cells and identified with isoelectric point (pI) value of 5.1 and molecular
      weight of 40 kDa. These results indicated that B23 was a proliferate shuttle
      protein involving in cell cycle and cell proliferation associated with nuclear
      matrix.

PMID- 14635189
TI  - Transcriptional characterization of bone morphogenetic proteins (BMPs)-mediated
      osteogenic signaling.
AB  - Bone formation is presumably a complex and well-orchestrated process of
      osteoblast lineage-specific differentiation. As members of the TGFbeta
      superfamily, bone morphogenetic proteins (BMPs) play an important role in
      regulating osteoblast differentiation and subsequent bone formation. Several BMPs
      are able to induce de novo bone formation. Although significant progress has
      recently been made about the transcriptional control of osteoblast
      differentiation, detailed molecular events underlying the osteogenic process
      remain to be elucidated. In order to identify potentially important signaling
      mediators activated by osteogenic BMPs but not by non-osteogenic BMPs, we sought
      to determine the transcriptional differences between three osteogenic BMPs (i.e.,
      BMP-2, BMP-6, and BMP-9) and two inhibitory/non-osteogenic BMPs (i.e., BMP-3 and
      BMP-12). Through the microarray analysis of approximately 12,000 genes in pre
      osteoblast progenitor cells, we found that expression level of 203 genes (105 up
      regulated and 98 down-regulated) was altered >2-fold upon osteogenic BMP
      stimulation. Gene ontology analysis revealed that osteogenic BMPs, but not
      inhibitory/non-osteogenic BMPs, activate genes involved in the proliferation of
      pre-osteoblast progenitor cells towards osteoblastic differentiation, and
      simultaneously inhibit myoblast-specific gene expression. BMP-regulated
      expression of the selected target genes was confirmed by RT-PCR, as well as by
      the CodeLink Bioarray analysis. Our findings are consistent with the notion that
      osteogenesis and myogenesis are two divergent processes. Further functional
      characterization of these downstream target genes should provide important
      insights into the molecular mechanisms behind BMP-mediated bone formation.

PMID- 14635190
TI  - Biochemical and functional changes of rat liver spheroids during spheroid
      formation and maintenance in culture: I. morphological maturation and kinetic
      changes of energy metabolism, albumin synthesis, and activities of some enzymes.
AB  - In the process of isolated single liver cells coming together to form three
      dimensional spheroids, cells undergo dramatic environmental changes. How liver
      cells respond to these changes has not been well studied before. This study
      characterized the functional and biochemical changes during liver spheroid
      formation and maintenance. Spheroids were prepared in 6-well plates from freshly
      isolated liver cells from male Sprague rats by a gyrotatory-mediated method.
      Morphological formation, and functional and biochemical parameters of liver
      spheroids were evaluated over a period of 21 days in culture. Liver spheroid
      formation was divided into two stages, immature (1-5 days) and mature (>5 days),
      according to their size and shape, and changes in their functionality. Galactose
      and pyruvate consumption was maintained at a relatively stable level throughout
      the period of observation. However, glucose secretion and cellular GPT and GOT
      activities were higher in immature spheroids, decreased upto day 5 and remained
      stable thereafter. Cellular gamma-glutamyltransferase (gamma-GT) and lactate
      dehydrogenase (LDH) activities were initially undetectable or low and increased
      as spheroids matured. Albumin secretion decreased rapidly within the first 2 days
      and increased as spheroids matured. It is concluded that cells undergo functional
      and biochemical changes during spheroid formation following isolation of liver
      cells from intact tissue. Functionality and biochemical properties recovered and
      were maintained in mature spheroids. A relatively stable period (6-15 days) of
      functionality in mature spheroids was identified and is recommended for
      applications of the model.

PMID- 14635191
TI  - Biochemical and functional changes of rat liver spheroids during spheroid
      formation and maintenance in culture: II. nitric oxide synthesis and related
      changes.
AB  - Liver cells isolated from intact tissue can reaggregate to form three
      dimensional, multicellular spheroids in vitro. During this process, cells undergo
      a histological and environmental change. How cells respond biochemically to this
      change has not been studied in detail previously. We have investigated some
      biochemical changes in rat liver cells during the formation and maintenance of
      spheroids. Liver cells were isolated from male Sprague rats and spheroids
      cultured by a gyrotatory-mediated method. Liver cells were shown to respond to
      the isolation procedure and the formation of spheroids triggered histological
      environmental changes that increased arginine uptake, nitric oxide (NO) and urea
      syntheses, as well as raised levels of GSH, GSSG, glutamic acid and aspartic acid
      secretion within the first couple of days after cell isolation. Levels were
      maintained at a relatively stable level in the mature spheroids (>5 days) over
      the 3 week period of observation. P450 1A1 activity was lost in the first 2 days
      and gradually recovered thereafter. This study, for the first time, shows that
      liver cells after isolation and during spheroid formation actively uptake
      arginine and increase NO and urea syntheses. A high level of NO is likely to play
      an important role in modulating a series of biochemical changes in liver cells.
      It is considered that liver cells actively respond to the 'challenge' induced by
      the isolation procedure and subsequent histological environmental changes, and
      biochemical modulation and instability result. The stable cell-cell contacts and
      histological environment in mature spheroids permit and support functional
      recovery and maintenance in vitro. This period of stability permits the use of
      spheroids in toxicity studies to establish acute and chronic paradigms.

PMID- 14635192
TI  - Inositol 1,4,5-trisphosphate receptor (type 1) phosphorylation and modulation by
      Cdc2.
AB  - Calcium (Ca2+) release from the endoplasmic reticulum (ER) controls numerous
      cellular functions including proliferation, and is regulated in part by inositol
      1,4,5-trisphosphate receptors (IP3Rs). IP3Rs are ubiquitously expressed
      intracellular Ca2+-release channels found in many cell types. Although IP3R
      mediated Ca2+ release has been implicated in cellular proliferation, the
      biochemical pathways that modulate intracellular Ca2+ release during cell cycle
      progression are not known. Sequence analysis of IP3R1 reveals the presence of two
      putative phosphorylation sites for cyclin-dependent kinases (cdks). In the
      present study, we show that cdc2/CyB, a critical regulator of eukaryotic cell
      cycle progression, phosphorylates IP3R1 in vitro and in vivo at both Ser(421) and
      Thr(799) and that this phosphorylation increases IP3 binding. Taken together,
      these results indicate that IP3R1 may be a specific target for cdc2/CyB during
      cell cycle progression.

PMID- 14635193
TI  - MAP kinase activation in cells exposed to a 60 Hz electromagnetic field.
AB  - This research provides evidence that mitogen-activated protein kinase or
      extracellular signal-regulated kinase (MAPK/ERK) is activated in HL-60 human
      leukemia cells, MCF-7 human breast cancer cells, and rat fibroblast 3Y1 cells
      exposed to a 60 Hertz (Hz), 1 Gauss (G) electromagnetic field (EMF). The effects
      of EMF exposure were compared to those observed using 12-O-tetradecanoylphorbal
      13-acetate (TPA) treatment. The level of MAPK activation in cells exposed to EMF
      was approximately equivalent to that in cells treated with 0.1-0.5 ng/ml of TPA.
      A role for protein kinase C (PKC) in the process leading to MAPK activation in
      EMF exposed cells is also suggested by the results. MAPK activation is negated by
      an inhibitor to PKCalpha, but not PKCdelta inhibitors, in cells subjected to EMF
      exposure or TPA treatment. Thus, similarities between the effects of EMF exposure
      and TPA treatment are supported by this investigation. This provides a possible
      method for revealing other participants in EMF-cell interaction, since the TPA
      induction pathway is well documented.

PMID- 14635194
TI  - Membrane actions of vitamin D metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3 are
      retained in growth plate cartilage cells from vitamin D receptor knockout mice.
AB  - 1alpha,25(OH)(2)D(3) regulates rat growth plate chondrocytes via nuclear vitamin
      D receptor (1,25-nVDR) and membrane VDR (1,25-mVDR) mechanisms. To assess the
      relationship between the receptors, we examined the membrane response to
      1alpha,25(OH)(2)D(3) in costochondral cartilage cells from wild type VDR(+/+) and
      VDR(-/-) mice, the latter lacking the 1,25-nVDR and exhibiting type II rickets
      and alopecia. Methods were developed for isolation and culture of cells from the
      resting zone (RC) and growth zone (GC, prehypertrophic and upper hypertrophic
      zones) of the costochondral cartilages from wild type and homozygous knockout
      mice. 1alpha,25(OH)(2)D(3) had no effect on [(3)H]-thymidine incorporation in
      VDR(-/-) GC cells, but it increased [(3)H]-thymidine incorporation in VDR(+/+)
      cells. Proteoglycan production was increased in cultures of both VDR(-/-) and
      VDR(+/+) cells, based on [(35)S]-sulfate incorporation. These effects were
      partially blocked by chelerythrine, which is a specific inhibitor of protein
      kinase C (PKC), indicating that PKC-signaling was involved. 1alpha,25(OH)(2)D(3)
      caused a 10-fold increase in PKC specific activity in VDR(-/-), and VDR(+/+) GC
      cells as early as 1 min, supporting this hypothesis. In contrast,
      1alpha,25(OH)(2)D(3) had no effect on PKC activity in RC cells isolated from VDR(
      /-) or VDR(+/+) mice and neither 1beta,25(OH)(2)D(3) nor 24R,25(OH)(2)D(3)
      affected PKC in GC cells from these mice. Phospholipase C (PLC) activity was also
      increased within 1 min in GC chondrocyte cultures treated with
      1alpha,25(OH)(2)D(3). As noted previously for rat growth plate chondrocytes,
      1alpha,25(OH)(2)D(3) mediated its increases in PKC and PLC activities in the VDR(
      /-) GC cells through activation of phospholipase A(2) (PLA(2)). These responses
      to 1alpha,25(OH)(2)D(3) were blocked by antibodies to 1,25-MARRS, which is a
      [(3)H]-1,25(OH)(2)D(3) binding protein identified in chick enterocytes.
      24R,25(OH)(2)D(3) regulated PKC in VDR(-/-) and VDR(+/+) RC cells. Wild type RC
      cells responded to 24R,25(OH)(2)D(3) with an increase in PKC, whereas treatment
      of RC cells from mice lacking a functional 1,25-nVDR caused a time-dependent
      decrease in PKC between 6 and 9 min. 24R,25(OH)(2)D(3) dependent PKC was mediated
      by phospholipase D, but not by PLC, as noted previously for rat RC cells treated
      with 24R,25(OH)(2)D(3). These results provide definitive evidence that there are
      two distinct receptors to 1alpha,25(OH)(2)D(3). 1alpha,25(OH)(2)D(3)-dependent
      regulation of DNA synthesis in GC cells requires the 1,25-nVDR, although other
      physiological responses to the vitamin D metabolite, such as proteoglycan
      sulfation, involve regulation via the 1,25-mVDR.

PMID- 14635195
TI  - RIFLE: a novel ring zinc finger-leucine-rich repeat containing protein, regulates
      select cell adhesion molecules in PC12 cells.
AB  - Cell adhesion molecules play a critical role in cell contacts, whether cell-cell
      or cell-matrix, and are regulated by multiple signaling pathways. In this report,
      we identify a novel ring zinc finger-leucine-rich repeat containing protein
      (RIFLE) and show that RIFLE, expressed in PC12 cells, enhances the Serine
      (Ser)21/9 phosphorylation of glycogen synthase kinase-3alpha/beta (GSK
      3alpha/beta) resulting in the inhibition of GSK-3 kinase activity and increase of
      beta-catenin levels. RIFLE expression also is associated with elevated E-cadherin
      protein levels but not N-cadherin. The regulation of these cell adhesion
      associated molecules by RIFLE is accompanied by a significant increase in cell
      cell and cell-matrix adhesion. Moreover, increase in cell-cell adhesion but not
      cell-matrix adhesion by RIFLE can be mimicked by selective inhibition of GSK-3.
      Our results suggest that RIFLE represents a novel signaling protein that mediates
      components of the Wnt/wingless signaling pathway and cell adhesion in PC12 cells.

PMID- 14635196
TI  - GADD34 induces p53 phosphorylation and p21/WAF1 transcription.
AB  - Recently, others and we have shown that one of the functions of GADD34 is a
      recovery from a shutoff of protein synthesis induced by endoplasmic reticulum
      stress. GADD34 has been shown to induce growth arrest and apoptosis. Main protein
      of apoptosis is p53, especially phosphorylation of p53. And one of the main
      proteins of growth arrest is p21/WAF1. Here we analyzed the effects of GADD34 on
      p53 phosphorylation and p21/WAF1 transcription. Transfected Myc-tagged p53 was
      dose-dependently phosphorylated at Ser15 by increasing the amount of GADD34.
      Transfection of GADD34 also induced the endogenous phosphorylation of p53 and
      enhanced p21 protein expression. Transfection of GADD34 induced p21/WAF1 promoter
      activity. This activity was dependent on p53, because GADD34 transfection to p53
      deficient cells produced only a slight increase of p21/WAF1 promoter activity.
      The p21/WAF1 promoter activity was greatly enhanced by the transfection of p53.
      Both GADD34 and p53 transfection induced much higher p21/WAF1 promoter activity.
      The promoter activity of p21/WAF1 was very low in GADD34 deficient MEF. The
      transfection of GADD34 increased the p21/WAF1 promoter activity in GADD34
      deficient MEF.

PMID- 14635197
TI  - Prediction and classification of protein subcellular location-sequence-order
      effect and pseudo amino acid composition.
AB  - Given a protein sequence, how to identify its subcellular location? With the
      rapid increase in newly found protein sequences entering into databanks, the
      problem has become more and more important because the function of a protein is
      closely correlated with its localization. To practically deal with the challenge,
      a dataset has been established that allows the identification performed among the
      following 14 subcellular locations: (1) cell wall, (2) centriole, (3)
      chloroplast, (4) cytoplasm, (5) cytoskeleton, (6) endoplasmic reticulum, (7)
      extracellular, (8) Golgi apparatus, (9) lysosome, (10) mitochondria, (11)
      nucleus, (12) peroxisome, (13) plasma membrane, and (14) vacuole. Compared with
      the datasets constructed by the previous investigators, the current one
      represents the largest in the scope of localizations covered, and hence many
      proteins which were totally out of picture in the previous treatments, can now be
      investigated. Meanwhile, to enhance the potential and flexibility in taking into
      account the sequence-order effect, the series-mode pseudo-amino-acid-composition
      has been introduced as a representation for a protein. High success rates are
      obtained by the re-substitution test, jackknife test, and independent dataset
      test, respectively. It is anticipated that the current automated method can be
      developed to a high throughput tool for practical usage in both basic research
      and pharmaceutical industry.

PMID- 14635198
TI  - Concentration of a potent calcium oxalate monohydrate crystal growth inhibitor in
      the urine of normal persons and kidney stone patients by ELISA-based assay system
      employing monoclonal antibodies.
AB  - Standardized calcium oxalate monohydrate (COM) crystal growth assay system was
      employed to study the ability of various test samples to influence growth rates
      of COM crystals. The inhibitory activity (IA) of various samples was expressed in
      terms of inhibitory units. Urine samples obtained from normal persons and kidney
      stone patients were found to have IA of 3.18 +/- 0.62 and 1.02 +/- 0.08,
      respectively. A potent inhibitor having molecular weight between 14.2 and 16.2
      kDa was found to be primarily responsible for the differences observed in the
      urinary IAs between normal persons and kidney stone patients. The potent
      inhibitor was found to be tightly associated with a chromophore resembling
      Urobilirubin. An ELISA based assay system, using monoclonal antibodies against
      the above most potent inhibitor confirmed the difference observed in the urinary
      IA between the normal persons and kidney stone patients. This assay system has
      the potential to be routinely used to screen human beings for potential stone
      formers.

PMID- 14635199
TI  - Antisteroidogenic actions of hydrogen peroxide on rat Leydig cells.
AB  - It has been well known that reactive oxygen species (ROS) are produced in the
      steroidogenic pathway and spermatozoa. H2O2, one of ROS produced by spermatozoa,
      appears to be a primary toxic agent. In the present study, we examined the
      effects of H2O2 on the basal and evoked-testosterone release from primary Leydig
      cells, the protein expressions of cytochrome P450 side chain cleavage enzyme
      (P450scc) and steroidogenic acute regulatory (StAR) protein were also
      investigated. Our preparation was found to contain approximately 87% Leydig cells
      and very few macrophages. The results demonstrated that H2O2 (>1 x 10(-4) M)
      significantly inhibited the basal and hCG-stimulated testosterone release. H2O2
      abolished forskolin- or 8-Br-cAMP-evoked testosterone release. In the presence of
      pregnenolone, progesterone, or androstenedione, the inhibitory effect of H2O2 on
      testosterone release was prevented. H2O2 also inhibited pregnenolone production
      in the presence of trilostane (an inhibitor of 3beta-hydroxysteroid
      dehydrogenase), therefore diminished the activity of P450scc in Leydig cells. In
      addition to the inhibition of hormone secretion, H2O2 also regulated
      steroidogenesis by diminishing protein expression of StAR. These results suggest
      that H2O2 acts directly on rat Leydig cells to diminish testosterone production
      by inhibiting P450scc activity and StAR protein expression.

PMID- 14635200
TI  - Runx2/Cbfa1 stimulation by retinoic acid is potentiated by BMP2 signaling through
      interaction with Smad1 on the collagen X promoter in chondrocytes.
AB  - Chondrocyte differentiation is a fundamental process during endochondral
      ossification. Several factors regulate maturation via the activity of downstream
      signaling pathways that target specific transcription factors and regulate
      chondrocyte-specific genes. In this study, we investigated the mechanisms
      involved in the regulation of chick lower sternal chondrocyte maturation upon
      stimulation by retinoic acid (RA) and the bone morphogenetic protein BMP2. RA
      induced Runx2 in lower sternal chondrocyte cultures and over-expression of wild
      type (WT) Runx2 enhanced colX and alkaline phosphatase activity, while over
      expression of dominant negative Runx2 was inhibitory. Furthermore, WT Runx2
      enhanced the effects of both BMP2 and RA on colX expression, while the effects of
      both growth factors were completely blocked in cultures over-expressing dominant
      negative Runx2. Similarly, WT Runx2 enhanced the induction of colX by Smad1.
      Smad1 and Runx2 were found to act cooperatively at the chicken type X collagen
      promoter and elimination of either the putative Smad binding site or Runx2
      binding site eliminated responsiveness to BMP2, RA, or either of the
      transcription factors. Altogether the results show cross talk between the BMP
      associated Smads and Runx2 during chondrocyte differentiation and dependence upon
      both signals for induction of the type X collagen promoter. Factors or signals
      that alter either of these transcription factors regulate the rate of chondrocyte
      differentiation.

PMID- 14635201
TI  - CD52 expression in hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder
      characterized by splenomegaly, pancytopenia, and circulating atypical lymphocytes
      with circumferential cytoplasmic projections. Although uncommon, HCL cases
      refractory to standard therapy occur, and effective alternatives are limited.
      There is evolving literature supporting monoclonal antibody therapy in the
      treatment of B-cell lymphoid malignancies, including anti-CD52 (Campath-1H,
      alemtuzumab). We have examined nine cases of HCL and one case of HCL variant by
      flow cytometry for CD52 expression. All cases expressed CD52 antigen in 92-100%
      of the malignant cells. The demonstration of CD52 antigen expression on HCL cells
      provides the rationale for the use of alemtuzumab in refractory HCL.

PMID- 14635202
TI  - Fibrinolytic activity in multiple myeloma.
AB  - The incidence of thromboembolic events is high as a result of disease, disease
      related complications, and therapy in multiple myeloma (MM). In patients with
      hematologic tumors, impaired fibrinolysis may be present and may contribute to
      the development of thrombotic complications. Therefore, we designed a study to
      investigate fibrinolytic activity in MM. We compared plasma levels of interleukin
      (IL)-6, C-reactive protein (CRP), IL-1beta, IL-11, tissue plasminogen activator
      (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global
      fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects
      (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow
      up period of 7 months in our myeloma group. Results are given as mean (median,
      range). Plasma levels of IL-6 (8.27 +/- 0.74 [9.65, 0.90-13.32] pg/mL versus 2.64
      +/- 0.66 [1.80, 0.10-11.86] pg/mL, P < 0.001), CRP (45.57 +/- 9.92 [21.00, 1.34
      330.00] mg/L versus 1.96 +/- 0.50 [1.05, 0.19-8.03] mg/L, P < 0.001), PAI-1 (7.40
      +/- 0.67 [5.57, 2.40-31.80] IU/mL versus 4.73 +/- 0.65 [3.60, 2.32-11.00] IU/mL,
      P < 0.01), GFC score (1.90 +/- 0.02 [2, 1-3] versus 2.50 +/- 0.14 [3, 1-3], P <
      0.001) were increased compared with controls. In patients with MM, the level of
      IL-6 was positively correlated with CRP (r = 0.66, P < 0.001), IL-1beta (r =
      0.29, P < 0.05), and PAI-1 (r = 0.35, P < 0.01) and negatively correlated with
      GFC (r = -0.37, P < 0.01). CRP level was positively correlated with plasma PAI-1
      level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = -0.44, P <
      0.001). A significant negative correlation between PAI-1 level and GFC (r = 
      0.75, P < 0.001) was also detected. IL-1beta levels were negatively correlated
      with tPA level (r = -0.26, P < 0.05). These results suggest that patients with
      myeloma have a decreased fibrinolytic activity mainly because of increased PAI-1
      activity. In MM, increased PAI-1 activity seems to be related with elevated IL-6
      level. MM should be considered as a hypercoagulable state as a result of both
      increased procoagulant activity and decreased fibrinolytic activity. Achieving a
      plateau by means of conventional chemotherapies does not improve the decreased
      fibrinolytic activity.

PMID- 14635203
TI  - Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis.
AB  - Imatinib mesylate targets the adenosine triphosphate (ATP)-binding sites of the
      protein tyrosine kinase domains associated with Bcr-abl, the platelet-derived
      growth factor (PDGF) and c-kit. In idiopathic myelofibrosis (IMF) PDGF is
      considered to be one of the growth factors responsible for the development of
      bone marrow fibrosis. Recently, it has been shown that imatinib has
      antifibrogenic effect on bone marrow fibrosis in chronic myelogenous leukemia.
      Treatment with imatinib alone in IMF has been associated with significant side
      effects. In this study, the safety and efficacy of imatinib therapy in IMF,
      either administered as a single agent or in combination with hydroxyurea (HU)
      and/or alpha-interferon (IFN-alpha) are evaluated. Eleven patients (median age,
      63 years; range, 33-82 years) with IMF (n = 8) or postpolycythemic myelofibrosis
      (PPMF) (n = 3) were studied All patients had been treated with HU (n = 9) and/or
      IFN (n = 7) before study entry. In all but one patient, treatment with these
      agents was discontinued when imatinib therapy was instituted. One patient
      continued IFN when treatment with imatinib was started. Imatinib was given at a
      dose of 400 mg/day. Nine patients were in an advanced disease phase. The patients
      have been followed for a median period of 2 months (range, 0.5-12 months).
      Treatment with imatinib has been stopped in six patients (55%), because of overt
      side effects (n = 4), recurrence of transitory dizziness and visual defects owing
      to a rising platelet count (n = 1), or the occurrence of an acute subdural
      hemorrhage that was evacuated without neurological deficits (n = 1). In nine
      patients imatinib treatment was followed by a rise in leukocyte and platelet
      counts that required combination with HU or IFN. The combined treatment
      modalities were followed by a rapid decrease in cell counts and were well
      tolerated apart from IFN side effects. A beneficial effect of imatinib was
      documented in three patients. It is concluded that leukocytosis and
      thrombocytosis are seen in most patients with myelofibrosis during treatment with
      imatinib. Combination therapy with HU or IFN seems safe and well tolerated and
      followed by a decrease in disease activity. A subgroup of patients in an early
      disease phase might benefit from imatinib therapy alone.

PMID- 14635204
TI  - Identification of hemochromatosis gene polymorphisms in chronically transfused
      patients with sickle cell disease.
AB  - Three polymorphic gene mutations in the human hemochromatosis (HFE) gene (C282Y,
      H63D, S65C) are associated with non-transfusion-related iron overload in
      Caucasians. More recently, these mutations have also been identified in African
      Americans. However, the prevalence of HFE gene mutations in African-Americans
      with sickle cell disease (SCD) has not been described. The presence of these
      mutations in this population is particularly important, because patients with SCD
      may be placed on chronic red cell transfusion therapy and are thus at further
      risk for iron overload. Thus, we attempted to establish the gene mutation
      prevalence in African-Americans with SCD, to compare this frequency with
      published gene frequencies in African-Americans, and to evaluate their
      significance with regard to transfusion-related iron overload. Eighty-nine
      African-American patients with SCD, all of whom were receiving chronic red cell
      transfusion therapy, were screened by DNA analysis for the three HFE gene
      mutations. Two patients were heterozygous for the C282Y HFE mutation (2.3%), six
      were heterozygous for the H63D mutation (6.8%), none carried the S65C mutation
      (0.0%), and no homozygous or compound heterozygous subjects were identified. The
      prevalence of C282Y and H63D in the SCD population was similar to that observed
      in the general African-American population. In addition, there was no increased
      mutation prevalence when comparing those SCD patients on chronic transfusion
      therapy who had ferritin levels greater than 2,500 ng/mL and those less than
      2,500 ng/mL. This study represents the first identification of the known HFE gene
      mutations by DNA analysis in the SCD population. We conclude that the presence of
      recognized HFE coding region mutations do not seem to have an impact on the
      degree of iron overload in patients with SCD receiving chronic transfusion
      therapy.

PMID- 14635205
TI  - Malignancy in patients with sickle cell disease.
AB  - Malignancy in patients with sickle cell disease (SCD) has been previously
      reported, but the types of cancer and its incidence remain undefined. With the
      advent of hydroxyurea therapy, there is concern about increasing the cancer risk
      for patients with SCD. The International Association of Sickle Cell Nurses and
      Physician Assistants identified 52 cases of cancer (49 patients) among 16,613
      patients with SCD followed at 52 institutions. The median age at malignancy
      diagnosis was 34 years (range, 14 months-62 years). Twenty-one cases (40%)
      occurred in pediatric patients, primarily leukemia (n = 7) or Wilms' tumor (n =
      5), with 15 children surviving. Most adults had solid tumors, especially
      carcinomas, and only nine were known to be alive. Three patients received
      hydroxyurea before the diagnosis of malignancy. These data provide essential
      baseline information for the accurate interpretation of future reports of
      malignancy in patients with SCD, especially those receiving hydroxyurea therapy.

PMID- 14635206
TI  - MYH9 spectrum of autosomal-dominant giant platelet syndromes: unexpected
      association with fibulin-1 variant-D inactivation.
AB  - The autosomal-dominant giant platelet syndromes (Fechtner, Epstein, and Sebastian
      platelet syndromes and May-Hegglin anomaly) represent a group of disorders
      characterized by variable degrees of macrothrombocytopenia with further
      combinations of neutrophil inclusion bodies and Alport-like syndrome
      manifestations, namely, deafness, renal disease, and eye abnormalities. The
      disease-causing gene of these giant platelet syndromes was previously mapped by
      us to chromosome 22. Following their successful mapping, these syndromes were
      shown to represent a broad phenotypic spectrum of disorders caused by different
      mutations in the nonmuscle myosin heavy chain 9 gene (MYH9). In this study, we
      examined the potential role of another gene, fibulin-1, encoding an extracellular
      matrix protein as a disease modifier. Eight unrelated families with autosomal
      dominant giant platelet syndromes were studied for DNA sequence mutations and
      expression of the four fibulin-1 splice variants (A-D). A mutation in the splice
      acceptor site of fibulin-1 exon 19 was found in affected individuals of the
      Israeli Fechtner family, whereas no MYH9 mutations were identified. Unexpectedly,
      fibulin-1 variant D expression was absent in affected individuals from all eight
      families and coupled with expression of a putative antisense RNA. Transfection of
      the putative antisense RNA into H1299 cells abolished variant D expression. Based
      on the observation that only affected individuals lack variant D expression and
      demonstrate antisense RNA overexpression, we suggest that these autosomal
      dominant giant platelet syndromes are associated, and may be modified, by
      aberrant antisense gene regulation of the fibulin-1 gene.

PMID- 14635207
TI  - Refractory autoimmune thrombocytopenic purpura: responses to treatment with a
      recombinant antibody to lymphocyte membrane antigen CD20 (rituximab).
AB  - "Refractory" autoimmune thrombocytopenia represents a life-threatening condition,
      having failed to respond to a variety of therapeutic measures. We report a series
      of cases, all failing splenectomy and multiple therapeutic programs, including,
      in two patients, marrow transplant. Five of the six cases reported responded to a
      recombinant antibody to the lymphocyte membrane antigen CD20 (rituximab), an
      agent commonly employed in the treatment of non-Hodgkin's lymphoma. Our
      experiences over a period of 4 years are documented. The results support the use
      of this product, rituximab, in the treatment of patients with autoimmune
      thrombocytopenia who have not attained a hemostatically effective platelet count
      following splenectomy and require a continuing therapeutic management program.

PMID- 14635208
TI  - Chronic myelogenous leukemia with e13a3 (b2a3) type of BCR-ABL transcript having
      a DNA breakpoint between ABL exons a2 and a3.
AB  - We describe a patient with chronic myelogenous leukemia (CML), in whom the DNA
      breakpoint in the BCR-ABL fusion gene was determined to result in a rare e13a3
      (b2a3) transcript. The breakpoint in BCR was intron 13, which was 30 bp
      downstream from exon 13, and the breakpoint in ABL was intron 2, and was 46 bp
      downstream from exon a2. This case conforms to the mechanism of DNA breakage
      occurring within ABL intron 2, but not at 5' to ABL exon a2. With our review of
      this case and the literature, it seems that CML with the BCR-a3 fusion product is
      associated with a low proportion of circulating immature cells, mild or lack of
      splenomegaly, slow progressiveness, rather resistance to IFN-alpha, and good
      response to imatinib mesylate. This is the first report of BCR-a3-type CML in
      which the exact DNA breakpoint was identified and located between exons a2 and a3
      of the ABL gene.

PMID- 14635209
TI  - Successful treatment of acquired pure red cell aplasia (PRCA) by allogeneic
      peripheral blood stem cell transplantation.
AB  - A 37-year-old male was treated successfully by peripheral blood stem cell
      transplantation (PBSCT) from his HLA-identical sister for refractory acquired
      pure red cell aplasia (PRCA). The conditioning regimen was cyclophosphamide 50
      mg/kg/day for 4 days plus TBI 300 cGy in a single fraction. Absolute neutrophil
      count (ANC) >500/microl and platelet counts >20,000/microl were achieved 8 days
      after PBSCT without transfusion. Chimerism study on day 218 revealed full donor
      chimerism. The hemoglobin level was stable around 12-13 g/dl with normal
      leukocyte and platelet counts after PBSCT during a long follow-up period. From
      this case, PBSCT should be considered for patients with refractory acquired PRCA
      with an HLA-identical donor.

PMID- 14635210
TI  - Acute renal failure after intravenous anti-D immune globulin in an adult with
      immune thrombocytopenic purpura.
AB  - Intravenous anti-D immune globulin (anti-D IGIV) is indicated for the treatment
      of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are
      Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis
      (IVH) and acute renal failure (ARF) after anti-D IGIV. We report the first adult
      patient with ITP who required and received dialysis after IVH and ARF
      complicating treatment with anti-D IGIV. Whether the transfusion of 2 units of
      Rh(D)-positive red cells, indicated for the resulting anemia, exacerbated the IVH
      and renal failure is unclear. Three weeks after the administration of anti-D IGIV
      (13 days after two hemodialysis treatments), the patient's renal function had
      returned to normal. This case highlights the infrequent but potentially serious
      side effects of anti-D IGIV and the need to monitor a patient's renal function
      closely if there is evidence of IVH after infusion of anti-D IGIV. If red cell
      transfusion is indicated, we recommend the use of Rh(D)-negative red cell
      products.

PMID- 14635211
TI  - First observation of homozygous hemoglobin hamadan (B 56 (D7) GLY-ARG) and beta
      thalassemia (-29 G>A)- hemoglobin Hamadan combination in a Turkish family.
AB  - During screening surveys for beta thalassemia and abnormal hemoglobins in Mugla,
      a city located in the Aegean Region of Turkey, a hemoglobin variant was detected
      in two large families residing in two neigboring cities (i.e., Mugla and Aydin)
      without any clinical signs. Further analysis of the variant revealed it as Hb
      Hamadan (B 56 (D7) GLY-ARG). Family screening revealed the father of the
      propositus as homozygote Hb Hamadan. The grandfather of the index case was
      detected as combination of Hb Hamadan with beta thalassemia. The beta thalassemia
      carrier had a promotor mutation at -29 G>A, which is also a novel mutation.
      Furthermore, we described a simple and rapid restriction enzyme digestion
      protocol (Hha I) for the verification of Hb Hamadan. The clinical and hematologic
      data of the index case and his father showed that neither homozygous Hb Hamadan
      nor combination with beta thalassemia has clinical importance. This is also
      important especially from the prenatal diagnosis point of view.

PMID- 14635212
TI  - Treatment of postrenal transplantation lymphoproliferative disease manifesting as
      plasmacytoma with nonmyeloablative hematopoietic stem cell transplantation from
      the same kidney donor.
AB  - Posttransplantation lymphoproliferative disease (PTLD) presenting as an Epstein
      Barr-virus (EBV)-related nasal plasmacytoma developed in a renal-allograft
      recipient 13 years after transplantation. Systemic dissemination occurred despite
      immunosuppression withdrawal, surgery, irradiation, and chemotherapy. A
      nonmyeloablative hematopoietic-stem-cell-transplantation (HSCT) with peripheral
      blood HSC from the kidney donor was performed. With the onset of graft-versus
      host disease, resolution of the systemic disease was demonstrated clinically and
      molecularly by serial quantification of plasma EBV-DNA. Isolated relapse occurred
      in the central nervous system (CNS), a known tumour sanctuary site, ultimately
      leading to death. Nonmyeloablative HSCT might be considered a cellular therapy
      for PTLD, but possible CNS relapse must be effectively tackled.

PMID- 14635213
TI  - Extranodal diffuse follicular center lymphoma mimicking mantle cell lymphoma of
      the intestine.
AB  - We report a case of diffuse follicular center lymphoma (FCL), which is a
      morphological variant of follicular lymphoma, resembling multiple lymphomatous
      polyposis (mantle cell lymphoma of the intestine). The patient was a 48-year-old
      Japanese man who was found, by colonoscopy, to have numerous small polypoid
      lesions along the entire large intestine. Abdominal computed tomography revealed
      hepatosplenomegaly and enlargement of multiple mesenteric lymph nodes.
      Histologically, the lesion was characterized by diffuse proliferation of small-
      to medium-sized lymphocytes with cleaved nuclei in the mucosa and submucosa.
      Immunohistochemical studies showed that the tumor cells were CD20+, CD10+, BCL
      2+, CD5-, surface IgM-, and cyclin D1-. Moreover, a cytogenetic study showed a
      translocation at (14;18)(q32;q21). Finally, this case was diagnosed as diffuse
      FCL, although the tumor was mimicking mantle cell lymphoma.

PMID- 14635214
TI  - Pegylated-interferon induced severe bone marrow hypoplasia in a patient with
      multiple myeloma receiving thalidomide.

PMID- 14635215
TI  - Estrogen and cognition: applying preclinical findings to clinical perspectives.
AB  - The effects of hormone replacement therapy on brain aging and cognition are an
      important public health issue, which, despite much research and debate, has not
      yet been resolved. In this Mini-Review, we describe how much of the clinical
      literature takes on new meaning when interpreted in light of recent preclinical
      data. We predict, based on these data, that hormone replacement therapy will in
      fact provide substantial benefit with respect to age-related cognitive decline,
      provided that therapy is administered in an appropriate regimen and is initiated
      within a window of time following the loss of ovarian function. The application
      of these data to recent clinical findings is discussed.

PMID- 14635216
TI  - Mild carbon monoxide exposure and auditory function in the developing rat.
AB  - We have examined the influence of chronic mild exposure to carbon monoxide (CO)
      on cognitive (learning) and auditory function in the developing rat. We have
      demonstrated that the auditory pathway is compromised at exposures less than 50
      ppm, whereas learning was not influenced at 100 ppm. Artificially reared rat pups
      were exposed to CO during the brain growth spurt and onset of myelination.
      Spatial learning was assessed using the Morris Water Maze and three tests of
      auditory function: (1) auditory brainstem conduction times; (2) the amplitude of
      the eighth nerve's action potential; and (3) otoacoustic emissions carried out on
      rat pups (age 22- 24 days). The pups were gastrostomy-reared on a rat milk
      substitute and chronically exposed to CO at discrete concentrations in the range
      of 12-100 ppm from 6 days of age to post-weaning at 21-23 days of age. We found
      no difference in auditory brainstem conduction times at all CO concentrations in
      comparison to non-exposed controls. There was a difference in otoacoustic
      emissions for test and controls at CO concentrations of 50 ppm but not at lower
      concentrations. There was a consistent attenuation of the amplitude of the eighth
      nerve's action potential, even at the lowest CO exposure examined. The
      attenuation of the amplitude of the action potential of the eighth nerve at 50
      ppm carbon monoxide exposure did not completely recover by 73 days of age. We
      conclude that prolonged mild exposure to carbon monoxide during development
      causes measurable functional changes at the level of the eighth cranial nerve.

PMID- 14635217
TI  - Mild carbon monoxide exposure impairs the developing auditory system of the rat.
AB  - The object of this study was to determine if chronic exposure to mild
      concentrations of CO in air caused changes in the integrity of the inferior
      colliculus during the most active period of synaptogenesis/auditory development.
      We examined all subregions of the inferior colliculus (IC) of rats by
      immunocytochemical approaches after pups were exposed chronically to CO
      concentrations of, 0, 12.5, 25, and 50 ppm in air starting at Day 8 through 20-22
      days of age. Mother-reared pups were compared to the gastrostomy-reared pups with
      or without CO exposure for basal neural activity, using c-Fos immunoreactivity as
      a marker. Half the rats were examined at 27 days of age, 5 days after the end of
      CO exposure, and the other half were examined 50 days later at 75-77 days of age.
      In the central nucleus of the IC, the number of cells expressing a basal level of
      c-Fos was decreased significantly in the CO-exposed animals when compared to
      controls; however, there was little or no difference in the number of cells
      expressing c-Fos in the other subregions of the IC. We conclude that the central
      nucleus of the inferior colliculus is affected selectively by mild CO exposure
      (0.0012% in air) and that this reduction in neuronal activity persists into
      adulthood.

PMID- 14635218
TI  - Mild carbon monoxide exposure diminishes selectively the integrity of the cochlea
      of the developing rat.
AB  - Rat pups were chronically exposed to carbon monoxide (CO) concentrations (12 or
      25 ppm) in air starting at day 8, through 22 days of age, to examine the changes
      in the peripheral auditory system. Gastrostomy-reared rat pups, with or without
      CO exposure, were used and compared with mother-reared pups. The organ of Corti
      and the neurons of the spiral ganglion were analyzed for their morphology by
      using immunochemical and histological techniques. The inner and outer hair cells
      in the organ of Corti of animals exposed to 12 and 25 ppm CO were not different
      from the controls. However, at 25 ppm CO exposure, the nerve terminals
      innervating the inner hair cells were swollen. The somata of neurons in the
      spiral ganglion showed mild changes in the cytoplasm, and signs of mild
      vacuolization were observed in myelin covering their central processes.
      Synaptophysin, a marker for synaptic vesicles, and choline acetyltransferase, a
      marker for cholinergic terminals, showed no difference in immunoreactivity in CO
      exposed animals at 12 and at 25 ppm when compared with their age-matched
      controls. Also, Na(+)K(+) ATPase immunoreactivity patterns were normal compared
      with controls. Three enzymes were significantly reduced at the 25 ppm CO
      exposure: Cytochrome oxidase, NADH-TR, and calcium ATPase were decreased in both
      the organ of Corti and the neurons of the spiral ganglion, and decreased
      immunostaining for the neurofilament and myelin basic proteins was found. We
      conclude that components of the cochlea are selectively affected by mild chronic
      CO exposure during development.

PMID- 14635219
TI  - Inhibition of NMDA receptors induces delayed neuronal maturation and sustained
      proliferation of progenitor cells during neocortical development.
AB  - To elucidate the role of N-methyl-D-aspartate (NMDA) receptors during the early
      stage of cerebral neocortical development, we investigated the effect of an NMDA
      receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-APV), on cell
      migration and proliferation in slice cultures and dissociated primary cultures
      prepared from rat cerebral neocortex at embryonic Day 17. Pulse-labeling
      experiments with 5-bromo-2'-deoxyuridine (BrdU) showed that chronic exposure to D
      APV in slices delayed neuronal migration. Calcium imaging experiments revealed
      that functional NMDA receptors were expressed in neurons and the treatment with D
      APV delayed neuronal maturation judging from the subunit composition of NMDA
      receptor subtypes. The results using pulse-labeling with BrdU indicated that
      exposure to D-APV for 3 days induced a clear increase in the number of
      proliferating progenitor cells in the ventricular zone in neocortical slices.
      Exposure to D-APV in primary cultures also increased the proliferation of
      progenitor cells. The effect of D-APV on progenitor cell proliferation was
      possibly mediated through neuronal cells. To elucidate the mechanism of enhanced
      progenitor cell proliferation induced by D-APV, we investigated expression of
      Hes1 and Hes5 mRNA in the ventricular zone of neocortical slices by reverse
      transcription-polymerase chain reaction. Tissue exposed to D-APV for 3 days
      showed higher expression of Hes1 and Hes5 mRNA than did unexposed control tissue.
      These results suggest that NMDA receptors expressed in neurons function in
      neuronal migration and maturation and in the proliferation of progenitor cells.

PMID- 14635220
TI  - Effect of excess extracellular glutamate on dendrite growth from cerebral
      cortical neurons at 3 days in vitro: Involvement of NMDA receptors.
AB  - Glutamate is an important regulator of dendrite development; however, during
      cerebral ischemia, massive glutamate release can lead to neurodegeneration and
      death. An early consequence of glutamate excitotoxicity is dendrite injury, which
      often precedes cell death. We examined the effect of glutamate on dendrite growth
      from embryonic day 18 (E18) mouse cortical neurons grown for 3 days in vitro
      (DIV) and immunolabeled with anti-microtubule-associated protein (MAP)2 and anti
      neurofilament (NF)-H, to identify dendrites and axons, respectively. Cortical
      neurons exposed to excess extracellular glutamate (100 microM) displayed reduced
      dendrite growth, which occurred in the absence of cell death. This effect was
      mimicked by the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA)
      and blocked by the ionotropic glutamate receptor antagonist kynurenic acid and
      the NMDA receptor-specific antagonist MK-801. The non-NMDA receptor agonist AMPA,
      however, did not affect process growth. Neither NMDA nor AMPA influenced neuron
      survival. Immunolabeling and Western blot analysis of NMDA receptors using
      antibodies against the NR1 subunit, demonstrated that immature cortical neurons
      used in this study, express NMDA receptors. These results suggest that excess
      glutamate decreases dendrite growth through a mechanism resulting from NMDA
      receptor subclass activation. Furthermore, these data support the possibility
      that excess glutamate activation of NMDA receptors mediate both cell death in
      mature neurons and the inhibitory effect of excess glutamate on dendrite growth
      in immature neurons or in the absence of cell death.

PMID- 14635221
TI  - GeneChip analysis of hippocampal gene expression profiles of short- and long
      attack-latency mice: technical and biological implications.
AB  - To gain insight into the molecular mechanisms underlying the behavioral
      differences between two mouse lines genetically selected for long and short
      attack latency (LAL and SAL mice, respectively), we have recently applied the
      large-scale gene expression profiling method known as serial analysis of gene
      expression (SAGE) to generate hippocampal gene expression profiles of these mice.
      The aim of the present study is to extend and validate the SAGE expression
      profile of hippocampi of LAL and SAL mice using GeneChips (Affymetrix, Santa
      Clara, CA; one array per mouse, n = 5 per mouse line). As was the case with SAGE,
      GeneChips detect only medium- to high-abundance genes in the hippocampus.
      Extensive analysis of GeneChip data using very stringent parameters shows
      differential expression of 122 genes, all except one of which were expressed at
      higher levels in LAL mice (P < 0.01). As predicted by SAGE, our data indicate
      higher expression of several cytoskeleton genes in LAL mice, suggesting longer
      axonal and dendritic projections in the hippocampus of these mice. This is
      consistent with our tentative model, in which the behavioral differences between
      LAL and SAL mice may be related to structural differences in the hippocampus. In
      addition, a group of 76 genes with diverse biological function and 46 expressed
      sequence tags (ESTs) were all expressed at higher levels in LAL mice. A novel
      finding in this study was the significantly lower expression of only a single
      gene, growth arrest-specific gene (gas5), in LAL mice. As gas5 does not encode a
      protein but several small nuclear RNAs, our data suggest that small RNAs may
      contribute to the molecular mechanisms underlying the extreme behavioral
      differences between LAL and SAL mice.

PMID- 14635222
TI  - Transcriptional regulation through glutamate receptors: Involvement of tyrosine
      kinases.
AB  - Glutamate receptors play a key role in neuronal plasticity, learning and memory,
      and in several neuropathologies. Short-term and long-term changes in synaptic
      efficacy are triggered by glutamate. Although an enhanced glutamate-dependent
      tyrosine phosphorylation has been described in several systems, its role in
      membrane-to-nuclei signaling is unclear. Taking advantage of the fact that the
      gene encoding the chick kainate-binding protein undergoes a glutamate-dependent
      transcriptional regulation via an activator protein-1 (AP-1) site, we evaluated
      the involvement of tyrosine kinases in this process. We describe here the
      participation of receptor and non-receptor tyrosine kinases in the signaling
      cascade triggered by glutamate. Our results suggest that in Bergmann glia cells,
      glutamate receptors transactivate receptor tyrosine kinases, favoring the idea of
      a complex network of signals activated by this excitatory neurotransmitter that
      results in regulation of gene expression.

PMID- 14635223
TI  - Role of phosphatidylinositol 3-kinase in neuronal survival and axonal outgrowth
      of adult mouse dorsal root ganglia explants.
AB  - Adult ganglionic peripheral neurons have lost dependence on target-derived
      neurotrophin signaling for survival and regeneration after injury. To understand
      the mechanisms required to sustain such processes at maturity, we are studying
      neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia (DRG)
      explants. We have here examined the role of phosphatidylinositol 3-kinase (PI3-K)
      activity. Both neuronal survival and axonal outgrowth of spontaneously growing
      preparations were decreased significantly by the PI3-K inhibitor LY294002 as was
      the increased outgrowth caused by nerve growth factor or glial cell line-derived
      factor. Inhibition of PI3-K activity promoted neuronal cell death to the same
      extent in the presence as in the absence of a growth factor, whereas inhibition
      of mitogen-activated protein kinase, MAPK, lacked effect. Using a
      compartmentalized system, it could be shown that only axonal outgrowth was
      decreased when the outgrowth region only was exposed to LY294002. Already-formed
      growth cones showed morphological changes within 5-10 min after exposure to
      LY294002. Akt (PKB) is one downstream effector of PI3-K. Immunofluorescence
      revealed the presence of activated Akt in DRG cell bodies and in axonal growth
      cones. Immunoreactivity was decreased by PI3-K inhibition. The results suggest
      that Akt is constitutively active in adult DRG neurons, and that PI3-K mediated
      processes are involved in neuronal survival of one or more DRG neuronal
      subpopulations and also in axonal elongation. The possible significance of Akt
      signaling for these effects is discussed.

PMID- 14635224
TI  - Protective effects of extracellular glutathione against Zn2+-induced cell death
      in vitro and in vivo.
AB  - The central nervous system reserves high concentrations of free Zn(2+) in certain
      excitatory synaptic vesicles. In pathological conditions such as transient
      cerebral ischemia, traumatic brain injury, and kainic acid (KA)-induced seizure,
      free Zn(2+) is released in excess at synapses, which causes neuronal and glial
      death. We report here that glutathione (GSH) can be used as an effective means
      for protection of neural cells from Zn(2+)-induced cell death in vitro and in
      vivo. Chronic treatment with 35 microM Zn(2+) led to death of primary cortical
      neurons and primary astrocytes. The Zn(2+) toxicity of cortical neurons was
      partially protected by 1 mM of GSH, whereas the Zn(2+) toxicity of primary
      astrocyte cultures was blocked completely by 100 microM of GSH. To evaluate the
      beneficial effects of GSH in vivo, an excitotoxin-induced neural cell death model
      was established by intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2
      microg) KA, which produced selective neuronal death, especially in CA1 and CA3
      hippocampal regions. The i.c.v. co-injection of 200 pmol of GSH significantly
      attenuated KA-induced neuronal cell death and reactive gliosis in hippocampus.
      The results of this study suggest the contribution of Zn(2+) in the excitotoxin
      induced neural cell death model and a potential value of GSH as a therapeutic
      means against Zn(2+)-induced pathogenesis in brain.

PMID- 14635225
TI  - Differential regulation of polysialyltransferase expression during hippocampus
      development: Implications for neuronal survival.
AB  - Polysialyltransferases ST8SiaII/STX and ST8SiaIV/PST add polysialic acid (PSA) to
      the neural cell adhesion molecule (NCAM). Surface-located PSA is involved in cell
      cell interactions participating in structural and functional plasticity of
      neuronal circuits. This study was undertaken to investigate the
      polysialyltransferase regulation pattern during hippocampal development.
      Polysialyltransferase expression levels analyzed by real-time RT-PCR indicated
      that ST8SiaII/STX mRNA is markedly down-regulated in vivo, decreasing abruptly at
      about the first week of postnatal development. ST8SiaII/STX mRNA is also down
      regulated in hippocampal cells in culture, accompanying the morphological
      differentiation of neuronal interconnectivity. In contrast, ST8SiaIV/PST levels
      remain comparatively low during hippocampus ontogeny. Immunolabeling of primary
      hippocampal culture assays demonstrated that PSA expression parallels
      ST8SiaII/STX mRNA levels. In comparison, polysialyltransferase mRNA levels are
      not regulated in neuroblastoma cells during their proliferation. Sequence
      analysis of the 3'-untranslated region of ST8SiaII/STX cDNA indicated putative
      regulatory motifs. This information and the observed changes in mRNA half-life
      during development suggest that ST8SiaII/STX might be also regulated at the
      posttranscriptional level. To understand the reasons for the tight control of
      ST8SiaII/STX expression during development, we overexpressed the enzyme in
      hippocampal primary cultures by transfection. Overexpression of ST8SiaII/STX wild
      type as well as of a mutant lacking enzymatic activity affected neuronal
      viability, leading to cell death. However, this phenomenon was abolished by a
      double mutation in the ST8SiaII/STX that prevents formation of its three
      dimentional structure. Interestingly, the overexpressed polysialyltransferase
      accumulates not only in the perinuclear region but also in the plasma membrane.
      Thus, overexpression of an ST8SiaII/STX that conserves its structure leads to
      abnormal accumulation of the protein, probably on the neuronal surface, affecting
      cell viability. This result explains the importance of an accurate regulation of
      polysialyltransferase expression during development.

PMID- 14635226
TI  - Neuroprotective effect of adenine on purkinje cell survival in rat cerebellar
      primary cultures.
AB  - Although adenosine or ATP is known to control various physiological functions in
      the brain, including synaptic transmission, neuronal cell death, and neurite
      outgrowth via P1 or P2 purinergic receptors in the nervous system, little is
      known about the functions of many other purine derivatives. We examined the
      effects of various purines on survival in the cerebellar cortex of Purkinje cells
      with large cell bodies and highly branched dendrites, and it was found that some
      purine and pyrimidine derivatives influence Purkinje cell survival. Treatment
      with adenine, guanine, guanosine, guanine nucleotides, and uracil nucleotides
      protected Purkinje cells from cell death in the cerebellar primary cultures.
      Among the effective compounds, adenine had the most potent survival activities on
      Purkinje cells. Other adenine-based purines such as adenosine, AMP, ADP, and ATP
      did not promote Purkinje cell survival. Furthermore, metabolic inhibitors of
      adenine had no effect on the protective ability of adenine for Purkinje cells,
      suggesting that adenine itself, not adenine metabolites, maintains Purkinje cell
      survival. These results suggest that adenine is involved in the control of
      Purkinje cell survival in cerebellar primary cultures via a novel adenine
      dependent mechanism.

PMID- 14635227
TI  - Hepatocyte growth factor stimulates cell motility in cultures of the striatal
      progenitor cells ST14A.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a growth factor with
      pleiotropic effects on different cell types. It acts as a mitogen and motility
      factor for many epithelial cells. HGF/SF and its receptor Met are present in the
      developing and adult mammalian brain and control neuritogenesis of sympathetic
      and sensory neurons. We report that the striatal progenitor ST14A cells express
      the Met receptor, which is activated after binding with HGF/SF. The interaction
      between Met and HGF/SF triggers a signaling cascade that leads to increased
      levels of c-Jun, c-Fos, and Egr-1 proteins, in agreement with data reported on
      the signaling events evoked by HGF in other cellular types. We also studied the
      effects of the exposure of ST14A cells to HGF/SF. By time-lapse photography, we
      observed that a 24-hr treatment with 50 ng/ml HGF/SF induced modification in cell
      morphology, with a decrease in cell-cell interactions and increase of cell
      motility. In contrast, no effect on cell proliferation was observed. To
      investigate which intracellular pathway is primarily involved we used PD98059 and
      LY294002, two specific inhibitors of mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAP-kinase/ERK-kinase) and
      phosphoinositide 3-OH kinase (PI3-K), respectively. Cell motility in HGF/SF
      treated cultures was inhibited by LY294002 but not by PD98059, suggesting that
      PI3-K plays a key role in mediating the HGF/SF-induced dissociation of ST14A
      cells. Previous evidence of HGF stimulation of motility in nervous system has
      been obtained on postmitotic neurons, which have already acquired their
      specificity. Data reported here of a motogenic response of ST14A cell line, which
      displays properties of neuronal progenitors, seem of interest because they
      suggest that HGF could play a role in very early steps of neurogenesis.

PMID- 14635228
TI  - Expression of gangliosides in an immortalized neural progenitor/stem cell line.
AB  - Glycosphingolipids (GSLs) are known to play important roles in cellular growth
      and differentiation in the nervous system. The change in expression of
      gangliosides is correlated with crucial developmental events and is
      evolutionarily conserved among many vertebrate species. The emergence of neural
      progenitors represents a crucial step in neural development, but little is known
      about the exact composition and subcellular localization of gangliosides in
      neural progenitor cells. The C17.2 cell line was derived after v-myc
      transformation of neural progenitor cells isolated from neonatal mouse cerebellar
      cortex. The developmental potential of C17.2 cells is similar to that of
      endogenous neural progenitor/stem cells in that they are multipotential and
      capable of differentiating into all neural cell types. We characterized the GSL
      composition of C17.2 cells and found the presence of only a-series gangliosides.
      Subcellular localization studies revealed that GM1 and GD1a are localized mainly
      on the plasma membrane and partly in the cytoplasm, both as punctate clusters.
      Reverse transcription-polymerase chain reaction revealed the absence of ST-II
      transcripts in C17 cells, which most likely accounts for the lack of expression
      of b- and c-series complex gangliosides in this cell line. These data suggest
      that the divergence in ganglioside expression in C17.2 cells is regulated at the
      transcriptional level.

PMID- 14635229
TI  - Loss of pro-apoptotic BH3-only Bcl-2 family member Bim does not protect mutant
      Lurcher mice from neurodegeneration.
AB  - Lurcher (lc) mice have a semi-dominant mutation in the gene encoding the delta2
      glutamate receptor (GRID2). The resulting constitutive activity of this receptor
      in heterozygous +/lc (grid(+/lc)) and homozygous (grid(lc/lc)) mice leads to the
      death of all cerebellar Purkinje cells and most afferent granule neurons. Some
      studies have indicated that the death of Purkinje cells occurs by apoptosis, and
      the secondary loss of granule neurons has been shown to require the pro-apoptotic
      Bcl-2 family member Bax. The BH3-only protein Bim has been shown to contribute to
      cytokine withdrawal-induced apoptosis of sympathetic neurons and to be
      responsible for the kidney degeneration in mice lacking the pro-survival protein
      Bcl-2. Because Bim is expressed strongly in cerebellar Purkinje cells, we have
      examined whether it has a role in their death in mutant Lurcher mice. Our studies
      show that Bim deficiency does not modify the Lurcher phenotype, ruling out an
      indispensable role for Bim in this neurodegenerative disease.

PMID- 14635230
TI  - An antisense construct reduces N-methyl-D-aspartate receptor 2A expression and
      receptor-mediated excitotoxicity as determined by a novel flow cytometric
      approach.
AB  - The N-methyl-D-aspartate receptor (NMDAR) is a major neurotransmitter receptor in
      the central nervous system (CNS), with functional roles in learning, memory, and
      sensation. Several mechanisms potentiate NMDARs, and NMDAR hyperexcitability
      plays pathophysiological roles in many conditions, such as neurodegenerative
      disease, ischemia, and chronic conditions arising from spinal cord injury.
      Previous research suggests that the NR2A subunit of the receptor contributes to
      NMDAR excitotoxicity in heterologous cells and in neurons in vivo. To investigate
      the role of NR2A in NMDAR excitotoxicity, we have developed a system based on
      flow cytometry that allows rapid evaluation of the effect of antisense constructs
      on protein expression and channel function. The enhanced yellow fluorescent
      protein (EYFP) was fused to obligatory NMDAR subunits, allowing expression to be
      monitored in living cultured cells. An NR2A antisense construct, asNR2A,
      specifically and effectively reduced NR2A-EYFP expression. NR1 and NR2A fusion
      proteins formed functional, excitotoxic channels upon co-expression. The asNR2A
      RNA significantly reduced NMDAR excitotoxicity when NR2A levels were limiting for
      channel formation. Using our assay system, further optimization can be achieved
      rapidly. The asNR2A construct and the assays developed for this study can be used
      to provide insights into NMDAR biology and disease.

PMID- 14635231
TI  - Adenoviral-mediated expression of functional Na+ channel beta1 subunits tagged
      with a yellow fluorescent protein.
AB  - Voltage-gated sodium (Na(+)) channels typically contain a pore-forming alpha
      subunit and one or two auxiliary beta subunits. Although initial characterization
      of known alpha and beta subunits has been facilitated by expression in
      heterologous cells, to understand fully the differences between individual
      subunits and the functional consequences of selective subunit expression, there
      is a need to acutely manipulate expression in cells that endogenously express
      Na(+) channels. To this end, we have constructed a recombinant adenovirus
      containing a cDNA for a mouse Na(+) channel beta1 subunit with a yellow
      fluorescent protein fused to its C-terminus (Ad-beta1-EYFP), and with
      fluorescence microscopy detected beta1-EYFP expression in primary cerebellar
      neurons and Chinese hamster ovary (CHO) cells upon transduction with this
      adenovirus, including expression in the plasma membrane. Consistent with this,
      patch clamp recordings confirmed that Na(+) currents in CHO cells expressing
      mouse Na(v)1.4 alpha subunits were appropriately modified by the viral-mediated
      expression of beta1-EYFP subunits. The results demonstrate that adenoviral
      mediated gene delivery can be used effectively to express epitope-tagged Na(+)
      channel subunits with properties similar to wild-type subunits, and suggest that
      Ad-beta1-EYFP will be a useful reagent for investigating Na(+) channels in a
      variety of excitable cell types, including neurons.

PMID- 14635232
TI  - Introduction: epidemiologic research on occupational health in women.

PMID- 14635233
TI  - Occupational cancer among women: where have we been and where are we going?
AB  - Studies of occupational exposures have been a fruitful area of research for
      identifying carcinogens. Some of the early observations, such as increased risk
      of breast cancer among nuns and bone cancer among radium dial workers, were made
      among women. Recent research on cancer among women has shown increased risks of
      cancer in many industries and occupations. Estimates that 1% of cancer among
      women is attributable to occupation are based on research conducted mainly in the
      1970s among men in developed countries. These studies do not reflect the dramatic
      changes in the participation of women in the workplace or the patterns of
      employment of women in developing countries. The proportion of women in the paid
      workforce, the amounts and types of unpaid labor, the distribution of women by
      economy sector, the scale of the workplaces, the allowable exposure levels in the
      workplace, and implementation of controls have changed over time and vary
      internationally. Occupational cancer researchers need to expand their focus on
      women, increase activities in developing countries, include newly created
      industries, use sophisticated exposure assessment methods, and, where
      appropriate, incorporate molecular epidemiologic techniques to discover new
      occupational carcinogens and to identify where better control measures are
      needed.

PMID- 14635234
TI  - Exposure assessment in epidemiology: does gender matter?
AB  - BACKGROUND: The pathway from potential hazards in the work environment to the
      measurement or estimation of personal exposure for epidemiologic studies
      comprises many steps, each of which can be influenced by factors that may or may
      not differ by gender. This article explores this pathway to address the question,
      "Should the potential for gender differences be taken into account in the
      activity of exposure assessment for epidemiologic studies?" METHODS: Evidence
      from previously published studies and data from the investigators' own research
      were examined to explore whether or not several theoretical sources of gender
      'bias' in exposure assessment have been found in actual studies. Sources of bias
      examined included: differences in job tasks despite same job titles; differences
      in delivered exposure due to differences in protective equipment, body size, or
      other relationships to exposure sources; and differences in estimated exposure
      arising from study methods or design. RESULTS AND CONCLUSIONS: Evidence was found
      for gender differences (and thus potential bias) from all these sources, at least
      in some studies. We conclude that the answer to the question posed, "Does gender
      matter, in exposure assessment for epidemiology?" is a qualified 'yes,' but that
      the magnitude and direction of the potential bias cannot be predicted, a priori.
      Am. J. Ind. Med. 44:576-583, 2003.

PMID- 14635235
TI  - Pesticide exposure and women's health.
AB  - BACKGROUND: Research on pesticide-related health effects has been mostly focused
      in industrialized countries and in men. This paper discusses critical issues
      related to women's pesticide exposure and its effects on women's health. METHODS:
      The literature on pesticides was reviewed with emphasis on data related to women.
      Attention was focused on research suggesting different conditions of exposure or
      different response to pesticides by sex. Studies on cancer and reproductive
      effects were used as illustrative examples. RESULTS: Women are increasingly
      exposed to pesticides in developing countries, where women's poisoning and other
      pesticide-related injuries seem to be greatly underestimated. Many of the effects
      of pesticides in human health will be the same for men and women, but not always.
      Some organochlorine pesticides have been related to breast cancer in post
      menopausal women. However, knowledge about other pesticides is much more limited.
      Epidemiological studies assessing maternal exposure to individual pesticides and
      abortion, fetal death, or congenital defects are not conclusive, although some
      suggestive associations have been observed. CONCLUSIONS: Gender-sensitive
      research is needed to properly address the study of women's pesticide exposures
      and related adverse outcomes. A better understanding of potential gender
      environment and sex-environment interactions related to pesticide exposure and
      health effects in women is needed.

PMID- 14635236
TI  - Cancer among women textile workers in Shanghai, China: overall incidence
      patterns, 1989-1998.
AB  - BACKGROUND: Cancer incidence in women textile workers has not been adequately
      studied. The aim of this study was to examine site-specific cancer incidence
      patterns in a cohort of 267,400 women textile workers in Shanghai, China.
      METHODS: Women employed by the Shanghai Textile Industry Bureau (STIB) were
      followed for cancer incidence from 1989 to 1998. Age-adjusted standardized
      incidence ratios (SIRs) and 95% confidence intervals (CI) were computed based on
      Shanghai Cancer Registry (SCR) rates. RESULTS: There was a decrease in cancer
      incidence for the cohort compared with urban Shanghai women (SIR = 0.91, 95% CI =
      0.89-0.93). There were small increased risks of other endocrine tumors (SIR =
      1.31, 95% CI = 1.02-1.65). There were decreased risks for esophageal (SIR = 0.54,
      95% CI = 0.44-0.66), stomach (SIR = 0.79, 95% CI = 0.73-0.85), rectal (SIR =
      0.88, 95% CI = 0.78-0.98), lung (SIR = 0.80, 95% CI = 0.74-0.86), cervical (SIR =
      0.37, 95% CI = 0.28-0.50), ovarian (SIR = 0.85, 95% CI = 0.75-0.96), and bladder
      cancers (SIR = 0.63, 95% CI = 0.46-0.85). CONCLUSIONS: Women employed in the
      textile industry had a lower than expected cancer experience compared with urban
      Shanghai women. Further research on this cohort will examine associations between
      site-specific cancers and occupational exposures to dusts and chemicals.

PMID- 14635237
TI  - Cancer incidence among laboratory workers in biomedical research and routine
      laboratories in Israel: Part I-the cohort study.
AB  - BACKGROUND: Laboratory work is associated with exposure to a mixture of
      carcinogens. METHODS: The cohort is comprised of 4,300 laboratory workers. Cancer
      incidence was followed from 1960 to 1997. RESULTS: A total of 230 cases were
      included in the cohort. The overall cancer standardized incidence ratio (SIR) was
      1.04 (0.91-1.18). When a 20-year latency was introduced, SIR was increased
      significantly: 1.35 (1.13-1.61). Among routine workers and researchers, SIR was
      elevated significantly for the total population and for women, when a 20-year
      latency was introduced. SIR was also elevated significantly in research, routine,
      bacteriology and virology, and isotope laboratories. With respect to specific
      sites, significantly increased SIR was observed in breast, ovary, and thyroid
      cancer among women; and prostate cancer, leukemia, and melanoma among men.
      CONCLUSIONS: We suggest that work in research and biomedical laboratories might
      involve an increased risk of certain types of cancer. Am. J. Ind. Med. 44:600
      610, 2003.

PMID- 14635238
TI  - Cancer incidence among laboratory workers in biomedical research and routine
      laboratories in Israel: Part II-nested case-control study.
AB  - BACKGROUND: A case-control study nested within a cohort study of biomedical
      laboratory workers was conducted to examine whether the excess cancer morbidity
      that we found can be explained by exposure to a particular group of substances,
      taking into consideration potential confounders. METHODS: The study population
      included 163 cases and two matched control groups: laboratory workers (311) and
      general population (448) workers. RESULTS: Multiple conditional regression
      analysis showed that working in research laboratories involved an increased risk
      of cancer generally among women [risk ratio 2.2 (1.2-4.3)], and of breast cancer
      particularly [risk ratio 2.3 (1.1-4.7). Seventy-six percent (76%) of breast, 87%
      of thyroid, 60% of ovary and prostate, 94% of melanoma, and 50% of leukemia cases
      were ever exposed to at least one known human carcinogen. CONCLUSION: Our results
      exclude the possibility that the excess cancer morbidity was related to personal
      risk factors but they may be explained by exposure factors. Am. J. Ind. Med.
      44:611-626, 2003.

PMID- 14635239
TI  - Non-Hodgkin's lymphoma, leukemia, and exposures in agriculture: results from the
      Italian multicenter case-control study.
AB  - BACKGROUND: The etiology of non-Hodgkin's lymphoma (NHL) and leukemia is still
      largely unknown, but exposure to chemicals, in particular pesticides, has been
      suggested to be a risk factor. METHODS: A large population-based case-control
      study was conducted in Italy with the aim of investigating the associations
      between pesticide exposure and NHL, and solvents and leukemia. Data presented in
      this article refer to 1,575 interviewed cases and 1,232 controls in the nine
      agricultural study areas. RESULTS: Exposure to nitro-derivatives and phenylimides
      among fungicides, hydrocarbon derivatives and insecticide oils among
      insecticides, and the herbicide amides are the chemical classes observed to be
      associated with the pathologies under investigation. CONCLUSIONS: The results of
      the case-control study suggest an increased risk for NHL and leukemia, and some
      chemical classes of pesticides, although few are statistically significant and
      some are based on few exposed cases. The results also show that men and women
      experience both similar and different risks for the same environmental
      agricultural exposures. Am. J. Ind. Med. 44:627-636, 2003.

PMID- 14635240
TI  - Proportionate cancer mortality among workers in the Belarussian tanning industry.
AB  - BACKGROUND: The tanning industry involves many occupational exposures. This study
      evaluates proportionate cancer mortality among workers employed in the
      Belarussian tanning plant in Minsk. METHODS: A total of 768 workers with
      seniority of not less than 6 months who were hired after January 1, 1953 and died
      before December 31, 2000 was investigated. Proportionate mortality ratios (PMRs)
      were calculated using the population of Minsk to generate expected numbers.
      RESULTS: Among women employed in the tannery, there was a significant excess of
      pancreatic cancer, based on eight deaths (expected = 2.56, PMR = 3.13, 95% CI =
      1.35-6.17). Six of the eight pancreatic cancer deaths occurred among women
      occupied in dyeing-stuffing workshops (expected = 1.64, PMR = 3.67, 95% CI = 1.34
      7.97), all among workers hired between 1962 and 1984 (expected = 1.06, PMR =
      6.54, 95% CI = 2.6-13.4). CONCLUSIONS: Women in this tanning industry cohort
      experienced excess mortality of cancer of the pancreas, with suggested increases
      of corpus and cervix uteri, melanoma, and kidney cancers. For men, an
      insignificant increase in PMR of oral cavity-pharynx and pancreatic cancers was
      seen. Further prospective follow-up of living members of this cohort, will allow
      more in-depth analysis of rare cancer sites, latency, and duration of employment,
      and is warranted.

PMID- 14635241
TI  - Occupational exposures to extremely low frequency magnetic fields and
      postmenopausal breast cancer.
AB  - BACKGROUND: The association between occupational exposure to extremely low
      frequency magnetic fields (ELF-MF) and risk of postmenopausal breast cancer was
      assessed in a case-control study. METHODS: Breast cancer cases were compared to
      cancer controls. Interviewers elicited information on risk factors and on
      lifetime work history. Industrial hygienists assigned to each job average
      duration of exposure to ELF-MF at four levels of intensities ("none," <0.2
      microT; "low," 0.2-<0.5microT; "medium," 0.5-<1microT; "high," > or =1-10microT).
      Unconditional logistic regression was used to estimate adjusted odds ratios (OR)
      and 95% confidence intervals (95% CI). RESULTS: A total number of 608 cases and
      667 controls participated. Adjusting for accepted breast cancer risk factors, we
      found an OR of 1.13 for lifetime occupational exposure to ELF-MF at medium or
      high intensities. Risks were larger for exposures before age 35 (OR = 1.40), and
      statistically significant for exposures before 35 among cases with progesterone
      receptor positive tumors (OR = 1.56, 95% CI=1.02-2.39). CONCLUSIONS: There
      appears to be a small increased risk for breast cancer among postmenopausal women
      exposed occupationally to ELF-MF.

PMID- 14635242
TI  - Mortality and cancer morbidity experience of female workers at the British
      Nuclear Fuels Sellafield plant, 1946-1998.
AB  - BACKGROUND: Studies of nuclear workers have focused mainly on the experience of
      male workers. To date, little has been published specifically on the experience
      of female workers in the nuclear industry. METHODS: We report on the mortality,
      cancer morbidity, and tracing experience of the 6,376 females ever employed at
      the British Nuclear Fuels Ltd. plant at Sellafield to the end of 1998. These
      workers have accumulated 142,337 person-years of experience. RESULTS: Radiation
      workers were exposed to low doses of radiation. No statistically significant
      associations were noted between mortality or cancer morbidity and cumulative
      assessed organ-specific internal plutonium dose or cumulative external whole body
      radiation dose overall, or for any of the individual disease groupings examined.
      The power of the study was insufficient to detect the risks indicated in other
      radiation studies. CONCLUSION: This study offers reassurance that there is no
      detrimental effect on the health of the female workers from occupational
      exposures at Sellafield. Am. J. Ind. Med. 44:653-663, 2003.

PMID- 14635243
TI  - Falls in workers during pregnancy: risk factors, job hazards, and high risk
      occupations.
AB  - BACKGROUND: Although falls are a major source of trauma during pregnancy and 70%
      of pregnant women are employed, information on falls among pregnant workers is
      lacking. Study objectives were to estimate fall prevalence and risk factors among
      pregnant workers. METHODS: This retrospective cohort study used birth
      certificates to identify recently pregnant women. Data were collected via phone,
      internet, and mail surveys. The primary outcome investigated was a fall at work
      during pregnancy. Adjusted odds ratios (aOR) and confidence intervals (CI) were
      calculated. RESULTS: Of the 2,847 employed women, 26.6% (757) fell during their
      pregnancy and 6.3% (179) fell at work. Walking on slippery floors, hurrying, or
      carrying an object occurred in 66.3% of work falls. CONCLUSION: The service and
      teaching industry should be evaluated for risk reduction. Future research should
      determine if counseling during pregnancy will reduce falls in the workplace.

PMID- 14635244
TI  - The incidence of respiratory symptoms in female Swedish hairdressers.
AB  - BACKGROUND: Airway diseases in hairdressers are a concern. The objective of this
      investigation is to evaluate the risk for three respiratory symptoms, wheeze, dry
      cough, and nasal blockage, in hairdressers. METHODS: A questionnaire on
      respiratory symptoms, atopy, smoking, and work history was answered by 3,957
      female hairdressers and 4,905 women from the general population as referents.
      Incidence rates (IR) and incidence rate ratios (IRRs) for the three symptoms were
      estimated. RESULTS: The IRs of all three studied symptoms were higher in the
      hairdressers compared with the referents. Smoking modified the effects of cohort
      affiliation for all three symptoms; the combined effect from hairdressing work
      and smoking was less than expected. In addition, the effect of cohort affiliation
      for wheeze was also modified by atopy, and the effect of cohort affiliation for
      nasal blockage was also modified by calendar year. CONCLUSIONS: Hairdressing work
      was associated with increased incidences of respiratory symptoms. Smoking had a
      negative modifying effect.

PMID- 14635245
TI  - Psychosocial risk factors for musculoskeletal symptoms among women working in
      geriatric care.
AB  - BACKGROUND: Nursing is a stressful, physically demanding occupation and a rush
      setting for musculoskeletal problems. The aim of this study is to explore the
      extent of the association between psychosocial work characteristics and
      musculoskeletal symptoms among women working in geriatric care. METHODS: The
      participants were female employees of all geriatric nursing homes and geriatric
      hospital wards in Iceland having a staff of 10 or more. A total of 1,886
      questionnaires were distributed. The response rate was 80%. RESULTS: Finding the
      job mentally difficult, mental exhaustion after one's shift, dissatisfaction with
      supervisors or the flow of information, insufficient influence at work,
      dissatisfaction with the hierarchy, intense time pressure, lack of solidarity,
      dissatisfaction with the job, harassment, violence or threats at work; all of the
      aforementioned gave crude odds ratios (OR) two or above for one or more
      musculoskeletal symptoms. Mental exhaustion and harassment, violence, and threats
      were the factors connected with symptoms from all the body regions studied.
      CONCLUSIONS: The extent of the association of work-related psychosocial factors
      and musculoskeletal symptoms among the geriatric female nursing staff is
      substantial and needs to be taken into account by occupational health services
      and others involved in preventive work. Am. J. Ind. Med. 44:679-684, 2003.

PMID- 14635246
TI  - Depressive and anxiety symptoms among housemaids.
AB  - BACKGROUND: Housemaid, the most common occupation in the female labor force in
      Brazil, is known to be targeted by a generalized racial and job discrimination,
      which can generate mental suffering such as depressive and anxiety symptoms. In
      this cross-sectional study, the association between being a maid and having
      depressive and anxiety symptoms was evaluated. METHODS: Data for this study was
      taken from a former survey carried out in a random sample of 470 families living
      in a poor area of the city of Salvador, capital of the state of Bahia, Northeast
      Brazil. The study population comprised all women between the ages of 14 and 69,
      who reported having a paid occupation (n = 335). Data was collected by trained
      interviewers, using questionnaires. Psychological symptoms were identified using
      the Questionnaire for Psychiatric Morbidity among Adults, (QMPA), from which only
      those related to depression and anxiety (QMPA-SAD) were analyzed. RESULTS:
      Logistic regression showed that being a housemaid was positively associated with
      "sadness/tiredness" (adjusted prevalence ratio, PR(adj) = 1.64; 95% confidence
      interval, CI: 1.17-2.28), "poor concentration" (PR(adj) = 1.81; 95% CI: 1.13
      2.90), "palpitations" (PR(adj) = 2.22; 95% CI: 1.28-3.84), and "aggressive
      behavior" (PR(aj) = 1.58; 95% CI: 1.01-2.46). CONCLUSIONS: Although cross
      sectional designs are limited by causal inference, these results are in
      accordance with those obtained in qualitative studies. Advances in the Brazilian
      labor legislation with respect to domestic service may help to reduce social
      discrimination and contribute towards minimizing a possible mental burden
      resulting from this occupation.

PMID- 14635248
TI  - The spliceosome: the most complex macromolecular machine in the cell?
AB  - The primary transcripts, pre-mRNAs, of almost all protein-coding genes in higher
      eukaryotes contain multiple non-coding intervening sequences, introns, which must
      be precisely removed to yield translatable mRNAs. The process of intron excision,
      splicing, takes place in a massive ribonucleoprotein complex known as the
      spliceosome. Extensive studies, both genetic and biochemical, in a variety of
      systems have revealed that essential components of the spliceosome include five
      small RNAs-U1, U2, U4, U5 and U6, each of which functions as a RNA, protein
      complex called an snRNP (small nuclear ribonucleoprotein). In addition to snRNPs,
      splicing requires many non-snRNP protein factors, the exact nature and number of
      which has been unclear. Technical advances, including new affinity purification
      methods and improved mass spectrometry techniques, coupled with the completion of
      many genome sequences, have now permitted a number of proteomic analyses of
      purified spliceosomes. These studies, recently reviewed by Jurica and Moore,1
      reveal that the spliceosome is composed of as many as 300 distinct proteins and
      five RNAs, making it among the most complex macromolecular machines known.

PMID- 14635249
TI  - Investigating protein-protein interfaces in bacterial transcription complexes: a
      fragmentation approach.
AB  - Transcription initiation by sigma(54)-RNA polymerase (RNAP) relies explicitly on
      a transient interaction with a complex molecular machine belonging to the AAA+
      (ATPases associated with various cellular activities) superfamily. Members of the
      AAA+ superfamily convert chemical energy derived from NTP hydrolysis to a
      mechanical force used to remodel their target substrate. Recently Bordes and
      colleagues,1 using a protein fragmentation approach, identified a unique sequence
      within sigma(54)-dependent transcriptional activators that constitutes a
      sigma(54)-binding interface. This interface is not static, but subject to
      nucleotide-dependent movement which may represent a common mechanism for
      controlling output that has been adopted by other AAA+ proteins.

PMID- 14635250
TI  - Move it on over: getting proteins across biological membranes.
AB  - The translocation of proteins across membranes is a central problem in biology.
      Regardless of the system in question, delivering proteins across a given membrane
      relies on many of the same basic themes. At the same time, however, each membrane
      translocation system, be it signal-gated or signal-assembled, makes use of
      components unique to that system. The latest findings on protein translocation
      across a variety of biological membranes have been presented in a recent review
      article.

PMID- 14635251
TI  - Perpetuating the double helix: molecular machines at eukaryotic DNA replication
      origins.
AB  - The hardest part of replicating a genome is the beginning. The first step of DNA
      replication (called "initiation") mobilizes a large number of specialized
      proteins ("initiators") that recognize specific sequences or structural motifs in
      the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the
      enzymatic activities required for DNA synthesis, such as helicases, primases and
      polymerases. All of these components are orderly assembled before the first
      nucleotide can be incorporated. On the occasion of the 50th anniversary of the
      discovery of the DNA structure, we review our current knowledge of the molecular
      mechanisms that control initiation of DNA replication in eukaryotic cells, with
      particular emphasis on the recent identification of novel initiator proteins. We
      speculate how these initiators assemble molecular machines capable of performing
      specific biochemical tasks, such as loading a ring-shaped helicase onto the DNA
      double helix.

PMID- 14635252
TI  - Macromolecular complexes that unwind nucleic acids.
AB  - In this essay, we consider helicases, defined as enzymes that use the free
      energies of binding and hydrolysis of ATP to drive the unwinding of double
      stranded nucleic acids, and ask how they function within, and are "coupled" to,
      the macromolecular machines of gene expression. To illustrate the principles of
      the integration of helicases into such machines, we consider the macromolecular
      complexes that direct and control DNA replication and DNA-dependent RNA
      transcription, and use these systems to illustrate how machines centered around
      coupled polymerase-helicase systems can be regulated by small changes in the
      interactions of their functional components.

PMID- 14635253
TI  - Building and breaking bridges between sister chromatids.
AB  - Eukaryotic chromosomes undergo dramatic changes and movements during mitosis.
      These include the individualization and compaction of the two copies of
      replicated chromosomes (the sister chromatids) and their subsequent segregation
      to the daughter cells. Two multisubunit protein complexes termed 'cohesin' and
      'condensin', both composed of SMC (Structural Maintenance of Chromosomes) and
      kleisin subunits, have emerged as crucial players in these processes. Cohesin is
      required for holding sister chromatids together whereas condensin, together with
      topoisomerase II, has an important role in organizing individual axes of sister
      chromatids prior to their segregation during anaphase. SMC and kleisin complexes
      also regulate the compaction and segregation of bacterial nucleoids. New research
      suggests that these ancient regulators of chromosome structure might function as
      topological devices that trap chromosomal DNA between 50 nm long coiled coils.

PMID- 14635254
TI  - Chromatin remodeling by ATP-dependent molecular machines.
AB  - The eukaryotic genome is packaged into a periodic nucleoprotein structure termed
      chromatin. The repeating unit of chromatin, the nucleosome, consists of DNA that
      is wound nearly two times around an octamer of histone proteins. To facilitate
      DNA-directed processes in chromatin, it is often necessary to rearrange or to
      mobilize the nucleosomes. This remodeling of the nucleosomes is achieved by the
      action of chromatin-remodeling complexes, which are a family of ATP-dependent
      molecular machines. Chromatin-remodeling factors share a related ATPase subunit
      and participate in transcriptional regulation, DNA repair, homologous
      recombination and chromatin assembly. In this review, we provide an overview of
      chromatin-remodeling enzymes and discuss two possible mechanisms by which these
      factors might act to reorganize nucleosome structure.

PMID- 14635255
TI  - Starting the protein synthesis machine: eukaryotic translation initiation.
AB  - The final assembly of the protein synthesis machinery occurs during translation
      initiation. This delicate process involves both ends of eukaryotic messenger RNAs
      as well as multiple sequential protein-RNA and protein-protein interactions. As
      is expected from its critical position in the gene expression pathway between the
      transcriptome and the proteome, translation initiation is a selective and highly
      regulated process. This synopsis summarises the current status of the field and
      identifies intriguing open questions.

PMID- 14635256
TI  - Kinesin motors as molecular machines.
AB  - Molecular motor proteins, fueled by energy from ATP hydrolysis, move along actin
      filaments or microtubules, performing work in the cell. The kinesin microtubule
      motors transport vesicles or organelles, assemble bipolar spindles or
      depolymerize microtubules, functioning in basic cellular processes. The mechanism
      by which motor proteins convert energy from ATP hydrolysis into work is likely to
      differ in basic ways from man-made machines. Several mechanical elements of the
      kinesin motors have now been tentatively identified, permitting researchers to
      begin to decipher the mechanism of motor function. The force-producing
      conformational changes of the motor and the means by which they are amplified are
      probably different for the plus- and minus-end kinesin motors.

PMID- 14635257
TI  - The blood coagulation system as a molecular machine.
AB  - The human blood coagulation system comprises a series of linked glycoproteins
      that upon activation induce the generation of downstream enzymes ultimately
      forming fibrin. This process is primarily important to arrest bleeding
      (hemostasis). Hemostasis is a typical example of a molecular machine, where the
      assembly of substrates, enzymes, protein cofactors and calcium ions on a
      phospholipid surface markedly accelerates the rate of coagulation. Excess,
      pathological, coagulation activity occurs in "thrombosis", the formation of an
      intravascular clot, which in the most dramatic form precipitates in the
      microvasculature as disseminated intravascular coagulation. Thrombosis occurs
      according to a biochemical machine model in the case of atherothrombosis on a
      ruptured atherosclerotic plaque, but may develop at a slower rate in venous
      thrombosis, illustrating that the coagulation machinery can act at different
      velocities. The separate coagulation enzymes are also important in other
      biological processes, including inflammation for which the rapid conversion of
      one coagulation factor by the other is not a prerequisite. The latter role of
      coagulation enzymes may be related to the old and probably maintained function of
      the coagulation machine in innate immunity.

PMID- 14635259
TI  - Interview with Matthew Meselson.

PMID- 14635258
TI  - Synapse signalling complexes and networks: machines underlying cognition.
AB  - All thoughts and actions are encoded in patterns of neuronal electrical activity.
      Circuits of nerve cells connected by synapses are dedicated to processing
      information in these patterns. Information is not only transmitted across the
      synapse but also monitored by postsynaptic molecular machines. These machines are
      macromolecular complexes of approximately 100 proteins organised into a network
      of protein interactions. The network can be mathematically described as a scale
      free network. Components of the complexes are necessary for decoding the neural
      code and converting electrical information into biochemical changes. The network
      properties of these complexes may explain many of the features of neuronal
      plasticity and cognitive function in rodents. Importantly, these multiprotein
      complexes and their network properties shed new light on the basis of human
      cognitive diseases including schizophrenia, autism, Huntington's disease and
      mental retardation. Supplementary material for this article can be found on the
      BioEssays website http://www.interscience.wiley.com/jpages/0265
      9247/suppmat/index.html.

PMID- 14635260
TI  - Moving from model to non-model organisms? Lessons from Nasonia wasps.

PMID- 14635261
TI  - Levels of polymorphism on the sex-limited chromosome: a clue to Y from W?

PMID- 14635262
TI  - Genistein treatment protects mice from ionizing radiation injury.
AB  - The radioprotective and behavioral effects of an acute administration of the
      isoflavone genistein (4',5,7-trihydroxyflavone) were investigated in adult CD2F1
      male mice. Mice were administered a single subcutaneous (s.c.) dose of genistein
      either 24 h or 1 h before a lethal dose of gamma radiation (9.5-Gy of cobalt-60
      at 0.6 Gy min(-1)). Mice received saline, PEG-400 vehicle or genistein at 3.125,
      6.25, 12.5, 25, 50, 100, 200, or 400 mg kg(-1) body weight. For mice treated 24 h
      before irradiation there was a significant increase in 30-day survival for
      animals receiving genistein doses of 25 to 400 mg kg(-1) (p<0.001). In contrast,
      the 30-day survival rates of mice treated with genistein 1 h before irradiation
      were not significantly different from those of the vehicle control group.
      Additionally, the acute toxicity of genistein was evaluated in non-irradiated
      male mice administered a single s.c. injection of saline, vehicle, or genistein
      at 100, 200 or 400 mg kg(-1). At these genistein doses there were no adverse
      effects, compared with controls, on locomotor activity, grip strength, motor
      coordination, body weight, testes weight, or histopathology. These results
      demonstrate that a single s.c. administration of the flavonoid genistein at non
      toxic doses provides protection against acute radiation injury.

PMID- 14635263
TI  - Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice
      and rats.
AB  - This evaluation was part of a much more comprehensive testing program to
      characterize the mammalian toxicity potential of the gasoline oxygenator additive
      tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency
      mandate. A developmental toxicity hazard identification study was conducted by
      TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant
      CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors
      containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice)
      or 6-19 (rats). The developmental toxicity hazard potential was evaluated
      following the study design draft guidelines and end points proposed by the United
      States Environmental Protection Agency. Based on maternal body weight changes
      during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for
      maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using
      the criterion of near-term fetal body weights. In mice, more profound
      developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At
      the highest concentration, mouse litters revealed more late fetal deaths,
      significantly reduced fetal body weights per litter and increased incidences of
      cleft palate (classified as an external malformation), as well as enlarged
      lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse
      fetuses also exhibited an increased incidence of cleft palate and the dam body
      weights were reduced. Therefore, the NOAEL for the mouse maternal and
      developmental toxicity was 250 ppm under the conditions of this study.

PMID- 14635264
TI  - Two-generation reproductive toxicity study of inhaled tertiary amyl methyl ether
      (TAME) vapor in CD rats.
AB  - Under Office of Prevention, Pesticides and Toxic Substances draft guidelines, CD
      weanling F0 rats (30 of each gender per group) inhaled tertiary amyl methyl ether
      vapor at 0, 250, 1500 or 3000 ppm 5 days a week and 6 h a day for 10 weeks, with
      vaginal cytology evaluated for weeks 8-10. The F0 animals then produced F1
      offspring, with exposure 7 days a week from mating through to lactation. During
      the F1 prebreed exposure period, vaginal patency, preputial separation (PPS) and
      vaginal cytology were evaluated. The F1 animals were mated, with F2 anogenital
      distance measured on postnatal day zero. At F2 weaning 30 of each gender per
      group were selected for postwean retention, with no exposures, through vaginal
      patency and PPS. Body weights, feed consumption and clinical signs were recorded
      throughout the study. Adult F0 and F1 systemic toxicity was present at 1500 and
      3000 ppm. Minor adult male reproductive toxicity was present at 3000 ppm. There
      were no adult effects on vaginal cyclicity, estrous cycle length, mating,
      fertility, pregnancy, gestational length or ovarian and uterine weights. There
      were no treatment-related gross or histopathologic findings in parental male or
      female systemic or reproductive organs. The F1 and F2 offspring toxicity was
      present at 1500 and 3000 ppm. The no-observable-adverse-effect level for adult
      systemic and offspring toxicity was 250 ppm and 1500 ppm for male reproductive
      toxicity (females at >3000 ppm).

PMID- 14635265
TI  - Characterization of metabolites and disposition of tertiary amyl methyl ether in
      male F344 rats following inhalation exposure.
AB  - Tertiary amyl methyl ether (TAME) is a fuel additive used to reduce carbon
      monoxide in automobile emissions. Because of the potential for human exposure,
      this study was conducted to develop methods for the characterization and
      quantitation of metabolites in expired air and excreta of rats exposed to a
      mixture of [13C]- and [14C]TAME ([2,3,4-13C]- and [2-14C]2-methoxy-2
      methylbutane). The distribution of TAME in rats was determined following
      inhalation exposure, and TAME-derived metabolites were characterized in expired
      air and urine. Male rats were exposed for 6 h via nose-only inhalation to 2500
      ppm [14C/13C]TAME, and expired air, urine and feces were collected for up to 7
      days. Over 95% of the total recovered radioactivity was excreted by 48 h after
      exposure. Recovered radioactivity was expired as organic volatiles (44%) and
      14CO2 (3%) and excreted in urine (51%) and feces (1%). Both TAME and its
      metabolite tertiary amyl alcohol (TAA) accounted for > or =90% of the radiolabel
      in expired air 0-8 h following exposure termination. Three major urinary
      metabolites of TAME were identified: (1) a direct glucuronide conjugate of TAA;
      (2) a product of oxidation at the methylene carbon of TAA (2,3-dihydroxy-2
      methylbutane); (3) a glucuronide conjugate of metabolite 2. Metabolite 1
      accounted for most of the TAME-derived metabolites excreted 0-8 h following
      exposure termination. Further metabolic products of TAA (metabolites 2 and 3)
      accounted for most of the excreted TAME-derived metabolites at later time points.

PMID- 14635266
TI  - Blood pharmacokinetics of tertiary amyl methyl ether in male and female F344 rats
      and CD-1 mice after nose-only inhalation exposure.
AB  - Interest in understanding the biological behavior of aliphatic ethers has
      increased owing to their use as gasoline additives. The purpose of this study was
      to investigate the blood pharmacokinetics of the oxygenate tertiary amyl methyl
      ether (TAME), its major metabolite tertiary amyl alcohol (TAA) and acetone in
      rats and mice following inhalation exposure to TAME. Species differences in the
      area under the curve (AUC) for TAME were significant at each exposure
      concentration. For rats, the blood TAME AUC increased in proportion with an
      increase in exposure concentration. For mice, an increase in exposure
      concentration (100-500 ppm) resulted in a disproportional increase in the TAME
      AUC. Mice had greater (two- to threefold) blood concentrations of TAA compared
      with rats following exposure to 2500 or 500 ppm TAME. Mice had a disproportional
      increase in the TAA AUC with an increase in exposure concentration (100-500 ppm).
      This difference could result from saturation of a process (e.g. oxidation,
      glucuronide conjugation) that is involved in the further metabolism of TAA. For
      each species, gender and exposure concentration, acetone increased during
      exposure and returned to control values by 16 h following exposure. The source of
      acetone could be both as a metabolite of TAA or an effect on endogenous
      metabolism produced by exposure to TAME.

PMID- 14635267
TI  - Species and gender differences in the metabolism and distribution of tertiary
      amyl methyl ether in male and female rats and mice after inhalation exposure or
      gavage administration.
AB  - Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce
      emissions. Understanding the metabolism and distribution of TAME is needed to
      assess potential human health issues. The effect of dose level, duration of
      exposure and route of administration on the metabolism and distribution of TAME
      were investigated in male and female F344 rats and CD-1 mice following inhalation
      or gavage administration. By 48 h after exposure, >96% of the administered
      radioactivity was expired in air (16-71%) or eliminated in urine and feces (28
      72%). Following inhalation exposure, mice had a two- to threefold greater
      relative uptake of [14C]TAME compared with rats. Metabolites were excreted in
      urine of rats and mice that are formed by glucuronide conjugation of tertiary
      amyl alcohol (TAA), oxidation of TAA to 2,3-dihydroxy-2-methylbutane and
      glucuronide conjugation of 2,3-dihydroxy-2-methylbutane. A saturation in the
      uptake and metabolism of TAME with increased exposure concentration was indicated
      by a decreased relative uptake of total [14C]TAME equivalents and an increase in
      the percentage expired as volatiles. A saturation of P-450 oxidation of TAA was
      indicated by a disproportional decrease of 2,3-dihydroxy-2-methylbutane and its
      glucuronide conjugate with increased exposure concentration.

PMID- 14635268
TI  - Histopathological and biochemical changes in lung tissues of rats following
      administration of fluoride over several generations.
AB  - The possible effects of multigenerational administration of sodium fluoride (NaF)
      via drinking water on lung tissue morphology and biochemistry and body and lung
      weight were investigated in second-generation adult male rats. For this purpose
      we selected 45 Albino adult Wistar rats in nine cages, each of which consisted of
      four females and one male. Twenty-eight pregnant rats were selected for the
      experiment, divided into four groups of seven rats given 1 (control group), 10,
      50 and 100 mg l(-1) NaF in drinking water during the gestation period. After
      gestation the rats had 165 pups in total. The mothers received fluoridated water
      during the lactation period and the offspring of the first generation had access
      to fluoridated water during the suckling period (21 days) and after the weaning
      period (30 days) until they became mature and at the start of the second part of
      the experiment. During this time 23 pups died and 79 female and 63 male first
      generation rats survived. These first-generation rats were then used to obtain
      the second-generation offspring in the same manner as before, which were
      subjected to the same treatments. At the end of 6 months the rats were sacrificed
      and autopsied. Serum fluoride levels and the activities of principal antioxidant
      enzymes were determined in lung tissue samples taken from all groups. In
      addition, the lung tissues were submitted for histopathological examination.
      Histological findings showed alveolar congestion, alveolar cell hyperplasia and
      necrosis, prominent alveolar septal vessels, epithelial desquamation and
      macrophages in the alveolar spaces in the experimental groups. Additionally,
      there were inflammatory infiltrations in peribronchial, perivascular,
      intraparenchymal and respiratory tract lumen; intraparenchymal hyperaemic
      vessels; respiratory epithelial desquamation and proliferation; intraparenchymal
      thick walled vessels; parenchymal fibrosis; bronchiolitis; pneumonic and focal
      emphysematous areas. Furthermore, the lung parenchyma was observed to have a
      distorted appearance with loss of alveolar architecture. These histopathological
      findings were more pronounced for the rat groups of 50 and 100 mg l(-1) fluoride.
      No significant histopathological changes were observed in the rats of the control
      group. The increased activities of superoxide dismutase (SOD) and reduced
      glutathione peroxidase (GSH-Px) and the decreased activity of catalase (CAT) in
      the lung tissues with 10 mg l(-1) fluoride might indicate activation of the
      antioxidant defence mechanism. The decrease in SOD, GSH-Px and CAT activities
      with 50 and 100 mg l(-1) fluoride and the increase in thiobarbituric acid
      reactive substance levels might be related to oxidative damage that occurred in
      the lung. This multigenerational evaluation of the long-term effect of different
      doses of fluoride intake through drinking water on lung damage shows that the
      lung tissues were damaged, there was emphysema and inflammation of lung
      parenchyma associated with loss of alveolar architecture and the degree of lung
      damage seemed to correlate with the increased dosage of fluoride. A similar
      relationship was observed between the degree of lung damage, body and lung weight
      and serum fluoride levels according to the fluoride dose. Therefore, these
      results contribute to a better understanding of chronic fluoride toxicity in lung
      tissue of second-generation rats, especially via drinking water, and the
      biochemical findings were in agreement with histological observations. In
      addition, increased fluoride concentration did not affect reproduction or the
      number of pups dying but the body weight and lung weight ratios were affected by
      the high dose of fluoride in a dose-related pattern.

PMID- 14635269
TI  - In vitro protection of red blood cell acetylcholinesterase by metoclopramide from
      inhibition by organophosphates (paraoxon and mipafox).
AB  - Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor
      agonist widely used as an antiemetic and gastric prokinetic drug. In addition,
      MCP is a reversible inhibitor of cholinesterases from the human central nervous
      system and blood, and may have a red blood cell (RBC) acetylcholinesterase (AChE)
      protective effect against inhibition by organophosphates. The purpose of the
      study was to quantify 'in vitro', by means of the IC50 shift, the extent of MCP
      conferred protection, by using paraoxon (POX) and mipafox (MPFX) as inhibitors.
      Paraoxon is a widely used non-neuropathic organophospate responsible for a large
      number of accidental or suicidal exposures. Mipafox is a neuropathic
      organophospate. Red blood cell AChE activities in human plasma were measured
      photometrically in the presence of different POX, MPFX and MCP concentrations and
      the IC50 was calculated. Determinations were repeated in the presence of
      increasing MCP concentrations. It appears that the IC50 shift induced by the
      presence of MCP increases with the MCP concentration in a linear manner. The
      protective effect of MCP on cholinesterases could be of practical relevance in
      the treatment of POX and MPFX poisoning. We conclude that in vivo testing of MCP
      as an organophosphate protective agent is warranted.

PMID- 14635270
TI  - Effect of ribavirin, levovirin and viramidine on liver toxicological gene
      expression in rats.
AB  - The ribavirin/interferon-alpha combination is currently the standard therapy for
      patients with chronic hepatitis C. However, ribavirin causes hemolytic anemia as
      a significant side-effect. Levovirin, an L-enantiomer of ribavirin, possesses
      similar immunomodulatory activity to ribavirin but lacks direct antiviral
      activity or hemolytic anemia. Viramidine is a liver-targeting prodrug of
      ribavirin with much less potential for hemolytic anemia. The aim of the present
      study is to profile the hepatic toxicological gene response to ribavirin,
      levovirin and viramidine. Rats were dosed orally with 120 mg kg(-1) day(-1) of
      ribavirin and viramidine and 2000 mg kg(-1) day(-1) of levovirin for 8 days.
      Ribavirin did not cause any significant change (>threefold) in gene expression as
      analyzed by the Affymetrix GeneChip technique. Levovirin decreased the mRNA level
      of CYP7A1 by fourfold but did not affect the expression of CYP27/CYP7B1 that
      functions as an alternative pathway for cholesterol metabolism. Viramidine down
      regulated both expressed sequence tag 233569 and heat shock protein 86 genes
      threefold. The changes at mRNA level of these genes were confirmed by the reverse
      transcription competitive polymerase chain reaction technique. None of the
      compounds changed the liver/body weight ratio, the major cytochrome P-450 protein
      levels or enzyme activities. The data indicated that a high dose of ribavirin,
      levovirin or viramidine did not cause significant change at the transcription
      level of most of the liver toxicological genes.

PMID- 14635271
TI  - Glucosamine and chondroitin for osteoarthritis: to recommend or not to recommend?

PMID- 14635272
TI  - Ambulatory care or home-based treatment? An economic evaluation of two
      physiotherapy delivery options for people with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the difference in costs of home-based versus clinic-based
      physiotherapy (PT) for patients with rheumatoid arthritis (RA) from a societal
      perspective. METHODS: A cost analysis was performed using statistical and
      financial information provided by The Arthritis Society, Ontario Division, from
      April 1, 1997 to March 30, 1998. Cost estimates included treatment costs and
      costs borne by patients. A sensitivity analysis was conducted to examine the
      effect of altering the valuation of treatment time and patient employment status.
      RESULTS: Total costs per case were $210.87 for the home setting, and $183.87 for
      the clinic setting when patients were employed. Sensitivity analysis did not
      change the trend of the results. The estimated start-up costs for an arthritis
      clinic were between $302.90 and $652.40. From the perspective of the health care
      system, these costs would be recovered after serving 4 to 8 RA patients at a
      clinic. CONCLUSION: The findings suggest that ambulatory PT care is less costly
      than home-based services for people with RA based on The Arthritis Society model.
      Further studies should be conducted to examine the effectiveness and the possible
      adverse consequences of alternative settings for service delivery.

PMID- 14635273
TI  - A biomechanical analysis of a medial unloading brace for osteoarthritis in the
      knee.
AB  - OBJECTIVES: The goals of the study were to measure the force applied to the
      lateral side of the knee by a valgus loading brace designed for patients with
      medial compartment osteoarthritis (OA) and to compare the varus moment at the
      knee during level gait with and without the brace. METHODS: Five subjects
      diagnosed with medial compartment OA were fitted with a custom Monarch valgus
      loading knee brace. A 3-dimensional videobased motion analysis system and force
      plate information were used to calculate forces and moments at the knee. An
      instrumented condylar bladder was used to determine the force applied to the knee
      by the brace. The varus moments for the braced and unbraced trials were compared
      during gait at 15%, 20%, 25%, and 30% of stance. RESULTS: The Monarch brace
      significantly reduced the varus moment at 20% and 25% of stance. The valgus force
      measured with the custom condylar bladder remained fairly constant throughout the
      first 80% of the stance phase. CONCLUSIONS: The reduced various moment observed
      for the braced condition demonstrates the biomechanical function of the brace in
      5 subjects and may contribute to a reduction of pain for patients with medial
      compartment OA.

PMID- 14635274
TI  - Sustained improvement produced by nonpharmacologic intervention in fibromyalgia:
      results of a pilot study.
AB  - OBJECTIVE: The aim of this pilot study was to examine the practicality of
      delivering a package of nonpharmacologic, behavioral-based treatment, previously
      found to be effective in chronic back pain, to patients with fibromyalgia (FM)
      and to assess the efficacy of the intervention using a range of outcome measures
      up to 4 months posttreatment. METHODS: Participants with FM (n = 28) formed a
      single group for 8 sessions at weekly intervals. Each session comprised an
      education/cognitive-behavioral component, formal relaxation/meditation training,
      and instruction in a Chinese movement therapy (Qi Gong). RESULTS: Twenty of 28
      subjects completed at least 5 of the 8 sessions. Significant improvement was seen
      in the Fibromyalgia Impact Questionnaire and a range of other outcome measures
      including tender points and pain threshold. Improvement was sustained 4 months
      after the end of the intervention. CONCLUSION: A simple behavioral intervention
      using large groups can be administered to subjects with FM and appears to produce
      sustained benefit in a range of outcomes. Controlled trials are currently being
      planned.

PMID- 14635275
TI  - Development and initial evaluation of a culturally sensitive cholesterol-lowering
      diet program for Mexican and African American patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To develop and evaluate acceptability of an intensive and ethnic
      specific cholesterol-lowering diet program with a strong behavioral component in
      patients with systemic lupus erythematosus (SLE). METHOD: A comprehensive program
      with a behavioral component and culturally sensitive menus was developed in an
      effort to alter dietary behavior in patients with SLE. Four SLE patients, 2
      African American and 2 Mexican American, enrolled in this program. Data on food
      intake (3-day food record), acceptability of the program (subjective response),
      and physiologic variables were collected at baseline, 6 weeks, and 12 weeks.
      RESULTS: The program was highly rated by all patients and found to be
      informative, easy to understand, ethnically sensitive, and to contain useful
      behavioral maintenance strategies. All 4 patients surpassed or were close to
      their diet goals at both 6 and 12 weeks. In this small group of patients, there
      was a statistically significant reduction in low-density lipoprotein cholesterol
      (P = 0.04) and body weight (P = 0.001), as assessed by repeated measures analysis
      of variance. CONCLUSION: The culturally specific cholesterol-reducing diet
      program was highly rated and appeared to be effective in changing the diet of
      this small group of SLE patients, as determined by their food records and body
      weight. The impact of this program, including the individual components on
      cardiovascular disease risk factors, needs to be evaluated in a larger multiple
      arm study with a lengthier intervention.

PMID- 14635276
TI  - Medical resource use and costs among rheumatoid arthritis patients receiving
      disease-modifying antirheumatic drug therapy.
AB  - OBJECTIVE: To identify costs among rheumatoid arthritis (RA) patients receiving
      alternative disease-modifying antirheumatic drug (DMARD) therapies. METHODS:
      Using managed care organization data, we identified members who (a) were
      prescribed any DMARD therapy for two consecutive months between July 1993 and
      February 1998, (b) were aged > or = 18 years, (c) had > or = 6 months of DMARD
      free enrollment prior to the first DMARD, and (d) had a diagnosis of RA. RESULTS:
      The average age of the cohort (n = 571) was 51 years, and 70% were women. Mean
      duration of enrollment following initiation of DMARD therapy (observation period)
      was 19.5 months; 28.8% of patients switched DMARD regimens. The average monthly
      cost of care was $853, of which $294 (34%) was for RA-coded medical services.
      Monthly RA-coded costs varied by DMARD: hydroxychloroquine $227 (n = 252),
      methotrexate $340 (n = 185); sulfasalazine $233 (n = 49), and other
      mono/combination therapy $425 (n = 85) (P = 0.001). CONCLUSION: Costs of RA-coded
      care in patients receiving DMARDs are low and vary by DMARD.

PMID- 14635277
TI  - Development and preliminary validation of a self-efficacy measure for use among
      parents of children with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To develop a valid and reliable measure to assess parents' perceived
      ability to control, or manage, aspects of their children's juvenile idiopathic
      arthritis (JIA). METHODS: Construction of the Parent's Arthritis Self-Efficacy
      Scale (PASE) was based on existing knowledge and the results of focus groups with
      parents of children with JIA, children with JIA, and health professionals. Data
      for validation of the PASE were collected by self-administered questionnaires
      completed by 178 parents and 89 children with JIA. RESULTS: Analyses revealed a 2
      factor structure for both mothers and fathers. These factors related to parents'
      self-efficacy for managing children's arthritis-related symptoms and psychosocial
      health. Taken together, the two factors explained 75.5% and 65.8% of the total
      variance (mothers' and fathers,' respectively). The PASE demonstrated high
      internal consistency, concurrent validity, and construct validity, particularly
      among mothers. CONCLUSION: Preliminary findings suggest that the PASE is worthy
      of further psychometric testing and may have the potential to help delineate
      variations in adjustment among parents of children with JIA.

PMID- 14635278
TI  - Notes on the history of eponymic idiopathic vasculitis: the diseases of Henoch
      and Schonlein, Wegener, Churg and Strauss, Horton, Takayasu, Behcet, and
      Kawasaki.

PMID- 14635279
TI  - The diagnosis of crystal-induced arthritis: comment on the article by Segal and
      Albert.

PMID- 14635280
TI  - Reliability and validity of the Arthritis Hand Function Test in adults with
      systemic sclerosis (scleroderma).
AB  - OBJECTIVE: To determine the interrater and test-retest reliability and validity
      of the Arthritis Hand Function Test (AHFT) in persons with systemic sclerosis.
      METHODS: Interrater reliability of the AHFT was established by two raters
      independently scoring the performances of 20 women with systemic sclerosis. The
      same group of subjects was tested again 7-10 days later to determine test-retest
      reliability. Concurrent validity was established by the subjects' self-reports of
      their abilities to perform activities of daily living as measured by the Health
      Assessment Questionnaire and the Arthritis Impact Measurement Scales 2 (AIMS2).
      RESULTS: All of the items had excellent interrater intraclass correlation
      coefficients (ICC = 0.99-1.00). The ICCs for test-retest reliability were in the
      excellent (ICC = 0.80-0.97) range for most of the items and moderate (ICC = 0.57
      0.73) for the others. Most of the items were moderately correlated with items on
      the AIMS2 (r = 0.45-0.69). CONCLUSION: The results from this study suggest that
      the AHFT is a reliable and valid test to measure hand function in persons with
      systemic sclerosis.

PMID- 14635281
TI  - The disease process and utilization of health services in rheumatoid arthritis:
      the relative contributions of various markers of disease severity in explaining
      consumption patterns.
AB  - OBJECTIVE: To examine the predictive ability of a wide array of measures of
      disease severity in explaining Dutch and German patterns of health services
      utilization during a 2-year period. METHODS: Slightly over 200 rheumatoid
      arthritis (RA) patients, 136 from a Dutch and 98 from a German outpatient clinic,
      supplied information on symptom and functional status, global health, and
      emotional and social functioning at baseline. The patients' rheumatologists
      provided clinical assessments of functional grade and disease activity. A
      questionnaire mailed twice at 12-month intervals was the source of retrospective
      information on physician consultations, hospitalization, and referrals for
      surgery and physical therapy during the previous period. Major determinants of
      use were studied with multivariate analyses. RESULTS: German patients reported
      more frequent physician contacts than Dutch patients, but the volume of surgery,
      hospital admissions, and referrals for physical therapy did not differ between
      the two countries. In a hierarchical regression, the consultation rate was
      directly associated with pain quality and global health. Markers of RA
      progression were related to surgery, and the latter to volume of in-hospital
      care. Fatigue severity and physical disability predicted referrals for physical
      therapy. Patient self-management activities were only weakly associated with
      disease severity variables. CONCLUSION: The activity and damage components of RA
      were related to the separate components of total health service utilization.
      Disease activity was the prime determinant of physician services used, and RA
      progression the determinant of surgical interventions and hospitalization.

PMID- 14635282
TI  - Adaptations made by rheumatoid arthritis patients to continue working: a pilot
      study of workplace challenges and successful adaptations.
AB  - OBJECTIVES: The goals of this pilot study were to use qualitative research
      techniques in a group of currently employed patients with rheumatoid arthritis
      (RA) to develop categories of challenges encountered in maintaining employment
      and categories of successful adaptations made to continue working; and to
      identify obstacles considered to be persistent threats to continued employment.
      METHODS: Patients were interviewed by telephone with a questionnaire composed of
      structured-response format and open-ended response format questions focusing on
      specific challenges and adaptations in the workplace. RESULTS: Of the 22 patients
      interviewed, 96% were women, mean age was 50 years, 84% were college graduates,
      and the majority had light physical job demands and high autonomy over their work
      and hours worked. Patients encountered diverse challenges, such as fatigue, pain,
      typing, writing, physical requirements, maintaining a pleasant disposition,
      working overtime, traveling for business, commuting, being on time, not being
      able to choose rest periods, and environmental issues. Patients also made
      multiple adaptations to continue working, the most helpful being changing job or
      altering career path (36%), altering work hours (32%), using more disease
      modifying antirheumatic drugs (27%), using car service (23%), sleeping more
      (18%), and working at home (14%). Patients were not at all confident in their
      ability to continue working because of RA, and perceived the following persistent
      threats to continued employment: fatigue (45%), not being able to use hands
      (45%), not being able to choose rest periods (27%), and commuting problems (18%).
      In addition, patients confronted psychological stresses, such as dealing with
      coworkers and supervisors and balancing job and personal roles. These challenges
      and adaptations included unfavorable work-related occurrences, or "negative work
      role events." CONCLUSIONS: Seemingly successfully employed patients with RA faced
      multiple challenges and made major adaptations to maintain employment and still
      perceived their employment to be in jeopardy because of RA. The findings of this
      study have important implications for screening patients at risk for negative
      work-role events and for possible work-related and social support interventions
      aimed at preserving employment.

PMID- 14635283
TI  - Feasibility of an eight-week dance-based exercise program and its effects on
      locomotor ability of persons with functional class III rheumatoid arthritis.
AB  - OBJECTIVES: The main objectives of this experimental case series were to evaluate
      the feasibility of a modified dance-based exercise program with low ground
      impacts in persons with rheumatoid arthritis (RA) functional class III and to
      describe its effects on locomotor ability. The relationship between 3 locomotor
      tests and their responsiveness also were addressed. METHODS: Ten female subjects
      participated in an 8-week exercise program. Locomotor ability was measured before
      and after the program using the 50-foot test of walking time, the 6-minute test
      of walking distance, and the locomotion biomechanical analysis. RESULTS: All
      subjects showed a high compliance (92.5% presence at sessions) over the 8 weeks
      of exercise without any aggravation in disease status. They were able to train
      efficiently at moderate intensity up to 25 minutes. Significant improvements were
      found in locomotor ability, with a higher responsiveness measured by the
      locomotion biomechanical analysis, followed by the 6-minute gait test and the 50
      foot gait test. Inconsistent relationships between tests suggested that different
      locomotor abilities are required during tests. CONCLUSION: These results support
      the feasibility of a modified dance-based exercise program for persons with
      severe RA. With high levels of responsiveness, the detailed biomechanical
      analysis and the 6-minute gait test are recommended for the assessment of
      locomotor ability.

PMID- 14635284
TI  - Evaluation of health-related quality of life of rheumatoid arthritis patients
      treated with celecoxib.
AB  - OBJECTIVE: To study the functional status and health-related quality of life
      (HRQOL) of patients with rheumatoid arthritis (RA) after treatment with
      celecoxib, compared with placebo and naproxen. METHODS: This was a prospective,
      randomized, double-blind, parallel group trial conducted at 79 sites in the
      United States and Canada over a 12-week treatment period. Patients were randomly
      assigned to 5 groups: placebo, 100 mg twice a day of celecoxib, 200 mg twice a
      day of celecoxib, 400 mg twice a day of celecoxib, and 500 mg twice a day of
      naproxen. The Health Assessment Questionnaire (HAQ) disability index was used to
      measure functional status. The Medical Outcomes Study Short Form 36 (SF-36) was
      used to measure general HRQOL. RESULTS: Enrollees were 1,149 patients with
      diagnosed and active RA. At the end of the treatment period, patients in the 4
      active treatment groups had significant improvement in both functional status and
      overall HRQOL in comparison with the placebo group. Patients in the twice-daily
      100 mg celecoxib group significantly differed from placebo at weeks 2 and 6 on
      HAQ scores and at week 12 on 5 domains and both summary scores of the SF-36.
      Patients treated with twice-daily 200 mg celecoxib had significantly better
      functional status than placebo at all times of testing with the HAQ, and also had
      significantly better function than those treated with naproxen after 2 and 12
      weeks of treatment. Patients in the twice-daily 200 mg and 400 mg celecoxib
      groups showed similar improvement in HRQOL as determined by the 8 domain scores
      and 2 summary scores of the SF-36. CONCLUSION: Celecoxib was better than placebo
      and comparable with naproxen in improving functional status and overall HRQOL
      among RA patients.

PMID- 14635285
TI  - Historical perspective on the classification of vasculitis.

PMID- 14635287
TI  - Development and evaluation of a patient education program for persons with
      systemic sclerosis (scleroderma).
AB  - OBJECTIVE: To develop and evaluate the contents and disposition of a systemic
      sclerosis (SSc; scleroderma) patient education program. METHODS: Six women with
      SSc constituted the study group. Contents of the course were decided by the
      rheumatology team and were based on health assessments of the study participants
      made through medical examinations, measures of subjective symptoms, disability,
      physical and psychological function, and perceived self-efficacy, as well as the
      patients' opinions. The self-efficacy theory was used as the main theoretical
      basis for the education program. RESULTS: Both self-report and observer-scored
      measurements of disease impact and function were required to create the contents
      of the course. The patients reported that the professional medical information
      met their needs, although skin care and pain are topics that need additional work
      in the curriculum. The participants were satisfied with the program and the
      patient contacts, but found goal-setting to be an unfamiliar task. CONCLUSION:
      This pilot study of a multidisciplinary SSc education program fulfilled the
      general goals stated concerning the topics included and provided the opportunity
      for SSc patients to meet others with the same diagnosis. A larger study group is
      needed in order to analyze the effects of the course and the measurements used.

PMID- 14635286
TI  - Management and care of patients undergoing total knee arthroplasty: variations
      across different health care settings.
AB  - OBJECTIVES: To examine variation in the process of care for total knee
      arthroplasty (TKA) and to highlight the need for rigorous research into the ideal
      management of TKA. We hypothesize that variation in the process of care for TKA
      across and within health care systems is associated with identifiable financial
      and historical factors. METHODS: We compared access to TKA and typical
      postoperative rehabilitation management in 12 orthopedic centers in the United
      States (4 centers), United Kingdom (6 centers), and Australia (2 centers). We
      collected data from two sources: 1) Empirical data on length of stay and
      discharge management were collected as part of a prospective study of the
      outcomes of primary TKA for patients with a diagnosis of osteoarthritis; 2)
      Structured qualitative interviews were conducted at each of the participating
      centers to collect data on academic status and reimbursement structure, as well
      as waiting times for orthopedic consultation and TKA surgery once it had been
      scheduled. RESULTS: We demonstrated differences in length of acute hospital stay,
      use of extended care facilities, home physical therapy, and outpatient physical
      therapy within our cohort of hospitals. The publicly funded hospitals had a
      significantly longer acute hospital length of stay (mean 11.8 days, SD 7.1) than
      the private hospitals (mean 6.6 days, SD 4.1; P < 0.0001). Variation in waiting
      times was associated with the method of surgeon reimbursement and whether the
      hospital is publicly funded or private. Patients attending private hospitals
      waited 1-8 weeks for the first consultation and 2-12 weeks for a surgical date
      after scheduling. In contrast, patients attending publicly funded hospitals
      waited 4-12 months for a first consultation and 12-18 months for a surgical date
      after scheduling. CONCLUSIONS: Our observations are consistent with the
      hypothesis that financial reimbursement schemes influence the management of TKA.
      Further research needs to be done to quantify effects of varying processes of
      care on the outcome of TKA surgery across different health care settings. This
      data would elucidate the optimal management of TKA using objective evidence
      rather than relying on financial incentives or the preservation of historical
      practices.

PMID- 14635288
TI  - Marital satisfaction in couples with rheumatoid arthritis.
AB  - OBJECTIVE: To understand correlates of marital satisfaction in persons with
      rheumatoid arthritis (RA) and their spouses. METHODS: In a cross-sectional
      survey, 79 persons with RA and 78 spouses completed the Kansas Marital
      Satisfaction Scale, the revised Ways of Coping Questionnaire scales, and the
      Health Assessment Questionnaire. A series of linear regression analyses were then
      performed to investigate correlates of marital satisfaction for patients and
      spouses. RESULTS: Seventy-six percent of patients were women. Mean patient age
      was 56.5 years (+/- 12.5 years), number of years married was 30.7 (+/- 13.5), and
      duration of RA was 14.2 years (+/- 9.0 years). Demographic features of spouses
      resembled those of patients. Patients and spouses were generally satisfied with
      their marriages. Linear regression analyses showed that lower marital
      satisfaction in patients was associated with higher education level (P < 0.01),
      patient's greater use of escape into fantasy (P < 0.01), patient's greater use of
      finding blame (P < 0.05), and spouse's higher use of escape into fantasy (P <
      0.001). Spouses less satisfied with their marriages were more likely to use
      passive acceptance (P < 0.05) and less likely to find blame (P < 0.05). Female
      spouses were less likely to be satisfied in their marriages (P < 0.01) than male
      spouses. CONCLUSIONS: This study indicates that certain passive coping styles are
      associated with lower marital satisfaction in persons with RA and their spouses.
      More highly educated patients and female spouses are also less satisfied in their
      marriages. These cross-sectional correlations should not be regarded as causal
      and should be examined further in longitudinal studies.

PMID- 14635289
TI  - Symptoms of depression and psychological distress among Hispanics with rheumatoid
      arthritis.
AB  - OBJECTIVE: To explore the roles played by Hispanic ethnic background and
      acculturation to the mainstream English language culture of the United States in
      the depressive symptoms and mental health of rheumatoid arthritis (RA) patients.
      METHODS: Members of a consecutive cohort of patients with RA were studied cross
      sectionally. All underwent a comprehensive clinical and psychosocial evaluation.
      Depressive symptoms were measured with the Center for Epidemiologic Studies
      Depression Scale (CES-D), and psychological distress was measured with the
      Medical Outcomes Study Short Form 36 (SF-36) mental health scale. RESULTS: Two
      hundred thirty-six patients were studied. Women had significantly higher median
      CES-D scores than men (19 versus 14, P = 0.0004), Hispanics scored higher than
      non-Hispanics (14 versus 8, P = 0.0002), and foreign-born scored higher than US
      born patients (14 versus 10, P = 0.009). Compared with those who were fully
      acculturated, patients who were partially acculturated were more likely to have a
      score > or = 16 on the RA-adjusted CES-D (odds ratio [OR] = 1.79, 95% confidence
      interval [95% CI] 1.37 to 2.35, P < or = 0.001). Among unacculturated patients,
      the likelihood of a score > or = 16 increased 6-fold (OR = 6.68; 95% CI 3.50 to
      12.72; P < or = 0.001). A similar, inverse pattern was observed for the SF-36
      mental health scale. In multivariate models accounting for age, sex, education,
      income, articular pain, deformity, and the level of disability, low acculturation
      was independently associated with high depressive symptoms, and a Hispanic
      background was independently associated with lower SF-36 mental health.
      CONCLUSIONS: In this consecutive series of RA patients, Hispanics, particularly
      those who are not fully acculturated to the mainstream Anglo society, had more
      depressive symptoms and psychological distress than did non-Hispanics.

PMID- 14635290
TI  - The prevalence and impact of accommodations on the employment of persons 51-61
      years of age with musculoskeletal conditions.
AB  - OBJECTIVE: To provide estimates of the frequency with which persons 51 to 61
      years of age with musculoskeletal conditions receive workplace accommodations
      from their employers and to determine if the receipt of such accommodations is
      associated with higher rates of employment two years later. METHODS: The
      estimates derive from the Health and Retirement Survey, a national probability
      sample of 8,781 respondents who were interviewed both in 1992 and 1994 and who
      were between the ages of 51 and 61 years, of whom 5,495 reported one or more
      musculoskeletal conditions. We tabulated the frequency of accommodations provided
      in 1992 and then estimated the impact of accommodations and demographic and
      medical characteristics on 1994 employment status, using logistic regression.
      RESULTS: In 1992, about 14.40 million persons aged 51-61 years reported a
      musculoskeletal condition. Of these, 1.32 million (9.2%) reported a disability
      and were employed, the target population for accommodations. Overall, fewer than
      1 in 5 persons with musculoskeletal conditions who had a disability and were
      employed indicated that they had received any form of accommodation on their
      current jobs. Although no form of accommodation was reported with great
      frequency, the most commonly used ones included getting someone to help do one's
      job (12.1%), scheduling more breaks during the work day (9.5%), changing the time
      that the work day started and stopped (6.3%), having a shorter work day (5.6%),
      getting special equipment (5.3%), and changing the work tasks (5.3%). Persons
      with one or more accommodations in 1992, however, were no more likely to be
      working in 1994 than those with none. Only one specific accommodation--getting
      someone to help do one's job--was associated with a higher rate of employment in
      1994. CONCLUSIONS: Receipt of employment accommodations occurred infrequently,
      and was not generally associated with an improvement in the employment rate of
      persons with musculoskeletal conditions and disabilities.

PMID- 14635291
TI  - Clues to the pathogenesis of giant cell arteritis from the study of the vessel
      wall.

PMID- 14635292
TI  - Osteoarthritis treatment approaches, research methodologies, and agenda: do we
      need to re-invent the wheel?

PMID- 14635293
TI  - Perceptions about perceived functional disabilities and pain of people with
      rheumatoid arthritis: differences between patients and their spouses and
      correlates with well-being.
AB  - OBJECTIVE: In this study we examined the differences in perceptions of the
      patient's health status between rheumatoid arthritis (RA) patients and their
      spouses, and correlates of these differences with patients' and spouses' well
      being. METHODS: A sample of 188 couples with one member receiving treatment for
      RA were selected from the rheumatology clinics in Twente, The Netherlands. The
      mean age of both RA patients and spouses was 56 years. Respondents completed
      questionnaires, including estimations of both patients and spouses on the
      patient's functional disabilities and pain, and scales on affect and marital
      commitment for patients and spouses. RESULTS: Differences in estimations of
      patients and spouses were considerable. Both over- and underestimations of the
      patient's functional disabilities by the spouse were associated with the
      patient's poorer mental health status. Overestimations of the patient's
      functional disabilities were associated with poorer mental health among spouses.
      CONCLUSION: It is essential that any support intended by the spouse is in
      accordance with the patient's needs. If the patient's condition is misperceived
      by the spouse, this can lead to ineffective and inappropriate support being
      given.

PMID- 14635294
TI  - A pilot study on the effects of exercise in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: A pilot study was designed to assess the efficacy and safety of
      different exercise therapies on patient-reported fatigue and functional status.
      METHODS: Ten patients with systemic lupus erythematosus (SLE) were randomly
      placed in either an aerobic exercise group (group 1: n = 5) or a range of
      motion/muscle strengthening (ROM/MS) exercise group (group 2: n = 5). Outcome
      measures assessed at baseline and the end of the study were fatigue, functional
      status, disease activity, cardiovascular fitness, isometric strength, bone
      mineral density (BMD) of the lumbar spine and femoral neck, and parathyroid
      hormone and osteocalcin as representative bone biochemical markers for bone
      resorption and bone formation, respectively. RESULTS: Both aerobic and ROM/MS
      types of exercise were safe and did not worsen SLE disease activity. Patients in
      both exercise groups showed some improvement in fatigue, functional status,
      cardiovascular fitness, and muscle strength. Both groups showed increased bone
      turnover, but BMD was unchanged. Eighty percent of the patients met the
      compliance standard for the study. CONCLUSIONS: This pilot study shows the
      feasibility of exercise for SLE patients. The potential value of this approach
      shows promise in the routine management of these patients.

PMID- 14635295
TI  - Physical function among older adults with knee pain: the role of pain coping
      skills.
AB  - OBJECTIVE: To evaluate the association between pain coping skills and disability
      among older adults with knee pain. METHODS: Baseline measures from 394 older
      adults with knee pain and disability who participated in a 30-month observational
      study were analyzed. Pain coping skills were correlated with self-reported
      disability and walking distance after controlling for covariates of disability.
      RESULTS: Pain coping skills were significantly associated with disability (P <
      0.05) and distance walked (P < 0.05). Less catastrophic thinking and prayer,
      greater ignoring and reinterpretation of pain sensations, and stronger
      perceptions of pain control were associated with less disability and better
      physical function. CONCLUSION: Pain coping skills used by older adults with
      osteoarthritis and knee pain may play a significant role in determining
      disability.

PMID- 14635296
TI  - Comparison of the responsiveness of symptomatic outcome measures in knee
      osteoarthritis.
AB  - OBJECTIVE: A number of international scientific societies have recommended a core
      set of domains to be systematically assessed in clinical research studies on
      osteoarthritis (OA), i.e., pain, function, and patient's overall assessment. This
      open, longitudinal, observational study compares the responsiveness of different
      symptomatic variables evaluating these 3 domains in knee OA. METHODS: Patients
      were individuals with painful knee OA. The collected data were Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (0-100) and
      WOMAC function subscale (0-100), Lequesne's index (0-100), pain after physical
      activities (visual analog scale [VAS] 100 mm), and patient's global assessment
      (VAS 100 mm). The procedure used was knee joint lovage. Time of collection was
      before and 1, 3, and 6 months after the lavage. Analysis was by comparison of the
      standardized response mean (mean of the changes/SD of the changes) in an intent
      to-treat strategy after 1, 3, and 6 months using the jackknife method. RESULTS:
      Improvement in all dimensions of WOMAC subscale scores and VAS scores was
      observed at month 1. Lequesne's index was not responsive to change. The
      standardized response mean was moderate, ranging from 0.00 to 0.40. Comparison of
      the estimates of the standardized response means using the jackknife method
      showed a statistically significant difference between Lequesne's index and the
      WOMAC subscale for function, but not between VAS pain and the WOMAC subscale for
      pain. CONCLUSION: Most of the evaluated variables have a moderate responsiveness.
      In knee OA, the WOMAC function scale seems to be more sensitive than Lequesne's
      index for detecting changes after symptomatic therapy.

PMID- 14635298
TI  - Reliability of the six-minute walk test in people with fibromyalgia.
AB  - OBJECTIVE: To determine the test-retest reliability of the 6-minute walk test in
      people with fibromyalgia. METHODS: Twenty-six subjects (27-59 years of age)
      performed 3 walk tests over consecutive days before and after a 4-week treatment
      program. Reliability was determined using a one-way repeated measures analysis of
      variance and the intraclass correlation coefficient (ICC2,1). RESULTS:
      Reliability of the 6-minute walk test was excellent both at program intake
      (ICC2,1 = 0.91) and program completion (ICC2,1 = 0.98). On program intake,
      significant differences (P < 0.01) were found between test 1 (478 +/- 61 m) and
      test 2 (492 +/- 57 m), and between test 1 and test 3 (495 +/- 60 m). On program
      completion, there were no significant differences across the 3 replicate tests
      (507 m, 505 m, and 509 m). CONCLUSIONS: The 6-minute walk test is a reliable
      measure in people with fibromyalgia. In this study, two trials were required to
      achieve a stable walk performance before a treatment program. This learning
      effect was not present following the intervention.

PMID- 14635297
TI  - Vessel wall morphometry in giant cell arteritis.
AB  - OBJECTIVE: To investigate morphometrically the relationship between the degree of
      inflammatory reaction and arterial cross-sectional dimensions in giant cell
      arteritis (GCA). METHODS: The media and intima of cross-sectioned inflamed
      arteries from GCA patients were outlined. The media circumference and the media
      and intima cross-sectional areas were measured. The two segments in every biopsy
      displaying the least and most widespread media inflammation were compared, using
      a paired Student's t-test. Moreover, paired comparisons were made of the intima
      area in inflamed and noninflamed sectors in single cross-sections. RESULTS: The
      segment in each biopsy showing the most widespread media inflammation had the
      largest circumference and volume of media and intima; the intima cross-sectional
      area increased disproportionately. The intima was thickest in inflamed sectors in
      single cross-sections. CONCLUSION: The close spatial correlation between
      inflammatory media infiltration and the marked intimal expansion supports the
      contention that promoting factors produced by inflammatory cells play a
      pathogenetic role in GCA.

PMID- 14635299
TI  - The ability of the Cochin rheumatoid arthritis hand functional scale to detect
      change during the course of disease.
AB  - OBJECTIVE: To assess changes measured with the Cochin rheumatoid arthritis (RA)
      hand functional disability scale during the course of the disease. METHODS: A
      cohort study evaluating outcome measure responsiveness in RA was conducted in a
      referral center. Ambulatory or hospitalized patients with RA according to the
      1987 American College of Rheumatology (formerly the American Rheumatism
      Association) criteria were evaluated twice. Clinical measures included Cochin's
      scale, Revel's functional index, hand functional index, visual analog scale of
      patient-perceived handicap, visual analog scale of pain in hands and wrists,
      total score of swelling, total score of tenderness, and morning stiffness
      duration. Responsiveness was assessed by the effect size (ES) and the
      standardized response mean (SRM). The nonparametric Spearman rank correlation
      coefficient (r) was used to assess the correlation between two quantitative
      variable changes. RESULTS: Fifty-five patients (44 women) were evaluated twice at
      an interval of 15.4 +/- 1.4 months (mean +/- SD) (range 13-18 months). The Cochin
      scale total score had worsened at the second visit (95% confidence interval for
      mean differences -5.16, 0.73). Its SRM and ES values were -0.20 and -0.15,
      respectively. Changes in the score had the highest correlation (r = 0.58) with
      changes in the patient-perceived handicap, while it had only fair or little
      correlation with changes in the disease activity measures. The factor 2 scale
      subscore significantly worsened and had the highest values of SRM and ES (SRM = 
      0.40 and ES = -0.31). CONCLUSION: The Cochin scale can detect small but
      meaningful changes in RA hand disability.

PMID- 14635300
TI  - A pilot study of body awareness programs in the treatment of fibromyalgia
      syndrome.
AB  - OBJECTIVE: To compare in a pilot study the effect of two physical therapies, the
      Mensendieck system (MS) and body awareness therapy (BAT) according to Roxendal,
      in fibromyalgia patients and to investigate differences in effect between the two
      interventions. METHODS: Twenty female patients were randomized to either MS or
      BAT in a program lasting 20 weeks. Evaluations were tender point examination and
      questionnaires, including visual analog scales (pain intensity at worst site,
      muscular stiffness, evening fatigue, and global health), Fibromyalgia Impact
      Questionnaire (FIQ), Coping Strategies Questionnaire, Quality of Life Scales,
      Arthritis Self-Efficacy Scale (ASES), and disability before, immediately after,
      and at 6 and 18 months follow-up. RESULTS: The BAT group had improved global
      health at 18 months follow-up, but lower results than the MS group. The MS group
      had improved FIQ, ASES other symptoms, and pain at worst site at 18 months follow
      up. CONCLUSION: In the present pilot study, MS was associated with more positive
      changes than BAT.

PMID- 14635301
TI  - Exploring the priorities of patients with osteoarthritis of the knee.
AB  - OBJECTIVE: To explore the perceived importance of symptoms, treatment
      preferences, and research priorities of people with osteoarthritis (OA) of the
      knee. METHODS: Results of a focus group were used to facilitate the design of a
      questionnaire, distributed to 112 people with knee OA. RESULTS: Pain, disability,
      and instability in the joint were the most important symptoms, and anxiety about
      knee OA caused distress to many people. Oral drugs (90%), physical therapy (62%),
      and aids and adaptations (56%) were the most commonly used treatments. Surgery,
      oral drugs, and intra-articular injections were perceived as the most efficacious
      interventions. Patients' highest priorities for research were surgery and
      educational interventions, despite the fact that few had had surgery and
      education was not perceived as very effective. CONCLUSIONS: The lack of a patient
      centered approach to care leads professionals to ignore key symptoms and issues
      for individuals, and to a preoccupation with pharmaceutical interventions, rather
      than the treatment options that their patients prefer.

PMID- 14635302
TI  - Audience motivations to use an arthritis website.

PMID- 14635303
TI  - The effects of bone density testing at health fairs on awareness and treatment of
      osteoporosis.

PMID- 14635304
TI  - Proximal symphalangism associated with conductive hearing loss.

PMID- 14635305
TI  - Late onset hypersensitivity to sulfasalazine in a patient with ankylosing
      spondylitis: comment on the article by Paul et al.

PMID- 14635306
TI  - Classification of vasculitis: comment on the review by Matteson.

PMID- 14635308
TI  - Use of ANCA in diagnosis.

PMID- 14635309
TI  - Fibromyalgia, physical activity, and daily functioning: the importance of
      efficacy and health-related quality of life.
AB  - OBJECTIVE: To determine whether individuals with fibromyalgia (FM) who are more
      physically active differ in various psychosocial characteristics (i.e., self
      efficacy, health-related quality of life [HRQL]) from those who are less active,
      and whether those who function better on a daily basis also differ in these
      characteristics from their less able counterparts. METHODS: The predominantly
      female sample (n = 86) consisted of individuals medically diagnosed with FM.
      Measures included symptom variables, physical activity frequency and intensity,
      daily functioning, HRQL, efficacy for physical activity, FM pain, and other FM
      symptoms. RESULTS: Discriminant function analyses to predict physical activity
      status (P < 0.0001) and functional ability status (P = 0.03) were significant.
      The variables of physical activity efficacy, pain efficacy, and the physical HRQL
      component were the best predictors. CONCLUSION: Support for the importance of
      perceived control and HRQL for engaging in higher levels of physical activity and
      daily functioning was demonstrated. Future research must continue to examine
      psychosocial factors that affect patients' functioning with FM in order to
      enhance their well-being.

PMID- 14635310
TI  - The effect of static traction and orthoses in the treatment of knee contractures
      in preschool children with juvenile chronic arthritis: a single-subject design.
AB  - OBJECTIVE: External applied devices are sometimes used in the treatment of
      persistent knee contractures in juvenile chronic arthritis (JCA). This study
      examined the effect of static night traction and orthoses on passive and active
      extension range of motion (ROM) in preschool children with JCA. METHOD: A single
      subject design was used, comparing the outcome of periods without intervention
      (A) with that of periods with intervention in the form of traction and orthoses
      (B). Five patients, 3 girls and 2 boys, participated. Active and passive
      extension ROM was measured weekly. The data were examined by visual inspection of
      trend, slope, and mean level in each period. RESULTS: Greater improvement in both
      active and passive extension ROM was seen in the B periods than in the A periods.
      The intervention was not observed to have any negative effects on the children.
      CONCLUSION: Static night traction may be a useful supplement to physiotherapy and
      medication to reduce knee flexion contractures in small children with JCA. The
      effect of the orthoses was difficult to evaluate because they were used for an
      insufficient time.

PMID- 14635311
TI  - The economic impact of intermittent high-dose intravenous versus oral
      corticosteroid treatment of juvenile dermatomyositis.
AB  - OBJECTIVE: To perform a cost-identification and cost-effectiveness analysis
      comparing oral corticosteroids (OCS) with high-dose intermittent intravenous
      corticosteroid (IVCS) regimens in the treatment of juvenile dermatomyositis
      (JDM). METHODS: Children previously diagnosed and treated for JDM (without
      myositis-specific or myositis-associated autoantibodies) at a single medical
      center by a single provider were identified. Two treatment protocols were
      compared: OCS and IVCS. Data on initial disease severity, time to remission,
      resource use, and costs generated were collected from patient records.
      Incremental cost-effectiveness ratios (ICE) were constructed. RESULTS: Patients
      treated with IVCS achieved median remission 2 years earlier at median increased
      cost of $13,736. The ICE ratio comparing IVCS to OCS is $6,868 per year of
      disease avoided. CONCLUSION: This study suggests that, although IVCS treatments
      are costly, they are cost-effective.

PMID- 14635312
TI  - Hand Mobility in Scleroderma (HAMIS) test: the reliability of a novel hand
      function test.
AB  - OBJECTIVE: Hand Mobility in Scleroderma (HAMIS) is a new hand function test
      developed for adults who have systemic sclerosis. HAMIS consists of 9 items
      designed to measure all movements assessed in an ordinary range of motion (ROM)
      measured hand test. The aim of this study was to examine the reliability of the
      test. METHODS: Two observers (one occupational therapist and one physiotherapist)
      performed the assessments independently of each other on 30 adult subjects. There
      were 25 women and 5 men in the sample (mean age 53 years, average time since
      diagnosis 4 years). Subjects were tested twice by each rather. RESULTS: Internal
      consistency ranged from 0.80 to 0.85 (Cronbach's alpha). Agreement between the
      two observers was good for all items (estimated kappa 0.52 to 1.00). The
      agreement between the observers' first and second assessments was moderate to
      very good for most items (estimated kappa 0.48 to 1.00), but not for the
      assessment of supination (estimated kappa 0.25 to 0.59). CONCLUSION: HAMIS is a
      reliable instrument for evaluation of hand function on scleroderma patients.

PMID- 14635313
TI  - Displacement response of juvenile arthritic wrists during grasp.
AB  - OBJECTIVE: To analyze the displacement response of juvenile arthritic wrists
      during grasp in order to diagnose early ligamental laxity and facilitate early
      splinting. METHODS: X-rays of the wrists, made under standardized conditions, of
      30 children with juvenile chronic arthritis (mean age 10.4 years, range 4.5-16.9)
      were analyzed after being digitalized. Osseous landmarks were identified, and
      coordinates were calculated from measured angles and lengths with an accuracy of
      0.01'. Lunate and carpal-ulnar distance were obtained according to Youm, and
      ulnar variance according to Hafner. RESULTS: Overall, an increase in ulnar-lunate
      displacement and carpal narrowing and a decrease in ulnar variance were found.
      However, not all wrists responded to the same extent. Radial displacement of the
      lunate, though slight, was found in 2 wrists and the amount of ulnar displacement
      varied substantially (3.1% to 22.5%). The variance in amount of displacement
      could suggest that juvenile wrists do not respond to increased compressive forces
      to the same extent. CONCLUSION: The changes found are similar to those found in
      the healthy wrist. Furthermore, our findings suggest that the juvenile wrist acts
      in accordance with the generally accepted explanation for the development of
      malalignment in adult wrists. It seems that laxity of ligaments can be diagnosed
      early by the force grip maneuver during x-ray. It would have a significant impact
      on the moment of orthotic intervention as well as the design of the orthotic
      device. Further study along this line seems justified.

PMID- 14635314
TI  - Validity of HAMIS: a test of hand mobility in scleroderma.
AB  - OBJECTIVE: Hand Mobility in Scleroderma (HAMIS) is a hand function test for
      persons who have systemic sclerosis (scleroderma). The purpose of HAMIS is to
      obtain an estimation of the hand mobility that is precise enough to detect
      limitation of motion at the same time as it indicates the ability to use the hand
      in daily occupations. The aim of this study was to test psychometric properties
      of the HAMIS, and the following aspects of HAMIS were examined: 1) the
      applicability of HAMIS, 2) concurrent validity, and 3) discriminating ability.
      METHODS: Forty-five patients with scleroderma were assessed for range of motion
      (ROM), HAMIS, and skin thickness. In addition, 15 healthy individuals completed
      HAMIS. RESULTS: The applicability of HAMIS was good for items assessing finger
      and thumb mobility and moderate for items assessing mobility of the wrist and the
      forearm. The relationships of HAMIS to ROM and skin score were statistically
      significant for all items except for pronation and supination of the forearm.
      There were also statistically significant differences between the patients and
      the healthy individuals for all items except these two. CONCLUSION: HAMIS has a
      demonstrated concurrent validity compared with ROM and skin score, and it showed
      a good ability to discriminate between healthy individuals and persons with
      scleroderma, although a lack of variation in the items measuring pronation and
      supination inferred worse psychometric properties for these two items.

PMID- 14635315
TI  - A review of biobehavioral research in juvenile primary fibromyalgia syndrome.

PMID- 14635316
TI  - The effects of weight reduction on the rehabilitation of patients with knee
      osteoarthritis and obesity.
AB  - OBJECTIVE: To evaluate the effect of weight reduction on the rehabilitation of
      patients with knee osteoarthritis and obesity. METHODS: A total of 126 patients
      with bilateral knee osteoarthritis and obesity were classified into 3 groups by
      their stages of osteoarthritis. Each group was divided into subgroups a, b, and
      c. The subjects in subgroup a received weight reduction treatment, those in
      subgroup b received weight reduction and electrotherapy modalities, and those in
      subgroup c received electrotherapy modalities to relieve pain. RESULTS: Pain
      reduction, weight reduction, ambulation speed, and changes of Lequesne's index
      were greater in patients in subgroups a and b than in subgroup c after treatment.
      Although the last pain scores in subgroup b were less than those in subgroup a,
      as measured by a visual analog scale (VAS), there was no significant difference
      between their functional status. Significant pain relief (VAS < 2) and an
      acceptable functional status (Lequesne's index < 7) were indicated when weight
      reduction was more than 15% and 12%, respectively, of the initial body weight of
      the individual. CONCLUSION: Weight reduction was found to be a practical adjuvant
      treatment in the rehabilitation of patients with knee osteoarthritis.

PMID- 14635317
TI  - Factors associated with refractory renal disease in patients with systemic lupus
      erythematosus: the role of patient nonadherence.
AB  - OBJECTIVE: To assess the prevalence and underlying reasons for the development of
      chronic renal insufficiency (CRI) in patients with systemic lupus erythematosus
      (SLE) seen over a 3-year period in our lupus clinic, in particular to determine
      the frequency and types of patient-dependent factors that were associated with
      nonadherence when it occurred. METHODS: We determined the frequency and types of
      patient-dependent factors that were associated with the development of CRI in
      patients with SLE. CRI was defined as a serum creatinine level > or = 200 mumol/l
      for at least 6 months. RESULTS: Of the 462 patients followed at the lupus clinic
      between 1995 and 1998, 17 patients developed CRI. Patient-related factors were
      deemed to be the major reason for the development of CRI in 5 of these. Three of
      the 5 patients were nonwhite, and the 2 patients who were white were new
      immigrants. All 5 patients were reluctant to take high-dose corticosteroids
      because of potential adverse effects. Financial problems contributed to
      nonadherence in 2 cases. Two patients refused to continue steroids and
      immunosuppressive therapy and chose to use "alternative" medications as their
      sole therapy. Of these 5 patients, 3 are now on long-term renal replacement
      therapy, 1 has died, and 1 patient continues to be followed with a serum
      creatinine level of 250 mumol/l. CONCLUSION: There is a need for an educational
      program based on patients' cultural background in order to enhance patients'
      understanding of the aims, risks, and benefits of therapy in SLE.

PMID- 14635318
TI  - Prevalence of arthritis in older Mexican Americans.
AB  - OBJECTIVE: This study examines the prevalence of self-reported physician
      diagnosed arthritis and arthritis symptoms and their relationship to functional
      limitations in Mexican American elderly. METHODS: We conducted a cross-sectional
      study using a probability sample of 2,873 non-institutionalized Mexican American
      men and women aged 65 or older, residing in the southwestern United States.
      Measures included self-reported physician-diagnosed arthritis, morning pain or
      stiffness, pain when standing, global health rating, activities of daily living
      (ADL), instrumental activities of daily living (IADL), depressive symptoms,
      presence of chronic diseases (diabetes mellitus, hypertension, heart attack,
      stroke), and body mass index. The Mantel-Haenszel chi-square statistic was used
      to test differences by arthritis status, and a logistic regression model was used
      to predict the odds of having arthritis. RESULTS: The overall prevalence of self
      reported physician-diagnosed arthritis in the sample was 40.8 percent, 50.0
      percent among women and 28.8 percent among men (P < 0.001). Morning pain or
      stiffness was reported by 37.7 percent of respondents and pain when standing or
      walking by 31.9 percent. All comorbid conditions, and both IADL and ADL
      limitations, were more prevalent in those with arthritis than in those without
      arthritis. Female sex and several medical conditions were independently
      associated with self-reported arthritis. CONCLUSIONS: Self-reported physician
      diagnosed arthritis is common among older Mexican Americans. Functional
      limitation and disability are more prevalent among subjects with arthritis than
      among those without arthritis.

PMID- 14635319
TI  - Temporal concurrence of vasculitis and cancer: a report of 12 cases.
AB  - OBJECTIVE: Vasculitis has been associated with solid organ and hematologic
      cancer. The rarity of these associations, and in many reports the lack of
      temporal relationships, has led to skepticism about vasculitis being a
      paraneoplastic syndrome. The objective of the present study was to review cases
      of concurrent vasculitis and cancer at the Cleveland Clinic Foundation over an
      18.5-year period and explore evidence that would support the notion of vasculitis
      being a type of paraneoplastic disease. METHODS: Retrospective review of the
      records of all patients diagnosed with vasculitis and cancer within 12 months of
      each other was performed using an ICD-9 diagnostic data base at the Cleveland
      Clinic Foundation. Patients with known chronic autoimmune disease or serologic
      evidence of hepatitis B or C infection were excluded. A standardized data
      collection instrument was used to document information about presentation,
      treatment, and course of illness. RESULTS: During the 18.5 years of our study,
      more than 15 million inpatients and outpatients were seen at the Cleveland
      Clinic. Of these, 2,800 patients had vasculitis independent of cancer, more than
      69,000 patients had cancer, and 69 patients had been identified who had both
      malignancies and systemic vasculitis. Only 12 patients were identified in whom
      both vasculitis and cancer occurred within the same 12 months. Mean age was 65
      years (range 45-79). There was no gender preference (M = F). In 8 of the 12
      cases, diagnoses were made within 3 months of each other. In 6 of the patients,
      the diagnoses of both processes were made within 1 month. Ten of the 12 patients
      had vasculitis 1 to 3 months prior to or concurrent with the diagnosis of cancer.
      Six of the 12 patients had solid organ tumors, 4 had lymphoma, 1 had leukemia,
      and 1 had multiple myeloma. The most common vasculitis was cutaneous
      leukocytoclastic vasculitis (LCV), which occurred in 7 cases. Four cases of LCV
      were associated with solid organ tumors. Other vasculitides included giant cell
      arteritis (n = 2), polyarteritis nodosa (n = 2), and Wegener's granulomatosis (n
      = 1). The response of the vasculitis to glucocorticoid and cytotoxic therapy
      varied. Complete remission of vasculitis occurred in 4 of the patients, partial
      improvement occurred in 4 patients, and no improvement was noted in 4 patients.
      Complete remission occurred in 3 of the 4 patients in whom vasculitis and cancer
      were treated concurrently. Eight of 10 patients in whom followup was greater than
      2 months demonstrated concordance of disease activity and treatment response for
      both cancer and vasculitis. CONCLUSION: The close temporal relationship of cancer
      and vasculitis in our patients adds to circumstantial evidence of vasculitis at
      times being a paraneoplastic condition. Failure of a vasculitis to respond to
      conventional therapy should raise questions about underlying malignancy.
      Effective treatment of the cancer enhances the likelihood of improvement in
      vasculitis.

PMID- 14635320
TI  - Test characteristics of immunofluorescence and ELISA tests in 856 consecutive
      patients with possible ANCA-associated conditions.
AB  - OBJECTIVE: To examine the test characteristics of immunofluorescence (IF) and
      enzyme-linked immunosorbent assays (ELISA) in a consecutive series of patients
      under evaluation for anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV). METHODS: Using stored sera, we performed a cross-sectional
      study on 856 consecutive patients tested prospectively for ANCA by IF, Based on
      guidelines from the 1994 Chapel Hill Consensus Conference (CHCC), we determined
      each patient's underlying diagnosis by a medical records review without regard to
      their ANCA status (the CHCC guidelines do not require ANCA as a prerequisite for
      diagnosis). We grouped patients with forms of vasculitis commonly associated with
      ANCA into one of 4 types of AAV: Wegener's granulomatosis (n = 45), microscopic
      polyangiitis (n = 12), Churg-Strauss syndrome (n = 4), and pauci-immune
      glomerulonephritis (n = 8). We also classified patients without clinical evidence
      of AAV (92% of all patients tested) into 5 predefined categories of disease
      (including "other") and an additional category for no identifiable disease. In a
      blinded fashion, we then performed ELISAs on the stored serum for antibodies to
      proteinase-3 (PR3) and myeloperoxidase (MPO) and calculated the test
      characteristics for both ANCA assay techniques. RESULTS: Sixty-nine of the 856
      patients (8.1%) had clinical diagnoses of AAV based on CHCC guidelines. The
      positive predictive value (PPV) of ELISA for AAV was superior to that of IF, 83%
      versus 45%. For patients with both positive IF tests and positive ELISA tests,
      the PPV increased to 88%. Both IF and ELISA had high negative predictive values
      (97% and 96%, respectively). Positive ELISA tests were associated with higher
      likelihood ratios (LR) than IF (54.2 [95% CI = 26.3, 111.5] versus 9.4 [95% CI =
      6.9, 12.7]). The LR of both a positive IF and a positive ELISA was 82.1 (95% CI =
      33.3, 202.5). CONCLUSIONS: Compared with IF, an ELISA test fo ANCA was associated
      with a substantially higher PPV and LR for AAV. This fact, combined with the
      greater sensitivity of IF, suggests that an effective testing strategy is to
      perform ELISA tests only on samples that are positive for ANCA by IF.

PMID- 14635321
TI  - Stress management in rheumatoid arthritis: what is the underlying mechanism?
AB  - OBJECTIVE: To test whether change in cognitive-behavioral variables (such as self
      efficacy, coping strategies, and helplessness) is a mediator in the relation
      between cognitive behavior therapy and reduced pain and depression in persons
      with rheumatoid arthritis (RA). METHODS: A sample of patients with RA who
      completed a stress management training program (n = 47) was compared to a
      standard care control group (n = 45). A path analysis testing a model including
      direct effects of comprehensive stress management training on pain and depression
      and indirect effects via change in cognitive-behavioral variables was conducted.
      RESULTS: The path coefficients for the indirect effects of stress management
      training on pain and depression via change in cognitive-behavioral variables were
      statistically significant, whereas the path coefficients for the direct effects
      were found not to be statistically significant. CONCLUSION: Decreases in pain and
      depression following stress management training are due to beneficial changes in
      the arenas of self-efficacy (the belief that one can perform a specific behavior
      or task in the future), coping strategies (an individual's confidence in his or
      her ability to manage pain), and helplessness (perceptions of control regarding
      arthritis). There is little evidence of additional direct effects of stress
      management training on pain and depression.

PMID- 14635322
TI  - The engineering of whiplash: a clinician's work is never done.

PMID- 14635323
TI  - [Research on prehospital and emergency care--a necessity with difficult
      conditions].

PMID- 14635324
TI  - [Prehospital recording of vital parameters in injured patients].

PMID- 14635325
TI  - [Treatment of critically ill patients during interhospital transport].

PMID- 14635326
TI  - [Initial treatment of patients with unstable pelvic fractures and hemorrhagic
      shock].

PMID- 14635327
TI  - [Severe hypothermia].

PMID- 14635328
TI  - [Mortality among severely injured patients before and after establishment of a
      trauma center in Aarhus].

PMID- 14635329
TI  - [Prehospital endotracheal intubation of critically injured patients].

PMID- 14635330
TI  - [Recommendations for basic life support in Denmark. Comparison with international
      guidelines].

PMID- 14635331
TI  - [Subcutaneous emphysema, atrial flutter and precordial chest pain following nose
      blowing after jaw surgery].

PMID- 14635332
TI  - [Management of suspected cervical column fracture].

PMID- 14635333
TI  - [Orientation from the Danish Committee for Resuscitation. Recommendations
      concerning ventilation methods in basic resuscitation of adults].

PMID- 14635334
TI  - [Mouth-to-mouth resuscitation recommended on unscientific basis].

PMID- 14635335
TI  - [Is repeat antibiotic prescription following treatment with sulfonamide or
      pivmecillinam a valid method for assessment of therapeutic failure in urinary
      infection?].

PMID- 14635337
TI  - [Have the counties followed recommendations by the National Board of Health and
      Welfare concerning the number of MR-scanners and CT-scanners?].

PMID- 14635336
TI  - [Sulfamethizole versus pivmecillinam in urinary tract infections].

PMID- 14635338
TI  - [New thinking and COPD].

PMID- 14635339
TI  - Enhancing end-of-life: oncology nurses can be effective change agents.

PMID- 14635340
TI  - The West Nile virus: an emerging public health challenge.

PMID- 14635341
TI  - Further discussion of NRRs.

PMID- 14635342
TI  - Four keys to instilling innovation and creativity.

PMID- 14635343
TI  - Virtual lifesaving.

PMID- 14635345
TI  - Tutorial on field instrumentation.

PMID- 14635344
TI  - Failure to train employees--now a federal crime.

PMID- 14635346
TI  - Interpreting OSHA's new APF proposal.
AB  - The new proposal from OSHA clarifies much of the longstanding confusion about the
      protection factor ratings of the respirators that employers and workers rely upon
      for protection in hazardous atmospheres. Almost irrespective of its final
      content, this new rule, once promulgated, will become the authoritative source
      for respirator Assigned Protection Factors and ease the burden of health and
      safety professionals who ministration of respiratory protection in the workplace.

PMID- 14635347
TI  - Let's clear the air on respiratory protection.

PMID- 14635348
TI  - Achieving voice & data interoperability.

PMID- 14635349
TI  - Fatal occupational injuries involving confined spaces, 1997-2001.

PMID- 14635350
TI  - Calibration requirements for confined space gas detectors.

PMID- 14635351
TI  - Preventing shock with proper grounding techniques.

PMID- 14635352
TI  - Effective use of PPE.

PMID- 14635353
TI  - Torn over training?

PMID- 14635354
TI  - Improved documentation.

PMID- 14635355
TI  - Germ warfare, or, how I survived the plague ship.

PMID- 14635356
TI  - Blackout! Is Tennessee healthcare prepared?

PMID- 14635357
TI  - TMA President's project: Dr. Ali takes on cancer screening.

PMID- 14635358
TI  - Loss prevention case of the month. Deadly lifestyle--physician pays anyway.

PMID- 14635359
TI  - Constrictive pericarditis following cat-scratch disease in a 12-year-old female:
      a rare association.
AB  - We are reporting an unusual case of cat-scratch disease in a young adolescent
      girl presenting with recurrent ascites. The illness started with nonspecific
      symptoms followed by ascites and an axillary lymph node enlargement. She had
      recurrent ascites for 18 months associated with constrictive pericarditis.
      Following pericardiectomy, she had a resolution of ascites and was back to her
      normal life. This is a first documented report of a constrictive pericarditis
      following cat scratch diseases in English literature.

PMID- 14635360
TI  - Successful treatment of childhood spasticity secondary to cerebral palsy using
      Botox.
AB  - Spasticity resulting from cerebral palsy can reduce the quality of life in
      affected children and can eventually cause more severe impairments, such as joint
      dislocation and scoliosis. Botulinum toxin type A (Botox) is widely used to
      temporarily alleviate the increased muscle tone associated with spasticity, and
      when combined with a comprehensive physical therapy regimen can result in
      permanent improvement. This report documents the successful use of Botox over a
      two-year period to treat spasticity secondary to cerebral palsy in a preschool
      age child. Botox was used in conjunction with a specific physical therapy regimen
      in order to reach a functional goal of independent ambulation.

PMID- 14635361
TI  - The execution of wills for patients with Alzheimer's disease: the physician's
      role in "incapacity" and "undue influence".

PMID- 14635362
TI  - Diabetes detection and primary prevention.

PMID- 14635363
TI  - The inotropic therapy of decompensated heart failure revised. Introduction.

PMID- 14635364
TI  - The current therapeutic approach to chronic heart failure.
AB  - In the past 20 years, enormous progress has been made in the understanding of the
      pathophysiology and treatment of the complex clinical syndrome of heart failure.
      It has been a bidirectional process, with improvements in the understanding of
      the pathophysiology suggesting new therapeutic approaches and the success and
      failures of clinical trials refining our hypotheses or even suggesting the
      involvement of new pathophysiological mechanisms. In the past, heart failure was
      interpreted on the basis of a pathophysiological model according to which the
      hemodynamic abnormalities played a key role in determining the clinical
      presentation and the evolution of the disease. Therefore, the objective of
      pharmacological treatment was to improve these hemodynamic abnormalities. At the
      beginning of the '90s it became clear that the activation of the reninangiotensin
      aldosterone system and of the sympathetic system caused by the abnormality in
      cardiac function had deleterious clinical effects in the long term. Heart failure
      was therefore considered as a "neurohormonal" disorder and the objective of
      pharmacological treatment was to improve survival by antagonizing this reflex
      activation. More recently, even the so-called "neurohormonal" hypothesis has
      itself evolved in several ways. In the present review the efficacy of each class
      of drug will be discussed in the light of the results of the most important
      clinical trials. In fact, from a practical point of view, since we learned so
      much from the published trials, it is very important that we know how these have
      been structured to evaluate the applicability of pharmacological treatments to
      individual patients.

PMID- 14635365
TI  - Infusion therapy in severe heart failure. A reappraisal.
AB  - Decompensated heart failure is associated with high rates of morbidity and
      mortality and it is responsible for numerous hospitalizations. The current
      approach to acute exacerbations is based on diuretics, vasodilators and
      inotropes. Compared with the impressive development of new therapeutic agents
      designed for other cardiovascular diseases, little progress has been observed in
      developing new drugs for the treatment of decompensated heart failure. Moreover,
      a series of controlled clinical trials failed to show a better outcome or a
      reduction in morbidity during treatment with inotropes, even though promising
      results were recently observed in controlled clinical trials with new classes of
      drugs, such as calcium sensitizers and nesiritide; these agents will probably
      modify the treatment options of decompensated heart failure in the coming years.

PMID- 14635366
TI  - Inotropic therapy is unsuccessful: wrong conceptual target or wrong therapeutic
      tools?
AB  - Since a depressed contractility has long been considered the primary defect in
      patients with heart failure, the use of inotropic agents has been regarded as a
      logical approach to treat this syndrome. Despite this conceptual framework, these
      drugs have not yet established themselves in the treatment of chronic heart
      failure and their long-term use was associated with an excessive mortality while
      the short-term intravenous administration in critically ill patients produced
      only acute hemodynamic results without a stable clinical improvement. At least
      four mechanisms could explain this discrepancy: their arrhythmogenicity, their
      direct cardiotoxic effects, the downregulation of the beta-adrenoreceptors, and
      the energetic cost of inotropic intervention. Moreover, in many patients with
      ischemic cardiomyopathy the reduction in contractility could be considered as a
      compensatory mechanism since hibernation is able to decrease the metabolic
      requirements of the heart. The contractile force of the heart can be augmented
      not only by an increased availability of intracellular calcium for troponin C but
      also by an increased sensitivity of the contractile proteins to calcium. A new
      class of inotropes working with this mechanism is now available and could
      represent a real improvement in this challenging therapeutic area.

PMID- 14635367
TI  - Is calcium sensitization the best strategy to improve myocardial contractility in
      acute heart failure?
AB  - The finely-tuned increases and decreases in the intracellular calcium levels in
      myocytes ultimately regulate the contraction and relaxation of the heart.
      Therapeutic agents can improve or interfere with this delicate balance. Calcium
      sensitizers enhance cardiac contraction by improving the use of calcium that is
      available, rather than by inundating the cell with excessive calcium, as is the
      case with traditional inotropes. With the sensitizing mechanism, the energy cost
      of contraction is maintained at a near-normal level, and the threat of
      arrhythmias and sudden death is low. Levosimendan is the first calcium sensitizer
      to become available for the treatment of patients with acute heart failure. In
      recent clinical studies, levosimendan increased cardiac output and stroke volume
      without significantly increasing oxygen demand. By its additional action as a
      vasodilator (via potassium channel opening), levosimendan also corrects the
      hemodynamic decompensation, thus lowering the pulmonary capillary wedge pressure
      and systemic vascular resistance. Furthermore, levosimendan increases the
      coronary circulation thus leading to an improved function of the stunned
      myocardium and lessened ischemia. Taken together, levosimendan's primary calcium
      sensitizing action, along with its complementary vasodilator properties, make
      this new drug a highly promising agent for the treatment of patients with acute
      heart failure.

PMID- 14635368
TI  - Levosimendan in patients with low-output heart failure: lessons from the LIDO
      trial.
AB  - The novel calcium sensitizer levosimendan improves myocardial contractility
      without causing an increase in intracellular calcium and cyclic adenosine
      monophosphate concentrations. It also has a vasodilator action due to an opening
      of the adenosine triphosphate-sensitive potassium channels. In a double-blind
      clinical trial levosimendan was compared with dobutamine in 203 patients with
      severe low-output congestive heart failure. A 24-hour infusion of these inotropic
      drugs was administered to increase the cardiac output by at least 30% together
      with a decrease in the pulmonary capillary wedge pressure by > or = 25%. The pre
      defined hemodynamic improvement was achieved in 28% of patients receiving
      levosimendan compared to only 15% with dobutamine (p = 0.022). Levosimendan also
      reduced the 1- and 6-month mortality more than dobutamine (7.8 vs 17%, p = 0.045
      and 26 vs 38%, p = 0.029, respectively). Levosimendan produced less myocardial
      ischemia and cardiac arrhythmias than dobutamine. Calcium sensitizers offer a new
      therapeutic possibility in patients with decompensated low-output heart failure.

PMID- 14635369
TI  - Considerations on the efficacy and safety of levosimendan in ischemic heart
      failure.
AB  - Levosimendan is a new vasodilator agent with properties which improve cardiac
      contractility by calcium sensitization. Its dose-related efficacy and prolonged
      action have been documented in several major studies both against placebo and
      dobutamine. Out of 997 patients, 837 (84%) had acute or stable heart failure due
      to coronary heart disease. Therefore, it would be most interesting to analyze the
      efficacy and safety of levosimendan in heart failure due to ischemic heart
      disease. The dose-finding study included 98 patients who were given intravenous
      levosimendan at different doses and 20 patients treated with dobutamine. All
      patients had heart failure due to coronary heart disease. The other major trial
      included 500 acute myocardial infarction patients with heart failure and was
      placebo-controlled. In other levosimendan vs placebo or dobutamine comparative
      trials 50-60% of patients had ischemic heart disease and severe heart failure.
      Levosimendan significantly improves the cardiac index by 30-39% at bolus doses of
      6-24 micrograms/kg/min followed by infusion doses of 0.05-0.2 microgram/kg/min
      and reduces the wedge pressure by 20-25% to optimal levels (from 15-20 mmHg).
      There is a lesser blood pressure reduction and some heart rate increase. However
      in patients with an acute myocardial infarction the rate of ischemia or
      hypotension were similar in levosimendan- and placebo-treated patients and in the
      dobutamine controlled trials no major adverse effects were seen or they were more
      frequent in dobutamine patients. There is no increase in mortality either
      compared to placebo or to dobutamine. Rather, the opposite seems to be true. No
      increase in arrhythmias is seen. The hemodynamic effects of levosimendan are dose
      dependent and the current recommended doses are safe. No increase in mortality or
      any life-threatening arrhythmias have been observed.

PMID- 14635370
TI  - Preliminary clinical experience with the repetitive administration of
      levosimendan in patients with end-stage heart failure.
AB  - We present our preliminary clinical experience with the initial and repetitive
      administration of the novel inotropic agent levosimendan in a cohort of 20
      patients with end-stage heart failure who were acutely decompensated or whose
      symptoms were refractory to the usual pharmacological treatments thus
      necessitating hospitalization. Repetitive levosimendan infusions were
      administered to 9 patients (minimum 2, maximum 8 pulses). The effects of this
      therapy on the symptomatic status, vital signs, hemodynamic performance and
      clinical outcomes are discussed.

PMID- 14635371
TI  - The need for inotropic drugs in anesthesiology and intensive care.
AB  - The management of the failing heart represents an increasingly frequent challenge
      to both anesthesiologists and intensive care physicians, due to the increased
      prevalence of ventricular dysfunction in the population and to the ever-expanding
      indications for the surgical treatment of cardiac disease. Inotropic drugs are
      nowadays invaluable therapeutic tools in the treatment of perioperative heart
      failure and of the different forms of heart failure found in intensive care unit
      clinical practice. Postoperative myocardial dysfunction is a major concern in the
      setting of cardiac surgery since it is extremely frequent and is related to a
      greater morbidity and mortality. The different forms of heart failure, the
      rationale and the indications for the use of inotropic drugs in anesthesiology
      and intensive care are discussed in this review.

PMID- 14635372
TI  - The clinical experience with levosimendan in anesthesiology and in the intensive
      care unit.
AB  - In the present review striking data showing that intensive care unit patients
      with acute heart failure and high-risk surgical patients may markedly benefit
      from the use of levosimendan are presented. Indeed, levosimendan is an effective
      new agent that acts via two complementary mechanisms. It enhances cardiac
      contractility by improving the response of the myofilaments to intracellular
      calcium, and it reduces the cardiac workload by opening the adenosine
      triphosphate-dependent potassium channels for the dilation of blood vessels.
      Because the therapeutic levels of levosimendan do not increase the intracellular
      calcium concentrations, levosimendan is less likely than traditional inotropes
      (beta-agonist inotropes or phosphodiesterase inhibitors) to elicit arrhythmias or
      impair diastolic relaxation. In fact, the results of recent clinical studies
      indicate that levosimendan offers significant hemodynamic and survival benefits
      when given to patients who are hospitalized for acute heart failure. Indeed, in
      the near future, it is likely that levosimendan may also prove effective for the
      treatment of patients with diastolic heart failure or for those with a low
      cardiac output following coronary artery bypass grafting. In addition,
      levosimendan has the potential of supporting the cardiac function during the
      initiation of beta-blocker therapy, for weaning patients from cardiopulmonary
      bypass, for individuals with valvular abnormalities and for those with
      myocarditis. Preliminary results also suggest that levosimendan may be beneficial
      for the treatment of patients with right ventricular heart failure. Although the
      use of levosimendan has been fully validated for the most common causes of acute
      heart failure, additional clinical trials are needed to safety broaden its
      therapeutic indications.

PMID- 14635373
TI  - Neurological implications of hyperhomocysteinemia in patients with
      atherothrombotic disease.

PMID- 14635374
TI  - Risk stratification for arrhythmic events in patients with idiopathic dilated
      cardiomyopathy: a review of the literature and current perspectives.
AB  - The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) has
      markedly improved during the last decade, mainly because of advancements in
      therapeutic strategies. However, sudden death still accounts for a significant
      part of the total mortality in patients with moderate disease. Recent primary
      prophylactic trials failed to demonstrate any benefit of cardioverter
      defibrillator implantation in an unselected group of idiopathic DCM patients and
      thus the identification of the subgroup of patients at high arrhythmic risk is
      crucial. Although different risk stratification methods have been evaluated in
      risk assessment, the reported clinical value differs in studies, mainly because
      of differences in either methodology and/or patient selection. The present review
      focuses on arrhythmic events in idiopathic DCM and on the value of noninvasive
      methods and electrophysiological study in the risk stratification of this group
      of patients.

PMID- 14635375
TI  - Aortic valve dysfunction and dilated ascending aorta. A complex and controversial
      association.
AB  - Several pathogenetic mechanisms account for the association of the ascending
      aorta dilation with aortic valve dysfunction. Functional aortic insufficiency can
      derive from medial degeneration of the aortic wall and annuloaortic ectasia;
      leaflet structural disease can determine root dilation by increasing aortic wall
      stress in case of both regurgitation and stenosis; aortic valve disease and
      aortic aneurysm can however coexist due to two different intrinsic etiologies. In
      the attempt to best tailor the surgical correction of such conditions to the
      underlying causative mechanism, several technical options have already been
      developed including composite or separate aortic valve and root replacement,
      valve-sparing operations, and aortoplasty techniques. The criteria for surgical
      indication cannot leave the underlying pathogenesis out of consideration as well.
      The newly acquired knowledge in the basic research on this topic is expected to
      affect the approach to the individual patient in the future.

PMID- 14635376
TI  - The epidemiologic evolution and present perception of hypertrophic
      cardiomyopathy.
AB  - Patients with rare diseases are confronted by limited attention from the
      scientific community, a delayed diagnosis, a limited availability of resources
      and high costs of treatment. Although hypertrophic cardiomyopathy (HCM) does not
      meet the criteria for rare diseases, many physicians are uncomfortable with the
      disease, and patients still pay a price for the perceived "rarity" of HCM. In the
      year 2000, as part of a large research project on cardiovascular disease
      prevention (Progetto Cuore), the Italian Institute of Health has approved and
      funded a National Registry of HCM. The aims of the registry included: the
      collection of clinical data for HCM patients in different geographical areas; the
      creation of a network of cardiologists involved in the care of HCM patients; and
      an improved access of patients to the most advanced treatment options. It is our
      hope that the registry will be imitated by other countries, and that it will
      contribute to overcome the limitations of "rarity" in HCM research.

PMID- 14635377
TI  - The association between atrial septal aneurysm and mitral valve prolapse in
      patients with recent stroke and normal carotid arteries.
AB  - BACKGROUND: The association between mitral valve prolapse (MVP) and cryptogenic
      stroke is controversial. The Atrial Septal Aneurysm Multicenter Italian (ASA-MI)
      Study is a prospective multicenter study evaluating the prevalence of atrial
      septal aneurysm (ASA) in patients with a recent stroke and normal carotid
      arteries. The aim of the present research was to evaluate the frequency of ASA
      and its association with MVP in the stroke population and in the subgroup of
      young patients (< 55 years) included in the ASA-MI Study. METHODS: The study
      group included 245 of the 606 patients referred for transesophageal
      echocardiography (168 men and 77 women, mean age 65.7 +/- 21 years). All patients
      were selected on the basis of a recent episode of unexplained cerebral ischemia
      and were included in the study if they had normal carotid arteries. The control
      population included 245 patients (mean age 64.7 +/- 23 years) who underwent
      transesophageal echocardiographic evaluation during the same period for
      indications other than cerebral ischemia. The subgroup of young patients (< 55
      years) included 90 patients (61 men and 29 women, mean age 49 +/- 5 years).
      RESULTS: The prevalence of MVP was 18% (95% confidence interval 8 to 21%) in the
      stroke population and 15% (95% confidence interval 7 to 20%) in the control
      population (chi 2 = 2.1, p = NS). The prevalence of MVP did not differ between
      young stroke patients (28.8%) and young controls (20%) (chi 2 = 0.835, p = 0.3).
      MVP was not significantly associated with stroke. We found an association between
      ASA and MVP: there was a higher incidence of MVP in stroke patients with an ASA
      than in patients without stroke or an ASA (40.9 vs 25%, p < 0.05). There was also
      a higher frequency of MVP associated with ASA in the group of young patients than
      in all patients of the ASA-MI Study (28.8 vs 18%, chi 2 = 20.313, p < 0.001).
      CONCLUSIONS: We found an association between ASA and MVP in patients with recent
      stroke and this association bore a higher risk of cerebral events than in
      patients without these abnormalities.

PMID- 14635378
TI  - Intraventricular conduction defects in patients with congestive heart failure:
      left but not right bundle branch block is an independent predictor of prognosis.
      A report from the Italian Network on Congestive Heart Failure (IN-CHF database).
AB  - BACKGROUND: In industrialized countries the prevalence of congestive heart
      failure (CHF) is increasing. Many clinical factors have been shown to influence
      the prognosis of CHF. The effect of a wide QRS on mortality is debated; while
      left bundle branch block (LBBB) has been already identified as a negative
      prognostic factor, the effect of right bundle branch block (RBBB) is still
      unknown. The aim of this study was to compare the association of these two
      intraventricular conduction defects on the prognosis of CHF. METHODS: Data were
      derived from the Italian Registry of CHF. Entry in the Registry required that
      patients had a diagnosis of CHF based on the European Society of Cardiology
      guidelines. We analyzed the 1-year follow-up data of 5517 outpatients with CHF of
      different etiologies. The presence of a wide QRS was defined if the duration was
      > 120 ms. RESULTS: A wide QRS was present in 2066 patients (37.5%), 25.2% with
      LBBB, 6.1% with RBBB, 6.2% with other intraventricular defects. At univariate
      analysis patients with complete LBBB had a significantly higher 1-year mortality
      than those without (16.1 vs 11.9%) but this was not true for complete RBBB (11.9
      vs 11.9%). Even after multivariate adjustment, complete LBBB still remained an
      independent predictor of death (relative risk 1.36, 95% confidence interval 1.15
      1.61). CONCLUSIONS: LBBB but not RBBB is an independent predictor of death in
      CHF.

PMID- 14635379
TI  - Distal filter protection during percutaneous coronary intervention in native
      coronary arteries and saphenous vein grafts in patients with acute coronary
      syndromes.
AB  - BACKGROUND: Percutaneous coronary interventions on saphenous vein grafts (SVG)
      and in patients with acute coronary syndromes (ACS) have been associated with the
      distal embolization of the thrombus and plaque and to the no-reflow phenomenon.
      We report on the safety and feasibility of a new distal emboli protection filter.
      METHODS: Angioplasty using distal filter protection (Angioguard, Cordis, Warren,
      NJ, USA) was attempted in 38 patients (mean age 65 +/- 11 years, 79% males)
      affected by ACS. A percutaneous coronary intervention was performed in 27 native
      coronary arteries, in 10 SVG and in one arterial graft (mean diameter stenosis 88
      +/- 9%). Patients with vessels presenting severe proximal tortuosity, more than
      mild calcification, a diameter < 3.0 mm and a lesion length > 15 mm were
      excluded. RESULTS: It was possible to position the device in all patients (100%);
      in 7 patients (18%) the lesion could be crossed with the filter only after
      balloon predilation. Procedural success with final TIMI flow 3 was obtained in
      all patients and the mean residual diameter stenosis after stent implantation was
      5 +/- 8%. Transient procedural complications without clinical sequelae included
      the no-reflow phenomenon (2 patients, 5%) and vessel perforation (1 patient,
      2.5%). In no case was distal embolization observed. As regards the device-related
      complications, one occlusive dissection (2.5%) occurred and was successfully
      treated with stent implantation. In-hospital and 30-day major adverse cardiac
      events consisted of two non-Q wave myocardial infarctions (5%), both occurring
      during SVG interventions. CONCLUSIONS: The use of the Angioguard filter for
      preselected lesions in patients with ACS had a high technical success and carried
      a low rate of device-related complications. The clinical efficacy of the device
      needs further evaluation.

PMID- 14635380
TI  - The Kansas City Cardiomyopathy Questionnaire: Italian translation and validation.
AB  - BACKGROUND: Several studies have demonstrated that patients affected by heart
      failure have a compromised quality of life and, in the last few years, "health
      related quality of life" has become an important outcome indicator for the
      evaluation of heart failure treatment and a basis for the improvement of its
      strategies. METHODS: The translation into Italian of the Kansas City
      Cardiomyopathy Questionnaire (KCCQ), a new, 23 item, disease-specific health
      status instrument for patients with congestive heart failure, and its subsequent
      validation by asking 50 consecutive patients in our heart failure outpatient
      clinic to answer it. The KCCQ was compared to the "Minnesota Living with Heart
      Failure Questionnaire" (MLHF). RESULTS: The Italian version of the KCCQ
      correlates well with the MLHF for all domains with the exclusion of symptom
      stability score and MLHF emotional domain. However, the KCCQ, due to its multiple
      domains, provided more detailed information about the patients' status, and
      identified the more compromised ones. CONCLUSIONS: The KCCQ appears to be a valid
      and reliable instrument for the assessment of a patient's quality of life and the
      degree of limitations imposed upon him/her by the disease. When compared to the
      MLHF, the KCCQ, however, is somewhat more sensitive in identifying more
      compromised patients. This capacity could be advantageously used for the
      identification of clinical changes in future trials and lead to a better planning
      of new therapeutic interventions.

PMID- 14635381
TI  - In patients with coronary artery disease endothelial function is associated with
      plasma levels of C-reactive protein and is improved by optimal medical therapy.
AB  - BACKGROUND: Endothelial function is impaired in patients with coronary artery
      disease (CAD); in these patients plasma levels of C-reactive protein (CRP) and
      impaired endothelial function are related to future cardiac events. The aim of
      the present study was to evaluate the effects of medical therapy on endothelial
      function and CRP in patients with CAD. METHODS: Seventy-three patients (52 men,
      21 women, mean age 66 +/- 9 years) with CAD and 32 control subjects (25 men, 7
      women, mean age 65 +/- 11 years) were enrolled in the study. The endothelial
      function was evaluated by means of flow-mediated dilation (FMD) of the brachial
      artery following ischemia and CRP by means of a high-sensitivity assay. After
      baseline evaluation of CRP and FMD all patients received full medical therapy for
      3 months and were then again tested for endothelial function and CRP. RESULTS:
      Compared to healthy controls, patients had significantly more impaired
      endothelial function (FMD 3.6 +/- 3.2 vs 8 +/- 2.4%, p < 0.01) and higher CRP
      plasma levels (1.6 +/- 0.9 vs 0.9 +/- 0.56 mg/dl, p < 0.05). At baseline a
      significant negative correlation was found between CRP plasma levels and FMD in
      patients with CAD (r = -0.56, p < 0.05) while no correlation was found in
      controls. Medical therapy resulted in a significant improvement in endothelial
      function (3.64 +/- 3 vs 7.2 +/- 3.5%, p < 0.01), and a decrease of CRP (-0.26 +/-
      0.19, p < 0.01); the changes in CRP and FMD were independent of the drug used. A
      positive correlation was found between the improvement in FMD and the degree of
      CRP reduction (r = 0.57, p < 0.01). CONCLUSIONS: In patients with CAD plasma
      levels of CRP are associated with an impaired endothelial function suggesting a
      correlation between inflammation and the integrity of the endothelium. Full
      medical therapy reduces CRP with a parallel improvement in endothelial function.

PMID- 14635382
TI  - Echocardiographic diagnosis in diffusely aneurysmal coronary artery disease.
AB  - We present the case of a 73-year-old male with diffusely aneurysmal artery
      disease. Echocardiography revealed a 4.5 cm mass, adjacent to the right side of
      the heart, suggesting a diagnosis of coronary artery aneurysm. The findings were
      confirmed at magnetic resonance imaging and coronary angiography. Moreover, in
      view of the reported strong association between coronary and cerebral artery
      disease, the patient was submitted to cerebral magnetic resonance imaging, which
      also demonstrated aneurysmal disease involving the cerebral arteries.

PMID- 14635383
TI  - Silent acute myocardial infarction following a wasp sting.
AB  - Hymenoptera sting can lead to an acute myocardial infarction by different
      pathogenetic mechanisms depending on the presence of preexistent coronary
      atherosclerosis, the development of shock or the therapeutic use of epinephrine.
      The case of a 67-year-old man with acute myocardial infarction with ST-segment
      elevation after a wasp sting treated with fibrinolysis and without significant
      coronary atherosclerosis is reported. Of particular interest in the present case
      report is the silent presentation and the absence of any pharmacological
      interference. It follows that in any case of hymenoptera envenomation a standard
      ECG is advisable even when a clearly defined allergic reaction is not present.

PMID- 14635384
TI  - First successful bridge to recovery with the Impella Recover 100 left ventricular
      assist device for fulminant acute myocarditis.
AB  - A patient with septic and cardiogenic shock secondary to acute fulminant
      myocarditis was successfully treated by mechanical offloading of the left
      ventricle using the Impella Recover 100, a new implantable micro-axial blood pump
      designed for short-term circulatory support (for a maximum of 7 days). The
      possibility of implanting this device without using cardiopulmonary bypass
      allowed as to manage the septic shock, to reverse cardiac and hepatorenal failure
      and to wean the patient off treatment after 18 days of support. At 3 months the
      left and right ventricular function was satisfactory. The widespread application
      of this kind of support depends on the availability of an inexpensive "mini
      invasive" blood pump, appropriate weaning protocols and emerging strategies to
      promote sustainable myocardial recovery.

PMID- 14635385
TI  - Beta brachytherapy of an old degenerated saphenous vein graft with occlusive in
      stent restenosis.
AB  - We report a case of obstructive in-stent restenosis in a diffusely diseased
      saphenous vein graft complicated by a non-ST-elevation myocardial infarction.
      With tirofiban infusion, the extensively occluded saphenous bypass was
      reperfused, establishing a TIMI flow 3, and then entirely irradiated with a beta
      source (32P) without any complication. At 7 months the patient was asymptomatic
      and the control angiogram did not reveal any restenosis. In conclusion, 32P beta
      brachytherapy may be extremely effective not only in case of native vessel in
      stent restenosis but also in cases of high-risk vein graft in-stent restenosis.

PMID- 14635386
TI  - Images in cardiovascular medicine.  Membrane-type subaortic stenosis in the
      adult.

PMID- 14635387
TI  - [Psychological problems and cognitive impairments in the GUCH Community].
AB  - The increase of the GUCH Community requires a new definition of cardiac surgical
      success, which has to be considered either in terms of survival or quality of
      life and quality of health. Clinical and psychological problems are present in
      this population secondary to native cardiac disease, surgical correction, and
      social environment. Cognitive impairment after cardiac surgery is not rare, but
      an exhaustive evaluation of the psychological and neurodevelopmental outcome of
      patients operated on for total correction of congenital heart disease is complex
      and its clinical significance can be obtained by the integration of cardiological
      data, psychological status, and sociodemographic variables.

PMID- 14635388
TI  - [Significance of exercise capacity in cardiology].
AB  - Exercise capacity is reduced in many patients with cardiovascular disease. In
      post-acute myocardial infarction, ischemic heart disease and heart failure
      patients, exercise capacity has a strong independent prognostic impact. Even in
      subjects without history of heart disease, the lower the cardiorespiratory
      fitness the higher is the risk for cardiovascular events and mortality. With
      appropriate physical activity, exercise capacity is improved in most individuals.
      Improvement of functional capacity is associated with improvement of survival.

PMID- 14635389
TI  - [Prognostic evaluation in patients with heart failure].
AB  - The prevalence of heart failure has rapidly increased in the last decade and
      morbidity and mortality for this disease are high. Several predictors have a
      prognostic value in heart failure such as clinical, hemodynamic, functional,
      biochemical and electrophysiological patterns. The male sex, the old age and the
      etiology are known to be important clinical parameters and the left ventricular
      ejection fraction, the cardiac output and size and the pulmonary capillary wedge
      pressure represent important hemodynamic parameters. In recent years, exercise
      testing has been used for prognostic purposes and exercise capacity is an
      important component of the risk profile in heart failure by assessing the maximum
      oxygen consumption and the anaerobic threshold. Plasma levels of noradrenaline,
      renin, aldosterone and natriuretic peptides are related to the severity and
      prognosis of heart failure as well as heart rate variability, ventricular late
      potentials and T-wave alternans with regard to mortality due to arrhythmias.

PMID- 14635390
TI  - [Stunning, hibernation, and heart failure in patients with coronary disease:
      crucial role of impaired coronary flow reserve].
AB  - Hibernating myocardium can be defined as a chronic, but reversible left
      ventricular dysfunction that may contribute to congestive heart failure in
      patients with coronary artery disease. The dysfunction can improve after coronary
      revascularization and therefore its identification and treatment become central
      in the management of patients with heart failure secondary to coronary artery
      disease. Hibernating myocardium can be detected by several techniques
      (echocardiography performed during the infusion of dobutamine, single photon and
      positron emission tomography-PET, and magnetic resonance imaging), but none of
      these techniques can be considered unequivocally superior to the others for the
      identification of hibernating myocardium. As PET technology has advanced, the
      noninvasive quantification of absolute regional myocardial blood flow has become
      possible. The measurement of myocardial blood flow by PET has contributed to the
      demonstration that transmural blood flow in hibernating muscle is generally
      within the normal range while the coronary flow reserve is invariably and
      severely impaired. These findings have contributed to a new pathophysiological
      theory of hibernation where repetitive ischemia and stunning are considered as
      the initial mechanisms that might start the process of myocardial hibernation.

PMID- 14635391
TI  - [Epidemiology of acute coronary syndromes in cardiology departments of the Emilia
      Romagna region: the AI-CARE2 study].
AB  - BACKGROUND: The aim of this study was to better delineate the characteristics,
      treatments and outcomes of patients with acute coronary syndromes in Emilia
      Romagna, a region of Italy, with 4 million inhabitants. METHODS: From January 10
      to March 12, 2000, we performed a prospective survey (24/27 hospitals of the
      region) on 1074 consecutive patients with a discharge diagnosis of acute coronary
      syndrome. RESULTS: Based on the initial electrocardiogram, patients were
      classified as having an ST-elevation acute coronary syndrome in 41% of cases, a
      non-ST-elevation acute coronary syndrome in 54%, and an acute coronary syndrome
      with an undetermined electrocardiographic pattern in 5%. The discharge diagnosis
      was Q wave myocardial infarction in 43%, non-Q wave myocardial infarction in 26%,
      and unstable angina in 31% of patients. The use of antiplatelet, beta-blockers,
      ACE-inhibitors, and antithrombin agents for patients with ST-elevation acute
      coronary syndromes were 96, 62, 56, and 93%, respectively, with corresponding
      rates of 93, 63, 53, and 87% for non-ST-elevation acute coronary syndromes.
      During the initial admission, coronary angiography, percutaneous coronary
      intervention, and coronary bypass surgery were performed in 31, 15, and 1% of ST
      elevation acute coronary syndrome patients, respectively, with corresponding
      rates of 43, 15, and 5% for non-ST-elevation acute coronary syndromes. Among
      patients with ST-elevation acute coronary syndromes, 61% received a reperfusion
      treatment; 58% coronary thrombolysis, and 3% primary percutaneous coronary
      intervention. The in-hospital mortality of patients with ST-elevation acute
      coronary syndromes was 10%, of patients with non-ST-elevation acute coronary
      syndromes 3%, and of patients with underdetermined electrocardiographic acute
      coronary syndromes 8%. At 6 months, the mortality rate increased to 16, 8, and
      18%, respectively. CONCLUSIONS: Our data show the use of evidence-based
      pharmacological treatments in this population. This is associated with clinical
      outcomes which favorably compare with those observed in clinical trials. However,
      there is still room for improvement in the implementation of the invasive
      treatment.

PMID- 14635392
TI  - [Diagnostic and therapeutic features of pulmonary embolism in elderly patients].
AB  - BACKGROUND: Pulmonary embolism (PE) is often underdiagnosed in the elderly for
      nonspecificity and atypicity of presentation. The aim of this study was to
      evidence, retrospectively, the clinical, instrumental and laboratory aspects in
      the diagnosis of elderly patients with suspected PE and to observe the
      antithrombotic primary prophylaxis, acute antithrombotic treatment and its
      hemorrhagic side effects in patients with confirmed PE (CPE). METHODS: We
      conducted an observational, retrospective, study on 118 hospitalized patients >
      or = 65 years (49 males and 69 females, mean age 77.76 +/- 7.17 years) during a 5
      year period who underwent a scintigraphic lung scan for suspected PE. Clinical,
      instrumental and laboratory findings of 75 patients with CPE were compared with
      43 patients with unconfirmed PE (UCPE). RESULTS: Symptoms of dyspnea and chest
      pain and all the considered signs, except tachycardia, were significantly more
      frequent in the CPE group. Bed rest > 4 days, venous insufficiency, deep vein
      thrombosis, obesity and stroke were the risk factors significantly more frequent
      in the CPE group. Sinus tachycardia, incomplete right bundle branch block, ST-T
      alterations were significantly more present in the CPE group. Cardiomegaly was
      the only significant more frequent chest X-ray finding in the CPE group, while
      echocardiography showed a significant involvement of the right ventricle in the
      CPE group. Plasma D-dimer levels were significantly higher in the CPE group but
      the mean values were > 500 micrograms/l in both groups. In arterial blood gas
      analysis we found more severe hypoxemia, arterial hyposaturation and higher
      alveolar-oxygen gradient in the CPE group, while we did not find a more frequent
      respiratory alkalosis in this group. Heart failure, ischemic heart disease and
      chronic obstructive pulmonary disease were the more frequent diagnoses in the
      UCPE group. None of the patients received thrombolysis. Seventy percent of the
      CPE patients received intravenous heparin; 9 hemorrhagic side effects occurred, 3
      of them being major with one fatal in one patient treated with subcutaneous
      unfractionated heparin. CONCLUSIONS: Our study shows the diagnostic difficulties
      of PE in the elderly because of nonspecifcity of clinical, instrumental and
      laboratory aspects. Although many of these aspects are significantly more
      frequent in the CPE group, the same are often the main aspects also in the UCPE
      group. Moreover, our study reveals the low utilization of antithrombotic primary
      prophylaxis and high risk of hemorrhagic side effects of heparin in this subgroup
      of patients.

PMID- 14635394
TI  - [Systematic primary angioplasty in acute myocardial infarction: quality cannot be
      improvised].

PMID- 14635393
TI  - [Primary angioplasty in acute myocardial infarction: experience and results in
      the first 1,000 consecutive patients].
AB  - BACKGROUND: One of the biggest debates in modern cardiology regards the relative
      merit of primary percutaneous transluminal coronary angioplasty (PTCA) versus
      thrombolysis for the treatment of acute myocardial infarction with persistent ST
      segment elevation. After the excellent results with primary PTCA in trials and
      meta-analyses, the next question is whether such results might be duplicated in
      "real world" conditions. METHODS: Between January 1995 and April 2003, 1000
      consecutive patients with acute myocardial infarction, out of 2272 (44%) with ST
      segment elevation admitted to the coronary care unit at the Cardiology Department
      of the S. Anna Hospital, were treated with PTCA. Our Institution is a medium-high
      volume center, without on-site surgery. Usual clinical and interventional
      practice, adjunctive antithrombotic therapy and results are described in this
      paper. RESULTS: Primary PTCA has been performed in 825 patients (75%) out of 1095
      undergoing emergency angiography, "facilitated" in 140 (13%), rescue in 35
      (3.2%). Eighty patients of the "facilitated" PTCA group had been pre-treated with
      tissue-type plasminogen activator 50 mg i.v. bolus, 50 with abciximab and 10 with
      reduced doses of fibrinolytic and abciximab. One hundred and seventy patients
      (16%) had been transferred to our Institution from community hospitals. Nine
      patients out of 1000 undergoing PTCA (0.9%) have been transferred immediately
      after the procedure (bail-out, failure) to perform urgent coronary artery bypass
      grafting. PTCA has been completed by stenting in 919 patients (92%). The median
      door-to-balloon time was 58 min (25th-75th percentile 49-71). The in-hospital
      total mortality rate was 4.9% (49 deaths): 5.3% (44 deaths) in the primary PTCA
      group, 2.1% (3 deaths) in the "facilitated" PTCA group (p = 0.042), and 5.7% (2
      deaths) in the rescue PT-CA group. Early reinfarction rate was 1.5% (15 cases).
      The median time to hospital discharge was 10 days (25th-75th percentile 7-14).
      CONCLUSIONS: Since 9 years, our practice in the treatment of acute myocardial
      infarction with persistent ST-segment elevation is going on extending the use of
      primary PTCA, integrating pharmacological and mechanical options in selected
      cases.

PMID- 14635395
TI  - [Should we use clopidogrel instead of ticlopidine in elective coronary
      angioplasty?].
AB  - The use of ticlopidine in association with aspirin has reduced the incidence of
      subacute stent thrombosis to currently < 1% after coronary stent implantation.
      Clopidogrel, a more recently marketed thienopyridine derivative, has a lower
      incidence of side effects than ticlopidine. The use of clopidogrel in association
      with aspirin as compared to aspirin alone from the second through the sixth month
      after coronary angioplasty has been shown to reduce the 6-month incidence of
      major adverse cardiac events by 20-30%. Comparative studies about the use of
      ticlopidine and clopidogrel in patients undergoing stent implantation are scarce:
      these data are briefly reviewed. The conclusion is reached that, except for
      patients with non-ST-elevation acute coronary syndromes, there is at present no
      evidence that ticlopidine should be replaced with clopidogrel in all patients
      undergoing stent implantation; clopidogrel might be reserved for those patients
      who have shown side effects due to ticlopidine.

PMID- 14635396
TI  - [The AFFIRM study: is all that glitters gold?].

PMID- 14635397
TI  - [Is it time to organize a new battle against heart failure?].

PMID- 14635398
TI  - [Again about the clinical method: the beginnings a century ago].

PMID- 14635399
TI  - [Blockade of CD40/CD154 signal as a therapeutic strategy for autoimmune
      diseases].

PMID- 14635400
TI  - [Antiphospholipid antibody associated thrombocytopenia].

PMID- 14635401
TI  - [The pathogenesis of fibrosis in scleroderma].

PMID- 14635402
TI  - [Chronic active Epstein-Barr virus infection and related diseases].

PMID- 14635403
TI  - [A case of pseudoscleroderma as paraneoplastic syndrome due to carcinoma of
      cervical uteri].
AB  - A 65-year-old female began experiencing arthralgia, morning stiffness and
      psychroesthesia in April 2000. She visited a rheumatologist and was suspected of
      having early-stage rheumatoid arthritis. She was referred to our hospital, and
      was admitted in December 2000. At that time, sclerosis of the skin was advanced,
      and Raynaud's phenomenon was confirmed. The patient also exhibited nailfold
      bleeding, and was diagnosed as having systemic scleroderma. She visited a
      gynecologist for screening and cervical uteri carcinoma was confirmed. She
      underwent surgery in March 2001, and subsequently, sclerosis in her skin was
      almost stopped. We believe that these clinical symptoms were related to
      paraneoplastic syndrome. We therefore immunochemically investigated the
      pathogenesis of paraneoplastic syndrome and found that connective tissue growth
      factor (CTGF) might be involved and transforming growth factor-beta (TGF-beta)
      might not be involved in this case.

PMID- 14635404
TI  - [A case of Williams syndrome with p47-phox-deficient chronic granulomatous
      disease].
AB  - A 2-month-old boy with a characteristic elfin face was diagnosed as having
      Williams syndrome by means of specific fluorescence in situ hybridization (FISH)
      analysis for a chromosomal microdeletion located in 7q11.23. He was suspected to
      have immunodeficiency because of a persistent enlargement of axillary lymphnodes
      after immunization with Bacille Calmette-Guerin (BCG) vaccine since 7 month-old
      of age. The nitroblue tetrazolium test (NBT) and the chemiluminescence test
      revealed an absence of superoxide production. Western blotting and DNA sequence
      analysis confirmed the diagnosis of p47-phox-deficient autosomal recessive
      chronic granulomatous disease (CGD) (A47 degrees CGD). The predominant genetic
      defect in A47 degrees CGD was a GT deletion at the beginning of exon 2 in
      neutrophil cytosol factor 1 gene (NCF1) located in 7q11.23. It suggests that CGD
      in this patient resulted from the hemizygosity of recessive genetic mutation in
      NCF1 located at 7q11.23 associated with Williams syndrome. In such a disease with
      the chromosomal microdeletion like Williams syndrome, we should consider a
      combination with autosomal recessive diseases, the genes of which are located in
      the hemizygous region.

PMID- 14635406
TI  - Top compliance issues for first half of 2003.

PMID- 14635405
TI  - [Successful treatment of intravenous cyclophosphamide pulse therapy for systemic
      lupus erythematosus complicated with steroid-resistant hemolytic anemia].
AB  - (Case 1) A 13-years-old female had multiple arthralgia and butterfly rush, when
      she admitted in our hospital in May 2001. Nephropathy, hemolytic anemia (Hb 6.3
      g/dl and direct Coombs 3+) and high titers of antinuclear antibodies and anti-ds
      DNA antibody were disclosed and she was diagnosed as systemic lupus erythematosus
      (SLE). Although combination therapy of PSL 60 mg/day with a steroid pulse
      therapy, cyclosporine or an immunosorbent treatment, severe hemolytic anemia
      remained. However, monthly cyclophosphamide pulse therapy (IV-CY), which was
      started for the steroid-resistant hemolytic anemia, has gradually become
      effective and Hb improved up to 11.4 g/dl after 6 courses of IV-CY. (Case 2) A 53
      years-old woman diagnosed as SLE in 1978 and she had PSL 5 mg for over 10 years.
      Severe anemia (Hb 5.9 g/dl) was disclosed with a slight fever in June 2001, and
      she admitted in our hospital for further examinations. Progressive hemolytic
      anemia was revealed with marked decrease of Hb (3.4 g/dl) and high titer of
      direct Coombs (3+). Neither PSL (50 mg/day) nor steroid pulse therapy were
      effective against hemolytic anemia. In contrast, 3 courses of monthly IV-CY (500
      mg/day) resulted in the resolution of hemolysis. It is well known that the
      steroid-resistant hemolytic anemia is extremely hard to treat and leads to
      miserable prognosis, but we here propose IV-CY as an alternative and invaluable
      choice for the treatment of refractory hemolytic anemia complicated with SLE.

PMID- 14635407
TI  - Winners of the 2003 Eisenberg Patient Safety Awards.

PMID- 14635408
TI  - Network accreditation program redesigned.

PMID- 14635409
TI  - Shared visions--new pathways terms defined.

PMID- 14635410
TI  - [Are we going towards a neurological psychiatry?].

PMID- 14635411
TI  - [Right heart support during coronary artery bypass grafting without
      cardiopulmonary bypass].
AB  - BACKGROUND AND OBJECTIVES: Exposure of lateral and inferior coronary vessels
      during off-pump coronary artery bypass grafting may cause significant hemodynamic
      compromise due to right ventricular compression when tilting the heart. Some new
      right ventricular assistance devices have been developed in order to avoid this
      problem but only a few series have been published. A preliminary experience with
      a right heart circulatory support system is reported. METHODS: A total of eight
      patients underwent off-pump coronary artery bypass grafting using a right heart
      support device. Technical procedure and clinical outcome are analyzed. RESULTS:
      The right heart circulatory support device insertion and management were
      performed without any complication. A total of 21 distal coronary anastomoses
      were completed. They were located on the anterior descending artery(8),
      circumflex branches(6), diagonal branches(2), posterior descending artery(3) and
      right coronary artery(2). The right ventricular support device delivered flow at
      a medium rate of 2.2 L/min, providing hemodynamic stability when tilting the
      heart and exposing the coronary arteries. CONCLUSIONS: The use of right heart
      support devices is a simple and low risk procedure which may facilitate surgical
      anastomoses on lateral and inferior epicardial vessels during off-pump coronary
      artery surgery.

PMID- 14635412
TI  - [Utility of beta-blockers in the treatment of chronic heart failure].
AB  - Heart failure has become a major public health problem. About 2-3% of people over
      65 years suffer from Heart Failure. A huge amount of money is spent every year
      treating problems connected with this syndrome. In this paper we analyse
      randomised prospective trials which support the use of beta-blockers in these
      patients. We also analyse the benefits of this treatment and some special
      considerations concerning the use of these drugs.

PMID- 14635413
TI  - [Molecular biology of follicular thyroid carcinoma (II). Clinical applications].
AB  - The great advance of molecular medicine over the last few years gives us an
      attractive vision of the new possibilities in diagnosis and therapeutics of
      thyroid cancer and helps us to understand its biological behaviour. The clinical
      application of the growing understanding of gene alterations involved in
      thyroidal oncogenesis is becoming a reality. Such knowledge might contribute to
      greater diagnostic accuracy, by helping us characterise malignant or benign
      cells, predict tumour outcome or state its origin. Likewise it might be useful to
      know the response to conventional therapies or the future implications of
      pharmacogenetics. In addition molecular medicine applications ought to be
      considered in determining the prognosis of spontaneous and familiar carcinomas.
      Such information can significantly improve current clinical-pathologic prognostic
      methods.

PMID- 14635414
TI  - [Post-infarction left ventricular free wall rupture].
AB  - We report four cases of subacute left ventricular free wall rupture after
      myocardial infarction successfully treated with emergency surgery. Some aspects
      dealing with clinical presentation, diagnosis and treatment are discussed.

PMID- 14635415
TI  - [Large false aortic aneurysm after 30 years of a coarctation repair].
AB  - We report a case of a large false aortic aneurysm that had developed in a 43-year
      old man who had had coarctation repair 30 years previously. The coarctation
      repair had been done by inserting an end-to-end Dacron tubular graft which was
      sutured with silk. The re-operation was successfully performed under deep
      hypothermic arrest and it was noted that there was complete separation of the
      graft from both ends and no sutures were visualised. The deep hypothermic
      technique has considerably improved the ease and safety of this operation. We
      attribute this complication to the reabsorption of the silk sutures. Patients
      after coarctectomy with graft material should have regular chest X-rays for life
      in order to detect false aneurysms.

PMID- 14635416
TI  - [Medical ethics and Alzheimer patients].

PMID- 14635417
TI  - [Voriconazole].

PMID- 14635418
TI  - [Problem situations between health personnel and patients. Qualitative analysis
      of medical and psychological aspects of the complaints].
AB  - Paper deals with problems of patient's complaint about the activity of health
      care workers. Author submits his findings resulting from the qualitative analysis
      of individual cases, which are aimed at cases with medical and psychological
      aspects (namely in the communication). Exchange of information between the health
      care workers and patients belongs to the most risky situations from the point of
      complaint. As a conclusion, some preventive measures are recommended.

PMID- 14635419
TI  - [Fibrinolytic therapy in acute myocardial infarct].
AB  - Direct PTCA is a treatment of choice in patients with acute myocardial infarction
      with ST segment elevations (STEMI). Fibrinolysis remains important modality of
      treatment in these patients. Currently, there are more then 100 tissue
      plasminogen activator mutants available with different fibrin specificity. In a
      clinical practice, tissue-type plasminogen activator (t-PA), recombinant tissue
      type plasminogen activator (rt-PA), tenecteplase (TNK-tPA) and lanoteplase (n-PA)
      are most important examples. Fibrinolytic treatment in STEMI patients should be
      used in patients presenting in first 4 hours after beginning of chest pain, when
      it is sure, that direct PTCA cannot be started within next 90 minutes.
      Concomittant therapy of acute STEMI patients consists of anticoagulans,
      antiplatelet and antiagregatory treatment.

PMID- 14635420
TI  - [Cardiogenic shock--a complex therapeutic approach].
AB  - Cardiogenic shock belongs to the most severe and immediately life-threatening
      complications of the acute myocardial infarction. Despite development of modern
      diagnostic and therapeutic methods the incidence and mortality of cardiogenic
      shock has not significantly declined in the past decades. Early reperfusion
      strategy with percutaneous revascularization has become a cornerstone of therapy.
      The complex approach to cardiogenic shock comprises pharmacological and
      mechanical hemodynamic support, ventilatory support utilizing new ventilator
      regimens, metabolic and renal support/replacement with continuous renal
      replacement therapies and psychological, eventually psychopharmacological
      support. All these measures enable prevention of the multiple organ failure
      syndrome development and positively influence high mortality of patients
      suffering from cardiogenic shock.

PMID- 14635421
TI  - [New views on immunopathology of viral hepatitis B and C].
AB  - The interaction of non-cythopatic, hepatotropic viruses of hepatitis B and C with
      the host's immune system plays a critical role in determining the viral clearance
      and it contributes to the liver damage. The initial line of defence is antigen
      non-specific and is mediated by natural killer cells and macrophages.
      Simultaneously, virus-specific immunity is induced by professional antigen
      presenting cells that process and present viral antigens to T and B lymphocytes
      in the regional lymph nodes. Thereafter, viral specific T helper cells are
      activated and these cells initiate the anti-viral immune responses of B and CTL
      lymphocytes. Early, multispecific T cell responses are associated with viral
      clearance, whereas the imbalance of viral specific Th1 and Th2 lymphocytes plays
      a crucial role in the viral persistence. The imbalance of viral specific Th1 and
      Th2 lymphocytes leads to inadequate activation of antigen specific CTL cells.
      After recognition of viral antigens, T helper lymphocytes are differentiated to
      Th1 and Th2 cells according to the type of secreted cytokines. Th1 cells produce
      cytokines: interleukin-2, IFN-gamma, TNF-alpha, which are responsible for
      effective activation of CTL cells. In contrast, interleukin-4, interleukin-5 and
      interleukin-10 are secreted by Th2 cells, which are involved in activation of B
      lymphocytes and in production of neutralizing antibodies. These finding suggests
      that the viral clearance is associated with the early development and adequate
      mounting of the anti-viral multispecific immune responses of T helper and
      cytotoxic T lymphocytes.

PMID- 14635422
TI  - [Cellular and tissue hypoxia--role of the von Hippel Lindau gene and hypoxia
      inducible factor-1].
AB  - Hypoxia results in increased expression of some genes. This can compensate
      effects of hypoxia on the organism, and adapt cells and tissues to the
      environment with low oxygen tension. Mechanisms of cell and tissue responses to
      hypoxia have been extensively studied last years. The first identified mediator
      of cell response to hypoxia was hypoxia-inducible factor (HIF-1), which is being
      up regulated during hypoxic conditions. It binds to regulatory regions of
      sensitive genes and increases their transcription rate. Other key elements of
      cell response to hypoxia have been described recently--von Hippel-Lindau protein
      and prolyl hydroxylases, that allow degradation of alpha-subunit of HIF-1 during
      normal oxygen tension. This can ensure low level of HIF-1 in cells under
      physiological oxygen tension thus the expression of target genes is maintained on
      basal level. These new findings are starting points for further research and
      possible therapeutic use.

PMID- 14635424
TI  - [Transhepatic cholangioscopy in the treatment of choledocholithiasis].
AB  - Endoscopic methods gained the leading position in the treatment of
      choledocholithiasis. Transhepatic cholangioscopy and contact lithotripsy is used,
      if standards methods (ERC) are not successful. The transhepatic approach is
      predominantly used for the therapy of complicated choledocholithiasis.
      Cholangioscopy and lithotripsy can be performed after PTC, external drainage of
      bile ducts and dilatation of intrahepatic channel. The success rate for
      transhepatic methods is 90 to 100%, the major complication rate is 5 to 7.5%.

PMID- 14635423
TI  - [Psychosocial factors associated with genetic testing for certain hereditary
      types of neoplasms].
AB  - Mutations in predisposing genes for some of the hereditary forms of cancer
      exhibit autosomal dominant mode of inheritance. Introduction of genetic tests for
      these mutations to the clinical practice initiated studies focused on the
      psychosocial factors associated with genetic testing. Undergoing the genetic
      testing is a stressful experience for both the healthy individuals in risk and
      the patients already affected with cancer. The psychosocial characteristics of
      the tested individual influence not only the psychological functioning during the
      testing but also the acceptance of the test, and generally his life style and
      health practices. Psychological support during the genetic testing process is
      mostly provided by the genetic counsellor. The findings of psychosocial studies
      might be therefore helpful for the focusing of the genetic consultation, and
      fulfilling the client needs and expectations towards testing. Factors of
      motivation, psychological state, influence of family situation and support, and
      optionally the involvement of a psychologist into the process of genetic testing
      are observed.

PMID- 14635425
TI  - [Bone metabolism in individuals dependent on heroin and after methadone
      administration].
AB  - BACKGROUND: The aim of the work was to determine how the prolonged opioid
      addiction influence bone metabolism. In heroin addicts and after one year of
      methadone maintenance we investigated bone mineral density, biochemical markers
      of bone metabolism and serum levels of testosterone. METHODS AND RESULTS: The
      study involved 37 persons, 31 men and 6 women in average age of 26 years
      (variation 18 to 39 years). Values of type I collagen cross-linked telopeptide,
      osteocalcin, propeptide of type I collagen and testosterone in serum were
      measured by radioimmunoassy and immunoanalysis. Bone mineral density was measured
      by dual energy absorptiometry. Body Mass Index was calculated. In heroin addicts
      at the femoral neck and in distal forearm osteopenia was found. After one year of
      methadone maintenance treatment the bone density remained unchanged.
      Concentrations of osteoresorption marker (type I collagen cross-linked
      telopeptide) and osteoformation markers (osteocalcin and propeptide of type I
      collagen) were in heroin addicts in comparison with control group significantly
      increased (averages 814 ng/l, 43.1 mu/l, 76.4 mu/l). Testosterone level in serum
      in addicted men was significantly decreased (3.3 nmol/l). After one year of
      methadone maintenance treatment biochemical markers of bone metabolism restored
      when compared with the control group, testosterone levels remained unchanged.
      Statistical measurements were performed by t-test and paired t-test. CONCLUSIONS:
      Prolonged heroin addiction is associated with accelerated bone turnover and
      osteopenia in cortical bone without evidence of metabolic bone disease. Methadone
      maintenance treatment restores altered bone turnover only. One possible
      explanation of high bone turnover in heroin addicts may be the influence of
      hypopituitary-hypothalamo-gonadal axis. However, it may not be the only mechanism
      involved.

PMID- 14635426
TI  - [Methods of determination of the number of CTG/CAG repeats in trinucleotide
      repeats in the human genome].
AB  - BACKGROUND: Human genome dynamic mutations are a new class of gene mutations
      represented by an unstable number of trinucleotide repeats and causing severe
      human hereditary neuromuscular and neurodegenerative diseases. The identification
      of pathological expanded alleles on the molecular level is important for clinical
      diagnostics. METHODS AND RESULTS: For the molecular diagnostics of expanded
      tandem repeat trinucleotide sequences we have introduced a fast and efficient TP
      PCR fluorescent method according to Warner et al. (1996). We have modified this
      TP-PCR method for a rapid detection of expanded CTG alleles of the DMPK gene
      (myotonic dystrophy, MD) into a two-level protocol; first, the heterozygote
      sample DNAs were selected using P1/P2 primers flanking repeat tracts and, second,
      the TP-PCR protocol used was focused above all on the identification of a
      pathological allele. A fluorescent-labelled specific primer in TP-PCR was used
      for the exact determination of the number of CAG repeats of the gene IT-15
      (Huntington's disease--HD) in the diagnostically important region of the grey
      zone (35 to 39 CAG). The reproducibility of the PCR results was demonstrated on
      control DNA samples with the known genotype and, in the case of MD, also by
      Southern blot analysis. We have especially shown the possibility of a cheaper PCR
      P1/P2 and TP-PCR protocol, which can be used, with silver staining of separated
      PCR products on polyacrylamide gels. CONCLUSIONS: Our experience with introducing
      the above-mentioned PCR methods into laboratory practice clearly documents the
      possibilities of their general applicability in the molecular diagnostics of
      hereditary diseases characterised by instability of the trinucleotide repeat
      tracts.

PMID- 14635427
TI  - [Laboratory indicators of endothelial involvement in rheumatic diseases
      associated with vasculitis in children].
AB  - BACKGROUND: Endothelial activation is an important etiopathogenetic factor in a
      group of disorders characterised by primary or secondary vasculitis. The aim of
      our study was to determine blood concentrations of von Willebrand factor (vWF),
      vypusteno soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E
      sel) in children with various rheumatic diseases and in paediatric controls and
      to correlate them with clinical and laboratory variables. METHODS AND RESULTS:
      Total of 28 healthy children (ZD) and 48 patients were evaluated: 6 with systemic
      lupus erythematosus (SLE), 7 with other diffuse connective tissue diseases (SSD),
      11 with Henoch-Schonlein purpura (HSP), 14 with oligoarticular juvenile
      idiopathic arthritis (JIA) and 10 febrile controls (FC). Erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP) and full blood count were
      recorded. ICAM-1, E-sel and vWF concentrations were measured by sandwich ELISA
      kits. In SLE patients' concentrations of vWF and ICAM-1 were significantly higher
      than in healthy (p < 0.05), but not febrile controls. ICAM-1 was significantly
      increased also in SSD group when compared to healthy children (p < 0.01).
      Differences in other groups did not reach statistical significance. Significant
      negative correlation with age was observed for the group as a whole, E-sel
      correlated with leukocyte and thrombocyte counts (p < 0.01), both molecules with
      CRP (p < 0.05) and with each other (p < 0.01). CONCLUSIONS: Combined measurement
      of vWF, ICAM-1 and E-sel as possible markers of endothelial activation in such
      vypusteno wide spectrum of paediatric patients and controls is unique vypusteno.
      Our finding of increased concentrations of vWF and/or ICAM-1 in children with
      systemic autoimmune diseases underlines the importance of endothelial involvement
      in these disorders, but their predictive value in the disease monitoring needs to
      be further studied.

PMID- 14635428
TI  - [Viability of parathyroid gland tissue measured by flow cytometry].
AB  - BACKGROUND: Postoperative hypoparathyroidism after the total parathyroidectomy
      (PTX) remains a problem, no matter our experiences with 243 operations on
      parathyroid glands (PG). Implantation of "fresh" tissue, cryopreservation and
      reimplantation of cryopreserved tissue are performed with uncertain results. The
      aim of this project was to compare viability of cryopreserved tissue of
      parathyroid glands with "fresh" tissue obtained during parathyreoidectomy and
      with tissue from cadaverous donors. METHODS AND RESULTS: Group 1 included 55
      cryopreserved samples obtained from 41 patients after PTX (22M, 19F, a mean age
      of 46 +/- 11 years). Average duration of storage in liquid nitrogen was 84 +/- 49
      months. Group 2 included "fresh" tissue of PG, harvested during PTX. Viability
      was measured in different time in samples from 42 patients with
      hyperparathyroidism (11M, 31F, a mean age of 55 +/- 13 years). Group 3 included
      tissue of 14 cadaverous donors obtained during multiorgan harvesting (7M, 7F, a
      mean age of 31 +/- 5 years, WIT 32 min). Viability was measured by flow cytometry
      with propidium iodide after dissociation of tissue. Evaluation of PG tissue was
      proven by histology. Average viability in group 1 was 36.9 +/- 24.7%, no
      correlation with the duration of storage in liquid nitrogen was found. Average
      viability in group 2 was 51.4 +/- 24%. Viability in group 3 was 66.8 +/- 32%.
      Group 1 vs. group 2 were different with p < 0.05, group 2 vs. 3 did not reach
      significance (with marginal p = 0.06) and group 1 vs 3 were different with p <
      0.001. CONCLUSIONS: The highest viability was found in tissue of cadaverous
      donors, the lowest in cryopreserved tissue (with no correlation to the duration
      of storage in liquid nitrogen).

PMID- 14635429
TI  - [Clinical epidemiology--diagnosis].
AB  - Basic procedure for any clinician is to establish the diagnosis. There are some
      basic measures of diagnostic tests validity, which clinician should know and use
      for selection of appropriate diagnostic test and for the correct evaluation of
      test results. Sensitivity, specificity, positive and negative predictive values
      and likelihood ratio belong among those measures.

PMID- 14635430
TI  - [Protective care of children in the Czech Republic and the Convention on
      Children's Rights].
AB  - Protective Care of Children is one of the oldest activities aimed at the defence
      and maintenance of life. It represents a set of actions, activities, and
      interventions directed to every child, attempting to provide sufficient defence
      against unfavourable effects on its existence and development. It includes also
      the knowledge how to prevent them. At the same time attention of workers engaged
      in the children care is aimed at problems and their solution of developing
      impairments, disabilities and abnormalities of individual children and the whole
      child population. It requires an ability to recognize and eliminate endogenous,
      exogenous or combined adverse effects causing impairments of the children's life.
      It means treatment and rehabilitation to recover the positive state. The most
      important role in all such affords have parents and the family. To estimate the
      level and characteristics of children preventive care in CR, the first (1997) and
      second (2003) report on evaluation of the Committee on the Rights of the Child
      and the implementation of the Convention on the Rights of the Child was used. The
      first evaluation concerned mainly the general problems of children; the second
      evaluation was focused on individual groups of children in special circumstances.
      As most important, the Committee found excellent level of health and educational
      care (though in the second evaluation it found some imperfections in education),
      the foundation of telephone Childline line for consultation of children in stress
      and preparation of several laws concerning the family and children. In both
      evaluations the Committee repeatedly reproached imperfections in the
      implementation of the most important principles of Covention--the best interest
      in children, no discrimination, respects to the children's opinion, the right of
      parents to have children and vice versa, problem of institutionalization. Next
      problems reproached concerned the not having founded the Coordination organ for
      the complex protection of child, not having formulated the National plan of care
      for the family and child, not having solved problem of monitoring, research and
      education in that field. Though the reproaches of the Committee on the Rights of
      the Child to our protection of child are not insignificant, the overall view of
      the Committee and the discussion to the First and Second evaluation are possible
      to interpret as satisfactory. At the same time, they invite to it next improving,
      namely considering the basic reproaches and recommendations of the UN Committee
      on the Rights of the Child.

PMID- 14635432
TI  - Predictors of suspension and negative school outcomes: a longitudinal
      investigation.
AB  - Research suggests that suspension is not an effective deterrent and that more
      should be done to meet the needs of those who are continually suspended.

PMID- 14635431
TI  - Defining and redirecting a school-to-prison pipeline.
AB  - The school-to-prison pipeline needs to be better defined and redirected toward
      greater opportunities for all youth.

PMID- 14635433
TI  - Connected in Seattle? An exploratory study of student perceptions of discipline
      and attachments to teachers.
AB  - How do students' perceptions about their treatment in school differ along racial
      and gender lines?

PMID- 14635434
TI  - Punishing dangerousness through preventive detention: illustrating the
      institutional link between school and prison.
AB  - Evidence-based observations of how the juvenile justice and educational systems
      can work together more effectively are presented.

PMID- 14635435
TI  - High-poverty secondary schools and the juvenile justice system: how neither helps
      the other and how that could change.
AB  - Evidence-based observations of how the juvenile justice and educational systems
      can work more effectively together are presented.

PMID- 14635436
TI  - Deconstructing the pipeline: using efficacy, effectiveness, and cost-benefit data
      to reduce minority youth incarceration.
AB  - Investing in effective prevention and early intervention programs will reduce
      human costs of victimization and also save tax dollars in the short and long
      terms.

PMID- 14635437
TI  - NICE puts curb on use of ECT.

PMID- 14635438
TI  - Disability commission seeks law reforms.

PMID- 14635439
TI  - Users say bi-polar drugs are 'the worst ever'.

PMID- 14635440
TI  - Take your seats.

PMID- 14635441
TI  - Madness at the movies.

PMID- 14635442
TI  - A woman's space.

PMID- 14635443
TI  - Getting it right.

PMID- 14635444
TI  - The chance to move on.

PMID- 14635445
TI  - Anna suggested I read psalm 43 and said her fiance was coming any day to collect
      her for the wedding.

PMID- 14635446
TI  - On every page was the painstakingly printed and repeated statement, 'Had painted
      toenails.'.

PMID- 14635447
TI  - Lonely at the top.

PMID- 14635448
TI  - Your body tells the truth.

PMID- 14635449
TI  - Running my own life.

PMID- 14635450
TI  - A foot on the ladder.

PMID- 14635451
TI  - The elephant in the room.

PMID- 14635452
TI  - Diatribe.

PMID- 14635453
TI  - This life.

PMID- 14635454
TI  - Medical malpractice liability: no easy solutions.

PMID- 14635455
TI  - Austrian cases on medical liability.

PMID- 14635456
TI  - Medical civil liability in Belgium. Four selected cases.

PMID- 14635457
TI  - Medical malpractice in England--current trends.

PMID- 14635458
TI  - Medical malpractice liability in Spain: cases, trends and developments.

PMID- 14635459
TI  - The use of harmful to others-criterion for involuntary treatment in Finland.
AB  - During the past decades the Western countries have paid attention to their Mental
      Health legislation, in particular, by making changes concerning involuntary
      treatment. In Western countries legislation allows involuntary treatment of the
      mentally ill. Involuntary psychiatric treatment is motivated by either potential
      harm to others (for the good of society) or by need for treatment and/or
      potential self-harm (for the good of the patient). The aims of this study were to
      describe to what extent the danger to others criterion is used as a motivation
      for involuntary hospitalization and detainment in Finland, and to what kind of
      patients this criterion is applied. The study involves a retrospective chart
      review of all the treatment periods of a six month admission sample in three
      Finnish university hospitals. We found that potential harm to others has been
      rarely used as a motivation for involuntary referral or detainment together with
      other motivations, and virtually never as the sole motivation. With the exception
      of gender, which was most often male, patients with potential harm to others did
      not differ significantly from other involuntarily treated patients. Coercion
      (defined as seclusion, the use of restraints, forced medication, physical
      restraint or restrictions in leaving the ward) was not used with these patients
      more regularly than with the patients motivated by the other criteria. Length of
      stay (LOS) in a psychiatric hospital did not differ between the patients
      determined harmful to others and the other involuntarily treated patients.

PMID- 14635460
TI  - The legal and ethical aspects of medical malpractice in Turkey.
AB  - The issue of patients' rights is relatively unknown in our country but it is
      often recalled when an incident of death or disability is suspected as being
      caused by a physician's error. However patients' rights are being violated
      thousands of times every day in our country. More than these patients' rights'
      violations, the essential point is the lack of a mechanism to claim those rights
      and to complain about the practices which violate them. In our country, patients
      and their relatives are uninformed, powerless and unprotected against physicians
      and health organizations, and they typically accept whatever happens to them
      without complaint. Some of the reasons for this are, presumably, an
      underdeveloped consciousness of patients' rights, an absence of patient
      organizations, and insufficient ethical and legal regulations on patients'
      rights. These deficiencies were diminished somewhat by the "Regulation on
      Patients' Rights," which was prepared by the Ministry of Health in 1998. Another
      legal draft law referred to as "Responsibilities Due to Malpractice in Medical
      Services" has been prepared and is in the process of becoming law. This draft law
      and the general conditions of the country on this subject are evaluated in this
      article.

PMID- 14635461
TI  - Court of justice of the European communities.

PMID- 14635462
TI  - Double-blind, placebo-controlled study with sublingual immunotherapy in children
      with seasonal allergic rhinitis to grass pollen.
AB  - Sublingual immunotherapy (SLIT) has been recognized as a viable alternative to
      subcutaneous immunotherapy for respiratory allergies both in adults and children,
      but clinical documentation about safety and efficacy in children is still poor.
      The purpose of this study was to assess the efficacy and tolerance of SLIT in
      children who are sensitized to grass pollen. METHODS: Children with a clinical
      history of intermittent rhinoconjunctivitis, with or without mild asthma and
      positive skin prick tests to grass pollen, were selected to participate in a 2
      year double-blind, placebo-controlled study with SLIT, using a grass extract (ALK
      Abello). RESULTS: 22 children were analyzed at the end of the study. No relevant
      side effects occurred in the active group. A statistically significant difference
      (p = 0.05; Mann-Whitney test) in favor of the active group (n = 10) could be
      shown for drug consumption during the second year, as well as a significant
      improvement as compared to the first year of SLIT (p = 0.05; Wilcoxon test).
      CONCLUSIONS: Despite the small number of patients, our data suggest that SLIT
      with a grass pollen extract is well tolerated in children and is able to
      significantly reduce drug consumption during the second year of treatment.
      Studies in larger groups of children sensitized to both grass and tree pollens
      are needed to definitively assess the role of SLIT in intermittent, seasonal
      rhinitis and pollen asthma.

PMID- 14635463
TI  - The hazards of kissing when you are food allergic. A survey on the occurrence of
      kiss-induced allergic reactions among 1139 patients with self-reported food
      hypersensitivity.
AB  - BACKGROUND: According to a few case reports, kissing can induce symptoms due to
      food allergy. OBJECTIVE: We wanted to investigate the occurrence of kiss-induced
      allergic symptoms and other social inconveniences among patients with self
      reported food hypersensitivity. METHODS: A questionnaire was answered by 1139
      patients (1-84 years old, mean age 29 years, 393 males and 746 females) who
      considered themselves to be food allergic. RESULTS: 12% of the patients
      experienced allergic symptoms when in close contact with (e.g., kissing) a person
      who had eaten a nontolerated food prior to the contact. Some case histories
      suggested that the symptoms only appeared if the food intake had occurred
      immediately before the kiss. In addition, the questionnaires showed that 55% had
      problems in daily life finding tolerable food, 44% were afraid of a severe
      reaction from eating nontolerated food, 13% could experience symptoms when
      sitting beside a person who was eating such a food, and 17% could experience
      symptoms in the kitchen when someone else was preparing such food. CONCLUSIONS:
      What other people eat can influence the quality of life of food-allergic
      patients.

PMID- 14635464
TI  - Occupational asthma from natural rubber latex. Specific inhalation challenge test
      and evolution.
AB  - BACKGROUND: Natural rubber latex (NRL) is the most frequent cause of occupational
      respiratory problems in hospital workers. OBJECTIVE: To describe the diagnostic
      methodology, including the specific inhalation challenge (SIC), used on patients
      diagnosed as having occupational asthma due to NRL in our Allergy Department
      during a 6-year period from 1989 to 1995. METHODS: In 19 patients diagnosed as
      having occupational asthma due to NRL, clinical severity was assessed with a
      combined score for symptoms and medication use. Skin prick tests with
      aeroallergens, latex, papain, kiwi and chestnut, total IgE, serum-specific latex
      IgE, respiratory function study, methacholine test, specific conjunctival test,
      and SIC test with latex were done. RESULTS: All but three patients worked in
      hospitals. All presented urticaria and rhinoconjunctivitis, and six also suffered
      anaphylaxis, usually preceded by asthma. Clinical fruit allergy was present in
      eight patients. The latency period was variable (0.25-27 years). The intensity of
      symptoms was low to moderate. Specific IgE, skin prick, and conjunctival tests to
      latex were positive in all cases. SICs were done in 12 patients. All of them
      presented isolated immediate reactions. No adverse reactions were observed.
      Duration of follow-up ranged from 1 to 7 years. Twenty-six percent of the
      patients kept their job, 26% changed jobs but remained in health care, and 48%
      switched to jobs unrelated to health care. Only 16% were free of symptoms without
      treatment, while 32% needed bronchodilators and 52% needed inhaled steroids. The
      specific bronchial challenge test was safe, but it did not predict the course of
      the illness. Duration of exposure and intensity of symptoms did correlate with
      prognosis, however. CONCLUSIONS: NRL acts as a common aerollergen. Minor symptoms
      often precede occupational asthma. The SIC test was safe in the hands of trained
      technicians. Occupational asthma due to NRL seems to have a poor prognosis.

PMID- 14635465
TI  - Analgesic intolerance with or without bronchial asthma: is there a marker?
AB  - BACKGROUND: The prevalence of analgesic intolerance (AI) is less than 1% in the
      general population and about 10% in adult asthmatics, in whom the disease tends
      to be more severe. OBJECTIVE: A possible clinical-laboratory marker was sought
      that would differentiate patients who have AI with/without asthma, AI with
      asthma, and AI without asthma from the healthy subjects. METHODS: In the survey,
      66 analgesic-intolerant patients (36 having asthma) were compared with 50 healthy
      subjects using a nickel patch-test, 65 patients (39 having asthma) with 55
      healthy subjects for the presence of a genetic marker (A38G and A444C SNPs in
      CC16 and LTC4S genes), and 32 patients (14 having asthma) with 118 healthy
      subjects for presence and frequency of human leukocyte antigens (HLA). RESULTS:
      The mean age of the patients with AI with/without asthma and the healthy subjects
      for the nickel patch-test group, genetic marker group, and the HLA group was 39.8
      +/- 10.5 and 33.3 +/- 11.1, 41.5 +/- 11.6 and 38.1 +/- 13.4, and 39.4 +/- 12.5
      and 41 +/- 2.6, respectively. The frequency of the females in the same groups, in
      the same order, was 72.7% and 54%, 81.5% and 62%, and 71.9% and 59.3%,
      respectively. The frequency of positive nickel patch-test results and the A38G
      and A444C frequency in CC16 and LTC4S genes were not significantly different (p >
      0.05). The frequency of HLA antigens HLA-A3, -B52, -DR16, -DQ5, -DQ8 and -DQ9
      were significantly higher; and -A24, -B35, -B44, -DQ6 and -DQ7 were significantly
      lower in the AI group with/without asthma compared to the control group (p <
      0.05). CONCLUSION: As a result, nickel patch-test positivity and the genes which
      we have studied do not seem to be markers for AI with/without asthma. However,
      there might be a relation between AI with/without asthma and the types of the HLA
      system. Further surveys are needed with other genes and possible markers.

PMID- 14635466
TI  - Variation of the skin end-point in patients treated with sublingual specific
      immunotherapy.
AB  - The reduction in skin reactivity in sensitized subjects is a common finding after
      injective specific immunotherapy. Few data are, on the contrary, available for
      sublingual immunotherapy. We assessed the skin reactivity by the end-point
      titration method in 90 monosensitized subjects (age range 3-50; mean age 19.63)
      at the baseline and for four consecutive years during the SLIT treatment with two
      different maintenance regimens. The yearly duration of drug intake was monitored
      throughout the observation period. Age and skin reactivity to histamine (p <
      0.0001; r = 0.871), and age and skin prick end-point (p < 0.0001; r = 0.523)
      turned out to be statistically positively correlated at baseline. No correlation
      was on the contrary found between age and the ratio allergen wheal/histamine
      wheal (p = 0.857; r = -0.019). After 4 years all patients showed at least a
      significant 4-fold decrease of the skin end-point, whereas 46/90 (51.1%) showed a
      16-fold decrease and 29/90 (32.2%) a 64-fold decrease (p < 0.001 in all cases).
      At the end of the SLIT treatment, 21/90 patients (23.3%) were not using any drug,
      whereas 16/16 (100%) had given up the use of eye drops, and 34/35 (97%) had given
      up the use of bronchodilators and bronchial steroids (p < 0.001). After SLIT,
      52/90 patients showed a reduction by at least 50% of the yearly duration of drug
      intake (p < 0.0001). An apparent relationship between the progressively
      decreasing rate of use of drugs and the decrease in skin reactivity was found,
      but it did not reach the point of statistical significance (p = 0.081). Patients
      treated with the daily allergen administration schedule, in spite of a lower
      cumulative dosage, showed a significantly greater decrease in skin reactivity (p
      < 0.001) and a higher rate of both no use of any drug (p = 0.013) and of at least
      a 50% reduction of the yearly duration of drug intake (p = 0.001) as compared to
      patients treated with three allergen administrations per week.

PMID- 14635467
TI  - Immediate adverse reactions to immunotherapy.
AB  - BACKGROUND: Immunotherapy, which has been used since the beginning of this
      century, has potential adverse reactions. The purpose of this study was to
      evaluate immediate local and systemic reactions to allergen immunotherapy and to
      compare rates of adverse reactions to aluminum-adsorbed versus calcium-adsorbed
      allergen vaccines. METHODS: 108 cases (38 girls and 70 boys) were given allergen
      immunotherapy between 1997 and 2001. The following data were recorded for each
      patient: primary disease being treated (allergic rhinitis, asthma, or allergic
      rhinitis and asthma), allergic sensitivities (dust mite or grass pollen), number
      of injections, the stage of immunotherapy (buildup or maintenance), dilution of
      allergen vaccine, and type of allergen vaccine (calcium- or aluminum-adsorbed).
      Adverse reactions were classified as systemic or local. Local reactions were
      classified as hyperemia and induration less than 5 cm, more than 5 cm, itching,
      and pain. RESULTS: 4783 injections were evaluated in 108 subjects with allergic
      rhinitis (44%), asthma (40%), allergic asthma, and rhinitis (16%). Frequency of
      immediate systemic reaction was 0.13%. Frequency of immediate local reactions
      were: hyperemia and induration less than 5 cm 3%, greater than 5 cm 0.16%, local
      itching 0.15%, and local pain 0.2%. There was no significant difference in
      systemic and local reactions between calcium- and aluminum-adsorbed vaccines.
      Immediate local reactions were more frequent during maintenance therapy compared
      to buildup. Subjects were more likely to have local reactions during maintenance
      therapy if they had allergic rhinitis (p < 0.05) or were receiving grass pollen
      vaccine (p < 0.01). CONCLUSION: Immediate adverse reactions were uncommon when
      given to children with asthma and allergic rhinitis. Aluminium- and calcium
      adsorbed allergen vaccines showed similar rates of systemic and local reactions.

PMID- 14635468
TI  - Defective Fc-, CR1- and CR3-mediated monocyte phagocytosis and chemotaxis in
      common variable immunodeficiency and X-linked agammaglobulinemia patients.
AB  - Blood monocyte phagocytic functions were evaluated by chemotaxis, phagocytosis,
      and superoxide anion production in nine patients with common variable
      immunodeficiency (CVI), eight patients with X-linked agammaglobulinemia (XLA),
      and in 17 normal subjects. Further laboratory diagnosis included the
      determination of the Bruton's tyrosine kinase (Btk) protein expression in
      monocytes using flow cytometry. The analysis of monocyte phagocytic function
      demonstrated that CR3-, CR1-, and Fc-mediated phagocytosis (p = 0.0001) were
      significantly decreased in CVI and XLA patients, and chemotaxis of monocytes (p =
      0.0082) was reduced in XLA patients. Superoxide anion production, however, did
      not differ between the CVI, XLA, and the control groups. The cytoplasmic
      expression of Btk protein in monocytes was normal in CVI patients and decreased
      or not detected in XLA patients. It is proposed that impaired chemotaxis and
      phagocytosis by monocytes may be a characteristic of the innate immune system in
      CVI and XLA patients, providing a new direction for the physiopathology of these
      immunodeficiencies.

PMID- 14635470
TI  - The optimal immunotherapy cluster schedule in clinical practice.
AB  - The efficacy of injective immunotherapy is no longer a matter of debate, but
      concerns about its safety and compliance problems (because of the number of
      visits required for the build-up phase) are limiting factors for wider usage.
      Different schedules have, therefore, been used in clinical trials with the aim of
      improving both safety and compliance. We investigated the effects on tolerance of
      modifications to the starting allergenic dose, of the pharmaceutical presentation
      of the allergen (aqueous or depot), of the change of the number and volume of the
      daily administrations through progressive adjustments of the so-called clustered
      schedule. We took the rate of local and/or systemic side effects as the primary
      criterion, and were able to gradually reduce the rate of systemic reactions per
      dose and per patient from 4.1% and 65% to 0.3% and 2.6%, respectively, through
      four progressive modifications of the starting schedule. According to our data,
      it is possible to reach the maintenance dose in only four visits with 2
      administrations per visit. This was achieved either by switching from aqueous to
      depot extracts or by using depot extracts from the beginning. These results have
      been obtained without any kind of premedication and with a wide range of
      allergens, including mites, epithelia, pollens, and honeybee venom. We have shown
      that the number of injections administered following the conventional schedule
      could be reduced by 75%, shortening the build-up phase by 38.5%, without
      increasing the rate of side effects. We think clustered schedules could lead to a
      better compliance and to a broader use of injective immunotherapy.

PMID- 14635469
TI  - The bronchodilatory effects of loratadine, terbutaline, and both together versus
      placebo in childhood asthma.
AB  - AIM: To assess the bronchodilatory effect of loratadine in children with mild-to
      moderate asthma and to determine whether loratadine interacts with terbutaline.
      METHODS: The effect on pulmonary functions of a 10 mg oral dose of loratadine,
      with and without inhaled terbutaline powder (0.5 mg), was determined in 13
      patients with a mean (SE) age of 10.63 (0.77) years (range from eight to 17
      years) at 11 time points during 8 h in a randomized, double-blind, placebo
      controlled, crossover study. Forced expiratory volume in 1 s (FEV1) was the
      primary measure of efficacy. RESULTS: Although loratadine alone produced an
      increase in FEV1 relative to baseline, this was not statistically significant (p
      > 0.05). Terbutaline with, and without loratadine, significantly increased FEV1
      from 1 to 5 h according to baseline (p < 0.004). When compared with the placebo,
      loratadine significantly increased FEV1 from 150 min to 8 h (p < 0.05). Also,
      terbutaline alone, or in combination with loratadine, significantly increased
      FEV1 from 30 min to 7 h (p < 0.004, from 30 min to 5 h; p < 0.05, between 6-7 h).
      Although the mean increase in FEV1, with terbutaline + loratadine in combination,
      was greater than with terbutaline alone, the difference was not significant (p >
      0.05). CONCLUSION: Loratadine has a mild bronchodilatory effect in the study
      period and does not interfere with the bronchodilatory effect of terbutaline in
      childhood asthma.

PMID- 14635471
TI  - Comparison of skin tests to aeroallergens in Ankara and Seoul.
AB  - BACKGROUND: The environment contains many allergenic proteins, and skin test
      reactivity to aeroallergens may be different among people living in different
      regions. OBJECTIVE: To compare skin test results of Turkish and Korean patients
      with respiratory allergies. METHODS: The charts of 304 (160 male, 144 female)
      patients from Ankara, Turkey, and 208 (111 male, 97 female) patients' charts from
      Seoul, Korea, who had undergone skin prick tests were reviewed. Skin tests were
      classified as positive when the allergen-induced wheal size was the same size or
      larger than that caused by histamine. RESULTS: Grass pollens were found to be
      major allergens more often in Ankara than in Seoul (74.34% vs. 15.87%, p <
      0.001). Skin test reactivities in Ankara were significantly lower (p < 0.001)
      than in Seoul to weed (6.91% vs. 37.50%) and tree pollens (4.61% vs. 39.42%).
      Allergic reactions to indoor allergens were significantly higher (p < 0.001) in
      Seoul than in Ankara: house dust mites (HDM) (83.17% vs. 32.90%), cockroaches
      (45.67% vs. 1.97%), and cats (17.79% vs. 1.65%). CONCLUSION: Due to the different
      aeroallergen environment, the positive skin test results were different in both
      cities: grass pollens were the most common allergens in Ankara, while patients
      from Seoul reacted more commonly to indoor allergens, especially to HDMs and
      cockroaches.

PMID- 14635472
TI  - Catastrophic antiphospholipid-antibody syndrome and danazol.
AB  - We report a case of catastrophic antiphospholipid-antibody syndrome, with renal
      and neurological manifestations, which presented shortly after the institution of
      danazol for the treatment of refractory thrombocytopenia.

PMID- 14635473
TI  - Grape anaphylaxis.
AB  - Grape allergy is particularly rare in spite of the vast extension of Vitis
      vinifera cultivation on all continents. We report on the case of a 28-year-old
      woman who presented with allergic systemic reaction after eating white grapes
      (Vitis vinifera). She complained of two severe episodes of anaphylaxis after
      eating grapes, with generalized pruritus, acute generalized urticaria, facial
      swelling, lip and oropharingeal angioedema, and dysphagia. Both the episodes were
      treated at the Emergency Room level, with parenteral administration of
      corticosteroids and antihistamines. Skin prick tests with commercial extract of
      grapes provided a negative result, while prick by prick procedure performed with
      white grapes and white grape juice yielded a positive result. Grape-specific
      serum IgE were also detected. We conclude that in the diagnosis of grape allergy
      the currently available commercial extracts might not be completely reliable and
      the prick-by-prick procedure with fresh grapes should always be performed.

PMID- 14635474
TI  - Occupational rhinoconjunctivitis from white pepper.
AB  - A 44-year-old subject developed rhinoconjunctivitis symptoms when she was exposed
      to white pepper while working in the food industry. A positive skin prick test
      for white and black pepper extracts (1:10 w/v) were obtained. Specific IgE
      antibodies to white and black pepper were demonstrated by ELISA. The immunoblot
      analysis showed two IgE-reactive protein bands able to bind to IgE from white
      pepper extract of 11.8 kDa and 13.6 kDa and one band from black pepper extract of
      11.8 kDa. IgE binding to blotted white and black pepper extract were inhibited by
      preincubation of patient serum with black pepper extract. A conjunctival
      provocation test was positive with a white pepper extract dilution of 1:100 w/v.
      We describe a patient with occupational rhinoconjunctivitis caused by
      hypersensitivity to white pepper.

PMID- 14635475
TI  - Hidden fish substance triggers allergy.
AB  - Food allergy (hypersensitivity) is a form of adverse food reaction caused by an
      immunological response to a particular food. IgE-mediated food allergy is
      responsible for most immediate-type food-induced hypersensitivity reactions. The
      prevalence of food allergy in the general population, not including oral allergy
      syndrome, is about 1-2%. While adults might tend to be allergic to fish,
      crustaceans, peanuts, and tree nuts, children, on the other hand, tend to be
      allergic to cow's milk, egg white, wheat, and soy. Food is the most common
      eliciting factor of anaphylaxis (45%), followed by drugs (29%), and insect stings
      (21%). Our study describes a 3 1/2-year-old boy who is allergic to fish consumed
      via ingestion and inhalation. This case is a good example of how easily people
      with food allergies can unintentionally consume foods to which they allergic, and
      is a clear demonstration of the dangers of such effects.

PMID- 14635476
TI  - [Miguel Servet and pulmonary blood circulation].

PMID- 14635477
TI  - [Left superior vena cava and anomalies associated with it].
AB  - In order to assess the frequency of persistent left superior vena cava as well as
      the associated congenital heart disease, 66 hearts were studied from 1277
      necropsies of the pathologic collection of the Instituto Nacional de Cardiologia
      "Ignacio Chavez". They were analyzed with the sequential segmental approach. It
      was determined: atrial situs types and modes of atrioventricular and ventricular
      arterial connections, morphology of the superior systemic venous return and
      associated cardiopathies. 33 hearts had situs solitus (group I) and 34 hearts had
      isomeric situs (Group II) (30 with dextroisomerism and 4 with levoisomerism). The
      group I showed double superior vena cava, the left one had continuation with the
      sinus coronary; in 25 of them the left brachiocephalic vein was absent, in 6 this
      vein was present, 5 with narrow lumen and in one it was dilated (specimen with
      atresia of the Tebesian valve). The more frequent congenital heart disease were
      ventricular septal defects, troncoconal cardiopathies and anomalies in the
      atrioventricular connection. The hearts of group II did not have coronary sinus;
      the venous connections were in the atrial roof. 19 hearts had double superior
      vena cava and 15 specimens had only the left one. The congenital heart disease in
      this group were complex with multiple patterns of association. Left superior vena
      cava is developed as a consequence of persistence of the continuation of the left
      anterior and left common cardinal veins with the left horn of sinus venosus when
      the proximal segment of these veins did not disappear. The left superior vena
      cava has surgical significance when congenital heart disease is present.

PMID- 14635478
TI  - Transcatheter closure of secundum atrial septal defects and fenestrated Fontan
      using the Amplatzer septal occluder. Initial prospective study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of transcatheter closure of
      secundum atrial septal defects and fenestrated Fontan with the Amplatzer septal
      occluder. METHODS: Fifteen consecutive patients, with a significant interatrial
      communications, were considered for the procedure; four patients with defects
      that were too large or with deficient margins were excluded after initial
      transesophageal echocardiography. RESULTS: Eleven procedures were performed in 11
      patients (10 atrial septal defects and 1 fenestrated Fontan) aged 9 to 38 years,
      mean 17.7 +/- 9 years; body weight 30 to 87 kg, mean 51.4 +/- 16. The stretched
      balloon diameter of the defects ranged from 8 to 28 mm, mean 18.8 +/- 6.9; the
      diameter of the devices ranged from 10 to 30 mm, mean 20.8 +/- 6. Immediate total
      occlusion rate was 18.1%, rising to 63.6% after 24 hours. Total occlusion rate at
      one month reached 100%. Severe transient sinus bradycardia in one (9%) was the
      only complications. At follow-up (10 to 26 months, mean 13.2 +/- 5.0) all
      patients remain asymptomatic with no residual shunt. CONCLUSIONS: The Amplatzer
      septal occluder is very efficient and offered interventional interatrial
      communications closure in 100% of our group of consecutive patients with
      excellent intermediate results.

PMID- 14635479
TI  - [Balloon pulmonary valvuloplasty, 15-year experience at the Siglo XXI IMSS
      National Medical Center].
AB  - OBJECTIVE: To evaluate 15 years of experience with balloon pulmonary
      valvuloplasty in a single third level health care center. MATERIAL AND METHODS:
      Hundred-fifty patients underwent the procedure, 73 (48%) men and 77 (52%) women,
      mean age 10.5 +/- 11.3 years. RESULTS: The initial systolic gradient decreased
      from 86 +/- 35 to 21.67 +/- 12.20 mm Hg, p < 0.001, whereas the initial right
      ventricular systolic pressure decreased from 106 +/- 34.8 to 53 +/- 27 mm Hg, p <
      0.0001. At the end of the follow-up, 48 +/- 44 months, the systolic gradient was
      13.43 +/- 8.73 mm Hg, p < 0.001. Major complications occurred in 9 (6.4%)
      patients. Immediate technical success was achieved in 111 (74%) patients and
      failure in 39 (26%). At the end of the follow-up period, successful outcomes were
      achieved in 104 (89.6%); in contrast, failures were present in 12 (10.4%)
      patients, p < 0.001. Death occurred in 2 (1.33%) patients. The predictors for
      failure were age < 1.5 +/- 1-33 years (p < 0.004), dysplastic valve (p < 0.001),
      high initial systolic gradient (p < 0.002), and high initial systolic right
      ventricular pressure (p < 0.0001). CONCLUSION: Balloon pulmonary valvuloplasty is
      an effective, safe, and first choice treatment for congenital pulmonary valve
      stenosis.

PMID- 14635480
TI  - [Risk profile and survival in patients with heart failure caused by systolic
      function. Prospective study with 4-year follow-up].
AB  - BACKGROUND: Our current knowledge on the prognosis of systolic left ventricular
      dysfunction has been obtained through multicentric trials performed at third
      level health care institutions, which usually include patients based on strict
      inclusion criteria. OBJECTIVE: To establish in systolic left ventricular
      dysfunction patients, evaluated at a community hospital, a risk profile for
      adverse cardiovascular events and to know their survival. METHODS: Prospective
      study with 4 years follow-up. INCLUSION CRITERIA: a) Symptomatic patients with
      systolic left ventricular dysfunction, b) any NYHA functional class or etiology,
      c) ejection fraction < 40%. EXCLUSION CRITERIA: a) Asymptomatic patients, b)
      acute coronary syndrome in the last 6 weeks, c) ventricular dysfunction secondary
      to pulmonary arterial hypertension, d) severe systemic illness or neoplasms
      causing disability < 6 months. STATISTICS: Student's test, Chi-square, Yates and
      Mantel-Haenszel. Unvariant and multivariant logistic regression analysis. Cox and
      Kaplan-Meier method. Significance was set at p < 0.05. RESULTS: From January 1997
      to January 2001, 110 patients were studied, 61% men and 39% women, their age were
      61 +/- 13.1 years. Ischemic etiology in 46% and 54%, 68% in III/IV NYHA class and
      32% in I/II NYHA class. Basal left ventricular ejection fraction was 28 +/- 6.9%.
      Patients were followed for 30.11 +/- 18.7 months, with 26% of global mortality.
      Through lineal, logistic and multivariate regression analysis, the high clinical
      risk profile was identified, corresponding > 65 years, female gender,
      hypertension, diabetes mellitus II, ischemic heart disease, III/IV NYHA class and
      ventricular tachycardia (p = 0.00001). CONCLUSION: In the "real world" of
      systolic left ventricular dysfunction, the identified risk profile allows
      stratify high priority subgroup of patients to be enrolled in a cardiac
      transplant program.

PMID- 14635481
TI  - [Right coronary artery fistula opening into right ventricle. Echocardiographic
      findings and interventional management. Report of a case].
AB  - Coronary artery fistula is a rare condition in which a communication exists
      between a coronary artery an a cardiac chamber or systemic vein. It causes an
      obligatory shunt from the high-pressure coronary artery to a lower-pressure
      cardiac chamber. We report a case of right coronary artery fistula draining into
      the right ventricle, echocardiographic features and interventional
      catheterization.

PMID- 14635482
TI  - [Infrequent electrocardiographic changes during exercise stress test in a patient
      with Brugada's syndrome].
AB  - 38 year old patient with a syncope history and family background of sudden death
      had an electrocardiogram compatible with the "Brugada Syndrome". When an exercise
      stress testing with Bruce protocol was done, we found that during the effort
      phase and at maximum effort, contrary to a ST segment normalization, a discreet
      increase of the ST segment elevation of 2 mm in V1 and V2 occurred. During
      recovery phase a decrease in the ST segment elevation was observed, at a normal
      level as before the test.

PMID- 14635483
TI  - [Changes in heart metabolism and their possible usefulness in therapy (Part I)].
AB  - We describe different metabolic states of the heart, during developmental stages,
      hypoxia and illness, to understand and use them to try to reestablish the normal
      conditions.

PMID- 14635485
TI  - Heart failure clinics improve patient care, bottom line.

PMID- 14635484
TI  - [Images in cardiology. Endothelial dynamics in aortic root dissection. Study with
      three-dimensional echocardiography].

PMID- 14635486
TI  - John Casey's Medcath may be tough to beat.

PMID- 14635487
TI  - Solucient: $10 billion could be saved if all providers as good as top 100.

PMID- 14635488
TI  - Bay Area Medical Center wins back community's trust, business.

PMID- 14635489
TI  - USPI partners its way to success with leading not-for-profits.

PMID- 14635490
TI  - [Prosthetic evaluation of the sagittal curve of the edentulous mandibular ridge].
AB  - The literature lacks reports on measurement-based investigations of the sagittal
      curve of the mandibular ridge. The prosthetic significance of that curve is a
      debated issue even today. Our investigations have been carried out on functional
      samples of randomly selected edentulous patients (55 females and 17 males)
      treated at the Department of Prosthodontics of the Semmelweis University,
      Budapest. We made photographs using a Polaroid MACRO 5 SLR camera on a squared
      factory-made film, under standard circumstances, from both right and left
      directions. The photographs were then scanned with 600 dpi resolution and saved
      as non-compressed tif files (Tag Image File Format). The evaluation of the
      digitalized photographs has been carried out using a specifically developed
      computer program. On the four-times enlarged pictures, we made three measurements
      at each point; the arithmetical means of those sets of three figures served as a
      basis for statistical analysis. The data were analysed by gender and by side,
      using the SPSS program package (t-test). Our measurements showed that the
      sagittal curve is characteristic of the edentulous mandibular ridge as well.
      However, it does not exhibit significant differences by gender, individual, or
      side. The average value of the lowest point of the sagittal curve was 5.78 mm, s
      +/- 1.96 mm, minimum = 1.83 mm, maximum = 11.12 mm. It was concluded from our
      measurements and comparative anatomical data--clinical observations, as well as
      measurement-based investigations--that the Spee-curve of the healthy dentition
      and the sagittal curve of the edentulous mandibular ridge are formed by the same
      forces. If, in everyday practice, sagittal curves of the occlusion surfaces of
      complete lower dentures are set parallel with the mandibular edge, this is the
      most preferable solution with respect to both the stability of complete lower
      dentures and the optimal functioning of constrictor muscles.

PMID- 14635491
TI  - [Stomato-oncological screening in diabetic patients].
AB  - The data of the literature suggest that studies have not been performed to date
      on possible correlations between diabetes and precancerous states and tumors in
      the oral cavity. Internationally, only one investigation appears to have dealt
      with the incidence of leukoplakia among diabetics. In the present work, stomato
      oncological screening was performed on 200 treated diabetics. Precancerous
      lesions were found in 8%, and benign lesions in 14.5%. Comparison with earlier
      Hungarian screening studies indicated that benign and precancerous lesions occur
      with greater frequency among diabetics than in the average population. The
      proportion of oral cavity lesions is higher among diabetics of type 2 than among
      those of type 1. The combination of diabetes mellitus and smoking means an
      enhanced risk from the aspect of precancerosis of the oral cavity.

PMID- 14635492
TI  - [SIMS (secondary ion mass spectroscopy) and XPS (x-ray photoelectron
      spectroscopy) study of titanium implant surfaces coated with anodic titanium
      oxide layer].
AB  - The demands that must be satisfied by titanium implants applied in medical
      practice include chemical and physical durability. An anodic oxide protective
      layer formed on the surface of titanium implants serves for the better attainment
      of this aim. The composition of the passivizing layer and the changes in its
      thickness and binding state can be studied by method of material science, e.g. by
      secondary ion mass spectroscopy (SIMS) and X-ray photoelectron spectroscopy
      (XPS). In this way a possibility arises for the material technological
      classification of the Ti-TiO2 layer structure and for the observation of the
      physical and chemical reactions that occur between the implants and the tissues
      in the organism. The present XPS examinations revealed that the binding state of
      the titanium forming the surface of the plates involve neither significant
      quantities of titanium oxide nor impurities. In the SIMS investigation the
      thickness of the titanium oxide layer was found to be 120-150 nm. Determination
      of the thickness of the surface, the binding state of the titanium and the exact
      proportions of the impurities and additives furnishes a possibility for a
      subsequent comparison with the surface structure of plates removed from the
      organism. It is important for the assessment of the practical value of the
      protective layer.

PMID- 14635493
TI  - [Effectiveness of standardized direct suggestions in dental hypnosis].
AB  - The frequency of occurrence of amnesia, analgesia and time distortion during
      hypnotic dental treatments (n = 60) was investigated on high dental anxiety
      patients. Hypnosis with and without standardised direct suggestions related to
      amnesia, analgesia and time distortion were compared. Treatment of alert patients
      without direct suggestions (n = 10) were also used for comparison. Amnesia and
      time distortion was higher (p < or = 0.05) with the use of suggestions under
      hypnotic conditions, but analgesia was not significantly different. Alert
      appearance of the events were in all cases less (p < or = 0.01) than under
      hypnotic conditions.

PMID- 14635494
TI  - [Glass fiber polymerization--an effective method of increasing fracture
      resistance of the denture base (case reports)].
AB  - Three cases are presented to demonstrate how the application of glass fibres
      could be integrated into the treatment plan of removable dentures. In Case one
      the lack of space excluded the use of chrome-cobalt framework, but glass fibre
      reinforcement for the implant prothesis, secured by ball attachments, ensured
      structural stability. In Case two in order to keep the upper canine, an
      overdenture was constructed, which incorporated glass fibres in its dental base
      to prevent fracture propagation there. In Case three where the transfer of an
      extremely great chewing load to the dental base caused repeated fractures, the
      complex treatment of second framed work, fibres reinforcement and reline gave a
      stable satisfactory result over a long-term monitoring period. It was concluded,
      as presented, that the application of glass fibre reinforcement polymerised in
      the denture base can ensure structural stability and prevent fracture.

PMID- 14635495
TI  - [Effects of photo-acoustic stimulation combined with hypnotherapy on saliva
      secretion. A pilot study].
AB  - Effect of photo-acoustic stimulation on the flow rate and protein concentration
      of whole saliva was investigated. 10 medical students' and 11 edentulous
      patients' salivary volume and protein concentrations were measured before,
      during, and after stimulation. The flow rate of the students' group was
      significantly higher (p < or = 0.01) before and after the treatment, whereas the
      protein concentration was significantly lower (p < or = 0.05) before, during and
      after treatment comparing to the patients' group. The flow rate of the students'
      groups significantly decreased during stimulation (p < or = 0.05). Salivary
      protein concentration of the students' group significantly increased (p < or =
      0.05) after stimulation. There were no significant changes in the group of
      patients. Repeated stimulation combined with hypnotic relaxation was used in the
      case of 4 psychosomatic patients. Resting salivary flow and protein concentration
      significantly increased in 2 cases (p < or = 0.05) as a result of the therapy.

PMID- 14635496
TI  - Mesothelioma as marker of both exposures and effects.

PMID- 14635497
TI  - Factors affecting growth of FEV1.
AB  - There is an increasing awareness that also growth in FEV1 may be of importance to
      development of chronic obstructive lung disease in later life. This paper reviews
      current knowledge on factors in foetal and childhood life that may reduce lung
      growth. Passive smoking as well as malnutrition in foetal life is related to
      impaired lung function in later life. Birth weight is a risk factor to lung
      growth independent of gestational age and maternal smoking. Active and passive
      smoking in childhood and adolescence reduces growth. Girls seem to be more
      vulnerable than boys to the effect of smoking. Also host characteristics like
      atopy, bronchial hyper responsiveness and asthma are related to impaired growth
      of FEV1. Lower respiratory tract infections before the age of seven are also
      related to impaired lung growth in adult life. Although several studies have
      found socioeconomic status among adults related to chronic obstructive lung
      disease, it is not known to what extent low socioeconomic status affects growth
      of lung function after adjusting for risk factors like active and passive smoking
      and lower respiratory tract infections. Normal lung growth varies with age and
      between male and female. The importance of the various risk factors may differ
      depending at what point in the lung growth they come into play. Limited data is
      available about the interrelationship between the risk factors and the mechanisms
      through which they work.

PMID- 14635498
TI  - Lung protective ventilation in ARDS: role of mediators, PEEP and surfactant.
AB  - Lung protective ventilation such as the ARDSnet low tidal volumes strategy can
      reduce mortality in ARDS patients. The knowledge that an essential therapy such
      as mechanical ventilation on the intensive care influences patient outcome has
      given rise to the re-evaluation of current ventilation practices. This review
      addresses the current state of lung protective strategies and their physiological
      rationale. Latest knowledge on the instigation and progression of lung injury by
      mechanical ventilation is explored, particularly the interaction between
      ventilation and the inflammatory response occurring in an ARDS lung. Furthermore,
      the role of tidal volume, PEEP, recruitment manoeuvres and surfactant on lung
      injury is discussed. Finally, we discuss results from clinical studies on
      mechanical ventilation and elucidate these results with data acquired in
      experimental studies. Guidelines for future strategies and/or investigations are
      presented.

PMID- 14635499
TI  - Hospital monitoring, setting and training for home non invasive ventilation.
AB  - Although in recent years guidelines have been published in order to define
      indications, applications and delivery of long-term home non invasive mechanical
      ventilation (HNMV), there is lack of information with regards to in-hospital
      assessment, planning and training to initiate and prescribe it. Discontinuation
      and lack of compliance versus HNMV may affect the follow-up of these patients
      adding a costly burden for care. The present review proposes an operative flow
      chart for optimisation of HNMV prescription from initial patient's selection to
      post discharge follow up including; 1. assessment of the correct choice of
      ventilator, interfaces, ventilation setting. 2. Timing for different
      physiological monitoring (arterial gases, mechanics, sleep) 3. Timing for
      clinical evaluation, machine adaptation, carer training and long term follow-up.

PMID- 14635500
TI  - Use of bronchodilators during non-invasive mechanical ventilation.
AB  - Bronchodilators represent one of the most important therapeutic weapons for the
      treatment of airway obstructive diseases and the inhaled route of administration
      is very often employed due to the greater drug availability and reduced magnitude
      of side effects. During acute exhacerbations, it is not unfrequent that the
      elastic and resistive loads imposed on the ventilatory pump overcome the force
      sustainable by the respiratory muscles and the patient requires ventilatory
      assistance, in order to relieve fatigue and to optimize alveolar gas exchange.
      During these episodes, inhaled bronchodilators, far from being discontinued,
      sometime must be administered during mechanical ventilation, that, in hypercapnic
      ventilatory failure can be frequently applied noninvasively with a good rate of
      success. While in the current literature there are a lot of data about inhaled
      drug administration during invasive mechanical ventilation, very few data are
      available on the topic of aerosol therapy during noninvasive mechanical
      ventilation. With the present paper we want to analyze the rationale, the
      feasibility and the current data dealing with the administration of inhaled drugs
      during noninvasive mechanical ventilation.

PMID- 14635501
TI  - The role of prophylactic brain irradiation in small cell lung cancer treatment.
AB  - AIM: To review the effectiveness and safety of prophylactic cranial irradiation
      (PCI) in patients with small-cell lung cancer (SCLC). RESULTS: Brain metastases
      are frequent in SCLC with a cumulative incidence of 25% among 1,202 in 17 trials,
      and a 3-5 months median survival from first occurrence. The 5-year cumulative
      rate of brain metastases as isolated first site of relapse was 37% among 260
      patients without PCI compared to 20% among 245 with PCI in two randomised trials
      (p < 0.001). A meta-analysis on seven randomised trials of PCI versus no PCI
      including 987 patients in complete remission without brain metastases or prior
      brain irradiation showed statistically significant effect in favour of PCI on
      survival, disease free survival, and risk of brain metastases (relative risks
      being 0.84, 0.75, and 0.46, and p-values being 0.01, < 0.001, and < 0.001,
      respectively). Two randomised trials evaluated neurotoxicity in totally 350
      patients before PCI and found abnormalities in 24-60%. Repeated examination
      during the following years revealed no differences on cerebral CT-scans or
      neuropsychological testing between PCI patients or controls. A review including
      42 PCI trials with 4,749 patients revealed the optimal total radiotherapy dose to
      be 30-35 Gy given as 2 Gy fractions. Also 24 Gy in 3 Gy fractions appear safe
      based on data from a large randomised study. Both the former study and the meta
      analysis suggested early PCI to be better than late. CONCLUSIONS: PCI improves
      both overall and disease free survival and decreases the risk for brain relapse
      in SCLC patients in complete remission. PCI should be applied early, and useful
      and safe doses may be 30-36 GY in 2-3 Gy fractions, though future studies may
      further illuminate the optimal dose, fractionation and timing.

PMID- 14635502
TI  - Exercise physiology in COPD.
AB  - Multiple mechanisms contribute to exercise limitation in chronic obstructive
      pulmonary disease (COPD). The ability to increase ventilation during exercise is
      reduced; the more advanced the disease, the more impaired the exercise tolerance
      is. However, factors other than ventilatory limitation play an important role in
      reducing the exercise capacity in COPD. Data implicating peripheral muscle
      atrophy and muscle weakness as cofactors have been reported in individuals with
      advanced disease. At this stage daily activities are curtailed to avoid
      exertional respiratory discomfort. Recent studies have demonstrated that the
      muscle aerobic capacity of stable hypoxemic COPD patients is impaired; oxygen
      uptake (V'O2) kinetics and 31P magnetic resonance spectroscopy studies have shown
      that these patients rely heavily on non-aerobic energy sources even during
      moderate, sustained workloads. Finally, early occurrence of metabolic acidosis
      has been demonstrated in patients with mild to severe COPD during exercise.
      Inadequate tissue oxygenation appears to result from a defect in peripheral
      oxygen utilization rather than from a reduction in O2 bulk flow. Peripheral
      factors may include: a) impaired diffusive conductance for O2 between red cells
      and mitochondria; b) heterogeneous distribution of O2 bulk flow within the
      exercising muscle fibers; c) inertia of the oxidative processes at the cellular
      level; d) changes in distribution of muscle fibers, e) reduction in muscle
      aerobic enzymes; and f) poor nutritional status. Since muscle dysfunction has an
      important role in the development of exercise intolerance, physical
      rehabilitation is more and more used as part of the treatment of COPD. The aim of
      this review is to briefly discuss current views on the mechanisms responsible for
      the reduced ability to exercise and the rationale for exercise rehabilitation in
      COPD patients.

PMID- 14635503
TI  - The conversion of thyroxine to triiodothyronine in the lung: comparison of
      activity of type I iodothyronine 5' deiodinase in lung cancer with peripheral
      lung tissues.
AB  - Triiodothyronine (T3) is the main active hormone, which is derived 20% from the
      thyroid gland and 80% from peripheral tissues. Thyroxin--5' deiodinases play a
      leading role in maintaining appropriate T3 concentrations in the different cells
      and organs: including the lung. The deiodinases present in pneumocytes were found
      to be localised in endoplasmatic reticulum. Aims of this study were: 1. To
      estimate activities of Type I and Type II iodothyronine 5' deiodinases (DI, DII)
      in two histological types of lung cancer. 2. To investigate possible differences
      in DI and DII activities between tumour tissue and peripheral lung tissue. 3. To
      study whether DI and DII activities are related to the extent of the disease
      process and grade of differentiation of lung cancer. MATERIAL: We studied 44
      patients undergoing thoracotomy due to lung cancer. Histologically: 23 pts-
      squamous cell cancer, 21 pts adenocarcinoma. In all patients both tumour and
      peripheral lung tissue were studied. DI activity was measured in pmol 1251-
      released from 125 IrT3/min/mg of proteins, DII activity--in fmol 125I- released
      from 125IT4/hour/mg of protein. RESULTS: In most specimens DI and DII activities
      were observed. DI activity in specimens from lung peripheral tissue was: 3.3-58.3
      pmol/min/mg of protein (mean 22.20) and in lung cancer tissue was: 2.0-44.7
      pmol/min/mg of proteins (mean 13.3). DII activity in lung peripheral tissue
      ranged from 19 to 242 fmol/h/mg protein (mean 94.4) and in lung cancer ranged
      from 21 to 253 fmol/h/mg protein (mean 107.9). CONCLUSIONS: 1. Conversion of T4
      to T3 occurs also in the lung. 2. The activity of DI is statistically
      significantly lower, in lung cancer than in peripheral lung tissue (13.3 +/- 9.5
      vs 22.20 +/- 13.4 pmol/min/mg protein) respectively, p < 0.001. 3. DII activity
      in lung is present and similar in peripheral lung and lung cancer tissue. 4.
      There is a non-significant trend for correlation of DI activity and grade of
      differentiation (G1-G3) of tumour tissue and stage of lung cancer. Abbreviations'
      list: T3--triiodothyronine, T4--thyroxine, FT4--free thyroxine, rT3--revers
      triiodothyronine TSII--Thyroid Stimulating Hormone Type I lodothyronine
      5'deiodinase = type I 5'deiodinase = 5'DI = DI Type II Iodothyronine 5'deiodinase
      = typeII 5'deiodinase = 5'DII = DII E.S.S.--Euthyroid Sick Syndrome, hDII = human
      type II iodothyronine deiodinase HDII-b, hDII-c = two novel splice variants SCC-
      Squamous Cell Cancer, A--adenocarcinoma, BMI--Body Mass Index BSA--Bovine
      Standard Albumin, DTT-1,4 Dithio-L-treitol, PTU--Propylothiouracil TCA-
      Tricholoroacetic Acid, TNM--Tumour Nodule Metastases (class.) G1-G3-grade of
      differentiation, COPD--Chronic Obstructive Pulmonary Disease.

PMID- 14635504
TI  - National mesothelioma incidence and the past use of asbestos.
AB  - In Western Europe, Scandinavia, North America and Australia the manufacture and
      use of asbestos products peaked in the 1970's. The current incidence of
      mesothelioma ranges from 14 to 35 cases/million/year in eleven industrialized
      countries which had used asbestos 2.0 to 5.5 kg/capita/year about 25 years
      earlier. A significant linear correlation (r = 0.80, p = 0.01) exists between the
      two variables. Accordingly, about 170 tons of produced and consumed asbestos will
      cause at least one death from mesothelioma, most often as a consequence of
      occupational exposure.

PMID- 14635505
TI  - The effect of inhaled furosemide and acetazolamide on bronchoconstriction induced
      by deep inspiration in asthma.
AB  - In some asthmatics deep inspiration causes a sustained bronchoconstration, which
      is dependent on Ca2+ uptake. Inhaled diuretics protect against
      bronchoconstriction induced by a variety of indirect stimuli, by inhibiting the
      ionic fluxes involving Ca2+ uptake across the cell membrane of airway epithelium.
      The aim of this study was therefore to investigate the protective effect of
      inhaled furosemide on the bronchoconstriction induced by deep inspiration in
      asthma and to compare it with the effect of acetazolamide, an inhibitor of
      carbonic anhydrase devoid of effect on ion cotransport but possessing inhibitory
      effects on chloride ion influx and Na+/K+ exchange. The study was carried out on
      three different study days according to a randomized, double-blind, placebo
      controlled, crossover design. Nine non smoking asthmatic subjects first performed
      a series of 9 controlled deep inspirations to TLC followed by forced expirations
      to RV within 20 min, which caused a decrease of FEV1 > 20% from baseline. Two
      hours later, the subjects inhaled either furosemide (40 mg), or acetazolamide
      (500 mg), or saline (placebo) in random order, and then two more deep-inspiration
      challenges were performed after 30 and 140 mins. The progressive percent
      decrement of FEV1 caused by deep-inspiration challenge was taken as an index of
      bronchoconstriction. Bronchoconstriction was significantly blunted at 30 mins,
      but not 140 mins, after inhaling furosemide (p < 0.01) or acetazolamide (p <
      0.05) compared to control. We interpret these results as due to a modulation of
      ionic fluxes across the smooth muscle cell membrane afforded by inhaled
      furosemide and acetazolamide.

PMID- 14635506
TI  - The diagnostic and screening capacities of peak expiratory flow measurements in
      the assessment of airway obstruction and bronchodilator response in children with
      asthma.
AB  - Although the measurement of peak expiratory flow (PEF) is frequently used in
      general practice as a surrogate for forced expiratory volume in one second (FEV1)
      in the assessment of airway obstruction and bronchodilator response (BDR), its
      use has never been validated in children with asthma. Spirometry and PEF
      measurements (mini-Wright peak flow meter) were performed in 271 children with
      asthma who attended the hospital for a routine pulmonary evaluation. Airway
      obstruction was defined as FEV1 as a percentage of predicted (FEV1% pred) < 80%;
      a positive BDR was defined as an increase in FEV1% pred > or 9% after inhaling
      800 micrograms salbutamol. The Spearman correlation coefficient between the
      percent-predicted values of PEF (PEF% pred) and FEV1% pred was 0.36, Commonly
      used cut off values for airway obstruction of PEF% pred < 75% and PEF% pred < 80%
      had a high specificity (95%, 91%) and NPV (95%, 95%), but a moderate sensitivity
      (54%, 57%) and PPV (54%, 41%). After administration of the bronchodilator, the
      Spearman correlation coefficient between the different expressions of delta PEF
      and delta FEV1% pred ranged between 0.52 and 0.54. Commonly used cut off values
      for BDR of delta PEF% init (increase in PEF as percentage of initial value) > or
      = 20% and delta PEF% init > or = 25% had a high specificity (96%, 96%), a
      reasonable NPV (74%, 69%) and PPV (74%, 85%), but a moderate sensitivity (51%,
      53%). In conclusion, PEF testing has the properties to be a good screening test
      to exclude airway obstruction and BDR (high specificity and NPV), but is of less
      clinical value as a diagnostic test (moderate sensitivity and PPV).

PMID- 14635507
TI  - Sleep-related breathing disorders in amyotrophic lateral sclerosis.
AB  - Sleep-related breathing events in patients with amyotrophic lateral sclerosis
      (ALS) have been reported in small case series, but the association with the
      clinical presentation--with (B) or without (nonB) bulbar symptoms--or the
      relevance for prognosis have not been investigated. We retrospectively analyzed
      sleep studies of 114 (46 nonB) ALS patients, aged 54 +/- 11 years. Respiratory
      function was better in nonB patients: forced vital capacity was 76 +/- 20% vs 55
      +/- 23% in the bulbar group (p < 0.001); PaCO2 41 +/- 5 vs 44 +/- 6 mm Hg p <
      0.05. The mean apnea/hypopnea index (AHI) was higher in nonB patients (22 +/- 12
      vs 15 +/- 16 events per hour- p < 0.05); in this group 21 out of 46 patients
      (46%) had more than 20 events/hour versus 14 out of 68 (21%) in the nonB group (p
      < 0.005). On the contrary the oxygen desaturation index (ODI) was similar (10 +/-
      11 vs 9 +/- 12 events per hour, p = NS). Most events had a central genesis and
      obstructive events were usually erratic, except in 7 patients (6 in group B) who
      had more than 10 obstructive events/hour. Data were stratified in three groups:
      with a disease duration below 1 year (< 1 yr), between 1 and 2 years (1-2 yr),
      and more than 2 years (> 2 yr). The occurrence of sleep-related respiratory
      disorders decreased with the increase of disease duration (23 +/- 15; 18 +/- 14;
      and 16 +/- 15 events per hour respectively), the decrease being significantly
      lower in the > 2 yr group than in the < 1 yr (p < 0.05). Again ODI was similar in
      the three groups. In conclusion the present study shows that sleep-related
      breathing events are more common than previously described in ALS patients,
      particularly in the first year following onset of the disease. Obstructive events
      occur rarely, although the prevalence of obstructive sleep apnea is higher than
      predicted, particularly when bulbar symptoms are present. Patients without bulbar
      signs show a higher prevalence of central events. The progressive decrease of
      events with the increase of disease duration could be due to a progressive
      weakness of respiratory muscles, but it could also suggest an independent role
      for nocturnal events which could be linked to a worse prognosis or to a more
      rapid decay of clinical status.

PMID- 14635508
TI  - Localized benign pleural mesothelioma: a case report.
AB  - Primary neoplasms of the pleura are rare tumors and the majority are generally
      mesotheliomas. Mesotheliomas are either localized and mostly benign, or diffuse
      and uniformly malignant neoplasms. Localised benign pulmonary mesothelioma
      (solitary fibrous tumor of the pleura) are originally thought to be a variant of
      diffuse pleural mesothelioma because they consists of a spindle cell stroma
      associated with branching tubular structures lined by cuboidal cells. Our case
      which is reported below shows the clinical spectrum of the more common benign
      variant. Clinical differential diagnosis of benign and malign mesotheliomas is
      not clear. Complete surgical resection is the preferred treatment for both types
      and usually curative with the benign mesothelioma. The localised pleural variant
      is benign in most cases, and it is even less common, constituting only 10% of all
      mesotheliomas [1]. The importance of localised benign mesothelioma is that it is
      almost impossible to differentiate from a malignant neoplasm preoperatively and
      it may occasionally recur, sometimes with a malignant change.

PMID- 14635509
TI  - A case of indirect exposure to cat at school.
AB  - Indirect exposure to cat allergens may exacerbate asthma in sensitized subjects.
      We report a case of a 13-year-old girl referred to our Unit for cough, dyspnea,
      wheezing, chest tightness, nasal itching and obstruction during the past six
      months, with improvement during summer holidays. Skin prick tests were positive
      for cat and Alternaria alternata. She had no cats at home. Spirometry was normal
      and methacoline bronchial challenge was negative. PEF monitoring showed a mean
      value of 80% of the predicted value with a variability higher than 20% in a few
      occasions. At a follow up visit PEF recording showed an increase of 80 litres/min
      during a 2 weeks Christmas holidays, and a subsequent reduction after being back
      at school. At a further questioning we found that in her class there was a girl
      who owned 23 cats. It is likely that PEF and symptoms in our patient were
      affected by indirect cat exposure at school.

PMID- 14635511
TI  - [Neurotrophic factors: functions and potentials for clinical use].

PMID- 14635510
TI  - Predictive factors in smoking cessation with combined therapy with bupropion and
      nicotine patches.
AB  - The association of bupropion and nicotine is a good choice in the treatment of
      smoking cessation. However, not all patients actually give up smoking. STUDY
      OBJECTIVES: This work was undertaken with the aim of finding out the functional
      or clinical variables that could be associated with the success of the cessation
      therapy. DESIGN: In one year, 88 patients who were treated with bupropion 300
      mg/day and nicotine patches were followed-up, for 1 month and 3 months,
      respectively. They were all questioned about the number of cigarettes per day,
      the years they have been smoking, the number of quitting attempts, and concurrent
      pulmonary conditions were sought for. The Fagestrom Test, forced spirometry (FVC,
      FEV-1, FEF25-75), and exhaled carbon monoxide (by co-oxymetry) were also
      assessed. For the statistical analysis, a logistic regression model allowing to
      predict the response of new subjects to the treatment, with the lowest error
      possible, was applied. To choose the working model, the highest and lowest value
      of each variable were found, drawing the correlation matrix between dependent and
      independent variables, by means of the box-plot procedure. Then, the model's
      application conditions were analysed: linearity, homoscedasticity, independence
      of the applications, and normality of the distributions. To assess the
      discrimination of the model, a ROC curve was used. RESULTS: Showed that at the
      end of the follow-up year, 59.1% of the patients quitted smoking. The
      multivariate analysis with logistic regression showed that no previous history of
      chronic obstructive pulmonary disease (COPD), a FEF25-75 value and effectively
      quit after the first week of treatment were independent prognostic factors of
      treatment success. When the diagnosis precision of our model was analysed by
      means of the ROC curve, it showed a 78% value, with the 95% confidence interval
      ranging from 68.5% to 86.9%. At the optimal cut-off point of our model,
      sensitivity and specificity for quitting smoking were found to be 66.7% and 80%,
      respectively. CONCLUSIONS: We conclude that with a diagnosis precision of 78.8%
      patients with no history of COPD, who quitted at the first week of therapy with
      bupropion and with low FEF25-75, will remain non-smokers after one year follow
      up. Contrarily, COPD patients who still smoke after one week of therapy, will not
      achieve quitting smoking.

PMID- 14635512
TI  - [Neurotrophic factors and amyotrophic lateral sclerosis (ALS)--therapeutic
      potential of a new neurotrophic factor: HGF in ALS].

PMID- 14635513
TI  - [Glial cell line-derived neurotrophic factor for the rescue of dopaminergic
      neurons in Parkinson's disease].

PMID- 14635514
TI  - [Neurodegenerative diseases and Dorfin].

PMID- 14635515
TI  - [Unawareness for homonymous visual field defect].
AB  - BACKGROUND: There was no report which dealt with the relationship between
      emotional state, degree of defective visual search, severity of hemianopic
      dyslexia, the episode when the patient became aware of the defect, and
      unawareness of visual loss in homonymous hemifield. OBJECTIVE: To investigate the
      relationship between degree of awareness and those factors that might be
      responsible for the unawareness, including the aspects listed above. METHODS:
      Four patients with visual field defects caused by a brain lesion after a stroke
      was investigated. Self rating of emotional state, search performance for an
      object among many placed on a table, and for text reading, as well as visual
      field, visual positive phenomena, and hemispatial neglect were evaluated. Degree
      of unawareness for field loss was evaluated by modified version of the method of
      Bisiach et al. (1985). In addition, the episodes when the patient became aware of
      the defect were asked. RESULT: In accordance with the previous studies, we found
      no relationship between the degree of awareness of field defect and anatomic
      lesions, co-existence of hemispatial neglect, or the degree of awareness of
      hemiplegia. However, the patient with neglect was unaware of their troubles in
      vision at all, whereas the patients without neglect were aware of the troubles
      but misinterpreted them as problems of the eyes including acuity. In accordance
      with previous studies, co-existence of visual hallucinations or illusions seemed
      to be associated with awareness of visual field defect. No relationship was found
      between the degree of awareness of field defect and emotional state, degree of
      field loss, degree of defective visual search, or severity of hemianopic
      dyslexia. Their responses to the inquiry about the degree of awareness of field
      defect were not consistent. Thus, the awareness of the field defect seemed to be
      difficult to be kept firmly in their mind. On the other hand, the patients could
      remember the episode when they became aware of the defect for the first time,
      being able to specify time, place, and situation. CONCLUSION: Levine (1990)
      suggested that the sensory loss in this sort of patients was never phenomenally
      immediate but instead must be discovered by observation and inference. Non
      specificity of the lesion, qualitative difference in awareness between the
      patient with and without hemispatial neglect, association of positive visual
      phenomena and awareness, fluctuation of awareness, and dependence of awareness on
      personal experiences found in our patients, can be explained with this
      'discovery' hypothesis.

PMID- 14635516
TI  - [A case of bilateral lower pons-medial medullary infarction presenting
      quadriparesis].
AB  - Bilateral medial medullary infarction is rare. Only 18 cases have been reported
      previously. We experienced a case of the bilateral lower pons-medullary
      infarction. A 63-year-old woman was admitted to our hospital because of moderate
      left hemiparesis. Hyperreflexia in left limbs and positive Babinski's reflex in
      left foot was observed. Sensory disturbance was mild left hemihypesthesia (in
      light touch, postural sense and vibration) without facial involvement. She also
      had lateral gaze nystagmus, dysarthria, and bilateral decreased gag reflex.
      Respiratory failure was not observed. A conservative therapy for cerebral
      infarction was performed. But the hemiparesis was deteriorated and progressed to
      complete quadriparesis on the 5th day. The brain MRI (T2-weighted image and
      FLAIR) demonstrated bilateral lower pons-medial medullary infarction on the 9th
      day. Cerebral angiography and 3D-CT angiography revealed no stenosis or
      occlusions in the major cerebral arteries. The anterior spinal artery was not
      evaluated enough because of the arteriosclerosis. The prognosis of this patient
      was favorable except for the quadriparesis. The severe quadriparesis has not been
      improved for about 2 years. The bilateral medial medullary infarction was quite
      rare in the literature. The prognoses of these cases were unfavorable for the
      respiratory failure. Our case was not fatal because of no respiratory paralysis.

PMID- 14635517
TI  - [Neuropsychiatric systemic lupus erythematosus associated with anti-phospholipid
      syndrome, showing massive intracranial calcifications].
AB  - We report a 46-year-old woman who extensively showed intracranial calcifications
      possibly due to neuropsychiatric systemic lupus erythematosus (NPSLE) and
      antiphospholipid syndrome (APS). She had been treated with oral prednisolone for
      SLE since age 15, and experienced two abortions due to APS at ages 28 and 35
      respectively. After a convulsion attack due to NPSLE at age 30, she had been
      suffering from dysarthria and choreic movement in her extremities. On admission
      to our hospital brain CT demonstrated extensive and symmetrical calcifications
      bilaterally in basal ganglia, subcortical white matter of the frontal lobe and
      dentate nuclei. She was shown to have neither metabolic nor congenital disorders
      causing these intracranial abnormalities. In this patient both NPSLE and APS,
      therefore, might have contributed to the remarkable intracranial calcifications
      in a long clinical course.

PMID- 14635518
TI  - [Gliomatosis cerebri: report of 3 cases and review of recent literatures].
AB  - Gliomatosis cerebri is a rare tumor of the central nervous system characterized
      by widespread diffuse infiltration of the brain and spinal cord by neoplastic
      glial cells. The diagnosis of gliomatosis cerebri with MR imaging remains
      difficult. We presented three interesting cases of gliomatosis cerebri. Case 1
      showed transformation from type 1 gliomatosis cerebri to type 2. Case 2 showed
      that the initial thalamic lesion extended into brain stem, cerebellar hemisphere
      and right cerebral hemisphere. After radiation therapy, the right cerebral cortex
      demonstrated hyperintensity on T1- and hypointensity on T2-weighted image. These
      two cases did not demonstrate diffuse brain swelling or indistinctness of
      gray/white matter border on the first MR imaging. Case 3 showed two histological
      components of oligodendroglioma in the corpus callosum and astrocytoma in the
      cingulate gyrus. Case 3 improved in response to radiotherapy and chemotherapy
      using procarbazine/MCNU/vincristine (MVP). We also reviewed recent literatures.

PMID- 14635519
TI  - [Wilson's disease associated with olfactory paranoid syndrome and idiopathic
      thrombocytopenic purpura].
AB  - In this study we report an individual of Wilson's disease associated with
      olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial
      symptom of this female patient was olfactory paranoia at age 17. Although that
      psychiatric symptom was well controlled under pharmacological treatment for two
      years, she developed olfactory paranoia as well as sialorrhea, dysarthria and
      finger tremor at age 20. A year later rigidity was also present in the
      extremities. At age 23, idiopathic thrombocytopenic purpura was found based on
      hematological examinations. Because her extrapyramidal symptoms were progressive,
      she was referred to our department to evaluate her neurologic condition. She was
      diagnosed as having Wilson's disease based on (1) the presence of Kayser
      Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum
      copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense
      lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images
      also showed hyperintense lesions in the thalamus and pontine tegmentum. The
      biopsy specimen of the liver revealed chronic hepatitis with copper accumulation.
      Since D-penicillamine treatment was initiated, she has shown no olfactory
      paranoia and exacerbation of ITP. Her gait disturbance has also improved.
      Olfactory paranoia and ITP are rare clinical complications of Wilson's disease.
      Further analysis may warrant consideration of the pathophysiological mechanism of
      the psychiatric, hematological and neuroradiological condition seen in Wilson's
      disease.

PMID- 14635520
TI  - [Thrombosed giant aneurysm of the pericallosal artery: case report and MR
      imaging].

PMID- 14635521
TI  - [Diagnosis of subarachnoid hemorrhage in subacute phase by using MRI].

PMID- 14635523
TI  - [Molecular mechanisms of insulin secretion].

PMID- 14635522
TI  - [Pancreatic beta-cell death, regeneration and functioning].

PMID- 14635524
TI  - [Diabetes mellitus and endoplasmic reticulum stress].

PMID- 14635525
TI  - [Mechanism of insulin action and diabetes mellitus].

PMID- 14635526
TI  - [Genetic susceptibility of type 2 diabetes].

PMID- 14635527
TI  - [Molecular mechanism of diabetic angiopathy].

PMID- 14635528
TI  - Cervical cytological screening and human papillomavirus DNA testing in Flanders.
AB  - The causal relationship between genital human papillomavirus (HPV) infection and
      cervical dysplasia/carcinoma has been recognised for some time. The aim of this
      study was to document the occurrence and distribution of HPV infection in the
      five provinces of the Flemish region in Belgium and to correlate the HPV DNA test
      results with the cytological results on simultaneously performed thin layer
      preparations of cervical cells. Out of a total screened group of 105107 samples,
      1978 samples with cytological abnormalities were tested for HPV DNA using the
      MY09/MY11 consensus PCR. The mean age of the whole group was 36.9 years. The LSIL
      group, with a mean age of 33.6 years, was significantly younger than the other
      groups. There was no significant difference in HPV prevalence among the
      provinces. In four out of five provinces the HPV prevalence reached 100% in high
      grade lesions. There is a significant increase in predominance of high-risk HPV
      types, with increasing abnormal cytology (17.9% WNL < 51.1% ASCUS < 83.8% LSIL <
      97.2% HSIL). Three peaks of HPV DNA positivity were observed, a first at 22 yrs
      (82%), a second at 47 yrs (60%) and a third in women older than 65 yrs (52%).
      These results shed more light on HPV prevalence in Flanders and show that the
      MY09/MY11 consensus primer based detection system is very suitable for the
      detection of HPV infections in Flanders.

PMID- 14635529
TI  - Combined impact of mucosal damage and of cystic fibrosis on the small intestinal
      brush border enzyme activities.
AB  - In 61 cystic fibrosis (CF) patients, the small intestinal mucosa was studied at
      the time of diagnosis before starting therapy. In 19 out of 61 patients, partial
      villous atrophy on light microscopy and shortened villi on stereomicroscopic
      examination were seen. On the biopsy specimens, maltase, sucrase, lactase and
      alkaline phosphatase activities were studied. Comparison of the enzymatic
      activities in CF patients having damaged mucosa and a group of patients having
      similar mucosal lesions of unspecified origin (UTID), reveals a significantly
      more pronounced decrease of the alkaline phosphatase activity (p < 0.005) in the
      CF patients. This is in agreement with previous reported results in CF patients
      with normal mucosa. The abnormal mucosal findings could be due to the decreased
      neutralization of the gastric content delivered into the duodenum, the early
      inflammatory reaction present in the CF mucosa and/or to the impaired synthesis
      of membrane glycoproteins and enzymes secondary to the CFTR mutation.

PMID- 14635530
TI  - The use of hypnosedative drugs in a university hospital setting.
AB  - OBJECTIVE: The use of hypnosedatives (HSs) in the hospital and at home before
      admission was registered. Also, the incidence of HSs newly started in the
      hospital and the incidence of withdrawal in chronic users while in hospital was
      recorded. METHODS: The study population consisted of 517 consecutively admitted
      patients recruited from 10 wards of the Ghent University Hospital; 493 of them
      received a questionnaire and were interviewed concerning the use of HSs at home
      and in the hospital, about the cause and duration of treatment, the type of HSs
      used, the presence and nature of any concomitant sleep or anxiety disorder. Main
      outcome measures were the actual use of HSs during hospitalisation as compared
      with the reported use, the influence of hospitalisation on use of HSs and the
      assessment of cause and duration of use of HSs. RESULTS: Twenty-nine percent of
      the study sample took HSs at home and 45.2% while in the hospital. HSs were
      prescribed to 28.6% of the patients not habituated to chronic use of HSs at home.
      In contrast, 14.0% of the patients habituated to chronic use of HSs received no
      sleep medication while in hospital. Patients older than 60 years used more HSs
      than younger patients. Previous administration of HSs, sleep problems during
      hospital admission and female sex were predictive of HS-use. The main reason for
      prescription of HSs in the hospital was continuation of HSs taken at home. The
      most prescribed HSs were: lormetazepam, lorazepam, alprazolam, diazepam and
      zolpidem. Almost 10% of the patients were not informed on treatment with HSs.
      Among the subjects in whom HSs were newly started, 16.0% intended to continue
      this medication after discharge. Eleven percent took combinations of
      hypnosedative drugs. CONCLUSIONS: The prevalence of prescription of HSs in the
      university hospital setting is high. Appropriate guidelines are needed to control
      the use of HSs during hospitalisation and to ensure withdrawal from these drugs
      upon discharge.

PMID- 14635531
TI  - ELISA D-dimer measurement for the clinical suspicion of pulmonary embolism in the
      emergency department: one-year observational study of the safety profile and
      physician's prescription.
AB  - OBJECTIVES: To validate the safety profile of a rapid ELISA D-dimer as the first
      diagnostic step in the clinical suspicion of pulmonary embolism (PE) in
      outpatients admitted to an emergency department (ED), and to retrospectively
      evaluate the appropriateness of the physician's prescription. DESIGN AND SETTING:
      An observational study of all patients admitted to the ED of an urban university
      teaching hospital with signs and symptoms justifying the prescription of a rapid
      ELISA D-dimer measurement (Vidas; Biomerieux; France) as the first line
      diagnostic test for PE. Acute PE was established or excluded according to an
      appropriate combination of the D-dimer concentration, the lung scintigraphy, the
      spiral computerized tomography (spiral CT), the venous ultrasonography, and the
      arteriography in case of uncertain results. All patients with D-dimer values
      under the cut-off point of 500 ng/ml were followed up after 6 months. RESULTS:
      395 patients were studied. A normal D-dimer concentration < 500 ng/ml was found
      in 179 patients (45% of the cohort). The retrospective analysis showed that none
      of these patients were found to have a high pre-test clinical probability. None
      of these 179 patients received anticoagulation nor displayed a PE event during a
      6-month period (negative predictive value 100%; 95% CI, 98.0 to 100%; sensitivity
      100%; 95% CI, 90.3 to 100%). Among the 216 patients (55%) with D-dimer values
      above 500 ng/ml, PE was confirmed in 32 cases, for a prevalence of the disease of
      8.1%. Eighty-six patients (22%) had no additional testing in spite of positive D
      dimer values > 500 ng/ml, pointing out a 22% rate of inappropriate use of the D
      dimer measurement. CONCLUSION: This observational study confirms that a normal
      rapid ELISA D-dimer value (< 500 ng/ml) used as a first diagnostic step in ruling
      out the diagnosis of PE is a safe clinical practice when the pre-test clinical
      probability is low or intermediate. Nevertheless, the low prevalence rate of the
      disease (8.1%) suggests a potential overused and inappropriate prescription.

PMID- 14635532
TI  - An unusual cause of abdominal pain.
AB  - A 36-year-old woman presented to the Emergency Room because of abdominal pain
      associated with hematuria and red blood blending to stool. On admission, the
      physical examination revealed abdominal tenderness and diffuse cutaneous
      hematoma. The laboratory findings showed abnormal clotting tests with high
      International Normalised Ratio (INR) and prolonged activated partial
      thromboplastin time. Hemoperitoneum and ureteral hematoma were noted on the
      abdomen computed tomography. The patient confessed she had ingested difenacoum
      for several weeks. All the symptoms resolved with fresh frozen plasma perfusion
      and vitamin K.

PMID- 14635534
TI  - beta 2 M-amyloidosis and gastrointestinal bleeding after renal transplantation.
AB  - Dialysis-related amyloidosis is a disorder that commonly develops in long-term
      dialysis with an incidence that is linked to the duration of hemodialysis. The
      amyloid deposits are composed of the amyloid precursor beta 2 microglobulin,
      mainly affecting the osteoarticular system, but also involving extra
      osteoarticular tissues. We present a patient with repeated rectal bleeding caused
      by a circumferential atone ulcer in the immediate posttransplantation period due
      to the use of a rectal canula after 27 years of treatment with hemodialysis.
      Histopathological examination of the rectal ulcer biopsy specimens revealed
      positive Congo red stain and additional immunohistochemical investigation showed
      the presence of beta 2-microglobulin in a blood vessel wall of the rectum.
      Although dialysis related amyloidosis may be partially prevented, it is important
      to remain alert for dialysis related amyloidosis complications after renal
      transplantation in patients with a longstanding history of dialysis.

PMID- 14635533
TI  - Limited Wegener's disease initially misdiagnosed as tuberculosis.

PMID- 14635536
TI  - Palliative care--from dream to mainstream.

PMID- 14635535
TI  - [Hypertension in rural population: Risk factors and treatment with
      antihypertensive agents].

PMID- 14635537
TI  - Patient population movement in a Cape Town obstetric service.

PMID- 14635538
TI  - Israel, Iraq, Zimbabwe--should we care?

PMID- 14635539
TI  - Rural radiology in central Africa.

PMID- 14635540
TI  - Aid for AIDS--at last.

PMID- 14635541
TI  - Cuban doctors get raw deal.

PMID- 14635542
TI  - Preventing cervical cancer: Denny scoops technology Woman of the Year.

PMID- 14635543
TI  - AIDS survivor sketches treatment pitfalls.

PMID- 14635544
TI  - TB investment--more than just gilding Eli's Lilly.

PMID- 14635545
TI  - Patients can take control of their medical expenses.

PMID- 14635546
TI  - Failure to take prescribed medicine for chronic diseases is a massive, worldwide
      problem.

PMID- 14635547
TI  - Board of Healthcare Funders of SA.

PMID- 14635548
TI  - Guidelines for ethical decisions. 3.

PMID- 14635550
TI  - Launching the ARV roll-out debate into the public arena.

PMID- 14635551
TI  - Smoking among nursing staff at Tygerberg Hospital, Cape Town.

PMID- 14635552
TI  - Traditional healers and paediatric care.

PMID- 14635553
TI  - Proximal oesophageal strictures in a child with HIV disease.

PMID- 14635554
TI  - Renal transplantation in South Africa.

PMID- 14635555
TI  - Participant remuneration for research--how much is enough?

PMID- 14635556
TI  - Accuracy of menstrual history in early pregnancy.

PMID- 14635557
TI  - Initial burden of disease estimates for South Africa, 2000.
AB  - BACKGROUND: This paper describes the first national burden of disease study for
      South Africa. The main focus is the burden due to premature mortality, i.e. years
      of life lost (YLLs). In addition, estimates of the burden contributed by
      morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate
      disability-adjusted life years (DALYs); and the impact of AIDS on premature
      mortality in the year 2010 is assessed. METHOD: Owing to the rapid mortality
      transition and the lack of timely data, a modelling approach has been adopted.
      The total mortality for the year 2000 is estimated using a demographic and AIDS
      model. The non-AIDS cause-of-death profile is estimated using three sources of
      data: Statistics South Africa, the National Department of Home Affairs, and the
      National Injury Mortality Surveillance System. A ratio method is used to estimate
      the YLDs from the YLL estimates. RESULTS: The top single cause of mortality
      burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents
      and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately
      higher for females (47%) than for males (33%). Pre-transitional diseases, usually
      associated with poverty and underdevelopment, accounted for 25%, non-communicable
      diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that
      mortality alone underestimates the burden of disease, especially with regard to
      unintentional injuries, respiratory disease, and nervous system, mental and sense
      organ disorders. The impact of HIV/AIDS is expected to more than double the
      burden of premature mortality by the year 2010. CONCLUSION: This study has drawn
      together data from a range of sources to develop coherent estimates of premature
      mortality by cause. South Africa is experiencing a quadruple burden of disease
      comprising the pre-transitional diseases, the emerging chronic diseases,
      injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay
      morbidity become widely available, the burden due to HIV/AIDS can be expected to
      grow very rapidly in the next few years. An improved base of information is
      needed to assess the morbidity impact more accurately.

PMID- 14635558
TI  - Impact of age, gender and race on patient and graft survival following renal
      transplantation--developing country experience.
AB  - BACKGROUND: Optimising renal allograft survival is crucially important in
      developing countries because of limited resources to treat irreversible renal
      failure. However, although many factors can be manipulated to improve outcome,
      certain demographic factors are immutable in individual patients. The present
      study evaluated the impact of age, gender and race on the outcome of renal
      transplantation. METHODS: Relevant data were reviewed for 542 patients receiving
      primary renal allografts over a 23-year period. The survival of patients and
      grafts were calculated using the Kaplan-Meier method. Both univariate and
      multivariate analyses were used to determine the association between the
      demographic factors and patient and graft survival. RESULTS: Actuarial survival
      of both patients and grafts decreased with increasing age. The most striking
      differences were demonstrated when patients older than 40 years were compared
      with younger patients. However, when patient survival was censored for death with
      functioning grafts--a very important cause of graft loss--then actuarial graft
      survival improved with increasing age. There was no gender difference in graft
      survival, but female recipients of renal allografts had a higher mortality than
      their male counterparts. There were no racial differences in either patient or
      graft survival. CONCLUSIONS: Age is an important determinant of outcome after
      renal transplantation, but race is not. Gender does not influence graft survival,
      but females do have a higher overall mortality rate following renal
      transplantation at our centre.

PMID- 14635559
TI  - Overt hypoadrenalism is uncommon in patients with stage 3 and 4 bronchogenic
      carcinoma.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer mortality in most
      countries. The adrenal glands are common sites of metastatic lung cancer as
      approximately 40% of subjects with stage 4 bronchogenic carcinoma have adrenal
      metastases. The prevalence of biochemical hypoadrenalism is, however, remarkably
      poorly documented. OBJECTIVES: Our study aimed to determine the prevalence of
      primary hypoadrenalism, as defined by a subnormal cortisol response to the 250
      micrograms adrenocorticotrophic hormone (ACTH) stimulation test, in patients with
      stage 3 and 4 lung cancer. METHODS: Thirty patients with stage 3 and 4
      bronchogenic carcinoma were prospectively recruited from the bronchus clinic.
      Demographic data and electrolytes were recorded and each patient had a 250
      micrograms ACTH stimulation test to determine the prevalence of overt adrenal
      insufficiency, defined as a +30 minute cortisol of less than 550 nmol/l. RESULTS:
      The median age and quartile deviation was 62 (10) years and the median basal
      cortisol was 429.5 (321) nmol/l. The median peak cortisol was 828.5 (342) nmol/l
      (range 536-1,675 nmol/l). Twenty-eight patients (93.3%) had an appropriate rise
      of cortisol to greater than 550 nmol/l following 250 micrograms ACTH stimulation.
      Two patients (6.7%) had mild primary adrenal failure with a peak cortisol between
      500 and 550 nmol/l associated with a raised plasma ACTH concentration (131.4 and
      10.5 pmol/l, normal 2.2-10 pmol/l). Twenty-eight patients (92.9%) were
      normonatraemic, while the two hyponatraemic patients had biochemical evidence of
      the syndrome of inappropriate antidiuretic hormone secretion. CONCLUSION: In
      conclusion, despite evidence that the adrenal glands of patients with
      disseminated bronchogenic carcinoma are frequently affected by metastatic
      disease, biochemical evidence of clinically significant hypoadrenalism is
      relatively uncommon and is not accurately predicted by electrolyte abnormalities.

PMID- 14635560
TI  - Severe acute maternal morbidity and maternal death audit--a rapid diagnostic tool
      for evaluating maternal care.
AB  - OBJECTIVE: To analyse severe acute maternal morbidity (SAMM) and maternal
      mortality in the Pretoria region over a 2-year period (2000-2001). SETTING:
      Public hospitals in the Pretoria region, South Africa, serving a mainly indigent
      urban population. METHODS: A descriptive study was performed whereby women with
      SAMM and maternal deaths were identified at daily audit meetings and an audit
      form was completed for all cases fulfilling the definition of SAMM ('near miss')
      and for all maternal deaths. RESULTS: The number of maternal deaths declined
      slightly but not significantly from 18 deaths in 2000 to 16 in 2001. This
      represents a change in the maternal mortality ratio (MMR) from 130/100,000 live
      births in 2000 to a MMR of 100/100,000 live births in 2001. However, when data
      for women with SAMM and maternal deaths were combined, there was a significant
      increase in major maternal morbidity from 90 cases (SAMM and maternal death rate
      649/100,000 live births) in 2000 to 142 cases (SAMM and maternal death rate
      889/100,000 live births) in 2001 (p = 0.006). This increase was due to a
      significant increase in severe maternal morbidity related to abortions and
      obstetric haemorrhages. CONCLUSION: Analysis of maternal deaths only in the
      Pretoria region failed to identify abortions and haemorrhages as major maternal
      care problems. When data for women with SAMM were combined with data for maternal
      deaths, however, these problems were clearly identified, and remedial action
      could be taken. Including SAMM in maternal death audits increases the rapidity
      with which health system problems can be identified.

PMID- 14635561
TI  - [Modification of liver enzymes in undernourished rats treated with
      acetaminophen].
AB  - Acetaminophen is used as an analgesic and antipyretic. Due to its relative safety
      at therapeutic dose, it is frequently used in children and in pregnant women. We
      evaluated the effect of a dose equivalent to the therapeutic dose of
      Acetaminophen in undernourished rats; 72 Wistar male rats of 18 weeks of age,
      with weight between 270 and 280 g, were distributed randomly in four groups: A,
      normal without food restriction; B, normal without food restriction treated with
      Acetaminophen (100 mg/kg); C; undernourished by food restriction and D,
      undernourished by food restriction treated with Acetaminophen (100 mg/kg). The
      results showed decreasing of body and hepatic weight in undernourished rats and
      in undernourished treated with Acetaminophen, significant decrease of serum
      albumin concentration (p < 0.001). It was demonstrated that activity of the
      enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and
      alkaline phosphatase significantly decreased (p < 0.001) in the group of
      undernourished rats treated with Acetaminophen compared with the other groups. We
      concluded that the Acetaminophen induces hepatic lesions in undernourished rats
      treated with a single non toxic dose of 100 mg/kg of weight, probably as a
      consequence of the inherent susceptibility to malnutrition.

PMID- 14635562
TI  - [Use of UroLume as an alternative to the treatment of recurrent stenosis of
      bulbar urethra and obstructive prostatic hyperplasia in patients with high
      surgical risk].
AB  - This device consists of a woven in a form of a tubular mesh, made up for the use
      in the urethra. We report the clinical and uroflujometric results in 10 patients
      with urethral stricture and 4 with obstructive prostatic hyperplasia. The study
      includes a 7 year period since October of 1993 up until June 2000. All patients
      were evaluated pre and post stent insertion with periodic follow ups to assess
      the prostatic symptoms score, quality of life assessment, peak urinary flow rate,
      mean flow rate and post-void residual urine volume. The results were the
      following: For the group with urethral stricture the I-PSS decreased from 26.8 to
      5.4 points, the peak flow rate increased from 8.24 to 16.12 mL/sec and the post
      void residual urine volume decreased from 42.7 to 31.6 mL. By 12-month follow-up
      most endoprostheses were 90% covered with urothelium, only one of these patients
      required stent extraction with no sphincter lesion. For the prosthatic
      hyperplasia group the I-PSS decreased from 20.2 to 8 points. The peak flow rate
      increased from 6.95 to 14.5 mL/sec and the post-void residual urine volume
      decreased from 49 to 18.3 mL. By 12-month follow-up two patients were 95% covered
      with epithelium, and the other two were 70%. There have not been significant
      problems related to infections, migration, incontinence or erectile disfunction.
      An 80% of patients have shown some irritative symptoms (urgency, frequency or
      dysuria) at least during the first month after stent insertion. These 7 year
      results suggest that Urolume urethral endoprostheses can be a long-term effective
      treatment alternative to these patients.

PMID- 14635563
TI  - [Biopsy of sentinel lymph node in melanoma is not yet the standard treatment].
AB  - The trend to implement sentinel node biopsy as standard of care in patients with
      clinically localized melanoma is encouraged by the following three factors: the
      technique of lymphatic mapping has matured to the point that consensus was
      reached on how the procedure should be carried out, surgeons showed that they can
      find the node in nearly 100% of patients, and tumor-status was shown to be the
      most powerful prognostic factor. However, recent studies revealed unfavorable new
      information that questions the wisdom of this trend. Three studies published in
      2001 with a combined total of 1,851 patients show false-negative rates of 16-25%.
      Another unnerving finding is the 13-19% incidence of in-transit metastases in
      patients with a tumor-positive sentinel node, reported by three groups. The
      ultimate purpose of lymphatic mapping is to provide sentinel node positive
      patients with early therapeutic measures, such as regional node dissection and
      adjuvant systemic treatment. However, there is currently no evidence that this
      approach results in improved regional control and survival. Sentinel node biopsy
      can only become part of routine patient management if the tumor-status of the
      sentinel node carries clear implications of proven benefit for the manner in wich
      patients are managed and if regional control is not jeopardized.

PMID- 14635564
TI  - [Fractures in postmenopausal women in the IMSS: frequency and costs of hospital
      care].
AB  - OBJECTIVE: To analyze the frequency and costs of hospitalary care due to
      fractures in postmenopausal period occurred in Instituto Mexicano del Seguro
      Social (IMSS). MATERIAL AND METHOD: Study about hospitalary discharges in IMSS,
      among 2000-2001, with diagnosis of hip, distal forearm and vertebral fractures,
      with an analysis by sex and age groups. To estimate hospitalary costs, we
      utilized the data of Grupos Relacionados de Diagnostico (GRD) used in IMSS. The
      cost for each case was $46,965.30 mexican pesos ($5,101.63 U.S.D.). RESULTS: It
      were registered 22,157 (8.2%) were fractures of the selected types. Of this
      number, 15,925 ocurred in persons of 50 years and more y 11,084 (69.6%) in
      postmenopausal women. The mentioned fractures were more frequent in men before 50
      years with a proportion of 1.9 to 1. This proportion changed from 2 to 1 in women
      after 50 years. These differences were statistically significant. The cost of
      hospitalary care of hip fracture in postmenopausal women was $336,658.097 mexican
      pesos ($36' 593,271 U.S.D.) in the two years of the study. CONCLUSION: It is
      convenient to make costs-benefits evaluation about preventive resources, as
      widespread use of HRT, to reduce the frequency of fractures in postmenopausal
      women, due its high actual costs of hospitalary care.

PMID- 14635565
TI  - [Efficacy of decompression treatment of abdominal compartment syndrome].
AB  - INTRODUCTION: Abdominal compartment syndrome (ACS) is an entity that represents a
      latent problem in the patient subjected to laparotomy. OBJECTIVE: To evaluate the
      effectiveness of decompressive treatment of ACS. MATERIAL AND METHODS: We studied
      patients subjected to decompressive treatment for diagnosis of SCA from May 1 to
      November 30, 2001 prospectively. We evaluated intraabdominal pressure (IAP), peak
      pressure of air way (J)PVA), oxygen available index (OAi), ventilation-perfussion
      index and uresis, before, after, and at 48 h of decompressive surgery. The data
      were treated statistically with paired student t test taking as significant p <
      0.05 using percentages for qualitative variables and average with standard
      deviation for quantitative variables. RESULTS: We included 10 patients; three
      died (30%). Alone it VP & it descended significantly after compression (1 > <
      0.05). Uresis, PPVA, OlA and VPI were carried out 48 h of decompressive surgery.
      CONCLUSIONS: Decompressive treatment is effective in ACS, showing immediate
      decreased of IAP and improvement of the hemodynamic variables after 48 h post
      surgery.

PMID- 14635566
TI  - [Intestinal ischemia resulting from previous laparotomy].
AB  - INTRODUCTION: Acute adhesive obstruction of the small intestine is a surgical
      emergency in which there is a risk of intestinal ischemia. By delaying diagnosis
      and institution of appropriate treatment for ischemic obstruction, morbidity and
      mortality increase. MATERIAL, METHOD AND RESULTS: The hospital records of 63
      patients with diagnosis of intestinal obstruction and regional ischemia due to
      fibroadhesive peritonitis were reviewed in an attempt to identify criteria that
      could be used to separate patients who would require an emergency operation; 39
      (61.9%) were male and three (4.7%) newborn. This complication was seen after 3
      years of age in 39 patients (69.1%). Appendicitis was first cause with 26 cases
      (41.2%). Range of time of appearance after operation was from 1 week to 15 years
      (median 10 months). In 87% of patients the operation was a second procedure. All
      had gangrene and an enterostomy was constructed. General morbidity rate was 80%.
      Four children died. CONCLUSION: It is mandatory to identify which patients
      require non conservative management.

PMID- 14635567
TI  - [Tuberculosis: a current problem].
AB  - Tuberculosis is a public health problem. If the current trends continue, is
      expected to arrive to 10.2 million of new cases in 2005. There are three studies
      accomplished in 1995 in Mexican patients. The results show important difficulty
      in the application and the follow-up of the program of control of the
      tuberculosis, what has caused accumulation of chronic cases, moderate rate of
      primary resistance and alarming levels of primary and secondary multiresistance
      (23%). Mechanism of protective immunity against mycobacterium tuberculosis (MTB)
      in humans have not been clarified. Different subpopulations of lymphocytes CD4,
      CD8 and other populations as well as macrophages, and monocytes, have an
      important role. In industrialized countries, the managing of the MDRTB is based
      on the use of individualized treatments with second line drugs according to
      susceptibility test, however the foregoing has not been possible to apply it
      middle or low income countries. WHO has launches the initiative "DOTS plus" that
      consist in the administration of a standarized regimen on the basis of
      epidemiology of resistance in the country or region.

PMID- 14635568
TI  - [Caspases: apoptosis inducing molecules].
AB  - Caspases are key proteins for the transduction and ejection of the apoptotic
      signals induced by several stimuli. These proteins are present within the cell as
      inactive precursors that need a proteolytic cleavage in order to be active. There
      are two main caspases group, the initiators and executors. The formers are
      activated by autoproteolysis when translocated to specific cell compartments or
      trough the coupling of adapters and or activators. The executors caspases are
      activated by cleavage of an initiator caspase. These proteases are responsible
      then for the final cleavage of diverse substrates that mediate the morphologic
      changes during apoptosis. Among these there are signalization, DNA repairing,
      structure, transcription proteins, etc. Caspases represent a new paradigm in the
      signal transduction pathway, and are implicated in a large number of physiologic
      and pathologic processes. In a near future they could be useful pathologic
      markers and therapeutic targets.

PMID- 14635569
TI  - [A 41-year-old woman with hypercalcemia and bone lesions].

PMID- 14635570
TI  - [Mesenteric cyst as a cause of acute abdomen. Report of 3 cases].
AB  - Mesenteric cyst is a tumor of multiple origins that surely are found more
      frequently than the literature report, at any rate, this tumor is uncommon.
      Because of absence of characteristic clinical findings, diagnosis cumbersome,
      until these cysts are of such a size that palpation becomes possible or when they
      cause compression to nearby viscera. Occasionally, diagnosis is made during
      surgery, even when it was emergency surgery. The present paper reports on three
      patients with mesenteric cyst found during surgery as emergency treatment.
      Histopathologic reports showed lymphangioma in two cases and leiomyosarcoma in
      one case, quite uncommon in this kind of lesion.

PMID- 14635572
TI  - [On the origins of modern science].
AB  - The Renaissance savants essentially repelled the scholastic translations and
      commentaries of the ancient writings. Nevertheless, they did not reach a modern
      vision of experimental science. Moreover, education at the universities was not
      credited for the development of science. In fact, academic training of students
      was rather precarious. The first professional associations, such as the "Royal
      College of Physicians" of London, were not any better. Regarding the hermetic
      influence on Renaissance thought, the cultured and philosophical reformed magic
      (so-called white magic) was the equivalent of science at the time. Once the
      animistic universe, operated by magic, was transformed into the mathematical
      universe operated by mechanics, the era of science came into being. This movement
      began during the post-Renaissance age and gradually progressed following the
      physical-mathematical orientation of Galileo and his pupils: Borelli; Fabrizi;
      Santorio; Harvey, etc. They initiated physiological studies and introduced the
      quantitative method into the research field. Harvey's doctrine was the first
      adequate explanation of an organic phenomenon and a starting point for the way
      toward experimental physiology. However, the English physician did not completely
      leave the pre-scientific era, as can be inferred from his monography on animals
      reproduction. In this work, some points suggesting the birth of modern scientific
      reasoning alternate with confused, vague, and capricious assertions. In fact,
      modern science did not arise suddenly, but was elaborated and sustained slowly
      starting in the XVII century: Galileo's century.

PMID- 14635571
TI  - [Dermatomyositis and pregnancy].
AB  - INTRODUCTION: Dermatomyositis is a disorder known as a pathology whose etiology
      remains unknown. It can occur at any age with clinical symptoms of weakness and
      wasting, especially of the proximal musculature, due to inflammatory infiltration
      of muscles and destruction of muscle fibers. It is exceptionally seen during
      pregnancy, conditioning adverse effects in pregnant women. OBJECTIVE: The
      principal objective here is the presentation of a clinical case of
      dermatomyositis during pregnancy. CASE REPORT: Women of 33 years of age with term
      pregnancy, suffering from dermatomyositis from infancy, with satisfactory
      evolution. CONCLUSION: Dermitomyositis is a pathology of unknown origin whose
      incidence averages five cases in one million habitants with exceptional
      presentation during pregnancy. There are 29 case reports in the world literature.
      Perinatal morbimortality lies between 46 and 57% in case of activity. Fetal
      morbidity consists of intrauterine growth restriction prematurely and fetal
      death. Dermatomyositis has been associated with neoplasm LES and collagen
      disorders.

PMID- 14635573
TI  - [Medicine in the discovery of America].
AB  - The present manuscript aims to record some general aspects of science, and in
      particular from the beginning of anatomic studies, during the discovery of
      America. We mention by Vesalio, who was the best known anatomist of his time in
      the Western world. In addition this establishes the legal origins of the medical
      profession in Spain and America, with emphasis on distinct treatments, for
      example, those in Peru and Chile. This manuscript contains anecdotes and accounts
      of the time, the use of medicines of the day, and the relationship these had with
      the native medicine. Finally, medical department of Chile is described, together
      with a mention of the first hospitals of the Republic of Chile.

PMID- 14635574
TI  - [Pulmonary alveolar proteinosis, a cause of crazy paving pattern in high
      resolution computerized tomography].

PMID- 14635575
TI  - [Genes that influence aging].

PMID- 14635576
TI  - [In memory of Dr. Juan Maria Rodriguez Arangoiti, illustrious Mexican
      obstetrician (1828-1894)].

PMID- 14635577
TI  - Prescription Drug Abuse Task Force recommendations.

PMID- 14635578
TI  - Pediatric migraines: a case report.
AB  - Migraines are a common problem faced by the pediatrician. It can be difficult to
      determine the difference between a common headache and a migraine in young
      children. This case report will review a case that presented to the neurologist's
      office, then discuss the epidemiology, pathophysiology, classification of
      migraine, migraine variants, clinical evaluation, differential diagnosis, and
      treatment of migraines in a pediatric population.

PMID- 14635579
TI  - Bilateral abducens nerve palsy from mild trauma with force applied at an oblique
      angle: a case report and review of the literature.
AB  - Traumatic bilateral abducens nerve palsy is rare. Bilateral palsy due to a force
      applied at an angle is even more unusual. We report a case of bilateral traumatic
      abducens nerve palsy without fracture after striking the right side of the face
      in a fall. The palsy did not improve after several months and the patient
      underwent successful corrective surgery. The literature on bilateral traumatic
      abducens nerve palsy is reviewed. Possible mechanisms are discussed, as well as a
      possible mechanism for traumatic bilateral abducens nerve palsy with force
      applied at an angle.

PMID- 14635581
TI  - Aunt Irene.

PMID- 14635580
TI  - Prevalence of prescription drug abuse and dependency in patients with chronic
      pain in western Kentucky.

PMID- 14635583
TI  - [Risk factors of cardiovascular disease among young adults].
AB  - BACKGROUND: A precise knowledge of the prevalence and importance of
      cardiovascular risk factors will facilitate the development of preventive
      strategies. AIM: To study cardiovascular risk factors among healthy young adults.
      SUBJECTS AND METHODS: Eight hundred and fifty subjects aged 22 to 28 years,
      living in two cities in Valparaiso province, were studied. Weight, height and
      blood pressure were recorded. A fasting blood sample was obtained from 806
      individuals (54% female), to measure plasma lipids, glucose and insulin levels,
      to estimate their homeostasis model assessment scores (HOMA) and to evaluate the
      occurrence of metabolic syndrome. RESULTS: Five percent of the studied population
      had high blood pressure, 14% had obesity, 57% smoked, 25% had high total
      cholesterol levels, 10.5% had high levels of low density lipoprotein cholesterol,
      46% had low levels of high density lipoprotein cholesterol, 16% had high
      triglyceride levels, 36% had insulin resistance, 7% had a metabolic syndrome, 14%
      were heavy drinkers and 38% were sedentary. Women had a higher prevalence of
      obesity and metabolic syndrome. In only 24% of the studied subjects, no risk
      factor was identified. CONCLUSIONS: A high prevalence of cardiovascular risk
      factors was found in this population of young adults.

PMID- 14635582
TI  - [Detection of malignancy markers in thyroid nodules by reverse transcriptase
      polymerase chain reaction (RT-PCR)].
AB  - BACKGROUND: Nodular thyroid disease is a very common disorder with a low
      frequency of malignancy. The most accurate diagnostic test is fine needle
      aspiration biopsy (FNAB) of nodules with cytological analysis of the sample.
      However, this procedure has some limitations in the diagnosis of follicular and
      papillary thyroid carcinoma. AIM: To detect mRNA from specific malignancy markers
      in thyroid nodules and to evaluate their potential correlation with cytological
      and pathological diagnosis. PATIENTS AND METHODS: In 20 patients with thyroid
      nodules FNAB was performed prior to surgery. The main part of the FNAB sample was
      used to perform classical cytology. In the remaining of the sample were detected
      MUC-1, CD26, galectin-3 and TSH receptor mRNAs by RT-PCR technique. RESULTS:
      Eight patients had positive cytology for papillary cancer, which was confirmed by
      pathology. Nine had suspicious or non conclusive cytological findings and 3 were
      negative for neoplastic cells; all 12 were pathologically benign. We detected TSH
      receptor and galectin-3 mRNA in almost all benign and malignant nodules. MUC-1
      was present in 5/8 papillary carcinoma (62.5%), and 1/12 benign nodules (8.3%).
      CD26 was detected in 7/8 papillary carcinomas but also in 8/12 benign nodules.
      CONCLUSIONS: RT-PCR can be performed in very small samples of thyroid tissue to
      detect several mRNA markers. MUC-1 can be a potentially useful marker of
      malignancy in thyroid nodules. It can be detected by RT-PCR as a complementary
      technique in the diagnostic evaluation of thyroid nodules.

PMID- 14635584
TI  - [Abdominal aortic aneurysms in patients over 80 years of age: conventional
      surgical treatment in 80 consecutive cases].
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) may be lethal unless appropriately
      and timely treated. Since age is a surgical risk, octogenarians are usually not
      considered as candidates for surgical intervention. AIM: To asses surgical
      complications and mortality in octogenarians treated for AAA. SUBJECTS AND
      METHODS: Patients aged 80 years older, treated consecutively between 1984-2001
      were retrospectively analyzed. RESULTS: Sixty one patients were male, and their
      age ranged from 80 to 95 years. All were treated with open surgery. The operation
      was elective in 58 and as an emergency in 22 patients (symptomatic or ruptured
      AAA). Aortic diameter was 6.8 +/- 1.4 cm in asymptomatic patients and 7.7 +/- 1.8
      cm in emergency cases (p = 0.024). Thirty days postoperative mortality was 5.1%
      in elective surgery compared to 40.6% in emergency operations (p < 0.01). Five
      years survival rate was 44.7% in asymptomatic patients compared to 10.4% in the
      emergency cases (p < 0.023). CONCLUSIONS: Elective surgery for asymptomatic AAA
      can be performed with low operative mortality in octogenarians. However, surgery
      in emergency cases has an 8 fold increase in risk. Accordingly, octogenarian
      patients should be considered for elective AAA repair in a selective basis.

PMID- 14635585
TI  - [Neighborhood effects influencing reproductive health of Chilean women].
AB  - BACKGROUND: Fecundity rates have decreased considerably in Latin America, due to
      a higher contraceptive use and better family planning programs. AIM: To determine
      whether neighborhood level socioeconomic variables have an independent effect on
      reported modern contraceptive use, over and above the effect of individual level
      measures of socioeconomic status and reproductive health behavior. SUBJECTS AND
      METHODS: Multilevel logistic models determined the effects of individual and
      neighborhood dimensions (socioeconomic status, urbanization, quality of public
      health facilities) on contraceptive use among 509 women aged 15 to 49 years
      living in 85 neighborhoods within the Region of Bio Bio, Chile. RESULTS: After
      adjustment for women's individual socioeconomic characteristics and other risk
      factors, less favorable neighborhood socioeconomic characteristics were
      significantly associated with lower rates of modern contraceptive use.
      CONCLUSIONS: Changes in the quality of facilities for family planning at the
      neighborhood level may enhance modern contraceptive use.

PMID- 14635586
TI  - [Serum homocysteine in children and adolescents. Relation with family history of
      cardiovascular disease].
AB  - BACKGROUND: Hyperhomocysteinemia is an independent cardiovascular risk factor
      that depends on folate and vitamin B12 nutrition. AIM: To measure homocysteine,
      folic acid and vitamin B12 serum levels in healthy children with and without a
      family history of cardiovascular disease. SUBJECTS AND METHODS: Forty children
      aged 6 to 15 years with a family history of cardiovascular disease, and 40 age
      and sex matched children without such history were studied. Serum homocysteine,
      folic acid and vitamin B12 were measured in a fasting blood sample. Homocysteine
      was measured by a fluorescence polarization immunoassay (FPIA), vitamin B12 by
      enzymatic microparticle assay, covered with intrinsic factor and folic acid by
      ionic capture, using commercial kits. RESULTS: Children with family history of
      cardiovascular disease had higher homocysteine levels than their counterparts
      without family history (7.9 +/- 3 and 5.8 +/- 2 mumol/l respectively, p < 0.03),
      but similar folic acid (5.2 +/- 1.8 and 5.5 +/- 1.4 pg/ml respectively) and
      vitamin B12 levels (431 +/- 213 and 445 +/- 209 ng/ml respectively). There was a
      negative and significant correlation between homocysteine and folic acid and
      vitamin B12 levels. CONCLUSIONS: Children with a family history of cardiovascular
      disease have higher levels of serum homocysteine than those without such history,
      despite having similar levels of folic acid and vitamin B12.

PMID- 14635587
TI  - [Seroepidemiology of toxoplasmosis in a Yucpa Amerindian community of Sierra de
      Perija, Zulia State, Venezuela].
AB  - BACKGROUND: There is a high rate of Toxoplasma gondii infection worldwide. In
      Latin America the rate is as high as 65% in some populations. AIM: To measure the
      prevalence of antibodies against Toxoplasma gondii in a native Yucpa community in
      Venezuela. SUBJECTS AND METHOD: Total serum antibodies measured by indirect
      hemagglutination and IgM antibodies by ELISA were measured in 94 Yucpa subjects
      (49 males), aged from 3 months to 100 years. RESULTS: The overall prevalence of
      infection was 63%. Fifty nine subjects had total antibodies and 14 had IgM
      antibodies. No significant differences by age or sex, were observed in the
      proportion of subjects with positive total or IgM antibodies. CONCLUSIONS: The
      studied individuals had a high prevalence of Toxoplasma gondii infection.

PMID- 14635588
TI  - [Association between sunburn in children and ultraviolet radiation and ozone
      layer, during six summers (1996-2001) in Santiago, Chile (33,5 degrees S)].
AB  - BACKGROUND: During the recent 10 years the ozone layer has decreased while
      ultraviolet radiation has increased in Santiago, Chile. AIM: To determine whether
      the number of sunburns in children correlate with ultraviolet radiation in
      Santiago. SUBJECTS AND METHODS: During six Austral Summers (1996-2001) children
      below 15 years old, consulting for sunburn, were evaluated at the "Corporation
      for the Aid of Burned Children" (COANIQUEM) in Santiago (33.5 degrees S). The
      number of children with sunburns during each Summer was compared with the
      corresponding UV-B radiation and the ozone thickness, to establish a probable
      relation between a geophysical change and its consequences in skin health. The
      ozone layer values were obtained from the NASA WEB-page and the ultraviolet
      radiation was measured with a four-channel medium resolution radiometer. RESULTS:
      In each Summer there was a predominance of sunburns among boys and among ages
      between 6 and 10 years. During the 96-97 Austral Summer, the highest number of
      children with sunburns (63) was diagnosed. That Summer also had the highest mean
      UV-305 nm radiation with an important amount of days with ozone < or = 260 Dobson
      Units. Only during that Summer an inverse correlation between ozone and UV-305 nm
      radiation was detected. At the same time the maximal values of Erythemal Dose
      Rate (33 muWatt cm2), UV Index (13) and Erythemal Daily Dose (7.500 Joule m2)
      were observed. CONCLUSIONS: In Santiago, Summers with a higher number of days
      with low ozone protection seem to reappear every 3 years. Understanding the
      interaction of physical processes that control the ozone layer, may help to
      design better photo-protection programs for human health.

PMID- 14635589
TI  - [High risk febrile neutropenia in acute leukemia. The experience of a public
      hospital. National Program of Antineoplastic Drugs in Adult, Hospital del
      Salvador, 1991-2001].
AB  - BACKGROUND: Febrile neutropenia is one of the most important problems to face
      during the treatment of acute leukemia. AIM: To assess the results of a
      standardized protocol for the treatment of febrile neutropenia and compare it
      with a period in which treatment was not standardized. PATIENTS AND METHODS: One
      hundred and eight episodes of febrile neutropenia in 69 patients, treated with a
      standardized antimicrobial protocol between 1996 and 2001, were analyzed. The
      protocol consisted in the use of a combination of antimicrobial whose spectrum
      was broadened progressively according to the isolated microorganisms and the
      involved foci. These were compared with 83 episodes in 54 patients, treated
      without standardized protocols between 1990 and 1995. RESULTS: Both groups of
      patients were comparable. Their ages ranged from 15 to 65 years old. The
      male/female ratio was 1.3 and the lymphoblastic/myeloid leukemia ratio was 1.4.
      Sixty one percent of episodes occurred during induction chemotherapy and mean
      duration of neutropenia was 17 days. A clinically significant focus was
      identified in 72% of episodes and a microorganism was isolated blood culture in
      35% of them. There was a predominance of gram negative organisms. The mortality
      decreased from 18 to 9% in the period 1996-2000 (p = 0.094). CONCLUSIONS: The use
      of a standardized antimicrobial protocol reduced the mortality in febrile
      neutropenia, even when colony stimulating factors and filtered air rooms are
      unavailable.

PMID- 14635590
TI  - [Admission diagnosis and nutritional evolution of the beneficiaries of
      "Corporacion para la Nutricion Infantil-CONIN"].
AB  - BACKGROUND: The nutritional impact of CONIN nutritional recovery centers must be
      evaluated, considering the current epidemiological situation in Chile and the new
      therapeutic focus giving more emphasis to ambulatory treatment. AIM: To analyze
      the nutritional status of children treated at traditional CONIN centers, the
      reason for their admission and the factors associated with changes of weight for
      age index during the hospitalization. PATIENTS AND METHODS: During the year 2000,
      the records of 561 patients discharged from the traditional CONIN centers
      throughout the country were retrospectively analyzed. The changes in weight and
      height during admission and the possible factors influencing these changes, were
      determined. RESULTS: The average lapse of stay was 3.9 months; 78% of children
      had concomitant diseases at admission and 18.7% required to be admitted in a
      general hospital. One third was admitted with normal weight or even overweight
      according to the weight for age index, and 31.1% was undernourished. During
      admission in CONIN, the number of undernourished patients was reduced by 50%,
      while the proportion of children with normal nutritional status increased by 15%
      (p < 0.001). On admission, 7.8% of children had a low height for age, evidencing
      a chronic undernutrition. This figure did not change on discharge. The increase
      of weight/age and weight/height was substantially higher in children with a
      greater initial deficit (p < 0.001). CONCLUSIONS: Admission to a CONIN center had
      a low nutritional impact, and a high risk of a lengthy stay. The most favorable
      impact could be appreciated in children that were effectively undernourished.
      Admissions are motivated mainly by social issues, over and above nutritional
      problems.

PMID- 14635591
TI  - [Catastrophic antiphospholipid syndrome and acute heart failure. Report of a
      case].
AB  - A 33 years old woman was admitted to the hospital after four days with cough,
      dyspnea, orthopnea and hemoptysis. Blood pressure was 170/90 mmHg, pulse was 112
      and temperature was normal. She had cyanosis and a left ventricular gallop,
      without heart murmurs. A chest radiograph revealed pulmonary edema and
      echocardiogram showed a global left ventricular systolic disfunction. Oxygen and
      furosemide were started, but cardiopulmonary collapse ensued. The patient was
      supported with mechanical ventilation and treated with inotropic drugs. A right
      sided cardiac catheterization showed pulmonary wedge pressure of 18 mmHg and a
      cardiac index of 3 l/min/m2. The levels of creatinine and urea nitrogen were
      elevated and a urine protein was 97 mg/dl. Coagulation tests were normal except
      by a positive lupic anticoagulant. Markers of connective tissue diseases or
      vasculitis were negatives. The clinical evolution suggested that a catastrophic
      antiphospholipid syndrome was ongoing. Intravenous corticoids, gammaglobulin and
      cyclophosphamide were administered with transient improvement. On her fourth day
      of treatment, the patient presented sudden pulmonary bleeding and embolism. A
      plasmapheresis was performed with improvement of renal, cardiac and pulmonary
      function. After this episode, the patient has been treated with prednisone and
      oral anticoagulants treatment for the last two years, without further clinical
      events.

PMID- 14635592
TI  - [Blindness caused by an ischemic optic neuropathy by spontaneous carotid
      dissection. Report of a case].
AB  - In young and middle age subjects, spontaneous carotid dissection is an
      increasingly recognized cause of ischemic stroke. Their usual presentation is
      facial pain with a Horner syndrome and a contra lateral paresis. Blindness has
      been reported as a presenting symptom in only a few cases. We report a 50 years
      old man who presented with amblyopia in the left eye, without periocular pain.
      Fundoscopy showed papilledema and a peripapillar hemorrhage, compatible with an
      ischemic optic neuropathy. A magnetic resonance angiography confirmed a left
      carotid dissection.

PMID- 14635593
TI  - [Non convulsive status epilepticus: an heterogeneous disease with a difficult
      diagnosis. Report of 2 cases with unusual presentation].
AB  - Non convulsive status epilepticus is a heterogeneous condition consisting of very
      different electroclinical syndromes. It is difficult to make the diagnosis and
      identify common factors among patients. We report two cases with an unusual
      presentation. A 31 years old woman having discoid lupus presented with a
      prolonged exogenous psychosis that lasted two and half months, associated to
      echolalia. After the episode the patient remained with a severe frontal syndrome
      that could be the consequence of a non convulsive status epilepticus. A 60 years
      old woman with an epilepsy diagnosed at the age of 30, presented with recurrent
      episodes of aphasia. During one of these crises, the electroencephalogram showed
      continuous epileptiform activity.

PMID- 14635594
TI  - [Delirium: the clinical confusion].
AB  - Delirium or acute confusional state is a condition that lies within the
      boundaries of psychiatry and other medical specialties. It is defined as a
      syndrome characterized by a fluctuating cognitive impairment of acute onset. The
      pathogenesis is multifactorial and it frequently appears in elderly patients
      admitted to general hospitals. Delirium carries a high mortality and it prolongs
      hospital stay. Its diagnosis if often overlooked and the treatment is inadequate
      or belated. This article discusses the most efficient procedures to diagnose and
      treat delirium. The review was based on a systematic search in the literature
      using the key words delirium, acute mental syndrome, acute confusional state and
      organic mental syndrome. Articles were selected according to their relevance and
      methodological accuracy.

PMID- 14635595
TI  - [Intercultural health: elements to the construction of its conceptual bases].
AB  - Over the past few years, intercultural health has become an emerging issue in
      health policy. Intercultural health is an approach to create a better
      communication between patients and providers. In the short term, this approach
      incorporates patient's culture background in health care, improving intercultural
      communication strategies to generate, in the long term, a health system adapted
      to the medical culture of patients. This article explores the underlying concepts
      in the intercultural health approach, such as cultural diversity and medical
      systems as complex models of thoughts and behaviors.

PMID- 14635596
TI  - [Psychological types and learning styles of students entering medical school at
      the Pontificia Universidad Catolica de Chile].
AB  - BACKGROUND: Psychological type and learning style influence the way students
      perceive and process information. However, research in medical education in Chile
      still does not put enough emphasis in the study of these variables. AIM: To
      characterize the psychological types and learning styles of the students admitted
      to a Medical School. SUBJECTS AND METHODS: The Myers Briggs Type Indicator (MBTI)
      and the Kolb's Learning Styles Inventory (IEA) were administered to the 270
      students admitted from 2000 to 2002 to the medical school of the Pontificia
      Universidad Catolica de Chile. RESULTS: Fifty five percent of our students are
      concentrated in 4 of the 16 psychological types described. These students are
      characterized by the ability to base their decisions upon logical and objective
      reasoning (Thinking [T]) and to face life in a structured and decided way
      (Judging [J]). Only 10% of the students have preferences opposite to T and J.
      These students base their decisions on the preservation of harmony and teamwork
      (Feeling [F]) and have a flexible attitude towards life (Perceiving [P]). The
      remaining 35% have types with pairs of preferences TP and FJ. With regard to
      learning styles, more than two thirds of our students are Assimilators or
      Convergers. These learners tend to assimilate large amounts of information and
      abstract the main concepts, rather than to pay attention to concrete details. In
      general, our students are more reflective than active; they evaluate thoroughly
      all alternatives before making a decision. CONCLUSIONS: The psychological types
      and learning styles of medical students cluster around specific patterns whose
      features may either favor or hamper a specific learning. Knowledge of the
      differences in psychological types and learning styles of students may provide
      teachers with a new and valuable tool for improving learning and contributing to
      the academic success of students.

PMID- 14635597
TI  - [Bioethical aspects of the Health Care Reform in Chile. The problems of access
      and costs of resources ].
AB  - During the process of health reforms there is always the concern that patients
      rights might be harmed. The bill that is being discussed in the Chilean
      Parliament contains an special issue dedicated to patient's obligations and
      rights. However, on the author's opinion, the best protection for patient rights
      rests on adequate financing and access to a reasonably, good and qualified health
      care. A thorough revision of the proposals contained in the reform will allow an
      objective assessment of the eventual ethical problems that it might imply.

PMID- 14635598
TI  - Eosinophilic pneumonia caused by mesalazine. Report of one case.

PMID- 14635599
TI  - [Nifurtimox treatment of chronic Chagasic infection in children].

PMID- 14635600
TI  - [Celebrating science, teaching, and life. The legacy of Arthur C. Guyton].

PMID- 14635601
TI  - [Cavernous angioma. Clinical observations and prognosis of 133 patients].
AB  - BACKGROUND: Cavernous angiomas represent 9% of the vascular malformations that
      affect nervous system. The principal mode of onset is cerebral hemorrhage and
      epilepsy, and can be sporadic of multiple. In the last, there is a familiar
      factor specially found in Mexician-American. In our Country there is no data of
      the clinical or demographic characteristics of the disease. The aim of this study
      is to describe the clinical characteristics and prognosis of 133 patients with
      cavernous angiomas consecutively attended in the National Institute of Neurology
      of Mexico City. PATIENTS AND METHODS: Since 1988 we evaluated a total of 146
      cases of cavernous angiomas, 133 were confirmed by MRI and included in the
      analysis of this study. In every case we registered the demographic
      characteristic, neurological manifestations, and prognosis divided in good o bad
      outcome, according to the Glasgow outcome scale (1 and > or = 2 respectively).
      Data were analyzed with descriptive statistics with the Chi square test, and p
      was set at 0.05 level. RESULTS: The mean age was 34.3 +/- 14.6 years; 50.4% in
      male. Eighty seven percent were unique, and the principal manifestation was
      supratentorial in 65%, infratentorial in 24.8%, supra-infratentorial in 6.8%, and
      spinal in 3.8%. The clinical manifestations were intracerebral hemorrhage in
      58.7%, epilepsy in 48.1%, headache in 37.6%, neurological focalization not
      secondary to hemorrhage in 8.3%, and incidental in 2.3%. The 6 month outcome was
      good in 80% of patient assessed by the Glasgow outcome scale. CONCLUSIONS: In our
      serie the mean age or presentation was 34 years old, the mean neurological
      manifestations were cerebral hemorrhage and epilepsy, and the outcome was good in
      the majority of the cases.

PMID- 14635602
TI  - [Survival at 5 years of adult patients with acute lymphoblastic leukemia].
AB  - OBJECTIVE: To estimate and to compare against other series, the overall survival
      time (OST) in patients with diagnosis of acute lymphoblastic leukemia (ALL),
      cared for and followed-up at a tertiary-care hospital in Merida, Yucatan, Mexico,
      between January 1995 to December 1999. MATERIAL AND METHODS: Clinical records of
      110 patients aged 14 years or older, were identified and reviewed. Age, sex, ALL
      subtypes, follow-up time, OST and mortality rates were the analyzed variables.
      Inferential statistics, including parametric and nonparametric tests and its 95%
      confidence intervals (95% CI), were used when appropriate. Six months periods,
      the median survival time (MST), and the five-years OST using Kaplan-Meier methods
      (K-M) for ALL as a group and for its subtypes, were calculated. RESULTS: The
      median age of ALL patients was 19 years. Male gender was more affected (68%) than
      female gender. One to 55 months was the followed-up time, being the followed-up
      mean time 16.9 +/- 12.1 months, although 12 months, 55 months and sixty months
      OST was 70%, 11% and zero percent, respectively, being during all the followed-up
      time always unfavourable to male gender. Mortality rate was 53%, and male was
      again the most affected one. L2-ALL was the most frequent subtype, having the
      least mortality rate (38%) between subtypes (p = 0.012) because its OST was
      better than for L1 and L3 subtypes. CONCLUSIONS: In ALL adult patients, mortality
      rate was higher having 0% OST, at 60 months.

PMID- 14635603
TI  - [Prevalence of psychiatric disorders in patients with severe obesity waiting for
      bariatric surgery].
AB  - INTRODUCTION: Obesity is a chronic condition, in which different systems of the
      body are affected. There are some previous studies in which the prevalence of
      psychiatric disorders in extreme obese patients has been reported, but there are
      some methodological problems. As far as we know this is the first report of the
      prevalence of psychiatric disorders in obese patients that need to have a
      surgical treatment for this disorder in Mexico. The main goal of this study was
      to determine the prevalence and risk factors of psychiatric disorders in extreme
      obese patients candidates to bariatric surgery. MATERIAL AND METHODS: The
      Structured Clinical Interview for DSM-IV (SCID) axis I disorders, were performed
      in 70 obese patients that will undergo for bariatric surgery. Also the medical
      files were reviewed in order to obtain the main medical conditions related to
      obesity. RESULTS: There were 25 men and 35 women in this study (average age +/-
      s.d = 39.0 +/- 10.4). The Body Mass Index (BMI) was 53.8 +/- 11.9. Sixty percent
      of the patients had some psychiatric disorder in the axis I of DSM-IV. The most
      frequent psychiatric problem that was observed was anxiety disorders. The main
      medical problems observed were: arterial hypertension (59%), diabetes mellitus
      type 2 (29%) and obstructive sleep apnea syndrome (29%). The BMI and diabetes
      mellitus were associated with a lower risk for presenting a psychiatric disorder
      (for a BMI of 65.5 +/- 10.3 kg/m2: OR 0.26, CI 0.05-1.15, p = 0.04; for diabetes
      mellitus: OR 0.20, CI 0.03-1.05, p = 0.02). CONCLUSIONS: More than half of the
      patients had at least one psychiatric disorder in axis 1 of DSM-IV, related
      mostly to anxiety and mood disorders. Our findings point out the importance of
      psychiatric and psychological intervention in this group of patients, in which a
      follow up and adherence of medical, nutritional and psychological problems could
      be the difference, between a good or bad prognosis. Follow-up studies with obese
      patients after bariatric surgery, will be important to support our findings.

PMID- 14635604
TI  - [Usefulness of lymphatic mapping with sub-areolar injection of patent blue dye,
      in the typification of breast cancer].
AB  - INTRODUCTION: Although the axillary radical dissection continues being the
      standard treatment for patient with breast cancer, the lymphatic mapping with
      biopsy of the sentinel node has arisen as a possibility to appropriately staging
      patients without palpable axillary nodes (NO) and to prevent axillary
      lymphadenectomy. The best method to perform it is with the association of
      radiocolloid and dye, nevertheless for this purpose an intraoperatively gamma
      probe is needed, when is not possible to get it, the procedure must be done only
      with dye, therefore is important to select the most successful administration way
      for the sentinel node (SN) identification. OBJECTIVE: To show that the lymphatic
      mapping with subareolar injection of blue dye has a high success rate for
      lymphatic mapping in breast cancer patients. MATERIAL AND METHODS: Lymphatic
      mapping was practiced to 62 breast cancer patients with subareolar injection of
      blue dye. All the patients were subject to axillary dissection, the index of
      false negatives, sensitivity and negative predictive values were estimated. The
      need to perform the mapping with association of radiocolloid--dye was assessed
      according to the literature. RESULT: The SN was identified in 58 patients (93.5%
      success rate), the index of false negatives was of 5.2% with sensitivity of 93%
      and the negative predictive value was of 97.5%. CONCLUSIONS: The SN is a
      predictor of the axillary node state, the subareolar dye injection technique has
      a high success rate in the identification of the sentinel node.

PMID- 14635605
TI  - [Reliability of CA 15-3 in the follow up of female patients with breast carcinoma
      and bone metastases].
AB  - The breast cancer is one of the most frequent in the world, with an incidence
      that has been raising despite the many different prevention programs. In the
      early 1980s, two groups of investigators report a new tumor marker and called it
      cancer antigen 15-3 (CA 15-3). CA 15-3 in the diagnostic and follow up of
      patients with breast cancer has a sensitivity ranging from 75-76.9% and the
      specificity ranging from 85.5-93%. METHODS: We review the files of 100 female
      patients in the Nuclear Medicine Department, which was done bone scan and CA 15-3
      from January to December 2000. All patients were in stage III and IV. For the
      bone scan every patient received 20 mCi of Medroxi-Di Phosphonate (MDP). The CA
      15-3 was quantify in the radioimmunoanalysis (RIA) laboratory. The CA 15-3
      reference protocol is equal or less than 30 U/mL. RESULTS: The mean patient's age
      was 59.39 years. The mean value from CA 15-3 for the patients with the absence of
      metastatic disease is 16.18 U/mL and 164.02 U/mL in the presence of metastatic
      disease mL (p < 0.00001). In our research the high level was 35 U/mL (percentil
      95). The sensitivity founded was 82% and the specificity was 87%. High CA 15-3
      levels are present when the patient has the tumor and get down to normal when the
      tumorectomy of the mastectomy was done; in the absence of metastatic disease.
      CONCLUSIONS: Skeletal scintigraphy is reserved for patients with clinical stage
      III and IV disease. Image those patients who have skeletal pain or high levels of
      CA 15-3 although an early stage disease. In patients with skeletal metastases and
      chemotherapy protocol there is a significative diminish of the value of the tumor
      marker in comparison with the previous one. In patients with metastatic disease
      and normal CA 15-3, the tumor marker will increase gradually. CA 15-3 can be use
      as a simple method that reflects the presence of bone metastases in association
      with bone scan.

PMID- 14635606
TI  - Comparison of several formulas to assess insulin action in the fasting state with
      the hyperglycemic-hyperinsulinemic clamp technique in healthy individuals.
AB  - BACKGROUND: The aim of this study was to correlate several formulas to assess
      insulin action in the fasting state with the hyperglycemic-hyperinsulinemic clamp
      method in healthy individuals. METHODS: A cross-sectional study was carried out
      in 33 healthy, non-obese volunteers. A hyperglycemic-hyperinsulinemic clamp
      technique was performed and the following formulas to assess insulin action in
      the fasting state were calculated: reciprocal insulin, glucose to insulin ratio,
      homeostasis model analysis, Raynaud index, Belfiore index, reciprocal of fasting
      insulin resistance index and quantitative insulin sensitivity check index.
      Pearson correlation was used to correlate the above mentioned formulas with the
      clamp method. RESULTS: There were significant correlations between results of the
      several formulas and those obtained with the clamp technique. The reciprocal of
      insulin index had better correlation with the clamp method. CONCLUSIONS: All
      formulas evaluated to assess insulin action in the fasting state had a
      significant correlation with the hyperglycemic clamp technique.

PMID- 14635607
TI  - HLA CW3 and HLA CW4 have a protective effect on acquisition of chronic myeloid
      leukemia on Mexican patients.
AB  - INTRODUCTION: Chronic myeloid leukemia (CML) is characterized by a chromosomal
      translocation t(9; 22) resulting in the chimeric ber-abl oncogene that encode for
      the p210 protein which has an increased tyrosine kinase activity. The fusion part
      of this protein contains a novel aminoacid sequence. If peptides derived from
      this leukemia-specific part of p210 are expressed in the context of HLA molecules
      on malignant cells this may elicit immunologically specific responses. Recent
      studies using synthetic peptides identical to the bcr-abl fusion region revealed
      that breakpoint specific peptides are capable of binding to the class I molecules
      HLA-A3, -A11 and -B8. It has been shown that individuals expressing HLA-A3 or HLA
      B8 have a diminished risk for development of CML in Caucasoid populations. Other
      authors have reported a statistically significant increase in the frequency of
      Cw3 and Cw4 antigens in Causcasoids and European CML patients. These data
      suggested that Cw3 and Cw4 may be markers for CML susceptibility on these
      populations. OBJECTIVE: To asses a possible susceptibility effect of these HLA
      molecules we studied 63 CML Mexican Mestizo patients and 746 healthy subjects for
      the distribution of HLA class I and class II molecules. RESULTS: The gene
      products that showed statistically significant differences between CML patients
      and controls were DR14, DR3, Cw3 and Cw4. DR14 and DR3 were significantly
      increased in the patients group with respect to the controls group (DR14 antigen
      frequency: 3.17% vs. 0.29%; p = 0.03; DR3 20.63% vs. 8.33%; p = 0.0001). Cw3 and
      Cw4 were significantly decreased in the patient group (Cw3 26.9% vs. 49.11%; p =
      0.03; Cw4 antigen frequency 23.8% vs. 86.28%; p = 0.0000001). The relative risk
      for DR14 was 10.48 (95% CI 1.52-79.29) and for DR3 was 3.96 (95% CI 2.05-7.71).
      The relative risk for Cw3 was 0.38 (95% CI 0.08-1.79) and for Cw4 was 0.11 (95%
      CI 0.048-0.81). CONCLUSION: These results suggest that the development of CML is
      apparently associated with HLA phenotypes specific to each population, and
      indicate that Cw3 and Cw4 expression may result in a protective effect on the CML
      acquisition on Mexican Mestizo population probably by bcr-abl breakpoint peptides
      presentation through these HLA molecules.

PMID- 14635609
TI  - Variations of vital signs, skin color, behavior and oxygen saturation in
      premature neonates after sponge bathing. Possible complications.
AB  - BACKGROUND: Although sponge bathing is a routine practice in preterm newborn
      infants, there is evidence suggesting that this procedure is not always
      innocuous. The objective of this study was to determine whether the sponge bath
      induces significant changes in vital signs, skin coloration, behavior and
      peripheral oxygen saturation in the non-critically ill preterm newborn infants,
      and to assess possible complications. MATERIAL AND METHODS: Seventy nine preterm
      neonates were prospectively studied between August and November 1999. Vital
      signs, peripheral blood oxygen saturation, skin color and behavior (according to
      Prechtl) were assessed 10 minutes before and 10 minutes after a sponge bath. Data
      were analyzed by descriptive and inferential statistics, using paired Student's t
      test, Wilcoxon's rank sum test or McNemar's test when pertinent. Statistical
      significance was considered when p < 0.05. RESULTS: Vital signs, skin color,
      behavior and peripheral oxygen saturation all changed significantly after the
      sponge bath (p < 0.01). No complications were observed within 24 hours after the
      procedure. CONCLUSIONS: The vital signs, skin color, behavior and oxygen
      saturation of non-critically ill preterm newborns changed significantly after
      sponge bathing, although no complications were observed. However, because of
      these physiologic changes we consider that sponge baths should be performed as
      quickly as possible in preterm newborn infants.

PMID- 14635608
TI  - [Influence on white coat effect and heart rate of antihypertensive agents used at
      a urban health center].
AB  - BACKGROUND: We name white coat effect (WCE) to the difference between the
      systolic arterial pressure (SAP)/diastolic AP (DAP) of consulting room and the
      ambulatory obtained one with ambulatory blood pressure monitoring (ABPM). In our
      work we analyzed by means of ABPM, the influence of the antihypertensive
      medicaments on the WCE and the cardiac frequency of use of the antihypertensive
      ones. DESIGN: Almost experimental study (with a period before and a period later)
      and descriptive. SETTING: Primary care. Urban health centre. PARTICIPANTS AND
      MAIN MEASUREMENTS: Studies of ABPM were realized to 70 hypertense essential
      patients with good control of the arterial pressure after pharmacological
      treatment before suspending the antihypertensive medication (phase 1) and to the
      4 weeks of leaving the treatment (phase 2). RESULT: Or all 70 hypertense
      patients. 18 (26%) did not manage to carry out the second ABPM (unbalanced during
      the wash) that forced to re-introduce the antihypertensive medicaments. The WCE
      systolic and diastolic is significantly more raised in patient males in treatment
      with diuretics with regard to which they use other pharmacological groups. The CF
      is significantly more raised in patient women who do not take blockaders thread
      (they use another group) with regard to they take it. In the blockaders alpha the
      CF is significantly more raised in the women who use it with regard to that they
      use antihypertensive other one. Of all 52 patients who were realized double ABPM,
      WCE was significantly top in phase 1 that in 2. CONCLUSION: In hypertense
      controlled patients, the diuretics (in males) are the pharmacological group that
      of more significant way influences on WCE, them raising with regard to the
      patients who take antihypertensive other one, being in influence the opposite on
      CF. The women with blockaders thread present values of CF significantly lower
      than those who use another antihypertensive medication; happening the inverse
      thing the blockaders alpha. In our consulting room exists a inadequate use of the
      antihypertensive ones. The WCE is significantly mayor when is submitted to
      pharmacological treatment.

PMID- 14635610
TI  - In vitro antigiardial activity of IRE-6A and IRE-7B, two ethyl-phenylcarbamate
      derivatives.
AB  - Resistance is a practical problem associated to the use of benzimidazoles in the
      antigiardial therapy. Since benzimidazole-resistant strains of fungi have shown
      increased sensitivity to phenylcarbamates, in this study we synthesized and in
      vitro tested novel substituted phenylcarbamates against the protozoa Giardia
      intestinalis. IRE-6A and IRE-7B, two 4-R-ethyl-phenylcarbamates demonstrated an
      important antigiardial activity although that was modest when compared to
      albendazole in axenic cultures of Giardia intestinalis. Results of this study
      suggest a potential role of phenylcarbamates as alternative to benzimidazoles in
      the therapy of giardiasis.

PMID- 14635611
TI  - [A new thrombophilia risk factor: the increase of plasma factor VIII].
AB  - Factor VIII (FVIII) is key component of the fluid phase of the blood coagulation
      system. Recent evidence suggests a direct relationship between high plasma levels
      of FVIII and an increased risk for arterial and venous thrombosis. Thus material
      reviews the most important clinical and epidemiological evidence about this
      prothrombotic association. Main function of FVIII is to activate FX functioning
      as a cofactor for activated FIX in the presence of phospholipids and calcium.
      Since its deficiency has been historically associated with a hemorrhagic disease
      (namely hemophilia A), it was never studied its role in thrombosis. In order to
      explain the association FVIII and thrombosis, defects in its synthesis that
      increase its plasma concentration as well as postranslational modifications that
      allow a higher activity, have been proposed. Since 1977 it was suggested that
      increased plasma concentrations of FVIII and thrombosis may be associated.
      Shortly after, several other studies confirmed this association. Indeed, patients
      with stroke of acute myocardial infarction having high plasma levels of FVIII
      have a shorter survival. On the other hand, deep venous thrombosis is more
      frequent in patients with high plasma levels of FVIII. This rise in plasma FVIII
      concentration is also associated with recurrent venous thrombosis. The increment
      of plasma FVIII concentration is not due to an acute phase reaction. Plasma
      concentrations of FVIII above 100-150 IU/dL increase 3-fold the risk of
      thrombosis while concentrations above 150 IU/dL increase the the same risk 6
      fold. While it is established the real importance of FVIII as a cause of
      thrombosis, every patient at risk of thrombosis must have a quantification of
      this factor. Evaluation of plasma FVIII concentration must be performed in
      patients with suspected thrombophilia since there is evidence that shows that
      high plasma FVIII levels is an independent thrombophilic risk factor. There are
      not effective therapeutic interventions able to normalize the high concentrations
      of FVIII. Therefore, appropriate prophylaxis during high thrombosis risk clinical
      episodes is the best alternative for the patient.

PMID- 14635612
TI  - [Cytomegalovirus infections in adults].

PMID- 14635613
TI  - [Alveolar epithelial barrier in patients with acute respiratory distress syndrome
      (ARDS)].
AB  - The clearance of alveolar fluid depends on the anatomic and physiologic integrity
      of alveolar epithelial barrier. The vectorial transport of sodium begins at the
      apical surface in the type II cell through amiloride-sensitive sodium channel.
      Sodium is pumping by Na, K-ATPasa from the basolateral surface of type II cell to
      the interstice. Water passes through specialized channels in the type I cell
      membrane by the osmotic gradient created by sodium. The activity of the sodium
      transporters is regulated actively by genetics and depends on molecular processes
      that involve the hormonal stimulation. The damage to the epithelial membrane
      produces an increased of the permeability of great molecules, which favors
      generation of edema in the alveolar space, delay in the resolution and incapacity
      to regenerate epithelium. More clinic trials are required to demonstrate the
      paper of the transport of chloride and to clarify the true function of the
      specialized water channels in the regulation of the alveolar fluid clearance.

PMID- 14635614
TI  - ACOG committee opinion. Nonobstetric surgery in pregnancy. Number 284, August
      2003.
AB  - Although there are no data to support specific recommendations regarding
      nonobstetric surgery and anesthesia in pregnancy, it is important for
      nonobstetric physicians to obtain obstetric consultation before performing
      nonobstetric surgery. The decision to use fetal monitoring should be
      individualized, and each case warrants a team approach for optimal safety of the
      woman and her baby.

PMID- 14635615
TI  - Oncodiagnosis panel: 2002. Patient's symptoms not related to the lesion seen in
      the MR images.

PMID- 14635616
TI  - Oncodiagnosis panel: 2002. Primary glial neoplasm or less likely an intracranial
      abscess.

PMID- 14635617
TI  - Oncodiagnosis panel: 2002. Optic nerve glioma or optic nerve meningioma.

PMID- 14635618
TI  - Colon and rectal surgery without mechanical bowel preparation: a randomized
      prospective trial.

PMID- 14635619
TI  - Omentoplasty for liver abscess complicating perforative colonic diverticulum.

PMID- 14635620
TI  - Endobronchial findings of fibrosing mediastinitis.
AB  - Fibrosing mediastinitis is underdiagnosed because of the nonspecific character of
      the presenting symptoms. The endobronchial findings obtained via flexible
      bronchoscopy are not defined in the literature. We describe 3 cases of fibrosing
      mediastinitis, most likely caused by histoplasmosis. All 3 patients presented
      with hemoptysis and were found to have tracheobronchial concentric narrowing,
      severe hyperemia, and mucosal edema. The hyperemic blood vessels were treated
      with neodymium yttrium-aluminum-garnet (Nd:YAG) laser and argon plasma
      coagulation. We believe that recognition of specific endobronchial findings aids
      in prompt diagnosis of fibrosing mediastinitis.

PMID- 14635621
TI  - Stewards of public trust: responsible transplantation.

PMID- 14635622
TI  - [The impact of human gene sequence mapping on medical advancement in 21st
      century].

PMID- 14635623
TI  - [Emphasis on etiological diagnosis of chronic cough].

PMID- 14635624
TI  - What's in a beat?

PMID- 14635625
TI  - Inhaled nitric oxide for ARDS: searching for a more focused use.

PMID- 14635626
TI  - Health status after critical illness: beyond descriptive studies.

PMID- 14635627
TI  - The Secundy legacy: a mentor to the bioethics community.

PMID- 14635628
TI  - Can anyone authorize the nontherapeutic permanent alteration of a child's body?

PMID- 14635629
TI  - Testing therapies less effective than the best current standard: ethical beliefs
      in an international sample of researchers.
AB  - To test the range of beliefs regarding the ethics of testing, in resource poor
      settings, new therapies that are less efficacious but more affordable and
      feasible than the best current therapeutic standard.

PMID- 14635630
TI  - How not to argue about circumcision.

PMID- 14635631
TI  - Providing reproductive care to HIV-1 serodiscordant couples: final thoughts.

PMID- 14635632
TI  - About autonomy.

PMID- 14635633
TI  - Justice as equitable power relations: beyond the "standard of care" debate and
      the Declaration of Helsinki.

PMID- 14635634
TI  - Will the "secular priests" of bioethics work among the sinners?
AB  - In this paper I explore briefly the "secular priesthood" metaphor often applied
      to bioethicists. I next ask: if, despite our discomfort with the metaphor, we
      were to embrace the best aspects of the priesthood(s)--which I identify as the
      missionaries' willingness to work among sinners and lepers, at their own peril-
      would we be able to live up to that standard of bravery? I then draw a parallel
      with the fears of contagion currently be voiced (by Carl Elliott and others),
      with regard to bioethicists working in or near coporate settings. I argue that
      such fears may themselves have a number of deleterious effects, and I suggest
      several possible positive steps in response to that fear.

PMID- 14635636
TI  - [The development tendency of modern implantology].

PMID- 14635635
TI  - Assessment of insulin sensitivity and secretion indices from oral glucose
      tolerance testing in subjects with fasting euglycemia but impaired 2-hour plasma
      glucose.

PMID- 14635637
TI  - Arch width.

PMID- 14635638
TI  - Rapid change challenges SNMTS and its members.

PMID- 14635639
TI  - A private focus on patients in Pittsburgh.

PMID- 14635640
TI  - Managing PET in Sacramento.

PMID- 14635641
TI  - Hal Anger: nuclear medicine's quiet genius.

PMID- 14635642
TI  - Meeting the challenges of fusion imaging.

PMID- 14635643
TI  - Honoring Pierre Dejours: his contribution to the study of the role of the
      arterial chemoreceptors in the regulation of breathing in humans.

PMID- 14635644
TI  - 2P domain K+ channels: novel pharmacological targets for volatile general
      anesthetics.

PMID- 14635645
TI  - Ca2+ responses to hypoxia are mediated by IP3-R on Ca2+ store depletion.

PMID- 14635646
TI  - Functional identification of Kvalpha subunits contributing to the O2-sensitive K+
      current in rabbit carotid body chemoreceptor cells.

PMID- 14635647
TI  - Carotid body chemoreceptor activity in mice deficient in selected subunits of
      NADPH oxidase.

PMID- 14635648
TI  - Glucose sensing cells in the carotid body.

PMID- 14635649
TI  - Effect of mitochondrial inhibitors on type I cells.

PMID- 14635650
TI  - Ascorbate in the carotid body.

PMID- 14635651
TI  - Studies on glomus cell sensitivity to hypoxia in carotid body slices.

PMID- 14635652
TI  - An unusual cytochrome a592 with low PO2 affinity correlates with afferent
      discharge in the carotid body.

PMID- 14635653
TI  - A reevaluation of the mechanisms involved in the secretion of catecholamine
      evoked by 2,4-dinitrophenol from chemoreceptor cells of the rabbit carotid body.

PMID- 14635654
TI  - Enhancing effect of vasopressin on the hyperglycemic response to carotid body
      chemoreceptor stimulation. Role of metabolic variables.

PMID- 14635655
TI  - Immunohistochemical study of the carotid body during acute hypoxia.

PMID- 14635656
TI  - Effect of HERG-like potassium channel blocker on the carotid body chemoreception.

PMID- 14635657
TI  - The effect of methanandamide on isolated type I cells.

PMID- 14635658
TI  - Doxapram stimulates carotid body with different mechanisms from hypoxic
      chemotransduction.

PMID- 14635659
TI  - Neuromuscular blocking agents and carotid body oxygen sensing.

PMID- 14635660
TI  - The pulmonary interstitium: an introductory review.

PMID- 14635661
TI  - Regulation of K+ currents by CO in carotid body type I cells and pulmonary artery
      smooth muscle cells.

PMID- 14635662
TI  - Ionotropic receptors in pulmonary neuroepithelial bodies (NEB) and their possible
      role in modulation of hypoxia signalling.

PMID- 14635663
TI  - Mitochondrial complex II is essential for hypoxia-induced ROS generation and
      vasoconstriction in the pulmonary vasculature.
AB  - Hypoxia induces an increase in the ROS generation by cells of small
      intrapulmonary vessels. Based on our results we suppose that this is caused by a
      switch in the catalytic activity of mitochondrial complex II from succinate
      dehydrogenase to fumarate reductase. Functional complex II is also necessary for
      hypoxic pulmonary vasoconstriction.

PMID- 14635664
TI  - Regulation of the hypoxia-inducible transcription factor HIF-1 by reactive oxygen
      species in smooth muscle cells.

PMID- 14635665
TI  - O2-sensing mechanisms in efferent neurons to the rat carotid body.

PMID- 14635666
TI  - Amyloid peptide-mediated hypoxic regulation of Ca2+ channels in PC12 cells.

PMID- 14635667
TI  - Role of ROS and NO in hypoxia-induced increase in tyrosine hydroxylase-messenger
      RNA in PC12 cells.

PMID- 14635668
TI  - Oxygen sensing by human recombinant tandem-P domain potassium channels.

PMID- 14635669
TI  - Oxygen sensing by human recombinant large conductance, calcium-activated
      potassium channels. Regulation by acute hypoxia.

PMID- 14635670
TI  - Potential oxygen sensing pathways in the zebrafish gill.

PMID- 14635671
TI  - Sensory neurons of rat and mice dorsal root ganglia respond to hypoxia with
      increased NO generation.

PMID- 14635672
TI  - Molecular mechanisms of oxygen-induced regulation of Na+/K+ pump.

PMID- 14635673
TI  - The paraganglia of the rat superior laryngeal nerve.

PMID- 14635674
TI  - Dye and electric coupling between carotid nerve terminals and glomus cells.

PMID- 14635675
TI  - Neurotransmitter relationships in the hypoxia-challenged cat carotid body.

PMID- 14635676
TI  - ACh differentially modulates voltage-gated K channels in glomus cells between
      DBA/2J and A/J strains of mice.

PMID- 14635677
TI  - Hypoxic augmentation of neuronal nicotinic acetylcholine receptors and carotid
      body function.

PMID- 14635678
TI  - Cholinergic actions on carotid chemosensory system.

PMID- 14635679
TI  - Nicotinic acetylcholine receptor channels in cat chemoreceptor cells.

PMID- 14635680
TI  - Hypoxia does not uniformly facilitate the release of multiple transmitters from
      the carotid body.

PMID- 14635681
TI  - Expression and function of presynaptic neurotransmitter receptors in the
      chemoafferent pathway of the rat carotid body.

PMID- 14635682
TI  - Adenosine-acetylcholine interactions at the rat carotid body.

PMID- 14635683
TI  - Diverse cholinergic receptors in the cat carotid chemosensory unit.

PMID- 14635684
TI  - Carotid chemosensory neurons in the petrosal ganglia are excited by ACh and ATP.

PMID- 14635685
TI  - The use of NK-1 receptor null mice to assess the significance of substance P in
      the carotid body function.

PMID- 14635686
TI  - Concomitant effect of acetylcholine and dopamine on carotid chemosensory activity
      in catecholamine depleted cats.

PMID- 14635687
TI  - Contribution of neural and endothelial isoforms of the nitric oxide synthase to
      the inhibitory effects of NO on the cat carotid body.

PMID- 14635688
TI  - Nitric oxide and calcium binding protein in hypoxic rat carotid body.

PMID- 14635689
TI  - Carotid body nitric oxide activity in spontaneously diabetic BB rat.

PMID- 14635690
TI  - Contribution of dopamine D2 receptors for the cAMP levels at the carotid body.

PMID- 14635691
TI  - Chemosensitivity of medullary respiratory neurones. A role for ionotropic P2X and
      GABA(A) receptors.

PMID- 14635692
TI  - Effects of controller dynamics on simulations of irregular and periodic
      breathing.

PMID- 14635693
TI  - CO2/H+ signal transduction and central ventilatory control.

PMID- 14635694
TI  - Differential expression of intracellular acidosis in rat brainstem regions in
      response to hypercapnic ventilation.
AB  - We determined the regional intracellular pH (pHi) of rat brainstem in response to
      hypercapnia. Neutral red spectrophotometry was used to characterize changes in
      intracellular pH along the dorsal and ventral aspects of the medulla oblongata.
      Male Wistar rats (250-350 g) were infused with 3 ml of 2% Neutral Red over the
      course of 30 minutes. After 20 minutes of infusion, the rats were ventilated with
      either 7% CO2, 21% O2 in N2 or room air for 15 minutes. Our data indicate that
      hypercapnia induces prominent intracellular acidification in neurons within
      putative chemosensitive regions of the ventral aspect of medulla oblongata. On
      the contrary, minimal or no changes were observed in neurons within the nucleus
      tractus solitarius. These findings suggest that brainstem neurons differentially
      regulate intracellular pH during hypercapnic stress.

PMID- 14635695
TI  - Tentative role of the Na+/H+ exchanger type 3 in central chemosensitivity of
      respiration.

PMID- 14635696
TI  - Effect of losartan microinjections into the NTS on the cardiovascular components
      of chemically evoked reflexes in a rabbit model of acute heart ischemia.
AB  - In the acute phase of myocardial infarction (MI) there are modifications of the
      autonomic outflow with an increase in the sympathetic tone and changes in
      cardiovascular reflexes. Activation of angiotensin AT1 receptors in the nucleus
      tractus solitarii (NTS) inhibits the baroreceptor and enhances the carotid
      chemoreflex. In this study, we investigated the role of NTS-AT1 receptors on the
      cardiovascular reflex responses evoked on stimulation of carotid chemoreflex and
      cardiac chemosensitive fibres in the acute phase of MI. We also test the
      hypothesis that changes in cardiovascular responses to activation of carotid
      chemo and cardiac chemosensitive reflexes are secondary to changes in
      haemodynamic conditions due to infarction or to the activation of nociceptors of
      the heart. Rabbits were anaesthetised, paralysed and artificially ventilated.
      Carotid chemoreceptors and cardiac chemosensitive fibres were stimulated with
      lobeline and ATP, respectively. Arterial blood pressure, electrocardiogram and
      heart rate were monitored. A craniotomy was made to expose the caudal portions of
      the medulla and a multibarreled glass microelectrode was inserted in order to
      allow the identification of NTS and the microinjection of losartan (an
      angiotensin AT1 receptor antagonist). The heart was exposed by a midline
      thoracotomy and cardiac ischemia was produced by ligating the left descending
      coronary artery. The carotid chemoreflex and cardiac chemosensitive reflexes were
      evoked before and following the coronary ligation. The effect of losartan
      injection into the NTS on these reflexes was also assessed. In control
      experiments reflexes were assessed before and after the administration of
      capsaicin and procainamide. Results show that the activation of carotid
      chemoreflex elicited a greater increase of blood pressure and bradycardia after
      MI and that this was partially reversed by losartan microinjection after MI. Also
      the stimulation of cardiac chemosensitive fibres evoked a larger decrease on
      blood pressure and heart rate after MI and these were also partially reversed by
      losartan. The same enhancement of cardiovascular carotid chemo and cardiac
      chemosensitive receptors was observed after administration of capsaicin on the
      ventricular surface but not after procainamide. In conclusion, this study
      strongly suggests that, at NTS level, angiotensin AT1 receptors are involved in
      the modifications of autonomic outflow observed in the acute phase of MI.

PMID- 14635697
TI  - Effects of acute hypoxic conditions on extracellular excitatory amino acids and
      dopamine in the striatum of freely-moving rats.

PMID- 14635698
TI  - Activity of dorsal medullary respiratory neurons in awake rats.

PMID- 14635699
TI  - Cardiovascular and respiratory responses to heme oxygenase inhibition in
      conscious rats.

PMID- 14635700
TI  - Peripheral chemoreceptor input to cardiac vagal preganglionic neurones in the
      anaesthetised rat.

PMID- 14635701
TI  - Hypoxic remodelling of Ca2+ homeostasis in rat type I cortical astrocytes.

PMID- 14635702
TI  - Effect of CO2 on cardiovascular regulation in conscious rats.

PMID- 14635703
TI  - A6 noradrenergic cell group modulates the hypoxic ventilatory response.

PMID- 14635704
TI  - Ventilatory chemosensory drive in cats, rats and guinea-pigs.

PMID- 14635705
TI  - Deletion of tachykinin NK1 receptor gene in mice does not alter respiratory
      network maturation but alters respiratory responses to hypoxia.

PMID- 14635706
TI  - Autonomic ganglion cells: likely source of acetylcholine in the rat carotid body.

PMID- 14635707
TI  - Effects of perinatal hyperoxia on carotid body chemoreceptor activity in vitro.

PMID- 14635708
TI  - Prenatal hypoxia and early postnatal maturation of the chemoafferent pathway.

PMID- 14635709
TI  - pH sensitivity of spinal cord rhythm in fetal mice in vitro.

PMID- 14635710
TI  - Time dependent regulation of dopamine D1- and D2-receptor gene expression in the
      carotid body of developing rabbits by hypoxia.

PMID- 14635711
TI  - Ventilatory response to CO2 in new born mouse.

PMID- 14635712
TI  - Long-term effects of neonatal cryoanesthesia on hypoxic ventilatory response in
      weanling rats depend on neonatal testosterone.

PMID- 14635713
TI  - Systemic and cellular responses to intermittent hypoxia: evidence for oxidative
      stress and mitochondrial dysfunction.

PMID- 14635714
TI  - Effects of hypobaric hypoxia on the intercellular coupling of glomus cells.

PMID- 14635715
TI  - Oxygen sensing by human recombinant large conductance, calcium-activated
      potassium channels. Regulation by chronic hypoxia.

PMID- 14635716
TI  - Altered expression of vascular endothelial growth factor and FLK-1 receptor in
      chronically hypoxic rat carotid body.

PMID- 14635717
TI  - Role of HIF-1 in physiological adaptation of the carotid body during chronic
      hypoxia.

PMID- 14635719
TI  - Rat carotid bodies in systemic hypoxia. Involvement of arterial CO2 tension in
      morphological changes.

PMID- 14635718
TI  - Carotid body HIF-1alpha, VEGF and NOS expression during aging and hypoxia.

PMID- 14635720
TI  - Immunohistochemical study of the carotid body just after arousal from
      hibernation.

PMID- 14635721
TI  - 3D QSAR studies on binding affinities of coumarin natural products for glycosomal
      GAPDH of Trypanosoma cruzi.
AB  - Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have
      been used to predict the activity of new compounds. The major advantage of this
      approach is that it permits the analysis of a large number of quantitative
      descriptors and uses chemometric methods such as partial least squares (PLS) to
      correlate changes in bioactivity with changes in chemical structure. Because it
      is often difficult to rationalize all variables affecting the binding affinity of
      compounds using CoMFA solely, the program GRID was used to describe ligands in
      terms of their molecular interaction fields, MIFs. The program VolSurf that is
      able to compress the relevant information present in 3D maps into a few
      descriptors can treat these GRID fields. The binding affinities of a new set of
      compounds consisting of 13 coumarins, for one of which the three-dimensional
      ligand-enzyme bound structure is known, were studied. A final model based on the
      mentioned programs was independently validated by synthesizing and testing new
      coumarin derivatives. By relying on our knowledge of the real physical data
      (i.e., combining crystallographic and binding affinity results), it is also shown
      that ligand-based design agrees with structure-based design. The compound with
      the highest binding affinity was the coumarin chalepin, isolated from Rutaceae
      species, with an IC50 value of 55.5 microM towards the enzyme glyceraldehyde-3
      phosphate dehydrogenase (gGAPDH) from glycosomes of the parasite Trypanosoma
      cruzi, the causative agent of Chagas' disease. The proposed models from GRID MIFs
      have revealed the importance of lipophilic interactions in modulating the
      inhibition, but without excluding the dependence on stereo-electronic properties
      as found from CoMFA fields.

PMID- 14635722
TI  - MCASE study of the multidrug resistance reversal activity of propafenone analogs.
AB  - A database containing 130 propafenone type chemicals which have been tested for
      their multidrug resistance (MDR) reversal activity was compiled. Using the
      Multiple Computer-Automated Structure Evaluation (MCASE) program to analyze this
      database, an underlying relationship between MDR reversal activity and
      octanol/water partition coefficient was found. An MDR reversal model was created
      based on this database by the baseline activity identification algorithm (BAIA)
      of the MCASE program. The main phamacophores relevant to MDR reversal activity
      were identified.

PMID- 14635723
TI  - Comparative binding energy analysis of haloalkane dehalogenase substrates:
      modelling of enzyme-substrate complexes by molecular docking and quantum
      mechanical calculations.
AB  - We evaluate the applicability of automated molecular docking techniques and
      quantum mechanical calculations to the construction of a set of structures of
      enzyme-substrate complexes for use in Comparative binding energy (COMBINE)
      analysis to obtain 3D structure-activity relationships. The data set studied
      consists of the complexes of eighteen substrates docked within the active site of
      haloalkane dehalogenase (DhlA) from Xanthobacter autotrophicus GJ10. The results
      of the COMBINE analysis are compared with previously reported data obtained for
      the same dataset from modelled complexes that were based on an experimentally
      determined structure of the DhlA-dichloroethane complex. The quality of fit and
      the internal predictive power of the two COMBINE models are comparable, but
      better external predictions are obtained with the new approach. Both models show
      a similar composition of the principal components. Small differences in the
      relative contributions that are assigned to important residues for explaining
      binding affinity differences can be directly linked to structural differences in
      the modelled enzyme-substrate complexes: (i) rotation of all substrates in the
      active site about their longitudinal axis, (ii) repositioning of the ring of
      epihalohydrines and the halogen substituents of 1,2-dihalopropanes, and (iii)
      altered conformation of the long-chain molecules (halobutanes and halohexanes).
      For external validation, both a novel substrate not included in the training
      series and two different mutant proteins were used. The results obtained can be
      useful in the future to guide the rational engineering of substrate specificity
      in DhlA and other related enzymes.

PMID- 14635724
TI  - CoMFA and docking study of novel estrogen receptor subtype selective ligands.
AB  - We present the results from a Comparative Molecular Field Analysis (CoMFA) and
      docking study of a diverse set of 36 estrogen receptor ligands whose relative
      binding affinities (RBA) with respect to 17beta-Estradiol were available in both
      isoforms of the nuclear estrogen receptors (ER alpha, ER beta). Initial CoMFA
      models exhibited a correlation between the experimental relative binding
      affinities and the molecular steric and electrostatic fields; ER alpha: r2 =
      0.79, q2 = 0.44 ER beta: r2 = 0.93, q2 = 0.63. Addition of the solvation energy
      of the isolated ligand improved the predictive nature of the ER beta model
      initially; r2 = 0.96, q2 = 0.70 but upon rescrambling of the data-set and
      reselecting the training set at random, inclusion of the ligand solvation energy
      was found to have little effect on the predictive nature of the CoMFA models. The
      ligands were then docked inside the ligand binding domain (LBD) of both ER alpha
      and ER beta utilizing the docking program Gold, after-which the program CScore
      was used to rank the resulting poses. Inclusion of both the Gold and CScore
      scoring parameters failed to improve the predictive ability of the original CoMFA
      models. The subtype selectivity expressed as RBA(ER alpha/ER beta) of the test
      sets was predicted using the most predictive CoMFA models, as illustrated by the
      cross-validated r2. In each case the most selective ligands were ranked correctly
      illustrating the utility of this method as a prescreening tool in the development
      of novel estrogen receptor subtype selective ligands.

PMID- 14635725
TI  - 2-Pyridone and 3-oxo-1,2,6-thiadiazine-1,1-dioxide derivatives: a new class of
      hydrogen bond equivalents of uracil.
AB  - Hydrogen bond complex stability between adenine (A) and hydrogen bond equivalents
      of uracil: 2-pyridone derivatives (U(X2O)X) and 3-oxo-1,2,6-thiadiazine-1,1
      dioxide derivatives (U(SO2)X) was studied, and as the result, the hydrogen bond
      energy of U(X2O)X-A and a complex of UX(SO2)X-A, was about 1.5 kcal/mol more
      stable than that of the corresponding adenine-uracil derivatives complex,
      respectively. The energy difference between the imide tautomer and enol tautomer
      was smaller than those of uracil derivatives. U(SO2)F can form a stable complex
      with A, and its imide tautomer is stable.

PMID- 14635726
TI  - ANVAS: artificial neural variables adaptation system for descriptor selection.
AB  - A new algorithm model-oriented for variable selection is presented in this study.
      It is based on the combination of genetic algorithms (GA) for hyperspace
      exploration, and counterpropagation artificial neural network (CP ANN) for
      deriving the fitness score. The proposed method performed very well on both well
      defined synthetic data sets and real academic data sets.

PMID- 14635727
TI  - Evaluation of extended parameter sets for the 3D-QSAR technique MaP: implications
      for interpretability and model quality exemplified by antimalarially active
      naphthylisoquinoline alkaloids.
AB  - The 3D-QSAR technique MaP (Mapping Property distributions of molecular surfaces)
      characterises biologically active compounds in terms of the distribution of their
      surface properties (H-bond donor, H-bond acceptor, hydrophilic, weakly
      hydrophobic, strongly hydrophobic). The MaP descriptor is alignment-independent
      and yields chemically intuitive models. In this study, the impact of different
      operational parameters on the interpretability and model quality was
      investigated. Based on a set of antimalarially active naphthylisoquinoline
      alkaloids the effect of hydrophobicity assignment as well as the differentiation
      of H-bond propensity was evaluated according to a full factorial design. It turns
      out, that including different categories for H-bond donor strength significantly
      improved interpretability, reduced model complexity, and made possible the
      derivation of a novel pharmacophore hypothesis for this dataset. Further analysis
      of the factorial design reveals, that MaP models are robust to parameter changes
      and generate consistent models for different parameter settings.

PMID- 14635729
TI  - Binding of alpha-hydroxy-beta-amino acid inhibitors to methionine aminopeptidase.
      The performance of two types of scoring functions.
AB  - The binding mode of a recently described set of alpha-hydroxy-beta-amino acid
      inhibitors of methionine aminopeptidase type 2 is suggested in the present work.
      The binding mode is supported by analysis of published structures of transition
      state analogues co-crystallised with E. coli methionine aminopeptidase and by a
      comparison of molecular interaction fields calculated using GRID for E. coli and
      human methionine aminopeptidase. Based on the suggested binding mode two types of
      scoring functions have been evaluated and compared. These are the commercially
      available consensus score, CScore, and scoring of the ligands employing energies
      calculated using the Merck Molecular Force Field (MMFF). Enriched subsets of
      ligands were obtained when using CScore, but these scores could not be used to
      assess the relative affinities of individual compounds. Although still not
      sufficiently accurate for reliable predictive purposes, an improved correlation
      was obtained between structure and affinity using a combined force field energy
      including contributions from solvation and conformational energy penalty for
      binding.

PMID- 14635728
TI  - Molecular model of the neural dopamine transporter.
AB  - The dopamine transporter (DAT) regulates the action of dopamine by reuptake of
      the neurotransmitter into presynaptic neurons, and is the main molecular target
      of amphetamines and cocaine. DAT and the Na+/H+ antiporter (NhaA) are secondary
      transporter proteins that carry small molecules across a cell membrane against a
      concentration gradient, using ion gradients as energy source. A 3-dimensional
      projection map of the E. coli NhaA has confirmed a topology of 12 membrane
      spanning domains, and was previously used to construct a 3-dimensional NhaA model
      with 12 trans-membrane alpha-helices (TMHs). The NhaA model, and site directed
      mutagenesis data on DAT, were used to construct a detailed 3-dimensional DAT
      model using interactive molecular graphics and empiric force field calculations.
      The model proposes a dopamine transport mechanism involving TMHs 1, 3, 4, 5, 7
      and 11. Asp79, Tyr252 and Tyr274 were the primary cocaine binding residues.
      Binding of cocaine or its analogue, (-)-2beta-carbomethoxy-3beta-(4
      fluorophenyl)tropane (CFT), seemed to lock the transporter in an inactive state,
      and thus inhibit dopamine transport. The present model may be used to design
      further experimental studies of the molecular structure and mechanisms of DAT and
      other secondary transporter proteins.

PMID- 14635730
TI  - Intima-media thickness of the carotid arteries in subjects with hyperinsulinaemia
      (insulin resistance).
AB  - The metabolic syndrome is characterised by hyperinsulinaemia (insulin resistance)
      leading to an increased risk of atherosclerotic cardiovascular diseases. Carotid
      intima-media thickness (IMT) can be easily measured to detect early
      atherosclerosis. In order to evaluate the clinical characteristics of the
      metabolic syndrome a screening procedure was performed and carotid IMT was
      determined by high-resolution B-mode ultrasonography in a cohort of middle-aged
      (40-60 years) subjects who proved to be hyperinsulinaemic [fasting plasma insulin
      >15 microU/ml and/or post-prandial (120 min) insulin > 45 microU/ml; n = 91;
      men/women: 35/56; homeostasis model assessment (HOMA)-index: 6.42 +/- 3.65; x +/-
      SD]. Subjects known to have diabetes were not involved. Subjects were divided
      into subgroups according to the stages of glucose intolerance (normal glucose
      tolerance, n = 46; impaired glucose tolerance, n = 26; diabetes mellitus, n =
      19). As controls, age- and sex-matched non-diabetic and non-hyperinsulinaemic
      subjects (n = 20; HOMA-index: 2.09 +/- 0.85) were investigated. The values of IMT
      of the internal carotid arteries were higher in hyperinsulinaemic subjects than
      in controls (0.93 +/- 0.39 mm vs 0.57 +/- 0.13 mm,p < 0.001), whereas the lumen
      diameter proved to be smaller than in control subjects (5.04 +/- 0.75 mm vs 5.45
      +/- 0.71 mm; p < 0.05). In hyperinsulinaemic subjects only a trend of increasing
      IMT values and that of decreasing lumen diameter of the internal carotid arteries
      were observed when subgroups classified according to the stages of glucose
      intolerance were compared. No significant changes in IMT or lumen diameter of the
      common carotid arteries were observed. Early and asymptomatic signs of
      atherosclerosis could be detected in middle-aged subjects who proved to be
      hyperinsulinaemic in a screening procedure. The prevention of clinically manifest
      cardiovascular diseases in these subjects could be of great importance.

PMID- 14635731
TI  - Psychiatric distress and health-related quality of life in obesity.
AB  - Health-related quality of life (HRQL) is poor in obese patients and not
      necessarily related to the severity of disease. In a large proportion of patients
      psychopathological distress is also present and its role on poor HRQL has never
      been quantified. METHODS: In 207 patients entering a University-based weight
      reducing programme (38 males, 169 females), a package of self-administered
      questionnaires was submitted to measure HRQL (Short-Form 36) and
      psychopathological distress [general: Symptom Check-List 90 (SCL-90); depression:
      Beck Depression Inventory (BDI); binge eating: Binge Eating Scale (BES)]. Several
      clinical and anthropometric data were also recorded. RESULTS: HRQL, both in its
      physical and mental component, was significantly reduced in obesity when related
      to Italian population norms. SCL-90 identified psychopathological distress in 53
      patients (26%), the BDI was indicative of depression in 89 cases (43%), whereas
      high scores of the BES were measured in 88 cases. Logistic regression analysis
      identified psichopathological distress as the major factor associated with poor
      HRQL. CONCLUSIONS: Psychiatric disturbances significantly contribute to poorly
      perceived health status. Only a comprehensive treatment including a specific
      approach to psychiatric symptoms may be effective in improving the perceived
      health status of obese patients seeking treatment.

PMID- 14635732
TI  - Diabetes and non-traumatic lower extremity amputation in a region of central
      Italy.
AB  - As stated in the St. Vincent Declaration, the reduction of the number of lower
      extremity amputations (LEA) is one of the major targets in diabetes care. Little
      information on the prevalence of this complication is available in Italy at
      present. The aim of this study was to evaluate the impact of diabetes on LEA in a
      region of central Italy. The regional database of hospital discharge records was
      used to identify all the cases of non-traumatic LEA (Nt-LEA) that had occurred in
      1997 and 1998. Diagnosis of diabetes and the type of surgical intervention were
      defined on the basis of the medical records. Amputations were categorised as
      minor or major according to the level of the surgical procedure. The duration of
      hospitalisation was used to analyse the impact of diabetes on the health care
      system. Prevalence of diabetes in people who underwent Nt-LEA was 55.9% and it
      was similar in patients who underwent minor or major amputation (58.7 and 55.0%,
      respectively). No difference between diabetic and non-diabetic patients was
      observed as regards sex, level of amputation and duration of hospitalisation. Age
      was the only predictor of diabetes in amputees. The lack of specific protocols
      for diabetes foot care or a non-homogeneous application of these protocols in the
      health care service could account for a similar prevalence of diabetes among
      patients who underwent minor or major amputation.

PMID- 14635733
TI  - Autoantibodies against glutamic acid decarboxylase and 21-hydroxylase in
      Brazilian patients with type 1 diabetes or autoimmune thyroid diseases.
AB  - Autoimmune thyroid diseases (ATD) are often associated with Type 1 diabetes
      mellitus (T1DM) and Addison's disease (AD), characterizing the autoimmune
      polyendocrine syndrome. We evaluated the frequency of autoantibodies against
      glutamic acid decarboxylase isoform 65 (GAD65Ab) and 21-hydroxylase (21OHAb) in
      the sera of 65 [58 females (F)/7 males (M), 17-70 yr] patients with Graves'
      disease (GD) and 47 (45 F/2 M, 12-77 yr) with Hashimoto's thyroiditis (HT), none
      of whom had either diabetes or AD. The sera of 30 recently diagnosed T1DM
      patients (16 M/14 F, 1-39 yr) and of 97 (54 F/43 M, 7-69 yr) healthy controls
      were also examined. GAD65Ab were detected in the sera of 18 (60%) T1DM, 8 (12%)
      GD and in none of the HT patients or the controls (p = 0.03 for GD vs HT, p =
      0.002 for GD vs controls, and p < 0.001 for GD vs T1DM). 21OHAb were detected in
      the sera of 2 (3%) GD, 1 (2%) HT and in none of the T1DM patients or the
      controls. GAD65Ab levels were significantly lower in GD than in T1DM patients
      (median: -0.06 vs 0.28, p < 0.001). Six of the 8 GD GAD65Ab-positive patients
      submitted to an intravenous glucose tolerance test showed no diminished first
      phase insulin secretion. All 21OHAb positive patients had normal basal cortisol
      and adrenocorticotropin (ACTH), normal cortisol response after ACTH stimulation,
      but high plasma renin activity. In conclusion, despite the genetic diversity of
      the Brazilian population, the frequency of GAD65Ab and 21OHAb in our patients is
      similar to that observed in other countries. GAD65Ab were more prevalent in GD
      than in HT patients, suggesting a difference in the immune response between these
      disorders. Long-term follow-up is necessary to determine the clinical relevance
      of these autoantibodies in the Brazilian population.

PMID- 14635734
TI  - Association between the metabolic syndrome and newly diagnosed coronary artery
      disease.
AB  - This case-control study was designed to outline age- and gender-related
      differences of metabolic risk factors in a group of patients with coronary artery
      disease (CAD). Accordingly, a total of 366 consecutive patients with a recent
      diagnosis of CAD (139 women, 41-79 yr; 227 men, 39-78 yr) were screened between
      October 1999 and April 2001 at Baskent University Adana Medical Center, and 366
      age- and gender-matched individuals were selected as a control group. We compared
      demographics, blood pressure, body mass index, waist circumference, lipid
      profile, fasting and post-prandial glucose-insulin levels between CAD patients
      and the control group. Prevalence of metabolic syndrome was 72.6% in females, and
      39.0% in males with CAD. Hypertension, obesity and diabetes were more common in
      female patients; 64.5% of female patients had premature CAD and 83.5% of those
      had metabolic syndrome. In logistic (OR: 3.57 for women and OR: 1.59 for men)
      regression analysis, metabolic syndrome was independently associated with CAD in
      both genders. As a conclusion, prevalence of metabolic syndrome was significantly
      higher in patients with CAD than the control group, especially in female
      patients. The metabolic syndrome was independently associated with CAD in both
      genders.

PMID- 14635735
TI  - Determination of endothelial function and early atherosclerotic changes in
      healthy obese women.
AB  - The aim of this study was to determine the associations between vascular
      endothelial function, intima-media thickness (IMT) of the common carotid artery
      and anthropometric/metabolic parameters in healthy obese women without obesity
      related metabolic complications and age-matched healthy lean controls. Twenty
      four obese [body mass index (BMI) > 30 kg/m2; age 31.4 +/- 7.4 yr] and 14 lean
      (BMI < 24 kg/m2; age 30.5 +/- 7.2 yr) women were studied. All of the subjects had
      normolipemia. Insulin resistance was calculated according to the homeostasis
      model assessment (HOMA) formula. Endothelial function was measured by flow
      mediated dilation (FMD) of the brachial artery. IMT of the common carotid artery
      was calculated from high-resolution ultrasound imaging of the two common carotid
      arteries. Obese and lean women were matched with respect to age, smoking status,
      blood pressure, glucose, insulin concentrations and HOMA. IMT of common carotid
      artery was significantly higher (0.56 +/- 0.09 vs 0.45 +/- 0.06 mm, p < 0.001)
      and FMD (percentage of change from baseline) was significantly lower (13.3 +/-
      6.5% vs 25.2 +/- 13.9%,p < 0.001) in the obese subjects. Lipid profile, blood
      pressure, indirect measurement of insulin resistance, leptin concentrations and
      anthropometric parameters did not predict the FMD or IMT in the obese and lean
      groups. It is concluded that even in healthy obese women with a normal metabolic
      profile, deterioration in endothelial function and early atherosclerotic changes
      are evident compared with healthy lean counterparts. Some undetermined factors in
      our study other than obesity-related well-known risk factors could be responsible
      for this observation.

PMID- 14635736
TI  - Liver glycogenosis as early manifestation in type 1 diabetes mellitus.
AB  - Clinical symptoms and biochemical findings related to liver dysfunction are not
      generally reported among the presentation features of Type 1 diabetes mellitus
      (T1DM) in infancy and childhood. To our knowledge this is the first paper
      reporting two children with a clinical and biochemical picture of hepatic
      glycogenosis at the presentation of T1DM. In both cases at beginning of insulin
      therapy liver function and dimensions were absolutely normal, even though
      glycometabolic status had been severely altered for many days at T1DM onset. Both
      hepatomegaly and aminotransferase abnormalities were first found only some days
      after the institution of treatment with supraphysiological insulin doses. In both
      patients the improvement of glycometabolic control under insulin therapy was
      followed within some weeks by a complete physical and biochemical recovery, as
      typically reported in hepatic glycogenosis. These case reports demonstrate that
      hepatic glycogenosis can occur at any stage of T1DM and may even be one of its
      earliest manifestations, together with those classically reported at the onset of
      T1DM. Since long-standing hyperglycaemia and overinsulinisation are metabolic pre
      requisites for hepatic glycogen storage, liver glycogenosis should be expected to
      be not uncommon during the first phases of T1DM, especially in the cases who are
      initially treated with supraphysiological insulin doses.

PMID- 14635737
TI  - Epidemiology and health care planning on diabetes.

PMID- 14635738
TI  - Data sources and validity of epidemiological studies on diabetes.

PMID- 14635739
TI  - The role of general practitioners in epidemiological research.

PMID- 14635740
TI  - Lower extremity amputations in diabetic patients: comparison of regional
      experiences within Italy.

PMID- 14635741
TI  - A feasibility study in Reggio Emilia, Italy.

PMID- 14635742
TI  - Statistical methods for surveillance of diabetes events.

PMID- 14635743
TI  - Questions in health care planning and answers from epidemiology.

PMID- 14635744
TI  - RIDI: the registry of type 1 diabetes in Italy.

PMID- 14635745
TI  - Immune suppression and isolated severe head injury: a significant clinical
      problem.
AB  - In the developed world, trauma is the principal cause of death under the age of
      40 and is the third largest overall killer. In the UK, approximately 25,000
      people die each year as a result of major injury, 25% as a result of head
      injuries alone. Despite improved diagnosis and management, infection remains the
      commonest complication in those patients surviving the initial injury. Some 5%
      are reported to die as a result of septic complications. Prolonged periods of
      intensive care and respiratory support predispose to infective respiratory
      complications. These patients in the absence of significant systemic injury and,
      as a result of severe head injury, are unable to mount an effective immune
      response. This literature review examines the changes that have been reported to
      occur in the immune system following isolated severe head injury and explores the
      relationship these changes may have to the increased development of infective
      complications.

PMID- 14635746
TI  - Clinical experience with porous tantalum cervical interbody implants in a
      prospective randomized controlled trial.
AB  - A prospective randomized study was undertaken to evaluate the radiological
      appearance and clinical effectiveness of two porous tantalum (Hedrocel) implants
      in achieving a stable cervical interbody fusion. A prerandomization protocol was
      used to allocate patients to the three arms of the study: a ring implant
      containing autologous cancellous bone graft, a solid block implant or autologous
      tricortical iliac crest bone graft. Patients were followed for 2 years with plain
      radiological studies, SF-36, and Neck Disability Index questionnaires and
      neurological assessment. Early in the study the postoperative radiographs of four
      patients receiving Hedrocel implants showed inferior end-plate lucency raising
      concerns about delayed or non-fusion. Recruitment to the study was halted by the
      investigators to allow longer-term follow-up of the implanted patients when only
      24 patients had been recruited to the study. Although fusion was subsequently
      noted in all patients at 12 months there was no further enrolment to the study.
      At 2 years the radiological and clinical outcomes of the three groups appeared
      comparable, but the study numbers were too small for any statistical analysis.
      This study highlights the difficulties that can arise when clinical caution takes
      precedence over objective measures of clinical progress during a study. In the
      absence of an independent safety monitoring committee, the investigators were
      under an ethical obligation to suspend recruitment to this study, until it was
      clear that the radiological features were not associated with poor clinical
      outcomes. The use of safety monitoring committees and the clarification of
      stopping criteria in relation to outcome measures should be considered in open
      randomized trials of spinal surgical techniques and implants.

PMID- 14635747
TI  - Clinical databases and data protection: are they compatible?
AB  - In the current climate of clinical governance and audit, and in the setting of an
      active academic unit, an effective clinical database is an invaluable tool. In
      this article, we will present our neurovascular database, discuss the issues
      related to setting up the ideal clinical database, discuss the problems related
      to accurate data input and review the legal requirements of data protection. The
      success of a clinical database is reflected by the completeness of the data, the
      accessibility of the information and how useful it has proven to be. After 4
      years of experimentation we currently use a database designed on Microsoft
      Access. The form is a single page. Junior medical staff input the information as
      medical staff have been found to be the most reliable personnel for data input in
      terms of accuracy. However, time is generally in short supply amongst this group.
      For our purposes, the ideal database is one that is simple, that can be used to
      flag up cases, rather than provide all of the information and ensures a complete
      dataset. The arrival of the UK 1998 Data Protection Act has put many clinical
      databases and registries in jeopardy, and introduced further bureaucracy to
      research. We discuss the Act and its interpretation by the General Medical
      Council, Medical Research Council, British Medical Association, Department of
      Health and our own trust with respect to databases and research.

PMID- 14635748
TI  - The role of parenteral nutrition as a supplement to enteral nutrition in patients
      with severe brain injury.
AB  - Enteral nutrition (EN) is the preferred and safe route of feeding in surgical
      patients incapable of self-nutrition. We describe three patients with severe
      brain insult and recurrent sepsis, who despite the early introduction of EN,
      remained hypoalbuminaemic, hypoproteinaemic and developed peripheral oedema. This
      state persisted, despite increasing the caloric and protein intake via the
      enteral route. However, after a short course of supplemental parenteral nutrition
      (PN), albumin and total protein levels improved, with resolution of peripheral
      oedema. We hypothesize that, in certain critically ill neurosurgical patients on
      EN, gastrointestinal malabsorption may underlie a persistently low serum albumin,
      total protein and peripheral oedema. A short course of supplemental PN may help
      to reverse this and a normal regimen of EN can then be continued.

PMID- 14635749
TI  - Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing
      transsphenoidal pituitary surgery: a prospective randomized controlled study.
AB  - We report the results of a prospective randomized controlled trial, which looked
      at the incidence of postoperative diabetes insipidus (DI) following the use of
      three different hydrocortisone protocols, and the results of a study, on the
      incidence of DI and cortisol response in patients not given hydrocortisone. In
      study 1, 114 patients with pituitary macroadenoma were randomized into three
      groups: conventional dose (inj. hydrocortisone 100 mg IV 6-hourly for 3 days);
      intermediate dose (inj. hydrocortisone 100 mg IV 6-hourly on day 1, 100 mg IV 8
      hourly on day 2, and 100 mg IV 12-hourly on day 3); low dose protocol (inj.
      hydrocortisone 25 mg IV 6-hourly on day 1, 25 mg IV 8-hourly on day 2 and 25 mg
      IV 12-hourly on day 3). Radical excision was achieved in 92 patients. The
      incidence of DI with the conventional dose was 52%, intermediate dose, 36% and
      low dose, 24% (p = 0.025). Study 2 included 16 consecutive patients with Hardy's
      grade A & B pituitary adenoma. These patients were randomized to receive (Group
      I) or not receive (Group II) hydrocortisone. Patients in Group II demonstrated
      normal cortisol response intraoperatively and no patient developed features of
      hypocortisolism; the incidence of DI in this group was 14%. The low dose
      hydrocortisone protocol reduced the incidence of DI by 46% when compared with the
      conventional dose hydrocortisone protocol. In patients with grade A and B tumour
      with normal preoperative cortisol levels, the use of perioperative hydrocortisone
      can be avoided.

PMID- 14635750
TI  - Stereotactic MR imaging for planning neural transplantation: a reliable technique
      at 3 Tesla?
AB  - The purpose of this study was to assess the accuracy of high field (3 Tesla) MR
      in target localization for stem cell transplantation. Three patients with
      Huntington's disease were imaged with a stereotactic frame in place for both MRI
      and CT. Quality assurance procedures and manual shimming were performed before
      each MRI study to minimize image distortion. The images were fused using multi
      modality rigid body image registration software. Image fusion demonstrated the MR
      images to be in agreement with CT to within 1.5 mm, as assessed by measuring the
      coordinates of markers on the frame and on the shape and size of the lateral
      ventricles. Target coordinates for transplantation were selected from the MR
      images. Postoperative imaging confirmed accurate graft placement.

PMID- 14635751
TI  - Surgical treatment of intracranial hypertension in encephalic cryptococcosis.
AB  - The incidence of cryptococcosis has risen sharply together with the growing
      number of patients with Acquired Immunodeficiency Syndrome (AIDS). Cryptococcal
      meningitis is nowadays the most common intracranial non-viral infection in such
      cases. One of its most serious complications is intracranial hypertension (ICH),
      a situation that can lead either to early death, or disabling sequelae. The
      authors analyse a series of 10 cases of encephalic cryptococcosis with ICH, and
      describe the clinical course, diagnosis, medical and surgical treatment, and
      evolution. The physiopathology of ICH in these patients is discussed, proposing
      placement of a ventriculo-peritoneal shunt as the primary and emergency
      treatment, even when ventricular enlargement might be absent. Although the
      present series is certainly small, from the preceding discussion and according to
      an extensive bibliographical review, our conclusion is that patients with
      encephalic cryptococcosis and uncontrollable ICH should receive surgical
      treatment, consisting of an emergency diversion of the CSF, because serial lumbar
      punctures are not enough to improve the clinical course, that if left to its
      natural evolution would lead to a fatal outcome in a short time. In spite of the
      fact that CSF shunts were carried out on immunocompromised patients, no
      superinfections occurred.

PMID- 14635752
TI  - Spontaneous intracranial hypotension causing confusion and coma: a headache for
      the neurologist and the neurosurgeon.
AB  - Spontaneous intracranial hypotension presenting with confusion and coma has
      rarely been reported. A case is presented and the clinical features of
      spontaneous intracranial hypotension are discussed.

PMID- 14635753
TI  - Metastatic adenocarcinoma masquerading as a solitary nerve sheath tumour.
AB  - We present a case of a solitary metastasis of an adenocarcinoma to a dorsal root
      ganglion (DRG) following a disease free interval of 12 years after resection of a
      Duke's C carcinoma. The presentation of this unusually placed metastasis was
      associated with a 3-year complex pain syndrome and radiological appearances
      consistent with benign disease. The case highlights the importance of not
      dismissing unusual lesions as innocent in the presence of a history of malignant
      disease.

PMID- 14635754
TI  - Haemangioblastoma: a rare cause of a cerebellar mass in the elderly.
AB  - In the elderly, cerebellar lesions are commonly metastatic tumours with poor
      prognosis. We describe two octogenarians who presented with obstructive
      hydrocephalus, secondary to posterior fossa tumours that, on computed tomography,
      were thought to be cerebellar metastases. Both lesions were excised and the
      histology proved them to be cerebellar haemangioblastomas, primary benign tumours
      of the posterior fossa, which are rare in the elderly.

PMID- 14635755
TI  - Spontaneous intracranial migration of the shunt chamber.

PMID- 14635756
TI  - Diffuse idiopathic skeletal hyperostosis resulting in dysphagia and aspiration
      pneumonia.

PMID- 14635757
TI  - A benign pilomatrixoma mimicking a skull vault tumour in a 9-month-old girl.

PMID- 14635758
TI  - Development of posterior circulation aneurysm in association with bilateral
      internal carotid artery occlusion.

PMID- 14635759
TI  - Peripheral T-cell lymphoma presenting as a solitary vermian mass.

PMID- 14635761
TI  - Topology: a novel method to describe branching patterns in Peronospora viciae
      colonies.
AB  - Topology provides a novel means to describe branching patterns and has not been
      applied to fungal colonies previously. For any branched structure, various
      topologies are possible, and these lie between two extremes, a herringbone
      pattern (main axis with primary laterals) and a dichotomous pattern (highly
      branched system). We applied topological methods to colonies of Peronospora
      viciae 48 h after inoculation of Pisum sativum leaves. The methods are based on
      two simulations, one developed for channel networks such as found in river
      systems and another for biological systems. Although not a true herringbone form,
      the Peronospora viciae colonies have a strong herringbone element within their
      growth pattern. All 25 colonies analysed fell into the random distribution
      according to the confidence limits calculated from simulations for biological
      systems. These confidence limits, however, represent the percentile distribution
      of all simulated networks, and only those structures with a perfect herringbone
      or dichotomous topology fall outside the range. The tendency of P. viciae
      colonies towards herringbone growth is reflected by the topological indices for
      altitude and external pathlength (a(obs)/E(a) and pe(obs)/E(pe), where a =
      altitude, pe = external pathlength, obs = observed for the P. viciae colonies and
      E = expected values for random growth), and the slope of the regression analysis
      for a(obs) and pe(obs). We consider this trend as significant because it was
      consistent for all but one of the colonies, and implies that growth can be
      envisaged as an intermediate between random and herringbone topology. It is
      proposed that initial herringbone growth may reflect a strategy that is aimed at
      overcoming host resistance, achieving rapid colonisation of infected tissue and
      maximising the potential for nutrient acquisition. This topology would also
      increase the likelihood of finding a compatible mating type for reproduction
      between heterothallic isolates.

PMID- 14635762
TI  - Phylogenetic relationships of Peronospora and related genera based on nuclear
      ribosomal ITS sequences.
AB  - In order to investigate phylogenetic relationships of selected members of
      Peronosporaceae to the genera Pythium, Halophkytophthora, Phytophthora, and
      Peronophythora, Bayesian analysis of partial sequences of the ITS1-5.8S-ITS2
      region was performed. In addition, sequences of the complete ITS1-5.8S-ITS2
      region were analysed for 101 collections belonging to the genera Peronospora,
      Hyaloperonospora, Perofascia, Pseudoperonospora, Phytophthora and Peronophythora,
      using Bayesian inference of phylogeny and maximum parsimony. The results confirm
      a close relationship of these genera. The strongly supported Peronosporaceae
      clade is located within the paraphyletic genus Phytophthora (including
      Peronophythora). Monophyly of the genera Pseudoperonospora and Hyaloperonospora
      are strongly supported, but monophyly of Peronospora s. str. can neither be
      confirmed nor rejected. Within Peronospora s. str., basic relationships often
      remain unclear; however, some groups form highly supported monophyletic clades.
      Peronospora species parasitising the same host families or orders are only partly
      resolved as monophyletic, indicating frequent host-jumping also between distantly
      related host families. All species inhabiting flowers of different host families
      form a strongly supported monophyletic group.

PMID- 14635763
TI  - Morphological and molecular phylogenetic studies in South American Cortinarius
      species.
AB  - Thirty South American species of Cortinarius belonging to the subgenera
      Telamonia, Dermocybe, Myxacium, Phlegmacium, and Cystogenes were studied using an
      integrated approach that included morphological, anatomical, and ultrastructural
      data, and also molecular phylogenetic analysis of nuclear rDNA sequences. The
      micromorphology of the basidiomes was studied by light microscopy, and the
      principal structures were illustrated by line drawings. Basidiospore
      ornamentation was studied by scanning electron microscopy (SEM). Nuclear internal
      transcribed spacers (ITS, including the 5.8S gene) and the rDNA coding for the
      D1/D2 domains of the large ribosomal subunit (LSU) were sequenced and analysed
      using a Bayesian Markov chain Monte Carlo method to estimate phylogenetic
      relationships between the studied Cortinarius species. Morphology and anatomy of
      the pileus surface and basidiome pigmentation appeared to be the most useful
      characters to delimit some natural groups, whereas microcharacters related to the
      structure of pileus context, hymenophoral and stipe trama were of little
      taxonomic value. Basidiospore morphology and cheilocystidia seem to be
      taxonomically relevant at the species level. The following five infrageneric
      groups were supported by the morphological, chemical and molecular data: (1)
      Telamonia characterized by wide hyaline hyphae of the veil and by small
      basidiomes; (2) Dermocybe spp. with an epicutis as the most external layer of the
      pileus, and skyrin and hypericin pigments; (3) Dermocybe spp. with a thin viscid
      layer on the pileus, and endocrocin and dermolutein pigments; (4) Phlegmacium
      spp. characterized by a long and radicating stipe; and (5) Phlegmacium spp. that
      overlap in some macrocharacters with Telamonia species. Our analyses suggest that
      classification concepts based mainly on macromorphological characters are likely
      to lead to artificial grouping, whereas certain microscopical and chemical
      characters seem to be useful in constructing a more natural classification system
      for Cortinarius.

PMID- 14635764
TI  - Distribution of Amanita spp. genotypes under eastern Australian sclerophyll
      vegetation.
AB  - Basidiomes of Amanita alboverrucosa, A. ochrophylla, and A. pyramidifera were
      collected from native mixed sclerophyll forest sites and of A. conicoverrucosa
      and A. punctata from planted stands of Eucalyptus maculata in New South Wales,
      Australia. DNA was extracted from stipe tissue and subjected to inter-simple
      sequence repeat (ISSR) PCR analysis conducted using the primers (GTG)5 and
      (GACA)4 in order to determine genotype distribution at each site. Two to nine
      genotypes of one of the species were identified at each field site. Genotypes of
      A. ochrophylla, A. conicoverrucosa and A. punctata were spread over areas of ca
      10-60 m diam, suggesting vegetative spread via large below-ground mycelial
      genets. In contrast, genotypes of A. alboverrucosa were more spatially
      restricted, suggesting recent establishment via basidiospores and more limited
      below-ground vegetative spread. Two groups of A. pyramidifera basidiomes that
      were separated by ca 600 m were found to be of the same genotype. While this
      might reflect long distance spread of below-ground mycelium in this taxon, the
      proximity of the basidiomes to a roadway makes movement of vegetative basidiome
      tissue via vehicular activity and subsequent establishment equally plausible.

PMID- 14635765
TI  - Analysis of nrDNA sequences and microsatellite allele frequencies reveals a
      cryptic chanterelle species Cantharellus cascadensis sp. nov. from the American
      Pacific Northwest.
AB  - In the Pacific Northwest, yellow chanterelles have long been referred to as
      Cantharellus cibarius, synonymous with the European yellow chanterelle. Broad
      scale genetic surveys of North American chanterelles with C. cibarius-like
      morphology have demonstrated that the nrDNA internal transcribed spacer exhibits
      length variability, suggesting that this common morphology masks a species
      complex. Recently researchers have used morphological and genetic data to
      identify the yellow chanterelle most frequently harvested from American Pacific
      Northwest forests as C. formosus, a species once thought to be rare in the
      region. We present three genetic data sets and one morphological data set that
      characterize a previously undescribed, species of yellow chanterelle from the
      central Cascade Mountains of Oregon. Phylogenetic analyses of the nrDNA large
      subunit and ITS regions show that C. cascadensis sp. nov., along with two other
      yellow chanterelle taxa (C. cibarius var. roseocanus and European C. cibarius),
      are more closely related to white chanterelles (C. subalbidus) than they are to
      C. formosus. Data from five microsatellite loci provide evidence that C.
      formosus, C. subalbidus, and C. cascadensis sp. nov. do not interbreed when they
      co-occur spatially and temporally in Douglas fir-western hemlock forests. This
      demonstrates that these three sympatric chanterelles are biological species with
      boundaries congruent with those delineated by nrDNA phylogenetic clades.
      Morphological data indicate that the colour of the pileus and shape of the stipe
      can be used to separate fresh collections of the two yellow species now known to
      co-occur in Douglas fir-western hemlock forests in Oregon.

PMID- 14635766
TI  - Characterization of field-isolates and derived DMI-resistant strains of
      Cercospora beticola.
AB  - Cercospora beticola strains with laboratory induced resistance to tetraconazole
      were compared with their parental WT sensitive strains to evaluate the effects of
      resistance on fitness and assess whether any change in the sterol biosynthetic
      pathway was associated to the reduced fungicide sensitivity. In vitro growth rate
      on agar media and pathogenicity were found to be negatively affected by
      resistance. The main functional sterols in C. beticola WT strains under
      investigation were ergosterol, brassicasterol and ergosta-7,22-dienol. Resistant
      strains showed the same qualitative sterol composition, ruling it out as, per se,
      a cause for resistance. On the basis of the sterols detected both in sensitive
      and resistant strains, a possible biosynthetic pathway to the three functional
      sterols is proposed. Tetraconazole treatment caused, in all sensitive strains,
      the immediate accumulation of 14alpha-methylated sterols, which, for inhibitor
      concentrations up to EC50 values, were, in order of abundance, 14alpha
      methylergosta-8,24(28)-dien-3beta,6alpha-diol, eburicol and obtusifoliol. However
      the data do not support a critical role of the 14-methyl-3,6-diol derivative in
      the growth arrest of C. beticola. As main difference between sensitive and
      resistant strains, the formers were found to accumulate higher amounts of 14alpha
      methylated sterols. Although the data do not allow to establish a specific
      mechanism for resistance, some molecular mechanisms such as target site
      alterations and sterol biosynthetic pathway can be ruled out as a possible cause
      for reduced sensitivity.

PMID- 14635767
TI  - Nuclear large subunit rDNA group I intron distribution in a population of
      Beauveria bassiana strains: phylogenetic implications.
AB  - Four group I introns, designated Bb1, Bb2, Bb3 and Bb4, were identified in the
      entomopathogenic hyphomycete Beauveria bassiana. Sequence analyses of these
      introns verified that they were invariably inserted at specific target sequences
      after conserved positions Ec2563, Ec2449, Ec2066 and Ec1921 of the large nuclear
      subunit (LSU) rDNA 3'-end. Secondary structure modelling confirmed that Bb1 and
      Bb3 belonged to subgroup IE while Bb2 and Bb4 belonged to subgroup IC1. Intron
      presence, distribution and size-variation were studied in a population of 125 B.
      bassiana strains using site-specific primers. Nucleotide sequences and secondary
      structures were compared and showed considerable variations usually at P1, P6 and
      P9 helices, but concomitantly, high homology between members of the same site
      specific group. Intron distribution studies revealed that few (7.2%) strains were
      intron-less, most contained one (28%), two (48%) or three (16%) introns, while
      only one strain contained all four introns. Bb4-like introns (Ec1921) were the
      most abundant (86.4%), whereas the other three introns were evenly represented
      (ca 30%) in the B. bassiana population. Analysis of intron genotype distribution
      indicated a tenuous dependence upon geographic origin or insect host species.
      Phylogenetic analysis of all B. bassiana LSU introns and their close relatives
      from other entomopathogenic fungi showed a strong correlation between specific
      insertion sites and intron subgroups, fully supported by corresponding clades,
      suggesting common ancestry of the site specific LSU introns.

PMID- 14635768
TI  - Novel illudins from Coprinopsis episcopalis (syn. Coprinus episcopalis), and the
      distribution of illudin-like compounds among filamentous fungi.
AB  - The illudins are a family of fungal sesquiterpenes that have been studied as anti
      tumor agents, and they also have antibacterial activity. Over a four-year period,
      25 304 fungal isolates (approximately 97% ascomycetes and 3% basidiomycetes),
      were screened for antibacterial activity against methicillin-resistant
      Staphylococcus aureus. Illudin-like compounds with antibacterial and cytotoxic
      activity against tumor cell lines were observed in 10 basidiomycete strains. The
      isolates were recovered from different types of substrata using indirect methods
      and only formed sterile mycelia in pure culture. The isolates were genetically
      related but not identical, based on PCR-based fingerprinting techniques. DNA
      sequencing of the ITS1-5.8 S-ITS2 region of the strains revealed that nine had
      identical sequences, indicating that they were conspecific. The sequence of the
      remaining isolate was 96.34% similar, suggesting that it was a closely related
      species. The D1-D2 region of the 25 S rRNA gene of the two strain types was also
      sequenced. Both sequences were 99.39% similar, and Coprinopsis gonophylla (syn.
      Coprinus gonophyllus) was the closest match for both. Strains were grown in pure
      culture on a rice-based medium that allowed the development of basidiomata from
      one culture of the main strain type, which was identified as C. episcopalis, a
      close relative of C. gonophyllus. Both species (or strain types) produced
      different types of illudin-like compounds. Three novel illudins (I, I2 and J2)
      were found to be produced by the cultures identified as C. episcopalis, while
      only illudinic acid was produced by the other Coprinopsis sp. The taxonomical
      relationships of the Coprinops is species identified in this study with other
      illudin producers previously reported in the literature are discussed.

PMID- 14635769
TI  - Development of in situ and ex situ seed baiting techniques to detect mycorrhizal
      fungi from terrestrial orchid habitats.
AB  - An innovative ex situ fungal baiting method using soil collected from field sites
      which allows the simultaneous detection of mycorrhizal fungi for multiple
      terrestrial orchids is presented. This method demonstrated that coarse organic
      matter (> 2 mm) in the litter and topsoil was the most important reservoir of
      inoculum of these fungi. A new in situ seed baiting method using multi-chambered
      packets to simultaneously assess germination for different orchid species within
      soil is also introduced. These in situ and ex situ methods are compared using
      seed of orchids in the genera Monadenia, Microtis, Caladenia, Pterostylis and
      Diuris, using urban Banksia woodland sites with high or low weed cover. Both
      these seed baiting methods detected compatible fungi for these orchids, but
      common orchids germinated more frequently than those which were uncommon at the
      field sites. Germination rates were not significantly affected by weed cover even
      though adult orchids were rare in areas with high weed cover. The two new seed
      baiting methods vary in efficiency and applicability depending on the situation
      where they are used. However, the ex situ method allowed the time-course of
      germination to be observed, resulting in the production of more protocorms and
      facilitation of the isolation of mycorrhizal fungi. These techniques provide
      valuable new tools for detection of compatible mycorrhizal fungi to assist orchid
      research and conservation.

PMID- 14635770
TI  - Local variations in microfungal populations on Pinus sylvestris needles.
AB  - We studied the fungal colonization of Pinus sylvestris needles in two
      neighbouring sites, comparing stands of isolated and grouped trees. We observed
      large variations among the proportions of needles bearing fruit bodies of
      Cyclaneusma minus, Lophodermium pinastri, Verticicladium trifidum and black lines
      characteristic of L. pinastri colonization. Variations between sites and within
      trees were greater than that between stands or between trees. The frequency of L.
      pinastri colonization was negatively correlated with C. minus fruit body
      frequency, while the frequency of V. trifidum conidiophores was positively
      correlated with L. pinastri colonization frequency without fruiting, and
      negatively correlated with C. minus apothecia frequency. Although L. pinastri
      black lines and C. minus apothecia were nearly randomly associated on individual
      needles in each sample, the two fungi occupied different segments when they
      occupied the same needle. These patterns at needle and sample scales do not
      explain the negative correlation between the frequencies of these two species
      observed at larger scales. In each sample, frequency of V. trifidum conidiophores
      was highest on needles colonized by L. pinastri without fruiting. On individual
      needles, V. trifidum conidiophores developed on segments colonized by L. pinastri
      without fruiting, but not on segments bearing fruit bodies of L. pinastri or C.
      minus. These patterns at needle and sample scales were consistent with the
      correlations between frequencies observed at larger scales. These results were
      compared to variations observed with stand age and climate in others studies. The
      observed variations might result from both microclimate variations and fungal
      interactions.

PMID- 14635771
TI  - Ophiostoma kryptum sp. nov. from Larix decidua and Picea abies in Europe, similar
      to O. minus.
AB  - An unknown species of Ophiostoma was isolated from European larch (Larix decidua)
      infested by Tetropium gabrieli (Coleoptera: Cerambycidae) and Norway spruce
      (Picea abies) infested by Tetropium sp. in Austria. The fungus is similar to O.
      minus, but distinguished from it by the ecology, colony morphologies on OA and
      MEA, and phylogenetic analysis of aligned DNA sequences of the ITS region of the
      rDNA operon and the partial beta-tubulin gene. It is described here as O. kryptum
      sp. nov. The new species readily produces perithecia with short necks and
      reniform ascospores, and has Hyalorhinocladiella and Leptographium-like
      anamorphs. Circumstantial evidence suggests that Tetropium spp. act as vectors of
      O. kryptum. O. minus and O. kryptum represent additional examples of
      morphologically similar, yet genetically and ecologically distinct species in the
      genus Ophiostoma. The new combination, O. crenulatum comb. nov. (syn.
      CeratocYstiopsis crenulata), is also made.

PMID- 14635772
TI  - Albatrellus citrinus sp. nov., connected to Picea abies on lime rich soils.
AB  - Field observations indicated that a morphotype of Albatrellus subrubescens seemed
      connected to Picea abies and lime rich soils, while the original morphotype
      seemed connected with Pinus sylvestris and indifferent to lime. We conducted a
      molecular study (ITS sequencing of 22 Albatrellus specimens) to test the
      hypothesis that we in fact had discovered a new species. Our results confirmed
      the hypothesis, i.e. the Picea taxon (604 bp ITS) had little intraspecific
      variation in spite of 1600 km distance between samples, but compared with the
      Pinus taxon (598 bp ITS) the sequence difference was constantly 5.6% regardless
      of close distance (75 km). We describe the new species A. citrinus, which apart
      from ecology and ITS sequence, is different from A. subrubescens by a distinct
      yellowing with age, lack of dark spots of the cap, a mild taste and somewhat
      narrower spores. A. citrinus seems to be more related to A. ovinus than to A.
      subrubescens, and A. syringae may not even be a true Albatrellus.

PMID- 14635773
TI  - Introduction: A close look at the vacuolar ATPase.
AB  - The vacuolar ATPases (V-type ATPases) are a family of ATP-dependent ion pumps and
      found in two principal locations, in endomembranes and in plasma membranes. This
      family of ATPases is responsible for acidification of intracellulare compartments
      and, in certain cases, ion transport across the plasma membrane of eucaryotic
      cells. V-ATPases are composed of two distinct domains: a catalytic V1 sector, in
      which ATP hydrolysis takes place, and the membrane-embedded sector, V0, which
      functions in ion conduction. In the past decade impressive progress has been made
      in elucidating the properties structure, function and moleculare biology. These
      knowledge sheds light also on the evolution of V-ATPases and their related
      families of A-(A1A0-ATPase) and F-type (F1F0-ATPases) ATPases.

PMID- 14635774
TI  - A journey from mammals to yeast with vacuolar H+-ATPase (V-ATPase).
AB  - The vacuolar H+-ATPase (V-ATPase) is one of the most fundamental enzymes in
      nature. It functions in almost every eukaryotic cell and energizes a wide variety
      of organelles and membranes. V-ATPase has a structure and mechanism of action
      similar to F-ATPase and several of their subunits probably evolved from common
      ancestors. In eukaryotic cells, F-ATPase is confined to the semiautonomous
      organelles, chloroplasts and mitochondria, which contain their own genes that
      encode some of the F-ATPase subunits. In contrast to F-ATPases, whose primary
      function in eukaryotic cells is to form ATP at the expense of the protonmotive
      force (pmf), V-ATPases function exclusively as ATP-dependent proton pumps. The
      pmf generated by V-ATPases in organelles and membranes of eukaryotic cells is
      utilized as a driving force for numerous secondary transport processes. It was
      the survival of the yeast mutant without the active enzyme and yeast genetics
      that allowed the identification of genuine subunits of the V-ATPase. It also
      revealed special properties of individual subunits, factors that are involved in
      the enzyme's biogenesis and assembly, as well as the involvement of V-ATPase in
      the secretory pathway, endocytosis, and respiration. It may be the insect V
      ATPase that unconventionally resides in the plasma membrane of their midgut, that
      will give the first structure resolution of this complex.

PMID- 14635775
TI  - Subunit structure, function, and arrangement in the yeast and coated vesicle V
      ATPases.
AB  - The vacuolar (H+)-ATPases (or V-ATPases) are ATP-dependent proton pumps that
      function both to acidify intracellular compartments and to transport protons
      across the plasma membrane. Acidification of intracellular compartments is
      important for such processes as receptor-mediated endocytosis, intracellular
      trafficking, protein processing, and coupled transport. Plasma membrane V-ATPases
      function in renal acidification, bone resorption, pH homeostasis, and, possibly,
      tumor metastasis. This review will focus on work from our laboratories on the V
      ATPases from mammalian clathrin-coated vesicles and from yeast. The V-ATPases are
      composed of two domains. The peripheral V1 domain has a molecular mass of 640 kDa
      and is composed of eight different subunits (subunits A-H) of molecular mass 70
      13 kDa. The integral V0 domain, which has a molecular mass of 260 kDa, is
      composed of five different subunits (subunits a, d, c, c', and c'') of molecular
      mass 100-17 kDa. The V1 domain is responsible for ATP hydrolysis whereas the V0
      domain is responsible for proton transport. Using a variety of techniques,
      including cysteine-mediated crosslinking and electron microscopy, we have defined
      both the overall shape of the V-ATPase and the V0 domain as well as the location
      of various subunits within the complex. We have employed site-directed and random
      mutagenesis to identify subunits and residues involved in nucleotide binding and
      hydrolysis, proton translocation, and the coupling of these two processes. We
      have also investigated the mechanism of regulation of the V-ATPase by reversible
      dissociation and the role of different subunits in this process.

PMID- 14635776
TI  - Structure and assembly of the yeast V-ATPase.
AB  - The yeast V-ATPase belongs to a family of V-type ATPases present in all
      eucaryotic organisms. In Saccharomyces cerevisiae the V-ATPase is localized to
      the membrane of the vacuole as well as the Golgi complex and endosomes. The V
      ATPase brings about the acidification of these organelles by the transport of
      protons coupled to the hydrolysis of ATP. In yeast, the V-ATPase is composed of
      13 subunits consisting of a catalytic V1 domain of peripherally associated
      proteins and a proton-translocating V0 domain of integral membrane proteins. The
      regulatory subunit, Vma13p, was the first V-ATPase subunit to have its crystal
      structure determined. In addition to proteins forming the functional V-ATPase
      complex, three ER-localized proteins facilitate the assembly of the V0 subunits
      following their translation and insertion into the membrane of the ER. Homologues
      of the Vma21p assembly factor have been identified in many higher eukaryotes
      supporting a ubiquitous assembly pathway for this important enzyme complex.

PMID- 14635777
TI  - Assembly and regulation of the yeast vacuolar H+-ATPase.
AB  - The yeast vacuolar proton-translocating ATPase (V-ATPase) is an excellent model
      for V-ATPases in all eukaryotic cells. Activity of the yeast V-ATPase is
      reversibly down-regulated by disassembly of the peripheral (V1) sector, which
      contains the ATP-binding sites, from the membrane (V0) sector, which contains the
      proton pore. A similar regulatory mechanism has been found in Manduca sexta and
      is believed to operate in other eukaryotes. We are interested in the mechanism of
      reversible disassembly and its implications for V-ATPase structure. In this
      review, we focus on (1) characterization of the yeast V-ATPase stalk subunits,
      which form the interface between V1 and V0, (2) potential mechanisms of silencing
      ATP hydrolytic activity in disassembled V1 sectors, and (3) the structure and
      function of RAVE, a recently discovered complex that regulates V-ATPase assembly.

PMID- 14635778
TI  - Subunit composition, structure, and distribution of bacterial V-type ATPases.
AB  - The overall structure of V-ATPase complexes resembles that of F-type ATPases, but
      the stalk region is different and more complex. Database searches followed by
      sequence analysis of the five water-soluble stalk region subunits C-G revealed
      that (i) to date V-ATPases are found in 16 bacterial species, (ii) bacterial V
      ATPases are closer to archaeal A-ATPases than to eukaryotic V-ATPases, and (iii)
      different groups of bacterial V-ATPases exist. Inconsistencies in the
      nomenclature of types and subunits are addressed. Attempts to assign subunit
      positions in V-ATPases based on biochemical experiments, chemical cross-linking,
      and electron microscopy are discussed. A structural model for prokaryotic and
      eukaryotic V-ATPases is proposed. The prokaryotic V-ATPase is considered to have
      a central stalk between headpiece and membrane flanked by two peripheral stalks.
      The eukaryotic V-ATPases have one additional peripheral stalk.

PMID- 14635779
TI  - Structure and function of the vacuolar H+-ATPase: moving from low-resolution
      models to high-resolution structures.
AB  - In the absence of a high-resolution structure for the vacuolar H+-ATPase, a
      number of approaches can yield valuable information about structure/function
      relationships in the enzyme. Electron microscopy can provide not only a
      representation of the overall architecture of the complex, but also a low
      resolution map onto which structures solved for individually expressed subunits
      can be fitted. Here we review the possibilities for electron microscopy of the
      Saccharomyces V-ATPase and examine the suitability of V-ATPase subunits for
      expression in high yield prokaryotic systems, a key step towards high-resolution
      structural studies. We also review the role of experimentally-derived structural
      models in understanding structure/function relationships in the V-ATPase, with
      particular reference to the complex of proton-translocating 16 kDa proteolipids
      in the membrane domain of the V-ATPase. This model in turn makes testable
      predictions about the sites of binding of bafilomycins and the functional
      interactions between the proteolipid and the single-copy membrane subunit Vph1p,
      with implications for the constitution of the proton translocation pathway.

PMID- 14635780
TI  - Vacuolar H+ pumping ATPases in luminal acidic organelles and extracellular
      compartments: common rotational mechanism and diverse physiological roles.
AB  - Cytoplasmic organelles with an acidic luminal pH include vacuoles, coated
      vesicles, lysosomes, the Golgi apparatus, and synaptic vesicles. Acidic
      compartments are also known outside specialized cells such as osteoclasts. The
      unique acidic pH is formed by V-ATPase (Vacuolar type ATPase), other ion
      transporters, and the buffering action of proteins inside the organelles. V
      ATPase hydrolyzes ATP and transports protons inside an organelle or extracellular
      compartment. We have summarized recent progress on mouse V-ATPases and their
      varying localizations together with their mechanism emphasizing similarities with
      F-type ATPases.

PMID- 14635781
TI  - The insect plasma membrane H+ V-ATPase: intra-, inter-, and supramolecular
      aspects.
AB  - The plasma membrane H+ V-ATPase from the midgut of larval Manduca sexta, commonly
      called the tobacco hornworm, is the sole energizer of epithelial ion transport in
      this tissue, being responsible for the alkalinization of the gut lumen up to a pH
      of more than 11 and for any active ion movement across the epithelium. This
      minireview deals with those topics of our recent research on this enzyme that may
      contribute novel aspects to the biochemistry and physiology of V-ATPases. Our
      research approaches include intramolecular aspects such as subunit topology and
      the inhibition by macrolide antibiotics, intermolecular aspects such as the
      hormonal regulation of V-ATPase biosynthesis and the interaction of the V-ATPase
      with the actin cytoskeleton, and supramolecular aspects such as the interactions
      of V-ATPase, K+/H+ antiporter, and ion channels, which all function as an
      ensemble in the transepithelial movement of potassium ions.

PMID- 14635782
TI  - Vacuolar proton pumps in malaria parasite cells.
AB  - The malaria parasite is a unicellular protozoan parasite of the genus Plasmodium
      that causes one of the most serious infectious diseases for human beings. Like
      other protozoa, the malaria parasite possesses acidic organelles, which may play
      an essential role(s) in energy acquisition, resistance to antimalarial agents,
      and vesicular trafficking. Recent evidence has indicated that two types of
      vacuolar proton pumps, vacuolar H+-ATPase and vacuolar H+-pyrophosphatase, are
      responsible for their acidification. In this mini-review, we discuss the recent
      progress on vacuolar proton pumps in the malaria parasite.

PMID- 14635783
TI  - New insight into the structure and regulation of the plant vacuolar H+-ATPase.
AB  - Plant cells are characterized by a highly active secretory system that includes
      the large central vacuole found in most differentiated tissues. The plant
      vacuolar H+-ATPase plays an essential role in maintaining the ionic and metabolic
      gradients across endomembranes, in activating transport processes and vesicle
      dynamics, and, hence, is indispensable for plant growth, development, and
      adaptation to changing environmental conditions. The review summarizes recent
      advances in elucidating the structure, subunit composition, localization, and
      regulation of plant V-ATPase. Emerging knowledge on subunit isogenes from
      Arabidopsis and rice genomic sequences as well as from Mesembryanthemum
      illustrates another level of complexity, the regulation of isogene expression and
      function of subunit isoforms. To this end, the review attempts to define
      directions of future research on plant V-ATPase.

PMID- 14635784
TI  - L-Selectin ligands in lymphoid tissues and models of inflammation.
AB  - Both lymphocyte recirculation through the lymphoid tissues and leukocyte
      recruitment to sites of inflammation are essential components of immune
      surveillance, and are necessary for sustained protection against pathogens. This
      process is mediated by the leukocyte-endothelial adhesion cascade of which the
      interaction of leukocyte L-Selectin with its endothelial ligand initiates the
      first critical tethering and rolling step. As well as discussing the constitutive
      L-Selectin ligands in lymphoid tissues, this review examines the literature
      regarding their induction in inflammation, and draws attention to recent findings
      regarding soluble L-Selectin ligands that suggest an emerging multifunctional
      role in leukocyte recirculation and inflammation.

PMID- 14635785
TI  - Inflammation-mediated retinal edema in the rabbit is inhibited by topical
      nepafenac.
AB  - The purpose of this study was to evaluate the ability of the nonsteroidal anti
      inflammatory drug nepafenac to prevent development of mitogen-induced pan-retinal
      edema following topical ocular application in the rabbit. Anesthetized Dutch
      Belted rabbits were injected intravitreally (30 microg/20 microL) with the
      mitogen concanavalin A to induce posterior segment inflammation and thickening
      (edema) of the retina. The Heidelberg Retina Tomograph was used to generate edema
      maps using custom software. Blood-retinal barrier breakdown was assessed by
      determining the protein concentration in vitreous humor, whereas analysis of PGE2
      in vitreous humor was performed by radioimmunoassay. Inhibition of concanavalin A
      induced retinal edema was assessed 72 h after initiation of topical treatment
      with nepafenac (0.1-1.0%, w/v), dexamethasone (0.1%), VOLTAREN (0.1%), or ACULAR
      (0.5%). Concanavalin A elicited marked increases in vitreal protein and PGE2
      synthesis at 72 h postinjection. Retinal thickness was also increased by 32%,
      concomitant with the inflammatory response. Topical application of 0.5% nepafenac
      produced 65% reduction in retinal edema which was correlated with 62% inhibition
      of blood-retinal barrier breakdown. In a subsequent study, 0.5% nepafenac
      significantly inhibited (46%) blood-retinal barrier breakdown concomitant with
      near total suppression of PGE2 synthesis (96%). Neither Voltaren nor Acular
      inhibited accumulation of these markers of inflammation in the vitreous when
      tested in parallel. This study demonstrates that nepafenac exhibits superior
      pharmacodynamic properties in the posterior segment following topical ocular
      dosing, suggesting a unique therapeutic potential for a variety of conditions
      associated with retinal edema.

PMID- 14635786
TI  - Thermal hyperalgesia and light touch allodynia after intradermal Mycobacterium
      butyricum administration in rat.
AB  - We examined the time course (7 weeks) of thermal hyperalgesia and light touch
      allodynia in rats after intradermal administration of Mycobacterium butyricum.
      Nociceptive thresholds to heat and light touch were assessed. Paw edema and
      temperature, motor function, body weight, and propioception were also tested.
      Some rats developed arthritis (named AA rats) but others did not (named non-AA
      rats). Both groups were compared with healthy animals. Persistent hyperalgesia
      was found in both groups; in AA rats it appeared before clinical evidence of
      arthritis. Transient allodynia ocurred only after edema development and fell when
      edema decreased. Motor function was impaired only in AA rats. The results of this
      study demonstrate that hyperalgesia, but not allodynia, appeared after
      Mycobacterium butyricum in both groups, suggesting that changes in sensitivity
      were not merely the result of local hypersensitivity of the inflamed tissue, but
      may also be due to alterations in nociception in the central nervous system.

PMID- 14635787
TI  - Constitutively increased neutrophil surface expression of beta2-integrin in
      Yemenite Jews.
AB  - The aim of this study was to analyze surface expression of neutrophil adhesion
      molecules in Yemenite Jews as compared to other ethnic populations in Israel. The
      constitutive neutrophil expression of CD11b and L-selectin (LS), as well as their
      expression in response to an in vitro chemoattractant and growth factor
      stimulation were studied by flow cytometry. Mean surface expression of CD11b
      molecule was statistically significantly increased among the Yemenite Jews tested
      compared to the non-Yemenite Jews (327.1 +/- 129.2 vs. 237.0 +/- 133.1; p =
      0.002), with no significant correlation to their absolute neutrophil count. LS
      expression was similar in the two study groups. In vitro analysis of CD11b and LS
      expression induced by chemoattractant and G-CSF showed no difference between
      neutrophils of Yemenite versus non-Yemenite Jews. The study results suggest that
      in Yemenite Jews, circulating neutrophils display significantly increased
      expression of beta2-integrin molecules on their surface compared to non-Yemenite
      Jews.

PMID- 14635788
TI  - Bradykinin stimulates MMP-2 production in guinea pig tracheal smooth muscle
      cells.
AB  - The implication of bradykinin (BK) receptors in the release of the matrix
      metalloproteinase-2 (MMP-2; gelatinase A) was studied in guinea pig tracheal
      smooth muscle cells (GP-TSMC). Bradykinin (10(-8)-10(-4) M) induced a time- and
      concentration-dependent upregulation of MMP-2 production from cultured GP-TSMC.
      Pretreatment of the GP-TSMC with the bradykinin B2 receptor (BKB2-R) antagonist
      Hpp-HOE-140 (Hpp-D-Arg0-Hyp3-Thi5-D-Tic7-Oic8-BK; 10(-8)-10(-4) M) significantly
      inhibited the BK-stimulated upregulation of MMP-2 in GP-TSMC in a concentration
      related manner. Conversely, GP-TSMC pretreated with the selective bradykinin B1
      receptor (BKB1-R) antagonist R-954 (Ac-Om[Oic2, alpha-MePhe5, D-betaNal7,
      Ile8]desArg9BK; 10(-8)-10(-4) M) did not show any change in the response to BK.
      Moreover, the selective BKB2-R agonist Lys0BK (kallidin; 10(-8)-10(-4) M)
      stimulated whereas the selective BKB1-R agonist desArg9BK (DBK; 10(-8)-10(-4) M)
      had no effect on MMP-2 release from GP-TSMC. Further, the nonselective
      cyclooxygenase (COX) enzyme inhibitor indomethacin (IND; 10(-5) M), the
      glucocorticosteroid dexamethasone (DEX; 1 ng/mL) and the protein synthesis
      inhibitors, cycloheximide (CHX; 10(-6) M) and actinomycin D (ACT-D; 10(-8) M)
      also inhibited BK-induced MMP-2 release from GP-TSMC. These results provide the
      first evidence for the involvement of BK in the release of MMP-2 from airway
      smooth muscle cells through activation of the BKB2-R. Such response is mostly
      mediated by the induction of COX and the subsequent production of endogenous
      prostaglandins (PGs). It could therefore be suggested that MMP-2 might play a
      role in the process of airway remodeling.

PMID- 14635789
TI  - Histamine dihydrochloride protects against early alcohol-induced liver injury in
      a rat model.
AB  - Inflammation of the liver may be caused by a variety of factors that include
      infectious agents and toxins. Reactive oxygen species (ROS) generated by the
      NADPH oxidase in Kupffer cells and infiltrating leukocytes play an important role
      in the pathogenesis of early alcohol-induced hepatitis. Histamine dihydrochloride
      (histamine) suppresses the generation of ROS through the histamine type-2
      receptor (H2 receptor). Histamine was studied as a potential protective treatment
      against early alcohol-induced liver injury in an experimental hepatitis model.
      Female Wistar rats were given ethanol (5 g/kg) intragastrically by gavage once
      daily for 4 weeks, while a control group not receiving ethanol was fed an
      isocaloric high-fat diet. Animals receiving ethanol had elevated serum levels of
      alanine and aspartate transaminase (ALT/AST) and developed steatosis,
      inflammation, and necrosis of the liver. Histamine treatment (0.5 or 5.0 mg/kg,
      twice daily) protected against this liver injury as evident by normal serum
      transaminase levels and significantly reduced liver pathology scores. Ranitidine
      (10 mg/kg), an H2 receptor antagonist, blocked the protective effect of
      histamine, indicating that the histamine effect is predominantly mediated through
      the H2 receptor. In conclusion, these results suggest that histamine protects
      against early alcohol-induced liver injury in rats.

PMID- 14635790
TI  - Transcription factors.

PMID- 14635791
TI  - Beta-catenin and Tcfs in mammary development and cancer.
AB  - Beta-catenin regulates cell-cell adhesion and transduces signals from many
      pathways to regulate the transcriptional activities of Tcf/Lef DNA binding
      factors. Gene ablation and transgenic expression studies strongly support the
      concept that beta-catenin together with Lef/Tcf factors act as a switch to
      determine cell fate and promote cell survival and proliferation at several stages
      during mammary gland development. Mice expressing the negative regulator of
      Wnt/beta-catenin signaling (K14-Dkk) fail to form mammary buds, and those lacking
      Lef-1 show an early arrest in this process at stage E13.5. Stabilized
      deltaN89beta-catenin initiates precocious alveologenesis during pubertal
      development, and negative regulators of endogenous beta-catenin signaling
      suppress normal alveologenesis during pregnancy. Stabilized beta-catenin induces
      hyperplasia and mammary tumors in mice. Each of the beta-catenin-induced
      phenotypes is accompanied by upregulation of the target genes cyclin D1 and c
      myc. Cyclin D1, however, is dispensable for tumor formation and the initiation of
      alveologenesis but is essential for later alveolar expansion.

PMID- 14635792
TI  - Role of homeobox genes in normal mammary gland development and breast
      tumorigenesis.
AB  - The role of homeobox-containing genes in embryogenesis and organogenesis is well
      documented. Also, a sizeable body of evidence has accumulated and supports the
      fact that homeobox genes, when dysregulated, are involved in tumorigenesis.
      However, the precise mechanisms of homeobox gene functions are largely unknown.
      The mammary gland, in which most maturation occurs postnatally, provides an ideal
      model for studying the functions of homeobox genes in both development and
      tumorigenesis. The expression of many homeobox genes has been detected in both
      normal mammary gland and neoplastic breast tissues. In the normal mammary gland,
      the expression of homeobox genes is coordinately regulated by hormone and
      extracellular matrix (ECM) and other unknown factors in a spatial and temporal
      manner in both stromal and epithelial cells. Animals with misexpressed homeobox
      genes displayed different extents of defects in ductal proliferation, side
      branching, and alveoli formation, implying that homeobox genes are important for
      normal mammary gland development. Recent studies of homeobox genes in breast
      cancer cells and primary tumors indicate that they may also play a contributory
      or causal role in tumorigenesis by regulating the cell cycle, apoptosis,
      angiogenesis, and/or metastasis.

PMID- 14635793
TI  - Function of PEA3 Ets transcription factors in mammary gland development and
      oncogenesis.
AB  - The Ets gene families of mice and man currently comprise 27 genes that encode
      sequence-specific transcription factors. Ets proteins share an approximately 85
      amino acid structurally conserved ETS DNA binding domain. Genetic analyses in
      model organisms suggest roles for Ets proteins in embryonic development and
      various adult physiological processes. Chromosomal translocations involving
      several ETS genes are associated with Ewing's sarcomas and leukemias, whereas the
      overexpression of some ETS genes is linked with numerous malignancies, including
      breast cancer. Indeed PEA3, ETS-1, PDEF, and ELF-3 transcripts have all been
      reported to be elevated in human breast tumors. Some of the ETS genes that are
      overexpressed in human breast tumors are also overexpressed in mouse models of
      this disease. Notably, pea3, as well as its close paralogs er81 and erm, which
      comprise the pea3 subfamily of ets genes, are coordinately overexpressed in mouse
      mammary tumors. Genetic analyses in mice reveal required roles for one or more of
      the PEA3 subfamily Ets proteins in the initiation and progression of mouse
      mammary tumors. The pea3 subfamily genes are normally expressed in the primitive
      epithelium of mouse mammary buds during embryogenesis, and these three genes are
      expressed in epithelial progenitor cells during postnatal mammary gland
      development. Loss-of-function mutations in the mouse pea3 gene results in
      increased numbers of terminal end buds and an increased fraction of proliferating
      cells in these structures, suggesting a role for PEA3 in progenitor cell renewal
      or terminal differentiation. Taken together these observations suggest that the
      PEA3 subfamily proteins play key regulatory roles in both mammary gland
      development and oncogenesis.

PMID- 14635794
TI  - The role of C/EBPbeta in mammary gland development and breast cancer.
AB  - The CCAAT/enhancer binding protein (C/EBP) family of bZIP transcription factors
      control the proliferation and differentiation of a variety of tissues. While
      C/EBPalpha and -delta are also expressed in the mammary gland, the multiple
      protein isoforms of C/EBPbeta appear to play a critical role in mammary gland
      development and breast cancer. Targeted deletion of all the C/EBPbeta isoforms
      results in a severe inhibition of lobuloalveolar development and a block to
      functional differentiation, as well as more subtle changes in ductal
      morphogenesis. The altered expression of a number of molecular markers, including
      the progesterone, estrogen, and prolactin receptors, the transporter proteins
      (NKCC1 and aquaporin 5), and several markers of skin differentiation (Sprr2A and
      keratin 6), suggests that germline deletion of C/EBPbeta results in an altered
      cell fate. Thus, C/EBPbeta appears to play a role in the specification of
      progenitor cell fate not only in the mammary gland, but also in a number of other
      tissues.

PMID- 14635795
TI  - Progesterone receptors in mammary gland development and tumorigenesis.
AB  - The steroid hormone, progesterone (P), is a central coordinator of all aspects of
      female reproductive activity and plays a key role in pregnancy-associated mammary
      gland morphogenesis and mammary tumorigenesis. The effects of P on the mammary
      gland are mediated by two structurally and functionally distinct nuclear
      receptors PR-A and PR-B that arise from a single gene. Null mutation of both
      receptors in PR knockout (PRKO) mice has demonstrated a critical role for PRs in
      mediating pregnancy-associated mammary ductal branching and lobuloalveolar
      differentiation and in initiation of mammary tumors in response to carcinogen.
      Analysis of the molecular genetic pathways disrupted in PRKO mice has recently
      yielded important insights into the molecular mechanisms of regulation of mammary
      gland morphogenesis by PRs. In addition to its essential role in regulating
      proliferative and differentiative responses of the adult mammary gland during
      pregnancy, P plays a critical role in the protection against mammary
      tumorigenesis afforded by early parity. Thus, the effects of P on postnatal
      developmental plasticity of the mammary gland differ between young and adult
      glands. This review will summarize recent advances in our understanding of 1) the
      molecular mechanisms by which PRs mediate pregnancy-associated mammary gland
      morphogenesis, 2) the role of PRs in mediating tumorigenic responses of the adult
      mammary gland to carcinogen, and 3) the role of P in long-term protection of the
      juvenile mammary gland against tumorigenesis. In addition, we will summarize
      recent insights into the isoform selective contributions to some of these
      activities of PRs obtained from comparative analysis of P-dependent mammary gland
      development in PR isoform specific knockout mice lacking either the PR-A (PRAKO)
      or PR-B (PRBKO).

PMID- 14635796
TI  - NF-kappaB in mammary gland development and breast cancer.
AB  - Nuclear factor of kappaB (NF-kappaB) is a group of sequence-specific
      transcription factors that is best known as a key regulator of the inflammatory
      and innate immune responses. Recent studies of genetically engineered mice have
      clearly indicated that NF-kappaB is also required for proper organogenesis of
      several epithelial tissues, including the mammary gland. Mice have shown severe
      lactation deficiency when NF-kappaB activation is specifically blocked in the
      mammary gland. In addition, there are strong suggestions that NF-kappaB may play
      an important role in the etiology of breast cancer. Elevated NF-kappaB DNA
      binding activity is detected in both mammary carcinoma cell lines and primary
      human breast cancer tissues.

PMID- 14635799
TI  - Seasonal changes in the lower jaw skeleton in male Atlantic salmon (Salmo salar
      L.): remodelling and regression of the kype after spawning.
AB  - The return of Atlantic salmon (Salmon salar) to their home river for spawning
      coincides with drastic skeletal alterations in both sexes. Most prominent is the
      development of a kype (hook) at the tip of the lower jaw in males. Salmon that
      survive spawning have to cope with the kype throughout their life, unless it
      disappears after spawning, as was suggested in the early literature. To
      understand the fate of the kype skeleton, we compared morphological and
      histological features of kypes from pre-spawned mature anadromous males (grilse)
      with post-spawned males (kelts). The kype of male grilse is supported by fast
      growing skeletal needles that differ from regular dentary bone. In kelts, growth
      of the kype skeleton has stopped and skeletal needles are resorbed apically by
      osteoclasts. Simultaneously, and despite the critical physiological condition of
      the animals, proximal parts of the kype skeleton are remodelled and converted
      into regular dentary bone. Apical resorption of the skeleton explains reports of
      a decrease of the kype in kelts. The conversion of basal kype skeleton into
      regular dentary bone contributes to the elongation of the dentary and probably
      also to the development of a larger kype in repetitive spawning males.

PMID- 14635797
TI  - Helix-loop-helix proteins in mammary gland development and breast cancer.
AB  - The basic helix-loop-helix (bHLH) family of transcription factors functions in
      the coordinated regulation of gene expression, cell lineage commitment, and cell
      differentiation in most mammalian tissues. Helix-loop-helix Id (Inhibitor of DNA
      binding) proteins are distinct from bHLH transcription factors in that they lack
      the basic domain necessary for DNA binding. Id proteins thus function as dominant
      negative regulators of bHLH transcription factors. The inhibition of bHLH factor
      activity by forced constitutive expression of Id proteins is closely associated
      with the inhibition of differentiation in a number of different cell types,
      including mammary epithelial cells. Moreover, recent literature suggests
      important roles of HLH proteins in many normal and transformed tissues, including
      mammary gland. Therefore, future directions for prognosis or therapeutic
      treatments of breast cancer may be able to exploit bHLH and Id genes as useful
      molecular targets. The purpose of this review is to summarize the evidence
      implicating HLH proteins in the regulation of normal and transformed mammary
      epithelial cell phenotypes.

PMID- 14635798
TI  - The Nuclear Factor I (NFI) gene family in mammary gland development and function.
AB  - Mammary gland development and function require the coordinated spatial and
      temporal expression of a large fraction of the mammalian genome. A number of site
      specific transcription factors are essential to achieve the appropriate growth,
      branching, expansion, and involution of the mammary gland throughout early
      postnatal development and the lactation cycle. One family of transcription
      factors proposed to play a major role in the mammary gland is encoded by the
      Nuclear Factor I (NFI) genes. The NFI gene family is found only in multicellular
      animals, with single genes being present in flies and worms and four genes in
      vertebrates. While the NFI family expanded and diversified prior to the evolution
      of the mammary gland, it is clear that several mammary-gland specific genes are
      regulated by NFI proteins. Here we address the structure and evolution of the NFI
      gene family and examine the role of the NFI transcription factors in the
      expression of mammary-gland specific proteins, including whey acidic protein and
      carboxyl ester lipase. We discuss current data showing that unique NFI proteins
      are expressed during lactation and involution and suggest that the NFI gene
      family likely has multiple important functions throughout mammary gland
      development.

PMID- 14635800
TI  - The highly specialized vocal tract of the male Mongolian gazelle (Procapra
      gutturosa Pallas, 1777--Mammalia, Bovidae).
AB  - The entire head and neck of a wild adult male Mongolian gazelle (Procapra
      gutturosa) was dissected with special reference to its enlarged larynx. Two
      additional adult male specimens taken from the wild were analysed by computer
      tomography. The sternomandibularis, omohyoideus, thyrohyoideus and
      hyoepiglotticus muscles are particularly enlarged and improve laryngeal
      suspension and stabilization. The epiglottis is exceptionally large. A permanent
      laryngeal descent is associated with the evolution of an unpaired palatinal
      pharyngeal pouch. A certain momentary descent seems to occur during vocalization.
      The high lateral walls of the thyroid cartilage are ventrally connected by a
      broad keel. The large thyroarytenoid muscle is divided into two portions: a
      rostral ventricularis and a caudal vocalis muscle. A paired lateral laryngeal
      ventricle projects between these two muscles. The massive vocal fold is large and
      lacks any rostrally directed flexible structures. It is supported by a large
      cymbal-like fibroelastic pad. Vocal tract length was measured in the course of
      dissection and in computer tomographic images. Two representative spectrograms,
      one of an adult male and one of a juvenile, recorded in the natural habitat of
      the Mongolian gazelle are presented. In the spectrograms, the centre frequency of
      the lowest band is about 500 Hz in the adult male and about 790 Hz in the
      juvenile. The low pitch of the adult male's call is ascribed to the evolutionary
      mass increase and elongation of the vocal folds. In the habitat of P. gutturosa a
      call with a low pitch and, thus, with an almost homogeneous directivity around
      the head of the vocalizing animal may be optimally suited for multidirectional
      advertisement calls during the rut. The signal range of an adult male's call in
      its natural habitat can therefore be expected to be larger than the high-pitched
      call of a juvenile.

PMID- 14635801
TI  - Observations on the vomeronasal organ of prenatal Tarsius bancanus borneanus with
      implications for ancestral morphology.
AB  - Adult primates have at least five known phenotypes of vomeronasal organ (VNO),
      ranging from the typical morphology seen in most other mammals to complete
      absence. With such morphological disparity, the phylogenetic value and any
      inferences on ancestral VNO morphology of the primate VNO are left uncertain. The
      present study investigated the VNO of embryonic and fetal Tarsius bancanus
      borneanus (n = 4) in comparison with prenatal specimens from four other species
      of primates in an effort to clarify adult morphological variations. In all except
      one of the fetal primates, the VNO communicated to the nasopalatine duct. One
      exception occurred in the largest fetal Tarsius (25 mm crown-rump length), in
      which the VNO communicated with the nasal cavity alone. The vomeronasal
      neuroepithelium was well differentiated from a thinner, non-sensory epithelium in
      all Tarsius and New World monkeys studied, as well as late embryonic and fetal
      Microcebus myoxinus. In anterior sections, this neuroepithelium was found in a
      more superior location in Tarsius and New World monkeys compared with Microcebus
      myoxinus. In all primates, masses of cell bodies were found superior to the VNO,
      intermingled with nerve fibres. These morphologically resembled luteinizing
      hormone-releasing hormone neurons described in other mammals, including humans,
      suggesting that a primitive association of these neurons with the VNO may exist
      in all primate taxa. The present study revealed that prenatal similarities exist
      in Tarsius and New World primates in VNO epithelial morphology. However, these
      are transient stages of morphology. If tarsiers and anthropoids do represent a
      clade (Haplorhini), then the atypical morphology seen in adult tarsiers and New
      World monkeys probably represents the adult VNO morphology of a haplorhine common
      ancestor.

PMID- 14635802
TI  - Microscopic analysis of the cellular events during scatter factor/hepatocyte
      growth factor-induced epithelial tubulogenesis.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF), a large multifunctional
      polypeptide growth and motility factor, is known to play important roles during
      embryonic development, adult tissue growth and repair. In an established three
      dimensional type I collagen model, SF/HGF induces Madin-Darby canine kidney
      (MDCK) epithelial cysts to form long, branching tubules (tubulogenesis). In
      addition, the composition of the surrounding extracellular matrix (ECM) has been
      shown to modulate SF/HGF-induced morphogenesis, where tubulogenesis was
      completely abrogated in Matrigel basement membrane. Many cellular events that
      occur during SF/HGF-mediated remodelling, and its modulation by the ECM, remain
      unclear. We have investigated these mechanisms through microscopic examination of
      the time-course of SF/HGF-induced responses in MDCK cysts cultured in type I
      collagen or Matrigel. We found that early responses to SF/HGF were matrix
      independent. Changes included increased paracellular spacing between normally
      closely apposed lateral membranes, and the formation of filopodial processes,
      indicating a partial motile response. Cell-cell contact was maintained, with the
      persistence of cell junctions. Therefore, while one or a number of ECM components
      are preventing SF/HGF-primed cells from undergoing an invasive and/or migratory
      programme, non-permissive matrices are not preventing SF/HGF signalling to the
      cell. Later matrix-dependent responses, which occurred in type I collagen but not
      Matrigel, included the formation of basal protrusions that comprise two or more
      neighbouring cells, which extend to form nascent tubules. Modified polarity of
      cells comprising the basal protrusions was evident, with a marker for the apical
      membrane being found in the same region as adherens junctions and desmosomes,
      typically localized at lateral membranes. We propose a model for SF/HGF-induced
      tubulogenesis in which tubules form from basal protrusions of adjacent cells.
      This mechanism of in vitro tubule formation has many similarities to reported in
      vivo epithelial tubulogenesis.

PMID- 14635803
TI  - Expression of fibroblast growth factor-2 (FGF-2) in early stages (days 3-11) of
      the development of the avian lung, Gallus gallus variant domesticus: an
      immunocytochemical study.
AB  - In the avian lung, the bronchial system forms from epithelial (endodermal) cells.
      The intrapulmonary primary bronchus is the focal point of airway development. It
      originates secondary bronchi (SB) along its proximal-distal extent and
      parabronchi (tertiary bronchi) arise from and connect the SB. From as early as
      day 3.5, fibroblast growth factor-2 (FGF-2) is diffusely expressed in the
      epithelial and mesenchymal cells. Up-regulation of FGF-2 in discrete areas of the
      developing lung seem to set the growth rate, trajectories followed, areas
      appropriated, three-dimensional symmetry and coupling of the airways. Expressed
      early in development and persisting into the incubation period, FGF-2 may be
      involved in the formation of the avian lung. Morphogenetic differences between
      the avian and the mammalian lungs may explain the existing structural
      contrarieties.

PMID- 14635804
TI  - Postnatal development of the basolateral complex of rabbit amygdala: a
      stereological and histochemical study.
AB  - The aim of the study was to estimate developmental changes in the rabbit
      basolateral complex (BLC) by stereological and histochemical methods. Material
      consisted of 45 brains of New Zealand rabbits (aged from 2 to 180 days, P2 to
      P180) of both sexes, divided into nine groups. The following parameters were
      estimated: volume of the cerebral hemisphere; volume of the whole BLC and of
      particular BLC nuclei; neuronal density and total number of neurons in these
      nuclei. Developmental changes in acetylcholinesterase (AChE) activity in the BLC
      were also examined. The volume of the cerebral hemisphere increased until P30,
      whereas volumes of nuclei increased for longer--until P90. The density of neurons
      in all nuclei studied reached the level characteristic for an adult animal at
      about P30. The total number of neurons in the dorsolateral division of the
      lateral nucleus (Ldl) stabilized the earliest--between P30 and P60, whereas in
      the ventromedial division of the lateral nucleus (Lvm), basomedial (BM) and
      basolateral (BL) nuclei the number stabilized later--between P60 and P90. AChE
      activity appears minimal in the BLC on P2, reaches a maximum on P30 and then
      decreases to the level characteristic of an adult animal on P60. AChE activity
      was greater in BL than in other nuclei in all age groups. Reaching adult AChE
      activity 1 month earlier than the total number of neurons in the BLC may indicate
      a role of the cholinergic system in BLC maturation.

PMID- 14635805
TI  - Histochemical analysis of lymphatic endothelial cells in the pancreas of non
      obese diabetic mice.
AB  - We studied the relationship between insulitic development and function-structural
      changes of pancreatic lymphatics in non-obese diabetic (NOD) mice using combined
      5'-nucleotidase (5'-Nase) enzyme histochemical and secondary lymphoid tissue
      chemokine (SLC/CCL21) immunohistochemical methods. Interlobular lymphatic vessels
      were positive for 5'-Nase throughout the pancreas, and dependent on both blood
      vessels and pancreatic ducts. Intralobular initial lymphatics were rare and
      occasionally ran in the neighbourhood of islets. During the non-insulitic stage,
      the 5'-Nase-reactive product was evenly distributed on the surface of lymphatic
      endothelial cells (LECs) with weak expression of CCL21. The activity of 5'-Nase
      on lymphatic vessels became slightly reduced as insulitis developed. The
      increasing blood glucose values appeared to be consistent with an increasing
      CCL21 expression by the endothelial lining, especially on the surface of LECs
      adjacent to the infiltrated islets and tissues. Lymphocytes and dendritic cells
      (DCs) were frequently located in the connective tissue, surrounding the lymphatic
      wall with deposition of 5'-Nase precipitates. As the infiltration became severe,
      lymphocytes and DCs accumulated within lymphatic vessels and expressed high
      levels of CCL21. The most significant finding was that many DCs adhered to
      lymphatic vessels, transmigrating via the thin and indented endothelial walls.
      The activity of 5'-Nase was increased on the adhesion surface between DCs (or
      lymphocytes) and LECs. The latter were characterized by open intercellular
      junctions and obvious cytoplasmic protrusions. These results suggest that LECs
      closely interact with DCs and lymphocytes, and play a key role in the migration
      of DCs and lymphocytes via lymphatic vessels during the pathological processes of
      insulitis in NOD mice.

PMID- 14635806
TI  - Morphogenesis of the human lacrimal gland.
AB  - The aim of this study was to determine the main stages of the lacrimal gland's
      developmental process in humans and to establish its precise morphogenetic
      timetable. Its onset is generally assumed to take place at O'Rahilly's stage 21,
      arising from an epithelial thickening of the superior extreme of the temporary
      conjunctival fornix. However, the present study points to a prior stage in the
      process: the presence of epithelial-mesenchymal changes in embryos at O'Rahilly's
      stage 19. The study was performed using light microscopy on serial sections of 37
      human specimens: 23 embryos and 14 fetuses ranging from 15 to 137 mm crown-rump
      length (7-116 weeks of development). Three stages in lacrimal gland morphogenesis
      were identified: (1) the presumptive glandular stage, O'Rahilly's stages 19-20,
      characterized by a thickening of the superior fornix epithelium together with
      surrounding mesenchymal condensation; (2) the bud stage, generally assumed to be
      the first manifestation of glandular origin, characterized initially by the
      appearance of nodular formations in the region of the superior conjunctival
      fornix and concluding with the appearance of lumina within the epithelial buds;
      and (3) the glandular maturity stage, weeks 9-16, the period in which the gland
      begins to take on the morphology of adulthood.

PMID- 14635807
TI  - Cannibalism among phytoseiid mites: a review.
AB  - Cannibalism, the killing and consumption of conspecific individuals, is a common
      and widespread phenomenon in the animal kingdom. Cannibalism in phytoseiid mites
      has been known for decades but until recently reports were mainly observational
      and experimental data were lacking. Recently, diverse aspects of cannibalism,
      such as life stage-related cannibalism and preference, nutritional benefits, the
      role of diet specialization, species discrimination, and kin discrimination were
      assessed and compared within and among diverse phytoseiid species. As a result,
      species of the family Phytoseiidae provide a rather well studied group with
      respect to cannibalism at the individual level. The present review aims at
      summarizing and canalizing the wealth of recent experimental data on
      cannibalistic phytoseiid mites and seeks to emphasize and discuss the behavioral
      and ecological significance of cannibalism. In an ideal case, it will stimulate
      studies on topics related to cannibalism that are currently underrepresented such
      as the consequences of cannibalism for population dynamics and species
      composition in a given habitat. Partitioned in six sections, the key determinants
      of cannibalism in phytoseiid mites are treated by extracting features that are
      common among species and, where applicable, by indicating the circumstances that
      minimize the costs and maximize the benefits of cannibalism.

PMID- 14635808
TI  - Leaf pubescence mediates the abundance of non-prey food and the density of the
      predatory mite Typhlodromus pyri.
AB  - Plants with leaves having numerous trichomes or domatia frequently harbor greater
      numbers of phytoseiid mites than do plant with leaves that lack these structures.
      We tested the hypothesis that this pattern occurs, in part, with Typhlodromus
      pyri because trichomes increase the capture of pollen or fungal spores that serve
      as alternative food. Using a common garden orchard, we found that apple varieties
      with trichome-rich leaves had 2-3 times more pollen and fungal spores compared to
      varieties with trichome-sparse leaves. We also studied the effects of leaf
      trichome density and pollen augmentation on T. pyri abundance to test the
      hypothesis that leaf trichomes mediate pollen and fungal spore capture and
      retention and thereby influence phytoseiid numbers. Cattail pollen (Typha sp.)
      was applied weekly to mature 'McIntosh' and 'Red Delicious' trees grown in an
      orchard and, in a separate experiment, to potted trees of the same varieties.
      'McIntosh' trees have leaves with many trichomes whereas leaves on the 'Red
      Delicious' trees have roughly half as many trichomes. With both field-grown and
      potted trees, adding cattail pollen to 'Red Delicious' trees increased T. pyri
      numbers compared to 'Red Delicious' trees without pollen augmentation. In
      contrast, cattail pollen augmentation had no effect on T. pyri populations on
      'McIntosh' trees. Augmentation with cattail pollen most likely supplemented a
      lower supply of naturally available alternative food on 'Red Delicous' leaves and
      thereby enhanced predator abundance. These studies indicate that larger
      populations of T. pyri on pubescent plants are due, in part, to the increased
      capture and retention of pollen and fungal spores that serve as alternative
      foods.

PMID- 14635809
TI  - Exudate from sporulating cultures of Hirsutella thompsonii inhibit oviposition by
      the two-spotted spider mite Tetranychus urticae.
AB  - The acaricidal mycopathogen Hirsutella thompsonii has been found to secrete
      metabolites that are active against female Tetranychus urticae. Specifically, the
      rose-colored exudate produced on sporulating cultures of Mexican HtM120I strain
      sterilized female spider mites in a dose-dependent fashion. Topical application
      of the exudate resulted in a 100% reduction in mite fecundity over the initial
      six days of experimentation. Depending upon the exudate dosage, mites partially
      recovered within 3 and 6 d post-treatment and produced a limited number of eggs.
      The spider mite active HtM120I exudate contained less detectable HtA toxin than
      the HtM120I broth filtrate, and it was innocuous when injected into the greater
      wax moth Galleria mellonella L. larvae. Broth filtrates of HtM120I cultures,
      although toxic to assayed G. mellonella larvae, did not inhibit mite oviposition
      to the degree or duration of the exudate preparations. These findings suggest
      that the factor responsible for suppressing oviposition in female spider mites is
      linked to the sporulation process and is distinct from the well-characterized HtA
      produced by vegetative cells.

PMID- 14635810
TI  - Population dynamics of Panonychus osmanthi (Acari: Tetranychidae) on two
      Osmanthus species.
AB  - Panonychus osmanthi is a non-diapausing species of spider mite that superficially
      resembles P. citri. It infests Osmanthus species, which are evergreen roadside
      and garden trees. The population dynamics of P. osmanthi were studied on
      Osmanthus aurantiacus and O. x fortunei during a three-year period. Seasonal
      changes in P. osmanthi populations were fundamentally the same in each year,
      although their density differed greatly from year to year. The P. osmanthi
      population was bimodal, with one peak in spring (May-June) and another in winter
      (November-January). Populations abruptly declined after the spring peak.
      Predators showed a delayed density-dependent response to changes in spider mites
      from spring to summer, whereas in autumn and winter, predators were few because
      they had entered diapause. To determine the effect of predators on the rapid
      decline of spider mites just after the spring peak, the predators were removed by
      treating the trees with a synthetic pyrethroid. As a result, spider mite density
      did not decline after the spring peak and remained at a high level during the
      June-August period when spider mite density is usually very low. This suggests
      that predators play an important role in the drastic decline of P. osmanthi
      density just after the spring peak.

PMID- 14635811
TI  - Life-history traits of the six Panonychus species from Japan (Acari:
      Tetranychidae).
AB  - Six species of the genus Panonychus are known from Japan. Life-history parameters
      of all six species were investigated at 25 degrees C, and for three species two
      strains of different geographical origin were included. The intrinsic rate of
      natural increase (r(m)) ranged from 0.172/day for the P. osmanthi albino strain
      to 0.209/day for P. citri, while the net reproductive rate (R0) varied from 23.98
      in the thelytokous species P. thelytokus to 46.61 in P. citri. Both values were
      higher in the polyphagous species (P. ulmi, P mori and P. citri), which are
      considered crop pests, than those in the oligophagous species (P. thelytokus and
      P. osmanthi), considered non-pests. The only exception was P. bambusicola, an
      oligophagous non-pest species with R0- and r(m)-values closely resembling those
      of the three polyphagous species.

PMID- 14635812
TI  - Sorting out the effects of Wolbachia, genotype and inbreeding on life-history
      traits of a spider mite.
AB  - Wolbachia bacteria manipulate host reproduction by inducing cytoplasmic
      incompatibility (CI) and sex ratio distortion. Wolbachia are transmitted from
      mother to offspring through the cytoplasm of the egg. Therefore, reproduction of
      Wolbachia is tightly coupled to reproduction of its host. Mathematical analysis
      predicts that in the course of evolution, traits that reduce the physiological
      costs of the infection will be selectively favored. For a Wolbachia-host system
      to evolve, traits under selection must have some genetic component and variation
      must be present in the population. We have previously established that highly
      inbred isofemale lines of the two-spotted spider mite Tetranychus urticae may
      differ regarding the effects of infection by Wolbachia, and that at least some of
      the traits affected had a genetic component. However, the effects measured could
      have been affected by the fact that the lines were severely inbred prior to the
      experiments. In this paper we attempt to distinguish between the effects of
      Wolbachia, isofemale line, and inbreeding. We show that Wolbachia did not affect
      longevity but infected females produced smaller clutch sizes, more daughter
      biased sex ratios and had decreased F1 mortality; between-line variation was
      found for clutch size, F1 mortality and sex ratio; finally, inbreeding resulted
      in an overall reduction of clutch sizes, and a change in survival curves and mean
      longevity.

PMID- 14635813
TI  - Radiation in sexual and parthenogenetic oribatid mites (Oribatida, Acari) as
      indicated by genetic divergence of closely related species.
AB  - The D3 domain and its flanking regions of 28S rRNA of four pairs of closely
      related sexual species (Eupelops hirtus and E. torulosus; Oribatella calcarata
      and O. quadricornuta; Chamobates voigtsi and Ch. borealis; Liacarus coracinus and
      L. subterraneus) and four pairs of closely related parthenogenetic species
      (Nanhermannia nana and Na. coronata; Nothrus silvestris and No. palustris;
      Tectocepheus sarekensis and T. minor; Camisia spinifer and Ca. segnis) of
      oribatid mites were sequenced to investigate (1) if the D3 region can be used as
      a species marker and (2) if there is genetic variation among closely related
      species pairs and if its magnitude is related to reproductive mode. Furthermore,
      we investigated the world-wide genetic variation of the D3 region from the
      oribatid mite species Platynothrus peltifer. There was no intraspecific genetic
      variation in the D3 region in any of the species studied; it was even identical
      in two closely related parthenogenetic species (Na. nana and Na. coronata) and
      two closely related sexual species (E. hirtus and E. torulosus). The genetic
      differences of the other species pairs indicated that both parthenogenetic and
      sexual lineages have various ages. On average, however, the differences between
      the closely related parthenogenetic species were larger than those between
      closely related sexual species, indicating that parthenogenetic lineages exist
      historically and may radiate slower than sexual species. The findings of this
      study support the hypothesis that some of the parthenogenetic oribatid mite taxa
      (Tectocepheus, Nothrus) are 'ancient asexuals'. The absence of intraspecific or
      intra-individual variation in the D3 region of parthenogenetic species is
      consistent with the presence of concerted evolution in the 28S rRNA gene. From
      this we infer the existence of a meiotic process, which is consistent with the
      automixy known from several other parthenogenetic oribatid species.

PMID- 14635814
TI  - Chemical ecology of oribatid mites III. Chemical composition of oil gland
      exudates from two oribatid mites, Trhypochthoniellus sp. and Trhypochthonius
      japonicus (Acari: Trhypochthoniidae).
AB  - The composition of oil gland exudates from two oribatid mites, Trhypochthoniellus
      sp. and Trhypochthonius japonicus, was studied with reference to the related
      species Trhypochthoniellus crassus. Trhypochthoniellus sp. contained a mixture of
      seven compounds; (Z,Z)-6,9-heptadecadiene, geranial, 3-hydroxybenzene-1,2
      dicarbaldehyde (gamma-acaridial), neryl formate, neral, (Z)-8-heptadecene and
      geranyl formate in decreasing order of abundance. The profile of the components
      from T. japonicus consisted of two types depending on the locality of sampling
      with unknown reason; one possessing a mixture of eight compounds [(Z,E)-farnesal,
      gamma-acaridial, (Z,Z)-6,9-heptadecadiene, (E,E)-farnesal, (Z)-8-heptadecene and
      geranial in decreasing order] together with two unknown compounds, and the other
      composed of the same set of compounds together with 2-hydroxy-6
      methylbenzaldehyde as the most abundant component. Relative abundance among
      common components was consistent between the two types of T. japonicus. Profiles
      of components differed among three species including T. crasus. The phylogenetic
      relationship between Oribatida and Astigmata was discussed based on secretory
      compounds commonly distributed between these two suborders.

PMID- 14635815
TI  - Distribution of deformed wing virus within honey bee (Apis mellifera) brood cells
      infested with the ectoparasitic mite Varroa destructor.
AB  - The distribution of deformed wing virus (DWV) in adult female Varroa destructor
      and in their progeny in relation to the pupal host bee was investigated to
      evaluate acquisition and transfer of DWV by the mites. The results clearly show
      that adult female mites regularly act as competent vectors of DWV, however, they
      do not acquire or transfer virus on all possible occasions. Mother mites may
      contain DWV while the pupal host remains free from overt infection and both
      mother mites and mite progeny may not acquire detectable amounts of DWV from an
      infected host bee. However, a majority of mites feeding on pupae that emerge with
      deformed wings will contain DWV. The data also demonstrates that both adult and
      immature mite progeny most likely acquire DWV from DWV-infected host bees and not
      from their mother mites. Possible explanations for the obtained results are
      discussed.

PMID- 14635816
TI  - The effects of temperature and dose of formic acid on treatment efficacy against
      Varroa destructor (Acari: Varroidae), a parasite of Apis mellifera (Hymenoptera:
      Apidae).
AB  - In order to decrease the variability of formic acid treatments against the honey
      bee parasite the varroa mite, Varroa destructor (Anderson and Trueman 2000), it
      is necessary to determine the dose-time combination that best controls mites
      without harming bees. The concentration x time (CT) product is a valuable tool
      for studying fumigants and how they might perform under various environmental
      conditions. This laboratory study is an assessment of the efficacy of formic acid
      against the varroa mite under a range of formic acid concentrations and
      temperatures. The objectives are 1) to determine the effect of temperature and
      dose of formic acid on worker honey bee and varroa mite survival, 2) to determine
      the CT50 products for both honey bees and varroa mites and 3) to determine the
      best temperature and dose to optimize selectivity of formic acid treatment for
      control of varroa mites. Worker honey bees and varroa mites were fumigated at 0,
      0.01, 0.02, 0.04, 0.08, and 0.16 mg/L at 5, 15, 25, and 35 degrees C for 12 d.
      Mite and bee mortality were assessed at regular intervals. Both mite and bee
      survival were affected by formic acid dose. Doses of 0.08 and 0.16 mg/L were
      effective at killing mites at all temperatures tested above 5 degrees C. There
      was a significant interaction between temperature, dose, and species for the CT50
      product. The difference between the CT50 product of bees and mites was
      significant at only a few temperature-dose combinations. CT product values showed
      that at most temperatures the greatest fumigation efficiency occurred at lower
      doses of formic acid. However, the best fumigation efficiency and selectivity
      combination for treatments occurred at a dose of 0.16 mg/L when the temperature
      was 35 degrees C.

PMID- 14635818
TI  - The fossil record and the origin of ticks (Acari: Parasitiformes: Ixodida).
AB  - Ticks are obligate hematophagous ectoparasites of terrestrial vertebrates.
      Hypotheses on the origin of ticks have been proposed based on tick-host
      associations and the total-evidence approach analysis of morphological and
      molecular characters. Nevertheless, the origin of ticks remains a controversial
      issue. Here, I revised the tick fossil record including reports from the
      literature and the description of 7 new specimens. The analysis of fossil ticks
      provides few clues to tick evolution but does not contradict recent hypotheses
      based on total-evidence approach analysis that place the origin of ticks in the
      Cretaceous (65-146 mya) with most of the evolution and dispersal occurring during
      the Tertiary (5-65 mya).

PMID- 14635817
TI  - The effect of sub-floor heating on house-dust-mite populations on floors and in
      furniture.
AB  - It is well known that dehydrating conditions for house dust mites can be created
      by simply raising the temperature, causing loss of body water and eventually
      death. Thus, it can be expected that conditions for dust mites are less
      favourable on floors supplied with sub-floor heating. This was examined in a
      study of 16 houses with sub-floor heating and 21 without. The pattern of changes
      in air humidity and temperature on the floors was investigated and compared to
      known data of the tolerance of dust mites. Also the resident mite populations
      were compared. Floors with sub-floor heating had, on average, fewer mites, but
      the difference with unheated floors was small. It was remarkable that mite
      numbers were also lower in upholstered furniture. Another important observation
      was that some houses with sub-floor heating had high mite numbers, indicating
      that this type of heating is compatible with a thriving mite population.
      Temperature and humidity conditions of heated floors may allow mites not only to
      survive, but also to remain active in winter. A moderate increase in temperature,
      a moderate decrease in (absolute) air humidity, or a combination of both, will
      suffice to keep the humidity all winter below the Critical Equilibrium Humidity,
      the level of air humidity that is critical for mite growth and reproduction,
      hence for allergen production. However, it is argued that measures to suppress
      allergen production by house dust mites are likely to be far more effective if
      taken in summer rather than in winter.

PMID- 14635820
TI  - Survival of Theileria parva-infected adult Rhipicephalus appendiculatus under
      laboratory and quasi-natural conditions.
AB  - Adult Rhipicephalus appendiculatus Muguga, having high or low intensities of
      Theileria parva Muguga infection in their salivary glands, were exposed to 20
      degrees C and 85% relative humidity in the laboratory or quasi-natural
      conditions. Survival of the ticks and T. parva infections in their salivary
      glands was then monitored over a two year period. Ticks, having an average
      infection level of 2 infected acini per female, survived for up to 70 or 106
      weeks after moulting under the laboratory or quasi-natural conditions
      respectively. Those having an infection level of 26 infected acini per female,
      survived for a similar duration except that those under quasi-natural conditions
      survived for a slightly shorter duration (102 weeks). Similarly, T. parva
      parasites survived for much longer periods under quasi-natural conditions than
      under the laboratory conditions. They survived for up to 38 or 78 weeks post
      salivary gland infection under the laboratory or quasi-natural conditions
      respectively in both categories of infection levels. There was apparently a
      density dependent relationship in T. parva survival, with a dramatic fall in
      infection occurring in ticks with high levels of infection between weeks 10 and
      18 or weeks 38 and 46 post salivary gland infection in those exposed to
      laboratory or quasi-natural conditions before levelling off.

PMID- 14635821
TI  - Complementary and alternative medicine.

PMID- 14635819
TI  - Evidence of Babesia microti infection in multi-infected Ixodes persulcatus ticks
      in Russia.
AB  - To detect Babesia-infected Ixodes persulcatus Shulze in a suburb of St.
      Petersburg, Russia, 738 adult ticks were studied using Babesia specific primers
      and PCR techniques. The entire sample (more than 1,200 individuals) was screened
      for the presence of Borrelia spp., Ehrlichia spp. and tick-borne encephalitis
      virus (TBEV). All 7 ticks infected with Babesia microti, were also infected with
      other pathogens (all 7 among 417 infected ticks, zero amongst the remaining 321
      naive ones (chi2 = 5.25, p<0.05). Babesia microti occurred twice with Borrelia
      afzelii, 3 times with Borrelia garinii, once with both, and once with both B.
      garinii and TBEV. The prevalence of infection with Borrelia spp. was 34.0%, with
      Ehrlichia spp. 6.2%, with TBEV 1.5%, and with Ba. microti 0.9%. Babesia microti
      infection was not found in combination with Ehrlichia sp. or Borrelia burgdorferi
      sensu stricto. The latter pathogen (prevalence 2.6%), just like Ba. microti, was
      not encountered as a monoinfection. The data suggest that Ba. microti infection
      can only survive in I. persulcatus in combination with Borrelia spp. (7 of 7
      infections). The disease in humans is more severe and longer-lasting when more
      than one pathogen is involved. Our observations show that the well known St.
      Petersburg focus of tick-borne encephalitis and Lyme disease is also a focus of
      ehrlichiosis and babesiosis.

PMID- 14635822
TI  - Clinical pharmacokinetics of morphine.
AB  - Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is
      the standard against which new analgesics are measured. A thorough understanding
      of the pharmacokinetics of morphine is required in order to safely and
      effectively use this analgesic in a wide variety of patients with different
      levels of organ function. A MEDLINE search was conducted to identify literature
      published between 1966 and January 2002 relevant to the pharmacokinetics of
      morphine. These publications were reviewed and the literature summarized
      regarding unique and clinically important elements of morphine disposition
      relative to its parenteral administration (including intravenous, intramuscular,
      subcutaneous, epidural and intrathecal administration), absorption profile
      (immediate release, controlled release, and sublingual/buccal, and rectal
      administration), distribution, and its metabolism/excretion. Special populations,
      including infants, elderly, and those with renal/liver failure, have a unique
      morphine pharmacokinetic profile that must be taken into account in order to
      maximize analgesic efficacy and reduce the risk of adverse events.

PMID- 14635823
TI  - Newer anticonvulsant drugs in neuropathic pain and bipolar disorder.
AB  - Older anticonvulsants have been used to manage both chronic pain and bipolar
      disorders. As the armamentarium of anticonvulsants increases, the role of the
      newer agents for pain or mood disorders is uncertain. This paper summarizes the
      clinical data available with gabapentin, lamotrigine, oxcarbazepine, tiagabine
      and topiramate for bipolar disorder and lamotrigine, oxcarbazepine, tiagabine and
      topiramate for neuropathic pain.

PMID- 14635824
TI  - Pain clinicians' rankings of aberrant drug-taking behaviors.
AB  - A pilot study was conducted to examine experienced pain physicians' perceptions
      of aberrant drug taking behaviors. One hundred pain physicians attending a
      meeting on pain management were asked to rank order (from most aberrant = 1 to
      least aberrant = 13) a list of aberrant drug-taking behaviors. The sample was
      comprised mainly of anesthesiologists (50%) and half of the group had 10 or more
      years of pain management experience. The group prescribed an average of 19-96
      opioid medications per week. Practice variables were not related to the rank
      ordering of the behaviors. All of the various behaviors appeared in all 13 of the
      rank ordering slots, suggesting a great deal of individual difference in the
      perception of these behaviors. By examining the average ranking of the behaviors,
      we noted that physicians' focus on illegal behaviors as the most aberrant
      followed by the alteration of route of delivery and self-escalation of dose. This
      survey suggests that an experienced group of pain clinicians does not view
      aberrant drug related behaviors uniformly. Average rankings suggest clinicians
      seem to view illegal behavior as the most worrisome. These results must be
      interpreted with caution due to the small convenience sample, the lack of data on
      the level of addiction medicine training of the respondents and the lack of data
      on those physicians who chose not to respond. Further inquiry could be used to
      guide clinicians' responses to aberrant behaviors when encountered in patients on
      controlled substances for pain.

PMID- 14635825
TI  - Extemporaneous compounding of pain and symptom control medications.
AB  - This paper introduces a new series in the Journal on extemporaneously compounded
      dosage forms for symptom control. Some advantages and limitations of compounded
      medications are described and issues that clinicians should consider are
      mentioned. Topics that will be discussed in future papers in this series are
      described. Changes of compounding-related chapters of the United States
      Pharmacopeia from advisory statements to enforceable standards are discussed. As
      an example of important formulation considerations, some physical-chemical
      characteristics and route of administration characteristics of opioid analgesics
      are discussed.

PMID- 14635826
TI  - Medications for patient comfort when weaning mechanical ventilation in palliative
      care.
AB  - Indications for mechanical ventilation in end of life care and the place for
      weaning are discussed. Preferred medications to facilitate weaning are short
      acting benzodiazepines. The importance of the environment in which ventilatory
      support is provided is discussed as are ethical issues including patient wishes
      and those of a patient' s proxy.

PMID- 14635827
TI  - The importance of perspective in pharmacoeconomic analyses.
AB  - Readers of pharmacoeconomic analyses should pay attention to the perspective used
      in conducting the analyses because very different costs may be included based on
      the investigators' perspectives. The most common perspectives are those of
      providers, payers, patients, and society. The societal perspective is broadest
      and is usually preferred.

PMID- 14635828
TI  - Extemporaneous compounding: a return to regulatory limbo?
AB  - Extemporaneous compounding of medications has been an integral component of the
      practice of pharmacy and medicine since the practices began. A staple of early
      medical and pharmacy practice, even today many patients benefit from compounding
      at some point in their care. Unfortunately, the regulation of the practice has
      not been so consistent. With a recent decision by the US Supreme Court,
      compounding regulation is again uncertain. This commentary reviews compounding
      practice, the history of compounding regulation, and discusses the current
      regulatory status of the practice.

PMID- 14635829
TI  - The polarized debate over complementary and alternative medicine.
AB  - Debate about the place and scientific of complementary and alternative medicine
      (CAM) has increased markedly in 2002 following the release of the report of the
      White House Commission on Alternative and Complementary Medicine Policy.
      Arguments for and against the integration of CAM into mainstream medicine that
      have been made are discussed. Positions taken by organizations opposed to CAM are
      described as are arguments to study the place of CAM further.

PMID- 14635830
TI  - Resources in The Cochrane Library: Issue number 2, 2002.
AB  - Reviews and protocols relevant to pain management and palliative care that
      appeared in Issue 2 for 2002 of The Cochrane Library are listed.

PMID- 14635831
TI  - Complementary and alternative medicine: information for practitioners and
      consumers.

PMID- 14635832
TI  - Report of the White House Commission on Complementary and Alternative Medicine
      Policy: recommendations and actions.
AB  - The recommendations in the final report of the White House Commission on
      Complementary and Alternative Medicine Policy that was released in March 2002 are
      presented.

PMID- 14635833
TI  - What are dietary supplements?

PMID- 14635834
TI  - The Medicare hospice benefit.

PMID- 14635835
TI  - American Geriatrics Society releases persistent pain management guideline.

PMID- 14635836
TI  - American Pain Society guideline for treatment of arthritis pain.

PMID- 14635837
TI  - MHC studies in nonmodel vertebrates: what have we learned about natural selection
      in 15 years?
AB  - Elucidating how natural selection promotes local adaptation in interaction with
      migration, genetic drift and mutation is a central aim of evolutionary biology.
      While several conceptual and practical limitations are still restraining our
      ability to study these processes at the DNA level, genes of the major
      histocompatibility complex (MHC) offer several assets that make them unique
      candidates for this purpose. Yet, it is unclear what general conclusions can be
      drawn after 15 years of empirical research that documented MHC diversity in the
      wild. The general objective of this review is to complement earlier literature
      syntheses on this topic by focusing on MHC studies other than humans and mice.
      This review first revealed a strong taxonomic bias, whereby many more studies of
      MHC diversity in natural populations have dealt with mammals than all other
      vertebrate classes combined. Secondly, it confirmed that positive selection has a
      determinant role in shaping patterns of nucleotide diversity in MHC genes in all
      vertebrates studied. Yet, future tests of positive selection would greatly
      benefit from making better use of the increasing number of models potentially
      offering more statistical rigour and higher resolution in detecting the effect
      and form of selection. Thirdly, studies that compared patterns of MHC diversity
      within and among natural populations with neutral expectations have reported
      higher population differentiation at MHC than expected either under neutrality or
      simple models of balancing selection. Fourthly, several studies showed that MHC
      dependent mate preference and kin recognition may provide selective factors
      maintaining polymorphism in wild outbred populations. However, they also showed
      that such reproductive mechanisms are complex and context-based. Fifthly, several
      studies provided evidence that MHC may significantly influence fitness, either by
      affecting reproductive success or progeny survival to pathogens infections.
      Overall, the evidence is compelling that the MHC currently represents the best
      system available in vertebrates to investigate how natural selection can promote
      local adaptation at the gene level despite the counteracting actions of migration
      and genetic drift. We conclude this review by proposing several directions where
      future research is needed.

PMID- 14635838
TI  - Modelling the spatial configuration of refuges for a sustainable control of
      pests: a case study of Bt cotton.
AB  - The 'high-dose-refuge' (HDR) strategy is widely recommended by the biotechnology
      industry and regulatory authorities to delay pest adaptation to transgenic crops
      that produce Bacillus thuringiensis (Bt) toxins. This involves cultivating
      nontoxic plants (refuges) in close proximity to crops producing a high dose of Bt
      toxin. The principal cost associated with this strategy is due to yield losses
      suffered by farmers growing unprotected, refuge plants. Using a population
      genetic model of selection in a spatially heterogeneous environment, we show the
      existence of an optimal spatial configuration of refuges that could prevent the
      evolution of resistance whilst reducing the use of costly refuges. In particular,
      the sustainable control of pests is achievable with the use of more aggregated
      distributions of nontransgenic plants and transgenic plants producing lower doses
      of toxin. The HDR strategy is thus suboptimal within the context of sustainable
      agricultural development.

PMID- 14635839
TI  - Large discrepancies in differentiation of allozymes, nuclear and mitochondrial
      DNA loci in recently founded Pacific populations of the pearl oyster Pinctada
      margaritifera.
AB  - This study presents a comparative analysis of population structure applied to the
      pearl oyster (Pinctada margaritifera) from the Central Pacific islands using
      three classes of molecular markers: two mitochondrial genes (mtDNA), five
      anonymous nuclear loci (anDNA), and eight polymorphic allozymes. Very low levels
      of haplotype diversity and nucleotidic divergence detected for mtDNA validate the
      hypothesis of a recent (re)colonization of Polynesian lagoons after their
      exondation during the last glaciations. Some nuclear loci, however, showed highly
      significant FST values, indicating a reduced amount of larval exchange between
      archipelagos at present. A large interlocus variance of FST was nevertheless
      observed. We discuss whether this pattern is inherent to the stochasticity of the
      drift process since recolonization, or if it could result from balancing
      selection acting on certain loci. This study illustrates once more the need to
      combine the analysis of several kinds of loci when unrelated phenomena are likely
      to leave their footprints on genetic structure.

PMID- 14635840
TI  - Genetic polymorphism and trade-offs in the early life-history strategy of the
      Pacific oyster, Crassostrea gigas (Thunberg, 1795): a quantitative genetic study.
AB  - We investigated genetic variability and genetic correlations in early life
      history traits of Crassostrea gigas. Larval survival, larval development rate,
      size at settlement and metamorphosis success were found to be substantially
      heritable, whereas larval growth rate and juvenile traits were not. We identified
      a strong positive genetic correlation between larval development rate and size at
      settlement, and argue that selection could optimize both age and size at
      settlement. However, trade-offs, resulting in costs of metamorphosing early and
      large, were suggested by negative genetic correlations or covariances between
      larval development rate/size at settlement and both metamorphosis success and
      juvenile survival. Moreover, size advantage at settlement disappeared with time
      during the juvenile stage. Finally, we observed no genetic correlations between
      larval and juvenile stages, implying genetic independence of life-history traits
      between life-stages. We suggest two possible scenarios for the maintenance of
      genetic polymorphism in the early life-history strategy of C. gigas.

PMID- 14635841
TI  - Mitochondrial differentiation in a polymorphic land snail: evidence for
      Pleistocene survival within the boundaries of permafrost.
AB  - The genetic differentiation of populations having colonized formerly unsuitable
      habitats after the Pleistocene glaciations depends to a great extent on the speed
      of expansion. Slow dispersers maintain their refugial diversity whereas fast
      dispersal leads to a reduction of diversity in the newly colonized areas. During
      the Pleistocene, almost the entire current range of the land snail Arianta
      arbustorum has repeatedly been covered with ice or been subjected to permafrost.
      Owing to the low potential for dispersal of land snails, slow (re)colonization of
      the wide range from southern refugia can be excluded. Alternatively, fast,
      passive dispersal from southern refugia or survival in and expansion from
      multiple refugia within the area subjected to permafrost may account for the
      current distribution. To distinguish between these scenarios we reconstructed a
      phylogeography based on the sequences of a fragment of the cytochrome oxidase I
      from 133 individuals collected at 45 localities and analysed the molecular
      variance. Seventy-five haplotypes were found that diverged on average at 7.52% of
      positions. This high degree of diversity suggests that A. arbustorum is an old
      species in which the population structure, isolation and the hermaphroditic
      nature have reduced the probability of lineage extinction. The genetic structure
      was highly significant with the highest variance partition found among regions.
      Geographic distance and mitochondrial differentiation were not congruent.
      Lineages had overlapping ranges. The clear genetic differentiation and the patchy
      pattern of haplotype distribution suggest that colonization of formerly
      unsuitable habitats was mainly achieved from multiple populations from within the
      permafrost area.

PMID- 14635842
TI  - A role for the mismatch repair system during incipient speciation in
      Saccharomyces.
AB  - The cause of reproductive isolation between biological species is a major issue
      in the field of biology. Most explanations of hybrid sterility require either
      genetic incompatibilities between nascent species or gross physical imbalances
      between their chromosomes, such as rearrangements or ploidy changes. An
      alternative possibility is that genomes become incompatible at a molecular level,
      dependent on interactions between primary DNA sequences. The mismatch repair
      system has previously been shown to contribute to sterility in a hybrid between
      established yeast species by preventing successful meiotic crossing-over leading
      to aneuploidy. This system could also promote or reinforce the formation of new
      species in a similar manner, by making diverging genomes incompatible in meiosis.
      To test this possibility we crossed yeast strains of the same species but from
      diverse historical or geographic sources. We show that these crosses are
      partially sterile and present evidence that the mismatch repair system is largely
      responsible for this sterility.

PMID- 14635843
TI  - A linear dominance hierarchy among clones in chimeras of the social amoeba
      Dictyostelium discoideum.
AB  - Amoebae from different clones of Dictyostelium discoideum aggregate into a common
      slug, which migrates towards light for dispersal, then forms a fruiting body
      consisting of a somatic, dead stalk, holding up a head of living spores.
      Contributions of two clones in a chimera to spore and stalk are often unequal,
      with one clone taking advantage of the other's stalk contribution. To determine
      whether there was a hierarchy of exploitation among clones, we competed all
      possible pairs among seven clones and measured their relative representation in
      the prespore and prestalk stages and in the final spore stage. We found a clear
      linear hierarchy at the final spore stage, but not at earlier stages. These
      results suggest that there is either a single principal mechanism or additive
      effects for differential contribution to the spore, and that it involves more
      than spore/stalk competition.

PMID- 14635844
TI  - Male parentage does not vary with colony kin structure in a multiple-queen ant.
AB  - Kin selection theory predicts that, in social Hymenoptera, the parentage of males
      should be determined by within-colony relatedness. We present a model showing
      that, when sex ratios are split (bimodal) as a function of colony kin structure,
      the predictions of kin selection theory regarding the occurrence of worker
      reproduction and policing (prevention of worker reproduction) require
      modification. To test the predictions of kin selection theory and our model, we
      estimated using microsatellites the frequency of worker-produced male eggs and
      adults in the facultatively polygynous (multiple-queen) ant Leptothorax
      acervorum. Analysis of 210 male eggs and 328 adult males from 13 monogynous
      (single-queen) and nine polygynous colonies demonstrated that the frequency of
      worker-produced males was low (2.3-4.6% of all males) and did not differ
      significantly between colony classes or between eggs and adults. This suggested
      workers' self-restraint as the cause of infrequent worker reproduction in both
      colony classes. Such an outcome is not predicted either by comparing relatedness
      values or by our model. Therefore, it appears that factors other than colony kin
      structure and sex ratio effects determine the pattern of male parentage in the
      study population. A likely factor is a colony-level cost of worker reproduction.

PMID- 14635845
TI  - Evolution of RNA virus in spatially structured heterogeneous environments.
AB  - A hallmark of the infectious cycle for many RNA viruses parasitizing
      multicellular hosts is the need to invade and successfully replicate in tissues
      that comprise a variety of cell types. Thus, multicellular hosts represent a
      heterogeneous environment to evolving viral populations. To understand viral
      adaptation to multicellular hosts, we took a double approach. First, we developed
      a mathematical model that served to make predictions concerning the dynamics of
      viral populations evolving in heterogeneous environments. Second, the predictions
      were tested by evolving vesicular stomatitis virus in vitro on a spatially
      structured environment formed by three different cell types. In the absence of
      gene flow, adaptation was tissue-specific, but fitness in all tissues decreased
      with migration rate. The performance in a given tissue was negatively correlated
      with its distance to the tissue hosting the population. This correlation
      decreased with migration rate.

PMID- 14635846
TI  - Two species of feminizing microsporidian parasite coexist in populations of
      Gammarus duebeni.
AB  - The amphipod crustacean Gammarus duebeni hosts two species of vertically
      transmitted microsporidian parasites, Nosema granulosis and Microsporidium sp. A.
      Here it is demonstrated that these co-occurring parasite species both cause
      infected females to produce female-biased broods. A survey of European G. duebeni
      populations demonstrates that these two parasites co-occur in six of 10
      populations. These findings contrast with the theoretical prediction that two
      vertically transmitted feminizing parasites should not coexist in a panmictic
      population of susceptible hosts at equilibrium. Possible explanations for the co
      occurrence of the two feminizing microsporidia in G. duebeni include the recent
      invasion of a new parasite, horizontal transmission of one or both parasites and
      the spread of alleles for resistance to the dominant parasite in host
      populations.

PMID- 14635847
TI  - Effects of four generations of density-dependent selection on life history traits
      and their plasticity in a clonally propagated plant.
AB  - Life history evolution of many clonal plants takes place with long periods of
      exclusively clonal reproduction and under largely varying ramet densities
      resulting from clonal reproduction. We asked whether life history traits of the
      clonal herb Ranunculus reptans respond to density-dependent selection, and
      whether plasticity in these traits is adaptive. After four generations of
      exclusively clonal propagation of 16 low and 16 high ramet-density lines, we
      studied life history traits and their plasticities at two test ramet-densities.
      Plastic responses to higher test-density consisted of a shift from sexual to
      vegetative reproduction, and reduced flower production, plant size, branching
      frequency, and lengths of leaves and internodes. Plants of high-density lines
      tended to have longer leaves, and under high test-density branched less
      frequently than those of low-density lines. Directions of these selection
      responses indicate that the observed plastic branching response is adaptive,
      whereas the plastic leaf length response is not. The reverse branching frequency
      pattern at low test-density, where plants of high-density lines branched more
      frequently than those of low-density lines, indicates evolution of plasticity in
      branching. Moreover, when grown under less stressful low test-density, plants of
      high-density lines tended to grow larger than the ones of low-density lines. We
      conclude that ramet density affects clonal life-history evolution and that under
      exclusively clonal propagation clonal life-history traits and their plasticities
      evolve differently at different ramet densities.

PMID- 14635848
TI  - Sexual conflict in Sepsis cynipsea: female reluctance, fertility and mate choice.
AB  - Sexual conflict can elevate mating costs via male inflicted damage to females.
      Possible selective advantages to males include decreasing the likelihood that
      females remate and/or increasing females' current reproductive investment in a
      manner analogous to terminal reproductive investment. We investigated female
      mating behaviour relative to their number of previous copulations in the fly
      Sepsis cynipsea, and whether males accepted as first mates were more likely to be
      accepted again. Females were more likely to remate with new rather than original
      males, although there was no associated fitness benefit, and in contrast to
      theoretical predictions, females became less reluctant to remate as the number of
      previous copulations increased. Additionally, females did not increase
      reproductive investment as would be expected if they were ensuring their final
      reproductive efforts were maximized by remating. This suggests that damaging
      females is a pleiotropic effect which inadvertently leads to increased, not
      decreased, polyandry.

PMID- 14635849
TI  - Sexual selection, antennae length and the mating advantage of large males in
      Asellus aquaticus.
AB  - In crustacean species with precopulatory mate-guarding, sexual size dimorphism
      has most often been regarded as the consequence of a large male advantage in
      contest competition for access to females. However, large body size in males may
      also be favoured indirectly through scramble competition. This might partly be
      the case if the actual target of selection is a morphological character, closely
      correlated with body size, involved in the detection of receptive females. We
      studied sexual selection on body size and antennae length in natural populations
      of Asellus aquaticus, an isopod species with precopulatory mate guarding. In this
      species, males are larger than females and male pairing success is positively
      related to body size. However, males also have longer antennae, relative to body
      size, than females, suggesting that this character may also be favoured by sexual
      selection. We used multivariate analysis of selection to assess the relative
      influences of body size and antennae length in five different populations in the
      field. Selection gradients indicated that, overall, body size was a better
      predictor of male pairing success than antennae length, although some variation
      was observed between sites. We then manipulated male antennae length in a series
      of experiments conducted in the lab, and compared the pairing ability of males
      with short or long antennae. Males with short antennae were less likely to
      detect, orient to, and to pair with a receptive female compared with males with
      long antennae. We discuss the implications of our results for studies of male
      body size and sexual dimorphism in relation to sexual selection in crustaceans.

PMID- 14635850
TI  - Environment-dependent reversal of a life history trade-off in the seed beetle
      Callosobruchus maculatus.
AB  - Environmental manipulations have consistently demonstrated a cost of reproduction
      in the capital-breeding seed beetle, Callosobruchus maculatus, as females
      deprived of seeds or mates lay fewer eggs and thereby increase their longevity.
      Yet fecundity and longevity tend to be positively correlated within populations,
      perhaps as a consequence of individual differences in resource acquisition. We
      conducted a split-brood experiment that combined a manipulation of seed
      availability (seeds present or absent) with a quantitative-genetic analysis of
      fecundity and lifespan in each environment. Each trait was significantly
      heritable in each environment. Seed availability not only altered mean fecundity
      and longevity between environments, but also modified how the traits were
      correlated within environments. The signs of both the phenotypic and genetic
      correlations switched from positive when seeds were present to negative when
      seeds were absent. This reversal persisted even after the effect of body mass (a
      potential indicator of resource acquisition) was statistically controlled. Cross
      environment genetic correlations were positive but significantly less than one
      for each trait. We suggest that the reversal of the fecundity-longevity
      relationship depends on a shift in the relative importance of resource
      acquisition and resource-allocation loci between environments. In particular, a
      cost of reproduction may be apparent at the individual level only when seeds are
      scarce or absent because differences in reproductive effort become large enough
      to overwhelm differences in resource acquisition. Despite their common dependence
      on resources acquired during larval stages, fecundity and lifespan in C.
      maculatus do not appear to be tightly coupled in a physiological or genetic
      sense.

PMID- 14635851
TI  - Adaptive seasonal trend in brood sex ratio: test in two sister species with
      contrasting breeding systems.
AB  - Evolutionary theory predicts adaptive adjustment in offspring sex ratio by
      females. Seasonal change in sex ratio is one possibility, tested here in two
      sister species, the Common sandpiper and the Spotted sandpiper Actitis hypoleucos
      and A. macularia. In the monogamous Common sandpiper, males are the most
      competitive sex. In each of 3 years, there was a change from mainly sons in early
      clutches to mainly daughters in late clutches. This seasonal adjustment of clutch
      sex ratio took place within the female before the eggs were laid, not by
      differential egg or chick survival. The sex of all eggs laid in the clutches used
      here was determined molecularly from chick blood taken at the time of hatching.
      The Spotted sandpiper in contrast is polyandrous, with partly reversed sex roles.
      There was no seasonal trend from sons to daughters in this species. When tested
      together, the two species differed significantly as predicted by the hypothesis
      of adaptive sex ratio adjustment by females.

PMID- 14635852
TI  - Maternal antibodies but not carotenoids in barn swallow eggs covary with embryo
      sex.
AB  - Mothers influence their offspring phenotype by varying egg quality. Such maternal
      effects may be mediated by transmission of antibodies and antioxidants. Mothers
      should adjust allocation of maternal substances depending on embryonic sex
      because of differences in reproductive value, potentially dependent on paternal
      genetic effects as reflected by secondary sexual characters. We manipulated
      sexual attractiveness of male barn swallows (Hirundo rustica) and investigated
      maternal investment in eggs in relation to offspring sex. Mothers allocated more
      antibodies against a pathogen to eggs with a daughter than a son. However,
      concentration of antioxidants was independent of embryonic sex. Sex-dependent
      allocation was independent of paternal attractiveness. Thus, mothers adjusted
      allocation of substances to offspring in a complex manner, that may be part of a
      strategy of favouritism of daughters, which have larger mortality than sons. Such
      effects may have important consequences for secondary and tertiary sex ratios,
      but also for ontogeny of adult phenotype.

PMID- 14635853
TI  - Females avoid manipulative males and live longer.
AB  - Female mate choice has been demonstrated in a wide variety of species and is now
      accepted as an important factor in sexual selection. One of the remaining
      questions, however, is why females prefer specific males. Do females or their
      offspring benefit from their choice? Or do females choose mates to minimize costs
      of mating? Here we show that, in the ovoviviparous cockroach Nauphoeta cinerea,
      where sexual selection has been well documented, females chose mates to avoid
      costly male manipulation. Females were partnered with preferred or nonpreferred
      mates, and fitness of the females measured. We found that females lived longer
      when they mated with preferred males. Female lifespan depended on the rate at
      which offspring developed from egg to parturition: slower development led to
      longer life. We manipulated the male pheromone and showed that the component of
      the pheromone blend that makes males attractive to females also delayed
      parturition. Thus, like other aspects of sexual conflict in this species,
      offspring development and thereby the mother's lifespan depended on exposure of
      females to specific components of the male pheromone. Males benefit from
      manipulating offspring development because females with accelerated parturition
      remained unreceptive whereas females with slower developing offspring readily
      remated after giving birth to their offspring. Our results suggest a hormone-like
      role for the male pheromone in N. cinerea and provide the first direct evidence
      of mate choice to avoid male manipulation. This study shows that dominant males
      may not be preferred males if they are manipulating females, why multiple
      components with contrasting effects can exist in a sexual signal, and emphasizes
      the complex fitness relationships that can arise in species with sexual conflict.

PMID- 14635854
TI  - The emergence of cetaceans: phylogenetic analysis of male social behaviour
      supports the Cetartiodactyla clade.
AB  - The phylogeny of cetaceans is still unresolved. Two hypotheses prevail for the
      position of cetaceans among ungulates. The first hypothesis shows that
      Artiodactyla is monophyletic and is sister taxon to a clade composed of cetaceans
      and mesonychians. The second one shows that Artiodactyla is paraphyletic and
      contains Cetacea that is sister taxon of Hippopotamida. These hypotheses are
      based on fossil records and molecular studies. The behaviour of extant species
      can provide as much phylogenetic information as other classical parameters. I
      considered the behaviour observed during male agonistic interactions in placental
      mammals in order to determine which of these hypotheses was supported by the
      behaviour of extant species. Headbutting was only observed in ruminants,
      hippopotamids and cetaceans, supporting the paraphyletic nature of Artiodactyla.
      Primitive ruminants (tragulids) and two genera of ruminants (Moschus and
      Oreamnos) were not observed headbutting. These secondary losses were only present
      in 6.25% of the 48 surveyed ruminant genera. Head-to-head attacks emerged in
      pigs, which have developed dermal protusions. Yet, these confrontations are not
      based on mutual blow delivery. The behavioural evidence supports the inclusion of
      cetaceans in Artiodactyla.

PMID- 14635855
TI  - Reproductive isolation and hybrid pollen disadvantage in Ipomopsis.
AB  - One cause of reproductive isolation is gamete competition, in which conspecific
      pollen has an advantage over heterospecific pollen in siring seeds, thereby
      decreasing the formation of F1 hybrids. Analogous pollen interactions between
      hybrid pollen and conspecific pollen can contribute to post-zygotic isolation.
      The herbaceous plants Ipomopsis aggregata and I. tenuituba frequently hybridize
      in nature. Hand-pollination of I. aggregata with pollen from F1 or F2 hybrids
      produced as many seeds as hand-pollination with conspecific pollen, suggesting
      equal pollen viability. However, when mixed pollen loads with 50% conspecific
      pollen and 50% hybrid pollen were applied to I. aggregata stigmas, fewer than
      half of the seeds had hybrid sires. Such pollen mixtures are frequently received
      if plants of the two species and F1 and F2 hybrids are intermixed, suggesting
      that this advantage of conspecific over hybrid pollen reduces backcrossing and
      contributes to reproductive isolation.

PMID- 14635856
TI  - Species concepts and species reality: salvaging a Linnaean rank.
AB  - The validity of the species category (rank) as a distinct level of biological
      organization has been questioned. Phenetic, cohesion and monophyletic species
      concepts do not delimit species-level taxa that are qualitatively distinct from
      lower or higher taxa: all organisms throughout the tree of life exhibit varying
      degrees of similarity, cohesion, and monophyly. In contrast, interbreeding
      concepts delimit species-level taxa characterized by a phenomenon (regular gene
      flow) not found in higher taxa, making the species category a distinct level of
      biological organization. Only interbreeding concepts delimit species-level taxa
      that are all comparable according to a biologically meaningful criterion and
      qualitatively distinct from entities assigned to other taxonomic categories.
      Consistent application of interbreeding concepts can result in counterintuitive
      taxonomies--e.g. many wide polytypic species in plants and narrow cryptic species
      in animals. However, far from being problematic, such differences are
      biologically illuminating--reflecting differing barriers to gene flow in
      different clades. Empirical problems with interbreeding concepts exist, but many
      of these also apply to other species concepts, whereas others are not as severe
      as some have argued. A monistic view of species using interbreeding concepts will
      encounter strong historical inertia, but can save the species category from
      redundancy with other categories, and thus justify continued recognition of the
      species category.

PMID- 14635857
TI  - Genetic variation in organisms with sexual and asexual reproduction.
AB  - The genetic variation in a partially asexual organism is investigated by two
      models suited for different time scales. Only selectively neutral variation is
      considered. Model 1 shows, by the use of a coalescence argument, that three
      sexually derived individuals per generation are sufficient to give a population
      the same pattern of allelic variation as found in fully sexually reproducing
      organisms. With less than one sexual event every third generation, the
      characteristic pattern expected for asexual organisms appear, with strong allelic
      divergence between the gene copies in individuals. At intermediary levels of
      sexuality, a complex situation reigns. The pair-wise allelic divergence under
      partial sexuality exceeds, however, always the corresponding value under full
      sexuality. These results apply to large populations with stable reproductive
      systems. In a more general framework, Model 2 shows that a small number of sexual
      individuals per generation is sufficient to make an apparently asexual population
      highly genotypically variable. The time scale in terms of generations needed to
      produce this effect is given by the population size and the inverse of the rate
      of sexuality.

PMID- 14635858
TI  - Testing the link between the latitudinal gradient in species richness and rates
      of molecular evolution.
AB  - Numerous hypotheses have been proposed to explain latitudinal gradients in
      species richness, but all are subject to ongoing debate. Here we examine Rohde's
      (1978, 1992) hypothesis, which proposes that climatic conditions at low latitudes
      lead to elevated rates of speciation. This hypothesis predicts that rates of
      molecular evolution should increase towards lower latitudes, but this prediction
      has never been tested. We discuss potential links between rates of molecular
      evolution and latitudinal diversity gradients, and present the first test of
      latitudinal variation in rates of molecular evolution. Using 45 phylogenetically
      independent, latitudinally separated pairs of bird species and higher taxa, we
      compare rates of evolution of two mitochondrial genes and DNA-DNA hybridization
      distances. We find no support for an effect of latitude on rate of molecular
      evolution. This result casts doubt on the generality of a key component of
      Rohde's hypothesis linking climate and speciation.

PMID- 14635859
TI  - Host choice promotes reproductive isolation between host races of the larch
      budmoth Zeiraphera diniana.
AB  - The chances for sympatric speciation are improved if ecological divergence leads
      to assortative mating as a by-product. This effect is known in parasites that
      find mates using host cues, but studies of larch- and pine-feeding races of the
      larch budmoth (Zeiraphera diniana, Lepidoptera: Tortricidae) suggest it may also
      occur when mate attraction is via sex pheromones that are independent of habitat.
      We have previously shown that females releasing pheromones on or near their own
      host attract more males of their own race than if placed on the alternative host.
      This host effect would enhance assortative mating provided adults preferentially
      alight on their native hosts. Here we investigate alighting preferences in
      natural mixed forest using a novel likelihood analysis of genotypic clusters
      based on three semidiagnostic allozyme loci. Both larch and pine females show a
      realized alighting preference for their own host of 86%. The equivalent
      preferences of males were 79% for the larch race and 85% for the pine race. These
      preferences are also detectable in small-scale laboratory experiments, where
      alighting preferences of larch and pine races towards their own hosts were,
      respectively, 67 and 66% in females and 69 and 63% in males. Pure larch race
      moths reared in the laboratory had alighting choice similar to moths from natural
      populations, while hybrids were intermediate, showing that alighting preferences
      were heritable and approximately additive. The field estimates of alighting
      preference, coupled with earlier work on mate choice, yield an estimated rate of
      natural hybridization between sympatric host races of 2.2-3.8% per generation.
      Divergent alighting choice enhances pheromone-mediated assortative mating today,
      and is likely to have been an important cause of assortative mating during
      initial divergence in host use. Because resources are normally 'coarse-grained'
      in space and time, assortative mating due to ecological divergence may be a more
      important catalyst of sympatric speciation than generally realized.

PMID- 14635860
TI  - The origin of interlocus sexual conflict: is sex-linkage important?
AB  - Sexual conflict has been proposed as a potential selective agent in the evolution
      of a variety of traits. Here, we present a simple model that investigates the
      initial conditions under which sex-linked and sex-limited harming alleles can
      invade a population. In this paper, we expand previous threshold models to study
      how sex-linkage and sex determination mechanisms affect the spreading conditions
      of a harming allele. Our models provide new insights into how sexual conflict
      could originate, showing that in diploid organisms the probability of a new
      harming allele spreading is independent of both the genetic sex determination
      system and the dominance relationships. However, the incidence of interlocus
      sexual conflicts in the initial steps of the invasion critically depends on the
      inheritance system.

PMID- 14635861
TI  - Multiple parasites are driving major histocompatibility complex polymorphism in
      the wild.
AB  - Parasite mediated selection may result in arms races between host defence and
      parasite virulence. In particular, simultaneous infections from multiple parasite
      species should cause diversification (i.e. balancing selection) in resistance
      genes both at the population and the individual level. Here, we tested these
      ideas in highly polymorphic major histocompatibility complex (MHC) genes from
      three-spined sticklebacks (Gasterosteus aculeatus L.). In eight natural
      populations, parasite diversity (15 different species), and MHC class IIB
      diversity varied strongly between habitat types (lakes vs. rivers vs. estuaries)
      with lowest values in rivers. Partial correlation analysis revealed an influence
      of parasite diversity on MHC class IIB variation whereas general genetic
      diversity assessed at seven microsatellite loci was not significantly correlated
      with parasite diversity. Within individual fish, intermediate, rather than
      maximal allele numbers were associated with minimal parasite load, supporting
      theoretical models of self-reactive T-cell elimination. The optimal individual
      diversity matched those values female fish try to achieve in their offspring by
      mate choice. We thus present correlative evidence supporting the 'allele
      counting' strategy for optimizing the immunocompetence in stickleback offspring.

PMID- 14635862
TI  - Suboptimal timing of reproduction in Lobelia inflata may be a conservative bet
      hedging strategy.
AB  - Age and size at reproduction are important components of fitness, and are
      variable both within and among angiosperm species. The fitness consequences of
      such life-history variation are most readily studied in organisms that reproduce
      only once in their lifetime. The timing of the onset of reproduction (bolting) in
      the monocarpic perennial, Lobelia inflata, occurs over a range of dates within a
      season, and may be postponed to a later year. Empirical relationships among life
      history traits, derived from over 950 wild-growing and experimentally manipulated
      plants in the field, are used to model an optimal changing size threshold (norm
      of reaction) for bolting over the growing season. Comparisons are made between
      observed and expected norms of reaction governing bolting. An apparently
      suboptimal bolting schedule that precludes bolting beyond an early (conservative)
      date is observed, and is found to be qualitatively consistent with conservative
      bet hedging under unpredictable season lengths. On this basis we propose the
      schedule of bolting as a plausible example of a conservative bet-hedging
      strategy. The results underscore the critical need for long-term studies of
      fluctuating selection to distinguish suboptimality from bet hedging.

PMID- 14635863
TI  - Maternal control of offspring sex and male morphology in the Otitesella fig
      wasps.
AB  - Models concerning the evolution of alternative mating tactics commonly assume
      that individuals determine their own strategies. Here we develop a computer-based
      ESS model that allows mothers, ovipositing in discrete patches, to choose both
      the sex and the male mating tactics (natal-patch mating or dispersing) of their
      offspring based only on how many other mothers have used the specific patch
      before them. Data for three species of nonpollinating fig wasps from the
      Otitesella genus agree quantitatively with the model's assumptions and
      predictions. This suggests that females respond to population densities at the
      level of individual figs. The alternative male tactics in the species we studied
      are probably a result of a conditional strategy exercised by the mother that laid
      them. In addition, as females were only allowed to lay one egg per patch, our
      results suggest a new mechanism that can skew population sex ratios towards a
      female bias.

PMID- 14635864
TI  - Worker interests and male production in Polistes gallicus, a Mediterranean social
      wasp.
AB  - The resolution of social conflict in colonies may accord with the interests of
      the most numerous party. In social insect colonies with single once-mated queens,
      workers are more closely related to the workers' sons than they are to the
      queens' sons. Therefore, they should prefer workers to produce males, against the
      queen's interests. Workers are capable of producing males as they arise from
      unfertilized eggs. We found Polistes gallicus to have colonies of single, once
      mated queens, as determined by microsatellite genotyping of the workers, so
      worker interests predict worker male production. In colonies lacking queens,
      workers produced the males, but not in colonies with original queens. Thus worker
      interests were expressed only when the queen was gone. The high fraction of
      missing queens and early end to the colony cycle relative to climate so early in
      the season is surprising and may indicate a forceful elimination of the queen.

PMID- 14635865
TI  - Spatially structured genetic variation in a broadcast spawning bivalve:
      quantitative vs. molecular traits.
AB  - Understanding the origin, maintenance and significance of phenotypic variation is
      one of the central issues in evolutionary biology. An ongoing discussion focuses
      on the relative roles of isolation and selection as being at the heart of
      genetically based spatial variation. We address this issue in a representative of
      a taxon group in which isolation is unlikely: a marine broadcast spawning
      invertebrate. During the free-swimming larval phase, dispersal is potentially
      very large. For such taxa, small-scale population genetic structuring in neutral
      molecular markers tends to be limited, conform expectations. Small-scale
      differentiation of selective traits is expected to be hindered by the putatively
      high gene flow. We determined the geographical distribution of molecular markers
      and of variation in a shell shape measure, globosity, for the bivalve Macoma
      balthica (L.) in the western Dutch Wadden Sea and adjacent North Sea in three
      subsequent years, and found that shells of this clam are more globose in the
      Wadden Sea. By rearing clams in a common garden in the laboratory starting from
      the gamete phase, we show that the ecotypes are genetically different;
      heritability is estimated at 23%. The proportion of total genetic variation that
      is between sites is much larger for the morphological additive genetic variation
      (QST = 0.416) than for allozyme (FST = 0.000-0.022) and mitochondrial DNA
      cytochrome-c-oxidase-1 sequence variation (phiST = 0.017). Divergent selection
      must be involved and intraspecific spatial genetic differentiation in marine
      broadcast spawners is apparently not constrained by low levels of isolation.

PMID- 14635866
TI  - Inbreeding depression and genetic load of sexually selected traits: how the guppy
      lost its spots.
AB  - To date, few studies have investigated the effects of inbreeding on sexually
      selected traits, although inbreeding depression on such traits can play an
      important role in the evolution and ecology of wild populations. Sexually
      selected traits such as ornamentation and courtship behaviour may not be primary
      fitness characters, but selection and dominance coefficients of their mutations
      will resemble those of traits under natural selection. Strong directional
      selection, for instance, through female mate-choice, purges all but the most
      recessive deleterious mutations, and the remaining dominance variation will
      result in inbreeding depression once populations undergo bottlenecks. We analysed
      the effects of inbreeding on sexually selected traits (colour pattern and
      courtship behaviour) in the male guppy, Poecilia reticulata, from Trinidad, and
      found a significant decline in the frequency of mating behaviour and colour
      spots. Such effects occurred although the genetic basis of these traits, many of
      which are Y-linked and hemizygous, would be expected to leave relatively little
      scope for inbreeding depression. Findings suggest that these sexually selected
      traits could reflect the genetic condition or health of males, and thus may be
      informative mate-cue characters for female choice as suggested by the 'good
      genes' model.

PMID- 14635867
TI  - Geographic range size, life history and rates of diversification in Australian
      mammals.
AB  - What causes species richness to vary among different groups of organisms? Two
      hypotheses are that large geographical ranges and fast life history either reduce
      extinction rates or raise speciation rates, elevating a clade's rate of
      diversification. Here we present a comparative analysis of these hypotheses using
      data on the phylogenetic relationships, geographical ranges and life history of
      the terrestrial mammal fauna of Australia. By comparing species richness patterns
      to null models, we show that species are distributed nonrandomly among genera.
      Using sister-clade comparisons to control for clade age, we then find that faster
      diversification is significantly associated with larger geographical ranges and
      larger litters, but there is no evidence for an effect of body size or age at
      first breeding on diversification rates. We believe the most likely explanation
      for these patterns is that larger litters and geographical ranges increase
      diversification rates because they buffer species from extinction. We also
      discuss the possibility that positive effects of litter size and range size on
      diversification rates result from elevated speciation rates.

PMID- 14635868
TI  - Frequency dependence in matings with water-borne sperm.
AB  - Negative frequency-dependent mating success--the rare male effect--is a
      potentially powerful evolutionary force, but disagreement exists as to whether
      previous work, focusing on copulating species, has robustly demonstrated this
      phenomenon. Noncopulating sessile organisms that release male gametes into the
      environment but retain their eggs for fertilization may routinely receive unequal
      mixtures of sperm. Although promiscuity seems unavoidable it does not follow that
      the resulting paternity obeys 'fair raffle' expectations. This study investigates
      frequency dependence in the mating of one such species, the colonial ascidian
      Diplosoma listerianum. In competition with an alternative sperm source males
      fathered more progeny if previously mated to a particular female than if no
      mating history existed. This suggests positive frequency-dependent selection, but
      may simply result from a mate order effect involving sperm storage. With fewer
      acclimation matings, separated by longer intervals, this pattern was not found.
      When, in a different experimental design, virgin females were given simultaneous
      mixtures of gametes at widely divergent concentrations, sperm at the lower
      frequency consistently achieved a greater than expected share of paternity--a
      rare male effect. A convincing argument as to why D. listerianum should favour
      rare sperm has not been identified, as sperm rarity is expected to correlate very
      poorly with ecological or genetic male characteristics in this pattern of mating.
      The existence of nongenetic female preferences at the level of colony modules,
      analogous in effect to fixed female preferences, is proposed. If visible to
      selection, indirect benefits from increasing the genetic diversity of a sibship
      appear the only likely explanation of the rare male effect in this system as the
      life history presents virtually no costs to multiple mating, and a near absence
      of direct (resource) benefits, whereas less controversial hypotheses of female
      promiscuity (e.g. trade up, genetic incompatibility) do not seem appropriate.

PMID- 14635869
TI  - A direct experimental test of founder-flush effects on the evolutionary potential
      for assortative mating.
AB  - Founder-flush speciation models propose that population bottlenecks can enhance
      evolutionary potential for reproductive isolation. To test this prediction, we
      subjected bottlenecked (three-pair founder-flush) and nonbottlenecked populations
      of the housefly to 18 generations of selection for assortative mating. After the
      selection regime, we analysed videotaped courtship bouts in these lines to
      identify correlated responses to the selection protocol. The realized
      heritabilities for assortative mating for both the bottlenecked and
      nonbottlenecked treatments were very low, but still significant. The founder
      flush populations had thus responded to selection as well as the nonbottlenecked
      populations, although not significantly greater (i.e. total increases in
      assortative mating were 9.6 and 8.6%, respectively). Multivariate analyses on the
      courtship repertoires found that, although both bottlenecked and nonbottlenecked
      treatments attained similar levels of assortative mating, the treatments
      exhibited different evolutionary solutions in their correlated responses.
      Specifically, the bottlenecked lines demonstrated a significantly more diverse
      set of evolutionary trajectories (i.e. significant shifts along the second
      principal component for courtship). This suggests that the bottlenecked lines had
      greater potential for the evolution of novel phenotypes as predicted by founder
      induced speciation models. Our results, however, cannot distinguish whether the
      more variable evolutionary responses resulted from increased heritabilities in
      courtship components, reduced potential to follow the convergent evolutionary
      trajectories noted for the nonbottlenecked lines, or some combination of both
      general processes in determining the resultant multivariate phenotype.

PMID- 14635870
TI  - Evolution in stressful environments II: adaptive value and costs of plasticity in
      response to low light in Sinapis arvensis.
AB  - Plants possess a remarkable capacity to alter their phenotype in response to the
      highly heterogeneous light conditions they commonly encounter in natural
      environments. In the present study with the weedy annual plant Sinapis arvensis,
      we (a) tested for the adaptive value of phenotypic plasticity in morphological
      and life history traits in response to low light and (b) explored possible
      fitness costs of plasticity. Replicates of 31 half-sib families were grown
      individually in the greenhouse under full light and under low light (40% of
      ambient) imposed by neutral shade cloth. Low light resulted in a large increase
      in hypocotyl length and specific leaf area (SLA), a reduction in juvenile biomass
      and a delayed onset of flowering. Phenotypic selection analysis within each light
      environment revealed that selection favoured large SLA under low light, but not
      under high light, suggesting that the observed increase in SLA was adaptive. In
      contrast, plasticity in the other traits measured was maladaptive (i.e. in the
      opposite direction to that favoured by selection in the low light environment).
      We detected significant additive genetic variance in plasticity in most
      phenotypic traits and in fitness (number of seeds). Using genotypic selection
      gradient analysis, we found that families with high plasticity in SLA had a lower
      fitness than families with low plasticity, when the effect of SLA on fitness was
      statistically kept constant. This indicates that plasticity in SLA incurred a
      direct fitness cost. However, a cost of plasticity was only expressed under low
      light, but not under high light. Thus, models on the evolution of phenotypic
      plasticity will need to incorporate plasticity costs that vary in magnitude
      depending on environmental conditions.

PMID- 14635871
TI  - Functional trade-offs in the limb muscles of dogs selected for running vs.
      fighting.
AB  - The physical demands of rapid and economical running differ from those of
      physical fighting such that functional trade-offs may prevent simultaneous
      evolution of optimal performance in both behaviours. Here we test three
      hypotheses of functional trade-off by measuring determinants of limb
      musculoskeletal function in two breeds of domestic dogs that have undergone
      intense artificial selection for running (Greyhound) or fighting performance (Pit
      Bull). We found that Greyhounds differ from Pit Bulls in having relatively less
      muscle mass distally in their limbs, weaker muscles in their forelimbs than their
      hindlimbs, and a much greater capacity for elastic storage in the in-series
      tendons of the extensor muscles of their ankle joints. These observations are
      consistent with the hypothesis that specialization for rapid or economical
      running can limit fighting performance and vice versa. We suggest that functional
      trade-offs that prevent simultaneous evolution of optimal performance in both
      locomotor and fighting abilities are widespread taxonomically.

PMID- 14635872
TI  - Spatial and demographic population genetic structure in Catasetum viridiflavum
      across a human-disturbed habitat.
AB  - Spatial and temporal genetic structures were examined across sites on islands and
      mainland (continuous forest) populations of an epiphytic orchid, Catasetum
      viridiflavum, using 17 polymorphic allozyme loci. I tested whether patches on
      islands or at mainland sites comprised small local populations or a large
      population. Low among population differentiation was observed across the
      landscape suggesting that the species-specific pollinator and tiny wind-dispersed
      seeds maintain interconnections among distant patches. Temporal genetic structure
      among stage classes, and among breeding individuals are important components of
      the maintenance of genetic variation in this orchid. The natural history of this
      species including small breeding populations, probable high frequency of mating
      among relatives, and the high rates of seed movement among sites contribute to
      the high FIS. These data show that physically isolated patches in this epiphytic
      orchid comprise a single larger genetic population, which is independent of the
      physical distances among sites. Although quite different in ecological and life
      history characteristics, the genetic structure of this orchid demonstrates a
      pattern similar to temperate and tropical trees in fragmented landscapes.

PMID- 14635873
TI  - Spatial ecological and genetic structure of a mixed population of sexual diploid
      and apomictic triploid dandelions.
AB  - Ecological differentiation is widely seen as an important factor enabling the
      stable coexistence of closely related plants of different ploidy levels. We
      studied ecological and genetic differentiation between co-occurring sexual
      diploid and apomictic triploid Taraxacum section Ruderalia by analysing spatial
      patterns both in the distribution of cytotypes and in the distribution of genetic
      variation within and between the cytotypes. A significant relationship between
      ploidy level and elevation was found. This mode of ecological differentiation
      however, was not sufficient to explain the significant spatial structure in the
      distribution of diploids and triploids within the population. Strong congruence
      was found between the spatial genetic patterns within the diploids and within the
      triploids. We argue that this congruence is an indication of gene flow between
      neighbouring plants of different ploidy levels.

PMID- 14635874
TI  - Differential strength of sex-biased hybrid inferiority in impeding gene flow may
      be a cause of Haldane's rule.
AB  - In animals, if one sex of the F1 hybrid between two species is sterile or
      inviable, it is usually the heterogametic (XY or WZ) sex. This phenomenon, known
      as Haldane's rule, is currently thought to be coincidentally caused by different
      mechanisms in separate entities. The following questions have never been asked:
      Are heterogametic and homogametic inferiority (sterility or inviability)
      equivalent as isolating mechanisms? Could discrepancies between them, if
      existing, produce Haldane's rule? Here I consider sex-biased hybrid inferiority
      strictly as an isolating mechanism, and quantitatively evaluate its strength in
      impeding gene flow. The comparison reveals that the ability of sex-biased
      inferiority to impede gene flow varies according to the sex and chromosome
      involved. Heterogametic inferiority is a weaker barrier when unidirectional and a
      much stronger one when in compound reciprocal directions, compared with
      homogametic inferiority. Such differential strength may affect divergence in
      speciation and produce Haldane's rule.

PMID- 14635875
TI  - Female choice of sexually antagonistic male adaptations: a critical review of
      some current research.
AB  - We contrast some recent uses of the concept of male-female conflict, with the
      type of conflict that is inherent in traditional Darwinian female choice. Females
      in apparent conflict situations with males may suffer reduced lifetime
      reproduction, but nevertheless benefit because they obtain sons with superior
      manipulative abilities. Female defences against male manipulations may not be
      'imperfect' because of inability to keep pace with male evolution, but in order
      to screen males and favour those that are especially good manipulators. We
      examine the consequences of these ideas, and of the difficulties of obtaining
      biologically realistic measures of female costs, for some recent theoretical and
      empirical presentations of male-female conflict ideas, and find that male-female
      conflict in the new sense is less certain than has been commonly supposed.
      Disentangling previous sexual selection ideas and the new conflict of interest
      models will probably often be difficult, because the two types of payoffs are not
      mutually exclusive.

PMID- 14635876
TI  - A phallus for free? Quantitative genetics of sexual trade-offs in the snail
      Bulinus truncatus.
AB  - Resource allocation is thought to play a key role in the coexistence of different
      sexual morphs within hermaphroditic species. Indeed, most models assume that
      sexual functions are subject to a balance between reproductive advantage and
      energetic cost. Various types of cost (e.g. organ construction, maintenance and
      utilization) and levels of trade-off (physiological and genetic) may be
      considered. We here examine physiological and genetic costs of phallus
      construction and maintenance in Bulinus truncatus, a snail species in which
      aphallic individuals (without phallus) coexist with regular hermaphrodites. We
      use a quantitative genetic design involving 37 inbred lines (four populations)
      known to produce different proportions of aphallics, to test for the existence of
      genetic and nongenetic correlations between aphally and a range of life-history
      traits over the totality of the life cycle. Our results show that aphallic and
      euphallic individuals of the same line do not show consistent differences in
      either growth, fecundity (including offspring survival), or longevity.
      Furthermore, none of these traits is genetically correlated across lines with the
      frequency of the aphallic morph. We conclude that the cost of the construction
      and maintenance of the phallus must be very low in this species. Future studies
      should investigate the cost associated with using the phallus (i.e. male
      outcrossing behaviour) to explain the maintenance of high frequencies of aphallic
      individuals in natural populations.

PMID- 14635877
TI  - Closing of the Tethys Sea and the phylogeny of Eurasian killifishes
      (Cyprinodontiformes: Cyprinodontidae).
AB  - To test vicariant speciation hypotheses derived from geological evidence of the
      closing of the Tethys Sea, we reconstruct phylogenetic relationships of the
      predominantly fresh-water killifish genus Aphanius using 3263 aligned base pairs
      of mitochondrial DNA from samples representing 49 populations of 13 species. We
      use additional 11 cyprinodontid species as outgroup taxa. Genes analysed include
      those encoding the partial 12S and 16S ribosomal RNAs; transfer RNAs for valine,
      leucine, isoleucine, glutamine, methionine, tryptophan, alanine, asparagine,
      cysteine and tyrosine; and complete nicotinamide adenine dinucleotide
      dehydrogenase subunit I and II. Molecular substitution rate for this DNA region
      is estimated at of 8.6 +/- 0.1 x 10(-9) substitutions base pair(-1) year(-1), and
      is derived from a well dated transgression of the Red Sea into the Wadi Sirhan of
      Jordan 13 million years ago; an alternate substitution rate of 1.1 +/- 0.2 x 10(
      8) substitutions base pair(-1) year(-1) is estimated from fossil evidence.
      Aphanius forms two major clades which correspond to the former eastern and
      western Tethys Sea. Within the eastern clade Oligocene divergence into a fresh
      water clade inhabiting the Arabian Peninsula and an euhaline clade inhabiting
      coastal area from Pakistan to Somalia is observed. Within the western Tethys Sea
      clade we observe a middle Oligocene divergence into Iberian Peninsula and Atlas
      Mountains, and Turkey and Iran sections. Within Turkey we observe a large amount
      of genetic differentiation correlated with late Miocene orogenic events. Based on
      concordance of patterns of phylogenetic relationships and area relationships
      derived from geological and fossil data, as well as temporal congruence of these
      patterns, we support a predominantly vicariant-based speciation hypothesis for
      the genus Aphanius. An exception to this pattern forms the main clade of A.
      fasciatus, an euhaline circum-Mediterranean species, which shows little genetic
      differentiation or population structuring, thus providing no support for the
      hypothesis of vicariant differentiation associated with the Messinian Salinity
      Crisis. The two phylogenetically deepest events were also likely driven by
      ecological changes associated with the closing of the Tethys Sea.

PMID- 14635878
TI  - No evidence for parallel sympatric speciation in cichlid species of the genus
      Pseudotropheus from north-western Lake Malawi.
AB  - To test the hypothesis of parallel speciation by sexual selection, we examined
      length variation at six microsatellite loci of samples from four sites of four to
      six putative species belonging to two subgenera of rocky shore mbuna cichlids
      from Lake Malawi. Almost all fixation indices were significantly different from
      zero, suggesting that there is presently little or no gene flow among allopatric
      populations or sympatric species. Analysis of variance indicated that genetic
      distances among allopatric populations of putative conspecifics were
      significantly lower than among sympatric populations of heterospecifics. The
      topology of trees based on distance matrices was also largely consistent with the
      hypothesis that the putative species are monophyletic and have thus not evolved
      in parallel in their present locations. If parallel speciation does occur in
      Malawi cichlids, it may be on a larger spatial scale than investigated in our
      study.

PMID- 14635879
TI  - Optimal growth strategies of larval helminths in their intermediate hosts.
AB  - We consider optimal growth of larval stages in complex parasite life cycles where
      there is no constraint because of host immune responses. Our model predicts an
      individual's asymptotic size in its intermediate host, with and without
      competition from conspecific larvae. We match observed variations in larval
      growth patterns in pseudophyllid cestodes with theoretical predictions of our
      model. If survival of the host is vital for transmission, larvae should reduce
      asymptotic size as intensity increases, to avoid killing the host. The life
      history strategy (LHS) model predicts a size reduction <1/intensity, thus
      increasing the parasite burden on the host. We discuss whether body size of
      competing parasites is an evolved LHS or simply reflects resource constraints
      (RC) on growth fixed by the host, leading to a constant total burden with
      intensity. Growth under competition appears comparable with "the tragedy of the
      commons", much analysed in social sciences. Our LHS prediction suggests that
      evolution generates a solution that seems cooperative but is actually selfish.

PMID- 14635880
TI  - Phenotypic plasticity and the evolution of trade-offs: the quantitative genetics
      of resource allocation in the wing dimorphic cricket, Gryllus firmus.
AB  - In the wing dimorphic sand cricket, Gryllus firmus, there is a pronounced trade
      off between flight capability and fecundity. This trade-off is found both between
      morphs and within the macropterous morph, in which fecundity is negatively
      correlated with the mass of the principle flight muscles, the dorso-longitudinal
      muscles (DLM). In this paper, we examine how this trade-off is affected by a
      reduction in food and its genetic basis. We find that the relative fitness of the
      two wing morphs is not changed although both fecundity and DLM mass are
      decreased. A quantitative genetic analysis shows that the trade-off function is
      genetically variable but that most of the variation occurs in the intercept
      rather than the slope of the function. Analysis further indicates a very high
      genetic correlation between environments (food ration) supporting the hypothesis
      of a strong functional constraint between reproduction and flight capability.

PMID- 14635881
TI  - Levels of selection in positive-strand virus dynamics.
AB  - Conflicting selection pressures occurring over the life cycle of an organism
      constitute serious challenges to the robustness of replication. Viruses present a
      credible model system for analysing problems that arise through evolutionary
      conflicts of interest. We present a multi-level selection model for the life
      cycle of positive-strand RNA viruses. The model combines within-cell replication
      kinetics and protein synthesis, and between-cell population dynamics of virion
      production and transmission. We show how these two levels of within-host
      selection interact to produce tradeoffs in the life history strategy of a virus
      without consideration of host mortality. We find that viruses evolve towards
      intermediate rather than maximum encapsidation rates. This can be interpreted as
      selection for intermediate virulence through cellular persistence. We
      characterize a theoretical persistence threshold arising from the trade-off
      between genome replication and genetic translation within the cell. We present
      counter-intuitive relationships whereby increasing genome decay rates and rates
      of encapsidation lead to increases in the abundance of virus-encoded proteins.
      Data from poliovirus suggest that viruses might be unable to resolve the vertical
      conflicts of interests among different levels of selection.

PMID- 14635882
TI  - Heritability of resistance against ectoparasitism in the Drosophila-Macrocheles
      system.
AB  - Ectoparasites are abundant in natural communities, can have pronounced
      deleterious fitness consequences to their host and are important vectors of
      transmissible parasitic disease. Yet very few studies have estimated the
      magnitude of heritable genetic variation underlying resistance against
      ectoparasitism, which significantly limits our ability to predict the evolution
      of this ecologically important character. The present paper reports results of
      artificial selection for increased resistance in Drosophila nigrospiracula
      against ectoparasitic, haematophagous mites, Macrocheles subbadius. In this
      system, which occurs naturally in the Sonoran Desert of North America,
      ectoparasitism significantly damages the expression of host fitness traits,
      including longevity, fecundity and male mating success. In the present study,
      resistance, which was modelled as a threshold trait, responded significantly to
      selection applied on either sex. Realized heritability, calculated as a mean
      across four replicates, was estimated to be 0.152 +/- 0.014 (SE). The
      heritability estimate from selection on males did not differ from that on
      females, but both estimates differed significantly from zero. This documented
      presence of additive genetic variation for resistance, coupled with knowledge of
      the fitness consequences of ectoparasitism, indicates that the host population
      possesses significant evolutionary potential. Selection was applied on the pre
      attachment phase, thereby targeting behavioural forms of defence. This study
      therefore establishes parallels between insects and other animals in their
      ability to protect themselves and evolve behavioural defences against
      ectoparasites.

PMID- 14635883
TI  - Forty years of solitude: life-history divergence and behavioural isolation
      between laboratory lines of Drosophila melanogaster.
AB  - The study of the early stages of speciation can benefit from examination of
      differences between populations of known history that have been separated for a
      short time, such as a few thousands of generations. We asked whether two lines of
      Drosophila melanogaster that were isolated more than 40 years ago have evolved
      differences in life-history characters, or have begun to evolve behavioural or
      postzygotic isolation. One line, which is resistant to DDT, showed lower egg
      production and a shorter lifespan than a susceptible line. These differences are
      not a pleiotropic effect of resistance because they are not attributable to the
      chromosome that contains the resistance factors. The two lines have begun to
      become behaviourally isolated. Again, the isolation is not attributable to genes
      on the chromosome that contains resistance factors. The lines show only
      prezygotic isolation; there is no evidence of reduced fitness of F1 or F2
      hybrids. These lines and others like them, should be excellent subjects for
      analyses of genetic changes that could lead to speciation.

PMID- 14635884
TI  - Proximate mechanisms of variation in the carotenoid-based plumage coloration of
      nestling great tits (Parus major L.).
AB  - Many vertebrates use carotenoid-based signals in social or sexual interactions.
      Honest signalling via carotenoids implies some limitation of carotenoid-based
      colour expression among phenotypes in the wild, and at least five limiting
      proximate mechanisms have been hypothesized. Limitation may arise by carotenoid
      availability, genetic constraints, body condition, parasites, or detrimental
      effects of carotenoids. An understanding of the relative importance of the five
      mechanisms is relevant in the context of natural and sexual selection acting on
      signal evolution. In an experimental field study with carotenoid supplementation,
      simultaneous cross-fostering, manipulation of brood size and ectoparasite load,
      we investigated the relative importance of these mechanisms for the variation in
      carotenoid-based coloration of nestling great tits (Parus major). Carotenoid
      based plumage coloration was significantly related to genetic origin of
      nestlings, and was enhanced both in carotenoid-supplemented nestlings, and
      nestlings raised in reduced broods. We found a tendency for ectoparasite-induced
      limitation of colour expression and no evidence for detrimental effects of
      carotenoids on growth pattern, mortality and recruitment of nestlings to the
      local breeding population. Thus, three of the five proposed mechanisms can
      generate individual variation in the expression of carotenoid-based plumage
      coloration in the wild and thus could maintain honesty in a trait potentially
      used for signalling of individual quality.

PMID- 14635885
TI  - Fluctuating asymmetry in a secondary sexual trait: no associations with
      individual fitness, environmental stress or inbreeding, and no heritability.
AB  - It has been suggested that fluctuating asymmetry (FA) in secondary sexual traits
      may be a useful indicator of either individual quality or environmental stress.
      We tested this concept using a series of analyses of FA in male antler size in a
      wild red deer (Cervus elaphus) population, using four measures of size repeated
      across successive years on the same individuals. We found no consistent evidence
      of correlations between traits in levels of FA, nor of any associations between
      known environmental or developmental conditions. None of the four measures of FA
      showed a significant heritability (average h2 = 0.041), nor was there any
      evidence of inbreeding depression. For three of the four traits, fluctuating
      asymmetry did not predict either annual or lifetime breeding success. However
      there were significant associations between breeding success and FA in antler
      length. Given the series of null results in our other tests, it seems likely that
      this was a direct mechanistic effect rather than because measures of FA were
      indicative of individual quality or condition.

PMID- 14635886
TI  - Functional significance of seminal receptacle length in Drosophila melanogaster.
AB  - Despite its central role in post-copulatory sexual selection, the female
      reproductive tract is poorly understood. Here we provide the first experimental
      study of the adaptive significance of variation in female sperm-storage organ
      morphology. Using populations of Drosophila melanogaster artificially selected
      for longer or shorter seminal receptacles, we identify relationships between the
      length of this primary sperm-storage organ and the number of sperm stored,
      pattern of progeny production, rate of egg fertilization, remating interval, and
      pattern of sperm precedence. Costs and benefits of relatively short or long
      organs were identified. Benefits of longer receptacles include increased sperm
      storage capacity and thus progeny production from a single insemination. Results
      suggest that longer receptacles have not naturally evolved because of
      developmental time costs and a correlated reduction in longevity of mated
      females. This latter cost may be a consequence of sexual conflict mediated by
      ejaculate toxicity. Receptacle length did not alter the pattern of sperm
      precedence, which is consistent with data on the co-evolution of sperm and female
      receptacle length, and a pattern of differential male fertilization success being
      principally determined by the interaction between these male and female traits.

PMID- 14635887
TI  - Evolutionary ecology of Datura stramonium: equal plant fitness benefits of growth
      and resistance against herbivory.
AB  - This study evaluated how natural selection act upon two proposed alternatives of
      defence (growth and resistance) against natural enemies in a common garden
      experiment using genetic material (full-sibs) from three populations of the
      annual plant Datura stramonium. Genetic and phenotypic correlations were used to
      search for a negative association between both alternatives of defence. Finally,
      the presence/absence of natural enemies was manipulated to evaluate the selective
      value of growth as a response against herbivory. Results indicated the presence
      of genetic variation for growth and resistance (1--relative damage), whereas only
      population differentiation for resistance was detected. No correlation between
      growth and resistance was detected either at the phenotypic or the genetic level.
      Selection analysis revealed the presence of equal fitness benefits of growth and
      resistance among populations. The presence/absence of natural herbivores revealed
      that herbivory did not alter the pattern of selection on growth. The results
      indicate that both strategies of defence can evolve simultaneously within
      populations of D. stramonium.

PMID- 14635888
TI  - Genetic variation of polygenic characters and the evolution of genetic
      degeneracy.
AB  - The classical model of mutation-selection balance for quantitative characters
      sums the effects of individual sites to determine overall character value. I
      develop an alternative version of this classical model in which character value
      depends on the averaging of the effects of the individual sites. In this new
      averaging model, the equilibrium patterns of variance in allelic effects and
      character values change with the number of sites that affect a character in a
      different way from the classical model of summing effects. Besides changing the
      patterns of variance, the averaging model favours the addition of loci to the
      control of character values, perhaps explaining in part the recent observation of
      widespread genetic degeneracy.

PMID- 14635889
TI  - Evolution of dispersal in metapopulations with local density dependence and
      demographic stochasticity.
AB  - In this paper, we predict the outcome of dispersal evolution in metapopulations
      based on the following assumptions: (i) population dynamics within patches are
      density-regulated by realistic growth functions; (ii) demographic stochasticity
      resulting from finite population sizes within patches is accounted for; and (iii)
      the transition of individuals between patches is explicitly modelled by a
      disperser pool. We show, first, that evolutionarily stable dispersal rates do not
      necessarily increase with rates for the local extinction of populations due to
      external disturbances in habitable patches. Second, we describe how demographic
      stochasticity affects the evolution of dispersal rates: evolutionarily stable
      dispersal rates remain high even when disturbance-related rates of local
      extinction are low, and a variety of qualitatively different responses of adapted
      dispersal rates to varied levels of disturbance become possible. This paper
      shows, for the first time, that evolution of dispersal rates may give rise to
      monotonically increasing or decreasing responses, as well as to intermediate
      maxima or minima.

PMID- 14635890
TI  - Sexual size dimorphism and timing of spring migration in birds.
AB  - Sexually selected traits are limited by selection against those traits in other
      fitness components, such as survival. Thus, sexual selection favouring large size
      in males should be balanced by higher mortality of larger males. However,
      evidence from red-winged blackbirds (Agelaius phoeniceus) indicates that large
      males survive better than small males. A survival advantage to large size could
      result from males migrating north in early spring, when harsh weather favours
      large size for energetic reasons. From this hypothesis we predicted that, among
      species, sex differences in body size should be correlated with sex differences
      in timing of spring migration. The earlier males migrate relative to females, the
      larger they should be relative to females. We tested this prediction using a
      comparative analysis of data collected from 30 species of passerine birds
      captured on migration. After controlling for social mating system, we found that
      sexual size dimorphism and difference in arrival dates of males and females were
      significantly positively correlated. This result is consistent with the
      hypothesis that selection for survival ability promotes sexual size dimorphism
      (SSD), rather than opposes SSD as is the conventional view. If both natural
      selection and sexual selection favour large adult males, then limits to male size
      must be imposed before males become adults.

PMID- 14635891
TI  - Gradual and quantum genome size shifts in the hystricognath rodents.
AB  - We assessed genome size variation by flow cytometry within and among 31 species
      of nine families of African and South American hystricognath rodents.
      Interspecific variation was extensive and genome size was relatively high among
      the South American radiation whereas only moderate variation and smaller
      estimates of genome size were observed in the African counterparts. The largest
      genome size, indicating tetraploidy was recorded in the South American
      octodontid, Tympanoctomys barrerae (16.8 pg DNA). This quantum shift in DNA
      content represents a novel mechanism of genome evolution in mammals. As expected
      in polyploid organisms, varying nucleotypic effects were observed in the
      dimensions of the sperm cells and lymphocytes of T. barrerae. The role of control
      mechanisms that influence cell dimensions in polyploid organisms is discussed.

PMID- 14635892
TI  - A potential mechanism for cryptic female choice in a flour beetle.
AB  - In polyandrous mating systems, events occurring during copulation can alter the
      fate of the mating male's sperm. These events may exert selective pressures
      resulting in the evolution of diverse reproductive behaviours, morphologies and
      physiologies. This study investigates the role of male and female copulatory
      behaviours on sperm fate in the red flour beetle, Tribolium castaneum. I describe
      and quantify copulatory behaviours for mating pairs, and examine sperm fate by
      quantifying sperm transfer, sperm storage and second male sperm precedence.
      Whereas female quiescence during copulation and male leg rubbing during
      copulation together account for significant variation (26%) in sperm precedence,
      female copulatory quiescence alone provides information about the timing and
      numbers of sperm transferred. These experiments show that a female copulatory
      behaviour predicts sperm fate, and emphasize the value of studying variation in
      both male and female copulatory behaviours for understanding factors affecting
      sperm use.

PMID- 14635893
TI  - Sequential radiation of unrelated organisms: the gall fly Eurosta solidaginis and
      the tumbling flower beetle Mordellistena convicta.
AB  - Host shifts and the formation of insect-host races are likely common processes in
      the speciation of herbivorous insects. The interactions of goldenrods Solidago
      (Compositae), the gall fly Eurosta solidaginis (Diptera: Tephritidae) and the
      beetle Mordellistena convicta (Coleoptera: Mordellidae) provide behavioural,
      ecological and genetic evidence of host races that may represent incipient
      species forming via sympatric speciation. We summarize evidence for Eurosta host
      races and show that M. convicta has radiated from goldenrod stems to Eurosta
      galls to form host-part races and, having exploited the galler's host shift, has
      begun to differentiate into host races within galls. Thus, host-race formation
      has occurred in two interacting, but unrelated organisms representing two trophic
      levels, resulting in 'sequential radiation' (escalation of biodiversity up the
      trophic system). Distributions of host races and their behavioural isolating
      mechanisms suggest sympatric differentiation. Such differentiation suggests host
      race formation and subsequent speciation may be an important source of
      biodiversity.

PMID- 14635894
TI  - Evidence for male-biased effective sex ratio and recent step-by-step colonization
      in the bivalve Pinctada mazatlanica.
AB  - This paper presents a comparison of the geographical distribution of genetic
      variability at mitochondrial and nuclear loci among pearl oyster populations from
      the tropical American Pacific coast (Pinctada mazatlanica). Surprisingly, both
      mitochondrial and nuclear gene variability decreased regularly from north to
      south of the studied area, which, altogether with a significant correlation
      between genetic and geographical distances for mtDNA, suggests a recent
      colonization or re-colonization of the southern areas. However, the loss of
      diversity between north and south was much more important for mitochondrial than
      for nuclear DNA, and this did not translate into measurable fixation index at
      nuclear loci (theta = 0.03, n.s.), contrary to the mitochondrial data (theta =
      0.18*). Smaller effective size of mtDNA accentuated by a strong male-biased
      effective sex ratio and step-by-step colonization from northern areas can explain
      this discrepancy among natural populations of this protandric species.

PMID- 14635895
TI  - Fitness effects of female mate choice: preferred males are detrimental for
      Drosophila melanogaster females.
AB  - The evolution of female mate choice, broadly defined to include any female
      behaviour or morphology which biases matings towards certain male phenotypes, is
      traditionally thought to result from direct or indirect benefits which females
      acquire when mating with preferred males. In contrast, new models have shown that
      female mate choice can be generated by sexual conflict, where preferred males may
      cause a fitness depression in females. Several studies have shown that female
      Drosophila melanogaster bias matings towards large males. Here, we use male size
      as a proxy for male attractiveness and test how female fitness is affected by
      reproducing with large or small males, under two different male densities.
      Females housed with large males had reduced lifespan and aged at an accelerated
      rate compared with females housed with small males, and increased male density
      depressed female fitness further. These fitness differences were due to effects
      on several different fitness components. Female fitness covaried negatively with
      male courtship rate, which suggests a cost of courtship. Mating rate increased
      with male size, whereas female fitness peaked at an intermediate mating rate. Our
      results suggest that female mate choice in D. melanogaster is, at least in part,
      a by-product of sexual conflict over the mating rate.

PMID- 14635896
TI  - Rates of deleterious mutation and the evolution of sex in Caenorhabditis.
AB  - A variety of models propose that the accumulation of deleterious mutations plays
      an important role in the evolution of breeding systems. These models make
      predictions regarding the relative rates of protein evolution and deleterious
      mutation in taxa with contrasting modes of reproduction. Here we compare
      available coding sequences from one obligately outcrossing and two primarily
      selfing species of Caenorhabditis to explore the potential for mutational models
      to explain the evolution of breeding system in this clade. If deleterious
      mutations interact synergistically, the mutational deterministic hypothesis
      predicts that a high genomic deleterious mutation rate (U) will offset the
      reproductive disadvantage of outcrossing relative to asexual or selfing
      reproduction. Therefore, C. elegans and C. briggsae (both largely selfing) should
      both exhibit lower rates of deleterious mutation than the obligately outcrossing
      relative C. remanei. Using a comparative approach, we estimate U to be equivalent
      (and < 1) among all three related species. Stochastic mutational models, Muller's
      ratchet and Hill-Robertson interference, are expected to cause reductions in the
      effective population size in species that rarely outcross, thereby allowing
      deleterious mutations to accumulate at an elevated rate. We find only limited
      support for more rapid molecular evolution in selfing lineages. Overall, our
      analyses indicate that the evolution of breeding system in this group is unlikely
      to be explained solely by available mutational models.

PMID- 14635897
TI  - When to be born? Prolonged pregnancy or incubation enhances locomotor performance
      in neonatal lizards (Scincidae).
AB  - The degree of offspring development at hatching (or birth) varies among species
      within most major vertebrate lineages; altricial vs. precocial birds offer the
      clearest example of a trade-off between early hatching and the degree of
      locomotor development of the hatchling. No such diversity has been reported for
      reptiles, but we suggest that natural selection may fine-tune the time of
      hatching (in oviparous species) or birth (in viviparous species) to optimize
      offspring phenotypes and hence, maximize fitness. This hypothesis predicts
      enhanced neonatal performance after more prolonged incubation or gestation,
      within as well as among populations. Both published and original data on
      Australian scincid lizards support this prediction. In a field study, viviparous
      alpine skinks (Niveoscincus microlepidotus) that gave birth later in the season
      had faster-running offspring, that had a higher probability of surviving through
      the first year of life. The enhanced performance and survival were not secondary
      results of larger offspring size. After controlling for effects of mean
      incubation temperature, prolonged development also correlated with enhanced
      locomotor performance in hatchlings from eggs of an oviparous skink (Bassiana
      duperreyi) incubated at warm temperatures (> 20 degrees C) but not at cooler
      temperatures (< 20 degrees C). We suggest that embryonic reptiles control their
      date of hatching or birth and thus, their stage of development at this critical
      life-history transition.

PMID- 14635898
TI  - Incongruent nuclear and mitochondrial phylogeographic patterns in the Timarcha
      goettingensis species complex (Coleoptera, Chrysomelidae).
AB  - Phylogeographic analyses have mostly been based on single-gene genealogies but it
      is unclear how conclusions from such studies depend on the choice of gene
      markers. We conducted a nested geographical clade analysis [A.R. Templeton, E.
      Routman and C.A. Phillips (1995) Genetics 140: 767-782] based on nuclear rDNA
      internal transcribed spacer region 2 (ITS2) sequences in the Timarcha
      goettingensis species complex (Coleoptera, Chrysomelidae), and compared the
      inferences with an updated version of previously published results using
      mitochondrial cytochrome oxidase II (COIl) sequences. Inferences from ITS2
      suggest that patterns of marker distribution are mostly explained by restricted
      gene flow with isolation by distance. In contrast, COII revealed a history of
      geographical structure resulting from episodic population contiguous-range
      expansions. Both markers also show different genealogical patterns, which are
      associated to the effects of genetic introgression in a putative hybrid zone
      between two major lineages in the complex. Altogether, these differences are
      attributed to distinct population and/or evolutionary dynamics of the markers,
      and offer a more accurate phylogeographic description for the T. goettingensis
      complex.

PMID- 14635899
TI  - The relationship between multiple mating by queens, within-colony genetic
      variability and fitness in the ant Lasius niger.
AB  - Multiple mating has been suggested to benefit social insect queens because high
      genetic variation within colonies might decrease the load imposed by sterile
      diploid males, enhance resistance to parasites and pathogens, and lead to a more
      effective division of labour and/or a wider range of tolerable environmental
      conditions. We tested these hypotheses in the ant Lasius niger with three
      population samples from Switzerland and Sweden. We found no diploid males in
      young or mature colonies suggesting a lack of diploid male load. Colonies with
      multiply-mated queens were not larger nor did they produce more sexuals than
      colonies with singly-mated queens. We did find a significantly lower frequency of
      multiple mating among newly mated queens than among the queens heading mature
      colonies in one population sample (Switzerland 1997). However, this result was
      not repeated in the other study population, or in the following year in the Swiss
      population.

PMID- 14635900
TI  - Sex-specific associative learning cues and inclusive fitness benefits in the
      Seychelles warbler.
AB  - In cooperative breeding vertebrates, indirect fitness benefits would be maximized
      by subordinates that accurately assess their relatedness to group offspring and
      preferentially help more closely related kin. In the Seychelles warbler
      (Acrocephalus sechellensis), we found a positive relationship between subordinate
      nestling kinship (determined using microsatellite marker genotypes) and
      provisioning rates, but only for female subordinates. Female subordinates that
      helped were significantly more related to the nestlings than were nonhelpers, and
      the decision to help appears to be based on associative learning cues. High
      levels of female infidelity means that subordinates cannot trust their legitimacy
      through the male line, consequently they appear to use the continued presence of
      the primary female, but not the primary male, as a reliable cue to determine when
      to feed nestlings. By using effective discrimination, female subordinates are
      able to maximize the indirect benefits gained within a cooperative breeding
      system otherwise driven primarily by direct breeding benefits.

PMID- 14635901
TI  - Fitness-associated recombination on rugged adaptive landscapes.
AB  - A negative correlation between fitness and recombination rates seems to exist in
      various organisms. In this article we suggest that a correlation of that kind may
      play an important role in the evolution of complex traits. We study the effects
      of such fitness-associated recombination (FAR) in a simple two-locus
      deterministic model, as well as in a multi-loci NK rugged adaptive landscape. In
      both models studied, FAR results in faster adaptation and higher average
      population fitness, compared with uniform-rate recombination.

PMID- 14635902
TI  - Testing paleolimnological predictions with molecular data: the origins of
      Holarctic Eubosmina.
AB  - Zooplankton of the family Bosminidae have a unique paleolimnological record in
      many Holarctic lakes that provides a near continuous record of morphological
      change for thousands of years. If this morphological change could be interpreted
      reliably, then a rarely achieved direct observation of macroevolution would be
      feasible. We tested paleolimnological predictions derived from morphological
      variation found in the genus Eubosmina using mtDNA and nuclear DNA sequence
      variation from geographically distant Holarctic sites. The mtDNA and nDNA trees
      were congruent but genetic divergence was inversely associated with morphological
      divergence. The three most genetically divergent groups belonged to Eubosmina
      longispina, whose phylogeography and genetic divergence was consistent with
      glacial vicariance. The genetic evidence also supported the hypothesis that at
      least two Nearctic species were recent European introductions. Finally, the
      genetic evidence was consistent with paleolimnology in the finding of several
      proposed species undergoing rapid morphological evolution and being post
      glacially derived from European E. longispina. The results suggested that
      lacustrine bosminids are susceptible to geographic speciation processes, and that
      morphological interpretation of diversity in paleolimnology can be markedly
      improved by genetic studies.

PMID- 14635903
TI  - Genetic architecture for normal and novel host-plant use in two local populations
      of the herbivorous ladybird beetle, Epilachna pustulosa.
AB  - Trade-offs in host-plant use are thought to promote the evolution of host
      specificity. However, usually either positive or no genetic correlations have
      been found. Whereas factors enhancing variation in overall viability have been
      claimed to mask negative genetic correlations, alternative hypotheses emphasize
      the sequential changes in genetic correlation in the course of host-range
      evolution. In this study, the genetic architectures of performances on different
      hosts were compared in two populations of the herbivorous ladybird beetle,
      Epilachna pustulosa, using three host plants, one being normal for both, one
      novel for only one population, and the other novel for both populations. The
      genetic correlations between larval periods on normal hosts were significantly
      positive whereas those between normal and novel hosts were not different from
      zero. There was no evidence for reduced genetic variation on the normal host
      plants. These results suggest that the host-range is not restricted by the
      antagonistic genetic associations among exploitation abilities on different plant
      species, but rather that selection of different host-plants may improve the
      coordination between genes responsible for the use of different plants.

PMID- 14635904
TI  - Sexually selected nest-building--Pomatoschistus minutus males build smaller nest
      openings in the presence of sneaker males.
AB  - Both natural selection and sexual selection may act on nest-building. We tested
      experimentally how different regimes of egg-predation and male-male competition
      influence nest-building before mating, using the marine fish sand goby,
      Pomatoschistus minutus. Males with sneaker males present built the smallest nest
      openings, smaller than males held alone or with Pomatoschistus microps males
      (which may predate eggs and compete over nest-sites but not compete over
      fertilizations). Males with visual access to other nest-building males tended
      also to build smaller openings than males held alone or with P. microps. Males
      with egg-predators present built nests with openings not differing significantly
      from any other treatment. Our results indicate that the small nest-openings found
      in the sneaker male treatment are sexually selected through protection against
      sneaking or by female choice. Across treatments, time span before a male started
      to build his nest also explained variation in nest-opening width; males starting
      late built larger nest-openings.

PMID- 14635905
TI  - Sexual selection on morphological and physiological traits and fluctuating
      asymmetry in the yellow dung fly.
AB  - Previous univariate studies of the yellow dung fly (Scathophaga stercoraria) have
      demonstrated strong sexual selection, in terms of mating success, on male size
      (estimated as hind tibia length). To identify specific target(s) of selection on
      body size and possible conflicting selection pressures on particular body parts,
      two multivariate field studies of sexual selection were conducted. In one study
      using point samples from three populations, we assessed several morphological
      traits, including genital traits and measures of fluctuating asymmetry (FA) of
      all paired traits. There was sexual selection for large male size in general,
      confirming previous, univariate studies. With the possible exception of thorax
      width, which was selected in the opposite direction, no main target of selection
      was identified, as most morphological traits were highly correlated. There was no
      detectable sexual selection on the male external genital structures assessed. In
      a second study using multiple samples from one population, we included
      physiological measures of energy reserves (lipids, glucose and glycogen) known to
      affect mating success, in addition to trait size and FA of wings and legs.
      Inclusion of physiological traits is rare in phenomenological studies of
      selection. This study again confirmed the mating advantage of large males, and
      additionally showed independent positive influences of lipid and glucose but not
      glycogen levels. FA in paired traits generally did not affect male mating
      success, but was negatively correlated with energy reserves. Our study suggests
      that inclusion of physiological measures and genital traits in phenomenological
      studies of selection would be fruitful in other species.

PMID- 14635906
TI  - Male fitness of honeybee colonies (Apis mellifera L.).
AB  - Honeybees (Apis mellifera L.) have an extreme polyandrous mating system. Worker
      offspring of 19 naturally mated queens was genotyped with DNA microsatellites, to
      estimate male reproductive success of 16 drone producing colonies. This allowed
      for estimating the male mating success on both the colony level and the level of
      individual drones. The experiment was conducted in a closed population on an
      isolated island to exclude interferences of drones from unknown colonies.
      Although all colonies had produced similar numbers of drones, differences among
      the colonies in male mating success exceeded one order of magnitude. These
      differences were enhanced by the siring success of individual drones within the
      offspring of mated queens. The siring success of individual drones was correlated
      with the mating frequency at the colony level. Thus more successful colonies not
      only produced drones with a higher chance of mating, but also with a
      significantly higher proportion of offspring sired than drones from less
      successful colonies. Although the life cycle of honeybee colonies is very female
      centred, the male reproductive success appears to be a major driver of natural
      selection in honeybees.

PMID- 14635907
TI  - Constant relative age and size at sex change for sequentially hermaphroditic
      fish.
AB  - A general problem in evolutionary biology is that quantitative tests of theory
      usually require a detailed knowledge of the underlying trade-offs, which can be
      very hard to measure. Consequently, tests of theory are often constrained to be
      qualitative and not quantitative. A solution to this problem can arise when life
      histories are viewed in a dimensionless way. Recently, dimensionless theory has
      been developed to predict the size and age at which individuals should change
      sex. This theory predicts that the size at sex change/maximum size (L50/L(max)),
      and the age at sex change/age at first breeding (tau/alpha) should both be
      invariant. We found support for these two predictions across 52 species of fish.
      Fish change sex when they are 80% of their maximum body size, and 2.5 times their
      age at maturity. This invariant result holds despite a 60 and 25 fold difference
      across species in maximum size and age at sex change. These results suggest that,
      despite ignoring many biological complexities, relatively simple evolutionary
      theory is able to explain quantitatively at what point sex change occurs across
      fish species. Furthermore, our results suggest some very broad generalities in
      how male fitness varies with size and age across fish species with different
      mating systems.

PMID- 14635908
TI  - Directional changes in sexual size dimorphism in shorebirds, gulls and alcids.
AB  - The Charadrii (shorebirds, gulls and alcids) are one of the most diverse avian
      groups from the point of view of sexual size dimorphism, exhibiting extremes in
      both male-biased and female-biased dimorphism, as well as monomorphism. In this
      study we use phylogenetic comparative analyses to investigate how size dimorphism
      has changed over evolutionary time, distinguishing between changes that have
      occurred in females and in males. Independent contrasts analyses show that both
      body mass and wing length have been more variable in males than in females.
      Directional analyses show that male-biased dimorphism has increased after
      inferred transitions towards more polygynous mating systems. There have been
      analogous increases in female-biased dimorphism after transitions towards more
      socially polyandrous mating systems. Changes in dimorphism in both directions are
      attributable to male body size changing more than female body size. We suggest
      that this might be because females are under stronger natural selection
      constraints related to fecundity. Taken together, our results suggest that the
      observed variation in dimorphism of Charadrii can be best explained by male body
      size responding more sensitively to variable sexual selection than female body
      size.

PMID- 14635909
TI  - Morphological and microsatellite differentiation in Melospiza melodia (Aves) at a
      microgeographic scale.
AB  - Geographical variation in microsatellite allele frequencies and morphology were
      compared for five subspecies of Melospiza melodia (song sparrow; M. m. samuelis,
      M. m. maxillaris, M. m. pusillula, M. m. gouldii, and M. m. heermanni) in 14
      populations in the San Francisco Bay region to (a) assess divergence based on
      these estimates and (b) test the hypothesis that drift is responsible for
      morphological and genetic divergence. Morphological differentiation between
      subspecies was high despite low differentiation at microsatellite loci,
      indicating high gene flow and large effective population sizes. Low concordance
      of morphological and genetic estimates of divergence suggests that selection or
      phenotypic plasticity in morphology has caused morphological differentiation
      among the subspecies.

PMID- 14635910
TI  - Social competition, corticosterone and survival in female lizard morphs.
AB  - We examined the selective consequences of variation in behaviour and endocrine
      physiology in two female throat-colour morphs of the lizard, Uta stansburiana in
      the wild. Female morphs differed in home-range distribution patterns and
      corticosterone levels in relation to the density and frequency of their female
      neighbours. Levels of plasma corticosterone of yellow-throated females increased
      with increased density of both morphs. In contrast, orange-throated females had
      reduced levels of corticosterone in response to increased density of orange
      females. Additionally, females with lower corticosterone survived poorly,
      suggesting that social interactions and high local densities of orange females
      may be potentially costly for orange females. These results are consistent with
      decreased fitness effects and suppression of immune function previously reported
      for orange female morphs surrounded by more orange neighbours. These
      correlations, in conjunction with previous work in this system, indicate that
      corticosterone is likely to be an important physiological mechanism regulating
      female fitness in nature.

PMID- 14635911
TI  - Weak phylogenetic effects on ecological niches of Sylvia warblers.
AB  - To understand the evolution of ecological niches it is important to know whether
      niche evolution is constrained by phylogeny. We approached this question for
      Sylvia warblers by testing if closely related species are more similar in 20
      ecologically relevant morphological traits than distantly related species.
      Phylogenetic relatedness was quantified using a molecular phylogeny based on the
      mitochondrial cytochrome b gene. By Principal Component Analysis (PCA) two major
      niche axes were extracted. We tested the individual ecomorphological traits and
      the positions of the species on the PCA axes for phylogenetic effects using
      Mantel tests. The results demonstrated small but significant phylogenetic effects
      only for the length of the middle toe, a trait probably correlated with
      locomotion. In general, however, phylogenetic effects were very weak. This
      suggests that ecological niches in passerine birds have the potential to evolve
      rapidly and are not subject to major phylogenetic constraints.

PMID- 14635912
TI  - Structure and evolution of the horizontal septum in vertebrates.
AB  - Although the horizontal septum (HS) has been identified as playing a role in fish
      biomechanics and in path finding of cells during zebrafish development, its
      morphology is poorly known. However, it is generally regarded as an
      evolutionarily conserved structure. To test this idea, we applied a novel
      combination of techniques to analyse the HS of 35 species from all major
      gnathostome clades in which is visualized its collagen fibre architecture.
      Results show that the HS is a conserved trait only with respect to the presence
      of caudolateral [= epicentral] and craniolateral [= posterior oblique] collagen
      fibre tracts, but differs remarkably with respect to the specifications of these
      tracts. Our data revealed several evolutionary changes within vertebrates. In the
      gnathostome ancestor, the two tracts are represented by evenly distributed
      epicentral fibres (ECFs) and posterior oblique fibres (POFs). ECFs are condensed
      to distinct epicentral tendons (ECTs) in the actinopteran ancestor. POFs
      independently evolved to distinct posterior oblique tendons (POTs) at least two
      times within teleosts. Within basal teleostomes, POFs as well as ECFs or ECTs
      were lost two times independently. POTs were lost at least three times
      independently within teleosts. This view of a homoplastic HS remains stable
      regardless of the competing phylogenies used for analysis. Our data make
      problematic any generalization of biomechanical models on fish swimming that
      include the HS. They indicate that the pathfinding role of the HS in zebrafish
      may be extended to gnathostome fishes, but not to agnathans, sarcopterygian
      fishes and tetrapods.

PMID- 14635913
TI  - The effects of parasitism and inbreeding on the competitive ability in Daphnia
      magna: evidence for synergistic epistasis.
AB  - Synergistic epistasis for fitness is often assumed in models of how selection
      acts on the frequency and distribution of deleterious mutations. Evidence for
      synergistic epistasis would exist if the logarithm of fitness declines more
      quickly with number of deleterious mutations, than predicted by a linear decline.
      This can be studied indirectly by quantifying the effect of different levels of
      inbreeding on fitness. Here, six sets (different genetic backgrounds) of three
      increasingly inbred Daphnia magna clones were used to assess their relative
      fitness according to changes in frequency in a competition experiment against a
      tester clone. A novelty of the mating procedure was that the inbreeding
      coefficients (F) of the three clones belonging to each set increased in steps of
      0.25 independent of the (unknown) inbreeding coefficient of the common ancestor.
      The equal increase of the inbreeding coefficients is important, because
      deviations influence the quantification of inbreeding depression, its variance
      and the detection of epistasis. In a simple mathematical model we show that when
      working with a partially inbred population inbreeding depression is
      underestimated, the variance of fitness is increased, and the detection of
      epistasis more difficult. Further, to examine whether an interaction between
      inbreeding and parasitism exists, each inbred clone was tested with and without a
      microsporidium infection (Octosporea bayeri). We found a nonlinear decrease of
      the logarithm of fitness across the three levels of inbreeding, indicating
      synergistic epistasis. The interaction term between parasitism and inbreeding was
      not significant. Our results suggest that deleterious mutations may be purged
      effectively once the level of inbreeding is high, but that parasitism seems not
      to influence this effect.

PMID- 14635914
TI  - Adaptive sex-specific life history plasticity to temperature and photoperiod in a
      damselfly.
AB  - We investigated four predictions about how temperature, photoperiod and sex
      affect the life history plasticity and foraging activity of a damselfly. (i) As
      predicted, increased temperatures increased foraging activity and growth rates,
      but in contrast with the prediction, late photoperiod (high time stress) did not
      affect foraging activity and growth rate. (ii) Unexpectedly, the increase in
      growth rate at increasing temperatures was not larger under high time stress.
      (iii) As predicted, age and size at emergence decreased at higher temperatures
      and at the late photoperiod. Temperature-induced life history shifts were direct
      or the result of behavioural growth mediation depending on the temperature range.
      Photoperiod-induced life history shifts were direct. (iv) As predicted, males
      emerged before females but at a smaller size. The degree of sexual size
      dimorphism was influenced by the joint effects of temperature and photoperiod. We
      could only detect genetic variation in size plasticity to photoperiod. The match
      between the sex-specific life history responses to temperature and photoperiod
      and predictions by relevant optimality models suggests adaptive life history
      plasticity to these variables.

PMID- 14635915
TI  - Latitudinal countergradient variation in the common frog (Rana temporaria)
      development rates--evidence for local adaptation.
AB  - Adaptive genetic differentiation along a climatic gradient as a response to
      natural selection is not necessarily expressed at phenotypic level if
      environmental effects on population mean phenotypes oppose the genotypic effects.
      This form of cryptic evolution--called countergradient variation--has seldom been
      explicitly demonstrated for terrestrial vertebrates. We investigated the patterns
      of phenotypic and genotypic differentiation in developmental rates of common
      frogs (Rana temporaria) along a ca. 1600 km latitudinal gradient across
      Scandinavia. Developmental rates in the field were not latitudinally ordered, but
      displayed large variation even among different ponds within a given latitudinal
      area. In contrast, development rates assessed in the laboratory increased
      strongly and linearly with increasing latitude, suggesting a genetic capacity for
      faster development in the northern than the southern larvae. Experiments further
      revealed that environmental effects (temperature and food) could easily override
      the genetic effects on developmental rates, providing a possible mechanistic
      explanation as to why the genetic differentiation was not seen in the samples
      collected from the wild. Our results suggest that the higher developmental rates
      of the northern larvae are likely to be related to selection stemming from
      seasonal time constrains, rather than from selection dictated by low ambient
      temperatures per se. All in all, the results provide a demonstration of
      environmental effects concealing substantial latitudinally ordered genetic
      differentiation understandable in terms of adaptation to clinal variation in time
      constrains.

PMID- 14635916
TI  - Phylogenetic analysis of the ecological correlates of dioecy in angiosperms.
AB  - We report on a phylogenetic analysis of correlations between the occurrence of
      dioecy and several ecological and life-history attributes: tropical distribution,
      woody growth form, abiotic pollination, small inconspicuous flowers and
      inflorescences, many-flowered inflorescences and fleshy fruits. Various
      hypotheses have been proposed to explain why associations occur between dioecy
      and several of these attributes, yet most assume that dioecy originates more
      often in clades with these traits than in clades with alternative character
      states. To investigate correlations between dioecy and these attributes, and to
      provide insights into the potential evolutionary pathways that have led to these
      associations, we assigned states of these traits to genera on a large-scale
      molecular phylogeny of the angiosperms; we then used maximum-likelihood analysis
      to analyse the presence of correlations and the sequence of acquisition of
      traits. Phylogenetic analysis revealed correlations between dioecy and six of the
      seven attributes; only many-flowered inflorescences exhibiting no association
      with the dioecious condition. The particular correlations that were revealed and
      the strength of the association differed among the three main monophyletic groups
      of angiosperms (Rosids, Asterids, and Eumagnoliids). Our analysis provided no
      general support for the hypothesis that dioecy is more likely to evolve in
      lineages already possessing the seven attributes we considered. Further analysis
      of the intercorrelations of the seven attributes provided evidence for non
      independence between some of the traits, implying that functional associations
      among these traits have influenced the ecology and evolution of dioecious
      species.

PMID- 14635917
TI  - Chloroplast DNA indicates a single origin of the allotetraploid Arabidopsis
      suecica.
AB  - DNA sequencing was performed on up to 12 chloroplast DNA regions [giving a total
      of 4288 base pairs (bp) in length] from the allopolyploid Arabidopsis suecica (48
      accessions) and its two parental species, A. thaliana (25 accessions) and A.
      arenosa (seven accessions). Arabidopsis suecica was identical to A. thaliana at
      all 93 sites where A. thaliana and A. arenosa differed, thus showing that A.
      thaliana is the maternal parent of A. suecica. Under the assumption that A.
      thaliana and A. arenosa separated 5 million years ago, we estimated a
      substitution rate of 2.9 x 10(-9) per site per year in noncoding single copy
      sequence. Within A. thaliana we found 12 substitution (single bp) and eight
      insertion/deletion (indel) polymorphisms, separating the 25 accessions into 15
      haplotypes. Eight of the A. thaliana accessions from central Sweden formed one
      cluster, which was separated from a cluster consisting of central European and
      extreme southern Swedish accessions. This latter cluster also included the A.
      suecica accessions, which were all identical except for one 5 bp indel. We
      interpret this low level of variation as a strong indication that A. suecica
      effectively has a single origin, which we dated at 20 000 years ago or more.

PMID- 14635918
TI  - Simultaneous hermaphrodites reproducing in pairs self-fertilize some of their
      eggs: an experimental test of predictions of mixed-mating and Hermaphrodite's
      Dilemma theory.
AB  - Theory predicts (1) that mixed-mating systems (i.e. reproduction through both
      selfing and outcrossing) should usually not evolve and (2) that reproducing
      simultaneous hermaphrodites should be in a conflict over the preferred sexual
      role (The Hermaphrodite's Dilemma). In an in vitro system with the endoparasitic
      cestode Schistocephalus solidus, a simultaneous hermaphrodite, we tested
      predictions of both the mixed-mating and the Hermaphrodite's Dilemma theory.
      Using microsatellite markers, we measured the proportion of selfed offspring and
      the total reproductive output of each worm within pairs varying in mean weight
      and weight difference. Worms produced more outbred offspring not only with
      increasing total weight of the pair, but also with decreasing weight difference
      between the two paired worms. These results suggest: (1) that this parasite
      species reproduces by mixed-mating, which may be maintained by stochastic density
      fluctuations in the definitive host and hence unpredictability of self
      reproduction and (2) reproductive conflict may prevent worm pairs from achieving
      an optimal intermediate selfing rate.

PMID- 14635919
TI  - Examining costs of induced and constitutive immune investment in Tenebrio
      molitor.
AB  - Central to the conceptual basis of ecological immunity is the notion that immune
      effector systems are costly to produce, run, and/or maintain. Using the mealworm
      beetle, Tenebrio molitor, as a model we investigated two aspects of the costs of
      innate immunity. We conducted an experiment designed to identify the cost of an
      induced immune response, and the cost of constitutive investment in immunity, as
      well as potential interactions. The immune traits under consideration were the
      encapsulation response and prophylactic cuticular melanization, which are
      mechanistically linked by the melanin-producing phenoloxidase cascade. If
      immunity is costly, we predicted reduced longevity and/or fecundity as a
      consequence of investment in either immune trait. We found a measurable longevity
      cost associated with producing an inducible immune response (encapsulation). In
      contrast to other studies, this cost was expressed under ad libitum feeding
      conditions. We found no measurable costs for constitutive investment in immunity
      (prophylactic investment in cuticular colour).

PMID- 14635920
TI  - Correlations between ultraviolet coloration, overwinter survival and offspring
      sex ratio in the blue tit.
AB  - We studied the correlations between offspring sex ratio, UV coloration and
      overwinter survival in a population of blue tits, breeding in Gotland, Sweden,
      over three consecutive breeding seasons. In 2 of 3 years, we found that females
      paired to males with relatively brighter UV-coloration produced a greater
      proportion of sons in their broods, and that this effect was significant with all
      3 years combined, despite a significant year by male UV interaction. In addition,
      we found other correlates of sex ratio (breeding time, female age and clutch
      size) in some, but not all years, and some of these showed significantly
      different relationships with sex ratio between years. In both years for which
      data were available, there were indications that males with relatively brighter
      UV coloration, and that paired with females that produced male-biased clutches,
      were more likely to survive to the next year. In addition, we also found that in
      both males and females, individuals produced similar sex ratios in consecutive
      years. Because correlations with the sex ratio may be expected to be weak,
      variation in results between years within the same population may be explained by
      low statistical power or genuine biological differences. Our results suggest that
      conclusions about sex ratio variation in birds should be based on multiple years.
      The correlations that we found in some years of this study are consistent with
      models of adaptive sex ratio adjustment in response to mate quality. However,
      careful experimental work is required to provide tests of the assumptions of
      these models, and should be a priority for future work.

PMID- 14635921
TI  - Sexual conflict and indirect benefits.
AB  - Recent work on sexual selection and sexual conflict has explored the influence of
      indirect effects on the evolution of female mating behaviour. It has been
      suggested that the importance of these effects has been underestimated and that
      the influence of indirect effects may actually be of relatively greater
      significance than direct effects. Additionally, it has also been suggested that
      all indirect effects, both good genes and sexy son, are qualitatively equivalent.
      Here a counterpoint to these suggestions is offered. We argue two main points:
      (1) it is unlikely that indirect effects will commonly outweigh direct effects,
      and (2) that there are important differences between good genes and sexy son
      indirect effects that must be recognized. We suggest that acknowledgement of
      these distinctions will lead to increased understanding of processes operating in
      both sexual conflict and sexual selection.

PMID- 14635922
TI  - Reproductive challenges facing the cattle industry at the beginning of the 21st
      century.
AB  - The aim of this review is to pinpoint the areas that require further research for
      greatest impact to improve the efficiency of dairy and beef production. Increased
      knowledge about the principal causes of reduced fertility is essential. Increases
      in milk yield have been at the expense of reduced fertility in dairy cows and
      although diet has a major impact, the precise interaction between nutrition and
      reproduction still needs to be characterized in both beef and dairy cows.
      Furthermore, during periods of inadequate nutrition or stress, the intensity of
      oestrus is reduced by inadequate exposure to oestradiol. However, it is still
      unclear which pheromones are involved at oestrus, how synthesis is controlled and
      how pheromones are detected in herd-mates. GnRH may be involved in behaviour but
      the brain centres that translate hormonal messages are unknown. Attempts to
      overcome poor oestrous detection include measurements of milk progesterone,
      telemetric pressure detectors and devices that record the extra activity at
      oestrus. Substitution of heat detection by 'hormone treatment remedies' has met
      strong consumer resistance in Europe. The creation of larger cattle units and
      increased movements world-wide render herds more susceptible to infectious
      agents, such as Neospora, Leptospira, Trypanosoma and Bovine Viral Diarrhoea
      virus (BVDv), but it is unclear how other clinical conditions, such as lameness
      or endometritis, also interfere with ovarian function. The future of dominant
      follicles selected within 14 days after parturition is crucial--normal ovulation,
      prolonged persistence or atresia. Calving carries the greatest risk in the
      reproductive life of a cow and yet little work has focused on reducing the
      frequency of this event. For dairy cows, a greater understanding about induced or
      extended lactation is required. For beef animals, precise induction of twinning
      and nutritional adjustments could produce two offspring per pregnancy. At the
      start of pregnancy, the trophoblast produces interferon to prevent luteolysis,
      but the immunological implications are unknown and it is not clear how the rest
      of pregnancy is maintained. Profiles of pregnancy specific protein B (PSPB) have
      increased understanding of embryonic death. However, 25% of cows in abattoirs are
      pregnant, even though 30% of involuntary cullings are 'for failing to conceive'.
      Clearly, this is an area of wastage that requires urgent resolution. It is
      unknown why undernutrition at the time of insemination or in early pregnancy
      leads to delayed births, low fetal weights and later adverse health. At the end
      of pregnancy, the fetus controls the onset of parturition, but very little is
      known about the biochemical control of cervical dilation and placental
      separation. On the male side, bulls are selected for optimal freezability of
      semen; however, there is as yet no reliable predictor for semen fertility.
      Methods for accurately pre-determining the sex of both semen and embryos will
      revolutionize the dairy and beef industries.

PMID- 14635923
TI  - Aspects of reproductive performance in small ruminants--opportunities and
      challenges.
AB  - Ovulation rate is the principal source of variation in the reproductive rate of
      small ruminants. There is extensive variability in this trait both in terms of
      major genes and polygenes. Identification of the DNA changes responsible for the
      Booroola and Inverdale effects enabled testing for these mutations in any
      population. Surprisingly, in only one of six populations, with segregation of
      major genes for ovulation rate, could the effect be attributed to one of these
      mutations. Current evidence shows that there are five distinct loci that have
      large effects on ovulation rate. Selection on ovulation rate in Finn sheep
      produced a 2.2-fold change without any evidence for major gene involvement. The
      response appears to reflect changes in the thresholds that control the number of
      ova shed, indicating that a fundamentally different mechanism is involved from
      those shown for Booroola and Inverdale genes, and probably other major genes. The
      results also indicate that the variability of ovulation rate, for a given mean
      value, can be reduced by genetic selection. This has direct implications for
      neonatal survival, which declines rapidly as the size of the litter at birth
      increases above two - a major limitation on the exploitation of the known major
      genes. The effectiveness of genetic improvement programmes, especially in sheep,
      would be greatly enhanced if the problem of poor pregnancy rate from cervical
      insemination of frozen-thawed semen was solved. Recent studies reveal major
      differences among ewe breeds and large ram-to-ram variation in pregnancy rate
      from cervical AI with frozen-thawed semen. Identification of the basis for ram-to
      ram variation could be exploited immediately in selecting rams for AI. Progress
      in this area would greatly facilitate the exploitation of molecular genetic
      information in the genetic improvement of small ruminants.

PMID- 14635924
TI  - Enhancing reproductive performance in dairy buffalo: major constraints and
      achievements.
AB  - Buffalo are of high economic importance for farmers in several developing
      countries but reproductive performance is poor. A large proportion of heifers
      attain puberty at 3-5 years of age. A good quality diet supplemented with extra
      nutrients reduces the age of puberty, whereas the effects of administration of
      exogenous GnRH or equine chorionic gonadotrophin (eCG) are equivocal. The
      incidence of anoestrus in buffalo ranges from 20 to 80% depending on season. Most
      buffalo cease ovarian cyclicity during hot summers probably due to the combined
      effects of nutrition, environment and management. Keeping buffalo cool by
      wallowing, water sprinklers or shade improves fertility. Supplementary feeding
      with Urea Molasses Multi-nutrient Blocks (UMMB) for 60 days before calving
      enhances the early onset of postpartum oestrus. Regular UMMB supplementation also
      improves pregnancy rates in anoestrous non-pregnant buffalo. Prepartum vaginal
      prolapse is hereditary and eradication can be achieved by genetic selective
      breeding programmes. Treatment with calcium, phosphorus and progesterone gives
      only transient relief to clinical cases. Uterine torsion is the most common cause
      of dystocia (70%). Deployment of Sharma's detorsion method and anti-stress
      measures increase survival rates in cases presented within 36 h. In conclusion,
      greater understanding about the effects of better year-round nutrition, improved
      management and markers for logical breeding programmes are essential to curtail
      the incidence of the reproductive disorders that reduce buffalo fertility.

PMID- 14635925
TI  - The main challenges facing camel reproduction research in the 21st century.
AB  - The reproductive efficiency of camels under their natural pastoral conditions is
      low. The reasons for this low reproductive efficiency include the short breeding
      season, the late age of reaching puberty and the long gestation period of 13
      months. The introduction of controlled breeding programmes is important but
      several problems have to be considered. For example, oestrous behaviour is very
      vague and difficult to interpret, as it does not often relate to follicular
      development in the ovaries. In addition, all camelids are induced ovulators that
      normally ovulate only in response to mating, so alternative methods of inducing
      ovulation, such as injecting gonadotrophic hormones, have been investigated. The
      use of embryo transfer is becoming increasingly important but involves the
      necessity to superovulate the donors and synchronize the recipients so that they
      ovulate preferably 24 h after the donor. Superovulation can be achieved using
      exogenous gonadotrophins, although there is a high incidence of follicle
      luteinization before mating, of overstimulated ovaries and non-responsive
      females. The development of AI in camels is complicated by the difficulty of
      collecting semen and the gelatinous nature of the semen produced. However,
      diluting semen in Green Buffer and inseminating a minimum of 300 x 10(6) live
      spermatozoa has given encouraging results. The ability to control the follicular
      cycle of camels is leading to an improvement in reproductive efficiency.

PMID- 14635926
TI  - Oocyte-somatic cell communication.
AB  - The physical interface between the female germ line and enveloping somatic cells
      is dynamically modified throughout the course of folliculogenesis. How selective
      pathways for communication between the oocyte and granulosa cell are established
      and regulated remains to be determined, but insights into the structural basis
      for this communication are emerging. This review summarizes the available
      evidence that supports the notion that the integration of oogenesis with
      folliculogenesis is achieved by regulated cell interactions between oocytes and
      granulosa cells.

PMID- 14635927
TI  - Evaluation of members of the TGFbeta superfamily as candidates for the oocyte
      factors that control mouse cumulus expansion and steroidogenesis.
AB  - Oocytes secrete factors that control cumulus and granulosa functions, including
      cumulus expansion and steroid hormone production. Some members of the
      transforming growth factor beta (TGFbeta) superfamily influence these activities,
      yet it is still not determined conclusively whether any of these superfamily
      members are the previously reported oocyte-secreted factors. The aim of this
      study was to examine the effects of TGFbeta1 and growth differentiation factor 9
      (GDF-9) on cumulus expansion and progesterone production by mouse oocytectomized
      (OOX) complexes in culture. TGFbeta1 mimics the effects of oocytes by both
      enabling cumulus expansion and inhibiting progesterone production; however,
      neutralizing antibodies to TGFbeta1 in cultures of cumulus-oocyte complexes
      (COCs) or in co-cultures of OOX complexes failed to inhibit the ability of
      oocytes to enable cumulus expansion or inhibit progesterone production. Activin A
      had no effect on progesterone production by OOX complexes. In experiments using
      oocytes obtained from mice with deficient expression of GDF-9, OOX complexes
      cultured in the presence of heterozygous oocytes were capable of full expansion,
      whereas OOX complexes cultured with oocytes from GDF-9 null mice did not expand.
      Similarly, GDF-9 null oocytes failed to suppress FSH-induced progesterone
      production by OOX complexes. These results support the hypothesis that GDF-9 is
      the cumulus expansion enabling factor produced by mouse oocytes and that GDF-9
      also inhibits cumulus progesterone production; however, the possibility remains
      that loss of GDF-9 may indirectly affect the ability of oocytes to produce the
      factors that regulate cumulus cell activity.

PMID- 14635928
TI  - Mechanisms regulating follicular development and selection of the dominant
      follicle.
AB  - Reproductive function is an integrated process encompassing both extra-ovarian
      signals, such as gonadotrophins, and intrafollicular factors, such as locally
      produced growth factors. Initiation of primordial follicle growth and the early
      stages of folliculogenesis can occur without gonadotrophins. However, in vivo and
      in vitro studies indicate that FSH may stimulate the rate of preantral follicle
      growth and that it can take only 3 months for a primordial follicle to reach the
      ovulatory stage. Antral follicle development from 2 and 4 mm in diameter in sheep
      and cattle, respectively, is gonadotrophin dependent. During the oestrous cycle a
      transient increase in circulating FSH precedes the recruitment of a group of
      follicles. Recruited follicles are characterized by induction of expression of
      mRNAs encoding a range of steroidogenic enzymes, gonadotrophin receptors and
      local regulatory factors. As follicles continue to mature, there is a transfer of
      dependency from FSH to LH, which may be part of the mechanism involved in
      selection of follicles for continued growth. The mechanism of selection of the
      ovulatory follicle seems to be linked to the timing of mRNA expression encoding
      LHr and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in granulosa cells.
      Locally produced growth factors, such as the insulin-like growth factors (IGFs)
      and members of the transforming growth factor beta (TGFbeta) superfamily
      (inhibins, activins and bone morphogenetic proteins (BMPs)), work in concert with
      gonadotrophins throughout the follicular growth continuum. The roles of growth
      factors in follicular development and survival are dependent on gonadotrophin
      status and differentiation state, including morphology. In conclusion, it is the
      integration of extraovarian signals and intrafollicular factors that determine
      whether a follicle will continue to develop or be diverted into atretic pathways,
      as is the case for most of the follicles in monovulatory species, such as cattle.

PMID- 14635929
TI  - Germ cell-somatic cell interactions during spermatogenesis.
AB  - The adult testis has two essential functions, namely the synthesis and secretion
      of the steroid hormone testosterone and the production of mature spermatozoa.
      Germ cells undergo mitosis, meiosis and condensation (spermiation) in close
      association with Sertoli cells and in defined associations with each other within
      the seminiferous epithelium. Normal spermatogenesis and fertility are dependent
      upon paracrine interactions between the somatic cells (Sertoli, Leydig and
      peritubular) and the germ cells, and upon endocrine support from the pituitary
      gland. Evidence for paracrine interactions between somatic and germ cells has
      been gained from observations on the patterns of expression of proteins, studies
      on isolated cell populations, germ cell or Leydig cell ablation with toxicants,
      mouse mutants and transgenics, and more recently from germ cell transplantation.

PMID- 14635930
TI  - Morphological assessment of preimplantation embryo quality in cattle.
AB  - The extensive use of embryo technologies has emphasized the need for assessing
      embryo quality by morphological techniques, such as transmission electron
      microscopy, immunocytochemistry for confocal laser scanning microscopy and
      fluorescence in situ hybridization. By a combination of these techniques, it has
      been possible to demonstrate: (i) that rRNA gene activation, as monitored by
      embryonic nucleolar development, is comparable in bovine embryos developed in
      vivo and produced in vitro, whereas reconstructed nuclear transfer embryos may be
      deviant, (ii) that generating embryos by both in vitro production and
      reconstruction by nuclear transfer is associated with increased occurrence of
      apoptosis, in particular in the inner cell mass of blastocysts, and (iii) that
      these two embryo production techniques are associated with increased occurrence
      of mixoploidy that is, embryos presenting a large population of normal diploid
      cells and a small population of abnormal haploid or polyploid cells. It is clear
      that blastocysts that appear healthy at stereomicroscopy may have subcellular
      defects. Therefore, the possibility of long-term evaluation in vitro of embryos
      after hatching has been examined. However, whereas embryos developing in vivo
      after hatching present a number of well defined developmental milestones, such as
      elongation of the trophoblast, formation of hypoblast and epiblast followed by
      differentiation of endoderm, mesoderm and ectoderm, in vitro culture systems for
      development beyond the blastocyst stage currently allow the embryo to complete
      only a single milestone, namely hypoblast formation.

PMID- 14635931
TI  - The use of genomics and proteomics to understand oocyte and early embryo
      functions in farm animals.
AB  - Oocyte maturation, a simple and visible phenomenon, is about to be transformed
      into a complex and not so visible molecular cascade leading to the marking of the
      following generation. The study of oocyte maturation in mammals is progressively
      changing towards a more molecular approach. This review addresses the main
      challenges in the study of RNA extraction and quantification in oocytes and
      embryos as well as the importance of the mRNA maturation. The identification of
      specific genes in oocytes and embryos is now possible with the use of powerful
      tools, such as library analysis or subtractions, DNA array, comparative analysis
      of databanks from other mammals or animals and two-dimensional gel
      electrophoresis analysis. Finally, RNA interference is a useful tool for studying
      gene function by knocking out the activity of specific genes and will be used in
      oocytes and embryos.

PMID- 14635932
TI  - Cloning in livestock agriculture.

PMID- 14635933
TI  - Gene expression in the developing embryo and fetus.
AB  - Determining the stage- and tissue-specific patterns of gene expression shown by
      the embryo and fetus will provide information about the control of normal
      development. Identification of alterations in these patterns associated with
      specific abnormal phenotypes will also be informative regarding the underlying
      molecular mechanisms. In addition, qualitative and quantitative changes in gene
      expression that deviate from the norm may provide a potential marker system for
      predicting future developmental defects, a system that would be particularly
      useful in preimplantation embryo technologies before recipient transfer. However,
      there are a number of important issues regarding the interpretation and relevance
      of many gene expression studies currently undertaken that are often not
      considered or are ignored. Even when rigorous methodology is applied to detect
      differences in gene expression, their functional significance is rarely defined.
      This review discusses the relevance of gene expression changes as diagnostic
      markers in relation to protein and epigenetic changes and indicates that gene
      expression studies should be rigorously designed and interpreted to yield
      meaningful results.

PMID- 14635934
TI  - Consequences of manipulating gametes and embryos of ruminant species.
AB  - During the past 12 years, ruminants have provided a focus for some significant
      advances in mammalian reproductive biotechnologies. Lambs were the first
      offspring generated after nuclear transfer of fetal or adult cells to enucleated
      oocytes, and many calves of pre-determined gender are today the result of
      commercialized semen sexing. In 1990, the birth of one calf provided living proof
      that even 'dead' spermatozoa can be paternal, whereas, more recently, a short
      lived gaur calf and viable mouflon lamb represented a novel option for
      conservation of endangered species. As well as highlights, hazards have emerged,
      resulting in setbacks or developmental anomalies, such as those associated with
      the large offspring syndrome which encompasses a range of adverse fetal,
      placental and post-natal phenomena expressed in ruminants. In this review, the
      developmental and other consequences of applying manipulative procedures, such as
      assisted fertilization, semen sexing, cloning and gene transfer, to gametes and
      embryos from bovine, ovine and caprine species are considered. Although assisted
      fertilization techniques can overcome mammalian infertility, they also usurp
      natural gamete selection safeguards, but not always with impunity. In the case of
      manipulations such as cloning, and to a lesser extent gene transfer, it is
      evident that nuclear-cytoplasmic interactions and nuclear-mitochondrial DNA
      interdependences are at least partially damaged or destroyed with a view to
      reconstruction. Therefore, among surviving zygotes and embryos it is inevitable
      that the legacy is frequently one of altered genetic, epigenetic or cellular
      programmes and processes.

PMID- 14635935
TI  - Ruminant models of prenatal growth restriction.
AB  - Intrauterine growth restriction (IUGR) is a significant health issue that not
      only affects infant mortality and morbidity, but may also predispose individuals
      to coronary heart disease, diabetes, hypertension and stroke as adults. The
      majority of IUGR pregnancies in humans are characterized by asymmetric fetal
      growth, resulting from inadequate nutrient transfer to the fetus. Furthermore,
      most of these pregnancies involve functional placental insufficiency, and may
      also show altered umbilical velocimetry. As the severity of IUGR increases, the
      fetus becomes increasingly hypoxic, hypoglycaemic and acidotic. In addition,
      placental transfer or utilization of some amino acids is known to be altered in
      IUGR pregnancies. Although a great deal has been learned from clinical studies of
      human IUGR, appropriate animal models are required to define completely the
      mechanisms involved in the development of IUGR. The pregnant sheep is a long
      standing model for placental-fetal interactions, and fetal growth restriction can
      be induced in pregnant sheep by maternal nutrient restriction, maternal nutrient
      excess, administration of glucocorticoid, utero-placental embolization,
      carunclectomy and maternal hyperthermia. Although all of these sheep models are
      capable of inducing fetal growth restriction, the degree of restriction is
      variable. This review compares these sheep models of IUGR with the
      characteristics of human IUGR.

PMID- 14635936
TI  - Consequences of intra-uterine growth retardation for postnatal growth, metabolism
      and pathophysiology.
AB  - Intra-uterine growth retardation (IUGR), caused by maternal undernutrition or
      placental insufficiency, is usually associated with disproportionately large
      reductions in the growth of some fetal organs and tissues (thymus, liver, spleen,
      thyroid) and impaired cellular development of other tissues (small intestine,
      secondary wool follicles, skeletal muscle). Growth of other tissues, most notably
      brain, is relatively unimpaired. In our restudy of postnatal consequences of IUGR
      in the offspring of prolific ewes, growth-retarded newborn lambs tended to be
      hypoglycaemic and showed sluggish postnatal engagement of the growth hormone (GH)
      insulin-like growth factor (IGF) system. When artificially reared in an optimum
      environment, low birth weight lambs grew at rates similar to those of normal
      lambs. However, low birth weight lambs were fatter at any given weight,
      apparently related to their high energy intakes, especially soon after birth, had
      low maintenance energy requirements, and limited capacity for bone and muscle
      growth. These growth characteristics were accompanied by higher plasma
      concentrations of GH and leptin, and lower concentrations of insulin-like growth
      factor I (IGF-I) during the first 2 weeks of postnatal life, and higher
      concentrations of insulin during subsequent growth up to 20 kg body weight.
      Emerging evidence indicates that in sheep, as in rodents, fetal programming of
      postnatal cardiovascular and metabolic dysfunctions is associated with IUGR and
      may be mediated partly by overexposure of the fetus to cortisol. Similar
      postnatal responses can be elicited by maternal undernutrition or cortisol
      treatment in early to mid-pregnancy without changing the growth of the fetus or
      placenta.

PMID- 14635937
TI  - Lives in the balance: responsiveness of the corpus luteum to uterine and
      embryonic signals.
AB  - This review focuses on factors that may affect the sensitivity of the corpus
      luteum to uterine prostaglandin F2alpha (PGF2alpha) and embryonic signals. The
      heterogeneity of the types of cell that are present within the corpus luteum
      results in complex interactions that ensure complete luteal regression in
      response to PGF2alpha. There is not likely to be a single factor that determines
      responsiveness. The sensitivity of the corpus luteum depends on the proper
      balance of a variety of factors that are involved in mediating the effects of
      PGF2alpha. This balance is achieved as the early corpus luteum undergoes
      development, but may also be altered by embryonic factors to rescue the corpus
      luteum during early pregnancy.

PMID- 14635938
TI  - Follicle growth, corpus luteum function and their effects on embryo development
      in postpartum dairy cows.
AB  - Absent or irregular ovarian cycles in lactating dairy cows are caused by failure
      to ovulate the dominant follicle at the appropriate time. The follicle then
      either regresses or develops into a cyst. This process can be triggered by a
      variety of metabolic and disease factors that act at the hypothalamus and
      pituitary gland to inhibit pulsatile LH secretion and the LH surge, and at the
      ovary to reduce follicular growth and oestradiol production. Cows of poor energy
      status have low circulating concentrations of insulin-like growth factor I (IGF
      I). Predisposing factors include calving difficulties, inappropriate diet,
      reduced intake of dry matter and a high rate of body condition score loss.
      Various stressors predispose the follicle to cyst development by inhibiting the
      LH surge and ovulation; these include common infections, such as mastitis. Even
      when ovulation does occur, poor follicular development may result in production
      of an inadequate corpus luteum. The timing of the increase in progesterone in the
      early luteal phase (days 4-5) appears to be a key determinant of fertility,
      probably because it alters the secretory activity of the reproductive tract, thus
      influencing embryonic growth and interferon-tau production. A period of negative
      energy balance after calving can reduce fertility even though metabolic
      parameters have apparently improved at the time of service.

PMID- 14635939
TI  - Evolution of the interferon tau genes and their promoters, and maternal
      trophoblast interactions in control of their expression.
AB  - It is well established that the interferon tau (IFN-tau) family of proteins play
      a major role in preventing the regression of the corpus luteum during early
      pregnancy in ruminants, such as cattle, sheep and goats, but not in other
      mammals. These interferons, which are structurally and functionally related to
      type I interferon, such as IFN-alpha and -omega, arose from a duplication of an
      IFN-omega gene approximately 36 million years ago. The IFN-tau genes have
      continued to duplicate since that time and have acquired the ability to be
      transcribed uniquely in the trophectoderm. Low expression is first detectable at
      the blastocyst stage, but massive transcriptional upregulation occurs a few days
      later during the initial stages of conceptus elongation. Expression is finally
      terminated upon trophectoderm attachment to uterine endometrium. The major
      promoter element that controls expression is an Ets-2/AP-1 enhancer element.
      Growth factors and cytokines released by the maternal endometrium that, possibly
      in response to progesterone, act through Ras and the mitogen-activated protein
      kinase (MAP-kinase) signal transduction pathway have been implicated in
      controlling IFN-tau gene transcription by activating Ets-2. This timely
      expression of IFN-tau is not only required to rescue the corpus luteum of
      pregnancy but may also be an indicator of conceptus fitness, thereby serving as a
      critical factor that dictates the continuation of pregnancy in ruminants.

PMID- 14635941
TI  - Stress and the control of LH secretion in the ewe.
AB  - Stress influences the activity of the reproductive system at several sites. One
      of the most significant effects is at level of the GnRH secretory system to
      reduce GnRH pulsatility and thus LH pulsatility. This in turn reduces the
      oestradiol signal that stimulates the GnRH-LH surge in the follicular phase.
      Three sequential phases have been identified in the induction of the GnRH-LH
      surge by oestradiol: (i) activation, (ii) transmission and (iii) surge secretion.
      There is evidence that administration of endotoxin prevents activation but not
      transmission, hypoglycaemia blocks both activation and transmission, whereas
      truck transport is effective during the late, but not early, transmission phase.
      Opioids mediate the suppressive effects of hypoglycaemia on both LH pulsatility
      and the delayed onset of the LH surge in ewes. The exact neurocircuitry used in
      sheep is yet to be identified but many of the connections that are proposed as
      important in rats are present in sheep. Corticotrophin-releasing hormone (CRH)
      neurones in the paraventricular nucleus that project axons to the median eminence
      probably do not directly inhibit GnRH, but either afferent or parallel central
      pathways are involved. New members of the CRH peptide and receptor families have
      been identified, but roles in the control of reproduction have yet to be
      determined.

PMID- 14635940
TI  - Regulation of embryo survival in cattle.
AB  - Evidence is presented that bovine somatotrophin (bST) treatment of lactating
      dairy cows enhances both expression of oviductal insulin-like growth factor II
      (IGF-II) mRNA and endometrial insulin-like growth factor binding protein 3 (IGFBP
      3) mRNA between day 3 and day 7 of the oestrous cycle. mRNA encoding growth
      hormone (GH) receptor in endometrial tissues increased between day 3 and day 7 of
      the oestrous cycle. The changes induced by bST treatment may contribute to
      stimulation of embryo development and increase pregnancy rates in lactating dairy
      cows. Additive effects of bST and rb interferon tau (rbIFN-tau) to inhibit
      phorbol ester induction of prostaglandin F2alpha secretion in immortalized bovine
      endometrial cells indicates that there is interplay between their signal
      transduction pathways. Non-lactating dairy cows were killed at day 17 after
      oestrus to evaluate the effects of pregnancy status (cyclic versus pregnant) and
      bST (bST versus control) treatment on endometrial gene expression. Distinctly
      different mRNA and protein responses were detected between cyclic and pregnant
      cows that were related to luteolytic-antiluteolytic drive (that is expression of
      progesterone receptor, oxytocin receptor, oestradiol receptor alpha and
      prostaglandin GH synthase 2 (PGHS-2)). The bST-induced changes in PGHS-2 protein
      (+), oxytocin receptor mRNA (+) and oestrogen receptor alpha protein (+) may
      potentially affect the mechanisms associated with maintenance of pregnancy. Two
      experiments were conducted to evaluate whether ovarian follicular suppression
      induced by biodegradable deslorelin implants would reduce either early or late
      embryo losses. A 450 microg deslorelin implant used to induce ovulation in a
      timed insemination programme decreased subsequent follicular development and
      tended to reduce early embryo losses, whereas a 2.1 mg deslorelin implant failed
      to reduce late embryonic losses when inserted on day 27 of pregnancy.

PMID- 14635942
TI  - Leptin actions on the reproductive neuroendocrine axis in sheep.
AB  - There is a growing literature on the role of leptin in appetite and
      neuroendocrine regulation in domestic ruminants. Circulating leptin concentration
      is higher in fat than in thin sheep, is reduced by chronic underfeeding and is
      higher in sheep subjected to long-day rather than short-day photoperiods. Leptin
      is reduced acutely by fasting and increases after meals so that there are long-
      and short-term components to the systemic leptin signal. Nutritional stimulation
      of reproductive neuroendocrine output is associated with increased circulating
      concentrations of leptin; peripheral leptin administration restores LH secretion
      in fasted sheep, and leptin is permissive (although not a trigger) for puberty.
      Intracerebroventricular (i.c.v.) pharmacological leptin infusion stimulates LH in
      underfed but not in well-fed sheep, and reduces food intake in well-fed sheep. A
      single i.c.v. pharmacological injection or physiological infusion of leptin
      stimulates LH in well-fed sheep, with or without a concomitant decrease in
      appetite. Furthermore, these appetite and LH responses are differentially
      affected by photoperiod, indicating that different neuronal pathways may mediate
      the two responses. Hypothalamic leptin receptors co-localize with orexigenic and
      anorexigenic neurones, some of which contact GnRH cells, but the confluence of
      leptin signalling with photoperiod (melatonin) signalling remains unresolved.
      Photoperiod-entrained sheep provide potential models of altered central leptin
      sensitivity, in which downstream mechanisms regulating appetite and GnRH may be
      dissociated.

PMID- 14635943
TI  - Sexually differentiated regulation of gnRH release by gonadal steroid hormones in
      sheep.
AB  - Exposure of the sheep fetus to testosterone from day 30 to day 90 of a 147 day
      gestation causes the neurones that control GnRH secretion, the GnRH neuronal
      network, to become organized in a sex-specific manner. After androgen exposure in
      utero, GnRH neurones are activated in a sexually differentiated pattern by
      gonadal steroid hormones. Specifically, follicular phase concentrations of
      oestrogen trigger a GnRH 'surge' in ewes, but not in rams or females treated with
      androgen during fetal life. Furthermore, progesterone is a less potent inhibitor
      of GnRH release in rams or females treated with androgen during fetal life. The
      reasons for the sexual differentiation of these steroid feedback mechanisms
      probably reside in a dimorphism in steroid-sensitive neural inputs to GnRH
      neurones. The density of neurones containing oestrogen receptor alpha is sexually
      differentiated in areas of the ovine brain that are known to be involved in the
      steroidal regulation of GnRH. Furthermore, neurones in these regions are
      activated in a gender-specific pattern. A determination of the neural phenotype
      of these steroid-sensitive cells will form a basis for understanding the
      mechanisms by which the GnRH neuronal network is organized and activated in a
      sexually differentiated manner.

PMID- 14635944
TI  - Origin of cerebrospinal fluid melatonin and possible function in the integration
      of photoperiod.
AB  - Melatonin, which is synthesized at night by the pineal gland, is present in the
      cerebrospinal fluid (CSF), but its entry site and its role in this compartment
      are not known. Using several approaches, we tested the hypothesis that melatonin
      enters the CSF through the pineal recess, an evagination of the third ventricle.
      CSF melatonin concentrations are higher near the pineal gland than in the
      anterior part of the third ventricle, and decrease markedly (80%) after sealing
      off the pineal recess. Moreover, ultrastructure and permeability analyses of the
      pineal-CSF interface showed that melatonin could reach the CSF either via
      delivery in situ by protruding pinealocytes that make direct contact with the CSF
      or via extracellular secretion and interstitial fluid draining into the
      ventricular lumen. These data indicate that melatonin in the CSF probably
      originates from a few pinealocytes of the basal part of the pineal gland
      neighbouring the pineal recess. Melatonin carried to the brain by the blood
      appears to be able to mediate the effects of photoperiod on reproduction, but it
      is unclear whether melatonin in CSF may fine-tune this response both in terms of
      timing and amplitude. It is critical to determine which pathway, blood or CSF,
      allows melatonin to reach its central targets more efficiently.

PMID- 14635945
TI  - The role of bone morphogenetic proteins in ovarian function.
AB  - Bone morphogenetic proteins (BMPs) represent the largest subclass of growth
      factors in the transforming growth factor beta (TGF-beta) superfamily. BMPs have
      proven to be multifunctional regulators of a wide variety of biological processes
      in numerous types of cell and tissue. The role of inhibins, activins and TGF
      betas (which also belong to the TGF-beta superfamily) in reproduction has been
      studied extensively over the last 15 years. However, there were no reports on the
      role of BMPs in the mammalian ovary until 1999 when we reported an intrinsic
      ovarian BMP system replete with BMP ligands, receptors and novel biological
      functions. Since this report it has become clear that the BMP system plays an
      important role in the regulation of ovarian function, evidenced by the ability of
      BMPs to control granulosa cell proliferation and cytodifferentiation, as well as
      oocyte development. The physiological relevance of the BMP system has recently
      been highlighted by the discovery that genetic mutations in the BMP-15 ligand or
      the BMP type IB receptor lead to critical aberrations in folliculogenesis and
      ovulation. This review provides a current overview of the rapidly emerging field
      of the BMP system in mammalian ovarian function.

PMID- 14635946
TI  - Oocyte-derived growth factors and ovulation rate in sheep.
AB  - The physiological mechanisms controlling ovulation rate in mammals involve a
      complex exchange of endocrine signals between the pituitary gland and the ovary,
      and a localized exchange of intraovarian hormones between the oocyte and its
      adjacent somatic cells. The discoveries in sheep of mutations in bone
      morphogenetic protein 15 (BMP15) and bone morphogenetic protein receptor type IB
      (BMPR-IB) together with recent findings on the physiological effects of growth
      differentiation factor 9 (GDF9) and BMP15 on follicular development and ovulation
      rate highlight some important differences in the way in which the oocyte may
      function in mammals with different ovulation rate phenotypes. In sheep, BMP15 and
      GDF9 have each been shown to be essential for the early and later stages of
      follicular development. In addition, ovulation rate is sensitive to changes in
      the dose of either of these two oocyte-derived growth factors. These findings are
      in contrast to those reported for mice in which GDF9, but not BMP15, is essential
      for follicular development. The evidence to date is consistent with the
      hypothesis that the oocyte plays a central role in regulating key events in the
      process of follicular development and hence, is important in determining
      ovulation rate. Moreover, it appears that the mechanisms that the oocyte uses to
      control these processes differ between species with low and high ovulation rate
      phenotypes.

PMID- 14635947
TI  - Prolificacy genes in sheep: the French genetic programmes.
AB  - It has been demonstrated that variations in litter size or ovulation rate in
      different breeds of sheep can be associated with the segregation of several major
      genes. This set of natural mutants constitutes a valuable resource to determine
      key points in the biochemical pathways controlling the development of ovarian
      follicles. The French genetic programmes were devised to identify two of these
      genes: the Booroola (FecB) and Lacaune genes. The FecB prolific mutation
      corresponds to a non-conservative mutation (Q249R) in the intracellular kinase
      signalling domain of the bone morphogenetic protein receptor type IB (BMPR-IB)
      gene. The Lacaune gene is situated on ovine chromosome 11. Positional cloning is
      currently in progress to identify the relevant gene and mutation. A similar
      approach, limited to linkage testing of candidate genes, is proposed to classify
      the different prolificacy genes in sheep.

PMID- 14635948
TI  - Bone morphogenetic proteins and folliculogenesis: lessons from the Booroola
      mutation.
AB  - The Booroola phenotype is associated with a point mutation in the kinase domain
      of the bone morphogenetic protein receptor 1 B (BMPR1 B), and is characterized by
      'precocious' differentiation of ovarian follicles, leading to the production of
      large numbers of ovulatory follicles that are smaller in diameter than wild-type
      follicles. These smaller follicles attain differentiation markers, such as
      expression of mRNA for P450 aromatase and inhibin-betaA subunit, granulosa cell
      LH receptors and aromatase activity, earlier than follicles from wild-type ewes.
      However, the preovulatory follicles from mutant ewes collectively secrete similar
      quantities of oestradiol, androstenedione and inhibin A in exactly the same
      pattern as wild-type ewes, which result in similar concentrations of FSH. The
      available evidence strongly indicates that the Booroola mutation exerts its
      action at the ovary rather than by altering gonadotrophin secretion. The bone
      morphogenetic protein (BMP) receptors and putative ligands are ubiquitously
      expressed within the ovary and BMPs seem to be involved in the paracrine
      regulation of FSH action. Thus, if the mutation is causing a reduction in BMPR1 B
      signalling, it may act on an inhibitor of follicle differentiation. Further
      research in this area will concentrate on the elucidation of the natural ligands
      for BMPR1 B at different stages of follicle development and examine the effect of
      BMPR1 B mutation on the downstream signalling cascade.

PMID- 14635949
TI  - Regulation of nutrient uptake and metabolism in pre-elongation ruminant embryos.
AB  - Our current understanding of pre-elongation embryo metabolism and its regulation
      by factors both intrinsic to the embryo and present in its immediate environment
      is limited mainly to studies in rodents and of ruminant embryos that have been
      cultured in vitro. Energy metabolism in such embryos is initially low and
      dependent on oxidative phosphorylation for the generation of ATP. The embryo
      exhibits substrate preference for carboxylic acids, such as pyruvate, during this
      period. Glucose uptake is limited initially but increases after compaction, and
      it is metabolized mostly to lactate. Glucose uptake is facilitated by a number of
      transporters, but the presence and function of these, and their regulation by
      growth factors, such as insulin, are not well characterized. Even less is known
      about the metabolic fate of amino acids and lipids. Approximately 50% of the
      lipid fraction in the mature oocyte is in the form of triglyceride, much of which
      is oxidized during fertilization and the early cleavage stages. Immunoreactivity
      of the growth hormone receptor is detectable from day 3 after fertilization, and
      so growth hormone acting in either a paracrine or endocrine manner may serve to
      regulate glucose, glycogen and lipid metabolism. The metabolic and mitogenic
      actions of insulin and insulin-like growth factor (IGF) I and II are thought to
      be mediated mainly by the IGF-I receptor. The actions of leptin in the ruminant
      embryo are less well understood. Circulating concentrations of these growth
      factors, together with nutrients supplied to the follicle and oviduct, can be
      modified by diet, but in ways that are not fully understood. The present review
      discusses these issues and highlights areas for future research endeavour where
      emphasis is directed on to combining thoughtfully designed whole animal studies
      with in vitro culture experiments.

PMID- 14635950
TI  - Fertility in male sheep: modulators of the acute effects of nutrition on the
      reproductive axis of male sheep.
AB  - Animals adjust the time of year that they reproduce through their ability to
      perceive and respond to critical aspects of their environment, such as
      photoperiod, nutrition or the socio-sexual milieu, and their genotype determines
      the degree of response to each stimulus. Ultimately, information from
      environmental cues filters through to the GnRH neurones in the brain which are
      the primary regulator of fertility. Each of these cues has been studied in
      isolation and the mechanisms by which they affect GnRH secretion are now better,
      if not fully, understood. In the field, the brain centres that control GnRH must
      integrate information from all cues at any given time before 'formulating a
      reproductive decision'. In this review, the effect of this integration is
      illustrated by showing how the acute GnRH response to a nutritional signal can be
      modulated by genotype, photoperiod and social cues, to the point of being
      completely blocked under some circumstances. Candidate pathways that may mediate
      these modulatory effects at both the whole body and brain have been proposed,
      although none of these pathways are confirmed and some have not yet been studied.
      As a guide for further research, we propose a working model that integrates the
      inputs and explains the interactions between them.

PMID- 14635951
TI  - Interactions between nutrition and ovarian activity in cattle: physiological,
      cellular and molecular mechanisms.
AB  - The effects of acute changes in dietary intake on ovarian activity can be
      correlated with changes in circulating concentrations of metabolic hormones
      including insulin, insulin-like growth factor I (IGF-I), growth hormone and
      leptin. There is no corresponding change in circulating gonadotrophin
      concentrations and it is proposed that the dietary induced changes in ovarian
      activity, resulting from acute changes in dietary intake, are a result of direct
      actions of these metabolic hormones on the ovary. Changes in the peripheral
      concentrations of insulin, IGF-I and leptin were also associated with the
      initiation of a synchronized wave of follicle growth and it is hypothesized that
      oestrogen secreted by the developing follicle is involved in regulating the
      secretion of these metabolic hormones. At the cellular level, physiological
      concentrations of insulin and IGF-I interact to stimulate oestradiol production
      by granulosa cells. In contrast, leptin inhibits FSH-stimulated oestradiol
      production by granulosa cells and LH-stimulated androstenedione production by
      theca cells. At the molecular level, dietary energy intake affects the expression
      of mRNA encoding components of the ovarian IGF system and these changes can
      directly influence the bioavailability of intrafollicular IGF. This, in turn, can
      increase the sensitivity or response of follicles to FSH and is one mechanism
      through which nutrition can directly affect follicle recruitment. Dietary induced
      increases in intrafollicular IGF bioavailability also have a negative effect on
      oocyte quality, and diets that are optimal for follicle growth may not
      necessarily be optimal for oocyte maturation.

PMID- 14635952
TI  - Mechanisms linking nutrition and reproduction in postpartum cows.
AB  - The reproductive physiology of postpartum cows is different from that of heifers
      because of the combined effects of the past pregnancy and lactation. Neither
      lactation nor pregnancy has a major effect on postpartum fertility when calving
      is free from disease and lactation is moderate. Postpartum beef cows in good body
      condition have conception rates nearly equivalent to those of virgin heifers once
      their uteri are involuted and they initiate ovarian cycles. However, cows will
      experience infertility when nutrient requirements for maintenance and lactation
      exceed nutrient intake (postpartum beef cows) or when nutrients are specifically
      partitioned toward lactation (postpartum dairy cows). The subsequent loss of body
      fat that occurs in either case has effects on a variety of reproductive processes
      and reproduction becomes less efficient. The mechanisms that lead to abnormal
      reproduction in nutritionally compromised postpartum cattle have been
      investigated intensively. Much of the effort has focused on the nature of the
      signal (endocrine or otherwise) that controls pituitary secretion of LH and FSH,
      the response of the ovary to LH and FSH, and other ovarian effects that are
      independent of gonadotrophins. Reproductive studies in ruminants have tended
      toward studies of follicular development and this focus relates back to solving
      the problem of anoestrus. Less work has been done on the effects of nutrition on
      the early embryo, the health of which may be predetermined by factors affecting
      the oocyte within the preovulatory follicle. Few studies have examined the effect
      of nutrition on uterine function in postpartum cattle. Solutions to postpartum
      reproduction will probably arise from a variety of approaches that include
      traditional physiology as well as more modern genomic and proteomic technologies.

PMID- 14635953
TI  - Domestic ruminants as models for the elucidation of the mechanisms controlling
      ovarian follicle development in humans.
AB  - It is necessary to understand the basic physiology underlying the complex process
      of folliculogenesis to address common causes of infertility and to devise
      innovative strategies to increase the efficiency of assisted reproduction
      technologies. Availability of suitable ovarian tissue is a major constraint to
      research in this area in humans, and monovulatory domestic ruminants represent a
      physiologically relevant model to elucidate basic mechanisms before more focused
      clinical investigations. This paper reviews the development of several whole
      animal and cell culture models in ruminants that have allowed basic
      investigations into the endocrine and local mechanisms regulating preantral and
      antral follicle development in monovulatory species. Studies on preantral
      follicle development using the ovarian autograft model have shown, contrary to
      accepted dogma, that FSH may mediate the rate at which preantral follicles grow
      and have provided evidence to support the existence of local regulatory feedback
      mechanisms that influence the rate of primordial follicle initiation and
      preantral follicle development. Studies on the endocrine control of antral
      follicle development using the GnRH-antagonist model have shown that a pulsatile
      mode of LH delivery is not a requirement for normal patterns of follicle
      development and ovarian hormone secretion. Studies on the local control of
      somatic cell differentiation using physiological cell culture models have
      highlighted the essential relationship between somatic cell communication and
      expression of differentiative markers. We conclude that the domestic ruminant
      represents a valuable model system for the elucidation of the endocrine and local
      mechanisms controlling both early and terminal stages of follicle development in
      monovulatory species. The results of these investigations have direct strategic
      relevance within clinical medicine.

PMID- 14635954
TI  - Growth and maturation of oocytes in vitro.
AB  - The development of technologies to grow and mature oocytes from the most abundant
      primordial follicles holds many attractions for clinical practice, animal
      production technology and research. However, despite much research attention, it
      has proved difficult to grow follicles from early stages to maturity in vitro, as
      relatively little is known about the biology of oogenesis. It is clear that
      throughout oocyte development in vivo, follicle cell support is fundamental to
      provide the germ cell with nutrients and growth regulators to ensure progression
      through the protracted growth phase. Conversely, the oocyte actively promotes
      growth and differentiation of the follicular cells. Both of these characteristics
      must be mimicked in vitro. Replication of the normal follicular growth span from
      the primordial to Graafian follicle stages and the changes in the trophic
      requirements of the cells, cellular interactions, morphogenesis and the sheer
      increase in bulk as the antrum forms present major challenges for follicle
      culture technology. These observations could explain why methods that have proved
      successful for the culture of isolated rodent follicles are unable to support the
      growth of larger human and ruminant follicles in vitro and are incompatible with
      the requirements for primordial follicle growth activation. At present, the best
      option available for the complete growth and maturation of oocytes in vitro is to
      develop an extended multistage culture strategy which will provide a complex
      support system that closely resembles the ovary in vivo. In an attempt to achieve
      this goal primordial follicle growth is first initiated and maintained to the
      preantral stages through the culture of thin slices of ovarian cortex. The
      isolation and continued culture of these preantral follicles will support antral
      cavity formation and the induction of differentiated function in the somatic cell
      compartment. Finally, after exposure to an appropriate steroid milieu in vitro it
      should be possible to induce nuclear and cytoplasmic maturation in the fully
      grown oocytes. The prospects of succeeding at each stage, and of finally
      producing a fertile gamete, are likely to be increased by preserving cellular
      interactions and the phenotype of follicle cells as these provide the
      physiological environment in which oocytes develop. Although the technology for
      the in vitro maturation (IVM) of fully grown oocytes has been exploited
      successfully in ruminants, in human assisted reproduction IVM is still
      experimental as the efficiency of IVM is low and only a small number of
      pregnancies and live births have been reported. Thus, although complete in vitro
      growth and maturation may be achieved eventually, immediate goals must include
      the optimization of methods for isolating and culturing oocytes at both ends of
      the size spectrum and the full evaluation of the normality of the oocytes grown
      for extended periods in vitro.

PMID- 14635955
TI  - The differential secretion of FSH and LH: regulation through genes, feedback and
      packaging.
AB  - While the role of oestradiol and progesterone in the control of GnRH pulsatile
      secretion and generation of the preovulatory GnRH surge to induce release of the
      LH surge has been fully investigated, less attention has been given to changes in
      the pituitary gland that may sensitize gonadotrophs to switch from pulsatile
      release to surge release of LH, in particular. Furthermore, in the follicular
      phase while pulsatile secretion of LH is maximal, FSH secretion is reduced, yet
      both hormones are produced by the same gonadotrophs. The mechanisms whereby this
      differential release can occur are still unclear. The main regulator of FSH
      secretion is through the negative feedback effects of oestradiol and inhibin,
      which directly affect FSHbeta mRNA content and subsequent synthesis of FSH. FSH
      is then released predominantly via a constitutive pathway and the amount released
      is closely related to the rate of synthesis. In contrast, while basal LH
      secretion occurs via a constitutive pathway, the principal release of LH through
      pulsatile secretion is through the regulated pathway with GnRH stimulating the
      release of pre-synthesized LH contained in storage granules without significant
      changes in LHbeta mRNA. Secretogranin II (SgII) is associated with LH in these
      electron-dense storage granules and LH-SgII granules appear to be the principal
      form of granule released in response to GnRH through the regulated pathway. At
      the time of the preovulatory LH surge, granule movement to the gonadotrope cell
      membrane abutting a capillary, polarization, appears to play an important part in
      the priming mechanism for release of LH during the preovulatory LH surge in
      response to the GnRH surge. As there appears to be limited or no gonadotroph cell
      division in the adult pituitary gland, each gonadotroph passes through this
      synthesis and secretion pathway repeatedly through successive oestrous cycles.
      Packaging of LH and FSH into different secretory granules within the same cell is
      thus pivotal for the differential secretion of these gonadotrophins.

PMID- 14635956
TI  - Reprogramming the genome: role of the cell cycle.
AB  - In nuclear transfer reconstructed embryos, the co-ordination of donor nuclear and
      recipient cytoplasmic cell cycle phases is essential to maintain ploidy and
      prevent DNA damage. However, the stage of the cell cycle at the time of
      reconstruction and the method of reconstruction may also have a significant
      impact on the subsequent development of the embryo and fetus through a number of
      other mechanisms. This paper reviews some of the information currently available
      and proposes that consideration of the cell cycle may lead to improvement of
      methods for embryo reconstruction.

PMID- 14635958
TI  - Reproduction in domestic ruminants V. Overview.

PMID- 14635957
TI  - Gene targeting in livestock.
AB  - The development of nuclear transfer from tissue culture cells in livestock made
      it possible in principle to produce animals with subtle, directed genetic changes
      by in vitro modification of nuclear donor cells. In the short period since
      nuclear transfer was first performed, gene targeting in livestock has become a
      reality. Although gene targeting has immediate potential in biotechnology, it is
      unclear whether there are practical agricultural applications, at present. The
      first livestock targeting experiments have been directed at engineering animals
      either to render their organs immunologically compatible for human
      transplantation, or for improving the commercial production of recombinant
      proteins in the transgenic mammary gland. All successful examples of targeting
      have involved target loci that are expressed in the nuclear donor cell line. Two
      important barriers to the further development of this technology are adapting
      protocols for non-expressed genes and modifying procedures to enhance the
      lifespan of targeted cells in vitro. This review provides data that illustrate
      the difficulty in targeting non-expressed genes and discusses some of the
      practical issues associated with providing targeted nuclear donor cells that are
      competent for nuclear transfer.

PMID- 14635959
TI  - What is your diagnosis? Chrondroblastic osteosarcoma.

PMID- 14635960
TI  - Long-term follow-up of dogs with patent ductus arteriosus.
AB  - Postocclusion survival data from dogs with left-to-right shunting patent ductus
      arteriosus (PDA) was available from 80 dogs, diagnosed from 1990 to 2000. Of
      these, 37 had undergone a procedure to close the ductus and were re-evaluated at
      the time of this study; clinical data from the follow-up examination was compared
      with that from the original examination. Radiographically, the right ventricle
      remained apparently enlarged, and the aortic bulge associated with dilation of
      the descending aorta did not disappear after closure. On M-mode echocardiography,
      left ventricular chamber diameter in diastole and systole and left ventricular
      posterior wall in systole decreased significantly. Mitral endocardiosis was a
      common feature. Residual flow was evident in 46 per cent of the animals. Late
      closure occurred in 8 per cent of the dogs, and trivial recanalisation in 19 per
      cent. The maximum survival time postclosure was 168 months and, after non
      occlusion, 114 months, suggesting that dogs with PDA follow an unpredictable
      course. However, there was a significant difference in survival times between the
      corrected and non-corrected group.

PMID- 14635961
TI  - Risk factor analysis and relative supersaturation as tools for identifying
      calcium oxalate stone-forming dogs.
AB  - Twenty-four hour urine samples were collected from 17 calcium oxalate (CaOx)
      stone-forming (SF) dogs and 17 normal (N), age-, breed- and sex-matched dogs.
      Urinary CaOx relative supersaturation (RSS) was calculated and found to be
      significantly higher in the SF group than the N group. RSS measurement is not
      readily applicable to veterinary practice; thus, alternatives were explored.
      Discriminant analysis failed to identify key factors differentiating most SF from
      N dogs. Urinary calcium, oxalate and uric acid, which differed between the SF and
      N animals, were combined into a measure of relative probability of CaOx stone
      formation (PSF) to establish whether this approach could be used to assess the
      risk of CaOx stone formation in dogs. Although there was good correlation between
      the techniques, RSS more clearly discriminated between SF and N dogs. These data
      suggest that neither PSF nor discriminant analysis is preferable to RSS for
      assessing the risk of CaOx stone formation in dogs.

PMID- 14635962
TI  - Suspected pituitary apoplexy in a German shorthaired pointer.
AB  - Pituitary apoplexy is a syndrome which has been described in humans caused by
      acute haemorrhage or infarction within a pituitary tumour or a non-tumorous
      pituitary gland. This report describes the authors' observations of a dog in
      which vomiting, visual disturbances, seizures, altered consciousness and
      diencephalic dysfunction occurred in association with haemorrhage originating
      from a pituitary macroadenoma. The clinical signs were thought to be consistent
      with disruption of the hypothalamus and brainstem, together with raised
      intracranial pressure due to intraventricular haemorrhage. These signs, and the
      pathological findings, bear a striking resemblance to those associated with the
      syndrome of pituitary apoplexy, seen in humans.

PMID- 14635963
TI  - Left ventricular myxosarcoma in a dog.
AB  - An entire male Neopolitan mastiff, aged two years and eight months, presented
      with a history of chronic diarrhoea and weight loss. The diarrhoea had been
      present for approximately 12 months and had progressively worsened, with weight
      loss developing over an eight-week period prior to presentation. No primary
      gastrointestinal or metabolic cause for the diarrhoea could be identified.
      Echocardiography revealed a large, multilocular, cyst-like structure within the
      pericardium compressing the heart and displacing it to the right. The mass was
      surgically excised from the left ventricular myocardium. Histopathological
      examination showed it to be a low-grade malignant myxosarcoma. The dog made a
      full recovery and was still clinically normal nine months postoperatively, with
      no evidence of tumour recurrence or metastases. However, 11 months postsurgery,
      the clinical signs of diarrhoea and weight loss returned. Tumour recurrence with
      local metastasis was diagnosed and the dog was euthanased 358 days after the
      original surgery.

PMID- 14635964
TI  - Retroflexion of the urinary bladder associated with a perineal hernia in a female
      cat.
AB  - A case of retroflexion of the urinary bladder into a bilateral perineal hernia in
      a female domestic shorthaired cat, three weeks postpartum, is reported. The
      bladder was repositioned and a cystopexy performed. A pelvic ostectomy was also
      carried out in order to alleviate the narrowing of the pelvic canal caused by an
      untreated acetabular fracture. Bilateral perineal herniorrhaphy was performed.

PMID- 14635965
TI  - Progressive myoclonus epilepsy in a beagle.
AB  - A nine-year-old, neutered female beagle was presented with a history of
      progressive myoclonic jerks. Clinical signs included mental depression and
      paroxysmal jerks of the head and forelimbs, apparently elicited by changes in
      light, noise or movements. Electroencephalographic findings were in accordance
      with myoclonus epilepsy. Postmortem histopathological findings included multiple
      periodic acid-Schiff-positive inclusion bodies throughout the central nervous
      system, but especially in the cerebellum, confirming the suspected diagnosis of
      Lafora's disease.

PMID- 14635966
TI  - Treatment of congestive heart failure.

PMID- 14635967
TI  - Addressing the welfare needs of exotic pets.

PMID- 14635969
TI  - Do hormones play a role in canine cruciate disease?

PMID- 14635970
TI  - Infection control of lung function equipment: a practical approach.
AB  - The degree of risk of cross-infection of patients via lung function testing
      equipment has yet to be quantified. Based on current evidence, elaborate
      precautions are not justified for the majority of patients attending the
      laboratory, but attention to appropriate routine cleaning and disinfection
      protocols is important. Disinfection and sterilization can be achieved by a
      variety of methods, although chemical methods should be used with caution.
      Identification of factors increasing the susceptibility or infectivity of
      particular patients is important in determining appropriate precautions. Where
      patients are known to be infectious or are immunocompromized, additional
      precautions such as using a barrier filter may be appropriate. However, because
      of cost constraints, the routine use of barrier filters is difficult to justify
      based on current evidence of minimal cross-infection associated with lung
      function equipment. Until further studies have been conducted to quantify the
      degree of risk of cross-infection that lung function test equipment poses, the
      recommendations given in this review provide a practical approach to dealing with
      this problem.

PMID- 14635971
TI  - Do asthma patients in general practice profit from a structured allergy
      evaluation and skin testing? A pilot study.
AB  - BACKGROUND: Although allergy is central to the pathophysiology of asthma, little
      is known about the benefits of a structured approach to allergen diagnosis and
      management in primary care asthma patients. OBJECTIVES: We studied effects of a
      structured allergen evaluation and allergen avoidance advice combined with or
      without additional allergy skin testing on health status, illness perception, and
      lung function of asthma patients treated in general practice. METHOD: Fifty-four
      asthma patients were randomly assigned to three groups: (i) Standard asthma care
      with information on the stepwise treatment approach, a written action plan, and
      inhaler technique training; (ii) Additional structured allergen evaluation and
      avoidance advice; (iii) Additional structured allergen evaluation and avoidance
      advice based on skin prick test results. Patients were seen for one initial
      appointment at a primary care asthma clinic and a follow-up examination 3 months
      later. On both occasions, questionnaire measures of symptoms, illness perception,
      and the perceived control of asthma were administered. Lung function was measured
      by spirometry (PEF, FEV1). Perceived allergic asthma triggers, the trigger
      impact, and the trigger control were assessed in both intervention groups.
      RESULTS: Following intervention, a decrease in beta-adrenergic inhaler use, an
      increase in the perceived control of asthma, and a decrease in the bothering from
      asthma symptoms were observed for all three groups. Intervention groups showed a
      higher awareness of animal-allergic triggers, and the perceived control of asthma
      triggers was increased in the group receiving no skin tests. FEV1 showed an
      improvement in both intervention groups. CONCLUSION: Structured allergy
      evaluation and avoidance advice can improve lung function and the control of
      asthma in primary care. Further research is needed on the additional benefits of
      allergy skin testing.

PMID- 14635972
TI  - Exhaled breath condensate acidification in acute lung injury.
AB  - Lung injury in ventilated lungs may occur due to local or systemic disease and is
      usually caused by or accompanied by inflammatory processes. Recently,
      acidification of exhaled breath condensate pH (EBC-pH) has been suggested as
      marker of inflammation in airway disease. We investigated pH, ammonia, Lactate,
      pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification:
      ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated
      patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001).
      NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated
      with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6:
      r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic
      inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury
      (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54,
      P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and
      EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances
      of regulatory mechanisms, such as glutaminase systems may result in EBC
      acidification. EBC-pH is suggested to represent a marker of acute lung injury
      caused by or accompanied by pulmonary inflammation.

PMID- 14635973
TI  - Topical tetracaine prior to arterial puncture: a randomized, placebo-controlled
      clinical trial.
AB  - The objective of this randomized, double-blind, placebo-controlled clinical trial
      was to determine whether a topical anesthetic agent (tetracaine) provides
      effective local analgesia prior to radial arterial puncture. Tetracaine or
      placebo gel was applied 45 min prior to arterial puncture to patients who were
      referred for elective arterial blood gas. The primary outcome was the patient's
      perception of pain associated with the procedure as measured by a visual analog
      scale. Fifty patients were randomized into the study, 24 received tetracaine and
      26 placebo. Mean pain score on the visual analog scale was 26.2 +/- 32.6 for the
      tetracaine-treated patients and 23.8 +/- 27.4 for the placebo-treated patients (P
      = 0.78). Mean time from the first skin puncture to successful procurement of 1 ml
      of arterial blood was 70 +/- 103s in the tetracaine group and 49 +/- 48s in the
      placebo group (P = 0.40). Difficulty of arterial puncture as assessed by the
      respiratory therapist performing the test was identical for the two groups (P =
      0.86). We conclude that tetracaine gel did not decrease patient's perception of
      pain associated with arterial puncture, nor did its use facilitate the ABG
      procedure.

PMID- 14635974
TI  - Transbronchial needle aspiration: initial experience in routine diagnostic
      bronchoscopy.
AB  - BACKGROUND: Transbronchial needle aspiration (TBNA) has been shown to be useful
      not only for the diagnosis and staging of lung cancer, its most widely studied
      indication, but also for many of other clinical indications. Despite this, it
      remains largely underutilized, mainly because of concerns with poor yield,
      safety, lack of experience of the bronchoscopist, and lack of cytopathological
      support. OBJECTIVE: To study the clinical utility and yield of TBNA as an adjunct
      to other conventional procedures in diagnostic bronchoscopy at a centre that was
      relatively inexperienced with this technique, but where there was availability of
      rapid on-site evaluation (ROSE). Most of the major indications for TBNA in both
      malignant as well as benign disease were included. SETTING: University Teaching
      Hospital naive to the procedure. PATIENT AND METHODS: Forty-five consecutive
      patients who underwent TBNA as part of diagnostic bronchoscopy during a 2-year
      study period. RESULTS: TBNA gave a yield of 65% for evaluation of mediastinal
      disease, both benign and malignant. The overall diagnostic utility for all
      indications was 71% and there were no complications. CONCLUSIONS: We conclude
      that TBNA is a useful and safe adjunct to diagnostic bronchoscopy in routine
      clinical practice. It has a satisfactory yield even with an inexperienced team,
      if used with ROSE.

PMID- 14635975
TI  - Lower respiratory tract infections in chronic obstructive pulmonary disease
      outpatients with tracheostomy and persistent colonization by P. aeruginosa.
AB  - Outpatients with tracheostomy can be managed with a low risk for severe airways
      infections despite colonization with pathogenic bacteria. No studies have been
      focused on chronic obstructive pulmonary disease (COPD), a condition known for
      recurrent exacerbations. The aim of our study was to verify whether at follow-up
      in tracheostomized COPD versus other disease outpatients, persistent P.
      aeruginosa colonization may influence the rate and treatment of lower respiratory
      tract infections (LRTI) or hospital admissions. Thirty-nine outpatients were
      considered: 24 were affected by COPD (age 66, 54-78 years, mean, range), 15 by
      restrictive lung disease (RLD) (57, 41-72 years). During an 18-month follow-up
      the number of LRTIs were recorded. Bacterial identifications were assessed at
      baseline and every month for 6 months in bronchial aspirates. The number of LRTI
      per patient was not significantly different between COPD [37, 1(0-6)] and RLD
      [18, 1(0-5)], [total, median (range)]. Persistent P. aeruginosa colonized 18 COPD
      (75%), 12 RLD patients (86%) and was not associated with an increased number of
      LRTI: 1(0-6) and 1(0-2), respectively. There were no differences in the number of
      hospital admissions: COPD 0(0-2), RLD 1(0-1), with a significant decrease versus
      before tracheostomy (P < 0.001). In conclusion, the rate of LRTI and hospital
      admissions in COPD outpatients with chronic tracheostomy was low, similar to non
      COPD patients and independent of P. aeruginosa colonization.

PMID- 14635976
TI  - Health related quality of life in individuals with asthma related symptoms.
AB  - BACKGROUND: Where evidence is required for disease-area prioritisation (e.g. by
      national policymakers), impact on health related quality of life (HRQoL) can be
      considered equitably across diseases using quantitative data from generic HRQoL
      instruments. Before this can take place, it must be shown that the instrument
      captures HRQoL impairment associated with each disease area. AIM: To ascertain
      whether the HRQoL impairment associated with respiratory disease can be
      represented by responses to EQ-5D, a generic HRQoL questionnaire. METHOD: EQ-5D
      and a respiratory health questionnaire were sent to 10,471 adults registered with
      two general practices in Manchester, UK. EQ-5D examines 5 domains (mobility, self
      care, usual activities, pain/discomfort and anxiety/depression) and includes an
      overall rating via visual analogue scale. Societal valuations of domain responses
      were also considered. RESULTS: HRQoL was substantially reduced in respondents who
      were likely to have obstructive airways disease (mean EQ-5D(index) 0.63 compared
      to 0.82, t-test P < 0.001; mean EQ-5D(vas) 62.7 compared to 77.6, t-test P <
      0.001) and was negatively associated with respiratory symptoms, older age and
      female gender. The association with respiratory problems remained following
      stratification by age and gender. The deficit in HRQoL associated with increasing
      age was more pronounced in those likely to have obstructive airways disease.
      CONCLUSION: HRQoL measured using EQ-5D is substantially reduced in respondents
      with respiratory symptoms enabling use of the instrument in inter-disease
      comparisons.

PMID- 14635977
TI  - Social deprivation and hospital admission for respiratory infection: an
      ecological study.
AB  - STUDY OBJECTIVE: To examine the relationship between social deprivation and risk
      of hospital admission for respiratory infection. METHODS AND SUBJECTS: Ecological
      study using hospital episode statistics and population census data. Cases were
      residents of the West Midlands Health Region admitted to hospital with a
      diagnosis of respiratory infection, acute respiratory infection, pneumonia or
      influenza over a 5-year period. Postcodes of cases were used to assign Townsend
      deprivation scores; these were then ranked and divided into five deprivation
      categories. Poisson regression analysis was used to estimate the magnitude of
      effect for associations between deprivation category and hospital admission by
      age and admitting diagnosis. MAIN RESULTS: There were 136755 admissions for
      respiratory infection, equivalent to an annual admission rate of 27.1 per 1000
      population (95% CI = 26.9-27.2). Deprivation was associated with increased
      admission rates for all respiratory infection (P < 0.0001) and affected all age
      groups. The greatest effect was in the 0-4 years age-group with admission rates
      91% higher in the most deprived children compared to the least deprived. Hospital
      admissions for acute respiratory infection and pneumonia were both significantly
      associated with deprivation (P < 0.0001). CONCLUSIONS: Respiratory infection is
      associated with social inequalities in all age-groups, particularly in children.
      Prevention of respiratory infection could make an important contribution to
      reducing health inequalities.

PMID- 14635978
TI  - High levels of urinary leukotriene E4 excretion in steroid treated patients with
      severe asthma.
AB  - Urinary LTE4 reflects the whole body production of the cysteinyl-leukotrienes
      (LTC4, LTD4 and LTE4) that are established mediators in asthma. The influence of
      chronic inhaled and oral glucocorticoid treatment on urinary excretion of
      leukotriene (LT) E4 was investigated in subjects with asthma. Enzyme immunoassay
      analysis of LTE4 was performed in spot urine samples collected from 40 patients
      with severe asthma, 25 patients with mild-moderate asthma and 20 non-asthmatic
      control subjects. Urinary LTE4 was significantly higher in patients with severe
      asthma (69.7 +/- 5.5) as compared to mild-moderate asthma (45.7 +/- 3.3 with P <
      0.0004) and control (42.5 +/- 2.5 with P < 0.0001). Despite chronic systemic
      treatment with glucocorticoids, chronically severe asthma had presented with
      higher levels of LTE4 compared to mild moderate asthma and healthy controls. The
      findings support previous indications that one important component in asthmatic
      airway inflammation, the cysteinyl-leukotriene pathway remains relatively
      unopposed by oral glucocorticoids.

PMID- 14635979
TI  - Significance of plasma N-terminal pro-brain natriuretic peptide in patients with
      systemic sclerosis-related pulmonary arterial hypertension.
AB  - OBJECTIVES: A single centre pilot study to investigate the role of the plasma N
      terminal pro-brain natriuretic peptide (N-T proBNP) assay to risk stratify
      patients with suspected pulmonary arterial hypertension (PAH) from a background
      SSc population. METHODS: Out of 49 SSc patients, 23 had and 26 did not have PAH.
      Right ventricular haemodynamic variables, six-minute walk test and plasma N-T
      proBNP levels were recorded from patients catheterised for suspected PAH (23 with
      PAH and 11/26 without PAH). RESULTS: Mean value of N-T proBNP for SSc patients
      with PAH was 3365 (standard error 1095) pg/ml compared to 347 (174) pg/ml for
      patients without PAH. There was a statistically significant correlation (P <
      0.05) between N-T proBNP values and (i) mean pulmonary artery pressure (r =
      0.53), (ii) right ventricular end diastolic pressure (r = 0.59) and (iii)
      pulmonary vascular resistance (r = 0.49). Receiver operator characteristic curve
      analysis showed that a cut-off value of 395.34 pg/ml had a sensitivity of 0.69
      and specificity of 1.0. CONCLUSIONS: N-T proBNP estimation in systemic sclerosis
      related pulmonary hypertension is a potentially useful diagnostic tool with a
      high specificity and negative predictive value. This test has the potential to
      have an important role in risk stratification and monitoring of therapy in the
      future.

PMID- 14635980
TI  - Lung function in patients with chronic airflow obstruction due to tuberculous
      destroyed lung.
AB  - Lung function in cases of chronic airflow obstruction (CAO) due to tuberculous
      destroyed lung, which is still common in Korea, has not been objectively
      investigated. We evaluated lung functions and postbronchodilator responses in 21
      CAO patients with a forced expiratory volume in 1 s (FEV1) of 30-65% of the
      predicted value, and compared some of these results with those of age-, sex- and
      FEV1% predicted-matched patients with chronic obstructive pulmonary disease
      (COPD). In addition, we analyzed the lung functions of CAO patients with respect
      to wheezing. The forced vital capacity (FVC) (P < 0.05) and postbronchodilator
      FEV1 of CAO patients were lower than those of COPD patients (P < 0.05). When a
      positive bronchodilator response was defined as an absolute change of FEV1 (FEV1
      delta(abs)) of more than 0.2 l (P < 0.05) and a percentage of initial FEV1 (FEV1
      delta%init) of more than 12%, the positive rates in CAO patients were lower than
      in COPD patients (P < 0.05). Among the CAO patients, patients with wheezing
      showed lower forced expiratory flow 25%-75% (FEF(25-75%)) (P < 0.05) and higher
      airway resistance than those without wheezing (P < 0.05). CAO patients with
      wheezing were more responsive to bronchodilator than those without wheezing.
      Although the pathophysiology of CAO differs from that of COPD, bronchodilator
      therapy could be useful for treating CAO, especially in cases presenting with
      wheezing.

PMID- 14635981
TI  - Recent progress in polymeric gene delivery systems.
AB  - Considerable progress in polymeric gene delivery systems has been made over the
      last several years. First generation polymers have been replaced by safer and
      more efficient carrier systems through molecular functionalization, improving
      polymer biocompatibility, biological stability, cell-specificity, and
      intracellular trafficking. Many new polymers have moved from in vitro
      characterization to preclinical validation in animal models of cancer, diabetes,
      and cardiovascular disorders. Although the transfection efficiency of most
      polymeric carriers is still significantly lower than that of viral vectors, their
      structural flexibility allows for continued improvement in polymer activity.
      Also, simple manufacturing and scale-up schemes and the low cost of manufacturing
      are likely to eventually compensate for the performance gap between viral and
      polymeric vectors and establish clinical recognition and commercialization of
      polymer-based gene therapy drugs.

PMID- 14635982
TI  - Polyphosphates and other phosphorus-containing polymers for drug delivery
      applications.
AB  - Poly(phosphate ester)s, polyphosphonates, and polyphosphazenes are three classes
      of phosphorus-containing polymers that have received wide attention over the past
      decade for their utility in biomedicine and tissue engineering. These three
      families of polymers can lead to a number of subclasses of polymers with varied
      properties. Significant research in this area has led to niche polymers with
      morphologies ranging from viscous gels to amorphous microparticles for utility in
      drug delivery. Furthermore, the pentavalency of phosphorus offers the potential
      for covalent linking of the drug. The classes of polymers discussed in this
      review are being explored in human clinical trials for vaccine delivery as well
      as delivery of oncolytic and CNS therapeutics. More applications in the areas of
      DNA delivery and tissue engineering are also being explored.

PMID- 14635983
TI  - Four decades of community mental health: a symphony in four movements.
AB  - The authors present a detailed chronological discussion of the evolution of
      community mental health care in the United States with emphasis on the period of
      the 40 years since the passage of the Community Mental Health Centers
      Construction Act of October 31, 1963.

PMID- 14635984
TI  - The evolution of systems of care for children's mental health: forty years of
      community child and adolescent psychiatry.
AB  - Over the past 20 years, child and adolescent community mental health has evolved
      conceptually, clinically, and scientifically towards the community-based systems
      of care model. This model asserts important values and principles, including the
      centrality of the child and family in the care process, the integration of the
      efforts of disparate agencies and interveners into a contextual approach, and the
      importance of serving children with serious disturbances in their homes and
      communities. The article reviews the evolution of the community-based systems of
      care model, its evidence-base, its application in practice, and the challenges it
      faces in today's human services environment.

PMID- 14635985
TI  - The history of community mental health treatment and rehabilitation for persons
      with severe mental illness.
AB  - The authors review the evolution of the treatments for persons with severe mental
      illnesses over the past 40 years in three areas: pharmacological and other
      somatic treatments, psychosomatic treatments, and rehabilitation. Current
      treatments are based on a much stronger evidence base, are more patient-centered,
      and are more likely to target autonomy and recovery.

PMID- 14635986
TI  - The legend and lessons of Geel, Belgium: a 1500-year-old legend, a 21st-century
      model.
AB  - Geel, Belgium, is the home of a legendary system of foster family care for the
      mentally ill. The current status of Geel's modern system of integrated community
      care and the 700-year history of this system (including the 10-year-long,
      international, multi-disciplinary Geel Research Project) are described. As a case
      study, Geel offers a microcosmic encapsulation of major issues related to mental
      illness. Though these issues have been dealt with across time and in all places,
      here they are contained in a single community. This is a case study that can help
      other communities to identify significant factors that contribute to successful
      community mental health programs.

PMID- 14635987
TI  - The future of community psychiatry.
AB  - Leaders of national groups that have focused on issues of community and social
      psychiatry present their ideas about the future of psychiatry. They identify five
      areas: theory development; the relevance of community psychiatry in the 21st
      century; education and training; the relationship between community psychiatry
      and health maintenance organizations; and role of community psychiatry in
      bridging medical science with humanism. The unifying theme for these topics is
      that community psychiatry can be a vehicle for modifying general psychiatry's
      propensity towards individualism and reductionism by offering a more holistic and
      integrative approach to illness and well-being.

PMID- 14635988
TI  - The use of pulsed electromagnetic fields with complex modulation in the treatment
      of patients with diabetic polyneuropathy.
AB  - Clinical and electroneuromyographic studies were performed in 121 patients with
      diabetic polyneuropathy (DPN) before and after courses of treatment with pulsed
      electromagnetic fields with complex modulation (PEMF-CM) at different frequencies
      (100 and 10 Hz). Testing of patients using the TSS and NIS LL scales demonstrated
      a correlation between the severity and frequency of the main subjective and
      objective effects of disease and the stage of DPN. The severity of changes in the
      segmental-peripheral neuromotor apparatus--decreases in muscle bioelectrical
      activity, the impulse conduction rate along efferent fibers of peripheral nerves,
      and the amplitude of the maximum M response--depended on the stage of DPN and the
      duration of diabetes mellitus. The earliest and most significant
      electroneuromyographic signs of DPN were found to be decreases in the amplitude
      of the H reflex and the Hmax/Mmax ratio in the muscles of the lower leg.
      Application of PEMF-CM facilitated regression of the main clinical symptoms of
      DPN, improved the conductive function of peripheral nerves, improved the state of
      la afferents, and improved the reflex excitability of functionally diverse
      motoneurons in the spinal cord. PEMF-CM at 10 Hz was found to have therapeutic
      efficacy, especially in the initial stages of DPN and in patients with diabetes
      mellitus for up to 10 years.

PMID- 14635989
TI  - Perceptual binding of sensory events: the inclusive characteristics model.
AB  - A conceptual model of a perceptual system is proposed, in which each neural level
      forms characteristics inclusive of the data held in the underlying level. As a
      result, the stimulus field can be expressed as a hierarchically ordered set of
      overlying sensory characteristics: from sensory features to higher inclusive
      characteristics binding sensory data to form whole images and scenes. Specific
      patterns of electrical activity reflecting inclusive characteristics are
      transmitted via reverse projections from the upper neural levels to the lower.
      This forms a downward excitation transmission cascade, stimulating those neural
      structures whose signals correspond to the higher inclusive characteristics of
      the given perceptual act. It is demonstrated that these mechanisms are in good
      agreement with experimental data obtained from psychological and
      neurophysiological studies and may support the binding of sensory events at all
      perceptual levels.

PMID- 14635990
TI  - Long-term potentiation and evoked spike responses in the cingulate cortex of
      freely mobile rats.
AB  - Long-term potentiation of synaptic efficiency is regarded as a major candidate
      for the role of the physiological mechanism of long-term memory. However, the
      limited development of concepts of the cellular and subcellular characteristics
      of the induction of long-term potentiation in animals in conditions of free
      behavior does not correspond to the importance of this question. The present
      study was undertaken to determine whether the characteristics of potentiation in
      the cingulate cortex in response to stimulation of fibers of the subiculo
      cingulate tract are truly long-term, i.e., develop through all known phases and
      last at least 24 h, in freely moving animals. In addition, the study aims
      included identification of the effects of application of blockers of different
      types of glutamate receptors on the development of long-term potentiation and
      identification of the characteristics of spike responses of single cingulate
      cortex neurons to stimulation of the subiculo-cingulate tract. Long-term
      potentiation, lasting more than 24 h, was obtained in freely moving adult rats
      not treated with GABA blockers. Injection of glutamate NMDA synapse blockers led
      to significant decreases in evoked cingulate cortex potentials in response to
      test stimulation. Activatory short-latency spike responses were characterized by
      a low probability of spike generation, and this increased with increases in the
      stimulation current. These data demonstrated that it is methodologically possible
      to compare, in freely moving rats, the involvement of individual neurons in the
      mechanisms involved in learning one or another type of adaptive behavior and the
      dynamics of their evoked spike activity during the formation of long-term
      potentiation.

PMID- 14635991
TI  - Neuroendocrine mechanisms of development of experimental hyperandrogen-induced
      anovulation.
AB  - An experimental model of hyperandrogen-induced anovulatory infertility (s.c.
      implantation of Silastic capsules containing testosterone into adult female rats)
      was used to study morphological, hormonal, and biochemical measures
      characterizing the state of the hypothalamo-hypophyseal-ovarian system.
      Impairments in functional androgen metabolism in the hypothalamus were seen, with
      decreases in the Luliberin sensitivity of the hypophysis, changes in the
      structure of estral cycles, and morphological changes in the ovaries; these
      findings are evidence for neuroendocrine disturbances in the control of
      ovulation. Flutamide, an experimental antiandrogen, led to partial normalization
      of the hormonal, biochemical, and morphological characteristics, as well as to
      recovery of fertility in females with anovulatory infertility.

PMID- 14635992
TI  - Involvement of the nucleus accumbens in the formation of spatial selection
      reactions in rats in a radial maze.
AB  - Studies on rats demonstrated that lesioning of the medial shell of the nucleus
      accumbens led to impairment of the ability of experimental rats to perform error
      free identification of the arm containing the largest amount of reinforcement in
      a radial maze. The behavioral deficit was not associated with impaired motivation
      or sensorimotor learning ability, as there was no such deficit in operated rats
      during sequential presentation of local discriminant stimuli identifying the
      location of the forthcoming reinforcement. These data suggest that the medial
      shell of the nucleus accumbens, which receives convergent projections from the
      ventral hippocampus, amygdala, and ventral tegmental area, plays an important
      role in organizing the spatial orientation of the animal in the direction of the
      preferred reinforcement in conditions of a sensory information deficit.

PMID- 14635993
TI  - Hyperoxic vasoconstriction in the brain is mediated by inactivation of nitric
      oxide by superoxide anions.
AB  - The hypothesis that decreases in brain blood flow during respiration of
      hyperbaric oxygen result from inactivation of nitric oxide (NO) by superoxide
      anions (O2(-)) is proposed. Changes in brain blood flow were assessed in
      conscious rats during respiration of atmospheric air or oxygen at a pressure of 4
      atm after dismutation of O2(-) with superoxide dismutase or suppression of NO
      synthesis with the NO synthase inhibitor L-NAME. I.v. administration of
      superoxide dismutase increased brain blood flow in rats breathing air but was
      ineffective after previous inhibition of NO synthase. Hyperbaric oxygenation at 4
      atm induced decreases in brain blood flow, though prior superoxide dismutase
      prevented hyperoxic vasoconstriction and increased brain blood flow in rats
      breathing hyperbaric oxygen. The vasodilatory effect of superoxide dismutase in
      hyperbaric oxygenation was not seen in animals given prior doses of the NO
      synthase inhibitor. These results provide evidence that one mechanism for
      hyperoxic vasoconstriction in the brain consists of inactivation of NO by
      superoxide anions, decreasing its basal vasorelaxing action.

PMID- 14635994
TI  - The effects of novelty and behavioral stereotype on the development of amnesia in
      mice.
AB  - The aim of the present study was to analyze the significance of the interaction
      between the basic behavioral strategy, the extinction of the novelty of
      information, and the efficacy of amnesia-inducing influences. Using a combination
      of training to passive avoidance with holding the animal in the unsafe sector of
      the apparatus, comparative analysis was performed of the reproduction of a memory
      trace in aggressive and submissive mice of line C57BL/6J with and without six
      sessions of familiarization with the apparatus. These experiments showed that
      preliminary habituation prevented the development of amnesia in submissive but
      not aggressive individuals. The cause of these differences in the effects of
      preexposure on the development of amnesia involves the selectivity of the process
      of extinction of information novelty characteristic for the behavioral
      stereotype.

PMID- 14635995
TI  - Mechanisms of the effects of adrenocorticotropic hormone on pain sensitivity in
      rats.
AB  - Experiments on anaesthetized male Sprague-Dawley rats were performed to study the
      effects of adrenocorticotropic hormone (ACTH) on pain sensitivity. Systemic
      administration of ACTH to animals with normal hormone production induced rapidly
      developing (starting at 3 min) and prolonged (30 min) increases in pain response
      thresholds. Blockade of opiate receptors led to suppression of the initial stage
      of the analgesic effect of ACTH: the response was seen only from 15 to 30 min. In
      animals with deficient glucocorticoid production, the duration of the analgesic
      action of ACTH decreased to 15 min. Analgesia was completely eliminated by the
      combination of suppression of glucocorticoid production and blockade of opiate
      receptors. The analgesic effect of ACTH was mediated by two mechanisms: 1) a
      rapidly-acting (from 3 to 15 min) mechanism associated with opiate receptors and
      not related to glucocorticoids, and 2) a delayed (from 15 to 30 min) mechanism
      associated with glucocorticoids but not opiate receptors.

PMID- 14635996
TI  - Status of the "protein kinase CK2-HMG14" system in age-related amnesia in rats.
AB  - The experiments described here demonstrate that disruption of the phosphorylation
      of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class
      may be the cause of decreased gene expression in age-related cognitive deficits.
      Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24
      months old) was accompanied by decreases in the synthesis of synaptosomal
      proteins and transcription in nuclei isolated from cortical, hippocampal, and
      striatal neurons. There was a decrease in chromatin protein kinase CK2 activity
      and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2.
      Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5
      methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14
      phosphorylation by protein kinase CK2, increased transcription, increased the
      synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged
      rats. Thus, activation of the "protein kinase CK2-HMG14" system is accompanied by
      optimization of synaptic plasticity in aged animals. The results provide evidence
      for the high therapeutic potential of protein kinase CK2 activators.

PMID- 14635997
TI  - The advantages of electrophysiological control for the localization and selective
      lesioning of the nucleus accumbens in rats.

PMID- 14635999
TI  - Nociceptive reactions during stimulation of immunity in rats with different
      individual sensitivities to stress.
AB  - Different nociceptive reactions and individual resistance were studied in rats in
      the initial state and in conditions of stimulation of immune processes by various
      methods. The aims were to study the effect of the preparation Imunofan, an immune
      stimulator, on various behavioral manifestations of pain reactions in animals
      with different individual resistances to stress and to compare the results with
      similar data in a natural model of immune activation. Detection of the central,
      immune-dependent component of the regulation of nociceptive reactions was
      addressed using intracerebroventricular administration of the study compound.
      Studies were performed on 43 male Wistar rats. Individual resistance to stress
      was assessed by recording the free behavior of the animals in an open field test.
      The following nociceptive reactions were assessed: 1) the tail withdrawal
      reaction using the standard tail flick method; and 2) running, twitching,
      jumping, and vocalization reactions to electrical stimulation of the limbs. These
      studies demonstrated that i.m. administration of Imunofan (10 microl of 0.005%
      solution) suppressed the active behavior of the animals in the open field and
      produced hyperalgesia, with decreases in the thresholds of nociceptive reactions.
      Hyperalgesia in stress-sensitive rats were significantly greater than in
      resistant animals. Similar results were obtained in conditions of natural
      activation of immunity produced by the operative intervention needed for
      injection of the agent into the cerebral ventricle. Intracerebroventricular
      administration of Imunofan was accompanied by more marked and complex changes in
      pain sensitivity.

PMID- 14635998
TI  - Protein-peptide complexes of angiotensins in the mechanisms of thirst motivation.
AB  - A comparative analysis of the physiological actions of native angiotensin I and
      angiotensin II and protein-peptide complexes of angiotensin I and angiotensin II
      on drinking behavior in rats was performed. The protein-peptide complexes of
      angiotensin I and angiotensin II had wider spectra of physiological activity than
      the native peptides. Protein-conjugated angiotensin I, unlike the motivationally
      neutral native angiotensin I, produced marked activation of innate drinking
      behavior in mice. The protein-peptide complex of angiotensin II showed selective
      effects on acquired drinking behavior. These data are assessed with respect to
      the specific involvement of protein-peptide complexes of angiotensin I and
      angiotensin II in the mechanisms of thirst motivation during the performance of
      innate and acquired habits.

PMID- 14636000
TI  - Blood albumin in the mechanisms of individual resistance of rats to emotional
      stress.
AB  - This report describes studies of the characteristics of serum albumin in rats
      with different predicted levels of resistance to emotional stress in control
      conditions and in conditions of experimental emotional stress. The effects of
      peptides increasing the resistance of animals to emotional stress (delta sleep
      inducing peptide and Semax) on serum albumin were analyzed in rats predicted to
      be resistant and susceptible to emotional stress.

PMID- 14636001
TI  - Dynamics of neuronal, autonomic, and motor measures in animals performing an
      acquired habit.
AB  - Previously obtained results and data from other groups showing that intersignal
      activity in animals correlates with the success of acquisition of defensive and
      food-procuring behavior are presented. In addition, specific changes in neuron
      activity and in the dynamics of cardiac and respiratory activity are demonstrated
      during performance of intersignal behavioral acts. The moments of appearance of
      intersignal activity were studied, as were patterns of changes in
      neurophysiological measures during different types of intersignal actions. The
      first series of experiments showed that different contextual stimuli (mainly
      ratios of sector illumination, which are ethologically important for rats) have
      significant effects on the level of intersignal activity and the success of
      learning active defensive behavior. The next series of experiments, in which
      learning and extinction of a passive defensive habit in rabbits were performed,
      demonstrated the existence of two types of intersignal activity. The first type
      was characterized by repetition of pain reinforcement parameters in the structure
      of changes in neurophysiological measures during intersignal behavior; the second
      type was characterized by a coincidence of the whole structure of neuronal
      activity, cardiac rhythm, and respiration during intersignal activity with the
      dynamics of these measures during the conditioned reflex behavioral act. This
      study suggests that the process of intersignal extraction of an efferent program
      for acquired defensive behavior may be one of the mechanisms by which it is fixed
      in memory and plays an important role in the animal's achievement of useful
      adaptive results.

PMID- 14636002
TI  - Endogenous dopamine modulates corticopallidal influences via GABA.
AB  - Acute experiments on Sprague-Dawley rats were performed to study the effects of
      local application of D1 and D2 receptor antagonists (SCH 23390 and raclopride) on
      the responses of neurons in the globus pallidus induced by stimulation of the
      somatosensory cortex. SCH 23390 induced short-latency inhibition in response to
      stimulation of the cortex and blocked long-latency inhibition. Application of
      raclopride suppressed short-latency inhibition and induced a long-latency
      inhibitory response to stimulation of the cortex. It is suggested that these
      changes are based on modulation of GABA release from striopallidal terminals by
      endogenous dopamine.

PMID- 14636003
TI  - Useful interventions for intradialytic hypotension.

PMID- 14636004
TI  - Dialysis-related amyloidosis revisited.

PMID- 14636005
TI  - Caspase-3 and -8 activation and cytokine removal with a novel cellulose
      triacetate super-permeable membrane in an in vitro sepsis model.
AB  - Pro-apoptotic molecules are generated during sepsis which may be responsible for
      alteration of organ function in sepsis. Removal of systemic apoptotic activity
      may affect recovery from sepsis. Current high flux membranes might not be
      sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the
      elimination of pro-apoptotic factors induced by LPS in human whole blood by a
      super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka,
      Japan) in comparison to a standard high flux cellulose triacetate membrane (UT
      700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola
      Italy) in an in vitro blood circulation. We spiked human whole blood with
      lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated
      it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for
      3 hours. The UF line was first returned to the blood module at 10 min. After
      this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance
      was obtained by re-infusion of bicarbonate buffered hemofiltration fluid.
      Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate)
      by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V
      flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated
      blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were
      determined by commercially available ELISAs. Sieving coefficients and clearances
      were determined for the different cytokines. Caspase-3 and Caspase-8 were
      activated by LPS and remained either stable or increased during in vitro
      circulation. Apoptosis activity of U937 cells, when incubated with the
      ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 =
      23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity
      recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for
      Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super
      permeable membrane were significantly higher for all measured cytokines in
      comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p <
      0.001) and close to the values observed for the plasmafiltration membrane.
      Nevertheless protein losses measured by albumin leakage were much lower with the
      Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic
      factors can be eliminated by dialytic membranes with the removal rate maximized
      by using super high flux dialysers which may represent a compromise between
      hemofiltration and plasmafiltration membranes.

PMID- 14636006
TI  - Platelet loss across the hemofilter during continuous hemofiltration.
AB  - BACKGROUND: Thrombocytopenia is a common finding in patients in the intensive
      care unit receiving continuous renal replacement therapy (CRRT). It is unknown if
      the hemofilter itself contributes to the platelet loss. OBJECTIVE: To measure the
      direct effect of the hemofilter on platelet counts during CRRT. DESIGN:
      Prospective, observational study. SETTING: Intensive care unit of a University
      hospital. PATIENTS: Critically ill patients with acute renal failure receiving
      CRRT. METHODS: Two samples of blood were drawn simultaneously, pre-filter and
      post-filter, and analyzed for platelet count. A correction factor was applied to
      the post-filter platelet count to adjust for the hemoconcentrating effect of net
      ultrafiltration. RESULTS: Forty-eight sets of paired data from 22 patients were
      studied. There was a small but significant decrease in mean platelet count across
      the hemofilter. The mean platelet count drop was 2.32 x 10(9)/L (s.e. 1.06, p =
      0.0487, 95% CI (0.01, 4.62)). Blood flow was strongly related to degree of
      platelet loss, with a decreased loss of 0.07 x 10(9)/L for every ml/min increase
      in blood flow (p = 0.015). There was no overall decrease in concurrently measured
      red cell counts across the hemofilter. However, there was a machine-specific
      affect on red cell loss (p < 0.0001). The total calculated daily platelet loss
      across the filter was 625 x 10(9) cells. CONCLUSION: The hemofilter may
      contribute to the thrombocytopenia seen during CRRT, by means of either
      destruction or retention of platelets during passage. This affect appears
      attenuated by higher blood flows. This information is useful in the assessment of
      a low platelet count in patients receiving CRRT.

PMID- 14636007
TI  - Structural changes in silicon rubber peritoneal dialysis catheters in patients
      using mupirocin at the exit site.
AB  - Structural damage to polyurethane PD (peritoneal dialysis) catheters in patients
      using mupirocin ointment is widely appreciated, but damage to silicon rubber PD
      catheters is less well described. Ten catheters (6.6%) out of 152 were found to
      have structural alterations such as opacification, ballooning, thinning, and
      rupture. The duration of PD in these 10 patients ranged from 23 months to 80
      months (mean duration 51.1 months). The frequency of mupirocin application varied
      from daily (2 cases) to 2-3 times per week (7 cases). In eight catheters
      opacification occurred at the exit site whereas one catheter showed opacification
      midway between the exit site and the titanium adaptor. One catheter showed
      opacification, ballooning, and thinning at the exit site ruptured in the form of
      two slit-like openings. In conclusion, various structural changes such as
      opacification, ballooning or thinning were seen in 6.6% of silicon rubber PD
      catheters in patients using mupirocin at the exit site. Although the mechanism
      remains elusive, mupirocin or the antiseptic solution alone or in combination may
      be contributory. We believe that this is an under-reported complication and
      encourage other health care givers to incorporate a search for such changes
      during clinic visits.

PMID- 14636008
TI  - Changes in serum electrolytes during treatment of patients in liver failure with
      molecular adsorbent recirculating system.
AB  - PURPOSE: To study the effect of MARS on serum electrolytes during liver failure.
      DESIGN: Twenty-three patients admitted to a quaternary health care facility from
      September 2000 to May 2002, 22 adults and 1 child, 11 males (48%) and 12 females
      (52%), age 15-70 (median 53), treated with MARS for: 12 acute-on-chronic liver
      failure (52%); 4 fulminant hepatic failure (17%); 3 intractable pruritus (13%); 2
      primary-non-function (9%); 2 following major liver resection (9%). PROCEDURES:
      Sodium, potassium, chloride, phosphorus, calcium, and magnesium were measured in
      the serum, ultrafiltrate and albumin circuit before and after MARS. STATISTICAL
      METHODS: A comparison of electrolyte concentrations, before and after MARS, was
      performed using a paired t test. MAIN FINDINGS: Serum electrolyte concentrations
      before and after MARS, while statistically significant in some cases, were very
      small, and of no clinical relevance. CONCLUSION: MARS exchanges potassium,
      chloride, calcium, and magnesium by ultrafiltration; sodium by the albumin
      dialysis.

PMID- 14636009
TI  - "All in one" cardiopulmonary bypass circuit for aortic surgery.
AB  - We devised an "all in one" cardiopulmonary bypass circuit for aortic surgery, and
      evaluated its efficacy and safety. The circuit consisted of a venous line,
      reservoir, single centrifugal pump, membrane oxygenator and arterial line
      bifurcated into two lines for systemic perfusion and selective branch perfusion.
      The perfusion volume was regulated by an occluder and measured by a flow sensor.
      A closed partial bypass was established using a shunt line bypassing the
      reservoir. We applied this circuit to 25 patients with aortic disease. Regulation
      of both the selective cerebral perfusion (SCP) and the selective branch perfusion
      was easily performed. There was neither stroke nor organ dysfunction
      postoperatively. There are some cases in which it is difficult to decide the
      necessity for SCP preoperatively; the use of this circuit may resolve this
      problem. This circuit can be easily and safely applied to any type of aortic
      surgery.

PMID- 14636010
TI  - A chronic heart failure model by coronary artery ligation in the goat.
AB  - The availability of a reliable heart failure model in large animals is important.
      We report upon our efforts to develop a chronic heart failure model in seven
      goats using sequential ligation of the left anterior descending (LAD) coronary
      artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD
      artery was ligated, and the diagonal vessel at the same level was ligated one
      hour later. Cardiac measurements were performed with a thermodilution catheter
      and by ultrasonography. Two months after the operation, the same measurements
      were made and animals were sacrificed for postmortem examinations of their
      hearts. Hemodynamic measurements, except cardiac output, showed no significant
      changes immediately after the coronary artery ligation. Echocardiographic
      measurements showed significant changes in the ejection fraction and fractional
      shortening without changes in left ventricular dimensions. Wall motion analyses
      demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all
      animals immediately after coronary artery ligation. Five animals have undergone
      hemodynamic and ultrasonographic studies 2 months after coronary artery ligation.
      The results obtained from these animals showed significant increases in central
      venous pressure, right ventricular pressure, pulmonary artery pressure, and
      pulmonary artery capillary wedge pressure, and a significant decrease in cardiac
      output. Increases in left ventricular dimensions and decreases in ejection
      fraction with fractional shortening in ultrasonographic studies were also
      observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with
      chamber enlargement, were clearly seen with dilatation of the heart chambers in
      all specimens. Based on this study, we conclude that goats, like sheep, can
      provide a reliable model of chronic heart failure by coronary artery ligation and
      in view of the many advantages offered by goats, we believe that this animal
      model will be useful for cardiac experimentation.

PMID- 14636011
TI  - In vitro construction of urinary bladder wall using porcine primary cells
      reseeded on acellularized bladder matrix and small intestinal submucosa.
AB  - BACKGROUND: Partial or radical cystectomy requires replacement of the urinary
      reservoir normally achieved by using small or large bowel segments. Our aim was
      to establish tissue engineering of an bioartificial bladder wall using primary
      cultures of porcine urothelial (pUC) and bladder smooth muscle cells (pSMC) to be
      reseeded on different acellular biological matrices. METHODS: Primary porcine
      cultures of pUC and pSMC were established from open bladder biopsy material 25
      mm2 in size. Acellular matrix was generated either from a) porcine bladder wall
      segments or b) tubular small intestinal submucosa with the still attached
      decellularized muscularis layer. Reseeding of these matrices with primary cells
      was done in a two-dimensional static model and in a three-dimensional rotating
      bioreactor perfused with cell culture medium for a period of 6 weeks. RESULTS:
      Prior to reseeding the cultured cells were characterized as pUC and pSMC by
      immunohistochemical staining with either anti-keratin 7 or anti-alpha actin. For
      both matrices a reseeded double layer cell system of pUC and pSMC could be
      identified after incubation in the described systems for 6 weeks. CONCLUSIONS:
      Our results document successful generation of tissue engineered urinary bladder
      wall, which can be used in further large animal transplantation experiments.

PMID- 14636012
TI  - Enhanced in vitro maturation of subcultivated fetal human hepatocytes in three
      dimensional culture using poly-L-lactic acid scaffolds in the presence of
      oncostatin M.
AB  - Fetal human liver cell fractions, which contain large numbers of hepatocyte
      progenitors, have high proliferation potential in vitro. To create an engineered
      liver tissue equivalent of a clinically significant size, however, repeated
      subcultivation and functional maturation are necessary in vitro. A commercially
      available human fetal liver cell fraction that was cultivated for some time in
      vitro has been reported to lose liver specific functions almost completely. We
      therefore investigated the effects of oncostatin M (OSM) and hepatocyte growth
      factor (HGF) in long-term three-dimensional (3D) culture using macroporous poly-L
      lactic acid (PLLA) scaffolds on the restoration of such liver-specific functions
      of the fraction. 3D culture using PLLA scaffolds with OSM remarkably enhanced the
      albumin production and cytochrome P450 1A1/2 capacity with the culture time. HGF
      alone had no preferable effect on these functions even in 3D culture. Alpha
      fetoprotein production was consistently suppressed in the 3D culture compared
      with that in monolayers. This suppression was not observed in the same types of
      culture of hepatocarcinoma Hep G2 cells. Despite these favorable observations on
      the 3D culture with OSM, the final attained functional levels at the 5th week
      were still over ten-times lower than those of Hep G2 cells when standardized with
      a cellular DNA amount. Although further improvement is needed for the complete
      functional restoration and maturation in vitro, these results demonstrate that a
      combination of 3D culture using PLLA scaffolds and OSM offers promising culture
      conditions for in vitro maturation of human hepatocyte progenitors.

PMID- 14636013
TI  - Biomaterials in orthopedic surgery: effects of a nickel-reduced stainless steel
      on in vitro proliferation and activation of human osteoblasts.
AB  - A new austenitic stainless steel compound, P558, has been widely recognized to
      have good mechanical properties, excellent potential for corrosion resistance and
      negligible nickel ion release, making it a promising substitute for more
      expensive metallic prostheses with limited machinable features. The effect of
      P558 was studied in vitro and human osteoblast- like cells (MG63) were cultured
      directly on P558, Ti6Al4V alloy (Ti), and polystyrene (Control) for 72 hours.
      Osteoblast functions were evaluated by assaying cell proliferation and synthetic
      activity after 1.25(OH)2D3 stimulation. Results demonstrated that growth of MG63
      on P558 was not negatively affected when compared to the Ti and Control groups
      and showed no alteration in the production of ALP, NO and PICP. Moreover, IL-6
      was lower, whereas OC and TGFbeta1 were significantly higher. SEM images revealed
      that cells proliferated and differentiated on P558 without any alteration in
      their morphology. The current findings have demonstrated that P558 promotes
      osteoblast proliferation, activation and differentiation without negative effects
      and, thus, its good biocompatibility when used for orthopedic application.

PMID- 14636014
TI  - Microencapsulation and culture in vitro of rat pinealocytes.
AB  - BACKGROUND: Melatonin is a powerful anti-aging reagent for scavenging free
      radicals. However, the effect of exogenous melatonin on age-dependent diseases is
      uncertain. Immune rejection has limited xenotransplantation or
      allotransplantation of the pineal gland. The aim of this study was to assess cell
      viability and the function of rat pinealocytes encapsulated in APA capsules and
      offer experimental suggestions for pineal microencapsulation grafting to resist
      aging. METHODS: The pineal glands of neonatal rats were removed. Pinealocytes
      were isolated and encapsulated in APA microencapsulation and cultured.
      Morphological appearance of the microencapsulation was observed. Trypan blue
      staining and 5-HT immunocytochemical assay were used to detect cell viability and
      identify pinealocytes. The expression of AA-NAT mRNA was confirmed by RT-PCR.
      Melatonin release was measured and compared by HPLC. RESULTS: Both control and
      encapsulated pinealocyte cultures survived well. The majority of the encapsulated
      pinealocytes as well as unencapsulated cells remained 5-HT positive. No
      significant difference in melatonin secretion and the expression level of AA-NAT
      mRNA between encapsulated and unencapsulated pinealocytes was found. CONCLUSIONS:
      Pinealocytes survive and remain functionally competent in vitro at least 2 weeks
      after microencapsulation.

PMID- 14636015
TI  - Role of intensive PEX in a patient with fulminant hepatic failure due to Wilson's
      disease (WD) in preparation for orthotopic liver transplantation (OLT).

PMID- 14636016
TI  - What is Babesia microti?
AB  - Babesia microti (Apicomplexa: Piroplasmida) has historically been considered a
      common parasite of Holarctic rodents. However, human babesiosis due to this
      species has generally been limited to the northeastern seaboard of the United
      States and Minnesota and Wisconsin. The absence of reports of B. microti
      babesiosis from sites where the agent is enzootic, such as in western Europe,
      remains unexplained. Previous work focusing on the 18S rDNA demonstrates little
      sequence diversity among samples from allopatric host populations across a wide
      geographical area. It may be that genetic diversity is underestimated due to
      sample size or the gene analysed. Accordingly, we collected blood or spleen
      samples from American or Eurasian animals with parasites that were
      morphologically consistent with B. microti, amplified the 18S rDNA and beta
      tubulin gene, and conducted phylogenetic analysis. Surprisingly, what was
      considered to be 'B. microti' by microscopy appears to be a diverse species
      complex. We identify 3 distinct clades within this complex, including parasites
      from non-rodent hosts. Rodent parasites comprise 2 clades, one representing
      zoonotic isolates, and the other apparently maintained in microtine rodents, and
      therefore their morphological detection within animals from a site does not
      necessarily imply a risk to public health.

PMID- 14636017
TI  - Clotrimazole, ketoconazole, and clodinafop-propargyl inhibit the in vitro growth
      of Babesia bigemina and Babesia bovis (Phylum Apicomplexa).
AB  - We evaluated the growth inhibitory efficacy of the imidazole derivatives,
      clotrimazole (CLT) and ketoconazole (KC), and the herbicide clodinafop-propargyl
      (CP), in in vitro cultures of Babesia bovis and B. bigemina. Clotrimazole was
      effective in a dose range of 15 to 60 microM (IC50: 11 and 23.5 microM), followed
      by KC (50 to 100 microM; IC50: 50 and 32 microM) and CP (500 microM; IC50: 265
      and 390 microM). In transmission electron microscopy, extensive damage was
      observed in the cytoplasm of drug-treated parasites. Combinations of CLT/KC,
      CLT/CP and CLT/KC/CP acted synergistically in both parasites. In contrast, the
      combination of KC/CP was exclusively effective in B. bovis, but not in B.
      bigemina.

PMID- 14636018
TI  - A multiplex PCR assay for the simultaneous detection and discrimination of the
      seven Eimeria species that infect domestic fowl.
AB  - This study reports the development of a novel multiplex PCR assay based on SCAR
      (Sequence-Characterised Amplified Region) markers for the simultaneous diagnosis
      of the 7 Eimeria species that infect domestic fowl. Primer pairs specific for
      each species were designed in order to generate a ladder of amplification
      products ranging from 200 to 811 bp. Sensitivity tests for each species were
      carried out, showing a detection threshold of 1-5 pg, which corresponds
      approximately to 2-8 sporulated oocysts. Distinct isolates of the 7 Eimeria
      species from different geographical sources were tested and successfully detected
      by the assay. All the species were amplified homogeneously, whether or not one of
      them was present in a high quantity, indicating that there was no cross
      interference. The assay was also tested with different sources of Taq DNA
      polymerase and thermocycler models, confirming the high reproducibility of the
      reaction. The economy of consumables and labour represented by a single-tube
      reaction greatly facilitates the molecular diagnosis of a large number of
      samples, making it appropriate for field epizootiological surveys. We propose the
      use of this multiplex PCR assay as a rapid and cost-effective diagnostic method
      for the detection and discrimination of the 7 Eimeria species that infect
      domestic fowl.

PMID- 14636019
TI  - Impact of parental onchocerciasis and intensity of transmission on development
      and persistence of Onchocerca volvulus infection in offspring: an 18 year follow
      up study.
AB  - This study analysed the impact and the extent by which parental Onchocerca
      volvulus infection, intensity of transmission of O. volvulus infective 3rd-stage
      larvae (L3) and anthropometric factors may influence the acquisition, development
      and persistence of O. volvulus infection in offspring. A total of 15290
      individuals in 3939 families with 9640 children were surveyed for microfilariae
      of O. volvulus, and prevalence and level of O. volvulus infection in children
      aged 0 to 20 years from infected and non-infected parents were followed
      longitudinally for 18 years. Children from O. volvulus-infected mothers had not
      only a substantially higher risk to become infected; they also acquired infection
      earlier in life and developed higher infection levels. Multiple logistic
      regression analysis showed that maternal O. volvulus infection and children's age
      are the predominant predictors for patent O. volvulus infection, while the
      intensity of transmission, measured by the annual transmission potential (ATP) of
      O. volvulus L3, was less decisive. Longitudinal follow up of children showed that
      during vector control activities by the Onchocerciasis Control Programme (OCP)
      and in low-level transmission areas, infection persisted at higher levels in
      children from O. volvulus-positive mothers. In summary, the dominant risk factor
      for children to become infected is maternal onchocerciasis, and also age
      associated factors will strongly impact on the development of patent O. volvulus
      infection in offspring.

PMID- 14636020
TI  - Interaction of the proteasome S5a/Rpn10 multiubiquitin-binding protein and the 8
      kDa calcium-binding protein of Schistosoma mansoni.
AB  - A distinct 8 kDa calcium-binding protein (CaBP) is preferentially expressed at
      the cercarial stage during the life-cycle of the schistosome. Available data
      indicate that this CaBP may be associated with tissue/organ remodelling
      (involving protein degradation and synthesis of new proteins) during
      transformation of the cercariae from free-living form in water to parasitic life
      in the vertebrate host. Many CaBP molecules (e.g. calmodulin) show Ca(++)
      dependent interaction with target proteins and thus modulate their activity.
      Accordingly, the parasite 8 kDa CaBP was used as a probe to clone and identify
      putative target protein(s) directly by binding interaction. Screening of
      schistosome lambdagt11 expression library with radio-iodinated CaBP yielded
      several overlapping clones showing Ca(++)-dependent binding of the CaBP. Sequence
      analyses revealed that these clones encode the S5a/Rpn10 multiubiquitin-binding
      protein which is a component of the regulatory 19S subunit of the 26S proteasome.
      The schistosome molecule, designated SmS5a, is 420 amino acids long. The nearly
      full length molecule (Gln3-Ser420) as well as the amino terminal (N-S5a, Gln3
      Gly200) and carboxyl-terminal (C-S5a, Asp225-Ser420) portions were synthesized in
      bacteria, purified, and antibodies to the parasite SmS5a were prepared.
      Interaction between SmS5a and the 8 kDa CaBP in a Ca(++)-dependent manner was
      found under various experimental conditions: CaBP-Sepharose bound soluble SmS5a,
      immobilized SmS5a bound soluble CaBP, and complex formation was found when both
      molecules were in solution. Furthermore, it was shown that the C-terminal portion
      of SmS5a, but not the N-terminal portion of the molecule, reacted with the CaBP.
      SmS5a synthesized in a cell-free system and Western blots revealed 2 species,
      conceivably corresponding to the naked molecule (approximately 50 kDa) and the
      molecule subjected to post-translational modification (approximately 70 kDa). The
      present studies suggest that proteasome activity may be modulated by calcium, and
      this modulation is mediated via CaBP molecule(s).

PMID- 14636021
TI  - Specific sites in the Beta Interaction Domain of a schistosome Ca2+ channel beta
      subunit are key to its role in sensitivity to the anti-schistosomal drug
      praziquantel.
AB  - Praziquantel, the drug of choice against schistosomiasis, disrupts calcium (Ca2+)
      homeostasis in schistosomes via an unknown mechanism. Voltage-gated Ca2+ channels
      are heteromultimeric transmembrane protein complexes that contribute to impulse
      propagation and also regulate intracellular Ca2+ levels. Beta subunits modulate
      the properties of the pore-forming alpha1 subunit of high voltage-activated Ca2+
      channels. Unlike other Ca2+ channel beta subunits, which have current stimulatory
      effects, a beta subunit subtype found in S. mansoni (SmbetaA) and S. japonicum
      (Sjbeta) dramatically reduces current levels when co-expressed with Ca2+ channel
      alpha1 subunits in Xenopus oocytes. It also confers praziquantel sensitivity to
      the mammalian Cav2.3 alpha1 subunit. The Beta Interaction Domains (BIDs) of
      SmbetaA and Sjbeta lack 2 conserved serines that each constitute a consensus site
      for protein kinase C (PKC) phosphorylation. Here, we use site-directed
      mutagenesis of schistosome beta subunits to show that these unique functional
      properties are correlated with the absence of these consensus PKC sites in the
      BID. Furthermore, a second schistosome beta subunit subtype contains both serines
      in the BID, enhances currents through alpha1 subunits, and does not confer
      praziquantel sensitivity. Thus, phosphorylation sites in the BID may play
      important roles in defining the modulatory properties and pharmacological
      sensitivities of schistosome Ca2+ channel beta subunits.

PMID- 14636022
TI  - Persistent infection of Mongolian jirds with a non-pathogenic trypanosome,
      Trypanosoma (Herpetosoma) grosi.
AB  - Non-pathogenic trypanosomes of the subgenus Herpetosoma are normally host
      specific, and laboratory models include Trypanosoma lewisi in rats and
      Trypanosoma musculi in mice. Two isolates of Trypanosoma grosi, originating from
      Apodemus agrarius and Apodemus peninsulae, grew well in Mongolian jirds, Meriones
      unguiculatus, after intraperitoneal inoculation of 2 x 10(5) or a minimum 500
      bloodstream forms. The course of T. grosi infection in jirds resembled T. musculi
      infection in mice, rather than T. lewisi infection in rats. At week 2 to 3 p.i.
      trypanosomes disappeared from the bloodstream, and neither prednisolone treatment
      nor splenectomy prevented parasite elimination from the bloodstream. However,
      these treatments induced a marked increase in peak parasite counts. Regardless of
      prednisolone treatment or splenectomy, all jirds after day 21 p.i. became
      resistant to the reinfection. Although no trypanosomes were detected in the
      bloodstream of recovered jirds, dividing parasites persisted in the medullary
      capillaries of the kidney, like T. musculi infection in mice. We propose the T.
      grosi infection in jirds as an additional laboratory model for the study of non
      pathogenic trypanosomes.

PMID- 14636024
TI  - An investigation of chemotaxis in the insect parasitic nematode Heterorhabditis
      bacteriophora.
AB  - We tested the chemotactic responses of dauer juvenile stages (DJs) of the insect
      parasitic nematode Heterorhabditis bacteriophora to a variety of compounds that
      are known to be highly attractive or highly repellent to Caenorhabditis elegans.
      While H. bacteriophora DJs respond to alcohols and some aromatic compounds as
      well as to host metabolites such as uric acid and CO2, the most notable
      difference in the responses of these two nematodes is that H. bacteriophora DJs
      are unresponsive to a large number of compounds which C. elegans finds highly
      attractive. The latter compounds are typical by-products of bacterial metabolism
      and include aldehydes, esters, ketones and short-chain alcohols. While C. elegans
      finds long-chain alcohols (e.g. 1-heptanol and 1-octanol) repellent and short
      chain alcohols highly attractive, H. bacteriophora DJs are strongly attracted to
      1-heptanol, 1-octanol and 1-nonanol and find short-chain alcohols to be only
      slightly attractive. Parasitic-stage H. bacteriophora nematodes show a very weak
      chemotactic response to volatile molecules that DJs find highly attractive. Our
      results suggest that, associated with the adoption of a parasitic mode of life by
      Heterorhabditis, there was an adaptive change in chemotactic behaviour of the
      infective stages, resulting in a decreased sensitivity to volatile by-products of
      bacterial metabolism and an increased sensitivity towards long-chain alcohols and
      other insect-specific volatiles and possibly also to herbivore-induced plant
      volatiles.

PMID- 14636023
TI  - Molecular epidemiological survey on the vectors of Thelazia gulosa, Thelazia
      rhodesi and Thelazia skrjabini (Spirurida: Thelaziidae).
AB  - A Polymerase Chain Reaction (PCR)- based assay developed for the specific
      identification of Thelazia gulosa, Thelazia rhodesi and Thelazia skrjabini
      (Nematoda, Spirurida), which cause bovine ocular thelaziosis, was evaluated for
      its usefulness in detecting the intermediate hosts and in estimating the
      infection prevalence of vectors in field conditions throughout 5 years (from 1997
      to 2001). A total of 5190 flies were captured and identified as Musca larvipara,
      Musca osiris, Musca autumnalis, Musca tempestiva or Musca domestica. Genomic DNA
      was extracted from pools constituted by heads, thoraces, abdomens and wings of 10
      flies of each species, and 2076 samples were subjected to a PCR assay to
      specifically detect the ribosomal ITS-1 sequence of bovine Thelazia. Amplicons
      were sequenced and subjected to digestion with CpoI restriction enzyme. M.
      autumnalis, M. larvipara, M. osiris and M. domestica species were shown to be PCR
      positive. T. gulosa was specifically detected by PCR in M. autumnalis, M.
      larvipara, M. osiris and M. domestica, whereas T. rhodesi is in M. autumnalis and
      M. larvipara. Of 27 positive samples, 23 were positive for T. gulosa and 4 for T.
      rhodesi, with a mean prevalence of 2.86% in the whole fly population collected.
      The highest mean prevalence values of infection were detected in M. autumnalis
      (4.46%) and M. larvipara (3.21%), and the former species was confirmed to be the
      vector of T. gulosa and T. rhodesi. This study is the first report of M. osiris
      as a vector of T. gulosa and M. larvipara as a vector of T. gulosa and T. rhodesi
      under natural conditions. The occurrence of Thelazia in fly populations in the
      Apulia region of Italy (in the 5 grazing seasons considered) indicates that
      cattle thelaziosis is enzootic in southern Italy. This molecular assay should be
      a useful epidemiological tool for assessing the role of different species of
      flies as intermediate hosts of thelaziae.

PMID- 14636025
TI  - Spatial and temporal repeatability in parasite community structure of tropical
      fish hosts.
AB  - An assessment is made of the repeatability of parasite community structure in
      space for a marine fish, and in space and time for a freshwater fish from south
      eastern Mexico. The marine fish species was the red grouper, Epinephelus morio
      (collected from 9 localities), and the freshwater species was the cichlid,
      Cichlasoma urophthalmus (collected from 6 localities: including monthly at 2
      localities for 1 year, and bimonthly at 1 locality in 1990 and 1999). Pairwise
      interspecific associations and analyses of nested patterns in the distributions
      of parasite species among hosts were used in both fish species, with comparisons
      over time made only with the cichlid. Positive interspecific associations, and
      nested patterns were noted in some localities for both fish species, and/or at
      some sampling times for the cichlid fish. However, non-random patterns in the
      structure of parasite communities in these 2 host species only were observed
      sporadically. When present, nestedness in both fish species was apparently linked
      with a positive association between total infection intensities and fish size.
      Additionally, adjacent localities were more likely to display similar parasite
      community structure than distant ones. This preliminary result suggests that
      distance between localities is an important determinant of predictability in
      parasite community structure.

PMID- 14636026
TI  - Interspecific interactions between Acanthocephala in the intestine of brown
      trout: are they more frequent in Ireland?
AB  - The aim of this paper was to test the hypothesis that when the 2 species of
      Acanthocephalan Pomphorhynchus laevis and Acanthocephalus clavula are found
      concurrently within the intestine of brown trout under field conditions, they
      have the potential to interact negatively. Evidence has shown that Acanthocephala
      are more likely to exhibit negative interactions with their own and other
      species, under both field and experimental conditions. Furthermore, the
      likelihood of these interactions is increased in Ireland because of the absence
      of certain definitive hosts and the fact that concurrent infections by two or
      more species of Acanthocephala are more commonly observed in fish. Data collected
      from wild and stocked brown trout and from 2 lakes provided an opportunity to
      compare the 2 potentially interacting helminth species in their fundamental and
      realized niche and several pieces of convincing evidence are provided here to
      support the hypothesis. A significant negative association between the numbers of
      each species found in individual fish was reported and this was consistent for
      both wild and stocked trout. Furthermore, an analysis of the proportions of low,
      moderate and high intensity infections in single and concurrent infections
      revealed a significant reduction in increasing intensities in concurrent
      infections compared to single infections. Finally, strikingly different patterns
      of niche inhabitation were observed, particularly for P. laevis in the presence
      of A. clavula in wild trout. Results from the niche width analysis also support
      the observations on average position in single and concurrent infections. The
      niche width of P. laevis when it co-occurred with A. clavula decreased markedly
      in high intensity infections compared to low intensity infections.

PMID- 14636027
TI  - A reinforced random walk model of tumour angiogenesis and anti-angiogenic
      strategies.
AB  - It is now well accepted that the growth of a tumour beyond approximately 2 mm in
      diameter is dependent on its ability to induce the growth of new blood vessels, a
      process called angiogenesis. This has raised hope that an anti-angiogenic
      treatment may be effective in the fight against cancer. Here we formulate, using
      the theory of reinforced random walks, an individual cell-based mathematical
      model of tumour angiogenesis in response to a diffusible angiogenic factor. The
      early stages of angiogenesis, in which endothelial cells (EC) escape the parent
      vessel and invade the extra-cellular matrix, are included in the model, as are
      the action of a proteolytic enzyme, EC proliferation and capillary branching and
      anastomosis. The anti-angiogenic potential of angiostatin, a known inhibitor of
      angiogenesis, is also examined. The capillary networks predicted by the model are
      in qualitative agreement with experimental observations. Proteolysis and
      proliferation are shown to be crucial for vascularization, whilst angiostatin is
      seen to be capable of limiting capillary growth.

PMID- 14636028
TI  - AVM modelling by multi-branching tube flow: large flow rates and dual solutions.
AB  - Cerebral arteriovenous malformations (AVMs) present a common yet complex clinical
      challenge, through 'steal' phenomena, haemorrhage risks and epilepsy effects,
      aspects which are little understood even for individual lesions. The main
      difficulty lies in understanding the detailed haemodynamics of AVMs and
      especially the enhanced through-flow associated with steal. Mathematically, as a
      basic step, the paper investigates a nonlinear inviscid model for the planar
      incompressible flow of fluid through a branched geometry consisting of a single
      feeding mother tube which splits into two or more non-aligned daughter tubes.
      Recurrence relations between the unknown flow profiles in the daughter tubes and
      the incoming rotational flow profile in the mother tube are derived, analysed,
      and solved in detail in order to find the total flow rate. The results show
      greatly enhanced through-flow arising, for a fixed value of the total downstream
      flow area, either from non-unique solutions to the problem or more particularly
      from an increase in the number of daughter tubes, or from both, depending on the
      distribution of pressure differences applied across the branching region and the
      total downstream flow area. Extensions of the basic flow model are noted, along
      with comparisons with recent direct numerical simulations and discussion of
      possible repercussions in the context of treatment and clinical observations of
      enhanced through-flows in AVMs.

PMID- 14636029
TI  - Periodic breathing induced by arterial oxygen partial pressure oscillations.
AB  - The Grodins model of respiratory control (Grodins et al., 1967) describes cardio
      respiratory control for a lung with homogeneous gas concentrations. In this study
      we modify the Grodins model to take account of the inhomogeneities in gas
      concentration within the lung that are seen in many subjects with respiratory
      illnesses. This modification has the effect of lowering arterial oxygen partial
      pressure significantly. We investigate the effect on cardio-respiratory control
      of this low arterial oxygen signal and find that the governing equations may be
      reduced to a single delay-differential equation. This reduced model is found to
      be a good approximation to the full model and gives predictions that are similar
      to reported clinical data.

PMID- 14636030
TI  - Diabetes mellitus and pharmacological therapy.
AB  - Diabetes mellitus can be a devastating lifelong disease if not treated
      appropriately. The physician and the patient should be aware of both extremes
      involved with DM: hyperglycemia and hypoglycemia. Patient education and
      preventive care are perhaps more important in this disease than many others. A
      multidisciplinary approach involving the patient, physician, and diabetic
      educator is best to assure a better quality of life. Enormous advances in the
      treatment of diabetes have occurred over the past decade and even greater ones
      can be expected in the future. New drugs, insulin delivery devices, and
      noninvasive glucose monitoring machines have the potential to normalize blood
      sugar levels and return diabetics to a near normal lifespan without
      complications.

PMID- 14636031
TI  - Diabetic foot infections and antibiotic therapy.
AB  - Diabetic foot infections are associated with high morbidity and mortality rates
      as well as significant financial impact on the health care system. Improved
      patient outcomes and intelligent use of resources should determine the selection
      of diagnostic procedures and the therapeutic modalities used. Diabetic patients
      who develop lower extremity infections require a multidisciplinary approach in
      the management of their infections and other disorders. Aggressive surgical
      debridement and appropriate and adequate antibiotic therapy are necessary to
      successfully treat severe foot infections and permit faster recovery.

PMID- 14636032
TI  - Medical evaluation and treatment of diabetic peripheral neuropathy.
AB  - Diabetes mellitus is a major health concern that is only expected to become more
      prevalent over the next few decades. It causes much morbidity and mortality
      through various macro- and microvascular complications, including diabetic
      neuropathy. Currently, there is no treatment that directly affects the natural
      course of diabetic neuropathy except for rigorous glycemic control, a goal that
      is not always achievable. Despite these therapeutic limitations, the morbidity
      caused by diabetic neuropathy can be minimized by early and accurate diagnosis. A
      detailed history and physical examination, along with carefully selected
      laboratory tests will confirm the presence of diabetic neuropathy while excluding
      other etiologies that may require alternative management strategies. Treatment is
      always tailored to the patient's symptoms. In addition to improved glycemic
      control, health care providers can provide education, support, and symptomatic
      relief. There are many pain modulating therapies that are effective in diabetic
      neuropathy as discussed above. Nortriptyline at low doses is an inexpensive well
      tolerated medication that is effective. Gabapentin is an excellent choice when
      nortriptyline is ineffective or not tolerated. Other anticonvulsants, such as
      lamotrigine, carbamazepine, oxycarbazepine, and topiramate, may also provide
      benefit. Judicious use of narcotics is appropriate when other treatment
      modalities fail. The importance of treating underlying depression cannot be
      overemphasized. When gait becomes impaired as a result of neuropathy, appropriate
      prescription of assistive devices will prevent injuries from falls. Ankle-foot
      orthoses and other orthotic devices may allow patients to remain ambulatory and
      independent for a longer period. Despite the challenges ahead, the future holds
      the promise of more effective treatments for diabetes mellitus and its
      complications.

PMID- 14636033
TI  - Vascular evaluation and arterial reconstruction of the diabetic foot.
AB  - Findings of diminished or absent pulses, pallor on elevation, redness of the foot
      on lowering of the leg, sluggish refilling of the toe capillaries, and thickened
      nails or absence of toe hair are consistent with impaired arterial perfusion to
      the foot. When ischemia is recognized as contributing to pedal ulceration and
      infection in the diabetic foot, quantitation of its severity may be difficult.
      Standard clinical evaluation of trophic changes is limited in an infected foot
      with its accompanying swelling, edema, and erythema. A palpable pedal pulse does
      not preclude the possibility of the presence of limb-threatening ischemia.
      Additional non-invasive vascular studies should be undertaken for these patients.
      Management of the diabetic foot is often a complex clinical problem. However, the
      principles of care are simple, including correction of systemic factors, such as
      blood glucose control, cardiovascular risk factor management, and smoking, as
      well as local factor correction, such as debridement, pressure relief, infection
      control, and revascularization when indicated. When a patient presents with
      evidence of infection, adequate drainage and antibiotic therapy are mandatory.
      The next step should be performed to differentiate the more common neuropathic
      ulcerations from the truly ischemic ulceration. Symptoms of rest pain or
      claudication are not often helpful because many of these patients are
      asymptomatic as a result of the presence of their neuropathy and inactivity. If
      an infected foot requires debridement or open partial forefoot amputation,
      observing the wound on a daily base is also important. Once infection is
      eradicated, there should be prompt signs of healing, including the development of
      wound granulation within several days. If wounds are not showing signs of prompt
      healing, arteriography is necessary. Early aggressive drainage, debridement, and
      local foot amputations combined with liberal use of revascularization results in
      cumulative limb salvage of 74% at 5 years in high-risk groups. Others report that
      pedal bypass to the ischemic infected foot is effective and safe as long as
      infection adequately controlled. These studies strongly suggest that early
      recognition and aggressive surgical drainage of pedal sepsis followed by surgical
      revascularization is critical to achieving maximal limb salvage in the high-risk
      population. Patients who have diabetes present a unique challenge in lower
      extremity revascularization because of the distal origination of many bypasses,
      distal distribution of the occlusive disease, and the frequently calcified
      arterial wall. An aggressive multidisciplinary approach to foot disease
      associated with diabetes involving the primary care provider, medical
      specialists, interventional radiology, and podiatric, plastic, and vascular
      surgeons will provide optimal medical and surgical care. Peripheral vascular
      disease is highly treatable if intervention is instituted in a timely and
      collegial fashion.

PMID- 14636034
TI  - Diabetic foot ulcerations: management and adjunctive therapy.
AB  - Foot ulcerations, infections, gangrene, and lower extremity amputation are major
      causes of disability to the patient who has diabetes mellitus, often resulting in
      significant morbidity, extensive periods of hospitalization, and mortality.
      Although not all such lesions can be prevented, it is possible to dramatically
      reduce their incidence through appropriate management and prevention protocols
      incorporating a multidisciplinary team approach.

PMID- 14636035
TI  - Imaging modalities of the diabetic foot.
AB  - Charcot osteoarthropathy is a devastating process that occurs in the diabetic
      foot. It must be distinguished from other conditions, such as osteomyelitis, with
      efficiency and accuracy. The prognosis and treatment depends on it. Charcot
      progresses along four radiographically identifiable stages; therefore, plain
      films should be the first step in the evaluation. When osteomyelitis is
      suspected, a three-phase bone scan may allow clear enough anatomic detail to
      diagnosis bony involvement compared with soft tissue in the forefoot. In the
      midfoot, a three-phase bone scan alone is not specific enough to distinguish
      between Charcot and osteomyelitis. Enhancing the bone scans by adding an
      additional phase (four-phase) or tracer (gallium) does not appear to improve
      specificity significantly. Computerized bone flow studies may be more helpful in
      making the distinction, particularly in acute presentation. A CT scan is not
      indicated because the MR image will better define the anatomic extent of the
      process for preoperative planning. The combined WBC scans and sulfur colloid
      marrow scans show improved specificity and can distinguish between Charcot and
      osteomyelitis. Combined leukocyte scan with bone marrow imaging is superior to
      leukocyte and bone scan alone or in combination for detecting infection in the
      neuropathic foot. The combined leukocyte scan and bone marrow imaging is the
      current gold standard for evaluating the presence of diabetic foot infection
      versus osteoarthropathy, and MR imagine is the anatomic gold standard that may be
      used to define the extent of the process.

PMID- 14636036
TI  - External fixation in the management of Charcot neuroarthropathy.
AB  - Charcot neuroarthropathy is a complex sequela of neuropathies associated with
      diabetes mellitus, syringomyelia, alcoholism, and other disorders. The treatment
      of deformities associated with Charcot neuroarthropathy is evolving from a
      passive approach to one in which an earlier recognition of the emergence of the
      event permits an avoidance of deformity. As the understanding of the etiology and
      natural history of Charcot neuroarthropathy deepens, it has become apparent that
      many of the deformities that do develop may be reconstructed expeditiously by the
      surgeon with a thorough understanding of the diabetic foot and experience in the
      use of external fixation.

PMID- 14636037
TI  - Soft tissue reconstruction of the diabetic foot.
AB  - Treatment of wounds in the diabetic foot presents a set of difficult problems
      that requires "out of the box" thinking. The traditional approach of off-loading
      these wounds is often expensive, time-consuming, and in some cases seemingly
      never ending. The literature speaks loudly for a change in the philosophy of
      treating chronic wounds. When developing a team to treat chronic diabetic wounds,
      a reconstructive foot and ankle surgeon trained in these techniques is an
      appropriate addition to the team.

PMID- 14636038
TI  - Elective surgery of the diabetic foot.
AB  - It has been clearly demonstrated that elective surgery can be performed in the
      neuropathic foot. If infection is controlled and arterial supply is adequate,
      limb salvage can be greatly enhanced with an aggressive approach to elective
      procedures in the patient who has diabetes.

PMID- 14636039
TI  - Amputation considerations and energy expenditures in the diabetic patient.
AB  - Amputations are not procedures of choice but are often necessary and valuable
      tools for returning a patient to a more active lifestyle. Because of the
      comorbidities associated with diabetes, this is an important consideration. A
      return to a more active existence can reduce the effect of vascular disease,
      hyperglycemic states, and functional limitations. It is an interesting and not
      uncommon occurrence for the chronic wound patient, when offered an amputation, to
      have the procedure because the frequency of needed medical care has stripped him
      of his independence. The frequency of wound care in the nonhealing wound and its
      personal demands can be compared with the demands placed on the dialysis patient.
      The greatest obstacle for the uninitiated surgeon is a sense of hesitancy: Am I
      moving too fast to amputation as an answer? The ability to make this decision
      comes with experience and with prioritizing the patient's needs. Life-threatening
      infections and avascular extremities that are not bypassable are the easier
      decisions to make, as there is little choice at that point. In deciding whether
      to amputate, the wise surgeon will take into consideration the medical and
      mobility needs of each patient and determine level and timing based on
      understanding of the whole person.

PMID- 14636040
TI  - Implication of virulence factors in Escherichia coil O157:H7 pathogenesis.
AB  - Since the first documented outbreak of hemorrhagic colitis caused by Escherichia
      coli O157:H7 in 1982, numerous publications have demonstrated or proposed
      putative components implicated in the pathogenesis of this gastrointestinal
      infection. Indeed, Escherichia coli O157:H7 pathogenesis is linked to several
      potential virulent factors such as verotoxins (or Shiga-like toxins), components
      implicated in attaching/effacing of microvilli, and the enterohemolysin
      phenotypes. Defining the precise molecular mechanisms involved in the
      pathogenesis of E. coli O157:H7 implies detailed comprehension of the virulent
      factors that provoke a wide range of pathophysiological symptoms. The public
      health significance of this emerging world-wide menace has been demonstrated by
      clinical complications during treatment, its low infectious dose, and the
      severity of clinical manifestations. In this review I describe current knowledge
      of Escherichia coli O157:H7 pathogenesis with emphasis on known and potential
      virulent factors.

PMID- 14636041
TI  - How far have we reached in tuberculosis vaccine development?
AB  - Tuberculosis, a bacterial disease prevalent since ancient times, continues to
      cause the most deaths globally compared with all other diseases. The causative
      agent Mycobacterium tuberculosis is responsible for different types of
      tuberculosis in humans; however, pulmonary tuberculosis is the most common and
      causes the most deaths. Mycobacterium tuberculosis is an intracellular pathogenic
      bacterium, which has developed sophisticated mechanisms to survive inside host
      mononuclear phagocytes and thus evade the host immune system. This is attributed
      primarily to an inadequate immune response toward infecting bacteria, which
      results in temporary growth inhibition rather than death and subsequently allows
      the bacteria to multiply immensely, leading to full-blown disease in an
      individual. This disease has become a challenge due to poor diagnosis, a low
      efficiency tuberculosis vaccine (Mycobacterium bovis Bacillus Calmette-Guerin
      [BCG]), a long-term antibacterial chemotherapy regimen (approximately 6 months),
      and an emergence of multiple drug resistant strains of Mycobacterium tuberculosis
      especially in people with human immune deficiency virus (HIV) infection, for whom
      researchers worldwide must develop effective short-term chemotherapy and an
      effective vaccine. In this review different aspects of vaccines in tuberculosis
      are discussed, and these include the traditional BCG vaccine, the modern
      auxotrophic vaccine, the subunit or acellular vaccine; and a DNA vaccine. We
      discuss also the potential of mycobacterial lipids as a vaccine or as an adjuvant
      in the future. Since complete genome information of Mycobacterium tuberculosis
      H37Rv and bioinformatics tools are available, it is possible to develop new
      strategies for a better and effective tuberculosis vaccine, which can replace the
      traditional BCG vaccine.

PMID- 14636042
TI  - T cell immunity to brucellosis.
AB  - Brucellosis is an ancient disease of animals and man that still threatens the
      health and prosperity of many, primarily in the third world, who depend on animal
      agriculture for their livelihood. Further, its pathogenicity and the facts that
      it is zoonotic is effectively eradicated from many Western nations make it a
      dangerous bioterrorism threat. Targeted human vaccination may reduce the various
      threats brucellosis poses. Significant effort has been expended toward this goal
      and many candidate vaccines exist. However, the ideal vaccine would be a subunit
      vaccine that specifically targets only the critical aspects of the immune
      response necessary to induce immunity. Much about the immune response, in
      particular the T cell response, remains to be discovered in order to accomplish
      that goal. In this review we focus on T cell responses to brucellosis with
      particular attention to the specific roles of T cell subtypes. We also point out
      areas of research on T cell responses that may allow exploitation of cutting edge
      vaccine technologies for the next generation vaccine for brucellosis.

PMID- 14636043
TI  - Protective immunity of pneumococcal glycoconjugates.
AB  - Pneumococcal polysaccharides (PSs), designated as T-cell independent type 2 (TI
      2) antigens, induce poor immune responses in young children. Splenic marginal
      zone B cells, associated with CD21, CD19 and C3d, play an important role in TI-2
      antibody responses, and provide host defense against bacterial pathogens.
      Antibody response, avidity, and opsonophagocytic activity of antisera were
      examined in mice immunized with type 9V PS conjugated to inactivated pneulmolysin
      (Ply) or to autolysin (Aly). Compared to mice given 9V PS alone, serum IgG and
      IgM concentrations against the 9V PS were higher in mice immunized with
      conjugates. High concentrations of serum antibodies were maintained for over 12
      weeks. The relative avidities of IgG and IgM antibodies and opsonophagocytic
      activity against 9V pneumococci were high in mice immunized with conjugates.
      Thus, conjugate vaccines can induce high as well as long duration of antibody
      response and effective functional activity. In another study, mice received
      intranasal immunization with type 9V conjugate or 9V PS. These animals produced
      9V PS IgG and IgA antibodies in their serum, spleen, intestine, lung, Peyer's
      patch and fecal extract samples. Mice immunized with these glycoconjugates
      exhibited opsonophagocytic activity and rapid bacterial clearance from blood and
      provided homologous and cross-protection against challenge with virulent
      pneumococci. These results indicate that intranasal immunization with
      glycoconjugate vaccines may serve as an alternative and convenient approach for
      prevention of pneumococcal infection.

PMID- 14636044
TI  - Helicobacter pylori and coronary heart disease: which directions for future
      studies?
AB  - Classical risk factors explain the pathogenesis of coronary heart disease (CHD)
      in only a proportion of cases; therefore, the need to investigate the possible
      role of "new" agents has incited intense research. Since 1994, a number of
      studies regarding the possible involvement of Helicobacter pylori (H. pylori)
      have been published with conflicting results. Establishing a causal link between
      this infection and CHD would be of major public health importance, since the
      eradication of the bacterium is easy and much less expensive than long-term
      treatment of the other risk factors. The main cause of this discordance was the
      vast heterogeneity of such studies: sufficiently powerful design was found only
      in few investigations, CHD was defined with a low degree of homogeneity, biases
      were obvious in the control groups, thus giving room for large variation in the
      adjustment of potential confounding factors. The present paper attempts to
      highlight the future directions towards which research should be headed in this
      area to establish a causal role of H. pylori infection in the pathogenesis of
      CHD. Future research should take three directions: 1) prospective population
      based studies in which the incidence or the recurrence of CHD be evaluated in
      correlation with H. pylori status, 2) intervention trials, focusing separately on
      the chronic and acute phases of coronary heart disease and, 3) studies of
      physiopathology (both in the animal model and humans) to understand the potential
      biological plausibility.

PMID- 14636045
TI  - Penetratin and related cell-penetrating cationic peptides can translocate across
      lipid bilayers in the presence of a transbilayer potential.
AB  - Fluorescent-labeled derivatives of the Antennapedia-derived cell-penetating
      peptide penetratin, and of the simpler but similarly charged peptides R(6)GC
      NH(2) and K(6)GC-NH(2), are shown to be able to translocate into large
      unilamellar lipid vesicles in the presence of a transbilayer potential (inside
      negative). Vesicles with diverse lipid compositions, and combining physiological
      proportions of neutral and anionic lipids, are able to support substantial
      potential-dependent uptake of all three cationic peptides. The efficiency of
      peptide uptake under these conditions is strongly modulated by the vesicle lipid
      composition, in a manner that suggests that more than one mechanism of peptide
      uptake may operate in different systems. Remarkably, peptide uptake is
      accompanied by only minor perturbations of the overall barrier function of the
      lipid bilayer, as assessed by assays of vesicle leakiness under the same
      conditions. Fluorescence microscopy of living CV-1 and HeLa cells incubated with
      the labeled peptides shows that the peptides accumulate in peripheral vesicular
      structures at early times of incubation, consistent with an initial endosomal
      localization as recently reported, but gradually accumulate in the cytoplasm and
      nucleus during more extended incubations (several hours). Our findings indicate
      that these relatively hydrophilic, polybasic cell-penetrating peptides can
      translocate through lipid bilayers by a potential- and composition-dependent
      pathway that causes only minimal perturbation to the overall integrity and
      barrier function of the bilayer.

PMID- 14636046
TI  - Interaction of ferredoxin:NADP+ oxidoreductase with phycobilisomes and
      phycobilisome substructures of the cyanobacterium Synechococcus sp. strain PCC
      7002.
AB  - The enzyme ferredoxin-NADP(+) oxidoreductase (FNR) from Synechococcus sp. PCC
      7002 has an extended structure comprising three domains (FNR-3D) (Schluchter, W.
      M., and Bryant, D. A. (1992) Biochemistry 31, 3092-3102). Phycobilisome (PBS)
      preparations from wild-type cells contained from 1.0 to 1.6 molecules of FNR-3D
      per PBS, with an average value of 1.3 FNR per PBS. A maximum of two FNR-3D
      molecules could be specifically bound to wild-type PBS via the N-terminal, CpcD
      like domain of the enzyme when exogenous recombinant FNR-3D (rFNR-3D) was added.
      To localize the enzyme within the PBS, the interaction of PBS and their
      substructures with rFNR-3D was further investigated. The binding affinity of rFNR
      3D for phycocyanin (PC) hexamers, which contained a 22-kDa proteolytic fragment
      derived from CpcG, the L(RC)(27) linker polypeptide, was higher than its affinity
      for PC hexamers containing no linker protein. PBS from a cpcD3 mutant, which
      lacks the 9-kDa, PC-associated rod linker, incorporated up to six rFNR-3D
      molecules per PBS. PBS of a cpcC mutant, which has peripheral rods that contain
      single PC hexamers, also incorporated up to six rFNR-3D molecules per PBS. Direct
      competition binding experiments showed that PBS from the cpcD3 mutant bound more
      enzyme than PBS from the cpcC mutant. These observations support the hypothesis
      that the enzyme binds preferentially to the distal ends of the peripheral rods of
      the PBS. These data also show that the relative affinity order of the PC
      complexes for FNR-3D is as follows: (alpha(PC)beta(PC))(6)-L(R)(33) >
      (alpha(PC)beta(PC))(6)-L(RC)(27) > (alpha(PC)beta(PC))(6). The data suggest that,
      during the assembly of the PBS, FNR-3D could be displaced to the periphery
      according to its relative binding affinity for different PC subcomplexes. Thus,
      FNR-3D would not interfere with the light absorption and energy transfer
      properties of PC in the peripheral rods of the PBS. The implications of this
      localization of FNR within the PBS with respect to its function in cyanobacteria
      are discussed.

PMID- 14636047
TI  - Comparison of kifunensine and 1-deoxymannojirimycin binding to class I and II
      alpha-mannosidases demonstrates different saccharide distortions in inverting and
      retaining catalytic mechanisms.
AB  - Mannosidases are key enzymes in the eukaryotic N-glycosylation pathway. These
      enzymes fall into two broad classes (I and II) and are characteristically
      different in catalytic mechanism, sequence, and structure. Kifunensine is an
      alkaloid that is a strong inhibitor against class I alpha-mannosidases but is
      only a weak inhibitor against class II alpha-mannosidases. In this paper, the
      1.80 A resolution crystal structure of kifunensine bound to Drosophila
      melanogaster Golgi alpha-mannosidase II (dGMII) is presented. Kifunensine adopts
      a (1,4)B boat conformation in the class II dGMII, which contrasts the (1)C(4)
      chair conformation seen in class I human endoplasmic reticulum alpha1,2
      mannosidase (hERMI, PDB ). The observed conformations are higher in
      conformational energy than the global minimum (4)C(1) conformation, although the
      conformation in hERMI is closer to the minimum, as supported by an energy
      calculation. Differing conformations of 1-deoxymannojirimycin were also observed:
      a (4)C(1) and (1)C(4) conformation in dGMII and hERMI, respectively. Thus, these
      two alpha-mannosidase classes distort these inhibitors in distinct manners. This
      is likely indicative of the binding characteristics of the two different
      catalytic mechanisms of these enzymes.

PMID- 14636048
TI  - Nuclear magnetic resonance-based dissection of a glycosyltransferase specificity
      for the mucin MUC1 tandem repeat.
AB  - The human glycoprotein MUC1 mucin plays a critical role in cancer progression.
      Breast, ovarian, and colon cancer cells often display unique cell-surface
      antigens corresponding to aberrantly glycosylated forms of the MUC1 tandem
      repeat. In this report, (15)N- and (13)C-labeled forms of a recombinant MUC1
      construct containing five tandem repeats were used as substrates to define the
      order and kinetics of addition of N-acetylgalactosamine (GalNAc) moieties by a
      recombinant active form of the human enzyme UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase I (ppGalNAc-T1; residues 40-559). Heteronuclear
      NMR experiments were performed to assign resonances associated with the two
      serines (Ser5 and Ser15) and three threonines (Thr6, Thr14, and Thr19) present in
      the 20-residue long MUC1 repeat. The kinetics and order of addition of GalNAc
      moieties (Tn antigen) on the MUC1 construct by human ppGalNAc-T1 were
      subsequently dissected by NMR spectroscopy. Threonine 14 was shown to be rapidly
      glycosylated by ppGalNAc-T1 with an initial rate of 25 microM/min, followed by
      Thr6 (8.6 microM/min). The enzyme also modified Ser5 at a slower rate (1.7
      microM/min), an event that started only after the glycosylation of Thr14 and Thr6
      side chains was mostly completed. Ser15 and Thr19 remained unglycosylated by
      ppGalNAc-T1. Corresponding O-glycosylation sites within all five tandem repeats
      were simultaneously modified by ppGalNAc-T1, suggesting that each repeat behaves
      as an independent substrate unit. This study demonstrated that the hydroxyl
      oxygens of Thr14 and to a lesser extent Thr 6 represent the two dominant
      substrates modified by ppGalNAc-T1 within the context of a complex MUC1 peptide
      substrate. More importantly, the availability of defined isotopically labelled
      MUC1 glycopeptide substrates and the relative simplicity of their NMR spectra
      will facilitate the analysis of other transferases within the O-glycosylation
      pathways and the rational design of tumor-associated MUC1 antigens.

PMID- 14636049
TI  - Analysis of the role of the active site residue Arg98 in the flavoprotein
      tryptophan 2-monooxygenase, a member of the L-amino oxidase family.
AB  - The flavoprotein tryptophan 2-monooxygenase catalyzes the oxidative
      decarboxylation of tryptophan to indoleacetamide. We have previously identified
      tryptophan 2-monooxygenase as a homologue of L-amino acid oxidase [Sobrado, P.,
      and Fitzpatrick, P. F. (2002) Arch. Biochem. Biophys. 402, 24-30]. On the basis
      of the sequence comparisons of the different LAAO family members, Arg98 of
      tryptophan 2-monooxygenase can be identified as an active site residue which
      interacts with the carboxylate of the amino acid substrate. The catalytic
      properties of R98K and R98A tryptophan 2-monooxygenase have been characterized to
      evaluate the role of this residue. Mutation of Arg98 to lysine decreases the
      first-order rate constant for flavin reduction by 180-fold and the second-order
      rate constant for flavin oxidation by 26-fold, has no significant effect on the
      K(d) value for tryptophan or the K(i) value for the competitive inhibitor
      indoleacetamide, and increases the K(i) value for indolepyruvate less than 2
      fold. Mutation of this residue to alanine decreases the rate constants for
      reduction and oxidation an additional 5- and 2-fold, respectively, and increases
      the K(d) value for tryptophan and the K(i) value for indolepyruvate by 31- and 17
      fold, respectively, while having an only 2-fold effect on the K(i) value for
      indoleacetamide. Both mutations increase the value of the primary deuterium
      isotope effect with tryptophan as a substrate, consistent with a later transition
      state. Both mutant enzymes catalyze a simple oxidase reaction, producing
      indolepyruvate and hydrogen peroxide. The pH dependences of the V/K(trp) values
      for the mutant enzymes show that the anionic form of the substrate is preferred
      but that the zwitterionic form is a substrate. The results are consistent with
      the interaction between Arg98 and the carboxylate of the amino acid substrate
      being critical for correct positioning of the substrate in the active site for
      efficient catalysis.

PMID- 14636050
TI  - Identification of Tyr413 as an active site residue in the flavoprotein tryptophan
      2-monooxygenase and analysis of its contribution to catalysis.
AB  - The flavoenzyme tryptophan 2-monooxygenase catalyzes the oxidation of tryptophan
      to indoleacetamide, carbon dioxide, and water. The enzyme is a homologue of l
      amino acid oxidase. In the structure of l-amino acid oxidase complexed with
      aminobenzoate, Tyr372 hydrogen bonds with the carboxylate of the inhibitor in the
      active site. All 10 conserved tyrosine residues in tryptophan 2-monooxygenase
      were mutated to phenylalanine; steady state kinetic characterization of the
      purified proteins identified Tyr413 as the residue homologous to Tyr372 of l
      amino acid oxidase. Y413F and Y413A tryptophan 2-monooxygenase were characterized
      more completely with tryptophan as the substrate to probe the contribution of
      this residue to catalysis. Mutation of Tyr413 to phenylalanine results in a
      decrease in the value of the first-order rate constant for reduction of 35-fold
      and a decrease in the rate constant for oxidation of 11-fold. Mutation to alanine
      decreases the rate constant for reduction by 200-fold and that for oxidation by
      33-fold. Both mutations increase the K(d) value for tryptophan and the K(i)
      values for the competitive inhibitors indoleacetamide and indole pyruvate by 5-10
      fold. Both mutations convert the enzyme to an oxidase, in that the products of
      the catalytic reactions of both are indolepyruvate and hydrogen peroxide. The
      V/K(trp)-pH profiles for the Tyr413 mutant enzymes no longer show the pK(a) value
      of 9.9 seen in that for the wild-type enzyme, allowing identification of Tyr413
      as the active site residue in the wild-type enzyme which must be protonated for
      catalysis. Substitution of Tyr413 abolishes the formation of the long wavelength
      charge transfer species observed in the wild-type enzyme. The data are consistent
      with the main role of Tyr413 being to maintain the correct orientation of
      tryptophan for effective hydride transfer and imino acid decarboxylation.

PMID- 14636051
TI  - Solution structure of RicC3, a 2S albumin storage protein from Ricinus communis.
AB  - The three-dimensional structure in aqueous solution of recombinant (15)N labeled
      RicC3, a 2S albumin protein from the seeds of castor bean (Ricinus communis), has
      been determined by NMR methods. The computed structures were based on 1564 upper
      limit distance constraints derived from NOE cross-correlation intensities
      measured in the 2D-NOESY and 3D-HSQC-NOESY experiments, 70 phi torsion angle
      constraints obtained from (3)J(HNH)(alpha) couplings measured in the HNHA
      experiment, and 30 psi torsion angle constraints derived from
      (3)J(H)(alpha)(Ni+1) couplings measured in the HNHB experiment. The computed
      structures showed a RMSD radius of 0.64 A for the structural core. The resulting
      structure consists of five amphipatic helices arranged in a right-handed super
      helix, a folding motif first observed in nonspecific lipid transfer proteins.
      Different than the latter, RicC3 does have not an internal cavity, a fact that
      can be related to the exchange in the pairing of disulfide bridges in the
      segment.CXC. Previous attempts to determine high resolution structures of a 2S
      albumin protein by either X-ray crystallography or NMR methods failed because of
      the heterogeneity of the protein prepared from natural sources. Both 2S albumins
      and nonspecific lipid transfer proteins belong to the prolamine superfamily, some
      of whose members are food allergens. The solution structure for recombinant RicC3
      determined here is a suitable representative structure for the broad family of
      seed 2S albumin proteins, which may help to establish meaningful relationships
      between structure and allergenicity. RicC3 is also the peptidic component of the
      immunomodulator Inmunoferon, a widely used pharmaceutical product, and its
      structure is expected to help understand its pharmaceutical activity.

PMID- 14636052
TI  - Quaternary structure and catalytic activity of the Escherichia coli ribonuclease
      E amino-terminal catalytic domain.
AB  - RNase E is an essential endoribonuclease that plays a central role in the
      processing and degradation of RNA in Escherichia coli and other bacteria. Most
      endoribonucleases have been shown to act distributively; however, Feng et al.
      [(2002) Proc. Natl. Acad. Sci. U.S.A. 99, 14746-14751] have recently found that
      RNase E acts via a scanning mechanism. A structural explanation for the
      processivity of RNase E is provided here, with our finding that the conserved
      catalytic domain of E. coli RNase E forms a homotetramer. Nondissociating
      nanoflow-electrospray mass spectrometry suggests that the tetramer binds up to
      four molecules of a specific substrate RNA analogue. The tetrameric assembly of
      the N-terminal domain of RNase E is consistent with crystallographic analyses,
      which indicate that the tetramer possesses approximate D(2) dihedral symmetry.
      Using X-ray solution scattering data and symmetry restraints, a solution shape is
      calculated for the tetramer. This shape, together with limited proteolysis data,
      suggests that the S1-RNA binding domains of RNase E lie on the periphery of the
      tetramer. These observations have implications for the structure and function of
      the RNase E/RNase G ribonuclease family and for the assembly of the E. coli RNA
      degradosome, in which RNase E is the central component.

PMID- 14636053
TI  - Increased rigidity of eglin c at acidic pH: evidence from NMR spin relaxation and
      MD simulations.
AB  - To gain physical insights into how proteins respond to changes in pH, the
      picosecond to nanosecond time scale dynamics of the small serine protease
      inhibitor eglin c have been studied by NMR spin relaxation experiments and MD
      simulations under two pH solution conditions, pH 7 and 3. Like many proteins,
      eglin c is destabilized by a lowering of the pH, although it retains enough
      stability to maintain its native conformation at pH 3. Backbone (15)N relaxation
      results show comparable global tumbling times (tau(m)) and model-free order
      parameters (S(2)) under the two pH conditions, indicating that the molecule
      maintains its overall molecular shape and structure at low pH, although the
      backbone rigidity is slightly increased (<DeltaS(pH3-pH7)(2)>/<S(2)> = 0.6%). In
      contrast, the side-chain methyl dynamics, as measured from (2)H relaxation
      experiments, show a substantial increase in rigidity at lower pH
      (<DeltaS(axis,pH3-pH7)(2)>/<S(axis)(2)> = 14.8%). Molecular dynamics simulations
      performed at these pH states produce results consistent with NMR measurements,
      showing that the two methods are in qualitative agreement. Although a full
      accounting of the physical basis for the concurrent conformational rigidification
      and destabilization at low pH requires further investigation, the high level of
      detail in the MD simulations provides a potential molecular mechanism: the
      breaking of the hydrogen bond between the side chains of Asp46 and Arg53, and
      changes in electrostatic interactions, appear to allow the binding loop to move
      closer to the core part of the protein, resulting in a more compact structure at
      low pH. This more compact structure may be responsible for the increased level of
      restriction of molecular motion. As these findings show, the stability of a
      molecular structure is distinct from its conformational rigidity, and the two can
      even change in opposite directions, against naive expectation.

PMID- 14636054
TI  - Near native structure in an RNA collapsed state.
AB  - Many large RNAs form conformationally collapsed, but non-native, states prior to
      folding to the native state or assembling with protein cofactors. Although RNA
      collapsed states play fundamental roles in RNA folding and ribonucleoprotein
      assembly processes, their structures have been poorly understood. We obtained 12
      high-quality structural constraints for the collapsed state formed by the
      catalytic core of the bI5 intron RNA using site-specific cross-linking mediated
      by a short-lived reactant. RNA tertiary structures in the collapsed and native
      states are indistinguishable, even though only the native state forms a solvent
      inaccessible core. Thus, structural neighbors in the collapsed state, including
      several long-range tertiary interactions, are approximately as close in space as
      in the native state, but RNA packing is sufficiently loose or dynamic to allow
      access by solvent. Binding by the obligate CBP2 protein cofactor has almost no
      effect on structural neighbors reported by cross-linking, even though protein
      binding chases the RNA from the collapsed state to the native state. Protein
      binding thus appears to promote only the final few angstroms of RNA folding
      rather than mediate global conformational rearrangements in the catalytic core.
      The bI5 RNA collapsed state functions to self-chaperone ribonucleoprotein
      assembly because this conformationally restrained structure lies very near that
      of the native state and excludes structures that otherwise misassemble
      efficiently.

PMID- 14636055
TI  - Structural flexibility and the thermodynamics of helix exchange constrain
      attenuation and allosteric activation of hammerhead ribozyme TRAPs.
AB  - Perturbations of precleavage equilibria in RNA-cleaving ribozymes can be
      exploited to control cleavage kinetics. In the targeted ribozyme-attenuated
      probes (TRAP) design, antisense and attenuator sequences are appended onto the
      catalytic core of a ribozyme or deoxyribozyme. The attenuator anneals to
      conserved bases in the catalytic core to form an inactive conformation, which is
      activated upon binding of a sense strand oligonucleotide to the antisense module.
      In this work, the apparent Michaelis-Menton constant (K'm) for the binding of the
      RNA substrate to the ribozyme is shown to be within a factor of 2 for a number of
      constructs whose observed cleavage rates varied by several 100-fold. These
      observations rule out models of allosteric regulation based on modulation of
      substrate binding affinity, instead favoring a model in which regulation arises
      from equilibration between the active and inactive conformations of the TRAP.
      Free energies of formation for isolated helices that are exchanged during this
      reequilibration were determined from the concentration dependence of optical melt
      data. These values established that the thermodynamic stabilities of sense
      antisense duplexes and of the attenuator-core duplexes correlate with observed
      rates of cleavage. Notably reduced cleavage rates are observed for TRAP ribozymes
      with extended antisense sequences, suggesting that tight binding of attenuator to
      the core is assisted by a long antisense portion. A construct with a 25
      nucleotide antisense showed greater than 730-fold activation upon annealing with
      a 20-nucleotide DNA sense strand oligo, representing the greatest activation
      observed to date for the TRAP design.

PMID- 14636057
TI  - Role of an N-terminal loop in the secondary structural change of photoactive
      yellow protein.
AB  - Photoactive yellow protein (PYP) is photoconverted to its putative active form
      (PYP(M)) with global conformational change(s). The changes in the secondary
      structure were studied by far-UV circular dichroism (CD) and Fourier transform
      infrared (FTIR) spectroscopy using PYP, which lacks N-terminal 6, 15, or 23 amino
      acid residues (T6, T15, and T23, respectively). Irradiation of truncated PYPs
      induced the loss of the CD signal, where the maximal difference was located at
      222 nm. The reduction of the CD signal was significantly larger than the
      calculated CD of the N-terminal helices, indicating that it is mainly accounted
      for by the unfolding and/or structural change of the helices located outside the
      N-terminal region. The difference FTIR spectra between dark and photosteady
      states recorded using the solution samples demonstrated that large absorbance
      changes in the amide mode of the beta-sheet were reduced and downshifted by
      truncation. The structural change of the beta-sheet is therefore closely
      correlated with the N-terminal loop. NaCl decelerates the decay of intact PYP(M)
      and T6(M) at low concentrations (<500 mM) but accelerates decay at high
      concentrations (>1000 mM). For T15(M) and T23(M), NaCl accelerates their decay at
      >100 mM but never decelerates their decay, suggesting that the electrostatic
      interaction, which plays an important role for the recovery of PYP from PYP(M),
      is lost by removing positions 7-15. The electrostatic interaction between this
      region and the beta-scaffold is likely to promote the conformational change of
      PYP(M) for recovery of PYP.

PMID- 14636056
TI  - Photostimulation of a sensory rhodopsin II/HtrII/Tsr fusion chimera activates
      CheA-autophosphorylation and CheY-phosphotransfer in vitro.
AB  - A chimeric fusion protein consisting of Natronomonas pharaonis sensory rhodopsin
      II (SRII), fused by a flexible linker to the two transmembrane helices of its
      cognate transducer protein, HtrII, followed by the HtrII membrane-proximal
      cytoplasmic fragment joined to the cytoplasmic domains of the Escherichia coli
      chemotaxis receptor Tsr, was expressed in E. coli. Purified fusion chimera
      protein reconstituted in liposomes binds to E. coli CheA kinase in the presence
      of the coupling protein CheW, and activates CheA autophosphorylation activity.
      CheA kinase activity is stimulated by photoexcitation of the SRII domain of the
      fusion protein, as shown by the wavelength-dependence of photostimulated
      phosphotransfer to the E. coli flagellar motor response regulator CheY in the
      purified in vitro liposomal system. Further confirming the fidelity of the in
      vitro system, increased and decreased levels of CheA activation in vitro result
      from overmethylated and undermethylated fusion protein purified from
      methylesterase and methyltransferase-deficient E. coli, respectively.
      Photoexcitation of the undermethylated fusion protein resulted in a 3-fold
      increase in phosphotransfer over that of the dark state. The results directly
      demonstrate the coupling of SRII photoactivated states to histidine kinase
      activity, previously predicted on the basis of sequence homologies of the
      haloarchaeal phototaxis system components to those of E. coli chemotaxis. The
      fusion chimera provides the first tool for in vitro measurement of photosignaling
      activity of SRII-HtrII molecular complexes.

PMID- 14636058
TI  - The interaction of the human GGA1 GAT domain with rabaptin-5 is mediated by
      residues on its three-helix bundle.
AB  - GGA proteins regulate clathrin-coated vesicle trafficking by interacting with
      multiple proteins during vesicle assembly. As part of this process, the GAT
      domain of GGA is known to interact with both ARF and Rabaptin-5. Particularly,
      the GAT domains of GGA1 and -2, but not of GGA3, specifically bind with a coiled
      coil region of Rabaptin-5. Rabaptin-5 interacts with Rab5 and is an essential
      component of the fusion machinery for targeting endocytic vesicles to early
      endosomes. The recently determined crystal structure of the GGA1 GAT domain has
      provided insights into its interactions with partner proteins. Here, we describe
      mutagenesis studies on the GAT-Rabaptin-5 interaction. The results demonstrate
      that a hydrophobic surface patch on the C-terminal three-helix bundle motif of
      the GAT domain is directly involved in Rabaptin-5 binding. A GGA3-like mutation,
      N284S, in this Rabaptin-5 binding patch of GGA1 led to a reduced level of
      Rabaptin-5 binding. Furthermore, a reversed mutation, S293N, in GGA3 partially
      establishes Rabaptin-5 binding ability in its GAT domain. These results provide a
      structural explanation for the binding affinity difference among GGA proteins.
      The current results also suggest that the binding of GAT to Rabaptin-5 is
      independent of its interaction with ARF.

PMID- 14636059
TI  - Functional diversity of endothelin pathways in human lung fibroblasts may be
      based on structural diversity of the endothelin receptors.
AB  - Posttranslational modifications of the endothelin receptors A and B from human
      lung fibroblasts were investigated before and after stimulation of the cells with
      (dA)(30)-5'-S-EMC-endothelin-1. The patterns of phosphorylation and
      palmitoylation of both receptors were much more complicated than expected. In
      both the stimulated and the unstimulated states, multiple isoforms differing in
      the number and location of posttranslational modifications were present. MS
      analyses suggested rapid changes in these isoforms following stimulation.
      Overall, the ETA receptor was modified at 20 sites (15 phosphorylation, five
      palmitoylation sites) and ETB at 17 sites (13 phosphorylation, four
      palmitoylation sites). Part of the structural diversity involved
      hypermodification of short sequence regions, and it is suggested that this could
      represent a mechanism for incremental modulation of receptor activity. It is
      postulated that the observed structural diversity over disparate parts of the
      receptor sequences forms the basis for parallel stimulation of different
      signaling pathways at spatially and functionally distinct ET receptors differing
      in posttranslational modifications.

PMID- 14636060
TI  - Rapid changes in the phosphoproteome show diverse cellular responses following
      stimulation of human lung fibroblasts with endothelin-1.
AB  - The rapid phosphorylation and dephosphorylation of a variety of proteins
      downstream of the endothelin receptors A and B was investigated following
      stimulation of human lung fibroblasts with endothelin-1. Changes in the
      phosphorylation of proteins involved in the cell cycle, cytoskeleton, membrane
      channels, transcription, angiogenesis, and metabolism were observed. From
      observed changes in protein phosphatase 2A, CDC25 A, and caspase-2 precursor, a
      model for the promotion of cell cycle progression by ET-1 stimulation is
      proposed. This may offer insights into the mechanisms by which ET-1 exerts its
      mitogenic effects. The identities of the other proteins phosphorylated within 2
      min of stimulation indicate that endothelin-1 also rapidly engages a diverse
      variety of other cellular responses.

PMID- 14636062
TI  - Negative charge at amino acid 149 is the molecular determinant for substrate
      specificity of lecithin: cholesterol acyltransferase for phosphatidylcholine
      containing 20-carbon sn-2 fatty acyl chains.
AB  - We previously described a point mutation in human LCAT (E to A at residue 149;
      hE149A) that demonstrated greater activity with phosphatidylcholine (PC)
      substrate containing 20:4 in the sn-2 position compared with the wild-type enzyme
      [hLCAT; Wang et al. (1997) J. Biol. Chem. 272, 280-286], resulting in a human
      enzyme with the substrate specificity similar to that of rat LCAT. The purpose of
      the present study was to explore the molecular basis for the role of amino acid
      149 in determining fatty acyl substrate specificity. In the first experiment, the
      reverse mutation in rat LCAT (rA149E) converted substrate specificity of rat LCAT
      toward that of the human enzyme, demonstrating that the mutation was context
      independent and reversible. In the second experiment, we found that hE149A
      compared with hLCAT demonstrated higher activity with PC species containing 20
      carbon, but not 18-carbon, sn-2 fatty acyl chains. The increased activity of
      hE149A was due to an increase in apparent V(max) but not to apparent K(m) or LCAT
      binding to the PC surface. Substitution of different amino acids in the 149
      position of hLCAT showed that activation of the enzyme with sn-2 20:4 containing
      PC substrate was only observed when the negative charge at residue 149 was
      removed. We conclude that the negative charge at amino acid 149 of LCAT is a
      critical determinant for the specificity of the enzyme for PC containing 18- vs
      20-carbon sn-2 fatty acyl chains.

PMID- 14636061
TI  - Pancreatic islets and insulinoma cells express a novel isoform of group VIA
      phospholipase A2 (iPLA2 beta) that participates in glucose-stimulated insulin
      secretion and is not produced by alternate splicing of the iPLA2 beta transcript.
AB  - Many cells express a group VIA 84 kDa phospholipase A(2) (iPLA(2)beta) that is
      sensitive to inhibition by a bromoenol lactone (BEL) suicide substrate.
      Inhibition of iPLA(2)beta in pancreatic islets and insulinoma cells suppresses,
      and overexpression of iPLA(2)beta in INS-1 insulinoma cells amplifies, glucose
      stimulated insulin secretion, suggesting that iPLA(2)beta participates in
      secretion. Western blotting analyses reveal that glucose-responsive 832/13 INS-1
      cells express essentially no 84 kDa iPLA(2)beta-immunoreactive protein but
      predominantly express a previously unrecognized immunoreactive iPLA(2)beta
      protein in the 70 kDa region that is not generated by a mechanism of alternate
      splicing of the iPLA(2)beta transcript. To determine if the 70 kDa-immunoreactive
      protein is a short isoform of iPLA(2)beta, protein from the 70 kDa region was
      digested with trypsin and analyzed by mass spectrometry. Such analyses reveal
      several peptides with masses and amino acid sequences that exactly match
      iPLA(2)beta tryptic peptides. Peptide sequences identified in the 70 kDa tryptic
      digest include iPLA(2)beta residues 7-53, suggesting that the N-terminus is
      preserved. We also report here that the 832/13 INS-1 cells express iPLA(2)beta
      catalytic activity and that BEL inhibits secretagogue-stimulated insulin
      secretion from these cells but not the incorporation of arachidonic acid into
      membrane PC pools of these cells. These observations suggest that the catalytic
      iPLA(2)beta activity expressed in 832/13 INS-1 cells is attributable to a short
      isoform of iPLA(2)beta and that this isoform participates in insulin secretory
      but not in membrane phospholipid remodeling pathways. Further, the finding that
      pancreatic islets also express predominantly a 70 kDa iPLA(2)beta-immunoreactive
      protein suggests that a signal transduction role of iPLA(2)beta in the native
      beta-cell might be attributable to a 70 kDa isoform of iPLA(2)beta.

PMID- 14636063
TI  - Studies with chimeras of the gonadotropin receptors reveal the importance of
      third intracellular loop threonines on the formation of the receptor/nonvisual
      arrestin complex.
AB  - Using chimeras and more discrete exchange mutations of the rat (r) and human (h)
      gonadotropin receptors, we had previously identified multiple noncontiguous
      residues of the lutropin (LHR) and follitropin (FSHR) receptors that dictate
      their rates of internalization. Since the internalization of the LHR and the FSHR
      is driven by their abilities to associate with the nonvisual arrestins, we
      hypothesized that one or more of the residues previously identified by the
      internalization assays are involved in the formation of the receptor/nonvisual
      arrestin complex. In the studies reported herein, we tested this hypothesis by
      measuring the association of arrestin-3 with a large number of rLHR/hLHR and
      rFSHR/hFSHR exchange mutants that affect internalization. The results presented
      show that the same residues that dictate the rate of internalization of these two
      receptor pairs affect their ability to associate with arrestin-3. Although these
      residues are located in distinct topological domains, our analyses show that
      threonine residues in the third intracellular loop of both receptor pairs are
      particularly important for the formation of the receptor/arrestin-3 complexes and
      internalization. We conclude that the different rates of internalization of the
      gonadotropin receptors are dictated by their different abilities to associate
      with the nonvisual arrestins and that this association is, in turn, largely
      dictated by the presence of threonine residues in their third intracellular
      loops.

PMID- 14636064
TI  - An endogenous electrophile that modulates the regulatory mechanism of protein
      turnover: inhibitory effects of 15-deoxy-Delta 12,14-prostaglandin J2 on
      proteasome.
AB  - Prostaglandin D(2) (PGD(2)), a major cyclooxygenase product in a variety of
      tissues and cells, readily undergoes dehydration to yield electrophilic PGs, such
      as 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We have previously shown that 15d
      PGJ(2) potently induces apoptosis of SH-SY5Y human neuroblastoma cells via
      accumulation of the tumor suppressor gene product p53. In the study presented
      here, we investigated the molecular mechanisms involved in the 15d-PGJ(2)-induced
      accumulation of p53. It was observed that 15d-PGJ(2) potently induced p53 protein
      expression but scarcely induced p53 gene expression. In addition, exposure of the
      cells to 15d-PGJ(2) resulted in an accumulation of ubiquitinated proteins and in
      a significant inhibition of proteasome activities, suggesting that 15d-PGJ(2)
      acted on the ubiquitin-proteasome pathway, a regulatory mechanism of p53
      turnover. The effects of 15d-PGJ(2) on the protein turnover were attributed to
      its electrophilic feature, based on the observations that (i) the reduction of
      the double bond in the cyclopentenone ring of 15d-PGJ(2) virtually abolished the
      effects on protein turnover, (ii) overexpression of an endogenous redox
      regulator, thioredoxin 1, significantly retarded the inhibition of proteasome
      activities and accumulations of p53 and ubiquitinated proteins induced by 15d
      PGJ(2), and (iii) treatment of SH-SY5Y cells with biotinylated 15d-PGJ(2) indeed
      resulted in the formation of a 15d-PGJ(2)-proteasome conjugate. These data
      suggest that the modulation of proteasome activity may be involved in the
      mechanism responsible for the accumulation of p53 and subsequent induction of
      apoptotic cell death induced by 15d-PGJ(2).

PMID- 14636065
TI  - TetL tetracycline efflux protein from Bacillus subtilis is a dimer in the
      membrane and in detergent solution.
AB  - The TetL antiporter from the Bacillus subtilis inner membrane is a tetracycline
      divalent cation efflux protein that is energized by the electrochemical proton
      gradient across the membrane. In this study, we expressed tetL in Escherichia
      coli and investigated the oligomeric state of TetL in the membrane and in
      detergent solution. Evidence for an oligomeric state of TetL emerged from SDS
      PAGE and Western blot analysis of membrane samples as well as purified protein
      samples from cells that expressed two differently tagged TetL species.
      Furthermore, no formation or restoration of TetL oligomers occurred upon
      detergent solubilization of the membrane. Rather, oligomeric forms established in
      vivo persisted after solubilization. Mass spectrometry of the purified protein
      showed the absence of proteolysis and posttranslational modifications. Analytical
      size-exclusion chromatography of the purified protein revealed a dimeric TetL in
      dodecyl-maltoside solution. In addition, TetL dimers were found in a number of
      other detergents and over a wide pH range. It is therefore likely that the
      oligomeric form of the protein in the membrane is also a dimer.

PMID- 14636066
TI  - Gamma-secretase activity is present in rafts but is not cholesterol-dependent.
AB  - Cholesterol has been claimed to be involved in the generation and/or accumulation
      of amyloid beta protein (Abeta). However, the underlying molecular mechanisms
      have not been fully elucidated yet. Here, we have investigated the effect of
      membrane cholesterol content on gamma-secretase activity using Chinese hamster
      ovary cells stably expressing beta-amyloid precursor protein (APP) and either
      wild-type or N141I mutant-type presenilin 2. Cholesterol was acutely depleted
      from the isolated membrane by methyl-beta-cyclodextrin, and Abeta production was
      assessed in a cell-free assay system. Reduced cholesterol did not significantly
      alter the amounts of Abeta produced by either total cell membranes or cholesterol
      rich low-density membrane domains. Even its extremely low levels in the latter
      domains did not affect Abeta production. This indicates that the membrane
      cholesterol content does not directly modulate the activity of gamma-secretase.
      To ascertain that gamma-secretase resides in cholesterol-rich membrane domains,
      low-density membrane domains were further fractionated with BCtheta (biotinylated
      theta-toxin nicked with subtilisin Carlsberg protease), which has recently been
      shown to bind selectively to rafts of intact cells. The membrane domains purified
      with BCtheta did indeed produce Abeta. These observations indicate that the gamma
      cleavage required for generating Abeta occurs in rafts, but its activity is
      virtually cholesterol-independent.

PMID- 14636067
TI  - Combined triplex/duplex invasion of double-stranded DNA by "tail-clamp" peptide
      nucleic acid.
AB  - "Tail-clamp" PNAs composed of a short (hexamer) homopyrimidine triplex forming
      domain and a (decamer) mixed sequence duplex forming extension have been
      designed. Tail-clamp PNAs display significantly increased binding to single
      stranded DNA compared with PNAs lacking a duplex-forming extension as determined
      by T(m) measurements. Binding to double-stranded (ds) DNA occurred by combined
      triplex and duplex invasion as analyzed by permanganate probing. Furthermore,
      C(50) measurements revealed that tail-clamp PNAs consistently bound the dsDNA
      target more efficiently, and kinetics experiments revealed that this was due to a
      dramatically reduced dissociation rate of such complexes. Increasing the PNA net
      charge also increased binding efficiency, but unexpectedly, this increase was
      much more pronounced for tailless-clamp PNAs than for tail-clamp PNAs. Finally,
      shortening the tail-clamp PNA triplex invasion moiety to five residues was
      feasible, but four bases were not sufficient to yield detectable dsDNA binding.
      The results validate the tail-clamp PNA concept and expand the applications of
      the P-loop technology.

PMID- 14636068
TI  - Extending recognition by peptide nucleic acids (PNAs): binding to duplex DNA and
      inhibition of transcription by tail-clamp PNA-peptide conjugates.
AB  - Peptide nucleic acids (PNAs) are a powerful tool for recognition of double
      stranded DNA. Strand invasion is most efficient when pyrimidine PNAs are linked
      to form a bisPNA in which one strand binds by Watson-Crick base pairing while the
      other binds by Hoogsteen base pairing to the newly formed PNA-DNA duplex. Within
      many genes, however, polypyrimidine target sequences may not be located in
      optimal positions relative to transcription factor binding sites, and this
      deficiency may complicate attempts to identify potent antigene PNAs. To increase
      the versatility of strand invasion by PNAs, we have synthesized bisPNAs and
      bisPNA-peptide conjugates containing a mixed base extension of the Watson-Crick
      polypyrimidine strand. We find that these tail-clamp PNAs (TC-PNAs) bind duplex
      DNA and inhibit transcription. DNA recognition occurs with single-stranded or TC
      bisPNAs and requires attachment of positively charged amino acids. Association
      rate constants, k(a), for binding to DNA by TC-PNAs are as high as 35000 M(-1) s(
      1) and are usually only a fewfold lower than for analogous PNAs that lack mixed
      base extensions. The ability to bind duplex DNA is not always necessary for
      inhibition of transcription, possibly because PNAs can bind to accessible DNA
      within the transcription bubble created by RNA polymerase. These results,
      together with similar findings independently obtained by Nielsen and colleagues
      [Bentin, T., Larsen, H. J., and Nielsen, P. E. (2003) Biochemistry 42, 13987
      13995], expand the range of sequences within duplex DNA that are accessible to
      PNAs and suggest that TC-PNA-peptide conjugates are good candidates for further
      testing as antigene agents.

PMID- 14636069
TI  - Perturbation from a distance: mutations that alter LacI function through long
      range effects.
AB  - Allosteric modification of ligand binding is central to LacI transcription
      control. Recently, the conformational change between LacI operator- and inducer
      bound states was simulated with targeted molecular dynamics (TMD) [Flynn, T. C.,
      Swint-Kruse, L., Kong, Y., Booth, C., Matthews, K. S., and Ma, J. (2003) Protein
      Sci., 12, 2523-2541]. Atomic-level analyses of TMD results indicate the
      structural importance of the core pivot region that connects the N- and C
      subdomains flanking the inducer-binding site. Further, a number of LacI mutations
      in the core pivot have been identified recently by their altered behaviors in
      phenotypic screens. Biochemical characterization of three of these variants
      L148F, S151P, and P320A-provides an opportunity to directly explore the role of
      the core pivot in repressor function. For L148F, inducer IPTG binding affinity is
      strengthened, whereas O(1) operator DNA binding is diminished approximately 30
      fold. In contrast, O(1) binding is increased for S151P, whereas IPTG binding is
      decreased. UV-difference spectroscopy and urea denaturation indicate long-range
      effects in both variants. Interestingly, P320A binds to DNA approximately 4-fold
      more tightly than wild-type, yet inducer binding is unaffected. To examine
      linkage between the core pivot and DNA binding domains, the L148F substitution
      was combined with Q60G, a previously known mutant with enhanced operator
      affinity. The double mutant exhibits the properties of both parent proteins,
      resulting in near wild-type DNA binding affinity and enhanced inducer
      sensitivity. These features may render Q60G/L148F more cost-effective in
      technological applications than wild-type repressor. As a group, the behaviors of
      the core pivot mutants are consistent with the allosteric structural role
      predicted for this region by TMD and reflect the significant long-range impact
      that single substitutions can elicit on protein function.

PMID- 14636070
TI  - Downscaling Fourier transform infrared spectroscopy to the micrometer and
      nanogram scale: secondary structure of serotonin and acetylcholine receptors.
AB  - High signal-to-noise Fourier transform infrared (FTIR) spectra of the 5
      hydroxytryptamine (serotonin) receptor (5-HT(3)R) and the nicotinic acetylcholine
      receptor (nAChR) were obtained by microscope FTIR spectroscopy using micrometer
      sized, fully hydrated protein films. Because this novel procedure requires only
      nanogram quantities of membrane proteins, which is 4-5 orders of magnitude less
      than the amount of protein typically used for conventional FTIR spectroscopy, it
      opens the possibility to access the structure and dynamics of many important
      mammalian receptor proteins. The secondary structure of detergent-solubilized 5
      HT(3)R determined by curve fitting of the amide I band yielded 36% alpha-helix,
      33% beta-strand, 15% beta-turn, and 16% nonregular structures, which remained
      unchanged upon reconstitution in lipid membranes. From hydrogen-deuterium
      exchange, the secondary structure of the water-accessible part of 5-HT(3)R was
      determined as 14% alpha-helix, 16% beta-strand, 26% beta-turn, and 14% nonregular
      structures. Interestingly, we found that both the overall and the water
      accessible nAChR secondary structures were nearly identical to those of 5-HT(3)R,
      in agreement with predicted structures of this class of receptors. This is the
      first time that structural investigations were obtained for two closely related
      ligand-gated ion channels under strictly identical experimental conditions.

PMID- 14636072
TI  - Metmyoglobin and methemoglobin catalyze the isomerization of peroxynitrite to
      nitrate.
AB  - Hemoproteins, in particular, myoglobin and hemoglobin, are among the major
      targets of peroxynitrite in vivo. The oxygenated forms of these proteins are
      oxidized by peroxynitrite to their corresponding iron(iii) forms (metMb and
      metHb). This reaction has previously been shown to proceed via the corresponding
      oxoiron(iv) forms of the proteins. In this paper, we have conclusively shown that
      metMb and metHb catalyze the isomerization of peroxynitrite to nitrate. The
      catalytic rate constants were determined by stopped-flow spectroscopy in the
      presence and absence of 1.2 mM CO(2) at 20 and 37 degrees C. The values obtained
      for metMb and metHb, with no added CO(2) at pH 7.0 and 20 degrees C, are (7.7 +/-
      0.1) x 10(4) and (3.9 +/- 0.2) x 10(4) M(-1) s(-1), respectively. The pH
      dependence of the catalytic rate constants indicates that HOONO is the species
      that reacts with the iron(iii) center of the proteins. In the presence of 1.2 mM
      CO(2), metMb and metHb also accelerate the decay of peroxynitrite in a
      concentration-dependent way. However, experiments carried out at pH 8.3 in the
      presence of 10 mM CO(2) suggest that ONOOCO(2)(-), the species generated from the
      reaction of ONOO(-) with CO(2), does not react with the iron(iii) center of Mb
      and Hb. Finally, we showed that different forms of Mb and Hb protect free
      tyrosine from peroxynitrite-mediated nitration. The order of efficiency is
      metMbCN < apoMb < metHb < metMb < ferrylMb < oxyHb < deoxyHb < oxyMb. Taken
      together, our data show that myoglobin is always a better scavenger than
      hemoglobin. Moreover, the globin offers very little protection, as the heme-free
      (apoMb) and heme-blocked (metMbCN) forms only partly prevent nitration of free
      tyrosine.

PMID- 14636071
TI  - Ranacyclins, a new family of short cyclic antimicrobial peptides: biological
      function, mode of action, and parameters involved in target specificity.
AB  - We report on two new cyclic 17-residue peptides that we named ranacyclins E and
      T, the first isolated from Rana esculenta frog skin secretions and the second
      discovered by screening a cDNA library from Rana temporaria. Ranacyclins have a
      loop region that is homologous with that of an 18-mer peptide, pLR, isolated from
      the skin of the Northern Leopard frog, Rana pipiens, with no reported
      antimicrobial activity. Here we show that ranacyclins and pLR have antimicrobial
      and antifungal activity. However, despite the high structural similarity, they
      differ in their spectrum of activity. The data reveal that ranacyclins and pLR
      have several properties that differentiate them from most known antimicrobial
      peptides. These include the following: (i) they adopt a significant portion of
      random coil structure in the membrane as revealed by ATR-FTIR and CD spectroscopy
      (50% for ranacyclin T and 70% for both ranacyclin E and pLR); (ii) they bind
      similarly to both zwitterionic and negatively charged membranes as revealed by
      using tryptophan fluorescence and surface plasmon resonance (SPR; BIAcore
      biosensor); (iii) they insert into the hydrophobic core of the membrane and
      presumably form transmembrane pores without damage to the bacterial wall, as
      revealed by SPR, ATR-FTIR, and transmission electron microscopy (TEM); and (iv)
      despite being highly and equally active in permeating bacterial spheroplasts and
      negatively charged membranes, they differ significantly in their potencies
      against target cells. Furthermore, a significant fraction of a given secondary
      structure is not prerequisite for membrane permeation and antimicrobial activity.
      However, increasing the fraction of a secondary structure and reducing peptide
      assembly in the membrane make it easier for the peptide to diffuse through the
      cell wall, which is different for each microorganism, into the cytoplasmic
      membrane.

PMID- 14636073
TI  - Core formation in Escherichia coli bacterioferritin requires a functional
      ferroxidase center.
AB  - Bacterioferritin from Escherichia coli is able to accumulate large quantities of
      iron in the form of an inorganic iron(III) mineral core. Core formation in the
      wild-type protein and a number of ferroxidase center variants was studied to
      determine key features of the core formation process and, in particular, the role
      played by the ferroxidase center. Core formation rates were found to be iron(II)
      dependent and also depended on the amount of iron already present in the core,
      indicating the importance of the core surface in the mineralization reaction.
      Core formation was also found to be pH-dependent in terms of both rate and iron
      loading characteristics, occurring with maximum efficiency at pH 6.5. Even at
      this optimum pH, however, the effective iron capacity was approximately 2700 per
      molecule, i.e., well below the theoretical limit of approximately 4500,
      suggesting that competing oxidation/precipitation processes have a major
      influence on the amount of iron accumulated. Disruption of the ferroxidase
      center, by site-directed mutagenesis or by chemical inhibition with zinc(II), had
      a profound effect on core formation. Effective iron capacities were found to be
      linked to iron(II) oxidation rates, and in zinc(II)-inhibited wild-type and E18A
      bacterioferritins core formation was severely restricted. Zinc(II) was also able,
      even at low stoichiometries (12-60 ions/protein), to significantly inhibit
      further core formation in protein already containing a substantial core,
      indicating the importance of the ferroxidase center throughout the core formation
      process. A mechanism is proposed that incorporates essential roles for the core
      surface and the ferroxidase center. A central feature of this mechanism is that
      dioxygen cannot readily gain access to the core, perhaps because the channels
      through the bacterioferritin coat are hydrophilic and dioxygen is nonpolar.

PMID- 14636074
TI  - Steady-state kinetics and tryptophan fluorescence properties of halohydrin
      dehalogenase from Agrobacterium radiobacter. Roles of W139 and W249 in the active
      site and halide-induced conformational change.
AB  - Halohydrin dehalogenase (HheC) from Agrobacterium radiobacter AD1 is a
      homotetrameric protein containing four tryptophan residues per subunit. The
      fluorescence properties of the enzyme are strongly influenced by halide binding.
      To examine the role of the tryptophans (W139, W192, W238, and W249) in halide
      binding and catalysis, they were individually mutated to a phenylalanine. All
      mutations, except for W238F, influenced the enzymatic properties. Mutating W192
      to phenylalanine inactivated the enzyme and led to dissociation into dimers and
      monomers. In the structure of HheC, residue W139 and residue W249 from the
      opposite subunit are close to the active site of the enzyme. Substitution of W139
      mainly affected K(m) values with all tested substrates and reduced the
      enantiopreference for p-nitro-2-bromo-1-phenylethanol. Replacing W249 increased
      both k(cat) and K(m) values with all tested substrates except for the (S)
      enantiomer of p-nitro-2-bromo-1-phenylethanol, for which k(cat) was 3-fold
      decreased, resulting in a 6-fold increase of the enantioselectivity. Fluorescence
      measurements revealed that in the ligand-free state the intrinsic protein
      fluorescence of mutant W139F is higher than that of the wild-type enzyme, while
      the fluorescence intensity of mutants W238F and W249F was lower. The fluorescence
      intensities of the W238F and W249F enzymes were increased when they were unfolded
      or when bromide was added, whereas the fluorescence of mutant W139F was not
      increased by unfolding or addition of bromide. These results demonstrate that the
      fluorescence of residues W238 and W249 is partially quenched in the folded ligand
      free state, and that W139 is completely quenched and acts as an energy acceptor
      for the other tryptophan residues as well. Changes of the maximum fluorescence
      emission wavelength of the HheC variants and the results of acrylamide quenching
      experiments confirmed that bromide binding induces a local conformational change
      around the active site, resulting in residue W139 and the quencher group being
      separated.

PMID- 14636075
TI  - New insight into the peroxidase-hydroxamic acid interaction revealed by the
      combination of spectroscopic and crystallographic studies.
AB  - Aromatic hydroxamic acids, such as salicylhydroxamic (SHA) and benzohydroxamic
      (BHA) acids, are commonly used as probes for studying the active sites of
      peroxidases. In this paper, we have extended the study of the complexes of
      Arthromyces ramosus peroxidase (ARP/CIP) with BHA and SHA by analyzing their
      Raman spectra in solution and in single crystals. The experiments were carried
      out under various conditions to identify the best experimental conditions, and
      hence, avoid artifacts deriving from the preparation of the samples or collection
      of the spectra. The analysis of the data takes also into account the
      characteristic of the electronic absorption spectra in solution and the crystal
      structures of the complexes. The results showed small differences between the
      solution and the crystal phases even though the coordination state can be
      dramatically affected by the physical or chemical conditions. The greater
      sensitivity of the spectroscopic technique enabled us to establish the existence
      of multiple species upon complexation of the protein with the hydroxamic acids
      that could not be detected by ordinary X-ray crystallography. Furthermore, SHA
      titration experiments and singular value decomposition analysis of the absorption
      spectra indicated the presence of two binding sites in the protein, one with a
      high affinity (K(d) = 1.7 mM), which should correspond to the SHA bound protein
      as determined by X-ray, and the other with a very low affinity (K(d) > 80 mM)
      probably located in a non-heme site. This suggests that the heterogeneous
      titration line shape involves ligand binding to a non-heme site in competition
      with the canonical heme site. In contrast, the titration profile obtained with
      the BHA ligand is monophasic, in agreement with all the peroxidases so far
      studied.

PMID- 14636076
TI  - Mechanism of phosphatase activity in the chemotaxis response regulator CheY.
AB  - Response regulator proteins are phosphorylated on a conserved aspartate to
      activate responses to environmental signals. An intrinsic autophosphatase
      activity limits the duration of the phosphorylated state. We have previously
      hypothesized that dephosphorylation might proceed through an intramolecular
      attack, leading to succinimide formation, and such an intramolecular
      dephosphorylation event is seen for CheY and OmpR during mass spectrometric
      analysis [Napper, S., Wolanin, P. M., Webre, D. J., Kindrachuk, J., Waygood, B.,
      and Stock, J. B. (2003) FEBS Lett 538, 77-80]. Succinimide formation is usually
      associated with the spontaneous deamidation of Asn residues. We show here that an
      Asp57 to Asn mutant of the CheY chemotaxis response regulator undergoes an
      unusually rapid deamidation back to the wild-type Asp57, supporting the
      hypothesis that the active site of CheY is poised for succinimide formation. In
      contrast, we also show that the major route of phosphoaspartate hydrolysis in
      CheY occurs through water attack on the phosphorus both during autophosphatase
      activity and during CheZ-mediated dephosphorylation. Thus, CheY dephosphorylation
      does not usually proceed via a succinimide or any other intramolecular attack.

PMID- 14636077
TI  - Metabolic complications associated with HIV protease inhibitor therapy.
AB  - HIV protease inhibitors were introduced into clinical practice over 7 years ago
      as an important component of combination antiretroviral drug regimens which in
      many ways revolutionised the treatment of HIV infection. The significant
      improvements in prognosis that have resulted from the use of these regimens,
      combined with the need for lifelong treatment, have increasingly focused
      attention on the adverse effects of antiretroviral drugs and on the metabolic
      complications of HIV protease inhibitors in particular. In this review, the
      cluster of metabolic abnormalities characterised by triglyceride-rich
      dyslipidaemia and insulin resistance associated with HIV protease inhibitor
      therapy are considered, along with implications for cardiovascular risk in
      patients affected by these complications. Toxicity profiles of individual drugs
      within the HIV protease inhibitor class are examined, as there is an increased
      recognition of significant intra-class differences both in terms of absolute risk
      of metabolic complications as well as the particular metabolic phenotype
      associated with these drugs. Guidelines for clinical assessment and treatment are
      emphasised, along with pathophysiological mechanisms that may provide a rational
      basis for the treatment of metabolic complications. Finally, these drug-specific
      effects are considered within the context of HIV-specific effects on lipid
      metabolism as well as lifestyle factors that have contributed to a rapidly
      increasing incidence of similar metabolic syndromes in the general population.
      These data highlight the importance of individualising patient management in
      terms of choice of antiretroviral regimen, assessment of metabolic outcomes and
      use of therapeutic interventions, based on the assessment of baseline (pre
      treatment) metabolic status as well as the presence of potentially modifiable
      cardiovascular risk factors.

PMID- 14636078
TI  - Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease.
AB  - Phosphodiesterases (PDE) belong to an important family of proteins that regulate
      the intracellular levels of cyclic nucleotide second messengers. Targeting PDE
      with selective inhibitors may offer novel therapeutic strategies in the treatment
      of various conditions, and in the context of respiratory disease these include
      asthma and chronic obstructive pulmonary disease (COPD). The rationale for such
      an approach stems, in part, from the clinical efficacy of theophylline, an orally
      active drug that is purportedly a nonselective PDE inhibitor. In addition,
      intracellular cyclic adenosine monophosphate (cAMP) levels regulate the function
      of many of the cells thought to contribute to the pathogenesis of respiratory
      diseases such as asthma and COPD, and these cells also selectively express PDE4.
      This has offered pharmaceutical companies the opportunity to selectively
      targeting these enzymes for the treatment of these diseases. Finally, the success
      of targeting PDE5 in the treatment of erectile dysfunction provides clinical
      proof of concept for the targeting of PDE in disease. Whether a 'Viagra' of the
      airways can be found for the treatment of asthma and COPD remains to be seen, but
      positive results from recent clinical studies examining the efficacy of selective
      PDE4 inhibitors such as cilomilast and roflumilast offer some optimism. However,
      one of the major issues to be resolved is the tolerability profile associated
      with this drug class that is a consequence of PDE4 inhibition. While cilomilast
      and roflumilast have low emetic potential they are not free from emesis and
      various strategies are being investigated in the hope of developing a PDE4
      inhibitor without this adverse effect.

PMID- 14636080
TI  - Azelnidipine.
AB  - Azelnidipine is a new dihydropyridine calcium channel antagonist with selectivity
      for L-type calcium channels that has recently been approved in Japan for the
      treatment of patients with hypertension. Results from clinical trials showed
      that, in 95 patients with mild-to-moderate hypertension, long-term treatment with
      azelnidipine effectively controls blood pressure (BP). The mean reduction from
      baseline in sitting systolic/diastolic BP after 1 year of treatment was 27.8/16.6
      mm Hg. Among 172 patients with uncontrolled hypertension receiving non-calcium
      channel antagonist antihypertensive agents, the addition of azelnidipine therapy
      significantly reduced mean BP in a noncomparative, 1-year study (a reduction from
      165.7/95.4 mm Hg at baseline to 138.2/79.9 mm Hg at study end). The
      antihypertensive efficacy of azelnidipine in patients with mild-to-moderate
      hypertension was shown to be similar to that of amlodipine or nitrendipine in
      randomised, double-blind studies. Azelnidipine and amlodipine controlled 24-hour
      BP to a similar extent. Azelnidipine is generally well tolerated; vasodilator
      adverse events such as as headache and hot facial flushes account for most of the
      adverse events. Its use is not associated with reflex tachycardia.

PMID- 14636079
TI  - CNS involvement in overactive bladder: pathophysiology and opportunities for
      pharmacological intervention.
AB  - The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves
      both peripheral and CNS factors. Several CNS disorders are associated with OAB,
      e.g. stroke, spinal cord injury, Parkinson's disease and multiple sclerosis, and
      in each disorder the pathophysiology of OAB can be multifactorial. Irrespective
      of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of
      pharmacological treatment. However, adverse effects and limited efficacy makes
      alternative therapeutic principles desirable. Most alternative drugs used for the
      treatment of OAB have a peripheral site of action, mainly affecting efferent or
      afferent neurotransmission or the detrusor muscle itself. New targets for
      pharmacological intervention may be found in the CNS. Several CNS
      transmitters/transmitter systems are known to be involved in micturition control,
      but few drugs with a defined CNS site of action (e.g. baclofen, imipramine and
      duloxetine) have been used for the treatment of voiding disorders. GABA,
      glutamate, opioid, serotonin, noradrenaline (norepinephrine), and dopamine
      receptors and mechanisms are known to influence micturition, and drugs
      influencing these systems could potentially be developed for the treatment of
      OAB. Preclinical studies in different animal models have shown that modulation of
      normal micturition and detrusor overactivity by drugs acting within the spinal
      cord or supraspinally is possible. Promising results have been obtained in such
      models, e.g. with drugs interfering with GABA mechanisms, serotonin 5-HT1A
      receptors, mu-opioid receptors and alpha-adrenoreceptors. However, considering
      the limited predictability of existing animal models for efficacy in humans,
      positive proof of concept studies in humans are mandatory. Such studies are
      scarce and further investigations are needed.

PMID- 14636084
TI  - Combined hepatitis A and B vaccines: a review of their immunogenicity and
      tolerability.
AB  - Three combined hepatitis A and B vaccine preparations are commercially available
      in various countries: a two-dose paediatric formulation (Ambirix) [administered
      at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric
      (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult
      vaccine provides consistent, marked immunogenicity which is at least similar to
      that of its constituent vaccines used together and with a tolerability profile
      that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also
      shown immunogenicity similar to that of the monovalent vaccines given
      concurrently, and now has an emerging role in adults likely to travel to
      hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1
      month. The adult vaccine appears effective and generally well tolerated when
      given concurrently with monovalent typhoid vaccine (Typherix). Immunogenicity of
      the two-dose paediatric vaccine is high and appears to be similar whether
      administered as a month-0, -6 or month-0, -12 schedule and when compared to that
      of the three-dose paediatric vaccine (months 0, 1, 6), both of which provide a
      similar degree of protection to the adult vaccine. Although both preparations
      also provide high end-of-schedule seroprotection against hepatitis B surface
      antigen, protection between the first and second doses of the two-dose regimen
      appears lower than with the three-dose schedule. Therefore, the three-dose
      paediatric vaccine is a practical option in individuals at risk of immediate
      exposure to HBV, while the two-dose regimen may have an important function in
      immunisation programmes in regions where such risk is low. Combined hepatitis A
      and B vaccines are generally well tolerated. The most frequently reported adverse
      events in clinical trials were injection-site pain and redness, and general
      fatigue and headache; most events were mild and transient. Pharmacoeconomic
      models suggest the combined vaccine is cost effective compared with no vaccine
      (in children/adolescents) or monovalent hepatitis B vaccine (in
      children/adolescents and prison inmates). CONCLUSION: The three commercially
      available combined hepatitis A and B adult and paediatric vaccines are highly
      immunogenic and generally well tolerated; the adult vaccine demonstrates
      immunogenicity at least as marked as that of monovalent hepatitis A and B
      vaccines. While further research is required to confirm potential advantages such
      as improved cost effectiveness, the combined vaccines have established a key role
      in the prevention of hepatitis A and B in defined risk groups, and have an
      expanding role in population-based vaccination programmes with younger age
      groups.

PMID- 14636086
TI  - Vardenafil: a review of its use in erectile dysfunction.
AB  - Vardenafil (Levitra) is a potent and highly selective oral phosphodiesterase type
      5 (PDE5) inhibitor. Vardenafil improved erectile function in men with mild to
      severe erectile dysfunction (ED) of varying aetiology in two randomised, double
      blind, multicentre, fixed-dose studies of 12 or 26 weeks' duration. Men receiving
      vardenafil 10 or 20 mg had significantly greater improvements in International
      Index of Erectile Function (IIEF) questionnaire erectile function domain scores
      than placebo recipients. Moreover, improvements in penetration and maintenance of
      erection (assessed using IIEF or Sexual Encounter Profile [SEP] questions) were
      significantly greater with vardenafil 5-20 mg than with placebo. Improvements in
      IIEF intercourse satisfaction and orgasmic function domain scores were
      significantly greater with vardenafil 10 or 20 mg than with placebo and the
      proportion of patients with a positive response to a Global Assessment Question
      (GAQ) concerning improvement in erections after 12 or 26 weeks' therapy was
      significantly higher with vardenafil 5-20 mg than with placebo. Vardenafil
      improved erectile function in men with ED associated with diabetes mellitus or ED
      following unilateral or bilateral nerve-sparing radical retropubic prostatectomy
      in two randomised, double-blind, multicentre, fixed-dose, 3-month studies. In
      both studies, improvements from baseline in the erectile function domain score of
      the IIEF and in positive responses to SEP questions were significantly greater
      with vardenafil 10 or 20 mg than with placebo. In addition, a significantly
      higher proportion of vardenafil 10 or 20 mg recipients than placebo recipients
      had positive GAQ responses. Vardenafil was generally well tolerated in men with
      ED; treatment-emergent adverse events were of mild to moderate intensity and
      transient in nature. The most commonly reported adverse events (typical of those
      seen with PDE5 inhibitors) in vardenafil 5-20 mg recipients included headache,
      flushing, rhinitis, dyspepsia and sinusitis. There were no reports of abnormal
      colour vision in men with ED taking vardenafil at clinically recommended doses (5
      20 mg). CONCLUSION: Vardenafil is a potent and highly selective oral PDE5
      inhibitor. It is effective and generally well tolerated in men with mild to
      severe ED of varying aetiology, as well as in men with ED associated with
      diabetes mellitus or ED after radical prostatectomy. Vardenafil should be
      considered a first-line treatment option in men with ED who are suitable
      candidates for oral PDE5 inhibitor therapy.

PMID- 14636085
TI  - Levosimendan: a review of its use in the management of acute decompensated heart
      failure.
AB  - Levosimendan (Simdax) is a calcium-sensitising drug that stabilises the troponin
      molecule in cardiac muscle, thus prolonging its effects on contractile proteins,
      with concomitant vasodilating properties. Intravenous levosimendan (12-24
      microg/kg loading dose followed by 0.1-0.2 microg/kg/min for 24 hours, adjusted
      for response and tolerability) is approved for the short-term treatment of acute
      severe decompensated heart failure. Cardiac output increased by about 30% and
      pulmonary capillary wedge pressure and systemic vascular resistance decreased by
      about 17-29% in patients with decompensated heart failure receiving intravenous
      levosimendan. In large, well controlled trials in patients with decompensated
      heart failure, intravenous levosimendan was significantly more effective than
      placebo or dobutamine for overall haemodynamic response rate (primary endpoint).
      Significant benefits were also seen for mortality (versus placebo or dobutamine)
      and for the combined risk of worsening heart failure or death (versus
      dobutamine). Improvements in key symptoms (dyspnoea and fatigue) have not been
      consistently demonstrated. Hospitalisation costs were similar for levosimendan
      and dobutamine; the total incremental (hospitalisation plus drug) cost per life
      year saved (extrapolated to 3 years) for levosimendan relative to dobutamine was
      estimated at Euro 3205 (year of costing 2000). Levosimendan is generally well
      tolerated, with an adverse event profile at recommended dosages similar to that
      in patients receiving placebo. Cardiac rate/rhythm disorders and headache were
      the most common events. At higher dosages, patients receiving levosimendan had
      higher rates of sinus tachycardia than those in placebo recipients. More patients
      receiving dobutamine than those receiving levosimendan experienced angina
      pectoris/chest pain/myocardial ischaemia or rate/rhythm disorders. CONCLUSION:
      Intravenous levosimendan is an effective calcium-sensitising drug with
      vasodilatory and inotropic effects, and superior efficacy/tolerability to those
      of intravenous dobutamine in patients with acute decompensated heart failure. It
      may be associated with reduced mortality compared with both placebo and
      dobutamine. Levosimendan is generally well tolerated and may have less potential
      for cardiac rate/rhythm disorders than dobutamine. While evidence from well
      designed trials confirming the improved mortality over dobutamine and
      investigating haemodynamic efficacy and mortality versus other positive inotropes
      is required, intravenous levosimendan appears to be a useful addition to the
      treatment options for acute decompensated heart failure in patients with low
      cardiac output.

PMID- 14636087
TI  - Effect of warm-up on the standing broad jump in trained and untrained men and
      women.
AB  - The effect of 3 warm-up routines on standing broad jump (SBJ) performance was
      investigated. Thirty-two men and women participated as subjects. Following the
      determination of 1-repetition maximum (1RM) squat, subjects completed warm-up
      routines and broad jumps on 4 occasions in a randomized order. Subjects performed
      SBJ immediately (POST) and 15 min following (POST15) the given warm-up routine.
      The routines were high force, consisting of high % 1RM, low repetition squats;
      high power, consisting of low % 1RM, low repetition speed squats; stretching,
      consisting of static stretches; and no activity, a control condition. Repeated
      measures analysis of covariance (ANCOVA) revealed no differences among broad jump
      performance following any of the warm-up routines (p = 0.157). A strong
      correlation (R = 0.805) was found between 1RM squat and SBJ. These data indicate
      that warm-up of any type has little effect on jump performance and that maximum
      strength is strongly related to jumping ability.

PMID- 14636088
TI  - Effects of plyometric training and recovery on vertical jump performance and
      anaerobic power.
AB  - We examined the effects of 2 plyometric training programs, equalized for training
      volume, followed by a 4-week recovery period of no plyometric training on
      anaerobic power and vertical jump performance. Physically active, college-aged
      men were randomly assigned to either a 4-week (n = 19, weight = 73.4 +/- 7.5 kg)
      or a 7-week (n = 19, weight = 80.1 +/- 12.5 kg) program. Vertical jump height,
      vertical jump power, and anaerobic power via the Margaria staircase test were
      measured pretraining (PRE), immediately posttraining (POST), and 4 weeks
      posttraining (POST-4). Vertical jump height decreased in the 4-week group PRE
      (67.8 +/- 7.9 cm) to POST (65.4 +/- 7.8 cm). Vertical jump height increased from
      PRE to POST-4 in 4-week (67.8 +/- 7.9 to 69.7 +/- 7.6 cm) and 7-week (64.6 +/-
      6.2 to 67.2 +/- 7.6 cm) training programs. Vertical jump power decreased in the 4
      week group from PRE (8,660.0 +/- 546.5 W) to POST (8,541.6 +/- 557.4 W) with no
      change in the 7-week group. Vertical jump power increased PRE to POST-4 in 4-week
      (8,660.0 +/- 546.5 W to 8,793.6 +/- 541.4 W) and 7-week (8,702.8 +/- 527.4 W to
      8,931.5 +/- 537.6 W) training programs. Anaerobic power improved in the 7-week
      group from PRE (1,121.9 +/- 174.7 W) to POST (1,192.2 +/- 189.1 W) but not the 4
      week group. Anaerobic power significantly improved PRE to POST-4 in both groups.
      There were no significant differences between the 2 training groups. Four-week
      and 7-week plyometric programs are equally effective for improving vertical jump
      height, vertical jump power, and anaerobic power when followed by a 4-week
      recovery period. However, a 4-week program may not be as effective as a 7-week
      program if the recovery period is not employed.

PMID- 14636089
TI  - Technical-methodological report: a nomogram for peak leg power output in the
      vertical jump.
AB  - Leg power is an important component in assessing both performance-related and
      health-related fitness. The Lewis equation and nomogram have been used for years
      to estimate leg power. A recent evaluation of the Lewis equation and further
      research led to the development of the Sayers equation. This equation provides an
      estimate of peak leg power, which has greater relevance than average power. Our
      purpose was to provide a simple and effective nomogram for calculating peak leg
      power output. The Sayers equation was transformed to an alignment nomogram and
      evaluated for facility of use and accuracy. The resultant alignment nomogram is
      easy to use and generates values for peak leg power in the vertical jump, which
      are well within the precision of the regression equation (r > 0.9999, CV < 0.2%).
      Interobserver error was less than 0.3% with a correlation of 0.9999. The Keir
      nomogram provides a simple and effective representation of the Sayers equation
      for use in both performance-related and health-related fitness assessments.

PMID- 14636090
TI  - A biomechanical analysis of the acute effects of complex training using lower
      limb exercises.
AB  - The aim of this study was to investigate the current practice of complex training
      using a lower body combination of exercises. It was hypothesized that a bout of
      heavy resistance exercise (HRE), as typically used in complex training, would
      lead to enhanced performance (in the form of counter-movement [CMJ] and drop [DJ]
      jump height) and increased electromyographical (EMG) activity in subsequent
      plyometric exercise, also typical of complex training. Eight strength trained men
      performed 2 conditions: HRE or control (no-HRE) in a counter-balanced order. Both
      conditions involved 4 sets of 6-jump trials (3-CMJ/ 3-DJ). The first set of jumps
      was used as a baseline. For the HRE condition, 5-squats at 85% of 1 repetition
      maximum (1RM) followed shortly after the first set, while the second, third and
      fourth sets followed at 3-, 10-, and 20-minutes post-HRE, respectively. The
      control condition involved the same procedure, but no exercise separated the
      first 2-sets. There were no significant main effects (p > 0.05) for any CMJ
      performance variable or EMG activity regardless of muscle or phase of jump. There
      were no significant (p > 0.05) main effects of heavy resistance exercise on DJ
      performance variables. Only the biceps femoris during the propulsive phase of the
      DJ was significantly higher (p < 0.05) following HRE compared to no-HRE. Some
      trends in the data were evident and the power of the statistical tests was low.
      It was concluded that no evidence was found to support the experimental
      hypothesis although the absence of a treatment effect could not be ruled out.
      From a practical point of view, undertaking a bout of HRE had no adverse effects
      on subsequent plyometric performance and so some of the advantages of complex
      training still remain.

PMID- 14636091
TI  - Physiological and functional effects of acute low-frequency hand-arm vibration.
AB  - The effects of low frequency of vibration have not been widely studied in the
      scientific literature, yet humans are exposed to such environmental stress
      everyday. The purpose of this investigation was to examine the physiological
      responses to low-frequency upper-body limb vibration. Fourteen healthy men were
      exposed to 1 hour of bilateral hand-arm vibration and control (no vibration)
      conditions in a counter-balanced, cross-over design separated by 2 days. Subjects
      gripped handles that were coupled to a vibrating device, which oscillated in an
      anterior to posterior direction at a constant frequency of 7.5 Hz and a
      displacement of 0.38 cm. A series of tests were performed prior to and following
      the vibration to assess cardiovascular response, visual acuity, tremor of the
      hand and fingers, grip strength, anticipation response, limb girths, and a
      movement repositioning task. There were significantly (p < or = 0.05) more visual
      errors postvibration compared with postcontrol on a standardized vision chart.
      Tremor was significantly reduced during the vibration compared with the control
      condition. There were no significant changes in grip strength. Mean anticipation
      response time was significantly increased during the control condition (+3.3%)
      but not after vibration (+1.0%). There was a significant improvement in the
      movement repositioning task after vibration compared with control. Heart rates
      during the vibration protocol were not significantly higher than the control
      condition. No significant increases in limb size representative of swelling were
      observed. These data indicate that exposure to 1 hour of low-frequency hand-arm
      vibration has only minor effects on physiological function.

PMID- 14636092
TI  - Changes in dynamic exercise performance following a sequence of preconditioning
      isometric muscle actions.
AB  - Complex training is the method of coupling heavy and light loads into an
      organized sequence with the aim of facilitating postactivation potentiation.
      Anecdotal evidence has supported the use of complex training sequences, but
      scientific studies investigating the effects of sequencing isometric loads with
      dynamic muscle actions have been limited. The purpose of this study was to
      examine the effects of a preconditioning sequence of maximal isometric knee
      extensions on performance standards in selected dynamic whole-body exercise.
      Fourteen track and field athletes (23 +/- 5.7 years; 71.53 +/- 6.93 kg; 172.6 +/-
      5.8 cm) were randomly assessed in selected whole-body exercises (drop and
      countermovement jumps, 5-second cycle sprint, knee extension) following a
      sequence of maximal voluntary isometric contractions (MVC; 3 repetitions of 3
      seconds or 3 repetitions of 5 seconds) or in the absence of prior loading
      (control). Electromyographic (EMG) assessments of muscle activity were also made
      during the knee extension assessment. Significant (p < or = 0.05) increases in
      jump height (5.03%), maximal force (4.94%), and acceleration impulse (9.49%) were
      observed in the drop jump following 3 repetitions of 3-second MVC only. Knee
      extension maximal torque was also significantly increased (6.12%) following the 3
      second MVC. No significant changes in countermovement jump or cycle sprint
      measures were observed for any of the experimental conditions. Though adaptations
      were found, changes in EMG activity were not significantly different for any of
      the experimental conditions. These data indicate that performing a sequence of
      repeated maximal isometric knee extensions (3 repetitions of 3 seconds) prior to
      selected dynamic exercise (< or =0.25 seconds) may have favorable effects on
      performance beyond standards achieved without prior heavy loading.

PMID- 14636093
TI  - Postactivation potentiation response in athletic and recreationally trained
      individuals.
AB  - To determine if training status directly impacted the response to postactivation
      potentiation, athletes in sports requiring explosive strength (ATH; n = 7) were
      compared to recreationally trained (RT; n = 17) individuals. Over the course of 4
      sessions, subjects performed rebound and concentric-only jump squats with 30%,
      50%, and 70% 1 RM loads. Jump squats were performed 5 minutes and 18.5 minutes
      following control or heavy load warm-ups. Heavy load warm-up consisted of 5 sets
      of 1 repetition at 90% 1 RM back squat. Jump squat performance was assessed with
      a force platform and position transducer. Heavy load warm-up did not have an
      effect on the subjects as a single sample. However, when percent potentiation was
      compared between ATH and RT groups, force and power parameters were significantly
      greater for ATH (p < 0.05). Postactivation potentiation may be a viable method of
      acutely enhancing explosive strength performance in athletic but not
      recreationally trained individuals. Reference Data: Chiu, L.Z.F., A.C. Fry, L.W.
      Weiss, B.K. Schilling, L.E. Brown, and S.L. Smith. Postactivation potentiation
      response in athletic and recreationally trained individuals.

PMID- 14636094
TI  - Muscle strength assessment from functional performance tests: role of body size.
AB  - The aim of the study was to test the hypothesis that the body size plays an
      important role in assessment of muscle ability to exert force by standard
      functional performance tests. Twenty-one male students were tested on maximal
      isometric lift, one leg rising, vertical jump, and box lift tests, and the
      maximal isokinetic strength of hip and knee extensors was also recorded. When
      indices of the 4 functional performance tests were related to the strength of
      each of the 2 leg extensor muscle groups, only maximal isometric lift
      demonstrated positive correlation with knee extensors strength. When muscle
      strength was corrected for body mass, however, the aforementioned relationship
      became insignificant, but the 1 leg rising performance demonstrated a positive
      relationship with knee extensor strength. In addition, maximal isometric lift and
      1 leg rising test performance provided positive and negative correlation,
      respectively, with body mass. The obtained findings were in line with the effects
      of scale applied on the tested performance. We generally conclude that the
      assessment of muscle capability to exert force based on some standard functional
      performance tests could be confounded by the body size effect.

PMID- 14636095
TI  - Disability levels of college-aged men with a history of Osgood-Schlatter disease.
AB  - Osgood-Schlatter disease (OSD), which is a traction apophysitis of the tibial
      tuberosity, is one of the most common orthopedic conditions that adolescent
      athletes will encounter. Adolescent athletes with OSD typically present with
      pain, swelling, and tenderness over the tibial tuberosity that worsens with
      athletic activity. Few published reports have described the effects of OSD on the
      disability levels of athletes beyond adolescence. Therefore, the purpose of this
      study was to assess the disability levels of college-aged male subjects (n = 25,
      mean age = 20.3 years) who have a history of OSD and compare their status to a
      control group of healthy male subjects with no history of OSD (n = 25, mean age =
      20.4 years) matched by intercollegiate sport and age. The mean time from being
      diagnosed with OSD to participation in this study was 7.6 +/- 2.4 years for
      subjects in the OSD group. All subjects completed the Knee Outcome Survey
      Activities of Daily Living Scale and Sports Activity Scale, which served as our
      measure of disability. The results indicated that subjects with a history of OSD
      scored significantly lower than subjects in the control group on both the Knee
      Outcome Survey Activities of Daily Living Scale and Sports Activity Scale,
      indicating that subjects with OSD experienced higher levels of disability than
      subjects in the control group.

PMID- 14636096
TI  - Effects of delayed onset muscle soreness on selected physiological responses to
      submaximal running.
AB  - This study examined the effects of delayed-onset muscle soreness (DOMS) on
      selected physiological responses to submaximal exercise. Seven male and four
      female subjects (Ss) aged 21-37 years completed two submaximal running sessions
      at an individualized pace corresponding to a blood lactate concentration (bLa) of
      approximately 2.5 mmol x L(-1). Following the first session (T1), Ss performed a
      series of lower extremity resistance exercises designed to induce DOMS. Subjects
      were then retested (T2) 24-30 hours later, during which time all Ss experienced
      DOMS. Oxygen uptake, heart rate (HR), respiratory exchange ratio, rating of
      perceived exertion (RPE), and bLa were measured every 6 minutes. Significant
      trial effects (p < 0.05) were observed for HR and RPE. HR was significantly
      higher during T1 at minutes 6 and 12 (p < 0.05), and RPE values were
      significantly higher at T2 during all recording periods (p < 0.05). Results from
      this study suggest that DOMS does not affect submaximal oxygen uptake. However,
      DOMS does appear to affect one's perception of effort.

PMID- 14636097
TI  - Effect of explosive resistance training on titin and myosin heavy chain isoforms
      in trained subjects.
AB  - The purpose of this investigation was to evaluate changes in myosin heavy chain
      (MyHC) and titin isoforms after using various loads during explosive jump squat
      training. Twenty-four male athletic subjects were recruited for this study. Two
      experimental groups performed 8-weeks of jump squats using either 30% (n = 9) or
      80% (n = 9) of their previously determined 1 repetition maximum. A third group
      served as controls (n = 6). Muscle biopsies were obtained before and after 8
      weeks from vastus lateralis. The analysis of titin within these subjects
      confirmed that human skeletal muscle contains 2 isoforms of titin. There was no
      significant group x time interaction for MyHC or titin isoform expression. The
      data from this investigation indicates that a relatively short period of
      explosive resistance training results in negligible changes in the expression of
      MyHC or titin isoforms.

PMID- 14636098
TI  - Effects of aerobic exercise on strength performance following various periods of
      recovery.
AB  - The purpose of this study was to determine if the type and intensity of aerobic
      training affects performance in a subsequent strength-training session after
      varying periods of recovery. Sixteen male subjects participated in the study and
      were divided into 2 groups based on aerobic training, high-intensity intervals
      (MAX n = 8) and continuous submaximal (SUB n = 8). Each subject performed 4 sets
      of both bench press and leg press at approximately 75% 1 repetition maximum (1RM)
      following aerobic training with recovery periods of 4, 8, and 24 hours, as well
      as once in a control condition. Both the 4- and 8-hour conditions resulted in
      fewer total leg press repetitions than the control and 24-hour conditions. There
      was no difference between both the control and 24-hour conditions. No main effect
      was shown with respect to the type of aerobic training. It was concluded that
      when aerobic training precedes strength training, the volume of work that can be
      performed is diminished for up to 8 hours. This impairment appears to be
      localized to the muscle groups involved in the aerobic training.

PMID- 14636099
TI  - Effect of rest interval length on repeated 1 repetition maximum back squats.
AB  - To examine the effects of different rest intervals on the repeatability of 1
      repetition maximum (1RM) efforts in the free-weight back squat exercise, 17
      weight-trained men served as subjects (mean age 22.0 years). One repetition
      maximum was tested on each of the first 2 days of testing to establish a stable
      baseline (1RM = 184.9 kg). Each of the next 3 sessions involved performing 2 1RM
      back squats, with the rest interval between attempted lifts being either 1, 3, or
      5 minutes, assigned in a counterbalanced fashion. For the 1-minute rest interval,
      13 of 17 subjects successfully completed the second lift; for the 3-minute rest
      interval, 16 of 17 were successful; and for the 5-minute rest interval, 15 of 17
      were successful. Cochran Q analysis determined no significant difference (p >
      0.05) in the ability to repeat a successful maximal-effort back squat when
      different rest intervals were used. These findings are consistent with the
      literature for the bench-press exercise and indicate that 1-minute rest intervals
      are sufficient for recovery between attempted lifts during 1RM testing or
      training for the free-weight back squat when involving lifters of this caliber.

PMID- 14636100
TI  - Effect of knee position on hip and knee torques during the barbell squat.
AB  - Some recommendations suggest keeping the shank as vertical as possible during the
      barbell squat, thus keeping the knees from moving past the toes. This study
      examined joint kinetics occurring when forward displacement of the knees is
      restricted vs. when such movement is not restricted. Seven weight-trained men
      (mean +/- SD; age = 27.9 +/- 5.2 years) were videotaped while performing 2
      variations of parallel barbell squats (barbell load = body weight). Either the
      knees were permitted to move anteriorly past the toes (unrestricted) or a wooden
      barrier prevented the knees from moving anteriorly past the toes (restricted).
      Differences resulted between static knee and hip torques for both types of squat
      as well as when both squat variations were compared with each other (p < 0.05).
      For the unrestricted squat, knee torque (N.m; mean +/- SD) = 150.1 +/- 50.8 and
      hip torque = 28.2 +/- 65.0. For the restricted squat, knee torque = 117.3 +/-
      34.2 and hip torque = 302.7 +/- 71.2. Restricted squats also produced more
      anterior lean of the trunk and shank and a greater internal angle at the knees
      and ankles. The squat technique used can affect the distribution of forces
      between the knees and hips and on the kinematic properties of the exercise.
      PRACTICAL APPLICATIONS: Although restricting forward movement of the knees may
      minimize stress on the knees, it is likely that forces are inappropriately
      transferred to the hips and low-back region. Thus, appropriate joint loading
      during this exercise may require the knees to move slightly past the toes.

PMID- 14636102
TI  - Effects of creatine supplementation and resistance training on muscle strength
      and weightlifting performance.
AB  - Creatine monohydrate has become the supplement of choice for many athletes
      striving to improve sports performance. Recent data indicate that athletes may
      not be using creatine as a sports performance booster per se but instead use
      creatine chronically as a training aid to augment intense resistance training
      workouts. Although several studies have evaluated the combined effects of
      creatine supplementation and resistance training on muscle strength and
      weightlifting performance, these data have not been analyzed collectively. The
      purpose of this review is to evaluate the effects of creatine supplementation on
      muscle strength and weightlifting performance when ingested concomitant with
      resistance training. The effects of gender, interindividual variability, training
      status, and possible mechanisms of action are discussed. Of the 22 studies
      reviewed, the average increase in muscle strength (1, 3, or 10 repetition maximum
      [RM]) following creatine supplementation plus resistance training was 8% greater
      than the average increase in muscle strength following placebo ingestion during
      resistance training (20 vs. 12%). Similarly, the average increase in
      weightlifting performance (maximal repetitions at a given percent of maximal
      strength) following creatine supplementation plus resistance training was 14%
      greater than the average increase in weightlifting performance following placebo
      ingestion during resistance training (26 vs. 12%). The increase in bench press
      1RM ranged from 3 to 45%, and the improvement in weightlifting performance in the
      bench press ranged from 16 to 43%. Thus there is substantial evidence to indicate
      that creatine supplementation during resistance training is more effective at
      increasing muscle strength and weightlifting performance than resistance training
      alone, although the response is highly variable.

PMID- 14636103
TI  - Creatine monohydrate supplementation on body weight and percent body fat.
AB  - Seventeen active males (age 22.9 +/- 4.9 year) participated in a study to examine
      the effects of creatine monohydrate supplementation on total body weight (TBW),
      percent body fat, body water content, and caloric intake. The TBW was measured in
      kilograms, percent body fat by hydrostatic weighing, body water content via
      bioelectrical impedance, and caloric intake by daily food log. Subjects were
      paired and assigned to a creatine or placebo group with a double-blind research
      design. Supplementation was given for 4 weeks (30 g a day for the initial 2 weeks
      and 15 g a day for the final 2 weeks). Subjects reported 2 days a week for
      supervised strength training of the lower extremity. Significant increases before
      and after the study were found in TBW (90.42 +/- 14.74 to 92.12 +/- 15.19 kg) and
      body water content (53.77 +/- 1.75 to 57.15 +/- 2.01 L) for the creatine group (p
      = 0.05). No significant changes were found in percent body fat or daily caloric
      intake in the creatine group. No significant changes were noted for the placebo
      group. These findings support previous research that creatine supplementation
      increases TBW. Mean percent body fat and caloric intake was not affected by
      creatine supplementation. Therefore weight gain in lieu of creatine
      supplementation may in part be due to water retention.

PMID- 14636104
TI  - Effects of effervescent creatine, ribose, and glutamine supplementation on
      muscular strength, muscular endurance, and body composition.
AB  - The purpose of this study was to examine the effects of a combination of
      effervescent creatine, ribose, and glutamine on muscular strength (MS), muscular
      endurance (ME) and body composition (BC) in resistance-trained men. Subjects were
      28 men (age: 22.3 +/- 1.7 years; weight: 85.8 +/- 12.1 kg; height: 1.8 +/- 0.1 m)
      who had 2 or more years of resistance-training experience. A double blind,
      randomized trial was completed involving supplementation or placebo control and a
      progressive resistance-training program for 8 weeks. Dependent measures were
      assessed at baseline and after 8 weeks of resistance training. Both groups
      significantly improved MS and ME while the supplement group significantly
      increased body weight and fat-free mass. Control decreased body fat and increased
      fat-free mass. This study demonstrated that the supplement group did not enhance
      MS, ME, or BC significantly more than control after an 8-week resistance-training
      program.

PMID- 14636105
TI  - Effects of vitamin E supplementation on recovery from repeated bouts of
      resistance exercise.
AB  - The purpose of this study was to examine the effects of vitamin E (VE)
      supplementation (1200 IU/day) on recovery responses to repeated bouts of
      resistance exercise. Non-resistance trained men were assigned to supplement with
      VE (n = 9) or placebo (PL; n = 9) for 3 weeks and then perform 3 resistance
      exercise sessions separated by 3 days of recovery (EX-1, EX-2, and EX-3).
      Performance was assessed at EX-1, EX-2, and EX-3. Fasting morning blood samples
      and perceived muscle soreness were obtained before EX-1 and for 10 consecutive
      days. Muscle soreness peaked after EX-1 and gradually returned to baseline values
      by day 6. Lower and upper body maximal strength and explosive power were
      significantly (p < or = 0.05) decreased at EX-2 and EX-3 (approximately 10%).
      Plasma malondialdehyde (MDA) was significantly elevated on days 7 and 8. There
      were no significant differences between VE and PL in muscle soreness, performance
      measures, or plasma MDA. Creatine kinase (CK) area under the curve from day 1 to
      day 10 was significantly greater for VE because of a nearly 2-fold greater
      increase in CK after EX-1 in VE, compared with PL (404 +/- 146 and 214 +/- 179
      U/L, respectively). VE supplementation was not effective at attenuating putative
      markers of membrane damage, oxidative stress, and performance decrements after
      repeated bouts of whole-body concentric/eccentric resistance exercise.

PMID- 14636106
TI  - Reliability of power output during short-duration maximal-intensity intermittent
      cycling.
AB  - The aims of the present study were: (a) to determine the number of
      familiarization trials required to establish a high degree of reliability in
      measures of power output during maximal intermittent cycling; and (b) to examine
      the reliability of those same measures after familiarization had been
      established. On separate days over a 3-week period, 2 groups of 7 recreationally
      active men completed 8 trials of 1 of 2 maximal (20 x 5-second) intermittent
      cycling tests with contrasting recovery periods (10-seconds or 30-seconds).
      Significant (p < 0.05) between-trial differences were detected in post-hoc tests
      involving trials 1 and 2 only. Within-subject test-retest reliability was
      therefore assessed across trials 3-8. Apart from values of maximum power output
      in Protocol 1 (10-second recovery periods), all remaining measures of power
      output showed high degrees of within-subject test-retest reliability (coefficient
      of variation: 2.4-3.7%). The results of the present study indicate that in
      subjects unfamiliar with maximal intermittent cycling, high degrees of
      reliability in many performance measures can be achieved following the completion
      of 2 familiarization trials.

PMID- 14636107
TI  - Activity profile of young soccer players during actual match play.
AB  - This study investigated the activity profile of young soccer players (mean age
      11.8 +/- 0.6 years; N = 12) with the aim of providing information for the
      development of training strategies. Data for movements of each player were
      obtained using 2 cameras that aimed at the subject throughout the match (Play
      Controller, Phromos, Italy). Encoders transmitted camera movements to a computer.
      The collected signals were then converted into distances, times, and speed
      attained at arbitrarily selected match categories. Players were monitored during
      official 11 vs. 11 matches (N = 12), with each match consisting of 2 halves, each
      lasting 30 minutes played on a regular soccer pitch. Mean total match distance
      amounted to 6,175 +/- 318 m. During the second half, players covered 5.5% less
      distance (p > 0.05). At speeds between 13.1 and 18.0 km.h(-1), players covered
      12% less distance during the second half (p < 0.05). Players stood still 11% of
      the total time played (3,789 +/- 109 seconds). At speeds faster than 18 km.h(-1),
      players performed 33 +/- 4 bouts during match play, with a mean time length of
      2.3 +/- 0.6 seconds per bout. Mean time interval between two successive maximal
      sprint bouts was 118.5 +/- 20.5 seconds. Players stood still longer during the
      course of the second half (229 +/- 76 seconds vs. 173 +/- 61 seconds, p < 0.05).
      Players tended to play in small areas of the football pitch and spent 9% of the
      total match time at high intensity. In order to promote a more active space
      coverage of the young player, at least for the age considered in the present
      study, the dimensions of the football pitch and the number of players should be
      reduced.

PMID- 14636108
TI  - Contributing factors to performance of a medicine ball explosive power test: a
      comparison between jump and nonjump athletes.
AB  - The present study examined the factors contributing to performance of a backward
      overhead medicine ball throw (B-MBT) across 2 types of athletes. Twenty male
      volleyball players (jump athletes) and 20 wrestlers (nonjump athletes) were
      evaluated on 4 measures of power, including B-MBT, chest medicine ball throw (C
      MBT), countermovement vertical jump (CMJ), and power index (PI). The athletes
      also completed 3 measures of strength: a 1-repetition-maximum (1RM) bench press
      (BP), a 1RM leg press (LP), and combined BP + LP strength. Jump athletes
      demonstrated greater absolute scores for CMJ, C-MBT, and B-MBT (p < 0.05),
      whereas nonjump athletes demonstrated greater strength scores for BP and for BP +
      LP (p < 0.05). When performances were examined on a relative basis, jump athletes
      achieved superior scores for C-MBT (p < 0.05), whereas nonjump athletes had
      greater scores for BP, LP, and BP + LP (p < 0.05). For both groups, B-MBT had
      strong correlations with PI (r = 0.817 [jump] and 0.917 [nonjump]), whereas for C
      MBT, only nonjump athletes demonstrated a strong correlation (r = 0.842). When
      expressed in relative terms, B-MBT was strongly correlated with C-MBT (r = 0.762
      [jump] and 0.835 [nonjump]) and CMJ (r = 0.899 [jump] and 0.945 [nonjump]). Only
      nonjump athletes demonstrated strong correlations with strength for absolute LP
      (r = 0.801) and BP + LP (r = 0.810) strength. The interaction of upper- and lower
      body strength and power in the performance of a B-MBT appears complex, with the
      contributing factors differing for athletes with divergent skill sets and
      performance demands.

PMID- 14636109
TI  - Effects of resisted sled towing on sprint kinematics in field-sport athletes.
AB  - Weighted sled towing is a common resisted sprint training technique even though
      relatively little is known about the effects that such practice has on sprint
      kinematics. The purpose of this study was to explore the effects of sled towing
      on acceleration sprint kinematics in field-sport athletes. Twenty men completed a
      series of sprints without resistance and with loads equating to 12.6 and 32.2% of
      body mass. Stride length was significantly reduced by approximately 10 and
      approximately 24% for each load, respectively. Stride frequency also decreased,
      but not to the extent of stride length. In addition, sled towing increased ground
      contact time, trunk lean, and hip flexion. Upper-body results showed an increase
      in shoulder range of motion with added resistance. The heavier load generally
      resulted in a greater disruption to normal acceleration kinematics compared with
      the lighter load. The lighter load is likely best for use in a training program.

PMID- 14636110
TI  - Effect of training in Greco-Roman wrestling on neck strength at the elite level.
AB  - Special training methods in wrestling have been assumed to improve the stability
      and tolerance of the neck. The aim of this study was to measure the neck strength
      levels reached in an extremely physically demanding sport. A neck strength
      measurement system was used to measure various parameters of maximal isometric
      neck strength in Finnish senior wrestlers competing at the international level.
      The results were compared with those achieved by junior wrestlers and a control
      group. The means (SD) of the maximal isometric neck strength for cervical
      rotation were 0.4 (0.1) Nm.kg(-1) for the senior wrestlers, 0.3 (0.1) Nm.kg(-1)
      for the junior wrestlers, and 0.2 (0.1) Nm.kg(-1) for the nonsportsmen. The
      respective results for cervical flexion were 4.4 (1.4), 3.8 (0.7), and 2.3 (0.8)
      Nm.kg(-1); for extension, 6.0 (1.1), 5.9 (0.7), and 4.0 (0.9) Nm.kg(-1). Neck
      strength in flexion seems to improve more than in extension as the result of
      wrestling. The greatest difference was found in rotation, which in the senior
      wrestlers was almost 3 times that in the nonsportsmen. There was great individual
      variation within all groups, and the results revealed weaknesses in all
      directions. Maximal neck strength measurements provide information useful in
      planning training programs to correct possible muscle deficiency and imbalance.

PMID- 14636111
TI  - Maximum strength-power-performance relationships in collegiate throwers.
AB  - Presently the degree to which peak force influences power production or explosive
      performance such as strength training movements or throwing (shot-put and weight
      throw) is unclear. This study describes the relationships between a measure of
      maximum strength, isometric peak force (IPF), dynamic peak force (PF), peak power
      (PP), the 1-repetition movement power snatch (SN), and throwing ability over an 8
      week training period. Five male and 6 female (n = 11) well-trained collegiate
      throwers participated. PF was measured using an AMTI force plate; PP was measured
      using an infrared-ultrasonic tracking device (V-Scope, Lipman Electronics). Clean
      pulls from the midthigh position were assessed isometrically and dynamically at a
      constant load, 30% and 60% of IPF. Specific explosive strength was evaluated
      using an SN and using the shot-put (SP) and weight-throw (WGT) measured under
      meet conditions. Variables (PF, PP, SN) were assessed 3 times at 0 weeks, 4
      weeks, and 8 weeks. Each measurement period preceded a field meet by 3 days. Peak
      force, peak rate of force development, and PP increased over the 8 weeks.
      Correlation coefficients (r) indicate that IPF is strongly related to dynamic PF
      and PP 30%, 60% of the IPF. Furthermore, strong correlations were found for the
      SN and the distance for the SP and WGT, and these relationships tended to
      increase over time. Results suggest that maximum strength (i.e., IPF) is strongly
      associated with dynamic PF. In addition, maximum strength is strongly associated
      with PP even at relatively light loads such as those associated with sport
      specific dynamic explosiveness (i.e., SN, SP, WGT).

PMID- 14636112
TI  - Impact of training patterns on incidence of illness and injury during a women's
      collegiate basketball season.
AB  - This study was conducted to monitor the training patterns throughout a basketball
      season in order to determine if a relationship exists between the physical stress
      of practice and the occurrence of injuries and illnesses in NCAA Division III
      athletes. Subjects consisted of college women (n = 12) ranging in age from 18 to
      22 years. A certified athletic trainer distributed a questionnaire following each
      practice, including 2 weeks of preseason, documenting the presence of injury,
      illness, or both, relative to the intensity and duration of practice. Training
      load, training monotony, and training strain were computed using the session rate
      of perceived exertion scale method. An increase in injuries occurred during times
      of increased training loads, particularly during the first 2 weeks of formal
      practice, and immediately subsequent to the holidays. The temporal relationship
      between training load and injury suggests a causative link (p < 0.01; r = 0.675).
      The present data suggest that the periodization pattern of basketball training
      may be linked to the likelihood of illness/injury.

PMID- 14636113
TI  - Effects of an eight-week training program on upper-body power in women cross
      country skiers.
AB  - A distinguishing feature of elite cross-country skiers is their superlative upper
      body power (UBP). Recently, roller board training was shown to be superior for
      improving UBP in cross-country skiers; however, the newly developed wind machine
      had not yet been tested. The purpose of this study was to determine if wind
      machine training was as effective as roller board training at increasing UBP.
      Forty-four women cross-country skiers, age 23-59 years, were matched on initial
      UBP, measured in watts (W), and placed into 1 of 2 experimental groups (roller
      board or wind machine). All women underwent 8 weeks of UBP training. Although
      both groups improved significantly pre-post (p < 0.05) in UBP, t-tests indicated
      that there was no significant difference (p > 0.05) between the 2 groups'
      improvements (roller board, pre 74.5 +/- 30.9, post 95.9 +/- 29.8 W; wind
      machine, pre 74.5 +/- 33.5, post 99.3 +/- 34.3 W). Thus the wind machine was as
      effective at enhancing UBP as the roller board.

PMID- 14636114
TI  - Effects of physioball and conventional floor exercises on early phase adaptations
      in back and abdominal core stability and balance in women.
AB  - The purpose of this study was to compare the effects of 5 weeks of physioball
      core stability and balance exercises with conventional floor exercises in women.
      The experimental group (n = 15) performed curl-ups and back extensions on the
      physioball while the control group (n = 15) performed the same exercises on the
      floor. Baseline and post-training tests included electromyography (EMG)
      recordings of the rectus abdominus and erector spinae muscles; abdominal, back,
      and knee strength measurements with the Cybex Norm System; and 2 unilateral
      stance balance tests. The physioball group was found to have significantly
      greater mean change in EMG flexion and extension activity (p = 0.04 and p = 0.01,
      respectively) and greater balance scores (p < 0.01) than the floor exercise
      group. No significant changes (p > 0.05) were observed for heart rate or Cybex
      strength measurements. Early adaptations in a short-term core exercise program
      using the physioball resulted in greater gains in torso balance and EMG neuronal
      activity in previously untrained women when compared to performing exercises on
      the floor.

PMID- 14636115
TI  - Resistance training exercises acutely reduce intraocular pressure in physically
      active men and women.
AB  - Our purpose was to examine the effect of the chest press and leg press exercises
      on intraocular pressure (IOP) in physically active, college-aged students.
      Fifteen healthy males and 15 females performed 3 sets of 10 repetitions of the
      chest press or leg press with 70% 1 repetition maximum (1RM). IOP was measured
      using applanation tonometry with a Tono-PenXL prior to exercise, following each
      set and 5 minutes after the third set. Data were analyzed with a repeated
      measures two-way analysis of variance and paired t-tests when necessary. A p <
      0.05 was accepted as statistically significant. For the chest press, IOP was
      reduced 8.0% after the first set, up to 14.5% after the second and third sets,
      and remained depressed 5 minutes post exercise. For the leg press, IOP was
      reduced 6.9% after the second set and 13.2% after the third set. IOP began to
      return to the pre-exercise value during 5 minutes post exercise. Males and
      females had similar IOP responses to the chest press and leg press exercise.
      Dynamic resistance exercises induce modest postexercise decreases in IOP.

PMID- 14636117
TI  - Wealth, poverty and climate change.
AB  - Rich countries must lead the fight against climate change affecting rich and poor
      in our global village.

PMID- 14636118
TI  - Health and foreign policy: scope for Australian engagement?

PMID- 14636119
TI  - What drives the NHS?

PMID- 14636120
TI  - Snowballing obesity: Australians will get run over if they just sit there.
AB  - Overweight and obesity are very common in Australian adults (56%) and children
      (27%). Rates of overweight and obesity are snowballing and will place greater
      burdens on health services for the treatment and care of chronic diseases.
      Prevention is urgently required from health, social and economic perspectives,
      but the response to date has been inadequate. A long-term, sustained action plan
      starting with a focus on young people is needed. This should particularly address
      the "obesogenic" environments causing the epidemic. Although whole-of-government
      action is required, support from and involvement by parents, carers, community
      leaders, healthcare professionals, teachers, childcare workers, urban planners,
      recreation managers, food manufacturers, employers, advertisers, and
      communicators is essential. The health sector should take the lead, but success
      will only come from concerted and integrated action across the whole of society.
      There are now signs of political commitment to addressing overweight and obesity.
      Doctors should get behind this and help mobilise community support.

PMID- 14636121
TI  - Waist-hip ratio is the dominant risk factor predicting cardiovascular death in
      Australia.
AB  - OBJECTIVE: To evaluate clinical measures of obesity for their ability to predict
      death from cardiovascular disease (CVD) and coronary heart disease (CHD), in
      parallel with conventional cardiovascular risk factors. DESIGN, PARTICIPANTS AND
      SETTING: Cross-sectional analysis of an age- and sex-stratified sample of 9206
      adults aged 20-69 years from Australian capital cities (1989 Australian Risk
      Factor Prevalence Survey). Blood pressure, fasting serum lipid levels, smoking,
      history of heart disease or diabetes, and obesity as measured by body mass index
      (BMI), waist circumference and waist-hip ratio were recorded. These data were
      linked with the National Death Index to determine causes of death of the 473
      survey subjects who had died to 31 December 2000. MAIN OUTCOME MEASURES: Hazard
      ratios for the risk factors predicting CVD mortality and CHD mortality. RESULTS:
      Of the modifiable risk factors, obesity, as measured by waist-hip ratio, is a
      dominant, independent, predictive variable for CVD and CHD deaths in Australian
      men and women. Self-reported angina/myocardial infarction in both sexes, and
      cigarette smoking in women, are also independent risk factors. CONCLUSIONS:
      Obesity assessed by waist-hip ratio is a better predictor of CVD and CHD
      mortality than waist circumference, which, in turn, is a better predictor than
      BMI. The recognition of central obesity is clinically important, as lifestyle
      intervention is likely to provide significant health benefits.

PMID- 14636123
TI  - Epidemic of diabetes in China.

PMID- 14636122
TI  - The costs of weight control: what do young women pay?

PMID- 14636125
TI  - An Afghanistan experience.

PMID- 14636124
TI  - Medical practice on the front line: separating the myths from the reality.

PMID- 14636126
TI  - A richer tapestry of many identities.

PMID- 14636127
TI  - From Beirut to Sydney: backyards, breast cancer, and basic opportunity.

PMID- 14636128
TI  - An Australian with a Chinese face.

PMID- 14636129
TI  - Across two continents and a century: the tale of two doctors.
AB  - Two generations of Santoros have served the Italian community of Melbourne for
      over 70 years.

PMID- 14636130
TI  - Bench-to-bedside research in Australian research institutes: a snapshot.

PMID- 14636131
TI  - Nobel Prizes for magnetic resonance imaging and channel proteins.

PMID- 14636132
TI  - Research within a medical degree: the combined MB BS-PhD program at the
      University of Sydney.
AB  - Along with its new graduate-entry medical program, the University of Sydney has
      introduced the Combined Degree (Research) Program which allows students to
      graduate with an MB BS and PhD. The program includes 2-3 years of full-time
      research between Years 2 and 3 of the 4-year MB BS program. The program aims to
      produce clinician-scientists committed to continuing research that reflects their
      experience of clinical practice. Eight women and 23 men have enrolled since the
      program began in 1998, with the first cohort graduating in 2003. The students
      have been active in helping to develop the program and establishing a society and
      other student support networks.

PMID- 14636133
TI  - Stemming the tide of river blindness: the early years of ivermectin.

PMID- 14636134
TI  - Paper bullets of the brain. A neurologist's story.

PMID- 14636135
TI  - Three years of "CASMS": the world's busiest medical simulation centre.
AB  - Medical simulation is a relatively new teaching modality suitable for medical
      education at all levels, although its long-term benefits have not yet been
      validated. Simulation allows the participant to practise diagnosis, medical
      management and behavioural approaches in the care of acutely ill patients in a
      controlled environment. Simulators have achieved widespread acceptance in the
      fields of anaesthesia, intensive care and emergency medicine. More recently, team
      training for pre-hospital and within-hospital multidisciplinary medical response
      teams has become popular. The increasing number and diversity of courses at
      "CASMS" parallels the evolution of simulation centres into regional clinical
      skills centres elsewhere. Such centres are likely to become a cost-effective
      means of achieving greater consistency in medical skill acquisition and may
      improve patient outcomes after medical crises.

PMID- 14636136
TI  - A "multilemma" for doctors.

PMID- 14636137
TI  - The Fiji School of Medicine postgraduate training project.

PMID- 14636138
TI  - Australian Doctors' Orchestra: mixing music and medicine.

PMID- 14636139
TI  - Of miracle cures and murderous doctors.
AB  - Do the media promote, for the sake of entertainment, unrealistic hopes and
      exaggerated fears of doctors?

PMID- 14636140
TI  - Media reporting of specific mental illnesses in the context of crime:
      implications for mental health literacy.

PMID- 14636141
TI  - An analysis of newspaper reports of cancer breakthroughs: hope or hype?
AB  - OBJECTIVE: To assess the importance of cancer "breakthroughs" reported in the
      popular media 10 years after their publication. STUDY DESIGN: Questionnaire-based
      survey in 2003 of expert opinion on the importance of all alleged cancer
      "breakthroughs" in cancer research or treatment reported in news articles in The
      Sydney Morning Herald between 1992 and 1994. MAIN OUTCOME MEASURES: Assessment of
      each "breakthrough" by an expert in the relevant cancer subspecialty on seven
      measures of current importance. RESULTS: 31 unique reports of alleged cancer
      "breakthroughs" were identified, and experts responded to questionnaires on 30.
      Thirteen of these 30 reports (43%) were judged as not having been supported by
      further research in the following decade, with three (10%) having been refuted,
      while 16 (53%) were judged to remain potential breakthroughs, but more research
      was required. Eight "breakthroughs" (27%) had, or would soon be, incorporated
      into practice. CONCLUSION: Cancer research findings reported in newspapers as
      "breakthroughs" are often not true breakthroughs but may be important for ongoing
      research. Consumers are likely to be receiving an overly optimistic picture of
      progress in understanding and treating cancer.

PMID- 14636142
TI  - Healthy Skepticism's new AdWatch: understanding drug promotion.
AB  - The AdWatch section of the Healthy Skepticism website
      (http://www.healthyskepticism.org/adwatch.asp) aims to improve medical decision
      making by illuminating the techniques used in drug advertising. AdWatch draws on
      20 years of dialogue about drug promotion plus ideas from many disciplines,
      especially logic, psychology and marketing.

PMID- 14636143
TI  - Feeling at home in an emergency: coping with death in the emergency department.

PMID- 14636144
TI  - Death in the emergency department: a not so absolutely ordinary rainbow.

PMID- 14636145
TI  - Measuring the immeasurable.

PMID- 14636146
TI  - The homeless and the emergency department: a special relationship.

PMID- 14636147
TI  - What's in a name? The dangers of the unknown in the emergency department.

PMID- 14636148
TI  - Another cause of "Irukandji stingings".

PMID- 14636149
TI  - Sublingual glyceryl trinitrate as prehospital treatment for hypertension in
      Irukandji syndrome.

PMID- 14636150
TI  - Is four a deadly number for the Chinese?
AB  - BACKGROUND: The numbers 4, 14 and 24 are associated with death for Cantonese
      speaking Chinese people, as the words for these numbers sound like the words for
      "death", "must die" and "easy to die", respectively. A previous study in the
      United States investigating psychological stress engendered by fear of the number
      4 found more cardiac deaths in Chinese and Japanese people, compared with white
      Americans, on the 4th day of the month. OBJECTIVE: To determine whether more
      cardiac deaths occur in Hong Kong Chinese people on the days of the month with
      "deathly connotations" (4, 14 and 24). DESIGN: Analysis of mortality data (1995
      2000) of the Chinese population of Hong Kong from the Census and Statistics
      Department of the Hong Kong Government for these three days of the month,
      compared with the remaining days, according to both the Gregorian and Lunar
      calendars. RESULTS: There were 17 346 cardiac deaths registered under ICD-9 codes
      410-414 in 1995-2000. The mean (+ 1 SD) of the cumulative number of cardiac
      deaths on each day of the month was 587 (+ 30) for the Gregorian calendar or 573
      (+ 24) for the Lunar calendar. The mean number of deaths on the 4th, 14th and
      24th day of the month was not significantly different from the mean number of
      deaths on the remaining days of the month. CONCLUSION: Our study of Hong Kong
      Chinese people does not support the concept that more cardiac deaths occur in
      Cantonese people on the 4th, 14th and 24th day of the month.

PMID- 14636151
TI  - Interns are from Venus, consultants are from Mars: differential perception among
      clinicians.
AB  - OBJECTIVE: To test for the presence of sex-based differences in perception (the
      notion that men and women "think" differently, and that differences in perception
      are biologically based) among healthcare professionals. DESIGN: Prospective
      survey. SETTING AND PARTICIPANTS: 90 medical personnel at a tertiary care
      hospital in Newcastle, NSW. INTERVENTION: Healthcare professionals were shown two
      pictures that could be interpreted as depicting either a young or an old person,
      and a word that could be seen as geometric shapes. MAIN OUTCOME MEASURES: The
      effects of sex, age, seniority, and specialisation in relation to the first
      impression of the image, the ability to change one's perception, and the speed of
      perception. RESULTS: Contrary to popular opinion, male physicians were more
      likely to perceive the older figures, and just as likely as women to be able to
      change their perception. Surgeons and junior staff were more likely to see, as
      well as being faster to form, an impression requiring abstract thought, and were
      more able to change their perceptions. CONCLUSIONS: Traditional sex stereotypes
      do not apply to medical personnel, but other age-based stereotypes, and
      professional rivalries (medical versus surgical) may have some empiric basis.

PMID- 14636152
TI  - Political correctness in the modern hospital, or, PC in 2003.

PMID- 14636153
TI  - There is such a thing as a free lunch?

PMID- 14636154
TI  - Second trimester Doppler ultrasound screening of the uterine arteries
      differentiates between subsequent normal and poor outcomes of hypertensive
      pregnancy: two different pathophysiological entities?
AB  - The 'classical' concept that pregnancy-induced hypertension (PIH) and pre
      eclampsia (PE) primarily originate from defective placentation in early pregnancy
      has been challenged recently. There is growing evidence that other factors,
      including maternal predisposing conditions, also play a significant role in the
      pathophysiology of PIH and PE. The aim of the present study was to test the
      hypothesis that PIH and PE with an early onset and poor pregnancy outcome is
      associated with defective placentation, e.g. inadequate spiral artery dilatation
      and subsequent reduced uteroplacental perfusion, whereas PIH and PE with normal
      pregnancy outcome is not. Using Doppler ultrasound, we measured the uterine
      artery pulsatility index (PI) in a population of 531 nulliparous women in the
      22nd week of gestation. Uterine artery PI was used as an index of resistance to
      blood flow in the uteroplacental circulation. Outcome measures were PIH/PE with
      or without poor pregnancy outcome, preterm birth and intra-uterine growth
      restriction (IUGR). The results revealed a striking difference between PI values
      for PIH/PE with and without poor pregnancy outcome. Uterine artery PI in the 22nd
      week was increased significantly in pregnancies which developed early-onset
      (before 35 weeks) PIH/PE with a poor pregnancy outcome. In contrast, uterine
      artery PI values were normal in women who developed PIH/PE, but had a good
      pregnancy outcome. There was a significant correlation between 22nd week uterine
      artery PI and subsequent preterm birth or IUGR. Our results indicate that only
      PIH/PE with poor pregnancy outcome is associated with defective placentation,
      whereas PIH/PE with good outcome is not. These findings support the concept of
      heterogeneous causes of hypertensive disorders of pregnancy.

PMID- 14636155
TI  - Assessment of the longitudinal and circumferential left ventricular function at
      rest and during exercise in healthy elderly individuals by tissue-Doppler
      echocardiography: relationship with heart rate.
AB  - Tissue-Doppler echocardiography (TDE) has been introduced to quantify stress
      echocardiography by means of assessing the left ventricular (LV) segmental
      myocardial velocities and excursion. The interaction between LV long- and short
      axis function during physical exercise has not been elucidated completely. The
      aim of the present study was to investigate long- and short-axis LV function, as
      assessed by myocardial velocities and excursions at rest and during exercise and
      its possible relationship with heart rate in healthy elderly individuals by TDE.
      Twenty-seven individuals underwent an exercise test in the supine position on a
      bicycle ergometer. The initial workload was 30 Watts, followed by 20-Watt
      increments every third minute. Standard echocardiographic images with super
      imposed colour TDE were digitized at the end of each step. The following
      variables were studied in the LV long- and short-axis: myocardial peak systolic
      velocity (PSV) and excursion, isovolumic contraction and relaxation times, peak
      velocity at early diastole (E'-wave) and peak velocity at late diastole (A'-wave)
      and the E'/A' ratio. Increments in myocardial peak systolic velocity and
      excursion in the LV long-axis were more pronounced during low workloads. The
      increase in those variables in the short-axis occurred mainly at higher exercise
      loads. The improvement in LV long- and short-axis functions was closely related
      to the increase in the heart rate. Shortening of the isovolumic contraction and
      relaxation times occurred only at the initial stages of exercise. An increase in
      the long-axis E'/A' ratio occurred during exercise, whereas this ratio was
      unchanged in the short-axis. In conclusion, during exercise, the LV long- and
      short-axis functions behave differently, and increases in LV long- and short-axis
      functions are related to changes in heart rate. Therefore, in the interpretation
      of echocardiographic findings during exercise stress echocardiography, these
      facts have to be taken into account.

PMID- 14636156
TI  - Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric
      adenocarcinoma.
AB  - The aim of the present study was to investigate the prevalence of c-FLIP
      [cellular FLICE-inhibitory protein, where FLICE is Fas-associated death domain
      (FADD)-like interleukin-1beta-converting enzyme] expression in gastric
      adenocarcinoma and its possible implications for the progression of the cancer.
      Expression of c-FLIP in 48 gastric adenocarcinomas and their normal counterparts
      was analysed by reverse transcriptase PCR, Western blotting and
      immunohistochemistry. In situ cell apoptosis was detected by TUNEL (terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. As a
      result, c-FLIP transcripts were constitutively expressed in gastric
      adenocarcinomas and their levels were significantly higher than those in matched
      normal tissues ( P < 0.01). Immunohistochemically, the c-FLIP protein was also
      found to be expressed in all gastric adenocarcinomas (48/48), and 68.8% (33/48)
      showed an intense immunostaining; in contrast, only 75% (36/48) of normal gastric
      mucosa showed positive staining and none of them immunostained intensely. The
      abundance of c-FLIP protein was significantly higher in carcinoma than in normal
      gastric mucosa (6.93 +/- 0.58 versus 3.19 +/- 0.26, P < 0.01) and showed a
      reverse correlation with apoptotic index in adenocarcinoma, but not in normal
      mucosa. In addition, abundance of c-FLIP was significantly associated with lymph
      node metastasis at both mRNA level ( P < 0.05) and protein level ( P < 0.01).
      Western-blot analysis showed that the expression levels of the long form of c
      FLIP and the short form of c-FLIP in adenocarcinomas were 2.6-fold and 2.8-fold (
      P < 0.01) higher than those in normal tissues respectively. However, no
      significant difference was found between the expression levels of the two
      isoforms in both adenocarcinomas or normal tissues. In conclusion, overexpression
      of c-FLIP is tumour specific, which may be one of the in vivo mechanisms by which
      tumour cells escape from apoptotic death during the malignant transformation, and
      plays an important role in lymph node metastasis of gastric adenocarcinoma, which
      ultimately contributes to the tumour progression.

PMID- 14636158
TI  - Cy5 maleimide labelling for sensitive detection of free thiols in native protein
      extracts: identification of seed proteins targeted by barley thioredoxin h
      isoforms.
AB  - Barley thioredoxin h isoforms HvTrxh1 and HvTrxh2 differ in temporal and spatial
      distribution and in kinetic properties. Target proteins of HvTrxh1 and HvTrxh2
      were identified in mature seeds and in seeds after 72 h of germination.
      Improvement of the established method for identification of thioredoxin-targeted
      proteins based on two-dimensional electrophoresis and fluorescence labelling of
      thiol groups was achieved by application of a highly sensitive Cy5 maleimide dye
      and large-format two-dimensional gels, resulting in a 10-fold increase in the
      observed number of labelled protein spots. The technique also provided
      information about accessible thiol groups in the proteins identified in the
      barley seed proteome. In total, 16 different putative target proteins were
      identified from 26 spots using tryptic in-gel digestion, matrix-assisted laser
      desorption ionization-time-of-flight MS and database search. HvTrxh1 and HvTrxh2
      were shown to have similar target specificity. Barley alpha-amylase/subtilisin
      inhibitor, previously demonstrated to be reduced by both HvTrxh1 and HvTrxh2, was
      among the identified target proteins, confirming the suitability of the method.
      Several alpha-amylase/trypsin inhibitors, some of which are already known as
      target proteins of thioredoxin h, and cyclophilin known as a target protein of m
      type thioredoxin were also identified. Lipid transfer protein, embryospecific
      protein, three chitinase isoenzymes, a single-domain glyoxalase-like protein and
      superoxide dismutase were novel identifications of putative target proteins,
      suggesting new physiological roles of thioredoxin h in barley seeds.

PMID- 14636157
TI  - Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex
      of the 26 S proteasome in fast-twitch skeletal muscles.
AB  - Circulating levels of glucocorticoids are increased in many traumatic and muscle
      wasting conditions that include insulin-dependent diabetes, acidosis, infection,
      and starvation. On the basis of indirect findings, it appeared that these
      catabolic hormones are required to stimulate Ub (ubiquitin)-proteasome-dependent
      proteolysis in skeletal muscles in such conditions. The present studies were
      performed to provide conclusive evidence for an activation of Ub-proteasome
      dependent proteolysis after glucocorticoid treatment. In atrophying fast-twitch
      muscles from rats treated with dexamethasone for 6 days, compared with pair-fed
      controls, we found (i) increased MG132-inhibitable proteasome-dependent
      proteolysis, (ii) an enhanced rate of substrate ubiquitination, (iii) increased
      chymotrypsin-like proteasomal activity of the proteasome, and (iv) a co-ordinate
      increase in the mRNA expression of several ATPase (S4, S6, S7 and S8) and non
      ATPase (S1, S5a and S14) subunits of the 19 S regulatory complex, which regulates
      the peptidase and the proteolytic activities of the 26 S proteasome. These
      studies provide conclusive evidence that glucocorticoids activate Ub-proteasome
      dependent proteolysis and the first in vivo evidence for a hormonal regulation of
      the expression of subunits of the 19 S complex. The results suggest that
      adaptations in gene expression of regulatory subunits of the 19 S complex by
      glucocorticoids are crucial in the regulation of the 26 S muscle proteasome.

PMID- 14636159
TI  - Comparative analysis of DNA methylation patterns in transgenic Drosophila
      overexpressing mouse DNA methyltransferases.
AB  - DNA methyltransferases (Dnmts) mediate the epigenetic modification of eukaryotic
      genomes. Mammalian DNA methylation patterns are established and maintained by co
      operative interactions among the Dnmt proteins Dnmt1, Dnmt3a and Dnmt3b. Owing to
      their simultaneous presence in mammalian cells, the activities of individual Dnmt
      have not yet been determined. This includes a fourth putative Dnmt, namely Dnmt2,
      which has failed to reveal any activity in previous assays. We have now
      established transgenic Drosophila strains that allow for individual
      overexpression of all known mouse Dnmts. Quantitative analysis of genomic
      cytosine methylation levels demonstrated a robust Dnmt activity for the de novo
      methyltransferases Dnmt3a and Dnmt3b. In addition, we also detected a weak but
      significant activity for Dnmt2. Subsequent methylation tract analysis by genomic
      bisulphite sequencing revealed that Dnmt3 enzymes preferentially methylated CpG
      dinucleotides in a processive manner, whereas Dnmt2 methylated isolated cytosine
      residues in a non-CpG dinucleotide context. Our results allow a direct comparison
      of the activities of mammalian Dnmts and suggest a significant functional
      specialization of these enzymes.

PMID- 14636160
TI  - Protein aggregation in motor neurone disorders.
AB  - Toxicity associated with abnormal protein folding and protein aggregation are
      major hypotheses for neurodegeneration. This article comparatively reviews the
      experimental and human tissue-based evidence for the involvement of such
      mechanisms in neuronal death associated with the motor system disorders of X
      linked spinobulbar muscular atrophy (SBMA; Kennedy's disease) and amyotrophic
      lateral sclerosis (ALS), especially disease related to mutations in the
      superoxide dismutase (SOD1) gene. Evidence from transgenic mouse, Drosophila and
      cell culture models of SBMA, in common with other trinucleotide repeat expansion
      disorders, show protein aggregation of the mutated androgen receptor, and
      intraneuronal accumulation of aggregated protein, to be obligate mechanisms.
      Strong experimental data link these phenomena with downstream biochemical events
      involving gene transcription pathways (CREB-binding protein) and interactions
      with protein chaperone systems. Manipulations of these pathways are already
      established in experimental systems of trinucleotide repeat disorders as
      potential beneficial targets for therapeutic activity. In contrast, the evidence
      for the role of protein aggregation in models of SOD1-linked familial ALS is less
      clear-cut. Several classes of intraneuronal inclusion body have been described,
      some of which are invariably present. However, the lack of understanding of the
      biochemical basis of the most frequent inclusion in sporadic ALS, the
      ubiquitinated inclusion, has hampered research. The toxicity associated with
      expression of mutant SOD1 has been intensively studied however. Abnormal protein
      aggregation and folding is the only one of the four major hypotheses for the
      mechanism of neuronal degeneration in this disorder currently under investigation
      (the others comprise oxidative stress, axonal transport and cytoskeletal
      dysfunctions, and glutamatergic excitotoxicity). Whilst hyaline inclusions, which
      are strongly immunoreactive to SOD1, are linked to degeneration in SOD1 mutant
      mouse models, the evidence from human tissue is less consistent and convincing. A
      role for mutant SOD1 aggregation in the mitochondrial dysfunction associated with
      ALS, and in potentially toxic interactions with heat shock proteins, both leading
      to apoptosis, are supported by some experimental data. Direct in vitro data on
      mutant SOD1 show evidence for spontaneous oligomerization, but the role of such
      oligomers remains to be elucidated, and therapeutic strategies are less well
      developed for this familial variant of ALS.

PMID- 14636161
TI  - Class I MHC detection as a diagnostic tool in noninformative muscle biopsies of
      patients suffering from dermatomyositis (DM).
AB  - This study is to further confirm the diagnostic value of class I MHC detection in
      muscle biopsies of adult patients presenting with clinical features of
      dermatomyositis (DM) and to address its diagnostic value in the case of
      nonspecific biopsies. A retrospective study was performed on muscle biopsies in
      22 patients presenting with clinical features of DM. Immunohistochemical
      detection of class I MHC was performed in all cases. On pathological features two
      groups of patients were recorded: group I (14 patients) with typical features of
      DM and group II (eight patients) with almost normal muscle biopsies (no
      inflammatory exudates, no perifascicular atrophy). Abnormal sarcolemmal class I
      MHC expression was recorded in all cases. In all muscle biopsies of group I
      patients, class I MHC expression was observed in almost all fibres but was
      stronger in perifascicular areas (eight patients) or was restricted to
      perifascicular atrophic fibres (six patients). In all muscle biopsies of group II
      patients, only some perifascicular fibres expressed class I MHC. According to
      Bohan and Peter criteria, patients were classified as definite DM (nine group I
      and three group II patients), probable DM (five group I and two group II
      patients) and possible DM (three group II patients). Abnormal perifascicular
      class I MHC expression is of diagnostic value in patients presenting with
      clinical features of DM especially when muscle biopsy fails to show typical
      features such as inflammatory infiltrates and/or perifascicular atrophy.

PMID- 14636162
TI  - Role of interferon-gamma and nitric oxide in the neuropathogenesis of avirulent
      Semliki Forest virus infection.
AB  - Semliki Forest virus (SFV) infection of mice provides a useful model for the
      analysis of viral neuropathogenesis. In this study, the roles of interferon (IFN)
      gamma and nitric oxide (NO) in the pathogenesis of SFV infection were assessed
      using mice deficient in inducible nitric oxide synthase (iNOS-/-), an enzyme
      important in the production of NO, and mice deficient in IFN-gamma receptor (IFN
      gammaR-/-). Gene-knockout and wildtype mice were infected intranasally with the
      avirulent A7 strain of SFV and neuropathological lesions were correlated with
      levels of IFN-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10
      in the olfactory bulbs and frontal cortex. Lesions in IFN-gammaR-/- mice were
      characterized by higher levels of neuronal necrosis than in wildtype mice. The
      higher levels of neuronal necrosis were associated with increased levels of SFV
      antigen in neurones and increased numbers of macrophages and B cells. Relative
      differences in the severity of demyelination between IFN-gammaR-/- and wildtype
      mice were not detected. Similar levels of neuronal necrosis and SFV antigen
      labelling occurred in iNOS-/- mice and wildtype mice and levels of demyelination
      and macrophage infiltration in the iNOS-/- mice were lower than those in the
      wildtype strain. A rapid, but transient increase in the concentration of IFN
      gamma was demonstrated in the frontal cortex of all infected mice samples. IL-10
      levels in the frontal cortex and olfactory bulbs of SFV-infected iNOS-/- mice
      exceeded those present in the wildtype mice. This study, taken with our previous
      reports, provides further evidence that type 1 T cell responses are important in
      the control of brain viral clearance and the prevention of neuronal necrosis, but
      not in the development of demyelination.

PMID- 14636163
TI  - Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by
      subarachnoid injection of Microfil.
AB  - There is mounting evidence that a significant portion of cerebrospinal fluid
      drainage is associated with transport along cranial and spinal nerves with
      absorption taking place into lymphatic vessels external to the central nervous
      system. To characterize these pathways further, yellow Microfil was infused into
      the cisterna magna of 2-7-day-old lambs post mortem to perfuse either the cranial
      or spinal subarachnoid compartments. In some animals, blue Microfil was perfused
      into the carotid arteries simultaneously. Microfil was observed in lymphatic
      networks in the nasal mucosa, covering the hard and soft palate, conchae, nasal
      septum, the ethmoid labyrinth and the lateral walls of the nasal cavity. Many of
      these lymphatics drained into vessels located on the lateroposterior wall of the
      nasopharynx and from this location drained to the retropharyngeal lymph nodes.
      Additionally, lymphatics containing Microfil penetrated the lateral wall of the
      nasal cavity and joined with superficial lymphatic ducts travelling towards the
      submandibular and preauricular lymph nodes. In two cases, lymphatic vessels were
      observed anastomosing with deep veins in the retropharyngeal area. Microfil was
      also distributed within the nerve trunks of cranial and spinal nerves. The
      contrast agent was located in longitudinal channels within the endoneurial space
      and lymphatics containing Microfil were observed emerging from the mesoneurium.
      In summary, Microfil distribution patterns in neonatal lambs illustrated the
      important role that cranial and spinal nerves play in linking the subarachnoid
      compartment with extracranial lymphatics.

PMID- 14636164
TI  - CDKN2A, CDKN2B and p14ARF are frequently and differentially methylated in
      ependymal tumours.
AB  - Ependymal tumours are histologically and clinically varied lesions. Numerical
      abnormalities of chromosome 9 are frequently associated with these tumours.
      Nevertheless, the three important tumour suppressor genes located in this
      chromosome, CDKN2A, CDKN2B and p14 ARF, have not been reported to be commonly
      altered in them. We studied promoter methylation of these genes, an important
      mechanism associated with gene silencing in a series of 152 ependymal tumours of
      WHO grades I to III. Methylation status of the CDKN2A, CDKN2B and p14 ARF
      promoters was assessed by methylation-specific polymerase chain reaction and the
      genetic results were correlated to clinicopathological features. We observed
      promoter methylation for CDKN2A in 21% (26/123) of tumours, for CDKN2B in 32%
      (23/71) and p14 ARF in 21% (23/108). For all three genes, posterior fossa
      ependymomas were less frequently methylated in paediatric patients than in
      adults. For CDKN2B, extracranial tumours were more frequently methylated than
      intracranial ones. For CDKN2B and p14 ARF, methylation was more frequent in low
      grade tumours; the reverse was observed for CDKN2A. CDKN2A, CDKN2B and p14 ARF
      promoters were methylated in 21-32% of the tumours. Frequencies of methylation
      varied according to clinicopathological features. This suggests a role for these
      genes in ependymoma tumorigenesis.

PMID- 14636165
TI  - Chemokine receptors on infiltrating leucocytes in inflammatory pathologies of the
      central nervous system (CNS).
AB  - Haematogenous leucocytes enter the central nervous system (CNS) during diverse
      disorders of varied aetiologies. Understanding the trafficking cues that mediate
      CNS leucocyte infiltration might promote the development of flexible and
      selective means to modulate inflammation to achieve clinical benefit. The
      trafficking machinery of leucocytes has been elucidated during the past decade
      and consists of cell-surface adhesion molecules, chemoattractant cytokines
      (chemokines) and their receptors. Recent work in our laboratory characterized
      chemokine receptors found on T lymphocytes and monocytes in brain sections from
      subjects with one pathological subtype of multiple sclerosis (MS), an immune
      mediated inflammatory demyelinating disease. In these tissues, the types 1 and 5
      CC chemokine receptors (CCR1 and CCR5) were detected on perivascular monocytic
      cells whereas only CCR5 was present on parenchymal macrophages. The type 3 CXC
      chemokine receptor (CXCR3) was present on virtually all CD3-positive T cells. In
      the current study, we evaluated the expression of these receptors on the
      infiltrating cells present in cases of other inflammatory CNS disorders including
      those of dysimmune, infectious, neoplastic, and vascular aetiology. Perivascular
      and parenchymal monocytic cells expressed CCR1 in all cases and CXCR3 was
      consistently present on a substantial proportion of CD3+ T cells. The occurrence
      of CCR5 on parenchymal macrophages was much less uniform across the varied
      disorders. These data implicate CCR1 in monocyte infiltration of the CNS and are
      consistent with reports of studies in CCR1-deficient mice. CXCR3 is also likely
      to play a role in accumulation of T cells in the inflamed CNS. By contrast, our
      findings suggest that regulation of CCR5 on phagocytic macrophages may be
      contingent on the lesion environment.

PMID- 14636166
TI  - Stereotactic co-registration of magnetic resonance imaging and histopathology in
      post-mortem multiple sclerosis brain.
AB  - A number of groups have examined the pathological substrate of signal changes on
      magnetic resonance imaging (MRI) in post-mortem (PM) brain of patients with
      multiple sclerosis (MS). Such studies will benefit from using a standardized
      method to reliably co-register regions of interest on MRI and tissue specimens.
      We investigated the usefulness of a stereotactic navigation system for this
      purpose. We also addressed the sensitivity of different standard MRI sequences
      with regard to lesion conspicuity in PM MS brain. Post-mortem brains of eight
      patients with MS were studied. Formalin-fixed coronal slices were placed in the
      head frame of a stereotactic system. Proton density-, T2-weighted and fast fluid
      attenuated inversion recovery (FLAIR) scans were obtained and visually matched
      with scans that had been previously obtained on the same, but fresh, specimens.
      Guided by the stereotactic target points, the dissection of the fixed specimens
      was performed. After processing the blocks for embedding in paraffin, sections
      were stained with haematoxylin-eosin and Luxol fast blue. T2-weighted MRI of
      fixed brain revealed 24 areas suspected to be MS lesions, all of which were
      confirmed histologically. Three of these lesions were not visible on macroscopic
      inspection. There were 14 additional hyperintensities on T2-weighted or FLAIR MRI
      of the fresh specimens, five of which did not correlate to MS lesions
      histologically. Stereotactic navigation is a useful approach to co-register MRI
      and histopathology in PM brain of MS patients and may improve the precision of
      MRI-guided sampling of tissue specimens. Standard T2-weighted MRI appeared to be
      the single most useful approach for lesion detection in fresh and fixed
      specimens.

PMID- 14636167
TI  - Prion protein accumulation involving the peripheral nervous system in a sporadic
      case of Creutzfeldt-Jakob disease.

PMID- 14636171
TI  - Maternal genotype influences stress reactivity of vasopressin-deficient
      brattleboro rats.
AB  - The role of vasopressin, cosecreted with corticotropin-releasing hormone (CRH),
      in stress is debated, because both normal as well as reduced adrenocorticotropin
      hormone (ACTH) rise to an acute challenge has been reported in Brattleboro rats
      genetically lacking vasopressin (di/di). Because di/di pups could be born either
      from di/+ (heterozygous) or from di/di mothers, and maternal influence is known
      to modify adult responsiveness, we investigated whether the influence of maternal
      genotype could explain the variability. Adult rats from mothers with different
      genotypes were stressed with 60 min restraint and trunk blood was collected for
      measuring hormone content by radioimmunoassay at the end of stress. All offspring
      of di/+ mothers had similar ACTH responses to restraint, while the di/di rats
      born to, and raised by di/di mothers showed reduced ACTH reactivity to restraint.
      The di/di rats showed elevated water turnover and required a daily cage cleaning
      every day, which meant frequent handling. To offset the role of handling, all
      rats had daily cage cleaning in the next series, but the results were the same as
      in the first series. To investigate whether lactation, the behaviour of the
      mother or some other factor during the pregnancy is responsible for the
      differences, pups from di/+ dams were raised by di/di foster mothers and vice
      versa. We found that the genotype of parental mother is more important than that
      of the foster mother. The corticosterone and prolactin elevation normally seen
      after acute stress was unchanged by family history, maternal or personal
      genotype. Furthermore, in studies with mutant animals, the rearing conditions
      should be controlled by the experimenter. In experiments with Brattleboro rats,
      the use of homozygous and heterozygous rats from the same litters of di/+ dams
      and di/di males is recommended. Our results suggest that vasopressin is not
      indispensable for ACTH release, and that the di/di genotype of the parental
      mother can decrease the stress reactivity of the di/di Brattleboro rats.

PMID- 14636172
TI  - Phagocytosis of Candida albicans and superoxide anion Levels in ring dove
      (Streptopelia risoria) heterophils: effect of melatonin.
AB  - We observed in previous studies on avian heterophils that incubation with either
      physiological or pharmacological concentrations of the neurohormone melatonin
      increased the phagocytosis of inert particles (latex beads), and also provoked a
      decline in superoxide anion levels of those phagocytes. In the present study, we
      wanted to corroborate whether melatonin acts on the oxidative metabolism that
      accompanies the respiratory burst during phagocytosis by inducing a more
      effective phagocytic activity at the same time as exerting an antioxidant effect
      to eliminate and/or scavenge the free radicals left over after the destruction of
      the foreign material. To this end, we evaluated the ingestion and destruction of
      Candida albicans (live particles) by ring dove (Streptopelia risoria) heterophils
      after different times of incubation (30 and 60 min) with physiological
      concentrations of melatonin (50 pg/ml diurnal and 300 pg/ml nocturnal), as well
      as with a pharmacological concentration 23 x 106 pg/ml (100 micro m) of the
      hormone. In parallel, using the same times of incubation, we evaluated the
      oxidative metabolism by determining the superoxide anion levels (O2-.). The
      results show that melatonin, at all the times and concentrations studied,
      increases both the phagocytosis index (number of C. albicans phagocytosed by 100
      heterophils) and the candidicide power (percentage of C. albicans killed of those
      ingested by 100 heterophils). The effect was dose-dependent. With respect to the
      oxidative metabolism accompanying the digestion and destruction, there was a
      decline in superoxide anion levels after incubation with all of the
      concentrations of the hormone studied. The effect was dose-dependent and most
      pronounced at 60 min. These results thus corroborate the proposal that melatonin
      enhances the phagocytic function at the same time as neutralizing the oxidative
      stress derived from this immune function.

PMID- 14636173
TI  - Effects of agouti-related protein on metabolism and hypothalamic neuropeptide
      gene expression.
AB  - The hypothalamic melanocortin system regulates feeding in part through
      interaction of the appetite stimulating peptide, agouti-related protein (AGRP),
      and the anorectic peptide, alpha-melanocyte stimulating hormone, a peptide
      derived from the pro-opiomelanocortin (POMC) polyprotein. Central administration
      of AGRP induces hyperphagia and increased gain in body weight in rodents, but may
      also exert metabolic effects even when hyperphagia is prevented. In the present
      studies, the effects of AGRP on hypothalamic neuropeptide gene expression and
      metabolism were examined in the rat. Central administration of AGRP for 3- and 7
      day periods resulted in hyperphagia, increased body weight and increased plasma
      leptin and insulin concentrations compared to saline-injected controls.
      Hypothalamic concentrations of Pomc mRNA were also increased by 27% and 44% (in 3
      and 7-day experiments, respectively). The hypothalamic concentration of Agrp
      mRNA was unchanged after 3 days, but was significantly decreased by 33% after 7
      days of AGRP infusion. To determine if these changes were dependent upon AGRP
      induced hyperphagia, pair-fed rats with restricted food intake receiving central
      administration of AGRP were also studied. In the absence of hyperphagia,
      intracerebralventricular administration of AGRP caused significant increases in
      plasma leptin and insulin concentrations (two-fold and 1.5-fold, respectively)
      and fat pad mass. A significant increase in hypothalamic Pomc mRNA concentrations
      was not detected in pair-fed rats. In contrast, Agrp mRNA concentrations remained
      suppressed by 45% in the pair-fed group after 7 days of AGRP infusion despite
      equal body weight compared to saline controls. The ratio of hypothalamic Pomc to
      Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats,
      which is consistent with increased stimulation of central melanocortin signalling
      pathways. Thus, central administration of AGRP exerts changes in hypothalamic
      neuropeptide gene expression and metabolic effects that are independent of the
      effects on food intake and body weight.

PMID- 14636174
TI  - Monoaminergic activity in subregions of raphe nuclei elicited by prior stress and
      the neuropeptide corticotropin-releasing factor.
AB  - Corticotropin-releasing factor (CRF) coordinates neuroendocrine responses to
      stressful stimuli; one mechanism through which CRF may modulate hypothalamic
      pituitary-adrenal axis activity is via actions on neuromodulatory systems such as
      serotonergic systems. Recent electrophysiological studies and the distribution of
      CRF receptors within midbrain and pontine raphe nuclei suggest that stress and
      CRF may have actions on topographically organized subpopulations of serotonergic
      neurones. We compared the effects of vehicle or intracerebroventricular r/hCRF
      injections (0, 0.1, 1 or 10 micro g) in rats previously maintained in home cages
      or restrained for 1 h, 24 h before injection, on monoamine and monoamine
      metabolite tissue concentrations in the dorsal (lateral wings, rostral midline,
      caudal midline), median (rostral, caudal) and interfascicular raphe subdivisions
      of the midbrain and pontine raphe nuclei, using brain microdissection and high
      performance liquid chromatography with electrochemical detection. At the lowest
      dose studied (0.1 micro g), CRF infusions in previously stressed rats decreased 5
      hydroxytryptophan (5-HTP) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations
      only within the rostral median raphe nucleus. At higher doses, CRF infusions in
      previously stressed rats increased tissue concentrations of 5-HTP, serotonin (5
      HT), or the serotonin metabolite, 5-HIAA, within rostral (but not caudal) regions
      of the median and dorsal raphe nuclei. By contrast, restraint stress alone had no
      effect on tissue concentrations of 5-HTP, 5-HT or 5-HIAA measured 24 h later in
      any subdivision, while CRF injections in rats not previously exposed to restraint
      stress, with few exceptions, also had no effect. These results suggest that the
      effects of CRF on serotonergic function are context-dependent, dose-dependent,
      and regionally specific within subdivisions of the brainstem raphe nuclei.

PMID- 14636175
TI  - Evidence from studies on co-cultures of TtT/GF and AtT20 cells that Annexin 1
      acts as a paracrine or juxtacrine mediator of the early inhibitory effects of
      glucocorticoids on ACTH release.
AB  - Annexin 1 (ANXA1) is a key mediator of the inhibitory effects of glucocorticoids
      on adrenocorticotropic hormone (ACTH) release, which develop within 1-2 h of a
      steroid challenge. Our previous studies, which showed that (i) ANXA1 is expressed
      principally by the nonsecretory folliculo-stellate cells in the pituitary gland;
      (ii) glucocorticoids cause the exportation of ANXA1 from these cells; and (iii)
      corticotrophs express specific ANXA1 binding sites, led us to propose that ANXA1
      serves as a paracrine or juxtacrine mediator of glucocorticoids. To address this
      hypothesis, we examined ANXA1-dependent glucocorticoid actions in co-cultures of
      murine corticotroph (AtT20 clone D1) and folliculo-stellate (TtT/GF) cell lines.
      ANXA1 mRNA and protein were found in abundance in TtT/GF cells but neither was
      detectable in the AtT20 cells. AtT20 cells (alone and in co-culture with TtT/GF
      cells) responded to corticotropin-releasing hormone (CRH) (0.1-1 micro m) with
      increased ACTH release. The CRH-stimulated release of ACTH from AtT20 cells
      cultured alone was unaffected by preincubation with dexamethasone (Dex, 100 nm);
      by contrast, in co-cultures of AtT20 and TtT/GF cells, the steroid readily
      inhibited the secretory response to CRH. The effects of Dex on ACTH release were
      mimicked by N-terminal ANXA1 fragments (ANXA1Ac2-26, 2 micro g/ml and ANXA11-188,
      0.1 ng/ml) and reversed by mifepristone (1 micro m) and by an antisense
      oligodeoxynucleotide (ODN) to ANXA1 (50 nm) but not by control ODNs. The
      antisense ODN also specifically blocked the Dex-induced externalization of ANXA1
      from TtT/GF cells. Immunofluorescence imaging of the co-cultures localized the
      exported protein to the vicinity of the AtT20 cells and identified ANXA1 binding
      sites on these cells. These results provide functional and histological evidence
      to support our premise that the early inhibitory effects of glucocorticoids on
      ACTH release are dependent upon paracrine/juxtacrine actions of ANXA1 derived
      from folliculo-stellate cells.

PMID- 14636176
TI  - The diurnal modulation of hormonal responses in the rat varies with different
      stimuli.
AB  - The circadian clock, located in the suprachiasmatic nuclei (SCN) of the
      hypothalamus not only controls the basal daily temporal organization of many
      neuroendocrine functions, but also its responsiveness. We studied the time-of-day
      influence on plasma changes in adrenocorticotropic hormone (ACTH),
      corticosterone, glucagon and leptin concentrations elicited by an insulin-induced
      hypoglycaemic event. Male Wistar rats were exposed to an insulin challenge at six
      different times during the light/dark cycle. The time-of-day of exposure markedly
      affected the responses of all four hormones studied. Generally, the magnitude of
      the different hormone responses correlated with their basal daily release pattern
      (i.e. the responses of ACTH and corticosterone were largest around lights off,
      and glucagon and leptin responses were most pronounced during the dark period).
      With regard to the hormones of the hypothalamic-pituitary-adrenal axis, the
      presently reported time-of-day dependent modulation is completely opposite to
      that previously reported for novelty or restraint. Therefore, these findings
      provide further support for the existence of at least two different neural
      pathways that are able to activate the hypothalamic-pituitary-adrenal axis, and
      provide different substrates for modulation by the biological clock. This
      observation warrants a thorough examination of possible functional explanations
      for the observed differences.

PMID- 14636177
TI  - The Hormone Domain of the Vasopressin Prohormone is Required for the Correct
      Prohormone Trafficking Through the Secretory Pathway.
AB  - It has long been known that under intracellular conditions vasopressin associates
      tightly to neurophysin, which is present in the same prohormone. As the
      association has been suggested to play a role during hormone biosynthesis, its
      role was studied in a cellular context by expressing mutant vasopressin
      precursors in Neuro2A cells. Mutant vasopressin precursors, in which the
      association between the vasopressin and neurophysin domains was prevented either
      by deleting the vasopressin domain from the precursor or by substitution of the
      essential Tyr2 residue in vasopressin for Gly, were neither processed nor
      targeted into secretory granules. Rather, both provasopressin mutants were
      retained in the endoplasmic reticulum. Our results demonstrate that the
      vasopressin domain is crucial for correct trafficking of the prohormone through
      the secretory pathway, and suggest that vasopressin-neurophysin association
      provides correct prohormone folding in the endoplasmic reticulum.

PMID- 14636178
TI  - Oestrogen receptor-alpha and -beta immunoreactivity in gonadotropin-releasing
      hormone neurones after ovariectomy and chronic exposure to oestradiol.
AB  - Oestradiol exerts negative- and positive-feedback actions on luteinizing hormone
      (LH) secretion by modulating gonadotropin-releasing hormone (GnRH) release.
      Furthermore, a chronic increase in circulating oestradiol in either young
      ovariectomized (OVX) rats, or in middle-aged persistent oestrous (PE) rats,
      causes a gradual attenuation of LH surges until the positive-feedback action of
      oestradiol disappears. Based on these findings, and on the equivocal evidence
      regarding a direct action of oestradiol on GnRH neurones, we tested the
      hypothesis that chronic oestradiol abolishes LH surges by decreasing the
      proportion of GnRH neurones containing oestrogen receptor (ER)alpha or beta.
      Regularly cycling rats were ovariectomized, and half immediately received
      oestradiol. Three days, or 2 or 4 weeks later, rats were perfused at 18.00 h, and
      GnRH was colocalized with ERalpha or ERbeta by immunocytochemistry. ERbeta was
      expressed in 76% of GnRH neurones, whereas virtually no GnRH cells were
      immunopositive for ERalpha. The proportion of GnRH cells expressing ERalpha or
      beta in OVX rats was not altered by oestradiol or time after OVX, and this was
      the case regardless of their medial to lateral, or rostral to caudal location.
      The results indicate that the mechanisms for the positive-feedback action of
      oestradiol, and the loss of LH surges in OVX rats after chronic oestradiol, are
      not mediated by changes in the proportion of oestrogen-receptor containing GnRH
      neurones.

PMID- 14636179
TI  - Adenosine A2A receptor gene disruption provokes marked changes in melanocortin
      content and pro-opiomelanocortin gene expression.
AB  - A2A receptor knockout (A2AR-/-) mice are more anxious and aggressive, and exhibit
      reduced exploratory activity than their wild-type littermates (A2AR+/+). Because
      alpha-melanocyte-stimulating hormone (alpha-MSH) influences anxiety,
      aggressiveness and motor activity, we investigated the effect of A2AR gene
      disruption on alpha-MSH content in discrete brain regions and pro
      opiomelanocortin (POMC) expression in the hypothalamus and pituitary. No
      modification in alpha-MSH content was observed in the hypothalamus and medulla
      oblongata where POMC-expressing perikarya are located. In the arcuate nucleus of
      the hypothalamus, POMC mRNA levels were not affected by A2AR disruption.
      Conversely, in A2AR-/- mice, a significant increase in alpha-MSH content was
      observed in the amygdala and cerebral cortex, two regions that are innervated by
      POMC terminals. In the pars intermedia of the pituitary, A2AR disruption provoked
      a significant reduction of POMC mRNA expression associated with a decrease in
      alpha-MSH content. By contrast, in the anterior lobe of the pituitary, a
      substantial increase in POMC mRNA and adrenocorticotropin hormone concentrations
      was observed, and plasma corticosterone concentration was significantly higher in
      A2AR-/- mice, revealing hyperactivity of their pituitary-adrenocortical axis.
      Together, these results suggest that adenosine, acting through A2A receptors, may
      modulate the release of alpha-MSH in the cerebral cortex and amygdala. The data
      also indicate that A2A receptors are involved in the control of POMC gene
      expression and biosynthesis of POMC-derived peptides in pituitary melanotrophs
      and corticotrophs.

PMID- 14636181
TI  - Puberty: a period of both organizational and activational effects of steroid
      hormones on neurobehavioural development.
AB  - During perinatal development, steroid hormones act on the central nervous system
      (CNS) to organize neural circuits. These circuits remain relatively dormant until
      hormonal stimulation received in adulthood acts on the CNS to activate adult
      reproductive physiology and behaviour. In this review, the proposal is put
      forward that, in addition to perinatal development, puberty serves as another
      period of neural maturation mediated by both steroid-dependent and -independent
      events that further organize and shape the behavioural potential of the adult
      organism. In support of this thesis, data are summarized that clearly show the
      organizational effects of the pubertal rise in gonadal hormones on mating
      behaviour and other steroid-mediated behaviours exhibited in adulthood, and on
      the neural pathways that mediate these behaviours. The importance of determining
      whether this sensitive period of neural development during puberty is a 'critical
      period' is also discussed, as well as whether perturbations of the nervous system
      during pubertal development may result in negative behavioural and physiological
      outcomes in adulthood. It is concluded that puberty is not merely a time when
      increasing levels of gonadal steroids activate the neural circuits organized
      during perinatal development, but also a time of further organization of the CNS,
      which allows for appropriate behaviours to emerge in adulthood.

PMID- 14636180
TI  - The inhibition of inducible nitric oxide synthase reverts arthritic-induced
      decrease in pituitary growth hormone mRNA but not in liver insulin-like growth
      factor I mRNA expression.
AB  - Experimental arthritis induced by Freund-adjuvant administration is a model of
      chronic inflammation and rheumatoid arthritis associated with a decrease in
      pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I)
      gene expression. Excessive nitric oxide (NO) synthesis by inducible NO synthase
      (iNOS) has been implicated in the pathogenesis of inflammatory illness. Moreover,
      NO participates in the regulation of GH secretion at both the hypothalamus and
      the pituitary. We have examined the role of iNOS activation in producing the
      changes in the GH-IGF-I axis in arthritic rats. Adult male Wistar rats received
      aminoguanidine or vehicle from day 20, after adjuvant or vehicle injection, until
      day 28. Two hours and 30 min after the last aminoguanidine injection, all rats
      were killed by decapitation. Arthritis increased hypothalamic expression of
      somatostatin mRNA while it decreased pituitary GH mRNA expression, and both
      effects were prevented by aminoguanidine administration. In arthritic rats, the
      parallel decrease in serum IGF-I, and in hepatic IGF-I content and mRNA
      expression, correlates with the decrease in circulating GH concentrations.
      Aminoguanidine administration to arthritic rats did not modify either serum GH or
      serum IGF-I concentrations, or hepatic IGF-I mRNA expression. However,
      aminoguanidine administration to control rats resulted in a decrease in serum GH
      concentrations and in a decrease in both hepatic IGF-I mRNA expression and serum
      IGF-I concentrations. These data suggest that NO mediates the arthritis-induced
      decrease in GH mRNA expression by acting at a hypothalamic level, but it is not
      involved in the decrease in hepatic IGF-I mRNA expression.

PMID- 14636182
TI  - Microbiology's principle of biofilms as a major factor in the pathogenesis of
      acne vulgaris.
AB  - Propionibacterium acnes reside within the pilosebaceous unit in a biofilm. As
      such, they live in a community of bacteria that encase themselves within an
      extracellular polysaccharide lining, which the organisms secrete after adherence
      to the surface. This gylcocalyx polymer acts as a protective exoskeleton and
      serves as a physical barrier, limiting effective antimicrobial concentrations
      within the biofilm microenvironment. The gylcocalyx polymer secreted by P. acnes
      as a biofilm may explain the immunogenicity of the organism as well as the
      clinical course of the disease. The P. acnes' biofilm model explains many aspects
      of acne pathogenesis and therapy, including why prolonged antibiotic treatment is
      needed, why antibiotic resistance is not a reliable assessment of treatment
      outcome, why accutane offers long-lasting effectiveness, and why benzoyl peroxide
      radicals are beneficial. This microbiologic principle of biofilms as applied to
      acne leads to numerous new pathways of assessment and exploration.

PMID- 14636183
TI  - Atrophying tinea versicolor: a clinical and histological study of 12 patients.
AB  - BACKGROUND: We describe 12 patients with an atrophying dermatitis in whom the
      biopsy findings were compatible with tinea versicolor. DESIGN: We encountered 12
      skin biopsies from 12 patients in whom a clinically atrophying dermatosis was
      associated with light microscopic (LM) evidence of atrophy and epidermal
      colonization by Pityrosporum sp. Formalin-fixed, paraffin-embedded tissue
      sections were cut at 5 microns and stained with H&E, alcian blue-PAS and PAS
      diastase preparations. RESULTS: Five men and seven women aged 17-73 years in whom
      lesions characterized as atrophic plaques, patches or macules prompted clinical
      differential diagnoses including parapsoriasis or mycosis fungoides (MF),
      anetoderma, lupus erythematosus, and steroid atrophy. A LM examination showed
      epidermal colonization with pityrosporum hyphae and spores accompanied by
      variable epidermal and dermal atrophy characterized by rete-ridge effacement,
      subepidermal fibroplasia, pigment incontinence and elastolysis. CONCLUSIONS:
      Atrophying cutaneous lesions comprise part of the clinical spectrum of tinea
      versicolor for which we propose the term 'atrophying tinea versicolor'. The
      pathogenetic basis is unclear but could be the sequela of delayed type
      hypersensitivity and the release by T-helper lymphocytes of leukotrienes which
      perturb collagen metabolism and/or keratinocyte growth. Lesions may be mistaken
      clinically for MF or other atrophying dermatoses.

PMID- 14636184
TI  - Evaluation of clinical types of cutaneous lichen planus in anti-hepatitis C virus
      seronegative and seropositive Nigerian patients.
AB  - BACKGROUND: The presentation of oral lichen planus in anti-hepatitis C virus
      (HCV) seropositive and seronegative patients was previously evaluated, and the
      keratotic form of oral lichen planus was found to be more prevalent in anti-HCV
      seropositive patients. This study evaluated the presentation of cutaneous lichen
      planus in anti-HCV seropositive and seronegative Nigerians. METHODS: Fifty-seven
      Nigerians with cutaneous lichen planus were carefully examined to determine the
      form of lichen planus present. All were screened for the presence of anti-HCV by
      second-generation enzyme-linked immunosorbent assay (ELISA) and grouped as anti
      HCV seropositive or anti-HCV seronegative patients. RESULTS: Nine patients were
      anti-HCV positive. Seven of these seropositive patients had hypertrophic lichen
      planus. CONCLUSION: Hypertrophic lichen planus in Nigerians is more prevalent
      with HCV infection.

PMID- 14636185
TI  - A revisit of sickle cell disease, sickle cell trait, and the extra transverse
      digital crease on the fingers.
AB  - BACKGROUND: Alteration in the location and number of palmar creases has been
      found in association with certain disorders. The extra transverse digital crease
      (ETDC) has been reported in sickle cell disease. This study was carried out to
      determine the importance of ETDC as a diagnostic tool for sickle cell disease
      amongst Nigerians. METHODS: Medical students and student nurses with available
      hemoglobin electrophoresis records were studied. Their palms were examined for
      the presence of ETDC. RESULTS: An ETDC was present in 80 of 178 (44.9%) cases
      with genotype AA, 26 of 68 (38.2%) cases with sickle cell trait (AS, 65; AC, 3),
      and 10 of 22 (45.4%) cases with sickle cell disease (SS). CONCLUSIONS: The
      results from our study show that the ETDC is not a diagnostic sign of sickle cell
      disease in Nigerians.

PMID- 14636186
TI  - Lymph node involvement in Jorge Lobo's disease: report of two cases.

PMID- 14636187
TI  - Congenital agminated nevi on the trunk.

PMID- 14636188
TI  - Extensive xanthelasma associated with anaplastic large cell lymphoma and
      hyperimmunoglobulin E syndrome.

PMID- 14636189
TI  - Solitary embolic cutaneous aspergillosis in the immunocompromised patient with
      acute myelogenous leukemia - a propos another case caused by Aspergillus flavus.

PMID- 14636190
TI  - Multiple, keratoacanthoma-like nodules on a 47-year-old man: a rare presentation
      of cutaneous lupus erythematosus.

PMID- 14636191
TI  - Cutaneous malignant fibrous histiocytoma of the face.

PMID- 14636192
TI  - Puzzling penile papules.

PMID- 14636193
TI  - Mucoepidermoid carcinoma (adenosquamous carcinoma) treated with Mohs micrographic
      surgery.
AB  - BACKGROUND: Mucoepidermoid carcinoma (MEC), sometimes referred to as
      adenosquamous carcinoma (ASC), is a common malignant tumor of the salivary glands
      that can also develop from the esophagus, lacrimal passages, lung, upper
      respiratory tract, pancreas, prostate and thyroid. Rarely, MEC will present
      primarily in the skin. CASE: We present a case of primary MEC of the lower eyelid
      treated successfully with Mohs micrographic surgery. RESULTS: Mohs micrographic
      surgery was performed because of the highly aggressive and unpredictable nature
      of this tumor. The tumor was completely excised using Mohs with negative margins
      achieved in three stages. The patient has been disease free for 3 years since the
      surgery. CONCLUSION: We offer Mohs as an option for treating MEC.

PMID- 14636194
TI  - Clinical and economic impact of Apligraf for the treatment of nonhealing venous
      leg ulcers.
AB  - BACKGROUND: Controlled studies have shown that Apligraf(R) (Organogenesis Inc.,
      Canton, USA) is more economical and more effective at healing venous leg ulcers
      (VLUs) than compression therapy alone. However, the clinical and economic impact
      of Apligraf on healing VLUs in clinical practice has not been fully examined.
      METHODS: A medical chart review was conducted of patients who were treated with
      Apligraf for one or more nonhealing VLUs over a 2-year period at the Henry Ford
      Hospital. Following Apligraf treatment, patients were followed for up to 9
      months. Primary clinical outcome measures were mean change in baseline ulcer size
      (cm2) per week and percent reduction in baseline ulcer size at final study visit.
      Economic evaluation of Apligraf treatment was based on VLU-related medical care
      costs (US$) in relation to ulcer size (cm2) changes before and after Apligraf
      therapy. RESULTS: Thirteen patients with 21 chronic VLUs were treated with
      Apligraf. All had at least one comorbidity, most commonly hypertension (38%).
      Twelve patients were known to have had a prior history of VLU. At baseline, mean
      ulcer duration was 23.9 months and median ulcer size was 13.5 cm2; for the 6
      months preceding Apligraf treatment, in which patients received conventional
      compression therapy, mean ulcer size increased +0.72 cm2 per week. During the
      Apligraf post-treatment study period, mean ulcer size decreased by -2.37 cm2 per
      week. At final clinic visit, ulcers exhibited an average 60.5% reduction in
      baseline size; 21 ulcers (n = 13) showed 75% or greater reduction in size,
      compared with baseline. Economic data were available for five patients; among
      these individuals ulcer-related medical costs per unit change in ulcer size were
      lower following Apligraf treatment relative to such costs with conventional
      compression therapy applied during the Apligraf pretreatment period. CONCLUSIONS:
      In a clinical practice setting, Apligraf is more effective and more economical at
      healing VLUs than conventional therapy alone.

PMID- 14636195
TI  - Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid,
      antioxidants, and sunscreen in the treatment of melasma.
AB  - BACKGROUND: Melasma, also known as mask of pregnancy, is a common, acquired
      hypermelanosis seen in women with Fitzpatrick skin types II-V, and is often
      recalcitrant to treatment with depigmentation agents. Glycolic acid has been
      added to hydroquinone formulations in the past to enhance their depigmentation
      effects, but may cause irritation, leading to postinflammatory hyperpigmentation.
      AIM: To assess the safety and efficacy of a cream containing 4% hydroquinone, 10%
      buffered glycolic acid, vitamins C and E, and sunscreen (Glyquin, ICN
      Pharmaceuticals, Costa Mesa, USA) vs. a cream containing sunscreen alone in the
      depigmentation of epidermal melasma of the face. METHODS: Thirty-nine Hispanic
      women, Fitzpatrick skin types III-V, with bilateral epidermal melasma were
      enrolled in a randomized controlled trial lasting 12 weeks. Patients underwent
      twice-daily full-face application with the study cream or with the cream
      containing sunscreen only. Changes in pigmentation were measured using a
      mexameter, the melasma area and severity index (MASI), and a global evaluation by
      the patient and blind investigator. Safety evaluations were performed at each
      follow-up visit. RESULTS: Thirty-five patients completed the trial. Irritation
      was more common with the study cream, but resolved with temporary cessation of
      cream application and the addition of moisturizers. Mexameter results
      demonstrated a significant decrease in the degree of pigmentation using the study
      cream compared with the cream containing sunscreen alone (P < 0.0001). Fifteen of
      20 patients (75%) using the study cream improved, whereas only two of 15 patients
      (13%) improved using sunscreen alone. CONCLUSIONS: A cream containing 4%
      hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen is safe
      and effective in the treatment of melasma.

PMID- 14636196
TI  - Treatment of pediculosis capitis with thiabendazole: a pilot study.
AB  - BACKGROUND: Despite the improvement of health standards, head lice infestation
      remains a problem worldwide. In addition, there is increasing evidence that head
      lice are becoming resistant to common pediculocides. AIM: To test the potential
      effectiveness of thiabendazole, a potent and broad-spectrum antiparasitic and
      scabicidal agent, for the treatment of pediculosis capitis. METHODS: Twenty-three
      female patients, aged 7-12 years, who had active head lice infestation, were
      treated with oral thiabendazole, 20 mg/kg twice daily for 1 day, with repeat
      treatment after 10 days. RESULTS: On the 11th day, meticulous hair examination
      showed that 21 patients had responded to treatment [91%; 95% confidence interval
      (CI), 71-98%], with 14 showing complete responsiveness (61%; 95% CI, 40-78%). The
      only adverse reactions observed were nausea and mild dizziness, which occurred in
      four patients, three of whom took the drug on an empty stomach. CONCLUSIONS:
      Thiabendazole may be a promising treatment for head lice infestation. The primary
      action of this drug seems to be the inhibition of parasite microtubule
      polymerization by binding to beta-tubulin. In addition, thiabendazole may
      interfere with the synaptic transmission of lice through its probable cholinergic
      effect. As pediculosis capitis is a very communicable disease, the
      unresponsiveness to thiabendazole could largely be attributed to new infestations
      during the drug-free interval. Therefore, massive and simultaneous rather than
      individual and isolated treatments should be used to achieve the epidemiologic
      control of this ectoparasitosis. As this is a preliminary study, the performance
      of double-blind, randomized controlled trials on this subject is warranted.
      Thiabendazole, either alone or in combination with other agents, may prove to be
      of particular use in areas in which head lice show resistance to common
      pediculocides.

PMID- 14636197
TI  - Casanova and venereology.
AB  - In 1750 Casanova met Henriette de Bourbon-Conti, Duchess of Chartres, in Paris.
      She was suffering from a disfiguring syphilis. He prescribed an unusual treatment
      and noticed a transient improvement. But skin disorders rapidly recurred. A few
      years later the young aristocrat died.

PMID- 14636198
TI  - CAM in dermatology: telling fact from fiction.

PMID- 14636199
TI  - Mild pemphigus foliaceus responding to combination therapy with niacinamide and
      tetracycline.

PMID- 14636201
TI  - Clinical utility of ANCA tests for the dermatologist.

PMID- 14636202
TI  - Vascular endothelial growth factor levels are increased and associated with
      disease activity in patients with Behcet's syndrome.
AB  - BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a cytokine
      participating in inflammation with potent endothelial cell effects. It is
      produced by macrophages, neutrophils and vascular endothelial cells and can alter
      vessel permeability. Behcet's syndrome is a systemic inflammatory disorder with
      unknown etiology. Vascular endothelial dysfunction is one of the prominent
      features of the disease. We previously demonstrated the possible involvement of
      proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, soluble interleukin
      2 receptor (sIL-2R), interleukin (IL)-6 and IL-8], nitric oxide (NO) and
      adrenomedullin in the etiopathogenesis of Behcet's syndrome. Since VEGF
      expression is induced by these cytokines and VEGF itself is a potent stimulator
      of NO production with endothelial cell effects, this study aimed to investigate
      whether VEGF was affected during the course of Behcet's syndrome. We also
      assessed the possible involvement of VEGF in ocular Behcet's syndrome or in
      disease activity. METHODS: This multicenter case-control study included a total
      of 39 patients with active (n = 22) or inactive (n = 17) Behcet's syndrome (mean
      age, 38.1 +/- 10.4 years; 21 men and 18 women) satisfying International Study
      Group criteria, and 15 healthy hospital-based control volunteers (mean age, 39.2
      +/- 9.3 years; eight men and seven women) matched for age and gender from a
      similar ethnic background. Patients were examined by a dermatologist and an
      ophthalmologist with an interest in Behcet's syndrome. Plasma VEGF concentrations
      were measured using a newly established enzyme-linked immunosorbent assay.
      Clinical findings and acute-phase reactant parameters such as erythrocyte
      sedimentation rate, alpha1-antitrypsin, alpha2-macroglobulin, and neutrophil
      count were used to classify the disease in Behcet's patients as active or
      inactive. The Wilcoxon test or the Mann-Whitney U-test was used for statistical
      analysis as indicated and the results were expressed as mean +/- SD, with range.
      RESULTS: The mean plasma VEGF level in patients with Behcet's syndrome (291.9 +/-
      97.1 pg/mL; range 121-532 pg/mL) was higher than that in control subjects (103.0
      +/- 43.6 pg/mL; range 25-187 pg/mL) and the difference was significant (P <
      0.001). Patients with active disease had significantly (P < 0.001) higher VEGF
      levels than patients with inactive disease (347.6 +/- 87.1 vs. 219.9 +/- 51.6
      pg/mL). In addition, ocular Behcet's patients (n = 23) had higher VEGF levels
      (315.7 +/- 92.1 pg/mL) than nonocular patients (n = 16, 257.8 +/- 96.6 pg/mL) and
      the difference was of borderline significance (P = 0.041). The levels of all
      acute-phase reactant parameters were significantly higher in the active stage
      than in the inactive stage (for each, P < 0.01) or in control subjects (for each,
      P < 0.001). CONCLUSIONS: VEGF may participate in the course of Behcet's syndrome,
      especially in the active stage, and elevated levels of VEGF may be an additional
      risk factor for the development of ocular disease, contributing to poor visual
      outcome.

PMID- 14636203
TI  - Incidence determinants of gonorrhea, chlamydial genital infection, syphilis and
      chancroid in attendees at a sexually transmitted disease clinic in Athens,
      Greece.
AB  - OBJECTIVE: To determine the specific impact on the incidence rate of some
      demographic and behavioral characteristics in outpatients with four bacterial
      sexually transmitted diseases (STDs). STUDY DESIGN: A cross-sectional hospital
      outpatient-based study was conducted from 1990 to 1996 on 1064 consecutive
      symptomatic STD cases (Chlamydia trachomatis, n = 375; gonorrhea, n = 369; early
      symptomatic syphilis, n = 288, and chancroid, n = 32) using a standardized
      questionnaire. RESULTS: In a reference STD population of 5831 symptomatic
      outpatients, the relative incidence of gonorrhea, syphilis and chancroid was
      found to be increased among immigrants. Low educational/socioeconomic level was
      also a significant incidence predictor. Older age characterized homo/bisexuals.
      The chlamydial infection detection rate was not affected by nationality,
      injecting drug use history or sexual orientation in males. CONCLUSION: Innovative
      preventive and control strategies are needed among immigrants, older men having
      sex with men and injecting drug users, apart from those targeting the general
      population.

PMID- 14636204
TI  - IgG antibody reactivity to Borrelia burgdorferi sensu stricto antigens in
      patients with morphea in Colombia.
AB  - BACKGROUND: Morphea and lichen sclerosus et atrophicus (LSA) are sclerotic skin
      lesions of unknown etiology involving connective tissue. The hypothesis of a
      borrelial origin of morphea and LSA is currently controversial. METHODS:
      Immunoglobulin G (IgG) immunoblot serologies against Borrelia burgdorferi in
      patients with morphea and LSA were analyzed and compared with those from healthy
      donors and patients with syphilis to determine the association with a probable
      borrelial agent in Colombia. RESULTS: No significant differences in the number of
      reactive antigenic bands were found between morphea/LSA patients and syphilis
      patients or healthy donors. The presence of at least one of the following bands,
      p28, p39, or p45, was the criterion most able to distinguish morphea/LSA,
      yielding a specificity of 95% and a sensitivity of 28.6%. Using this criterion as
      evidence of putative exposure to a causative borrelial agent, sclerotic skin
      lesions had an odds ratio of 7.60 (95% confidence interval, 1.47-39.23).
      CONCLUSIONS: These results could be explained by cross-reactivity; however, the
      partial shared reactivity of sera from patients with syphilis and morphea/LSA
      does not rule out the possibility that a new spirochetal agent, unrelated to B.
      burgdorferi or Treponemas, may be the causative agent of morphea/LSA in Colombia.

PMID- 14636205
TI  - Prevalence of skin diseases in rural areas of Assiut Governorate, Upper Egypt.
AB  - BACKGROUND: Few epidemiological surveys have been carried out to determine the
      prevalence of skin diseases in the population of Egypt, particularly "Upper
      Egypt". So it is a pressing necessity to conduct such a study in rural Assiut.
      OBJECTIVES: To determine the prevalence of various skin diseases in rural Assiut.
      SUBJECTS AND METHODS: A cross-sectional community-based survey was followed. The
      survey included 8008 rural inhabitants of all ages and both sexes from a
      representative of three villages of Assiut Governorate, Upper Egypt. The data
      were collected through personal interview and examination at homes from December
      1994 to December 1996. RESULTS: They showed that 6961 (86.93%) of the studied
      population had one or more skin diseases. The group with parasitic skin
      infestations had the highest prevalence rate (27.40%) of the total sample, of
      which pediculosis capitis (19.37%) was the commonest. Eczema/dermatitis group had
      a rate of 19.82%, with pityriasis alba forming the majority (13.49%). Pigmentary
      disorders were 17.68%, followed by fungal skin infections (16.17%), then naevoid
      disorders (16.10%), hair and scalp disorders (12.07%), bacterial skin infections
      (10.10%), sweat gland disorders (6.16%), acne vulgaris (5.37%). Leprosy
      constituted 1.6/10,000. Other various skin disorders were recorded. CONCLUSIONS:
      Infective-parasitic diseases were a major problem particularly among the younger
      age-group and those of low socio-economic status.

PMID- 14636206
TI  - Lepromatous leprosy and reversal reaction in a Micronesian immigrant.
AB  - A 25-year-old Micronesian man from the island of Otia developed erythematous
      plaques on his legs. He was diagnosed with erythema nodosum and treated with
      systemic prednisone. Two months later, he presented with erythematous nodules on
      his forehead, cheeks, and chin (Fig. 1). Examination revealed scattered
      violaceous papules on his chest, arms, forearms, hands, and feet, and deep purple
      macules on his palms and soles. Laboratory evaluation included negative
      serologies for human immunodeficiency virus, rapid plasma reagin, and hepatitis
      A, B, and C. Routine histopathology revealed nodular aggregates of histiocytes,
      plasma cells, and lymphocytes. Histiocytes showed basophilic clusters of
      organisms within vacuoles, suggesting globi. Acid-fast stain revealed numerous
      acid-fast-positive rod-shaped organisms. The bacterial index on the Fite stain
      was four (bacterial index/Ridley's logarithmic scale, indicating 10-100
      bacteria/high power field) (Fig. 2). An acid-fast stain obtained from a smear of
      tissue was positive for acid-fast bacilli, but no acid-fast bacilli were
      cultured. After the first day of treatment with dapsone 100 mg, rifampin 600 mg,
      and clofazimine 50 mg, the patient complained of burning and pain in his ankles
      and wrists. There was intense erythema within the lesions. Edema developed in his
      hands and feet. Consultation with the Gillis W. Long Hansen's Disease Center in
      Carville, Louisiana, recommended prompt treatment with corticosteroids. The edema
      of the hands and wrists was treated as a type I reversal reaction with prednisone
      1 mg/kg/day. Subsequently, the edema and neuralgia quickly resolved in his distal
      extremities.

PMID- 14636207
TI  - Eczematous halo reaction in congenital pigmented nevus.

PMID- 14636208
TI  - Cutaneous Wegener's granulomatosis (malignant pyoderma) in a patient with Crohn's
      disease.
AB  - We report a case of an unusual presentation of Wegener's granulomatosis (WG) in a
      patient with Crohn's disease (CD). She presented to our Wound Care Center with
      7th cranial nerve palsy and facial pyoderma-like ulcerations. Although WG has a
      predilection for the lung, kidney, and eyes, cutaneous involvement can be seen in
      50% of the cases, and it can be the presenting sign in 9-14%. Because of the
      lethality of WG if not properly treated, the diagnosis is imperative.

PMID- 14636209
TI  - Wegener's granulomatosis presenting as pyoderma gangrenosum.
AB  - A 59-year-old male patient developed a necrotizing ulceration on the right shin.
      Both clinical and histopathologic examinations suggested pyoderma gangrenosum.
      After temporary improvement of skin symptoms under peroral glucocorticoid
      treatment, a hemorrhagic-purulent discharge started from the nose, he began to
      have fever, malaise, cough, and a chest X-ray revealed inflammation in the lung.
      Cerebral CT and MRI disclosed midline bone loss within the nasal septum and
      granulomatosus tissue masses protruding into the right orbit. The c-ANCA test was
      positive, serum IgA was elevated, and he had microhaematuria and proteinuria. In
      this severe case of Wegener's granulomatosis prolonged methylprednisone and
      cyclophosphamide treatment was initiated. Both the skin symptoms and the
      granulomatosus infiltrations resolved.

PMID- 14636210
TI  - Limited Wegener's granulomatosis manifesting as malignant pyoderma with corneal
      melt.

PMID- 14636211
TI  - Verrucae vulgares: flashlamp-pumped pulsed dye laser treatment in 134 patients.
AB  - BACKGROUND: Various approaches have been taken in the management of verrucae
      vulgares, but there is still no first-choice treatment. Thus, a study was
      designed to evaluate the efficacy of a flashlamp-pumped pulsed dye laser (FPDL)
      in the treatment of verrucae vulgares. METHODS: Within 18 months, 134 patients
      with recalcitrant or untreated verrucae vulgares on their hands or feet, or in
      other sites, were exposed to a 585-nm FPDL every 3.26 weeks. The following
      parameters were used: energy density, 8 J/cm2; spot size, 7 mm; pulse duration,
      450 micro s. Concomitant topical treatment was not recommended. RESULTS: Eight
      patients were lost to follow-up. The data of 126 patients were evaluated. Up to
      eight laser treatments led to total remission in 62.69% of patients and partial
      remission in 21.42%; 9.52% did not respond to this type of management; 6.34% of
      patients classified the method as too painful and withdrew after the first one or
      two treatments. In a median follow-up period of 5.38 months (2-16 months), one
      relapse occurred. CONCLUSIONS: FPDL is safe and effective for the removal or
      reduction of verrucae vulgares, and requires less patient compliance compared
      with other treatment options.

PMID- 14636212
TI  - Critical review of the manner in which the efficacy of therapies for rosacea are
      evaluated.
AB  - BACKGROUND: Rosacea is a relatively common disorder that may affect individuals
      of all races, particularly those of northern European decent. Its onset generally
      occurs in individuals between the ages of 20 and 50 years. Rosacea may be
      classified into four subtypes and one variant. Although individuals with rosacea
      may not pass through all of the stages, the primary features of the disorder
      include frequent flushing and blushing, nontransient erythema, the presence of
      papules and pustules, and telangiectasia. Many agents have been used to treat
      rosacea stigmata, especially because none of these is uniformly effective. AIM:
      To identify the parameters that are used to evaluate the response to therapy when
      different agents are used to treat rosacea. For a given parameter, to determine
      whether the different trials are consistent in the manner in which this variable
      is measured. METHODS: The reports on the efficacy and safety of the different
      drug therapies used to treat rosacea were identified. We searched MEDLINE (1966
      to June 2002) for studies where rosacea was treated. The parameters used to
      evaluate the efficacy of therapy were determined. For each parameter, the ways in
      which it has been measured were identified. RESULTS: Efficacy of treatment is
      generally judged by evaluating the effect of the intervention on papules and
      pustules, erythema, and telangiectasia. Manual lesional counts of papules and
      pustules are usually performed. There is, however, substantial variation in the
      methodology chosen for comparison of erythema and telangiectasias. Color scales
      are popular for erythema and telangiectasia, while grading scales are most
      commonly used for physician and patient evaluations. CONCLUSIONS: For each of the
      parameters that are commonly used to measure the efficacy of treatments for
      rosacea, the different approaches by which it has been measured in the various
      trials have been highlighted; these dissimilarities can make it problematic to
      compare between clinical trials. A greater degree of uniformity in the manner in
      which the various parameters are evaluated would enable a more objective
      comparison between the studies.

PMID- 14636213
TI  - Swimmer's itch: An assessment proposing possible treatment with ivermectin.

PMID- 14636214
TI  - Topical tretinoin in Indian male with zosteriform porokeratosis.

PMID- 14636216
TI  - Simultaneous increase in germ cell apoptosis and oxidative stress under acute
      unilateral testicular ischaemia in rats.
AB  - Ischaemia induced germ cell apoptosis in rat testis was studied in detail to find
      out (i) spermatogenic stage or seminiferous epithelium region specific
      involvement of germ cells in apoptosis, (ii) preferential specificity of a
      particular germ cell type to become apoptotic and (iii) the ratio of live and
      dead testicular cells isolated in vitro after various period of ischaemic
      induction. Cell apoptosis, as observed in histological sections increased from 1
      to 24 h of ischaemia. Apoptosis was not restricted to any specific germ cell type
      but was observed simultaneously in all the cell types in the initial hours (1-6
      h) of ischaemia. No spermatogenic stage specific preference in apoptotic
      induction was also observed. However, as the duration of ischaemia progressed,
      the cell types observed to be most affected in number and morphology were the
      spermatids followed by spermatocytes. Centrally located tubules of testis were
      affected first than those located in the periphery. Overexpression of Bax
      staining was limited to few germ cell nuclei only. More than 95% of the germ
      cells in the control testis that earlier showed trypan blue dye exclusion were
      found stained after 12 h of ischaemia. Starting from early hours (1 h), lipid
      peroxidation rose proportionally with the duration of ischaemia while superoxide
      dismutase (SOD) and catalase activities were found decreased. Significant (p <
      0.05) increase in the activities of glutathion-s-transferase and levels of
      hydrogen peroxide were observed after 6 h of ischaemia. These findings indicate
      that the physiological processes of oxidative stress have a direct linkage to the
      extent of germ cell apoptosis in the seminiferous epithelium.

PMID- 14636217
TI  - Premature ejaculation in non-insulin-dependent diabetic patients.
AB  - Aim of the study was to assess the prevalence and to analyse risk factors for
      premature ejaculation (PE) in patients with non-insulin-dependent diabetes. A
      total of 676 male diabetic patients were enrolled in this study. Patients were
      screened for PE. At the screening time, patients were also interviewed for
      sociodemographic data that included age, education, occupation and marital
      status. Medical history included diabetes, duration of diabetes and diabetes
      related complications. Clinical and laboratory assessment included body mass
      index and glycosylated haemoglobin. Mean age for the study sample was 53.4 +/-
      10.4 years. The prevalence of PE was 32.4% in patients below 50 years, which
      increased to 67.6% in patients above 50 years. Of patients without PE, 31.4% were
      below 50 years compared with 68.6% above 50 years of age (p > 0.05). Patients
      with >10 years of diabetes were 2.7 times as likely to report PE as men with
      diabetes of <5 years (p < 0.05). Men with poor metabolic control were 9.6 times
      as likely to report PE as those with good metabolic control (p < 0.05). Patients
      without PE were four times as likely to have normal erectile function as those
      with PE (p < 0.05). There was a significant association between PE and
      cardiovascular diseases (p < 0.05). PE is common among diabetic patients. The
      study offers a quantitative estimate of the prevalence of PE and its main risk
      factors in diabetic patients.

PMID- 14636218
TI  - Leptin and leptin receptor in human seminal plasma and in human spermatozoa.
AB  - Leptin, a 167 amino acid peptide, is known to influence the gonads via direct and
      indirect effects. Recent studies provide contradictory proposition about the
      peripheral impact of leptin in the male gonads. Thus, we examined leptin and its
      receptors in human seminal plasma and in human ejaculated spermatozoa by Western
      blot technique and fluorescence microscopy. In seminal plasma we found a free
      leptin band (16 kDa) by an anti-leptin polyclonal antibody. Incubation of seminal
      plasma with recombinant leptin caused a statistically significant increase in the
      amount of free leptin (p < 0.01) and supports this finding. Furthermore, a
      soluble leptin receptor (145 kDa) was found in human seminal plasma in the same
      specimen. We also detected a 145-kDa leptin receptor isoform in ejaculated
      spermatozoa as a possible target of leptin action in the male genital tract,
      which was localized at the tail of spermatozoa by immunofluorescence microscopy
      only. This receptor was significantly associated with the intactness of sperm
      plasma membranes. Spermatozoa with deteriorated membranes contained 49.2 +/- 6.9%
      leptin receptor signal intensity compared with spermatozoa having intact
      membranes (p < 0.01). This finding is difficult to interpret and may be caused by
      a leakage of OB-R due to loss of membrane integrity. In conclusion, these data
      provide further hints for a peripheral role of leptin in the male genital tract,
      possibly, by an interaction between leptin and spermatozoa via sperm leptin
      receptors.

PMID- 14636219
TI  - Evaluation of the effect of 17alphaOH-progesterone and 17beta-oestradiol on human
      sperm ability to fuse with oocytes: comparison and possible interference with the
      effect of progesterone.
AB  - The demonstration of a stimulatory effect of progesterone (P) on the sperm/oocyte
      fusion has provided the most relevant biological evidence of the effect of P on
      sperm functions involved in fertilization. Some evidence exists that 17alpha
      hydroxyprogesterone (17alphaOH-P) and 17beta-oestradiol (17beta-E2), could also
      exert non-genomic effects on human spermatozoa and a role for 17beta-E2 as a
      possible physiological modulator of P action on spermatozoa has been suggested.
      This study aimed to determine the effect of the exposure of human spermatozoa to
      17alphaOH-P and 17beta-E2 on sperm/oocyte fusion as well as the possible
      interference of 17beta-E2 with the effect of P. The effect of steroids on
      sperm/oocyte fusion was assessed by means of the hamster egg penetration test
      (HEPT). The exposure of capacitated sperm suspensions to scalar doses of
      17alphaOH-P produced a significant enhancement of penetrations/oocytes with a
      dose/response effect. It was equal to 75.3% of that produced by equimolar doses
      of P. Conversely, 17beta-E2 (from 100 nM to 50 microM) did not produce any
      significant effect when added either before or after capacitation. Moreover, the
      sperm pre-incubation with 17beta-E2 did not interfere with the stimulatory effect
      of P. These results support a physiological role for 17OH-P in the process of
      fertilization, but not a role for 17beta-E2 as a possible physiological modulator
      of P action on spermatozoa.

PMID- 14636220
TI  - Intercellular bridges and apoptosis in clones of male germ cells.
AB  - When an As spermatogonium divides to form a pair of Apr spermatogonia the two
      daughter cells stay interconnected by an intercellular bridge. These cytoplasmic
      bridges form after every subsequent division leading to large clones of
      interconnected germ cells. Cohorts of spermatogonia maintain synchronous
      development throughout spermatogenesis, which has been attributed to the presence
      of these intercellular bridges. To examine whether apoptotic signals are
      transduced through the intercellular bridges we studied germ cell apoptosis in
      whole mounts of seminiferous tubules from non-irradiated and irradiated mouse
      testes, using whole mount seminiferous tubules and confocal microscopy. This
      allowed us to use TUNEL staining of apoptotic germ cells and at the same time to
      study these apoptotic germ cells in their topographical context. Our results show
      that in response to ionizing radiation single spermatogonia within a clone can
      undergo apoptosis without affecting their neighboring cells. Additionally, also
      early spermatocytes were shown to undergo apoptosis individually. Both radiation
      induced spermatogonial apoptosis and spontaneous apoptosis of spermatocytes are
      caused by DNA damage of individual cells. Degeneration of healthy spermatogonia
      because of regulatory signals, however, follows other death inducing mechanisms,
      which lead to apoptosis of chains of interconnected spermatogonia.

PMID- 14636221
TI  - Isolation and characterization of a novel cDNA encoding a DNA-binding protein
      (Hils1) specifically expressed in testicular haploid germ cells.
AB  - A cDNA encoding a protein homologous with histone H1 has been cloned from a
      haploid germ cell specific cDNA library. Deduced amino acid sequence (170 amino
      acids) showed 40% identity with histone H1 globular domain. Messenger RNA of the
      gene was observed exclusively in the testis, and was accumulated after post-natal
      day 23. Western blotting analysis showed that the protein encoded by this gene is
      about 19 kDa in molecular weight, and it was exclusively recovered from the
      nuclei of testicular germ cells. Immunohistochemical analysis showed that the
      protein was localized to the nuclei of round and elongating spermatids,
      consistent with the results of immunoblot analysis. Thus, the gene product was
      named Hils1 (histone H1 like protein in spermatids 1). In vitro DNA-binding
      experiments using DNA-cellulose mini-columns showed that Hils1 was able to bind
      to both double and single stranded-DNAs in a non-sequence-specific manner. These
      findings suggest that Hils1 may play an important role in the structural changes
      of spermatid nuclei, such as nuclear condensation, and gene regulation of haploid
      germ cell differentiation.

PMID- 14636222
TI  - Effects of Ca-ATPase inhibitors on the intracellular calcium activity and
      motility of human spermatozoa.
AB  - Although evidence suggests that high intracellular calcium activity ([Ca2+]i)
      inhibits sperm motility, data concerning [Ca2+]i within, or slightly above, the
      physiological range are sparse, particularly in mammalian sperm. We investigated
      inhibitors of the sarcoplasmic/endoplasmic reticulum Ca-ATPase (SERCA) and the
      plasma membrane Ca-ATPase with the objective of increasing the intracellular
      calcium ion activity in human spermatozoa to study its effect on motility and
      other functions. Thapsigargin (20 micromol/L) increased [Ca2+]i from 140 +/- 7
      nmol/L over an approximately 2-min period to reach a plateau of 530 +/- 84 nmol/L
      (mean +/- SEM, n = 3, p < 0.05). In sperm suspended in calcium-free medium
      thapsigargin increased [Ca2+]i from 13 +/- 3.3 to 35 +/- 7.5 nmol/L (p < 0.01),
      consistent with the release of calcium from intracellular stores. Cyclopiazonic
      acid (60 micromol/L) caused a transient decrease in [Ca2+]i. Quercetin, (200
      micromol/L) caused a rapid increase in [Ca2+]i to 1280 +/- 90 nmol/L, after which
      [Ca2+]i fell quickly at first but then more slowly. Thapsigargin (20 micromol/L)
      caused approximately 70% of sperm to acrosome react in < or = 5 min, but once
      acrosome reacted, many sperm died over the next 30 min. Lower concentrations of
      thapsigargin caused fewer acrosome reactions but were less toxic. Both
      thapsigargin and quercetin caused rapid dose-dependent decreases in sperm
      motility. The results are consistent with high [Ca2+]i in the range observed in
      caput epididymal or cryopreserved spermatozoa inhibiting motility, but might be
      confounded by other events following the acrosome reaction.

PMID- 14636224
TI  - Congratulations and other observations.

PMID- 14636226
TI  - Indoor air quality and energy performance of air-conditioned office buildings in
      Singapore.
AB  - An integrated indoor air quality (IAQ)-energy audit methodology has been
      developed in this study in Singapore, which provides a rigorous and systematic
      method of obtaining the status-quo assessment of an 'IAQ signature' in a
      building. The methodology entails a multi-disciplinary model in obtaining
      measured data pertaining to different dimensions within the built environment
      such as the physical, chemical, biological, ventilation, and occupant response
      characteristics. This paper describes the audit methodology and presents the
      findings from five air-conditioned office buildings in Singapore. The research
      has also led to the development of an indoor pollutant standard index (IPSI),
      which is discussed in this paper. Other performance indicators such as, the
      ventilation index and the energy index as well as the building symptom index
      (BSI) are also presented and discussed in the context of an integrated approach
      to IAQ and energy. Several correlation attempts were made on the various
      symptoms, indoor air acceptability, thermal comfort, BSI and IPSI, and while BSI
      values are found to correlate among them as well as with IAQ and THERMAL COMFORT
      acceptability, no such correlation was observed between BSI and IPSI. This would
      suggest that the occupants' perception of symptoms experienced as well as
      environmental acceptability is quite distinct from IAQ acceptability determined
      from empirical measurements of indoor pollutants, which reinforces the complex
      nature of IAQ issues.

PMID- 14636227
TI  - The link between symptoms of office building occupants and in-office air
      pollution: the Indoor Air Pollution Index.
AB  - The lack of an effective indoor air quality (IAQ) metric causes communication
      concerns among building tenants (the public), building managers (decision
      makers), and IAQ investigators (engineers). The Indoor Air Pollution Index (IAPI)
      is developed for office buildings to bridge this communication discord. The
      index, simple and easily understood, employs the range of pollutant
      concentrations and concentrations in the subject building to estimate a unitless
      single number, the IAPI, between 0 (lowest pollution level and best IAQ) and ten
      (highest pollution level and worst IAQ). The index provides a relative measure of
      indoor air pollution for office buildings and ranks office indoor air pollution
      relative to the index distribution of the US office building population.
      Furthermore, the index associates well with occupant symptoms, percentage of
      occupants with persistent symptoms. A tree-structured method is utilized in
      conjunction with the arithmetic mean as the aggregation function. The
      hierarchical structure of the method renders not only one index value, but also
      several sub-index values that are critical in the study of an office air
      environment. The use of the IAPI for IAQ management is illustrated with an
      example. The decomposition of the index leads to the ranking of sampled
      pollutants by their relative contribution to the index and the identification of
      dominant pollutant(s). This information can be applied to design an effective
      strategy for reducing in-office air pollution.

PMID- 14636228
TI  - Significance of humidity and temperature on skin and upper airway symptoms.
AB  - The objective of the present study was to assess the effect of absolute and
      relative humidity, temperature and humidification on workers' skin and upper
      airway symptoms, and perceptions in the office environment. Associations between
      physical factors, and symptoms and perceptions were assessed in logistic
      regression models. At temperatures between 18 and 26 degrees C, relative humidity
      of 17-40%, and absolute humidity of 3.3-5.6 g H2O/kg air, skin symptoms and nasal
      dryness and congestion were alleviated by both kinds of humidity. Pharyngeal
      dryness increased when temperatures rose and was alleviated with a rise in
      relative humidity. Eye symptoms showed no dependence on humidity. Any kind of
      humidity increased odor sensation. Stuffiness increased when the air was
      humidified. In non-humidified conditions (21.3-22.7 degrees C, 20.0-31.7%, 3.3
      5.6 g H2O/kg air), skin and nasal symptoms showed no association with humidity or
      temperature. Pharyngeal dryness diminished when humidity rose. In addition, the
      association between humidity and odor disappeared. In humidified conditions (21.5
      23.7 degrees C, 26.6-41.2%, 4.2-7.0 g H2O/kg air), nasal dryness and congestion
      were alleviated by both absolute and relative humidity, and odor perception
      increased. Skin dryness and rash, pharyngeal dryness, and nasal dryness and
      congestion are alleviated in higher humidity. Steam humidification results in a
      risk for increased perception of odor and stuffiness.

PMID- 14636229
TI  - Variability of airborne cat allergen, Fel d1, in a public place.
AB  - Allergen exposure is a risk to develop an IgE-mediated sensitization. The amount
      of allergen inhaled per unit time should be related to the amount present in the
      air, i.e. airborne allergen. Thus, measuring allergen levels in the air would be
      more relevant than measuring allergen levels in dust. Allergens are present in
      the air in very minute quantities and usually become airborne after disturbance.
      Large variation of allergen levels have been found in dust. In this study, we
      measured variability of airborne cat allergen, Fel d1, in a public place using a
      high-volume air-sampler. We also studied the distribution and relationship
      between dust and airborne cat allergens in homes and schools. Air samples were
      collected at three different airflow rates, i.e. 55, 40, and 30 m3 of air per
      hour. The concentration of airborne Fel d1 in the community gymnastic hall varied
      from 1 to 10 pg/m3 within a period of 3 weeks, at airflow rates 55-30 m3/h. The
      coefficient of variation for repeated samplings was 14-43% (day-to-day variation)
      and 27-38% (within-day variation). As expected, higher levels of airborne cat
      allergens were found in homes with cats than in cat-free environments. There was
      a significant relationship between cat allergen levels in dust and air (r=0.7,
      P<0.01). Our study demonstrates that when measuring airborne cat allergen a large
      variation is observed within a day and between days. The large variability of
      measurement may be explained by the disturbance in the environments. We suggest,
      that when exposure assessment is made the environment in question should be
      analyzed, if possible in several occasions.

PMID- 14636230
TI  - Risk assessment of formaldehyde in typical office buildings in Taiwan.
AB  - Our study conducts a series of investigations in five office buildings chosen
      according to the types of construction, ventilation, and building age.
      Formaldehyde was measured by continuous photoacoustic Multi-Gas monitor Type 1302
      (Bruel & Kjaer). The 8-h average concentrations in working hours were used to
      estimate the lifetime cancer probability (LCP) and chronic non-carcinogenic
      hazard index (HI). The carcinogenic effect of formaldehyde estimate by LCP (70
      years old) is about 2.06 x 10(-4) to 1.75 x 10(-3) after adjusting their working
      time. The levels of risk are 100-1000 times of the acceptable carcinogenic risk.
      A similar trend is observed for the levels of HI calculated. Many studies have
      suggested that exposure to high levels of formaldehyde may cause nasal cancer and
      other health effects. Therefore, promoting the labeling system for low emission
      materials to protect consumers from exposure to excessive emissions and helping
      the industry to develop low emission materials is evidently urgent and deserves
      greater efforts.

PMID- 14636231
TI  - Indices for IEQ and building-related symptoms.

PMID- 14636232
TI  - Biomarkers and other substitute measures in indoor air sciences.

PMID- 14636233
TI  - Are we ready for indoor air pollution indices?

PMID- 14636238
TI  - Depletion of cellular cholesterol interferes with intracellular trafficking of
      liposome-encapsulated ovalbumin.
AB  - Cholesterol is a major constituent of plasma cell membranes and influences the
      functions of proteins residing in the membrane. To assess the role of cholesterol
      in phagocytosis and intracellular trafficking of liposomal antigen, macrophages
      were treated with inhibitors of cholesterol biosynthesis for various time periods
      and levels of cholesterol depletion were assessed by thin layer chromatography.
      In control macrophages, cholesterol was present in the plasma membrane and in
      intracellular stores, as visualised by staining with the cholesterol-binding
      compound filipin, whereas macrophages treated with cholesterol inhibitors failed
      to stain with filipin. However, these macrophages were still capable of
      phagocytosis as evidenced by their internalisation of fluorescent-labelled
      bacteria and liposome-encapsulated Texas red labelled-ovalbumin, L(TR-OVA). While
      fluorescent ovalbumin (OVA) was consistently transported to the Golgi in
      macrophages incubated with L(TR-OVA), in cells treated with cholesterol
      inhibitors, OVA remained spread diffusely throughout the cytoplasm. Even though
      the mean fluorescence intensity of MHC class I molecules on cholesterol inhibitor
      treated macrophages was equivalent to that of the control macrophages, the amount
      of MHC class I-liposomal OVA-peptide complex detected on the cell surface of
      cholesterol inhibitor-treated macrophages, was only 45.6 +/- 7.4% (n = 4, mean +/
      SEM) of control levels after intracellular processing of L(OVA). We conclude
      that cholesterol depletion does not eliminate phagocytosis or MHC class I surface
      expression, but does affect the trafficking and consequently the MHC class I
      antigen-processing pathway.

PMID- 14636239
TI  - IL-4 from Th2-type cells suppresses induction of delayed-type hypersensitivity
      elicited shortly after immunization.
AB  - The pure delayed-type hypersensitivity reaction obtained in 4-day ovalbumin
      sensitized mice after antigen challenge in the footpad was abrogated by transfer
      of in vitro expanded, antigen-specific lymphoblasts derived from ovalbumin
      hyperimmunized donors (high antibody producers), 12 h before immunization. This
      effect was specific inasmuch as Trypanosoma cruzi-specific blasts derived from Tc
      Ag-hyperimmunized mice did not inhibit delayed-type hypersensitivity in ovalbumin
      immunized recipients. The ovalbumin-specific blasts displayed a Th2 cytokine
      profile, secreting IL-4 and IL-10 upon restimulation in vitro with ovalbumin, but
      not IFN-gamma or IL-2. In addition, recipients of such cells produced much more
      IgG1 and IgE antibodies. When the frequency of T-cell blasts was enriched among
      these cells, transfer of four million cells was enough to prevent the induction
      of delayed-type hypersensitivity. Neutralization of IL-4 alone just before cell
      transfer not only restored the delayed-type hyper-sensitivity reaction, but also
      maintained it in a plateau for at least 72 h after challenge. Recipients treated
      in this way also showed a shift back towards a Th1 phenotype, indicated by the
      increase in IL-2, IFN-gamma and IL-12 synthesis. No synergistic action was
      observed when IL-4 and IL-10 were concomitantly neutralized. These results
      indicate that activation of Ag-specific Th2 cells early in the course of the
      immune response to a protein antigen provides an immunological environment rich
      in IL-4, thus leading to the inhibition of cell-mediated immunity.

PMID- 14636240
TI  - Listeria species escape from the phagosomes of interleukin-4-deactivated human
      macrophages independent of listeriolysin.
AB  - Listeria monocytogenes is the causative agent of infections like sepsis and
      meningitis, especially in immunocompromised hosts. Human macrophages are able to
      phagocytose and digest L. monocytogenes but IL-4 prevents human macrophages from
      killing the bacteria, the mechanisms of which are unknown. In the present study,
      we examined various listeria species and strains including wild-type and deletion
      mutants in human macrophages pretreated with IL-4. To analyse the IL-4-mediated
      deactivation process, we combined quantitative infection assays with various
      morphologic methods. IL-4 facilitates survival and escape of the pathogenic L.
      monocytogenes wild-type strain 10403S from the macrophage phagosomes. In
      untreated macrophages, the isogenic listeriolysin deletion mutant strain DP-L2161
      was killed and did not escape from the phagolysosomes. However, after macrophage
      deactivation with IL-4 DP-L2161 survived and escaped from the phagosomes. This
      was also the case, but to a lesser extent, even for the naturally avirulent L.
      innocua. As detected by confocal laser-scanning fluorescence microscopy and
      electron microscopy, IL-4 permitted the escape of all listeria species tested,
      including DP-L2161 and L. innocua from the phagosomal compartment of the
      macrophages. We conclude that escape from the phagosome and survival of the
      listeria species tested in IL-4-deactivated human macrophages is independent of
      the virulence factor listeriolysin.

PMID- 14636241
TI  - Fibroblast growth factor receptor-1 interacts with the T-cell receptor signalling
      pathway.
AB  - Fibroblast growth factor receptors are expressed by some T cells, and provide
      costimulation for these cells. Such receptors allow T cells to respond to
      fibroblast growth factors expressed in response to injury and inflammation and
      may provide a mechanism for 'context-dependent' responses to antigens within the
      local microenvironment. The mechanisms by which fibroblast growth factor
      receptors might interact with the TCR signalling pathway are not defined. Here we
      show that the TCR and fibroblast growth factor receptors co-localize during
      combined stimulation. Signalling via fibroblast growth factor receptors alone
      results in phosphorylation of Lck and induces nuclear translocation of nuclear
      factors of activated T cells. Combined stimulation via fibroblast growth factor
      receptors and the TCR synergistically enhances the activation of nuclear factors
      of activated T cells. The results suggest that peptide growth factors produced at
      sites of injury and inflammation can contribute to the outcome of T-cell
      encounters with antigen.

PMID- 14636242
TI  - Activated macrophages require T cells for xenograft rejection under the kidney
      capsule.
AB  - Transplantation of tissues from other species has been advocated as a way to
      overcome the extreme shortage of human donors. Rejection, however, remains a
      major hurdle for clinical xenotransplantation. Although activation of macrophages
      by T cells is critical for the cellular rejection of xenografts, what other
      important interactions between these two types of cells remain less defined. When
      we activated macrophages of immuno-deficient mice (SCID or Rag-/-) using
      interferon-gamma and lipopolysacharide, xenogeneic cells were rejected by
      activated macrophages in the peritoneal cavity (which has an abundance of
      resident macrophages), but were not rejected under the kidney capsule (which
      requires the recruitment of effectors). This difference between the two sites
      implies that activated macrophages are inefficient for self-recruitment to
      peripheral graft sites and that T cells may still be required for the process. To
      test this hypothesis further, immunodeficient mice that had received xenogeneic
      cells were infused with peritoneal exudate cells (containing activated
      macrophages and activated T cells) from preimmunized immunocompetent mice.
      Xenogeneic cells at both the kidney capsule and peritoneal sites were rejected
      soon after cell transfer. However, when the exudate cells were transferred into
      SCID recipients that first had been injected with T cell depleting antibodies,
      xenograft rejection was only prominent at the peritoneal site but not kidney
      capsule site. These results argue that activated macrophages (as the result of T
      cell activation) still require T cells for xenograft rejection at peripheral
      sites.

PMID- 14636243
TI  - Enhancing CTL responses to melanoma cell vaccines in vivo: synergistic increases
      obtained using IFNgamma primed and IFNbeta treated B7-1+ B16-F10 melanoma cells.
AB  - Sequentially treating human melanoma cell lines by priming with interferon-gamma
      before adding interferon-beta was previously found to be the most efficient
      protocol for producing concurrently increased expression of the three surface
      antigens B7-1, intercellular adhesion molecule-1 and human histocompatibility
      leucocyte antigens Class I. The present study describes similar outcomes when the
      same sequential intercellular adhesion molecule-based protocol is applied to
      murine B16-F10 melanoma cells as well as preclinical studies using the B16-F10
      model as a poorly immunogenic melanoma. Thus, treating B16-F10 cells or a highly
      expressing B7-1 transfected subline (B16-F10/B7-1 hi) by priming with interferon
      gamma for 24 h before adding interferon-beta for a further 48 h (interferon-gamma
      72/beta 48) increased expression of all three surface antigens, particularly
      major histocompatibility complex class I whose increased expression was sustained
      for several days. As a whole tumour cell vaccine, interferon-gamma 72/beta 48
      treated B16-F10 cells produced greater levels of cytoxic T lymphocyte response
      compared to vaccines prepared from cells treated with a single type of
      interferon. Furthermore, B16-F10 cells expressing high levels of B7-1 and treated
      using the interferon-gamma 72/beta 48 protocol (interferon-gamma 72/beta 48
      treated B16-F10/B7-1 hi) produced substantially increased cytoxic T lymphocyte
      responses with a fivefold greater synergy than the combined results of either
      interferon treated or B7-1 expressing cells tested individually. The resulting
      CD8+ cytoxic T lymphocyte showed greater specificity for B16-F10 cells with
      tenfold higher killing than for syngeneic EL-4 lymphoma cells. Killing proceeded
      via the perforin-mediated pathway. CTL responses were induced independent of CD4+
      T helper cells. The majority of mice receiving interferon-gamma 72/beta 48
      treated B16-F10/B7-1 hi vaccine in vivo remained tumour free after challenge with
      5 x 105 live B16-F10 cells expressing intermediate B7-1 levels. The novel
      strategy described will help enhance vaccine potency when applied clinically to
      prepare whole cell based cancer vaccine therapies.

PMID- 14636244
TI  - The inducibility of TNF-alpha production is different in the granulocytic and
      monocytic differentiated forms of wild type and CGD-mutant PLB-985 cells.
AB  - Chronic granulomatous disease is an inherited disorder associated with a defect
      in phagocytic cell oxidative metabolism resulting in ineffective microbicidal
      activity. Consequently, patients with chronic granulomatous disease suffer from
      recurrent infections. Published data show that besides the failure to produce
      superoxide and its derivatives, other functional problems can also be found in
      chronic granulomatous disease-mutant cells. Since in innate immune responses
      other mediators, such as cytokines, also play an important role, we hypothesized
      that there may be a disturbance in cytokine production by chronic granulomatous
      disease-mutant cells as well. To prove this hypothesis, the production of tumour
      necrosis factor-alpha, an important proinflammatory cytokine, was determined by
      enzyme-linked immunosorbent assay in wild-type and chronic granulomatous disease
      mutant myelomonoblastic PLB-985 cells in their immature, granulocytic and
      monocytic/macrophage differentiated forms. Tumour necrosis factor-alpha
      production was induced with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (100
      nmol/L), lipopolysaccharide (10 micro g/mL), opsonized zymosan (100 micro g/mL)
      or phorbol 12-myristate 13-acetate (100 nmol/L) for 24 h. We could demonstrate
      that: (i) there were marked differences in tumour necrosis factor-alpha
      production only in the differentiated forms of both wild-type and chronic
      granulomatous disease-mutant cells, while there were no differences in the case
      of their immature counterparts; (ii) only chronic granulomatous disease-mutant
      cells retained sensitivity to phorbol 12-myristate 13-acetate both in their
      granulocytic and monocytic forms, although phorbol 12-myristate 13-acetate
      responsiveness was a characteristic of both types of immature cells; (iii) the
      granulocytic form of wild-type cells produced tumour necrosis factor-alpha after
      opsonized zymosan stimulation, but such a response was not observed in cells
      originating from the chronic granulomatous disease-mutant cell line; (iv) with
      the monocytic forms, significantly higher tumour necrosis factor-alpha production
      could be induced by lipopolysaccharide in the wild-type cells than in the chronic
      granulomatous disease-mutant cells, although there was no difference in their
      lipopolysaccharide receptor CD14 expression. In summary, these data show an
      altered inducibility of tumour necrosis factor-alpha production by chronic
      granulomatous disease-mutant cells. Our observations suggest a further defect in
      differentiated chronic granulomatous disease-mutant cells in addition to the
      known defect in reduced nicotinamide adenine dinucleotide phosphate oxidase,
      which may contribute to the development of susceptibility to infections in people
      with chronic granulomatous disease.

PMID- 14636245
TI  - Apoptosis of CD4+ and CD8+ T cells during experimental infection with
      Mycobacterium avium is controlled by Fas/FasL and Bcl-2-sensitive pathways,
      respectively.
AB  - Both CD4+ and CD8+ T cells from mice infected with Mycobacterium avium suffered a
      high rate of apoptosis, beginning with the onset of the immune response and
      culminating in the loss of T cells from the tissues and loss of IFN-gamma
      production. Fas expression increased over the course of infection on both T cell
      populations, as did their susceptibility to the induction of apoptosis in vitro
      by anti-Fas mAb. Nevertheless, although the rate of apoptosis among CD4+ T cells
      from infected mice was reduced to normal levels in lpr mice with a defective Fas,
      CD8+ T cells were unaffected, implying that Fas/FasL interaction was not
      important in these cells in vivo. Conversely, over-expression of B-cell lymphoma
      2 (Bcl-2), which is known to protect T cells from apoptosis signalled through the
      TNF receptor or due to the withdrawal of cytokines, totally protected CD8+ T
      cells from infected mice but had no effect on CD4+. It is of interest that these
      two contrasting pathways of T-cell apoptosis operate at the same time during a
      single infection.

PMID- 14636246
TI  - Naive T cells are maintained by thymic output in early ages but by proliferation
      without phenotypic change after age twenty.
AB  - Analysing T-cell receptor excision circle numbers in healthy individuals we find
      a marked change in the source of naive T cells before and after 20 years of age.
      The bulk of the naive T cell pool is sustained primarily from thymic output for
      individuals younger than 20 years of age whereas proliferation within the naive
      phenotype is dominant for older individuals. Over 90% of phenotypically naive T
      cells in middle age are not of direct thymic origin. Moreover, this change in
      source of naive T cells is accompanied either by an increased death rate of T
      cells from the thymus or reduced thymic export. Modelling of these processes
      shows that new naive T cells of a thymic origin have a half-life of approximately
      50 days before this change occurs, and that either the life-span of recent thymic
      emigrants (but not necessarily of all naive cells) decreases approximately
      threefold in middle age, or thymic production drops by this same amount. The
      decay rate of T-cell receptor excision circle levels for individuals over 20
      years of age is consistent with the decay rate of the productive thymus. Our
      modelling suggests that at age 25, thymic export is responsible for 20% of naive
      T-cell production and that this percentage decreases with the 15.7 year half-life
      of the productive thymus so that by age 55 only 5% of naive production arises
      from thymic export.

PMID- 14636252
TI  - Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical
      relevance.
AB  - Diffuse large B-cell lymphoma (DLBCL), the single largest category of lymphoma,
      is a clinically and biologically heterogeneous disease entity. Clinically,
      patients differ in their mode of presentation and respond variably to therapy. A
      combination of clinical parameters can be used to predict the patient's response
      to therapy and survival. The pathological variability of DLBCL is expressed in
      morphology, immunophenotype, cytogenetic and molecular genetic features. Numerous
      markers detectable by immunohistochemistry and linked to different aspects of
      tumour biology have been studied in DLBCL, including lineage-associated and
      immune markers, proliferation and apoptosis markers, cell adhesion molecules, and
      more recently stage-specific markers of B-cell differentiation. This review
      summarizes these studies in regard to their clinical significance and in the
      light of recent advances in our understanding of the molecular pathology and
      histogenesis of DLBCL.

PMID- 14636253
TI  - Deep penetrating naevus: clinicopathological study of 31 cases with further
      delineation of histological features allowing distinction from other pigmented
      benign melanocytic lesions and melanoma.
AB  - AIMS: To examine a series of deep penetrating naevus (DPN) and discuss the
      differential diagnosis of pigmented, deep penetrating melanocytic lesions and
      their biological potential. DPN has been described as a variant of common
      acquired intradermal melanocytic naevus. DPN remains poorly recognized by
      pathologists, partly attributable to its relatively rare occurrence. METHODS AND
      RESULTS: Thirty-one cases of deeply pigmented lesions were studied. The patients
      included 17 females and 14 males with an age range between 3 and 56 years (mean
      25.8, median 23). The common clinical sites were face (n = 10) back (n = 6) and
      lower extremity (n = 7). The clinical diagnoses included various benign
      melanocytic naevi, and malignant melanoma, as well as non-melanocytic lesions.
      Histologically, all cases presented as wedge-shaped lesions composed of fusiform
      cells but also epithelioid melanocytes, with pale cytoplasm and oval nuclei.
      Pigment was identified in melanophages but also within lesional melanocytic
      cells. Nine cases contained mitotic figures. Nine cases showed the coexistence of
      'ordinary' common acquired naevocytes, and seven lesions showed overlapping
      features with either ordinary blue naevus or Spitz naevus. In 13 lesions there
      was at least one feature that may cause concern as to the biological nature of
      the tumour. These include asymmetry, cytological atypia, inflammation, or an
      'expansile' advancing margin. Each tumour was treated by simple excision; one
      lesion recurred after 1 year. No tumour metastasized. CONCLUSIONS: DPN is a
      distinct variant of melanocytic naevus. In some cases the histological features
      overlap with other benign melanocytic lesions. Criteria for recognizing malignant
      examples remain unclear, but cytological atypia and low mitotic activity do not
      necessarily portend a sinister outcome.

PMID- 14636254
TI  - Mast cell chymase expression in Helicobacter pylori-associated gastritis.
AB  - AIMS: To study the role of mast cell chymase in the inflammatory processes of
      human chronic gastritis. Experimental studies have shown that mast cell chymase
      stimulates inflammatory cell accumulation, and contributes to angiotensin II
      formation. METHODS AND RESULTS: Tissue sections from human stomachs with
      Helicobacter pylori-associated gastritis (surgery/autopsy n = 20; biopsy n = 16)
      and normal stomachs (n = 10) were studied using immunohistochemical single and
      double labelling techniques. Monoclonal antibodies used were directed against
      mast cell chymase, tryptase, neutrophils (CD66b, elastase, and myeloperoxidase),
      macrophages, T-lymphocytes, and interleukin (IL)-4. The expression of angiotensin
      converting enzyme and angiotensin II type 1 receptor was investigated using
      immunohistochemical analysis and the reverse transcription-polymerase chain
      reaction. The number of chymase-positive mast cells was significantly higher (P <
      0.0001) in H. pylori-associated gastritis than in normal stomachs. Increased
      expression of chymase in inflamed mucosa was closely related to an increase in
      the accumulation of neutrophils, macrophages, T-lymphocytes, and IL-4-positive
      cells. The expression of angiotensin-converting enzyme and angiotensin II type 1
      receptor was not altered in gastritis specimens. CONCLUSIONS: These observations
      suggest that mast cell chymase may be an important mediator in the inflammatory
      processes of human H. pylori-associated gastritis.

PMID- 14636255
TI  - Clinicopathological significance of hypoxia-inducible factor-1alpha expression in
      human pancreatic carcinoma.
AB  - AIMS: The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) plays
      a key role in the cellular adaptation to hypoxia and the activation of several
      genes that have been implicated in tumour growth. The aim of this study was to
      investigate the clinicopathological significance of HIF-1alpha expression in
      pancreatic carcinoma. METHODS AND RESULTS: We investigated HIF-1alpha expression
      immunohistochemically in pancreatic carcinoma tissues and regional lymph node
      metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF
      1alpha expression and various clinicopathological parameters including cellular
      proliferation, apoptosis, and microvessel density, was also examined. Over
      expression of HIF-1alpha was frequently (29 of 49 cases, 59.2%) detected in
      pancreatic carcinoma and regional lymph node metastasis (19 of 25 cases, 76.0%),
      whereas HIF-1alpha expression was almost absent in non-cancerous pancreatic
      tissues. HIF-1alpha expression was significantly associated with tumour size (P =
      0.023) and advanced TNM stage (stage I/II versus stage III, P = 0.039; stage I/II
      versus stage IV, P = 0.027). Moreover, HIF-1alpha expression positively
      correlated with cellular proliferation (P = 0.024) and microvessel density/neo
      angiogenesis (P = 0.038), but not with apoptosis. CONCLUSIONS: HIF-1alpha may
      play a critical role in the progression of pancreatic carcinoma.

PMID- 14636256
TI  - Cystic fibrohistiocytic tumours presenting in the lung: primary or metastatic
      disease?
AB  - AIMS: Cystic fibrohistiocytic tumour of the lung is a rare proliferative process.
      Its histogenesis is uncertain, but evidence suggests that some cases represent
      metastatic disease from apparently indolent skin lesions, namely cellular fibrous
      histiocytomas. This study presents four cases and reviews the literature
      concerning this pattern of disease and its aetiology. METHODS AND RESULTS: All
      patients were male (age range 35-54 years). Two presented with recurrent
      haemoptysis. Two cases had histories of cutaneous fibrohistiocytic lesions in the
      chest wall, excised 10 and 23 years prior to presentation with lung disease.
      Imaging data showed multiple bilateral cystic lung lesions in all four patients
      with nodular cavitating opacities seen on high-resolution computed tomography
      scans. Microscopy showed variably dilated thin-walled cystic airspaces lined by
      cuboidal epithelium and an underlying layer of mildly pleomorphic spindle cells
      with slightly wavy morphology and storiform architecture, admixed with
      inflammatory cells. Tumour cells stained for CD68 in three of four cases. All
      cases were negative for CD34. All patients were alive with disease, although one
      required pneumonectomy for intractable haemoptysis. CONCLUSION: This study and a
      review of published cases show that the majority of cystic fibrohistiocytic
      tumours of the lung probably represent metastases from cellular fibrous
      histiocytomas. However, rare cases may be either primary in origin or the primary
      site remains occult; the term cystic fibrohistiocytic tumour remains appropriate
      for such cases.

PMID- 14636257
TI  - Cathepsin B, D and K expression in adamantinomatous craniopharyngiomas relates to
      their levels of differentiation as determined by the patterns of retinoic acid
      receptor expression.
AB  - AIMS: To investigate the potential predictive value of cathepsins B, D and K in a
      series of 51 adamantinomatous craniopharyngiomas. While almost always benign,
      craniopharyngiomas exhibit a high propensity to recur postsurgically and
      biological markers are therefore needed to predict their recurrence. We have
      previously demonstrated the potential predictive value of retinoic acid receptors
      (RARs) (Lefranc et al., J. Neurosurg. 2003; 98; 145-153). METHODS AND RESULTS:
      Computer-assisted microscopy was used to determine quantitatively the
      immunohistochemical levels of expression of the alpha, beta and gamma RAR
      subtypes and cathepsins B, D and K. The levels of expression of cathepsin D and
      of cathepsin B correlated significantly with the levels of expression of RARbeta.
      The levels of expression of cathepsin K correlated significantly with the levels
      of expression of RARgamma. CONCLUSIONS: Recurrent adamantinomatous
      craniopharyngiomas are characterized by low levels of RARbeta and high levels of
      RARgamma. The tendency to recurrence seems, at least partly, to relate to the
      fact that (i) craniopharyngiomas with low levels of RARbeta express low levels of
      cathepsin D, and (ii) craniopharyngiomas with high levels of RARgamma express
      high levels of cathepsin K.

PMID- 14636258
TI  - The prognostic relevance of estimates of proliferative activity in early breast
      cancer.
AB  - AIMS: Immunohistochemical estimates of cell proliferation evaluated with MIB-1
      antibody have been suggested as prognostic indicators in different types of
      carcinoma. This study investigates whether MIB-1 scores add additional prognostic
      impact when evaluated together with classical clinicopathological parameters at
      diagnosis in early breast cancer patients. MATERIALS AND METHODS: Tumour
      specimens from 365 consecutively treated breast cancer patients were
      immunostained for MIB-1 and evaluated under the microscope using systematic
      random sampling accomplished by the CAST-grid system. RESULTS: The systematic
      random sampling technique resulted in MIB-1 estimates with very high
      interobserver and intraobserver reproducibilities (P < 0.0001). Median MIB-1 was
      16% (range 0-83%). Patients were stratified by MIB-1 in tertiles, and increasing
      MIB-1 was significantly associated with poor overall and disease-specific
      survival in node-positive patients, but not in node-negative patients. High MIB-1
      was significantly related to large tumour size, and strongly associated with high
      grade, high mitotic score, negative oestrogen receptor status and young age. In
      multivariate analysis, both with and without malignancy grade and number of
      mitoses included in the analysis, MIB-1 estimates showed no independent
      prognostic impact. CONCLUSIONS: High MIB-1 estimates did not add independent
      prognostic information at diagnosis when evaluated together with classical
      prognostic markers of early breast cancer.

PMID- 14636259
TI  - Lymph node reticulum cell neoplasm with progression into cytokeratin-positive
      interstitial reticulum cell (CIRC) sarcoma: a case study.
AB  - AIMS: To detail on sequential biopsies the morphological and immunohistochemical
      features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC)
      tumour which progressed into a clinically aggressive cytokeratin-positive
      interstitial reticulum cell (CIRC) sarcoma. METHODS AND RESULTS: A 70-year-old
      female underwent surgical excision of an enlarged submandibular lymph node. The
      nodal architecture was effaced by a neoplastic proliferation of medium to large
      cells, round to oval to spindle in shape, growing in a storiform pattern. The
      tumour stained for vimentin, CD68, factor XIIIa, alpha1-antitrypsin, fascin and
      actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC
      tumour was made by combining pathological and clinical data. The patient received
      no therapy but 5 months later the tumour relapsed, exhibiting a deceptively
      pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense
      p53 expression and aggressive clinical course with fatal outcome. In-situ
      hybridization for Epstein-Barr virus was negative. CONCLUSIONS: We speculate that
      the morphological changes and p53 expression of the relapsing neoplasm might
      reflect tumour cell dedifferentiation, in keeping with the aggressive clinical
      course. The intense p53 expression suggests that this oncoprotein might also play
      a role in reticulum cell tumorigenesis.

PMID- 14636260
TI  - Why do histology on retinal haemorrhages in suspected non-accidental injury?
AB  - The detailed documentation of ocular pathology has become an important component
      in the autopsy investigation of suspected cases of non-accidental injury in
      infants and young children. Careful histological examination of retinal
      haemorrhages is of critical importance, but there remains debate about the
      significance of some findings. This issue has been thrown into sharper relief by
      recent neuropathological studies questioning the mechanisms of some CNS findings.
      To discuss the importance of histological findings in the retina and their
      potential significance and specificity, we have invited contributions from
      authors in the USA and UK.

PMID- 14636261
TI  - Melanoma arising in and limited to a spinal nerve root of the cauda equina.

PMID- 14636262
TI  - Small foci of high-grade carcinoma cells in adenoid cystic carcinoma represent an
      incipient phase of dedifferentiation.

PMID- 14636263
TI  - Cytokeratin-positive malignant solitary fibrous tumour of the pleura: an unusual
      pitfall in the diagnosis of pleural spindle cell neoplasms.

PMID- 14636264
TI  - Ileal intussuseptus containing a Meckel's diverticulum showing florid localized
      mucosal angiogenesis and microcarcinoidosis.

PMID- 14636268
TI  - The role of flat and depressed colorectal lesions in colorectal carcinogenesis:
      new insights from clinicopathological findings in high-magnification chromoscopic
      colonoscopy.
AB  - High-magnification chromoscopic endoscopy is a new technique which has been
      recently introduced to the UK. This technology, initially pioneered by the
      Japanese in the 1980s, has changed our understanding of the pathogenesis of
      colorectal cancer and our subsequent therapeutic strategies aimed at the
      secondary prevention of cancer. Magnification colonoscopic techniques when
      combined with colonic chromoscopy (dye spraying of the colon) permit in vivo
      assessments of lesions at a magnification and resolution similar to a
      stereomicroscope. Furthermore, flat/depressed adenomas and cancers can be
      diagnosed with increasing frequency and new resection practices performed. This
      technique is known as endoscopic mucosal resection. As gastrointestinal
      endoscopists adopt these new techniques, close liaison with histopathologists is
      essential to provide the highest standards of diagnostic accuracy. The
      histopathologist also needs to be aware of the endoscopic findings when
      interpreting specimens and hence must understand new endoscopic terminologies and
      classification systems that accompany the introduction of new technologies and
      therapeutic techniques. This article describes the controversies relating to the
      flat and depressed colorectal lesion, where these new endoscopic technologies are
      ideally suited. It then provides a working description of high-magnification
      chromoscopic colonoscopy including the Japanese 'pit pattern' and morphological
      classification system-information which will be provided to histopathologists
      with specimens obtained by these new techniques. Finally, we describe the
      procedure of endoscopic mucosal resection, as the type and quality of specimens
      received for histopathological analysis will be highly influenced by these
      techniques.

PMID- 14636270
TI  - 'Pseudomesotheliomatous' carcinomas of the pleura: a 10-year analysis of cases
      from the Environmental Lung Disease Research Group, Cardiff.
AB  - AIMS: To undertake a clinicopathological study of diffuse serosal neoplasms of
      epithelial histogenesis which clinically and pathologically mimic malignant
      pleural mesothelioma. METHODS AND RESULTS: Over a 10-year (1990-2000) study
      period 53 carcinomas mimicking diffuse pleural mesothelioma
      ('pseudomesotheliomatous' carcinoma) were identified. The study group comprised
      50 men and three females, age range 33-77 (median 68) years. In 46 (87%) cases
      there was a history of smoking and in 40 (76%) cases a history of asbestos
      exposure. Histologically the pleural 'pseudomesotheliomatous' carcinomas could be
      divided into two broad groups: primary pulmonary carcinomas with florid
      pleurotropic growth (n = 47), of which 34 (70%) were adenocarcinomas; and diffuse
      carcinomatous involvement of the pleura by metastatic tumour (n = 6). This latter
      group comprised two transitional cell carcinomas of bladder, one renal (clear)
      cell carcinoma, one ductal pancreatic adenocarcinoma, one prostatic
      adenocarcinoma and one squamous cell carcinoma of parotid gland origin. Follow-up
      data were available in 35 cases. Regardless of tumour type, survival was poor
      (median 8 months) and comparable to diffuse pleural mesothelioma. CONCLUSIONS:
      Pleural 'pseudomesotheliomatous' carcinomas are uncommon (comprising 6% of
      referrals), pathologically heterogeneous tumours with poor prognosis. Tissue
      diagnosis should be obtained in all cases of suspected diffuse pleural neoplasia.
      By light microscopy and immunophenotype many of the tumours mimicked malignant
      mesothelioma. In particular, an awareness that all neoplasms exhibiting squamous
      differentiation may express cytokeratin 5/6 and thrombomodulin is important to
      prevent misinterpretation. In this respect, calretinin is regarded as the most
      specific and sensitive mesothelial marker. Misdiagnosis may have medico-legal
      implications in asbestos-related compensation claims.

PMID- 14636269
TI  - Tumour cell and stromal features in metastatic and non-metastatic non-small cell
      lung carcinomas.
AB  - AIMS: Tumour cell behaviour depends on the interactions between nuclear genetic
      changes in the malignant cells and a stroma favourable for growth, invasion and
      metastasis. To evaluate such interactions, we studied the relationship between
      tumour cell and stromal features for proliferative factors, p53, microvessel
      density and metalloproteinases, controlled for the extent of the primary lesion
      (T1 to T4), in early (non-metastatic) and late (metastatic) non-small cell lung
      carcinomas (NSCLC). METHODS AND RESULTS: Variables were examined for differences
      and correlations in the frequency of p53, AgNOR, CD34 and MMP-9 expression in
      primary lesions and metastases of NSCLC using a general linear model. The
      patients included 58 males and 22 females (mean age 62 +/- 9 years) with 19 T1
      (23.8%), 40 T2 (50.0%), 14 T3 (17.5%) and seven T4 (8.8%). In late disease, AgNOR
      and p53 were statistically related to the extent of the primary lesion, whereas
      in early disease AgNOR tended to be increased in tumours without metastasis,
      while p53 expression tended to decrease progressively in tumours with metastasis.
      Microvessel density in late disease was of no statistical significance, whereas
      in early disease strong CD34 expression was seen in tumours with metastasis,
      being at its maximum in T3 primary lesions. The best marker for the extent of the
      lesion and its progression was MMP-9, with greater expression by tumours with
      metastasis than those without. CONCLUSIONS: Different tumour cell and stromal
      interactions control metastasis and therefore the biological risk of NSCLC. A
      panel of molecular markers, such as p53, MMP-9 and CD34 could help to identify
      subgroups of patients that could benefit from adjuvant therapy.

PMID- 14636271
TI  - Cytokeratin 7/20 and mucin expression patterns in oesophageal, cardia and distal
      gastric adenocarcinomas.
AB  - AIMS: The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6
      immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ)
      adenocarcinomas. The aim was to compare expression patterns in these locations as
      aids to accurate classification of these morphologically similar carcinomas which
      all may involve the GOJ. METHODS AND RESULTS: Tissue microarrays were constructed
      using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections
      were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of
      this study showed no differences in CK7 and CK20 expression patterns in the three
      locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ
      and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of
      oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was
      associated with higher pTNM-stage. CONCLUSIONS: CK 7/20 profiles have no role in
      distinguishing tumours of the three locations. Mucin expression patterns differed
      in oesophageal and gastric adenocarcinomas, although not sufficiently to classify
      individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was
      partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a
      higher pTNM stage.

PMID- 14636272
TI  - ALK-negative anaplastic large-cell lymphoma demonstrates similar poor prognosis
      to peripheral T-cell lymphoma, unspecified.
AB  - AIMS: Anaplastic large cell lymphoma (ALCL) is classically considered a
      clinicopathological entity separate from other nodal mature T-cell lymphomas
      (TCL). Recently, the anaplastic lymphoma kinase (ALK) protein was shown to
      identify a subgroup of nodal ALCL with an excellent prognosis, whereas ALK
      negative ALCLs are more heterogeneous. The aim of this study was to investigate
      the clinicopathological parameters in relation to clinical behaviour of ALK
      negative ALCL compared with other nodal mature TCL, i.e. peripheral TCL,
      unspecified (PTCL-NOS) and angioimmunoblastic lymphoma (AILT). METHODS AND
      RESULTS: Clinicopathological data of ALK-positive (n = 28) and ALK-negative (n =
      46) ALCL; PTCL-NOS (n = 47); and AILT (n = 12) were analysed for their prognostic
      significance. While ALK-positive ALCL shows favourable clinical features and a
      good prognosis, ALK-negative ALCL, PTCL-NOS and AILT are all associated with high
      age groups, advanced disease stage, and poor prognosis (<45% 5-year survival). In
      multivariate analysis of overall survival time, performed in the combined group
      of ALK-negative nodal mature T-cell lymphomas, only age and the International
      Prognostic Index (IPI) remained independent prognostic parameters, while lymphoma
      subtype (ALCL versus PTCL-NOS versus AILT) gave no additional information.
      CONCLUSIONS: The distinction between ALK-negative ALCL and PTCL-NOS or AILT is of
      limited clinical relevance as they show comparable poor prognosis. In these
      lymphoma subtypes, only age and the IPI are of significant prognostic value.

PMID- 14636273
TI  - Bone marrow histopathology following cytoreductive therapy in chronic idiopathic
      myelofibrosis.
AB  - AIMS: To analyse systematically therapy-induced lesions of haematopoiesis in
      chronic idiopathic myelofibrosis (IMF). METHODS AND RESULTS: A total of 759
      sequential bone marrow (BM) biopsies (median interval 32 months) were performed
      in 261 patients with IMF. Besides a control group (symptomatic treatment),
      monotherapies included busulfan, hydroxyurea and interferon. In all therapy
      groups hypoplasia of varying degree was a frequent finding and often accompanied
      by a patchy distribution of haematopoiesis. Most conspicuous was gelatinous
      oedema showing a tendency to develop discrete reticulin fibrosis (scleroedema).
      Minimal to moderate maturation defects of megakaryopoiesis and erythroid
      precursors occurred, but overt myelodysplastic features were most prominent
      following hydroxyurea and busulfan therapy. Acceleration and blastic crisis were
      characterized by the appearance of immature and CD34+ progenitor cells.
      Concerning the dynamics of fibrosis, no differences were observed between
      controls and the various therapy groups. In 143 patients (55%) without or with
      little reticulin at onset, an increase in myelofibrosis was detectable that
      progressed to overt collagen fibrosis. CONCLUSIONS: Therapy-related bone marrow
      lesions in IMF comprise a strikingly variable spectrum that may include aplasia
      with scleroedema and a patchy distribution of myelodysplastic haematopoiesis
      associated with progressive myelofibrosis.

PMID- 14636274
TI  - MOC-31/Ep-CAM immunoreactivity in Merkel cells and Merkel cell carcinomas.
AB  - AIMS: To evaluate the monoclonal antibody MOC-31 in Merkel cell carcinomas and
      normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that
      occurs mainly in elderly individuals. The histological diagnosis of Merkel cell
      carcinoma can be difficult because it looks similar to other small blue cell
      tumours, particularly skin metastases of small-cell lung carcinomas. This
      antibody recognizes the epithelial cell adhesion molecule (Ep-CAM), that has been
      assigned to the small cell lung cancer cluster 2 of antibodies. To the best of
      our knowledge, immunostaining for MOC-31/Ep-CAM has not been previously described
      in Merkel cells or Merkel cell carcinomas. METHODS AND RESULTS: Thirty-one cases
      of Merkel cell carcinoma and three samples of normal human fingertip were
      selected to analyse the expression of MOC-31/Ep-CAM by immunohistochemistry. A
      high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily
      interpretable positivity. Immunostaining was diffuse or focal and always
      localized to the plasma membrane. Normal Merkel cells of human fingertip also
      showed plasma membrane immunoreactivity for MOC-31/Ep-CAM. CONCLUSION: The
      demonstration of positivity for MOC-31/Ep-CAM in Merkel cell carcinomas precludes
      the use of this immunohistochemical marker to distinguish between tumours and
      skin metastases of small-cell lung carcinoma.

PMID- 14636276
TI  - Cytokeratin-positive interstitial cell neoplasm: a case report and classification
      issues.
AB  - AIMS: Tumours of dendritic/accessory cell origin are rare neoplasms arising in
      lymph nodes. Among these, tumours derived from cytokeratin-positive interstitial
      reticulum cells (CIRCs), a subset of fibroblastic reticulum cells, are reported
      even less frequently. The International Lymphoma Study Group (ILSG) has recently
      proposed a classification for tumours of histiocytes and accessory dendritic
      cells in which CIRC tumours are not included. We report a case of a CIRC tumour
      arising in a submandibular lymph node of a 66-year-old male. METHODS AND RESULTS:
      The neoplasm was composed of spindle cells with elongated or round nuclei,
      prominent nucleoli and abundant cytoplasm. These cells were arranged in a diffuse
      fascicular and vaguely whorled pattern. The tumour cells stained diffusely for
      S100, vimentin, desmin, lysozyme, and focally for CD68 and cytokeratins 7, 8, 18,
      CK-AE1 and CK-pool. Electron microscopy was performed for further evaluation on
      samples taken from the paraffin block; this revealed cytoplasmic projections and
      rudimentary cell junctions. CONCLUSIONS: Histopathologist should be aware of the
      existence of tumours deriving from CIRCs, as these cases may be misdiagnosed as
      metastatic carcinoma. Careful clinical and pathological evaluation is necessary
      to exclude this possibility.

PMID- 14636275
TI  - Minichromosome maintenance protein 7 expression in gestational trophoblastic
      disease: correlation with Ki67, PCNA and clinicopathological parameters.
AB  - AIMS: To assess the proliferative activity of gestational trophoblastic disease
      (GTD) using one of the novel proliferation markers (MCM7) and to determine its
      prognostic value in hydatidiform mole (HM). METHODS AND RESULTS:
      Immunohistochemical staining for MCM7 was performed on 122 samples of paraffin
      embedded trophoblastic tissues including 22 normal first-trimester placentas, 12
      term placentas, 12 spontaneous miscarriages (SM), 21 partial moles (PM), 44
      complete hydatidiform moles (CM), and 11 choriocarcinomas (CCA). The correlations
      between the proliferative indices assessed by MCM7, proliferating cell nuclear
      antigen (PCNA) and Ki67 (MIB1) immunoreactivity as well as clinical progress were
      assessed. MCM7 immunoreactivity was found predominantly in the nuclei of
      cytotrophoblast and intermediate trophoblast and decreased with placental
      maturation. MCM7 expression was highest in CCA, followed by CM, PM, normal first
      trimester placenta, SM and term placenta. MCM7 index was significantly higher in
      PM and CM than in SM (P = 0.007, P < 0.001) but not between PM and CM themselves
      (P = 0.560). Eighteen of the 65 patients with HM developed persistent
      trophoblastic disease (PTD) requiring chemotherapy. There was no significant
      difference in MCM7 indices between the patients who developed PTD and those who
      did not (P = 0.312). MCM7 indices correlated well with Ki67 (P = 0.002) but not
      with PCNA (P = 0.054) indices. MCM7 indices demonstrated less variability than
      PCNA and Ki67 and may be a better proliferation marker than the latter two.
      CONCLUSIONS: We conclude that MCM7 is useful in differentiating molar and non
      molar gestations but is not helpful in discriminating PM from CM or in predicting
      PTD.

PMID- 14636277
TI  - Clear cell struma ovarii.

PMID- 14636278
TI  - A migrating granuloma.

PMID- 14636279
TI  - Malignant epithelioid mesothelioma of the pleura with hyaline globules.

PMID- 14636280
TI  - High-grade thymic carcinoma other than basaloid or mucoepidermoid type could be
      associated with multilocular thymic cyst: report of two cases.

PMID- 14636281
TI  - Brenner tumour with carcinoma in situ: evidence for a spectrum from benign to
      malignant.

PMID- 14636282
TI  - Frozen section diagnosis of fibrotic sclerosing pneumocytoma with psammomatous
      calcification.

PMID- 14636284
TI  - Chronic fatigue syndrome: an endocrine disease off limits for endocrinologists?
AB  - Endocrinologists were not included in the multidisciplinary working groups that
      prepared two recent reports on chronic fatigue syndrome, despite its unequalled
      clinical overlap with Addison's disease, which is a classic endocrine disorder.
      The failure to include at least one endocrinologist in those panels may explain
      why in their extensive reports there is not a single word about the 42 clinical
      features that chronic fatigue syndrome shares with Addison's disease, including
      all the signs and symptoms listed in the case definition of this syndrome.

PMID- 14636285
TI  - A functional variant of the iNOS gene flanking region is associated with LAD
      coronary artery disease: an autopsy study.
AB  - BACKGROUND: Recent studies using reporter gene constructs have indicated
      significant differences in the promoter activity of inducible nitric oxide
      synthase (iNOS) gene variants. Although the exact role of iNOS in atherogenesis
      is unclear, it is possible that this variation site may influence the extent of
      coronary artery disease (CAD). METHODS: We amplified these (AAAT) repeat variants
      from the NOS2A gene (denoted iNOS R4 and iNOS R5) from 325 Finnish men included
      in the Helsinki Sudden Death Study, and studied their association with indices of
      stenosis and atherosclerosis of the left anterior descending artery (LAD), right
      coronary artery (RCA) and left circumflex artery (LCX). In order to understand
      the effect of iNOS genotype on different stages of CAD, our study population was
      divided into age groups. RESULTS: In the LAD, the progression of atherosclerosis
      seemed to be more pronounced in the 4/5 genotype carriers than in those with the
      4/4 genotype when the different age groups were compared. More specifically,
      statistically significant differences between the genotypes were found in the
      subgroup of men aged > 55 years. In this group, men carrying the rare R4/5
      genotype presented higher mean values of stenosis percentages (55% vs. 42%, P =
      0.008), larger areas of fatty streaks (10.4% vs. 5.9%; P = 0.01) and complicated
      lesions (3.5% vs. 1.3%; P = 0.001) compared with the R4/4 carriers. No
      significant association of iNOS genotypes with stenosis and atherosclerosis of
      RCA and LCX was found. CONCLUSIONS: It appears unlikely the R4/5 genotype plays a
      major role in the pathogenesis of CAD, as it was not associated with stenosis and
      atherosclerosis in RCA and LCX. However this genotype may have some role in more
      pronounced CAD, as seen in the LAD.

PMID- 14636286
TI  - Effect of iron sucrose on human peritoneal mesothelial cells.
AB  - BACKGROUND: Iron supplementation is often required in uraemic patients with
      anaemia. Peritoneal cavity was proposed as an alternative intravenous route for
      iron infusion in patients treated with peritoneal dialysis. We studied the effect
      of iron sucrose (Venofer) on the function of human peritoneal mesothelial cells
      maintained in in vitro culture. MATERIALS AND METHODS: In in vitro experiments on
      human peritoneal, the mesothelial effect of elemental iron (in conc. 0.0001-1 mg
      mL-1) present in Venofer on their viability, growth and synthesis of IL-6 was
      studied. Additionally we evaluated with a fluorescent probe (2',7'
      dichlorodihydro-fluorescein diacatate) generation of reactive oxygen species in
      cells exposed to iron sucrose. We also measured accumulation of iron in the
      cytoplasm of mesothelial cells after their in vitro exposure to Venofer. RESULTS:
      In in vitro conditions iron induces a dose-dependent inhibition of viability of
      the mesothelial cells as reflected by inhibition of the cells growth by 34% at Fe
      0.1 mg mL-1 vs. control (P < 0.05) increased release of lactate dehydrogenase
      (LDH) from the cytosol: 67.1 +/- 30.3 mU mL-1 at Fe 1 mg mL-1 vs. 7.9 +/- 6.4 in
      control group (P < 0.001), and reduced synthesis of IL-6: 209 +/- 378 pg mg-1
      cell protein at Fe 1 mg mL-1 vs. 38674 +/- 4146 pg mg-1 cell protein in controls
      (P < 0.001). Cytotoxicity of iron towards mesothelial cells was enhanced in vitro
      when it was tested in presence of the dialysis fluid. Iron used in vitro at
      concentration 0.0001 mg mL-1 and greater induces generation of oxygen-derived
      free radicals in mesothelial cells. Furthermore, iron is taken by these cells and
      stored in their cytosol, resulting in stimulation of the intracellular generation
      of free radicals. CONCLUSIONS: We conclude that iron used in the form of iron
      sucrose is cytotoxic to human peritoneal mesothelial cells. Accumulation of iron
      sucrose within cytoplasm of these cells may lead to induction of its chronic
      cytotoxic effect.

PMID- 14636287
TI  - Lipoprotein (a) and acute-phase response in patients with vestibular neuronitis.
AB  - BACKGROUND: Vestibular neuronitis (VN) is a relatively common condition
      characterized by the acute onset of vertigo, nausea and vomiting, in the absence
      of auditory or central nervous system involvement. The exact aetiology
      (inflammatory, viral or vascular?) remains obscure. Lipoprotein (a) [Lp(a)] is an
      atherogenic particle. Its serum levels are mainly genetically determined and vary
      widely between individuals. Whether Lp(a) is consistently a positive acute-phase
      reactant is controversial. PURPOSE: We evaluated the alterations in lipidaemic
      parameters and serum biological markers (including acute-phase reactants) in
      adult patients presenting acutely with VN. SUBJECTS AND METHODS: A total of 34
      consecutive VN patients (24 men and 11 women) and 37 apparently healthy controls
      (25 men and 12 women) were studied. Laboratory evaluation was performed during
      the acute episode and 6 months later (stable state). RESULTS: Serum Lp(a)
      concentrations were significantly lower at the time of presentation (median value
      6.4 vs. 16.4 mg dL-1 in the stable state, P < 0.001), whereas fibrinogen levels
      were significantly higher during the acute episode than in the stable state
      (median value 293.0 vs. 202.0 mg dL-1, respectively, P < 0.0001). During the
      acute episode, plasma fibrinogen correlated with CRP levels (Spearman r = 0.84, P
      < 0.0001). By contrast, inverse correlations were noted between Lp(a) levels and
      CRP (Spearman r = -0.47, P = 0.007) as well as between Lp(a) and fibrinogen
      levels (Spearman r = -0.35, P = 0.05). CONCLUSION: Vestibular neuronitis episodes
      are associated with evidence of an acute inflammatory response as reflected by
      significant elevations in plasma fibrinogen and CRP concentrations, whereas Lp(a)
      behaves as a negative acute-phase reactant.

PMID- 14636288
TI  - Alterations in high-density lipoprotein metabolism and reverse cholesterol
      transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic
      enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins.
AB  - Insulin resistance and type 2 diabetes mellitus are generally accompanied by low
      HDL cholesterol and high plasma triglycerides, which are major cardiovascular
      risk factors. This review describes abnormalities in HDL metabolism and reverse
      cholesterol transport, i.e. the transport of cholesterol from peripheral cells
      back to the liver for metabolism and biliary excretion, in insulin resistance and
      type 2 diabetes mellitus. Several enzymes including lipoprotein lipase (LPL),
      hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT), as well as
      cholesteryl ester transfer protein (CETP) and phospholipid transfer protein
      (PLTP), participate in HDL metabolism and remodelling. Lipoprotein lipase
      hydrolyses lipoprotein triglycerides, thus providing lipids for HDL formation.
      Hepatic lipase reduces HDL particle size by hydrolysing its triglycerides and
      phospholipids. A decreased postheparin plasma LPL/HL ratio is a determinant of
      low HDL2 cholesterol in insulin resistance. The esterification of free
      cholesterol by LCAT increases HDL particle size. Plasma cholesterol
      esterification is unaltered or increased in type 2 diabetes mellitus, probably
      depending on the extent of triglyceride elevation. Subsequent CETP action results
      in transfer of cholesteryl esters from HDL towards triglyceride-rich
      lipoproteins, and is involved in decreasing HDL size. An increased plasma
      cholesteryl ester transfer is frequently observed in insulin-resistant
      conditions, and is considered to be a determinant of low HDL cholesterol.
      Phospholipid transfer protein generates small pre beta-HDL particles that are
      initial acceptors of cell-derived cholesterol. Its activity in plasma is elevated
      in insulin resistance and type 2 diabetes mellitus in association with high
      plasma triglycerides and obesity. In insulin resistance, the ability of plasma to
      promote cellular cholesterol efflux may be maintained consequent to increases in
      PLTP activity and pre beta-HDL. However, cellular cholesterol efflux to diabetic
      plasma is probably impaired. Besides, cellular abnormalities that are in part
      related to impaired actions of ATP binding cassette transporter 1 and scavenger
      receptor class B type I are likely to result in diminished cellular cholesterol
      efflux in the diabetic state. Whether hepatic metabolism of HDL-derived
      cholesterol and subsequent hepatobiliary transport is altered in insulin
      resistance and type 2 diabetes mellitus is unknown. Specific CETP inhibitors have
      been developed that exert major HDL cholesterol-raising effects in humans and
      retard atherosclerosis in animals. As an increased CETP-mediated cholesteryl
      ester transfer represents a plausible metabolic intermediate between high
      triglycerides and low HDL cholesterol, studies are warranted to evaluate the
      effects of these agents in insulin resistance- and diabetes-associated
      dyslipidaemia.

PMID- 14636289
TI  - Genome-wide screen in obese pedigrees with type 2 diabetes mellitus from a
      defined Dutch population.
AB  - A genome scan was performed in obese type 2 diabetes mellitus pedigrees to
      identify susceptibility loci involved in obesity-driven type 2 diabetes mellitus.
      We studied the 20% most obese diabetes pedigrees from a confined Dutch population
      from around the town of Breda. Previously we, and others, have already shown that
      a susceptibility locus influencing obesity in diabetes may reside on chromosome
      18p11. We now report evidence to also suggest linkage for type 2 diabetes in
      these obese pedigrees on chromosome regions 11p (genome-wide P-value </= 0.061)
      and 12q (genome-wide P-value </= 0.029), thereby confirming previous findings
      from corresponding regions. The linkage found in the Breda Cohort of type 2
      diabetes patients is influenced by obesity. This supports the notion that a
      genetic predisposition to obesity is probably intertwined with a genetic
      predisposition to type 2 diabetes. Further efforts should address the question of
      how, on a genetic level, these two factors interact.

PMID- 14636290
TI  - Aortic distensibility is reduced in subjects with type 2 diabetes and cardiac
      autonomic neuropathy.
AB  - BACKGROUND: Reduced aortic distensibility predicts cardiovascular mortality in
      patients with type 2 diabetes and impaired glucose tolerance. Cardiac autonomic
      neuropathy is common in subjects with diabetes. However, the relationship between
      the elastic properties of the aorta and autonomic neuropathy has not been studied
      to date in subjects with type 2 diabetes. MATERIALS AND METHODS: In this cross
      sectional study, a total of 87 subjects with type 2 diabetes (27 with and 60
      without cardiac autonomic neuropathy) as well as 60 healthy individuals, matched
      for age and sex with the diabetic subjects, were examined. Cardiac autonomic
      neuropathy was diagnosed on the basis of the battery of the classic
      cardiovascular autonomic function tests. Aortic distensibility was assessed by
      high-resolution ultrasonography. RESULTS: Diabetic patients had reduced aortic
      distensibility in comparison with the control subjects: 1.81 +/- 0.58 vs. 2.53 +/
      0.34 10-6 cm2 dyn-1, respectively (P < 0.0001). In addition, diabetic
      individuals with cardiac autonomic neuropathy had reduced aortic distensibility
      as compared with patients without this complication: 1.60 +/- 0.72 vs. 1.90 +/-
      0.48 10-6 cm2 dyn-1, respectively (P = 0.02). Multivariate linear regression
      analysis in the diabetic group, after controlling for a number of confounding
      factors such as age, systolic and diastolic blood pressure, duration of diabetes
      and presence as well as severity of cardiac autonomic neuropathy, demonstrated a
      significant and independent association between duration of diabetes [B = -0.02,
      SE(B) = 0.01, P = 0.01] and presence of cardiac autonomic neuropathy [B = -0.29,
      SE(B) = 0.14, P = 0.03] with aortic distensibility. CONCLUSION: Type 2 diabetes
      is associated with a significant reduction in the elastic properties of the
      aorta. In addition, known duration of diabetes and presence of cardiac autonomic
      neuropathy are the main predictors of aortic distensibility in subjects with type
      2 diabetes.

PMID- 14636291
TI  - Gender, age and menopause effects on the prevalence and the characteristics of
      obstructive sleep apnea in obesity.
AB  - BACKGROUND: In the 1970s and 80s it was believed that obstructive sleep apnea
      (OSA) was primarily a disease of men. The present study was addressed to evaluate
      the effect of gender and menopause on the prevalence and the characteristics of
      OSA and on anthropometric, clinical, respiratory and polysomnographic data in a
      population of obese individuals. PATIENTS AND METHODS: A total of 230 obese
      subjects (BMI >/= 30 kg m-2), 148 women and 82 men, aged 16-75 years, were
      recruited and evaluated for general and anthropometric parameters, respiratory
      function, sleep-related symptoms and sleep disorders of breathing. RESULTS:
      Respiratory disturbance index (RDI) and the prevalence of OSA were lower in women
      than in men (P < 0.001 and P < 0.001, respectively). Among subjects < 55 years,
      neck circumference, percentage of predicted normal neck circumference (PPNC),
      waist-to-hip ratio (WHR), PaCO2, RDI and the prevalence of OSA were lower in
      female subjects (P = 0.05, P < 0.05, P < 0.001, P < 0.01 and P < 0.01,
      respectively). BMI, neck circumference, PPNC, WHR, RDI and the prevalence of OSA
      were higher in postmenopausal compared with premenopausal women (P < 0.01, P <
      0.01, P < 0.01, P < 0.01 and P < 0.01, respectively). CONCLUSIONS: Our study
      demonstrates that (i) the male dominance regarding the prevalence and the
      severity of OSA disappears in men older than 55 years, and (ii) menopause seems
      to play a pivotal role in modulating both the presence and the degree of sleep
      disorder.

PMID- 14636292
TI  - Nasal nitric oxide measurements before and after repeated humming maneuvers.
AB  - BACKGROUND: It has been recently shown that humming greatly increases nasal
      nitric oxide (NO). This is most likely owing to a rapid washout of sinus NO
      caused by the oscillating sound waves. During repeated humming manoeuvres nasal
      NO gradually decreases, likely because NO accumulated in the sinuses is washed
      out. AIM: We studied whether humming before measurements would affect nasally
      exhaled NO. MATERIALS AND METHODS: NO output was measured by the
      chemiluminescence technique in orally and nasally exhaled air in 38 subjects: 18
      healthy subjects (HS), 15 subjects with allergic rhinitis (AR) and five subjects
      with allergic nasal polyposis (AP). Each subject performed a NO measurement
      during quiet nasal exhalation either preceded by a period of silence/free
      speaking or immediately after five consecutive humming manoeuvres (posthumming).
      RESULTS: Mean nasal NO output (95% CI) after a period of silence/free speaking
      was 231 nL min-1 (178-284) in HS, 434 nL min-1 (347-522) in AR (P < 0.001) and
      262 nL min-1 (163-361) in AP. Post-humming nasal NO output was 16% (5 to 50%)
      lower in HS and 14% (1 to 49%) lower in AR, while it remained unchanged in AP
      subjects. Intra-subject coefficient of variation of quiet nasal exhalation was
      12% in HS, 13% in AR and 5% in AP. Post humming intraindividual coefficient of
      variation significantly decreased in both HS and AR, but it did not change in AP.
      CONCLUSIONS: Nasal NO levels measured immediately after repeated humming
      manoeuvres are consistently lower and more reproducible than nasal NO levels
      measured after a period of silence or free speaking. Repeated humming effectively
      empties the sinuses, thereby probably minimizing the normal contribution from the
      sinuses to nasal NO. This may be useful to better estimate NO output from the
      nasal cavity mucosa in health and disease.

PMID- 14636293
TI  - Incorrect and inconsistent use of homocysteine's nomenclature: a potential source
      of misunderstandings.

PMID- 14636295
TI  - Mechanisms of nitrate tolerance: potential roles of folate.
AB  - More than 100 years since their introduction in cardiovascular therapy, nitrates
      continue to be widely used in ischaemic heart disease despite incomplete
      knowledge of their intimate mechanism of action. Particularly, the development of
      a progressive attenuation of their efficacy over prolonged use (tolerance)
      continues to be the subject of current investigation. Newer findings point to the
      role of increased intracellular oxidative stress as a mechanism for tolerance and
      to folic acid derivatives as pharmacologic means to attenuate its development.
      This paper reviews nitrate mechanism of action, the history of nitrate tolerance
      and newer findings related to the use of folate to prevent this phenomenon.

PMID- 14636296
TI  - Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand
      factor, tissue factor and vascular endothelial growth factor levels in congestive
      heart failure.
AB  - BACKGROUND: Congestive heart failure (CHF) carries a poor prognosis with a high
      mortality rate, frequent hospitalizations and increased risk of thrombotic
      complications such as stroke. Cytokines may contribute to the progression and
      prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6)
      and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which
      are raised in CHF. The procoagulant properties of both cytokines may be mediated
      via tissue factor (TF), a potent clotting activator. We hypothesized that plasma
      levels of these markers, as well as levels of plasma viscosity, fibrinogen,
      soluble P-selectin and von Willebrand factor (markers of abnormal rheology,
      clotting, platelet activation, and endothelial damage, respectively) will be
      useful in predicting morbidity and mortality in chronic stable CHF. METHODS AND
      RESULTS: One hundred and twenty consecutive out-patients with chronic stable CHF
      (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection
      fraction of 29 [6]%) were recruited and followed for 2 years during which 42
      patients reached a clinical end-point of all-cause mortality and cardiovascular
      hospitalizations, including stroke and myocardial infarction. Plasma IL-6
      (P=0.003) and TF (P=0.013) levels, but not other research indices, were higher in
      those who suffered events compared with those without events. Predictors of end
      points were high (> or =median) TF (P=0.011), and IL-6 (P=0.023) levels, as well
      as the lowest quartile of a left ventricular ejection fraction (P=0.007). A
      strong correlation was present between TF and IL-6 levels (r=0.59; P<0.0001) and
      with VEGF levels (r=0.43; P<0.0001). CONCLUSION: IL-6 and TF are predictors of
      poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to
      the progression and thrombotic complications of CHF via its actions on TF
      expression. Although VEGF did not independently predict outcome in chronic CHF,
      the possibility arises that it may act with IL-6 to induce TF expression.

PMID- 14636297
TI  - Aortic stiffness and carotid intima-media thickness: two independent markers of
      subclinical vascular damage in young adults?
AB  - BACKGROUND: Previous reports have shown that carotid intima-media thickness
      (CIMT) and arterial stiffness are strong predictors of subsequent cardiovascular
      disease (CVD) morbidity and mortality, and are well related to an unfavourable
      cardiovascular risk profile in middle-aged and older subjects. These similarities
      suggest that arterial stiffness may play a role in the development of
      atherosclerosis or vice versa. However, studies show conflicting results and are
      limited to elderly subjects. To study this issue further, we evaluated the
      relation of arterial stiffness to subclinical atherosclerosis in 524 healthy
      young adults, aged 27-30 years. METHODS AND RESULTS: Aortic stiffness was
      assessed using pulse wave velocity (PWV) and CIMT was used as measure of
      subclinical atherosclerosis. The positive crude correlation between for mean
      arterial pressure adjusted PWV and CIMT (Pearson's correlation coefficient: 0.11;
      P=0.016) attenuated after adjustment for common determinants of both measurements
      like gender and age (partial correlation coefficient: 0.03; P=0.512).
      Furthermore, multivariate linear regression models showed that male gender, age
      and blood pressure were independent determinants of both CIMT and PWV while body
      mass index and LDL-cholesterol were independent determinants of CIMT only.
      CONCLUSIONS: These observations suggest that in healthy young adults arterial
      stiffness and CIMT reflect two separate entities of vascular damage.

PMID- 14636298
TI  - Significant dominance of fibrinogen over immunoglobulins, C-reactive protein,
      cholesterol and triglycerides in maintaining increased red blood cell
      adhesiveness/aggregation in the peripheral venous blood: a model in
      hypercholesterolaemic patients.
AB  - BACKGROUND: It is not clear what is the relative importance of fibrinogen,
      immunoglobulins, highly sensitive C-reactive protein (hs-CRP), cholesterol and
      triglyceride concentrations on the appearance of aggregated red blood cells in
      the peripheral blood. DESIGN: Six hypercholesterolaemic patients undergoing
      regular LDL apheresis that were examined repeatedly before and following the
      procedure. RESULTS: We determined the degree of erythrocyte
      adhesiveness/aggregation in relation to the concentration of the above-mentioned
      macromolecules in 80 samples. In a linear logistic regression the respective R2
      values for fibrinogen, total cholesterol, triglycerides, hs-CRP, IgG, IgM and IgA
      were 0.45 (P<0.0001), 0.2 (P<0.0001), 0.02 (P=0.02), 0.001 (P=NS) and 0.002
      (P=NS), respectively. We further analyzed the potential of ApoA, ApoB and Lpa to
      participate in red cell adhesiveness/aggregation and found them to be not
      significant. CONCLUSIONS: In a milieu of adhesive macromolecules, lipids and
      inflammation-sensitive proteins including fibrinogen, total cholesterol,
      triglycerides, hs-CRP and immunoglobins G, M and A, fibrinogen has a dominant
      role in maintaining the red blood cell adhesiveness/aggregation in the peripheral
      venous blood. These findings are relevant for the research directed at finding
      new apheretic modalities to reduce the degree of red blood cell
      adhesiveness/aggregation in the peripheral blood.

PMID- 14636299
TI  - Low concentrations of intravenous polygelines promote low-molecular weight
      proteinuria.
AB  - BACKGROUND: Previously we observed that atrial natriuretic peptide (ANP)-induced
      albuminuria was accompanied by an increase in urinary excretion of the low
      molecular weight protein (LMW protein) beta2-microglobulin (beta2-m), suggesting
      that the albuminuria may at least partly be the result of blockade of tubular
      protein reabsorption. However, in our experiments ANP was dissolved in the
      polygeline Haemaccel (Hoechst, Behring-Werke, Marburg Germany) to prevent
      adhesion of ANP to the infusion system. Anecdotal reports have shown that high
      dosages of polygelines such as Haemaccel or Gelofusine (Braun NPBI Oss, the
      Netherlands) may influence tubular protein handling. In the present study we have
      evaluated the effect of a low and high doses of the polygeline Haemaccel on
      proteinuria. In addition, we have reassessed the effects of ANP. MATERIALS AND
      METHODS: We measured urinary beta2-microglobulin (beta2-m) and albumin excretion
      in healthy volunteers after infusion of a high-dose pure Haemaccel (0.04 mL kg(
      1) min(-1) for 60 min), a low-dose Haemaccel (0.01 mL kg(-1) min(-1) for 60 min
      followed by infusion of 0.02 mL kg(-1) min(-1) for 60 min) and a low-dose
      Gelofusine (dose comparable to the low-dose Haemaccel). In addition we performed
      similar studies using ANP dissolved in saline and Haemaccel. RESULTS: Infusion of
      Haemaccel caused a dose-dependent increase in urinary excretion of beta2-m. There
      were no differences between Haemaccel and Gelofusine. After infusion of ANP
      dissolved in Haemaccel urinary beta2-m excretion increased from 0.05 +/- 0.03
      microg min(-1) to 27 +/- 10 microg min(-1) and urinary albumin excretion
      increased from 4.5 +/- 1.1 microg min(-1) to 9.7 +/- 6.3 microg min(-1) (P<0.05).
      During ANP + saline infusion, urinary beta2-m excretion did not change, whereas
      the urinary albumin excretion increased from 5.3 +/- 1.5 microg min(-1) to 7.9 +/
      2.4 microg min(-1) (P<0.05). CONCLUSIONS: Our study demonstrates that even low
      doses of the polygelines Haemaccel and Gelofusine profoundly attenuate the
      tubular reabsorption of the low-molecular weight protein beta2-m. Atrial
      natriuretic peptide does not affect tubular protein reabsorption. Therefore, the
      rise in albuminuria during ANP infusion most likely reflects alterations in
      glomerular permeability.

PMID- 14636300
TI  - COX-2 inhibition and prostaglandin receptors in experimental nephritis.
AB  - BACKGROUND: Renal cyclooxygenases (COX) produce the prostaglandins (PG) E2, I2
      and thromboxane (TxA2), which interact with distinct G protein-coupled receptors.
      We investigated the expression of the three EP receptors EP2, EP3 and EP4 and the
      receptors for PGI2 (IP) and TxA2 (TP) in rats with passive Heymann nephritis
      (PHN). We studied their regulation by COX-2 inhibition with celecoxib. MATERIALS
      AND METHODS: Four groups of Wistar rats were studied: healthy rats (group A),
      healthy rats treated with celecoxib (group B), rats with PHN (group C), and rats
      with PHN receiving celecoxib (group D). Expression of the mRNA for all receptors
      in the renal cortex and for the EP3 receptor in cultured mesangial cells (MCs)
      was determined by semiquantitative reverse transcriptase polymerase chain
      reaction. Stable prostaglandin metabolites were measured in the urine by
      radioimmunoassay. RESULTS: Rats with PHN (group C) showed an 1.8-fold increase of
      cortical EP3 receptor mRNA expression as compared with controls (group A). In
      celecoxib-treated PHN rats (group D) the mRNA expression of the EP3 and EP4
      receptors was significantly reduced to 1.0-fold and 0.7-fold induction,
      respectively. Furthermore, the excretion of bicyclo-prostaglandin E2 (PGE2) was
      inhibited by celecoxib. No changes were observed in the expression of the other
      PG-receptors. In cultured MC, PGE2 enhanced the EP3 mRNA expression. CONCLUSIONS:
      These data suggest a predominant role of the EP3 receptor in the transduction of
      PGE2-actions in PHN. It was concluded that COX-2-dependent PGE2 is able to
      potentiate its effects in the kidney by up-regulating its own receptors.

PMID- 14636301
TI  - Synthesis and absorption markers of cholesterol in serum and lipoproteins during
      a large dose of statin treatment.
AB  - BACKGROUND: Serum contains noncholesterol sterols, which are reliable markers of
      cholesterol metabolism, but their presence and importance in different
      lipoproteins have been insufficiently studied. MATERIALS AND METHODS: Serum and
      lipoprotein cholesterol precursors squalene, cholestanol, desmosterol and
      lathosterol (markers of cholesterol synthesis) and cholestanol and plant sterols
      (markers of cholesterol absorption), and absorption efficacy and absolute
      synthesis of cholesterol were studied at baseline and during 6-month atorvastatin
      (80 mg day(-1)) treatment by the sterol balance technique in men with type 2
      diabetes. RESULTS: At baseline, approximately 14% of serum squalene was
      transported by VLDL, 12% by IDL, 40% by LDL and 30% by HDL. The respective values
      for the noncholesterol sterols were approximately 8, 4, 61 and 26%. The squalene
      to cholesterol ratios were highest in VLDL and IDL, those of cholestanol,
      desmosterol and absorption marker sterols were gradually higher, and that of
      lathosterol lower from VLDL to HDL. Atorvastatin reduced LDL cholesterol by
      approximately 50%, decreased the absolute cholesterol synthesis and turnover by
      approximately 40%, but increased significantly the fractional and mass absorption
      of cholesterol. In accordance with the fecal data, the ratios of the precursor
      sterols to cholesterol were reduced (-50%), but those of squalene (+48%) and the
      absorption sterols increased (e.g. 2.6-fold for sitosterol) similarly in each
      lipoprotein, but progressively from VLDL to HDL. CONCLUSIONS: Effective lowering
      of LDL cholesterol by large dose of statin is associated with decreased synthesis
      and turnover of cholesterol and increased fractional and mass absorption of
      cholesterol. These changes are detectable by noncholesterol sterols in serum and
      in different lipoprotein fractions.

PMID- 14636302
TI  - Increased skeletal muscle expression of PKC-theta but not PKC-alpha mRNA in type
      2 diabetes: inverse relationship with in-vivo insulin sensitivity.
AB  - BACKGROUND: Increases in PKC-theta (the major isoenzymic form of PKC in skeletal
      muscle) protein and isozyme activity have been reported in skeletal muscle from
      patients with type 2 diabetes mellitus (T2DM) and dietary-induced rodent models
      of insulin resistance, but the underlying biochemical mechanism is unclear and
      muscle PKC-theta mRNA expression has not been previously reported in patients
      with T2DM or in relation to in-vivo measurements of insulin sensitivity. METHODS:
      Diet-only treated patients with T2DM (n=7) and healthy nondiabetic controls (n=7)
      of similar BMI attended the clinical research unit on two occasions, 1 week
      apart, for a skeletal muscle biopsy 2 h after a 75-g oral glucose load and
      measurement of whole-body insulin sensitivity using the euglycaemic
      hyperinsulinaemic clamp. RESULTS: Type 2 DM patients were insulin resistant (M
      value 3.0 +/- 0.4 vs. 8.6 +/- 0.8 mg glucose kg(-1) min(-1)) with fasting
      hyperinsulinaemia (306 +/- 116 vs. 34 +/- 9 pmol L(-1), P<0.001) and
      hypertriglyceridaemia (3.6 +/- 0.7 vs. 1.3 +/- 0.3 mmol L(-1), P<0.01) relative
      to controls. Semi-quantitative RT-PCR showed that expression of PKC-theta mRNA
      (relative to GAPDH mRNA) was 6-fold higher in T2DM subjects (0.63 + 0.25% vs.
      0.09 + 0.07%, P<0.001), whereas there was no difference in expression of PKC
      alpha mRNA between the two groups. Expression of PKC-theta mRNA was inversely
      correlated with insulin sensitivity (M) and positively correlated with fasting
      serum insulin concentration (P<0.02). CONCLUSIONS: This is the first clinical
      study of PKC-theta mRNA expression in human diabetic skeletal muscle. The results
      indicate that transcriptional up-regulation of PKC-theta may at least partly
      contribute to the increased muscle PKC-theta signalling in T2DM, and that PKC
      theta mRNA may be inversely related to in-vivo insulin sensitivity.

PMID- 14636303
TI  - New concepts in bilirubin encephalopathy.
AB  - Revised concepts of bilirubin encephalopathy have been revealed by studies of
      bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats.
      Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated
      bilirubin (Bf), of which the dominant species at physiological pH is the
      protonated diacid, which can passively diffuse across cell membranes. As the
      binding affinity of plasma albumin for bilirubin decreases strikingly as albumin
      concentration increases, previously reported Bf values were underestimated. Newer
      diagnostic tests can detect reversible neurotoxicity before permanent damage
      occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at
      Bf only modestly above aqueous saturation and affects astrocytes and neurons,
      causing mitochondrial damage, resulting in impaired energy metabolism and
      apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and
      hampers transport of neurotransmitters. The concentrations of unbound bilirubin
      in the cerebro-spinal fluid and CNS cells are probably limited mainly by active
      export of bilirubin back into plasma, mediated by ABC transporters present in the
      brain capillary endothelium and choroid plexus epithelium. Intracellular
      bilirubin levels may be diminished also by oxidation, conjugation and binding to
      cytosolic proteins. These new concepts may explain the varied susceptibility of
      neonates to develop encephalopathy at any given plasma bilirubin level and the
      selective distribution of CNS lesions in bilirubin encephalopathy. They also can
      suggest better strategies for predicting, preventing and treating this syndrome.

PMID- 14636304
TI  - Four peptides decrease the number of human pancreatic adenocarcinoma cells.
AB  - BACKGROUND: Long-acting natriuretic peptide, vessel dilator, kaliuretic peptide
      and atrial natriuretic peptide are four peptide hormones synthesized by the same
      gene. Their main known biologic properties are sodium and water excretion and
      blood pressure lowering in both animals and humans. METHODS AND MATERIALS: These
      four peptide hormones, each at their 1-microm concentrations, were evaluated for
      their ability to decrease the number and/or proliferation of human pancreatic
      adenocarcinoma cells in culture at 24, 48, 72 and 96 h. RESULTS: Vessel dilator,
      long-acting natriuretic peptide, kaliuretic peptide and atrial natriuretic
      peptide decreased the number of human pancreatic adenocarcinoma cells in culture
      by 65% (P<0.001), 47% (P<0.01), 37% (P<0.05) and 34% (P<0.05), respectively,
      within 24 h. This decrease was sustained without any proliferation of the cancer
      cells occurring in the 3 days following this decrease in number. The mechanism of
      these peptide hormones' decrease in cancer cell number and antiproliferative
      effects was a 83% (P<0.001) or greater inhibition of DNA synthesis but not owing
      to enhanced apoptosis, i.e. programmed cell death. The two known mediators of
      these peptide hormones' mechanism(s) of action, i.e. cyclic GMP and prostaglandin
      E2, inhibited DNA synthesis in these adenocarcinoma cells by 51% and 23%,
      respectively. CONCLUSIONS: Four peptide hormones significantly decrease the
      number of pancreatic adenocarcinoma cells within 24 h and inhibit the
      proliferation of these cells for at least 96 h. Their mechanism of doing so is
      via inhibition of DNA synthesis mediated in part by cyclic GMP.

PMID- 14636305
TI  - Acute haemodynamic effects of losartan in anaesthetized cirrhotic rats.
AB  - BACKGROUND: Portal hypertension in cirrhosis is the result of increased
      intrahepatic vascular resistance to portal outflow as well as increased portal
      tributary blood flow. The angiotensin II type 1 receptor antagonist losartan has
      been suggested as a portal pressure-lowering drug in patients with cirrhosis.
      AIM: To investigate the systemic and splanchnic haemodynamic effects of different
      doses of losartan. METHODS: In 35 anaesthetized rats with secondary biliary
      cirrhosis, 3, 10 or 30 mg of losartan kg(-1) or solvent were administered
      intravenously. Ten sham-operated rats served as controls. Mean arterial pressure
      and portal pressure were measured by catheters in the femoral artery or portal
      vein. Systemic and splanchnic haemodynamics and mesenterico-systemic shunt rate
      were determined by the coloured microsphere method. RESULTS: Losartan reduced
      portal pressure (sham: 9.1 +/- 0.4. cirrhosis: 19.3 +/- 1.1, after 3 mg kg(-1) of
      losartan 16.4 +/- 0.4, after 10 mg kg(-1) of losartan 15.6 +/- 0.6, after 30 mg
      kg(-1) of losartan 14.9 +/- 0.6 mmHg) without reducing portal sinusoidal
      resistance. However, in cirrhotic rats it reduced portal tributary blood flow
      (sham: 4.3 +/- 0.6. cirrhosis: 8.6 +/- 1.4, after 3 mg kg(-1) of losartan 3.8 +/-
      0.7, after 10 mg kg(-1) of losartan 4.7 +/- 0.5, after 30 mg kg(-1) of losartan
      5.9 +/- 0.9 mmHg). This was owing either to an increase in splanchnic vascular
      resistance at the 3 mg kg(-1) dose or to a reduction in the splanchnic perfusion
      pressure gradient secondary to a reduction in mean arterial pressure at the 10
      and 30 mg kg(-1) doses (mean arterial pressure: sham: 109.7 +/- 4.8. cirrhosis:
      109.4 +/- 2.8, after 3 mg kg(-1) of losartan 99.7 +/- 2.9, after 10 mg kg(-1) of
      losartan 89.9 +/- 3.4, after 30 mg kg(-1) of losartan 81.0 +/- 2.9 mmHg).
      CONCLUSIONS: Low doses of losartan reduce portal hypertension by an increase in
      splanchnic vascular resistance without hypotensive side-effects on arterial
      pressure.

PMID- 14636306
TI  - Inhibition of intracellular tumour necrosis factor (TNF)-alpha and interleukin
      (IL)-6 production in human monocytes by iloprost.
AB  - BACKGROUND: To investigate the effects of iloprost as a stable prostacyclin
      analogue on intracellular expression of IL-6 and TNF-alpha of lipopolysaccharide
      (LPS)-stimulated human monocytes in a whole blood system assessed by flow
      cytometry. MATERIAL AND METHODS: Whole blood of six healthy volunteers processed
      immediately after withdrawal and twice on different days (six measurements per
      experiment) was stimulated in two different settings with LPS (final
      concentrations 0.2 ng mL(-1) and 10 ng mL(-1)) and incubated with iloprost (final
      concentrations in each experiment were 0.01 nm, 0.1 nm, 0.3 nm, 1 nm, 3 nm, 10
      nm, 30 nm and 100 nm) for 3 h at 37 degrees C and 5% CO2. Intracellular
      expression of IL-6 and TNF-alpha was assessed by flow cytometry. RESULTS: Our
      investigations showed, for the first time, that iloprost (0.1 nm up to 100 nm)
      caused a dose-dependent inhibitory effect of IL-6 production in human monocytes
      stimulated with LPS (10 ng mL(-1)), which was even more obvious in monocytes
      stimulated with lower concentrated LPS (0.2 ng mL(-1)). Iloprost (0.1 nm up to
      100 nm) was found to inhibit TNF-alpha production of LPS-stimulated monocytes in
      a dose-dependent fashion not influenced by LPS concentration. CONCLUSIONS: Apart
      from the vasodilatory and antithrombotic effects, iloprost may also down-regulate
      the intracellular expression of IL-6 and TNF-alpha in human monocytes.

PMID- 14636307
TI  - Lack of relevant association between prolactin and immune responses in patients
      with chronic heart failure.

PMID- 14636309
TI  - Soluble interleukin-2 receptor: is there a role in ischaemic cardiomyopathy?

PMID- 14636311
TI  - Validation of the oral glucose insulin sensitivity index to assess insulin
      sensitivity in Japanese subjects for use in clinical practice.

PMID- 14636312
TI  - Selective induction of total and allergen-specific IgE production by passive
      smoking.

PMID- 14636313
TI  - Atrial natriuretic peptide and albuminuria in diabetic patients.

PMID- 14636315
TI  - Therapy discovery for pharmacoresistant epilepsy and for disease-modifying
      therapeutics: summary of the NIH/NINDS/AES models II workshop.

PMID- 14636316
TI  - Brain access and anticonvulsant efficacy of carbamazepine, lamotrigine, and
      felbamate in ABCC2/MRP2-deficient TR- rats.
AB  - PURPOSE: Different adenosine triphosphate (ATP)-driven multidrug transporters
      have been described to be expressed in the luminal membrane of blood-brain
      barrier (BBB) endothelial cells. At this site, multidrug transporters have been
      suggested to restrict penetration of drugs into the brain. Increasing evidence
      suggests that overexpression of different multidrug transporters occurs in the
      region of the epileptic focus of pharmacoresistant epilepsy patients. Based on
      the assumption that antiepileptic drugs (AEDs) are substrates of these
      transporters, this overexpression may limit access of AEDs to epileptic neurons
      and may contribute to drug-refractoriness. In a recent study, overexpression of
      multidrug resistance protein 2 (ABCC2; MRP2) was reported in BBB endothelial
      cells of epileptic focal tissue from pharmacoresistant patients. With brain
      microdialysis, we recently demonstrated that the AED phenytoin is subject to
      transport by ABCC2 at the BBB, whereas phenobarbital does not seem to be a
      substrate of ABCC2. METHODS: We investigated whether ABCC2 is functionally
      involved in transport of the AEDs carbamazepine (CBZ), lamotrigine (LTG), and
      felbamate (FBM) across the BBB. The distribution of these AEDs into the brain of
      ABCC2-deficient TR- rats was determined. RESULTS: AED concentrations in plasma
      and brain extracellular space of these mutant rats did not differ significantly
      from those of rats of the corresponding background strain. In the amygdala
      kindling model of epilepsy, the anticonvulsant efficacy of LTG and FBM was
      comparable in both groups of rats. In contrast, CBZ exhibited a higher
      anticonvulsant activity in kindled ABCC2-deficient rats as compared with
      nonmutant rats. CONCLUSIONS: In this present study, the microdialysis results
      gave no evidence that ABCC2 function modulates entry of CBZ, LTG, and FBM into
      the CNS of naive rats. However, ABCC2 deficiency was associated with an increased
      anticonvulsant response of CBZ in the kindling model. Future investigations are
      planned to identify the underlying mechanism for this difference, clarifying
      whether a pharmacokinetic difference is detectable only when brain access of CBZ
      is compared in kindled ABCC2-deficient rats and kindled nonmutant rats, which may
      have an increased expression of ABCC2 in response to seizures. The data
      substantiate that ABCC2-deficient TR- rats are a useful tool for defining the
      role of ABCC2 for transport of AEDs, and give evidence that the use of kindled TR
      rats may provide important supplementary information.

PMID- 14636317
TI  - Unidirectional cross-tolerance from levetiracetam to carbamazepine in amygdala
      kindled seizures.
AB  - PURPOSE: Tolerance is a potential problem in long-term anticonvulsant therapy of
      epilepsy, bipolar disorder, and neuropathic pain. The present study was designed
      to determine whether cross-tolerance occurs between levetiracetam (LEV) and
      carbamazepine (CBZ) in amygdala-kindled rats. METHODS: Male Sprague-Dawley rats
      were implanted with an electrode into the left amygdala. While kindling
      stimulation was started, animals received repeated treatment (i.p.) with saline
      (n = 7) or LEV (150 mg/kg, n = 8). Saline-injected rats were subsequently
      challenged with a single dose of 150 mg/kg LEV when full kindling developed
      (stage > or =4). Both groups of rats were then administered long-term CBZ (5
      mg/kg) until rats developed complete tolerance. All CBZ-tolerant rats were
      subsequently re-exposed to LEV (150 mg/kg) for an additional 10 consecutive days.
      RESULTS: Repeated LEV treatment significantly suppressed the increase in seizure
      stage, seizure duration, and afterdischarge duration induced by amygdala
      stimulation, markedly increasing the number of stimulations to achieve a kindling
      major motor seizure. The LEV challenge produced a more robust suppression of
      seizure stage in saline-injected rats compared with LEV-treated animals. CBZ
      treatment markedly suppressed fully kindled seizures in rats initially injected
      with saline, and then anticonvulsant tolerance rapidly developed after 3-4 days
      of repeated treatment. In contrast, rats that had initially received repeated LEV
      treatment did not show a response to treatment with CBZ (5 mg/kg). When CBZ
      tolerant rats were subsequently exposed to LEV (150 mg/kg), noticeable
      anticonvulsant effects were observed; but these were gradually lost with
      increasing numbers of LEV exposures. CONCLUSIONS: Whereas LEV shows potent
      antiepileptogenic and anticonvulsant effects in amygdala-kindled rats, its
      repeated treatment induces anticonvulsant tolerance and unidirectional cross
      tolerance to CBZ. In contrast, anticonvulsant tolerance to CBZ does not transfer
      to LEV. The mechanistic implications of the present results for clinical
      therapeutics remain to be evaluated.

PMID- 14636318
TI  - The anticonvulsant effects of progesterone and 5alpha-dihydroprogesterone on
      amygdala-kindled seizures in rats.
AB  - PURPOSE: Progesterone has been shown to be anticonvulsant in several animal
      seizure models. The purpose of the present study was to investigate the
      anticonvulsant actions of progesterone and its primary metabolite 5alpha
      dihydroprogesterone in the amygdala kindling model. METHODS: Female Wistar rats
      were implanted in the right basolateral amygdala with a long-term, bipolar
      electrode. The subjects were kindled to 30 stage 5 seizures and stability tested.
      Multiple doses of progesterone and 5alpha-dihydroprogesterone were then tested
      for anticonvulsant activity against focal electrographic and generalized
      convulsive kindled seizures. The time course of progesterone's anticonvulsant
      action also was examined. RESULTS: Progesterone had a median effective dose
      (ED50) of 103 mg/kg against generalized convulsions at 15 min after injection.
      Subjects were not sedated at the time of seizure testing, although sedation
      developed later (40-60 min after injection). In time-course experiments, it was
      found that 120 mg/kg of progesterone caused complete suppression of the
      generalized convulsion from 20 to 160 min after injection. Suppression of the
      focal discharge also was seen in some animals between 20 and 160 min. 5alpha
      dihydroprogesterone had an ED50 of 2.9 mg/kg against generalized kindled
      convulsions and an ED50 of 4.3 mg/kg against focal afterdischarge 15 min after
      injection. 5alpha-dihydroprogesterone did not produce sedation 15 min after
      injection, or at any later time interval. CONCLUSIONS: Progesterone is
      anticonvulsant only at high doses when tested against amygdala kindled seizures.
      5alpha-dihydroprogesterone is considerably more potent than progesterone. At low,
      nonsedative doses, it was effective against both the kindled amygdala focal
      afterdischarge and the generalized convulsion.

PMID- 14636319
TI  - Long-lasting anticonvulsant effect of focal cooling on experimental neocortical
      seizures.
AB  - PURPOSE: Previous clinical and experimental observations have demonstrated that
      cooling the brain can rapidly terminate focal seizures. We wished to determine
      whether cooling at regular intervals could prevent or attenuate the development
      of seizures in a model of focal epilepsy. METHODS: We induced focal neocortical
      seizures in halothane-anesthetized rats by the microinjection of 4-aminopyridine
      (4-AP) into the motor cortex. With a small thermoelectric device, the site of the
      4-AP injection was either cooled intermittently (PostCool) for 30 s every 2 min,
      starting 15 min after the 4-AP injection, or precooled (PreCool) for 30 min
      before 4-AP injection, by using the same 30-s cooling cycle. Seizures were
      quantified in 30-min observation periods for 1.5 h. RESULTS: The average
      durations of PostCool and PreCool seizures were shorter than those of controls (p
      < 0.001). In addition, total seizure duration was significantly reduced in both
      groups, compared with controls (p < 0.01). The ratio of the root mean square
      power during a seizure to power in the immediate preseizure period was reduced in
      both PostCool and PreCool groups (p < 0.001). The number of seizures
      significantly declined over a 30- to 60-min period in both experimental groups,
      and by 60 min, no seizures were evident. CONCLUSIONS: These experiments show that
      gentle cooling to 20 degrees C is capable of markedly reducing subsequent seizure
      frequency and intensity. The effects in our model, which generates very frequent
      and intense ictal activity, were robust, suggesting that prophylactic cooling
      might be even more beneficial in clinical situations. The physiologic mechanism
      for this preventive effect requires elucidation.

PMID- 14636320
TI  - Hyperexcitability of CA3 pyramidal cells in mice lacking the potassium channel
      subunit Kv1.1.
AB  - PURPOSE: To investigate further the membrane properties and postsynaptic
      potentials of the CA3 pyramidal cells in mice that display spontaneous seizures
      because of a targeted deletion of the Kcna1 potassium channel gene (encoding the
      Kv1.1 protein subunit). METHODS: Intracellular recordings were obtained from CA3
      pyramidal cells in hippocampal slices prepared from Kcna1-null and control
      littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating
      mossy fibers; antidromically, by activating Schaffer collaterals; and by
      injecting intracellular pulses of current. Responses evoked under these
      conditions were compared in both genotypes in normal extracellular medium
      (containing 3 mM potassium) and in medium containing 6 mM potassium. RESULTS:
      Recordings from CA3 pyramidal cells in Kcna1-null and littermate control slices
      showed similar membrane and action-potential properties. However, in 33% of cells
      studied in Kcna1-null slices bathed in normal extracellular medium, orthodromic
      stimulation evoked synaptically driven bursts of action potentials that followed
      a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP)
      sequence. Such bursts were not seen in cells from control slices. The short
      latency gamma-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in
      null and control slices. When extracellular potassium was elevated and excitatory
      synaptic transmission was blocked, antidromic activation or short pulses of
      intracellular depolarizing current evoked voltage-dependent bursts of action
      potentials in the majority of cells recorded in Kcna1 null slices, but only
      single spikes in control slices. CONCLUSIONS: Lack of Kv1.1 potassium channel
      subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected
      in the propensity of these cells to generate multiple action potentials. The
      action-potential burst did not appear to result from loss of GABAA receptor
      mediated inhibition. This property of CA3 neurons, seen particularly when tissue
      conditions become abnormal (e.g., elevated extracellular potassium), helps to
      explain the high seizure susceptibility of Kcna1-null mice.

PMID- 14636321
TI  - Single-unit analysis of substantia nigra pars reticulata neurons in freely
      behaving rats with genetic absence epilepsy.
AB  - PURPOSE: The substantia nigra pars reticulata (SNpr) is assumed to be involved in
      the control of several kinds of epileptic seizures, an assumption based mostly on
      neuropharmacologic evidence. However, only very few neurophysiological recordings
      from the basal ganglia support neuropharmacologic data. We investigated the
      electrophysiologic activity of SNpr neurons in rats with genetic absence
      epilepsy. METHODS: Electrocorticography (ECoG) and multi-unit recordings using
      permanently implanted tetrodes were obtained in freely behaving rats. After spike
      sorting, auto- and cross-correlation analysis was used to detect oscillatory
      neuronal activities and synchronizations. RESULTS: During interictal periods,
      neither oscillation nor synchronization could be observed in the firing patterns
      of SNpr neurons. At the beginning of the absence seizure, the firing rate
      increased significantly. The SNpr neurons started firing in bursts of action
      potentials. Bursts were highly correlated to the spike-and-wave discharges (SWDs)
      in the ECoG, mainly after the spike component of the cortical spike-and-wave
      complex. Moreover, pairs of SNpr neurons tended to fire synchronously. Before the
      end of the seizure, the firing rate decreased progressively, and the burst-firing
      pattern ended at or before the end of the SWDs. Once the SWDs had stopped, the
      SNpr neurons resumed their basal firing pattern as before the seizure onset.
      CONCLUSIONS: These results provide electrophysiologic evidence that firing
      patterns and synchronization of SNpr neurons are in phase with the occurrence of
      SWDs. The findings support the concept that nigral control mechanisms are
      involved in modulating the propagation of an ongoing generalized seizure.

PMID- 14636322
TI  - Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane
      X receptor by topiramate.
AB  - PURPOSE: In clinical studies, topiramate (TPM) was shown to cause a dose
      dependent increase in the clearance of ethinyl estradiol. We hypothesized that
      this interaction results from induction of hepatic cytochrome P450 (CYP) 3A4 by
      TPM. Accordingly, we investigated whether TPM induces CYP3A4 in primary human
      hepatocytes and activates the human pregnane X receptor (hPXR), a nuclear
      receptor that serves as a regulator of CYP3A4 transcription. METHODS: Human
      hepatocytes were treated for 72 h with TPM (10, 25, 50, 100, 250, and 500 microM)
      and known inducers, phenobarbital (PB; 2 mM), and rifampicin (10 microM). The
      rate of testosterone 6beta-hydroxylation by hepatocytes served as a marker for
      CYP3A4 activity. The CYP3A4-specific protein and mRNA levels were determined by
      using Western and Northern blot analyses, respectively. The hPXR activation was
      assessed with cell-based reporter gene assay. RESULTS: Compared with controls,
      TPM (50-500 microM)-treated hepatocytes exhibited a considerable increase in the
      CYP3A4 activity (1. 6- to 8.2-fold), protein levels (4.6- to 17.3-fold), and mRNA
      levels (1.9- to 13.3-fold). Comparatively, rifampicin (10 microM) effected 14.5-,
      25.3-, and a 20.3-fold increase in CYP3A4 activity, immunoreactive protein
      levels, and mRNA levels, respectively. TPM (50-500 microM) caused 1.3- to 3-fold
      activation of the hPXR, whereas rifampicin (10 microM) caused a 6-fold
      activation. CONCLUSIONS: The observed induction of CYP3A4 by TPM, especially at
      the higher concentrations, provides a potential mechanistic explanation of the
      reported increase in the ethinyl estradiol clearance by TPM. It also is
      suggestive of other potential interactions when high-dose TPM therapy is used.

PMID- 14636323
TI  - An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with
      generalized epilepsy, ichthyosis, and attention deficits.
AB  - PURPOSE: We describe two brothers with generalized epilepsy, attention deficits,
      congenital ichthyosis, and Leri-Weill dyschondrosteosis who harbor an unusual Xp;
      Yq translocation chromosome, resulting in a novel contiguous gene syndrome
      because of deletion of genes from the distal short arm of the X chromosome.
      METHODS: Physical examination, neuropsychologic testing, EEG, and neuroimaging
      studies were performed. Because of their unusual phenotype, karyotyping,
      fluorescence in situ hybridization, and further molecular analyses were carried
      out to refine the break points of the underlying unbalanced sex chromosome
      rearrangement. RESULTS: The subjects had generalized epilepsy, X-linked
      ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention
      deficits. The brothers' karyotype was unbalanced; they inherited a maternal
      derivative X chromosome. Deleted distal Xp genes included short-stature homeobox
      on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X
      chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype
      was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat.
      CONCLUSIONS: Loss of distal contiguous Xp genes resulted in a syndrome comprising
      bony deformities, ichthyosis, attention problems, and generalized epilepsy.
      Candidate epilepsy genes within the deleted segment, such as ASMT, a gene
      involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses
      should be included in the clinical evaluation of patients with generalized
      epilepsy and complex phenotypes.

PMID- 14636324
TI  - Diffusion tensor MRI and fiber tractography of cerebellar atrophy in phenytoin
      users.
AB  - PURPOSE: The usefulness of diffusion tensor magnetic resonance imaging (DT-MRI)
      is still in debate, and the development of clinically feasible scan protocol is
      encouraged. The purpose of this study was to investigate the afferent fiber
      system to the cerebellum in patients with phenytoin (PHT)-induced cerebellar
      atrophy in comparison with cerebellar atrophy of other etiologies by using DT
      MRI. METHODS: Thirteen patients (M/F ratio, 7:6; mean age, 42.5 years) and age
      matched normal controls (n = 8) participated in this study. The patient group
      consisted of epilepsy patients who had received PHT therapy (n = 9) and
      clinically diagnosed as having olivopontocerebellar atrophy (OPCA; n = 4). DT-MRI
      was performed by using diffusion weighting of b = 600 s/mm2, and fractional
      anisotropy (FA) and color-coded vector maps were generated. FA of the middle
      cerebellar peduncle (MCP), the cerebellum, and transverse pontine fibers (TPF)
      was measured and compared between PHT and OPCA patients. RESULTS: Normal subjects
      showed FA values of 0.81 +/- 0.07 in MCP, 0.69 +/- 0.04 in TPF, and PHT users
      showed FA values of 0.84 +/- 0.09 in MCP, 0.72 +/- 0.08 in TPF, and 0.21 +/- 0.04
      in cerebellum. OPCA patients showed FA values of 0.39 +/- 0.11 in MCP, 0.46 +/-
      0.12 in TPF, and 0.22 +/- 0.07 in cerebellum. PHT users showed a statistically
      significant reduction of FA only in cerebellum, whereas OPCA demonstrated
      significant decrease of FA in MCP, TPF, and cerebellum (one-way analysis of
      variance, p < 0.01). Three-dimensional reconstruction of fiber tracts
      demonstrated decreased volume and altered fiber integrity within the peduncles
      and transverse pontine fibers in the OPCA group, whereas fiber course patterns in
      PHT users were similar to those in controls. CONCLUSIONS: PHT users showed normal
      orientation and anisotropy of MCP and TPF, whereas OPCA demonstrated impaired
      values, suggesting that PHT directly affects the cerebellum. DT-MRI can
      demonstrate detailed fiber configurations in degenerative diseases of brainstem
      and cerebellum and provides insight into the pathomechanisms of cerebellar
      atrophy.

PMID- 14636325
TI  - Correlation between language organization and diffusion tensor abnormalities in
      refractory partial epilepsy.
AB  - PURPOSE: Atypical language organization is more frequently found in patients with
      refractory partial epilepsy than in healthy controls; however, the reasons for
      this are not well known. Here we assess the relation between language laterality
      index (LI) and white-matter tract changes. METHODS: Nine patients with refractory
      partial epilepsy were assessed with a 3-T GE scanner. Functional magnetic
      resonance imaging (fMRI) of language and diffusion tensor imaging (DTI) were
      acquired. For the fMRI, a noun-verb generation task was performed, all images
      were motion corrected, and activated pixels in classic language areas were
      counted. The DTI images were acquired in six standard directions with an initial
      non-diffusion-weighted scan. The "average anisotropy" was determined in a region
      of interest in the frontal lobe, temporal lobe, and parietal lobe white matter.
      An asymmetry index (AI) was calculated for language and DTI. Atypical language
      lateralization was diagnosed if the lateralization index (LI)-language was
      smaller than 0.4. RESULTS: Two of the nine patients had atypical language
      localization (LI-language, -0.6, and 0.3); both had left temporal DTI asymmetry
      (LI-DTI, -0.3 and -0.2). The remaining seven patients had typical language
      localization, and no marked DTI abnormalities. Asymmetry in temporal lobe DTI
      correlated with LI-language (r= 0.8; p = 0.006). CONCLUSIONS: Atypical language
      lateralization in patients with partial epilepsy may be associated with white
      matter tract abnormalities.

PMID- 14636326
TI  - Texture analysis of hippocampal sclerosis.
AB  - Mesial temporal lobe epilepsy (MTLE) is frequently associated with refractory
      seizures and pathologic features of hippocampal sclerosis (HS). Quantitative
      magnetic resonance imaging (MRI) techniques can improve the detection and
      quantification of HS. The objective of this study was to evaluate whether MRI
      texture analysis can detect hippocampal abnormalities in patients with
      pathologically proven HS. METHODS: Nineteen consecutive patients who underwent
      surgery for refractory unilateral MTLE and had HS diagnosed on histopathology (12
      right and seven left) had their preoperative MRIs evaluated. We performed texture
      analysis in 3-mm coronal T1-IR MRIs, focusing on the hippocampal head, by using
      the software MAZDA. Data were compared with those of a group of 78 normal
      hippocampi from 39 healthy adult volunteers through multivariate analysis of
      variance and selection of the most significant texture parameters. RESULTS:
      Overall, almost all parameters of texture could discriminate the group of
      hippocampi with HS and the group of contralateral hippocampi from the group of
      normal hippocampi, but the post hoc comparison showed no differences between HS
      and contralateral hippocampi. CONCLUSIONS: These results provide evidence of
      texture alteration in MRIs of hippocampi with HS and corroborate the hypothesis
      of bilaterality of hippocampal damage in patients with MTLE, but further studies
      are needed to investigate the lateralization power of texture analysis.

PMID- 14636327
TI  - Gender-specific differences of hypometabolism in mTLE: implication for cognitive
      impairments.
AB  - PURPOSE: To determine gender differences of hypometabolism and their implications
      for cognitive impairment in patients with medically refractory mesial temporal
      lobe epilepsy (mTLE). METHODS: Regional cerebral glucose metabolism (rCMRGlu) was
      studied in 42 patients (21 male, 21 female) with either left- or right-sided mTLE
      (22 left, 20 right) and in 12 gender- and age-matched healthy controls during
      resting wakefulness and in 12 sex- and age-matched healthy controls. Clinical
      characteristics were balanced across the patient subgroups. All patients were
      subjected to neuropsychological assessment: 41 patients had histologic changes of
      definite or probable hippocampal sclerosis. RESULTS: Data analysis based on pixel
      by-pixel comparisons and on a laterality index of regions of interest (ROIs)
      showed significant depressions of the mean rCMRGlu extending beyond the
      mesiotemporal region and temporolateral cortex to extratemporal regions including
      the frontoorbital and insular cortex in mTLE patients. Extramesiotemporal
      hypometabolism prevailed in the male patients. Metabolic asymmetry in temporal
      and frontal regions was related to performance in the Trail-Making Test and WAIS
      R subitems. CONCLUSIONS: Our data showed a gender-specific predominance of
      extramesiotemporal hypometabolism in male patients with mTLE related to
      abnormalities of temporal and frontal lobe functions.

PMID- 14636328
TI  - The significance of ear plugging in localization-related epilepsy.
AB  - PURPOSE: The localizing value of ear plugging in the treatment of auditory onset
      partial seizures, to our knowledge, has not been previously described. We propose
      that ear plugging is a clinical response to a sensory seizure manifested as an
      auditory hallucination and a tool for identifying the seizure focus in the
      auditory cortex on the superior temporal gyrus. METHODS: We report on three
      children who had prior epilepsy surgery for recurrent symptomatic localization
      related epilepsy and who, subsequent to their surgery, displayed stereotyped
      unilateral or bilateral ear plugging at the onset of partial seizures. We studied
      scalp video electroencephalography (VEEG), magnetoencephalography (MEG), and
      magnetic resonance imaging (MRI) in all three. Additionally, we used
      electrocorticography (ECoG) in two patients, intracranial VEEG monitoring in one
      patient, and functional MRI language mapping in two patients. RESULTS: All three
      patients plugged their ears with their hands during auditory auras that localized
      to the superior temporal gyrus and were followed by partial seizures that spread
      to a wider field, as shown on scalp and intracranial VEEG. All three patients had
      MEG interictal discharges in the superior temporal gyrus. One patient who was
      nonverbal and unable to describe an auditory phenomenon plugged the ear
      contralateral to where temporal lobe-onset seizures and MEG interictal discharges
      occurred. CONCLUSIONS; Ear-plugging seizures indicate an auditory aura and may
      also lateralize seizure onset to the contralateral temporal lobe auditory cortex.
      Stereotyped behaviors accompanied by epileptic seizures in children who have poor
      communication skills are important in the seizure semiology of localization
      related epilepsy.

PMID- 14636329
TI  - Long-term outcome of nonsurgical candidates with medically refractory
      localization-related epilepsy.
AB  - PURPOSE: Epilepsy surgery can result in complete seizure remission rates of upto
      80% in patients with mesial temporal sclerosis and unilateral seizures. The
      seizure-free rate after surgery for patients with extratemporal nonlesional
      epilepsy has ranged between 30% and 40%. Some patients with medically refractory
      localization-related epilepsy cannot be offered surgical resection because of
      inadequate localization of the epileptogenic zone, documentation of bilateral
      ictal onsets, or functionally important areas of cortex that prohibit resection.
      The short-term rate of complete remission with medications in temporal lobe
      epilepsy is poor. Less is known about remission rates in patients who are not
      surgical candidates. In this study, we evaluated the outcome of medical treatment
      in patients with medically refractory partial epilepsy who were evaluated for
      possible epilepsy surgery but deemed to be inadequate surgical candidates.
      METHODS: A retrospective chart review and telephone survey with a self-rating
      questionnaire were completed for all patients who underwent epilepsy surgery
      evaluation but were not ultimately offered surgical treatment at the University
      of Michigan from 1990 through 1998. We assessed changes in seizure frequency and
      type, imaging characteristics, ictal recordings, interim medication history, and
      subjective changes in quality of life. RESULTS: Thirty-four subjects were
      available for follow-up study, at an average of >4 years after surgical
      evaluation. A significant reduction in seizure frequency was noted at the time of
      follow-up compared with that at the time of surgical evaluation. Of patients, 21%
      achieved seizure remission and remained seizure free for an average of 2.5 years.
      Four of the seven seizure-free patients attributed their remission to new
      antiepileptic drugs (AEDs). On a global self-rating item, 15 of 34, or 44%, felt
      more or much more satisfied with their lives, and 41% felt their quality of life
      was stable. CONCLUSIONS: A surprisingly large number of patients we surveyed,
      with refractory partial epilepsy not eligible for surgical management, reported
      reduced seizure frequency at follow-up, and 21% were seizure free. Our findings
      suggest that the long-term prognosis in patients with refractory partial epilepsy
      who are not surgical candidates may be more positive than might be generally
      expected.

PMID- 14636330
TI  - The role of hippocampal sclerosis in topiramate-related depression and cognitive
      deficits in people with epilepsy.
AB  - PURPOSE: To clarify the role of hippocampal sclerosis (HS) in developing
      psychiatric and cognitive adverse events during therapy with topiramate (TPM) in
      patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the data of 70
      patients with TLE and HS and 128 patients with cryptogenic TLE matched for age,
      sex, starting dose, and titration schedule of TPM. They were selected from the
      first consecutive 431 patients started on TPM between 1995 and 1999. RESULTS:
      Patients with HS were more likely to develop cognitive adverse events (CAEs; p =
      0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p =
      0.007). However, regression analysis demonstrated that only HS was a predictive
      factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3;
      p = 0.02). CONCLUSIONS: Patients with TLE and HS were more prone to develop CAEs
      and depression than were patients with cryptogenic TLE, during TPM therapy,
      despite the same titration schedule. The presence of HS and not duration of
      epilepsy or polytherapy regimen represented the main risk factor.

PMID- 14636331
TI  - The influence of comorbid depression on seizure severity.
AB  - PURPOSE: To determine the relation between depressive symptoms and seizure
      severity among people with epilepsy. METHODS: A postal questionnaire was used to
      survey a nationwide community sample about seizures and depression. The Seizure
      Severity Questionnaire (SSQ) assessed the severity and bothersomeness of seizure
      components. The Centers for Epidemiological Studies-Depression scale categorized
      levels of depression. RESULTS: Respondents categorized as having current severe
      (SEV, n = 166), mild-moderate (MOD, n = 74), or no depression (NO, n = 443)
      differed significantly in SSQ scores (all p < 0.0001). People with SEV or MOD
      reported significantly worse problems than did those with NO depression for
      overall seizure recovery (mean, 5.3, 4.9, 4.5, respectively); overall severity
      (5.0, 4.5, 4.2); and overall seizure bother (5.3, 4.8, 4.4) (all p < 0.005).
      Cognitive, emotional, and physical aspects of seizure recovery also were rated
      worse among people with SEV than with NO depression (all p < 0.05). Symptoms of
      depression were significantly correlated with higher levels of all components of
      generalized tonic-clonic seizure severity (r = 0.33-0.48; all p < 0.0001), and
      partial seizures (r = 0.31-0.38; all p < 0.01). CONCLUSIONS: Clinically depressed
      people with epilepsy reported higher levels of perceived severity and bother from
      seizures, as well as greater problems with overall seizure recovery than did
      nondepressed people experiencing similar types of seizures. The pervasive
      influence of depressive symptoms on reports of seizure activity suggests that
      people with epilepsy should be screened for depression. These data highlight the
      importance of detecting and treating depression among people with epilepsy.

PMID- 14636332
TI  - Levetiracetam and partial seizure subtypes: pooled data from three randomized,
      placebo-controlled trials.
AB  - PURPOSE: To determine the effect of levetiracetam (LEV) on partial seizure
      subtypes (simple partial, complex partial, and secondarily generalized seizures)
      in patients with refractory epilepsy. METHODS: Pooled results from three placebo
      controlled trials were analyzed. RESULTS: A statistically significant reduction
      in the frequency of all partial seizures and all seizure subtypes was observed in
      the LEV group (p < 0.001 vs. placebo). The proportion of patients in whom
      secondarily generalized seizures could be prevented over and above the reduction
      of partial seizures was significantly greater in the LEV group as compared with
      placebo, with an odds ratio of 1.83 [95% confidence interval (CI), 1.10-3.05].
      CONCLUSIONS; LEV reduces frequency of simple and complex partial seizures. In
      addition, it demonstrates a specific, independent reduction of secondarily
      generalized seizures.

PMID- 14636333
TI  - Vagal nerve stimulation induces intermittent hypocapnia.
AB  - PURPOSE: To study whether respiratory alteration caused by vagal nerve
      stimulation (VNS) can change end-tidal carbon dioxide (EtCO2) levels. METHODS: We
      performed polygraphic recordings including capnographic monitoring during daytime
      sleep on adults with VNS therapy. RESULTS: Ten of 13 patients showed VNS-induced
      alterations in the frequency or amplitude of respiration. Five patients had a
      consistent increase in respiratory rate with a simultaneous, consistent and
      significant decrease (p < 0.01; 5-22%) in EtCO2 during VNS. Three subjects showed
      occasional decreases in EtCO2 during VNS, and two showed no clearly detectable
      VNS-related EtCO2 changes. CONCLUSIONS: Our findings suggest that VNS may alter
      brain CO2 levels through changes in respiration. Because carbon dioxide (CO2) has
      potent effects on various brain functions, it is possible that these transient
      CO2 changes may have an effect on the state transitions between interictal and
      preictal states.

PMID- 14636334
TI  - Infantile spasms in remission may reemerge as intractable epileptic spasms.
AB  - BACKGROUND: West syndrome consists of infantile spasms with hypsarrhythmia and is
      perceived as a disorder of infants. METHODS: We describe 10 patients with West
      syndrome with spasms that remitted, started again, and persisted (followed up for
      8-25 years). RESULTS: In all, West syndrome developed at younger than 17 months
      (five cryptogenic, six symptomatic). With initial treatment, spasms completely
      stopped for 4.5 months to 6 years, when epileptic spasms returned. Recurrent
      spasms were typical with brief arm extension, eye elevation, and head drop
      without falling. Spasms lasted 2-6 s in rhythmic strings over 20- to 60-min
      periods and occurred daily throughout follow-up. Persistent spasms were
      particularly troublesome, because of incontinence in one and postictal confusion
      in several. During the string of spasms, most refused to interact, and several
      would wander off. Up to 15 antiepileptic drugs did not render any patient spasm
      free. Only two had persistent spasms as the only seizure type; six also had
      intractable complex partial seizures, and three had occasional grand mal
      convulsions. Interictal EEGs showed multifocal spikes. Ictal recordings in six
      showed electrodecremental events. CONCLUSIONS: Recurrent spasms after remission
      of West syndrome represent an extremely resistant, distressing form of epilepsy.
      The onset of West syndrome is age related, but it does not reliably vanish.

PMID- 14636335
TI  - Involvement of gap junctions in the manifestation and control of the duration of
      seizures in rats in vivo.
AB  - PURPOSE: The possible role of gap junctions in the manifestation and control of
      the duration of seizures was tested on the 4-aminopyridine-induced epilepsy model
      in rats in vivo, by using electrophysiologic, pharmacologic, and molecular
      biologic techniques. METHODS; In electrophysiologic experiments, the functional
      states of the gap junctions were manipulated with a specific blocker
      (carbenoxolone) or opener (trimethylamine) at the already active focus of adult,
      anesthetized rats, 60 min after the induction of the first seizure, which was
      repeated spontaneously thereafter. Semiquantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) amplification was used to measure the levels
      of connexin (Cx) 32, 43, and 36 messenger RNAs (mRNAs) prepared from the areas of
      the already active primary and mirror foci. RESULTS: After repeated seizures, the
      expression levels of Cx32, Cx43, and Cx36 mRNAs at the epileptic foci were
      increased significantly. Blockade of the gap junctions with carbenoxolone
      shortened the duration of seizures and decreased the amplitude of the seizure
      discharges, whereas their opening with trimethylamine lengthened the duration and
      increased the amplitude. Secondary epileptogenesis was facilitated when the gap
      junctions were opened. CONCLUSIONS; Our findings support the idea that, in
      epileptic foci, the gap junctions are involved in the expression of rhythmic
      ictal discharges and in the control of the duration and propagation of the
      individual seizures in vivo.

PMID- 14636336
TI  - Increased persistent sodium currents in rat entorhinal cortex layer V neurons in
      a post-status epilepticus model of temporal lobe epilepsy.
AB  - PURPOSE: Spontaneous seizures in rats emerge several weeks after induction of
      status epilepticus with pharmacologic treatment or electrical stimulation,
      providing an animal model for human temporal lobe epilepsy. In this study, we
      investigated whether status epilepticus caused changes in the function of voltage
      gated sodium channels in entorhinal cortex layer V neurons, a cellular group
      important for the genesis of limbic seizures. METHODS: We induced status
      epilepticus in rats, by using lithium-pilocarpine, and then 2-12 weeks later,
      used whole-cell voltage-clamp to examine voltage-activated sodium currents of
      acutely dissociated layer V neurons. RESULTS: Transient sodium currents of
      entorhinal cortex layer V neurons isolated from 9- to 12-week post-status
      epilepticus rats were similar to currents in age-matched controls; however, low
      threshold persistent sodium currents were significantly larger. This increase in
      persistent activity was not seen 2-3 weeks after pilocarpine treatment; thus it
      occurred after a delay comparable to the delay in the appearance of spontaneous
      seizures. CONCLUSIONS: Increased persistent currents are expected to accentuate
      neuronal excitability and thus may contribute to the genesis of spontaneous
      seizures after status epilepticus.

PMID- 14636337
TI  - Focal cooling suppresses continued activity of epileptic focus in patients with
      partial status epilepticus.

PMID- 14636338
TI  - The predictive value of the type of seizure onset in infants with epileptic
      spasms and partial seizures within a single ictal event.

PMID- 14636339
TI  - Serum insulin and leptin levels and valproate-associated obesity.

PMID- 14636340
TI  - Neuronal death in mesial temporal sclerosis: separating morphology from
      mechanism.

PMID- 14636342
TI  - Effects of antiepileptic drugs on refractory seizures in the intact immature
      corticohippocampal formation in vitro.
AB  - PURPOSE: We developed a new in vitro preparation of immature rats, in which
      intact corticohippocampal formations (CHFs) depleted in magnesium ions become
      progressively epileptic. The better to characterize this model, we examined the
      effects of 14 antiepileptic drugs (AEDs) currently used in clinical practice.
      METHODS: Recurrent ictal-like seizures (ILEs, four per hour) were generated in
      intact CHFs of P7-8 rats, and extracellular recordings were performed in the
      hippocampus and neocortex. AEDs were applied at clinically relevant
      concentrations (at least two), during 30 min after the third ILE. Their ability
      to prevent or to delay the next ILE was examined. RESULTS: Valproic acid and
      benzodiazepines (clobazam and midazolam) but also phenobarbital and levetiracetam
      prevent the occurrence of seizures. In contrast, usual concentrations of
      carbamazepine (CBZ), phenytoin, vigabatrin, tiagabine, gabapentin, lamotrigine
      (LTG), topiramate, felbamate, and ethosuximide did not suppress ILEs. In
      addition, LTG and CBZ aggravate seizures in one third of the cases. CONCLUSIONS:
      This intact in vitro preparation in immature animals appears to be quite
      resistant to most AEDs. Blockade of seizures was achieved with drugs acting
      mainly at the gamma-aminobutyric acid (GABA)A-receptor site but not with those
      that increase the amount of GABA. Drugs with a broad spectrum of activity are
      efficient but not those preferentially used in partial seizures or absences. We
      suggest that this preparation may correspond to a model of epilepsy with
      generalized convulsive seizures and could be helpful to develop new AEDs for
      refractory infantile epilepsies.

PMID- 14636343
TI  - Valproate suppresses status epilepticus induced by 4-aminopyridine in CA1
      hippocampus region.
AB  - PURPOSE: We investigated the effects of valproate (VPA) on an in vivo model of
      status epilepticus (SE) induced by intrahippocampal application of 4
      aminopyridine (4-AP). METHODS: To induce continuous epileptiform activity without
      a clinical component, 4-AP (100 mM) was slowly injected in the hippocampus of
      adult rats. Extracellular field potential from the CA1 region of the rat
      hippocampus was recorded to assess abnormal epileptiform activity. Once the SE
      seizures were induced by 4-AP, the test drug was injected. In some experiments to
      test the ability of a drug to prevent the induction of SE, the drug was
      administered before 4-AP injection. RESULTS: Intrahippocampal injection of 4-AP
      induced continuous epileptic activity without a clinical component that lasted
      >60 min. The intravenous injection of 400-600 mg/kg VPA rapidly (approximately
      100 s) abolished the SE, and this effect persisted for >/=4 h in our experimental
      model. The intravenous injection of 100-300 mg/kg VPA did not abolish previously
      induced SE, but prevented the appearance of SE when applied before the induction
      of SE. The intravenous injection of 80 mg/kg phenytoin or carbamazepine did not
      abolish or prevent SE. CONCLUSIONS: We conclude that 4-AP-induced SE was
      suppressed by VPA at 400-600 mg/kg, whereas minor doses (100-300 mg/kg) only
      prevent the 4-AP-induced SE. Present results suggest the revisiting of VPA as a
      useful drug for the treatment of SE.

PMID- 14636344
TI  - Recurrent nonstatus generalized seizures alter the developing chicken brain.
AB  - PURPOSE: Noninvasive magnetic resonance imaging was used to assess the evolution
      of seizure-induced pathology in epileptic, carrier, and normal chickens. Our
      objective was to determine whether repetitively evoked seizures in an epileptic
      fowl model of generalized seizures resulted in altered brain development.
      METHODS: Data were obtained from seizure and control groups at 45, 90, and 180
      days after hatching. RESULTS: At 180 days, apparent diffusion coefficient (ADC)
      values in the optic tectum and archistriatum of the stimulated epileptic chicks
      were reduced, whereas ADC values in the nonstimulated group remained unchanged.
      The mean brain volume of epileptic chickens from the stimulated group was smaller
      than that from the nonstimulated group at 90 and 180 days. CONCLUSIONS: These
      findings establish that recurrent seizures modify the brain matrix.

PMID- 14636345
TI  - Major vault protein, a marker of drug resistance, is upregulated in refractory
      epilepsy.
AB  - PURPOSE: The molecular basis of drug resistance in epilepsy is being explored.
      Two proteins associated with drug resistance in cancer, P-glycoprotein and
      multidrug resistance-associated protein 1, are upregulated in human epileptogenic
      pathologies. Other proteins associated with resistance in cancer include major
      vault protein (MVP) and breast cancer resistance protein (BCRP). We hypothesized
      that these proteins would also be upregulated in human epileptogenic pathologies.
      METHODS: Hippocampal sclerosis (HS), focal cortical dysplasia (FCD), and
      dysembryoplastic neuroepithelial tumor (DNT) were studied by using
      immunohistochemistry for MVP and BCRP. Nonepileptogenic control and
      histologically normal brain adjacent to epileptogenic tissue were used for
      comparison. RESULTS: MVP and BCRP were expressed ubiquitously in brain capillary
      endothelium. Ectopic upregulation of MVP was seen in hilar neurons in HS,
      dysplastic neurons in FCD, and lesional neurons in DNT. Only in HS cases were
      rare extralesional neurons immunoreactive. Glial upregulation was not seen. There
      was no qualitative upregulation of BCRP. CONCLUSIONS: These results show that
      more than one resistance protein may be upregulated in a given epileptogenic
      pathology and may contribute to drug resistance. Determination of the types,
      amounts, and distribution of such proteins will be necessary for rational
      treatment for drug resistance in epilepsy.

PMID- 14636346
TI  - Short course of prednisolone in Indian patients with solitary cysticercus
      granuloma and new-onset seizures.
AB  - PURPOSE: To evaluate the role of a short course of oral corticosteroids in Indian
      patients with solitary cysticercus granuloma with seizures. METHODS: In this open
      label, randomized, prospective follow-up study, 97 patients with new-onset
      seizures and a single enhancing computed tomography (CT)-detected lesion of
      cysticercosis were randomly divided in two groups to receive either antiepileptic
      monotherapy alone (n = 48) or antiepileptic monotherapy with prednisolone (n =
      49). The patients in the latter group received prednisolone, 1 mg/kg/day for 10
      days, followed by tapering over next 4 days. The patients were followed up for 6
      months. Repeated CT scans were performed after 1 and 6 months. RESULTS: The
      majority of patients were young. Simple partial seizure, with or without
      secondary generalization, was the commonest seizure type encountered. Follow-up
      CT scans at 1 and 6 months demonstrated a significantly better response for
      prednisolone as far as complete resolution of CT lesion was concerned. Kaplan
      Meier analysis suggested significantly less probability of seizure recurrence for
      prednisolone-treated patients. At 6 months, Kaplan-Meier estimated risk of
      seizure after first seizure was 2% in prednisolone-treated patients in comparison
      to 13% for those who were not given prednisolone. CONCLUSIONS: Short-term
      prednisolone therapy helps in rapid resolution of solitary cysticercus granuloma
      in Indian patients with new-onset seizures. Resolution of lesions is associated
      with improved seizure-related prognosis.

PMID- 14636347
TI  - Thalamic dysfunction in juvenile myoclonic epilepsy: a proton MRS study.
AB  - PURPOSE: To investigate neuronal dysfunction in the thalami of patients with
      juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy
      (MRS). METHODS: We performed single-voxel proton MRS over the right and the left
      thalami of 10 consecutive patients (five women) with JME (mean age, 31.6 years)
      and 10 age-matched healthy volunteers (five men). All patients had seizure onset
      in late childhood-teenage, normal neurologic examination, typical EEG of JME, and
      normal high-resolution MR imaging (MRI). We determined ratios of N
      acetylaspartate (NAA) over creatine-phosphocreatine (Cr). Values <2 standard
      deviations from controls were considered abnormal. We performed analysis of
      variance to evaluate group differences. RESULTS: Group analysis showed that
      thalami NAA/Cr ratios were significantly decreased in JME patients (left side,
      1.58 +/- 0.26; right side, 1.5 +/- 0.15) as compared with controls (left side,
      1.98 +/- 0.18; right side, 1.88 +/- 0.15; p = 0.001 and p = 0.007, respectively).
      Individual analysis showed that nine of the 10 patients had abnormal NAA/Cr in at
      least one of the thalami. CONCLUSIONS: This study shows evidence of neuronal
      dysfunction in the thalami of patients with JME, which may have relevance for the
      mechanisms of seizure generation in this form of generalized epilepsy.

PMID- 14636348
TI  - Mental tasks induce gamma EEG with reduced responsiveness in primary generalized
      epilepsies.
AB  - PURPOSE: We previously revealed an interictal increase in intensity of EEG
      rhythms during quiescent mental activity in the 30- to 100-Hz frequency (gamma)
      range in primary generalized epilepsy (PGE). We have evidence that there is
      induction of gamma EEG in normal subjects in response to controlled mental
      activity. Here we test whether mental tasks further augment interictal gamma
      oscillations in people with PGE. METHODS: We recorded interictal EEG from
      patients with PGE and partial epilepsy and compared EEG power spectral responses
      (increases over resting) during mental tasks. RESULTS: In partial epilepsy,
      mental tasks (except for alternating checkerboard visual stimulation) induced 1.5
      to 2.5-fold increases in power of gamma EEG. In generalized epilepsy,
      generalized increases of 1.5-fold in gamma EEG were induced by only two mental
      tasks (reading and subtraction), and enhancement of 1- to 1.5-fold in the
      remaining six (checkerboard, expectancy, music, learning, recalling, and a
      video). CONCLUSIONS: Gamma EEG is less responsive to mental activation in PGE
      than in partial epilepsy, confirming an abnormality in gamma mechanisms in PGE.
      Our findings also provide a possible mechanistic link between mental activity and
      seizures in reading- and arithmetic-induced seizures.

PMID- 14636349
TI  - Physiology of human cortical neurons adjacent to cavernous malformations and
      tumors.
AB  - PURPOSE: Focal neocortical seizures can be associated with a number of specific
      pathologies including supratentorial tumors and cavernous malformations (CMs),
      both of which are highly epileptogenic. METHODS: To begin to address the question
      of whether these lesions have different mechanisms of epileptogenesis, we used
      intracellular recordings from neurons adjacent to intracerebral neoplasms and
      cerebral CMs. Developmental anomalies were not included in this study. RESULTS:
      Neurons adjacent to CMs had a greater propensity to show large (>5 mV), complex
      spontaneous synaptic events than did neurons neighboring neoplastic substrates
      (50 vs. 4.7% of cells and 75 and 8% of patients, respectively; p < 0.004; p <
      0.05). Both spontaneous excitatory and inhibitory events were noted. In contrast,
      in tissue adjacent to tumors, low-amplitude (<3 mV) spontaneous excitatory
      activity predominated. Neurons neighboring CMs also exhibited more excitable
      responses to synaptic stimulation, with multiple action potentials riding on
      prolonged excitatory postsynaptic potentials (EPSPs) being evoked in 71% of these
      cells, versus 32% of cells from the tumor group; p < 0.05. In studies using
      hippocampal tissue, we noted a similar pattern of spontaneous activity in tissue
      adjacent to CMs. CONCLUSIONS: These data suggest that CMs may induce seizure
      activity via a different pathophysiologic mechanism(s) than glial tumors.

PMID- 14636350
TI  - Seizure outcome after temporal lobectomy in temporal lobe cortical dysplasia.
AB  - PURPOSE: To identify the temporal lobe cortical dysplasia (CD) histopathology
      classification subtype and determine the seizure outcome of patients who
      underwent temporal lobectomy with coincident CD. METHODS: We reviewed the data of
      28 patients with temporal lobe epilepsy who underwent surgery with pathologically
      verified CD at our institution from 1990 to 2000. The seizure outcome was
      assessed at a minimum of 1 year after surgery according to Engel's
      classification. RESULTS: Of 28 patients who underwent surgery, nine (32.1%) had
      isolated CD, and 19 (67.9%) had CD and hippocampal sclerosis (CD&HS). Twenty-six
      (92.9%) patients had histopathology subtype Ia (architectural abnormalities).
      Twenty (71.4%) patients were seizure free (Engel class I). Favorable seizure
      outcome (Engel class I, II) was achieved in 26 (92.9%) patients. No difference in
      seizure outcome was noted between patients with CD and CD&HS. CONCLUSIONS: The
      most common histopathologic subtype in patients with temporal lobe CD is type Ia
      (architectural abnormalities). Temporal lobectomy in temporal lobe epilepsy
      patients with CD can achieve favorable seizure outcome.

PMID- 14636351
TI  - The multicenter study of epilepsy surgery: recruitment and selection for surgery.
AB  - PURPOSE: Multiple studies have examined predictors of seizure outcomes after
      epilepsy surgery. Most are single-center series with limited sample size. Little
      information is available about the selection process for surgery and, in
      particular, the proportion of patients who ultimately have surgery and the
      characteristics that identify those who do versus those who do not. Such
      information is necessary for providing the epidemiologic and clinical context in
      which epilepsy surgery is currently performed in the United States and in other
      developed countries. METHODS: An observational cohort of 565 surgical candidates
      was prospectively recruited from June 1996 through January 2001 at six
      Northeastern and one Midwestern surgical centers. Standardized eligibility
      criteria and protocol for presurgical evaluations were used at all seven sites.
      RESULTS: Three hundred ninety-six (70%) study subjects had resective surgery.
      Clinical factors such as a well-localized magnetic resonance imaging (MRI)
      abnormality and consistently localized EEG findings were most strongly associated
      with having surgery. Of those who underwent intracranial monitoring (189, 34%),
      85% went on to have surgery. Race/ethnicity and marital status were marginally
      associated with having surgery. Age, education, and employment status were not.
      Demographic factors had little influence over the surgical decision. More than
      half of the patients had intractable epilepsy for >/=10 years and five or more
      drugs had failed by the time they initiated their surgical evaluation. During the
      recruitment period, eight new antiepileptic drugs were approved by the Food and
      Drug Administration for use in the United States and came into increasing use in
      this study's surgical candidates. Despite the increased availability of new
      therapeutic options, the proportion that had surgery each year did not fluctuate
      significantly from year to year. This suggests that, in this group of patients,
      the new drugs did not provide a substantial therapeutic benefit. CONCLUSIONS: Up
      to 30% of patients who undergo presurgical evaluations for resective epilepsy
      surgery ultimately do not have this form of surgery. This is a group whose needs
      are not currently met by available therapies and procedures. Lack of clear
      localizing evidence appears to be the main reason for not having surgery. To the
      extent that these data can address the question, they suggest that repeated
      attempts to control intractable epilepsy with new drugs will not result in
      sustained seizure control, and eligible patients will proceed to surgery
      eventually. This is consistent with recent arguments to consider surgery earlier
      rather than later in the course of epilepsy. Postsurgical follow-up of this group
      will permit a detailed analysis of presurgical factors that predict the best and
      worst seizure outcomes.

PMID- 14636352
TI  - Outcome at adulthood of the continuous spike-waves during slow sleep and Landau
      Kleffner syndromes.
AB  - PURPOSE: The aim of this study was to determine the clinical, social, and/or
      professional and cognitive outcomes in adulthood of the continuous spike-waves
      during slow sleep (CSWS) and Landau-Kleffner syndromes, which are two rare
      epileptic syndromes occurring in children. METHODS: We enrolled seven young
      adults, five who had a CSWS syndrome, and two, a Landau-Kleffner syndrome in
      childhood. We evaluated their intellectual level as well as their oral and
      written language and executive functions. RESULTS: This study confirmed that the
      epilepsy associated with these syndromes has a good prognosis. Only one patient
      still had active epilepsy. However, the neuropsychological disorders particular
      to each syndrome persisted. Only two patients had followed a normal pathway in
      school. Three of the five patients with a CSWS syndrome during childhood remained
      globally and nonselectively mentally deficient. We found no evidence of the
      persistence of a dysexecutive syndrome in this study group. The intellectual
      functions of the two patients with Landau-Kleffner syndrome were normal; however,
      their everyday lives were disrupted by severe, disabling language disturbances.
      We discuss the role of some prognostic factors such as the location of the
      interictal electric focus and the age at onset of CSWS. CONCLUSIONS: These two
      epileptic syndromes of childhood are very similar in many respects, but their
      clinical outcomes in adulthood are different.

PMID- 14636353
TI  - Episousse: incidence of newly presenting seizures in children in the Region of
      Sousse, Tunisia.
AB  - PURPOSE: To evaluate the incidence of newly presenting seizures in children in
      the area of Sousse, Tunisia. METHODS: From June 1, 1998, to May 31, 1999, all
      children aged 1 month to 15 years with first provoked and unprovoked seizures
      were included. Children with febrile seizures were excluded. All suspected cases
      were systematically referred to the Department of Functional Explorations of the
      Nervous System where a detailed questionnaire was filled out by a neurologist.
      All the patients underwent an EEG. Only 12 patients had a computed tomography
      (CT) scan. RESULTS: A total of 175 patients were included. Eighteen (10.3%)
      patients had acute symptomatic seizures, and 157 patients had unprovoked
      seizures. The incidence rate of first unprovoked seizures was 102.1/100,000. In
      this latter group, some epileptic syndromes were individualized on strict
      electroclinical criteria. CONCLUSIONS: However, nearly 75% of the cases remained
      cryptogenic, one of the major reasons that no predominant risk factor was
      identified in this population.

PMID- 14636354
TI  - Epilepsy and multiple sclerosis in Sicily: a population-based study.
AB  - PURPOSE: To evaluate the association between epilepsy and multiple sclerosis
      (MS), we analyzed the incidence of epilepsy in a population-based incidence
      cohort of MS in Catania, Sicily. METHODS: According to Poser's diagnostic
      criteria, 170 incident cases of MS have been identified from 1975 to 1994 in the
      city of Catania. All these subjects underwent a complete neurological examination
      to confirm the diagnosis of MS and to identify those patients with a history of
      seizures. Diagnosis of epilepsy was based on the criteria proposed by the
      International League Against Epilepsy (ILAE) in 1993, and seizures were
      classified according to the classification of the ILAE, 1981. RESULTS: From 1975
      to 1994, 170 subjects with MS had the clinical onset of the disease. The mean
      annual incidence of MS was 2.3/100,000 (95% CI, 2.0-2.6). Of the 170 defined MS
      patients, four developed epilepsy after the onset and also diagnosis of MS,
      giving an incidence rate of epilepsy of 285/100,000 person years at risk (95% CI,
      119-684) and 147.8/100,000 when age adjusted to the world standard population.
      The cumulative risk of developing epilepsy after the onset of MS, evaluated by
      using the life-table methods, was zero at 1 year and 1.76% at 5 years. Of these
      four patients, three were classified as having partial seizures with secondary
      generalization and one with tonic-clonic seizures. CONCLUSIONS: Our data are
      consistent with those reported in literature suggesting that the risk of
      developing epilepsy is threefold higher among MS patients than in the general
      population.

PMID- 14636355
TI  - Knowledge of epilepsy and familiarity with this disorder in the U.S. population:
      results from the 2002 HealthStyles Survey.
AB  - PURPOSE: To assess perceptions of knowledge and experience with epilepsy and
      seizures in the U.S. population to develop communication campaigns to improve the
      public's understanding of epilepsy. In a national survey, focal points included
      the public's knowledge of the disorder, whether people know someone who has it,
      exposure to epilepsy-related information, and knowledge about how to respond to a
      person having a seizure. METHODS: The Epilepsy Program of the Centers for Disease
      Control and Prevention included nine items on an annual mail survey that targeted
      a representative sample of the U.S. population. Data were weighted to be
      representative of the U.S. population. chi2 analyses were performed, and
      standardized residuals were used to examine the associations between responses
      and demographic variables. RESULTS: Responses were obtained from 4,397 persons.
      Despite the low prevalence of epilepsy, results indicate that about half of all
      persons have witnessed an epileptic seizure either in person or on television;
      about one third of all persons know someone with epilepsy, but relatively few are
      familiar with epilepsy, how to respond to a seizure, or with the Epilepsy
      Foundation. CONCLUSIONS: In general, the public has relatively little knowledge
      about epilepsy. Educational campaigns that inform the public about this disorder
      and about seizures should work through community settings to improve the general
      public's understanding of epilepsy.

PMID- 14636356
TI  - Analysis of cerebrospinal fluid glial fibrillary acidic protein after seizures in
      children.
AB  - PURPOSE: To evaluate pediatric seizure patients for astrocytic injury by
      measuring cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP),
      determine risk factors for GFAP elevation after seizures, and compare seizure
      induced astrocyte injury with neuronal injury by concurrent measurement of CSF
      neuron-specific enolase (NSE). METHODS: CSF obtained from pediatric patients (n =
      52) within 24 h of seizure was assayed for GFAP and NSE. Retrospective chart
      review was performed for seizure type, duration, and etiology. RESULTS: Overall,
      children with seizures had elevated CSF GFAP compared with controls (p = 0.0075),
      but no elevation of NSE (p = 0.1437). No effect of seizure type or etiology was
      found, but a significant positive effect of seizure duration (p = 0.0010) and
      status epilepticus (p = 0.0296) was seen on CSF GFAP. Individually, seven
      children (13%) had elevated GFAP (>440 pg/ml); in five children, the increased
      GFAP was not accompanied by elevations in NSE (<12 ng/ml). Five children with
      elevated GFAP had symptomatic etiologies for their seizures, but the etiology of
      one child with elevated GFAP was cryptogenic, and one had febrile seizures.
      CONCLUSIONS: Elevation of CSF GFAP after seizures suggests that astrocytic injury
      may occur in a subgroup of children, primarily in the context of prolonged
      seizures and symptomatic etiologies. Increased GFAP levels may occur in patients
      with normal NSE, suggesting that GFAP may be a more sensitive marker of brain
      injury in some cases.

PMID- 14636357
TI  - Infantile spasms in a patient with williams syndrome and craniosynostosis.
AB  - A patient with Williams syndrome, craniosynostosis, and infantile spasms is
      described. At age 6 months, the infant demonstrated infantile spasms and
      craniosynostosis and was operated on for craniosynostosis and treated with
      adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely
      controlled the seizures, but was halted because of the progression of ventricular
      hypertrophy. The seizure returned, and he was found to have elfin face, failure
      to-thrive, developmental delay, and dental malformation in addition to congenital
      heart defects. High-resolution chromosome analysis revealed interstitial deletion
      of 7q11.22-q11.23. Therefore his clinical and cytogenetic diagnosis was Williams
      syndrome. Thyrotropin-releasing hormone (TRH) therapy reduced his seizures and
      improved the findings of EEG without cardiac side effects. In addition, his
      psychomotor development was slightly improved.

PMID- 14636358
TI  - Retraction for misappropriation: brain tumor and seizures: pathophysiology and
      its implications for treatment revisited Bernhard Schaller and Stephan J. Ruegg
      Epilepsia 2003;44:1223-1232.

PMID- 14636359
TI  - Letter of apology.

PMID- 14636361
TI  - Introduction to special issue on antidepressant use in bipolar disorder.

PMID- 14636362
TI  - Antidepressant monotherapy for bipolar type II major depression.
AB  - OBJECTIVES: Bipolar type II (BP II) disorder is thought to be distinct from BP I
      disorder on genetic and biological grounds, and it is not merely a milder form of
      the illness. It affects 1.5-2.5% of the US adult population, and is characterized
      by highly recurrent depressive episodes with a substantial morbidity from
      alcoholism and non-affective psychopathology, and a higher suicide rate than
      either BP I or unipolar depression. Treatment recommendations for BP II
      depression are based upon concerns over drug-induced manic-switch episodes, and
      suggest using either a mood stabilizer alone or a combination of an SSRI plus a
      mood stabilizer. Recent evidence, however, indicates that the rate of manic
      switch episodes may be modest in BP II patients. Recent studies have provided
      evidence that antidepressant monotherapy may be an effective initial and long
      term treatment for BP II major depression with a low manic-switch rate. METHODS:
      In this article, we review the recent literature on BP II disorder, with a focus
      on the treatment of BP II major depression. RESULTS: We present a summary of data
      from recent studies by our group and others indicating that antidepressant
      monotherapy for BP II depression may be safe and effective with a low manic
      switch rate. CONCLUSION: Antidepressant monotherapy may be beneficial for some
      patients with BP II major depression.

PMID- 14636363
TI  - A re-evaluation of the role of antidepressants in the treatment of bipolar
      depression: data from the Stanley Foundation Bipolar Network.
AB  - OBJECTIVES: The risk-to-benefit ratio of the use of unimodal antidepressants
      (ADs) as adjuncts to mood stabilizers continues to be an area of controversy and
      disagreement among experts in the field. This paper reviews new data on: (1)
      depression in bipolar illness, (2) switch rates on ADs and (3) risks of AD
      discontinuation that are pertinent to the ongoing discussion and recommendations.
      METHODS: In the first study reviewed, 258 outpatients with bipolar illness were
      assessed prospectively on a daily basis using the National Institute of Mental
      Health-Life Chart Method (NIMH-LCM) for 1 year. In the second study, 127 bipolar
      depressed patients were randomized to 10 weeks of sertraline, bupropion, or
      venlafaxine, as adjuncts to mood stabilizers; non-responders were re-randomized
      and responders were offered a year of continuation treatment. In the final study,
      Altshuler et al. retrospectively and prospectively assessed the risk of
      depressive relapses in patients who remained on ADs after 2 months of euthymia
      compared with those who discontinued ADs. RESULTS: Despite intensive naturalistic
      treatment, the 258 outpatients with bipolar illness followed prospectively for 1
      year showed three times as many days depressed as days manic, re-emphasizing the
      considerable depressive morbidity that remains in bipolar disorder despite the
      number of treatment options available. In the study of bipolar depressed patients
      randomized to one of three ADs, a range of severities and durations of hypomanic
      to manic switches were discerned following 175 trials of AD augmentation of
      treatment with a mood stabilizer. Of the acute 10-week trials, 9.1% were
      associated with switches into hypomania or mania and another 9.1% with a week or
      more of hypomania alone (with no to minimal dysfunction). In 73 continuation
      phase AD trials, 16.4 and 19.2% were similarly associated with hypomanic to manic
      and hypomanic switches, respectively. In the Altshuler et al. studies, those who
      remained well on any AD for more than 2 months (only 15-20% of those initially
      treated) and who continued on ADs showed a lesser rate of relapse into depression
      over 1 year (35 and 36% in the first and second study, respectively) compared
      with those who discontinued their ADs (68 and 70% relapsing into depression).
      Surprisingly, this continuation of ADs was associated with no increase in the
      rate of switching into mania compared with those stopping ADs. CONCLUSIONS: These
      data reveal that depression and depressive cycling remain a substantial problem
      in some two-thirds of intensively treated bipolar outpatients. Acute AD
      augmentation was associated with a modest response rate and 18.2% switched into a
      hypomanic to manic episode, and 35.6% of the continuation trials showed these two
      types of switches. Two separate studies suggest that in the very small subgroup
      who remain well on ADs for at least 2 months, one should consider continuation of
      this AD augmentation treatment, because AD discontinuation appears associated
      with a substantially increased risk of depression relapse over the subsequent
      year with no reduced risk of switching into mania.

PMID- 14636364
TI  - Antidepressant-induced mania: an overview of current controversies.
AB  - OBJECTIVE: The prevalence, characteristics, and possible risk factors associated
      with antidepressant-induced mania remain poorly described. The present review
      sought to identify published rates of antidepressant-induced mania and describe
      risk factors for its emergence. METHODS: A MedLine search was conducted of
      journals that focused on mania or hypomania associated with recent antidepressant
      use. Data from published reports were augmented with relevant findings from
      recent clinical trials presented at scientific conferences. RESULTS:
      Antidepressant-induced manias have been reported with all major antidepressant
      classes in a subgroup of about 20-40% of bipolar patients. Lithium may confer
      better protection against this outcome when compared with other standard mood
      stabilizers, although switch rates have been reported with comparable frequencies
      on or off mood stabilizers. Evidence across studies most consistently supports an
      elevated risk in patients with (i) previous antidepressant-induced manias, (ii) a
      bipolar family history, and (iii) exposure to multiple antidepressant trials.
      CONCLUSION: About one-quarter to one-third of bipolar patients may be inherently
      susceptible to antidepressant-induced manias. Bipolar patients with a strong
      genetic loading for bipolar illness whose initial illness begins in adolescence
      or young adulthood may be especially at risk. Further efforts are needed to
      better identify high-vulnerability subgroups and differentiate illness-specific
      from medication-specific factors in mood destabilization.

PMID- 14636365
TI  - Antidepressants in bipolar disorder: the case for caution.
AB  - The 2002 American Psychiatric Association (APA) guidelines for the treatment of
      bipolar disorder recommended more conservative use of antidepressants. This
      change in comparison with previous APA guidelines has been criticized, especially
      from some groups in Europe. The Munich group in particular has published a
      critique of assumptions underlying the conservative recommendations of the recent
      APA treatment guidelines. In this paper, we re-examine the argument put forward
      by the Munich group, and we demonstrate that indeed, conceptually and
      empirically, there is a strong rationale for a cautious approach to
      antidepressant use in bipolar disorder, consistent with, and perhaps even more
      strongly than, the APA guidelines. This rationale is based on support for the
      following four propositions: (i) The risk of antidepressant induced mood-cycling
      is high, (ii) Antidepressants have not been shown to definitively prevent
      completed suicides and reduce mortality, whereas lithium has, (iii)
      Antidepressants have not been shown to be more effective than mood stabilizers in
      acute bipolar depression and have been shown to be less effective than mood
      stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood
      stabilizers, especially lithium and lamotrigine, have been shown to be effective
      in acute and prophylactic treatment of bipolar depressive episodes. We therefore
      draw three conclusions from this interpretation of the evidence: (i) There are
      significant risks of mania and long-term worsening of bipolar illness with
      antidepressants, (ii) Antidepressants should generally be reserved for severe
      cases of acute bipolar depression and not routinely used in mild to moderate
      cases and (iii) Antidepressants should be discontinued after recovery from the
      depressive episode, and maintained only in those who repeatedly relapse after
      antidepressant discontinuation (a minority we judge to represent only about 15
      20% of bipolar depressed patients).

PMID- 14636366
TI  - Case for caution, case for action.

PMID- 14636367
TI  - The bipolar spectrum: a clinical perspective.
AB  - The relative misdiagnosis and underdiagnosis of bipolar disorder is due in part
      to the 'soft' symptoms of bipolarity that characterize patients with non
      classical bipolar disorder. While no agreement has been reached on the term for
      this group of patients, the most common classification used is 'bipolar
      spectrum', which shifts the emphasis in diagnosis away from polarity and toward
      other diagnostic validators. In order to recognize and properly treat patients
      with bipolar disorder, clinicians should focus on careful evaluation of patients
      with mixed anxiety/depressive symptoms or impulsivity conditions (substance
      abuse, borderline personality, bulimia, and attention deficit disorder).
      Furthermore, in the treatment of bipolar disorder, clinicians should also
      recognize that antidepressants can have a negative effect on patients by
      increasing the likelihood of more severe rapid cycling. While antidepressants may
      be useful in particularly difficult cases, emphasis should be placed on mood
      stabilizers for treatment of the bipolar spectrum.

PMID- 14636368
TI  - The strengths and weaknesses of the concept 'bipolar spectrum'.

PMID- 14636369
TI  - Mood-stabilizers: the archeology of the concept.
AB  - OBJECTIVE: To review the history of 'mood-stabilizing' treatments. METHOD: We
      have reviewed primary source data on the origin of the use of current mood
      stabilizers. RESULTS: This historical record on the origins of the mood
      stabilizers points to a more ambiguous picture as regards pharmacotherapeutic
      specificity to bipolar disorders than is commonly conceded. CONCLUSIONS: This
      review suggests a need for alternative formulations of the concept of a mood
      stabilizer. An alternative to the currently dominant paradigm is that these
      agents have treatment effects, which need to be matched more precisely with
      patients' constitutional types in order to optimize outcomes.

PMID- 14636370
TI  - "Mood-stabilizers: the archeology of the concept"--by M Harris, S Chandran, N
      Chakraborty and D Healy: a commentary.

PMID- 14636371
TI  - Clinical consequences of under-recognized bipolar spectrum disorder.
AB  - The prevalence of bipolar disorder is higher than previously believed, especially
      when bipolar spectrum disorders (BSD) are taken into account, and may approach
      rates as high as 5%. Difficulties in diagnosing bipolar II and BSD arise from
      complexities associated with defining and diagnosing hypomania. Additionally,
      bipolar disorder and BSD are often misdiagnosed because of symptoms that overlap
      with other psychiatric disorders, particularly unipolar depression. Recognition
      of the broader spectrum of bipolar disorders and their adequate treatment is
      paramount because bipolar disorder exacts such a high personal and societal toll,
      with high rates of suicide and interpersonal problems and a substantial economic
      burden. Recognition can be improved with active screening, and screening tools
      such as the Mood Disorders Questionnaire can be easily included in the initial
      assessment of patients who present with depressive symptoms. Depressive episodes
      are common in patients who experience BSDs, and increasingly treatment approaches
      designed specifically for bipolar depression are being studied.

PMID- 14636372
TI  - Prophylactic effect of phenytoin in bipolar disorder: a controlled study.
AB  - OBJECTIVE: Phenytoin is an effective anticonvulsant that has not previously been
      studied prophylactically in bipolar (BP) patients. Thus a study of phenytoin
      prophylaxis was undertaken and is herein reported. METHOD: Bipolar patients were
      studied who had at least one episode per year in the previous 2 years despite
      ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13)
      before entering the study. Phenytoin or placebo was added to their current
      therapy in a double-blind cross-over design for 6 months in each phase. Thirty
      observation periods of 6 months each were studied for 23 patients. RESULTS: Three
      patients had relapse on phenytoin and nine had relapse on placebo. There was a
      significant prophylactic effect of phenytoin in BP disorder [Cox's F-test for
      comparing survival in two groups: F(6, 18) = 3.44, p = 0.02]. CONCLUSIONS: This
      study suggests prophylactic effects of add-on phenytoin in BP illness. However,
      the number of patients was small and confirmation is necessary.

PMID- 14636373
TI  - Polymorphism of the brain-derived neurotrophic factor gene and performance on a
      cognitive prefrontal test in bipolar patients.
AB  - OBJECTIVES: The aim of the study was to test a possible association between the
      Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene and
      performance on a neurocognitive test, the Wisconsin Card Sorting Test (WCST), in
      bipolar patients. METHODS: Fifty-four bipolar patients were studied, 18 male and
      36 female, aged 18-72 (mean 46 years). The number of perseverative errors (WCST
      P), non-perseverative errors (WCST-NP), completed corrected categories (WCST-CC),
      conceptual level responses (WCST-%CONC) and set to the first category (WCST-1st
      CAT) were measured in relation to the Val66Met genotypes of BDNF. RESULTS: The
      percentages of subjects with Val/Val, Val/Met and Met/Met genotypes were
      respectively 81.5, 16.7 and 1.8%. Subjects with Val/Val and Val/Met genotypes did
      not differ on clinical factors except for the age of onset of the illness, which
      was earlier in Val/Val than Val/Met genotype (27 years versus 38 years). The
      performance in all domains of WCST was significantly better in subjects with
      Val/Val BDNF genotype compared with Val/Met genotype. CONCLUSIONS: The results
      suggest a role of BDNF in prefrontal cognitive function in bipolar illness. The
      tests of prefrontal cognition may be considered as endophenotypic markers in
      bipolar illness.

PMID- 14636375
TI  - Introduction to the Royal Australian and New Zealand College of Psychiatrists
      clinical practice guidelines series.

PMID- 14636376
TI  - Australian and New Zealand clinical practice guidelines for the treatment of
      panic disorder and agoraphobia.
AB  - BACKGROUND: The Royal Australian and New Zealand College of Psychiatrists is co
      ordinating the development of clinical practice guidelines (CPGs) in psychiatry,
      funded under the National Mental Health Strategy (Australia) and the New Zealand
      Health Funding Authority. METHOD: For these guidelines, the CPG team reviewed the
      treatment outcome literature, consulted with practitioners and patients and
      conducted a meta-analysis of recent outcome research. TREATMENT RECOMMENDATIONS:
      Education for the patient and significant others covering: (i) the nature and
      course of panic disorder and agoraphobia; (ii) an explanation of the
      psychopathology of anxiety, panic and agoraphobia; (iii) rationale for the
      treatment, likelihood of a positive response, and expected time frame. Cognitive
      behaviour therapy (CBT) is more effective and more cost-effective than
      medication. Tricyclic antidepressants (TCAs) and serotonin selective reuptake
      inhibitors are equal in efficacy and both are to be preferred to benzodiazepines.
      Treatment choice depends on the skill of the clinician and the patient's
      circumstances. Drug treatment should be complemented by behaviour therapy. If the
      response to an adequate trial of a first-line treatment is poor, another evidence
      based treatment should be used. A second opinion can be useful. The presence of
      severe agoraphobia is a negative prognostic indicator, whereas comorbid
      depression, if properly treated, has no consistent effect on outcome.

PMID- 14636377
TI  - Fifty years of the double helix and its impact on psychiatry.
AB  - OBJECTIVE: To discuss the impact of Watson and Crick's double helix discovery on
      the field of psychiatry. METHOD: Psychiatric research studies using molecular
      genetic techniques are summarized. The implications of these findings in terms of
      our understanding and treatment of mental illness are discussed. RESULTS: There
      now exists growing evidence of candidate gene sites for a variety of psychiatric
      disorders ranging from schizophrenia to reading disability. CONCLUSIONS: The
      field of psychiatric genetics has become one of the most vital and productive
      areas of psychiatric research. New findings are continually coming to light,
      bringing us ever closer to understanding these complex disorders at a molecular
      level. Such knowledge could lead to improved drug treatments, screening of at
      risk individuals and even a reduction in the stigma attached to psychiatric
      disorders.

PMID- 14636378
TI  - Reflections on the 40th anniversary of the US Community Mental Health Centers
      Act.

PMID- 14636379
TI  - Forty years of progress in community mental health: the role of evidence-based
      practices.

PMID- 14636380
TI  - The 1973 deletion of homosexuality as a psychiatric disorder: 30 years on.

PMID- 14636381
TI  - Homosexuality and psychiatric nosology.

PMID- 14636382
TI  - Dropping the diagnosis of homosexuality: did it change the lot of gays and
      lesbians in Britain?

PMID- 14636383
TI  - Towards a psyche for psychiatry.
AB  - OBJECTIVE: To draw attention to the absence of a concept of personal existence in
      standard psychiatric approaches to mental illness. METHOD: To sketch a shift in
      Western consciousness which occurred suddenly before World War I, involving a
      banishment of such notions as self and the awareness of inner life from the
      discourse of psychiatry, psychology and philosophy, leaving a fundamental vacancy
      at the heart of these disciplines. RESULTS AND CONCLUSION: The positivist
      behaviourist hegemony of the twentieth century involved an implicit devaluation
      of that which is essentially human. The influence of this tradition brings with
      it the risk of an understanding and treatment of mental illness which leaves out
      issues at the core of humanity. I suggest we need to recover something of the
      manner of thinking of the great figures in psychological thought who were writing
      before the rise of behaviourism and who were contributing to the origins of
      dynamic psychiatry. A study of the phenomena of human consciousness was central
      to their work. Main figures mentioned include: Hughlings Jackson, the great
      neurologist who considered a career in philosophy; Pierre Janet, a philosopher
      turned psychiatrist; and William James, a physiologist who became a psychologist
      and philosopher.

PMID- 14636384
TI  - Categorical versus dimensional models of mental disorder: the taxometric
      evidence.
AB  - OBJECTIVE: To review studies of the categorical versus dimensional status of
      mental disorders that employ taxometric methodology. METHOD: A comprehensive
      qualitative review of all published taxometric studies of psychopathology.
      RESULTS: Categorical and dimensional models each receive well-replicated support
      for some groups of mental disorders. Studies favour categorical models for
      melancholia, eating disorders, pathological dissociation, and schizotypal and
      antisocial personality disorders. Dimensional models tend to be favoured for the
      broad neurotic spectrum--general depression, generalized anxiety, posttraumatic
      stress disorder--and for borderline personality disorder. CONCLUSIONS: Taxometric
      research clarifies the latent structure of psychopathology in ways that have
      implications for the classification, assessment, explanation and
      conceptualization of mental disorder.

PMID- 14636385
TI  - Atypical antipsychotic weight gain: a major clinical challenge.
AB  - OBJECTIVE: The major aim of this paper is to review findings from weight
      management intervention studies to consider clozapine and/or olanzapine induced
      weight gain. A parallel aim is to summarize the challenges facing future research
      and provide an overview of best practice in the management of weight in mental
      health patients. METHOD: A systematic literature search was conducted using
      Medline, Cinahl and PsychINFO data bases and reference lists from relevant
      published articles. Five studies which reported weight control practices in
      patients taking atypical antipsychotic medications were located and reviewed.
      RESULTS: The studies reviewed provide some important descriptive clinical
      insights; however, common shortcomings include small subject numbers and
      methodological drawbacks such as lack of a control group. CONCLUSIONS: There is
      some evidence that weight gain associated with atypical antipsychotic medication
      can be ameliorated by lifestyle changes such as improved nutritional practices
      and increased physical activity. Lifestyle interventions for individuals with
      psychotic disorders may need to be adapted to be most effective; for example,
      using strategies to counter increased appetite and to enhance physical activity.
      Clinicians need to be vigilant and persistent in monitoring and intervening if
      weight gain occurs. A standardized screening tool and clinical pathway would help
      clinicians to target appropriate interventions for each person prescribed
      atypical antipsychotic medication.

PMID- 14636386
TI  - Case managers' attitudes to the physical health of their patients.
AB  - OBJECTIVE: To examine the attitudes and practices of case managers working in
      Area Mental Health Services (AMHS) towards the physical health of people with
      chronic mental illness. METHOD: Case managers at four AMHS in Melbourne
      participated in focus groups and completed a survey questionnaire. RESULTS: Case
      managers generally believed that mental illness, psychotropic medication and
      lifestyle factors contributed to the poor physical health status of their
      patients. Although many case managers attempted interventions aimed at improving
      physical health, there was inconsistency regarding the areas targeted. Preventive
      health measures were often neglected. Overall, there was a sense of pessimism
      around whether improved physical health was possible for people with chronic
      mental illness. CONCLUSIONS: Lack of coordination among health professionals and
      the health system may contribute to the poor general health of people with mental
      illness. Patients often have difficulty accessing general practitioners and the
      culture within the AMHS can exclude considerations of physical health. Case
      management should include aspects addressing the physical health issues of AMHS
      clients.

PMID- 14636387
TI  - Right unilateral electroconvulsive therapy at six times seizure threshold.
AB  - OBJECTIVE: To examine the clinical practice of right unilateral electroconvulsive
      therapy (ECT) administered at six times seizure threshold (6 x RUL ECT). METHOD:
      A retrospective review of all patients who received 6 x RUL ECT between July 2000
      and June 2002. RESULTS: Twenty-one patients across a range of ages and diagnostic
      groups received D'Elia unilateral ECT at a seizure dosage at or above 388.8
      milliCoumbs (mC). In order to sustain predetermined criteria for seizure
      adequacy, energy was increased in 71% of patients. Final seizure lengths of 45 s
      electroencephalographic (EEG) activity, 28 s motor activity (cuffed) and a post
      ictal suppression index (PSI) of 83% were recorded. Eighty percent of patients
      responded after a mean of 7.0 treatments. Cognitive side-effects were noted in
      21% of patients. Fifty-two percent relapsed on average 6.3 months after the last
      treatment despite continuation pharmacotherapy. CONCLUSIONS: 6 x RUL ECT was
      found to be clinically effective, associated with cognitive side-effects and
      relapse. The debate over electrode placement is likely to continue.

PMID- 14636388
TI  - Can recovery-focused multimodal psychotherapy facilitate symptom and function
      improvement in people with treatment-resistant psychotic illness? A comparison
      study.
AB  - OBJECTIVE: To assess whether recovery-focused multimodal psychotherapy can
      facilitate symptom and function improvement in people with treatment-resistant
      psychotic illness. METHOD: Nine people with treatment-resistant schizophrenia or
      schizoaffective disorder whose symptoms and level of functioning necessitated
      inpatient care were engaged in individual multimodal psychotherapy for up to 21
      months. In addition to the multimodal therapy they also received standard
      inpatient care. Twelve people retrospectively matched for diagnosis, age, sex,
      and chronicity of illness, formed a comparison group. They also received standard
      inpatient care. The standard inpatient care for both experimental and comparative
      groups consisted of custodial care, predominantly atypical antipsychotic drug
      therapy, and ongoing care from a key worker. RESULTS: The treatment group showed
      clinically significant improvements in the overall Positive and Negative Symptom
      Scale (PANSS) scores which was significantly better than the changes found in the
      comparison group (p = 0.037). There was a 43% reduction in positive symptoms, a
      30% reduction in negative symptoms, a 27.5% reduction in general psychopathology
      symptoms and a 30% reduction in overall scores on the PANSS. General behaviour
      scores on the Rehabilitation Evaluation of Hall and Baker were clinically
      improved, with a 32% reduction, as were deviant scores, with a 93.3% reduction.
      The change in the deviant scores was significantly better in the treatment group
      (p = 0.025). CONCLUSION: Recovery-focused multimodal psychotherapy may facilitate
      symptom and function improvement in people with treatment-resistant psychotic
      illness.

PMID- 14636389
TI  - Does ethnicity affect need for mental health service among New Zealand prisoners?
AB  - OBJECTIVE: The National Study on Psychiatric Morbidity in New Zealand Prisons
      identified undiagnosed mental illness and unmet treatment needs for mentally
      disordered offenders. As approximately 50% of prisoners are of Maori and 8.3%
      Pacific Island ethnicity, we analyzed the data to determine if there were any
      differences in the rates of major mental disorders between ethnic groups. METHOD:
      A census of all female prisoners, all remand male prisoners and an 18% random
      sample of the sentenced male prisoners were interviewed employing the diagnostic
      interview for mental illness (CIDI-A), screening diagnostic interview for
      relevant personality disorders (PDQ) and suicide screening questions. Self
      identified ethnicity was recorded. Ethnic groups were compared for
      sociodemographic variables, morbidity for mental disorder, treatment experience
      and suicidality. RESULTS: The ethnic groups were largely similar in age and
      current prevalence for mental disorders, although there was some evidence of
      differing sociodemographic factors, especially younger age among the Maori
      prisoners. Maori report fewer suicidal thoughts, but acted suicidally at the same
      rate as non-Maori. Treatment for mental disorder was less common among Maori and
      Pacific Island prisoners than others, both in prison and in the community.
      CONCLUSION: Criminogenic factors present in the developmental histories of
      prisoners might also increase the risk of mental disorders. Ethnic groups were
      not different in the rate at which they manifest mental disorders in the face of
      such factors. Younger prisoners were disproportionately more likely to be of
      Maori or Pacific Island ethnicity. Both prior to and after entry to prison,
      services must improve responsiveness to Maori and Pacific Island people.

PMID- 14636390
TI  - Mental health service delivery to older people in New South Wales: perceptions of
      aged care, adult mental health and mental health services for older people.
AB  - OBJECTIVE: To compare the perceptions of aged care services, adult mental health
      services and mental health services for older people regarding aspects of mental
      health service delivery for older people in New South Wales, Australia. METHOD:
      The NSW Branch of the Faculty of Psychiatry of Old Age in association with the
      NSW Centre for Mental Health, sent a postal survey to all aged care services,
      adult mental health services and mental health services for older people in NSW.
      The survey canvassed issues ranging across service profiles, regional variations,
      availability of resources, processes of care, views on working relationships
      between services, difficulties and gaps experienced, and ways to improve co
      ordination and service delivery. Clinical issues such as the management and
      practice of psychiatric disorders of old age, educational/training requirements
      and skill and experience in working with older people were explored. RESULTS: An
      overall response rate of 86% was achieved, including 95% from aged care services
      (n = 58), 74% from adult mental health services (n = 62) and 90% from mental
      health services for older people (n = 20). Only 59% of aged care services and
      adult mental health services considered that their local mental health services
      for older people provided an adequate service; resource and budget limitations
      were portrayed as the main constraint. Mental health services for older people
      varied widely in structure, settings and activities undertaken. Access to mental
      health beds for older people was also variable, and alongside staffing levels was
      considered problematic. Lack of staff training and/or inexperience in
      psychogeriatrics posed a challenge for aged care services and adult mental health
      services. CONCLUSION: Relationships between aged care services, adult mental
      health services and mental health services for older people are affected by lack
      of access to psychogeriatric staff, resource limitations of mental health
      services for older people, and inadequate liaison and support between the service
      types. Joint case conferences, education, increased funding of mental health
      services for older people, and cross referrals were considered ways to address
      these issues.

PMID- 14636391
TI  - An international collaborative database: its use in predicting length of stay for
      inpatient treatment of anorexia nervosa.
AB  - OBJECTIVE: We describe the establishment of an Australasian multisite research
      database for inpatient treatment of anorexia nervosa (AN). Using this database,
      the second aim of this study is to investigate the extent to which length of stay
      (LOS) in participating facilities could be predicted at admission from patient,
      clinical, and site variables. METHOD: Standardized demographic and clinical data
      were collated for 213 admission episodes involving 154 participants over a 20
      month period from five Australian and one New Zealand specialist treatment
      centres. RESULTS: While nine variables significantly predicted LOS on univariate
      analysis, linear regression determined that only body mass index, and having had
      2-3 previous admissions made significant independent contributions to LOS.
      DISCUSSION: Multisite databases offer a viable means by which to conduct clinical
      research, particularly in regard to low prevalence disorders such as AN. Their
      additional advantage is that of involving front-line practitioners recruiting
      participants more likely to be representative of cases seen across treatment
      centres. At just under a fifth of the total variance predicted by the best-fit
      model, LOS in hospital remains an aspect of AN treatment difficult to predict,
      and future studies need to explore variables other than the obvious demographic
      or clinical issues at admission. The clinical and planning implications are
      discussed.

PMID- 14636392
TI  - A mother's attitude towards her infant and child behaviour five years later.
AB  - OBJECTIVE: The relationship between maternal attitude to the infant at 6 months
      of age and behavioural outcomes at 5 years is explored, controlling for numerous
      demographic, child and psychosocial family factors. METHOD: Data was used from
      the Mater-University Study of Pregnancy, an Australian longitudinal study of over
      7000 mothers and children followed from pregnancy to when the children were 5
      years. Measures ranging from the key variables of maternal attitude and child
      behaviour as well as numerous confounders were dichotomised. Logistic regression
      analyses were performed to examine the relationship between maternal negative
      attitude toward the infant and clinically significant levels of child behaviour
      problems and other infant risks, early social risks, and concurrent social risks.
      RESULTS: The results suggest that maternal negative attitude towards the infant
      at 6 months is an independent predictor of child behaviour problems at 5 years.
      This association remained significant for boys' externalizing behaviours and
      girls' internalizing behaviours. CONCLUSIONS: The findings lend support to the
      concept of a sensitive period in early infancy; the need for a broad perspective
      in the assessment of the mother-infant relationship and the need for early
      intervention with dysfunctional mother-infant dyads.

PMID- 14636393
TI  - Temperament, childhood environment and psychopathology as risk factors for
      avoidant and borderline personality disorders.
AB  - OBJECTIVE: To evaluate childhood experiences (neglect and abuse), temperament and
      childhood and adolescent psychopathology as risk factors for avoidant and
      borderline personality disorders in depressed outpatients. METHOD: One hundred
      and eighty depressed outpatients were evaluated for personality disorders. Risk
      factors of childhood abuse, parental care, temperament, conduct disorder
      symptoms, childhood and adolescent anxiety disorders, depressive episodes,
      hypomania and alcohol and drug dependence were obtained by questionnaires and
      interviews. RESULTS: Avoidant personality disorder can be conceptualized as
      arising from a combination of high harm avoidance (shy, anxious), childhood and
      adolescent anxiety disorders and parental neglect. Borderline personality
      disorder can be formulated as arising from a combination of childhood abuse
      and/or neglect, a borderline temperament (high novelty seeking and high harm
      avoidance), and childhood and adolescent depression, hypomania, conduct disorder
      and alcohol and drug dependence. CONCLUSIONS: Combinations of risk factors from
      the three domains of temperament, childhood experiences and childhood and
      adolescent psychopathology make major contributions to the development of
      avoidant and borderline personality disorders.

PMID- 14636394
TI  - Chronic posttraumatic stress disorder and family functioning of Vietnam veterans
      and their partners.
AB  - OBJECTIVE: This study examines the association between posttraumatic stress
      disorder (PTSD), in terms of the three main symptom clusters (intrusion,
      avoidance and arousal), and the self-report of family functioning of Vietnam
      veterans and the self-report of family functioning of their partners. A second
      objective was to determine if depression, anger and alcohol abuse mediated
      between PTSD symptoms and family functioning. METHOD: Vietnam veterans and their
      partners completed a series of questionnaires as part of their participation in
      the inpatient and outpatient PTSD treatment program, in the Veterans Psychiatry
      Unit, at the Austin and Repatriation Hospital. RESULTS: Data from 270 veterans
      and partners were used in the final analyses. The PTSD subscales were initially
      correlated with family functioning for veterans and family functioning for
      partners. Then two path diagrams were constructed and analyzed using the
      statistical program AMOS to test for mediating effects between PTSD symptoms and
      family functioning. For veterans there were significant initial correlations with
      all three subscales of the PTSD measure. In the path analysis when the mediating
      variables were included only the avoidance subscale of the PTSD measure remained
      directly associated with family functioning. The arousal PTSD subscale was
      mediated by anger. The measures of depression and anger were significantly
      associated with poor family functioning and the anger and the avoidance subscales
      were significantly associated with depression. In the second set of analyses
      conducted on data from partners, the PTSD symptoms of avoidance and arousal were
      initially correlated with family functioning. When the test for mediation was
      conducted none of the PTSD subscales remained associated with partners' self
      report of family functioning. Posttraumatic stress disorder arousal and alcohol
      abuse were mediated by anger for partners' self-report of family functioning.
      CONCLUSIONS: Posttraumatic stress disorder symptoms of avoidance for veterans,
      and comorbid symptoms of anger and depression for veterans, and anger on its own
      for partners appear to be important in the self-report of family functioning.
      These findings suggest that veterans and their partners have similar difficulties
      as couples with distressed relationships in the community.

PMID- 14636395
TI  - Extrapyramidal symptoms associated with quetiapine.

PMID- 14636396
TI  - Ventricular ectopics during crossover of atypical antipsychotics.

PMID- 14636397
TI  - First aid for a hypertensive crisis.

PMID- 14636398
TI  - Improvement in behaviour and attention in an autistic patient treated with
      ziprasidone.

PMID- 14636399
TI  - Citalopram-induced manic switch in an adolescent with epilepsy.

PMID- 14636400
TI  - Major depressive disorder and a past history of alcoholism.

PMID- 14636401
TI  - Serotonergic symptoms in neonates exposed to SSRIs during pregnancy.

PMID- 14636402
TI  - Generic services and early psychosis.

PMID- 14636413
TI  - The Nobel Prize in Chemistry for 2003.

PMID- 14636414
TI  - Prolegomenon for chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is a unique lymphoproliferative disorder that
      scarcely occurs under the age of 40; thereafter the incidence of CLL increases
      exponentially with age. CLL is characterized by progressive expansion of
      malignant CD5+ME+ B-cell clone accompanied by a myriad of cellular and humoral
      immune defects. Each of them might be linked to different clinically manifested
      complications such as increasing rate of infections, autoimmune disorders and
      disturbed immune surveillance against tumour cells. We assume that CLL occurs as
      a consequence of age-dependent, genetically related functional restrictions of
      the thymic microenvironment in supporting common lymphoid progenitor cells
      (CD5+ME+CD4-CD8-) to differentiate into mature T-cell and B-cell descendants. In
      conjunction with genetic abnormalities developing in B-cell progenitors,
      presumably expressing P glycoprotein (Pgp+), we postulate that developmentally
      altered T-cell descendants, along with quantitative imbalance among CD4+, their
      subsets and CD8+ lymphocytes in the peripheral blood, play an important
      additional role in facilitating the malignant B-cell clone emergence and in
      modulating the CLL clinical evolution. Namely, imbalance of any of T-cell
      mediated cell interactive homeostatic mechanisms accompanied by imbalance in the
      production of various cytokines might in CLL influence leukaemic B-cell growth by
      deregulating inducer (c-myc and p53) and/or suppressor (bcl-2 and mutant p53)
      oncogenes responsible for the promotion or suppression of B-cell mitogenesis that
      may in turn further contribute to their impaired differentiation and/or
      differentiation arrest. In conclusion, CLL might be interpreted as a primary
      immunodeficiency syndrome developing in elderly population due to gradually
      evolving restriction of genetically controlled programs in the thymic
      microenvironment responsible for irregular maturation of common lymphoid
      progenitor cells that constitutively express CD5 antigen and ME receptor into T
      cell and B-cell descendants.

PMID- 14636415
TI  - Kinetics of cytokine gene expression in human CD4+ and CD8+ T-lymphocyte subsets
      using quantitative real-time PCR.
AB  - The time kinetics of five cytokines [interleukin-2 (IL-2), IL-5, interferon-gamma
      (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour
      necrosis factor-alpha (TNF-alpha)] and one cytotoxic effector protein (granzyme
      B) was analysed by real-time quantitative polymerase chain reaction (PCR)
      following in vitro stimulation of human CD4 and CD8 T lymphocytes. Two stimuli
      were used, a mitogen [phytohemagglutinin (PHA)] and a recall antigen [purified
      protein derivative (PPD)]. The pattern of cytokine mRNA expression was found to
      be dependent on the T-cell subset and stimulus used. A wide interindividual
      variability in the cytokine gene expression pattern was demonstrated. Two
      expression patterns were observed. A bell-shaped expression profile was seen for
      most cytokines upon PHA activation in both subsets and PPD-activated CD4 T cells,
      whereas a biphasic/multiphasic expression pattern was noted in CD8 T cells upon
      PPD stimulation. For most cytokines, the time to induction was within 30 min of
      activation, and maximum accumulation seemed to be obtained after 4-8 h of
      activation. A sustained high level could, however, be noticed for up to 24 h.
      Granzyme B gene expression was also induced within 30 min of activation but
      showed a continuous gradual increase and late maximal accumulation (48-72 h). The
      findings of the present study are of importance when designing studies using the
      cytokine gene expression profile as a marker for antigen-specific T lymphocytes.
      It might be recommended that cytokine gene expression (IL-2, IL-5 and IFN-gamma)
      should be measured after 4-8 h of specific activation but also up to 24 h of
      stimulation is acceptable. Granzyme B should preferentially be measured after 48
      72 h of activation.

PMID- 14636416
TI  - Natural killer cell-mediated basal and interferon-enhanced cytotoxicity against
      liver cancer cells is significantly impaired under in vivo oxygen conditions.
AB  - Current immunostimulatory treatment protocols of cancer are often met with little
      success. Several lines of evidence indicate that the tumour microenvironment may
      impair the cytotoxic activity of natural killer (NK) cells. In this study, the NK
      cell-mediated killing of liver-derived cells was investigated at oxygen
      concentrations conform to those present in the human body at physiological and
      pathological conditions. The in vivo-relevant oxygen concentrations corresponding
      to 1, 2 and 6% were compared to those of the ambient air (21%) for their effect
      on the lysis of four liver-derived cell lines and the highly susceptible K562
      cells. Exposure to each of the hypoxic conditions had a significantly inhibitory
      effect on NK cytotoxicity. Treatment with interferon-alpha (IFN-alpha) in hypoxia
      enhanced the cytotoxic potential of the NK cells less than it enhanced the
      cytotoxicity at ambient oxygen conditions. In summary, the oxygen tension
      profoundly affects both the cytoxic activity of NK cells and their activation by
      IFN-alpha.

PMID- 14636417
TI  - Endotoxin tlerance inhibits lipopolysaccharide-initiated acute pulmonary
      inflammation and lung injury in rats by the mechanism of nuclear factor-kappaB.
AB  - In this study, the effect of endotoxin tolerance on lipopolysaccharide (LPS)
      initiated pulmonary inflammation, the local production of tumour necrosis factor
      alpha (TNF-alpha) and the cytokine-induced neutrophil attractant (CINC), as well
      as the activation of nuclear factor-kappaB (NF-kappaB) and its subunit
      composition, were examined in vivo. Endotoxin tolerance was reproduced by four
      consecutive daily intraperitoneal injections of 0.6 mg/kg of Escherichia coli
      055:B5 LPS. Compared with control rats, endotoxin-tolerant rats failed to
      increase the permeability of pulmonary microvascular or recruit neutrophil to
      lung tissue upon restimulation with 6 mg/kg of LPSs. Pretreatment with LPSs
      inhibited the protein level of TNF-alpha in bronchoalveolar lavage fluid (BALF)
      and mRNA expression of CINC in lung tissue in response to subsequent LPS
      stimulation. These changes were accompanied by the suppression of activation of
      NF-kappaB, including the low level of total amount of DNA-binding activity and
      high percentage of non-transactive p50 homodimers. These data demonstrate that
      endotoxin tolerance can alleviate the LPS-induced acute neutrophilic pulmonary
      inflammation in rats and can inhibit the proinflammatory cytokines in lung and
      suggest that endotoxin tolerance might result from the unresponsiveness of NF
      kappaB and persistent high percentage of p50 homodimers. Therefore, the
      phenomenon of endotoxin tolerance might be used as a strategy for the prevention
      or treatment of LPS-associated acute respiratory distress syndrome in which
      excessive or dysregulated inflammation leads to acute lung injury.

PMID- 14636418
TI  - Normal development of the gut-associated lymphoid tissue except Peyer's patch in
      MyD88-deficient mice.
AB  - MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and
      the response to gut commensal microbes. To investigate the role of TLRs/MyD88
      pathway in the development of the gut-associated lymphoid tissue (GALT), we
      examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also
      one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/
      and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed.
      However, PPs in 2-week-old MyD88-/- mice were significantly smaller than those in
      MyD88+/- mice. Also, in 2-week-old TLR4-/-, but not TLR2-/- mice, PPs did not
      develop rapidly. The development of PPs in MyD88-/- and TLR4-/- mice was
      completely recovered in 10 weeks. PP cells from MyD88-/- mice showed significant
      decrease in proliferation when stimulated with lipopolysaccharide. The
      development of CP and IEL was also normal in 10-week-old MyD88-/- mice. These
      results suggest that the TLRs/MyD88 pathway might be involved in the development
      of PPs only at early postnatal stage, and TLRs/MyD88-independent signalling is
      critically involved in the development of GALT in adult mice.

PMID- 14636419
TI  - Interferon-gamma tempers the expression of carcinoembryonic antigen family
      molecules in human colon cells: a possible role in innate mucosal defence.
AB  - Four carcinoembryonic antigen-related cell adhesion molecule (CEACAM)s, i.e. CEA,
      CEACAM1, CEACAM6 and CEACAM7, are localized to the apical glycocalyx of normal
      colonic epithelium and have been suggested to play a role in innate immunity. The
      expression of these molecules in colon carcinoma cells was studied at the mRNA
      and protein levels after treatment with interferon-gamma (IFN-gamma), interleukin
      1beta, live bacteria or lipopolysaccharide. The colon carcinoma cell lines LS174T
      and HT-29 were studied in detail using real-time quantitative reverse
      transcriptase-polymerase chain reaction, immunoflow cytometry and immunoelectron
      microscopy. IFN-gamma, but not the other agents, modified expression of CEA,
      CEACAM1 and CEACAM6. None of the agents upregulated CEACAM7 expression. Two
      expression patterns were seen. HT-29 cells, which initially showed low quantities
      of mRNAs and proteins, displayed marked upregulation of both mRNAs and proteins.
      LS174T cells transcribed stable high levels of mRNA before and after treatment.
      Additionally, IFN-gamma induced increased cell surface expression of CEA, CEACAM1
      and CECAM6. IFN-gamma has two important effects on the expression levels of the
      CEA family molecules in colon epithelial cells: direct upregulation of CEACAM1
      and promotion of cell differentiation resulting in increased expression of CEA
      and CEACAM6 and decreased expression of CEACAM7.

PMID- 14636420
TI  - Development of immunoglobulin A in infancy and childhood.
AB  - Serum and salivary concentrations of immunoglobulin A1 (IgA1) and IgA2 were
      studied in 105 Icelandic children aged 0-12 years. Serum concentrations of both
      IgA1 and IgA2 increased slightly (P < 0.001) during childhood. The salivary
      IgA1/IgA2 ratio tended to decrease during the same period; this trend is less
      apparent when omitting the youngest children. The salivary IgA1 and IgA2 output
      could be high, even in children with low levels of serum IgA. Only polymeric IgA
      was found in whole saliva. Interestingly, in serum, most IgA1 and IgA2 were
      polymeric during infancy. The proportion of polymeric IgA decreased, when the
      concentration of IgA increased. The polymeric form of IgA might provide the
      infant with better protection against invading microorganisms by activation of
      the innate immune mechanisms.

PMID- 14636421
TI  - Semiquantitative evaluation of mRNAs for the membranous form of immunoglobulin
      heavy chain is useful for investigating the etiology in CVID.
AB  - Common variable immunodeficiency (CVID) is a primary antibody deficiency syndrome
      characterized by defective B-cell maturation and antibody formation resulting in
      low serum antibody levels of all immunoglobulin (Ig) isotypes. To investigate the
      pathogenesis of CVID, we developed a set of competitive polymerase chain reaction
      for membrane-bound Ig heavy chain (mHC) mRNAs for IgM, IgG and IgA. Data on three
      children with CVID in group A of Bryant's classification were analysed. All the
      three mHC mRNA levels in Patient 1 were almost same as those in healthy controls.
      In Patient 2, mHC mRNA for IgM was detected at a level similar to that in
      controls, but mHC mRNAs for IgG and IgA heavy chains were not detected. In
      Patient 3, all the three mHC mRNAs were undetectable. Our data suggest that a
      different molecular basis exists in these patients with CVID even though all
      belong to group A of Bryant's classification. Use of our method facilitates a
      better understanding of molecular events in CVID patients and may be useful for
      precise classifications of CVID.

PMID- 14636422
TI  - Phenotypic features of peripheral blood leucocytes during early stages of human
      infection with Trypanosoma cruzi.
AB  - We performed a cross-sectional flow cytometric analysis of peripheral blood
      mononuclear cells to evaluate human immunologic status during early stages of
      Trypanosoma cruzi infection in children. We identified major immunological
      features corresponding to three proposed phases of disease: early acute (EA)
      phase, late acute (LA) phase and recent chronic (RC) phase. EA phase was
      accompanied by expansion of conventional B cells, up-regulation of CD54 on
      monocytes and down-regulation of CD54 on T cells and not associated with monocyte
      activation phenotypes or changes of natural killer (NK) population. LA phase was
      characterized by a selective increase in a distinct lineage of NK cells
      (CD16+CD56-), as well as a persistent expansion of B cells and down-regulation of
      CD54 on T cells. RC phase showed persistent low levels of CD54 molecule on T
      cells and an increase of B cells, mainly triggered by expansion of the B1-cell
      subset, as well as increased expression of human leucocyte antigen (HLA-DR) by
      monocytes. These findings reinforce the hypothesis that T. cruzi-derived antigens
      are able to activate NK cells before the development of T-cell-mediated immunity.
      Moreover, our data support previous findings of increased levels of B1
      lymphocytes during human Chagas' disease and show that this event is already
      present during initial stages of chronic infection.

PMID- 14636423
TI  - Elevated serum heat-shock protein 70 levels in patients with acute infection: use
      of an optimized enzyme-linked immunosorbent assay.
AB  - Heat-shock proteins (Hsps) are highly conserved throughout evolution and evoke
      great interest both in basic biology and in medicine. They are expressed in small
      quantities under normal conditions, and their expression can be strongly induced
      by several stressors. Although their action is basically intracellular, it is now
      obvious that these proteins can be released into the extracellular environment
      from viable cells. In this study, the human Hsp 70 serum concentrations were
      determined using an optimized, cost-effective enzyme-linked immunosorbent assay
      (ELISA). The average intra-assay variation was 6%, whereas the average interassay
      variation was 9%. The sensitivity of the assay was 10 ng/ml, and spiking
      experiments showed recoveries between 101 and 109%. As an application of the
      technique, we have investigated the serum levels of human Hsp 70 in patients with
      infection and in healthy subjects. Our data show significantly higher levels of
      Hsp 70 (P = 0.003) in patients compared to control subjects. Positive
      correlations were noticed between the serum levels of Hsp 70 and various markers
      of inflammation (IL-6; r = 0.579, P = 0.009, TNF-alpha; r = 0.552, P = 0.012, IL
      10; r = 0.361, P = 0.002). We conclude that Hsp 70 is involved in inflammation of
      infectious origin. The interindividual variation in the serum concentration of
      Hsp 70 precludes the use of serum Hsp 70 levels to distinguish patients from
      healthy subjects.

PMID- 14636424
TI  - Two doses of daclizumab in conjunction with low-dose cyclosporine, mycophenolate
      mofetil and steroids resulted in a low incidence of acute rejection after renal
      transplantation.
AB  - Five doses of daclizumab, given initially after kidney transplantation, reduce
      the rate of acute rejection (AR). Without cyclosporin A (CsA), a protocol,
      including daclizumab, mycophenolate mofetil (MMF) and corticosteroids (CSs), has
      recently shown efficacy in terms of graft function and survival. The rate of AR
      was relatively high, however. In this single-centre study, a CsA low-dose regimen
      was combined with two doses of daclizumab (1 mg/kg day 0 and 14), plus MMF (2 g)
      and CS. Forty-three cadaver donor renal recipients were included. Following the
      onset of graft function, target trough levels of CsA were 150-200 ng/ml for 90
      days, then 100-150 ng/ml. One year AR rate was 23% (n = 10) and events occurred
      at a median of 2.9 months (range from 9 days to 9.6 months). Delayed graft
      function (DGF) (absent spontaneous reduction of serum creatinine day 1) was 51%.
      Graft survival was 95% and patient survival 98% after 1 year. With respect to our
      previous experience, we used CsA, azathioprine and CSs (n = 223) from 1988 to
      1995, and the rate of AR was 57%. From 1996 to 1998, standard CsA doses, MMF and
      CS (n = 67) resulted in 31% AR. Median time to AR was 0.8 and 1.0 month, and the
      rate of DGF was 20 and 22%, respectively. This CsA low-dose protocol, including
      two doses of daclizumab, MMF and CS, resulted in a reduction and delay of AR
      episodes and excellent graft function, graft survival and patient survival,
      despite an increase in DGF.

PMID- 14636425
TI  - CCN5 modulates the antiproliferative effect of heparin and regulates cell
      motility in vascular smooth muscle cells.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) hyperplasia plays an important
      role in both chronic and acute vascular pathologies including atherosclerosis and
      restenosis. Considerable work has focused on the mechanisms regulating VSMC
      proliferation and motility. Earlier work in our lab revealed a novel growth
      arrest-specific (gas) gene induced in VSMC exposed to the antiproliferative agent
      heparin. This gene is a member of the CCN family and has been given the name
      CCN5. The objective of the present study is to elucidate the function of CCN5
      protein and to explore its mechanism of action in VSMC. RESULTS: Using RNA
      interference (RNAi), we first demonstrate that CCN5 is required for the
      antiproliferative effect of heparin in VSMC. We also use this gene knockdown
      approach to show that CCN5 is an important negative regulator of motility. To
      explore the mechanism of action of CCN5 on VSMC motility, we use RNAi to
      demonstrate that knock down of CCN5 up regulates expression of matrix
      metalloproteinase-2 (MMP-2), an important stimulator of motility in VSMC. In
      addition, forced expression of CCN5 via adenovirus results in reduced MMP-2
      activity, this also corroborates the gene knock down results. Finally, we show
      that loss of CCN5 expression in VSMC causes changes in VSMC morphology and
      cytoskeletal organization, including a reduction in the amount and macromolecular
      assembly of smooth muscle cell alpha-actin. CONCLUSIONS: This work provides
      important new insights into the regulation of smooth muscle cell proliferation
      and motility by CCN5 and may aid the development of therapies for vascular
      diseases.

PMID- 14636426
TI  - Surrogate end points of quality of life assessment: have we really found what we
      are looking for?
AB  - Outcome research is a new interesting field in medical research. Some years ago,
      a document of the American Society of Clinical Oncology distinguished the
      outcomes of a treatment into patient-outcomes (overall survival and quality of
      life) and cancer-outcomes (response rate), giving higher priority to patient
      outcomes. This document is one of the best structured instruments to evaluate and
      classify the outcomes in clinical oncology. Nevertheless, although overall
      survival and quality of life represent the main patient outcomes in clinical
      oncology, in the last years many researchers tried to overcome these
      recommendations, creating new surrogate end points to assess overall survival and
      quality of life. Surrogate end points can be useful tools when they are used to
      achieve preliminary data that anticipate the evaluation of the final outcome, but
      the use of surrogate end points instead of the main outcomes is quite dangerous,
      as it can provide wrong answers to clinical questions. The use (or abuse) of
      surrogate end points of quality of life has recently favoured some questionable
      decisions of the main regulator organs, such as the approval by the Food and
      Drugs Administration of the use of gemcitabine in advanced chemotherapy-naive
      pancreatic cancer, or mitoxantrone in the palliative treatment of hormone
      resistant pancreatic cancer, based on the improvement in clinical benefit (a non
      validated instrument to evaluate the outcome of palliative chemotherapy) besides
      a minimal and questionable overall survival, or pain control (evaluated with a
      non-validated instrument). A correct use of surrogate end points of quality of
      life within and not instead of quality of life assessment should be the
      engagement of our further efforts in quality of life research.

PMID- 14636427
TI  - Quality of life in multiple sclerosis: translation in French Canadian of the
      MSQoL-54.
AB  - BACKGROUND: Multiple Sclerosis (MS) is a neurodegenerative disease which runs its
      course for the remainder of the patient's life frequently causing disability of
      varying degrees. Negative effects on Health-related quality of life (HRQOL) are
      well documented and a subject of clinical study. The Multiple Sclerosis QOL 54
      (MSQOL-54) questionnaire was developed to measure HRQOL in patients with MS. It
      is composed of 54 items, and is a combination of the SF-36 and 18 disease
      specific items. OBJECTIVE: The objective of this project was to translate the
      MSQOL-54 into French Canadian, and to make it available to the Canadian
      scientific community for clinical research and clinical practice. METHODS: Across
      all French speaking regions, there are occurrences of variation. They include the
      pronunciation, sentence structure, and the lexicon, where the differences are
      most marked. For this reason, it was decided to translate the US original MSQOL
      54 into French Canadian instead of adapting the existing French version. The SF
      36 has been previously validated and published in French Canadian, therefore the
      translation work was performed solely on the 18 MS specific items. The
      translation followed an internationally accepted methodology into 3 steps:
      forward translation, backward translation, and patients' cognitive debriefing.
      RESULTS: Instructions and Items 38, 43, 45 and 49 were the most debated.
      Problematic issues mainly resided in the field of semantics. Patients' testing (n
      = 5) did not reveal conceptual problems. The questionnaire was well accepted,
      with an average time for completion of 19 minutes. CONCLUSION: The French
      Canadian MSQOL-54 is now available to the Canadian scientific community and will
      be a useful tool for health-care providers to assess HRQOL of patients with MS as
      a routine part of clinical practice. The next step in the cultural adaptation of
      the MSQOL-54 in French Canadian will be the evaluation of its psychometric
      properties.

PMID- 14636428
TI  - Ducks might quack.... children and domestic violence in rural areas.

PMID- 14636429
TI  - Differences and similarities between mothers' and fathers' experiences of
      parenting a child with a disability.
AB  - This qualitative study used focus groups to identify the differences and
      similarities in the experiences of parents of children with a disability. Two
      main themes emerged, showing the ways in which the mothers and fathers are alike
      or different. One concerns roles, actual and expected, in the various subsystems
      of family life. The other concerns the normalization and stigmatization that
      arise because of the child's problem. Mothers tend to score better in terms of
      interpersonal and group communications. It would seem that the fathers'
      expectations are harder to fulfil than the mothers'. The fathers' expectations
      are attuned to the outer world; the actual day-to-day tasks related to the
      child's care are not their priority. The mothers are less demanding and their
      expectations are more self-focused. Interestingly, these families are similar to
      families of children without a disability; however, the difficulties they
      experience are accentuated by the presence of a child with a problem.

PMID- 14636430
TI  - Changing practice in invasive procedures: the experience of the Krishnan Chandran
      children's centre.
AB  - The UK government's clinical governance strategy places emphasis on the provision
      of evidence-based, effective and client-focused care. This provided the framework
      for developing nurse-led venepuncture and immunization clinics. Evidence from
      research and examples of good practice were used to guide the structure and ethos
      of the new service. The professional development required to train one staff
      member in venepuncture and immunization techniques was adapted from already
      existing training. A specific training package was then developed to facilitate
      professional development of further staff. Audit was used, both to identify the
      need for the service and to assess its quality and cost-effectiveness. Consumer
      views were obtained through informal discussion and interviews with parents. This
      article explores how the concepts of clinical governance, together with the
      commitment of the multi-professional team, have resulted in a transformation of
      care for children undergoing invasive procedures in the outpatient department.

PMID- 14636431
TI  - Planning a career as a children's nurse: the availability of career guidance
      during the nurse diploma course.
AB  - The recruitment and retention of registered children's nurses is paramount to the
      implementation of the national service framework for children's services. In
      recent years there have been increased career opportunities for children's nurses
      and a diversity of career pathways. Career guidance has a potential contribution
      to make to the effective management of nurses' careers. This article presents
      findings on child health diplomates' experiences of career guidance during the
      nurse diploma course. Findings indicate a substantial unmet demand for career
      guidance. The implications of the findings for child health nurses' careers are
      discussed and considered in relation to two key questions: should efforts be
      directed towards ensuring greater provision of career guidance, and if so, by
      whom?

PMID- 14636432
TI  - Drug errors: what role do nurses and pharmacists have in minimizing the risk?
AB  - A multi-professional project was carried out in order to identify the
      interventions that nurses and pharmacists make in relation to drug administration
      (an intervention refers to 'the process of querying a prescription with a
      prescriber'). The project highlights the importance of both these occupational
      groups in identifying prescribing errors and preventing them from being
      translated into actual medication errors. It also identifies the need for
      adequate training for nursing and medical staff, along with system changes, in
      order to minimize the risk of medication errors.

PMID- 14636433
TI  - Mothers' experiences of their child's recovery in hospital and at home: a
      qualitative investigation.
AB  - Decreasing hospital stays, increasing day surgery and the assumption that parents
      will manage their child at home necessitate research into children's recovery.
      Given the scarcity of studies seeking parents' perspectives, this exploratory and
      interpretive study is timely, presenting a detailed account of mothers'
      experiences of managing their child's recovery in hospital and at home. The study
      supports the view that recovery begins not with discharge, but with admission and
      before, as hospital experiences directly shape the recovery process. Mothers'
      experiences of hospital's recovery enablers and inhibitors suggest that good
      recovery practices and policies remain erratic. Following discharge, parents help
      the child 'back to normal' by 'reading the recovering child' and balancing the
      child's desire for activity with the need for caution and safety. Developing a
      deeper understanding of parents' recovery experiences and perceptions would help
      nurses to form an empathic 'grounding' upon which to base improvements in
      children's recovery care.

PMID- 14636434
TI  - [Abstinence: the best way to control alcoholic liver diseases].

PMID- 14636435
TI  - [An epidemiological survey of alcoholic liver disease in Zhejiang province].
AB  - OBJECTIVE: To describe the brief survey of alcohol intake and the incidence of
      alcohol liver disease in Zhejiang province. METHODS: 18,237 requested persons
      aged over 18 years were selected by multi-stage stratified cluster sampling in
      Zhejiang province. Questionnaire about alcohol consumption, hepatic ultrasonic
      scan and detection of hepatic enzymes and markers of HBV and HCV were carried
      out. Daily alcohol intake more than 40g (including equal to 40g/d) was essential
      for the diagnosis of alcoholic liver disease. RESULTS: Among the 18,237 persons
      (male 12,042, female 6195), the average daily alcohol intake was (17.7 +/- 27.2)
      g. The incidence of alcoholic liver disease in Zhejiang province was 4.34% (male
      6.36%, female 0.36%) in the whole population. Four subtypes were separated as
      alcoholic cirrhosis, alcoholic fat liver, alcoholic hepatitis and mild alcoholic
      injury in liver with the corresponding incidence of 0.68%, 0.94%, 1.51% and 1.21%
      separately. CONCLUSION: Alcoholic liver disease is found to be a common disease
      in Zhejiang province, indicating an urgent need for the public education on
      alcohol abuse and the treatment on related health problems

PMID- 14636436
TI  - [Effects of Erk signal transduction on the cell cycle of rat hepatic stellate
      cells stimulated by acetaldehyde].
AB  - OBJECTIVE: To investigate the effect of PD98059 on the proliferation and cell
      cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore
      its mechanism. METHODS: Rat HSCs stimulated by acetaldehyde were incubated with
      different concentrations of PD98059. Cell proliferation was assessed by MTT
      colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin
      D1 and CDK4 were examined by RT-PCR. RESULTS: 20, 50, 100 micromol/L PD98059
      could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde
      in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs
      0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs
      stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3%
      and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059
      could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by
      acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and
      CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406,
      P<0.05). CONCLUSION: The Erk signal transduction pathway plays an important role
      in regulating the proliferation and cell cycle of rat hepatic stellate cells
      stimulated by acetaldehyde, which may be partly related to its regulative effect
      on the expression of cyclin D1 gene and CDK4 gene

PMID- 14636437
TI  - [Relationship between ALDH gene polymorphism and alcoholic liver diseases].
AB  - OBJECTIVE: To study the relationship between aldehyde dehydrogenase (ALDH) gene
      polymorphism and alcoholic liver disease, and investigate the genetic
      pathogenesis of alcoholic liver disease (ALD). METHODS: PCR, restriction
      endonuclease and electrophoresis were used, to detect the genotypes and alleles
      frequencies of ALDH gene in patients in the control group, alcohol dependent
      group and ALD group, and each group contained 20 patients. RESULTS: The
      frequencies of ALDH2*1 and ALDH2*2 allele had statistic significance between
      control group and ALD group (x2=4.80, P<0.05), and no statistic significance
      between control group and alcohol dependent group. ALDH2*1/*1 was predominant in
      alcohol dependent group and ALD group, while ALDH2*2/*2 was not detected.
      CONCLUSIONS: The gene polymorphism of ALDH is close to ALD. The allele of ALDH2*2
      may be a negative risk factor for the developing of ALD

PMID- 14636438
TI  - [Effects of N-acetylcysteine on serum IL-18 level in severe hepatitis patients].

PMID- 14636439
TI  - [Effects of Chinese herbal compound on the expression of hepatocyte cytochrome
      P450IIE1 in rats with alcoholic fatty liver].
AB  - OBJECTIVE: To study the effect of Chinese herbal compound (CHC) on the expression
      of hepatocyte cytochrome P450IIE1 in rat model of alcoholic fatty liver (AFL).
      METHODS: The AFL rats models were established by administering the drinking water
      with 40%(v/v) ethanol, and the changes of pathology in liver and hepatocyte
      P450IIE1 expression, as well as the contents of malondialdehyde (MDA), superoxide
      dismutase (SOD), glutathione (GSH), vitamin E (VitE) in liver were detected and
      compared with those in the control group. RESULTS: Fatty degeneration in liver
      recovered normally in the CHC-treated group. Immunohistochemical and in situ
      hybridization examination showed that CHC could inhibit the hepatocyte cytochrome
      P450IIE1 expression markedly, and restore the contents of MDA, SOD, GSH, VitE to
      nearly normal range. CONCLUSION: CHC can prevent AFL through inhibiting the
      hepatocyte cytochrome P450IIE1 expression markedly

PMID- 14636440
TI  - [Gene expression of interstitial collagenase MMP-13 in progressive phase of rat
      liver fibrosis induced by ethanol].
AB  - OBJECTIVES: To demonstrate the gene expression of MMP-13 in the progressive phase
      of ethanol-induced experimental liver fibrosis in rats. METHODS: 34 SD rats were
      randomized into two groups. The rats in experimental group (n=24) were given
      ethanol (44%, 7g/kg) every day, and the rats in control group (n=10) were given
      equality normal saline. Liver samples were harvested from experimental rats at
      the 4th, 12th and 24th weeks respectively. The dynamic expression of MMP-13 mRNA
      was assayed by semi-quantity reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: In normal rat liver, a faint band of MMP-13 mRNA was observed by
      RT-PCR (0.24+/-0.41). The gene expression of MMP-13 increased in the livers of
      rats treated with ethanol for 4 weeks (0.62+/-0.54), but it was not considered
      statistically, when compared with that in normal rats livers. And the livers from
      12-week-treated rats showed a markedly MMP-13 mRNA expression (1.65+/-0.47, t=
      4.363, P<0.01). Once the fibrosis became prominent (24 weeks), a faint band of
      MMP-13 mRNA was observed (0.39+/-0.25). CONCLUSION: MMP-13 participates in the
      degradation of newly-formed matrix in the early phase of rat liver fibrosis
      induced by ethanol, but it expresses in a distinct time frame

PMID- 14636442
TI  - [Percutaneous transhepatic coronary vein occlusion to treat esophagogastric
      variceal hemorrhage].
AB  - OBJECTIVES: To observe the effects and safety of percutaneous transhepatic
      coronary vein occlusion under ultrasound type B and X-ray guiding to treat
      esophagogastric variceal hemorrhage in cirrhotic patients. METHODS: Eighteen
      cirrhotic patients suffering from esophagogastric variceal hemorrhage were
      treated with percutaneous transhepatic coronary vein occlusion under ultrasound
      type B and X-ray guiding. Among them, 8 patients were treated during emergency
      bleeding and another 10 patients after hemorrhage. RESULTS: Seventeen patients
      were successfully treated with coronary vein occlusion. One patient rebled after
      6 hours of the treatment and was treated successfully with transjugular
      intrahepatic portosystemic shunt. The emergency hemostatic treatment efficacy was
      87.5%, and successful occlusion occurred in 94.4%. All patients were followed up
      for 1 to 24 months. There were 4 patients who suffered from rebleeding, 2
      patients from hepatic failure and 2 patients from hepatocellular carcinoma. There
      were 12 patients survived during the follow-up. CONCLUSION: Percutaneous
      transhepatic coronary vein occlusion under the type B ultrasonography and X-ray
      guiding is safe and efficient to treat esophagogastric variceal hemorrhage in
      cirrhotic patients

PMID- 14636441
TI  - [Protective effect of selective cyclooxygenase-2 inhibitor on alcohol-induced
      liver injury in rats].
AB  - OBJECTIVES: To investigate the effect of selective cyclooxygenase-2 (COX-2)
      inhibitor on alcohol-induced liver injury in rats. METHODS: 58 male Wistar rats
      were randomly divided into three groups: control group treated with dextrose and
      corn oil, model group with ethanol and corn oil, treatment group with corn oil
      and ethanol plus a selective COX-2 inhibitor celecoxib. All treatments were
      injected into stomach through intragastric tubes. Liver samples were analyzed for
      histopathology with light microscope (LM) and transmission electron microscope
      (TEM), and the expression of COX-2 with western blotting. Levels of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) in serum, levels of 6
      Keto-prostaglandin F1 alpha (6-k-PGF1a) and thromboxane B2 (TXB2) in liver, and
      activity of glutathione s-transferase (GST) both in liver tissue and in plasma
      were measured. RESULTS: LM and TEM indicated hepatocytes were injured obviously
      in the model group and slightly in the treatment group. The levels of AST and ALT
      in serum, TXB2 in liver and the activity of GST in plasma increased significantly
      in the model group (t> or =2.294, P<0.05), but the activity of GST in liver
      decreased significantly (t=8.856, P<0.01) compared with those in the control
      group. To compare with the model group, the levels of AST and TXB2 decreased
      significantly (t=4.305, P<0.01; t=2.799, P<0.01), meanwhile the activity of GST
      increased significantly (t=10.134, P<0.01) in the treatment group. COX-2
      expression in liver by western blotting increased significantly in the model
      group, compared with the control group (t=4.067, P<0.01) and the treatment group
      (t=2.251, P<0.05). Exceptionally, the level of 6-k-PGF1a decreased significantly
      (t=2.284, P<0.05) in the model group. CONCLUSION: COX-2 has involved in the
      alcohol-induced liver injury, and its inhibitor can diminish alcohol-induced
      liver injury in rats through decreasing TXB2 level

PMID- 14636443
TI  - [Expression of Bcl-2 and Bax proteins in rat liver fibrosis model and the role of
      IFN-gamma].
AB  - OBJECTIVE: To study the expression of Bcl-2 and Bax in rat liver fibrosis model
      induced by CCl4 and the role of IFN-gamma. METHODS: Liver fibrosis was induced in
      rats by subcutaneous injection of CCl4. The rats were divided into fibrosis model
      group, Bie-Jia-Ruan-Gan-Tablet treatment group and IFN-gamma treatment group (0.2
      MU.kg.d, i. m. for 12 weeks), and another 10 rats without any treatment were used
      as normal control. Bcl-2 and Bax proteins expression were detected by
      immunohistochemistry. RESULTS: Bcl-2 was expressed weakly in the homogenate of
      hepatocytes and hepatic sinusoid in normal control rats, and it was expressed
      stronger in fibrous septae, portal area, hepatic sinusoid, the homogenate and
      membrane of hepatocytes and central vein in fibrosis model rats (3.87%+/-2.37% vs
      9.46%+/-4.29%, t=2.83, P<0.05). Bax was expressed slightly in central vein and
      the hepatic sinusoid around, and it was expressed stronger in the homogenate of
      hepatocytes, hepatic sinusoid, fibrous septae, membrane of hepatocytes and
      epithelial cells of bile duct (3.50%+/-1.88% vs 9.80%+/-3.75%, t=3.72, P<0.01).
      Compared with that in fibrosis model rats, the expression of Bax was
      significantly lower in rats treated with IFN-gamma (9.80%+/-3.75% vs 5.85%+/
      2.35%, t=2.98, P<0.01), but the expression of Bcl-2 was not significantly
      different (t=1.49, P>0.05), however it was significantly lower in fibrous septae
      in IFN-gamma-treated group than in model group (6.58%+/-4.13% vs 9.46%+/-4.29%,
      t=2.80, P<0.05). CONCLUSION: The expression of Bcl-2 and Bax increases in liver
      fibrosis model rats, and IFN-gamma can promote myofibroblasts apoptosis

PMID- 14636444
TI  - [Differentiation of bone marrow stem cells in rat hepatic fibrogenesis
      environment].
AB  - OBJECTIVE: To observe the differentiation of bone marrow stem cells in rat
      hepatic fibrogenesis environment into hepatocytes. METHODS: Rat hepatic fibrosis
      was induced by subcutaneous injection of CCl4. Bone marrow stem cells with Thy
      positive, CD3 and CD45RA negative were enriched from the bone marrow by
      fluorescence-activated cell sorting. The bone marrow stem cells were labeled with
      PKH26-GL, and then autotransplanted. After six weeks, albumin, ck8 and a-smooth
      muscle actin expression were determined by immunocytochemistry. RESULTS: The
      PKH26-GL labeled cells expressed albumin and ck8, but did not express a-smooth
      muscle actin in hepatic fibrogenesis environment. CONCLUSION: Bone marrow stem
      cells in hepatic fibrogenesis environment can differentiate into hepatocytes, but
      can't differentiate into myofibroblasts

PMID- 14636445
TI  - [Cooperative anti-tumor effect of aspirin and TNF-related apoptosis-inducing
      ligand].
AB  - OBJECTIVE: To observe the anti-tumor effect of combination TNF-related apoptosis
      inducing ligand (TRAIL) with aspirin on liver cancer cell line, SMMC-7721.
      METHODS: The survival fraction of SMMC-7721 cells was measured by MTT assay,
      apoptosis rate and cell cycle was determined by flow cytometry, and the
      expression of apoptosis-related gene was identified by western blot. RESULTS: The
      survival fraction of SMMC-7721 cells treated with 300 ng/ml TRAIL, 3 mmol/L or 10
      mmol/L aspirin alone was 82.76%, 81.34% and 71.29% respectively, and the survival
      fractions of SMMC-7721 cells treated with TRAIL and 3 mmol/L or 10 mmol/L aspirin
      were 43.54% and 37.8% respectively. The apoptosis rates of SMMC-7721 cells
      induced by TRAIL and 3 mmol/L or 10 mmol/L aspirin were higher than that induced
      by TRAIL or aspirin alone (34.76% and 38.56% vs 21.25%, 1.89% and 6.08%), and
      G0/G1 arrest was observed under TRAIL and aspirin. The expression of Bcl-2 in
      SMMC-7721 cells treated by 3 mmol/L or 10 mmol/L aspirin decreased markedly, but
      no effect on Bax. CONCLUSION: The cooperative anti-tumor effect of aspirin and
      TRAIL may be related to the inhibition of the expression of Bcl-2 by aspirin

PMID- 14636446
TI  - [An epidemiological survey of subclinical hepatic encephalopathy].
AB  - OBJECTIVE: To investigate the prevalence and correlative factors of subclinical
      hepatic encephalopathy (SHE) in patients with cirrhosis in China by using
      psychometric tests with big sample size. METHODS: 409 patients with cirrhosis and
      416 patients with chronic hepatitis were investigated for the prevalence of SHE.
      In prevalence study questionnaire, psychometric tests (NCT and DST), laboratory
      data were used to estimate their liver function. RESULTS: According to age, the
      patients were divided into 5 groups (including<35, 35 to 44, 45 to 54, 55 to 64
      and >65 groups). There was highly statistical significance on the results of NCT
      and DST, between the cirrhosis patients and the controls (t> or =4.108, P<0.01).
      The prevalence of SHE in cirrhosis patients was 51.3%. Highly statistical
      significance was found (chi 2=23.910, P<0.01) among the Child-Pugh A, B, C groups
      (39.9%, 55.2% and 71.8%). According to age, gender, smoking, etiology and
      education, no statistical significance was found. Logistic regression showed that
      there was a close relationship between the SHE prevalence and the Child-Pugh
      score only, and no relationship had been found between the SHE prevalence and
      other factors including age, gender, smoking, etiology and education. CONCLUSION:
      The SHE prevalence in hepatic cirrhosis patients is 51.3%, and the Child-Pugh
      score may be an important risk factor

PMID- 14636447
TI  - [Influence of SEN virus infection on their response to lamivudine in patients
      with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the influence of SEN virus infection on their response
      to lamivudine in patients with chronic hepatitis B (CHB). METHODS: SEN virus-D
      and -H DNA were detected in 45 CHB patients who received lamivudine 12 months
      with nested-PCR, and YMDD motif mutations in HBV DNA were investigated with gene
      chip. RESULTS: The positive rate of SEN virus DNA was 11.1% (5/45), and there
      were four out of the five SEN virus DNA positive patients whose HBV DNA was
      positive, among them, two patients existed YMDD motif mutation. While ten out of
      the forty SEN virus DNA negative patients appeared HBV DNA positive. The response
      rate was significant lower in SEN virus-infected patients than that in uninfected
      patients (chi 2=3.97, P<0.05). CONCLUSION: Coinfection with SEN virus in chronic
      hepatitis B patients may adversely affect the outcome of treatment with
      lamivudine

PMID- 14636448
TI  - [Therapeutic effect of reduced glutathione on patients with alcoholic fatty
      liver].

PMID- 14636449
TI  - [Adverse effects of combining polyethylene glycol interferon with ribavilin on
      hepatitis C patients].

PMID- 14636450
TI  - [Distribution of HCV genotypes and its clinical features in patients coinfected
      with HCV and HBV].

PMID- 14636451
TI  - [Epidemiology of alcoholic liver diseases].

PMID- 14636452
TI  - [New insight on the pathogenesis of alcoholic liver diseases].

PMID- 14636453
TI  - [Diagnostic imaging of alcoholic liver diseases].

PMID- 14636454
TI  - [Alcoholic and non-alcoholic fatty liver diseases].

PMID- 14636455
TI  - [Invention of Kangxian Fufang I on the proliferation and collagen synthesis in
      cultured hepatic stellate cells stimulated by acetaldehyde].

PMID- 14636456
TI  - [Relationship between serum leptin and liver fibrosis in patients with alcoholic
      liver diseases].

PMID- 14636457
TI  - [Amplification of peripheral blood insulin-like growth factor II-mRNA and its
      clinical significance in the diagnosis of hepatocellular carcinoma].

PMID- 14636458
TI  - [Effects of oxymatrine on procollagen    metabolism and its gene expression in
      experimental fibrotic rats].

PMID- 14636459
TI  - [Relationship between gene polymorphism and both HBV and HCV infection].

PMID- 14636460
TI  - [The latest progresses of HBV infection models].

PMID- 14636461
TI  - [Current therapy strategies for alcoholic hepatitis].

PMID- 14636462
TI  - [The expression of nerve growth factor in inflammatory cells of induced sputum
      from patients with asthma].
AB  - OBJECTIVE: To investigate the expression of nerve growth factor (NGF) in
      inflammatory cells of induced sputum from patients with asthma. METHODS: Induced
      sputum samples were collected from 11 asthmatics in exacerbation, 19 asthmatics
      with stable disease and 11 healthy individuals. Sputum samples of 12 asthmatics
      with stable disease were collected again after treatment with inhaled
      corticosteroids (ICS) for 2 weeks. The differential counts of sputum inflammatory
      cells were studied. NGF was detected using immunocytochemistry and the positive
      percentages in different cells were measured. Interleukin-5 (IL-5) in sputum
      supernatants was detected using enzyme-linked immunosorbent assay. RESULTS: NGF
      was localized in the plasma of macrophages, lymphocytes and granulocytes. 1. In
      asthmatics with both exacerbation and stable disease, the NGF positive
      percentages in macrophages [(77.8 +/- 4.8)% and (68.1 +/- 5.3)%], lymphocytes
      [(43.2 +/- 9.3)% and (34.2 +/- 11.3)%], and granulocytes [(38.7 +/- 6.2)% and
      (32.1 +/- 3.7)%] were all significantly higher (P < 0.01) than those in the
      healthy controls [(37.6 +/- 8.4)%, (12.6 +/- 8.5)%, and (12.7 +/- 8.2)%,
      respectively]. The differences of those indices between patients with
      exacerbation and patients with stable disease were also significant (P < 0.01).
      Patients with exacerbation had significantly elevated levels of IL-5 [(124 +/-
      71) ng/L] compared with patients with stable disease [(52 +/- 23) ng/L] and the
      healthy controls [(26 +/- 12) ng/L] (P < 0.01). 2. In the 12 patients with stable
      disease evaluated after treatment with ICS, the NGF positive percentages in
      macrophages [(54.3 +/- 7.3)%], lymphocytes [(22.0 +/- 5.6)%], and granulocytes
      [(27.0 +/- 4.3)%], and the level of IL-5 [(29 +/- 13) ng/L] were all decreased
      significantly (P < 0.01) compared with the baselines [(67.0 +/- 5.0)%, (36.0 +/-
      9.0)%, (32.0 +/- 3.0)%, and (49 +/- 26) ng/L, respectively]. 3. The NGF positive
      percentages in both macrophages and granulocytes correlated to the sputum
      lymphocyte counts (r = 0.723, r = 0.630, P < 0.01; respectively) and the levels
      of IL-5 (r = 0.652, r = 0.636, P < 0.01; respectively). CONCLUSION: The
      expression of NGF in macrophages and lymphocytes in the airways is upregulated in
      asthma, which indicates a potential correlation between NGF and airway
      inflammation in asthma.

PMID- 14636463
TI  - [Enhanced expression of signal transducers and activators of transcription in
      lung tissue of hypoxic pulmonary hypertension rat models].
AB  - OBJECTIVE: To investigate the expression levels of signal transducers and
      activators of transcription (STATs) in the lung tissue of hypoxic pulmonary
      hypertension (HPH) rat models. METHODS: The Wister rat HPH models were divided
      into 4 groups: 1 week group (H1), 2 week group (H3), 3 week group (H3), and 4
      week group (H4) (n = 12 in each group). The levels of STATsmRNA expression of the
      lung tissue were measured by reverse transcription-polymerase chain reaction (RT
      PCR) and Northern blot. The protein expression of STATs and cellular morphologic
      changes were observed by immunohistochemistry and Tiger image analysis. RESULTS:
      The RT-PCR showed that the levels of STAT1mRNA expression of the lung tissue in
      H1 1.25 +/- 0.12, H2 2.28 +/- 0.15 and H3 1.27 +/- 0.12 were significantly higher
      than that in the healthy control group 0.61 +/- 0.07 (P < 0.01); the levels of
      STAT2mRNA expression in H1 0.54 +/- 0.06, H2 1.01 +/- 0.08 and H3 1.36 +/- 0.09
      were significantly higher than that in control group 0.30 +/- 0.03 (P < 0.01);
      the mRNA expressions of STAT3 in H1 0.74 +/- 0.11, H2 1.19 +/- 0.13 and H3 0.80
      +/- 0.08 were significantly higher than that in control group 0.26 +/- 0.10 (P <
      0.01); and the mRNA expressions of STAT5 in H1 0.92 +/- 0.10, H2 1.23 +/- 0.10
      and H3 1.03 +/- 0.11 were significantly higher than that in control group 0.60 +/
      0.11 (P < 0.01). The Northern blot assay demonstrated that the expressions of
      STAT1mRNA in H1 0.49 +/- 0.10 and H3 0.67 +/- 0.07 were significantly different
      from that in H2 0.91 +/- 0.07 (P < 0.01); the expressions of STAT3mRNA in H1 2.10
      +/- 0.21 and H3 2.58 +/- 0.17 were significantly different from that in H1 3.56
      +/- 0.29 (P < 0.01); the expressions of STAT5mRNA in H1 0.99 +/- 0.10 and H3 1.45
      +/- 0.12 were significantly different from that in H2 1.79 +/- 0.15 (P < 0.01).
      It is obvious that the mRNA expressions of STATs in the lung tissue of rat HPH
      models were increased in the 1st week, to the highest in the 2nd week, and
      decreased in the 3st week, and all higher than that of control group. The
      granules of STAT3 and STAT5, positively stained, were observed in the cytoplasm
      of pulmonary alveolar wall, intrapulmonary vascular and bronchial wall in H3. The
      protein expressions of STAT3 8.16 +/- 0.49 and STAT5 6.03 +/- 0.37 in H3 were
      markedly higher than those in H1, H4, and control group. CONCLUSION: The up
      regulation of the STATs expression in lung tissue of HPH rat models suggested
      that the STATs were involved in the pathogenesis of HPH formation.

PMID- 14636464
TI  - [A randomized, multicenter trial to compare the safety and efficacy of adenosine
      versus verapamil for termination of paroxysmal supraventricular tachycardia].
AB  - OBJECTIVE: To compare the safety and efficacy of intravenous adenosine with
      verapamil in terminating acute episodes of paroxysmal supraventricular
      tachycardia. METHODS: A randomized, multicenter trial to evaluate dose response
      in patients receiving adenosine and to compare the effects of adenosine with
      those of verapamil. A total of 122 patients with a tachycardia
      electrocardiographically consistent with paroxysmal supraventricular tachycardia
      were entered into the protocol. The adenosine group (n = 60) received sequential
      intravenous bolus doses of 3, 6, and 12 mg of adenosine to terminate PSVT and
      verapamil group (n = 62) were administrated 5mg or additional 5mg intravenously.
      Clinical variables and the time interval from the initiation of treatment to the
      termination of the supraventricular tachycardia, as well as the time from the
      initial effective dose of medication to the termination of supraventricular
      tachycardia were compared for adenosine and verapamil. RESULTS: There was no
      significant difference between the two groups with respect to clinical variables.
      Relative drug efficacies were 86.0% (52/60) for adenosine versus 87.1% (54/62)
      for verapamil, P = NS. The average time after injection to termination of
      tachycardia by adenosine was shorter than that of verapamil significantly [(34.2
      +/- 19.5) seconds vs. (414.4 +/- 191.2) seconds, P < 0.0001]. Adenosine caused
      adverse effects in 18.3% of patients, but they were transient and usually mild.
      CONCLUSIONS: Adenosine in graded doses up to 12 mg rapidly and effectively
      terminates acute episodes of paroxysmal supraventricular tachycardia. The overall
      efficacy of adenosine is similar to that of verapamil, but its onset of action is
      more rapid. Adverse reactions to adenosine are common but are minor and brief.

PMID- 14636465
TI  - [The effect of proton pump inhibitor on intragastric acidity and it relation to S
      mephenytoin hydroxylase genetic polymorphism].
AB  - OBJECTIVE: To study the effect of proton pump inhibitor rabeprazole (Rab) and
      omeprazole (Ome) on intragastric acidity and it relationship to S-mephenytoin
      hydroxylase (CYP2C19) genetic polymorphism. METHODS: Thirty duodenal ulcer
      patients were randomly divided into two groups. They were treated by the
      following strategies: Rab 10mg or Ome 20mg twice daily orally for two days.
      Intragastric pH over 24 hours was recorded from morning of the second day. Blood
      CYP2C19 genotyping of each patient was detected by PCR-restriction enzyme
      analysis. RESULTS: In Rab group, the mean intragastric pH values of the PM, hetEM
      and homEM were 6.3 +/- 0.1, 6.1 +/- 0.2, 6.0 +/- 0.1, no significant difference
      was observed among the three different genotype groups. In Ome group, they were
      6.3 +/- 0.1, 5.9 +/- 0.2, 5.6 +/- 0.3. The differences were significant (P <
      0.05). After treated with Rab for 24 hours, the mean and median 24 h intragastric
      pH values were significant higher than that of Ome (6.1 +/- 0.2, 6.1 +/- 0.3 vs
      5.8 +/- 0.4, 5.7 +/- 0.4, P < 0.05). The reason was that big difference existed
      in homEM type between Rab (6.0 +/- 0.1) than Ome (5.6 +/- 0.3) group. NAB
      occurred in 3 patients of each group. The sustaining time of NAB in Rab group was
      shorter than that of Ome group [(2.6 +/- 0.2) h vs (3.4 +/- 0.6) h]. CONCLUSIONS:
      The effect of Rab on control of intragastric pH was less affected by an
      individual's CYP2C19 status. Both Rab and Ome could not overcome NAB, but Rab
      could shorten the sustaining time of nocturnal acid breakthrough.

PMID- 14636466
TI  - [Continuous veno-venous hemofiltration in treatment of acute severe hyponatremia:
      a report of 6 cases].
AB  - OBJECTIVE: To investigate the effect of continuous veno-venous hemofiltration
      (CVVH) in the treatment of acute severe hyponatremia. METHODS: Six patients with
      acute severe hyponatremia were studied, including 5 males and 1 female, aged 48.5
      (25 - 61) years. Clinical manifestations of hyponatremia included confusion
      (6/6), drowsiness (3/6), and delirium (3/6). The course of hyponatremia before
      the initiation of CVVH was 45 - 48 hours. AN69, AV600, FH66 and HF1200
      hemofilters were applied and changed every 24 hours. The ultrafiltration rate was
      2 000 ml/h, with a blood flow rate of 200 - 250 ml/min, and the substitute fluid
      was infused by a pre-dilution route. Low molecular weight heparin was used for
      anticoagulation. RESULTS: The average treatment duration of CVVH was 59.7 (45.6 -
      86) hours. All the patients survived and tolerated CVVH well. During CVVH, the
      serum sodium increased significantly from (101.2 +/- 4.2) mmol/L before CVVH, to
      (115.0 +/- 2.7) mmol/L at the 6th hour of CVVH, (129.2 +/- 4.1) mmol/L at the
      24th hour, and (140.3 +/- 1.6) mmol/L at the 48th hour of CVVH; with the
      correction rate of serum sodium controlled at (2.5 +/- 0.4) mmol.L(-1).h(-1) over
      the first 24 hours, (1.2 +/- 0.1) mmol.L(-1).h(-1) for the first 48th hour, and
      the correction rate of (0.82 +/- 0.10) mmol.L(-1).h(-1). The sodium
      concentrations in the replacement solution were (16.0 +/- 6.0) mmol/L higher than
      the serum sodium concentration at 0 hour, (11.6 +/- 4.3) mmol/L higher at 4th
      hour, (5.5 +/- 5.1) mmol/L higher at 24th hour, and (0.75 +/- 0.96) mmol/L higher
      at 48th hour of CVVH. After CVVH, the serum osmolarity increased significantly,
      from (216.7 +/- 7.4) mOsm/kgH(2)O pre-CVVH, to (245.0 +/- 5.5) mOsm/kgH(2)O at
      6th hour, with a correction rate of (5.16 +/- 0.81) mOsm.kgH(2)O(-1).h(-1);
      (272.7 +/- 7.1) mOsm/kgH(2)O at 24th hour, with a correction rate of (2.33 +/-
      0.28) mOsm.kgH(2)O(-1).h(-1); and (295.0 +/- 4.2) mOsm/kgH(2)O at 48th hour, with
      a correction rate of (1.63 +/- 0.20) mOsm.kgH(2)O(-1).h(-1). The Glasgow scores
      and APACHEII scores improved significantly as compared to pretreatment.
      CONCLUSION: CVVH is effective in the treatment of acute severe hyponatremia, and
      could be considered as a treatment option because of its slow and continuous
      nature. A low-sodium replacement solution should be prepared to minimize its
      sodium concentration difference from the serum concentration. We recommend that
      the serum sodium concentration be corrected at an average rate of (2.50 +/- 0.14)
      mmol.L(-1).h(-1) at 6 h, (1.2 +/- 0.1) mmol.L(-1).h(-1) at 24 h and (0.82 +/-
      0.10) mmol.L(-1).h(-1) at 48 h.

PMID- 14636467
TI  - [Study on cardiac toxicity in acute promyelocyte leukemia treatment of arsenic
      trioxide intravenous infusion in general dose].
AB  - OBJECTIVE: To study the cardiac toxicity of arsenic trioxide (As(2)O(3)).
      METHODS: To investigate and analyze the probable mechanisms of cardiac toxicity
      of As(2)O(3) by dynamic monitoring of clinical manifestations, basal cardiac rate
      and electrocardiographic data of acute promyelocyte leukemia (APL) patients
      during As(2)O(3) therapy. The instant change of the action potential, the I(Ca-L)
      and I(k) of single cardiac myocyte of guinea pig was also observed with patch
      clamp dynamically. RESULTS: Approximately 71.4% of the 28 cases of APL showed
      cardiac toxic reaction in different degree in the first week after As(2)O(3)
      intravenous infusion in general dose, mainly expressing rapid heart rate or
      prolonged QT interval. As(2)O(3) could prolong the action potential duration from
      (563.0 +/- 55.8) ms to (737.7 +/- 131.7) ms (P < 0.05) and increased the I(Ca-L)
      and I(k) of single cardiac myocyte of guinea pig in vitro. CONCLUSION: As(2)O(3)
      intravenous infusion in general therapeutic dose can cause tachycardia and
      prolong QT interval in some of the APL patients. The probable mechanism of these
      side-effects may be due to instant involvement of ionic channel of cardiac
      myocyte.

PMID- 14636468
TI  - [An analysis of the causes of dementia in 383 elderly autopsied cases].
AB  - OBJECTIVE: To survey the causes of dementia confirmed by autopsy in the elderly
      and to have a better understanding of various causes of senile dementia. METHODS:
      A retrospective study on clinical and pathological diagnosis in 383 cases aged 60
      and over with autopsy performed was carried out clinical diagnosis of dementia
      was based on DSM-IVR, NINCDS-ADRDA and NINCDS-AIREN criteria. Gallyas-Braak
      staining, Tau and Ubiquitin Immunohistochemistry staining were adopted for
      diagnosing neurodegenerative dementia and distinguishing various degenerative
      diseases. RESULTS: Among the 383 aged cases with consecutive autopsy, 78 cases
      were found to have clinical features and brain pathologic change related to
      dementia. The incidence of dementia in the aged patients with autopsy was 20.4%.
      Of all the cases, vascular dementia accounted for 38.5% (30 cases), being the
      most frequently on countered. Next in order were degenerative dementias including
      Alzheimer's disease (11 cases) and non-Alzheimer's degenerative dementia (9
      cases) including dementia with Lewy bodies, corticobasal degeneration,
      progressive supranuclear palsy, Pick's disease and idiopathic Parkinson'disease.
      Degenerative dementias accounted for 25.6% (20 cases). Various medical disorders
      including hepatic encephalopathy, pulmonary encephalopathy, hypoglycemia with
      cognitive impairment were also relatively common, they accounted for 20.5% (16
      cases). The other less common causes included brain tumor, normal pressure
      hydrocephalus and subdural hematoma, 12 cases accounted 15.4%. The total
      accordance rate of clinical and pathologic diagnosis of senile dementia was
      64.5%, the accordance rates of medical disorders such as hepatic encephalopathy,
      pulmonary encephalopathy and brain metastatic tumors were all 100%, the
      accordance rate of vascular dementia and degenerative dementia was 66.7% and 40%
      respectively. CONCLUSION: Senile dementia is a clinical syndrome caused by
      multiple factors. Physician should think of various possible causes of dementia,
      basing on their clinical history and laboratory results. Promoting autopsy and
      adopting new pathological techniques would increase the diagnostic accuracy of
      degenerative dementia.

PMID- 14636469
TI  - [Fasting serum free fatty acid, insulin sensitivity index and serum lipid levels
      in individuals with different body mass index and glucose tolerance].
AB  - OBJECTIVE: To investigate the relationship among fasting serum free fatty acid
      (FFA), insulin sensitivity index (ISI), serum triglyceride (TG) and total
      cholesterol (TC) levels in subjects with different body mass index (BMI) and
      glucose tolerance by using Bergman's minimodel method. METHODS: 26 normal control
      subjects, 39 obese subjects, 25 impaired glucose tolerance (IGT) subjects and 21
      patients with newly diagnosed type 2 diabetes mellitus (DM) were recruited into
      this study. Serum FFA level was measured with radioimmunoassay and ISI was
      obtained by using Bergman's minimal model method. RESULTS: (1) In the four
      groups, serum FFA concentration of the control group was significantly lower than
      that of the other three groups, although there was no difference among the latter
      three. (2) ISI level of the control group was significantly higher than that of
      other three groups, while there was no difference among the latter three. (3)
      After adjusting with BMI, there was still significant difference in serum FFA
      levels between the control and the other three groups. (4) ISI, HOMAIR, BMI,
      waist hip ratio (WHR) and TG were all related to the concentration of serum FFA
      (r = -0.454, 0.213, 0.241, 0.336 and 0.414 respectively, P < 0.01, < 0.05, <
      0.05, < 0.01 and < 0.01 respectively), while age, sex and serum TC levels were
      not related with serum FFA. (5) According to multivariate stepwise regression,
      ISI, BMI and TG were the major determinant factors for FFA (R(2) = 0.109, 0.212,
      0.156, P < 0.001). CONCLUSIONS: Besides BMI, ISI and serum TG level are the major
      determinant factors that affect the concentration of serum FFA. As compared with
      the simple index HOMAIR, ISI level was more significantly related with serum FFA
      concentration. FFA levels are significantly different in various glucose tolerant
      states even after adjusting with BMI. FFA levels were obviously higher in
      subjects with IGT or type 2 diabetes mellitus.

PMID- 14636470
TI  - [The impact of selective cycloxygenase-2 inhibitor celexibo on the formation of
      cholesterol gallstone].
AB  - OBJECTIVE: To determine the effects of specific cyclooxygenase-2 (COX-2)
      inhibitor celexibo on the formation of gallstone in rabbits by comparing both the
      mucosa damage and the risk of gallstone formation. METHODS: 30 rabbits were
      equally divided into three groups: gallstone group (induced by high cholesterol
      diet HCD), celexibo group (treated with celexibo 10 mg.kg(-1).day(-1) in addition
      to HCD) and control group (fed with formal diet). After 7 weeks, bile was
      obtained for observing gallstone formation, and the morphologic changes of the
      mucosa were assessed under microscopy. The level of COX-2 in gallbladder mucosa
      in each group was estimated with immunohistochemical assay. RESULTS: Celexibo
      group had lower risk to get gallstones than gallstone group (2/10 vs 9/10, P <
      0.05). The degree of mucosa inflammation and level of COX-2 expression were
      significantly higher in gallstone group than in the other two groups (0.055 +/-
      0.006 vs 0.017 +/- 0.003, P < 0.001; 0.055 +/- 0.006 vs 0.169 +/- 0.001, P <
      0.001). CONCLUSIONS: Specific COX-2 inhibitor celexibo can decrease the risk of
      gallstone formation. COX-2 is highly expressed in gallbladder mucosa of
      gallstone, which suggests that there is certain inflammatory mechanism in the
      cholesterol gallstone formation.

PMID- 14636471
TI  - [The effects of 17 beta-estradiol on the expression of osteoprotegerin, the
      ligand of osteoprotegerin and related cytokines in osteosarcoma MG63 cells].
AB  - OBJECTIVE: To observe the regulative effects of 17 beta-estradiol (17 beta-E(2))
      and ICI 182780 on the expression of osteoprotegerin (OPG), the ligand of
      osteoprotegerin (OPGL) and the related cytokines [macrophage colony-stimulating
      factor (M-CSF), TRAIL and transforming growth factor beta(TGF beta)] in MG63
      cells. METHODS: The expression of OPG, OPGL, M-CSF, TRAIL and TGF beta mRNA was
      examined by reverse transcriptase (RT)-PCR. The expression of OPG and OPGL
      protein was measured with Western blot. RESULTS: (1) 17 beta-E(2) up-regulated
      the expression of OPG and TGF beta but down-regulated OPGL, M-CSF and TRAIL
      expression in MG63 cells. (2) ICI 182780 showed varied transactivating capability
      when regulating the expression of OPG, OPGL, TRAIL, M-CSF and TGF beta genes in
      MG63 cells. CONCLUSIONS: (1) One of the key pathogenetic factors of
      postmenopausal osteoporosis is that estrogen deficiency leads to the decreasing
      expression of OPG and TGF beta but the increasing expression of some bone
      resorbing cytokines such as OPGL, M-CSF and TRAIL in osteoblasts, then
      stimulation of osteoclast differentiation and activity which potentiates bone
      resorption and bone loss; (2) ICI 182780 shows partial transactivating activity
      in osteoblasts, so it should belong to a kind of selective estrogen receptor
      modulators.

PMID- 14636472
TI  - [The use of Juniper's asthma quality of life questionnaire in Chinese
      asthmatics].
AB  - OBJECTIVE: One of the most important objectives in the management of asthma is to
      improve the quality of life of patients. We summarized our experience in using
      Juniper's asthma quality of life questionnaire (AQLQ) in Chinese asthmatics.
      METHODS: Measurement instruments included self-administered AQLQ mandarin Chinese
      version and its standardized version. The data were from 210 AQLQ evaluations
      from 96 patients. RESULTS: AQLQ and its four domains weakly correlated with
      forced expiratory volume in 1 second (FEV(1)) except the environment domain (r:
      0.201 - 0.284). If the asthmatic patients were graded into 4 groups based on
      FEV(1), AQLQ and its four domains significantly detected the differences among
      the groups. The change of AQLQ, however, was not correlated with the change of
      FEV(1). The change of AQLQ domain of symptoms was correlated with the change of
      peak expiratory flow. CONCLUSION: The Juniper's AQLQ performs well in Chinese
      asthmatics. AQLQ is correlated with pulmonary function and probably more
      sensitive and accurate than pulmonary function in the evaluation of disease
      severity.

PMID- 14636473
TI  - Troponin in chagas disease.

PMID- 14636474
TI  - The use of molecular typing to evaluate the dissemination of antimicrobial
      resistance among Gram-negative rods in Brazilian hospitals.
AB  - Antimicrobial resistance has increased rapidly in Brazil and worldwide during the
      past few years, giving rise to a growing necessity for antimicrobial resistance
      surveillance programs. These programs have been instituted in order to monitor
      bacterial resistance in various regions, and to guide empirical antimicrobial
      therapy. We evaluated the use of molecular typing in multicenter surveillance
      programs. We also studied the dissemination modes of selected resistance
      profiles. Antimicrobial susceptibility to various antimicrobial agents was
      evaluated by the reference broth microdilution method. Bacterial isolates with
      selected susceptibility patterns were characterized by pulsed field-gel
      electrophoresis (PFGE). A total of 119 Gram-negative bacteria were molecularly
      typed, including 22 imipenem-resistant Pseudomonas aeruginosa, 26 ESBL-producing
      Escherichia coli, 27 cefoxitin-resistant-ESBL-producing Klebsiella pneumoniae, 33
      Enterobacter spp., 8 Citrobacter spp., and 3 S. marcescens isolates resistant to
      ceftazidime. The isolates were from clinically apparent bacteremia of patients
      hospitalized in medical centers located in 13 cities of 11 Brazilian states. Our
      molecular typing results revealed a great genetic diversity among isolates of the
      same species. However, some major PFGE patterns were found in more than one
      isolate. All repeated PFGE patterns were detected in only 2 isolates, which were
      isolated within the same institutions or in different medical centers. We
      conclude that the ability to characterize organisms phenotypically and
      genotypically is a powerful epidemiologic tool and it provides unique information
      that is very important for multicenter surveillance programs.

PMID- 14636475
TI  - Effect of pathogenic yeasts on human platelet aggregation.
AB  - We investigated the effects of Candida albicans, Cryptococcus neoformans and the
      respective culture supernatants on human platelet aggregation (PA). Both yeasts
      were unable to aggregate the platelets directly. On the other hand, cells of
      these yeasts significantly (P < 0.01) inhibited PA at concentrations equal to or
      higher than 1 x 10(6) cells/mL for C. albicans and equal to or higher than 1 x
      10(5) cells/mL for C. neoformans. When the supernatants of one-week broth
      cultures were added to the activated platelets no inhibition in aggregation was
      observed. Apparently somatic components of these yeasts, but not their metabolic
      products, exert an antagonistic effect on the aggregation of human platelets,
      possibly aiding the fungi in their evasion of the microbicidal defense system
      during vascular dissemination.

PMID- 14636476
TI  - Nosocomial infection in a pediatric intensive care unit in a developing country.
AB  - OBJECTIVE: Determine the rate and outcome of nosocomial infection (NI) in
      pediatric intensive care unit patients in a developing country. DESIGN:
      Prospective cohort study using the Centers for Disease Control and Prevention
      definitions to diagnose nosocomial infection and NNISS (National Nosocomial
      Infection Surveillance System) methodology. SETTING: Sao Paulo Hospital -
      Universidade Federal de Sao Paulo - Brazil, a 700-bed teaching hospital with an 8
      bed pediatric intensive care unit. PARTICIPANTS: All 515 children consecutively
      admitted to the pediatric intensive care unit from April 1996 to October 1997.
      RESULTS: The NI incidence was 18.3% and the mean infection rate per 1,000 patient
      days was 46.1; the ventilator-associated pneumonia rate was 18.7 per 1,000
      ventilator days; the central line-associated bloodstream infection rate was 10.2
      per 1,000 central line days; and the urinary tract catheter-associated infection
      rate was 1.8 per 1,000 catheter days. Pneumonia was the most common NI (31.6%),
      followed by bloodstream infections (17.3%), and surgical site infection (17.3%).
      Gram-negative bacterias were the most common pathogens identified in the NIs
      (54.8%), followed by Gram-positive bacterias (23.8%), and yeasts. CONCLUSION:
      Pneumonia was the most common type of NI. A high incidence of ventilator
      associated pneumonia and central line-associated bloodstream infections was
      found, whereas the urinary tract catheter-associated infection rate was low. Gram
      negative bacterias were the most common etiologic agents identified in the unit,
      and yeasts were frequently found. Pediatric patients have characteristics of
      their own, with major differences when compared to the adult population.

PMID- 14636477
TI  - Infection and colonization by Staphylococcus aureus in a high risk nursery of a
      Brazilian teaching hospital.
AB  - Neonates are susceptible to nosocomial infections due to immunological
      immaturity, prolonged hospital stay and the use of invasive procedures. We
      evaluated the incidence of infections and the prevalence of colonization by MRSA
      (Methicillin-resistant Staphylococcus aureus) and MSSA (Methilin-susceptible
      Staphylococcus aureus), as well as colonization risk factors. Staphylococcal
      infections were observed by analyzing medical records in the HICS (Hospital
      Infection Control Service) and the HRN (High Risk Nursery). Additionally, four
      inquiries concerning colonization prevalence were made for S. aureus, from
      January/2000 to December/2002. Clinical specimens from the nostrils, mouth and
      anus were cultivated in mannitol-salt agar plates and identification was made
      through standard methods. The frequency of neonates colonized by S. aureus was
      49%. MSSA was more prevalent (57%) than MRSA (43%). Risk factors related to the
      acquisition of MRSA were: low weight and antibiotic use., Hospital stay was the
      only variable significantly associated with colonization by S. aureus. The
      incidence of infections by S. aureus during the last three years was 2.18% (159
      cases). Nine of them (5.5%) were associated with MRSA and 150 (94.5%) with MSSA.
      Staphylococcal infections were considered as invasive (sepsis) and non-invasive
      (conjunctivitis, cutaneous), corresponding to 31% and 69%, respectively. The MRSA
      phenotype in infection was rare compared with methicillin-susceptible samples,
      although S. aureus, MRSA and MSSA colonization rates were high.

PMID- 14636478
TI  - Common infectious diseases and skin test anergy in children from an urban slum in
      northeast Brazil.
AB  - BACKGROUND: Acute respiratory infection (ARI), diarrheal disease (DD) and
      infective dermatitis (ID) are important causes of morbidity in children under
      five, in Northeast Brazil. OBJECTIVES: (a) to evaluate the morbidity of ARI, DD
      and ID; and (b) to determine their association with cellular immunity in poor
      urban children from Fortaleza, Brazil. MATERIALS AND METHODS: A prospective
      cohort study. At enrollment, multipuncture skin-tests (Multitest CMI) were
      performed and interpreted according to standard procedures. Children were
      followed for infectious diseases by weekly home visits. RESULTS: Seventy-one
      children aged 6 to 21 months were recruited in an ongoing cohort of newborns. A
      mean of 39 (6 to 63) home visits per child were made, which detected 184.5
      symptomatic days per child-year of observation. ARI was present in 62% of the
      days of illness (6,378 out of 10,221), DD in 23% (2,296 days), ID in 6% (597) and
      other infections in 4% (373). Episodes per child-year were: 10 for ARI, 7 for DD
      and 1 for ID. Twelve (17%) out of 71 children were anergic. The incidences of
      ARI, DD and ID were similar in responsive versus anergic children. The mean
      duration of ID in anergy was 8.5 days, while it was 4.3 in the responsive group
      (P=0.007). Anergy was independent of age, sex and nutritional status.
      CONCLUSIONS: A high incidence of ARI and DD was found in these poor urban
      children. Skin-test responsiveness was not related to malnutrition, nor to
      morbidity due to ARI and DD, however anergic children had a longer duration of
      infective dermatitis.

PMID- 14636479
TI  - Human herpesvirus-8 (HHV-8) antibodies in women from Sao Paulo, Brazil.
      Association with behavioral factors and Kaposi's sarcoma.
AB  - BACKGROUND: With the spread of AIDS, many HIV-infected women have been diagnosed
      with Kaposi's sarcoma (KS), especially in Africa. Since the discovery of a novel
      herpesvirus as the causative agent of KS (human herpesvirus 8 - HHV-8) several
      seroepidemiological studies have been conducted to identify groups at risk for
      KS. The risk for women in Brazil has not been studied. MATERIALS AND METHODS: We
      searched for HHV-8 antibodies in sera obtained from a bank made up of samples
      from 3 groups of individuals: Group I: 163 HIV-1-infected women attended at an
      ambulatory clinic in 1994; Group II: 108 children born to HIV-1-infected mothers
      from 1990 to 1992, their antibodies reflected maternal infection, and Group III:
      630 HIV-1-seronegative, healthy women. In-house immunofluorescence and Western
      Blot assays based on the BCBL-1 cell line were used to detect anti-latent and
      anti-lytic HHV-8 antibodies. RESULTS: Group I had an overall frequency of
      antibodies of 8.6%, with a 1.2% frequency of anti-latent antibodies and an 8.0%
      frequency of anti-lytic antibodies. Similar results were detected in Group II,
      i.e., no cases with anti-latent antibodies and a 7.4% frequency of anti-lytic
      antibodies. In contrast, prevalences of 1.1% anti-latent antibodies and 0.3% anti
      lytic antibodies were observed in Group III. CONCLUSIONS: The epidemiologic
      pattern of HHV-8 in women from Sao Paulo varies according to behavioral factors,
      with emphasis on the sexual and blood routes of virus transmission/acquisition.
      Although HHV-8 anti-lytic antibodies were found in HIV-1-infected women, no case
      of KS was detected. Protective factors against KS are probably related to gender
      and/or to antiretroviral therapies introduced in Brazil since 1994.

PMID- 14636480
TI  - Evaluation of techniques for the diagnosis of Strongyloides stercoralis in human
      immunodeficiency virus (HIV) positive and HIV negative individuals in the city of
      Itajai, Brazil.
AB  - Human immunodeficiency virus (HIV) and intestinal parasites are common in Brazil.
      Previous studies have shown that infection with Strongyloides stercoralis is
      frequently associated with HIV infection. Strongyloidiasis is difficult to
      diagnosis and stool examination with conventional techniques fails to detect the
      helminth larvae. We made a prospective study, to test the efficacy of the agar
      plate technique to detect S. stercoralis in 211 HIV-positive patients and 213 HIV
      negative patients in the city of Itajai, Brazil, between September 2001 and June
      2002. The feces samples of these patients were processed and analyzed according
      to the following methods: Lutz, formalin ethyl acetate, Baermann, Harada-Mori and
      agar plate culture. HIV-positive patients were more frequently infected by S.
      stercoralis (odds ratio= 5,.687). Among the methods used on fecal specimens, the
      larvae of S. stercoralis were most efficiently detected by the agar plate (69.7%)
      method, followed by the Baermann and the formalin ethyl acetate methods (48.5%)
      (P=0.01), Lutz (42.4%) (P=0.01), and Harada-Mori culture (24%) (P=0.001).
      Therefore agar plate culture is the most efficient method for the detection of S.
      stercoralis larvae and this technique should be the test of choice, especially in
      immunocompromised patients.

PMID- 14636481
TI  - Comparative study of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia
      Brazil.
AB  - Hepatitis C virus displays a high degree of genetic mutation, with considerable
      heterogeneity, motivating clinical and biomolecular investigations. It is
      necessary to understand the effects of genotypes on the course of the disease, as
      well as their peculiarities at the regional level. OBJECTIVE: The study objective
      was to compare epidemiological, biochemical and histological aspects of hepatitis
      C virus genotypes 1 and 3 in Salvador, Bahia. STUDY DESIGN: Data were collected
      retrospectively from outpatient medical records. MATERIALS AND METHODS: 127
      patients with positive anti-HCV results were selected, based on detectable RNA
      HCV (RT-PCR) of genotypes 1a, 1b and 3a. RESULTS: Thirty-nine (30.7%) individuals
      were infected by subtype 1a, 45 (35.4%) by subtype 1b and 43 (33.9%) by subtype
      3a. Most (73.2%) patients were male, with an average age of 47.8 years. The
      subtype 1b-infected patients had the highest average age (512 +/-11.17; P=0.09).
      The use of illicit injected drugs was more frequent among subtype 3a infected
      individuals when compared with genotype 1 (6/43; 14% and 3/84; 3.6%,
      respectively; P=0,06). No significant differences were found for other
      epidemiological characteristics. Average values for GT, AST, ALT and ferritin did
      not differ between the groups (64, 78, 109, 276, respectively). Thyroid
      dysfunction occurred in 7/30 (23.3%) of those infected by genotype 3 (P=0.05).
      Cryoglobulinemia was also more frequent in this group (5/13, 38%, P=0.02). Most
      patients presented limited necro-inflammatory activity, stages 2 and 3 by the
      METAVIR Classification. In some cases, dissociation was noticed between
      inflammatory activity and fibrosis. No significant differences were found in the
      histopathological findings of the various genotypes. Younger patients had a
      significantly smaller degree of necrosis in stomatocytosis (P=0.032) and fibrosis
      (P=0.012). Intense parenchymatous activity and lymphoid follicles were more
      frequent among alcohol consumers (P=0.06 and P=0.04, respectively). CONCLUSIONS:
      In Bahia, genotype 3 dissemination seems to be associated with illicit drug use.
      The disease evolution depends on a function of complex interactions between virus
      and host. Age and alcohol consumption stand out as important variables in the
      development of cirrhosis.

PMID- 14636482
TI  - Acute atrial fibrillation during dengue hemorrhagic fever.
AB  - Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti.
      Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic
      beats, appear during infection and are attributed to viral myocarditis. However,
      supraventricular arrhythmias have not been reported. We present a case of acute
      atrial fibrillation, with a rapid ventricular rate, successfully treated with
      intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who
      had no structural heart disease.

PMID- 14636483
TI  - Case report: spontaneous rupture of the spleen due to dengue fever.
AB  - Spontaneous rupture of the spleen has been described in cases of hematologic,
      neoplasic and infectious diseases, or resulting from pancreatitis. We report a
      rare case of spontaneous splenic rupture, and favorable evolution after
      splenectomy, in a patient with dengue fever, which occurred during the last
      outbreak of dengue fever in Brazil.

PMID- 14636484
TI  - Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute
      lymphoid leukemia patient.
AB  - Fungal infections caused by Candida species have increased in incidence during
      the past two decades in England, North America and Europe. Candidal arthritis is
      rare in patients who are not intravenous drug users or are who not using a
      prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia,
      who developed Candida tropicalis arthritis during an aplastic period after
      chemotherapy. This is the eighth case described in the literature of C.
      tropicalis causing arthritis without intra-articular inoculation. We call
      attention to an unusual first sign of fungal infection: septic arthritis without
      intra-articular inoculation. However, this case differs from the other seven,
      since despite therapy a fast and lethal evolution was observed. We reviewed
      reported cases, incidence, risk factors, mortality and treatment of neutropenic
      patients with fungal infections.

PMID- 14636485
TI  - Fulminant citrobacter meningitis with multiple periventricular abscesses in a
      three-month-old infant.
AB  - Citrobacter, a Gram-negative enteric bacillus, is a rare cause of septicemia and
      meningitis, seldom reported beyond the neonatal period. It is characterized by a
      fulminant clinical course and a high incidence of complications, including brain
      abscesses. We studied a three-month-old infant with Citrobacter meningitis, who
      developed acute communicating hydrocephalus and multiple periventricular brain
      abscesses while on treatment. The patient died, despite intensive antibiotic
      treatment directed towards the causative organism, C. diversus.

PMID- 14636486
TI  - Treatments for spasticity and pain in multiple sclerosis: a systematic review.
AB  - OBJECTIVES: To identify the drug treatments currently available for the
      management of spasticity and pain in multiple sclerosis (MS), and to evaluate
      their clinical and cost-effectiveness. DATA SOURCES: Electronic bibliographic
      databases, National Research Register, MRC Clinical Trials Register and the US
      National Institutes of Health Clinical Trials Register. REVIEW METHODS:
      Systematic searches identified 15 interventions for the treatment of spasticity
      and 15 interventions for treatment of pain. The quality and outcomes of the
      studies were evaluated. Reviews of the treatment of spasticity and pain when due
      to other aetiologies were also sought. RESULTS: There is limited evidence of the
      effectiveness of four oral drugs for spasticity: baclofen, dantrolene, diazepam
      and tizanidine. Tizanidine appears to be no more effective than comparator drugs
      such as baclofen and has a slightly different side-effects profile. Despite
      claims that it causes less muscle weakness, there was very little evidence that
      tizanidine performed any better in this respect than other drugs, although it is
      more expensive. The findings of this review are consistent with reviews of the
      same treatments for spasticity derived from other aetiologies. There is good
      evidence that both botulinum toxin (BT) and intrathecal baclofen are effective in
      reducing spasticity, and both are associated with functional benefit. However,
      they are invasive, and substantially more expensive. None of the studies included
      in the review of pain were designed specifically to evaluate the alleviation of
      pain in patients with MS and there was no consistency regarding the use of
      validated outcome measures. It was suggested that, although expensive, the use of
      intrathecal baclofen may be associated with significant savings in
      hospitalisation costs in relation to bed-bound patients who are at risk of
      developing pressure sores, thus enhancing its cost-effectiveness. No studies of
      cost-effectiveness were identified in the review of pain. There is evidence,
      albeit limited, of the clinical effectiveness of baclofen, dantrolene, diazepam,
      tizanidine, intrathecal baclofen and BT and of the potential cost-effectiveness
      of intrathecal baclofen in the treatment of spasticity in MS. CONCLUSIONS: Many
      of the interventions identified are not licensed for the alleviation of pain or
      spasticity in MS and the lack of evidence relating to their effectiveness may
      also limit their widespread use. Indeed, forthcoming information relating to the
      use of cannabinoids in MS may result in there being better evidence of the
      effectiveness of new treatments than of any of the currently used drugs. It may
      therefore be of value to carry out double-blind randomised controlled trials of
      interventions used in current practice, where outcomes could include functional
      benefit and impact on quality of life. Further research into the development and
      validation of outcomes measures for pain and spasticity may also be useful, as
      perhaps would cost-utility studies.

PMID- 14636488
TI  - [Ultrasound in pneumology: the current situation].

PMID- 14636487
TI  - Systematic review of isolation policies in the hospital management of methicillin
      resistant Staphylococcus aureus: a review of the literature with epidemiological
      and economic modelling.
AB  - OBJECTIVE: To review the evidence for the effectiveness of different isolation
      policies and screening practices in reducing the incidence of methicillin
      resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital in
      patients. To develop transmission models to study the effectiveness and cost
      effectiveness of isolation policies in controlling MRSA. DATA SOURCES: MEDLINE,
      EMBASE, CINAHL, The Cochrane Library and SIGLE (1966-2000). Hand-searching key
      journals. No language restrictions. REVIEW METHODS: Key data were extracted from
      articles reporting MRSA-related outcomes and describing an isolation policy in a
      hospital with epidemic or endemic MRSA. No quality restrictions were imposed on
      studies using isolation wards (IW) or nurse cohorting (NC). Other studies were
      included if they were prospective or employed planned comparisons of
      retrospective data. Stochastic and deterministic models investigated long-term
      transmission dynamics, studying the effect of a fixed capacity IW, producing
      economic evaluations using local cost data. RESULTS: A total of 46 studies were
      accepted: 18 IWs, 9 NC, 19 other isolation policies. Most were interrupted time
      series, with few planned formal prospective studies. All but one reported
      multiple interventions. Consideration of potential confounders, measures to
      prevent bias, and appropriate statistical analysis were mostly lacking. No
      conclusions could be drawn in a third of studies. Most others provided evidence
      consistent with reduction of MRSA acquisition. Six long interrupted time series
      provided the strongest evidence. Four of these provided evidence that intensive
      control measures which included patient isolation were effective in controlling
      MRSA. In two others IW use failed to prevent endemic MRSA. There was no robust
      economic evaluation. Models showed that improving the detection rate or ensuring
      adequate isolation capacity reduced endemic levels, with substantial savings
      achievable. CONCLUSIONS: Major methodological weaknesses and inadequate reporting
      in published research mean that many plausible alternative explanations for
      reductions in MRSA acquisition associated with interventions cannot be excluded.
      No well-designed studies allow the role of isolation measures alone to be
      assessed. Nonetheless, there is evidence that concerted efforts that include
      isolation can reduce MRSA even when endemic. Little evidence was found to suggest
      that current isolation measures recommended in the UK are ineffective, and these
      should continue to be applied until further research establishes otherwise. The
      studies with the strongest evidence, together with the results of the modelling,
      provide testable hypotheses for future research. Guidelines to facilitate design
      of future research are produced.

PMID- 14636489
TI  - [Validation study of a polygraphic screening device (BREAS SC20) in the diagnosis
      of sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To validate the BREAS SC20 (Breas Medical AB, Molnlyke, Sweden)
      polygraphic screening device, comparing it with conventional polysomnography
      (PSG), in the diagnosis of sleep apnea-hypopnea syndrome. A validity study of the
      diagnostic test was carried out at the sleep clinic of a tertiary hospital.
      PATIENTS AND METHODS: Seventy patients clinically suspected of sleep apnea
      hypopnea syndrome and treated at the sleep laboratory of the Hospital
      Txagorritxu, Vitoria, Spain, from November, 2001 until August, 2002 were
      consecutively enrolled in the study. Patient characteristics, comorbidities, and
      results on the Epworth sleepiness scale were recorded. The apneahypopnea index
      (AHI) per hour of sleep was determined by PSG; the respiratory events index (REI)
      per hour of screening was determined by the polygraphic screening device.
      RESULTS: Sixty studies were valid (77% were men; mean [SD] age: 51.6 [13.2]; body
      mass index: 30.3 [5]; AHI: 31.0 [27.6]). The intraclass correlation coefficient
      between the AHI by PSG and the manual REI was 0.92. The mean difference between
      the AHI and the manual REI was 2.92 (9.75). The area under the receiver operating
      characteristic curve was 0.924 for the cut point AHI >or =5. The optimal cut
      point for an AHI > or = 5 was 3.6 in the REI (98% sensitivity). The respiratory
      screening device correctly classified 90% to 95% of the patients. CONCLUSIONS:
      The BREAS SC20 is a valid system for identifying patients clinically suspected of
      sleep apnea-hypopnea syndrome.

PMID- 14636490
TI  - [Comparison between automatic and manual analysis in the diagnosis of obstructive
      sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To compare automatic and manual analysis of neurological and
      respiratory variables obtained with the SomnoStar alpha 4100, a 16-channel
      polysomnographic system. PATIENTS AND METHOD: Twenty-eight patients suspected of
      obstructive sleep apnea-hypopnea syndrome were enrolled and given conventional
      polysomnographic tests. The order of automatic and manual reading of respiratory
      episodes, sleep stages, and arousals was randomized. We assessed agreement with
      the intraclass correlation coefficient and plotted standardized differences
      against standardized means, using the Bland-Altman method. RESULTS: Poor
      agreement was observed between the 2 types of analysis of sleep stages,
      especially for REM and deep sleep stages. Agreement was good for apneic episodes
      among the respiratory variables; however, automatic analysis underestimated
      hypopneas. If manual analysis is considered the gold standard at the apnea
      hypopnea index cut point greater than 10, automatic analysis obtained a
      sensitivity of 55%, a specificity and positive predictive value of 100%, a
      negative predictive value of 47%, and an overall diagnostic yield of 67.8%.
      CONCLUSIONS: The automatic analysis of the SomnoStar 4100 system provides an
      unsatisfactory reading of sleep stages and respiratory episodes, especially
      hypopneas.

PMID- 14636491
TI  - [Pharmacoeconomic study of antibiotic therapy for exacerbations of chronic
      bronchitis and chronic obstructive pulmonary disease in Latin America].
AB  - Chronic obstructive pulmonary disease (COPD) and chronic bronchitis are highly
      prevalent diseases. Studies designed to analyze the economic impact of these
      diseases in Latin American countries have not previously been published. In the
      present study we analyzed the direct health care costs of treating patients with
      exacerbations of chronic bronchitis and COPD in Argentina, Brazil, Colombia,
      Ecuador, Mexico, Peru, and Venezuela, applying the real cost of drugs and medical
      acts in those 7 countries to the pattern of treatment and outcomes obtained from
      a study carried out in primary care settings in Spain. The mean direct health
      care cost ranged from US $98 in Colombia to $329 in Argentina. Most of the cost
      was related to failure of therapy, which accounted for 52% of the total cost of
      exacerbation, with the lowest rate in Colombia at 28.6% and the highest in
      Ecuador at 59.3% The cost of antibiotic therapy represented 19% of the total
      cost; the rest was owing to other drugs or medical visits. Exacerbations generate
      significant costs for health care systems. There are considerable variations
      related mainly to differences between systems. Antibiotic therapy represents a
      small part of the overall cost. The use of more effective antibiotics, if they
      can reduce failure rates, may be a cost-effective strategy.

PMID- 14636492
TI  - [Prevalence of chronic obstructive pulmonary disease and risk factors in smokers
      and ex-smokers].
AB  - OBJECTIVE: To estimate the prevalence of chronic obstructive pulmonary disease
      (COPD) in smokers and ex-smokers over 40 years of age and describe the associated
      risk factors. MATERIAL AND METHODS: A cross-sectional descriptive study at
      primary care level in which 444 current or ex-smokers 40 years of age or older
      were enrolled. Spirometry was performed with all subjects. If the ratio of forced
      expiratory volume in 1 second to forced vital capacity (FEV1/FVC) was less than
      70%, a bronchodilator test was performed and spirometry was repeated after 2
      inhalations of terbutaline (500 g/dose). If the FEV1/FVC ratio continued to be
      less than 70% and FEV1 less than 80% of predicted, COPD was diagnosed. Age, sex,
      smoking, age smoking began, index of smoking history (packs per day x year) and
      attempts to quit smoking were also recorded. RESULTS: The patients' mean age was
      53.5 years and 65.8% were men. At the time of the study, 248 subjects (55.9%)
      were current smokers. The median age smoking began was 16.5 years and the median
      pack-years index was 26.7. At least 1 attempt to quit had been made by 72.1% of
      the patients. COPD was diagnosed in 70 subjects (24 with the diagnosis previously
      established), representing a prevalence of 16.4% (95% confidence interval, 12.9
      19.9). COPD was serious in 10%. A multifactorial analysis indicated that age and
      smoking history in pack-years were significantly associated with COPD.
      CONCLUSIONS: The prevalence of COPD in our study is slightly higher than in other
      studies, although selection bias may have affected our results given that we were
      unable to contact 11.9% of the population sample. Almost two thirds of cases had
      not been previously diagnosed. Two major risk factors are age and cumulative
      tobacco consumption.

PMID- 14636493
TI  - [Rehabilitation in patients with neuromuscular and chest wall abnormalities].

PMID- 14636494
TI  - [Noninvasive ventilation].

PMID- 14636495
TI  - [Diagnosis and treatment of diffuse interstitial lung diseases].

PMID- 14636496
TI  - [Solitary metastasis to the pancreas in a patient with lung cancer].

PMID- 14636499
TI  - [Community intervention at the cross-roads].

PMID- 14636497
TI  - [Pulmonary infiltrates secondary to carbon monoxide intoxication].

PMID- 14636500
TI  - [Do people attending clinics at our health centre know the amount of alcohol
      consumption that becomes detrimental to health?].
AB  - OBJECTIVES: To evaluate our patients' knowledge of the effects of excess
      drinking; b) to compare this with their awareness of the effects of their day-to
      day drinking habits. DESIGN: Descriptive, randomized, cross-sectional
      questionnaire-based study. Information on alcohol consumption was obtained from
      medical records. SETTING: Primary care center in Chantrea (Navarra province,
      northern Spain). Participants. 351 persons older than 14 years who came to the
      health center. Outcome measures. Number of units of alcohol consumed per day that
      participants considered harmful to health, and number of units consumed per day
      according to information in their medical record. RESULTS: Perception of problems
      associated with excess drinking was good, particularly among women. In general,
      the participants' awareness (including excess drinkers) of the amounts of alcohol
      that could damage their health was good. Although younger persons tended to
      identify as harmful to health limits that were above the recommended figures, we
      found that their consumption was low but was overrecorded. Comparison of the
      intakes that persons identified as harmful with the amounts of alcohol they
      actually consumed showed that the latter was generally related with the former,
      although in 10% of the participants, recorded intake was higher than the limit
      they identified as harmful. This group contained 80% of the drinkers in our
      sample who were considered at risk. CONCLUSIONS: It appears necessary to increase
      the information given to young persons about harmful levels of alcohol intake; b)
      we found no clear evidence of risk drinking among younger persons; this will
      require questioning about their week-end drinking habits; c) risk drinkers know
      the limits of consumption that can damage their health, but their alcohol
      consumption is incongruent with this knowledge.

PMID- 14636501
TI  - [Commentary: Is it possible to define the limits of non-damaging alcohol
      consumption?].

PMID- 14636502
TI  - [A system, developed by prescribing doctors, of indicators of the quality of
      pharmaceutical prescription in primary care].
AB  - OBJECTIVE: To work out a system of indicators and standards, designed by means of
      a consensus group of general practitioners, that enables evaluation of the
      quality of Primary Care prescription to be improved. Design. Informal consensus
      method. SETTING: A PC area in Asturias with 156 614 inhabitants and 9 health
      centres.Participants. Nine PC doctors accepted voluntarily to take part in the
      project. METHOD: A consensus group of nine PC doctors was formed. At a first
      meeting they worked out some potential indicators of quality of prescription.
      After applying these indicators to the prescription data, a second meeting was
      held, at which the results of applying the indicators along with criteria of
      excellence were used to establish the definitive indicators and their numerical
      values of optimum compliance. RESULTS: It was possible to agree by consensus 11
      indicators of quality of prescription and their values of optimum compliance.
      Eight of the indicators referred to choice of a medicine within a pharmaco
      therapeutic group; and three, to groups in which the volume of prescription may
      suggest improper usage. CONCLUSIONS: It is feasible for PC doctors to reach a
      consensus on a group of criteria that is perceived as valid for measuring quality
      of prescription and which includes certain impalpable values for determining
      quality.

PMID- 14636503
TI  - [Relationship between ignorance of own weight and cardiovascular risk in primary
      care].
AB  - OBJECTIVES: To evaluate what health-care users know about their own weight, the
      distribution of body fat and the relationship of their level of knowledge with
      cardiovascular risk factors. DESIGN: Descriptive cross-sectional study.Setting.
      Urban health centre. PARTICIPANTS: 240 patients between 15 and 69, chosen by
      consecutive sampling. MAIN MEASUREMENTS: Survey, analysis (n=100), body
      measurements and sphygmomanometry were done. RESULTS: 80.8% of users knew their
      weight to over-95% accuracy. The biggest errors were found in older patients and
      in women. There was great prevalence of male-style obesity (71.3%), even among
      women. The population with greatest errors in knowing their own weight were at
      greater cardiovascular risk. CONCLUSIONS: In elderly people, age and sex
      condition the Body Mass Index and their ignorance of their own weight. There is a
      relationship between this variable and cardiovascular risk factors. This
      relationship supports the taking of individual-specific health education measures
      on obesity in primary care.

PMID- 14636504
TI  - [Contributions of the seventh report of the Joint National Committee. Six years
      on].

PMID- 14636505
TI  - [Protocol for the multi-centre evaluation of the Experimental Programme Promotion
      of Physical Activity (PEPAF)].
AB  - OBJECTIVE: To evaluate the effectiveness of an innovative programme to promote
      physical activity (PEPAF) introduced into the daily consultations of the family
      doctor. DESIGN: Clinical trial with control, randomised for groups of 100
      patients seen by one of the 70 doctors taking part, allocated to two parallel
      groups and monitored for 24 months.Setting. 13 primary care centres coordinated
      through the Network of Research into Preventive and Health Promotion Activities
      conducted in primary care. PARTICIPANTS: Sample with probability of 7000
      sedentary patients, selected from among those who consulted for any reason their
      family doctor during the third quarter of 2003. Patients with cardiovascular
      disease or other problems meaning that exercise could cause adverse effects will
      be excluded. INTERVENTIONS: The doctors allocated to the PEPAF will design a plan
      of physical activity with those patients prepared to make the change. Those not
      prepared to will be briefly counselled and given material to help them. All will
      be monitored at random. The control group doctors will postpone any systematic
      intervention on exercise until after 2005, excepting those patients whose health
      problem is directly related to a sedentary life-style. MEASUREMENTS: The main
      measurement of results will be the increase in the level of physical activity
      from the base measurement to those at 3, 6, 12 and 24 months, using 7-day
      physical activity recall. Health-related quality of life (SF 36) and physical
      fitness will also be measured. Variables that might be predictive or confusing,
      such as sex, age, comorbidity, social class, etc., will be considered. Analysis.
      The average changes observed in the two groups will be compared, on the basis of
      intention to treat, through analysis of covariance. We will use mixed-effect
      models able to cover the intra-patient, intra-doctor and intra-centre
      correlation.

PMID- 14636506
TI  - [Medical counseling to promote smoking cessation during pregnancy: clinical guide
      lines for health professionals].

PMID- 14636507
TI  - [First Internet survey on the symptom of acidity].

PMID- 14636508
TI  - [Guillain-Barre syndrome in primary care consultations].

PMID- 14636509
TI  - [Weight gain after giving up tobacco].

PMID- 14636510
TI  - [Electrocardiographic disorders in a patient with cardiac trauma].

PMID- 14636512
TI  - [For the study of causal hypotheses, case-control design is superior to cross
      sectional design].

PMID- 14636511
TI  - [Sternoclavicular tubercular arthritis].

PMID- 14636513
TI  - [They don't take any notice of us because they don't know us].

PMID- 14636515
TI  - [Pediatric research and scientific publications].

PMID- 14636516
TI  - [Critical care helicopter transport. Report of 224 cases].
AB  - OBJECTIVE: To report a 5-year experience of pediatric helicopter transport and
      describe its characteristics, the composition of the team, its indications and
      the advantages of air versus ground transport. METHODS: A total of 224 flights
      over a 5-year period were retrospectively analyzed. The team was composed of a
      pediatrician and a pediatric nurse from the Pediatric Department of Hospital Sant
      Pau and was available 365 days per year from sunrise to sunset. The helicopters
      belonged to the Royal Automobile Club of Catalonia and were coordinated by the
      Emergency Medical Service. The area covered was Catalonia and Andorra. The number
      of patients, age, sex, diagnosis, and response and stabilization times were
      recorded. RESULTS: There were 220 patients (139 males and 81 females). Six
      patients died in the primary hospital before transport. Seven flights were
      canceled because of adverse weather, engine breakdown, or family refusal. Three
      twin transportations were performed. A total of 214 patients were transported in
      224 flights. The mean times (in minutes) were: from emergency call to takeoff:
      15; flight time: 39; between landing to the emergency room: 10. The mean
      stabilization time was 42 min. CONCLUSIONS: Helicopter transportation of
      critically-ill children by specialist teams of pediatricians and nurses shortens
      response time in isolated areas with poor transport. The lower number of
      accelerations and vibrations of the helicopter provides greater stability during
      transport, especially in trauma patients. Both transport models, air and ground,
      should be complementary.

PMID- 14636517
TI  - [Short course treatment for visceral leishmaniasis with liposomal amphotericin B
      in immunocompetent patients].
AB  - INTRODUCTION: Visceral leishmaniasis is endemic in southern Europe. Traditional
      treatment consists of pentavalent antimonial compounds. However, treatment
      failures, the treatment's long duration, and toxicity have led to the
      introduction of new therapies, such as liposomal amphotericin B (LAB). In this
      study we evaluate the safety and efficacy of LAB at a maximum dose of 4 mg/kg/day
      on days 1, 2, 3, 4, 5, and 10. PATIENTS AND METHODS: A prospective,
      observational, open study was conducted in 13 Spanish centers. The diagnosis of
      visceral leishmaniasis was based on visualization of Leishmanias sp. in bone
      marrow aspirate or culture or positive serology together with compatible clinical
      symptoms. RESULTS: Thirty-two immunocompetent children aged from 7 months to 7
      years were treated. All the children had rapid clinical response and bone marrow
      aspirate performed on day 21 was normal in the 24 patients (100 %) who underwent
      this procedure. In the remaining eight children efficacy was assessed by clinical
      response. Two relapses were observed. Cure was achieved in 18 patients (90.0 %)
      and in 87.5 % of the patients with microbiological confirmation of the disease.
      No adverse events were detected. CONCLUSIONS: A total dosage of 24 mg/kg of
      liposomal amphotericin B administered in 6 doses within 10 days is safe and
      effective for the treatment of visceral leishmaniasis and reduces the length of
      hospital stay.

PMID- 14636518
TI  - [Tobacco, infant feeding, and wheezing in the first three years of life].
AB  - BACKGROUND: Wheezing lower respiratory tract diseases are frequent and
      troublesome in young children. However, the only avoidable risk factors for them
      are tobacco smoke exposure and feeding practices. OBJECTIVE: To measure the
      influence of these avoidable factors on the risk of wheeze in the first 3 years
      of life. METHODS: We performed a population study including all the children born
      between January 1998 and November 2002 who were attended in the same primary
      health center in Palencia (Spain) from birth. Information on family history,
      pregnancy, delivery, and smoking was obtained soon after birth. Feeding practices
      were recorded on monthly visits. Wheezing episodes in the first 3 years of life
      were identified by a pediatrician. RESULTS: Two hundred thirty-four children were
      included and 43 had at least one episode of wheezing. The results were adjusted
      by sex, prematurity, a family history of allergy, having older siblings, maternal
      age, and month of birth. No association was found between wheezing and exclusive
      breast feeding for 3 months (hazard ratio [HR] 5 0.83, 95 % CI: 0.42-1.64), or
      with postnatal exposure to tobacco smoke (HR 5 1.2, 95 % CI: 0.45-2.34). Tobacco
      smoke exposure during pregnancy was associated with a higher risk of wheezing: HR
      5 2.54 (95 % CI: 1.18-5.48). CONCLUSIONS: Prenatal exposure to tobacco smoke is
      the main modifiable risk factor for wheezing diseases in the first 3 years of
      life.

PMID- 14636520
TI  - [Current concepts in stem cell research].
AB  - In the last few years, advances in stem cell research have opened up new horizons
      in the treatment of human diseases and in regenerative medicine. It is not
      unusual to find news on stem cell research in newspapers and other media. This
      review describes some basic concepts in research needed to understand the medical
      literature on stem cells and to provide the information and bibliography
      necessary to be up to date in one of the subjects that has generated the greatest
      number of publications in the last few years.

PMID- 14636519
TI  - [Utility of octyl 2-cyanoacrylate in pediatric surgery].
AB  - OBJECTIVE: The aim this study was to demonstrate the utility and suitability of
      octyl-2-cianocrylate in cutaneus repair of different conditions in the pediatric
      population. Octyl-2-cianocrylate is a topical tissular adhesive which can be used
      on skin and which has been tested in surgical practice as a wound sealant,
      avoiding the use of conventional sutures. MATERIAL AND METHODS: We applied octyl
      2-cianocrylate in 100 patients with skin wounds smaller than 5 cm. The patients
      were distributed as follows: Emergency department: simple sharp wounds in the
      face and extremities (20 patients); surgical block: surgical wounds in 80
      patients with the following conditions: inguinal hernia (20 patients),
      cryptorchidism (20 patients), umbilical hernia (10 patients), hypospadias (17
      patients), post-hypospadias fistula repair (8 patients) and cleft lip (5
      patients). The results were analyzed in terms of efficacy, cosmetic result,
      procedure time, material used, and patient comfort. CONCLUSIONS: Octyl-2
      cianocrylate was easier to use than conventional sutures in all its applications,
      requiring less time than conventional sutures and therefore lowering the cost per
      procedure.

PMID- 14636521
TI  - [Determinants of uremia elevation in the first days of life in premature infants
      born before 30 weeks of gestation].
AB  - OBJECTIVE: To identify the determinants associated with uremia elevation in the
      first days of life in extremely premature infants. METHODS: We performed a
      prospective cohort study in a cohort of neonates born at less than 30 weeks of
      gestation. RESULTS: Forty-eight preterm infants were included, of which 10 died.
      The mean fluid administration was 55, 72, 88 and 124 mL/kg on the first, second,
      third and seventh days of life. Amino acid doses were low in the first two days
      of life and were unrelated to uremia elevation. Thirty-one percent of the infants
      presented hypernatremia. Uremia was measured in 31 infants between the fifth and
      tenth days of life and 12 infants (38.7 %) had uremia values of 100 mg/dL or
      higher, without creatinine elevation. All of these infants were born at less than
      27 weeks of gestation, weighed less than 850 grams at birth, and showed greater
      weight loss (19.2 % vs. 13.8 %; p 5 0.037) and higher natremia (150.2 mEq/L vs.
      146.6 mEq/L; p 5 0.023). The use of furosemide increased the risk of elevated
      uremia (relative risk: 2.54; 95 % confidence interval: 1.05 6.14). CONCLUSIONS:
      Total uremia of 100 mg/dL or higher was associated with dehydration, greater
      weight loss, higher natremia, furosemide use, lower gestational age, and lower
      birth weight.

PMID- 14636522
TI  - [Cost benefit analysis of body surface cultures at a neonatal unit].
AB  - INTRODUCTION: Infection continues to be a cause of concern in neonatal units. The
      high cost of the body surface cultures used to study infection and their limited
      utility is controversial. MATERIAL AND METHODS: The medical records of newborns
      admitted for suspected infection in 1999 were retrospectively reviewed. Request
      criteria, cost, and the clinical utility of body surface cultures were analyzed.
      RESULTS: In 1999, body surface cultures were requested in 204 newborns admitted
      to hospital (70 % of all admitted newborns). Of these, six were diagnosed with
      bacteremia (6.23/1000; 95 % CI: 5.9-6.5). The most frequently isolated
      microorganisms were Escherichia coli and Streptococcus agalactiae. The total cost
      of body surface cultures was 6,510.95 euros (1,083,331 pesetas). In 25 % of cases
      the results of cultures influenced clinical decision making. The cost necessary
      to obtain clinical repercussion in a patient was 191.50 euros (31,863 pesetas).
      Requesting two body surface cultures only (otic and umbilical) halved the cost
      without diminishing their clinical utility. CONCLUSIONS: A considerable
      percentage of newborns admitted to hospital present suspected infection requiring
      microbiological studies. Although the cost of body surface cultures is high, the
      results of these cultures influence diagnostic and therapeutic decisions in a
      quarter of patients. We do not believe that eliminating the use of these cultures
      would be beneficial. However, their cost can be reduced by carefully selecting
      request criteria and by limiting cultures to two samples (otic and umbilical).

PMID- 14636523
TI  - [Study protocol in metabolic liver disease].

PMID- 14636524
TI  - [Interpretation of the tuberculin test in children].
AB  - Tuberculosis is a resurgent disease in Spain. One of the most important reasons
      is immigration from countries in which this disease is highly endemic. The
      pediatric population is especially susceptible to adults with tuberculosis and an
      infected child represents a sentry event of recent transmission in the community.
      The tuberculin test is an essential instrument in the evaluation of this disease
      and therefore a determining factor in the therapeutic approach adopted. This
      document aims to clarify and unify criteria related to the techniques and
      interpretation of the tuberculin test in children in our environment.

PMID- 14636525
TI  - [Utility of capsule endoscopy in pediatric gastroenterology].
AB  - Wireless endoscopy is a new noninvasive diagnostic method that is able to
      visualize small bowel lesions. The instrument is small and carries a battery and
      microcamera that takes two photographs per second. It is indicated in cases of
      bleeding of unknown origin and for the diagnosis of inflammatory bowel disease,
      among other disorders. To date, it has mainly been used in adults. We believe
      that this instrument could play an important role in the pediatric age group
      since it is noninvasive and can be used to diagnose small bowel lesions, thus
      avoiding unnecessary diagnostic tests. We report the case of a girl with
      suspicion of Crohn's disease that was unconfirmed by conventional endoscopic
      techniques. The capsule showed small bowel lesions compatible with Crohn's
      disease. Corticosteroid treatment was initiated and the patient is now in
      clinical remission.

PMID- 14636526
TI  - [Idiopathic intracranial hypertension: clinical features and outcome].
AB  - Idiopathic intracranial hypertension in children is rare. We analyzed clinical
      presentation and outcome in eight patients (six girls and two boys) diagnosed
      with idiopathic intracranial hypertension. The mean age was 11.1 years. The most
      common clinical features were headache, papilledema and visual disturbance
      (visual loss and diplopia). Response to treatment was satisfactory in all
      patients except one who presented almost complete bilateral amaurosis requiring
      extracranial shunting and who later developed optic atrophy. Outcome is usually
      is benign, but given the possibility of severe loss of visual function, close
      ophthalmic follow-up is recommended until complete resolution.

PMID- 14636527
TI  - [Idiopathic palatopharyngeal hemiparalysis].
AB  - Idiopathic velopalatine palsy is a condition of unknown etiology and is rarely
      seen in childhood. Consequently, diagnosis requires a high degree of suspicion.
      We report a case of sudden onset dysfunction of the lower cranial pairs (IX and
      X) in a 5-year-old girl who was previously asymptomatic. The clinical course was
      favorable and the results of complementary investigations were normal and the
      patient was diagnosed with velopalatine palsy. Based on this case, we aim to
      report our experience of this condition and provide a review of the literature.
      This disease should be suspected in patients aged between 5 and 15 years old who
      present a palsy of the IX and X cranial nerves of sudden onset and without any
      other symptoms in order to rationalize diagnostic and therapeutic tools.
      Treatment is based on support measures. The prognosis is excellent, with a high
      percentage of complete recovery and absence of recurrences.

PMID- 14636528
TI  - [Episodes of convulsive crisis and hemiplegia].

PMID- 14636529
TI  - [Neonatal spinal cord injury and neuroimaging].

PMID- 14636530
TI  - [Value of abdominal ultrasonography in the diagnosis of acute appendicitis].

PMID- 14636531
TI  - [Yield of abdominal ultrasonography in the diagnosis of acute appendicitis.
      Importance of the likelihood ratio].

PMID- 14636532
TI  - [1st National Congress of Pediatric Cardiology (III). Sevilla, Spain. 23-24 May
      2003. Abstracts].

PMID- 14636533
TI  - [Pulmonary embolism: analysis of cases without initial suspicion and sensitivity
      of three clinical models].
AB  - BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is a frequent and severe
      condition. Although clinical models do exist, many patients are wrongly
      diagnosed. Our objective was to evaluate the clinical characteristics of patients
      with PE who are admitted at a hospital without initial clinical suspicion of it.
      We also evaluated the sensitivity of three clinical models in order to categorize
      the pre-test probability of PE. PATIENTS AND METHOD: Retrospective review of
      clinical cases of PE diagnosed in a teaching hospital during one year. We
      compared the clinical features of patients whose PE was not initially suspected
      with those of patients in whom PE was a first diagnosis. The three clinical
      models were applied in all cases. RESULTS: 58 patients were identified. In 15 out
      of them (26%), PE was not an initial diagnosis. Patients without an initial PE
      suspicion were older, and previous surgery was less frequent among them. The
      clinical models exhibited sensitivities (60, 85, 89%) which were lower than those
      previously reported but higher than the doctor's initial clinical suspicion
      (74%). The models showed bad agreement between them (kappa = 0.06-0.1).
      CONCLUSIONS: An initial misdiagnosis of PE is not justified by atypical clinical
      characteristics. The use of clinical models would improve the clinical suspicion.

PMID- 14636534
TI  - [Myocardial infarction. Population case-fatality in seven Spanish autonomous
      communities: the IBERICA Study].
AB  - BACKGROUND AND OBJECTIVE: The magnitude of the problem of myocardial infarction
      (MI) is better understood by assessing the population case-fatality than by
      analyzing only the number of patients attending hospitals. PATIENTS AND METHOD:
      Our data come from the IBERICA Study (Investigation, Specific Search and Registry
      of Acute Myocardial Ischemic Syndrome). Twenty eight-day MI population case
      fatality is described in the population aged 25 to 74 years during 1997 and 1998
      in the following Spanish autonomous communities: Castilla-La Mancha (Toledo and
      Albacete), Catalonia (Girona), Valencia Community (Valencia), Balearic Islands
      (Majorca), Murcia, Navarra and Basque Country. The relationship between case
      fatality and other variables such as sex, age and geographic area is also
      analyzed. RESULTS: A total of 10,660 MI cases were registered, 4,106 of whom died
      within the period of 28 days following the onset of symptoms (38.5%; CI 95%, 37.6
      39.4%). The overall case-fatality was 37.0% (CI 95%, 35.9-38.0%) in men and 44.3%
      (CI 95%, 42.3-46.4%) in women. Death occurred out of hospitals in 2,869 (69.9%)
      cases. An increased case-fatality in women was associated with a higher in
      hospital case-fatality (45% higher than men). The proportion of patients who died
      before reaching a hospital was similar in both genders. Classical symptoms of MI
      were more common among men than women (82.7% vs. 77.6%, p < 0,001). The interval
      between symptoms' onset and hospitalization was 30 minute longer among
      hospitalized women as compared with men (p < 0,001). CONCLUSIONS: Population MI
      case-fatality is high in the seven Spanish autonomous communities studied.
      Approximately 2 out of 3 deaths occur without patients being able to reach a
      hospital. These results emphasize the importance of primary and secondary
      prevention measures and the necessity to design ready-access systems to
      defibrillation and resuscitation manoeuvres for patients with cardiopulmonary
      arrest.

PMID- 14636536
TI  - [Murine typhus in Tenerife. Clinicoepidemiological study and differential
      clinical features with Q fever].
AB  - BACKGROUND AND OBJECTIVE: Our aim was to conduct a study to define the clinical
      and epidemiological characteristics of patients with murine typhus in Tenerife
      island (Canary islands, Spain). Moreover, we investigated the differential
      clinical features of this disease with regard to Q fever. PATIENTS AND METHOD: 5
      year prospective study of patients with murine typhus (1998-2002) admited in a
      reference hospital in Tenerife, Spain. RESULTS: Thirty two patients were
      included. Flea bite and rat exposure were iuncommon (6.25%). The monthly
      distribution showed a peak of incidence in January, August and September, without
      a clear seasonal prevalence. Fever and headache were the most common clinical
      features. Rash was present in 28% of the cases. Both an increase in liver enzyme
      levels (88%) and thrombocytopenia (37.5%) were the most relevant laboratory
      findings. Organ complications were uncommon (18.75%). Antibiotics were
      administered to 90% of patients and cure was achieved in all them. Compared with
      Q fever, patients with murine typhus more commonly had rash (p = 0.006) and
      thrombocytopenia (p < 0.001). CONCLUSION: Murine typhus is an emerging
      rickettsiosis in Tenerife and must be considered in the differential diagnosis
      with Q fever.

PMID- 14636537
TI  - [Complex diseases: rheumatoid arthritis as a model of study].

PMID- 14636538
TI  - [Autoantibodies in the diagnosis of rheumatoid arthritis. Utility of anti-cyclic
      citrullinated peptides].
AB  - Rheumatoid arthritis (RA) is one of the commonest inflammatory joint diseases,
      affecting about 1% of population. Despite its high prevalence, many aspects of
      its etiopathogeny remain unclarified. Recently, some important findings related
      to RA pathogenesis with a number of consequences on the treatment and prognosis
      of this aggressive disease have been reported. It is important to diagnose and to
      treat the disease early to avoid long-term damage. However, the search for a
      specific and sensitive serological test to early identify RA patients has yielded
      poor results. Autoantibodies are found in the sera of RA patients with a variable
      prevalence and have been classified into RA-specific and RA-unspecific
      antibodies. It has been recently demonstrated that many of those RA-specific
      autoantibodies recognize peptides that contain citrulline residues and, thus, a
      new test to measure the presence of anti-cyclic citrullinated peptides (CCP)
      antibodies has been developed. Research publications about the utility of anti
      CCP antibodies not only in the diagnosis, but also in the prognosis, of RA are
      increasing exponentially. In fact, the value of the measurement of anti-CCP
      antibodies is already widely recognized. This review summarizes the most
      important data about the autoantibodies employed to date in the diagnosis of RA,
      including anti-CCP antibodies.

PMID- 14636539
TI  - [Osteoporosis 2003].

PMID- 14636540
TI  - [Interaction of angiotensin-converting enzyme inhibitors with aspirin].

PMID- 14636541
TI  - [Unsatisfaction factors of resident physicians].

PMID- 14636542
TI  - [Incidence of new HIV infections: the importance of heterosexual transmission
      group].

PMID- 14636543
TI  - [Prognostic accuracy of survival in patients with advanced cancer].

PMID- 14636544
TI  - [A doubtful case of anterior uveitis drug related].

PMID- 14636546
TI  - [Traffic accidents. Assistance to the injured].

PMID- 14636548
TI  - [How can corticosteroid-induced osteoporosis be prevented and treated?].

PMID- 14636547
TI  - [RS3PE syndrome and renal cancer].

PMID- 14636549
TI  - Transcription factors prominently in Lasker Award to Roeder.

PMID- 14636550
TI  - Embryonic stem cell self-renewal, analyzed.
AB  - Maintaining the pluripotency of mouse ES cells requires both LIF (leukemia
      inhibitory factor) and unknown factors in serum. The paper from Ying et al. in
      this issue of Cell shows that BMP (bone morphogenetic protein) can replace serum
      in this capacity, defining molecular requirements for ES cell self-renewal.

PMID- 14636551
TI  - Proteolytic processing in development and leukemogenesis.
AB  - There are now numerous examples in the hematopoietic system of genes that are
      critical for normal hematopoietic development, but when mutated, rearranged, or
      overexpressed, contribute to leukemogenesis. Two papers in this issue of Cell
      provide a fascinating twist on this paradigm, and suggest that proteolytic
      processing of certain of these genes plays an important role both in development
      and in leukemogenesis. These findings also suggest the possibility that proteases
      may be therapeutic targets in leukemia.

PMID- 14636552
TI  - MoMLV reverse transcriptase regulates its own expression.
AB  - A precise ratio of Gag:Gag-Pol expression is required for assembly of infectious
      retroviral virions. In this issue of Cell, Orlova et al. show that MoMLV reverse
      transcriptase binds the translation release factor eRF1, and that this
      interaction promotes translation readthrough to make Gag-Pol.

PMID- 14636553
TI  - HtrA2/Omi, a sheep in wolf's clothing.
AB  - Mammalian mitochondrial HtrA2/Omi was originally described as an apoptosis
      inducer, but rather than having extra cells, mice with mutant HtrA2/Omi suffer
      from a neurodegenerative disease due to progressive mitochondrial damage. This
      suggests that instead of promoting cell death by antagonizing inhibitor of
      apoptosis (IAP) proteins, the primary function of HtrA2/Omi is to handle
      misfolded proteins in the mitochondria.

PMID- 14636554
TI  - The receptors for mammalian sweet and umami taste.
AB  - Sweet and umami (the taste of monosodium glutamate) are the main attractive taste
      modalities in humans. T1Rs are candidate mammalian taste receptors that combine
      to assemble two heteromeric G-protein-coupled receptor complexes: T1R1+3, an
      umami sensor, and T1R2+3, a sweet receptor. We now report the behavioral and
      physiological characterization of T1R1, T1R2, and T1R3 knockout mice. We
      demonstrate that sweet and umami taste are strictly dependent on T1R-receptors,
      and show that selective elimination of T1R-subunits differentially abolishes
      detection and perception of these two taste modalities. To examine the basis of
      sweet tastant recognition and coding, we engineered animals expressing either the
      human T1R2-receptor (hT1R2), or a modified opioid-receptor (RASSL) in sweet
      cells. Expression of hT1R2 in mice generates animals with humanized sweet taste
      preferences, while expression of RASSL drives strong attraction to a synthetic
      opiate, demonstrating that sweet cells trigger dedicated behavioral outputs, but
      their tastant selectivity is determined by the nature of the receptors.

PMID- 14636555
TI  - Homothorax switches function of Drosophila photoreceptors from color to polarized
      light sensors.
AB  - Different classes of photoreceptors (PRs) allow animals to perceive various types
      of visual information. In the Drosophila eye, the outer PRs of each ommatidium
      are involved in motion detection while the inner PRs mediate color vision. In
      addition, flies use a specialized class of inner PRs in the "dorsal rim area" of
      the eye (DRA) to detect the e-vector of polarized light, allowing them to exploit
      skylight polarization for orientation. We show that homothorax is both necessary
      and sufficient for inner PRs to adopt the polarization-sensitive DRA fate instead
      of the color-sensitive default state. Homothorax increases rhabdomere size and
      uncouples R7-R8 communication to allow both cells to express the same opsin
      rather than different ones as required for color vision. Homothorax expression is
      induced by the iroquois complex and the wingless (wg) pathway. However, crucial
      wg pathway components are not required, suggesting that additional signals are
      involved.

PMID- 14636556
TI  - BMP induction of Id proteins suppresses differentiation and sustains embryonic
      stem cell self-renewal in collaboration with STAT3.
AB  - The cytokine leukemia inhibitory factor (LIF) drives self-renewal of mouse
      embryonic stem (ES) cells by activating the transcription factor STAT3. In serum
      free cultures, however, LIF is insufficient to block neural differentiation and
      maintain pluripotency. Here, we report that bone morphogenetic proteins (BMPs)
      act in combination with LIF to sustain self-renewal and preserve multilineage
      differentiation, chimera colonization, and germline transmission properties. ES
      cells can be propagated from single cells and derived de novo without serum or
      feeders using LIF plus BMP. The critical contribution of BMP is to induce
      expression of Id genes via the Smad pathway. Forced expression of Id liberates ES
      cells from BMP or serum dependence and allows self-renewal in LIF alone. Upon LIF
      withdrawal, Id-expressing ES cells differentiate but do not give rise to neural
      lineages. We conclude that blockade of lineage-specific transcription factors by
      Id proteins enables the self-renewal response to LIF/STAT3.

PMID- 14636557
TI  - Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene
      expression.
AB  - The Mixed-Lineage Leukemia gene (MLL/HRX/ALL1) encodes a large nuclear protein
      homologous to Drosophila trithorax that is required for the maintenance of HOX
      gene expression. MLL is cleaved at two conserved sites generating N320 and C180
      fragments, which heterodimerize to stabilize the complex and confer its
      subnuclear destination. Here, we purify and clone the protease responsible for
      cleaving MLL. We entitle it Taspase1 as it initiates a class of endopeptidases
      that utilize an N-terminal threonine as the active site nucleophile to proteolyze
      polypeptide substrates following aspartate. Taspase1 proenzyme is
      intramolecularly proteolyzed generating an active 28 kDa alpha/22 kDa beta
      heterodimer. RNAi-mediated knockdown of Taspase1 results in the appearance of
      unprocessed MLL and the loss of proper HOX gene expression. Taspase1 coevolved
      with MLL/trithorax as Arthropoda and Chordata emerged from Metazoa suggesting
      that Taspase1 originated to regulate complex segmental body plans in higher
      organisms.

PMID- 14636558
TI  - Neutrophil elastase cleaves PML-RARalpha and is important for the development of
      acute promyelocytic leukemia in mice.
AB  - The fusion protein PML-RARalpha, generated by the t(15;17)(q22;q11.2)
      translocation associated with acute promyelocytic leukemia (APL), initiates APL
      when expressed in the early myeloid compartment of transgenic mice. PML-RARalpha
      is cleaved in several positions by a neutral serine protease in a human myeloid
      cell line; purification revealed that the protease is neutrophil elastase (NE).
      Immunofluorescence localization studies suggested that the cleavage of PML
      RARalpha must occur within the cell, and perhaps, within the nucleus. The
      functional importance of NE for APL development was assessed in NE deficient
      mice. Greater than 90% of bone marrow PML-RARalpha cleaving activity was lost in
      the absence of NE, and NE (but not Cathepsin G) deficient animals were protected
      from APL development. Primary mouse and human APL cells also contain NE-dependent
      PML-RARalpha cleaving activity. Since NE is maximally produced in promyelocytes,
      this protease may play a role in APL pathogenesis by facilitating the
      leukemogenic potential of PML-RARalpha.

PMID- 14636559
TI  - Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic
      release factor 1 to modulate suppression of translational termination.
AB  - The pol (for polymerase) gene of the murine leukemia viruses (MuLVs) is expressed
      in the form of a large Gag-Pol precursor protein by the suppression of
      translational termination, or enhanced readthrough, of a UAG stop codon at the
      end of gag. A search for cellular proteins that interact with the reverse
      transcriptase of Moloney MuLV resulted in the identification of eRF1, the
      eukaryotic translation release factor 1. The proteins bound strongly in vitro,
      and the overexpression of eRF1 resulted in the RT-dependent incorporation of the
      protein into assembling virion particles. The overexpression of RT in trans
      enhanced the translational readthrough of a reporter construct containing the Gag
      Pol boundary region. Noninteracting mutants of RT failed to synthesize adequate
      levels of Gag-Pol and could not replicate. These results suggest that RT enhances
      suppression of termination and that the interaction of RT with eRF1 is required
      for an appropriate level of translational readthrough.

PMID- 14636560
TI  - Temporal regulation of salmonella virulence effector function by proteasome
      dependent protein degradation.
AB  - Salmonella enterica invasion of host cells requires the reversible activation of
      the Rho-family GTPases Cdc42 and Rac1 by the bacterially encoded GEF SopE and the
      GAP SptP, which exert their function at different times during infection and are
      delivered into host cells by a type III secretion system. We found that SopE and
      SptP are delivered in equivalent amounts early during infection. However, SopE is
      rapidly degraded through a proteosome-mediated pathway, while SptP exhibits much
      slower degradation kinetics. The half-lives of these effector proteins are
      determined by their secretion and translocation domains. Chimeric protein
      analysis indicated that delivery of SptP into host cells by the SopE secretion
      and translocation domain drastically shortened its half-life. Conversely,
      delivery of SopE by the SptP secretion and translocation signals significantly
      increased its half-life, resulting in persistent actin cytoskeleton
      rearrangements. This regulatory mechanism constitutes a remarkable example of a
      pathogen's adaptation to modulate cellular functions.

PMID- 14636561
TI  - ACF7: an essential integrator of microtubule dynamics.
AB  - ACF7 is a member of the spectraplakin family of cytoskeletal crosslinking
      proteins possessing actin and microtubule binding domains. Here, we show that
      ACF7 is an essential integrator of MT-actin dynamics. In endodermal cells, ACF7
      binds along microtubules but concentrates at their distal ends and at cell
      borders when polarized. In ACF7's absence, microtubules still bind EB1 and
      CLIP170, but they no longer grow along polarized actin bundles, nor do they pause
      and tether to actin-rich cortical sites. The consequences are less stable, long
      microtubules with skewed cytoplasmic trajectories and altered dynamic
      instability. In response to wounding, ACF7 null cultures activate polarizing
      signals, but fail to maintain them and coordinate migration. Rescue of these
      defects requires ACF7's actin and microtubule binding domains. Thus,
      spectraplakins are important for controlling microtubule dynamics and reinforcing
      links between microtubules and polarized F-actin, so that cellular polarization
      and coordinated cell movements can be sustained.

PMID- 14636562
TI  - The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis.
AB  - Spindle disassembly at the end of mitosis is a complex and poorly understood
      process. Here, we report that the AAA-ATPase Cdc48/p97 and its adapters Ufd1
      Npl4, which have a well-established role in membrane functions, also regulate
      spindle disassembly by modulating microtubule dynamics and bundling at the end of
      mitosis. In the absence of p97-Ufd1-Npl4 function, microtubules in Xenopus egg
      extracts remain as monopolar spindles attached to condensed chromosomes after
      Cdc2 kinase activity has returned to the interphase level. Consequently,
      interphase microtubule arrays and nuclei are not established. Genetic analyses of
      Cdc48, the yeast homolog of p97, reveal that Cdc48 is also required for
      disassembly of mitotic spindles after execution of the mitotic exit pathway.
      Furthermore, Cdc48/p97-Ufd1-Npl4 directly binds to spindle assembly factors and
      regulates their interaction with microtubules at the end of mitosis. Therefore,
      Cdc48/p97-Ufd1-Npl4 is an essential chaperone that regulates transformation of
      the microtubule structure as cells reenter interphase.

PMID- 14636563
TI  - The cycle of nonsense.

PMID- 14636564
TI  - Regulating intertwining proteins.

PMID- 14636565
TI  - A two-tiered transcription regulation mechanism that protects germ cell identity.

PMID- 14636566
TI  - "Getting it on"--GDI displacement and small GTPase membrane recruitment.

PMID- 14636567
TI  - Enigmatic variations: divergent modes of regulating eukaryotic DNA replication.
AB  - Proteins involved in DNA replication are conserved from yeast to mammals,
      suggesting that the mechanism was established at an early stage of eukaryotic
      evolution. In spite of this common origin, recent findings have revealed
      surprising variations in how replication initiation is controlled, implying that
      a conserved mechanism has not necessarily resulted in regulatory conservation.

PMID- 14636568
TI  - Mechanism of 5'-directed excision in human mismatch repair.
AB  - We have developed a purified system that supports mismatch-dependent 5'-->3'
      excision. In the presence of RPA, ATP, and a mismatch, MutSalpha activates 5'-
      >3' excision by EXOI, and excision terminates after removal of the mispair.
      MutSalpha confers high processivity on EXOI, and termination is due to RPA
      dependent displacement of this processive complex from the helix and a weak
      ability of EXOI to reload at the RPA-bound gap in the product, as well as
      MutSalpha- and MutLalpha-dependent suppression of EXOI activity in the absence of
      a mismatch cofactor. As observed in the purified system, excision directed by a
      5' strand break in HeLa nuclear extract can proceed in the absence of MutLalpha
      or PCNA, although 3' excision in the extract system requires both proteins.

PMID- 14636569
TI  - Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a
      signalosome-like subunit and its role in DNA repair.
AB  - We have isolated a holoenzyme complex termed BRCC containing BRCA1, BRCA2, and
      RAD51. BRCC not only displays increased association with p53 following DNA damage
      but also ubiquitinates p53 in vitro. BRCC36 and BRCC45 are novel components of
      the complex with sequence homology to a subunit of the signalosome and proteasome
      complexes. Reconstitution of a recombinant four-subunit complex containing
      BRCA1/BARD1/BRCC45/BRCC36 revealed an enhanced E3 ligase activity compared to
      that of BRCA1/BARD1 heterodimer. In vivo, depletion of BRCC36 and BRCC45 by the
      small interfering RNAs (siRNAs) resulted in increased sensitivity to ionizing
      radiation and defects in G2/M checkpoint. BRCC36 shows aberrant expression in
      sporadic breast tumors. These findings identify BRCC as a ubiquitin E3 ligase
      complex that enhances cellular survival following DNA damage.

PMID- 14636570
TI  - The orientation of mycobacteriophage Bxb1 integration is solely dependent on the
      central dinucleotide of attP and attB.
AB  - Integration of the mycobacteriophage Bxb1 genome into its host chromosome is
      catalyzed by a serine-integrase, a member of the transposon-resolvase family of
      site-specific recombinases. These enzymes use a concerted mechanism of strand
      exchange involving double-stranded cleavages with two-base extensions, and
      covalent protein-DNA linkages via phosphoserine bonds. In contrast to the
      resolvase/invertase recombination systems--where there are strict requirements
      for a specific synaptic complex within which the catalytic potential of the
      enzyme is activated--synapsis of attP and attB by Bxb1 integrase is completely
      promiscuous, aligning the sites with equal proclivity in parallel and
      antiparallel alignments. Moreover, the catalytic potential of Bxb1 integrase is
      fully active in either alignment. As a consequence, the nonpalindromic central
      dinucleotide (5'-GT) at the center of attP and attB is the sole determinant of
      Bxb1 prophage orientation, and a single base pair substitution in the two sites
      is sufficient to eliminate orientation control.

PMID- 14636571
TI  - The crystal structure of the bifunctional primase-helicase of bacteriophage T7.
AB  - Within minutes after infecting Escherichia coli, bacteriophage T7 synthesizes
      many copies of its genomic DNA. The lynchpin of the T7 replication system is a
      bifunctional primase-helicase that unwinds duplex DNA at the replication fork
      while initiating the synthesis of Okazaki fragments on the lagging strand. We
      have determined a 3.45 A crystal structure of the T7 primase-helicase that shows
      an articulated arrangement of the primase and helicase sites. The crystallized
      primase-helicase is a heptamer with a crown-like shape, reflecting an intimate
      packing of helicase domains into a ring that is topped with loosely arrayed
      primase domains. This heptameric isoform can accommodate double-stranded DNA in
      its central channel, which nicely explains its recently described DNA remodeling
      activity. The double-jointed structure of the primase-helicase permits a free
      range of motion for the primase and helicase domains that suggests how the
      continuous unwinding of DNA at the replication fork can be periodically coupled
      to Okazaki fragment synthesis.

PMID- 14636572
TI  - The flap domain is required for pause RNA hairpin inhibition of catalysis by RNA
      polymerase and can modulate intrinsic termination.
AB  - Bacterial RNA polymerase (RNAP) responds to formation of RNA secondary structures
      (hairpins) in newly synthesized RNA. Depending on the spacing of the hairpin from
      the RNA 3' end and the intervening RNA sequence, the hairpin can prolong pausing
      or cause transcriptional termination. At the his pause site, the pause hairpin
      contacts a flexible domain on RNAP called the flap, which forms a critical part
      of a hairpin-interaction site on the enzyme. We report that pause hairpin-flap
      interaction stabilizes an inhibited configuration of RNAP's active site without
      changing RNAP's translocation register. The distal part of the flap (the flap
      tip) is required for the hairpin to affect the active site, but not for hairpin
      formation. In contrast, the flap tip is not required for intrinsic termination,
      but can modulate it at suboptimal termination signals.

PMID- 14636573
TI  - Coordination of p300-mediated chromatin remodeling and TRAP/mediator function
      through coactivator PGC-1alpha.
AB  - Transcriptional coactivators showing physical and functional interactions with
      PPARgamma include the protein acetyl transferase p300, the TRAP/Mediator complex
      that interacts with the general transcription machinery, and the highly regulated
      PGC-1alpha. We show that PGC-1alpha directly interacts with TRAP/Mediator,
      through the PPARgamma-interacting subunit TRAP220, and stimulates TRAP/Mediator
      dependent function on DNA templates. Further, while ineffective by itself, PGC
      1alpha stimulates p300-dependent histone acetylation and transcription on
      chromatin templates in response to PPARgamma. These functions are mediated by
      largely independent PPARgamma, p300, and TRAP220 interaction domains in PGC
      1alpha, whereas p300 and TRAP220 show ligand-dependent interactions with a common
      region of PPARgamma. Apart from showing PGC-1alpha functions both in chromatin
      remodeling and in preinitiation complex formation or function (transcription),
      these results suggest a key role for PGC-1alpha, through concerted but dynamic
      interactions, in coordinating these steps.

PMID- 14636574
TI  - Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome
      biogenesis and cell proliferation.
AB  - The tumor suppressor ARF induces a p53-dependent and -independent cell cycle
      arrest. Unlike the nucleoplasmic MDM2 and p53, ARF localizes in the nucleolus.
      The role of ARF in the nucleolus, the molecular target, and the mechanism of its
      p53-independent function remains unclear. Here we show that ARF interacts with
      B23, a multifunctional nucleolar protein involved in ribosome biogenesis, and
      promotes its polyubiquitination and degradation. Overexpression of B23 induces a
      cell cycle arrest in normal fibroblasts, whereas in cells lacking p53 it promotes
      S phase entry. Conversely, knocking down B23 inhibits the processing of
      preribosomal RNA and induces cell death. Further, oncogenic Ras induces B23 only
      in ARF null cells, but not in cells that retain wild-type ARF. Together, our
      results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and
      cell proliferation via inhibiting B23, and suggest a nucleolar role of ARF in
      surveillance of oncogenic insults.

PMID- 14636575
TI  - Crystal structures of an archaeal class I CCA-adding enzyme and its nucleotide
      complexes.
AB  - CCA-adding enzymes catalyze the addition of CCA onto the 3' terminus of immature
      tRNAs without using a nucleic acid template and have been divided into two
      classes based on their amino acid sequences. We have determined the crystal
      structures of a class I CCA-adding enzyme from Archeoglobus fulgidus (AfCCA) and
      its complexes with ATP, CTP, or UTP. Although it and the class II bacterial
      Bacillus stearothermophilus CCA enzyme (BstCCA) have similar dimensions and
      domain architectures (head, neck, body, and tail), only the polymerase domain is
      structurally homologous. Moreover, the relative orientation of the head domain
      with respect to the body and tail domains, which appear likely to bind tRNA,
      differs significantly between the two enzyme classes. Unlike the class II BstCCA,
      this enzyme binds nucleotides nonspecifically in the absence of bound tRNA. The
      shape and electrostatic charge distribution of the AfCCA enzyme suggests a model
      for tRNA binding that accounts for the phosphates that are protected from
      chemical modification by tRNA binding to AfCCA. The structures of the AfCCA
      enzyme and the eukaryotic poly(A) polymerase are very similar, implying a close
      evolutionary relationship between them.

PMID- 14636576
TI  - Crystal structure of the 2'-specific and double-stranded RNA-activated interferon
      induced antiviral protein 2'-5'-oligoadenylate synthetase.
AB  - 2'-5'-oligoadenylate synthetases are interferon-induced, double-stranded RNA
      activated antiviral enzymes which are the only proteins known to catalyze 2'
      specific nucleotidyl transfer. This crystal structure of a 2'-5'-oligoadenylate
      synthetase reveals a structural conservation with the 3'-specific poly(A)
      polymerase that, coupled with structure-guided mutagenesis, supports a conserved
      catalytic mechanism for the 2'- and 3'-specific nucleotidyl transferases.
      Comparison with structures of other superfamily members indicates that the donor
      substrates are bound by conserved active site features while the acceptor
      substrates are oriented by nonconserved regions. The 2'-5'-oligoadenylate
      synthetases are activated by viral double-stranded RNA in infected cells and
      initiate a cellular response by synthesizing 2'-5'-oligoadenylates, which in turn
      activate RNase L. This crystal structure suggests that activation involves a
      domain-domain shift and identifies a putative dsRNA activation site that is
      probed by mutagenesis, thus providing structural insight into cellular
      recognition of viral double-stranded RNA.

PMID- 14636577
TI  - Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes
      containing hSMG-5 and hSMG-7.
AB  - Eukaryotic mRNAs containing premature termination codons (PTCs) are degraded by a
      process known as nonsense-mediated mRNA decay (NMD). NMD has been suggested to
      require the recognition of PTC by an mRNA surveillance complex containing
      UPF1/SMG-2. In multicellular organisms, UPF1/SMG-2 is a phosphoprotein, and its
      phosphorylation contributes to NMD. Here we show that phosphorylated hUPF1, the
      human ortholog of UPF1/SMG-2, forms a complex with human orthologs of the C.
      elegans NMD proteins SMG-5 and SMG-7. The complex also associates with protein
      phosphatase 2A (PP2A), resulting in dephosphorylation of hUPF1. Overexpression of
      hSMG-5 mutants that retain interaction with P-hUPF1 but which cannot induce its
      dephosphorylation impair NMD, suggesting that NMD requires P-hUPF1
      dephosphorylation. We also show that P-hUPF1 forms distinct complexes containing
      different isoforms of hUPF3A. We propose that sequential phosphorylation and
      dephosphorylation of hUPF1 by hSMG-1 and PP2A, respectively, contribute to the
      remodeling of the mRNA surveillance complex.

PMID- 14636578
TI  - The Wnt/beta-catenin-->Pitx2 pathway controls the turnover of Pitx2 and other
      unstable mRNAs.
AB  - The Wnt/beta-catenin pathway rapidly induces the transcription of the cell-type
      restricted transcription factor Pitx2 that is required for effective cell
      specific proliferation activating growth-regulating genes. Here we report that
      Pitx2 mRNA displays a rapid turnover rate and that activation of the Wnt/beta
      catenin pathway stabilizes Pitx2 mRNA as well as other unstable mRNAs, including
      c-Jun, Cyclin D1, and Cyclin D2, encoded by critical transcriptional target genes
      of the same pathway. Our data indicate that Pitx2 mRNA stabilization is due to a
      reduced interaction of Pitx2 3'UTR with the destabilizing AU-rich element (ARE)
      binding proteins (BPs) KSRP and TTP as well as to an increased interaction with a
      stabilizing ARE-BP, HuR. Pitx2 itself is a mediator of Wnt/beta-catenin-induced
      mRNA stabilization. Our previous and present data support the hypothesis that a
      single pathway can coordinately regulate sequential transcriptional and
      posttranscriptional events leading to an integrated functional gene regulatory
      network.

PMID- 14636579
TI  - Tumorigenic mutations in VHL disrupt folding in vivo by interfering with
      chaperonin binding.
AB  - The eukaryotic chaperonin TRiC/CCT mediates folding of an essential subset of
      newly synthesized proteins, including the tumor suppressor VHL. Here we show that
      chaperonin binding is specified by two short hydrophobic beta strands in VHL
      that, upon folding, become buried within the native structure. These TRiC binding
      determinants are disrupted by tumor-causing point mutations that interfere with
      chaperonin association and lead to misfolding. Strikingly, while unable to fold
      correctly in vivo, some of these VHL mutants can reach the native state when
      refolded in a chaperonin-independent manner. The specificity of TRiC/CCT for
      extended hydrophobic beta strands may help explain its role in folding
      aggregation-prone polypeptides. Our findings reveal a class of disease-causing
      mutations that inactivate protein function by disrupting chaperone-mediated
      folding in vivo.

PMID- 14636580
TI  - PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a
      mechanism for tissue-specific transcriptional regulation.
AB  - The bHLH factors HAND1 and HAND2 are required for heart, vascular, neuronal,
      limb, and extraembryonic development. Unlike most bHLH proteins, HAND factors
      exhibit promiscuous dimerization properties. We report that
      phosphorylation/dephosphorylation via PKA, PKC, and a specific heterotrimeric
      protein phosphatase 2A (PP2A) modulates HAND function. The PP2A targeting-subunit
      B56delta specifically interacts with HAND1 and -2, but not other bHLH proteins.
      PKA and PKC phosphorylate HAND proteins in vivo, and only B56delta-containing
      PP2A complexes reduce levels of HAND1 phosphorylation. During RCHOI trophoblast
      stem cell differentiation, B56delta expression is downregulated and HAND1
      phosphorylation increases. Mutations in phosphorylated residues result in altered
      HAND1 dimerization and biological function. Taken together, these results suggest
      that site-specific phosphorylation regulates HAND factor functional specificity.

PMID- 14636581
TI  - Active and inactive orientations of the transmembrane and cytosolic domains of
      the erythropoietin receptor dimer.
AB  - Binding of erythropoietin to the erythropoietin receptor (EpoR) extracellular
      domain orients the transmembrane (TM) and cytosolic regions of the receptor dimer
      into an unknown activated conformation. By replacing the EpoR extracellular
      domain with a dimeric coiled coil, we engineered TM EpoR fusion proteins where
      the helical TM domains were constrained into seven possible relative
      orientations. We identify one dimeric TM conformation that imparts full activity
      to the cytosolic domain of the receptor and signals via JAK2, STAT proteins, and
      MAP kinase, one partially active orientation that preferentially activates MAP
      kinase, and one conformation corresponding to the inactive receptor. The active
      and inactive conformations were independently identified by computational
      searches for low-energy TM dimeric structures. We propose a specific EpoR
      activated interface and suggest its use for structural and signaling studies.

PMID- 14636582
TI  - Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence
      in the C-terminal region of Frizzled.
AB  - The cytoplasmic protein Dishevelled (Dvl) and the associated membrane-bound
      receptor Frizzled (Fz) are essential in canonical and noncanonical Wnt signaling
      pathways. However, the molecular mechanisms underlying this signaling are not
      well understood. By using NMR spectroscopy, we determined that an internal
      sequence of Fz binds to the conventional peptide binding site in the PDZ domain
      of Dvl; this type of site typically binds to C-terminal binding motifs. The C
      terminal region of the Dvl inhibitor Dapper (Dpr) and Frodo bound to the same
      site. In Xenopus, Dvl binding peptides of Fz and Dpr/Frodo inhibited canonical
      Wnt signaling and blocked Wnt-induced secondary axis formation in a dose
      dependent manner, but did not block noncanonical Wnt signaling mediated by the
      DEP domain. Together, our results identify a missing molecular connection within
      the Wnt pathway. Differences in the binding affinity of the Dvl PDZ domain and
      its binding partners may be important in regulating signal transduction by Dvl.

PMID- 14636583
TI  - Hedgehog signal transduction via Smoothened association with a cytoplasmic
      complex scaffolded by the atypical kinesin, Costal-2.
AB  - The seven-transmembrane protein Smoothened (Smo) transduces extracellular
      activation of the Hedgehog (Hh) pathway by an unknown mechanism to increase
      transcriptional activity of the latent cytoplasmic transcription factor Ci
      (Cubitus interruptus). Here, we present evidence that Smo associates directly
      with a Ci-containing complex that is scaffolded and stabilized by the atypical
      kinesin, Costal-2 (Cos2). This complex constitutively suppresses pathway
      activity, but Hh signaling reverses its regulatory effect to promote Ci-mediated
      transcription. In response to Hh activation of Smo, Cos2 mediates accumulation
      and phosphorylation of Smo at the membrane as well as phosphorylation of the
      cytoplasmic components Fu and Su(fu). Positive response of Cos2 to Hh stimulation
      requires a portion of the Smo cytoplasmic tail and the Cos2 cargo domain, which
      interacts directly with Smo.

PMID- 14636584
TI  - Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth
      factor-stimulated epithelial morphogenesis.
AB  - Activation of the hepatocyte growth factor (HGF) receptor c-met results in the
      regulation of cell-matrix interactions, including the MAPK-dependent stimulation
      of epithelial cell morphogenesis. In the present study we demonstrate that HGF
      stimulates the localization of ERK to sites of cell-matrix interactions and that
      this is mediated by the tyrosine phosphorylation-dependent association of
      inactive ERK and the focal adhesion complex protein paxillin. In addition,
      paxillin was found to associate with the upstream MAP kinases Raf and MEK,
      resulting in a complex that can mediate localized ERK activation. Mutation of the
      ERK binding site in paxillin prevented HGF-stimulated ERK-paxillin association
      and eliminated HGF-induced cell spreading and branching process formation. These
      experiments reveal that paxillin-dependent ERK activation at sites of cell-matrix
      interaction is critical for HGF-stimulated epithelial morphogenesis.

PMID- 14636585
TI  - Mechanisms of proinflammatory cytokine-induced biphasic NF-kappaB activation.
AB  - The transcription factor NF-kappaB regulates genes involved in innate and
      adaptive immune response, inflammation, apoptosis, and oncogenesis.
      Proinflammatory cytokines induce the activation of NF-kappaB in both transient
      and persistent phases. We investigated the mechanism for this biphasic NF-kappaB
      activation. Our results show that MEKK3 is essential in the regulation of rapid
      activation of NF-kappaB, whereas MEKK2 is important in controlling the delayed
      activation of NF-kappaB in response to stimulation with the cytokines TNF-alpha
      and IL-1alpha. MEKK3 is involved in the formation of the IkappaBalpha:NF
      kappaB/IKK complex, whereas MEKK2 participates in assembling the IkappaBbeta:NF
      kappaB/IKK complex; these two distinct complexes regulate the proinflammatory
      cytokine-induced biphasic NF-kappaB activation. Thus, our study reveals a novel
      mechanism in which different MAP3K and IkappaB isoforms are involved in specific
      complex formation with IKK and NF-kappaB for regulating the biphasic NF-kappaB
      activation. These findings provide further insight into the regulation of
      cytokine-induced specific and temporal gene expression.

PMID- 14636586
TI  - Differential phosphorylation and subcellular localization of La RNPs associated
      with precursor tRNAs and translation-related mRNAs.
AB  - The La protein facilitates the production of tRNAs in the nucleus and the
      translation of specific mRNAs in the cytoplasm. We report that human La that is
      phosphorylated on serine 366 (pLa) is nucleoplasmic and associated with precursor
      tRNAs and other nascent RNA polymerase III transcripts while nonphosphorylated
      (np)La is cytoplasmic and associated with a subset of mRNAs that contain 5'
      terminal oligopyrimidine (5'TOP) motifs known to control protein synthesis. Thus,
      La ribonucleoproteins (RNP) exist in distinct states that differ in subcellular
      localization, serine 366 phosphorylation, and associated RNAs. These results are
      consistent with a model in which the relative concentrations of the La S366
      isoforms in different subcellular compartments in conjunction with the relative
      concentrations of specific RNA ligands in these compartments determine the
      differential association of npLa and pLa with their respective classes of
      associated RNAs.

PMID- 14636587
TI  - Functional redundancy of Spb1p and a snR52-dependent mechanism for the 2'-O
      ribose methylation of a conserved rRNA position in yeast.
AB  - In yeast, guide snoRNAs have been assigned to 51 of the 55 rRNA ribose
      methylation sites. LSU-Um2918 is one of the four remaining positions. This
      residue is highly conserved and located in the peptidyl transferase center of the
      ribosome. The equivalent position on the E. coli 23S rRNA is methylated by
      FtsJ/RrmJ which has three yeast homologs: Spb1, involved in biogenesis of LSU;
      Trm7, a tRNA methyltransferase; and Mrm2, a mitochondrial 21S rRNA
      methyltransferase. We demonstrate that a point mutation in the Ado-Met binding
      site of Spb1p affects cell growth but does not abolish methylation of U2918. When
      this mutation is combined with disruption of snR52 (a snoRNA C/D), cell growth is
      severely impaired and U2918 is no longer methylated. In vitro, Spb1p is able to
      methylate U2918 on 60S subunits. Our results reveal the importance of this
      methylation for which two mechanisms coexist: a site-specific methyltransferase
      (Spb1p) and a snoRNA-dependent mechanism.

PMID- 14636588
TI  - A conserved signal-responsive sequence mediates activation-induced alternative
      splicing of CD45.
AB  - Alternative splicing of nascent transcripts is a widespread mechanism for
      altering protein expression in response to extracellular stimuli. However, little
      is known about the sequences that mediate signal-induced alternative splicing,
      complicating efforts to identify genes whose splicing may be regulated in
      response to a particular stimuli. Here we define a sequence element that is both
      the primary determinant of CD45 variable exon exclusion following T cell
      stimulation by PMA and is sufficient to confer activation-induced skipping of a
      heterologous exon. Additionally, we show that this regulatory element has
      homology to sequences in other signal-regulated genes, suggesting that the
      alternative splicing of large families of genes may be regulated by common
      signaling pathways.

PMID- 14636589
TI  - Methylation of histone H3 K4 mediates association of the Isw1p ATPase with
      chromatin.
AB  - Set1p methylates lysine 4 (K4) of histone H3 and regulates the expression of many
      genes in yeast. Here we use a biochemical approach to identify a protein, Isw1p,
      which recognizes chromatin preferentially when it is di- and trimethylated at K4
      H3. We show that on certain actively transcribed genes, the Isw1p chromatin
      remodeling ATPase requires K4 H3 methylation to associate with chromatin in vivo.
      Analysis of one such gene, MET16, shows that the enzymatic activities of Set1p
      and Isw1p are functionally connected: Set1p methylation and Isw1p ATPase generate
      specific chromatin changes at the 5' end of the gene, are necessary for the
      correct distribution of RNA polymerase II over the coding region, and are
      required for the recruitment of the cleavage and polyadenylation factor Rna15p.
      These results indicate that K4 H3 methylation and Isw1p ATPase activity are
      intimately linked in regulating transcription of certain genes in yeast.

PMID- 14636590
TI  - Chromatin remodeling in vivo: evidence for a nucleosome sliding mechanism.
AB  - Members of the ISWI family of chromatin remodeling factors exhibit ATP-dependent
      nucleosome sliding, loading, and spacing activities in vitro. However, it is
      unclear which of these activities are utilized by ISWI complexes to remodel
      chromatin in vivo. We therefore sought to identify the mechanisms of chromatin
      remodeling by Saccharomyces cerevisiae Isw2 complex at its known sites of action
      in vivo. To address this question, we developed a method of identifying
      intermediates of the Isw2-dependent chromatin remodeling reaction as it
      proceeded. We show that Isw2 complex catalyzes nucleosome sliding at two
      different classes of target genes in vivo, in each case sliding nucleosomes
      closer to the promoter regions. In contrast to its biochemical activities in
      vitro, nucleosome sliding by Isw2 complex in vivo is unidirectional and localized
      to a few nucleosomes at each site, suggesting that Isw2 activity is constrained
      by cellular factors.

PMID- 14636591
TI  - Mechanism of repression by Bacillus subtilis CcpC, a LysR family regulator.
AB  - Bacillus subtilis CcpC is a LysR family transcriptional regulatory protein that
      negatively regulates genes encoding enzymes of the tricarboxylic acid branch of
      the Krebs cycle. In the present work, the promoter region of the aconitase (citB)
      gene was used to investigate the mechanism of repression by CcpC. The binding of
      CcpC to the citB promoter region was shown to depend on DNA elements located near
      positions -66 and -27. Binding to these elements induced a bend in the DNA at
      position -41. Introduction of mutations in the -27 region and the presence of
      citrate, the inducer, had similar effects. In either case, citB expression was
      derepressed in vivo, the affinity of CcpC binding was reduced in vitro, the angle
      of the bend was relaxed, and RNA polymerase gained greater access to the -35
      region of the promoter.

PMID- 14636592
TI  - The crystal structure of murine CMP-5-N-acetylneuraminic acid synthetase.
AB  - Sialic acids are activated by CMP-5-N-acetylneuraminic acid synthetase prior to
      their transfer onto oligo- or polysaccharides. Here, we present the crystal
      structure of the N-terminal catalytically active domain of the murine 5-N
      acetylneuraminic acid synthetase in complex with the reaction product. In
      contrast to the previously solved structure of 5-N-acetylneuraminic acid
      synthetase from Neisseria meningitidis and the related CMP-KDO-synthetase of
      Escherichia coli, the murine enzyme is a tetramer, which was observed with the
      active sites closed. In this conformation a loop is shifted by 6A towards the
      active site and thus an essential arginine residue can participate in catalysis.
      Furthermore, a network of intermolecular salt-bridges and hydrogen bonds in the
      dimer as well as hydrophobic interfaces between two dimers indicate a cooperative
      behaviour of the enzyme. In addition, a complex regulation of the enzyme activity
      is proposed that includes phosphorylation and dephosphorylation.

PMID- 14636593
TI  - An alternative route for the folding of large RNAs: apparent two-state folding by
      a group II intron ribozyme.
AB  - Despite a growing literature on the folding of RNA, our understanding of tertiary
      folding in large RNAs derives from studies on a small set of molecular examples,
      with primary focus on group I introns and RNase P RNA. To broaden the scope of
      RNA folding models and to better understand group II intron function, we have
      examined the tertiary folding of a ribozyme (D135) that is derived from the self
      splicing ai5gamma intron from yeast mitochondria. The D135 ribozyme folds
      homogeneously and cooperatively into a compact, well-defined tertiary structure
      that includes all regions critical for active-site organization and substrate
      recognition. When D135 was treated with increasing concentrations of Mg(2+) and
      then subjected to hydroxyl radical footprinting, similar Mg(2+) dependencies were
      seen for internalization of all regions of the molecule, suggesting a highly
      cooperative folding behavior. In this work, we show that global folding and
      compaction of the molecule have the same magnesium dependence as the local
      folding previously observed. Furthermore, urea denaturation studies indicate
      highly cooperative unfolding of the ribozyme that is governed by thermodynamic
      parameters similar to those for forward folding. In fact, D135 folds
      homogeneously and cooperatively from the unfolded state to its native, active
      structure, thereby demonstrating functional reversibility in RNA folding. Taken
      together, the data are consistent with two-state folding of the D135 ribozyme,
      which is surprising given the size and multi-domain structure of the RNA. The
      findings establish that the accumulation of stable intermediates prior to
      formation of the native state is not a universal feature of RNA folding and that
      there is an alternative paradigm in which the folding landscape is relatively
      smooth, lacking rugged features that obstruct folding to the native state.

PMID- 14636594
TI  - An unusual sugar conformation in the structure of an RNA/DNA decamer of the
      polypurine tract may affect recognition by RNase H.
AB  - Retroviral conversion of single-stranded RNA into double-stranded DNA requires
      priming for each strand. While host cellular t-RNA serves as primer for the first
      strand, the viral polypurine tract (PPT) is primer for the second. Therefore,
      polypurine tracts of retroviruses are essential for viral replication by reverse
      transcriptase (RT). These purine tracts are resistant to cleavage during first
      strand synthesis. In obtaining the primer for second strand synthesis, the RNase
      H function of RT must cleave the PPT exactly for in vivo transcription to proceed
      efficiently and proper integration to occur. At the RNase H active site the
      protein makes contacts primarily along the backbone, with hydrogen bonds to the
      sugar-phosphate oxygen atoms. A high-resolution structure (1.10A) of the first
      ten base-pairs of the RNA/DNA hybrid PPT, r-(c-a-a-a-g-a-a-a-a-g)/d-(C-T-T-T-T-C
      T-T-T-G), contains the highly deformable r-(a-g-a) steps found in retroviral
      polypurine tracts. This r-(a-g-a) motif is utilized in the "unzipping" or
      unpairing of bases that occurs when RT binds a malleable PPT. Another unusual
      feature found in our high-resolution PPT structure is the sugar switch at RNA
      adenine 2. All the RNA sugars are the expected C3'-endo, except sugar 2, which is
      C2'-endo, characteristic of B-form sugars. This local A-to-B conversion adversely
      affects the pattern of hydrogen bonds from protein to sugar-phosphate backbone,
      disrupting the catalytic site. Disruption could cause the enzyme to pause at the
      5'-end of the PPT, leaving it intact. Pyrimidine-purine (YR) steps are most
      deformable and the T-A step especially can undergo A-to-B transitions readily.

PMID- 14636595
TI  - Overlap of nuclear localisation signal and specific DNA-binding residues within
      the zinc finger domain of PacC.
AB  - The transcription factor PacC, mediating regulation of gene expression by ambient
      pH in the genetically amenable fungus Aspergillus nidulans, contains a three zinc
      finger DNA-binding domain (zf-DBD) including a nuclear localisation signal (NLS).
      We selected 38 novel mutations impairing PacC function, of which 21 missense
      mutations identify individual residues essential for zf-DBD structure/function.
      Our functional analysis agrees with our previous conclusion that finger 1 does
      not bind DNA and provides in vivo evidence that Trp80 and Trp116, located in the
      Cys knuckles of adjacent zinc fingers, are critical for zf-DBD
      structure/function. In the finger 3 alpha-helix, Gln155 (+4) is specifically
      involved in contacting DNA, while the major role of Lys159 (+6) resides in the
      nuclear localisation of the protein. In contrast, Lys158 is essential for DNA
      binding and for nuclear localisation. As finger 3 suffices to drive nuclear
      localisation of green fluorescent protein, we conclude that it contains an NLS
      including essential Lys158 and Lys159. These residues are within an alpha-helical
      basic sequence that is completely conserved amongst zinc fingers of the
      PacC/RIM101 family and present in an identical position of the last finger alpha
      helix of Drosophila Cubitus interruptus, where it is also involved in nuclear
      localisation. We propose that PacC and Gli/Ci zf-DBDs belong to a subclass of
      these domains characterised by possession of a pair of conserved Trp residues
      involved in the interaction between the two most N-terminal fingers and the
      presence of an NLS in the alpha-helix of the most C-terminal finger. Loss of PacC
      nuclear localisation resulting from His142Leu (beta-strand) and Phe151Ser
      (hydrophobic core) substitutions in finger 3 suggests that its folding is
      required for NLS function. Overlap of DNA binding and NLS may aid release of PacC
      from its cognate importer(s) upon nuclear translocation, as suggested for zinc
      binuclear cluster proteins.

PMID- 14636597
TI  - A structure-based anatomy of the E.coli metabolome.
AB  - The Escherichia coli metabolome has been characterised using the two-dimensional
      structures of 745 metabolites, obtained from the EcoCyc and KEGG databases.
      Physicochemical properties of the metabolome have been calculated to provide an
      overview of this set of cognate ligands. A library of fragments commonly found
      among these molecules has been employed to reveal the main constituents of
      metabolites, and to assist a broad classification of the metabolome into
      biochemically relevant classes. Fragment-based fingerprints reveal the metabolome
      as a continuum in the two-dimensional structural space, where clusters of
      molecules sharing similar scaffolds can be identified, but are generally
      overlapping. Nucleotide, carbohydrate and amino acid-like molecules are the most
      prominent, but at high levels of similarity, a more detailed classification is
      possible. Classification schemes for the metabolome are a promising tool for
      understanding the chemical diversity of the metabolome. When used in conjunction
      with existing classifications of the proteome, they can help to elucidate the
      binding preferences and promiscuity of proteins and their cognate substrates.

PMID- 14636596
TI  - The crystal structure of the gene targeting homing endonuclease I-SceI reveals
      the origins of its target site specificity.
AB  - The I-SceI homing endonuclease enhances gene targeting by introducing double
      strand breaks at specific chromosomal loci, thereby increasing the recombination
      frequency. Here, we report the crystal structure of the enzyme complexed to its
      DNA substrate and Ca(2+) determined at 2.25A resolution. The structure shows the
      prototypical beta-saddle of LAGLIDADG homing endonucleases that is contributed by
      two pseudo-symmetric domains. The high specificity of I-SceI is explained by the
      large number of protein-DNA contacts, many that are made by a long beta-hairpin
      loop that reaches into the major groove of the DNA. The DNA minor groove is
      compressed at the catalytic center, bringing the two scissile phosphodiester
      bonds into close proximity. The protein-Ca(2+)-DNA structure shows the protein
      bound to its DNA substrate in a pre-reactive state that is defined by the
      presence of two asymmetric active sites, one of which appears poised to first
      cleave the DNA bottom strand.

PMID- 14636598
TI  - Structure of an influenza neuraminidase-diabody complex by electron
      cryomicroscopy and image analysis.
AB  - The structure of a complex between a bivalent diabody and its antigen, influenza
      neuraminidase, has been determined by electron cryomicroscopy of single particles
      and image analysis. A three-dimensional reconstruction has been interpreted in
      terms of high-resolution X-ray models of the component proteins. The complex
      consists of two neuraminidase tetramers cross-linked by four diabodies with 422
      point symmetry. The structure and symmetry of the complex is determined uniquely
      by packing constraints consistent with the maximum possible number of diabody
      cross-links. Diabodies may provide a useful approach to the structure
      determination of small proteins by incorporating the proteins into large
      symmetric complexes followed by single-particle electron microscopy.

PMID- 14636599
TI  - Expressed murine and human CDR-H3 intervals of equal length exhibit distinct
      repertoires that differ in their amino acid composition and predicted range of
      structures.
AB  - Immunoglobulin junctional diversity is concentrated in the third complementarity
      determining region of the heavy chain (CDR-H3), which often plays a dominant role
      in antigen binding. The range of CDR-H3 lengths in mouse is shorter than in
      human, and thus the murine repertoire could be presumed to be a subset of the
      human one. To test this presumption, we analyzed 4751 human and 2170 murine
      unique, functional, published CDR-H3 intervals. Although tyrosine, glycine, and
      serine were found to predominate in both species, the human sequences contained
      fewer tyrosine residues, more proline residues, and more hydrophobic residues
      (p<0.001, respectively). While changes in amino acid utilization as a function of
      CDR-H3 length followed similar trends in both species, murine and human CDR-H3
      intervals of identical length were found to differ from each other. These
      differences reflect both divergence of germline diversity and joining gene
      sequence and somatic selection. Together, these factors promote the production of
      a rather uniform repertoire in mice of tyrosine-enriched CDR-H3 loops with
      stabilized hydrogen bond-ladders versus a much more diverse repertoire in human
      that contains CDR-H3 loops sculpted by the presence of intra-chain disulfide
      bonds due to germline-encoded cysteine residues as well as the enhanced presence
      of somatically generated proline residues that preclude hydrogen bond ladder
      formation. Thus, despite the presumed need to recognize a similar range of
      antigen epitopes, the murine CDR-H3 repertoire is clearly distinct from its human
      counterpart in its amino acid composition and its predicted range of structures.
      These findings represent a benchmark to which CDR-H3 repertoires can be compared
      to better characterize and understand the shaping of the CDR-H3 repertoire over
      evolution and during immune responses. This information may also be useful for
      the design of species-specific CDR-H3 sequences in synthetic antibody libraries.

PMID- 14636600
TI  - Structural characterization of the 69 nucleotide potato spindle tuber viroid left
      terminal domain by NMR and thermodynamic analysis.
AB  - The 69 nucleotide left-terminal domain (T(L)) of the potato spindle tuber RNA
      viroid (PSTVd) constitutes one of its five structural elements. Due to a twofold
      complementary sequence repeat, two possible conformations are proposed for the
      T(L) secondary structure; an elongated-rod and a bifurcated form. In the present
      study, two T(L) mutants were designed that remove the symmetry of the sequence
      repeats and ensure that either the bifurcated or the elongated-rod conformation
      is thermodynamically favored. Imino 1H and 15N resonances were assigned for both
      mutants and the native T(L) domain based on 1H-1H NOESY and heteronuclear 1H-15N
      HSQC high-resolution NMR spectra. The NMR secondary structure analysis of all
      constructs establishes unambiguously the elongated-rod form as the secondary
      structure of the native T(L) domain. Temperature-gradient gel electrophoresis and
      UV melting experiments corroborate these results. A combined secondary structure
      and sequence analysis of T(L) domains of other Pospiviroidae family members
      indicates that the elongated-rod form is thermodynamically favored for the vast
      majority of these viroids.

PMID- 14636601
TI  - The Sir4 C-terminal coiled coil is required for telomeric and mating type
      silencing in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae Sir4p plays important roles in silent chromatin at
      telomeric and silent mating type loci. The C terminus of Sir4p (Sir4CT) is
      critical for its functions in vivo because over-expression or deletion of Sir4CT
      fragments disrupts normal telomeric structure and abolishes the telomere position
      effect. The 2.5A resolution X-ray crystal structure of an Sir4CT fragment (Sir4p
      1217-1358) reveals a 72 residue homodimeric, parallel coiled coil, burying an
      extensive 3600A(2) of surface area. The crystal structure is consistent with
      results of protein cross-linking and analytical ultracentrifugation results
      demonstrating that Sir4CT exists as a dimer in solution. Disruption of the coiled
      coil in vivo by point mutagenesis results in total derepression of telomeric and
      HML silent mating marker genes, suggesting that coiled coil dimerization is
      essential for Sir4p-mediated silencing. In addition to the coiled coil
      dimerization interface (Sir4CC interface), a crystallographic interface between
      pairs of coiled coils is significantly hydrophobic and buries 1228A(2) of surface
      area (interface II). Remarkably, interface II mutants are deficient in telomeric
      silencing but not in mating type silencing in vivo. However, point mutants of
      interface II do not affect the oligomerization state of Sir4CT in solution. These
      results are consistent with the hypothesis that interface II mimics a protein
      interface between Sir4p and one of its protein partners that is essential for
      telomeric silencing but not mating type silencing.

PMID- 14636602
TI  - Uncovering network systems within protein structures.
AB  - Traditionally, proteins have been viewed as a construct based on elements of
      secondary structure and their arrangement in three-dimensional space. In a
      departure from this perspective we show that protein structures can be modelled
      as network systems that exhibit small-world, single-scale, and to some degree,
      scale-free properties. The phenomenological network concept of degrees of
      separation is applied to three-dimensional protein structure networks and reveals
      how amino acid residues can be connected to each other within six degrees of
      separation. This work also illuminates the unique features of protein networks in
      comparison to other networks currently studied. Recognising that proteins are
      networks provides a means of rationalising the robustness in the overall three
      dimensional fold of a protein against random mutations and suggests an
      alternative avenue to investigate the determinants of protein structure, function
      and folding.

PMID- 14636603
TI  - The PDB is a covering set of small protein structures.
AB  - Structure comparisons of all representative proteins have been done. Employing
      the relative root mean square deviation (RMSD) from native enables the assessment
      of the statistical significance of structure alignments of different lengths in
      terms of a Z-score. Two conclusions emerge: first, proteins with their native
      fold can be distinguished by their Z-score. Second and somewhat surprising, all
      small proteins up to 100 residues in length have significant structure alignments
      to other proteins in a different secondary structure and fold class; i.e. 24.0%
      of them have 60% coverage by a template protein with a RMSD below 3.5A and 6.0%
      have 70% coverage. If the restriction that we align proteins only having
      different secondary structure types is removed, then in a representative
      benchmark set of proteins of 200 residues or smaller, 93% can be aligned to a
      single template structure (with average sequence identity of 9.8%), with a RMSD
      less than 4A, and 79% average coverage. In this sense, the current Protein Data
      Bank (PDB) is almost a covering set of small protein structures. The length of
      the aligned region (relative to the whole protein length) does not differ among
      the top hit proteins, indicating that protein structure space is highly dense.
      For larger proteins, non-related proteins can cover a significant portion of the
      structure. Moreover, these top hit proteins are aligned to different parts of the
      target protein, so that almost the entire molecule can be covered when combined.
      The number of proteins required to cover a target protein is very small, e.g. the
      top ten hit proteins can give 90% coverage below a RMSD of 3.5A for proteins up
      to 320 residues long. These results give a new view of the nature of protein
      structure space, and its implications for protein structure prediction are
      discussed.

PMID- 14636604
TI  - Inter-helical hydrogen bond formation during membrane protein integration into
      the ER membrane.
AB  - Recent work has shown that efficient di- or trimerization of hydrophobic
      transmembrane helices in detergent micelles or lipid bilayers can be driven by
      inter-helix hydrogen bonding involving polar residues such as Asn or Asp. Using
      in vitro translation in the presence of rough microsomes of a model integral
      membrane protein, we now show that the formation of so-called helical hairpins,
      two tightly spaced transmembrane helices connected by a short loop, can likewise
      be promoted by the introduction of Asn-Asn or Asp-Asp pairs in a long
      transmembrane hydrophobic segment. These observations suggest that inter-helix
      hydrogen bonds can form within the context of the Sec61 translocon in the
      endoplasmic reticulum, implying that hydrophobic segments in a nascent
      polypeptide chain in transit through the Sec61 channel have immediate access to a
      non-aqueous subcompartment within the translocon.

PMID- 14636605
TI  - Stabilization of a tetrameric malate dehydrogenase by introduction of a disulfide
      bridge at the dimer-dimer interface.
AB  - Malate dehydrogenase (MDH) from the moderately thermophilic bacterium
      Chloroflexus aurantiacus (CaMDH) is a tetrameric enzyme, while MDHs from
      mesophilic organisms usually are dimers. To investigate the potential
      contribution of the extra dimer-dimer interface in CaMDH with respect to thermal
      stability, we have engineered an intersubunit disulfide bridge designed to
      strengthen dimer-dimer interactions. The resulting mutant (T187C, containing two
      187-187 disulfide bridges in the tetramer) showed a 200-fold increase in half
      life at 75 degrees C and an increase of 15 deg. C in apparent melting temperature
      compared to the wild-type. The crystal structure of the mutant (solved at 1.75 A
      resolution) was essentially identical with that of the wild-type, with the
      exception of the added inter-dimer disulfide bridge and the loss of an aromatic
      intra-dimer contact. Remarkably, the mutant and the wild-type had similar
      temperature optima and activities at their temperature optima, thus providing a
      clear case of uncoupling of thermal stability and thermoactivity. The results
      show that tetramerization may contribute to MDH stability to an extent that
      depends strongly on the number of stabilizing interactions in the dimer-dimer
      interface.

PMID- 14636606
TI  - Sequence, structure and energetic determinants of phosphopeptide selectivity of
      SH2 domains.
AB  - Here, we present an approach for the prediction of binding preferences of members
      of a large protein family for which structural information for a number of family
      members bound to a substrate is available. The approach involves a number of
      steps. First, an accurate multiple alignment of sequences of all members of a
      protein family is constructed on the basis of a multiple structural superposition
      of family members with known structure. Second, the methods of continuum
      electrostatics are used to characterize the energetic contribution of each
      residue in a protein to the binding of its substrate. Residues that make a
      significant contribution are mapped onto the protein sequence and are used to
      define a "binding site signature" for the complex being considered. Third,
      sequences whose structures have not been determined are checked to see if they
      have binding-site signatures similar to one of the known complexes. Predictions
      of binding affinity to a given substrate are based on similarities in binding
      site signature. An important component of the approach is the introduction of a
      context-specific substitution matrix suitable for comparison of binding-site
      residues. The methods are applied to the prediction of phosphopeptide selectivity
      of SH2 domains. To this end, the energetic roles of all protein residues in 17
      different complexes of SH2 domains with their cognate targets are analyzed. The
      total number of residues that make significant contributions to binding is found
      to vary from nine to 19 in different complexes. These energetically important
      residues are found to contribute to binding through a variety of mechanisms,
      involving both electrostatic and hydrophobic interactions. Binding-site
      signatures are found to involve residues in different positions in SH2 sequences,
      some of them as far as 9A away from a bound peptide. Surprisingly, similarities
      in the signatures of different domains do not correlate with whole-domain
      sequence identities unless the latter is greater than 50%. An extensive
      comparison with the optimal binding motifs determined by peptide library
      experiments, as well as other experimental data indicate that the similarity in
      binding preferences of different SH2 domains can be deduced on the basis of their
      binding-site signatures. The analysis provides a rationale for the empirically
      derived classification of SH2 domains described by Songyang & Cantley, in that
      proteins in the same group are found to have similar residues at positions
      important for binding. Confident predictions of binding preference can be made
      for about 85% of SH2 domain sequences found in SWISSPROT. The approach described
      in this work is quite general and can, in principle, be used to analyze binding
      preferences of members of large protein families for which structural information
      for a number of family members is available. It also offers a strategy for
      predicting cross-reactivity of compounds designed to bind to a particular target,
      for example in structure-based drug design.

PMID- 14636607
TI  - Extra-oral craniofacial endosseous implants and radiotherapy.
AB  - This paper discusses the use of extra-oral endosseous craniofacial implant
      (EOECI) therapy in irradiated bone. The survival rate of EOECIs in irradiated
      bone is reviewed and the controversy over the optimal time prior to place
      implants is described. The advantages and disadvantages of pre- and post-implant
      radiotherapy are addressed. The EOECI rehabilitation and osteoradionecrosis and
      the evidence of the potential role of hyperbaric oxygen are reviewed. Strategies
      for improving the clinical outcome of EOECIs are suggested.

PMID- 14636608
TI  - Evaluation of swallowing function after intraoral soft tissue reconstruction with
      microvascular free flaps.
AB  - This study assessed swallowing function after tumour resection and reconstruction
      utilizing free vascularized flap closures in patients with oral cancer.
      Swallowing function was evaluated postoperatively in 23 patients (21 men and 2
      women) who had undergone reconstruction with either a lateral upper arm free flap
      (LUFF, n=16) or a radial forearm free flap (RFFF, n=7). Videofluoroscopy was used
      to assess tongue mobility and abnormalities of swallowing function. All patients
      who underwent reconstruction with LUFF or RFFF free flaps had decreased tongue
      mobility, except for the tip of the tongue. Patients who underwent anterior or
      posterior resection had greater decreases in tongue mobility than those who
      underwent medial resection. Swallowing impairment was similar in patients with
      LUFFs and those with RFFFs. Anterior resection of the oral cavity had a
      significant negative effect on swallowing function. Silent aspiration occurred in
      five patients. In conclusion the resection site affected swallowing function, but
      the type of flap did not, in patients with oral carcinoma, who underwent tumour
      resection with reconstruction

PMID- 14636609
TI  - Are collimated low-dose digital radiographs valid for performing Delaire's
      architectural analysis?
AB  - Computed radiography (CR) provides the dynamic exposure range to reveal objects
      in film areas exposed by very low X-ray exposure. Conventional cephalometric
      radiographs are normally beam limited to the facial skeleton. The cranial vault
      and cervical vertebra are collimated and only exposed by extra-focal radiation
      and scatter. We hypothesize that, on conventional cephalometric radiographs
      obtained with CR, image data of collimated film areas can be enhanced for
      reliable performance of Delaire's cephalometric analysis of the entire skull.
      Therefore the aim of the present study was to compare the reproducibility of
      landmark placement on normal and underexposed film areas of CR images. Intra- and
      inter-observer reproducibility of landmark identification was evaluated on 200
      randomly selected radiographs by calculating the error radius of repeated
      landmark placements. A paired-samples t-test revealed differences (P< 0.001)
      between intra- and inter-observer reproducibility. Intra-observer accuracy was
      influenced (P< 0.001) by variability of suture obliteration (bregma).
      Identification of landmarks in areas of extra-focal radiation showed no
      difference (P> 0.05) from that of landmarks inside the normally exposed area. CR
      offers the opportunity to perform of a full cranial analysis on a cephalometric
      radiograph collimated to the facial region.

PMID- 14636610
TI  - A retrospective study of the costochondral graft in TMJ reconstruction.
AB  - A retrospective review of 76 costochondral grafts (57 patients) was undertaken to
      determine outcome with respect to the extent of previous surgery (none, disc
      surgery or soft tissue graft, alloplastic disc, alloplastic joint, previous
      graft) and to initial and preoperative diagnosis. The minimum follow up period
      was 2 years and for each patient both subjective (pain and dietary interference
      scores) and objective (interincisal distance) data was recorded. Collectively
      there was improvement in pain (mean 6.7 to 3.5) and diet (mean 2.2 to 3.0) scores
      with a moderate increase in interincisal distance (mean 21 to 24mm). In patients
      with no previous surgery, arthritic disease or congenital deformity the
      costochondral graft performed well but in patients with previous alloplastic
      discs and/or total joints the results were less predictable. A preoperative
      diagnosis of ankylosis was associated with a high complication and further
      surgery rate suggesting caution in this group of patients.

PMID- 14636611
TI  - Mandibular buccal bifurcation cyst: enucleation without extraction.
AB  - The mandibular buccal bifurcation cyst (MBBC) is a cystic lesion, which occurs on
      the buccal surface of the permanent mandibular first molar in children around 6-8
      years old. Treatment of the cyst has been controversial: extraction of the
      involved tooth and enucleation of the cyst, or only enucleation, without
      extraction. The aim of this article is to familiarize oral and maxillofacial
      surgeons with this entity and the appropriate treatment approach. The diagnostic
      features of MBBC are described and the treatment approach in five patients with a
      total of seven cysts is presented. Two cases were identified in identical twins.
      Enucleation of the cyst without extraction of the involved tooth is the treatment
      of choice when the available data and experience in treating MBBC are considered.

PMID- 14636612
TI  - The radial forearm flap as a carrier for the osteocutaneous fibula graft in
      mandibular reconstruction.
AB  - According to the concept of a free flap carrier we transferred an osteocutaneous
      fibula graft after microanastomosis to a pedicled radial forearm flap for
      reconstruction of the lower face in a patient with a total occlusion of the left
      and a subtotal occlusion of the right common carotid artery. The fibula was
      osteotomized in three segments to form the new mandible, and the skin paddle was
      placed extraorally. An external fixation device was connected to the radial bone,
      and a halo frame was fixed to the skull, and the forearm was thus stabilized
      rigidly in a suitable position. After 2 weeks, serial occlusion of the pedicle
      was begun twice daily. Blood flow and haemoglobin oxygenation of the skin paddle
      were measured by laser Doppler flowmetry and photometry. At the 14th day of
      ischaemic preconditioning, the flap could tolerate 3h of occlusion. Then the
      carrier vessels and the forearm flap were excised. The flap survived completely
      based on neovascularization from the recipient site.

PMID- 14636613
TI  - The role of ultrasound in monitoring reconstruction of mandibular continuity
      defects using osteogenic protein-1 (rhOP-1).
AB  - Introducing bone bioengineering concepts in craniofacial surgery demands
      development of novel imaging strategies, which overcome the shortcomings of
      radiography such as exposure to ionizing radiation. This study is aimed to
      investigate the usefulness of ultrasonography (US) in monitoring reconstruction
      of continuity osteoperiosteal mandibular defects in sheep using rhOP-1. The study
      was conducted on six adult sheep in which a critical size defect was created at
      the body of the mandible and was reconstructed using rhOP-1 with type-I collagen
      as a carrier. Ultrasound images were used to assess onset of bone formation,
      contour, and surface topography. The results were then compared to corresponding
      plain radiographs and to post-mortem observations. US showed bone union in all
      the subjects that concurred with radiographic and post-mortem examinations. US
      was superior to plain radiography in monitoring early events of ossification.
      However, it was relatively less efficient in describing the contour of the newly
      formed bone. It was possible to describe the pattern of bone formation and the
      dynamic changes in contour and surface topography via US during the follow-up
      period. In experienced hands, ultrasonography can offer valuable information
      about bone healing comparable with those obtained by plain radiography. US may
      replace plain radiography in becoming a routinely used tool for monitoring bone
      healing in selected sites of the craniofacial skeleton.

PMID- 14636614
TI  - Bone formation after implantation of autolysed antigen extracted allogeneic bone
      in ovariectomized rabbits.
AB  - This study was undertaken to evaluate the bone formation response to AAA bone in
      healthy and oestrogen deficient animals. Seventeen young healthy New Zealand
      female rabbits were used. Nine rabbits were subjected to ovariectomy and the
      remaining eight were sham-operated. Four weeks after ovariectomy standardized
      round cavities, 5mm in diameter, were made medially in the cortical part of each
      proximal tibia. To half of the cavities autolysed antigen-extracted allogeneic
      AAA bone granules were added. After another 8 weeks the animals were sacrificed
      and sections of the tibial experimental areas were obtained. These were studied
      in light microscopy and the bone and non-bone areas were measured with computer
      support. The study showed that the addition of a bone inductive substance such as
      AAA bone enhances bone formation also in oestrogen deficient animals.

PMID- 14636615
TI  - Predictive value of immunohistochemical thymidylate synthase expression for
      histological response to Tegafur/Uracil (UFT) in oral squamous cell carcinoma.
AB  - Thymidylate synthase (TS), an enzyme involved in the DNA synthesis, is a critical
      target for fluoropyrimidines. We investigated the relationship between the level
      of tumoural TS expression and response to tegafur/uracil (UFT) in 26 patients
      with oral squamous cell carcinoma. The patients received peroral administration
      of UFT alone preoperatively. In biopsy specimens, TS expression level was
      assessed by the immunohistochemical staining and graded as 1+, 2+ or 3+ according
      to the frequency of strongly-stained tumour cells. Out of 26 tumours, 10 (38.5%),
      10 (38.5%) and 6 (23.1%) cases were categorized as 1+, 2+ and 3+, respectively.
      The response to UFT was histologically evaluated by a grading system according to
      the extent of degenerative or necrotic cancer cells in surgical specimens.
      Results showed patients with the lower TS expression had the higher response and
      there was a statistically significant association between TS expression and
      response to UFT (P=0.031). This finding suggests that TS expression is a
      predictor of chemosensitivity to UFT in oral squamous cell carcinomas.

PMID- 14636616
TI  - Regional thickness of parietal bone in Korean adults.
AB  - To clarify the clinical utility of the parietal bone graft in maxillofacial
      reconstruction, we performed an anatomical study by measuring the regional
      thickness of the parietal bone in 47 Korean adult dry skulls. Before sectioning
      of the calvaria, the appropriate anatomical landmarks were marked on each
      specimen. We measured the total thickness of the parietal bone, and the thickness
      of the outer and inner cortical plates at various points in each section of
      parietal bones using a digital caliper under the stereomicroscope. The total
      thickness of the parietal bone ranged from 5.04mm to 7.17mm, and there was no
      statistical difference in the total thickness of the parietal bone on the same
      points bilaterally. The parietal bone tended to be thicker toward the lambda
      point than at the coronal suture area. On the other hand, the outer plate of
      parietal bone was thickest at the point nearest to the coronal suture, and the
      inner plate proved thickest at the posteromedial area. In conclusion, this study
      showed that the better donor site of the parietal bone for maxillofacial
      reconstruction is located at its more posterior and medial area.

PMID- 14636617
TI  - Locating broken dental needles.
AB  - Broken dental needles are a rare event. They are difficult to find and remove. We
      report two cases in which broken needles were located using a simple stereotactic
      method with the aid of an image intensifier.

PMID- 14636618
TI  - Resection and replacement of the carotid artery in metastatic head and neck
      cancer: literature review and case report.
AB  - Metastases of advanced tumours of the oral cavity sometimes affect the cervical
      segments of the carotid arteries. The situation is worse in the 5-10% of cases in
      which the metastasis involves the common or internal carotid to such an extent
      that resection and replacement of the artery become necessary. Following
      clinical, CT/NM, and angiographic examinations, a surgical plan for the resection
      and reconstruction of the affected vascular segment is formulated. In preparing a
      treatment plan, emphasis must be placed on the expected quality of life, and
      careful consideration must be given to the extent of the operation.A survey of
      the international literature reveals that the reported mean 1-year complaint free
      survival rate after resection and reconstruction varies between 0 and 44%. In our
      experience, the wall of the carotid vessels is very resistant to tumour invasion
      in a large majority of patients. When radical surgery and reconstruction are
      carried out in the same session, does this increase the long-term cure rate and
      lengthen patient survival? A number of authors agree that radical interventions
      do not alter the survival indices significantly, but may improve the quality of
      life and regional control of the disease. The controversy over this topic is
      illustrated by means of a case report.

PMID- 14636619
TI  - Gadolinium an alternative contrast agent for sialography in patients with iodine
      sensitivity.
AB  - The use of iodinated contrast material in radiography is contraindicated in
      patients with known iodine sensitivity and such patients may present a management
      dilemma. The successful use of gadolinium in contrast sialography is described.

PMID- 14636620
TI  - Metal fragment in the temporomandibular joint: a case report.
AB  - A 56-year-old woman was referred for severe pain and restricted jaw movements
      with a duration of more than 10 years. In the early 1990s a discectomy on the
      left side had been performed where the disc was extirpated and replaced with a
      polymeric implant. Due to infection and pain the implant was removed about 2
      months later. In the 10-year period thereafter she suffered pain from the joint,
      pain from the left ear, tinnitus and restricted mouth opening.A computer
      tomography scan revealed a foreign body, approximately 4mm in size, situated in
      the medial part of the glenoid fossa. The metallic foreign body was surgically
      removed. The pain from her left temporomandibular joint decreased and the mouth
      opening capacity increased. Patch-testing showed that the patient had a potential
      for contact allergy to nickel, chromium and cobalt. The foreign body was most
      probably a fractured tip of a surgical awl. Energy dispersive X-ray analysis
      revealed that the fragment consisted of iron and chromium. The instrument
      fragment could have caused the symptoms either by an allergic reaction or a
      direct mechanical effect.

PMID- 14636622
TI  - Eccrine spiradenoma of the ear: case report.
AB  - A case of eccrine spiradenoma of the left pinna is described. To the best of our
      knowledge, this is the first report regarding this site. The treatment was a
      surgical excision in safe margins. This rare benign tumour should be considered
      for the differential diagnosis of solitary or multiple soft tissue lesions of the
      head and neck.

PMID- 14636621
TI  - Bone wax as a cause of a foreign body granuloma in a cranial defect: a case
      report.
AB  - Bone wax was used to stop bleeding of the diploic vessels after harvesting
      cranial bone for reconstruction of an orbital floor defect. After five months a
      fistula in the overlying skin of the donor site appeared and was eventually
      surgically explored. Remnants of bone wax and surrounding inflammatory tissue
      were removed and the fistula was excised. Histological examination revealed a
      foreign body granuloma. The use of bone wax and possible alternative local
      haemostatic agents and their complications are discussed.

PMID- 14636623
TI  - Solitary plasmacytoma of the mandible in a renal transplant recipient.
AB  - A solitary plasmacytoma occurring in the mandible of a 15-year-old Korean male 6
      years after renal transplantation is reported. The tumour presented as a
      hyperplastic gingival overgrowth in the right madibular molar area. Histology and
      immunohistochemistry revealed plasmacytoma and monoclonality of the kappa chain
      and IgG. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) showed
      positive signals in the tumour cells. The tumour regressed after reducing the
      immunosuppressive agents with concurrent radiotherapy. The patient remains in a
      stable condition with normal renal functions after 7 years without recurrence.
      This case confirms that Epstein-Barr virus associated B-lymphoproliferative
      disorders are still a major complication of immunosuppression.

PMID- 14636626
TI  - Evolution of the role of GnRH in animal (Metazoan) biology.

PMID- 14636627
TI  - Crustacean neuropeptide genes of the CHH/MIH/GIH family: implications from
      molecular studies.
AB  - The crustacean eyestalk CHH/MIH/GIH gene family represents a unique group of
      neuropeptide originally identified in crustaceans. These neuropeptides shared a
      high degree of amino acid identity, and the conservation of cysteine residues at
      the same relative positions. Based on their biological, biochemical, and
      molecular properties, they can be divided into the CHH and MIH subtypes with two
      major members in each subtype. In the shrimp, the CHH-subtypes can be divided
      into two forms (CHH-A and CHH-B). The CHH-A gene also comprises several isoforms
      which shared a high overall sequence identity. Although the MIH subtypes are
      postulated to have evolved from the CHH subtypes, the number of major MIH
      subtypes in each species has yet to be confirmed. While most of the genes consist
      of the basic plan of three exons and two introns, other alternative spliced
      variants have recently been described. Moreover, these alternative forms are
      usually expressed in non-eyestalk tissues. These findings suggest that these
      neuropeptides may have a broader spectrum of functions in crustaceans. The
      results from phylogenetic analysis suggest that the evolution of this group of
      neuropeptides occurs in a manner similar is to the gene duplication and mutation
      events hypothesized for the origin of the prolactin and growth hormone gene
      family of the vertebrate pituitary system.

PMID- 14636628
TI  - Intratesticular signals for progression of germ cell stages in vertebrates.
AB  - The mechanisms underlying the complexity of spermatogenesis and spermiogenesis
      have deeply been studied in recent years. Transgenic animals, gene-targeting
      techniques, and lower vertebrate animal models have led to the discovery of some
      of the intratesticular signals involved in germ cell progression. This review
      wish to give the state of the art about it with particular emphasis on the
      comparative approach.

PMID- 14636629
TI  - Immunocytochemical localization of substance P in the adrenal gland of Podarcis
      sicula (Reptilia, Lacertidae): evidence for its involvement in the modulation of
      adrenal activity.
AB  - The occurrence of substance P (SP) immunoreactivity was investigated in the
      adrenal gland of the lizard Podarcis sicula by ABC immunocytochemical technique:
      SP-immunoreactivity was present in both adrenaline and noradrenaline cells, in
      ganglion cells and nerve fibers in the connective capsule surrounding the gland.
      The involvement of substance P in the modulation of pituitary-interrenal axis was
      studied in vivo by intraperitoneal injections of SP. The effects were estimated
      by means of the morphological and morphometrical features of the tissues, as well
      as the plasma levels of adrenocorticotropic hormone (ACTH), corticosterone and
      catecholamines, adrenaline and noradrenaline. Substance P (0.07 mg/100 g body wt)
      decreased ACTH plasma levels and raised corticosterone release from steroidogenic
      tissue, that showed clear signs of stimulation. In the chromaffin tissue, the
      decrease in the number of noradrenaline cells, and the increase in the number of
      adrenaline cells, lowered numeric noradrenaline/adrenaline cell ratio. Moreover,
      an increase in adrenaline plasma level and a decrease in noradrenaline plasma
      level were found. The results suggest that (1) also in Reptiles as in other
      Vertebrates, SP may affect pituitary-adrenal axis activity, and (2) the
      chromaffin cells may be involved in the paracrine control of steroidogenic
      activity.

PMID- 14636630
TI  - Age-dependent changes in the response of the stomach to thyroidal signaling in
      developmentally arrested larval summer flounder.
AB  - Thyroid-dependent stomach development occurs between approximately 35 and 50 days
      post-hatch (dph) in laboratory-reared summer flounder larvae. The process can be
      blocked by thiourea (TU), and TU effects are reversed by exogenous thyroxine
      (T4). To establish whether a window of sensitivity exists for T4-dependent
      gastric development, we arrested development of larvae with 0.39 mM TU given from
      26 to 61dph, and measured weekly the developmental response of the stomach to 13
      nM T4 for 0, 2, or 7 days. We examined cell proliferation in surface epithelium,
      gastric glands, and connective tissue, pepsinogen immunoreactivity in gastric
      glands, and Ulex Europaeus I (UEA I) lectin staining of gastric mucous neck
      cells, indicative of mucous content. In 26-47dph larvae, cell proliferation was
      increased 5- to 10-fold in all cell types after 2 days in T4, and returned to
      pretreatment values by 7 days of treatment. In 54dph fish, however, the
      proliferative response of gastric gland and surface epithelial cells decreased
      significantly from that of younger fish, while that of connective tissue was
      unchanged. For the differentiation markers, T4-induced mucous content increased
      at 54dph, but not in older fish, while pepsinogen induction was not different at
      any of the ages tested. The age interval between 47 and 54dph corresponds with
      the completion of gastric development in spontaneously metamorphosing larvae. The
      findings suggest that a critical window exists for the mitogenic actions of T4 in
      epithelial cells, but not for connective tissue cells, whereas no critical period
      was found for markers of differentiation.

PMID- 14636631
TI  - Expression of a biologically active recombinant follicle stimulating hormone of
      Japanese Eel Anguilla japonica using methylotropic yeast, Pichia pastoris.
AB  - In the Japanese eel Anguilla japonica, the administration of exogenous GTH is
      necessary for the artificial induction and completion of gonadal maturation due
      to its GTH deficiency under captive conditions. The isolation of native eel GTH
      has not been accomplished, which has made it difficult to fully elucidate the
      biological functioning of the two GTHs (FSH and LH) in eel. In this study, we
      attempted to produce a recombinant Japanese eel GTH (rjeFSH) having biological
      activity using methylotrophic yeast, Pichia pastoris in order to gain more
      understanding of the functioning of GTH in this species. An expression vector in
      which jeFSHbeta and GTHalpha subunit cDNAs were tandemly connected was
      constructed. P. pastoris was transformed with the vector, and rjeFSH was
      expressed. The rjeFSH thus expressed was detected by Western blot analysis. The
      glycoprotein fraction of the yeast culture supernatant was separated by native
      PAGE, and a band showed positive reaction with anti-GTHalpha and FSHbeta antisera
      similarly, suggesting that both subunits are associated. After deglycosylation,
      both subunits were decreased in molecular mass, indicating that rjeFSH was
      glycosylated. In in vitro assay, rjeFSH stimulated the release of testosterone
      and 11-ketotestosterone from immature eel testis, whereas release was not
      stimulated in maturing eel testis. This is the first report investigating the
      biological activity of eel GTH using the recombinant eel FSH.

PMID- 14636632
TI  - In vivo implants of beta-sitosterol cause reductions of reactive cholesterol
      pools in mitochondria isolated from gonads of male goldfish (Carassius auratus).
AB  - beta-Sitosterol, a phytosterol found in high concentrations in pulp mill
      effluents, has been proposed as one of the causative agents for steroid
      depressions observed in fish exposed to pulp mill effluents. Previous studies
      have suggested a cholesterol-mediated mechanism; however, it is unknown how beta
      sitosterol depresses gonadal steroidogenesis. In this study, adult male goldfish
      (Carassius auratus) were exposed for 24-31 days to beta-sitosterol (55% of a
      phytosterol mixture or 96% pure; 150 microg/g; Silastic implant) after which
      gonadal mitochondria were isolated. Pregnenolone production, an indicator of the
      size of the pool of reactive cholesterol, was then measured in the isolated
      mitochondria. Sterol exposure did not affect P450 side-chain cleavage enzyme
      (converts cholesterol to pregnenolone) activity but did decrease the size of the
      mitochondrial pool of reactive cholesterol, suggesting beta-sitosterol is
      impeding cholesterol transfer across the mitochondrial membrane. This finding is
      supported by the observation that 25-hydroxycholesterol, which passes through
      mitochondrial membranes without need for a membrane transporter, restores beta
      sitosterol-induced reductions in pregnenolone production.

PMID- 14636633
TI  - Early decrease of proopiomelanocortin but not neuropeptide Y mRNA expression in
      the mediobasal hypothalamus of the ewe, during the estradiol-induced preovulatory
      LH surge.
AB  - In sheep, the mediobasal hypothalamus (MBH) has been shown to be the primary
      central site of estradiol (E2) action that induces both the preovulatory surge
      and sexual behaviour. However, the nature of the neurotransmitters or
      neuromodulators synthesized in the MBH during E2 stimulation remains to be
      clearly defined. After the cloning of the ovine cDNA sequences and using in situ
      hybridization, hypothalamic proopiomelanocortin (POMC), and preproneuropeptide Y
      (preproNPY) mRNA expression was studied in ovariectomized ewes that received a
      sequential treatment of progesterone and E2. As we showed that an exposition to
      E2 only for 4h well in advance on the LH surge onset is sufficient to induce the
      preovulatory surge and estrous behaviour, mRNA expression was evaluated in ewes
      treated with 6x30-mm E2 implants (experimental group) or with empty implants
      (control group) and slaughtered 4h after the start of the E2 treatment. Our
      results demonstrate that this short E2 treatment significantly decreased both the
      mean number of silver grains per POMC-containing cell (35%) and the mean number
      of POMC-cells (38%) in the ovine infundibular nucleus, whereas the treatment had
      no effect on preproNPY mRNA expression. These observations suggest that a
      reduction of POMC gene transcription could participate to the early neural
      mechanism of E2 feedback.

PMID- 14636634
TI  - Altered steroid metabolism in several teleost species exposed to endocrine
      disrupting substances in refuse dump leachate.
AB  - Endocrine disruption associated with reproductive failure has been reported
      previously in female perch (Perca fluviatilis) and roach (Rutilus rutilus) from
      Lake Molnbyggen in Sweden and in female brook trout (Salvelinus fontinalis) from
      Vadbacken, a stream emptying into Molnbyggen. Both Molnbyggen and Vadbacken have
      been contaminated by toxic leachate from a municipal refuse dump. In this study,
      female perch were caught in Molnbyggen and the reference lake, Lake Djursjon, to
      further investigate the endocrine mechanism behind the significant numbers of
      sexually immature (SIM) female perch in Molnbyggen. Blood plasma analysis of
      progesterone (P), 17alpha-hydroxyprogesterone (17alpha-OHP), testosterone (T),
      and 17beta-oestradiol (E2), as well as analysis of brain aromatase activity
      (P450arom), were carried out. The exceptional high numbers of SIM female perch in
      Molnbyggen was confirmed in February 1999. In July 1999, at an early stage of
      oogenesis, perch from Molnbyggen showed significantly decreased gonadosomatic
      index (GSI) and aromatase activity. The presence of aromatase inhibiting
      substances in lake sediments were therefore tested in vitro. The aromatase
      activity was dose-dependently inhibited by clotrimazole, reaching 50% inhibition
      at a concentration of 0.9 microM. Aromatase inhibiting substances were found both
      in Molnbyggen and reference sediment extracts, indicating that they were
      naturally occurring substances and not of anthrophogenic origin. The similar
      decrease in levels of circulating steroids (P, 17alpha-OHP, T, and E2),
      aromatase, and GSI therefore suggest that the low aromatase activity is due to
      down-regulation rather than inhibition. To further investigate the
      steroidogenesis prior to T, P, and 17alpha-OHP were analysed in perch caught in
      1997 and 1998 in Lakes Molnbyggen, Kvarntjarn (downstream), Yxen (upstream), and
      Djursjon, in female roach caught in Molnbyggen and Djursjon in 1997, and in brook
      trout caught in Vadbacken and the reference stream Bjorntjarnsbacken in 1998. The
      absence of differences in P and 17alpha-OHP levels, combined with a significantly
      lower T level in female perch and roach from Molnbyggen in 1997, could be the
      result of either increased metabolism and excretion of T, or a disruption
      downstream of 17alpha-OHP formation. The unaffected P levels and significantly
      lower 17alpha-OHP levels, together with significantly decreased T and E2 levels,
      found in adult (>45g) female brook trout from Vadbacken, further indicated that
      an altered steroidogenesis downstream of P is one possible mechanism underlying
      the low T levels and thus the high number of SIM female fish, since too low T
      levels might be insufficient to activate the brain-pituitary-gonadal axis.

PMID- 14636635
TI  - Cysteamine-a somatostatin-inhibiting agent-induced growth hormone secretion and
      growth acceleration in juvenile grass carp (Ctenopharyngodon idellus).
AB  - Effects of cysteamine hydrochloride (CSH)-a somatostatin-inhibiting agent on
      growth hormone (GH) secretion from pituitary fragments (PF) or hypothalamus plus
      pituitary fragments (HPF) under static incubation conditions, serum GH, 3,5,3(')
      triiodothyronine (T(3)) and thyroxine (T(4)) levels, and growth in juvenile grass
      carp (Ctenopharyngodon idellus) were investigated. CSH (0.1, 1, and 10 mM) had no
      influences on GH release from PF after 1 and 6h incubation, but was effective in
      stimulating GH release from HPF in a dose-dependent manner after 1 and 6h
      incubation. Moreover, prolonged treatment of HPF with CSH decreased the magnitude
      of enhancement of GH levels in culture medium. CSH and neuropeptides [e.g., human
      GH-releasing hormone (hGHRH, 100 nM), luteinizing hormone-releasing hormone
      analog (LHRH-A, [D-Trp(6),Pro(9)]LHRH, 100 nM)], or salmon gonadotropin-releasing
      hormone analogue (sGnRH-A, [D-Ala(6),Pro(9)]LHRH, 100 nM), alone and in
      combination during static incubation stimulated GH release from HPF after 1h
      incubation; in addition, there was an additive, not a synergistic effect of CSH
      and neuropeptides on stimulation of GH release. Administration of CSH (2.5mg/g
      diet) in combination with LHRH-A (5 microg/g diet) in diet twice daily for 8
      weeks resulted in higher serum GH, T(3), and T(4) levels, ratio of RNA/DNA in
      muscle, food conversion efficiency, and growth rate than CSH or LHRH-A alone. At
      trial termination, significant decreases in condition factors and body lipid
      levels were observed in fish fed with CSH and/or LHRH-A. No significant
      differences were recorded for viscero-somatic index, hepato-somatic index, and
      percent body moisture and protein in muscle. These findings, taken as a whole,
      strongly suggest that the action of CSH stimulating GH release in vitro appears
      to be mediated through hypothalamic pathways and dietary delivery of CSH directly
      or indirectly stimulates endogenous GH, T(3), and T(4) secretion, and
      subsequently leads to a increase in growth rate in grass carp.

PMID- 14636636
TI  - Daily variation in the concentration of melatonin and 5-methoxytryptophol in the
      goose pineal gland, retina, and plasma.
AB  - The goose pineal gland rhythmically produces two 5-methoxyindole compounds,
      namely melatonin and 5-methoxytryptophol. Melatonin concentrations were high at
      night and low during the day, while in contrast 5-methoxytryptophol levels were
      markedly higher during the day compared to the night-time values. Rhythmic
      oscillations in melatonin content, with high night-time values, have also been
      found in plasma and the retina of goose. The pineal and retinal melatonin rhythm
      mirrored oscillations in the activity of serotonin N-acetyltransferase (AA-NAT;
      the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway).
      Acute exposure of geese to light at night markedly decreased melatonin levels in
      the pineal, plasma, and retina. In addition, this light exposure resulted in a
      significant increase in pineal 5-methoxytryptophol content. Our results
      demonstrate, for the first time, the ability of the goose pineal gland and retina
      to synthesise melatonin and 5-methoxytryptophol in a rhythmic manner.

PMID- 14636637
TI  - Effects of orchidectomy and testosterone replacement on mouse enkephalin
      degrading aminopeptidase activity in the HPA axis.
AB  - Opiates are involved in the regulation of several functions in the hypothalamus
      pituitary-adrenal (HPA) axis under physiological conditions. The aim of the
      present work is to study the influence of orchidectomy and testosterone (T)
      replacement on soluble (S) and membrane bound (MB) enkephalin-degrading
      aminopeptidase (EDA) activities in the HPA axis. Forty male mice (Balb/C) were
      distributed in five groups: sham-operated control (C), orchidectomized (OR-C),
      and orchidectomized treated with increasing doses of T (3, 6 or 12 mg/kg). In
      hypothalamus, orchidectomy did not modify either S or MB EDA, although T
      replacement increased S but not MB EDA. In pituitary, neither S nor MB EDA
      activities changed with orchidectomy, although both activities changed after T
      replacement. On the other hand, in adrenal glands, orchidectomy increased S and
      MB EDA activities, whereas T replacement returned both activities to control
      levels. These results suggest a direct effect of T in S and MB EDA activities and
      therefore, an influence on their endogenous substrates regulation.

PMID- 14636638
TI  - Gonadotropin regulation of follistatin expression in the cultured ovarian
      follicle cells of zebrafish, Danio rerio.
AB  - Follistatin is a single-chain glycoprotein initially identified in the mammalian
      ovary. As a specific binding protein of activin, it effectively modifies the
      paracrine/autocrine roles of activin in a variety of tissues including the ovary.
      In the zebrafish, we have demonstrated that the human chorionic gonadotropin
      (hCG)-induced oocyte maturation and oocyte maturational competence can be blocked
      by follistatin, suggesting a role for ovarian activin in the signaling pathway of
      gonadotropin in the zebrafish ovary. The up-regulation of zebrafish ovarian
      activin betaA subunit by gonadotropin further supports this hypothesis. Since
      follistatin has extremely high affinity for activin, its expression level in
      various tissues is critical in fine-tuning local activin activities. In the
      present study, we investigated the regulation of follistatin expression by
      gonadotropin in a primary culture of zebrafish ovarian follicle cells using semi
      quantitative RT-PCR. Both hCG and goldfish pituitary extract strongly increased
      the expression of follistatin in the cultured follicle cells in clear time- and
      dose-dependant manners. The effect of hCG (15IU/ml) reached the maximal level at
      2h of treatment and longer treatment (4-8h) led to decreased response. The up
      regulation of follistatin expression by hCG could be mimicked by all the drugs
      that increase the intracellular cAMP level including 8-Br-cAMP, db-cAMP,
      forskolin, and 3-isobutyl-1-methylxanthine (IBMX). The hCG (15IU/ml)- and
      forskolin (10microM)-induced follistatin expression could be blocked by H89
      (10microM), a specific protein kinase A (PKA) inhibitor. These results strongly
      suggest that the regulation of follistatin expression in the zebrafish ovary by
      gonadotropin is primarily mediated by cAMP-PKA signaling pathway. The up
      regulation of follistatin mRNA by gonadotropin in cultured zebrafish ovarian
      follicle cells, together with our previous studies on gonadotropin regulation of
      activin beta subunits, suggests that the ovarian activin-follistatin system is
      tightly controlled by gonadotropin in fish ovary.

PMID- 14636639
TI  - Protecting embryos from stress: corticosterone effects and the corticosterone
      response to capture and confinement during pregnancy in a live-bearing lizard
      (Hoplodactylus maculatus).
AB  - Hormones in the embryonic environment, including those of the hypothalamo
      pituitary-adrenal (HPA) axis, have profound effects on development in eutherian
      mammals. However, little is known about their effects in reptiles that have
      independently evolved viviparity. We investigated whether exogenous
      corticosterone affected embryonic development in the viviparous gecko
      Hoplodactylus maculatus, and whether pregnant geckos have a corticosterone
      response to capture and confinement that is suppressed relative to that in non
      pregnant (vitellogenic) females and males. Corticosterone implants (5 mg, slow
      release) administered to females in mid-pregnancy caused a large elevation of
      corticosterone in maternal plasma (P<0.001), probable reductions in embryonic
      growth and development (P=0.069-0.073), developmental abnormalities and eventual
      abortions. Cool temperature produced similar reductions in embryonic growth and
      development (P< or =0.036 cf. warm controls), but pregnancies were eventually
      successful. Despite the potentially harmful effects of elevated plasma
      corticosterone, pregnant females did not suppress their corticosterone response
      to capture and confinement relative to vitellogenic females, and both groups of
      females had higher responses than males. Future research should address whether
      lower maternal doses of corticosterone produce non-lethal effects on development
      that could contribute to phenotypic plasticity. Corticosterone implants also led
      to increased basking in pregnant females (P<0.001), and basal corticosterone in
      wild geckos (independent of reproductive condition) was positively correlated
      with body temperature (P<0.001). Interactions between temperature and
      corticosterone may have broad significance to other terrestrial ectotherms, and
      body temperature should be considered as a variable influencing plasma
      corticosterone concentrations in all future studies on reptiles.

PMID- 14636640
TI  - Effects of steroid hormones on spermatogenesis and GnRH release in male Leopard
      frogs, Rana pipiens.
AB  - Several lines of evidence suggest reproduction in the ranid frogs is potently
      regulated by the gonadal steroids, in particular 5alpha-dihydrotestosterone (DHT)
      and 17beta-estradiol (E(2)), and a non-gonadal steroid, the stress hormone
      corticosterone (Cort). Little is known about how these steroid hormones act upon
      the GnRH system to regulate the downstream reproductive events. We address these
      gaps in our knowledge by investigating the effects of Cort, E(2), and DHT
      administration on the in vitro release of GnRH and on the spermatogenesis of
      adult male leopard frog, Rana pipiens. R. pipiens were implanted for 20 days with
      silastic capsules containing cholesterol (Ch; control), Cort, E(2), or DHT. Upon
      sacrifice, acute hypothalamic explants were cultured and measured for GnRH
      release, and testes processed for histological analysis. Although only E(2)
      implant significantly reduced the gonadosomatic index, all three steroid hormones
      altered spermatogenesis. Cort modestly but significantly reduced the presence of
      spermatids. The effects of E(2) and DHT were both stimulatory and inhibitory,
      depending on the stage of spermatogenesis. None of the steroid hormones altered
      baseline GnRH release. Interestingly, only E(2) significantly stimulated
      veratridine-induced GnRH release, suggesting E(2) treatment increased the
      releasable pool of GnRH and/or enhance the excitability of GnRH neurons. In sum,
      this is the first study to report the direct measurement of GnRH secretion in a
      poikilothermic tetrapod. Our results revealed potent but sometimes paradoxical
      effects of steroid hormones, especially E(2), on the reproductive regulation of
      the male R. pipiens.

PMID- 14636641
TI  - Characterizing a proopiomelanocortin cDNA cloned from the brain of the Bichir,
      Polypterus senegalus: evaluating phylogenetic relationships among ray-finned
      fish.
AB  - There is general agreement that the polypteriform fishes, like Polypterus
      senegalus, constitute a unique lineage in the evolution of the vertebrates.
      However, the precise position of these fishes had been a point of controversy
      since the time of Darwin and Huxley. There is now consensus that the
      polypteriform fishes are members of superorder Actinopterygii. However, within
      the Actinopterygii, it is still debatable as to whether the polypteriform fishes
      are an early offshoot of the Actinopterygii or a more recent sister group to the
      sturgeon and other extant chondrostean fishes. In this study the sequence of
      proopiomelanocortin (POMC), the common precursor for the melanocortins and beta
      endorphin, was used to evaluate the phylogenetic position of the polypteriform
      fishes relative to other bony fishes. 3(')RACE and 5(')RACE protocols were used
      to amplify overlapping regions of a POMC cDNA from the brain of P. senegalus. The
      full-length POMC cDNA had an open reading frame that encoded 259 amino acids. As
      seen in most gnathostomes, P. senegalus POMC has three melanocortin sequences
      (ACTH/alpha-MSH, gamma-MSH, and beta-MSH), and a beta-endorphin region. For
      phylogenetic analysis, the following POMC sequences were aligned at the amino
      acid level and analyzed using a maximum parsimony algorithm: P. senegalus,
      dogfish, sturgeon A, paddlefish A, sockeye salmon A, tilapia, and gar. The
      dogfish POMC sequence was used as the out-group. In this analysis the P.
      senegalus POMC sequence formed a clade with the chondrostean POMC sequences
      (sturgeon A and paddlefish A), and not with the neopterygian sequences (sockeye
      salmon A, tilapia, and gar). P. senegalus POMC is remarkably similar to sturgeon
      POMC A. In particular, in both precursors there is evidence for degeneration at
      the proteolytic cleavage site that precedes the gamma-MSH sequence. Based on the
      analysis of this nuclear gene it would appear that P. senegalus belongs to a
      branch of the chrondrostean lineage rather than representing a lineage of ray
      finned fish that is ancestral to the chondrostean and neoptyergian ray-finned
      fishes. Alternatively, if the polypteriform fishes are in fact an early offshoot
      of the Actinopterygii (the traditional view), then the observations made for P.
      senegalus POMC relative to the chondrostean POMC sequences is the result of
      convergence.

PMID- 14636642
TI  - Iron overload in Africans and African-Americans and a common mutation in the
      SCL40A1 (ferroportin 1) gene.
AB  - The product of the SLC40A1 gene, ferroportin 1, is a main iron export protein.
      Pathogenic mutations in ferroportin 1 lead to an autosomal dominant hereditary
      iron overload syndrome characterized by high serum ferritin concentration, normal
      transferrin saturation, iron accumulation predominantly in macrophages, and
      marginal anemia. Iron overload occurs in both the African and the African
      American populations, but a possible genetic basis has not been established. We
      analyzed the ferroportin 1 gene in 19 unrelated patients from southern Africa (N
      = 15) and the United States (N = 4) presenting with primary iron overload. We
      found a new c. 744 C-->T (Q248H) mutation in the SLC40A1 gene in 4 of these
      patients (3 Africans and 1 African-American). Among 22 first degree family
      members, 10 of whom were Q248H heterozygotes, the mutation was associated with a
      trend to higher serum ferritin to amino aspartate transferase ratios (means of
      14.8 versus 4.3 microg/U; P = 0.1) and lower hemoglobin concentrations (means of
      11.8 versus 13.2 g/dL; P = 0.1). The ratio corrects serum ferritin concentration
      for alcohol-induced hepatocellular damage. We also found heterozygosity for the
      Q248H mutation in 7 of 51 (14%) southern African community control participants
      selected because they had a serum ferritin concentration below 400 microg/L and
      in 5 of 100 (5%) anonymous African-Americans, but we did not find the change in
      300 Caucasians with normal iron status and 25 Caucasians with non-HFE iron
      overload. The hemoglobin concentration was significantly lower in the African
      community controls with the Q248H mutation than in those without it. We conclude
      that the Q248H mutation is a common polymorphism in the ferroportin 1 gene in
      African populations that may be associated with mild anemia and a tendency to
      iron loading.

PMID- 14636643
TI  - Ferroportin 1 (SCL40A1) variant associated with iron overload in African
      Americans.
AB  - We find that in the Black American population average ferritin levels are higher
      than those in Whites, both among men and women. African-Americans have an
      increased prevalence of iron storage disease characterized by prominent iron
      deposition in macrophages of the liver and other organs. The iron distribution in
      patients with mutations of the ferroportin gene is similar. A c.744 G-->T (Gln
      248 His) mutation was detected among African-Americans at polymorphic
      frequencies. This variant is associated with increased ferritin levels in African
      Americans and may play a role in their propensity to develop iron overload.

PMID- 14636644
TI  - Genotypic and phenotypic heterogeneity of African Americans with primary iron
      overload.
AB  - Primary iron overload may be relatively common in African Americans, but its
      cause is incompletely understood. Thus, we evaluated genotype and phenotype
      characteristics of unselected African American index patients with primary iron
      overload who reside in central Alabama. All had hepatic iron concentration > or
      =30 micromol/g dry wt or > or =2.0 g of iron mobilized by phlebotomy to achieve
      iron depletion. Genotype analyses were performed in African American control
      subjects from the same region. There were 23 patients (19 men, 4 women); mean age
      at diagnosis was 52 +/- 12 years (1 SD) (range 32-69 years). Nine (39.1%)
      reported that they consumed > or =45 g of ethanol daily; five had chronic
      hepatitis C. Eight had some form of hemoglobinopathy or thalassemia. Mean serum
      transferrin saturation was 56 +/- 28% (range 15-100%). The geometric mean serum
      ferritin at diagnosis was 1076 ng/mL [95% confidence interval 297-3473 ng/mL].
      Increased stainable liver iron was observed in hepatocytes only in 4 patients, in
      macrophages only in 8 patients, and in hepatocytes and macrophages in 8 patients.
      The mean quantity of iron mobilized by phlebotomy (corrected for iron absorbed
      during treatment) was 5.3 +/- 2.0 g (range 4.0-8.4 g). Iron removed by phlebotomy
      was greater in patients with hemoglobinopathy or thalassemia than in those
      without these forms of anemia (6.6 +/- 1.3 g vs 3.9 +/- 1.6 g, respectively; P =
      0.0144). Daily consumption of > or =45 g of ethanol or chronic hepatitis C was
      not associated with an increased or decreased amount of phlebotomy-mobilized
      iron, on the average. The percentage of index patients positive for HFE C282Y was
      greater than that of controls (P = 0.0058). The respective percentages of
      phenotype positivity for HFE H63D, D6S105(8), and HLA-A*03 were similar in
      patients and controls. HFE S65C, I105T, and G93R were not detected in index or
      control subjects. Two of 13 patients were heterozygous for the ferroportin allele
      nt 744 G-->T (Q248H), although the phenotype frequency of this allele was similar
      in patients and 39 controls. Synonymous ferroportin alleles were also detected in
      some patients. The ceruloplasmin mutation nt 1099C-->T (exon 6; Arg367Cys) was
      detected in 1 of 2 patients tested. Abnormal alleles of beta-2 microglobulin,
      Nramp2, TFR2, hepcidin, or IRP2 alleles were not detected in either of the 2
      patients so tested. We conclude that primary iron overload in African Americans
      is not the result of the mutation of a single gene. HFE C282Y, ferroportin 744 G-
      >T, and common forms of heritable anemia appear to account for increased iron
      absorption or retention in some patients.

PMID- 14636645
TI  - Familial Mediterranean fever with amyloidosis associated with novel exon 2
      mutation (S1791) of the MEFV gene.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterized by recurrent attacks of fever, serositis, and a risk for AA
      amyloidosis. FMF is caused by mutations in the Mediterranean fever gene (MEFV),
      which is expressed in blood cells of the myelomonocytic differentiation pathway.
      We identified a novel mutation S1791 in exon 2 of MEFV in two members of a family
      of Turkish origin. In both cases, S1791 was in compound heterozygosity with MEFV
      mutation M694V, and the characteristic clinical syndrome of FMF including
      amyloidosis was found. The location of S1791 in exon 2 is of interest because (1)
      amyloidosis in FMF has previously been found to be strongly associated with
      compound exon 10 mutations and (2) it supports the notion that the mechanism
      causing FMF is connected to the cytoplasmic rather than nuclear function of the
      molecule.

PMID- 14636646
TI  - Blood group does not correlate with disease severity in patients with Fabry
      disease (alpha-galactosidase A deficiency).
AB  - Blood groups B and P1 are substrates for the lysosomal enzyme alpha-galactosidase
      A. Therefore, patients with alpha-Gal A deficiency and blood groups B or P1 may
      exhibit more severe disease. In 48 Fabry patients distribution of blood group was
      not different from that in the Dutch population. No patient had blood group B.
      Clinical symptoms did not differ between bloodgroup P1 or P2 patients. We
      conclude that blood groups B and P1 are not overrepresented in Dutch Fabry
      patients. Blood group P1 is not correlated with more severe disease and cannot be
      considered a significant risk factor.

PMID- 14636647
TI  - Possible primary familial and congenital polycythemia locus at 7q22.1-7q22.2.
AB  - Primary familial and congenital polycythemia (PFCP), inherited as an autosomal
      dominant trait, has been reported to be associated with mutations in the gene
      encoding the erythropoietin receptor (EpoR). The clinical features include the
      presence of isolated erythrocytosis, low erythropoietin (Epo) levels, normal
      hemoglobin-oxygen dissociation curve, hypersensitivity of erythroid progenitors
      to exogenous Epo in vitro and no progression to leukemia or myelodysplastic
      syndrome. Less than 15% of PFCP families have an identifiable EPOR mutation.
      Abnormalities of other genes are therefore likely responsible for the phenotype
      of the majority PFCP patients. In this study we report a family segregating PFCP
      with an autosomal dominant pattern of inheritance, where 7 of 14 members of the
      family were affected in four generations. This family was studied previously and
      an EPOR mutation was ruled out by sequencing and by genetic means. Here, we
      confirmed by linkage analysis that the disease phenotype was not linked to the
      Epo and EPOR genes. We then performed a genomewide screen with 410 polymorphic
      markers at average spacing 7.67 cM to locate the chromosomal region responsible
      for PFCP. We identified a region in 7q22.1-7q22.2 with a suggestive LOD score of
      1.84, from our data this is the most likely location of a candidate region
      responsible for PFCP in this family.

PMID- 14636648
TI  - Wiskott-Aldrich syndrome in a female with skewed X-chromosome inactivation.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by
      immunodeficiency, eczema, and thrombocytopenia with small platelets. The
      phenotype of affected males is usually severe, although female carriers of the
      disorder have no clinical signs of the genetic defect. This is explained by the
      preferential selection of the normal, nonmutated X-chromosome, as the active
      allele in hematopoietic cells. In the present article we describe a female case
      of WAS, with a G-to-A transition in the WASP gene at nucleotide 291. She displays
      mild thrombocytopenia, with both normal and small-sized platelets. A methylation
      analysis of the HUMARA gene showed a nonrandom X-chromosome inactivation pattern
      in which the X-chromosome carrying the normal WASP gene was preferentially
      inactivated, leaving the mutant gene active. Thus, our results suggest that
      skewed X-inactivation, favoring the WASP-mutated allele, is the mechanism
      underlying the WAS phenotype of this girl. Moreover the results alert us to the
      fact that particular females, with a family history of WAS, may develop certain
      signs of the disease.

PMID- 14636649
TI  - Regulation of granulocyte and monocyte differentiation by CCAAT/enhancer binding
      protein alpha.
AB  - CCAAT/enhancer binding protein alpha (C/EBPalpha)-ER induces 32Dcl3 neutrophilic
      differentiation and inhibits 32DPKCdelta maturation to macrophages in response to
      phorbol ester. In 32Dcl3 cells, C/EBPalpha-ER rapidly induces the PU.1 and
      C/EBPalpha RNAs even in the presence of cycloheximide, suggesting that these are
      direct C/EBPalpha genetic targets. C/EBPalpha strongly binds and modestly
      activates the murine PU.1 promoter via an evolutionarily conserved binding site.
      C/EBPalpha-ER variants incapable of binding DNA still slow G1 progression but do
      not induce differentiation. N-terminally truncated C/EBPalpha variants, including
      the p30 isoform expressed in a subset of AMLs, also retain the ability to slow
      32D cl3 proliferation, whereas the C/EBPalpha(BRM2)-ER variant does not slow G1
      progression, has a reduced capacity to induce early granulocytic markers, and
      does not induce terminal maturation. In 32DPKCdelta cells, C/EBPalpha-ER strongly
      inhibits endogenous or exogenous JunB induction, dependent upon the outer surface
      of the C/EBPalpha basic region, but does not inhibit c-Jun, PU.1, or C/EBPbeta
      expression. Exogenous JunB restores AP-1 DNA binding but does not overcome
      inhibition of monopoiesis by C/EBPalpha-ER. In summary, we propose that while
      C/EBPalpha is required for development of immature granulocyte-monocyte
      progenitors, C/EBPalpha subsequently inhibits monopoiesis, via inhibition of JunB
      express and via additional activities, and induces granulopoiesis, via induction
      of PU.1, C/EBPepsilon, and cell cycle arrest.

PMID- 14636650
TI  - The emerging role of the myeloid Elf-1 like transcription factor in
      hematopoiesis.
AB  - MEF (myeloid Elf-1 like factor) is a member of the ETS family of transcription
      factors (TF) with transcriptional activating properties. ETS proteins have been
      implicated in widely divergent physiological and pathological processes (such as
      development and oncogenesis). MEF is expressed in non-hematopoietic and
      hematopoietic (lymphoid and myeloid) tissues, and after generating MEF-deficient
      mice by homologous recombination, we have studied its role in lymphopoiesis
      (Immunity 17 (2002), 437). MEF plays a critical role in NK and NK-T cell
      development and the constitutive expression of perforin by NK cells. MEF
      interacts with other TFs such as AML1 (Runx1) and with the cyclin A/cdk2 kinase
      complex. In this review, we discuss the biology of MEF in the context of the
      other members of this family of transcriptional regulators.

PMID- 14636651
TI  - Mutations in GATA1 in both transient myeloproliferative disorder and acute
      megakaryoblastic leukemia of Down syndrome.
AB  - Mutations in transcription factors often contribute to human leukemias by
      providing a block to normal differentiation. To determine whether mutations in
      the hematopoietic transcription factor GATA1 are associated with leukemia, we
      assayed for alterations in the GATA1 gene in bone marrow samples from patients
      with various subtypes of acute leukemia. Here we summarize our findings that
      GATA1 is mutated in the leukemic blasts of patients with Down syndrome acute
      megakaryoblastic leukemia (DS-AMKL). We did not find mutations in GATA1 in
      leukemic cells of DS patients with other types of acute leukemia, or in other
      patients with AMKL who did not have DS. Furthermore, we did not detect GATA1
      mutations in DNAs from over 75 other patients with acute leukemia or from 21
      healthy individuals. Since the GATA1 mutations were restricted to DS-AMKL, we
      also investigated whether GATA1 was altered in the "preleukemia" of DS, transient
      myeloproliferative disorder (TMD). TMD is a common myeloid disorder that affects
      10% of DS newborns and evolves to AMKL in nearly 30% patients. We detected GATA1
      mutations in TMD blasts from every infant examined. Together, these results
      demonstrate that GATA1 is likely to play a critical role in the etiology of TMD
      and DS-AMKL, and that mutagenesis of GATA1 represents a very early event in DS
      myeloid leukemogenesis. We hypothesize that disruption of normal GATA-1 function
      is an essential step in the initiation of megakaryoblastic leukemia in DS.

PMID- 14636652
TI  - Red cell membrane protein deficiencies in Mexican patients with hereditary
      spherocytosis.
AB  - Twenty-seven families and four individual patients with hereditary spherocytosis
      (HS) from the northwestern region of Mexico were studied. An autosomal dominant
      inheritance pattern was identified in 59% of 22 families. Densitometric analysis
      of erythrocyte membrane proteins revealed individual protein deficiencies in 39%
      of the patients studied, in whom the principal altered proteins were the alpha
      spectrins (13%), band 3 protein (10%), ankyrin (6%), 4.2 protein (6%), and the
      beta spectrins (3%). A predominant deficiency of spectrins has also been observed
      in other Latin American and Mediterranean countries. However, it is well known
      that deficiencies in these proteins are heterogeneous across different ethnic
      groups. A combined protein deficiency was observed in 52% of patients, most
      frequently involving the spectrins, band 3 protein, 4.2 protein, and 4.1 protein.
      In three subjects, no abnormalities were detected (10%). We conclude that,
      despite the observed heterogeneity, the principal affected proteins are
      essentially similar to those observed in other ethnic groups.

PMID- 14636653
TI  - Effects of human locus control region elements HS2 and HS3 on human beta-globin
      gene expression in transgenic mouse.
AB  - The locus control region (LCR) is the most important cis-element in the
      regulation of beta-globin gene expression. DNaseI-hypersensitive site (HS) 2 and
      HS3 are two significant components of beta-LCR. To examine the effect of HS2,
      HS3, and HS2-HS3 (combination of HS2 and HS3) on the spatial and temporal
      expression of the human beta-globin gene, we have produced transgenic mice with
      constructs, in which the gene encoding enhanced green fluorescent protein (EGFP)
      is driven by beta-globin promoter and under the control of HS2, HS3, and HS2-HS3,
      respectively. The results showed that HS2 and HS3 each had the same enhancement
      activity in regulation of beta-globin gene expression in transgenic mice. When
      HS2 and HS3 were in combination (HS2-HS3), the two cis-elements showed a marked
      synergy in regulating beta-globin gene spatial and temporal expression as well as
      its expression level in transgenic mice although the EGFP expression varied
      largely among different transgenic mouse litters. The results also showed that
      HS2 was able to confer beta-globin gene expression in embryonic yolk sac, fetal
      liver, and adult bone marrow, which was not developmentally stage-specific, while
      HS3 could confer the same beta-globin gene expression in the adult. Thus, HS3 was
      different from HS2, the former being more important for specific expression of
      beta-globin gene in the developmental stages and the switch of gamma-->beta
      globin genes. Our results indicate that the mechanism of gamma-->beta switch
      could be best explained by the "divided model."

PMID- 14636656
TI  - Evaluating the impact of passengers on the safety of older drivers.
AB  - PROBLEM: This study involved a quasi-induced exposure analysis of 4 years of
      crashes involving older drivers in the state of Kentucky. METHOD: Single- and
      multivehicle crashes were disaggregated according to the number of passengers:
      (a) no passenger, (b) one passenger, and (c) two or more passengers. RESULTS:
      Overall, the presence of two or more passengers was found to negatively impact
      the probability that drivers 75 years of age or older were at fault in crashes.
      Several potential factors were studied for interactive effects with passengers:
      vehicle occupant gender mix, time of the day, road curvature, grade, and number
      of lanes. The negative impact of passengers increased for some geometric road
      conditions. However, older drivers were found to be safer at night when carrying
      two or more passengers. The presence or absence of passengers was not found to
      affect the 65- to 74-year-old driver group. Groups of male vehicle occupants with
      a 75+ male driver were found to have high single-vehicle crash rates. IMPACT:
      These results are among the first to directly consider the effect of passengers
      on the crash-causing propensity of older drivers and the findings suggest more
      work is warranted to consider causes for the crash rate differences.

PMID- 14636654
TI  - Differential gene expression in the kidney of sickle cell transgenic mice:
      upregulated genes.
AB  - The S+S-Antilles transgenic mouse used in this study has renal defects similar to
      those seen in sickle cell anemia patients: congested glomeruli, medullary
      fibrosis, renal enlargement, vasoocclusion, and a urine concentrating defect. We
      used gene expression microarrays to identify genes highly up-regulated in the
      kidneys of these mice and validated their expression by real-time PCR. Kidney
      hypoxia, as demonstrated by the presence of deoxyhemoglobin, was detected by
      blood oxygen dependent magnetic resonance imaging (BOLD-MRI). Some of the up
      regulated genes included cytochrome P450 4a14, glutathione-S-transferase alpha-1,
      mitochondrial hydroxymethylglutaryl CoA synthase, cytokine inducible SH-2
      containing protein, retinol dehydrogenase type III, arginase II, glycolate
      oxidase, Na/K ATPase, renin-1, and alkaline phosphatase 2. An increase in enzyme
      activity was also demonstrated for one of the up-regulated genes (arginase II).
      These genes can be integrated into several different pathophysiological
      processes: a hypoxia cascade, a replacement cascade, or an ameliorating cascade,
      one or all of which may explain the phenotype of this disease. We conclude that
      microarray technology is a powerful tool to identify genes involved in renal
      disease in sickle cell anemia and that the identification of various metabolic
      pathways may open new avenues for therapeutic interventions.

PMID- 14636657
TI  - Impact of impulsiveness, venturesomeness, and empathy on driving by older adults.
AB  - PROBLEM: Although personality characteristics such as impulsiveness have been
      linked to the driving safety and driving habits of young and middle-aged adults,
      little research has focused on the role of personality in older driver behavior.
      METHOD: Using the IVE questionnaire in an exploratory study, three personality
      dimensions (impulsiveness, venturesomeness, and empathy) were measured in 305
      older drivers (ages 57-87 years old). In addition, the Driving Habits
      Questionnaire was used to estimate driving exposure, and the Driver Behavior
      Questionnaire (DBQ) was used to estimate driving errors and violations. State
      recorded crash data were made available by the state public safety agency.
      RESULTS: Subjects who reported four or more driving errors had higher impulsivity
      and empathy scores and lower venturesomeness scores. Subjects reporting driving
      violations were more likely to have high impulsivity scores. Driving six or more
      places per week was associated with lower levels of impulsivity. IMPACT: These
      results suggest that a comprehensive understanding of driving problems among
      older adults should also include a consideration of personality dimensions. In
      doing so, the challenges faced in the interpretation of self-report instruments
      on driving behaviors must be acknowledged, with a move in research toward greater
      reliance on more objective measures of driving behavior when assessing the impact
      of personality variables.

PMID- 14636659
TI  - Improving older driver knowledge and self-awareness through self-assessment: the
      driving decisions workbook.
AB  - PURPOSE: This study aims to assess whether the Driving Decisions Workbook, a self
      assessment instrument for older drivers, increased self-awareness and general
      knowledge. This study also assessed perceptions regarding its usefulness,
      particularly as a tool for facilitating discussions within families of older
      drivers. A secondary purpose of the study was to determine if problems identified
      by drivers in the workbook related to problems they had with actual driving.
      DESIGN AND METHODS: The Driving Decisions Workbook was administered along with a
      questionnaire and a road test. A convenience sample of 99 licensed drivers aged
      65 and above was used. RESULTS: After completing the workbook, about three
      fourths of the participants reported being more aware of changes that could
      affect driving. Fourteen percent reported that they had discovered a change in
      themselves of which they had not been previously aware. All respondents found the
      workbook to be at least a little useful and thought the workbook could help
      facilitate family discussions. Workbook responses were positively correlated with
      overall road test scores. Significant correlations were also noted between the
      road test and a majority of workbook subsection responses. IMPLICATIONS: This
      study indicates that the workbook may be a useful first-tier assessment
      instrument and educational tool for the older driver. It may encourage an older
      driver to drive more safely and/or to seek clinical assessment, and help in
      facilitating discussions about driving within their families.

PMID- 14636658
TI  - Driving disability and dizziness.
AB  - PROBLEM: People with dizziness caused by vestibular (i.e., inner ear) disorders
      complain of difficulty driving. Physicians occasionally warn their patients with
      vestibular disorders not to drive. Few studies have asked patients about their
      driving performance, so little data are available. METHOD: Using the Driving
      Habits Questionnaire, the authors did structured interviews with people with
      several different vestibular disorders and with normal subjects. The self
      reported crash rate and rate of citations for moving violations did not differ
      between the subject groups. RESULTS: Patients report reduced driving skills,
      particularly in situations when visual information is reduced, rapid head
      movements are used, and specific path integration or spatial navigation skills
      are needed.

PMID- 14636660
TI  - Deconstructing a gender difference: driving cessation and personal driving
      history of older women.
AB  - PROBLEM: The purpose of this study is to understand the reasons behind older
      women's driving cessation by comparing the driving histories of Finnish women who
      either gave up or renewed their drivers license at the age of 70. METHOD: A mail
      survey was sent to all Finnish women born in 1927 who gave up their license in
      1997 (N=1,476) and to a corresponding random sample of women who renewed their
      license (N=1,494). The total response rate was 42.1%. RESULTS: The length and
      level of activity of personal driving history were strongly associated with
      driving cessation and continuation. Ex-drivers tended to have an inactive driving
      career behind them, whereas drivers had a more active personal driving history.
      In addition, those women with an active, "male-like" driving history who had
      decided to stop driving gave reasons for driving cessation that were similar to
      what is known about older men's reasons to give up driving. The results suggest
      that the decision to stop driving is related to driving habits rather than
      gender.

PMID- 14636661
TI  - MaryPODS revisited: updated crash analysis and implications for screening program
      implementation.
AB  - PROBLEM: Due to the relative scarcity of crashes, there has consistently been a
      problem with analyses that use crashes as a criterion measure in their analyses.
      METHOD: Previous analyses of the relationships between functional capacity
      measures and at-fault crash involvement for older drivers as reported in the
      NHTSA Model Driver Screening and Evaluation Program Final Technical Report have
      been updated to include one additional year of driving experience. Eighteen new
      at-fault crashes involving drivers who previously had no crash involvement were
      recorded for the Maryland Motor Vehicle Administration (MVA) test sample during
      this interval. The method of odds ratio (OR) calculation was used to examine the
      relationships between functional status predictors and the most salient among the
      safety outcome measures identified in the Maryland research. Peak valid OR values
      for the prior and current analyses were contrasted, and the stability of
      candidate pass-fail cut-points for each predictor relative to values identified
      in the Final Technical Report was examined. RESULTS: Results indicate that the
      predictive value of functional tests appears to decrease over time, particularly
      for the perceptual-cognitive measures. IMPACT ON INDUSTRY: The impact of these
      findings on programs and policies is to underscore a need for periodic
      reevaluation, spaced at the shortest practical intervals but not more than 2
      years apart, in order for functional capacity screening to be applied effectively
      by licensing authorities, health care professionals, and others to reduce
      personal risk and enhance public safety.

PMID- 14636662
TI  - Older women drivers: fatal crashes in good conditions.
AB  - PROBLEM: By 2030, there will be approximately 70 million older people (65+) in
      the United States, more than twice their number in 2000. This increase also
      represents an increased percentage of older licensed drivers. Thus, it is
      important to understand the special circumstances of how they may be involved in
      traffic crashes. METHOD: This study used the Fatality Analysis Reporting System
      (FARS), which is a census of all fatal crashes occurring in the United States
      over the last two decades maintained by the National Highway Traffic Safety
      Administration (NHTSA), to study the special characteristics of fatal crashes
      involving females older than 70 years. RESULTS: The results indicate that senior
      women are overrepresented in crashes that occur under the "safest" conditions, on
      roads with low speed limits, in daylight, when traffic is low (not at rush hour),
      when the weather is good, and when the roads are dry.

PMID- 14636663
TI  - Driving and alternatives: older drivers in Michigan.
AB  - METHOD: A statewide telephone survey of Michigan drivers and former drivers aged
      65 and older collected information on transportation mode choices, experience
      with alternatives to driving, and whether drivers planned for when they could no
      longer drive. RESULTS: Results showed that most older adult households owned at
      least one automobile, and that the automobile was the primary mode of
      transportation. Most former drivers obtained rides from relatives and friends.
      Use of public transportation was low, and some seniors were not aware of
      available public transportation services. Older drivers did not plan for driving
      cessation. Over half the drivers who perceived a likelihood of driving problems
      within 5 years expected to keep driving beyond 5 years. IMPACT ON INDUSTRY:
      Because of their lifelong reliance on the automobile, their desire to drive
      themselves, and their lack of experience with public transportation, efforts to
      enhance the mobility of older people should consider this background while
      alternatives to the personal automobile are developed.

PMID- 14636664
TI  - Assessment of older drivers: relationships among on-road errors, medical
      conditions and test outcome.
AB  - PROBLEM: It is essential that driver licensing authorities have a valid and
      reliable system for evaluating older drivers' continuing competency; road tests
      are usually required as part of such a system. This study sought to find
      information about the nature of driving errors made during license review tests,
      and about relationships between error type and test outcome for older drivers.
      METHOD: Data from licensing authority files from 533 road tests during a 12-month
      period were analyzed; medical and other referral information was included.
      Average driver age was 76 years. Performance scores were generated for
      intersection negotiation, lane changing, low speed manoeuvres, positioning and
      speed control, safety margin, and car control. RESULTS: Logistic regression
      analysis showed that test outcome was well predicted by a subset of driving
      performance scores; adding driver age to the model explained very little
      variance. Age alone was strongly associated with outcome. Relationships between
      referral information and test outcome are also reported. IMPACT: Results
      highlight several factors relevant to the development of more valid and reliable
      road tests for older drivers.

PMID- 14636665
TI  - On-road driving evaluations: a potential tool for helping older adults drive
      safely longer.
AB  - PROBLEM: This paper explores the potential use of on-road driving evaluations as
      a tool for helping older adults extend their safe driving years. METHOD: Three
      separate research activities were carried out. The first was a national telephone
      survey of current and former older drivers. The results of this survey provide
      information relevant to the potential market for on-road driving evaluations. The
      second was a series of focus groups with potential stakeholders in the process:
      driver educators, occupational therapists, and physicians. These groups explored
      the feasibility and requirements of offering on-road driving evaluations to the
      wider public. Supplemental data were also collected from a mail survey of driving
      schools nationwide. RESULTS: Based on the results of these efforts, a number of
      recommendations are presented for expanding the availability of on-road driving
      evaluations, specifically to help older adults make more responsible decisions
      about continuing or stopping driving, and more generally to help them drive
      safely longer.

PMID- 14636666
TI  - Effect of vehicle and crash factors on older occupants.
AB  - PROBLEM: The expected substantial increase in people aged 65 or older is
      important for those concerned about transportation injuries. However, much of the
      previous research concentrates on older drivers and overlooks the fact that
      vehicle and crash factors may provide significant explanations of older occupant
      injury rates. METHOD: Differences across age groups are explored using two
      nationwide travel surveys, crash involvement, fatalities, and injuries from crash
      databases and an ordered probit model of injury severity. RESULTS AND DISCUSSION:
      Two noticeable differences that help explain injury risk are that older people
      are more likely to travel in passenger cars than younger people who frequently
      use light trucks, and that seriously injured older occupants are more likely to
      be involved in side-impact crashes than their younger counterparts. IMPACT:
      Increased attention to vehicle engagement in side-impact crashes and to vehicle
      technologies that can help drivers avoid side collisions would be particularly
      helpful for older occupants.

PMID- 14636667
TI  - Using a driving simulator to identify older drivers at inflated risk of motor
      vehicle crashes.
AB  - PROBLEM: To develop appropriate assessment criteria to measure the performance of
      older drivers using an interactive PC-based driving simulator, and to determine
      which measures were associated with the occurrence of motor-vehicle crash.
      METHOD: One hundred and twenty-nine older drivers residing in a metropolitan city
      volunteered to participate in this retrospective cohort study. Using the driving
      simulator, appropriate driving tasks were devised to test the older drivers,
      whose performances were assessed by 10 reliable assessment criteria. Logistic
      regression analysis was then undertaken to determine those criteria that
      influence the self-reported crash outcome. RESULTS: As expected, driving skill of
      older drivers was found to decline with age. Over 60% of the sample participants
      reported having at least one motor-vehicle crash during the past year. Adjusting
      for age in a logistic regression analysis, the cognitive abilities associated
      with the crash occurrence were working memory, decision making under pressure of
      time, and confidence in driving at high speed. SUMMARY: The findings of this
      retrospective study indicated those individuals at inflated risk of vehicle
      crashes could be identified using the PC-based interactive driving simulator.
      Prospective studies need to be undertaken to determine whether the driving
      simulator can predict future crash events. IMPACT ON INDUSTRY: This study
      demonstrated an economical driving simulator approach to screen out problematic
      or unsafe older drivers before a more detailed but expensive road test is
      considered.

PMID- 14636668
TI  - The 2001 National Household Travel Survey: a look into the travel patterns of
      older Americans.
AB  - INTRODUCTION: The main objective of this paper is to highlight travel patterns of
      older adults living in the United States as depicted in the 2001 National
      Household Travel Survey (NHTS). The NHTS is a national data collection program
      sponsored by the Bureau of Transportation Statistics and the Federal Highway
      Administration. It is the first national comprehensive household survey of both
      daily and long-distance travel, allowing for analysis of the full continuum of
      personal travel by Americans. To better understand the transportation needs of
      older Americans, it is useful to examine how travel patterns differ across age
      groups. The intent is to present basic travel characteristics of older adults
      (age 65+) and allow for comparisons with younger adults (ages 19-64). Travel
      related characteristics of older adults in the United States: Results of the 2001
      survey showed that older Americans travel extensively and rely on personal
      vehicles as heavily as their younger counterparts. Older Americans conduct 89% of
      their travel in personal vehicles. CHARACTERISTICS OF DAILY TRIPS TAKEN BY OLDER
      ADULTS: Older adults tend to be less mobile in that they take fewer trips, travel
      shorter distances, and have shorter travel times. This pattern is even more
      pronounced among older women. They are also more likely to suffer from self
      reported medical conditions that further limit their travel. Characteristics of
      long-distance travel by older adults: Older men and women take long-distance
      trips at about the same rates and show a strong preference for using personal
      vehicles. And, while men and women take an equal percentage of their trips by
      air, older women show a strong preference for bus travel. CONCLUSIONS: Although
      older Americans travel extensively, they are less mobile than their younger
      counterparts. This pattern is more pronounced among older women and among those
      with self-reported medical conditions that affect their ability to travel outside
      their home. Older women consistently take the least number of trips per day, have
      the lowest driving rates, travel the shortest distances, and are more likely to
      report medical conditions that limit their travel. For men and women who have to
      give up driving, alternative means of transportation becomes a necessity. Yet,
      use of alternative transportation is relatively low; excluding personal vehicle
      and walking, all other means of transportation account for about 2% of daily
      travel. Further, of those with medical conditions that affect their travel, only
      about 12% use special transportation services such as dial-a-ride.

PMID- 14636669
TI  - Recent advances in molecular biology and physiology of the prostaglandin E2
      biosynthetic pathway.
AB  - Prostanoids represent a group of lipid mediators that are produced from
      arachidonic acid via the cyclooxygenase pathway. Once formed, the prostanoids are
      released from the cells and act on their cognate receptors on cell surfaces to
      exert their biological actions. Of these, prostaglandin E(2) (PGE(2)) is the most
      common prostanoid, being produced by a wide variety of cells and tissues and has
      a broad range of bioactivity. Recent advance in this field has led to
      identification and characterization of a number of enzymes that play roles in the
      biosynthesis of PGE(2), namely phospholipase A(2), cyclooxygenase and terminal
      PGE synthase. Each of these three reactions can be rate-limiting and involves
      multiple enzymes/isozymes that can act in different phases of cell activation and
      exhibit distinct functional coupling. In this review, we will overview a recent
      understanding of the molecular biology, regulatory mechanisms, and physiological
      functions of these enzymes.

PMID- 14636670
TI  - Elongation of long-chain fatty acids.

PMID- 14636671
TI  - Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function.
AB  - Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by
      cytochrome P450 epoxygenases, function primarily as autocrine and paracrine
      effectors in the cardiovascular system and kidney. They modulate ion transport
      and gene expression, producing vasorelaxation as well as anti-inflammatory and
      pro-fibrinolytic effects. EETs are incorporated into the sn-2 position of
      phospholipids and are rapidly mobilized when a cell is treated with a Ca(2+)
      ionophore, suggesting that they may play a role in phospholipid-mediated signal
      transduction processes. Soluble epoxide hydrolase (sEH) converts EETs to
      dihydroxyeicosatrienoic acids (DHETs), and inhibition of sEH is a potential
      approach for enhancing the biological activity of EETs. EETs also undergo chain
      elongation and beta-oxidation, and the accumulation of partial beta-oxidation
      products increases when sEH is inhibited. Some functional effects of EETs occur
      through activation of either the guanine nucleotide binding protein Galphas or
      the Src signal transduction pathways, suggesting that EETs act by binding to
      membrane receptors. However, other evidence indicates that the modulation of gene
      expression occurs through an intracellular action of EETs. Because of the
      diversity of biochemical and functional responses produced by EETs, it is
      doubtful that a single mechanism or signal transduction pathway can account for
      all of their actions.

PMID- 14636672
TI  - The ultrastructural architecture of the adult Schistosoma japonicum tegument.
AB  - The tegument of the adult blood fluke Schistosoma japonicum is in direct contact
      with the host blood and immune systems. A comprehensive understanding of the
      ultrastructure of the tegument is crucial to the understanding of how the
      parasite maintains itself within the mammalian host. Important functions such as
      nutritional uptake and immune evasion are suspected functions of the tegument and
      this review discusses these aspects and presents some insights into some of these
      crucial functions. Transmission electron microscopy has allowed the
      identification of ultrastructural features of the adult S. japonicum, some of
      which differ from the reported features of other schistosome species.
      Morphological differences within the tegument of the adult S. japonicum are noted
      between sexes, among different regions of the worms and between aspects along the
      length of the parasite. Differences included variations in the ultrastructure,
      size and number of tegumental bodies and mitochondria within the matrix, and
      differences in the relative area of the apical surface of the tegument. Functions
      of the various components of the tegument matrix and specialised functions of
      different regions of the male and female parasites are discussed based on
      ultrastructural findings and previously reported biochemical and molecular data.

PMID- 14636673
TI  - Identification of mitogen-activated protein kinase homologues from Leishmania
      mexicana.
AB  - Mitogen-activated protein kinases are key-regulatory elements in the
      differentiation, proliferation, apoptosis and stress response of eukaryotic
      cells. Our recent identification of a mitogen-activated protein kinase homologue
      in Leishmania mexicana which is essential for the proliferation of the amastigote
      stage of the parasite living in the parasitophorous vacuole of the infected
      macrophage prompted us to screen the genome of L. mexicana for additional mitogen
      activated protein kinase homologues using degenerate oligonucleotide primers in a
      polymerase chain reaction amplification approach. We cloned and sequenced the
      genes for eight new mitogen-activated protein kinase homologues which were
      subsequently shown to be present in one copy per haploid genome. The mRNA levels
      of the kinases varied significantly in pro- and amastigote life stages of the
      parasite. We used the structural information of the p38 stress-activated protein
      kinase, which belongs to the family of mitogen-activated protein kinases, for the
      alignment of the deduced proteins and the verification of the predicted secondary
      structure elements. All new mitogen-activated protein kinases reveal the typical
      12 subdomain primary structure, the conserved residues characterising
      serine/threonine protein kinases and the characteristic TXY motif in the
      phosphorylation lip. Typical features of some of the molecules are amino acid
      insertions between the subdomains and long carboxy-terminal amino acid extensions
      carrying putative src-homology 3-binding motifs.

PMID- 14636674
TI  - Translocation of ribosomal protein P0 onto the Toxoplasma gondii tachyzoite
      surface.
AB  - A ribosomal phosphoprotein P0 detected on the surface of the human malarial
      parasite Plasmodium falciparum (PfP0) has been shown to be recognised by invasion
      blocking antibodies. Using cross-reactive polyclonal antibodies against PfP0, the
      surface localisation has also been demonstrated on certain mammalian cells, yeast
      and Toxoplasma gondii. We sought to characterise the phenomenon of surface
      localisation in Toxoplasma using T. gondii P0 protein. Sequence analysis of a
      cDNA clone isolated from a T. gondii library showed marked similarity to PfP0,
      suggesting that T. gondii expresses an orthologous gene, TgP0. The expression of
      TgP0 was corroborated by Northern blot analysis revealing a transcript of 1.8 kb
      in size. Immunofluorescence analysis using anti-PfP0 indicated surface
      localisation of TgP0. To confirm surface translocation of the TgP0, tachyzoites
      were transfected with the HA-tagged TgP0 gene followed by immunofluorescence
      detection of the HA-tag. Surface translocation of transiently expressed TgP0 and
      blocking of tachyzoite invasion of human foreskin fibroblasts by anti-PfP0
      antibodies suggest that P0 protein plays an important role in T. gondii invasion
      of human cells.

PMID- 14636675
TI  - Babesia bovis merozoites invade human, ovine, equine, porcine and caprine
      erythrocytes by a sialic acid-dependent mechanism followed by developmental
      arrest after a single round of cell fission.
AB  - Babesia bovis infections have only been observed in bovine species in contrast to
      Babesia divergens that also can infect humans, sheep and rodents. Using an in
      vitro assay that assesses invasion of erythrocytes by free merozoites after a 1-h
      incubation period, it was shown that specificity is not determined by host
      specific interactions associated with invasion. Human erythrocytes were invaded
      more efficiently than bovine erythrocytes whereas erythrocytes of sheep, pigs and
      horses were invaded only slightly less efficiently. In contrast, goat
      erythrocytes were refractory to efficient invasion. Significant differences in
      invasion efficiency into erythrocytes from different individuals of the same
      species were observed. Erythrocytes from all species, except for goats, supported
      intracellular development of newly invaded merozoites and high numbers of
      duplicated parasites, located in a morphologically normal accole position, were
      present. Only in bovine erythrocytes did subsequent rounds of invasion, leading
      to increased parasitaemia, take place. This suggests that host specificity is
      determined by factors operating late in the erythrocytic stage of the B. bovis
      life cycle. Incubation of erythrocytes with neuraminidase prior to invasion led
      to a decrease in invasion efficiency of approximately 80%. This effect was
      observed for several species. The removal of either alpha(2-3)-linked or alpha(2
      6)-linked sialic acid residues gave similar levels of reduction whereas
      simultaneous removal did not show an additive effect. Pre-incubation of
      merozoites with N-acetylneuraminyl-lactose decreased invasion efficiency by
      approximately 45% whereas addition just prior to invasion had no significant
      effect. The results demonstrate that invasion is dependent on the presence of
      sialic-acid containing membrane receptors on erythrocytes that interact with
      merozoite ligands that are probably already accessible during pre-incubation
      prior to invasion.

PMID- 14636676
TI  - Analysis of the SAG5 locus reveals a distinct genomic organisation in virulent
      and avirulent strains of Toxoplasma gondii.
AB  - We have recently characterised, in the virulent strain RH of Toxoplasma gondii,
      three glycosylphosphatidylinositol-anchored surface antigens related to SAG1
      (p30) and encoded by highly homologous, tandemly arrayed genes named SAG5A, SAG5B
      and SAG5C. In the present study, we compared the genomic organisation of the SAG5
      locus in strains belonging to the three major genotypes of T. gondii. Southern
      blot analysis using a SAG5-specific probe produced two related but distinct
      hybridisation patterns, one exclusive of genotype I virulent strains, the other
      shared by avirulent strains of either genotype II or genotype III. To understand
      the molecular bases of this intergenotypic heterogeneity, we cloned and sequenced
      the SAG5 locus in the genotype II strain Me49. We found that in this isolate the
      SAG5B gene is missing, with SAG5A and SAG5C laying contiguously. This genomic
      arrangement explains the hybridisation profiles observed for all the avirulent
      strains examined and indicates that the presence of SAG5B is a distinctive trait
      of genotype I. Furthermore, we identified two novel SAG1-related genes, SAG5D and
      SAG5E, mapping respectively 1.8 and 4.0 kb upstream of SAG5A. SAG5D is
      transcribed in tachyzoites and encodes a polypeptide of 362 amino acids sharing
      50% identity with SAG5A-C, whereas SAG5E is a transcribed pseudogene. We also
      evaluated polymorphisms at the SAG5 locus by comparing the coding regions of
      SAG5A-E from strains representative of the three archetypal genotypes. In
      agreement with the strict allelic dimorphism of T. gondii, we identified two
      alleles for SAG5D, whereas SAG5A, SAG5C and SAG5E were found to be three distinct
      nucleotide variants. The higher intergenotypic polymorphism of SAG5A, SAG5C and
      SAG5E suggests that these genes underwent a more rapid genetic drift than the
      other members of the SAG1 family. Finally, we developed a new PCR-restriction
      fragment length polymorphism method based on the SAG5C gene that is able to
      discriminate between strains of genotype I, II and III by a single endonuclease
      digestion.

PMID- 14636677
TI  - The intestinal parasite Pomphorhynchus laevis (Acanthocephala) interferes with
      the uptake and accumulation of lead (210Pb) in its fish host chub (Leuciscus
      cephalus).
AB  - Uninfected chub as well as fish experimentally infected with the acanthocephalan
      parasite Pomphorhynchus laevis were exposed to (210)Pb(2+) for up to 38 days and
      the uptake and distribution of lead within different fish organs and the
      parasites was determined at various time points. Highest metal concentrations
      were detected in the acanthocephalans, followed by intestine, bile, liver, gill
      and muscle of the fish host. Infected chub had significantly lower (210)Pb levels
      in the gills on day 17 (P< or =0.01), in the bile on day 24 (P< or =0.05) and in
      the gills as well as in the intestine on day 38 compared with uninfected fish. A
      subsequent polynomial regression revealed that lead levels for the infected fish
      ranged below the levels determined for uninfected fish during most of the
      exposure period. This is the first proof that P. laevis reduces lead levels in
      the bile thereby diminishing or even impeding the hepatic intestinal cycling of
      lead, which may reduce the amount of metals available for the fish organs. This
      is especially important for ecotoxicological research. For example, organisms
      used as accumulation indicators may erroneously indicate low levels of pollution
      if they are infected with parasites which alter their pollutant uptake
      mechanisms. Additionally, the results gave further experimental evidence for
      acanthocephalans as accumulation indicators for metals.

PMID- 14636678
TI  - A general test of the interactive-isolationist continuum in gastrointestinal
      parasite communities of fish.
AB  - Parasite communities are generally believed to lie somewhere along the
      interactive-to-isolationist continuum, i.e. from rich assemblages of species with
      high colonisation rates in which interspecific interactions play an important
      structuring role, to species-poor assemblages where interactions are unlikely.
      This framework has become one of the paradigms of parasite community ecology.
      There is, however, no objective way of ranking a set of parasite communities in
      terms of the extent of interactivity among their constituent species. Here, we
      propose a simple index of interactivity based on the general likelihood of
      species co-occurrence, and thus on the potential for interactions, and we apply
      it to component communities of gastrointestinal helminth parasites from 37
      species of marine fish hosts. The index essentially collapses several features of
      parasite communities thought to influence the degree of interactivity into a
      single number independent of the number of hosts examined or the total number of
      species in a component community. The range of values obtained here suggests that
      the potential interactivity in helminth communities of fish covers almost the
      full spectrum of possibilities, i.e. from isolationist to highly interactive
      communities. Although derived from presence/absence data only, the index
      correlates relatively strongly with the total parasite abundance per host, as
      well as the total prevalence of infection and the mean infracommunity richness.
      In other words, it captures properties of the community that influence
      interactivity. The use of the index in comparative studies may help in
      determining whether interactive helminth communities are, as widely believed,
      more common in endothermic vertebrate hosts than in fish hosts.

PMID- 14636679
TI  - Regional distribution of bovine Neospora caninum infection in the German state of
      Rhineland-Palatinate modelled by Logistic regression.
AB  - To obtain a rapid overview over the distribution of bovine Neospora caninum
      infections in the German state of Rhineland-Palatinate, an ELISA to determine
      specific bovine antibodies against a p38 surface antigen of N. caninum
      tachyzoites was modified to examine bulk milk samples from cattle herds.
      Experimental bulk milk samples were used to demonstrate that the seroprevalence
      in a group of animals can be estimated with this ELISA. A cut-off was selected
      for the specific detection of herds having a seroprevalence > or =10%. About 90%
      of the dairy herds located in Rhineland-Palatinate were examined. An overall
      prevalence of bulk milk-positive herds of 7.9% (95% confidence interval 7.0
      8.9%), respectively, was determined. Major regional differences in the
      distribution of bulk milk-positive herds were observed. Prevalences were higher
      in regions with an increased degree of urbanisation. Logistic regression was
      applied to model the prevalence of bulk milk-positive herds on a district and
      city level. Variables describing the dog density, mean temperature in July, mean
      temperature in January and the total yearly precipitation in districts and cities
      were able to explain most of the observed variability in the regional
      prevalences. Our results provide evidence that in addition to risk factors
      related to individual farms also risk factors related to the farm location such
      as dog density in the surrounding and climate factors are important in the
      epidemiology of bovine neosporosis.

PMID- 14636680
TI  - A panel of microsatellite and minisatellite markers for the characterisation of
      field isolates of Theileria parva.
AB  - Mini- and microsatellite sequences show high levels of variation and therefore
      provide excellent tools for both the genotyping and population genetic analysis
      of parasites. Herein we describe the identification of a panel of 11 polymorphic
      microsatellites and 49 polymorphic minisatellites of the protozoan haemoparasite
      Theileria parva. The PCR products were run on high resolution Spreadex gels on
      which the alleles were identified and sized. The sequences of the mini- and
      microsatellites were distributed across the four chromosomes with 16 on
      chromosome 1, 12 on chromosome 2, 14 on chromosome 3 and 18 on chromosome 4. The
      primers from the 60 sequences were tested against all the Theileria species that
      co-infect cattle in East and Southern Africa and were found to be specific for T.
      parva. In order to demonstrate the utility of these markers, we characterised
      eight tissue culture isolates of T. parva isolated from cattle in widely
      separated regions of Eastern and Southern Africa (one from Zambia, one from
      Uganda, two from Zimbabwe, four from Kenya) and one Kenyan tissue culture isolate
      from Cape buffalo (Syncerus caffer). The numbers of alleles per locus range from
      three to eight indicating a high level of diversity between these geographically
      distinct isolates. We also analysed five isolates from cattle on a single farm at
      Kakuzi in the central highlands of Kenya and identified a range of one to four
      alleles per locus. Four of the Kakuzi isolates represented distinct multilocus
      genotypes while two exhibited identical multilocus genotypes. This indicates a
      high level of diversity in a single population of T. parva. Cluster analysis of
      multilocus genotypes from the 14 isolates (using a neighbour joining algorithm)
      revealed that genetic similarity between isolates was not obviously related to
      their geographical origin.

PMID- 14636681
TI  - A virulence attenuated amoebapore-less mutant of Entamoeba histolytica and its
      interaction with host cells.
AB  - Entamoeba histolytica, the protozoan parasite which causes amoebiasis, is an
      exclusively human pathogen so developing a vaccine could effectively impact the
      spread of the disease. Recently we developed a genetically modified avirulent
      strain, termed G3, from the virulent E. histolytica strain HM-1:IMSS. The new
      strain lacks the important virulence factor, the amoebapore-A. The objective of
      our current study was to investigate the avirulence of the attenuated strain as
      well as to examine the antigenic and immunogenic responses of these trophozoites
      as potential candidates for a live vaccine. Functional assays were conducted to
      characterise the virulent behaviour of the G3 strain. This behaviour was compared
      to the virulent strain HM-1:IMSS and the non-virulent strain Rahman. Western
      blots were conducted to confirm the lack of amoebapore-A in the E. histolytica G3
      strain and to demonstrate that it had no influence on the presence of other
      virulence factors. Results of these two sets of tests proved the G3 strain to be
      phenotypically similar to the avirulent Rahman strain while antigenically
      identical to the virulent HM-1:IMSS, apart from the lack of the amoebapore-A
      protein. Intraperitoneal immunisation of hamsters with G3 trophozoites compared
      to sham immunised hamsters resulted in IgG anti-HM-1:IMSS antibodies. The level
      of humoral response was variable and further testing has to take place before
      introducing this new strain as a vaccine.

PMID- 14636682
TI  - Identification and characterisation of two distinct Smad proteins from the fox
      tapeworm Echinococcus multilocularis.
AB  - Members of the transforming growth factor-beta (TGF-beta) family of cytokines and
      their corresponding receptors regulate cellular key processes such as
      proliferation and differentiation, and could be involved in communication
      mechanisms between parasitic helminths and their hosts. A pivotal role in
      intracellular TGF-beta signalling is played by Smad factors which directly
      transmit incoming signals from the cell surface receptors to the nucleus. In this
      study, we have identified and characterised two novel members of the Smad family,
      EmSmadA and EmSmadB, which are expressed by the human parasite Echinococcus
      multilocularis. Based on amino acid sequence comparisons, both echinococcal Smad
      homologues could be classified as members of the R-Smad subfamily. EmSmadB showed
      a typical domain structure consisting of conserved MH1 and MH2 domains separated
      by a proline-rich linker region. EmSmadA, on the other hand, lacked an MH1 region
      and merely contained an MH2 domain, a feature which has so far not been described
      for R-Smads. Based on the structures of the corresponding chromosomal loci and on
      sequence features of the conserved L3 loop regions, EmSmadA and EmSmadB are most
      likely involved in the transmission of TGF-beta- and bone morphogenetic protein
      (BMP) signals, respectively. Yeast two-hybrid analyses revealed that both
      Echinococcus Smads are capable of homo- and heterodimer formations. However,
      while the formation of homodimers for EmSmadB required previous activation of the
      protein at the C-terminal SSVS motif, EmSmadA homodimers were already formed in
      the basal state of the factor. Upon expression of the Echinococcus Smads in human
      cells, EmSmadA, but not EmSmadB, was phosphorylated by the human TGF-beta type I
      receptor. Furthermore, both factors functionally interacted with human BMP
      receptors. By reverse transcriptase-PCR experiments, the encoding genes, emsmadA
      and emsmadB, were shown to be expressed in the larval stages metacestode and
      protoscolex during an infection of the intermediate host. Taken together, our
      data suggest an involvement of EmSmadA and EmSmadB in echinococcal developmental
      processes during natural infections and provide a solid basis for further
      investigations on TGF-beta signalling mechanisms in cestodes.

PMID- 14636683
TI  - Speciation and host-parasite relationships in the parasite genus Gyrodactylus
      (Monogenea, Platyhelminthes) infecting gobies of the genus Pomatoschistus
      (Gobiidae, Teleostei).
AB  - Using species-level phylogenies, the speciation mode of Gyrodactylus species
      infecting a single host genus was evaluated. Eighteen Gyrodactylus species were
      collected from gobies of the genus Pomatoschistus and sympatric fish species
      across the distribution range of the hosts. The V4 region of the ssrRNA and the
      internal transcribed spacers encompassing the 5.8S rRNA gene were sequenced; by
      including published sequences a total of 30 species representing all subgenera
      were used in the data analyses. The molecular phylogeny did not support the
      morphological groupings into subgenera as based on the excretory system,
      suggesting that the genus needs systematic revisions. Paraphyly of the total
      Gyrodactylus fauna of the gobies indicates that at least two independent
      colonisation events were involved, giving rise to two separate groups, belonging
      to the subgenus Mesonephrotus and Paranephrotus, respectively. The most recent
      association probably originated from a host switching event from Gyrodactylus
      arcuatus, which parasitises three-spined stickleback, onto Pomatoschistus gobies.
      These species are highly host-specific and form a monophyletic group, two
      possible "signatures" of co-speciation. Host specificity was lower in the second
      group. The colonising capacity of these species is illustrated by a host jump
      from gobiids to another fish order (Anguilliformes), supporting the hypothesis of
      a European origin of Gyrodactylus anguillae and its intercontinental introduction
      by the eel trade. Thus, allopatric speciation seems to be the dominant mode of
      speciation in this host-parasite system, with a possible case of sympatric
      speciation.

PMID- 14636684
TI  - Effect of flavan-3-ols on in vitro egg hatching, larval development and viability
      of infective larvae of Trichostrongylus colubriformis.
AB  - The effects of flavan-3-ols (the monomer units of condensed tannins (CT)) and
      their galloyl derivatives on the viability of eggs, the development of first
      stage (L1) larvae, and the viability of the infective larvae of Trichostrongylus
      colubriformis were investigated under in vitro conditions. Each of the flavan-3
      ol gallates showed some inhibition of egg hatching at 100 microg/ml, and 100%
      inhibition at 1000 microg/ml, with epigallocatechin gallate being the most
      effective in the egg hatch (EH) assay. In contrast, none of the flavan-3-ols were
      able to completely inhibit egg hatching. The flavan-3-ols and galloyl derivatives
      dose-dependently inhibited the development of infective larvae as assessed by the
      larval development (LD) assay. A larval migration inhibition (LMI) assay was used
      to assess the effect of flavan-3-ols and their galloyl derivatives on the
      motility of the infective third-stage (L3) larvae of T. colubriformis. In
      general, the flavan-3-ol gallates were more effective than the flavan-3-ols at
      immobilising the infective larvae as evidenced by their ability to inhibit more
      (P<0.05-0.01) larvae from passing through the LMI sieves. At 500 microg/ml,
      epigallocatechin gallate inhibited significantly more (P<0.1) larvae from passing
      through the sieves than did catechin gallate, epicatechin gallate, or
      gallocatechin gallate. Comparisons were made between the flavan-3-ols and their
      galloyl derivatives with the in vitro effects of CT extracts from several forage
      legumes, which have exhibited effects on parasites in vivo. The forage legumes
      tested at 200-500 microg/ml reduced the proportion of eggs that hatch, with
      comparable results to those obtained using the flavan-3-ols. The activities may
      be influenced by the prodelphinidin: procyanidin (PD:PC) ratios: CT extracts from
      Lotus pendunculatus and sainfoin have PD:PC ratios of 70:30 and 77:23,
      respectively, whereas the less active CT extract from Lotus corniculatus has a
      PD:PC ratio of 27:73. The active CT extracts from forage legumes have
      epigallocatechin as the dominant flavan-3-ol extender unit, and epigallocatechin
      is the most active flavan-3-ol in both the EH and LD assays.

PMID- 14636685
TI  - Cryptosporidium and Giardia-zoonoses: fact or fiction?
AB  - Giardia and Cryptosporidium are enteric protozoan parasites that infect a wide
      range of vertebrate hosts. Both are transmitted either by direct faecal/oral
      contact or by the ingestion of contaminated food or water. The discovery of
      morphologically similar organisms infecting humans and a variety of mammals and
      birds has led to the proposal that both Cryptosporidium and Giardia are zoonotic
      (i.e. transmitted in nature between humans and animals). Transmission between
      humans and animals has been supported by cross-infection studies. However, closer
      examination of many of these studies reveals limitations in the methodologies
      utilised. More recent molecular genetic studies have demonstrated considerable
      genetic diversity among isolates of the same species of Giardia and
      Cryptosporidium, suggesting that these species are in fact species complexes and
      that some of these novel species may be host-specific. This paper will critically
      examine the evidence for the zoonotic transmission of these parasites.

PMID- 14636686
TI  - Genetic similarity of Puumala viruses found in Finland and western Siberia and of
      the mitochondrial DNA of their rodent hosts suggests a common evolutionary
      origin.
AB  - A total of 678 small mammals representing eight species were trapped in western
      Siberia in 1999-2000 and assayed for the presence of hantaviruses. Eighteen
      animals, all Clethrionomys species, were antigen positive by enzyme-linked
      immunosorbent assay (ELISA). Small and medium genome segments were recovered by
      RT-PCR from six samples from Clethrionomys glareolus and three from Clethrionomys
      rufocanus. Sequence comparison and phylogenetic analysis revealed that these
      hantaviruses were Puumala virus and were similar to hantavirus strains from
      Finland. To confirm these data, partial nucleotide sequences of the rodent hosts'
      cytochrome b genes were obtained, as well as several sequences from genes from
      rodents trapped at different localities of European Russia and western Siberia.
      The cytochrome b sequences of Siberian bank voles were similar to sequences of C.
      glareolus, trapped in Finland. These data suggest that the Puumala hantaviruses,
      as well as their rodent hosts, share a common evolutionary history. We propose
      that these rodents and viruses may be descendents of a population of bank voles
      that expanded northward from southern refugia during one of the interglacial
      periods.

PMID- 14636687
TI  - Maintenance of aphid clonal lineages: images of immortality?
AB  - Artificial cloning and ancient asexuals have impacted upon both scientific and
      lay thinking in applied and theoretical fields as diverse as medicine and
      evolution. Hence, this is an opportune time to promote debate and discussion on
      what maintains a clonal lineage. The genetic fidelity of a clone has been
      discussed in detail elsewhere [Genet. Res. 79 (2002) 1; Biol. J. Linnean Soc. 79
      (2003) 3]. In this paper, we focus on the lineage integrity (=longevity), or
      physiological lifespan of a clone with respect to senesce in relation to factors
      controlling telomere functioning. Aspects of cell line research pertinent to
      eukaryotic clonal lineages are discussed and, in particular, we try to
      extrapolate aspects of this research and apply it to apomictic (=mitotic) aphid
      lineages to suggest how they may be maintained. Analogies are made between single
      cells and individual aphids that senescence through a generation, whilst the
      respective lineages persist for finite periods, unless that is, compensatory
      mechanisms have evolved allowing immortality in the one and ancient asexuality in
      the other. Such comparison may allow fresh insights into the mechanisms of clonal
      lineage maintenance and evolution. We hypothesise that: (1). the cause of
      extinction in eukaryotic clonal lineages is due to deleterious effects on key
      regions of the genome, the chromosomal telomere being one such site; (2).
      recombination acts as a common mechanism to reset telomere functioning, perhaps
      more fundamental than its utility to reduce genetic load and maintain
      adaptability; and (3). ancient lineages persist through time as a function of
      group-specific compensatory mechanisms that maintain telomere integrity.

PMID- 14636688
TI  - The use of specific and generic primers to identify trypanosome infections of
      wild tsetse flies in Tanzania by PCR.
AB  - The accurate identification of trypanosome species and subspecies remains a
      challenging task in the epidemiology of human and animal trypanosomiasis in
      tropical Africa. Currently, there are specific PCR tests to identify about 10
      different species, subspecies or subgroups of African tsetse-transmitted
      trypanosomes. These PCR tests have been used here to identify trypanosomes in
      four species of tsetse (Glossina brevipalpis, G. pallidipes, G. swynnertoni, G.
      morsitans morsitans) from two areas of Tanzania. PCR using species-specific
      primers was performed on 1041 dissection-positive proboscides, giving an overall
      positive identification in 254 (24%). Of these, 61 proboscides (24%) contained
      two or more trypanosomes. The trypanosome with the greatest overall prevalence at
      both field sites was Trypanosoma simiae Tsavo, which was identified in a total of
      118 infected tsetse proboscides (46%). At Pangani, T. godfreyi was found in G.
      pallidipes but not in G. brevipalpis, suggesting that these flies might have
      different susceptibility to this trypanosome or might have fed on a different
      range of hosts. A high proportion (about 75%) of trypanosome infections remained
      unidentified. To investigate the identity of these unidentified samples, we used
      primers complementary to the conserved regions of trypanosomal small subunit
      ribosomal RNA (ssu rRNA) genes to amplify variable segments of the gene.
      Amplified DNA fragments were cloned, sequenced and compared with ssu rRNA genes
      on database of known trypanosome species. In this way, we have tentatively
      identified two new trypanosomes: a trypanosome related to Trypanosoma vivax and a
      trypanosome related to T. godfreyi. The T. godfreyi-related trypanosome occurred
      frequently in the Tanzanian field samples and appears to be widespread. Molecular
      identification of these two new trypanosomes should now facilitate their
      isolation and full biological characterisation.

PMID- 14636689
TI  - Pneumocystis jiroveci in Portuguese immunocompromised patients: association of
      specific ITS genotypes with treatment failure, bad clinical outcome and
      childhood.
AB  - We analyzed the genetic variation among isolates of Pneumocystis jiroveci from
      Portuguese immunocompromised patients with PCP at the internal transcribed spacer
      (ITS) regions of the nuclear rRNA operon and at the dihydropteroate synthase
      (DHPS) gene. Pulmonary secretions from 42 patients with PCP corresponding to 43
      episodes were studied. Demographic, immunological, and clinical data were
      obtained from all patients. By combining the two regions ITS1 and ITS2, we found
      17 different ITS types of P. jiroveci, two of them were new types (Pb and Pe).
      The four most prevalent ITS types were Eg (23.3%), Eb and Ne (11.6% each), and Bi
      (9.3%). A single type was detected in 95.3% of the samples and 4.7% had mixed
      infections with three different ITS types. DHPS mutants were present in 17 (46%),
      and the wildtype was present in 20 (54%) of 37 isolates. No association was found
      between ITS and DHPS types and between DHPS types and therapy or response to anti
      PCP treatment. Type Ne presented an association with negative response to anti
      PCP treatment (P<0.001) and with death before 120 days after PCP diagnosis
      (P=0.025). Type Eb was significantly more common in children than in adults
      (P=0.001). Our data suggest an association of specific ITS genotypes with
      treatment failure, bad clinical outcome and childhood.

PMID- 14636690
TI  - Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 mutations in Plasmodium
      falciparum and in vitro/in vivo chloroquine resistance in Burkina Faso, West
      Africa.
AB  - The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in Plasmodium
      falciparum was explored in samples from patients with uncomplicated malaria and
      tested in vitro and in vivo with chloroquine (CQ) in Burkina Faso. The two
      mutations were strongly related. The Pfcrt T76 mutation was found in 82% of the
      samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7
      13.3]; P=0.002). However, only half (16/34) of samples with Pfcrt T76 mutation
      had also the Pfmdr-1 Y86 mutation. The latter was apparently associated with in
      vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association
      disappeared (P=0.77) after adjusting for the presence of the Pfcrt T76 mutation.
      This suggests that the occurrence of the Pfmdr-1 Y86 mutation is dependent on
      that of Pfcrt T76 mutation and could explain previous reports linking the Pfmdr-1
      Y86 mutation with CQ resistance (CQR). The isolates carrying both the Pfcrt K76
      and Pfmdr-1 N86 alleles (wild/wild (WW)) and the single mutant Pfmdr-1 Y86 (WM)
      had the lowest IC50 geometric mean (GMIC50) values, while those carrying both
      Pfcrt T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single mutant Pfcrt
      T76 (MW) had the highest. Among pre-treatment samples there was a strong linkage
      disequilibrium with an excess of MM and WW and a deficit of single mutants (MW
      and WM), suggesting that parasite fitness is higher for the former and lower for
      the latter.

PMID- 14636691
TI  - More about the Viking hypothesis of origin of the delta32 mutation in the CCR5
      gene conferring resistance to HIV-1 infection.
AB  - The chemokine receptor CCR5 constitutes the major coreceptor for the HIV-1,
      because a mutant allele of the CCR5 gene named delta32 was shown to provide to
      homozygotes a strong resistance against infection. In the present study the
      frequency of the delta32 allele was collected in 36 European populations and in
      Cyprus, and the highest allele frequencies were found in Nordic countries. We
      constructed an allele map of delta32 frequencies in Europe; the map is in
      accordance to the Vikings hypothesis of the origin of the mutation and his
      dissemination during the eighth to the tenth centuries.

PMID- 14636692
TI  - Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats:
      analysis of dose-response following topical induction and time course following
      repeated inhalation challenge.
AB  - Trimellitic anhydride (TMA) is a low-molecular-weight chemical known to cause
      occupational asthma. The dose-response study was designed to determine whether
      respiratory responses during a single inhalation challenge with TMA (25-30 mg/m3
      for 30 min, 3 weeks after the initial induction), the ensuing non-specific airway
      hyperresponsiveness (AH) to methacholine (MCh) aerosol, and infiltration of
      eosinophilic granulocytes into the lungs of sensitized Brown Norway (BN) rats are
      associated and dependent on the concentration of TMA used for topical induction.
      The initial topical exposure concentrations were 1, 5, and 25% TMA in
      acetone:olive oil (AOO) followed by a booster induction 1 week later. In the time
      course study BN rats received AOO alone or were sensitized to the minimal
      sensitizing topical concentration of TMA (5%) and were the subsequently
      challenged with TMA on Days 17, 24, 41, 47, 55, and 66, followed by a MCh
      challenge 1 day later. One additional group of rats was sensitized to 5% TMA but
      were repeatedly challenged with MCh without prior TMA challenge. In the dose
      response study the rats sensitized topically to TMA (5 and 25% in AOO) displayed
      unequivocal changes in breathing patterns upon challenge with TMA, including an
      increased responsiveness to MCh aerosol. These findings were associated with a
      sustained pulmonary eosinophilic inflammation. All endpoints demonstrated
      consistently that 5% TMA in AOO constitutes the minimal sensitizing
      concentration. When rats were topically sensitized with this concentration and
      repeatedly challenged with TMA over a time period of 7 weeks, it became apparent
      that challenge exposures in BN rats may be false negative when performed at time
      periods less than 3 weeks after the initial induction. Despite the time-related
      increased responsiveness elicited by the repeated TMA challenge exposures, the
      MCh challenge revealed increased non-specific airway hyperreactivity exclusively
      on Day 17. After the sixth TMA-challenge, the respiratory response and lung
      weights of rats sensitized topically were essentially similar to those observed
      in the repetitively re-challenged control group (induction: vehicle only;
      repeated booster challenge exposures with TMA). Thus, it appears, that in this
      animal model the effective concentration for successful topical sensitization
      must be at least approximately 5%. The repeated low-dose re-challenge with TMA in
      topically sensitized rats resulted in similar or slightly aggravated time-related
      responses over a period of 7 weeks. An over-proportionally increased
      susceptibility of rats receiving a topical priming dose prior to repeated
      inhalation challenge exposures was not observed. In summary, this study shows
      that the analysis of functional changes in breathing patterns is suitable to
      identify respiratory allergy. Repeated short-term inhalation exposures to mildly
      irritant concentrations (but low doses) of chemical asthmagens may be of higher
      concern than topical exposures.

PMID- 14636693
TI  - Cadmium directly induced the opening of membrane permeability pore of
      mitochondria which possibly involved in cadmium-triggered apoptosis.
AB  - The mitochondrial damage induced by cadmium has been well established, but its
      mechanism and its relationship with cadmium-induced apoptosis are elusive until
      now. Our research showed that cadmium could directly lead to the dysfunction of
      isolated mitochondria from mouse liver, including the inhibition of respiration,
      the opening of permeability transition pore (PTP), the loss of transmembrane
      potential, and the release of cytochrome c. These mitochondrial changes were
      completely suppressed by Bcl-xL and Ruthenium Red (RR). Bongkrekic acid (BK), an
      inhibitor of the PTP opening directly via adenine nucleotide translocator (ANT),
      also completely inhibited the PTP opening and loss of transmembrane potential.
      However, cyclosporin A (CsA), another inhibitor of the PTP opening indirectly via
      ANT, had not any inhibitory effect. When cadmium being pre-incubated with
      proteins containing abundant thiol groups, its effect was partially reversed.
      These results revealed that mitochondria pathway may involve in cadmium-induced
      apoptosis, and cadmium caused the PTP opening possibly through its binding to
      thiol groups of ANT. Furthermore, the mechanism of the PTP opening induced by
      cadmium was probably distinct from that of the calcium-induced PTP opening.

PMID- 14636694
TI  - Co-localized expression of FasL, Fas, Caspase-3 and apoptotic DNA fragmentation
      in mouse testis after oral exposure to di(2-ethylhexyl)phthalate.
AB  - Expression of apoptosis-related proteins FasL, Fas and Caspase-3, as well as DNA
      fragmentation were examined in mouse testis 12 h after exposure to 4-0.004 mg/g
      di(2-ethylhexyl)phthalate (DEHP). Immunocytochemical examination of the highest
      dose (4 mg/g DEHP) mouse revealed a distribution of FasL in Sertoli cell and Fas
      in nearby spermatocyte, and Fas and Caspase-3 in the same spermatocyte. Fas
      positive spermatocytes had a DNA-fragmented nucleus detectable by terminal
      deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL)
      method. After exposure to 4, 0.4, 0.04 or 0.004 mg/g DEHP, the maximum number of
      nuclei with fragmented DNA per 0.5 microm testis section was 22, 7, 5 and 3,
      respectively. In unexposed control the maximum number was 3. To further estimate
      total amount of the fragmented DNA in testis of the exposed mouse, the extracted
      DNA fragments were analyzed by agarose gel electrophoresis. The amount of
      fragments in the first three steps of the DNA ladder was estimated by a photo
      densitometry. In the highest dose mouse (4 mg/g DEHP), the fragmented DNA was 2.2
      times as much in the control. In lower dose mouse (0.4, 0.04 or 0.004 mg/g DEHP),
      it was 1.1 times as much in the control. Taken together, these observations
      suggest that a single oral exposure to DEHP as low as 0.04 mg/g might be
      effective to testicular DNA fragmentation and apoptosis.

PMID- 14636695
TI  - Effect of UV screens and preservatives on vitellogenin and choriogenin production
      in male medaka (Oryzias latipes).
AB  - Ultra violet (UV) screens and preservatives are widely and increasingly used in
      cosmetics and pharmaceuticals. In the present study, we examined the
      estrogenicity of 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate
      (OMC), and propyl paraben (n-propyl-p-hydroxy-benzoate; PP), among UV screens and
      preservatives, using male medaka (Oryzias latipes), in regard to production of
      vitellogenin (VTG) and choriogenin (CHG) which are known to be estrogen
      responsive gene products. First, using a VTG enzyme-linked immunosorbent assay
      (ELISA) system, we determined the increase in VTG plasma concentration in medaka
      due to exposure to 4-MBC, OMC, and PP, and compared this concentration to the non
      treated control. Next, we found increases in mRNA expression levels of VTG
      subtypes VTG-1 and VTG-2, and CHG subtypes CHG-L and CHG-H, in liver due to
      exposure to 4-MBC, OMC, and PP compared to the non-treated control. In addition,
      we also found increased mRNA expression levels of estrogen receptor (ER) alpha,
      among sex hormone receptors in the liver, due to exposure to 4-MBC, OMC, and PP
      compared to the non-treated control. In this study, we showed that 4-MBC, OMC,
      and PP have estrogenic activity in fish.

PMID- 14636696
TI  - Carbon monoxide neurotoxicity: transient inhibition of avoidance response and
      delayed microglia reaction in the absence of neuronal death.
AB  - Carbon monoxide exposure produces neurobehavioral effects associated with the
      level of carboxyhemoglobin (COHb) in the blood. A threshold has been proposed of
      approximately 35% COHb for the manifestation of disruption in neurobehavioral
      tasks. The effects of CO exposure producing 30-40% carboxyhemoglobin (COHb)
      levels in young adult male Fischer 344 rats were examined with regard to clinical
      signs of toxicity, performance on a previously learned avoidance procedure, and
      neuronal and glia histopathology. High levels of exposure (4000 ppm) for 15 min
      were imposed on either a background blood COHb level of 5% produced by a 2 h
      exposure to 50 ppm CO or a control background from conditioned-air exposure. Upon
      removal from the nose-only inhalation holder, signs of mild lethargy and
      decreased activity were evident for 2 min for conditioned-air controls and 50 ppm
      CO exposure groups and 3-4 min following 4000 ppm CO. Performance on a two-way
      shuttle box active avoidance task showed no differences between 50 ppm CO rats
      and conditioned-air controls while the 4000 ppm CO exposed groups showed a
      significant decrease in avoidance and escape responses. Histological examination
      showed no evidence of delayed neuronal death or astrocyte reactivity in the
      hippocampus or cerebellum; however, a distinct focal staining of reactive
      microglia in both regions was evident in animals exposed to 4000 ppm CO. While 50
      ppm CO (5% COHb) alone produced no disruption in avoidance performance, microglia
      staining in the cerebellum was significantly increased over conditioned-air
      controls. This regional and focal response of microglia suggests the need for
      further study regarding such subtle cellular changes and their relationship with
      COHb levels.

PMID- 14636697
TI  - Parallelism and dissociation in the actions of an Aroclor 1260-based transformer
      fluid on testicular androgenesis and antioxidant enzymes.
AB  - The mechanism by which Aroclors and other polychlorinated biphenyls (PCBs)
      inhibit testicular androgenesis in vivo and in vitro has not been characterized.
      Here we studied in adult rats the effects of intratesticular (i.t.t.),
      intraperitoneal (i.p.) and by gavage (p.o.) administration of Pyralene, an
      Aroclor 1260-based transformer fluid, on testicular androgenesis and oxidative
      status in androgen-producing interstitial cells and liver. Pyralene markedly
      decreased in vitro agonist stimulated androgenesis 24 h after bilateral i.t.t.
      injection (25 microg/testis), 24 h and 96 h after single i.p.-injection (10 and
      50 mg/kg body weight), and 96 h after p.o.-administration (7x10 mg and 7x50 mg/kg
      body weight daily). Inhibited androgenesis was accompanied by changes in the
      activity of antioxidant enzymes (AOEs) in interstitial cells after local i.t.t.
      treatment and occasionally after systemic Pyralene application. Among changes in
      the activity, glutathione peroxidase and catalase reflected relatively well the
      toxicity of Pyralene in these cells. In liver, glutathione-S-transferase (GST)
      and glutathione peroxidase activities were enhanced after p.o.-treatment and
      total glutathione (tGSH) content and lipid peroxidation (LP) were enhanced after
      i.p.-administration. These results indicate that Pyralene inhibits androgenesis
      independently of the method of its administration. The results also suggest that
      changes in the oxidative status in testicular milieu are not critical for
      Pyralene-induced inhibition of androgenesis.

PMID- 14636698
TI  - Effects of currently used pesticides in the AhR-CALUX assay: comparison between
      the human TV101L and the rat H4IIE cell line.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates many of the biologic and toxicological effects of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. The in vitro chemically
      activated luciferase expression (CALUX) assay has been proven to be a rapid and
      sensitive assay for assessing the potency of AhR-activating compounds. We have
      used the AhR-CALUX assay to investigate the AhR-mediated activity of the
      persistent organochlorine insecticide dieldrin and twenty-two pesticides
      currently used in Denmark by employing the rat H4IIE and the human TV101L
      hepatoma cell lines. In comparison the results indicated that the rat H4IIE cell
      line is more sensitive than the human TV101L for detection of TCDD inducing AhR
      CALUX activity. The pesticides iprodione, chlorpyrifos and prochloraz showed dose
      dependent AhR agonistic effects in both cell lines at concentrations above 10, 1
      and 1 microM, respectively. However, some pesticides (methiocarb, chlorothalonil,
      tribenuron-methyl, paclobutrazol and tolchlofos-methyl) elicited differential
      responses in the two cell lines.

PMID- 14636699
TI  - Nitrotyrosine formation in splenic toxicity of aniline.
AB  - Splenic toxicity of aniline is characterized by vascular congestion, hyperplasia,
      fibrosis and development of a variety of sarcomas in rats. However, the
      mechanisms of this selective splenic toxicity are not well understood. Previously
      we showed that aniline exposure causes oxidative damage to spleen. To further
      explore the oxidative mechanisms of aniline toxicity, we evaluated the
      contributions of nitric oxide. Nitric oxide reacts with superoxide anion to form
      peroxynitrite, a powerful oxidant that converts the tyrosine residues of proteins
      to nitrotyrosine (NT). Therefore, aim of this study was to establish the role of
      nitric oxide through the formation and localization of NT in the spleen of rats
      exposed to aniline. Male Sprague-Dawley (SD) rats were given 1 mmol/kg per day
      aniline hydrochloride in water by gavage for 7 days, while the controls received
      water only. Immunohistochemical analysis for NT showed an intense staining in the
      red pulp areas of spleen from aniline-treated rats, localized in macrophages and
      sinusoidal cells. Occasionally mild NT immunostaining was also evident in the
      white pulp. Western blot analyses of the post-nuclear fraction of the spleens
      showed major nitrated proteins with molecular weights of 49, 30 and 18 kDa.
      Immunohistochemical analysis of inducible nitric oxide synthase (iNOS) also
      showed increased expression in the red pulp of the spleens from aniline-treated
      rats; the cellular localization was similar to nitrated proteins. These studies
      suggest that oxidative stress in aniline toxicity also includes aberration in
      nitric oxide production leading to nitration of proteins. Functional consequences
      of such nitration will further elucidate the contribution of nitric oxide to the
      splenic toxicity of aniline.

PMID- 14636700
TI  - Hematotoxicity response in rats by the novel copper-based anticancer agent:
      casiopeina II.
AB  - The in vivo toxicity of the novel copper-based anticancer agent, casiopeina II
      (Cu(4,7-dimethyl-1,10-phenanthroline)(glycine)NO3) (CII), was investigated.
      Casiopeinas are a family of copper-coordinated complexes that have shown
      promising anticancer activity. The major toxic effect attributed to a single i.v.
      administration of CII (5 mg/kg dose) in the rat was an hemolytic anemia (reduced
      hemoglobin concentration (HB), red blood cell (RBC) count and packed cell volume
      (PCV) accompanied by a marked neutrophilic leukocytosis) 12 h and 5 days after
      administration, attributed to a direct erythrocyte damage. Increased reticulocyte
      levels and presence of normoblasts in peripheral blood 5 days post-administration
      indicated an effective erythropoietic response with recovery at 15 days. Increase
      in spleen weight and the morphological evidence of congestion of the red pulp
      (RP) with erythrocytes (E) resulting in a higher ratio of red to white pulp (WP)
      was consistent with increased uptake of damaged erythrocytes by the
      reticuloendothelial system observed by histopathology and electron microscopy.
      Extramedullary hemopoiesis was markedly increased at 5 days giving further
      evidence of a regenerative erythropoietic response that had an effective recovery
      by 15 days. Morphological changes in spleen cellularity were consistent with
      hematotoxicity, mainly a reduction of the red pulp/white pulp ratio, increase in
      erythrocyte content at 12 h, and an infiltration of nucleated cells in the red
      pulp at 5 days, with a tendency towards recovery 15 days after administration.
      The erythrocyte damage is attributed to generation of free radicals and oxidative
      damage on the membrane and within cells resulting from the reduction of Cu(II)
      and the probable dissociation of the CII complex.

PMID- 14636701
TI  - The immune system of geriatric mice is modulated by estrogenic endocrine
      disruptors (diethylstilbestrol, alpha-zearalanol, and genistein): effects on
      interferon-gamma.
AB  - The immune system is a potential target for estrogenic endocrine disrupters. To
      date, there is limited information on whether estrogenic endocrine disruptors
      modulate the immune system of aged individuals. To address this issue, groups of
      74-week-old mice were given nine oral doses of selected estrogenic endocrine
      disrupters: diethylstilbestrol (DES, 3 microg/100 g bw), alpha-zearalanol (0.5
      mg/100 g bw), or genistein (0.15 mg/100 g bw) in corn oil, or corn oil alone,
      over 2.5 weeks. Both developmental (thymus) and mature (spleen) lymphoid organs
      were affected, although specific effects varied with the chemical. DES
      significantly decreased thymocyte numbers. However, relative percentages of
      thymocyte subsets were not altered. While splenic cellularity and percentages of
      T and B cells were unchanged, splenocytes from DES-exposed mice had significantly
      decreased ability to proliferate in response to Concanavalin-A (Con-A). Con-A
      activated splenocytes from mice treated with genistein or alpha-zearalanol had
      decreased levels of interferon-gamma (IFNgamma) protein in their culture
      supernatants compared to similar cultures from oil-treated mice. RT-PCR analysis
      of Con-A-activated splenocytes revealed that the expression of IFNgamma gene is
      altered by DES or genistein treatment. Together, these results suggest that
      estrogenic endocrine disruptors modulate the immune system of aged mice.

PMID- 14636702
TI  - A predictive F344 rat immunotoxicology model: cellular parameters combined with
      humoral response to NP-CgammaG and KLH.
AB  - The purpose of this study was to examine the predictive value of humoral and
      cellular immune parameters in determining the immunotoxic effects of the oral
      administration of azathioprine (AZA), cyclophosphamide (CY), or cyclosporin A
      (CsA) at doses of 25/17, 10, or 25 mg/kg per day, respectively, for 30 days in
      F344 female rats. The effect of these known immunosuppressive compounds on the
      immune response was assessed in a humoral model that consisted of the
      administration of nitrophenyl-chicken gamma globulin (NP-CgammaG) and keyhole
      limpet hemocyanin (KLH) antigens during immunosuppressive treatment and the
      measurement of resulting rat antigen-specific IgG and IgM, as well as total IgG,
      levels. Cellular assessment parameters were collected from the same groups of
      animals as the humoral parameters and included organ weights and cellularity,
      hematology, lymphocyte phenotype characteristics, spleen cell mitogen stimulation
      (T and B cell-dependent), splenic natural killer (NK) cell cytotoxicity, and bone
      marrow cellularity and lymphocyte phenotype differential. Although decreases in
      several of the cellular assay parameters were observed, the only functional
      assays to demonstrate a statistically significant immunosuppressive effect by all
      three immunosuppressive agents were the antigen-specific serum IgG levels. The
      primary (day 10; 15 days post-immunization) and secondary (day 25; 5 days post
      rechallenge) nitrophenyl (NP) responses were significantly suppressed by > or
      =60%. The use of NP hapten provided consistent responses when analyzed with a
      sensitive, well developed, ELISA methodology. Absolute lymphocyte phenotyping and
      lymphocyte hematology were also predictive of T cell immunosuppression for all
      three compounds. The data presented herein suggests that these two parameters, NP
      IgG humoral response and lymphocyte phenotyping, are sufficient for identifying
      immunosuppressive compounds.

PMID- 14636703
TI  - A murine model for low molecular weight chemicals: differentiation of respiratory
      sensitizers (TMA) from contact sensitizers (DNFB).
AB  - Exposure to low molecular weight (LMW) chemicals contributes to both dermal and
      respiratory sensitization and is an important occupational health problem. Our
      goal was to establish an in vivo murine model for hazard identification of LMW
      chemicals that have the potential to induce respiratory hypersensitivity (RH). We
      used a dermal sensitization protocol followed by a respiratory challenge with the
      evaluation of endpoints typically associated with RH in human disease.
      Trimellitic anhydride (TMA) was used as a prototype respiratory sensitizer and
      was compared to the dermal sensitizer; 2,4-dinitrofluorobenzene (DNFB), along
      with vehicle controls. BALB/c mice were dermally sensitized using two exposure
      protocols. Mice in both protocols were dermally exposed on experimental days; D
      18 and D-17 (abdomen), and D-13 (ear). On D 0 mice received an intratracheal (IT)
      challenge. The mice in Protocol 2 were abdominally exposed twice with the
      addition of exposures on D-25 and D-24. Results indicate that mice required the
      additional dermal sensitization and the IT challenge (Protocol 2) to
      significantly elevate total IgE in serum and bronchoalveolar lavage fluid (BALF).
      Additional responses suggestive of RH were seen following Protocol 2, including
      increases in BALF cell numbers and neutrophils post IT with TMA (but not DNFB).
      These data suggest that the dermal sensitization and IT challenge followed by
      evaluation of serum antibodies and lung parameters are a reasonable and
      logistically feasible approach towards the development of a model for RH
      responses to LMW chemicals.

PMID- 14636704
TI  - Developmental immunotoxicity of dexamethasone: comparison of fetal versus adult
      exposures.
AB  - Dexamethasone-21 phosphate was administered (s.c.) to pregnant CD rats at days 6
      21 of gestation (0, 0.0625, 0.125, 0.25, and 0.5 mg/kg/day) with identical
      exposure of non-pregnant adult females. Some reproductive (anogenital distance)
      and growth (body weight) measures of pups were altered. In the juvenile (5
      weeks), the delayed type hypersensitivity response to KLH was significantly
      reduced at all doses examined and this pattern continued into adulthood (13
      weeks). In contrast, the DTH response of adults exposed to DEX was unaltered even
      at the highest dose. Few DEX-induced changes were seen in offspring or adult
      blood parameters or in splenocytes analyzed for cell surface makers (by flow
      cytometry). The thymus of both exposed pups (both ages) and adults showed a
      marked reduction in the medulla/lobe area beginning with the 0.125 mg/kg/day DEX
      exposure level. Macrophage production of TNF and NO was only marginally affected
      as was splenocyte production of IL-4 and IFN-gamma. In contrast, pups assessed as
      juveniles were significantly depressed in splenic IL-2 and IL-10 production. DEX
      exposure altered serum antibody levels across age groups with an increase of KLH
      specific IgG (beginning with the 0.0125 mg/kg/day dose) while total IgE was
      reduced. These results suggest that while DEX exposure produces some common
      alterations following in utero versus adult exposure, fetal exposure (even at the
      lowest doses tested) produces marked and persistent functional loss (DTH) not
      evident in exposed adults. Furthermore, there was no apparent advantage in
      delaying immune assessment until the offspring reached adulthood.

PMID- 14636706
TI  - The influence of monoterpene synthase transformation on the odour of tobacco.
AB  - Monoterpenes are an important class of terpenoids that are commonly present in
      plant essential oils. These can be extracted from plants and are used in the
      flavouring and perfumery industry. Monoterpene synthases are the key enzymes in
      monoterpene biosynthesis, as they catalyse the cyclisation of the ubiquitous
      geranyl diphosphate (GDP) to the specific monoterpene skeletons. Tobacco is one
      of the most studied model plants, it can easily and efficiently be transformed,
      and is a suitable model to study the release of plant volatiles. Thus, we have
      isolated monoterpene synthases from lemon, transformed tobacco with these cDNAs
      and have used human panelists to study the change in fragrance of the transgenic
      in comparison to the wild type plants. In a triangle test, we found that subjects
      were capable of smelling significant differences between leaf samples. However,
      as a result of variability in panel ratings, no significant difference between
      two sets of transgenic flowers and the wild type tobacco flowers was found for
      the generated attributes in a descriptive test.

PMID- 14636705
TI  - Microbead display of proteins by cell-free expression of anchored DNA.
AB  - Gene expression technologies where nucleic acid sequences remain physically
      linked to their corresponding gene products are important tools for selection and
      identification of rare variants in large protein libraries. Here, we describe a
      gene expression system, which combines the potential of bead-based suspension
      array technology (SAT) with gene expression and clonal identification. Using
      streptavidin-coated polystyrene micrometer-sized beads as solid supports for
      anchored PCR products, we have investigated conditions for cell-free expression
      and bioaffinity technology to provide clonal co-anchoring of corresponding gene
      products. Experiments showed that coupled transcription and translation of PCR
      product expression cassettes resulted in display of affinity-anchored proteins
      whose binding characteristics could be analyzed via direct and selective
      interaction with a fluorescently labeled target protein. Interestingly,
      experiments performed with differently biotinylated PCR products showed that the
      efficiency of display was dependent on the directionality of the expression
      cassette relative to the bead surface. In spiked systems, using small
      immunoglobulin binding proteins as models, we demonstrate efficient flow
      cytometric sorting of beads corresponding to the target interacting clones,
      verified by post-sorting analysis and clonal identification at DNA level. The use
      of this technology, including alternative formats, for different proteomics
      applications is discussed.

PMID- 14636707
TI  - The role of the Aspergillus niger furin-type protease gene in processing of
      fungal proproteins and fusion proteins. Evidence for alternative processing of
      recombinant (fusion-) proteins.
AB  - We have characterized growth and protein processing characteristics of
      Aspergillus niger strains carrying a disrupted allele of the previously cloned
      and characterized kexB gene [Appl. Environ. Microbiol. 66 (2000) 363] encoding a
      furin-type endoprotease. Deletion of the single-copy gene confirms it to be non
      essential but disruptant strains exhibit a morphologically distinct phenotype
      characterized by hyperbranching. Processing of homologous pro-proteins and fusion
      proteins comprised of a heterologous protein fused down-stream of glucoamylase
      and separated at the fusion junction by an endoproteolytic cleavage site was
      compared in wildtype and mutant strains of A. niger. We show that maturation of
      the native glucoamylase requires KexB, whereas maturation of aspergillopepsin
      does not. The processing of fusion proteins carrying Lys-Arg requires KexB,
      although alternative endoproteases are capable of cleaving protein fusions at
      sites adjacent to Lys-Arg.

PMID- 14636708
TI  - High yield production of salidroside in the suspension culture of Rhodiola
      sachalinensis.
AB  - Salidroside has been identified as the most potent ingredient of the Chinese
      medicine herb, Rhodiola sachalinensis. Since the natural supply of this herb is
      rapidly decreasing, we established a compact callus aggregate (CCA) strain and
      culturing system for high yield salidroside production. Several callus strains
      induced from the explants originated from root, stem, leaf and cotyledon of R.
      sachalinensis were established and screened for rapid growth rate, high
      salidroside content and easy propagation in suspension culture condition. The CCA
      strain was established from a callus strain initiated from the cotyledon. The
      kinetics of dry weight accumulation and cellular salidroside content in various
      culture conditions for the strain was determined. For high salidroside
      production, the optimal inoculum amount was 10% and the optimal concentration for
      6-benzylaminopurine and indole-3-butyric acid added in the liquid medium was 5
      and 2.5 mg l-1, respectively. The acidic culture medium and a faster shaking
      speed favored the salidroside accumulation. The addition of 2,4-D, in the liquid
      MS medium and the utilization of L-tyrosol for chemical feeding enhanced
      salidroside production. Using a proper combination of culture condition and
      treatment, salidroside accumulation could reach 57.72 mg g-1 dry weight, that was
      5-10-fold higher than that detected in field-grown plants. The corresponding
      salidroside yield was 555.13 mg l-1, a level suitable for cost effective
      commercial production to compensate the natural resource shortage of R.
      sachalinensis.

PMID- 14636709
TI  - Methanol production is enhanced by expression of an Aspergillus niger pectin
      methylesterase in tobacco cells.
AB  - Tobacco suspension culture cell (Nicotiana tabacum, BY2) was transformed with an
      Aspergillus niger pectin methylesterase (PME; EC 3.1.1.11) cDNA under the control
      of cauliflower mosaic virus (CaMV) 35S promoter. The transformant indicated a
      significant rise of PME and the level of methanol in the transformant increased
      by 28.7% compared to the vector control transformant. This is the first report of
      methanol overproduction in plant cells by means of genetic engineering.

PMID- 14636710
TI  - Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric
      balance.
AB  - A macrokinetic model for Pichia pastoris expressing recombinant human serum
      albumin is proposed. The model describes the balances of some key metabolites,
      ATP and NADH, during glycerol and methanol metabolism. In the glycerol growth
      phase, the metabolic pathways mainly include phosphorylation, glycolysis,
      tricarboxylic acid cycle, and respiratory chain. In the methanol growth phase,
      methanol is oxidized to formaldehyde at first. Then, while a part of formaldehyde
      is oxidized to formate, the rest is condensed with xylulose-5-monophosphate to
      form glyceraldehyde-3-phosphate, and further assimilated to form cell
      constituents. The metabolic pathways following glyceraldehyde-3-phosphate were
      assumed to be similar to those in the glycerol growth phase. Based on the model,
      the macrokinetic bioreaction rates such as the specific substrate consumption
      rate, the specific growth rate, the specific acetyl-CoA formation rate as well as
      the specific oxygen uptake rate are obtained. The specific substrate consumption
      rate and the specific growth rate are then coupled into a bioreactor model such
      that the relationship between substrate feeding rates and the main state
      variables, i.e., the medium volume, the concentrations of the biomass, the
      substrate, and the product, is set up. Experimental results demonstrate that the
      model can describe the cell growth and the protein production with reasonable
      accuracy.

PMID- 14636711
TI  - Stable expression of recombinant human alpha3/4 fucosyltransferase III in
      Spodoptera frugiperda Sf9 cells.
AB  - Human alpha3/4 fucosyltransferase III (FT3; EC 2.4.1.65) synthesizes fucosylated
      glycoconjugates, namely the Lewis (Le) determinants. FT3 is detected in milk,
      gastric mucosa, kidney and other organs, but is found in very low amounts in
      these native tissues. In this work, we describe the expression of a soluble
      secretory form of FT3 (SFT3) in Spodoptera frugiperda (Sf9) insect cells using a
      non-lytic vector system. The coding sequence was cloned into the expression
      vector pIB/V5-His-TOPO which contains the transcriptional control of the Orgyia
      pseudotsugata multicapsid nucleopolyhedrosis virus immediate-early 2 (OpIE2)
      promoter. Transfected cells were selected using blasticidin-HCl. It was observed
      that the secreted activity SFT3 increased until the sixth day of culture when it
      reached the value 1.9 mU x 10(-6) cells and 13.4 mg/l, whereas only 5% of
      activity was retained inside the cells. Western blot analysis of secreted and
      intracellularly retained SFT3 had a similar variation. Comparison of the stable
      with the lytic baculovirus expression system showed that the former yielded
      approx. 13-fold more active SFT3, which was possibly due to a lower accumulation
      of intracellular SFT3.

PMID- 14636712
TI  - A novel granular sludge sequencing batch reactor for removal of organic and
      nitrogen from wastewater.
AB  - Microbial granules were developed at different substrate N/COD ratios in
      sequencing batch reactors (SBR). Results showed that heterotrophic, nitrifying,
      and denitrifying populations could peacefully co-exist in microbial granules,
      while increased substrate N/COD ratio led to significant shifts among three
      populations in granules. Enhanced activities of nitrifying and denitrifying
      populations were obtained in microbial granules developed at high substrate N/COD
      ratios, however, heterotrophic populations in granules tended to decrease with
      the increase of substrate N/COD ratio. It was found that dissolved oxygen (DO)
      concentration had a pronounced effect on the efficiency of denitrification by
      microbial granules, meanwhile the results also indicated that a certain mixing
      power would be provided to ensure mass transfer between liquid and granules
      during denitrification. It was demonstrated that complete organics and nitrogen
      removal can be achieved in single granule-based SBR with high efficiency and
      stable performance. This is the first study to show the capability of microbial
      granules in simultaneous removal of organic carbon and nitrogen from wastewater.

PMID- 14636713
TI  - Biochip as a potential platform of serological interferon alpha2b antibody assay.
AB  - The formation of antibodies against cytokines may play a major role in the
      generation of the immune response and may affect treatment protocols with
      recombinant cytokines. Interferon (IFN) is one of the effective therapeutic
      agents with anti-viral and anti-tumor specific effects. The appearance of IFN
      antibodies in patients may limit the natural and the therapeutic effect by IFNs.
      In contrast to conventional ELISA techniques, we here report a simple biochip
      methodology that enables identification of antibodies against cytokines and
      peptides. The method takes advantage of a functionalized self-assembled monolayer
      modified by N-hydroxysuccinimide (NHS). To validate this surface, four human
      proteins: IFNalpha2b, leptin, growth hormone and human IgG, with molecular sizes
      ranging between 14 and 150 kDa, were used. A number of other parameters for
      protein assay conditions by array technology were evaluated concomitantly.
      Finally, 56 serum samples from patients treated with recombinant human IFNalpha2b
      were simultaneously tested on single chip. In these patients, 16.1% (9 of 56
      cases) were positive for IFNalpha2b antibodies. All results were confirmed in an
      ELISA, specific for the identification of IFNalpha specific antibodies in human
      samples. The potential application of this protein biochip can be amplified
      rapidly and reliably to test not only IFNalpha2b, but also other cytokine
      specific antibodies. The clinical relevance of such assays for investigations in
      autoimmune disorders is expected.

PMID- 14636714
TI  - Degumming of silk fabric with several proteases.
AB  - A crepe silk fabric was treated with different alkaline (3374-L, GC 897-H),
      neutral (3273-C), and acid (EC 3.4 23.18) proteases with the aim to study their
      effectiveness as degumming agents. Proteases were used under optimum conditions
      of pH and temperature, while enzyme dosage (0.05-2 U/g fabric) and treatment time
      (5-240 min) were changed in order to study the kinetics of sericin removal.
      Degumming loss with soap and alkali was 27 wt.%. The maximum amount of sericin
      removed in 1 h was 17.6, 24, and 19 wt.% for 3374-L (2 U/g fabric), GC 897-H
      (1U/g fabric), and 3273-C (0.1 U/g fabric), respectively. Under the experimental
      conditions adopted, EC 3.4 23.18 was almost ineffective as a degumming agent.
      Degumming loss increased as a function of the treatment time, reaching a value of
      25 wt.% with 1 U/g fabric of 3374-L. The morphological analysis showed that
      sericin was completely removed from the warp yarns of the crepe fabric, while the
      highly twisted weft yarns still exhibited the presence of sericin deposits within
      the most internal parts of the close fibre texture. The chromatographic pattern
      of soluble sericin peptides changed as a function of the kind of enzyme used,
      enzyme dosage, and treatment time. A mixture of peptides from 5 to 20 kDa in
      weight, with a weight-average molecular weight of about 12 kDa was obtained.

PMID- 14636716
TI  - Permeation enhancing polymers in oral delivery of hydrophilic macromolecules:
      thiomer/GSH systems.
AB  - Thiolated polymers (= thiomers) in combination with reduced glutathione (GSH)
      were shown to improve the uptake of hydrophilic macromolecules from the GI tract.
      The mechanism responsible for this permeation enhancing effect seems to be based
      on the thiol groups of the polymer. These groups inhibit protein tyrosine
      phosphatase, being involved in the closing process of tight junctions, via a GSH
      mediated mechanism. The strong permeation enhancing effect of various thiomer/GSH
      systems such as poly(acrylic acid)-cysteine/GSH or chitosan-4-thio-butylamidine
      (chitosan-TBA)/GSH could be shown via permeation studies on freshly excised
      intestinal mucosa in Ussing-type chambers. Furthermore, the efficacy of the
      system was also shown in vivo. By utilizing poly(acrylic acid)-cysteine/GSH as
      carrier matrix, an absolute oral bioavailability for low molecular weight heparin
      of 19.9 +/- 9.3% and a pharmacological efficacy--calculated on the basis of the
      areas under the reduction in serum glucose levels of the oral formulation versus
      subcutaneous (s.c.) injection-for orally given insulin of 7% could be achieved.
      The incorporation of salmon calcitonin in chitosan-TBA/GSH led on the other hand
      to a pharmacological efficacy based on the areas under the reduction in plasma
      calcium levels of the oral thiomer formulation versus intravenous (i.v.)
      injection of 1.3%. Because of this high efficacy (i), the possibility to combine
      thiomer/GSH systems with additional low molecular weight permeation enhancers
      acting in other ways (ii) and minimal toxicological risks as these polymers are
      not absorbed from the GI tract (iii), thiolated polymers represent a promising
      novel tool for the oral administration of hydrophilic macromolecules.

PMID- 14636717
TI  - A new pH-responsive and glutathione-reactive, endosomal membrane-disruptive
      polymeric carrier for intracellular delivery of biomolecular drugs.
AB  - In this study, we have designed, synthesized and characterized a novel pH
      responsive polymeric carrier for the enhanced cytoplasmic delivery of enzyme
      susceptible drugs, such as antisense oligonucleotides, proteins and peptides. A
      novel functionalized monomer, pyridyl disulfide acrylate, was synthesized and
      incorporated into an amphiphilic copolymer consisting of methacrylic acid and
      butyl acrylate, which resulted in a glutathione- and pH-sensitive, membrane
      disruptive terpolymer with functional groups, that allow thiol-containing
      molecules to be readily conjugated. Conjugation and/or ionic complexation with
      oligopeptides or antisense oligonucleotides were performed and characterized.
      Hemolytic activity at low pHs remained high even after the
      conjugation/complexation with oligopeptides and asODNs. This polymer showed no
      toxicity, as determined with mouse 3T3 fibroblasts and human THP-1 macrophage
      like cells. Uptake of the radiolabeled polymer and enhanced cytoplasmic delivery
      of FITC-ODN was also studied in THP-1 macrophage-like cells.

PMID- 14636718
TI  - Effects of ethylene glycol-based graft, star-shaped, and dendritic polymers on
      solubilization and controlled release of paclitaxel.
AB  - New methods and pharmaceutical compositions were developed to increase the
      aqueous solubility of paclitaxel (PTX), a poorly water-soluble drug. Graft and
      star-shaped graft polymers consisting of poly(ethylene glycol) (PEG400) graft
      chains increased the PTX solubility in water by three orders of magnitude.
      Polyglycerol dendrimers (dendriPGs) dissolved in water at high concentrations
      without significantly increasing the viscosity and, at 80 wt.%, were found to
      increase the solubility of PTX 10,000-fold. The solubilized PTX was released from
      graft polymers, star-shaped graft polymers, and the dendriPGs into the
      surrounding aqueous solution. The release rate was a function of the star shape
      and the dendrimer generation. The availability of the new graft, star and
      dendritic polymers having ethylene glycol units should permit development of
      novel delivery systems for other poorly water-soluble drugs.

PMID- 14636719
TI  - Modulation of secretory functions in epithelia by adenovirus capsid proteins.
AB  - To evaluate the safety of adenovirus-derived capsid proteins for ocular gene
      delivery, we have investigated their effects on the morphology and function of
      the acinar epithelial cells of the lacrimal gland. These cells are responsible
      for basal and stimulated release of proteins and electrolytes into ocular fluid,
      a process essential in maintaining the health of the ocular surface. Acinar
      epithelial cells from rabbit lacrimal gland were exposed to one of two adenovirus
      serotype 5 capsid proteins, penton or knob (the carboxy-terminal fragment of the
      fiber capsid protein). Sustained (16-18 h) exposure to the penton at 20 microg/ml
      was associated with major changes in the organization of the regulated secretory
      pathway and cytoskeleton. These changes included an apparent loss of mature
      secretory vesicles enriched in rab3D around the apical lumen as well as a
      depletion of apical actin. The microtubule array in penton-treated acini also
      exhibited bundling and disorganization. None of these effects were elicited by
      exposure to knob protein. Penton treatment also caused a significant (p < or =
      0.05) increase and decrease in basal and carbachol-stimulated release,
      respectively, of bulk protein. Competition studies showed that RGD peptide
      partially prevented the penton-induced changes in rab3D-enriched secretory
      vesicles and actin filaments. These findings suggest that the adenovirus penton
      protein compromises normal acinar secretory compartment organization and function
      and that these changes are due at least partly to penton-integrin interactions.

PMID- 14636720
TI  - Polyion complex micelles entrapping cationic dendrimer porphyrin: effective
      photosensitizer for photodynamic therapy of cancer.
AB  - Photosensitizers play a crucial role in the photodynamic therapy (PDT) of cancer.
      In this study, a third-generation aryl ether dendrimer porphyrin with 32 primary
      amine groups on the periphery, [NH2CH2CH2NHCO]32DPZn, and pH-sensitive, polyion
      complex micelles (PIC) composed of the porphyrin dendrimer and PEG-b
      poly(aspartic acid), were evaluated as new photosensitizers (PSs) for PDT in the
      Lewis Lung Carcinoma (LLC) cell line. The preliminary photophysical
      characteristics of [NH2CH2CH2NHCO]32DPZn and the corresponding micelles were
      investigated. Electrostatic assembly resulted in a red-shift of the Soret peak of
      the porphyrin core and the enhanced fluorescence. Compared to the dendrimer
      porphyrin [NH2CH2CH2NHCO]32DPZn, relatively low cellular uptake of dendrimer
      porphyrin [NH2CH2CH2NHCO]32DPZn incorporated in the PIC micelle was observed, yet
      the latter exhibited enhanced photodynamic efficacy on the LLC cell line.
      Importantly, the use of PIC micelles as a delivery system reduced the dark
      toxicity of the cationic dendrimer porphyrin, probably due to the biocompatible
      PEG shell of the micelles.

PMID- 14636721
TI  - Drug delivery to resistant tumors: the potential of poly(alkyl cyanoacrylate)
      nanoparticles.
AB  - Simultaneous cellular resistance to multiple lipophilic drugs represents a major
      problem in cancer chemotherapy. This drug resistance may appear clinically either
      as a lack of tumor size reduction or as the occurrence of clinical relapse after
      an initial positive response to antitumor treatment. The resistance mechanism can
      have different origins either directly linked to specific mechanisms developed by
      the tumor tissue or connected to the more general problem of distribution of a
      drug towards its targeted tissue. The purpose of this paper is to summarize the
      results of the use of poly(alkyl cyanoacrylate) nanoparticles to overcome
      multidrug resistance (MDR) phenomena at both the cellular and the non-cellular
      level.

PMID- 14636722
TI  - A new process for making reservoir-type microcapsules using ink-jet technology
      and interfacial phase separation.
AB  - A new microencapsulation technique that utilizes interfacial mass transfer
      between two mutually soluble liquids has been developed. The technique is based
      on formation of a solid polymer film at the interface of a solution of a water
      insoluble polymer and an aqueous solution, resulting from the mutual mass
      transfer of solvents (i.e., solvent exchange). Reservoir-type microcapsules were
      prepared by inducing this phenomenon to occur on the surface of an aqueous
      droplet. One method of implementation employed a dual microdispenser system that
      consisted of two ink-jet nozzles. The nozzles, producing droplets of a polymer
      solution and an aqueous drug solution, respectively, were aligned to allow
      collision of pairs of the droplets. The collision resulted in spreading of the
      polymer solution on the aqueous droplet and simultaneous solvent exchange, to
      form a polymeric membrane around the aqueous droplet. The formation of the
      polymer membrane depended largely on the favorable spreading of the polymer
      solution on the aqueous droplets and fast solvent exchange, and required
      judicious selection of the organic solvent. Simple and fast screening methods
      were developed for selection of a proper solvent. Ethyl acetate was chosen as one
      of the most desirable solvents through the screening procedures. Ethyl acetate
      and the dual microdispenser system were used to form microcapsules that were
      subsequently examined by microscopic methods to demonstrate their unique
      geometry.

PMID- 14636724
TI  - A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG
      hybrid conjugate micelles.
AB  - The conjugate of antisense c-raf oligonucleotide (ODN) and poly(ethylene glycol)
      (PEG) was synthesized for intracellular ODN delivery. When combined with
      polyethylenimine (PEI), the ODN-PEG conjugate self-associated to form
      polyelectrolyte complex micelles in aqueous solution. The effective hydrodynamic
      diameter of the micelles was ca. 70 nm with a narrow size distribution. Flow
      cytometry analysis indicated that the cellular uptake of the micelles by A2780
      cells was much higher than that of ODN alone. The micelles also showed a superior
      antiproliferative activity against ovarian cancer cells in vitro and in vivo.

PMID- 14636723
TI  - Effect of Terplex/VEGF-165 gene therapy on left ventricular function and
      structure following myocardial infarction. VEGF gene therapy for myocardial
      infarction.
AB  - BACKGROUND: We used a novel lipopolymeric gene delivery system, TeplexDNA, to
      transfect myocardium with plasmid vascular endothelial growth factor-165 (pVEGF)
      and evaluated the ability of pVEGF to preserve left ventricular function and
      structure after coronary ligation in a rabbit model. METHODS: New Zealand white
      rabbits underwent circumflex coronary ligation after direct intramyocardial
      injection of either Terplex alone or Terplex + 50 microg pVEGF-165. Serial
      echocardiography and histologic studies were performed (n = 12/group). Mortality
      did not differ between groups. The data is reported as the mean +/- standard
      deviation. RESULTS: Over the 21 days following coronary ligation, pVEGF-165
      treated animals demonstrated significant improvement in fractional shortening (20
      25%, p = 0.02), long axis two-dimensional ejection fraction (42-51%, p=0.02) and
      short axis m-mode ejection fraction (46-54%, p = 0.02). No significant
      improvements were noted in the control group. VEGF-treated animals had a 50%
      increase in peri-infarct vessel density and a trend towards a smaller infarct
      size (20% vs. 29%, p = 0.10). In animals receiving pVEGF-165, the diastolic
      ventricular area increased from 1.87 +/- 0.24 cm2 prior to ligation to 2.19 +/-
      0.23 cm2 at 21 days following ligation, compared to an increase from 1.84 +/-
      0.38 to 2.54 +/- 0.55 cm2 over the same period in control animals (p = 0.03).
      Similarly, the systolic ventricular area in VEGF-165 animals increased from 1.06
      +/- 0.26 cm2 prior to ligation to 1.50 +/- 0.29 cm2 at 21 days following
      ligation, compared to an increase from 1.16 +/- 0.30 to 1.86 +/- 0.43 cm2 over
      the same period in the control animals (p = 0.04). CONCLUSION: TerplexDNA
      mediated delivery of plasmid VEGF administered at the time of coronary occlusion
      improves left ventricular function and reduces left ventricular dilation
      following myocardial infarction.

PMID- 14636725
TI  - In vitro and in vivo gene transfer with poly(amino acid) vesicles.
AB  - Non-viral gene delivery systems utilise either amine lipids or polyamines and
      although non-viral gene delivery systems are said to have a superior safety
      profile to viruses, the polyamines such as poly(L-lysine) are toxic when used
      without derivatisation and usually require specific receptor mediated uptake
      and/or endosomolytic agents to be effective. However, the conversion of poly(L
      lysine) and poly(L-ornithine) polyamino acids into amphiphilic vesicle forming
      polymers reduces the toxicity of the polyamino acids and enables the resulting
      polyamino acid vesicles to deliver genes both in vitro and in vivo in the absence
      of receptor specific ligands and endosomolytic agents. The incorporation of a
      distearoylphosphatidylethanolamine poly(ethylene glycol)-galactosamine conjugate
      (with the galactosamine unit at the distal end of the poly(ethylene glycol)
      moiety) into the polyamino acid formulations improved in vitro gene transfer in
      the case of the amphiphilic poly(L-ornithine) (POP) although no in vivo targeting
      was detected with the galactosamine formulations. We conclude that the conversion
      of poly(L-lysine) and poly(L-ornithine) into amphiphilic colloid forming
      molecules reduces their toxicity, thus allowing these systems to be used for gene
      transfer in vivo. It is possible that this approach may be extended to other
      polyamines.

PMID- 14636726
TI  - Extracellular and intracellular barriers in non-viral gene delivery.
AB  - Complexes of DNA with cationic lipids and cationic polymers are frequently used
      for gene transfer. Extracellular interactions of the complexes with anionic
      glycosaminoglycans (GAGs) may interfere with gene transfer. Interactions of GAGs
      with carrier DNA complexes have been studied using tests for DNA relaxation
      (ethidium bromide intercalation), DNA release (electrophoresis), and transfection
      (pCMVbGal transfer into RAA smooth muscle cells). Several cationic lipid
      formulations (DOTAP, DOTAP/Chol, DOTAP/DOPE, DOTMA/DOPE, DOGS) and cationic
      polymers (fractured dendrimer, polyethylene imines 25 and 800 kDa, polylysines 20
      and 200 kDa) were tested. Polycations condensed DNA more effectively than
      monovalent lipids. Hyaluronic acid did not release or relax DNA in any complex,
      but it inhibited transfection by some polyvalent systems (PEI, dendrimers, DOGS).
      Gene transfer by other carriers was not affected by hyaluronic acid. Sulfated
      GAGs (heparan sulfate, chondroitin sulfates B and C) completely blocked
      transfection, except in the case of liposomes with DOPE. Sulfated GAGs relaxed
      and released DNA from some complexes, but these events were not prerequisites for
      the inhibition of transfection. Furthermore, preliminary results suggest that
      cell surface GAGs, particularly heparan sulfate, inhibit gene transfer by
      cationic lipids and polymers.

PMID- 14636727
TI  - Biochemical characterization of individual injury pattern and injury severity.
AB  - BACKGROUND: Estimation of trauma severity currently relies on clinical diagnoses
      and scoring systems. However, the early estimation of the severity of chest
      trauma and overall soft tissue trauma (STT) remains insufficient. Traditional
      trauma scoring systems fail to reflect the individual trauma pattern and
      severity, neglecting the different outcomes after injuries in different body
      regions. Therefore, the aim of this prospective study was to detect laboratory
      markers that may reflect the pattern and extent of individual trauma in the very
      early phase after injury. PATIENTS AND METHODS: In 107 non-selected trauma
      patients, blood samples were collected almost immediately and then at short
      intervals after the trauma. In addition to the biochemical analysis of 20
      different mediators viewed as potential trauma markers, the following data were
      correlated with the laboratory results: injury severity score (ISS), polytrauma
      score (PTS), Ulmer score HTAPE (trauma pattern specific: head (H), thorax (T),
      abdomen (A), pelvis (P), extremities (E); 0-3 degrees each), multiple organ
      failure score (MOF), overall, primary and secondary lethality. RESULTS: ISS and
      the severity of head injury were clearly higher in non-survivors (n=17) than in
      survivors (n=90) (median ISS: 35 versus 18; median severity of head injury (H): 3
      versus 1). Whereas head injury was correlated with early death (<or=3 days:
      r=0.45), late death (>3 days post-trauma) was influenced by thoracic trauma
      (r=0.15) as well as by soft tissue trauma (STT, r=0.12). Of all investigated
      mediators, interleukin-6 (IL-6) displayed the highest correlations (r=0.66,
      P<0.00001) with the extent of chest trauma, followed by correlations with PTS,
      STT, fracture trauma (FT) and ISS during the first hour after trauma. There was
      no correlation between IL-6 and head injury. The extent of STT was correlated
      best to IL-8 (r=0.75), IL-6 (r=0.54), and creatine kinase (CK, r=0.49) plasma
      concentrations. CONCLUSION: In the very early stage after an accident the
      severity of chest trauma is strongly correlated with the plasma concentration of
      IL-6, and the extent of overall soft tissue trauma (STT) to plasma concentrations
      of IL-8, IL-6, and CK.

PMID- 14636728
TI  - Complex fractures, do we operate on enough to gain and maintain experience?
AB  - Complex fractures are generally assumed by our profession to require adequate
      training and continuing practice to treat optimally. The quantity of complex
      fractures treated in individual hospitals and by or under the care of individual
      orthopaedic consultants may have implications regarding the quality of care for
      particular patients and also for the training of specialist registrars.A complex
      fracture was defined as a comminuted peri- or intra-articular fracture or
      segmental shaft fracture: fractures acknowledged at specialist fracture courses
      and by special trauma surgeons to require particular training and experience to
      treat optimally. The AO classification was used: most fractures were in AO groups
      B and C [M.E. Muller, S. Narazian, P. Koch, J. Schatzker, The Comprehensive
      Classification of Longbones, Springer, Berlin, 1990]. Theatre records were used
      to identify all operated orthopaedic trauma cases over a period of 1 year in one
      District General Hospital (DGH) and one University Hospital, each serving
      populations of over 300000 and for 6 months in one DGH (population approximately
      300000). Radiographs and hospital records were reviewed by two orthopaedic
      surgeons and the number and type of complex fractures documented as defined
      above. In hospital A, 69 complex fracture operations were carried out under the
      care of six consultants in 12 months. In hospital B, 24 complex fractures were
      treated by five consultants over a 6-month period and in hospital C, 127 complex
      fractures were treated by 10 consultants over a 12-month period. Some consultants
      (different consultants for different fracture regions) did not operate on any
      complex fracture of the proximal, mid, or distal humerus; proximal, mid, or
      distal radius or ulna; proximal, mid, or distal femur; proximal, mid, or distal
      tibia; calcaneum; peri-prosthetic; Lisfranc; or talus fracture during the
      specific time period. Some consultants only treated one or two such fractures.
      Where two surgeons had developed an area of special interest and cross-referral
      were encouraged individual surgeons were operating on up to 25 complex cases in
      their area of interest.This audit has shown that individual complex fractures
      present infrequently to particular hospitals and surgeons. This finding raises
      questions about the optimal management of such fractures: are we maintaining a
      sufficient level of expertise, or should there be more cross-referrals to
      surgeons with a specific interest either in trauma or in a particular anatomical
      region?

PMID- 14636729
TI  - Deaths associated with snow skiing in Colorado 1980-1981 to 2000-2001 ski
      seasons.
AB  - OBJECTIVES: To investigate the trend and injury patterns of deaths associated
      with snow skiing in Colorado between 1980 and 2001. METHODS: Death certificates
      were searched electronically and reviewed manually. Total skier ticket sales were
      used to calculate death rates. Types of injuries and characteristics of those who
      died were investigated. RESULTS: A total of 274 skier deaths occurred between
      1980 and 2001 in Colorado. Death rates ranged from 0.53 to 1.88 per million skier
      visits. The majority of deaths were among males (>81%). Ages ranged from 7 to 77
      years with an average of 32 years. The greatest number of deaths associated with
      downhill skiing (76 deaths) occurred between 10:00 a.m. and 2:00 p.m. while the
      greatest number of deaths associated with cross-country skiing happened between
      2:00 and 6:00 p.m. About 65% of deaths associated with downhill skiing (133
      cases) died of traumatic injuries resulting from collisions. CONCLUSIONS: A
      slight increase in the rate of ski-related deaths was observed. The role of
      collisions in ski-related deaths warrants further investigation to reduce the
      risk of this activity for all skiers. Further work is needed to determine the
      efficacy of helmet use to reduce the risk of head injuries in the skiing
      population.

PMID- 14636730
TI  - Factors affecting the severity of horse-related injuries.
AB  - Horse riding and handling are uniquely dangerous. Knowledge of the risk factors
      of horse-related injuries is essential to prevent them. We aimed to define the
      factors that affect the severity of horse-related injuries and the length of
      hospital stay. A number of 231 patients (136 females and 95 males) with horse
      related injuries were studied. A generalized linear model was used to test the
      effect of age, sex, cause of injury, complexity of the mechanism of injury, year,
      place of injury and profession of the injured, on the injury severity score (ISS)
      and the hospital stay. Fall from a horse was the most common cause of injury
      (67%). Most of the patients were non-professional (153, 66%). Females were
      significantly younger than males (P<0.001, t-test). Statistical analysis showed
      that the primary mechanism of injury (F=2.73, P=0.014) and the complexity of this
      mechanism (F=4.47, P=0.013) significantly affected the duration of hospital stay.
      None of the studied variables affected the injury severity score. The mechanism
      of the horse-related injuries and their complexity significantly affected the
      duration of hospital stay but not the injury severity score.

PMID- 14636731
TI  - Complications with use of the Epistat in the arrest of midfacial haemorrhage.
AB  - Control of midfacial haemorrhage can be difficult, especially in the multiply
      injured patient, either at the scene of injury, or in the Accident and Emergency
      Department. The use of Epistats has proven invaluable in this setting. Potential
      problems exist with their use and this is illustrated with examples, together
      with strategies for overcoming them. A summary of the didactic method of safe use
      of this life saving technique is insert the Epistat, aiming for a fingertip
      placed at the soft palate;inflate the posterior cuff;withdraw the Epistat
      slightly, to position the posterior cuff within the nasal choanae;inflate the
      anterior (intranasal) cuff.

PMID- 14636732
TI  - When can patients blow their nose and fly after treatment for fractures of
      zygomatic complex: the need for a consensus.
AB  - PURPOSE: To determine current professional advice to patients about refraining
      from nose blowing and air travel following treatment of zygomatic fractures.
      METHODS: A postal questionnaire was sent to 261 consultant oral and maxillofacial
      surgeons (OMFS) in the UK. They were asked about advice given to patients
      regarding length of time to refrain from nose blowing and air travel following
      treatment of zygomatic fractures. RESULTS: A total of 184 (71%) replies were
      received. Advice regarding the length of time to refrain from nose blowing and
      air travel ranged from no advice to 8 weeks. About 90% of respondents based their
      advice on common sense and traditional practice. CONCLUSIONS: Advice given to the
      patients following the treatment of zygomatic fractures varies widely. Most
      consultants based their advice on traditional practice and common sense. In the
      absence of widely accepted guidelines, there is a need for an agreement among
      clinicians on advice given to the patients.

PMID- 14636733
TI  - Is spinal immobilisation necessary for all patients sustaining isolated
      penetrating trauma?
AB  - INTRODUCTION: Previous work suggests that patients with isolated penetrating
      trauma rarely require spinal immobilisation. This study aimed to identify the
      incidence of mechanically unstable, or potentially mechanically unstable, spinal
      column injuries in penetrating trauma patients. The study also aimed to identify
      the incidence of spinal cord injury as a result of penetrating trauma in
      Scotland. DESIGN: Retrospective analysis of prospectively collected data from the
      Scottish Trauma Audit Group (STAG). METHODS: Study patients were identified from
      the period 1992-1999. Patients coded for both penetrating trauma and spinal
      column or spinal cord injury were included. Case records, theatre notes and post
      mortem information were also examined. RESULTS: 34903 patients were available for
      study. Twenty-seven patients were coded as having had penetrating trauma and
      concurrent spinal injury. 15 were excluded as they also had a major blunt
      mechanism of injury or had no actual injury to the spinal cord or column. In the
      remaining 12 patients, four cervical, one combined cervical and thoracic and
      seven thoracic spinal cord injuries were identified. 11 were male and 11 were
      assaulted. One assault was due to a gunshot wound; 10 resulted from sharp
      weapons. Four complete cord transections and nine partial cord lesions were
      identified. All 12 patients with spinal cord injury associated with isolated
      penetrating trauma either had obvious clinical evidence of a spinal cord injury
      on initial assessment or were in traumatic cardiac arrest. All had spinal
      immobilisation. CONCLUSION: Fully conscious patients (GCS=15) with isolated
      penetrating trauma and no neurological deficit do not require spinal
      immobilisation.

PMID- 14636734
TI  - Stress fractures of the lumbar pars interarticularis in athletes: a review based
      on long-term results of 18 professional cricketers.
AB  - The physical demand of the modern game of cricket on the fast bowler is known to
      cause stress fractures of the lumbar spine. Between 1983 and 2001, we diagnosed
      pars interarticularis defects in 18 professional cricketers contracted to a
      single English County Cricket Club. Eight of these players were treated
      conservatively, with rest, supervised rehabilitation, bowling action analysis and
      re-education where necessary. The remaining 10 were treated operatively, 9 by
      Buck's repair of the spondylolytic lesion. All 18 players returned to
      professional sport.We recommend treatment of this select group of sportsmen in a
      unit consisting of a specialist physiotherapist, a bowling coach and a spinal
      surgeon. Should conservative measures fail, we recommend Buck's repair as the
      operation of choice.

PMID- 14636735
TI  - Flexion-distraction injury of the thoracolumbar spine.
AB  - Flexion-distraction injury of the thoracolumbar spine results from a failure of
      both the posterior and middle columns under tension, and this injury is uncommon.
      Progressive kyphotic deformity frequently develops after conservative treatments.
      We report our 10 years' experience with the surgical treatment of flexion
      distraction injuries. From January 1991 to December 2000, 30 flexion-distraction
      thoracolumbar spinal injuries were treated at our hospital. We included 23
      patients in this study, and seven patients were excluded. The mean age of the
      patients was 37.2 years. Six were female and 17 were male. All patients received
      open reduction, posterior instrumentation, and posterior fusion at the level of
      injury. Post-operatively, patients were all placed in total contact orthoses for
      3 months. Ambulation was allowed immediately after brace application.The mean
      follow-up period was 84.7 months follow-up. The final average follow-up kyphotic
      angulation was 5.4 degrees, which is an average improvement of 9.5 degrees. Post
      operative back pain ratings indicated that result of surgery was mostly good, and
      the neurological evaluation was almost normal after long-term follow-up. A
      satisfactory reduction and good stabilisation with solid fusion was achieved in
      all cases, without any significant loss of reduction. Surgical treatment of
      reduction and stabilisation with posterior instrumentation and fusion is
      suggested in patients with flexion-distraction injury of the thoracolumbar spine.

PMID- 14636736
TI  - Traumatic sternal fracture: outcome following admission to a Thoracic Surgical
      Unit.
AB  - INTRODUCTION: We reviewed our experience of the in-hospital management and early
      follow-up of patients admitted with a traumatic sternal fracture to a Thoracic
      Surgical Unit. PATIENTS AND METHODS: Over a 7-year period, 73 consecutive
      patients (51 males) with a median age of 51 (range 17-84) years were admitted
      through the Emergency Department with an acute traumatic sternal fracture. The
      patients were hospitalised for cardiorespiratory monitoring, pain control and
      physiotherapy. Outpatient follow-up occurred 6 weeks after discharge. RESULTS:
      The median hospital stay was 2 days (range 1-15 days). Sixty-four patients (88%)
      did not require parenteral analgesia or any other procedure that would
      necessitate admission to hospital. Three patients (4%) with severely displaced
      fractures and complex co-morbidities required surgical correction. Follow-up
      revealed no significant complications. CONCLUSIONS: Admission to hospital is not
      necessary for every patient sustaining a sternal fracture and should be reserved
      for those with high-impact trauma, severely displaced fractures, significant
      associated injuries, complex analgesic requirements, important co-morbidities or
      inadequate domestic support.

PMID- 14636737
TI  - Soft tissue problems in ankle fractures treated surgically. A prospective study
      of 154 consecutive closed ankle fractures.
AB  - We performed a prospective registration of primary soft tissue injuries and
      perioperative soft tissue complications the first 3 months after surgery in ankle
      fractures treated by open reduction and internal fixation. Open fractures and
      polytraumatized patients were excluded. The 154 consecutive patients (90 women)
      with an average age of 54.5 (S.D. 18.3) years were registered. Primary soft
      tissue injuries according to Tscherne's classification were noted in 22 patients
      (14.2%). Major perioperative soft tissue complications requiring revision
      occurred in five patients (3.2%). Minor perioperative soft tissue complications
      treated non-operatively occurred in 29 patients (18.8%). A significantly higher
      incidence of perioperative soft tissue complications occurred in alcohol abusers
      (P=0.043), after high-energy trauma (P=0.043), and after primary soft tissue
      injuries (P=0.004). Other possible risk factors such as age, gender, fracture
      type, diabetes, arteriosclerosis, coronary heart disease, and hypothyroidism had
      no statistically significant influence on the incidence of perioperative soft
      tissue complications.

PMID- 14636738
TI  - An outcomes assessment of intra-articular calcaneal fractures, using patient and
      physician's assessment profiles.
AB  - Thirty-six patients with intra-articular displaced calcaneal fractures were
      examined to determine both physician- and patient-based outcomes. Three groups
      were selected. Group A was treated with open reduction and internal fixation,
      group B was treated with open reduction internal fixation and supplemental bone
      graft augmentation and the patients in group C were treated with plaster cast
      immobilisation and no formal operative treatment. All cohorts were well matched
      for age, sex and severity of injury. Patients were evaluated using both the
      American Foot and Ankle Society Scoring System (AFASS) and the short form 36 (SF
      36). Minimum time to follow up was 4 years. No significant difference was
      observed between the three groups with regards to pain and functional outcomes
      using the AFASS score (P>0.05). No difference was observed between the three
      groups using the SF-36 score (P>0.1). A statistically significant difference was
      observed, using radiological criteria, between both groups A and B when compared
      to the non-operative group C. The rate of wound infection in groups A and B was
      31.5%. No correlation was found between the SF-36 score and the AFASS score. No
      correlation was found between the radiological score and either the SF-36 or the
      AFASS score. This study has found that the conservative treatment of calcaneal
      fractures can produce satisfactory outcomes with lower morbidity than surgically
      treated fractures.

PMID- 14636739
TI  - Blunt laryngotracheal injury following accidental strangulation.

PMID- 14636740
TI  - Fractures of the thoracolumbar vertebrae from sledging: a recurrent British
      winter problem.

PMID- 14636741
TI  - Thoracic fracture dislocations without vertebral clinical signs.

PMID- 14636742
TI  - Symptomatic heterotopic pancreas following seat belt injury.

PMID- 14636744
TI  - Spinal accessory nerve palsy following blunt trauma.

PMID- 14636743
TI  - Storm in a T-CUP: thyroid crisis following trauma.

PMID- 14636745
TI  - Penetrating head injury from an electrical plug.

PMID- 14636746
TI  - Skin edge debridement made easy.
AB  - A simple technique to obtain more linear skin edges during wound edge
      debridement, using a dissecting forceps and scalpel, is presented.

PMID- 14636747
TI  - A new specifically designed forceps for chest drain insertion.
AB  - Insertion of a chest drain can be associated with serious complications. It is
      recommended that the drain is inserted with blunt dissection through the chest
      wall but there is no specific instrument to aid this task. We describe a new
      reusable forceps that has been designed specifically to facilitate the insertion
      of chest drains.A feasibility study of its use in patients who required a chest
      drain as part of elective cardiothoracic operations was undertaken. The primary
      end-point was successful and accurate placement of the drain. The operators also
      completed a questionnaire rating defined aspects of the procedure. The new
      instrument was used to insert the chest drain in 30 patients (19 male, 11 female;
      median age 61.5 years (range 16-81 years)). The drain was inserted successfully
      without the trocar in all cases and there were no complications. Use of the
      instrument rated as significantly easier relative to experience of previous
      techniques in all specified aspects. The new device can be used to insert
      intercostal chest drains safely and efficiently without using the trocar or any
      other instrument.

PMID- 14636748
TI  - If it can't be measured it can't be managed. The paucity of outcome measures in
      burn care.

PMID- 14636749
TI  - Evaluation of donor skin viability: fresh and cryopreserved skin using
      tetrazolioum salt assay.
AB  - Cell viability assessment in allograft skin is an essential step to ensure a
      supply of good quality allograft skin for clinical repair of wounds. It is widely
      recognised that 'take' of allografts is strongly influenced grafted by tissue
      viability. The aim of this study was to set-up storage protocols that maintain
      high viability of the allograft after harvest, treatment and storage. In this
      study, the viability of post-mortem allografts (n=350) harvested from 35
      different donors, was investigated using the MTT salt assay. The conditions of
      preparation and storage of the allograft included: 1. Fresh skin samples (about
      12, 30, and 60h after harvesting). 2. The same specimens (stored at 4 and 37
      degrees C) tested for at least 1 month. 3. Samples after cryopreservation and
      thawing. 4. Thawed specimens tested daily for at least 6 days. Parallel
      histomorphological analysis performed, under each of these conditions, showed a
      correlation between changes in structure and changes in viability as measured by
      the MTT quantitative assay. The viability index (VI) of skin is expressed as the
      ratio between the optical density (O.D.) produced in the MTT assay by the skin
      sample and its weight in grams. The percentage viability index is the ratio of
      the VI of the fresh sample (considered as 100% viability) and the value of
      specimens from the same harvest batch after storage or cryopreservation. The
      results indicated that samples tested within 12-30h from harvesting have an
      average viability index of about 75 with little variation. Samples tested within
      60h have an average viability index of 40, showing a viability decrease of about
      50%. A protocol to treat skin within a maximum of 30h was, therefore, set-up. The
      data suggested that skin stored at 37 degrees C, undergoes a viability increase
      during the first 2 days after harvesting. However, the viability under these
      conditions then decreased very quickly. After 6 days of preservation at this
      temperature the samples were no longer viable (PVI = 0). The tissue structure
      started to become damaged after 3 days. On the other hand, skin stored at 4
      degrees C, showed a very slow viability decrease. After 15 days, viability was
      still almost 25% of the fresh sample. The tissue architecture showed no signs of
      damage under these conditions until day 7 from harvesting. MTT analysis was
      performed on the specimens cryopreserved with DMSO at 10%. These measurements
      were compared to viability assessment of the same fresh skin samples (considered
      as 100%) that were analysed within 30h from harvesting. The average PVI of thawed
      skin was 54% of the fresh sample. This result demonstrates that the viability of
      cryopreserved skin is comparable to the viability of fresh skin stored at 4
      degrees C for 4 days. The PVI of thawed skin samples decreased dramatically
      within 24h, and had reached 0% within 6 days.

PMID- 14636750
TI  - Role of histamine receptors in the regulation of edema and circulation postburn.
AB  - Despite histamine being a potent endogenous vasoactive agent released in
      increasing amounts postburn, its role in postburn oedema formation has been
      controversial and its effect on burn circulation poorly investigated. The present
      study investigated the involvement of H(1), H(2) and H(3) receptors in postburn
      edema in rats exposed to skin and muscle burns and their influence on skin
      circulation postburn. We used the selective antagonists clemastine (H(1)),
      ranitidine (H(2)), thioperamide (H(3)) and the selective H(3) receptor agonist,
      imetit. Results showed that none of the antagonists or the H(3) agonist had
      significant effect on postburn edema measured by quantitative spectrophotometric
      analysis of extravasated Evans blue-albumin in the full-thickness burned skin or
      muscle. Clemastine and thioperamide failed to induce significant effect on blood
      flow in the partial- or full-thickness skin burn injury as measured by laser
      Doppler flowmetry, while ranitidine significantly (P<0.01) reduced blood flow in
      the full-thickness burn. In contrast, the H(3) receptor agonist, imetit,
      significantly increased blood flow, both in the partial-thickness burn injury
      (P<0.05) and in the full-thickness burn (P<0.01). Moreover, imetit significantly
      (P<0.01) increased mean arterial pressure while thioperamide significantly
      (P<0.01) reduced systemic pressure. In conclusion, H(1), H(2) and H(3) receptors
      are not important actors in the regulation of vascular patency permeability,
      whereas H(3) receptors play an important role by increasing skin circulation
      postburn, presumably by relaxation of vascular smooth muscle and/or by
      interacting with other inflammatory neurotransmitters. Data also suggest that
      H(2) receptor blockers may not be best choice for stress ulcer prophylaxis in
      burn patients.

PMID- 14636751
TI  - Validation of an objective scar pigmentation measurement by using a
      spectrocolorimeter.
AB  - Scar pigmentation changes throughout its maturation process and it is often used
      as one of the indicators for scar maturation, yet it is often rated subjectively.
      The purpose of this study was to investigate the application of a commercial
      spectrocolorimeter to produce a reliable measurement on scar pigmentation.
      Commission Internationale de l'Eclairage (CIE) model of color has been adopted in
      this study for measurement of scar pigmentation 24 patients with hypertrophic
      scars at different stages of maturation were selected for the study, were
      inspected by two therapists using the Vancouver scar scale (VSS) and then using
      spectrocolorimeter for inter-rater reliability. The measurements were taken after
      30min by the same group of therapists (test-retest reliability). Results
      indicated that the inter-rater reliability among the three therapists was
      satisfactory, with intra-class correlation coefficient (ICC) (2, 2) from 0.50 to
      0.99 in all the three color parameters. The test-retest reliability of the
      spectrocolorimeter was satisfactory with ICC (3, 6) ranged from 0.95 to 0.99. A
      significant difference was also noted between the measurements of normal skin and
      hypertrophic scar (P<0.00, t-values: from 2.78 to 0.05, d.f.: from 29.7 to 46.00)
      in all color parameters, except the chroma C(*). We also found a positive
      relationship between VSS scores and the spectrocolorimeter readings. The
      spectrocolorimeter is found to be a reliable instrument to quantify scar
      pigmentation and to differentiate normal skin and scar tissue. With further
      studies, the constructs of scar properties could further be explored using this
      spectrocolorimeter.

PMID- 14636752
TI  - Indocyanine green video angiographies help to identify burns requiring operation.
AB  - The key decision in the treatment of thermal injuries is the determination of the
      depth of the burn wound and the resultant decision on treatment options. The
      trend in the treatment of deep dermal and full thickness burns is toward very
      early excision and grafting to reduce the risk of infection, decrease scar
      formation, shorten hospital stay, and thereby reducing costs. Traditionally, this
      has involved serial clinical examinations, which involves primarily subjective
      judgment. Various objective examination techniques, supplementing the clinical
      diagnosis, have been suggested, but none has yet achieved widespread clinical
      acceptance. It has frequently been postulated that the blood flow in injured
      tissue indicates the extent of tissue damage. In this study, the clinical and
      scientific impact of indocyanine green (ICG) video angiography was tested in 20
      patients. A wide range of depth of injury and etiology was included and analyzed.
      In all cases considered, video angiography was possible. The measurements and
      observations correlated well with the actual burn depth, which was assessed
      clinically (pre- and intraoperative assessment) and histologically (biopsies). In
      conclusion, ICG video angiography seems to be a practical method to describe
      vascular patency in a burn wound. The results indicate that ICG fluorescence
      angiography is a practical, accurate, and effective adjunct to clinical methods
      for estimating burn wound depth and thereby to assist in the rational assessment
      of treatment options. Furthermore, it allows an objective, qualitative and
      quantitative observation of the dynamic changes in burn wound depth, which are
      observed during the acute post-burn period, thereby indicating optimal timing of
      the first operation.

PMID- 14636753
TI  - Oxandrolone induced lean mass gain during recovery from severe burns is
      maintained after discontinuation of the anabolic steroid.
AB  - Weight loss and lean mass loss from burn induced catabolism can be more rapidly
      restored when the anabolic steroid oxandrolone is added to optimum nutrition
      compared to nutrition alone. Our purpose in this study was to determine whether
      the regained lean body mass (LBM) is retained 6 months after stopping
      oxandrolone. Forty-five severe burn patients, entering the recovery phase were
      randomized into a nutrition group alone or with the addition of oxandrolone, 20mg
      per day upon admission to the acute burn rehabilitation (RH) unit. Oxandrolone
      was discontinued after at least 80% of the involuntary weight loss occurring in
      the acute burn period, was restored. Body composition was measured using
      bioelectric impedence analysis (BIA). We found that patients receiving
      oxandrolone, in the rehabilitation unit, regained weight and lean mass two to
      three times faster than with nutrition alone. The difference was statistically
      significant (P<0.05). All patients were discharged from RH on a nutrition and
      exercise program and monitored in the outpatient burn center. After 6 months,
      body weight and body composition were again measured. We found that the body
      weight and lean mass which was restored during RH, was maintained 6 months after
      discontinuation of oxandrolone. Lost lean mass was not yet restored in the
      nutrition alone group. We can conclude that body weight and lean mass which is
      lost, due to burn induced catabolism, can be effectively restored in the post
      burn recovery period with oxandrolone. The body weight and lost lean mass which
      is regained, is maintained 6 months after stopping the drug.

PMID- 14636754
TI  - Examination of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients with
      burns.
AB  - The FasL-Fas system is one of the recognized apoptosis-inducing systems, and has
      been determined to have important functions in relation to homeostasis and
      biological defense mechanisms. In this study, we investigated the serum levels of
      soluble Fas (sFas), soluble FasL (sFasL) and tumor necrosis factor alpha (TNF
      alpha) in patients with burns. The sFas levels were found to be significantly
      higher in the patients who eventually died as compared to those in the patients
      who survived (3.9+/-1.8ng/ml versus 2.6+/-1.0ng/ml). On the other hand, the sFasL
      levels were significantly higher in the patients who survived (61.5+/-29.9ng/ml
      versus 37.2+/-14.4ng/ml) than in those who eventually died. A positive
      correlation was noted between the TNF-alpha level and the sFas level, and a
      negative correlation was observed between the TNF-alpha level and the sFasL
      level. These findings suggest that worsening of the condition of a burns patient
      may be related to changes in the Fas-FasL system.

PMID- 14636755
TI  - The effects of thermal injury on transcellular permeability and intestinal P
      glycoprotein in rats.
AB  - This study was designed to assess intestinal drug transport via transcellular
      absorption and intestinal P-glycoprotein content following thermal injury in rats
      using propranolol as a marker substrate. Male, Sprague Dawley rats (n=30)
      underwent either a 30% total body surface area full thickness burn or sham
      treatment. Twenty-four hours later, animals were anesthetized, underwent
      laparotomy and the proximal jejunum was cannulated. The jejunal segment was
      perfused with buffer containing [3H] propranolol. Following euthanasia, jejunal
      tissue was harvested for Western immunoblotting of P-glycoprotein and villin, and
      immunohistochemical analysis of P-glycoprotein. Dramatic structural changes in
      jejunal integrity were observed following thermal injury; however, no significant
      differences in the absorption characteristics of propranolol following thermal
      injury were observed. Mean effective permeability of propranolol was 5.67+/-1.79
      and 5.85+/-1.67cm/sx10(-5) for burn and sham groups, respectively (P>0.05). P
      glycoprotein and villin content in the jejunum were significantly decreased in
      burn animals. The transcellular transport of propranolol is unaffected 24h
      following thermal injury in rats, despite alterations in intestinal P
      glycoprotein content. The decrease in P-glycoprotein and villin content in
      thermally injured animals may reflect loss of mature enterocytes at the villus
      tips.

PMID- 14636756
TI  - Serum cholesterol and triglycerides: potential role in mortality prediction.
AB  - The present study was performed in order to evaluate the diagnostic usefulness of
      serial cholesterol and triglycerides measurements in patients with severe burns.
      One of the main objective was to find out if these parameters are clinically
      relevant to determine the morbidity of a burn patient and thereby the patient's
      outcome. In 220 patients with thermal injuries, cholesterol and triglyceride
      concentrations were measured daily. Blood samples were drawn immediately upon
      admission and thereafter daily until patient's discharge or death. For both
      parameters, a characteristic course was noted: in the group of non-survivors, a
      decrease of cholesterol prior to death was noted, while survivors, increased
      prior to discharge. The time courses of both groups (survivors-non-survivors)
      differed statistically significantly (P=0.0068). An increase in triglycerides was
      observed in all non-survivors prior to death, but in the group of survivors
      triglycerides remained more or less unchanged. These time courses also had
      statistically significant differences (P=0.0004). In our 220 patients, changes in
      cholesterol (P<0.0001, hazard ratio 1.02) and triglycerides (P=0.0008, hazard
      ratio 1.01) had comparable capability to predict the severity of a burn trauma
      and thereby its outcome than the established parameters in the treatment of burns
      (total body surface area burned, age, inhalation). We consider the serial
      measurements of cholesterol and triglycerides as clinically relevant to assess
      the morbidity of a patient and thereby to estimate the patient's outcome. We
      think that these serial measurements provide useful information for the clinician
      treating patients with severe burns.

PMID- 14636757
TI  - Burn injuries associated with the water tank of motorfarming tricycles in China.
AB  - Burns caused by hot coolant from the reservoir of motorfarming tricycles have not
      been reported previously. We performed retrospective studies of such cases in 126
      patients with complete records in rural areas of China. The majority of victims
      were unmarried (59.5%), young (<40 years, >20, 55.6%), and male (male to female
      ratio 9:1). The burn accident occurred mostly during the busy seasons of spring
      and summer (66.7%). The mechanism of injury was usually the same. The drivers
      were trapped under the farming tricycle in a traffic accident and then hot
      coolant leaked from the mouth of the coolant, resulting in long contact with the
      hot fluid. The burn wounds were located mostly on the areas of the buttocks and
      lower extremities (especially on the thigh) (64.3%). The generally burned
      patients had moderate burn areas, about 20-50% total burn surface area (TBSA) of
      deep partial thickness or full thickness burn wound. For the purpose of
      decreasing the number of burns presenting, or at least making them less severe,
      the suggestions include: (1) the design of motorfarming tricycle should be
      changed; obviously separation of the coolant tank from the seat is the most
      important factor in reducing such burns. (2) Road conditions should be improved
      to reduce traffic accidents and loading regulations introduced. (3) Traffic
      control should be enhanced, especially in rural areas.

PMID- 14636758
TI  - Role of Rho kinase and actin filament in the increased vascular permeability of
      skin venules in rats after scalding.
AB  - OBJECTIVE: To investigate the role of the Small GTPase Rho and endothelial
      cytoskeleton in the increased vascular permeability of rat skin after scalding.
      METHODS: Rats were subjected to scalding local ventral skin and a venule was
      isolated from scalded skin and cannulated by micropipette. The venular
      permeability was measured with a fluorescence ratio technique and expressed with
      the permeability coefficient to albumin (P(a)). The venular F-actin filaments
      were observed by staining with rhodamine phalloidin and laser confocal scanning
      microscopy. A specific Rho kinase inhibitor Y-27632 was added into vessel bathing
      solution or preincubated with vessels to evaluate the role of Rho kinase in
      regulating of vascular barrier function. RESULTS: Scalding increased P(a) value
      of skin venule about threefold compared to normal skin venules (P<0.01) and was
      maintained for 120 min. Inhibition of Rho kinase with Y-27632 (30 micromol/l in
      low-concentration group; 60 micromol/l in high-concentration group) significantly
      attenuated the hyperpermeability responses to scalding in a dose dependent
      fashion. A prominent peripheral actin rim (PAR) existed at the outer area of
      endothelial cells and apparently delineated the cell-to-cell borders. In the
      control group, the PARs were arranged smoothly and fairly continuously. However,
      occasionally PARs did show focal interruption with focal fluorescein
      isothiocyanate (FITC)-albumin leakage. In the burned group, PARs were less
      organized and accompanied by a large amount of FITC-albumin leakage. Inhibition
      of Rho kinase with Y-27632 dramatically reduced P(a) value with recovery of actin
      filament arrangement in venule after scalding. CONCLUSION: Burn leads to dermal
      venular permeability increase with endothelial cytoskeleton depolymerization and
      disruption. Rho signal transduction pathway is involved in these responses.

PMID- 14636759
TI  - Roles of ischemia and hypoxia and the molecular pathogenesis of post-burn cardiac
      shock.
AB  - OBJECTIVE: To evaluate the roles of ischemia and hypoxia in the development of
      post-burn cardiac shock and its molecular pathogenesis. METHODS: One hundred and
      fifty healthy adult Wistar rats were divided into the control group and burn
      group inflicted with 30% total body surface area third degree burn. Groups were
      processed at 1, 3, 6, 12 and 24h post-burn. Myocardial contractile function,
      myocardial microvascular permeability, volume of regional myocardial blood flow,
      levels of myocardial myosin light chain 1 (CM-LC1), myocardial NF-kappaB (nuclear
      factor kappa B) activity, MPO (myeloperoxidase), TNFalpha (tumor necrosis factor
      alpha) mRNA expression and levels of myocardial TNFalpha were measured. MAIN
      RESULTS: Myocardial microvascular permeability began to rise at 1h post-burn and
      was still rising at 24h (2.1 times as high as that of the control group); the
      volume of regional myocardial blood flow fell significantly and remained at a
      level markedly lower than that in the control group; CM-LC1 also rose
      significantly and reached a level 18.6 times as high as that in the control
      group; myocardial NF-kappaB activity and TNFalpha mRNA expression were
      significantly promoted; elevation of levels of myocardial TNFalpha and MPO
      activity occurred; cardiac mechanic parameters including LVSP, +/-dp/dt max
      significantly decreased while LVEDP increased. CONCLUSION: The findings of the
      present study suggest severe myocardial damage due to ischemia and hypoxia
      following burns; promotion of myocardial NF-kappaB activity and TNFalpha mRNA
      expression in myocardium may be an important factor in the development of post
      burn cardiac shock.

PMID- 14636760
TI  - Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and
      nystatin.
AB  - Inhibition of wound contraction by topical anti microbial agents has been
      described. The purpose of this study was to further investigate that phenomenon
      and to explore the effect that other agents such as Aloe vera might have on this
      process. Full-thickness excised wounds were created on the dorsum of Sprague
      Dawley rats under anaesthesia. The wounds were treated with topical agents three
      times daily for fourteen days, then observed until healed. Groups were: saline
      control, placebo (aqueous cream) control, silver sulphadiazine (SSD) cream 1%,
      SSD 0.5%, SSD 1% with Aloe vera, SSD 1% with nystatin, nystatin. Wound surface
      areas were measured each three days. Time to 50% and 90% healing was compared
      using ANOVA. Wound half-life and healing times were shortest in the SSD/Aloe vera
      and nystatin groups (P<0.05) and longest in the 1% SSD and saline control groups.
      The placebo group (aqueous cream) healed in a significantly shorter time (P<0.05)
      than the control (saline) group. Wound contraction was delayed by saline and SSD.
      Nystatin and Aloe vera, when added to SSD, reversed that effect. These data
      suggest that a dry wound (saline) heals slowly. Infection control without delay
      of wound healing is most appealing and clinical trials are planned.

PMID- 14636761
TI  - The use of a collagen sponge/living cell composite material to treat donor sites
      in burn patients.
AB  - The objective of this study was to examine the safety and efficacy of bilayered
      cellular matrix, (OrCel) Ortec International, Inc., New York, NY in facilitating
      timely wound closure of split-thickness donor sites in severely burned patients.
      We utilized a matched pairs design; each patient had two designated donor sites
      of equivalent surface area and depth. Sites were randomized to receive a single
      treatment of either OrCel or the standard dressing Biobrane-L (Bertek
      Pharmaceuticals) Sugarland, TX. The results demonstrate that OrCel was more
      effective in facilitating timely wound closure of split-thickness skin donor
      sites than Biobrane-L. The healing time for OrCel sites was significantly shorter
      than for sites treated with Biobrane-L. This acceleration of wound healing was
      clinically important in enabling earlier recropping. OrCel sites also exhibited
      reduced scarring. Therefore, treatment of donor site wounds with OrCel is well
      tolerated, promotes more rapid healing, and results in reduced scarring when
      compared with conventional therapy with Biobrane-L.

PMID- 14636762
TI  - Expanded occipito-cervico-pectoral flap for reconstruction of burned cervical
      contracture.
AB  - Postburn neck contracture and hypertrophic scarring can cause functional
      limitation and aesthetic disfigurement. Reconstruction of severe deformities and
      scar of neck following healing from burns confronts the surgeon with some of the
      most challenging problems in reconstructive surgery. Through knowledge of
      available reconstructive technique accurate diagnosis of tissue deficiency and
      secondary distortion, imaginative planning and definitive, careful execution of
      ones surgical plan are the bare minimum items for achieving improvement in a
      burned deformed neck. The aim of this article is to assess the role of expanded
      occipito-cervico-pectoral (o-c-p) flap for reconstruction in a series of four
      patients with severe burn scar of neck and involvement of shoulder back but
      intact anterior aspect of chest. This is an alternative method of reconstruction
      burn scar of neck area.

PMID- 14636763
TI  - A new method: perforator-based tissue expansion for a preexpanded free cutaneous
      perforator flap.
AB  - Recent advances in concepts of preexpanded free flaps have made it possible to
      replace larger postburn contracture area. Free anterolateral thigh (ALT)
      cutaneous perforator flaps are popular due to constant, reliable anatomy and
      various clinical applications in our department. Combination of preexpansion,
      perforator-based prefabrication of tissue expansion and a free anterolateral
      thigh flap is first introduced and developed to resurface the large territory of
      postburn cervical contracture in a 33-year-old female patient with second to
      third degree flame burn with a 45% total body surface area (TBSA) involvement.
      The limited lateral flexion and rotation was noted despite aggressive
      rehabilitation for 6 months. The 650cm(3) kidney-shaped tissue expander was
      inserted around the myocutaneous perforator under the fascia via the midlateral
      thigh incision in first stage. Two months later right lateral neck scar
      (size=25cm x 13cm) was excised after serial clinic saline injection. The
      preexpanded free flap (size=29cm x 15cm) combined with z plasty and capsulectomy
      was harvested and covered in the contracture defect. A flap totally survived. One
      staged resurfacing was achieved with immediate postoperative improvement. The
      hospital stay was 6 days. The donor site was closed primarily. After 6 months
      follow-up, the functional improvement was assessed as follows: an increase in
      rotation of 14 degrees (preoperative 74 degrees to postoperative 88 degrees );
      and an increase in lateral flexion of 10 degrees (preoperative 30 degrees to
      postoperative 40 degrees ). The prefabrication of the free cutaneous perforator
      flap by perforator-based tissue expansion above the muscle has several
      advantages: (1) it provides accurate and safe expansion without damage of any
      perforator compared with the blunt dissection; (2) larger territory of free flaps
      can be used for burn reconstruction; (3) donor site is primarily closed with low
      tension; (4) it is not a random expanded flap due to direct expansion of specific
      skin territory around the perforator. The disadvantages are two-staged
      procedures, complications of tissue expansion (e.g. infection, extrusion), the
      possibility of compression of pedicles.

PMID- 14636764
TI  - The seven flap Z-plasty revisited.
AB  - Although multiple Z-plasties are widely used for burn contractures, the seven
      flap Z-plasty procedure has not gained wide acceptance in plastic surgery
      practice. However, the technique has the advantage of achieving more elongation
      than other Z-plasty techniques. The technique safely performed with satisfactory
      results in 31 cases.

PMID- 14636765
TI  - Subeschar clysis in deep burns.
AB  - Six hundred thirteen patients with deep burn of up to 50% total body surface area
      (TBSA) were treated with 0.25% povidone iodine subeschar clysis (PVP-SEC) in
      addition to surface application of povidone iodine + Neosporin in the form of
      "crust". The results were compared with those of 595 age, sex and percentage of
      burn, matched patients treated only by "crust application". The quantitative
      bacterial count showed significantly less incidence of infection on the 7th and
      8th days post treatment (P<0.001). The organisms identified were predominately
      Staphylcocous aureus and Pseudomonas aeroginosa. Significantly more number of
      patients, with burns up to 50% TBSA, could be grafted within 20 days in the SEC
      group. The graft acceptance rate in this group was 90%.

PMID- 14636766
TI  - Split thickness skin grafting for recreation of the scrotum following Fournier's
      gangrene.
AB  - Fournier's gangrene is an infection of the genitals and perineum that is treated
      with extensive soft tissue debridement, often leading to loss of scrotal skin.
      Multiple options for reconstruction of the scrotum are available. Four cases of
      recreation of the scrotum with meshed split thickness skin grafts (STSG) are
      presented. The discussion includes a comparison of STSG with other treatment
      options. We conclude that STSG are a safe, technically easy treatment option with
      satisfactory cosmetic and functional results.

PMID- 14636767
TI  - MEBO and hot bitumen burns.

PMID- 14636768
TI  - Temporary henna tattooing--a risky procedure. Case report and literature review.

PMID- 14636769
TI  - Mediterranean jellyfish (Rhopilema nomadica) sting.

PMID- 14636770
TI  - Careless staple application and an unexpected image on plain radiograph.

PMID- 14636771
TI  - Always look a Trojan horse in the mouth.

PMID- 14636773
TI  - New discoveries about the second gene for familial hemiplegic migraine, ATP1A2.

PMID- 14636774
TI  - Surgical treatment of tumoral temporal-lobe epilepsy.

PMID- 14636775
TI  - Alzheimer's disease: the glycosaminoglycan sink.

PMID- 14636777
TI  - Cognitive impairment during epileptiform discharges: is it ever justifiable to
      treat the EEG?
AB  - Epileptiform EEG discharges are not confined to people with epilepsy, and their
      frequency is only weakly related to severity. A fundamental principle of EEG
      practice is, therefore, to avoid overinterpretation of epileptiform activity.
      Epileptiform discharges not accompanied by obvious clinical events are generally
      regarded as subclinical or interictal. However, in many patients sensitive
      methods of observation, notably continuous psychological testing, show brief
      episodes of impaired cognitive function during such discharges. This phenomenon
      of transitory cognitive impairment (TCI) is found in about 50% of patients who
      show discharges during testing. TCI is not simple inattention. The effects are
      material and site specific: lateralised discharges are associated with deficits
      of functions mediated by the hemisphere in which the discharges occur.
      Conversely, specific tasks can activate or suppress focal discharges over the
      brain regions that mediate the cognitive activity in question. TCI clearly
      contributes to the cognitive problems of some people with epilepsy and may cause
      deficits that pass unrecognised. TCI is demonstrable in many cases of benign
      partial epilepsy of childhood, a disorder once thought to have no adverse
      psychological effects. TCI can contribute to abnormalities of psychological test
      profiles and interferes with daily tasks, such as reading and driving. In
      children it may be associated with behavioural disorders. An important practical
      issue is whether TCI materially impairs psychosocial function and, if so, whether
      drug treatment is desirable or effective. Uncontrolled reports and two
      preliminary randomised controlled trials of antiepileptic treatment of TCI have
      suggested that suppression of discharges is associated with significant
      improvement in psychosocial function.

PMID- 14636778
TI  - Dystrophin and mutations: one gene, several proteins, multiple phenotypes.
AB  - A large and complex gene on the X chromosome encodes dystrophin. Many mutations
      have been described in this gene, most of which affect the expression of the
      muscle isoform, the best-known protein product of this locus. These mutations
      result in the Duchenne and Becker muscular dystrophies (DMD and BMD). However,
      there are several other tissue specific isoforms of dystrophin, some exclusively
      or predominantly expressed in the brain or the retina. Mutations affecting the
      correct expression of these tissue-specific isoforms have been associated with
      the CNS involvement common in DMD. Rare mutations also account for the allelic
      disorder X-linked dilated cardiomyopathy, in which dystrophin expression or
      function is affected mostly or exclusively in the heart. Genotype definition of
      the dystrophin gene in patients with dystrophinopathies has taught us much about
      functionally important domains of the protein itself and has provided insights
      into several regulatory mechanisms governing the gene expression profile. Here,
      we focus on current understanding of the genotype-phenotype relation for
      mutations in the dystrophin gene and their implications for gene functions.

PMID- 14636779
TI  - In-hospital stroke.
AB  - Between 6.5% and 15.0% of all strokes occur in patients already in hospital, many
      of whom are there for surgical procedures or cardiac disorders. This important
      group of patients could potentially be assessed more rapidly than others and
      could be candidates for interventional therapies. However, delays in recognition
      and assessment are common, possibly related to comorbidities and the complexities
      of hospital practice. Risk factors for in-hospital stroke include specific
      operations and procedures (eg, cardiac surgery), previous medical disorders
      (especially a history of stroke), and certain physiological characteristics
      (including fever and dehydration). The stroke subtype is embolic in a large
      proportion, and there are various possible precipitating mechanisms. Outcome can
      be poor, with high mortality. Interventional therapies, particularly
      thrombolysis, are possible options. In the postoperative setting, intra-arterial
      thrombolysis is feasible and reasonably safe in carefully selected patients.
      Experimental agents and the manipulation of physiological variables are other
      treatment possibilities that could be applied early in this group of patients.
      Increasing the awareness by hospital physicians of such interventions may be an
      important factor that reduces delays in assessment of patients who have stokes
      while in hospital.

PMID- 14636780
TI  - Functional roles and therapeutic targeting of gelatinase B and chemokines in
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown cause.
      Pathogenetic mechanisms, such as chemotaxis, subsequent activation of
      autoreactive lymphocytes, and skewing of the extracellular proteinase balance,
      are targets for new therapies. Matrix metalloproteinase gelatinase B (MMP-9) is
      upregulated in MS and was recently shown to degrade interferon beta, one of the
      drugs used to treat MS. Consequently, the effect of endogenously produced
      interferon beta or parenterally given interferon beta may be increased by
      gelatinase B inhibitors. Blockage of chemotaxis or cell adhesion molecule
      engagement, and inhibition of hydroxymethyl-glutaryl-coenzyme-A reductase to
      lower expression of gelatinase B, may become effective treatments of MS, alone or
      in combination with interferon beta. This may allow interferon beta to be used at
      lower doses and prevent side-effects.

PMID- 14636781
TI  - Human prion diseases: epidemiology and integrated risk assessment.
AB  - Human prion diseases are devastating and incurable, but are very rare. Fears that
      the bovine spongiform encephalopathy epizootic would lead to a large epidemic of
      its presumed human counterpart, variant Creutzfeldt-Jakob disease (vCJD), have
      not been realised. Yet a feeling of uncertainty prevails in the general public
      and in the biomedical world. The lack of data on the prevalence of asymptomatic
      carriers of vCJD compounds this uncertainty. In addition to this problem,
      Switzerland is currently faced with another issue of major public concern: a
      recent rise in the incidence of CJD. Here we examine the plausibility of several
      scenarios that may account for the increase in CJD incidence, including
      ascertainment bias due to improved reporting of CJD, iatrogenic transmission, and
      transmission of a prion zoonosis. In addition, we present the design and current
      status of a Swiss population-wide study of subclinical vCJD prevalence.

PMID- 14636782
TI  - Epilepsy at the movies: possession to presidential assassination.
AB  - In this review I examine the portrayal of epilepsy, seizures, and non-epileptic
      attack disorder in 62 movies produced over three-quarters of a century, across
      four continents, covering nine cinematic genres. While similar reviews of
      epilepsy in literature have suggested a progression in the understanding of
      epilepsy over time, this survey of the newer medium found examples of all of the
      ancient beliefs about epilepsy including demonic or divine possession, genius,
      lunacy, delinquency, and general "otherness". Nevertheless there has been a
      progressive trend towards more overt depictions of epilepsy. Male characters with
      idiopathic epilepsy tend to be mad, bad, and commonly dangerous, whereas
      characters with post-traumatic epilepsy are usually cast as heroes triumphing
      against the odds. Epilepsy in female characters tends to signify exotic
      vulnerability. The dramatic potential of seizures remains highly tempting to film
      writers and directors alike. Although it is not for the medical profession to
      dictate or censor cinematic content, a keen eye on these depictions will help us
      to understand and perhaps combat some of the stereotypes and myths that continue
      to surround epilepsy in the 21st century.

PMID- 14636785
TI  - Monkey business.

PMID- 14636786
TI  - Differences in health complaints among university students from three European
      countries.
AB  - BACKGROUND: The purpose of this research was to assess the prevalence of somatic
      and psychosomatic health complaints in a cross-national population of university
      students and to study risk factors associated with health complaints. METHODS:
      The analysis was based on samples of first-year students from Pamplona (Spain),
      Bielefeld (Germany), and Kaunas (Lithuania). The total sample included 2343
      students. Ten health complaints were measured by a symptom checklist with a self
      administered questionnaire. Sociodemographic and lifestyle data were also
      collected. Factor analysis was employed to develop three complaint scores.
      RESULTS: Multifactorial logistic regression analysis revealed substantial
      associations between the factors female gender and psychosocial stress and high
      levels (>median) of complaint scores. Furthermore, after adjustment for age, sex,
      and lifestyle variables Lithuanian students were less likely to report
      gastrointestinal complaints (OR 0.62, CI 0.43-0.90) and neck ache/backache (OR
      0.41, CI 0.28-0.61) compared to Spanish students. In addition, German students
      were less likely to report psychosomatic (OR 0.49, CI 0.35-0.69) and
      gastrointestinal complaints (OR 0.47, CI 0.34-0.65) than their Spanish peers.
      CONCLUSIONS: Although the results cannot be generalized to the general population
      of the respective countries, the different profiles of reported complaints should
      give rise to special interventions in this young population.

PMID- 14636787
TI  - The effects of state counterindustry media campaigns on beliefs, attitudes, and
      smoking status among teens and young adults.
AB  - OBJECTIVES: This study sought to identify the pathways through which state-funded
      counterindustry media campaigns influence beliefs and attitudes regarding tobacco
      industry practices and smoking status. METHODS: A national random-digit-dial
      telephone survey of 6875 youths 12 to 24 years old was conducted in Winter 1999
      2000. Exploratory and confirmatory factor analysis investigated the structure
      underlying beliefs and attitudes toward the tobacco industry. Structural equation
      modeling tested whether the data were consistent with a theoretically based
      causal model of campaign effects from exposure to an aggressive counterindustry
      campaign, mediated by beliefs about tobacco industry practices and attitudes
      toward the tobacco industry, to smoking status. RESULTS: Exploratory and
      confirmatory factor analysis indicated that two dimensions underlie perceptions
      of the tobacco industry: beliefs about tobacco industry practices and attitudes
      toward the industry. Structural equation models provided strong support for the
      hypothesized model: youth living in states with aggressive counterindustry media
      campaigns had more negative beliefs about tobacco industry practices, which led
      to negative attitudes toward the industry and less progression along a continuum
      of smoking intentions and behavior. CONCLUSIONS: Media campaigns using
      counterindustry messages show promise in reducing smoking behavior among teens
      and young adults by changing beliefs about industry practices.

PMID- 14636788
TI  - School-based obesity screening in rural Appalachia.
AB  - BACKGROUND: Although identification of obesity during childhood is strongly
      recommended for the prevention of adult disease, access to obesity screening for
      children is almost exclusively through physicians' office visits. We examined the
      feasibility and utility of conducting a school-based obesity and cardiovascular
      disease (CVD) risk factor screening program in a rural Appalachian population.
      METHODS: Height, weight, blood pressure, total cholesterol (TC), and high-density
      lipoprotein (HDL) cholesterol were measured in 1338 fifth-grade children (631
      boys and 707 girls) in 14 rural West Virginia counties in 2000-2001. RESULTS: We
      found a high prevalence of overweight (17.5%) and obesity (27.0%). Compared with
      non-overweight children, obese children had greater risk of high TC (OR 2.4), low
      HDL cholesterol (OR 5.3), high systolic blood pressure (OR 3.3), and high
      diastolic blood pressure (OR 2.4) (all OR >1.0, P < 0.05). Only 63% of obese and
      26% of overweight children were identified by their physician as having a weight
      above recommended values. CONCLUSIONS: The high prevalence of obesity, the
      associated clustering of CVD risk factors, and the low obesity identification
      rate by physicians suggest that alternative approaches to obesity screening, such
      as universal school-based programs, may be warranted in high-risk communities.

PMID- 14636789
TI  - Groningen Active Living Model (GALM): stimulating physical activity in sedentary
      older adults; validation of the behavioral change model.
AB  - BACKGROUND: A significant proportion of older adults in The Netherlands do not
      participate regularly in leisure-time physical activity. The Groningen Active
      Living Model (GALM) was developed to change this situation for the better.
      Longitudinal results of the validation of the GALM behavioral change model are
      presented. METHODS: We obtained data on potentially mediating variables of
      physical activity behavior change (self-efficacy, social support, perceived
      fitness, and enjoyment) from 96 participants in a prospective study during the 18
      months the GALM strategy lasted. RESULTS: Prospective analyses revealed
      significant differences in several potentially mediating variables, although some
      of these differences were contrary to our hypothesis. Discriminant analysis
      resulted in canonical correlations of 0.50 after 6 months and 0.66 after 18
      months of program participation between adherers and nonadherers, respectively;
      73.8 and 80.0% of the subjects were classified correctly. CONCLUSIONS: Based on
      the results, it can be concluded that we partially succeeded in manipulating the
      potentially mediating variables by means of our GALM strategy. Several mediating
      variables were identified that reliably discriminated long-term adherers from
      nonadherers, expanding the generalizability of social cognitive theory-driven
      variables to a Dutch population.

PMID- 14636790
TI  - The Ashkelon Hypertension Detection and Control Program (AHDC Program): a
      community approach to reducing cardiovascular mortality.
AB  - BACKGROUND: Blood pressure (BP) reduction is crucial in reducing cardiovascular
      (CV) morbidity and mortality in the community. Subjects aged 20-65 seldom visit
      the primary care clinics, so they are unlikely to be detected without an active
      outreach screening program. The aim of the project was to prepare a professional
      doctor-nurse screening team, who will instruct those found to be at high risk in
      control of their risk factors, in order to reduce CV morbidity and mortality.
      METHODS: During a 10-year period (1980-1990), teams examined 12,202 subjects,
      (mean age 51 +/- 7 years, range 20-65 years) accounting for 23.4% of the total
      regional population. High risk subjects underwent an intensive CV risk factor
      control program. RESULTS: Subjects (3,506 or 28.6%) were found to have one or
      more CV risk factors (hypertension, obesity, smoking, hypercholesterolemia).
      During an average of 2 years, follow-up BP, weight reduction, and smoking
      cessation remained statistically significant. Total cholesterol was unchanged.
      Over this period, the standardized mortality ratio (SMR) in the area for acute MI
      fell from 100 to 76 (P < 0.01), for CV disease from 129 to 107 (P < 0.0001), and
      for hypertension from 121 to 87 (P < 0.1 NS). The project saved many life-years
      at no additional net cost to society, and cost effectiveness analysis showed
      positive results. CONCLUSIONS: A community approach with mainly
      nonpharmacological treatment is feasible and cost effective in reducing CV
      morbidity and mortality.

PMID- 14636791
TI  - Sun exposure and sun protection behaviours among Australian adolescents: trends
      over time.
AB  - BACKGROUND: This study compared the sun exposure and sun protection behaviours of
      adolescent students between 1993 and 1999. METHODS: Schools from all Australian
      states and the two territories participated in each of the 1993, 1996, and 1999
      surveys and a sample of students from years 7 to 12 were surveyed. In each of the
      states and territories a random sample of schools was selected within each
      education sector (government, Catholic, independent). The questionnaire was a
      self-completed booklet with questions about sunburn history during the previous
      summer, tan preferences, skin-type, and usual reported behaviour. Data from a
      total of 78,032 students were available for analysis. RESULTS: From 1993 to 1999
      there was a significant increase in the number of students reporting sunburn
      during the previous summer (chi(2) = 225.77, df = 2, P < 0.01). However, the
      percentage of students who preferred no tan at all increased over the same period
      (chi(2) = 184.47, df = 2, P < 0.01). The percentage of students who usually or
      always wore clothing that covered most of their body decreased between 1993 and
      1999 (chi(2) = 20.46, df = 2, P < 0.01); the percentage of students usually or
      always wearing maximum protection sunscreen decreased over time (chi(2) = 27.71,
      df = 2, P < 0.01). Staying in the shade increased from 1993 (26%) to 1996 (32%)
      but decreased slightly in 1999 (30%). Across all survey years, only 11% of
      students routinely followed all three protective behaviours of wearing a hat,
      sunscreen, and clothes that cover the body. CONCLUSIONS: Sun protection practices
      among adolescents are still below optimal levels. Future educational programs
      require innovative approaches that aims to change attitudes toward tanning as
      being healthy and attractive and modify adolescent behaviours in relation to sun
      exposure.

PMID- 14636792
TI  - Predictors of regular Pap smears among Korean-American women.
AB  - BACKGROUND: Many Korean-American women (KAW) are unaware of the importance of
      regular cancer screening. This research estimates rates and examines predictors
      of regular cervical cancer screening among KAW. METHODS: Face-to-face surveys
      were conducted with 459 KAW residing in Maryland. Study participants were
      recruited through Korean churches and senior housing. RESULTS: Thirty-nine
      percent of women had regular Pap smears. Regular Pap smear rates varied with age,
      with women 65 years and older least likely to have regular Pap smears. In
      multiple logistic regression, the strongest correlate of regular Pap smear was
      knowledge of guidelines. Physician recommendation, having health insurance, and
      having friends or family members receiving Pap smears were also important
      facilitators. Spoken English proficiency interacted with education for an
      outcome; women with a low level of education and low English proficiency had
      lower rates of Pap smears than those who had a high level of education and high
      proficiency. The most frequently given reason for lack of a regular Pap smear was
      a belief that screening was unnecessary if a woman had no symptoms of cervical
      cancer. CONCLUSIONS: Strategies for education on screening guidelines, along with
      physician referrals, should be implemented. Culturally appropriate educational
      programs about cervical cancer screening should be developed for less educated
      and less acculturated immigrant women.

PMID- 14636793
TI  - Environmental interventions to promote vegetable and fruit consumption among
      youth in school settings.
AB  - BACKGROUND: This paper reviews the available literature on the school food
      environment with a focus on identifying effective strategies to promote vegetable
      and fruit (VF) consumption among youth in school settings. METHODS: Studies were
      identified through a search of electronic databases as well as references cited
      within published articles. Seven studies were identified that evaluated changes
      in VF intake and included a control group. Four additional school-based
      interventions were reviewed that focused on changes in VF intake as part of a
      multibehavior intervention. RESULTS: Multicomponent school interventions have
      been effective in increasing F intake, with reported increases ranging from 0.2
      to 0.6 servings per day. Impact on V intake has been less effective, with
      increases ranging from 0 to 0.3 servings per day. Total VF increases ranged from
      0 to 0.6 servings per day. Results of environmental-only, school-based
      interventions have shown positive effects on students' choice of targeted foods.
      CONCLUSIONS: Environmental change interventions in schools show potential for
      positively affecting VF consumption among youth.

PMID- 14636795
TI  - A randomized trial of a family-based smoking prevention intervention in managed
      care.
AB  - BACKGROUND: Each day more than 2000 youth under age 18 become daily smokers and
      the age of tobacco initiation has been going down. Health care settings can
      partner with families to encourage parent-child interactions that prevent youth
      tobacco use. This study evaluates a smoking prevention intervention package for
      parents and children (aged 10-12) provided through their managed care
      organization. METHODS: A two-arm (usual care vs intervention) randomized trial
      was employed. The intervention included a mailed parental smoking prevention kit,
      outreach follow-up telephone calls to the parent by a health educator, child
      materials, medical record cues for physicians to deliver prevention messages, and
      parent newsletter. Outcome measures were susceptibility to smoking,
      experimentation with smoking, and smoking in the past 30 days as assessed by 20
      month follow-up surveys of children. RESULTS: A total of 4,026 families enrolled
      in the study. The response rate to the 20-month follow-up was 88%. There were no
      significant effects of the intervention on any of the primary outcomes. The
      intervention was associated with modest but statistically significant increases
      in parent-child discussions of smoking related topics. CONCLUSIONS: A minimal
      intensity family-based prevention program did not significantly reduce rates of
      susceptibility or tobacco use among youth aged 10-12 at baseline and 11 to 14 at
      follow-up. Development and evaluation of innovative approaches to tobacco use
      prevention must continue, despite our disappointing results. Parents and health
      care systems are too important to abandon as channels for prevention messages.

PMID- 14636794
TI  - Association of anthropometric measures with risk of diabetes and cardiovascular
      disease in Hispanic and Caucasian adolescents.
AB  - BACKGROUND: Hispanics are disproportionately affected by the obesity epidemic in
      the United States. Obesity is a primary risk factor for the development of
      cardiovascular disease (CVD) and Type 2 diabetes, which are problematic in
      Hispanic adults. There are limited data relating obesity status in Hispanic
      adolescents to diabetes and CVD risk. METHODS: We studied 115 lean and obese
      adolescents (89 Hispanic, 26 Caucasian), ranging in body mass index (BMI) from 15
      to 52 kg/m(2). We assessed the relationships between four anthropometric indices
      of obesity and risk factors for Type 2 diabetes (insulin (INS), glucose (GLU)),
      and CVD (total cholesterol, triglycerides, HDL, and systolic (SBP) and diastolic
      (DBP) blood pressure). RESULTS: All anthropometric indices were positively
      correlated with total cholesterol, triglycerides, log(INS), GLU, SBP, and DBP,
      and negatively correlated with HDL. Correlations and multiple regression analyses
      indicated that weight and waist circumference (WC) were generally the best single
      predictors of disease risk. Using more than one anthropometric measure in
      multiple regression did not improve predictions of risk over using a single
      predictor. CONCLUSIONS: These results indicate that overweight adolescents
      (particularly Hispanics) are at risk for developing Type 2 diabetes and CVD, and
      that WC and weight are useful for identifying those at particular risk.

PMID- 14636796
TI  - Colorectal cancer screening attitudes and behavior: a population-based study.
AB  - BACKGROUND: Even though colorectal cancer (CRC) screening tests for persons 50
      years of age or over are recommended to reduce colorectal cancer mortality,
      screening rates remain disturbingly low. METHODS: Using random digit dialing, 355
      telephone interviews were conducted with black and white men and women, 50-79
      years of age, who resided in Genesee County, Michigan. The Health Belief Model
      provided the framework to assess attitudes and practices regarding CRC screening.
      RESULTS: For both endoscopic procedures, significantly higher percentages of
      whites than blacks were aware of the screening procedure (P < 0.05). Overall,
      fewer than 30% of respondents were adherent to current CRC screening guidelines.
      Adherence was lowest for black females: 21% for fecal occult blood test, 20% for
      flexible sigmoidoscopy, and 12% for colonoscopy. Black males compared to black
      females were about 2.8 times more likely to have had either flexible
      sigmoidoscopy or colonoscopy (P < 0.05). Physician recommendation was a powerful
      motivator to screening. Two consistent barriers to screening were the belief
      that: (a) the test is not needed; and (b) the test is embarrassing. CONCLUSIONS:
      Interventions directed at physicians and patients are essential to enhance CRC
      screening rates. CRC survival rates may be improved by physician-guided promotion
      of screening that focuses on identified barriers.

PMID- 14636797
TI  - Developing an empirical typology for regular exercise.
AB  - BACKGROUND: Tailored interventions require the identification of distinct
      homogenous subgroups that will benefit from different intervention materials. One
      way to identify such subgroups is to use cluster analysis to identify an
      empirical typology. METHODS: A sample of 346 adults completed surveys through a
      telephone interview that included questions related to participating in regular
      exercise. The three variables used in the cluster analysis were the Pros of
      Exercise, the Cons of Exercise, and Exercise Self-Efficacy. RESULTS: Six
      resulting clusters were labeled Disengaged, Immotive, Relapse Risk, Early Action,
      Maintainers, and Habituated. A series of analyses tested the internal and
      external validity of the typology. The internal validity test revealed that four
      of the clusters demonstrated high stability and replicability, while the Relapse
      Risk and Early Action clusters were less stable. Differences among clusters on
      self-reported exercise behavior and a strong association with stage of change for
      regular exercise provided external validity evidence of the typology.
      CONCLUSIONS: The resulting typology reflects a range of motivational patterns
      that are likely to be responsive to different types of messages and strategies
      regarding adoption and maintenance of regular exercise. The typology also
      generates a number of hypotheses about the identified clusters that can be
      empirically tested in further studies.

PMID- 14636799
TI  - The development of SisterTalk: a cable TV-delivered weight control program for
      black women.
AB  - Overweight and obesity have reached epidemic proportions in the United States,
      with black women disproportionately affected. SisterTalk is a weight control
      program designed specifically for delivery to black women via cable TV. The
      theoretical and conceptual frameworks and formative research that guided the
      development and cultural tailoring of SisterTalk are described. Social Action
      Theory was applied in the development of SisterTalk along with a detailed
      behavioral analysis of the way that black women view weight and weight loss
      within the context of their cultural and social realities. The entire
      intervention development process was framed using this information, rather than
      by changing only superficial aspects of program delivery. Community networking
      and both qualitative and quantitative interview techniques from the fields of
      social marketing and cultural anthropology were used to involve black women from
      Boston in the design and implementation of a program that would be practical,
      appealing, and culturally sensitive. Also discussed are strategies for evaluating
      the program, and lessons learned that might have broader applicability are
      highlighted. The development of the SisterTalk program could provide a useful
      starting point for development of successful weight control programs for black
      women in other parts of the United States as well as for other ethnic and racial
      groups.

PMID- 14636798
TI  - The relative efficacy of pamphlets, CD-ROM, and the Internet for disseminating
      adolescent drug abuse prevention programs: an exploratory study.
AB  - BACKGROUND: Despite the availability of an increasing array of empirically
      validated adolescent drug abuse prevention programs, program materials and
      evaluation findings are poorly disseminated. CD-ROM and the Internet hold promise
      for disseminating this information to schools and agencies that directly serve
      youth, and to policy-making bodies that exercise control over funds to support
      adolescent drug abuse prevention programming. However, data on the relative
      efficacy of these newer technologies over conventional print means of
      dissemination are lacking. METHODS: Recruited through schools, community
      agencies, and policy-making bodies, 188 professionals were randomized to receive
      prevention program materials via pamphlets (55 participants), CD-ROM (64
      participants), and the Internet (69 participants). Participants completed
      pretest, posttest, and 6-month follow-up measures that assessed their access to
      prevention program materials; self-efficacy for identifying, obtaining, and
      recommending these programs; and their likelihood of requesting, implementing,
      and recommending prevention programs to their constituents. RESULTS: Participants
      exposed to dissemination via CD-ROM and the Internet evidenced the greatest short
      and long-term gains on accessibility, self-efficacy, and behavioral intention
      variables. CONCLUSIONS: CD-ROM and the Internet are viable means for
      disseminating adolescent drug abuse prevention programs to schools, community
      agencies, and policy-making bodies, and should be increasingly used for
      dissemination purposes.

PMID- 14636800
TI  - Screening for homocysteine levels in Israel in primary care clinics: a need for
      guidelines.
AB  - BACKGROUND: Elevated total homocysteine (tHcy) levels (>/= 15 micromol/L),
      resulting from enzyme or vitamin deficiency, increase risk for cardiac, cerebral,
      and peripheral vascular disease. This study examines tHcy levels in an Israeli
      population and the relationship to vitamin status and disease. The need for
      screening guidelines is discussed. METHODS: Fasting blood was tested for tHcy
      levels in 262 patients (141 male, 121 female) presenting to two primary care
      clinics. Levels of folic acid and vitamin B12 were examined as well. RESULTS:
      Elevated tHcy levels (>/= 15 micromol/L) were found in 43 of the males (30.5%)
      and four of the female patients (3.3%, P < 0.005), while females had higher
      levels of both vitamin B12 and folic acid. Those with elevated tHcy levels tended
      to be older and with lower vitamin levels, with a higher frequency of coronary
      artery disease. CONCLUSIONS: Screening for tHcy and fortification of grain
      products with folic acid is a cost-effective means for preventing disease. Serum
      tHcy levels are inversely related to vitamin status, and higher levels among
      males is thought to be due to metabolic differences between the genders.
      Guidelines for screening for tHcy in Israel should be established, and
      fortification of grain products implemented.

PMID- 14636801
TI  - Does participation in an epidemiological study improve appropriate prescription
      of screening mammography for asymptomatic women?
AB  - BACKGROUND: To analyze the effect of participating in an epidemiological study on
      quality of care (i.e., appropriate prescription of mammographic screening), we
      have analyzed data collected in the framework of a cross-sectional study
      conducted in Italy among women attending menopause clinics. METHODS: In 1997, a
      large cross-sectional study was organized on the characteristics of women who
      attended a network of first-level outpatient clinics for general counseling about
      menopause or treatment of menopausal symptoms. Women consecutively observed
      during the study were eligible, and the protocol did not set any exclusion
      criteria. All women who agreed to participate underwent a gynecological
      examination and were asked about their general characteristics and lifestyle
      habits, reproductive and menstrual history, and selected medical history.
      Laboratory and instrumental tests were required on clinical grounds; the protocol
      did not consider any test mandatory for all women, but all centers were asked to
      collect information on the examinations prescribed as routine clinical practice.
      The study began in 1997 in 25 centers. By March 1999, the number of centers had
      increased to 268 of which 63 were in the north, 81 in the center, and 124 in the
      south of Italy. Fewer than 3% of eligible women refused to participate. The study
      included 48,444 women. The present analysis looked at current attitudes toward
      screening mammography (SM) in asymptomatic women, as prescribed by gynecologists
      in menopausal centers in Italy. RESULTS: A SM was correctly requested in 55.6% of
      women who entered the study during the second semester of 1997. This rose to
      72.8% by July-August 2000. The correct prescription of a SM was slightly higher
      in current users of hormonal replacement therapy (HRT) and lower in women aged 45
      50 years, the differences being significant (P < 0.05). CONCLUSIONS: These
      results show that appropriate requests for SM increased in centers participating
      in a collaborative epidemiological study on menopause in Italy over a 3-year
      period.

PMID- 14636802
TI  - The confusion over hormonal replacement therapy (Prempro).

PMID- 14636803
TI  - Introduction. Pathways, an intervention trial for the primary prevention of
      obesity in American Indian schoolchildren.

PMID- 14636804
TI  - Obesity in American-Indian children: prevalence, consequences, and prevention.
AB  - BACKGROUND: American Indians of all ages and both sexes have a high prevalence of
      obesity. The health risks associated with obesity are numerous and include Type 2
      diabetes mellitus, hypertension, dyslipidemia, and respiratory problems. Obesity
      has become a major health problem in American Indians only in the past few
      generations and it is believed to be associated with the relative abundance of
      high-fat, high-calorie foods and the rapid change from active to sedentary
      lifestyles. METHODS: The authors reviewed selected literature on prevalence of
      obesity in American-Indian children, and health consequences of obesity. RESULTS:
      Obesity is now one of the most serious public health problems facing American
      Indian children, and it has grave implications for the immediate and long-term
      health of American-Indian youth. Unless this pattern is reversed, American-Indian
      populations will be burdened by an increased incidence of chronic diseases.
      Intervention studies are urgently needed in American-Indian communities to
      develop and test effective strategies for obesity prevention and treatment.
      CONCLUSIONS: To be effective, educational and environmental interventions must be
      developed with full participation of the American-Indian communities.

PMID- 14636805
TI  - Design, implementation, and quality control in the Pathways American-Indian
      multicenter trial.
AB  - BACKGROUND: Pathways was the first multicenter American-Indian school-based study
      to test the effectiveness of an obesity prevention program promoting healthy
      eating and physical activity. METHODS: Pathways employed a nested cohort design
      in which 41 schools were randomized to intervention or control conditions and
      students within these schools were followed as a cohort (1,704 third graders at
      baseline). The study's primary endpoint was percent body fat. Secondary endpoints
      were levels of fat in school lunches; time spent in physical activity; and
      knowledge, attitudes, and behaviors regarding diet and exercise. Quality control
      (QC) included design of data management systems which provided standardization
      and quality assurance of data collection and processing. Data QC procedures at
      study centers included manuals of operation, training and certification, and
      monitoring of performance. Process evaluation was conducted to monitor dose and
      fidelity of the interventions. Registration and tracking systems were used for
      students and schools. RESULTS: No difference in mean percent body fat at fifth
      grade was found between the intervention and control schools. Percent of calories
      from fat and saturated fat in school lunches was significantly reduced in the
      intervention schools as was total energy intake from 24-hour recalls. Significant
      increases in self-reported physical activity levels and knowledge of healthy
      behaviors were found for the intervention school students. CONCLUSIONS: The
      Pathways study results provide evidence demonstrating the role schools can play
      in public health promotion. Its study design and QC systems and procedures
      provide useful models for other similar school based multi- or single-site
      studies.

PMID- 14636806
TI  - Pathways curriculum and family interventions to promote healthful eating and
      physical activity in American Indian schoolchildren.
AB  - BACKGROUND: Pathways, a multisite school-based study aimed at promoting healthful
      eating and increasing physical activity, was a randomized field trial including
      1704 American Indian third to fifth grade students from 41 schools (21
      intervention, 20 controls) in seven American Indian communities. METHODS: The
      intervention schools received four integrated components: a classroom curriculum,
      food service, physical activity, and family modules. The curriculum and family
      components were based on Social Learning Theory, American Indian concepts, and
      results from formative research. Process evaluation data were collected from
      teachers (n=235), students (n=585), and families. Knowledge, Attitudes, and
      Behavior Questionnaire data were collected from 1150 students including both
      intervention and controls. RESULTS: There were significant increases in knowledge
      and cultural identity in children in intervention compared to control schools
      with a significant retention of knowledge over the 3 years, based on the results
      of repeating the third and fourth grade test items in the fifth grade. Family
      members participated in Family Events and take-home activities, with fewer
      participating each year. CONCLUSION: A culturally appropriate school intervention
      can promote positive changes in knowledge, cultural identity, and self-reported
      healthful eating and physical activity in American Indian children and
      environmental change in school food service.

PMID- 14636807
TI  - Changes in the nutrient content of school lunches: results from the Pathways
      study.
AB  - BACKGROUND: Pathways, a randomized trial, evaluated the effectiveness of a school
      based multicomponent intervention to reduce fatness in American-Indian
      schoolchildren. The goal of the Pathways food service intervention component was
      to reduce the fat in school lunches to no more than 30% of energy from fat while
      maintaining recommended levels of calories and key nutrients. METHODS: The
      intervention was implemented by school food service staff in intervention schools
      over a 3-year period. Five consecutive days of school lunch menu items were
      collected from 20 control and 21 intervention schools at four time periods, and
      nutrient content was analyzed. RESULTS: There was a significantly greater mean
      reduction in percent energy from fat and saturated fat in the intervention
      schools compared to the control schools. Mean percentages of energy from fat
      decreased from 33.1% at baseline to 28.3% at the end of the study in intervention
      schools compared to 33.2% at baseline and 32.2% at follow-up in the control
      schools (P<0.003). There were no statistically significant differences for
      calories or nutrients between intervention and control schools. CONCLUSIONS: The
      Pathways school food lunch intervention documented the feasibility of
      successfully lowering the percent of energy from fat, as part of a coordinated
      obesity prevention program for American-Indian children.

PMID- 14636808
TI  - Impact of the Pathways food service intervention on breakfast served in American
      Indian schools.
AB  - BACKGROUND: Pathways was a multisite, multicomponent obesity prevention
      intervention for American-Indian schoolchildren. The goal of the school breakfast
      and lunch component was to reduce fat content of school meals to 30% or fewer
      calories from fat without compromising dietary quality. METHODS: An intensive 3
      year intervention was implemented with school food service staff. Five
      consecutive days of school breakfast menu and recipe information was collected at
      20 control and 19 intervention schools at four time intervals. Data were analyzed
      at nutrient and (in final year) food levels. RESULTS: Average total fat decreased
      in intervention schools from 16.0 grams at baseline to 13.6 grams by end of
      study, compared with 16.6 and 16.7 grams at baseline and final measurement in
      control schools (P<0.030). Percentage of calories from saturated fat were also
      significantly reduced from 12.0 to 8.9%, compared with 12.1 to 10.6% in control
      schools (P<0.014). There were no significant differences in total energy or other
      nutrients by treatment condition across four time points. Food-level data
      revealed a consistent pattern of more lower-fat items served in intervention
      schools compared to control schools. CONCLUSIONS: Pathways was successful in
      achieving its overall goal of reducing dietary fat in meals served for school
      breakfasts.

PMID- 14636809
TI  - Impact of the Pathways intervention on dietary intakes of American Indian
      schoolchildren.
AB  - BACKGROUND: The Pathways study was a randomized, 3-year trial of obesity
      prevention in American Indian Children. An important goal of the Pathways
      intervention was to significantly decrease the percentage of calories eaten as
      fat by the intervention children, relative to controls. This paper reports the
      effects of the Pathways intervention on dietary intake. METHODS: Two types of
      dietary data were analyzed from random samples of children in 41 schools: direct
      observation of school lunch intake at baseline (2nd grade) and follow-up (5th
      grade) (n=470), and 24-hour dietary recalls at follow-up only (n=620). Nutrient
      contents of school meals and recalls were calculated by NDS and NDS-R software
      (University of Minnesota), using vendor products and recipes from each school.
      RESULTS: Based on lunch observations, the intervention was associated with
      significant decreases in mean percentage of calories from total fat (3.6%) and
      saturated fat (2.1%) relative to controls, and a significant increase in the
      percentage of calories from total carbohydrate (3.7%). Compared with the control
      children, intervention children reported significantly smaller 24-hour intakes of
      energy (263 kcal), protein (9.5 g), total fat (15.1 g), saturated fat (6.0 g),
      and polyunsaturated fat (2.3 g); and as a percent of calories, total fat (2.5%)
      and saturated fat (1.1%). Mean intake of carbohydrates as a percentage of
      calories was significantly greater in intervention children by 2.5%, compared
      with controls. CONCLUSIONS: The Pathways intervention successfully reduced the
      intake of percent calories from fat and saturated fat, at school lunch and over
      the whole day.

PMID- 14636810
TI  - The effects of the Pathways Obesity Prevention Program on physical activity in
      American Indian children.
AB  - BACKGROUND: Inadequate opportunities for physical activity at school and overall
      low levels of activity contribute to the high prevalence of overweight and
      obesity in American-Indian children. METHODS: A school-based physical activity
      intervention was implemented which emphasized increasing the frequency and
      quality of physical education (PE) classes and activity breaks. Changes in
      physical activity were assessed using the TriTrac-R3D accelerometer in a
      subsample of 580 of the students (34%) randomly selected from the Pathways study
      cohort. Baseline measures were completed with children in second grade. Follow-up
      measurements were obtained in the spring of the fifth grade. RESULTS:
      Intervention schools were more active (+6.3 to +27.2%) than control schools at
      three of the four sites, although the overall difference between intervention and
      control schools (approximately 10%) was not significant (P>0.05). Boys were more
      active than girls by 17 to 21% (P < or =.01) at both baseline and follow-up.
      CONCLUSIONS: Despite the trend for greater physical activity at three of four
      study sites, and an overall difference of approximately 10% between intervention
      and control schools, high variability in accelerometer AVM and the opportunity to
      measure physical activity on only 1 day resulted in a the failure to detect the
      difference as significant.

PMID- 14636811
TI  - The impact of the Pathways intervention on psychosocial variables related to diet
      and physical activity in American Indian schoolchildren.
AB  - BACKGROUND: The purpose of this study was to examine the impact of the Pathways
      intervention on pychosocial variables related to physical activity and diet in
      American Indian children. METHODS: Schools serving American Indian children were
      randomized to a multicomponent intervention or control condition. At baseline
      (fall of third grade) and in the spring semester of third, fourth, and fifth
      grades 755 boys and 692 girls completed a classroom-administered questionnaire.
      The questionnaire assessed self-efficacy, knowledge, and behavioral intentions
      related to diet and physical activity, as well as weight loss behaviors and body
      image. RESULTS: Knowledge of nutrition and physical activity messages increased
      in both boys and girls in the intervention group compared to controls; however,
      knowledge of which foods contained more fat did not increase consistently.
      Compared to controls, self-efficacy to be physically active increased among girls
      in intervention schools, but not among boys, whereas self-efficacy to make more
      healthy food choices did not increase more than in controls in either gender. In
      the intervention group, compared to controls, healthy food intentions and
      participation in physically active behaviors increased in both boys and girls.
      Perception of healthy body size and weight loss attempts did not differ in the
      intervention and control groups. CONCLUSION: The Pathways intervention program
      had a positive impact on several aspects of obesity-related knowledge, attitudes,
      and behaviors.

PMID- 14636812
TI  - Pathways process evaluation results: a school-based prevention trial to promote
      healthful diet and physical activity in American Indian third, fourth, and fifth
      grade students.
AB  - BACKGROUND: Pathways was a large-scale, multisite, 3-year, study testing a school
      based intervention designed to lower percent body fat in American Indian
      children. METHODS: At the 21 intervention schools process evaluation data were
      collected for training of school personnel; implementation of the classroom and
      physical activity curricula; implementation of the project's food service
      guidelines in the school cafeterias; adult participation in the family events;
      and, students' perceived exposure to the Pathways interventions. RESULTS:
      Students received about 93% of the classroom curriculum lessons. The minimum
      requirement of physical education being taught three times per week for at least
      30 minutes duration was achieved by the fifth grade. The implementation of the
      food service behavioral guidelines increased from 51% in the third grade to 87%
      in the fifth grade. The family events had lower than anticipated adult
      participation. The participation rates were 45% during the third grade, and 41
      and 63% during the fourth and fifth grades, respectively. There was a significant
      difference between intervention and control students' perceived exposure to
      Pathways type interventions. CONCLUSION: The Pathways interventions were
      successfully implemented with good reach, high extent, and fidelity.

PMID- 14636813
TI  - Indices of changes in adiposity in American Indian children.
AB  - BACKGROUND: Pathways, a randomized trial, evaluated the effectiveness of a school
      based obesity prevention program on body composition changes in American Indian
      children. Several body composition methods were compared in intervention and
      control schools for assessing body composition changes. METHODS: Body composition
      methods, including skinfolds, bioelectric impedance analysis (BIA), body mass
      index (BMI), and using a combination of body composition methods were selected to
      assess 3-year changes in PBF in 705 children within 21 intervention schools and
      663 children within 20 control schools. The study equation using skinfolds, BIA,
      and BMI was developed on a previous sample of American Indian children using
      deuterium oxide dilution as the criterion method. RESULTS: Body fat changes among
      methods for the intervention sample ranged from 5.4% (BMI method) to 7.1%
      (combination of methods) and for the control sample, from 5.8% (BMI method) to
      7.3% (combination of methods). The study equation estimates were significantly
      higher than the other methods and the BMI equation estimates were significantly
      lower than the other methods except by BIA. The BIA equation showed a
      significantly larger standard deviation of the difference over the 3-year
      intervention than each of the other methods indicating less reliability for
      detecting body composition changes. CONCLUSIONS: Within the Pathways large scale
      intervention trial with American Indian children, we found comparable yet
      significantly different mean PBF changes among methods. However, BIA was not as
      reliable as skinfolds and the combination of BIA, skinfolds, and body weight in
      assessing PBF changes.

PMID- 14636814
TI  - School climate and implementation of the Pathways study.
AB  - BACKGROUND: Pathways was a multisite school-based study to prevent obesity in
      American Indian school children by encouraging healthy eating and physical
      activity. METHODS: Over the 3-year study, a total of 290 in-depth interviews were
      conducted with school administrators, food service managers, classroom teachers,
      and physical education instructors in all 21 intervention schools to examine
      support and barriers for Pathways. Analysis included qualitative assessment of
      key themes using NUD*IST and quantitative modeling of the impact of a school
      climate score on implementation of intervention components. RESULTS: Overall,
      teachers, food service managers, and physical education instructors were
      supportive of the Pathways interventions. School administration and lack of
      family participation were perceived barriers at some schools. Attitudes toward
      the program ranged from neutral to positive during the first year, with about two
      thirds giving positive ratings, with greater variation in successive years.
      Overall, the mean score was 3.5 on a 5-point scale (1=very negative, 5=very
      positive). School climate score was positively associated with classroom
      curriculum and student exposure indices, but not with family attendance, food
      service, or physical activity implementation indices. The latter two indices were
      associated with site. CONCLUSIONS: An assessment of school climate through
      interviews is useful in understanding successes and failures in a school-based
      health intervention and can predict implementation success for some programs.

PMID- 14636815
TI  - Pathways: lessons learned and future directions for school-based interventions
      among American Indians.
AB  - BACKGROUND: Pathways, a multicenter study to test the effect of a school-based
      program to prevent obesity in American Indian children, yielded many benefits and
      encountered many challenges. This paper explores what we have learned from this
      study and examines possible future directions. METHODS: Information presented in
      this paper is based on formative research, study results, and discussions with
      staff and investigators. RESULTS: Some of the lessons learned relate to having a
      strong relationship with the tribes, how best to engage the communities, the
      importance of formative research and achieving standardization in culturally
      diverse settings, how to incorporate cultural information into curricula, and the
      importance of family involvement. One of the strengths of the study was the
      collaborative process that teamed American Indian and non-American Indian
      investigators and staff. Researchers recognized that they must work in
      cooperation with research participants including their schools and communities to
      address challenges, to ensure accurate findings and analyses, and to share
      benefits. CONCLUSIONS: The lessons learned from Pathways offer valuable insights
      for researchers into successful approaches to the challenges inherent in research
      in American Indian communities, particularly in schools, and how to maximize the
      benefits of such a study.

PMID- 14636816
TI  - Toward the development of a motivational model of pain self-management.
AB  - Adaptive management of chronic pain depends to a large degree on how patients
      choose to cope with pain and its impact. Consequently, patient motivation is an
      important factor in determining how well patients learn to manage pain. However,
      the role of patient motivation in altering coping behavior and maintaining those
      changes is seldom discussed, and theoretically based research on motivation for
      pain treatment is lacking. This article reviews theories that have a direct
      application to understanding motivational issues in pain coping and presents a
      preliminary motivational model of pain self-management. The implications of this
      model for enhancing engagement in and adherence to chronic pain treatment
      programs are then discussed. The article ends with a call for research to better
      understand motivation as it applies to chronic pain self-management. In
      particular, there is a need to determine whether (and which) motivation
      enhancement interventions increase active participation in self-management
      treatment programs for chronic pain.

PMID- 14636817
TI  - Beneficial actions of neurotrophin treatment on diabetes-induced hypoalgesia in
      mice.
AB  - Studies were carried out in streptozotocin-treated diabetic mice to evaluate
      their behavioral responses to different noxious stimuli. In opposition to rats,
      streptozotocin-injected diabetic mice display a persistent hypoalgesia to non
      noxious mechanical stimulation (von Frey monofilament). Similarly, nocifensive
      responses of diabetic mice to formalin injection were significantly reduced in
      both acute and inflammatory phases. However, no overt differences were detected
      between nondiabetic and diabetic mice in their sensitivity to noxious heat
      (radiant heat), cold (acetone), or noxious mechanical (pinprick) stimuli applied
      to the hind paw. To evaluate whether neurotrophin treatment could normalize the
      sensory deficits, nerve growth factor (NGF) or glial cell line-derived
      neurotrophic factor (GDNF) was administered intrathecally to diabetic mice for 3
      weeks. Neurotrophin-treated mice were also compared to mice that received insulin
      for 3 weeks. Both NGF and insulin treatment significantly restored mechanical and
      chemogenic behavioral responses of diabetic mice. In contrast, GDNF treatment
      only reversed behavioral responses to chemogenic stimuli during the acute phase
      of the formalin test. These results demonstrate that diabetic mice develop
      reduced sensitivity to mechanical and chemical stimuli. Furthermore, these
      studies show that dorsal root ganglion neurons in diabetic mice are responsive to
      treatment with either NGF or GDNF; however, these 2 neurotrophins differ in their
      ability to affect distinct somatosensations.

PMID- 14636818
TI  - The influence of gender and race on physicians' pain management decisions.
AB  - This study set out to examine whether gender or race influences physicians' pain
      management decisions in a national sample of 712 (414 men, 272 women) practicing
      physicians. Medical vignettes were used to vary patient gender and race
      experimentally while holding symptom presentation constant. Treatment decisions
      were assessed by calculating maximum permitted doses of narcotic analgesic
      (hydrocodone) prescribed for initial pain treatment and for follow-up care. No
      overall differences by patient gender or race were found in decisions to treat or
      in maximum permitted doses. However, for persistent back pain, female physicians
      prescribed lower doses of hydrocodone, especially to male patients. For renal
      colic, lower doses were prescribed to black versus white patients when the
      patient was female, whereas the reverse was true when patients were male. These
      findings challenge a fairly extensive literature suggesting that physicians treat
      women and minorities less aggressively for their pain, and results offer further
      evidence that pain treatment decisions are influenced physician gender.

PMID- 14636819
TI  - Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted
      humans: a preliminary study.
AB  - Hyperalgesia has been demonstrated to be a cardinal sign of physical withdrawal
      from opioids in preclinical models for more than 30 years, although few empirical
      data exist to support its occurrence in humans. In this preliminary study we used
      the acute opioid physical dependence (APD) model to test for the presence of
      hyperalgesia to experimental cold-pressor pain in 4 healthy non-opioid-dependent
      men via 3 different pretreatment opioid administration protocols previously
      demonstrated to induce APD (morphine 18 mg/70 kg intramuscular, morphine 10 mg/70
      kg intravenous, hydromorphone 2 mg/70 kg intravenous), repeated on 2 separate
      occasions, and placebo. Cold-pressor pain threshold and tolerance were examined
      before opioid administration and 5 and 15 minutes after precipitated withdrawal
      with naloxone 10 mg/70 kg intravenous. Paired t tests comparing change scores
      between the opioid pretreatments and placebo showed that pain threshold and
      tolerance to the cold-pressor uniformly decreased across all APD induction
      methods, and the effect size was large (approximately 70% of baseline) and
      reproducible. These findings provide initial support for the existence of opioid
      induced hyperalgesia, which has been conceptualized as a coexisting opponent
      process to opioid-induced analgesia and proposed to be an alternative explanation
      for the development of analgesic tolerance to opioids.

PMID- 14636820
TI  - Stress influences the level of negative affectivity after forehead cold pressor
      pain.
AB  - The purpose of this study was to investigate simultaneously a stress manipulation
      and an experimental pain manipulation to determine how stress and pain interact
      to influence negative affectivity. One hundred healthy subjects completed a
      counterbalanced repeated measure crossover design in which stress (speech task)
      versus a nonstress control condition (magazine reading) was manipulated. Each
      session was immediately followed by a 2-minute forehead cold pressor task.
      Measures of affectivity (Positive Affect Negative Affect Schedule), pain ratings,
      cardiovascular measures (systolic blood pressure, diastolic blood pressure, heart
      rate), and salivary cortisol were obtained during each session. Regression
      analysis showed that the stress manipulation influenced the level of anger and
      that change in anger predicted post-pain negative affectivity independently of
      the contribution of maximum pain (model R(2) =.31), with 45% of the total model
      variance accounted for by change in anger and 17% of the total model variance
      accounted for by maximum pain intensity. In the nonstress condition only level of
      pain intensity was an independent predictor of negative affectivity (model R(2)
      =.16), with 69% of the total model variance accounted for by maximum pain
      intensity. These results show that stress significantly amplifies post-pain
      negative mood beyond that accounted for by the level of pain intensity alone.

PMID- 14636821
TI  - The effect of vagus nerve stimulation on migraines.
AB  - Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might
      reduce pain in patients with VNS device implanted for intractable seizures. One
      case report described possible benefits on migraines. We contacted all patients
      who received VNS therapy for intractable epilepsy between 1993 and 1999 at
      Southern Illinois University, Springfield, Illinois. Patients who had concomitant
      chronic pain were subsequently interviewed. Pain intensity before and after VNS
      implantation was rated by the patient as average, worst, and least and on numeric
      rating scale from 1 to 10. Current pain measurements were compared to
      preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who
      received VNS, 27 patients were interviewed; 4 patients had common migraine, and
      no other chronic pain syndromes were identified. All patients with migraine
      reported reductions in headache frequency and numeric rating scale score for
      average and least headache intensity. One patient reported complete relief of
      headaches. Improvement was reported to start 1 to 3 months after initiation of
      therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain
      relief, 2 reported a lot of pain relief, and 1 reported slight pain relief.
      Concomitant antiepileptic drugs were decreased in 3 patients and slightly
      increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

PMID- 14636822
TI  - The immunopharmacology of paclitaxel (Taxol), docetaxel (Taxotere), and related
      agents.
AB  - Paclitaxel (Taxol) and docetaxel (Taxotere) are among the most unique, and
      successful, chemotherapeutic agents used for the treatment of breast and ovarian
      cancer. Both agents have anti-mitotic properties derived from binding to tubulin
      and excessive stabilization of microtubules. Their anti-neoplastic effects derive
      from this mechanism. Distinct from their effects on microtubule stabilization,
      paclitaxel, docetaxel, and related taxanes display immunopharmacological traits.
      In this review, we discuss their induction of pro-inflammatory genes and
      proteins; the current hypotheses on the molecular mechanism for this induction,
      especially its relationship to the lipopolysaccharide (LPS) signaling pathway. We
      also discuss the structure-activity relationships (SAR) that govern gene
      induction, especially the striking differences between the SAR for murine and
      human cells in vitro. Lastly, we discuss the immunopharmacological traits of
      paclitaxel and docetaxel in terms of their relevance to human clinical
      pharmacology and toxicology and their activity in animal models of autoimmune
      disorders.

PMID- 14636823
TI  - Laser scanning confocal fluorescence microscopy: an overview.
AB  - Innovative and important aspects of laser scanning confocal fluorescence imaging
      (LSCFI) are presented here as a general overview. We have described and discussed
      the technology of the procedure in some detail. We also report some of our
      original work with transmembranous uptake of 5S gamma-globulin on living human
      leukocytes as an example of one specific application of LSCFI. These original
      data and results are presented, as well as citing other uses and applications, to
      show the power of LSCFI technique. The article will hopefully be useful for those
      not familiar with the methodology and utility of laser scanning confocal
      fluorescence microscopy. Applications of LSCFI are very diverse, and there are
      new applications of this technology constantly being developed. Interest is
      growing in LSCFI, particularly in the pharmacologic and therapeutic areas, as
      demonstrated in this article.

PMID- 14636824
TI  - A new flavonoid derivative, dosmalfate, attenuates the development of dextran
      sulphate sodium-induced colitis in mice.
AB  - In this study, we have evaluated the efficacy of dosmalfate, a new flavonoid
      derivative compound, for the prevention and treatment of experimental colitis. To
      induce colitis, BALB/c mice received 5% dextran sulphate sodium (DSS) in their
      drinking water continuously for 7 days. Colitis was quantified by a clinical
      damage score, colon length, weight loss, stool consistency and rectal bleeding.
      Inflammatory response was assessed by neutrophil infiltration, determined by
      histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1 beta,
      prostaglandins (PG)E(2) and (PG)D(2) concentrations in colonic tissue,
      histological and histochemical analysis of the lesions were also measured.
      Dosmalfate (400-800 mg/kg body weight, p.o.) ameliorated severe colitis reduced
      the degree of inflammation through reduction of neutrophil infiltration and IL-1
      beta levels. (PG)E(2) and (PG)D(2) synthesis were significantly reduced in
      colitis control group and treatment with dosmalfate abolished the decrease in PG
      synthesis in colon mucosa. We conclude that dosmalfate is protective in acute DSS
      induced colitis. The beneficial effects seem to be related to a decrease of
      neutrophil infiltration, absence of up-regulation of IL-1 beta and increase of PG
      production in colon mucosa.

PMID- 14636825
TI  - Differing effects of two iron compounds on experimental arthritis, TNF-alpha
      levels and immune response in mice.
AB  - The effects of ferric-sorbitol-citrate and ferric-citrate on the severity of
      experimental arthritis, TNF-alpha secretion and the immune status were examined
      in mice. Arthritis was induced by footpad injection of methylated BSA and
      intraperitoneal injection of Bordetella pertussis. Joint and footpad swelling
      were measured weekly by a caliper. TNF-alpha serum levels were measured by ELISA.
      The immune status was determined by the response of mouse lymphocytes to ConA in
      vitro and by the antigen-presenting cell assay. Experimental arthritis was
      aggravated by ferric-citrate, whereas ferric-sorbitol-citrate did not promote it.
      If applied to normal (non-arthritic) mice three times a week for 4 weeks, ferric
      sorbitol-citrate stimulated isolated splenocytes to increase production of TNF
      alpha, the function of antigen-presenting cells and lymphocyte proliferation in
      response to ConA in vitro. TNF-alpha production by cultured splenocytes was also
      stimulated. In mice with antigen-induced arthritis, iron compounds did not
      additionally stimulate TNF-alpha production. Thus, we have shown that ferric
      sorbitol-citrate stimulated TNF-alpha production, antigen-presenting cell
      activity and cellular immune response. Development of antigen-induced arthritis
      and TNF-alpha production in arthritic mice were not stimulated.

PMID- 14636826
TI  - Calphostin C as a rapid and strong inducer of apoptosis in human coronary artery
      smooth muscle cells.
AB  - Vascular smooth muscle cells (VSMCs) play a major role in the development of
      atherosclerotic and restenotic lesions. The apoptotic process has been implicated
      in the development of this pathology. In this study, we characterized the
      induction of apoptosis by calphostin C (CC), a protein kinase C (PKC) inhibitor,
      in primary human coronary artery smooth muscle cells in the presence and absence
      of insulin-like growth factor-I (IGF-I). Additionally, we investigated the signal
      transduction pathways important for IGF-I mediated protection. Calphostin C
      induced apoptosis, as measured by terminal deoxy-UTP nick-end labeling (TUNEL),
      in a time- and dose-dependent manner, approaching 20% within 6 h of 50 nM
      calphostin C treatment. The amount of apoptosis increased to 44.58+/-8.08%,
      47.54+/-1.66% and 78.1+/-11.9% after 8, 10 and 12 h of treatment, respectively
      (p<0.01 vs. control). IGF-I offered significant protection (p<0.05) at 8 and 10 h
      of treatment (60.6% and 52.5% protection, respectively). DNA ELISA confirmed the
      apoptotic effect of calphostin C and the protective effect of IGF-I. After 6 h of
      calphostin C treatment, DNA ELISA revealed 11.20+/-1.53 fold greater apoptosis as
      compared to baseline values. IGF-I treatment offered a level of protection of
      46.6% as measured by DNA ELISA (p=0.06). Apoptosis was further qualitatively
      confirmed by time-lapse video microscopy and scanning electron microscopy.
      Interestingly, inhibitors of phosphatidylinositol-3-kinase (PI-3-K), p38 and
      extracellular regulated kinase (ERK) activation significantly (p<0.05 vs.
      calphostin C only treatment) increased apoptosis when used in conjunction with
      calphostin C. Inhibitors of phospatidylinositol-3-kinase and ERK activation
      reversed IGF-I protection. However, the p38 inhibitor SB203580 failed to reverse
      IGF-I protection. This study characterized an apoptotic system for human coronary
      artery smooth muscle cells offering a rapid and strong induction of programmed
      cell death (PCD) that remains responsive to the survival effects of IGF-I.
      Studies utilizing this system may prove useful in understanding the apoptotic
      response of VSMCs in the arterial wall.

PMID- 14636827
TI  - Concentration-dependent bifunctional effect of TGF-beta 1 on immunoglobulin
      production: a role for Smad3 in IgA production in vitro.
AB  - Injury to the liver results in rapid induction of transforming growth factor
      beta1 (TGF-beta(1)) consistent with a role for TGF-beta(1) in repairing damaged
      tissue. In addition to its ubiquitous role in injury repair, TGF-beta(1) is also
      well established as a critical regulator of immune homeostasis; however, its
      mechanisms of action remain enigmatic. We have previously demonstrated that the
      hepatotoxic chlorinated hydrocarbon, carbon tetrachloride, suppresses helper T
      lymphocyte function in a TGF-beta(1)-dependent manner. Here, we report that, in
      opposition to its immunosuppressive effects at picomolar concentrations,
      femtomolar concentrations of TGF-beta(1) augment T cell-dependent anti-sRBC IgM
      antibody forming cell (AFC) and T cell-independent DNP-Ficoll-induced AFC
      responses. These data support a concentration-dependent bifunctional effect by
      TGF-beta(1) on humoral immune responses in vitro. We further investigated a
      putative mechanistic role for Smad3, an intracellular mediator of TGF-beta(1)
      signaling, in propagating the inhibitory effects of TGF-beta(1) on humoral immune
      responses. Relative to wild type littermates, splenocytes from mice homologous
      for a null mutation in the gene encoding the TGF-beta receptor-activated Smad3
      (Smad3(Exon8-/-)) were less sensitive to inhibition by TGF-beta(1) following anti
      sRBC- and LPS-sensitization in vitro. In agreement, inhibition of IgM protein
      production by TGF-beta(1) was also dampened in LPS-sensitized Smad3(Exon8-/-)
      splenic B cells. Moreover, stimulation of IgA by TGF-beta(1) was abrogated in LPS
      sensitized Smad3(Exon8-/-) splenocytes suggesting an additional role for Smad3 in
      regulating IgA production in vitro. Our results suggest that the effects of TGF
      beta(1) on humoral immune responses fundamentally differ in a concentration
      dependent manner and are mediated, in part, through Smad3 signaling.

PMID- 14636828
TI  - Membrane lipid microdomains differentially regulate intracellular signaling
      events in human neutrophils.
AB  - The integrity of lipid microdomains is disrupted after cell treatment with
      cholesterol-depleting reagents, such as methyl-beta-cyclodextrin (MCD). We
      investigated the roles of lipid microdomains in the regulation of intracellular
      signaling events and functional responses in isolated human neutrophils.
      Treatment of neutrophils with MCD caused inhibition of intracellular calcium
      increase evoked by interleukin-8 (IL-8) or low concentrations of formyl-Met-Leu
      Phe (fMLP). No significant decrease of the initial peak of the calcium response
      was measured when neutrophils were stimulated with 100 nM or higher
      concentrations of fMLP. MCD inhibited the phosphorylation of extracellular signal
      regulated kinase (Erk) induced by IL-8 or lower concentrations of fMLP. However,
      Erk phosphorylation evoked by higher concentrations of fMLP was only slightly
      affected. MCD treatment increased phosphorylation of p38 MAP kinase and caused
      strong up-regulation of both CD11b and CD66b in resting neutrophils. Cholesterol
      depletion greatly inhibited IL-8-induced elastase release but had little effect
      of fMLP-induced degranulation. Our study brings evidence suggesting that lipid
      microdomains are critically required for the signaling events triggered by IL-8.
      Calcium mobilization and elastase release induced by WKYMVM, a selective agonist
      for formyl peptide receptor-like 1 (FPRL1), were significantly inhibited by MCD,
      suggesting that the resistance of fMLP-mediated responses to MCD is not related
      to the partition of receptor subtypes to lipid microdomains. It is more probable
      that cholesterol depletion interferes with the ability of different G proteins to
      couple to their corresponding receptors and this might account for the
      differential effects of MCD treatment on chemoattractant-induced effects in human
      neutrophils.

PMID- 14636829
TI  - Apoptosis-mediated selective killing of malignant cells by cardiac steroids:
      maintenance of cytotoxicity and loss of cardiac activity of chemically modified
      derivatives.
AB  - Cardiac glycosides are commonly used drugs in clinical medicine. We analyzed the
      cytotoxic effect of six steroids belonging to the bufadienolide family on
      malignant T lymphoblasts and normal peripheral blood mononuclear cells (PBMC).
      One compound was a natural bufadienolide glycoside (hellebrin) with cardiac
      activity. The other five compounds were chemically modified derivatives that did
      not contain cardioactive groups. We found that these steroids were able to cause
      time-dependent apoptosis in Jurkat T lymphoblasts, whereas they only minimally
      affected PBMC. Preferential killing of malignant cells was induced by the natural
      cardioactive substance hellebrin and by three of the five chemically modified non
      cardioactive derivatives. The substances caused mitochondrial transmembrane
      potential disruption and internucleosomal DNA fragmentation in tumor cells. The
      cytoplasmic and nuclear events of bufadienolide-induced apoptosis were strongly
      inhibited in the presence of caspase 8, caspase 9, or caspase 3 inhibitors, as
      well as in the presence of the broad-spectrum caspase inhibitor Z-VAD-FMK.
      Overexpression of Bcl-2 significantly protected bufadienolide-treated cells from
      phosphatidylserine translocation, transmembrane potential disruption, and
      internucleosomal DNA fragmentation. Our results show that the analyzed
      bufadienolide derivatives preferentially kill malignant human lymphoblasts by
      initiating apoptosis via the classical caspase-dependent pathway. Apoptosis
      inducing agents specific for tumor cells might be ideal anti-tumor drugs. The
      therapeutic use of bufadienolides has been hampered by their concomitant cardiac
      activity. The description of compounds without cardiac activity but with tumor
      specific cytotoxicity suggests the potential of using them in cancer therapy.

PMID- 14636830
TI  - Receptor density dictates the behavior of a subset of steroid ligands in
      glucocorticoid receptor-mediated transrepression.
AB  - By co-expressing glucocorticoid receptor (GR) and transcriptional reporter
      systems in GR-deficient Cos-7 cells, we profiled potency and efficacy of a panel
      of GR ligands as a function of GR expression levels (density). Our results show
      that potency and efficacy for GR full agonists, such as dexamethasone, in these
      transrepression assays are affected by receptor density. Intriguingly, receptor
      density dramatically influenced the behavior of the GR antagonist RU486 or the GR
      agonist medroxyprogesterone acetate (MPA). At high receptor density, both MPA and
      RU486 behaved as full agonists in transrepression: reducing GR density, however,
      resulted in conversion of these ligands from full agonist to full antagonists. In
      contrast, varying GR density could not convert cortisol and budesonide from GR
      agonists to antagonists. These results have clearly demonstrated, for the first
      time, an effect of receptor density on the agonist and antagonist properties of
      RU486 and MPA in GR-mediated transrepression.

PMID- 14636831
TI  - Effect of endosulfan and malathion on lipid peroxidation, nitrite and TNF-alpha
      release by rat peritoneal macrophages.
AB  - Endosulfan and malathion are organochlorine and organophosphate insecticides,
      respectively. The toxicity of both the insecticides are well known on non-target
      organisms. Both endosulfan and malathion are reported to suppress humoral as well
      as cellular immune responses. We investigated the possible effect of both these
      insecticides on lipid peroxidation, nitrite production and TNF-alpha generation
      in rat peritoneal macrophages under in vitro conditions. Rat peritoneal cells
      were collected and cultured with or without insecticides and relevant stimulants
      for lipid peroxidation, generation of nitric oxide and TNF-alpha. FeSO(4) was
      used as an inducer for lipid peroxidation and LPS was used to induce nitric oxide
      synthase and release of TNF-alpha. Lipid peroxidation was assayed by estimating
      MDA; nitric oxide was determined by estimating nitrite and TNF-alpha by using an
      assay kit in culture supernatants. Both endosulfan and malathion had no effect on
      lipid peroxidation. Endosulfan did not have any influence on nitrite production,
      but suppressed the LPS-induced TNF-alpha generation. Malathion, however, showed a
      direct suppression on nitrite production and suppression of LPS-induced TNF-alpha
      generation. This study suggests that functional aberrations of macrophages may
      contribute significantly to the immunomodulation reported for these insecticides.

PMID- 14636832
TI  - Differential inhibition of receptor activation by two mouse monoclonal antibodies
      specific for the human leukotriene B4 receptor, BLT1.
AB  - The inflammatory mediator leukotriene B(4) (LTB(4)) binds to and activates a G
      protein-coupled receptor named BLT(1). We have previously produced two monoclonal
      antibodies, named 7B1 and 14F11, that bind specifically to this receptor. Using a
      HeLa cell line expressing human BLT(1), we find that both antibodies inhibit
      LTB(4)-induced calcium release, and activation of a MAP-kinase-sensitive
      luciferase reporter system. The normal chemotactic movement of polymorphonuclear
      cells towards higher LTB(4) concentrations was also strongly inhibited by both
      antibodies. Neither antibody was found to activate BLT(1), and experiments using
      cyclic peptide fragments of the BLT(1) n-terminal and extracellular loops showed
      that these antibodies bind only to complex epitopes in the tertiary, membrane
      bound, conformation of the receptor protein. In ligand binding experiments, 7B1
      was found to be a competitive antagonist, while 14F11 was a noncompetitive
      antagonist that inhibited receptor activation, but not agonist (LTB(4)) binding.
      14F11 will be a useful tool for studying the mechanisms of receptor activation.

PMID- 14636833
TI  - Polyphenolic antioxidants inhibit peptide presentation by antigen-presenting
      cells.
AB  - Antigen-presenting cells (APC) provide two essential signals, e.g., antigenic
      peptides as well as costimulatory molecules for T-cell activation. Small
      molecules of smoke tobacco extracts (SM-STE) inhibited antigen presentation of
      A20 to OVAp-specific T-cell hybridomas. Pretreatment of A20 but not T hybridomas
      abrogates the APC function. Viability of APC and levels of MHCII, CD40 and B7 of
      APC were not affected by this treatment. The active principle, inhibiting APC was
      reproduced with pure tobacco polyphenols, quercetin and its glycoside, rutin.
      Antioxidant activity of rutin is relevant since rutin downregulated levels of
      reactive oxygen species (ROS) in phorbol ester-stimulated A20; moreover, another
      antioxidant, N-acetyl cysteine (NAC) also inhibited antigen presentation, albeit
      at a higher concentration. Other types of APC, such as bone marrow-derived mast
      cells (BMMC), MHCII-transfected fibroblast, and splenocytes are affected by
      tobacco polyphenols. We propose that polyphenols may affect redox-sensitive
      signal transduction pathway since APC function of PD 98059, MEK inhibitor
      pretreated A20 were similarly abrogated. Taken together, we propose that
      maintaining appropriate intracellular redox of APC is crucial for its antigen
      presenting function.

PMID- 14636834
TI  - In vivo modulation of the circulating lymphocyte subsets and monocytes by
      androgen.
AB  - Androgens influence some immunological processes, including alternation of the
      number and function of the circulating lymphocytes and monocytes. In the present
      study, the effects of three different doses of testosterone on the numbers and
      percentages of the peripheral blood cells were investigated; the lymphocyte
      subsets were determined and the proliferation of lymphocyte was detected. Groups
      of Sprague-Dawley rats were treated with 0.5, 2.5, 12.5 mg/kg or only vehicle,
      respectively. Compared with controls, the results of complete blood counts showed
      that the absolute and relative numbers of monocytes decreased. The lymphocyte
      subpopulations determined by flow cytometry indicated an increase in CD8+ T
      cells, whereas the CD3+, CD4+ and CD4+CD8+ T cells remained unchanged. Thus, the
      immunoregulatory index (CD4+/CD8+ ratio) decreased. The proliferative activities
      determined by MTT assay were down-regulated. In conclusion, the immunosuppressive
      effects of testosterone may be attributed to a decline in number of monocytes,
      CD4+/CD8+ ratio and proliferative activities together with an increase of CD8+ T
      cells in Sprague-Dawley rats.

PMID- 14636835
TI  - The beta-(1-->6)-branched beta-(1-->3) glucohexaose and its analogues containing
      an alpha-(1-->3)-linked bond have similar stimulatory effects on the mouse spleen
      as Lentinan.
AB  - The stimulatory effects of the synthetic beta-(1-->6)-branched beta-(1-->3)
      glucohexaose and its analogues containing an alpha-(1-->3)-linked bond on the
      mouse spleen were studied for elucidation of the mechanism of their antitumor
      activity, and their stimulatory effects were compared with Lentinan. The mouse
      spleen's weight was increased after the intraperitoneal (i.p.) injection of the
      oligosaccharides compared with the saline group. In addition, routinely
      hematoxylin and eosin (HE)-stained spleen sections showed that the injection also
      changed the spleen's histopathology. RNA samples were isolated from splenocytes
      of oligosaccharides, Lentinan or saline-injected mice. Reverse transcription
      polymerase chain reaction (RT-PCR) and Northern blot showed that the
      administration of the oligosaccharides or Lentinan enhanced mouse spleen mRNA
      production of TNF-alpha but not IL-2. The injection also enhanced Concanavalin A
      (Con A)-induced mouse splenocytes proliferation, but the in vitro administration
      of the oligosaccharides did not have the proliferation-enhancing effect. Taken
      together, these results suggest that the synthetic beta-(1-->6)-branched beta-(1-
      >3) glucohexaose and its analogues containing an alpha-(1-->3)-linked bond have
      similar stimulatory effects as Lentinan. Additionally, they may exert their
      antitumor effects through the induction of splenocytes mediated immune responses.

PMID- 14636836
TI  - Toll-like receptor 4-dependent activation of macrophages by polysaccharide
      isolated from the radix of Platycodon grandiflorum.
AB  - Platycodon grandiflorum, a traditional oriental herbal medicine, is known to have
      immunostimulatory and antitumor effects. PG, a polysaccharide isolated from P.
      grandiflorum, has been reported to activate macrophages and B cells. Here, we
      investigated the membrane receptor and intracellular signaling responsible for
      the activation of macrophages by PG. PG induced the production of nitric oxide
      (NO) and the mRNA expression of iNOS in RAW 264.7 cells. To investigate the
      membrane receptor involved in the activation of NO production, we examined the
      effect of PG on the production of NO in mouse peritoneal macrophages isolated
      from wild type C3H/HeN and functional Toll-like receptor 4 (TLR4)-deficient
      C3H/HeJ mice. PG induced NO production by macrophages isolated from C3H/HeN mice,
      but had no effect on NO production by macrophages isolated from C3H/HeJ mice.
      Moreover, monoclonal antibodies directed to TLR4 blocked PG-mediated induction of
      NO production. In addition, LBP and sCD14 was also found to be involved in the
      activation of NO production by PG. To further investigate, we examined the effect
      of PG on the activation of DNA binding of NF-kappa B, which is a downstream
      transcriptional regulator of TLR4. PG caused degradation of I kappa B and
      activation of DNA binding of NF-kappa B. In addition, TPCK, a specific NF-kappa B
      inhibitor, abolished PG-mediated induction of DNA binding of NF-kappa B,
      production of NO and mRNA expression of iNOS, demonstrating the involvement of NF
      kappa B in PG-mediated macrophage activation. Taken together, these results
      suggest that PG-mediated induction of NO production and iNOS mRNA expression in
      macrophages is mediated, at least in part, by TLR4/NF-kappa B signaling pathway.

PMID- 14636837
TI  - Neuropeptides (SP and CGRP) augment pro-inflammatory cytokine production in HSV
      infected macrophages.
AB  - Neuropeptides are able to modulate cytokine production by macrophages in response
      to various stimulators. In this study, the effects of neuropeptides substance P
      (SP) and calcitonin gene-related peptide (CGRP) on production of pro-inflammatory
      cytokines TNF and IL-1 beta by macrophages were considered. Mouse peritoneal
      macrophages were infected with herpes simplex virus type-1 (HSV-1), or remained
      unstimulated, and cytokine assays were performed after 12 h. IL-1 beta and TNF
      secretion by unstimulated macrophages have been significantly increased in the
      presence of SP and CGRP. Each neuropeptide, alone or in coordination with the
      other, caused significant increase in IL-1 beta and TNF production by HSV
      infected mouse peritoneal macrophages. It was concluded that the macrophage
      mediated inflammatory response to HSV-1 is enhanced in the presence of these
      neuropeptides.

PMID- 14636838
TI  - An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity
      without inducing cell death.
AB  - Previous reports have demonstrated that extracts of the plant Uncaria tomentosa
      inhibit tumor cell proliferation and inflammatory responses. We have confirmed
      that C-Med 100, a hot water extract of this plant, inhibits tumor cell
      proliferation albeit with variable efficiency. We extend these findings by
      showing that this extract also inhibits proliferation of normal mouse T and B
      lymphocytes and that the inhibition is not caused by toxicity or by induction of
      apoptosis. Further, the extract did not interfere with IL-2 production nor IL-2
      receptor signaling. Since there was no discrete cell cycle block in C-Med 100
      treated cells, we propose that retarded cell cycle progression caused the
      inhibition of proliferation. Collectively, these data suggested interference with
      a common pathway controlling cell growth and cell cycle progression. Indeed, we
      provide direct evidence that C-Med 100 inhibits nuclear factor kappa B (NF-kappa
      B) activity and propose that this at least partially causes the inhibition of
      proliferation.

PMID- 14636839
TI  - Effects of tramadol on synovial fluid concentrations of substance P and
      interleukin-6 in patients with knee osteoarthritis: comparison with paracetamol.
AB  - Both the analgesic drugs tramadol and paracetamol are widely used for the
      symptomatic therapy of osteoarthritis (OA). The aim of this double-blind,
      randomised study in patients with knee OA was to compare their effects on
      synovial fluid concentrations of interleukin (IL)-6 and substance P (SP).
      Moreover, we evaluated plasma and synovial fluid concentrations of tramadol and
      its active metabolite (O-desmethyl-tramadol, M1) after oral treatment with this
      drug. Twenty patients were enrolled. A group of 10 patients received tramadol (50
      mg three times a day), and another group of 10 patients were treated with
      paracetamol (500 mg three times a day) for 7 days. Both drugs significantly
      reduced the intensity of joint pain. The synovial fluid concentrations of SP were
      significantly reduced only by the treatment with tramadol. In this group of
      patients, IL-6 synovial fluid concentrations were slightly, but not
      significantly, decreased. Paracetamol did not significantly change the synovial
      fluid concentrations of SP and IL-6. After oral administration, a considerable
      amount of tramadol was measurable in synovial fluid. Both in plasma and synovial
      fluid the concentrations of M1 were markedly lower than those of tramadol, with a
      T/M1 ratio of 14.7+/-4.6 and 9.3+/-3.9, respectively. These data demonstrate that
      the activity of tramadol may involve the modulation of inflammatory mediators.
      Moreover, they indicate that after oral treatment with tramadol, both the parent
      drug and its active metabolite can penetrate into synovial fluid.

PMID- 14636840
TI  - Leaky neural integration observed in square-wave jerks.
AB  - PURPOSE: To clarify the neuronal mechanism for the square-wave jerks (SWJs).
      METHODS: A 66-year-old man presented with oscillatory eye movements. He showed
      horizontal nystagmus in rightward gaze and SWJs during fixation at straight
      ahead. We recorded his eye movements with search coil methods and quantitatively
      analyzed them. RESULTS: Visually guided rightward saccades were followed by
      exponential drifts with average time constants of 0.3-1.0 second, indicating a
      leaky rightward velocity-to-position integrator. Amplitude of SWJs ranged from
      0.5 to 2.5 degrees and average intersaccadic interval was 0.2 seconds. In
      addition, exponential drifts similar to those observed after visually guided
      saccades were observed in the SWJs. Rightward fast eye movements of SWJs were
      followed by exponential drifts lasting for 0.2 seconds with average time constant
      (+/-SD) of 0.7+/-0.3 seconds. CONCLUSIONS: Position signals after visually guided
      saccades and SWJs were outputs of the identical velocity-to-position integrator.
      SWJs are generated by the neural circuits involving a pulse generator and a
      velocity-to-position integrator.

PMID- 14636841
TI  - Predicting glaucomatous sensitivity loss using perimetric color saturation test.
AB  - PURPOSE: To predict future glaucomatous sensitivity loss using a perimetric color
      saturation test (PCST) that measures the color saturation discrimination
      threshold for six hues (red, yellow, green, green-blue, blue, and purple) at 9
      degrees in horizontal and 3 degrees in vertical extrafoveal points. METHODS: This
      new test was carried out on 31 patients (31 eyes) with early glaucoma or ocular
      hypertension. The sensitivity loss at the four points approximately 9.5 degrees
      apart from the fixation point was prospectively evaluated annually for 3 years
      using the Humphrey Field Analyzer (HFA) program central 30-2. The initial results
      of PCST and the total deviation (TD) in the follow-up HFA results were compared.
      RESULTS: Twenty-seven patients (27 eyes) were followed up for 3 years. The color
      saturation threshold for six hues was correlated with the TD of HFA results at
      108 points in the 27 eyes. The TD was -4 dB or better at the baseline measurement
      in 91 out of the 108 points. The averaged TD in the second and the third year in
      the follow-up period decreased below -4 dB in 10 of these 91 points, which were
      categorized as progression points in relation to the 81 nonprogression points. In
      the initial PCST, only the saturation threshold for purple was higher in the
      progression points when compared with the nonprogression points (P=.0004, Mann
      Whitney U-test). CONCLUSION: Future sensitivity loss is most likely at the points
      where the threshold of color saturation discrimination is increased for purple in
      eyes with early glaucoma or ocular hypertension.

PMID- 14636842
TI  - Scanning laser polarimetry in patients with acute attack of primary angle
      closure.
AB  - PURPOSE: To compare the retinal nerve fiber layer measurements of attacked eyes
      with their fellow eyes after a single unilateral attack of acute primary angle
      closure (APAC). METHODS: Patients with a single episode of APAC in 1 eye,
      successfully treated with laser peripheral iridotomy, were recruited. Eyes with
      persistently raised intraocular pressure (IOP) after resolution of the acute
      attack were excluded. Scanning laser polarimetry was carried out at 6 months
      after remission of the acute attack. The various parameters between the attacked
      and the fellow eyes were compared using the Student t-test. RESULTS: Twenty-six
      patients (24 female and 2 male, mean age 66.9+/-8.1 years) were recruited. The
      duration of the APAC ranged from 5 to 98 hours (mean, 36.3 hours). The mean
      presenting IOP during the acute attack was 62.0+/-9.4 mm Hg. Only the mean
      inferior ratio and the ellipse modulation showed a statistically significant
      difference between the attacked and the fellow eyes among the 12 standard
      scanning laser polarimetry measurement parameters. CONCLUSION: No severe retinal
      nerve fiber layer damage was documented in eyes that suffered a single episode of
      APAC with duration of attack up to 48 hours. With duration of attack longer than
      48 hours, retinal nerve fiber layer damage was detected.

PMID- 14636843
TI  - Interleukin-8 expressed in the granulocytes of the eye in a patient with Behcet's
      disease complicated by lens-induced endophthalmitis.
AB  - BACKGROUND: Interleukin-8 (IL-8) is believed to be involved in the progression of
      intraocular inflammation. We sought the source of IL-8 in the enucleated eye of
      the present patient. CASE: A 40-year-old Japanese man was diagnosed as having
      Behcet's disease. His vision deteriorated due to persistent uveitis and secondary
      glaucoma. His left eye had lens-induced endophthalmitis. OBSERVATIONS: The left
      eye had to be enucleated, and it was investigated by an immunohistochemical
      analysis using antibodies for CD 1a (dendritic cells), CD 3 (T cells), CD 68
      (monocytes/macrophages), interferon-gamma, or IL-8. Fibrovascular tissue had
      formed on and beneath the lens where inflammatory cells had infiltrated. Most of
      the mononuclear inflammatory cells were T cells. A large number of macrophages
      were observed especially around the lens. Interferon-gamma-positive cells were
      scattered, while IL-8 was observed only in the accumulated granulocytes, but not
      in either mononuclear cells or macrophages. CONCLUSION: IL-8 is thus considered
      to play a role in the progression of intraocular inflammation, and granulocytes
      are thought to be a possible source of IL-8 in endophthalmitis.

PMID- 14636844
TI  - Alterations of fatty acid composition of erythrocyte membrane in type 2 diabetes
      patients with diabetic retinopathy.
AB  - PURPOSE: To investigate the relationship between the erythrocyte membrane fatty
      acid components and diabetic retinopathy in patients with type 2 diabetes
      mellitus. METHODS: The study was performed in 40 patients. Thirty of the 40 were
      type 2 diabetic patients classified into three groups according to Early
      Treatment Diabetic Retinopathy Study Group (ETDRS) criteria: 10 with mild
      moderate nonproliferative retinopathy (group 1), 10 with moderate-severe
      nonproliferative retinopathy (group 2), and 10 with proliferative retinopathy
      (group 3). Ten age- and sex-matched healthy nondiabetic individuals were selected
      as controls. We examined the fatty acid composition of the erythrocyte membrane
      by a gas chromatographic method. RESULTS: In patients with nonproliferative
      diabetic retinopathy, we found statistically significant decreases in palmitic
      and stearic acids, and statistically significant increases in oleic, linoleic,
      behenic, and lignoceric acids, while arachidic and arachidonic acids remained
      unchanged. Except for the increase in arachidic acid, the results were similar to
      those in the proliferative retinopathy patients. CONCLUSIONS: The fatty acid
      component of the erythrocyte membrane alters in type 2 diabetes mellitus.
      Prospective studies are needed to evaluate the relationship between the free
      fatty acid composition of erythrocytes and diabetic retinopathy.

PMID- 14636845
TI  - Expression of hyaluronan synthase in intraocular proliferative diseases:
      regulation of expression in human vascular endothelial cells by transforming
      growth factor-beta.
AB  - PURPOSE: To investigate the role of hyaluronan (HA) and elucidate the mechanisms
      that regulate the expression of hyaluronan-synthesizing enzymes in vascular
      endothelial cells (VECs) in intraocular proliferative diseases. METHODS: Cultured
      VECs were used. Hyaluronan synthase (HAS) expression was determined on the mRNA
      products obtained by reverse transcription polymerase chain reaction (RT-PCR).
      The effect of transforming growth factor-beta(1)(TGF-beta(1)) and/or platelet
      derived growth factor-BB (PDGF-BB) on HAS expression was examined by quantitative
      RT-PCR and Western blot analysis. HAS expression in intraocular proliferative
      membranes was observed by immunohistochemistry. RESULTS: Cultured VECs expressed
      the three HAS isoforms. Stimulation of VECs with TGF-beta(1) induced a marked
      increase in the expression level of HAS2 mRNA and protein. The stimulatory effect
      of PDGF-BB was less potent. A synergistic or additive effect between TGF-beta(1)
      and PDGF-BB-induced HA synthesis was not observed. Furthermore, HAS1 and HAS2
      exhibited differential expression in VECs and non-VECs populating intraocular
      proliferative membranes. CONCLUSIONS: The expression of each HAS isoform is
      regulated differently by growth factors and cytokines in VECs. Importantly, HA
      synthesizing enzymes were expressed in cells populating proliferative membranes
      obtained from eyes of patients with proliferative vitreoretinal diseases, and
      thus may be key molecules in the events that control progression of the
      proliferative diseases.

PMID- 14636846
TI  - Quantitative analysis of proliferation, apoptosis, and angiogenesis in
      retinoblastoma and their association with the clinicopathologic parameters.
AB  - PURPOSE: Quantitative analyses of proliferation, apoptosis, and angiogenesis,
      which may be important for the prognosis of retinoblastoma, were performed and
      possible associations with some well-known clinicopathologic parameters were
      investigated. METHODS: Fifty-three pathology specimens (43 enucleations, 10
      exenterations) were evaluated by immunohistochemical methods. The proliferative
      index was detected by Ki67 antibody staining. The apoptotic index was calculated
      by the in situ terminal deoxynucleotidyl transferase mediated dUTP nick end
      labeling (TUNEL) method, and angiogenesis was detected by CD34 antibody staining.
      RESULTS: The mean proliferative index was 37.63+/-11.12, the mean apoptotic index
      was 2.67+/-1.18, and the microvessel density and mean vascular area were
      determined as 3.14+/-1.4 and 38.73+/-12.70, respectively. Statistical analysis
      showed that the proliferative index was directly proportional to the tumor
      dimensions (P=.001). In addition, the tumor dimensions were larger in cases where
      the apoptotic index was below 2.4% (P=.011). In cases where the apoptotic index
      was over 2.4%, no metastasis was observed and also a lower proliferative index
      was found (P=.014). CONCLUSIONS: Proliferation appears to be more important than
      apoptosis and angiogenesis in determining the tumor dimensions. The apoptotic
      index may be an important predictor of metastasis, and may be useful in the
      follow-up of bilateral cases with 1 eye enucleated.

PMID- 14636847
TI  - Evaluation of the dynamics of choroidal circulation in experimental acute
      hypertensionusing indocyanine green-stained leukocytes.
AB  - PURPOSE: To evaluate the dynamics of choroidal circulation in experimental acute
      hypertension, using the indocyanine green leukocyte angiography (ILA) method,
      which the authors have developed for the evaluation of leukocyte dynamics in
      choroidal circulation. METHODS: Japan White rabbits were used in the present
      study. Leukocytes were collected by centrifugal separation of the autologous
      blood, and were stained with indocyanine green (ICG) dye. The ICG-stained
      leukocyte fluid was injected into an ear vein, and fundus images were obtained by
      infrared laser and a scanning laser ophthalmoscope. Experimental acute
      hypertension was induced by the intravenous drip injection of angiotensin II
      (AII). RESULTS: The fluorescent dots rapidly moved in choroidal arteries at a
      decreasing velocity, passed very slowly through choroidal capillaries and drained
      into choroidal veins. Under normal blood pressure, the mean leukocyte velocities
      in arteries, capillaries and veins were 8.63+/-1.68, 0.52+/-0.07, and 6.96+/-2.20
      mm/s, respectively. On the other hand, the respective mean velocities in acute
      hypertension induced by AII were 13.50+/-1.82, 0.81+/-0.09, and 10.54+/-3.91
      mm/s. Besides flow velocity, no change in leukocyte dynamics was observed.
      CONCLUSIONS: Under the condition of acute hypertension induced by AII, leukocytes
      moved faster in the total choroidal circulation (from arteries to veins) compared
      to their velocity under the condition of normal blood pressure. Blood velocities
      might increase in the total choroidal circulation at an early stage in acute
      hypertension induced by AII, resulting in increased choroidal blood flow. ILA
      makes it possible to evaluate the changes in choroidal circulation under various
      pathologic conditions.

PMID- 14636848
TI  - Disposable eyelid-warming device for the treatment of meibomian gland
      dysfunction.
AB  - PURPOSE: To assess the clinical efficacy of a newly developed disposable eyelid
      warming device (Eye Warmer) for the treatment of meibomian gland dysfunction
      (MGD). METHODS: The Eye Warmer was applied for 5 minutes to 44 eyes of 22
      patients who exhibited decreased tear break-up time (BUT) and dry-eye symptoms.
      Its efficacy was assessed on the basis of BUT and dry-eye symptoms in the short
      term study. In the therapeutic study, the Eye Warmer was applied to 34 eyes of 17
      MGD patients with decreased BUT and dry-eye symptoms for 5 minutes once a day for
      2 weeks. The 16 eyes of 8 patients served as untreated controls. We examined tear
      film lipid layer interference patterns, BUT, meibomian gland secretion, and dry
      eye symptoms in both groups before and after the treatment. RESULTS: BUT and dry
      eye symptoms significantly improved after the treatment in both the short-term
      and the therapeutic study (P<.01). The incidence of normal tear lipid layer in
      the treated group was significantly higher after treatment (28 eyes [82.4%]) than
      before (19 eyes [55.9%]) (P=.036). The incidence of meibomian gland obstruction
      was significantly decreased after treatment (14 eyes [41.2%]) compared to before
      treatment (26 eyes [76.5%]) (P=.006). CONCLUSIONS: Warming the eyelids with the
      Eye Warmer improved the stability and uniformity of the tear lipid layer in MGD
      patients by melting the meibomian gland lipid. Our study demonstrates the
      usefulness of the Eye Warmer for the treatment of MGD.

PMID- 14636849
TI  - Reversible Horner's syndrome and dysthyroid ocular myopathy associated with
      Hashimoto's disease.
AB  - BACKGROUND: Although it has been frequently stated that thyroid disease induces
      Horner's syndrome, there have been few reports describing the anatomical relation
      of goiter to the cervical preganglionic sympathetic nerve fibers in acquired
      Horner's syndrome, which is identified by the eye-drop test for adrenergic
      sensitivity. CASE: A 40-year-old woman with Hashimoto's disease presented with
      vertical diplopia, and blepharoptosis and miosis on the left side. OBSERVATIONS:
      Computed tomography scan showed hypertrophy of the right inferior rectus muscle,
      which resulted from a dysthyroid process, causing the limitation of upward
      movement of the right eye. The eye-drop test for adrenergic sensitivity revealed
      that only the left pupil dilated significantly after administration of 5%
      tyramine, and the Mueller's muscle on the left side did not respond. These
      results suggest that Horner's syndrome was due to a preganglionic sympathetic
      lesion. Magnetic resonance imaging (MRI) of the neck showed chronic inflammatory
      lesions in both lobes of the thyroid gland identified by a high-intensity signal.
      CONCLUSION: The reconstruction technique of MRI demonstrated that the swollen
      left lobe of the thyroid gland was compressing the pathway of the cervical
      preganglionic sympathetic nerve fibers.

PMID- 14636850
TI  - A case of Vogt-Koyanagi-Harada disease with good visual acuity in spite of
      subfoveal fold.
AB  - BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease patients with the complication of
      subretinal pigmented proliferative tissue tend to have a poor visual prognosis.
      CASE: We herein report a case of VKH with good visual acuity despite a prominent
      subretinal fold. OBSERVATIONS: A 24-year-old woman, who experienced several
      recurrent episodes of VKH disease, had bilateral serous retinal detachment with
      poor vision (RE 20/40 and LE 20/25). After the administration of high doses of
      systemic corticosteroids and D-mannitol, the subretinal fluid disappeared and the
      sensory retinas gradually became reattached. During the course of therapy,
      prominent pigmented subretinal strands were formed in both eyes. Optical
      coherence tomography disclosed that the strands existed at the retinal pigment
      epithelium level. Amazingly, we observed a change in the location of the fold in
      the posterior retina during the course of the disease. The patient finally showed
      the "sunset glow" fundi and a subretinal fold that was located almost directly
      beneath both fovea. Fortunately, this patient was able to recover and finally
      achieve a good visual acuity (RE 20/17 and LE 20/17). CONCLUSION: We reported a
      VKH disease patient with a good visual acuity despite a remarkable subfoveal
      fold, which changed its location during the course of the disease.

PMID- 14636851
TI  - Photodynamic therapy with delayed light application for the treatment of
      bilateral subfoveal choroidal neovascularization in age-related macular
      degeneration.
AB  - PURPOSE: To determine if photodynamic therapy (PDT) with delayed light
      application at 17 minutes after the start of infusion was effective in the second
      eyes of patients with bilateral subfoveal classic choroidal neovascularization
      (CNV) secondary to age-related macular degeneration (AMD). METHODS: The records
      of 20 patients with bilateral subfoveal classic CNV secondary to AMD who were
      treated with bilateral PDT in the same session were reviewed. Treatment for the
      second eye of patients was begun 120 seconds after termination of treatment for
      the first eye. This time interval was necessary for applying the contact lens and
      entering the new laser parameters, and it was kept constant in all cases. Best
      corrected visual acuity (BCVA), ophthalmologic examinations, fluorescein and
      indocyanine angiograms were used to evaluate the results of PDT. Follow-up time
      ranged from 6 to 12 months with a mean of 8.7 (+/-2.1) months. RESULTS: Mean (+/
      SD) treatment sessions were 1.7 (+/-0.6) in first eyes and 1.7 (+/-0.5) in second
      eyes. Among first eyes, BCVA improved in 7 of the 20 eyes (35%); stabilized in 7
      eyes (35%); and worsened in 6 eyes (30%). Among second eyes, BCVA improved in 5
      of the 20 eyes (25%); stabilized in 8 eyes (40%); and worsened in 7 eyes (35%).
      CONCLUSIONS: In most cases, bilateral PDT in the same session achieved cessation
      of fluorescein leakage from CNV without loss of vision or growth of CNV in the
      second eyes of patients with bilateral subfoveal classic CNV secondary to AMD.
      Further studies with a larger number of patients and longer follow-up are
      necessary to confirm whether bilateral PDT in the same session is beneficial for
      bilateral subfoveal classic CNV related to AMD.

PMID- 14636852
TI  - A case of uveal, palpebral, and orbital invasions in adult T-Cell leukemia.
AB  - BACKGROUND: Patients with adult T-cell leukemia (ATL) may have eyelid lymphoma,
      uveitis, or cytomegalovirus retinitis due to being immunocompromised. However,
      there have been few reports on the invasion of multiple ocular lesions. We
      treated 1 unusual ATL patient with uveitis in whom multiple ocular invasions were
      suspected. CASE: A woman in whom ATL was diagnosed 10 years previously complained
      of blurred vision and decreased visual acuity in the right eye. Anterior uveitis
      of the right eye was suspected. One week later the cells increased in the
      anterior chamber, and fibrin exudates and hyphema appeared. She was admitted to
      our hospital. OBSERVATIONS: The visual acuity was 0.04 in the right eye and
      finger-counting from 30 cm in the left. She was treated with systemic steroid
      therapy. Inflammation disappeared, but both eyelids became swollen and multiple
      ocular lesions appeared. She was given carcinostatic therapy once more and the
      mass lesions decreased. Mass lesions appeared in the iris and in the bulbar
      conjunctiva. Computed tomography and magnetic resonance imagining (MRI) showed
      that the mass lesions extended to the right orbit and both nasal cavities. MRI
      also demonstrated choroidal thickening in the left eye. CONCLUSION: This case
      documents that ATL cells may cause severe uveitis and invade multiple ocular
      tissues such as the iris, eyelid, choroids, and orbit.

PMID- 14636853
TI  - Ocular manifestations and prognosis of secondary glaucoma in patients with
      carotid-cavernous fistula.
AB  - PURPOSE: To study the frequency of ocular manifestations and the prognosis of
      secondary glaucoma in cases of carotid-cavernous fistula (CCF). METHODS: A
      retrospective multicenter study was conducted to investigate causes, types,
      ocular symptoms, complications, treatment, and prognosis in subjects with CCF.
      RESULTS: Among the 43 patients diagnosed with CCF between 1984 and 2000, a total
      of 13 patients (14 eyes) showed ocular manifestations. CCF was idiopathic in 13
      eyes of 12 subjects and resulted from head trauma in 1 eye of 1 subject. Among
      the ocular symptoms and complications, conjunctival hyperemia was most common,
      occurring at a rate of 92.9% of the eyes, followed by exophthalmos at 50%,
      retinal hemorrhaging at 50%, retinal venous dilation at 42.9%, vascular bruits at
      28.6%, injection of Schlemm's canal at 21.4%, and external ophthalmoplegia at
      21.4%. Elevated intraocular pressure (IOP) occurred at a rate of 64.3%, with
      maximum IOP ranging from 22-55 mm Hg. At the time of the final observation, IOP
      control was favorable in 6 of the 9 eyes showing elevated IOP; 5 of these 9 eyes
      showed a closed CCF, but none required antiglaucoma treatment, with the exception
      of 1 eye for which trabeculectomy was performed. IOP control was unfavorable in
      the remaining 3 eyes, and in 1 of these eyes CCF was not closed. CONCLUSIONS:
      Secondary glaucoma is a frequently observed ocular manifestation of CCF, and
      closure of the fistula is the primary condition required for favorable IOP
      control.

PMID- 14636854
TI  - Evaluation of staphylococcal enterotoxin-specific IgE antibody in tears in
      allergic keratoconjunctival disorders.
AB  - PURPOSE: To investigate the presence of staphylococcal enterotoxin A (SEA) and B
      (SEB)-specific IgE antibodies in tears from patients with allergic conjunctival
      disorders. METHODS: The study included 8 eyes of 4 patients with perennial
      allergic conjunctivitis (PAC), 14 eyes of 7 patients with vernal
      keratoconjunctivitis (VKC), 12 eyes of 6 patients with atopic
      keratoconjunctivitis (AKC), and 10 eyes of 10 healthy volunteers as controls.
      Tears were sampled by the method of the Schirmer test I. Sampled tears were
      eluted and SEA- and SEB-specific IgE antibodies were analyzed by the AlaSTAT
      IMMULIZE method. RESULTS: SEA-specific IgE antibodies in tears were positive in 9
      of 14 eyes in VKC patients and in 1 of 12 eyes in AKC patients. SEB-specific IgE
      antibodies in tears were positive in 7 of 14 eyes in VKC patients and in 2 of 12
      eyes in AKC patients. Values for antibodies were higher in patients with severe
      clinical findings. However, all the cases in the normal control and the PAC
      groups were negative for both antibodies. CONCLUSION: Our data strongly suggested
      that staphylococcal enterotoxin may cause type I allergy, and may be an
      exacerbating factor for vernal keratoconjunctivitis and atopic
      keratoconjunctivitis.

PMID- 14636855
TI  - Coloration of fundus lesions in bilateral diffuse uveal melanocytic
      proliferation.
AB  - PURPOSE: To report differences in the coloration of fundus lesions between Asian
      and Caucasian patients with bilateral diffuse uveal melanocytic proliferation
      (BDUMP). CASES: This syndrome was detected in 2 Japanese patients, 69 and 73
      years old, with lung cancer who visited our department complaining of visual
      disturbances. The coloration of the fundus lesions was investigated in these 2
      patients. RESULTS: The fundus lesions in the first patient appeared gray or
      grayish-brown in color at the first visit. Six months later, the fundus appeared
      as a mixture of white to dark-brown lesions. The fundus in the second patient
      exhibited a mixture of white, gray, and dark-brown lesions from the first visit.
      CONCLUSIONS: The fundus lesions in these BDUMP patients appeared gray or grayish
      brown in color at the early stage of the disease, probably because of the
      abundance of melanin pigments in the uveal melanocytes. At the advanced stage,
      the fundus exhibited a mixture of dark-brown lesions due to melanin deposits and
      white, depigmented lesions caused by atrophy and/or necrosis of the melanocytes.

PMID- 14636856
TI  - A novel combination treatment of chlorhexidine gluconate, natamycin (pimaricin)
      and debridement for a Acanthamoeba keratitis.

PMID- 14636857
TI  - Bullous keratopathy after argon laser iridotomy presumably associated with
      latanoprost.

PMID- 14636858
TI  - Pulsatile ocular blood flow is unaffected in type 2 diabetes mellitus.

PMID- 14636871
TI  - Significance of elevated cobalamin (vitamin B12) levels in blood.
AB  - Elevated levels of serum cobalamin may be a sign of a serious, even life
      threatening, disease. Hematologic disorders like chronic myelogeneous leukemia,
      promyelocytic leukemia, polycythemia vera and also the hypereosinophilic syndrome
      can result in elevated levels of cobalamin. Not surprisingly, a rise of the
      cobalamin concentration in serum is one of the diagnostic criteria for the latter
      two diseases. The increase in circulating cobalamin levels is predominantly
      caused by enhanced production of haptocorrin. Several liver diseases like acute
      hepatitis, cirrhosis, hepatocellular carcinoma and metastatic liver disease can
      also be accompanied by an increase in circulating cobalamin. This phenomenon is
      predominantly caused by cobalamin release during hepatic cytolysis and/or
      decreased cobalamin clearance by the affected liver. Altogether it can be
      concluded that an observed elevation of cobalamin in blood merits the a full
      diagnostic work up to assess the presence of disease.

PMID- 14636872
TI  - Evaluation of an algorithm for calculation of serum "bioavailable" testosterone
      (BAT).
AB  - OBJECTIVES: To evaluate a recently published algorithm for calculation of serum
      "Bioavailable" Testosterone (BAT) using serum Total Testosterone (TT), Sex
      Steroid Binding Globulin (SSBG) [also commonly known as Sex Hormone Binding
      Globulin (SHBG)] and albumin concentrations as parameters, in comparison with a
      locally available "salting-out" BAT method. If satisfactory, this calculation
      could serve as a substitute for the BAT assay, which would amount to a major cost
      saving and faster turnaround time. DESIGN AND METHODS: During a 6-month period,
      426 serum samples referred for BAT analysis to the Hospitals In-Common Laboratory
      of Toronto were also analyzed in-house for TT, SSBG and albumin for computation
      of comparison calculated BAT results. RESULTS: A good statistical correlation was
      obtained, but only after unexpectedly drastic empirical modification of the
      association constant values: r=0.95, Calculated %BAT=0.971 x Measured %BAT +
      0.008. The endocrinologist/andrologist of our team (JB), who was the responsible
      physician for all patients included in this study, reviewed the tabulated and
      charted calculated BAT results and verified that they were clinically equivalent.
      CONCLUSIONS: Although it is feasible to calculate BAT, the algorithm is not
      directly portable. Before adopting such a calculation each laboratory should
      compare it with the locally available BAT method and consider adjusting the
      calculation to optimize the correlation. Future reassessment may be necessary
      whenever the SSBG, TT or BAT assay is changed.

PMID- 14636873
TI  - Structural analysis, fatty acid and thyroxine binding properties of Vancouver and
      Naskapi variants of human serum albumin.
AB  - OBJECTIVES: To purify and structurally identify two albumin variants found in the
      Canadian population of native Amerindian origin. To assess the ability of variant
      albumins to bind lauric acid and L-thyroxine. METHODS: The structural
      characterization of the alloalbumins was performed by conventional protein
      chemistry methods and by mass spectrometric analysis. Lauric acid and L-thyroxine
      affinities to variant albumins were assessed by kinetic dialysis and equilibrium
      dialysis techniques, respectively. RESULTS: The sequence investigations proved
      the two variants to be albumin Naskapi [372Lys --> Glu] and albumin Vancouver
      [501Glu --> Lys], respectively. Among the carriers of albumin Naskapi, we found a
      rare case of homozygosity. Furthermore, this is the first reported case of the
      501Glu-->Lys mutation in the native North American population. Scatchard plot
      analysis revealed that the association constants for lauric acid and L-thyroxine
      to the two variants were indistinguishable from the endogenous form of albumin.
      CONCLUSION: We show that albumin variants Vancouver and Naskapi have normal fatty
      acid and L-thyroxine binding capabilities. These findings support the assumption
      that bisalbuminemias associated with these albumin variants are benign
      conditions.

PMID- 14636874
TI  - Evaluation of the analytic performances of the new HPLC system HLC-723 G7 for the
      measurement of hemoglobin A1c.
AB  - OBJECTIVES: The analytical performance of a new automated HPLC system, for the
      determination of HbA1C in blood (Tosoh HLC-723 G7), was studied. DESIGN AND
      METHODS: The study design included the evaluation of imprecision, linearity,
      interference and carryover. Comparison study was performed by comparing HbA1C
      results with those obtained from an established method (Bio-Rad Variant II).
      RESULTS: Total imprecision was less than 1.34% and the results were linear up to
      17.2% HbA1C. The method showed a wide analytical range, and no carryover between
      specimens. Comparison study yielded, r=0.989, Sy.x=0.255, regression equation
      (y=0.9895x-0.35); Bland-Altman plot showed a mean bias=- 0.43% HbA1C with
      confidence limits ranging from -0.48% to -0.38% HbA1C. The presence of abnormal
      hemoglobin was clearly revealed, and no interference from labile HbA1C was
      apparent. CONCLUSION: The HLC-723 G7 instrument seems to be a reliable system for
      routine assay of HbA1C.

PMID- 14636876
TI  - An improved assay for plasma methylmalonic acid using chemical ionization gas
      chromatography mass spectrometry.
AB  - OBJECTIVES: To develop a precise and sensitive assay for methylmalonic acid (MMA)
      using positive chemical ionization gas chromatography mass spectrometry (CI GC
      MS), and to illustrate its clinical utility. METHODS: Using the developed assay,
      reference intervals were determined with 108 ambulatory individuals, and
      potential clinical utility examined in 178 consecutive patients with possible
      cobalamin deficiency (serum B12<200 nmol/L). RESULTS AND CONCLUSIONS:
      Methylmalonic acid measured by CI GC-MS was precise (CV: 4-5%), and sensitive
      (limit of quantitation: 37 nmol/L). In a clinical reference set, 37% of
      individuals with serum B12 less than 200 pmol/L had plasma MMA concentrations
      within the reference interval (75-378 nmol/L), rendering cobalamin deficiency
      unlikely. The observation illustrates that MMA assay may be a useful adjunct test
      in assessing patients with low serum B12.

PMID- 14636875
TI  - Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in
      patients with autoimmune thyroid disease.
AB  - OBJECTIVES: To verify the cut-off values and to determine the clinical
      sensitivity of antithyroglobulin (TgAb) determinations using our routine RIA and
      the new electrochemiluminescent Elecsys assay. DESIGN AND METHODS: We used the
      DYNOtest anti-Tgn manual RIA from BRAHMS and the new automated Elecsys
      electrochemiluminescent immunoassay from Roche Diagnostics. We analyzed 452 sera
      from the following subjects: 193 euthyroid controls, 163 with treated and
      untreated autoimmune thyroid diseases (AITD) (108 Graves' disease and 55
      thyroiditis), 50 with differentiated thyroid carcinoma, 13 with nonautoimmune
      thyroid disease and 33 with type 1 diabetes mellitus. RESULTS: As expected, using
      the proposed thresholds (BRAHMS 60 kIU/L, Elecsys 115 kIU/L) approximately 6% of
      the control subjects were positive for TgAb with both methods. In AITD patients,
      the sensitivity of TgAb determination was significantly higher with the Elecsys
      assay (51.5%) than with the BRAHMS assay (39.3%). This difference was not
      observed in the other patient groups. CONCLUSION: The Elecsys assay can be
      preferred not only because it is automated and rapid, but also because of its
      better clinical performance in AITD patients.

PMID- 14636877
TI  - Improved TRAP-silver staining versus conventional radioactive TRAP assays:
      quantification of telomerase activity during immortalization and in pathological
      human endometrium.
AB  - OBJECTIVES: To develop a sensitive telomeric repeat amplification protocol (TRAP)
      silver staining assay for telomerase activity quantification. DESIGN AND METHODS:
      TRAP assays were performed by using a TRAPeze telomerase kit with or without
      [alpha-32P]-dCTP. Amplification products were electrophoresed in polyacrylamide
      gels and detected by autoradiography or a modified silver staining protocol.
      Telomerase activity was quantified from radioactive counts or optical density of
      telomerase products from test extracts and controls. RESULTS: TRAP-silver
      staining assay was at least as sensitive as radioactive TRAP assay and quantified
      telomerase activity within linearity from 10 to 3,000 cell equivalents. Both
      methods quantified a weak telomerase activity in normal endometrial glandular
      epithelial cells (GEC) and a strong increase in immortalized GEC. In human
      pathologic endometria (n=24), telomerase activity was correlated with lesion
      seriousness and distinguished simple hyperplasias from nonhyperplasic or
      cancerous lesions. CONCLUSIONS: TRAP-silver staining assay is suitable for cell
      and tissue telomerase activity routine quantification.

PMID- 14636878
TI  - Influence of anticoagulants on the measurement of S100B protein in blood.
AB  - OBJECTIVE: Evaluate anticoagulants influence on blood S100B levels. DESIGN AND
      METHODS: Blood from 18 healthy adult subjects were collected using: no
      anticoagulants; EDTA; heparin; and citrate. S100B levels were determined using
      LIA-mat assay. RESULTS: Heparin and citrate increased S100B levels (p<0.001),
      whereas EDTA had no effect (p=0.24). Heparin samples were highly (r2=0.97,
      p<0.001), citrate samples were moderately (r2=0.49, p<0.001), and EDTA samples
      were not (r2=0.22, p=0.059) correlated with serum samples. CONCLUSION: When
      anticoagulant is required, heparin should be the primary choice.

PMID- 14636879
TI  - A homogeneous high-throughput genotyping method based on competitive
      hybridization.
AB  - OBJECTIVES: A reliable high-throughput assay system is necessary for the analysis
      of the ever-increasing numbers of single-nucleotide polymorphisms (SNP) relevant
      to genetic screening studies. We describe an assay suitable also for large-scale
      screening programs. DESIGN AND METHODS: The one-step assay is based on asymmetric
      PCR amplification of the target sequence and subsequent time-resolved
      fluorescence measurement. Asymmetric amplification results in a single-stranded
      PCR product that is detected in the amplification vessel with a highly sensitive,
      homogeneous hybridization method. RESULTS: A dual label, homogeneous high
      throughput platform for nucleic acid sequence analysis was developed and
      validated using a C/T single-nucleotide polymorphism in the insulin gene as a
      model analyte and applied also to two other SNP-assays (poliovirus receptor A/G
      polymorphism and CD86-gene exon 2 A/G-polymorphism). CONCLUSIONS: The described
      high-throughput genotyping technology is very competitive in price, simple in
      design and easily applied to any analyte sequence.

PMID- 14636880
TI  - APOA1 related amyloidosis: a case report and literature review.
AB  - OBJECTIVES: Amyloidosis results from local or systemic extracellular deposition
      of insoluble protein fibrils and is associated with certain rare mutations in
      APOA1 encoding apolipoprotein (apo) A-I. DESIGN AND METHODS: In a patient with
      renal-predominant amyloidosis with neuropathy, we found the APOA1 G26R mutation.
      CONCLUSIONS: While the spectrum of APOA1 mutations provides no particular
      mechanistic insights, molecular diagnosis may still be important due to clinical
      differences between amyloidosis resulting from mutation in APOA1 vs. other genes.

PMID- 14636881
TI  - Hyperglycosylated hCG (invasive trophoblast antigen, ITA) a key antigen for early
      pregnancy detection.
AB  - OBJECTIVES: Hyperglycosylated human chorionic gonadotrophin (hCG) is an hCG
      variant with extra-large O-linked oligosaccharides, produced by phenotypically
      invasive cytotrophoblast cells in choriocarcinoma and pregnancy. It is the
      principal form of hCG produced in the first weeks of gestation. We investigated
      the importance of hyperglycosylated hCG in pregnancy testing and its detection by
      current hCG tests. DESIGN AND METHODS: We measured the concentration of
      hyperglycosylated hCG and total hCG in 512 pregnancies throughout gestation. We
      assessed and compared the abilities of 14 commonly used commercial laboratory hCG
      tests and 18 home pregnancy tests to detect regular and hyperglycosylated hCG.
      RESULTS: Hyperglycosylated hCG is the principal source of hCG-related
      immunoreactivity in early pregnancy. In the week following missing menses,
      hyperglycosylated hCG measurements may be more sensitive than regular hCG
      measurements in detecting pregnancy. Of 14 commercial laboratory hCG tests, 3
      appropriately detected hyperglycosylated hCG standard. Of 18 different home
      pregnancy products 11 poorly or very poorly detected this key antigen.
      CONCLUSIONS: Hyperglycosylated hCG may be the key molecule in the detection of
      early pregnancy. However, the majority of tests poorly detected or failed to
      detect this key antigen. New pregnancy tests are needed that either solely detect
      hyperglycosylated hCG or equally detect regular hCG and hyperglycosylated hCG.

PMID- 14636882
TI  - Low-density lipoprotein subclass and its correlating factors in diabetics.
AB  - OBJECTIVES: Small dense LDL, low density lipoprotein (LDL) particles with small
      size and high density, is regarded as a significant risk factor for
      cardiovascular diseases. Diabetes mellitus is one of the conditions accompanied
      by increased small dense LDL. We analyzed LDL subclass in type 2 diabetics and
      normal controls with LipoPrint LDL System to investigate the LDL heterogeneity in
      diabetics and factors affecting it. DESIGN AND METHODS: We selected 40 normal
      controls and 40 type 2 diabetics with fasting blood glucose level over 7.0 mmol/L
      and HbA1c level over 7%. LDL subclass was determined with LipoPrint LDL System.
      LipoPrint LDL System fractionates LDL into seven parts (LDL1-7) by size and LDL3
      to LDL7 are defined as small-sized LDL. In addition we estimated 'the percent of
      small-sized LDL over whole LDL' and defined it as 'small-sized LDL proportion'.
      RESULTS: Mean small-sized LDL proportion was significantly higher in diabetics
      (23.4%) than in controls (11.8%) (p<0.001) and small-sized LDL proportion showed
      positive correlation with blood levels of glucose, HbA1c, total cholesterol,
      triglyceride, and oxidized LDL and negative correlation with HDL cholesterol
      level in univariate analysis (p<0.001). Of these parameters, triglyceride, HbA1c,
      oxidized LDL were statistically significant variables contributing to the small
      sized LDL proportion in stepwise multiple regression analysis. CONCLUSIONS: We
      analyzed small-sized LDL proportion in type 2 diabetics and found that it was
      significantly increased in diabetics than control subjects and it was
      independently correlated with triglyceride, HbA1c, oxidized LDL in descending
      order, which are reflecting lipid metabolism, glycation, and oxidative stress,
      respectively.

PMID- 14636883
TI  - Do glycoprotein IIb/IIIa inhibitors interact with assays for myocardial necrosis?
AB  - OBJECTIVES: To determine whether glycoprotein (GP) IIB/IIIA inhibitors interact
      with cardiac marker assays: total creatine kinase (CK), CK-MB, and troponin-I
      (TnI). DESIGN AND METHODS: Two blood samples were collected during coronary
      angiography or angioplasty and analyzed for cardiac markers: one after arterial
      sheath insertion and the second 10 mins later. In the first phase (n=101),
      heparin and GP IIb/IIIa inhibitors were given between samples, in the second
      phase (n=45) only heparin was given, and in the third phase (n=54) neither drug
      was given. RESULTS: In each phase, there was a significant decline in total CK
      over the 10 min period. There were no consistent significant changes in CK-MB or
      TnI. CONCLUSIONS: Neither GP IIb/IIIa inhibitors nor i.v. heparin interact with
      cardiac marker assays. There is a small but significant decline in total CK
      levels within 10 mins of arterial puncture that is unrelated to administration of
      these drugs.

PMID- 14636884
TI  - Death receptor-induced cell killing.
AB  - Apoptosis pathways activated by death receptors of the tumour necrosis factor
      (TNF) family such as Fas, TNFR1, or the TRAIL receptors DR4 and DR5 are
      implicated in diverse diseases. These are also the best-understood apoptosis
      pathways and many of our ideas about apoptosis regulation come from studying
      these pathways. Cell killing from such receptors occurs because of recruitment to
      the receptor of the adaptor protein FADD, which in turn recruits the pro form of
      caspase-8. Aggregation of pro-caspase-8 leads to its auto-activation and
      subsequent activation of effector caspases such as caspase-3. The apoptotic
      signal can be amplified through the mitochondria and inhibited through the action
      of competing molecules such as the inhibitor c-FLIP, which binds to the receptor
      complex in place of caspase-8. This simple mechanism explains much of the cell
      death that is induced by death receptors. However, recent studies indicate that
      we must incorporate new information into this model. Some examples that add new
      layers of complexity will be discussed in this review.

PMID- 14636885
TI  - Bcr-Abl-mediated molecular mechanism for apoptotic suppression in multipotent
      haemopoietic cells: a role for PKCbetaII.
AB  - Bcr-Abl protein tyrosine kinase (PTK) activity is a feature of chronic myeloid
      leukaemia and confers a survival advantage on haemopoietic progenitor cells. We
      have expressed conditional mutant of the Bcr-Abl PTK in the FDCP-Mix A4
      multipotent haematopoietic cell line in order to examine the molecular mechanisms
      whereby Bcr-Abl PTK leads to enhanced cell survival under conditions in which
      normal cells die. Activation of Bcr-Abl PTK does not phosphorylate or activate
      either ERK-1/2 or JAK-2/STAT-5b, suggesting that these signal transduction
      pathways are not involved in Abl PTK-mediated suppression of apoptosis in FDCP
      Mix cells. However, protein kinase C (PKC) does have a role to play. Inhibition
      of PKC results in a reversal of Bcr-Abl PTK-mediated survival in the absence of
      growth factor and Bcr-Abl stimulates translocation of the PKCbetaII isoform to
      the nucleus. Furthermore, expression of a constitutively activated PKCbetaII in
      haemopoietic progenitor FDCP-Mix cells stimulates enhanced cell survival when IL
      3 is withdrawn. However, expression of this constitutively activated PKC isoform
      does not suppress cytotoxic drug-induced apoptosis. Thus Bcr-Abl PTK has
      pleiotropic effects which can suppress cell death induced by a number of stimuli.

PMID- 14636886
TI  - Arachidonic acid regulates two Ca2+ entry pathways via nitric oxide.
AB  - Several regulated Ca2+ entry pathways have been identified, with capacitative
      Ca2+ entry (CCE) being the most characterized. In the present study, we examined
      Ca2+ entry pathways regulated by arachidonic acid (AA) in mouse parotid acini. AA
      induced Ca2+ release from intracellular stores, and increased Ca2+ entry. AA
      inhibited thapsigargin (Tg)-induced CCE, whereas AA activated Ca2+ entry when CCE
      was blocked by gadolinium (Gd3+). AA-induced Ca2+ entry was associated with
      depletion of calcium from ryanodine-sensitive stores; both AA-induced Ca2+
      release and Ca2+ entry were inhibited by tetracaine and the nitric oxide synthase
      (NOS) inhibitor, 7-nitroindazole (7-NI). The nitric oxide (NO) donor, 1,2,3,4-ox
      triazolium,5-amino-3-(3,4-dichlorophenyl)-chloride (GEA 3162), but not 8-bromo
      cGMP, mimicked the effects of AA in inhibiting CCE. Results suggest that AA acts
      via nitric acid to inhibit the CCE pathway that is selective for Ca2+, and to
      activate a second Ca2+ entry pathway that is dependent on depletion of Ca2+ from
      ryanodine-sensitive stores.

PMID- 14636887
TI  - Interferon-alpha inhibits interleukin-3-induced proliferation of Ba/F3 cells in a
      protein kinase R-dependent manner.
AB  - We have previously shown that interferon-alpha (IFN-alpha) inhibits proliferation
      of Ba/F3 cells by interfering with the action of the mitogen interleukin-3 (IL-3)
      [Cell Signal 11 (1999) 769]. Here, we have characterised the role of protein
      kinase R (PKR), an IFN-alpha-inducible enzyme, in the mediation of IL-3
      antagonistic IFN-alpha effects. Downregulation of PKR expression by antisense
      oligonucleotide treatment blocked IFN-alpha-induced growth inhibition. Reduction
      of PKR levels and overexpression of a dominant-negative PKR mutant correlated
      with diminished inhibitory IFN-alpha effects on the IL-3-dependent expression of
      a luciferase reporter construct, GAS-luc. Furthermore, increased nuclear levels
      of STAT1 (bound in ISGF3 complexes) were observed in PKR-depleted cells cultured
      with or without IFN-alpha. Together, our data indicate an essential role of PKR
      in the mediation of IL-3-antagonistic IFN-alpha effects on Ba/F3 cells. They also
      suggests that activation of STAT1, an essential mediator of IFN effects, is
      insufficient for growth inhibition if PKR is not expressed.

PMID- 14636888
TI  - Dimerization of G-protein-coupled receptors: roles in signal transduction.
AB  - Recently, many G-protein-coupled receptors (GPCRs) have been demonstrated to form
      constitutive dimers consisting of identical or distinct monomeric subunits. The
      discovery of GPCR dimerization has revealed a new level of molecular cross-talk
      between signalling molecules and may define a general mechanism that modulates
      the function of GPCRs under both physiological and pathological conditions. The
      heterodimerization between distinct GPCRs could be responsible for the generation
      of pharmacologically defined receptors for which no gene has been identified so
      far. Elucidating the role of dimerization in the activation processes of GPCRs
      will lead us to develop novel pharmaceutical agents that allosterically promote
      activation or inhibition of GPCR signalling.

PMID- 14636889
TI  - Akt/GSK3beta serine/threonine kinases: evidence for a signalling pathway mediated
      by familial Alzheimer's disease mutations.
AB  - Although Alzheimer's disease pathologically affects the brain, familial
      Alzheimer's disease associated mutations of beta-amyloid precursor protein and
      presenilin are ubiquitously expressed and therefore aberrant intracellular
      signals, separate from but similar to, the brain may be expected. Here, we report
      selective down regulation of the serine/threonine kinase, Akt/PKB, concurrent
      with elevated endogenous GSK3beta kinase activity in familial Alzheimer's disease
      beta-amyloid precursor protein expressing human embryonic kidney (HEK) and
      familial Alzheimer's disease presenilin lymphoblast cells. Further, familial
      Alzheimer's disease presenilin in the human lymphoblast was associated with beta
      catenin destabilization. Moreover, limited immunohistochemistry analysis reveals
      Akt/PKB in a subset of neurofibrillary tangles where GSK3beta and tau have been
      reported to co-localize, suggesting a possible Akt/GSK3beta and tau interaction
      in vivo. Our data suggest that familial Alzheimer's disease mutants of beta
      amyloid precursor protein and presenilin signal, at least in part, through the
      Akt/GSKbeta pathway and that Akt/GSK3beta-mediated signalling may contribute to
      the underlying Alzheimer's disease pathogenesis induced by familial Alzheimer's
      disease mutants.

PMID- 14636890
TI  - Role of Lbc RhoGEF in Galpha12/13-induced signals to Rho GTPase.
AB  - Heterotrimeric Galpha12/13 signals induce cellular responses such as serum
      response element (SRE)-mediated gene transcription via Rho GTPase. Guanine
      nucleotide exchange factors (GEFs) are strong candidates for linking Galpha
      signals to Rho. For example, p115 RhoGEF transduces Galpha13 signals to Rho and
      inhibits Galpha12/13 signals via the RhoGEF LH domain which links to Galpha
      subunits. Here, we have evaluated the signaling capacity of Lbc RhoGEF in the
      context of Galpha12/13 signals. In vitro GEF assays indicate that baculoviral
      expressed proto-Lbc has minimal exchange activity, implying that a stimulus is
      required for Lbc activity in vivo. Expression of a catalytically inactive proto
      Lbc mutant in HEK293T cells attenuates Galpha12- and thrombin-induced activation
      of an SRE transcriptional reporter, and the levels of inhibition observed is
      similar to that obtained with an analogous p115 RhoGEF mutant. proto-Lbc mutant
      expression also led to decreased levels of Galpha12-induced RhoA activation in
      vivo. Complex formation between Galpha12 and Lbc forms was detected. Analysis of
      the Lbc peptide sequence reveals a previously undetected region which may link to
      Galpha subunit signals. These findings support a role for Lbc in Galpha12-induced
      signaling pathways to Rho.

PMID- 14636891
TI  - Calcium pyrophosphate dihydrate crystal associated induction of neutrophil
      activation and repression of TNF-alpha-induced apoptosis is mediated by the p38
      MAP kinase.
AB  - The role of p38 mitogen-activated protein (MAP) kinase in the activation of human
      neutrophils and repression of TNF-alpha-induced apoptosis in response to plasma
      opsonized crystals of calcium pyrophosphate dihydrate (CPPD) was investigated. We
      monitored the endogenous phosphotransferase activity of p38 kinase in neutrophils
      stimulated with CPPD crystals (25 mg/ml) alone or in the presence of TNF-alpha
      (10 ng/ml), and with TNF-alpha alone. CPPD crystals induced a 2-fold activation
      of p38 kinase activity over the basal activity that was observed in untreated
      neutrophils. Furthermore, CPPD crystals repressed the TNF-alpha associated 6-fold
      induction of p38 kinase phosphotransferase activity to levels associated with
      CPPD crystal incubation alone in a PD98059 (20 ng/ml) and Wortmannin (100 nM)
      sensitive manner. Inhibition of CPPD crystal-induced activation of the neutrophil
      inflammatory response as measured by chemiluminescence, superoxide anion
      generation and degranulation as determined by myeloperoxidase and lysozyme
      release was observed in the presence of the specific p38 MAP kinase inhibitor
      SB203580 (5 microM). CPPD crystal associated repression of TNF-alpha-induced
      activation of neutrophil apoptosis as determined by DNA fragmentation correlated
      with the CPPD crystal mediated inhibition of p38 kinase activity, probably
      through crystal inhibition of caspase 3. Together, our results indicate that the
      CPPD crystal associated inflammatory response is regulated through the activation
      of p38 kinase to sub-apoptotic levels, and that the repression of the TNF-alpha
      induced apoptosis program in neutrophils is mediated via the repression of
      caspase 3 mediated apoptosis-associated p38 kinase activity.

PMID- 14636892
TI  - Opposite effects of inhibitors of mitogen-activated protein kinase pathways on
      the egr-1 and beta-globin expression in erythropoietin-responsive murine
      erythroleukemia cells.
AB  - The effect of erythropoietin (Epo) on the expression of mitogen-activated protein
      kinase (MAPK) target genes egr-1 and c-fos was investigated in Epo-responsive
      murine erythroblastic cell line ELM-I-1. Epo induced a transient rise in egr-1
      mRNA without a similar effect on c-fos expression. The induction of egr-1
      correlated with a rapid ERK1/2 phosphorylation and was prevented with MEK1/2
      inhibitors PD 98059 and UO126. The p38 inhibitor SB 203580 enhanced ERK1/2
      phosphorylation and egr-1 mRNA levels. Longer incubations of ELM-I-1 cells with
      Epo revealed a second later phase of increase in egr-1 expression which was also
      prevented by MEK1/2 inhibitors, whereas SB 203580 had a stimulatory effect. In
      contrast, the beta-globin mRNA production was enhanced in the presence of PD
      98059 and UO126 and reduced by SB 203580. The results suggest a regulatory role
      of egr-1 expression in Epo signal transduction and provide pharmacological
      evidence for the negative modulation of differentiation-specific gene expression
      by the ERK1/2 pathway in murine erythroleukemia cells.

PMID- 14636893
TI  - Dephosphorylation of cofilin is regulated through Ras and requires the combined
      activities of the Ras-effectors MEK and PI3K.
AB  - Remodeling of the actin cytoskeleton is crucial for a multitude of cellular
      functions including cell movement, intracellular transport as well as signal
      transduction and gene expression processes. Cofilin has been identified as a key
      mediator of actin reorganization. Its activity is regulated via reversible
      phosphorylation of ser-3. In a variety of cell types stimulation through
      particular surface receptors fastly induces the dephosphorylation/activation of
      cofilin. Yet, the signal transduction cascades linking receptor stimulation with
      cofilin activation have not been identified so far. Here we show that the GTPase
      Ras acts as a central regulator of the cofilin dephosphorylation pathway. Thus,
      stimulation of Ras through platelet-derived growth factor (PDGF) or transient
      expression of activated Ras-proteins induces the dephosphorylation of cofilin.
      Importantly, the cooperation of two Ras-initiated signaling pathways is required
      to induce cofilin dephosphorylation: a Ras-Raf-MAPkinase/Erk-kinase (MEK)- and a
      Ras-phosphatidylinositol-3-kinase (PI3K)-effector cascade.

PMID- 14636894
TI  - A possible role for p190RhoGAP in PKCepsilon-induced morphological effects.
AB  - We have previously shown that protein kinase C (PKC) epsilon induces neurite
      outgrowth via its regulatory domain. This is accompanied by PKC-induced stress
      fibre loss. Here, we show that the regulatory domain (RD) of PKCepsilon induces
      processes also in NIH-3T3 fibroblasts, similar to what has been observed with
      p190RhoGAP. This study also shows that p190RhoGAP induces neurite outgrowth in SK
      N-BE(2) neuroblastoma cells. We therefore investigated whether p190RhoGAP may be
      downstream of PKCepsilon. We could detect a co-localization of p190RhoGAP and
      PKCepsilon at membrane ruffles and an increased association between the proteins
      in fibroblasts treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). The
      association is also seen in neuroblastoma cells, and nerve growth factor (NGF)
      treatment of SH-SYSY/TrkA cells decreases the interaction. However, overexpressed
      PKCepsilon did not coprecipitate overexpressed p190RhoGAP in CHO cells,
      indicating that the proteins do not interact directly. This raises the
      possibility that p190RhoGAP is involved in mediating the morphological effects of
      PKCepsilon.

PMID- 14636895
TI  - Protein kinase G II-mediated proliferative effects in human cultured prostatic
      stromal cells.
AB  - This study investigates the effect of protein kinase G (PKG) activation upon
      proliferation of human cultured prostatic stromal cells. The PKG II activator (8
      pCPT-cGMP; IC50 of 113+/-42 nM) and the phosphodiesterase inhibitor, zaprinast
      (up to 50 microM), but not the PKG I isoform activators (APT-cGMP and PET-cGMP),
      reduced foetal calf serum-stimulated proliferation. The effect of 8-pCPT-cGMP (30
      microM) was blocked by Rp-8-Br-cGMPS (5 microM) and Rp-8-pCPT-cGMP (5 microM),
      but not Rp-cAMPS (5 microM). 8-pCPT-cGMP (30 microM) and zaprinast (50 microM),
      but not PET-cGMP (30 microM), caused a significant increase in atypical nuclei
      and an increase in annexin-V staining. These data indicate that activation of PKG
      II induces apoptosis of human cultured prostatic stromal cells.

PMID- 14636896
TI  - Cytosolic p21Waf1/Cip1 increases cell cycle transit in vascular smooth muscle
      cells.
AB  - The intracellular localization of signaling proteins is critical in directing
      their interactions with both upstream and downstream signaling cascade
      components. While initially described as a cyclin kinase inhibitor, p21Waf1/Cip1
      has since been shown to have bimodal effects on cell cycle progression and cell
      proliferation, and evidence is emerging that intracellular localization of this
      protein plays a role in directing its signaling properties by dictating its
      interactions with downstream molecules. Since we have previously demonstrated a
      pro-apoptotic and cell cycle inhibitory effect of p21 attenuation after
      transfection of antisense p21 oligodeoxynucleotides (ODN) in several cell lines,
      we asked whether cytosolic p21 mediates a positive effect on vascular smooth
      muscle (VSM) cell cycle transit. We now show that transfection of a nuclear
      localization signal deficient (DeltaNLS) p21 construct into VSM cells results in
      increased cytosolic levels of p21 and causes increased cell cycle transit as
      measured by [3H]thymidine incorporation. Thus, at least in VSM cells, cytosolic
      localization of p21 is a means by which this signaling protein transmits pro
      mitogenic signals to the proteins responsible for G1/S transition. Furthermore,
      compartmentalization of p21 may help explain the biphasic nature of p21 in a
      variety of cell types and may lead to therapeutic advances directed at modulating
      pathologic cell growth in vascular diseases and cancer.

PMID- 14636898
TI  - IL-7 induces tyrosine phosphorylation of clathrin heavy chain.
AB  - IL-7 induction of protein tyrosine phosphorylation was examined in an IL-7
      dependent thymocyte cell line, D1, which was generated from a p53-/- mouse. Anti
      phosphotyrosine antibody was used both to immunoprecipitate and Western blot, and
      showed that IL-7 induced tyrosine phosphorylation of a protein with a molecular
      weight of approximately 200 kDa. The P200 band was purified by reversed-phase
      high-performance liquid chromatography. Amino acid sequencing by mass
      spectrometry revealed three peptides identical to rat clathrin heavy chain (CHC)
      1 (192 kDa), and this was confirmed by blotting with an anti-clathrin antibody.
      Stimulation of normal pro-T cells by IL-7 showed an increased tyrosine
      phosphorylation of clathrin heavy chain. Tyrosine phosphorylation of clathrin
      heavy chain was strongly induced by IL-7 and to a lesser extent by IL-4, while no
      effect could be observed with the cytokines IL-2, IL-9 and IL-15, whose receptors
      share the gammac chain. Phosphorylation of clathrin heavy chain was found to be
      sensitive to Jak3 inhibitors but not to Src inhibitors. Clathrin is involved in
      internalization of many receptors, and its phosphorylation by IL-7 stimulation
      may affect the internalization of the IL-7 receptor.

PMID- 14636897
TI  - IL-4-dependent CD86 expression requires JAK/STAT6 activation and is negatively
      regulated by PKCdelta.
AB  - CD86 expression is up-regulated in activated monocytes and macrophages by a
      mechanism that is not clearly defined. Here, we report that IL-4-dependent CD86
      expression requires activation of ERK1/2 and JAK/STAT6 but is negatively
      regulated by PKCdelta. PMA differentiated U937 monocytic cells when stimulated
      with IL-4 increased CD11b and CD86 expression by 52- and 98-fold, respectively.
      PMA+IL-4 treatment also induced a synergistic enhancement of ERK1/2 activation
      when compared to the effects of PMA and IL-4 alone. Use of the mitogen or
      extracellular kinase (MEK) inhibitor, PD98059, completely blocked up-regulation
      of CD11b and CD86 demonstrating the importance of MEK-activated ERK1/2. JAK
      inhibition with WHI-P154-abrogated IL-4-dependent CD11b and CD86 up-regulation
      and inhibited STAT6 tyrosine phosphorylation. Importantly, CD11b and CD86
      expression were not reliant on IL-4-dependent activation of phosphatidylinositol
      3'-kinase (PI 3-kinase). Blockade of PKCdelta activation with rottlerin prevented
      CD11b expression but lead to a 75- and 213-fold increase in PMA and PMA+IL-4
      dependent CD86 expression, respectively. As anticipated, increasing PKCdelta
      activity with anti-sense reduction of CD45 increased CD11b expression and reduced
      CD86 expression. Likewise, rottlerin prevented nuclear localization of activated
      PKCdelta. We conclude from these data that IL-4-dependent CD11b expression relies
      predominantly on enhanced activation of ERK1/2, while IL-4-dependent CD86
      expression utilizes the JAK/STAT6 pathway.

PMID- 14636899
TI  - Quantitative parameters of image quality in multidetector spiral computed
      tomographic coronary imaging with submillimeter collimation.
AB  - Multidetector computed tomography (MDCT) permits visualization of the coronary
      arteries, but limited spatial and temporal resolution can lead to artifacts. We
      quantitatively evaluated the image quality that can be obtained with the latest
      generation of MDCT scanners with submillimeter collimation and increased gantry
      rotation speed. Thirty patients with angiographically proved absence of
      significant coronary artery stenoses (mean age 56 +/- 13 years, mean heart rate
      62 +/- 13 beats/min) were studied by MDCT (12 x 0.75 mm collimation, 420-ms tube
      rotation, 210-ms temporal resolution, 500 mA, 120 kVp, retrospective
      electrocardiographic gating). In multiplanar reconstructions of the 4 major
      coronary arteries (left main, left anterior descending, left circumflex, and
      right coronary artery), the overall visualized vessel length and the length of
      segments without motion artifacts were measured. Vessel diameters at 8 predefined
      locations were measured in MDCT maximum intensity projections and in
      corresponding invasive angiograms. The mean lengths of visualized coronary
      arteries were left main 13 +/- 6 mm, left anterior descending 138 +/- 39 mm, left
      circumflex 84 +/- 34 mm, and right coronary artery 155 +/- 41 mm. On average, 93
      +/- 13% of the total visualized vessel length was depicted without motion
      artifacts (left main 100 +/- 0%, left anterior descending 93 +/- 12%, left
      circumflex 91 +/- 17%, and right coronary artery 87 +/- 14%). The percentage of
      vessel length visualized free of motion artifacts was significantly higher in
      patients with a heart rate </=60 beats/min compared with patients with a heart
      rate >60 beats/min (96 +/- 8% vs 89 +/- 17%, p <0.05). Vessel diameters in MDCT
      correlated closely to quantitative coronary angiography (R(2) 0.83 to 0.87). In
      conclusion, MDCT with submillimeter collimation and improved temporal resolution
      permits reliable visualization of the vessel lumen and accurate measurements of
      vessel dimensions.

PMID- 14636900
TI  - Prognostic value of myocardial viability recognized by low-dose dobutamine
      echocardiography in chronic ischemic left ventricular dysfunction.
AB  - This study assesses the prognostic value of myocardial viability recognized as a
      contractile response to inotropic stimulation in patients with left ventricular
      (LV) dysfunction in a large-scale prospective, multicenter, observational study.
      Four hundred twenty-five patients (mean age 61 +/- 10 years) with
      angiographically proven coronary artery disease, previous (>3 months) myocardial
      infarction, and severe LV dysfunction (ejection fraction <35%; mean 28 +/- 6%)
      were enrolled in the study. Each patient underwent low-dose dobutamine
      echocardiography (up to 10 microg/kg/min). Myocardial viability was identified as
      a rest-stress variation (Delta) in the wall motion score index (WMSI), in which
      each segment was scored from 1 = normal to 4 = dyskinetic in a 16-segment model
      of the left ventricle. Myocardial viability was identified as an improvement of
      >/=0.40 in WMSI. All patients were followed for a median of 3.1 years. One
      hundred eighty-eight were revascularized either by coronary artery bypass
      grafting (n = 118) or coronary angioplasty (n = 70). The only end point analyzed
      was cardiac death. In the revascularized group, cardiac death occurred in 4 of
      the 52 patients with and in 37 of the 136 patients without myocardial viability
      (7.7% vs 27.2%, p <0.003). Kaplan-Meier survival estimates showed a better
      outcome for those patients with compared to patients without myocardial viability
      who underwent coronary revascularization (90.1% vs 62%, p <0.0078). Thus, in
      severe LV ischemic dysfunction, myocardial viability by low-dose dobutamine
      echocardiography is associated with improved survival in revascularized patients.

PMID- 14636901
TI  - Long-term prognosis after normal dobutamine stress echocardiography.
AB  - Patients with normal dobutamine stress echocardiography (DSE) were shown to have
      a favorable outcome at an intermediate-term follow-up. However, there are scarce
      data regarding long-term survival after normal DSE. This study sought to assess
      the long-term outcome after normal DSE. We studied 401 patients (age 62 +/- 10
      years, 264 men) who had a normal echocardiogram at rest and with high-dose
      dobutamine stress. End points during a mean follow-up of 5 +/- 1.7 years (minimum
      3.5) were all-cause mortality and hard cardiac events (cardiac death and nonfatal
      myocardial infarction). During follow-up, 45 patients (11%) died due to various
      causes (cardiac death in 10 patients). Thirteen patients had nonfatal myocardial
      infarction (a total of 23 hard cardiac events). The annual mortality rate was 2%
      in the first 3 years and 2.4% between the fourth and sixth years. The annual hard
      cardiac event rate was 0.8% in the first 3 years and 1.7% between the fourth and
      sixth years. Predictors of mortality in a multivariate analysis model were
      advanced age (hazard ratio 1.2, 95% confidence interval CI 1.1 to 1.4) and higher
      heart rate at rest (hazard ratio 0.92, 95% confidence interval 0.85 to 0.99).
      Patients with normal DSE had excellent outcomes during the 3 years after the
      study. The cardiac event rate was higher between the fourth and sixth year;
      therefore, it may be useful to repeat the study after 3 years to reassess risk
      status.

PMID- 14636902
TI  - Influence of depression and effect of treatment with sertraline on quality of
      life after hospitalization for acute coronary syndrome.
AB  - Major depressive disorders complicate recovery from acute coronary syndrome in
      approximately 1 in 5 patients, and have been found to be associated with
      significant impairments of quality of life and functioning. The aim of the
      present analysis was to evaluate the efficacy of sertraline in improving quality
      of life and functioning in patients diagnosed with major depression who had
      recently been hospitalized for acute coronary syndrome. Three hundred sixty-nine
      patients hospitalized in the previous month for acute coronary syndrome
      (myocardial infarction, 74%; unstable angina, 26%) who also met criteria for
      major depressive disorder were randomized to 24 weeks of double-blind treatment
      with sertraline (50 to 200 mg/day) or placebo. Quality-of-life and functional
      status were assessed using the Quality of Life, Enjoyment, and Satisfaction scale
      (Q-LES-Q) and the Medical Outcomes Study SF-36. Data from the total sample, and
      the recurrent depression subgroup, were analyzed. Severe baseline impairment was
      found in the Q-LES-Q and all subscales of the SF-36. A multivariate regression
      analysis identified depression as the strongest predictor of baseline quality-of
      life impairment (partial r, -0.37, p = 0.001). In the recurrent depression group,
      treatment with sertraline resulted in significantly greater improvement than
      placebo in the Q-LES-Q total score and SF-36 mental component summary score, as
      well as the SF-36 role limitations, emotional, and mental health factors.
      Depression has a substantial negative impact on quality of life and functioning
      in patients hospitalized for acute coronary syndrome. Sertraline was associated
      with clinically meaningful improvement in multiple quality-of-life domains in
      patients with acute coronary syndrome and recurrent depression.

PMID- 14636903
TI  - Depression as a risk factor for mortality after acute myocardial infarction.
AB  - The ENRICHD clinical trial, which compared an intervention for depression and
      social isolation to usual care, failed to decrease the rate of mortality and
      recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation
      for this is that depression was not associated with increased mortality in these
      patients. The purpose of this study was to determine if depression was associated
      with an increased risk of mortality in a subsample of the ENRICHD trial's
      depressed patients compared with a group of nondepressed patients recruited for
      an ancillary study. Three hundred fifty-eight depressed patients with an acute
      AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the
      ENRICHD medical inclusion criteria were followed for up to 30 months. There were
      47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk
      factors, depressed patients were at higher risk for all-cause mortality (hazard
      ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent
      infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with
      nondepressed patients. In conclusion, depression was an independent risk factor
      for death after AMI, but it did not have a significant effect on mortality until
      nearly 12 months after the acute event, nor did it predict nonfatal recurrent
      infarction.

PMID- 14636904
TI  - Relation of hemoglobin A1c to rate of major adverse cardiac events in nondiabetic
      patients undergoing percutaneous coronary revascularization.
AB  - Abnormalities in plasma glucose below the "diabetic range" of glycemia are
      associated with increased cardiovascular morbidity and mortality in patients
      without diabetes mellitus. The purpose of this study was to investigate the
      relation between ambient glycemic levels as measured by hemoglobin A1c and
      outcome after elective percutaneous coronary intervention (PCI). Baseline
      laboratory studies, including hemoglobin A1c, were drawn in 500 consecutive
      patients before elective PCI. Nondiabetic patients were defined as those without
      a history of diet or pharmacologically controlled diabetes mellitus and a
      hemoglobin A1c level <7.0%. Of the 500 patients studied, 291 (59%) were
      nondiabetic patients. Abnormal hemoglobin A1c levels (6% to 7%) were found in 30%
      of nondiabetic patients. Nondiabetic patients with an abnormal hemoglobin A1c
      level had a significantly higher rate of major adverse cardiac events (33% vs
      22%, p = 0.04), target vessel revascularization (31% vs 19%, p = 0.02), and
      cardiovascular mortality (4.6% vs 0.5%, p = 0.03) compared with nondiabetic
      patients with hemoglobin A1c levels <6%. Multivariate analysis disclosed that a
      hemoglobin A1c level of 6% to 7% was a significant independent predictor of major
      adverse cardiac events, target vessel revascularization, and cardiovascular
      mortality 12 months after PCI in nondiabetic patients. These data demonstrate
      that an abnormal hemoglobin A1c level may have prognostic significance in
      nondiabetic patients who undergo PCI.

PMID- 14636905
TI  - Comparison of rosuvastatin versus atorvastatin in patients with heterozygous
      familial hypercholesterolemia.
AB  - Heterozygous familial hypercholesterolemia (HFH) is a common genetic disorder
      that confers a significantly increased risk of early coronary artery disease.
      This study compared atorvastatin and rosuvastatin in reducing low-density
      lipoprotein (LDL) cholesterol in HFH in a global, 18-week, weighted
      randomization, double-blind, parallel-group, forced-titration study. Following a
      6-week diet lead-in, 623 patients were randomized to 20 mg/day of atorvastatin (n
      = 187) or rosuvastatin (n = 436) with forced titration at 6-week intervals to 80
      mg/day. The primary end point was percentage change in LDL cholesterol from
      baseline to week 18. At week 18, rosuvastatin therapy produced a significantly
      greater reduction in LDL cholesterol than atorvastatin (-57.9% vs -50.4%; p
      <0.001) and a significantly greater increase in high-density lipoprotein (HDL)
      cholesterol (12.4% vs 2.9%; p <0.001). Rosuvastatin also produced significantly
      greater reductions in apolipoprotein-B and all 4 major lipid ratios, as well as a
      significantly greater increases in apolipoprotein A-I (all p <0.001). More
      patients with HFH with coronary artery disease achieved the National Cholesterol
      Education Program Adult Treatment Panel III goal of LDL cholesterol <100 mg/dl
      (<2.6 mmol/L) on rosuvastatin 40 and 80 mg than atorvastatin 80 mg (17%, 24%, and
      4.5%, respectively). High-sensitivity C-reactive protein median values were
      reduced by 33% to 34% in both the 80-mg rosuvastatin- and atorvastatin-treated
      groups. Both treatments were well tolerated. Thus, in HFH, rosuvastatin force
      titrated from 20 to 80 mg/day produced significantly greater reductions than
      atorvastatin 20 to 80 mg/day in LDL cholesterol and improvements in HDL
      cholesterol and other lipid parameters, and enabled more patients to achieve LDL
      cholesterol goals.

PMID- 14636906
TI  - Relation of heart rate at rest and mortality in the Women's Health and Aging
      Study.
AB  - Increased heart rate (HR) has been shown to be associated with increased risk of
      all-cause and heart disease mortality. However, HR as a health indicator in
      disabled older women has not been closely examined. The purpose of this study is
      to assess the association between HR and 3-year mortality in disabled older
      women. HR at rest was measured using the electrocardiogram. Three groups were
      categorized by baseline HR (beats per minute): (1) <60, (2) 60 to 89, and (3)
      >/=90. The survival rate over 3 years was examined. For the total population, age
      adjusted 3-year mortality was nearly 40% for the HR >/=90 group, compared with
      <20% mortality in the HR 60 to 89 group. Women with a HR <60 beats/min had
      similar mortality to those with HRs 60 to 89 beats/min. Among women with no heart
      disease and normal electrocardiograms, mortality was slightly lower in all
      groups, but the association of elevated HR with increased mortality remained. In
      Cox proportional hazard models, after adjustment for age, number of diseases,
      medications, blood pressure, smoking status, body mass index, ankle-brachial
      index, activity status, physical performance score, and forced expiratory volume
      in the first second, there remained a twofold increase in the risk of death for
      the HR >/=90 group. Subclinical conditions not measured in this study, such as
      mild heart failure, may be associated with both increased HR and mortality; this
      may explain the relation. In patients with and without heart disease, further
      investigation of cardiovascular status may be warranted if their HR is >/=90
      beats/min.

PMID- 14636907
TI  - Impact of chronic kidney disease and anemia on hospitalization expense in
      patients with left ventricular dysfunction.
AB  - To estimate the independent effects of kidney disease, anemia, and the treatment
      effects of angiotensin-converting enzyme (ACE) inhibitors on hospitalization cost
      in patients with heart failure, we used data from the prevention and treatment
      trials of the Studies of Left Ventricular Dysfunction trial and retrospectively
      estimated the relative effects of decreased kidney function, as measured by
      estimated glomerular filtration rate (GFR) at enrollment, and anemia, as measured
      by hematocrit levels at enrollment, on hospital utilization and expense.
      Independent of the effects of age, gender, New York Heart Association (NYHA)
      class, ejection fraction, and the presence of diabetes mellitus, GFR was
      significantly related to hospitalization expense (percent change in
      hospitalization expense -16.8%, 95% confidence interval [CI] -11.9% to -21.5%)
      for GFR >/=90 ml/min/1.73 m(2) compared with GFR <60 ml/min/1.73 m(2)).
      Similarly, hematocrit levels were significantly related to hospitalization
      expense (percent change in hospitalization expense -19.9%, 95% CI -10.2% to 
      28.6%) for hematocrit >/=36% compared with hematocrit <33%). The beneficial
      effect of the ACE inhibitor enalapril was significantly related to
      hospitalization expense independent of the effects of GFR and hematocrit (percent
      change in hospitalization expense -6.8%, 95% CI -3.6% to -9.9% for treatment vs
      the placebo group), and the beneficial effect was preserved when independently
      estimated for subgroups with decreased kidney function. Adjusted mean expense per
      patient per month (PPPM) in the enalapril group was $708 versus $792 in the
      placebo group. Comparing survivors, enalapril generated annual cost savings
      greater than the average wholesale price of the drug at Studies of Left
      Ventricular Dysfunction mean dosage levels. Adjusted expected hospitalization
      expense varied from $636 PPPM for patients in the lowest hematocrit-GFR risk
      class (hematocrit >/=36%, GFR >/=90 ml/min/1.73 m(2)) to $1,127 PPPM for those in
      the highest risk class (hematocrit <33%, GFR <60 ml/min/1.73 m(2)). For patients
      who survived with reduced kidney function and anemia, ACE inhibitor therapy with
      enalapril reduced hospitalization expense more than the additional expense of the
      drug therapy. Thus, kidney disease and anemia are independent risk factors for
      hospitalization cost in patients with heart failure, and the beneficial effect of
      ACE inhibitors on hospitalization expense appears to be preserved within kidney
      disease and anemia subgroups.

PMID- 14636908
TI  - Impact of a preoperative mitral regurgitation scoring system on outcome of
      surgical repair for mitral valve prolapse.
AB  - The optimal timing of surgical correction of severe mitral regurgitation (MR) is
      important for improved morbidity and mortality. We utilized a scoring system to
      decide the timing of procedures. Based on clinical features and echocardiographic
      data, we hypothesized that preoperative semi-quantitation of MR using this
      scoring system may be useful for predicting prognosis after repair. The MR score
      was composed of 6 parameters associated with disease severity (i.e., history of
      heart failure, atrial fibrillation, pulmonary hypertension, left ventricular end
      systolic dimension, fractional shortening, and left atrial dimension). The
      maximum score was 6. Of 267 patients who underwent mitral valve repair in the
      last 10 years, 191 patients with mitral valve prolapse were studied. Patients
      were categorized into 2 groups according to MR score (group low [L] : 0 to 2.5
      and group high [H]: >/=3.0) irrespective of New York Heart Association functional
      class. A significant difference in postoperative event-free survival was observed
      between both groups (p = 0.0014); the adjusted risk ratio was 3.4 (95% confidence
      interval 1.6 to 7.2). Postoperative echocardiography showed larger left
      ventricular systolic dimensions (p <0.0001), lower fractional shortening (p =
      0.0016), and larger left atrial dimensions (p <0.0001) in group H than group L.
      Thus, an MR score is a simple way to predict the prognosis of severe MR
      independently of subjective symptoms in patients undergoing mitral valve repair.

PMID- 14636909
TI  - Effects of cilostazol in patients with Raynaud's syndrome.
AB  - Raynaud's syndrome (RS), which is characterized by recurrent episodes of
      vasospasm with exposure to cold, may occur alone (primary RS) or in association
      with connective tissue diseases or other underlying conditions (secondary RS). We
      investigated the effect of cilostazol on vessel wall responses in RS. Patients
      were diagnosed (primary or secondary RS associated with connective tissue
      diseases) and randomized to placebo or cilostazol 100 mg twice daily for 6 weeks
      in a double-blind manner. Brachial artery vasoreactivity, laser Doppler
      fluxmetry, and cold pressor testing (CPT) were performed at study initiation and
      completion. Symptoms were assessed using standardized questionnaires. Forty
      subjects completed the study (19 with primary RS and 21 with secondary RS).
      Cilostazol significantly increased the mean brachial artery diameter at 6 weeks
      (primary RS, p = 0.006; secondary RS, p = 0.06). There was no change in median
      flow-mediated dilation (FMD) with cilostazol in primary RS (25th, 75th
      percentiles) (4.06% [2.5, 6.1] to -0.77% [-2.4, 3.4] or secondary RS (2.2% [0.05,
      6.3] to 2.95% [1.7, 7.4]). There were no changes in nitroglycerin-mediated
      dilation or microvascular flow indexes in either cohort. In patients with primary
      RS, cilostazol treatment yielded a positive change in the slope of brachial
      responsiveness to CPT (increase of 0.32 mm/min; p = 0.002 vs placebo). Cilostazol
      treatment remained significantly associated with increased brachial artery
      diameter when controlling for baseline values (p = 0.018). Cilostazol increased
      conduit vessel diameter in patients with primary and secondary RS, with a
      favorable impact on conduit vessel responsiveness to cold in patients with
      primary RS without affecting microvascular flow or symptoms.

PMID- 14636910
TI  - Correlation between clinical findings and the "tombstoning" electrocardiographic
      pattern in patients with anterior wall acute myocardial infarction.
AB  - The tombstoning electrocardiographic pattern of a particular kind of ST-segment
      change, as observed in some patients during the early stages of acute myocardial
      infarction, is well known to be of prognostic value. However, little is
      understood of the causes and the relations of these changes. This study of 106
      patients showed that in patients with tombstoning electrocardiographic patterns,
      infarction size is larger; left ventricular ejection fraction and preinfact
      angina are lower, and in-hospital complications are higher.

PMID- 14636911
TI  - Usefulness of tachycardic-stress perfusion imaging to predict coronary artery
      disease in high-risk patients with chronic renal failure.
AB  - Uncertainty remains as to the most appropriate preoperative screening
      investigation to evaluate patient cardiac risk in prospective renal transplant
      recipients. We prospectively compared tachycardic-stress (exercise/pacing)
      scintigraphy with coronary angiography for the detection of significant coronary
      artery disease in this group. With a negative predictive value of 92%,
      tachycardic-stress scintigraphy may reduce the need for unnecessary coronary
      angiography in these patients.

PMID- 14636912
TI  - Usefulness of coronary flow reserve measured by transthoracic coronary Doppler
      ultrasound to detect severe left anterior descending coronary artery stenosis.
AB  - Transthoracic coronary Doppler ultrasound during venous adenosine infusion showed
      damped (<1) coronary flow velocity reserve in patients with severe left anterior
      descending coronary artery stenosis. Damped coronary flow reserve discriminated
      severe from nonsevere stenosis with high sensitivity, specificity, and positive
      predictive accuracy, and is a unique noninvasive tool to identify high-risk
      patients.

PMID- 14636913
TI  - Usefulness of shear stress pattern in predicting neointima distribution in
      sirolimus-eluting stents in coronary arteries.
AB  - The true 3-dimensional neointimal thickness distribution in sirolimus-eluting
      stents was investigated in relation to the shear stress distribution, which was
      obtained from computational fluid dynamics calculations. Small pits were observed
      between the stent struts in all patients, and a significant inverse relation
      between neointimal thickness and shear stress was found, indicating that deeper
      pits were present in the outside curve of the stented segments.

PMID- 14636914
TI  - Acute and long-term outcomes of cutting balloon angioplasty followed by gamma
      brachytherapy for in-stent restenosis.
AB  - In-stent restenosis lesions were divided into 2 groups according to the use of
      cutting balloon (n = 76) or conventional balloon angioplasty (n = 407) before
      gamma-brachytherapy. Cutting balloon angioplasty, compared with conventional
      balloon angioplasty, in patients undergoing gamma-brachytherapy for in-stent
      restenosis is associated with less requirement for new stents (11% vs 22%, p =
      0.02) but similar target vessel revascularization (35.1% vs 29.8%, p = 0.4) at
      follow-up.

PMID- 14636915
TI  - Effect of the PercuSurge GuardWire device on the integrity of microvasculature
      and clinical outcomes during primary transradial coronary intervention in acute
      myocardial infarction.
AB  - The present study investigates whether preintervention thrombectomy with a
      PercuSurge distal balloon protection device can improve final angiographic
      results compared with adjunctive tirofiban therapy during primary percutaneous
      coronary intervention (PCI) in large infarct-related arteries (IRAs) (vessel size
      >/=3.5 mm) with high-burden thrombus formation (HBTF). Results indicate that this
      mechanical device is superior to adjunctive tirofiban therapy during primary PCI
      in large IRAs with HBTF in terms of final epicardial flow, microvasculature
      integrity, and 30-day clinical outcomes.

PMID- 14636916
TI  - Relation of dietary fat and fiber to elevation of C-reactive protein.
AB  - We examined the relation of dietary fiber, fat, and other dietary factors to
      levels of highly sensitive C-reactive protein (CRP) in 4,900 adult participants
      in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES 99
      00), which was a cross-sectional study of a nationally representative sample of
      noninstitutionalized United States residents. After controlling for demographic
      factors, body mass index, smoking, alcohol consumption, exercise, and total
      caloric intake, subjects in the third and fourth highest quartiles of fiber
      consumption had a lower risk of elevated CRP (odds ratio [OR] 0.64, 95%
      confidence interval [CI] 0.43 to 0.96; OR 0.58, 95% CI 0.38 to 0.88,
      respectively) compared with the lowest quartile. Saturated fat consumption was
      modestly associated with elevated CRP (third quartile: OR 1.58, 95% CI 1.02 to
      2.44; fourth quartile 1.44, 95% CI 0.80 to 2.58). The findings suggest that
      inflammation may link dietary fiber and fat to cardiovascular disease.

PMID- 14636917
TI  - Effect of baseline levels on response of high-density lipoprotein cholesterol to
      hypolipidemic treatment.
AB  - The response of high-density lipoprotein cholesterol to hypolipidemic monotherapy
      with diet, statins, fibrates, or nicotinic acid was investigated prospectively in
      801 patients with dyslipidemia. We hypothesized that the behavior of high-density
      lipoprotein cholesterol after treatment would depend on its baseline levels and
      the therapy used.

PMID- 14636918
TI  - Prevention of atrial fibrillation recurrence by statin therapy in patients with
      lone atrial fibrillation after successful cardioversion.
AB  - The aim of this study was to investigate the effect of statin therapy on
      arrhythmia recurrence in patients with lone atrial fibrillation (AF). From July
      1998 to December 1999, 62 patients with lone persistent AF lasting >/=3 months
      underwent successful external cardioversion. After a mean follow-up of 44 months,
      85% had recurrence of AF. The use of statins was associated with a significant
      decrease in the risk of arrhythmia recurrence after successful cardioversion of
      AF. The result of this retrospective study demonstrates that the use of statins
      in patients with lone AF was associated with a significant decrease in the risk
      of arrhythmia recurrence after successful cardioversion.

PMID- 14636919
TI  - Reproducible efficacy of loading oral propafenone in restoring sinus rhythm in
      patients with paroxysmal atrial fibrillation.
AB  - This is the first study to demonstrate the reproducibility of an oral propafenone
      loading dose in converting paroxysmal atrial fibrillation in patients without
      significant cardiac disease or hypertension. This finding may support the
      development of the "pill-in-the-pocket" treatment strategy in this group of
      patients.

PMID- 14636920
TI  - Tissue velocity Doppler assessment of atrial and ventricular electromechanical
      coupling and atrioventricular time intervals in normal subjects.
AB  - Mechanical events and electromechanical coupling are analyzed simultaneously in
      the atria and ventricles using tissue velocity imaging. Normal values for these
      parameters are provided.

PMID- 14636921
TI  - Predicting survival in ambulatory patients with severe heart failure on beta
      blocker therapy.
AB  - Peak VO(2) and the Heart Failure Survival Score are 2 clinical parameters used to
      risk stratify patients with heart failure and time listing for cardiac
      transplantation. The efficacy of these prognostic variables in patients receiving
      beta-blocker therapy was evaluated.

PMID- 14636922
TI  - Circadian variation of death from congestive heart failure after prior myocardial
      infarction in patients >60 years of age.
AB  - In the present prospective study, there was a circadian pattern in the number of
      deaths per hour in patients with congestive heart failure after prior myocardial
      infarction. The primary peak occurred between 6 A.M. and 12 P.M., with 202 of 517
      deaths (39%) occurring in that 6-hour period.

PMID- 14636923
TI  - Value of parasternal long-axis vena contracta width for predicting severity of
      aortic regurgitation in left ventricular systolic dysfunction.
AB  - Correlations derived for the relations between parasternal long-axis vena
      contracta width and effective regurgitant orifice area, regurgitant volume, and
      regurgitant fraction were highly significant. A vena contracta width of <3.0 or
      >5.0 mm provided excellent specificity for nonsevere and severe aortic
      regurgitation, respectively.

PMID- 14636924
TI  - Prevalence and clinical profile of troponin T mutations among patients with
      hypertrophic cardiomyopathy in tuscany.
AB  - The prevalence and clinical profile of cardiac troponin T gene mutations were
      evaluated in 150 consecutive patients with hypertrophic cardiomyopathy from the
      well-defined geographic region of Tuscany. Troponin T mutations had a low
      prevalence (3.3%; including a newly described Phe110Leu mutation) and were
      associated with heterogeneous clinical expression and outcome.

PMID- 14636925
TI  - Effects of increased concentrations of glucose on platelet reactivity in healthy
      subjects and in patients with and without diabetes mellitus.
AB  - Hyperglycemia has been linked to adverse outcomes after myocardial infarction. We
      characterized the effect of selected concentrations of glucose or mannitol on
      platelet function in whole blood samples from healthy volunteers and from
      patients with and without diabetes mellitus. Activation of platelet glycoprotein
      IIb/IIIa and P-selectin expression was increased similarly after addition of
      isosmotic concentrations of glucose and mannitol, suggesting that increased
      osmolarity associated with hyperglycemia increases platelet reactivity.

PMID- 14636926
TI  - Comparison of survival in patients with pulmonary hypertension associated with
      fenfluramine to patients with primary pulmonary hypertension.
AB  - To test whether the clinical presentation and prognosis of fenfluramine-induced
      pulmonary hypertension (PH) differs from primary PH (PPH), we compared the
      clinical profile and outcome of 10 patients with fenfluramine-induced PH with
      that of 70 patients with PPH referred to our center over the same time frame and
      treated identically. Patients with diet pill PH were similar to those with PPH
      with respect to hemodynamics. However, patients with fenfluramine-induced PH had
      poorer survival: 1-year survival 50% versus 88%, and 3-year survival 17% versus
      60%.

PMID- 14636927
TI  - Usefulness of B-type natriuretic peptide as a noninvasive screening tool for
      cardiac allograft pathology in pediatric heart transplant recipients.
AB  - We examined the utility of B-type natriuretic peptide (BNP) in the evaluation of
      pediatric orthotopic heart transplant recipients for allograft pathology by
      measuring the serum BNP levels at the time of either screening echocardiography
      and biopsy, or at the time of clinical rejection. There was a significant
      difference (p <0.0001) in the BNP levels in 37 patients in the group with
      evidence of pathology compared with those without evidence. There was also 100%
      sensitivity and 100% negative predictive value of BNP levels >100 pg/ml for
      identifying graft pathology.

PMID- 14636928
TI  - Clinical and echocardiographic characteristics of hemodynamically significant
      pericardial effusions in patients with systemic lupus erythematosus.
AB  - Echocardiographic-guided pericardiocentesis was found to be safe and efficacious
      in treating 11 patients with systemic lupus erythematosus who had hemodynamically
      significant pericardial effusions. These patients tended to present early in
      their disease course, and men were more often affected.

PMID- 14636929
TI  - Echocardiographic determination of mean pulmonary artery pressure.
AB  - We performed a simultaneous Doppler and invasive study to validate the role of
      Doppler-derived peak pulmonary regurgitant velocity as a reliable noninvasive
      measure of pulmonary artery mean pressure. Assessment of right atrial pressure,
      as shown in this study, enhances the use of this Doppler parameter as a correlate
      of pulmonary artery mean pressure.

PMID- 14636932
TI  - Keeping abortion legal: a look beyond Roe v. Wade.

PMID- 14636933
TI  - The benefits and risks of over-the-counter availability of levonorgestrel
      emergency contraception.
AB  - Removing the prescription requirement for Plan B will help ensure that the
      product plays a larger role nationally in the reduction of unintended pregnancy
      and abortion-important public health goals. Over-the-counter (OTC) sale of Plan B
      should present no serious safety issues. OTC consumers are able to understand and
      follow the instructions for proper use of Plan B. Efficacy of the OTC product is
      likely to be the same as, or better than, the prescription product, given more
      timely access to treatment. Based on the results of a growing body of literature
      and foreign marketing experience, the risk of unintended health consequences also
      appears to be minimal. There is no evidence to suggest that American women will
      abuse Plan B as an OTC product.

PMID- 14636934
TI  - Nonlatex vs. latex male condoms for contraception: a systematic review of
      randomized controlled trials.
AB  - This systematic review sought to evaluate nonlatex male condoms in comparison
      with latex condoms in terms of contraceptive efficacy, breakage, slippage, safety
      and user preferences. We searched computerized databases and contacted
      manufactures and investigators to find randomized controlled trials of nonlatex
      vs. latex male condoms. Two reviewers independently abstracted data from the 10
      identified trials. While the eZ. on condom did not protect against pregnancy as
      well as its latex comparison condom, no differences were found in typical-use
      efficacy between the Avanti and the Standard Tactylon and their latex
      counterparts. Nonlatex condoms were associated with higher rates of clinical
      breakage than their latex comparisons, with statistically significant odds ratios
      of clinical breakage ranging from 2.6 (95% confidence interval [CI]: 1.6-4.3) to
      5.0 (95% CI: 3.6-6.8). Few adverse events were reported. Substantial proportions
      of participants reported preferences for the nonlatex condoms. Despite higher
      rates of clinical breakage, nonlatex condoms still provide an acceptable
      alternative for those with allergies, sensitivities or preferences that might
      prevent the consistent use of latex condoms. The contraceptive efficacy of
      nonlatex condoms requires more research.

PMID- 14636935
TI  - A consensus process to adapt the World Health Organization selected practice
      recommendations for UK use.
AB  - The nominal group technique for consensus development was used to consider the
      World Health Organization Selected Practice Recommendations for Contraceptive Use
      for adoption or adaptation in the United Kingdom. The nominal group comprised 11
      opinion leaders who agreed that 74% of the WHO recommendations were consistent
      with current UK practice. Of 63 recommendations considered by the group to be at
      odds with current practice, 23 were adopted with advice that United Kingdom
      practice should change in line with WHO. Twenty-five were adopted because,
      although the group felt that the WHO recommendation differed from practice in the
      UK, it was unable to reach a consensus on an alternative recommendation. Thirteen
      WHO recommendations underwent minor revision for UK use. The group rejected two
      further WHO recommendations [on the timing of starting low-dose progestogen-only
      contraception (POC) during lactation] but was unable to reach consensus on any
      alternative guidance. It was agreed clinicians should be left to decide for
      themselves how to advise breastfeeding women about when to start low-dose POC. A
      UK version of the WHO Selected Practice Recommendations should help to
      standardize practice and improve the quality of care for couples using
      contraception.

PMID- 14636936
TI  - A pilot study of mifepristone in combination with sublingual or vaginal
      misoprostol for medical termination of pregnancy up to 63 days gestation.
AB  - Of the total women included in the study, 96 women chose to receive misoprostol
      600 microg sublingually while 53 women received misoprostol 800 microg vaginally
      36-48 h after receiving mifepristone 200 mg. Complete abortion occurred in 93
      women (98.9%) in the sublingual and 51 women (96.2%) in the vaginal group (p =
      0.27). The mean induction-to-abortion interval was 3.2 h (SD = 1.4) in the
      sublingual and 4.1 h (SD = 1.5) in the vaginal group (p = 0.02). The mean
      gestation at abortion in weeks was 7.1 (SD = 1.0) in the sublingual and 7.7 (SD =
      1.3) in the vaginal group (p = 0.003). Women in the sublingual group experienced
      more vomiting (p = 0.03), diarrhea (p = 0.02) and unpleasant taste in their mouth
      (p = 0.0001) while those in the vaginal group experienced more headache (p =
      0.002). Of women in the sublingual group, 77% were satisfied with the route of
      misoprostol administration compared to 68% in the vaginal group (p = 0.25). These
      findings now need to be assessed in the context of a randomized controlled trial.

PMID- 14636937
TI  - Detection of raised FSH levels among older women using depomedroxyprogesterone
      acetate and norethisterone enanthate.
AB  - The objective of this study was to investigate whether follicle-stimulating
      hormone (FSH) levels can be used reliably to indicate approaching menopause in
      older (aged 40-49), long-term users of depomedroxyprogesterone acetate (DMPA) and
      norethisterone enanthate (NET-EN). One-hundred and seventeen women using DMPA, 60
      NET-EN users and 161 nonusers of contraception were recruited. At recruitment,
      serum FSH levels were measured and questions were asked regarding menopausal
      symptoms, menstrual cycle and date of last injection. Results of the recruitment
      blood test showed that 32% of the nonusers had FSH levels in the menopausal range
      >25.8 mIU/mL compared to 28% of the DMPA users and 9% of the NET-EN group. After
      adjusting for age, there was no significant difference between the 3 groups (p =
      0.13). An increase of 1 year in age increased the FSH level by 3 mIU/mL (p <
      0.001). All the hormonal contraceptive users were between 1 day and 12 weeks of
      their injection interval. Many had been using the injectable contraceptive method
      for over 10 years and almost all were amenorrheic at the time of recruitment. The
      data show that a raised FSH level can be detected during use of DMPA and NET-EN
      and could be used as a menopausal indicator without interrupting method use in
      this group of contraceptive users.

PMID- 14636938
TI  - Treating incomplete abortion in El Salvador: cost savings with manual vacuum
      aspiration.
AB  - When manual vacuum aspiration (MVA) was introduced to treat incomplete abortion
      at a regional training hospital in El Salvador, this study evaluated the impact
      of replacing sharp curettage with MVA. Hospital cost, length of hospital stay,
      complication rates and postabortion contraceptive acceptance were compared in a
      prospective, nonrandomized, controlled study of 154 women assigned to either
      traditional sharp curettage services or MVA services plus contraceptive
      counseling. Assignment depended on availability of trained providers. Compared to
      sharp curettage, use of MVA and associated changes in protocol led to a
      significant cost savings of 13% and shorter hospital stay of 28%. Dedicated
      family-planning counseling resulted in a threefold higher rate of contraceptive
      acceptance. Although the difference in cost was significant, much higher savings
      could be realized if minimal postoperative stays were implemented for both
      procedures. Barriers to early discharge include patient expectations, physician
      attitudes and training and hospital systems administration.

PMID- 14636939
TI  - Cost savings of manual vacuum aspiration for endometrial sampling in El Salvador.
AB  - Despite the existence of less costly and less invasive techniques to evaluate
      abnormal uterine bleeding, sharp curettage continues to be the most common form
      of endometrial sampling in the less developed world. Because manual vacuum
      aspiration (MVA) equipment is often associated with abortion care in countries
      where abortion is illegal, many practitioners have been slow to incorporate its
      use for other gynecological conditions. In this study, MVA was introduced in a
      large teaching hospital in El Salvador as an alternative for patients with
      abnormal uterine bleeding. Hospital cost, length of stay and complication rates
      were compared in a prospective, nonrandomized controlled study of 163 patients
      assigned to either traditional sharp curettage or MVA services. Patients were
      assigned to each group depending on the availability of trained providers.
      Methodologies for cost-savings analysis were modified to obtain more precise cost
      estimates. Use of MVA was associated with a significant cost savings of 11% and a
      hospital stay that was 27% shorter as compared to sharp curettage. Cost savings
      could be much higher if MVA was institutionalized as an ambulatory procedure with
      minimal or no preoperative evaluation and postoperative stay.

PMID- 14636940
TI  - An assessment of the quality of information available on the internet about the
      IUD and the potential impact on contraceptive choices.
AB  - This study analyzed data gathered from a survey of online information on the
      intrauterine device (IUD) to determine the content and quality of information
      available to consumers and providers, as evidenced by the presence or absence of
      a series of attributes measuring the accuracy and objectiveness of information
      provided. While information on the IUD is consistently available on websites
      providing information about birth control options, there is a great deal of
      misinformation about the IUD on the Internet. A substantial percentage of sites,
      designed for both healthcare providers and consumers, state that the IUD
      increases risk of pelvic inflammatory disease, ectopic pregnancy and infertility.
      This misinformation can effectively limit access to the IUD, so it is vital to
      monitor the quality of information available to consumers online and encourage
      clinicians to take an active role in correcting misperceptions among their
      patients.

PMID- 14636941
TI  - Feasibility study of the use of a daily electronic mail reminder to improve oral
      contraceptive compliance.
AB  - Women who ingest their oral contraceptive pill (OCP) as part of a daily routine
      are more likely use their OCPs correctly. This trial examines the feasibility of
      an electronic-mail (e-mail) reminder system to improve OCP compliance. An e-mail
      reminder was sent to 50 new OCP users daily for 3 months. Subjects sent an e-mail
      reply to confirm receipt. OCP compliance was recorded on diaries. Four subjects
      were discontinued for not checking their e-mail. Active participants missed a
      median of 18% of the e-mail reminders (range: 0-65%). A follow-up visit was
      scheduled after completion of three OCP cycles. Of the 40 subjects returning
      completed diaries, 50% missed no active pills at all and 20% missed at least one
      in each cycle. Most found the daily e-mail somewhat (65%) or very helpful (19%)
      for OCP compliance. Of those continuing OCPs, 64% wanted to continue receiving e
      mail reminders at the completion of the study. Because inconsistent OCP use is a
      significant cause of unplanned conception, the use of e-mail to improve OCP
      compliance has the potential to decrease unintended pregnancies.

PMID- 14636942
TI  - Miscommunication between healthcare providers and patients may result in
      unplanned pregnancies.
AB  - Our objective was to examine the impact of prior healthcare provider counseling
      on previous use of contraception and knowledge of emergency contraception in
      women seeking surgical abortion. We performed a retrospective analysis of 342
      patient charts from women seeking an office abortion in a private practice
      setting from January 1999 to June 2001. Data extracted included demographic
      information, primary method of contraception over the preceding few months,
      compliance with that method, contraceptive history, knowledge of emergency
      contraception and postabortion contraception. Patients were primarily white (69%)
      and unmarried (63%) and had private insurance that covered abortion services
      (72%). Only 19% of women were using a birth control method with no recognized
      potential failure. Twenty-two percent of women were using their birth control
      method correctly but experienced an event that put them at risk for pregnancy,
      32% were using their birth control method incorrectly and 27% were using no birth
      control method at all. Miscommunication between patients and their healthcare
      provider(s) negatively affected use of a primary contraceptive method in 14% of
      patients. Of the 77% of women who did not know about emergency contraception,
      nearly two thirds had an identifiable event for which emergency contraception
      could have been used. Healthcare providers may contribute to the occurrence of
      unintended pregnancy if they provide poor medical advice or miscommunicate with
      patients.

PMID- 14636943
TI  - Reproductive health counseling at pregnancy testing: a pilot study.
AB  - OBJECTIVES: To pilot brief reproductive health counseling for women obtaining
      pregnancy testing in a managed-care setting who did not desire pregnancy.
      METHODS: Women received counseling, access to contraception and a booster call at
      2 weeks. Changes in contraceptive behavior were evaluated. RESULTS: Of 85 women
      who completed counseling, 58 (68%) completed follow-up. Participants reported
      that counseling was useful at baseline (94%) and follow-up (83%). The staff found
      the intervention important (100%) and implementation feasible (100%). Forty-one
      percent of participants improved their use of contraception (from no use or from
      less effective use to more effective use). Twenty-nine percent continued highly
      effective use and 9% recessed from highly effective use. Of 22 participants with
      risk of sexually transmitted disease, 3 (14%) began using condoms consistently,
      while 1 (5%) continued using condoms consistently. CONCLUSIONS: Counseling at
      pregnancy testing was well accepted by the staff and participants. Observed
      behavioral changes suggest that this intervention may be effective in increasing
      effective use of contraception.

PMID- 14636944
TI  - Adolescent beliefs about infertility.
AB  - PURPOSE: Explore adolescents' definition of fertility and range of beliefs
      regarding causes of infertility. METHODS: Qualitative study involving five focus
      groups that met between April 2001 and December 2001 at a hospital-based
      adolescent health center. All groups were led by one experienced moderator and
      observed by two investigators. Audiotapes of the group discussions were
      transcribed and reviewed independently by three investigators who met and reached
      consensus on underlying themes. RESULTS: Most adolescents generally understood
      fertility as the ability to become pregnant. Ten themes emerged as causes of
      infertility. Anatomic/gynecologic causes generated the most responses and most
      detailed discussion (e.g., "The coating on the egg is too hard and the sperm
      can't get in to fertilize the egg."). Other commonly mentioned causes were male
      factors (e.g., "He cannot produce sperm."), sexually transmitted infections
      (e.g., "like chlamydia caused scarring in the fallopian tubes"), genetics
      (e.g.,"a birth defect") and substance use (e.g., "if a man smoke weed all day,
      the egg may not develop because of problems with his sperm"). Less commonly
      mentioned themes were stress, contraception, environmental toxins, violence and
      injury. CONCLUSIONS: Most adolescents defined fertility as the ability to become
      pregnant and reported an extensive range of beliefs about the causes of
      infertility. Providers should consider eliciting adolescents' definitions of
      fertility and also exploring beliefs about causes of infertility with their
      patients when counseling about sexuality and contraception to determine if an
      adolescent has inaccurate beliefs about their fertility.

PMID- 14636945
TI  - Phagocytosis of apoptotic cells and the resolution of inflammation.
AB  - Clearance of apoptotic cells by phagocytic cells plays a significant role in the
      resolution of inflammation, protecting tissue from harmful exposure to the
      inflammatory and immunogenic contents of dying cells. Apoptosis induces cell
      surface changes that are important for recognition and engulfment of cells by
      phagocytes. These changes include alterations in surface sugars, externalization
      of phosphatidylserine and qualitative changes in the adhesion molecule ICAM-3.
      Several studies have contributed to clarify the role of the receptors on the
      surface of phagocytes that are involved in apoptotic cell clearance. The
      phagocytic removal of apoptotic cells does not elicit pro-inflammatory responses;
      in contrast, apoptotic cell engulfment appears to activate signals that suppress
      release of pro-inflammatory cytokines. Therefore, clearance of apoptotic
      leucocytes is implicated in the resolution of inflammation and mounting evidence
      suggests that defective clearance of apoptotic cells contributes to inflammatory
      and autoimmune diseases. Defining the ligands on apoptotic cells and the
      corresponding receptors on phagocytes with which they engage, is likely to lead
      to the development of novel anti-inflammatory pro-resolution drugs. In this
      article, we will review the recognition and signaling mechanisms involved in the
      phagocytosis of apoptotic cells as well as the role of endogenous compounds that
      play a relevant role in the modulation of inflammation. We will also discuss what
      is currently known about diseases that may reflect impaired phagocytosis and the
      consequences on inflammation and immune responses.

PMID- 14636946
TI  - In situ identification of protein structural changes in prion-infected tissue.
AB  - Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative
      disorders characterized by the conversion of the normal prion protein (PrP(C))
      into aggregates of its pathological conformer (PrP(Sc)). The mechanism behind
      this structural conversion is unclear. We report the identification of disease
      related protein structural differences directly within the tissue environment.
      Utilizing a synchrotron infrared (IR) light source, IR images of protein
      structure were obtained at a subcellular resolution, revealing regions of
      decreased alpha-helical content and elevated beta-sheet structure in and around
      infected neurons in the 263 K scrapie hamster model. PrP(Sc) immunostaining of
      the same tissue demonstrated that the elevated beta-sheet regions correspond to
      regions where the misfolded structure of PrP(Sc) is located. No evidence of these
      structural changes was observed in normal neurons.

PMID- 14636947
TI  - Akt/PKB kinase phosphorylates separately Thr212 and Ser214 of tau protein in
      vitro.
AB  - Microtubule-associated protein tau contains a consensus motif for protein kinase
      B/Akt (Akt), which plays an essential role in anti-apoptotic signaling. The motif
      encompasses the AT100 double phospho-epitope (Thr212/Ser214), a specific marker
      for Alzheimer's disease (AD) and other neurodegenerations, raising the
      possibility that it could be generated by Akt. We studied Akt-dependent
      phosphorylation of tau protein in vitro. We found that Akt phosphorylated both
      Thr212 and Ser214 in the longest and shortest tau isoforms as determined using
      phospho site-specific antibodies against tau. Akt did not phosphorylate other tau
      epitopes, including Tau-1, AT8, AT180, 12E8 and PHF-1. The Akt-phosphorylated tau
      retained its initial electrophoretic mobility. Immunoprecipitation studies with
      phospho-specific Thr212 and Ser214 antibodies revealed that only one of the two
      sites is phosphorylated per single tau molecule, resulting in tau immunonegative
      for AT100. Mixed kinase studies showed that prior Ser214 phosphorylation by Akt
      blocked protein kinase A but not GSK3beta activity. On the other hand, GSK3beta
      selectively blocked Ser214 phosphorylation, which was prevented by lithium. The
      results suggest that Akt may be involved in AD-specific phosphorylation of tau at
      the AT100 epitope in conjunction with other kinases. Our data suggest that
      phosphorylation of tau by Akt may play specific role(s) in Akt-mediated anti
      apoptotic signaling, particularly relevant to AD and other neurodegenerations.

PMID- 14636948
TI  - Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation
      and aquaporin 4 expression in lupus cerebritis.
AB  - Changes in brain water and cerebral volume can lead to brain edema that may be
      one of the underlying causes of death in many neurological diseases. Cerebral
      water content is regulated by aquaporin 4 (AQ4) present in astrocytic end feet
      and around blood vessels. In systemic lupus erythematosus (SLE), magnetic
      resonance imaging (MRI) studies of the brain have demonstrated lesions with the
      prominent appearance of edema. Activation of complement may play a significant
      role in the pathogenesis of lupus cerebritis by causing inflammation that can
      lead to edema. In this study, the well-established MRL/lpr lupus mouse model was
      used to evaluate the role of complement in lupus cerebritis. IgG and C1q
      colocalized in perivascular deposits indicating that the blood-brain barrier was
      compromised. Both RNA and protein expressions of AQ4 were significantly increased
      in brains of MRL/lpr mice. Chronic administration of the soluble complement
      inhibitor, Crry-Ig, reduced inflammation as measured by decreased accumulation of
      IgG. In contrast to control MRL/lpr mice, AQ4 expression in complement inhibited
      MRL/lpr mice was not changed relative to untreated congenic controls. These
      results illustrate that complement activation in brains of lupus mice leads to
      enhanced AQ4 expression and inflammation. It is conceivable that increased AQ4
      expression results in cerebral edema and hence complement inhibition may provide
      a new therapeutic option in inflammatory cerebral disorders such as lupus
      cerebritis.

PMID- 14636949
TI  - N-acetylcysteine prevents intra-acinar oxygen free radical production in
      pancreatic duct obstruction-induced acute pancreatitis.
AB  - Although oxygen free radicals (OFR) are considered to be one of the
      pathophysiological mechanisms involved in acute pancreatitis (AP), the
      contribution of acinar cells to their production is not well established. The aim
      of the present study was to determine the effect of N-acetylcysteine (NAC) in the
      course of AP induced by pancreatic duct obstruction (PDO) in rats, directly
      analysing by flow cytometry the quantity of OFR generated in acinar cells. NAC
      (50 mg/kg) was administered 1 h before and 1 h after PDO. Measurements by flow
      cytometry of OFR generated in acinar cells were taken at different PDO times over
      24 h, using dihydrorhodamine-123 as fluorescent dye. Histological studies of
      pancreas and measurements of neutrophil infiltration in the pancreas, pancreatic
      glutathione (GSH), malondialdehyde (MDA) levels, plasma amylase activity and
      hemoconcentration were carried out in order to assess the severity of AP at
      different stages. NAC effectively blunted GSH depletion at early AP stages and
      prevented OFR generation found in acinar cells as a consequence of AP induced by
      PDO. This attenuation of the redox state impairment reduced cellular oxidative
      damage, as reflected by less severe pancreatic lesions, normal pancreatic MDA
      levels, as well as diminished neutrophil infiltration in pancreas.
      Hyperamylasemia and hemoconcentration following AP induction were ameliorated by
      NAC administration at early stages, when oxidative stress seems to be critical in
      the development of pancreatitis. In conclusion, NAC reinforces the antioxidant
      defences in acinar cells, preventing OFR generation therefore attenuating
      oxidative damage and subsequently reducing the severity of PDO-induced AP at
      early stages of the disease.

PMID- 14636950
TI  - Thyroid hormones stimulate calcium transport systems in rat intestine.
AB  - Thyroid hormone status influences calcium metabolism. To elucidate the mechanism
      of action of thyroid hormones on transcellular transport of calcium in rat
      intestine, Ca(2+) influx and efflux studies were carried out in brush border
      membrane vesicles (BBMV) and across the basolateral membrane (BLM) of
      enterocytes, respectively. Steady-state uptake of Ca(2+) into BBMV as well as
      Ca(2+) efflux from the BLM enterocytes was significantly increased in
      hyperthyroid (Hyper-T) rats and decreased in hypothyroid (Hypo-T) rats as
      compared to euthyroid (Eu-T) rats. Kinetic studies revealed that increase in
      steady state Ca(2+) uptake into BBMV from hyper-T rats was fraternized with
      decrease in Michaelis Menten Constant (K(m)), indicating a conformational change
      in Ca(2+) transporter. Further, this finding was supported by significant changes
      in transition temperature and membrane fluidity. Increased Ca(2+) efflux across
      enterocytes was attributed to sodium-dependent Ca(2+) exchange activity which was
      significantly higher in Hyper-T rats and lower in Hypo-T rats as compared to Eu-T
      rats. However, there was no change in Ca(2+)-ATPase activity of BLMs of all
      groups. Kinetic studies of Na(+)/Ca(2+) exchanger revealed that alteration in
      Na(+)-dependent Ca(2+) efflux was directly associated with maximal velocity
      (V(max)) of exchanger among all the groups. cAMP, a potent activator of
      Na(+)/Ca(2+) exchanger, was found to be significantly higher in intestinal mucosa
      of Hyper-T rats as compared to Eu-T rats. Therefore, the results of this study
      suggest that Ca(2+) influx across BBM is possibly modulated by thyroid hormones
      by mediating changes in membrane fluidity. Thyroid hormones activated the
      Na(+)/Ca(2+) exchange in enterocytes possibly via cAMP-mediated pathway.

PMID- 14636951
TI  - Endomorphins, endogenous opioid peptides, provide antioxidant defense in the
      brain against free radical-induced damage.
AB  - Oxidative stress has been considered to be a major cause of cellular injuries in
      a variety of chronic health problems, such as carcinogenesis and
      neurodegenerative disorders. The brain appears to be more susceptible to
      oxidative damage than other organs. Therefore, the existence of antioxidants may
      be essential in brain protective systems. The antioxidative and free radical
      scavenging effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous
      opioid peptides in the brain, have been investigated in vitro. The oxidative
      damage was initiated by a water-soluble initiator 2,2'-azobis(2-amidinopropane
      hydrocholoride) (AAPH) and hydrogen peroxide (H2O2). The linoleic acid
      peroxidation, DNA and protein damage were monitored by formation of
      hydroperoxides, by plasmid pBR 322 DNA nicking assay and single-cell alkaline
      electrophoresis, and by SDS-polyacrylamide gel electrophoresis. Endomorphins can
      inhibit lipid peroxidation, DNA strand breakage, and protein fragmentation
      induced by free radical. Endomorphins also reacted with galvinoxyl radicals in
      homogeneous solution, and the pseudo-first-order rate constants were determined
      spectrophotometrically by following the disappearance of galvinoxyl radicals. In
      all assay systems, EM1 was more potent than EM2 and GSH, a major intracellular
      water-soluble antioxidant. We propose that endomorphins are one of the protective
      systems against free radical-induced damage in the brain.

PMID- 14636952
TI  - Human paraoxonase gene cluster polymorphisms as predictors of coronary heart
      disease risk in the prospective Northwick Park Heart Study II.
AB  - The anti-atherogenic effect of HDL has been suggested to be partly due to the
      action of HDL-associated paraoxonase (PON). Three distinct enzymes have been
      identified, encoded by PON1, PON2 and PON3, clustered on chromosome 7q21-q22. Two
      cSNPs in PON1 (L55M and Q192R) and one in PON2 (S311C) have been implicated as
      independent risk factors for coronary heart disease (CHD) in some, but not all,
      studies. A PON3 SNP (A99A) was identified and the effect of these four PON SNPs
      on HDL levels and CHD risk was examined in the prospective Northwick Park Heart
      Study II (NPHSII). Genotype frequencies did not differ between cases and controls
      but the CHD risk associated with smoking was significantly modified by PON1 L55M
      genotype. Compared to LL non-smokers, LL smokers had a hazard ratio (HR) of 1.30
      (95% CI 0.81-2.06) while M-allele carriers had a HR of 1.76 (1.17-2.67). When
      genotypes were analysed in combination, men with the genotype PON1 55 LM/MM+PON2
      311 CC, had HR of 3.54 (1.81-6.93) compared to PON1 LL+PON2 SS/SC men
      (interaction P=0.004). These effects were independent of classical risk factors.
      These data demonstrate the importance of stratifying by environmental factors and
      the use of multiple SNPs for genetic analysis.

PMID- 14636953
TI  - P-glycoprotein-mediated multidrug resistance phenotype of L1210/VCR cells is
      associated with decreases of oligo- and/or polysaccharide contents.
AB  - Multidrug resistance of murine leukaemic cell line L1210/VCR (obtained by
      adaptation of parental drug-sensitive L1210 cells to vincristine) is associated
      with overexpression of mdr1 gene product P-glycoprotein (Pgp)-the ATP-dependent
      drug efflux pump. 31P-NMR spectra of L1210 and L1210/VCR cells (the latter in the
      presence of vincristine) revealed, besides the decrease of ATP level, a
      considerable lower level of UDP-saccharides in L1210/VCR cells. Histochemical
      staining of negatively charged cell surface binding sites (mostly sialic acid) by
      ruthenium red (RR) revealed a compact layer of RR bound to the external coat of
      sensitive cells. In resistant cells cultivated in the absence or presence of
      vincristine, the RR layer is either reduced or absent. Consistently, resistant
      cells were found to be less sensitive to Concanavalin A (ConA). Moreover,
      differences in the amount and spectrum of glycoproteins interacting with ConA
      Sepharose were demonstrated between sensitive and resistant cells. Finally, the
      content of glycogen in resistant cells is lower than in sensitive cells. All the
      above facts indicate that multidrug resistance of L1210/VCR cells mediated
      predominantly by drug efflux activity of Pgp is accompanied by a considerable
      depression of oligo- and/or polysaccharides biosynthesis.

PMID- 14636954
TI  - Sulfation patterns in heparin and heparan sulfate: effects on the proliferation
      of bovine pulmonary artery smooth muscle cells.
AB  - Heparin's (HP's) antiproliferative effect on smooth muscle cells is potentially
      important in defining new approaches to treat pulmonary hypertension. The
      commercially available HP and heparan sulfate (HS) are structurally heterogenous
      polymers. In order to examine which sulfonate groups are required for endogenous
      antiproliferative activity, we prepared the following six chemically modified
      porcine mucosal HP and HS, which fell into three groups. One group consisted of
      fully O-sulfonated-N-acetylated, the second group consisted of de-N-sulfonated
      and re-N-acetylated, and the third group consisted of 6-O-desulfonated HP and HS
      derivatives. These six preparations were assayed for their antiproliferative
      potency on bovine pulmonary artery smooth muscle cells. The results of this assay
      show that (a) over-O-sulfonation of both HP and HS increases antiproliferative
      activity, (b) substitution of hexosamine with N-acetyl diminishes
      antiproliferative activity in both HP and HS, and (c) 6-O-desulfonation of HP and
      HS diminishes antiproliferative potency. Surprisingly, the type of uronic acid
      residue present at a given level of sulfation is unimportant for
      antiproliferative potency. In conclusion, only the level of O- and N-sulfo group
      substitution correlates well with HP and HS antiproliferative activity.

PMID- 14636955
TI  - Inhibition of brain energy metabolism by the alpha-keto acids accumulating in
      maple syrup urine disease.
AB  - Neurological dysfunction is a common finding in patients with maple syrup urine
      disease (MSUD). However, the mechanisms underlying the neuropathology of brain
      damage in this disorder are poorly known. In the present study, we investigated
      the effect of the in vitro effect of the branched chain alpha-keto acids (BCKA)
      accumulating in MSUD on some parameters of energy metabolism in cerebral cortex
      of rats. [14CO(2)] production from [14C] acetate, glucose uptake and lactate
      release from glucose were evaluated by incubating cortical prisms from 30-day-old
      rats in Krebs-Ringer bicarbonate buffer, pH 7.4, in the absence (controls) or
      presence of 1-5 mM of alpha-ketoisocaproic acid (KIC), alpha-keto-beta
      methylvaleric acid (KMV) or alpha-ketoisovaleric acid (KIV). All keto acids
      significantly reduced 14CO(2) production by around 40%, in contrast to lactate
      release and glucose utilization, which were significantly increased by the
      metabolites by around 42% in cortical prisms. Furthermore, the activity of the
      respiratory chain complex I-III was significantly inhibited by 60%, whereas the
      other activities of the electron transport chain, namely complexes II, II-III,
      III and IV, as well as succinate dehydrogenase were not affected by the keto
      acids. The results indicate that the major metabolites accumulating in MSUD
      compromise brain energy metabolism by blocking the respiratory chain. We presume
      that these findings may be of relevance to the understanding of the
      pathophysiology of the neurological dysfunction of MSUD patients.

PMID- 14636956
TI  - Participation of the opioid system in cannabinoid-induced antinociception and
      emotional-like responses.
AB  - Several anatomical, biochemical and pharmacological evidence support the
      existence of bidirectional interactions between cannabinoid and opioid systems.
      The present review is focused on the participation of the endogenous opioid
      system in the antinociceptive and emotional-like responses induced by
      cannabinoids, and the development of tolerance to cannabinoid pharmacological
      effects. Cannabinoid and opioid agonists produce antinociception by acting on
      similar structures within the central nervous system, and a peripheral mechanism
      has been also proposed for both compounds. Pharmacological studies have suggested
      that the endogenous opioid system could be involved in cannabinoid
      antinociception and the development of cannabinoid tolerance. Recent studies
      using knockout mice have also demonstrated the role of the opioid system in
      cannabinoid antinociception and tolerance, although some discrepancies with the
      previous pharmacological results have been reported when using knockout mice. On
      the other hand, cannabinoid administration can induce anxiolytic-like responses
      that are mediated at least in part by an endogenous opioid activity on micro- and
      delta-opioid receptors.

PMID- 14636957
TI  - Molecular mechanisms of tolerance to and withdrawal of GABA(A) receptor
      modulators.
AB  - Here, we summarize recent data pertaining to the effects of GABA(A) receptor
      modulators on the receptor gene expression in order to elucidate the molecular
      mechanisms behind tolerance and dependence induced by these drugs. Drug
      selectivity and intrinsic activity seems to be important to evidence at the
      molecular level the GABA(A) receptor tolerance. On the contrary, we suggested
      that all drug tested are equally potentially prone to induce dependence. Our
      results demonstrate that long-lasting exposure of GABA(A) receptors to endogenous
      steroids, benzodiazepines and ethanol, as well as their withdrawal, induce marked
      effects on receptor structure and function. These results suggest the possible
      synergic action between endogenous steroids and these drugs in modulating the
      functional activity of specific neuronal populations. We report here that
      endogenous steroids may play a crucial role in the action of ethanol on
      dopaminergic neurons.

PMID- 14636958
TI  - Drug dependence and the endogenous opioid system.
AB  - The discovery of endogenous opioids has markedly influenced the research on the
      biology of drug dependence. Evidence has been presented that these brain
      substances are self-administered by laboratory animals. This finding, among
      others, has led to the hypothesis that endogenous opioids are involved in
      reinforcing habits, including dependence on drugs of abuse. The course of drug
      dependence is presented as a continuum from no drug use via controlled use to an
      actual dependence on the drug. Specific brain opioid systems belonging to four
      conceptualized brain circuits are described to be involved during the different
      phases of the drug dependence continuum. More recent research to delineate the
      role of endogenous opioid systems in drug dependence has focussed on genetic
      research in humans and animals. Among others, the findings obtained from studies
      of opioid receptor and opioid peptide precursor knockout mice provided further
      support for a role of endogenous opioid systems in drug dependence, in agreement
      with previous pharmacological studies.

PMID- 14636959
TI  - The impact of stress on addiction.
AB  - This article will review data obtained from both clinical and preclinical
      investigations demonstrating that exposure to stress has a significant impact on
      drug addiction. The preclinical literature suggests that stress increases reward
      associated with psychomotor stimulants, possibly through a process similar to
      sensitization. While it is not conclusive that a similar process occurs in
      humans, a growing clinical literature indicates that there is a link between
      substance abuse and stress. One explanation for the high concordance between
      stress-related disorders and drug addiction is the self-medication hypothesis,
      which suggests that a dually diagnosed person often uses the abused substance to
      cope with tension associated with life stressors or to relieve symptoms of
      anxiety and depression resulting from a traumatic event. However, another
      characteristic of self-administration is that drug delivery and its subsequent
      effects on the hypothalamo-pituitary-adrenal (HPA) axis are under the direct
      control of the individual. This controlled activation of the HPA axis may result
      in the production of an internal state of arousal or stimulation that is actually
      sought by the individual (i.e., the sensation-seeking hypothesis). During
      abstinence, exposure to stressors or drug-associated cues can stimulate the HPA
      axis to remind the individual about the effects of the abused substance, thus
      producing craving and promoting relapse. Continued investigations into how stress
      and the subsequent activation of the HPA axis impact addiction will result in the
      identification of more effective and efficient treatment for substance abuse in
      humans. Stress reduction, either alone or in combination with pharmacotherapies
      targeting the HPA axis may prove beneficial in reducing cravings and promoting
      abstinence in individuals seeking treatment for addiction.

PMID- 14636960
TI  - Neuroadaptive mechanisms of addiction: studies on the extended amygdala.
AB  - A conceptual structure for drug addiction focused on allostatic changes in reward
      function that lead to excessive drug intake provides a heuristic framework with
      which to identify the neurobiologic neuroadaptive mechanisms involved in the
      development of drug addiction. The brain reward system implicated in the
      development of addiction is comprised of key elements of a basal forebrain
      macrostructure termed the extended amygdala and its connections.
      Neuropharmacologic studies in animal models of addiction have provided evidence
      for the dysregulation of specific neurochemical mechanisms not only in specific
      brain reward circuits (opioid peptides, gamma-aminobutyric acid, glutamate and
      dopamine) but also recruitment of brain stress systems (corticotropin-releasing
      factor) that provide the negative motivational state that drives addiction, and
      also are localized in the extended amygdala. The changes in the reward and stress
      systems are hypothesized to maintain hedonic stability in an allostatic state, as
      opposed to a homeostatic state, and as such convey the vulnerability for
      development of dependence and relapse in addiction.

PMID- 14636961
TI  - Brain imaging studies in human addicts.
AB  - Addiction provides fertile ground for the application of the tools of functional
      neuroimaging. They can be divided into studies of neural activity and
      neurotransmitter function. Using the former, both opiates and stimulants cause a
      global decrease in brain metabolism. Against this background, acute doses have
      still been shown to produce relative increases in brain activation in specific
      regions, e.g., anterior cingulate, thalamus, and amygdala. These are also regions
      frequently found with cue-exposure paradigms. Our own work on cue-exposure has
      shown that heroin-related stimuli provoke activation of the anterior cingulate
      and orbitofrontal regions. Brain metabolism has also been shown to increase in
      drug withdrawal from alcohol and cocaine. Neurotransmitter studies have shown
      that in alcohol dependence, GABA(A)-benzodiazepine (GABA-BDZ) receptors are
      reduced in a number of brain regions and suggest that there may be 'capacity
      within the system' in some benzodiazepine functions, but tolerance to others,
      e.g., time asleep. Finally, 11C-Ro15-4513 offers new opportunities for imaging
      the GABA-BDZ system.

PMID- 14636962
TI  - Dopamine mediation of positive reinforcing effects of amphetamine in stimulant
      naive healthy volunteers: results from a large cohort.
AB  - A positive experience during a first encounter with a drug of abuse is predictive
      of subsequent use and might represent a vulnerability factor to develop
      addiction. This paper presents a meta-analysis of data acquired in 60 healthy
      volunteers who underwent a low-dose amphetamine challenge (0.3 mg/kg, i.v.)
      during imaging of dopamine D2 receptor availability with SPECT and the D2/D3
      radiotracer [123I]IBZM. Amphetamine-stimulated DA release induced a small,
      significant and highly variable decrease in striatal D2 receptor availability (
      8.3 +/- 6.7%). The magnitude of the decrease in D2 receptor availability was
      significantly associated with the positive reinforcing effects of the drug
      reported by the subject (r2 = 0.14, p = 0.003). Age was associated with decreased
      potency of dopamine to elicit positive reinforcing effects. This study indicates
      that both a large dopaminergic response and young age during a first encounter
      with a drug of abuse potential contribute to higher positive reinforcing effects.

PMID- 14636963
TI  - Acamprosate and naltrexone treatment for alcohol dependence: an evidence-based
      risk-benefits assessment.
AB  - This paper provides an evidence-based risk-benefit assessment of acamprosate and
      naltrexone in the treatment of alcohol dependence. A risk-benefit assessment is
      based on the premise that the choice of treatment depends on a number of factors,
      notably the adverse event profile and efficacy. An evidence-based approach
      attempts to operationalize how such risk-benefit assessments are made to inform
      physician choices. This approach involves a systematic assessment of all
      published double-blind, placebo-controlled trials. Based on this review, we
      conclude acamprosate and naltrexone are both useful in the treatment of alcohol
      dependence. However, the two drugs act in different ways in the brain, and their
      clinical profiles are different. Treatment effects seem to be more reliable for
      acamprosate, and this drug is better tolerated. The safety of the two drugs in
      combination has been supported by two independent double-blind studies, and
      combination treatment may offer an advantage for some patients.

PMID- 14636964
TI  - Pharmacological treatments for heroin and cocaine addiction.
AB  - AIMS: To provide an overview of the pharmacological options for the treatment of
      heroin- and cocaine-dependent patients based on known biochemical pathways to
      addiction and the chronic disease model as a starting point for treatment
      planning. RESULTS: Recent pre-clinical and clinical studies indicate that
      different brain structures and different neurotransmitters are involved in
      different stages of the addiction process. In addition, clinical experience shows
      that heroin and cocaine addiction can best be conceptualised and treated as a
      chronic, relapsing disorder with the following treatment goals: crisis
      intervention, cure or recovery (detoxification, relapse prevention) and care or
      partial remission (stabilization and harm reduction). The various high-quality
      studies, systematic literature reviews and formal meta-analyses clearly
      demonstrate that today many proven effective interventions are available for
      crisis intervention, detoxification, stabilization and harm reduction for heroin
      dependent patients. Interventions directed at relapse prevention are still
      problematic and only effective in a minority of motivated patients in stable
      living conditions and adequate social support. In contrast, no proven effective
      pharmacological interventions are available for the treatment of cocaine
      dependent patients, maybe with the exception of some patient groups that seem to
      benefit from treatment with disulfiram or amantadine. Treatment innovations are
      primarily based on experimental animal studies. Newly developed cannabinoid
      receptor antagonists and cortisol synthesis inhibitors show great promise.
      CONCLUSION: Heroin addiction is a chronic relapsing disease that is difficult to
      cure, but stabilization and harm reduction can greatly increase the life time
      expectancy and the quality of life of the patient, his direct environment and
      society as a whole. Currently, no proven effective pharmacological interventions
      are available for cocaine addiction, and treatment has to rely on existing
      cognitive behaviour therapies combined with contingency management strategies.

PMID- 14636965
TI  - Injury risk associated with cannabis and cocaine use.
AB  - The purpose of this paper is to review the results and limitations of studies of
      injury risks associated with cannabis and cocaine use. Three types of fatal and
      non-fatal injuries are considered: injuries due to collisions, intentional
      injuries and injuries in general. Four types of studies were reviewed: (I)
      laboratory studies, (II) descriptive and analytic epidemiological studies on the
      prevalence of cannabis or cocaine use through drug testing of those injured,
      (III) studies of non-clinical samples, and (IV) studies of clinical samples of
      drug users. The research that utilized drug tests showed similar proportions
      testing positive for cannabis in fatal and non-fatal injury groups, and for
      collisions, violence and injuries in general. By contrast, large differences in
      the average proportions testing positive for cocaine were found among these same
      injury groups. For example, 28.7% of people with intentional injuries (primarily
      homicides) tested positive for cocaine, while 4.5% of injured drivers tested
      positive. Studies of non-clinical samples have shown that both cannabis and
      cocaine use are related to intentional injuries and injuries in general. Results
      indicate higher risk for all types of injuries among cannabis and cocaine clients
      in treatment. Strengths and limitations of the different types of studies are
      discussed. More rigorous studies are needed which should focus on ruling out
      alternative explanations for relationships between drug use and injuries.

PMID- 14636966
TI  - Substance use in a sample of Turkish medical students.
AB  - This study identifies the prevalence of smoking, alcohol, and illicit drug use in
      a sample of Turkish medical students. Information about substance use was
      obtained from 304 first-year, and 143 sixth-year medical students from three
      different medical schools in Turkey. Nearly half of the students (53.9%) were non
      drinkers. Risky alcohol use was 7.4%. Lifetime smoking prevalence was 39.9 and
      26.4% of the junior and 44.1% of the senior medical students (mean consumption of
      13.9 and 15.5 cigarettes a day, respectively) reported regular smoking. Nicotine
      dependence was present in 3.1%. Only 4% of the students reported using illicit
      drugs (cannabis, ecstasy, cocaine) at least once in their lifetime. The mean ages
      of first use of cigarettes, alcohol and illicit drugs were earlier for junior
      medical students than senior students. Of the students, 25.5% had anxiety and
      36.8% had depression scores in the clinically significant range. Our results
      suggest that although Turkish medical students are not at a high risk of
      substance abuse it should not be underestimated, and the risk factors as well as
      the protective factors must be identified in nation-wide studies.

PMID- 14636967
TI  - Predictors of attendance in a randomized clinical trial of nicotine replacement
      therapy with behavioral counseling.
AB  - Participant attendance at smoking cessation-counseling sessions is an important
      factor in treatment outcome. In this study, we examined the influence of
      demographic, psychological, and smoking history variables on attendance at a
      randomized clinical trial comparing transdermal nicotine and nicotine nasal spray
      that included seven sessions of behavioral group counseling. Of the 353
      participants, 70.5% attended all seven sessions. Perfect attendance predicted
      abstinence from cigarettes at the end of treatment and at 6-month follow-up. In a
      logistic regression model, higher levels of education and higher body mass index
      were significant independent predictors of better attendance. There was a
      significant interaction between type of nicotine replacement (transdermal
      nicotine vs. nasal spray) and sex: females were less likely than males to have
      perfect attendance in the nasal spray group, but there was no sex difference in
      attendance for the transdermal nicotine group. These findings suggest that
      smokers with lower body mass index and less formal education may benefit from
      proactive counseling to address individual barriers to attendance at smoking
      cessation counseling. Additional research in this area would also be valuable to
      evaluate strategies to promote attendance in these high-risk groups.

PMID- 14636968
TI  - Reduced cardiovascular effects of methamphetamine following treatment with
      selegiline.
AB  - Selegiline is a specific MAO-B inhibitor. As MAO-B has been shown to be
      significantly involved in the metabolism of dopamine in certain regions of the
      primate brain, selegiline has been proposed for use in the treatment of drug
      addiction. Selegiline is also metabolized in vivo to l-methamphetamine.
      Therefore, when given in combination with psychostimulants such as d
      methamphetamine, there is the potential for adverse effects. To study this
      possibility, squirrel monkeys were treated with chronic selegiline and tested
      with two doses of d-methamphetamine (0.1 and 1.0 mg/kg, i.v.). Following at least
      7 days of treatment with once daily 0.3 mg/kg i.m. selegiline, the effects of
      methamphetamine on blood pressure and heart rate were no different than the
      effects of methamphetamine observed prior to selegiline treatment. However,
      following at least 10 days of treatment with 1.0 mg/kg i.m. selegiline, the
      effects of methamphetamine on blood pressure and heart rate were significantly
      reduced. Both methamphetamine and amphetamine were detected in plasma following
      chronic selegiline treatment. When monkeys were given an acute selegiline
      injection prior to methamphetamine, reduced cardiovascular effects were also
      seen. These results indicate that selegiline can be used safely even in
      combination with methamphetamine, as the cardiovascular effects of the drug
      combination were no greater than either drug alone, and were actually reduced at
      the higher selegiline dose.

PMID- 14636969
TI  - Escalating morphine exposures followed by withdrawal in feline immunodeficiency
      virus-infected cats: a model for HIV infection in chronic opiate abusers.
AB  - Opiate abuse is a risk factor for human immunodeficiency virus (HIV) infection.
      Because the direct effects of opiates on HIV infection are difficult to determine
      epidemiologically, animal models of lentivirus infection are relied upon to study
      the effects of opiates in the absence of confounding factors. Morphine, the
      predominant metabolite of heroin, is used in most experimental systems examining
      heroin abuse. In this study, morphine treatment of feline immunodeficiency virus
      (FIV)-infected cats modeled a typical pattern of escalating drug use interspersed
      with withdrawals. Plasma cortisol levels were measured for evidence of stress
      associated with morphine withdrawal. In the morphine-treated cats, cortisol
      levels peaked at time points corresponding to morphine withdrawal and returned to
      baseline levels during treatment and several weeks after the final withdrawal.
      Morphine-treated cats displayed clear behavioral and physical signs of opiate
      exposure and evidence of withdrawal when the drug was stopped. Morphine-exposed
      cats did not experience enhanced severity of FIV-related disease; in fact,
      morphine demonstrated a protective effect on FIV-associated changes in brainstem
      auditory evoked potentials. Our research suggests that opiate exposure is
      unlikely to adversely affect the progression of acute lentivirus infection and
      might be beneficial in controlling associated neurological disease.

PMID- 14636970
TI  - Finding order in the DSM-IV nicotine dependence syndrome: a Rasch analysis.
AB  - Little is known about the relative severity or typical sequence of Diagnostic and
      Statistical Manual (DSM-IV) symptoms of nicotine dependence. Using data from the
      National Comorbidity Study (NCS), the current study used a Rasch logistic item
      response model to assess the unidimensionality of the construct of nicotine
      dependence, to identify which symptoms are associated with high levels of
      dependence, and to determine whether the dependence symptoms and typical symptom
      patterns are influenced by age, gender, race and income level. The nicotine
      dependence symptoms provided reasonable coverage of the dependence syndrome and
      can be used to scale individuals reliably. However, attention to potential
      demographic differences in responding to particular symptoms is needed.
      Furthermore, additional symptoms that describe behavioral changes that support
      continued smoking would be useful in helping to map the lower and higher ranges
      of dependence continuum. Evaluation of the typical pattern of responses to the
      nicotine dependence symptoms suggested that most smokers responded in a
      predictable manner. However, the tendency for younger smokers to provide more
      atypical responses than other smokers suggests a need to develop more specialized
      items for this population. More precise assessment of nicotine dependence would
      improve the predictive value of these measures and ultimately help inform
      nicotine dependence treatments.

PMID- 14636971
TI  - An independent assessment of MEDWatch reporting for abuse/dependence and
      withdrawal from Ultram (tramadol hydrochloride).
AB  - OBJECTIVE: Assess the validity of medical products reporting program (MEDWatch)
      reports of abuse/dependence and withdrawal associated with Ultram (tramadol).
      METHODS: Reports of possible abuse/dependence or withdrawal associated with
      Ultram during 13 quarters following launch were spontaneously reported to the
      manufacturer Ortho-McNeil Pharmaceutical (OMP) and also solicited from 255 NIDA
      grantees and addiction treatment professionals by an Independent Steering
      Committee (ISC). Reports were classified by the ISC using DSM-IV criteria, by the
      Drug Safety and Surveillance (DSS) units of Robert Wood Johnson Pharmaceutical
      Research Institute (PRI) using World Health Organization Adverse Reaction Terms
      (WHOART) terms, and reported to the food and drug administration (FDA) via
      MEDWatch. Rates of abuse/dependence and withdrawal per 100000 persons exposed
      were calculated separately for classifications made by the PRI and the ISC, and
      confidence intervals calculated to determine the degree to which they agreed.
      RESULTS: For 681 reports submitted to PRI, confidence intervals of ISC ratings
      contained PRI ratings 12 of 13 times for abuse/dependence, and 12 of 13 times for
      withdrawal. For 242 reports submitted to the ISC, confidence intervals of ISC
      ratings contained PRI ratings 10 of 13 times for abuse/dependence, and 12 of 13
      times for withdrawal. Proactive surveillance increased the total number of cases
      of abuse/dependence but not withdrawal. Many cases of withdrawal without signs or
      symptoms of abuse/dependence were identified. CONCLUSIONS: There was
      good/excellent concordance between MEDWatch and ISC classifications. Proactive
      surveillance increased cases of abuse/dependence but not withdrawal. Withdrawal
      with no signs or symptoms of dependence was common. More use of proactive
      surveillance is likely to improve assessments of public health risks associated
      with adverse events.

PMID- 14636972
TI  - The pharmacology of cocaethylene in humans following cocaine and ethanol
      administration.
AB  - BACKGROUND: Concurrent use of cocaine and alcohol results in formation of a
      cocaine homolog and metabolite-cocaethylene. METHODS: To characterize
      cocaethylene pharmacology, ten paid volunteer subjects were given deuterium
      labeled (d(5)) cocaine (0.3, 0.6, and 1.2 mg/kg and cocaine placebo) by a 15-min
      constant rate intravenous injection 1 h after a single oral dose of ethanol (1
      g/kg) or ethanol and cocaine placebo using a double-blind, crossover design. Six
      of the same volunteers subsequently received a 1.2 mg/kg dose of cocaine alone. A
      small (7.5 mg) nonpharmacologically active dose of deuterium-labeled cocaethylene
      d(3) was concurrently administered with the cocaine to enable calculation of
      absolute cocaethylene formation and clearance. Plasma and urine cocaine,
      cocaethylene, and benzoylecgonine concentrations, physiologic and subjective
      effects were measured. RESULTS: When co-administered with ethanol, 17+/-6%
      (mean+/-S.D.) of the cocaine was converted to cocaethylene. Cocaethylene peak
      plasma concentrations and AUC increased proportionally to the cocaine dose.
      Ethanol ingestion prior to cocaine administration decreased urine benzoylecgonine
      levels by 48% and increased urinary cocaethylene and ecgonine ethyl ester levels.
      Subjects liked and experienced more total intoxication after the combination of
      cocaine and ethanol than after either drug alone. CONCLUSIONS: In the presence of
      ethanol, the altered biotransformation of cocaine resulted in 17% of an
      intravenous cocaine dose being converted to cocaethylene and relatively lower
      urinary concentrations of benzoylecgonine.

PMID- 14636973
TI  - Item functioning of the alcohol dependence scale in a high-risk sample.
AB  - We conducted in-depth analyses of the functioning of items from the alcohol
      dependence scale (ADS) in a sample of high-risk alcohol drinkers, specifically
      101 men and 93 women mandated to a domestic violence intervention program. We
      first conducted a maximum likelihood common factors analysis on the ADS, which
      indicated a primarily unidimensional factor structure. We then used a
      nonparametric kernel smoothing method to create item characteristic curves (ICC)
      and option characteristic curves (OCC) for each ADS item. Based on these curves,
      we identified nine of the 25 ADS items as reliably discriminating between those
      with no or minimal alcohol problems and those with symptoms of excessive or
      abusive drinking. Dichotomous scoring appeared most appropriate for these items.
      No differential item functioning (DIF) by gender was detected, indicating that
      these items assess alcohol problems similarly in both men and women. This nine
      item empirically-derived abbreviation of the ADS appeared to be an efficient and
      effective measure in this sample; it was highly correlated with the original
      scale (r(s)=0.96) yet had superior distributional properties. Retained items
      reflected primarily excessive or hazardous drinking rather than alcohol
      dependence per se, suggesting that items targeting these types of symptoms may be
      most useful in high-risk samples. Combined with previous work with the ADS in
      treatment-seeking alcoholics, mapping of ADS item severities suggests a continuum
      of alcohol problem severity from heavy drinking to severe withdrawal that may be
      reliably tapped with dichotomous items.

PMID- 14636974
TI  - The effect of drugs of abuse on NMDAR1 receptor expression in the rat limbic
      system.
AB  - An increasing body of evidence points to the role of N-methyl-D-aspartate (NMDA)
      receptors in the limbic system in the mechanism of drug dependence. We studied
      the influence of acute and repeated morphine (20 mg/kg i.p. or increasing dose
      for 10 days) and cocaine (3x20 mg/kg i.p. per day at hourly intervals, for 1 or 5
      days) administration on the expression of glutamate NMDA receptor subunit 1
      (NMDAR1) in the central and basolateral nuclei of the rat amygdala and
      hippocampal formation. Acute or chronic morphine and cocaine administration
      increased NMDAR1 mRNA level in the central and basolateral nuclei of the
      amygdala; morphine did so 3 h after the last dose and 48 h after withdrawal,
      cocaine 3 h after acute and last chronic dose. Morphine did not change the NMDAR1
      mRNA level in the hippocampal formation, but chronic cocaine did decrease it in
      the dentate gyrus only. Our study suggests a possible link between the expression
      of NMDAR1 and changes in limbic system neuronal activity and behaviour after
      administration of morphine and cocaine. In summary, the present study
      demonstrated that morphine and cocaine influenced the expression of NMDAR1 in the
      structure of the limbic system which could be involved in dependence phenomena.

PMID- 14636975
TI  - Risky sexual behavior in relation to marijuana and alcohol use among African
      American, male adolescent detainees and their female partners.
AB  - This study examined substance use and risky sexual behavior (RSB) in a specific
      incident among 210 African-American, male adolescents who were being held in
      juvenile detention facilities. The participants completed a questionnaire that
      included four measures of substance use (i.e. alcohol and marijuana use by the
      participants and their partners), two measures of RSB (i.e. no prior discussion
      of sexual risks, condom nonuse) and six measures of potential correlates of
      sexual risk. Within-subjects analyses indicated participants and their partners
      were more likely to have used marijuana than alcohol during the sexual incident.
      Bivariate analyses indicated the participants' marijuana use was associated with
      no prior discussion of sexual risks and condom nonuse, and the partners'
      marijuana use was associated with no prior discussion of sexual risks. The
      association between participant marijuana use and condom nonuse, and the
      association between partner marijuana use and no prior discussion of sexual
      risks, also emerged in multivariate analyses that included the substance use
      variables and potential covariates. These findings suggest that marijuana use
      should be addressed in interventions that aim to prevent sexually transmitted
      diseases and unwanted pregnancies among adolescent detainees.

PMID- 14636976
TI  - Aspartic proteases from Plasmodium chabaudi: a rodent model for human malaria.
AB  - Intraerythrocytic malaria parasites degrade haemoglobin to provide nutrients for
      their own growth and maturation. Plasmodium aspartic proteases known as
      plasmepsins play an important role on haemoglobin degradation and are being
      studied as drug targets for chemotherapy of malaria. The rodent model for human
      malaria, Plasmodium chabaudi, is an experimentally good model for therapy drug
      design. The gene encoding an aspartic protease precursor (proplasmepsin) from the
      rodent malaria parasite P. chabaudi was cloned and sequenced. A theoretical 3D
      structure model was constructed by comparative homology and used for
      superimposition with other known models. Analysis of the P. chabaudi and
      Plasmodium yoelli genomes revealed in both the presence of at least seven
      plasmepsins and each one has sequence similarity to its plasmepsin counterpart of
      the human malaria Plasmodium falciparum. The predicted proteins were confirmed as
      plasmepsins by detection on Blocks Database of three characteristic blocks of the
      eukaryotic and viral aspartic protease family. Analysis of the proline-rich loop
      amino acid sequence of these plasmepsins suggests that they constitute
      characteristic motifs of each plasmepsin group suggesting that these sequence
      variations are related with different substrate specificities.

PMID- 14636977
TI  - On the increase of portal pressure during the acute and chronic phases of murine
      schistosomiasis mansoni and its reversibility after treatment with oxamniquine.
AB  - The purpose of the present study was to evaluate the effect of treatment with
      oxamniquine on the portal pressure of mice infected with Schistosoma mansoni. The
      animals were infected with 30 cercariae and portal pressure was measured with a
      polygraph at 70 (acute phase) and 160 (chronic phase) days after infection. On
      days 70 and 160 two other groups of infected mice were treated with 400 mg/kg of
      oxamniquine and portal pressure was measured 90 days later (160 and 250 days
      after infection). A group of uninfected mice was used as control. The measured
      portal pressures, in mmHg, were: matched uninfected control mice 8.7+/-2.1 and
      acute phase group, measured at day 70, 13.4+/-3.5. Matched uninfected control
      7.5+/-0.6 and chronic phase group, measured at day 160 post-infection, 11.6+/
      1.5. Matched uninfected mice 6.9+/-0.9 and chronic phase group, measured at day
      250, 10.4+/-1.8. Oxamniquine-treated at day 70 and measured at day 160 7.9+/-0.4;
      oxamniquine-treated at day 160 and measured at day 250, 7.6+/-1.7. The infection
      of mice with 30 cercariae of S. mansoni induced portal hypertension, both during
      the acute and chronic phases and treatment with oxamniquine caused portal
      pressure to return to normal levels.

PMID- 14636978
TI  - Risk factors for malaria infection and anemia for pregnant women in the Sahel
      area of Bandiagara, Mali.
AB  - Malaria infection and anemia during pregnancy are the primary causes of maternal
      and fetal morbidity and mortality. The aims of this study were to identify risk
      factors for malaria infection and to assess the relationship between malaria
      infection and anemia in pregnant women. Two cross-sectional surveys were
      conducted in September 1993 and then again in May 1994 (the end of the rainy and
      dry seasons respectively). A total of 235 pregnant women were randomly selected
      from both the rural and urban areas of Bandiagara, Mali. According to results
      from multivariate analysis, the risk of malaria infection was significantly
      higher during the rainy season (OR= 4.85, 95% CI 2.42-9.75) the first trimester
      of gestation (OR= 2.21, 95% CI 1.00-4.87, in younger women (OR= 2.48, 95% CI 1.19
      5.16), and in women living in the rural area (2.49, 95% CI 0.99-6.27). The risk
      of anemia was also higher during the rainy season (OR= 1.93, 95% CI 1.10-3.39, in
      the rural area (OR= 3.55, 95% CI 1.46-8.62). The risk of anemia was lower during
      the first trimester of gestational age (OR= 0.45, 95% CI 0.22-0.92). The
      relationship between malaria infection and anemia also varied with season. During
      the rainy season, the risk for anemia was similar among malaria-infected and non
      infected pregnant women. In contrast, the risk was higher among infected pregnant
      women during the dry season (OR= 3.43, 95% CI 1.09-10.07). In conclusion, the
      data suggest, that earlier gestation age, living in the rural area, and young age
      rather than parity are important risk factors for malaria infection in pregnant
      women. Further, malaria infection is strongly associated with anemia in pregnant
      women particularly during the dry season and is most likely the cause of anemia.
      Thus, control measures against malaria infection should target younger rural
      women in their first trimester of pregnancy.

PMID- 14636979
TI  - Sensitive and specific serodiagnosis of river blindness using Onchocerca ochengi
      antigens.
AB  - Despite the large-scale application of ivermectin for the treatment of human
      onchocerciasis, this filarial disease has remained a public health hazard,
      requiring rapid and sensitive diagnostic methods for more efficient management.
      Several serological methods based on homologous native or recombinant diagnostic
      antigens have been developed. However, these antigens have remained scarce in the
      endemic areas. We report herein the preparation and evaluation of an Onchocerca
      ochengi total worm extract together with its low molecular weight (< 31 kDa) and
      14.4 kDa antigens for the diagnosis of human onchocerciasis. The 14.4 kDa antigen
      and the low molecular weight antigen fraction were identified by Western blot
      experiments. The antigens were employed for the detection of IgG4 in sera of 43
      onchocerciasis patients, 35 normal Africans, 15 schistosomiasis patients, 11
      ascariasis patients, 9 loaisis patients and 3 healthy Europeans. The diagnostic
      specificity values were 94.5, 87.5 and 100%, while the sensitivities were 90.7,
      80 and 76.6% using the worm extract, low molecular weight antigen fraction and
      the 14.4 kDa antigen, respectively. We conclude that total worm extracts of O.
      ochengi can conveniently replace recombinant antigen cocktails in poor settings
      that do not have access to the latter.

PMID- 14636980
TI  - Prevention of alveolar echinococcosis--ecosystem and risk management perspectives
      in Japan.
AB  - We focused on the epidemiology of alveolar echinococcosis especially in Japan and
      discussed control measures to prevent an epidemic. No effective control measures
      against alveolar echinococcosis have been identified thus far because it is
      difficult to fully understand the ecology of the parasite and its hosts, i.e. the
      precise infection route to humans. In Hokkaido, Japan, infection rates among red
      foxes have recently risen even in low endemic districts. Infection seems to be
      spreading not only among wild foxes but also among domestic dogs. Despite only
      sporadic reports of human cases in Japan, we predict that the incidence of
      alveolar echinococcosis will increase in the near future if no effective
      preventive measures are put in place. An Echinococcus multilocularis epidemic
      would have the potential to affect the economy of Hokkaido, due to its impact on
      the agricultural and tourist industries. Well-designed epidemiological surveys
      are, therefore, urgently required prior to large outbreaks, based on
      understanding of the ecosystem around E. multilocularis.

PMID- 14636981
TI  - Evidence for continued two-brood replication of Plasmodium falciparum in vivo
      during quinine treatment.
AB  - To investigate the relationship between fever and parasite clearance in
      falciparum malaria, we studied 54 adults with Plasmodium falciparum infections
      who were all treated with quinine. The median oral temperature profile showed
      peaks at 24 h intervals during the first 3 days. Although there was no equivalent
      pattern evident in the median parasite clearance curve, we hypothesize that small
      numbers of two distinct parasite broods continued to develop in antiphase through
      schizogony despite quinine therapy. These data are consistent with previous
      reports of two dominant broods in untreated humans and monkeys infected with P.
      falciparum, and highlight the need for an adequate duration of quinine treatment.

PMID- 14636982
TI  - Randomised efficacy and safety study of two 3-day artesunate rectal
      capsule/mefloquine regimens versus artesunate alone for uncomplicated malaria in
      Ecuadorian children.
AB  - The combination of artesunate and mefloquine is one of the most effective
      treatments against multidrug-resistant falciparum malaria. Experience in children
      is however limited. The objective of this study was to compare the efficacy and
      safety of two artesunate/mefloquine combinations with artesunate monotherapy in
      Ecuadorian children. A total of 150 children with an age between 2 and 12 years,
      confirmed to have uncomplicated falciparum malaria, were randomly selected and
      divided in three treatment groups of 50 patients each. Group 1 received 50 mg
      rectal capsules alone (40 mg/kg total dose) administered over 6 days. Group 2
      received 50 mg rectal capsules (30 mg/kg total dose) for 3 days combined with
      mefloquine (20 mg/kg total dose) on day 1. Group 3 was treated with 50 mg rectal
      capsules (30 mg/kg total dose) for 3 days, combined with mefloquine on days 1 and
      3 (15-17 mg/kg total dose). Patients were continuously followed up and controlled
      by clinical and laboratory examinations for 7 days as well as on days 14, 21 and
      28. An additional parasite examination was performed at 2 months following
      therapy. Clearance of parasitaemia was comparable between treatment groups. These
      were 9.2, 9.2 and 8.3 h for Groups 1, 2 and 3, respectively. Cure rates at day 28
      were 76, 96 and 94% and after 2 months 60, 88 and 80%, respectively. There were
      no adverse events (AEs) reported during the study. Vital signs and laboratory
      examinations revealed no changes of clinical relevance. It can be concluded that
      the combination of artesunate rectal capsules with mefloquine is effective and
      safe. Starting concomitant administration already on day 1 is well tolerated.
      This combination significantly reduces the incidence of recrudescence compared to
      artesunate monotherapy. Comparing the two tested artesunate/mefloquine regimens,
      a total mefloquine dose of 20 mg/kg seems to be more effective compared to a
      total dose of 15-17 mg/kg. Further studies seem to be warranted.

PMID- 14636983
TI  - Impact of alphacypermethrin treated bed nets on malaria in villages of Malkangiri
      district, Orissa, India.
AB  - The impact of use of bed-nets treated with alphacypermethrin, at 20 mg (ai)/m2,
      in comparison to untreated nets or no nets on malaria vectors and malaria
      incidence was studied in tribal villages of Malkangiri district, Orissa state,
      India, which are highly endemic for falciparum malaria. Treated or untreated nets
      were supplied to the villagers in June 1999 and the nets were re-treated in
      September 1999, just before the rise in vector abundance and malaria incidence.
      The seasonal pattern of indoor resting Anopheles fluviatilis females was similar
      in all the three groups of villages before the start of intervention and the
      indoor resting catches were not significantly different between treatment-groups
      (two-way ANOVA, F = 1.53; d.f. = (2, 78); P = 0.2). During intervention, the
      indoor resting catches differed significantly among treatment groups (two-way
      ANOVA, F = 38.9; d.f.= (2, 66); P < 0.005). There was a 99% reduction in the
      indoor resting catches of An. fluviatilis in villages with treated nets and 61%
      reduction in villages with untreated nets compared with no-net villages.
      Comparison between villages with and without treated nets showed that there was
      97% reduction in indoor resting catches in villages with treated nets. Pair-wise
      comparison showed that the reductions between villages with and without nets as
      well as between villages with treated and untreated nets were significant
      (Dunnett's C-test, P < 0.05). The indoor resting catches of Anopheles
      culicifacies did not differ significantly among the three groups of villages
      either before (F = 0.99; d.f. = (2, 121); P = 0.4) or during intervention (F =
      0.21; d.f. = (2, 66); P = 0.8). Bioassay with 3 min exposure to treated bed nets
      showed 100% mortality of An. culicifacies for 2 months and with An. fluviatilis
      for 4.5 months after which tests were not carried out. In villages with treated
      nets, the Annual Parasite Incidence (API) significantly declined (P < 0.05) by
      about 65.7% and prevalence of infection among children (< 15 years) declined by
      57.1%, whereas in villages with untreated nets, there was only 34% reduction in
      API and 13% in the prevalence of infection. In villages with treated nets, there
      was 48% reduction in API and 64% in prevalence of infection compared with
      villages with untreated nets. The impact of use of treated bed nets on other
      arthropod pests lasted for at least 1.5 months. After 1.5 months, observations on
      arthropod pests were not continued. The use rate of treated nets varied from 49.8
      to 93.7% in three seasons and about 68.3% of treated bed nets and 60% of
      untreated nets were in good condition 1 year after distribution. Out of 489 users
      of treated net, five people complained of a burning sensation on the face (skin
      irritation) for 5 days following the distribution of treated nets. There were no
      other complaints of any discomfort in using the treated nets. The use of
      alphacypermethrin treated bed nets at 20 mg (ai)/m2 can be one of the options for
      reducing the vector abundance and incidence of malaria in this area.

PMID- 14636984
TI  - Bacteremia in adults admitted to the Department of Medicine of Bangui Community
      Hospital (Central African Republic).
AB  - To determine which pathogens are responsible for bloodstream infections in Bangui
      and to which antibiotics these pathogens are resistant, we conducted a
      prospective study of the bacteria isolated from the blood of febrile patients
      hospitalized in the department of medicine of the Bangui Community Hospital after
      the failure of antimalarial treatment. One hundred and thirty-one patients were
      included in this study. Bacteria were identified in 49 blood cultures (37.4%).
      Eleven different species were identified. Bacteremia was more frequent in HIV
      positive patients than in HIV-negative patients. Salmonella typhimurium,
      Mycobacterium tuberculosis and Streptococcus pneumoniae were the most frequently
      isolated pathogens. Eighty percent of enterobacteria were resistant to
      amoxicillin and 85% to trimethoprim-sulfamethoxazole. Ciprofloxacin and
      ceftriaxone were the most efficient antibiotics for the enterobacteria, but
      chloramphenicol and gentamicin were efficient in most cases. Some strains of S.
      pneumoniae displayed reduced susceptibility to penicillin G, but all strains were
      susceptible to erythromycin.

PMID- 14636985
TI  - Helminth antigens (Taenia solium, Taenia crassiceps, Toxocara canis, Schistosoma
      mansoni and Echinococcus granulosus) and cross-reactivities in human infections
      and immunized animals.
AB  - Helminth antigens were investigated in the search for accessible heterologous
      antigens capable to discriminate different helminthiases, by the enzyme linked
      immunosorbent assay (ELISA) and the immunoblot assay (IB). Antigens used were:
      Taenia solium cysticercus total saline (Tso); Taenia crassiceps cysticercus
      vesicular fluid (Tcra-VF); T. crassiceps cysticercus glycoproteins (Tcra-GP and
      Tcra-(18-14)-GP); Toxocara canis larva excretory-secretory (TES); Schistosoma
      mansoni adult total saline (Sm) and Echinococcus granulosus hydatid fluid (Eg).
      The assayed sera were from patients with: cysticercosis (n = 18); toxocariasis (n
      = 40); schistosomiasis (n = 19) and hydatidosis (n = 50) with proven clinical and
      laboratory diagnosis, and sera from rabbits immunized with Tso, Tcra-VF, TES and
      Eg. Cross-reactivity occurred mostly between infections caused by Taenia and
      Echinococcus or in immunized rabbits, by ELISA. Moreover, the cross-reactivity
      among helminthiases was found with the use of antigens belonging to
      phylogenetically related parasite species, Eg, Tso and Tcra-VF, by sharing same
      antigenic components. Lower cross-reactivities were obtained by IB technique,
      when only peptides were considered as antigens, and the use of T. crassiceps
      purified glycoproteins demonstrated high sensitivity and specificity in the
      diagnosis of human cysticercosis, similarly to that using homologous antigen
      (Tso) by the same technique.

PMID- 14636986
TI  - Cross-reactivity between Anisakis simplex sensitization and visceral larva
      migrans by Toxocara canis.
AB  - The aim of this work was to study cross-reactivity in the diagnosis of two
      related ascaridosis. Nineteen patients diagnosed with recidivous acute urticaria
      (RAU) caused by Anisakis simplex and 26 patients diagnosed with visceral larva
      migrans (VLM) caused by Toxocara canis were studied employing commercial
      diagnostic kits and "in house" assay kits. Cross-reactivity observed was greater
      when using "in house" assay kits, suggesting that T. canis excretory-secretory
      antigens were not only recognized by antibodies from patients with RAU but with
      greater intensity compared to the A. simplex excretory-secretory antigens.

PMID- 14636987
TI  - Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal
      pathology.
AB  - Tumor necrosis factor-alpha (TNF) is one member of a large family of inflammatory
      cytokines that share common signal pathways, including activation of the
      transcription factor nuclear factor kappa B (Nf-kappa B) and stimulation of the
      apoptotic pathway. Data derived from early work supported a role for TNF as a
      skeletal catabolic agent that stimulates osteoclastogenesis while simultaneously
      inhibiting osteoblast function. The finding that estrogen deficiency was
      associated with increased production of cytokines led to a barrage of studies and
      lively debate on the relative contributions of TNF and other cytokines on bone
      loss, on the potential cell sources of TNF in the bone microenvironment, and on
      the mechanism of TNF action. TNF has a central role in bone pathophysiology. TNF
      is necessary for stimulation of osteoclastogenesis along with the receptor
      activator of Nf-kappa B ligand (RANKL). TNF also stimulates osteoblasts in a
      manner that hinders their bone-formative action. TNF suppresses recruitment of
      osteoblasts from progenitor cells, inhibits the expression of matrix protein
      genes, and stimulates expression of genes that amplify osteoclastogenesis. TNF
      may also affect skeletal metabolism by inducing resistance to 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) by a mechanism that extends to other
      members of the steroid hormone nuclear receptor family. Thus, TNF assails bone at
      many levels. This review will focus on the cellular and molecular mechanisms of
      TNF action in the skeleton that result in increased bone resorption and impaired
      formation. TNF and its signal pathway remains an important target for the
      development of new therapies for bone loss from osteoporosis and inflammatory
      arthritis.

PMID- 14636988
TI  - Beginnings of feedback inhibition, allostery, and multi-protein complexes.

PMID- 14636989
TI  - Genomics of the human Y-chromosome. 1. Association with male infertility.
AB  - The human Y chromosome contains over 60 million nucleotides, but least number of
      genes compared to any other chromosome and acts as a genetic determinant of the
      male characteristic features. The male specific region, MSY, comprising 95% of
      the Y chromosome represents a mosaic of heterochromatic and three classes of
      euchromatic (X-transposed, X-degenerate and ampliconic) sequences. Thus far, 156
      transcription units, 78 protein-coding genes and 27 distinct proteins of the Y
      chromosome have been identified. The MSY euchromatic sequences show frequent gene
      conversion. Of the eight massive palindromes identified on the human Y
      chromosome, six harbor vital testis specific genes. The human male infertility
      has been attributed to mutations in the genes on Y chromosome and autosomes and
      failures of several physical and physiological attributes including paracrine
      controls. In addition, deletion of any one or all the three azoospermia (AZFa,
      AZFb or AZFc) factor(s) and some still unidentified regulatory elements located
      elsewhere in the genome result in infertility. Characterization of palindromic
      complexes on the long arm of Y chromosome encompassing AZFb and AZFc regions and
      identification of HERV15 class of endogenous retroviruses close to AZFa region
      have facilitated our understanding on the organization of azoospermia factors.
      Considerable overlap of the AZFb and AZFc regions encompassing a number of genes
      and transcripts has been shown to exist. However, barring details on AZF,
      information on the exact number of genes or the types of mutations prevalent in
      the infertile male is not available. Similarly, roles of sizable body of
      repetitive DNA present in close association with transcribing sequences on the Y
      chromosome are yet not clear. In a clinical setting with known cases of
      infertility, systematic search for loss or gain of these repeat elements would
      help understand their biological role(s). We present a brief overview on the
      genetic complexity of the human Y chromosome in the context of human male
      infertility.

PMID- 14636990
TI  - Apicoplast genome of the coccidian Eimeria tenella.
AB  - Unicellular apicomplexans possess an algal-originated plastid referred to as an
      apicoplast. Although apicomplexan parasites are comprised of highly diverse
      protists, the complete apicoplast genome sequences have only been determined from
      the hematozoan Plasmodium falciparum and cyst-forming coccidian Toxoplasma
      gondii. Here, we report the third complete sequence of apicoplast genome from the
      intestinal coccidian Eimeria tenella that may serve as a new drug target against
      coccidiosis in the livestock. The AT-rich E. tenella plastid genome is a 35-kb
      circular element. Its gene organization resembles more closely that of T. gondii
      than P. falciparum. Although the E. tenella plastid genome contains an almost
      identical set of genes to that found in P. falciparum and T. gondii, its encoded
      genes share low or moderate homologies with their counterparts in the other two
      apicomplexans. With the addition of this coccidian plastid genome sequence, we
      attempted to reexamine the apicoplast genome evolution and performed phylogenetic
      reconstructions using maximum likelihood and Bayesian inference (BI) methods
      based on a concatenated dataset of plastid-encoded rpoB, rpoC1 and rpoC2
      proteins. All resulting rpo protein trees placed apicoplast as a sister to
      Euglena within the green lineage. On the other hand, many recent studies based on
      the organization of plastid genes and some nuclear-encoded plastid proteins have
      supported a common red algal ancestry of apicomplexan and dinoflagellate
      plastids. If the apicoplast indeed originated from a red ancestor, the green
      relationship of apicomplexan genes would probably imply that the ancestral host
      that gave rise to the (red) apicoplast might have already contained some primary
      green plastid genes.

PMID- 14636991
TI  - A structural and functional study of plastid RNAs homologous to catalytic
      bacterial RNase P RNA.
AB  - Ribonuclease P (RNase P), the ubiquitous enzyme required for 5' maturation of
      transfer RNA, is a ribonucleoprotein containing an essential RNA subunit. This
      RNA (P RNA) is the catalytic component of RNase P in Bacteria and some Archaea. A
      putative P RNA is encoded in the chloroplast genome of three algae: Cyanophora
      paradoxa, Porphyra purpurea and Nephroselmis olivacea. In no case, the P RNAs
      from the plastids were active in vitro in conditions where bacterial and some
      archaeal P RNAs are functional. By using lead-ion-induced hydrolysis, we conclude
      that the catalytic deficiency is most likely due to the perturbation of the
      global structure of the plastid P RNAs compared to the bacterial counterpart. As
      a consequence, the plastid P RNAs are unable to bind to the precursor tRNA
      substrates. We discuss these results in the context of plastid and RNase P
      evolution.

PMID- 14636992
TI  - Genomic structure and transcriptional regulation of Che-1, a novel partner of Rb.
AB  - We recently identified and cloned a novel human gene, Che-1, whose product
      interacts with both RNA polymerase II and the retinoblastoma gene product (Rb).
      Furthermore, we found that Che-1 overexpression counteracts the growth inhibitory
      effects of Rb, regulating in such way both transcription and cell proliferation.
      In this paper, we describe the genomic organization of the mouse orthologous Che
      1 gene and its promoter region. The promoter is TATA less and presents several
      potential transcription factor-binding motifs. Importantly, we showed that Che-1
      expression is regulated by a negative feedback mechanism, in which this protein
      is present on its own promoter repressing transcription.

PMID- 14636993
TI  - Gene structure and embryonic expression of mouse COP9 signalosome subunit 8
      (Csn8).
AB  - Csn8 is the smallest subunit of the constitutively photomorphogenic 9 (COP9)
      signalosome (CSN), which consists of eight distinct components. CSN is homologous
      to the lid subcomplex of the 26S proteasome and is a regulator of the ubiquitin
      proteasome pathway. Murine Csn8 is an ortholog of Arabidopsis COP9, which was
      originally identified as a key regulator of photomorphogenic development. CSN is
      essential for the viability of plants and flies, but the role of this conserved
      protein complex in development of vertebrate animals remains obscure. We report
      the genomic structure of murine Csn8 gene and the expression pattern of Csn8
      during early embryo development. Mouse Csn8 protein contains 209 amino acid
      residues and is encoded by a single gene located on chromosome 1. Csn8 is
      expressed in embryonic stem (ES) cells and throughout early embryo development
      from zygote, preimplantation embryos, to post-implantation embryos.
      Immunostaining studies revealed that Csn8 is predominantly present in the inner
      cell mass (ICM) of E3.5 blastocyst and is widely expressed in E9.5-day embryos.

PMID- 14636994
TI  - Genome-wide analysis of redox-regulated genes in a dinoflagellate.
AB  - In this study, the effects of 1 mM sodium nitrite, a reactive nitrogen species
      (RNS) generator, and 0.5 mM paraquat, which produces reactive oxygen species
      (ROS), on gene expression in the marine dinoflagellate species Pyrocystis lunula
      were investigated using microarrays containing 3500 complementary DNAs (cDNAs). A
      total of 246 differentially expressed genes were identified under these
      treatments: 204 genes were specifically regulated in response to nitrite and 37
      genes specifically to paraquat. Only six genes showed a dependence on both
      nitrite and paraquat, indicating that the two agents act predominantly via
      distinct pathways. Although many of these redox-regulated genes encode proteins
      from a diverse range of functional categories, the majority of them (68%)
      represent novel sequences. Temporary abnormal spherical cells occurred in nitrite
      treated cultures, but not in those exposed to paraquat, suggesting that this
      response involves a specific pathway triggered by RNS. The genes involved include
      one that encodes a transcription factor unique to dinoflagellates (HPl), and
      genes encoding proteins similar to those regulating developmental processes in
      plants and animals such as NYD-SP5, shaggy and calcium-dependent kinases, the
      COP9 signalosome complex, ubiquitin-related proteases and a metacaspase.

PMID- 14636995
TI  - Transcription of human cathepsin L mRNA species hCATL B from a novel alternative
      promoter in the first intron of its gene.
AB  - Cathepsin L is a lysosomal cysteine protease over-expressed in malignancy. It is
      very potent in degrading collagen, elastin, laminin and other components of the
      basement membrane and therefore, has been implicated in tumor invasion and
      metastasis. Two mRNA species, hCATL A and hCATL B, which contain an identical
      open reading frame and different 5'UTRs, were demonstrated to be encoded by the
      same gene located on chromosome 9q21-22. We have previously cloned and
      characterized the promoter responsible for the transcription of hCATL A (hCATL A
      promoter). However, it was not clear whether hCATL B is a splice variant of hCATL
      A or transcribed from a different promoter. In the present study, we demonstrate
      for the first time that hCATL B is transcribed from an alternate promoter (hCATL
      B promoter) located in the first intron of hCATL. This TATA-less promoter
      initiates transcription from two cytosine nucleotides present 191 and 367 bases
      upstream to the translation start codon. Deletion analysis revealed that the core
      promoter region lies upstream to these transcription initiation sites. This
      region contains several putative transcription factor-binding sites like AP-1, AP
      4, GATA-1, Lmo2, NF-kappa B, MZF-1, NF-AT, etc. In U-87 MG cells, hCATL B
      promoter exhibits at least six times less activity than our previously
      characterized hCATL A promoter. However, this promoter is significantly more
      active in malignantly transformed cells as compared to its activity in
      untransformed cells. Thus, our results conclusively demonstrate that hCATL B mRNA
      is transcribed from an alternate promoter. Increased transcriptional activity
      from this promoter contributes to the elevated cathepsin L expression in
      transformed cells.

PMID- 14636996
TI  - Molecular cloning and characterization of AP-2 epsilon, a fifth member of the AP
      2 family.
AB  - The mammalian AP-2 family of transcription factors consists of four members, AP-2
      alpha, AP-2 beta, AP-2 gamma and AP-2 delta, which play an important role in
      regulating gene expression during development and differentiation of multiple
      organs and tissues. The defining feature of the AP-2 family is a highly conserved
      carboxy-terminal basic helix-turn-helix domain that is involved in dimerization
      and sequence-specific DNA-binding. In this report, we use bioinformatics to
      identify both the mouse and human AP-2 epsilon, a fifth member of the AP-2
      family. The predicted mouse and human AP-2 epsilon proteins consist of 442 amino
      acids and show a high level of sequence similarity with other AP-2 proteins in
      the DNA-binding and dimerization domain and weak similarity in the N-terminal
      activation domain. Northern blot analysis reveals that among the adult mouse
      tissues examined, AP-2 epsilon is highly expressed in skin tissue. The human AP-2
      epsilon gene maps to chromosome 1p42, consists of seven exons spanning 23 kb and
      exhibits a genomic structure similar to other AP-2 family members. Human AP-2
      epsilon mRNA is expressed in human skin and keratinocytes grown in culture.
      Finally, we show that recombinant AP-2 epsilon can bind to AP-2 binding sequences
      from keratin promoters in electrophoretic mobility shift assays. Our study
      establishes AP-2 epsilon as a novel member of the AP-2 family, and suggests that
      it may play an important role in skin biology.

PMID- 14636997
TI  - Distinct organization of the candidate tumor suppressor gene RFP2 in human and
      mouse: multiple mRNA isoforms in both species- and human-specific antisense
      transcript RFP2OS.
AB  - In the present study, we describe the human and mouse RFP2 gene structure,
      multiple RFP2 mRNA isoforms in the two species that have different 5' UTRs and a
      human-specific antisense transcript RFP2OS. Since the human RFP2 5' UTR is not
      conserved in mouse, these findings might indicate a different regulation of RFP2
      in the two species. The predicted human and mouse RFP2 proteins are shown to
      contain a tripartite RING finger-B-box-coiled-coil domain (RBCC), also known as a
      TRIM domain, and therefore belong to a subgroup of RING finger proteins that are
      often involved in developmental and tumorigenic processes. Because homozygous
      deletions of chromosomal region 13q14.3 are found in a number of malignancies,
      including chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), we
      suggest that RFP2 might be involved in tumor development. This study provides
      necessary information for evaluation of the role of RFP2 in malignant
      transformation and other biological processes.

PMID- 14636998
TI  - Construction of a genomic library of wild rice and Agrobacterium-mediated
      transformation of large insert DNA linked to BPH resistance locus.
AB  - Here we report the first genomic library of wild rice constructed on a plant
      transformation-competent binary vector (BIBAC2) and transformation of the large
      insert DNA into rice via Agrobacterium. We selected Oryza officinalis for genomic
      library construction. The library consists of 55,296 clones and stored in one
      hundred forty-four 384-well plates. Random sampling of 140 clones indicated an
      average insert size of 71 Kb at a range of 15-235 Kb and 4.8% empty vectors. Four
      wheat chloroplast probes and four maize mitochondrial probes were hybridized
      separately to the library, showing that contamination with organellar DNAs is
      very low (0.61% and 0.04%, respectively). The binary bacterial artificial
      chromosome (BIBAC) library provides 5.3 haploid genome equivalents, implying a
      99.5% probability of recovering any specific sequence of interest. A stability
      test indicated that the large DNA inserts were stable in this BIBAC vector both
      in host cells of Escherichia coli and Agrobacterium. Two restriction-fragment
      length polymorphism (RFLP) markers R288 and C820, which co-segregate with brown
      planthopper (BPH) resistance gene Qbp2, were used to screen the library, and
      identified seven and eight positive clones, respectively. The candidate clones of
      target gene isolated from the library are directly used to transform cultivated
      rice. After screening the Agrobacterium strains and helper plasmids, and using an
      improved procedure of transformation, a BIBAC clone with 120 Kb O. officinalis
      DNA insert was successfully transferred into the rice genome via Agrobacterium
      mediated transformation. The system developed here should serve as source for
      gene discovery, gene cloning and genome-related research in wild rice.

PMID- 14636999
TI  - Functional diversity of potato SNF1-related kinases tested in Saccharomyces
      cerevisiae.
AB  - Sucrose nonfermenting 1 catalytic subunit (SNF1)-type protein kinases are members
      of a metabolite-sensing protein kinase family distributed ubiquitously from yeast
      to plants and animals. In yeast cells, SNF1 acts in complex with the activator
      subunit SNF4 and a member of the SIP1/SIP2/GAL83 family responsible for substrate
      definition. The potato (Solanum tuberosum) genome possesses at least two SnRK1s,
      designated PKIN1 and StubSNF1. In this study, potato kinase 1 (PKIN1) and
      StubSNF1 were analysed in the yeast two-hybrid system and characterised by
      suppression of yeast mutations. It was shown that StubSNF1 interacted with the
      GAL83 ortholog of potato, StubGAL83, and complemented the Delta snf1 mutation.
      Moreover, it suppressed Delta snf4 and Delta sip1,Delta sip2,Delta gal83
      deficiencies. In contrast, PKIN1 was unable to interact with StubGAL83 and did
      not rescue the yeast mutants. These data suggest different functions for PKIN1
      and StubSNF1 in potato.

PMID- 14637000
TI  - Absorption spectra of reconstituted visual pigments of a nocturnal prosimian,
      Otolemur crassicaudatus.
AB  - Absorption spectra of visual pigments characterize animal vision. The association
      between absorption spectra and amino acid (aa) sequences of pigments has been
      well established for the middle- to-long-wave-sensitive (M/LWS) class of cone
      visual pigments of vertebrates, known as the "five-sites" rule where amino acid
      residues at the 180th, 197th, 277th, 285th, and 308th sites mostly determine the
      spectra. For primate M/LWS pigments, however, applicability of the rule is not
      clear because of the scarcity of absorbance data collected directly from purified
      pigments. In particular, no prosimian pigment has been examined in vitro. In this
      study, we reconstituted visual pigments of a nocturnal prosimian, the greater
      galago (Otolemur crassicaudatus), which has the M/LWS cone and the rod visual
      pigments in its retina. The five residues of the galago M/LWS pigment are Ala,
      His, Tyr, Ala, and Ala, respectively, and its peak absorption spectra
      (lambda(max)) was measured to be 539 nm, which is virtually identical to the
      expected value from the rule (538 nm), showing that the five-sites rule holds for
      this prosimian. The lambda(max) of the rod visual pigment was measured as 502 nm.
      Accurate estimate of lambda(max) values is essential in establishing the
      molecular basis of visual pigment evolution.

PMID- 14637001
TI  - Putative FLJ20436 gene characterisation in goat. Observed ubiquitous expression
      in goat and transgenic mice allowed to restrict the location of an hypothesised
      insulator element.
AB  - Eukaryotic genomes are organised into independent domains through the
      establishment of boundaries which allow to have distinct pattern of gene
      expression both during development and in differentiated cells. The previously
      reported site independent expression of the mammary-specific goat alpha
      lactalbumin gene in transgenic mice suggested the existence of cis-regulatory
      elements located upstream of this gene. The nearby presence of a second
      ubiquitously expressed gene (the cyclin T1 gene) allowed to define two chromatin
      domains putatively separated by a boundary insulator-like element. In this study,
      the characterisation of a third putative gene (FLJ20436) present between the
      alpha-lactalbumin and the cyclin T1 loci is reported. It was found to be a
      functional gene, ubiquitously expressed both in goat and transgenic mice. A
      complex pattern of alternative splicing events was observed in several analysed
      tissues leading to various mRNAs and putative FLJ20436 proteins, as suggested in
      human and mouse species. This allowed us to assign this gene to one of the two
      hypothesised chromatin domains, refining the location of the potential insulator
      element.

PMID- 14637002
TI  - Gene expression profiling of human satellite cells during muscular aging using
      cDNA arrays.
AB  - It is well established that biological aging is associated with functional
      deficits at the cellular, tissue, organ and system levels, but the molecular
      mechanisms that control lifespan and age-related phenotypes are still not well
      understood. In order to investigate the molecular mechanisms underlying myoblast
      aging, we have used quantitative hybridization of a cDNA array of 2016 clones
      from a human skeletal muscle 3'-end cDNA library to monitor gene expression
      patterns of myoblasts of individuals with different ages (5 days old, 52 years
      old and 79 years old) and at different stages of proliferation (early,
      presenescent and senescent). We have shown that expression profiles in satellite
      cells vary with donor age, with an up-regulation of genes involved in muscle
      structure, muscle differentiation and in metabolism in the newborn, and a down
      regulation of genes involved in protein renewal in adults. We have also observed
      that myoblasts isolated from subjects of different ages have typical expression
      profiles at the beginning of their proliferative lifespan. However, this
      phenomenon progressively disappears as the cells approach senescence. In
      addition, even though some of the modifications are similar to those observed in
      other cell types, we have observed that many changes in gene expression are
      characteristic of the myoblasts, confirming the hypothesis that the program of
      replicative senescence is specific for each cell type. Finally, we have
      identified four potential new markers of presenescence for human myoblasts, which
      could be useful in developing therapeutic strategies.

PMID- 14637003
TI  - Identification and expression of Neu4, a novel murine sialidase.
AB  - A partial murine gene homologous to known mammalian sialidases reported in the
      Celera database is shown to encode a novel neuraminidase, designated as murine
      neuraminidase 4 (Neu4). The complete gene contains four exons and an open reading
      frame of 501 amino acids. It shows significant homology to the previously cloned
      neuraminidases with characteristic conserved motifs ascribed to the neuraminidase
      active site. Of the other known murine sialidases, it is most similar to Neu3
      (42%). A cDNA encoding the entire coding sequence was isolated from mouse brain
      and expressed as a recombinant protein in COS-7 cells. Cell lysates contained
      significantly increased sialidase activity over mock transfected cells,
      demonstrating that Neu4 is a bona fide neuraminidase.

PMID- 14637004
TI  - Blocking the T4 lysis inhibition phenotype.
AB  - Nonlysogenic Escherichia coli K cells exhibit a delay in lysis when infected by
      T4rII phage termed lysis inhibition (LIN). E. coli K cells expressing lambda rexB
      from either a prophage defective for rexA, or a multicopy plasmid supported T4rII
      infection, but prevented the establishment of LIN. In addition, E. coli null
      mutations in either the periplasmic "tail-specific protease" tsp, or the 10Sa RNA
      ssrA, completely blocked the establishment of LIN following T4 infections. The
      expression of rexB in the absence of rexA resulted in several cellular
      phenotypes, including aberrant cell surface morphology, the partial to near
      complete suppression of mutations of lambda S and T4t holin genes, and lysis by
      cells aging on plates or growing with high rexB expression at elevated
      temperatures. These activities of RexB were impeded in the presence of RexA.

PMID- 14637005
TI  - MdAP, a novel protein in apple, is associated with the major allergen Mal d 1.
AB  - Mal d 1, an 18-kDa intracellular pathogenesis-related protein (PR-10), has been
      known since long as the major apple allergen in Middle and Northern Europe.
      However, its biological function, as that of many other PR-10 proteins, is still
      unknown. In order to identify proteins putatively interacting with Mal d 1, an
      expression library of Malus domestica was screened using the yeast-two-hybrid
      (Y2H) system. A novel protein binding to two isoforms of Mal d 1 being used as
      'bait' was isolated. The deduced amino acid sequence from the corresponding full
      length cDNA of the predicted Mal d 1-Associated-Protein (MdAP) do not display any
      homology to known proteins, but shares 45% identity with a 'hypothetical protein'
      in Arabidopsis thaliana. Southern analysis of the apple genome indicated that
      MdAP, comprising 190 amino acids, is encoded by a single gene. The expression
      pattern of the 1-kb MdAP transcript resembled the expression profile of the
      different Mal d 1 isoforms in various apple organs, however at a much lower
      level. Furthermore, a huge variation in transcription levels of Mal d 1 isoforms
      was observed in apple tissue. For both, Mal d 1 and MdAP highest amounts of mRNAs
      were measured in ripe fruits and significantly lower amounts in vegetative tissue
      by quantitative reverse transcription-polymerase chain reaction (RT-PCR).

PMID- 14637006
TI  - mRNA 5' region sequence incompleteness: a potential source of systematic errors
      in translation initiation codon assignment in human mRNAs.
AB  - The amino acid sequence of gene products is routinely deduced from the nucleotide
      sequence of the relative cloned cDNA, according to the rules for recognition of
      start codon (first-AUG rule, optimal sequence context) and the genetic code. From
      this prediction stem most subsequent types of product analysis, although all
      standard methods for cDNA cloning are affected by a potential inability to
      effectively clone the 5' region of mRNA. Revision by bioinformatics and cloning
      methods of 109 known genes located on human chromosome 21 (HC 21) shows that 60
      mRNAs lack any in-frame stop upstream of the first-AUG, and that in five cases
      (DSCR1, KIAA0184, KIAA0539, SON, and TFF3) the coding region at the 5' end was
      incompletely characterized in the original descriptions. We describe the
      respective consequences for genomic annotation, domain and ortholog
      identification, and functional experiments design. We have also analyzed the
      sequences of 13,124 human mRNAs (RefSeq databank), discovering that in 6448 cases
      (49%), an in-frame stop codon is present upstream of the initiation codon, while
      in the other 6676 mRNAs (51%), identification of additional bases at the mRNA 5'
      region could well reveal some new upstream in-frame AUG codons in the optimal
      context. Proportionally to the HC 21 data, about 550 known human genes might thus
      be affected by this 5' end mRNA artifact.

PMID- 14637007
TI  - A comparison of single- and multi-payer health insurance systems and options for
      reform.
AB  - A major choice confronting many countries is between single-payer and multi-payer
      health insurance systems. This paper compares single-payer models in the areas of
      revenue collection, risk pooling, purchasing, and social solidarity. Single-payer
      and multi-payer systems each have advantages which may meet countries' priorities
      for their health insurance system. Single-payer systems are usually financed more
      progressively, and rely on existing taxation systems; they effectively distribute
      risks throughout one large risk pool; and they offer governments a high degree of
      control over the total expenditure on health. Multi-payer systems sacrifice this
      control for a greater ability to meet the diverse preferences of beneficiaries.
      Several major reforms of single-payer insurance systems--expansion of the role of
      private insurance and transformation to a multi-payer system--are then described
      and illustrated using specific country examples. These reforms have been
      implemented with some success in several countries but face several important
      challenges.

PMID- 14637008
TI  - Analysis of primary health care utilisation in south-western Finland--a tool for
      management.
AB  - Long-term health care planning is presently not based on the needs of the
      population at the local level in Finland but rather, it is based on retroactive
      economic values and already realised budget in hospital and primary health care.
      The existing health care structure and its health care practices continue to
      guide the supply of services. While we have the most extensive databases on
      primary health care and hospital services, such tools are not used in the
      broadest possible sense in the present health care planning at the local level.
      Simple and informative indicators available to health care planners and decision
      makers from databases at the local level were used to appraise the use of health
      care services. Statistical profiles of health care clients were classified by age
      groups within the health authority area (population of 13,000) of Paimio-Sauvo in
      south-western Finland with the intent to explain utilisation of primary health
      care services, their coverage, and repeat visits as well as groups not using
      those services. Physicians recorded reasons for each patient visit with the ICD
      10 categories. In the case municipalities, primary health care services provided
      100% coverage to children of 0-6 years of age and more than 70% coverage to other
      groups. Most primary health care expenditures were assessed for people 65 years
      or older in 2000. As an example of a municipality, hospital and primary health
      care expenditures within Paimio varied from 24 to 30.4% of the total obligations
      for the last 10 years.

PMID- 14637009
TI  - Analysis of hospital charges for ischemic stroke in Fukuoka, Japan.
AB  - OBJECTIVES: Stroke is a heavy economic burden on individuals, society, and health
      services in Japan, where health expenditures are rising rapidly. The objective of
      the present study was to examine medical services and demographic factors
      associated with increased inpatient charges for ischemic stroke in Japan.
      SUBJECTS AND METHODS: The study subjects were 316 patients with a principal
      diagnosis of acute ischemic stroke who were discharged from the National Kyushu
      Medical Center Hospital from 1 July 1995 through 31 June 1999. Demographic,
      clinical, and administrative data were retrospectively collected from medical
      records and the hospital Clinical Financial Information System (CFIS). The
      influence of social and medical factors on total charges was analyzed using the
      stepwise multiple regression model. RESULTS: Among the total subjects, the mean
      (median) length of hospital stay (LOHS) was 33 (30) days (range, 2-155 days). The
      mean (median) hospital charge per patient was US dollars 9020 (dollars 7974) with
      a range of dollars 336-54,509. The distribution of charges was 42% for
      fundamental, 17% for injection therapies, 13% for radiological test, 11% for
      other laboratory examinations, 3% for drugs, and 3% for operations. Stepwise
      multiple regression analysis revealed that LOHS was the key determinant of the
      hospital charge (partial R2=0.5993, P=0.0001). Operations (P=0.0001) and
      angiography (P=0.03) were also independent but less contributory determinants of
      the hospital charge. CONCLUSIONS: LOHS was strongly, positively associated with
      inpatient charges for ischemic stroke in Japan. This implies that significant
      charge reductions are more likely to rely on shortening LOHS, which probably can
      be achieved by altering reimbursement policies.

PMID- 14637010
TI  - The economics of public health: financing drug abuse treatment services.
AB  - Drug abuse treatment financing exhibits a heterogeneous set of sources from
      federal, state, and local governments, as well as private sources from insurance,
      patient out-of-pocket, and charity. A public health model of drug abuse treatment
      is presented for a market that can be characterized by excess demand in many
      communities and an implied policy of rationing. According to best estimates, as
      many as 6.7 million individuals may need treatment, but only an estimated 1.5
      million individuals actually participated in treatment episodes. Since, as
      demonstrated empirically, drug abuse treatment has a robust and positive social
      net benefit to society, it is perplexing that treatment financing stops with a
      rationing outcome that inhibits social welfare. The justification for public
      financing is centered on the external costs of drug addiction, but subsidization
      is grounded in the reality that a large number of addicted individuals do not
      have sufficient resources to pay for treatment out-of-pocket, nor do they have
      private insurance coverage. Social welfare losses are generated by financial
      arrangements that are inconsistent with rational budgeting theory and as such
      would lead to non-optimal organization and management of the drug abuse treatment
      system.

PMID- 14637011
TI  - Politicians' and hospital managers' trade-offs in the choice of reimbursement
      scheme: a discrete choice experiment.
AB  - Trade-offs in the choice of hospital reimbursement schemes are widely discussed
      in the health economics literature but no one has previously, to this authors'
      knowledge, made an attempt at quantifying how purchasers and providers trade-off
      anticipated outcomes of reimbursement schemes. The purpose of this study is to
      elicit Danish county council politicians' and hospital managers' preferences for
      the anticipated incentives and consequences embedded in reimbursement schemes
      using the discrete choice method. Results indicate that politicians and hospital
      managers agree that increasing the number of patients treated is the most
      important objective for the choice of reimbursement scheme. The second most
      important objective to the politicians is to provide budget safety whereas
      inducing increased quality of treatment is third. Hospital managers rank
      inducement of increased quality of treatment as the second most important
      objective and have the county's budget safety as their third most important
      objective.

PMID- 14637012
TI  - Measuring geographic inequities in the Portuguese health care system: an
      estimation of hospital care needs.
AB  - Portugal created a NHS to achieve greater equity of access to health care.
      Successive governments continued to assert the importance of equity in the face
      of evidence of inequities in supply of hospital resources, but lacked methods to
      provide sound information on the degree of inequities in Portugal and hence how
      to achieve greater equity. Capitation formulae have been increasingly used in
      other countries with a NHS to measure geographical inequities and allocate
      resources to reduce them. The main objective of this paper was to develop a
      capitation formula to measure need for hospital care for the Portuguese system by
      transferring this technology from methods used in other countries, and, in
      particular, in England. We find, however, problems with the common use of
      standardised mortality ratios (SMRs) as a measure of need and found age-specific
      mortality ratios to offer more soundly-based estimates. We also raise questions
      on the use of empirical estimates of utilisation of health care by age and sex as
      they appear to reflect inadequacies of health care in Portugal. We also believe
      it is important to improve knowledge of health insurance and care outside the
      NHS. Our results show that there are considerable inequities on the distribution
      of hospital resources in Portugal.

PMID- 14637013
TI  - Priority setting in a hospital drug formulary: a qualitative case study and
      evaluation.
AB  - Dramatically rising costs for new drugs are posing major challenges for hospital
      budgets. In response to these pressures, hospitals must set priorities for which
      drugs they will list on their formularies. While there have been studies relevant
      to decision making in hospitals regarding drugs, none have described how priority
      setting for drugs in hospitals is done and evaluated it against a framework of
      how it should be done. In this paper we describe the process of priority setting
      for new drugs in a hospital formulary and evaluate it using a leading conceptual
      framework for healthcare priority setting--Daniels and Sabin's 'accountability
      for reasonableness'. The findings from this study provide an evidence base for
      developing strategies to improve this hospital's priority setting regarding its
      drug formulary. The process we utilized here, describing using case study methods
      and evaluating using 'accountability for reasonableness', is a generalizable
      process for improving the fairness of priority setting in hospital drug
      formularies.

PMID- 14637014
TI  - Lipid rafts in epithelial brush borders: atypical membrane microdomains with
      specialized functions.
AB  - Epithelial cells that fulfil high-throughput digestive/absorptive functions, such
      as small intestinal enterocytes and kidney proximal tubule cells, are endowed
      with a dense apical brush border. It has long been recognized that the
      microvillar surface of the brush border is organized in cholesterol/sphingolipid
      enriched membrane microdomains commonly known as lipid rafts. More recent studies
      indicate that microvillar rafts, in particular those of enterocytes, have some
      unusual properties in comparison with rafts present on the surface of other cell
      types. Thus, microvillar rafts are stable rather than transient/dynamic, and
      their core components include glycolipids and the divalent lectin galectin-4,
      which together can be isolated as "superrafts", i.e., membrane microdomains
      resisting solubilization with Triton X-100 at physiological temperature. These
      glycolipid/lectin-based rafts serve as platforms for recruitment of GPI-linked
      and transmembrane digestive enzymes, most likely as an economizing effort to
      secure and prolong their digestive capability at the microvillar surface.
      However, in addition to microvilli, the brush border surface also consists of
      membrane invaginations between adjacent microvilli, which are the only part of
      the apical surface sterically accessible for membrane fusion/budding events. Many
      of these invaginations appear as pleiomorphic, deep apical tubules that extend up
      to 0.5-1 microm into the underlying terminal web region. Their sensitivity to
      methyl-beta-cyclodextrin suggests them to contain cholesterol-dependent lipid
      rafts of a different type from the glycolipid-based rafts at the microvillar
      surface. The brush border is thus an example of a complex membrane system that
      harbours at least two different types of lipid raft microdomains, each suited to
      fulfil specialized functions. This conclusion is in line with an emerging, more
      varied view of lipid rafts being pluripotent microdomains capable of adapting in
      size, shape, and content to specific cellular functions.

PMID- 14637015
TI  - Preparation and electrochemical behavior of gramicidin-bipolar lipid monolayer
      membranes supported on gold electrodes.
AB  - Gramicidin-containing synthetic bolalipid membranes comprised of 2,2'-di-O-decyl
      3,3'-O-1,20-eicosanyl-bis-rac-glycero-1,1'-diphosphocholine (C20BAS) have been
      synthesized and supported on gold electrodes. Supported membranes were prepared
      by first depositing a partial bolalipid layer on the electrode using a thioctic
      acid-modified bolalipid (1'-O-omega-thioctamidetetraethylene glycol-2,2'-di-O
      decyl-3,3'-di-O-1,20-eicosanyl-bis-rac-glycero-1-phosphate, SSC20BAS) as an
      anchoring group, followed by a vesicle fusion step using either pure C20BAS or
      gramicidin-containing C20BAS (C20BAS-GA) vesicles. The latter configuration was
      designed to immobilize single, continuously-on channels of gramicidin in the
      C20BAS membrane. Vesicle deposition to form supported bolalipid monolayer
      membranes was monitored by impedance spectroscopy and cyclic voltammetry.
      Impedances were observed to increase with vesicle deposition time. Pretreatment
      of the impedance electrode with SSC20BAS accelerated the supported monolayer
      membrane deposition rate. Impedances decreased in a gramicidin concentration
      dependent manner when gramicidin was incorporated into the C20BAS membrane. These
      supported bolalipid membranes are also surprisingly inert to organic solvent
      exposure (CH(3)CH(2)OH;CH(2)Cl(2)), suggesting that they may serve as robust host
      matrices for integral membrane protein-based sensors.

PMID- 14637016
TI  - The hemolytic activity of six arachnid cationic peptides is affected by the
      phosphatidylcholine-to-sphingomyelin ratio in lipid bilayers.
AB  - The hemolytic activity of six cationic amphipathic peptides (Oxki1, Oxki2, Pin1,
      Pin2, IsCT1 and IsCT2) from arachnids strongly depends on the source of red blood
      cells. The hemolytic activity of the amphipathic peptides was correlated to the
      phosphocholine-to-sphingomyelin ratio (PC/SM) content, the potency order of which
      on mammal erythrocytes ranked as follows Guinea pig>pig>sheep. The spider
      peptides, Oxki1 and Oxki2, prefer small unilamellar vesicles (SUV) composed of
      PC, but they could not disrupt SUVs made of SM only. Moreover, the membrane
      disrupting activity of the scorpion peptide Pin1 was affected by increasing
      concentrations of SM. Only the scorpion hemolytic peptide Pin2 was able to
      disrupt SUVs composed merely of SM at high concentrations. Finally, the short
      scorpion peptides IsCT1 and IsCT2 seem to tolerate high concentrations of SM in
      the presence of PC for disruption of SUVs; however, the disrupting activities of
      IsCT1 and IsCT2 are much lower than that of the other four hemolytic peptides.
      The hemolytic activity caused by all six cationic peptides in mammalian
      erythrocytes was positively correlated to increases in temperature and increases
      in the concentration of benzyl alcohol, a membrane fluidizing agent. It was
      concluded that the hemolytic activity of the cationic peptides strongly depends
      on the PC/SM content of mammalian erythrocytes, in which cell membranes with a
      low PC/SM ratio (i.e., of low fluidity) were less disturbed than membranes with a
      high PC/SM ratio (i.e., of high fluidity).

PMID- 14637017
TI  - Topology of factor VIII bound to phosphatidylserine-containing model membranes.
AB  - Factor VIII (FVIII), a plasma glycoprotein, is an essential cofactor in the blood
      coagulation cascade. It is a multidomain protein, known to bind to
      phosphatidylserine (PS)-containing membranes. Based on X-ray and electron
      crystallography data, binding of FVIII to PS-containing membranes has been
      proposed to occur only via the C2 domain. Based on these models, the molecular
      topology of membrane-bound FVIII can be envisioned as one in which only a small
      fraction of the protein interacts with the membrane, whereas the majority of the
      molecule is exposed to an aqueous milieu. We have investigated the topology of
      the membrane-bound FVIII using biophysical and biochemical techniques. Circular
      dichroism (CD) and fluorescence studies indicate no significant changes in the
      secondary and tertiary structure of FVIII associated with the membranes.
      Acrylamide quenching studies show that the protein is predominantly present on
      the surface of the membrane, exposed to the aqueous milieu. The light scattering
      and electron microscopy studies indicate the absence of vesicle aggregation and
      fusion. Binding studies with antibodies directed against specific epitopes in the
      A1, A2 and C2 domains suggest that FVIII binds to the membrane primarily via C2
      domain including the specific phospholipid binding epitope (2303-2332) and may
      involve subtle conformational changes in this epitope region.

PMID- 14637018
TI  - Preferential orientation of an immunoglobulin in a glycolipid monolayer
      controlled by the disintegration kinetics of proteo-lipidic vesicles spread at an
      air-buffer interface.
AB  - The insertion of immunoglobulin (IgG) in a glycolipid monolayer was achieved by
      using the ability of new proteo-glycolipid vesicles to disintegrate into a mixed
      IgG-glycolipid interfacial film after spreading at an air-buffer interface. The
      interfacial disintegration kinetics was shown to be directly dependent on the
      initial vesicle surface density and on the buffer ionic strength. The presence of
      the immunoglobulin in the glycolipid film was displayed by an increase of the
      lateral compressibility (Cs) during monolayer compression. Cs magnitude
      modifications, due to the antibody effect on the monolayer packing, decreases as
      the spread vesicle density increases. At interfacial saturation, the lateral
      compressibility profile becomes similar to that of a control monolayer without
      antibody. However, the careful analysis of the mixed monolayer after transfer by
      Langmuir-Blodgett technique (ATR-FTIR characterisation, enzyme immunoassociation)
      clearly demonstrated that the antibody was still present in such conditions and
      was not completely squeezed out from the interface as compressibility changes
      could have meant. At nonsaturating vesicle surface density, IgG molecules
      initially lying in the lipid matrix with the Y-shape plane parallel to the
      interface move to a standing-up position during the compression, leading to
      lateral compressibility modifications. For a saturating vesicle surface density,
      the glycolipid molecules force the IgG molecules to directly adopt a more
      vertical position in the interfacial film and, consequently, no lateral
      compressibility modification was recorded during the compression.

PMID- 14637019
TI  - Intracellular dynamics of the gene delivery vehicle polyethylenimine during
      transfection: investigation by two-photon fluorescence correlation spectroscopy.
AB  - Though polyethylenimine (PEI) is one of the most efficient nonviral vectors, one
      concern is the significant cytotoxicity of free PEI that represents about 80% of
      the PEI molecules in PEI/DNA mixtures used for transfection. In this respect, the
      aim of this work was to further investigate the intracellular fate of PEI during
      transfection of L929 fibroblasts. To this end, we analyzed by fluorescence
      correlation spectroscopy (FCS) using two-photon excitation the intracellular
      concentration and diffusion properties of labeled PEI and PEI/DNA complexes in
      various compartments of L929 cells. High initial fluorescence intensity, rapid
      photobleaching and the absence of measurable autocorrelation curves in most
      selected locations in cytoplasm suggest that PEI/DNA complexes and PEI accumulate
      (up to 30 times the concentration in the extracellular medium) in late endosomes
      bound to the inner membrane face. This feature, together with membrane
      destabilizing properties of PEI, may explain the release of PEI into cytoplasm
      and subsequent diffusion into the nucleus. In the nucleus, the concentration of
      PEI was found to be about 2.5- to 3.5-fold higher than the one in the incubation
      medium. Moreover, autocorrelation curves obtained in the nuclear compartment can
      be analyzed with either a two-component model (with the major fraction undergoing
      free Brownian diffusion) or an anomalous diffusion model. Both the endosomal
      disruption and the large intranuclear PEI concentration may contribute to PEI
      cytotoxicity.

PMID- 14637020
TI  - The fusion peptide of simian immunodeficiency virus and the phase behaviour of N
      methylated dioleoylphosphatidylethanolamine.
AB  - Temperature-scan X-ray scattering was used to study the effect of the fusion
      peptide of simian immunodeficiency virus (SIV) on the lipid polymorphism of N
      methylated dioleoylphosphatidylethanolamine (DOPE-Me), in the presence and
      absence of one or both of the fusion inhibitors carbobenzoxy-D-phenylalanine-L
      phenylalanine-glycine and 1-lauroyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC).
      Using X-ray diffraction at stations 2.1 and 8.2 of the Synchrotron Radiation
      Source at Daresbury Laboratory, UK, the structure of multilamellar vesicles
      (MLVs) was probed as the temperature was raised from 20 to 90 degrees C. The
      results are compared to those of similar studies, reported earlier, that used the
      fusion peptide of feline leukaemia virus (FeLV) which, at 28 amino acid residues
      in length, is considerably longer than the SIV peptide (12 amino acid residues).
      We interpret the results within the framework of current understanding of
      membrane fusion, and demonstrate how observed lipid polymorphism might describe
      the fusion process.

PMID- 14637021
TI  - Conformation and self-assembly of a nystatin nitrobenzoxadiazole derivative in
      lipid membranes.
AB  - Nystatin is a polyene (tetraene) macrolide antibiotic presenting antifungal
      activity that acts at the cellular membrane level. In the present study, we
      report the interaction of this antibiotic labelled at its amine group with 7
      nitrobenz-2-oxa-1,3-diazole (NBD-Nys) with sterol-free and ergosterol- and
      cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      large unilamellar vesicles (LUV). The mean tetraene to NBD separating distance
      determined from fluorescence energy transfer measurements increased from 18 to
      25.6 A upon antibiotic binding to the lipid vesicles, indicating that the
      monomeric labelled antibiotic adopts a more extended conformation in its lipid
      bound state than in aqueous solution. The oligomeric state of membrane-bound NBD
      Nys was also studied by resonance energy homotransfer between the NBD
      fluorophores. The decrease measured in its steady state fluorescence anisotropy
      upon increasing the surface concentration of the NBD-Nys is shown to be
      consistent with a random distribution of molecules on the surface of the
      liposomes. This data contradicts the sharp increase measured for nystatin mean
      fluorescence lifetime in the presence of 10 mol% ergosterol-containing POPC LUV
      within the same antibiotic concentration range and which is known to report
      nystatin oligomerization in the lipid vesicles. Therefore, we conclude that the
      amine group of nystatin is an essential requisite for the supramolecular
      organization/pore formation of this antibiotic.

PMID- 14637022
TI  - Interaction of RANTES with syndecan-1 and syndecan-4 expressed by human primary
      macrophages.
AB  - Interaction of RANTES with its membrane ligands or receptors transduces multiple
      intracellular signals. Whether RANTES uses proteoglycans (PGs) belonging to the
      syndecan family to attach to primary cells expressing RANTES G-protein-coupled
      receptors (GPCRs) was investigated. We demonstrate that RANTES specifically binds
      to high and low affinity binding sites on human monocyte-derived macrophages
      (MDM). We show by co-immunoprecipitation experiments that RANTES is associated on
      these cells with syndecan-1 and syndecan-4, but neither with syndecan-2 nor with
      betaglycan, in addition to CD44 and its GPCRs, CCR5 and CCR1. Glycosaminidases
      pre-treatment of the monocyte derived-macrophages strongly decreases the binding
      of RANTES to syndecan-1 and syndecan-4 and also to CCR5, and abolishes RANTES
      binding to CD44. This suggests that glycosaminoglycans (GAGs) are involved in
      RANTES binding to the PGs and that such bindings facilitate the subsequent
      interaction of RANTES with CCR5, on the MDM, characterized by low membrane
      expression of CCR5. The role of these interactions in the pathophysiology of
      RANTES deserves further study.

PMID- 14637023
TI  - Aggregation properties of mycolic acid molecules in monolayer films: a
      comparative study of compounds from various acid-fast bacterial species.
AB  - Three kinds of mycolic acids (MAs) (alpha-, keto and methoxy-MAs) extracted from
      several species of mycobacteria were used to prepare monolayer films on water,
      and the surface pressure-area (pi-A) isotherms of the monolayers have been
      compared, so that the monolayer characteristics of the MAs as in cell walls would
      be revealed, since the monolayer molecular aggregation is related to drug
      permeability via the molecular packing. It was expected that the limiting
      molecular areas of the isotherms would be changed only a little, which reflects
      the minor difference in chemical structure and conformation of the mycobacteria.
      Nevertheless, the results are largely different from the expectation, and two
      greatly different patterns of the limiting molecular area have been observed. In
      a new model for elucidation of the results, two parts in an MA molecule are
      separately considered, and both contributions to the molecular unfolding by the
      monolayer compression have been suggested. This model is found to be useful to
      totally understand the isotherm behaviors of MAs. The relationship between
      monolayer properties and chemical structures for MAs has been summarized for the
      first time.

PMID- 14637024
TI  - The F-G loop region of cytochrome P450scc (CYP11A1) interacts with the
      phospholipid membrane.
AB  - Cytochrome P450scc (CYP11A1) is a protein attached to the inner surface of the
      inner mitochondrial membrane that uses cholesterol from the membrane phase as its
      substrate for the first step in steroid hormone synthesis. We investigated the
      mechanism by which CYP11A1 interacts with the membrane. Hydrophobicity profiles
      of CYP11A1 and two other mitochondrial cytochromes P450, plus a model structure
      of CYP11A1 using CYP2C5 as template, suggest that CYP11A1 has a monotopic
      association with the membrane which may involve the A' helix and the F-G loop.
      Deletion of the A' helix reduced the proportion of expressed CYP11A1 associated
      with the bacterial membrane fraction, indicating a role for the A' helix in
      membrane binding. However, introduction of a cysteine residue in this helix at
      position 24 (L24C) and subsequent labelling with the fluorescent probe N'-(7
      nitrobenz-2-oxal,3-diazol-4-yl)ethylenediamine (NBD) failed to show a membrane
      localisation. Cysteine mutagenesis and fluorescent labelling of other residues
      appearing on the distal surface of the CYP11A1 model revealed that V212C and
      L219C have enhanced fluorescence and a blue shift following association of the
      mutant CYP11A1 with phospholipid vesicles. This indicates that these residues,
      which are located in the F-G loop, become localised to a more hydrophobic
      environment following membrane binding. Analysis of the quenching of tryptophan
      residues in CYP11A1 by acrylamide indicates that at least one and probably two
      tryptophans are involved in membrane binding. We conclude that CYP11A1 has a
      monotopic association with the membrane that is mediated, at least in part, by
      the F-G loop region.

PMID- 14637025
TI  - Membrane permeabilizing activity of amphotericin B is affected by chain length of
      phosphatidylcholine added as minor constituent.
AB  - The effect of acyl-chain length of phospholipid on the membrane permeabilizing
      activity of amphotericin B (AmB) was examined using egg phosphatidylcholine
      (eggPC) liposomes containing 5% or 20% phosphatidylcholine with various lengths
      of fatty acyl chains from C(10) to C(18); 1,2-dicapryloyl-sn-glycero-3
      phosphocholine (DCPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2
      dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The
      membrane activity of AmB was evaluated by two methods; the drug was added to a
      liposome suspension (added-via-aqua), or mixed with lipids prior to liposome
      preparation (mixed-with-lipid). In both cases, K(+) influx by AmB was measured as
      pH change inside liposomes by 31P-NMR. The C(10) and C(12) acyl phospholipids
      markedly enhanced the activity of AmB, the C(14) and C(16) lipids virtually
      showed no effect, and the C(18) lipid was inhibitory to the AmB's action. Clear
      distinction between the C(12) and C(14) lipids, which differ only in acyl chains
      by two carbons, implies that molecular interaction between phospholipid and AmB
      is partly due to the matching of their hydrophobic length.

PMID- 14637026
TI  - Epidemiology of Sarcocystis neurona infections in domestic cats (Felis
      domesticus) and its association with equine protozoal myeloencephalitis (EPM)
      case farms and feral cats from a mobile spay and neuter clinic.
AB  - Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease in the
      horse most commonly caused by Sarcocystis neurona. The domestic cat (Felis
      domesticus) is an intermediate host for S. neurona. In the present study, nine
      farms, known to have prior clinically diagnosed cases of EPM and a resident cat
      population were identified and sampled accordingly. In addition to the farm cats
      sampled, samples were also collected from a mobile spay and neuter clinic.
      Overall, serum samples were collected in 2001 from 310 cats, with samples
      including barn, feral and inside/outside cats. Of these 310 samples, 35 were from
      nine horse farms. Horse serum samples were also collected and traps were set for
      opossums at each of the farms. The S. neurona direct agglutination test (SAT) was
      used for both the horse and cat serum samples (1:25 dilution). Fourteen of 35
      (40%) cats sampled from horse farms had circulating S. neurona agglutinating
      antibodies. Twenty-seven of the 275 (10%) cats from the spay/neuter clinic also
      had detectable S. neurona antibodies. Overall, 115 of 123 (93%) horses tested
      positive for anti-S. neurona antibodies, with each farm having greater than a 75%
      exposure rate among sampled horses. Twenty-one opossums were trapped on seven of
      the nine farms. Eleven opossums had Sarcocystis sp. sporocysts, six of them were
      identified as S. neurona sporocysts based on bioassays in gamma-interferon gene
      knockout mice with each opossum representing a different farm. Demonstration of
      S. neurona agglutinating antibodies in domestic and feral cats corroborates
      previous research demonstrating feral cats to be naturally infected, and also
      suggests that cats can be frequently infected with S. neurona and serve as one of
      several natural intermediate hosts for S. neurona.

PMID- 14637027
TI  - Gastrointestinal parasites of domestic cats in Perth, Western Australia.
AB  - A study was conducted to determine the prevalence of gastrointestinal parasites
      in a sample of domestic cats in Perth and the knowledge of their owners about the
      control and potential for zoonotic transmission of these parasites. Faecal
      samples (418), collected from cats originating from five sources, were examined
      by microscopy and questionnaires administered to cat owners. Forty randomly
      selected samples were also screened using PCR in order to detect cysts of Giardia
      and oocysts of Cryptosporidium that may have been present in a faecal sample at
      very low levels. The overall prevalence of gastrointestinal parasites in domestic
      cats by microscopy was 8.6%. Pet shop kittens had the highest parasite prevalence
      (34.3%), followed by cats and kittens from breeding establishments (15.8%),
      refuge cats and kittens (8.3%), privately owned cats (2.3%), and boarding cats
      and kittens (1.6%). Surprisingly, 80% of the 40 cats tested by PCR were positive
      for Giardia duodenalis and 10% for Cryptosporidium. None of these cats were
      positive on microscopy. After adjusting for other factors with multiple logistic
      regression, kittens less than 6 months of age, and cats living in households with
      more than one cat or with a dog were significantly more likely to be parasitised.
      In the logistic regression model, the presence of parasitism was also
      significantly influenced by the number of anthelmintic doses administered in the
      12 month period prior to the study. The majority (64.5%) of cat owners were aware
      that feline parasites could be transmitted to humans, however less than half
      (42.8%) were aware of the modes of transmission to humans.

PMID- 14637028
TI  - Presence and persistence of intestinal parasites in canine fecal material
      collected from the environment in the Province of Chubut, Argentine Patagonia.
AB  - We investigated the presence of intestinal parasites in canine feces collected
      from public squares in Comodoro Rivadavia, Chubut, Argentina (45 degrees S, 68
      degrees W) and determined the persistence of Echinococcus granulosus eggs in
      those droppings under natural environmental conditions in that region. In the
      first experiment, we analyzed 163 fecal samples collected from urban squares
      during 8 months time and found parasitic elements in 46.6%. The presence of
      parasites was independent of the condition of the feces (fresh or dried; P>0.05).
      Parasites potentially pathogenic in man were present, such as Toxocara species
      (spp.), Taenia spp./Echinococcus spp., Uncinarias spp., and Entamoeba spp. In the
      second experiment, we analyzed two canine fecal samples contaminated with E.
      granulosus eggs, deposited for 41 months within the natural environment. These
      parasitic elements persisted during the entire study as attested by light
      microscopy and the ELISA coproantigen test. We propose the study of the presence
      of intestinal parasites in canine feces within the environment as a general
      strategy for identifying and monitoring areas of risk for canine-related zoonoses
      since we were able to demonstrate the persistence of E. granulosus eggs in
      deposited canine feces for over 3 years within the area studied.

PMID- 14637029
TI  - Acquired resistance of horses to Amblyomma cajennense (Fabricius, 1787) ticks.
AB  - Acquired immunity of horses to larvae, nymphs and adults of the Amblyomma
      cajennense tick was evaluated through three consecutive experimental infestations
      of tick-bite naive hosts. Data from these infestations were compared to those
      from field-sensitized horses and donkeys. It was observed that tick-bite naive
      horses developed a low level of resistance after two infestations as shown by a
      significant decrease in larval yield and a tendency for lower engorged weight of
      nymphs during third infestation. Ticks fed on field-sensitized horses had a
      similar biological performance to that observed on the third infestation of tick
      bite naive horses but the mean engorged nymph weight was significantly lower than
      that of the first infestation from tick-bite naive horses. Donkeys presented the
      strongest resistance with significantly lower engorged weights of all instars and
      of the egg mass compared to the first infestation of tick-bite naive horses.
      Donkeys also displayed a significantly higher resistance than field-sensitized
      horses as demonstrated by significantly lower egg mass weights. Overall these
      results indicate that donkeys but not horses maintain a strong resistance to A.
      cajennense ticks. The importance of these findings in relation to vectoring of
      tick-borne diseases is discussed.

PMID- 14637030
TI  - Ehrlichiosis in anemic, thrombocytopenic, or tick-infested dogs from a hospital
      population in South Brazil.
AB  - Ehrlichia canis has a worldwide distribution, but clinical manifestations may
      vary geographically. We selected 129 dogs to determine prevalence of ehrlichiosis
      in dogs with anemia, thrombocytopenia, or ticks presented to a Veterinary
      Teaching Hospital in South Brazil. Of the 129 dogs, 68 carried the brown dog tick
      (Rhipicephalus sanguineus), 61 had thrombocytopenia (platelet count
      <150,000/microl), and 19 had anemia (PCV < 22%). Twenty dogs fulfilled more than
      one inclusion criteria. Ehrlichiosis was diagnosed by positive amplification of
      ehrlichial DNA by PCR using primers ECC and ECB that amplify a sequence of the
      16S rRNA gene. Presence of E. canis was confirmed by cleavage of the amplified
      DNA using endonucleases HaeIII and AvaI. Fourteen of 68 (21%) dogs with ticks had
      ehrlichiosis, whereas 12 of 61 (20%) dogs presented with thrombocytopenia and 4
      of 19 (21%) anemic dogs had ehrlichiosis. Similar results were obtained in dogs
      with thrombocytopenia and anemia (one of eight positive) and in dogs with
      thrombocytopenia and ticks (two of seven positive). All four dogs with anemia and
      ticks, and the dog that fulfilled all inclusion criteria yield no amplification
      of ehrlichial DNA by PCR. Based on our results, one in each five dogs infested by
      the brown dog tick, with anemia or thrombocytopenia had ehrlichosis. Contrary to
      widespread believe, ehrlichiosis was not the main cause for thrombocytopenia in
      our region.

PMID- 14637031
TI  - Effect of horn fly and internal parasite control on growth of beef heifers.
AB  - The effects of horn fly and gastrointestinal nematode control on body weight gain
      of yearling Angus-Brangus cross heifers were evaluated in three separate studies
      during the years 1999, 2000 and 2002. In each year, the studies started in late
      May and lasted for 150, 148 and 123 days, respectively. In all three studies, the
      tag treatment (10% lambdacyhalothrin+13% piperonyl butoxide impregnated ear tags)
      provided excellent horn fly control. In the three studies, the average weekly
      horn fly counts for tagged heifers were 1, 3, and 0 flies per side while the
      average on untreated heifers was 52, 163 and 90 flies per side. In studies 1 and
      2, there was no difference (P>0.1) in weight gain between tagged and untreated
      heifers, but in study 3, tagged heifers gained 50% more weight (P<0.001) than the
      untreated heifers. For gastrointestinal nematode control, ivermectin (IVM) was
      administered on Day 0 in studies 1 and 3 using a sustained release bolus and on
      Day 0 and subsequent 56-day intervals in study 2 using either the injectable or
      pour-on formulation. Heifers treated with IVM in studies 1 and 3 had
      significantly lower (P<0.05) GI nematode fecal egg counts compared to control
      heifers. In study 2, IVM treated heifers also had significantly lower GI nematode
      fecal egg counts compared to control heifers, except for Day 90 when no
      differences in fecal egg counts were observed between IVM pour-on treated and
      control heifers. Weight gain of heifers that received IVM was significantly
      greater (P<0.005) than untreated heifers in each of the three studies. IVM
      treated heifers gained 45, 61 and 184% more weight than the untreated heifers
      during the three studies. There was no interaction (P>0.1) between the main
      treatment effects of fly control and gastrointestinal nematode control.

PMID- 14637032
TI  - Detection of Neospora caninum in semen of bulls.
AB  - In cattle, transplacental infection is the main route of Neospora caninum
      transmission, but postnatal transmission by the oral uptake of sporozoite
      containing oocysts shed by dogs may also be possible. Other routes of horizontal
      transmission, such as the venereal route, have not been investigated. In this
      study, we evaluated the presence of N. caninum DNA by a nested-PCR in fresh non
      extended semen and frozen extended semen straws of five Holstein-Friesian bulls
      with naturally-acquired neosporosis. The infection status was assessed by an
      immunofluorescent antibody test (IFAT) and confirmed by immunoblotting (IB).
      Because of inhibitory components of semen, a protocol was developed to purify N.
      caninum DNA from bovine semen. Sporadically, N. caninum DNA was detected in non
      extended fresh semen samples and frozen extended semen straws of the five
      seropositive bulls. In all positive samples, specific DNA was consistently found
      in the cell fraction of semen and not in seminal plasma. The parasite mean load
      in positive fresh semen samples determined by a real-time PCR was low oscillating
      between 1 and 2.8 parasites/ml of semen (maximum parasite load detected in one
      sample was 7.5 parasites/ml of semen). In parallel, another three similar but
      uninfected bulls acted as controls and no N. caninum DNA was amplified in any of
      their fresh and straw semen samples assayed. Whether venereal transmission plays
      a role in the spread of bovine neosporosis needs to be determined.

PMID- 14637033
TI  - Variation in population density of horn flies (Haematobia irritans irritans) (L.)
      (Diptera: Muscidae) in Nellore cattle (Bos indicus).
AB  - The population density of horn flies was evaluated in the year 1998 in the
      municipality of Aracatuba, Sao Paulo Brazil, in relation to temperature and
      rainfall conditions. Two lots of 30 Nellore steers (Bos indicus) were used which
      had no insecticidal treatment and were naturally infested with horn flies. The
      infestations were assessed by two counting methods, i.e., the traditional
      estimate method and the filming method. The highest fly frequencies were recorded
      in spring, summer, autumn and the lowest frequencies were recorded in winter. The
      increase in fly number was positively correlated (P<0.05) with rainfall.

PMID- 14637034
TI  - In vivo cytokine response to experimental feline infectious peritonitis virus
      infection.
AB  - Feline infectious peritonitis virus (FIPV) is a coronavirus that causes sporadic
      fatal disease in cats characterized by vasculitis, granulomatous inflammation and
      effusive pleuritis/peritonitis. Histologic changes in lymphoid tissues include
      lymphoid hyperplasia, lymphoid depletion, histiocytosis, and granuloma formation.
      Although viremia occurs, histologic lesions are not found uniformly throughout
      lymphoid tissues. We used experimental infection of cats with a highly pathogenic
      FIPV isolate, UCD8, to study histologic lesions, virus replication, and cytokine
      expression in multiple lymphoid tissues during the effusive phase of disease.
      Viral RNA was found in 76% of central tissues (mediastinal lymph node, spleen,
      mesenteric lymph node) examined, as compared to 27% of peripheral tissues
      (popliteal lymph node, cervical lymph node, femoral bone marrow). All tissues
      positive for virus replication also demonstrated lymphoid depletion. Generally,
      affected tissues had lower levels of IL-4 and IL-12-p40 mRNA and higher levels of
      IL-10 mRNA. Although no differences in IFN-gamma or TNF-alpha mRNA were measured,
      TNF-alpha protein expression was greater in affected tissues and demonstrated a
      shift in the source of TNF-alpha from macrophages to lymphocytes. Together, these
      results colocalize FIPV replication, lymphocyte depletion in tissues, and
      alterations in cytokine transcription and translation. A possible role for TNF
      alpha in the previously described FIPV-induced lymphocyte apoptosis is also
      suggested.

PMID- 14637035
TI  - Prediction of bluetongue vector distribution in Europe and north Africa using
      satellite imagery.
AB  - Bluetongue is an infectious, non-contagious arboviral disease thought to infect
      all known ruminant species. Since 1998, an unprecedented epizootic of the disease
      has occurred in the Mediterranean region, resulting in the deaths of over 800,000
      sheep to date. Bluetongue virus (BTV) is transmitted by biting midges of which
      one species, Culicoides imicola, is the major vector in the old world. C. imicola
      was trapped for 2 years at 87 sites across Portugal and models were developed for
      predicting the presence and abundance of the midge at these sites. Discriminant
      analysis was used to identify the best models from 40 temporally Fourier
      processed 1 km spatial resolution remotely-sensed variables. The best models
      correctly predicted presence and absence at 83 of the 87 sites, and abundance at
      76 sites. The models were then used to predict C. imicola presence and abundance
      elsewhere across Europe and north Africa. C. imicola was predicted to be present
      and in high abundance at the majority of areas affected in the recent bluetongue
      epizootic, including the Balearics, Sardinia, Corsica, Sicily, areas of mainland
      Italy, large areas of Greece, western Turkey and northern Algeria and Tunisia.

PMID- 14637036
TI  - Vaccine efficacy of a cell lysate with recombinant baculovirus-expressed feline
      infectious peritonitis (FIP) virus nucleocapsid protein against progression of
      FIP.
AB  - The Type II feline infectious peritonitis virus (FIPV) infection of feline
      macrophages is enhanced by a monoclonal antibody (MAb) to the S protein of FIPV.
      This antibody-dependent enhancement (ADE) activity increased with the MAb that
      showed a neutralizing activity with feline kidney cells, suggesting that there
      was a distinct correlation between ADE activity and the neutralizing activity.
      The close association between enhancing and neutralizing epitopes is an obstacle
      to developing a vaccine containing only neutralizing epitopes without enhancing
      epitopes. In this study, we immunized cats with cell lysate with recombinant
      baculovirus-expressed N protein of the Type I FIPV strain KU-2 with an adjuvant
      and investigated its preventive effect on the progression of FIP. Cats immunized
      with this vaccine produced antibodies against FIPV virion-derived N protein but
      did not produce virus-neutralizing antibodies. A delayed type hypersensitivity
      skin response to N protein was observed in these vaccinated cats, showing that
      cell mediated immunity against the FIPV antigen was induced. When these
      vaccinated cats were challenged with a high dose of heterologous FIPV, the
      survival rate was 75% (6/8), while the survival rate in the control group
      immunized with SF-9 cell-derived antigen was 12.5% (1/8). This study showed that
      immunization with the cell lysate with baculovirus-expressed N protein was
      effective in preventing the progression of FIP without inducing ADE of FIPV
      infection in cats.

PMID- 14637037
TI  - Oral transmission of porcine reproductive and respiratory syndrome virus by
      muscle of experimentally infected pigs.
AB  - The current study was performed to determine if porcine reproductive and
      respiratory syndrome virus (PRRSV) could be transmitted to pigs by feeding muscle
      tissue obtained from recently infected pigs. Muscle obtained from pigs infected
      with either a European strain (EU donor pigs) or American strain (US donor pigs)
      of PRRSV was fed to PRRSV-free receiver pigs. The donor pigs were slaughtered 11
      days post-infection (dpi). PRRSV was detected by conventional virus isolation in
      muscle at 11 dpi from 7 of 12 EU donor pigs and 5 of 12 US donor pigs. In
      contrast to conventional virus isolation, all muscle samples from infected pigs
      were positive for viral nucleic acid by PCR, except for muscle from one animal
      infected with the American strain of PRRSV. Five hundred grams of raw
      semimembranosus muscle from each of the donor pigs was fed over a 2 days period
      (250 g per day) to each of two receiver pigs (48 receiver pigs). The receiver
      pigs were housed separately in five groups. One of the five groups was fed muscle
      obtained from US donor pigs that was also spiked with the American strain of
      PRRSV. Sentinel pigs were placed in-contact with the group of receiver pigs fed
      spiked muscle. All receiver pigs became viraemic by 6 days post-feeding (dpf).
      There was evidence of horizontal transmission with sentinel pigs, in-contact with
      receiver pigs, becoming viraemic. The study demonstrates that PRRSV could be
      infectious through the oral route via the feeding of meat obtained from recently
      infected pigs.

PMID- 14637038
TI  - Absence of host specificity for in vitro adhesion of probiotic lactic acid
      bacteria to intestinal mucus.
AB  - Adhesion of probiotic lactic acid bacteria (LAB) has been reported to be host
      species specific. Host specificity is regarded as a desirable property for
      probiotic bacteria and therefore recommended as one of the selection criteria.
      However, previous studies have indicated that LAB originating from one host
      adhere well also to the mucus of other species. The aim of the study was to
      investigate the host specificity of LAB adhesion in human, canine, possum, bird
      and fish mucus in vitro. An in vitro mucus adhesion model was utilized in this
      study using immobilized mucus from faeces or intestinal material of these hosts.
      The results indicate that the adhesion trait was not host specific but rather was
      characteristic to LAB species. In conclusion, mucus adhesion properties are more
      dependent on the LAB strain than on the host. This suggests that animal models in
      probiotic adhesion assays may be more applicable to other species than thought
      earlier. Positive health effects facilitated by adherent probiotics in humans may
      also denote the possibility of similar outcome in other species and vice versa.

PMID- 14637039
TI  - Phage types and antimicrobial resistance among Danish bovine Staphylococcus
      aureus isolates since the 1950s.
AB  - A total of 292 bovine Staphylococcus aureus isolates obtained from the 1950s (86
      isolates), 1992 (107 isolates), and 2000 (99 isolates) were examined for
      antimicrobial susceptibility and phage typing. The same types of S. aureus (80,
      52, 3A, 3A/3C, 42E, 77) were found among the isolates from all three time
      periods, representing 43.3% of the typeable isolates. This indicates that the
      Danish S. aureus population related to bovine mastitis has remained relatively
      unchanged over the last 50 years. The occurrence of antimicrobial resistance has
      remained low in Denmark in comparison to other countries in Europe.

PMID- 14637040
TI  - Specificity of two tests for the early diagnosis of bovine paratuberculosis based
      on cell-mediated immunity: the Johnin skin test and the gamma interferon assay.
AB  - Paratuberculosis in cattle is a chronic debilitating infectious disease caused by
      Mycobacterium paratuberculosis. Control of paratuberculosis is based on tests
      that principally detect advanced stages of infections: faecal culture and
      serology. Tests measuring cell-mediated immunity (CMI) could improve control of
      paratuberculosis if able to diagnose mycobacterial infections earlier, before
      animals become infectious. A drawback of CMI tests for paratuberculosis has been
      a reported low specificity. This study re-examined CMI specificity and factors
      that may affect it. The specificities of the Johnin skin test and its in vitro
      equivalent, the gamma interferon (IFNgamma) assay, were estimated in 35
      uninfected dairy herds. In each herd a random sample of 20 young (6-24 months
      old) and 20 adult (> or =24 months old) female dairy cattle were tested by both
      tests simultaneously. Skin test specificity was 93.5% using a skin thickness
      increase of > or =4mm as the cut-off value. IFNgamma assay specificity when
      interpreted using a newly developed algorithm was 93.6%. When interpreted
      according to two alternative algorithms provided by the IFNgamma kit suppliers,
      the assay had specificities of 66.1 and 67.0%. If the skin test and IFNgamma
      assay were used in parallel, and only animals positive on both tests were
      considered as M. paratuberculosis-infected, the specificity was 97.6%. Agreement
      between skin test and IFNgamma assay on 1631 total animals was fair (kappa=0.41).
      Antigen batch influenced the specificity of both the skin test, ranging from 92
      to 95%, and the IFNgamma assay, ranging from 71 to 99% among batches. Test
      specificity also varied among herds ranging from 58 to 100% for the skin test and
      57 to 100% for the IFNgamma assay. While factors affecting CMI test specificity
      and agreement need further evaluation, the high specificity and general agreement
      among these CMI tests, coupled with the excellent results obtained in the control
      of bovine tuberculosis using CMI tests, support their potential value in the
      early diagnosis and control of paratuberculosis.

PMID- 14637041
TI  - Virulence genes of O149 enterotoxigenic Escherichia coli from outbreaks of
      postweaning diarrhea in pigs.
AB  - The goal of this research was to determine whether isolates of O149 porcine
      enterotoxigenic Escherichia coli (ETEC) recovered from recent outbreaks of severe
      diarrhea in weaned pigs in Ontario, Canada, had virulence attributes different
      from those of isolates of the same serogroup from diarrhea of pigs in the 1970s
      and 1980s. Polymerase chain reaction amplification was used to determine the
      distribution of 11 virulence-associated genes in recent (100 isolates) and old
      (35 isolates) Ontario O149 porcine ETEC. These tests demonstrated that 92% of the
      recent isolates possessed the estA gene for STa enterotoxin, whereas none of the
      old isolates had this gene. H antigen determination showed that all the isolates
      which lacked the estA gene (all 35 old isolates plus 8 recent isolates) were H43,
      whereas isolates which had the estA gene were H10. The astA gene for
      enteroaggregative heat-stable enterotoxin (EAST1) and the K88ac antigen were
      present in all 135 isolates. Plasmid analyses identified a cryptic 5.1kb plasmid
      in 99% of recent and 60% of old isolates. Suppressive subtractive hybridization
      associated several types of DNA fragments with the recent O149 ETEC, namely,
      fragments with no homology to DNA in databases, fragments of LPS biosynthesis
      genes, and F plasmid DNA. We conclude that the recent outbreaks of PWD in Ontario
      pigs were associated primarily with a new serotype of O149 ETEC and that isolates
      of this serotype possessed the estA gene that was not present in old O149 ETEC
      isolated from pigs in Ontario.

PMID- 14637042
TI  - Frequency of Shiga toxin-producing Escherichia coli (STEC) isolates among
      diarrheic and non-diarrheic calves in Brazil.
AB  - The occurrence of Shiga toxin (Stx) gene sequences was examined in 344 fecal
      samples from diarrheic (n=139) and non-diarrheic (n=205) calves from 12 beef
      farms in Sao Paulo State, Brazil to study the prevalence of Shiga toxin-producing
      Escherichia coli (STEC) strains. Forty-four (12.7%) animals were found to be
      positive for stx. The frequency of carriage of stx was higher in diarrheic calves
      (28/139, 20%) than in non-diarrheic animals (16/205, 7.8%) (P<0.001). Among the
      24 STEC strains recovered from the animals, 12 isolates carried stx1, four stx2,
      and 8 carried both stx1 and stx2 genes. The eae and the enterohaemolysin (Ehly)
      gene sequences occurred at high frequencies in these STEC strains (41.6 and
      50.0%, respectively). A total of 16 serotypes were identified. The serotypes
      O111:NM (four isolates), O111:H8 (two) and O118:H16 (one), currently described as
      enterohaemorrhagic E. coli (EHEC), were isolated from cattle in Brazil for the
      first time. These findings reinforce the importance of cattle as a reservoir of
      EHEC strains in Brazil.

PMID- 14637043
TI  - Recent advances in molecular epidemiology and detection of Taylorella
      equigenitalis associated with contagious equine metritis (CEM).
AB  - In the present review article, recent molecular advances relating to studies with
      Taylorella equigenitalis, as well as the recently described second species of the
      genus Taylorella, namely Taylorella asinigenitalis, have been described.
      Molecular genotyping of T. equigenitalis strains by pulsed-field gel
      electrophoresis (PFGE) after digestion with the suitable restriction enzyme(s)
      enabled the effective discrimination of strains, thus allowing the examination of
      the scientific mechanism(s) for its occurrence and transmission of contagious
      equine metritis (CEM). Alternatively, polymerase chain reaction (PCR)
      amplification and nucleotide sequencing of the 16S ribosomal DNA sequence and/or
      the other species specific sequence(s) as targets were confirmed to be effective
      for identification of T. equigenitalis. These new analytical methods at the
      genomic DNA level also enabled the discrimination of the newly discovered donkey
      related T. asinigenitalis from T. equigenitalis, and moreover, the performance of
      phylogenetic analysis of genus Taylorella organisms with other closely related
      genera. Furthermore, detailed analysis of the genes responsible for CEM within
      the T. equigenitalis genome would be useful to help elucidate the pathogenic
      virulence and transmission mechanisms associated with the important equine
      pathogen associated with CEM.

PMID- 14637044
TI  - Epidemiology of Mycobacterium bovis infections of pigs and wild boars using a
      molecular approach.
AB  - A molecular epidemiological approach was applied to establishing a possible role
      for the wild boar as a natural reservoir of Mycobacterium bovis in Sierra de
      Villuercas, Western Spain; an area free of farmed cattle and wild deer
      populations. Spoligo and VNTR typing were used over a three year period to study
      the epidemiological relationship between the occurrence of bovine tuberculosis
      (TB) in extensively bred Iberian pigs and indigenous wild boar. The 37 sampled
      wild boar showed different degree of calcified granulomatous lesions in
      retropharyngeal, mediastinal and pulmonary lymph nodes. The 25 sampled Iberian
      pigs showed calcified lesions, mainly in the respiratory tract. Lesions located
      in the mesenteric lymph nodes appeared secondarily. M. bovis was isolated from
      all affected animals. Twenty-five and 37 isolates of M. bovis were obtained from
      domestic pigs and wild boar, respectively. Our findings provide evidence that
      supports the possibility of cross infection between wild boar and domestic pig
      populations. This is contrary to the generally held belief that swine represent
      an epidemiological dead end host and play no role in the epidemiology of M.
      bovis.

PMID- 14637045
TI  - Epidemiology of Streptococcus suis serotype 5 infection in a pig herd with and
      without clinical disease.
AB  - The aim of this study was to describe the transmission and the kinetics of the
      infection caused by Streptococcus suis serotype 5 in a multisite farrow-to-finish
      pig herd. Most sows carried S. suis serotype 5 in their vaginal tract, but not in
      their nasal cavities, as demonstrated by immunomagnetic separation (IMS)
      technique. Their offspring became infected during farrowing, confirming vertical
      transmission. During the first 4 weeks of life, a low number of piglets were
      carriers of S. suis serotype 5 in their nasal cavities. However, when clinical
      signs appeared, the carrier rate significantly increased, suggesting that
      isolation from nasal cavities is a better indication of active transmission than
      of a carrier state. Clinical cases were present in animals between 4 and 8 weeks
      of age, when maternal antibodies were at their lowest level. Up to six different
      genotypes of the same serotype could be identified by random amplified
      polymorphic DNA; however, a single clone was responsible for all clinical cases
      studied. This clone could only be isolated from a single sow, indicating that its
      prevalence in breeding animals was low. Interestingly, 1 year later, clinical
      disease associated with S. suis serotype 5 spontaneously disappeared. At that
      time, the genotype responsible for the clinical signs was not detected in the
      herd and the levels of antibodies in sows and maternal antibodies in piglets were
      not higher than those of the previous year.

PMID- 14637046
TI  - Research on infectious bursal disease--the past, the present and the future.
AB  - Infectious bursal disease (IBD) virus (IBDV) is the etiological agent of "Gumboro
      disease". Although first observed about 40 years ago, this disease continues to
      pose an important threat to the commercial poultry industry. The emergence of
      antigenic variant as well as very virulent strains in vaccinated flocks
      considerably stimulated research efforts on both, IBD and IBDV. In this review,
      some of the recent advances in the understanding of the structure, morphogenesis
      and molecular biology of the virus as well as in development of new diagnostic
      approaches and new strategies for vaccination against IBD are briefly summarized.

PMID- 14637047
TI  - Development of a PCR for specific detection of Mycoplasma bovis from bovine milk
      and mucosal samples: a critique.

PMID- 14637049
TI  - A proposed mechanism which may explain why the fetus is not considered to be
      foreign tissue by the maternal system during pregnancy.
AB  - A review of laboratory and clinical data is presented which supports a proposed
      endemic control mechanism designed to destroy the initiation of any localized
      abnormal growth of cells regardless of whether the cells are normal or aberrant.
      The emphasis of this article hypothesizes how the endemic control mechanism
      distinguishes between a fertilized ovum and fetus--which are also foreign to the
      mother's system--so that the fetus is not rejected by the endemic control
      mechanism that destroys other types of localized abnormal cell growth in the
      body. These data support a commonality between endemic control of pregnancy,
      tissue repair, and cancer growth and development.

PMID- 14637050
TI  - A continuous model of biomass size spectra governed by predation and the effects
      of fishing on them.
AB  - A new time-dependent continuous model of biomass size spectra is developed. In
      this model, predation is the single process governing the energy flow in the
      ecosystem, as it causes both growth and mortality. The ratio of predator to prey
      is assumed to be distributed: predators may feed on a range of prey sizes. Under
      these assumptions, it is shown that linear size spectra are stationary solutions
      of the model. Exploited fish communities are simulated by adding fishing
      mortality to the model: it is found that realistic fishing should affect the
      curvature and stability of the size spectrum rather than its slope.

PMID- 14637051
TI  - Sampling effects and the robustness of quantitative and qualitative food-web
      descriptors.
AB  - Food-web descriptors serve as a means for among-web comparisons that are
      necessary for the discovery of regularities in respect to food-web structure.
      Qualitative descriptors were however found to be highly sensitive to varying
      levels of sampling effort. To circumvent these shortcomings, quantitative
      counterparts were proposed which take the magnitude of trophic interaction
      between species into consideration. For 14 properties we examined the performance
      with increasing sampling effort of a qualitative, an unweighted quantitative
      (giving the same weight to each taxon), and a weighted quantitative version
      (weighing each taxon by the amount of incoming and outgoing flows). The
      evaluation of 10 extensively documented quantitative webs formed the basis for
      this analysis. The quantitative versions were found to be much more robust
      against variable sampling effort. This increase in accuracy is accomplished at
      the cost of a slight decrease in precision as compared to the qualitative
      properties. Conversely, the quantitative descriptors also proved less sensitive
      to differences in evenness in the distribution of link magnitude. By more
      adequately incorporating the information inherent to quantitative food-web
      compilations, quantitative descriptors are able to better represent the web, and
      are thus more suitable for the elucidation of general trends in food-web
      structure.

PMID- 14637052
TI  - A mathematical model of the methionine cycle.
AB  - Building on the work of Martinov et al. (2000), a mathematical model is developed
      for the methionine cycle. A large amount of information is available about the
      enzymes that catalyse individual reaction steps in the cycle, from methionine to
      S-adenosylmethionine to S-adenosylhomocysteine to homocysteine, and the removal
      of mass from the cycle by the conversion of homocysteine to cystathionine.
      Nevertheless, the behavior of the cycle is very complicated since many substrates
      alter the activities of the enzymes in the reactions that produce them, and some
      can also alter the activities of other enzymes in the cycle. The model consists
      of four differential equations, based on known reaction kinetics, that can be
      solved to give the time course of the concentrations of the four main substrates
      in the cycle under various circumstances. We show that the behavior of the model
      in response to genetic abnormalities and dietary deficiencies is similar to the
      changes seen in a wide variety of experimental studies. We conduct computational
      "experiments" that give understanding of the regulatory behavior of the
      methionine cycle under normal conditions and the behavior in the presence of
      genetic variation and dietary deficiencies.

PMID- 14637053
TI  - Nest architecture, activity pattern, worker density and the dynamics of disease
      transmission in social insects.
AB  - The role of disease in the organization of insect colonies has become an
      important focus of research in evolutionary pathobiology, in which the
      relationship of sociality and disease transmission can be comparatively and
      experimentally analysed. In this paper we use an individual-based model of
      disease transmission to assess how an epidemic is influenced by worker density
      and activity level, the probability of disease transmission, and the structural
      organization of the nest. First, we observed in our model a nonlinear interaction
      between worker density and the probability of disease transmission: high levels
      of both factors interact to enhance the likelihood of an epidemic. Additionally,
      when we incorporated in our model the empirical observation that only a fraction
      of the worker population in social insect colonies is active at any given point
      in time, results suggested that relatively low levels of worker movement can have
      a significant impact on the spread of disease, slowing its transmission through
      the colony. Finally, we found that nests having even a simple spatial separation
      of chambers could delay the spread of infection and diminish the severity of an
      outbreak. The effect of nest structure in delaying infection spread became more
      pronounced as nest architecture became increasingly unidimensional, as in the
      case of simple gallery nests. Therefore, nest architecture and worker activity
      patterns might indeed exert considerable influence on the dynamics of epidemics
      in social insects and should be incorporated into models of disease transmission.

PMID- 14637054
TI  - A computational model for collagen fibre remodelling in the arterial wall.
AB  - As the interaction between tissue adaptation and the mechanical condition within
      tissues is complex, mathematical models are desired to study this interrelation.
      In this study, a mathematical model is presented to investigate the interplay
      between collagen architecture and mechanical loading conditions in the arterial
      wall. It is assumed that the collagen fibres align along preferred directions,
      situated in between the principal stretch directions. The predicted fibre
      directions represent symmetrically arranged helices and agree qualitatively with
      morphometric data from literature. At the luminal side of the arterial wall, the
      fibres are oriented more circumferentially than at the outer side. The discrete
      transition of the fibre orientation at the media-adventitia interface can be
      explained by accounting for the different reference configurations of both
      layers. The predicted pressure-radius relations resemble experimentally measured
      sigma-shaped curves. As there is a strong coupling between the collagen
      architecture and the mechanical loading condition within the tissue, we expect
      that the presented model for collagen remodelling is useful to gain further
      insight into the processes involved in vascular adaptation, such as growth and
      smooth muscle tone adaptation.

PMID- 14637055
TI  - New equations for redox and nano-signal transduction.
AB  - Cells maintain redox potentials (Eh) in intracellular compartments, sometimes
      referred to as redox environments. These potentials are often very reducing, for
      example in the cytoplasm, but throughout the cell different potentials are
      maintained, commensurate with the functionality of that particular part of the
      cell. Furthermore, within a simple cellular compartment, "hot-spots" of redox
      poise may be maintained. However, despite this complexity, the quantification of
      such redox potentials has been attempted, and there is indeed a need to
      accurately assess such potentials, and to monitor how they might change with
      time. Changes in intracellular potentials may control the oxidation or reduction
      of protein residues, such as cysteine, which would alter the conformation of
      those proteins and so modulate their function. Although there are several methods
      for estimating the intracellular redox potential, the most accessible technique
      is the measurement of intracellular concentrations of GSH and GSSG, and the
      calculation of Eh using the Nernst equation. However, using this equation shows
      that the Eh imposed by the glutathione couple is dependent on the total
      concentration of glutathione present, and therefore values of Eh obtained may be
      erroneous. Here, we suggest new equations that can be used to calculate the redox
      environments of cells.

PMID- 14637056
TI  - Drastic growth effect may explain sympatric cannibalistic polymorphism.
AB  - Cannibalistic polyphenism is observed in many fishes and amphibians. In the case
      of amphibian larvae, cannibal morph and typical morph coexist. Benefits and costs
      of the cannibal morph have been studied empirically but the mechanism of the
      maintenance of polymorphism is not well known. Here, we construct a game model of
      typical and cannibal morph strategies to obtain the condition of stable
      coexistence. Generally, once an individual succeeds in cannibalism, it grows very
      quickly, which facilitates the next cannibalism. In a model without this 'drastic
      growth effect', stable coexistence cannot occur. To represent drastic growth
      effect, it is assumed that cannibal/typical morph stage is followed by
      giant/normal stage. A cannibal morph that performs cannibalism in the first stage
      can become a 'giant' in the next stage. This model allows stable coexistence of
      cannibal and typical morphs. The condition for coexistence is that payoff of a
      giant is two times larger than normal individuals. As long as direct consumption
      of victim's body is considered as reward for successful cannibalism, coexistence
      cannot be explained. When the reward is considered as social standing of being
      outstanding size in a population, sympatric cannibalistic polymorphism is
      possible, without regard to the initial size variation or resource shortage.

PMID- 14637057
TI  - Variant evolutionary trees under phenotypic variance.
AB  - Evolutionary branching, which is a coevolutionary phenomenon of the development
      of two or more distinctive traits from a single trait in a population, is the
      issue of recent studies on adaptive dynamics. In previous studies, it was
      revealed that trait variance is a minimum requirement for evolutionary branching,
      and that it does not play an important role in the formation of an evolutionary
      pattern of branching. Here we demonstrate that the trait evolution exhibits
      various evolutionary branching paths starting from an identical initial trait to
      different evolutional terminus traits as determined by only changing the
      assumption of trait variance. The key feature of this phenomenon is the
      topological configuration of equilibria and the initial point in the manifold of
      dimorphism from which dimorphic branches develop. This suggests that the existing
      monomorphic or polymorphic set in a population is not an unique inevitable
      consequence of an identical initial phenotype.

PMID- 14637058
TI  - The origin of the tRNA molecule: implications for the origin of protein
      synthesis.
AB  - A model for tRNA molecule origin is discussed. The model postulates that this
      molecule originated simply by direct duplication (and subsequent evolution) of a
      gene coding for an RNA hairpin structure, which can thus be hypothesized as the
      evolutionary precursor of the tRNA molecule. The main properties are defined for
      these hairpin structures and it is suggested that these structures might have
      housed, near their 3' end, anticodons that were transferred to the loop of the
      tRNA anticodon during duplication of the hairpin structures. Moreover, the main
      characteristics are given for the evolutionary intermediary formed by direct
      duplication of the hairpin structure, i.e. the double hairpin. The evolutionary
      stages envisaged by this model for tRNA origin seem to naturally imply some
      evolutionary transitions through which the origin of protein synthesis passed.
      Finally, some strong historical evidence is provided to corroborate the model.

PMID- 14637059
TI  - Complex patterns of viral load decay under antiretroviral therapy: influence of
      pharmacokinetics and intracellular delay.
AB  - We present a model of HIV dynamics under antiretroviral therapy that combines
      drug pharmacokinetics and intracellular delay. A two compartment pharmacokinetic
      model is employed to determine the time evolution of the intracellular
      concentrations of the active forms of drugs, and thereby drug efficacy. The viral
      replication period is divided into pre- and post-drug action parts, allowing for
      the introduction of an intracellular delay in drug action. The standard model of
      viral dynamics is modified to account for the drug dependence of intracellular
      delay and continuously varying drug efficacy. Model calculations reveal that
      viral load decay in HIV infected patients under monotherapy can exhibit
      remarkably complex patterns depending on the relative magnitudes of the
      pharmacokinetic, intracellular, and intrinsic viral dynamic time-scales. The
      commonly assumed exponential decay is only a special case. However, uncertainties
      in measurement and the low sampling frequencies employed in present clinical
      studies preclude the identification of these patterns from existing clinical
      viral load data.

PMID- 14637060
TI  - Fluctuations in transcription factor binding can explain the graded and binary
      responses observed in inducible gene expression.
AB  - Inducible genes are expressed in the presence of an external stimulus. Individual
      cells may exhibit either a binary or graded response to such signals. It has been
      hypothesized that the chemical kinetics of transcription factor/DNA interactions
      can account for both these scenarios (EMBO J. 9(9) (1990) 2835; BioEssays 14(5)
      (1992) 341). To explore this question, we have conducted work based on the
      experimental results of Fiering et al. (Genes Dev. 4 (10) (1990) 1823). In these
      experiments, three upstream NF-AT binding sites control transcription of the lacZ
      gene, which codes for the enzyme beta-Galactosidase. The experimental data show a
      binary response for this system. We consider the effects of fluctuations in NF-AT
      binding on the response of the system. Our modeling results are in good
      qualitative agreement with the experimental data, and illustrate how the binary
      and graded responses can stem from the same underlying mechanism.

PMID- 14637061
TI  - Er:YAG laser osteotomy directed by sensor controlled systems.
AB  - BACKGROUND: Great efforts have been taken in the past to develop laser systems
      suitable for bone cutting. Laser systems emitting light in the infrared spectrum
      (2.9, 3.0 microm) have been found to be ideal for efficient bone ablation with
      very little carbonization. AIM: To evaluate a new laser bone cutting system
      enabling the automatic detection of different tissue qualities by an integrated
      sensor to avoid damage to sensitive structures such as blood vessels or nerves.
      MATERIAL: An Erbium:YAG laser containing an integrated closed-loop control
      system, was constructed and tested on dissected bone. Process emissions such as
      resonance changes caused by the interaction of laser light and various tissue
      structures can be used for a controlled system. Sensor signals from a photodiode
      and a piezo-electric accelerometer were received and processed to guide the laser
      osteotomy. METHODS: Tests were performed on dissected bone specimens from rabbit
      femur (14) and minipig jaw (6). After laser application, the bone specimens were
      evaluated macroscopically and histologically. RESULTS: The specimens were
      evaluated histomorphometrically for the depth of cortical bone ablation when the
      closed-loop control system switched off the laser. Mean courses of 97.45% (pig)
      and 97.83% (rabbit) showed that the systems work with precision. CONCLUSION:
      After penetrating the cortical bone layer, the laser beam was promptly
      interrupted due to extreme changes of the signal character received by the sensor
      system. The in vitro tests of this new laser closed-loop control system were
      successful.

PMID- 14637062
TI  - Nasolabial and alveolar morphology following presurgical orthopaedic treatment in
      complete unilateral clefts of lip, alveolus and palate.
AB  - INTRODUCTION: The purpose of this study was to assess the three-dimensional (3-D)
      facial and alveolar morphology of patients with unilateral clefts of lip,
      alveolus and palate by means of a computer-aided diagnosis system. PATIENTS AND
      METHODS: Maxillary orthopaedic treatment was performed using soft/hard acrylic
      plates (Hotz's) within 2 weeks of birth. The nasolabial and alveolar morphology
      of 15 patients was evaluated before orthopaedic treatment (2 weeks of age) and
      before cheiloplasty (3 months of age). Nasolabial form was measured using a 3-D
      optical scanner. Twenty-one landmarks were extracted from the data and analysed
      linearly and angularly. Alveolar forms were measured with a high-accuracy contact
      type 3-D digitizer on plaster casts. Seven landmarks were digitized and analysed
      linearly and angularly. RESULTS: Some growth was observed in the intercanthal
      distance, alar width, intercommissural width, and height of the lip. There was
      little change in the width of the cleft lip or displacement of the columella
      base, while the alveolar cleft narrowed. CONCLUSION: Presurgical orthopaedics
      reduces cleft width and makes subsequent surgery easier.

PMID- 14637063
TI  - Intravelar veloplasty in cleft lip, alveolus and palate and outcome of speech and
      language acquisition: a prospective study.
AB  - BACKGROUND: Speech and language acquisition are major, important criteria in the
      treatment outcomes of cleft lip and palate patients. A generally accepted and
      definitive treatment protocol regarding surgical techniques and the time schedule
      does not yet exist. In the world literature, there are reports of velo-pharyngeal
      insufficiency rates between 7 and 30%. PURPOSE: In a prospective study, all
      children aged 312 months with cleft lip, alveolus and palate, or cleft palate
      only, underwent an intravelar veloplasty. Follow-up monitoring consisted of
      frequent clinical linguistic checks and supervision of language development
      without a planned intention of articulation therapy before the age of about 5
      years. RESULTS: Three hundred and ninety-seven children with non-syndromic clefts
      were included in this study, the youngest being 8-year old. Sixty children (15%)
      showed deviations in language and speech acquisition. From these, 56 (14%) had
      received articulation therapy after the 5th birthday. From these 56 children, 45
      had overcome their problems with speech therapy alone whereas 11 (3%) needed a
      velo-pharyngeoplasty. DISCUSSION: Although these results are much better than
      those reported in other cohorts, some children still have velo-pharyngeal
      incompetence for no apparent reason. One possible explanation might be surgical,
      since on occasions, the intravelar muscle bundle is divided into two parts and
      the palato-pharyngeal part runs isolated more laterally and can be missed during
      reconstruction and retropositioning.

PMID- 14637064
TI  - Immunohistochemical observations of cellular differentiation and proliferation in
      endochondral bone formation from grafted periosteum: expression and localization
      of BMP-2 and -4 in the grafted periosteum.
AB  - PURPOSE: To clarify the involvement of bone morphogenetic proteins (BMPs) in the
      proliferation and differentiation of osteo/chondrogenic cells during the process
      of bone formation from grafted periosteum. MATERIAL AND METHODS: Tibial
      periosteum of young Japanese white rabbits was grafted into suprahyoid muscles
      and removed after 7, 9, 14 or 21 days. BMP-2, -4, proliferative cell nucleus
      antigen (PCNA) immunoreaction and Alcian blue staining in grafted periosteum was
      then sought microscopically. RESULTS: PCNA positive cells in the grafted
      periosteum expressed BMP-2 at 7 days. These cells differentiated into
      chondroblasts that expressed BMP-2 and Alcian blue at 9 days. After 14 days,
      cartilage formation was seen, and BMP-2 and -4 expressions were observed in
      mature and hypertrophic chondrocytes. Endochondral ossification was observed at
      21 days and osteoblasts showed both BMP-2 and -4 expression. CONCLUSION: Both BMP
      2 and -4 appear to play regulatory roles in the process of endochondral
      ossification from grafted periosteum, due to their involvement in the
      proliferation and differentiation into chondrogenic and osteogenic cells.

PMID- 14637065
TI  - Relative en- and exophthalmometry in zygomatic fractures comparing optical non
      contact, non-ionizing 3D imaging to the Hertel instrument and computed
      tomography.
AB  - AIM: It is the aim of the present study to introduce non-contact, non-invasive
      optical 3D imaging to relative exophthalmometry and to compare the resulting data
      to exophthalmometry values assessed by the Hertel instrument and computed
      tomography. PATIENTS AND METHODS: 20 patients (3 female, 17 male, 44.4+/-16.6
      years) without orbital pathology, who were examined by computed tomography of
      head and neck for the exclusion of different diseases, and seven patients (1
      female, 6 male, 40.1+/-14.4 years), who received routine orbital computed
      tomography because of zygomatic fractures, were included in the study. Optical 3D
      images of the facial surface were assessed and Hertel exophthalmometry was
      carried out to determine the relative globe position. In patients with zygomatic
      fractures the assessment of optical 3D images and Hertel values was repeated 5
      days after surgery. RESULTS: For patients without orbital pathology relative
      exophthalmometry data were 1.4+/-1.1 mm for the Hertel instrument, 0.9+/-1.0 mm
      for computed tomography and 0.5+/-0.5 mm for optical 3D imaging. The values for
      Hertel exophthalmometry and computed tomography did not differ statistically
      significantly (p(Herteldifferencepreop/CTdifferencepreop)=0.284), while there was
      a significant difference between Hertel exophthalmometry and optical 3D imaging
      (p(Herteldifferencepreop/opticaldifferencepreop)=0.008). In the cases of
      zygomatic fractures, Hertel exophthalmometry revealed less pronounced relative
      differences in globe position than CT and optical 3D imaging data (Hertel 0.7+/
      1.1 mm, CT 1.9+/-1.0 mm, optical 3D imaging 1.9+/-1.0 mm). Postoperatively,
      relative Hertel exophthalmometry showed an increased value revealing a more
      pronounced enophthalmos (1.7+/-1.0 mm), while the corresponding value of the
      optical 3D images decreased as a sign for normalization of the globe position
      (1.1+/-0.7 mm). CONCLUSION: Because of its reliance on the lateral orbital rims
      Hertel exophthalmometry can lead to an under- or overestimation of enophthalmos,
      when soft tissue oedema or a dislocation of the orbital rim are present. The
      combination of computed tomography as baseline measurement and optical 3D imaging
      for the follow-up examinations reveal more realistic data in cases of zygomatic
      fractures. Therefore, they should be preferred to the determination of Hertel
      values especially in more complex cases.

PMID- 14637066
TI  - Teratomas of the head and neck region.
AB  - BACKGROUND: Teratomas are exceptionally rare malformations in the head and neck
      region. They are mostly benign but as a direct result of their rarity, most
      clinician's experience of these tumours is very limited, and consequently most of
      the associated literature consists of single case reports. In this paper,
      however, all the cases managed by a major Craniofacial Unit (the Australian
      Craniofacial Unit) were reviewed to attempt to identify common problems
      encountered in their management. MATERIAL AND METHODS: All cases managed by the
      Australian Craniofacial Unit over the last 25 years were reviewed. In total a
      series of nine cases was identified, but two were seen and operated on in
      overseas centres and the data in these cases were incomplete, and have been
      excluded from the study. Case note, radiology and pathology review was undertaken
      to collect data. RESULTS: In total a series of seven cases was identified as
      suitable for inclusion in this study. Six of these have had a minimum of 9 years
      follow-up, three having completed growth. CONCLUSION: The initial and subsequent
      management demonstrates that these tumours when benign can be successfully
      removed, but depending on the affected site may require continued
      multidisciplinary management until growth has finished.

PMID- 14637067
TI  - Central acinic cell carcinoma of the mandible. Case report.
AB  - Central acinic cell carcinoma (of the mandible) is rare, and, to our knowledge,
      only seven cases of this disease have been reported in the literature. A case in
      a 67-year-old Japanese woman is presented. Clinical examination revealed a
      10.0x6.0mm mass located on the buccal aspect of the gingiva of the second molar
      in the left mandible. Radiographic examination revealed a radiolucency from the
      second to the third molar of the left mandible. Computed tomography disclosed
      destruction of the lingual cortical bone of the third molar region. The
      preliminary diagnosis was of odontogenic tumour. The patient was admitted, and
      removal of the tumour and of the involved teeth were carried out. Histological
      examination disclosed the diagnosis of acinic cell carcinoma. Subsequently, the
      tumour area was widely excised from the second premolar region to the coronoid
      process, and radical neck dissection was performed. A lymph node metastasis was
      found in the submandibular region. No recurrence or metastasis was observed
      during the 34-month follow-up.

PMID- 14637068
TI  - Indication for and technical refinements of submental intubation in oral and
      maxillofacial surgery.
AB  - INTRODUCTION: In maxillofacial injuries, a choice has often to be made between
      different ways of intubation when surgical access to both the nasal and the oral
      cavities is necessary. Submental intubation is an interesting alternative to
      tracheotomy, especially when short-term postoperative control of the airway is
      foreseeable, and as control of the dental occlusion is complete, and access to
      the nose and mouth is undisturbed. MATERIAL: This kind of intubation has been
      used in our department in 25 cases since 1997. All patients had fractures
      disturbing the dental occlusion plus either an associated fracture of the skull
      base, or a displaced nasal fracture. RESULTS: There was no intra-operative
      complication, average intubation duration was 1.5 days. Post-operative
      complications consisted of one case with hypertrophic scarring and two cases of
      abscess formation in the floor of the mouth. All these completely healed
      following local conservative treatment. CONCLUSION: Submental intubation demands
      certain technical skills but it is simple, rapid and may avoid tracheotomy in
      selected patients.

PMID- 14637069
TI  - Role of GABA(A) receptor-mediated inhibition in the pathogenesis of generalized
      seizures.

PMID- 14637070
TI  - Neuronal intermediate filament overexpression and neurodegeneration in transgenic
      mice.

PMID- 14637072
TI  - Rod genesis in the teleost retina as a model of neural stem cells.

PMID- 14637071
TI  - Long-term L-DOPA therapy: challenges to our understanding and for the care of
      people with Parkinson's disease.

PMID- 14637073
TI  - Adenosine A2A antagonists: potential preventive and palliative treatment for
      Parkinson's disease.

PMID- 14637074
TI  - Norepinephrine and serotonin axonal dynamics and clinical depression: a
      commentary on the interaction between serotonergic and noradrenergic axons during
      axonal regeneration.

PMID- 14637075
TI  - Synuclein aggregation: possible role in traumatic brain injury.

PMID- 14637076
TI  - Can the brain be protected through exercise? Lessons from an animal model of
      parkinsonism.
AB  - Evidence suggests that following injury the brain has the capacity for self
      repair and that this can be promoted through a variety of experiences including
      motor activity. In their article, Dobrossy and Dunnett have provided further
      evidence that this is the case in an animal model in which an excitotoxin is
      applied to the neostriatum. Under standard conditions, such a toxin would cause
      considerable damage to the GABAergic cells of this region and produce behavioral
      deficits. This model has been used to explore certain aspects of Huntington's
      disease, which also involves the loss of these neurons. However, Dobrossy and
      Dunnett show that the damage can be reduced by prior motor training. We have been
      exploring the neuroprotective effects of motor exercise in a different model, one
      involving 6-hydroxydopamine, which normally destroys dopamine neurons. Our
      results indicate that forced exercise can reduce the vulnerability of dopamine
      neurons to 6-hydroxydopamine. The results further suggest that this protection is
      due in part to an increase in the availability of the trophic factor GDNF, which
      can in turn stimulate certain signaling cascades, including one that activates
      ERK. Our results, together with those of Dobrossy and Dunnett and others, raise
      the possibility that exercise will protect against a variety of neurodegenerative
      conditions.

PMID- 14637077
TI  - Stretching the truth. Why hippocampal neurons are so vulnerable following
      traumatic brain injury.

PMID- 14637078
TI  - The role of the peripheral nervous system in immune cell recruitment.

PMID- 14637079
TI  - Welcome to the complex disease world. Alpha2-macroglobulin and Alzheimer's
      disease.

PMID- 14637080
TI  - Brain as the Sea of Marrow.

PMID- 14637081
TI  - Toward cell replacement therapy: promises and caveats.
AB  - Studies in animal models have suggested a role for stem cells in repair and
      regeneration of the nervous system. Human equivalents of stem and precursor cells
      have been isolated and their efficacy is being evaluated in rodent and primate
      models. Difficulties exist in translating results of these preclinical models to
      therapy in humans. Evolutionary differences among rodents, primates, and humans;
      fundamental differences in the anatomy and physiology; differences in immune
      responses in xenotransplant models; the paucity of good transplant models of
      chronic disease; and allelic variability in the cells themselves make any study
      evaluating the efficacy of cells in transplant models difficult to interpret. As
      no better alternatives to testing in animals exist, we suggest that at this early
      stage a considered step-by-step approach to testing and comparison of different
      transplant strategies in isolation will prepare us better for clinical trials
      than simple evaluation of functional outcomes in various models of disease. We
      emphasize that we do not recommend delaying or abandoning clinical trials;
      rather, we suggest that one anticipate failures and design experiments and data
      collection such that we learn from these failures to ensure future success in as
      rapid a time frame as possible.

PMID- 14637082
TI  - Induction of neuronal markers in bone marrow cells: differential effects of
      growth factors and patterns of intracellular expression.
AB  - Bone marrow cells (BMC) can be induced to express neuronal phenotypic features in
      vitro, but the extent to which they can transdifferentiate to mature, functional
      neurons is uncertain. We examined the effects of different growth factors and
      combinations thereof on the expression of neuronal marker proteins in cultures of
      BMC enriched in marrow stromal cells. Patterns of neuronal marker expression
      varied depending on the growth factor or factors to which BMC cultures were
      exposed. Cultures treated for up to 5 weeks with epidermal growth factor,
      fibroblast growth factor-2, retinoic acid, and nerve growth factor displayed
      neuron-like cellular processes and expressed neuronal markers, including the
      neuronal nuclear antigen NeuN, microtubule-associated protein 2, tau,
      synaptophysin, alpha(1A) and alpha(1B) calcium channel subunits, NR2A glutamate
      receptor subunits, and gamma-aminobutyric acid. However, the intracellular
      distribution of these markers was distinct from their usual distribution in
      mature neurons. We conclude that a variety of growth factors can drive BMC toward
      a neuronal phenotype or phenotypes, but that morphological neuronal features and
      the ectopic expression of neuronal proteins and neurotransmitters may not equate
      with the ability to execute normal neuronal functions.

PMID- 14637083
TI  - Investigation of the migration path for new rod photoreceptors in the adult
      cichlid fish retina.
AB  - In the retina of adult teleost, precursor cells divide in the outer nuclear layer
      and give rise to new rod photoreceptors. These new rods migrate from the outer
      limiting membrane to the inner edge of the outer nuclear layer (ONL) before
      differentiating. In order to understand which cues these cells use during
      migration and insertion at the appropriate location we combined cell-specific
      stains in the retina of the cichlid fish Haplochromis burtoni, viewed with
      confocal laserscan microscopy: Dividing cells were labeled with bromodeoxyuridine
      (BrdU), Muller glial cells, cone photoreceptors, and horizontal cells were
      detected by specific antibodies. During the migration phase (24 to 48 h after
      BrdU uptake) up to 46% of BrdU-labeled cells were spindle shaped and radially
      oriented. Most of them were in direct proximity to Muller cell processes. Four
      days after BrdU-uptake, most labeled cells (91%) were found in the inner portion
      of the ONL and displayed a spherical shape. This marks the end of the movement of
      the new rods. At this stage, the labeled cells showed no preference to lie near
      glial fibers but were often found close to the pedicles of double cones. The
      leading edge of migrating cells reached into the outer plexiform layer (OPL) but
      not further than processes of horizontal cells. This is beyond the location of
      mature rods. We hypothesize that the cells are repelled in the OPL and insert
      back in the ONL to differentiate as rods.

PMID- 14637084
TI  - Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal
      cord stimulates sprouting, partially rescues axotomized red nucleus neurons from
      loss and atrophy, and provides limited regeneration.
AB  - Ex vivo gene therapy, utilizing modified fibroblasts that deliver BDNF or NT-3 to
      the acutely injured spinal cord, has been shown to elicit regeneration and
      recovery of function in the adult rat. Delayed grafting into the injured spinal
      cord is of great clinical interest as a model for treatment of chronic injury but
      may pose additional obstacles that are not present after acute injury, such as
      the need to remove an established scar, increased retrograde cell loss and/or
      atrophy, and diminished capacity for regeneration by neurons which may be doubly
      injured. The purpose of the present study was to determine if delayed grafting of
      neurotrophin secreting fibroblasts would have anatomical effects similar to those
      seen in acute grafting models. We grafted a mixture of BDNF and NT-3 producing
      fibroblasts or control fibroblasts into a complete unilateral cervical
      hemisection after a 6-week delay. Fourteen weeks after delayed grafting we found
      that both the neurotrophin secreting fibroblasts and control fibroblasts
      survived, but that only the neurotrophin secreting grafts provided a permissive
      environment for host axon growth, as indicated by immunostaining for RT-97, a
      marker for axonal neurofilaments, GAP-43, a marker for elongating axons, CGRP, a
      marker for dorsal root axons, and 5-HT, a marker for raphe spinal axons, within
      the graft. Anterograde tracing of the uninjured vestibulospinal tract showed
      growth into neurotrophin producing transplants but not into control grafts, while
      anterograde tracing of the axotomized rubrospinal tract showed a small number of
      regenerating axons within the genetically modified grafts, but none in control
      grafts. The neurotrophin expressing grafts, but not the control grafts,
      significantly reduced retrograde degeneration and atrophy in the injured red
      nucleus. Grafts of BDNF + NT-3 expressing fibroblasts delayed 6 weeks after
      injury therefore elicit growth from intact segmental and descending spinal
      tracts, stimulate modest regenerative growth by rubrospinal axons, and partially
      rescue axotomized supraspinal neurons and protect them from atrophy. The
      regeneration of rubrospinal axons into delayed transplants was much less than has
      been observed when similar transplants were placed acutely into a lateral
      funiculus or, after a 4-week delay, into a hemisection lesion. This suggests that
      the regenerative capacity of chronically injured red nucleus neurons was markedly
      diminished. The increased GAP43 reactivity in the corticospinal tracts
      ipsilaterally and contralaterally to the combination grafts suggests that these
      axons remain responsive to the neurotrophins, that the neurotrophins may
      stimulate both regenerative and sprouting responses, and that the grafted cells
      continue to secrete the neurotrophins.

PMID- 14637085
TI  - Delayed transplantation of fibroblasts genetically modified to secrete BDNF and
      NT-3 into a spinal cord injury site is associated with limited recovery of
      function.
AB  - Delivery of neurotrophic factors in acute models of spinal cord injury in adult
      rats can rescue axotomized neurons, promote axonal growth, and partially restore
      function. The extent to which repair and recovery of function can be achieved
      after chronic injury has received less attention. In the companion paper we show
      that transplanting fibroblasts genetically modified to produce neurotrophic
      factors into chronic (6-week) hemisection injuries results in sprouting, partial
      neuroprotection, but only limited regeneration. Here we describe functional
      consequences of this treatment using a series of behavioral tests. Adult rats
      received a complete unilateral C3/C4 hemisection and recovery from the injury was
      assessed over 5 weeks. At 6 weeks postoperative, the experimental group received
      grafts of a combination of fibroblasts modified to secrete BDNF or NT-3. The
      operated control groups received grafts of either gelfoam or gelfoam with
      fibroblasts expressing GFP into the lesion site. Behavioral recovery in the three
      groups was assessed over the next 10 weeks. Severe deficits with no recovery in
      any of the groups were observed in several tests (BBB, limb preference, narrow
      beam, horizontal rope test) that measure primarily motor function. Recovery was
      observed in the grid test, a measure of sensorimotor function, and the von Frey
      test, a measure of response to mechanical stimulation, but there were no
      differences between the operated control or experimental groups. Both groups also
      showed recovery from heat-induced hyperalgesia, with the experimental group
      exhibiting greater recovery than the operated control groups. In this test,
      delivery of neurotrophic factors from transplanted fibroblasts does not worsen
      responses to nociceptive stimuli and in fact appears to reduce hypersensitivity.
      Our data also demonstrate that additional damage to the spinal cord upon
      placement of a graft further compromises behavioral recovery for locomotor and
      postural function. Additional therapeutic interventions will be necessary to
      provide greater levels of recovery after chronic injuries.

PMID- 14637086
TI  - A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy.
AB  - A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome
      consistent with frontotemporal dementia with extensive tau pathology; however,
      neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl
      insoluble tau extracted from affected brain tissue consisted almost exclusively
      of four-repeat isoforms. Consistent with these findings, in vitro biochemical
      assays demonstrated that the I260V mutation causes a selective increase in tau
      aggregation and a decrease in tau-induced microtubule assembly with four-repeat
      isoforms only. The contrasting pathology and biochemical effects of this mutation
      suggest a different disease mechanism from the other exon 9 mutations and
      demonstrates the critical role for the first microtubule-binding domain in tau
      promoted microtubule assembly and the pathogenic aggregation of tau.

PMID- 14637087
TI  - Directed nerve outgrowth is enhanced by engineered glial substrates.
AB  - In the present study, the influence of astrocyte alignment on the direction and
      length of regenerating neurites was examined in vitro. Astrocytes were
      experimentally manipulated by different approaches to create longitudinally
      aligned monolayers. When cultured on the aligned monolayers, dorsal root ganglion
      neurites grew parallel to the long axis of the aligned astrocytes and were
      significantly longer than controls. Engineered monolayers expressed linear arrays
      of fibronectin, laminin, neural cell adhesion molecule, and chondroitin sulfate
      proteoglycan that were organized parallel to one another, suggesting that a
      particular spatial arrangement of these molecules on the astrocyte surface may be
      necessary to direct nerve regeneration in vivo. In contrast, no bias in
      directional outgrowth was observed for neurites growing on unorganized
      monolayers. The results suggest that altering the organization of astrocytes and
      their scar-associated matrix at the lesion site may be used to influence the
      direction and the length of adjacent regenerating axons in the damaged brain and
      spinal cord.

PMID- 14637088
TI  - Human alpha2-macroglobulin: genotype-phenotype relation.
AB  - A pentanucleotide deletion polymorphism in the gene of alpha2-macrolgobulin
      (alpha2-M) is suggested to be associated with late-onset Alzheimer's disease
      (AD), though controversial results have been reported. The underlying assumption
      is that the intronic pentanucleotide deletion may affect the biological function
      and quantity of the inhibitor and thus contribute to the AD pathology. In the
      present study we have analyzed the distribution of the deletion polymorphism
      within a group of 227 healthy Caucasians. In parallel studies, we determined the
      plasma concentrations of total and transformed alpha2-M. A strong correlation of
      the total concentration of alpha2-M with age was ascertained (r(s) = -0.54, P <
      0.001). However, no significant correlation between age and the genotypes (P =
      0.68) was detected, and no statistically significant effect of the genotype on
      the concentrations of total and transformed alpha2-M was found (P = 0.49 and
      0.96, respectively). A significant correlation was observed between total and
      transformed alpha2-M in the genotype groups Ins/Ins (r(s) = 0.56, P < 0.001) and
      Ins/Del (r(s) = 0.35, P < 0.004). Furthermore, in the entire data set, a
      significantly elevated concentration of total alpha2-M was found in females as
      compared to males (P = 0.003). There was a slight but nonsignificant difference
      in the genotype distributions between males and females (P = 0.14). To test the
      proposed existence of genotype-specific alterations of functional properties of
      alpha2-M, we isolated alpha2-M from the plasma of carriers with different genetic
      background and analyzed the alpha2-M subunit structure as well as the binding of
      the inhibitor to growth factors/cytokines, to amyloid-beta and to the receptor.
      The experiments failed to reveal any genotype-specific functional alterations of
      the alpha2-M. The absence of abnormalities in alpha2-M mRNA and protein suggests
      that the alpha2-M deletion polymorphism is probably not associated with
      functional deficiencies important in AD pathology. However, it can be speculated
      that the observed general age-related alpha2-M deficiency may lead to accelerated
      accumulation of amyloid-beta, which might be relevant to AD pathology.

PMID- 14637089
TI  - Regulation of peripheral inflammation by spinal adenosine: role of somatic
      afferent fibers.
AB  - Spinal administration of adenosine inhibits neutrophil accumulation in skin. The
      neural pathways mediating this action are unknown. We investigated individually
      the roles of capsaicin sensitive primary afferent fibers, sympathetic efferent
      fibers, and dorsal roots in this regulation. One week after implantation of
      intrathecal (IT) catheters into rats, the adenosine receptor agonist
      cyclohexyladenosine (CHA) or vehicle was injected intrathecally. Inflammatory
      skin lesions were induced by intradermal carrageenan. Three hours later, skin was
      harvested and assayed for neutrophils by measuring myeloperoxidase (MPO)
      activity. Intrathecal CHA (5 microg/kg) decreased neutrophil infiltration into
      skin lesions. Nociceptive peptides were largely depleted from central terminals
      of primary afferents by IT capsaicin pretreatment. This depletion had no effect
      on either basal neutrophil infiltration or CHA-mediated modulation. Sympathetic
      fibers were largely destroyed by systemic 6-hydoxydopamine (6-OHDA) pretreatment;
      sympathectomy did not affect basal neutrophil infiltration or block its
      suppression by IT CHA. Thus, spinal adenosine effects on skin neutrophil
      trafficking appear to be independent of sympathetic nerves and primary afferent
      peptides, although incomplete lesions by chemical pretreatments may have
      confounded our results. Sensory fibers were interrupted by prior unilateral
      dorsal rhizotomies. This procedure had no effect on neutrophil accumulation in
      control rats. However, rhizotomy blocked the CHA effect, with MPO levels 45 +/-
      18% greater in denervated than control skin in IT CHA-treated animals (P < 0.05).
      It is clear that the spinal adenosine effect requires intact somatic
      connectivity. Information on pain and inflammation in the periphery is
      transmitted to the nervous system, where increased spinal adenosine levels can
      suppress peripheral inflammation.

PMID- 14637090
TI  - Interaction between serotonergic and noradrenergic axons during axonal
      regeneration.
AB  - The present experiments focused on the morphological interaction between
      serotonergic (5-HT) and noradrenergic (NA) axons during regeneration following
      partial axonal denervation in the cerebral cortex in adult rats. The denervation
      paradigm used employed two neurotoxins, one for 5-HT and one for NA axons,
      infused together at one cortical site while a single neurotoxin to either 5-HT or
      NA was infused at the symmetrical cortical site in the other hemisphere. This
      treatment enabled us to assess the role of 5-HT or NA axons in the regeneration
      of the other monoaminergic axon. 5-HT axon regeneration became apparent as early
      as 28 days after the toxin injection, whereas the regeneration of NA axons was
      not evident even at 60 days after the toxin injection. Since NA axons revealed
      marked regeneration in the cortical site with denervation of 5-HT axons, intact 5
      HT axons may be inhibitory on the regeneration of NA axons. In contrast, since
      the regeneration of 5-HT axons was suppressed in the absence of NA axons, NA
      axons appear to exert a facilitatory effect on 5-HT axon regeneration. These
      results suggest that the role of 5-HT axons in the regeneration of NA axons is
      opposite to that of NA axons in the regeneration of 5-HT axons. In addition, the
      regeneration of 5-HT axons occurred much faster than that of NA axons in response
      to axonal damage. The differential roles of 5-HT and NA axons in axonal
      regeneration may play a role in a variety of physiological functions related to
      these monoamines and possibly in the pathophysiology of clinical depression.

PMID- 14637091
TI  - Kainic acid-induced convulsions cause prolonged changes in the chondroitin
      sulfate proteoglycans neurocan and phosphacan in the limbic structures.
AB  - Systemic administration of kainic acid induces repeated convulsive seizures (KA
      convulsions) that result in neuropathological changes similar to temporal lobe
      epilepsy and the appearance of spontaneous recurrent seizures (SRS). The
      appearance of SRS is considered a result of the remodeling of neuronal networks
      following neuronal degeneration. We investigated the changes in chondroitin
      sulfate proteoglycans (CSPGs) in the limbic structures after KA convulsions in
      the rat using monoclonal antibodies 1G2, which recognizes full-length neurocan
      and the C-terminal half of neurocan, neurocan C, and 6B4, which recognize
      phosphacan and protein tyrosine phosphatase zeta. After KA convulsions, full
      length neurocan appeared by 24 h and reached a peak by 48 to 72 h, whereas
      phosphacan decreased within 24 h in the hippocampus. In immunohistochemistry,
      neurocan increased in the limbic structures coincident with the appearance of
      reactive astrocytes. Phosphacan decreased coincident with pyramidal cell loss in
      the hippocampus, and the number of phosphacan-positive perineuronal nets around
      parvalbumin neurons decreased, whereas parvalbumin neurons were relatively
      conserved. In contrast, phosphacan increased in the entorhinal and piriform
      cortices in correlation with the severity of neuronal loss. Both neurocan and
      phosphacan recovered to the control level by 8 weeks after KA convulsions in some
      rats, but the changes in neurocan and phosphacan described above still persisted
      in more than half the rats. The results indicate that KA convulsions induce
      prolonged changes in neurocan and phosphacan similar to those in the developing
      rat brain and suggest a role of these CSPGs in the remodeling of neuronal
      networks related to the establishment or enhancement of epileptogenesis.

PMID- 14637092
TI  - Suppression of hippocampal neurogenesis is associated with developmental stage,
      number of perinatal seizure episodes, and glucocorticosteroid level.
AB  - Seizures increase dentate granule cell proliferation in adult rats but decrease
      proliferation in young pups. The particular period and number of perinatal
      seizures required to cause newborn granule cell suppression in development are
      unknown. Therefore, we examined cell proliferation with bromodeoxyuridine (BrdU)
      immunohistochemistry during the peak of neurogenesis (e.g., P6 and P9) and at
      later postnatal ages (e.g., P13, P20, or P30) following single and multiple
      episodes of perinatal status epilepticus induced by kainate (KA). Because an
      inverse relationship exists between glucocorticosteroids (CORT) levels and
      granule cell proliferation, plasma CORT levels and electroencephalographic (EEG)
      activity were simultaneously monitored to elucidate underlying mechanisms that
      inhibit cell proliferation. In control animals, the number of BrdU-labeled cells
      increased then declined with maturation. After 1x KA or 2x KA administered on P6
      and P9, the numbers of BrdU-labeled cells were not different from age-matched
      controls. However, rat pups with 3x KA (on P6, P9, and P13) had marked
      suppression of BrdU-labeled cells 48-72 h after the last seizure (43 +/- 6.5% of
      control). Cell proliferation was also significantly inhibited on P20 after 2x KA
      (to 56 +/- 6.9%) or 3x KA (to 54 +/- 7.9%) and on P30 with 3x KA (to 74.5 +/-
      8.2% of age-matched controls). Cell death was not apparent as chromatin stains
      showed increased basophilia of only inner cells lining the granule cell layers,
      in the absence of eosinophilia, argyrophilia, or terminal deoxynucleotidyl dUTP
      nick endlabeling (TUNEL) labeling at times examined. In P13 pups with 3x KA,
      electron microscopy revealed an increased number of immature granule cells and
      putative stem cells with irregular shape, condensed cytoplasm, and electron dense
      nuclei, and they were also BrdU positive. The EEG showed no relationship between
      neurogenesis and duration of high-synchronous ictal activity. However, endocrine
      studies showed a correlation with BrdU number and age, sustained increases in
      circulating CORT levels following 1x KA on P6 (0.7 +/- 0.1 to 2.40 +/- 0.86
      microg/dl), and cumulative increases that exceeded 10 microg/dl at 4-8 h after 3x
      KA on P13 or P20. In conclusion, a history of only one or two perinatal
      seizure(s) can suppress neurogenesis if a second or third seizure recurs after a
      critical developmental period associated with a marked surge in CORT. During the
      first 2 weeks of postnatal life sustained increases in postictal circulating CORT
      levels but not duration or intensity of ictal activity has long-term consequences
      on neurogenesis. The occurrence of an increased proportion of immature granule
      cells and putative stem cells with irregular morphology in the absence of
      neurodegeneration suggests that progenitors may not differentiate properly and
      remain in an immature state.

PMID- 14637093
TI  - Age-dependent synuclein pathology following traumatic brain injury in mice.
AB  - Synucleins (Syn), a family of synaptic proteins, includes alpha-Syn, which plays
      a pivotal role in Parkinson's disease and related neurodegenerative diseases
      (synucleinopathies) by forming distinct brain pathologies (Lewy bodies and
      neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor
      for Parkinson's disease, we examined the effects of TBI in the young and aged
      mouse brain on alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed
      that brains from sham-injured young and aged mice had normal alpha- and beta-Syn
      immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with
      little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a
      transient increase of alpha- and beta-Syn IR in the neuropil as well as an
      induction of gamma-Syn IR in subcortical axons. This was associated with strong
      labeling of striatal axon bundles by antibodies to altered or nitrated epitopes
      in alpha-Syn as well as by antibodies to inducible nitric oxide synthase.
      However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered
      Syn IR was not seen in young mice subjected to TBI nor in alpha-Syn knockout mice
      while Western blots confirmed that TBI induced transient alterations of alpha-Syn
      in the mouse brains. This model of age-dependent TBI-induced transient
      alterations in alpha-Syn provides an opportunity to examine possible links
      between TBI and mechanisms of disease in synucleinopathies.

PMID- 14637094
TI  - Thyroid hormone reduces the loss of axotomized sensory neurons in dorsal root
      ganglia after sciatic nerve transection in adult rat.
AB  - We have shown that a local administration of thyroid hormones (T3) at the level
      of transected rat sciatic nerve induced a significant increase in the number of
      regenerated axons. To address the question of whether local administration of T3
      rescues the axotomized sensory neurons from death, in the present study we
      estimated the total number of surviving neurons per dorsal root ganglion (DRG) in
      three experimental group animals. Forty-five days following rat sciatic nerve
      transection, the lumbar (L4 and L5) DRG were removed from PBS-control, T3-treated
      as well as from unoperated rats, and serial sections (1 microm) were cut. The
      physical dissector method was used to estimate the total number of sensory
      neurons in the DRGs. Our results revealed that in PBS-control rats transection of
      sciatic nerve leads to a significant (P < 0.001) decrease in the mean number of
      sensory neurons (8743.8 +/- 748.6) compared with the number of neurons in
      nontransected ganglion (mean 13,293.7 +/- 1368.4). However, administration of T3
      immediately after sciatic nerve transection rescues a great number of axotomized
      neurons so that their mean neuron number (12,045.8 +/- 929.8) is not
      significantly different from the mean number of neurons in the nontransected
      ganglion. In addition, the volume of ganglia showed a similar tendency. These
      results suggest that T3 rescues a high number of axotomized sensory neurons from
      death and allows these cells to grow new axons. We believe that the relative
      preservation of neurons is important in considering future therapeutic approaches
      of human peripheral nerve lesion and sensory neuropathy.

PMID- 14637095
TI  - Olfactory ensheathing cells induce less host astrocyte response and chondroitin
      sulphate proteoglycan expression than Schwann cells following transplantation
      into adult CNS white matter.
AB  - Both Schwann cells and olfactory ensheathing cells (OECs) create an environment
      favorable to axon regeneration when transplanted into the damaged CNS. However,
      transplanted cells can also exert an effect on the host tissue that will
      influence the extent to which regenerating axons can grow beyond the transplanted
      area and reenter the host environment. In this study equivalent numbers of Lac-Z
      labeled Schwann cells and OECs have been separately transplanted into normal
      white matter of adult rat spinal cord and the host astrocyte response to each
      compared. Schwann cell transplantation resulted in a greater area of increased
      glial fibrillary acidic protein (GFAP) expression compared to that associated
      with OEC transplantation. This was accompanied by a greater increase in the
      expression of axon growth inhibitory chrondroitin sulfate proteoglycans (CSPGs)
      following Schwann cell transplantation compared to OEC transplantation. However,
      no differences were detected in the increased expression of the specific CSPG
      neurocan following transplantation of the two cell types. These results mirror
      differences in the interactions between astrocytes and either Schwann cells or
      OECs observed in tissue culture models and reveal one aspect of the complex
      biology of creating regeneration-promoting environments by cell transplantation
      where transplanted OECs have favorable properties compared to transplanted
      Schwann cells.

PMID- 14637096
TI  - Time sequence of maturation of dystrophic neurites associated with Abeta deposits
      in APP/PS1 transgenic mice.
AB  - Several novel transgenic mouse models expressing different mutant APPs in
      combination with mutant PS1 have been developed. These models have been analyzed
      to investigate the formation and progressive alterations of dystrophic neurites
      (DNs) in relation to Abeta deposits. In the most aggressive model, Abeta deposits
      appear as early as 2.5 months of age. Maturation of DNs was qualitatively quite
      similar among models and in some respect reminiscent of human AD pathology. From
      the onset of deposition, most if not all Abeta deposits were decorated with a
      high number of APP-, ubiquitin-, and MnSOD-immunoreactive DNs. Phosphorylated Tau
      DNs, however, appeared at a much slower rate and were more restricted.
      Mitochondrial dysfunction markers were observed in DNs: the frequency and the
      density per deposit of DNs accumulating cytochrome c, cytochrome oxidase 1, and
      Bax progressively increased with age. Later, the burden of reactive DNs was
      reduced around large compact/mature deposits. In addition, the previously
      described phenomenon of early intraneuronal Abeta accumulation in our models was
      associated with altered expression of APP protein as well as oxidative and
      mitochondrial stress markers occasionally in individual neurons. The present
      study demonstrates that oxidative and mitochondrial stress factors are present at
      several phases of Abeta pathology progression, confirming the neuronal
      dysfunction in APP transgenic mice.

PMID- 14637097
TI  - Peripheral nerve ischemia: apolipoprotein E deficiency results in impaired
      functional recovery and reduction of associated intraneural angiogenic response.
AB  - Apolipoprotein E-knockout (apoE KO) mice have peripheral sensory nerve defects,
      reduced and delayed response to noxious thermal stimuli, abnormal morphology of
      unmyelinated fibers, and impaired blood-nerve and blood-brain barriers. In this
      study, we show that, compared to wild-type mice, peripheral nerves of apoE KO
      mice have impaired ability to respond to ischemia, as demonstrated by measurement
      of motor and sensory conduction velocity. In addition, mice lacking apoE exhibit
      a deficit of reinnervation of ischemic epidermis, evaluated by immunofluorescent
      staining for the pan-neuronal marker PGP 9.5. Also regional nerve blood flow,
      measured by laser Doppler, and intraneural angiogenesis after ischemia are
      significantly compromised in apoE-deficient mice. Finally, upregulation of the
      angiogenic cytokine vascular endothelial growth factor (VEGF), which
      physiologically occurs after ischemia in the peripheral nerve of wild-type mice,
      is severely impaired in apoE KO mice. Among the several neural defects that have
      already been described in mice lacking apoE, this is the first demonstration that
      functional recovery to ischemia is impaired in the peripheral nerves of these
      animals. This deficit is mirrored by the inability of upregulating VEGF and
      mounting an appropriate intraneural angiogenic response following injury. These
      findings provide new evidence of possible interdependent relationships between
      VEGF, angiogenesis, and nerve function and regeneration and may provide new
      important information on the role of apoE in the nervous system.

PMID- 14637098
TI  - Motor training effects on recovery of function after striatal lesions and
      striatal grafts.
AB  - Environment, training, and experience can influence plasticity and recovery of
      function after brain damage. However, it is less well known whether, and how,
      such factors influence the growth, integration, and functional recovery provided
      by neural grafts placed within the brain. To explore this process, rats were
      pretrained on the skilled staircase test, then lesioned unilaterally in the
      lateral dorsal striatum with quinolinic acid. Half of the animals were given
      suspension grafts prepared from E15 whole ganglionic eminence implanted into the
      lesioned striatum. For the following 5 months, half of the animals in each group
      were trained daily in a bilateral manual dexterity task. Then, 23 weeks after
      surgery, all animals were retested on the staircase test. The grafts promoted
      recovery in the reaching task, irrespective of the additional dexterity training,
      and within the trained group recovery was proportional to the volume of the
      striatal-like tissue in the graft, suggesting that training influenced the
      pattern of graft-induced functional recovery. The additional training also
      benefited the rats with lesions alone, raising their performance close to level
      of the grafted groups. In separate tests of rotation, the grafts reduced drug
      induced ipsilateral turning in response to both amphetamine and apomorphine, an
      effect that was greater in the grafted rats given extra training. The results
      suggest that both nonspecific motor training and cell transplantation can
      contribute to recovery of lost function in tests of spontaneous and skilled
      lateralized motor function after striatal damage, and that these two factors
      interact in a task-specific manner.

PMID- 14637099
TI  - A2A antagonist prevents dopamine agonist-induced motor complications in animal
      models of Parkinson's disease.
AB  - Adenosine A(2A) receptors, abundantly expressed on striatal medium spiny neurons,
      appear to activate signaling cascades implicated in the regulation of coexpressed
      ionotropic glutamatergic receptors. To evaluate the contribution of adenosinergic
      mechanisms to the pathogenesis of the response alterations induced by
      dopaminergic treatment, we studied the ability of the selective adenosine A(2A)
      receptor antagonist KW-6002 to prevent as well as palliate these syndromes in
      rodent and primate models of Parkinson's disease. In rats, KW-6002 reversed the
      shortened motor response produced by chronic levodopa treatment while reducing
      levodopa-induced hyperphosphorylation at S845 residues on AMPA receptor GluR1
      subunits. In primates, KW-6002 evidenced modest antiparkinsonian activity when
      given alone. Once-daily coadministration of KW-6002 with apomorphine prevented
      the development of dyskinesias, which appeared in control animals 7-10 days after
      initiating apomorphine treatment. Animals initially given apomorphine plus KW
      6002 for 3 weeks did not begin to manifest apomorphine-induced dyskinesias until
      10-12 days after discontinuing the A(2A) antagonist. These results suggest that
      KW-6002 can attenuate the induction as well as the expression of motor response
      alterations to chronic dopaminergic stimulation in parkinsonian animals, possibly
      by blocking A(2A) receptor-stimulated signaling pathways. Our findings strengthen
      the rationale for developing A(2A) antagonists as an early treatment strategy for
      Parkinson's disease.

PMID- 14637100
TI  - Controlled release of nerve growth factor enhances sciatic nerve regeneration.
AB  - Based on previous studies demonstrating the potential of growth factors to
      enhance peripheral nerve regeneration, we developed a novel growth factor
      delivery system to provide sustained delivery of nerve growth factor (NGF). This
      delivery system uses heparin to immobilize NGF and slow its diffusion from a
      fibrin matrix. This system has been previously shown to enhance neurite outgrowth
      in vitro, and in this study, we evaluated the ability of this delivery system to
      enhance nerve regeneration through conduits. We tested the effect of controlled
      NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve
      defect. The heparin-containing delivery system was studied in combination with
      three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with
      positive controls (isografts) and negative controls (fibrin alone, NGF alone, and
      empty conduits). Nerves were harvested at 6 weeks postoperatively for
      histomorphometric analysis. Axonal regeneration in the delivery system groups
      revealed a marked dose-dependent effect. The total number of nerve fibers at both
      the mid-conduit level and in the distal nerve showed no statistical difference
      for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The
      results of this study demonstrate that the incorporation of a novel delivery
      system providing controlled release of growth factors enhances peripheral nerve
      regeneration and represents a significant contribution toward enhancing nerve
      regeneration across short nerve gaps.

PMID- 14637101
TI  - The effects of chronic L-DOPA therapy on pharmacodynamic parameters in a rat
      model of motor response fluctuations.
AB  - Chronic L-3,4-dihydroxyphenylalanine (L-DOPA) therapy in Parkinson's disease (PD)
      is complicated by motor response fluctuations and dyskinesia. The relative
      contributions of disease severity and chronic L-DOPA therapy to the development
      of motor fluctuation are not well defined clinically. Experimental studies have
      been limited partly because models for the antiparkinsonian effects on akinesia
      have not been employed. Therefore, we employed a model of akinesia using forepaw
      adjusting steps that have been well characterized to reflect the effect of
      lesions and the antiparkinsonian effect of dopaminergic drugs and transplants. We
      administered L-DOPA (12.5 mg/kg) intermittently for 4 weeks to rats with severe
      nigrostriatal lesions produced by injecting 6-hydroxydopamine into the medial
      forebrain bundle. The peak magnitude responses to L-DOPA increased after
      treatment compared to the pretreatment baseline. The latency to peak response to
      L-DOPA became shorter and reversed after the discontinuation of treatment. The
      duration of response showed minor changes. The pattern of changes in response to
      apomorphine was similar to that of L-DOPA except that the peak magnitude did not
      increase despite chronic L-DOPA treatment. The changes in D1 and D2 receptor
      binding did not correlate with behavioral changes. In summary, long-term
      intermittent L-DOPA treatment resulted in priming of antiparkinsonian effects on
      improving akinesia in a rat model of severe PD. These observed changes do not
      mirror all aspects of motor response fluctuations in advanced PD patients and
      suggest differential contributions of dopaminergic treatment and lesion severity
      to motor complication patterns.

PMID- 14637102
TI  - Differences in cytokine gene expression profile between acute and secondary
      injury in adult rat spinal cord.
AB  - It is likely that the environment within the injured spinal cord influences the
      capacity of fetal spinal cord transplants to support axonal growth. We have
      recently demonstrated that fetal spinal cord transplants and neurotrophin
      administration support axonal regeneration after spinal cord transection, and
      that the distance and amount of axonal growth is greater when these treatments
      are delayed by several weeks after injury. In this study, we sought to determine
      whether differences in inflammatory mediators exist between the acutely injured
      spinal cord and the spinal cord after a second injury and re-section, which could
      provide a more favorable environment for the axonal re-growth. The results of
      this study show a more rapid induction of transforming growth factor (TGF) beta1
      mRNA expression in the re-injured spinal cord than the acutely injured spinal
      cord and an attenuation of proinflammatory cytokine mRNA expression. Furthermore,
      there was a rapid recruitment of activated microglia/macrophages in the
      degenerating white matter rostral and caudal to the injury but fewer within the
      lesion site itself. These findings suggest that the augmentation of TGFbeta-1
      gene expression and the attenuation of pro-inflammatory cytokine gene expression
      combined with an altered distribution of activated microglia/macrophages in the
      re-injured spinal cord might create a more favorable milieu for transplants and
      axonal regrowth as compared to the acutely injured spinal cord.

PMID- 14637103
TI  - Neurons derived from embryonic stem (ES) cells resemble normal neurons in their
      vulnerability to excitotoxic death.
AB  - We determined whether embryonic stem (ES) cells could provide a model system for
      examining neuronal death mediated by glutamate receptors. Although limited
      evidence indicates that normal neurons can be derived from mouse ES cells, there
      have been no studies examining pathophysiological responses in mouse ES cell
      systems. Mouse ES cells, induced down a neural lineage by retinoic acid (RA),
      were found to have enhanced long-term survival when plated onto a layer of
      cultured mouse cortical glial cells. In these conditions, the ES cells
      differentiated into neural cells that appeared normal morphologically and
      displayed normal features of immunoreactivity when tested for neuron-specific
      elements. Varying the culture medium generated cultures of mixed neuronal/glial
      cells or enriched in oligodendrocytes. These cultures were viable for at least
      four weeks. Real-time PCR analysis of N-methyl-D-aspartate (NMDA) receptor
      subunits revealed an appropriate age-in-vitro dependent pattern of expression.
      Neurons derived from ES cells were vulnerable to death induced by a 24-h exposure
      to the selective glutamate receptor agonists NMDA, kainate, and alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). This vulnerability to agonist
      induced death increased with age in vitro, and related closely to expression of
      receptor subunits, as it does in cultured primary neurons. Experiments with
      selective receptor antagonists showed that glutamate receptors mediated the NMDA-
      and kainate-induced death. Neuronal differentiated ES cells therefore exhibited
      an excitotoxic response resembling that displayed by central nervous system (CNS)
      neurons. Thus, ES cells, which are very amenable to genetic manipulation, provide
      a valid system for studying glutamate receptor-mediated toxicity at the molecular
      level.

PMID- 14637104
TI  - Zinc released from metallothionein-iii may contribute to hippocampal CA1 and
      thalamic neuronal death following acute brain injury.
AB  - Vesicular zinc was initially considered the sole source of toxic intraneuronal
      zinc accumulation in response to acute brain injury, but recent evidence suggests
      that additional sources also exist. Because metallothioneins (MTs) can bind and
      release zinc, we examined the possibility that the brain-specific form, MT-III,
      is such a zinc source. After kainate-induced seizures, cytoplasmic zinc
      accumulation and neuronal death in the hippocampal CA1 region and the thalamus
      were substantially lower in Mt3-null mice than in wild-type mice. Furthermore,
      compared with zinc transporter 3 (Znt3)-null mice, Znt3/Mt3 double-null mice
      exhibited further reductions in neuronal death in CA1 following kainate-induced
      seizures. Similar reductions in zinc accumulation and neuronal death in
      hippocampal CA1 and the dentate gyrus in Mt3-null mice were observed in a sodium
      nitroprusside model of acute brain injury. In contrast to CA1, more neuronal
      death occurred after kainate-induced seizures in CA3 of Mt3-null mice. These
      results suggest that intracellular zinc release from MT-III may contribute
      substantially to zinc-mediated neuronal death in certain brain areas, including
      the hippocampal CA1 region and the thalamus.

PMID- 14637105
TI  - Combinatorial code of growth factors and neuropeptides define neuroendocrine
      differentiation in PC12 cells.
AB  - Adrenal chromaffin cells constitute one of the first cell types to have been
      defined as a neuroendocrine cell type. Since they produce dopamine, these cells
      have been proposed for the treatment of neuronal deficits in human Parkinson's
      disease. However, the factors involved in the development of chromaffin cells are
      still poorly understood. Based on recent insights from stem cell research, we
      decided to study the role of extracellular matrices, growth factors and
      neuropeptides on the neuroendocrine differentiation in a serum-free medium of
      PC12 cells. Employing immunohistochemistry, quantitative PCR and HPLC analysis,
      neuroendocrine differentiation was determined by evaluating neurite outgrowth,
      catecholamine biosynthesis and release as well as neuropeptide and vesicular
      protein mRNA expression. The combination of bFGF, NGF and PACAP could prevent the
      inhibition of neurite process development induced by dexamethasone in PC12 cells
      cultured on ECM. Whereas glucocorticoids were essential in the regulation of
      enzymes of catecholamine biosynthesis and metabolism, growth factors and PACAP
      were more efficient in inducing neuropeptide and chromogranin B expression as
      well as release of dopamine and 3-methoxytyramine. Therefore, in addition to
      glucocorticoids, chromaffin cells need a gradient of matrix, growth factors, and
      neuropeptides to develop the full functional phenotype of a neuroendocrine cell.

PMID- 14637106
TI  - PARP cleavage, DNA fragmentation, and pyknosis during excitotoxin-induced
      neuronal death.
AB  - Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear enzyme activated by DNA breaks
      and serves a role in DNA repair through the formation of polymers
      (poly(ADP)ribosylation) at sites of DNA damage. PARP-1 is activated by DNA damage
      in neurons of the hippocampus and cerebral cortex following excessive exposure to
      glutamate receptor agonists such as NMDA or kainic acid. In addition, recent
      studies suggest that degradation of PARP-1 occurs in cells that undergo apoptotic
      versus nonapoptotic forms of cell death. To investigate this process further, we
      examined the spatiotemporal aspects of excitotoxic injury in the rodent visual
      cortex by making focal intracerebral injections of kainic acid. These injections
      resulted in DNA damage, PARP-1 activation, and neuronal cell death over a 5-day
      period. Rapid neuronal cell injury assessed by Fluoro-Jade staining appeared
      within hours, but increased TUNEL staining occurred only after 24 h. A dramatic
      increase in caspase-3 activity, as well as an increase in the number of neurons
      containing active caspase-3, peaked 2 days after injury. Last, increased PARP-1
      immunoreactivity and PARP-1 cleavage reached peak levels 2 to 3 days after
      delivering the excitotoxin. These findings suggest that increased caspase-3
      activity may regulate the degradation of PARP-1 in subsets of cortical neurons
      during excitotoxic cell death.

PMID- 14637107
TI  - Direct evidence of primary afferent sprouting in distant segments following
      spinal cord injury in the rat: colocalization of GAP-43 and CGRP.
AB  - Mechanical and thermal allodynia develops after spinal cord injury in three areas
      relative to the lesion: below level, at level, and above level. The present study
      tests colocalization of CGRP, associated with nociceptive neurons, with growth
      associated protein (GAP-43), expressed in growing neurites, to test for neurite
      sprouting as a mechanism for reorganization of pain pathways at the level of the
      lesion and distant segments. Male Sprague-Dawley rats were divided into three
      groups: sham control (N = 10), hemisected at T13 and sacrificed at 3 days (N = 5)
      and at 30 days (N = 5) following surgery, the spinal cord tissue was prepared for
      standard fluorescent immunocytochemistry using mouse monoclonal anti-GAP-43
      (1:200) and/or rabbit polyclonal anti-CGRP (1:200), density of immunoreaction
      product (IR) was quantified using the Bioquant software and values from the
      hemisected group were compared to similar regions from the sham control. We
      report significant increases at C8 and L5, in CGRP-IR in lamina III compared to
      control tissue (P < 0.05). We report significant bilateral increases in GAP-43-IR
      at C8, T13, and L5 segments in lamina I through IV, at 3 days post hemisection,
      compared to control tissue (P < 0.05), some of which is colocalized with alpha
      CGRP. The increased area and density of GAP-43-IR is consistent with neurite
      sprouting, and the colocalization with alpha-CGRP indicates that some of the
      sprouting neurites are nociceptive primary afferents. These data are consistent
      with endogenous regenerative neurite growth mechanisms that occur near and
      several segments from a spinal lesion, that provide one of many substrates for
      the development and maintenance of the dysfunctional state of allodynia after
      spinal cord injury.

PMID- 14637108
TI  - Enhancement of neuronal protection from oxidative stress by glutamic acid
      decarboxylase delivery with a defective herpes simplex virus vector.
AB  - We have developed defective herpes simplex virus 1 (HSV-1) vectors, based on
      amplicon plasmids with a replication-deficient mutant, as helper for the transfer
      of the glutamic acid decarboxylase (GAD67) or beta-galactosidase (beta-gal) gene
      as control directed by HCMV promoter into neuronal-like cells (PC12) and primary
      neurons. GAD67 protein was detected immunochemically, while GAD67 activity in
      virus-producing and nonproducing cell lines was detected enzymatically or by GABA
      release. Infection with GAD67-expressing amplicon vectors enhanced the resistance
      of PC12 cells to H(2)O(2). This protection was related to increased energy
      metabolism, as shown by MTT reduction and ATP level, and involved the GABA shunt,
      as shown by the reduction in ATP level seen in the presence of gamma-vinyl GABA
      (GVG), a specific GABA transaminase inhibitor. Level of glutathione (GSH), which
      requires ATP for its synthesis, was increased by the GAD67 transgene. The
      activity of glucose-6-phosphate dehydrogenase involved in the maintenance of the
      NADPH that can be used for the regeneration of the GSH pool, was increased by
      infection with amplicon vectors. Thus, replication-deficient HSV-1 and the GAD67
      transgene have complementary neuroprotective effects and infection with GAD67
      expressing amplicon vectors was able to protect nondifferentiated cortical
      neurons from glutamate toxicity mediated by oxidative stress. Such defective
      GAD67-expressing HSV-1, as neurotropic vector, should be helpful in
      neurodegenerative diseases implicating alterations of energy metabolism and
      oxidative stress in neuronal cells expressing GABA transaminase.

PMID- 14637109
TI  - Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson
      agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo
      against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to
      ropinirole.
AB  - The novel naphtoxazine derivative and preferential D(3) vs D(2) receptor agonist,
      S32504, restores perturbed motor function in rodent and primate models of
      antiparkinsonian activity with a potency superior to those of two further,
      preferential D(3) receptor agonists, pramipexole and ropinirole. However,
      potential neuroprotective properties of S32054 have not, to date, been evaluated.
      Herein, employing several measures of cellular integrity, we demonstrate that
      S32504 robustly, concentration-dependently and completely protects terminally
      differentiated SH-SY5Y cells against 1-methyl-4-phenylpyridinium (MPP+)-induced
      cell death in vitro. Further, S32504 was substantially more potent than
      pramipexole and ropinirole, the latter of which was neurotoxic at high
      concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5
      mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against
      MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the
      substantia nigra pars compacta and ventral tegmental area. A high dose of
      ropinirole (2.5 mg/kg) provided some protection but statistical significance was
      not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded
      protection against the MPTP-induced loss of DA fibers in the striatum, as
      measured by TH-IR and dopamine transporter immunoreactive fiber counts. In
      conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly
      protects dopaminergic neurones against the neurotoxic effects of MPP(+) and MPTP
      in in vitro and in vivo models, respectively. The underlying mechanisms and
      therapeutic pertinence of these actions will be of interest to further evaluate
      in view of its potent actions in behavioral models of antiparkinson activity.

PMID- 14637110
TI  - Human midsized neurofilament subunit induces motor neuron disease in transgenic
      mice.
AB  - Aberrant accumulation of neurofilaments is a feature of human motor neuron
      diseases. Experimentally motor neuron disease can be induced in transgenic mice
      by overexpressing the mouse neurofilament light subunit (NF-L), the human heavy
      subunit (NF-H), or mouse peripherin. Here we describe that mice harboring a
      bacterial artificial chromosome (BAC) transgene containing the human midsized
      neurofilament subunit (NF-M) gene develop a progressive hind limb paralysis
      associated with neurofilamentous accumulations in ventral horn motor neurons and
      axonal loss in ventral motor roots. Biochemical studies revealed that all three
      mouse neurofilament subunits along with the human NF-M contributed to filament
      formation, although filaments contained less peripherin. In addition the
      endogenous mouse NF-M became less phosphorylated in the presence of the human
      protein and accumulated in the cell bodies of affected neurons even though
      phosphorylated human NF-M did not. Remaining motor axons contained an increased
      density of neurofilaments and morphometric studies showed that principally small
      myelinated axons were lost in the transgenic animals. Removing half of the mouse
      NF-M by breeding the transgene onto the mouse NF-M heterozygous null background
      offered no protection against the development of disease, arguing that the effect
      is not simply due to elevation of total NF-M. Collectively these studies argue
      that the human and mouse NF-M proteins exhibit distinct biochemical properties
      and within mouse neurons are not interchangeable and that indeed the human
      protein may be toxic to some mouse neurons. These studies have implications for
      the use of human neurofilament transgenic mice as models of amyotrophic lateral
      sclerosis.

PMID- 14637111
TI  - Susceptibility of hippocampal neurons to mechanically induced injury.
AB  - Experimental models of traumatic cortical brain injury in rodents reveal that
      specific regions of the hippocampus (e.g., CA3 and hilar subfields) are severely
      injured despite their distance from the initial insult. Hippocampal neurons may
      be intrinsically more vulnerable to mechanical insult than cortical neurons due
      to increased NMDA receptor densities and lower energy capacities, as evidenced by
      increased susceptibility to ischemic insults. The selective vulnerability of
      hippocampal neurons was evaluated using an in vitro model of TBI in which either
      primary rat cortical or hippocampal neurons (E17) seeded onto silicone substrates
      were subjected to graded levels of mechanical stretch. Although cortical neurons
      exhibited significantly longer increases in stretch-induced membrane
      permeability, injury of hippocampal neurons resulted in larger increases in
      intracellular free calcium concentration [Ca(2+)](i) and cell death. [ATP](i)
      deficits due to stretch were apparent by 60 min after injury in cortical neurons
      but recovered by 24 h, whereas significant deficits in [ATP](i) were not observed
      in hippocampal neurons until 24 h after injury. MK801 pretreatment decreased the
      stretch-induced [Ca(2+)](i) transients in both hippocampal and cortical cultures,
      thereby negating the regional specificity. However, MK801 pretreatment did not
      improve hippocampal viability and paradoxically, significantly increased cell
      death among cortical neurons. As the hippocampus is the primary brain region
      responsible for the memory deficits and epileptic seizures associated with TBI,
      understanding why this region is selectively damaged could lead to the
      development of more accurate mechanical tolerances as well as effective
      pharmaceutical agents.

PMID- 14637112
TI  - P0 mRNA expression increases during gradual nerve elongation in adult rats.
AB  - Leg lengthening with nerve elongation is a common clinical treatment. We
      investigated morphological and molecular changes in peripheral nerves associated
      with femoral lengthening using animal models. Sciatic nerves of 13 week old male
      Wistar rats (n = 35) were elongated indirectly by leg lengthening for 14 days at
      1 mm/day. At 3, 7, 14, 21, and 35 days following initiation of elongation,
      sciatic nerves on the elongated side and contralateral (control) side were
      excised at the midpoint of the femur. Internodal length was increased by 17%.
      Light and electron microscopic observation of transverse sections at 14 days
      showed elongated nerves appearing similar to control nerves with no degenerating
      axons and normal myelin thickness. We next examined changes of mRNA expression of
      a major myelin glycoprotein, P0, in elongated nerves using a quantitative reverse
      transcription-polymerase chain reaction and in situ hybridization. P0 mRNA
      expression in elongated nerves was increased during the first 3 weeks, with
      expression reaching 160% of control nerve expression at 14 days. Results of in
      situ hybridization were confirmatory. We concluded that myelin synthesis occurred
      during gradual nerve elongation. In adulthood, Schwann cells retain ability to
      synthesize myelin in response to nerve stretching.

PMID- 14637113
TI  - SUMO-1 marks the nuclear inclusions in familial neuronal intranuclear inclusion
      disease.
AB  - Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative
      disorder characterized by progressive ataxia and neuronal nuclear inclusions
      (NIs), similar to the inclusions found in expanded CAG repeat diseases. NIID may
      be familial or sporadic. The cause of familial NIID is poorly understood, as no
      CAG expansion has been detected. We examined three cases, from two unrelated
      families, who had autosomal dominant NIID but normal CAG repeats in genes
      involved in polyglutamine neurodegenerative diseases. We found that NIs in all
      three cases were intensely immunopositive for SUMO-1, a protein which covalently
      conjugates to other proteins and targets them to the nuclear regions (nuclear
      bodies) responsible for nuclear proteasomal degradation. Electron microscopy
      demonstrated that SUMO-1 was located on the 10-nm fibrils of NIs. In cultured
      PC12 cells, we found that inhibition of proteasome function by specific
      inhibitors resulted in the appearance of SUMO-1-immunopositive nuclear
      inclusions. Our study suggests that recruitment of SUMO-1 modified proteins into
      insoluble nuclear inclusions and proteasomal dysfunction may be involved in the
      pathogenesis of NIs in familial NIID cases.

PMID- 14637114
TI  - Neurturin and persephin promote the survival of embryonic basal forebrain
      cholinergic neurons in vitro.
AB  - The GDNF family ligands (GFLs) are a group of neurotrophic factors that influence
      the development, survival, and maintenance of specific populations of neurons in
      the central and peripheral nervous systems. The cholinergic neurons of the basal
      forebrain provide cholinergic innervation to cortical structures and their
      integrity is vital to normal cognitive function. GDNF, the original member of the
      GFL family promotes the survival of developing basal forebrain cholinergic
      neurons in vitro. We have now found that neurturin (NRTN) and persephin (PSPN)
      also promote the survival of basal forebrain neurons including both cholinergic
      neurons and a population of non-cholinergic neurons with an efficacy comparable
      to NGF. We also demonstrate that developing and mature basal forebrain
      cholinergic neurons (BFCN) express GFL receptors. Ret, the signaling component of
      the GFL-receptor complex, is expressed in most adult rat BFCN. In addition, Ret
      and the GFL co-receptors GFRalpha1 and GFRalpha2 are expressed in developing
      cholinergic neurons in cultures of embryonic basal forebrain. Our results suggest
      that the GFLs may be effective as neuroprotective agents for BFCNs in vivo.

PMID- 14637115
TI  - Reducing inflammation decreases secondary degeneration and functional deficit
      after spinal cord injury.
AB  - Injury to the spinal cord is followed by degeneration, which leads to progressive
      tissue loss and usually cystic cavitation. Cellular and humoral immune responses
      have been implicated as mediators of secondary degeneration, and the expression
      of leukocyte chemoattractants has been shown to precede immune cell influx.
      However, the relationship between the increased expression of chemoattractants,
      the invasion of lymphocytes, and overall lesion evolution is poorly understood.
      Here, we show that the T-lymphocyte chemoattractant CXCL10 is upregulated after
      dorsal hemisection injury to the adult mammalian spinal cord of C57/BL6 mice, and
      that antibody neutralization of CXCL10 beginning 1 day prior to injury
      dramatically reduces the T-lymphocyte invasion that normally occurs after trauma.
      Notably, this treatment resulted in a significant reduction of secondary tissue
      loss and functional deficit. We conclude that CXCL10 plays a critical role in
      recruitment of T lymphocytes to sites of spinal cord injury, and that a reduction
      of T-lymphocyte recruitment significantly enhances tissue preservation and
      functional outcome.

PMID- 14637116
TI  - Loss of calretinin immunoreactive fibers in subcortical visual recipient
      structures of the RCS dystrophic rat.
AB  - The retinae of dystrophic Royal College of Surgeons (RCS) rats exhibit
      progressive photoreceptor degeneration accompanied by pathology of ganglion
      cells. To date, little work has examined the consequences of retinal degeneration
      for central visual structures in dystrophic rats. Here, we use
      immunohistochemistry for calretinin (CR) to label retinal afferents in the
      superior colliculus (SC), lateral geniculate nucleus, and olivary pretectal
      nucleus of RCS rats aged between 2 and 26 months of age. Early indications of
      fiber loss in the medial dystrophic SC were apparent between 9 and 13 months.
      Quantitative methods reveal a significant reduction in the level of CR
      immunoreactivity in visual layers of the medial dystrophic SC at 13 months (P <
      0.02). In dystrophic animals aged 19-26 months the loss of CR fibers in SC was
      dramatic, with well-defined patches of fiber degeneration predominating in medial
      aspects of the structure. This fiber degeneration in SC was accompanied by
      increased detection of cells immunoreactive for CR. In several animals, regions
      of fiber loss were also found to contain strongly parvalbumin-immunoreactive
      cells. Loss of CR fibers was also observed in the lateral geniculate nucleus and
      olivary pretectal nucleus. Patterns of fiber loss in the dystrophic SC compliment
      reports of ganglion cell degeneration in these animals and the response of
      collicular neurons to degeneration is discussed in terms of plasticity of the
      dystrophic visual system and properties of calcium binding proteins.

PMID- 14637117
TI  - Sex-related difference in collateral sprouting of nociceptive axons after
      peripheral nerve injury in the rat.
AB  - Possible sex-related differences in the extent of collateral sprouting of
      noninjured nociceptive axons after peripheral nerve injury were examined. In the
      first experiment, peroneal, tibial, and saphenous nerves were transected and
      ligated in female and male rats. Eight weeks after nerve injury, skin pinch tests
      revealed that the nociceptive area of the noninjured sural nerve in the instep
      skin expanded faster in females; the final result was a 30% larger increase in
      females than in males. In the second experiment, the end-to-side nerve
      anastomosis was used as a model for axon sprouting. In addition to the previous
      procedure, the end of an excised peroneal nerve segment was sutured to the side
      of the intact sural nerve. Eight weeks later, collateral sprouting of nociceptive
      axons into the anastomosed peroneal nerve segment was assessed by the nerve pinch
      test and axon counting. There was no significant difference with respect to the
      percentages of male and female rats with a positive nerve pinch test. The number
      of myelinated axons in the anastomosed nerve segment was significantly larger in
      female (456 +/- 217) than in male (202 +/- 150) rats, but the numbers of
      unmyelinated axons were not significantly different. In normal sural nerves, the
      numbers of either all myelinated axons or thin myelinated axons did not
      significantly differ between the two sexes. Therefore, the more extensive
      collateral axon sprouting observed in female than in male rats is probably due to
      the higher sprouting capacity of thin myelinated sensory axons in females.

PMID- 14637118
TI  - Lead exposure through gestation-only caused long-term learning/memory deficits in
      young adult offspring.
AB  - Numerous observations in clinical and preclinical studies indicate that the
      developing brain is particular sensitive to lead (Pb)'s pernicious effects.
      However, the effect of gestation-only Pb exposure on cognitive functions at
      maturation has not been studied. We investigated the potential effects of three
      levels of Pb exposure (low, middle, and high Pb: 0.03%, 0.09%, and 0.27% of lead
      acetate-containing diets) at the gestational period on the spatial memory of
      young adult offspring by Morris water maze spatial learning and fixed
      location/visible platform tasks. Our results revealed that three levels of Pb
      exposure significantly impaired memory retrieval in male offspring, but only
      female offspring at low levels of Pb exposure showed impairment of memory
      retrieval. These impairments were not due to the gross disturbances in motor
      performance and in vision because these animals performed the fixed
      location/visible platform task as well as controls, indicating that the specific
      aspects of spatial learning/memory were impaired. These results suggest that
      exposure to Pb during the gestational period is sufficient to cause long-term
      learning/memory deficits in young adult offspring.

PMID- 14637119
TI  - Effects of acetylcholinesterase and butyrylcholinesterase on cell survival,
      neurite outgrowth, and voltage-dependent calcium currents of embryonic ventral
      mesencephalic neurons.
AB  - The aim of this study was to investigate the effect of butyrylcholinesterase
      (BuChE) and acetylcholinesterase (AChE) on cell survival, neurite outgrowth and
      voltage-dependent calcium currents in developing rat ventral mesencephalic (VM)
      neurons. Both BuChE and AChE have been shown to promote neurite outgrowth in
      postnatnal preparations. However, the effect of these substances has never been
      investigated on rat embryonic VM cells, which are used in animal models of foetal
      transplantation as a treatment for Parkinson's disease. The effects of incubation
      with BuChE and tetrameric (G(4))- or monomeric (G(1))-AChE on cell survival and
      neurite outgrowth were characterised over a 7-day period on dopaminergic cells
      within embryonic VM cultures. The acute effects of these treatments on voltage
      dependent calcium currents from embryonic VM cells were then investigated using
      whole-cell voltage-clamp recordings. The chronic effect of modulating voltage
      dependent calcium channels was subsequently explored using the selective calcium
      channel antagonists omega-agatoxin IVA, omega-conotoxin GVIA, and nifedipine. The
      results presented here demonstrate firstly trophic effects of BuChE and G(4)- and
      G(1)-AChE upon dopaminergic neurite outgrowth, secondly that BuChE and G(4)- and
      G(1)-AChE have an inhibitory effect on voltage-dependent calcium currents, and
      finally that selective voltage-dependent calcium channel inhibitors also have
      trophic effects upon dopaminergic neurite outgrowth.

PMID- 14637120
TI  - Prevention of age-related spatial memory deficits in a transgenic mouse model of
      Alzheimer's disease by chronic Ginkgo biloba treatment.
AB  - Alzheimer's disease (AD) is characterized by cognitive decline and deposition of
      beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD
      model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein
      exhibits age-related cognitive deficits, Abeta plaque deposition, and oxidative
      damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich
      antioxidant, to antagonize the age-related behavioral impairment and
      neuropathology exhibited by Tg2576 mice. At 8 months of age, 16 female Tg2576 and
      15 female wild-type (wt) littermate mice were given ad lib access to tap water or
      Ginkgo biloba (70 mg/kg/day in water). After 6 months of treatment, all mice
      received Morris water maze training (4 trials/day for 10 days) to assess
      hippocampal dependent spatial learning. All mice received a 60-s probe test of
      spatial memory retention 24 h after the 40th trial. Untreated Tg2576 mice
      exhibited a spatial learning impairment, relative to wt mice, while Ginkgo biloba
      treated Tg2576 mice exhibited spatial memory retention comparable to wt during
      the probe test. Spatial learning was not different between Ginkgo biloba-treated
      and untreated wt mice. There were no group differences in learning to swim to a
      visible platform. Soluble Abeta and hippocampal Abeta plaque burden did not
      differ between the Tg2576 groups. Brain levels of protein carbonyls were
      paradoxically elevated in Ginkgo biloba-treated mice. These data indicate that
      chronic Ginkgo biloba treatment can block an age-dependent decline in spatial
      cognition without altering Abeta levels and without suppressing protein oxidation
      in a transgenic mouse model of AD.

PMID- 14637121
TI  - Neuroprotective actions of the ginseng extract G115 in two rodent models of
      Parkinson's disease.
AB  - The herbal remedy, ginseng, has recently been demonstrated to possess
      neurotrophic and neuroprotective properties, which may be useful in preventing
      various forms of neuronal cell loss including the nigrostriatal degeneration seen
      in Parkinson's disease (PD). In these studies, we examine the potential
      neuroprotective actions of the ginseng extract, G115, in two rodent models of PD.
      Animals received oral administration of G115 prior to and/or following exposure
      to the parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), in mice, or its toxic metabolite, 1-methyl-4
      phenylpyridinium (MPP(+)), in rats. Such treatment significantly and dramatically
      blocked tyrosine hydroxylase-positive cell loss in the substantia nigra and
      reduced the appearance of locomotor dysfunction. Thus, oral administration of
      ginseng appears to provide protection against neurotoxicity in rodent models of
      PD. Further examination of the neuroprotective actions of ginseng and its various
      elements may provide a potential means of slowing the progress of PD.

PMID- 14637122
TI  - The dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic
      neurodegeneration.
AB  - Many dopamine agonists used in the treatment of Parkinson's disease are suggested
      to be potentially neuroprotective. On the basis of its structure, the dopamine
      agonist lisuride may share this characteristic. In the current study discrete
      asymptomatic lesions were produced by the injection of iron-laden neuromelanin
      into the rat substantia nigra and the animals treated with lisuride to determine
      the protective potential of this substance. Two treatment regimes were utilised.
      In the neuroprotective protocol, animals were treated with 0.1 mg.kg(-1) lisuride
      twice daily 3 days prior to, and 7 days following, the iron lesion. In the
      neurorescue protocol, the animals received 0.1 mg.kg(-1) lisuride twice daily for
      1 week beginning on the fourth day post surgery. Eight weeks post surgery,
      tyrosine hydroxylase-positive neurons surrounding the injection site (33% of
      total nigral volume) were counted. Dopamine neuron number in iron-lesioned
      animals was reduced to 50% of that in vehicle-injected animals. The absence of
      motoric disturbances or a striatal dopamine deficit in these animals suggests a
      subclinical dopaminergic lesion. Dopamine neuron number in the quantified area in
      sham-injected animals receiving lisuride or iron-lesioned animals receiving
      lisuride in both the neuroprotection and neurorescue groups were not
      significantly reduced. These results suggest that lisuride can protect neurons
      against iron-induced cell death and might thus be neuroprotective in Parkinson's
      disease.

PMID- 14637124
TI  - Developmental characteristics of picrotoxin-induced convulsions in rats with
      genetic absence epilepsy.
AB  - Adult rats with genetic absence epilepsy (GAERS) were shown to be hyperresponsive
      to convulsions induced by picrotoxin compared to nonepileptic controls (NERs). In
      contrast, young GAERS aged 22-26 days were less responsive than NERs to
      picrotoxin-induced convulsions. Around 30 days of age, when spontaneous spike
      wave discharges develop in GAERS, the sensitivity of both strains did no longer
      differ. After 40 days of age, GAERS appeared definitely more prone than NERs to
      convulse in response to picrotoxin injection. A developmental imbalance in
      excitation/inhibition may parallel the occurrence of SWDs.

PMID- 14637123
TI  - Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides
      protection against 6-OHDA lesion in the common marmoset monkey (Callithrix
      jacchus).
AB  - Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a
      treatment for Parkinson's disease. Recombinant adeno-associated viral vectors
      expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of
      Parkinson's disease to promote functional regeneration after 6-OHDA lesions of
      the nigrostriatal system. The goal of the present study was to assess the
      anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey
      (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia
      nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle.
      Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV
      GDNF-treated monkeys survived, compared with 21% in the untreated monkeys. Fine
      dopaminergic fibres were observed microscopically in the injected striatum of
      some rAAV-GDNF-treated monkeys, suggesting that rAAV-GDNF treatment may have
      prevented, at least in part, the loss of dopaminergic innervation of the
      striatum. Protection of dopamine cells and striatal fibre innervation was
      associated with amelioration of the lesion-induced behavioural deficits. rAAV
      GDNF-treated monkeys showed partial or complete protection not only in the
      amphetamine and apomorphine rotation but also in head position and the
      parkinsonian disability rating scale. Therefore, our study provides evidence for
      the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a
      possible treatment for Parkinson's disease.

PMID- 14637125
TI  - 'I have a dream...'.cancer nursing leadership.

PMID- 14637126
TI  - Assessing fatigue and self-care strategies in patients receiving radiotherapy for
      non-small cell lung cancer.
AB  - Lung cancer represents a major public health problem worldwide (ISD 2000) with
      approximately 80% of patients presenting with locally advanced or metastatic
      disease. Treatment is essentially palliative; therefore, symptom management is
      important. This paper describes the findings from a prospective study of fatigue
      in newly diagnosed patients with non-small cell lung cancer. Fifty-three patients
      undergoing radical or high-dose palliative radiotherapy for Stage I, II and III
      disease were recruited to the study. Patients completed a structured health diary
      throughout radiotherapy and for up to 1 month post-treatment. Tape-recorded
      interviews were conducted with a sub-sample (n=11) to explore the nature of
      fatigue. Complete data sets were available on 46 patients. Consistent with
      current literature, the study findings demonstrated the progressive nature of
      this symptom throughout treatment; however, the levels of distress reported and
      interference with daily living were not found to be as overwhelming in this group
      of patients as the literature thus far suggests.

PMID- 14637127
TI  - Collaboration, user involvement and education: a systematic review of the
      literature and report of an educational initiative.
AB  - Collaboration is advocated widely through government policy as part of enormous
      change within the Health Service (Department of Health 1998, 2000b). Directives
      from policy regarding collaboration impact onto organizations, professions and
      individuals including users of the service. A literature review suggests that
      there would appear to be limited anecdotal, discursive or rigorous evidence
      available on collaboration at all levels including involving users. However,
      literature does demonstrate a mounting body of evidence that collaboration with
      users is being promoted as a way of working. This paper reviews the literature
      around collaboration and user involvement in the context of cancer care. Findings
      suggest that there is confusion of terminology around collaboration and user
      involvement. Benefits of and barriers to user involvement are identified and
      these are explored in the context of caring for the patient with cancer. An
      evaluation of a team-based educational initiative designed to help health-care
      professionals working within the cancer arena to explore ways to collaborate with
      users is presented. Findings suggest that education may be one way to develop
      collaboration between health-care professionals and service users.

PMID- 14637128
TI  - Developing nursing care guidelines for children with Hodgkin's disease.
AB  - Oncology patients are generally treated on therapeutic research protocols that
      detail medical treatment. Nursing care is not clearly defined in these protocols;
      therefore, the need to develop a set of guidelines specifically for nursing care
      was identified. To further enhance the specialized care that our pediatric
      oncology patients receive, we developed nursing care guidelines to accompany
      specific protocols. One of our most highly accruing protocols is designed to
      treat patients diagnosed with Hodgkin's disease. In an effort to increase
      understanding of this clinical trial, decrease potential for errors, and improve
      overall quality of patient care, nursing care guidelines were created. To develop
      the nursing care guidelines, nurses created a seven-step process: (1) studied the
      therapeutic protocol, established ongoing interactions with the principal
      investigator (brainstorming), reviewed benchmarking, (2) created the first draft
      of the guidelines, compared the formatting of this particular set of guidelines
      with those previously developed at this setting (drafting), (3) field tested
      guidelines, (4) revised the guidelines and subjected them to additional field
      testing, (5) examined the guidelines for implications related to teaching tools,
      (6) implemented the guidelines through in-services, and (7) developed an
      evaluation plan with pre- and post-tests that indicated improved disease and
      treatment knowledge among participating nurses. Potential contributions from
      implementing nursing care guidelines that parallel therapeutic protocols include
      more accurate and complete research data collection and a more defined role for
      nurses in the protocol development process. The guidelines also offer a useful,
      detailed resource to deliver complex protocol-directed care.

PMID- 14637130
TI  - Selected nursing abstracts from ECCO 12, Copenhagen, 21-25 September 2003.

PMID- 14637129
TI  - The psycho-social effects of chemotherapy toxicity--a patient perspective: short
      report.

PMID- 14637132
TI  - Molecular and catalytic properties of three rat leukotriene C(4) synthase
      homologs.
AB  - The committed step in the biosynthesis of cysteinyl-leukotrienes is catalyzed by
      leukotriene C(4) synthase as well as microsomal glutathione S-transferase (MGST)
      type 2 and type 3, which belong to a family of membrane-associated proteins in
      eicosanoid and glutathione metabolism (MAPEG). We cloned and characterized these
      three enzymes from the rat to allow a side-by-side comparison of structural and
      catalytic properties. The proteins are 79.6-86.7% identical to the human
      orthologs. Rat MGST3 fails to convert leukotriene A(4) into leukotriene C(4),
      which in turn challenges the proposed catalytic role of a conserved Arg and Tyr
      residue for the leukotriene C(4) synthase reaction. Comparative inhibitor studies
      of all three enzymes, using MK-886 and cysteinyl-leukotrienes, indicate that
      their catalytic centers originate from structurally related and overlapping
      active sites. Hence, it seems feasible to design enzyme inhibitors, which
      simultaneously target several members of this protein family to yield compounds
      with increased anti-inflammatory action.

PMID- 14637133
TI  - Regulatory sequence elements of mouse GLUT4 gene expression in adipose tissues.
AB  - Ablation of GLUT4 in adipose tissues results in whole body insulin resistance and
      high-fat feeding down-regulates GLUT4 mRNA in white adipose tissues. Previous
      studies demonstrated that adipose tissue specific element(s) (ASE) of the murine
      GLUT4 gene is located between -551 and -442 relative to transcription start site
      and that high-fat responsive element(s) (HFRE) for down-regulation of the GLUT4
      gene is located between bases -1001 and -442. To further characterize these
      regulatory elements, the regulation of GLUT4 minigenes containing -701, -551, and
      -506 bp of 5(')-flanking region was studied in transgenic mice. GLUT4 minigene
      mRNA from -506 transgenic mice did not express in adipose tissues, indicating
      that ASE located within 45 bp is located between bases -551 and -506. An 80-kDa
      of nuclear DNA binding protein was found to bind to a -TCCTCGTGGGAAGCG- element
      located between bases -551 and -537. High-fat diet feeding down-regulated GLUT4
      minigene mRNA in -701 transgenic mice, but not in -551 transgenic mice,
      indicating that HFRE is located within 150 bp between bases -701 and -551 of the
      GLUT4 gene and is distinct from ASE.

PMID- 14637134
TI  - Lactic acid bacteria as prime candidates for codon optimization.
AB  - In species having a strong correlation of expressivity and codon bias it has been
      shown that heterologous expression can be optimized by changing codons of the
      introduced gene towards the set of codons that the host organism naturally uses
      in its highly expressed genes. Even though two lactic acid bacteria are fully
      sequenced, there are no reports on attempts of codon optimization in the
      literature. In this report it is demonstrated that codons used in highly
      expressed genes tend to differ from the codons in lowly expressed genes, and that
      there is a strong correlation of codon bias and empirical expressivity (codon
      adaptation index) in Lactococcus lactis and Lactobacillus plantarum. This
      strongly suggests that codon optimization strategies could be applied to
      expression systems with lactic acid bacteria as producer strains. A good example
      of a candidate for codon optimization is the mouse interleukin-2 gene, which in
      its natural form has an extremely low codon adaptation index for expression in
      Lc. lactis.

PMID- 14637135
TI  - Direct conversion of ferrous myeloperoxidase to compound II by hydrogen peroxide:
      an anaerobic stopped-flow study.
AB  - Myeloperoxidase (MPO) is one of the essential components of the antimicrobial
      systems of polymorphonuclear neutrophils. It is unique in having a globin-like
      standard reduction potential of the ferric/ferrous couple. Here, it is shown that
      ferrous MPO heterolytically cleaves hydrogen peroxide forming water and oxyferryl
      MPO (compound II). The two-electron oxidation reaction follows second-order
      kinetics with the apparent bimolecular rate constant being (6.8+/-0.6)x10(4)M(
      1)s(-1) at pH 7.0. After depletion of (micromolar) H(2)O(2) compound II slowly
      decays to ferric MPO, whereas upon addition of millimolar H(2)O(2) to ferrous
      MPO, compound III (oxyperoxidase) is formed in a sequence of two reactions
      involving compound II formation and its direct reaction with H(2)O(2), which also
      follows second-order kinetics [(78+/-2)M(-1)s(-1) at pH 7.0]. It is discussed how
      these reactions contribute to the interconversion of compound II and compound III
      and could explain the catalase activity of MPO.

PMID- 14637136
TI  - Modulation of hematology changes by polymorphism of glutathione S-transferase M1
      and T1.
AB  - Workers in the petroleum distribution trades experience relatively low-level
      exposures to gasoline vapors whose consequences have not been fully elucidated.
      The purpose of this study was to investigate changes in the hematological
      parameters among filling station workers who were occupationally exposed to
      gasoline. The target group for the study consisted of 41 workers from eight
      filling stations of Shiraz (south of Iran). The control group consisted of 27
      healthy subjects matched for age and sex from general population. The complete
      blood count analysis was done in one laboratory. Using PCR-based method, the
      genotypes of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) were determined.
      Workers were divided into three exposure groups according to employment history:
      duration less than 1 year, 1-5 years, and more than 5 years. Comparison was
      performed using Kruskal-Wallis test. In the individuals with the presence of both
      GSTT1 and GSTM1 functional alleles, comparison between four exposure groups
      revealed no significant difference for studied hematological variables. There
      were statistically significant differences between study groups, with only one
      functional allele, either GSTT1 or GSTM1, for relative number of lymphocytes
      (chi(2)=9.147, df=3, P=0.027) and neutrophils (chi(2)=9.951, df=3, and P=0.019),
      and absolute number of lymphocytes (chi(2)=9.135, df=3, and P=0.028), and RBC
      (chi(2)=10.586, df=3, and P=0.014). These findings could indicate the possible
      protective effect of concurrent presence of GSTM1 and GSTT1 enzymes on the
      hematopoietic system of filling station workers.

PMID- 14637137
TI  - Pyrroloquinoline-quinone synthesized in Escherichia coli by pyrroloquinoline
      quinone synthase of Deinococcus radiodurans plays a role beyond mineral phosphate
      solubilization.
AB  - Deinococcus radiodurans, an extremely radioresistant bacterium, synthesizes
      coenzyme pyrroloquinoline-quinone (PQQ) but exhibits a negative phenotype for
      mineral phosphate solubilization. Gene for the putative PQQ synthesizing protein
      was PCR amplified and cloned from Deinococcus, sequenced, and expressed in
      Escherichia coli, under an inducible E. coli promoter. The transgenic E. coli
      expressed PQQ synthase protein of 42kDa and complemented the mineral phosphate
      solubilization phenotype of E. coli, suggesting the synthesis of an active
      protein. The cells expressing high levels of this protein showed increased
      protection against photodynamically produced reactive oxygen species. The effect
      could be attributed to the upregulation of antioxidant enzymes such as catalase
      and superoxide dismutase by PQQ in transgenic E. coli through an unknown
      mechanism. The study elucidates a hitherto unknown possible function of PQQ in
      bacteria.

PMID- 14637138
TI  - A new human peptide deformylase inhibitable by actinonin.
AB  - Peptide deformylases (PDFs) have been investigated as potential specific targets
      for antibiotics, but the possible existence of a functional human PDF (HsPDF)
      presents a potential hurdle to the design of specific drugs. We have expression
      cloned a HsPDF that has deformylase activity, although it is a slower and
      catalytically less active enzyme than bacterial or plant PDFs. A cobalt
      substituted form of HsPDF (but not nickel or zinc) is active, and the enzyme
      appears to be active at a pH between 6.0 and 7.2, a temperature range of 25-50
      degrees C, and in a low KCl ionic strength buffer. Actinonin inhibits HsPDF
      activity with an IC50 of 43 nM and kills Daudi and HL60 human cancer cell lines
      with an LC50 of 5.3 and 8.8 microM, respectively. The inhibition of HsPDF may
      provide an explanation for the mechanism by which actinonin is cytotoxic against
      various human tumor cell lines.

PMID- 14637139
TI  - HPLC and LC-MS studies of hydroxylation of phenylalanine as an assay for hydroxyl
      radicals generated from Udenfriend's reagent.
AB  - An HPLC assay method and an LC-MS method were used to study the Udenfriend
      reaction and its variations by using phenylalanine as the hydroxylation
      substrate. The results indicate that (1). citric acid can replace EDTA as the
      promoter for the production of hydroxyl radicals in the Undenfriend reaction,
      albeit in a somewhat less efficient way, (2). dihydroxylation of the
      hydroxylation substrate, phenylalanine, readily occurs with the Udenfriend
      systems (with either EDTA or citric acid), and (3). a novel oxidative degradation
      pathway may exist for o-tyrosine. It is cautioned that dihydroxylation needs to
      be accounted for when interpreting hydroxylation results in HPLC-based HO(z.rad;)
      assay systems with phenylalanine as the substrate.

PMID- 14637140
TI  - Identification and physical organization of the gene cluster involved in the
      biosynthesis of Burkholderia cepacia complex exopolysaccharide.
AB  - Bacteria belonging to the Burkholderia cepacia complex (BCC) are important
      opportunistic pathogens in patients with cystic fibrosis (CF). Since
      approximately 80% of the CF isolates examined produce exopolysaccharide (EPS), it
      was hypothesized that this EPS may play a role in the colonization and
      persistence of these bacteria in the CF lung. The present study describes the
      identification and physical organization of the EPS biosynthetic gene cluster.
      This bce gene cluster was identified following the isolation of three EPS
      defective mutants from the highly mucoid CF isolate IST408, belonging to BCC
      genomovar I, based on random plasposon insertion mutagenesis and comparison of
      the nucleotide sequence of the interrupted genes with the available genome of
      Burkholderia cenocepacia J2315. This 16.2 kb cluster includes 12 genes and is
      located on chromosome 2. Database searches for homologous proteins and secondary
      structure analysis for the deduced Bce amino acid sequences revealed genes
      predicted to encode enzymes required for the formation of nucleotide sugar
      precursors, glycosyltransferases involved in the repeat-unit assembly, and other
      proteins involved in polymerization and export of bacterial surface
      polysaccharides.

PMID- 14637141
TI  - Inhibition of human salivary alpha-amylase by glucopyranosylidene-spiro
      thiohydantoin.
AB  - This study is the first report on the effectiveness and specificity of
      glucopyranosylidene-spiro-thiohydantoin (G-TH) inhibitor on the 2-chloro-4
      nitrophenyl-4-O-beta-D-galactopyranosyl-maltoside (GalG(2)CNP) hydrolysis
      catalysed by human salivary alpha-amylase (HSA). The inhibition of hydrolysis is
      a mixed-noncompetitive type. In any case, only one molecule of inhibitor binds to
      HSA. Since our substrate and inhibitor are small molecules the long enough active
      site facilitates accommodating both of them simultaneously. However, the product
      formation can be excluded from enzyme-substrate-inhibitor complex (ESI) since
      Dixon plots are linear. Kinetic constants calculated from secondary plots and
      nonlinear regression are almost entirely equal, confirming the fidelity of the
      suggested model. Kinetic constants (K(1i)=7.3mM, L(1i)=2.84 mM) show that G-TH is
      not such a potent inhibitor of HSA as acarbose and indicate higher stability for
      ESI than for enzyme-inhibitor complex.

PMID- 14637142
TI  - Crystal structure of nitrile hydratase from a thermophilic Bacillus smithii.
AB  - The crystal structure of the nitrile hydratase (NHase) from Bacillus smithii SC
      J05-1 was determined. Our analysis of the structure shows that some residues that
      seem to be responsible for substrate recognition are different from those of
      other NHases. In particular, the Phe52 in the beta subunit of NHase from B.
      smithii covers the metal center partially like a small lid and narrows the active
      site cleft. It is well known that the NHase from B. smithii especially prefers
      aliphatic nitriles for its substrate rather than aromatic ones, and we can now
      infer that the Phe52 residue may play a key role in the substrate specificity for
      this enzyme. This finding leads us to suggest that substitution of these residues
      may alter the substrate specificity of the enzyme.

PMID- 14637143
TI  - The association of the exon 4 variations of Tim-1 gene with allergic diseases in
      a Korean population.
AB  - The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is
      identified to be expressed on T cells. A member of Tim family, TIM-1, is
      considered as a membrane protein that is associated with the development of Th2
      biased immune responses and may be selectively expressed on Th2 cells. In the
      present study, we analyzed the association of allele and genotype frequencies
      between asthma or atopy patients and the controls without asthma and atopy using
      large sample size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene.
      Although the allele frequency of 5509_5511delCAA variation in asthma was not
      significantly different (P=0.085), the genotype of 5509_5511delCAA variation in
      asthma was significantly associated with the susceptibility to asthma (P=0.037).
      The genotype and allele frequencies of 5383_5397del variation in atopic
      dermatitis were significantly different from those in the non-asthmatic and non
      atopic controls (P=0.005 and P=0.002, respectively). Our results strongly suggest
      that the 5383_5397del variation site of Tim-1 exon 4 might be associated with
      atopic dermatitis susceptibility.

PMID- 14637144
TI  - Quantitative study of HIV-1 Tat peptide and TAR RNA interaction inhibited by
      poly(allylamine hydrochloride).
AB  - The interaction of poly(allylamine hydrochloride) (PAH) with TAR RNA has been
      studied by quartz crystal microbalance (QCM) cooperating with capillary
      electrophoresis (CE). Experimental results showed that PAH had high affinity for
      TAR RNA. In particular, PAH could disrupt the interaction of Tat peptide with TAR
      RNA, which is critical for HIV-1 virus replication. The approaches described here
      indicate that they are powerful for studying the binding processes of Tat peptide
      TAR RNA and drug-TAR RNA, having great significance for the design of new drug.

PMID- 14637145
TI  - Hydrogen peroxide increases a 55-kDa tyrosinase concomitantly with induction of
      p53-dependent p21 waf1 expression and a greater Bax/Bcl-2 ratio in pigmented
      melanoma.
AB  - Differentiated melanocytic cells produce melanin, through several redox reactions
      including tyrosinase-catalyzed DOPA oxidation to DOPA quinone. We now developed a
      method based on DOPA oxidase in-gel detection and Sypro Ruby fluorometric
      normalization to investigate induction of specific DOPA oxidase isoforms in
      response to hydrogen peroxide-mediated stress, and to ask whether this is
      associated with p53-dependent adaptive responses. This report shows that hydrogen
      peroxide leads to comparable induction of 60 and 55 kDa DOPA oxidases in poorly
      pigmented B16 melanoma, in contrast to sole induction of a major 55 kDa DOPA
      oxidase in their highly pigmented counterparts. In the latter cells, this
      response also increases p53 concomitant with joint induction of p53-activated
      proteins like the cell-cycle inhibitor p21WAF1 and pro-apoptotic bax, with no
      comparable effect on expression of anti-apoptotic bcl-2. Together, these data
      suggest that response to hydrogen peroxide involves p53-mediated growth
      restrictive signaling and unequal induction of specific DOPA oxidases in
      melanocytic cells with unequal basal pigmentation.

PMID- 14637146
TI  - LMW-PTP associates and dephosphorylates STAT5 interacting with its C-terminal
      domain.
AB  - Hematopoietic cells, particularly megakaryoblastic ones, display a high level of
      low M(r) phosphotyrosine protein phosphatase (LMW-PTP) expression; nevertheless,
      the role of this PTP in such cellular lineages has been scarcely investigated.
      Here, we demonstrate that LMW-PTP is able to associate and dephosphorylate signal
      transducer and activator of transcription-5 (STAT5) in DAMI megakaryocytic cells.
      Numerous researchers repeatedly hypothesized the association of a regulatory
      phosphotyrosine protein phosphatase with STAT5 C-terminus, but such
      phosphotyrosine protein phosphatase remained unknown. We show evidence indicating
      that the association of STAT5 and LMW-PTP does not exclusively involve the
      phosphatase active site and phosphotyrosine residue of STAT5, and we individuate
      an essential region of interaction at STAT5 C-terminus, coinciding with the
      previously hypothesized PTP-associating domain.

PMID- 14637147
TI  - Effects of aging and ischemia on adenosine receptor transcription in mouse
      myocardium.
AB  - The well-documented age-related change in ischemic tolerance may result from
      impaired adenosine-mediated cardioprotection. Additionally, ischemia itself may
      potentially modify adenosine signalling, contributing to the post-ischemic
      phenotype. This study investigates age- and ischemia-dependent changes in
      adenosine receptor transcript levels (Adora) for the A(1), A(2A), A(2B), and A(3)
      receptor subtypes in mouse myocardium. Hearts from young (2-4 months) and
      moderately aged (16-18 months) mice were subjected to 20-min ischemia and 45-min
      reperfusion. Ischemic tolerance was impaired in aged hearts, which recovered less
      than 30% ventricular pressure development (compared with approximately 70% in
      young hearts), and lost 2-fold higher levels of lactate dehydrogenase during
      reperfusion (reflecting cellular disruption). Real-time PCR analyses revealed an
      age-related decline in Adora3 levels and induction of Adora2B. Curiously, this
      effect was mimicked by ischemia, which acutely reduced Adora3 levels and induced
      Adora2B in young (but not old) hearts. In contrast, in aged hearts ischemia
      selectively reduced levels of Adora1 transcript ( approximately 2-fold) without
      altering transcript levels for the other receptors. These results demonstrate
      selective modulation of cardioprotective adenosine receptor transcription by both
      aging and ischemia. Reduced A(3) adenosine receptor transcription may contribute
      to impaired ischemic tolerance in aged hearts, whereas changes in Adora
      transcription induced by ischemia may impact on the post-ischemic phenotype at
      later time points.

PMID- 14637148
TI  - Toluene monooxygenase from the fungus Cladosporium sphaerospermum.
AB  - Assimilation of toluene by Cladosporium sphaerospermum is initially catalyzed by
      toluene monooxygenase (TOMO). TOMO activity was induced by adding toluene to a
      glucose-pregrown culture of C. sphaerospermum. The corresponding microsomal
      enzyme needed NADPH and O(2) to oxidize toluene and glycerol, EDTA, DTT, and PMSF
      for stabilization. TOMO activity was maximal at 35 degrees C and pH 7.5 and was
      inhibited by carbon monoxide, Metyrapone, and cytochrome c. TOMO preferred as
      substrates also other aromatic hydrocarbons with a short aliphatic side chain.
      Its reduced carbon monoxide difference spectrum showed a maximum at 451 nm. A
      substrate-induced Type I spectrum was observed on addition of toluene. These
      results indicated that TOMO is a cytochrome P450. TOMO and its corresponding
      reductase were eventually purified by a simultaneous purification revealing
      apparent molecular masses of 58 and 78 kDa, respectively.

PMID- 14637149
TI  - Negative regulation of p21 by beta-catenin/TCF signaling: a novel mechanism by
      which cell adhesion molecules regulate cell proliferation.
AB  - Cell proliferation is regulated in part by cell-cell interactions mediated by
      cadherin and connexin. Here we present evidence that these two molecules act
      synergistically to suppress HEK293 cell proliferation by prolonging the G2/M
      phase. This event was accompanied by expression of p21, a potent Cdc2 kinase
      inhibitor. Not surprisingly, there was a concomitant decline in Cdc2 kinase
      activity. beta-Catenin/TCF signaling, which was downregulated by overexpression
      of N-cadherin, was found to inhibit transactivation of p21 gene expression. The
      effect of N-cadherin on cell proliferation and p21 expression was augmented by co
      expression of connexin-43. Moreover, the magnitude of the connexin's effect was
      dependent on its ability to mediate intercellular communication. We conclude,
      therefore, that two major components of cell-cell interaction synergistically
      regulate cell cycle progression in HEK293 cells by regulating p21 expression in a
      beta-catenin/TCF-dependent manner.

PMID- 14637150
TI  - Transforming growth factor-beta1 stimulated protein kinase B serine-473 and focal
      adhesion kinase tyrosine phosphorylation dependent on cell adhesion in human
      hepatocellular carcinoma SMMC-7721 cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent growth inhibitor and
      apoptosis inducer for most normal cells. However, tumor cells are commonly
      nevertheless sensitive to the tumor-suppressing effects of TGF-beta1. In this
      paper, we focus on the effects of TGF-beta1 on two important anti-apoptotic
      protein kinases, protein kinase B (PKB), and focal adhesion kinase (FAK), in SMMC
      7721 cells. We found that PKB-Ser-473 phosphorylation was apparently up-regulated
      by TGF-beta1. In the meantime, PKB-Thr-308 phosphorylation was slightly up
      regulated by TGF-beta1. TGF-beta1 could also enhance FAK-Tyr phosphorylation. We
      observed that integrin-linked kinase (ILK) was also up-regulated by TGF-beta1 in
      good accordance with PKB-Ser-473 phosphorylation. We first found that TGF-beta1
      could stimulate PKB-Ser-473 phosphorylation possibly via up-regulating ILK
      expression. Furthermore, we also failed to detect PKB-Ser-473 and FAK-Tyr
      phosphorylation with various concentrations of TGF-beta1 treatment when cells
      were kept in suspension. The above results indicate that PKB-Ser-473 and FAK-Tyr
      phosphorylation stimulated by TGF-beta1 are both dependent on cell adhesion.

PMID- 14637152
TI  - On the structural significance of the linkage region constituents of N
      glycoproteins: an X-ray crystallographic investigation using models and analogs.
AB  - The linkage region constituents, namely, 2-acetamido-2-deoxy-beta-D-glucopyranose
      and asparagine are conserved in the N-glycoproteins of all the eukaryotes. The
      present work is aimed at understanding the reasons for the occurrence of GlcNAc
      and Asn as the linkage region constituents. A total of six sugar amides have been
      designed as models and analogs of the linkage region and their crystal structures
      have been solved. This is the first report on the X-ray crystallographic
      investigation of the effect of systematic changes in the linkage sugar as well as
      its aglycon moiety on the N-glycosidic torsion, psi(N) (O5-C1-N1-C1(')). This
      also forms the first report on the crystal structure of a model of L-RhabetaAsn,
      a variant linkage found in the surface layer glycoprotein of Bacillus
      stearothermophillus. Among the models and analogs examined, the acetamido
      derivatives of Man and Xyl, the linkage sugars of O-glycoproteins, show a psi(N)
      value of -114.5 degrees and -121.2 degrees, respectively, deviating maximum from
      the value of -89.8 degrees reported for the model compound GlcNAcbetaNHAc. The L
      Rha and Gal derivatives also show noticeable deviations. The psi(N) values, -89.5
      degrees and -91.0 degrees, of the propionamide derivatives of Glc and GlcNAc
      (analogs of GlcbetaGln and GlcNAcbetaGln, respectively) agree well with those (
      93.8 degrees and -89.8 degrees ) reported for their corresponding acetamide
      derivatives suggesting Gln could serve as well as Asn as the linkage region amino
      acid. However, the rotational freedom about the additional C-C bond would lead to
      altered rigidity of the linkage region. An analysis of packing reveals that the
      molecular assembly of these compounds is driven by different infinite and finite
      chains of hydrogen bonds. The double pillaring of hydrogen bonds involving the
      amide groups at C1 and C2 is seen as a unique packing feature characteristic of
      beta-1-N-acyl derivatives of GlcNAc. Based on the findings of the present study,
      it is speculated that the linkage region constituents of the eukaryotic N
      glycoproteins appear to fulfill three essential structural requirements:
      rigidity, planarity, and linearity and these are met by the trisaccharide core
      and Asn at the linkage region.

PMID- 14637151
TI  - Akt is an endogenous inhibitor toward tumor necrosis factor-related apoptosis
      inducing ligand-mediated apoptosis in rheumatoid synovial cells.
AB  - Akt is known to be activated in the rheumatoid synovial tissues. We examined here
      functional role of Akt during tumor necrosis factor-related apoptosis inducing
      ligand (TRAIL)-mediated apoptosis in rheumatoid synovial cells. Rheumatoid
      synovial cells in vitro were rapidly committed to apoptosis in response to TRAIL
      in mitochondria-dependent manner whereas Akt and extracellular signal-regulated
      kinase (ERK) were also phosphorylated. TRAIL-mediated apoptosis in synovial cells
      was significantly increased through inactivation of Akt by LY294002, however,
      that process was not so changed by adding ERK inhibitor, PD98059. Platelet
      derived growth factor (PDGF) clearly phosphorylated both Akt and ERK in synovial
      cells, and PDGF pretreatment markedly suppressed TRAIL-mediated synovial cell
      apoptosis. The use of not PD98059 but LY294002 abrogated PDGF-mediated inhibitory
      effect toward TRAIL-induced apoptosis in synovial cells. The above protective
      effect of Akt was confirmed by the use of short interfering RNA (siRNA)-directed
      inhibition of Akt. Our data suggest that Akt is an endogenous inhibitor during
      TRAIL-mediated synovial cell apoptotic pathway, which may explain that synovial
      cells in situ of the rheumatoid synovial tissues are resistant toward apoptotic
      cell death in spite of death receptor expression.

PMID- 14637153
TI  - Role of guanine nucleotide exchange factors for Rho family GTPases in the
      regulation of cell morphology and actin cytoskeleton in fission yeast.
AB  - Rho GTPases regulate fundamental processes including cell morphology and
      migration in various organisms. Guanine nucleotide exchange factor (GEF) has a
      crucial role in activating small GTPase by exchange GDP for GTP. In fission yeast
      Schizosaccharomyces pombe, six members of the Rho small GTPase family were
      identified and reported to be involved in cell morphology and polarized cell
      growth. We identified seven genes encoding Rho GEF domain from genome sequence
      and analyzed. Overexpressions of identified genes in cell lead to change of
      morphology, suggesting that all of them are involved in the regulation of cell
      morphology. Although all of null mutants were viable, two of seven null cells had
      morphology defects and five of seven displayed altered actin cytoskeleton
      arrangements. Most of the double mutants were viable and biochemical analysis
      revealed that each of GEFs bound to several small G proteins. These data suggest
      that identified Rho GEFs are involved in the regulation of cell morphology and
      share signals via small GTPase Rho family.

PMID- 14637154
TI  - GABA(B) receptor activation augments TASK-1 in MAH cells and mediates
      autoreceptor feedback during hypoxia.
AB  - Previously, we demonstrated an autoregulatory feedback loop in the rat carotid
      body (CB), involving presynaptic GABA(B) receptor-mediated activation of the
      background K(+) channel TASK-1. Here, we examined the effects of the selective
      GABA(B) receptor agonist baclofen on K(+) currents in immortalised
      adrenomedullary chromaffin (MAH) cells, which share the same sympathoadrenal
      lineage as CB type I cells. Under symmetrical K(+) conditions, 50 microM baclofen
      enhanced a K(+) current which was linear and reversed close to 0 mV. Under
      physiological K(+) conditions, baclofen enhanced outward K(+) current and caused
      membrane hyperpolarisation, effects inhibited by 100 nM CGP 55845. Current
      enhancement was virtually abolished in the presence of 300 microM Zn(2+), a
      selective inhibitor of TASK-1. When recording membrane potential from MAH cells
      in clusters, hypoxic depolarisation was augmented by 100 nM CGP 55845. These data
      demonstrate that GABA(B) receptors mediate autoreceptor feedback in the adrenal
      medulla presumably via TASK-1, demonstrating a common autoregulatory feedback
      pathway in neurosecretory, chemosensitive cells.

PMID- 14637155
TI  - Long form of cellular FLICE-inhibitory protein interacts with Daxx and prevents
      Fas-induced JNK activation.
AB  - Since Fas-induced apoptosis is major pathway to eliminate unwanted or
      uncontrolled cells, many types of human cancer cells develop tactful mechanisms
      to get resistance against the apoptosis. One of the resistant mechanisms in human
      cancer is overexpression of FLICE-inhibitory protein (c-FLIP), human homolog of
      viral protein v-FLIP. c-FLIP has multiple splice variants at transcriptional
      level or two isoforms at protein level, a long (c-FLIP(L)) and a short form of c
      FLIP (c-FLIP(S)). However, functional differences between these variants are not
      fully understood. In this study, we show that c-FLIP(L) but not c-FLIP(S)
      physically binds to Daxx through interaction between C-terminal domain of c
      FLIP(L) and Fas-binding domain of Daxx, an alternative Fas signaling adaptor. Fas
      induced cell death and JNK activation are sensitive to Fas stimulation in cell
      lines carrying undetectable level of c-FLIP(L). To support this, overexpression
      of c-FLIP(L) but not of c-FLIP(S) renders the cells resistant to Fas-induced cell
      death and to JNK activation. In signaling context, the interaction of c-FLIP(L)
      with Daxx is likely to inhibit JNK activation by preventing the normal
      interaction of Daxx and Fas, which is known to lead to apoptosis via JNK
      activation. This study implies that through this new mechanism, c-FLIP(L), acting
      at both FADD- and Daxx-mediated signaling pathways, may be involved in complete
      inhibition of Fas-induced cell death and may provide an answer to why c-FLIP(L)
      is more abundant and effective than c-FLIP(S).

PMID- 14637156
TI  - Deficit of CD38/cyclic ADP-ribose is differentially compensated in hearts by
      gender.
AB  - To elucidate whether myocardial CD38/cyclic ADP-ribose (cADPR) signaling plays a
      physiological role, we investigated the heart of CD38 knockout mice (CD38KO). In
      CD38KO, the myocardial cADPR content was reduced by 85% compared with wild-type
      mice (WT). Cardiac hypertrophy developed only in males. At 36 degrees C, none of
      the parameters for Ca(2+) transients and forces of the papillary muscles differed
      between WT and CD38KO. In contrast, at 27 degrees C, at which cADPR does not
      work, the peak [Ca(2+)](i) was increased and the decline in [Ca(2+)](i) was
      accelerated in CD38KO compared with WT. In CD38KO, the protein expression of SR
      Ca(2+) ATPase type2 (SERCA2) and the SERCA2-to-phospholamban ratio were increased
      compared with WT. The ryanodine receptor protein was increased only in female
      CD38KO compared with WT. These data suggest that the CD38/cADPR signaling plays
      an important role in intracellular Ca(2+) homeostasis in cardiac myocytes in
      vivo. Its deficiency was compensated differentially according to gender.

PMID- 14637157
TI  - Gender differences in the levels of bisphenol A metabolites in urine.
AB  - The metabolism of bisphenol A (BPA), a suspected endocrine disruptor, should be
      considered for monitoring human exposure to BPA, because the conjugation with
      beta-D-glucuronide and sulfate reduces the estrogenic activity. In this study,
      BPA levels in 30 healthy Koreans (men, N=15, 42.6+/-2.4 years; women, N=15,
      43.0+/-2.7 years) were analyzed from urine treated with/without beta
      glucuronidase and/or sulfatase by an RP-HPLC with fluorescence detection. The
      total BPA concentrations including free BPA and the urinary conjugates were
      similar in men and women (2.82+/-0.73 and 2.76+/-0.54 ng ml(-1), respectively),
      but gender differences were found in the levels of urinary BPA conjugates. Men
      had significantly higher levels of BPA-glucuronide (2.34+/-0.85 ng ml(-1)) than
      women (1.00+/-0.34 ng ml(-1)), whereas women had higher levels of BPA-sulfate
      (1.20+/-0.32 ng ml(-1)) than men (0.49+/-0.27 ng ml(-1)).

PMID- 14637158
TI  - Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and
      functional maturation of murine dendritic cells.
AB  - Acidic polysaccharides (PL) isolated from Phellinus linteus are known to
      stimulate the proliferation of T lymphocytes and humoral immune functions to act
      as a polyclonal activator of B cells, and to inhibit tumor growth and metastasis.
      However, little is known about their immunomodulating effects or the effects of
      its mechanisms on murine bone marrow (BM)-derived dendritic cells (DC). In this
      study, it profoundly increased CD80, CD86, MHC I, and MHC II expression in
      murine, GM-CSF and IL-4 stimulated, BM-derived myeloid DC. The ability of
      unstimulated DC to uptake dextran was higher than that of PL- or LPS-stimulated
      DC. We analyzed the concentration of IL-12 secreted by DC using flow cytometry
      and ELISA. Untreated DC secreted a low concentration of IL-12, while PL- or LPS
      stimulated DC secreted higher levels of IL-12 than untreated DC. There were no
      remarkable differences in the concentrations of IL-12 produced by PL- or LPS
      stimulated DC. However, polymyxin B (PB; an LPS inhibitor) effectively inhibited
      the surface molecules and IL-12 production induced by LPS, but had no effect on
      the PL in DC. PL-treated DC were much more potent antigen-presenting cells in
      allogeneic immune response than untreated DC. PL treatment not only formed
      morphologically mature DC but also induced predominant migration to lymphoid
      tissues. Moreover, the inhibitors of protein tyrosine kinase (PTK) or protein
      kinase C (PKC) significantly blocked the expression of surface molecules and IL
      12 production in PL-stimulated DC. Treatment of DC with PL directly induced PKC
      activity and phosphorylated PTK. Furthermore, CD11b and/or CD18 partially
      mediated PL-induced DC maturation.

PMID- 14637159
TI  - A putative coiled-coil domain of prohibitin is sufficient to repress E2F1
      mediated transcription and induce apoptosis.
AB  - Prohibitin is a potential tumor suppressor protein that can repress E2F-mediated
      transcription and arrest cell proliferation. We had shown previously that
      prohibitin could bind to the Rb protein as well as E2F and this binding was
      necessary to suppress cell proliferation. Here we show that the E2F1 binding
      domain of prohibitin has the potential to fold into a coiled-coil structure. This
      coiled-coil domain by itself could physically interact with E2F1 and block its
      transcriptional activity. Like full-length prohibitin, the coiled-coil domain
      also recruited histone deacetylase 1 to repress E2F1. The coiled-coil domain also
      exhibited growth suppressive properties and we observed a 64% reduction in colony
      numbers when transfected into T47D cells. Interestingly, a synthetic peptide
      corresponding to the coiled-coil domain induced apoptosis in four different human
      cell lines. It is possible that agents that can mimic this peptide would be of
      value in controlling proliferative disorders.

PMID- 14637160
TI  - A novel cold-adapted imidase from fish Oreochromis niloticus that catalyzes
      hydrolysis of maleimide.
AB  - In this paper we report the first comparative study of cold-adapted imidase (EC
      3.5.2.2) from the fish (Oreochromis niloticus) liver and its thermophilic
      counterparts taken from pig liver and Escherichia coli (overexpressed recombinant
      hydantoinase from Agrobacterium radiobacter NRRL B1). Approximately 6000-fold
      purification and a 40% yield of fish imidase activity were obtained through
      ammonium sulfate precipitation, octyl, chelating, DEAE, and hydroxyapatite
      chromatography. This cold-adapted imidase was characterized by a specific
      activity 10- to a 100-fold higher than those of its thermophilic counterparts
      below room temperature (25 degrees C or lower) conditions but less stable at
      elevated temperatures (40 degrees C or higher). A less organized helical
      structure (compared to those of pig liver and bacterial imidases) was observed by
      circular dichroism. Furthermore, maleimide was first identified as a novel
      substrate of all imidases examined, and confirmed by HPLC and NMR analysis. These
      results constituted a first study to discover a novel cold-adapted imidase with
      surprising high activity. These findings might be also helpful for industrial
      application of imidase.

PMID- 14637161
TI  - Novel heparan mimetics potently inhibit the scrapie prion protein and its
      endocytosis.
AB  - During prion diseases the normal prion protein PrP(C) is refolded into an
      abnormal conformer PrP(Sc). We have studied the PrP(Sc) inhibiting activity of a
      library of synthetic heparan mimetic (HM) biopolymers. HMs are chemically derived
      dextrans obtained by successive substitutions with carboxymethyl, benzylamide,
      and sulfate groups on glucose residues. Some HMs eliminated PrP(Sc) from prion
      infected cells after a 5 day course at 100 ng/ml and were 15 x potent than
      pentosan sulfate in this system. The anti-PrP(Sc) activity of HMs correlated with
      the degree of sulfation but was increased by benzylamidation. HMs did not reduce
      the synthesis of PrP(C) nor its attachment to lipid rafts, but instead blocked
      its conversion into PrP(Sc). The anti-PrP(Sc) HMs also prevented the uptake of
      prion rods by cultured cells. HMs may thus block the interaction of PrP(Sc) with
      a putative cellular receptor, possibly heparan sulfate. HMs provide an attractive
      chemical approach for the synthesis of TSE therapeutic and prophylactic reagents.

PMID- 14637162
TI  - Multiple single-nucleotide polymorphisms in the methylenetetrahydrofolate
      reductase and its truncated pseudogene of 23 inbred strains of mice.
AB  - Reduced 5,10-methylenetetrahydrofolate reductase (MTHFR) results in a number of
      human diseases. To find a model mouse sensitive to these diseases, we analyzed
      single-nucleotide polymorphisms (SNPs) of the mouse Mthfr using 23
      phylogenetically distant strains of mouse. We found five SNPs: two nonsynonymous
      and three synonymous. The CAST/Ei strain has the nonsynonymous SNP L350V and five
      strains (NMRI, KJR, SWN2, MSM, and JF1) have the nonsynonymous SNP S22G. The
      MTHFR activity of CAST/Ei and MSM showed no significant difference in activity or
      thermostability compared with that of C57BL/6J. We also found a pseudogene
      segment of the mouse Mthfr that was not present in human and was more frequently
      variable than the functional gene. These results suggest a possibility that the
      truncated pseudogene may buffer variations of the mouse Mthfr functional gene,
      and the mouse has evolved fewer variations of the gene than human.

PMID- 14637163
TI  - A role for Ca(v)1.3 in rat intestinal calcium absorption.
AB  - Active Ca(2+) absorption through epithelial Ca(2+) channels TRPV5/6 in duodenum
      is activated by hyperpolarisation. However, when diet and Ca(2+) are plentiful,
      digestion products cause depolarisation. We therefore used homology-based PCR
      from a rat jejunal mucosal cDNA preparation to reveal the presence of the
      neuroendocrine L-type isoform Ca(v)1.3alpha(1). Immunocytochemical labelling and
      immunoblotting localised Ca(v)1.3 alpha(1) protein in apical membrane from
      proximal jejunum to mid ileum. Perfusion studies in vivo with 1.25 mM luminal
      Ca(2+) revealed L-type channel activity. Inhibition of glucose absorption with
      phloridzin strongly inhibited 45Ca(2+) absorption; absorption was inhibited by
      nifedipine and Mg(2+) and activated by Bay K 8644, none of which affect TRPV5/6.
      At 10mM Ca(2+), nifedipine inhibited 45Ca(2+) absorption with a time course
      similar to that at 1.25 mM Ca(2+): absorption was therefore channel-mediated
      rather than paracellular. We suggest that in times of dietary sufficiency,
      Ca(v)1.3 may mediate a significant route of Ca(2+) absorption into the body.

PMID- 14637165
TI  - Regional expression patterns of taste receptors and gustducin in the mouse
      tongue.
AB  - In order to understand differences in taste sensitivities of taste bud cells
      between the anterior and posterior part of tongue, it is important to analyze the
      regional expression patterns of genes related to taste signal transduction on the
      tongue. Here we examined the expression pattern of a taste receptor family, the
      T1r family, and gustducin in circumvallate and fungiform papillae of the mouse
      tongue using double-labeled in situ hybridization. Each member of the T1r family
      was expressed in both circumvallate and fungiform papillae with some differences
      in their expression patterns. The most striking difference between fungiform and
      circumvallate papillae was observed in their co-expression patterns of T1r2,
      T1r3, and gustducin. T1r2-positive cells in fungiform papillae co-expressed T1r3
      and gustducin, whereas T1r2 and T1r3 double-positive cells in circumvallate
      papillae merely expressed gustducin. These results suggested that in fungiform
      papillae, gustducin might play a role in the sweet taste signal transduction
      cascade mediated by a sweet receptor based on the T1r2 and T1r3 combination, in
      fungiform papillae.

PMID- 14637164
TI  - Balancer-Cre transgenic mouse germ cells direct the incomplete resolution of a
      tri-loxP-targeted Cyp1a1 allele, producing a conditional knockout allele.
AB  - To generate conditional alleles, genes are commonly engineered to contain
      recognition sites for bacteriophage recombinases, such as Cre recombinase. When
      such motifs (lox sites) flank essential gene sequences, and provided that Cre
      recombinase is expressed, Cre recombinase will excise the flanked sequence
      creating a conditional knockout allele. Targeted conditional alleles contain a
      minimum of three lox sites. It would be desirable to have Cre recombinase perform
      partial resolution (i.e., recombination some of the time between only the two lox
      sites flanking the marker gene). Here we report use of the commercially available
      Balancer2-Cre transgenic mouse line to carry out this function from a tri-loxP
      site-containing cytochrome p450 1A1 (Cyp1a1) targeted allele. Such incomplete
      resolution of this complex locus occurred progressively with age in germ cells of
      male mice; the conditional Cyp1a1 gene was recovered in offspring from mice
      containing the targeted Cyp1a1 allele and the Cre recombinase transgene. Removal
      of the marker gene resulted in a conditional Cyp1a1 allele whose expression was
      indistinguishable from that of the wild-type allele.

PMID- 14637166
TI  - Gastroprotection by vitamin C--a heme oxygenase-1-dependent mechanism?
AB  - Free oxygen radicals contribute to gastric mucosal damage induced by acetylic
      salicylic acid (ASA). Vitamin C has been shown to reduce gastric toxicity of ASA
      in humans. We intended to assess the role of heme oxygenase-1 (HO-1) in this
      process by application of these substances to AGS and KATO III cells. HO-1
      expression was monitored by real-time RT-PCR, Western blot, and HO activity
      measurement. HO-1 mRNA was significantly elevated by either ASA or vitamin C in
      gastric epithelial cells, combination of both substances further increased
      expression. HO-1 protein and enzyme activity rose in cells exposed to vitamin C
      alone or combined with ASA, but not after stimulation with ASA alone. In contrast
      to endothelia, in which ASA simultaneously induces HO-1 mRNA and protein
      expression, gastric epithelial cells require vitamin C to translate HO-1 mRNA
      into active protein, which then may exert gastroprotection by its antioxidant and
      vasodilative properties.

PMID- 14637167
TI  - Inhibition of peroxisome proliferator-activated receptor alpha signaling by
      vitamin D receptor.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid
      receptors that have been implicated to play an important role in lipid and
      glucose homeostasis. PPARalpha potentiates fatty acid catabolism in the liver and
      is activated by the lipid-lowering fibrates, whereas PPARgamma is essential for
      adipocyte differentiation. Here we report that nuclear vitamin D(3) receptor
      (VDR) represses the transcriptional activity of PPARalpha but not PPARgamma in a
      1,25(OH)(2)D(3)-dependent manner. The analysis using chimeric receptors revealed
      that ligand binding domain of PPARalpha and VDR was involved in the molecular
      basis of this functional interaction and that the DNA binding domain of VDR was
      not required for the suppression, suggesting a novel mechanism that might involve
      protein-protein interactions rather than a direct DNA binding. Furthermore, the
      treatment of rat hepatoma H4IIE cells with 1,25(OH)(2)D(3) diminishes the
      induction of AOX mRNA by PPARalpha ligands, Wy14,643. VDR signaling might be
      considered as a factor regulating lipid metabolism via PPARalpha pathway. We
      report here the novel action of VDR in controlling gene expression through
      PPARalpha signaling.

PMID- 14637168
TI  - ik3-2, a relative to ik3-1/Cables, is involved in both p53-mediated and p53
      independent apoptotic pathways.
AB  - ik3-2 is a close relative to ik3-1/Cables, an associator with cdk3 and cdk5. ik3
      1/Cables has been identified to be a candidate tumor suppressor for colon and
      head/neck cancers. In agreement, it has been pointed out that ik3-1/Cables is a
      regulator for both p53- and p73-induced apoptosis [J. Biol. Chem. 277 (2002)
      2951] although ectopic expression of ik3-1/Cables does not induce apoptosis. Here
      we show that adenovirus-mediated overexpression of ik3-2 results in apoptosis of
      p53-intact U2OS cells. ik3-2 binds to p53 in vivo and ectopic coexpression of ik3
      2 enhances apoptosis induced by adenovirus-mediated expression of p53.
      Furthermore, ectopic expression of ik3-2 results in apoptosis of primary p53/Mdm2
      and p53/ARF-null mouse embryo fibroblasts, indicating that ik3-2-induced
      apoptosis is partially p53-independent. Both the highly conserved C-terminal
      cyclin box-homologous domain (ik3-2-C) and the N-terminal region consisting of 70
      amino acids (ik3-2-N) are responsible for ik3-2-mediated enhancement of p53
      induced apoptosis. In contrast, ik3-2-induced p53-independent apoptosis is
      mediated through ik3-2-N. We thus identified ik3-2 as a proapoptotic factor
      involved in both p53-mediated and p53-independent apoptotic pathways.

PMID- 14637169
TI  - Neuroendocrinology of the pancreas; role of brain-gut axis in pancreatic
      secretion.
AB  - Exocrine pancreatic secretion, attributed initially to neural reflexes (nervism),
      was then found to depend also on enterohormones, especially secretin and
      cholecystokinin (CCK), released by the intestinal mucosa and believed to act via
      an endocrine pathway. Recently, CCK and other enterohormones were found to
      stimulate the pancreas by excitation of sensory nerves and by trigger of long
      vagovagal or ("brain-gut axis") enteropancreatic reflexes. Numerous
      neurotransmitters, such as acetylcholine, and certain neuropeptides, such as
      gastrin-releasing peptide (GRP), generated by neurons of the enteric nervous
      system (ENS) of the gut, have been implicated in the regulation of exocrine
      pancreas. Recently, peptides affecting appetite behavior and originating from the
      gut, such as leptin and ghrelin, or from the pancreas, such as pancreatic
      polypeptide and neuropeptide Y, appear to modulate the exocrine pancreas via
      hypothalamic centers. The aim of this review is to highlight the interaction of
      nerves and enterohormones in the regulation of exocrine pancreatic secretion.

PMID- 14637170
TI  - Agonist-induced desensitization and endocytosis of heterodimeric GABAB receptors
      in CHO-K1 cells.
AB  - gamma-Aminobutyric acid B (GABA(B)) receptor is the first discovered G protein
      coupled receptor that requires two subunits, GB1 and GB2, to form a functional
      receptor. Whereas the molecular and functional characteristics of GABA(B)
      receptors have been recently extensively studied, the mechanisms underlying
      receptor desensitization and endocytosis are still poorly understood. We have
      investigated the effect of continuous agonist exposure on the human GABA(B)
      receptor functional response and redistribution when expressed in Chinese hamster
      ovary (CHO-K1) cells. The wild-type GABA(B) receptor-mediated inhibition of the
      adenylate cyclase activity appeared desensitized after 2 h in the presence of
      GABA (100 microM). Fusion proteins were generated by attachment of cyan
      fluorescent protein (CFP) and yellow fluorescent protein (YFP) to GB1 and GB2,
      respectively, and confocal microscopy experiments in intact living cells semi
      stably expressing the constructs were performed. Incubation of co-expressing CFP
      GB1 and YFP-GB2 cells in the presence of GABA (100 microM) for 2 h induced a
      profound receptor internalization, and CFP-GB1 and YFP-GB2 appeared co-localized
      in the endosome (labelled with Cy3-transferrin). The internalization was blocked
      by a selective GABA(B) receptor antagonist. These results represent the first
      clear visualization of agonist-induced internalization of the unique
      heterodimeric GABA(B) receptor.

PMID- 14637171
TI  - Negative functional effects of cyclic GMP are altered by cyclic AMP
      phosphodiesterases in rabbit cardiac myocytes.
AB  - In this study, we tested the hypothesis that the negative functional effects of
      cyclic GMP on cardiac myocytes would be affected by the actions of cyclic GMP on
      cyclic AMP phosphodiesterases. Ventricular myocytes from eight rabbits were used
      to determine the functional and cyclic AMP changes caused by 10(-7), 10(-6), 10(
      5) M 8-Bromo-cGMP alone and after the administration of 10(-6) M milrinone
      (cyclic GMP-inhibited cyclic AMP phosphodiesterase inhibitor) or 10(-6) M erythro
      9-(2-Hydroxy-3-3-nonyl)adenine (EHNA, cyclic GMP-stimulated cyclic AMP
      phosphodiesterase inhibitor). 8-Br-cGMP dose-dependently reduced %shortening by
      35+/-4% of baseline at 10(-5) M. This effect was significantly blunted by EHNA at
      all doses. The maximum rate of shortening was reduced by 31+/-3% by 10(-5) M 8-Br
      cGMP. This effect of 8-Br-cGMP was significantly enhanced (42+/-4%) in the
      milrinone group. A similar pattern was observed in the maximum rate of relaxation
      data. Cyclic AMP levels were significantly increased from a baseline level of
      4.0+/-0.8 pmol/10(5) myocytes by milrinone (+60%), EHNA (+61%) and 8-Br-cGMP
      (+47%). The combination of EHNA plus 8-Br-cGMP increased cyclic AMP levels
      significantly more that the combination of milrinone plus 8-Br-cGMP. Exogenous
      cyclic GMP reduces myocyte function, while raising cyclic AMP possibly through
      cyclic GMP-inhibited cyclic AMP phosphodiesterase effects. Blocking cyclic GMP
      inhibited cyclic AMP phosphodiesterase enhances the functional effects cyclic
      GMP, while blocking cyclic GMP-stimulated cyclic AMP phosphodiesterase reduced
      these effects. The study demonstrated a functional interaction between cyclic GMP
      and cyclic AMP related to the cyclic GMP affected cyclic AMP phosphodiesterases.

PMID- 14637172
TI  - Effects of calycosin on the impairment of barrier function induced by hypoxia in
      human umbilical vein endothelial cells.
AB  - The purpose of the present study was to examine the effects of calycosin, an
      isoflavonoid isolated from Astragali Radix, on the impairment of barrier function
      induced by hypoxia in cultured human umbilical vein endothelial cells. Hypoxia
      induced an increase in endothelial cell monolayer permeability, indicating
      endothelial cell barrier impairment. Endothelial barrier dysfunction induced by
      hypoxia was accompanied by decreases in cytosolic ATP concentration and cAMP
      level, the development of actin stress fibers and intercellular gap formation,
      suggesting that the decreases in cytosolic ATP and cAMP levels and rearrangements
      of F-actin could be associated with an increase in permeability of endothelial
      monolayers. Application of calycosin inhibited the hypoxia-induced increase in
      endothelial permeability in a dose-dependent fashion, which is compatible with
      inhibition of lactate dehydrogenase release, decrease of the fall in ATP and cAMP
      contents, and improvement of F-actin rearrangements. These findings indicate that
      calycosin protected endothelial cells from hypoxia-induced barrier impairment by
      increasing intracellular energetic sources and promoting regeneration of the cAMP
      level, as well as improving cytoskeleton remodeling.

PMID- 14637173
TI  - Antimigraine dotarizine blocks P/Q Ca2+ channels and exocytosis in a voltage
      dependent manner in chromaffin cells.
AB  - The mechanism of blockade of P/Q Ca(2+) channels by antimigraine, dotarizine, was
      studied in voltage-clamped bovine adrenal chromaffin cells. Inward currents
      through P/Q channels were pharmacologically isolated by superfusing the cells
      with omega-conotoxin GVIA (1 microM) plus nifedipine (3 microM). Dotarizine (10
      30 microM) blocked the P/Q fraction of I(Ba) and promoted current inactivation.
      Thus, dotarizine caused a greater blockade of the late I(Ba), compared with
      blockade of the early peak I(Ba). This effect was more prominent, the longer was
      the duration of the depolarising pulse. The blockade of I(Ba) was also greater at
      more depolarising holding potentials (i.e. -60 mV), than was the blockade
      produced at more hyperpolarising holding potentials (i.e. -80 or -110 mV).
      Catecholamine secretory responses to brief pulses (2 s) of a Krebs-HEPES solution
      containing 100 mM K(+) and 2 mM Ca(2+) was blocked by 3 microM dotarizine.
      Blockade was faster and greater when dotarizine was applied on cells that were
      previously depolarised with Krebs-HEPES deprived of Ca(2+) and containing
      increasing concentrations of K(+). This voltage-dependent blockade of P/Q
      channels and exocytosis might be the underlying mechanism explaining the
      dotarizine prophylaxis of migraine attacks.

PMID- 14637174
TI  - Pre- and postsynaptic dopamine mechanisms after repeated nicotine: effects of
      adrenalectomy.
AB  - The reinforcing properties of nicotine may be related to its ability to release
      dopamine in the nucleus accumbens and to increase locomotor activity in
      experimental animals. Both these effects are sensitized following repeated drug
      exposure, a phenomenon that may underlie important aspects of addiction. Adrenal
      steroids may be involved both in positive reinforcement and in sensitization.
      Adrenalectomy hampers, e.g., the induction of locomotor sensitization to
      nicotine, and cross-sensitization between stress and psychostimulants may
      develop. Here, the effect of adrenalectomy on postsynaptic and presynaptic
      changes of the mesolimbic dopamine system in association with nicotine
      sensitization was examined. Adrenalectomy or sham-operated rats received daily
      nicotine (0.4 mg/kg s.c.) or vehicle for 15 days, after which the locomotor
      responses to nicotine (0.2 mg/kg s.c.) and the dopamine D1/D2 receptor agonist
      apomorphine (1.0 mg/kg s.c. or 100 microM in the nucleus accumbens by reversed
      microdialysis) were recorded. In addition, accumbal dopamine output was monitored
      by in vivo microdialysis after nicotine challenge. Sham/nicotine animals showed a
      sensitized locomotor response to systemic and local apomorphine compared to all
      other groups, including the adrenalectomized/nicotine group. Nicotine increased
      accumbal dopamine output in all animals. In contrast, nicotine induced a
      pronounced increase in locomotor activity in the sham/nicotine animals compared
      to the other vehicle group and the adrenalectomized animals. These results
      indicate that adrenal steroids are involved in the induction of the postsynaptic
      component of nicotine sensitization, whereas their involvement in tentative
      presynaptic changes remains unclear.

PMID- 14637176
TI  - Anxiolytic effects of the novel anti-epileptic drug levetiracetam in the elevated
      plus-maze test in the rat.
AB  - There is clinical evidence of anxiolytic action of several anti-epileptic drugs.
      We evaluated the effects of levetiracetam (Keppra), a new generation anti
      epileptic drug, in the plus-maze animal test for anxiolytic activity.
      Levetiracetam at 17 and 54 mg/kg intraperitoneally (i.p.) was without effect when
      tested in naive rats. A modified version of the test was subsequently used in
      which open-arm exploration was decreased by exposure of the rats to a four-open
      arm maze 24 h prior to drug treatment and testing. Under these conditions of
      enhanced anxiety, levetiracetam, 5.4 to 54 mg/kg, dose-dependently increased open
      arm exploration. Chlordiazepoxide 5 mg/kg had similar effects although buspirone
      0.1 to 1.0 mg/kg was inactive. The results with levetiracetam substantiate
      similar findings of its anxiolytic actions against chlordiazepoxide withdrawal
      induced anxiety in mice and in a modified Vogel test in rats and support a
      potential clinical use of this drug in anxiety states.

PMID- 14637175
TI  - Endogenous glucocorticoids inhibit scratching behavior induced by the
      administration of compound 48/80 in mice.
AB  - In this study, we investigated the effects of endogenous glucocorticoids on the
      compound 48/80 (a condensation product of N-methyl-p-methoxyphenethylamine with
      formaldehyde)-induced mouse scratching behavior using either RU-486
      (mifepristone), a glucocorticoid receptor antagonist, or a surgical resection of
      the adrenal glands. Subcutaneous injection of compound 48/80 induced not only a
      corticosterone elevation in the plasma but also an enhanced expression of
      corticotropin releasing hormone (CRH) mRNA in the paraventricular nucleus, which
      thus suggests that hypothalamic-pituitary-adrenal axis is activated by the
      compound 48/80-induced cutaneous reaction. Inhibition of such an endogenous
      glucocorticoid activity by RU-486 significantly increased the degree of
      scratching behavior at not only the early-phase (<60 min) but also the late-phase
      (>60 min) time course after the injection of compound 48/80. Since the elevation
      of the histamine levels in the plasma in the RU-486-treated mice was no longer
      found in late-phase scratching behavior, these results thus indicate that
      histamine is a dominant mediator responsible for early-phase scratching behavior,
      while different mediators other than histamine may be also involved in the
      induction of late-phase scratching behavior. Moreover, surgical removal of
      adrenal glands also significantly increased the compound 48/80-induced scratching
      behavior without affecting anxiety and locomotor parameters, indicating that
      endogenous glucocorticoids exert their anti-pururitogenic effects independently
      of changes in behavioral performance. In conclusion, endogenous glucocorticoid
      activity was found to suppress the compound 48/80-induced scratching behavior in
      mice.

PMID- 14637177
TI  - 5-HT(1A) receptor full agonist, 8-OH-DPAT, exerts antidepressant-like effects in
      the forced swim test in ACTH-treated rats.
AB  - We examined the effect of adrenocorticotropic hormone (ACTH) on the
      immobilization of rats in the forced swim test after administration of the 5
      HT(1A) receptor agonist, 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT).
      Imipramine (3-30 mg/kg, i.p.) or 8-OH-DPAT (0.1-1 mg/kg, s.c.) significantly
      decreased the duration of immobility in normal rats. The immobility-decreasing
      effect of imipramine was blocked when ACTH was administered for 14 days. On the
      other hand, the immobility-decreasing effect induced by 8-OH-DPAT was not blocked
      by chronic administration of ACTH for 14 days. These findings indicate that 8-OH
      DPAT can be useful in an animal model of depressive conditions resistant to
      antidepressant treatment.

PMID- 14637178
TI  - Ovariectomy aggravates nifedipine-induced flushing of tail skin in mice.
AB  - Flushing is one of the most common vasodilation-related adverse effects
      associated with Ca(2+) channel antagonist treatment. This symptom is known to
      occur more frequently in women than men. The present study aimed at investigating
      the effect of ovariectomy on nifedipine-induced flushing in mice. Ovariectomy
      markedly increased the tail skin temperature, a parameter of skin flushing,
      induced by nifedipine at a dose showing no influence on blood pressure. This
      event was blocked by estradiol replacement. Estrogen withdrawal is, therefore,
      included in the risk factors for nifedipine-induced flushing and this risk is
      lessened by estrogen replacement.

PMID- 14637179
TI  - Carvedilol blockade of rat myocardial alpha1-adrenoceptors.
AB  - Carvedilol is a combined alpha(1)- and beta-adrenoceptor antagonist. The ability
      of carvedilol to antagonize functional effects mediated through myocardial
      alpha(1)-adrenoceptors has never been investigated. We tested the ability of
      carvedilol to antagonize the inotropic effect mediated by myocardial alpha(1)
      adrenoceptors compared to the antagonism of beta-adrenoceptors. Papillary muscles
      from rat heart left ventricle were mounted in an organ bath and concentration
      response experiments for the inotropic effects of separate alpha(1)- and beta
      adrenoceptor stimulation were performed in the absence and presence of
      carvedilol. Carvedilol antagonized myocardial alpha(1)-adrenoceptors with an
      inhibition constant (K(i)) of 11.0+/-3.0 nmol/l and the functional experiments
      were supported by radioligand-binding studies. Corresponding functional studies
      on the response to beta-adrenoceptor stimulation revealed a K(i) of 1.2+/-0.35
      nmol/l. Thus, carvedilol antagonizes the myocardial alpha(1)-adrenoceptors with a
      9-fold lower potency than the beta-adrenoceptors. Antagonism of myocardial
      alpha(1)-adrenoceptor evoked effects may contribute to clinical effects of
      carvedilol.

PMID- 14637180
TI  - Tempol, an antioxidant, restores endothelium-derived hyperpolarizing factor
      mediated vasodilation during hypertension.
AB  - Acetylcholine releases a non-prostanoid endothelium-derived hyperpolarizing
      factor (EDHF) and nitric oxide from physiological salt solution perfused rat
      mesenteric arteries. This study reports an impairment in EDHF-mediated
      vasodilation in deoxycorticosterone acetate (DOCA)-salt hypertensive versus
      control normotensive rats. Nitric oxide-mediated vasodilation to acetylcholine
      was not altered in the animals. We hypothesize that free radical species
      generated as by-products of arachidonic acid metabolism contribute to impaired
      EDHF-mediated dilation in DOCA-salt hypertension. With or without reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) as co-factor, arterial
      microsomes generate free radical species upon incubation with arachidonic acid.
      The production of free radicals was significantly higher in DOCA-salt versus
      control rat microsomes, and was totally eliminated by addition of cyclooxygenase
      2 inhibitors NS-398 or celecoxib at 30 microM. Treatment of DOCA-salt rats with
      tempol (an antioxidant; 15 mg/kg, i.p., 21 days) alleviates hypertension;
      improves acetylcholine-induced EDHF-mediated vasodilation in DOCA-salt rats, and
      decreases arachidonic acid-driven microsomal free radical production. Serum level
      of 8-isoprostanes is elevated in DOCA-salt hypertension versus control or sham
      salt rats, and the increase was reversed by tempol treatment. These results show
      that EDHF-mediated dilation of rat mesenteric arteries is impaired in DOCA-salt
      induced hypertension. Our data also suggest that cyclooxygenase-2 mediates free
      radical production, and that free radicals modulate the EDHF-mediated vascular
      response in DOCA-salt induced hypertension.

PMID- 14637181
TI  - Effect of antiproliferative agents on vascular function in normal and in vitro
      balloon-injured porcine coronary arteries.
AB  - Local infusion of antiproliferative agents following coronary balloon angioplasty
      is used in vivo. This study examined the effects of the antiproliferative agents
      paclitaxel (5-beta, 20-Epoxy-1,2-alpha,4,7-beta,10-beta,13-alpha-Hexahydroxy-Tax
      11-en-9-one 4,10-Diacetate 2_Benzoate 13-Ester with (2R,3S)-N-Benzoyl-3
      Phenylisoserine; 10 and 50 microM), farnesyl protein transferase inhibitor III
      (FPT III, (E,E)-2-[2-Oxo-2-[(3,7,11-trimethyl-2,6,10-dodecatrienyl) oxy] amino]
      ethyl] phosphonic acid, (2,2-dimethyl-1-oxopropoxy) methyl ester, sodium); 10 and
      25 microM), perillyl alcohol (4-isopropenyl-cyclohexenecarbinol; 1 and 2 mM) and
      Van 10/4 (Decahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulen-4-o-[2-(3
      methylpent-2-enoyl)-fucopyranoside]; 10 and 25 microM) on normal and in vitro
      balloon-injured porcine coronary arteries. Short-term (30 min) incubation had no
      effect on contraction or relaxation. Overnight incubation with 25 microM Van 10/4
      attenuated contraction while perillyl alcohol abolished contractility completely.
      Endothelium-dependent relaxation was significantly attenuated by the higher
      concentration of paclitaxel, FPT III and Van 10/4. Stretch injury significantly
      enhanced sensitivity to 3-morpholinosydnonimine (SIN-1) while attenuating
      relaxation to calcimycin. Drug incubation (15 min) had no effect on these
      responses. In conclusion, paclitaxel, FPT III and Van 10/4 have no detrimental
      effects on vascular function after short-term administration to normal or stretch
      injured arteries.

PMID- 14637182
TI  - In vivo coronary effects of endothelin-1 after ischemia-reperfusion. Role of
      nitric oxide and prostanoids.
AB  - To examine the effects of reperfusion after short and prolonged ischemia on the
      coronary action of endothelin-1, left circumflex coronary artery flow was
      electromagnetically measured, and 15- or 60-min occlusion of this artery followed
      by reperfusion was induced in anesthetized goats. In non-treated animals, during
      reperfusion after 15-min occlusion, the duration but not the peak of endothelin-1
      induced coronary effects (0.01-0.3 nmol) was increased, and the effects of
      acetylcholine (3-100 ng) were unchanged. During reperfusion after 60-min
      occlusion, the peak and duration of endothelin-1-induced effects were increased
      whereas those of acetylcholine were decreased. N(w)-nitro-L-arginine methyl
      esther (L-NAME) treatment did not modify the peak and duration of the coronary
      effects of endothelin-1 during reperfusion after both durations of occlusion.
      This treatment inhibited the effects of the two higher doses but not those of the
      two lower doses of acetylcholine during reperfusion after 15-min occlusion, and
      it did not modify the effects of any dose of this drug during reperfusion after
      60-min occlusion. Meclofenamate treatment did not modify the coronary effects of
      endothelin-1 and acetylcholine during reperfusion after both durations of
      occlusion. These results suggest that ischemia-reperfusion increases the coronary
      response to endothelin-1, which is more pronounced during reperfusion after
      prolonged than after brief ischemia, and that this increased response is probably
      related to inhibition of nitric oxide release, without involvement of
      prostanoids.

PMID- 14637183
TI  - Nadroparine inhibits the hypersensitivity response in the conjunctiva.
AB  - This study sought to investigate the effects of nadroparine on an in vivo
      experimental model of type I hypersensitivity response in the rat conjunctiva.
      Following drug application onto the eye, either before or after challenge with
      the mast cell degranulator, basic polyamine compound 48/80, the conjunctival
      histamine content and the nitrite levels in the conjunctival lavage fluid were
      quantified fluorometrically and spectrophotometrically, respectively.
      Instillation into the eye of nadroparine inhibited the C48/80-induced decreases
      in conjunctival histamine and the delayed increases in nitrite levels, without
      influencing basal mediator levels. Protamine did not induce histamine release and
      only partially reversed the effects of nadroparine post-challenge, yet it had no
      effect on the protective action of the drug when administered prior to
      degranulation. The results showed that nadroparine was equally effective in
      attenuating the effects of compound 48/80 in the eye when administered topically
      either before or after challenge.

PMID- 14637184
TI  - Insulin induces a hypercontractile airway smooth muscle phenotype.
AB  - This study aims to investigate the effects of insulin on bovine tracheal smooth
      muscle phenotype in vitro. Contractility of muscle strips and DNA-synthesis
      ([3H]thymidine incorporation) of isolated cells were used as parameters for
      smooth muscle phenotyping. Insulin (1 microM) was mitogenic for bovine tracheal
      smooth muscle and potentiated DNA-synthesis induced by other growth factors. In
      contrast, after pretreatment of unpassaged bovine tracheal smooth muscle cells in
      culture, the mitogenic response induced by growth factors was strongly
      diminished, with no difference in the basal incorporation. Pretreatment of bovine
      tracheal smooth muscle strips in organ culture with insulin increased maximal
      contraction to methacholine and KCl. These results show that insulin acutely
      augments DNA-synthesis in the presence of other growth factors. In contrast,
      insulin pretreatment induces a hypercontractile phenotype with a decreased
      mitogenic capacity. This mechanism may be involved in the putative negative
      association between asthma and type I diabetes. In addition, these findings may
      have implications for the use of aerosolized insulin in diabetes mellitus.

PMID- 14637185
TI  - Antivirals interacting with hepatitis B virus core protein and core mutations may
      misdirect capsid assembly in a similar fashion.
AB  - Recently, heteroarylpyrimidines (HAP) have been identified as potent inhibitors
      of capsid maturation. Here we discuss the HAP mode of action comparing the
      aggregation phenotype of wild-type and mutant core proteins with the respective
      phenotype imposed by HAP or other agents interacting with core protein. Pertinent
      tests include core fusion protein-mediated transactivation in a two-hybrid system
      and capsid formation. The finding that transactivation appeared to be unaffected
      by HAP, or by mutations preventing assembly, is surprising and raises the
      question for the structure of the interacting hybrid core proteins: Are they
      monomers, dimers or even oligomers? A direct activity of core fusion monomers is
      not excluded but considered to be highly unlikely due to rapid homodimerisation.
      A role of core fusion dimers in transactivation would indicate distinct
      interactions with a differential sensitivity to HAP. Regarding significance of
      data gained in two-hybrid systems, caution is necessary, since the site of
      transactivation is the nucleus, whereas the real site of the core protein
      interactions during replication is the cytoplasm. Apparently, HAP leave the
      monomer-monomer interface of HBV core protein unaffected but prevent capsid
      maturation by interacting with a region known to be crucial for dimer
      multimerisation and formation of stable capsids. It is suggested to use
      antivirals as tools for the elucidation of early steps in genome replication and
      capsid assembly. A frame for this could be the hypothesis that the virus uses
      soluble core protein, namely intracellular maturation intermediates of HbeAg for
      a core targeted self-restriction of replication.

PMID- 14637186
TI  - Involvement of tumor suppressor protein p53 and p38 MAPK in caffeic acid
      phenethyl ester-induced apoptosis of C6 glioma cells.
AB  - Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many
      biological and pharmacological activities including antioxidant, anti
      inflammation, antiviral action, and anticancer effect. Our previous studies
      showed that CAPE exhibited significant cytotoxicity in oral cancer cells. Herein
      we further investigated the cytotoxicity potential of CAPE and the mechanism of
      its action in C6 glioma cells. The data exhibited that C6 glioma cells underwent
      internucleosomal DNA fragmentation 24 hr after the treatment of CAPE (50 microM).
      The proportion of C6 glioma cells with hypodiploid nuclei was increased to 24% at
      36 hr after the exposure. Further results showed that CAPE induced the release of
      cytochrome c from mitochondria into cytosol, and the activation of CPP32. CAPE
      application also enhanced the expression of p53, Bax, and Bak. Finally, the
      potential signaling components underlying CAPE induction of apoptosis were
      elucidated. We found that CAPE activated extracellular signal-regulated kinase
      (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in C6 glioma cells.
      More importantly, p38 kinase formed a complex with p53 after the treatment of
      CAPE for 0.5 hr. The expression of p53, phospho-serine 15 of p53, and Bax, and
      inactivate form of CPP32 was suppressed by a pretreatment of a specific p38 MAPK
      inhibitor, SB203580. The resultant data suggest that p38 MAPK mediated the CAPE
      induced p53-dependent apoptosis in C6 glioma cells.

PMID- 14637187
TI  - Mechanism underlying cytotoxicity of thialysine, lysine analog, toward human
      acute leukemia Jurkat T cells.
AB  - We first report the mechanism for the inhibitory effect of the lysine analog,
      thialysine on human acute leukemia Jurkat T cells. When Jurkat T cells were
      treated with thialysine (0.32-2.5 mM), apoptotic cell death along with several
      biochemical events such as mitochondrial cytochrome c release, caspase-9
      activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase,
      and DNA fragmentation was induced in a dose- and time-dependent manner. However,
      these thialysine-induced apoptotic events were significantly abrogated by an
      ectopic expression of Bcl-xL, which is known to block mitochondrial cytochrome c
      release. Decylubiquinone, a mitochondrial permeability transition pore inhibitor,
      also suppressed thialysine-induced apoptotic events. Comparison of the thialysine
      induced alterations in the cell cycle distribution between Jurkat T cells
      transfected with Bcl-xL gene (J/Bcl-xL) and Jurkat T cells transfected with
      vector (J/Neo) revealed that the apoptotic cells were mainly derived from the
      cells accumulated in S and G2/M phases following thialysine treatment. The
      interruption of cell cycle progression in the presence of thialysine was
      accompanied by a significant decline in the protein level of cdk4, cdk6, cdc2,
      cyclin A, cyclin B1, and cyclin E. These results demonstrate that the cytotoxic
      activity of thialysine toward Jurkat T cells is attributable to not only
      apoptotic cell death mediated by a mitochondria-dependent death signaling
      pathway, but also interruption of cell cycle progression by a massive down
      regulation in the level of cdks and cyclins.

PMID- 14637188
TI  - Induction of the mitochondrial permeability transition by selenium compounds
      mediated by oxidation of the protein thiol groups and generation of the
      superoxide.
AB  - The cancer chemopreventive effect of selenium compounds cannot be fully explained
      by the role of selenium as a component of antioxidant enzymes, suggesting that
      other mechanisms, such as thiol oxidation or free radical generation, also
      underlie this effect. The toxicities of six different selenium compounds
      (selenite, selenate, selenocystine, selenocystamine, selenodioxide, and
      selenomethionine) have now been compared in HepG2 human hepatoma cells and
      isolated rat liver mitochondria. Selenite, selenocystine, and selenodioxide
      induced apoptosis in HepG2 cells and mediated oxidation of protein thiol groups
      in both HepG2 cells and isolated mitochondria. Selenocystamine oxidized protein
      thiol groups in isolated mitochondria and crude extracts of HepG2 cells but not
      in intact HepG2 cells, suggesting that this compound is not able to cross the
      cell membrane. The selenium compounds capable of oxidizing thiol groups also
      induced the mitochondrial permeability transition (MPT) in isolated mitochondria.
      Furthermore, they generated the superoxide (O(2) .-) on reaction with glutathione
      in the presence of mitochondria, and an O(2) .-) scavenger inhibited their
      induction of the MPT. These results suggest that the pro-apoptotic action of
      selenium compounds is mediated by both thiol oxidation and the generation of O(2)
      .-), both of which contribute to opening of the MPT pore.

PMID- 14637189
TI  - Transient induction of cytochromes P450 1A1 and 1B1 in MCF-7 human breast cancer
      cells by indirubin.
AB  - The aryl hydrocarbon receptor (AhR), when activated by exogenous ligands such as
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), regulates expression of several phase
      I and phase II enzymes and is also involved in the regulation of cell
      proliferation. Several studies suggest that endogenous AhR ligand(s) may exist.
      One putative endogenous ligand is indirubin, which was recently identified in
      human urine and bovine serum. We determined the effect of indirubin in MCF-7
      breast cancer cells on induction of the activities of cytochromes P450 (CYP) 1A1
      and 1B1, as measured by estradiol and ethoxyresorufin metabolism, and on
      induction of the CYP1A1 and CYP1B1 mRNAs. With 4-hr exposure, the effects of
      indirubin and TCDD at 10nM on CYP activity were comparable, but the effects of
      indirubin, unlike those of TCDD, were transitory. Indirubin-induced
      ethoxyresorufin-O-deethylase activity was maximal by 6-9 hr post-exposure and had
      disappeared by 24 hr, whereas TCDD-induced activities remained elevated for at
      least 72 hr. The effects of indirubin on CYP mRNA induction were maximal at 3 hr.
      Indirubin was metabolized by microsomes containing cDNA-expressed human CYP1A1 or
      CYP1B1. The potency of indirubin was comparable to that of TCDD in a CYP1B1
      promoter-driven luciferase assay, when MCF-7 cells were co-exposed to the AhR
      ligands together with the CYP inhibitor, ellipticine. Thus, if indirubin is an
      endogenous AhR ligand, then AhR-mediated signaling by indirubin is likely to be
      transient and tightly controlled by the ability of indirubin to induce CYP1A1 and
      CYP1B1, and hence its own metabolism.

PMID- 14637190
TI  - Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity.
AB  - Curcumin (diferuloylmethane) is a well-known agent with anti-inflammatory,
      antioxidant, and anticarcinogenic properties. In this study, we observed that
      curcumin inhibited the kinase activity of v-Src, which led to a decrease in
      tyrosyl substrate phosphorylation of Shc, cortactin, and FAK. Our in vitro kinase
      experiment revealed that the inhibitory effect of curcumin on Src could be
      direct. Consistent with the abrogation of Src activity was the reduction of Src
      Tyr-416 phosphorylation, Src-mediated Shc-Tyr-317 phosphorylation, decreased ERK
      activation, and cell proliferation in v-Src transformed cells. Remarkably,
      curcumin not only exerted its negative effect on FAK via the disappearance of Src
      mediated FAK phosphorylation, but also directly inhibited its enzymatic activity.
      Concurrent to reduced cortactin tyrosyl phosphorylation and FAK kinase activity
      was the abolishment of v-Src-mediated cell mobility. To our knowledge, this is
      the first report indicating that curcumin can retard cellular growth and
      migration via downregulation of Src and FAK kinase activity.

PMID- 14637191
TI  - Effects of cytochrome b(5) on drug oxidation activities of human cytochrome P450
      (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7.
AB  - Effects of cytochrome b(5) (b(5)) on catalytic activities of human cytochrome
      P450 (CYP) 3A5, CYP3A4, and CYP3A7 coexpressed with human NADPH-cytochrome P450
      reductase in Escherichia coli membranes were investigated using 14 substrates.
      The activities of CYP3A5 were enhanced by addition of b(5) in approximately one
      third of the substrates employed in this study. Such enhancement by b(5) was
      roughly similar to that of CYP3A4, while the activities of CYP3A7 were not
      enhanced by b(5) with any substrates employed. V(max) values for midazolam 1'
      hydroxylation and amitriptyline N-demethylation by CYP3A5 were increased about
      twice by addition of b(5), which was also seen with CYP3A4, although the extent
      of the effects of b(5) on S(50) (K(m)) and Hill coefficient differed dependent on
      substrates used. In contrast, b(5) did not alter any of these kinetic parameters
      of CYP3A7. The effects of b(5) on kinetic parameters of CYP3A5 were similar to
      those of CYP3A4 but not CYP3A7. These results suggest that roles of b(5) in drug
      oxidation activities of CYP3A5 and CYP3A4 are different from those of CYP3A7.

PMID- 14637192
TI  - Colchicine induces membrane-associated activation of matrix metalloproteinase-2
      in osteosarcoma cells in an S100A4-independent manner.
AB  - Like the metastasis-associated protein S100A4, matrix metalloproteinases (MMPs)
      and their tissue inhibitors (TIMPs) are important in physiological and
      pathological conditions. Previously, we showed that S100A4 is involved in the
      regulation of MMPs and TIMPs, and in the present work we have investigated
      whether the anti-inflammatory and microtubule-disrupting drug colchicine has an
      effect on the expression of these proteins in osteosarcoma cell lines (OHS) with
      high and low levels of S100A4. Colchicine treatment of the various OHS cells
      resulted in an increased expression of MT1-MMP and TIMP-2 mRNA, and a
      corresponding increase of these two proteins in isolated cell membranes.
      Colchicine-treated cells produced more of the activated form of MMP-2 than
      control cells. However, the drug did not affect the amount of MMP-2 and TIMP-1
      mRNA or protein, and it reduced the S100A4 mRNA expression. Isolated cell
      membranes from the colchicine-treated cells were more effective in activating
      exogenous proMMP-2 than membranes from control cells, and inhibitory studies
      indicated that it was the colchicine-induced increase in MT1-MMP that caused the
      increased activation of endogenous MMP-2. A peptide inhibitor of nuclear factor
      kappaB nuclear translocation, SN50, blocked the colchicine-induced activation of
      proMMP-2 and reduced the synthesis of MMP-2 in colchicine-treated cells, but not
      in control cells. It can be concluded that colchicine modulates the expression of
      MT1-MMP and TIMP-2 and hence the activation of proMMP-2 independently of the
      S100A4 level in osteosarcoma cells.

PMID- 14637193
TI  - Bilirubin and S-nitrosothiols interaction: evidence for a possible role of
      bilirubin as a scavenger of nitric oxide.
AB  - Bilirubin (BR), the final product of heme catabolism, plays a crucial role in the
      defense against reactive oxygen species in various cell types. In this study, we
      addressed the hypothesis that BR can act as a physiological scavenger of nitric
      oxide (NO), a gaseous mediator involved in many cellular functions and able to
      trigger the formation of reactive nitrogen species with pro-oxidant activity. We
      found that S-nitrosocysteine (SNOC) and S-nitrosoglutathione (GSNO), which have a
      half-life of 0.52+/-0.07 hr and 38+/-5 hr and release NO at a constant rate of
      1.42+/-0.2 hr(-1) and 0.018+/-0.002 hr(-1), respectively, were able to decrease
      BR half-life in a concentration-dependent manner under physiological conditions.
      This effect appears to be dependent on NO formation as L-cysteine and GSH did not
      affect BR consumption and nitrite was four to five times less efficient than SNOC
      in reducing BR half-life. Oxyhemoglobin, a well-known scavenger of NO, protected
      BR from SNOC-mediated degradation. In addition, the reaction between SNOC/GSNO
      and BR modified the absorption spectrum of the bile pigment showing a gradual
      increase in the absorbance at 316 nm. This change in the BR spectrum indicates
      that the bile pigment could be a target for N-nitrosation reactions, since it
      resembles the modifications occurred when other molecules such as di-peptides and
      uric acid are nitrosated. Taken together, these data suggest that BR should not
      be considered only as an endogenous antioxidant but also as a molecule with the
      potential ability to counteract intracellular nitrosative stress reactions.

PMID- 14637194
TI  - Inhibition of arterial contraction by dinitrosyl-iron complexes: critical role of
      the thiol ligand in determining rate of nitric oxide (NO) release and formation
      of releasable NO stores by S-nitrosation.
AB  - The inhibition of arterial tone produced by two nitric oxide (NO) derivatives of
      biological relevance, dinitrosyl-iron complexes with cysteine (DNIC-CYS) or with
      glutathione (DNIC-GSH), was compared. Both compounds induced vasorelaxation
      within the same concentration range (3-300 nM) in endothelium-denuded rat aortic
      rings. Consistent with a faster rate of NO release from DNIC-CYS than from DNIC
      GSH, the relaxant effect of DNIC-CYS was rapid in onset and tended to recover
      with time, whereas the one of DNIC-GSH developed slowly and was sustained. In
      addition, DNIC-GSH (0.3 and 1 microM) but not DNIC-CYS (1 microM) induced, even
      after washout of the drug, a persistent hyporesponsiveness to vasoconstrictors
      and a relaxant effect of low molecular weight thiols like N-acetylcysteine (NAC,
      which can displace NO from preformed NO stores). Both effects of DNIC-GSH were
      associated with elevation of cyclic GMP content and were attenuated by NO
      scavengers or a cyclic GMP-dependent protein kinases inhibitor. In rings
      previously exposed to DNIC-GSH, addition of mercuric chloride (which can cleave
      the cysteine-NO bond of S-nitrosothiols) elicited relaxation, completely blunted
      the one of NAC and also abolished the persistent elevation of NO content. In
      conclusion, this study shows that whereas both DNIC-CYS and DNIC-GSH elicited a
      NO release-associated relaxant effect in isolated arteries, only DNIC-GSH induced
      an inhibition of contraction which persisted after drug removal. The persistent
      effect of DNIC-GSH was attributed to the formation of releasable NO stores in
      arterial tissue, most probably as S-nitrosothiols. Thus, the nature of the thiol
      ligand plays a critical role in determining the mechanisms and duration of the
      effect of LMW-DNIC in arteries.

PMID- 14637195
TI  - Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.
AB  - Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of
      licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver
      mitochondria at micromolar concentrations induces swelling, loss of membrane
      potential, pyridine nucleotide oxidation, and release of cytochrome c and
      apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented
      by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations
      indicate that glycyrrhetinic acid is a potent inducer of mitochondrial
      permeability transition and can trigger the pro-apoptotic pathway.

PMID- 14637196
TI  - Ecteinascidin-743 drug resistance in sarcoma cells: transcriptional and cellular
      alterations.
AB  - A human chondrosarcoma cell line, CS-1, was treated successively with increasing
      concentrations of the marine chemotherapeutic Ecteinascidin-743 (ET-743),
      yielding a variant cell line displaying a significant degree of resistance to the
      cytotoxic action of this drug. Various experiments were performed to discern
      molecular aberrations between the parent and resistant cell line, and also
      identify potential molecular markers indicative of drug resistance. Although no
      significant differences in the levels of membrane transporters such as P
      glycoprotein or multidrug resistance protein 1 (MRP1) were detected, the cell
      migratory ability of the ET-743-resistant cell variant was reduced, as was its
      attachment capability to gelatin-coated cell culture dishes. Staining of the
      actin-containing cytoskeleton with fluorescent-labeled phalloidin revealed marked
      differences in the cytoskeleton architecture between the parent and ET-743
      resistant CS-1 cell lines. Comparison of serum-free conditioned medium from both
      cell lines showed conspicuous differences in the levels of several proteins,
      including a quartet of high molecular weight proteins (> or =140 kDa). The
      protein sequences of two of these high molecular weight proteins, present at
      significantly higher concentrations in conditioned medium obtained from the
      parent cell line, corresponded to subunits of types I and IV collagen. Analysis
      of type I collagen alpha1 chain mRNA revealed a significantly lower level in the
      ET-743-resistant CS-1 cell line. Thus, prolonged exposure to ET-743 may cause
      changes in cell function through cytoskeleton rearrangement and/or modulation of
      collagen levels.

PMID- 14637197
TI  - Naturally occurring 2'-hydroxyl-substituted flavonoids as high-affinity
      benzodiazepine site ligands.
AB  - Screening of traditional medicines has proven invaluable to drug development and
      discovery. Utilizing activity-guided purification, we previously reported the
      isolation of a list of flavonoids from the medicinal herb Scutellaria baicalensis
      Georgi, one of which manifested an affinity for the benzodiazepine receptor
      (BDZR) comparable to that of the synthetic anxiolytic diazepam (K(i)=6.4 nM). In
      the present study, this high-affinity, naturally occurring flavonoid derivative,
      5,7,2'-trihydroxy-6,8-dimethoxyflavone (K36), was chosen for further functional
      and behavioral characterization. K36 inhibited [3H]flunitrazepam binding to
      native BDZR with a K(i) value of 6.05 nM. In electrophysiological experiments K36
      potentiated currents mediated by rat recombinant alpha(1)beta(2)gamma(2) GABA(A)
      receptors expressed in Xenopus oocytes. This potentiation was characterized by a
      threshold (1 nM) and half-maximal stimulation (24 nM) similar to diazepam. This
      enhancement was demonstrated to act via the BDZR, since co-application of 1
      microM of the BDZR antagonist Ro15-1788 reversed the potentiation. Oral
      administration of K36 produced significant BDZR-mediated anxiolysis in the mice
      elevated plus-maze, which was abolished upon co-administration of Ro15-1788.
      Sedation, myorelaxation and motor incoordination were not observed in the chosen
      dosage regimen. Structure-activity relationships utilizing synthetic flavonoids
      with different 2' substituents on the flavone backbone supported that 2'-hydroxyl
      substitution is a critical moiety on flavonoids with regard to BDZR affinities.
      These results further underlined the potential of flavonoids as therapeutics for
      the treatment of BDZR-associated syndromes.

PMID- 14637198
TI  - Inhibition of plasmalemmal Na(+)/Ca(2+) exchange by mitochondrial Na(+)/Ca(2+)
      exchange inhibitor 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin
      2(3H)-one (CGP-37157) in cerebellar granule cells.
AB  - In the heart, 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)
      one (CGP-37157) inhibits mitochondrial but not sarcolemmal Na(+)/Ca(2+) exchange.
      Therefore, CGP-37157 is often used as an experimental tool to study the role of
      mitochondrial Na(+)/Ca(2+) exchange in Ca(2+) homeostasis in various cells,
      including neurons. However, neurons express several K(+)-dependent (NCKX) and/or
      K(+)-independent (NCX) isoforms of plasmalemmal Na(+)/Ca(2+) exchange not
      expressed in the sarcolemma. Because it has never been determined whether CGP
      37157 inhibits plasmalemmal NCKX and/or NCX isoforms in neurons, we tested this
      possibility. As an index of NCKX and/or NCX activity, we studied Na-dependent and
      gramicidin-induced 45Ca(2+) accumulation in the presence and absence of K(+),
      respectively. In primary cultures of cerebellar granule cells, CGP-37157 with
      IC(50) of 13 microM inhibited over 70% of plasmalemmal NCX activity (P<0.01) but
      not NCKX activity. Our data suggest that the effects of CGP-37157 on neuronal
      Ca(2+) homeostasis include inhibition of certain plasmalemmal NCX isoform(s).
      Because cerebellar granule cells robustly express NCX3 transcripts, which are not
      expressed in the heart, it appears that this isoform may be CGP-37157 sensitive.

PMID- 14637199
TI  - Selective agonist binding of (S)-2-amino-3-(3-hydroxy-5-methyl-4
      isoxazolyl)propionic acid (AMPA) and 2S-(2alpha,3beta,4beta)-2-carboxy-4-(1
      methylethenyl)-3-pyrrolidineacetic acid (kainate) receptors: a molecular modeling
      study.
AB  - Molecular models were constructed, using the published X-ray structure of rat
      glutamate receptor 2 (GluR2), for the ligand-binding domains of the human (S)-2
      amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA)- and kainate
      selective ionotropic glutamate receptors (iGluRs): GluR1-7 and KA1-2. Based on
      the analysis of the known X-ray structures of GluR2 in complex with glutamate,
      kainate, and AMPA, we have constructed binding motifs (relative positioning of a
      ligand in the binding site and the physico-chemical interactions that take place)
      for selected agonist ligands and found explanations for ligand-binding
      selectivity to homomeric receptors among the different iGluRs. Even a single
      sequence difference can explain significant differences in ligand-binding
      affinities between two receptors. In total, there are seven residues surrounding
      the binding cavity that affect agonist selectivity: in GluR2, these residues are
      Pro478, Thr480, Leu650, Ser654, Thr686, Tyr702, and Met708. Each of these seven
      positions has been shown, or is predicted, to influence the presence of one or
      more water molecules that, when present, may form bridging hydrogen bonds between
      particular ligands and receptors. By using this knowledge it should be possible
      to design new selective agonist ligands with high affinity for any AMPA/kainate
      receptor.

PMID- 14637200
TI  - Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo
      immunological effects.
AB  - trans-Resveratrol is a dietary polyphenolic compound present in grapes, which has
      been shown to exhibit strong anti-inflammatory, antioxidant, and chemopreventive
      activities. In this study we have compared the in vitro and in vivo effects of
      resveratrol on the development of various cell-mediated immune responses,
      including mitogen/antigen-induced T cell proliferation, induction of cytotoxic T
      lymphocytes (CTLs), interleukin-2 (IL-2) induced lymphokine activated killer
      cells, and cytokine production. We found significant suppression (>90%) of the
      mitogen/antigen-induced T cell proliferation and development of allo-antigen
      specific CTLs in vitro with resveratrol at a concentration of 25 microM.
      Intragastric administration of resveratrol (2 mg daily) to mice for 4 weeks
      showed no effect on age-related gain in body weight, peripheral blood cell counts
      (WBC, RBC, or platelets), or the cellularity of bone marrow or spleen. The CD4(+)
      and CD8(+) T cells in spleen or colony-forming units-total in the marrow also
      remained unaffected by treatment with resveratrol. Spleen cells, which were
      stimulated in vitro after being removed from mice which had been administered
      resveratrol for 2 or 4 weeks, showed no significant change in IL-2 or
      concanavalin A induced proliferation of T cells or production of IL-2 induced
      lymphokine activated killer cells. Further, the production of in interferon-gamma
      and IL-12 was not affected by administration of resveratrol, but production of
      tumor necrosis factor-alpha was reduced. Even when conducted entirely in vivo,
      treatment with resveratrol was found to only marginally reduce allo-antigen
      induced T cell proliferation and the generation of CTLs in the draining lymph
      nodes. Thus, even though resveratrol strongly inhibits T cell proliferation and
      production of cytolytic cells in vitro, oral administration of resveratrol for 4
      weeks does not induce hematologic or hematopoietic toxicity, and only marginally
      reduces the T cell-mediated immune responses.

PMID- 14637201
TI  - Aminoguanidine downregulates expression of cytokine-induced Fas and inducible
      nitric oxide synthase but not cytokine-enhanced surface antigens of rat islet
      cells.
AB  - Autoimmune beta-cell destruction occurs directly by cell-mediated cytotoxicity or
      indirectly by cytokines released from infiltrating lymphocytes. Cytokines (IL
      1beta/IFN-gamma) modify or induce expression of MHC antigens and ICAM-1 on beta
      cells which can lead to an improved binding of T-lymphocytes to beta-cells and
      finally to an enhanced cell-mediated cytotoxicity. Cytokines also induce Fas
      expression and inducible nitric oxide synthase (iNOS) causing generation of
      nitric oxide (NO) which is toxic for beta-cells. The iNOS inhibitor
      aminoguanidine (AG) delays diabetes onset, but does not reduce diabetes
      incidence. We wanted to know whether AG inhibits cytokine-induced expression of
      Fas, MHC antigens and ICAM-1 on beta-cells of LEW.1W and BB/OK rat islets after
      culture with IL-1beta/IFN-gamma. NO was completely inhibited by 5.0 mmol/L AG
      while 0.5 mmol/L had no inhibitory effect. AG downregulated Fas-expression on the
      surface of beta-cells. Cytokine-induced/enhanced expression of MHC class-II and
      ICAM-1 was not affected by any AG concentration. AG syngergistically increased
      cytokine-induced enhancement of MHC class-I antigen density. AG possibly blocks
      the indirect pathway of beta-cell damage in vivo due to inhibition of Fas and
      iNOS and improves direct cell-mediated cytotoxicity due to drastic increased MHC
      class-I expression. Inhibition of only one pathway of beta-cell destruction is
      not sufficient to prevent diabetes.

PMID- 14637203
TI  - Conceptual issues in theorising anorexia nervosa: mere matters of semantics?

PMID- 14637204
TI  - Rethinking the anorexic body: how English law and psychiatry 'think'.

PMID- 14637205
TI  - Involuntary treatment of anorexia nervosa.

PMID- 14637206
TI  - Control and compulsory treatment in anorexia nervosa: the views of patients and
      parents.

PMID- 14637207
TI  - Institutional options in management of coercion in anorexia treatment: the
      antipodean experiment?

PMID- 14637208
TI  - End stage anorexia: criteria for competence to refuse treatment.

PMID- 14637210
TI  - Treatment coercion: listening carefully to client and clinician experiences.

PMID- 14637209
TI  - Competence to refuse treatment in anorexia nervosa.

PMID- 14637211
TI  - Fraudulent misrepresentation and eating disorder.

PMID- 14637212
TI  - Clinical decision analysis and anorexia nervosa.

PMID- 14637213
TI  - The effect of voluntary exercise exposure on histological and neurobehavioral
      outcomes after ischemic brain injury in the rat.
AB  - Physical activity can induce neuroplastic adaptations and improve outcomes after
      cerebral injury. To determine if these outcomes are dependent on the type and
      timing of physical rehabilitation and the particular outcome/endpoint being
      tested, we evaluated the effect of voluntary exercise exposure beginning 24 h
      after cerebral ischemic injury on behavioral, physiological, and histological
      outcomes. In an observer-blinded fashion, Sprague-Dawley (300 g) male rats were
      allocated to three groups [sham-exercise (SHAM), stroke-exercise (SE), stroke-no
      exercise (SNE)] before a 1-h right middle cerebral artery occlusion (MCAo).
      Running wheels were used for voluntary exercise. A significant difference was
      found at 1 week post-infarction between the SNE and SE, with SNE showing worst
      neurological scores and higher number of foot faults. In addition, nearly 20%
      more of the SE animals regained their pre-MCAo weight by 7 days. These
      differences were not as evident at 2 weeks. No differences were found between the
      three groups in the paw preference test, wheel activity, and body temperature, as
      well as between SNE and SE with regards to infarct or hemispheric volumes, body
      weight, synaptophysin staining, and electroencephalography (EEG) testing. Within
      group comparisons showed no relationships between infarct volume and foot faults,
      neurological scores, or exercise level. We conclude that (1) unlike behavioral
      outcomes, physiological and histological outcomes may not be influenced by the
      introduction of voluntary exercise once lesion maturation has occurred at 24 h,
      and (2) repetitive outcomes testing can obscure findings in rat models of
      cerebral ischemic injury.

PMID- 14637214
TI  - Zymosan: induction of sickness behavior and interaction with lipopolysaccharide.
AB  - The yeast particulate zymosan (Zy) activates innate immune system cells and
      induces cytokine secretion. There is also evidence that Zy can affect biologic
      responses to bacterial lipopolysaccharide (LPS) and that the pathways by which
      these two agents act upon immune cells are only partially distinct. The present
      experiments assessed the ability of Zy to elicit CNS-mediated sickness symptoms
      and to alter their responses to LPS. In Experiment 1, Zy induced elements of the
      sickness behavior syndrome dose-responsively in Long-Evans rats, as indicated by
      reductions in consumption of a highly palatable bait and in body temperature. In
      Experiment 2, Zy exerted a priming effect, sensitizing animals to subsequent LPS
      as measured by reductions in bait consumption, 24-h laboratory chow intake, and
      body temperature. Experiment 3 failed to provide evidence for LPS-to-Zy cross
      tolerance but did indicate that the administration of Zy disrupts previously
      acquired LPS tolerance. These results suggest that the specifics of exposure to
      microbially derived innate immune activators have to be taken into account in
      investigating the biologic bases of sickness behaviors and developing models of
      coinfection.

PMID- 14637215
TI  - Differences in the endocrine and behavioral profiles during the peripartum period
      in macaques.
AB  - The present investigation aims to assess the changes in both social interaction
      and sex steroids excreted in feces of group-living Japanese macaques and rhesus
      monkeys. By comparing profiles of estrone conjugates (E1C) and pregnanediol
      glucuronide (PdG) with the behavioral propensities of two closely related species
      living in similar environments, we could test the hypothesis that the social
      behavior of pregnant females shows significant hormonally mediated changes during
      the late prepartum and early postpartum period. We found a general tendency to
      withdraw from social life across pregnancy in both species. These behavioral
      changes were paralleled by endocrine profiles showing a slight prepartum increase
      in E1C during the last week in the rhesus group, whereas the increase was more
      marked and continuous in the Japanese macaque group. PdG increased slightly in
      rhesus macaques, whereas in Japanese macaques the fluctuations were not
      significant. Postpartum, both hormones dropped to low levels in both species,
      with no significant variation therein. Consequent to these changes, the E1C/PdG
      ratio increased significantly in late pregnancy only in the Japanese macaque
      group. Overall, these results show significant differences in the social behavior
      and endocrine profiles of two closely related species, thus complementing
      previous findings and indicating species-specific characteristics of the
      association between changes in affiliative behaviors and hormonal fluctuations.
      In particular, the shift between grooming performed and self-grooming, which
      showed the closest association with variations in the E1C/PdG ratio, could
      represent a reliable indicator of the change in the internal status of pregnant
      females, and is probably functional to infant survival.

PMID- 14637216
TI  - Diurnal rhythm disorder of behavioral activity in SAMP1 mice is partially
      normalized by spontaneous wheel running.
AB  - We examined the diurnal rhythms of food and water intake, spontaneous wheel
      running (SWR), and spontaneous motor activity (SMA) in the SAMP1 strain, a mouse
      model of accelerated senescence. Without SWR exercise, food, and water intake in
      the SAMP1 mice was significantly higher during the light (L)-phase of the light
      darkness (LD) cycle than in the control SAMR1 strain. Additionally, SWR and SMA
      activity rhythms were split in SAMP1 mice, as demonstrated by the appearance of a
      secondary peak starting from the end of the dark (D)-phase. SWR exercise
      significantly increased the percentages of nocturnal food and water intake and
      SMA in the SAMP1 mice, although food and water intake did not reach the level of
      control SAMR1 mice. Thus, the disordered diurnal rhythms in SAMP1 mice can be
      normalized, even if only partially, by SWR exercise.

PMID- 14637217
TI  - Sex differences in serotonergic activity in dorsal and median raphe nucleus.
AB  - There is evidence on the existence of sex differences in the serotonergic system
      of the raphe. This study examines sex-based differences in serotonergic activity
      in the dorsal (DRN) and median (MRN) raphe nucleus; two structures that have
      consistently been implicated in the brain circuitry associated with fear and
      anxiety reactions. We also analyzed the effects of the elevated plus-maze (EPM)
      test, which allows the measuring of behavioral reactions to stress on rats
      produced by fear to height and open spaces on such sex differences. The present
      study was carried out on 70- to 80-day-old rats exposed or not to the EPM test.
      Immediately after the test, or 10-12 days later, groups of animals were
      sacrificed to measure serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA)
      concentration in the DRN and MRN, to calculate the serotonergic activity ([5
      HIAA]/[5-HT]). Serotonergic activity in the female's DRN was consistently higher
      than in male's DRN. Such differences were not observed in the MRN. While exposed
      to the EPM test, female rats display more aversive responses than males, only
      during the day of diestrus 1. After the EPM test, serotonergic activity decreased
      in the female's DRN and in the male's MRN, both immediately and 10-12 days later.
      The sex-based differences in fear/anxiety reported in this study could be linked
      to the observed decrease in serotonergic activity in the DRN of female rats after
      the EPM test.

PMID- 14637218
TI  - The effect of apomorphine on genital reflexes in male rats deprived of
      paradoxical sleep.
AB  - Drugs that stimulate dopamine (DA) systems can stimulate sexual arousal in male
      rats and humans, and previous work has shown that cocaine enhances genital
      reflexes [penile erection (PE) and ejaculation (EJ)] in rats deprived of
      paradoxical sleep (PS). The present study sought to expand the latter finding by
      assessing the effects of DA receptor agonist apomorphine in sleep-deprived rats.
      Apomorphine in doses ranging from 10 to 240 microg/kg was administered
      intraperitoneally to rats that had been deprived of sleep for 4 days and to
      normal controls, and the incidence of PEs and EJs was measured for 60 min. Sleep
      deprivation alone induced PE and this effect was potentiated by apomorphine, with
      maximal effects occurring with the 120 microg/kg dose; results for this dose
      group differed from those of PSD groups treated with 0, 10, 20, 40, 80, and 240
      microg/kg of apomorphine. Sleep deprivation alone also induced spontaneous EJ,
      but this response was not potentiated by apomorphine in the dose range tested. We
      suggest that the potentiating effects of apomorphine on PE are likely due to PSD
      induced DA receptor supersensitivity.

PMID- 14637219
TI  - Adult cortisol response to immature offspring play in captive squirrel monkeys.
AB  - Variable environmental and social conditions influence hypothalamic-pituitary
      adrenal activity in captive animals. Socially separated and individually housed
      animals generally experience increased cortisol secretion compared to animals
      housed with conspecifics, and social companionship can buffer the stress response
      when exposed to challenges such as introduction to novel environments.
      Nevertheless, the presence of conspecifics may also be the cause of stress
      because social dynamics impact individuals. Squirrel monkeys (Saimiri spp.)
      readily form same-sex affiliative social relationships, but in captivity, the
      presence of immature offspring severely disrupts affiliative associations among
      adults. We examined behavioral and physiological effects of the presence of
      immature offspring on adults by comparing two groups of adults with immature
      offspring to an all-adult group. We conducted behavioral observations and
      collected urine from adult members, and urine was assayed for cortisol at the
      Wisconsin National Primate Research Center. Adults in groups with immature
      offspring received an average of 18 play attempts per hour from the offspring,
      experienced a fivefold decrease in adult affiliation, and showed higher urinary
      cortisol levels compared to the all-adult group. A principal components analysis
      showed that adults characterized by receiving play attempts, rejecting play
      attempts, and lacking affiliative contact with other adults showed the highest
      mean urinary cortisol levels. Further analyses demonstrated that the persistent
      play attempts by immature offspring, not the resulting lack of adult huddling,
      were primarily responsible for the observed increase in urinary cortisol levels.
      Taken together, these data suggest that the disruptive effect of immature
      offspring produces a chronic cortisol increase in captive adult squirrel monkeys.

PMID- 14637220
TI  - Conspecific odor investigation by gray short-tailed opossums (Monodelphis
      domestica).
AB  - Gray short-tailed opossums (Monodelphis domestica) are small marsupials, which
      have recently become the subjects of numerous laboratory investigations. While
      these opossums have well-developed olfactory systems and complex scent-marking
      behaviors, the significance of their use of odors in conspecific communication is
      still poorly understood. Investigation of body odors by male and female opossums
      was examined in the present study. Males investigated flank and urine odors of
      nonestrous adult females significantly more than controls, but not urine from
      sexually inexperienced juvenile females or urine of females at cytological
      estrus. Since in this species females have an induced estrus, it would be
      advantageous for males to investigate and follow the odors of urine of diestrous
      females, which become receptive in proximity to males. Female opossums
      investigated odors of male mandibles and suprasternal glands significantly more
      than controls but not odors of male urine. We suggest that the use of glandular
      secretions is more common and more effective than urine for intraspecific
      communication between gray short-tailed opossums: In the semiarid conditions
      inhabited by the opossums, glandular secretions are less volatile and are
      effective for longer periods than urine and would be of greater value in
      intraspecific communication if, as suggested in the literature, these opossums
      are nomadic and meet one another infrequently.

PMID- 14637221
TI  - Oxytocin antagonism alters rat dams' oral grooming and upright posturing over
      pups.
AB  - Studies involving intracerebral administration of antiserum or antagonists have
      demonstrated that central oxytocin (OT) plays a prominent role in initiating but
      not maintaining postpartum maternal behavior in rats. There has been little
      investigation, however, of OT's influence on the levels of maternal behavior
      exhibited during the maintenance phase. We measured rat dam behavior during the
      105-min observation periods preceding and beginning 2 h after
      intracerebroventricular infusion of the selective OT antagonist (OTA) (1 microg),
      or normal saline (NS) vehicle (5 microl) on postpartum days 2-3 and 6-7. Compared
      to NS, OTA significantly decreased pup licking as a proportion of dams' total
      oral grooming, increased self-grooming, decreased the frequency of elevated
      upright posture over pups and increased the frequency of lying prone on pups.
      Quiescent, kyphotic nursing was also significantly lower in OTA-treated dams.
      Other components of maternal behavior were not significantly affected by OTA or
      NS treatment. These findings suggest that central OT may shift the focus of the
      dams' oral grooming from self to pups and may also facilitate elevation of dams'
      upright posture over pups. Acute stress responses, maternal behavior and central
      OT receptor binding in adult rats have been linked to the amount of maternal
      licking and arched back, upright nursing received during infancy. OT activity in
      dams' brains may influence these developmental outcomes in their offspring by
      selectively regulating their pup licking and crouching posture.

PMID- 14637222
TI  - Effect of sibutramine on macronutrient selection in male and female rats.
AB  - Sibutramine, a serotonin-noradrenaline reuptake inhibitor (SNRI), has been shown
      to be a safe and effective weight-loss drug. The purpose of the present study was
      to examine whether sibutramine has an effect on macronutrient selection in both
      female and male rats in addition to total food intake. Wistar rats of both sexes
      were divided into three groups, and each group was offered a different set of
      three sensorily contrasting macronutrient-specific diets, each set including
      carbohydrate-, protein-, and fat-rich diets. Sibutramine (10 mg/kg) was shown to
      consistently decrease carbohydrate and fat intake at all data points regardless
      of gender and diet. Intake of carbohydrate differed between male and female rats
      at 2 h post administration with 2.5 and 5 mg/kg of sibutramine. The effect of
      sibutramine on protein intake was diet- and gender-specific. All doses of
      sibutramine decreased total food intake regardless of gender and diet group
      beginning at 6 h post administration. In conclusion, sibutramine affected
      macronutrient selection and emphasis on dietary recommendations, as well as
      appropriate dosage according to gender should be considered during therapy.

PMID- 14637223
TI  - Independent effects of diet palatability and fat content on bout size and daily
      intake in rats.
AB  - Although considerable evidence attests to the hyperphagic effects of high-fat
      (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density,
      and postingestive effects) which promote overeating is still unclear. The present
      studies investigated the independent effects of diet palatability and
      macronutrient composition on intake using the self-regulated intragastric
      infusion paradigm. In Experiment 1, rats were infused with either HF or high
      carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable
      saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily
      intake than HC; lick pattern analysis revealed that HF produced larger but not
      more frequent bouts. Test solution was not related to intake, possibly due to the
      relatively modest palatability manipulation. Experiment 2 provided a more
      sensitive test: The palatability manipulation was strengthened and diet infusion
      made optional by provision of chow. HF again elicited larger bout size and total
      daily intake (diet+chow) than HC. Rats given the more palatable solution
      significantly increased intake (via larger bouts) and thus the amount of diet
      infused, but chow intake decreased such that total kilocalorie intake was not
      significantly related to solution palatability. The reliable observation that HF
      promoted larger bout size and greater total kilocalorie intake than HC provides
      additional evidence that fat sends weaker feedback signals relevant to controls
      of both satiation (suppression of ongoing eating, behaviorally manifest in meal
      size) and satiety (suppression of subsequent intake, reflected in total daily
      intake).

PMID- 14637224
TI  - Environmental enrichment: effects on stereotyped behavior and neurotrophin
      levels.
AB  - The present study evaluated whether environmental enrichment-related effects on
      the development of stereotyped behavior in deer mice were associated with
      alterations in neurotrophin levels. Deer mice were reared in enriched or standard
      cage conditions for 60 days. The mice were then tested in automated photocell
      detectors and classified as either stereotypic or nonstereotypic. This testing
      paradigm yielded four behaviorally distinct groups: enriched stereotypic,
      enriched nonstereotypic, standard cage stereotypic, and standard cage
      nonstereotypic. The motor cortex, striatum, and hippocampus were dissected, and
      the levels of brain-derived neurotrophin factor (BDNF) and nerve growth factor
      (NGF) in each brain region were analyzed using Promega ELISA kits. There were no
      differences in either NGF or BDNF in either the motor cortex or the hippocampus.
      In the striatum, the enriched nonstereotypic mice exhibited significantly more
      BDNF than the enriched stereotypic, the standard cage nonstereotypic, or the
      standard cage stereotypic mice. There were no differences in NGF in the striatum.
      These results provide evidence that the enrichment-related prevention of
      stereotyped behavior in deer mice is associated with increased BDNF in the
      striatum.

PMID- 14637225
TI  - Study on the development of sperm motility and social dominance of male mice.
AB  - It has been shown that sperm motility and other parameters related to the
      reproductive activity varied depending on the social status of male mice. In
      order to clarify whether such variation is derived from inborn difference or
      depends on any conditions during maturation, we investigated developmental change
      of sperm motility, reproductive organs, and body size of ddY male mice. We also
      investigated how the establishment of social dominance of male mice during
      maturation was correlated with sperm motility. It was found that sperm motility
      was significantly higher during puberty than in adulthood, although there already
      existed relatively large statistical variance. The correlation between sperm
      motility and the social status was revealed to start after 10 weeks of age. It
      was suggested that a certain inborn difference of sperm motility became enlarged
      due to environmental factors experienced by male mice during maturation.

PMID- 14637226
TI  - Development of, and recovery from, activity-based anorexia in female rats.
AB  - Activity-based anorexia occurs in rats maintained on a restricted-feeding
      schedule while given free access to running wheels. These conditions induce high
      levels of wheel running and rapid weight loss. Although this procedure was
      developed as an animal model of anorexia nervosa, it has been studied primarily
      in male rats. Our goal was to examine the development of, and recovery from,
      activity-based anorexia in female rats. Food intake, wheel running, body weight,
      and phase of the estrous cycle were monitored daily prior to, during, and after a
      period of restricted feeding in which access to food was limited to 2 h/day. Food
      intake, body weight, and estrous cyclicity were also monitored in a control group
      housed without access to running wheels. Prior to food restriction, rats with
      wheels displayed high levels of wheel running and consumed more food than rats
      without wheels. Despite that both groups consumed similar amounts of food during
      the restricted-feeding phase, only rats with wheels developed symptoms of
      activity-based anorexia, including increased wheel running, rapid weight loss,
      and disruptions in estrous cyclicity. Recovery from activity-based anorexia was
      associated with hypoactivity and hyperphagia. Resumption of estrous cycles
      occurred when the weight lost during food restriction was regained. Hyperphagia,
      but not hypoactivity, was maintained following resumption of estrous cycles;
      however, this hyperphagia was limited to nonestrous phases. Our findings suggest
      that recovery from activity-based anorexia is mediated primarily by an increase
      in orexigenic signaling that promotes pronounced hyperphagia, and that the
      increase in satiogenic signaling during estrus abolishes this compensatory
      hyperphagia.

PMID- 14637227
TI  - Hypovolemia stimulates intraoral intake of water and NaCl solution in intact rats
      but not in chronic decerebrate rats.
AB  - This experiment tested the hypothesis that afferent signals from cardiac
      baroreceptors to the caudal brain stem are integrated by hindbrain systems to
      control ingestive behavior in response to plasma volume deficits in rats. A
      supracollicular transection was made which should not interfere with the neural
      signal of volume depletion to the hindbrain. Decerebrate (n=5) and control rats
      (n=7) were given subcutaneous injections of 30% polyethylene glycol (PEG) to
      induce hypovolemia or of isotonic saline as a control. Four hours after the
      injection, either water or 0.1 M NaCl was administered through an intraoral
      cannula, and intakes were measured. Decerebrate rats did not ingest significantly
      more water or saline after PEG treatment than after the control treatment,
      whereas control rats ingested both fluids in significantly larger volumes after
      PEG treatment. In another test using the same animals, heart rate was monitored
      after intravenous injections of phenylephrine (to raise blood pressure) and
      nitroprusside (to lower it). Similar reflexive changes in heart rate were
      observed in control and decerebrate rats, showing that baroreflex function was
      not impaired by decerebration. These results indicate that baroafferent signals
      are processed at multiple levels of the neuraxis, with hindbrain systems
      mediating autonomic cardiovascular reflexes in response to changes in blood
      pressure, and midbrain or forebrain systems mediating behavioral responses
      associated with thirst.

PMID- 14637228
TI  - Lingual tactile acuity, taste perception, and the density and diameter of
      fungiform papillae in female subjects.
AB  - A growing body of evidence suggests that individuals who differ in taste
      perception differ in lingual tactile perception. To address this issue, spatial
      resolution acuity was estimated for 83 young adult females (52 Asians and 31
      Caucasians) by their ability to examine with the tongue and identify embossed
      letters of the alphabet. Ratings of the magnitude of the bitterness of 0.0032M 6
      n-propylthiouracil (PROP) were obtained to characterize subjects' taste
      perception. The density and diameter of fungiform papillae on the anterior
      tongues of the Asian subjects were measured also. Subjects who rated the
      bitterness of PROP as very or intensely strong (supertasters) were found to be
      about 25% more tactually acute than subjects who rated the bitterness as moderate
      to strong (medium tasters) and twice as acute as subjects who rated it as
      nondetectable or weak (non-tasters; P<.0001): The threshold heights for letter
      recognition averaged 2.8, 3.5 and 5.4 mm, respectively, for the Asian subjects
      and 2.6, 3.2, and 5.1 mm for the Caucasian subjects. The thresholds correlated
      highly with subjects' ratings of bitterness (rho=-0.84, P<.0001), and for the
      Asian subjects with the density (rho=-0.84, P<.0001) and diameter (rho=0.66,
      P<.0001) of fungiform papillae. Mean densities varied from 54.4 cm(-2) (non
      tasters) to 106.5 cm(-2) (medium tasters) to 143.7 cm(-2) (supertasters;
      P<.0001). These findings confirm that individuals who differ in taste (PROP)
      sensitivity also differ in lingual tactile acuity. Tactile and taste
      sensitivities covary and reflect individual differences in the density and
      diameter of fungiform papillae on the anterior tongue.

PMID- 14637229
TI  - Repeated social stress and the development of agonistic behavior: individual
      differences in coping responses in male golden hamsters.
AB  - In male golden hamsters, repeated social subjugation during puberty accelerates
      the development of adult aggressive behavior and enhances its intensity in the
      presence of smaller individuals. The current study is focused on the
      characterization of the hormonal and behavioral responses to social subjugation
      during puberty. Subjugation consisted of daily exposure to an aggressive adult
      for 20-min periods from postnatal day 28 (P-28) to P-42, while controls were
      placed into an empty clean cage. Plasma cortisol levels were measured prior to or
      immediately after treatment on P-28 and P-42. On P-28, exposure to an aggressive
      adult or a clean and empty cage caused an increase in plasma cortisol levels.
      However, only social subjugation resulted in elevated cortisol levels on P-42,
      showing that juvenile hamsters habituate to an unfamiliar environment but not to
      social subjugation. In addition, we found a relationship between the frequency of
      submissive responses during social subjugation and the development of aggressive
      behavior. The transition from play fighting to adult aggression was most
      accelerated in the least submissive animals. These data show that behavioral
      response to social subjugation determines the development of aggressive behavior
      in golden hamsters. Our data also suggest that submissive behavior is a form of
      coping that attenuates the behavioral consequences of social subjugation in male
      golden hamsters.

PMID- 14637230
TI  - Long-term recordings from afferent taste fibers.
AB  - The receptor cells of taste buds have a life span of about 10 days but it is not
      known if response characteristics of these receptors alter during the turnover
      cycle. To examine taste cell responses over time, a micromachined polyimide sieve
      electrode array was implanted between the cut ends of the rat chorda tympani
      nerve, which then regenerated through the electrode array. Long-term stable
      recordings from regenerated single afferent fibers innervating taste buds were
      possible using this technique for up to 21 days. Responses to taste stimuli
      recorded from the same fiber changed with time. The changes occurred in both the
      magnitude of response and the relative response profiles to four chemical
      stimuli, NaCl, sucrose, HCl, and quinine HCl. These changes in response
      characteristics were hypothesized to result from changes in the taste receptor
      cells as the receptor cells turnover in the taste buds.

PMID- 14637231
TI  - Novel-object place conditioning in adolescent and adult male and female rats:
      effects of social isolation.
AB  - Elevated levels of novelty seeking are often seen during adolescence. Recent
      studies using a conditioned place preference (CPP) paradigm have shown that
      novelty may be rewarding for adult rats. The present study explored the impact of
      age, sex, and isolation stress on novelty seeking and novelty reward by assessing
      novel object-induced CPP in adolescent and adult male and female Sprague-Dawley
      rats housed either socially or in isolation. Responding to the novel objects
      during conditioning was higher in adolescent animals than adults, and was
      suppressed by social isolation only in adulthood, particularly among males. Novel
      object CPP was strong among adolescent males, whereas only socially isolated
      adult males demonstrated preference for the compartment paired with the novel
      objects. This age difference was not evident in females, with both adolescent and
      adult group-housed females, but not their isolated counterparts, showing novel
      object place conditioning. These dissociations between novelty-directed behaviors
      during conditioning and novelty reward in the CPP paradigm support the suggestion
      that mechanisms underlying novelty seeking are separable from those involved in
      the rewarding effects of novelty. High levels of novelty seeking demonstrated by
      adolescents do not necessarily predict high rewarding properties of novelty, with
      the latter also being influenced by environmental and gender-related factors.

PMID- 14637232
TI  - Fenfluramine challenge, self-injurious behavior, and aggression in rhesus
      monkeys.
AB  - Self-injurious behavior (SIB) and aggression have been linked to reduced
      serotonergic (5-HT) functioning in both humans and nonhuman primates. The present
      study examined serum prolactin and cortisol responses to the 5-HT releasing agent
      D,L-fenfluramine (FEN) in 24 individually housed rhesus monkeys (Macaca mulatta),
      15 of which carried a veterinary record of self-wounding (SW). Subjects received
      two doses of FEN, 4 and 2 mg/kg, separated by an interval of at least 2 months.
      For control purposes, monkeys were given an intramuscular saline injection 1 week
      prior to each FEN challenge. The relationship between the hormonal responses to
      FEN, wounding history, the rates of self-directed biting and aggression were
      determined for each animal based on 100 five-minute observations conducted over a
      period of 12 months surrounding the challenge procedures. Prolactin and cortisol
      responses to FEN were unrelated either to wounding history or to rates of self
      directed biting. However, there were significant inverse correlations between
      levels of aggression and the prolactin response to both doses of FEN. The present
      findings provide no evidence for reduced 5-HT system function in rhesus monkeys
      with SIB under the present challenge conditions. However, the results are
      consistent with a previously reported inverse relationship between serotonergic
      activity and aggression. Moreover, a dose-dependent response to FEN was observed
      only for prolactin, suggesting that this variable is more appropriate than
      cortisol as an endpoint for FEN challenge in monkeys.

PMID- 14637233
TI  - Motor coordination in mice with hotfoot, Lurcher, and double mutations of the
      Grid2 gene encoding the delta-2 excitatory amino acid receptor.
AB  - Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic
      arborizations of Purkinje cells. These mutants were compared in a series of motor
      coordination tests requiring balance and equilibrium to nonataxic controls
      (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation.
      The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on
      stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc)
      did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation
      in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary
      beam, unsteady platform, and rotorod tests. These results indicate a deleterious
      effect of the Lc mutation on Grid2-deficient mice.

PMID- 14637234
TI  - Preferences towards novel foods in Cebus apella: the role of nutrients and social
      influences.
AB  - Information on the process of preference acquisition towards novel foods in
      nonhuman primates is lacking. This study aims to assess (1) whether nutrient and
      energy contents affect preferences towards novel foods encountered repeatedly by
      individuals when alone, (2) whether these preferences change after additional
      encounters with the novel foods, and (3) if the change is sensitive to social
      influences. We presented seven novel foods to 26 socially housed tufted
      capuchins. In Phase 1, each subject was presented individually with the 21
      possible binary combinations of the seven novel foods. Afterwards, during
      treatment, 13 subjects received the novel foods ad libitum with their group
      members (social condition) and 13 subjects received the foods individually
      (individual condition); subjects assigned to the individual and social conditions
      had shown similar food preferences in Phase 1. Finally, in Phase 2, each subject
      was presented again with 21 binary choices between each of the novel foods. In
      Phases 1 and 2, the number of times each food was chosen differed among foods. In
      Phase 1, food preference correlated positively with glucose and fructose and
      negatively with total fiber content. In Phase 2, irrespective of social or
      individual prior experience in the treatment condition, food preference changed
      and became correlated with total energy content. Our results broaden the findings
      already available for familiar foods by demonstrating that individual experience
      based on the feedback obtained from novel foods guides the establishment of
      preferences towards them. Moreover, individual experience is sufficient to
      determine food preferences similar to those individuals may acquire when together
      with group members eating the same foods.

PMID- 14637235
TI  - Importance of fighting in the immune effects of social defeat.
AB  - Social defeat involves a clear physical component in the form of fight-induced
      injuries. The impact of body injuries on the immune response is not yet well
      known. In this study we compared the endocrine and immune responses to two types
      of social defeat in mice, one limiting the occurrence of skin injuries (mild
      social stress, MSS), and the other not (social disruption stress, SDR). In the
      two situations, six defeats were applied within 1 week. Plasma corticosterone and
      IL-6 levels were measured in blood samples taken after social defeat. Reactivity
      to LPS and sensitivity to corticosterone (CS) of spleen cells was assessed by
      measuring the in vitro production of cytokines (IL-6, IFN-gamma and IL-10) in
      response to LPS under a range of increasing concentrations of CS. The two types
      of stressors induced a similar plasma corticosterone response, but SDR mice
      showed significantly higher plasma IL-6 than MSS mice. Splenocytes from SDR but
      not from MSS mice produced more IL-6 and IL-10 in response to LPS and presented
      an altered responsiveness to CS in comparison to control mice. We conclude that
      the procedure involving fights and skin injuries was able to modulate the immune
      response in the spleen, whereas the procedure preventing the occurrence of fights
      did not. The increased immune reactivity observed in the fight-associated
      procedure could result from either a stronger psychological stress or a direct
      immune activation through the wounds.

PMID- 14637236
TI  - Postnatal weight gain inhibition does not account for neurobehavioral
      consequences of neonatal Borna disease virus infection.
AB  - Neonatal Borna disease virus (BDV) infection of the rat's brain produces
      neurodevelopmental damage similar to some pathological and clinical features of
      human developmental disorders, e.g., autism and schizophrenia. Since BDV-infected
      rats exhibited an inhibition of postnatal weight gain, the present study sought
      to evaluate a contribution of nutritional status to virus-induced
      neurodevelopmental injury. We compared neuroanatomical, neurochemical, and
      behavioral alterations following neonatal BDV infection and rearing in the
      oversized litters in Fischer344 rats on postnatal day (PND) 26. Despite a
      comparable weight gain inhibition, different patterns of brain pathology,
      alterations in brain monoamine systems, and behavioral deficits were observed in
      the BDV-infected rats compared to the malnourished rats. While no appreciable
      cell injury was noted in the brains of the malnourished rats, a significant loss
      of Purkinje cells (PC) and early signs of degeneration of the hippocampal dentate
      gyrus were found in the BDV-infected rats. Both neonatal BDV infection and
      postnatal malnourishment increased tissue concentrations of serotonin [5
      hydroxytryptamine (5-HT)] in the hippocampus. In contrast, increased turnover of
      5-HT in the cortex and hippocampus and elevated turnover of dopamine (DA) in the
      striatum were found in the malnourished rats only, suggesting that different
      pathogenic mechanisms might underlie monoamine disturbances in virus-infected and
      malnourished rats. The observed dissimilar neuroanatomical and neurochemical
      abnormalities might explain the different responses to novelty in the BDV
      infected and malnourished rats. Compared to the control rats, the BDV-infected
      rats exhibited novelty-induced hyperactivity, while no differences in locomotion
      were noted between the control and malnourished rats. Taken together, the present
      data indicate that virus-associated inhibition of postnatal weight gain is
      unlikely to account for the major BDV-associated neurodevelopmental alterations
      that seem to be due to specific effects of neonatal BDV infection.

PMID- 14637237
TI  - Emotions in overweight and normal-weight women immediately after eating foods
      differing in energy.
AB  - Immediate effects of low-, medium-, and high-energy foods on the emotional state
      of normal-weight and overweight women were studied experimentally. Nineteen
      normal-weight (body mass index [BMI]: 19-25 kg/m2) and 19 overweight women (BMI:
      26-40 kg/m2) aged 18-40 years received samples of food that differed in energy
      content (low vs. medium vs. high energy) and rated their emotional state
      immediately after eating. Perceived characteristics of the foods and associations
      elicited by the foods were also obtained. Negative emotions (anger, fear, shame,
      and sadness) and sleepiness increased, while happiness decreased with energy of
      foods. Emotionally negative associations were more frequent, while positive
      emotions were less frequent the higher the energy content of the foods. Sadness,
      shame, fear, and sleepiness after eating high-energy food tended to be more
      intense in overweight women. Additional analyses demonstrated influences of
      eating habits, e.g., disinhibition. The higher the energy content of a food
      stimulus, the more it was viewed as "unhealthy" and "dangerous." It is suggested
      that immediate food-induced changes of emotions can be explained by activation of
      associative emotion networks.

PMID- 14637238
TI  - Food wasting by house mice: variation among individuals, families, and genetic
      lines.
AB  - Under ad libitum conditions, laboratory house mice (Mus domesticus) fragment
      considerable amounts of pelleted food and leave it scattered in their cages. The
      proportion of food thus wasted (in relation to food eaten) varies remarkably
      among individuals, from 2% to 40%, but is highly consistent in consecutive
      trials, even when the mice were moved from 22 to -10 degrees C and food
      consumption doubled. Food wasting did not differ either between the sexes or
      between genetic lines that had been selected (10 generations) for high voluntary
      wheel-running behavior (n=4) and their unselected control lines (n=4). However,
      it varied significantly among replicate lines within the selection groups and
      among families within the lines (coefficient of intraclass correlation for full
      sibs, rhof=0.41 in room temperature trials and rhof=0.34 in cold trials).
      Moreover, the percent of food wasted was negatively correlated with food
      consumption in the cold trials (males: r=-.36, females: r=-.20) and with total
      litter mass at weaning (the litters into which they were born; r=-.24), two
      traits that may affect Darwinian fitness. We conclude that food wastage should
      not be ignored without justification in calculations of food consumption. In
      addition, "table manners" can convey reliable information about family origin of
      an individual and its quality, and therefore could potentially play a role in
      establishment of social status.

PMID- 14637239
TI  - The relative playfulness of juvenile Lewis and Fischer-344 rats.
AB  - The relative playfulness of inbred Lewis and Fischer-344 rats was characterized.
      Fischer rats were consistently less playful than Lewis rats, with rats of this
      strain less likely to initiate playful interactions with either responsive or
      unresponsive partners and also less likely to respond playfully when playful
      solicitations were directed to them. While less playful, Fischer rats were more
      socially inquisitive than Lewis rats when tested with an unresponsive partner,
      suggesting that Fischer rats are less likely to escalate a social encounter into
      a playful one. Strain differences in playful responsiveness were present with or
      without prior social isolation, suggesting that this aspect of play represents a
      relatively stable trait difference. Unlike play responsiveness, strain
      differences in play solicitation were only apparent after a period of social
      isolation. Low levels of play were still present in Fischer rats that had been
      reared by Lewis dams, suggesting a genetic source for the altered play in rats of
      this strain. Further studies of play behavior in Lewis and Fischer rats could
      illuminate relevant neural involvement in rough-and-tumble play and also help
      understand the genetic bases for this complex social behavior.

PMID- 14637240
TI  - Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.
AB  - The effect of kissing on allergen-induced skin wheal responses and plasma
      neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic
      rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients
      with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen
      (JCP). They are all Japanese and they do not kiss habitually. The subject kissed
      freely during 30 min with their lover or spouse alone in a room with closed doors
      while listening to soft music. Before and after kissing, skin prick tests were
      performed using commercial HDM allergen, JCP allergen, as well as histamine and
      control solution, and wheal responses were measured. Simultaneously, plasma
      levels of neurotrophin, including nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured.
      Kissing significantly reduced wheal responses induced by HDM and JCP, but not by
      histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients
      with AR or AD, while it failed to do so in normal subjects. These finding
      indicate that kissing have some implication in the study of neuroimmunology in
      allergic patients.

PMID- 14637241
TI  - Deiodinating activity in the brown adipose tissue of rats following short cold
      exposure after strenuous exercise.
AB  - Interscapular brown adipose tissue (IBAT) activity is controlled by the
      sympathetic nervous system, and factors that influence thermogenesis appear to
      act centrally to modify the sympathetic outflow to IBAT. Cold exposure produces a
      rise in IBAT temperature as a result of the increase in sympathetic outflow to
      IBAT. This is associated with an increased thyroid activity. 3,5,3'
      triiodothyronine (T3) and T4 levels increase during strenuous exercise, and, at
      the end of the exercise bout, a decrease of T3 and T4 levels, with an increase in
      TSH during the following 4-5 days, is seen. We evaluated the effect of strenuous
      exercise on 5'-deiodinase (5'-D) activity in IBAT in normal environmental
      conditions and after short (30 min) cold exposure. 5'-D activity is lower in rats
      at basal condition. Short cold exposure (SCE) increases 5'-D in IBAT both in
      exercising rats and in sedentary rats. However, this increase is lower in
      exercising animals. Strenuous exercise can reduce 5'-D activity in normal
      environmental conditions and after SCE. Probably, other compensatory mechanisms
      of heat production are active in exercising rodents.

PMID- 14637242
TI  - Biochemical and physiological validation of a corticosteroid radioimmunoassay for
      plasma and fecal samples in oldfield mice (Peromyscus polionotus).
AB  - The measurement of fecal steroids provides an increasingly important noninvasive
      technique for assessing reproduction, environmental stress, and aggression in
      populations of captive and free-living animals. In this paper, we validated the
      corticosterone (CORT) 125I-radioimmunoassay (ICN Pharmaceuticals) for plasma and
      fecal samples in a small rodent species, the oldfield mouse (Peromyscus
      polionotus subgriseus). The biochemical validations indicated that the assays
      accurately measured CORT concentrations in the plasma and corticosteroid
      concentrations in the feces. Physiological validation demonstrated that: (1)
      blood samples collected within 3 min of disturbing an animal's cage represented
      "baseline" CORT concentrations, and (2) fecal corticosteroid concentrations
      collected over a 24-h period closely tracked plasma CORT concentrations
      approximately 4 h earlier. These results demonstrate that the plasma CORT and
      fecal corticosteroid assays are sensitive enough to detect biologically
      meaningful alterations in corticosteroid concentrations in oldfield mice.

PMID- 14637244
TI  - Oxidative damage to DNA: formation, measurement and biochemical features.
AB  - Emphasis is placed in the first part of this survey on mechanistic aspects of the
      formation of 8-oxo-7,8-dihydroguanine (8-oxoGua) as the result of exposure to
      z.rad;OH radical, one-electron oxidants and singlet oxygen (1O(2)) oxidation. It
      was found that 8-oxoGua, which is generated by either hydration of the guanine
      radical cation or .OH addition at C8 of the imidazole ring, is a preferential
      target for further reactions with 1O(2) and one-electron oxidants, including the
      highly oxidizing oxyl-type guanine radical. Interestingly, tandem base lesions
      that involve 8-oxoGua and a vicinal formylamine residue were found to be
      generated within DNA as the result of a single .OH radical hit. The likely
      mechanism of formation of the latter lesions involves the transient generation of
      5-(6)-peroxy-6-(5)-hydroxy-5,6-dihydropyrimidyl radicals that may add to the C8
      of a vicinal guanine base before undergoing rearrangement. Another major topic
      which is addressed deals with recent developments in the measurement of oxidative
      base damage to cellular DNA. This was mostly achieved using the accurate and
      highly specific HPLC method coupled with the tandem mass spectrometry detection
      technique. Interestingly, optimized conditions of DNA extraction and subsequent
      work-up allow the accurate measurement of 11 modified nucleosides and bases
      within cellular DNA upon exposure to oxidizing agents including UVA and ionizing
      radiations. Finally, recently available data on the substrate specificity of DNA
      repair enzymes belonging to the base excision and nucleotide excision pathways
      are briefly reviewed. For this purpose modified oligonucleotides in which
      cyclopurine, and cyclopyrimidine nucleosides were site-specifically inserted were
      synthesized.

PMID- 14637245
TI  - Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts
      from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA
      repair and human p53 gene mutation.
AB  - The cyclic 1,N(2)-propanodeoxyguanosine adducts, derived from alpha,beta
      unsaturated aldehydes or enals, including acrolein (Acr), crotonaldehyde (Cro),
      and trans-4-hydroxy-2-nonenal (HNE), have been detected as endogenous DNA lesions
      in rodent and human tissues. Collective evidence has indicated that the oxidative
      metabolism of polyunsaturated fatty acids (PUFAs) is an important pathway for
      endogenous formation of these adducts. In a recent study, we examined the
      specific role of different types of fatty acids, omega-3 and omega-6 PUFAs, in
      the formation of cyclic adducts of Acr, Cro, and HNE. Our studies showed that the
      incubation of deoxyguanosine 5'-monophosphate with omega-3 or omega-6 fatty acids
      under oxidative conditions in the presence of ferrous sulfate yielded different
      amounts of Acr, Cro, and HNE adducts, depending on the types of fatty acids. We
      observed that Acr- and Cro-dG adducts are primarily formed from omega-3, and the
      adducts derived from longer chain enals, such as HNE, were detected exclusively
      from omega-6 fatty acids. Acr adducts are also formed from omega-6 fatty acids,
      but to a lesser extent; the yields of Acr adducts are proportional to the number
      of double bonds present in the PUFAs. Two previously unknown cyclic adducts, one
      from pentenal and the other from heptenal, were detected as products from omega-3
      and omega-6 fatty acids, respectively. Because omega-6 PUFAs are known to be
      involved in the promotion of tumorigenesis, we investigated the role of HNE
      adducts in p53 gene mutation by mapping the HNE binding to the human p53 gene
      with UvrABC nuclease and determined the formation of HNE-dG adducts in the gene.
      The results showed that HNE-dG adducts are preferentially formed in a sequence
      specific manner at the third base of codon 249 in the p53 gene, a mutational
      hotspot in human cancers. The DNA repair study using plasmid DNA containing HNE
      dG adducts as a substrate in HeLa cell extracts showed that HNE adducts are
      readily repaired, and that nucleotide excision repair appears to be a major
      pathway involved. Together, results of these studies provide a better
      understanding of the involvement of different PUFAs in DNA damage and their
      possible roles in tumorigenesis.

PMID- 14637246
TI  - Mutagenicity, toxicity and repair of DNA base damage induced by oxidation.
AB  - Oxidative DNA damage is a major cause of cell death and mutagenesis in all
      aerobic organisms, and several new oxidative base lesions have been identified in
      recent years. Improved chemistry for the synthesis of oligonucleotides with
      modified base residues at defined positions has allowed detailed studies of
      repair, replication, transcription and mutagenesis at specific lesions in vitro
      and in vivo. The aim of this review is to present the structure of all the
      various known oxidised DNA base lesions known to date and to summarise the
      present knowledge about the mutagenic and toxic effects of oxidised base
      modifications and their repair.

PMID- 14637247
TI  - Labile iron pool: the main determinant of cellular response to oxidative stress.
AB  - The trace amounts of "free" iron can catalyse production of a highly toxic
      hydroxyl radical via Fenton/Haber-Weiss reaction cycle. The critical factor
      appears to be the availability and abundance of cellular labile iron pool (LIP)
      that constitutes a crossroad of metabolic pathways of iron-containing compounds
      and is midway between the cellular need of iron, its uptake and storage. To avoid
      an excess of harmful "free" iron, the LIP is kept at the lowest sufficient level
      by transcriptional and posttranscriptional control of the expression of principal
      proteins involved in iron homeostasis. The putative sources of cellular LIP, its
      homeostasis and its role in the cellular response to oxidative stress are
      discussed.

PMID- 14637248
TI  - Quantifying clustered DNA damage induction and repair by gel electrophoresis,
      electronic imaging and number average length analysis.
AB  - Assessing DNA damage induction, repair and consequences of such damages requires
      measurement of specific DNA lesions by methods that are independent of biological
      responses to such lesions. Lesions affecting one DNA strand (altered bases,
      abasic sites, single strand breaks (SSB)) as well as damages affecting both
      strands (clustered damages, double strand breaks) can be quantified by direct
      measurement of DNA using gel electrophoresis, gel imaging and number average
      length analysis. Damage frequencies as low as a few sites per gigabase pair
      (10(9)bp) can be quantified by this approach in about 50ng of non-radioactive
      DNA, and single molecule methods may allow such measurements in DNA from single
      cells. This review presents the theoretical basis, biochemical requirements and
      practical aspects of this approach, and shows examples of their applications in
      identification and quantitation of complex clustered damages.

PMID- 14637249
TI  - Substrate specificities and excision kinetics of DNA glycosylases involved in
      base-excision repair of oxidative DNA damage.
AB  - Reactive oxygen-derived species such as free radicals are formed in living cells
      by normal metabolism and exogenous sources, and cause a variety of types of DNA
      damage such as base and sugar damage, strand breaks and DNA-protein cross-links.
      Living organisms possess repair systems that repair DNA damage. Oxidative DNA
      damage caused by free radicals and other oxidizing agents is mainly repaired by
      base-excision repair (BER), which involves DNA glycosylases in the first step of
      the repair process. These enzymes remove modified bases from DNA by hydrolyzing
      the glycosidic bond between the modified base and the sugar moiety, generating an
      apurinic/apyrimidinic (AP) site. Some also possess AP lyase activity that
      subsequently cleaves DNA at AP sites. Many DNA glycosylases have been discovered
      and isolated, and their reaction mechanisms and substrate specificities have been
      elucidated. Most of the known products of oxidative damage to DNA are substrates
      of DNA glycosylases with broad or narrow substrate specificities. Some possess
      cross-activity and remove both pyrimidine- and purine-derived lesions.
      Overlapping activities between enzymes also exist. Studies of substrate
      specificities have been performed using either oligodeoxynucleotides with a
      single modified base embedded at a specific position or damaged DNA substrates
      containing a multiplicity of pyrimidine- and purine-derived lesions. This paper
      reviews the substrate specificities and excision kinetics of DNA glycosylases
      that have been investigated with the use of gas chromatography/mass spectrometry
      and DNA substrates with multiple lesions.

PMID- 14637250
TI  - 8-Oxoguanine DNA damage: at the crossroad of alternative repair pathways.
AB  - Radical oxygen species (ROS) generate various modified DNA bases. Among them 8
      oxo-7,8-dihydroguanine (8oxoG) is the most abundant and seems to play a major
      role in mutagenesis and in carcinogenesis. 8oxoG is removed from DNA by the
      specific glycosylase OGG1. An additional post-replication repair is needed to
      correct the 8oxoG/A mismatches that are produced by persistent 8oxoG residues.
      This review is focused on the mechanisms of base excision repair (BER) of this
      oxidized base. It is shown that, in vitro, efficient and complete repair of
      8oxoG/C pairs requires a core of four proteins, namely OGG1, APE1, DNA polymerase
      (Pol) beta, and DNA ligase I. Repair occurs predominantly by one nucleotide
      replacement reactions (short-patch BER) and Pol beta is the polymerase of
      election for the resynthesis step. However, alternative mechanisms can act on
      8oxoG residues since Pol beta-null cells are able to repair these lesions.
      8oxoG/A mismatches are repaired by human cell extracts via two BER events which
      occur sequentially on the two strands. The removal of the mismatched adenine is
      followed by preferential insertion of a cytosine leading to the formation of
      8oxoG/C pairs which are then corrected by OGG1-mediated BER. Both repair events
      are inhibited by aphidicolin, suggesting that a replicative DNA polymerase is
      involved in the repair synthesis step. We propose that Pol delta/epsilon-mediated
      BER (long-patch BER) is the mode of repair when lesions persist or are formed at
      replication. Finally, we address the issues of the relative contribution of the
      two BER pathways to oxidative damage repair in vivo and the possible role of BER
      gene variants as cancer susceptibility genes.

PMID- 14637251
TI  - Recognition of damaged DNA by Escherichia coli Fpg protein: insights from
      structural and kinetic data.
AB  - Formamidopyrimidine-DNA glycosylase (Fpg) excises oxidized purines from damaged
      DNA. The recent determination of the three-dimensional structure of the covalent
      complex of DNA with Escherichia coli Fpg, obtained by reducing the Schiff base
      intermediate formed during the reaction [Gilboa et al., J. Biol. Chem. 277 (2002)
      19811] has revealed a number of potential specific and non-specific interactions
      between Fpg and DNA. We analyze the structural data for Fpg in the light of the
      kinetic and thermodynamic data obtained by the method of stepwise increase in
      ligand complexity to estimate relative contributions of individual nucleotide
      units of lesion-containing DNA to its total affinity for this enzyme [Ishchenko
      et al., Biochemistry 41 (2002) 7540]. Stopped-flow kinetic analysis that has
      allowed the dissection of Fpg catalysis in time [Fedorova et al., Biochemistry 41
      (2002) 1520] is also correlated with the structural data.

PMID- 14637252
TI  - Repair of abasic sites in DNA.
AB  - Repair of both normal and reduced AP sites is activated by AP endonuclease, which
      recognizes and cleaves a phosphodiester bond 5' to the AP site. For a short
      period of time an incised AP site is occupied by poly(ADP-ribose) polymerase and
      then DNA polymerase beta adds one nucleotide into the repair gap and
      simultaneously removes the 5'-sugar phosphate. Finally, the DNA ligase III/XRCC1
      complex accomplishes repair by sealing disrupted DNA ends. However, long-patch
      BER pathway, which is involved in the removal of reduced abasic sites, requires
      further DNA synthesis resulting in strand displacement and the generation of a
      damage-containing flap that is later removed by the flap endonuclease. Strand
      displacement DNA synthesis is accomplished by DNA polymerase delta/epsilon and
      DNA ligase I restores DNA integrity. DNA synthesis by DNA polymerase
      delta/epsilon is dependent on proliferating cell nuclear antigen, which also
      stimulates the DNA ligase I and flap endonuclease. These repair events are
      supported by multiple protein-protein interactions.

PMID- 14637253
TI  - DNA N-glycosylase deficient mice: a tale of redundancy.
AB  - The generation of mouse models of base excision repair deficiency has resulted in
      a re-examination of the cellular defence mechanisms that exist to counteract
      oxidative base damage. Contrary to exhibiting various detrimental effects of the
      gene disruption, the different strains of DNA-N-glycosylase deficient mice have
      proved to be remarkably resilient to the loss of the major activities that
      catalyse the removal of oxidised bases from DNA. Indeed, with a few exceptions,
      there is little evidence for the accumulation of oxidised bases in tissues and
      organs of the glycosylase knockout mice, even in older animals. This is highly
      suggestive of hitherto unknown backup mechanisms for dealing with the removal of
      oxidative base damage from genomic DNA. Results from both a genomics-based
      approach and biochemical analyses of cell free extracts from DNA glycosylase
      knockout mice have indicated that this is so and there is increasing evidence of
      several novel DNA glycosylase/AP lyases in mammalian cells that are capable of
      acting on oxidised bases in vitro. This, in parallel with other repair mechanisms
      involving mismatch repair, the Cockayne syndrome B protein and the efficient and
      accurate bypass of replication blocking lesions by a battery of translesion DNA
      polymerases, may explain the lack of severe phenotype observed for the DNA
      glycosylase deficient mice discussed in this article.

PMID- 14637255
TI  - Miscoding properties of 1,N6-ethanoadenine, a DNA adduct derived from reaction
      with the antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea.
AB  - 1,N(6)-Ethanoadenine (EA) is an exocyclic adduct formed from DNA reaction with
      the antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). To understand
      the role of this adduct in the mechanism of mutagenicity or carcinogenicity by
      BCNU, an oligonucleotide with a site-specific EA was synthesized using
      phosphoramidite chemistry. We now report the in vitro miscoding properties of EA
      in translesion DNA synthesis catalyzed by mammalian DNA polymerases (pols) alpha,
      beta, eta and iota. These data were also compared with those obtained for the
      structurally related exocyclic adduct, 1,N(6)-ethenoadenine (epsilonA). Using a
      primer extension assay, both pols alpha and beta were primarily blocked by EA or
      epsilonA with very minor extension. Pol eta, a member of the Y family of
      polymerases, was capable of catalyzing a significant amount of bypass across both
      adducts. Pol eta incorporated all four nucleotides opposite EA and epsilonA, but
      with differential preferences and mainly in an error-prone manner. Human pol
      iota, a paralog of human pol eta, was blocked by both adducts with a very small
      amount of synthesis past epsilonA. It incorporated C and, to a much lesser
      extent, T, opposite either adduct. In addition, the presence of an A adduct, e.g.
      epsilonA, could affect the specificity of pol iota toward the template T
      immediately 3' to the adduct. In conclusion, the four polymerases assayed on
      templates containing an EA or epsilonA showed differential bypass capacity and
      nucleotide incorporation specificity, with the two adducts not completely
      identical in influencing these properties. Although there was a measurable extent
      of error-free nucleotide incorporation, all these polymerases primarily
      misincorporated opposite EA, indicating that the adduct, similar to epsilonA, is
      a miscoding lesion.

PMID- 14637254
TI  - Oxidative DNA damage in cancer patients: a cause or a consequence of the disease
      development?
AB  - A wide variety of oxidative DNA lesions are present in living cells. One of the
      best known lesions of this type is 8-oxoguanine (8-oxoGua) which has been shown
      to have mutagenic properties. An influence of antioxidative vitamins and labile
      iron pool on the background level of 8-oxoGua in cellular DNA is discussed and
      oxidative damage to free nucleotide pool as a possible source of 8-oxo-2'
      deoxyguanosine in DNA and urine is described. An involvement of 8-oxoGua in the
      origin and/or progression of cancer is reviewed. It is concluded that a severe
      oxidative stress manifested as a high level of 8-oxoGua in cellular DNA as well
      as in urine of cancer patients is a consequence of development of many types of
      cancer. Although at present it is impossible to answer directly the question
      concerning involvement of oxidative DNA damage in cancer etiology it is likely
      that oxidative DNA base modifications may serve as a source of mutations that
      initiate carcinogenesis (i.e. they may be causal factors responsible for the
      process).

PMID- 14637256
TI  - Chemical rearrangement and repair pathways of 1,N6-ethenoadenine.
AB  - 1,N(6)-Ethenoadenine (epsilonA) is an exocyclic DNA adduct introduced to DNA by
      vinyl chloride and related compounds as well as in the consequence of oxidative
      stress and lipid peroxidation (LPO). This highly genotoxic DNA damage is
      chemically unstable and either depurinates or converts into pyrimidine ring
      opened secondary lesions. We have studied the structures of derivatives formed
      during epsilonA chemical rearrangement and identified enzymes repairing one of
      the rearrangement products. Rearrangement involves a water molecule addition to
      the C(2)-N(3) bond of epsilonA, resulting in formation of pyrimidine ring-closed
      B1 product, which is in equilibrium with pyrimidine ring-opened B2 compound. B2
      further deformylates to yield compound C. N-Glycosidic bond of compound C is
      unstable and C depurinates, yielding compound D. These secondary lesions are not
      repaired by alkylpurine DNA N-glycosylase, which excises the parental epsilon A.
      Compound B, when paired with thymine and cytosine is efficiently excised by
      Escherichia coli formamidopirymidine DNA N-glycosylase (Fpg), and thymine glycol
      DNA N-glycosylases from E. coli (Nth) and Saccharomyces cerevisiae (Ntg2). B is
      eliminated from B:G pair only by Nth and Ntg2 glycosylases, however none of the
      enzymes studied is excising B from B:A pair. This enables finishing of
      rearrangement, formation of AP sites and subsequently DNA strand breaks. During
      in vitro translesion synthesis, C is much easier bypassed by DNA polymerases,
      than compound B, and also than the parental epsilonA as well as than the AP site.
      This bypass beyond C proceeds mainly by misinsertion of adenine and guanine, or
      by insertion of thymine, the latter restoring the parental A:T pair.
      Alternatively, looping out of adducted nucleotide alone or with adjacent one
      generates one- or two-nucleotide deletions. This may explain the previously
      reported 20-fold higher mutagenic potency of product C in comparison to epsilon A
      in E. coli [Biochemistry 32 (1993) 12793].

PMID- 14637257
TI  - Enzymology of repair of etheno-adducts.
AB  - Etheno(epsilon)-adducts such as 1,N(6)-ethenoadenine (epsilon A), 3,N(4)
      ethenocytosine (epsilon C), N(2),3-ethenoguanine (N(2),3-epsilon G), and 1,N(2)
      ethenoguanine (1,N(2)-epsilon G) are produced in cellular DNA by two independent
      pathways: (i) by reaction with oxidised metabolites of vinyl chloride, 2
      chloroacetaldehyde and 2-chloroethylene oxide; (ii) by endogenous processes
      through the interaction of lipid peroxidation (LPO)-derived aldehydes and
      hydroxyalkenals. They have been found in DNA isolated from human and rodent
      tissues. However, the levels of adducts were significantly increased by cancer
      risk factors contributing to lipid peroxidation and oxidative stress. The highly
      mutagenic and genotoxic properties of epsilon-adducts have been established in
      vitro by analysing steady-state kinetics of primer extension assays and in vivo
      by site-specific mutagenesis in mammalian cells. Therefore, the repair processes
      eliminating exocyclic adducts from DNA should play a crucial role in maintaining
      the stability of genetic information. The epsilon-adducts are eliminated by the
      base excision repair (BER) pathway, with DNA glycosylases being the key enzymes
      of this pathway. They remove epsilon-adducts from DNA by hydrolysing the N
      glycosidic bond between the damaged base and deoxyribose, leaving an abasic site
      in DNA. The ethenobase-DNA glycosylases have been identified and their enzymatic
      properties described. They are specific for a given epsilon-base although they
      can also excise different types of modified bases, such as alkylated purines,
      hypoxanthine and uracil. The fact that ethenoadducts are recognised and excised
      with high efficiency by various DNA glycosylases in vitro suggests that these
      enzymes may be responsible for repair of these mutagenic lesions in vivo, and
      thus constitute important contributors to genetic stability.

PMID- 14637258
TI  - The interacting pathways for prevention and repair of oxidative DNA damage.
AB  - Genomes are damaged by spontaneous decay, chemicals, radiation and replication
      errors. DNA damage may cause mutations resulting in inheritable disease, cancer
      and ageing. Oxidative stress from ionising radiation and oxidative metabolism
      causes base damage, as well as strand breaks in DNA. Base damage is mostly
      indirect and caused by reactive oxygen species (ROS) generated, e.g. O2(.-)
      (superoxide radical), OH. (hydroxyl radical) and H2O2 (hydrogen peroxide). ROS
      also oxidise RNA, lipids, proteins and nucleotides. The first line of defence
      against ROS is enzymatic inactivation of superoxide by superoxide dismutase and
      inactivation of the less toxic hydrogen peroxide by catalase. As a second line of
      defence, incorporation of damaged bases into DNA is prevented by enzymes that
      hydrolyse oxidised dNTPs (e.g. 8-oxodGTP) to the corresponding dNMP. The third
      line of defence is repair of oxidative damage in DNA by an intricate network of
      DNA repair mechanisms. Base excision repair (BER), transcription-coupled repair
      (TCR), global genome repair (GGR), mismatch repair (MMR), translesion synthesis
      (TLS), homologous recombination (HR) and non-homologous end-joining (NHEJ) all
      contribute to repair of oxidative DNA damage. These mechanisms are also
      integrated with other cellular processes such as cell cycle regulation,
      transcription and replication and even use some common proteins. BER is the major
      pathway for repair of oxidative base damage, with TCR and MMR being important
      backup pathways for repair of transcribed strands and newly replicated strands,
      respectively. In recent years, several new DNA glycosylases that initiate BER of
      oxidative damage have been identified. These have specificities overlapping with
      previously known DNA glycosylases and serve as backups, and may have distinct
      roles as well. Thus, there is both inter- and intra-pathway complementation in
      repair of oxidative base damage, explaining the limited effects of absence of
      single DNA glycosylases in animal model systems.

PMID- 14637259
TI  - Antioxidant role of mulberry (Morus indica L. cv. Anantha) leaves in
      streptozotocin-diabetic rats.
AB  - BACKGROUND: The antihyperglycemic and antioxidant role of mulberry (Morus indica
      L.) leaves were investigated. METHODS: Streptozotocin (STZ)-induced diabetic male
      Wistar rats were used as experimental models; one group was given 25% dry
      mulberry leaf powder mixed with the standard diet and another group was given
      standard diet for a period of 8 weeks. The antihyperglycemic and antioxidant role
      of mulberry was assessed by determining its effect on blood glucose, lipid
      peroxidation, reduced glutathione (GSH) concentrations and on the activity of
      glucose-6-phosphate dehydrogenase (G6PDH) and various antioxidant enzymes in
      erythrocytes and compared with that of controls. RESULTS: Mulberry-treated
      diabetic rats showed a significant decrease in fasting blood glucose
      concentrations indicating a good glycemic control. Increased lipid peroxidation
      and the activity of catalase (CAT) in erythrocytes observed in diabetic controls
      were significantly decreased by mulberry leaves (48% and 33%, respectively).
      Decreased GSH concentrations and the activity of glucose-6-phosphate
      dehydrogenase and antioxidant enzymes viz., glutathione peroxidase (GPx),
      glutathione reductase (GR), glutathione-S-transferase (GST) and superoxide
      dismutase (SOD) observed in uncontrolled diabetes were improved (52%, 69%, 151%,
      95%, 24% and 106%) by mulberry treatment very efficiently. CONCLUSION: Mulberry
      leaves possess antihyperglycemic and antioxidant properties.

PMID- 14637260
TI  - Protective role of Egyptian propolis against tumor in mice.
AB  - BACKGROUND: Propolis has numerous biologic activities including antibiotic,
      antifungal, antiviral and anti-inflammatory properties. The present work is aimed
      to study the effect of crude Egyptian propolis on tumor in mice induced by
      Ehrlich ascitis carcinoma (EAC) cell line. RESULTS: The administration of
      propolis (160 mg/kg body weight), by gastric intubation 2 h before the
      intraperitoneal injection of EAC, effectively inhibited tumor growth and the
      proliferation of EAC. The tumor volume was markedly reduced from 7+/-0.9 ml in
      EAC-infected mice to 1.6+/-0.95 ml in propolis-treated mice. Also, the lipid
      peroxide level which was 13.3+/-1.24 nmol malodialdehyde (MDA)/mg protein in EAC
      infected mice was significantly decreased to 3.3+/-2.1 nmol MDA/mg protein.
      Reduced glutathione (GSH) and glutathione S-transferase (GST) concentrations were
      markedly increased in propolis-treated mice. This effect was associated with
      inhibition of cell cycle progression and induction of apoptosis. Administration
      of propolis 2 h before injection of EAC arrested cells in G0/G1 phase and
      resulted in a decrease in the viability, DNA, total RNA and protein level of
      tumor cells. CONCLUSIONS: Crude Egyptian propolis has a strong inhibitory
      activity against tumors. The anti-tumor mechanism may be mediated by preventing
      oxidative damage and induction of apoptosis.

PMID- 14637261
TI  - Atorvastatin reduces plasma MCP-1 in patients with acute coronary syndrome.
AB  - BACKGROUND: The monocyte chemoattractant protein-1 (MCP-1) is a chemokine
      responsible for the recruitment of monocytes to sites of inflammation. MCP-1 may
      play critical roles in plaque instability. Anti-inflammation may be one benefit
      of statin drugs in acute coronary syndrome (ACS). We investigated the effects of
      atorvastatin therapy on plasma MCP-1 concentrations and production of MCP-1
      released by peripheral blood monocytes from ACS patients. METHODS: Forty patients
      with ACS were randomly separated into two groups, those receiving conventional
      therapy (Group A, n=20), and conventional therapy+atorvastatin (10 mg/day, Group
      B, n=20). The study the effects of atorvastatin on secretion and expression of
      MCP-1, human peripheral blood monocytes from healthy donors were incubated with
      atorvastatin (0.1-10 micromol/l) for up to 24 h in vitro. MCP-1 concentrations in
      plasma and monocytes culture supernatants were measured by enzyme-linked
      immunosorbent assays (ELISA). MCP-1 expression was measured by RT-PCR. RESULTS:
      Plasma concentrations of MCP-1 were significantly lower after 4 weeks therapy in
      both groups of patients [Group A from 97.4 (50.1-164) to 72.6 (36.3-156) pg/ml,
      Group B from 101 (60-178) to 45 (29-91) pg/ml, (P<0.05, respectively)]. Compared
      with conventional therapy alone, atorvastatin significantly further reduced
      plasma MCP-1 concentrations. There was no significant correlation between the
      degree of changes in plasma MCP-1 and LDL-C. In vitro, atorvastatin inhibits
      production of MCP-1 up to 73%, in a concentration-dependent manner, and
      suppressed MCP-1 expression in peripheral blood monocytes. CONCLUSIONS:
      Atorvastatin reduced plasma MCP-1 concentrations in patients with ACS. These
      effects may explain some clinical benefits of statins in the treatment of these
      patients.

PMID- 14637262
TI  - Simultaneous gas-chromatographic measurement of rhamnose, lactulose and sucrose
      and their application in the testing gastrointestinal permeability.
AB  - BACKGROUND: As it is important to test gastric and intestinal permeability
      simultaneously in gastrointestinal disorders such as Celiac disease, we developed
      a gas-chromatographic (GC) method to estimate rhamnose (L-rh), lactulose (Lacl)
      and sucrose (Suc) in urine. METHODS: The method is based on the use of alditol
      acetate derivatives giving a lower number of GC peaks than reducing sugars do.
      Acetate derivatives are more stable and less expensive than GC silylates and keep
      the flame-detector cleaner. We checked the chemical stability of alditol acetates
      by verifying the reproducibility of the standard curve of a sugar derivative
      sample which had been stored for 2 months at -20 degrees C. RESULTS: The
      calibration proved linear over the range 0.1-1 microg of sugar injected.
      Analytical sugar recovery was 88%+/-19.4% (mean+/-S.D.) for rhamnose, 105%+/-7.4%
      for sucrose and 102%+/-2.4% for lactulose. Mean within-day precision (CV) was
      7.7% for rhamnose, 5.7% for sucrose and 1.9% for lactulose, and between-day (CV)
      was 6.7% for rhamnose, 3.9% for sucrose and 1.6% for lactulose. The rhamnose,
      lactulose and sucrose as the lactulose/rhamnose ratio clearly differentiated 25
      healthy controls from 36 patients with active gluten-sensitive enteropathy.
      CONCLUSIONS: A fast, reliable and cheap gas-chromatographic method is presented
      here to evaluate gastric and intestinal permeability.

PMID- 14637263
TI  - Do tissue damage biomarkers used to assess machine-perfused NHBD kidneys predict
      long-term renal function post-transplant?
AB  - BACKGROUND: Renal transplantation in many units is limited by the availability of
      donor organs. Kidneys obtained from non-heart-beating donors (NHBD) represent an
      important resource, with the potential to substantially increase the available
      donor organ pool. Such kidneys are associated with increased warm ischaemic
      tissue injury which may be assessed by hypothermic machine perfusion. Within our
      transplant centre, a key component of such damage assessment and viability
      screening involves the quantification of the tissue damage biomarkers glutathione
      S-transferase in kidney perfusates. METHODS: Since 1998, 126 NHBD kidneys were
      machine-perfused prior to implantation, resulting in 74 transplants. Kidney
      perfusate samples were assayed for glutathione S-transferase in "real time", and
      alanine aminopeptidase and fatty acid binding protein in "retrospect". RESULTS:
      The pre-transplant concentration of these tissue injury biomarkers determined pre
      transplant did not correlate with subsequent longer-term renal function, as
      assessed by measurement of serum creatinine (tGST: Spearman correlation r=-0.02;
      Ala-AP: r=0.02; H-FABP: r=-0.05) and creatinine clearance (tGST: r=0.08; Ala-AP:
      r=-0.02; H-FABP: r=0.14) for those kidneys that had passed their viability tests.
      CONCLUSIONS: Thus whilst these biomarkers may represent reliable pre-transplant
      indicators of immediate kidney viability and short-term kidney function, they do
      not predict the efficacy of renal function in the longer term.

PMID- 14637264
TI  - A new modified gamma-%CDT method improves the detection of problem drinking:
      studies in alcoholics with or without liver disease.
AB  - BACKGROUND: The detection of excessive alcohol consumption by laboratory methods
      continues to lack sensitivity and specificity. Recent studies have suggested that
      diagnostic improvement may be achieved by combining carbohydrate-deficient
      transferrin (CDT) and gamma-glutamyltransferase (GT) measurements into a marker
      defined as gamma-CDT. METHODS: We developed a new approach for determining gamma
      CDT by using the data obtained from the Axis %CDT turbidimetric assays. Marker
      results were compared in the assessment of 65 alcoholics, who were either with
      (n=34) or without (n=31) liver disease, as analysed by clinical, laboratory, and
      morphological criteria. Reference individuals were 45 healthy volunteers who were
      either social drinkers or abstainers. RESULTS: Gamma-GT and CDT results derived
      from both CDTect and %CDT measurements were used to calculate marker ratios as
      follows 0.8 x ln(GT)+1.3 x ln(CDT). With the established cut-off of 4.0 for the
      gamma-%CDT, the sensitivity of this method was 94% for men and 82% for women, as
      compared to 61% and 46% for %CDT and 70% and 73% for GT. The gamma-%CDT method
      was less dependent on liver status than the various other markers and showed the
      highest correlation with self-reported alcohol consumption (r=0.7254).
      CONCLUSIONS: The data indicates that the new gamma-%CDT method yields improved
      diagnostic accuracy for the detection of excessive ethanol consumption.

PMID- 14637265
TI  - Myoglobin stratifies short-term risk in acute major pulmonary embolism.
AB  - BACKGROUND: Concentrations of cardiac troponins can be elevated in acute
      pulmonary embolism (APE) indicating myocardial injury. Although concentration of
      myoglobin (MYO) increases after myocardial damage, even before detectable rise of
      cardiac troponin levels occurs, MYO was not evaluated in APE. Therefore, we
      assessed prevalence and prognostic significance of myoglobin in major APE.
      METHODS: We studied 46 patients (30 women, aged 61.9+/-17.8 years) with major APE
      defined with right ventricular dilatation. On admission serum myoglobin, and
      cardiac troponin T (cTnT) were measured. Serum MYO concentrations >58 ng/ml for
      women, and >72 ng/ml for men were considered abnormal. CTnT>0.01 ng/ml was
      regarded to indicate myocardial injury. RESULTS: MYO levels exceeding sex
      specific norms were found in 21/46 (45.7%) of patients, while detectable cTnT was
      found in 24/46 (52.1%) of patients. Seven patients died during hospitalization.
      Elevated MYO significantly predicted in-hospital mortality (OR 25, 95% CI 1.3
      474.2), while increased cTnT concentration did not affect the survival. Among
      clinical and echocardiographic variables only older age indicated worse prognosis
      (OR 1.6, 95% CI 1.06-2.41). CONCLUSIONS: Myoglobin levels are elevated in serum
      on admission in almost half of patients with major APE. Elevated myoglobin level,
      marker of myocardial injury, is a powerful predictor of increased risk of fatal
      outcome in major pulmonary embolism.

PMID- 14637266
TI  - HPLC analysis of some sulphur compounds in saliva: comparison between healthy
      subjects and periodontopathic patients.
AB  - BACKGROUND: Saliva is an easily available biological material that is not
      commonly analysed in clinical chemistry, while it could give useful information
      especially in several oral diseases. METHODS: In this work, the sulphur
      containing compounds cysteine, cysteinylglycine and glutathione were analysed in
      saliva of control subjects and periodontopathic subjects by a HPLC method. The
      detection limit of the method is 0.5, 0.1 and 0.1 micromol/l for cysteine,
      cysteinylglycine and glutathione, respectively, and it is linear up to 10 mmol/l.
      RESULTS: the median values for the control group are 1.2 micromol/l for cysteine
      and glutathione and 0.4 micromol/l for cysteinylglycine while those of
      periodontopathic patients are significantly increased (4.4, 2.1 and 11.0
      micromol/l for cysteine, cysteinylglycine and glutathione, respectively).

PMID- 14637267
TI  - Erythropoietin treatment in the neuropsychiatric porphyrias.
AB  - BACKGROUND: In a previous report, 31 patients with neuropsychiatric porphyria
      were studied and nine of these patients were anaemic in association with
      inappropriately low serum erythropoietin levels. We were also able to demonstrate
      that treatment with erythropoietin in non-porphyric patients (mainly diabetic
      patients with autonomic neuropathy) significantly reduced urinary delta
      aminolaevulinic acid levels. METHODS: We treated six porphyric patients, five of
      whom were anaemic, with recombinant human erythropoietin (1000-2000 IU thrice
      weekly). They were all in clinical but not biochemical remission. Full blood
      count, including reticulocytes and platelets, urinary delta-aminolaevulinic acid,
      porphobilinogen and total porphyrins were measured monthly. Baseline serum
      ferritin, vitamin B(12), folate and C-reactive protein levels were all within the
      normal range and serum creatinine did not exceed 126 micromol/l. RESULTS: After 3
      months of treatment, the average baseline haemoglobin increased significantly
      (p=0.01). When treatment was stopped, the haemoglobin decreased and after 3
      months pre-treatment, haemoglobin levels were reached. Urinary delta
      aminolaevulinic acid, porphobilinogen and porphyrin levels all tended to decrease
      during treatment with erythropoietin, but the difference between baseline and 3
      months of erythropoietin was statistically significant only for porphobilinogen
      (p=0.03). The severity of porphyria attacks was reduced and the quality of life
      increased during treatment with erythropoietin. CONCLUSION: We conclude that in
      some porphyric patients treatment with erythropoietin reduces urinary delta
      aminolaevulinic acid, porphobilinogen and porphyrin levels with an increase in
      well-being and a reduction in the severity of porphyria attacks.

PMID- 14637269
TI  - Production of polyacrylamide gradient gel for lipoprotein electrophoretic
      separation.
AB  - BACKGROUND: Small LDL are associated with risk of coronary heart disease.
      Gradient gel electrophoresis for LDL separation is not a simple method and high
      quality non-denaturing gradient gels are lacking. METHODS: In this paper, we
      describe a method for the preparation of a polyacrylamide gel system that
      consists of an upper linear gradient gel (1.8-10%) and a lower homogeneous gel
      (16%) for the determination of LDL size. RESULTS: The linear gradient is highly
      reproducible. Intra-inter gel coefficients of variation for LDL particle size are
      lower than 0.6%. CONCLUSION: Effective LDL size measurement from pre-stained
      serum samples is possible in a stable gel.

PMID- 14637268
TI  - Comparison of spectrophotometric and enhanced chemiluminescent assays of serum
      antioxidant capacity.
AB  - BACKGROUND: Over recent years, interest in total antioxidant capacity measurement
      in biological fluids has increased. A number of assays are now available, and we
      wished to compare an enhanced chemiluminescence (ECL) method to a
      spectrophotometric method, the total antioxidant status (TAS) assay. METHODS:
      Serum urate concentration, ECL and TAS were measured in 34 healthy subjects.
      Additionally, 10 subjects participated in a two-way, randomised crossover study,
      and received urate 1000 mg or vitamin C 1000 mg intravenously over 1 h. Serum ECL
      and TAS were measured at 0, 15, 30, 45, 60, 90 and 120 min after commencing
      infusion. RESULTS: Baseline measurements were poorly correlated between ECL and
      TAS assays, and between serum urate concentration and each antioxidant assay.
      There was good correlation between the change in antioxidant capacity detected by
      both assays during urate infusion (R=0.79, p<0.001, n=60), but not vitamin C
      infusion. CONCLUSIONS: ECL and TAS measures of serum antioxidant capacity
      correlate poorly in a healthy population, although both are sensitive to
      increases in circulating urate concentrations. Therefore, ECL and TAS appear
      sensitive to different factors. The comparative strengths and weaknesses of
      various antioxidant assays should be reviewed.

PMID- 14637270
TI  - Oxidant, antioxidant status and metabolic data in patients with beta-thalassemia.
AB  - BACKGROUND: In beta-thalassemia major impaired biosynthesis of beta globin leads
      to accumulation of unpaired alpha globin chain. An iron overload, usually
      observed, generates oxygen-free radicals and peroxidative tissue injury. AIM: To
      investigate hematological parameters, oxidative stress and the antioxidant
      capacity in beta-thalassemia patients compared to control subjects in order to
      determine their impact in several organs functions. METHODS: This study was
      conducted on 56 beta-thalassemia major patients compared to 51 healthy subjects.
      We determined metabolic parameters (glycaemia, lipid parameters, electrolytes,
      iron indices, hepatic, renal and heart functions tests), plasmatic thiobarbituric
      acid reactive substances (TBARS), plasmatic peroxyl radical trapping potential
      (TRAP), plasmatic superoxide dismutase (SOD), erythrocyte gluthathione peroxidase
      (GPX), plasmatic vitamin E, vitamin A and trace elements. RESULTS: Except
      triglycerides, lipid fractions were significantly decreased in beta-thalassemia
      compared to controls. Serum ferritin, iron, TBARS concentrations, SOD and GPX
      activities were significantly increased. But TRAP, vitamin E and zinc
      concentrations were significantly decreased. CONCLUSION: Our findings confirm the
      peroxidative status generated by iron overload in beta-thalassemia major patients
      and highlight the rapid formation of marked amounts of TBARS and the increase of
      SOD and GPX activity. Our study suggested that in beta-thalassemia the first
      organ impaired is the liver.

PMID- 14637271
TI  - Serum cystatin C is sensitive to small changes in thyroid function.
AB  - BACKGROUND: Serum cystatin C (CysC) is a novel marker for kidney function. The
      impact of mild thyroid dysfunction on CysC has never been investigated. METHODS:
      CysC was determined at the time of diagnosis of subclinical hypo- and
      hyperthyroidism, and when TSH returned into the normal range in 40 consecutive
      patients with mild thyroid dysfunction. RESULTS: Twenty-six patients with
      subclinical hypothyroidism and 14 patients with subclinical hyperthyroidism were
      included. In patients with subclinical hypothyroidism median (range) TSH was 7.8
      (4.3-26.7) mU/l (reference 0.27-4.2) at diagnosis and decreased to 2.3 (0.36-4.0)
      mU/l following treatment with levothyroxine. Mean (+/-S.D.) CysC increased from
      0.88+/-0.23 mg/l (reference 0.63-1.33) in the hypothyroid state to 1.01+/-0.21
      mg/l when TSH normalized (p<0.001). In patients with subclinical hyperthyroidism,
      median TSH at diagnosis was 0.08 (0.001-0.26) mU/l and increased to 1.6 (0.28
      4.0) mU/l in the euthyroid state. CysC declined from 1.04+/-0.29 mg/l at
      diagnosis of subclinical hyperthyroidism to 0.91+/-0.25 mg/l when TSH normalized
      (p<0.05). CONCLUSIONS: Mild thyroid dysfunction significantly alters CysC levels.
      Therefore, thyroid function has to be considered when CysC is used as a marker of
      kidney function.

PMID- 14637273
TI  - The role of plasma thiol compounds and antioxidant vitamins in patients with
      cardiovascular diseases.
AB  - BACKGROUND: Increased levels of homocysteine (Hcy) and cysteine (Cys) are
      associated with risk of cardiovascular diseases (CVD). These thiol compounds can
      generate various free radicals and so cause endothelial dysfunction. Antioxidant
      vitamins are effective scavengers of reactive oxygen species (ROS) and prevent
      endothelial dysfunction. In this study, we investigated the plasma homocysteine,
      cysteine, vitamins E, C and A, and beta-carotene (BC) levels in cardiovascular
      patients to compare with controls. We also investigated whether there is a
      correlation between the plasma thiol compounds and antioxidant vitamins. METHODS:
      Blood samples were collected from 47 patients with cardiovascular disease (16
      women and 31 men) and 21 healthy subjects (8 women and 13 men) in the overnight
      fasting state. Serum thiol compound and antioxidant vitamin levels were measured
      by high-pressure liquid chromatography (HPLC) methods. RESULTS: The plasma
      homocysteine and cysteine levels were significantly higher in patients than those
      of controls. While vitamin C (VC), vitamin A (VA) and beta-carotene levels were
      significantly lower in patients than in controls, vitamin E (VE) levels did not
      change in both groups. There is a positive correlation between homocysteine and
      cysteine levels (r=0.622, p=0.000) in all study population. We found that the
      plasma level of homocysteine was significantly correlated in negative manner with
      vitamins E and A levels (r=-0.260, p=0.033 and r=-0.255, p=0.036, respectively)
      of all study population. Plasma cysteine levels were negatively correlated with
      only vitamin C levels (r=-0.320, p=0.008) in all study populations. CONCLUSIONS:
      Our data suggest that Hcy and Cys are associated with cardiovascular disease and
      there is negative but weak correlation's between thiol compounds and antioxidant
      vitamins.

PMID- 14637272
TI  - The effect of vitamin E supplementation on antioxidant enzyme activities and
      lipid peroxidation levels in hemodialysis patients.
AB  - BACKGROUND: This study has been undertaken to investigate the possible
      alterations of oxidant/antioxidant status in uremic patients undergoing
      hemodialysis (HD) and the effects of vitamin E supplementation. METHODS:
      Erythrocyte antioxidant enzyme activities [glutathione peroxidase (GSHPx),
      superoxide dismutase (SOD) and catalase (CAT)] and thiobarbituric acid reactive
      substance (TBARS) concentrations as a measure of lipid peroxidation in HD
      patients have been determined and compared with healthy controls. The patient
      group consisted of 36 uremic patients 21-75 years of age undergoing maintenance
      HD three times weekly for an average of 41 months. The efficiency of Vitamin E
      therapy in dialysis patients was also assessed by re-evaluating antioxidant
      status of the same patients after supplementation of the vitamin E in a dosage of
      600 mg/daily for 14 weeks. RESULTS: A significant decrease in the activities of
      erythrocyte SOD, CAT and GSHPx and a significant increase in TBARS concentrations
      were found in patient group compared to control group (p<0.001). A significant
      correlation between GSHPx activities and duration of HD therapy was also observed
      (r=-0.46, p<0.01). Vitamin E supplementation caused an increase in GSHPx and SOD
      activities and a decrease in TBARS concentrations. A slight but not significant
      increase in CAT activity was also observed by Vitamin E. CONCLUSIONS: The results
      suggest the presence of an oxidative activity and the possible preventive role of
      Vitamin E therapy in uremic patients undergoing HD.

PMID- 14637274
TI  - Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite
      Triage BNP assay.
AB  - BACKGROUND: Brain natriuretic peptides (BNPs) are useful in the assessment of
      heart failure, left ventricular dysfunction, and acute coronary syndromes.
      METHODS: We performed a multicenter evaluation of the automated Roche NT-proBNP
      assay and compared its performance to the Biosite Triage BNP assay. RESULTS: The
      N-terminal (1-76) pro brain natriuretic peptide (NT-proBNP) method is precise
      (CV<or=6.1%), has a wide dynamic measuring range (30-35000 ng/l), is free from
      common interferences, and does not cross-react with BNP. EDTA or heparinized
      plasma samples collected in glass or plastic tubes can be used, and samples are
      stable at room temperature or 4 degrees C for up to 3 days. In contrast, the
      Biosite BNP assay has >2-fold higher CV, and plasma samples are more labile when
      stored at room temperature and 4 degrees C. Comparison studies showed a
      reasonable correlation between NT-proBNP and BNP assays, with a substantially
      higher slope bias of 6-20 for the NT-proBNP assay. CONCLUSIONS: The automated
      Roche NT-proBNP assay has good analytical performance and better precision than
      the Biosite BNP assay. Unlike BNP, NT-proBNP is stable in EDTA plasma for 3 days
      at room temperature or longer at 4 degrees C. The Roche NT-proBNP is fully
      automated and will accommodate the testing of large numbers of clinical samples
      for assessing cardiac dysfunction.

PMID- 14637275
TI  - Gene polymorphisms in tumor necrosis factor locus and waist-hip ratio in obese
      Koreans.
AB  - BACKGROUND: The study was designed to investigate the association among tumor
      necrosis factor-beta (TNFbeta)+252A/G, TNF-alpha (TNFalpha)-308G/A polymorphisms
      and anthropometric parameters related to obesity in Korean obese subjects.
      METHODS: The study included 152 obese healthy subjects (BMI>or=25 kg/m(2), range
      25.0-40.4, age range 15-40 years) and 82 non-obese controls (BMI<25 kg/m(2), age
      range 15-40 years). Total fat mass and percent body fat were determined by dual
      energy X-ray absorptiometry (DEXA). Genomic DNA was extracted and used for NcoI
      restriction fragment length polymorphism (RFLP)-based genotyping of TNF. RESULTS:
      No differences were observed for allelic and genotype frequencies between obese
      and non-obese subjects. Also, no association of TNF polymorphisms was observed
      with body mass index (BMI) for genotype in obese subjects. In addition, age,
      percent body fat, BMI and cholesterol concentrations did not differ from TNF
      genotypes. However, waist-to-hip ratio (WHR) was significantly decreased in
      subjects with TNFalpha A/TNFbeta G haplotype compared with other haplotypes
      carriers (0.92+/-0.03 vs. 0.94+/-0.06, P=0.005). CONCLUSIONS: These results
      suggest that TNF polymorphisms at position -308 and +252 are not a significant
      factor for BMI, but affect the WHR in obese Koreans.

PMID- 14637276
TI  - Antioxidant status in rheumatoid arthritis and role of antioxidant therapy.
AB  - BACKGROUND: Oxygen free radicals have been implicated as mediators of tissue
      damage in patients of rheumatoid arthritis (RA). This study was designed to
      elucidate plasma oxidant/antioxidant status in rheumatoid arthritis, with the aim
      of evaluating the importance of antioxidant therapy in the management of this
      disease. METHODS: The study included 40 patients of rheumatoid arthritis who were
      randomly divided into two subgroups of 20 each. One group received conventional
      treatment for 12 weeks and in the other group conventional treatment was
      supplemented with antioxidants for the same duration. Twenty age- and sex-matched
      normal individuals constituted the control group. Blood samples of controls and
      patients were collected at the time of presentation and analyzed for total
      thiols, glutathione, vitamin C and malondialdehyde (MDA-marker of oxidative
      stress). The investigations were repeated in the patients after 12 weeks.
      RESULTS: The blood concentrations of total thiols, glutathione and vitamin C were
      found to be significantly lower in rheumatoid arthritis patients as compared to
      healthy controls, while the concentrations of MDA were much higher. There was a
      statistically significant increase in the posttreatment concentrations of these
      antioxidants, along with a decrease in the concentrations of MDA. CONCLUSIONS:
      The antioxidant defense system is compromised in rheumatoid arthritis patients.
      There is a shift in the oxidant/antioxidant balance in favor of lipid
      peroxidation, which could lead to the tissue damage observed in the disease. The
      results suggest the necessity for therapeutic co-administration of antioxidants
      along with conventional drugs to such patients. However, due to the limited
      number of cases included in this study, more studies may be required to
      substantiate the results and arrive at a definite conclusion, in terms of safety
      and efficacy of adding on antioxidant therapy for the treatment of RA.

PMID- 14637277
TI  - Effects of storage time on stability of salivary immunoglobulin A and lysozyme.
AB  - BACKGROUND: In many research settings, storage of samples prior to analysis is
      unavoidable. This study investigates the effects of storage time on stability of
      salivary immunoglobulin A (IgA) and lysozyme. METHODS: Saliva samples were
      obtained from 30 healthy adults. Each sample was divided into five aliquots and
      stored at -30 degrees C until analysis. The samples were measured for IgA and
      lysozyme concentrations after 1, 2, 3, 8 and 12 months of storage using enzyme
      linked immunosorbent assay. RESULTS: There was a decline in the concentrations of
      IgA and lysozyme with increasing storage time. Repeated measures analyses for
      both salivary IgA and lysozyme showed a significant difference after 8 months of
      storage as compared to the 1st month (p<0.05). IgA levels decreased significantly
      with % change in majority of the samples >10% after storage for 8 months or more.
      A similar pattern was observed for lysozyme with % change in majority of the
      samples >14% levels when the samples were assayed at 8th month and beyond (mean%
      change+/-S.D.>14%). CONCLUSION: Salivary IgA and lysozyme concentrations remain
      stable for up to 3 months when stored at -30 degrees C. These findings have
      important implications with regard to measurement validity of salivary biomarkers
      research.

PMID- 14637278
TI  - Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell
      activation.
AB  - BACKGROUND: Curcumin, a major yellow pigment and active component of turmeric
      powder extracted from Curcuma longa L. (Gingiberaceae), has been shown to possess
      anti-inflammatory and anti-cancer activities. Protease-activated receptors (PARs)
      play a role in inflammation, and human leukemic mast cells (HMC-1) co-express
      PAR2 and PAR4. In the present study, the effect of curcumin on PAR2- and PAR4
      mediated HMC-1 activation was examined. METHODS: HMC-1 cells were stimulated with
      trypsin (100 nmol/l, PAR2 and PAR4 agonist), SLIGKV-NH(2) (100 microM, PAR2
      activating peptide) or GYPGQV-NH(2) (100 micromol/l PAR4-activating peptide) in
      the presence or absence of curcumin (1, 10, and 100 micromol/l). TNF-alpha
      secretion was measured by enzyme-linked immunosorbent assay (ELISA). TNF-alpha
      and tryptase mRNA were measured by reverse-transcription PCR (RT-PCR). Mitogen
      activated protein kinase (MAPK) activation was assessed by Western blot analysis.
      Trypsin activity was measured using the substrate Bz-DL-Arg-p-nitroanilide
      (BAPNA). RESULTS: Curcumin (10 and 100 micromol/l) inhibited TNF-alpha secretion
      from trypsin or activating peptide-stimulated HMC-1. Curcumin (10 and 100
      micromol/l) also inhibited TNF-alpha and tryptase mRNA expression in trypsin
      stimulated HMC-1. Furthermore, curcumin inhibited trypsin-induced extracellular
      signal-regulated kinase (ERK) phosphorylation. However, curcumin did not affect
      the trypsin activity even at 100 micromol/l. CONCLUSION: Curcumin inhibits PAR2-
      and PAR4-mediated human mast cell activation, not by inhibition of trypsin
      activity but by block of ERK pathway.

PMID- 14637279
TI  - Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase
      activities, glutathione, nitric oxide, and malondialdehyde concentrations in
      serum of patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is a rare neoplasm that comprises
      a substantial proportion of all leukemias in middle-aged persons and is the most
      common type among elderly persons. The major causes are not known nor is there a
      detailed understanding about how the elusive origin(s) may relate to clinical
      expression, basic biological mechanisms, or pathogenesis. METHODS: Glutathione
      peroxidase (GSH-Px), glutathione reductase (GRD), Cu-Zn superoxide dismutase (Cu
      Zn SOD) activities, glutathione (GSH), nitric oxide (NO(*), and malondialdehyde
      (MDA) concentrations were measured in serum of patients with CLL and a healthy
      control group. RESULTS: Serum GSH-Px, Cu-Zn SOD activities, GSH concentration
      were lower in patients with CLL while serum NO(*) and MDA concentrations were
      higher in these patients compared with the control group. Serum GRD activity was
      not statistically significant in patients with CLL compared with the control.
      However, there was no statistically significant difference in the parameters on
      the basis of stages in these patients. Serum GSH concentration negatively
      correlated with serum MDA (r=30.63, p<0.05) and NO(*) concentrations (r=0.72,
      p<0.05) in patients with advanced stage (III+IV). However, no other correlation
      could be found among the parameters in healthy controls and patients with CLL
      CONCLUSIONS: There is significant changes in antioxidant defense system in CLL
      cases, which may lead to enhanced action of oxygen radical, resulting in lipid
      peroxidation.

PMID- 14637280
TI  - Remnant-like particles from subjects who died of coronary artery disease suppress
      NO synthase activity and attenuate endothelium-dependent vasorelaxation.
AB  - BACKGROUND: Plasma levels of remnant-like particles (RLP) is one of the
      predictive markers for coronary artery disease (CAD), and the inhibition by RLP
      of endothelium-dependent vasorelaxation has been reported. We attempted to
      clarify whether or not RLP, which inhibits endothelium-dependent vasorelaxation,
      affects nitric oxide (NO) production and NO synthase (eNOS) levels in cultured
      endothelial cells. METHODS: RLP were obtained from postmortem blood of subjects
      who died of CAD. Modification by RLP of acetylcholine-induced relaxation of
      rabbit aorta, and changes in NO production and (eNOS) in cultured bovine
      endothelial cells were examined. RESULTS: RLP at 750 and 1500 microg
      triglyceride/ml inhibited vasorelaxation, and at 5-160 microg triglyceride/ml,
      concentration-dependently inhibited NO production. However, (eNOS) did not
      decrease after incubation with RLP. CONCLUSION: Postmortem RLP from subjects who
      died of CAD do not change the amount of (eNOS), but rather, inhibits its activity
      and attenuates endothelium-dependent vasorelaxation.

PMID- 14637281
TI  - Moderate hyperhomocysteinaemia and immune activation in patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Moderate hyperhomocysteinaemia related to folate deficiency has been
      described in patients with cardiovascular risk and also in patients with
      autoimmune diseases including rheumatoid arthritis (RA). METHODS: In 33 patients
      with RA, serum concentrations of homocysteine and cysteine, of B-vitamins folate
      and vitamin B(12), and of immune activation markers neopterin and soluble 75-kDa
      TNF-receptor (sTNF-R75) were measured. RESULTS: A significant proportion of
      patients presented with elevated homocysteine and cysteine concentrations in
      comparison to reference ranges of healthy control persons. Moderate
      hyperhomocysteinaemia coincided with decreased serum folate and with higher
      concentrations of sTNF-R75 and neopterin, but it was rather independent from
      methotrexate (MTX) therapy. CONCLUSIONS: The coincidence of higher homocysteine
      and lower folate concentrations with increased concentrations of immune
      activation markers in patients with RA suggests that immune activation could be
      involved in the development of hyperhomocysteinaemia.

PMID- 14637282
TI  - Report of the II European symposium on clinical laboratory and in vitro
      diagnostics industry: "physiological reference values: a shared business?".

PMID- 14637283
TI  - Arginase in patients with breast cancer.

PMID- 14637284
TI  - Using a GIS-based floating catchment method to assess areas with shortage of
      physicians.
AB  - This paper presents a geographic information system (GIS) based floating
      catchment method for identifying physician shortage areas. The traditional
      designation methods are primarily regional availability measures, which use
      administrative boundaries such as counties as the basic spatial units for
      calculating physician to population ratios and designate shortage based on those
      ratios. Such approaches have been criticized for their inability to account for
      either the spatial variations of population demand and physician supply within
      those boundaries or for population-physician interactions across them. The
      floating catchment method addresses the internal spatial distribution problem by
      deriving population data from a smaller unit, the census tract. The potential
      cross border patient-physician interaction is taken into consideration by using
      circles of reasonable radius around each census tract centroid as the basic
      spatial units, which can encompass areas on either side of an administrative
      border. By varying the radius of the catchment circle, this paper demonstrates
      that the physician to population ratio is scale dependent and that the greatest
      variability of the ratios and shortages occur at the most local scales (< 20
      miles), which argues for using finer spatial resolution data in shortage
      designation practice.

PMID- 14637285
TI  - Modelling determinants of child mortality and poverty in the Comoros.
AB  - Based on the Demographic and Health Survey of the Comoros of 1996, the analysis
      of the determinants of child mortality reaches three conclusions. Firstly,
      differentiated analytical options generate partially convergent results and
      provide different dimensions of child mortality. Secondly, the study shows that
      the low standard of living of households in terms of assets is associated with
      high child mortality. Thirdly, the determinants of infant and infanto-juvenile
      mortality are relatively comparable. On the one hand, some common factors to both
      analytical options affect negatively child health: (i) geographical location in
      rural zones and/or on the islands of Anjouan and Moheli; (ii) the low standard of
      living of households in terms of assets; (iii) some community elements, in
      particular morbidity, the insufficiency of vaccination and the absence of
      childbirth assisted by qualified persons. On the other hand, characteristics of
      mothers and births have an impact on infant and infanto-juvenile survival.

PMID- 14637286
TI  - Women's management of the household health environment: responding to childhood
      diarrhea in the Northern Areas, Pakistan.
AB  - This paper examines mothers' management of water, sanitation, hygiene, and
      childhood diarrhea in a mountain community in the Northern Areas, Pakistan. It
      draws upon qualitative data obtained from 65 in-depth interviews and other
      ethnographic field methods. The analysis shows that respondents were familiar
      with diarrhea control interventions carried out in the study site, and associated
      childhood diarrhea with oral-fecal transmission routes such as poor water
      quality, unhygienic behaviors, contaminated food, and inadequate sanitation
      practices. Findings also demonstrate the continuance of long-established cultural
      patterns of perception and behavior with regard to childhood diarrhea and the
      influence of socio-economic constraints to instituting new management practices.

PMID- 14637287
TI  - (Re)placing health and health care: mapping the competing discourses and
      practices of 'traditional' and 'modern' Thai medicine.
AB  - In the wake of the AIDS crisis, 'traditional' Thai medicine has received new
      attention as a means by which people living with HIV and AIDS (PLWHA) can receive
      some level of care. The revitalization of Thai medicine, however, is complicated
      by the competing organizational politics and social dynamics that regulate
      discourses and practices of health and health care in Thailand. This paper
      examines how Thai medicine is being (re)placed in the context of competing health
      care systems and practices. Specifically, this analysis focuses on the complex
      interrelationships between 'traditional,' holistic medicine and 'modern,'
      allopathic medicine in a Thai context; and investigates the role of 'Thai
      medicine' (phaet phaen thai) and 'village medicine' (phaet pheun baan) as part of
      governmental and non-governmental efforts to provide health care to PLWHA in
      Chiang Mai, Thailand. The provision of such health care, however, takes place
      within the context of a struggle over 'local knowledge' and 'global change' and
      the ways in which places are organized in relation to the available treatment
      regimens for HIV/AIDS care. What this paper suggests is that the meanings of
      health and health care are inextricably linked to the complex, contested nature
      of social relations as they flow in, and are reworked through, particular places.

PMID- 14637288
TI  - Health inequalities in rural China: evidence from HeBei Province.
AB  - The purpose of this study was to examine the degree to which commonly used social
      class indicators-education, income, and occupation-are associated with health in
      the context of rural China. Data were collected from 10,226 individuals of
      working age (16-60) living in HeBei Province, the PRC. The association between
      education and income observed resembles the patterns documented in industrial
      societies, but the health status of farmers is quite similar to that of white
      collar employees. Persons in other than mainstream occupations report the poorest
      health status. Social selection and the costs of relative deprivation appear to
      be useful to the understanding of health inequality in rural China, though in a
      manner shaped by the particular social context.

PMID- 14637289
TI  - Water needs and women's health in the Kumasi metropolitan area, Ghana.
AB  - This paper examines the impact of water fetching by women and the quality of
      water during periods of water scarcity on the health of women in the Kumasi
      metropolitan area. A sample of 210 women drawn using systematic random procedure
      is used for the study. Formal interview is the main instrument used. The survey
      has established that income, quality of water, hours spent fetching water during
      scarcity and age are the main factors influencing women's health in the
      metropolis during water scarcity. In both the core and periphery, the water
      related problem influencing health is hours spent fetching water during scarcity.
      An empirical model on water needs and women's health has emerged from the survey.
      Recommendations have been made on strategies to ensure regular volume of surface
      water, effective management of scarce water resources with the participation of
      women, and ensuring gender equity in domestic services.

PMID- 14637290
TI  - Fat, rich and beautiful: changing socio-cultural paradigms associated with
      obesity risk, nutritional status and refugee children from sub-Saharan Africa.
AB  - There has been an increase in Australia's intake of refugees and migrants from
      sub-Saharan Africa over the last two decades. These refugees have been exposed to
      nutritional risks prior to migration, which, together with changes associated
      with acculturation, impact on their health and nutritional status post-migration.
      However, there is a paucity of data in Australia that has examined the health and
      nutritional status of this ethnic minority in Australia. Despite basic research
      assessing the nutritional status of children, none have specifically concentrated
      on the health and nutritional situation of sub-Saharan refugee children. In the
      absence of such studies, this paper explores issues relating to obesity in sub
      Saharan African refugee children within a cultural and public health framework.
      We begin by outlining the history of obesity and its cultural meaning. We then
      move to a consideration of predisposing factors for obesity and how these factors
      translate into obesity risk contexts of sub-Saharan refugees post-migration. We
      argue there are a number of key challenges related to culture and the
      relationship between socio-economic factors post-migration that require
      addressing by health professionals, dieticians and health educators to ensure the
      delivery of successful health outcomes.

PMID- 14637293
TI  - Development and implementation of a multi-centre information system for
      paediatric and infant critical care.
AB  - BACKGROUND: With no UK collective information system, a need existed to establish
      an integrated information system for public and private sector hospitals
      providing paediatric and infant critical care services. A lack of information in
      the past made it difficult for those procuring, providing and monitoring services
      to make informed, evidence-based decisions using reliable integrated data.
      OBJECTIVES: To develop and implement a collective multi-purpose information
      system for paediatric and infant critical care that was easily adaptable to any
      UK infant or paediatric critical care setting. Information outputs had to fulfil
      policy requirements and meet the needs of stakeholders. METHOD: Two minimum
      datasets, corresponding data definitions, survey forms and a user database were
      developed through a process of consultation by utilising an information
      partnership. Design, content, development and implementation issues were
      identified, discussed and resolved through a co-ordinated collaborative process.
      RESULTS: Data collection was implemented in all London and Brighton National
      Health Service (NHS) general and cardio-thoracic paediatric intensive care (PIC)
      units, several private PIC units and one NHS tertiary referral neonatal unit
      (NNU) 24 months from project start. CONCLUSIONS: The development of universal
      integrated information systems for defined settings of care is achievable within
      reasonable timeframes; however, successful development and implementation
      requires working within an information partnership to maximise co-ordination, co
      operation and collaboration. Those collecting and using data must be identified
      and involved in all aspects of development from project start. Financial and
      manpower resources must be well planned. Datasets should be as small as possible
      in order to make the collection of complete and valid data realistically
      achievable. When considering service-based information needs, considerable
      thought should be given to a multi-purpose; multi-use approach based on the most
      refined minimum dataset possible.

PMID- 14637294
TI  - Patients' sleep in an intensive care unit--patients' and nurses' perception.
AB  - The main purpose of this study was to describe how patients treated in an
      intensive care unit (ICU) perceive their sleep and to compare patients' and
      nurses' perceptions of the patients' sleep. The study also determined the
      percentage of patients in the ICU who were able to fill in the Richard Campell
      Sleep Questionnaire (RCSQ). This instrument consists of six items and utilises a
      visual analogue scale (VAS). The results of five of the RCSQ questions are used
      to calculate a total sleep score, ranging between 0 and 100 (0=the worst possible
      sleep, 100=the best sleep).Approximately half of the patients were able to answer
      the RCSQ (n=31). The patients' rating of their sleep varied widely (total sleep
      score: range 0-97, mean 45.5). Patients who had received hypnotics or sedatives
      during the night (n=12) had a significantly lower total sleep score (mean=31.6)
      than the rest of the patients (mean 54.3; P=0.037). On comparing the patients'
      and the nurses' perceptions of the patients' sleep, no significant difference
      between the groups was seen. This indicates that nurses can use the RCSQ to
      assess the sleep of patients who are unable to report their sleep themselves.

PMID- 14637295
TI  - Intensive care sedation of mechanically ventilated patients: a national Swedish
      survey.
AB  - Sedation in critically ill patients is a complex issue and at the same time an
      important concept for ensuring patient comfort. The aim of this study was to
      review the current practice of sedation for patients on mechanical ventilation in
      Swedish intensive care units (ICUs). Questionnaires were sent by post to head
      nurses in 89 ICUs with mechanically ventilated patients. By August 2000, 87 (98%)
      questionnaires had been returned. The results show that mechanically ventilated
      patients were routinely sedated in 91% of ICUs. Midazolam or propofol in
      combination with an opioid were the drugs preferred by 76%. Heavy sedation was
      most usual in 63% of ICUs but, when asked about the sedation level preferred by
      nurses, 78% chose light sedation (P=0.001). Only 16% used sedation scales. This
      study indicates that local habits and personal attitudes seem to have a great
      impact on sedation routines. It therefore appears worthwhile for ICUs to review
      their practice and, if necessary, to consider implementing sedation scales and
      sedation guidelines. Research pertaining to potential complications and patient
      comfort in relation to different sedation levels as well as further validation of
      the efficacy of sedation scales is needed.

PMID- 14637296
TI  - Researching the experience of being critically ill: some methodological
      difficulties.
AB  - The experience of being critically ill and being a patient in a critical care
      unit has attracted considerable research interest in recent years. Evidence of
      this is apparent in the increasing development of critical care follow-up
      services in many of our hospitals in the United Kingdom. However, actually
      conducting research this area can be fraught with difficulties and problems.
      Research participants may be extremely vulnerable during their recovery, making
      the methodological considerations crucial, in any study, which aims to explore
      the experiences of survivors. This paper explores some of the difficulties the
      researcher can face when researching this area.

PMID- 14637297
TI  - Levosimendan.

PMID- 14637298
TI  - The legacy of the clergy abuse scandal.

PMID- 14637299
TI  - Behavioral problems among children whose mothers are abused by an intimate
      partner.
AB  - OBJECTIVES: To determine the association between children's exposure to maternal
      intimate partner violence (IPV) and behavior problems as measured by the parent
      report version of the Child Behavior Checklist (CBCL). METHODS: The study
      population was comprised of 167 2- to 17-year-old children of Seattle women with
      police-reported or court-reported intimate partner abuse. The CBCL normative
      population served as the comparison group. Risk of behavior problems was
      calculated among the exposed children, in the presence and absence of a history
      of reported child maltreatment, relative to the normative population. Multiple
      logistic regression served as the primary method of analysis. RESULTS: Children
      exposed to maternal IPV were more likely to have borderline to clinical level
      scores on externalizing (i.e., aggressive, delinquent) behavior (RR=1.6, 95% CI:
      1.2, 2.1) and total behavioral problems (RR=1.4, 95% CI: 1.1, 1.9) compared to
      the CBCL normative sample after adjusting for age and sex. Children who were
      exposed to maternal IPV and were victims of child maltreatment were more likely
      to receive borderline to clinical level scores on internalizing (i.e., anxious,
      depressed) behaviors (RR=2.6, 95% CI: 1.5, 3.6), externalizing (i.e., aggressive,
      delinquent) behaviors (RR=3.0, 95% CI: 1.9, 4.0) and total behavioral problems
      (RR=2.1, 95% CI: 1.2, 3.2) compared to the CBCL normative sample after adjusting
      for age and sex. CONCLUSIONS: Exposure to maternal IPV is significantly
      associated with child behavioral problems both in the presence and absence of co
      occurring child maltreatment. Appropriate attention to the mental health of
      children living in households with IPV is needed.

PMID- 14637300
TI  - Childhood emotional abuse and neglect as predictors of psychological and physical
      symptoms in women presenting to a primary care practice.
AB  - OBJECTIVE: There were two aims to this study: first to examine whether emotional
      abuse and neglect are significant predictors of psychological and somatic
      symptoms, and lifetime trauma exposure in women presenting to a primary care
      practice, and second to examine the strength of these relationships after
      controlling for the effects of other types of childhood abuse and trauma. METHOD:
      Two-hundred and five women completed the Childhood Trauma Questionnaire
      (Bernstein et al., 1994), Trauma History Questionnaire (Green, 1996), the Symptom
      Checklist-revised (Derogatis, 1997), and the Revised Civilian Mississippi Scale
      for posttraumatic stress disorder (Norris & Perilla, 1996) when presenting to
      their primary care physician for a visit. Hierarchical multiple regression
      analyses were conducted to examine unique contributions of emotional abuse and
      neglect variables on symptom measures while controlling for childhood sexual and
      physical abuse and lifetime trauma exposure. RESULTS: A history of emotional
      abuse and neglect was associated with increased anxiety, depression,
      posttraumatic stress and physical symptoms, as well as lifetime trauma exposure.
      Physical and sexual abuse and lifetime trauma were also significant predictors of
      physical and psychological symptoms. Hierarchical multiple regressions
      demonstrated that emotional abuse and neglect predicted symptomatology in these
      women even when controlling for other types of abuse and lifetime trauma
      exposure. CONCLUSIONS: Long-standing behavioral consequences may arise as a
      result of childhood emotional abuse and neglect, specifically, poorer emotional
      and physical functioning, and vulnerability to further trauma exposure.

PMID- 14637301
TI  - Child sexual and physical abuse among college students in Singapore and the
      United States.
AB  - OBJECTIVES: The purpose of this study was to explore differences in rates and
      characteristics of child sexual and physical abuse experiences among women in
      Singapore and the US. METHOD: Participants (N=153) completed an anonymous
      questionnaire which assessed experiences of childhood sexual and physical abuse,
      abuse characteristics (e.g., victimization age, severity), and behavioral and
      subjective reactions to such experiences (e.g., labeling of experiences as abuse,
      psychological symptomatology). Exposure to other forms of traumatic life events
      was also assessed. RESULTS: In comparison to Singaporean women, US women were
      more likely to report a history of child sexual abuse, and to report experiencing
      more severe forms of sexual abuse. Women in Singapore were more likely than women
      in the US to report a history of child physical abuse, to report experiencing
      injury as a result of the abuse, and to disclose the abuse. Singaporean women
      with a history of child sexual abuse reported elevated psychological symptom
      levels relative to their nonabused peers and to US women with a history of child
      sexual abuse, even after controlling for exposure to other types of traumatic
      events. No significant differences in symptomatology with regard to child
      physical abuse were observed. CONCLUSIONS: Although preliminary in nature, the
      present findings are among the first to demonstrate differences in psychological
      adjustment between sexually abused and nonabused Asian women living in Asia. This
      study also provides some of the first support for cross-national differences in
      the psychological adjustment of child sexual abuse survivors.

PMID- 14637302
TI  - The complexity of trauma response: a 4-year follow-up of adolescent Cambodian
      refugees.
AB  - OBJECTIVE: The objective of this study was to document the psychosocial
      adjustment of young refugees during their adolescence and its association with
      the war-related trauma experienced by their family before migration. METHOD: Data
      were collected on 57 young Khmer resettled in Montreal and followed from early to
      late adolescence. The associations between premigratory exposure to political
      violence and postmigratory mental health and social adjustment were estimated for
      early, mid-, and late adolescence. RESULTS: The associations between premigratory
      exposure to political violence and postmigratory psychosocial adjustment
      fluctuated over the adolescence period. Overall, the adolescents whose families
      were more highly exposed to political violence tended to report a more positive
      social adjustment and less mental health symptoms than those less exposed.
      CONCLUSION: The high expectations of Cambodian parents towards their children and
      the preservation of traditional values despite the Khmer rouge attempts to
      eradicate them might contribute to explain the paradoxical association between
      the families' exposure to political violence and the adolescents' psychosocial
      adjustment in the host country. Although children and adult refugees seen in
      clinical setting are reminders of the negative effects of adversity, resilience
      should be more systematically explored in community samples to further our
      understanding of the long-term effects of trauma.

PMID- 14637303
TI  - [Contextual factors associated with the symptoms of teenagers victims of
      intrafamilial sexual aggression].
AB  - OBJECTIVE: The aim of the study was to identify the unique contribution of three
      sets of contextual factors (maternal supports, family problems and
      characteristics of the sexual aggression) on adolescents' post-disclosure
      symptoms. All participants were abused by a family member. METHOD: A total of 71
      adolescents girls were recruited from youth center services across Quebec.
      Psychological distress was evaluated with "Trauma Symptoms Checklist for
      Children" (TSC-C; Briere, 1989). Adolescents also completed self-report
      instruments and semi-structured interviews to evaluate contextual factors.
      RESULTS: Regression analyses indicated that general maternal support explain more
      variance in most of TSC-C symptoms than maternal response to disclosure. Analysis
      highlight that alcohol problems in family and various characteristics of sexual
      aggression explain a unique part of variance of several symptoms. CONCLUSIONS:
      The discussion addresses the need to continue to explore these questions with
      more specific instruments to evaluate family problems. A large spectrum of
      symptoms should also be considered.

PMID- 14637304
TI  - Big girls don't cry: the effect of child witness demeanor on juror decisions in a
      child sexual abuse trial.
AB  - OBJECTIVE: This study investigated the effect of child witness demeanor (defined
      as crying) on mock jurors' decisions in a simulated First-Degree rape trial.
      METHOD: One hundred and thirty-three undergraduates serving in the role of mock
      jurors read a trial summary in which the primary independent variable was the
      demeanor of the alleged child victim (i.e., calm, teary, hysterical crying). In
      addition to reading the summary, participants viewed pencil drawings of the
      witnesses that were presented as "courtroom drawings." RESULTS: The results
      showed that the teary condition led to more guilty verdicts and a greater belief
      in the alleged victim than the other demeanor conditions. CONCLUSIONS: Findings
      from this study indicate that demeanor can impact the perception of a child who
      is an alleged sexual assault victim in court. However, it is not simply the case
      that any display of demeanor will lead to a positive outcome for the alleged
      victim. Instead, it appears that too little or too much emotion from the alleged
      child victim negatively affected credibility in the eyes of the mock jurors.

PMID- 14637305
TI  - Depressed skull fractures: a pattern of abusive head injury in three older
      children.
AB  - OBJECTIVE: To describe a pattern of abusive head injury in a series of children
      older than 4 years of age. METHODS: A hospital chart review of abused children
      with skull fractures from 1999 to 2001 was carried out. The clinical features,
      social background, and subsequent outcome and management are described. RESULTS:
      An 11-year-old girl and a pair of brothers of ages 7 and 9 were identified. The
      girl was attacked with a hammer during sleep by her stepmother, who committed
      suicide shortly afterwards. After craniotomy and intensive care, the child
      survived her multiple depressed fractures, intracranial bleeding, and brain
      contusion. Two brothers from a second family were attacked from behind with a
      hammer by their biological father, who was subsequently found to have undiagnosed
      schizophrenia. A depressed occipital fracture, without intracranial injury, was
      found in each child. The elder brother also had metacarpal fractures. Both
      children recovered without surgical intervention. CONCLUSION: A pattern of
      abusive head injury was described in older children with depressed skull
      fractures from blunt injury. The abusing parents were seriously mentally
      disturbed, and the abusive acts closely resembled child homicide.

PMID- 14637306
TI  - Connexin36 distribution in putative CO2-chemosensitive brainstem regions in rat.
AB  - Recent work from our laboratory has demonstrated that the gap junction proteins
      connexin26 (Cx26) and connexin32 (Cx32) are expressed in neurons in putative CO2
      chemosensitive brainstem regions in both neonatal and adult rats. Whether the
      recently identified neuron-specific gap junction protein connexin36 (Cx36) is
      also present in these brainstem regions remains to be determined. Therefore, in
      the current experiments, immunoblot and immunohistochemical protocols were used
      to investigate the regional distribution and cellular localization of Cx36 in
      putative CO2-chemosensitive brainstem regions in both neonatal and adult rats.
      Immunoblot analyses revealed Cx36 expression in putative CO2-chemosensitive
      brainstem regions in each of the age groups examined, although both regional and
      developmental differences in the relative expression levels were detected.
      Immunohistochemical analyses confirmed Cx36 expression in neurons in each of the
      putative CO2-chemosensitive brainstem regions and revealed both somal and
      dendritic labeling patterns. These findings provide additional morphological
      evidence supporting the potential for gap junctional communication in these
      regions in both neonatal and adult rats. We propose that the gap junction protein
      Cx36 also contributes to the neuroanatomical substrate for gap junctional
      communication, which is hypothesized to play a role in central CO2
      chemoreception.

PMID- 14637307
TI  - Vascular reactivity to norepinephrine and acetylcholine after chronic
      intermittent hypoxia in mice.
AB  - This study assessed the early vascular reactivity changes in mice after exposure
      to 14 days intermittent hypoxia (IH) with active or inactive sympathetic nervous
      system (SNS). Hindquarters of mice exposed to 14 days of IH, sham exposed mice or
      unhandled mice were perfused at constant flow with Krebs-Albumin (5%). Changes in
      perfusion pressure were assessed after injection of several doses of
      norepinephrine in anaesthetized mice (active SNS) or in euthanized mice (inactive
      SNS). Response to several doses of acetylcholine was recorded after
      precontraction of hindquarter vascular bed by methoxamine in euthanized mice.
      Vasoconstrictor response was increased after IH for high dose of NE (50 microg)
      in euthanized mice and for all doses of NE (2-10-50 microg) in anaesthetized
      mice, but no change in vasodilatation was observed. These findings suggest that
      14 days of IH altered vascular reactivity of mice hindquarter in an early
      pattern. Vasoconstriction was enhanced, particularly with active SNS, while there
      was no dysfunction of endothelium-relaxation.

PMID- 14637308
TI  - Effects of expiratory pressure on nitric oxide in exhaled breath. Is exhaled
      nitric oxide really unaffected by pressure?
AB  - The measurements of exhaled nitric oxide (ENO) concentrations in several previous
      reports have been quite disparate but the cause of this variability is unclear.
      In the present study, we have attempted to elucidate the effects of expiratory
      pressure upon ENO values by taking measurements at pressures ranging from 2 to 10
      cmH2O in control subjects and in both smokers and asthmatics. Differences in ENO
      concentrations (delta pNO) were then estimated and the concentration levels were
      found to increase with elevated expiratory pressure levels in both the control
      volunteers and in the asthmatics (under 2 and 3 L/min flow rates). These results
      indicate that changes in expiratory pressure indeed affect ENO concentrations.
      The measurement of ENO concentrations in human patients must therefore be
      undertaken using standard procedures that must incorporate expiratory pressure
      levels in order to properly interpret ENO values.

PMID- 14637309
TI  - Global BOLD MRI changes to ventilatory challenges in congenital central
      hypoventilation syndrome.
AB  - We evaluated global blood oxygen level dependent (BOLD) signal changes in gray
      and white matter in 14 congenital central hypoventilation syndrome (CCHS) and 14
      control subjects. One baseline image series with room air and three series with
      30 s room air followed by 120 s hypercapnia (5% CO2/95% O2), hypoxia (15% O2/85%
      N2) or hyperoxia (100% O2) were collected. Hypercapnia and hyperoxia raised, and
      hypoxia lowered gray and white matter global signal in both groups, with smaller
      changes in white matter. Signal changes in CCHS cases were lower than control
      subjects for hypercapnia in gray and white matter, slightly more-enhanced in
      hypoxia, and, except for initial transient responses, were nearly comparable
      during hyperoxia. Initial signal rate or pattern changes emerged in all three
      challenges in gray or white matter in control, but not CCHS cases. Neural or
      vascular mechanisms mediate perfusion differently in CCHS; the aberrant initial
      transient responses may reflect deficiencies in rapidly-varying physiologic
      interactions in the syndrome.

PMID- 14637310
TI  - Site of inflammation influences site of hyperresponsiveness in experimental
      asthma.
AB  - BACKGROUND: Our recently developed murine asthma model is capable of inducing
      airway-specific chronic inflammatory changes and remodeling, features of human
      asthma commonly missing in conventional animal models. OBJECTIVES: To validate
      this model by site-specific physiological evaluation of hyperresponsiveness.
      METHODS: Non-sensitized and sensitized mice received either short-term
      uncontrolled or long-term controlled low-level exposures to aerosolized ovalbumin
      (OVA). Respiratory impedance (Zrs) was measured in response to increasing doses
      of methacholine (Mch). The constant-phase model was fitted to Zrs spectra to
      determine the specific site of hyperresponsiveness. RESULTS: Sensitized acutely
      exposed mice had significantly increased tissue damping (G), tissue elastance (H)
      and hysteresivity (eta) in response to Mch, but no significant increase in airway
      resistance (Raw), indicating tissue-specific hyperresponsiveness. In contrast,
      sensitized chronically exposed mice had significantly elevated Raw at all
      concentrations of Mch but no increases in G, H or eta indicating airway-specific
      hyperresponsiveness. CONCLUSIONS: Chronic inhalational exposure of sensitized
      mice to low-mass concentrations of OVA induces airway-specific
      hyperresponsiveness.

PMID- 14637311
TI  - Effect of the respiratory-related bronchial rhythmic constriction on alveolar
      ventilation in the dog.
AB  - The middle-sized bronchus constricts during mid-inspiration through early
      expiration. The purpose of this study was to elucidate the physiological role of
      this respiratory-related bronchial rhythmic constriction (RRBRC). The following
      parameters were measured in 12 decerebrated and paralyzed dogs: pressure from a
      balloon-tipped catheter in the fifth-generation bronchus (to reveal RRBRC),
      efferent neurogram from C(5) phrenic, and ventilatory flow and volume. We found a
      small but significant reduction of peak expiratory flow of mechanical ventilation
      during RRBRC. During bilateral vagal cold block, RRBRC was simulated by
      intermittent electric stimulation of vagal fibers distal to the cold block. This
      stimulus evoked a decrease in peak expiratory flow and in Pa(CO2) (approximately
      1.5 mmHg). After vagal warming, mechanical ventilation was terminated, and blood
      gases were maintained normal by extracorporeal oxygenation. During each RRBRC
      ventilatory volume decreased by approximately 3 ml. The changes in gas volume and
      RRBRC disappeared after bilateral vagotomy. These findings support the concept
      that the physiological role of RRBRC is to facilitate alveolar gas exchange by
      reducing expiratory flow, anatomical dead space, or both.

PMID- 14637312
TI  - Paranatal oxygen consumption and respiratory frequency in the Laysan Albatross.
AB  - The oxygen consumption and respiratory frequency of Laysan Albatross eggs were
      measured during the different phases of pipping (paranatal period) and in
      hatchlings. The initial phase of pipping--penetration of the aircell of the egg
      by the embryonic beak--coincided with the beginning of pulmonary ventilation, the
      embryo rebreathing aircell gas, but it did not result in a statistically
      significant increase in oxygen consumption. The second phase of pipping--star
      fracture of the shell (external pipping)--was the shortest (25 h) of the three
      phases of pipping, and it did not result in a significant increase in either
      oxygen consumption or respiratory frequency. The longest phase of pipping (65 h)-
      the pip-hole phase--represented 54% of the total duration of pipping, and it was
      accompanied by significant increases in oxygen consumption and respiratory
      frequency. When the eggs hatched, the oxygen consumption increased further but
      respiratory frequency diminished significantly. It was calculated that the
      paranatal period, which represented 7.9% of the total incubation period of the
      egg, accounted for 37.2% of the total oxygen consumption of the egg.

PMID- 14637313
TI  - Role of aquaporin and sodium channel in pleural water movement.
AB  - The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on
      pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or
      isosmolar fluid was infused into the pleural space in anesthetized wildtype and
      AQP1 null mice. Pleural fluid was sampled at specified times to quantify the
      osmolality and volume. The sodium channel activator terbutaline increased
      isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride
      decreased it by 15%, but had no effect on osmotically driven water transport.
      AQP1 deletion significantly decreased osmotic water transport in pleural space by
      twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with
      dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous
      injection of HgCl2 decreased osmotic pleural water movement by 43%. These results
      provided evidence for a role of a sodium channel in pleural fluid absorption;
      AQP1 plays a major role in osmotic liquid transport but it does not affect
      isosmolar fluid clearance.

PMID- 14637315
TI  - What is eupnea.
AB  - Respiratory neuronal networks in vertebrates appear to be able to generate a
      variety of rhythmic patterns in vivo, leading to the biological diversity of
      eupneic patterns as well as to life-threatening dyspneic patterns. Eupnea is best
      viewed as the collection of respiratory strategies preventing potential dyspneas,
      the major (and perhaps the only) criterion for a definition being that eupnea
      allows survival. Specific criteria can then be derived from the physiological
      identification of neurobiological mechanisms underlying identified dyspneic
      patterns, by exaggerating (pro-dyspneic mechanisms) or suppressing them (anti
      dyspneic mechanisms). Because eupnea is vital, and one of the major targets of
      evolutionary pressure, identification of dyspnea-related neuronal systems seems
      to be important to understand the normal biological organization of the
      respiratory neuronal system.

PMID- 14637316
TI  - Defining eupnea.
AB  - To describe a pattern of rhythmic activity as "breathing" or "respiration"
      inevitably leads to the conclusion that this rhythmic activity is "normal" or
      "eupneic". Initially, it must be noted that, by strictest definition, "eupnea"
      can only be applied to "breathing" in an unanesthetized preparation. Any
      experimental perturbation, including anesthesia, changes eupnea, primarily by
      reducing the frequency of "breathing". However, a "eupneic pattern", in terms of
      the pattern of airflow of individual breaths, remains. Also remaining are
      patterns of neural and neuronal activities which are characteristic of individual
      breaths of eupnea. In this commentary, we consider these patterns of activities,
      which define a eupneic pattern and contrast these with patterns during apneusis
      and gasping. It has long been recognized that these three different patterns of
      "respiratory activity", eupnea, apneusis and gasping, can be generated in
      preparations in which all of the central nervous system has been removed,
      exclusive of the brainstem and spinal cord.

PMID- 14637318
TI  - Commentary on the definition of eupnea and gasping.
AB  - Despite clear qualitative differences, it has proven difficult to identify
      criteria that reliably differentiate eupnea and gasping--particularly when
      multiple species or experimental preparations are considered. From a motor
      control perspective, this is unsurprising. Three organizational rules are common
      to nearly all rhythmic activities: (1) the basic rhythm is produced by a small
      network of cells, (2) the activity of this network in isolation often differs
      dramatically from the behavior of the whole animal, and (3) the rhythmogenic
      networks responsible for related behaviors are not fixed and independent but
      dynamically modifiable and overlapping. In this context, it becomes clear that
      the definition of a particular pattern and the investigation of the mechanisms
      underlying its production are inseparable. Rather than attempting to rigidly
      apply criteria developed using any one experimental preparation, the
      classification of respiratory patterns must evolve alongside our understanding of
      how each pattern is produced-a process that is only aided by investigations using
      a variety of experimental preparations.

PMID- 14637317
TI  - A commentary on eupnoea and gasping.
AB  - This commentary discusses the differences between patterns of bursting activity
      recorded from the phrenic nerves of different species, in several experimental
      preparations and under differing conditions. The spectrum of bursting activity
      patterns varies from that termed eupnoic to that termed gasping. Taking the
      pattern of activity recorded in the least reduced preparation as a standard for
      normality, i.e. eupnoea, consideration is given to the possible factors affecting
      the pattern of bursting activity in progressively reduced preparations. An
      examination of the conditions of these preparations leads to the conclusion that
      tissue gas exchange is a major determinant of bursting pattern, and consideration
      is given to the possible differences in respiratory rhythm generation that can be
      inferred from these different patterns.

PMID- 14637319
TI  - Commentary on eupneic breathing patterns and gasping.
AB  - The term "eupneic activity pattern" is a trivial phenotypical description of a
      particular activity pattern in respiratory nerves as recorded under in vivo like
      experimental conditions. This term is, however, inadequate, because Eupnea
      describes a behavioral breathing performance that is trouble-free occurring
      without conscious effort. Obviously, the term "eupneic activity pattern" is meant
      to describe a neural activity that is normal and comparable with quiet breathing
      conditions. The various in vivo, in situ and in vitro preparations all generate
      their specific "normal" activity patterns, when the conditions are undisturbed.
      The commentary describes some of the numerous reasons why such normal activity
      patterns must be different in the various preparations without indicating their
      pathological operation. The conclusion is that special considerations are
      necessary for any extension of the in vitro and in situ findings into in vivo
      situations, because the capacity of the respiratory network is greatly reduced
      and thus not comparable with conditions leading to "eupneic breathing" in the
      fully intact animal.

PMID- 14637320
TI  - Determinants of nutritional behaviour: a multitude of levers for successful
      intervention?
AB  - Nutritional behaviour is framed by biological, anthropological, economic,
      psychological, socio-cultural, and home economics related determinants and it is
      shaped by the individual situation. From a public health point of view, the
      outcome is often unsatisfactory, because it is associated with preventable cases
      of various diseases. This situation evoked the founding of the German Association
      for Nutritional Behaviour (Arbeitsgemeinschaft Ernahrungsverhalten, AGEV) which
      celebrated its 25th anniversary within the scope of the 10th Food Choice
      Conference in the summer of 2002 with a plenary session on 'Sensible policies for
      nutrition and life-style intervention'. One might assume that the many
      determinants of nutritional behaviour provide a whole set of means to intervene
      into people's food choices. But closer deliberations make clear that there are
      two important aspects that tend to hinder dietary changes: on the one hand,
      nutritional behaviour is characterized by many conflicts of its related
      determinants. In order to cope with them, people develop individual guiding
      strategies for food choice situations which are quite stable as soon as they
      proved their suitability. On the other hand, any dietary modification leads to
      certain gains (like increased health), but losses, as well (like decreased
      palatability). Thus, a sustainable change can only be expected, if its gains are
      evaluated higher than its losses. These aspects need to be carefully considered
      when designing nutrition and life-style related intervention concepts.

PMID- 14637321
TI  - Impact of nutrition behaviour research on nutrition programmes and nutrition
      policy.
AB  - Development of a society is interrelated with research. Innovation in food and
      nutritional sciences enable citizens to live in conditions of food security.
      Current dietary goals can be reached by understanding the biopsychosocial
      background of human nutrition behaviour. Examples of diffusion of such findings
      into practice are presented with emphasis on Germany and the activities of AGEV
      (the Working Association of Nutritional Behaviour), which was founded 25 years
      ago. Nutrition behaviour research should strengthen the focus on practical
      applications of its findings, since the prevalence of nutrition-related problems,
      like obesity in children and the estrangement on food and nutrition, is
      increasing.

PMID- 14637322
TI  - Dietary changes in Finland--success stories and future challenges.
AB  - The paper describes dietary changes and related nutrition policies and
      interventions in Finland since the 1960s. Dietary changes are interpreted from
      the lifestyle perspective, in which food consumption patterns are assumed to be
      formed by the interplay of individual choices and structural chances, such as
      socioeconomic and cultural conditions. Finland can demonstrate a success story
      when it comes to decreased use of dairy fats and increased use of vegetables and
      fruit. However, the prevalence of overweight has increased. Nutrition policies
      and interventions together with sociocultural factors have supported the shift
      towards healthy nutrition. The same factors have promoted overweight, as well.

PMID- 14637323
TI  - Experiences with the Norwegian nutrition policy.
AB  - Norwegian nutrition policy has received considerable attention. The
      distinguishing feature is its 'structural' orientation, i.e. towards production
      and market regulation, as opposed to individual, information-based strategies.
      This was possible first of all because of distinctive Norwegian political
      traditions, with a heavily regulated agricultural sector, combined with a welfare
      policy tradition emphasising influence on other sectors. While the
      institutionalisation of the Norwegian nutrition policy has been important for its
      political legitimacy and visibility, the paper discusses how this has also
      represented a challenge when problems and policy goals are to be altered.

PMID- 14637324
TI  - Exploring the occurrence and nature of comparison of one's own perceived dietary
      fat intake to that of self-selected others.
AB  - Lack of awareness of personal dietary fat intake is associated with a low
      motivation to change to a diet lower in fat. An optimistic bias in the comparison
      of one's own fat intake to that of others is associated with this lack of
      awareness. Insight into the way people make interpersonal comparisons related to
      fat intake may contribute to a better understanding of dietary intake and its
      determinants. Such insight may provide suggestions for nutrition education
      interventions aimed at increasing awareness and intention to change. The present
      study explores interpersonal comparisons involved in evaluating personal dietary
      fat intake. One hundred and eighty-nine respondents participated in structured
      telephone interviews. The respondents reported that they use interpersonal
      comparison information related to fat intake to some extent and that they mostly
      compare themselves with close relatives and friends. Respondents who intended to
      change to a lower fat diet and the younger ones were more likely to compare
      themselves with others. Comparison targets were perceived to eat small, as well
      as large or average amounts of fat, which may indicate that people use positive
      as well as negative role models for making interpersonal comparisons in terms of
      dietary fat intake.

PMID- 14637325
TI  - Evaluation of strategies used by family food preparers to influence healthy
      eating.
AB  - The family may exert powerful influence on family members' eating habits, though
      there is very little conclusive literature regarding the specific mechanisms. The
      authors investigated how often family food preparers use particular strategies to
      encourage their families to eat more healthily and then related these strategies
      to healthy eating outcomes in children. We identified significant differences in
      strategy use between family age subgroups, and we included strategy types in
      multiple linear regression models to predict differences in families with
      children. Results indicate that discussing healthy food related to 'Pressuring'
      strategies and discussing healthy eating related to 'Feeling and looking good'
      predicted healthy eating outcomes. Findings have implications for designing
      dietary interventions to have the largest public health impact.

PMID- 14637326
TI  - The effect of oral and product temperature on the perception of flavor and
      texture attributes of semi-solids.
AB  - This study examined the effect of oral and product temperature on the perception
      of texture and flavor attributes. A trained panel assessed 21 texture and flavor
      attributes in one high-fat and one low-fat product of two semi-solids: custard
      dessert and mayonnaise. The products were evaluated at 10, 22 or 35 degrees C in
      combination with oral temperatures of 27, 35 and 43 degrees C. Results showed
      that modulation of product and oral temperature had significant effects on a
      number of attributes. Flavor intensities, melting mouth feel, and fat after feel
      increased, while subjective thickness decreased with increasing product
      temperature. Neither product- nor oral temperature had an effect on over-all
      creaminess. Oral temperature affected a number of mouth feel attributes: melting,
      heterogeneous and smooth. Furthermore, large differences existed in ratings
      between the high- and low-fat products of custard and mayonnaise, and they were
      more prominent in mayonnaise. We conclude that the effect of oral temperature on
      the perception of sensory attributes in semi-solids was small, but present, while
      the product temperatures influenced the ratings greatly.

PMID- 14637327
TI  - Habituation of salivation and motivated responding for food in children.
AB  - Repeated presentation of food cues results in habituation in adults, as
      demonstrated by a decrement in salivary responding that is reversed by presenting
      a new food cue in adults. Food reinforced behavior in animals shows the same
      pattern of responding, with a decrease in responding to obtain the food, followed
      by a recovery of responding when a new food is presented. The present study
      assessed whether children would show the same pattern of a decrement of food
      reinforced responding followed by recovery of responding when a new food is
      presented for both salivation and food reinforcement tasks. Subjects were
      assigned to one of two groups that differed in the trial that the new food
      stimulus was presented to ensure recovery was specific to the introduction of the
      new food stimulus. In the salivation task, subjects were provided repeated
      olfactory presentations of a cheeseburger with apple pie as the new food
      stimulus, while in the food reinforcement task subjects worked for the
      opportunity to consume a cheeseburger, followed by the opportunity to work for
      consumption of apple pie. Subjects in both groups showed a decrement in salivary
      and food reinforced responding to repeated food cues followed by immediate
      recovery of responding on the trial when a new food was presented. Subjects
      increased their energy intake by over 30% in the food reinforcement task when a
      new food was presented. These results are consistent with the general process
      theory of motivation that suggests that changes in food reinforced responding may
      be due in part to habituation.

PMID- 14637328
TI  - The effect of self-initiated weight-loss dieting on working memory: the role of
      preoccupying cognitions.
AB  - This study investigated the effects of weight loss dieting on the components of
      working memory and the extent to which these effects were mediated by
      preoccupying cognitions concerning food, diet and body shape. A dual task
      paradigm was used in which dieters (n=20) and non-dieters (n=20) completed mental
      arithmetic problems concurrently with suppression tasks designed to engage the
      central executive, phonological loop, and visuo-spatial sketchpad components of
      working memory. In addition, tasks reflecting the articulatory control process
      and phonological store sub-components of the phonological loop were also
      completed. Results showed that dieters performed more poorly on measures of the
      central executive and the phonological loop compared with non-dieters. Dieters
      reported higher levels of preoccupying cognitions which mediated the relationship
      between dieting status and functioning of the central executive and phonological
      loop, and the phonological store in particular.

PMID- 14637329
TI  - Perceived barriers to consumption of fish among Norwegian women.
AB  - This study aimed to characterize constraints on consumption of fish perceived by
      consumers in Norway. A random sample of Norwegian women aged 45-69 years answered
      a self-administered mail questionnaire in 1996 about eating habits, perceived
      barriers to fish consumption, socioeconomic status, and questions related to
      health. Altogether, 9407 women answered the questionnaire (response rate: 52.5%).
      Data were analyzed by means of logistic regression. Limited supply of fish
      products that satisfy children's wishes reduce at-home fish consumption. People
      with health problems and those who wish to lose weight are dissatisfied with the
      range of products offered in the marketplace. Satisfaction with quality and
      availability of wild lean codfish, especially in inland regions, is lower than
      for aqua-cultured fat salmon. Neither income nor education or health factors were
      significantly associated with consumption levels among those who would like to
      eat more fish. Higher education and income were associated with increased
      dissatisfaction about fish consumption, but also with reduced perception of most
      barriers. It is concluded that improvements in the supply of high-quality fresh
      and processed fish products that satisfy (a) children's wishes, (b) health
      oriented family members, and (c) convenience-oriented consumers, will
      significantly increase at-home consumption of fish.

PMID- 14637330
TI  - Do economic constraints encourage the selection of energy dense diets?
AB  - Economic constraints, by inducing the selection of low cost energy dense diets,
      could indirectly be responsible for the high prevalence of obesity in low socio
      economic status groups. Diet optimisation by linear programming was used to test
      this hypothesis, by examining the relationship between the cost and the energy
      density (ED) of modelled diets. Models were developed that minimized the
      departure from the mean adult French diet estimated from a cross-sectional
      dietary survey. Palatability constraints were introduced into all models. The
      impacts of cost on ED and of ED on cost were explored by introducing and
      strengthening first a constraint on cost and then a constraint on ED. Forcing the
      cost of the linear programming diets to decrease induced a strong increase in
      their EDs. In contrast, forcing the ED to increase induced only a moderate
      decrease in diet costs. These results suggest that, although an energy dense diet
      can be selected at a relatively high cost, when cost is not influencing food
      choices, an energy dense diet will be preferentially selected to maintain
      habitual French dietary patterns when the budget for food is low. This supports
      the hypothesis that economic constraints play a role in the high prevalence of
      obesity in low-income people.

PMID- 14637331
TI  - Profiling taste-motivated segments.
AB  - Early adopters of unfamiliar, but nutritious foods can do so because of a
      combination of taste-motivations and health-motivations. Yet because taste can
      provide an enduring motivation for dietary change, profiling the taste-motivated
      segment of a particular food might prove useful in identifying and stimulating
      adoption among similar predisposed segments. This manuscript describes a basic
      qualitative and quantitative procedure--in the context of soy consumption--that
      can be used to begin profiling taste-motivated segments of a particular food. A
      survey of 606 North Americans indicates that when contrasted to health-motivated
      consumers of soy, taste-motivated consumers were more likely to claim they are
      opinion-leaders who live with (or who are) great cooks, and they were more likely
      to exhibit other behaviors associated with food appreciation, such as dining out
      and wine consumption. In light of these findings, instead of encouraging people
      to eat soy solely for health reasons, a more productive method may be to target
      those who are more likely to prefer it for taste-motivated reasons. This same
      method has potential for more effectively promoting the consumption of fruits and
      vegetables or the consumption of genetically enhanced foods among predisposed
      taste-motivated segments.

PMID- 14637332
TI  - Breakfast reduces declines in attention and memory over the morning in
      schoolchildren.
AB  - Twenty-nine schoolchildren were tested throughout the morning on 4 successive
      days, having a different breakfast each day (either of the cereals Cheerios or
      Shreddies, glucose drink or No breakfast). A series of computerised tests of
      attention, working memory and episodic secondary memory was conducted prior to
      breakfast and again 30, 90, 150 and 210 min later. The glucose drink and No
      breakfast conditions were followed by declines in attention and memory, but the
      declines were significantly reduced in the two cereal conditions. This study
      provides objective evidence that a typical breakfast of cereal rich in complex
      carbohydrates can help maintain mental performance over the morning.

PMID- 14637333
TI  - Interaction between natural motivational systems and those which respond to drugs
      of abuse.
AB  - Recent results are reviewed from neural and behavioral comparisons and
      interactions of salt appetite induced by multiple depletions and sensitization of
      the psychostimulant effects of amphetamine.

PMID- 14637334
TI  - Integration of hypothalamic feeding and metabolic signals: focus on neuropeptide
      Y.
AB  - Research is reviewed on effects of neuropeptide Y (NPY) on energy substrate
      utilization and central interactions among NPY, serotonin and urocortin,
      particularly in neurons of the paraventricular nucleus of the hypothalamus.

PMID- 14637335
TI  - Reductive degradation of nitrobenzene in aqueous solution by zero-valent iron.
AB  - The reductive degradation of nitrobenzene (NB) by zero-valent iron was
      investigated. Experimental results showed that the degradation of NB was
      influenced by pH and NB concentration. The optimum pH value was found to be 3.0
      for the reductive degradation of NB in the tested pH ranges of 3.0-12.0. The
      formation rate of aniline, a major reductive product of NB, followed zero-order
      kinetics at various pH levels. Furthermore, GC/MS analysis showed that aniline,
      azobenzene and azoxybenzene were the reductive products of NB by zero-valent
      iron. With the analysis of the products with GC/MS and FTIR, possible reductive
      pathways of NB by zero-valent iron were suggested.

PMID- 14637336
TI  - Hydrocarbon pollution fixed to combined sewer sediment: a case study in Paris.
AB  - Over a period of two years (2000-2001), sediment samples were extracted from 40
      silt traps (STs) spread through the combined sewer system of Paris. All sediment
      samples were analysed for physico-chemical parameters (pH, organic matter
      content, grain size distribution), with total hydrocarbons (THs) and 16
      polycyclic aromatic hydrocarbons (PAHs) selected from the priority list of the US
      EPA. The two main objectives of the study were (1) to determine the hydrocarbon
      contamination levels in the sediments of the Paris combined sewer system and (2)
      to investigate the PAH fingerprints in order to assess their spatial variability
      and to elucidate the PAH origins. The results show that there is some important
      inter-site and intra-site variations in hydrocarbon contents. Despite this
      variability, TH and PAH contamination levels (50th percentile) in the Parisian
      sewer sediment are estimated at 530 and 18 microg g(-1), respectively. The
      investigation of the aromatic compound distributions in all of the 40 STs has
      underlined that there is, at the Paris sewer system scale, a homogeneous PAH
      background pollution. Moreover, the study of the PAH fingerprints, using specific
      ratios, suggests the predominance of a pyrolytic origin for those PAHs fixed to
      the sewer sediment.

PMID- 14637337
TI  - Estimating the emission source reduction of PM10 in central Taiwan.
AB  - Three theoretical parent frequency distributions; lognormal, Weibull and gamma
      were used to fit the complete set of PM10 data in central Taiwan. The gamma
      distribution is the best one to represent the performance of high PM10
      concentrations. However, the parent distribution sometimes diverges in predicting
      the high PM10 concentrations. Therefore, two predicting methods, Method I: two
      parameter exponential distribution and Method II: asymptotic distribution of
      extreme value, were used to fit the high PM10 concentration distributions more
      correctly. The results fitted by the two-parameter exponential distribution are
      better matched with the actual high PM10 data than that by the parent
      distributions. Both of the predicting methods can successfully predict the return
      period and exceedances over a critical concentration in the future year.
      Moreover, the estimated emission source reductions of PM10 required to meet the
      air quality standard by Method I and Method II are very close. The estimated
      emission source reductions of PM10 range from 34% to 48% in central Taiwan.

PMID- 14637338
TI  - Study on hydrogen production with hysteresis in UASB.
AB  - This paper uses a 10-l UASB (upflow anaerobic sludge blanket) bench-scale reactor
      to treat the esterification wastewater of a polyethylene terephthalate
      manufacturing plant. Two organic loading rates are used to evaluate the effect on
      H2 production of temperature gradually step-down and step-up in the range of 11
      25 degrees C. Experimental results show that H2 production is positively related
      to temperature. H2 production increases with temperature at the higher organic
      loading rate (4.5 kg COD m(-3)d(-1)). However, the H2 produced does not go back
      to its original concentration but rather follows a hysteresis curve. This
      hysteresis also occurs in the corresponding concentrations of COD, acetate,
      propionate and butyrate. As in the H2 profiles, these parameter curves return
      clockwise during the temperature step-up. At the lower organic loading rate (2.2
      kg COD m(-3)d(-1)), no obvious hysteresis is observed for H2 curve. The pattern
      of other parameters, except for the propionate, returns counterclockwise
      resulting in the hysteresis phenomena.

PMID- 14637339
TI  - Effect of Fe0 quantity on the efficiency of integrated microbial-Fe0 treatment
      processes.
AB  - Batch experiments were conducted with different reaction systems to investigate
      how the treatment efficiency of integrated microbial-Fe0 processes is affected by
      the amount of Fe0 added. Abiotic experiments with hexavalent chromium and carbon
      tetrachloride mixtures corroborated that different pollutants could compete for
      reactive sites on the iron surface, which would hinder specific degradation rates
      when the available Fe0 surface area is relatively small (e.g., 11 m(2) l(-1)). In
      such cases, reductive precipitation of chromium could occlude reactive sites and
      significantly inhibit removal efficiency. Microbial participation in the cleanup
      process was also influenced by the amount of Fe0 added. Increasing the Fe0 dose
      (and thus the available surface area) had a stimulatory effect possibly due to a
      higher production of cathodic H2, which can be used as electron donor for
      reductive biotransformation of many pollutants. However, high Fe0 doses had an
      inhibitory effect due to a corrosion-induced increase in pH beyond the optimum
      range of the bacteria. This suggest that there may be a system-specific, optimum
      quantity of Fe0 that satisfies availability requirements to preclude contaminant
      competition for reactive sites and biological requirements for H2 production
      while minimizing inhibitory increases in pH. Results also confirmed extensive RDX
      mineralization in bioaugmented (but not in abiotic) Fe0 systems, and support the
      notion that permeable reactive iron barriers performance might be enhanced by the
      participation of some microorganisms.

PMID- 14637340
TI  - Removal of aqueous-phase polynuclear aromatic hydrocarbons using aspen wood
      fibers.
AB  - Roadway runoff derived polynuclear aromatic hydrocarbons (PAHs) impact the
      quality of surface and ground water. Inexpensive aspen wood fibers have been
      investigated as a means to remove dissolved PAH under laboratory conditions. Our
      isotherm experiments demonstrated that the uptake of naphthalene, fluorene,
      anthracene, and pyrene required up to 12.5 days to reach equilibrium. Aspen wood
      water sorption coefficients, Kww, were linearly correlated to octanol-water
      partition coefficients and the molecular weight of the studied PAH compounds. The
      correlation between Kww and molecular weight was the most significant. Column
      experiments were carried out to study the sorption and desorption of fluorene,
      anthracene, and pyrene under dynamic conditions. The results indicate linear
      sorption, but non-linear desorption behavior. The degree of desorption was
      inversely correlated to a compound's hydrophobicity. Flow interruption
      experiments showed that sorption and desorption was rate limited. A mass balance
      of the sorption and desorption tests indicated that sorptive uptake exceeded
      desorptive release over a given number of pore volumes. Further, absolute mass
      removal efficiency increased with the molecular weight and hydrophobicity of the
      PAH compound. Batch and column studies demonstrated that aspen wood has the
      potential to become an effective remedial agent for PAH in stormwater runoff or
      other PAH contaminated waters.

PMID- 14637341
TI  - Remediating dicamba-contaminated water with zerovalent iron.
AB  - Dicamba (3,6-dichloro-2-methoxybenzoicacid) is a highly mobile pre- and post
      emergence herbicide that has been detected in ground water. We determined the
      potential of zerovalent iron (Fe0) to remediate water contaminated with dicamba
      and its common biological degradation product, 3,6-dichlorosalicylic acid (DCSA).
      Mixing an aqueous solution of 100 microM dicamba with 1.5% Fe0 (w/v) resulted in
      80% loss of dicamba within 12 h. Solvent extraction of the Fe0 revealed that
      dicamba removal was primarily through adsorption; however when the Fe0 was
      augmented with Al or Fe(III) salts, dicamba was dechlorinated to an unidentified
      degradation product. In contrast to dicamba, Fe0 treatment of DCSA resulted in
      removal with some dechlorination observed. When DCSA was treated with Fe0 plus Al
      or Fe(III) salts, destruction was 100%. Extracts of this Fe0 treatment contained
      the same HPLC degradation peak observed with the Fe0 + Al or Fe(III) salt
      treatment of dicamba. Molecular modeling suggests that differences in removal and
      dechlorination rates between dicamba and DCSA may be related to the type of
      coordination complex formed on the iron surface. Experiments with 14C-labeled
      dicamba confirmed that Fe-adsorbed dicamba residues are available for subsequent
      biological mineralization (11% after 125 d). These results indicate that Fe0
      could be potentially used to treat dicamba and DCSA-contaminated water.

PMID- 14637342
TI  - Monitoring the sonochemical degradation of phthalate esters in water using solid
      phase microextraction.
AB  - The sonochemical degradation of aqueous solutions containing low concentrations
      of six phthalate esters at an ultrasonic frequency of 80 kHz has been
      investigated. Ultrasonic treatment was found capable of removing the four higher
      molecular mass phthalates (di-n-butyl phthalate, butylbenzyl phthalate, di-(2
      ethylhexyl) phthalate and di-n-octyl phthalate) within 30-60 min of irradiation.
      The rest (dimethyl phthalate and diethyl phthalate) were more recalcitrant and
      nearly complete removal could be achieved only after prolonged irradiation times.
      The relative reactivity of phthalates was explained in terms of their
      hydrophobicity. Experiments were carried out at an overall initial phthalate
      concentration of 240 microg l(-1), values of electric power of 75 and 150 W,
      temperatures of 21 and 50 degrees C and in the presence of NaCl to study the
      effect of various operating conditions on degradation. Solid-phase
      microextraction (SPME) coupled with GC-MS proved to be a powerful analytical tool
      to monitor the sonochemical degradation of phthalate esters at low microg l(-1)
      concentration levels, minimising the risk of secondary contamination during
      sample preparation, a major parameter to consider during phthalates analysis. The
      advantages as well as disadvantages of using SPME are also highlighted.

PMID- 14637343
TI  - Factors influencing the preparation of supported iron oxide in fluidized-bed
      crystallization.
AB  - Our previous work applied a novel supported iron oxyhydroxide (FeOOH) catalyst to
      effectively treat benzoic acid by hydrogen peroxide. The FeOOH catalyst was
      prepared via the oxidation of Fe2+ by H2O2 in the acidic condition using a
      fluidized-bed crystallization reactor. The major components coated on the surface
      were identified as amorphous FeOOH and gamma-FeOOH. In terms of the
      crystallization conditions of FeOOH, some parameters including the operational
      pH, superficial velocity, specific iron loading, and influent H2O2 concentration
      were investigated to quantify their effects on the crystallization efficiency.
      All these parameters were found to significantly influence the crystallization
      efficiency. Two types of FeOOH catalysts were synthesized: FeOOH I was prepared
      at pH 3.5, and FeOOH II was formed by aging FeOOH I at pH 13. The percentages of
      surface amorphous FeOOH reduced from 70% to 30% after aging. The FeOOH II
      catalyst presented a higher reactivity toward H2O2 but lower stoichiometric
      efficiency in oxidizing benzoic acid than FeOOH I, similar to the result of the
      commercial goethite. Therefore, it is concluded that the crystalline property
      significantly affects the performance of catalytic oxidation.

PMID- 14637344
TI  - Heavy metal accumulation by Nicotiana glauca Graham in a solid waste disposal
      site.
AB  - Nicotiana glauca Graham, is the only perennial shrub growing in a solid waste
      contaminated site in the Negev desert of Israel. The concentration of heavy
      metals (Cu, Fe, Mn, Zn, Ni, Cd and Pb) in the upper soil layer was significantly
      higher (p<0.01) than in non-contaminated desert soil. In root and shoot of N.
      glauca, growing in the site, the concentration of Cu, Zn and Fe was significantly
      higher (p<0.05) than in plants of a non-contaminated site. In a controlled
      experiment, the concentrations of Zn and Cu in root of plants grown, in a mixture
      of contaminated and non-contaminated soil (1:1) was 9.5 and 4.7 higher than that
      of plants grown in non-contaminated soil, respectively. While Zn was accumulated
      in shoot of plants grown in contaminated soil (531 mgkg(-1)) in significantly
      higher concentration than in plants grown in non-contaminated soil (56 mgkg(-1)),
      no significant differences were found in Cu accumulation. Growth of N. glauca was
      inhibited on contaminated soil, but no other obvious stress symptoms were
      apparent. Therefore, long term experiments under controlled conditions are
      planned to study the mechanism of heavy metal tolerance and accumulation in N.
      glauca.

PMID- 14637345
TI  - Radioactive waste forms stabilized by ChemChar gasification: characterization and
      leaching behavior of cerium, thorium, protactinium, uranium, and neptunium.
AB  - The uses of a thermally reductive gasification process in conjunction with
      vitrification and cementation for the long-term disposal of low level radioactive
      materials have been investigated. gamma-ray spectroscopy was used for analysis of
      carrier-free protactinium-233 and neptunium-239 and a stoichiometric amount of
      cerium (observed cerium-141) subsequent to gasification and leaching, up to 48
      days. High resolution ICP-MS was used to analyze the cerium, thorium, and uranium
      from 46 to 438 days of leaching. Leaching procedures followed the guidance of
      ASTM Procedure C 1220-92, Standard Test Method for Static Leaching of Monolithic
      Waste Forms for Disposal of Radioactive Waste. The combination of the thermally
      reductive pretreatment, vitrification and cementation produced a highly non
      leachable form suitable for long-term disposal of cerium, thorium, protactinium,
      uranium, and neptunium.

PMID- 14637346
TI  - Lentinula edodes removes phenols from olive-mill wastewater: impact on durum
      wheat (Triticum durum Desf.) germinability.
AB  - Olive-mill wastewater (OMW) exhibits highly phytotoxic properties, mainly due to
      phenols. A valuable option for OMW disposal is its agricultural use provided that
      phytotoxic effects are removed. The present investigation was aimed at evaluating
      the efficacy of the lignin-degrading fungus Lentinula edodes in achieving OMW
      detoxification. Germinability experiments on durum wheat showed that OMW
      phytotoxicity was significantly reduced by L. edodes cultures. Germinability on
      undiluted and twofold diluted OMW from fungal cultures was 34+/-5% and 57+/-6%,
      respectively, while on related incubation controls it was almost completely
      suppressed. These results suggest that fungal cultures of L. edodes would
      decrease the phytotoxicity of this waste.

PMID- 14637347
TI  - Two-dimensional model for soil electrokinetic remediation of heavy metals.
      Application to a copper spiked kaolin.
AB  - A two-dimensional numerical model has been developed to simulate the
      electrokinetic remediation of soils contaminated with heavy metals and has been
      validated using laboratory experiments performed with a copper spiked kaolin. The
      model divides the soil into compartments in a Cartesian grid and a non
      conductivity barrier encloses the considered area. Basically, it consists in two
      main parts clearly distinguishable. The first part describes the electromigration
      phenomenon in the soil, which is represented by a set of electric resistors,
      following the Cartesian grid and using Kirchoff's laws of electricity to
      calculate the voltage drop distribution in the considered area. The second part
      describes the chemical equilibrium process between the heavy metal and the soil,
      assuming local equilibrium conditions within the compartments. A good agreement
      was obtained between the lab scale experimental assays and the model predictions.
      The model has also been used to examine the effect of the electrolyte
      neutralization within the scope of the acid-enhanced electrokinetic method. These
      simulations have foreseen problems related with the system evolution, which would
      not arise under one-dimensional geometries and are due to the changes of the
      potential distribution in the two-dimensional arrangement where some kind of
      short circuit arises, ultimately leading to a decrease of the system efficiency.

PMID- 14637348
TI  - Modelling of the acid-base properties of natural and synthetic adsorbent
      materials used for heavy metal removal from aqueous solutions.
AB  - In this paper a comparison about kinetic behaviour, acid-base properties and
      copper removal capacities was carried out between two different adsorbent
      materials used for heavy metal removal from aqueous solutions: an aminodiacetic
      chelating resin as commercial product (Lewatit TP207) and a lyophilised bacterial
      biomass of Sphaerotilus natans. The acid-base properties of a S. natans cell
      suspension were well described by simplified mechanistic models without
      electrostatic corrections considering two kinds of weakly acidic active sites. In
      particular the introduction of two-peak distribution function for the proton
      affinity constants allows a better representation of the experimental data
      reproducing the site heterogeneity. A priori knowledge about resin functional
      groups (aminodiacetic groups) is the base for preliminary simulations of
      titration curve assuming a Donnan gel structure for the resin phase considered as
      a concentrated aqueous solution of aminodiacetic acid (ADA). Departures from
      experimental and simulated data can be interpreted by considering the
      heterogeneity of the functional groups and the effect of ionic concentration in
      the resin phase. Two-site continuous model describes adequately the experimental
      data. Moreover the values of apparent protonation constants (as adjustable
      parameters found by non-linear regression) are very near to the apparent
      constants evaluated by a Donnan model assuming the intrinsic constants in resin
      phase equal to the equilibrium constants in aqueous solution of ADA and
      considering the amphoteric nature of active sites for the evaluation of counter
      ion concentration in the resin phase. Copper removal outlined the strong affinity
      of the active groups of the resin for this ion in solution compared to the S.
      natans biomass according to the complexation constants between aminodiacetic and
      mono-carboxylic groups and copper ions.

PMID- 14637349
TI  - Kinetic models for volatile chlorinated hydrocarbons removal by zero-valent iron.
AB  - Kinetic models for removal of trichloroethylene, trichloromethane and
      tetrachloroethylene from water by zero-valent iron were tested. The
      dehalogenation reactions were modelled by first-order and power law models,
      pseudo-stationary models with a controlling surface reaction rate and non
      stationary models without the assumption of rate controlling step. Regression
      analysis proved, that the first-order kinetic is not suitable for the modelling
      of chlorinated hydrocarbons dechlorination. On the other hand, power law models,
      Langmuir-Hinshelwood analogy models and general models of heterogeneous reactions
      are reliable for the kinetic description of dechlorination. In spite of an
      empirical or semi-empirical character, the power law models and models of
      controlling surface reaction rate can be recommended for the regression analysis
      owing to the their simple regression parameters interpretation.

PMID- 14637350
TI  - Adsorption characteristics of Ni(II) on gamma-type alumina particles and its
      determination of overall adsorption rate by a differential bed reactor.
AB  - The adsorption experiment of nickel ion [Ni(II)] on gamma-type alumina by a
      differential bed reactor in aqueous solutions was investigated to determine the
      adsorption characteristics and overall adsorption rate. The adsorbed amount
      increased rapidly with pH from pH 2 to 6 and kept constant over pH 6. The
      adsorbed amount of Ni(II) increased with temperature from 20 to 50 degrees C.
      Correlation coefficients (R2) of Langmuir and Freundlich adsorption isotherms
      were 0.9268 and 0.9489, respectively, and Freundlich isotherm was more suitable
      for adsorption on gamma-type alumina than Langmuir isotherm. The overall
      adsorption rate of Ni(II) on gamma-type alumina at pH 6 by a differential bed
      rector was determined as follows: r = 68.77Ce(1.61) - 17.60qe(0.36). Al(III) ions
      in solutions were away from the alumina surface during the adsorption of Ni(II)
      and Al(III) concentration increased with an increasing Ni(II) adsorbed amount on
      alumina.

PMID- 14637351
TI  - Determining the equilibrium partitioning coefficients of volatile organic
      compounds at an air-water interface.
AB  - The single equilibration technique (SET) was adopted to determine the
      partitioning coefficients (pc) at an air-water interface for volatile organic
      compounds (VOCs), including ethanol, iso-propanol (IPA), iso-butanol (IBA),
      methyl ethyl ketone (MEK) and toluene, all extensively used in industrial
      processes. Standard SET procedures were established. The liquid concentrations
      (CL) of tested VOCs ranged from 10 to 125 mg l(-1) for alcohols and MEK, and from
      0.5 to 20 mg l(-1) for toluene. The temperatures (Tw) of aqueous VOC solutions
      were maintained at 27, 32, 38 and 42 degrees C to determine the gaseous
      concentrations at equilibrium (Cg*) and pc of VOCs, using the formula
      pc=(Cg*/CL). Results reveal that the pc values of all tested components increase
      slowly with Tw given a constant CL, and that the pc of alcohols and MEK fall as
      CL increases at a constant Tw. In contrast, the pc of toluene is not
      significantly impacted by a variation in CL at a constant Tw. However, the effect
      of CL concentration has seldom been discussed. The heats of liquid and gaseous
      phase transfer (DeltaHtr) of VOC, and the highly linear regression (with squared
      correlation coefficients, R2, from 0.901 to 0.999) between lnCg* and Tw(-1) are
      also evaluated. The experimental results and the VOC mass transfer
      characteristics are helpful for evaluating the emission of VOC from the water
      surface of wastewater treatment facilities.

PMID- 14637352
TI  - Photostabilization of the herbicide bensulfuron-methyl by using organoclays.
AB  - Photostable formulations of the herbicide bensulfuron-methyl [BSM, 2-(4,6
      dimethoxypyrimidin-2-carbamoylsulfamoyl)-o-toluic acid methyl ester] were
      achieved by adsorbing it on clays or on clays pre-adsorbed with the organic
      cation malachite green (MG). Fourier-transform infra-red (FTIR) spectra showed
      the existence of strong interactions between the pre-adsorbed MG and the
      herbicide. The photostabilization of BSM obtained with clay-MG was mainly due to
      pacification of clay surface by MG and a deactivation mechanism via energy
      transfer between the two organic molecules adsorbed on the surface of the clay.

PMID- 14637353
TI  - Cr(VI) removal from synthetic wastewater using coconut shell charcoal and
      commercial activated carbon modified with oxidizing agents and/or chitosan.
AB  - In this study, the technical feasibility of coconut shell charcoal (CSC) and
      commercial activated carbon (CAC) for Cr(VI) removal is investigated in batch
      studies using synthetic electroplating wastewater. Both granular adsorbents are
      made up of coconut shell (Cocos nucifera L.), an agricultural waste from local
      coconut industries. Surface modifications of CSC and CAC with chitosan and/or
      oxidizing agents, such as sulfuric acid and nitric acid, respectively, are also
      conducted to improve removal performance. The results of their Cr removal
      performances are statistically compared. It is evident that adsorbents chemically
      modified with an oxidizing agent demonstrate better Cr(VI) removal capabilities
      than as-received adsorbents in terms of adsorption rate. Both CSC and CAC, which
      have been oxidized with nitric acid, have higher Cr adsorption capacities (CSC:
      10.88, CAC: 15.47 mg g(-1)) than those oxidized with sulfuric acid (CSC: 4.05,
      CAC: 8.94 mg g(-1)) and non-treated CSC coated with chitosan (CSCCC: 3.65 mg g(
      1)), respectively, suggesting that surface modification of a carbon adsorbent
      with a strong oxidizing agent generates more adsorption sites on their solid
      surface for metal adsorption.

PMID- 14637354
TI  - Behavior of bromide in the photoelectrocatalytic process and bromine generation
      using nanoporous titanium dioxide thin-film electrodes.
AB  - In this study, the photoelectrocatalytic behavior of bromide and generation of
      bromine using TiO2 was investigated in the separate anode and cathode reaction
      chambers. Our results show that the generation of bromine begins around a
      flatband potential of -0.34 V vs. standard calomel electrode (SCE) at pH 3.0
      under UV illumination and increases with an increase in positive potential,
      finally reaching a steady-state concentration at 1.0 V vs. SCE. Maximum bromine
      formation occurs over the range of pH 4-6, decreasing sharply at conditions where
      the pH>7.

PMID- 14637355
TI  - Thermodynamic behaviour of sodium and calcium based sorbents in the emission
      control of waste incinerators.
AB  - The dry treatment of flue gas produced by incineration processes is discussed
      thermodynamically. The study investigates the theoretical limits achieved by
      sodium and calcium based sorbents in the removal of the pollutant species HCl,
      NOx and SO2. Calculations were performed varying the temperature and the molar
      ratio between the amount of the injected alkaline sorbent and the content of the
      pollutant gaseous species in the flue gas. Results show that sodium cation based
      sorbents are more efficient than calcium based ones in the whole investigated
      temperature range (100-600 degrees C). The higher effectiveness of sodium based
      sorbents is particularly remarkable towards hydrogen chloride, whose
      concentration can always be reduced below the values set by the environmental
      regulations. Possible improvements in the treatment efficiency of combustion
      fumes obtainable with sodium based sorbents can be mainly summarised in a lower
      concentration of HCl in the treated gas and in a partial reduction of NOx
      concentration.

PMID- 14637356
TI  - Biosorption of heavy metals using rice milling by-products. Characterisation and
      application for removal of metals from aqueous effluents.
AB  - The morphological characteristics as well as chemical composition of rice husks
      were evaluated by different techniques such as spectroscopy and thermogravimetry.
      The material, which is considered a by-product obtained from rice milling, was
      then investigated as a potential decontaminant of toxic heavy metals present in
      laboratory effluents. Studies using glass columns were carried out at room
      temperature employing 100 ml of synthetic solutions containing Cd(II) and Pb(II)
      at 100 mg l(-1) in order to study the effects of pH, flow rate and particle size
      on Cd(II) and Pb(II) adsorption. After establishing the optimised conditions, the
      potentiality of rice husks for removing Cd(II) and Pb(II) ions from 100 ml of
      laboratory effluent, presenting concentrations before treatment of 22 and 12 mg
      l(-1), respectively, was evaluated. The ability to take up other metals species,
      such as Al(III), Cu(II) and Zn(II), present in this effluent was also studied.
      According to the data obtained, under the optimised conditions (pH=4.0, flow rate
      of 8.0 ml min(-1) and < or =355 microm rice husk particle size), 30 g of husks
      were necessary to attain the permissible limits for effluent release, as
      recommend by the EPA, for those species evolved in this work (Al, Cd, Cu, Pb and
      Zn).

PMID- 14637357
TI  - Treatment of landfill leachate by ozone-based advanced oxidation processes.
AB  - In this study, laboratory experiments are conducted to compare the efficacy using
      several ozone-based advanced oxidation processes (AOPs), such as O3, O3/H2O2, and
      O3/UV, to treat landfill leachate. Raw leachate was initially coagulated by
      ferric chloride (FeCl3) at the experimental-determined optimal dosage of 900 mgl(
      1), and the ozone-based AOPs were subsequently applied. Results indicate that all
      AOPs would result in a significant increase on the ratio of BOD5/COD from 0.06 to
      0.5 at the applied ozone dosage of 1.2 gl(-1). The increase on biodegradability
      for ozonated leachate indicates that these AOPs would be beneficial to the
      subsequent biological treatment process. To better explain the alteration of high
      organic molecules after oxidation, ultrafiltration was used to separate the
      leachate by several molecular weight cutoffs (MWCO). The COD distribution for
      coagulated leachate is 34% for MWCO>10 kDa, 7% for MWCO between 5 and 10 kDa, 22%
      for MWCO between 1 and 5 kDa, and 37% for MWCO<1 kDa. Following ozonation or
      AOPs, the predominant distribution of COD would be obviously shifted to the MWCO
      less than 1000 gmol(-1) (72-85%) over the other MWCO ranges. In addition, Gel
      Permeation Chromatograph (GPC) analysis has showed a substantial agreement on the
      cleavage of larger organic compounds into smaller ones. O3/UV was found to be the
      most effective approach among these ozone-based AOPs to enhancing the
      biodegradability and eliminating the color of leachate.

PMID- 14637358
TI  - Fenton's pre-treatment of mature landfill leachate.
AB  - The aim of this study was to check the effectiveness of the Fenton's reagent
      (Fe2+ + H2O2 + H+) for the pre-treatment of a municipal landfill leachate with
      the objective of improving its overall biodegradability, evaluated in terms of
      BOD5/COD ratio, up to a value compatible with biological treatment. The leachate
      came from a municipal sanitary landfill located in southern Italy and the average
      values of its main parameters were: pH=8.2; COD=10,540 mgl(-1); BOD5=2,300 mgl(
      1); TOC=3,900 mgl(-1); NH4-N=5210 mgl(-1); conductivity=45,350 microScm(-1);
      alkalinity=21,470 mgl(-1) CaCO3. The effect of initial pH value on the pre
      treatment effectiveness was evaluated by titrating the amount of acidic by
      products formed. The extent of leachate oxidation was monitored and controlled by
      both pH and redox potential measurements. The best operational conditions for
      achieving the desired goal (i.e., BOD5/COD> or =0.5) resulted: Fe2+=275 mgl(-1);
      H2O2=3,300 mgl(-1); initial pH=3; reaction time=2 h. At the end of the Fenton's
      pre-treatment, in order to permit a subsequent biological treatment, residual
      ferric ions were removed increasing the pH up to 8.5 by adding 3 gl(-1) of
      Ca(OH)2 and 3 mgl(-1) of a cationic polyelectrolyte, the latter as an aid to
      coagulation. This final step also resulted in a further modest removal of
      residual COD due to co-precipitation phenomena.

PMID- 14637359
TI  - MTBE oxidation byproducts from the treatment of surface waters by ozonation and
      UV-ozonation.
AB  - In recent years, there has been considerable concern over the release of methyl
      tert-butyl ether (MTBE), a gasoline additive, into the aquifers used as potable
      water sources. MTBE readily dissolves in water and has entered the environment
      via gasoline spills and leaking storage tanks. In this paper, we investigate
      ozonation and UV-ozonation for treatment of MTBE in contaminated drinking water
      sources. We report the test protocol and results of using solid-phase
      microextraction (SPME) to determine the level of MTBE and its oxidation
      byproducts in samples drawn from laboratory-scale ozone and UV-ozone reactors
      being evaluated at a US EPA research facility. Analysis of a prepared MTBE
      standard indicated a detection limit on the order of 0.1 microgl(-1) with a
      repeatability of +/-0.4%. Results show that the overall rate of removal of MTBE
      via UV-ozonation in a relatively turbid surface water (15 ntu) is twice that of
      ozonation alone. In addition, GC-MS analysis of decomposition products showed
      that tert-butyl formate (TBF), methyl acetate, butene, acetone, and acetaldehyde
      were produced by both processes. TBF and butene reach similar maximum yields from
      the two processes, but are more efficiently degraded by UV-ozonation treatment.
      This indicates that these treatment processes also degrade these byproducts. In
      contrast, the remaining byproducts (methyl acetate, acetone, and acetaldehyde)
      are formed at similar levels during treatment, but are not degraded once formed.
      These byproducts may be resistant to hydrogen abstraction by hydroxyl radical.

PMID- 14637360
TI  - Removal of NOM from drinking water: Fenton's and photo-Fenton's processes.
AB  - The control of disinfection by-products during water treatment is primarily
      undertaken by reducing the levels of precursor species prior to chlorination. As
      many waters contain natural organic matter at levels of up to 15 mgl(-1) there is
      a need for a range of control methods to support conventional coagulation. Two
      such processes are the Fenton and photo-Fenton's processes and in this paper they
      are assessed for their potential to remove NOM from organic rich waters. The
      performance of both processes is shown to be depentent on pH, Fe: H2O2 ratio as
      well as Fe2+ dose. Under optimum conditions both processes achieved greater than
      90% removal of DOC and UV254 absorbance. This removal lead to the trihalomethane
      formation potential of the water being reduced from 140 to below 10 microgl(-1),
      well below UK and US standards.

PMID- 14637361
TI  - Depth-dependent blur adaptation.
AB  - Variations in blur are present in retinal images of scenes containing objects at
      multiple depth planes. Here we examine whether neural representations of image
      blur can be recalibrated as a function of depth. Participants were exposed to
      textured images whose blur changed with depth in a novel manner. For one group of
      participants, image blur increased as the images moved closer; for the other
      group, blur increased as the images moved away. A comparison of post-test versus
      pre-test performances on a blur-matching task at near and far test positions
      revealed that both groups of participants showed significant experience-dependent
      recalibration of the relationship between depth and blur. These results
      demonstrate that blur adaptation is conditioned by 3D viewing contexts.

PMID- 14637362
TI  - Temporal and spatial congruence of components of motion-onset evoked responses
      investigated by whole-head magneto-electroencephalography.
AB  - Motion-onset related components in averaged whole head co-recorded MEG and EEG
      responses of 24 adults to a low-contrast checkerboard pattern were studied. The
      aims were to identify these components, to characterize quantitatively their maps
      and to localize the underlying sources by equivalent-current-dipole (ECD)
      analyses with a spherical head model.After a weak P1, a large start-elicited
      negativity arises, comprising the novel N2a (occipital positive and parieto
      central negative, peak-latency 141 ms) and the N2 like N2b (bilateral parieto
      temporal, 175 ms) component. It is followed by a large positive stop-related
      component, P2 (156 ms after motion-offset). The corresponding MEG components N2am
      and N2bm showed bilateral dipole fields with considerable overlap. P1m has a
      single dipole field around the midline. N2a(m) and N2b(m) can be modelled with
      two bilateral ECDs with significant different locations. The study shows that
      accurate mapping and ECD analyses can distinguish two neighbouring areas of the
      visual cortex, 21+/-4 (SE) mm separated, which activities are reflected in both
      spatio-temporally closely related N2(m) components. N2a(m) and N2b(m) originate
      in the extrastriate cortex, possibly close to or in V3/V3A and MT/V5
      respectively. Motion-evoked activity in (near) V3/V3A is novel on the basis of
      EEG data.

PMID- 14637363
TI  - Topographical cone photopigment gene expression in deutan-type red-green color
      vision defects.
AB  - Eye donors were identified who had X-chromosome photopigment gene arrays like
      those of living deuteranomalous men; the arrays contained two genes encoding long
      wavelength sensitive (L) pigments as well as genes to encode middle-wavelength
      sensitive (M) photopigment. Ultrasensitive methods failed to detect the presence
      of M photopigment mRNA in the retinas of these deutan donors. This provides
      direct evidence that deuteranomaly is caused by the complete absence of M pigment
      mRNA. Additionally, for those eyes with mRNA corresponding to two different L
      type photopigments, the ratio of mRNA from the first vs. downstream L genes was
      analyzed across the retinal topography. Results show that the pattern of first
      relative to downstream L gene expression in the deuteranomalous retina is similar
      to the pattern of L vs. M gene expression found in normal retinas.

PMID- 14637364
TI  - Visual perception of extent and the geometry of visual space.
AB  - The question of how perceived extents are related to the corresponding physical
      extents is a very old question that has not been satisfactorily answered. The
      common model is that perceived extent is proportional to the product of image
      size and perceived distance. We describe an experiment that shows that perceived
      extents are substantially larger than this model predicts. We propose a model
      that accounts for our results and a large set of other results. The principal
      assumption of the model is that, in the computation of perceived extent, the
      visual angle signal undergoes a magnifying transform. Extent is often perceived
      more accurately than the common model predicts, so the computation is adaptive.
      The model implies that, although the perception of location and the perception of
      extent are related, they not related by Euclidean geometry, nor by any metric
      geometry. Nevertheless, it is possible to describe the perception of location and
      extent using a simple model.

PMID- 14637365
TI  - Texture segregation by motion under low luminance levels.
AB  - We examined the effect of average luminance level on texture segregation by
      motion. We determined the minimum presentation duration required for subjects to
      detect a target defined by motion direction against a moving background. The
      average luminance level and retinal position of the target were systematically
      varied. We found that the minimum presentation duration needed for texture
      segregation depends significantly on the average luminance level and on retinal
      position. The minimum presentation duration increased as the mean luminance
      decreased. At a very low (presumably scotopic) luminance level, the motion
      defined target was never detected rapidly. Under scotopic conditions, the minimum
      presentation duration was shorter in the periphery than in a near foveal region
      when the task was simple detection of the target. When the task included
      identifying the shape of the target patch, however, the target presented near the
      fovea was identified faster at all luminance levels. These results suggest that
      the performance of texture segregation is constrained by the spatiotemporal
      characteristics of the early visual system.

PMID- 14637366
TI  - Altered global shape discrimination in deprivation amblyopia.
AB  - To assess the effect of deprivation amblyopia on global shape discrimination,
      sensitivity to radial deformation of circular patterns was assessed in patients
      treated for congenital (N=7) or developmental (N=1) cataracts. Elevation in
      radial deformation threshold was dependent on circular contour frequency and the
      depth of amblyopia. Analysis of thresholds expressed as Weber fractions indicated
      a shift in global integration to a larger scale. In a pedestal experiment,
      equivalent intrinsic noise increased in proportion to the depth of amblyopia. The
      results suggest neural undersampling in V1 and/or higher visual cortical areas in
      deprivation amblyopia and a possible role for neural disarray.

PMID- 14637367
TI  - Long range interactions between object-motion and self-motion in the perception
      of movement in depth.
AB  - Self-motion through a three-dimensional array of objects creates a radial flow
      pattern on the retina. We superimposed a simulated object moving in depth on such
      a flow pattern to investigate the effect of the flow pattern on judgments of both
      the time to collision (TTC) with an approaching object and the trajectory of that
      object. Our procedure allowed us to decouple the direction and speed of simulated
      self motion-in-depth (MID) from the direction and speed of simulated object MID.
      In Experiment 1 we found that objects with the same closing speed were perceived
      to have a higher closing speed when self-motion and object-motion were in the
      same direction and a lower closing speed when they were in the opposite
      direction. This effect saturated rapidly as the ratio between the speeds of self
      motion and object-motion was increased. In Experiment 2 we found that the
      perceived direction of object-MID was shifted towards the focus of expansion of
      the flow pattern. In Experiments 3 and 4 we found that the erroneous biases in
      perceived speed and direction produced by simulated self-motion were
      significantly reduced when binocular information about MID was added. These
      findings suggest that the large body of research that has studied motion
      perception using stationary observers has limited applicability to situations in
      which both the observer and the object are moving.

PMID- 14637368
TI  - The role of short-wavelength sensitive cones and chromatic aberration in the
      response to stationary and step accommodation stimuli.
AB  - The aim of the experiment was to test for a contribution from short-wavelength
      sensitive cones to the static and step accommodation response, to compare
      responses from short and long- plus middle-wavelength sensitive cone types, and
      to examine the contribution of a signal from longitudinal chromatic aberration to
      the accommodation response. Accommodation was monitored continuously (eight
      subjects) to a square-wave grating (2.2 c/d; 0.57 contrast) in a Badal optometer.
      The grating stepped (1.00 D) randomly towards or away from the eye from a
      starting position of 2.00 D. Five illumination conditions were used to isolate
      cone responses, and combine them with or without longitudinal chromatic
      aberration. Accuracy of the response before the step, step amplitude, latencies
      and time-constants, were compared between conditions using single factor ANOVA
      and t-test comparisons. Both S-cones and LM-cones mediated static and step
      accommodation responses. S-cone contrast drives "static" accommodation for near,
      but the S-cone response is too slow to influence step dynamics when LM-cones
      participate.

PMID- 14637369
TI  - Time-varying, slow-phase component interaction in congenital nystagmus.
AB  - We investigated the nystagmus of a 12-year-old boy with suspected X-linked
      congenital nystagmus (CN) and exophoria to determine the underlying mechanisms
      and component signals in the 'dual-velocity' and other slow phases of his
      Asymmetric (a)Periodic Alternating Nystagmus (APAN). Fast Fourier transforms
      (FFT) were performed on the waveforms and residual data after subtracting a
      sawtooth waveform whose amplitude and frequency matched those of the jerk
      nystagmus. The FFT analyses identified two frequency components (jerk--4 Hz and
      pendular--4 and 8 Hz, variable) that varied differently in intensity and
      frequency/phase over the time-course of the APAN. We synthesized each of the
      patient's slow phases using summation of sawtooth and sinusoidal waveforms. The
      resulting waveforms included jerk (with different slow-phase appearances), dual
      jerk, and pendular. We demonstrated that the pendular nystagmus seen during the
      neutral phase of APAN and the appearance of either decelerating (mimicking latent
      nystagmus), dual-velocity, or dual-jerk slow phases can be explained and produced
      by the summation of linear and pendular components of variable amplitudes and
      frequencies/phases. Thus, one mechanism may be responsible for all the variation
      seen in this patient's slow phases, rather than the less parsimonious hypothesis
      of a switched-tonic-imbalance mechanism that we had originally suggested to
      simulate the dual-velocity waveform.

PMID- 14637370
TI  - Is the perception of brightness different in poor readers?
AB  - The transient system deficit hypothesis (TSDH) of specific reading disability
      [Percept. Psychophys. 40 (1986) 440] remains contentious. As part of a study
      examining multiple measures of transient and sustained system function,
      heterochromatic flicker matching (HFM) and brightness matching (HBM) were
      assessed in 30 poor readers (9.11+/-0.68 years) and 30 age, grade and sex matched
      controls (9.24+/-0.73 years). HBM and HFM are known to reflect the processing of
      brightness and luminance information and have been related to the function of
      magnocellular and parvocellular visual sub-systems. Flicker and brightness
      matches were determined for blue, green, yellow and red stimuli on Macintosh
      colour displays using 2AFC and double interleaved random staircases. A ratio of
      the luminances for brightness and flicker matches represented performance. A
      significant difference between controls and poor readers in performance for red
      and blue stimuli was found indicating different visual function in poor readers.
      While not providing direct support for the transient system deficit hypothesis,
      this effect implies a mismatch between those achromatic systems that subserve HFM
      and those more complex mechanisms involved in HBM. The most important aspect of
      this finding is that poor readers and normal controls could be differentiated on
      the basis of a paradigm known to be contingent upon magnocellular and
      parvocellular functioning.

PMID- 14637371
TI  - Application of proteomics to the study of molecular mechanisms in
      neurotoxicology.
AB  - The proteome is the protein compliment of the genome and is the result of genetic
      expression, ribosomal synthesis and proteolytic degradation. Proteins participate
      in most major cell processes and their function is highly regulated by post
      translational modifications such as phosphorylation and glycosylation. As a
      result, neurotoxicant-induced changes in protein levels, function or regulation
      could have a negative impact on neuronal viability. At the molecular level,
      direct oxidative or covalent modifications of individual proteins by various
      chemicals or drugs is likely to lead to perturbation of tertiary structure and a
      loss of function. The proteome and the functional determinants of its individual
      protein components are, therefore, likely targets of neurotoxicant action and
      resulting characteristic disruptions could be critically involved in
      corresponding mechanisms of neurotoxicity. Clearly, investigating changes in the
      proteome can provide important clues for deciphering mechanisms of toxicant
      action and, therefore, proteomics, the study of the proteome, is currently, and
      will likely remain, a significant experimental approach for mechanistic research
      in neurotoxicology. The purpose of this review is to discuss proteomics as a tool
      for neurotoxicological investigations. A variety of classic proteomic techniques
      (e.g. liquid chromatography (LC)/tandem mass spectroscopy, two-dimensional gel
      image analysis) as well as more recently developed approaches (e.g. two-hybrid
      systems, antibody arrays, protein chips, isotope-coded affinity tags, ICAT) are
      available to determine protein levels, identify components of multiprotein
      complexes and to detect post-translational changes. Proteomics, therefore, offers
      a comprehensive overview of cell proteins, and in the case of neurotoxicant
      exposure, can provide quantitative data regarding changes in corresponding
      expression levels and/or post-translational modifications that might be
      associated with neuron injury.

PMID- 14637372
TI  - Manganese distribution in brains of Sprague-Dawley rats after 60 days of
      stainless steel welding-fume exposure.
AB  - Welders working in a confined space, as in the shipbuilding industry, are at risk
      of being exposed to high concentrations of welding fumes and developing
      pneumoconiosis or other welding-fume exposure related diseases. Among such
      diseases, manganism resulting from welding-fume exposure remains a controversial
      issue, as the movement of manganese into specific brain regions has not yet been
      clearly established. Accordingly, to investigate the distribution of manganese in
      the brain after welding-fume exposure, male Sprague-Dawley rats were exposed to
      welding fumes generated from manual metal arc-stainless steel (MMA-SS) at
      concentrations of 63.6 +/- 4.1 mg/m(3) (low dose, containing 1.6 mg/m(3) Mn) and
      107.1 +/- 6.3 mg/m(3) (high dose, containing 3.5 mg/m(3) Mn) total suspended
      particulate (TSP) for 2 h per day in an inhalation chamber over a 60-day period.
      Blood, brain, lung, and liver samples were collected after 2 h, 15, 30, and 60
      days of exposure and the tissues analyzed for their manganese concentrations
      using an atomic absorption spectrophotometer. Although dose- and time-dependent
      increases in the manganese concentrations were found in the lungs and livers of
      the rats exposed for 60 days, only slight manganese increases were observed in
      the blood during this period. Major statistically significant increases in the
      brain manganese concentrations were detected in the cerebellum after 15 days of
      exposure and up until 60 days. Slight increases in the manganese concentrations
      were also found in the substantia nigra, basal ganglia (caudate nucleus, putamen,
      and globus pallidus), temporal cortex, and frontal cortex, thereby indicating
      that the pharmacokinetics and distribution of the manganese inhaled from the
      welding fumes were different from those resulting from manganese-only exposure.

PMID- 14637373
TI  - Morphological effects of neuropathy-inducing organophosphorus compounds in
      primary dorsal root ganglia cell cultures.
AB  - Chick embryo dorsal root ganglia (DRG) cultures were used to explore early
      pathological events associated with exposure to neuropathy-inducing
      organophosphorus (OP) compounds. This approach used an in vitro neuronal system
      from the species that provides the animal model for OP-induced delayed neuropathy
      (OPIDN). DRG were obtained from 9-day-old chick embryos, and grown for 14 days in
      minimal essential medium (MEM) supplemented with bovine and human placental sera
      and growth factors. Cultures were then exposed to 1 microM of the OP compounds
      phenyl saligenin phosphate (PSP) or mipafox, which readily elicit OPIDN in hens,
      paraoxon, which does not cause OPIDN, or the DMSO vehicle. The medium containing
      these toxicants was removed after 12 h, and cultures maintained for 4-7 days post
      exposure. Morphometric analysis of neurites was performed by inverted microscopy,
      which demonstrated that neurites of cells treated with mipafox or PSP but not
      with paraoxon had decreased length-to-diameter ratios at day 4 post-exposure.
      Ultrastructural alterations of neurons treated with PSP and mipafox included
      dissolution of microtubules and neurofilaments and degrading mitochondria.
      Paraoxon-treated and DMSO control neuronal cell cultures did not show such
      evident ultrastructural changes. This study demonstrates that chick DRG show
      pathological changes following exposure to neuropathy-inducing OP compounds.

PMID- 14637374
TI  - A new animal model of vincristine-induced nociceptive peripheral neuropathy.
AB  - Using doses close to those used clinically, we have developed an animal model of
      vincristine-induced nociceptive sensory neuropathy after repeated intravenous
      injection in male Sprague-Dawley rats. In order to validate the model, three
      different doses (50, 100 and 150 microg/kg) of vincristine were injected every
      2nd day until five injections had been given. The sensory behavioural assessment
      revealed mechanical hyperalgesia and allodynia associated with cold thermal
      hyperalgesia and allodynia. With regard to electrophysiological evaluation, we
      observed a decrease in the nerve conduction velocity in the highest dose group.
      Morphological studies revealed few degenerated fibers in the sciatic nerve and
      many degenerated myelinated axons in the fine nerve fibers of the subcutaneous
      paw tissue. Finally, to develop an animal model, we chose the 150 microg/kg dose
      because of the good general clinical status of the rats without motor function
      changes associated with severe sensation disorders like hyperalgesia and
      allodynia. This model of vincristine-induced painful neuropathy will be used to
      explore physiopathological mechanisms implied in the genesis of neuropathic pain
      and also to test new analgesic and neuroprotective drugs.

PMID- 14637375
TI  - Fipronil modulation of glutamate-induced chloride currents in cockroach thoracic
      ganglion neurons.
AB  - Fipronil is the first phenylpyrazole insecticide introduced for pest control. It
      is effective against some insects that have become resistant to other
      insecticides, and exhibits low mammalian toxicity. Although fipronil is known to
      block GABA receptors, the mechanisms of its selective toxicity and efficacy
      against insects with dieldrin-resistant GABA receptors are not fully understood.
      We studied the effects of fipronil on the inhibitory glutamate receptor-chloride
      channel complex, which is found only in invertebrates. Glutamate-activated
      chloride currents were recorded from neurons isolated from cockroach thoracic
      ganglia using the whole-cell patch clamp technique. When glutamate was applied to
      a neuron, it evoked inward currents with an EC50 of 36.8 +/- 3.0 microM and a
      Hill coefficient of 1.56 +/- 0.17. The similarity between the reversal potential
      and the calculated chloride equilibrium potential indicated that glutamate
      induced currents were carried by chloride ions. Fipronil suppressed the glutamate
      induced peak currents in a dose-dependent manner with an IC50 of 0.73 +/- 0.27
      microM and a Hill coefficient of 0.68 +/- 0.15. The current decay phases were
      greatly prolonged after fipronil application in a concentration-dependent manner.
      Picrotoxinin (PTX) at 100 microM slightly suppressed glutamate-induced currents
      to 87.8 +/- 3.7% of the control, and dieldrin at 100 microM had no effect (96.7
      +/- 3.1%). AP5 and CNQX, mammalian glutamate receptor antagonists, were without
      effect on glutamate-induced Cl- currents. It is concluded that the potent
      blocking action of fipronil against glutamate-gated chloride channels may
      contribute to the higher toxicity against insects than mammals, as well as the
      efficacy against insects resistant to other insecticides.

PMID- 14637376
TI  - [3H]Ethynylbicycloorthobenzoate ([3H]EBOB) binding in recombinant GABAA
      receptors.
AB  - Ethynylbicycloorthobenzoate (EBOB) is a recently developed ligand that binds to
      the convulsant site of the GABAA receptor. While a few studies have examined the
      binding of [3H]EBOB in vertebrate brain tissue and insect preparations, none have
      examined [3H]EBOB binding in preparations that express known configurations of
      the GABAA receptor. We have thus examined [3H]EBOB binding in HEK293 cells stably
      expressing human alpha1beta2gamma2 and alpha2beta2gamma2 GABAA receptors, and the
      effects of CNS convulsants on its binding. The ability of the CNS convulsants to
      displace the prototypical convulsant site ligand, [35S]TBPS, was also assessed.
      Saturation analysis revealed [3H]EBOB binding at a single site, with a K(d) of
      approximately 9 nM in alpha1beta2gamma2 and alpha2beta2gamma2 receptors. Binding
      of both [3H]EBOB and [35S]TBPS was inhibited by dieldrin, lindane, tert
      butylbicycloorthobenzoate (TBOB), PTX, TBPS, and pentylenetetrazol (PTZ) at one
      site in a concentration-dependent fashion. Affinities were in the high nM to low
      microM range for all compounds except PTZ (low mM range), and the rank order of
      potency for these convulsants to displace [3H]EBOB and [35S]TBPS was the same.
      Low [GABA] stimulated [3H]EBOB binding, while higher [GABA] (greater than 10
      microM) inhibited [3H]EBOB binding. Overall, our data demonstrate that [3H]EBOB
      binds to a single, high affinity site in alpha1beta2gamma2 and alpha2beta2gamma2
      GABAA receptors, and modulation of its binding is similar to that seen with
      [35S]TBPS. [3H]EBOB has a number of desirable traits that may make it preferable
      to [35S]TBPS for analysis of the convulsant site of the GABAA receptor.

PMID- 14637377
TI  - Formate, the toxic metabolite of methanol, in cultured ocular cells.
AB  - Methanol has neurotoxic actions on the human retina due to its metabolite, formic
      acid, which is a mitochondrial toxin. In methanol poisoned animals, morphologic
      changes were seen both in retinal photoreceptors and in cells of the underlying
      retinal pigment epithelium (RPE). Here the effects of formate exposure on the two
      retinal cell types were analyzed in more detail in vitro using photoreceptor
      (661W) and RPE (ARPE-19) cell lines. Cells were exposed for time courses from
      minutes to days to sodium formate at pH 7.4 or to formic acid at pH 6.8, to
      simulate the metabolic acidosis that accompanies methanol poisoning. Formate
      accumulation, cellular ATP, cytotoxicity (lactate dehydrogenase (LDH) release)
      and cell phenotype were analyzed. Formate accumulated with a similar biphasic
      pattern in both cell types, and to similar levels whether delivered as sodium
      formate or as formic acid. ATP changes with sodium formate treatment differed
      between cell types with only 661W cells showing a rapid (within minutes),
      transient ATP increase. The subsequent ATP decrease was earlier in 661W cells (6
      h) than the ATP decrease in ARPE-19 cells (24 h), and although both cell types
      showed evidence of cytotoxicity, the effects were greater for 661W cells. Both
      cell types showed enhanced morphologic and biochemical changes with formic acid
      treatment including earlier and/or greater effects on ATP depletion and
      cytotoxicity; again effects were more pronounced in 661W cells. Formate therefore
      is toxic for both cell lines, with 661W cells exhibiting greater sensitivity.
      Medium pH also appears to play a significant role in formate toxicity in vitro.

PMID- 14637378
TI  - Calcification mimicking manganese-induced increased signal intensities in T1
      weighted MR images in a patient taking herbal medicine: case report.
AB  - Characteristic high signal intensities confined to the globus pallidus on T1
      weighted magnetic resonance image (MRI) can be observed in manganese (Mn)-exposed
      workers, however, these high signals should be differentiated from those due to
      other causes such as fat, hemoglobin breakdown products, melanoma,
      neurofibromatosis, and calcification. A 39-year-old woman was admitted with
      mutism and involuntary movements which had developed the day before. She had
      ingested two packs of liquid herbal medicine containing 0.53 mg of Mn daily for 4
      months prior to visiting our hospital. Her MRI showed high signals, confined
      mainly to the globus pallidus on T1-weighted images. Follow-up brain MRI at an
      interval of 11 months showed no interval change. Brain computed tomography (CT)
      at the time of the second MRI showed symmetric calcification on both globus
      pallidus. Blood levels of liver function tests, calcium, phosphorus, and
      parathyroid hormone were within normal ranges. The increased signals, which were
      first presumed to be induced by Mn, were concluded to be due to calcification
      based on the following reasons. First, follow-up brain MRI at an interval of 11
      months did not show any interval change. Second, the ingested amount of 1.06 mg
      Mn daily for 4 months is even less than that added to mineral supplements for
      adults. Third, Mn-induced high signals in T1-weighted MRI do not show any
      abnormal findings in brain CT. The present case report suggests that brain CT
      should be performed to rule out symmetric calcification on basal ganglia in
      patients showing increased signals in T1-weighted MRI, but who do not have a
      significant exposure history to Mn. The present report also showed that the
      amount of 1.06 mg Mn daily ingested for 4 months did not cause the high signal in
      brain MRI.

PMID- 14637379
TI  - Interactions of paraquat and triadimefon: behavioral and neurochemical effects.
AB  - Triadimefon (TDF), a triazole fungicide, and paraquat (PQ), a non-selective
      herbicide/dessicant, are both known to adversely impact brain dopaminergic
      function and are used in overlapping geographical areas of the US. Since "real
      world" situations indicate humans are exposed to a diverse mixture of chemicals,
      this study hypothesized that combined exposures to PQ+TDF could produce
      interactive effects by simultaneously attacking multiple target sites of dopamine
      systems. Thus, 10 mg/kg PQ (PQ10) and 25 or 50 mg/kg TDF (TDF25 and 50,
      respectively) were administered i.p. to male C57BL/6 mice, 2x per week for 12
      weeks, either alone or in combination. Acutely, TDF50 increased horizontal and
      vertical activity with increased vertical activity still occurring 24h later,
      indicative of sustained behavioral sensitization. Acutely, PQ decreased
      horizontal but not vertical activity with a lack of residual effects at 24h. PQ
      prevented the increased levels of activity associated with TDF50. These
      interactions differed for horizontal and vertical activity, indicating their
      differential neurochemical mediation, and suggesting that they did not arise from
      simple additivity of PQ and TDF effects. Nor could the interactive effects be
      readily ascribed to corresponding neurochemical interactions, since all
      treatments generally increased levels of DA and metabolites acutely in striatum
      and were associated with general reductions in levels of DA and metabolites and
      turnover in striatum and frontal cortex 7 days after the final treatment. Thus,
      TDF and PQ both separately and through interactions may serve as environmental
      risk factors through different mechanisms for dopaminergically-mediated
      behavioral dysfunctions.

PMID- 14637380
TI  - Perinatal exposure to polychlorinated biphenyls alters excitatory synaptic
      transmission and short-term plasticity in the hippocampus of the adult rat.
AB  - Developmental exposure to polychlorinated biphenyls (PCBs) has been associated
      with cognitive deficits in humans and laboratory animals. Previous work has
      demonstrated a reduced capacity to support long-term potentiation (LTP) in
      animals exposed to a PCB mixture, Aroclor 1254 (A1254) via the dam in utero and
      throughout the preweaning period [Brain Res. 850;1999:87-95; Toxicol. Sci.
      57;2000:102-11]. Assessment of normalized input/output (I/O) functions collected
      prior to LTP induction failed to reveal consistent differences in baseline
      synaptic transmission between control and PCB-exposed groups. The present study
      was designed to systematically evaluate excitatory and inhibitory synaptic
      transmission using a more extensive I/O analysis and paired pulse functions to
      assess short-term plasticity. Pregnant Long-Evans rats were administered either
      corn oil (control) or 6 mg/kg per day of A1254 by gavage from gestational day
      (GD) 6 until pups were weaned on postnatal day (PND) 21. In adult male offspring
      (5-11 months of age), field potentials evoked by perforant path stimulation were
      recorded in the dentate gyrus under urethane anesthesia. Detailed I/O functions
      were assessed by averaging the responses evoked in the dentate gyrus to stimulus
      pulses delivered to the perforant path in an extensive ascending intensity
      series. Population spike (PS) and postsynaptic potential (PSP) amplitudes
      recorded in the dentate gyrus were significantly enhanced in PCB-exposed animals
      relative to controls at midrange intensities. No group differences were observed
      in EPSP slope amplitudes. Short-term plasticity was assessed by delivering pairs
      of stimulus pulses at interpulse intervals (IPIs) ranging from 10 to 70 ms. In
      the dentate gyrus this range of intervals activates both inhibitory and
      excitatory mechanisms leading to a pattern of depression at brief intervals (<30
      ms) followed by facilitation as the interval between pulses is extended. Paired
      pulse depression was decreased at an intermediate IPI (30 ms) with submaximal
      stimulus intensities. These data augment previous work demonstrating persistent
      changes in hippocampal plasticity as a result of exposure to PCBs during
      development. Furthermore, as increases in field potential amplitudes were
      observed, these findings support previous conclusions that A1254-induced LTP
      deficits are not readily attributable to reductions in synaptic excitability.
      Thus, in addition to impairment in use-dependent synaptic plasticity reported
      previously, the present report reveals that basic components of information
      processing within the hippocampus are permanently altered as a result of
      perinatal exposure to PCBs.

PMID- 14637381
TI  - Subchronic inhalation neurotoxicity studies of ethyl acetate in rats.
AB  - Rats were exposed to 0, 350, 750 or 1500 ppm of ethyl acetate by inhalation for 6
      h per day, 5 days per week for 13 weeks. Functional observational battery (FOB)
      and motor activity tests occurred on non-exposure days during weeks 4, 8 and 13,
      after which tissues were microscopically examined for neuropathology. A subset of
      rats was monitored during a 4-week recovery period. Exposure to 750 and 1500 ppm,
      diminished behavioral responses to unexpected auditory stimuli during the
      exposure session and appeared to be an acute sedative effect. There were no signs
      of acute intoxication 30 min after exposure sessions ended. Rats exposed to 750
      and 1500 ppm had reduced body weight, body weight gain, feed consumption, and
      feed efficiency, which fully or partially recovered within 4 weeks. Reductions in
      body weight gain and feed efficiency were observed in male rats exposed to 350
      ppm. The principal behavioral effect of subchronic exposure was reduced motor
      activity in the 1500 ppm females, an effect that was not present after the 4-week
      recovery period. All other FOB and motor activity parameters were unaffected, and
      no pathology was observed in nervous system tissues. Operant sessions were
      conducted in another set of male rats preconditioned to a stable operant baseline
      under a multiple fixed ratio-fixed interval (FR-FI) schedule of food
      reinforcement. FR response rate, FR post-reinforcement pause duration, and the
      pattern of FI responding were not affected during or after the exposure series.
      In contrast, within-group FI rate for the treatment groups increased over time
      whereas those of the controls decreased. A historical control group, however,
      also showed a similar pattern of increase, indicating that these changes did not
      clearly represent a treatment-related effect. Results from these studies indicate
      a LOEL of 350 ppm for systemic toxicity based on the decreased body weight gain
      in male rats, and a LOEL of 1500 ppm for neurotoxicity based on the transient
      reduction in motor activity in female rats. In conclusion, there was no evidence
      that subchronic exposure up to 1500 ppm ethyl acetate produced any enduring
      neurotoxic effects in rats.

PMID- 14637382
TI  - The utility of biological monitoring for manganese in ferroalloy smelter workers
      in South Africa.
AB  - Five hundred and nine workers at a manganese (Mn) smelting works comprising eight
      production facilities and 67 external controls were studied cross-sectionally.
      Exposure measures from personal sampling included inhalable dust, cumulative
      exposure indices (CEI) and average intensity (INT = CEI/years exposed) calculated
      for the current job at the smelter and also across all jobs held by subjects.
      Biological exposure was measured by Mn in the blood (MnB) and urine (MnU) and
      biological effect was measured by serum prolactin. Average lifetime exposure
      intensity across all jobs ranged from near 0 (0.06 microg/m3) for unexposed
      external referents to 5 mg/m3. Atmospheric exposures and MnB and MnU
      distributions were consistent with published data for both unexposed and smelter
      workers. Associations between biological exposures and groups defined by
      atmospheric exposures in the current job were substantial for MnB, less so for
      MnU and absent for serum prolactin. Random sampling of MnB measurements
      representative of a group of workers with more than 1-2 years of service in the
      same job and notionally homogenous exposure conditions could serve as a cross
      sectional predictor of atmospheric Mn exposure in the current job, as well as for
      surveillance of Mn exposure trends over time. Correlations at the individual
      level were only modest for MnB (33% of the variance in log atmospheric Mn
      intensity in the current job was explained by log MnB), much worse for MnU (only
      7%). However, a receiver operating characteristic (ROC) analysis was performed
      which showed that it is possible to use a MnB cut-off of 10 microg/l (the 95th
      percentile in the unexposed) to good effect as a screening tool to discriminate
      between individual exposures exceeding and falling below a relatively strict
      atmospheric Mn exposure threshold at the ACGIH threshold limit value (TLV) of 0.2
      mg/m3. MnU has no utility as a measure of biological exposure nor does serum
      prolactin as a measure of biological effect.

PMID- 14637383
TI  - The nervous system effects of occupational exposure on workers in a South African
      manganese smelter.
AB  - Five hundred and nine production workers at a manganese (Mn) smelting works
      comprising eight production facilities and 67 external controls were studied
      cross-sectionally for Mn related neuroehavioural effects. Exposure measures from
      personal sampling included Mn in inhalable dust as cumulative exposure indices
      (CEI) and average intensity (INT). Biological exposure and biological effect
      measures included blood (MnB), urine (MnU) manganese and serum prolactin.
      Endpoints included items from the Swedish nervous system questionnaire (Q16),
      World Health Organisation neurobehavioural core test battery (WHO NCTB), Swedish
      performance evaluation system (SPES), Luria-Nebraska (LN), and Danish product
      development (DPD) test batteries, and a brief clinical examination. Potential
      confounders and effect modifiers included age, educational level, alcohol and
      tobacco consumption, neurotoxic exposures in previous work, past medical history,
      previous head injury and home language. Associations were evaluated by multiple
      linear and logistic regression modelling. Modelling assumptions were tested.
      Average exposure intensity across all jobs ranged from near 0 (0.06 microg/m3)
      for external controls to 5.08 mg/m3 for inhalable Mn, and was greater than the
      ACGIH TLV for 69% of subjects. Results from the large number of tests performed
      resolved into three groups. Group 1 shows differences between external unexposed
      referents and all the exposed and/or differences between internal low exposed
      referents and the rest of the exposed but no further exposure-response
      relationships. It includes the Santa Ana, Benton and digit-span tests from the
      WHO NCTB; the hand tapping and endurance tapping tests from the SPES; Luria
      Nebraska item 2L; questionnaire items tired, depressed, irritated, having to take
      notes in order to remember things, and subjects' perception that they had sex
      less often than normal; a test of clinical abnormality; and increased sway under
      two conditions (eyes open without foot insulation, eyes open with foot
      insulation). Group 2 shows the presence of a more substantive exposure-response
      relationship. It consists of only two tests: and includes the WHO digit-symbol
      test (although the major impact is at low exposure and therefore
      counterintuitive, arguably placing this test in group 3) and the LN item 1R which
      has a step to a poorer score at high exposure. Group 3 contains the overwhelming
      majority of test results (almost all the questionnaire items, almost all the DPD
      tests including tremor, sway and diadochokinesia, and serum prolactin) which were
      either null or counterintuitive (did not make sense). The CEI was the strongest
      predictor of test abnormalities, except for the clinical test which was more
      strongly associated with blood manganese. Despite a comprehensive range of
      endpoints, and levels of exposure ranging from environmental to industrial, this
      large study of Mn workers found little convincing evidence for a continuum of
      effects, contributing further questions to current debates about the adequacy of
      the current ACGIH TLV.

PMID- 14637384
TI  - Resiniferatoxin-induced loss of plasma membrane in vanilloid receptor expressing
      cells.
AB  - Resiniferatoxin (RTX), a potent analog of capsaicin, was evaluated
      electrophysiologically in dorsal root ganglion (DRG) cells and cell lines
      ectopically expressing the vanilloid receptor type 1 (VR1) to determine if cell
      phenotype influenced RTXs neurotoxic properties. Furthermore, capsaicin and heat
      activation of VR1 were evaluated in these cells to determine if cellular damage
      was unique to RTX activation of the receptors. RTX application to DRG cells
      identified as type 1, 2 or 5, cell types known to express VR1, induced large
      inward currents. RTX did not induce currents in DRG cells that do not express the
      receptor (type 4 cells). In cell lines ectopically expressing VR1, RTX-induced
      similar currents. RTX produced no effect in non-transfected cells. After exposure
      to RTX both DRG cells and transfected cells failed to respond to subsequent
      applications of the agonist. In addition, whole cell capacitance was reduced up
      to 70%. The decrease in capacitance was associated with the loss of plasma
      membrane, as determined by confocal microscopy. Cell phenotype, other than VR1
      expression, did not influence the response to RTX. Interestingly, capsaicin and
      heat activation of vanilloid receptors also decreased cell capacitance, but the
      loss of membrane was not as great as with RTX and responses to these stimuli were
      not lost after the initial exposure. The loss of cell membrane required elevated
      intracellular levels of Ca2+. From these data it was concluded that the loss of
      cell membrane was dependent on the presence of both VR1 and intracellular Ca2+
      accumulation, but not on cell phenotype.

PMID- 14637386
TI  - Advanced breast cancer: an update and controversies on diagnosis and therapy.
AB  - This review on advanced breast cancer considered important differences in the
      actual definition of this condition. Advanced breast cancer includes locally
      advanced, locoregionally recurrent and metastatic disease, which have different
      diagnosis, prognosis and therapy; their actual definitions are relatively
      uncertain. Differently from the common opinion that metastatic breast cancer
      (MBC) is a very severe incurable disease, recently it has been reported that a
      small but not irrelevant fraction of MBC patients can be cured or remain in long
      term survival with complete remission. The type of metastases of the population
      studied in these reports was analysed and the authors hypothesised that the
      particularly high DFS reported mainly was attributable to the high proportion of
      patients with locoregional metastases only. Furthermore, the options and
      associations of the drug therapy available for treatment of advanced breast
      cancer have been reviewed.

PMID- 14637385
TI  - Whole blood manganese correlates with high signal intensities on T1-weighted MRI
      in patients with liver cirrhosis.
AB  - We examined whole blood (MnB), plasma (MnP) and urinary Mn (MnU) concentrations
      in 33 cirrhotics and 11 healthy controls to clarify: (1) whether, in chronic
      liver diseases, MnB or MnP reflects pallidal signal intensities in magnetic
      resonance imaging (MRI); and (2) which factors in chronic liver diseases
      correlate with pallidal signal intensities in T1-weighted MRI. Increased signal
      intensity in the pallidum was observed in 27 (81.8%) of 33 patients with liver
      cirrhosis in T1-weighted MRI. There was a significant correlation between MnB and
      pallidal index (PI) (gamma = 0.559, P < 0.01) in the patients. However, no
      significant correlation was observed between MnP and PI (gamma = 0.353, P >
      0.05). According to a multiple linear regression, MnB reflected the signal
      intensities of T1-weighted MRI better than MnP or MnU. Child/Pugh score and total
      bilirubin level also correlated with PI. However, the hemoglobin level did not
      correlate with PI significantly.

PMID- 14637387
TI  - Estrogen/EGF receptor interactions in breast cancer: rationale for new
      therapeutic combination strategies.
AB  - In the therapy of estrogen receptor (ER) positive human mammary carcinomas, the
      treatment with the antiestrogen tamoxifen has been well established. However, the
      development of hormone resistance is an important factor in breast cancer
      progression against endocrine therapy. The presence of the receptor for EGF
      (EGFR) correlates with lack of response towards antiestrogen therapy. The EGFR is
      not only involved in tumor cell growth, survival signaling, cell migration,
      metastasis formation and angiogenesis, but also seems to confer reduced responses
      of tumor cells towards anti-hormones. Concomitant inhibition of both, the
      receptors for estrogen and EGF may be necessary to improve breast cancer therapy.

PMID- 14637388
TI  - "Tumour marker guided" salvage treatment prolongs survival of breast cancer
      patients: final report of a 7-year study.
AB  - OBJECTIVES: Randomised trials on breast cancer showed no significant benefit from
      post-operative follow-up with clinical and/or conventional radiological means. We
      hypothesised that carcinoembryonic antigen (CEA), tissue polipeptyde antigen
      (TPA), breast cancer associated antigen 115 D8/DF3 (CA15.3) tumour marker panel
      is sensitive enough for significantly anticipating salvage treatment and
      prolonging survival of relapsing breast cancer patients. METHODS: From October
      1981 to May 1999, 68 (62%) of 109 patients with distant metastases were
      recruited. Thirty-six (53%) received salvage treatment at the time of significant
      increase in one or more components of CEA-TPA-CA15.3 tumour marker panel and
      negative instrumental examinations ("tumour marker guided" treatment) and 32
      (47%) were treated only after radiological confirmation of metastases
      (conventional treatment). The prognostic factors of the two groups did not show
      any statistically significant difference. RESULTS: The time from one or more
      tumour marker increase to clear clinical and/or radiological signs of distant
      metastases (lead time) was significantly prolonged in the 36 patients with
      "tumour marker guided" treatment (17.3 +/- 13.1 vs. 2.9 +/- 2.9 months, P <
      0.001, Wilcoxon test) as well as the survival curves from salvage therapy and
      from mastectomy (the proportion of survivors was: at 36 months from salvage
      therapy 28% vs. 9%, P = 0.0094; at 84 months from mastectomy 42% vs. 19%, P =
      0.0017). The multivariate Cox analysis showed that time from mastectomy to tumour
      marker increase and "tumour marker guided" salvage treatment were the only
      significantly different variables (P = 0.00001 and 0.005, respectively).
      CONCLUSION: These data point out that "tumour marker guided" salvage treatment
      significantly prolongs disease-free and overall survivals of relapsing responsive
      patients.

PMID- 14637389
TI  - Intracrine mechanism of estrogen synthesis in breast cancer.
AB  - It has been demonstrated that biologically active estrogens are locally produced
      from circulating inactive steroids in an intracrine mechanism in the breast
      carcinoma. The in situ production of estrogens is considered to play an important
      role in the proliferation of breast cancer cells, especially in the
      postmenopausal women. Therefore, the total blockade of this pathway may lead to
      an improvement in the prognosis in breast cancer patients due to the inhibition
      of estrogenic actions. In this review, we describe the recent studies of enzymes
      related to intracrine mechanism of estrogen synthesis, including aromatase,
      steroid sulfatase (STS), and 17beta-hydroxysteroid dehydrogenase, in human breast
      carcinoma tissues, and discuss the biological significance of local production of
      estrogens in human breast cancer.

PMID- 14637390
TI  - Anti-angiogenic therapy in breast cancer.
AB  - Breast cancer is a worldwide epidemic among women, and one of the most rapidly
      increasing cancers. Not only the incidence rate but also the death rate is
      increasing. Despite enthusiastic efforts in early diagnosis, aggressive surgical
      treatment and application of additional non-operative modalities, its prognosis
      is still dismal. This emphasizes the necessity to develop new measures and
      strategies for its prevention. The understanding of the biology of angiogenesis
      is improving rapidly, offering the hope for more specific vascular targeting of
      tumor neovasculature. Anti-angiogenic therapy is a promising, relatively new form
      of cancer treatment using drugs called angiogenesis inhibitors that specifically
      inhibit new blood vessel growth. Extensive studies conducted over the past few
      years have recognized that overexpression of COX-2, VEGF in the cancer might be
      the leading factors, can induce angiogenesis via induction of multiple pro
      angiogenic regulators. Breast tumor growth and metastasization are both hormone
      sensitive and angiogenesis-dependent. A single angiogenic inhibitor is not
      capable to inhibit angiogenesis. Therefore, we should select a combination of
      angiogenesis inhibitors targeting COX-2, VEGF, and bFGF pathway. This article
      reviews the background and implementation of the current use of angiogenesis
      inhibitors and discusses the likely therapeutic roles in the early and advanced
      breast cancer together with its potential for chemoprevention.

PMID- 14637392
TI  - Screening test data analysis for liver disease prediction model using growth
      curve.
AB  - This study was done based on screening test data accumulated from 1994 to 2001
      for studying of risk factor related with liver disease and prediction model of
      liver disease. In the existing study related with liver, the main current is
      studying on liver cancer, not on liver disease, previous step into liver cancer.
      As a result of estimating prediction model through the risk factors of liver
      disease and the growth curve on the basis of data, it is shown that most of the
      risk factors about liver disease are also those about known well as liver cancer.
      In addition, to investigate liver disease prevalence from the viewpoint of the
      future, this study presumed risk factor through the various growth curve analysis
      and examined logistic regression, decision tree and neural network from those
      estimators. In the case of neural network using growth curve estimator of
      Xi(5)=alphai+betaiT+epsiloniT, accuracy of liver disease was 72.55% and
      sensitivity was 78.62%. On the other hand, in the case of liver disease
      prediction model using recent screening test data estimator, accuracy was 72.09%
      and sensitivity was 71.72%. Those are lower than liver disease prediction model
      of growth curve analysis. In the various liver disease prediction models assumed
      by growth curve and many distinction models, when growth curve estimator was
      used, sensitivity value was improved.

PMID- 14637391
TI  - Polymorphisms of estrogen synthesizing and metabolizing genes and breast cancer
      risk in Japanese women.
AB  - Recent success of chemoprevention with tamoxifen has opened a new era wherein
      prevention of breast cancer is much more emphasized than treatment of established
      breast cancer. Since tamoxifen has been shown to reduce the risk of estrogen
      receptor (ER)-positive, but not ER-negative, breast cancer in the chemoprevention
      trial (P-1), it seems to be important to develop risk factors for ER-positive
      breast cancer in order to select the candidates for chemoprevention more
      appropriately. Estrogens, the major risk factors for breast cancer, are
      speculated to affect breast cancer risk through ER, thus, genetic polymorphisms
      of the genes involved in the estrogens biosynthesis and metabolism are expected
      as risk factors for ER-positive breast cancer. Significance of polymorphisms of
      the genes involved in estrogens biosynthesis (CYP17, CYP19) and metabolism
      (CYP1A1, CYP1B1, COMT) in modulating the susceptibility to breast cancer is
      reviewed. The ethnic difference of the variant allele frequencies between
      Caucasian women and Asian women is also discussed.

PMID- 14637393
TI  - How does interleukin-6 affect the membrane expressions of interleukin-6 receptor
      and gp130 and the proliferation of the human myeloma cell line OPM-2?
AB  - Interleukin-6 (IL-6) is a potent growth factor for the proliferation of multiple
      myeloma (MM), which accounts for 1-2% of all human cancers. In this study we
      investigated the effects of IL-6 in various doses on the following parameters in
      the human myeloma cell line OPM-2: membrane expression of IL-6 receptor (IL-6R)
      and gp130, proliferation of the tumour cells and the amount of the soluble IL-6
      receptor (sIL-6R) in the supernatant. Additionally, we tested the same parameters
      with the immunomodulator Viscum album (VA) extract. The expression of surface IL
      6R and gp130 was analysed by FACS, the measurements of proliferation using the
      BrdU incorporation during DNA synthesis, and the determination of sIL-6R in the
      supernatant by ELISA. OPM-2 cells proliferate spontaneously (doubling time: 48
      h), IL-6-production was not detectable. The exogenous IL-6 upregulated its own
      receptor up to a mean of 180% of controls at 5 ng/ml (P < 0.001), higher or lower
      doses were less effective. The membrane expression of gp130 was downregulated to
      1-2%. IL-6 led to increase of the sIL-6R in the supernatant (P < 0.001) and
      raised the proliferation of the myeloma cells up to a mean of 124% (P < 0.001).
      These results indicate that the human myeloma cell line OPM-2 has an autocrine IL
      6 regulation mechanism, with an additional paracrine signalling by exogenous IL
      6. This is the first report that IL-6 inhibits the membrane expression of gp130,
      although the proliferation of the myeloma cells increases. VA extract did not
      affect survival, the expression of surface receptors IL-6 and gp130 or the amount
      of sIL-6R in the supernatant. However, the proliferation of the tumour cells was
      inhibited significantly (P < 0.05) suggesting a possible arrest in the cell
      cycle.

PMID- 14638286
TI  - Interpreting abnormality: an EEG and MEG study of P50 and the auditory paired
      stimulus paradigm.
AB  - Interpretation of neurophysiological differences between control and patient
      groups on the basis of scalp-recorded event-related brain potentials (ERPs),
      although common and promising, is often complicated in the absence of information
      on the distinct neural generators contributing to the ERP, particularly
      information regarding individual differences in the generators. For example,
      while sensory gating differences frequently observed in patients with
      schizophrenia in the P50 paired-click gating paradigm are typically interpreted
      as reflecting group differences in generator source strength, differences in the
      latency and/or orientation of P50 generators may also account for observed group
      differences. The present study examined how variability in source strength,
      amplitude, or orientation affects the P50 component of the scalp-recorded ERP. In
      Experiment 1, simulations examined the effect of changes in source strength,
      orientation, or latency in superior temporal gyrus (STG) dipoles on P50 recorded
      at Cz. In Experiment 2, within- and between-subject variability in left and right
      M50 STG dipole source strength, latency, and orientation was examined in 19
      subjects. Given the frequently reported differences in left and right STG anatomy
      and function, substantial inter-subject and inter-hemispheric variability in
      these parameters were expected, with important consequences for how P50 at Cz
      reflects brain activity from relevant generators. In Experiment 1, simulated P50
      responses were computed from hypothetical left- and right-hemisphere STG
      generators, with latency, amplitude, and orientation of the generators varied
      systematically. In Experiment 2, electroencephalographic (EEG) and
      magnetoencephalographic (MEG) data were collected from 19 subjects. Generators
      were modeled from the MEG data to assess and illustrate the generator variability
      evaluated parametrically in Experiment 1. In Experiment 1, realistic amounts of
      variability in generator latency, amplitude, and orientation produced ERPs in
      which P50 scoring was compromised and interpretation complicated. In Experiment
      2, significant within and between subject variability was observed in the left
      and right hemisphere STG M50 sources. Given the variability in M50 source
      strength, orientation, and amplitude observed here in nonpatient subjects, future
      studies should examine whether group differences in P50 gating ratios typically
      observed for patient vs. control groups are specific to a particular hemisphere,
      as well as whether the group differences are due to differences in dipole source
      strength, latency, orientation, or a combination of these parameters. Present
      analyses focused on P50/M50 merely as an example of the broader need to evaluate
      scalp phenomena in light of underlying generators. The development and widespread
      use of EEG/MEG source localization methods will greatly enhance the
      interpretation and value of EEG/MEG data.

PMID- 14638287
TI  - Moderation of physiological stress responses by personality traits and daily
      hassles: less flexibility of immune system responses.
AB  - Previously we demonstrated that stressors varying on the dimension of mental
      effort and controllability have distinctive effects on cardiovascular, endocrine
      and immune system responses. The purpose of the present study was to relate
      individual differences in physiological stress responsivity to task appraisal and
      stress-induced mood changes (issue 1), trait characteristics (issue 2) and daily
      hassles (issue 3). Appraisal and mood changes did not mediate the differential
      effects of the stressors. The trait characteristics, aggression and external
      locus of control and daily hassles moderated the effect of the stressor on
      physiological parameters, especially immune parameters. Moreover, the moderation
      effect was different in the high versus the low effort stress task. High
      aggression, high external locus of control and more daily hassles were associated
      with increased reactivity in the low effort condition and decreased reactivity in
      the high effort condition, which is suggested to reflect less differentiated
      responding to changing task demands and hence, less flexibility in the immune
      system.

PMID- 14638288
TI  - Signal characteristics of spontaneous facial expressions: automatic movement in
      solitary and social smiles.
AB  - The assumption that the smile is an evolved facial display suggests that there
      may be universal features of smiling in addition to the basic facial
      configuration. We show that smiles include not only a stable configuration of
      features, but also temporally consistent movement patterns. In spontaneous smiles
      from two social contexts, duration of lip corner movement during the onset phase
      was independent of social context and the presence of other facial movements,
      including dampening. These additional movements produced variation in both peak
      and offset duration. Both onsets and offsets had dynamic properties similar to
      automatically controlled movements, with a consistent relation between maximum
      velocity and amplitude of lip corner movement in smiles from two distinct
      contexts. Despite the effects of individual and social factors on facial
      expression timing overall, consistency in onset and offset phases suggests that
      portions of the smile display are relatively stereotyped and may be automatically
      produced.

PMID- 14638289
TI  - Facilitation of heartbeat self-perception in a discrimination task with
      individual adjustment of the S+ delay values.
AB  - Thirty-two subjects (16 women, 16 men) performed two tasks that were the result
      of adapting the heartbeat perception tasks produced by Whitehead et al.
      [Biofeedback Self-Regul. 2 (1977) 371] and Katkin et al. [Psychophysiology 19
      (1982) 568], respectively. In the Whitehead task, the delay values were the
      standard 128 ms for the S+ stimulus and 384 ms for the S- stimulus after the R
      wave in one case; in the other case, the delay values were individually adjusted
      according to the median of the distribution of interval choices in an adaptation
      of the Brener and Kluvitse [Psychophysiology 25 (1988a) 554; Psychophysiology 25
      (1988b) 436] task carried out previously. In the Katkin procedure, in one case S+
      always occurred at a fixed interval (100 ms), whereas S- occurred at uniformly
      increasing intervals in relation to the R-wave. In the other case, the S+ and S-
      intervals were also individually modified according to the performance in the
      Brener and Kluvitse task. The results indicate that when the S+ values are
      individually adjusted, the sensitivity of subjects, as reflected in the
      2(arcsin(p(A)(1/2))) values, significantly improves in the Whitehead task.
      Additionally, it was seen that the performance deteriorated from the first to the
      last 50 trials, especially when the S+ values were adjusted.

PMID- 14638290
TI  - Application of the somatic marker hypothesis to individual differences in
      decision making.
AB  - The somatic marker hypothesis (Damasio, Tranel, & Damasio, 1991) is a
      controversial theory asserting that somatic activities implicitly bias human
      behavior. In this study, we examined the relationship between choice behaviors in
      the Iowa Gambling Task and patterns of skin conductance responses (SCRs) within a
      healthy population. Results showed that low SCRs for appraising the monetary
      outcome of risky decisions were related to persistence in risky choices. Such
      adherence to risky decisions was not related to poor explicit knowledge about the
      task. On the other hand, anticipatory SCRs and the effect of them on performance
      were not confirmed. Our findings suggest that a variation in covert physiological
      appraisal underlies individual differences in decision making.

PMID- 14638291
TI  - Distribution of sewage pollution around a maritime Antarctic research station
      indicated by faecal coliforms, Clostridium perfringens and faecal sterol markers.
AB  - This study describes the distribution of sewage pollution markers (faecal
      coliforms, Clostridium perfringens and faecal sterols) in seawater and marine
      sediments around Rothera Research Station, Antarctic Peninsula. Untreated sewage
      waste has been released from this site since 1975, creating the potential for
      long-term contamination of the benthic environment. Faecal coliform
      concentrations in seawater reached background levels within 300 m of the outfall.
      In sediment cores, both C. perfringens and faecal coliform concentrations
      declined with distance from the outfall, though C. perfringens persisted at
      greater depths in the sediment. High concentrations of 5beta(H)-cholestan-3beta
      ol (coprostanol) relative to the corresponding 5alpha-epimer (cholestanol),
      indicative of sewage pollution, were only found in sediments within 200 m of the
      sewage outfall. This study has shown that sewage contamination is limited to the
      immediate vicinity of the sewage outfall. Nevertheless, a sewage treatment plant
      was installed in February 2003 to reduce this contamination further.

PMID- 14638292
TI  - Studies of spatial and temporal distribution characteristics of TSP-bound trace
      metals in Seoul, Korea.
AB  - In the present study, TSP-bound metal concentrations were measured from seven
      different urbanized locations in Seoul, Korea for the period from March 2001
      through May 2002. Our measurement data were analyzed to explore the possible
      influences of spatial and temporal factors on metal distribution characteristics.
      To determine the importance of those aspects, the measured concentrations were
      compared between different metals and between different sites in terms of several
      criteria: (1) absolute concentrations and enrichment factor (EF) values; (2)
      coefficient of variation (CV) values of metal concentrations; (3) relative
      patterns of temporal variations; and (4) relative abundance of strong
      correlations. According to our analysis of metal distribution characteristics in
      the study area, the main results of our study can be summarized as follows: (1) a
      number of metals (e.g., Cd, Cu, and Pb) are highly enriched relative to the
      average crustal ratios (to Fe); (2) the behavior of Cu is found to vary
      irregularly, while Fe, Mn, and Pb are tightly coupled both spatially and
      temporally in the study area; (3) for most elements except Cu and Cd, seasonal
      variations are observed in a systematic manner; and (4) when compared against
      those observed in other parts of the world, our Cu and Cd concentrations observed
      in many locations of Seoul are notably high. The overall results of our study
      suggest that the distribution characteristics of metals can be regulated strongly
      by spatial and temporal factors and that such controls are distinguished very
      clearly between different metal types.

PMID- 14638293
TI  - The importance of biological factors affecting trace metal concentration as
      revealed from accumulation patterns in co-occurring terrestrial invertebrates.
AB  - As physicochemical properties of the soil highly influence the bioavailable
      fraction of a particular trace metal, measured metal body burdens in a particular
      species are often assumed to be more reliable estimators of the contamination of
      the biota. To test this we compared the Cd, Cu and Zn content of three spiders
      (generalist predators) and two amphipods (detritivores), co-occurring in seven
      tidal marshes along the river Schelde, between each other and with the total
      metal concentrations and the concentrations of four sequential extractions of the
      soils. Correlations were significant in only one case and significant site x
      species interactions for all metals demonstrate that factors affecting metal
      concentration were species and site specific and not solely determined by site
      specific characteristics. These results emphasize that site and species specific
      biological factors might be of the utmost importance in determining the
      contamination of the biota, at least for higher trophic levels. A hypothetical
      example clarifies these findings.

PMID- 14638294
TI  - Micro-spatial variation of soil metal pollution and plant recruitment near a
      copper smelter in Central Chile.
AB  - Soil chemical changes produced by metal smelters have mainly been studied on a
      large scale. In terms of plant survival, determination of small scale variability
      may be more important because less toxic microhabitats may represent safe sites
      for successful recruitment and thus for plant survival. Three dominant
      microhabitats (open spaces and areas below the canopy of Sphaeralcea obtusiloba
      and Baccharis linearis shrubs) were defined in a heavily polluted area near a
      copper smelter and characterised in terms of microclimate, general soil
      chemistry, total and extractable metal concentrations in the soil profile (A0
      horizon, 0-5 and 15-20 cm depth), and seedling densities. Results indicated a
      strong variability in microclimate and soil chemistry not only in the soil
      profile but also among microhabitats. Air/soil temperatures, radiation and wind
      speed were much lower under the canopy of shrubs, particularly during the plant
      growth season. Soil acidification was detected on top layers (0-5 cm depth) of
      all microhabitats while higher concentrations of N, Cu and Cd were detected on
      litter and top soil layers below shrubs when compared to open spaces; however,
      high organic matter content below shrubs decreased bioavailability of metals.
      Plant recruitment was concentrated under shrub canopies; this may be explained as
      a result of the nursery effect exerted by shrubs in terms of providing a more
      favourable microclimate, along with better soil conditions in terms of
      macronutrients and metal bioavailability.

PMID- 14638295
TI  - Effects of the mosquito larvicide GB-1111 on bird eggs.
AB  - Golden Bear Oil (GB-1111; legal trade name for GB-1313) is a petroleum distillate
      used in the United States and other countries as a mosquito larvicide. As part of
      an evaluation of the potential effects of GB-1111 on birds, fertile eggs of
      mallards (Anas platyrhynchos) and bobwhite (Colinus virginianus) were incubated
      in the laboratory, and treated on day 4 of incubation with external applications
      equivalent to either 0, 1/3, 1, 3 or 10 times the maximum rate (X) of 47 l/ha (5
      gal/A) of field application of GB-1111. Hatching success was significantly
      reduced in mallards treated at 3 and 10 times the maximum field application, with
      a calculated approximate LD50 of 1.9 times the maximum field application. Most
      mortality occurred within a week of treatment. Hepatic P450-associated
      monooxygenase activity (ethoxyresorufin-O-dealkylase; EROD) was negatively
      related to dose. In the 3X group there was a significant increase in the
      concentration of hepatic reduced glutathione (GSH) but a decrease in protein
      bound thiols (PBSH). Hatching success of bobwhite was marginally reduced at the
      highest level of treatment (10X). Other effects at this level in bobwhite
      included a significant increase in incidence of abnormal embryos or hatchlings,
      lower body and liver weights, and a two-fold increase in hepatic microsomal EROD
      activity in hatchlings. The recommended maximum rate of field application of GB
      1111 is unlikely to impair the survival or development of bobwhite embryos but is
      potentially toxic to mallard embryos under conditions of larvicide drift or spray
      overlap.

PMID- 14638296
TI  - The effects of coal dust on photosynthetic performance of the mangrove, Avicennia
      marina in Richards Bay, South Africa.
AB  - Richards Bay, on the northern KwaZulu-Natal coast, is the largest coal exporting
      port in South Africa. The coal is stored at the Richards Bay Coal Terminal (RBCT)
      prior to export. Dust from coal operations is a major problem in the Richards Bay
      area. In this study, we tested the hypothesis that coal dust adversely affects
      photosynthetic performance of Avicennia marina (Forssk.) Vierh., the dominant
      mangrove species in the harbour. Photosynthetic performance was determined on 10
      trees by measuring carbon dioxide uptake and chlorophyll fluorescence parameters
      at two elevation sites and on upper and lower leaf surfaces that were covered or
      uncovered with coal dust. Measurements were made on five clear, sunny days at
      saturating light (>1,000 micromol m(-2)s(-1)) and high temperature (28-30 degrees
      C). Coal dust significantly reduced carbon dioxide exchange of upper and lower
      leaf surfaces by 17-39%, the reduction being generally greater on the lower leaf
      surface that is covered by a dense mat of trichomes and salt glands. The
      reduction in carbon dioxide exchange by coal dust was higher at the high
      elevation site that supported isolated dwarfed trees. The chlorophyll
      fluorescence data indicated that leaves coated with dust exhibited significantly
      lower photosystem II (PS II) quantum yield, lower electron transport rate (ETR)
      through PSII and reduced quantum efficiency of PSII (FvFm). The chlorophyll
      fluorescence data supported the gas exchange measurements and are consistent with
      reduced photosynthetic performance of leaves coated with coal dust.

PMID- 14638297
TI  - Effect of food level on the acute and chronic responses of daphnids to lindane.
AB  - The toxic effects of lindane on the zooplankton communities may be strongly
      related to the population fitness, which is highly dependent on food
      availability. In order to test this hypothesis, acute (immobilisation) and
      chronic (life-history) responses of Daphnia longispina and Daphnia magna, reared
      at different food levels (low, normal, and high), were assessed in laboratorial
      exposures to several concentrations of lindane. A bifactorial design was employed
      (food level versus lindane concentration) for both species. Results showed that
      lindane was toxic to both D. magna and D. longispina, within a similar range.
      However, lindane toxicity to daphnids was dependent on food level, suggesting
      that the latter is an important factor to take into account when assessing the
      toxic effects of lindane on zooplankton communities.

PMID- 14638298
TI  - Use of cyanobacteria to assess water quality in running waters.
AB  - Epilithic cyanobacterial communities in rivers in the province of Madrid (Spain)
      and their relationship with water quality were studied. Sampling locations above
      and below outlets for sewage effluent and other wastes from human settlements
      were selected. We aimed to evaluate the use of cyanobacteria as potential
      indicators of pollution in running waters. Large increases in nutrient
      concentrations were always observed at downstream sampling sites. A decrease in
      species richness and the Margalef diversity index were associated with these
      increases in nutrient load. Differences in cyanobacterial community structure
      were also observed. A higher proportion of cyanobacteria belonging to the
      Oscillatoriales order predominated at sampling sites with higher nutrient
      content. However, Nostocales species were more abundant at upstream sites
      characterized by lower nutrient load than at downstream locations. The soluble
      reactive phosphate (SRP) had a threshold effect on cyanobacterial biomass: a
      decrease in phycobiliprotein content as SRP increased, reaching a minimum,
      followed by an increase in abundance. This increase may be attributed to
      hypertrophic conditions in those locations. Our results and literature data
      confirm the suitability of this phototroph community for monitoring
      eutrophication in rivers

PMID- 14638299
TI  - Feasibility of constructed wetlands for removing chlorothalonil and chlorpyrifos
      from aqueous mixtures.
AB  - Chlorpyrifos (an insecticide) and chlorothalonil (a fungicide) are transported in
      stormwater runoff and can be lethal to receiving aquatic system biota. This study
      determined removal rates of chlorpyrifos and chlorothalonil in simulated
      stormwater runoff treated in constructed wetland mesocosms. Using sentinel
      species, Ceriodaphnia dubia and Pimephales promelas, observed declines in
      toxicity of the simulated runoff after treatment were 98 and 100%, respectively.
      First order removal rates were 0.039/h for chlorpyrifos and 0.295/h for
      chlorothalonil in these experiments. Constructed wetland mesocosms were effective
      for decreasing concentrations of chlorpyrifos and chlorothalonil in simulated
      stormwater runoff, and decreasing P. promelas and C. dubia mortality resulting
      from these exposures. The results from this study indicate that constructed
      wetlands could be part of an efficient mitigation strategy for stormwater runoff
      containing these pesticides.

PMID- 14638300
TI  - Biomineralisation of 1,2,4-trichlorobenzene in soils by an adapted microbial
      population.
AB  - In laboratory experiments the mineralisation of 14C-labelled 1,2,4
      trichlorobenzene (1,2,4-TCB) in soils was studied by direct measurement of the
      evolved 14CO2. The degradation capacity of the indigenous microbial population
      was investigated in an agricultural soil and in a soil from a contaminated site.
      Very low mineralisation of 1% within 23 days was measured in the agricultural
      soil. Whereas in the soil from the contaminated site the mineralisation occurred
      very fast and in high rates; up to 62% of the initially applied amount of 1,2,4
      TCB were mineralised within 23 days. The transfer of the adapted microbial
      population into the agricultural soil significantly enhanced the mineralisation
      of 1,2,4-TCB in this soil, reflecting, that the transferred microbial population
      survived and maintained its degradation ability in the new microbial ecosystem.
      Additional nutrition sources ((NH4)2HPO4) increased the mineralisation rates in
      the first days significantly in the contaminated soil. In the soil from the
      contaminated site high amounts of non extractable 14C-residues were formed.

PMID- 14638301
TI  - OH-initiated oxidation of DMS/DMSO: reaction products at high NOx levels.
AB  - Dimethylsulphide (DMS) gas phase oxidation with OH radicals was investigated by
      long path FT-IR spectroscopy and by ion chromatography (IC) and HPLC-MS2 to
      quantify the reaction products and evaluate heterogeneous processes. The
      experiments were performed considering two different NOx (NO2+NO) levels. The
      initial concentration of NO2 was varied from 24 ppbV (NOx=1 ppmV) to 953 ppbV
      (NOx=10 ppmV). Photolysis of H2O2 was used as the OH-radical source. SO2,
      dimethylsulphoxide (DMSO), dimethylsulphone (DMSO2), methanesulphonic acid (MSA),
      methanesulphinic acid (MSIA) and methane sulphonyl peroxynitrate (MSPN) were
      identified as the main sulphur-containing products. The results indicate that
      higher NOx levels play a significant role in the chemistry of CH3S(O)x radical,
      influencing both the SO2/MSPN ratio and the amount of the sulphur species in the
      condensed phase, and that the NO2/NO ratio could influence the trends in the
      molar yields of the different products. For this reason the NOx content results a
      limiting parameter when on measure DMS in atmospheric environment.

PMID- 14638303
TI  - Biodegradation of nonylphenol in river sediment.
AB  - We investigated the biodegradation of nonylphenol monoethoxylate (NP1EO) and
      nonylphenol (NP) by aerobic microbes in sediment samples collected at four sites
      along the Erren River in southern Taiwan. Aerobic degradation rate constants (k1)
      and half-lives (t1/2) for NP (2 microg g(-1)) ranged from 0.007 to 0.051 day(-1)
      and 13.6 to 99.0 days, respectively; for NP1EO (2 microg g(-1)) the ranges were
      0.006 to 0.010 day(-1) and 69.3 to 115.5 days. Aerobic degradation rates for NP
      and NP1EO were enhanced by shaking and increased temperature, and delayed by the
      addition of Pb, Cd, Cu, Zn, phthalic acid esters (PAEs), and NaCl, as well as by
      reduced levels of ammonium, phosphate, and sulfate. Of the microorganism strains
      isolated from the sediment samples, we found that strain JC1 (identified as
      Pseudomonas sp.) expressed the best biodegrading ability. Also noted was the
      presence of 4'-amino-acetophenone, an intermediate product resulting from the
      aerobic degradation of NP by Pseudomonas sp.

PMID- 14638302
TI  - Organochlorine concentrations in diseased vs. healthy gull chicks from the
      northern Baltic.
AB  - The population decline of the nominate lesser black-backed gull Larus fuscus
      fuscus in the Gulf of Finland (northern Baltic) is caused by an exceedingly high
      chick mortality due to diseases. The chick diseases include degeneration in
      various internal organs (primarily liver), inflammations (mainly intestinal), and
      sepsis, the final cause of death. The hypothesis of starvation causing intestinal
      inflammations (leading to sepsis) was tested by attempting to reproduce lesions
      in apparently healthy herring gull L. argentatus chicks in captivity. The herring
      gull chicks were provided a similar low food-intake frequency as observed for the
      diseased chicks in the wild. However, empty alimentary tract per se did not
      induce the intestinal inflammations and therefore, inflammations seem to be
      innate or caused by other environmental factors in the diseased lesser black
      backed chicks. They had very high concentrations of PCB in their liver; but the
      concentrations were not significantly higher than those of the healthy herring
      gull chicks, indicating a common exposure area for both species (i.e. the Baltic
      Sea). When compared to NOEL and LOEL values for TEQs in bird eggs our TEQ levels
      clearly exceed most or all of the values associated with effects. Compared with
      published data on fish-eating waterbirds, the DDE concentrations in the diseased
      lesser black-backed chicks were well above the levels previously correlated with
      decreased reproduction, while the residues in apparently healthy herring gulls
      were below those levels. The DDE/PCB ratio in lesser black-backs was
      significantly elevated, indicating an increased exposure to DDTs as compared with
      most other Baltic and circumpolar seabirds. The possible exposure areas of DDT in
      relation to differential migration habits of the two gull species are discussed.

PMID- 14638304
TI  - Dynamics of microcystins-LR and -RR in the phytoplanktivorous silver carp in a
      sub-chronic toxicity experiment.
AB  - A sub-chronic toxicity experiment was conducted to examine tissue distribution
      and depuration of two microcystins (microcystin-LR and microcystin -RR) in the
      phytoplanktivorous filter-feeding silver carp during a course of 80 days. Two
      large tanks (A, B) were used, and in Tank A, the fish were fed naturally with
      fresh Microcystis viridis cells (collected from a eutrophic pond) throughout the
      experiment, while in Tank B, the food of the fish were M. viridis cells for the
      first 40 days and then changed to artificial carp feed. High Performance Liquid
      Chromatography (HPLC) was used to measure MC-LR and MC-RR in the M. viridis
      cells, the seston, and the intestine, blood, liver and muscle tissue of silver
      carp at an interval of 20 days. MC-RR and MC-LR in the collected Microcystis
      cells varied between 268-580 and 110-292 microg g(-1) DW, respectively. In Tank
      A, MC-RR and MC-LR varied between 41.5-99.5 and 6.9-15.8 microg g(-1) DW in the
      seston, respectively. The maximum MC-RR in the blood, liver and muscle of the
      fish was 49.7, 17.8 and 1.77 microg g(-1) DW, respectively. No MC-LR was
      detectable in the muscle and blood samples of the silver carp in spite of the
      abundant presence of this toxin in the intestines (for the liver, there was only
      one case when a relatively minor quantity was detected). These findings contrast
      with previous experimental results on rainbow trout. Perhaps silver carp has a
      mechanism to degrade MC-LR actively and to inhibit MC-LR transportation across
      the intestines. The depuration of MC-RR concentrations occurred slowly than
      uptakes in blood, liver and muscle, and the depuration rate was in the order of
      blood>liver>muscle. The grazing ability of silver carp on toxic cyanobacteria
      suggests an applicability of using phytoplanktivorous fish to counteract
      cyanotoxin contamination in eutrophic waters.

PMID- 14638305
TI  - The use of light and electron microscopy to assess the impact of ozone on Norway
      spruce needles.
AB  - Light (LM) and transmission electron (TEM) microscopy were used to study
      previously specified ozone symptoms in the foliage of Norway spruce. The three
      youngest green needle generations from twenty mature trees in two stands on sites
      of different soil fertility at Asa, southern Sweden, were sampled in 1999. The
      critical dose of ozone, expressed as AOT40, was 6,362 ppb.h. LM showed ozone
      specific symptoms: decreased chloroplast size with electron dense stroma
      advancing gradually from the outer to the inner cell layers, being most severe in
      the needle side facing the sky. The symptoms were expressed as ozone syndrome
      indices at the needle generation, tree and stand levels. The index had higher
      values at the low fertility site. TEM was used to confirm the LM results. The
      study shows that LM can be used for diagnosis of the impact of ozone on conifers
      in the field.

PMID- 14638306
TI  - Accumulation history of radionuclides in the lichen Stereocaulon vesuvianum from
      Mt. Vesuvius (south Italy).
AB  - The fruticose lichen Stereocaulon vesuvianum, growing on the slopes of Mt.
      Vesuvius (south Italy), was used as a biomonitor of 134Cs, 137Cs, 103Ru and 106Ru
      derived from the April 26 1986 Chernobyl nuclear reactor accident. Samples were
      taken at five different quotes (370, 490, 580, 780 and 960 m a.s.l.) and four
      successive dates (October 1986, December 1986, October 1987 and May 1999). At the
      first sampling, the concentrations (as Bq kg(-1) dry weight) ranged between 460
      and 1020 for 134Cs, 1330 and 2500 for 137Cs, 90 and 200 for 103Ru and 360 and 710
      for 106Ru, values generally lower in respect to those measured in soil and higher
      plants. Of the total 137Cs measured only 14% was due to 1950s and 1960s nuclear
      weapons tests fallout. Highest average activities of all nuclides were observed
      at the quote of 960 m and significant correlation (0.7<r(2)<0.9) with altitude
      was found for 106Ru and 137Cs values. The time span between the first two
      samplings (38 days) was enough to highlight only the decay of 103Ru (T1/2=40
      days). At sampling performed 1 year later (October 1987) only 134Cs, 137Cs, and
      106Ru were observed. Thirteen years after the Chernobyl incident (May 1999),
      although a decrease was obvious with time, the 137Cs content in lichen thallus
      was still appreciable (270-570 Bq kg(-1) dw). Experimental results from the first
      three samplings yield effective residence time of 0.98+/-0.07, 5.9+/-0.3 and
      1.6+/-0.1 years for 106Ru, 137Cs and 134Cs, respectively. The last sampling of
      May 1999 allowed to achieve a more precise determination of lifetime of 137Cs
      (6.1+/-0.4 years).

PMID- 14638307
TI  - Sympathetic and brain monoaminergic regulation of energy balance in obesity
      resistant rats (Lou/C).
AB  - In contrast to the Wistar rat, the Lou/C rat does not develop obesity with age.
      To determine the role of sympathetic output and brain monoamines in the different
      energy balance of Lou/C rats, the monoamine contents and activity of rate
      limiting enzymes in catecholamine and serotonin biosynthesis were assessed in
      brain structures involved in energy balance regulation, i.e., brainstem
      noradrenergic (A6, A5, A2) and serotonergic cell groups (dorsal raphe, and median
      raphe), and two hypothalamic nuclei (ventromedial nucleus and paraventricular
      nucleus). In vivo tyrosine hydroxylase activity and noradrenaline content were
      measured in sympathetic target organs storing fuel substrates, the liver, white
      adipose and brown adipose tissues in the Lou/C rat and compared to the Wistar
      rat. In Lou/C rats, indirect calorimetric measurements showed a higher energy
      expenditure despite a reduced food intake. The Lou/C rat displayed selective
      monoamine features. The catecholaminergic activity was higher in the white
      adipose tissue and interscapular brown adipose tissue but lower in the liver and
      adrenal gland of Lou/C rats. The noradrenergic activity in A2, A6 and
      ventromedial nucleus, and the serotonergic pattern in A6, dorsal raphe and median
      raphe were lower in Lou/C. The metabolic particularities of Lou/C rats are
      associated with (i) a selectively enhanced sympathetic activity restricted to the
      white adipose tissue and brown adipose tissue, (ii) a reduced noradrenergic
      activity in selective brainstem and hypothalamic areas, which control the energy
      expenditure and food intake.

PMID- 14638308
TI  - Afferent pathways and responses of T3-T4 spinal neurons to cervical and thoracic
      esophageal distensions in rats.
AB  - The purposes of this study were to (1) compare responses of T(3)-T(4) spinal
      neurons to thoracic and cervical esophageal distension (TED, CED) and (2)
      determine afferent pathways for esophageal input to these neurons. Extracellular
      potentials of single superficial and deeper T(3)-T(4) neurons were recorded in
      pentobarbital anesthetized male rats. Graded TED or CED was produced by water
      inflation (0.1-0.5 ml) of a latex balloon. TED changed activity of 121/432 (28%)
      neurons (114 were excited); CED activated 69/269 (26%) neurons (56 were excited).
      Of 151 neurons that were tested for responses to both TED and CED, 40 (26%)
      neurons responded to both TED and CED. Mean duration of excitatory responses in
      convergent neurons to TED was significantly longer than the duration of responses
      to CED (31.4+/-2.8 vs. 25.4+/-1.0 s, n=34, P<0.05). A total of 105 out of 121
      (87%) and 66 out of 69 (96%) neurons responsive to TED and CED had somatic
      fields. Spinal transection at rostral C(1) and at C(7)-C(8) indicated that
      excitatory responses to TED resulted from activation of afferent input that
      entered thoracic spinal segments; whereas, excitatory responses to CED resulted
      from afferent inputs entering cervical or thoracic spinal segments. These data
      showed that the upper thoracic spinal cord received sensory information from the
      esophagus through cervical and/or thoracic spinal visceral afferent pathways.

PMID- 14638309
TI  - Blockade of N-methyl-D-aspartate receptors within the rostral ventrolateral
      medulla antagonizes clonidine-induced cardiovascular effects.
AB  - There is wide agreement that the rostral ventrolateral medulla (RVLM) plays a
      crucial role in the regulation of blood pressure (BP), and that there may be a
      close correlation between the actions of centrally acting antihypertensive agents
      and N-methyl-D-aspartate (NMDA) receptor functional states. The present study was
      done to test the hypothesis that NMDA receptors within the RVLM were involved in
      the cardiovascular effects of centrally acting antihypertensive drug clonidine in
      anesthetized and paralyzed rats. Prior unilateral microinjection of NMDA receptor
      antagonist dizocilpine (MK801, 500 pmol) into the RVLM significantly attenuated
      (p<0.01, n=9) the reductions of BP (-24+/-6 to -8+/-4 mm Hg) and heart rate (
      49+/-9 to -14+/-7 bpm) induced by unilaterally injected clonidine (5 nmol) into
      the RVLM. Prior bilateral microinjection of MK801 (500 pmol for each side) into
      the RVLM effectively (p<0.01, n=7) antagonized the hypotension (-25+/-5 to -8+/-2
      mm Hg) and bradycardia (-43+/-7 to -11+/-4 bpm) of intravenously administered
      clonidine (10 microg kg(-1)). Importantly, iontophoretic application of MK801 (60
      nA) significantly (p<0.01, n=9) prevented the inhibitory effect of intravenously
      (10 microg kg(-1)) injected clonidine on the discharge of presympathetic neurons
      in the RVLM (neuronal inhibition: -39+/-6 to -10+/-2%). In conclusion, the
      present study shows that the RVLM administrated MK801 effectively antagonizes
      clonidine-induced cardiovascular effects, and suggests that NMDA receptors within
      the RVLM contribute to clonidine actions.

PMID- 14638310
TI  - The pattern of norepinephrine release in the hypothalamic paraventricular nucleus
      in response to repeated peripheral nerve injury differs in the acute and chronic
      stage in conscious rats.
AB  - We investigated the change in norepinephrine (NE) release in the hypothalamic
      paraventricular nucleus (PVN) in response to ligature of the median and ulnar
      nerves using a brain microdialysis technique in conscious rats. Primary ligature
      was performed of the right median and ulnar nerves, and then repeated injury was
      performed on the left nerves 6 h or 3 weeks after the primary ligature. Primary
      ligature of the nerves produced a significant increase that peaked at a mean 330%
      above basal NE release in the first 20 min. The NE release after reinjury 6 h
      later was significantly higher (a peak of 650%) than after primary nerve injury,
      although that at 3 weeks was significantly lower (a peak of 280%). The present
      study demonstrated that peripheral nerve injury induces an elevated response of
      the PVN, which is an integral center of the autonomic nervous system. NE release
      after reinjury differed in the acute and chronic stages.

PMID- 14638311
TI  - Sensory but not parasympathetic nerves are required for ocular vascular
      remodeling following chronic sympathectomy in rat.
AB  - Choroidal vascularity increases following chronic sympathetic denervation in
      rats. The mechanisms of this remodeling are unclear. Since both nitric oxide and
      substance P/CGRP have been suggested as angiogenic factors in other targets, we
      hypothesized that sensory or parasympathetic nerves may also participate in
      ocular vascular remodeling. To test this hypothesis, sympathetic denervation was
      accomplished by superior cervical ganglionectomy. Sensory denervation was induced
      by subcutaneous injections of capsaicin on postnatal days 2 and 9, and ocular
      parasympathetic innervation was ablated by pterygopalatine ganglion excision on
      postnatal day 60. Eyes were processed and sectioned for light microscopic
      histomorphometry. Sympathetic denervation for 6 weeks resulted in increased
      choroidal thickness, vascular luminal area, numbers of large venules and large
      arterioles, and capillaries in the outer nuclear layer. Capsaicin pretreatment
      prevented sympathectomy-induced increases in choroidal thickness, vascular
      luminal area and large venules and large arterioles, whereas pterygopalatine
      ganglionectomy was without effect. Both sensory and parasympathetic denervation
      attenuated increases in outer nuclear layer capillaries. These studies indicate
      that increased choroidal vascularity noted after chronic sympathectomy requires
      intact sensory innervation.

PMID- 14638312
TI  - Parametric description of cardiac vagal control.
AB  - Heart rate variability (HRV) indices that reflect the magnitude of respiratory
      sinus arrhythmia (RSA) are commonly applied as non-invasive measures of cardiac
      vagal control. Recently, however, serious doubts have been raised about the
      accuracy and validity of such assessments. To evaluate these methods, we derived
      a theoretical model for the dependence of mean heart rate and RSA on gradual
      vagal blockade by atropine, and compared its predictions to actual experimental
      results. The experiment involved the injection of nine consecutive intravenous
      bolus doses of atropine to eight young healthy male subjects. Seven-minute
      recordings of ECG and respiration were made for each atropine dose. The heart
      rate (HR) signal was derived from the ECG recording, and mean heart rate and the
      power of the high frequency peak of HRV (which measures the magnitude of RSA)
      were computed. The experimental data were fitted to the model's equations, and
      optimal values were obtained for the model's parameters. A tight agreement is
      observed between the theoretical fitted curves and the experimental data. The
      parameters that were computed from fitting the experimental data to the mean
      heart rate equation display a surprisingly small variance among the different
      subjects. The parameters that were computed from fitting the experimental data to
      the RSA equation, and the resulting shape of these fitted curves, explain many of
      the conflicting results previously published, and provide a new quantitative
      insight to cardiac vagal activity.

PMID- 14638313
TI  - Stellate ganglion block increases blood flow into the optic nerve head and the
      peripapillary retina in human.
AB  - The effects of stellate ganglion block (SGB) on the blood flow of the optic nerve
      head (ONH) and the peripapillary retina, which plays an important role in the
      pathogenesis of a major blinding disease, e.g. glaucoma, are unclear. The aim of
      this study was to evaluate the effects of a sympathetic block on the blood flow
      of the ONH and the peripapillary retina. Heidelberg Retinal Flowmetry, which is a
      system incorporating a noninvasive confocal scanning laser Doppler flow meter,
      was used to measure the retinal blood flow. A unilateral stellate ganglion block
      was performed in 11 healthy subjects. The retinal blood flows were measured
      before, 30 and 120 min after SGB. On each occasion, three scans were obtained and
      the blood flow was analyzed. The systemic blood pressure (BP) and the intraocular
      pressure (IOP) were also measured at the set time points. The blood flow of the
      ONH and the peripapillary retina of the ipsilateral retina was significantly
      increased (P=0.001) by 106.8% and 98.7%, respectively, 30 min after SGB without
      accompanying significant changes in BP and IOP when compared to their baseline
      values; while those of the contralateral eyes did not change. The effect of SGB
      on blood flow in these areas disappeared 120 min after SGB. In conclusion, SGB
      may have a beneficial effect on ocular diseases associated with ischemia of the
      ONH and the peripapillary retina, e.g. glaucoma.

PMID- 14638314
TI  - Genomes and evolution. From sequence to organism.

PMID- 14638315
TI  - Mutation rate variation in the mammalian genome.
AB  - Recent advances in the large-scale sequencing of mammalian genomes have provided
      a means to study divergence in not only genic sequences but also in the non
      coding bulk of DNA. There is evidence of significant variation in the levels of
      divergence between presumably neutral regions, pointing at an underlying
      variation in the rate of mutation across the genome. Apparently, such variation
      occurs on different scales, including sequence context effects (the influence of
      neighboring nucleotides on the rate of mutation at individual sites), variation
      within chromosomes (on the scales of kilobases as well as megabases), and between
      chromosomes (among autosomes as well as between autosomes and sex chromosomes).
      An important aspect for further research in this area is to study whether there
      is an ultimate evolutionary explanation for mutation rate variation within
      mammalian genomes.

PMID- 14638316
TI  - Role of evolutionary history on haplotype block structure in the human genome:
      implications for disease mapping.
AB  - With the completion of the first draft of the human genome sequencing project, a
      new challenge is to characterize patterns of linkage disequilibrium and haplotype
      structure across genomic regions to identify mutations associated with complex
      disease. Recent work shows considerable linkage disequilibrium heterogeneity,
      where genomic regions of extended haplotype blocks are punctuated by
      recombination hotspots. In this review we explore some of the current approaches
      to defining and characterizing 'hapblocks', mechanisms by which hapblocks may be
      generated, and the implications this block-like structure may have for
      successfully mapping mutations associated with complex disease.

PMID- 14638317
TI  - Genomic approaches to analyzing natural variation in Arabidopsis thaliana.
AB  - The genomics tools available for studying Arabidopsis thaliana are a great
      resource for researchers trying to characterize and understand the genetic basis
      of natural variation. Abundant polymorphic markers aid quantitative trait locus
      (QTL) mapping, the fully sequenced genome provides rapid identification of
      candidate loci, and extensive knockout collections allow those candidate loci to
      be tested. Combining QTL mapping of classic phenotypic traits with biochemical or
      expression analysis is providing mechanistic insight into the traits of interest.
      Conversely, natural variation studies are now being done on genomic traits such
      as methylation or chiasma frequency.

PMID- 14638318
TI  - Rearrangements and chromosomal evolution.
AB  - Comparisons of the genome sequences of related species suggests varying patterns
      of chromosomal rearrangements in different evolutionary lineages. In this review,
      I focus on the quantitative characterization of rearrangement processes and
      discuss specific inventories that have been compiled to date. Of particular
      interest are the statistical distribution of the lengths of inverted or locally
      transposed chromosome fragments (notably very short ones), inhomogeneities in
      susceptibility to evolutionary breakpoints in chromosomal regions, the relative
      importance of genome doubling in the history of multicellular eukaryotes, and of
      lateral transfer versus gene gain and loss in prokaryotes. These developments
      provide challenges to computational biologists to refine, revise and scale up
      mathematical models and algorithms for analyzing genome rearrangements.

PMID- 14638319
TI  - Evolution and diversity of fish genomes.
AB  - The ray-finned fishes ('fishes') vary widely in genome size, morphology and
      adaptations. Teleosts, which comprise approximately 23600 species, constitute
      >99% of living fishes. The radiation of teleosts has been attributed to a genome
      duplication event, which is proposed to have occurred in an ancient teleost. But
      more evidence is required to support the genome-duplication hypothesis and to
      establish a causal relationship between additional genes and teleost diversity.
      Fish genomes seem to be 'plastic' in comparison with other vertebrate genomes
      because genetic changes, such as polyploidization, gene duplications, gain of
      spliceosomal introns and speciation, are more frequent in fishes.

PMID- 14638320
TI  - Hox gene evolution in nematodes: novelty conserved.
AB  - The conserved homeobox (Hox) gene cluster is neither conserved nor clustered in
      the nematode Caenorhabditis elegans. Instead, C. elegans has a reduced and
      dispersed gene complement that is the result the loss of Hox genes in stages
      throughout its evolutionary history. The roles of Hox genes in patterning the
      nematode body axis are also divergent, although there are tantalising remnants of
      ancient regulatory systems. Hox patterning also differs greatly between C.
      elegans and a second 'model' nematode, Pristionchus pacificus. The pattern of Hox
      gene evolution may be indicative of the move to deterministic developmental modes
      in nematodes.

PMID- 14638321
TI  - The evolution of multicellularity and early animal genomes.
AB  - Several independent molecular datasets, including complete mtDNA sequence,
      indicate that Choanozoa are most closely related to multicellular animals. There
      is still confusion concerning basal animal phylogeny, although recent data
      indicate that Placozoa are not degenerate cnidarians and hence (along with
      sponges) occupy a pivotal position. The transition in evolution from diploblast
      to bilaterian animals is becoming better understood, with gene expression data
      arguing that cnidarians have forerunners of the anteroposterior and dorsoventral
      body axes, and even a putative homologue of mesoderm. The homeobox and kinase
      gene families have been further analysed in basal animals, although more data are
      required to enable detailed comparison with Bilateria.

PMID- 14638322
TI  - Genomic regulatory regions: insights from comparative sequence analysis.
AB  - Comparative sequence analysis is contributing to the identification and
      characterization of genomic regulatory regions with functional roles. It is
      effective because functionally important regions tend to evolve at a slower rate
      than do less important regions. The choice of species for comparative analysis is
      crucial: shared ancestry of a clade of species facilitates the discovery of
      genomic features important to that clade, whereas increased sequence divergence
      improves the resolution at which features can be discovered. Recent studies
      suggest that comparative analyses are useful for all branches of life and that,
      in the near future, large-scale mammalian comparative sequence analysis will
      provide the best approach for the comprehensive discovery of human regulatory
      elements.

PMID- 14638323
TI  - Dissecting the transcription networks of a cell using computational genomics.
AB  - A great challenge in understanding biological complexity in the post-genome era
      is to reconstruct the regulatory networks governing the patterns of gene
      expression. In the past few years, the rapid accumulation of genomic sequence and
      functional data has led to the development of computational approaches to
      systematically dissect transcriptional regulatory networks. Effective algorithms
      have been developed to predict cis-regulatory elements in a genome, to identify
      the target genes of transcription factors, to infer the conditions under which
      each transcription factor is either activated or deactivated, and to analyze
      combinatorial regulation by multiple transcription factors. Genomic approaches
      have profoundly changed the way biologists investigate transcriptional
      regulation, and global pictures of the transcription networks for several model
      organisms are beginning to emerge.

PMID- 14638324
TI  - Adaptive evolution of genes and gene families.
AB  - The huge influx of genomic sequence and new statistical methods is making the
      discovery of genes subjected to adaptive evolution increasingly common. The use
      of comparative genomics to identify adaptive evolution is resulting in
      predictions of functionally important genes and gene regions. However, the
      selective pressure driving the adaptive evolution of most genes remains
      mysterious.

PMID- 14638325
TI  - Eukaryotic domain evolution inferred from genome comparisons.
AB  - Comparative analyses of eukaryotic genomes are providing insights into the mode
      and tempo of domain family evolution. Gene duplication, the source of family
      expansion, far exceeds the rate of emergence of domains from non-coding sequence,
      and the rate of recruitment of domains into novel architectures. Domain families
      that appear to be restricted to certain lineages are likely to be the result of
      gene duplication, coupled with rapid sequence diversification. If such families
      are evidence of past adaptation, then their functions must relate to the
      underlying mechanism of selection: competition among organisms.

PMID- 14638326
TI  - Duplicate, decouple, disperse: the evolutionary transience of human centromeric
      regions.
AB  - Human centromeric regions are enriched for segmental duplications, which
      elsewhere in the genome precipitate both genetic disease and gene formation.
      Molecular cytogenetic analyses of primate chromosomes have established that
      centromeres frequently move without altering the surrounding gene order.
      Recently, the positions of two ancestral centromeres have been mapped to regions
      of the human genome that are both rich in segmental duplications and are
      associated with duplication-based clinical phenotypes. This suggests a model for
      the evolution of euchromatic segmental duplication families involving the
      localised elevation of recombination rates within the duplication-rich
      heterochromatin of recently inactivated centromeres, and raises the possibility
      that the distribution of duplication/deletion syndromes within our genome has
      been heavily influenced by such events. The relaxation of the heterochromatin
      environment that must accompany centromere inactivation would also increase the
      transcriptional activity within previously pericentromeric DNA, increasing the
      likelihood of chimaeric gene creation through pericentromeric-directed
      duplication events.

PMID- 14638327
TI  - Turning the clock back on ancient genome duplication.
AB  - Complete genome sequence data led rapidly to the conclusion that ancient genome
      duplications had shaped the genomes of the model organisms Saccharomyces
      cerevisiae and Arabidopsis thaliana. Recent contributions have gone on to refine
      date estimates for these duplications and, in the case of Arabidopsis, to infer
      additional, more ancient, rounds of duplication by reconstructing gene order
      before the most recent duplication event. It is becoming widely accepted that an
      ancient duplication occurred before the radiation of the ray-finned fish.
      However, despite methodological advances and the availability of complete genome
      sequence data the debate over whether very ancient genome duplications have
      occurred early in the vertebrate lineage has not yet been fully resolved.

PMID- 14638328
TI  - Structure and evolution of cereal genomes.
AB  - The cereal species, of central importance to our diet, began to diverge 50-70
      million years ago. For the past few thousand years, these species have undergone
      largely parallel selection regimes associated with domestication and improvement.
      The rice genome sequence provides a platform for organizing information about
      diverse cereals, and together with genetic maps and sequence samples from other
      cereals is yielding new insights into both the shared and the independent
      dimensions of cereal evolution. New data and population-based approaches are
      identifying genes that have been involved in cereal improvement. Reduced
      representation sequencing promises to accelerate gene discovery in many large
      genome cereals, and to better link the under-explored genomes of 'orphan' cereals
      with state-of-the-art knowledge.

PMID- 14638329
TI  - Mobile elements and mammalian genome evolution.
AB  - Mobile elements make up large portions of most eukaryotic genomes. They create
      genetic instability, not only through insertional mutation but also by
      contributing recombination substrates, both during and long after their
      insertion. The combination of whole-genome sequences and the development of
      innovative new assays to test the function of mobile elements have increased our
      understanding of how these elements mobilize and how their insertion impacts
      genome diversity and human disease.

PMID- 14638330
TI  - Antireflux surgery: who needs it?

PMID- 14638331
TI  - Ultrathin endoscopy without sedation: is this the future of esophagology?

PMID- 14638332
TI  - Erythropoietin for ribavirin-induced anemia in hepatitis C: more answers but many
      more questions.

PMID- 14638333
TI  - Vitamins E and C for the treatment of NASH: duplication of results but lack of
      demonstration of efficacy.

PMID- 14638334
TI  - Economic and clinical effects of evaluating rapid viral response to peginterferon
      alfa-2b plus ribavirin for the initial treatment of chronic hepatitis C.
AB  - OBJECTIVES: Evaluation of 12-wk viral response to initial antiviral therapy for
      chronic hepatitis C has been recommended to minimize antiviral-associated
      morbidity and costs. The aim of this study was to examine the economic and
      clinical effects of evaluating rapid viral response during antiviral therapy for
      treatment naive chronic hepatitis C patients. METHODS: We applied viral response
      and drug dosage from an international randomized clinical trial of ribavirin plus
      peginterferon alfa-2b or ribavirin plus interferon alfa-2b to a previously
      published computer cohort simulation to project lifelong clinical and economic
      outcomes. Natural history and economic estimates were based on published
      literature, expert panel estimates, and actual variable and reimbursement cost
      data. RESULTS: The assessment of 12-wk rapid viral response reduced antiviral
      treatment duration by 40-44% and antiviral costs by 44-45% (savings of $15,116
      16,268 for peginterferon plus ribavirin and $8300 for interferon plus ribavirin)
      compared to full 48-wk dosing. With the 12-wk evaluation, the marginal cost
      effectiveness of peginterferon plus ribavirin versus interferon plus ribavirin
      was $13,600-22,800 compared with $14,600-25,000 per discounted quality adjusted
      life-year gained with the 24-wk evaluation. For genotype 1, hepatitis C infected
      patients, 12-wk testing for peginterferon plus ribavirin remaining preferred and
      cost-effective compared with interferon plus ribavirin. For genotype 2 or 3,
      hepatitis C infected patients, 12-wk testing yielded similar results to those of
      24-wk treatment. CONCLUSIONS: Assessment of 12-wk viral response in genotype 1,
      hepatitis C infected patients should reduce peginterferon plus ribavirin
      morbidity and costs and improve its cost-effectiveness; however, for genotype 2
      and 3, hepatitis C infected patients, 12-wk testing and 24-wk treatment have
      similar outcomes. Decisions regarding continuation of antiviral treatment should
      also consider the variability in the accuracy of quantitative viral assays as
      well as patient preferences and other potential benefits of the same treatments.

PMID- 14638335
TI  - A new look at toxic megacolon: an update and review of incidence, etiology,
      pathogenesis, and management.
AB  - Toxic megacolon (TM) is an infrequent but devastating complication of colitis.
      Numerous forms of colonic inflammation can give rise to TM but the majority occur
      in individuals with inflammatory bowel disease (IBD). Recently there has been a
      marked increase in the number of reports of TM associated with pseudomembranous
      colitis. Because of the associated high morbidity and mortality, early
      recognition and management of TM is of paramount importance. The mechanisms
      involved in development of TM are not clearly delineated, but chemical mediators
      such as nitric oxide and interleukins may play a pivotal role in the
      pathogenesis. New evidence suggests that TM and its associated morbidity may be
      predicted by the extent of small bowel and gastric distension in patients with
      colitis. CT scanning may also play an important role the management of TM, in
      that it may be the only noninvasive mode to detect subclinical perforations and
      abscesses. Management involves close medical attention, supportive care, and
      treatment of the underlying colitis. Possible exacerbating factors such as
      narcotic and anticholinergic medications must be withdrawn, and colonic
      decompression via tube drainage or positional techniques must be considered.
      Signs of progression or complications of the disease must be treated aggressively
      with surgical intervention, as delay is associated with even greater risk of
      mortality.

PMID- 14638336
TI  - Novel approaches to treating inflammatory bowel disease: targeting alpha-4
      integrin.
AB  - Crohn's disease involves persistent recruitment of leukocytes into gut tissue,
      coupled with dysregulated activation of specific immune cell function. Adhesion
      molecules expressed by circulating leukocytes, such as alpha 4 integrin, mediate
      their attachment to vascular endothelial cells lining blood vessels within the
      intestine and facilitate their migration into the tissue. Through interactions
      with extracellular matrix molecules, adhesion molecules then support immune cell
      activation and survival within the intestinal wall. Agents that interfere with
      these adhesive interactions hold great potential for suppressing the cycle of
      leukocyte infiltration and activation, and thereby, for ameliorating chronic
      inflammation. This article will discuss clinical data for a humanized monoclonal
      antibody against alpha 4 integrin, natalizumab, which is the first alpha 4
      integrin antagonist in a new class of biotechnology agents referred to as
      selective adhesion molecule inhibitors.

PMID- 14638337
TI  - A prospective, blinded study of diagnostic esophagoscopy with a superthin, stand
      alone, battery-powered esophagoscope.
AB  - OBJECTIVES: A more widely available, well-tolerated, and cost-effective technique
      is needed to screen a broad population at risk for esophageal cancer. An ideal
      solution might be to perform unsedated esophagoscopy with an entirely self
      contained, small-caliber endoscope. In a prospective, blinded study in three
      phases, we compared the feasibility, patient tolerance, and diagnostic accuracy
      of esophagoscopy performed with a prototype, superthin, battery-powered
      esophagoscope (BPE) with standard video esophagogastroduodenoscopy (SVE).
      METHODS: In phase I, 10 healthy volunteers underwent both peroral and transnasal
      esophagoscopy with BPE to evaluate the technical feasibility of the examination.
      For phases II and III, patients were recruited to have BPE before SVE. In phase
      II, both procedures were performed with conscious sedation. In phase III, the BPE
      was performed with only topical anesthesia. Two endoscopists assessed the
      technical performance of the endoscope and patient tolerance and recorded the
      esophageal findings independently. RESULTS: In phase I, all endoscopists reported
      adequate visualization of the esophagus in the 10 volunteers. A total of 181
      patients were evaluated in phases II and III (89 in phase II, 92 in phase III).
      The sensitivity for detecting columnar lined esophagus was 94% in phase II and
      95% in phase III. The sensitivity for all esophageal findings was 87% and 86% in
      phases II and III, respectively. The technical performance of the endoscope was
      significantly worse for BPE compared with the SVE. The patient tolerance as
      evaluated by the endoscopist was similar for both procedures. Ninety-five percent
      of the patients undergoing unsedated BPE were willing to have the procedure
      repeated under similar circumstances. CONCLUSIONS: Unsedated esophagoscopy with a
      3.1-mm, battery-powered, stand-alone esophagoscope is feasible, well tolerated,
      and accurate in detecting esophageal pathologies. It might be an efficient and
      cost-effective screening tool for the detection of columnar lined esophagus.

PMID- 14638338
TI  - Does a surgical antireflux procedure decrease the incidence of esophageal
      adenocarcinoma in Barrett's esophagus? A meta-analysis.
AB  - OBJECTIVE: The risk of adenocarcinoma of the esophagus is increased among those
      with Barrett's esophagus (BE). Whether the risk of cancer in the setting of BE
      can be decreased by a surgical antireflux procedure (SARP) is unclear. This study
      compared the reported incidence of esophageal adenocarcinoma in subjects with BE
      who underwent SARP with those with BE who had medical management. METHODS: We
      used MEDLINE to perform a meta-analysis of the English language literature
      published from 1966 through October 2001. We reviewed abstracts found with the
      search term "Barrett's esophagus" and the following: "adenocarcinoma,"
      "esophageal neoplasm," "proton pump inhibitor," "fundoplication," or "antireflux
      procedure." Study entry criteria included 1) trial or cohort study with a report
      of cancer risk expressible in cancers per patient-year, 2) histologic
      confirmation of BE and any adenocarcinomas, and 3) adequate description of
      intervention (medical vs SARP). Data were abstracted by two reviewers using
      standardized forms. Subgroup comparisons were made using only medical management
      studies published in the last 5 yr. Multivariable regression controlling for
      subject age, country of origin, and BE length was performed. RESULTS: We reviewed
      1247 abstracts, and 34 met the inclusion criteria. There were a cumulative 4678
      patient-years of follow-up in the SARP group and 4906 patient-years in the
      medical group. The cancer incidence rate in the SARP group was 3.8 cancers/1000
      patient-years, compared with 5.3 in the medical group (p=0.29). Similarly, there
      was no significant difference between cancer rates when comparing SARP with
      medical series reported in the last 5 yr (3.8/1000 patient-years vs 4.2/1000
      patient-years, p=0.33). Multivariate analysis controlling for subject age,
      country of origin, and BE length did not alter these findings. CONCLUSION: The
      reported risk of adenocarcinoma in subjects with BE is low and not significantly
      decreased by a surgical antireflux procedure. Antireflux surgery in the setting
      of BE should not be recommended as an antineoplastic measure.

PMID- 14638339
TI  - High rates of recurrence and of transient reinfections of Helicobacter pylori in
      a population with high prevalence of infection.
AB  - OBJECTIVES: Little is known concerning the magnitude of reinfection versus
      recrudescence of Helicobacter pylori (H. pylori) infection after eradication
      treatment. The aims of this study were to determine the magnitude of H. pylori
      reinfection versus recrudescence, and to identify possible risk factors for
      reinfection. METHODS: Children and adults with upper GI symptoms treated at the
      Centro Medico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, in Mexico
      City, Mexico) were studied. H. pylori infection was diagnosed with urea breath
      test (UBT), histology, and culture. Infected patients received triple therapy,
      and those who became UBT negative 4-6 wk after treatment were considered as
      eradicated and were included in the study. A cohort of 141 patients in whom the
      disease was eradicated was monitored for recurrence with UBT at 3, 6, 9, 12, 18,
      and 24 months. H. pylori was isolated from gastric biopsy samples before
      treatment and at recurrence and isolates compared by genotyping. RESULTS: During
      this period, 32 (22.7%) cases of recurrence were documented the majority
      occurring during yr 1. In nine of the 32 (28.1%) cases, recurrence was eradicated
      spontaneously, suggesting these were transient reinfections. Recurrence rates
      were significantly higher in the subjects 41-60 yr of age than in younger or
      older subjects. H. pylori isolates from 12 recurrence cases were genotyped; nine
      (75%) were classified as true reinfection and three as recrudescence.
      CONCLUSIONS: In our population, recurrence rate is high in adults and transient
      reinfection is common. In several cases, reinfection occurred by multiple
      strains, which suggests that soon after eradication, patients are exposed to
      multiple sources of reinfection.

PMID- 14638340
TI  - Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19
      genotype on the cure rate of 1-week triple therapy for Helicobacter pylori
      infection.
AB  - OBJECTIVES: Genetic polymorphism of interleukin (IL)-1beta is associated with
      differences in gastric acid suppression in response to Helicobacter pylori (H.
      pylori) infection. Thus, the polymorphism might affect H. pylori eradication
      therapy, as antibiotics used in treatment regimens may be acid sensitive. In this
      study, we examined the impact of IL-1beta genetic polymorphism on the cure rate
      of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype
      and antibiotic resistance. METHODS: A total 249 patients with peptic ulcer
      disease were randomized to receive one of the following regimens: amoxicillin and
      clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19
      and IL-1beta-511 genetic polymorphisms were analyzed by polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: The intention-to-treat-based
      overall cure rate was 74.3% (95% CI=68-79%). In the normal acid secretion IL
      1beta genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95%
      CI=56-99%) was significantly higher than among subjects in the CYP2C19 homozygous
      (60.0%, 95% CI=38-78%) and heterozygous (63.6%, 95% CI=46-78%), i.e., extensive
      metabolizer, groups (p<0.05). In the low acid secretion IL-1beta genotype group,
      there was no difference in the cure rate among the CYP2C19 genotype groups.
      Multiple logistic regression analysis identified susceptibility to clarithromycin
      (p<0.0001) and CYP2C19 genotype status (p=0.03) as significant independent
      factors for treatment failure. CONCLUSION: IL-1beta genetic polymorphism,
      although not an independent factor in treatment outcome, influences the impact of
      the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori
      infection.

PMID- 14638341
TI  - Chronic acid-related disorders are common and underinvestigated.
AB  - OBJECTIVES: The aims of this study were as follows: to establish the prevalence
      of chronic acid-related disorders in a managed care population; to describe these
      patients; and to examine rates of adherence to current guidelines for
      investigation of dyspepsia and peptic ulcer disease. METHODS: The design was a
      population-based cohort study. The sample was drawn from 216,720 adult (aged >18
      yr) members of a managed care organization that had an electronic medical record
      linked to administrative and pharmacy databases. We included adults with
      continuous enrollment from July, 1998, to January, 2000, who were dispensed
      histamine-2 blockers or proton-pump inhibitors, or both, for > or =1 yr.
      Dispensing data, sociodemographic and clinical information, comorbidities, and
      investigations were collected and analyzed. RESULTS: The final cohort consisted
      of 5064 patients; 64% were aged > or =50 yr, 47% were male, and 11% were African
      American. The prevalence of chronic acid-related disorders was 2.3%.
      Gastroesophageal reflux disease (59%) was the most common condition, followed by
      dyspepsia (35% of cohort; 18% investigated by endoscopy). There were 917
      dyspepsia patients > or =50 yr who had not been investigated by endoscopy (81% of
      dyspepsia patients in this age group). There were 97 patients with peptic ulcer
      disease who did not have a documented test for Helicobacter pylori (34% of
      patients with peptic ulcer disease). CONCLUSIONS: Chronic acid-related disorders
      are common in primary care, and many patients use acid suppressing medications on
      a long-term basis. Nevertheless, according to current practice guidelines, our
      patients were underinvestigated. Future guidelines should specifically address
      the management of patients who use acid suppressing medications on a chronic
      basis.

PMID- 14638342
TI  - Combination of assay of human telomerase reverse transcriptase mRNA and cytology
      using bile obtained by endoscopic transpapillary catheterization into the
      gallbladder for diagnosis of gallbladder carcinoma.
AB  - OBJECTIVES: It is difficult to make accurate diagnoses of polypoid lesions in the
      gallbladder. To increase the diagnostic accuracy, we have developed an endoscopic
      technique to obtain gallbladder bile, termed endoscopic transpapillary
      catheterization into the gallbladder (ETCG). We evaluated the usefulness of a
      molecular biological approach to the diagnosis of gallbladder carcinoma, in which
      gallbladder bile obtained by the ETCG technique is used. METHODS: Twenty patients
      undergoing an operation because of suspicion of gallbladder carcinoma were
      enrolled. Twelve patients were confirmed to have gallbladder carcinoma, and four
      were found to have chronic cholecystitis. Two patients with polypoid lesion were
      diagnosed as having an inflammatory polyp and a hyperplastic polyp, respectively.
      The remaining two patients with polypoid lesions were diagnosed as having a
      cholesterol polyp. Gallbladder bile collected by the ETCG technique was evaluated
      cytologically and also analyzed for telomerase activity and mRNA for human
      telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. In
      14 patients, hTERT mRNA in resected specimens (fixed in 10% formalin and embedded
      in paraffin) was also examined. RESULTS: Cytology of gallbladder bile was
      positive in eight of 11 examined patients (72.7%) with gallbladder carcinoma.
      hTERT mRNA was detectable in gallbladder bile as well as in resected neoplastic
      tissues in four of 12 patients (33.3%) with carcinoma. Conversely, telomerase
      activity was negative in all eight examined patients with carcinoma. Overall,
      either cytology or hTERT mRNA of gallbladder bile was positive in 10 of 12
      patients (83.3%) with gallbladder carcinoma. Cytology, hTERT mRNA, and telomerase
      activity were negative in eight patients with benign disease. CONCLUSIONS: The
      combination of cytology and hTERT mRNA analysis of gallbladder bile might be
      helpful for the preoperative diagnosis of gallbladder carcinoma.

PMID- 14638343
TI  - Universal precautions guideline: self-reported compliance by gastroenterologists
      and gastrointestinal endoscopy nurses--a decade's lack of progress.
AB  - OBJECTIVES: The aims of this study were to assess and compare the Universal
      Precaution (UP) practices of gastroenterologists (GE) and GI endoscopy nurses
      (GIEN). METHODS: We mailed a 23-item questionnaire to 250 GE and GIEN selected,
      respectively, from the American Board of Internal Medicine online directory and
      the Society of Gastroenterology Nurses and Associates membership directory.
      RESULTS: A total of 77 (31%) GE and 157 (60%) GIEN responded. In all, 32% of GE
      and 50% of GIEN washed their hands before and after handling every patient
      (p<0.01), and 5% of GE and 30% of GIEN wore gloves during all patient contacts
      (p<0.01). Fewer GE than GIEN used face shields for all procedures (14% vs 21%;
      p=0.02). Protective gowns were worn during all procedures by 29% of GE and 46% of
      GIEN (p<0.01). More GE than GIEN either did not recap used needles or used the
      one-handed "scoop" technique (85% vs 77%; p=0.02). When asked to give an overall
      assessment, 46% of GE and 60% of GIEN reported that they always complied with UP
      (p=0.06). Profession, age, gender, hours of daily patient contact, and adequacy
      of staffing did not affect compliance. CONCLUSIONS: GIEN adhered to UP
      recommendations better than GE regarding most items queried except in the
      handling of used needles. Nonetheless, for both groups, compliance with proper
      hand washing and use of gloves, face shields, and gowns was very poor, and
      handling of used needles was satisfactory.

PMID- 14638344
TI  - An assessment of the management of acute bleeding varices: a multicenter
      prospective member-based study.
AB  - OBJECTIVE: Bleeding from esophagogastric varices is a major complication of
      portal hypertension. Despite recent practice guidelines for the management of
      bleeding esophageal or gastric varices, the widespread application of these
      measures by gastroenterologists has not been evaluated. The purpose of this study
      was to continue the concept of membership-based research within diverse practice
      settings by expanding the American College of Gastroenterology (ACG) GI Bleeding
      Registry to assess the management and outcome of acute variceal bleeding.
      METHODS: All ACG members (domestic and foreign) were invited to participate
      during the 1997 Annual Fall meeting and by mail. Data were collected over 12
      months. Information obtained included physician training, practice demographics,
      patient demographics, disease etiology and severity, clinical presentation,
      medications, transfusion needs, therapy, complications, and rebleeding within 2
      wk. RESULTS: A total of 93 physicians/centers (79.6% domestic, 26.9% university
      and affiliated, 3.2% Veterans Affairs) participated. Complete demographic data
      were available for 725 of the 741 patients enrolled with index bleeding. The
      median age of these 725 patients was 52 yr and 73.3% were male. The most common
      single etiology for portal hypertension was cirrhosis (94.3%). The most common
      causes of cirrhosis were alcohol (56.7%), hepatitis C virus (30.3%), and
      hepatitis B virus (10.0%). Hemodynamic instability was noted in 60.7% of the
      patients (22.3% tachycardic, 9.7% orthostatic, 28.7% hypotensive). Index
      interventions included banding (40.8%; median five bands), sclerotherapy (36.3%),
      combination banding/sclerotherapy (6.2%), octreotide (52.6%; median 3 days),
      balloon tamponade (5.5%), transjugular intrahepatic portosystemic shunt (TIPS)
      (6.6%), liver transplantation (1.1%), surgical shunt (0.7%), and embolization
      (0.1%). Transfusion of packed red blood cells, fresh frozen plasma, and platelets
      was given in 83.4%, 44.7%, and 24.6% of the patients with index bleeding,
      respectively. Median transfusion was four units of packed red blood cells, three
      units of fresh frozen plasma, and 1.5 units of platelets. Rebleeding occurred in
      92 of the 741 patients (12.6%) at a median of 7 days (mean 11 days) and was
      treated by banding (18.5%; median six bands), sclerotherapy (30.4%), octreotide
      (63%; median 2 days), balloon tamponade (17.4%), TIPS (15.2%), and surgical shunt
      (3.3%). Complications from the index bleeding and rebleeding within 2 wk included
      ulceration (2.6%, 2.2%), aspiration (2.4%, 3.3%), medication side effects (0.8%,
      0%), dysphagia (2.3%, 0%), odynophagia (2.2%,0%), encephalopathy (13%,17.4%), and
      hepatorenal syndrome (2.4%, 2.2%), respectively. After the index bleeding, 46.2%
      of patients were treated with beta-blockers and 8.2% with nitrates. The majority
      of patients with index bleeding had Child's B cirrhosis (61.5%). Patients
      presenting with recurrent bleeding had mostly Child's B (46.7%) or Child's C
      cirrhosis (44.6%). The overall short-term mortality after index bleeding was
      12.9%. CONCLUSIONS: Acute variceal hemorrhage occurs more often in patients with
      Child's B and C cirrhosis. Endoscopic banding is the most common single
      endoscopic intervention. Adjunctive pharmacotherapy is prevalent acutely and
      after stabilization. Both morbidity and mortality may be lower than reported in
      previous studies.

PMID- 14638345
TI  - Nonfunctioning pancreatic endocrine tumors: a multicenter clinical study.
AB  - OBJECTIVES: Nonfunctioning pancreatic endocrine tumors (NFPTs) are rare neoplasms
      that have been the object of few studies that have involved only small numbers of
      patients. This study was carried out to obtain a comprehensive and up-to-date
      clinical picture of these tumors. METHODS: A total of 184 patients with NFPT
      admitted to three Italian hospitals in the last 15 yr were studied. The diagnosis
      of NFPT was confirmed histologically using conventional and immunohistochemical
      techniques. Data were obtained from the medical charts or directly from the
      patients. RESULTS: There were 85 men (46.2%) and 99 women (53.8%). The mean age
      at diagnosis was 55.2 yr (range 17-82 yr). The percentage of smokers and alcohol
      drinkers was similar to that in the general population. Seven patients (3.9%) had
      a family history of exocrine pancreatic carcinoma. In 120 cases (65.2%), the
      diagnosis was made after workup for pain or other symptoms, in the remaining 64
      cases (34.8%), the tumor was discovered incidentally by ultrasound; in this group
      survival was significantly greater than it was for the symptomatic patients
      (p=0.0043). Survival was also found to be improved by tumor resection (p<0.0001),
      absence of metastases (p<0.0001), and small tumor size (< or =3 cm) (p<0.0007).
      CONCLUSIONS: NFPTs were slightly more frequent in women and were diagnosed most
      often in middle-aged individuals. No risk factors other than a family history of
      exocrine pancreatic carcinoma were found. Tumor discovery while patients were
      still asymptomatic, tumor resection, absence of metastases, and tumor size < or
      =3 cm significantly prolonged survival.

PMID- 14638346
TI  - Nurse-administered propofol versus midazolam and meperidine for upper endoscopy
      in cirrhotic patients.
AB  - OBJECTIVES: Upper GI endoscopy is often performed in patients with chronic liver
      disease to screen for esophageal and gastric varices. Propofol is currently under
      evaluation as an alternative to the combination of midazolam and meperidine for
      sedation during endoscopic procedures. The purpose of this study was to compare
      nurse-administered propofol to midazolam and meperidine for sedation in patients
      with chronic liver disease undergoing diagnostic upper GI endoscopy. METHODS:
      Twenty outpatients who had known chronic liver disease (Child-Pugh class A or B)
      and were undergoing variceal screening were randomized to receive propofol or
      midazolam plus meperidine for sedation. Administration of sedation was performed
      by a registered nurse and supervised by the endoscopist. Outcome measures studied
      were induction and recovery times, efficacy and safety of sedation, patient
      satisfaction, and return to baseline function. RESULTS: The mean dose of propofol
      and meperidine/midazolam administered was 203 mg (SD 43.7, range 150-280) and
      71.3 mg (SD 17.7, range 50-100)/5.3 mg (SD 0.9, range 3.0-6.0), respectively. The
      mean time to achieve adequate sedation was 3.6 min (SD 1.2) for the propofol
      group in comparison to 7.3 min (SD 2.8) for the meperidine/midazolam group
      (p<0.05). Procedure times between the groups were similar: propofol, 3.9 min (SD
      1.9); midazolam/meperidine, 2.7 min (SD 0.8) (p=0.11). The level of sedation
      achieved by the propofol group was greater (p=0.0001). Time to full recovery was
      faster in the propofol group: 34.9 min (SD 10.3) versus 51.6 min (SD 18.4)
      (p<0.05). The mean time to reach a maximal level of alertness on the Observer's
      Assessment of Alertness and Sedation Scale for the propofol group was 15 min (SD
      3.6) versus 29 min (SD 10.5) (p=0.001). Although both groups recorded a high
      level of satisfaction, patients receiving propofol expressed greater overall mean
      satisfaction with the quality of their sedation at the time of discharge
      (p<0.05), and reported a return to baseline function sooner in the majority of
      cases. Propofol achieved comparable levels of efficacy and safety to
      meperidine/midazolam in our study group. Both were well tolerated with minimal
      complications. CONCLUSIONS: Propofol sedation administered by registered nurses
      in the setting of adequate patient monitoring is efficacious and well tolerated
      in patients with liver disease who are undergoing variceal screening by upper
      endoscopy. Patients were more satisfied with the quality of sedation, and return
      to baseline function was usually sooner compared to results achieved with
      midazolam/meperidine. Propofol offers advantages over meperidine/midazolam in
      cirrhotic patients.

PMID- 14638347
TI  - Risk factors for failure of endoscopic stenting of biliary strictures in chronic
      pancreatitis: a prospective follow-up study.
AB  - OBJECTIVES: The aims of this study were to investigate the value of
      interventional endoscopy in patients with strictures of the common bile duct
      (CBD) caused by chronic pancreatitis (CP), and to define the subset of patients
      who may be at risk for failure of endoscopic intervention, in a prospective
      follow-up study. METHODS: A total of 61 patients with symptomatic CBD strictures
      caused by alcoholic CP were treated by endoscopic stent insertion for 1 yr with
      scheduled stent changes every 3 months. After the treatment period, all patients
      entered a follow-up program. RESULTS: Initial endoscopic drainage was successful
      in all cases, with complete resolution of obstructive jaundice. After 1 yr from
      the initial stent insertion, in 19 patients (31.1%) the obstruction was resolved,
      and stents were removed without any need of additional procedures. During a
      median follow-up of 40 months (range 18-66 months), 16 patients had no recurrence
      of symptomatic CBD stricture (long term success rate 26.2%). Of 45 patients who
      needed definitive therapy, 12 patients (19.7%) were treated with repeated plastic
      stent insertion and three (4.9%) with insertion of a metal stent, and 30 patients
      (49.2%) underwent surgery. Among the variables tested, calcification of the
      pancreatic head was the only factor that was found to be of prognostic value. Of
      39 patients with calcification of the pancreatic head, only three (7.7%) were
      successfully treated by a 1-yr period of plastic stent therapy, whereas in 13 of
      22 patients (59.1%) without calcification, this treatment was successful
      (p<0.001). CONCLUSIONS: Endoscopic drainage of biliary obstruction provides
      excellent short term but only moderate long term results. Patients without
      calcifications of the pancreatic head benefit from biliary stenting. Patients
      with calcifications were identified to have a 17-fold (95% CI=4-74) increased
      risk of failure of a 12 month course of endoscopic stenting.

PMID- 14638348
TI  - Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome
      patients with constipation or diarrhea.
AB  - OBJECTIVES: Distinguishing between irritable bowel syndrome (IBS) and functional
      dyspepsia can be challenging because of the variations in symptom patterns, which
      commonly overlap. However, the overlap is poorly quantified, and it is equally
      uncertain whether symptom patterns differ in subgroups of IBS arbitrarily defined
      by primary bowel patterns of constipation (IBS-C) and diarrhea (IBS-D). We aimed
      to determine and to compare the distribution of GI symptoms, both, upper and
      lower, among IBS-C and IBS-D patients. METHODS: A total of 121 consecutive
      patients presenting with a diagnosis of IBS were grouped according to primary
      bowel symptoms as IBS-C (58 women and 18 men, mean age 47 +/- 17 yr) or IBS-D (26
      women and 19 men, mean age 47 +/- 15 yr). The Hopkins Bowel Symptom
      Questionnaire, which includes a brief Quality of Life assessment, and the Hopkins
      Symptom Checklist 90-Revised were completed by all patients at intake. RESULTS:
      IBS-C patients reported significantly more overall GI symptoms when compared to
      patients with IBS-D (6.67 vs 4.62, respectively, p<0.001). Abdominal pain
      patterns differed in patients with IBS-C versus IBS-D (lower abdominal pain:
      40.8% vs 24.4% p=0.05 and upper abdominal pain: 36.8% vs 24.4%, respectively).
      Bloating was substantially more common in IBS-C patients (75%) than in IBS-D
      (40.9%). There were no significant differences in personality subscales by IBS
      subgroup; however, somatization was positively associated with multiple symptom
      reports and was negatively correlated with quality of life. CONCLUSIONS: Upper GI
      symptoms consistent with functional dyspepsia were more frequent in IBS-C.
      Although there was considerable overlap of upper and lower GI symptoms in
      patients with IBS-C and IBS-D, the former had more frequent lower abdominal pain
      and bloating.

PMID- 14638349
TI  - A cost-effectiveness analysis of diagnostic strategies for symptomatic patients
      with ileal pouch-anal anastomosis.
AB  - OBJECTIVE: Pouchitis is often diagnosed based on symptoms and empirically treated
      with antibiotics (treat-first strategy). However, symptom assessment alone is not
      reliable for diagnosis, and an initial evaluation with pouch endoscopy (test
      first strategy) has been shown to be more accurate. Cost-effectiveness of these
      strategies has not been compared. The aim of this study was to compare cost
      effectiveness of different clinical approaches for patients with symptoms
      suggestive of pouchitis. METHODS: Pouchitis was defined as pouchitis disease
      activity index scores > or =7. The frequency of pouchitis in symptomatic patients
      with ileal pouch was estimated to be 51%; the efficacy for initial therapy with
      metronidazole (MTZ) and ciprofloxacin (CIP) was 75% and 85%, respectively. Cost
      estimates were obtained from Medicare reimbursement data. RESULTS: Six competing
      strategies (MTZ trial, CIP trial, MTZ-then-CIP trial, CIP-then-MTZ trial, pouch
      endoscopy with biopsy, and pouch endoscopy without biopsy) were modeled in a
      decision tree. Costs per correct diagnosis with appropriate treatment were $194
      for MTZ trial, $279 for CIP trial, $208 for MTZ-then-CIP trial, $261 for CIP-then
      MTZ trial, $352 for pouch endoscopy with biopsy, and $243 for pouch endoscopy
      without biopsy. Of the two strategies with the lowest cost, the pouch endoscopy
      without biopsy strategy costs $50 more per patient than the MTZ trial strategy
      but results in an additional 15 days for early diagnosis and thus initiation of
      appropriate treatment (incremental cost-effectiveness ratio $3 per additional day
      gained). The results of base-case analysis were robust in sensitivity analyses.
      CONCLUSIONS: Although the MTZ-trial strategy had the lowest cost, the pouch
      endoscopy without biopsy strategy was most cost-effective. Therefore, based on
      its relatively low cost and the avoidance of both diagnostic delay and adverse
      effects associated with unnecessary antibiotics, pouch endoscopy without biopsy
      is the recommended strategy among those tested for the diagnosis of pouchitis.

PMID- 14638350
TI  - Lack of relationship of calcium and vitamin D intake to bone mineral density in
      premenopausal women with inflammatory bowel disease.
AB  - OBJECTIVES: Low bone mineral density has been widely reported in patients with
      inflammatory bowel disease (IBD). The exact etiology of this condition is not
      completely understood but is suggested to be multifactorial, possibly including
      low calcium and vitamin D intake. The objective of this study was to assess
      calcium and vitamin D intake and its relationship to bone mineral density (BMD)
      in premenopausal women with IBD. METHODS: A total of 70 premenopausal women with
      IBD (mean age 33.3 yr, range 18-44 yr) drawn from the population-based University
      of Manitoba IBD Research Registry participated in the study. Calcium and vitamin
      D intake was determined using a semiquantitative food frequency questionnaire and
      compared to the Dietary Reference Intake values for adequacy. BMD of total body,
      lumbar spine, femoral neck, and hip was measured using dual-energy x-ray
      absorptiometry. RESULTS: Of the 70 subjects, 66 successfully completed the study.
      Inadequate calcium intake (<1000 mg/day) was found in 69.7% of the subjects. This
      low intake group had a mean calcium intake of 508 mg/day. Inadequate vitamin D
      intake (<200 IU/day) was found in 53% of the subjects with a mean vitamin D
      intake of 76 IU/day in this group. Calcium and vitamin D intake correlated with
      each other with R2=0.57, p<0.00001. Daily calcium intake was not significantly
      different for subjects with T scores greater than -1 (901 mg) and for subjects
      with T scores less than -1 (875 mg, p=0.44). Daily vitamin D intake was not
      significantly different for subjects with T scores greater than -1 (297 IU)
      compared with subjects with T scores less than -1 was (267 IU, p=0.33). Comparing
      subjects with T scores greater than -1 to those with T score less than -1, there
      was no difference in the percentage of subjects ingesting >1 g/day calcium (14/43
      vs 8/23, p=0.86) or in those with vitamin D intake >200 IU/day (21/43 vs 9/23,
      p=0.45). CONCLUSIONS: The results show that, on average, premenopausal women with
      IBD have less than the recommended intake for calcium and vitamin D. However,
      this does not seem to influence BMD. Calcium and vitamin D intake is not a
      predictor of bone status in premenopausal women with IBD.

PMID- 14638351
TI  - Circulating ghrelin levels in celiac patients.
AB  - OBJECTIVE: Ghrelin, the gut-brain peptide, recently identified as the natural
      endogenous ligand for growth hormone secretagogue receptors, exerts various
      endocrine and nonendocrine effects, including the control of energy homeostasis
      and food intake, but its possible relevance in malabsorption syndromes is
      unknown. Therefore, the aim of this study was to evaluate circulating ghrelin
      levels in adults with untreated and treated celiac disease (CD) and, for
      comparison, in healthy subjects. METHODS: Fasting serum ghrelin levels were
      measured in 30 consecutive patients with newly diagnosed CD, 13 celiac patients
      successfully treated with a gluten-free diet (GFD), and 30 healthy controls.
      RESULTS: Ghrelin levels were abnormally high in patients with active CD compared
      with controls (297 +/- 17.6 vs 218 +/- 15.2 pmol/L, p<0.01) and correlated
      positively with intestinal mucosal lesion severity (rs=0.444, p<0.02). In the
      successfully GFD-treated patients, ghrelin values were normal compared with
      controls (233 +/- 22.0 vs 218 +/- 15.2 pmol/L, ns) and, moreover, correlated
      negatively with body mass index (r=-0.632, p=0.02), unlike in the untreated
      patient group (r=-0.263, ns). CONCLUSION: High ghrelin levels characterized our
      series of adult patients with newly diagnosed CD and correlated significantly
      with the degree of severity of intestinal mucosal lesions. This is the first
      evidence of a relationship between ghrelin and inflammatory processes, but the
      mechanisms involved are still unclear. Furthermore, our findings suggest that an
      interplay of hormonal, metabolic, and nutritional factors could influence ghrelin
      secretion under pathophysiological circumstances.

PMID- 14638352
TI  - NOD2/CARD15 variants are associated with lower weight at diagnosis in children
      with Crohn's disease.
AB  - OBJECTIVES: NOD2/CARD15 variants have recently been shown to be associated with
      Crohn's disease (CD). No analysis of NOD2/CARD15 gene variants has so far been
      reported in pediatric patients. Therefore, our aim was to analyze NOD2/CARD15
      gene variants in children with CD and to perform genotype-phenotype analyses.
      METHODS: We studied 101 children with CD and 136 healthy controls. Detailed
      phenotypic information was obtained from each patient. Patients were genotyped
      for the three NOD2/CARD15 variants R702W (single nucleotide polymorphism 8
      [SNP8]), G908R (SNP12), and L1007fs (SNP13), and genotype-phenotype correlations
      were performed. RESULTS: We found 33 NOD2/CARD15 mutations in 29 of 101 patients
      (29%). The frequency of NOD2 variation was 31% in white (n=87) compared with 11%
      in controls (chi2=14; p=0.0001; OR=3.7; 95% CI=1.7-7.8). Four white patients but
      not control subjects were compound heterozygotes. NOD2/CARD15 variants were
      significantly associated with ileal disease (chi2=4.5; p=0.03; OR=5; 95% CI=0.9
      35.9). Of the children with NOD2/CARD15 variants, 44% were < or =5th percentile
      for weight at diagnosis, whereas only 15% of children without mutations were < or
      =5th percentile (chi2=8.7; p=0.003; OR=4.5; 95% CI=1.4-14.4). Similar trends were
      observed for height but they did not reach statistical significance. CONCLUSIONS:
      Our results demonstrate that: 1) the three NOD2/CARD15 variants confer risk to CD
      in children; 2) NOD2/CARD15 variants are associated with ileal disease in
      children as in adults; and 3) NOD2/CARD15 variants are associated with lower
      weight percentiles at diagnosis in children and a tendency toward lower height
      percentile, suggesting an association between growth in children with CD.

PMID- 14638353
TI  - Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic
      steatohepatitis.
AB  - OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common cause of liver
      disease. Although usually indolent, this disease can progress to cirrhosis in
      some patients. There is currently no proven medical therapy for the treatment of
      NASH. The aim of our study was to evaluate the efficacy of combination alpha
      tocopherol (vitamin E) and vitamin C in reducing histologic inflammation and
      fibrosis. METHODS: This was a prospective, double-blind, randomized, placebo
      controlled trial with a total enrollment of 49 patients; 45 patients completed
      the study. All patients were randomized to receive either vitamins E and C (1000
      IU and 1000 mg, respectively) or placebo daily for 6 months, based on their
      initial histologic diagnosis of NASH. Additionally, all patients were given
      standard weight-loss counseling and encouraged to follow a low fat diet (<30 fat
      g/day). The pre- and posttreatment liver biopsies were reviewed by a single
      pathologist, who was blinded to the patient's medication. Biopsies were scored
      based on a modification of the scoring system published by Brunt et al. (Am J
      Gastroenterol 1999;94:2467-74). A score of 0-4 was possible for fibrosis, and a
      score of 0-6 was possible for inflammation and hepatocyte degeneration and
      necrosis. In addition, body mass index, glycohemoglobin, lipids, and liver
      enzymes were followed throughout the study. RESULTS: Forty-five patients
      completed 6 months of therapy without significant side effects. Vitamin treatment
      resulted in a statistically significant improvement in fibrosis score (p=0.002).
      No changes were noted in inflammation with treatment. Vitamin E and vitamin C, in
      the doses used in this study, were well tolerated and were effective in improving
      fibrosis scores in NASH patients. No improvement in necroinflammatory activity or
      ALT was seen with this combination of drug therapy. A larger, multicenter, longer
      term trial with vitamin E and vitamin C seems to be warranted.

PMID- 14638354
TI  - Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin
      dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon
      alfa.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy of epoetin alfa in
      alleviating anemia and minimizing ribavirin (RBV) dose reductions in patients
      with chronic hepatitis C virus (HCV) infection receiving combination
      RBV/interferon alfa (IFN) therapy. METHODS: HCV-infected patients who had Hb
      levels of 12 g/dl or less during the first 24 wk of combination RBV/IFN therapy
      (n=64) were randomized to treatment with epoetin alfa (40,000 units) s.c. q.w. or
      to standard of care (SOC) for anemia management (RBV dose reduction or
      discontinuation, transfusions). Primary and secondary efficacy endpoints were
      changes in Hb level and RBV dosage, respectively, from baseline to week 16 of
      epoetin alfa therapy. Based on intent-to-treat analysis, the mean changes from
      baseline Hb levels at week 16 were +2.8 g/dl for epoetin alfa versus +0.4 g/dl
      for SOC (p<0.0001), and the mean changes in RBV dosage were -34 mg/day for
      epoetin alfa versus -146 mg/day (p=0.060) for SOC. The mean Hb level at week 16
      in the epoetin alfa group (13.8 g/dl) was significantly (p<0.0001) higher than
      that of the SOC group (11.4 g/dl). At week 4 and subsequently, significantly more
      patients in the epoetin alfa group did not have RBV dosage reductions (p<0.011).
      At study end, 83% of epoetin alfa-treated patients maintained RBV dosages of at
      least 800 mg/day, compared with 54% of patients receiving SOC (p=0.022). Epoetin
      alfa was well tolerated. CONCLUSIONS: In anemic HCV-infected patients treated
      with RBV/IFN, epoetin alfa increases Hb levels and maintains RBV dosing. Based on
      these results, epoetin alfa seems to be promising in the treatment of HCV
      treatment-related anemia. Further research is warranted to determine the
      potential impact on outcomes, including quality of life and sustained viral
      response rate.

PMID- 14638355
TI  - SEN virus infection and the risk of hepatocellular carcinoma: a case-control
      study.
AB  - OBJECTIVE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk
      factors for hepatocellular carcinoma (HCC). The role of a novel DNA virus,
      designated SEN virus (SENV), in the etiology of liver cancer remains to be
      established. The aim of this study was to evaluate the association between SENV
      infection and the risk of HCC by conducting a hospital-based, case-control study
      among Thai patients. METHODS: Eighty-six patients with HCC were enrolled and
      matched individually to a control according to sex, age (+/- 5 yr), and
      geographic background. The presences of HBV DNA, HCV RNA, and SENV DNA in stored
      serum samples were detected with the use of semi-nested polymerase chain reaction
      amplification. RESULTS: Individuals who were infected with SENV did not have
      increased risk of developing HCC (OR=1.49, 95% CI=0.50-4.42). In contrast, those
      who were positive for HBV markers (hepatitis B surface antigen and/or HBV DNA) or
      HCV markers (anti-HCV and/or HCV RNA) had significant risk for HCC (OR=19.91, 95%
      CI=8.26-47.98 and OR=7.97, 95% CI=2.15-29.54, respectively). Moreover,
      coinfection with SENV did not further increase the risk of HCC among patients
      infected with HBV and/or HCV. CONCLUSION: Our data suggest that, unlike chronic
      HBV or HCV infection, SENV infection is not a risk factor for developing HCC in
      Thai populations.

PMID- 14638356
TI  - Treatment of chronic hepatitis B virus infection via oral immune regulation
      toward hepatitis B virus proteins.
AB  - OBJECTIVES: Hepatitis B virus (HBV) is a noncytopathic virus, and hepatocellular
      injury is mediated by a defective host antiviral immune response. We have
      previously shown that antiviral immunity can be modulated through oral feeding of
      viral proteins. The aims of this study were to determine the safety and efficacy
      of treatment of patients with chronic HBV by means of p.o. administration of HBV
      envelope proteins. METHODS: A total of 42 chronic HBV patients were treated p.o.
      with HBV envelope proteins (HBsAg+preS1+preS2), three times/wk for 20-30 wk, and
      followed for an additional 20 wk. Patients were monitored for HBV-DNA levels,
      liver enzymes, and liver histology. HBV-directed T cell immune modulation was
      assessed in vitro by HBV specific T cell-proliferation, cytotoxicity, IFN gamma,
      and IL10 ELISPOT assays, and reverse transcription-polymerase chain reaction
      cytokines assay. RESULTS: Favorable response in one of the primary endpoints was
      achieved in 28/42 patients (66.6%) by means of p.o. immune regulation. A
      significant decrease in viral load was observed in 15 patients (35.7%).
      HBsAg/HBcAg biopsy scores improved in 41% and 57.1% of patients, respectively.
      Histological improvement in liver necroinflammatory score was noted in 12/40
      patients (30%). In all, 80% showed biochemical response. Five of 19 HBeAg
      positive patients (26.3%) became negative for HBeAg. A favorable augmentation in
      anti-HBV specific T cell response, with increased HbsAg specific T cell
      proliferation (78%), cytotoxicity (75%), and IFN gamma positive T cell clones
      (62.9%) was noted. In addition, a decrease in the IL10 gamma positive T cell
      clones was achieved (48.1%). Natural killer T (NKT) lymphocytes increased
      significantly in all treated patients. CONCLUSIONS: Immune regulation of the anti
      HBV immune response via p.o. administration of HBV envelope proteins alleviated
      the immune-mediated liver injury while augmenting the effective antiviral
      immunity.

PMID- 14638357
TI  - Relationship between thrombopoietin serum levels and liver function in patients
      with chronic liver disease related to hepatitis C virus infection.
AB  - OBJECTIVES: Thrombopoietin (Tpo) is an important regulator of megakaryocyte
      maturation and platelet production, and is mainly produced by the liver. A
      decrease in Tpo production is partly responsible for the thrombocytopenia
      observed in patients with chronic liver disease (CLD). The aim of this study was
      to evaluate the relationship between Tpo serum levels and liver function in
      patients with CLD related to hepatitis C virus (HCV) infection. METHODS: We
      studied 37 patients with various degrees of HCV-related CLD. Of the patients, 17
      had chronic hepatitis and 20 liver cirrhosis. Liver function was evaluated in all
      patients by the following hepatic blood flow dependent and independent tests that
      explore various hepatic metabolic functions: carbon-13 (13C)-aminopyrine breath
      test (13C-ABT), 13C-galactose breath test (13C-GBT), and monoethylglycinexylidide
      (MEGX) test. Liver function tests results were correlated with Tpo serum levels.
      RESULTS: Tpo serum levels were significantly lower in patients with liver
      cirrhosis (88 +/- 23 pg/ml) as compared to those in patients with chronic
      hepatitis (128 +/- 55 pg/ml, p=0.0031). However, they did not correlate with
      serum albumin, bilirubin, or prothrombin activity. Tpo serum levels showed a
      significant positive correlation with 13C-ABT results (hourly dose at 30 min,
      rs=0.489, p=0.002; cumulative dose at 120 min, rs=0.425, p=0.008). Moreover, they
      showed a fair, positive correlation with 13C-GBT hourly dose at 30 min (rs=0.366,
      p=0.028), and a trend toward a positive correlation with the various MEGX test
      sampling times (MEGX15, rs=0.314, p=0.059; MEGX30, rs=0.284, p=0.088; and MEGX60,
      rs=0.320, p=0.059). CONCLUSIONS: In this study we have shown that a progressive
      decline in liver function in patients with HCV-related CLD is paralleled by a
      decrease in Tpo production. The different correlations observed between Tpo and
      the various liver function tests suggests that this finding is mainly the result
      of a decrease in hepatic functional mass rather than dependent on alteration in
      splanchnic hemodynamic.

PMID- 14638358
TI  - Transjugular intrahepatic portosystemic shunt for refractory ascites: an analysis
      of the literature on efficacy, morbidity, and mortality.
AB  - OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is frequently
      used to treat patients with refractory ascites, but its role is controversial. We
      sought to determine from the literature the efficacy, morbidity, and mortality
      associated with TIPS for refractory ascites. METHODS: We searched MEDLINE and
      identified studies published in English from January, 1985, to March, 2003, that
      evaluated the effect of TIPS in patients with refractory ascites. Outcomes that
      were analyzed included complete resolution of ascites, reduction in ascites,
      mortality, encephalopathy, stenosis, and renal function. Data were analyzed on an
      intention to treat basis. RESULTS: Of 25 studies identified, 16 were included in
      the analysis. The pooled estimate for complete response at 6 months was 45% and
      for any response (complete and partial) was 63%. Pooled 6-month mortality after
      TIPS was 36%. Risk factors for mortality included renal insufficiency (serum
      creatinine >1.5 mg/dl), hyperbilirubinemia (total bilirubin >3 mg/dl), advanced
      age (>60 yr), and poor response to TIPS. The pooled rate of new or worsening
      encephalopathy after TIPS was 32%. In most cases, encephalopathy was managed
      medically or by reduction in shunt size; however, refractory cases were
      associated with 100% mortality in most studies. Studies reporting the effect of
      TIPS on kidney function showed improvement in creatinine clearance and urinary
      sodium excretion. CONCLUSIONS: TIPS is effective in eliminating ascites or
      substantially reducing ascites in cases refractory to medical therapy. Renal
      insufficiency, refractory encephalopathy, and hyperbilirubinemia were
      consistently associated with mortality after TIPS. In individuals with risk
      factors for mortality, alternative strategies should be recommended.

PMID- 14638359
TI  - Protein kinase R is increased and is functional in hepatitis C virus-related
      hepatocellular carcinoma.
AB  - OBJECTIVE: Protein kinase R (PKR) interacts with dsRNA and phosphorylates
      eukaryotic initiation factor-2 (eIF2alpha), which in turn inhibits host
      translation initiation as well as hepatitis C virus (HCV) translation. Because
      PKR inhibits host cell growth and proliferation, it has also been proposed to act
      as a eukaryotic tumor suppressor. To evaluate the role of PKR in HCV-related
      hepatocellular carcinoma (HCC), we compared PKR and related protein expression in
      paired tumor (T) and surrounding nontumor (NT) tissue. METHODS: Tissue samples
      were obtained from 12 HCV-infected HCCs. To determine PKR and related protein
      expression, Western blotting and semiquantitative reverse transcriptase
      polymerase chain reaction were performed. RESULTS: PKR protein levels were
      consistently increased in HCV-related HCC compared with NT (p=0.001); similar
      increases were seen in total eIF2alpha and the PKR inhibitor p58IPK in T compared
      with NT (p=0.022, p=0.048, respectively). Relative increases in phosphorylated
      eIF2alpha (peIF2alpha) were also seen, and the ratio of peIF2alpha/total
      eIF2alpha did not change in T compared with NT, suggesting that PKR remains
      functional within T. Cytoplasmic levels of HCV RNA within T were decreased
      compared with NT. CONCLUSIONS: These findings indicate that PKR has increased
      activity in human HCC compared with LC, and suggest that PKR acts as a growth
      inducer in HCC.

PMID- 14638360
TI  - The risk of end stage liver disease and hepatocellular carcinoma among persons
      infected with hepatitis C virus: publication bias?
AB  - OBJECTIVES: In persons infected with hepatitis C virus (HCV), the incidence of
      cirrhosis and hepatocellular carcinoma (HCC) can be estimated by examining over
      time entire cohorts with known onset of HCV infection. We performed a systematic
      review of the literature to identify and to analyze studies that examine such
      cohorts. METHODS: A search of all articles from 1980 to 2001 was performed.
      Published studies were included in which chronic HCV infection was defined by
      elevation of liver enzymes or persistent RNA. We excluded studies in which
      cohorts were selected from patients with prevalent liver disease or in whom the
      onset of infection could not be estimated. Two investigators abstracted the data.
      The incidences of cirrhosis and HCC were analyzed in all studies and in
      categories based on study design, mode of HCV acquisition, sample size and
      duration of follow-up, age at the onset of infection, and the quality of
      estimating the onset of HCV infection. RESULTS: Of the articles, 21 fulfilled the
      selection criteria. Studies varied in sample size (17-1,680), duration of follow
      up (8-45 yr), total person-years (157-34,098), and the mean age at onset of HCV
      (5-58 yr). The mean time to end stage liver disease (ESLD) was 4-23 yr and to HCC
      was 9-31 yr. A funnel plot showed a possible publication bias against studies
      with low incidence of ESLD and HCC. The pooled weighted incidence rates for ESLD
      and HCC based on infection mode were as follows: community-acquired HCV, 1.9 and
      0 per 1,000 person-years; transfusion associated, 4.5 and 0.7; hemophilia
      patients, 7.9 and 1.0; anti-D IgG, 0.7 and 0 per 1,000 person-years. Poisson
      regression modeling showed that the incidence of ESLD is increased in studies
      with a low quality estimate of the onset of HCV infection, in community-acquired
      and transfusion-associated HCV, and in studies with prospective design.
      CONCLUSIONS: We found large variation in the incidence estimates of cirrhosis and
      HCC. Short duration of follow-up, small sample size, and possible publication
      bias may explain some of this variation. Low quality estimates of the onset of
      HCV infection, a prospective study design, and a transfusion- or hemophilia
      related mode of acquisition were independent predictors of high reported
      incidence of ESLD.

PMID- 14638361
TI  - A prospective clinicopathological and endoscopic evaluation of flat and depressed
      colorectal lesions in the United Kingdom.
AB  - OBJECTIVES: Flat and depressed colorectal lesions are now reported in Western
      populations. The malignant potential, anatomical distribution, and other
      clinicopathological features have not been established in this group. This study
      aimed to assess prospectively the prevalence, clinicopathological, and endoscopic
      features of flat and depressed colorectal lesions in the United Kingdom. METHODS:
      A single endoscopist performed colonoscopy on 850 consecutive patients presenting
      for routine colonoscopy. All endoscopies were performed using a high
      magnification colonoscope with chromoscopy to facilitate detection of flat and
      depressed colorectal lesions. RESULTS: A total of 458 flat lesions were
      identified. Of these, 173 (38%) were hyperplastic and 285 (62%) adenomatous or
      beyond. Of the 173 hyperplastic flat lesions, 162 (94%) were located in the recto
      sigmoid region. Of the 267 adenomas, 66 (25%) had areas of high grade dysplasia
      (HGD), with 54/66 (82%) being present in the right colon. Flat lesions <8 mm in
      diameter was more likely to contain HGD than those <8 mm (p<0.001). Nine of the
      10 (90%) flat invasive adenoacarcinomas were in the right colon and all had a
      depressed morphological component. In contrast, HGD was observed in 58/466 (12%)
      of protuberant (sessile/pedunculated) adenomas of which 95% (55/58) were located
      in the left colon. In addition, HGD was present in 17% of all sessile adenomas
      versus 44.6% of flat lesions >8 mm in diameter (p=0.001). Of the 14 protuberant
      carcinomas, 13/14 (93%) were in the left colon. Synchronous lesions were found in
      96/816 (12%) of cases. Of the 816 patients with two or more left-sided
      protuberant adenomas <8 mm (with or without HGD), 89 (11%) had one or more flat
      lesions in the right colon with HGD. CONCLUSIONS: Flat adenomas and carcinomas
      have a high malignant potential compared to protuberant lesions and have a
      propensity for developing in the right hemi-colon. Total colonoscopy is required
      to detect such lesions, as only 18% of flat lesions would be in reach of the
      flexible sigmoidoscope.

PMID- 14638362
TI  - Testing of multiple samples increases the sensitivity of stool decay-accelerating
      factor test for the detection of colorectal cancer.
AB  - OBJECTIVES: We previously reported that the measurements of stool decay
      accelerating factor (DAF), a membrane-bound, complement regulatory protein, may
      be valuable for the detection of colorectal cancer. Recently we have refined the
      immunoassay for stool DAF. In the present study, using the refined assay, we
      measured stool DAF concentrations in multiple samples from patients with
      colorectal cancer and in healthy controls to determine whether testing of
      multiple samples would increase the sensitivity of the stool DAF test. METHODS:
      DAF was measured in three spontaneously passed stool samples from each of 100
      patients with colorectal cancer and 100 control subjects without apparent
      colorectal disease. RESULTS: The stool DAF concentrations in the patients with
      colorectal cancer (median 11.1 ng/g stool; interquartile range 2.9-32.7 ng/g)
      were significantly higher than concentrations in the subjects without colorectal
      diseases (median 1.6 ng/g stool; interquartile range 0.4-3.4 ng/g) (p<0.0001).
      Testing of two samples from each patient significantly increased the sensitivity
      (72%) of the stool DAF test without significantly decreasing its specificity
      (92%). The stool DAF test was positive in more than one half of patients with
      colorectal cancer at a relatively early TNM stage or with negative fecal occult
      blood test. CONCLUSIONS: These findings suggest that stool DAF is a marker of
      colorectal cancer independent of fecal occult blood and testing of two samples
      increases the sensitivity of the stool DAF test. Measurement of stool DAF now
      seems worthy of further consideration as a noninvasive method for the detection
      of colorectal cancer.

PMID- 14638363
TI  - Familial visceral myopathy with pseudo-obstruction, megaduodenum, Barrett's
      esophagus, and cardiac abnormalities.
AB  - This report describes a new subgroup of familial visceral myopathy. Three
      patients from within this family were admitted to the hospital with pseudo
      obstruction. Barium x-ray, abdominal plain film, esophageal manometry,
      colonoscopy, gastroscopy, and echocardiography were performed in all siblings for
      diagnostic evaluation. Two of our patients had surgery because of suspicion of
      acute abdomen. In one of them, full-thickness biopsy, which was performed during
      laparotomy, revealed findings that were compatible with familial visceral
      myopathy. Three siblings from this family with visceral myopathy, in which the
      parents were consanguineous, had megaduodenum, long-segment Barrett's esophagus,
      and different cardiac abnormalities.

PMID- 14638364
TI  - Barium evaluation of esophageal strictures: still useful or a bust?

PMID- 14638365
TI  - Percutaneous radio-frequency liver tumor ablation: what are the risks?

PMID- 14638366
TI  - Should enteral feeding be the standard of care for acute pancreatitis?

PMID- 14638367
TI  - Prevalence and incidence of cryoglobulins in chronic hepatitis C patients.

PMID- 14638369
TI  - Helicobacter pylori infection in patients with inflammatory bowel disease.

PMID- 14638371
TI  - Small intestinal bacterial overgrowth and irritable bowel syndrome.

PMID- 14638373
TI  - High prevalence of celiac disease in psoriasis.

PMID- 14638374
TI  - Small-diameter endoscope enabled endoscopist to detect his own duodenal erosion.

PMID- 14638375
TI  - Acute leukemia after infliximab therapy.

PMID- 14638376
TI  - Enterra for gastroparesis.

PMID- 14638377
TI  - Raynaud's phenomenon and celiac disease.

PMID- 14638378
TI  - Oropharyngeal varix presenting with melena.

PMID- 14638379
TI  - An unusual complication of a nonendoscopically placed PEG tube.

PMID- 14638380
TI  - Megaesophagus after fundoplication.

PMID- 14638381
TI  - Gender-specific effect of maternal deprivation on anxiety and corticotropin
      releasing hormone mRNA expression in rats.
AB  - The long-term behavioral and neurochemical effects of 24h maternal separation
      were assessed in rats of both genders. Maternal deprivation was applied at the
      age of 9 days, whereas consequences were assessed 3 months later. Deprived rats
      (irrespective of gender) showed a considerable growth retardation that
      disappeared till adulthood. The plus-maze performance of control and deprived
      males did not differ under normal conditions, but deprived males showed more
      anxiety when the test was applied shortly after stress exposure. CRH mRNA
      expression in the amygdala, but not in the hypothalamus, was more intense in
      deprived as compared with control males. Deprived females were not affected.
      These data suggest that (i) the maternal deprivation induced changes are larger
      in males than in females, (ii) maternal deprivation induces a latent behavioral
      disposition towards anxiety that is precipitated by acute stressors, and (iii)
      the changes noticed in amygdalar CRH expression may serve as mechanisms for the
      behavioral changes noticed.

PMID- 14638382
TI  - Effect of haloperidol and risperidone on amyloid precursor protein levels in
      vivo.
AB  - The neurotoxic beta-amyloid peptide of Alzheimer's disease is formed from the
      amyloid precursor protein (APP), which is a member of an evolutionarily highly
      conserved gene family with significant functional importance. Because behavioral
      and psychiatric symptoms treated with antipsychotics may influence the course of
      the disease, we have investigated traditional and atypical antipsychotic drugs,
      administered through the intraperitoneal route, for their effects on rat cortical
      APP. Western-immunoblotting was utilized for semi-quantitative evaluation of APP
      levels. Treatment with haloperidol resulted in an acute elevation of cortical APP
      both in therapeutic and toxic doses, however, it had no significant chronic
      impact on APP. Atypical antipsychotic risperidone did not change cortical APP
      concentration. These results indicate that both haloperidol and risperidone are
      considered to be relatively safe with respect to APP metabolism. Possible
      mechanisms, including involvement of calcium and APP itself as a receptor, are
      discussed.

PMID- 14638383
TI  - Hydrogen peroxide induces apoptosis in cerebral vascular smooth muscle cells:
      possible relation to neurodegenerative diseases and strokes.
AB  - Recently, reactive oxygen species (ROS) have been suggested as important
      mediators of brain damage in a number of disease states, including traumatic
      brain injury, neurodegenerative diseases and strokes. Apoptosis has been
      suggested to play an important role in neurodegenerative diseases, traumatic
      brain injury and strokes. The aim of this study was to determine whether or not
      cerebral vascular smooth muscle cells (CVSMCs) undergo apoptosis following
      treatment with hydrogen peroxide (H2O2). Herein, we demonstrate, for the first
      time, that H2O2 can induce apoptosis in a concentration-dependent manner in
      primary cultured CVSMCs, as measured by several morphological and biochemical
      criteria. H2O2-induced apoptosis may be initiated by stimulating Ca2+-dependent
      endonuclease activity. The present new data suggest that apoptosis in cerebral
      VSMCs, induced by ROS, such as H2O2, could play important roles in
      neruodegenerative processes, traumatic brain injury and strokes.

PMID- 14638384
TI  - Effects of electrolytic and 6-hydroxydopamine lesions of rat nigrostriatal
      pathway on nitric oxide synthase and nicotinamide adenine dinucleotide phosphate
      diaphorase.
AB  - The aim of the present study was to assess degenerative changes in the nitric
      oxide (NO) system of basal ganglia in animals with experimentally induced
      Parkinson's disease. In one procedure, rats were stereotaxically injected with 6
      hydroxydopamine (6-OHDA) in the right medial forebrain bundle; in a second
      procedure, electrodes were implanted in the right substantia nigra pars compacta
      (SNc). After 15 and 30 days animals were tested for rotational asymmetry induced
      by apomorphine. Apomorphine induced rotation in lesioned animals, towards the
      ipsilateral side after electrolytic lesion and towards contralateral side in 6
      OHDA animals. Structural deficits in basal ganglia were quantified by
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry
      and by nitric oxide synthase (NOS) immunoreactivity. 6-OHDA and electrolytic
      lesions induced a significant decrease in the number of NADPH-d/NOS positive
      cells in the lesion ipsilateral to SNc, in contrast with cell number increase in
      the ipsilateral dorsal striatum. By contrast, 6-OHDA-treated animals showed a
      decrease in the number of NOS immunoreactive cells in the contralateral nucleus
      accumbens. We conclude that populations of NO-synthesizing neurons are
      differentially regulated in Parkinson's disease induced by different experimental
      procedures.

PMID- 14638385
TI  - Effects of excitotoxic lesions of the gustatory thalamus on latent inhibition and
      blocking of conditioned taste aversion in rats.
AB  - The influence of bilateral excitotoxic lesions of the gustatory thalamus on
      latent inhibition and blocking of conditioned taste aversion (CTA) was examined
      in two experiments. In Experiment 1, rats with thalamic lesions showed normal
      latent inhibition by acquiring a CTA that was significantly weaker when the
      conditioned stimulus (CS) was familiar than when it was novel. In Experiment 2,
      the preconditioned element (sodium chloride) of a compound CS blocked the
      acquisition of a CTA to the novel element (sucrose) in normal rats. Irrespective
      of whether sodium chloride was preconditioned or not, rats with thalamic lesions
      showed little or no aversion to sucrose following compound conditioning. Overall,
      the results provide no support for the experimental hypothesis that thalamic
      lesions disrupt decremental changes in the attentional processing of gustatory
      stimuli.

PMID- 14638386
TI  - 3,4-DAP-evoked transmitter release in hippocampal slices of aged rats with
      impaired memory.
AB  - Based on a slice superfusion technique, this study investigated the release of
      acetylcholine, noradrenaline and serotonin in the hippocampus of aged rats (25-27
      months) showing no or severe deficits in a spatial reference-memory task (water
      maze). Young adults (3-5 months) were used as controls. 3,4-diaminopyridine (3,4
      DAP), a potassium channel antagonist which increases neuronal excitability, was
      used to evoke the overflow of the three neurotransmitters. The release of
      [3H]noradrenaline induced by stimulation of presynaptic nicotinic receptors was
      also assessed. The experiment compared the accumulation and 3,4-DAP-evoked (or
      nicotine-evoked) overflow of [3H] in hippocampal slices preincubated with
      [3H]choline, [3H]noradrenaline, or [3H]serotonin. In aged rats, only the
      accumulation of [3H]serotonin was reduced significantly (-17%). In percent of
      tissue-[3H], the 3,4-DAP-evoked overflow of [3H]serotonin was increased (+28%),
      and that of [3H]acetylcholine was reduced (-23%) in the aged rats. The nicotine
      evoked overflow of [3H]noradrenaline was not altered in aged rats. There was a
      significant correlation of water-maze performance (distance to platform) and
      evoked overflow of [3H]serotonin. It is concluded that hippocampal cholinergic
      functions are more altered by aging than noradrenergic or serotonergic ones.
      Excessive excitability of serotonergic terminals, perhaps in addition to
      cholinergic dysfunction, might be a crucial factor accounting for age-related
      cognitive deficits in the present population of rats.

PMID- 14638388
TI  - Sleep and synaptic homeostasis: a hypothesis.
AB  - During much of sleep, the cerebral cortex is rippled by slow waves, which appear
      in the electroencephalogram as oscillations between 0.5 and 4.5 Hz. Slow waves
      are regulated as a function of previous wakefulness, being maximal at the
      beginning of sleep and then progressively returning to a baseline level. This
      paper discusses a hypothesis about the significance of slow-wave activity and its
      homeostatic regulation. The hypothesis is as follows: 1. Wakefulness is
      associated with synaptic potentiation in several cortical circuits; 2. Synaptic
      potentiation is tied to the homeostatic regulation of slow-wave activity; 3. Slow
      wave activity is associated with synaptic downscaling; 4. Synaptic downscaling is
      tied to the beneficial effects of sleep on performance. The hypothesized link
      between sleep and synaptic homeostasis is supported by several lines of evidence
      and leads to testable predictions.

PMID- 14638387
TI  - Caudate volume as an outcome measure in clinical trials for Huntington's disease:
      a pilot study.
AB  - Previous research has demonstrated that longitudinal change in caudate volume
      could be observed over a period of 3 years in subjects with Huntington's disease
      (HD). The current pilot study was designed to determine whether measurement of
      caudate change on magnetic resonance imaging (MRI) is a feasible and valid
      outcome measure in an actual clinical trial situation. We measured caudate
      volumes on pre- and post-treatment MRI scans from 19 patients at two sites who
      were participating in CARE-HD (Co-enzyme Q10 and Remacemide: Evaluation in
      Huntington's Disease), a 30-month clinical trial of remacemide and co-enzyme
      Q(10) in symptomatic patients with HD. Results from this pilot study indicated
      that decrease in caudate volume was significant over time. Power analysis
      indicated that relatively small numbers of subjects would be needed in clinical
      trials using caudate volume as an outcome measure. Advantages and disadvantages
      of using MRI caudate volume as an outcome measure are presented. We recommend the
      adoption of quantitative neuroimaging of caudate volume as an outcome measure in
      future clinical trials for treatments of HD.

PMID- 14638389
TI  - The effect of nitric oxide synthase inhibition on cognitive ability and
      strategies employed for place learning in the water maze: sex differences.
AB  - Male and female rats use different cognitive strategies in the solution of place
      learning problems in the water maze despite similar abilities. The female-type
      strategy has been negatively correlated with cortical nitric oxide (NO)
      metabolites. The present study aimed to examine the effect of NO synthase (NOS)
      inhibition (N(omega)-nitro-L-arginine, L-NA) on cognitive ability and strategy in
      the water maze, and to evaluate possible sex differences. In a 2 (male versus
      female) x2 (L-NA versus saline) factorial design, rats were trained to find the
      platform (visible or hidden), always in the same position, for 12 days. L-NA
      impaired acquisition, during the earlier phases and more prominently in females.
      This impairment was quite dramatic and unique to females during the first day
      that the platform was hidden following 3 days of visible-platform conditions.
      After acquisition, the visible platform's position was shifted, thereby
      presenting the rats with a choice (searching for the hidden platform in the
      previous location, i.e. adopting a conceptual cognitive style, or escaping to the
      visible platform in a new position, i.e. adopting a perceptual style). On the
      first of the four shift trials (where the newly positioned platform was proximal
      to the rat's starting position), female rats showed the previously found tendency
      to adopt a perceptual style escape directly in clear contrast to saline-treated
      males. The L-NA-treated males tended to manifest female-like perceptual style,
      suggesting that inhibition of NO synthesis in males weakened the tendency to
      choose a conceptual style in this shifted-platform task. The role of NO in both
      cognitive and non-cognitive psychological functions is discussed.

PMID- 14638390
TI  - Enhancement of electroacupuncture-induced analgesic effect in cholecystokinin-A
      receptor deficient rats.
AB  - Previously, we have showed that the cholecystokinin (CCK)-A receptor expression
      in hypothalamus is closely related with the responsiveness of electroacupuncture
      (EA)-mediated analgesic effects in rats. In order to confirm this observation
      more directly in vivo, the EA-mediated analgesic effects are compared between
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats, the natural knockout rats with
      the homozygously disrupted CCK-A receptor gene, with Long-Evans Tokushima Otsuka
      (LETO) rats. They were stimulated at the zusanli (ST36) acupoint without using
      anesthetics or holders. The tail flick latency (TFL) test was performed to
      quantify analgesic effects and then the mean TFL increase ratios were calculated.
      OLETF rats showed a mean increase of 53% and LETO rats showed a mean increase of
      31% of TFL. Our results suggest that the analgesic effect of acupuncture is
      closely related with the amount of CCK-A receptor expression.

PMID- 14638391
TI  - TSII toxin isolated from Tityus serrulatus scorpion venom: behavioral,
      electroencephalographic, and histopathologic studies.
AB  - We have reported earlier that intrahippocampal administration of the C-pool from
      Tityus serrulatus scorpion venom induces convulsions in rats. Here we report the
      effects of seven toxins isolated from the C-pool. The strongest effects were seen
      after toxin 5C, which was sequenced and identified as TSII, a beta-type toxin
      that affects Na+ channel activation. Unilateral injection of TSII in the rat
      hippocampus (1.7 microg/microl) induced clusters of spikes and epileptic
      discharges of mainly moderate intensity, convulsion-related behavioral changes
      (wet dog shakes, staring, masticatory jaw movements, facial automatisms,
      orofacial movements, intense sniffing, blinking, and forelimb clonus with rearing
      and falling) and a massive neuronal loss of pyramidal cells in the ipsilateral
      CA1, CA3, and CA4 subfields and of granulate cells of the ipsilateral dentate
      gyrus. Toxins C3, C4, and C6 induced weaker changes in the EEG and behavioral
      changes and failed to induce cell death, and toxins C1, C2, and C7 had no
      effects. The similarities in the effects of TsTx, a alpha-type toxin that affects
      Na+ channel, suggest that the loss of modulation of activation of the sodium
      channel caused by TSII increases glutamate release, leading to long-lasting
      increases in intracellular Ca2+ and cell death.

PMID- 14638392
TI  - Vaccines and animal models for arboviral encephalitides.
AB  - Arthropod-borne viruses ("arboviruses") cause significant human illness ranging
      from mild, asymptomatic infection to fatal encephalitis or hemorrhagic fever. The
      most significant arboviruses causing human illness belong to genera in three
      viral families, Togaviridae, Flaviviridae, and Bunyaviridae. These viruses
      represent a significant public health threat to many parts of the world, and, as
      evidenced by the recent introduction of the West Nile virus (WNV) to the Western
      Hemisphere, they can no longer be considered specific to any one country or
      region of the world. Like most viral diseases, there are no specific therapies
      for the arboviral encephalitides; therefore, effective vaccines remain the front
      line of defense for these diseases. With this in mind, the development of new,
      more effective vaccines and the appropriate animal models in which to test them
      become paramount. In fact, for many important arboviruses (e.g. California
      serogroup and St. Louis encephalitis viruses), there are currently no approved
      vaccines available for human use. For others, such as the alphaviruses, human
      vaccines are available only as Investigational New Drugs, and thus are not in
      widespread use. On the other hand, safe and effective vaccines against tick-borne
      encephalitis virus (TBEV) and Japanese encephalitis virus (JEV) have been in use
      for decades. New challenges in vaccine development have been met with new
      technologies in vaccine research. Many of the newer vaccines are now being
      developed by recombinant DNA technology. For example, chimeric virus vaccines
      have been developed using infectious clone technology for many of the arboviruses
      including, WNV, JEV, and TBEV. Other successful approaches have involved the use
      of naked DNA encoding and subsequently expressing the desired protective
      epitopes. Naked DNA vaccines have been used for TBEV and JEV and are currently
      under development for use against WNV. The development of less expensive, more
      authentic animal models to evaluate new vaccines against arboviral diseases will
      become increasingly important as these new approaches in vaccine research are
      realized. This article reviews the current status of vaccines, both approved for
      use and those in developmental stages, against the major arboviral encephalitides
      causing human disease. In addition, research on animal models, both past and
      present, for these diseases are discussed.

PMID- 14638393
TI  - Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1
      infection in vitro and in vivo.
AB  - Twenty Thai medicinal plant extracts were evaluated for anti-herpes simplex virus
      type 1 (HSV-1) activity. Eleven of them inhibited plaque formation of HSV-1 more
      than 50% at 100microg/ml in a plaque reduction assay. Aglaia odorata, Moringa
      oleifera, and Ventilago denticulata among the 11 were also effective against
      thymidine kinase-deficient HSV-1 and phosphonoacetate-resistant HSV-1 strains.
      These therapeutic efficacies were characterized using a cutaneous HSV-1 infection
      in mice. The extract of M. oleifera at a dose of 750mg/kg per day significantly
      delayed the development of skin lesions, prolonged the mean survival times and
      reduced the mortality of HSV-1 infected mice as compared with 2% DMSO in
      distilled water (P<0.05). The extracts of A. odorata and V. denticulata were also
      significantly effective in limiting the development of skin lesions (P<0.05).
      There were no significant difference between acyclovir and these three plant
      extracts in the delay of the development of skin lesions and no significant
      difference between acyclovir and M. oleifera in mean survival times. Toxicity of
      these plant extracts were not observed in treated mice. Thus, these three plant
      extracts may be possible candidates of anti-HSV-1 agents.

PMID- 14638394
TI  - Structure-activity relationship of neomycin, paromomycin, and neamine-arginine
      conjugates, targeting HIV-1 gp120-CXCR4 binding step.
AB  - We have recently designed and synthesized aminoglycoside-arginine conjugates
      (AACs) as potential anti-HIV-1 agents. AACs exert a number of activities related
      to Tat antagonism. We here present a new set of AACs, conjugates of neomycin B,
      paromomycin, and neamine with different number of arginines (1-6), their (a)
      uptake by human T-cell lines, (b) antiviral activities, (c) competition with
      monoclonal antibody (mAb) 12G5 binding to CXCR4, (d) competition with stromal
      cell-derived factor-1 (SDF-1alpha) binding to CXCR4, and (e) competition with HIV
      1 coat protein gp120 cell penetration. The appearance of mutations in HIV-1 gp120
      gene in AACs resistant HIV-1 isolates, supports that AACs inhibit HIV-1
      infectivity via interference of gp120-CXCR4 interaction. Our results point that
      the most potent AACs is the hexa-arginine-neomycin conjugate, the other multi
      arginine-aminoglycoside conjugates are less active, and the mono-arginine
      conjugates display the lowest activity. Our studies demonstrate that, in addition
      to the core, the number of arginines attached to a specific aminoglycoside, are
      also important in the design of potent anti-HIV agents. The AACs play an
      important role, not only as HIV-1 RNA binders but also as inhibitors of viral
      entry into human cells.

PMID- 14638395
TI  - Antiviral activity of lactoferrin against canine herpesvirus.
AB  - Lactoferrin (LF) is an iron-binding protein that is found in milk and other
      mammalian secretions. We found that bovine lactoferrin (bLF) inhibited both the
      in vitro infection and replication of canine herpesvirus (CHV) in Madin-Darby
      canine kidney (MDCK) cells. Incubation of CHV with bLF prevented subsequent
      infection of MDCK cells. Furthermore, proteins from CHV-infected MDCK cells were
      resolved by SDS-PAGE, and then bLF CHV-binding proteins were identified by far
      Western blotting. We demonstrated that the anti-CHV activity of bLF was due to
      its interaction with CHV as well as with MDCK cells. Both the apo- and holo-forms
      of bLF inhibited virus multiplication independently of their iron-withholding
      properties. We also demonstrated that human LF had anti-CHV activity. Our
      findings suggest that LF could be effective in dogs to provide protection against
      CHV infection.

PMID- 14638396
TI  - In vitro and in vivo antiviral properties of sulfated galactomannans against
      yellow fever virus (BeH111 strain) and dengue 1 virus (Hawaii strain).
AB  - Two galactomannans, one extracted from seeds of Mimosa scabrella, having a
      mannose to galactose ratio of 1.1, and another with a 1.4 ratio from seeds of
      Leucaena leucocephala, were sulfated. The products from M. scabrella (BRS) and L.
      leucocephala (LLS) had a degree of sulfation of 0.62 and 0.50, and an average
      molecular weight of 620x10(3) and 574x10(3) gmol(-1), respectively. Their
      activities against yellow fever virus (YFV; BeH111 strain) and dengue 1 virus
      (DEN-1; Hawaii strain) were evaluated. This was carried out in young mice
      following intraperitoneal infection with YFV. At a dose of 49 mgkg(-1), BRS and
      LLS gave protection against death in 87.7 and 96.5% of the mice, respectively.
      When challenged with 37.5 LD50 of YFV, mice previously inoculated with BRS+virus
      or LLS+virus, showed 93.3 and 100% resistance, respectively, with neutralization
      titers similar to mice injected with 25 LD50 of formaldehyde-inactivated YFV. In
      vitro experiments with YFV and DEN-1 in C6/36 cell culture assays in 24-well
      microplates showed that concentrations that produced a 100-fold decrease in virus
      titer of YFV were 586 and 385 mgl(-1) for BRS and LLS, respectively. For DEN-1
      they were 347 and 37 mgl(-1), respectively. Sulfated galactomannans, thus
      demonstrate in vitro and in vivo activity against flaviviruses.

PMID- 14638397
TI  - Substituted benzimidazoles with nanomolar activity against respiratory syncytial
      virus.
AB  - A cell-based assay was used to discover compounds inhibiting respiratory
      syncytial virus (RSV)-induced fusion in HeLa/M cells. A lead compound was
      identified and subsequent synthesis of >300 analogues led to the identification
      of JNJ 2408068 (R170591), a low molecular weight (MW 395) benzimidazole
      derivative with an EC(50) (0.16 nM) against some lab strains almost 100,000 times
      better than that of ribavirin (15 microM). Antiviral activity was confirmed for
      subgroup A and B clinical isolates of human RSV and for a bovine RSV isolate. The
      compound did not inhibit the growth of representative viruses from other
      Paramyxovirus genera, i.e. HPIV2 and Mumps Virus (genus Rubulavirus), HPIV3
      (genus Respirovirus), Measles virus (genus Morbillivirus) and hMPV. Efficacy in
      cytopathic effect inhibition assays correlated well with efficacy in virus yield
      reduction assays. A concentration of 10nM reduced RSV production 1000-fold in
      multi-cycle experiments, irrespective of the multiplicity of infection. Time of
      addition studies pointed to a dual mode of action: inhibition of virus-cell
      fusion early in the infection cycle and inhibition of cell-cell fusion at the end
      of the replication cycle. Two resistant mutants were raised and shown to have
      single point mutations in the F-gene (S398L and D486N). JNJ 2408068 was also
      shown to inhibit the release of proinflammatory cytokines IL-6, IL-8 and Rantes
      from RSV-infected A549 cells.

PMID- 14638398
TI  - Short duration aerosols of JNJ 2408068 (R170591) administered prophylactically or
      therapeutically protect cotton rats from experimental respiratory syncytial virus
      infection.
AB  - Cotton rats exposed to continuous small droplet aerosols of 2[[2-[[1-(2
      aminoethyl)-4-piperidinyl]amino]-4-methyl-1H-benzimidazol-1-yl]methyl]-6-methyl-3
      pyridinol (JNJ 2408068) or its hydrochloric salt for only 15 min, one day prior
      to virus inoculation or one day after, were significantly protected from
      pulmonary respiratory syncytial virus (RSV) infection compared to control animals
      similarly infected but exposed to aerosols of placebo at these times. No evidence
      of toxicity was seen in any of these animals or in cotton rats administered 10
      times the minimum cotton rat efficacious dose (i.e. 10x0.39 mg of active compound
      per kilogram of body weight) for four continuous days. The marked selective
      antiviral activity observed in the cotton rats mirrored that seen for these
      compounds in cytotoxicity and antiviral assays performed against RSV in vitro.
      Plasma kinetics and tissue distribution of JNJ 2408068 in cotton rats following
      inhalation were determined in separate experiments performed using conditions
      similar to those utilized in the in vivo efficacy studies. The data from these
      experiments indicated that significant levels of the test compound were delivered
      to the lungs of exposed animals, but that extrapulmonary distribution was
      limited.

PMID- 14638399
TI  - Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral
      control.
AB  - To understand the role of cytotoxic T cells in liver damage and viral control, we
      used human histocompatibility leukocyte antigen (HLA)-peptide tetramers that
      allow direct ex vivo quantification of circulating and liver-infiltrating HBV
      specific CD8 cells. Studies were carried out in two groups of patients, one
      without liver inflammation and minimal HBV replication and the other with liver
      damage and inflammation along with a high level of viral replication. Contrary to
      expectation, a high frequency of intrahepatic HBV-specific CD8 cells was found in
      the former group, i.e., the absence of hepatic immunopathology. In the
      replicating viraemic group, the virus specific T cells were diluted among the
      liver infiltrates; although with the massive cellular infiltration that was
      present, the absolute number was similar. It was also shown that in the low
      viraemia group the reservoir of CD8+ cells present in the circulation was able to
      expand after specific virus recognition and that this was not detectable in
      highly viraemic patients with liver inflammation. These results show that
      inhibition of virus replication can be independent of liver damage and when the
      HBV-specific CD8 response is unable to control virus replication it may
      contribute to liver pathology not only directly but by causing recruitment of non
      virus specific T cells.

PMID- 14638400
TI  - The nucleocapsid of the hepatitis B virus: a remarkable immunogenic structure.
AB  - The hepatitis B virus nucleocapsid or core antigen is extremely immunogenic
      during infection and after immunization. This review summarizes several features
      of the nucleocapsid which explain this exceptionally high immunogenicity: a
      unique three-dimensional folding, the presence of a region that interacts with
      immunoglobulins outside the classical antibody-binding site, the presence of many
      CD4+ T cell epitopes, and the presence of encapsidated nucleic acids. Because of
      these features, nucleocapsids efficiently interact and activate antigen
      presenting cells, especially nai;ve B cells. This leads to the generation of a
      dominant Th1 immunity phenotype and the secretion of high levels of IgM and IgG
      anti-nucleocapsid antibodies.

PMID- 14638401
TI  - Mutations of the surface protein of hepatitis B virus.
AB  - Neutralizing antibodies induced by immunization against hepatitis B infection are
      targeted to the conformational epitopes of the common a determinant of the
      surface antigen. However, amino acid substitutions within this region of the
      surface protein of the virus, particularly in the region of amino acid 137-147
      allow replication of hepatitis B virus in vaccinated subjects, since antibodies
      induced by current vaccines do not recognize crucial changes in the surface
      antigen domain. The G145R mutant is replication competent and is stable, and it
      appears to be the most common variant. There is evidence that these mutants may
      not be detected by current screening tests and diagnostic reagents.
      Epidemiological monitoring of hepatitis B virus surface mutants is essential.

PMID- 14638402
TI  - Doctor to patient transmission of hepatitis B virus: implications of HBV DNA
      levels and potential new solutions.
AB  - Hepatitis B virus (HBV)-infected health care workers (HCWs) can infect patients
      undergoing exposure prone procedures. Until now reviews have focused on the
      problem of the HBeAg-positive HCWs. After transmission of HBV by HBeAg-negative
      surgeons, the focus of Public Health Policy in the UK and the Netherlands has
      changed from HBeAg status to serum HBV DNA level. Viral load and the volume of
      blood transmitted determine the transmission risk of HBV. We have estimated the
      number of infectious particles transmitted by needlesticks, in comparison with
      those attributed in maternal-fetal transfusion. The blood volume transmitted by
      needlestick is roughly 1-30% of that of delivery. As vertical transmission with
      maternal HBV DNA levels below 10(7) g Eq./ml is rarely documented, HBV
      transmission by needlesticks is, according to our assumptions, unlikely to occur
      with HBV DNA levels below 10(7) g Eq./ml. Sera of transmitting HCWs contained HBV
      DNA levels between 5.0 x 10(9) and 6.35 x 10(4) g Eq./ml. Interpretation of these
      levels is hampered as the sera were taken at least 3 months after transmission.
      To prevent both loss of expertise and nosocomial infection, highly viremic HCWs
      can be offered antiviral therapy. Lamivudine and alpha-interferon can now be
      complemented with adefovir, tenofovir and entecavir to provide effective new
      therapies for chronic HBV-infected HCWs.

PMID- 14638403
TI  - Pegylated interferons for chronic hepatitis B.
AB  - Conventional interferon therapy has been used for the treatment of chronic
      hepatitis B (CHB) for many decades. However, the use of interferon has been
      limited by its short half-life and high incidence of dose-related side effects. A
      meta-analysis investigating the short- and long-term consequences of interferon
      therapy showed that, whilst interferon therapy was beneficial in the short term,
      resulting in normalization of alanine aminotransferase (ALT) levels, loss of
      HBeAg, 'e' seroconversion and suppression of hepatitis B virus (HBV) DNA, the
      long-term benefits were less substantial. Pegylation of interferon (peginterferon
      alpha-2a [40 kDa]) led to improved pharmacokinetic and pharmacodynamic profiles,
      which translated to superior efficacy compared with conventional, nonpegylated
      interferon, in the treatment of chronic hepatitis C. A phase II study
      investigated the safety and efficacy of peginterferon alpha-2a (40 kDa) in the
      treatment of chronic hepatitis B. The results demonstrated a rapid and dramatic
      reduction in HBV DNA levels, HBeAg clearance and normalization of ALT with
      peginterferon alpha-2a (40 kDa) compared with conventional interferon.
      Furthermore, peginterferon alpha-2a (40 kDa) conferred a notably improved
      treatment response in patients with 'difficult-to-treat' hepatitis B infection.
      In conclusion, peginterferon alpha-2a (40 kDa) is a promising emerging therapy
      for CHB.

PMID- 14638404
TI  - Replication of the hepatitis C virus in cell culture.
AB  - Studies of hepatitis C virus (HCV) replication in cell culture have been greatly
      facilitated by the development of genetically engineered viral genomes that are
      capable of self-amplifying to high levels in a human hepatoma cell line. Since
      the original description of this 'replicon' model in 1999, important improvements
      have been made. Most notably, cell culture adaptive mutations were identified in
      various non-structural proteins that enhance RNA replication by several orders of
      magnitude. More recently, the permissiveness of the host cell was determined as
      an additional important factor contributing to efficient RNA replication. These
      discoveries allowed the development of transient replication assays, selectable
      full length genomes and a variety of novel replicons that will be useful for
      basic studies and facilitate the development of antiviral drugs. Ultimately, the
      replicon system may help to decipher the molecular basis of interferon-alpha (IFN
      alpha) resistance.

PMID- 14638405
TI  - Membrane association of hepatitis C virus nonstructural proteins and
      identification of the membrane alteration that harbors the viral replication
      complex.
AB  - Hepatitis C virus (HCV) replicates its genome in a membrane-associated complex
      composed of viral proteins, replicating RNA, and altered cellular membranes.
      Determinants for membrane association of the HCV nonstructural proteins involved
      in genome replication have been defined. In addition, a specific membrane
      alteration, designated membranous web, was recently identified as the site of
      viral RNA synthesis and, therefore, represents the HCV replication complex. These
      findings add to our current understanding of the HCV life cycle and may
      ultimately allow to design novel antiviral strategies against hepatitis C.

PMID- 14638406
TI  - Multifaceted functions of B cells in chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) elicits T- and B-cell responses which are believed to
      play an important role in infection control. B cells have generally been
      neglected because they do not seem to significantly influence the course of HCV
      infection. In this review, B lymphocytes are viewed both as classical antibody
      producing cells, with the hypervariable region 1 being a biologically relevant
      target protein and as a model of virus-host interaction in lymphoproliferative
      disorders characteristic of persistent microbial infections.

PMID- 14638407
TI  - Hepatitis C virus core protein transactivates the inducible nitric oxide synthase
      promoter via NF-kappaB activation.
AB  - Intrahepatic levels of the inducible nitric oxide synthase (iNOS) are increased
      in chronic hepatitis C patients. As iNOS gene promoter contains Nuclear Factor
      (NF)-kappaB binding sites and hepatitis C virus (HCV) core protein activates NF
      kappaB, the aim of this work was to study if HCV core protein transactivates iNOS
      promoter through NF-kappaB activation. iNOS mRNA and protein were determined by
      RT-PCR and western blot in HepG2 cells. The effect of HCV core protein on iNOS
      promoter was assayed by cotransfecting HepG2 cells with the core protein
      expression plasmid pHCV-Co and p1iNOS-CAT or p2iNOS-CAT plasmids. Formation of NF
      kappaB-DNA complexes was determined by electrophoretic mobility shift assay.
      Transfection of HepG2 cells with pHCV-Co plasmid results in an increase in iNOS
      mRNA and protein levels. Cotransfection with pHCV-Co and p1iNOS-CAT or p2iNOS-CAT
      plasmids results in a transactivation of iNOS promoter, the presence of the
      proximal NF-kappaB binding site in the promoter being sufficient for the
      transactivation. Furthermore, the HCV core protein increases the formation of
      complexes between NF-kappaB and its binding sequence in the iNOS promoter. The
      expression of the NF-kappaB inhibitor IKB reverts the effect of the HCV core
      protein on the iNOS promoter. In conclusion, HCV core protein transactivates iNOS
      gene promoter through NF-kappaB activation.

PMID- 14638409
TI  - Decrease in the hepatitis C virus (HCV) prevalence in hemodialysis patients in
      Spain: effect of time, initiating HCV prevalence studies and adoption of
      isolation measures.
AB  - The effectiveness of isolation measures to prevent hepatitis C virus (HCV)
      infection in hemodialysis units is a controversial issue. Strict adherence to the
      universal infection control precautions has been deemed adequate to prevent
      nosocomial transmission of HCV. Subsequently, however, select isolation measures,
      such as the clustering of HCV positive patients in a defined sector of the unit,
      have been adopted, specially for those units with a high HCV prevalence and when
      the personnel-patient ratio was such that it could involuntary favor the break of
      the universal precautions. In this Multicenter Spanish Study on HCV in Dialysis,
      the importance of both time and isolation measures led to a decrease of HCV
      prevalence. Time was the most important factor (although interacting with the
      isolation measures) and was independent of the initial HCV prevalence.

PMID- 14638408
TI  - Hepatitis C virus infection and liver steatosis.
AB  - The mechanism by which the hepatitis C virus (HCV) causes chronic, progressive
      liver damage is unknown. Factors other than the virus itself have been
      implicated. The role of liver steatosis has been recently studied. Hepatic
      steatosis is a common histological finding occurring in more 50% of patients with
      chronic hepatitis C. Both host and viral factors have been demonstrated to play
      an important role in its development. In those patients infected with genotype 1,
      steatosis appears to be due to the co-existence of Non-Alchoholic SteatoHepatitis
      (NASH) with HCV and associated with an increased body mass index (BMI). Some
      recent observations suggest that steatosis may be of viral origin and related to
      genotype 3. This fact raises the possibility of a direct effect of specific viral
      sequences on the pathogenesis of lipid accumulation. Furthermore, hepatic
      steatosis attributed to genotype 3 correlates directly with serum and
      intrahepatic titters of HCV RNA. The resolution of steatosis after successful
      antiviral therapy as well as steatosis being a sign of recurrent HCV infection in
      patients with genotype 3 add convincing evidence that steatosis is viral related.
      The pathogenic mechanism induced by genotype 3 is speculative. A correlation
      between steatosis, intrahepatic HCV RNA and core protein expression suggest a
      direct effect. Further support is provided by the finding that HCV core protein
      induces steatosis in transgenic mice. Another possibility relates to interaction
      with hepatic triglyceride turnover. In conclusion, for patients infected with
      genotype 1, BMI has a role in the pathogenesis of steatosis while in those
      infected with genotype 3, steatosis may be due to a virus-specific cytopathic
      effect. Regardless of etiology, the contribution of both to liver fibrosis
      progression seems accepted.

PMID- 14638410
TI  - Combined antiviral options for the treatment of chronic hepatitis C.
AB  - In the absence of antiviral treatment, chronic hepatitis C virus (HCV) infection
      is a liver disease characterized by the development of necroinflammatory changes
      and progressive liver fibrosis, leading to cirrhosis, end-stage liver disease and
      hepatocellular carcinoma (HCC). The approval of ribavirin in combination therapy
      regimens with interferon (IFN) dramatically improved therapy. Another advance was
      the introduction of pegylated IFNs, which allow a once-weekly subcutaneous
      administration and show more favorable pharmacokinetics and greater efficacy. Two
      forms are available: pegylated IFN alpha-2b (12 kDa) (1.5 microg/kg) and
      pegylated IFN alpha-2a (40 kDa) (fixed dosage of 180 microg). Ribavirin is
      administered orally, at doses > or =10.6 mg/kg, resulting in higher sustained
      virological responses (SVR) than IFN monotherapy. The highest SVR rates are
      attained with pegylated IFNs in combination with ribavirin. Factors associated
      with treatment outcome include HCV genotype, viral load, body weight, age,
      cirrhosis or bridging fibrosis, coinfection with HIV or hepatitis B virus, and
      treatment adherence and tolerance. Currently, the main therapeutic challenges
      ahead are: (a) the dosage optimization of pegylated IFNs and ribavirin according
      to the patients' characteristics; and (b) to evaluate the efficacy and safety of
      this combination therapy for difficult-to-treat patients, such as nonresponders,
      cirrhotics, transplant recipients, renal disease patients or those coinfected
      with HIV.

PMID- 14638411
TI  - Etiology, natural history and treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is linked to environmental, dietary and lifestyle
      factors. Patients with cirrhosis and chronic carriage of hepatitis B virus (HBV)
      are at risk for HCC at annual rates of 3%. HCC risk is particularly high in
      patients with evidence of cirrhosis and histological markers of increased liver
      cell proliferation. In addition, thrombocytopenia, prolonged prothrombin time and
      over 55 years of age also predict the development of HCC. Treatment options are
      defined according to the presence or absence of cirrhosis, number and size of
      tumors, and degree of hepatic decompensation. Hepatic resection is the primary
      intervention for these few patients with tumor but surrounding normal liver
      tissue and well preserved hepatic function. Under such circumstances, the
      cumulative 5-year survival is approximately 45%. Liver transplantation (OLT)
      provides long term survivals (90% at 5 years) in patients with a HCC discovered
      by chance as a minute nodule and of 75% in patients with viral cirrhosis and a
      single <5 cm tumor or fewer than three <3 cm nodes. Since liver transplantation
      cannot be offered to most patients with HCC, hepatic resection remains the
      primary therapeutic option; 5-year survival of 50% is anticipated in patients
      with compensated cirrhosis and <5 cm of tumor and 75% for those with moderate
      portal hypertension and normal serum bilirubin values. Ultrasound-guided tumor
      injection with absolute ethanol or tumor thermoablation with radiofrequency
      provide similar survival rates but with fewer complications. Whether arterial
      chemoembolization benefits patients with HCC remains controversial.

PMID- 14638412
TI  - Proceedings of the X International Symposium on Viral Hepatitis. Madrid, Spain,
      23-24 January 2003.

PMID- 14638413
TI  - Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators:
      exploiting the metabolic spectrum by controlling alternative gene programs.
AB  - The Crp-Fnr regulators, named after the first two identified members, are DNA
      binding proteins which predominantly function as positive transcription factors,
      though roles of repressors are also important. Among over 1200 proteins with an N
      terminally located nucleotide-binding domain similar to the cyclic adenosine
      monophosphate (cAMP) receptor protein, the distinctive additional trait of the
      Crp-Fnr superfamily is a C-terminally located helix-turn-helix motif for DNA
      binding. From a curated database of 369 family members exhibiting both features,
      we provide a protein tree of Crp-Fnr proteins according to their phylogenetic
      relationships. This results in the assembly of the regulators ArcR, CooA, CprK,
      Crp, Dnr, FixK, Flp, Fnr, FnrN, MalR, NnrR, NtcA, PrfA, and YeiL and their
      homologs in distinct clusters. Lead members and representatives of these groups
      are described, placing emphasis on the less well-known regulators and target
      processes. Several more groups consist of sequence-derived proteins of unknown
      physiological roles; some of them are tight clusters of highly similar members.
      The Crp-Fnr regulators stand out in responding to a broad spectrum of
      intracellular and exogenous signals such as cAMP, anoxia, the redox state,
      oxidative and nitrosative stress, nitric oxide, carbon monoxide, 2-oxoglutarate,
      or temperature. To accomplish their roles, Crp-Fnr members have intrinsic sensory
      modules allowing the binding of allosteric effector molecules, or have prosthetic
      groups for the interaction with the signal. The regulatory adaptability and
      structural flexibility represented in the Crp-Fnr scaffold has led to the
      evolution of an important group of physiologically versatile transcription
      factors.

PMID- 14638414
TI  - Alcohol dehydrogenases from thermophilic and hyperthermophilic archaea and
      bacteria.
AB  - Many studies have been undertaken to characterise alcohol dehydrogenases (ADHs)
      from thermophiles and hyperthermophiles, mainly to better understand their
      activities and thermostability. To date, there are 20 thermophilic archaeal and
      17 thermophilic bacterial strains known to have ADHs or similar enzymes,
      including the hypothetical proteins. Some of these thermophiles are found to have
      multiple ADHs, sometimes of different types. A rigid delineation of amino acid
      sequences amongst currently elucidated thermophilic ADHs and similar proteins is
      phylogenetically apparent. All are NAD(P)-dependent, with one exception that
      utilises the cofactor F(420) instead. Within the NAD(P)-dependent group, the
      thermophilic ADHs are orderly clustered as zinc-dependent ADHs, short-chain ADHs,
      and iron-containing/activated ADHs. Distance matrix calculations reveal that
      thermophilic ADHs within one type are homologous, with those derived from a
      single genus often showing high similarities. Elucidation of the enzyme activity
      and stability, coupled with structure analysis, provides excellent information to
      explain the relationship between them, and thermophilic ADHs diversity.

PMID- 14638415
TI  - Ammonium assimilation and nitrogen control in Corynebacterium glutamicum and its
      relatives: an example for new regulatory mechanisms in actinomycetes.
AB  - Nitrogen is an essential component of nearly all complex macromolecules in a
      bacterial cell, such as proteins, nucleic acids and cell wall components.
      Accordingly, most prokaryotes have developed elaborate control mechanisms to
      provide an optimal supply of nitrogen for cellular metabolism and to cope with
      situations of nitrogen limitation. In this review, recent advances in our
      knowledge of ammonium uptake, its assimilation, and related regulatory systems in
      Corynebacterium glutamicum, a Gram-positive soil bacterium used for the
      industrial production of amino acids, are summarized and discussed with respect
      to the situation in the bacterial model organisms, Escherichia coli and Bacillus
      subtilis, and in comparison to the situation in other actinomycetes, namely in
      mycobacteria and streptomycetes. The regulatory network of nitrogen control in C.
      glutamicum seems to be a patchwork of different elements. It includes proteins
      similar to the UTase/GlnK pathway of E. coli and expression regulation by a
      repressor protein as in B. subtilis, but it lacks an NtrB/NtrC two-component
      signal transduction system. Furthermore, the C. glutamicum regulation network has
      unique features, such as a new sensing mechanism. Based on its extremely well
      investigated central metabolism, well-established molecular biology tools, a
      public genome sequence and a newly-established proteome project, C. glutamicum
      seems to be a suitable model organism for other corynebacteria, such as
      Corynebacterium diphtheriae and Corynebacterium efficiens.

PMID- 14638416
TI  - Exploiting the yeast Saccharomyces cerevisiae for the study of the organization
      and evolution of complex genomes.
AB  - Yeast artificial chromosome (YAC) cloning systems have advanced the analysis of
      complex genomes considerably. They permit the cloning of larger fragments than do
      bacterial artificial chromosome systems, and the cloned material is more easily
      modified. We recently developed a novel YAC cloning system called transformation
      associated recombination (TAR) cloning. Using in vivo recombination in yeast, TAR
      cloning selectively isolates, as circular YACs, desired chromosome segments or
      entire genes from complex genomes. The ability to do that without constructing a
      representative genomic library of random clones greatly facilitates analysis of
      gene function and its role in disease. In this review, we summarize how
      recombinational cloning techniques have advanced the study of complex genome
      organization, gene expression, and comparative genomics.

PMID- 14638417
TI  - How to detect Toxoplasma gondii oocysts in environmental samples?
AB  - Detection of Toxoplasma gondii oocysts in environmental samples is a great
      challenge for researchers as this coccidian parasite can be responsible for
      severe infections in humans and in animals via ingestion of a single oocyst from
      contaminated water, soil, fruits or vegetables. Despite field investigations,
      oocysts have been rarely recovered from the environment due to the lack of
      sensitive methods. Immunomagnetic separation, fluorescence-activated cell
      sorting, and polymerase chain reaction have recently shown promising use in
      detection of protozoa from complex matrices. Such procedures could be applied to
      T. gondii detection, if studies on the antigenic and biochemical composition of
      the oocyst wall are completed. Using such methods, it will be possible to assess
      the occurrence, prevalence, viability and virulence of T. gondii oocysts in
      environmental matrices and specify sources of human and animal contamination.

PMID- 14638418
TI  - Opportunities to improve fiber degradation in the rumen: microbiology, ecology,
      and genomics.
AB  - The degradation of plant cell walls by ruminants is of major economic importance
      in the developed as well as developing world. Rumen fermentation is unique in
      that efficient plant cell wall degradation relies on the cooperation between
      microorganisms that produce fibrolytic enzymes and the host animal that provides
      an anaerobic fermentation chamber. Increasing the efficiency with which the rumen
      microbiota degrades fiber has been the subject of extensive research for at least
      the last 100 years. Fiber digestion in the rumen is not optimal, as is supported
      by the fact that fiber recovered from feces is fermentable. This view is
      confirmed by the knowledge that mechanical and chemical pretreatments improve
      fiber degradation, as well as more recent research, which has demonstrated
      increased fiber digestion by rumen microorganisms when plant lignin composition
      is modified by genetic manipulation. Rumen microbiologists have sought to improve
      fiber digestion by genetic and ecological manipulation of rumen fermentation.
      This has been difficult and a number of constraints have limited progress,
      including: (a) a lack of reliable transformation systems for major fibrolytic
      rumen bacteria, (b) a poor understanding of ecological factors that govern
      persistence of fibrolytic bacteria and fungi in the rumen, (c) a poor
      understanding of which glycolyl hydrolases need to be manipulated, and (d) a lack
      of knowledge of the functional genomic framework within which fiber degradation
      operates. In this review the major fibrolytic organisms are briefly discussed. A
      more extensive discussion of the enzymes involved in fiber degradation is
      included. We also discuss the use of plant genetic manipulation, application of
      free-living lignolytic fungi and the use of exogenous enzymes. Lastly, we will
      discuss how newer technologies such as genomic and metagenomic approaches can be
      used to improve our knowledge of the functional genomic framework of plant cell
      wall degradation in the rumen.

PMID- 14638419
TI  - Shiga toxins and apoptosis.
AB  - The enteric pathogens Shigella dysenteriae serotype 1 and Shiga toxin-producing
      Escherichia coli (STEC) cause bloody diarrheal diseases that may progress to life
      threatening extraintestinal complications. Although the S. dysenteriae and STEC
      differ in the expression of a number of virulence determinants, they share the
      capacity to produce one or more potent cytotoxins, called Shiga toxins (Stxs).
      Following the ingestion of the organisms, the expression of Stxs is critical for
      the development of vascular lesions in the colon, kidneys and central nervous
      system. It has been known for some time that following the intracellular routing
      of Stxs to the endoplasmic reticulum and nuclear membrane, the toxins translocate
      into the cytoplasm and target ribosomes for damage. However, numerous recent
      studies have shown that Stxs trigger programmed cell death signaling cascades in
      intoxicated cells. The mechanisms of apoptosis induction by these toxins are
      newly emerging, and the data published to date suggest that the toxins may signal
      apoptosis in different cells types via different mechanisms. Here we review the
      Stxs and the known mechanistic aspects of Stx-induced apoptosis, and present a
      model of apoptosis induction.

PMID- 14638420
TI  - Indole-3-butyric acid (IBA) production in culture medium by wild strain
      Azospirillum brasilense.
AB  - Some microorganisms found in the soil are able to produce substances which
      regulate plant growth. In this study, we show the presence of a substance
      associated with auxin activity, identified as indole-3-butyric acid (IBA), in
      Azospirillum brasilense UAP 154 growth medium. A. brasilense was grown and
      indolic compounds were extracted from the supernatant. These were then analyzed
      by high performance liquid chromatography (HPLC), gas chromatography and gas
      chromatography mass spectrometry. The retention time was similar to those of the
      authentic IBA standard. The compound obtained from HPLC was collected and applied
      to maize seedlings (Zea mays), inducing biological activity along the roots,
      similar to that induced by an authentic IBA standard.

PMID- 14638421
TI  - Antimicrobial resistance in Gram-negative bacilli isolated from infant formulas.
AB  - A total of 90 samples of infant formula (IF) were collected from the lactary of a
      teaching hospital, during a 4-month period from July to August 1999. The sanitary
      conditions of the formulas were analyzed, and a physiological characterization of
      Gram-negative bacillus isolates and antimicrobial susceptibility testing were
      performed. Colony counts were considered to be unacceptable for the majority of
      the IF samples and the contamination rates were related to inadequate handling.
      Coliforms (35 degrees C and 45 degrees C growth) were detected in most of the IF
      tested. Klebsiella pneumoniae, Citrobacter freundii, Cedacea davisae, Klebsiella
      planticola and Enterobacter cloacae were the isolates most commonly identified.
      Antimicrobial susceptibility testing showed significant resistance rates,
      particularly to amoxicillin/clavulanic acid, cefoxitin, cephalotin or ampicillin.
      One extended-spectrum beta-lactamase-producing K. pneumoniae strain was also
      recovered.

PMID- 14638422
TI  - Multidrug-resistant Pseudomonas aeruginosa strains harbouring R-plasmids and AmpC
      beta-lactamases isolated from hospitalised burn patients in a tertiary care
      hospital of North India.
AB  - The present study was designed to determine resistance rates and patterns in
      Pseudomonas aeruginosa isolates obtained from hospitalised burn patients in an
      Indian tertiary care hospital. To that end, we isolated plasmid(s) from the
      multidrug-resistant isolates, demonstrated the plasmid-mediated resistance by
      curing and transformation experiments, and screened all the isolates for the
      occurrence of AmpC beta-lactamases. Thirty isolates of P. aeruginosa were
      analysed for the presence of antibiotic resistance. Plasmid-curing experiments
      and AmpC beta-lactamase detection were performed on all the isolates and seven
      isolates showing the most common antibiotic resistance pattern were selected for
      plasmid isolation and transformation experiments. All 30 isolates were multidrug
      resistant and the majority (83.3%) of isolates were resistant to seven or more
      antibiotics, out of 11 antibiotics tested including anti-pseudomonal and non-anti
      pseudomonal antimicrobial drugs. The most striking feature was the presence of
      resistance to amikacin. A 48.5-kb plasmid was isolated from the isolates. Curing
      and transformation experiments showed that resistance to amikacin was plasmid
      mediated. Phenotypic screening for the occurrence of AmpC beta-lactamases showed
      that 20% of isolates were AmpC producers whereas 10% of isolates were
      characterised as 'indeterminate' for AmpC enzyme. In conclusion, a markedly high
      (56.7%) resistance to amikacin was noted in the present study. Amikacin
      resistance was determined to be plasmid-encoded and the presence of an AmpC beta
      lactamase was inferred in 20% of isolates. This is among the first reports
      regarding the emergence of plasmid-mediated resistance to amikacin and the
      occurrence of AmpC beta-lactamases in P. aeruginosa strains from India.

PMID- 14638423
TI  - Comparison of two RT-PCR methods for quantifying ampC specific transcripts in
      Escherichia coli strains.
AB  - In Escherichia coli, beta-lactam resistance usually depends on beta-lactamase
      production. AmpC chromosomal cephalosporinase hyperproduction is generally due to
      mutations in the ampC gene promoter. In order to study ampC expression in E. coli
      clinical strains, we have compared two methods: conventional and real-time
      reverse transcription-polymerase chain reaction (RT-PCR). With both methods, ampC
      mRNA was found to be greatly increased in strains presenting -42 or -32 mutations
      in the ampC promoter, and moderately increased when a -11 mutation was present in
      the Pribnow box. Real-time RT-PCR represents a powerful tool combining
      amplification, fluorescent detection and analysis.

PMID- 14638424
TI  - Involvement of region 4 of the sigma70 subunit of RNA polymerase in
      transcriptional activation of the lux operon during quorum sensing.
AB  - Quorum sensing-dependent activation of the luminescence (lux) genes of Vibrio
      fischeri relies on the formation of a complex between the autoinducer molecule, N
      (3-oxohexanoyl)-L-homoserine lactone, and the autoinducer-dependent
      transcriptional activator LuxR. In its active conformation, LuxR binds to a site
      known as the lux box centered at position -42.5 relative to the luxI
      transcriptional start site and is thought to function as an ambidextrous
      activator capable of making multiple contacts with RNA polymerase (RNAP). The
      specific role of region 4 of the Escherichia coli sigma70 subunit of RNAP in LuxR
      dependent activation of the luxI promoter has been investigated. Single-round
      transcription assays were performed in the presence of purified LuxRDeltaN, the
      autoinducer-independent C-terminal domain of LuxR, and a variant RNAP which
      contained a C-terminally truncated sigma70 subunit devoid of region 4. Results
      indicated that region 4 is essential for LuxRDeltaN-dependent luxI transcription,
      therefore 16 single and two triple alanine substitutions in region 4.2 of sigma70
      between amino acid residues 590 and 613 were examined for their effects on LuxR-
      and LuxRDeltaN-dependent transcription at the luxI promoter. Taken together, the
      analyses performed on these variants of RpoD suggest that some individual
      residues in region 4.2 are important to the mechanism of activator-dependent
      transcription initiation under investigation.

PMID- 14638425
TI  - A three-tiered approach to differentiate Listeria monocytogenes biofilm-forming
      abilities.
AB  - The purpose of this research was to develop a system for cultivating and
      evaluating Listeria monocytogenes biofilms that produces consistent and reliable
      results. A three-tiered approach was used to evaluate biofilm-forming abilities
      of three L. monocytogenes strains that were originally associated with
      listeriosis outbreaks. A L. monocytogenes 'honeycomb' biofilm structure was
      described. L. monocytogenes strains Scott A and V7 were comparable in developing
      biofilm network structures and F2365 was less effective in forming biofilm. This
      three-tiered method can be very useful for further biofilm studies.

PMID- 14638426
TI  - The csbX gene of Azotobacter vinelandii encodes an MFS efflux pump required for
      catecholate siderophore export.
AB  - The csbX gene of Azotobacter vinelandii was regulated in an iron-repressible
      manner from a divergent promoter upstream of the catecholate siderophore
      biosynthesis (csb) operon and was predicted to encode an efflux pump of the major
      facilitator superfamily. Other proteins that were most similar to CsbX were
      encoded by genes found in the catecholate siderophore biosynthesis operons of
      Aeromonas hydrophila and Stigmatella aurantiaca. Inactivation of csbX resulted in
      57-100% decrease in the amount of catecholates released when compared to the wild
      type in iron-limited medium. CsbX was most important for the export of the high
      affinity chelator protochelin with the majority of the catecholates released by
      csbX mutants being the protochelin intermediates azotochelin and aminochelin.

PMID- 14638427
TI  - The development of phenanthrene catabolism in soil amended with transformer oil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants
      frequently associated with light non-aqueous-phase liquids (LNAPLs) in soil.
      Microbial degradation comprises a major loss process for PAHs in the environment.
      Various laboratory studies, using known degraders, have shown reduced or enhanced
      mineralisation of PAHs when dissolved in different LNAPLs. Effects due to the
      presence of LNAPLs on indigenous micro-organisms, however, are not fully
      understood. A pristine pasture soil was spiked with [14C]phenanthrene and
      transformer oil to 0, 0.01 and 0.1%, and incubated for 180 days. The catabolic
      potential of the soil towards phenanthrene was assessed periodically during
      ageing. The extent of the lag phase (prior to >5% mineralisation), maximum rates
      and overall extents of mineralisation observed during the course of a 14-day
      bioassay appeared to be dependent upon phenanthrene concentration, the presence
      of transformer oil, and soil-contaminant contact time. Putatively, transformer
      oil enhanced acclimation and facilitated the development of measurable catabolic
      activity towards phenanthrene in a previously uncontaminated pasture soil. Exact
      mechanisms for the observed enhancement, longer-term fate/degradation of the oil
      and residual phenanthrene, and effects of the presence of the oil on the
      indigenous microbes over extended time frames warrant further investigation.

PMID- 14638428
TI  - Reduced amounts of LPS affect both stress tolerance and virulence of Salmonella
      enterica serovar Dublin.
AB  - Signature-tagged mutagenesis (STM) is a widely used technique for identification
      of virulence genes in bacterial pathogens. While this approach often generates a
      large number of mutants with a potential reduction in virulence a major task is
      subsequently to determine the mechanism by which the mutations influence
      virulence. Presently, we have characterised a Salmonella enterica serovar Dublin
      STM mutant that, in addition to having reduced virulence, was also impaired when
      growing under various stress conditions. The mutation mapped to the manC (rfbM)
      gene of the O-antigen gene cluster involved in O-antigen synthesis. The O-antigen
      is a component of the lipopolysaccharide (LPS) forming a unique constituent of
      the outer membrane of Gram-negative bacteria. While mutations in the O-antigen
      genes usually eliminate the entire O-antigen side chain we found that the
      transposon mutant produced intact O-antigen, however, the mutation reduced the
      amount of LPS.

PMID- 14638429
TI  - Characterization of plasma membrane respiratory chain and ATPase in the
      actinomycete Nonomuraea sp. ATCC 39727.
AB  - We have characterized the respiratory system of the aerobic actinomycete
      Nonomuraea sp. ATCC 39727. The plasma membrane of the microorganism is shown to
      contain a protonmotive respiratory chain and H+-ATPase. The respiratory chain is
      made up of a rotenone-sensitive NADH-quinone oxidoreductase, a four subunits aa3
      type cytochrome c oxidase and a bc1 complex. The H+-ATPase is characterized as an
      F0F1-type on the basis of its sensitivity to specific inhibitors; the enzyme is
      also inhibited by mM concentrations of Ca2+. The activity of the respiratory
      chain increases during the exponential growth phase, but is depressed in the
      stationary phase. The H+-ATPase activity reaches, as the respiratory chain, a
      maximal activity at the end of the exponential growth phase and then remains
      constant in the stationary phase.

PMID- 14638430
TI  - Quantification of disease progression of several microbial pathogens on
      Arabidopsis thaliana using real-time fluorescence PCR.
AB  - An accurate monitoring of disease progression is important to evaluate disease
      susceptibility phenotypes. Over the years, Arabidopsis thaliana has become the
      model species to serve as a host in plant-pathogen interactions. Despite the
      efforts to study genetic mechanisms of host defense, little efforts are made for
      a thorough pathogen assessment, often still depending on symptomology. This
      manuscript describes the use of real-time polymerase chain reaction (PCR) to
      assess pathogen growth in the host Arabidopsis for a number of frequently studied
      pathogens. A wide range of correlations between pathogen biomass and fluorescence
      is demonstrated, demonstrating the theoretical sensitivity of the technique. It
      is also demonstrated that host DNA does not interfere with the quantification of
      pathogen DNA over a wide range. Finally, quantification of pathogen biomass in
      different plant genotypes with a varying degree of resistance shows the
      capability of this technique to be used for assessment of pathogen development in
      disease progression.

PMID- 14638431
TI  - Comparative analysis of Borrelia isolates from southeastern USA based on randomly
      amplified polymorphic DNA fingerprint and 16S ribosomal gene sequence analyses.
AB  - Fifty-three southern USA Borrelia isolates were characterized using randomly
      amplified polymorphic DNA fingerprinting analysis (RAPD). Twenty-nine types were
      recognized among 37 B. andersonii strains, seven types among eight B. bissettii
      strains, and seven types among seven B. burgdorferi sensu stricto strains. Strain
      TXW-1 formed a separate RAPD type. Nearly complete sequences of the rrs genes
      from 17 representative southern Borrelia were determined. The similarity values
      were found to be 96-100% within the B. burgdorferi sensu lato (s.l.) complex, 94
      99% among the relapsing fever borreliae, and 93-99% between the two complexes.
      Phylogenetic analysis indicated that all the Borrelia strains we analyzed could
      be divided into two parts: the B. burgdorferi s.l. complex and the relapsing
      fever borreliae complex. TXW-1 segregated with the North American relapsing fever
      borreliae and formed a separate subbranch.

PMID- 14638432
TI  - A plasmid encoding a combination of mosquito-larvicidal genes from Bacillus
      thuringiensis subsp. israelensis and Bacillus sphaericus confers toxicity against
      a broad range of mosquito larvae when expressed in Gram-negative bacteria.
AB  - A recombinant plasmid harboring cry4A, cry4B and cry11A from Bacillus
      thuringiensis subsp. israelensis and binary toxin genes from Bacillus sphaericus
      has been constructed. The three cry genes were placed under the control of the
      cry4B promoter whereas the binary toxin gene was controlled by its native
      promoter. The expression of toxins in Escherichia coli harboring the resulting
      plasmid, p4BDA-5142, was investigated. Cry4B expression was highest compared to
      other toxins. Although the level of toxin expression was low compared with E.
      coli expressing single toxins, the recombinant E. coli strain harboring p4BDA
      5142 exhibited broad range mosquito-larvicidal activity against all Aedes, Culex
      and Anopheles larvae. This work has shown that the development of the recombinant
      plasmid can be used to broaden the host range spectrum of the appropriate
      bacterial host for mosquito control.

PMID- 14638433
TI  - The osmotic regulator OmpR is involved in the response of Yersinia enterocolitica
      O:9 to environmental stresses and survival within macrophages.
AB  - Various environmental signals control the expression of the virulence factors in
      pathogenic Yersinia enterocolitica strains. The role of the osmotic regulator
      OmpR protein in controlling the production of Yop proteins, virulence
      determinants in Y. enterocolitica O:9 (European type) has been studied. An ompR
      deletion mutant was constructed via allelic exchange with an ompR gene of Y.
      enterocolitica mutagenized in vitro by a reverse genetic polymerase chain
      reaction (PCR)-based strategy. The ompR mutant showed a reduced ability to
      survive under conditions of various environmental stresses in vitro. In
      particular, low pH stress resulted in increased cell mortality levels. Under
      conditions of high osmolarity, the wild strain's Yop protein production was
      reduced, whereas protein levels from the mutant strain remained constant
      regardless of osmolarity variance. In J774A.1 macrophage cell culture survival of
      the ompR mutant was decidedly lower than that of the wild-type strain, suggesting
      that the OmpR protein may play a significant role in protecting cells against
      intracellular conditions associated with macrophage phagocytosis.

PMID- 14638434
TI  - Selenate reduction by Enterobacter cloacae SLD1a-1 is catalysed by a molybdenum
      dependent membrane-bound enzyme that is distinct from the membrane-bound nitrate
      reductase.
AB  - Enterobacter cloacae SLD1a-1 is capable of reducing selenium oxyanions to
      elemental selenium under both aerobic and anaerobic conditions. In this study the
      enzyme that catalyses the initial reduction of selenate (SeO4(2-)) to selenite
      (SeO3(2-)) has been localised to isolated cytoplasmic membrane fractions.
      Experiments with intact cells have shown that the putative selenate reductase can
      accept electrons more readily from membrane-impermeable methyl viologen than
      membrane-permeable benzyl viologen, suggesting that the location of the catalytic
      site is towards the periplasmic side of the cytoplasmic membrane. Enzyme activity
      was enhanced by growing cells in the presence of 1 mM sodium molybdate and
      significantly reduced in cells grown in the presence of 1 mM sodium tungstate.
      Non-denaturing polyacrylamide gel electrophoresis (PAGE) gels stained for
      selenate and nitrate reductase activity have revealed that two distinct membrane
      bound enzymes catalyse the reduction of selenate and nitrate. The role of this
      membrane-bound molybdenum-dependent reductase in relation to selenate
      detoxification and energy conservation is discussed.

PMID- 14638435
TI  - The relationship between 'wild' and 'building' isolates of the dry rot fungus
      Serpula lacrymans.
AB  - Molecular and morphological parameters of Serpula lacrymans isolates from various
      sites in the built environment in Europe and Australia were compared to similar
      parameters of 'wild' isolates from India, the Sumava Mountains (Czech Republic)
      and Mount Shasta (USA). The Indian, Czech Republic and all of the building
      isolates bar one showed identity in both molecular and morphological features.
      The Australian and the USA isolates (BF-050 and USA'94 respectively) showed
      specific morphological differences and could be separated on the basis of
      randomly amplified polymorphic deoxyribonucleic acid polymerase chain reaction
      (RAPD PCR) with the USA isolate being least closely related to the S. lacrymans
      type strain of FPRL12C. ITS sequence data revealed two base differences between
      FPRL12C and BF-050 in the 673 sequenced, nine differences between FPRL12C and
      USA'94 and 16 differences between USA'94 and the closely related organism Serpula
      himantioides. The possible evolutionary relationships between the various
      isolates are discussed along with suggestions for the origin of S. lacrymans as a
      scourge of the built environment in many temperate areas of the world.

PMID- 14638436
TI  - Adherence and autoaggregation phenotypes of a Burkholderia cenocepacia cable
      pilus mutant.
AB  - Cable pili are unique peritrichous adherence organelles expressed by certain
      strains of the opportunistic human pathogen Burkholderia cenocepacia. Cable pili
      have been proposed to facilitate binding to human epithelial cells and mucin, and
      may play a role in the ability of B. cenocepacia to colonise the respiratory
      tract of compromised hosts. In this study, a genetic approach was undertaken to
      assess the role of cable pili in mediating adherence as well as bacterial cell
      cell interactions. The cblA gene, encoding the major pilin subunit, was
      insertionally inactivated, and the resulting mutant was shown to be blocked in
      CblA expression and in cable pilus morphogenesis. Although non-piliated, the cblA
      mutant was not defective in adherence to either porcine mucin or to cultured A549
      human respiratory epithelial cells. Microscopic and flow cytometric analyses of
      B. cenocepacia cultures revealed that cable pilus expression facilitated the
      formation of diffuse cell networks, whereas disruption of cable pilus biogenesis
      enhanced autoaggregation and the formation of compact cell aggregates.
      Autoaggregation was observed both in culture and during B. cenocepacia infection
      of A549 epithelial cell monolayers. These findings indicate that cable pilus
      expression plays an important role in mediating B. cenocepacia cell-cell
      interactions, and that both cable pilus-dependent and cable pilus-independent
      mechanisms may contribute to B. cenocepacia adherence to cellular and acellular
      surfaces.

PMID- 14638437
TI  - A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear
      cells present in the decidua additively to membrane-bound HLA-G1.
AB  - PROBLEM: Our previous studies have demonstrated that a subclass of soluble human
      leukocyte antigen-G1 protein (sub-sHLA-G1), that has alpha1 to alpha3 extra
      cellular portion but lacks C-terminus of authentic soluble HLA-G1 secreted by
      trophoblasts, fine-tunes the release of cytokines from peripheral blood
      mononuclear cells (PBMCs) chiefly by counterbalancing membrane-bound HLA-G1 (mHLA
      G1), and thereby may play a role in maintaining pregnancy. In this study, we
      investigated whether the presence of sHLA-G1 protein altered the release of
      cytokines from decidual mononuclear cells (DMCs) which are localized at the
      interface of feto-maternal interaction and whose cell population is completely
      different from PBMCs. METHOD OF STUDY: We cultured peripheral DMCs with either
      HLA-A and -B lacking B lymphoblast cell line (721.221 cells) or the cells
      transfected with mHLA-G1 (721.221-G1 cells) with or without sub-sHLA-G1.
      Cytokines concentrations in the culture media were determined by an enzyme-linked
      immunosorbent assay. RESULTS: Regardless of the presence of mHLA-G1 expressing
      cells, the addition of the recombinant sub-sHLA-G1 protein in the DMC culture
      media decreased the amounts of tumor necrosis factor (TNF)-alpha and interferon
      (IFN)-gamma, with the release of IL-4 from DMCs being unchanged. CONCLUSION: The
      sub-sHLA-G1 protein modulates the release of cytokines from DMCs additively to
      mHLA-G1 expressing cells. In view of the distinct fetomaternal interaction during
      implantation, it appears that sHLA-G1 might play a role in the establishment of
      pregnancy by regulating cytokine release in concert with mHLA-G1.

PMID- 14638438
TI  - Human seminal plasma prolactin-inducible protein is an immunoglobulin G-binding
      protein.
AB  - Antisperm antibodies (ASA) are present in 20% of couples seeking treatment for
      infertility. Antibody-binding proteins in seminal plasma may protect sperm from
      ASA-induced damage. We have previously isolated several IgG-binding proteins from
      human seminal plasma using IgG affinity chromatography. Here, we report another
      such protein which we have identified by amino acid sequencing and confirmed by
      western blotting to be prolactin-inducible protein (PIP). PIP binds via the Fc
      fragment of IgG. We have determined the level of PIP in normal seminal plasma to
      be 3.4 mg/ml (interquartile range 2.0-4.4 mg/ml). We have found there is no
      difference in the mean level of PIP in seminal plasma from fertile or infertile
      men regardless of ASA status. PIP was shown to exist in several isoforms in
      seminal plasma by Western blot. There is a complex pattern of PIP isoform
      variability in seminal plasma from fertile and infertile men but one multimeric
      form of PIP was absent from the seminal plasma of men with ASA who were fertile.
      This may reflect consumption of PIP in these men. The physiological function of
      PIP remains unknown, but the ability of PIP to bind IgG-Fc suggests PIP may have
      an immunomodulatory role.

PMID- 14638439
TI  - Activated peripheral blood mononuclear cells induce p44/42 mitogen-activated
      protein kinase phosphorylation in trophoblast-like JAR cells.
AB  - Mammalian pregnancy bears many similarities to transplantation, since the fetus
      is semi-allogenic to mother. Thus, mammals have developed numerous mechanisms to
      protect the developing fetus from maternal immunologic recognition and attack. We
      have previously shown that human choriocarcinoma JAR cells, which resemble first
      trimester trophoblasts, regulate several important mRNAs in activated peripheral
      blood mononuclear cells (PBMC). We now provide further evidence that
      communication between maternal and fetal tissues is bi-directional, and that
      activation of PBMC leads to activation of specific signaling pathways in JAR
      cells. Activated PBMC were co-cultured with JAR cells for specific time
      intervals, after which JAR cells were lysed and subjected to western blotting for
      activated forms of the JNK, Erk 1-2, and p38 mitogen-activated protein kinases
      (MAPK). Phosphorylation of Erk 1-2, but not JNK or p38, was induced in co
      cultures of PBMC and JAR cells. These results were also obtained when JAR cells
      were incubated with conditioned medium from activated, but not resting, PBMC.
      Results were confirmed using specific MAPK reporter constructs, using luciferase
      activity as a measure of Elk-1 phosphorylation. Erk 1-2 phosphorylation was not
      required for JAR cells to inhibit IL-2 production in activated PBMC. Addition of
      the specific MAPK inhibitor UO126 to JAR cells prior to the addition of activated
      PBMC to the cultures did not abolish the capacity of JAR cells to inhibit IL-2
      mRNA expression in PBMC. We conclude that there is likely to be significant bi
      directional signaling between leukocytes and trophoblasts at the maternal-fetal
      interface. We propose the existence of a delicate maternal-fetal immunologic
      homeostasis based on these experimental results.

PMID- 14638440
TI  - Gene fusion of molecular adjuvant C3d to hCGbeta enhances the anti-hCGbeta
      antibody response in DNA immunization.
AB  - OBJECTIVE: To express the hCGbeta-C3d3 fusion protein in a CHO cell continual
      expression system to investigate further the adjuvant effects of C3d on
      contraceptive vaccination. METHOD: We constructed a plasmid pcDNA3-hCGbeta-C3d3
      which contains three copies of murine C3d cDNA and the hCGbeta gene by cloning
      the chimerical hCGbeta-C3d3 cDNA into the eukaryotic vector pcDNA3 downstream of
      the CMV promoter. The plasmid was transfected into a COS-7 cell transient
      expression system and a CHO cell continual expression system. RIA was used to
      detect hCGbeta in the culture supernatant. Western blot and Raji cell
      immunohistochemical assays were performed to evaluate the expressed protein.
      Then, 6-8-week-old female BALB/c mice were inoculated intramuscularly with pcDNA3
      hCGbeta and pcDNA3-hCGbeta-C3d3, and ELISA was used to assess anti-hCGbeta IgG
      antibody in serum. RESULTS: In 72 h after COS-7 cells were transfected with the
      plasmid pcDNA3-hCGbeta-C3d3, 1.0x10(5) cells could secrete 152 ng of the
      recombinant protein (calculated by hCGbeta contained). The transfected CHO cells,
      which were then screened by G418, could continuously secrete the fusion protein
      at 660 ng/10(6) cells/48 h. The hCGbeta-C3d3 protein was purified by anti-hCGbeta
      immunoaffinity chromatography. Raji cell immunohistochemical assay demonstrated
      that both the hCGbeta and C3d3 were successfully fused. After DNA immunization
      intramuscularly, the anti-hCGbeta IgG antibody titer in the pcDNA3-hCGbeta-C3d3
      immunized group was 243-fold higher than that of the pcDNA3-hCGbeta immunized
      group. CONCLUSION: We have expressed the hCGbeta-C3d3 protein successfully, both
      in a transient expression system (COS-7 cells) and in a stable expression system
      (CHO cells). The C3d3 molecular adjuvant can enhance significantly the
      immunogenecity of hCGbeta antigen in DNA immunization.

PMID- 14638441
TI  - Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune
      orchitis.
AB  - Experimental autoimmune orchitis (EAO) is characterized by an interstitial
      mononuclear cell infiltrate and a severe lesion of seminiferous tubules with germ
      cells that undergo apoptosis and sloughing. The mechanism by which immune cells
      migrate and extravasate in the testicular interstitium is poorly understood. The
      aim of this study was to detect the variations in the expression of monocyte
      chemoattractant protein-1 (MCP-1/CCL2) and its receptor in the testis of rats
      undergoing autoimmune orchitis. EAO was induced in Sprague-Dawley adult rats by
      active immunization with an emulsion of testicular homogenate and complete Freund
      adjuvant using Bordetella pertussis as co-adjuvant. Control rats injected with
      saline and adjuvants and normal untreated rats were also studied. By ELISA we
      observed a significant increase of MCP-1 in the testicular fluid (TF) and in the
      conditioned medium obtained from cultures of testicular macrophages of rats with
      EAO compared with control groups. By immunohistochemistry, an increase in MCP-1
      expression was observed in mononuclear, endothelial, Leydig and peritubular
      cells. MCP-1 immunoreactivity was also detected in Sertoli cell cytoplasm of rats
      with severe orchitis. A 2-fold increase in the number of mononuclear cells that
      express CCR2 was also found in rats with orchitis compared with controls. In
      conclusion, we demonstrated in vivo that MCP-1 is highly expressed in testicular
      interstitial cells suggesting that this chemokine has an important role in
      recruiting immune cells to the testis in rats undergoing autoimmune orchitis.

PMID- 14638442
TI  - Physiological changes of Fas expression in peripheral lymphocyte subsets during
      the menstrual cycle.
AB  - We have examined changes in peripheral lymphocyte subsets, and Fas expression in
      these subsets, during the menstrual cycle. Measurements were made by three-color
      flow cytometry in the follicular and luteal phases of the menstrual cycle in ten
      healthy women. The numbers of leukocytes, granulocytes and monocytes were
      significantly higher in the luteal phase than the follicular phase. The
      percentage of CD8(+) cells was greater in the luteal phase than the follicular
      phase. The percentages of Fas(+) cells among T cells and NK cells were higher in
      the luteal phase than the follicular phase. These findings suggest that the
      menstrual cycle affects leukocytes, lymphocyte subsets, and Fas expression in
      these subsets, and that changes in the luteal phase of the menstrual cycle are
      similar to those in pregnancy.

PMID- 14638443
TI  - Guidelines for reporting information in studies of diagnostic test accuracy: the
      STARD initiative.

PMID- 14638444
TI  - My unexpected life.

PMID- 14638445
TI  - Diagnosing tests: using and misusing diagnostic and screening tests.
AB  - Tests can be used either diagnostically (i.e., to confirm or rule out the
      presence of a condition in people suspected of having it) or as a screening
      instrument (determining who in a large group of people has the condition and
      often when those people are unaware of it or unwilling to admit to it). Tests
      that may be useful and accurate for diagnosis may actually do more harm than good
      when used as a screening instrument. The reason is that the proportion of false
      negatives may be high when the prevalence is high, and the proportion of false
      positives tends to be high when the prevalence of the condition is low (the usual
      situation with screening tests). My first aim of this article is to discuss the
      effects of the base rate, or prevalence, of a disorder on the accuracy of test
      results. My second aim is to review some of the many diagnostic efficiency
      statistics that can be derived from a 2 x 2 table, including the overall correct
      classification rate, kappa, phi, the odds ratio, positive and negative predictive
      power and some variants of them, and likelihood ratios. In the last part of this
      article, I review the recent Standards for Reporting of Diagnostic Accuracy
      guidelines (Bossuyt et al., 2003) for reporting the results of diagnostic tests
      and extend them to cover the types of tests used by psychologists.

PMID- 14638446
TI  - Standardizing DSM-IV diagnoses: the clinical applications of structured
      interviews.
AB  - Psychological assessments of Axis I and Axis II diagnoses are strongly enhanced
      by the use of structured interviews. Structured interviews standardize the
      clinical inquiries, sequencing of diagnostic issues, and criterion-based ratings.
      For a broad range of clinical settings, structured interviews can systematically
      assess changes in patient status, corroborative data from multiple sources,
      interrater and test-retest reliability, and diagnostic validity. This article
      outlines the potential uses of different diagnostic interviews that are tailored
      for or adapted to specific clinical purposes.

PMID- 14638447
TI  - NEO PI-R predictors of alcohol use and alcohol-related problems.
AB  - We investigated the relationships between Five-factor model domains and facets
      and drinking and alcohol-related problems. We also examined the moderating
      effects of gender. Two hundred students (99 men and 101 women) who had used
      alcohol in the past year completed self-report and interview assessments.
      Bivariate analyses demonstrated some significant relationships. In the
      multivariate analyses that controlled for gender, Neuroticism and
      Conscientiousness were linked to drinking, but only some of the facets from these
      domains had significant relationships to drinking. Facets of Extraversion and
      Agreeableness, but not these domains, were associated with drinking. Neuroticism
      and Conscientiousness and most of their facets were related to alcohol-related
      problems in the multivariate analyses. The interactions between gender and traits
      were not significant.

PMID- 14638448
TI  - Exploring the psychometric properties and construct validity of the MCMI-III
      anxiety and avoidant personality scales.
AB  - The Millon Clinical Multiaxial Inventory (MCMI; Millon, 1983) is a commonly used
      self-report instrument designed to aid in the assessment of Axis I and Axis II
      disorders. Concerns have been expressed regarding the procedures used in the
      normative research for the current version of the MCMI (MCMI-III; Millon, 1994)
      leading to a call for additional validity research on the MCMI-III (Retzlaff,
      1996). In this study, we investigated the psychometric properties of the MCMI
      III's Anxiety and Avoidant personality scales in a sample of patients diagnosed
      with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
      Psychiatric Association, 1994) anxiety disorders. Our results suggest that the
      MCMI-III Avoidant scale is reliable (r =.89) and it was found to demonstrate
      appropriate convergent and divergent validity with other self-report measures.
      The MCMI-III Anxiety scale also showed adequate reliability (r =.78); however,
      our findings raise some concerns about the discriminant validity of this scale. A
      scale composed of the MCMI-III core anxiety items was found to have better
      discriminant validity. These findings are consistent with those reported by other
      researchers regarding the relationship between self-report measures of anxiety,
      avoidance, and depression. We conclude that the MCMI-III measures of anxiety and
      avoidance are consistent with other measures of these constructs and may provide
      valuable clinical information in this regard.

PMID- 14638449
TI  - Depression and vulnerability as assessed by the Rorschach method.
AB  - We examined clinically depressed (CD; n = 16), previously depressed (PD; n = 19)
      and never depressed (ND; n = 18) individuals on 13 theoretically selected
      Rorschach (Exner, 1993; Rorschach, 1942) variables and on the Beck Depression
      Inventory (BDI; Beck, Rush, Shaw, & Emery, 1979). The group assignment was made
      according to the criteria of Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; American Psychiatric Association, 1994). We tested 2
      contradictory models for depressive vulnerability, Beck's (Clark & Beck, 1999)
      and Miranda and Persons's (1988; Persons & Miranda, 1992), in a planned
      comparison design with focused contrasts. The CDs significantly contrasted the
      combined group of NDs and the PDs in a pathological direction on 8 of the 13
      Rorschach variables and on the BDI. However, the combined group of CDs and PDs
      also significantly contrasted the NDs in a pathological direction on 3 of these
      Rorschach variables and on the BDI. In addition, logistic regression analyses
      indicated that Rorschach indexes significantly improved the prediction of major
      depression above and beyond that achieved by the BDI. The findings show that the
      Rorschach method was able to identify (a) cognitive and aggressive disturbances
      that are present in individuals who are actively depressed but not in individuals
      who have been depressed in the past or never been depressed and (b) affective and
      coping disturbances that are present in depressed individuals and to some degree
      in PD individuals but not in individuals who have not experienced depression. We
      discuss the scanty evidence of psychological disturbances in PD individuals, as
      measured with the Rorschach, in relation to the mood-state dependent hypothesis
      of Miranda and Persons (1988; Persons & Miranda, 1992).

PMID- 14638450
TI  - Factor structure of the private self-consciousness scale: role of item wording.
AB  - In 3 studies, I have tested the structure of different phrasing versions of the
      Private Self-Consciousness Scale (PrSC; Fenigstein, Scheier, & Buss, 1975) using
      exploratory and confirmatory factor-analytic methods and examined their
      predictive validity. For the original version of the PrSC, a 2-factorial model
      similar to Nystedt and Ljungberg's (2002) solution was found to best fit the
      data. When all scale items included extreme rate of occurrence words such as
      always, a single-factor solution emerged. Finally, when all words reflecting rate
      of occurrence were removed, again a 2-factor structure emerged, although
      different in item composition from that of the original version. In addition,
      different patterns of association emerged between the PrSC factors and depression
      and self-esteem for the extreme and neutral versions. I discuss the importance of
      reconceptualizing self-consciousness and the need for a new, theoretically based
      scale for self-consciousness.

PMID- 14638451
TI  - Confirmatory factor analysis of the multidimensional scale of perceived social
      support in clinically distressed and student samples.
AB  - Previous authors (e.g., B. R. Sarason, Shearin, Pierce, & Sarason, 1987) have
      found that perceived social support can affect the emotional well-being of an
      individual. Consequently, the effective assessment of social supports is a key
      issue in both research and clinical practice. The Multidimensional Scale of
      Perceived Social Support (MSPSS; Zimet, Dahlem, Zimet, & Farley, 1988) divides
      perceived social support into 3 distinct constructs-that derived from Family
      members, from Friends, and from Significant Others. This study is the first to
      assess the MSPSS using confirmatory factor analysis in both a college student (N
      = 549) and psychiatric outpatient (N = 156) sample. Based on several goodness-of
      fit indicators, a 3-factor model for the MSPSS was supported in both samples, as
      was a single, higher order domain of Global social support. The perceived social
      support factors of Family and Friends consistently had the strongest associations
      with symptomatology. These results support the use of the MSPSS as a brief
      instrument for assessing the hierarchical structure of perceived social support
      in a variety of samples.

PMID- 14638452
TI  - Exploring issues of personality measurement and structure through the development
      of a short form of the Eysenck Personality Profiler .
AB  - In this article, we develop a revised short form of the original Eysenck
      Personality Profiler (EPP; H. J. Eysenck & Wilson, 1991). In addition, we address
      topics of broad theoretical importance such as the recurrent empirical finding of
      correlations between conceptually orthogonal personality dimensions and the
      possibility that gender differences in these dimensions are partly spurious. In
      Study 1 (N = 227), we demonstrate that the existing short form of the EPP (EPP
      SF; H. J. Eysenck, Wilson, & Jackson, 1996) provides a poor fit to the data and
      we develop a revised well-fitting version. In Study 2, we retest this version on
      an independent new sample (N = 3,374) where it is again found to fit the data
      well. We show that most of the structural and measurement parameters of the
      revised EPP-SF are invariant across genders. Structured means analysis indicated
      a significant gender difference in Psychoticism, with men scoring higher than
      women, but no differences in Extraversion or Neuroticism. Our discussion focuses
      on issues concerning personality measurement and structure, including an
      examination of the role of confirmatory factor analysis in personality research.

PMID- 14638453
TI  - Assessing Axis I symptomatology on the SADS-C in two correctional samples: the
      validation of subscales and a screen for malingered presentations.
AB  - The Schedule of Affective Disorders and Schizophrenia-Change Version (SADS-C;
      Spitzer & Endicott, 1978b) is a brief, highly reliable structured interview with
      clinical applications to diverse populations. This investigation involved
      reanalyses of data from 2 earlier studies (Rogers, Grandjean, Tillbrook, Vitacco,
      & Sewell, 2001; Ustad, Rogers, & Salekin, 1998). Focusing on 2 clinical samples
      from a metropolitan jail, we investigated its subscales via exploratory and
      confirmatory factor analysis. A good model fit was found (comparative fit index
      =.92; robust comparative fit index =.94) for 4 subscales (Dysphoria, Psychosis,
      Mania, and Insomnia) with good interrater reliability (M intraclass coefficient
      =.95) and clinical relevance. As a preliminary screen for feigned mental
      disorders, 2 detection scales (Symptom Combinations and Symptom Selectivity) were
      moderately successful. By maximizing negative predictive power, the SADS-C
      detection strategies proved effective at ruling out feigning for mentally
      disordered offenders with a high likelihood of genuine disorders.

PMID- 14638454
TI  - Further psychometric support for the Sensation Seeking Scale--Form V.
AB  - In this study, we investigated the psychometric properties of the Sensation
      Seeking Scale-V (SSS-V; Zuckerman, Eysenck, & Eysenck, 1978). Participants were
      498 undergraduate students at a public university. A confirmatory factor analysis
      supported the SSS-V four-factor structure. In addition, the internal consistency
      was high and the convergent validity of the SSS-V was supported. These findings
      replicate research supporting the construct validity and reliability of the SSS-V
      in a nonclinical college sample.

PMID- 14638455
TI  - Mechanisms of microgravity induced orthostatic intolerance: implications for
      effective countermeasures.
AB  - The development of orthostatic hypotension and instability immediately after
      return from spaceflight has been a significant operational problem to astronauts
      for more than four decades. Significant reductions in stroke volume and
      peripheral vascular resistance contribute to ineffective maintenance of systemic
      arterial blood pressure during standing after spaceflight despite compensatory
      elevations in heart rate. The primary mechanism underlying reduced stroke volume
      appears to be a reduction in preload associated with reduced circulating blood
      volume, although cardiac atrophy might also contribute. Space flight and ground
      based experiments have demonstrated that an inability to provide adequate
      peripheral vasoconstriction in astronauts that become presyncopal may be
      associated with several mechanisms including reduced sympathetic nerve activity,
      arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta
      adrenergic receptors, etc. In addition, an inability to provide adequate
      tachycardia in presyncopal subjects may be associated with reduced carotid
      cardiac baroreflex sensitivity. Based on the current knowledge and understanding
      of cardiovascular mechanisms that are altered during exposure to microgravity, a
      major focus of future research should be directed to the systematic evaluation of
      potential countermeasures that specifically target and restore the function of
      these mechanisms. Based on a preliminary systematic evaluation presented in this
      review, acute physical exercise designed to elicit maximal effort, G-suit
      inflation, artificial gravity, and specific pharmacological interventions, alone
      or in combination, have shown promise as successful countermeasures that provide
      protection against post-flight orthostatic intolerance.

PMID- 14638456
TI  - Hypergravity-induced immunomodulation in a rodent model: lymphocytes and lymphoid
      organs.
AB  - The major goal of this study was to quantify changes in lymphoid organs and cells
      over time due to centrifugation-induced hypergravity. C57BL/6 mice were exposed
      to 1, 2 and 3 G and the following assays were performed on days 1, 4, 7, 10, and
      21: spleen, thymus, lung, and liver masses; total leukocyte, lymphocyte,
      monocyte/macrophage, and granulocyte counts; level of splenocyte apoptosis;
      enumeration of CD3+ T, CD3+/CD4+ T helper, CD3+/CD8+ T cytotoxic, B220+ B, and
      NK1.1+ natural killer cells; and quantification of cells expressing CD25, CD69,
      and CD71 activation markers. The data show that increased gravity resulted in
      decreased body, spleen, thymus, and liver, but not lung, mass. Significant
      reductions were noted in all three major leukocyte populations (lymphocytes,
      granulocytes, monocyte/macrophages) [correction of macrphages] with increased
      gravity; persistent depletion was noted in blood but not spleen. Among the
      various lymphocyte populations, the CD3+/CD8+ T cells and B220+ B cells were the
      most affected and NK1.1+ NK cells the least affected. Overall, the changes were
      most evident during the first week, with a greater influence noted for cells in
      the spleen. A linear relationship was found between some of the measurements and
      the level of gravity, especially on day 4. These findings indicate that
      hypergravity profoundly alters leukocyte number and distribution in a mammalian
      model and that some aberrations persisted throughout the three weeks of the
      study. In certain cases, the detected changes were similar to those observed
      after whole-body irradiation. In future investigations we hope to combine
      hypergravity with low-dose rate irradiation and immune challenge.

PMID- 14638457
TI  - Short-term hypergravity influences NGF and BDNF expression, and mast cell
      distribution in the lungs and heart of adult male mice.
AB  - In this study we investigate the effects of short-term hypergravity on lung and
      heart neurotrophins and mast cell distribution. Our results showed that brain
      derived-neurotrophic factor (BDNF) protein and mRNA expression are increased in
      the lungs of mice exposed to hypergravity while in the heart hypergravity causes
      a marked reduction in BDNF mRNA expression, and a decrease in BDNF protein.
      Compared to controls, nerve growth factor (NGF) protein was expressed more in the
      heart of rotated mice. These observations demonstrate that altered hypergravity
      can affect, though differentially, the local expression of NGF and BDNF proteins
      and their mRNAs in the lung and heart and indicates that short-term exposure to
      hypergravity causes a marked increase in BDNF, but not in NGF in the lungs of
      adult mice. Moreover, mast cells, which are NGF-producing cells and implicated in
      cardiac and respiratory activity, increased in number in proximity to blood
      vessels in the heart and in lung airway epithelium of rotated mice. This study
      indicates that hypergravity influences cardiovascular and respiratory tissue and
      suggests a neurotrophin involvement in the reaction to this environmental
      exposure.

PMID- 14638458
TI  - Succinate dehydrogenase activity in rat dorsolateral ventral horn motoneurons at
      L6 after spaceflight and recovery.
AB  - Succinate dehydrogenase (SDH) activity levels of motoneurons in the rostral,
      middle, and caudal portions of the dorsolateral region of the ventral horn of the
      6th lumbar (L6) segment of the rat spinal cord were determined after 14 days of
      spaceflight and after 9 days of recovery on Earth. The mean SDH activity of
      motoneurons with cell body sizes between 500 and 800 micrometers2 located in the
      rostral portion of the L6 segment was lower in spaceflight than in age-matched
      control rats. The decrease in motoneuron SDH activity persisted for at least 9
      days of recovery on Earth. In contrast, the mean SDH activity of motoneurons
      located in the middle and caudal portions of the L6 segment were unaffected by
      spaceflight and recovery on Earth. The motoneurons in the rostral portion of the
      L6 segment presumably innervate both high- and low-oxidative fibers in hindlimb
      muscles, whereas those in the middle and caudal portions presumably innervate
      perineal muscles that are comprised only of low-oxidative fibers. These data
      indicate that moderate-sized motoneurons, most likely innervating fibers in high
      oxidative muscles, are responsive to the microgravity environment.

PMID- 14638459
TI  - Effects of nine weeks of unloading on neuromuscular activities in adult rats.
AB  - Effects of 9-week hindlimb suspension and 8-week recovery on locomotor
      performance and electromyogram (EMG) activities of soleus (Sol), plantaris (Pl),
      lateral gastrocnemius (LG), and tibialis anterior (TA), were studied in adult
      rats. Hyperextension of knee and ankle joints, noted after nine weeks of
      suspension, did not recover during 8-week ambulation. Growth of Sol was fully
      inhibited by suspension and did not recover completely within 8 weeks of
      ambulation. The EMG levels in Sol, Pl, and LG 1 day after suspension were 52-76%
      less than the pre-suspension level (resting on the floor). These activities were
      recovered to or near the pre-suspension level around 1 week, but decreased again
      to 10-29% of controls from 7 to 9 weeks. The integrated EMG of TA was elevated
      during the first week of suspension but then gradually declined to control levels
      within four weeks. At the end of suspension, the Sol and Pl, not the LG, EMGs
      remained reduced and the TA EMG remained hyperactive. Co-activation of dorsi- and
      plantar- flexors occurred often during quadripedal walking following suspension.
      Such a phenomenon was not observed in the control rats. These phenomena were
      recovered within 1 week. It is suggested that the unloading-related alterations
      of neuromuscular activities and/or locomotion, but not the hyperextension of knee
      and ankle joints, in rats are reversible.

PMID- 14638460
TI  - Alteration of gene expression profiles in skeletal muscle of rats exposed to
      microgravity during a spaceflight.
AB  - To clarify the mechanism of skeletal muscle wasting during spaceflights, we
      investigated whether intramuscular gene expression profiles are affected, by
      using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab
      spaceflight were sacrificed 24 hours after return to earth (MG group). Ground
      control rats were maintained for 17 days in flight-simulated cages (CS group).
      Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius
      muscle mass, respectively, as compared to ground controls. Muscle RNA was
      analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS
      pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations
      in gene expression were verified for selected genes by reverse-transcription PCR.
      In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold,
      and 38 were down-regulated compared to controls. There was inhibition of genes
      for cell proliferation and growth factor cascades, including cell cycle genes and
      signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins
      G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data
      indicate that following exposure to microgravity, there is downregulation of
      genes involved in regulation of muscle satellite cell replication.

PMID- 14638461
TI  - Type 1 vs. type 2 cytokine secretion in vitro and its regulation by
      hydrocortisone in humans subjected to 120-day anti-orthostatic bed-rest regime.
AB  - Head-Down Bed-Rest (HDBR) mimics some of the physiological stress effects of
      microgravity. Six healthy volunteers were subjected to bed-rest for 120 days.
      Blood samples were collected one month before (PRE), on day 110 of HDBR (DAY
      110), and on the 7th day after bed-rest regime ends (POST). Distribution of T
      cell subsets, NK-, B-cells and monocytes was assessed in the whole blood.
      Distribution of cytokine secreting T-cells was assessed in PMA/ionomycin cell
      culture. Peripheral Blood Mononuclear Cells (PBMC) and whole blood cells (WB)
      were activated with a combination of PHA and LPS to assess cytokine secretion. In
      addition, PHA/LPS activated cell cultures were treated with 10(-6) M of
      hydrocortisone (HCS) in order to study stress-induced alterations in the cortisol
      sensitivity of immunocytes. Results from HCS culture were compared to non-treated
      control cultures. Stress factors of HDBR affect immune responsiveness and immune
      endocrine homeostatic interrelations in vitro as follow: 1) alter expression of
      surface receptor to IL-2 (CD25) by CD4+ and CD8+ T-cell subsets in PHA/LPS
      activated PBMC culture; 2) alter distribution of IL-2 and/or IFN-gamma producing
      CD4+ and CD8+ T-cells in PMA/ionomycin activated culture; 3) significantly affect
      secretion of IL-2, IFN-gamma, and IL-4, but not IL-10 and soluble IL-2 receptor
      alpha in PHA/LPS activated PBMC culture; 4) shift Type 1 vs. Type 2 cytokine
      balance in PHA/LPS activated culture toward to Type 1 response; 5) in vitro
      treatment with hydrocortisone unequally modulate expression of CD25 on CD4+, and
      CD8+ T-cells, as well as secretion of Type 1 and Type 2 cytokines in PHA/LPS
      activated PBMC culture during bed-rest regime; 6) assessment of immune profile
      depends from the cellular and humoral milieu of cell culture.

PMID- 14638462
TI  - An infrared system for monitoring Drosophila motility during microgravity.
AB  - Presently, the precise mechanisms of the aging process are unknown. Examination
      and comprehension of the aging process in other species could lead to significant
      advances in the understanding of human aging. Drosophila melanogaster (fruit
      fly), commonly used for aging studies, is a widely studied organism in terms of
      behavior, development, and genetics. Previous microgravity experiments have shown
      a significant decrease in the life span of young male Drosophila after
      microgravity exposure. This decrease in lifespan may be related to locomotor
      activity, a convenient measure of overall physiological performance. This study
      describes the design and performance of a Drosophila Infrared Motility Monitoring
      System (DIMMS). The DIMMS uses a unique design of two infrared (IR) beams per fly
      to measure the locomotor activity of 240 flies. Locomotor activity is measured in
      terms of number of IR crossings per unit time, instantaneous velocity, and
      continuous velocity. Ground-based results using the DIMMS equipment agree well
      with previous values for Drosophila locomotor velocity. DIMMS is an improvement
      over equipment previously used due to its ability to continuously monitor
      locomotor activity throughout short-duration microgravity exposure. DIMMS is also
      lightweight, compact, and power efficient. DIMMS has been flight tested onboard
      NASA's KC-135 reduced gravity research aircraft and a Nike-Orion sounding rocket.

PMID- 14638463
TI  - Compression under a mechanical counter pressure space suit glove.
AB  - BACKGROUND: Current gas-pressurized space suits are bulky stiff shells severely
      limiting astronaut function and capability. A mechanical counter pressure (MCP)
      space suit in the form of a tight elastic garment could dramatically improve
      extravehicular activity (EVA) dexterity, but also be advantageous in safety,
      cost, mass and volume. The purpose of this study was to verify that a prototype
      MCP glove exerts the design compression of 200 mmHg, a pressure similar to the
      current NASA EVA suit. METHODS: Seven male subjects donned a pressure measurement
      array and MCP glove on the right hand, which was placed into a partial vacuum
      chamber. Average compression was recorded on the palm, the bottom of the middle
      finger, the top of the middle finger and the dorsum of the hand at pressures of
      760 (ambient), 660 and 580 mmHg. The vacuum chamber was used to simulate the
      pressure difference between the low breathing pressure of the current NASA space
      suits (approximately 200 mmHg) and an unprotected hand in space. RESULTS: At
      ambient conditions, the MCP glove compressed the dorsum of the hand at 203.5 +/-
      22.7 mmHg, the bottom of the middle finger at 179.4 +/- 16.0 mmHg, and the top of
      the middle finger at 183.8 +/- 22.6 mmHg. The palm compression was significantly
      lower (59.6 +/- 18.8 mmHg, p<0.001). There was no significant change in glove
      compression with the chamber pressure reductions. CONCLUSIONS: The MCP glove
      compressed the dorsum of the hand and middle finger at the design pressure.

PMID- 14638464
TI  - Ribosomal protection proteins and their mechanism of tetracycline resistance.

PMID- 14638465
TI  - Improved green fluorescent protein reporter gene-based microplate screening for
      antituberculosis compounds by utilizing an acetamidase promoter.
AB  - The green fluorescent protein (GFP) gene offers many advantages as a viability
      reporter for high-throughput antimicrobial drug screening. However, screening for
      antituberculosis compounds by using GFP driven by the heat shock promoter, hsp60,
      has been of limited utility due to the low signal-to-noise ratio. Therefore, an
      alternative promoter was evaluated for its enhanced fluorescence during
      microplate-based culture and its response to 18 established antimicrobial agents
      by using a green fluorescent protein microplate assay (GFPMA). Mycobacterium
      tuberculosis strains H37Rv, H37Ra, and Erdman were transformed with pFPCA1, which
      contains a red-shifted gfp gene driven by the acetamidase promoter of M.
      smegmatis mc(2)155. The pFPCA1 transformants achieved higher levels of GFP
      mediated fluorescence than those carrying the hsp60 construct, with signal-to
      noise ratios of 20.6 to 27.8 and 3.8 to 4.5, respectively. The MICs of 18
      established antimicrobial agents for all strains carrying pFPCA1 in the GFPMA
      were within 1 to 2 twofold dilutions of those determined by either the
      fluorometric or the visual microplate Alamar Blue assay (MABA). No significant
      differences in MICs were observed between wild-type and pFPCA1 transformants by
      MABA. The optimized GFPMA is sufficiently simple, robust, and inexpensive (no
      reagent costs) to be used for routine high-throughput screening for
      antituberculosis compounds.

PMID- 14638466
TI  - Treatment of intra-abdominal abscesses caused by Candida albicans with antifungal
      agents and recombinant murine granulocyte colony-stimulating factor.
AB  - The aim of the present study was to assess the influence of immunomodulation of
      host defense with recombinant murine granulocyte colony-stimulating factor (rmG
      CSF) on intra-abdominal abscesses caused by Candida albicans. Mice received
      prophylaxis or therapy with 1 microg of rmG-CSF/day in the presence or absence of
      antifungal treatment consisting of amphotericin B (0.75 mg/kg of body weight/day)
      or fluconazole (50 mg/kg/day). The number of Candida CFU in abscesses was
      significantly reduced (P<0.05) in mice receiving rmG-CSF prophylaxis (day -1 or
      day -1 through 2) compared with controls on day 8 of infection. Administration of
      rmG-CSF therapy alone (for 5 days starting on day 4 of infection) had no
      influence on the number of Candida CFU in abscesses. Amphotericin B treatment was
      significantly more effective than fluconazole treatment (3.41 log CFU/abscesses;
      95% confidence interval [CI], 3.17 log CFU/abscesses; 3.65 versus 3.90 log
      CFU/abscesses; 95% CI, 3.66 log CFU/abscesses, 4.16 log CFU/abscesses; P<0.05).
      Therapeutic administration of rmG-CSF in conjunction with an antifungal agent
      showed a tendency towards a further reduction of Candida CFU in abscesses than
      antifungal treatment only. In conclusion, in this experimental model of intra
      abdominal Candida abscesses, rmG-CSF administration did not have a detrimental
      influence on the course of infection. Amphotericin B treatment was most
      effective, and additional rmG-CSF therapy did not antagonize the effect of
      antifungal treatment. In contrast, addition of rmG-CSF therapy to antifungal
      treatment might further enhance the beneficial effect of the antifungal agent.

PMID- 14638467
TI  - Effects of DQ-113, a new quinolone, against methicillin- and vancomycin-resistant
      Staphylococcus aureus-caused hematogenous pulmonary infections in mice.
AB  - We compared the effects of DQ-113, a new quinolone, to those of vancomycin (VCM)
      and teicoplanin (TEIC) in murine models of hematogenous pulmonary infections
      caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive
      S. aureus (VISA). The MICs of DQ-113, VCM, and TEIC for MRSA were 0.125, 1.0, and
      0.5 microg/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0
      microg/ml, respectively. Treatment with DQ-113 resulted in a significant decrease
      in the number of viable bacteria in the lungs of the mice used in the MRSA
      infection model (counts in mice treated with DQ-113, VCM, and TEIC and control
      mice, 6.33 +/- 0.22, 7.99 +/- 0.14, 7.36 +/- 0.20, and 8.47 +/- 0.22 log10
      CFU/lung [mean +/- standard error of the mean], respectively [P<0.01 for the
      group treated with DQ-113 compared with the group treated with VCM or TEIC or the
      untreated group]). Mice infected with VISA were pretreated with cyclophosphamide,
      and the survival rate was recorded daily for 10 days. At the end of this period,
      90% of the DQ-113-treated mice were still alive, whereas only 45 to 55% of the
      mice in the other three groups were still alive (P<0.05 for the group treated
      with DQ-113 compared with the group treated with VCM or TEIC or the untreated
      group]). DQ-113 also significantly (P<0.05) reduced the number of viable bacteria
      in the lungs compared with those in the lungs of the other three groups (counts
      in mice treated with DQ-113, VCM, and TEIC and control mice, 5.76 +/- 0.39, 7.33
      +/- 0.07, 6.90 +/- 0.21, and 7.44 +/- 0.17 log10 CFU/lung, respectively).
      Histopathological examination revealed milder inflammatory changes in DQ-113
      treated mice than in the mice in the other groups. Of the antibiotics analyzed,
      the parameters of area under the concentration-time from 0 to 6 h (AUC(0-6))/MIC
      and the time that the AUC(0-6) exceeded the MIC were the highest for DQ-113. Our
      results suggest that DQ-113 is potent and effective for the treatment of
      hematogenous pulmonary infections caused by MRSA and VISA strains.

PMID- 14638468
TI  - In vivo efficacy of a new quinolone, DQ-113, against Streptococcus pneumoniae in
      a mouse model.
AB  - DQ-113 is a new quinolone with potent activity against gram-positive pathogens.
      The in vivo activity of DQ-113 against Streptococcus pneumoniae was compared with
      those of gatifloxacin and ciprofloxacin in a mouse model. For this purpose, two
      strains of S. pneumoniae were used: penicillin-susceptible S. pneumoniae (PSSP)
      and penicillin-resistant S. pneumoniae (PRSP). The survival rates of mice
      infected with PSSP and PRSP at 14 days after infection were 80% in the DQ-113
      treated group and 0 to 10% in the other three groups. In murine infections caused
      by PSSP, the 50% effective doses (ED50s) of DQ-113, gatifloxacin, and
      ciprofloxacin were 6.0, 41.3, and 131.6 mg/kg, respectively. Against PRSP-caused
      pneumonia in mice, the ED50s of DQ-113, gatifloxacin, and ciprofloxacin were 7.6,
      64.7, and 125.9 mg/kg, respectively. Compared with the other drugs, DQ-113 showed
      excellent therapeutic efficacy and eradicated viable bacteria in both PSSP- and
      PRSP-infected mice. The means +/- standard errors of the means of viable
      bacterium counts in the lungs of gatifloxacin-treated, ciprofloxacin-treated, and
      untreated control mice infected with PSSP were 2.91 +/- 0.34, 3.13 +/- 0.48, and
      3.86 +/- 0.80 log10 CFU/ml, respectively. The same counts in mice infected with
      PRSP treated with the same three agents were 6.57 +/- 0.99, 6.54 +/- 0.40, and
      7.17 +/- 0.43 log10 CFU/ml, respectively. DQ-113 significantly decreased the
      number of viable bacteria in the lungs compared with gatifloxacin and
      ciprofloxacin. Of the drugs analyzed, the pharmacokinetic-pharmacodynamic
      parameter of area under the concentration-time curve (AUC)/MIC ratio for DQ-113
      was significantly higher than those for gatifloxacin and ciprofloxacin. Our
      results suggest that DQ-113 has potent in vivo efficacy against both PSSP and
      PRSP.

PMID- 14638469
TI  - Effect of moxifloxacin on production of proinflammatory cytokines from human
      peripheral blood mononuclear cells.
AB  - The effects of moxifloxacin, a new methoxyfluoroquinolone, on the production of
      proinflammatory cytokines from human peripheral blood mononuclear cells (PBMCs)
      were evaluated. Moxifloxacin inhibited the production of tumor necrosis factor
      alpha (TNF-alpha) and/or interleukin-6 (IL-6) by PBMCs stimulated with
      lipopolysaccharide (LPS), lipoteichoic acid (LTA), and heat-killed bacteria in a
      concentration-dependent manner without cytotoxic effects. The addition of
      moxifloxacin reduced the population of cells positive for CD-14 and TNF-alpha and
      for CD-14 and IL-6 among the LPS- or LTA-stimulated PBMCs. By Western blot
      analysis, moxifloxacin pretreatment reduced the degradation of IkappaBalpha in
      LPS-stimulated PBMCs. In conclusion, moxifloxacin could interfere with NF-kappaB
      activation by inhibiting the degradation of IkappaBalpha and reduce the levels of
      production of proinflammatory cytokines.

PMID- 14638470
TI  - Antimalarial 9-anilinoacridine compounds directed at hematin.
AB  - Antimalarial 9-anilinoacridines are potent inhibitors of parasite DNA
      topoisomerase II both in vitro and in situ. 3,6-diamino substitution on the
      acridine ring greatly improves parasiticidal activity against Plasmodium
      falciparum by targeting DNA topoisomerase II. A series of 9-anilinoacridines were
      investigated for their abilities to inhibit beta-hematin formation, to form drug
      hematin complexes, and to enhance hematin-induced lysis of red blood cells.
      Inhibition of beta-hematin formation was minimal with 3,6-diamino analogs of 9
      anilinoacridine and greatest with analogs with a 3,6-diCl substitution together
      with an electron-donating group in the 1'-anilino position. On the other hand,
      the presence of a 1'-N(CH3)2 group in the anilino ring produced compounds that
      strongly inhibited beta-hematin formation but which did not appear to be
      sensitive to the nature of the substitutions in the acridine nucleus. The
      derivatives bound hematin, and Job's plots of UV-visible absorbance changes in
      drug-hematin complexes at various molar ratios indicated a stoichiometric ratio
      of 1:2. The drugs enhanced hematin-induced red blood cell lysis at low
      concentrations (<4 microM). These studies open up the novel possibility of
      development of 9-anilinoacridine antimalarials that target not only DNA
      topoisomerase II but also beta-hematin formation, which should help delay the
      rapid onset of resistance to drugs acting at only a single site.

PMID- 14638471
TI  - In vitro evaluation of a new treatment for urinary tract infections caused by
      nitrate-reducing bacteria.
AB  - Dietary and endogenous nitrates are excreted in urine, and during infection with
      nitrate-reducing bacteria they are reduced to nitrite. At a low pH nitrite is
      converted to a variety of nitrogen oxides that are toxic to bacteria. We
      hypothesized that acidification of nitrite-rich infected urine would result in
      the killing of the nitrate-reducing bacteria. An Escherichia coli control strain
      and a mutant lacking nitrate reductase activity were preincubated in urine
      supplemented with sodium nitrate (0 to 10 mM) at pH 7.0. Then, the nitrite
      containing bacterial culture was transferred (and diluted 1/10) to slightly
      acidic urine (pH 5 and 5.5) containing ascorbic acid (10 mM) and growth was
      monitored. The control strain produced nitrite in amounts related to the amount
      of nitrate added. This strain was killed when the culture was transferred to
      acidic urine. In contrast, the mutant that did not produce nitrite retained full
      viability. When control bacteria were grown in acidic urine with nitrate and
      ascorbic acid present from the start of the experiment, no inhibition of growth
      was noted. The MICs and minimal bactericidal concentrations of sodium nitrite
      ascorbic acid in acidic urine were comparable to those of conventional
      antibiotics. Preincubation of nitrate-reducing E. coli in nitrate-rich urine
      leads to the accumulation of nitrite. Subsequent acidification of the urine
      results in generation of nitrogen oxides that are bactericidal. Killing, however,
      requires a sequential procedure in which the bacteria are first allowed to grow
      in a nitrate-rich neutral environment, later followed by acidification. We
      speculate that ingestion of nitrate followed some hours later by acidification of
      urine could be a new therapeutic strategy for the treatment of urinary tract
      infections.

PMID- 14638472
TI  - Epidemiology of nalidixic acid resistance and TEM-1- and TEM-52-mediated
      ampicillin resistance of Shigella sonnei isolates obtained in Korea between 1980
      and 2000.
AB  - The resistance to ampicillin and nalidixic acid in Shigella sonnei isolates
      obtained in Korea during the period 1998 to 2000 was characterized. Recently (J.
      Y. Oh, H. S. Yu, S. K. Kim, S. Y. Seol, D. T. Cho, and J. C. Lee, J. Clin.
      Microbiol. 41:421-423, 2003) ampicillin and nalidixic acid resistance was found
      in 49 and 70%, respectively, of the 67 S. sonnei isolates obtained during this
      period. We analyzed 138 S. sonnei isolates collected during the same period.
      Ampicillin and nalidixic acid resistance was found in 30 and 86% of the isolates,
      respectively. The ampicillin resistance was mediated by a TEM-1 beta-lactamase,
      and TEM-52 extended-spectrum beta-lactamase was identified in one sporadic S.
      sonnei isolate from 1999. bla(TEM-1) and bla(TEM-52) were located in conjugative
      R-plasmids. Tn3 was detected in 41% of the ampicillin-resistant isolates. The R
      plasmids from the transconjugants that transferred resistance to ampicillin
      exhibited different restriction fragment length polymorphism patterns, and a
      bla(TEM-1) probe was hybridized with the different fragments. The nalidixic acid
      resistance was exclusively associated with an amino acid substitution, Ser83-
      >Leu (TCG-->TTG), in gyrA. These findings indicate that the genetically related
      S. sonnei strains readily acquire resistance to ampicillin, streptomycin,
      trimethoprim, and sulfamethoxazole but not nalidixic acid through conjugative R
      plasmids from difference sources when confronted by antibiotic selective
      pressures.

PMID- 14638473
TI  - Prevalence and molecular epidemiology of CTX-M extended-spectrum beta-lactamase
      producing Escherichia coli and Klebsiella pneumoniae in Russian hospitals.
AB  - A total of 904 consecutive nosocomial isolates of Escherichia coli and Klebsiella
      pneumoniae collected from 28 Russian hospitals were screened for production of
      extended-spectrum beta-lactamases (ESBLs). The ESBL phenotype was detected in 78
      (15.8%) E. coli and 248 (60.8%) K. pneumoniae isolates. One hundred fifteen
      isolates carried the genes for CTX-M-type beta-lactamases, which, as shown by PCR
      restriction fragment length polymorphism analysis, were distributed into the two
      genetic groups of CTX-M-1 (93%)- and CTX-M-2 (7%)-related enzymes. Isolates
      producing the enzymes of the first group were found in 20 hospitals from
      geographically distant regions of the country and were characterized by
      considerable diversity of genetic types, as was demonstrated by enterobacterial
      repetitive consensus PCR typing. Within this group the CTX-M-3 and the CTX-M-15
      beta-lactamases were identified. In contrast, the enzymes of the CTX-M-2 group
      (namely, CTX-M-5) were detected only in eight clonally related E. coli isolates
      from a single hospital. Notably, the levels of resistance to ceftazidime were
      remarkably variable among the CTX-M producers. This study provides further
      evidence of the global dissemination of CTX-M type ESBLs and emphasizes the need
      for their epidemiological monitoring.

PMID- 14638474
TI  - EfrAB, an ABC multidrug efflux pump in Enterococcus faecalis.
AB  - A DNA fragment responsible for resistance to antimicrobial agents was cloned from
      the chromosomal DNA of Enterococcus faecalis ATCC 29212 by using drug
      hypersensitive mutant Escherichia coli KAM32 as a host cell. Cells of E. coli
      KAM32 harboring a recombinant plasmid (pAEF82) carrying the DNA fragment became
      resistant to many structurally unrelated antimicrobial agents, such as
      norfloxacin, ciprofloxacin, doxycycline, acriflavine, 4',6-diamidino-2
      phenylindole, tetraphenylphosphonium chloride, daunorubicin, and doxorubicin.
      Since the sequence of the whole genome of E. faecalis is known, we sequenced
      several portions of the DNA insert in plasmid pAEF82 and identified two open
      reading frames within the insert. We designated the genes efrA and efrB. A search
      of the deduced amino acid sequences of EfrA and EfrB revealed that they are
      similar to each other and that they belong to the ATP-binding cassette (ABC)
      family of multidrug efflux transporters. Transformed E. coli KAM32 cells
      harboring efrAB showed energy-dependent efflux of acriflavine. The efflux
      activity was inhibited by reserpine, verapamil, and sodium-o-vanadate, known
      inhibitors of ABC efflux pumps.

PMID- 14638475
TI  - In vivo selection of a chromosomally encoded beta-lactamase variant conferring
      ceftazidime resistance in Klebsiella oxytoca.
AB  - Klebsiella oxytoca clinical isolate A was recovered from the urine of a 55-year
      old man with prostatic and urinary tract infections. This isolate displayed a
      beta-lactam resistance phenotype consistent with overproduction of a
      chromosomally encoded class A beta-lactamase and had decreased susceptibilities
      to all beta-lactams except ceftazidime, cephamycins, and carbapenems. Four weeks
      after treatment with an antibiotic regimen that included ceftazidime, K. oxytoca
      isolate B, which had a high level of resistance to ceftazidime, was isolated from
      the urine of the same patient. Isoelectric focusing analysis of the culture
      extracts of these isolates gave a pI of 5.4 for both isolates. Cloning
      experiments with the PCR products of the bla(OXY) gene resulted in two
      Escherichia coli DH10B recombinant clones with resistance phenotypes mirroring
      those of the parental isolates. Sequencing analysis revealed that the bla(OXY-2
      5) gene from K. oxytoca B had a single nucleotide substitution compared to the
      sequence of the bla(OXY-2) gene from K. oxytoca A, leading to a proline-to-serine
      substitution at position 167, according to the numbering of Ambler. Biochemical
      analysis of purified OXY-2-5 showed that it had the ability to hydrolyze
      ceftazidime. This is the first report of in vivo selection of a K. oxytoca
      isolate that produced a chromosomally encoded beta-lactamase conferring
      resistance to ceftazidime.

PMID- 14638476
TI  - Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with
      low fitness in vivo are defective in RpoS induction.
AB  - Mutants of Salmonella enterica serovar Typhimurium resistant to fusidic acid
      (Fusr) have mutations in fusA, the gene encoding translation elongation factor G
      (EF-G). Most Fusr mutants have reduced fitness in vitro and in vivo, in part
      explained by mutant EF-G slowing the rate of protein synthesis and growth.
      However, some Fusr mutants with normal rates of protein synthesis still suffer
      from reduced fitness in vivo. As shown here, Fusr mutants could be similarly
      ranked in their relative fitness in mouse infection models, in a macrophage
      infection model, in their relative hypersensitivity to hydrogen peroxide in vivo
      and in vitro, and in the amount of RpoS production induced upon entry into the
      stationary phase. We identify a reduced ability to induce production of RpoS
      (sigmas) as a defect associated with Fusr strains. Because RpoS is a regulator of
      the general stress response, and an important virulence factor in Salmonella, an
      inability to produce RpoS in appropriate amounts can explain the low fitness of
      Fusr strains in vivo. The unfit Fusr mutants also produce reduced levels of the
      regulatory molecule ppGpp in response to starvation. Because ppGpp is a positive
      regulator of RpoS production, we suggest that a possible cause of the reduced
      levels of RpoS is the reduction in ppGpp production associated with mutant EF-G.
      The low fitness of Fusr mutants in vivo suggests that drugs that can alter the
      levels of global regulators of gene expression deserve attention as potential
      antimicrobial agents.

PMID- 14638477
TI  - In vitro and in vivo antibacterial activities of DK-507k, a novel
      fluoroquinolone.
AB  - The antibacterial activities of DK-507k, a novel quinolone, were compared with
      those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin,
      moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as
      sitafloxacin and was as active as or up to eightfold more active than
      gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae,
      methicillin-susceptible and methicillin-resistant Staphylococcus aureus, and
      coagulase-negative staphylococci. DK-507k was as active as or 4-fold more active
      than garenoxacin and 2- to 16-fold more active than gatifloxacin and moxifloxacin
      against ciprofloxacin-resistant strains of S. pneumoniae, including clinical
      isolates and in vitro-selected mutants with known mutations. DK-507k inhibited
      all ciprofloxacin-resistant strains of S. pneumoniae at 1 microg/ml. A time-kill
      assay with S. pneumoniae showed that DK-507k was more bactericidal than
      gatifloxacin and moxifloxacin. The activities of DK-507k against most members of
      the family Enterobacteriaceae were comparable to those of ciprofloxacin and equal
      to or up to 32-fold higher than those of gatifloxacin, levofloxacin,
      moxifloxacin, and garenoxacin. DK-507k was fourfold less active than sitafloxacin
      and ciprofloxacin against Pseudomonas aeruginosa, while it was two to four times
      more potent than levofloxacin, gatifloxacin, moxifloxacin, and garenoxacin
      against P. aeruginosa. In vivo, intravenous treatment with DK-507k was more
      effective than that with gatifloxacin and moxifloxacin against systemic
      infections caused by S. aureus, S. pneumoniae, and P. aeruginosa in mice. In a
      mouse model of pneumonia due to penicillin-resistant S. pneumoniae, DK-507k
      administered subcutaneously showed dose-dependent efficacy and eliminated the
      bacteria from the lungs, whereas gatifloxacin and moxifloxacin had no significant
      efficacy. Oral treatment with DK-507k was slightly more effective than that with
      ciprofloxacin in a rat model of foreign body-associated urinary tract infection
      caused by a P. aeruginosa isolate for which the MIC of DK-507k was fourfold
      higher than that of ciprofloxacin. Oral administration of DK-507k to rats
      achieved higher peak concentrations in serum and higher concentrations in
      cumulative urine than those achieved with ciprofloxacin. These data indicate the
      potential advantages of DK-507k over other quinolones for the treatment of a wide
      range of community-acquired infections.

PMID- 14638478
TI  - In vitro activity of daptomycin against vancomycin-resistant enterococci of
      various Van types and comparison of susceptibility testing methods.
AB  - The increasing prevalence of vancomycin-resistant enterococcal (VRE) infections
      and the limited number of antimicrobial agents for their treatment emphasize a
      need for new, more effective agents. In this study, the in vitro activity of
      daptomycin was determined against a collection of 156 VRE from seven different
      institutions. Van types were characterized by PCR, and pulsed-field gel
      electrophoresis was performed to exclude isolates with >85% relatedness by
      dendrogram. Included were 126 Enterococcus faecium (109 vanA, 17 vanB) isolates,
      5 Enterococcus faecalis (3 vanA, 2 vanB) isolates, 2 Enterococcus avium (vanA)
      isolates, 1 Enterococcus durans (vanA) isolate, 10 Enterococcus gallinarum
      (vanC1) isolates, and 12 Enterococcus casseliflavus (vanC2) isolates. MICs of
      daptomycin and five additional agents were determined by the NCCLS broth
      microdilution method with Mueller-Hinton (MH) broth containing supplemental
      calcium. MICs were also determined using two investigational E-test strip
      formulations, and disk diffusion testing was performed by the standard NCCLS
      method. The MIC of daptomycin at which 50% of the isolates tested were inhibited
      for this isolate collection was 4 microg/ml, and the MIC at which 90% of the
      isolates tested were inhibited was 8 microg/ml. Two isolates of vanA E. faecium
      were resistant to linezolid, and one isolate was resistant to quinupristin
      dalfopristin. MICs of daptomycin determined by the E test with and without added
      calcium varied by 8- to 16-fold, and disk diffusion zones varied by 3 to 6 mm
      according to the calcium content of the commercial MH agar lots used in the
      study. This study has shown daptomycin to have good activity against a diverse
      collection of contemporary VRE isolates. However, improved standardization of the
      calcium content of MH agar will be important for reliable testing of daptomycin
      by clinical laboratories using either the E test or disk diffusion methods.

PMID- 14638479
TI  - Increased killing of staphylococci and streptococci by daptomycin compared with
      cefazolin and vancomycin in an in vitro peritoneal dialysate model.
AB  - Peritoneal dialysate fluid (PDF) is a bacteriostatic medium that compromises the
      antibacterial activity of cell wall-active agents. By use of an in vitro static
      model, methicillin-resistant Staphylococcus aureus (MRSA), methicillin
      susceptible S. aureus (MSSA), methicillin-susceptible Staphylococcus epidermidis
      (MSSE), and Streptococcus sanguis were exposed to daptomycin at concentrations of
      10, 30, and 100 mg/liter, cefazolin at 125 mg/liter, and vancomycin at 25
      mg/liter in cation-adjusted Mueller-Hinton Broth or Todd Hewitt Broth (for S.
      sanguis) and PDF at pHs of 5.5 and 7.4. The pH had no effect on antibacterial
      activity. Neither cefazolin nor vancomycin produced a bactericidal or a
      bacteriostatic effect versus MRSA, MSSA, MSSE, or S. sanguis in PDF, while all
      concentrations of daptomycin were bactericidal against all organisms in PDF.
      Daptomycin did not exhibit concentration-dependent activity in PDF. Daptomycin
      appears to be a promising agent for use in peritoneal dialysis-associated
      peritonitis, producing bacterial kill to a greater extent and at a higher rate
      than cefazolin or vancomycin in PDF.

PMID- 14638480
TI  - Efficacies of vancomycin, arbekacin, and gentamicin alone or in combination
      against methicillin-resistant Staphylococcus aureus in an in vitro infective
      endocarditis model.
AB  - We adopted an in vitro infective endocarditis model (IVIEM) to compare the
      efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in
      combination. Using two strains of clinically isolated methicillin-resistant
      Staphylococcus aureus, one GEN susceptible (GS171) and one GEN resistant (GR153),
      fibrin clots were prepared and suspended in the IVIEM. Antibiotics were given as
      boluses every 6 h (q6h), q12h, or q24h or by continuous infusion with VAN, q12h
      or q24h with ABK, and q8h or q24h with GEN. For combination treatment, VAN q12h
      plus ABK q24h and VAN q12h plus GEN q24h were given. Fibrin clots were removed
      from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities were
      determined. The number of colonies within the fibrin clot was significantly
      decreased in all study groups compared with control groups (P<0.001). When VAN
      and ABK were administered alone, the number of colonies was significantly lower
      in GS171 than in GR153 by 8 h after administration (P=0.02) and was lowest in
      GS171 when ABK was administered q12h (P=0.01). At 72 h, ABK or VAN alone produced
      equivalent bacterial reductions regardless of dosing frequency and GEN
      resistance. In GR153, VAN plus ABK showed an additive effect till 24 h, although
      VAN plus GEN showed indifference. Our data suggest that ABK could be used as an
      alternative to VAN in GEN-resistant staphylococcal endocarditis. An additive
      effect was seen when VAN and ABK were used together in GEN-resistant strains
      until 24 h; however, further studies are warranted for the clinical application
      of this combination.

PMID- 14638481
TI  - Toxicity and antileishmanial activity of a new stable lipid suspension of
      amphotericin B.
AB  - The aim of the present study was to evaluate the toxicity and the activity of a
      new lipid complex formulation of amphotericin B (AMB) (LC-AMB; dimyristoyl
      phosphatidylcholine, dimyristoyl phosphatidylglycerol, and AMB) that can be
      produced by a simple process. Like other lipid formulations, this new complex
      reduced both the hemolytic activity of AMB (the concentration causing 50%
      hemolysis of human erythrocytes, >100 microg/ml) and its toxicity toward murine
      peritoneal macrophages (50% inhibitory concentration, >100 microg/ml at 24 h).
      The in vivo toxicity of the new formulation (50% lethal dose, >200 mg/kg of body
      weight for CD1 mice) was similar to those of other commercial lipid formulations
      of AMB. The complex was the most effective formulation against the DD8 strain of
      Leishmania donovani. It was unable to reverse the resistance of an AMB-resistant
      L. donovani strain. In vivo LC-AMB was less efficient than AmBisome against L.
      donovani.

PMID- 14638482
TI  - Nitazoxanide in treatment of Helicobacter pylori: a clinical and in vitro study.
AB  - Nitazoxanide (NTZ) is an antibiotic with microbiological characteristics similar
      to those of metronidazole but without an apparent problem of resistance. The aim
      of this study was the prospective evaluation of NTZ given as a single agent in
      the treatment of Helicobacter pylori infection. Twenty culture-positive patients
      with dyspepsia who had previously failed at least one course of H. pylori
      eradication therapy were enrolled. Subjects received 1 g of NTZ twice daily for
      10 days. The safety and tolerability of the drug were assessed by physical
      examination, monitoring of adverse events, and clinical laboratory evaluation.
      Urea breath tests (UBTs) were performed 6 weeks posttreatment. H. pylori was
      isolated from UBT-positive patients by the string test or endoscopy with biopsy,
      and the MICs for these isolates were compared to those for isolates obtained
      pretherapy. The levels of tizoxanide, the active deacylated derivative of NTZ,
      were measured in blood, saliva, and tissue from two patients during treatment.
      The UBT results were positive for all 20 patients after completion of NTZ
      therapy. The MIC results demonstrated that the NTZ susceptibilities of none of
      the strains isolated from the patients posttherapy had changed significantly. No
      major adverse reactions were observed, but frequent minor side effects were
      observed. In conclusion, NTZ did not eradicate H. pylori when it was given as a
      single agent.

PMID- 14638483
TI  - Evaluations of unformulated and formulated dendrimer-based microbicide candidates
      in mouse and guinea pig models of genital herpes.
AB  - Prevention of sexually transmitted infections is a priority in developed and
      developing countries. One approach to prevention is the use of topical
      microbicides, and one promising approach is the use of dendrimers, highly
      branched macromolecules synthesized from a polyfunctional core. Three new
      dendrimer products developed to provide stable and cost-efficient microbicides
      were initially evaluated in vitro for anti-herpes simplex virus activity and then
      in vivo by using a mouse model of genital herpes. From these experiments one
      product, SPL7013, was chosen for further evaluation to define the dose and
      duration of protection. Unformulated SPL7013 provided significant protection from
      genital herpes disease and infection at concentrations as low as 1 mg/ml and for
      at least 1 h following topical (intravaginal) administration of 10 mg/ml. This
      compound was then formulated into three vehicles and further evaluated in mouse
      and guinea pig models of genital herpes infection. In the murine evaluations each
      of the formulations provided significant protection at concentrations of 10 and
      50 mg/ml. Formulated compounds provided protection for at least 1 h at a
      concentration of 10 mg/ml. From these experiments formulation 2V was chosen for
      dose ranging experiments using the guinea pig model of genital herpes. The guinea
      pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal
      protection. From these studies a lead compound and formulation (2V of SPL7013)
      was chosen for ongoing evaluations in primate models of simian immunodeficiency
      virus and Chlamydia trachomatis infection.

PMID- 14638484
TI  - Concentrations in plasma, urinary excretion, and bactericidal activity of
      linezolid (600 milligrams) versus those of ciprofloxacin (500 milligrams) in
      healthy volunteers receiving a single oral dose.
AB  - In a randomized crossover study, 12 volunteers (6 males, 6 females) received a
      single oral dose of 600 mg of linezolid or 500 mg of ciprofloxacin to assess the
      concentrations in plasma (up to 24 h), urinary excretion (by high-pressure liquid
      chromatography), and bactericidal titers in urine (UBT) at intervals up to 120 h.
      The mean maximum concentration of linezolid in plasma was 13.1 mg/liter, and that
      of ciprofloxacin was 2.46 mg/liter. The median cumulative levels of renal
      excretion of the administered dose of the parent drug were 44% for linezolid
      (range, 28 to 47%; mean +/- standard deviation, 40% +/- 7.8%) and 43% for
      ciprofloxacin (range, 20 to 56%; mean +/- standard deviation, 40% +/- 9.3%). The
      UBTs, i.e., the highest twofold dilution (with antibiotic-free urine used as the
      diluent) of urine that was still bactericidal, were determined for a reference
      strain and five gram-positive clinical uropathogens for which the MICs of
      linezolid and ciprofloxacin were as follows: Staphylococcus aureus ATCC 27278, 2
      and 0.25 mg/liter, respectively; Staphylococcus aureus (methicillin susceptible),
      1 and 16 mg/liter, respectively; Staphylococcus aureus (methicillin resistant), 2
      and 64 mg/liter, respectively; Staphylococcus saprophyticus (methicillin
      susceptible), 1 and 0.25 mg/liter, respectively; Enterococcus faecalis, 2 and 1
      mg/liter, respectively; and Enterococcus faecium, 2 and 1 mg/liter, respectively.
      The median UBTs of linezolid measured within the first 6 h were 1:96 for each of
      the two enterococcal strains and between 1:128 and 1:256 for the four
      staphylococcal strains. The median UBTs of ciprofloxacin were 1:64 for the two
      enterococcal strains; between 1:384 and 1:512 for the two ciprofloxacin
      susceptible strains; and 1 (bactericidal activity of undiluted urine only) and
      1:2 for the two resistant staphylococcal strains, respectively. The areas under
      the UBT-time curve (AUBT) for linezolid and ciprofloxacin showed no statistically
      significant (P<0.05) differences except for a better AUBT for linezolid for the
      two ciprofloxacin-resistant staphylococcal strains. For linezolid there were no
      statistically significant differences in UBTs or AUBTs for ciprofloxacin
      susceptible and -resistant strains. Thus, the bactericidal activities of
      linezolid and ciprofloxacin against susceptible strains in urine were comparable,
      whereas linezolid also exhibited the same good bactericidal activity against
      ciprofloxacin-resistant strains. Therefore, linezolid should be tested for use as
      empirical treatment for complicated urinary tract infections due to gram-positive
      uropathogens in an appropriate clinical trial.

PMID- 14638485
TI  - Artemether bioavailability after oral or intramuscular administration in
      uncomplicated falciparum malaria.
AB  - The antimalarial activity of artemether following oral or intramuscular
      administration in the plasma of 15 adults with acute uncomplicated Plasmodium
      falciparum malaria was measured by bioassay. The peak concentrations in plasma
      following oral administration were higher in patients with acute illness (median,
      1,905 mmol of dihydroartemisinin [DHA] equivalents per liter; range, 955 to 3,358
      mmol of DHA equivalents per liter) than in patients in the convalescent phase
      (median, 955 mmol of DHA equivalents per liter; range, 576 to 1,363 mmol of DHA
      equivalents per liter), and clearance (CL/F) was lower in patients in the acute
      phase (1.11 liters/kg/h; range, 0.21 to 3.08 liters/kg/h) than in patients in the
      convalescent phase (median, 2.76 liters/kg/h; range, 1.56 to 5.74 liters/kg/h)
      (P< or =0.008). Antimalarial activity in terms of the peak concentration in
      plasma (Cmax) after oral administration was a median of 16 times higher than that
      after intramuscular administration. The ratio of the area under the plasma
      concentration-time curve during the first 24 h (AUC(0-24)) after oral
      administration of artemether to the AUC(0-24) after intramuscular administration
      was a median of 3.3 (range, 1 to 11) (P=0.0001). In the acute phase, the time to
      Cmax was significantly shorter after oral administration (median, 1 h; range, 0.5
      to 3.0 h) than after intramuscular administration (median, 8 h; range, 4 to 24 h)
      (P=0.001). Intramuscular artemether is absorbed very slowly in patients with
      acute malaria.

PMID- 14638486
TI  - ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium
      tuberculosis isolates.
AB  - Ethionamide (ETH) is a structural analog of the antituberculosis drug isoniazid
      (INH). Both of these drugs target InhA, an enzyme involved in mycolic acid
      biosynthesis. INH requires catalase-peroxidase (KatG) activation, and mutations
      in katG are a major INH resistance mechanism. Recently an enzyme (EthA) capable
      of activating ETH has been identified. We sequenced the entire ethA structural
      gene of 41 ETH-resistant Mycobacterium tuberculosis isolates. We also sequenced
      two regions of inhA and all or part of katG. The MICs of ETH and INH were
      determined in order to associate the mutations identified with a resistance
      phenotype. Fifteen isolates were found to possess ethA mutations, for all of
      which the ETH MICs were > or =50 microg/ml. The ethA mutations were all
      different, previously unreported, and distributed throughout the gene. In eight
      of the isolates, a missense mutation in the inhA structural gene occurred. The
      ETH MICs for seven of the InhA mutants were > or =100 microg/ml, and these
      isolates were also resistant to > or =8 microg of INH per ml. Only a single point
      mutation in the inhA promoter was identified in 14 isolates. A katG mutation
      occurred in 15 isolates, for which the INH MICs for all but 1 were > or =32
      microg/ml. As expected, we found no association between katG mutation and the
      level of ETH resistance. Mutations within the ethA and inhA structural genes were
      associated with relatively high levels of ETH resistance. Approximately 76% of
      isolates resistant to > or =50 microg of ETH per ml had such mutations.

PMID- 14638487
TI  - 5HT1A serotonin receptor agonists inhibit Plasmodium falciparum by blocking a
      membrane channel.
AB  - To identify new leads for the treatment of Plasmodium falciparum malaria, we
      screened a panel of serotonin (5-hydroxytryptamine [5HT]) receptor agonists and
      antagonists and determined their effects on parasite growth. The 5HT1A receptor
      agonists 8-hydroxy-N-(di-n-propyl)-aminotetralin (8-OH-DPAT), 2,5-dimethoxy-4
      iodoamphetamine, and 2,5-dimethoxy-4-bromophenylethylamine inhibited the growth
      of P. falciparum in vitro (50% inhibitory concentrations, 0.4, 0.7, and 1.5
      microM, respectively). In further characterizing the antiparasitic effects of 8
      OH-DPAT, we found that this serotonin receptor agonist did not affect the growth
      of Leishmania infantum, Trypanosoma cruzi, Trypanosoma brucei brucei, or
      Trichostrongylus colubriformis in vitro and did not demonstrate cytotoxicity
      against the human lung fibroblast cell line MRC-5. 8-OH-DPAT had similar levels
      of growth inhibition against several different P. falciparum isolates having
      distinct chemotherapeutic resistance phenotypes, and its antimalarial effect was
      additive when it was used in combination with chloroquine against a chloroquine
      resistant isolate. In a patch clamp assay, 8-OH-DPAT blocked a P. falciparum
      surface membrane channel, suggesting that serotonin receptor agonists are a novel
      class of antimalarials that target a nutrient transport pathway. Since there may
      be neurological involvement with the use of 8-OH-DPAT and other serotonin
      receptor agonists in the treatment of falciparum malaria, new lead compounds
      derived from 8-OH-DPAT will need to be modified to prevent potential neurological
      side effects. Nevertheless, these results suggest that 8-OH-DPAT is a new lead
      compound with which to derive novel antimalarial agents and is a useful tool with
      which to characterize P. falciparum membrane channels.

PMID- 14638488
TI  - Antimalarial activities of novel synthetic cysteine protease inhibitors.
AB  - Among promising new targets for antimalarial chemotherapy are the cysteine
      protease hemoglobinases falcipain-2 and falcipain-3. We evaluated the activities
      of synthetic peptidyl aldehyde and alpha-ketoamide cysteine protease inhibitors
      against these proteases, against cultured Plasmodium falciparum parasites, and in
      a murine malaria model. Optimized compounds inhibited falcipain-2 and falcipain
      3, blocked hemoglobin hydrolysis, and prevented the development of P. falciparum
      at nanomolar concentrations. The compounds were equally active against multiple
      strains of P. falciparum with varied sensitivities to standard antimalarial
      agents. The peptidyl inhibitors were consistently less active against vinckepain
      2, the putative falcipain-2 and falcipain-3 ortholog of the rodent malaria
      parasite Plasmodium vinckei. The lead compound morpholinocarbonyl-leucine
      homophenylalanine aldehyde, which blocked P. falciparum development at low
      nanomolar concentrations, was tested in a murine P. vinckei model. When infused
      continuously at a rate of 30 mg/kg of body weight/day, the compound delayed the
      progression of malaria but did not eradicate infections. Our data demonstrate the
      potent antimalarial activities of novel cysteine protease inhibitors.
      Additionally, they highlight the importance of consideration of the specific
      enzyme targets of animal model parasites. In the case of falcipains, differences
      between P. falciparum and rodent parasites complicate the use of the rodent
      malaria model in the drug discovery process.

PMID- 14638489
TI  - Antipneumococcal activity of DK-507k, a new quinolone, compared with the
      activities of 10 other agents.
AB  - Agar dilution MIC determination was used to compare the activity of DK-507k with
      those of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, sitafloxacin,
      amoxicillin, cefuroxime, erythromycin, azithromycin, and clarithromycin against
      113 penicillin-susceptible, 81 penicillin-intermediate, and 67 penicillin
      resistant pneumococci (all quinolone susceptible). DK-507k and sitafloxacin had
      the lowest MICs of all quinolones against quinolone-susceptible strains (MIC at
      which 50% of isolates were inhibited [MIC50] and MIC90 of both, 0.06 and 0.125
      microg/ml, respectively), followed by moxifloxacin, gatifloxacin, levofloxacin,
      and ciprofloxacin. MICs of beta-lactams and macrolides rose with those of
      penicillin G. Against 26 quinolone-resistant pneumococci with known resistance
      mechanisms, DK-507k and sitafloxacin were also the most active quinolones (MICs,
      0.125 to 1.0 microg/ml), followed by moxifloxacin, gatifloxacin, levofloxacin,
      and ciprofloxacin. Mutations in quinolone resistance-determining regions of
      quinolone-resistant strains were in the usual regions of the parC and gyrA genes.
      Time-kill testing showed that both DK-507k and sitafloxacin were bactericidal
      against all 12 quinolone-susceptible and -resistant strains tested at twice the
      MIC at 24 h. Serial broth passages in subinhibitory concentrations of 10 strains
      for a minimum of 14 days showed that development of resistant mutants (fourfold
      or greater increase in the original MIC) occurred most rapidly for ciprofloxacin,
      followed by moxifloxacin, DK-507k, gatifloxacin, sitafloxacin, and levofloxacin.
      All parent strains demonstrated a fourfold or greater increase in initial MIC in
      <50 days. MICs of DK-507k against resistant mutants were lowest, followed by
      those of sitafloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and
      levofloxacin. Four strains were subcultured in subinhibitory concentrations of
      each drug for 50 days: MICs of DK-507k against resistant mutants were lowest,
      followed by those of sitafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and
      ciprofloxacin. Exposure to DK-507k and sitafloxacin resulted in mutations, mostly
      in gyrA.

PMID- 14638490
TI  - Antimicrobial resistance in Campylobacter jejuni and Campylobacter coli strains
      isolated in 1991 and 2001-2002 from poultry and humans in Berlin, Germany.
AB  - The susceptibilities of 430 Campylobacter jejuni strains and 79 C. coli strains
      to six antimicrobial agents were tested and analyzed. The two sets of strains
      originated from retail market chicken and turkey samples and from humans,
      respectively, in Berlin, Germany. Two groups of isolates, one dating from 1991
      and the other dating from 2001-2002, were tested. Of the Campylobacter sp.
      isolates recovered from humans in 2001-2002, 45.1% were resistant to
      ciprofloxacin, 37.8% were resistant to tetracycline, 12.8% were resistant to
      ampicillin, and 50.0% were resistant to trimethoprim-sulfamethoxazole. All
      isolates were susceptible to gentamicin, while the overall rate of resistance to
      erythromycin was 6.1%. During the 10 years between the two sampling times, the
      rates of resistance to ciprofloxacin (P<0.001), ampicillin (P=0.035), and
      tetracycline (P=0.01) increased significantly among strains isolated from humans.
      Furthermore, among human C. coli strains the rate of resistance to erythromycin
      rose from 7.1% in 1991 to 29.4% in 2001-2002. In comparison, Campylobacter sp.
      isolates from poultry already had high rates of resistance in 1991. Different
      rates of resistance to tetracycline among isolates from chickens and turkeys
      suggested the development of resistance during antimicrobial treatment in food
      animals. Thus, discrepancies in the antimicrobial resistance rates among
      Campylobacter isolates originating from poultry and humans support the hypothesis
      that at least some of the resistant Campylobacter strains causing infection in
      humans come from sources other than poultry products.

PMID- 14638491
TI  - Novel antibacterial class.
AB  - We report the discovery and characterization of a novel ribosome inhibitor (NRI)
      class that exhibits selective and broad-spectrum antibacterial activity.
      Compounds in this class inhibit growth of many gram-positive and gram-negative
      bacteria, including the common respiratory pathogens Streptococcus pneumoniae,
      Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis, and are
      nontoxic to human cell lines. The first NRI was discovered in a high-throughput
      screen designed to identify inhibitors of cell-free translation in extracts from
      S. pneumoniae. The chemical structure of the NRI class is related to
      antibacterial quinolones, but, interestingly, the differences in structure are
      sufficient to completely alter the biochemical and intracellular mechanisms of
      action. Expression array studies and analysis of NRI-resistant mutants confirm
      this difference in intracellular mechanism and provide evidence that the NRIs
      inhibit bacterial protein synthesis by inhibiting ribosomes. Furthermore,
      compounds in the NRI series appear to inhibit bacterial ribosomes by a new
      mechanism, because NRI-resistant strains are not cross-resistant to other
      ribosome inhibitors, such as macrolides, chloramphenicol, tetracycline,
      aminoglycosides, or oxazolidinones. The NRIs are a promising new antibacterial
      class with activity against all major drug-resistant respiratory pathogens.

PMID- 14638492
TI  - GeneHunter, a transposon tool for identification and isolation of cryptic
      antibiotic resistance genes.
AB  - GeneHunter is a transposon tool designed for the experimental activation and
      identification of silent antibiotic resistance genes. The method permits the
      identification of novel resistance genes that lack previously identified
      homologues. Using Salmonella enterica serovar Typhimurium strain LT2 as a test
      organism for the in vivo version of the GeneHunter method, we were able to
      activate, clone, and identify two cryptic antibiotic resistance genes, the
      aminoglycoside acetyltransferase aac(6')-Iaa and the probable Mar-A regulon
      activator rma. Because the method requires being able to electroporate the host
      with an efficiency of at least 10(10) transformants per microgram, the in vivo
      method is not applicable to most microorganisms. We therefore developed an in
      vitro transposition method, showed that it can also recover the cryptic rma gene
      from S. enterica serovar Typhimurium strain LT2, and showed that it is generally
      applicable to a variety of microorganisms by using it to recover a cryptic
      metallo-beta-lactamase gene from the gram-positive organism Bacillus cereus. It
      is anticipated that the GeneHunter method will be used to identify potential
      resistance genes during the development and testing of novel antibiotics, new
      variants of existing antibiotics, and drug inhibitor combinations.

PMID- 14638493
TI  - Randomized, single-blind, placebo-controlled study of topical application of the
      immune response modulator resiquimod in healthy adults.
AB  - Resiquimod is a Toll-like receptor 7 (TLR7) and TLR8 agonist that is a potent
      inducer of alpha interferon (IFN-alpha) and other cytokines. The effects of
      multiple applications of resiquimod gel were assessed in a randomized, single
      blind, dose-ranging, placebo-controlled study with 41 healthy subjects. Over a 3
      week period, 1-g doses of resiquimod or vehicle gel (3:1 randomization) were
      applied to a 50-cm2 area of the upper arm according to the following regimens:
      0.25% applied for 8 h two times per week, 0.05% applied for 8 h two times per
      week, 0.05% applied for 8 h three times per week, and 0.01% applied for 24 h
      three times per week. Skin biopsy specimens were obtained prior to the
      application of the first dose and after the completion of application of the last
      dose. Dosing with 0.01 and 0.05% resiquimod was well tolerated, but that with
      0.25% was not; a dose-response relationship for local adverse effects was
      observed. The level of systemic exposure during multiple topical dosings was <1%
      of the applied dose. A significant increase in responders after completion of
      application of the last dose was observed for serum IFN and the interleukin-1 (IL
      1) receptor antagonist (P<0.01, Fisher's exact test). Increased levels of mRNA
      for IL-6, IL-8, IFN-alpha, and Mx (an IFN-alpha-inducible protein) were seen in
      posttreatment biopsy specimens from the group receiving 0.25% resiquimod compared
      to the levels seen in specimens from the group receiving vehicle only (P<0.01,
      Wilcoxon rank sum test). A dose-response-related increase in CD3-positive cells
      consistent with T-lymphocyte infiltration and a decrease in CD1a-positive cells,
      consistent with emigration of Langerhans' cells, were observed in treated skin.
      This study suggests that resiquimod is a potent topically active immune response
      modifier that significantly enhances the cutaneous immune response.

PMID- 14638494
TI  - Activity of 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine against
      Schistosomiasis mansoni in mice.
AB  - The activity of the acyclic nucleotide analogue 9-(S)-[3-hydroxy-2
      (phosphonomethoxy)propyl]adenine [(S)-HPMPA] against Schistosoma mansoni was
      investigated in mice. The compound was injected intraperitoneally, usually on two
      or five consecutive days, at 10 to 20 mg/kg of body weight/day. The treatment
      started before, at the time of, and after the onset of egg laying (oviposition)
      by S. mansoni. The animals were killed from 7 to 40 days after the cessation of
      treatment. Significant reductions in the total numbers of female and coupled
      worms were found. Female fecundity and both hepatic and intestinal egg loads were
      suppressed. These effects were more pronounced with dosing regimens launched
      before the time of oviposition. The complete disappearance of immature eggs and a
      significant reduction to the complete absence of mature eggs, with 99 to 100% of
      the eggs being dead, were produced. No hepatic egg-induced granulomas were
      present in mice treated at the time of oviposition, and the granulomas were
      smaller in mice treated before S. mansoni oviposition. These preliminary findings
      extend the knowledge of the antiparasitic properties of (S)-HPMPA.

PMID- 14638495
TI  - Triclosan as a systemic antibacterial agent in a mouse model of acute bacterial
      challenge.
AB  - The upsurge of multiple-drug-resistant microbes warrants the development and/or
      use of effective antibiotics. Triclosan, though used in cosmetic and
      dermatological preparations for several decades, has not been used as a systemic
      antibacterial agent due to problems of drug administration. Here we report the
      striking efficacy of triclosan in a mouse model of acute systemic bacterial
      infection. Triclosan not only significantly extends the survival time of the
      infected mice, it also restores blood parameters and checks liver damage induced
      by the bacterial infection. We believe that the excellent safety track record of
      triclosan in topical use coupled with our findings qualifies triclosan as a
      candidate drug or lead compound for exploring its potential in experimental
      systems for treating systemic bacterial infections.

PMID- 14638496
TI  - aph(3')-IIb, a gene encoding an aminoglycoside-modifying enzyme, is under the
      positive control of surrogate regulator HpaA.
AB  - Pseudomonas aeruginosa harbors a chromosomal aminoglycoside phosphotransferase
      gene, aph(3')-IIb, which confers P. aeruginosa resistance to several important
      aminoglycoside antibiotics, including kanamycin A and B, neomycin B and C,
      butirosin, and seldomycin F5. The aph(3')-IIb gene has been found to be regulated
      by an AraC-type transcriptional regulator (HpaA) encoded by a gene located
      upstream of the aph(3')-IIb gene. In the presence of 4-hydroxyphenylacetic acid
      (4-HPA), HpaA activates the expression of aph(3')-IIb as well as that of the hpa
      regulon which encodes metabolic enzymes for the utilization of 4-HPA. hpaA and
      aph(3')-IIb form an operon, and in response to the presence of 4-HPA, the wild
      type P. aeruginosa strain PAK (but not its hpaA mutant strain) displays increased
      resistance to neomycin. A survey of 39 clinical and 19 environmental isolates of
      P. aeruginosa demonstrated in all of them the presence of an hpaA-aph gene
      cluster, while 56 out of the 58 isolates are able to utilize the 4-HPA as a sole
      carbon source, suggesting a feature common to P. aeruginosa strains.
      Interestingly, a larger portion of clinical isolates than environmental isolates
      showed 4-HPA-induced resistance to neomycin. The aph(3')-IIb gene product is
      likely to function as a metabolic enzyme which has a cross-reactivity with
      aminoglycosides. These findings provide new insight into the possible mechanism
      of P. aeruginosa antibiotic resistance.

PMID- 14638497
TI  - Acquired macrolide resistance genes in pathogenic Neisseria spp. isolated between
      1940 and 1987.
AB  - Seventy-six Neisseria gonorrhoeae isolates, isolated between 1940 and 1987, and
      seven Neisseria meningitidis isolates, isolated between 1963 and 1987, were
      screened for the presence of acquired mef(A), erm(B), erm(C), and erm(F) genes by
      using DNA-DNA hybridization, PCR analysis, and sequencing. The mef(A), erm(B),
      and erm(F) genes were all identified in a 1955 N. gonorrhoeae isolate, while the
      erm(C) gene was identified in a 1963 N. gonorrhoeae isolate. Similarly, both the
      mef(A) and erm(F) genes were identified in a 1963 N. meningitidis isolate. All
      four acquired genes were found in later isolates of both species. The mef(A) gene
      from a 1975 N. gonorrhoeae isolate was sequenced and had 100% DNA and amino acid
      identity with the mef(A) gene from a 1990s Streptococcus pneumoniae isolate.
      Selected early isolates were able to transfer their acquired genes to an
      Enterococcus faecalis recipient, suggesting that these genes are associated with
      conjugative transposons. These isolates are the oldest of any species to carry
      the mef(A) gene and among the oldest to carry these erm genes.

PMID- 14638498
TI  - Carbapenem-resistant strain of Klebsiella oxytoca harboring carbapenem
      hydrolyzing beta-lactamase KPC-2.
AB  - We investigated a Klebsiella oxytoca isolate demonstrating resistance to
      imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The MICs of
      both imipenem and meropenem were 32 microg/ml. The beta-lactamase activity
      against imipenem and meropenem was inhibited in the presence of clavulanic acid.
      Isoelectric focusing studies demonstrated five beta-lactamases with pIs of 8.2
      (SHV-46), 6.7 (KPC-2), 6.5 (unknown), 6.4 (probable OXY-2), and 5.4 (TEM-1). The
      presence of the bla(SHV) and bla(TEM) genes was confirmed by specific PCR assays
      and DNA sequence analysis. Transformation and conjugation studies with
      Escherichia coli showed that the beta-lactamase with a pI of 6.7, Klebsiella
      pneumoniae carbapenemase-2 (KPC-2), was encoded on an approximately 70-kb
      conjugative plasmid that also carried SHV-46, TEM-1, and the beta-lactamase with
      a pI of 6.5. The bla(KPC-2) determinant was cloned in E. coli and conferred
      resistance to imipenem, meropenem, extended-spectrum cephalosporins, and
      aztreonam. The amino acid sequence of KPC-2 showed a single amino acid
      difference, S174G, when compared with KPC-1, another carbapenem-hydrolyzing beta
      lactamase from K. pneumoniae 1534. Hydrolysis studies showed that purified KPC-2
      hydrolyzed not only carbapenems but also penicillins, cephalosporins, and
      aztreonam. KPC-2 had the highest affinity for meropenem. The kinetic studies
      revealed that KPC-2 was inhibited by clavulanic acid and tazobactam. An
      examination of the outer membrane proteins of the parent K. oxytoca strain
      demonstrated that it expressed detectable levels of OmpK36 (the homolog of OmpC)
      and a higher-molecular-weight OmpK35 (the homolog of OmpF). Thus, carbapenem
      resistance in K. oxytoca 3127 is due to production of the Bush group 2f, class A,
      carbapenem-hydrolyzing beta-lactamase KPC-2. This beta-lactamase is likely
      located on a transposon that is part of a conjugative plasmid and thus has a very
      high potential for dissemination.

PMID- 14638500
TI  - Novispirin G10-induced lung toxicity in a Klebsiella pneumoniae infection model.
AB  - Mammalian cathelicidins are a class of innate antimicrobial peptides isolated
      from leukocytes and epithelial cells that aid host defense against bacterial
      infections. Synthetic analogs of cathelicidins offer the promise of potent broad
      spectrum antimicrobial efficacy. We developed a combined lung infection and ex
      vivo whole-blood assay model to characterize the toxicity and efficacy of
      synthetic cathelicidin-derived peptides. Male C57BL/6 mice were administered
      saline or Klebsiella pneumoniae by intratracheal instillation. Five hours later,
      the Klebsiella-infected mice were instilled with saline, tobramycin (1 mg/kg of
      body weight or 10 mg/kg), novispirin G10 (0.4 mg/kg), or a combination of
      tobramycin (1 mg/kg) and G10 (0.4 mg/kg). At 24 h, bronchoalveolar lavage fluid
      (BAL) was collected for analysis of culturable bacteria and for markers of
      inflammation and lung toxicity. Blood samples were analyzed for circulating
      cytokines. Recovery of Klebsiella from the lung, recruitment of neutrophils, and
      production of interleukin-6 (IL-6) in BAL samples were highly correlated (r=0.68
      and 0.84, respectively; P<0.01). Animals treated with G10 or G10 plus tobramycin
      had increased hemoglobin (P<0.001) and protein (P<0.001) levels compared to those
      for Klebsiella-infected or tobramycin-alone-treated animals. The levels of
      circulating IL-6 in mice infected with Klebsiella were 1000- to 10,000-fold
      higher than in the noninfected controls. The highest levels of IL-6 were measured
      in mice given G10 alone or in combination with tobramycin. These studies
      demonstrated that G10 was relatively nontoxic in saline-treated mice but was
      highly toxic in mice infected with Klebsiella. This finding establishes the
      importance of investigating candidate antimicrobial agents in an in vivo
      infection model.

PMID- 14638499
TI  - Molecular mechanism of terbinafine resistance in Saccharomyces cerevisiae.
AB  - Ten mutants of the yeast Saccharomyces cerevisiae resistant to the antimycotic
      terbinafine were isolated after chemical or UV mutagenesis. Molecular analysis of
      these mutants revealed single base pair exchanges in the ERG1 gene coding for
      squalene epoxidase, the target of terbinafine. The mutants did not show cross
      resistance to any of the substrates of various pleiotropic drug resistance efflux
      pumps tested. The ERG1 mRNA levels in the mutants did not differ from those in
      the wild-type parent strains. Terbinafine resistance was transmitted with the
      mutated alleles in gene replacement experiments, proving that single amino acid
      substitutions in the Erg1 protein were sufficient to confer the resistance
      phenotype. The amino acid changes caused by the point mutations were clustered in
      two regions of the Erg1 protein. Seven mutants carried the amino acid
      substitutions F402L (one mutant), F420L (one mutant), and P430S (five mutants) in
      the C-terminal part of the protein; and three mutants carried an L251F exchange
      in the central part of the protein. Interestingly, all exchanges identified
      involved amino acids which are conserved in the squalene epoxidases of yeasts and
      mammals. Two mutations that were generated by PCR mutagenesis of the ERG1 gene
      and that conferred terbinafine resistance mapped in the same regions of the Erg1
      protein, with one resulting in an L251F exchange and the other resulting in an
      F433S exchange. The results strongly indicate that these regions are responsible
      for the interaction of yeast squalene epoxidase with terbinafine.

PMID- 14638501
TI  - Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir
      nasal spray 2-percent suspension for prevention and treatment of experimentally
      induced rhinovirus colds in healthy volunteers.
AB  - Human rhinovirus (HRV) infections are usually self-limited but may be associated
      with serious consequences, particularly in those with asthma and chronic
      respiratory disease. Effective antiviral agents are needed for preventing and
      treating HRV illnesses. Ruprintrivir (Agouron Pharmaceuticals, Inc., San Diego,
      Calif.) selectively inhibits HRV 3C protease and shows potent, broad-spectrum
      anti-HRV activity in vitro. We conducted three double-blind, placebo-controlled
      clinical trials in 202 healthy volunteers to assess the activity of ruprintrivir
      in experimental HRV infection. Subjects were randomized to receive intranasal
      ruprintrivir (8 mg) or placebo sprays as prophylaxis (two or five times daily
      [2x/day or 5x/day] for 5 days) starting 6 h before infection or as treatment
      (5x/day for 4 days) starting 24 h after infection. Ruprintrivir prophylaxis
      reduced the proportion of subjects with positive viral cultures (for 5x/day
      dosing groups, 44% for ruprintrivir treatment group versus 70% for placebo
      treatment group [P=0.03]; for 2x/day dosing groups, 60% for ruprintrivir group
      versus 92% for placebo group [P=0.004]) and viral titers but did not decrease the
      frequency of colds. Ruprintrivir treatment reduced the mean total daily symptom
      score (2.2 for ruprintrivir treatment group and 3.3 for the placebo treatment
      group [P=0.014]) by 33%. Secondary endpoints, including viral titers, individual
      symptom scores, and nasal discharge weights, were also reduced by ruprintrivir
      treatment. Overall, ruprintrivir was well tolerated; blood-tinged mucus and nasal
      passage irritation were the most common adverse effects reported. Pharmacokinetic
      analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug
      residence with minimal systemic absorption. Results from these studies in
      experimental rhinoviral infection support continued investigation of intranasal
      ruprintrivir in the setting of natural HRV infection.

PMID- 14638502
TI  - Comparative drug disposition, urinary pharmacokinetics, and renal effects of
      multilamellar liposomal nystatin and amphotericin B deoxycholate in rabbits.
AB  - The comparative drug dispositions, urinary pharmacokinetics, and effects on renal
      function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B
      deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were
      determined by high-performance liquid chromatography as total concentrations of
      LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body
      weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in
      escalating maximum concentrations (Cmax) (17 to 56 microg/ml for LNYS versus 3.36
      microg/ml for DAMB; P<0.001) and values for the area under the concentration-time
      curve from 0 to 24 h (AUC(0-24)) (17 to 77 microg.h/ml for LNYS versus 12
      microg.h/ml for DAMB; P<0.001) in plasma but a significantly faster total
      clearance from plasma (0.117 to 0.080 liter/h/kg for LNYS versus 0.055 liter/h/kg
      for DAMB; P=0.013) and a < or =8-fold-smaller volume of distribution at steady
      state (P=0.002). Urinary drug concentration data revealed a > or =10-fold-higher
      Cmax (16 to 10 microg/ml for LNYS versus 0.96 microg/ml for DAMB; P=0.015) and a
      4- to 7-fold-greater AUC(0-24) (63 to 35 microg.h/ml for LNYS versus 8.9
      microg.h/ml for DAMB; P=0.015) following the administration of LNYS, with a dose
      dependent decrease in the dose-normalized AUC(0-24) in urine (P=0.001) and a
      trend toward a dose-dependent decrease in renal clearance. Except for the
      kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after
      dosing were severalfold lower than those after administration of DAMB (P, <0.002
      to <0.001). Less than 1% each of the total dose of LNYS was recovered from the
      kidneys, liver, spleen, and lungs; in contrast, a quarter of the total dose was
      recovered from the livers of DAMB-treated animals. LNYS had dose-dependent
      effects on glomerular filtration and distal, but not proximal, renal tubular
      function which did not exceed those of DAMB at the highest investigated dosage of
      6 mg/kg. The results of this experimental study demonstrate fundamental
      differences in the dispositions of LNYS and DAMB. Based on its enhanced urinary
      exposure, LNYS may offer a therapeutic advantage in systemic fungal infections
      involving the upper and lower urinary tracts that require therapy with antifungal
      polyenes.

PMID- 14638503
TI  - Evolutionary models of the emergence of methicillin-resistant Staphylococcus
      aureus.
AB  - Five major lineages of methicillin-resistant Staphylococcus aureus (MRSA) have
      evolved since the introduction of methicillin for the treatment of infections
      caused by penicillin-resistant S. aureus in 1959. The clones of these lineages
      are responsible for the vast majority of hospital-acquired MRSA disease globally.
      We have constructed high-resolution evolutionary models for each lineage using a
      parsimony approach with 15 partial gene sequences from 147 geographically diverse
      isolates. On the basis of these models, we infer that MRSA has emerged at least
      20 times upon acquisition of the methicillin resistance determinant, which is
      carried on a mobile genetic element called the staphylococcal cassette chromosome
      mec (SCCmec). The acquisition of SCCmec by sensitive clones was four times more
      common than the replacement of one SCCmec with another. Notably, SCCmec type IV
      was found in twice as many clones as any other SCCmec type, and it is this SCCmec
      type which is commonly found in clones from patients with community-acquired MRSA
      disease. Our findings suggest that most clones of MRSA arise by the acquisition
      of SCCmec type IV by methicillin-sensitive isolates.

PMID- 14638504
TI  - Pharmacodynamics of the new des-f(6)-quinolone garenoxacin in a murine thigh
      infection model.
AB  - Garenoxacin is a new des-F(6)-quinolone with broad-spectrum activity against both
      gram-positive cocci and gram-negative bacilli. We used the neutropenic murine
      thigh infection model to characterize the time course of antimicrobial activity
      of garenoxacin and determine which pharmacokinetic-pharmacodynamic (PK-PD)
      parameter best correlated with efficacy. Serum drug levels following three
      fourfold-escalating single-dose levels of garenoxacin were measured by
      microbiologic assay. In vivo postantibiotic effects (PAEs) were determined after
      doses of 16 and 64 mg/kg of body weight. Mice had 10(6.5) to 10(6.7) CFU of
      Streptococcus pneumoniae strain ATCC 10813 or Staphylococcus aureus strain ATCC
      33591 per thigh when they were treated for 24 h with garenoxacin at a dose of 4
      to 128 mg/kg/day fractionated for 3-, 6-, 12-, and 24-hour dosing regimens.
      Nonlinear regression analysis was used to determine which PK-PD parameter best
      correlated with the measurement of CFU/thigh at 24 h. Pharmacokinetic studies
      yielded peak/dose values of 0.2 to 0.3, area under the concentration-time curve
      (AUC)/dose values of 0.1 to 0.5, and half-lives of 0.7 to 1.6 h. Garenoxacin
      produced in vivo PAEs of 1.4 to 8.2 h with S. pneumoniae ATCC 10813, 7.6 to >12.4
      h with S. aureus ATCC 25923, and 0 to 1.5 h with Klebsiella pneumoniae ATCC
      43816. The 24-h AUC/MIC ratio was the PK-PD parameter that best correlated with
      efficacy (R2=71 to 90% for the two organisms compared with 43 to 56% for the
      peak/MIC ratio and 47 to 75% for percent time above the MIC [% T>MIC]). In
      subsequent studies we used the neutropenic murine thigh infection model to
      determine if the magnitude of the AUC/MIC ratio needed for efficacy of
      garenoxacin varied among pathogens (including resistant strains). Mice had
      10(5.9) to 10(7.2) CFU of 6 strains of S. aureus (2 methicillin resistant), 11
      strains of S. pneumoniae (5 penicillin susceptible, 1 penicillin intermediate,
      and 5 penicillin resistant, and of the resistant strains, 3 were also
      ciprofloxacin resistant), and 4 gram-negative strains per thigh when treated for
      24 h with 1 to 64 mg of garenoxacin per kg every 12 h. A sigmoid dose-response
      model was used to estimate the doses (mg/kg/24 h) required to achieve a net
      bacteriostatic effect over 24 h. MICs ranged from 0.008 to 4 microg/ml. The free
      drug 24-h AUC/MIC ratios for each static dose (2.8 to 128 mg/kg/day) varied from
      8.2 to 145. The mean 24-h AUC/MIC ratios +/- standard deviations for S.
      pneumoniae, S. aureus, and gram-negative strains were 33 +/- 18, 81 +/- 37, and
      33 +/- 30, respectively. Methicillin, penicillin, or ciprofloxacin resistance did
      not alter the magnitude of the AUC/MIC ratio required for efficacy.

PMID- 14638505
TI  - Single and double mutations in gyrA but not in gyrB are associated with low- and
      high-level fluoroquinolone resistance in Helicobacter pylori.
AB  - In one French hospital the rate of resistance to ciprofloxacin in Helicobacter
      pylori was 3.3% (2 of 60 strains) in 1999. The six resistant clinical strains
      (four from 1996 and two from 1999) and three ciprofloxacin-selected single-step
      mutants studied carried one gyrA mutation but none in gyrB. Clinafloxacin and
      garenoxacin were the most active fluoroquinolones against these mutants.
      Occurrence of a second gyrA mutation was associated with high MICs of all
      fluoroquinolones tested.

PMID- 14638506
TI  - Molecular epidemiology of orf513-bearing class 1 integrons in multiresistant
      clinical isolates from Argentinean hospitals.
AB  - The spread of orf513-bearing class 1 integrons is associated with bla(CTX-M-2) in
      gram-negative clinical isolates in Argentina, with In35 being the most frequently
      found integron (74%). Among 65 isolates without bla(CTX-M-2), only one harbored a
      novel orf513-bearing class 1 integron with the dfrA3b gene. The finding of orf513
      not associated with class 1 integrons in two gram-positive strains indicates the
      widespread occurrence of this putative site-specific recombinase.

PMID- 14638507
TI  - Structures, locations, and transfer frequencies of genetic elements conferring
      high-level gentamicin resistance in Enterococcus faecalis isolates in Greece.
AB  - The elements conferring high-level gentamicin resistance in 64 clinical isolates
      of Enterococcus faecalis were characterized by PCR and by restriction enzyme
      hybridization analysis of genomic and plasmid DNA. There was a strong association
      between gentamicin resistance and the aac(6')-aph(2") gene carried on IS256-based
      elements with different structures, locations, and transfer characteristics.

PMID- 14638508
TI  - Plasmid content of a vancomycin-resistant Enterococcus faecalis isolate from a
      patient also colonized by Staphylococcus aureus with a VanA phenotype.
AB  - Vancomycin-resistant Enterococcus faecalis coisolated with vancomycin-resistant
      (VanA) Staphylococcus aureus was found to contain two plasmids, designated pAM830
      (45 kb) and pAM831 (95 kb). pAM830, found to be conjugative and closely related
      to the Inc18 family of broad-host-range conjugative plasmids, encodes resistances
      to vancomycin (via a Tn1546-like element) and erythromycin; pAM831 encodes
      resistances to gentamicin, streptomycin, and erythromycin.

PMID- 14638509
TI  - Bactericidal activities of daptomycin, quinupristin-dalfopristin, and linezolid
      against vancomycin-resistant Staphylococcus aureus in an in vitro pharmacodynamic
      model with simulated endocardial vegetations.
AB  - In search of treatment alternatives against vancomycin-resistant S. aureus
      (VRSA), an in vitro pharmacodynamic model with simulated endocardial vegetations
      incorporating protein and a high inoculum was used to simulate daptomycin,
      linezolid, quinupristin-dalfopristin, and vancomycin against the Michigan VRSA
      strain. Daptomycin and quinupristin-dalfopristin exhibited the greatest bacterial
      reductions, and all tested agents except vancomycin exhibited bactericidal
      activity against the VRSA.

PMID- 14638510
TI  - Linezolid penetration into bone and joint tissues infected with methicillin
      resistant staphylococci.
AB  - Penetration of linezolid into bone and joint tissues was studied by high
      performance liquid chromatography in 13 patients suffering from implant
      associated infections with methicillin-resistant staphylococci. Mean
      concentrations of linezolid in infected tissues were greater than 10 mg/liter in
      a sampling time range of 35 to 124 min after administration of the preoperative
      dose, except in bone specimens, where they reached 3.9 +/- 2.0 mg/liter.

PMID- 14638511
TI  - In vitro activity of tigecycline against Staphylococcus epidermidis growing in an
      adherent-cell biofilm model.
AB  - The activity of tigecycline against Staphylococcus epidermidis growing in an in
      vitro adherent-cell biofilm model was determined. Tigecycline minimum
      bactericidal concentrations (MBCs) ranged from 1 to 8 microg/ml for S.
      epidermidis growing in a biofilm of adherent cells, compared to MBCs of 0.12 to
      >32 microg/ml for freely growing cells. The killing activity of tigecycline
      against the adherent bacteria was at least fourfold better than that of
      vancomycin and daptomycin.

PMID- 14638512
TI  - Mannosyl glycodendritic structure inhibits DC-SIGN-mediated Ebola virus infection
      in cis and in trans.
AB  - We have designed a glycodendritic structure, BH30sucMan, that blocks the
      interaction between dendritic cell-specific intercellular adhesion molecule 3
      grabbing nonintegrin (DC-SIGN) and Ebola virus (EBOV) envelope. BH30sucMan
      inhibits DC-SIGN-mediated EBOV infection at nanomolar concentrations. BH30sucMan
      may counteract important steps of the infective process of EBOV and, potentially,
      of microorganisms shown to exploit DC-SIGN for cell entry and infection.

PMID- 14638513
TI  - Comparative in vitro susceptibilities and bactericidal activities of
      investigational fluoroquinolone ABT-492 and other antimicrobial agents against
      human mycoplasmas and ureaplasmas.
AB  - We determined in vitro susceptibilities for ABT-492 and other antimicrobials
      against Mycoplasma pneumoniae, Mycoplasma fermentans, Mycoplasma hominis, and
      Ureaplasma species. ABT-492 MICs were < or =1 microg/ml, and the agent was
      bactericidal against selected isolates of M. pneumoniae and M. hominis. ABT-492
      has potential for treatment of infections due to these microorganisms.

PMID- 14638514
TI  - Efficacy of voriconazole in treatment of systemic scedosporiosis in neutropenic
      mice.
AB  - We have evaluated the efficacy of voriconazole (VRC) in a murine model of
      systemic infection by Scedosporium apiospermum. The survival of mice treated with
      VRC at 5, 20, or 40 mg/kg/day was greater than that of the control group (P< or
      =0.0009). VRC reduced the tissue burden in the spleen and brain (P<0.001 in both
      organs) in comparison with that of the control group.

PMID- 14638515
TI  - Genotypes of Pneumocystis jiroveci isolates obtained in Harare, Zimbabwe, and
      London, United Kingdom.
AB  - Isolates of Pneumocystis jiroveci from sulfa-exposed and nonexposed patients from
      London, United Kingdom, and Harare, Zimbabwe, were genotyped. At the
      dihydropteroate synthase (DHPS) locus, there was evidence of selection pressure
      from sulfa drug exposure, and reversal of DHPS genotype ratios occurred when
      selection pressure was absent or was removed.

PMID- 14638516
TI  - Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric
      xenografts implanted in nude mice.
AB  - Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate
      precursor in broccoli sprouts, has shown in vitro activity against Helicobacter
      pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by
      using human gastric xenografts in nude mice. H. pylori was completely eradicated
      in 8 of the 11 sulforaphane-treated grafts. This result suggests that
      sulforaphane might be beneficial in the treatment of H. pylori-infected
      individuals.

PMID- 14638517
TI  - In vitro susceptibility testing of Geotrichum capitatum: comparison of the E
      test, disk diffusion, and Sensititre colorimetric methods with the NCCLS M27-A2
      broth microdilution reference method.
AB  - The in vitro activities of amphotericin B, flucytosine, fluconazole,
      itraconazole, and voriconazole against 23 isolates of Geotrichum capitatum were
      determined by the National Committee for Clinical Laboratory Standards (NCCLS)
      M27-A2 microdilution method and the Sensititre and agar diffusion methods.
      Amphotericin B and voriconazole appeared to be the more active drugs. Sensititre
      showed the highest rates of agreement with the NCCLS M27-A2 method.

PMID- 14638518
TI  - Prevalence of extended-spectrum beta-lactamase-producing Enterobacter cloacae in
      the Asia-Pacific region: results from the SENTRY Antimicrobial Surveillance
      Program, 1998 to 2001.
AB  - Enterobacter cloacae strains from hospitalized patients with a range of
      infections were collected by 17 laboratories in the Asia-Pacific region and South
      Africa. Isolates for which ceftriaxone MICs were above 1 microg/ml and/or
      ceftazidime MICs were above 2 microg/ml, as well as 46 strains for which
      ceftriaxone and/or ceftazidime MICs were at or below these values, were screened
      for levels of extended-spectrum beta-lactamase (ESBL) production through the use
      of broth microdilution for the detection of clavulanate enhancement of the
      activity of ceftriaxone, ceftazidime, and cefepime. Of the isolates examined,
      ceftriaxone and/or ceftazidime had elevated MICs for 44%, of which 36% were ESBL
      positive. ESBL-positive strains were commonly susceptible to piperacillin
      tazobactam and more frequently resistant to several other antimicrobials studied.
      A cefepime MIC above 0.25 microg/ml had the highest sensitivity (100%) and
      specificity (74%) for predicting the presence of an ESBL.

PMID- 14638519
TI  - Extended-spectrum beta-lactamase TEM-24 in an Aeromonas clinical strain:
      acquisition from the prevalent Enterobacter aerogenes clone in France.

PMID- 14638520
TI  - Susceptibilities of fluoroquinolone-resistant Haemophilus parainfluenzae isolates
      from Japanese patients with respiratory infections to five fluoroquinolones and
      other antimicrobial agents.

PMID- 14638521
TI  - Unambiguous numbering of antibiotic resistance genes.

PMID- 14638522
TI  - Cardiac resynchronization therapy for heart failure.

PMID- 14638523
TI  - Should evidence-based proof of efficacy as defined for a specific therapeutic
      agent be extrapolated to encompass a therapeutic class of agents?

PMID- 14638524
TI  - Should evidence-based proof of drug efficacy be extrapolated to a "class of
      agents"?

PMID- 14638525
TI  - Therapeutic substitution: guilty until proven innocent.

PMID- 14638527
TI  - Images in cardiovascular medicine. Giant left atrial aneurysm in a 15-month-old
      child.

PMID- 14638526
TI  - Clinician guide to angiogenesis.

PMID- 14638529
TI  - Images in cardiovascular medicine. Neointimal hyperplasia in carotid stent
      detected with multislice computed tomography.

PMID- 14638530
TI  - Uric acid and prognosis in chronic heart failure.

PMID- 14638531
TI  - Genetics and susceptibility of coronary collateral formation.

PMID- 14638532
TI  - Endothelial progenitor cells: mainly derived from the monocyte/macrophage
      containing CD34- mononuclear cell population and only in part from the
      hematopoietic stem cell-containing CD34+ mononuclear cell population.

PMID- 14638533
TI  - Statins and incidence of perioperative mortality in patients undergoing major
      noncardiac vascular surgery.

PMID- 14638534
TI  - Serum total cholesterol concentrations and awareness, treatment, and control of
      hypercholesterolemia among US adults.

PMID- 14638535
TI  - Sudden cardiac death among women in the United States.

PMID- 14638536
TI  - Detecting vulnerable plaque.

PMID- 14638537
TI  - Overweight children.

PMID- 14638538
TI  - Blood pressure, C-reactive protein, and risk of future cardiovascular events.
AB  - BACKGROUND: Accumulating data suggest a link between blood pressure and vascular
      inflammation. METHODS AND RESULTS: We examined the relationship between blood
      pressure, C-reactive protein (CRP), and incident first cardiovascular events
      among 15 215 women followed prospectively over a median of 8.1 years. In cross
      sectional analyses at baseline, median levels of CRP for women with blood
      pressure <120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94,
      and > or =160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively
      (P for trend <0.0001). Increasing categories of blood pressure were significant
      predictors of CRP levels at baseline. In prospective analyses, both elevated CRP
      levels (> or =3 mg/L) and increasing categories of blood pressure were
      independent determinants of future cardiovascular events, and CRP had incremental
      prognostic value at all levels of blood pressure. The adjusted hazard ratio for
      women with blood pressure > or =160/95 mm Hg and CRP levels > or =3 mg/L was 8.31
      (95% CI, 4.44 to 15.55, P<0.0001) compared with those with blood pressure <120/75
      and CRP levels <3 mg/L. After participants had been divided into 4 groups on the
      basis of CRP levels (<3 or > or =3 mg/L) and blood pressure levels (<130/85 or >
      or =130/85), the risk factor-adjusted hazard ratios were as follows: low CRP/low
      blood pressure, 1.0; high CRP/low blood pressure, 1.87 (P=0.002); low CRP/high
      blood pressure, 2.54 (P<0.0001); and high CRP/high blood pressure, 3.27
      (P<0.0001). CONCLUSIONS: CRP and blood pressure are independent determinants of
      cardiovascular risk, and their predictive value is additive.

PMID- 14638539
TI  - Cyclooxygenase isoforms and platelet vessel wall interactions in the
      apolipoprotein E knockout mouse model of atherosclerosis.
AB  - BACKGROUND: Cyclooxygenase (COX) activity is induced in human atherosclerosis,
      and the products formed may modify the disease directly or through an effect on
      platelets. We examined the role of COX-1 and -2 on platelet vessel wall
      interactions and development of atherosclerosis in a murine model. METHODS AND
      RESULTS: Apolipoprotein E-deficient (apoE-/-) mice fed a 1% cholesterol diet were
      treated with a selective COX-1 inhibitor (SC-560), a selective COX-2 inhibitor
      (SC-236), or vehicle. Urinary prostacyclin and thromboxane metabolites (2,3-dinor
      6-keto-PGF1alpha and 2,3-dinor-TXB2) were increased in the apoE-/- knockout
      mouse. There was also induction of both COX isoforms in the vascular lesions
      formed, which stained for CD41, a platelet-specific marker, and for CD40L.
      Selective inhibition of COX-2 had no effect on lesion formation and, despite
      selective reduction in prostacyclin generation, had no effect on platelet
      activity, as measured by thromboxane formation or platelet deposition. Selective
      inhibition of COX-1 reduced 2,3-dinor-TXB2 generation and lesion formation.
      However, platelet deposition on the vessel wall persisted, with well-defined
      monolayers seen. There was also persistent expression of the macrophage marker
      CD68 and increased expression of the cell death protein Bax. In contrast to
      lesion development, the selective COX-1 inhibitor had no effect on the regression
      of evolving lesions. CONCLUSIONS: COX-1 plays an important role in the early
      stages of lesion development in the apoE-/- knockout model of atherosclerosis,
      preventing gross lesion formation in the face of continued vascular injury and
      inflammation. Despite the inhibition of prostacyclin, COX-2 inhibition had no
      effect on lesion development or platelet-vessel wall interactions.

PMID- 14638540
TI  - Identification of alpha-chloro fatty aldehydes and unsaturated
      lysophosphatidylcholine molecular species in human atherosclerotic lesions.
AB  - BACKGROUND: A role for myeloperoxidase (MPO) as a mediator of coronary artery
      disease and acute coronary syndromes has recently received considerable
      attention. Although active MPO and hypochlorite-modified proteins and peptides
      have been detected in human atherosclerotic lesions, detection of novel
      chlorinated oxidized lipid species with proatherogenic properties in vivo has not
      yet been reported. In this study we show that MPO-generated reactive chlorinating
      species promote selective oxidative cleavage of plasmalogens, liberating alpha
      chloro fatty aldehydes and unsaturated lysophosphatidylcholine in human
      atherosclerotic lesions. METHODS AND RESULTS: Stable isotope dilution gas
      chromatography-mass spectrometry methods were used to identify and quantitate the
      alpha-chloro fatty aldehyde, 2-chlorohexadecanal, in atherosclerotic versus
      normal human aorta. Compared with normal aorta, 2-chlorohexadecanal levels were
      elevated more than 1400-fold in atherosclerotic tissues. Parallel electrospray
      ionization mass spectrometry studies confirmed 34- and 20-fold increases in the
      plasmalogen cooxidation products, unsaturated lysophosphatidylcholine molecular
      species containing linoleic and arachidonic acid, respectively, within
      atherosclerotic compared with normal aorta. Unsaturated lysophosphatidylcholine
      containing docosahexaenoic acid was also detected in atherosclerotic but not in
      normal aorta. Exposure of primary human coronary artery endothelial cells to
      plasmalogen-derived lysophosphatidylcholine molecular species produced marked
      increases in P-selectin surface expression. CONCLUSIONS: The present studies
      demonstrate that plasmalogens are attacked by MPO-derived reactive chlorinating
      species within human atheroma. The resultant species formed, alpha-chloro fatty
      aldehydes and unsaturated lysophospholipids, possess proatherogenic properties,
      as shown by induction of P-selectin surface expression in primary human coronary
      artery endothelial cells.

PMID- 14638541
TI  - Missense mutations and gene interruption in PROSIT240, a novel TRAP240-like gene,
      in patients with congenital heart defect (transposition of the great arteries).
AB  - BACKGROUND: Congenital heart disease represents the most common severe birth
      defect, affecting 0.7% to 1% of all neonates, among whom 5% to 7% display
      transposition of the great arteries (TGA). TGA represents a septation defect of
      the common outflow tract of the heart, manifesting around the fifth week during
      embryonic development. Despite its high prevalence, very little is known about
      the pathogenesis of this disease. METHODS AND RESULTS: Using a positional cloning
      approach, we isolated a novel gene, PROSIT240 (also termed THRAP2), that is
      interrupted in a patient with a chromosomal translocation and who displays TGA
      and mental retardation. High expression of PROSIT240 within the heart (aorta) and
      brain (cerebellum) was well correlated with the malformations observed in the
      patient and prompted further analyses. PROSIT240 shows significant homology to
      the nuclear receptor coactivator TRAP240, suggesting it to be a new component of
      the thyroid hormone receptor-associated protein (TRAP) complex. Interestingly,
      several TRAP components have been previously shown to be important in early
      embryonic development in various organisms, making PROSIT240 an excellent
      candidate gene to be correlated to the patient's phenotype. Subsequent mutational
      screening of 97 patients with isolated dextro-looped TGA revealed 3 missense
      mutations in PROSIT240, which were not detected in 400 control chromosomes.
      CONCLUSIONS: Together, these genetic data suggest that PROSIT240 is involved in
      early heart and brain development.

PMID- 14638542
TI  - Long-term follow-up of incomplete stent apposition in patients who received
      sirolimus-eluting stent for de novo coronary lesions: an intravascular ultrasound
      analysis.
AB  - BACKGROUND: Incomplete stent apposition (ISA) has been previously documented
      after sirolimus-eluting stent (SES) implantation. The aim of this study was to
      investigate the long-term intravascular ultrasound (IVUS) findings of ISA in
      patients who received SES. METHODS AND RESULTS: A total of 13 patients who
      received SES and showed ISA at follow-up IVUS (follow-up I) were investigated.
      IVUS was performed on all of these patients 12 months later (follow-up II).
      Quantitative ISA area measurement was also performed at follow-up I and II. No
      vascular remodeling was observed in the vessel segment with ISA; external elastic
      membrane area was 19.4+/-6.6 versus 19.5+/-6.4 mm2 at follow-up I and II,
      respectively. There was also no significant change in external elastic membrane
      area between vessel segment with ISA and without ISA (+1.5% versus -3.0%,
      respectively; P=0.27) at late follow-up. The ISA area, either including (2.5+/
      1.7 versus 3.8+/-6.3 mm2; P=NS) or excluding (2.5+/-1.8 versus 2.4+/-1.7 mm2;
      P=NS) a single patient with aneurysm formation, was not significantly different
      between follow-up I and II. One patient manifested a coronary aneurysm in the
      stented segment at late follow-up that was probably present at the initial follow
      up but masked by thrombus. It was successfully treated with a covered stent. All
      patients were asymptomatic, and no patient experienced late thrombotic occlusion.
      CONCLUSIONS: Vessel dimensions and area of ISA did not change over time, except
      for 1 coronary aneurysm that became apparent. ISA after implantation of a SES was
      not associated with adverse events at late follow-up.

PMID- 14638543
TI  - Noninvasive evaluation of coronary reperfusion by transthoracic Doppler
      echocardiography in patients with anterior acute myocardial infarction before
      coronary intervention.
AB  - BACKGROUND: Transthoracic Doppler echocardiography (TTDE) enables evaluation of
      distal left anterior descending coronary artery (LAD) flow. The purpose of this
      study was to test whether TTDE can differentiate coronary reperfusion with
      Thrombolysis in Myocardial Infarction (TIMI) grade 3 from TIMI grade < or =2 in
      patients with anterior acute myocardial infarction (AMI). METHODS AND RESULTS: In
      46 consecutive patients with a first anterior AMI in the acute phase before
      emergent coronary intervention, the presence of antegrade distal LAD flow and its
      diastolic peak velocity were evaluated by color and pulsed TTDE and compared with
      TIMI grades by subsequent coronary angiography performed 29+/-12 minutes later.
      Nineteen patients had TIMI 0 reperfusion, 4 had TIMI 1, 10 had TIMI 2, and 13 had
      TIMI 3. Visual antegrade distal LAD flow was present in 22 of the 46 patients.
      TIMI 2 and 3 reperfusions were both generally visualized by color TTDE. However,
      peak distal LAD flow velocity by pulsed TTDE was significantly greater in
      patients with TIMI 3 compared with those with TIMI 2 (40+/-10 vs 20+/-6 cm/s,
      P<0.0001). The diagnosis of TIMI 3 based on diastolic peak distal LAD flow
      velocity > or =25 cm/s by TTDE had a sensitivity, specificity, and accuracy of
      77%, 94%, and 89%, respectively. CONCLUSIONS: TTDE enables noninvasive
      differentiation of TIMI 3 from TIMI < or =2 coronary reperfusion in patients with
      AMI in the acute phase before emergent coronary intervention.

PMID- 14638544
TI  - Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish
      patients from control subjects better than high-density lipoprotein cholesterol
      levels and are favorably affected by simvastatin treatment.
AB  - BACKGROUND: The inflammatory/antiinflammatory properties of HDL were compared
      with HDL cholesterol in 2 groups of patients and in age- and sex-matched control
      subjects. METHODS AND RESULTS: Group 1 consisted of 26 patients not yet taking a
      statin who presented with coronary heart disease (CHD) or CHD equivalents by
      National Cholesterol Education Program Adult Treatment Panel III criteria studied
      before and 6 weeks after 40 mg/d of simvastatin. Group 2 consisted of 20 patients
      with documented CHD and HDL cholesterol > or =84 mg/dL. The
      inflammatory/antiinflammatory properties of HDL were determined by the ability of
      the subject's HDL to alter LDL-induced monocyte chemotactic activity (MCA) in a
      human artery wall coculture. Induction of MCA by a control LDL was determined in
      the absence or presence of the subject's HDL. Values in the absence of HDL were
      normalized to 1.0. Values >1.0 after the addition of HDL indicated
      proinflammatory HDL; values <1.0 indicated antiinflammatory HDL. Group 1 values
      before simvastatin were LDL cholesterol, 118+/-24 mg/dL; HDL cholesterol, 57+/-13
      mg/dL; triglycerides, 125+/-64 mg/dL; and high-sensitivity C-reactive protein (hs
      CRP), 1.7+/-1.9 mg/L; and MCA values were 1.38+/-0.91, compared with 0.38+/-0.14
      for control subjects (P=1.5x10(-5)). After simvastatin, values were LDL
      cholesterol, 73+/-24 mg/dL; HDL cholesterol, 61+/-14 mg/dL; triglycerides, 99+/
      52 mg/dL; and hs-CRP, 1.3+/-1.3 mg/L; and MCA values were 1.08+/-0.71. In group
      2, values were LDL cholesterol, 108+/-34 mg/dL; HDL cholesterol, 95+/-14 mg/dL;
      triglycerides, 89+/-44 mg/dL; and hs-CRP, 0.8+/-0.7 mg/L; and MCA values were
      1.28+/-0.29, compared with 0.35+/-0.11 for control subjects (P=1.7x10(-14)).
      Similar results were obtained with the cell-free assay. CONCLUSIONS: The
      inflammatory/antiinflammatory properties of HDL distinguished patients from
      control subjects better than HDL cholesterol and were improved with simvastatin.

PMID- 14638545
TI  - Impact of renal insufficiency in patients undergoing primary angioplasty for
      acute myocardial infarction.
AB  - BACKGROUND: The prognostic importance of renal insufficiency (RI) in patients
      undergoing primary percutaneous coronary intervention (PCI) for acute myocardial
      infarction (AMI) has not been well characterized. METHODS AND RESULTS: PCI was
      performed in 2082 AMI patients without shock presenting within 12 hours of
      symptom onset in a prospective, multicenter randomized trial. RI was defined as a
      calculated (Cockroft-Gault) creatinine clearance (CrCl) < or =60 mL/min. RI at
      baseline was present in 18% of patients. Compared with patients without RI,
      patients with RI were older and were more likely to be female; to have
      hypertension, peripheral vascular disease, or cerebrovascular disease; and to
      present in heart failure. Mortality was markedly increased in patients with
      versus without baseline RI both at 30 days (7.5% versus 0.8%, P<0.0001) and at 1
      year (12.7% versus 2.4%, P<0.0001). Mortality rates increased incrementally for
      every 10-mL/min decrease in baseline CrCl. By multivariate analysis, reduced
      baseline CrCl was a powerful independent predictor of 30-day mortality (hazard
      ratio, 5.77; P<0.0001) and remained associated with reduced survival at 1 year
      (hazard ratio, 1.98; P=0.08). Hemorrhagic complications and transfusion
      requirements were also increased more than 2-fold in patients with RI, as were
      severe restenosis (diameter stenosis > or =70%; 20.6% versus 11.8%, P=0.024) and
      infarct artery reocclusion (14.7% versus 7.3%, P=0.02). CONCLUSIONS: Baseline RI
      in patients with AMI undergoing primary PCI is associated with a markedly
      increased risk of mortality, as well as bleeding and restenosis. Novel approaches
      are needed to improve the otherwise poor prognosis of patients with RI and AMI.

PMID- 14638546
TI  - Implantable cardioverter-defibrillator therapy for prevention of sudden death in
      patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is
      a condition associated with the risk of sudden death (SD). METHODS AND RESULTS:
      We conducted a multicenter study of the impact of the implantable cardioverter
      defibrillator (ICD) for prevention of SD in 132 patients (93 males and 39
      females, age 40+/-15 years) with ARVC/D. Implant indications were a history of
      cardiac arrest in 13 patients (10%), sustained ventricular tachycardia in 82
      (62%), syncope in 21 (16%), and other in 16 (12%). During a mean follow-up of
      39+/-25 months, 64 patients (48%) had appropriate ICD interventions, 21 (16%) had
      inappropriate interventions, and 19 (14%) had ICD-related complications. Fifty
      three (83%) of the 64 patients with appropriate interventions received
      antiarrhythmic drug therapy at the time of first ICD discharge. Programmed
      ventricular stimulation was of limited value in identifying patients at risk of
      tachyarrhythmias during the follow-up (positive predictive value 49%, negative
      predictive value 54%). Four patients (3%) died, and 32 (24%) experienced
      ventricular fibrillation/flutter that in all likelihood would have been fatal in
      the absence of the device. At 36 months, the actual patient survival rate was 96%
      compared with the ventricular fibrillation/flutter-free survival rate of 72%
      (P<0.001). Patients who received implants because of ventricular tachycardia
      without hemodynamic compromise had a significantly lower incidence of ventricular
      fibrillation/flutter (log rank=0.01). History of cardiac arrest or ventricular
      tachycardia with hemodynamic compromise, younger age, and left ventricular
      involvement were independent predictors of ventricular fibrillation/flutter.
      CONCLUSIONS: In patients with ARVC/D, ICD therapy provided life-saving protection
      by effectively terminating life-threatening ventricular arrhythmias. Patients who
      were prone to ventricular fibrillation/flutter could be identified on the basis
      of clinical presentation, irrespective of programmed ventricular stimulation
      outcome.

PMID- 14638547
TI  - Milrinone facilitates resuscitation from cardiac arrest and attenuates
      postresuscitation myocardial dysfunction.
AB  - BACKGROUND: Left ventricular (LV) dysfunction with a low cardiac index after
      successful CPR contributes to early death attributable to multiorgan failure, and
      an effective treatment has not been identified. The purpose of this study was to
      investigate the use of milrinone, a selective phosphodiesterase III inhibitor, as
      treatment for LV dysfunction after resuscitation. METHODS AND RESULTS:
      Ventricular fibrillation (VF) was induced electrically in 32 swine. After 5
      minutes of VF, CPR was initiated and animals were randomized to receive either
      saline (control group, n=16) as a bolus and infusion or milrinone 50 microg/kg as
      a bolus and then 0.5 microg/kg per min for 60 minutes (treatment group, n=16).
      After 2 minutes of CPR (total VF time, 7 minutes), countershocks were given.
      Coronary perfusion pressures during CPR were similar for the groups (24+/-2
      versus 21+/-4 mm Hg). All animals were defibrillated; 6 of 16 control animals
      developed refractory postcountershock pulseless electrical activity compared with
      0 of 16 treated animals (P=0.018). At 30 minutes after restoration of spontaneous
      circulation, stroke volume (16+/-3 versus 26+/-7 mL, P<0.01) and LV dp/dt (793+/
      197 versus 1108+/-316 mm Hg/s, P<0.02) were higher in the treatment group.
      Similar differences were observed 60 minutes after restoration of spontaneous
      circulation. Significant differences in heart rates between groups were not
      observed, and peripheral vascular resistance was significantly greater in the
      control group 30 and 60 minutes after resuscitation. CONCLUSIONS: Milrinone
      facilitates resuscitation from prolonged VF and attenuates LV dysfunction after
      resuscitation without worsening major determinants of myocardial oxygen demand.

PMID- 14638548
TI  - Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: genetic
      and physiological evidence.
AB  - BACKGROUND: NO is a major regulator of cardiovascular physiology that reduces
      vascular and cardiac contractility. Accumulating evidence indicates that
      endogenous inhibitors may regulate NOS. The NOS inhibitors asymmetric
      dimethylarginine (ADMA) and N-monomethylarginine are metabolized by the enzyme
      dimethylarginine dimethylaminohydrolase (DDAH). This study was designed to
      determine if increased expression of DDAH could reduce tissue and plasma levels
      of the NOS inhibitors and thereby increase NO synthesis. METHODS AND RESULTS: We
      used gene transfer and transgenic approaches to overexpress human DDAH I in vitro
      and in vivo. The overexpression of DDAH in cultured endothelial cells in vitro
      induced a 2-fold increase in NOS activity and NO production. In the hDDAH-1
      transgenic mice, we observed approximately 2-fold increases in tissue NOS
      activity and urinary nitrogen oxides, associated with a 2-fold reduction in
      plasma ADMA. The systolic blood pressure of transgenic mice was 13 mm Hg lower
      than that of wild-type controls (P<0.05). The systemic vascular resistance and
      cardiac contractility were decreased in response to the increase in NO
      production. CONCLUSIONS: DDAH I overexpression increases NOS activity in vitro
      and in vivo. The hDDAH-1 transgenic animal exhibits a reduced systolic blood
      pressure, systemic vascular resistance, and cardiac stroke volume. This study
      provides compelling evidence that the elaboration and metabolism of endogenous
      ADMA plays an important role in regulation of NOS activity.

PMID- 14638549
TI  - Inhibition of cardiac myocyte apoptosis improves cardiac function and abolishes
      mortality in the peripartum cardiomyopathy of Galpha(q) transgenic mice.
AB  - BACKGROUND: Although the occurrence of cardiac myocyte apoptosis during heart
      failure has been documented, its importance in pathogenesis is unknown.
      Transgenic mice with cardiac-restricted overexpression of Galpha(q) exhibit a
      lethal, peripartum cardiomyopathy accompanied by apoptosis. To test whether
      apoptosis is causally linked to heart failure, we assessed whether inhibiting
      this cell death would improve left ventricular function and survival in the
      Galpha(q) peripartum cardiomyopathy model. METHODS AND RESULTS: The potent
      polycaspase inhibitor IDN-1965 or vehicle was administered subcutaneously to
      Galpha(q) mice by osmotic minipump beginning on day 12 of pregnancy and
      continuing through euthanasia at day 14 postpartum. As expected, IDN-1965
      markedly suppressed cardiac caspase-3-like activity (86.5%; P<0.01), accompanied
      by reduction in the frequency of cardiac myocyte apoptosis from 1.9+/-0.3% to
      0.2+/-0.1% (P<0.01). Animals receiving IDN-1965 exhibited significant
      improvements in left ventricular end-diastolic dimension (vehicle, 4.7+/-0.1 mm;
      IDN-1965, 4.2+/-0.1 mm; P<0.01), fractional shortening (vehicle, 30.7+/-1.2%; IDN
      1965, 38.9+/-1.0%; P<0.01), positive (vehicle, 3972+/-412; IDN-1965, 5870+/-295;
      P<0.01) and negative (vehicle, 2365+/-213; IDN-1965, 3413+/-201; P<0.01) dP/dt,
      and complete suppression of mortality (vehicle, 6 of 20 died; IDN-1965, 0 of 14
      died; P<0.05). CONCLUSIONS: Reduction in cardiac myocyte apoptosis by caspase
      inhibition improved left ventricular function and survival in pregnant Galpha(q)
      mice. These data indicate that cardiac myocyte apoptosis plays a causal role in
      the pathogenesis of cardiomyopathy in this model. Caspase inhibition may provide
      a novel therapeutic target for heart failure.

PMID- 14638550
TI  - Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth
      muscle cells and a rat vascular smooth muscle cell line, A7r5.
AB  - BACKGROUND: We studied the growth-promoting effects of 2 sodium pump-selective
      cardiotonic steroids, ouabain and marinobufagenin, on cultured cells from
      vascular smooth muscle (VSMCs) from human umbilical vein and a rat VSMC line,
      A7r5. METHODS AND RESULTS: Both ouabain and marinobufagenin activated
      proliferation of these cells in a concentration-dependent manner, reflecting the
      cardiotonic steroid sensitivity of the specific alpha1 subunit contained within
      each cell source. The observed effective concentration ranges of both compounds
      was below that necessary to induce cytoplasmic ion alterations by sodium pump
      inhibition. CONCLUSIONS: These data indicate that the ouabain-activated
      proliferative effect previously observed in canine VSMCs occurs in other VSMC
      sources. This growth effect seems to be initiated by drug interaction with the
      sodium pump, reflected by the affinity of the steroid for the pump, and is
      independent of altered transmembrane ionic gradients.

PMID- 14638551
TI  - Adenovirus-mediated gene transfer of transforming growth factor-beta3, but not
      transforming growth factor-beta1, inhibits constrictive remodeling and reduces
      luminal loss after coronary angioplasty.
AB  - BACKGROUND: Extracellular matrix (ECM) remodeling is central to the development
      of restenosis after PTCA. Substantial evidence implicates transforming growth
      factor-beta1 (TGF-beta1), a regulator of ECM deposition by vascular cells, in its
      pathogenesis. TGF-beta3 reduces TGF-beta1-induced ECM deposition in cutaneous
      wounds. We therefore investigated the effects of intracoronary expression of TGF
      beta3 and TGF-beta1 on luminal loss after angioplasty. METHODS AND RESULTS:
      Porcine coronary arteries received an adenovirus expressing TGF-beta3, TGF-beta1,
      or lacZ (beta-galactosidase), or PBS only, at the site of angioplasty.
      Morphometric analysis 28 days after angioplasty confirmed reduced luminal loss in
      TGF-beta3 vessels (-0.65+/-0.10 mm2) compared with lacZ (-1.18+/-0.19 mm2) or PBS
      only (-1.19+/-0.17 mm2; P=0.003). Luminal loss was not reduced in TGF-beta1
      vessels (-1.02+/-0.19 mm2; P=0.48). An increase in the external elastic lamina
      area in TGF-beta3-treated vessels (+0.73+/-0.32 mm2) contrasted with decreases in
      control vessels (mean, -0.53+/-0.17 mm2; P=0.001) and TGF-beta1 vessels (-0.87+/
      0.34 mm2; P=0.003). Collagen content increased at the site of injury in TGF-beta3
      treated vessels (26.1+/-14.2%) but decreased in the lacZ (-22.8+/-6.6%) and PBS
      only (-23.4+/-7.0%; P=0.002) groups and was not significantly changed in TGF
      beta1-treated vessels. CONCLUSIONS: Expression of TGF-beta3 inhibits constrictive
      remodeling after PTCA and reduces luminal loss. This is accompanied by increased
      adventitial collagen, which may act as an external "scaffold" preventing vessel
      constriction. These findings confirm the potential of gene therapies that modify
      ECM remodeling for prophylaxis of restenosis.

PMID- 14638552
TI  - Robust adenoviral and adeno-associated viral gene transfer to the in vivo murine
      heart: application to study of phospholamban physiology.
AB  - BACKGROUND: Viral gene transfer to the whole heart in vivo has been achieved in
      several mammalian species but remained difficult to accomplish in murine hearts.
      We postulated that a key impediment derives from the use of proximal aortic
      occlusion during virus injection, because this eliminates coronary perfusion
      gradients in mice as aortic root and left ventricle pressures equalize. METHODS
      AND RESULTS: Pressure-volume analysis confirmed these mechanics. In contrast,
      descending aortic occlusion with whole-body cooling (20 degrees C) preserved
      transmyocardial perfusion gradients and allowed for sustained (>10-minute) dwell
      times in an upper-body perfusion circuit. This approach yielded robust cardiac
      transfection with adenovirus (AdV) and adeno-associated virus (AAV) injected into
      the left ventricle cavity or more simply via a central vein. Cardio-specific
      expression was achieved with a myocyte-specific promotor. Optimal AdV
      transfection required 9-minute aortic occlusion, versus 5-minute occlusion for
      AAV. Using this method, we examined the in vivo function of phospholamban (PLB)
      by stably transfecting PLB-null mice with AAV encoding PLB (AAV(PLB)). AAV(PLB)
      restored PLB protein to near control levels that colocalized with SERCA2A in
      cardiomyocytes. At baseline, PLB-null hearts exhibited enhanced systolic and
      diastolic function, but frequency-dependent reserve was blunted versus wild-type
      controls. These properties, particularly the frequency response, returned toward
      control 3 months after AAV(PLB) transfection. CONCLUSIONS: The new simplified
      approach for murine whole-heart viral transfection should assist molecular
      physiology studies.

PMID- 14638554
TI  - The quest for nursing home quality: learning history's lessons.
AB  - Nursing homes are arguably the most criticized sector of the US health care
      system. In fact, the nursing home industry's entire history has been marked by
      cycles of public clamor for improvement and ineffective governmental responses.
      Over the past century, multiple attempts to improve the quality of nursing home
      care have had limited success. This article reviews these initiatives from the
      era of the poorhouse to the most recent reform law, implemented during the last
      decade. An analysis suggests that the historical reliance on government
      regulation has not ensured nursing home quality. Future efforts should address
      the most glaring weaknesses of nursing home regulation, including the lack of
      standardization of the survey and enforcement processes. In addition, new
      strategies are needed beyond a reformed inspection system. This article
      demonstrates that while the exact path to nursing home quality is somewhat
      uncertain, retracing history's steps will not lead nursing homes in the desired
      direction.

PMID- 14638553
TI  - Activation of apoptosis signal-regulating kinase 1 in injured artery and its
      critical role in neointimal hyperplasia.
AB  - BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1), recently identified as
      one of the mitogen-activated protein kinase kinase kinases, is activated by
      various extracellular stimuli and involved in a variety of cellular function.
      Therefore, we first examined the role of ASK1 in vascular remodeling. METHODS AND
      RESULTS: We used rat balloon injury model and cultured vascular smooth muscle
      cells (VSMCs). Arterial ASK1 activity was rapidly and dramatically increased
      after balloon injury. To specifically inhibit endogenous ASK1 activation,
      dominant-negative mutant of ASK1 (DN-ASK1) was transfected into rat carotid
      artery before balloon injury. Gene transfer of DN-ASK1 significantly prevented
      neointimal formation at 14 days after injury. Bromodeoxyuridine labeling index at
      7 days after injury showed that DN-ASK1 remarkably suppressed VSMC proliferation
      in both the intima and the media. We also examined the role of ASK1 in cultured
      rat VSMCs. Infection with DN-ASK1 significantly attenuated serum-induced VSMC
      proliferation and migration. We also compared neointimal formation after cuff
      placement around the femoral artery between mice deficient in ASK1 (ASK1-/- mice)
      and wild-type (WT) mice. Neointimal formation at 28 days after cuff injury in
      ASK1-/- mice was significantly attenuated compared with WT mice. Furthermore, we
      compared the proliferation and migration of VSMCs isolated from ASK1-/- mice with
      WT mice. Both proliferation and migration of VSMCs from ASK1-/- mice were
      significantly attenuated compared with VSMCs from WT mice. CONCLUSIONS: ASK1
      activation plays the key role in vascular intimal hyperplasia. ASK1 may provide
      the basis for the development of new therapeutic strategy for vascular diseases.

PMID- 14638555
TI  - Do thiazide diuretics confer specific protection against strokes?
AB  - Several large studies have suggested that therapy with thiazide diuretics confers
      a particular benefit in reducing the risk of strokes that seem to be, at least to
      some extent, independent of the blood pressure-lowering effect. Such a
      cerebroprotective effect was documented not only with monotherapy but also when
      diuretics were used in combination with other drugs. The cerebroprotective effect
      does not seem to be shared by other drug classes, such as the beta-blockers or
      the angiotensin-converting enzyme inhibitors, in patients without manifest
      cardiovascular disease. Since stroke is one of the most devastating sequelae of
      high blood pressure, our data strongly favor the use of low-dose diuretics either
      as initial therapy or in combination in all hypertensive patients at risk for
      cerebrovascular disease.

PMID- 14638556
TI  - Physical activity and functional status in community-dwelling older women: a 14
      year prospective study.
AB  - BACKGROUND: Short-term prospective studies have shown physical activity to be
      related to functional status. To our knowledge, the association between physical
      activity levels and functional status over a longer period has not been
      established. METHODS: Two hundred twenty-nine older women (mean age, 74.2 years)
      who were involved in a randomized controlled walking intervention from 1982 to
      1985 were subsequently followed up until December 1999. Physical activity was
      assessed in 1985, 1995, and 1999 using a physical activity questionnaire and a
      physical activity monitor. In 1999, functional status was assessed by self-report
      and performance-based measures. RESULTS: Subjective and objective measures of
      physical activity in 1985 independently predicted gait speed in 1999 after
      controlling for age, chronic conditions, and activity limitation (subjective
      model-adjusted R2 = 0.09 [P=.03]; and objective model-adjusted R2 = 0.13
      [P=.008]). The consistency of physical activity participation from 1985 to 1995
      was also related to functional status in 1999. Women who were always active had
      the best functional status and women who were always inactive had the worst
      functional status. For difficulty with activities of daily living: those always
      active, 17 (37.8%) of 45 women; those inconsistently active, 24 (40.0%) of 60
      women; and those always inactive, 39 (59.1%) of 66 women (chi2 for trend P=.02).
      For score on the Physical Performance Test: those always active, 24.9; those
      inconsistently active, 24.5; and those always inactive, 23.8 (analysis of
      variance with linear contrasts P=.04). For gait speed: those always active, 1.17
      m/s; those inconsistently active, 1.15 m/s; and those always inactive, 1.03 m/s
      (analysis of variance with linear contrasts P=.002). CONCLUSION: We demonstrated
      a significant relation between physical activity during a 14-year period and
      current functional status in older women, thus suggesting that physical activity
      plays a role in maintaining functional ability later in life.

PMID- 14638557
TI  - In-hospital initiation of lipid-lowering therapy after coronary intervention as a
      predictor of long-term utilization: a propensity analysis.
AB  - BACKGROUND: Despite multiple randomized trials demonstrating their efficacy for
      the secondary prevention of coronary disease, lipid-lowering agents remain
      underused. Few studies have examined the relationship between predischarge
      initiation of lipid-lowering therapy and long-term use. METHODS: Using data from
      patients at 69 centers from the United States and Canada enrolled in the
      Evaluation in PTCA to Improve Long-term Outcome With Abciximab GP IIb/IIIa
      Blockade (EPILOG) trial, we performed a retrospective propensity-analyzed cohort
      study. Patients underwent percutaneous coronary intervention for stable or
      recently unstable coronary disease and were older than 21 years, were not taking
      lipid-lowering therapy at the time of admission, and survived to hospital
      discharge; 175 were discharged taking lipid-lowering therapy and 1951 were not.
      RESULTS: After 6 months, 77% of patients who started taking lipid-lowering agents
      before hospital discharge continued taking therapy, compared with only 25% of
      those discharged without these agents (relative risk, 3.17; 95% confidence
      interval, 2.88-3.41; P<.001). After restricting the analysis to propensity
      matched patients (n = 477) and adjusting for other potential confounders,
      initiation of a lipid-lowering agent during hospitalization was the strongest
      independent predictor of use at 6 months (relative risk, 2.50; 95% confidence
      interval, 2.29-2.65; P<.001). CONCLUSIONS: Inpatient initiation of lipid-lowering
      therapy is a strong and independent positive predictor of subsequent use, with
      patients who start taking lipid-lowering therapy before hospital discharge nearly
      3 times as likely to be taking these agents 6 months later. Inpatient initiation
      of lipid-lowering therapy appears to be an effective strategy for bridging the
      gap between current medical knowledge and practice.

PMID- 14638558
TI  - Conversion from intravenous to oral medications: assessment of a computerized
      intervention for hospitalized patients.
AB  - BACKGROUND: Many hospitalized patients continue to receive intravenous
      medications longer than necessary. Earlier conversion from the intravenous to the
      oral route could increase patient safety and comfort, reduce costs, and
      facilitate earlier discharge from the hospital without compromising clinical
      care. We examined the effect of a computer-based intervention to prompt
      physicians to switch appropriate patients from intravenous to oral medications.
      METHODS: This study was performed at Brigham and Women's Hospital, an academic
      tertiary care hospital at which all medications are ordered online. We targeted 5
      medications with equal oral and intravenous bioavailability: fluconazole,
      levofloxacin, metronidazole, ranitidine, and amiodarone. We used the hospital's
      computerized order entry system to prompt physicians to convert appropriate
      intravenous medications to the oral route. We measured the total use of the
      targeted medications via each route in the 4 months before and after the
      implementation of the intervention. We also measured the rate at which physicians
      responded to the intervention when prompted. RESULTS: The average intravenous
      defined daily dose declined by 11.1% (P =.002) from the preintervention to the
      postintervention period, while the average oral defined daily dose increased by
      3.7% (P =.002). Length of stay, case-mix index, and total drug use at the
      hospital increased during the study period. The average total monthly use of the
      intravenous preparation of all of the targeted medications declined in the 4
      months after the intervention began, compared with the 4 months before. In 35.6%
      of 1045 orders for which a prompt was generated, the physician either made a
      conversion from the intravenous to the oral version or canceled the order
      altogether. CONCLUSIONS: Computer-generated reminders can produce a substantial
      reduction in excessive use of targeted intravenous medications. As online
      prescribing becomes more common, this approach can be used to reduce excess use
      of intravenous medications, with potential benefits in patient comfort, safety,
      and cost.

PMID- 14638559
TI  - Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes
      mellitus: systematic review and meta-analysis.
AB  - BACKGROUND: Metformin therapy for type 2 diabetes mellitus has been shown to
      reduce total mortality rates compared with other antihyperglycemic treatments but
      is thought to increase the risk of lactic acidosis. The true incidence of fatal
      and nonfatal lactic acidosis associated with metformin use is not known. METHODS:
      A comprehensive search was performed to identify all comparative trials or
      observational cohort studies published between January 1, 1959, and March 31,
      2002, that evaluated metformin therapy, alone or in combination with other
      treatments, for at least 1 month. The incidence of fatal and nonfatal lactic
      acidosis was recorded as cases per patient-years for metformin treatment and for
      placebo or other treatments. In a second analysis, lactate levels were measured
      as a net change from baseline or as mean treatment values for metformin and
      comparison groups. RESULTS: Pooled data from 194 studies revealed no cases of
      fatal or nonfatal lactic acidosis in 36 893 patient-years in the metformin group
      or in 30 109 patients-years in the nonmetformin group. Using Poisson statistics
      with 95% confidence intervals, the probable upper limit for the true incidence of
      lactic acidosis in the metformin and nonmetformin groups was 8.1 and 9.9 cases
      per 100 000 patient-years, respectively. There was no difference in lactate
      levels for metformin compared with placebo or other nonbiguanide therapies.
      CONCLUSION: There is no evidence to date that metformin therapy is associated
      with an increased risk of lactic acidosis or with increased levels of lactate
      compared with other antihyperglycemic treatments if the drugs are prescribed
      under study conditions, taking into account contraindications.

PMID- 14638560
TI  - Blood exposures and hepatitis C virus infections among emergency responders.
AB  - BACKGROUND: Blood exposures in the workplace may put first responders, a group
      which includes firefighters, emergency medical technicians, and paramedics, at
      increased risk for hepatitis C virus (HCV) infection. To determine the prevalence
      of antibody to HCV (anti-HCV) and risk factors for infection among first
      responders, we analyzed data from prevalence surveys conducted among first
      responders in Atlanta, Ga, in 1991; Connecticut in 1992; and Philadelphia, Pa, in
      1999. METHODS: Serum or blood samples from participants of the 3 surveys were
      tested for anti-HCV. Prevalence of anti-HCV was compared with that in the general
      US population and among participants by occupational (Atlanta) and
      nonoccupational (Atlanta and Philadelphia) risk factors for infection. RESULTS:
      Prevalence of anti-HCV among the 2946 participants of the 3 surveys ranged from
      1.3% to 3.6% and was no different than among appropriate referent groups in the
      general US population. First responders in Atlanta reported high rates of skin
      exposures to blood (174 per 100 person-years) but few mucosal or needle-stick
      exposures (1 and 0 per 100 person-years, respectively) during the 6 months prior
      to the survey. Hepatitis C virus infection was not associated with a history of
      skin exposures to blood (prevalence ratio [PR], 1.1; 95% confidence interval
      [CI], 0.3-4.2), and HCV prevalence did not increase with longer duration (>10
      years) of employment (PR, 1.1; 95% CI, 0.3-4.3). Nonoccupational risk factors
      associated with HCV infection included history of a sexually transmitted disease
      (PR, 7.4; 95% CI, 1.6-35.3) among Atlanta participants and histories of illegal
      drug use (PR, 4.4; 95% CI, 2.6-7.2) and blood transfusion before 1992 (PR, 1.9;
      95% CI, 1.1-3.3) among Philadelphia participants. CONCLUSIONS: First responders
      are exposed to blood in the workplace, and standard precautions should be
      rigorously implemented. Although risk for HCV infection related to percutaneous
      or mucosal exposures could not be accurately assessed, the low prevalence of HCV
      infection indicates that routine HCV testing of first responders as an
      occupational group is not warranted. Testing should routinely be offered to those
      requiring postexposure management and those with a history of nonoccupational
      risk factors indicating an increased risk for infection.

PMID- 14638561
TI  - Deep vein thrombosis in elderly patients hospitalized in subacute care
      facilities: a multicenter cross-sectional study of risk factors, prophylaxis, and
      prevalence.
AB  - BACKGROUND: The efficacy of venous thromboembolism prophylaxis has not been
      established, to our knowledge, in elderly patients hospitalized in subacute care
      facilities. OBJECTIVES: To describe risk factors and physician practices in the
      prevention of venous thromboembolism and to estimate the prevalence of deep vein
      thrombosis. METHODS: A multicenter cross-sectional study was conducted in the
      subacute care departments of 36 French hospitals. The study population included
      852 inpatients older than 64 years. Systematic ultrasound examination was
      performed by angiologists. RESULTS: Of the 852 inpatients, 178 (20.9%; 95%
      confidence interval [CI], 18.2%-23.8%) had 3 or more risk factors other than age,
      while 144 patients (16.9%; 95% CI, 14.4%-19.6%) had none. The rate of
      prophylactic anticoagulant treatment was 56.1%, ranging from 20.0% to 86.9%,
      depending on the department. In multivariate analysis, prophylaxis use was
      associated with acute immobilization (odds ratio [OR], 4.17; 95% CI, 2.48-7.01),
      chronic immobilization (OR, 3.19; 95% CI, 2.22-4.60), major surgical procedure
      (OR, 6.81; 95% CI, 4.26-10.88), and congestive heart failure (OR, 1.65; 95% CI,
      1.02-2.67). Prophylaxis use was low in patients who had cancer (OR, 0.49; 95% CI,
      0.29-0.84) or myocardial infarction (OR, 0.39; 95% CI, 0.14-1.00). It was not
      significantly associated with paralytic stroke or history of venous
      thromboembolism. Deep vein thrombosis was detected in 135 patients (15.8%; 95%
      CI, 13.4%-18.5%): 50 (5.9%; 95% CI, 4.4%-7.7%) had proximal vein thrombosis and
      85 (10.0%; 95% CI, 8.0%-12.2%) had calf vein thrombosis. CONCLUSIONS: The
      prevalence of deep venous thrombosis is high in these patients, despite wide use
      of prophylaxis. Further prospective studies assessing the clinical benefit of
      extended duration prophylaxis are needed in elderly patients hospitalized in
      subacute care settings.

PMID- 14638562
TI  - Suggested guidelines for evaluation and treatment of glucocorticoid-induced
      osteoporosis for the Department of Veterans Affairs.
AB  - BACKGROUND: Glucocorticoid-induced osteoporosis is an important disorder in the
      predominantly male US veteran population. Department of Veterans Affairs
      facilities vary considerably in evaluation and management of glucocorticoid
      induced osteoporosis. METHODS: We suggest how evaluation and management can take
      place in medical centers with and without bone mineral density measurements by
      dual energy x-ray absorptiometry (DXA). The proposed guidelines can be applied to
      other health care systems. RESULTS: Use of DXA can help determine fracture risk
      for patients taking glucocorticoid therapy and for those starting therapy for at
      least 3 months. Patients with low bone mineral density should be treated with a
      bisphosponate as should all patients about to start prednisone treatment at a
      dose of 7.5 mg/d or more. In facilities without DXA, most patients should be
      treated with bisphosphonates, the cost of which is about $30 to $35 per month. In
      addition, the use of urinary calcium measurements is encouraged to determine
      which patients might benefit from augmented vitamin D and calcium
      supplementation. CONCLUSION: Attention to fracture risk assessment in patients
      undergoing glucocorticoid therapy and timely bisphosphonate treatment should lead
      to fewer fractures.

PMID- 14638563
TI  - Physicians' decisions to override computerized drug alerts in primary care.
AB  - BACKGROUND: Although computerized physician order entry reduces medication errors
      among inpatients, little is known about the use of this system in primary care.
      METHODS: We calculated the override rate among 3481 consecutive alerts generated
      at 5 adult primary care practices that use a common computerized physician order
      entry system for prescription writing. For detailed review, we selected a random
      sample of 67 alerts in which physicians did not prescribe an alerted medication
      and 122 alerts that resulted in a written prescription. We identified factors
      associated with the physicians' decisions to override a medication alert, and
      determined whether an adverse drug event (ADE) occurred. RESULTS: Physicians
      overrode 91.2% of drug allergy and 89.4% of high-severity drug interaction
      alerts. In the multivariable analysis using the medical chart review sample (n =
      189), physicians were less likely to prescribe an alerted medication if the
      prescriber was a house officer (odds ratio [OR], 0.26; 95% confidence interval
      [CI], 0.08-0.84) and if the patient had many drug allergies (OR, 0.70; 95% CI,
      0.53-0.93). They were more likely to override alerts for renewals compared with
      new prescriptions (OR, 17.74; 95% CI, 5.60-56.18). We found no ADEs in cases
      where physicians observed the alert and 3 ADEs among patients with alert
      overrides, a nonsignificant difference (P =.55). Physician reviewers judged that
      36.5% of the alerts were inappropriate. CONCLUSIONS: Few physicians changed their
      prescription in response to a drug allergy or interaction alert, and there were
      few ADEs, suggesting that the threshold for alerting was set too low.
      Computerized physician order entry systems should suppress alerts for renewals of
      medication combinations that patients currently tolerate.

PMID- 14638564
TI  - The long-term effects of a self-management program for inner-city primary care
      patients with acute low back pain.
AB  - BACKGROUND: We evaluated the effect of a self-management program for low-income
      primary care patients with acute low back pain (ALBP) from inner-city
      neighborhood health centers. METHODS: We conducted a randomized controlled trial
      of a self-management program compared with usual care at university-affiliated
      neighborhood health centers and an emergency department of an inner-city public
      teaching hospital. We enrolled 211 patients who visited a physician for ALBP (<90
      days' duration). The self-management program consisted of 3 group sessions and
      telephone follow-up that focused on understanding back pain, increasing physical
      activity, and dealing with fears and frustrations. RESULTS: At baseline, 4
      months, and 12 months, blinded interviewers assessed back pain physical function
      (Roland Disability Questionnaire), health status (Arthritis Impact Measurement
      Scales), self-efficacy, and time spent in physical activity. Compared with
      patients receiving usual care, intervention patients reported significantly
      better scores on the Roland Disability Questionnaire (P =.009), mental
      functioning (P =.009), self-efficacy to manage ALBP (P =.03), time spent in
      physical activity (P =.047), and reduced fears of movement/reinjury (P =.005)
      after 12 months. CONCLUSION: A self-management program can improve and maintain
      functional status, mental functioning, and self-efficacy to manage future
      symptoms for 1 year among primary care patients with ALBP living in the urban,
      inner city.

PMID- 14638566
TI  - Article on walking and diabetes omitted some relevant studies.

PMID- 14638565
TI  - Comparison of the quality of oral anticoagulant therapy through patient self
      management and management by specialized anticoagulation clinics in the
      Netherlands: a randomized clinical trial.
AB  - BACKGROUND: Several studies have demonstrated that patient self-management of
      oral anticoagulant therapy (OAT) can improve treatment quality. However, most of
      these studies were not conducted within a specialized anticoagulation care
      system. The objective of the present study was to determine whether patient self
      management of OAT improves the quality of care delivered by anticoagulation
      clinics. METHODS: In this randomized study by 2 Dutch anticoagulation clinics 341
      patients aged between 18 and 75 years and receiving long-term OAT were divided
      into 4 groups: an existing routine care group of patients untrained in self
      management; a routine care group of trained patients; a group managed weekly at
      an anticoagulation clinic where international normalized ratios were measured by
      trained patients; and weekly patient self-management. A 2-step randomization
      procedure was followed: first, a Zelen-design randomization was performed to
      distribute patients (without informing them) to the existing care group or to
      receive training in self-management; second, trained patients were randomized to
      the 3 other study groups. RESULTS: Only 25.6% of invited patients agreed to
      participate in the training program. Patients who remained in the existing care
      group were within the international normalized ratio target range 63.5% of the
      time. The type of coumarin taken was a major predicting factor of OAT quality. In
      all study groups phenprocoumon outperformed acenocoumarol by 11.6% (95%
      confidence interval [CI], 6.6%-16.5%). Weekly management with phenprocoumon led
      to a 6.5% improvement (95% CI, 0.0%-13.1%) in time in the international
      normalized ratio target range when patients were managed at an anticoagulation
      clinic and to an 8.7% improvement (95% CI, 1.6%-15.9%) when patients were self
      managed. Weekly management with acenocoumarol did not improve the quality of OAT.
      CONCLUSION: With selected patients, the quality of OAT obtained through patient
      self-management is at least as high as that delivered by specialized physicians
      at anticoagulation clinics. Weekly management of OAT with long-acting
      phenprocoumon has to be preferred at anticoagulation clinics or, where possible,
      through patient self-management.

PMID- 14638567
TI  - Quality improvement projects: inaction presents the greatest risk.

PMID- 14638568
TI  - Risk of unexplained acute liver failure in diabetes mellitus.

PMID- 14638569
TI  - Hypertension in acute stroke.

PMID- 14638570
TI  - White coat cover-up.

PMID- 14638571
TI  - Stethoscopes as neckwear.

PMID- 14638572
TI  - The course of bipolar disorder and the nature of agitated depression.

PMID- 14638573
TI  - Effectiveness of disease management programs in depression: a systematic review.
AB  - OBJECTIVE: The authors systematically evaluated the published evidence to assess
      the effectiveness of disease management programs in depression. METHOD: English
      language articles on depression were identified through a MEDLINE search for the
      period from January 1987 to June 2001. Two reviewers evaluated 16,952 published
      titles, identified 24 depression disease management programs that met explicit
      inclusion criteria, and extracted data on study characteristics, interventions
      used, and outcome measures. Pooled effect sizes were calculated by using a random
      effects model. RESULTS: Pooled results for disease management program effects on
      symptoms of depression showed statistically significant improvements (effect
      size=0.33, N=24). Programs also had statistically significant effects on
      patients' satisfaction with treatment (effect size=0.51, N=6), patients'
      compliance with the recommended treatment regimen (effect size=0.36, N=7), and
      adequacy of prescribed treatment (effect size=0.44, N=11). One program with an
      explicit screening component showed significant improvement in the rate of
      detection of depression by primary care physicians (effect size=0.66); two other
      programs lacking a screening component showed small nonsignificant improvements
      in the detection rate (effect size=0.18). Disease management programs increased
      health care utilization (effect size=-0.10, N=8), treatment costs (effect size=
      1.03, N=3), and hospitalization (effect size=-0.20, N=2). CONCLUSIONS: Disease
      management appears to improve the detection and care of patients with depression.
      Further research is needed to assess the cost-effectiveness of disease management
      in depression, and consideration should be given to more widespread
      implementation of these programs.

PMID- 14638574
TI  - Schizophrenia, VIII: pharmacologic models.

PMID- 14638575
TI  - Memories of the Pacific Coast.

PMID- 14638576
TI  - A physician's suicide.

PMID- 14638577
TI  - Taunton State Hospital, Massachusetts.

PMID- 14638578
TI  - The McLean-Harvard First-Episode Mania Study: prediction of recovery and first
      recurrence.
AB  - OBJECTIVE: Since improved prediction of illness course early in bipolar disorder
      is required to guide treatment planning, the authors evaluated recovery, first
      recurrence, and new illness onset following first hospitalization for mania.
      METHOD: Bipolar disorder patients (N=166) were followed 2-4 years after their
      first hospitalization for a manic or mixed episode to assess timing and
      predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM
      IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale
      score </=5 and Hamilton Depression Rating Scale score </=8), and functional
      (regaining of premorbid occupational and residential status). Rates of remission
      (syndromal recovery sustained >/=8 weeks), switching (onset of new dissimilar
      illness before recovery), relapse (new episode of mania within 8 weeks of
      syndromal recovery), and recurrence (new episode postremission) were also
      assessed. RESULTS: By 2 years, most subjects achieved syndromal recovery (98%,
      with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery.
      Factors associated with a shorter time to syndromal recovery for 50% of the
      subjects were female sex, shorter index hospitalization, and lower initial
      depression ratings. Only 43% achieved functional recovery; these subjects were
      more often older and had shorter index hospitalizations. Within 2 years of
      syndromal recovery, 40% experienced a new episode of mania (20%) or depression
      (20%), and 19% switched phases without recovery. Predictors of mania recurrence
      were initial mood-congruent psychosis, lower premorbid occupational status, and
      initial manic presentation. Predictors of depression onset were higher
      occupational status, initial mixed presentation, and any comorbidity.
      Antidepressant treatment was marginally related to longer time to recovery and
      earlier relapse. CONCLUSIONS: Within 2-4 years of first lifetime hospitalization
      for mania, all but 2% of patients experienced syndromal recovery, but 28%
      remained symptomatic, only 43% achieved functional recovery, and 57% switched or
      had new illness episodes. Risks of new manic and depressive episodes were similar
      but were predicted by contrasting factors.

PMID- 14638579
TI  - Clinical characteristics, 4-year course, and DSM-IV classification of patients
      with nonaffective acute remitting psychosis.
AB  - OBJECTIVE: The authors examined the clinical characteristics and 48-month illness
      course of cases of nonaffective acute remitting psychosis and described the
      classification of these cases in the DSM-IV system. METHOD: The data were derived
      from the Suffolk County (N.Y.) Mental Health Project, a study of first-admission
      patients with psychotic disorders admitted to psychiatric facilities between
      September 1989 and December 1995. The authors compared the demographic and
      clinical characteristics, 48-month course, and longitudinal research diagnoses of
      16 patients with nonaffective acute remitting psychosis, defined by onset in 2
      weeks or less and duration of less than 6 months, to those of 26 patients with
      other nonaffective remitting psychoses. RESULTS: Nonaffective acute remitting
      psychosis had a distinctly benign course-46% of the patients remained in full
      remission throughout the 48-month follow-up, compared with 14% of patients with
      other remitting psychoses. Nonaffective acute remitting psychosis was also
      associated with fewer negative symptoms than other remitting psychoses. By 24
      month follow-up, only 6% of the patients with nonaffective acute remitting
      psychosis, compared with 77% of the patients with other remitting psychoses,
      received a research diagnosis of schizophrenia or schizoaffective disorder,
      whereas 44% of patients with nonaffective acute remitting psychosis, compared
      with 12% of patients with other remitting psychoses, were given the residual
      diagnosis of psychotic disorder not otherwise specified. CONCLUSIONS:
      Nonaffective acute remitting psychosis is a highly distinctive yet not adequately
      classified condition. Better delineation of nonaffective acute remitting
      psychosis in current diagnostic systems could lead to better understanding of
      this condition and improve the applicability of diagnostic systems in developing
      countries, where these conditions are more common than in industrialized
      countries.

PMID- 14638580
TI  - Stable prediction of mood and anxiety disorders based on behavioral and emotional
      problems in childhood: a 14-year follow-up during childhood, adolescence, and
      young adulthood.
AB  - OBJECTIVE: The goal of this study was to predict the onset of mood and anxiety
      disorders from parent-reported emotional and behavioral problems in childhood
      across a 14-year period from childhood into young adulthood. METHOD: In 1983,
      parent reports of behavioral and emotional problems were obtained with the Child
      Behavior Checklist for children and adolescents 4-16 years of age from the Dutch
      general population. At follow-up 14 years later, lifetime mood and anxiety
      diagnoses were obtained by a standardized DSM-IV interview for 1,580 subjects.
      Cox proportional hazards models were used to predict the incidence of mood and
      anxiety disorders from childhood problems and demographic covariates. RESULTS:
      Mood disorders were significantly predicted by high scores on the
      anxious/depressed scale and on the internalizing composite (withdrawn, somatic
      complaints, and anxious/depressed). Anxiety disorders were significantly
      predicted by the social problems scale and the externalizing composite
      (delinquent behavior and aggressive behavior). Anxiety disorders predominantly
      started in childhood and early adolescence, whereas the incidence of mood
      disorders increased sharply in adolescence and young adulthood. CONCLUSIONS:
      These results suggest different developmental pathways for mood and anxiety
      disorders. The predictions based on problem behavior remained stable during the
      14-year period across adolescence and young adulthood. The results therefore
      underline the importance of early intervention and prevention of behavioral and
      emotional problems in childhood.

PMID- 14638581
TI  - The impact of medical comorbidity on acute treatment in major depressive
      disorder.
AB  - OBJECTIVE: The authors investigated the impact of medical comorbidity on the
      acute phase of antidepressant treatment in subjects with major depressive
      disorder. METHOD: A total of 384 outpatients meeting DSM-III-R criteria for major
      depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day.
      The authors used the Cumulative Illness Rating Scale to measure the burden of
      medical comorbidity and the 17-item Hamilton Rating Scale for Depression to
      assess changes in depressive symptoms. The outcome measures were response to
      treatment (>/=50% reduction in score) and clinical remission (score </=7 at the
      end of the trial). RESULTS: Compared to responders to fluoxetine, nonresponders
      had significantly higher Cumulative Illness Rating Scale scores and a greater
      number of Cumulative Illness Rating Scale categories were endorsed. Compared to
      subjects who achieved remission with antidepressant treatment, those who did not
      achieve remission had significantly higher Cumulative Illness Rating Scale scores
      and a greater number of Cumulative Illness Rating Scale categories were endorsed
      (i.e., more organs were affected by medical illness). The final Hamilton
      depression scale score was directly correlated with the total Cumulative Illness
      Rating Scale score and the number of Cumulative Illness Rating Scale categories
      endorsed. CONCLUSIONS: The total burden of medical illness and the number of
      organ systems affected by medical illness had a significantly negative predictive
      value for clinical outcome in the acute phase of treatment in major depressive
      disorder.

PMID- 14638582
TI  - Major depression and associated impairment: same or different genetic and
      environmental risk factors?
AB  - OBJECTIVE: Impairment was added as a diagnostic criterion for many psychiatric
      disorders in DSM-IV. Does the addition of impairment influence only prevalence
      rates, or does it also introduce new etiological factors into psychiatric
      diagnoses? METHOD: A lifetime history of major depression and associated
      functional impairment was assessed by personal interview with 3,669 female and
      4,377 male twins from the population-based Virginia Twin Registry. Structural
      equation modeling was used to estimate the correlation between risk factors for
      major depression and associated functional impairment. RESULTS: While the risk
      factors for major depression and associated functional impairment are
      substantially correlated, they are not identical. The most parsimonious model
      suggests that over a quarter of the variance in associated functional impairment
      is due to factors unrelated to risk for major depression. Of the variance unique
      to associated functional impairment, approximately one-third is familial. The
      relationship between associated functional impairment and major depression did
      not differ significantly between men and women. CONCLUSIONS: Risk factors for
      major depression and associated functional impairment are substantially but
      imperfectly correlated. The addition of associated functional impairment as a
      criterion for the diagnosis of major depression not only lowers prevalence
      estimates but also introduces a small set of new etiological factors into the
      diagnosis of major depression.

PMID- 14638583
TI  - Agitated depression in bipolar I disorder: prevalence, phenomenology, and
      outcome.
AB  - OBJECTIVE: The study aimed to explore how prevalent agitated depression is in
      bipolar I disorder, whether it represents a mixed state, and whether it differs
      from nonagitated depression with respect to course and outcome. METHOD: From 313
      bipolar I patients with an index episode of major depression, the authors
      selected those fulfilling Research Diagnostic Criteria for agitated depression.
      These 61 patients were compared to 61 randomly recruited bipolar I patients with
      an index episode of nonagitated depression and 61 randomly recruited bipolar I
      patients with an index episode of mania regarding demographic, historical, and
      clinical features. The two depressive groups were also compared regarding time to
      recovery from the index episode, treatment received for that episode, percentage
      of time spent in an affective episode during a prospective observation period,
      and 5-year outcome. RESULTS: Patients with agitated depression were consistently
      not elated or grandiose, but one-fourth had the cluster of symptoms with racing
      thoughts, pressured speech, and increased motor activity, and one-fourth had the
      paranoia-aggression-irritability cluster. Compared to patients with nonagitated
      depression, they had a longer time to 50% probability of recovery from the index
      episode, were more likely to receive standard antipsychotic drugs during that
      episode, and spent more time in an affective episode during the observation
      period. CONCLUSIONS: The occurrence of agitated depression in bipolar I disorder
      is not rare and has significant prognostic and therapeutic implications. Whether
      the co-occurrence of a major depressive syndrome with one or two of these
      symptomatic clusters makes up a "mixed state" remains unclear.

PMID- 14638584
TI  - Childhood and adolescent predictors of major depression in the transition to
      adulthood.
AB  - OBJECTIVE: The identification of predictors of major depression in the transition
      to adulthood has direct application to prevention and intervention efforts
      designed to forestall depression in this high-risk period. The current study
      identified childhood and adolescent familial and behavioral-emotional factors
      predicting depression during this critical developmental stage. METHOD: The 354
      participants were part of a single-age cohort from a predominately Caucasian
      working-class community whose psychosocial development has been traced
      prospectively since age 5. In these analyses, data collected during childhood and
      adolescence were related to diagnoses of major depression at ages 18-26. RESULTS:
      During the transition to adulthood, 82 participants (23.2%) experienced major
      depression. Bivariate indicators of later depression included a family history of
      depression or substance use disorders, family composition, and childhood family
      environments perceived as violent and lacking cohesiveness. Also significant were
      self- and mother-reported internalizing behaviors, as well as self-rated anxiety
      and depressive symptoms. Multivariable analyses showed family violence, family
      composition, internalizing problems during adolescence, and low family cohesion
      to be the most salient factors. CONCLUSIONS: These results highlight familial and
      behavioral-emotional predictors of depression that can serve as foci for
      identifying youth in need of intervention.

PMID- 14638585
TI  - Anomalous somatosensory cortical localization in schizophrenia.
AB  - OBJECTIVE: Schizophrenia has been reported to be associated with altered
      localization of regions responding to sound in the auditory cortex, suggesting
      possible cortical reorganization accompanying the disorder, but it is not clear
      whether such disturbances are present in any primary sensory cortex other than
      the auditory. This study examines magnetoencephalographic localization of field
      sources evoked by tactile stimulation generated in area 3b of the primary
      somatosensory cortex in patients with schizophrenia compared with normal
      subjects. METHOD: A total of 29 subjects participated; 14 were patients with
      schizophrenia, and 15 were normal comparison subjects. Equivalent current dipole
      generators in both hemispheres were used to model the sources of the 50-msec
      latency somatosensory evoked field (M50) components produced by contralateral
      tactile mechanoreceptor stimulation of the tip of the index finger. RESULTS:
      Compared with normal subjects, patients with schizophrenia demonstrated reversed
      asymmetry (left anterior to right) and relatively anterior and inferior
      displacement of the M50 equivalent current dipole location in the left
      hemisphere. CONCLUSIONS: Cerebral lateralization and localization of the M50
      distinguished patients with schizophrenia from normal subjects. These findings
      suggest the possibility of anatomical displacement and/or disturbed organization
      of the primary sensory cortex in schizophrenia.

PMID- 14638587
TI  - Increases in regional subarachnoid CSF without apparent cortical gray matter
      deficits in schizophrenia: modulating effects of sex and age.
AB  - OBJECTIVE: The authors investigated the modulating effects of biological sex and
      age on regional decreases in cortical gray matter and increases in subarachnoid
      CSF in 25 patients with chronic schizophrenia and 28 group-matched healthy
      comparison subjects. METHOD: Computational cortical pattern-matching methods were
      employed to measure the local proportions of gray matter and subarachnoid CSF at
      thousands of homologous cortical surface locations in each subject using high
      resolution magnetic resonance images. Principal-component analysis reduced tissue
      proportion values obtained at each cortical surface point into component scores
      for each subject. Principal-component analysis scores were used as dependent
      variables in statistical analyses that included diagnosis, age, and sex as
      predictor variables. To reveal more regional changes in tissue proportions,
      statistical differences in gray matter and CSF were compared at each cortical
      surface location and mapped in three dimensions. RESULTS: Principal-component
      analyses revealed main effects of diagnosis, sex, and age for the CSF increases
      seen in the schizophrenia patients, in male subjects, and in association with
      age. Significant diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-sex-by-age
      interactions were also observed, revealing CSF increases in male patients at
      younger ages. Statistical maps showed regional increases in subarachnoid CSF in
      association with the above effects. For cortical gray matter measurements, only
      main effects of age were observed. CONCLUSIONS: Regionally specific increases in
      sulcal and subarachnoid CSF occur during adulthood and appear prematurely in male
      schizophrenia patients. Cortical gray matter reductions show aging effects but
      are below the threshold of significance in schizophrenia.

PMID- 14638586
TI  - MRI assessment of gray and white matter distribution in Brodmann's areas of the
      cortex in patients with schizophrenia with good and poor outcomes.
AB  - OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to compare
      cortical gray and white matter and CSF volumes in schizophrenia patients with
      poor outcomes, schizophrenia patients with good outcomes, and healthy comparison
      subjects. METHOD: T(1)-weighted, 1.2-mm-thick MR images were acquired for 37
      patients with schizophrenia and 37 healthy, age- and sex-matched comparison
      subjects. The patients were assigned to subgroups with poor outcomes (N=13) and
      good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome
      patients were those who were continuously hospitalized or completely dependent on
      others for basic needs, were unemployed, and had severe negative symptoms and
      severe formal thought disorder. The MR images were reoriented to standard
      position parallel to the anterior commissure-posterior commissure line and
      segmented into CSF, gray matter, and white matter tissue types. The tissue types
      were assigned to Brodmann's areas by using the Perry postmortem histological
      atlas, and tissue-type volumes in the three subject groups were compared.
      RESULTS: Compared to the healthy subjects, the overall patient group had a
      significantly smaller mean cortical gray matter volume and significantly larger
      mean CSF volume, especially in the frontal lobe and left temporal lobe. The
      smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes
      and for volumes with adjustment for whole brain volumes. Compared to patients
      with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had
      significantly smaller gray matter volumes in the temporal and occipital lobes,
      but no difference between groups was found for total frontal lobe volume. Only
      21% of the healthy subjects had volumes 0.5 standard deviations below the mean
      for healthy subjects in any area of the frontal or temporal lobes, compared with
      62% of poor-outcome patients. CONCLUSIONS: Poor outcome in patients with
      schizophrenia may be associated with a more posterior distribution
      (posteriorization) of gray matter deficits across widely distributed cortical
      regions.

PMID- 14638588
TI  - Progressive brain volume loss during adolescence in childhood-onset
      schizophrenia.
AB  - OBJECTIVE: Previous reports have documented a striking progressive reduction in
      cortical gray matter volume during adolescence in patients with childhood-onset
      schizophrenia. This study examined the rate of loss in cortical gray matter
      volume in relation to age and clinical status in adolescent patients over a
      follow-up period of 2-6 years. METHOD: A total of 131 brain magnetic resonance
      imaging scans were acquired for 60 subjects with childhood-onset schizophrenia
      (mean age=14.5 years, SD=2.5), and 140 scans were acquired for 64 matched healthy
      comparison subjects. One or more follow-up scans were acquired at approximately 2
      year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy
      subjects. Developmental trajectories for total and regional brain volumes were
      examined in relation to age by using polynomial growth models and data from all
      available scans. The rate of gray matter reduction in patients with childhood
      onset schizophrenia was examined in relation to developmental and clinical
      measures by using stepwise regression. RESULTS: Rates of brain volume reduction
      were significantly higher for patients with childhood-onset schizophrenia than
      for healthy comparison subjects. In childhood-onset schizophrenia, the rate of
      gray matter reduction was related to premorbid impairment and baseline severity
      of clinical symptoms but not to gender, ethnicity, or age at onset of the
      disorder. Unexpectedly, greater clinical improvement was significantly related to
      a higher rate of gray matter reduction. Longitudinal trajectories suggested that
      the rate of cortical loss plateaus during adolescence. CONCLUSIONS: Striking loss
      of cerebral gray matter is seen through adolescence in patients with childhood
      onset schizophrenia. The rate of reduction was related to premorbid impairment
      and baseline symptom severity, but it may also be in part a plastic response to
      illness.

PMID- 14638589
TI  - Smaller anterior hippocampal formation volume in antipsychotic-naive patients
      with first-episode schizophrenia.
AB  - OBJECTIVE: The authors investigated volumetric alterations of the anterior
      hippocampal formation in patients experiencing a first episode of schizophrenia
      relative to healthy comparison subjects. METHOD: From contiguous 1.5-mm coronal
      magnetic resonance images, the hippocampal formation was divided into posterior
      and anterior segments, and the anterior hippocampal formation was separated from
      the amygdala. Volumes of the posterior and anterior hippocampal formation and
      amygdala were computed in 46 (31 male and 15 female) patients experiencing a
      first episode of schizophrenia and in 34 (21 male and 13 female) healthy
      comparison subjects. Twenty-four patients were antipsychotic naive at the time of
      the scan. RESULTS: Patients had significantly reduced total (right plus left)
      anterior hippocampal formation volume relative to healthy comparison subjects but
      did not differ in volumes of either the posterior hippocampal formation or
      amygdala. Similar findings were obtained when analyses were restricted to the
      antipsychotic-naive subgroup of patients. CONCLUSIONS: These findings suggest
      that volumetric abnormalities of the hippocampus-amygdala complex may be specific
      to the anterior hippocampal formation in patients experiencing a first episode of
      schizophrenia and are consistent with hypotheses regarding abnormal frontolimbic
      connectivity playing a role in the pathophysiology of the disorder.

PMID- 14638590
TI  - An MRI study of superior temporal gyrus volume in women with schizotypal
      personality disorder.
AB  - OBJECTIVE: An abnormal superior temporal gyrus has figured prominently in
      schizophrenia research, and left superior temporal gyrus volume has been shown to
      be smaller in male subjects with schizotypal personality disorder. This is the
      first structural magnetic resonance imaging study to examine a group of female
      subjects with schizotypal personality disorder. METHOD: The superior temporal
      gyrus was drawn on coronal images acquired from female subjects recruited from
      the community (schizotypal personality disorder group: N=21, comparison group:
      N=29). RESULTS: There were no gray matter volume differences in the left or right
      superior temporal gyrus between the subjects with schizotypal personality
      disorder and the comparison subjects. Within the schizotypal personality disorder
      group, however, there was an interaction between hemisphere and family history of
      mental illness. Moreover, subjects with schizotypal personality disorder did
      demonstrate formal thought disorder and a negative correlation between left
      superior temporal gyrus volume and odd speech. CONCLUSIONS: This study of female
      subjects with schizotypal personality disorder showed no superior temporal gyrus
      volume differences, but preliminary findings indicate that among female subjects
      with schizotypal personality disorder, there is a left-right difference in those
      who have a family history of mental illness relative to those who do not. These
      data also suggest an association between abnormal speech and left superior
      temporal gyrus volume, a finding similar to that found in schizophrenia. Results
      from this study thus clearly reinforce the importance of studying female subjects
      separately.

PMID- 14638591
TI  - Long-term course of schizophrenic illness: Bleuler's study reconsidered.
AB  - OBJECTIVE: The influential 1972 study by Manfred Bleuler on the long-term course
      of schizophrenic illness has been reconsidered. The authors tested the diagnosis
      of schizophrenia in all patients and investigated how the distribution of the
      types of illness course and outcome would change after exclusion of patients
      whose diagnosis of schizophrenia could not be confirmed by modern diagnostic
      standards. METHOD: Clinical charts and Bleuler's research notes on the original
      sample were assessed, and all patients were rediagnosed with the help of DSM-IV,
      DSM-III-R, ICD-10, the Research Diagnostic Criteria (RDC), Schneider's criteria,
      and an operationalized version of the criteria of Eugen Bleuler. RESULTS: The
      diagnosis of schizophrenia was not confirmed in about 30% of the sample; the
      majority of these patients were rediagnosed with schizoaffective disorder. High
      diagnostic agreement was found between DSM-IV, DSM-III-R, ICD-10, and RDC; there
      was much less agreement with Bleuler's and Schneider's criteria. After exclusion
      of patients whose schizophrenia diagnosis was not confirmed, the proportion of
      patients with undulating course and recovery slightly decreased, and the
      proportion of patients with severe end state slightly increased. Nevertheless,
      the distribution of the types of long-term course did not significantly change,
      and even among patients with strictly defined schizophrenia, half had an
      undulating course with remissions and 12%-15% recovered. CONCLUSIONS:
      Schizophrenic illness remains heterogeneous with regard to illness course and
      outcome even when narrowly diagnosed with the help of modern operationalized
      diagnostic criteria. Contemporary differentiation between schizophrenic and
      schizoaffective disorders is prognostically valid.

PMID- 14638592
TI  - Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or
      down.
AB  - OBJECTIVE: Numerous neuroimaging studies have examined the function of the
      dorsolateral prefrontal cortex in schizophrenia; although abnormalities usually
      are identified, it is unclear why some studies find too little activation and
      others too much. The authors' goal was to explore this phenomenon. METHOD: They
      used the N-back working memory task and functional magnetic resonance imaging at
      3 T to examine a group of 14 patients with schizophrenia and a matched comparison
      group of 14 healthy subjects. RESULTS: Patients' performance was significantly
      worse on the two-back working memory task than that of healthy subjects. However,
      there were areas within the dorsolateral prefrontal cortex of the patients that
      were more active and areas that were less active than those of the healthy
      subjects. When the groups were subdivided on the basis of performance on the
      working memory task into healthy subjects and patients with high or low
      performance, locales of greater prefrontal activation and locales of less
      activation were found in the high-performing patients but only locales of
      underactivation were found in the low-performing patients. CONCLUSIONS: These
      findings suggest that patients with schizophrenia whose performance on the N-back
      working memory task is similar to that of healthy comparison subjects use greater
      prefrontal resources but achieve lower accuracy (i.e., inefficiency) and that
      other patients with schizophrenia fail to sustain the prefrontal network that
      processes the information, achieving even lower accuracy as a result. These
      findings add to other evidence that abnormalities of prefrontal cortical function
      in schizophrenia are not reducible to simply too much or too little activity but,
      rather, reflect a compromised neural strategy for handling information mediated
      by the dorsolateral prefrontal cortex.

PMID- 14638593
TI  - Investigating the association between cigarette smoking and schizophrenia in a
      cohort study.
AB  - OBJECTIVE: Many case-control and cross-sectional studies have observed an
      association with cigarette smoking after the onset of schizophrenia, and there is
      evidence to suggest that smoking may improve symptoms in people with this
      disorder. Here, the authors investigated whether cigarette smoking alters the
      risk of subsequently developing schizophrenia. No longitudinal studies have
      previously examined this relationship. METHOD: A cohort of 50,087 Swedish
      conscripts (98% were ages 18-20) was followed up by record linkage to the
      National Register of Inpatient Care from 1970 to 1996 to determine hospital
      admission for schizophrenia. Cox regression was used to obtain hazard ratios and
      95% confidence intervals (CIs) for schizophrenia, according to smoking status.
      RESULTS: Smoking cigarettes at ages 18-20 was associated with a lower rate of
      developing schizophrenia after adjustment for confounders. There was a linear
      relationship between the number of cigarettes smoked and a lower risk of
      schizophrenia (adjusted hazard ratio for linear trend across smoking categories,
      0.8 [95% CI=0.7-0.9]), with an adjusted hazard ratio for heavy smokers of 0.5
      (95% CI=0.3-0.9) compared to that of nonsmokers. This association persisted when
      analysis was restricted to subjects diagnosed after the first 5 years following
      conscription to reduce possible prodromal effects of schizophrenia on smoking.
      CONCLUSIONS: Cigarette smoking may be an independent protective factor for
      developing schizophrenia. These results are consistent with animal models showing
      both neuroprotective effects of nicotine and differential release of prefrontal
      dopamine in response to nicotine. The harmful effects of cigarette smoking vastly
      outweigh any possible benefits, but nevertheless, further investigation may lead
      to important insights regarding the etiology of schizophrenia at a molecular
      level.

PMID- 14638594
TI  - Cross-national comparisons of seafood consumption and rates of bipolar disorders.
AB  - OBJECTIVE: The authors sought to determine if greater seafood consumption, a
      measure of omega-3 fatty acid intake, is associated with lower prevalence rates
      of bipolar disorder in community samples. METHOD: Lifetime prevalence rates in
      various countries for bipolar I disorder, bipolar II disorder, bipolar spectrum
      disorder, and schizophrenia were identified from population-based epidemiological
      studies that used similar methods. These epidemiological studies used structured
      diagnostic interviews with similar diagnostic criteria and were population based
      with large sample sizes. Simple linear and nonlinear regression analyses were
      used to compare these prevalence data to differences in apparent seafood
      consumption, an economic measure of disappearance of seafood from the economy.
      RESULTS: Simple exponential decay regressions showed that greater seafood
      consumption predicted lower lifetime prevalence rates of bipolar I disorder,
      bipolar II disorder, and bipolar spectrum disorder. Bipolar II disorder and
      bipolar spectrum disorder had an apparent vulnerability threshold below 50 lb of
      seafood/person/year. The absence of a correlation between lifetime prevalence
      rates of schizophrenia and seafood consumption suggests a specificity to
      affective disorders. CONCLUSIONS: These data describe a robust correlational
      relationship between greater seafood consumption and lower prevalence rates of
      bipolar disorders. These data provide a cross-national context for understanding
      ongoing clinical intervention trials of omega-3 fatty acids in bipolar disorders.

PMID- 14638595
TI  - To whom do psychiatrists offer smoking-cessation counseling?
AB  - OBJECTIVE: Individuals with mental illness have high rates of tobacco dependence;
      however, little is known about what influences a psychiatrist's decision to offer
      smoking-cessation counseling to smoking patients. METHOD: Using the National
      Ambulatory Medical Care Survey, the authors identified 1,610 psychiatric office
      visits for patients who smoke. They investigated the relationship between patient
      and visit characteristics and smoking-cessation counseling with logistic
      regression. RESULTS: Psychiatrists offered cessation counseling at 12.4% of the
      visits for smoking patients. The adjusted probability of receiving smoking
      cessation counseling was significantly higher for those older than 50; for those
      with a medical diagnosis of obesity, hypertension, or diabetes mellitus; for
      those in a rural location; and for those having an initial visit. Those with
      bipolar affective disorder were more likely to receive smoking-cessation
      counseling than those with depression. CONCLUSIONS: Psychiatrists may be missing
      opportunities to offer smoking-cessation counseling to patients who smoke.

PMID- 14638596
TI  - Glutamate and glutamine in the anterior cingulate and thalamus of medicated
      patients with chronic schizophrenia and healthy comparison subjects measured with
      4.0-T proton MRS.
AB  - OBJECTIVE: This in vivo (1)H magnetic resonance spectroscopy study examined
      levels of glutamate, glutamine, and N-acetylaspartate in medicated patients with
      chronic schizophrenia. METHOD: Localized in vivo (1)H spectra were acquired at
      4.0 T from the left anterior cingulate and thalamus of 21 patients with
      schizophrenia and 21 comparable healthy volunteers. RESULTS: Significantly lower
      levels of glutamine and glutamate were found in the left anterior cingulate
      cortex of patients with schizophrenia than in the healthy volunteers. For the
      schizophrenia patients, the glutamine level in the left thalamus was found to be
      higher than normal, and there was a significant negative correlation between N
      acetylaspartate level and duration of positive symptoms. CONCLUSIONS: Since
      previous studies have found higher than normal levels of glutamine in the left
      anterior cingulate of never-treated patients, decreased levels of these
      metabolites in chronic patients could be related to neurodegeneration or the
      effects of chronic medication.

PMID- 14638597
TI  - Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals
      with schizophrenia.
AB  - OBJECTIVE: The study was an investigation of the effect of the antiviral
      medication valacyclovir on the symptoms of outpatients with persistent
      schizophrenia. METHOD: Oral valacyclovir, 1 g twice daily, was administered to 65
      outpatients over 16 weeks along with their usual psychiatric medications. Changes
      in psychiatric symptoms were measured with the Positive and Negative Syndrome
      Scale and were tested for correlations with antibodies to potentially neurotropic
      human herpesviruses, as measured by immunoassay before the start of the therapy.
      RESULTS: There was a significant improvement in the psychiatric symptoms of
      individuals who were seropositive for cytomegalovirus. Improvement was not
      associated with antibodies to other herpesviruses or to a range of demographic
      and clinical variables. CONCLUSIONS: The replication of cytomegalovirus may
      contribute to the symptoms of schizophrenia in some individuals.

PMID- 14638598
TI  - Normal p50 gating in unmedicated schizophrenia outpatients.
AB  - OBJECTIVE: The hypothesis of a sensory gating defect in schizophrenia has been
      supported by studies demonstrating deficient auditory P50 gating in patients. P50
      gating is the relative attenuation of P50 amplitude in the auditory evoked
      potential following the second auditory stimulus of a stimulus pair. METHOD:
      Auditory evoked potentials of 12 unmedicated male patients with schizophrenia and
      24 healthy men were recorded during three runs of 40 click pairs. Three
      alternative waveform-processing strategies were used to analyze the data.
      RESULTS: Regardless of strategy used, the differences between subject groups
      regarding P50 amplitude and gating were nonsignificant. CONCLUSIONS: The P50
      gating in the patient group was normal. The results do not support the concept of
      the P50 gating defect as a general trait marker of schizophrenia.

PMID- 14638599
TI  - EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective
      disorder, and schizotypal personality disorder.
AB  - OBJECTIVE: The authors tested whether neural synchronization deficits were
      present in subjects with schizophrenia and schizotypal personality disorder.
      METHOD: Amplitude-modulated tones were used to evaluate auditory steady-state
      evoked potential entrainment in a combined group of 21 subjects with
      schizophrenia or schizoaffective disorder, 11 subjects with schizotypal
      personality disorder, and 22 nonpsychiatric comparison subjects. RESULTS: The
      schizophrenia or schizoaffective disorder group exhibited decreased power
      compared to the schizotypal personality disorder and nonpsychiatric comparison
      groups. There were no differences between groups in N100 amplitude. CONCLUSIONS:
      Subjects with schizophrenia but not subjects with schizotypal personality
      disorder have deficits in steady-state responses to periodic stimuli, despite an
      intact response to sensory-evoked potentials (N100). These deficits reflect
      aberrant neural synchronization or resolution and may contribute to disturbed
      perceptual and cognitive integration in schizophrenia.

PMID- 14638600
TI  - Deaths from diabetic ketoacidosis after long-term clozapine treatment.

PMID- 14638601
TI  - Fatal olanzapine-induced ketoacidosis.

PMID- 14638602
TI  - Lethal gastroenteritis associated with clozapine and loperamide.

PMID- 14638603
TI  - Antipsychotic-induced paroxysmal perceptual alteration.

PMID- 14638604
TI  - Symptomatic bradyarrhythmia secondary to risperidone.

PMID- 14638618
TI  - Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced
      obesity.
AB  - The objective of this study was to determine the effect of pioglitazone on blood
      pressure (BP) and oxidative balance in obese, hypertensive, Sprague-Dawley rats
      and to identify some of the molecular mechanisms involved. After 12 weeks of a
      moderately high-fat diet, rats diverged into obesity-prone (OP) and obesity
      resistant (OR) groups (n=6 per group). At the end of the diet, peroxisome
      proliferator activated receptor-gamma (PPARgamma) mRNA expression and activity in
      the renal cortex and medulla of OP rats were significantly lower compared with
      that in OR rats. Pioglitazone treatment increased PPARgamma expression and
      activity in OP rats, suggesting a possible direct ligand-related effect of
      pioglitazone. As opposed to the untreated OP group, which showed moderate
      hypertension (systolic BP=159+/-5.3 mm Hg) after 12 weeks, pioglitazone-treated
      rats were normotensive (systolic BP=123.9+/-2.7 mm Hg). Insulin production was
      reduced by 2-fold in the OP group treated with pioglitazone. Urinary isoprostanes
      and renal lipid peroxides were also reduced in OP rats treated with pioglitazone
      compared with untreated counterparts. Also, expression of p47phox and gp91phox,
      both increased in OP versus OR rats, was reduced in the former by pioglitazone
      treatment. In addition, pioglitazone treatment increased nitrate/nitrite
      excretion and expression of renal endothelial and neuronal nitric oxide synthase.
      Collectively, the results show that pioglitazone treatment prevented hypertension
      and renal oxidative stress both by reducing free-radical production and by
      increasing nitric oxide production/availability.

PMID- 14638619
TI  - Hypertension treatment and control in five European countries, Canada, and the
      United States.
AB  - Levels of hypertension treatment and control have been noted to vary between
      Europe and North America, although direct comparisons with similar methods have
      not been undertaken. In this study, we sought to estimate the relative impact of
      hypertension treatment strategies in Germany, Sweden, England, Spain, Italy,
      Canada, and the United States by using sample surveys conducted in the 1990s.
      Hypertension was defined as a blood pressure of 160/95 mm Hg or 140/90 mm Hg,
      plus persons taking antihypertensive medication. "Controlled hypertension" was
      defined as a blood pressure less than threshold among persons taking
      antihypertensive medications. Among persons 35 to 64 years, 66% of hypertensives
      in the United States had their blood pressure controlled at 160/95 mm Hg,
      compared with 49% in Canada and 23% to 38% in Europe. Similar discrepancies were
      apparent at the 140/90 mm Hg threshold, at which 29% of hypertensives in the
      United States, 17% in Canada, and </=10% in European countries had their blood
      pressure controlled. At the 140/90 mm Hg cutpoint, two thirds to three quarters
      of the hypertensives in Canada and Europe were untreated compared with slightly
      less than half in the United States. Although guidelines vary among countries,
      resulting in different case definitions, this does not account entirely for the
      varying success of different national control efforts. Low treatment and control
      rates in Europe, combined with a higher prevalence of hypertension, could
      contribute to a higher burden of cardiovascular disease risk attributable to
      elevated blood pressure compared with that in North America.

PMID- 14638620
TI  - Low [Mg2+]e enhances arterial spontaneous tone via phosphatidylinositol 3-kinase
      in DOCA-salt hypertension.
AB  - Phosphatidylinositol 3-kinase (PI3K) has been implicated in low extracellular
      Mg2+ concentration ( [Mg2+]e)-induced aortic contraction, and Mg2+ deficiency has
      been associated with hypertension. Moreover, arterial PI3K activity is increased
      in hypertensive deoxycorticosterone (DOCA)-salt rats. We hypothesized that low
      [Mg2+]e activates PI3K, eliciting enhanced vascular contraction, PI3K activity,
      and norepinephrine (NE)-induced contraction. Spontaneous tone was monitored in
      endothelium-denuded aortic strips from sham and DOCA-salt rats exposed to low
      Mg2+ (0.15 mmol/L), high Mg2+ (4.8 mmol/L), or normal (1.17 mmol/L) physiologic
      salt solution (PSS) in isolated tissue baths. LY294002 (20 micromol/L), a PI3K
      inhibitor, or vehicle was added (30 minutes), followed by NE (10(-9) to 3 x10(-5)
      mol/L). Low [Mg2+]e significantly enhanced tone in aortas from DOCA-salt and sham
      rats compared with normal PSS (DOCA-salt low [Mg2+]e, +51.5 +7.0 vs DOCA-salt
      normal PSS, +7.1 +1.4 % of initial phenylephrine [PE] contraction). LY294002 and
      incubation with high Mg2+ PSS decreased tone in aortas from DOCA-salt rats (low
      [Mg2+]e LY294002, --87.5 +8.8; normal PSS LY294002, -81.7 +13.7; and high
      [Mg2+]e, -31.2 +10.8 % of initial PE contraction). Low [Mg2+]e leftward-shifted
      NE-induced aortic contractions in sham and thus matched the shift observed with
      DOCA (-log EC50 mol/L: sham PSS, -7.7 +0.1; DOCA-salt PSS, -8.2 +0.1; sham low
      [Mg2+]e, -8.2 +0.1; and DOCA-salt low [Mg2+]e, -8.1 +0.1). Moreover, this shift
      was inhibited by LY294002. In conclusion, low [Mg2+]e might activate PI3K,
      leading to enhanced tone and agonist-induced contraction observed in aortas from
      DOCA-salt hypertensive rats.

PMID- 14638621
TI  - Hydrochlorothiazide versus chlorthalidone: evidence supporting their
      interchangeability.
AB  - Thiazide diuretics are one of the preferred pharmacologic treatments for
      hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most
      commonly used diuretics in major clinical trials. Treatment guidelines and
      compendia often consider these 2 drugs interchangeable agents within the class of
      thiazide or thiazide-like diuretics. Many sources list them as equipotent.
      Despite these beliefs, there is some suggestion that cardiovascular outcomes are
      not necessarily the same with these 2 drugs. We conducted a literature search
      from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and
      blood pressure-lowering effects of these 2 agents. There are significant
      pharmacokinetic and pharmacodynamic differences between these diuretics.
      Chlorthalidone is approximately 1.5 to 2.0 times as potent as
      hydrochlorothiazide, and the former has a much longer duration of action. Whether
      these pharmacokinetic and pharmacodynamic features cause differences in outcomes
      is not known.

PMID- 14638622
TI  - Implication of an AGT haplotype in a multigene association study with pregnancy
      hypertension.
AB  - Several association studies of candidate genes for preeclampsia and essential
      hypertension have led to discordant results, partly because of small sample
      sizes. Using a large population-based sample of pregnant women, we conducted an
      association study of 10 polymorphisms in 9 genes and aimed (1) to validate 10
      published associations with preeclampsia or essential hypertension, (2) to
      investigate candidate polymorphisms previously associated with preeclampsia for
      association with essential hypertension and similarly with polymorphisms
      previously associated with essential hypertension. From a prospective sample of
      3391 nulliparous French Canadian pregnant women, we identified 180 cases of
      preeclampsia, 203 cases of essential hypertension that were matched with
      normotensive control subjects (n=310 and 357, respectively). Polymorphisms were
      genotyped by allele-specific PCR. Among our candidate polymorphisms, the Met
      allele of Thr174Met of AGT was associated with preeclampsia (P=0.0033). Haplotype
      analysis revealed that the A-Met-Thr (G1035A-Thr174Met-Met235Thr) haplotype was
      associated with a 2.1-fold increased risk of preeclampsia (95% CI, 1.4 to 3.4;
      P=0.0008). In conclusion, we observed a strong association between a specific AGT
      haplotype and preeclampsia in our population, without replicating previous
      published associations with either preeclampsia or essential hypertension. Our
      data support a role for AGT in genetic susceptibility to preeclampsia.

PMID- 14638623
TI  - Different growth factor activation in the right and left ventricles in
      experimental volume overload.
AB  - Mechanical factors play a key role in activation of cardiac growth factor
      response in hemodynamic overload, and both cooperate in myocardial remodeling.
      The present study was performed to investigate whether a different growth factor
      response is activated in the right and left ventricles in aortocaval fistula and
      its effects on regional myocardial adaptation. Relations between regional growth
      factor expression (angiotensin II, insulin-like growth factor-I, and endothelin
      1), myocyte shape changes, and collagen deposition were investigated at mRNA and
      peptide levels in adult pigs after the creation of an aortocaval fistula distal
      to the renal arteries (n=15) and in sham-operated animals (n=15). The role of
      angiotensin II was investigated by the administration of angiotensin-converting
      enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle,
      pure volume overload was accompanied by persistent increase of insulin-like
      growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3
      months, P<0.05), and significant increase of myocyte length (+29% at 3 months,
      P<0.05). Conversely, the mixed pressure-volume overload faced by the right
      ventricle resulted in significant regional overexpression of all growth factors
      investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1),
      with corresponding increase of myocyte diameter and length and collagen
      deposition (+117% at 3 months). Collagen accumulation in the right ventricle as
      well as the increase in right ventricular end-diastolic pressure at the 3-month
      observation were inhibited by angiotensin II antagonism. The left and right
      ventricles respond differently to aortocaval fistula, and local growth factor
      expression is closely related to the regional myocardial adaptation.

PMID- 14638624
TI  - ROS during the acute phase of Ang II hypertension participates in cardiovascular
      MAPK activation but not vasoconstriction.
AB  - The relations among hypertensive response, oxidative stress, and mitogen
      activated protein kinase (MAPK) in cardiovascular tissues have not been fully
      established. We investigated the involvement of reactive oxygen species on
      changes in the hemodynamics and cardiovascular MAPKs activities induced by
      acutely administered angiotensin II (Ang II) in conscious normotensive rats with
      or without treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6
      tetramethyl piperidinoxyl (tempol). Intravenous infusion of a pressor dose of Ang
      II rapidly increased mean arterial blood pressure (MBP) by 53+/-5 mm Hg. After a
      30-minute treatment with Ang II, phosphorylated MAPKs (ERK1/2, JNK, p38) as well
      as thiobarbital reactive substances (T-BARS) were increased in the aorta and
      cardiac left ventricle. Tempol had no significant effect on the elevation of MBP
      elicited by Ang II; however, it dose-dependently suppressed the augmented
      phosphorylation of cardiovascular MAPKs and increased T-BARS levels in plasma and
      tissues induced by Ang II. An acutely administered pressor dose of phenylephrine,
      an alpha-adrenoceptor agonist, also showed tempol-sensitive cardiovascular MAPK
      activation and tempol-insensitive blood pressure elevation. These in vivo data
      indicate that acute administration of Ang II or phenylephrine provoked an
      increase in oxidative stress in the cardiovascular tissues leading to the
      activation of MAPKs, whether it was mediated by pressure overload or the direct
      action of these vasoconstrictors, and that oxidative stress might not have a
      major contribution to the acute hypertensive responses elicited by the
      vasoconstrictors.

PMID- 14638626
TI  - Role of membrane potential and expression of endothelial factors in restenosis
      after angioplasty in SHR.
AB  - We examined the roles played by impaired K+ channels, diminished nitric oxide
      (NO) production, endothelin release, and smooth muscle membrane potential in the
      increased restenosis observed in spontaneously hypertensive rat (SHR) carotid
      arteries after angioplasty. The SHR carotid was found to be less polarized than
      that of normotensive Wistar rats (NWR), and it was further depolarized by the
      alpha2 agonist UK 14,304. This response was blocked by iberiotoxin, indicating
      that calcium-dependent K+ channels operate normally in the SHR carotid.
      Acetylcholine caused a hyperpolarization that was significantly smaller in SHR
      than in NWR carotids, indicating a deficient release of NO in the SHR. After
      angioplasty, SHR and NWR vessels were depolarized, returning to baseline after 10
      days. In the SHR but not in the NWR the contralateral carotid was also
      depolarized, and this was prevented by the endothelin A/B receptor antagonist
      bosentan. After angioplasty, endothelin-1 plasma levels increased in both SHR and
      NWR, but the increase was significantly more prolonged in SHR. We found that the
      more pronounced restenosis observed in the SHR carotid after angioplasty is not
      due to impairment of calcium-dependent K+ channels but is related to the
      relatively depolarized vascular smooth muscles, involving endothelin release
      caused by reduced NO levels in that strain.

PMID- 14638627
TI  - Aldosterone antagonism attenuates obesity-induced hypertension and glomerular
      hyperfiltration.
AB  - This study examined the importance of aldosterone (ALDO) in mediating changes in
      renal function and increased mean arterial pressure (MAP) during the development
      of dietary-induced obesity in chronically instrumented dogs. Mean arterial
      pressure, heart rate (HR), and cardiac output (CO) were recorded 24 hours per day
      in lean dogs (n=7) before and after administration of an ALDO antagonist,
      eplerenone (EP) (10 mg/kg twice daily), for 10 days. After 10 days of EP
      treatment, the dogs (n=7) were given a supplement of cooked beef fat for 5 weeks
      while EP was continued. An untreated group (n=6) was fed a high fat diet for 5
      weeks and used as control (C). In lean dogs, EP decreased MAP from 89+/-4 to 84+/
      4 mm Hg and glomerular filtration rate from 67.4+/-6.8 to 53.2+/-4.9 mL/min while
      inducing a small negative Na+ balance (-42+/-12 mEq). Plasma renin activity
      increased from 0.4+/-0.1 to 2.7+/-0.7 ng AI/mL per hour and plasma K+ increased
      from 4.8+/-0.1 to 6.1+/-0.3 mEq/L. After 5 weeks of a high fat diet, body weight
      increased 45% to 53% in EP and C obese dogs. In C dogs, MAP increased by 16+/-3
      mm Hg, compared with only 7+/-1 mm Hg in EPLE dogs. Compared with untreated dogs,
      the EP dogs had smaller increases in CO (18+/-4.6% versus 43+/-1.5%), HR (33+/-5%
      versus 60+/-3%), glomerular filtration rate (19+/-5% versus 38+/-6%), and
      cumulative Na+ balance (138+/-35 mEq versus 472+/-110 mEq) after 5 weeks of a
      high fat diet. Thus, EP markedly attenuated glomerular hyperfiltration, sodium
      retention, and hypertension associated with chronic dietary-induced obesity.
      These observations indicate that ALDO plays an important role in the pathogenesis
      of obesity hypertension.

PMID- 14638628
TI  - Innate protection conferred by fucosylated oligosaccharides of human milk against
      diarrhea in breastfed infants.
AB  - To test the hypothesis that human milk fucosyloligosaccharides are part of an
      innate immune system, we addressed whether their expression (1) depends on
      maternal genotype and (2) protects breastfed infants from pathogens. Thus the
      relationship between maternal Lewis blood group type and milk oligosaccharide
      expression and between variable oligosaccharide expression and risk of diarrhea
      in their infants was studied in a cohort of 93 Mexican breastfeeding mother
      infant pairs. Milk of the 67 Le(a-b+) mothers contained more LNF-II (Le(a)) and 3
      FL (Le(x)) (oligosaccharides whose fucose is exclusively alpha 1,3- or alpha 1,4
      linked) than milk from the 24 Le(a-b-) mothers; milk from Le(a-b-) mothers
      contained more LNF-I (H-1) and 2'-FL (H-2), whose fucose is exclusively alpha 1,2
      linked. The pattern of oligosaccharides varied among milk samples; in each milk
      sample, the pattern was summarized as a ratio of 2-linked to non-2-linked
      fucosyloligosaccharides. Milks with the highest ratios were produced primarily by
      Le(a-b-) mothers; those with the lowest ratios were produced exclusively by Le(a
      b+) mothers (p<0.001). Thus maternal genetic polymorphisms expressed as Lewis
      blood group types are expressed in milk as varied fucosyloligosaccharide ratios.
      The four infants who developed diarrhea associated with stable toxin of
      Escherichia coli were consuming milk with lower ratios (4.4 +/- 0.8 [SE]) than
      the remaining infants (8.5 +/- 0.8; p<0.001). Furthermore, the 27 infants who
      developed moderate to severe diarrhea of any cause were consuming milk with lower
      ratios (6.1 +/- 0.9) than the 26 who remained healthy (10.5 +/- 1.9; p = 0.042).
      Thus, milk with higher 2-linked to non-2-linked fucosyloligosaccharide ratios
      affords greater protection against infant diarrhea. We conclude that specific
      oligosaccharides constitute a major element of an innate immune system of human
      milk.

PMID- 14638629
TI  - The parasitic trematode Fasciola hepatica exhibits mammalian-type glycolipids as
      well as Gal(beta1-6)Gal-terminating glycolipids that account for cestode
      serological cross-reactivity.
AB  - Neutral glycosphingolipids from sheep-derived Fasciola hepatica liver flukes were
      isolated and characterized both structurally and serologically. After HPLC
      fractionation, glycolipids were analyzed by linkage analysis, enzymatic cleavage,
      and MALDI-TOF as well as electrospray ionization mass spectrometry. Obtained
      results revealed the presence of two types of neutral glycolipids. The first
      group represented mammalian-type species comprising globo- and
      isoglobotriaosylceramides (Gal(alpha1-4)Gal(beta1-4)Glc(1-1)ceramide and
      Gal(alpha1-3)Gal(beta1-4)Glc(1-1)ceramide, respectively) as well as Forssman
      antigen (GalNAc(alpha1-3)GalNAc(beta1-3/4)Gal(alpha1-4/3)Gal(beta1-4)Glc(1
      1)ceramide). Applying Helix pomatia agglutinin, recognizing terminal alpha-linked
      GalNAc, to cryosections of adult flukes, the latter glycolipid could be localized
      to the F. hepatica gut. As Forssman antigen from the parasite and sheep host led
      to identical MALDI-TOF MS profiles, this glycolipid might be acquired from the
      definitive host. As a second group, highly antigenic glycolipids were
      structurally characterized as Gal(beta1-6)Gal(beta1-4)Glc(1-1)ceramide, Gal(beta1
      6)Gal(alpha1-3/4)Gal(beta1-4)Glc(1-1)ceramide and Gal(beta1-6)Gal(beta1
      6)Gal(alpha1-3/4)Gal(beta1-4)Glc(1-1)ceramide, the latter two structures of which
      exhibited both isoglobo- or globo-series core structures. Terminal Gal(beta1
      6)Gal1-motifs have previously been shown to represent antigenic epitopes of
      neogala-series glycosphingolipids from tape worms. Using human Echinococcus
      granulosus infection sera, Gal(beta1-6)Gal-terminating glycolipids could be
      allocated to the gut in adult liver fluke cryosections. Corresponding neogala
      reactive antibodies in F. hepatica infection serum were detected by their binding
      to E. granulosus and Taenia crassiceps neogala-glycosphingolipids. These
      antibodies might contribute to the known serological cross-reactivity between F.
      hepatica and parasitic cestode infections.

PMID- 14638630
TI  - Intact cell adhesion to glycan microarrays.
AB  - A rapid and reproducible method was developed to detect and quantify carbohydrate
      mediated cell adhesion to glycans arrayed on glass slides. Monosaccharides and
      oligosaccharides were covalently attached to glass slides in 1.7-mm-diameter
      spots (200 spots/slide) separated by a Teflon gasket. Primary chicken
      hepatocytes, which constitutively express a C-type lectin that binds to
      nonreducing terminal N-acetylglucosamine residues, were labeled with a
      fluorescent dye and incubated in 1.3-microL aliquots on the glycosylated spots.
      After incubating to allow cell adhesion, nonadherent cells were removed by
      immersing the slide in phosphate buffered saline, inverting, and centrifuging in
      a sealed custom acrylic chamber so that cells on the derivatized spots were
      subjected to a uniform and controlled centrifugal detachment force while avoiding
      an air-liquid interface. After centrifugation, adherent cells were fixed in place
      and detected by fluorescent imaging. Chicken hepatocytes bound to nonreducing
      terminal GlcNAc residues in different linkages and orientations but not to
      nonreducing terminal galactose or N-acetylgalactosamine residues. Addition of
      soluble GlcNAc (but not Gal) prior to incubation reduced cell adhesion to
      background levels. Extension of the method to CD4+ human T-cells on a 45-glycan
      diversity array revealed specific adhesion to the sialyl Lewis x structure. The
      described method is a robust approach to quantify selective cell adhesion using a
      wide variety of glycans and may contribute to the repertoire of tools for the
      study of glycomics.

PMID- 14638631
TI  - Galectin-1, a cell adhesion modulator, induces apoptosis of rat Leydig cells in
      vitro.
AB  - Galectin-1 (Gal-1), a beta galactoside-binding lectin, is involved in multiple
      biological functions, such as cell adhesion, apoptosis, and metastasis. On the
      basis of its ability to interact with extracellular matrix (ECM) glycoproteins,
      we investigated the Gal-1 effect on Leydig cells, which express and are
      influenced by ECM proteins. In this study, Gal-1 was identified in Leydig cell
      cultures by immunofluorescence. To gain insight into its biological role, Gal-1
      was added to purified rat Leydig cells, under both basal and human chorionic
      gonadotrophin-stimulated conditions. Substantial morphological changes were
      observed, and cell viability showed an 80% decrease after 24 h culture. As a
      functional consequence of Gal-1 addition, testosterone production was reduced in
      a dose-dependent fashion, reaching a minimum of 26% after 24 h compared with
      basal values. cAMP showed a similar variation after 3 h. Assessment of DNA
      hypodiploidy and caspase activity determinations indicated that the reduction in
      viability and in steroidogenesis was caused by apoptosis induced by Gal-1.
      Besides, addition of Gal-1 caused Leydig cell detachment. Presence of laminin-1
      or lactose prevented the effect of Gal-1, suggesting that the carbohydrate
      recognition domain is involved in inducing apoptosis. These findings demonstrate
      a novel mechanism, based on Gal-1 and laminin-1 interaction, which could help us
      better understand the molecular basis of Leydig cell function and survival
      control.

PMID- 14638632
TI  - Studies on gangliosides with affinity for Helicobacter pylori: binding to natural
      and chemically modified structures.
AB  - Helicobacter pylori, like many other microbes, has the ability to bind to
      carbohydrate epitopes. Several sugar sequences have been reported as active for
      the bacterium, including some neutral, sulfated, and sialylated structures. We
      investigated structural requirements for the sialic acid-dependent binding using
      a number of natural and chemically modified gangliosides. We have chosen for
      derivatization studies two kinds of binding-active glycolipids, the simple
      ganglioside S-3PG (Neu5Ac alpha 3Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer,
      sialylparagloboside) and branched polyglycosylceramides (PGCs) of human origin.
      The modifications included oxidation of the sialic acid glycerol chain, reduction
      of the carboxyl group, amidation of the carboxyl group, and lactonization.
      Binding experiments confirmed a preference of H. pylori for 3-linked sialic acid
      and penultimate 4-linked galactose. As expected, neolacto gangliosides (with Gal
      beta 4GlcNAc in the core structure) were active in our assays, whereas
      gangliosides with lacto (Gal beta 3GlcNAc) and ganglio (Gal beta 3GalNAc)
      carbohydrate chains were not. Negative binding results were also obtained for
      disialylparagloboside (with terminal NeuAc alpha 8NeuAc) and NeuAc alpha 6
      containing glycolipids. Chemical studies revealed dependence of the binding on
      Neu5Ac and its glycerol and carboxyl side chains. Most of the derivatizations
      performed on these groups abolished the binding; however, some of the amide forms
      turned out to be active, and one of them (octadecylamide) was found to be an
      excellent binder. The combined data from molecular dynamics simulations indicate
      that the binding-active configuration of the terminal disaccharide of S-3PG is
      with the sialic acid in the anticlinal conformation, whereas in branched PGCs the
      same structural element most likely assumes the synclinal presentation.

PMID- 14638633
TI  - Obituary: the Canadian Task Force on Preventive Health Care.

PMID- 14638637
TI  - Pilot study of the defining issues test.

PMID- 14638638
TI  - Armoured brain.

PMID- 14638640
TI  - MCC evaluating examination and the international medical graduate.

PMID- 14638642
TI  - Ziprasidone--not an option for serotonin syndrome.

PMID- 14638644
TI  - SARS in health care workers.

PMID- 14638645
TI  - Anaphylaxis treatment: the details.

PMID- 14638647
TI  - Anaphylaxis treatment: the details.

PMID- 14638648
TI  - The use of cholesterol-lowering medications after coronary revascularization.
AB  - BACKGROUND: In clinical trials, cholesterol-lowering medications have been proven
      to decrease mortality and morbidity and are strongly recommended as secondary
      prevention for patients with established coronary artery disease. Whether
      physicians and patients follow this recommendation is unknown. Our objective was
      to determine the rate at which patients fill at least one prescription for
      cholesterol-lowering medications after coronary revascularization. METHODS: Using
      the computerized administrative databases of the Regie de l'assurance maladie du
      Quebec, we identified all elderly patients (older than 65 years) who had a
      coronary revascularization procedure (percutaneous coronary intervention or
      coronary artery bypass graft) between Apr. 1, 1995, and Dec. 31, 1997, and who
      survived until hospital discharge. We also determined the percentage of these
      patients who filled one or more prescriptions for cholesterol-lowering drug
      therapy before Dec. 31, 1999, or death, whichever date came first. We used
      multivariate logistic regression models to examine the independent associations
      between filling a prescription for a cholesterol-lowering drug, patient
      characteristics and the type and year of coronary revascularization. RESULTS: We
      identified 11 958 elderly patients who had a coronary revascularization between
      Apr. 1, 1995, and Dec. 31, 1997. During a follow-up period that averaged 3 years,
      4443 (37.2%) patients did not fill a prescription for a cholesterol-lowering
      medication. Patients who were male, of advanced age, who had diabetes or
      congestive heart failure were less likely to fill a prescription for a
      cholesterol-lowering medication. Patients whose initial revascularization
      procedure was coronary artery bypass grafting were also less likely than those
      who had angioplasty to start cholesterol-lowering medication (relative risk [RR]
      0.77, 95% confidence interval [CI] 0.73 - 0.81). Use of cholesterol lowering
      medications before the revascularization procedure was very strongly associated
      with future drug use (RR 7.20, 95% CI 6.83-7.58). INTERPRETATION: In this
      population-based study of revascularized patients, we observed a substantial
      underutilization of cholesterol-lowering medications after revascularization. Our
      observations suggest an important role for continuity of care in the treatment of
      cardiovascular patients undergoing revascularization procedures.

PMID- 14638649
TI  - Sale of kava extract in some health food stores.
AB  - January 2002, Health Canada issued an advisory, followed by a ban in August 2002,
      on the sale of herbal kava. One month after the advisory, 22 (67%) of 33 health
      food stores approached were selling kava. Two months after the ban, 17 (57%) of
      30 stores continued to sell kava. These findings demonstrate that health food
      stores may need to be better informed about the sale of restricted natural health
      products.

PMID- 14638650
TI  - Kava: a test case for Canada's new approach to natural health products.

PMID- 14638651
TI  - Antiviral treatment of SARS: can we draw any conclusions?

PMID- 14638652
TI  - Gaps in the evaluation and monitoring of new pharmaceuticals: proposal for a
      different approach.

PMID- 14638653
TI  - Why don't we initiate more large simple randomized controlled trials?

PMID- 14638654
TI  - Rehabilitation medicine: 3. Management of adult spasticity.
AB  - Spasticity refers to an abnormal, velocity-dependent (i.e., how fast the joint is
      moved through its range) increase in muscle tone resulting from interruption of
      the neural circuitry regulating the muscles and is a common complication of
      cerebral palsy, brain injuries, spinal cord injuries, multiple sclerosis and
      stroke. The muscle stretch reflex is thought to play an important role in
      spasticity generation. Spasticity can have a significant detrimental effect on
      daily functions, such as feeding, dressing, hygiene, bladder and bowel control,
      and mobility; patients' need for support can also influence the cost of care.
      Thus, managing these patients appropriately or referring them to those with
      expertise in this area is important. In this article, I review the
      pathophysiology of spasticity and the evaluation and management of adult patients
      with the condition. Two hypothetical cases are presented to illustrate the
      management of spasticity.

PMID- 14638655
TI  - Fetal alcohol spectrum disorder.

PMID- 14638656
TI  - Seasonal drinking: let's avoid the "January effect".

PMID- 14638657
TI  - Nefazodone (Serzone) withdrawn because of hepatotoxicity.

PMID- 14638658
TI  - Does the choice of beta-blocker affect outcome in chronic heart failure?

PMID- 14638659
TI  - The mystery of the broken bones.

PMID- 14638664
TI  - Residency crisis in offing, provinces warned.

PMID- 14638665
TI  - Drive thru, prevent flu.

PMID- 14638666
TI  - Israel assumes unwanted role as world leader in disaster management.

PMID- 14638669
TI  - Lack of answers concerns MDs as privacy law deadline nears.

PMID- 14638670
TI  - Should drug companies be allowed to sponsor Cochrane reviews?

PMID- 14638672
TI  - Bupropion: 1 drug, 4 different brand names.

PMID- 14638673
TI  - RSI placing a strain on workplace.

PMID- 14638676
TI  - A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae
      mediator subunit Cse2.
AB  - The multiprotein Mediator complex is a coactivator required for activation of RNA
      polymerase II transcription by DNA bound transcription factors. We previously
      identified and partially purified a mammalian Mediator complex from rat liver
      nuclei (Brower, C.S., Sato, S., Tomomori-Sato, C., Kamura, T., Pause, A.,
      Stearman, R., Klausner, R.D., Malik, S., Lane, W.S., Sorokina, I., Roeder, R.G.,
      Conaway, J.W., and Conaway, R.C. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 10353
      10358). Analysis by tandem mass spectrometry of proteins present in the most
      highly purified rat Mediator fractions led to the identification of a collection
      of new mammalian Mediator subunits, as well as several potential Mediator
      subunits including a previously uncharacterized protein encoded by the FLJ10193
      open reading frame. In this study, we present direct biochemical evidence that
      the FLJ10193 protein, which we designate Med25, is a bona fide subunit of the
      mammalian Mediator complex. In addition, we present evidence that Med25 shares
      structural and functional properties with Saccharomyces cerevisiae Mediator
      subunit Cse2 and may be a mammalian Cse2 ortholog. Taken together, our findings
      identify a novel mammalian Mediator subunit and shed new light on the
      architecture of the mammalian Mediator complex.

PMID- 14638677
TI  - Negatively charged amino acids within the intraluminal loop of ryanodine receptor
      are involved in the interaction with triadin.
AB  - In mammalian striated muscles, ryanodine receptor (RyR), triadin, junctin, and
      calsequestrin form a quaternary complex in the lumen of sarcoplasmic reticulum.
      Such intermolecular interactions contribute not only to the passive buffering of
      sarcoplasmic reticulum luminal Ca2+, but also to the active Ca2+ release process
      during excitation-contraction coupling. Here we tested the hypothesis that
      specific charged amino acids within the luminal portion of RyR mediate its direct
      interaction with triadin. Using in vitro binding assay and site-directed
      mutagenesis, we found that the second intraluminal loop of the skeletal muscle
      RyR1 (amino acids 4860-4917), but not the first intraluminal loop of RyR1 (amino
      acids 4581-4640) could bind triadin. Specifically, three negatively charged
      residues Asp4878, Asp4907, and Glu4908 appear to be critical for the association
      with triadin. Using deletional approaches, we showed that a KEKE motif of triadin
      (amino acids 200-232) is essential for the binding to RyR1. Because the second
      intraluminal loop of RyR has been previously shown to contain the ion-conducting
      pore as well as the selectivity filter of the Ca2+ release channel, and Asp4878,
      Asp4907, and Glu4908 residues are predicted to locate at the periphery of the
      pore assembly of the channel, our data suggest that a physical interaction
      between RyR1 and triadin could play an active role in the overall Ca2+ release
      process of excitation-contraction coupling in muscle cells.

PMID- 14638678
TI  - Fatty aldehyde dehydrogenase: potential role in oxidative stress protection and
      regulation of its gene expression by insulin.
AB  - Phosphatidylinositol 3-kinase signaling regulates the expression of several genes
      involved in lipid and glucose homeostasis; deregulation of these genes may
      contribute to insulin resistance and progression toward type 2 diabetes. By
      employing RNA arbitrarily primed-PCR to search for novel phosphatidylinositol 3
      kinase-regulated genes in response to insulin in isolated rat adipocytes, we
      identified fatty aldehyde dehydrogenase (FALDH), a key component of the
      detoxification pathway of aldehydes arising from lipid peroxidation events. Among
      these latter events are oxidative stresses associated with insulin resistance and
      diabetes. Upon insulin injection, FALDH mRNA expression increased in rat liver
      and white adipose tissue and was impaired in two models of insulin-resistant
      mice, db/db and high fat diet mice. FALDH mRNA levels were 4-fold decreased in
      streptozotocin-treated rats, suggesting that FALDH deregulation occurs both in
      hyperinsulinemic insulin-resistant state and hypoinsulinemic type 1 diabetes
      models. Moreover, insulin treatment increases FALDH activity in hepatocytes, and
      expression of FALDH was augmented during adipocyte differentiation. Considering
      the detoxifying role of FALDH, its deregulation in insulin-resistant and type 1
      diabetic models may contribute to the lipid-derived oxidative stress. To assess
      the role of FALDH in the detoxification of oxidized lipid species, we evaluated
      the production of reactive oxygen species in normal versus FALDH-overexpressing
      adipocytes. Ectopic expression of FALDH significantly decreased reactive oxygen
      species production in cells treated by 4-hydroxynonenal, the major lipid
      peroxidation product, suggesting that FALDH protects against oxidative stress
      associated with lipid peroxidation. Taken together, our observations illustrate
      the importance of FALDH in insulin action and its deregulation in states
      associated with altered insulin signaling.

PMID- 14638679
TI  - Synergy between conserved ABC signature Ser residues in P-glycoprotein catalysis.
AB  - Functional roles of the two ABC signature sequences ("LSGGQ") in the N- and C
      terminal nucleotide binding domains of P-glycoprotein were studied by mutating
      the conserved Ser residues to Ala. The two single mutants (S528A; S1173A) each
      impaired ATPase activity mildly, and showed generally symmetrical effects on
      function, consistent with equivalent mechanistic roles of the two nucleotide
      sites. Synergy between the two mutations when combined was remarkable and
      resulted in strong catalytic impairment. The Ser residues are not involved
      significantly in MgATP- or MgADP-binding or in interdomain communication between
      catalytic sites and drug binding sites. Retention of product MgADP is not the
      cause of reduced turnover. Mutation of Ser to Ala reduced the strength of
      interaction with the chemical transition state specifically, as shown by vanadate
      ADP and beryllium fluoride-ADP trapping experiments. Therefore, the two conserved
      ABC signature motif Ser residues of P-glycoprotein cooperatively accelerate ATP
      hydrolysis via chemical transition state interaction. Because the transition
      state complex is currently believed to form in the dimerized state of the
      nucleotide binding domains, one may also conclude that both Ser-OH are necessary
      for correct formation of the dimer state.

PMID- 14638680
TI  - SK3-1C, a dominant-negative suppressor of SKCa and IKCa channels.
AB  - Small conductance Ca2+-activated K+ channels, products of the SK1-SK3 genes,
      regulate membrane excitability both within and outside the nervous system. We
      report the characterization of a SK3 variant (SK3-1C) that differs from SK3 by
      utilizing an alternative first exon (exon 1C) in place of exon 1A used by SK3,
      but is otherwise identical to SK3. Quantitative RT-PCR detected abundant
      expression of SK3-1C transcripts in human lymphoid tissues, skeletal muscle,
      trachea, and salivary gland but not the nervous system. SK3-1C did not produce
      functional channels when expressed alone in mammalian cells, but suppressed SK1,
      SK2, SK3, and IKCa1 channels, but not BKCa or KV channels. Confocal microscopy
      revealed that SK3-1C sequestered SK3 protein intracellularly. Dominant-inhibitory
      activity of SK3-1C was not due to a nonspecific calmodulin sponge effect since
      overexpression of calmodulin did not reverse SK3-1C-mediated intracellular
      trapping of SK3 protein, and calmodulin-Ca2+-dependent inactivation of CaV
      channels was not affected by SK3-1C overexpression. Deletion analysis identified
      a dominant-inhibitory segment in the SK3-1C C terminus that resembles
      tetramerization-coiled-coiled domains reported to enhance tetramer stability and
      selectivity of multimerization of many K+ channels. SK3-1C may therefore suppress
      calmodulin-gated SKCa/IKCa channels by trapping these channel proteins
      intracellularly via subunit interactions mediated by the dominant-inhibitory
      segment and thereby reduce functional channel expression on the cell surface.
      Such family-wide dominant-negative suppression by SK3-1C provides a powerful
      mechanism to titrate membrane excitability and is a useful approach to define the
      functional in vivo role of these channels in diverse tissues by their targeted
      silencing.

PMID- 14638681
TI  - Estrogen receptor inhibits c-Jun-dependent stress-induced cell death by binding
      and modifying c-Jun activity in human breast cancer cells.
AB  - c-Jun, a major component of the AP-1 transcription factor, is either pro- or anti
      apoptotic with cellular determinants unknown. Nuclear estrogen receptor (ER), on
      the other hand, regulates gene expression through both estrogen response elements
      and AP-1. Here we show that stress stimulates c-Jun phosphorylation and AP-1
      activity in both ER+ and ER- human breast cancer cells and only induces cell
      death in ER- cells, indicating a determinant role of ER in c-Jun/AP-1 activity.
      The inhibitory effect of ER in stress-induced cell death is confirmed by ER
      transfection into ER- cells. Furthermore, inhibition of c-Jun activation by a
      dominant negative c-Jun blocks AP-1 activity in ER+ cells and attenuates stress
      induced cell death but not AP-1 activity in ER- cells, suggesting that the c
      Jun/AP-1 activity has distinct properties depending on ER status. ER was shown to
      inhibit stress-induced cell death through its physical interaction with c-Jun.
      This is because ER binds c-Jun in breast cancer cells, stress treatment further
      increases the ER-bound phosphorylated c-Jun, and the c-Jun binding-deficient ER
      mutant fails to protect stress-induced cell death. Together, our studies reveal a
      novel function of ER in stress response by modification of c-Jun activity.

PMID- 14638682
TI  - Delta-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous
      versus imported.
AB  - The heme biosynthetic pathway of the malaria parasite is a drug target and the
      import of host delta-aminolevulinate dehydratase (ALAD), the second enzyme of the
      pathway, from the red cell cytoplasm by the intra erythrocytic malaria parasite
      has been demonstrated earlier in this laboratory. In this study, ALAD encoded by
      the Plasmodium falciparum genome (PfALAD) has been cloned, the protein
      overexpressed in Escherichia coli, and then characterized. The mature recombinant
      enzyme (rPfALAD) is enzymatically active and behaves as an octamer with a subunit
      Mr of 46,000. The enzyme has an alkaline pH optimum of 8.0 to 9.0. rPfALAD does
      not require any metal ion for activity, although it is stimulated by 20-30% upon
      addition of Mg2+. The enzyme is inhibited by Zn2+ and succinylacetone. The
      presence of PfALAD in P. falciparum can be demonstrated by Western blot analysis
      and immunoelectron microscopy. The enzyme has been localized to the apicoplast of
      the malaria parasite. Homology modeling studies reveal that PfALAD is very
      similar to the enzyme species from Pseudomonas aeruginosa, but manifests features
      that are unique and different from plant ALADs as well as from those of the
      bacterium. It is concluded that PfALAD, while resembling plant ALADs in terms of
      its alkaline pH optimum and apicoplast localization, differs in its Mg2+
      independence for catalytic activity or octamer stabilization. Expression levels
      of PfALAD in P. falciparum, based on Western blot analysis, immunoelectron
      microscopy, and EDTA-resistant enzyme activity assay reveals that it may account
      for about 10% of the total ALAD activity in the parasite, the rest being
      accounted for by the host enzyme imported by the parasite. It is proposed that
      the role of PfALAD may be confined to heme synthesis in the apicoplast that may
      not account for the total de novo heme biosynthesis in the parasite.

PMID- 14638683
TI  - Synergistic effects of coactivators GRIP1 and beta-catenin on gene activation:
      cross-talk between androgen receptor and Wnt signaling pathways.
AB  - The p160 coactivators, such as GRIP1, bind nuclear receptors and help to mediate
      transcriptional activation. beta-Catenin binds to and serves as a coactivator for
      the nuclear receptor, androgen receptor (AR), and the Lymphoid Enhancer Factor/T
      Cell Factor family member, Lef1. Here we report that GRIP1 and beta-catenin can
      bind strongly to each other through the AD2 domain of GRIP1. Furthermore, GRIP1
      and beta-catenin can synergistically enhance the activity of both AR and Lef1,
      and both coactivators are recruited specifically to AR-driven and Lef1-driven
      promoters. However, the mechanism of beta-catenin-GRIP1 coactivator function and
      synergy is different with AR and Lef1. While beta-catenin can bind directly to
      both AR and Lef1, GRIP1 can only bind directly to AR; the ability of GRIP1 to
      associate with and function as a coactivator for Lef1 is entirely dependent on
      the presence of beta-catenin. Thus, whereas GRIP1 coactivator function involves
      direct binding to nuclear receptors and most other classes of DNA-binding
      transcriptional activator proteins, the coactivator function of GRIP1 with Lef1
      follows a novel paradigm where GRIP1 is recruited indirectly to Lef1 through
      their mutual association with beta-catenin. The beta-catenin-GRIP1 interaction
      represents another potential point of cross-talk between the AR and Wnt signaling
      pathways.

PMID- 14638684
TI  - Amino acid substitution at the dimeric interface of human manganese superoxide
      dismutase.
AB  - The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer
      human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the
      dimer interface and participate in a hydrogen-bonded network that extends to the
      active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N,
      Y166F, and the corresponding double mutant showed 10-fold decreases in steady
      state constants for catalysis measured by pulse radiolysis. The observation of no
      additional effect upon the second mutation is an example of cooperatively
      interacting residues. A similar effect was observed in the thermal stability of
      these enzymes; the double mutant did not reduce the major unfolding transition to
      an extent greater than either single mutant. The crystal structures of these site
      specific mutants each have unique conformational changes, but each has lost the
      hydrogen bond across the dimer interface, which results in a decrease in
      catalysis. These same mutations caused an enhancement of the dissociation of the
      product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to
      prolong the lifetime of the inhibited complex. This would have a selective
      advantage in blocking a cellular overproduction of toxic H2O2.

PMID- 14638685
TI  - Identification of formaldehyde-induced modifications in proteins: reactions with
      model peptides.
AB  - Formaldehyde is a well known cross-linking agent that can inactivate, stabilize,
      or immobilize proteins. The purpose of this study was to map the chemical
      modifications occurring on each natural amino acid residue caused by
      formaldehyde. Therefore, model peptides were treated with excess formaldehyde,
      and the reaction products were analyzed by liquid chromatography-mass
      spectrometry. Formaldehyde was shown to react with the amino group of the N
      terminal amino acid residue and the side-chains of arginine, cysteine, histidine,
      and lysine residues. Depending on the peptide sequence, methylol groups, Schiff
      bases, and methylene bridges were formed. To study intermolecular cross-linking
      in more detail, cyanoborohydride or glycine was added to the reaction solution.
      The use of cyanoborohydride could easily distinguish between peptides containing
      a Schiff-base or a methylene bridge. Formaldehyde and glycine formed a Schiff
      base adduct, which was rapidly attached to primary N-terminal amino groups,
      arginine and tyrosine residues, and, to a lesser degree, asparagine, glutamine,
      histidine, and tryptophan residues. Unexpected modifications were found in
      peptides containing a free N-terminal amino group or an arginine residue.
      Formaldehyde-glycine adducts reacted with the N terminus by means of two steps:
      the N terminus formed an imidazolidinone, and then the glycine was attached via a
      methylene bridge. Two covalent modifications occurred on an arginine-containing
      peptide: (i) the attachment of one glycine molecule to the arginine residue via
      two methylene bridges, and (ii) the coupling of two glycine molecules via four
      methylene bridges. Remarkably, formaldehyde did not generate intermolecular cross
      links between two primary amino groups. In conclusion, the use of model peptides
      enabled us to determine the reactivity of each particular cross-link reaction as
      a function of the reaction conditions and to identify new reaction products after
      incubation with formaldehyde.

PMID- 14638686
TI  - Suppression of macrophage eicosanoid synthesis by atherogenic lipoproteins is
      profoundly affected by cholesterol-fatty acyl esterification and the Niemann-Pick
      C pathway of lipid trafficking.
AB  - Atheroma macrophages internalize large quantities of lipoprotein-derived lipids.
      While most emphasis has been placed on cholesterol, lipoprotein-derived fatty
      acids may also play important roles in lesional macrophage biology. Little is
      known, however, about the trafficking or metabolism of these fatty acids. In this
      study, we first show that the cholesterol-fatty acyl esterification reaction,
      catalyzed by acyl-CoA:cholesterol acyltransferase (ACAT), competes for the
      incorporation of lipoprotein-derived fatty acids into cellular phospholipids.
      Furthermore, conditions that inhibit trafficking of cholesterol from late
      endosomes/lysosomes to the endoplasmic reticulum (ER), such as the amphipathic
      amine U18666A and the Npc1+/- mutation, also inhibit incorporation of lipoprotein
      derived fatty acids into phospholipids. The biological relevance of these
      findings was investigated by studying the suppression of agonist-induced
      prostaglandin E(2) (PGE(2)) and leukotriene C(4)/D(4)/E(4) production during
      lipoprotein uptake by macrophages, which has been postulated to involve
      enrichment of cellular phospholipids with non-arachidonic fatty acids (NAAFAs).
      We found that eicosanoid suppression was markedly enhanced when ACAT was
      inhibited and prevented when late endosomal/lysosomal lipid trafficking was
      blocked. Moreover, PGE(2) suppression depended entirely on acetyl-LDL-derived
      NAAFAs, not on acetyl-LDL-cholesterol, and was not due to decreased cPLA(2)
      activity per se. These data support the following model: lipoprotein-derived
      NAAFAs traffic via the NPC1 pathway from late endosomes/lysosomes to a critical
      pool of phospholipids. In competing reactions, these NAAFAs can be either
      esterified to cholesterol or incorporated into phospholipids, resulting in
      suppression of eicosanoid biosynthesis. In view of recent evidence suggesting
      dysfunctional cholesterol esterification in late lesional macrophages, these data
      predict that such cells would have highly suppressed eicosanoid synthesis, thus
      affecting eicosanoid-mediated cell signaling in advanced atherosclerosis.

PMID- 14638687
TI  - Contribution of the Per/Arnt/Sim (PAS) domains to DNA binding by the basic helix
      loop-helix PAS transcriptional regulators.
AB  - The basic helix-loop-helix (bHLH) PAS transcriptional regulators control critical
      developmental and metabolic processes, including transcriptional responses to
      stimuli such as hypoxia and environmental pollutants, mediated respectively by
      hypoxia inducible factors (HIF-alpha) and the dioxin (aryl hydrocarbon) receptor
      (DR). The bHLH proteins contain a basic DNA binding sequence adjacent to a helix
      loop-helix dimerization domain. Dimerization among bHLH.PAS proteins is
      additionally regulated by the PAS region, which controls the specificity of
      partner choice such that HIF-alpha and DR must dimerize with the aryl hydrocarbon
      nuclear translocator (Arnt) to form functional DNA binding complexes. Here, we
      have analyzed purified bacterially expressed proteins encompassing the N-terminal
      bHLH and bHLH.PAS regions of Arnt, DR, and HIF-1alpha and evaluated the
      contribution of the PAS domains to DNA binding in vitro. Recovery of functional
      DNA binding proteins from bacteria was dramatically enhanced by coexpression of
      the bHLH.PAS regions of DR or HIF-1alpha with the corresponding region of Arnt.
      Formation of stable protein-DNA complexes by DR/Arnt and HIF-1alpha/Arnt
      heterodimers with their cognate DNA sequences required the PAS A domains and
      exhibited KD values of 0.4 nM and approximately 50 nM, respectively. In contrast,
      the presence of the PAS domains of Arnt had little effect on DNA binding by Arnt
      homodimers, and these bound DNA with a KD of 45 nM. In the case of the DR, both
      high affinity DNA binding and dimer stability were specific to its native PAS
      domain, since a chimera in which the PAS A domain was substituted with the
      equivalent domain of Arnt generated a destabilized protein that bound DNA poorly.

PMID- 14638688
TI  - Structural and enzymatic analysis of soybean beta-amylase mutants with increased
      pH optimum.
AB  - Comparison of the architecture around the active site of soybean beta-amylase and
      Bacillus cereus beta-amylase showed that the hydrogen bond networks (Glu380
      (Lys295-Met51) and Glu380-Asn340-Glu178) in soybean beta-amylase around the base
      catalytic residue, Glu380, seem to contribute to the lower pH optimum of soybean
      beta-amylase. To convert the pH optimum of soybean beta-amylase (pH 5.4) to that
      of the bacterial type enzyme (pH 6.7), three mutants of soybean beta-amylase,
      M51T, E178Y, and N340T, were constructed such that the hydrogen bond networks
      were removed by site-directed mutagenesis. The kinetic analysis showed that the
      pH optimum of all mutants shifted dramatically to a neutral pH (range, from 5.4
      to 6.0-6.6). The Km values of the mutants were almost the same as that of soybean
      beta-amylase except in the case of M51T, while the Vmax values of all mutants
      were low compared with that of soybean beta-amylase. The crystal structure
      analysis of the wild type-maltose and mutant-maltose complexes showed that the
      direct hydrogen bond between Glu380 and Asn340 was completely disrupted in the
      mutants M51T, E178Y, and N340T. In the case of M51T, the hydrogen bond between
      Glu380 and Lys295 was also disrupted. These results indicated that the reduced
      pKa value of Glu380 is stabilized by the hydrogen bond network and is responsible
      for the lower pH optimum of soybean beta-amylase compared with that of the
      bacterial beta-amylase.

PMID- 14638689
TI  - S100A1 is a novel molecular chaperone and a member of the Hsp70/Hsp90
      multichaperone complex.
AB  - Although calmodulin is known to be a component of the Hsp70/Hsp90 multichaperone
      complex, the functional role of the protein remains uncertain. In this study, we
      have identified S100A1, but not calmodulin or other S100 proteins, as a potent
      molecular chaperone and a new member of the multichaperone complex. Glutathione S
      transferase pull-down assays and co-immunoprecipitation experiments indicated the
      formation of stable complexes between S100A1 and Hsp90, Hsp70, FKBP52, and CyP40
      both in vitro and in mammalian cells. S100A1 potently protected citrate synthase,
      aldolase, glyceraldehyde-3-phosphate dehydrogenase, and rhodanese from heat
      induced aggregation and suppressed the aggregation of chemically denatured
      rhodanese and citrate synthase during the refolding pathway. In addition, S100A1
      suppressed the heat-induced inactivation of citrate synthase activity, similar to
      that for Hsp90 and p23. The chaperone activity of S100A1 was antagonized by
      calmodulin antagonists, such as fluphenazine and prenylamine, that is, indeed an
      intrinsic function of the protein. The overexpression of S100A1 in COS-7 cells
      protected transiently expressed firefly luciferase and Escherichia coli beta
      galactosidase from inactivation during heat shock. The results demonstrate a
      novel physiological function for S100A1 and bring us closer to a comprehensive
      understanding of the molecular mechanisms of the Hsp70/Hsp90 multichaperone
      complex.

PMID- 14638690
TI  - Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin
      chains catalyzed by BRCA1-BARD1 ubiquitin ligase.
AB  - The breast and ovarian cancer suppressor BRCA1 acquires significant ubiquitin
      ligase activity when bound to BARD1 as a RING heterodimer. Although the activity
      may well be important for the role of BRCA1 as a tumor suppressor, the
      biochemical consequence of the activity is not yet known. Here we report that
      BRCA1-BARD1 catalyzes Lys-6-linked polyubiquitin chain formation. K6R mutation of
      ubiquitin dramatically reduces the polyubiquitin products mediated by BRCA1-BARD1
      in vitro. BRCA1-BARD1 preferentially utilizes ubiquitin with a single Lys residue
      at Lys-6 or Lys-29 to mediate autoubiquitination of BRCA1 in vivo. Furthermore,
      mass spectrometry analysis identified the Lys-6-linked branched ubiquitin
      fragment from the polyubiquitin chain produced by BRCA1-BARD1 using wild type
      ubiquitin. The BRCA1-BARD1-mediated Lys-6-linked polyubiquitin chains are
      deubiquitinated by 26 S proteasome in vitro, whereas autoubiquitinated CUL1
      through Lys-48-linked polyubiquitin chains is degraded. Proteasome inhibitors do
      not alter the steady state level of the autoubiquitinated BRCA1 in vivo. Hence,
      the results indicate that BRCA1-BARD1 mediates novel polyubiquitin chains that
      may be distinctly edited by 26 S proteasome from conventional Lys-48-linked
      polyubiquitin chains.

PMID- 14638691
TI  - Identification of two distinct pathways of protein kinase Calpha down-regulation
      in intestinal epithelial cells.
AB  - Signal transduction pathways are controlled by desensitization mechanisms, which
      can affect receptors and/or downstream signal transducers. It has long been
      recognized that members of the protein kinase C (PKC) family of signal
      transduction molecules undergo down-regulation in response to activation.
      Previous reports have indicated that key steps in PKCalpha desensitization
      include caveolar internalization, priming site dephosphorylation, ubiquitination
      of the dephosphorylated protein, and degradation by the proteasome. In the
      current study, comparative analysis of PKCalpha processing induced by the PKC
      agonists phorbol 12-myristate 13-acetate and bryostatin 1 in IEC-18 rat
      intestinal epithelial cells demonstrates that: (a) at least two pathways of
      PKCalpha down-regulation can co-exist within cells, and (b) a single PKC agonist
      can activate both pathways at the same time. Using a combined biochemical and
      morphological approach, we identify a novel pathway of PKCalpha desensitization
      that involves ubiquitination of mature, fully phosphorylated activated enzyme at
      the plasma membrane and subsequent down-regulation by the proteasome. The
      phosphatase inhibitors okadaic acid and calyculin A accelerated PKCalpha down
      regulation and inhibitors of vesicular trafficking did not prevent degradation of
      the protein, indicating that neither internalization nor priming site
      dephosphorylation are requisite intermediate steps in this ubiquitin/proteasome
      dependent pathway of PKCalpha down-regulation. Instead, caveolar trafficking and
      dephosphorylation are involved in a second, proteasome-independent mechanism of
      PKCalpha desensitization in this system. Our findings highlight subcellular
      distribution and phosphorylation state as critical determinants of PKCalpha
      desensitization pathways.

PMID- 14638692
TI  - Organization of the cores of the mammalian pyruvate dehydrogenase complex formed
      by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and
      E3 components.
AB  - The subunits of the dihydrolipoyl acetyltransferase (E2) component of mammalian
      pyruvate dehydrogenase complex can form a 60-mer via association of the C
      terminal I domain of E2 at the vertices of a dodecahedron. Exterior to this inner
      core structure, E2 has a pyruvate dehydrogenase component (E1)-binding domain
      followed by two lipoyl domains, all connected by mobile linker regions. The
      assembled core structure of mammalian pyruvate dehydrogenase complex also
      includes the dihydrolipoyl dehydrogenase (E3)-binding protein (E3BP) that binds
      the I domain of E2 by its C-terminal I' domain. E3BP similarly has linker regions
      connecting an E3-binding domain and a lipoyl domain. The composition of E2.E3BP
      was thought to be 60 E2 plus approximately 12 E3BP. We have prepared homogenous
      human components. E2 and E2.E3BP have s(20,w) values of 36 S and 31.8 S,
      respectively. Equilibrium sedimentation and small angle x-ray scattering studies
      indicate that E2.E3BP has lower total mass than E2, and small angle x-ray
      scattering showed that E3 binds to E2.E3BP outside the central dodecahedron. In
      the presence of saturating levels of E1, E2 bound approximately 60 E1 and
      maximally sedimented 64.4 +/- 1.5 S faster than E2, whereas E1-saturated E2.E3BP
      maximally sedimented 49.5 +/- 1.4 S faster than E2.E3BP. Based on the impact on
      sedimentation rates by bound E1, we estimate fewer E1 (approximately 12) were
      bound by E2.E3BP than by E2. The findings of a smaller E2.E3BP mass and a lower
      capacity to bind E1 support the smaller E3BP substituting for E2 subunits rather
      than adding to the 60-mer. We describe a substitution model in which 12 I'
      domains of E3BP replace 12 I domains of E2 by forming 6 dimer edges that are
      symmetrically located in the dodecahedron structure. Twelve E3 dimers were bound
      per E248.E3BP12 mass, which is consistent with this model.

PMID- 14638693
TI  - Evidence for a critical role of the tumor necrosis factor alpha convertase (TACE)
      in ectodomain shedding of the p75 neurotrophin receptor (p75NTR).
AB  - Protein ectodomain shedding, the proteolytic release of the extracellullar domain
      of membrane-tethered proteins, can dramatically affect the function of cell
      surface receptors, growth factors, cytokines, and other proteins. In this study,
      we evaluated the activities involved in ectodomain shedding of p75NTR, a
      neurotrophin receptor with critical roles in neuronal differentiation and
      survival. p75NTR is shed in a variety of cell types, including dorsal root
      ganglia cells and PC12 cells. In Chinese hamster ovary cells, inhibitors of the
      MEK/ERK and p38 MAP kinase pathways uncovered distinct signaling pathways
      required for the constitutive and stimulated shedding of p75NTR. Stimulated
      p75NTR shedding is abrogated in M2 mutant Chinese hamster ovary cells that lack
      functional tumor necrosis factor-alpha converting enzyme (TACE, also referred to
      as ADAM17) and in cells isolated from adam17-/- mice, but not in cells from
      adam9/12/15-/- or adam10-/- mice. Stimulated p75(NTR) shedding is strongly
      reduced by deletion of 15 amino acid residues in its extracellular membrane
      proximal stalk domain. However, similar to other shed proteins, point mutations
      and overlapping shorter deletions within this region have little or no effect on
      shedding. Because ectodomain shedding of p75NTR releases a soluble ectodomain and
      could also be a prerequisite for its regulated intramembrane proteolysis, these
      findings may have important implications for the functional regulation of p75NTR.

PMID- 14638695
TI  - Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac
      dependent cell migration.
AB  - Cell migration is essential throughout embryonic and adult life. In numerous cell
      systems, the small GTPase Rac is required for lamellipodia formation at the
      leading edge and movement ability. However, the molecular mechanisms leading to
      Rac activation during migration are still unclear. Recently, a mammalian
      superfamily of proteins related to the prototype member Dock180 has been
      identified with homologues in Drosophila and Caenorhabditis elegans. Here, we
      addressed the role of Dock180 and ELMO1 proteins, which function as a complex to
      mediate Rac activation, in mammalian cell migration. Using mutants of Dock180 and
      ELMO1 in a Transwell assay as well as transgenic rescue of a C. elegans mutant
      lacking CED-5 (Dock180 homologue), we identified specific regions of Dock180 and
      ELMO1 required for migration in vitro and in a whole animal model. In both
      systems, the Dock180.ELMO1 complex formation and the ability to activate Rac were
      required. We also found that ELMO1 regulated multiple Dock180 superfamily members
      to promote migration. Interestingly, deletion mutants of ELMO1 missing their
      first 531 or first 330 amino acids that can still bind and cooperate with Dock180
      in Rac activation failed to promote migration, which correlated with the
      inability to localize to lamellipodia. This finding suggests that Rac activation
      by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N
      terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a
      role in cell migration.

PMID- 14638694
TI  - H2O2-dependent activation of GCLC-ARE4 reporter occurs by mitogen-activated
      protein kinase pathways without oxidation of cellular glutathione or thioredoxin
      1.
AB  - The gp91phox homologue Nox1 produces H2O2, which induces cell growth,
      transformation, and tumorigenicity. However, it has not been clear whether H2O2
      effects are mediated indirectly via a generally oxidizing cellular environment or
      whether H2O2 more directly targets specific signaling pathways. Here, we
      investigated signaling by H2O2 induced by Nox1 overexpression using a luciferase
      reporter regulated by the antioxidant response element ARE4. Surprisingly, Nox1
      derived H2O2 activated the reporter gene 15-fold with no effect on the redox
      state of the major thiol antioxidant substances, glutathione and thioredoxin.
      H2O2 signaling to ARE4 was mediated by activation of both the c-Jun N-terminal
      kinase and ERK1/2 pathways modulated by Ras. Thus, "redox signaling" resulting in
      kinase signaling pathways is distinct from "oxidative stress," and is mediated by
      discrete, localized redox circuitry.

PMID- 14638696
TI  - Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB
      activation.
AB  - Engagement of the T-cell receptor (TCR) initiates a signaling cascade that
      ultimately results in activation of the transcription factor NF-kappaB, which
      regulates many T-cell functions including proliferation, differentiation and
      cytokine production. Herein we demonstrate that Rip2, a caspase recruitment
      domain (CARD)-containing serine/threonine kinase, plays an important role in this
      cascade and is required for optimal TCR signaling and NF-kappaB activation.
      Following TCR engagement, Rip2 associated with Bcl10, a CARD-containing signaling
      component of the TCR-induced NF-kappaB pathway, and induced its phosphorylation.
      Rip2-deficient mice were defective in TCR-induced NF-kappaB activation,
      interleukin-2 production, and proliferation in vitro and exhibited defective T
      cell-dependent responses in vivo. The defect in Rip2-/- T-cells correlated with a
      lack of TCR-induced Bcl10 phosphorylation. Furthermore, deficiency in Bcl10
      dependent NF-kappaB activation could be rescued in Rip2-/- embryonic fibroblasts
      by exogenous wild-type Rip2 but not a kinase-dead mutant. Together these data
      define an important role for Rip2 in TCR-induced NF-kappaB activation and T-cell
      function and highlight the significance of post-translational modification of
      Bcl10 by Rip2 in T-cell signaling.

PMID- 14638697
TI  - Sarco(endo)plasmic reticulum Ca2+ ATPases (SERCA1 and -2) in human extraocular
      muscles.
AB  - PURPOSE: To investigate the composition of the fibers in human extraocular
      muscles (EOMs) with respect to the sarco(endo)plasmic reticulum Ca(2+)ATPases
      (SERCA)-1 and -2 and to investigate possible correlations between SERCA and
      myosin heavy chain (MyHC) composition. METHODS: EOM samples were processed for
      immunocytochemistry with monoclonal antibodies specific against SERCA1 (fast
      isoform), SERCA2 (slow isoform), or different MyHCs. A total of 1571 fibers were
      analyzed. Microsomal EOM fractions were analyzed with SDS-PAGE and immunoblots.
      RESULTS: The fast fibers, containing MyHCIIa, accounted for 79% of the fibers in
      the orbital layer (OL) and 74% in the global layer (GL). More than 99% of these
      fibers contained SERCA1, and 86% of them coexpressed SERCA1 and -2. Almost all
      slow fibers stained with SERCA2; 54% of those in the GL and all in the OL
      coexpressed SERCA1 and -2. Fifteen percent of the fibers in the GL and less than
      1% in the OL were MyHCeom(pos)/MyHCIIa(neg) fibers. All these contained SERCA1
      and in the OL also stained strongly with anti-SERCA2. Biochemically SERCA2 was
      more abundant than SERCA1. CONCLUSIONS: The human EOMs had a very complex pattern
      of expression of the major protein regulating fiber relaxation rate. The
      coexistence of SERCA1 and -2, together with complex mixtures of MyHCs in most of
      the fibers provide the human EOMs with a unique molecular portfolio that allows a
      highly specific fine-tuning regimen of contraction and relaxation.

PMID- 14638698
TI  - Familial keratoconus with cataract: linkage to the long arm of chromosome 15 and
      exclusion of candidate genes.
AB  - PURPOSE: Keratoconus and cataract are common causes of visual morbidity. Both
      conditions show genetic predisposition. The purpose of this study was to map the
      disease locus in a large three-generation family affected by combined early-onset
      autosomal dominant anterior polar cataract and clinically severe keratoconus.
      Uniquely, in this family both disorders were present and fully penetrant in those
      affected. METHODS: Thirty members of the family were examined clinically on two
      occasions, at an interval of 5 years, to establish their phenotypes and determine
      the progression of the disease. Genomic DNA was extracted from blood samples of
      16 affected and 14 unaffected individuals, and typed with more than 350 highly
      polymorphic microsatellite loci in a genome-wide linkage screen. Markers were
      amplified by PCR with fluorescently labeled primers and sized with an automated
      DNA analyser before calculation of lod scores. After linkage was established,
      several positional candidate genes were assessed by PCR-based DNA sequencing.
      RESULTS: The locus for keratoconus with cataract was mapped to a 6.5-Mb region of
      the long arm of chromosome 15, at 22.33-24.2 between CYP11A and D15S211. The
      positional and functional candidate genes CTSH, CRABP1, IREB2, and RASGRF1 were
      excluded as the cause of keratoconus with cataract in this family. CONCLUSIONS:
      This is the first report of a family with autosomal dominant inheritance of
      keratoconus in association with cataract. The causative gene maps to the long arm
      of chromosome 15 but has not yet been identified.

PMID- 14638699
TI  - Cellular localization of the MPP4 protein in the mammalian retina.
AB  - PURPOSE: Membrane protein, palmitoylated (MPP)-4 is a novel retina-specific
      member of the p55-like subfamily of membrane-associated guanylate kinases
      (MAGUKs). MAGUKs are known to act as scaffolding molecules for multiprotein
      complexes at specialized regions of the plasma membrane. The goal of this study
      was to characterize the MPP4 protein and to determine its location in the
      mammalian retina. METHODS: RT-PCR and 5' and 3' rapid amplification of cDNA ends
      (RACE) techniques were used to isolate and sequence the full-length bovine MPP4
      cDNA. Polyclonal antisera against the bovine MPP4 protein were generated in
      rabbits immunized with synthetic peptides. Affinity-purified anti-MPP4 antibodies
      were used to investigate the properties and distribution of MPP4 in retina and
      transfected 293-Ebna cells by Western blot analysis and immunofluorescence
      microscopy. RESULTS: The full-length bovine MPP4 cDNA encodes a putative bovine
      MPP4 protein of 640 amino acids with a predicted molecular mass of 72.9 kDa.
      Affinity-purified anti-MPP4 antibodies specifically detected the MPP4 protein in
      extracts from retina and 293-Ebna cells transfected with the MPP4 cDNA.
      Immunofluorescence analyses revealed that both the bovine and porcine MPP4
      proteins are localized in the connecting cilia and synaptic terminals of cone and
      rod photoreceptors. In addition, postsynaptic structures in the outer plexiform
      layer and three distinct bands in the inner plexiform layer were MPP4-positive.
      In porcine but not bovine retina, a subclass of cone bipolar cells were labeled
      with anti-MPP4. CONCLUSIONS: The concurrent presence of MPP4 in connecting cilia
      and synaptic structures suggests that MPP4 plays a role at membrane-cytoskeleton
      interfaces in distinct structural and functional compartments of bovine and
      porcine retinas. This work provides the basis for further investigations into the
      function of MPP4 as a retinal scaffolding molecule and its possible role in
      retinal disease.

PMID- 14638700
TI  - Five-year incidence of bilateral cause-specific visual impairment in the
      Melbourne Visual Impairment Project.
AB  - PURPOSE: To describe the age-, gender-, and cause-specific 5-year incidence of
      bilateral visual impairment in participants in the Melbourne Visual Impairment
      Project, Victoria, Australia. METHODS: Participants aged 40 years and older were
      recruited from Melbourne, Victoria, Australia, by random cluster sampling. The
      mean age of the 3271 (83% of the eligible) participants was 59 +/- 12 (SD) years.
      Of the participants, 54% were female. The initial baseline study (1992-1994) was
      followed by a 5-year incidence study (1997-1999). At both time points of the
      study, participants underwent a standardized testing procedure. Distance and near
      vision was tested using logarithm of the minimum angle of resolution (logMAR)
      charts, followed by refraction if needed. Visual fields were assessed by the 24-2
      Humphrey field test (FastPac, Humphrey Field Analyzer; Carl Zeiss Meditec,
      Dublin, CA). Also, intraocular pressure, ocular motility, dilated ophthalmoscopy,
      and photography of the lens and the fundus were conducted. Furthermore, an
      interview included demographic characteristics, history of eye disease, medical
      history, and medication use. For classification of visual impairment, both visual
      acuity (VA) and visual fields (VF) examination results were used. Four levels of
      bilateral presenting visual impairment were defined: mild (VA, <20/40-20/60,
      and/or VF, homonymous hemianopia), moderate (VA, <20/60-20/200, and/or VF,
      constriction <20 degrees to 10 degrees from fixation), severe (VA, <20/200
      10/200, and/or VF, constriction <10 degrees to 5 degrees from fixation), and
      profound (VA, <10/200, and/or VF, constriction <5 degrees from fixation). For all
      participants found to be visually impaired, the major cause was identified.
      RESULTS: Of the 3040 people eligible to attend follow-up 2594 (85%) participated.
      Data were available for 2530 (98%) participants. In 105 participants (4.22%; 95%
      confidence limit 2.58-5.85) some degree of visual impairment developed. The main
      causes were undercorrected refractive error (59%), age-related macular
      degeneration, cataract and neuro-ophthalmic disorders (7% each), glaucoma (3%),
      and diabetic retinopathy (1%). The main cause of severe and profound visual
      impairment was age-related macular degeneration (37%). CONCLUSIONS:
      Undercorrected refractive error was the primary cause of new cases of visual
      impairment in this population. Further research is needed to understand the
      origin of this and to develop appropriate prevention measures. Age-related
      macular degeneration is the primary cause of severe or profound vision loss in
      Australia. This disease requires further investigation for effective cure and
      preventive strategies.

PMID- 14638701
TI  - Inhibition by triptolide of IL-1-induced collagen degradation by corneal
      fibroblasts.
AB  - PURPOSE: Extracts of the herb Tripterygium wilfordii hook f, the major component
      of which is triptolide, have been used in traditional Chinese medicine for the
      treatment of rheumatoid arthritis. Triptolide also exerts many other biological
      actions both in vitro and in vivo. The effect of this agent on collagen
      degradation by cultured corneal fibroblasts was examined. METHODS: Rabbit corneal
      fibroblasts were cultured in three-dimensional gels of type I collagen and in the
      absence or presence of interleukin (IL)-1beta or triptolide. The extent of
      collagen degradation was determined by measurement of the amount of
      hydroxyproline generated by acid-heat hydrolysis of the culture supernatants. The
      activities of matrix metalloproteinase (MMP)-1 and plasmin were measured with the
      specific substrates thiopeptolide and S-2251, respectively. The release of MMPs
      into the culture supernatant was assessed by immunoblot analysis and gelatin
      zymography, and the abundance of MMP mRNAs in the cells was determined by reverse
      transcription and real-time polymerase chain reaction. RESULTS: Triptolide
      inhibited the IL-1beta-induced degradation of collagen by corneal fibroblasts in
      a dose- and time-dependent manner. Neither the activity of purified recombinant
      MMP-1 nor that of plasmin in culture supernatants was affected by triptolide. The
      IL-1beta-induced expression of MMP-1, -2, -3, and -9 by corneal fibroblasts was
      inhibited by triptolide at the protein or mRNA level. CONCLUSIONS: Triptolide
      inhibits collagen degradation by corneal fibroblasts by inducing downregulation
      of the production of MMPs, without directly affecting the collagenolytic activity
      of these enzymes.

PMID- 14638702
TI  - The effects of novel amphipathic block copolymers on stabilization of the rat
      tear film.
AB  - PURPOSE: To determine whether various novel amphipathic polymers could be used to
      stabilize the tear film of the rat. The rheologic properties of these polymers
      were examined to investigate whether particular structural or physical
      characteristics improve the stability of the tear film. METHODS: Amphipathic
      polymers or particular phospholipids were mixed with a test solution of tears and
      saline and applied to the clean, dry corneal surface of a rat. The specular
      reflection of the tear film was observed at high magnification and recorded. For
      each of the polymers or lipids, the effects on surface regularity and tear break
      up time were compared. After the experiments, histologic sections of the tested
      eyes were prepared and examined for acute cytotoxic effects on the cornea and
      ocular conjunctiva. RESULTS: Tear film break-up time was markedly affected by
      differences in polymer structure. Copolymers consisting of separate hydrophobic
      and hydrophilic regions appeared to be the best stabilizers. No acute cytotoxic
      effects were observed in histologic sections of corneas to which the polymers had
      been applied. CONCLUSIONS: Amphipathic polymers can be designed to increase tear
      film stability. Increased tear film stability occurred more readily with
      copolymers, possibly through their interaction with both lipid and aqueous tear
      components.

PMID- 14638703
TI  - UV-induced corneal epithelial cell death by activation of potassium channels.
AB  - PURPOSE: The purpose of the present study is to determine the role of K+ channel
      activity as an early event in UV-induced corneal epithelial cell apoptosis.
      METHOD: Both cell-attached and nystatin-perforated patch-clamping were performed
      to record K+ channel activity in rabbit corneal epithelial (RCE) and primary
      cultured rabbit corneal epithelial (PRCE) cells exposed to UV irradiation. On
      exposure of corneal epithelial cells or intact corneas to UV-C irradiation or
      treatment of corneal epithelial cells with etoposide, cell apoptosis was
      determined by DNA fragmentation, ethidium bromide-acridine orange nuclear stain
      and TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS: In the present study,
      UV-irradiation-induced corneal epithelial cell apoptosis through activation of a
      K+ channel in the cell membrane was an early event in response to UV irradiation.
      UV-C irradiation (42 microJ/cm(2)) activated robust K+ channel activity in RCE
      and PRCE cells at both the single-channel and whole-cell levels, when measured
      with the cell-attached and nystatin-perforated patch clamps, respectively.
      Suppression of UV-irradiation-induced K+ channel activity with the specific K+
      channel blocker 4-aminopurydine (4-AP) prevented UV-irradiation-induced apoptosis
      in the RCE and PRCE cells, loss of the superficial layer of corneal epithelium,
      and apoptosis in the basal layer corneal epithelium. However, suppression of K+
      channel activity did not protect RCE and PRCE cells from etoposide, a
      topoisomerase II inhibitor, which induced cell death by bypassing the membrane.
      Furthermore, application of valinomycin, a K+ ionophore, to mimic the effect of
      mass activation of the K+ channel in RCE and PRCE cells caused cell apoptosis.
      CONCLUSIONS: The results indicate that UV irradiation induces superactivity of K+
      channels in the membrane is an early event mediating signaling transduction and
      resulting in corneal epithelial cell death in response to UV irradiation.

PMID- 14638704
TI  - UV-induced signaling pathways associated with corneal epithelial cell apoptosis.
AB  - PURPOSE: UV-C irradiation of corneal epithelial cells elicits K+ channel
      activation, which in turn causes them to undergo apoptosis. In the present study,
      the intermediary role played by mitogen-activated protein kinase (MAPK) signaling
      pathways in mediating this response was investigated. METHODS: Western blot and
      kinase assays were used to measure UV-induced activation (i.e., phosphorylation)
      of c-Jun NH(2)-terminal kinase (JNK)/SEK, extracellular signal-regulated kinase
      (ERK), and p38. Corneal epithelial apoptosis was determined by measuring caspase
      3 activity. RESULTS: UV-irradiation-induced increases in cell membrane K+ channel
      activity resulted in activations of JNK, SEK upstream of JNK, and caspase 3
      downstream of JNK. Suppression of K+ channel activity with specific K+ channel
      blockers significantly inhibited UV-irradiation-induced activation of JNK
      cascades. However, suppression of K+ channel activity did not prevent
      hyperosmotic-stress-induced JNK activation. In addition, UV-irradiation-induced
      SEK/JNK activation was unaffected by removal of extracellular free Ca2+ with
      EGTA. CONCLUSIONS: UV-irradiation-induced corneal epithelial cell apoptosis is
      mediated through activation of the SEK/JNK signaling pathway. Such activation is
      dependent on increases in K+ channel activity, which play an important role in
      the early events that result in activation of this pathway.

PMID- 14638705
TI  - Cryopreservation of human donor corneas with dextran.
AB  - PURPOSE: To assess freeze-thaw-induced endothelial cell loss by using phase
      contrast microscopy and early morphologic changes within each layer of human
      donor corneas by using confocal microscopy. METHODS: Twenty-eight human corneas
      were cryopreserved in minimum essential medium containing 10% dextran with a
      molecular weight (MW) of 500,000 as an extracellular cryoprotectant, at a cooling
      rate of 1 degrees C/min and stored in liquid nitrogen at -196 degrees C. After
      thawing, the tissue was organ cultured to detect latent cell damage. In 22 of the
      corneas, the endothelial layer was subjected to routine phase-contrast microscopy
      after 24 hours of organ culturing. The other six specimens were evaluated layer
      by layer in a scanning slit confocal microscope after 6, 24, and 48 hours of
      organ culturing. RESULTS: Before cryopreservation, the mean +/- SD numerical
      density of endothelial cells was 1940 +/- 220 cells/mm(2). After cryopreservation
      and subsequent organ culturing, the endothelial cell density decreased to 1300 +/
      360 cells/mm(2), and two of the corneas had a completely necrotic endothelium (P
      = 0.001). Confocal microscopy revealed all corneal layers in each of the six
      specimens examined to be structurally integral after 48 hours of organ culturing.
      Although the reflectivity of some of the keratocytes was enhanced, there were no
      signs of keratolysis. CONCLUSIONS: The present study demonstrates that each
      corneal layer is capable of regaining its structural integrity after
      cryopreservation in the presence of dextran. Because the freeze-thaw-induced
      endothelial cell loss is still highly variable, the technique must be further
      refined before it can be applied clinically.

PMID- 14638706
TI  - Differences in clinical parameters and tear film of tolerant and intolerant
      contact lens wearers.
AB  - PURPOSE: To determine whether intolerance to contact lens wear is attributable to
      clinical or protein characteristics of the tear film. METHODS: Thirty-eight
      subjects participated; 20 were successful contact lens wearers and 18 had
      discontinued contact lens wear because of discomfort. Baseline tear film (no lens
      wear) was analyzed with a range of clinical measurements and protein analyses
      (lactoferrin, sIgA, and lysozyme). Comfort was determined after 6 hours of lens
      wear, and differences in tear film characteristics between subject groups were
      determined. In half of the subject group (n = 19), discriminant analysis was used
      to develop an equation for predicting the likelihood of intolerance to lens wear.
      Sensitivity and specificity were determined by testing the formula on the
      remaining subjects. These formulas were also tested on a separate group of
      subjects enrolled in a contact lens-wearing trial. RESULTS: Tear volume (meniscus
      height and phenol red thread test) and tear stability (noninvasive tear break up
      time [NI-TBUT]) were significantly reduced in intolerant wearers (P < 0.05). A
      greater number of symptoms were reported by intolerant than by tolerant wearers
      (P < 0.05). Tolerance was associated with clinical but not protein
      characteristics of the tear film. Formulas best able to predict contact lens
      intolerance included NI-TBUT, number of symptoms experienced, and tear film
      meniscus height. Formulas had high sensitivity, and specificity which ranged from
      29% to 57%. CONCLUSIONS: Contact lens intolerance appears to be best predicted by
      a combination of clinical variables, including tear film stability, tear volume,
      and symptom reporting.

PMID- 14638707
TI  - Different cell sizes in human limbal and central corneal basal epithelia measured
      by confocal microscopy and flow cytometry.
AB  - PURPOSE: In the epidermis, the highest clonogenicity, a feature of stem cells
      (SCs), is found in the smallest keratinocyte. In the limbal-corneal (LC)
      epithelium the SCs are exclusively localized in the basal epithelial layer of the
      limbal domain. The current study was conducted to determine whether this spatial
      SC arrangement is reflected in differences in the cell size between limbal and
      corneal cells. METHODS: In vivo confocal microscopy was used to scan and measure
      the size of the cells of the central cornea and the superior limbus in five
      normal subjects, from the superficial to the basal cell layer. Limbal and corneal
      pure epithelial sheets were isolated by dispase digestion from human tissues and
      dissociated into single cells by trypsin digestion. The forward (FSC; a relative
      measure of cell size) and side (SSC; a relative measure of cytoplasmic
      complexity) light-scattering properties of these cells were determined by flow
      cytometry. RESULTS: Confocal microscopy showed that diameters of the basal cells
      of the limbal and corneal zones were 10.1 +/- 0.8 and 17.1 +/- 0.8 micro m,
      respectively. The corresponding values for the superficial layers were 19.9 +/-
      1.6 and 36.6 +/- 1.6 microm, respectively (P < 0.0001). The mean FSC and SSC of
      the limbal cells amounted to 65.7% +/- 8.7% and of the corneal cells, 74.4% +/-
      4.6%. Furthermore, only 1.40% +/- 0.83% and 0.69% +/- 0.37% of the corneal cells
      had FSC and SSC equal to the lowest 15% of FSC and SCC of the limbal cells,
      respectively, indicating that the limbus contained a substantial proportion of
      very low FSC and SSC cells for which there was no corneal counterpart.
      CONCLUSIONS: The data collectively demonstrate that the smallest cells are
      located in the limbal basal epithelium. This feature may help isolate corneal SCs
      located in the limbus.

PMID- 14638708
TI  - Stromal niche controls the plasticity of limbal and corneal epithelial
      differentiation in a rabbit model of recombined tissue.
AB  - PURPOSE: The adult rabbit limbal basal epithelium contains corneal epithelial
      stem cells, which have been characterized by a negative expression of keratin-3
      (K3) and a lower expression of connexin 43 (Cx43). This study was conducted to
      determine whether the limbal stroma dictates the plasticity of limbal and corneal
      epithelial differentiation. METHODS: Viable epithelial sheets of the central
      cornea and the pigmented limbus were isolated from Dutch belted rabbits by
      incubation of 50 mg/mL of dispase II in supplemental hormonal epithelial medium
      (SHEM) for 18 hours at 4 degrees C. The cleavage plane was studied by
      immunostaining with antibodies against K3, Cx43, integrin beta1, and collagen IV.
      Viability of single cells derived from these sheets was assessed by a live-dead
      assay. Such limbal (L) and corneal (K) epithelial sheets were recombined with
      either limbal (Ls) or corneal (Ks) stroma, and cultured in SHEM for 10 days
      before lifting to the air-fluid interface for 1 week. The resultant epithelial
      phenotype was determined by histology and immunostaining to K3 and Cx43, and
      apoptosis was investigated by Hoechst and TUNEL nuclear staining. RESULTS:
      Viability of isolated limbal and corneal epithelial sheets was determined to be
      91.1% +/- 2.9%. The basal epithelium of isolated limbal epithelial sheets was
      positive for integrin beta1, negative for K3, but weakly positive for Cx43, and
      still retained patches of collagen IV. All recombinants showed stratified
      epithelia, with intraepithelial cysts with desquamated debris noted only in K/Ks,
      and epithelial outgrowth onto the insert filter from L/Ls. As expected,
      expression of K3 was negative in the basal layer of L/Ls, but positive in that of
      K/Ks. Expression of K3 was sporadically positive in the basal layer of L/Ks but
      largely negative in that of K/Ls. Expression of Cx43 was uniformly expressed in
      the basal layer of the K/Ks, but weak in that of L/Ls, K/Ls, and L/Ks. A higher
      apoptosis index was only noted in intraepithelial cysts of K/Ks. CONCLUSIONS:
      These results strongly indicate that the limbal stroma modulates epithelial
      differentiation, proliferation and apoptosis in the direction favoring stemness,
      whereas the corneal stroma promotes differentiation. Further investigation into
      elements constituting such a niche should help unveil the secrecy whereby
      stemness is controlled.

PMID- 14638709
TI  - Human keratocytes cultured on amniotic membrane stroma preserve morphology and
      express keratocan.
AB  - PURPOSE: To develop a new method of expanding human corneal keratocytes in serum
      while maintaining their characteristic morphology and keratocan expression.
      METHODS: Human keratocytes were isolated from central corneal buttons by
      digestion in 1 mg/mL of collagenase A in DMEM and seeded on plastic or the
      stromal matrix of human amniotic membrane (AM) in DMEM with different
      concentrations of FBS. On confluence, cells on AM were continuously subcultured
      for six passages on AM or plastic. In parallel, cells cultured on plastic at
      passages 3 and 11 were reseeded on AM. Cellular morphology and cell-cell networks
      were assessed by phase-contrast microscopy and a cell viability assay,
      respectively. Expression of keratocan was determined by RT-PCR and Western blot
      analysis. RESULTS: Trephined stroma yielded 91,600 +/- 26,300 cells (ranging from
      67,000 to 128,000 cells per corneal button). Twenty-four hours after seeding,
      cells appeared dendritic on AM, even in 10% FBS but fibroblastic on plastic. Such
      a difference in morphology correlated with expression of keratocan assessed by RT
      PCR and Western blot, which was high and continued at least to passage 6 on AM,
      even in 10% FBS, but was rapidly lost each time when cells on AM were passaged on
      plastic. Fibroblasts continuously cultured on plastic to passages 3 and 11 did
      not reverse their morphology or synthesize keratocan when reseeded on plastic in
      1% FBS or on AM. CONCLUSIONS: Human keratocytes maintain their characteristic
      morphology and keratocan expression when subcultured on AM stromal matrix even in
      the presence of high serum concentrations. This method can be used to engineer a
      new corneal stroma.

PMID- 14638710
TI  - Optokinetic nystagmus in strabismus: are asymmetries related to binocularity?
AB  - PURPOSE: Strabismus may be associated with an asymmetry of monocular horizontal
      optokinetic nystagmus (OKN). It is unclear whether OKN asymmetries are associated
      with deficiency in binocular and/or stereovision. In the current study, patients
      with different degrees of binocularity were investigated. METHODS: OKN was
      examined in the dominant and nondominant eyes of four groups of patients: (1) no
      measurable binocularity (NB), (2) poor binocularity (PB)-that is, showing
      binocularity on the Bagolini Test and/or rudimentary stereovision, (3) good
      binocularity (GB) with good stereoacuity after squint surgery, and (4) a control
      group. Monocular OKN was elicited with black-and-white stripes moving temporally
      to nasally (TN) or nasally to temporally (NT) at velocities of 15, 30, 45, and 60
      deg/s. Eye movements were recorded with infrared oculography. RESULTS: Only
      subjects in the NB group showed a significant OKN asymmetry, with preference for
      TN stimulation in dominant and nondominant eyes. Subjects with PB did not have
      significant OKN asymmetries but reduced OKN gains in both stimulus directions.
      Subjects with GB had normal mean OKN gains without asymmetry. Larger OKN
      asymmetries were correlated with younger age at detection of strabismus if NB and
      GB were grouped together, but not if each group was analyzed separately.
      CONCLUSIONS: For the first time, a large groups of patients classified by level
      of binocular vision has been investigated. The results show that OKN gain and
      asymmetry are associated with the development of binocular vision. OKN
      investigation may be helpful to identify patients with binocularity or binocular
      potential in strabismus.

PMID- 14638711
TI  - Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia
      glaucomatous mice: comparison with RGC loss in aging C57/BL6 mice.
AB  - PURPOSE: To quantify the extent and pattern of retinal ganglion cell (RGC) loss
      in the DBA2/NNia glaucomatous mouse strain as a function of age and compare it
      with ganglion cell loss in a nonglaucomatous strain. METHODS: All the ganglion
      cells in retinas of DBA/2NNia and C57/BL6 mice of various ages (five eyes per age
      group in 3-month intervals from 3 to 18 months of age) were counted. A novel
      counting method that does not rely on sampling and that uses retrograde labeling
      of RGCs with Fluorogold (Fluorochrome; Englewood, CO) was used. RGC loss in the
      glaucomatous DBA/2NNia mouse strain was contrasted to RGC loss in C57 mice at the
      same ages. The total number of Fluorogold-labeled cells per retina was compared
      within and among the two strains as a function of age. In addition, RGC density
      maps were constructed for each retina, and the range of densities for each age
      group was compared within and among the two strains. IOP in awake, nonsedated
      DBA/2NNia mice was measured with a rebound tonometer. RESULTS: RGC loss started
      between 12 and 15 months of age in C57 mice and led to an approximate 46%
      reduction by 18 months of age. The rate of loss was best approximated by a second
      order polynomial curve. In comparison, DBA/2NNia mice also began showing RGC loss
      at approximately 12 months of age, but it proceeded at a much faster rate, with
      approximately 64% of their RGCs dying by the 15th month of age but little
      additional loss thereafter. RGC loss in the DBA animals had a focal pattern that
      appeared more patchy and showed greater variability than the age-related loss in
      C57 mice, which was more diffuse. IOP and total retinal area in DBA/2NNia mice
      began to increase at approximately 6 months of age. IOP normalized after the 12th
      month of age. CONCLUSIONS: Age-related RGC loss of up to 50% can occur in the C57
      mouse by 18 months of age. The loss does not proceed linearly with age, as is
      often assumed, and differs both in extent and locational pattern from pathologic
      RGC loss secondary to glaucoma in DBA/2NNia mouse retinas.

PMID- 14638712
TI  - Altered peripheral sensitivity to glucocorticoids in primary open-angle glaucoma.
AB  - PURPOSE: Increased levels of glucocorticoids are associated with raised
      intraocular pressure (IOP). The activity of glucocorticoids is regulated at a
      prereceptor level by 11beta-hydroxysteroid dehydrogenases (11beta-HSD). This
      study was an investigation of the central and peripheral sensitivity to
      glucocorticoids in patients with POAG or ocular hypertension (OHT) and the
      differential metabolism of glucocorticoids by 11beta-HSDs. METHODS: Patients with
      POAG or OHT and normal control subjects were studied. Peripheral sensitivity to
      glucocorticoids was assessed as dermal blanching and central sensitivity by
      dexamethasone suppression testing. Daily production rates of glucocorticoids were
      determined by quantifying metabolites in 24-hour urine. Plasma cortisol levels
      were determined at baseline (9 AM) and after an overnight low-dose dexamethasone
      suppression test. In a separate study, plasma and aqueous humor cortisol levels
      were determined in patients with POAG and normal subjects. RESULTS: Patients with
      POAG exhibited a greater cutaneous vasoconstrictor response to glucocorticoids
      than patients with OHT and normal subjects (20.7 +/- 3.1 vs. 8.5 +/- 4.4 and 8.6
      +/- 4.5 arbitrary units, respectively; P < 0.05 in each case). Total
      glucocorticoid production rates were not different between groups, nor were total
      circulating cortisol levels before or after suppression of the hypothalamic
      pituitary-adrenal axis by dexamethasone or concentrations in aqueous humor. The
      ratio of urinary cortisol to cortisone metabolites was elevated in POAG versus
      normal control and OHT (1.74 +/- 0.13 vs. 1.34 +/- 0.11 and 1.32 +/- 0.14; P <
      0.05 in each case), indicating a change in the balance of 11beta-HSDs, without a
      change in other metabolic pathways. CONCLUSIONS: Patients with POAG exhibit
      increased peripheral vascular sensitivity to glucocorticoids. Increased
      sensitivity of glucocorticoid receptors, may enhance local glucocorticoid action
      in the eye and exacerbate the adverse effects of glucocorticoids in this
      condition.

PMID- 14638713
TI  - Aqueous humor dynamics in mice.
AB  - PURPOSE: To assess aqueous humor dynamics in mouse eyes. METHODS: Aqueous humor
      dynamics of NIH Swiss White mouse were assessed with an injection and aspiration
      system, using fine glass microneedles. Intraocular pressure (IOP) was measured by
      a microneedle connected to a pressure transducer. Episcleral venous pressure
      (EVP) was measured by gradually lowering intracameral pressure until blood reflux
      into Schlemm's canal was observed. Outflow facility (C) was determined based on
      constant pressure perfusion measurements obtained at two different IOPs. Aqueous
      volume (V(a)) was determined by direct measurement of aspirated aqueous humor.
      Aqueous humor production (F(a)) was measured by the dilution method with
      rhodamine-dextran. Conventional and uveoscleral outflow (F(c) and F(u),
      respectively), as well as the turnover rate of aqueous humor, were also
      calculated. RESULTS: IOP and EVP were 15.7 +/- 2.0 and 9.5 +/- 1.2 mm Hg,
      respectively (n = 20). F(a) was 0.18 +/- 0.05 microL/min (mean +/- SD; n = 8). C
      was 0.0051 +/- 0.0006 microL/min per mm Hg (n = 8). Estimated F(c) and F(u) were
      0.032 and 0.148 microL/min, respectively. F(c) was 18% of F(a). F(u) was 82% of
      F(a). V(a) was 5.9 +/- 0.5 microL (n = 8). The calculated turnover rate of
      aqueous humor was 2.5%. CONCLUSIONS: The mouse eye has similar aqueous production
      and aqueous humor turnover rate as the human eye. The presence of both
      conventional and uveoscleral outflow suggests that the mouse is a useful model
      system for further investigations of the biology of aqueous dynamics.

PMID- 14638714
TI  - Signaling pathways used in trabecular matrix metalloproteinase response to
      mechanical stretch.
AB  - PURPOSE: Trabecular meshwork (TM) matrix metalloproteinase (MMP), and tissue
      inhibitor (TIMP) changes in response to mechanical stretching appear to be
      central to intraocular pressure (IOP) homeostasis. Studies were conducted to
      define the signal transduction pathway responsible for the increases in MMP-2 and
      -14 that occur in response to mechanical stretching of TM cells. METHODS: Porcine
      TM cells were subjected to mechanical stretching, and changes in MMP-2 and -14
      levels were determined by gelatin zymography and Western immunoblot analysis.
      Effects of signal transduction pathway inhibitors on MMP levels were analyzed.
      Phosphospecific antibodies were used to identify phosphorylation changes in
      select pathway intermediates. In silico secondary structure analysis was
      conducted on the 5' untranslated regions (UTRs) of MMP-2 and -14 mRNAs. RESULTS:
      The increases in MMP-2 and -14 that occur 24 hours after sustained mechanical
      stretching of TM cells were blocked by rapamycin. Wortmannin blocked the MMP-2
      but not the MMP-14 increase. Protein kinase B (PKB) phosphorylation on S473 and
      T308 was increased significantly by stretching. Rapamycin-sensitive
      phosphorylation of T389 in p70/p85 S6 kinase was also increased. The
      phosphorylations of the translation initiation factor eIF-4E on S209 and of its
      inhibitory binding protein 4E-BP1 on T70 were both increased by stretch. The
      calculated free energies of secondary structures of the 5' UTRs of the mRNAs for
      MMP-2 and -14 were negative and relatively large. MMP-2 also had pyrimidine
      tracts in the extreme 5' region of its UTR. CONCLUSIONS: The increases in TM MMP
      2 and -14 protein levels in response to mechanical stretching appear to be
      transduced at least in part by mTOR, the mammalian target of rapamycin (mTOR).
      The wortmannin sensitivity implicates phosphoinositide 3-kinase as a modulator of
      the MMP-2 but not the MMP-14 increase. Integrin-linked kinase (ILK),
      phosphoinositide-dependent kinase (PDK-1), and PKB are implicated in the MMP-2
      increase. Translational initiation involving eIF-4E and its inhibitory binding
      protein 4E-BP1 appear to be involved in both the MMP-2 and -14 increases with
      stretching and are normally regulated by mTOR. The high degree of secondary
      structure in the 5' UTRs of these transcripts is typically an indicator of genes
      specifically sensitive to regulation through this pathway. P70/p85 S6 kinase is
      probably involved downstream from mTOR and PKB in regulating translation of MMP
      2, which has pyrimidine tracts in its 5' UTR. Manipulation of these transduction
      pathways may provide new approaches to therapeutic IOP regulation.

PMID- 14638715
TI  - Latanoprost stimulates secretion of matrix metalloproteinases in tenon
      fibroblasts both in vitro and in vivo.
AB  - PURPOSE: To investigate the presence and the possible role of different matrix
      metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in Tenon capsule
      fibroblasts. These enzymes are essential for the control of tissue remodeling in
      the context of wound repair. This aspect is important to further the
      understanding of and possibly to influence the scarring process of filtering
      blebs after glaucoma surgery. METHODS: Untreated and latanoprost-treated human
      Tenon fibroblasts were examined for the presence of MMPs and TIMPs on the mRNA
      and protein levels. Assays performed included RT-PCR, real-time RT-PCR,
      immunocytochemistry, Western blot analysis, flow cytometry, and zymography. To
      investigate the changes in vivo, conjunctival specimens of rabbits treated with
      latanoprost eye drops were examined by immunohistochemistry. RESULTS: In all
      assays, both MMP-3 and TIMP-2 were detected. With the real-time RT-PCR technique,
      MMP-1, -2, -3, -7, -9, and -14 and TIMP-1 and -2 were detected. An upregulation
      of MMP-3 and TIMP-2 after latanoprost treatment of the fibroblasts was shown and
      found to occur on the mRNA and the protein levels. The upregulation of MMP-3 and
      TIMP-2 was confirmed in vivo. CONCLUSIONS: Tenon fibroblasts contain the ability
      on the mRNA level to synthesize all enzymes of the MMP and TIMP family that are
      related to remodeling of the extracellular matrix. The levels of MMP-3 and TIMP-2
      increase after treatment with latanoprost. Tenon fibroblasts may be the target
      cells for attempts to influence the tissue levels of MMPs and TIMPs in the
      context of conjunctival wound healing after glaucoma surgery.

PMID- 14638716
TI  - Anatomic relationship between lamina cribrosa, intraocular space, and
      cerebrospinal fluid space.
AB  - PURPOSE: The lamina cribrosa, as the main structural element of the optic nerve
      head, forms a pressure barrier between the intraocular space and the retrobulbar
      space. The function as a pressure barrier may have importance for the
      pathogenesis of ocular diseases related to intraocular pressure and/or
      cerebrospinal fluid (CSF) pressure, such as the glaucomas. The purpose of the
      present study was to examine the anatomic relationship between the lamina
      cribrosa, the intraocular pressure space, and the retrobulbar cerebrospinal
      pressure space in eyes with glaucoma. METHODS: The study included 53 globes
      enucleated because of malignant choroidal melanoma (n = 42) without involvement
      of the optic nerve (control group) or because of painful absolute secondary angle
      closure glaucoma (n = 11; glaucoma group). Anterior-posterior histologic sections
      through the pupil and the optic disc were morphometrically evaluated. RESULTS: In
      the glaucoma group compared with the control group, the lamina cribrosa was
      significantly (P < 0.001) thinner, the part of the outer lamina cribrosa surface
      directly exposed to the pia mater and indirectly exposed to the CSF space was
      significantly (P = 0.001) wider, and the shortest distance between the
      intraocular space and the CSF space was significantly (P < 0.001) shorter. The
      posterior lamina cribrosa surface in direct contact with the pia mater was
      located close to the optic disc border. CONCLUSIONS: The thickness of the lamina
      cribrosa and the anatomic relationships between the intraocular space and the CSF
      space differ significantly between normal and glaucomatous eyes. The findings may
      be of importance for the pathogenesis of glaucomatous optic neuropathy.

PMID- 14638717
TI  - Retinal ganglion cells resistant to advanced glaucoma: a postmortem study of
      human retinas with the carbocyanine dye DiI.
AB  - PURPOSE: The present study was conducted to examine whether the morphology of the
      retinal ganglion cells is altered in advanced glaucoma. Perikaryal, axonal, and
      dendritic alterations were monitored in glaucoma-resistant retinal ganglion cells
      by postvitam application of the fluorescent dye DiI. METHODS: The retinas of four
      amaurotic glaucomatous eyes and four normal eyes enucleated after death were used
      in this study. The retinas were freed from surrounding tissue, prepared as
      flatmounts on a nitrocellulose filter, and fixed overnight in 4%
      paraformaldehyde. The retinal ganglion cells were labeled by introducing crystals
      of the fluorescent carbocyanine dye DiI, into the optic fiber layer. This dye
      diffuses along membranes of ganglion cell axons, completely labeling them and
      their cell bodies and dendrites. Further characterization of the retinas and
      optic nerves included hematoxylin-eosin and van Gieson histochemical staining as
      well as immunohistochemistry against glial fibrillary acidic protein. RESULTS:
      Because of the advanced stage of the disease, the retinas were almost completely
      depleted of ganglion cells, which had degenerated and therefore could not be
      stained. The few remaining ganglion cells were considered to be resistant to
      glaucoma. They showed drastic morphologic alterations, such as abnormal axonal
      beading, the cell bodies were normal in size but had irregular silhouettes or
      swellings, and there were fewer dendritic bifurcations. The size of the dendritic
      trees was smaller, implicating pruning of smaller dendritic branches. Glial cells
      were also detected immunocytochemically indicating their involvement in the
      pathologic course of glaucoma. CONCLUSIONS: The data suggest that the few
      ganglion cells that survive the elevated intraocular pressure associated with
      loss of visual function display morphologic changes that are manifested both on
      the cell body and on their intraretinal processes, including axons and dendrites.

PMID- 14638718
TI  - Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of
      retinal ganglion cells in response to stress.
AB  - PURPOSE: Interleukin (IL)-10 has recently been shown to promote survival of
      neurons and glia. The purpose of this report is to investigate whether IL-10 has
      any role in protecting retinal ganglion cells (RGCs) from death under conditions
      in which growth factors are removed, or in which oxidative stress is present.
      Signal transduction pathways that activate IL-10 signaling in RGCs were studied
      in both stress conditions. METHODS: Effects of various interleukins on the
      viability of the RGC cell line was determined, and apoptotic cells were
      quantified. Immunoblot analysis was preformed to identify the IL-10 receptor (IL
      10R) and phosphorylated or nonphosphorylated Akt and STAT-3 proteins in RGC
      extracts. Immunohistochemistry was performed on the rat retinal sections to
      identify native IL-10R. RESULTS: Apoptosis of RGCs in the absence of growth
      factors with or without dexamethasone (1 microM) occurred in 68.5% +/- 3.4% and
      53.4% +/- 2.6% of cells, respectively, after 96 hours. Addition of IL-10 at a
      concentration of 50 ng/mL significantly reduced the apoptotic population of RGCs
      to 28.2% +/- 2.3% in the absence of growth factors with dexamethasone and to 31%
      +/- 2.7% in the absence of growth factors alone. RGCs as well as native retina
      expressed functional IL-10R as determined by immunoblot analysis and by the
      ability of IL-10 to phosphorylate Stat-3. However, IL-10 failed to phosphorylate
      Akt in these cells. CONCLUSIONS: IL-10 caused a 59% and 42% reduction in the
      apoptotic population of serum-deprived cells with and without dexamethasone
      treatment, respectively. These observations establish that activation of IL-10R
      promotes survival of RGCs and this survival-promoting activity is due to IL-10
      signaling through the Stat-3 pathway, which inhibits the cell death and not
      through the Akt cell survival pathway.

PMID- 14638719
TI  - Local retention of soluble antigen by potential antigen-presenting cells in the
      anterior segment of the eye.
AB  - PURPOSE: To determine the capacity of bone marrow-derived cells in the anterior
      segment of the eye to capture a fluorescence-labeled antigen (Ag) injected into
      the anterior chamber (AC). METHODS: Uveal tract and corneoscleral tissues from
      Lewis rats were cultured in vitro, with or without FITC-dextran (4 microg/mL
      final concentration), for 48 hours and examined by confocal microscopy. To
      investigate antigen uptake in vivo 2 microL (20 microg) of Cascade Blue-labeled
      dextran (CB-Dx) was injected into the right AC of Lewis rats. The density of Ag
      positive cells in the iris at 1, 3, 5, or 12 days after injection was examined by
      in vivo video fluorescence microscopy. The distribution and phenotype of Ag
      positive cells in frozen and paraffin-embedded sections of ocular tissues and in
      iris wholemounts from animals killed at 24 hours and day 7 were analyzed by
      fluorescence and confocal microscopy. RESULTS: In organ culture conditions
      numerous cells in the iris, ciliary body, choroid, and corneal limbus were
      capable of capturing fluorescence-labeled Ag. In vivo observations and
      microscopic examination of experimental eyes at days 1 and 7 after AC injection
      revealed Ag-positive cells within the iris, iridocorneal angle, the
      suprachoroidal space and around limbal-episcleral vessels. Ag-bearing cells in
      the iris express combinations of macrophage markers but rarely expressed major
      histocompatibility complex (MHC) class II molecules. A reduced number of Ag
      bearing cells were still present in the iris at day 12. CONCLUSIONS: Potential
      antigen-presenting cells (APCs) in the iris and ciliary body are capable of
      internalizing intracameral Ag. The characteristics of these cells in the iris are
      consistent with a predominantly macrophage phenotype. These observations also
      suggest that the Ag leaving the eye through both the conventional and
      nonconventional aqueous outflow pathways may be captured by potential APCs in the
      episcleral tissues.

PMID- 14638720
TI  - Role of Pseudomonas aeruginosa ExsA in penetration through corneal epithelium in
      a novel in vivo model.
AB  - PURPOSE: The scarified cornea keratitis model was modified to study Pseudomonas
      aeruginosa infection of healing corneal epithelium. The new model was then used
      to study the role of ExsA, a transcriptional activator of P. aeruginosa, in
      bacterial penetration through injured and healing corneal epithelia. METHODS:
      Scratch-injured corneas of C57BL/6 mice were allowed to heal for 0, 6, 9, or 12
      hours before inoculation with a cytotoxic (6206) or invasive (PAO1) P. aeruginosa
      strain. Disease progression was monitored for 14 days. The integrity of the
      healing epithelium was studied in uninfected eyes by fluorescein staining and by
      histologic examination. In other experiments, the effect of bacterial exsA
      mutation was studied after 0, 6, or 12 hours of healing. Three hours after
      infection, these eyes were used to quantify early bacterial colonization levels
      by viable counts, or they were sectioned to study bacterial penetration through
      the epithelium by microscopy. RESULTS: Corneas remained susceptible to infection
      6 but not 12 hours after scratch injury. By 6 hours, the previously exposed
      stroma was already completely covered by several layers of epithelial cells.
      Fluorescein staining unexpectedly occurred even after 12 hours of healing time,
      showing that resistance to infection preceded full restoration of epithelial
      barrier function. Mutation of exsA reduced both bacterial colonization levels and
      penetration through the epithelium 3 hours after bacterial inoculation, but only
      in the 6-hour healing situation, and only for the cytotoxic strain (PA103).
      Mutation of exsA in the invasive strain (PAO1) had no effect on 3-hour
      colonization or penetration levels under any circumstances. CONCLUSIONS: The 6
      hour healing infection model showed a role for ExsA in early interactions with
      the corneal epithelium that was not detectable with the conventional (0-hour)
      scratch model. Comparison of the 6- and 12-hour healing models, which showed that
      factors additional to barrier function contribute to defense against infection,
      could be used to gain new insights into corneal defense mechanisms, and the
      methods used by bacteria to circumvent them.

PMID- 14638721
TI  - Topical treatment with antisense oligonucleotides targeting tumor necrosis factor
      alpha in herpetic stromal keratitis.
AB  - PURPOSE: Tumor necrosis factor (TNF)-alpha is a pleiotropic factor that is
      critical for the development of inflammation. The authors investigated whether
      topical application of TNF-alpha-antagonizing molecules, antisense
      oligonucleotides (ASON), might be an effective way of modifying the course of
      immune-mediated herpetic stromal keratitis (HSK). METHODS: ASON targeting TNF
      alpha mRNA were examined for their efficiency in interfering with the production
      of this cytokine in vitro. In vivo uptake was determined by FITC-labeled ASON.
      HSV-1 corneally infected mice were injected three times with ASON. Mice from the
      control groups received unrelated control oligonucleotides (CON) or buffer. The
      clinical course of HSK, the delayed-type hypersensitivity (DTH) reaction, the
      uptake of [(3)H]thymidine from cells derived from the spleen, virus-neutralizing
      antibody titers in the serum, and viral replication in the infected eyes were
      determined. The eyes were examined histologically. The corneal TNF-alpha content
      was measured by ELISA. RESULTS: The TNF-alpha ASON reduced the lymphocytic
      cytokine expression in vitro. In vivo, the FITC-labeled molecules were detected
      in the cornea even after 10 days. In the TNF-alpha ASON mice the incidence of HSK
      decreased, and the severity of the disease was diminished. The corneal content of
      TNF-alpha was reduced, and the number of inflammatory cells was decreased. The
      other investigated parameters were not significantly altered by TNF-alpha ASON
      treatment. CONCLUSIONS: The data suggest that TNF-alpha ASON diminishes the
      release of TNF-alpha from cultured lymphocytes and from lymphocytes in the HSV-1
      infected cornea. This topical treatment mitigates the course of HSK, whereas the
      systemic antiviral effector functions were not impaired.

PMID- 14638722
TI  - Characterization of vitreous B-cell infiltrates in patients with primary ocular
      lymphoma, using CDR3 size polymorphism analysis of antibody transcripts.
AB  - PURPOSE: Histopathology usually cannot be performed and cytology is unfortunately
      frequently insufficient to confirm a suspicion of primary intraocular lymphoma
      (PIOL). The purpose of this study was to evaluate the Immunoscope technique for
      the identification of ocular B-cell monoclonal infiltrates in patients with
      malignant or immune conditions. METHODS: Polymorphism analysis of the size of the
      third complementarity-determining region (CDR3) of heavy chain antibody
      transcripts was used to differentiate between a polyclonal infiltrate and a
      monoclonal infiltrate within a clinical vitreous sample of two groups of
      patients. PIOL was confirmed in all patients of the first group (n = 6). Five
      patients with autoimmune uveitis or immune-recovery uveitis associated with AIDS
      were included in the control group. The level of IL-10 in the vitreous was
      determined in all patients. RESULTS: In five cases of severe PIOL, CDR3
      polymorphism analysis confirmed the presence of a dominant B-cell clone within
      the eye. In one case of confirmed PIOL presenting with mild vitritis, CDR3
      polymorphism analysis was consistent with the existence of a polyclonal profile
      in the ocular sample studied. Conversely, it was shown that the detection of an
      intraocular monoclonal B-cell population does not necessarily imply ocular
      lymphoma. A clonal expansion was detected in a control patient who exhibited
      merely a nonmalignant response associated with immune-recovery uveitis.
      CONCLUSIONS: This PCR-based technique can make an important contribution to the
      characterization of intraocular B cells, but it alone cannot confirm or exclude
      the existence of a malignant lymphocyte proliferation. In the evaluation of a
      patient with intraocular inflammation in whom PIOL is suspected, CDR3
      polymorphism analysis is recommended to confirm clonality. In general, the
      information about lymphocyte diversity provided by this technology opens up new
      possibilities for the analysis of ocular infiltrates.

PMID- 14638723
TI  - Splenic B cells act as antigen presenting cells for the induction of anterior
      chamber-associated immune deviation.
AB  - PURPOSE: To characterize the role of B cells in the induction of anterior chamber
      associated immune deviation (ACAID). METHODS: An in vitro model of the ACAID
      spleen was used to recapitulate the events that occur when antigen is introduced
      into the anterior chamber of the eye and culminates in the appearance of antigen
      specific, CD8(+) suppressor cells. RESULTS: In vitro-generated suppressor cells
      mimicked those produced by anterior chamber injection of antigen, as shown by
      their antigen specificity, surface expression of CD8, and capacity to suppress
      DTH, which is mediated by previously immunized T cells. B cells were found to be
      necessary for suppressor cell development. The B cell receptor (BCR) was
      necessary for the induction of ACAID and conveyed antigen specificity to the
      suppressor T cells. Lysosomal acidification of internalized antigen was necessary
      for B cells to induce ACAID; however, transporter of antigen processing (TAP) was
      not required for the generation of ACAID. CONCLUSIONS: The results suggest that B
      cells use the BCR to capture and internalize antigen from ACAID-inducing
      macrophages. Lysosomal acidification of the captured antigen is essential for the
      processing of the ACAID antigen before TAP-independent presentation to suppressor
      cells.

PMID- 14638724
TI  - Targeted deletion of the lens fiber cell-specific intermediate filament protein
      filensin.
AB  - PURPOSE: To determine the function of the lens fiber cell-specific cytoskeletal
      protein, filensin, in lens biology. METHODS: Targeted genomic deletion was used
      to delete exon 1 and the transcriptional start site of the filensin gene.
      Resultant chimeric animals were bred to homozygosity for the mutant allele. These
      animals were outbred to mice bearing the wild-type CP49 alleles to eliminate the
      mutant CP49 gene carried by the 129 strain of mice. Animals homozygous for the
      mutated filensin gene and wild-type CP49 gene were compared with wild-type and
      heterozygous animals by Northern and Western blot analyses, light and electron
      microscopy, and slit lamp microscopy. RESULTS: Disruption of the filensin gene
      successfully blocked production of filensin mRNA, reduced levels of filensin's
      assembly partner CP49, and prevented the assembly of beaded filaments. Despite
      the absence of beaded filaments, lenses did not show obvious changes in fetal
      development, nor in the differentiation of epithelial cells into mature fiber
      cells, as judged by light microscopic analysis. Filensin knockouts began to show
      evidence of light-scattering by 2 months and worsened with age. Heterozygous
      animals exhibited an intermediate phenotype, showing a reduction in filensin
      transcript and moderate light-scattering at 5 months. CONCLUSIONS: The lens fiber
      cell-specific intermediate filament protein filensin is essential for beaded
      filament assembly. However, although beaded filaments are not needed for normal
      lens fetal development or fiber cell differentiation, they appear to be necessary
      for the long-term maintenance of optical clarity. The mechanism by which the
      absence of filensin and the beaded filament affects optical clarity has yet to be
      defined.

PMID- 14638725
TI  - Protein kinase Cgamma regulation of gap junction activity through caveolin-1
      containing lipid rafts.
AB  - PURPOSE: To demonstrate the interactions of PKCgamma with caveolin (Cav)-1 and
      connexin(Cx)43 in lipid rafts and its regulation of gap junctions. METHODS:
      N/N1003A lens epithelial cells, bovine primary lens epithelial cells, and stably
      transfected N/N1003A lens epithelial cells were used. Coimmunoprecipitation and
      Western blot analysis were used to detect protein expression and their
      interactions. Cav-1-containing lipid rafts and redistribution of Cav-1, PKCgamma,
      and Cx43 were analyzed by sucrose gradients and by consequent Western blot
      analysis. Cell surface gap junction Cx43 plaques were detected by confocal
      microscopy. PKCgamma activity was measured with a PKC assay kit. RESULTS: Cav-1
      and -2 were found in N/N1003A and bovine primary lens epithelial cells. Cx43 was
      associated with Cav-1 in lipid rafts. Phorbol ester (TPA) and insulin-like growth
      factor (IGF)-1 recruited PKCgamma into Cav-1-containing lipid rafts and
      stimulated the interactions of PKCgamma with Cav-1 and Cx43. TPA and IGF-1
      induced redistribution of Cav-1 and Cx43 from light-density fractions to higher
      density fractions on sucrose gradients. PKCgamma redistributed with Cav-1- and
      Cx43-containing fractions on stimulation with TPA or IGF-1. Overexpression of
      PKCgamma-enhanced green fluorescent protein (EGFP) increased the interaction of
      PKCgamma-EGFP with Cav-1 and Cx43 and decreased gap junction Cx43 plaques without
      exogenous growth factors. Overexpression of a loss-of-function PKCgamma mutant
      did not decrease gap junction Cx43 plaques or cause redistribution in lipid
      rafts, even though the PKCgamma mutant still interacted with Cav-1 and Cx43.
      CONCLUSIONS: Activation of PKCgamma by TPA or IGF-1 stimulated the interaction of
      PKCgamma with Cav-1 and Cx43 in lipid rafts, causing Cx43, Cav-1, and PKCgamma to
      redistribute within the lipid rafts, and this resulted in a decrease in gap
      junction plaques.

PMID- 14638726
TI  - Presence of a transcriptionally active glucocorticoid receptor alpha in lens
      epithelial cells.
AB  - PURPOSE: The purpose of this study was to determine whether lens epithelial cells
      (LECs) contain a glucocorticoid receptor (GR) that is transcriptionally active
      and that is able to induce production of known glucocorticoid-inducible proteins.
      METHODS: Protein and mRNA were obtained from human, rabbit, and bovine lens
      epithelia and from cultured human lens epithelial cells (B3, hLECs) and rabbit
      lens epithelial cells (N/N1003A, rLECs). Paraffin-embedded sections were prepared
      from human lenses for immunohistochemical localization of GR. RT-PCR was
      performed to amplify portions of GR, and the products were sequenced. Protein
      samples were analyzed by Western blot. hLECs and rLECs were transfected with
      pTAT3-luc and assayed for luciferase activity after treatment with dexamethasone
      (Dex) and/or RU486. Dex-treated LECs were also analyzed by quantitative real-time
      PCR and by Western blot for expression of specific mRNA and proteins. RESULTS: By
      PCR and sequencing, products consistent with GR sequences were obtained from
      human, rabbit, and bovine lenses and from hLECs and rLECs. The complete GRalpha
      sequence was obtained from rLECs and was found to be 89% identical with human GR.
      A 1757-bp 3' fragment of bovine GRalpha cDNA was also amplified from bovine lens.
      By Western blot, bands of approximately 94 kDa, the expected size of GR, were
      identified from human, rabbit, and bovine lens samples and from hLECs and rLECs,
      using anti-GR antibodies. Anti-GR antisera localized GR to both the cytosol of
      anterior and bow region LECs and to the nuclei of epithelial and early
      differentiating lens fiber cells. Luciferase expression was induced in pTAT3-luc
      transfected rLECs and hLECs by Dex treatment and this expression was partially
      (rLECs) or completely (hLECs) blocked by pretreatment with RU486. mRNA levels for
      type-1 glucocorticoid-induced target genes and also mRNA and protein levels for
      type-2 genes were upregulated after Dex exposure. CONCLUSIONS: The data confirm
      the existence of GR in hLECs, indicate that GR is present in rLECs, and resolve
      the controversy over the presence of GR in bovine lens. The GRalpha in hLECs and
      rLECs was shown to be transcriptionally active and the expression levels in hLECs
      of mRNAs and proteins known to be regulated by glucocorticoids were modified in
      these cells by glucocorticoid treatment.

PMID- 14638728
TI  - Methylglyoxal-derived hydroimidazolone advanced glycation end-products of human
      lens proteins.
AB  - PURPOSE: To determine the concentrations of methylglyoxal-derived advanced
      glycation end-products (AGEs), the hydroimidazolones MG-H1 and -H2, in soluble
      human lens proteins and compare them with the concentrations of other
      methylglyoxal-derived AGEs and pentosidine. METHODS: Lens protein samples were
      hydrolyzed enzymatically. AGEs were assayed without derivatization by HPLC with
      tandem mass spectrometry; the fluorescent AGEs argpyrimidine and pentosidine were
      assayed by fluorometric detection. MG-H1 and -H2 were resolved and assayed by
      fluorometric detection after derivatization with 6-aminoquinolyl-N
      hydroxysuccimidylcarbamate (AQC). RESULTS: The methylglyoxal-derived
      hydroimidazolones MG-H1 and -H2 were detected and quantified in human lens
      proteins. AGE concentrations (mean +/- SEM) were: MG-H1 4609 +/- 411 pmol/mg
      protein, MG-H2 3085 +/- 328 pmol/mg protein, argpyrimidine 205 +/- 19 pmol/mg
      protein, and pentosidine 0.693 +/- 0.104 pmol/mg protein. The concentration of MG
      H1 in human lens protein correlated positively with donor age (correlation
      coefficient = 0.28, P < 0.05), the concentration of MG-H2 (correlation
      coefficient = 0.78, P < 0.001) and argpyrimidine (correlation coefficient = 0.42,
      P < 0.01). The concentrations of AGEs were increased in cataractous lenses in
      comparison with noncataractous lenses: the increases were MG-H1 85%, MG-H2 122%,
      argpyrimidine 255%, and pentosidine 183% (P < 0.001). Multiple logistic
      regression analysis showed a significant link of cataract to donor age
      (regression coefficient beta = 0.094, P = 0.026) and argpyrimidine (beta = 0.022,
      P = 0.002). CONCLUSIONS: Methylglyoxal hydroimidazolones are quantitatively major
      AGEs of human lens proteins. These substantial modifications of lens proteins may
      stimulate further glycation, oxidation, and protein aggregation leading to the
      formation of cataract.

PMID- 14638727
TI  - Expression and activity of the signaling molecules for mitogen-activated protein
      kinase pathways in human, bovine, and rat lenses.
AB  - PURPOSE: The mitogen-activated protein kinase (MAPK) pathways play distinct roles
      in the lens. However, the expression patterns and activity levels of various
      components for these pathways have not been well-documented in vertebrate lenses,
      especially human lens. In the present study, the expressions and activities of
      extracellular signal-regulated kinase (ERK)-1/2/3, c-Jun NH2-terminal kinase
      (JNK)-1/2, p38 kinase, mitogen-activated protein kinase kinase (MEK)-1/2, and
      RAF1 were recorded in human, bovine, and rat lenses. METHODS: Human, bovine, and
      rat lenses were isolated from intact eyes. The epithelia and different layers of
      fiber cells were isolated from these lenses. Total proteins extracted from these
      samples were subject to analysis of the expression patterns and activity levels
      of the MAPKs and the activating kinases of ERK1/2. RESULTS: ERK1 and ERK2 were
      the most abundant MAPKs in terms of both protein and activity levels in all
      lenses. JNK1 and JNK2 were highly expressed in bovine lens, which differed from
      the pattern shared by human and rat lenses. p38 kinase was similarly expressed in
      bovine and rat lenses, but different from that in human lens. However, p38 kinase
      activity was exclusively detected in the epithelia. All lenses had MEK1/2
      activity in their epithelia but the expression patterns of MEK1 and MEK2 differed
      in these lenses. RAF1 was expressed in the epithelia of all lenses, but its
      activity was detected only in rat lens. CONCLUSIONS: ERK1 and ERK2 are the most
      abundant MAPKs in the ocular lens, providing the basis for their multiple
      functions in lens development and pathogenesis. The dominant epithelial
      distribution of JNK1/2 and p38 kinase suggests that the lens epithelium is a
      major site for stress response. ERK1, p38 kinase, and PKCalpha can be used as
      molecular markers for aging.

PMID- 14638729
TI  - The toxic and stress responses of cultured human retinal pigment epithelium
      (ARPE19) and human glial cells (SVG) in the presence of triamcinolone.
AB  - PURPOSE: To compare the cytotoxic effect of TA on human retinal pigment
      epithelium (ARPE19) and human glial (SVG) cells over a range of concentrations
      and durations of exposure. METHODS: TA (0.01-1 mg/mL) or vehicle (benzyl alcohol,
      0.025%) was added to the ARPE19 and SVG cultures on day 0 and then subsequently
      for 1, 3, or 5 days. The amount of cell proliferations with or without TA
      treatment was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. All samples were read in triplicate (n =
      4 in all cases). c-Fos, c-jun, caspase-3, c-myc, and p53 expression was
      determined after TA treatments after 0, 10, 20, 30, 40, 50, 60, and 90 minutes.
      All results were analyzed with ANOVA. RESULTS: TA (0.01-1 mg/mL) caused a
      significant reduction in ARPE19 cells that had been exposed to it for more than 1
      day. Significant reductions in the number of SVG cells were observed as early as
      day 1 at 0.1 and 1 mg/mL TA. In general, the level of remaining SVG cells was
      less than that of the APRE19 cells over the 5 days. SVG cells appeared more
      susceptible to TA. Caspase-3 was elevated in both ARPE19 and SVG cells after TA
      treatment. c-Fos and c-jun expression was also increased in ARPE19 cells but not
      in SVG. The vehicle of TA had no effect, and there was no change in p53 or c-myc
      expression. CONCLUSIONS: TA was cytotoxic to both SVG and ARPE19 cells, with
      higher efficacy on SVG. TA caused the activation of the caspase-3 pathway more
      readily than the cell-protective c-fos and c-jun pathways in SVG cells, making
      those cells more vulnerable than the ARPE19 cells. The results suggest that TA
      toxicity in one cell type may not reliably indicate its toxicity in other cells.
      Different cells within the retina may react to TA differently, or TA may cause
      changes in the gene expressions differentially with different concentrations of
      the same stimulus.

PMID- 14638730
TI  - Interactions of endothelin-1 with dexamethasone in primary cultured human
      trabecular meshwork cells.
AB  - PURPOSE: Concentrations of aqueous humor endothelin (ET)-1 are increased in
      patients with primary open-angle glaucoma (POAG) as well as in animal models of
      glaucoma. Glucocorticoids have also been associated with glaucoma, in that
      topical administration of glucocorticoids can increase intraocular pressure by
      increasing outflow resistance in the trabecular meshwork (TM) in some
      individuals. Recent research has shown that dexamethasone (Dex), a synthetic
      glucocorticoid, can increase the release of ET-1 from human nonpigmented ciliary
      epithelial (HNPE) cells, a source of aqueous ET-1. In the present study, the
      downstream interaction of ET-1 with Dex in target TM cells, an action that may
      alter outflow resistance, was investigated. METHODS: A normal primary human TM
      (NTM) cell line and a TM cell line derived from a glaucomatous eye (GTM) were
      used. The cells were treated with vehicle or Dex. The mRNA levels of prepro-ET-1,
      endothelin receptor A (ET(A)), and endothelin receptor B (ET(B)) were measured by
      quantitative RT-PCR (QPCR). The protein expression of ET(A) and ET(B) receptors
      were investigated by Western blot analysis using polyclonal anti-ET(A) and anti
      ET(B) antibodies, respectively, on plasma membrane fractions. Intracellular
      Ca(2+) ([Ca(2+)](i)) mobilization mediated by ET-1 was measured using the Fura-2
      AM fluorescent probe technique as an index of ET receptor function. ET-1
      stimulated nitric oxide (NO) release was measured using a Griess colorimetric NO
      synthase assay kit. RESULTS: Both NTM and GTM cultured cells expressed prepro-ET
      1 mRNA less abundantly than did HNPE cells, and Dex treatment had no effect on
      the mRNA expression of the ET-1 gene. TM cells expressed mRNA of ET(A) receptors
      as detected by QPCR, whereas the ET(B) message was not clearly delineated.
      Western blot analysis showed that both ET(A) and ET(B) receptor proteins were
      present. The ET(A) receptor was linked to calcium mobilization as ET-1 produced
      an increase in intracellular calcium release, and this increase was blocked with
      a selective ET(A) receptor antagonist. Dex failed to induce any change in the
      expression of the ET(A) receptor in both NTM and GTM cells, and this was
      supported by the absence of a Dex effect on the ET-1-induced calcium response.
      However, Dex treatment diminished ET(B) receptor protein expression and produced
      a decrease in ET-1-stimulated release of NO, a response mediated by ET(B)
      receptors in TM cells. CONCLUSIONS: The Dex-induced increase in ET-1 released by
      HNPE cells coupled to the downstream Dex-induced specific suppression of ET(B)
      receptor protein expression and declines in ET-1-mediated increase in NO released
      by TM cells could increase contraction and decrease relaxation of the TM and
      contribute to the declines in conventional aqueous humor outflow and increases in
      intraocular pressure that occur with glucocorticoids.

PMID- 14638731
TI  - Flicker light-induced vasodilatation in the human retina: effect of lactate and
      changes in mean arterial pressure.
AB  - PURPOSE: Diffuse luminance flicker light increases retinal and optic nerve head
      blood flow in animals and humans, but the exact mechanisms that mediate increased
      flow have yet to be identified. In the current study, the effect of increased
      plasma lactate levels on flicker-induced vasodilatation in the retina was
      investigated in three independent studies in healthy humans. METHODS: In the
      first study, plasma lactate concentrations were increased by bicycle exercise in
      12 volunteers, and the change in retinal vessel diameter to 8-Hz square-wave
      flicker stimulation was measured with the Zeiss Retinal Vessel Analyzer (Carl
      Zeiss Meditec, Oberkochen, Germany). In a different study, sodium lactate was
      administered intravenously, and flicker responses were measured in 12 subjects.
      As a control experiment accounting for pressure increases induced by exercise,
      the effect of elevated ocular perfusion pressure on the flicker response was
      investigated during tyramine infusion (n = 12). RESULTS: The increase in plasma
      lactate concentration during intravenous infusion from 1.3 +/- 0.4 to 6.3 mmol/L
      and during dynamic exercise from 1.2 +/- 0.3 to 9.4 mmol/L decreased flicker
      responses in retinal arteries from 5.3% +/- 0.9% to 1.7% +/- 0.6% (P < 0.001) and
      from 3.6% +/- 0.6% to 2.0% +/- 0.8% (P = 0.03), respectively. In contrast, an
      increase of mean blood pressure from 81 +/- 3 to 92 +/- 3 mm Hg after tyramine
      infusion had no significant effect on flicker-induced vasodilatation in retinal
      arteries and veins. CONCLUSIONS: The signaling between neuronal activity and flow
      response in the human retina is sensitive to changes in blood lactate levels,
      whereas changes in systemic blood pressure have no major effect. Whether an
      increased cytosolic redox impairment contributes to flicker-induced
      vasodilatation has yet to be clarified.

PMID- 14638732
TI  - Spatial pattern and temporal evolution of retinal oxygenation response in oxygen
      induced retinopathy.
AB  - PURPOSE: To determine the spatial pattern and temporal evolution of the change in
      retinal partial oxygen pressure (DeltaPO(2)) associated with a murine oxygen
      induced retinopathy (OIR) model of retinal neovascularization (NV). METHODS: On
      P7, newborn C57BL/6 mice were exposed to 75% oxygen until postnatal day (P)12,
      followed by recovery in room air until P17 or P34. Control mice remained in room
      air until P17 or P34. At P17 and P34, functional magnetic resonance imaging (MRI)
      and a carbogen inhalation challenge was used to measure retinal DeltaPO(2).
      Retinal avascularity, distance from the optic nerve head to the vascular edge in
      the peripheral retina, and NV incidence and severity were measured in retinas
      stained with adenosine diphosphatase (ADPase). RESULTS: In P17 and P34 controls
      and in P34 OIR animals, retinas were fully vascularized without evidence of NV.
      In P17 OIR mice, there was a large central retinal capillary-free zone (22% +/-
      3% of the entire retinal area, mean +/- SD) and 4 clockhours (range 1-7) of
      retinal NV at the border of the peripheral vascular and central acapillary retina
      in 100% (36/36) of the mice. In P17 OIR mice, retinal DeltaPO(2) over the
      vascularized far peripheral retina was not significantly (P > 0.05) different
      from the P17 control but was supernormal (P < 0.05) over the central capillary
      free retina. However, no differences (P > 0.05) in retinal DeltaPO(2) were found
      between the P34 control and OIR groups. CONCLUSIONS: A reversible supernormal
      DeltaPO(2) was found only over the central acapillary retina during the
      appearance of retinal NV in a mouse OIR model. The present data show the
      applicability of carbogen-challenge functional MRI to the study of retinal
      DeltaPO(2) in vivo in eyes that are too small for the use of existing techniques.

PMID- 14638733
TI  - A naturally occurring rat model of X-linked cone dysfunction.
AB  - PURPOSE: To describe the electrophysiological, histologic, and hereditary
      features of a naturally occurring rat model of cone function loss. METHODS: Dark-
      and light-adapted electroretinograms (ERGs) were used to evaluate retinal
      function. The thickness and architecture of the retina were observed by light
      microscopy. The cone density was investigated by wholemount immunocytochemistry.
      The inheritance pattern was defined by mating with control female rats. RESULTS:
      In affected rats, light-adapted ERGs were nearly absent, whereas dark-adapted
      responses were of normal amplitude with delays in b-wave implicit time. Overall
      retinal structure was normal at the light microscopic level. There was no
      difference in cone density between control and affected rats. The cone function
      abnormality is inherited as an X-linked trait. CONCLUSIONS: A spontaneous rat
      mutant was identified that has markedly affected cone function, whereas rod
      mediated function is largely spared. The presence of the normal number of cone
      outer segments indicates that the defect does not involve cone photoreceptor
      degeneration. This rat model provides a model of X-linked cone dysfunction, and
      may also be used to examine aspects of rod-mediated visual function in the rat.
      Further studies are needed to identify the gene that is involved.

PMID- 14638734
TI  - Diabetes-induced mitochondrial dysfunction in the retina.
AB  - PURPOSE: Oxidative stress is increased in the retina in diabetes, and
      antioxidants inhibit activation of caspase-3 and the development of retinopathy.
      The purpose of this study was to investigate the effect of diabetes on the
      release of cytochrome c from mitochondria and translocation of Bax into
      mitochondria in the rat retina and in the isolated retinal capillary cells.
      METHODS: Mitochondria and cytosol fractions were prepared from retina of rats
      with streptozotocin-induced diabetes and from the isolated retinal endothelial
      cells and pericytes incubated in 5 or 20 mM glucose medium for up to 10 days in
      the presence of superoxide dismutase (SOD) or a synthetic mimetic of SOD
      (MnTBAP). The release of cytochrome c into the cytosol and translocation of the
      proapoptotic protein Bax into the mitochondria were determined by the Western
      blot technique and cell death by caspase-3 activity and ELISA assay. RESULTS:
      Diabetes of 8 months' duration in rats increased the release of cytochrome c into
      the cytosol and Bax into the mitochondria prepared from the retina, and this
      phenomenon was not observed at 2 months of diabetes. Incubation of isolated
      retinal capillary cells with 20 mM glucose increased cytochrome c content in the
      cytosol and Bax in the mitochondria, and these abnormalities were accompanied by
      increased cell apoptosis. Inclusion of SOD or its mimetic inhibited glucose
      induced release of cytochrome c, translocation of Bax, and apoptosis.
      CONCLUSIONS: Retinal mitochondria become leaky when the duration of diabetes is
      such that capillary cell apoptosis can be observed; cytochrome c starts to
      accumulate in the cytosol and Bax into the mitochondria. Inhibition of
      superoxides inhibits glucose-induced release of cytochrome c and Bax and inhibits
      apoptosis in both endothelial cells and pericytes. Identifying the mechanism by
      which retinal capillary cells undergo apoptosis may reveal novel therapies to
      inhibit the development of retinopathy in diabetes.

PMID- 14638735
TI  - Automated measurement of microaneurysm turnover.
AB  - PURPOSE: An automated system for the measurement of microaneurysm (MA) turnover
      was developed and compared with manual measurement. The system analyses serial
      fluorescein angiogram (FA) or red-free (RF) fundus images; fluorescein
      angiography was used in this study because it is the more sensitive test for MAs.
      Previous studies have shown that the absolute number of MAs observed does not
      reflect the dynamic temporal nature of the MA population. In this study, almost
      half of the MAs present at baseline had regressed after a year and been replaced
      by new lesions elsewhere. METHODS: Two clinical datasets were used to evaluate
      the performance of the automated turnover measurement system. The first consisted
      of 10 patients who had two fluorescein angiograms acquired a year apart. These
      data were analyzed, both manually and using the automated system, to investigate
      the inter- and intraobserver variations associated with manual measurement and to
      assess the performance of the automated system. The second dataset contained FAs
      from a further 25 patients. This dataset was analyzed only with the automated
      system to investigate some properties of microaneurysm turnover, in particular
      the differing detection sensitivities of new, static and regressed
      microaneurysms. RESULTS: Manual measurements exhibited large inter- and
      intraobserver variation. The sensitivity and specificity of the automated system
      were similar to those of the human observers. However, the automated measurements
      were more consistent-an important condition for accurate turnover quantification.
      Regressed MAs were more difficult to detect reliably than new MAs, which were
      themselves more difficult to detect reliably than static MAs. CONCLUSIONS: The
      automated system was shown to be fast, reliable, and repeatable, making it
      suitable for processing large numbers of images. Performance was similar to that
      of trained manual observers.

PMID- 14638736
TI  - c-Jun expression in surviving and regenerating retinal ganglion cells: effects of
      intravitreal neurotrophic supply.
AB  - PURPOSE: To investigate c-jun expression in surviving and axon-regenerating
      retinal ganglion cells (RGCs) and the effect of intravitreal neurotrophic supply
      on c-jun expression. METHODS: All animals underwent optic nerve transection (ONT)
      0.5 mm behind the eyeball. Some animals underwent a replacement of the optic
      nerve with an autologous sciatic nerve graft (SNG) to allow axonal regrowth. To
      provide a neurotrophic supply, a peripheral nerve (PN) segment or brain-derived
      neurotrophic factor (BDNF)/ciliary neurotrophic factor (CNTF) was applied
      intravitreally. The time course of c-jun expression was first examined in both
      surviving and regenerating RGCs. Then, c-jun expression was examined in surviving
      and regenerating RGCs 3 weeks after intravitreal BDNF/CNTF treatment. Animals
      with vehicle eye injection were used as the control. Fluorescent dye was used for
      retrograde labeling of surviving (applied behind the eyeball) and regenerating
      (applied at the distal end of the SNG) RGCs. All retinas were
      immunohistochemically stained for c-jun. RESULTS: c-Jun was not detected in
      normal RGCs, but weak expression was seen in surviving RGCs after ON injury. The
      proportion of c-jun-positive (+) RGCs among surviving cell population was 52.6%
      to 86.5% 2 to 6 weeks after ONT. Among regenerating RGCs, more than 80% expressed
      c-jun in all treatment groups, a proportion that was significantly higher after
      CNTF treatment (90.7%). In addition, c-jun expression was much stronger in
      intensity and the c-jun(+) nuclei were much larger in regenerating than in
      surviving RGCs. CONCLUSIONS: c-Jun expression in RGCs was upregulated after
      injury. Most regenerating RGCs were c-jun(+), and the intensity of c-jun
      expression was higher in regenerating than in surviving RGCs. CNTF also
      upregulated c-jun expression in RGCs.

PMID- 14638737
TI  - Investigation of laser-induced choroidal neovascularization in the rat.
AB  - PURPOSE: Choroidal neovascularization plays an important role in pathogenesis of
      age-related macular degeneration. Induction of neovascularization by laser
      photocoagulation in the rat fundus is an established animal model in which the
      effects of new therapeutic approaches are assessed. The purpose of this study was
      to compare different detection methods of laser-induced neovascularization in the
      rat. METHODS: Laser spots were applied to the fundus of Long-Evans rats. Ten days
      after, four different methods were used to detect laser-induced
      neovascularization: (1) high-resolution angiography with fluorescein
      isothiocyanate-dextran, (2) immunohistochemical visualization of platelet
      endothelial cell adhesion molecule (PECAM)-1, (3) visualization of intravascular
      lumens by peroxidase perfusion in the living rat with subsequent histologic
      analysis, and (4) histochemical representation of alkaline phosphatase in
      endothelial cells. RESULTS: At the rim of the laser scars vessel-forming
      endothelial cells with intravasal dextran and peroxidase were present. Cross
      sections demonstrated that these vessels originated from the retina. The center
      of the scars contained homogenous endothelial cells of choroidal origin, which
      was confirmed by immunohistochemistry and electron microscopy. In laser-treated
      eyes without FITC-dextran perfusion, scars showed unspecific fluorescence, making
      differentiation from specific FITC-dextran-associated fluorescence difficult.
      CONCLUSIONS: In the rat model of laser-induced neovascularization, newly
      developed endothelial cells originate from the retina and the choroid. Whereas
      ring-like surrounding vessels come from the retina, flat endothelial cells in
      deeper layers are of choroidal origin or may originate from circulating
      endothelial precursor cells. Dextran angiography has to be regarded critically
      for visualizing the choriocapillaris and CNV in laser scars. PECAM-1
      immunohistochemistry is best for detection and quantification of
      neovascularization in laser scars.

PMID- 14638738
TI  - Methods and perceptual thresholds for short-term electrical stimulation of human
      retina with microelectrode arrays.
AB  - PURPOSE: To report methods for performing epiretinal electrical stimulation with
      microfabricated electrode arrays and determining perceptual thresholds on awake
      human volunteers during acute surgical trials. METHODS: Four hypotheses were
      tested: (1) epiretinal stimulation can be performed during acute experiments
      without obviously damaging the retina or degrading vision or the health of the
      eye; (2) perception can be obtained 50% of the time in blind patients with charge
      densities below published safety limits; (3) the minimal charge needed to induce
      perception would be higher in patients with more severe retinal degeneration; and
      (4) threshold charge would be lower at shorter stimulus durations. Five subjects
      with severe blindness from retinitis pigmentosa and one with normal vision (who
      underwent enucleation of the eye because of orbital cancer) were studied.
      Electrical stimulation of the retina was performed on awake volunteers by placing
      a single 250-microm diameter handheld needle electrode or a 10-microm thick
      microfabricated array of iridium oxide electrodes (400-, 100-, or 50-microm
      diameter) on the retina. Current sources outside the eye delivered charge to the
      electrodes. Assessment of damage was made by observing the clinical appearance of
      the eyes, comparing pre- and postoperative visual acuity, obtaining retinal
      histology in one case, and comparing perceptual thresholds with published safety
      limits. RESULTS: No clinically visible damage to the eye or loss of vision
      occurred. Even at sites removed from stimulation, histology revealed swollen
      photoreceptor inner and outer segments, which were believed to be nonspecific
      findings. Percepts could not be reliably elicited with 50-microm diameter
      electrodes using safe charges in one blind patient. With the two larger
      electrodes, only the normal-sighted patient had thresholds at charge densities
      below 0.25 and 1.0 millicoulombs (mC)/cm(2) for 400- and 100-microm diameter
      electrodes, respectively, which is one seemingly reasonable estimate of safety
      derived from the product of charge per phase and charge density per phase. In
      blind patients, thresholds always exceeded these levels, although most were close
      to these limits in patient 6. The range of charge density thresholds with the 400
      microm electrode in blind patients was 0.28 to 2.8 mC/cm(2). The normal-sighted
      patient had a threshold of 0.08 mC/cm(2) with a 400-microm electrode, roughly one
      quarter of the lowest threshold in the blind patients. Strength-duration curves
      obtained in two blind patients revealed the lowest threshold charge at the 0.25-
      or 1.0-ms stimulus duration. CONCLUSIONS: Threshold charge densities in severely
      blind patients were substantially higher than that in a normal-sighted patient.
      Charge densities in blind patients always exceeded one seemingly reasonable
      estimate of safe stimulation. The potential adversity of long-term stimulation of
      the retina by a prosthesis has yet to be determined.

PMID- 14638739
TI  - Perceptual efficacy of electrical stimulation of human retina with a
      microelectrode array during short-term surgical trials.
AB  - PURPOSE: This work is part of a feasibility assessment of a retinal prosthesis as
      a means to restore vision to patients with blindness caused by retinitis
      pigmentosa. The primary goal was to assess the concordance of the form of induced
      perception and the pattern of electrical stimulation of the retina, and the
      reproducibility of the responses. METHODS: Five volunteers with severe retinitis
      pigmentosa and one with normal vision were studied. A companion paper in this
      issue provides details on demographics, visual function, surgical methods,
      general stimulation strategy, and data analysis. Volunteers were awake during
      surgery while a 10-microm-thick, microfabricated electrode array was placed on
      the retina. The array was connected to extraocular current sources that delivered
      charges to 50-, 100-, and 400-microm-diameter electrodes. Negative control trials
      were randomly included. Perceptual quality was judged by the similarity between
      the form of stimulation and perception (i.e., accuracy) and the reproducibility
      of responses. RESULTS: Only 1 of 40 control tests yielded a false-positive
      result. On average, volunteers 3, 5, and 6 reported percepts that matched the
      stimulation pattern 48% and 32% of the time for single- and multiple-electrode
      trials, respectively. Two-point discrimination in the best cases may have been
      achieved in two blind subjects using (center-to-center) electrode separation of
      600 and 1960 microm. Reproducibility was achieved 66% of the time in the blind
      subjects. By comparison, in the normal-sighted subject, perceptual form was
      reported accurately 57% of the time, with 82% reproducibility, and two-point
      discrimination may have been achieved in one trial with 620-microm electrode
      spacing and in two trials each with 1860- and 2480-microm electrode spacing. In
      subjects 5 and 6, perceptual size was inconsistently related to the charge,
      although relatively large differences in charge (median: 0.55 microcoulombs
      [microC]) between two trials produced differently sized percepts. Longer stimuli
      did not produce rounder percepts. CONCLUSIONS: Single percepts induced by single
      electrode stimulation were relatively small, but the form of percepts, especially
      after multielectrode stimulation, often did not match the stimulation pattern,
      even in a normal-sighted volunteer. Reproducible percepts were more easily
      generated than those that matched the stimulation pattern.

PMID- 14638740
TI  - Reduced retinal angiogenesis in MMP-2-deficient mice.
AB  - PURPOSE: To study the putative role of endogenous matrix metalloproteinases
      (MMPs) in retinal neovascularization, an established mouse model was used to
      compare the retinal neovascularization observed in wild-type mice with that in
      mice without the MMP-2 or -9 genes. METHODS: C57Bl/6 (MMP-2(+/+) and -9(+/+)),
      MMP-2-deficient (MMP-2(-/-)), and MMP-9-deficient (MMP-9(-/-)) mice were used.
      After oxygen-induced retinopathy was induced in the mice, their eyes were rapidly
      removed and frozen in optimal cutting temperature embedding compound. Sections
      were histochemically stained with specific markers for vascular cells and
      angiogenesis-related factors. The area of new retinal vessels was measured using
      image-analysis software and compared between groups. RESULTS: Retinal
      neovascularization was not significantly different between wild-type and MMP-9(-/
      ) mice. The MMP-2(-/-) mice had significantly less extraretinal
      neovascularization than did wild-type mice. The mean number of extraretinal
      neovascular buds per cross section was significantly lower in MMP-2(-/-) mice
      than in wild-type mice (P < 0.05). The expression of other angiogenesis-related
      factors, vascular endothelial growth factor and pigment epithelium-derived
      factor, was not different between wild-type and MMP-2(-/-) mice. CONCLUSIONS: MMP
      2 may be essential in the regulation of retinal neovascularization. Pharmacologic
      intervention using MMP inhibitors may be a future therapeutic approach for
      angiogenic retinal diseases.

PMID- 14638741
TI  - High glucose alters connexin 43 expression and gap junction intercellular
      communication activity in retinal pericytes.
AB  - PURPOSE: To investigate the role of the gap junction protein, connexin-43 (Cx43)
      in the maintenance of retinal vascular homeostasis in diabetic retinopathy.
      METHODS: In human retinal pericytes (HRPs) and bovine retinal pericytes (BRPs)
      grown for 7 days in normal (5 mM) or high (30 mM)-glucose medium, the Cx43
      protein level was determined by Western blot analysis. Parallel experiments were
      performed in HRPs to determine the Cx43 mRNA level by RT-PCR, the distribution
      and localization of Cx43 protein by immunostaining, and gap junction
      intercellular communication (GJIC) activity by a scrape-loading dye transfer
      technique. Distribution and localization of Cx43 protein was also determined in
      pericyte-endothelial cell cocultures. RESULTS: Western blot analysis of the Cx43
      protein level in HRPs and BRPs indicated reduced Cx43 expression in the high
      glucose condition (69.1% +/- 17% of control, P = 0.004; 62.3% +/- 19% of control,
      P = 0.001, respectively). The Cx43 mRNA level in HRPs grown in high-glucose
      medium also showed significant reduction (71.4% +/- 16.8% of control, P = 0.02).
      The relative number of Cx43 plaques indicative of Cx43 localization at specific
      sites of contact between adjacent cells showed significant reduction in the high
      glucose condition (61% +/- 10% of control, P = 0.002); similarly, a significant
      reduction in the number of plaques was observed in cocultures grown in high
      glucose medium compared with those in normal medium (59.4% +/- 29% of control, P
      = 0.001). Cells with reduced Cx43 expression showed significantly reduced
      transfer of lucifer yellow (61% +/- 13% of control, P = 0.001; r = 0.9).
      CONCLUSIONS: High-glucose-induced downregulation of Cx43 expression and
      inhibition of GJIC in retinal pericytes may play a role in the disruption of
      vascular homeostasis in diabetic retinopathy.

PMID- 14638742
TI  - Mitogen-activated protein kinases and retinal ischemia.
AB  - PURPOSE: Mitogen-activated protein kinases (MAPKs), consisting of three major
      enzymes-extracellular signal-regulated kinase (ERK), p38, and c-jun N-terminal
      kinase (JNK)-couple cell-surface receptors to critical regulatory targets and
      gene transcription. We hypothesized that MAPKs are differentially expressed and
      have distinct functions after retinal ischemia. METHODS: Rats were subjected to
      retinal ischemia by elevation of intraocular pressure. Changes in MAPK expression
      were examined by Western blot of whole retinal homogenates and by
      immunohistochemistry of retinal cryosections. Phosphorylated (activated) ERK,
      p38, and JNK proteins were localized by fluorescent double labeling. The
      functional significance of activated MAPKs was assessed using pharmacological
      antagonists. Specific MAPK blockade was documented by kinase assay and
      immunohistochemistry for phosphorylated target proteins. The outcome after
      ischemia was examined with electroretinography (ERG), by measuring retinal cell
      layer thickness in paraffin-embedded sections, and by TUNEL staining on retinal
      cryosections. Data were analyzed using ANOVA and post hoc t-test, with P < 0.05
      considered significant. RESULTS: Expression of phosphorylated JNK and p38
      increased significantly after ischemia and followed a specific time course,
      beginning at 1 hour, and persisting up to 1 week later. JNK and p38 were
      expressed in the nuclei of ganglion and amacrine cells, the outer plexiform
      layer, the nerve fiber layer, and the axonal terminals of bipolar cells.
      Phosphorylated ERK was expressed in Muller cells, peaking at 1 to 6 hours after
      ischemia. Blocking activation of p38 or ERK significantly improved recovery of
      the ERG b-wave after ischemia, dramatically decreased thinning of the inner
      nuclear layers, and decreased the percentage of TUNEL-positive cells.
      CONCLUSIONS: The MAPKs each demonstrate a specific cellular distribution after
      ischemia, and ERK and p38 are linked to apoptosis. Blockade of p38 or ERK
      provides significant protection from ischemic damage, suggesting a novel
      therapeutic role for MAPK inhibition in neuroprotection.

PMID- 14638743
TI  - The expression of the Leber congenital amaurosis protein AIPL1 coincides with rod
      and cone photoreceptor development.
AB  - PURPOSE: The Leber congenital amaurosis (LCA) protein AIPL1 is present only in
      the rod photoreceptors of the adult human retina and is excluded from the cone
      photoreceptors. LCA, however, is characterized by an absence of both rod and cone
      function at birth or shortly thereafter. Therefore, this study was conducted to
      determine whether AIPL1 is present in the rod and cone photoreceptors of the
      developing human retina. In addition, the expression of NUB1, a putative AIPL1
      interacting partner, was examined. METHODS: A comprehensive spatiotemporal
      examination of AIPL1 distribution during development was performed by
      immunohistochemistry, using a previously characterized AIPL1 anti-serum.
      Immunofluorescence confocal microscopy was used to examine the coexpression of
      AIPL1 with the long/medium (L/M) and short (S) wavelength-sensitive cone
      photoreceptors in the developing human retina. The spatiotemporal distribution of
      NUB1 was also examined by immunohistochemistry, using a newly developed anti
      serum to the C terminus of NUB1. RESULTS: AIPL1 protein was detected by 11.8
      fetal weeks in the central fetal human retina. With continued development, AIPL1
      expression spread gradually toward peripheral retina. AIPL1 was expressed in the
      L/M and S cone photoreceptors in addition to the rods of the developing human
      retina. NUB1 was localized in cell nuclei throughout the human fetal and adult
      eye at all time points. CONCLUSIONS: The pattern of AIPL1 expression closely
      follows the centroperipheral gradient in photoreceptor development. The data
      suggest that AIPL1 is essential for the normal development of both rod and cone
      photoreceptor cells and that mutations in the AIPL1 gene cause the death or
      dysfunction of photoreceptors early in development resulting in blindness or
      severely impaired vision at birth.

PMID- 14638744
TI  - Opticin binds retinal growth hormone in the embryonic vitreous.
AB  - PURPOSE: Opticin is a small leucine-rich repeat proteoglycan that is abundant in
      several ocular tissues, including the vitreous. Like other proteoglycans, opticin
      may have the ability to bind and regulate the release of growth factors. Previous
      work has shown that isoforms of growth hormone (GH) are present in the embryonic
      retina, where they may act as a growth factor. The current study was conducted to
      investigate the possibility that opticin binds retinal GH in the vitreous of the
      chick embryo. METHODS: The vitreous and retina of embryonic day-8 chicks were
      examined for the presence of opticin and GH, by Western immunoblot analysis,
      coimmunoprecipitation, and immunocytochemistry. RESULTS: Opticin associated with
      GH in the embryonic vitreous to produce a 60- to 62-kDa complex. Opticin and GH
      were also colocalized in the retina in retinal ganglion cells. CONCLUSIONS: The
      binding of retinal GH by opticin in the vitreous suggests that GH, secreted by
      the retinal ganglion cells, may be sequestered and concentrated in the vitreous
      and could act there as a paracrine differentiation factor in ocular development.
      During development, opticin could therefore regulate growth factor-like actions
      of retinal GH, both in the vitreous and the retinal ganglion cells. The
      physiological roles of GH in this location remain to be determined, but may
      include the regulation of cell proliferation and cell death.

PMID- 14638745
TI  - Mapping the blood vessels with paracellular permeability in the retinas of
      diabetic rats.
AB  - PURPOSE: Diabetic retinopathy increases the permeability of the blood-retinal
      barrier, but the specific vessels that become permeable have not been identified.
      Both transcellular and paracellular pathways of vascular solute flux have been
      proposed. This study was conducted to test the hypothesis that paracellular flux
      contributes to increased retinal vascular permeability after VEGF treatment or
      diabetes, and to map the types of vessels that became permeable. METHODS: Regions
      of paracellular flux were identified by perfusion with fluorescent concanavalin A
      (ConA). Rats were injected intravitreally with VEGF or made diabetic with
      streptozotocin (STZ). After specified times, the rats were perfused with fixative
      followed by ConA, which binds to the basement membrane but not the luminal
      surface of endothelial cells. With this approach, ConA labels only blood vessels
      with paracellular permeability. Retinas were also labeled by immunofluorescence
      for the tight junction proteins occludin and claudin-5 and examined by confocal
      microscopy. RESULTS: ConA labeling increased in the superficial arterioles and
      postcapillary venules, 2 weeks after the onset of diabetes. After 1 month, ConA
      labeling dramatically increased and extended to the capillaries of the outer
      plexiform layer. There was an inverse relationship between occludin
      immunoreactivity and ConA binding, but no change in claudin-5 immunoreactivity
      was detected. Injection of VEGF gave similar results. CONCLUSIONS: Diabetes and
      VEGF increase paracellular vascular permeability in the retina, associated with
      redistribution of occludin. This permeability begins in the superficial
      arterioles and postcapillary venules and progresses to the capillary bed.

PMID- 14638746
TI  - Enhanced induction of RPE lineage markers in pluripotent neural stem cells
      engrafted into the adult rat subretinal space.
AB  - PURPOSE: To investigate the differentiation of rat neural stem cells (rNSCs) into
      cells of retinal pigment epithelial (RPE) lineage both in vitro and in vivo,
      after subretinal transplantation into normal rats and in a sodium iodate
      (NaIO(3)) model of RPE loss. METHODS: rNSCs prepared from the cortex of embryonic
      day (E)14 Fisher F344 rats were cocultured with different concentrations of
      vasoactive intestinal peptide (VIP), adult rat RPE cells, or neurosensory retina
      (NSR) for 5 days. Cell morphology and expression of RPE-specific markers
      (cytokeratin, CD68, microphthalmia-inducing transcription factor [MITF]) were
      studied. Additional antibodies used to characterize the rNSCs were markers for
      stem cells (nestin), immature neurons (betaIII-tubulin), astrocytes (glial
      fibrillary acidic protein [GFAP]), and oligodendrocytes (Rip). In in vivo
      studies, 10(6) green fluorescent protein [GFP]-labeled rNSCs were injected
      subretinally in either normal adult Lewis rats or NaIO(3)-treated rats (70 mg/mL
      NaIO(3) administered intravenously 7 days before transplantation). RESULTS: In
      vitro VIP-treated rNSCs changed from round cells to glia-like cells with
      processes that stained for both GFAP and nestin. In addition, small clusters of
      flattened, polygonal cells with an epithelial-cell-like shape that stained for
      cytokeratin and CD68 were observed. Coculture of rNSCs with RPE cells, but not
      with NSR, also led to cells of this phenotype. After transplantation, nestin(+)
      and GFP(+) rNSCs were visible subretinally as a transplant. In addition, more
      than 50% of transplanted rNSCs were cytokeratin(+) and CD68(+). CONCLUSIONS: Very
      few rNSCs differentiate in vitro into epithelial-like cells that express RPE
      specific markers. In vivo, this differentiation is remarkably enhanced after
      subretinal engraftment. Thus, transplantation of NSCs into the subretinal space
      may be a therapy for retinal diseases involving an RPE abnormality.

PMID- 14638747
TI  - Inhibition of retinal neovascularization by intravitreal injection of human rPAI
      1 in a rat model of retinopathy of prematurity.
AB  - PURPOSE: Restructuring of extracellular matrix at actively extending blood vessel
      tips involves secretion of plasminogen activator (PA). Findings in earlier
      studies conducted in the authors' laboratory have suggested that angiostatic
      steroids suppress the PA activity essential for the invasive aspect of
      angiogenesis by increasing synthesis of plasminogen activator inhibitor (PAI)-1.
      This experiment was designed to test the effect of administration of exogenous
      PAI-1 on retinal neovascularization (NV) in an animal model of retinopathy of
      prematurity (ROP). METHODS: At birth, Sprague-Dawley rats were placed into
      incubators and exposed to an atmosphere alternating between 50% and 10% O(2)
      every 24 hours. After 14 days, the animals were removed to room air, at which
      time each received a single intravitreal injection of 5 microL of buffer vehicle
      or one of five doses of PAI-1, ranging from 3.0 microg/mL to 2.0 mg/mL. Animals
      were killed 6 days later, and retinal NV was assessed using adenosine
      diphosphatase (ADPase) histochemical staining. RESULTS: Retinal
      neovascularization decreased with increasing PAI-1 dosage. The most effective
      dose tested (2.0 mg/mL) caused a 52% reduction in retinal NV relative to vehicle
      (P < 0.005). Normal vasculogenesis, as determined by measuring retinal vascular
      area, was unaffected. CONCLUSIONS: PAI-1 inhibits pathologic angiogenesis without
      adversely affecting normal vasculogenesis, an attractive feature for ROP
      therapies. Moreover, PAI's relationship to matrix metalloproteinases, which are
      also implicated in angiogenesis, suggests that the proteolytic aspect of the
      process may provide additional downstream therapeutic targets.

PMID- 14638748
TI  - RPE cells modulate subretinal neovascularization, but do not cause regression in
      mice with sustained expression of VEGF.
AB  - PURPOSE: Previous studies using models of choroidal neovascularization (CNV) in
      which the angiogenic stimulus is not sustained, have concluded that the retinal
      pigmented epithelium (RPE) causes regression of neovascularization (NV). However,
      the withdrawal of angiogenic stimuli may actually be the major modulator of NV,
      and RPE cells may simply be responding to withdrawal of the angiogenic stimuli or
      something released by NV because of the withdrawal. In this study, the long-term
      course of NV and the behavior of the RPE in rhodopsin/VEGF transgenic mice, in
      which there is a sustained angiogenic stimulus, was investigated. METHODS:
      Hemizygous mice from the V-6 line were killed at 0.75, 1, 3, 6, and 12 months
      after birth, and at each time point mRNA for VEGF, VEGF-R1, and VEGF-R2 was
      measured by RT-PCR. Some mice were perfused with fluorescein-labeled dextran and
      retinal flatmounts were examined by fluorescence microscopy. Light and electron
      microscopy was performed on Epon-embedded eyes. RESULTS: The mRNA levels for
      VEGF, VEGF-R1, and VEGF-R2 remained constant from the earliest to the latest time
      point. Retinal flatmounts showed numerous small areas of subretinal NV at 3 weeks
      and at 1 month, and there were a similar number of larger lesions. By 6 months,
      many of the individual NV lesions had grown together to form large networks of
      new vessels. At 12 months, NV networks were similar to those at 6 months, but
      some of the vessels were not perfused. Light microscopy showed serous retinal
      detachments overlying NV lesions in mice up to 3 months of age, but at 6 and 12
      months, the RPE completely surrounded new vessels and formed tight junctions to
      reestablish the outer blood-retinal barrier, and there were no serous
      detachments. Electron microscopy showed that compared with more acute NV lesions,
      chronic lesions contained thinner endothelial cells, similar to those of the
      choriocapillaris in that they had scant cytoplasm and numerous fenestrations, or
      pinocytotic vesicles with thick basement membrane surrounded by extracellular
      matrix (ECM). Bruch's membrane remained intact. CONCLUSIONS: Despite persistent
      high expression of VEGF and its receptors, NV stopped growing and reached a
      plateau in older V-6 mice. RPE cells modulated the NV by surrounding it and
      reestablishing the blood-retinal barrier, but did not cause regression, although
      some vessels in chronic lesions were not perfused. These data do not support the
      conclusion of several previously reported studies, that RPE cells cause
      regression of CNV.

PMID- 14638749
TI  - Monochromatic aberrations as a function of age, from childhood to advanced age.
AB  - PURPOSE: To describe monochromatic optical aberrations of the eye as a function
      of age. METHODS: One hundred fourteen subjects with a spherical equivalent within
      +/-3.50 D from emmetropia, corrected visual acuity of 20/40 or better, and normal
      findings in an ophthalmic examination were enrolled. The mean age was 43.2 +/-
      24.5 years (range, 5.7-82.3). Monochromatic optical aberrations were measured
      with a Hartmann-Shack wavefront sensor after pharmacological dilation and
      cycloplegia. RESULTS: For a 5-mm pupil and for third- to seventh-, third-, fourth
      , and fifth- to seventh-order aberrations, as well as for coma and spherical
      aberrations, the root mean square (RMS) error as a function of age was modeled by
      a second-order polynomial regression. It decreased progressively through
      childhood, adolescence, and early adulthood; reached a minimum level during the
      fourth decade of life, then increased progressively with age, to age 82. For a 5
      mm pupil, the mean modulation transfer function (MTF) was reduced in both the
      child-teenage (5-20 years; n = 29) and the elderly (61-82 years; n = 37) groups
      versus the middle-aged adult group (41-60 years; n = 24; P < 0.05). In young
      adults (21-40 years; n = 23) and elderly subjects, the MTF curves were very close
      and almost superimposed at spatial frequencies higher than 38 cyc/deg.
      CONCLUSIONS: Aberrations of the whole eye were objectively measured from early
      childhood to an advanced age, and the relationship between monochromatic
      aberrations and age has been shown to fit a quadratic model. The results suggest
      that the definition of emmetropization should be broadened to include the
      reduction of higher order aberrations.

PMID- 14638751
TI  - Review of the use of statistics in infection and immunity.

PMID- 14638752
TI  - Hepcidin: the missing link between hemochromatosis and infections.

PMID- 14638753
TI  - Genomic location and variation of the gene for CRS, a complement binding protein
      in the M57 strains of Streptococcus pyogenes.
AB  - All isolates of serotype M1 of group A streptococci possess a gene for
      streptococcal inhibitor of complement (SIC) in the mga regulon, which harbors
      genes for other virulence factors, such as M and M-like proteins, C5a peptidase,
      and a regulator. In serotype M57 the gene for a protein that is closely related
      to SIC (crs57) is located outside the mga regulon. We mapped the location of the
      crs57 gene in six strains of emm57 (gene encoding the M57 protein) sequence types
      to an intergenic region between the ABC transporter gene (SPy0778) and the gene
      for a small ribosomal protein (rpsU). The noncoding sequences on both sides of
      crs57 exhibited high degrees of identity to the corresponding regions of sic from
      M1 strains. This included one of the inverted repeat sequences of IS1562 but not
      the insertion element itself. These observations suggest that crs57 was recently
      acquired by serotype M57 or its progenitor via horizontal acquisition from
      serotype M1. The six emm57 sequence type isolates analyzed in this study belong
      to two distinct molecular types (vir types VT8 and VT101). Although the crs57
      sequences from VT8 strains had very few substitution mutations, the VT101 crs57
      sequence had a large number of such mutations. The CRS57 proteins from these
      strains are secretory products and have the ability to bind to complement
      proteins. All these proteins contain several tryptophan-rich repeats designated
      DWS motifs and internal repeat sequences. In all of these structural and
      biochemical characteristics CRS57 resembles SIC from M1 strains. Hence, CRS57 has
      a functional role similar to that of SIC in an M1 strain.

PMID- 14638754
TI  - Oxygen regulates invasiveness and virulence of group B streptococcus.
AB  - The facultative anaerobe group B Streptococcus (GBS) is an opportunistic pathogen
      of pregnant women, newborns, and the elderly. Although several virulence factors
      have been identified, environmental factors that regulate the pathogenicity of
      GBS have not been well characterized. Using the dynamic in vitro attachment and
      invasion system (DIVAS), we examined the effect of oxygen on the ability of GBS
      to invade immortalized human epithelial cells. GBS type III strain M781 invaded
      human epithelial cells of primitive neurons, the cervix, the vagina, and the
      endometrium in 5- to 400-fold higher numbers when cultured at a cell mass
      doubling time (t(d)) of 1.8 h than at a slower t(d) of 11 h. Invasion was optimal
      when GBS was cultured at a t(d) of 1.8 h in the presence of >or=5% oxygen and was
      significantly reduced without oxygen. Moreover, GBS grown in a chemostat under
      highly invasive conditions (t(d) of 1.8 h, with oxygen) was more virulent in
      neonatal mice than was GBS grown under suboptimal invasion conditions (t(d) of
      1.8 h, without oxygen), suggesting a positive association between in vitro
      invasiveness with DIVAS and virulence.

PMID- 14638755
TI  - Genetic basis for biosynthesis of the (alpha 1-->4)-linked N-acetyl-D-glucosamine
      1-phosphate capsule of Neisseria meningitidis serogroup X.
AB  - The genetic basis for biosynthesis of the (alpha1-->4)-linked N-acetyl-D
      glucosamine 1-phosphate capsule of Neisseria meningitidis serogroup X was
      defined. The biosynthesis gene cassette was a approximately 4.2-kb region located
      between ctrA of the capsule transport operon and galE, which encodes the UDP
      glucose-4-epimerase. This location was identical to the locations of the
      biosynthesis cassettes in other meningococcal serogroups. Three open reading
      frames unique to meningococcus serogroup X were identified. Deletion-insertion
      mutation and colony immunoblotting confirmed that these three genes were
      essential for serogroup X capsule expression, and the genes were designated xcbA,
      xcbB, and xcbC (serogroup X capsule biosynthesis). Reverse transcriptase PCR
      indicated that the xcbABC genes form an operon and are cotranscribed divergently
      from ctrA. XcbA exhibited 52% amino acid similarity to SacB, the putative capsule
      polymerase of meningococcus serogroup A, suggesting that it plays a role as the
      serogroup X capsule polymerase. An IS1016 element was found within the intergenic
      region separating ctrA and xcbA in multiple strains, and this element did not
      interfere with capsule expression.

PMID- 14638756
TI  - The Listeria monocytogenes lemA gene product is not required for intracellular
      infection or to activate fMIGWII-specific T cells.
AB  - Clearance of the intracellular bacterial pathogen Listeria monocytogenes requires
      antigen-specific CD8(+) T cells. Recently it was shown that activation of class
      Ib major histocompatibility complex (MHC)-restricted CD8(+) T cells alone is
      sufficient for immune protection against listeriae. A major component of the
      class Ib MHC-restricted T-cell response is T cells that recognize formylated
      peptide antigens presented by M3 molecules. Although three N-formylated peptides
      derived from L. monocytogenes are known to bind to M3 molecules, fMIGWII is the
      immunodominant epitope presented by M3 during infection of mice. The source of
      fMIGWII peptide is the L. monocytogenes lemA gene, which encodes a 30-kDa protein
      of unknown function. In this report, we describe the generation of two L.
      monocytogenes lemA deletion mutants. We show that lemA is not required for growth
      of listeriae in tissue culture cells or for virulence during infection of mice.
      Surprisingly, we found that fMIGWII-specific T cells were still primed following
      infection with lemA mutant listeriae, suggesting that L. monocytogenes contains
      at least one additional antigen that is cross-reactive with the fMIGWII epitope.
      This cross-reactive antigen appears to be a small protease-resistant molecule
      that is secreted by L. monocytogenes.

PMID- 14638757
TI  - Divergent interactions of Ehrlichia chaffeensis- and Anaplasma phagocytophilum
      infected leukocytes with endothelial cell barriers.
AB  - Human anaplasmosis (formerly human granulocytic ehrlichiosis) and human monocytic
      ehrlichiosis (HME) are emerging tick-borne infections caused by obligate
      intracellular bacteria in the family Anaplasmataceae. Clinical findings include
      fever, headache, myalgia, leukopenia, thrombocytopenia, and hepatic inflammatory
      injury. Whereas Ehrlichia chaffeensis (HME) often causes meningoencephalitis,
      this is rare with Anaplasma phagocytophilum infection. The abilities of infected
      primary host monocytes and neutrophils and of infected HL-60 cells to cross human
      umbilical vein endothelial cell-derived EA.hy926 cell barriers and human brain
      microvascular cells (BMEC), a human blood-brain barrier model, were studied.
      Uninfected monocyte/macrophages crossed endothelial cell barriers six times more
      efficiently than neutrophils. More E. chaffeensis-infected monocytes
      transmigrated than uninfected monocytes, whereas A. phagocytophilum suppressed
      neutrophil transmigration. Differences were not due to barrier dysfunction, as
      transendothelial cell resistivities were the same for uninfected cell controls.
      Similar results were obtained for HL-60 cells used as hosts for E. chaffeensis
      and A. phagocytophilum. Differential transmigration of E. chaffeensis- and A.
      phagocytophilum-infected leukocytes and HL-60 cells confirmed a role for the
      pathogen in modifying cell migratory capacity. These results support the
      hypothesis that Anaplasmataceae intracellular infections lead to unique pathogen
      specific host cell functional alterations that are likely important for pathogen
      survival, pathogenesis, and disease induction.

PMID- 14638758
TI  - Association of Salmonella enterica serovar enteritidis yafD with resistance to
      chicken egg albumen.
AB  - Salmonella enterica serovar Enteritidis is a major cause of food-borne diseases
      in industrialized countries. The incidence of S. enterica serovar Enteritidis
      infections has increased substantially in recent decades, and S. enterica serovar
      Enteritidis is now one of the leading serovars of Salmonella in the United
      States. A unique epidemiological characteristic of S. enterica serovar
      Enteritidis is its association with chicken shell eggs, since approximately 80%
      of all human gastrointestinal diseases can be traced to contaminated egg
      products. Eggs are contaminated when bacteria from reproductive tissues of
      infected hens are packaged into the eggs and persist inside the hostile egg
      albumen environment. Therefore, resistance to egg albumen is an important aspect
      in the transmission of S. enterica serovar Enteritidis. We identified a gene,
      yafD from S. enterica serovar Enteritidis, whose overexpression conferred upon S.
      enterica serovar Typhimurium enhanced resistance to egg albumen, while disruption
      of this gene in S. enterica serovar Enteritidis rendered the organism more
      susceptible to egg albumen. YafD is homologous to members of an exonuclease
      endonuclease-phosphatase family, including some enzymes involved in DNA repair.
      Furthermore, we discovered that egg albumen has nuclease activities and uses both
      circular and linear DNA as substrates. We propose that YafD provides a survival
      advantage to S. enterica serovar Enteritidis in eggs by repairing DNA damage
      caused by egg albumen and that it may be one of the biologic determinants that
      contribute to the epidemiological association of S. enterica serovar Enteritidis
      with egg products.

PMID- 14638759
TI  - Plasmodium falciparum is able to invade erythrocytes through a trypsin-resistant
      pathway independent of glycophorin B.
AB  - Plasmodium falciparum invades erythrocytes through multiple ligand-receptor
      interactions, with redundancies in each pathway. One such alternate pathway is
      the trypsin-resistant pathway that enables P. falciparum to invade trypsin
      treated erythrocytes. Previous studies have shown that this trypsin-resistant
      pathway is dependent on glycophorin B, as P. falciparum strains invade trypsin
      digested glycophorin B-deficient erythrocytes at a highly reduced efficiency.
      Furthermore, in a recent study, the P. falciparum 7G8 strain did not invade
      glycophorin B-deficient erythrocytes, a finding that was not confirmed in the
      present study. To analyze the degree of dependence on glycophorin B for invasion
      by P. falciparum through the trypsin-resistant pathway, we have studied the
      invasion phenotypes of five parasite strains, 3D7, HB3, Dd2, 7G8, and Indochina
      I, on trypsin-treated normal and glycophorin B-deficient erythrocytes. Invasion
      was variably reduced in glycophorin B-deficient erythrocytes. Four strains, 3D7,
      HB3, Dd2, and Indochina I, invaded trypsin-treated erythrocytes, while invasion
      by the 7G8 strain was reduced by 90%. Among the four strains, invasion by 3D7,
      HB3, and Dd2 of trypsin-digested glycophorin B-deficient erythrocytes was further
      reduced. However, Indochina I invaded trypsin-digested glycophorin B-deficient
      erythrocytes at the same efficiency as its invasion of trypsin-digested normal
      erythrocytes. This strongly suggests that the Indochina I strain of P. falciparum
      is not dependent on glycophorin B to invade through a trypsin-resistant pathway
      as are the strains 3D7, HB3, and Dd2. Thus, P. falciparum is able to invade
      erythrocytes through a glycophorin B-independent, trypsin-resistant pathway.

PMID- 14638760
TI  - Lipopolysaccharide binding protein is an essential component of the innate immune
      response to Escherichia coli peritonitis in mice.
AB  - Lipopolysaccharide (LPS) binding protein (LBP) is an acute-phase protein that
      enhances the responsiveness of immune cells to LPS by virtue of its capacity to
      transfer LPS to CD14. To determine the role of LBP in the innate immune response
      to peritonitis, LBP gene-deficient (LBP(-/-)) and normal wild-type mice were
      intraperitoneally infected with Escherichia coli, the most common causative
      pathogen of this disease. LBP was detected at low concentrations in peritoneal
      fluid of healthy wild-type mice, and the local LBP levels increased rapidly upon
      induction of peritonitis. LBP(-/-) mice were highly susceptible to E. coli
      peritonitis, as indicated by accelerated mortality, earlier bacterial
      dissemination to the blood, impaired bacterial clearance in the peritoneal
      cavity, and more severe remote organ damage. LBP(-/-) mice displayed diminished
      early tumor necrosis factor alpha, interleukin-6, cytokine-induced neutrophil
      chemoattractant, and macrophage inflammatory protein 2 production and attenuated
      recruitment of polymorphonuclear leukocytes to the site of infection, indicating
      that acute inflammation was promoted by LBP. Locally produced LBP is an essential
      component of an effective innate immune response to E. coli peritonitis.

PMID- 14638761
TI  - Listeria monocytogenes mutants that fail to compartmentalize listerolysin O
      activity are cytotoxic, avirulent, and unable to evade host extracellular
      defenses.
AB  - Listeria monocytogenes is a facultative intracellular bacterial pathogen that
      escapes from a phagosome and grows in the host cell cytosol. Escape of the
      bacterium from the phagosome to the cytosol is mediated by the bacterial pore
      forming protein listeriolysin O (LLO). LLO has multiple mechanisms that optimize
      activity in the phagosome and minimize activity in the host cytosol. Mutants that
      fail to compartmentalize LLO activity are cytotoxic and have reduced virulence.
      We sought to determine why cytotoxic bacteria have attenuated virulence in the
      mouse model of listeriosis. In this study, we constructed a series of strains
      with mutations in LLO and with various degrees of cytotoxicity. We found that the
      more cytotoxic the strain in cell culture, the less virulent it was in mice.
      Induction of neutropenia increased the relative virulence of the cytotoxic
      strains 100-fold in the spleen and 10-fold in the liver. The virulence defect was
      partially restored in neutropenic mice by adding gentamicin, an antibiotic that
      kills extracellular bacteria. Additionally, L. monocytogenes grew more slowly in
      extracellular fluid (mouse serum) than within tissue culture cells. We concluded
      that L. monocytogenes controls the cytolytic activity of LLO to maintain its
      nutritionally rich intracellular niche and avoid extracellular defenses of the
      host.

PMID- 14638762
TI  - Biochemical and immunological characterization of bacterially expressed and
      refolded Plasmodium falciparum 42-kilodalton C-terminal merozoite surface protein
      1.
AB  - Protection against Plasmodium falciparum can be induced by vaccination in animal
      models with merozoite surface protein 1 (MSP1), which makes this protein an
      attractive vaccine candidate for malaria. In an attempt to produce a product that
      is easily scaleable and inexpensive, we expressed the C-terminal 42 kDa of MSP1
      (MSP1(42)) in Escherichia coli, refolded the protein to its native form from
      insoluble inclusion bodies, and tested its ability to elicit antibodies with in
      vitro and in vivo activities. Biochemical, biophysical, and immunological
      characterization confirmed that refolded E. coli MSP1(42) was homogeneous and
      highly immunogenic. In a formulation suitable for human use, rabbit antibodies
      were raised against refolded E. coli MSP1(42) and tested in vitro in a P.
      falciparum growth invasion assay. The antibodies inhibited the growth of
      parasites expressing either homologous or heterologous forms of P. falciparum
      MSP1(42). However, the inhibitory activity was primarily a consequence of
      antibodies directed against the C- terminal 19 kDa of MSP1 (MSP1(19)).
      Vaccination of nonhuman primates with E. coli MSP1(42) in Freund's adjuvant
      protected six of seven Aotus monkeys from virulent infection with P. falciparum.
      The protection correlated with antibody-dependent mechanisms. Thus, this new
      construct, E. coli MSP1(42), is a viable candidate for human vaccine trials.

PMID- 14638763
TI  - Modulation of polymorphonuclear cell interleukin-8 secretion by human monoclonal
      antibodies to type 8 pneumococcal capsular polysaccharide.
AB  - Pneumococcal capsular polysaccharide (PS) vaccines induce type-specific
      immunoglobulin M (IgM), IgG, and IgA. Type-specific IgG to the PS is sufficient
      to confer protection against the homologous serotype of the pneumococcus, but the
      efficacies of type-specific IgM and IgA are less well understood. We examined the
      in vitro activities and efficacies in mice of two human monoclonal antibodies
      (MAbs) to type 8 PS, NAD (IgA) and D11 (IgM). MAb-mediated opsonophagocytic
      killing was evaluated after coculture of type 8 pneumococci with human
      polymorphonuclear cells (PMNs), type-specific or control MAbs, and human
      complement sources. The effects of the MAbs on PMN interleukin-8 (IL-8) and IL-6
      secretion were determined in supernatants from cocultures containing pneumococci
      and PMNs by enzyme-linked immunosorbent assay. MAb efficacy was determined in an
      intratracheal model of type 8 infection in mice with classical complement pathway
      deficiency. Both MAbs were protective in 100% of infected mice. Neither MAb
      promoted a significant amount of killing of type 8 pneumococci compared to its
      isotype control MAb. Both type-specific MAbs mediated complement-dependent
      modulation of PMN IL-8 secretion, with increased secretion at effector/target
      (E:T) ratios of 500:1 and 50:1 and reduced secretion at 1:5. Trypan blue staining
      revealed that PMNs cocultured with D11 were less viable at an E:T ratio of 1:5
      than PMNs cocultured with the control MAb. PMN IL-6 secretion was increased by
      both type-specific and control MAbs. These results suggest that certain type
      specific IgM and IgAs might contribute to host defense by modulation of the
      inflammatory response to pneumococci.

PMID- 14638764
TI  - Identification of dimethyl sulfoxide reductase in Actinobacillus pleuropneumoniae
      and its role in infection.
AB  - Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia,
      is capable of persisting in oxygen-deprived surroundings, namely, tonsils and
      sequestered necrotic lung tissue. Utilization of alternative terminal electron
      acceptors in the absence of oxygen is a common strategy in bacteria under
      anaerobic growth conditions. In an experiment aimed at identification of genes
      expressed in vivo, the putative catalytic subunit DmsA of anaerobic dimethyl
      sulfoxide reductase was identified in an A. pleuropneumoniae serotype 7 strain.
      The 90-kDa protein exhibits 85% identity to the putative DmsA protein of
      Haemophilus influenzae, and its expression was found to be upregulated under
      anaerobic conditions. Analysis of the unfinished A. pleuropneumoniae genome
      sequence revealed putative open reading frames (ORFs) encoding DmsB and DmsC
      proteins situated downstream of the dmsA ORF. In order to investigate the role of
      the A. pleuropneumoniae DmsA protein in virulence, an isogenic deletion mutant,
      A. pleuropneumoniae DeltadmsA, was constructed and examined in an aerosol
      infection model. A. pleuropneumoniae DeltadmsA was attenuated in acute disease,
      which suggests that genes involved in oxidative metabolism under anaerobic
      conditions might contribute significantly to A. pleuropneumoniae virulence.

PMID- 14638765
TI  - Salivary antibodies directed against outer membrane proteins of Moraxella
      catarrhalis in healthy adults.
AB  - Moraxella catarrhalis is a major mucosal pathogen of the human respiratory tract,
      but the mucosal immune response directed against surface components of this
      organism has not been characterized in detail. The aim of this study was to
      investigate the salivary immunoglobulin A (IgA) response toward outer membrane
      proteins (OMP) of M. catarrhalis in healthy adults, the group of individuals
      least likely to be colonized and thus most likely to display mucosal immunity.
      Unstimulated saliva samples collected from 14 healthy adult volunteers were
      subjected to IgA immunoblot analysis with OMP preparations of M. catarrhalis
      strain O35E. Immunoblot analysis revealed a consistent pattern of IgA reactivity,
      with the appearance of five major bands located at >250, 200, 120, 80, and 60
      kDa. Eleven (79%) of 14 saliva samples elicited reactivity to all five bands.
      Immunoblot analysis with a set of isogenic knockout mutants lacking the
      expression of individual OMP was used to determine the identities of OMP giving
      rise to IgA bands. Human saliva was shown consistently to exhibit IgA-binding
      activity for oligomeric UspA2 (>250 kDa), hemagglutinin (200 kDa), monomeric
      UspA1 (120 kDa), transferrin-binding protein B (TbpB), monomeric UspA2, CopB, and
      presumably OMP CD. TbpB, oligomeric UspA2, and CopB formed a cluster of bands at
      about 80 kDa. These data indicate that the human salivary IgA response is
      directed consistently against a small number of major OMP, some of which are
      presently considered vaccine candidates. The functional properties of these
      mucosal antibodies remain to be elucidated.

PMID- 14638766
TI  - Porphyromonas gingivalis lipopolysaccharide antagonizes Escherichia coli
      lipopolysaccharide at toll-like receptor 4 in human endothelial cells.
AB  - E. coli lipopolysaccharide (LPS) induces cytokine and adhesion molecule
      expression via the toll-like receptor 4 (TLR4) signaling complex in human
      endothelial cells. In the present study, we investigated the mechanism by which
      Porphyromonas gingivalis LPS antagonizes E. coli LPS-dependent activation of
      human endothelial cells. P. gingivalis LPS at 1 micro g/ml inhibited both E. coli
      LPS (10 ng/ml) and Mycobacterium tuberculosis heat shock protein (HSP) 60.1 (10
      micro g/ml) stimulation of E-selectin mRNA expression in human umbilical vein
      endothelial cells (HUVEC) without inhibiting interleukin-1 beta (IL-1beta)
      stimulation. P. gingivalis LPS (1 micro g/ml) also blocked both E. coli LPS
      dependent and M. tuberculosis HSP60.1-dependent but not IL-1beta-dependent
      activation of NF-kappaB in human microvascular endothelial (HMEC-1) cells,
      consistent with antagonism occurring upstream from the TLR/IL-1 receptor adaptor
      protein, MyD88. Surprisingly, P. gingivalis LPS weakly but significantly
      activated NF-kappaB in HMEC-1 cells in the absence of E. coli LPS, and the P.
      gingivalis LPS-dependent agonism was blocked by transient expression of a
      dominant negative murine TLR4. Pretreatment of HUVECs with P. gingivalis LPS did
      not influence the ability of E. coli LPS to stimulate E-selectin mRNA expression.
      Taken together, these data provide the first evidence that P. gingivalis LPS
      dependent antagonism of E. coli LPS in human endothelial cells likely involves
      the ability of P. gingivalis LPS to directly compete with E. coli LPS at the TLR4
      signaling complex.

PMID- 14638767
TI  - Characterization and development of T-Cell immune responses in B-cell-deficient
      (Igh-6(-/-)) mice with Salmonella enterica serovar Typhimurium infection.
AB  - Infection of mice with Salmonella enterica serovar Typhimurium induces strong Th1
      T-cell responses that are central to the control of the infection. In the present
      study, we examined the role of B cells in the development of Th1 T-cell responses
      to Salmonella by using gene-targeted B-cell-deficient mice (Igh-6(-/-) mice). The
      development of Th1 T-cell responses in Igh-6(-/-) mice was impaired in the early
      stage of a primary infection. This impairment persisted throughout the course of
      the disease. The ability of T cells to produce the Th1 cytokine gamma interferon
      and the frequency at which they did so were lower in Igh-6(-/-) mice than in
      control mice. We also observed a transient switch toward Th2 cytokine production
      in Igh-6(-/-) mice. Thus, B cells are important for the induction of protective
      Th1 T-cell responses in the early phase of a Salmonella infection. Activated B
      cells express high levels of major histocompatibility complex and costimulatory
      molecules and are nearly as effective as dendritic cells in their antigen
      presenting cell (APC) activity. However, their importance as APCs in infection
      and their role in initiating and/or maintaining T-cell responses are unknown.
      Here, we show that B cells upregulate costimulatory molecules upon in vitro
      stimulation with S. enterica serovar Typhimurium and that they can present
      Salmonella antigens to Salmonella-specific CD4(+) T cells. Our results show that
      B cells are important for the development of T-cell responses in the early stage
      of a Salmonella infection and that this property may be due to their ability to
      present antigens to T cells.

PMID- 14638768
TI  - Resistance and susceptibility to filarial infection with Litomosoides sigmodontis
      are associated with early differences in parasite development and in localized
      immune reactions.
AB  - In order to understand natural resistance to filariasis, we compared Litomosoides
      sigmodontis primary infection of C57BL/6 mice, which eliminate the worms before
      patency, and BALB/c mice, in which worms complete their development and produce
      microfilariae. Our analysis over the first month of infection monitoredmigration
      of the infective larvae from the lymph nodes to the pleural cavity, where the
      worms settle. Although immune responses from the mouse strains differed from the
      outset, the duration of lymphatic migration (4 days) and filarial recovery rates
      were similar, thus confirming that the proportion of larvae that develop in the
      host species upon infection is not influenced by host genetic variability. The
      majority of worms reached the adult stage in both mouse strains; however, worm
      growth and molting were retarded in resistant C57BL/6 mice. Surprisingly, the
      only immune responses detected at 60 h postinfection occurred in the susceptible
      mice and only upon stimulation of cells from lymph nodes draining the inoculation
      site with infective larva extract: massive production of interleukin-6 (IL-6) and
      IL-5 (the latter cytokine was previously suspected to have an effect on L.
      sigmodontis growth). However, between days 10 and 30 postinfection,
      extraordinarily high levels of type 1 and type 2 cytokines and expansion of
      pleural leukocyte infiltration were seen in the resistant C57BL/6 mice,
      explaining the destruction of worms later. Our results suggest that events early
      in the infection determine susceptibility or resistance to subsequent
      microfilarial production and a parasite strategy to use specific immune responses
      to its own benefit.

PMID- 14638769
TI  - The site of Leishmania major infection determines disease severity and immune
      responses.
AB  - Inbred strains of mice infected with Leishmania major have been classified as
      genetically resistant or susceptible on the basis of their ability to cure their
      lesions, the parasite burden in the draining lymph nodes, and their type of T
      helper cell immune responses to the parasite. Using the intradermal infection at
      the base of the tail and the ear pinna, we compared for the first time the above
      mentioned parameters in six strains of mice infected with metacyclic
      promastigotes, and we show that the severity of disease depends greatly on the
      site of infection. Although the well-documented pattern of disease susceptibility
      of BALB/c and C57BL/6 mice described for the footpad and base-of-the-tail models
      of leishmaniasis were confirmed, C3H/HeN and DBA/2 mice, which are intermediate
      and susceptible, respectively, in the tail and other models, were resistant to
      ear infection. Moreover, in the CBA/H, C3H/HeN, C57BL/6J, and DBA/2 mouse
      strains, there was little correlation between the pattern of cytokines produced
      and the disease phenotype observed at the ear and tail sites. We conclude that
      the definition of susceptibility and the immune mechanisms leading to
      susceptibility or resistance to infection may differ substantially depending on
      the route of infection.

PMID- 14638770
TI  - Specificity and mechanism of immunoglobulin M (IgM)- and IgG-dependent protective
      immunity to larval Strongyloides stercoralis in mice.
AB  - Protective immunity in mice to the infective third-stage larvae (L3) of
      Strongyloides stercoralis was shown to be dependent on immunoglobulin M (IgM),
      complement activation, and granulocytes. The objectives of the present study were
      to determine whether IgG was also a protective antibody isotype and to define the
      specificity and the mechanism by which IgG functions. Purified IgG recovered from
      mice 3 weeks after a booster immunization with live L3 was shown to transfer high
      levels of protective immunity to naive mice. IgG transferred into mice treated to
      block complement activation or to eliminate granulocytes failed to kill the
      challenge larvae. Transfer of immune IgG into IL-5 knockout (KO) mice, which are
      deficient in eosinophils, resulted in larval attrition, while transfer into
      FcRgamma KO mice did not result in larval killing. These findings suggest that
      IgG from mice immunized with live L3 requires complement activation and
      neutrophils for killing of L3 through an antibody-dependent cellular cytotoxicity
      (ADCC) mechanism. This is in contrast to the results of investigations using IgM
      from mice immunized with live L3 and IgG from mice immunized with larval antigens
      soluble in deoxycholate in which protective immunity was shown to be ADCC
      independent. Western blot analyses with immune IgM and IgG identified few
      antigens recognized by all protective antibody isotypes. Results from
      immunoelectron microscopy demonstrated that the protective antibodies bound to
      different regions in the L3. It was therefore concluded that while IgM and IgG
      antibodies are both protective against larval S. stercoralis, they recognize
      different antigens and utilize different killing mechanisms.

PMID- 14638771
TI  - Conformational epitopes recognized by protective anti-neisserial surface protein
      A antibodies.
AB  - NspA is a conserved membrane protein that elicits protective antibody responses
      in mice against Neisseria meningitidis. A recent crystallographic study showed
      that NspA adopts an eight-stranded beta-barrel structure when reconstituted in
      detergent. In order to define the segments of NspA-containing epitopes recognized
      by protective murine anti-NspA antibodies, we studied the binding of two
      bactericidal and protective anti-NspA monoclonal antibodies (MAbs), AL12 and
      14C7. Neither MAb binds to overlapping synthetic peptides (10-mers, 12-mers, and
      cyclic 12-mers) corresponding to the entire mature sequence of NspA, or to
      denatured recombinant NspA (rNspA), although binding to the protein can be
      restored by refolding in liposomes. Based on the ability of the two MAbs to bind
      to Escherichia coli microvesicles prepared from a set of rNspA variants created
      by site-specific mutagenesis, the most important contacts between the MAbs and
      NspA appear to be located within the LGG segment of loop 3. The conformation of
      loop 2 also appears to be an important determinant, as particular combinations of
      residues in this segment resulted in loss of antibody binding. Thus, the two anti
      NspA MAbs recognize discontinuous conformational epitopes that result from the
      close proximity of loops 2 and 3 in the three-dimensional structure of NspA. The
      data suggest that optimally immunogenic vaccines using rNspA will require
      formulations that permit proper folding of the protein.

PMID- 14638772
TI  - An enzymatically active a domain is required for cholera-like enterotoxins to
      induce a long-lived blockade on the induction of oral tolerance: new method for
      screening mucosal adjuvants.
AB  - The cholera-like enterotoxins (CLETS), cholera toxin (CT) and Escherichia coli
      heat-labile toxin (LT), are powerful mucosal adjuvants. Here we show that these
      toxins also induce a long-lived blockade (of at least 6 months) on the induction
      of oral tolerance when they are coadministered with the antigen ovalbumin.
      Strikingly, only enzymatically active CLETS induced this blockade on the
      induction of oral tolerance. In this regard, the enzymatically inactive mutants
      of CT and LT, CTK63 and LTK63, and their recombinant B pentamers, rCTB and rLTB,
      failed to block the induction of oral tolerance, demonstrating a stringent
      requirement for an enzymatically active A domain in this phenomenon. Together
      with the results of other recent studies, these results indicate that the
      enzymatic activity of CLETS, most likely cyclic AMP elevation, is responsible for
      their adjuvant effects. The results of this study also indicate that measuring
      the ability of putative mucosal adjuvants to block the induction of oral
      tolerance may be a superior method for measuring mucosal adjuvanticity.

PMID- 14638773
TI  - Subtractive hybridization identifies a novel predicted protein mediating
      epithelial cell invasion by virulent serotype III group B Streptococcus
      agalactiae.
AB  - Group B Streptococcus agalactiae bacteria (group B streptococci [GBS]) are the
      most common cause of serious bacterial infection in newborn infants. The majority
      of serotype III-related cases of neonatal disease are caused by a genetically
      related subgroup of bacteria, restriction fragment digest pattern (RDP) type III
      3, suggesting that these strains possess unique genes contributing to virulence.
      We used genomic subtractive hybridization to identify regions of genomic DNA
      unique to virulent RDP type III-3 GBS strains. Within one of these III-3-specific
      regions is a 1,506-bp open reading frame, spb1 (surface protein of group B
      streptococcus 1). A mutant type III GBS strain lacking Spb1 was constructed in
      virulent RDP type III-3 strain 874391, and the interactions of the wild-type and
      spb1 isogenic mutant with a variety of epithelial cells important to GBS
      colonization and infection were compared. While adherence of the spb1 isogenic
      mutant to A549 respiratory, C2Bbe1 colonic, and HeLa cervical epithelial cells
      was slightly lower than that of the 874391 strain, invasion of the Spb1(-) mutant
      was significantly reduced with these cell lines compared to what was seen with
      874391. The defect in epithelial invasion was corrected by supplying spb1 in
      trans. These observations suggest that Spb1 contributes to the pathogenesis of
      neonatal GBS infection by mediating internalization of virulent serotype III GBS
      and confirm that understanding of the population structure of bacteria may lead
      to insights into the pathogenesis of human infections.

PMID- 14638774
TI  - Characterization of a protective monoclonal antibody recognizing Staphylococcus
      aureus MSCRAMM protein clumping factor A.
AB  - The Staphylococcus aureus MSCRAMM (microbial surface components recognizing
      adhesive matrix molecules) protein clumping factor A (ClfA) has been shown to be
      a critical virulence factor in several experimental models of infection. This
      report describes the generation, characterization, and in vivo evaluation of a
      murine monoclonal antibody (MAb) against ClfA. Flow cytometric analysis revealed
      that MAb 12-9 recognized ClfA protein expressed by all of the clinical S. aureus
      strains obtained from a variety of sources. In assays measuring whole-cell S.
      aureus binding to human fibrinogen, MAb 12-9 inhibited S. aureus binding by over
      90% and displaced up to 35% of the previously adherent S. aureus bacteria.
      Furthermore, a single infusion of MAb 12-9 was protective against an intravenous
      challenge with a methicillin-resistant strain of S. aureus in a murine sepsis
      model (P < 0.0001). These data suggest that anti-ClfA MAb 12-9 should be further
      investigated as a novel immunotherapy for the treatment and prevention of life
      threatening S. aureus infections.

PMID- 14638775
TI  - The Mycobacterium tuberculosis complex-restricted gene cfp32 encodes an expressed
      protein that is detectable in tuberculosis patients and is positively correlated
      with pulmonary interleukin-10.
AB  - Human tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, a
      subspecies of the M. tuberculosis complex (MTC) of mycobacteria. Postgenomic
      dissection of the M. tuberculosis proteome is ongoing and critical to furthering
      our understanding of factors mediating M. tuberculosis pathobiology. Towards this
      end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growing M.
      tuberculosis (originally annotated as Rv0577 and hereafter designated CFP32) was
      identified, cloned, and characterized. The cfp32 gene is MTC restricted, and the
      gene product is expressed ex vivo as determined by the respective Southern and
      Western blot testing of an assortment of mycobacteria. Moreover, the cfp32 gene
      sequence is conserved within the MTC, as no polymorphisms were found in the
      tested cfp32 PCR products upon sequence analysis. Western blotting of M.
      tuberculosis subcellular fractions localized CFP32 predominantly to the CF and
      cytosolic compartments. Data to support the in vivo expression of CFP32 were
      provided by the serum recognition of recombinant CFP32 in 32% of TB patients by
      enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of
      CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients.
      Of greatest interest was the observation that, per sample, sputum CFP32 levels (a
      potential indicator of increasing bacterial burden) correlated with levels of
      expression in sputum of interleukin-10 (an immunosuppressive cytokine and a
      putative contributing factor to disease progression) but not levels of gamma
      interferon (a key cytokine in the protective immune response in TB), as measured
      by ELISA. Combined, these data suggest that CFP32 serves a necessary biological
      function(s) in tubercle bacilli and may contribute to the M. tuberculosis
      pathogenic mechanism. Overall, CFP32 is an attractive target for drug and vaccine
      design as well as new diagnostic strategies.

PMID- 14638776
TI  - Human antibodies specific for the high-molecular-weight adhesion proteins of
      nontypeable Haemophilus influenzae mediate opsonophagocytic activity.
AB  - The HMW1- and HMW2-like adhesion proteins of nontypeable Haemophilus influenzae
      are expressed by 75% of these strains, and antibodies directed against these
      proteins are protective in animal models of infection. The purpose of the present
      study was to define the functional activity of human antibodies specific for
      these proteins in an in vitro complement-dependent opsonophagocytic assay. Human
      promyelocytic cell line HL-60 served as the source of phagocytic cells, and a
      commercial preparation of intravenous immunoglobulin (IVIG) served as the source
      of human antibodies. High-molecular-weight (HMW) proteins were purified from four
      prototype nontypeable H. influenzae strains and used to prepare solid-phase
      affinity columns. IVIG was adsorbed on each column to remove strain-specific anti
      HMW antibodies and to allow recovery of affinity-purified anti-HMW antibody
      fractions. Unadsorbed IVIG killed each of the prototype strains at titers of 1:80
      to 1:320. HMW-adsorbed sera demonstrated fourfold decreases in opsonophagocytic
      titer against the homologous strains compared to unadsorbed IVIG. Affinity
      purified anti-HMW antibody preparations demonstrated opsonophagocytic titers of
      1:20 to 1:80 against the respective homologous strains and opsonophagocytic
      titers as high as 1:80 against heterologous strains. None of the affinity
      purified anti-HMW antibody preparations was opsonophagocytic for a representative
      nontypeable H. influenzae strain that did not express HMW1- or HMW2-like
      proteins. These data demonstrate that human antibodies specific for the HMW1/HMW2
      like adhesion proteins of nontypeable H. influenzae are opsonophagocytic and that
      such antibodies recognize epitopes shared by the HMW proteins of unrelated
      nontypeable H. influenzae strains. These results argue for continued
      investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for
      prevention of disease due to nontypeable H. influenzae.

PMID- 14638777
TI  - Identification and characterization of pptA: a gene involved in the phase
      variable expression of phosphorylcholine on pili of Neisseria meningitidis.
AB  - Pili of pathogenic Neisseria are major virulence factors associated with
      adhesion, cytotoxicity, twitching motility, autoaggregation, and DNA
      transformation. Pili are modified posttranslationally by the addition of
      phosphorylcholine. However, no genes involved in either the biosynthesis or the
      transfer of phosphorylcholine in Neisseria meningitidis have been identified. In
      this study, we identified five candidate open reading frames (ORFs) potentially
      involved in the biosynthesis or transfer of phosphorylcholine to pilin in N.
      meningitidis. Insertional mutants were constructed for each ORF in N.
      meningitidis strain C311#3 to determine their effect on phosphorylcholine
      expression. The effect of the mutant ORFs on the modification by
      phosphorylcholine was analyzed by Western analysis with phosphorylcholine
      specific monoclonal antibody TEPC-15. Analysis of the mutants showed that ORF
      NMB0415, now defined as pptA (pilin phosphorylcholine transferase A), is involved
      in the addition of phosphorylcholine to pilin in N. meningitidis. Additionally,
      the phase variation (high frequency on-off switching of expression) of
      phosphorylcholine on pilin is due to changes in a homopolymeric guanosine tract
      in pptA.

PMID- 14638779
TI  - Heterologous priming-boosting immunization of cattle with Mycobacterium
      tuberculosis 85A induces antigen-specific T-cell responses.
AB  - Heterologous priming-boosting vaccination regimens involving priming with plasmid
      DNA antigen constructs and inoculating (boosting) with the same recombinant
      antigen expressed in replication-attenuated poxviruses have recently been
      demonstrated to induce immunity, based on CD4(+)- and CD8(+)-T-cell responses,
      against several diseases in both rodents and primates. We show that similar
      priming-boosting vaccination strategies using the 85A antigen of Mycobacterium
      tuberculosis are effective in inducing antigen-specific gamma interferon
      secreting CD4(+) and CD8(+) T cells, detected by a bovine enzyme-linked
      immunospot assay, in Bos indicus cattle. T-cell responses induced by priming with
      either plasmid DNA or fowlpox virus 85A constructs were enhanced by boosting with
      modified vaccinia virus Ankara expressing the same antigen administered
      intradermally. On the basis of the data, it appears that intradermal priming was
      more effective than intramuscular delivery of the priming dose for boosting with
      the modified vaccinia virus Ankara strain in cattle. Using either fowlpox virus
      or DNA priming, there was a significant bias toward induction of CD4(+)- rather
      than CD8(+)-T-cell responses. These data illustrate the general applicability of
      priming-boosting vaccination strategies for induction of antigen-specific T-cell
      responses and suggest that the method may be useful for development of veterinary
      vaccines.

PMID- 14638778
TI  - Intestinal antilectin immunoglobulin A antibody response and immunity to
      Entamoeba dispar infection following cure of amebic liver abscess.
AB  - We followed 93 subjects with amebic liver abscess (ALA) and 963 close associate
      controls at 3-month intervals for 36 months to characterize intestinal and
      humoral antibody responses to the amebic galactose-inhibitable lectin and to
      determine whether immunity developed to Entamoeba histolytica or Entamoeba dispar
      infection following cure of ALA. We found that ALA subjects had a higher
      prevalence and level of intestinal antilectin immunoglobulin A (IgA) and serum
      anti-LC3 (cysteine-rich recombinant lectin protein) IgA and IgG antibodies, P <
      0.01 and P < 0.05, respectively, compared to controls. The intestinal antilectin
      IgA antibody response was sustained over a longer time period in ALA subjects
      (71.8% remained positive at 18 months and 52.6% at 36 months, P < 0.001 compared
      to 17.6% and 10.3% of controls, respectively). ALA subjects were highly immune to
      E. dispar infection throughout the study (0% infected at 6 and 36 months,
      compared to 6.5% and 4.9% of control subjects, respectively, P < 0.05). Upon
      entry into the study, 6.3% of ALA subjects were infected with E. histolytica; the
      incidence of new E. histolytica infections in controls (as determined by culture)
      was too low (1.4%) to determine whether ALA subjects exhibited immunity to new
      infections. We found that stool cultures every 3 months markedly underestimated
      the occurrence of new E. histolytica infections, as 15.3% of controls
      seroconverted after 12 months of follow-up. Unfortunately, under the field
      conditions present in Durban, South Africa, enzyme-linked immunosorbent assay for
      detection of lectin antigen in stool yielded unreliable results. In summary,
      subjects cured of ALA exhibited sustained mucosal IgA antibody responses to the
      amebic galactose-inhibitable lectin and a high level of immunity to E. dispar
      infection. Determination of immunity to E. histolytica following cure of ALA will
      require the use of more sensitive and reliable diagnostic methods.

PMID- 14638780
TI  - Th1-directing adjuvants increase the immunogenicity of oligosaccharide-protein
      conjugate vaccines related to Streptococcus pneumoniae type 3.
AB  - Oligosaccharide (OS)-protein conjugates are promising candidate vaccines against
      encapsulated bacteria, such as Haemophilus influenzae, Neisseria meningitidis,
      and Streptococcus pneumoniae. Although the effects of several variables such as
      OS chain length and protein carrier have been studied, little is known about the
      influence of adjuvants on the immunogenicity of OS-protein conjugates. In this
      study, a minimal protective trisaccharide epitope of Streptococcus pneumoniae
      type 3 conjugated to the cross-reacting material of diphtheria toxin was used for
      immunization of BALB/c mice in the presence of different adjuvants. Subsequently,
      half of the mice received a booster immunization with conjugate alone.
      Independent of the use and type of adjuvant, all mice produced long-lasting anti
      polysaccharide type 3 (PS3) antibody levels, which provided full protection
      against challenge with pneumococcal type 3 bacteria. All adjuvants tested
      increased the anti-PS3 antibody levels and opsonic capacities as measured by an
      enzyme-linked immunosorbent assay and an in vitro phagocytosis assay. The use of
      QuilA or a combination of the adjuvants CpG and dimethyl dioctadecyl ammonium
      bromide resulted in the highest phagocytic capacities and the highest levels of
      Th1-related immunoglobulin G (IgG) subclasses. Phagocytic capacity correlated
      strongly with Th1-associated IgG2a and IgG2b levels, to a lesser extent with Th2
      associated IgG1 levels, and weakly with thiocyanate elution as a measure of
      avidity. Thus, the improved immunogenicity of OS-protein conjugates was most
      pronounced for Th1-directing adjuvants.

PMID- 14638781
TI  - Cloning and expression of the major secreted cathepsin B-like protein from
      juvenile Fasciola hepatica and analysis of immunogenicity following liver fluke
      infection.
AB  - The functions of the cathepsin B-like proteases in liver flukes are unknown and
      analysis has been hindered by a lack of protein for study, since the protein is
      produced in small amounts by juvenile flukes. To circumvent this, we isolated and
      characterized a cDNA encoding the major secreted cathepsin B from Fasciola
      hepatica. The predicted preproprotein is 339 amino acids in length, with the
      mature protease predicted to be 254 amino acids long, and shows significant
      similarity to parasite and mammalian cathepsin B. Only one of the two conserved
      histidine residues required for cathepsin B exopeptidase activity is predicted to
      be present. Recombinant preproprotein was produced in yeast, and it was shown
      that the recombinant proprotein can undergo a degree of self-processing in vitro
      to the mature form, which is active against gelatin and synthetic peptide
      substrates. The recombinant protein is antigenic in vaccinated rats, and
      antibodies to the protein are detected early after infection of rats and sheep
      with F. hepatica. The kinetics of the response to cathepsin B and cathepsin L
      after infection of sheep and rats confirm the temporal expression of these
      proteins during the life cycle of the parasite.

PMID- 14638782
TI  - Mitogenic effect of Bartonella bacilliformis on human vascular endothelial cells
      and involvement of GroEL.
AB  - Bartonellae are bacterial pathogens for a wide variety of mammals. In humans,
      bartonellosis can result in angioproliferative lesions that are potentially life
      threatening to the patient, including bacillary angiomatosis, bacillary peliosis,
      and verruga peruana. The results of this study show that Bartonella
      bacilliformis, the agent of Oroya fever and verruga peruana, produces a
      proteinaceous mitogen for human vascular endothelial cells (HUVECs) that acts in
      a dose-dependent fashion in vitro with maximal activity at >or=72 h of exposure
      and results in a 6- to 20-fold increase in cell numbers relative to controls. The
      mitogen increases bromodeoxyuridine (BrdU) incorporation into HUVECs by almost
      twofold relative to controls. The mitogen is sensitive to heat and trypsin but is
      not affected by the lipopolysaccharide inhibitor polymyxin B. The mitogen does
      not affect caspase 3 activity in HUVECs undergoing serum starvation-induced
      apoptosis. The Bartonella mitogen was found in bacterial culture supernatants,
      the soluble cell lysate fraction, and, to a lesser degree, in insoluble cell
      fractions of the bacterium. In contrast, soluble cell lysate fractions from
      closely related B. henselae, although possessing significant mitogenicity for
      HUVECs, resulted in only about a twofold increase in cell numbers. Biochemical
      and immunological analyses identified GroEL as a participant in the observed
      HUVEC mitogenicity. A B. bacilliformis strain containing the intact groES-groEL
      operon on a multicopy plasmid was generated and used to demonstrate a correlation
      between HUVEC mitogenicity and GroEL levels in the lysate (r(2) = 0.85).
      Antiserum to GroEL significantly inhibited mitogenicity of the lysate. Data also
      show that GroEL is located in the soluble and insoluble fractions (including
      inner and outer membranes) of the cell and is actively secreted by B.
      bacilliformis.

PMID- 14638783
TI  - Temporal analysis of Borrelia burgdorferi Erp protein expression throughout the
      mammal-tick infectious cycle.
AB  - Previous immunological studies indicated that the Lyme disease spirochete,
      Borrelia burgdorferi, expresses Erp outer surface proteins during mammalian
      infection. We conducted analyses of Erp expression throughout the entire tick
      mammal infectious cycle, which revealed that the bacteria regulate Erp production
      in vivo. Bacteria within unfed nymphal ticks expressed little to no Erp proteins.
      However, as infected ticks fed on mice, B. burgdorferi increased production of
      Erp proteins, with essentially all transmitted bacteria expressing these
      proteins. Mice infected with B. burgdorferi mounted rapid IgM responses to all
      tested Erp proteins, followed by strong immunoglobulin G responses that generally
      increased in intensity throughout 11 months of infection, suggesting continued
      exposure of Erp proteins to the host immune system throughout chronic infection.
      As naive tick larvae acquired B. burgdorferi by feeding on infected mice,
      essentially all transmitted bacteria produced Erp proteins, also suggestive of
      continual Erp expression during mammalian infection. Shortly after the larvae
      acquired bacteria, Erp production was drastically downregulated. The expression
      of Erp proteins on B. burgdorferi throughout mammalian infection is consistent
      with their hypothesized function as factor H-binding proteins that protect the
      bacteria from host innate immune responses.

PMID- 14638784
TI  - Role of receptor proteins for enterobactin and 2,3-dihydroxybenzoylserine in
      virulence of Salmonella enterica.
AB  - Single, double, and triple mutants of an enterobactin-deficient mutant strain of
      Salmonella enterica serovar Typhimurium were constructed that were defective in
      the expression of the iron-regulated outer membrane proteins (IROMPs) FepA, IroN,
      and Cir, which are proposed to function as catecholate receptors. Uptake of
      naturally occurring and chemically synthesized catecholate molecules by these
      mutants was assessed in standard growth promotion assays. Unique patterns of
      uptake were identified for each IROMP; specifically, FepA and IroN were confirmed
      to be required for transport of enterobactin, and all three proteins were shown
      to function as receptors for the enterobactin breakdown product 2,3
      dihydroxybenzoylserine. The fepA, iroN, and cir alleles were transduced to
      enterobactin-proficient strains of S. enterica serovar Typhimurium and S.
      enterica serovar Enteritidis, and the resulting phenotypes were confirmed by
      analysis of outer membrane protein profiles, by sensitivity to KP-736, a
      catecholate-cephalosporin conjugate, and by growth promotion tests on egg white
      agar. Intragastric infections of mice with the S. enterica serovar Typhimurium
      strains indicated that the parental strain and the fepA iroN double mutant were
      similarly virulent but that the fepA iroN cir triple mutant was significantly
      attenuated. Moreover, in mixed infections, the fepA iroN mutant showed similar
      cecal colonization and invasion of the liver to the parental strain, while the
      triple mutant showed significantly reduced cecal colonization and no measurable
      spread to the liver. Infections of 4-day-old chicks with S. enterica serovar
      Enteritidis strains also indicated that mutation of the fepA iroN genes did not
      significantly reduce cecal colonization and systemic spread compared with those
      of the parental strain. The results indicate that, while enterobactin uptake is
      not essential for the virulence of S. enterica serovars in mouse and chicken
      infection models, the ability to take up 2,3-dihydroxybenzoylserine via any of
      the three catecholate siderophore receptors appears to play an important role,
      since the S. enterica serovar Typhimurium triple mutant was significantly
      attenuated in the mouse model. Salmochelins appear not to be involved in the
      virulence of S. enterica.

PMID- 14638785
TI  - Functional analysis of the Mycobacterium tuberculosis MprAB two-component signal
      transduction system.
AB  - The mechanisms utilized by Mycobacterium tuberculosis to establish, maintain, or
      reactivate from latent infection in the host are largely unknown but likely
      include genes that mediate adaptation to conditions encountered during
      persistence. Previously, a two-component signal transduction system, mprAB, was
      found to be required in M. tuberculosis for establishment and maintenance of
      persistent infection in a tissue- and stage-specific fashion. To begin to
      characterize the role of this system in M. tuberculosis physiology and virulence,
      a functional analysis of the mprA and mprB gene products was initiated. Here,
      evidence is presented demonstrating that sensor kinase MprB and response
      regulator MprA function as an intact signal-transducing pair in vitro and in
      vivo. Sensor kinase MprB can be autophosphorylated, can donate phosphate to MprA,
      and can act as a phospho-MprA phosphatase in vitro. Correspondingly, response
      regulator MprA can accept phosphate from MprB or from small phosphodonors
      including acetyl phosphate. Mutagenesis of residues His249 in MprB and Asp48 in
      MprA abolished the ability of these proteins to be phosphorylated in vitro.
      Introduction of these alleles into Mycobacterium bovis BCG attenuated virulence
      in macrophages in vivo. Together, these results support a role for the mprAB two
      component system in M. tuberculosis physiology and pathogenesis. Characterization
      of two-component signal transduction systems will enhance our understanding of
      processes regulated by M. tuberculosis during acute and/or persistent infection
      in the host.

PMID- 14638786
TI  - A humoral immune response confers protection against Haemophilus ducreyi
      infection.
AB  - Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital
      ulcer disease chancroid. Neither naturally occurring chancroid nor experimental
      infection with H. ducreyi results in protective immunity. Likewise, a single
      inoculation of H. ducreyi does not protect pigs against subsequent infection.
      Accordingly, we used the swine model of chancroid infection to examine the impact
      of multiple inoculations on a host's immune response. After three successive
      inoculations with H. ducreyi, pigs developed a modestly protective immune
      response evidenced by the decreased recovery of viable bacteria from lesions. All
      lesions biopsied 2 days after the first and second inoculations contained viable
      H. ducreyi cells, yet only 55% of the lesions biopsied 2 days after the third
      inoculation did. Nearly 90% of the lesions biopsied 7 days after the first
      inoculation contained viable H. ducreyi cells, but this percentage dropped to
      only 16% after the third inoculation. Between the first and third inoculations,
      the average recovery of CFU from lesions decreased approximately 100-fold. The
      reduced recovery of bacteria corresponded directly with a fivefold increase in H.
      ducreyi-specific antibody titers and the emergence of bactericidal activity.
      These immune sera were protective when administered to naive pigs prior to
      challenge with H. ducreyi. These data suggest that pigs mount an effective
      humoral immune response to H. ducreyi after multiple exposures to the organism.

PMID- 14638787
TI  - Synergism of gamma interferon and interleukin-5 in the control of murine
      filariasis.
AB  - There has been a prevailing perception that Th1 and Th2 immune responses induce
      antagonistic immune effector mechanisms during an infection. We investigated the
      role of the Th1 cytokine gamma interferon (IFN-gamma) and the Th2 cytokine
      interleukin-5 (IL-5) in murine filariasis infections with the rodent filarial
      nematode Litomosoides sigmodontis with regard to immune responses to the
      parasite. Earlier data showed an important role for IL-5 and IFN-gamma in
      effective immune responses to filarial infection. Therefore, in this study it was
      asked whether IL-5 and IFN-gamma act synergistically or antagonistically. Indeed,
      IL-5 as well as IFN-gamma knockout (KO) mice show a higher worm load than the
      wild-type controls. IFN-gamma/IL-5 double-KO mice had a significantly higher worm
      load than any of the single-KO mice, suggesting a synergism between IFN-gamma and
      IL-5 in controlling worm infection. Neutrophils are known to play an important
      role for the containment and encapsulation process of the worms. In infected IFN
      gamma KO, IL-5 KO, and IFN-gamma/IL-5 double-KO mice, neutrophils were
      significantly reduced in chemotactic activity levels compared to controls. In
      addition, the level of phagocytosis activity of neutrophils from IFN-gamma/IL-5
      double-KO mice was further decreased in comparison to that of the single-KO mice.
      Levels of tumor necrosis factor alpha, which is an important factor for
      neutrophil activation, were found to be reduced in macrophages from KO mice. In
      conclusion, these results argue for immune effector mechanisms in murine filarial
      infection that are dependent on both IFN-gamma and IL-5. Synergistic effects of
      the two cytokines may be mediated, at least in part, by neutrophils for the
      control of adult worms.

PMID- 14638788
TI  - Removal of Wolbachia from Brugia pahangi is closely linked to worm death and
      fecundity but does not result in altered lymphatic lesion formation in Mongolian
      gerbils (Meriones unguiculatus).
AB  - Approximately 30 years ago, researchers reported intracellular bacteria in
      filarial nematodes. These bacteria are relatives of the arthropod symbiont
      Wolbachia and occur in many filarial nematodes, including Brugia pahangi and
      Brugia malayi. Wolbachia bacteria have been implicated in a variety of roles,
      including filaria development and fecundity and the pathogenesis of lymphatic
      lesions associated with filarial infections. However, the role of the bacteria in
      worm biology or filarial disease is still not clear. The present experiments
      support previous data showing that tetracycline eliminates or reduces Wolbachia
      bacteria in B. pahangi in vivo. The elimination of Wolbachia was closely linked
      to a reduction in female fecundity and the viability of both sexes, suggesting
      that the killing of Wolbachia is detrimental to B. pahangi. The gerbils treated
      with tetracycline showed reduced levels of interleukin-4 (IL-4) and IL-5 mRNA in
      renal lymph nodes and spleens compared with the levels in B. pahangi-infected
      gerbils not treated with tetracycline. However, similar findings were noted in B.
      pahangi-infected gerbils treated with ivermectin, suggesting that the loss of
      circulating microfilariae, not the reduction of Wolbachia bacteria, was
      associated with the altered cytokine profile. Despite the change in T-cell
      cytokines, there was no difference in the sizes of renal lymph nodes isolated
      from gerbils in each treatment group. Furthermore, the numbers, sizes, or
      cellular compositions of granulomas examined in the lymphatics or renal lymph
      nodes did not differ with treatment. These data suggest that Wolbachia may not
      play a primary role in the formation of lymphatic lesions in gerbils chronically
      infected with B. pahangi.

PMID- 14638789
TI  - Monoclonal antibody MG96 completely blocks Plasmodium yoelii development in
      Anopheles stephensi.
AB  - In spite of research efforts to develop vaccines against the causative agent of
      human malaria, Plasmodium falciparum, effective control remains elusive. The
      predominant vaccine strategy focuses on targeting parasite blood stages in the
      vertebrate host. An alternative approach has been the development of transmission
      blocking vaccines (TBVs). TBVs target antigens on parasite sexual stages that
      persist within the insect vector, anopheline mosquitoes, or target mosquito
      midgut proteins that are presumed to mediate parasite development. By blocking
      parasite development within the insect vector, TBVs effectively disrupt
      transmission and the resultant cascade of secondary infections. Using a mosquito
      midgut-specific mouse monoclonal antibody (MG96), we have partially characterized
      membrane-bound midgut glycoproteins in Anopheles gambiae and Anopheles stephensi.
      These proteins are present on the microvilli of midgut epithelial cells in both
      blood-fed and unfed mosquitoes, suggesting that the expression of the protein is
      not induced as a result of blood feeding. MG96 exhibits a dose-dependent blocking
      effect against Plasmodium yoelii development in An. stephensi. We achieved 100%
      blocking of parasite development in the mosquito midgut. Preliminary
      deglycosylation assays indicate that the epitope recognized by MG96 is a complex
      oligosaccharide. Future investigation of the carbohydrate epitope as well as gene
      identification should provide valuable insight into the possible mechanisms of
      ookinete attachment and invasion of mosquito midgut epithelial cells.

PMID- 14638790
TI  - Analysis of virulence and inflammatory potential of Shigella flexneri purine
      biosynthesis mutants.
AB  - Several Shigella flexneri mutants with defects in aromatic amino acid and/or
      purine biosynthesis have been evaluated as vaccines in humans or in animal
      models. To be suitable as a vaccine, a mutant has to show virulence attenuation,
      minimal reactogenicity, and a good immunogenic potential in animal models. With
      this aim, we have constructed five S. flexneri 5 (wild-type strain M90T) mutants
      with inactivation of one or two of the loci purEK, purHD, and guaBA, governing
      early or late steps of purine biosynthesis. The mutants have been analyzed in
      vitro in cell cultures and in vivo in the Sereny test and in the murine pulmonary
      model of shigellosis. M90T guaBA, M90T guaBA purEK, M90T guaBA purHD, and M90T
      purHD purEK gave a negative result in the Sereny test. In contrast, in the murine
      pulmonary model all of the strains had the same 50% lethal dose as the wild type,
      except M90T guaBA purHD, which did not result in death of the animals.
      Nevertheless, bacterial counts in infected lungs, immunohistochemistry, and
      reverse transcription-PCR analysis of mRNAs for tumor necrosis factor alpha (TNF
      alpha), gamma interferon (IFN-gamma), interleukin-1beta (IL-1beta), IL-6, IL-12,
      and inducible nitric oxide synthase (iNOS) revealed significant differences among
      the strains. At 72 h postinfection, M90T guaBA purHD still induced
      proinflammatory cytokines and factors such as IL-1beta, IL-6, TNF-alpha, and
      iNOS, along with cytokines such as IL-12 and IFN-gamma. Moreover, in the absence
      of evident lesions in murine tissues, this mutant highly stimulated major
      histocompatibility complex class II expression, showing a significant ability to
      activate the innate immunity of the host.

PMID- 14638791
TI  - Orally administered CpG oligodeoxynucleotide induces production of CXC and CC
      chemokines in the gastric mucosa and suppresses bacterial colonization in a mouse
      model of Helicobacter pylori infection.
AB  - Bacterial DNA and unmethylated CpG oligodeoxynucleotides (CpG ODN) are known to
      be potent stimulators of the innate immune system in vitro and in vivo. We
      therefore investigated if oral administration of CpG ODN could enhance innate
      immunity in the gastric mucosa and control the extent of Helicobacter pylori
      infection in mice. Intragastric administration of a single dose of CpG ODN
      significantly increased local production of the CC chemokines macrophage
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES and the CXC
      chemokine gamma interferon-inducible protein 10 in the stomach and/or the small
      intestine. Importantly, intragastric administration of CpG ODN to mice with an
      already established H. pylori infection, in the absence of any coadministered
      antigen, was found to reduce the bacterial load in the stomach compared to the
      load in H. pylori-infected control mice, while similar administration of non-CpG
      ODN had no effect on the bacterial load. The reduction in the bacterial numbers
      in the stomachs of mice treated with CpG ODN was associated with enhanced
      infiltration of immune cells and increased RANTES production in the gastric
      mucosa compared to the infiltration of immune cells and RANTES production in H.
      pylori-infected control animals. These findings suggest that intragastric
      administration of CpG ODN without antigen codelivery may represent a valuable
      strategy for induction of innate immunity against H. pylori infection.

PMID- 14638792
TI  - In situ study of abundant expression of proinflammatory chemokines and cytokines
      in pulmonary granulomas that develop in cynomolgus macaques experimentally
      infected with Mycobacterium tuberculosis.
AB  - Tuberculosis remains a major public health problem worldwide. Chemokines and
      cytokines organize and direct infiltrating cells to sites of infection, and these
      molecules likely play crucial roles in granuloma formation and maintenance. To
      address this issue, we used in situ hybridization (ISH) to measure chemokine and
      cytokine mRNA expression levels and patterns directly in lung tissues from
      cynomolgus macaques (Macaca fascicularis) experimentally infected with a low dose
      of virulent Mycobacterium tuberculosis. We examined more than 300 granulomas and
      observed abundant expression of gamma interferon (IFN-gamma)-inducible chemokine
      mRNAs (CXCL9/monokine induced by IFN-gamma, CXCL10/IFN-gamma-inducible protein,
      and CXCL11/IFN-gamma-inducible T-cell alpha-chemoattractant) within solid and
      caseous granulomas, and there was only minimal expression in nongranulomatous
      regions of tissue. The mRNA expression patterns of IFN-gamma and tumor necrosis
      factor alpha were examined in parallel, and the results revealed that cytokine
      mRNA(+) cells were abundant and generally localized to the granulomas.
      Mycobacterial 16S rRNA expression was also measured by ISH, and the results
      revealed that there was localization predominantly to the granulomas and that the
      highest signal intensity was in caseous granulomas. We observed several
      granulomatous lesions with exceptionally high levels of RNA for mycobacterial 16S
      rRNA, IFN-gamma, and IFN-gamma-inducible chemokines, suggesting that the local
      presence of mycobacteria is partially responsible for the upregulation of IFN
      gamma-inducible chemokines and recruitment of CXCR3(+) cells, which were also
      abundant in granulomatous lesions. These results suggest that expression of CXCR3
      ligands and the subsequent recruitment of CXCR3(+) cells are involved in
      granuloma formation and maintenance.

PMID- 14638793
TI  - Effect of Mycobacterium bovis BCG vaccination on Mycobacterium-specific cellular
      proliferation and tumor necrosis factor alpha production from distinct guinea pig
      leukocyte populations.
AB  - In this study, we focused on three leukocyte-rich guinea pig cell populations,
      bronchoalveolar lavage (BAL) cells, resident peritoneal cells (PC), and
      splenocytes (SPC). BAL cells, SPC, and PC were stimulated either with live
      attenuated Mycobacterium tuberculosis H37Ra or with live or heat-killed virulent
      M. tuberculosis H37Rv (multiplicity of infection of 1:100). Each cell population
      was determined to proliferate in response to heat-killed virulent H37Rv, whereas
      no measurable proliferative response could be detected upon stimulation with live
      mycobacteria. Additionally, this proliferative capacity (in SPC and PC
      populations) was significantly enhanced upon prior vaccination with Mycobacterium
      bovis BCG. Accordingly, in a parallel set of experiments we found a strong
      positive correlation between production of antigen-specific bioactive tumor
      necrosis factor alpha (TNF-alpha) and prior vaccination with BCG. A nonspecific
      stimulus, lipopolysaccharide, failed to induce this effect on BAL cells, SPC, and
      PC. These results showed that production of bioactive TNF-alpha from
      mycobacterium-stimulated guinea pig cell cultures positively correlates with the
      vaccination status of the host and with the virulence of the mycobacterial
      strain.

PMID- 14638794
TI  - Characterization of an extracellular virulence factor made by group A
      Streptococcus with homology to the Listeria monocytogenes internalin family of
      proteins.
AB  - Leucine-rich repeats (LRR) characterize a diverse array of proteins and function
      to provide a versatile framework for protein-protein interactions. Importantly,
      each of the bacterial LRR proteins that have been well described, including those
      of Listeria monocytogenes, Yersinia pestis, and Shigella flexneri, have been
      implicated in virulence. Here we describe an 87.4-kDa group A Streptococcus (GAS)
      protein (designated Slr, for streptococcal leucine-rich) containing 10 1/2
      sequential units of a 22-amino-acid C-terminal LRR homologous to the LRR of the
      L. monocytogenes internalin family of proteins. In addition to the LRR domain,
      slr encodes a gram-positive signal secretion sequence characteristic of a
      lipoprotein and a putative N-terminal domain with a repeated histidine triad
      motif (HxxHxH). Real-time reverse transcriptase PCR assays indicated that slr is
      transcribed abundantly in vitro in the exponential phase of growth. Flow
      cytometry confirmed that Slr was attached to the GAS cell surface. Western
      immunoblot analysis of sera obtained from 80 patients with invasive infections,
      noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated
      that Slr is produced in vivo. An isogenic mutant strain lacking slr was
      significantly less virulent in an intraperitoneal mouse model of GAS infection
      and was significantly more susceptible to phagocytosis by human polymorphonuclear
      leukocytes. These studies characterize the first GAS LRR protein as an
      extracellular virulence factor that contributes to pathogenesis and may
      participate in evasion of the innate host defense.

PMID- 14638796
TI  - Beta-1,2- and alpha-1,2-linked oligomannosides mediate adherence of Candida
      albicans blastospores to human enterocytes in vitro.
AB  - Candida albicans is a commensal dimorphic yeast of the digestive tract that
      causes hematogenously disseminated infections in immunocompromised individuals.
      Endogenous invasive candidiasis develops from C. albicans adhering to the
      intestinal epithelium. Adherence is mediated by the cell wall surface, a domain
      composed essentially of mannopyranosyl residues bound to proteins, the N-linked
      moiety of which comprises sequences of alpha-1,2- and beta-1,2-linked mannose
      residues. Beta-1,2-linked mannosides are also associated with a glycolipid,
      phospholipomannan, at the C. albicans surface. In order to determine the roles of
      beta-1,2 and alpha-1,2 oligomannosides in the C. albicans-enterocyte interaction,
      we developed a model of adhesion of C. albicans VW32 blastospores to the apical
      regions of differentiated Caco-2 cells. Preincubation of yeasts with monoclonal
      antibodies (MAbs) specific for alpha-1,2 and beta-1,2 mannan epitopes resulted in
      a dose-dependent decrease in adhesion (50% of the control with a 60- micro g/ml
      MAb concentration). In competitive assays beta-1,2 and alpha-1,2 tetramannosides
      were the most potent carbohydrate inhibitors, with 50% inhibitory concentrations
      of 2.58 and 6.99 mM, respectively. Immunolocalization on infected monolayers with
      MAbs specific for alpha-1,2 and beta-1,2 oligomannosides showed that these
      epitopes were shed from the yeast to the enterocyte surface. Taken together, our
      data indicate that alpha-1,2 and beta-1,2 oligomannosides are involved in the C.
      albicans-enterocyte interaction and participate in the adhesion of the yeasts to
      the mucosal surface.

PMID- 14638795
TI  - Attenuated signature-tagged mutagenesis mutants of Brucella melitensis identified
      during the acute phase of infection in mice.
AB  - For this study, we screened 1,152 signature-tagged mutagenesis mutants of
      Brucella melitensis 16M in a mouse model of infection and found 36 of them to be
      attenuated in vivo. Molecular characterization of transposon insertion sites
      showed that for four mutants, the affected genes were only present in
      Rhizobiaceae. Another mutant contained a disruption in a gene homologous to mosA,
      which is involved in rhizopine biosynthesis in some strains of Rhizobium,
      suggesting that this sugar may be involved in Brucella pathogenicity. A mutant
      was disrupted in a gene homologous to fliF, a gene potentially coding for the MS
      ring, a basal component of the flagellar system. Surprisingly, a mutant was
      affected in the rpoA gene, coding for the essential alpha-subunit of the RNA
      polymerase. This disruption leaves a partially functional protein, impaired for
      the activation of virB transcription, as demonstrated by the absence of induction
      of the virB promoter in the Tn5::rpoA background. The results presented here
      highlight the fact that the ability of Brucella to induce pathogenesis shares
      similarities with the molecular mechanisms used by both Rhizobium and
      Agrobacterium to colonize their hosts.

PMID- 14638797
TI  - Disruption of cell polarity by enteropathogenic Escherichia coli enables
      basolateral membrane proteins to migrate apically and to potentiate physiological
      consequences.
AB  - Enteropathogenic Escherichia coli (EPEC) disrupts the structure and barrier
      function of host intestinal epithelial tight junctions (TJs). The impact of EPEC
      on TJ "fence function," i.e., maintenance of cell polarity, has not been
      investigated. In polarized cells, proteins such as beta(1)-integrin and
      Na(+)/K(+) ATPase are restricted to basolateral (BL) membranes. The outer
      membrane EPEC protein intimin possesses binding sites for the EPEC translocated
      intimin receptor (Tir) and beta(1)-integrin. Restriction of beta(1)-integrin to
      BL domains, however, precludes opportunity for interaction. We hypothesize that
      EPEC perturbs TJ fence function and frees BL proteins such as beta(1)-integrin to
      migrate to apical (AP) membranes of host cells, thus allowing interactions with
      bacterial adhesins such as intimin. The aim of this study was to determine
      whether EPEC alters the polar distribution of BL proteins, in particular beta(1)
      integrin, and if such redistribution contributes to pathogenesis. Human
      intestinal epithelial T84 cells and EPEC strain E2348/69 were used. Selective
      biotinylation of AP or BL membrane proteins and confocal microscopy showed the
      presence of beta(1)-integrin and Na(+)/K(+) ATPase on the AP membrane following
      infection. beta(1)-Integrin antibody afforded no protection against the initial
      EPEC-induced decrease in transepithelial electrical resistance (TER) but halted
      the progressive decrease at later time points. While the effects of EPEC on TJ
      barrier and fence function were Tir dependent, disruption of cell polarity by
      calcium chelation allowed a tir mutant to be nearly as effective as wild-type
      EPEC. In contrast, deletion of espD, which renders the type III secretory system
      ineffective, had no effect on TER even after calcium chelation, suggesting that
      the putative beta(1)-integrin-intimin interaction serves to provide intimate
      contact, like that of Tir and intimin, making translocation of effector molecules
      more efficient. We conclude that the initial alterations of TJ barrier and fence
      function by EPEC are Tir dependent but that later disruption of cell polarity and
      accessibility of EPEC to BL membrane proteins, such as beta(1)-integrin,
      potentiates the physiological perturbations.

PMID- 14638798
TI  - Prophage induction and expression of prophage-encoded virulence factors in group
      A Streptococcus serotype M3 strain MGAS315.
AB  - The genome of the highly virulent group A Streptococcus (GAS) serotype M3 strain
      MGAS315 has six prophages that encode six proven or putative virulence factors.
      We examined prophage induction and expression of prophage-encoded virulence
      factors by this strain under in vitro conditions inferred to approximate in vivo
      conditions. Coculture of strain MGAS315 with Detroit 562 (D562) human epithelial
      pharyngeal cells induced the prophage encoding streptococcal pyrogenic exotoxin K
      (SpeK) and extracellular phospholipase A(2) (Sla) and the prophage encoding
      streptodornase (Sdn). Increased gene copy numbers after induction correlated with
      increased speK, sla, and sdn transcript levels. Although speK and sla are located
      contiguously in prophage Phi315.4, these genes were transcribed independently.
      Whereas production of immunoreactive SpeK was either absent or minimal during
      coculture of GAS with D562 cells, production of immunoreactive Sla increased
      substantially. In contrast, despite a lack of induction of the prophage encoding
      speA during coculture of GAS with D562 cells, the speA transcript level and
      production of immunoreactive streptococcal pyrogenic exotoxin A (SpeA) increased.
      Exposure of strain MGAS315 to hydrogen peroxide, an oxidative stressor, induced
      the prophage encoding mitogenic factor 4 (MF4), and there was a concomitant
      increase in the mf4 transcript. All prophages of strain MGAS315 that encode
      virulence factors were induced during culture with mitomycin C, a DNA-damaging
      agent. However, the virulence factor gene transcript levels and production of the
      encoded proteins decreased after mitomycin C treatment. Taken together, the
      results indicate that a complex relationship exists among environmental culture
      conditions, prophage induction, and production of prophage-encoded virulence
      factors.

PMID- 14638799
TI  - Infection and inflammation in skeletal muscle from nonhuman primates infected
      with different genospecies of the Lyme disease spirochete Borrelia burgdorferi.
AB  - Lyme borreliosis is a multisystemic disease caused by various genospecies of the
      spirochete Borrelia burgdorferi. To investigate muscle involvement in the
      nonhuman primate (NHP) model of Lyme disease, 16 adult Macaca mulatta animals
      inoculated with strain N40 of B. burgdorferi sensu strictu by syringe or by tick
      bite or with strain Pbi of B. burgdorferi genospecies garinii by syringe were
      studied. Animals were necropsied while immunosuppressed on day 50 (two animals
      each inoculated with B. burgdorferi N40 by syringe and with B. garinii Pbi by
      syringe) or on day 90, 40 days after immunosuppression had been discontinued
      (four animals each inoculated with strain N40 by syringe, with strain N40 by tick
      bite, and with strain Pbi by syringe). Skeletal muscles removed at necropsy were
      studied by (i) microscopic examination of hematoxylin-eosin-stained sections for
      inflammation and tissue injury; (ii) immunohistochemical and digital image
      analyses for antibody and complement deposition and cellular inflammation; (iii)
      Western blot densitometry for the presence of antibodies; and (iv) reverse
      transcription-PCR for measurement of the spirochetal load or C1q (the first
      component of the complement cascade) synthesis. The results showed that N40 was
      more infectious for NHPs than Pbi. NHPs inoculated with N40 but not with Pbi
      developed myositis. The inflammation in skeletal muscle was more severe in NHPs
      inoculated with N40 by syringe than in those inoculated by tick bite. The
      predominant cells in the inflammatory infiltrate were T cells and plasma cells.
      The deposition of antibody and complement in inflamed muscles from N40-inoculated
      NHPs was significantly higher than that in Pbi-inoculated NHPs. The spirochetal
      load was very high in the two N40-inoculated NHPs examined while they were
      immunosuppressed but decreased to minimal levels in the NHPs when
      immunocompetence was restored. We conclude that myositis can be a prominent
      feature of Lyme borreliosis depending on the infecting organism and host immune
      status.

PMID- 14638800
TI  - Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with
      failed immunity.
AB  - Protective immunity against pulmonary tuberculosis (TB) is characterized by the
      formation in the lungs of granulomas consisting of macrophages and activated T
      cells producing tumor necrosis factor alpha and gamma interferon, both required
      for the activation of the phagocytes. In 90% of immunocompetent humans, this
      response controls the infection. To understand why immunity fails in the other
      10%, we studied the lungs of six patients who underwent surgery for incurable TB.
      Histologic examination of different lung lesions revealed heterogeneous
      morphology and distribution of acid-fast bacilli; only at the surface of
      cavities, i.e., in granulomas with a patent connection to the airways, were there
      numerous bacilli. The mutation profile of the isolates suggested that a single
      founder strain of Mycobacterium tuberculosis may undergo genetic changes during
      treatment, leading to acquisition of additional drug resistance independently in
      discrete physical locales. Additional drug resistance was preferentially observed
      at the cavity surface. Cytokine gene expression revealed that failure to control
      the bacilli was not associated with a generalized suppression of cellular
      immunity, since cytokine mRNA was up regulated in all lesions tested. Rather, a
      selective absence of CD4(+) and CD8(+) T cells was noted at the luminal surface
      of the cavity, preventing direct T-cell-macrophage interactions at this site,
      probably allowing luminal phagocytes to remain permissive for bacillary growth.
      In contrast, in the perinecrotic zone of the granulomas, the two cell types
      colocalized and bacillary numbers were substantially lower, suggesting that in
      this microenvironment an efficient bacteriostatic or bactericidal phagocyte
      population was generated.

PMID- 14638801
TI  - Phenotypic switching and mating type switching of Candida glabrata at sites of
      colonization.
AB  - Candida glabrata switches spontaneously at high frequency among the following
      four graded phenotypes discriminated on agar containing 1 mM CuSO(4): white,
      light brown, dark brown (DB), and very dark brown. C. glabrata also contains
      three mating type loci with a configuration similar to that of the Saccharomyces
      cerevisiae mating type cassette system, suggesting it may also undergo cassette
      switching at the expression locus MTL1. To analyze both reversible, high
      frequency phenotypic switching and mating type switching at sites of
      colonization, primary samples from the oral cavities and vaginal canals of three
      patients suffering from C. glabrata vaginitis were clonally plated on agar
      containing CuSO(4). It was demonstrated that (i) in each vaginitis patient, there
      was only one colonizing strain; (ii) an individual could have vaginal
      colonization without oral colonization; (iii) phenotypic switching occurred at
      sites of colonization; (iv) the DB phenotype predominated at the site of
      infection in all three patients; (v) genetically unrelated strains switched in
      similar, but not identical, fashions and caused vaginal infection; (vi) different
      switch phenotypes of the same strain could simultaneously dominate different body
      locations in the same host; (vii) pathogenesis could be caused by cells in
      different mating type classes; and (viii) mating type switching demonstrated at
      both the genetic and transcription levels occurred in one host.

PMID- 14638802
TI  - Recruitment of complement factor H-like protein 1 promotes intracellular invasion
      by group A streptococci.
AB  - Numerous microbial pathogens exploit complement regulatory proteins such as
      factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an
      FHL-1 and FH binding protein expressed on the surface of the human pathogenic
      bacterium, Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft
      tissue infections. In the present study, we demonstrate that Fba and FHL-1 work
      in concert to promote invasion of epithelial cells by S. pyogenes. Fba fragments
      were expressed as recombinant proteins and assayed for binding of FHL-1 and FH by
      Western blotting, enzyme-linked immunosorbent assay, and surface plasmon
      resonance. A binding site for FHL-1 and FH was localized to the N-terminal half
      of Fba, a region predicted to contain a coiled-coil domain. Deletion of this
      coiled-coil domain greatly reduced FHL-1 and FH binding. PepSpot analyses
      identified a 16-amino-acid segment of Fba which overlaps the coiled-coil domain
      that binds both FHL-1 and FH. To localize the Fba binding site in FHL-1 and FH,
      surface plasmon resonance was used to assess the interactions between the
      streptococcal protein and a series of recombinant FH deletion constructs. The Fba
      binding site was localized to short consensus repeat 7 (SCR 7), a domain common
      to FHL-1 and FH. SCR 7 contains a heparin binding site, and heparin was found to
      inhibit FHL-1 binding to Fba. FHL-1 promoted entry of Fba(+) group A streptococci
      into epithelial cells in a dose-dependent manner but did not affect invasion by
      an isogenic fba mutant. To our knowledge, this is the first report of a bacterial
      pathogen exploiting a soluble complement regulatory protein for entry into host
      cells.

PMID- 14638803
TI  - Critical roles for stx2, eae, and tir in enterohemorrhagic Escherichia coli
      induced diarrhea and intestinal inflammation in infant rabbits.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is a group of food-borne pathogens that
      can cause diarrhea, colitis, and the hemolytic uremic syndrome (HUS). The
      importance of several of the proposed EHEC virulence factors lacks experimental
      verification in animal models. The limitations of current animal models led us to
      reexamine the infant rabbit model for the study of EHEC pathogenicity. Here, we
      report that intragastric inoculation of a Shiga toxin 2 (Stx2)-producing E. coli
      O157:H7 clinical isolate into infant rabbits led to severe diarrhea and
      intestinal inflammation but no signs of HUS. We constructed a set of isogenic
      derivatives of this isolate with deletions in several putative virulence genes,
      including stx(2), eae, tir, and ehxA, to investigate the contribution of
      individual virulence factors to EHEC pathogenicity. stx(2) increased the severity
      and duration of EHEC-induced diarrhea. Furthermore, although stx(2) had no role
      in EHEC intestinal colonization nor was it required for EHEC-induced
      inflammation, stx(2) altered how the host responded to EHEC infection by
      promoting heterophilic infiltration of the colonic epithelium and lamina propria.
      Intragastric inoculation of purified Stx2 also induced inflammation and diarrhea
      in this model. Diarrhea and intestinal inflammation were also dependent on EHEC
      colonization, as EHEC derivatives with deletions in eae and tir did not colonize,
      form attaching and effacing lesions, or develop clinical signs of disease. Our
      studies indicate that infant rabbits are a useful model for investigation of the
      intestinal stage of EHEC pathogenesis and suggest that Shiga toxin may play a
      critical role in causing diarrhea and inflammation in patients infected with
      EHEC.

PMID- 14638805
TI  - Role for complement in development of Helicobacter-induced gastritis in
      interleukin-10-deficient mice.
AB  - The mechanisms by which the immune response can eradicate gastric Helicobacter
      infection are unknown. We hypothesized that Helicobacter-induced activation of
      the complement system could promote both inflammation and eradication of
      Helicobacter from the stomach. In vitro studies demonstrated that Helicobacter
      felis activates complement in normal mouse serum but not in serum from Rag2(-/-)
      mice, indicating that H. felis activates complement through the classical
      pathway. Next, we infected complement-depleted wild-type control and interleukin
      10-deficient (IL-10(-/-)) mice with H. felis. Helicobacter infection of wild-type
      mice elicited a mild, focal gastritis and did not alter serum complement levels.
      Infection of IL-10(-/-) mice with H. felis elicited severe gastritis. After the
      initial colonization, the IL-10(-/-) mice completely cleared Helicobacter from
      the stomach by day 8. In contrast to wild-type mice, H. felis-infected IL-10(-/-)
      mice had a marked increase in serum complement levels. Complement depletion of
      wild-type mice did not affect the intensity of gastric inflammation or the extent
      of Helicobacter colonization compared to that for the wild-type control mice. In
      contrast, complement depletion of Helicobacter-infected IL-10(-/-) mice decreased
      the severity of gastritis, decreased the Helicobacter-induced infiltration of
      neutrophils into the stomach, and delayed the clearance of bacteria. In vitro
      studies of stimulated splenocytes and neutrophils from IL-10(-/-) mice produced a
      twofold increase in complement production compared to that for wild-type mice.
      Pretreatment with IL-10 inhibited this increase. These studies identify a role
      for complement in the local immune response to gastric Helicobacter in IL-10(-/-)
      mice and suggest a role for IL-10 in the regulation of complement production.

PMID- 14638806
TI  - Pneumococcal surface protein A is expressed in vivo, and antibodies to PspA are
      effective for therapy in a murine model of pneumococcal sepsis.
AB  - Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the
      surface of all strains of Streptococcus pneumoniae (pneumococcus) and induces
      antibodies which protect against invasive infection in mice. Pneumococci used for
      infectious challenge in protection studies are typically collected from cultures
      grown in semisynthetic medium in vitro. The purpose of these studies is to
      confirm that PspA is expressed by pneumococci during growth in vivo at a level
      sufficient for antibodies to PspA to be protective. Mice were actively immunized
      with purified PspA or by passive transfer of monoclonal antibody (MAb) and
      challenged with a capsular type 3 strain in diluted whole blood from bacteremic
      mice. All were protected against challenge with 10 times the 50% lethal dose
      (LD(50)), and mice challenged with 1,000 times the LD(50) had increased survival
      compared with controls. Additionally, nonimmune mice treated with MAbs to PspA or
      PspA immune serum at 6 and 12 h after infection with 10 times the LD(50) also
      showed increased survival. Northern blot analysis of RNA from pneumococci grown
      either in vitro or in vivo showed similar levels of PspA mRNA. These results
      demonstrate that PspA is expressed in vivo in a mouse model and that immunization
      with PspA induces antibodies to an antigen which is expressed during the course
      of invasive infection. Immunotherapy with antibodies to PspA may have some
      utility in treating pneumococcal infections in humans.

PMID- 14638808
TI  - Interleukin-10 and pathogenesis of murine ocular toxoplasmosis.
AB  - To understand the role of interleukin-10 (IL-10) in ocular toxoplasmosis, we
      compared C57BL/6 (B6) and BALB/c background mice lacking a functional IL-10 gene
      (IL-10(-/-)) and B6 transgenic mice expressing IL-10 under the control of the IL
      2 promoter. Increased cellular infiltration and necrosis were observed in the eye
      tissue of IL-10(-/-) mice of both the B6 and BALB/c backgrounds with associated
      changes in the levels of cytokines in serum. In contrast, there was no evidence
      of necrosis in the eye tissue from IL-10 transgenic mice following parasite
      exposure. Our results demonstrate that IL-10 is important in the regulation of
      inflammation during acute ocular toxoplasmosis.

PMID- 14638807
TI  - Comparative analysis of Salmonella enterica serovar Typhimurium biofilm formation
      on gallstones and on glass.
AB  - In this study, the roles of global regulators, motility, lipopolysaccharide, and
      exopolysaccharides were further characterized with respect to biofilm formation
      on both gallstones and glass surfaces. These studies show the complex nature of
      biofilms and demonstrate that characteristics observed for each biofilm are
      unique to the particular culture condition.

PMID- 14638809
TI  - The Siderophore receptor IroN of extraintestinal pathogenic Escherichia coli is a
      potential vaccine candidate.
AB  - It would be medically and economically desirable to prevent the millions of
      annual extraintestinal infections and the thousands of associated deaths due to
      Escherichia coli. Outer membrane proteins are potential vaccine candidates for
      the prevention of these infections. This study tested the hypotheses that the
      siderophore receptor IroN is antigenic and that an IroN-specific antibody
      response confers protection in vivo. Subcutaneous immunization with denatured
      IroN resulted in a significant IroN immunoglobulin G (IgG)-specific response in
      serum (P < 0.0001) but not a systemic or mucosal IroN-specific IgA response. In a
      mouse model of ascending urinary tract infection, subcutaneous immunization with
      denatured IroN conferred significant protection against renal (P = 0.0135 and
      0.0095 in two independent experiments), but not bladder, infection. These data,
      together with the previously demonstrated role of IroN in virulence, its
      expression in human biologic fluids, and its prevalence among extraintestinal
      pathogenic E. coli strains, support further studies on the role of IroN as a
      vaccine candidate.

PMID- 14638810
TI  - Deletion of Mycobacterium tuberculosis sigma factor E results in delayed time to
      death with bacterial persistence in the lungs of aerosol-infected mice.
AB  - The stress-induced extracytoplasmic sigma factor E (SigE) of Mycobacterium
      tuberculosis shows increased expression after heat shock, sodium dodecyl sulfate
      treatment, and oxidative stress, as well as after phagocytosis in macrophages. We
      report that deletion of sigE results in delayed lethality in mice without a
      significant reduction of bacterial numbers in lungs.

PMID- 14638811
TI  - CD8+-T-cell responses of Mycobacterium-infected mice to a newly identified major
      histocompatibility complex class I-restricted epitope shared by proteins of the
      ESAT-6 family.
AB  - Here we describe the identification of a new CD8(+)-T-cell epitope, the GYAGTLQSL
      nonamer, shared by the TB10.3 and TB10.4 proteins of the Mycobacterium
      tuberculosis ESAT-6 family. Cytotoxic T cells from mycobacterium-infected mice
      efficiently recognized this epitope. GYAGTLQSL-specific T-cell hybridomas, which
      were able to recognize Mycobacterium bovis BCG-infected macrophages, were
      generated and now allow investigation of mycobacterial-antigen processing through
      the major histocompatibility complex class I pathway.

PMID- 14638812
TI  - Haemophilus ducreyi requires an intact flp gene cluster for virulence in humans.
AB  - An intact Haemophilus ducreyi flp operon is essential for microcolony formation
      in vitro. tadA is the 9th of 15 genes in the operon and has homology to NTPases
      of type IV secretion systems. Fifteen human volunteers were experimentally
      infected with both H. ducreyi 35000HP and the tadA mutant, 35000HP.400. Papules
      developed at similar rates at sites inoculated with the mutant and parent, while
      pustules formed at 36.4% of parent sites and at 0% of mutant sites (P = 0.001).
      Compared to 35000HP, 35000HP.400 had only a modest but significant reduction in
      lesion scores in the temperature-dependent rabbit model of chancroid. These data
      suggest that proteins secreted by the flp locus are required for full expression
      of virulence by H. ducreyi in humans but have less of a role in virulence in an
      animal model of infection.

PMID- 14638814
TI  - Role of urease enzymes in stability of a 10-species oral biofilm consortium
      cultivated in a constant-depth film fermenter.
AB  - Using a 10-species oral biofilm consortium and defined mutants, we show that high
      level capacity to generate ammonia from a common salivary substrate is needed to
      maintain community diversity. This model appears to be suitable for the study of
      the effects of individual genetic determinants on the ecology of oral biofilms.

PMID- 14638813
TI  - Inducible nitric oxide synthase regulates production of isoprostanes in vivo
      during chlamydial genital infection in mice.
AB  - Urinary nitrite and F(2)-isoprostanes, an index of oxidant stress, were elevated
      during chlamydial genital infection of mice. Enhancement of urinary nitrite and
      F(2)-isoprostanes was observed in phagocyte oxidase-deficient mice. Inhibition of
      inducible nitric oxide synthase reduced isoprostane excretion. We conclude that
      nitrogen radicals induce F(2)-isoprostane production and excretion during murine
      chlamydial genital infection.

PMID- 14638815
TI  - The activation of bovine plasminogen by PauA is not required for virulence of
      Streptococcus uberis.
AB  - A mutant of Streptococcus uberis carrying a single copy of ISS1 within pauA was
      unable to activate bovine plasminogen. Contrary to a hypothesis postulated
      previously, this mutation did not alter the ability of the bacterium to grow in
      milk or to infect the lactating bovine mammary gland.

PMID- 14638816
TI  - Identification of B- and T-cell epitopes within the fibronectin-binding domain of
      the SfbI protein of Streptococcus pyogenes.
AB  - The fibronectin-binding repeats of the SfbI protein of Streptococcus pyogenes
      constitute the minimal domain able to confer protection against lethal infection.
      We investigated the presence of B- and T-cell epitopes within this region in
      congenic mice. One linear B-cell epitope was recognized by BALB/b and BALB/k
      mice, whereas two epitopes were found in BALB/c animals. A unique T-cell epitope
      was recognized by all three mouse strains. All identified epitopes clustered in a
      30-amino-acid fragment. These results suggest that this polypeptide may be
      suitable for incorporation into a polyepitope-based vaccine formulation against
      S. pyogenes.

PMID- 14638817
TI  - Genetic analysis of the capsule locus of Haemophilus influenzae serotype f.
AB  - A 19-kb DNA region containing genes involved in the biosynthesis of the capsule
      of Haemophilus influenzae serotype f (Hif) has been cloned and characterized. The
      Hif cap locus organization is typical of group II capsule biosynthetic loci found
      in other H. influenzae serotype b bacteria and other gram-negative bacteria.
      However, the Hif cap locus was not associated with an IS1016 element. Three new
      open reading frames, Fcs1, Fcs2, and Fcs3, were identified in the Hif capsule
      specific region II. The chromosomal location of the Hif cap locus and the
      organization of the flanking sequences differed significantly from previously
      described division I H. influenzae serotypes.

PMID- 14638818
TI  - Functional BvgAS virulence control system in Bordetella bronchiseptica is
      necessary for induction of Ca2+ transients in ciliated tracheal epithelial cells.
AB  - To study initial Bordetella bronchiseptica-tracheal epithelial cell interactions,
      we coincubated B. bronchiseptica with rabbit tracheal explant cultures and
      assayed bacterial adherence and host cell Ca(2+) signaling. Wild-type B.
      bronchiseptica (RB50) preferentially adhered to cilia and induced ciliated host
      cell Ca(2+) transients within 2 min of coincubation, whereas coincubation with an
      avirulent strain (RB57) resulted in limited binding and Ca(2+) signaling. The
      described cell system allows for assessment of initial B. bronchiseptica-host
      cell interactions that can contribute to pathogenicity or to host cell defense.

PMID- 14638819
TI  - Immunogenicity of Borrelia burgdorferi arthritis-related protein.
AB  - Immunization against arthritis-related protein (Arp) elicits antibody in mice
      that resolves arthritis but is not protective against challenge with Borrelia
      burgdorferi. In mice immunized against Arp, an unrelated 37-kDa protein (P37-42),
      outer surface protein A (OspA), or glutathione S-transferase (GT) and then
      challenged by syringe or tick, only OspA conferred protection. Passive transfer
      of Arp antiserum into infected SCID mice induced arthritis resolution, but
      antisera to P37-42, OspA, GT, or six overlapping Arp peptide fragments did not.
      Results suggest that the arthritis-resolving immunogenicity is specific to Arp,
      but the relevant epitopes may be conformational.

PMID- 14638820
TI  - High levels of susceptibility and T helper 2 response in MyD88-deficient mice
      infected with Leishmania major are interleukin-4 dependent.
AB  - Myeloid differentiation protein 88 (MyD88) is a general adaptor for the signaling
      cascade through receptors of the Toll/IL-1R family. When infected with Leishmania
      major parasites, MyD88-deficient mice displayed a dramatically enhanced parasite
      burden in their tissues similar to that found in susceptible BALB/c mice. In
      contrast, MyD88 knockout mice did not develop ulcerating lesions despite a lack
      of interleukin-12 (IL-12) production and a predominant T helper 2 cell response.
      Blockade of IL-4 produced early (day 1) after infection restored a protective T
      helper 1 response in MyD88 knockout mice.

PMID- 14638821
TI  - Abortive potency of Chlamydophila abortus in pregnant mice is not directly
      correlated with placental and fetal colonization levels.
AB  - Abortion, placental and fetal colonization, and levels of gamma interferon were
      analyzed for four Chlamydophila abortus strains presenting antigenic variations
      in a mouse model. Expression of virulence of these strains varied and indicated
      that abortion was not directly related to the number of bacteria in the placenta,
      and thus, other factors may have an important role in activating the abortion
      process.

PMID- 14638822
TI  - Mycobacterium avium subsp. paratuberculosis infection causes suppression of
      RANTES, monocyte chemoattractant protein 1, and tumor necrosis factor alpha
      expression in peripheral blood of experimentally infected cattle.
AB  - Blood from cattle with subclinical Mycobacterium avium subsp. paratuberculosis
      infection was stimulated with M. avium subsp. paratuberculosis antigens, and
      expression of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF
      alpha), RANTES, monocyte chemoattractant protein 1 (MCP-1), and IL-8 was
      measured. Expression of TNF-alpha, RANTES, and MCP-1 was lower in infected than
      in uninfected cattle. The reduced response may weaken protective immunity and
      perpetuate infection.

PMID- 14638823
TI  - Enhanced phagocytosis of Candida species mediated by opsonization with a
      recombinant human antibody single-chain variable fragment.
AB  - Specific antibody opsonization significantly enhances the level of phagocytosis
      of Candida in the absence of complement. Furthermore, we have described a system
      using a recombinant human antibody single-chain variable fragment that allows a
      comparative study of phagocytosis of multiple Candida species opsonized via a
      common antigen.

PMID- 14638824
TI  - Lipopolysaccharide from the periodontal pathogen Porphyromonas gingivalis
      prevents apoptosis of HL60-derived neutrophils in vitro.
AB  - Lipopolysaccharide (LPS) from Porphyromonas gingivalis prevented apoptosis of
      HL60-derived neutrophils, which could not be restored upon the addition of
      interleukin-10. Signaling of P. gingivalis LPS through Toll-like receptor 2
      (TLR2), not TLR4, may account for the inhibiting effect of P. gingivalis LPS on
      apoptosis and provide a mechanism for the development of destructive periodontal
      inflammation.

PMID- 14638826
TI  - Happy Anniversary JEB!

PMID- 14638825
TI  - Are cultures needed to enroll tuberculosis patients?

PMID- 14638828
TI  - Are hsps suitable for indicating stressed states in fish?
AB  - In response to most stressors, fish will elicit a generalized physiological
      stress response, which involves the activation of the hypothalamic-pituitary
      interrenal axis (HPI). As in other vertebrates, this generalized stress response
      comprises physiological responses that are common to a wide range of
      environmental, physical and biological stressors. Recently, several families of
      heat shock proteins (hsps) have been proposed as indicators of a generalized
      stress response at the cellular level. Recent findings that hsp levels, in
      various fish tissues, respond to a wide range of stressors have supported the use
      of these proteins as indicators of stressed states in fish. However, the cellular
      stress response can vary, for example, according to tissue, hsp family and type
      of stressor. This brief overview of these responses in fish asks the question of
      whether changes in levels and families of hsps can be used as a suitable
      indicator of stressed states in fish. By casting this question in the context of
      the well-established generalized physiological stress response in fish, we argue
      that the use of hsps as indicators of stressed states in fish in general is
      premature.

PMID- 14638829
TI  - Mechanism of tongue protraction in microhylid frogs.
AB  - High-speed videography and muscle denervation experiments were used to elucidate
      the mechanism of tongue protraction in the microhylid frog Phrynomantis
      bifasciatus. Unlike most frogs, Phrynomantis has the ability to protract the
      tongue through a lateral arc of over 200 degrees in the frontal plane. Thus, the
      tongue can be aimed side to side, independently of head and jaw movements.
      Denervation experiments demonstrate that the m. genioglossus complex controls
      lateral tongue aiming with a hydrostatic mechanism. After unilateral denervation
      of the m. genioglossus complex, the tongue can only be protracted towards the
      denervated (inactive) side and the range through which the tongue can be aimed is
      reduced by 75%. Histological sections of the tongue reveal a compartment of
      perpendicularly arranged muscle fibers, the m. genioglossus dorsoventralis. This
      compartment, in conjunction with the surrounding connective tissue, generates
      hydrostatic pressure that powers tongue movements in Phrynomantis. A survey of
      aiming abilities in 17 additional species of microhylid frogs, representing a
      total of 12 genera and six subfamilies, indicates that hydrostatic tongues are
      found throughout this family. Among frogs, this mechanism of tongue protraction
      was previously known only in Hemisus and may represent a synapomorphy of Hemisus
      and Microhylidae.

PMID- 14638830
TI  - Coward or braveheart: extreme habitat fidelity through hypoxia tolerance in a
      coral-dwelling goby.
AB  - Coral reef fishes are not known for their hypoxia tolerance. The coral-dwelling
      goby, Gobiodon histrio, rarely leaves the shelter of its host coral colony.
      However, our measurements indicate that this habitat could become hypoxic on calm
      nights ([O(2)] minima=2-30% of air saturation) due to respiration by the coral
      and associated organisms. Moreover, at very low tides, the whole coral colony can
      be completely air exposed. Using closed respirometry in water, we found that G.
      histrio maintains O(2) uptake down to 18% of air saturation, and that it can
      tolerate at least 2 h at even lower O(2) levels. Furthermore, during air
      exposure, which was tolerated for more than 3 h, it upheld a rate of O(2)
      consumption that was 60% of that in water. The hypoxia tolerance and air
      breathing abilities enables this fish to stay in the safety of its coral home
      even when exposed to severe hypoxia or air. To our knowledge, this is the first
      report of hypoxia tolerance in a teleost fish intimately associated with coral
      reefs.

PMID- 14638831
TI  - Body temperature and locomotor capacity in a heterothermic rodent.
AB  - We quantify the locomotor capacity of the round-tailed ground squirrel
      (Spermophilus tereticaudus), a mammal that can lower energetic costs by relaxing
      thermoregulatory limits without becoming inactive. We measured maximum sprint
      speed, maximum limb cycling frequency and maximum force production in animals at
      body temperatures ranging from 31 degrees C to 41 degrees C. We found no thermal
      dependence in any of these parameters of locomotion. Results (means +/- S.E.M.)
      across this range of body temperatures were: sprint speed = 4.73+/-0.04 m s(-1),
      limb cycling frequency = 19.4+/-0.1 Hz and maximum force production = 0.012+/
      0.0003 N g(-1). The neuro-muscular system of this species may thus be less
      thermally dependent at these temperatures than that of other mammals, allowing
      for the maintenance of whole-animal performance across a broader range of body
      temperatures. The absence of any significant loss of locomotor capabilities
      associated with either a decrease of 7-8 degrees C or a rise of 3-4 degrees C in
      body temperature from typical mammalian values raises significant questions
      regarding our understanding of the evolution and physiology of the mammalian mode
      of thermoregulation.

PMID- 14638832
TI  - Insect oviposition induces volatile emission in herbaceous plants that attracts
      egg parasitoids.
AB  - The egg parasitoid Trissolcus basalis (Wollaston) (Hymenoptera: Scelionidae)
      responded to synomones emitted by leguminous plants induced by feeding and
      oviposition activity of the bug Nezara viridula (L.) (Heteroptera: Pentatomidae).
      This was shown by laboratory bioassays using a Y-tube olfactometer. Broad bean
      leaves (Vicia faba L.) damaged by feeding activity of N. viridula and on which
      host egg mass had been laid produced synomones that attracted T. basalis. By
      contrast, undamaged leaves or feeding-damaged leaves without eggs did not attract
      wasp females. French bean plants (Phaseolus vulgaris L.) also emitted attractive
      synomones when they were damaged by host feeding and carrying egg masses. Thus,
      release of feeding- and oviposition-induced synomones does not seem to be plant
      specific. Synomone production was shown to be a systemically induced plant
      physiological response to feeding damage and oviposition. Also, parts of the
      plant that were left undamaged and did not carry host eggs emitted attractive
      synomones when other parts of the plant were damaged by feeding and carrying
      eggs. Furthermore, wasps were not attracted by N. viridula egg masses offered
      alone or combined with damaged broad bean leaves. Thus, the attractiveness of
      feeding-damaged leaves carrying eggs is due to induction by feeding and
      oviposition rather than due to a combined effect of attractive volatiles released
      from eggs and damaged leaves. The production of synomones was influenced by the
      age of the host egg mass, because feeding-damaged leaves bearing egg masses
      attracted the parasitoid until the eggs were approximately 72-96 h old but not
      once the larvae had hatched from the eggs (approximately 120 h old). These
      results show that annual plants are able to produce synomones as a consequence of
      feeding and egg mass oviposition by a sucking insect.

PMID- 14638833
TI  - Characterization of a novel set of resident intrathyroidal bone marrow-derived
      hematopoietic cells: potential for immune-endocrine interactions in thyroid
      homeostasis.
AB  - Immunofluorescent staining of thyroid tissues was done using monoclonal
      antibodies to dendritic cell (DC), lymphocyte, macrophage and granulocyte
      markers. Despite the presence of occasional CD11c+ cells, CD11b+ cells,
      morphologically characteristic of DCs, were abundant in thyroid of normal mice,
      at a density of approximately 2.0 cells per thyroid follicle, and were >tenfold
      more frequent than CD11c+ cells. Thyroid tissues were non-reactive with
      antibodies to F4/80, CD8alpha, CD40, CD80, Gr-1, CD3, or CD19, indicating that
      the CD11b+ cells were not macrophages, activated DCs, granulocytes, plasmacytoid
      DCs, T cells or B cells. Following systemic immune activation, DCs in secondary
      lymphoid tissues but not in the thyroid, upregulated CD80 expression. Using
      radiation chimeras made from bone marrow from enhanced green fluorescent protein
      (EGFP) transgenic mice, EGFP+ DC-like cells were present in the thyroid from 1-20
      weeks after bone marrow transfer, but were rare in the kidney and liver, although
      EGFP+ cells were present in secondary lymphoid tissues. Additionally, DCs
      generated from EGFP+ bone marrow cells localized in the thyroid of EGFP- mice
      following adoptive transfer. Double staining of thyroid tissue sections with
      antibodies to the thyroid stimulating hormone (TSH)-beta molecule and to CD11b
      revealed co-expression of TSHbeta and CD11b among intrathyroidal DCs. Moreover,
      RT-PCR analyses indicated expression of the TSHbeta gene in thyroid tissues.
      These findings define a novel bone marrow-derived hematopoietic cell population
      that resides in the thyroid of normal mice, which may have a unique role in the
      microregulation of thyroid physiology and homeostasis.

PMID- 14638834
TI  - Biomechanics of ant adhesive pads: frictional forces are rate- and temperature
      dependent.
AB  - Tarsal adhesive pads enable insects to hold on to smooth plant surfaces. Using a
      centrifuge technique, we tested whether a "wet adhesion" model of a thin film of
      liquid secreted between the pad and the surface can explain adhesive and
      frictional forces in Asian Weaver ants (Oecophylla smaragdina). When forces are
      acting parallel to the surface, pads in contact with the surface can slide
      smoothly. Force per unit pad contact area was strongly dependent on sliding
      velocity and temperature. Seemingly consistent with the effect of a thin liquid
      film in the contact zone, (1) frictional force linearly increased with sliding
      velocity, (2) the increment was greater at lower temperatures and (3) no
      temperature dependence was detected for low-rate perpendicular detachment forces.
      However, we observed a strong, temperature-independent static friction that was
      inconsistent with a fully lubricated contact. Static friction was too large to be
      explained by the contribution of other (sclerotized) body parts. Moreover, the
      rate-specific increase of shear stress strongly exceeded predictions derived from
      estimates of the adhesive liquid film's thickness and viscosity. Both lines of
      evidence indicate that the adhesive secretion alone is insufficient to explain
      the observed forces and that direct interaction of the soft pad cuticle with the
      surface ("rubber friction") is involved.

PMID- 14638835
TI  - Physiological modulation of iron metabolism in rainbow trout (Oncorhynchus
      mykiss) fed low and high iron diets.
AB  - Iron (Fe) is an essential element, but Fe metabolism is poorly described in fish
      and the role of ferrireductase and transferrin in iron regulation by teleosts is
      unknown. The aim of the present study was to provide an overview of the strategy
      for Fe handling in rainbow trout, Oncorhynchus mykiss. Fish were fed Fe
      deficient, normal and high-Fe diets (33, 175, 1975 mg Fe kg(-1) food,
      respectively) for 8 weeks. Diets were chosen so that no changes in growth, food
      conversion ratio, haematology, or significant oxidative stress (TBARS) were
      observed. Elevation of dietary Fe caused Fe accumulation particularly in the
      stomach, intestine, liver and blood. The increase in total serum Fe from 10 to 49
      micro mol l(-1) over 8 weeks was associated with elevated total Fe binding
      capacity and decreased unsaturated Fe binding capacity, so that in fish fed a
      high-Fe diet transferrin saturation increased from 15% at the start of the
      experiment to 37%. Fish on the high-Fe diet increased Fe accumulation in the
      liver, which was correlated with elevation of hepatic ferrireductase activity and
      serum transferrin saturation. Conversely, fish on the low-Fe diet did not show
      tissue Fe depletion compared with normal diet controls and did not change Fe
      binding to serum transferrin. Instead, these fish doubled intestinal
      ferrireductase activity which may have contributed to the maintenance of tissue
      Fe status. The absence of clear treatment-dependent changes in branchial Fe
      accumulation and ferrireductase activity indicated that the gills do not have a
      major role in Fe metabolism. Some transient changes in Cu, Zn and Mn status of
      tissues occurred.

PMID- 14638836
TI  - Learning, odour preference and flower foraging in moths.
AB  - Floral volatiles play a major role in plant-insect communication. We examined the
      influence of two volatiles, phenylacetaldehyde and alpha-pinene, on the innate
      and learnt foraging behaviour of the moth Helicoverpa armigera. In dual-choice
      wind tunnel tests, adult moths flew upwind towards both volatiles, with a
      preference for phenylacetaldehyde. When exposure to either of these volatiles was
      paired with a feeding stimulus (sucrose), all moths preferred the learnt odour in
      the preference test. This change in preference was not seen when moths were
      exposed to the odour without a feeding stimulus. The learnt preference for the
      odour was reduced when moths were left unfed for 24 h before the preference test.
      We tested whether moths could discriminate between flowers that differed in a
      single volatile component. Moths were trained to feed on flowers that were odour
      enhanced using either phenylacetaldehyde or alpha-pinene. Choice tests were then
      carried out in an outdoor flight cage, using flowers enhanced with either
      volatile. Moths showed a significant preference for the flower type on which they
      were trained. Moths that were conditioned on flowers that were not odour-enhanced
      showed no preference for either of the odour-enhanced flower types. The results
      imply that moths may be discriminating among odour profiles of individual flowers
      from the same species. We discuss this behaviour within the context of nectar
      foraging in moths and odour signalling by flowering plants.

PMID- 14638837
TI  - Effects of temperature acclimation on lactate dehydrogenase of cod (Gadus
      morhua): genetic, kinetic and thermodynamic aspects.
AB  - The aim of this study was to determine the effects of seasonal temperature
      variation on the functional properties of lactate dehydrogenase (LDH) from white
      muscle and liver of Norwegian coastal cod (Gadus morhua) and the possible
      relevance of LDH allelic variability for thermal acclimation. Two groups of
      fishes were acclimated to 4 degrees C or 12 degrees C for one year. Polymorphism
      was observed in only one (Ldh-B) of the three Ldh loci expressed in cod liver
      and/or muscle. Isozyme expression remained unchanged regardless of acclimation
      temperature (T(A)). The products of locus Ldh-B comprise only 14-19% (depending
      on the tissue) of total LDH activities and, consequently, differences between
      phenotypes are negligible in terms of their effect on LDH total performance. No
      kinetic (, V(max)) or thermodynamic (E(a), DeltaG) differences were found among
      Ldh-B phenotypes. Clear kinetic differences were observed between LDH isoforms in
      the two tissues. However, the Arrhenius activation energy (E(a)) for pyruvate
      reduction was the same for both tissues (E(a)=47 kJ mol(-1)) at T(A)=12 degrees
      C. Factors T(A), tissue and phenotype did not reveal a significant effect on the
      Gibbs free energy change (DeltaG) of the reaction (55.5 kJ mol(-1)). However, at
      T(A)=4 degrees C, the E(a) was increased (E(a)=53-56 kJ mol(-1)) and the
      temperature dependence of the constant of substrate inhibition for pyruvate ()
      decreased in both muscle and liver. In conclusion, the strategies of LDH
      adjustment to seasonal temperature variations in cod involve changes in LDH
      concentration (quantitative), adjustment of thermodynamic (E(a)) and kinetic ()
      properties of the LDH (modulative) but not the expression of alternative isoforms
      (qualitative). We assume that the observed increase in E(a) and the decrease of
      temperature dependence of at low T(A) is the result of structural changes of the
      LDH molecule (temperature-driven protein folding). We propose a new mechanism of
      metabolic compensation of seasonal temperature variations - cold acclimation
      results in changes in the kinetic and thermodynamic properties of LDH in a way
      that favours aerobic metabolism through reduction of the competition of LDH for
      pyruvate in normoxic conditions.

PMID- 14638838
TI  - Spatial organization of visuomotor reflexes in Drosophila.
AB  - In most animals, the visual system plays a central role in locomotor guidance.
      Here, we examined the functional organization of visuomotor reflexes in the fruit
      fly, Drosophila, using an electronic flight simulator. Flies exhibit powerful
      avoidance responses to visual expansion centered laterally. The amplitude of
      these expansion responses is three times larger than those generated by image
      rotation. Avoidance of a laterally positioned focus of expansion emerges from an
      inversion of the optomotor response when motion is restricted to the rear visual
      hemisphere. Furthermore, motion restricted to rear quarter-fields elicits turning
      responses that are independent of the direction of image motion about the
      animal's yaw axis. The spatial heterogeneity of visuomotor responses explains a
      seemingly peculiar behavior in which flies robustly fixate the contracting pole
      of a translating flow field.

PMID- 14638839
TI  - Motor output reflects the linear superposition of visual and olfactory inputs in
      Drosophila.
AB  - Animals actively seeking food and oviposition sites must integrate feedback from
      multiple sensory modalities. Here, we examine visual and olfactory sensorimotor
      interactions in Drosophila. In a tethered-flight simulator, flies modulate
      wingbeat frequency and amplitude in response to visual and olfactory stimuli.
      Responses to both cues presented simultaneously are nearly identical to the sum
      of responses to stimuli presented in isolation for the onset and duration of odor
      delivery, suggesting independent sensorimotor pathways. Visual feedback does,
      however, alter the time course of the odor-off response. Based on the physiology
      of the flight motor system and recent free-flight analyses, we present a
      hypothetical model to account for the summation or superposition of sensorimotor
      responses during flight.

PMID- 14638840
TI  - Summation of visual and mechanosensory feedback in Drosophila flight control.
AB  - The fruit fly Drosophila melanogaster relies on feedback from multiple sensory
      modalities to control flight maneuvers. Two sensory organs, the compound eyes and
      mechanosensory hindwings called halteres, are capable of encoding angular
      velocity of the body during flight. Although motor reflexes driven by the two
      modalities have been studied individually, little is known about how the two
      sensory feedback channels are integrated during flight. Using a specialized
      flight simulator we presented tethered flies with simultaneous visual and
      mechanosensory oscillations while measuring compensatory changes in stroke
      kinematics. By varying the relative amplitude, phase and axis of rotation of the
      visual and mechanical stimuli, we were able to determine the contribution of each
      sensory modality to the compensatory motor reflex. Our results show that over a
      wide range of experimental conditions sensory inputs from halteres and the visual
      system are combined in a weighted sum. Furthermore, the weighting structure
      places greater influence on feedback from the halteres than from the visual
      system.

PMID- 14638841
TI  - The low-affinity glucocorticoid receptor regulates feeding and lipid breakdown in
      the migratory Gambel's white-crowned sparrow Zonotrichia leucophrys gambelii.
AB  - Plasma corticosterone increases during spring migration in a variety of bird
      species, including the Gambel's white-crowned sparrow Zonotrichia leucophrys
      gambelii. Corticosterone is elevated specifically in association with migratory
      flight, suggesting that corticosterone may promote processes such as energy
      mobilization and/or migratory activity. General effects of glucocorticoids
      support such a prediction. Because glucocorticoids exert permissive effects on
      food intake, corticosterone may also participate in the regulation of migratory
      hyperphagia. To examine the role of corticosterone during migration, we induced
      Gambel's white-crowned sparrows to enter the migratory condition and compared
      food intake and locomotor activity between controls and birds injected with RU486
      -an antagonist to the low-affinity glucocorticoid receptor (GR). In addition, we
      investigated effects of RU486 in birds that were subjected to a short-term fast.
      Results indicate that RU486 did not affect locomotor activity. However,
      consistent with its effects in mammals, RU486 suppressed food intake. Thus,
      hyperphagia and migratory restlessness, the two behaviors that characterize
      migration, may be regulated by different mechanisms. Lastly, RU486 antagonized
      fasting-induced lipid mobilization, as evidenced by decreased plasma free fatty
      acids. Thus, data on spring migrants suggest that endogenous corticosterone
      levels act through the GR to support hyperphagia and that the GR promotes
      availability of lipid fuel substrates in association with periods of energetic
      demand, e.g. during migratory flight.

PMID- 14638842
TI  - Development of ultrasound detection in American shad (Alosa sapidissima).
AB  - It has recently been shown that a few fish species, including American shad
      (Alosa sapidissima; Clupeiformes), are able to detect sound up to 180 kHz, an
      ability not found in most other fishes. Initially, it was proposed that
      ultrasound detection in shad involves the auditory bullae, swim bladder
      extensions found in all members of the Clupeiformes. However, while all
      clupeiformes have bullae, not all can detect ultrasound. Thus, the bullae alone
      are not sufficient to explain ultrasound detection. In this study, we used a
      developmental approach to determine when ultrasound detection begins and how the
      ability to detect ultrasound changes with ontogeny in American shad. We then
      compared changes in auditory function with morphological development to identify
      structures that are potentially responsible for ultrasound detection. We found
      that the auditory bullae and all three auditory end organs are present well
      before fish show ultrasound detection behaviourally and we suggest that an
      additional specialization in the utricle (one of the auditory end organs) forms
      coincident with the onset of ultrasound detection. We further show that this
      utricular specialization is found in two clupeiform species that can detect
      ultrasound but not in two clupeiform species not capable of ultrasound detection.
      Thus, it appears that ultrasound-detecting clupeiformes have undergone structural
      modification of the utricle that allows detection of ultrasonic stimulation.

PMID- 14638843
TI  - Photoperiodic effects on body mass, energy balance and hypothalamic gene
      expression in the bank vole.
AB  - We examined the effect of increasing photoperiod, at a constant low temperature,
      on the body mass and energy budget of the bank vole Clethrionomys glareolus.
      Simultaneously, we determined the hypothalamic gene expression of neuropeptides
      and receptors known to be involved in short-term energy balance. Despite an
      increase in body mass (approximately 10% of initial mass), we found no
      significant changes in any energetic parameters (food intake, energy assimilation
      rate, resting metabolic rate and total daily energy expenditure by doubly
      labelled water). Apparent energy assimilation efficiency was higher in voles
      exposed to long-days (LD) compared to short-days (SD). Surprisingly, gene
      expression of corticotrophin releasing factor (CRF; in the paraventricular
      nucleus), and the melanocortin-3 receptor (in the arcuate nucleus), both known to
      be involved in appetite suppression and elevation of energy expenditure in short
      term energy balance, were higher in voles kept in LD compared to SD. CRF
      expression was also elevated in females compared to males. These paradoxical data
      suggest an alternative mechanism for the control of seasonal body mass changes
      compared to short-term body mass changes, and between male and female voles.
      Furthermore, they highlight the need for studies to perform simultaneous
      measurements at both the molecular and whole animal levels.

PMID- 14638844
TI  - Visual learning in individually assayed Drosophila larvae.
AB  - An understanding of associative learning is facilitated if it can be analyzed in
      a simple animal like the fruit fly Drosophila. Here, we introduce the first
      visual associative learning paradigm for larval Drosophila; this is remarkable as
      larvae have an order of magnitude fewer neurons than adult flies. Larvae were
      subjected to either of two reciprocal training regimes: Light+/Dark- or Light
      /Dark+. Subsequently, all larvae were individually tested for their preference
      between Light versus Dark. The difference between training regimes was therefore
      exclusively which visual situation was associated with which reinforcer;
      differences observed during the test thus reflected exclusively associative
      learning. For positive reinforcement (+) we used fructose (FRU), and for negative
      reinforcement (-) either quinine or sodium chloride (QUI, NaCl). Under these
      conditions, associative learning could be reproducibly observed in both wild-type
      strains tested. We then compared the effectiveness of training using differential
      conditioning, with both positive and negative reinforcement, to that using only
      positive or only negative reinforcement. We found that FRU only, but neither QUI
      nor NaCl, was in itself effective as a reinforcer. This is the first
      demonstration of appetitive learning in larval Drosophila. It is now possible to
      investigate the behavioral and neuronal organization of appetitive visual
      learning in this simple and genetically easy-to-manipulate experimental system.

PMID- 14638845
TI  - Lymphotoxin is required for maintaining physiological levels of serum IgE that
      minimizes Th1-mediated airway inflammation.
AB  - Although elevated levels of IgE in asthmatic patients are strongly associated
      with lung infiltration by activated T helper (Th) 2 cells, the physiological role
      of immunoglobulin E (IgE) in the airway remains largely undefined. Lymphotoxin
      deficient alpha (LTalpha-/-) mice exhibit increased airway inflammation,
      paradoxically accompanied by diminished levels of IgE and reduced airway
      hyperresponsiveness in response to both environmental and induced antigen
      challenge. The severe lung inflammation in LTalpha-/- mice is Th1 in nature and
      can be alleviated by IgE reconstitution. Conversely, depletion of IgE in wild
      type mice recapitulates the lung pathologies of LTalpha-/- mice. Therefore, this
      work has revealed that lymphotoxin is essential for IgE production, and a
      physiological role of IgE in the airway may consist of maintaining the balance of
      Th1 and Th2 responses to prevent aberrant inflammation.

PMID- 14638846
TI  - Vigorous premalignancy-specific effector T cell response in the bone marrow of
      patients with monoclonal gammopathy.
AB  - Most approaches targeting the immune system against tumors have focused on
      patients with established tumors. However, whether the immune system can
      recognize preneoplastic stages of human cancer is not known. Here we show that
      patients with preneoplastic gammopathy mount a vigorous T cell response to
      autologous premalignant cells. This preneoplasia-specific CD4+ and CD8+ T cell
      response is detected in freshly isolated T cells from the BM. T cells from
      myeloma marrow lack this tumor-specific rapid effector function. These data
      provide direct evidence for tumor specific immune recognition in human
      preneoplasia and suggest a possible role for the immune system in influencing the
      early growth of transformed cells, long before the development of clinical
      cancer.

PMID- 14638847
TI  - Identification of a pre-BCR lacking surrogate light chain.
AB  - SLP-65-/- pre-B cells show a high proliferation rate in vitro. We have shown
      previously that lambda5 expression and consequently a conventional pre-B cell
      receptor (pre-BCR) are essential for this proliferation. Here, we show that pre-B
      cells express a novel receptor complex that contains a micro heavy chain
      (microHC) but lacks any surrogate (SL) or conventional light chain (LC). This SL
      deficient pre-BCR (SL-pre-BCR) requires Ig-alpha for expression on the cell
      surface. Anti-micro treatment of pre-B cells expressing the SL-pre-BCR induces
      tyrosine phosphorylation of substrate proteins and a strong calcium (Ca2+)
      release. Further, the expression of the SL-pre-BCR is associated with a high
      differentiation rate toward kappaLC-positive cells. Given that B cell development
      is only partially blocked and allelic exclusion is unaffected in SL-deficient
      mice, we propose that the SL-pre-BCR is involved in these processes and therefore
      shares important functions with the conventional pre-BCR.

PMID- 14638848
TI  - IL-4-Stat6 signaling induces tristetraprolin expression and inhibits TNF-alpha
      production in mast cells.
AB  - Increasing evidence has revealed that mast cell-derived tumor necrosis factor
      alpha (TNF-alpha) plays a critical role in a number of inflammatory responses by
      recruiting inflammatory leukocytes. In this paper, we investigated the regulatory
      role of interleukin 4 (IL-4) in TNF-alpha production in mast cells. IL-4
      inhibited immunoglobulin E-induced TNF-alpha production and neutrophil
      recruitment in the peritoneal cavity in wild-type mice but not in signal
      transducers and activators of transcription 6 (Stat6)-deficient mice. IL-4 also
      inhibited TNF-alpha production in cultured mast cells by a Stat6-dependent
      mechanism. IL-4-Stat6 signaling induced TNF-alpha mRNA destabilization in an AU
      rich element (ARE)-dependent manner, but did not affect TNF-alpha promoter
      activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an
      RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by
      a Stat6-dependent mechanism, and the depletion of TTP expression by RNA
      interference prevented IL-4-induced down-regulation of TNF-alpha production in
      mast cells. These results suggest that IL-4-Stat6 signaling induces TTP
      expression and, thus, destabilizes TNF-alpha mRNA in an ARE-dependent manner.

PMID- 14638849
TI  - Premalignant lesions as targets for cancer vaccines.

PMID- 14638850
TI  - Phase II trial of gefitinib in recurrent glioblastoma.
AB  - PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa;
      AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine
      kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS:
      This was an open-label, single-center phase II trial. Fifty-seven patients with
      first recurrence of a glioblastoma who were previously treated with surgical
      resection, radiation, and usually chemotherapy underwent an open biopsy or
      resection at evaluation for confirmation of tumor recurrence. Each patient
      initially received 500 mg of gefitinib orally once daily; dose escalation to 750
      mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or
      dexamethasone, was allowed within each patient. RESULTS: Although no objective
      tumor responses were seen among the 53 assessable patients, only 21% of patients
      (11 of 53 patients) had measurable disease at treatment initiation. Seventeen
      percent of patients (nine of 53 patients) underwent at least six 4-week cycles,
      and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The
      median EFS time was 8.1 weeks, and the median overall survival (OS) time from
      treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1
      or 2) and consisted mainly of skin reactions and diarrhea. Drug-related
      toxicities were more frequent at higher doses. Withdrawal caused by drug-related
      adverse events occurred in 6% of patients (three of 53 patients). Although the
      presence of diarrhea positively predicted favorable OS from treatment initiation,
      epidermal growth factor receptor expression did not correlate with either EFS or
      OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with
      recurrent glioblastoma. Further study of this agent at higher doses is warranted.

PMID- 14638852
TI  - Breathing down the neck of Unc104.
AB  - The Unc104/Kif1A class of kinesins transports synaptic vesicle precursors along
      microtubules with high speed and processivity that has been proposed to depend on
      reversible dimerization between two poorly motile monomers. In this issue, Al
      Bassam et al. (2003) discover a structural basis for regulation of motility by
      reversible dimerization.

PMID- 14638851
TI  - Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy
      gene.
AB  - Malignant cells often display defects in autophagy, an evolutionarily conserved
      pathway for degrading long-lived proteins and cytoplasmic organelles. However, as
      yet, there is no genetic evidence for a role of autophagy genes in tumor
      suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of
      cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used
      a targeted mutant mouse model to test the hypothesis that monoallelic deletion of
      beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of
      beclin 1 increases the frequency of spontaneous malignancies and accelerates the
      development of hepatitis B virus-induced premalignant lesions. Molecular analyses
      of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele
      is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption
      results in increased cellular proliferation and reduced autophagy in vivo. These
      findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene
      and provide genetic evidence that autophagy is a novel mechanism of cell-growth
      control and tumor suppression. Thus, mutation of beclin 1 or other autophagy
      genes may contribute to the pathogenesis of human cancers.

PMID- 14638853
TI  - Cdk5 and the mystery of synaptic vesicle endocytosis.
AB  - Regulation of endocytosis by protein phosphorylation and dephosphorylation is
      critical to synaptic vesicle recycling. Two groups have now identified the
      neuronal kinase Cdk5 (cyclin-dependent kinase 5) as an important regulator of
      this process. Robinson and coworkers recently demonstrated that Cdk5 is necessary
      for synaptic vesicle endocytosis (SVE) (Tan et al., 2003), whereas a new report
      in this issue claims that Cdk5 negatively regulates SVE (Tomizawa et al., 2003).
      Careful examination of the data reveals a model that helps resolve the apparently
      contradictory nature of these reports.

PMID- 14638854
TI  - The Drosophila nucleoporin DNup88 localizes DNup214 and CRM1 on the nuclear
      envelope and attenuates NES-mediated nuclear export.
AB  - Many cellular responses rely on the control of nucleocytoplasmic transport of
      transcriptional regulators. The Drosophila nucleoporin Nup88 is selectively
      required for nuclear accumulation of Rel proteins and full activation of the
      innate immune response. Here, we investigate the mechanisms underlying its role
      in nucleocytoplasmic transport. Nuclear import of an nuclear localization signal
      enhanced green fluorescent protein (NLS-EGFP) reporter is not affected in DNup88
      (members only; mbo) mutants, whereas the level of CRM1-dependent EGFP-nuclear
      export signal (EGFP-NES) export is increased. We show that the nuclear
      accumulation of the Drosophila Rel protein Dorsal requires CRM1. DNup88 binds to
      DNup214 and DCRM1 in vitro, and both proteins become mislocalized from the
      nuclear rim into the nucleus of mbo mutants. Overexpression of DNup88 is
      sufficient to relocalize DNup214 and CRM1 on the nuclear envelope and revert the
      mutant phenotypes. We propose that a major function of DNup88 is to anchor
      DNup214 and CRM1 on the nuclear envelope and thereby attenuate NES-mediated
      nuclear export.

PMID- 14638855
TI  - A J-protein is an essential subunit of the presequence translocase-associated
      protein import motor of mitochondria.
AB  - Transport of preproteins into the mitochondrial matrix is mediated by the
      presequence translocase-associated motor (PAM). Three essential subunits of the
      motor are known: mitochondrial Hsp70 (mtHsp70); the peripheral membrane protein
      Tim44; and the nucleotide exchange factor Mge1. We have identified the fourth
      essential subunit of the PAM, an essential inner membrane protein of 18 kD with a
      J-domain that stimulates the ATPase activity of mtHsp70. The novel J-protein
      (encoded by PAM18/YLR008c/TIM14) is required for the interaction of mtHsp70 with
      Tim44 and protein translocation into the matrix. We conclude that the reaction
      cycle of the PAM of mitochondria involves an essential J-protein.

PMID- 14638856
TI  - Dynamics and calcium sensitivity of the Ca2+/myristoyl switch protein hippocalcin
      in living cells.
AB  - Hippocalcin is a neuronal calcium sensor protein that possesses a Ca2+/myristoyl
      switch allowing it to translocate to membranes. Translocation of hippocalcin in
      response to increased cytosolic [Ca2+] was examined in HeLa cells expressing
      hippocalcin-enhanced yellow fluorescent protein (EYFP) to determine the dynamics
      and Ca2+ affinity of the Ca2+/myristoyl switch in living cells. Ca2+-free
      hippocalcin was freely diffusible, as shown by photobleaching and use of a
      photoactivable GFP construct. The translocation was dependent on binding of Ca2+
      by EF-hands 2 and 3. Using photolysis of NP-EGTA, the maximal kinetics of
      translocation was determined (t1/2 = 0.9 s), and this was consistent with a
      diffusion driven process. Low intensity photolysis of NP-EGTA produced a slow
      [Ca2+] ramp and revealed that translocation of hippocalcin-EYFP initiated at
      around 180 nM and was half maximal at 290 nM. Histamine induced a reversible
      translocation of hippocalcin-EYFP. The data show that hippocalcin is a sensitive
      Ca2+ sensor capable of responding to increases in intracellular Ca2+
      concentration over the narrow dynamic range of 200-800 nM free Ca2+.

PMID- 14638857
TI  - Cross-talk between the Notch and TGF-beta signaling pathways mediated by
      interaction of the Notch intracellular domain with Smad3.
AB  - The Notch and transforming growth factor-beta (TGF-beta) signaling pathways play
      critical roles in the control of cell fate during metazoan development. However,
      mechanisms of cross-talk and signal integration between the two systems are
      unknown. Here, we demonstrate a functional synergism between Notch and TGF-beta
      signaling in the regulation of Hes-1, a direct target of the Notch pathway.
      Activation of TGF-beta signaling up-regulated Hes-1 expression in vitro and in
      vivo. This effect was abrogated in myogenic cells by a dominant-negative form of
      CSL, an essential DNA-binding component of the Notch pathway. TGF-beta regulated
      transcription from the Hes-1 promoter in a Notch-dependent manner, and the
      intracellular domain of Notch1 (NICD) cooperated synergistically with Smad3, an
      intracellular transducer of TGF-beta signals, to induce the activation of
      synthetic promoters containing multimerized CSL- or Smad3-binding sites. NICD and
      Smad3 were shown to interact directly, both in vitro and in cells, in a ligand
      dependent manner, and Smad3 could be recruited to CSL-binding sites on DNA in the
      presence of CSL and NICD. These findings indicate that Notch and TGF-beta signals
      are integrated by direct protein-protein interactions between the signal
      transducing intracellular elements from both pathways.

PMID- 14638858
TI  - Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer
      motor transition.
AB  - Caenhorhabditis elegans Unc104 kinesin transports synaptic vesicles at rapid
      velocities. Unc104 is primarily monomeric in solution, but recent motility
      studies suggest that it may dimerize when concentrated on membranes. Using cryo
      electron microscopy, we observe two conformations of microtubule-bound Unc104: a
      monomeric state in which the two neck helices form an intramolecular, parallel
      coiled coil; and a dimeric state in which the neck helices form an intermolecular
      coiled coil. The intramolecular folded conformation is abolished by deletion of a
      flexible hinge separating the neck helices, indicating that it acts as a spacer
      to accommodate the parallel coiled-coil configuration. The neck hinge deletion
      mutation does not alter motor velocity in vitro but produces a severe
      uncoordinated phenotype in transgenic C. elegans, suggesting that the folded
      conformation plays an important role in motor regulation. We suggest that the
      Unc104 neck regulates motility by switching from a self-folded, repressed state
      to a dimerized conformation that can support fast processive movement.

PMID- 14638859
TI  - Mammalian GGAs act together to sort mannose 6-phosphate receptors.
AB  - The GGAs (Golgi-localized, gamma ear-containing, ADP ribosylation factor-binding
      proteins) are multidomain proteins implicated in protein trafficking between the
      Golgi and endosomes. We examined whether the three mammalian GGAs act
      independently or together to mediate their functions. Using cryo-immunogold
      electron microscopy, the three GGAs were shown to colocalize within coated buds
      and vesicles at the trans-Golgi network (TGN) of HeLa cells. In vitro binding
      experiments revealed multidomain interactions between the GGAs, and chemical
      cross-linking experiments demonstrated that GGAs 1 and 2 form a complex on Golgi
      membranes. RNA interference of each GGA resulted in decreased levels of the other
      GGAs and their redistribution from the TGN to cytosol. This was associated with
      impaired incorporation of the cation-independent mannose 6-phosphate receptor
      into clathrin-coated vesicles at the TGN, partial redistribution of the receptor
      to endosomes, and missorting of cathepsin D. The morphology of the TGN was also
      altered. These findings indicate that the three mammalian GGAs cooperate to sort
      cargo and are required for maintenance of TGN structure.

PMID- 14638860
TI  - Inhibition of a constitutive translation initiation factor 2alpha phosphatase,
      CReP, promotes survival of stressed cells.
AB  - Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) on
      serine 51 is effected by specific stress-activated protein kinases. eIF2alpha
      phosphorylation inhibits translation initiation promoting a cytoprotective gene
      expression program known as the integrated stress response (ISR). Stress-induced
      activation of GADD34 feeds back negatively on this pathway by promoting eIF2alpha
      dephosphorylation, however, GADD34 mutant cells retain significant eIF2alpha
      directed phosphatase activity. We used a somatic cell genetic approach to
      identify a gene encoding a novel regulatory subunit of a constitutively active
      holophosphatase complex that dephosphorylates eIF2alpha. RNAi of this gene, which
      we named constitutive repressor of eIF2alpha phosphorylation (CReP, or PPP1R15B),
      repressed the constitutive eIF2alpha-directed phosphatase activity and activated
      the ISR. CReP RNAi strongly protected mammalian cells against oxidative stress,
      peroxynitrite stress, and more modestly against accumulation of malfolded
      proteins in the endoplasmic reticulum. These findings suggest that therapeutic
      inhibition of eIF2alpha dephosphorylation by targeting the CReP-protein
      phosphatase-1 complex may be used to access the salubrious qualities of the ISR.

PMID- 14638861
TI  - The stromal cell-derived factor-1alpha/CXCR4 ligand-receptor axis is critical for
      progenitor survival and migration in the pancreas.
AB  - The SDF-1alpha/CXCR4 ligand/chemokine receptor pair is required for appropriate
      patterning during ontogeny and stimulates the growth and differentiation of
      critical cell types. Here, we demonstrate SDF-1alpha and CXCR4 expression in
      fetal pancreas. We have found that SDF-1alpha and its receptor CXCR4 are
      expressed in islets, also CXCR4 is expressed in and around the proliferating duct
      epithelium of the regenerating pancreas of the interferon (IFN) gamma-nonobese
      diabetic mouse. We show that SDF-1alpha stimulates the phosphorylation of Akt,
      mitogen-activated protein kinase, and Src in pancreatic duct cells. Furthermore,
      migration assays indicate a stimulatory effect of SDF-1alpha on ductal cell
      migration. Importantly, blocking the SDF-1alpha/CXCR4 axis in IFNgamma-nonobese
      diabetic mice resulted in diminished proliferation and increased apoptosis in the
      pancreatic ductal cells. Together, these data indicate that the SDF-1alpha-CXCR4
      ligand receptor axis is an obligatory component in the maintenance of duct cell
      survival, proliferation, and migration during pancreatic regeneration.

PMID- 14638862
TI  - Nucleolin expressed at the cell surface is a marker of endothelial cells in
      angiogenic blood vessels.
AB  - A tumor-homing peptide, F3, selectively binds to endothelial cells in tumor blood
      vessels and to tumor cells. Here, we show that the cell surface molecule
      recognized by F3 is nucleolin. Nucleolin specifically bound to an F3 peptide
      affinity matrix from extracts of cultured breast carcinoma cells. Antibodies and
      cell surface biotin labeling revealed nucleolin at the surface of actively
      growing cells, and these cells bound and internalized fluorescein-conjugated F3
      peptide, transporting it into the nucleus. In contrast, nucleolin was exclusively
      nuclear in serum-starved cells, and F3 did not bind to these cells. The binding
      and subsequent internalization of F3 were blocked by an antinucleolin antibody.
      Like the F3 peptide, intravenously injected antinucleolin antibodies selectively
      accumulated in tumor vessels and in angiogenic vessels of implanted "matrigel"
      plugs. These results show that cell surface nucleolin is a specific marker of
      angiogenic endothelial cells within the vasculature. It may be a useful target
      molecule for diagnostic tests and drug delivery applications.

PMID- 14638863
TI  - Laminin gamma1 is critical for Schwann cell differentiation, axon myelination,
      and regeneration in the peripheral nerve.
AB  - Laminins are heterotrimeric extracellular matrix proteins that regulate cell
      viability and function. Laminin-2, composed of alpha2, beta1, and gamma1 chains,
      is a major matrix component of the peripheral nervous system (PNS). To
      investigate the role of laminin in the PNS, we used the Cre-loxP system to
      disrupt the laminin gamma1 gene in Schwann cells. These mice have dramatically
      reduced expression of laminin gamma1 in Schwann cells, which results in a similar
      reduction in laminin alpha2 and beta1 chains. These mice exhibit motor defects
      which lead to hind leg paralysis and tremor. During development, Schwann cells
      that lack laminin gamma1 were present in peripheral nerves, and proliferated and
      underwent apoptosis similar to control mice. However, they were unable to
      differentiate and synthesize myelin proteins, and therefore unable to sort and
      myelinate axons. In mutant mice, after sciatic nerve crush, the axons showed
      impaired regeneration. These experiments demonstrate that laminin is an essential
      component for axon myelination and regeneration in the PNS.

PMID- 14638865
TI  - Possible role of cell surface H+ -ATP synthase in the extracellular ATP synthesis
      and proliferation of human umbilical vein endothelial cells.
AB  - Extracellular ATP synthesis on human umbilical vein endothelial cells (HUVECs)
      was examined, and it was found that HUVECs possess high ATP synthesis activity on
      the cell surface. Extracellular ATP generation was detected within 5 s after
      addition of ADP and inorganic phosphate and reached a maximal level at 15 s. This
      type of ATP synthesis was almost completely inhibited by mitochondrial H(+)-ATP
      synthase inhibitors (e.g., efrapeptins, resveratrol, and piceatannol), which
      target the F(1) catalytic domain. Oligomycin and carbonyl cyanide m
      chlorophenylhydrazone, but not potassium cyanide, also inhibited extracellular
      ATP synthesis on HUVECs, suggesting that cell surface ATP synthase employs the
      transmembrane electrochemical potential difference of protons to synthesize ATP
      as well as mitochondrial H(+)-ATP synthase. The F(1)-targeting H(+)-ATP synthase
      inhibitors markedly inhibited the proliferation of HUVECs, but intracellular ATP
      levels in HUVECs treated with these inhibitors were only slightly affected, as
      shown by comparison with the control cells. Interestingly, piceatannol inhibited
      only partially the activation of Syk (a nonreceptor tyrosine kinase), which has
      been shown to play a role in a number of endothelial cell functions, including
      cell growth and migration. These findings suggest that H(+)-ATP synthase-like
      molecules on the surface of HUVECs play an important role not only in
      extracellular ATP synthesis but also in the proliferation of HUVECs. The present
      results demonstrate that the use of small molecular H(+)-ATP synthase inhibitors
      targeting the F(1) catalytic domain may lead to significant advances in potential
      antiangiogenic cancer therapies.

PMID- 14638864
TI  - Loss of proteolytically processed filaggrin caused by epidermal deletion of
      Matriptase/MT-SP1.
AB  - Profilaggrin is a large epidermal polyprotein that is proteolytically processed
      during keratinocyte differentiation to release multiple filaggrin monomer units
      as well as a calcium-binding regulatory NH2-terminal filaggrin S-100 protein. We
      show that epidermal deficiency of the transmembrane serine protease Matriptase/MT
      SP1 perturbs lipid matrix formation, cornified envelope morphogenesis, and
      stratum corneum desquamation. Surprisingly, proteomic analysis of Matriptase/MT
      SP1-deficient epidermis revealed the selective loss of both proteolytically
      processed filaggrin monomer units and the NH2-terminal filaggrin S-100 regulatory
      protein. This was associated with a profound accumulation of profilaggrin and
      aberrant profilaggrin-processing products in the stratum corneum. The data
      identify keratinocyte Matriptase/MT-SP1 as an essential component of the
      profilaggrin-processing pathway and a key regulator of terminal epidermal
      differentiation.

PMID- 14638866
TI  - Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies.
AB  - The WW domain containing oxidoreductase (WWOX) gene was recently identified as a
      candidate tumor suppressor gene at a common fragile site, FRA16D. Because the
      fragile histidine triad (FHIT) gene, a tumor suppressor gene encompassing the
      most active, common fragile site FRA3B, is frequently deleted in various cancers,
      we evaluated the expression of WWOX and FHIT in 74 cases of primary hematopoietic
      neoplasias and 20 leukemia cell lines. Aberration or absence of WWOX transcripts
      was detected in 51% of the primary cases and 55% of cell lines, and three WWOX
      nucleotide variants were detected among the leukemia cell lines. FHIT expression
      was absent or altered in 36% of the primary cases and 15% of cell lines. The
      occurrence of aberrant FHIT reverse transcription-PCR products correlated
      significantly with the occurrence of WWOX alterations. Wild-type transcripts of
      both genes were expressed in normal hematopoiesis along with a small fraction of
      short transcripts. A DNA blot study showed that WWOX and FHIT genes were deleted
      in 2 of 18 cases with primary acute leukemias; both genes were not expressed in
      the 2 cases. Furthermore, treatment of cells with a demethylating or histone
      acetylating agent in culture resulted in increased expression of WWOX and FHIT
      mRNA in leukemia cells. Conclusions are that WWOX expression is frequently
      altered or absent in hematopoietic disorders, often in association with FHIT
      alterations, and that alterations of these fragile genes may result not only from
      genomic deletions but also from epigenetic modifications associated with
      expression of fragility.

PMID- 14638867
TI  - Interaction and functional cooperation of the cancer-amplified transcriptional
      coactivator activating signal cointegrator-2 and E2F-1 in cell proliferation.
AB  - Activating signal cointegrator-2 (ASC-2), a novel coactivator, is amplified in
      several cancer cells and known to interact with mitogenic transcription factors,
      including serum response factor, activating protein-1, and nuclear factor-kappaB,
      suggesting the physiological role of ASC-2 in the promotion of cell
      proliferation. Here, we show that the expression pattern of ASC-2 was correlated
      with that of E2F-1 for protein increases at G(1) and S phase. Furthermore, cells
      stably overexpressing ASC-2 had an increased cell proliferation profile. These
      results prompted us to examine the functional interaction of ASC-2 and E2F-1.
      Biochemical evidence of protein interaction indicated that the transactivation
      domain of E2F-1 interacted with the COOH-terminal region of ASC-2. The importance
      of the E2F-1-ASC-2 interaction was supported by the demonstration that the
      coexpression of ASC-2 and E2F-1 synergistically transactivated E2F-1-driven gene
      transcription and the acetylation of E2F-1 protein was necessary for ASC-2
      mediated transcriptional coactivation. Interestingly, overexpression of ASC-2
      increased the endogenous protein level of E2F-1 in cells, resulting from the
      prolonged protein stability of E2F-1. Taken together, these results suggest that
      the cancer-amplified transcriptional coactivator ASC-2 may promote cell
      proliferation through enhancement of E2F-1-dependent transactivation of the
      expression of genes associated with cell cycle progression that may be available
      to favor tumor growth in vivo.

PMID- 14638868
TI  - Promotion of mitosis by activated protein kinase B after DNA damage involves polo
      like kinase 1 and checkpoint protein CHFR.
AB  - The role of the protein kinase B (PKB/Akt) in the regulation of cell survival and
      proliferation is well established. PKB is a key effector in the
      phosphatidylinositol 3-kinase pathway and plays a role in the initiation of S
      phase and in the G(2)-M transition. I report here that activated PKB shortens the
      G(2) arrest induced by DNA damage and promotes early entry into mitosis.
      Activated PKB supports high levels of expression and activity of the polo-like
      kinase 1 (Plk1) after DNA damage as cells accumulate in G(2). The checkpoint
      protein CHFR implicated in degradation of Plk1 is involved in the regulation of
      Plk1 by PKB. PKB phosphorylates CHFR in vitro and in vivo. Expression of a mutant
      form of CHFR that cannot be phosphorylated by PKB results in reduction of levels
      of Plk1 and inhibition of mitotic entry under normal conditions and after DNA
      damage. Results of this study support a model in which PKB facilitates mitotic
      resolution of DNA damage-induced G(2) arrest by inhibiting the checkpoint
      function of CHFR. The deregulated activation of PKB that occurs frequently in
      tumors might inhibit CHFR activity after DNA damage and therefore promote Plk1
      accumulation leading to the disruption of the DNA damage checkpoint.

PMID- 14638869
TI  - Erythropoietin promotes resistance against the Abl tyrosine kinase inhibitor
      imatinib (STI571) in K562 human leukemia cells.
AB  - Chronic myeloid leukemia is characterized by the Philadelphia chromosome
      translocation that causes expression of Bcr-Abl, a deregulated tyrosine kinase.
      Imatinib mesylate (STI571, Gleevec), a therapeutically used inhibitor of Bcr-Abl,
      causes apoptosis of Bcr-Abl-positive cells. In the leukemia cell line K562, we
      observed spontaneous resistance to imatinib at very low frequencies when cells
      were exposed to the drug (1 micro M) for more than 4 weeks. Surprisingly, in the
      presence of erythropoietin (Epo), K562 cells were temporarily able to sustain
      proliferation in the presence of imatinib, and imatinib-resistant clones could be
      isolated with high frequencies. From such imatinib-resistant, Epo-dependent
      clones, sublines could be established that were resistant to imatinib in the
      absence of Epo. Mitogen-activated protein (MAP) kinase activity was inhibited by
      imatinib treatment but could be partially restored by Epo. Inhibition of MAP
      kinase or phosphatidylinositol 3-kinase blocked the protective effect of Epo. The
      data suggest that K562 cells acquire factor dependency under imatinib/Epo
      treatment, allowing them to escape from imatinib-induced, immediate cell death.
      This pool of cells provides the basis for the outgrowth of imatinib-resistant
      clones of unlimited proliferative capacity. Thus, Epo, an endogenous regulator of
      hematopoiesis, promotes the development of resistance to imatinib.

PMID- 14638870
TI  - Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors.
AB  - While estrogen-related receptors (ERRalpha, ERRbeta, and ERRgamma) share a high
      amino acid sequence homology with estrogen receptors (ERs), estrogens are not
      ligands of ERRs. Structure-function studies from this and other laboratories have
      revealed that ERRs have small ligand-binding pockets and have provided evidence
      to show that these receptors can activate gene transcription in a constitutive
      manner. To address the question as to whether there is any agonist for ERRs, our
      laboratory recently performed virtual ligand screening on ERRalpha that predicted
      flavone and isoflavone phytoestrogens to be ligands of this receptor. Our
      mammalian cell transfection and mammalian two-hybrid experiments revealed that
      three isoflavones (genistein, daidzein, and biochanin A) and one flavone (6,3',4'
      trihydroxyflavone) behaved as agonists of ERRs. These phytoestrogens induced the
      activity of ERRalpha at concentrations that are comparable to those for the
      activation of ERalpha and ERbeta. In this study, we also used the results of
      ERRalpha ligand-binding site mutant, F232A, to verify our ERRalpha hypothetical
      computer model. Our recent ERR research has determined for the first time that
      flavone and isoflavone phytoestrogens are agonists of ERRs. In addition, our
      studies have demonstrated that an approach that combines structure-based virtual
      screening and receptor functional assays can identify novel ligands of orphan
      nuclear receptors.

PMID- 14638872
TI  - Developmental dyslexia.

PMID- 14638871
TI  - Mus81 endonuclease localizes to nucleoli and to regions of DNA damage in human S
      phase cells.
AB  - Mus81 is a highly conserved substrate specific endonuclease. Human Mus81 cleaves
      Holliday junctions, replication forks, and 3' flap substrates in vitro,
      suggesting a number of possible in vivo functions. We show here that the
      abundance of human Mus81 peaks in S-phase and remains high in cells that have
      completed DNA replication and that Mus81 is a predominantly nuclear protein, with
      super accumulation in nucleoli. Two RecQ related DNA helicases BLM and WRN that
      are required for recombination repair in human cells colocalize with Mus81 in
      nucleoli. However, the nucleolar retention of Mus81 is not dependent on the
      presence of BLM or WRN, or on ongoing transcription. Mus81 is recruited to
      localized regions of UV damage in S-phase cells, but not in cells that are
      blocked from replicating DNA or that have completed replication. The retention of
      human Mus81 at regions of UV-induced damage specifically in S-phase cells suggest
      that the enzyme is recruited to the sites at which replication forks encounter
      damaged DNA. The nucleolar concentration of Mus81 suggests that it is required to
      repair problems that arise most frequently in the highly repetitive nucleolar
      DNA. Together these data support a role for Mus81 in recombination repair in
      higher eukaryotes.

PMID- 14638873
TI  - Surgical treatment of ruptured intracranial aneurysms.

PMID- 14638874
TI  - Why study mesial temporal atrophy in patients with intractable temporal lobe
      epilepsy?

PMID- 14638875
TI  - Neurogenetics: single gene disorders.
AB  - The advent of molecular biology has changed the way in which neurological
      illnesses are classified, and the single genes causing a number of disorders have
      been identified. In addition, techniques such as linkage analysis and DNA
      sequencing have resulted in greater understanding of multi-gene diseases. This
      review covers some of the molecular tools and animal models used for genetic
      analysis and for DNA based diagnosis, and a brief survey of information available
      on the internet.

PMID- 14638877
TI  - Evaluation of the modifying effects of unfavourable genotypes on classical
      clinical risk factors for ischaemic stroke.
AB  - OBJECTIVES: Ischaemic stroke is a frequent heterogeneous multifactorial disease
      that is affected by a number of genetic mutations and environmental factors. We
      hypothesised the clinical importance of the interactions between common,
      unfavourable genetic mutations and clinical risk factors in the development of
      ischaemic stroke. METHODS: The Factor V Leiden G1691A (Leiden V), the prothrombin
      G20210A, the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations,
      the angiotensin converting enzyme I/D (ACE I/D), and apolipoprotein allele e4
      (APO e4) genotypes were examined by the polymerase chain reaction (PCR) technique
      in 867 ischaemic stroke patients and 743 healthy controls. Logistic regression
      models were used to estimate the roles of the co-occurrences of the clinical risk
      factors and common genetic mutations in ischaemic stroke. RESULTS: The Leiden V
      mutation in combination with hypertension or diabetes mellitus increased the risk
      of ischaemic stroke. We found synergistic effects between the ACE D/D and MTHFR
      677TT genotypes and drinking or smoking. The presence of the APO e4 greatly
      facilitated the unfavourable effects of hypertension, diabetes mellitus, smoking,
      or drinking on the incidence of ischaemic stroke. CONCLUSION: In certain
      combinations, pairing of common unfavourable genetic factors, which alone confer
      only minor or non-significant risk, with clinical risk factors can greatly
      increase the susceptibility to ischaemic stroke.

PMID- 14638878
TI  - Heralding manifestations of basilar artery occlusion with lethal or severe
      stroke.
AB  - BACKGROUND: Basilar artery occlusion usually causes severe disability or death.
      Until the recent developments in local intra-arterial or systemic intravenous
      fibrinolysis, interest in early diagnosis was low because there was no
      satisfactory treatment. Thus there is little information about the initial phase
      of the disease. OBJECTIVE: To report on the early clinical features and patterns
      of evolution of severe symptomatic basilar artery occlusion. METHODS: 24 patients
      with established basilar artery occlusion (confirmed by angiography or at
      necropsy) were reviewed retrospectively, focusing on the early clinical aspects
      and time course of the disease. RESULTS: The most common initial symptoms were
      motor deficits (16/24, including facial palsies), articulatory speech
      difficulties (15/24), vertigo, nausea or vomiting (13/24), and headaches (10/24).
      The most frequent objective initial findings were motor deficits (22/24), facial
      palsies (19/24), eye movement abnormalities (15/24), lower cranial nerve deficits
      (15/24), altered level of consciousness (12/24), and bilateral extensor plantar
      responses (9/24). Onset of the disease was gradual in nearly all patients and in
      half the warning signs were present for up to two months before the final stage.
      Headaches and visual disturbances were early signs, while speech difficulties and
      motor deficits were late signs. Once permanent neurological deficits were
      present, the final illness was reached within six hours in 41%, between six and
      24 hours in 32%, and in two to three days in 27%. CONCLUSIONS: All the patients
      reviewed presented some symptoms and signs pointing to brain stem involvement.
      Only 8% (2/24) had an acute course with no adequate warning signs.

PMID- 14638879
TI  - Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy.
AB  - OBJECTIVE: The objective of this study was to assess the volumes of medial
      temporal lobe structures using high resolution magnetic resonance images from
      patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS:
      We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and
      unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1
      mm isotropic voxels, and applied a field non-homogeneity correction and a linear
      stereotaxic transformation into a standard space. The structures of interest are
      the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar
      cortex, hippocampus, and amygdala. Structures were identified by visual
      examination of the coronal, sagittal, and axial planes. The threshold of
      statistical significance was set to p<0.05. RESULTS: Patients with right and left
      MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal
      (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients
      with right MTLE exhibited a significant asymmetry of all studied structures; the
      right hemisphere structures had smaller volume than their left side counterparts.
      We did not observe linear correlations between the volumes of different
      structures of the medial temporal lobe in patients with MTLE. CONCLUSION:
      Patients with refractory MTLE have damage in the temporal lobe that extends
      beyond the hippocampus, and affects the regions with close anatomical and
      functional connections to the hippocampus.

PMID- 14638880
TI  - MRI directed bilateral stimulation of the subthalamic nucleus in patients with
      Parkinson's disease.
AB  - OBJECTIVE: Bilateral chronic high frequency deep brain stimulation (DBS) of the
      subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with
      advanced Parkinson's disease refractory to medical therapy. Advances in
      neuroimaging and neurophysiology have led to the development of varied targeting
      methods for the delivery of this treatment. Intraoperative neurophysiological and
      clinical monitoring is regarded by many to be mandatory for accurate STN
      localisation. We have examined efficacy of bilateral STN stimulation using a
      predominantly magnetic resonance imaging (MRI)-directed technique. METHODS: DBS
      leads were stereotactically implanted into the STN using an MRI directed method,
      with intraoperative macrostimulation used purely for adjustment. The effects of
      DBS were evaluated in 16 patients followed up to 12 months, and compared with
      baseline assessments. Assessments were performed in both off and on medication
      states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS)
      and timed motor tests. Functional status outcomes were examined using the PDQ-39
      quality of life questionnaire. A battery of psychometric tests was used to assess
      cognition. RESULTS: After 12 months, stimulation in the off medication state
      resulted in significant improvements in Activities of Daily Living and Motor
      scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests
      were significantly improved in the off medication state. Motor scores (UPDRS part
      III) were significantly improved by 40% in the on medication state. Dyskinesias
      and off duration were significantly reduced and the mean dose of L-dopa
      equivalents was reduced by half. Psychometric test scores were mostly unchanged
      or improved. Adverse events were few. CONCLUSIONS: An MRI directed targeting
      method for implantation of DBS leads into the STN can be used safely and
      effectively, and results are comparable with studies using intraoperative
      microelectrode neurophysiological targeting. In addition, our method was
      associated with an efficient use of operating time, and without the necessary
      costs of microelectrode recording.

PMID- 14638881
TI  - A population based epidemiological study on myasthenia gravis in Estonia.
AB  - OBJECTIVE: To describe the occurrence of myasthenia gravis in the Baltic area.
      METHODS: Data were obtained from hospital files recorded during the period 1942
      to 1996 from neurologists and the patient organisation. Survival data were
      checked with the Estonian Citizenship and Migration Board. Prevalence was
      determined on 1 January 1997. A questionnaire on the course of myasthenia gravis
      was sent to all the prevalent patients. RESULTS: The size of the population
      surveyed was 1 462 130. The average annual incidence from 1970 to 1996 was 4.0
      per million (women, 5.2; men, 2.6). The point prevalence was 99 per million
      (women, 133; men 59). The incidence in the younger age group (<50 years) was 3.4
      per million (women, 4.8; men, 1.9) and in the older age group (>or=50 years), 5.5
      (women, 5.9; men, 4.9). The prevalence ratio was twofold higher in the older age
      group (p<0.0001)-for men (p = 0.034) as well as for women (p<0.001). CONCLUSIONS:
      Prevalence and incidence values of myasthenia gravis from Estonia are similar to
      those reported in most studies from Europe and north America. However, there
      seems to be a higher frequency in the elderly (>or=50 years) in Estonia.

PMID- 14638882
TI  - Ulcus terebrans: an unusual cause of paraparesis.

PMID- 14638883
TI  - Auditory disturbance as a prodrome of anterior inferior cerebellar artery
      infarction.
AB  - OBJECTIVES: To investigate the clinical and radiological features of patients
      presenting with an acute auditory syndrome as a prodromal symptom of anterior
      inferior cerebellar artery (AICA) infarction. METHODS: 16 consecutive cases of
      AICA infarction diagnosed by brain magnetic resonance imaging completed a
      standardised audiovestibular questionnaire and underwent a neuro-otological
      evaluation by an experienced neuro-otologist. RESULTS: Five patients (31%) had an
      acute auditory syndrome as a prodrome of AICA infarction one to 10 days before
      onset of other brain stem or cerebellar symptoms. Two types of acute auditory
      syndrome were found: recurrent transient hearing loss with or without tinnitus (n
      = 3), and a single episode of prolonged hearing loss with or without tinnitus (n
      = 2). The episodic symptoms were brief, lasting only minutes. The tinnitus
      preceding the infarction was identical to the tinnitus experienced at the time of
      infarction. At the time of infarction, all patients developed hearing loss,
      tinnitus, vertigo, and ipsilateral hemiataxia. The most commonly affected site
      was the middle cerebellar peduncle (n = 5). Four of the five patients had
      incomplete hearing loss and all had absence of vestibular function to caloric
      stimulation on the affected side. CONCLUSIONS: Acute auditory syndrome may be a
      warning sign of impending pontocerebellar infarction in the distribution of the
      AICA. The acute auditory syndrome preceding an AICA infarct may result from
      ischaemia of the inner ear or the vestibulocochlear nerve.

PMID- 14638884
TI  - Magnetoencephalographic representation of the sensorimotor hand area in cases of
      intracerebral tumour.
AB  - OBJECTIVE: To assess the clinical value of magnetoencephalography (MEG) in
      localising the primary hand motor area and evaluating cortical distortion of the
      sensorimotor cortices in patients with intracerebral tumour. METHODS: 10 normal
      volunteers (controls) and 14 patients with an intracerebral tumour located around
      the central region were studied. Somatosensory evoked magnetic fields (SEFs)
      following median nerve stimulation, and movement related cerebral magnetic fields
      (MRCFs) following index finger extension, were measured in all subjects and
      analysed by the equivalent current dipole (ECD) method to ascertain the neuronal
      sources of the primary sensory and motor components (N20m and MF, respectively).
      These ECD locations were defined as the primary hand sensory and motor areas and
      the positional relations between these two functional areas in controls and
      patients were investigated. RESULTS: The standard range of ECD locations of MF to
      N20m was determined in controls. In 11 of the 14 patients, MRCFs could identify
      the primary motor hand area. ECD locations of MF were significantly closer to the
      N20m in the medial-lateral direction in patients than in controls. In patients
      with a tumour located below the sensorimotor hand area, relative ECD locations of
      MF to N20m moved anteriorly over the standard range determined in the control
      subjects. These MEG findings correlated well with radiological tumour locations.
      The mean estimated ECD strength of MF was significantly lower in patients than in
      controls. CONCLUSIONS: MRCF was useful in localising the primary motor hand area
      in patients with intracerebral tumour. The relative ECD locations of MF to N20m
      describe the anatomical distortion of the sensorimotor cortex.

PMID- 14638885
TI  - Pyridostigmine in postpolio syndrome: no decline in fatigue and limited
      functional improvement.
AB  - OBJECTIVES: To investigate the effect of pyridostigmine on fatigue, physical
      performance, and muscle function in subjects with postpoliomyelitis syndrome.
      METHODS: 67 subjects with increased fatigue and new weakness in one quadriceps
      muscle showing neuromuscular transmission defects, were included in a randomised,
      double blind, placebo controlled trial of 60 mg pyridostigmine four times a day
      for 14 weeks. Primary outcome was fatigue (on the "energy" category of the
      Nottingham health profile). Secondary outcomes included two minute walking
      distance and quadriceps strength and jitter. Motor unit size of the quadriceps
      was studied as a potential effect modifier. The primary data analysis compared
      the changes from baseline in the outcomes in the last week of treatment between
      groups. RESULTS: 31 subjects treated with pyridostigmine and 31 subjects treated
      with placebo completed the trial. No significant effect of pyridostigmine was
      found on fatigue. The walking distance improved more in the pyridostigmine group
      than in the placebo group (by 7.2 m (6.0%); p<0.01). Subgroup analysis showed
      that a significant improvement in walking performance was only found in subjects
      with normal sized motor units. Quadriceps strength improved more in the
      pyridostigmine group than in the placebo group (by 6.7 Nm (7.2%); p = 0.15). No
      effect of pyridostigmine was found on jitter. CONCLUSIONS: Pyridostigmine in the
      prescribed dose did not reduce fatigue in subjects with postpoliomyelitis
      syndrome. However, it may have a limited beneficial effect on physical
      performance, especially in subjects with neuromuscular transmission defects in
      normal sized motor units.

PMID- 14638886
TI  - Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting.
AB  - BACKGROUND: The high pressures documented in the intracranial venous sinuses in
      idiopathic intracranial hypertension (IIH) could be the result of focal stenotic
      lesions in the lateral sinuses obstructing cranial venous outflow. OBJECTIVE: To
      explore the relation between venous sinus disease and IIH. METHODS: 12 patients
      with refractory IIH had dilatation and stenting of the venous sinuses after
      venography and manometry had shown intracranial venous hypertension proximal to
      stenoses in the lateral sinuses. Intrasinus pressures were recorded before and
      after the procedure and correlated with clinical outcome. RESULTS: Intrasinus
      pressures were variably reduced by stenting. Five patients were rendered
      asymptomatic, two were improved, and five were unchanged. CONCLUSIONS: The
      importance of venous sinus disease in the aetiology of IIH is probably
      underestimated. Lateral sinus stenting shows promise as an alternative treatment
      to neurosurgical intervention in intractable cases.

PMID- 14638887
TI  - CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other
      hypersomnias and neurological conditions.
AB  - OBJECTIVE: To determine the role of CSF hypocretin-1 in narcolepsy with and
      without cataplexy, Kleine-Levin syndrome (KLS), idiopathic and other
      hypersomnias, and several neurological conditions. PATIENTS: 26 narcoleptic
      patients with cataplexy, 9 narcoleptic patients without cataplexy, 2 patients
      with abnormal REM-sleep-associated hypersomnia, 7 patients with idiopathic
      hypersomnia, 2 patients with post-traumatic hypersomnia, 4 patients with KLS, and
      88 patients with other neurological disorders. RESULTS: 23 patients with
      narcolepsy-cataplexy had low CSF hypocretin-1 levels, while one patient had a
      normal hypocretin level (HLA-DQB1*0602 negative) and the other two had
      intermediate levels (familial forms). One narcoleptic patient without cataplexy
      had a low hypocretin level. One patient affected with post-traumatic hypersomnia
      had intermediate hypocretin levels. The KLS patients had normal hypocretin levels
      while asymptomatic, but one KLS patient (also affected with Prader-Willi
      syndrome) showed a twofold decrease in hypocretin levels during a symptomatic
      episode. Among the patients without hypersomnia, two patients with normal
      pressure hydrocephalus and one with unclear central vertigo had intermediate
      levels. CONCLUSION: Low CSF hypocretin-1 is highly specific (99.1%) and sensitive
      (88.5%) for narcolepsy with cataplexy. Hypocretin ligand deficiency appears not
      to be the major cause for other hypersomnias, with a possible continuum in the
      pathophysiology of narcolepsy without cataplexy and idiopathic hypersomnia.
      However, partial hypocretin lesions without low CSF hypocretin-1 consequences
      cannot be definitely excluded in those disorders. The existence of normal
      hypocretin levels in narcoleptic patients and intermediate levels in other rare
      aetiologies needs further investigation, especially for KLS, to establish the
      functional significance of hypocretin neurotransmission alterations.

PMID- 14638888
TI  - Clinical surveillance of carpal tunnel syndrome in two areas of the United
      Kingdom, 1991-2001.
AB  - OBJECTIVE: To study the demographic characteristics of patients with carpal
      tunnel syndrome and changes in incidence over time. METHODS: Prospective
      collection of neurophysiological and clinical data on all patients presenting to
      the subregional department of clinical neurophysiology in Canterbury, UK, from
      1992 to 2001 and to the electromyography clinic in St Luke's Hospital,
      Huddersfield, UK, from 1991 to 1993. RESULTS: 6245 new cases of
      neurophysiologically confirmed carpal tunnel syndrome were identified in
      Canterbury and 590 in Huddersfield. The average annual incidences (per 100,000)
      were 139.4 for women and 67.2 for men in East Kent, and 83.2 for women and 48.0
      for men in Huddersfield. Corrected to the WHO European standard population these
      rates were 120.5 for women and 60.0 for men in East Kent, and 61.5 for women and
      35.0 for men in Huddersfield. Between 1992 and 2001 there was an increase in the
      number of confirmed cases in East Kent but a decrease in their average severity.
      The age distributions were bimodal with a peak in the 50-54 age group and a
      second peak between 75 and 84 years. Over half the cases were bilateral. The
      disorder was consistently worse in the elderly, and more severe in men than in
      women in all age groups. CONCLUSIONS: The age distributions of unselected cases
      of carpal tunnel syndrome in both clinics differ markedly from that usually
      portrayed in surgical series. There was a significant increase in cases diagnosed
      between 1992 and 2001 in Canterbury, probably the result of increased
      ascertainment of milder cases. Median nerve impairment is more severe in the
      elderly and in men at all ages.

PMID- 14638889
TI  - Ruptured intracranial aneurysms: the outcome of surgical treatment in experienced
      hands in the period prior to the advent of endovascular coiling.
AB  - OBJECTIVES: To evaluate the results of treatment of patients with a ruptured
      intracranial aneurysm treated by a single experienced vascular neurosurgeon in
      the period prior to the introduction of endovascular coiling. METHODS: Over a
      mean (SD) period of 9 (2) years, between January 1990 and June 1999, 245
      consecutive patients with ruptured intracranial aneurysms were treated. Patients'
      details were obtained from a database that had been constructed prospectively.
      The patients consisted of all those patients treated by the senior author (Mr
      Maurice-Williams) over this period-that is, every third day on call at his unit.
      During this period, all patients under the age of 75 years with a diagnosis of
      subarachnoid haemorrhage were admitted to the neurosurgical unit as soon as was
      practicable regardless of clinical grade. RESULTS: Of 245 patients, 190 (77.6%)
      underwent treatment by open surgery using standard microsurgical techniques. At 1
      year, the mortality of the operated patients was 2.6%, while 89.5% of the
      patients had a Glasgow Outcome Score (GOS) of 4 and 5. The overall management
      outcome (all patients treated, including operated and non-operated cases) at 1
      year was: 17.1 % dead while 74.3% had GOS 4 and 5. Of the 190 patients who
      underwent surgery, 38 (20%) required additional operations, totalling 72
      operations in all. Of these, 32 were for hydrocephalus and 17 for the evacuation
      of intracranial haematomas/collections. Complications of surgery occurred in 56
      patients (29.5%). CONCLUSION: Open surgery, despite good eventual results, is
      associated with a significant rate of re-operations and complications that would
      probably be largely avoided with endovascular treatment. Nevertheless, although
      endovascular coiling has these immediate advantages over surgery it is still not
      certain that the long term results will be superior to surgery which leads to
      permanent obliteration of the aneurysm. There may still be a need for open
      surgery in the future.

PMID- 14638891
TI  - Trigeminal neuralgia (Fothergill's disease) in the 17th and 18th centuries.

PMID- 14638890
TI  - Limitations of sniff nasal pressure in patients with severe neuromuscular
      weakness.
AB  - BACKGROUND: Inspiratory muscle strength in patients with neuromuscular disorders
      can be assessed using sniff inspiratory nasal pressure (Pn(sn)) and maximum
      inspiratory mouth pressure (PI(max)). However, the relative merits of Pn(sn)
      against PI(max) are not known in patients with severe neuromuscular disease.
      OBJECTIVE: To investigate whether severity of disease modifies the relation
      between Pn(sn) and PI(max). METHODS: Vital capacity (VC), Pn(sn), and PI(max)
      were measured in 258 patients with neuromuscular disorders. RESULTS: Data were
      analysed from 241 patients, 17 being unable to perform PI(max) or Pn(sn)
      manoeuvres. The correlation between Pn(sn) and PI(max) was +0.94 (p<0.0001), with
      a mean (SD) difference between Pn(sn) and PI(max) of -4.8 (21.2) cm H(2)O (the
      limits of agreement were 37.6 and -47.2 cm H(2)O). VC (% predicted) was
      positively correlated with Pn(sn)/PI(max) (r = +0.86; p<0.0001), with a lower
      Pn(sn)/PI(max) value in patients with a VC <40% of predicted than in those with a
      VC >40% (0.80 (0.35) v 1.04 (0.41); p<0.0001). CONCLUSIONS: PI(max) is greater
      than Pn(sn) in patients with a severe restrictive ventilatory defect caused by
      neuromuscular disease. Pn(sn) may not accurately reflect inspiratory muscle
      strength in such patients and it is thus advisable to use both tests.

PMID- 14638892
TI  - A post-marketing study on interferon beta 1b and 1a treatment in relapsing
      remitting multiple sclerosis: different response in drop-outs and treated
      patients.
AB  - BACKGROUND: Interferon beta 1b (Betaferon) and 1a (Avonex) were licensed in Italy
      for treating relapsing-remitting multiple sclerosis in February 1996 and August
      1997, respectively. OBJECTIVES: To evaluate the effectiveness of these agents on
      the basis of clinical experience in northern Italian multiple sclerosis centres.
      DESIGN: Clinical data on patients with relapsing-remitting multiple sclerosis
      were collected on an appropriate form from 65 centres in northern Italy.
      Intention to treat analysis was not possible, so patients who discontinued
      treatment (drop-outs) and who continued treatment (treated) were analysed
      separately. The main outcome measures were annual relapse frequency, number of
      relapse-free patients, mean change in extended disability status scale score
      (EDSS), and number of patients who worsened. RESULTS: 1481 patients were
      included; 834 were treated with Betaferon and 647 with Avonex for mean periods of
      21.4 and 12.0 months, respectively. Basal EDSS was 2.37 and 2.17, respectively,
      and relapse frequency was 1.62 and 1.45. The annual relapse rate decreased by
      more than 60% with Betaferon and 55% with Avonex. The proportions of relapse
      free, improved, and worsened patients were similar in the two groups. More
      patients interrupted treatment with Betaferon (41.1%) than with Avonex (15.3%);
      such patients showed more active disease at baseline and during treatment. The
      incidence of side effects was higher in Betaferon treated patients. CONCLUSIONS:
      The effectiveness of Betaferon and Avonex is confirmed. There was a more marked
      effect than expected from the experimental trial results. This might reflect
      differences in inclusion criteria, or, more likely, loss of drop-outs, favouring
      selective retention of responders.

PMID- 14638893
TI  - Diffuse brain oedema in idiopathic intracranial hypertension: a quantitative
      magnetic resonance imaging study.
AB  - OBJECTIVES: To investigate the hypothesis that idiopathic intracranial
      hypertension is associated with diffuse brain oedema, using quantitative magnetic
      resonance imaging. METHODS: Values for the mean diffusivity of water (<D>) and
      the proton longitudinal relaxation time (T1) were measured for various brain
      regions in 10 patients with idiopathic intracranial hypertension and 10 age, sex,
      and weight matched controls. RESULTS: No significant differences in <D> and T1
      values were found between patient and control groups in any of the brain regions
      investigated. CONCLUSIONS: The results suggest that idiopathic intracranial
      hypertension is not associated with abnormalities of convective transependymal
      water flow leading to diffuse brain oedema.

PMID- 14638894
TI  - An unusual phenotype of McLeod syndrome with late onset axonal neuropathy.

PMID- 14638895
TI  - Isolated total tongue paralysis as a manifestation of bilateral medullary
      infarction.

PMID- 14638896
TI  - NHS direct for headache.

PMID- 14638899
TI  - Genetic features of mitochondrial respiratory chain disorders.
AB  - Oxidative phosphorylation, i.e., ATP synthesis by the oxygen-consuming
      respiratory chain (RC), supplies most organs and tissues with a readily usable
      energy source, being functional before birth. Consequently, RC deficiencies can
      theoretically give rise to any symptom, in any organ or tissue, at any age and
      with any mode of inheritance, because of the twofold genetic origin of RC
      components (nuclear DNA and mitochondrial DNA). It was long wrongly considered
      that RC disorders originate from mutations of mitochondrial DNA, because for a
      long time only mutations or deletions of mitochondrial DNA were identified.
      However, the number of known disease-causing mutations in nuclear genes is
      steadily growing. These genes encode the various subunits of each complex,
      ancillary proteins functioning at different stages of holoenzyme biogenesis,
      including transcription, translation, chaperoning, addition of prosthetic groups,
      and protein assembly, and various enzymes involved in mitochondrial DNA
      metabolism.

PMID- 14638900
TI  - Albumin regulates the Na+/H+ exchanger 3 in OKP cells.
AB  - Albumin filtered by the glomerulus is reabsorbed in the proximal tubule. We have
      shown previously that proteinuria stimulates the proximal tubular Na(+)/H(+)
      exchanger 3 (NHE3) in rats. Activation of NHE3 may be a pathophysiologically
      important factor in the development of renal salt and water retention observed in
      the nephrotic syndrome. For examining whether albumin is a specific inducer of
      proximal tubular Na(+)/H(+) exchange and to determine the molecular mechanisms by
      which it regulates Na(+)/H(+) exchange, the effect of albumin on NHE3 in opossum
      kidney cells was studied. Albumin activated Na(+)/H(+) exchange in a time- and
      dose-dependent manner up to 100% in 48 h. In the early phase of stimulation (2 to
      12 h), NHE3 activity was increased without changes in NHE3 protein and mRNA. At
      24 h, increased NHE3 activity was accompanied by increase in cell surface NHE3
      protein. The increase in surface NHE3 was associated with increased bidirectional
      trafficking of NHE3 protein between intracellular compartments and the cell
      surface. At 48 h, total cell NHE3 protein abundance and mRNA were increased as
      well. Whereas NHE3 translation was increased, NHE3 protein half-life remained
      unchanged. The effects of albumin on NHE3 protein abundance were modified by
      hydrocortisone in a complicated pattern. These results indicate that albumin
      directly regulates proximal tubular NHE3 at multiple levels.

PMID- 14638901
TI  - Short-term regulation of basolateral organic anion uptake in proximal tubular
      opossum kidney cells: prostaglandin E2 acts via receptor-mediated activation of
      protein kinase A.
AB  - It was shown previously that EGF induces release of the important prostanoid
      prostaglandin E(2) (PGE(2)) in proximal tubular opossum kidney (OK) cells and
      PGE(2) then stimulates initial basolateral uptake of organic anions (OA) dose
      dependently. PGE(2) is a receptor agonist and a known substrate for the
      basolateral exchanger mediating OA uptake (OAT1 and/or OAT3). This study
      investigated the mechanism of short-term PGE(2) action on initial basolateral OA
      uptake in OK cells. PGE(2) stimulation of OA uptake was abolished by selective
      inhibition of adenylate cyclase (by MDL-12, 330A) or protein kinase A (PKA; by
      H89). PGE(2) stimulation of OA uptake persisted after preloading the cells with
      glutarate and was still abolished by inhibition of PKA. Selective activation of
      adenylate cyclase by forskolin led to identical results. These data contradicted
      the hypothesis that PGE(2) action on OA uptake is due to its action as a counter
      ion. Therefore, we tested whether the PGE(2) receptors (EP1 to 4) are involved in
      stimulation of OA uptake in OK cells by PGE(2). Because of their intracellular
      signaling profile, EP1 and EP3 were not taken into account as possible receptors
      for mediation of PGE(2)-induced OA uptake. With the use of selective agonists (11
      deoxy PGE(1) and butaprost), EP4 was pharmacologically identified as the receptor
      responsible for PGE(2)-mediated stimulation of OA uptake. By reverse
      transcription-PCR, cloning, and subsequent sequencing, a homologue fragment to
      EP4 was identified in OK cells. EGF-induced stimulation of basolateral organic
      anion uptake was abolished by inhibition of adenylate cyclase or PKA. This
      indicates that EGF action is mediated by generation of PGE(2). The following
      model is proposed: PGE(2) generated in the cells does not act as a counter ion
      but activates adenylate cyclase. This is mediated by a homologue of EP4 receptor.
      cAMP then activates PKA, which stimulates initial basolateral uptake of OA in OK
      cells by a not-yet-known mechanism. PGE(2) is an organic anion, a potential
      stimulator of organic anion excretion, and an important mediator of inflammation
      all at once. Thus, the mechanism presented here may contribute to a limitation of
      inflammatory events in the kidney cortex interstitium.

PMID- 14638902
TI  - Localization and regulation of the ATP6V0A4 (a4) vacuolar H+-ATPase subunit
      defective in an inherited form of distal renal tubular acidosis.
AB  - Vacuolar-type H(+)-ATPases (V-H(+)-ATPases) are the major H(+)-secreting protein
      in the distal portion of the nephron and are involved in net H(+) secretion
      (bicarbonate generation) or H(+) reabsorption (net bicarbonate secretion). In
      addition, V-H(+)-ATPases are involved in HCO(3)(-) reabsorption in the proximal
      tubule and distal tubule. V-H(+)-ATPases consist of at least 13 subunits, the
      functions of which have not all been elucidated. Mutations in the accessory
      ATP6V0A4 (a4 isoform) subunit have recently been shown to cause an inherited form
      of distal renal tubular acidosis in humans. Here, the localization of this
      subunit in human and mouse kidney was studied and the regulation of expression
      and localization of this subunit in mouse kidney in response to acid-base and
      electrolyte intake was investigated. Reverse transcription-PCR on dissected mouse
      nephron segments amplified a4-specific transcripts in proximal tubule, loop of
      Henle, distal convoluted tubule, and cortical and medullary collecting duct. a4
      protein was localized by immunohistochemistry to the apical compartment of the
      proximal tubule (S1/S2 segment), the loop of Henle, the intercalated cells of the
      distal convoluted tubule, the connecting segment, and all intercalated cells of
      the entire collecting duct in human and mouse kidney. All types of intercalated
      cells expressed a4. NH(4)Cl or NaHCO(3) loading for 24 h, 48 h, or 7 d as well as
      K(+) depletion for 7 and 14 d had no influence on a4 protein expression levels in
      either cortex or medulla as determined by Western blotting. Immunohistochemistry,
      however, demonstrated a subcellular redistribution of a4 in response to the
      different stimuli. NH(4)Cl and K(+) depletion led to a pronounced apical staining
      in the connecting segment, cortical collecting duct, and outer medullary
      collecting duct, whereas NaHCO(3) loading caused a stronger bipolar staining in
      the cortical collecting duct. Taken together, these results demonstrate a4
      expression in the proximal tubule, loop of Henle, distal tubule, and collecting
      duct and suggest that under conditions in which increased V-H(+)-ATPase activity
      is required, a4 is regulated by trafficking but not protein expression. This may
      allow for the rapid adaptation of V-H(+)-ATPase activity to altered acid-base
      intake to achieve systemic pH homeostasis. The significance of a4 expression in
      the proximal tubule in the context of distal renal tubular acidosis will require
      further clarification.

PMID- 14638903
TI  - Dimeric architecture of the human bumetanide-sensitive Na-K-Cl Co-transporter.
AB  - The primary mediator of NaCl reabsorption in the renal distal tubule is the human
      bumetanide-sensitive Na(+)-K(+)-2Cl(-) co-transporter (hNKCC2), located at the
      apical membrane of the thick ascending limb of Henle's loop. The physiologic
      importance of this transporter is emphasized by the tubular disorder Bartter
      syndrome type I, which arises from the functional impairment of hNKCC2 as a
      result of mutations in the SLC12A1 gene. The aim of the present study was to
      investigate the oligomeric state of hNKCC2 to understand further its operational
      mechanism. To this end, hNKCC2 was heterologously expressed in Xenopus laevis
      oocytes. Chemical cross-linking with dimethyl-3,3-dithio-bis-propionamidate
      indicated that hNKCC2 subunits can reversibly form high molecular weight
      complexes. Co-immunoprecipitation of tagged hNKCC2 subunits further substantiated
      a physical interaction between individual hNKCC2 subunits. The size of the hNKCC2
      multimers was determined by sucrose gradient centrifugation, and a preference for
      dimeric complexes (approximately 320 kD) was demonstrated. Finally, concatemeric
      constructs consisting of two wild-type subunits or a wild-type and a functionally
      impaired hNKCC2 subunit (G319R) were expressed in oocytes. Subsequently, the
      concatemers were functionally characterized, resulting in a significant
      bumetanide-sensitive (22)Na(+) uptake of 2.5 +/- 0.2 nmol/oocyte per 30 min for
      the wild-type-wild-type concatemer, which was reduced to 1.3 +/- 0.1 nmol/oocyte
      per 30 min for the wild-type-G319R concatemer. In conclusion, this study suggests
      that hNKCC2 forms at least functional dimers when expressed in Xenopus laevis
      oocytes of which the individual subunits transport Na(+) independently.

PMID- 14638904
TI  - Hepatocyte growth factor modulates matrix metalloproteinases and plasminogen
      activator/plasmin proteolytic pathways in progressive renal interstitial
      fibrosis.
AB  - Evidence suggests that hepatocyte growth factor (HGF) ameliorates renal fibrosis
      in animal models of chronic renal disease by promoting extracellular matrix
      catabolism. This study examined the molecular mechanisms of HGF-induced
      alterations in matrix degradation both in vitro and in vivo. In vitro, HGF
      increased the collagen catabolizing activity of human proximal tubular epithelial
      cells (HKC) that were treated with TGF-beta1. Increased collagen catabolism was
      associated with enhanced activity of both matrix metalloproteinases (MMP) and
      plasminogen activators (PA)/plasmin proteolytic pathways. HGF abrogated TGF-beta1
      induced production of the profibrotic tissue inhibitor of metalloproteinase-2
      (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1). In addition, HGF induced
      the production of MMP-9. In vivo, continuous infusion of HGF in the rat remnant
      kidney model ameliorated renal fibrosis and tubulointerstitial collagen
      deposition. This was associated with increased tubular expression of MMP-9,
      enhanced in situ gelatinolytic activity, partially restored plasmin activity and
      decreased expression of TIMP-2 and PAI-1 in tubular cells, and upregulation of
      renal TIMP-3 expression. Conversely, blocking of endogenous HGF by an anti-HGF
      neutralizing antibody increased renal fibrosis and interstitial collagen. This
      was accompanied by decreased tubular expression of MMP-9, less in situ
      proteolytic activity, and elevated expression of TIMP-2 and PAI-1 in tubular
      cells. Collectively, these findings demonstrate that HGF ameliorates renal
      fibrosis by enhancing extracellular matrix catabolism via both MMP and the
      PA/plasmin proteolytic pathways.

PMID- 14638905
TI  - Increased renal vascular endothelial growth factor and angiopoietins by
      angiotensin II infusion is mediated by both AT1 and AT2 receptors.
AB  - A link between angiotensin II and cell proliferation has previously been
      reported. However, there remains controversy as to the role of the individual
      angiotensin II receptor subtypes in mediating these effects and their link to
      angiogenic cytokines and their receptors. Male Sprague-Dawley rats were infused
      with either angiotensin II or vehicle for 14 d at a dose of 58.3 ng/min.
      Angiotensin II-infused rats received no treatment, an AT(1) receptor antagonist
      valsartan (30 mg/kg per d), or an AT(2) receptor antagonist PD123319 (830
      ng/min). Gene expression of vascular endothelial growth factor (VEGF) and
      receptor VEGF-R2, as well as Tie-2 and its ligands angiopoietin-1 (Ang-1) and
      angiopoietin-2 (Ang-2) were assessed by reverse transcription-PCR. Protein
      expression was assessed by Western blotting and immunohistochemistry. Gene and
      protein expression of VEGF, Ang-1, and Ang-2 were increased by angiotensin II
      infusion. Valsartan and PD123319 attenuated angiotensin II-associated increases
      in VEGF gene and protein expression. Ang-1 and Ang-2 gene but not protein
      expression were reduced by both treatments. These changes occurred in the context
      of attenuation of angiotensin II-induced glomerular cell proliferation by both
      valsartan and PD123319. In situ hybridization and immunohistochemical studies
      localized VEGF, Ang-1, and Ang-2 expression to the epithelial cells of the
      glomerulus, and VEGF-R2 and Tie-2 receptors to the endothelial cells of the
      kidney. These findings extend the increasing evidence that the AT(2) receptor, in
      addition to the AT(1) receptor subtype, plays an important role in mediating the
      proliferative actions of angiotensin II in the kidney.

PMID- 14638906
TI  - Intracellular mechanisms of cyclosporin A-induced tubular cell apoptosis.
AB  - Tubular cell apoptosis contributes to the pathogenesis of renal injury. However,
      the intracellular pathways that are active in tubular epithelium are poorly
      understood. The lethal pathways activated by cyclosporin A (CsA), a nephrotoxin
      that induces caspase-dependent apoptosis in tubular epithelium, were explored.
      Fas expression, caspase activation, and mitochondrial injury were assessed by
      Western blot, flow cytometry, and microscopy in cultured murine tubular
      epithelial cells exposed to CsA. The influence of FasL antagonists, Bax antisense
      oligodeoxynucleotides, and caspase inhibitors on cell survival was explored.
      Tubular cells constitutively express FasL. CsA increased the expression of Fas.
      However, Fas had no role in CsA-induced apoptosis, as CsA did not sensitize to
      FasL-induced apoptosis, caspase-8 activity was not increased, and neither
      blocking anti-FasL antibodies nor caspase-8 inhibition prevented CsA-induced
      apoptosis. Apoptosis induced by CsA is associated with the translocation of Bax
      to the mitochondria and Bax antisense oligodeoxynucleotides protected from CsA
      induced apoptosis. CsA promoted a caspase-independent release of cytochrome c and
      Smac/Diablo from mitochondria. CsA also led to a caspase-dependent loss of
      mitochondrial membrane potential. Caspase-2, caspase-3, and caspase-9 were
      activated, and specific caspase inhibitor prevented apoptosis and increased long
      term survival. Evidence for endoplasmic reticulum stress, such as induction of
      GADD153, was also uncovered. However, endoplasmic reticulum-specific caspase-12
      was not activated. CsA induces changes in several apoptotic pathways. However,
      the main lethal apoptotic pathway in CsA-exposed tubular epithelial cells
      involves mitochondrial injury.

PMID- 14638907
TI  - A major gene locus links early onset albuminuria with renal interstitial fibrosis
      in the MWF rat with polygenetic albuminuria.
AB  - The development of renal interstitial fibrosis (RIF) represents an important step
      in the progression of chronic proteinuric nephropathies. The Munich Wistar
      Fromter (MWF) rat represents a valuable model to study the progression in
      proteinuric renal disease. MWF animals demonstrate a significant increase of
      urinary albumin excretion (UAE) and RIF compared with the spontaneously
      hypertensive rat (SHR) with low UAE. The aim of this study was to analyze the
      genetic basis and the relation between UAE and RIF by genetic linkage and
      quantitative trait loci (QTL) mapping analysis. The authors generated a backcross
      population between MWF and SHR including 215 male animals. UAE was determined in
      young backcross animals at 8 wk, and at 14 and 24 wk of age, respectively. RIF
      was evaluated by Sirius red staining of kidney sections and quantified by
      computer-assisted image analysis at 24 wk. Total genome scan analysis identified
      in total eight QTL linked to UAE and a major locus on chromosome 6. At this
      locus, homozygosity for the MWF allele exhibited a strong effect on UAE levels
      (threefold elevation) and displayed significant linkage already at 8 wk
      (logarithm of odds [LOD] = 4.3) with increasing significance at 14 and 24 wk (LOD
      = 7.8 and 10.1, respectively). In addition, this was the only QTL that was linked
      to the amount of RIF (P = 0.0009, LOD = 2.4). These data establish a genetic link
      between early onset albuminuria and progression of RIF at the QTL on RNO6. This
      study demonstrates the power of genetic linkage analysis for the dissection of
      physiologic pathways involved in renal disease progression.

PMID- 14638908
TI  - Leukemia inhibitory factor is involved in tubular regeneration after experimental
      acute renal failure.
AB  - Leukemia inhibitory factor (LIF) is known to play a crucial role in the
      conversion of mesenchyme into epithelium during nephrogenesis. This study was
      carried out to test the hypothesis that LIF and LIF receptor (LIFR) are involved
      in the renal epithelial regeneration after acute renal failure. First, the
      authors investigated the spatiotemporal expression of LIF and LIFR in fetal and
      adult rat kidney. In developing kidney, LIF was expressed in the ureteric buds
      and LIFR was located in nephrogenic mesenchyme and the ureteric buds; in adult
      kidney, LIF and LIFR expression was confined to the collecting ducts. Next, the
      authors examined the expression of LIF and LIFR during the recovery phase after
      ischemia-reperfusion injury. Real-time PCR analysis revealed that LIF mRNA
      expression was significantly increased from day 1 to day 7 after reperfusion and
      that LIFR mRNA was upregulated from day 4 to day 14. Histologic analysis
      demonstrated that the increased expression of LIF mRNA and protein was most
      marked in the outer medulla, especially in the S3 segment of the proximal
      tubules. To elucidate the mitogenic role of LIF in the regeneration process,
      cultured rat renal epithelial (NRK 52E) cells were subjected to ATP depletion (an
      in vitro model of acute renal failure), and LIF expression was found to be
      enhanced during recovery after ATP depletion. Blockade of endogenous LIF with a
      neutralizing antibody significantly reduced the cell number and DNA synthesis
      during the recovery period. These results suggest that LIF participates in the
      regeneration process after tubular injury.

PMID- 14638909
TI  - Decreases in renal functional reserve and proximal tubular fluid output in
      conscious oophorectomized rats: normalization with sex hormone substitution.
AB  - Age-dependent glomerulosclerosis with reduced GFR develops earlier among men than
      among women. Therefore, whether female sex hormones could prevent the age
      dependent decrease in GFR was investigated. The kidney function in
      oophorectomized rats treated with placebo (OOX group), estrogen (OOX+E(2) group),
      or estrogen plus progesterone (OOX+E(2)+P group) for 5 mo and in sham-operated
      rats (sham group) was examined. The rats were 13 mo of age at the time of the
      investigation. They were conscious and chronically instrumented. The results
      demonstrated that estrogen, alone or in combination with progesterone, was
      without effect on the baseline GFR and effective renal plasma flow but prevented
      severe decreases in the renal functional reserve and fractional proximal tubular
      fluid output (lithium clearance technique, fractional lithium excretion), which
      were observed in the OOX group. The renal functional reserve (estimated by
      stimulation with glycine) was -223 +/- 151, 483 +/- 129, 675 +/- 76, and 208 +/-
      140 micro l/min in the OOX, OOX+E(2), OOX+E(2)+P, and sham groups, respectively.
      Fractional lithium excretion was 12.4 +/- 3.1, 26.8 +/- 2.0, 31.8 +/- 2.5, and
      23.6 +/- 3.3% in the OOX, OOX+E(2), OOX+E(2)+P, and sham groups, respectively. In
      conclusion, oophorectomy at the age of 8 mo did not produce a decrease in
      baseline GFR in female rats within a period of 5 mo. However, oophorectomy led to
      severe decreases in the renal functional reserve and fractional proximal tubular
      fluid output. Both effects were prevented with administration of estrogen. Sham
      operated rats demonstrated values for renal functional reserve and fractional
      lithium excretion that were between those observed for the OOX group and the
      groups treated with sex hormones.

PMID- 14638910
TI  - IFN-inducible protein-10 has a differential role in podocyte during Thy 1.1
      glomerulonephritis.
AB  - IFN-inducible protein-10 (IP-10/CXCL10) is a potent chemoattractant for activated
      T lymphocytes and was recently reported to have several additional biologic
      activities. In this study, the expression and the function in normal glomeruli
      and in Thy1.1 glomerulonephritis (GN) were investigated. The expression of IP-10
      was detected in normal rat glomeruli mainly in the podocyte. The expression of IP
      10 was also detected on the cultured podocyte. The IP-10 expression was elevated
      at the early phase of Thy1.1 GN. The double staining immunofluorescence study
      clearly demonstrated that the elevated expression of IP-10 was mostly detected in
      the podocyte and very partly in mesangial area. A receptor for IP-10, CXCR3,
      showed similar expression patterns to that of IP-10. Expressions of neither of IP
      10 nor of CXCR3 were detected on the inflammatory cells. For elucidating the role
      of IP-10, the blocking study was carried out with monoclonal anti-IP-10 antibody.
      The monoclonal anti-IP-10 antibody treatment decreased the expression of IP-10
      and podocyte-associated proteins such as nephrin and podocin that are reported to
      be essential for maintaining the podocyte function (IP-10, 53.0% to control;
      nephrin, 43.5%; podocin, 60.4%). The findings indicated that the anti-IP-10
      treatment disturbed the podocyte function. The anti-IP-10 treatment given to the
      rats with Thy1.1 nephritis exacerbated proteinuria, mesangiolysis, and matrix
      expansion. Collectively, the findings indicated that IP-10 plays a role in
      maintaining the podocyte function. Also, the findings suggested that anti-IP-10
      treatment exacerbated the glomerular alterations in Thy1.1 GN by disturbing the
      podocyte function.

PMID- 14638911
TI  - Polymeric IgA1 from patients with IgA nephropathy upregulates transforming growth
      factor-beta synthesis and signal transduction in human mesangial cells via the
      renin-angiotensin system.
AB  - The effects of polymeric IgA1 (pIgA1) and monomeric IgA1 (mIgA1) from patients
      with IgA nephropathy (IgAN) on the renin-angiotensin system (RAS) and TGF-beta
      synthesis were examined in cultured human mesangial cells (HMC). Both pIgA1 and
      mIgA1 induced renin gene expression in HMC, in a dose-dependent manner. Similar
      findings were observed for TGF-beta gene and protein expression. The values
      measured in HMC incubated with pIgA1 were significantly higher than those in HMC
      incubated with equivalent amounts of mIgA1. When similar experiments were
      performed with the addition of either captopril or losartan, there was a
      significant increase in the renin gene expression by HMC, whereas the synthesis
      of TGF-beta was markedly reduced. The TGF-beta signal transduction pathways in
      HMC were studied by measuring the receptor-regulated Smad proteins (Smad 2 and 3)
      and common-partner Smad proteins (Smad 4). pIgA1 from patients with IgAN
      upregulated Smad activity in HMC, and the activity observed in HMC that had been
      preincubated with pIgA1 was readily suppressed with optimal concentrations of
      captopril or losartan. The effects of pIgA1 on the RAS were further examined in
      HMC incubated with IgA isolated from 30 patients with IgAN, 30 healthy subjects,
      and disease control subjects with other diseases. pIgA1 induction of angiotensin
      II or TGF-beta synthesis in HMC was significantly greater with preparations from
      patients with IgAN, compared with healthy or disease control subjects. The
      findings support a pathogenetic role of pIgA1 in IgAN through upregulation of the
      RAS and TGF-beta, leading to chronic renal failure with renal fibrosis.

PMID- 14638912
TI  - Identification of renal progenitor-like tubular cells that participate in the
      regeneration processes of the kidney.
AB  - The present study was conducted to explore renal progenitor-like cells that are
      actively engaged in tubular regeneration after injury. For addressing this issue,
      the existence of label-retaining cells (LRC; slow-cycling cells) in normal rat
      kidneys by in vivo bromodeoxyuridine (BrdU) labeling was examined. LRC were
      scattering among renal epithelial tubular cells of normal rat kidneys. During the
      recovery after renal ischemia, LRC underwent cell division and most of them
      became positive for proliferating cell nuclear antigen. In contrast,
      proliferating cell nuclear antigen-positive but BrdU-negative tubular cells were
      rarely observed, suggesting that cells proliferating during tubular regeneration
      are essentially derived from LRC. At an early phase of tubular regeneration,
      descendants of LRC expressed a mesenchymal marker, vimentin, and eventually
      became positive for an epithelial marker, E-cadherin, after multiple cell
      divisions. These findings suggested that LRC function as a source of regenerating
      cells to replace injured cells. Collectively, it was concluded that LRC are renal
      progenitor-like tubular cells that provide regenerating cells, which actively
      proliferate and eventually differentiate into epithelial cell, during tubular
      regeneration. It may be possible to regenerate renal tubules in vivo through the
      activation of LRC.

PMID- 14638913
TI  - Importance of functional EGF receptors in recovery from acute nephrotoxic injury.
AB  - Previous studies have demonstrated increased renal expression of EGF receptor
      (EGFR) and EGFR ligands in response to acute toxic or ischemic renal tubular
      injury and have indicated that exogenous administration of EGF accelerates
      recovery from such injury. However, no studies to date have proved definitively
      an essential role for EGFR-mediated responses in regeneration after tubule
      injury. To this end, waved-2 (wa-2) mice, which contain a point mutation in EGFR
      that reduces receptor tyrosine kinase activity by >90%, were studied. These mice
      have a mild phenotype (wavy coat, curly whiskers, and runted stature) and
      normally developed kidneys. Acute nephrotoxic injury was induced in wa-2 and wild
      type mice with HgCl(2). One day after HgCl(2) injection, functional renal
      compromise was comparable in wild-type and wa-2 mice. However, the rates of
      recovery of serum blood urea nitrogen and creatinine levels were markedly slower
      in wa-2 mice. Histologic evidence of tubular injury also was more severe and
      persisted longer in wa-2 mice. Furthermore, their kidneys demonstrated reduced
      levels of DNA synthesis and increased TdT-mediated dUTP nick-end labeling
      staining. These studies indicate that functional EGFR activity is an essential
      component of the kidney's ability to recover from acute injury and that EGFR may
      regulate genes involved in growth, repair, and cell survival in the kidney.

PMID- 14638914
TI  - Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44
      expressing injured/regenerating tubular epithelial cells in rat kidneys.
AB  - Retention of crystals in the kidney is an essential early step in renal stone
      formation. Studies with renal tubular cells in culture indicate that hyaluronan
      (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an
      important role in calcium oxalate (CaOx) crystal binding during wound healing.
      This concept was investigated in vivo by treating rats for 1, 4, and 8 d with
      ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular
      cell damage and CaOx crystalluria. Tubular injury was morphologically scored on
      periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by
      immunohistochemical staining for proliferating cell nuclear antigen. CaOx
      crystals were visualized in periodic acid-Schiff-stained sections by polarized
      light microscopy, and renal calcium deposits were quantified with von Kossa
      staining. HA was visualized with HA-binding protein and OPN and CD44
      immunohistochemically with specific antibodies and quantified with an image
      analyzer system. Already after 1 d of treatment, both concentrations of ethylene
      glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was
      neither tubular injury nor crystal retention in the kidney, and expression of HA,
      OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene
      glycol, however, intratubular crystals were found adhered to injured/regenerating
      (proliferating cell nuclear antigen positive) tubular epithelial cells,
      expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the
      expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to
      play a role in retention of crystals in the rat kidney.

PMID- 14638915
TI  - Downregulation of Smad transcriptional corepressors SnoN and Ski in the fibrotic
      kidney: an amplification mechanism for TGF-beta1 signaling.
AB  - TGF-beta1 is a profibrotic cytokine that plays a central role in the onset and
      progression of chronic renal diseases. The activity of TGF-beta1 is tightly
      controlled by multiple mechanisms, in which antagonizing Smad-mediated gene
      transcription by co-repressors is an important regulatory component. This study
      examined the expression of Smad transcriptional co-repressors in the fibrotic
      kidney and investigated their potential functions in controlling TGF-beta1
      response. Western blot analysis demonstrated that the protein levels of Smad
      transcriptional co-repressors SnoN and Ski were progressively reduced in a time
      dependent manner in the fibrotic kidney induced by unilateral ureteral
      obstruction in mice, whereas renal Smad abundance was relatively unaltered.
      Consistently, SnoN and Ski staining was diminished in the nuclei of renal tubular
      epithelium and interstitium after obstructive injury. In vitro, knockdown of SnoN
      expression by RNA interference in tubular epithelial cells dramatically
      sensitized their responsiveness to TGF-beta1 stimulation. Conversely, ectopic
      expression of exogenous SnoN or Ski after transfection conferred tubular
      epithelial cell resistance to TGF-beta1-induced epithelial to myofibroblast
      transition. Both SnoN and Ski could block Smad-mediated activation of TGF-beta1
      responsive promoter and exhibited additive effect in abrogating the profibrotic
      actions of TGF-beta1. These results indicate that as a result of loss of Smad
      transcriptional co-repressors, the profibrotic TGF-beta1 signaling in diseased
      kidney is markedly amplified in a magnitude much greater than previously thought.
      Therefore, new strategy aimed to increase Smad transcriptional co-repressors
      expression may be effective in antagonizing TGF-beta1 signaling and thereby
      blocking the progression of chronic renal fibrosis.

PMID- 14638916
TI  - Role of 12-lipoxygenase in the stimulation of p38 mitogen-activated protein
      kinase and collagen alpha5(IV) in experimental diabetic nephropathy and in
      glucose-stimulated podocytes.
AB  - The 12-lipoxygenase (12-LO) pathway of arachidonic acid metabolism is implicated
      in extracellular matrix (ECM) synthesis, but its role in podocytes has not been
      studied. This study tested whether 12-LO induction by diabetes or by high glucose
      (HG) in cultured podocytes alters glomerular basement membrane by activating
      signal transduction pathways culminating in ECM synthesis. Sprague-Dawley rats
      received an injection of diluent (control [C]) or streptozotocin 65 mg/kg (DM)
      and were killed at 1 or 4 mo. Glomerular 12-LO mRNA and protein levels were
      higher in DM than in C glomeruli at 1 and 4 mo, and 12-LO localized predominantly
      in podocytes. Glomerular p38 mRNA and protein were higher in DM at months 1 and
      4, but phospho-p38 mitogen-activated protein (MAPK) was increased only at month
      1. Glomerular collagen alpha5(IV)/glutaraldehyde-3-phosphate dehydrogenase
      (GAPDH) mRNA ratio was increased in DM at month 1 but not at month 4, whereas
      collagen alpha5(IV) protein was higher at both 1 and 4 mo. Mouse podocytes were
      cultured in media with 25 mM glucose (HG) with or without the 12-LO inhibitor
      cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) or with 5.5 mM glucose + 19.5 mM
      mannitol (low glucose [LG+M]) for 10 d at 37 degrees C. 12-LO mRNA and protein
      levels were higher in HG than in LG+M as was the p38 MAPK/GAPDH mRNA ratio.
      Phospho-p38 MAPK protein but not total p38 MAPK was higher in HG compared with
      LG+M. Collagen alpha5(IV)/GAPDH mRNA ratio and protein were higher in HG than in
      LG+M. 12-LO inhibition by CDC decreased HG-induced phospho-p38 MAPK and the
      phospho-p38/total p38 MAPK ratio, collagen alpha5(IV)/GAPDH mRNA ratio, and
      collagen alpha5(IV) protein expression. In summary, diabetes in vivo and exposure
      of podocytes to HG in vitro stimulated 12-LO, p38 MAPK, and collagen alpha5(IV)
      mRNA and (activated) protein. 12-LO inhibition by CDC diminished the expression
      of podocyte phospho-p38 MAPK and collagen alpha5(IV) mRNA and protein. These
      findings implicate 12-LO and the p38 MAPK signaling pathway in the mediation of
      ECM synthesis by podocytes in diabetes.

PMID- 14638917
TI  - Cyclosporin A administration during pregnancy induces a permanent nephron deficit
      in young rabbits.
AB  - Cyclosporin A (CsA) is an immunosuppressive agent used to prevent graft rejection
      and to treat autoimmune disorders. Successful pregnancies can be achieved among
      CsA-treated women, although it is known that CsA is nephrotoxic and crosses the
      human placenta. The aim of this study was to evaluate the harmlessness of CsA
      toward the embryonic kidney. Twenty-one pregnant rabbits were divided into four
      groups. Groups of six and four female animals were subjected to daily injections
      of 10 mg/kg per d CsA (administered subcutaneously) for 5 d, from day 14 to day
      18 of gestation or from day 20 to day 24 of gestation, respectively. In the third
      group, five female animals received the CsA diluent (Cremophor) from day 14 to
      day 18 of gestation. The fourth group consisted of six untreated female animals.
      Pregnancy outcomes among CsA-treated does demonstrated a reduced number of living
      pups, which were also growth-retarded, with exposure to CsA from day 20 to day 24
      of gestation. However, pups exposed to CsA from day 14 to day 18 of gestation
      exhibited normal fetal growth, and blood concentrations of CsA matched human
      data. Examinations of kidneys at birth demonstrated vacuolation of proximal and
      collecting tubules and ureteric bud ends. Increased glomerular volumes and
      decreased nephron densities suggested nephron mass reduction, which was
      quantitatively evaluated in 1-mo-old animals. The nephron numbers were reduced by
      25 and 33% in day 14 to 18 CsA-treated and day 20 to 24 CsA-treated animals,
      respectively, which displayed compensatory adaptation of the existing nephrons.
      However, foci of segmental glomerular sclerosis were already present, which would
      possibly jeopardize renal function later in life.

PMID- 14638918
TI  - Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK
      virus-specific cytotoxic T-cell lines in seropositive healthy individuals and
      renal transplant recipients.
AB  - Polyoma BK virus (BKV)-associated interstitial nephritis has emerged as a
      relevant complication of immunocompromise after kidney transplantation, leading
      to reduced survival of the renal allograft. The limitations of current antiviral
      treatment and the high probability of rejection in kidney graft recipients when
      control of viral replication is attempted by reduction of immunosuppression
      warrant further efforts to develop alternative therapeutic tools. Cellular
      immunotherapy has proved to be a successful approach for prevention and/or
      treatment of other viral complications in the immunocompromised host. For
      assessing the feasibility of translating this strategy to the prevention of BKV
      associated disease, a procedure for ex vivo reactivation of BKV-specific
      cytotoxic T cells (CTL) was developed from BKV-seropositive healthy donors and
      allograft recipients through stimulation with dendritic cells pulsed with
      inactivated BKV. The CTL lines thus obtained showed BKV specificity, as an
      efficient lysis of BKV-infected targets was accompanied by little or no
      reactivity against mock-infected autologous or allogeneic targets. In vitro
      killing of allogeneic BKV-infected targets, likely as a result of populations of
      TCRgammadelta+/CD3+ displaying MHC class I unrestricted cytotoxicity, was also
      displayed. Application of this culture system may allow a preemptive therapy
      approach to BKV-related complications in transplant recipients, based on CTL
      treatment guided by BKV DNA levels.

PMID- 14638919
TI  - Mice that lack endothelial nitric oxide synthase are protected against functional
      and structural modifications induced by acute peritonitis.
AB  - Pharmacologic studies suggest that the release of nitric oxide (NO) by
      endothelial NO synthase (eNOS) contributes to functional alterations of the
      peritoneal membrane (PM) induced by acute peritonitis. In this study, peritoneal
      permeability parameters in a mouse model of peritoneal dialysis were
      characterized, and the effects of eNOS deletion on the PM structure and
      permeability at baseline and after catheter-induced bacterial peritonitis were
      examined. Exposure of C57BL/6 mice to standard dialysate yielded a transport of
      urea and glucose, a sodium sieving, and a net ultrafiltration that were
      remarkably similar to the values obtained in rats. In comparison with controls,
      mice with catheter-induced peritonitis were characterized by structural changes
      in the PM (mononuclear cells infiltrate, vascular proliferation), upregulation of
      endothelial and inducible NOS, increased permeability for urea and glucose,
      decreased ultrafiltration, and increased protein loss in the dialysate.
      Comparison of eNOS wild-type and knockout mice revealed that the permeability
      modifications and structural changes induced by acute peritonitis were
      significantly reversed in eNOS knockout mice, resulting in a net increase in
      ultrafiltration. In contrast, the deletion of eNOS in mouse peritoneum was not
      reflected by permeability modifications or structural changes at baseline. These
      results are the first to take advantage of a knockout mouse model to demonstrate
      directly the crucial importance of eNOS in the permeability and structural
      modifications caused by acute peritonitis. The characterization of this mouse
      model suggests that genetically modified mice represent useful tools to
      investigate the molecular bases of the peritoneal changes during peritoneal
      dialysis.

PMID- 14638920
TI  - Management of glomerular proteinuria: a commentary.
AB  - It is widely accepted that proteinuria reduction is an appropriate therapeutic
      goal in chronic proteinuric kidney disease. Based on large randomized controlled
      clinical trials (RCT), ACE inhibitor (ACEI) and angiotensin receptor blocker
      (ARB) therapy have emerged as the most important antiproteinuric and renal
      protective interventions. However, there are numerous other interventions that
      have been shown to be antiproteinuric and, therefore, likely to be
      renoprotective. Unfortunately testing each of these antiproteinuric therapies in
      RCT is not feasible. The nephrologist has two choices: restrict antiproteinuric
      therapies to those shown to be effective in RCT or expand the use of
      antiproteinuric therapies to include those that, although unproven, are plausibly
      effective and prudent to use. The goal of this work is to provide the
      documentation needed for the nephrologist to choose between these strategies.
      This work describes 25 separate interventions that are either antiproteinuric or
      may block injurious mechanisms of proteinuria. Each intervention is assigned a
      level of recommendation (Level 1 is the highest; Level 3 is the lowest) according
      to the strength of the evidence supporting its antiproteinuric and renoprotective
      efficacy. Pathophysiologic mechanisms possibly involved are also discussed. The
      number of interventions at each level of recommendation are: Level 1, n = 7;
      Level 2, n = 9; Level 3, n = 9. Our experience indicates that we can achieve in
      most patients the majority of Level 1 and many of the Level 2 and 3
      recommendations. We suggest that, until better information becomes available, a
      broad-based, multiple-risk factor intervention to reduce proteinuria can be
      justified in those with progressive nephropathies. This work is intended
      primarily for clinical nephrologists; therefore, each antiproteinuria
      intervention is described in practical detail.

PMID- 14638921
TI  - Association between renal insufficiency and inducible ischemia in patients with
      coronary artery disease: the heart and soul study.
AB  - Chronic renal insufficiency (CRI) is a predictor of stroke, cardiovascular, and
      all-cause mortality, but the mechanisms responsible for these associations are
      unclear. Whether CRI was associated with severity of coronary artery disease
      (CAD) as measured by exercise stress echocardiography among outpatients with
      stable CAD was evaluated. This study is a cross-sectional analysis of the Heart
      and Soul study, a prospective cohort of patients with known CAD. Renal function
      was assessed by 24-h urine collection, and CRI was defined as measured creatinine
      clearance < or =60 ml/min. Exercise stress echocardiography was used to identify
      inducible ischemia, defined as any wall motion abnormality seen at stress but not
      at rest. Logistic regression was used to evaluate the association of CRI with
      exercise-induced ischemia after adjustment for cardiovascular risk factors.
      Participants with CRI composed 97 (23%) of the 431 participants and were
      characterized by older age, worse CAD, lower ejection fraction, greater left
      ventricular mass and higher C-reactive protein values. The prevalence of exercise
      induced ischemia was also substantially greater in the participants with CRI (42%
      versus 23%; odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4 to 3.8; P <
      0.001). This association was minimally changed by adjustment for traditional
      cardiovascular risk factors and coronary disease history (OR, 2.0; 95% CI, 1.3 to
      3.3; P < 0.01) and remained strong even after adjustment for C-reactive protein
      (OR, 2.3; 95% CI, 1.0 to 5.1; P = 0.04). CRI is strongly associated with exercise
      induced ischemia in patients with CAD. The greater severity of atherosclerotic
      disease observed in patients with CRI may in part explain the association of CRI
      with increased cardiovascular risk among individuals with CAD.

PMID- 14638922
TI  - Sympathetic nerve activity is inappropriately increased in chronic renal disease.
AB  - The hypothesis that in hypertensive patients with renal parenchymal disease
      sympathetic activity is "inappropriately" elevated and that this overactivity is
      a feature of renal disease and not of a reduced number of nephrons per se is
      addressed. Fifty seven patients with renal disease (various causes, no diabetes,
      all on antihypertensive medication) were studied, age range 18 to 62, creatinine
      clearance 10 to 114 ml/min per 1.73 m(2). Antihypertensives were stopped, but
      diuretics were allowed, to prevent overhydration. Matched control subjects were
      also studied. The effect of changes in fluid status was examined in seven
      patients while on and after stopping diuretics and in eight control subjects
      while on low- and high-sodium diet. Seven kidney donors were studied before and
      after unilateral nephrectomy. Sympathetic activity was quantified as muscle
      sympathetic nerve activity (MSNA) in the peroneal nerve. Mean arterial pressure,
      MSNA, and plasma renin activity were higher in patients than in control subjects,
      respectively (115 +/- 12 and 88 +/- 11 mmHg, 31 +/- 15 and 18 +/- 10 bursts/min,
      and 500 [20 to 6940] and 220 [40 to 980] fmol/L per s; P < 0.01 for all items).
      Extracellular fluid volume (bromide distribution) did not differ. Seven patients
      were studied again after stopping diuretics. MSNA decreased from 34 +/- 18 to 19
      +/- 18 bursts/min (P < 0.01). Eight healthy subjects were studied during low- and
      high-sodium diet. MSNA was 26 +/- 12 and 13 +/- 7 bursts/min (P < 0.01). The
      curves relating extracellular fluid volume to MSNA were parallel in the two
      groups but shifted to a higher level of MSNA in the patients. In the kidney
      donors, creatinine clearance reduced by 25%, but MSNA was identical before and
      after donation. It is concluded that in hypertensive patients with renal
      parenchymal disease, sympathetic activity is inappropriately high for the volume
      status and that reduction of nephron number in itself does not influence
      sympathetic activity.

PMID- 14638923
TI  - Beta1-adrenergic blockade augments pulsatile PTH secretion in humans.
AB  - Pulsatile peptide hormone secretion provides efficient control of specific end
      organ functions. To test the hypothesis that sympathetic neuronal activity drives
      synchronous pulsatile PTH release from the parathyroid glands, we investigated
      the acute effects of beta1-adrenergic receptor blockade on PTH secretion patterns
      in a single-blinded study in nine healthy adults. Plasma PTH levels were
      determined at 1-min intervals. After a 75-min baseline period, seven subjects
      received a continuous intravenous infusion of the short-acting beta1-adrenergic
      receptor blocker esmolol for 105 min. After a 30-min washout period, esmolol was
      infused for another 30 min. Two additional subjects were randomized to receive
      solvent infusions. PTH secretion characteristics were analyzed by multiparameter
      deconvolution analysis, and the orderliness of plasma PTH fluctuations by
      Approximate Entropy statistics. BP slightly decreased during esmolol infusion,
      whereas heart rate, ionized calcium, phosphate, magnesium, and plasma and urine
      catecholamines remained unchanged. Esmolol increased mean plasma PTH by 33 +/- 8%
      (P < 0.01), due to a preferential increase in the pulsatile PTH secretion
      component (+129 +/- 44%, P < 0.02). The increased pulsatile PTH secretion was
      mediated by an augmented PTH burst mass (+117 +/- 42%, P < 0.01), whereas burst
      frequency remained unchanged. The regularity of PTH fluctuations was not affected
      by the beta-adrenergic blockade. The effects were reproducible during the second
      esmolol infusion. The authors conclude that the sympathetic nervous system has a
      modulating effect on pulsatile PTH secretion. Selective beta-1 adrenergic
      blockade acutely increases plasma PTH by augmenting the mass of hormone secreted
      per burst, but it does not alter the rhythmicity of pulsatile PTH release.

PMID- 14638924
TI  - Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO
      study.
AB  - Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not
      significantly affect the primary outcome of the all-cause mortality (ACM) rate or
      the main secondary composite outcomes, including the rates of first cardiac
      hospitalization or ACM, first infectious hospitalization or ACM, first 15%
      decrease in serum albumin levels or ACM, or all non-vascular access-related
      hospitalizations. The high-flux intervention, however, seemed to be associated
      with reduced risks of specific cardiac-related events. The relative risks (RR)
      for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence
      interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00)
      for the composite of first cardiac hospitalization or cardiac death. Also, the
      effect of high-flux dialysis on ACM seemed to vary, depending on the duration of
      prior dialysis. This report presents secondary analyses to further explore the
      relationship between the flux intervention and the duration of dialysis with
      respect to various outcomes. The patients were stratified into a short-duration
      group and a long-duration group, on the basis of the mean duration of dialysis of
      3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7
      yr, randomization to high-flux dialysis was associated with lower risks of ACM
      (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level
      decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths
      (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No
      significant differences were observed in outcomes related to infection for either
      duration subgroup, however, and the trends for beneficial effects of high-flux
      dialysis on ACM rates were considerably weakened when the years of dialysis
      during the follow-up phase were combined with the prestudy years of dialysis in
      the analysis. For the subgroup of patients with <3.7 yr of dialysis before the
      study, assignment to high-flux dialysis had no significant effect on any of the
      examined clinical outcomes. These data suggest that high-flux dialysis might have
      a beneficial effect on cardiac outcomes. Because these results are derived from
      multiple statistical comparisons, however, they must be interpreted with caution.
      The subgroup results that demonstrate that patients with different durations of
      dialysis are affected differently by high-flux dialysis are interesting and
      require further study for confirmation.

PMID- 14638925
TI  - Best threshold for diagnosis of stenosis or thrombosis within six months of
      access flow measurement in arteriovenous fistulae.
AB  - Canadian clinical practice guidelines recommend performing angiography when
      access blood flow (Qa) is <500 ml/min in native vessel arteriovenous fistulae
      (AVF), but data on the value of Qa that best predicts stenosis are sparse.
      Because correction of stenosis in AVF improves patency rates, this issue seems
      worthy of investigation. Receiver-operating characteristic curves were
      constructed to examine the relationship between different threshold values of Qa
      and stenosis in 340 patients with AVF. Stenosis was defined by the composite
      outcome of access failure or angiographic stenosis occurring within 6 mo of the
      first Qa measurement. The Qa value was then classified as true negative, true
      positive, false negative, or false positive for stenosis. An additional analysis
      was performed in which Qa was corrected for systolic BP before assigning it to
      one of the four diagnostic categories. The area under the curve for the composite
      definition of stenosis was 0.86. Graphically, Qa thresholds of <500 and <600
      ml/min had similar efficacy for detecting stenosis or access failure within 6 mo,
      and both seemed superior to <400 ml/min. However, the frequency of the composite
      definition of stenosis among AVF with Qa between 500 and 600 ml/min was only 6
      (25%) of 24, as compared with 58 (76%) of 76 when Qa was <500 ml/min. This
      suggests that most lesions that would be found using a threshold of <600 ml/min
      occurred in AVF with Qa <500 ml/min and that the small gain in sensitivity
      associated with the <600-ml/min threshold would be outweighed by the reduced
      specificity compared with <500 ml/min. Correcting Qa for BP did not improve
      diagnostic performance or change these results, which were consistent in several
      sensitivity analyses. Qa measurements seemed to predict stenosis or incipient
      access failure equally well in groups defined by diabetic status, gender, and AVF
      location. In conclusion, it was found that Qa <500 ml/min seems to be the most
      appropriate threshold for performing angiography in patients with native vessel
      AVF. It is recommended that clinicians arrange angiography when Qa is <500 ml/min
      in AVF.

PMID- 14638926
TI  - Association of comorbid conditions and mortality in hemodialysis patients in
      Europe, Japan, and the United States: the Dialysis Outcomes and Practice Patterns
      Study (DOPPS).
AB  - Mortality rates among hemodialysis patients vary greatly across regions.
      Representative databases containing extensive profiles of patient characteristics
      and outcomes are lacking. The Dialysis Outcomes and Practice Patterns Study
      (DOPPS) is a prospective, observational study of representative samples of
      hemodialysis patients in France, Germany, Italy, Japan, Spain, the United
      Kingdom, and the United States (US) that captures extensive data relating to
      patient characteristics, prescriptions, laboratory values, practice patterns, and
      outcomes. This report describes the case-mix features and mortality among 16,720
      patients followed up to 5 yr. The crude 1-yr mortality rates were 6.6% in Japan,
      15.6% in Europe, and 21.7% in the US. After adjusting for age, gender, race, and
      25 comorbid conditions, the relative risk (RR) of mortality was 2.84 (P < 0.0001)
      for Europe compared with Japan (reference group) and was 3.78 (P < 0.0001) for
      the US compared with Japan. The adjusted RR of mortality for the US versus Europe
      was 1.33 (P < 0.0001). For most comorbid diseases, prevalence was highest in the
      US, where the mean age (60.5 +/- 15.5 yr) was also highest. Older age and
      comorbidities were associated with increased risk of death (except for
      hypertension, which carried a multivariate RR of mortality of 0.74 [P < 0.0001]).
      Variability in demographic and comorbid conditions (as identified by dialysis
      facilities) explains only part of the differences in mortality between dialysis
      centers, both for comparisons made across continents and within the US.
      Adjustments for the observed variability will allow study of association between
      practice patterns and outcomes.

PMID- 14638927
TI  - Differential expression of heme oxygenase-1 and vascular endothelial growth
      factor in cadaveric and living donor kidneys after ischemia-reperfusion.
AB  - The extent of graft damage after ischemia-reperfusion reflects the balance
      between deleterious events and protective factors. Heme oxygenase-1 (HO-1) and
      vascular endothelial growth factor (VEGF) may contribute to cytoprotection by
      their anti-inflammatory and antiapoptotic properties. For investigating whether
      HO-1 and VEGF play a role in the adaptive response to ischemia-reperfusion injury
      after renal transplantation, kidney biopsies were analyzed from living (n = 45)
      and cadaveric (n = 16) donors, obtained at three time points: at the end of cold
      storage T(-1), after warm ischemia T(0), and after reperfusion T(+1). The mRNA
      expression levels of HO-1, VEGF(165), Bcl-2, Bax, and hypoxia inducible factor
      1alpha were quantified by real-time reverse transcriptase-PCR, and the HO-1 and
      VEGF proteins were analyzed by immunohistochemistry. Cadaveric donor kidneys
      presented higher mRNA expression levels of hypoxia inducible factor-1alpha. In
      contrast, mRNA expression levels of HO-1, VEGF(165), and Bcl-2 were significantly
      lower in kidneys from cadaveric donors. Overall, a significant correlation was
      observed between mRNA expression of Bcl-2 and VEGF(165), between Bcl-2 and HO-1,
      and between HO-1 and VEGF(165). Moreover, protein expression of HO-1 and VEGF was
      detected in the same anatomical kidney compartments (glomerulus, arteries, and
      distal tubules). Renal function at the first week posttransplantation (analyzed
      by serum creatinine levels) showed a significant correlation with both HO-1 and
      VEGF mRNA expression, reinforcing the protective role of both genes in the early
      events of transplantation. It is concluded that the lower expression of HO-1,
      VEGF(165), and Bcl-2 in cadaveric donor kidneys can reflect a defective
      adaptation against ischemia-reperfusion injury that may affect their function in
      the short term.

PMID- 14638928
TI  - Edema in the nephrotic syndrome: new aspect of an old enigma.

PMID- 14638929
TI  - Searching for stem/progenitor cells in the adult mouse kidney.

PMID- 14638931
TI  - Interactions between electron and proton currents in excised patches from human
      eosinophils.
AB  - The NADPH-oxidase is a plasma membrane enzyme complex that enables phagocytes to
      generate superoxide in order to kill invading pathogens, a critical step in the
      host defense against infections. The oxidase transfers electrons from cytosolic
      NADPH to extracellular oxygen, a process that requires concomitant H+ extrusion
      through depolarization-activated H+ channels. Whether H+ fluxes are mediated by
      the oxidase itself is controversial, but there is a general agreement that the
      oxidase and H+ channel are intimately connected. Oxidase activation evokes
      profound changes in whole-cell H+ current (IH), causing an approximately -40-mV
      shift in the activation threshold that leads to the appearance of inward IH. To
      further explore the relationship between the oxidase and proton channel, we
      performed voltage-clamp experiments on inside-out patches from both resting and
      phorbol-12-myristate-13-acetate (PMA)-activated human eosinophils. Proton
      currents from resting cells displayed slow voltage-dependent activation, long
      term stability, and were blocked by micromolar internal [Zn2+]. IH from PMA
      treated cells activated faster and at lower voltages, enabling sustained H+
      influx, but ran down within minutes, regaining the current properties of
      nonactivated cells. Bath application of NADPH to patches excised from PMA-treated
      cells evoked electron currents (Ie), which also ran down within minutes and were
      blocked by diphenylene iodonium (DPI). Run-down of both IH and Ie was delayed,
      and sometimes prevented, by cytosolic ATP and GTP-gamma-S. A good correlation was
      observed between the amplitude of Ie and both inward and outward IH when a stable
      driving force for e- was imposed. Combined application of NADPH and DPI reduced
      the inward IH amplitude, even in the absence of concomitant oxidase activity. The
      strict correlation between Ie and IH amplitudes and the sensitivity of IH to
      oxidase-specific agents suggest that the proton channel is either part of the
      oxidase complex or linked by a membrane-limited mediator.

PMID- 14638932
TI  - Activation of AMPA/kainate receptors but not acetylcholine receptors causes Mg2+
      influx into Retzius neurones of the leech Hirudo medicinalis.
AB  - In Retzius neurones of the medicinal leech, Hirudo medicinalis, kainate activates
      ionotropic glutamate receptors classified as AMPA/kainate receptors. Activation
      of the AMPA/kainate receptor-coupled cation channels evokes a marked
      depolarization, intracellular acidification, and increases in the intracellular
      concentrations of Na+ ([Na+]i) and Ca2+. Qualitatively similar changes are
      observed upon the application of carbachol, an activator of acetylcholine
      receptor-coupled cation channels. Using multibarrelled ion-selective
      microelectrodes it was demonstrated that kainate, but not carbachol, caused
      additional increases in the intracellular free Mg2+ concentration ([Mg2+]i).
      Experiments were designed to investigate whether this kainate-induced [Mg2+]i
      increase was due to a direct Mg2+ influx through the AMPA/kainate receptor
      coupled cation channels or a secondary effect due to the depolarization or the
      ionic changes. It was found that: (a) Similar [Mg2+]i increases were evoked by
      the application of glutamate or aspartate. (b) All kainate-induced effects were
      inhibited by the glutamatergic antagonist DNQX. (c) The magnitude of the [Mg2+]i
      increases depended on the extracellular Mg2+ concentration. (d) A reduction of
      the extracellular Ca2+ concentration increased kainate-induced [Mg2+]i increases,
      excluding possible Ca2+ interference at the Mg2+-selective microelectrode or at
      intracellular buffer sites. (e) Neither depolarizations evoked by the application
      of 30 mM K+, nor [Na+]i increases induced by the inhibition of the Na+/K+ ATPase
      caused comparable [Mg2+]i increases. (f) Inhibitors of voltage-dependent Ca2+
      channels did not affect the kainate-induced [Mg2+]i increases. Moreover, previous
      experiments had already shown that intracellular acidification evoked by the
      application of 20 mM propionate did not cause changes in [Mg2+]i. The results
      indicate that kainate-induced [Mg2+]i increases in leech Retzius neurones are due
      to an influx of extracellular Mg2+ through the AMPA/kainate receptor-coupled
      cation channel. Mg2+ may thus act as an intracellular signal to distinguish
      between glutamatergic and cholinergic activation of leech Retzius neurones.

PMID- 14638933
TI  - Pseudechetoxin binds to the pore turret of cyclic nucleotide-gated ion channels.
AB  - Peptide toxins are invaluable tools for studying the structure and physiology of
      ion channels. Pseudechetoxin (PsTx) is the first known peptide toxin that targets
      cyclic nucleotide-gated (CNG) ion channels, which play a critical role in sensory
      transduction in the visual and olfactory systems. PsTx inhibited channel currents
      at low nM concentrations when applied to the extracellular face of membrane
      patches expressing olfactory CNGA2 subunits. Surprisingly, 500 nM PsTx did not
      inhibit currents through channels formed by the CNGA3 subunit from cone
      photoreceptors. We have exploited this difference to identify the PsTx-binding
      site on the extracellular face of CNG channels. Studies using chimeric channels
      revealed that transplantation of the pore domain from CNGA2 was sufficient to
      confer high affinity PsTx binding upon a CNGA3 background. To further define the
      binding site, reciprocal mutations were made at 10 nonidentical amino acid
      residues in this region. We found that two residues in CNGA2, D316 and Y321, were
      essential for high-affinity inhibition by PsTx. Furthermore, replacement of both
      residues was required to confer high-affinity PsTx inhibition upon CNGA3. Several
      other residues, including E325, also form favorable interactions with PsTx. In
      the CNGA2-E325K mutant, PsTx affinity was reduced by approximately 5-fold to 120
      nM. An electrostatic interaction with D316 does not appear to be the primary
      determinant of PsTx affinity, as modification of the D316C mutant with a
      negatively charged methanethiosulfonate reagent did not restore high affinity
      inhibition. The residues involved in PsTx binding are found within the pore
      turret and helix, in similar positions to residues that form the receptor for
      pore-blocking toxins in voltage-gated potassium channels. Furthermore,
      biophysical properties of PsTx block, including an unfavorable interaction with
      permeant ions, also suggest that it acts as a pore blocker. In summary, PsTx
      seems to occlude the entrance to the pore by forming high-affinity contacts with
      the pore turret, which may be larger than that found in the KcsA structure.

PMID- 14638934
TI  - Effect of MyBP-C binding to actin on contractility in heart muscle.
AB  - In contrast to skeletal muscle isoforms of myosin binding protein C (MyBP-C), the
      cardiac isoform has 11 rather than 10 fibronectin or Ig modules (modules are
      identified as C0 to C10, NH2 to COOH terminus), 3 phosphorylation sites between
      modules C1 and C2, and 28 additional amino acids rich in proline in C5.
      Phosphorylation between C1 and C2 increases maximum Ca-activated force (Fmax),
      alters thick filament structure, and increases the probability of myosin heads on
      the thick filament binding to actin on the thin filament. Unphosphorylated C1C2
      fragment binds to myosin, but phosphorylation inhibits the binding. MyBP-C also
      binds to actin. Using two types of immunoprecipitation and cosedimentation, we
      show that fragments of MyBP-C containing C0 bind to actin. In low concentrations
      C0-containing fragments bind to skinned fibers when the NH2 terminus of
      endogenous MyBP-C is bound to myosin, but not when MyBP-C is bound to actin. C1C2
      fragments bind to skinned fibers when endogenous MyBP-C is bound to actin but not
      to myosin. Disruption of interactions of endogenous C0 with a high concentration
      of added C0C2 fragments produces the same effect on contractility as extraction
      of MyBP-C, namely decrease in Fmax and increase in Ca sensitivity. These results
      suggest that cardiac contractility can be regulated by shifting the binding of
      the NH2 terminus of MyBP-C between actin and myosin. This mechanism may have an
      effect on diastolic filling of the heart.

PMID- 14638935
TI  - Mechanisms underlying modulation of neuronal KCNQ2/KCNQ3 potassium channels by
      extracellular protons.
AB  - Changes in extracellular pH occur during both physiological neuronal activity and
      pathological conditions such as epilepsy and stroke. Such pH changes are known to
      exert profound effects on neuronal activity and survival. Heteromeric KCNQ2/3
      potassium channels constitute a potential target for modulation by H+ ions as
      they are expressed widely within the CNS and have been proposed to underlie the M
      current, an important determinant of excitability in neuronal cells. Whole-cell
      and single-channel recordings demonstrated a modulation of heterologously
      expressed KCNQ2/3 channels by extracellular H+ ions. KCNQ2/3 current was
      inhibited by H+ ions with an IC50 of 52 nM (pH 7.3) at -60 mV, rising to 2 microM
      (pH 5.7) at -10 mV. Neuronal M-current exhibited a similar sensitivity.
      Extracellular H+ ions affected two distinct properties of KCNQ2/3 current: the
      maximum current attainable upon depolarization (Imax) and the voltage dependence
      of steady-state activation. Reduction of Imax was antagonized by extracellular K+
      ions and affected by mutations within the outer-pore turret, indicating an outer
      pore based process. This reduction of Imax was shown to be due primarily to a
      decrease in the maximum open-probability of single KCNQ2/3 channels. Single
      channel open times were shortened by acidosis (pH 5.9), while closed times were
      increased. Acidosis also recruited a longer-lasting closed state, and caused a
      switch of single-channel activity from the full-conductance state ( approximately
      8 pS) to a subconductance state ( approximately 5 pS). A depolarizing shift in
      the activation curve of macroscopic KCNQ2/3 currents and single KCNQ2/3 channels
      was caused by acidosis, while alkalosis caused a hyperpolarizing shift.
      Activation and deactivation kinetics were slowed by acidosis, indicating specific
      effects of H+ ions on elements involved in gating. Contrasting modulation of
      homomeric KCNQ2 and KCNQ3 currents revealed that high sensitivity to H+ ions was
      conferred by the KCNQ3 subunit.

PMID- 14638936
TI  - Ligand-induced closure of inward rectifier Kir6.2 channels traps spermine in the
      pore.
AB  - Small organic amines block open voltage-gated K+ channels and can be trapped by
      subsequent closure. Such studies provide strong evidence for voltage gating
      occurring at the intracellular end of the channel. We engineered the necessary
      properties (long block times with unblock kinetics comparable to, or slower than,
      the kinetics of gating) into spermine-blocked, ATP-gated (N160D,L157C) mutant
      KATP channels, in order to test the possibility of "blocker trapping" in ligand
      gated Kir channels. Spermine block of these channels is very strongly voltage
      dependent, such that, at positive voltages, the off-rate of spermine is very low.
      A brief pulse to negative voltages rapidly relieves the block, but no such relief
      is observed in ATP-closed channels. The results are well fit by a simple kinetic
      model that assumes no spermine exit from closed channels. The results
      incontrovertibly demonstrate that spermine is trapped in channels that are closed
      by ATP, and implicate the M2 helix bundle crossing, or somewhere lower, as the
      probable location of the gate.

PMID- 14638937
TI  - Genetic engineering of the glyoxalase pathway in tobacco leads to enhanced
      salinity tolerance.
AB  - The glyoxalase pathway involving glyoxalase I (gly I) and glyoxalase II (gly II)
      enzymes is required for glutathione-based detoxification of methylglyoxal. We had
      earlier indicated the potential of gly I as a probable candidate gene in
      conferring salinity tolerance. We report here that overexpression of gly I+II
      together confers improved salinity tolerance, thus offering another effective
      strategy for manipulating stress tolerance in crop plants. We have overexpressed
      the gly II gene either alone in untransformed plants or with gly I transgenic
      background. Both types of these transgenic plants stably expressed the foreign
      protein, and the enzyme activity was also higher. Compared with nontransformants,
      several independent gly II transgenic lines showed improved capability for
      tolerating exposure to high methylglyoxal and NaCl concentration and were able to
      grow, flower, and set normal viable seeds under continuous salinity stress
      conditions. Importantly, the double transgenic lines always showed a better
      response than either of the single gene-transformed lines and WT plants under
      salinity stress. Ionic measurements revealed higher accumulation of Na+ and K+ in
      old leaves and negligible accumulation of Na+ in seeds of transgenic lines as
      compared with the WT plants. Comparison of various growth parameters and seed
      production demonstrated that there is hardly any yield penalty in the double
      transgenics under nonstress conditions and that these plants suffered only 5%
      loss in total productivity when grown in 200 mM NaCl. These findings establish
      the potential of manipulation of the glyoxalase pathway for increased salinity
      tolerance without affecting yield in crop plants.

PMID- 14638938
TI  - Contribution of astrocytes to hippocampal long-term potentiation through release
      of D-serine.
AB  - Repetitive correlated activation of pre- and postsynaptic neurons induced long
      term potentiation (LTP) of synaptic transmission among hippocampal neurons grown
      on a layer of astrocytes (mixed cultures) but not among neurons cultured in glial
      conditioned medium. Supplement of D-serine, an agonist for the glycine-binding
      site of N-methyl-D-aspartate (NMDA) receptors, enhanced NMDA receptor activation
      and enabled LTP induction in glial conditioned medium cultures. The induction of
      LTP in both mixed cultures and hippocampal slices was suppressed by NMDA receptor
      antagonists, glycine-binding-site blockers of NMDA receptors, or an enzyme that
      degrades endogenous D-serine. By providing extracellular D-serine that
      facilitates activation of NMDA receptors, astrocytes thus play a key role in long
      term synaptic plasticity.

PMID- 14638939
TI  - A microfluidic model for single-cell capillary obstruction by Plasmodium
      falciparum-infected erythrocytes.
AB  - Severe malaria by Plasmodium falciparum is a potentially fatal disease,
      frequently unresponsive to even the most aggressive treatments. Host organ
      failure is associated with acquired rigidity of infected red blood cells and
      capillary blockage. In vitro techniques have played an important role in modeling
      cell deformability. Although, historically they have either been applied to bulk
      cell populations or to measure single physical parameters of individual cells. In
      this article, we demonstrate the unique abilities and benefits of elastomeric
      microchannels to characterize complex behaviors of single cells, under flow, in
      multicellular capillary blockages. Channels of 8-, 6-, 4-, and 2-microm widths
      were readily traversed by the 8 microm-wide, highly elastic, uninfected red blood
      cells, as well as by infected cells in the early ring stages. Trophozoite stages
      failed to freely traverse 2- to 4-microm channels; some that passed through the 4
      microm channels emerged from constricted space with deformations whose shape
      recovery could be observed in real time. In 2-microm channels, trophozoites
      mimicked "pitting," a normal process in the body where spleen beds remove
      parasites without destroying the red cell. Schizont forms failed to traverse even
      6-microm channels and rapidly formed a capillary blockage. Interestingly,
      individual uninfected red blood cells readily squeezed through the blockages
      formed by immobile schizonts in a 6-microm capillary. The last observation can
      explain the high parasitemia in a growing capillary blockage and the well known
      benefits of early blood transfusion in severe malaria.

PMID- 14638940
TI  - Adhesive-cohesive model for protein compressibility: an alternative perspective
      on stability.
AB  - As a dynamic property of folded proteins, protein compressibility provides
      important information about the forces that govern structural stability. We
      relate intrinsic compressibility to stability by using molecular dynamics to
      identify a molecular basis for the variation in compressibility among globular
      proteins. We find that excess surface charge accounts for this variation not only
      for the proteins simulated by molecular dynamics but also for a larger set of
      globular proteins. This dependence on charge distribution forms the basis for an
      adhesive-cohesive model of protein compressibility in which attractive forces
      from solvent compete with tertiary interactions that favor folding. Further, a
      newly recognized correlation between compressibility and the heat capacity of
      unfolding infers a link between compressibility and the enthalpy of unfolding.
      This linkage, together with the adhesive-cohesive model for compressibility,
      leads to the conclusion that folded proteins can gain enthalpic stability from a
      uniform distribution of charged atoms, as opposed to partitioning charge to the
      protein surface. Whether buried charged groups can be energetically stabilizing
      is a fundamental, yet controversial, question regarding protein structure. The
      analysis reported here implies that one mechanism to gain enthalpic stability
      involves positioning charge inside the protein in an optimal structural
      arrangement.

PMID- 14638941
TI  - Interpulse growth hormone secretion in the episodic plasma profile causes the sex
      reversal of cytochrome P450s in senescent male rats.
AB  - Humans as well as other mammals experience an aging-related decline in drug
      metabolism as well as a diminution in growth hormone secretion. In the case of
      rats, these events are more pronounced in senescent males, whose expression of
      male-specific isoforms of cytochrome P450, the major drug-metabolizing enzymes
      and constituting approximately 60-70% of the total cytochrome P450 in male rat
      liver, is completely suppressed, whereas female-dependent isoforms are remarkably
      induced to female-like levels. Overlooked in these independently reported studies
      is the fact that "signals" inherent in the masculine episodic and female
      continuous growth hormone profiles regulate expression and/or suppression of the
      dozen or so sex-dependent cytochrome P450 isoforms in rat liver. Whereas previous
      studies identified profound reductions in the pulse amplitudes of the masculine
      growth hormone profile as the cause for the diminished hormone secretion during
      aging, pulse heights are not recognized by the cytochromes as regulatory signals.
      Instead, we have shown that just a nominal secretion of growth hormone during the
      usual growth hormone-devoid interpulse period in the masculine episodic profile
      can explain the complete repression of male-specific CYP2C11, CYP3A2, and CYP2A2
      and induction of female-dependent CYP2C12, CYP2C6, and CYP2A1 observed in
      senescent male rats.

PMID- 14638942
TI  - Food-web constraints on biodiversity-ecosystem functioning relationships.
AB  - The consequences of biodiversity loss for ecosystem functioning and ecosystem
      services have aroused considerable interest during the past decade. Recent work
      has focused mainly on the impact of species diversity within single trophic
      levels, both experimentally and theoretically. Experiments have usually showed
      increased plant biomass and productivity with increasing plant diversity. Changes
      in biodiversity, however, may affect ecosystem processes through trophic
      interactions among species as well. An important current challenge is to
      understand how these trophic interactions affect the relationship between
      biodiversity and ecosystem functioning. Here we present a mechanistic model of an
      ecosystem with multiple trophic levels in which plants compete for a limiting
      soil nutrient. In contrast to previous studies that focused on single trophic
      levels, we show that plant biomass does not always increase with plant diversity
      and that changes in biodiversity can lead to complex if predictable changes in
      ecosystem processes. Our analysis demonstrates that food-web structure can
      profoundly influence ecosystem properties.

PMID- 14638943
TI  - Atomically detailed folding simulation of the B domain of staphylococcal protein
      A from random structures.
AB  - The conformational space of the 10-55 fragment of the B-domain of staphylococcal
      protein A has been investigated by using the electrostatically driven Monte Carlo
      (EDMC) method. The ECEPP/3 (empirical conformational energy program for peptides)
      force-field plus two different continuum solvation models, namely SRFOPT (Solvent
      Radii Fixed with atomic solvation parameters OPTimized) and OONS (Ooi, Oobatake,
      Nemethy, and Scheraga solvation model), were used to describe the conformational
      energy of the chain. After an exhaustive search, starting from two different
      random conformations, three of four runs led to native-like conformations.
      Boltzmann-averaged root-mean-square deviations (RMSD) for all of the backbone
      heavy atoms with respect to the native structure of 3.35 A and 4.54 A were
      obtained with SRFOPT and OONS, respectively. These results show that the protein
      folding problem can be solved at the atomic detail level by an ab initio
      procedure, starting from random conformations, with no knowledge except the amino
      acid sequence. To our knowledge, the results reported here correspond to the
      largest protein ever folded from a random conformation by an initial-value
      formulation with a full atomic potential, without resort to knowledge-based
      information.

PMID- 14638944
TI  - Reduction of lipocalin-type prostaglandin D synthase in the preoptic area of
      female mice mimics estradiol effects on arousal and sex behavior.
AB  - In female rodents, sleep and activity levels fluctuate over the estrous cycle.
      When estradiol (E2) levels are highest, sleep is reduced whereas locomotion is
      increased. The preoptic area (POA) is a key site for estrogenic regulation of
      these functions. However, molecular mechanisms by which E2 acts to reduce sleep
      and increase activity are unclear. Recently, we demonstrated a twofold reduction
      in lipocalin-type prostaglandin D synthase (L-PGDS) transcript levels, after E2
      treatment, in the ventrolateral POA (VLPO), a putative sleep-active nucleus.
      Catalytic activity of L-PGDS produces PGD2, an endogenous somnogen. Thus, we
      hypothesized that decreases in PGD2 in the VLPO may contribute to the generalized
      arousal mediated by estrogens. To test this, we infused (i) antisense
      oligonucleotides (oligos), containing locked nucleic acid moieties (an improved
      technology), targeted to L-PGDS mRNA, (ii) scrambled sequence control oligos, or
      (iii) saline vehicle into the VLPO of ovariectomized female mice treated with E2
      or oil. Arousal states and activity levels were assessed in response to a series
      of sensory stimuli (vestibular, olfactory, and somatosensory). The vestibular
      stimulus, which was administered first, resulted in the strongest responses and
      elicited significantly different responses among the groups: all groups in the E2
      cohort demonstrated increases in overall home cage activity and duration of that
      activity compared with the oil-treated control groups. As predicted from E2
      suppression of L-PGDS transcript levels, the responses of the locked nucleic acid
      antisense oligo-treated animals from the oil cohort did not differ from the E2
      treated groups, such that they also demonstrated increases in activity and
      duration of activity compared with their controls. Thus, reducing L-PGDS in the
      VLPO of oil-treated females mimicked the effect of E2 on activity and arousal and
      represents a unique molecular pathway through which E2 may modulate these
      functions.

PMID- 14638945
TI  - Hox cluster duplications and the opportunity for evolutionary novelties.
AB  - Hox genes play a key role in animal body plan development. These genes tend to
      occur in tightly linked clusters in the genome. Vertebrates and invertebrates
      differ in their Hox cluster number, with vertebrates having multiple clusters and
      invertebrates usually having only one. Recent evidence shows that vertebrate Hox
      clusters are structurally more constrained than invertebrate Hox clusters; they
      exclude transposable elements, do not undergo tandem duplications, and conserve
      their intergenic distances and gene order. These constraints are only relaxed
      after a cluster duplication. In contrast, invertebrate Hox clusters are
      structurally more plastic; tandem duplications are common, the linkage of Hox
      genes can change quickly, or they can lose their structural integrity completely.
      We propose that the constraints on vertebrate Hox cluster structure lead to an
      association between the retention of duplicated Hox clusters and adaptive
      radiations. After a duplication the constraints on Hox cluster structure are
      temporarily lifted, which opens a window of evolvability for the Hox clusters. If
      this window of evolvability coincides with an adaptive radiation, chances are
      that a modified Hox cluster becomes recruited in an evolutionary novelty and then
      both copies of duplicated Hox clusters are retained.

PMID- 14638946
TI  - Infectious endocarditis and stroke: any lessons learned since William Osler's
      Gulstonian lectures?

PMID- 14638948
TI  - REM sleep behavior disorder: a dopaminergic deficiency disorder?

PMID- 14638949
TI  - Echo of silence: silent mutations, RNA splicing, and neuromuscular diseases.

PMID- 14638950
TI  - The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis:
      report of the Therapeutics and Technology Assessment Subcommittee of the American
      Academy of Neurology.
AB  - Mitoxantrone is the first drug approved for the treatment of secondary
      progressive multiple sclerosis (SPMS) in the United States. This assessment
      considers use of mitoxantrone in the treatment of MS. Mitoxantrone probably
      reduces the clinical attack rate and reduces attack-related MRI outcomes in
      patients with relapsing MS (Type B recommendation). Also, mitoxantrone may have a
      beneficial effect on disease progression in patients with MS whose clinical
      condition is worsening (Type B recommendation). The potential for serious
      toxicity of mitoxantrone, however, must be taken into account when considering
      this therapy in individual patients. Moreover, because the potential clinical
      benefits on disease progression appear to be only modest, the results of the
      single phase III trial should be replicated in another (and hopefully much
      larger) clinical study before this agent is widely recommended for the treatment
      of patients with MS.

PMID- 14638952
TI  - Stroke location, characterization, severity, and outcome in mitral vs aortic
      valve endocarditis.
AB  - OBJECTIVE: To characterize the incidence and clinical features of patients with
      infective endocarditis (IE) and stroke. METHODS: The authors reviewed the records
      of 707 patients diagnosed with definite or possible IE between January 1984 and
      November 1999. Stroke was confirmed by application of strict definitions and
      classified by type, pathophysiology, vascular territory, and severity. The
      authors determined mortality rates for the initial hospitalization and 12 months
      after admission. RESULTS: Strokes occurred in 68 (9.6%) of 707 patients with IE,
      38 (17%) of 218 patients with mitral valve endocarditis (MVE), 14 (9%) of 149
      patients with aortic valve endocarditis (AVE), and 16 (5%) of 340 patients with
      other forms of IE (OR for MVE vs AVE = 2.0, 95% CI 1.1 to 3.9). Among the
      patients with MVE or AVE and stroke, there were no significant relationships
      between site of vegetation and length of hospitalization, stroke severity,
      mortality during the initial hospitalization, or 12-month mortality. Fifty-two
      percent of patients with stroke and IE died within 1 year of admission.
      CONCLUSIONS: The overall incidence of stroke in patients with IE (9.6%) is lower
      than previous reports (21 to 39%). Patients with MVE had a greater risk of stroke
      than patients with AVE. Fifty-two percent of patients died within 1 year of
      admission for IE.

PMID- 14638953
TI  - Risk of stroke and recurrent dissection after a cervical artery dissection: a
      multicenter study.
AB  - OBJECTIVE: To assess the risk of stroke, TIA, or dissection recurrence after a
      first event of cervical artery dissection (CAD). METHODS: The authors undertook a
      historical cohort study of consecutive patients with a first event of CAD who
      were admitted in 24 departments of neurology within a period of at least 1 year.
      Patients were retrospectively selected from a stroke data bank or from the local
      administrative data bank using the 10th revision of the International Statistical
      Classification of Diseases. A neurologist and a radiologist reviewed all charts
      to validate diagnosis and collect data. In 2002, patients were interviewed by
      phone or during a visit by the local investigators. RESULTS: Four hundred fifty
      nine patients (mean age 44.0 +/- 9.7 years) were included in the study. Among the
      457 survivors, 25 (5.5%) could not be contacted in 2002 because they had moved.
      After a mean follow-up of 31 months, four (0.9%) patients presented a recurrent
      ischemic stroke attributable to either not yet completely recovered initial CAD
      (n = 2) or a recurrent CAD (n = 2). Eight (1.8%) patients had a TIA without CAD
      recurrence. Two TIA occurred at the acute stage of CAD. Of the six remaining TIA,
      only one was associated with chronic arterial stenosis. In addition, two patients
      had recurrent CAD without stroke, giving a total of four (0.9%) CAD recurrences.
      CONCLUSIONS: Patients with a first event of CAD have a very low risk of ischemic
      events or dissection recurrences. Ischemic events seem rarely to be in relation
      with chronic arterial lesions.

PMID- 14638954
TI  - The influence of diabetes and hyperglycemia on clinical course after
      intracerebral hemorrhage.
AB  - OBJECTIVE: To determine whether diabetes and admission hyperglycemia in
      nondiabetic patients influence outcome and the occurrence of cerebral and medical
      complications after intracerebral hemorrhage (ICH). METHODS: The study sample
      included 764 patients with ICH. The effects of diabetes and admission
      hyperglycemia were examined in relation to 30-day and 3-month mortality using Cox
      regression models controlling for potential confounders. The analysis was
      conducted for the entire sample of patients and repeated in comatose and
      noncomatose patients. RESULTS: Among comatose patients, neither diabetes nor
      admission hyperglycemia contributed significant predictive information, as nearly
      all patients died. In noncomatose patients, diabetes was an independent predictor
      of 30-day (odds ratio [OR] 1.31; 95% CI 1.08 to 1.58) and 3-month (OR 1.30; 95%
      CI 1.08 to 1.56) mortality and was associated with a greater incidence of
      infectious (OR 1.24; 95% CI 1.03 to 1.49) and cerebral (OR 1.42; 95% CI 1.10 to
      1.83) complications. Among nondiabetic patients with Glasgow Coma Scale score of
      >8, hyperglycemia was an independent predictor of 30-day (OR 1.29; 95% CI 1.05 to
      1.58) and 3-month (OR 1.27; 95% CI 1.05 to 1.53) mortality and was associated
      with a greater incidence of cerebral complications (OR 1.47; 95% CI 1.12 to
      2.94). CONCLUSIONS: Both diabetes and admission hyperglycemia in nondiabetic
      patients are predictors of poor outcome after supratentorial ICH. This may be
      related to the greater incidence of cerebral and infectious complications in
      diabetic patients and of cerebral complications in hyperglycemic nondiabetic
      patients.

PMID- 14638955
TI  - Rate of cognitive decline and mortality in Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is associated with increased mortality, but
      survival in those with the disease varies widely. It is uncertain how much of the
      variation in survival is due to individual differences in rate of disease
      progression. METHODS: During a 4-year period, 354 persons with AD underwent
      annual clinical evaluations that included administration of 17 cognitive function
      tests, from which global and specific measures of cognitive function were
      derived. A growth curve approach was used to assess individual rates of cognitive
      decline and proportional hazards models adjusted for age, sex, and education to
      examine the associations of baseline level of cognition and rate of cognitive
      decline with mortality. RESULTS: During the 4-year study period, 242 persons
      survived and 112 died. At baseline, the global measure of cognition ranged from 
      1.68 to 1.36 (mean = 0.03, SD = 0.57), with higher scores indicating better
      function. Baseline level of cognition was not related to mortality (p = 0.12).
      Global cognition declined an average of 0.56 unit/year, with substantial
      heterogeneity (SD = 0.41). To determine mortality risk, persons were divided into
      quartiles based on rate of cognitive decline and survival contrasted in the
      quartile with the least decline with survival in each remaining quartile,
      adjusting for baseline level of cognition. Compared with those with the least
      decline, risk of death was increased more than threefold in the subgroup with
      mild decline, more than fivefold in those with moderately rapid decline, and more
      than eightfold in those with the most rapid decline. Similar results were found
      after controlling for baseline health and disability and in analyses using
      specific cognitive function measures. CONCLUSION: Mortality in AD is strongly
      associated with rate of cognitive decline.

PMID- 14638956
TI  - Myasthenia gravis: consequences for pregnancy, delivery, and the newborn.
AB  - OBJECTIVE: To investigate the effect of maternal myasthenia gravis (MG) on giving
      birth and on the newborn. METHODS: A retrospective cohort study for 1967 through
      2000 was undertaken, using data from the Medical Birth Registry of Norway, based
      on the compulsory notification of all births. The target group consisted of 127
      births by mothers with MG. The reference group consisted of all 1.9 million
      births by mothers without MG. RESULTS: Women with MG had a higher rate of
      complications at delivery (40.9% vs 32.9%, p = 0.05), and in particular the risk
      of preterm rupture of amniotic membranes was three times higher in the MG group
      compared to the reference group (5.5% vs 1.7%, p = 0.001). The rate of
      interventions during birth was raised (33.9% vs 20.0%, p < 0.001) and cesarean
      sections doubled (17.3% vs 8.6%, p = 0.001). Five children (3.9%) born by MG
      mothers had severe anomalies, and three of them died. CONCLUSIONS: MG is
      associated with an increased risk for complications during delivery. This is
      linked to a higher occurrence of interventions during birth.

PMID- 14638958
TI  - Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985
      2000.
AB  - BACKGROUND: Epidemiologic data for multiple sclerosis (MS) in Olmsted County, MN,
      have been recorded for almost 100 years and have indicated that the increasing
      prevalence rate was likely due in part to an increasing incidence rate. METHODS:
      All cases of MS diagnosed from 1985 to 2000 were identified using the centralized
      diagnostic index at the Mayo Clinic and the Rochester Epidemiology Program
      Project, a shared database of all medical practitioners in the county. Patients
      were required to have established residency at least 1 year prior to diagnosis of
      MS. Results were also age- and sex-adjusted to control for shifts in the
      population structure. RESULTS: The raw prevalence of MS was determined to be 177
      per 100,000 on December 1, 2000, and the raw incidence rate was 7.5 per 100,000
      person-years at risk from 1985 to 2000. CONCLUSIONS: After age and sex adjustment
      to a common population, these prevalence and incidence rates of MS appear to have
      been stable rather than increasing over the past 20 years.

PMID- 14638957
TI  - Contrast letter acuity as a visual component for the Multiple Sclerosis
      Functional Composite.
AB  - BACKGROUND: Visual dysfunction is one of the most common causes of disability in
      multiple sclerosis (MS). The Multiple Sclerosis Functional Composite (MSFC), a
      new clinical trial outcome measure, does not currently include a test of visual
      function. OBJECTIVE: To examine contrast letter acuity as a candidate visual
      function test for the MSFC. METHODS: Binocular contrast letter acuity testing
      (Sloan charts) was performed in a subgroup of participants from the International
      Multiple Sclerosis Secondary Progressive Avonex Controlled Trial (IMPACT
      Substudy) and in MS patients and disease-free control subjects from a cross
      sectional study of visual outcome measures (Multiple Sclerosis Vision Prospective
      cohort [MVP cohort]). High-contrast visual acuity was measured in both studies;
      MVP cohort participants underwent additional binocular testing for contrast
      sensitivity (Pelli-Robson chart), color vision (D-15 desaturated test), and
      visual field (Esterman test, Humphrey Field Analyzer II). RESULTS: Contrast
      letter acuity (Sloan charts, p < 0.0001, receiver operating characteristic curve
      analysis) and contrast sensitivity (Pelli-Robson chart, p = 0.003) best
      distinguished MS patients from disease-free control subjects in the MVP cohort.
      Correlations of Sloan chart scores with MSFC and Expanded Disability Statue Scale
      (EDSS) scores in both studies were significant and moderate in magnitude,
      demonstrating that Sloan chart scores reflect visual and neurologic dysfunction
      not entirely captured by the EDSS or MSFC. CONCLUSIONS: Among clinical measures,
      contrast letter acuity (Sloan charts) and contrast sensitivity (Pelli-Robson
      chart) demonstrate the greatest capacity to identify binocular visual dysfunction
      in MS. Sloan chart testing also captures unique aspects of neurologic dysfunction
      not captured by current EDSS or MSFC components, making it a strong candidate
      visual function test for the MSFC.

PMID- 14638959
TI  - Atypical cerebral laterality in adults with persistent developmental stuttering.
AB  - BACKGROUND: Two of the most consistent anatomic asymmetries found in the human
      brain are a larger right than left prefrontal and left than right occipital lobe.
      Reduced or reversed asymmetries of these regions are considered markers of
      atypical cerebral laterality, and atypical cerebral laterality has been proposed
      to increase neural risk for developmental stuttering. OBJECTIVE: S: To learn if
      atypical prefrontal and occipital lobe asymmetries are more common in adults who
      stutter vs fluent control subjects and to determine whether lobar size or
      asymmetry patterns are associated with stuttering severity or language abilities.
      METHODS: Adults with persistent developmental stuttering (n = 16) and matched
      control subjects (n = 16) had language and stuttering assessments. Subjects were
      also studied with volumetric MRI scans. Total hemisphere, prefrontal, and
      occipital lobe regions were measured, and volumes were calculated proportionally
      to hemisphere volume. RESULTS: Hemisphere and total brain volumes did not differ
      between the groups. Control subjects had the expected larger right than left
      prefrontal and larger left than right occipital lobe volume. In contrast, the
      adults who stutter did not have these asymmetries. Stuttering severity was not
      associated with specific anatomic configurations, whereas language-processing
      deficits in adults who stutter were associated with prefrontal and occipital
      volume reduction. CONCLUSIONS: Developmental stuttering is associated with
      atypical prefrontal and occipital lobe asymmetries. In addition, deficits in
      language processing were associated with some anatomic measures in the adults who
      stutter.

PMID- 14638960
TI  - Neurodevelopmental outcome after endovascular treatment of vein of Galen
      malformations.
AB  - OBJECTIVE: To assess neurodevelopmental outcome after endovascular treatment of
      vein of Galen malformations (VOGM). METHODS: Outcome of patients who underwent
      endovascular treatment for VOGM between 1983 and 2002 was assessed by chart
      review and parental questionnaires. Development was classified as normal, minor
      delay (slow initial acquisition of milestones but no permanent disability), or
      significant delay (slow or incomplete acquisition of milestones with some
      permanent disability) using an adaptation of the Denver Developmental
      Questionnaire. RESULTS: Twenty-seven patients were identified: five presented
      prenatally (by ultrasound), 16 as neonates, and 6 after the neonatal period. The
      most common presenting features were congestive heart failure (CHF; 16/27) and
      hydrocephalus (8/27). The 16 patients with CHF all presented either prenatally or
      neonatally; 4 died acutely, 6 had significant delay, and 6 had no or minor
      developmental delay. Of those presenting in the perinatal period without CHF, all
      survived, two of five were significantly delayed, and three of five had no delay.
      Of those presenting after the neonatal period, all survived and only one of six
      had delay. By angiographic classification, outcome was worse for those with
      choroidal VOGM (3/13 died; 5/13 had significant delay) than for those with mural
      VOGM (2/10 had significant delay; none died). For the entire series, 52% of all
      cases (61% of survivors) had no or minor delay. CONCLUSIONS: Fourteen of 27
      children who received treatment for VOGM had a favorable outcome. Features
      associated with worse outcome were perinatal presentation, presence of CHF, and
      choroidal angioarchitecture.

PMID- 14638961
TI  - Two phases of HIV RNA decay in CSF during initial days of multidrug therapy.
AB  - BACKGROUND: Defining cellular and tissue sources of HIV-1 in CSF is important for
      understanding disease pathogenesis and optimal therapies for HIV infection in the
      brain. OBJECTIVE: To identify the time of maximal viral decay in CSF during the
      initial days of antiretroviral therapy. METHODS: Serial CSF and plasma data were
      available from four adults who underwent ultraintensive CSF sampling for 48 hours
      at baseline and again beginning 72 hours after starting antiretroviral therapy.
      Regression lines were generated using HIV-1 RNA data from 17 on-treatment serial
      CSF samples obtained at 3-hour intervals. Viral RNA was quantified by Nuclisens
      and Amplicor HIV-1 Monitor assays. RESULTS: Extrapolation of regression lines
      intersected baseline below actual baseline CSF HIV-1 RNA concentrations,
      indicating that virus decayed most rapidly on days 1 through 3 with half-lives of
      no more than 0.9 to 2.8 days. Half-lives on days 4 and 5 ranged from 1.3 to 4.9
      days. Plasma data also showed early rapid decay. CONCLUSIONS: Multiple phases of
      viral decay suggest that virus in CSF originates from at least two sources during
      untreated, asymptomatic HIV-1 infection. The short half-life indicates that the
      primary source is CD4+ T cells. Sampling during days 1 through 3 and different
      stages of disease will better define sources of virus.

PMID- 14638962
TI  - Molecular analysis of astrocytomas presenting after age 10 in individuals with
      NF1.
AB  - BACKGROUND: Fifteen to 20% of children with neurofibromatosis type 1 (NF1)
      develop low-grade astrocytomas. Although brain tumors are less common in
      teenagers and adults with NF1, recent studies have suggested that patients with
      NF1 are at a significantly increased risk of developing astrocytomas. OBJECTIVE:
      S: To investigate the genetic basis for astrocytoma development in patients with
      NF1 beyond the first decade of life. METHODS: The authors performed molecular
      genetic analyses of 10 NF1-associated astrocytomas representing all World Health
      Organization (WHO) malignancy grades using fluorescence in situ hybridization,
      loss of heterozygosity, immunohistochemistry, and direct sequencing. RESULTS:
      Later-onset NF1-associated astrocytomas, unlike histologically identical sporadic
      astrocytomas, exhibit NF1 inactivation, supporting a direct association with NF1
      rather than a chance occurrence. Furthermore, some of these astrocytomas have
      homozygous NF1 deletion. In addition, genetic changes observed in high-grade
      sporadic astrocytomas, including TP53 mutation and CDKN2A/p16 deletion, are also
      seen in NF1-associated high-grade astrocytomas. CONCLUSIONS: Neurofibromatosis
      type 1-associated astrocytomas occurring in patients older than 10 years exhibit
      genetic changes observed in sporadic high-grade astrocytomas. Patients with
      neurofibromatosis type 1 and germline NF1 deletions may be at risk for developing
      late-onset astrocytomas.

PMID- 14638963
TI  - Vagus nerve stimulation for essential tremor: a pilot efficacy and safety trial.
AB  - OBJECTIVE: To assess the safety and efficacy of vagus nerve stimulation (VNS) for
      essential tremor (ET). METHODS: This was a pilot open-treatment trial at three
      centers, with masked videotape tremor assessments. Inclusion required a severity
      score of 3 or 4 on the Tremor Rating Scale (TRS) in one or both hands. At
      baseline, tremor was assessed with TRS and Unified Tremor Rating Assessment
      (UTRA), accelerometry, and a videotape protocol. The VNS device was implanted
      with leads placed around the left cervical vagus nerve. Stimulation was adjusted
      over 4 weeks before the repeat tremor assessments. Two raters masked to the study
      visit scored the videotapes. RESULTS: Nine subjects participated, with a mean age
      of 65 years and a mean age at onset of tremor of 24. Investigators rated hand
      tremor as mildly improved (TRS 2.3 +/- 0.7 during VNS vs 3.0 +/- 0.4 during
      baseline, p = 0.06). Accelerometry-measured total power improved 50.2 +/- 31.8%
      (p < 0.01). Videotape tremor scores were highly correlated between the masked
      raters and revealed no changes in tremor scores with treatment. VNS was well
      tolerated, with the most common adverse events being stimulation related.
      CONCLUSIONS: VNS was judged by investigators to mildly improve upper extremity
      tremor. This finding was not confirmed in videotape scoring by masked raters. VNS
      is not likely to have a clinically meaningful effect on ET.

PMID- 14638965
TI  - Cesare Lombroso, cortical dysplasia, and epilepsy: keen findings and odd
      theories.
AB  - BACKGROUND: Cesare Lombroso supported a common origin of criminality, genius, and
      epilepsy as caused by factors impairing the embryonic development of the CNS,
      mainly affecting the hierarchically superior neural centers. OBJECTIVE: To
      describe the first observations of cortical dysplasia in patients with epilepsy
      by Cesare Lombroso and his coworkers in 1896. RESULTS: To confirm his theories,
      Lombroso emphasized the need for the direct observation of the patient, using
      anthropologic, social, neurophysiologic, economic, and pathologic data. With the
      collaboration of his pupil Luigi Roncoroni, Lombroso described a prevalence of
      large, giant pyramidal neurons and polymorphous cells through the gray matter of
      the frontal cortex in 13 patients with epilepsy. Most of the large pyramidal
      neurons were haphazardly arranged, presenting also an abnormal orientation of
      their apical dendrites. The number of nervous cells was noticeably reduced, with
      the presence of abundant gliosis. Moreover, the granular layers were dramatically
      reduced or absent in most patients, and numerous nervous cells were present in
      the subcortical white matter. This particular finding was never observed in
      specimens from criminal and healthy control subjects. Lombroso and Roncoroni
      explained their finding as evidence of an arrest of CNS development. CONCLUSIONS:
      More than one century ago, Cesare Lombroso and collaborators described
      developmental lesions in the frontal cortex of patients with epilepsy, which
      correspond to what currently is called Taylor's dysplasia. However, they used
      their observations to support their scientific misconception on the relationship
      between criminality, epilepsy, and genius.

PMID- 14638964
TI  - Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain
      resections.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus, is the
      causative agent of roseola infantum and has been associated with a number of
      neurologic disorders including seizures, encephalitis/meningitis, and multiple
      sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully
      defined, a number of studies have suggested that the CNS can be a site for
      persistent HHV-6 infection. OBJECTIVE: To characterize the extent and
      distribution of HHV-6 in human glial cells from surgical brain resections of
      patients with mesial temporal lobe epilepsy (MTLE). METHOD: Brain samples from
      eight patients with MTLE and seven patients with neocortical epilepsy (NE)
      undergoing surgical resection were quantitatively analyzed for the presence of
      HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also
      characterized by western blot analysis and in situ immunohistochemistry (IHC). In
      addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary
      acidic protein (GFAP) by double immunofluorescence. RESULTS: DNA obtained from
      four of eight patients with MTLE had significantly elevated levels of HHV-6 as
      quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients
      with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in
      hippocampal sections (up to 23,079 copies/10(6) cells) and subtyped as HHV-6B.
      Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co
      localized to GFAP-positive cells that morphologically appeared to be astrocytes.
      CONCLUSIONS: HHV-6B is present in brain specimens from a subset of patients with
      MTLE and localized to astrocytes in the absence of inflammation. The
      amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE
      warrants further investigation into the possible role of HHV-6 in the development
      of MTLE.

PMID- 14638966
TI  - Sixth nerve palsy in nasopharyngeal carcinoma.

PMID- 14638967
TI  - The effects of pramipexole in REM sleep behavior disorder.
AB  - The authors evaluated the effects of pramipexole, a dopaminergic D2-D3 receptor
      agonist, on eight patients with idiopathic REM sleep behavior disorder. Five
      patients reported a sustained reduction in the frequency or intensity of sleep
      motor behaviors, which was confirmed by video recording, although no change was
      observed for the percentage of phasic EMG activity during REM sleep.
      Surprisingly, a decrease in the percentage of time spent with REM sleep muscle
      atonia was observed with treatment. The treatment did not modify the indexes of
      periodic leg movements.

PMID- 14638968
TI  - Endovascular embolectomy of acute basilar artery occlusion.
AB  - Acute basilar artery occlusion has a mortality rate approaching 90%. The authors
      describe a case of acute basilar artery occlusion managed successfully with
      endovascular embolectomy. A 31-year-old man sought treatment for confusion,
      dysarthria, and right-sided weakness. He soon became unresponsive and was found
      to have a vertebral artery dissection and an associated basilar artery embolism.
      The dissection was managed with endovascular stenting, and the basilar artery
      embolus was removed with a clot retriever at 7 hours. The patient recovered
      without neurologic deficit.

PMID- 14638969
TI  - Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz
      syndromes are allelic.
AB  - The authors describe a patient with hypoprebetalipoproteinemia, acanthocytosis,
      retinitis pigmentosa, and pallidal degeneration (HARP) who has two compound
      heterozygote mutations of the PANK2 gene. IVS4-1 G>T segregates with the lipid
      and erythrocyte changes in the mother and sister. No other family members have
      the lipid, erythrocyte, or clinical abnormalities. The father and two brothers
      are heterozygous for Met327Thr. One other mutation has been found in this PANK2
      region associated with the HARP phenotype, suggesting a local genotype effect.

PMID- 14638970
TI  - CSF hypocretin-1 levels in restless legs syndrome.
AB  - CSF hypocretin-1 levels at 6 PM did not significantly differ between patients
      with restless legs syndrome (RLS) and control subjects as measured by direct
      radioimmunoassay and after acid extraction. The authors did not observe
      significant differences between early onset and late onset RLS. Hypocretin-1
      levels did not correlate with RLS severity or polysomnographic measures. These
      results contrast with previous findings reporting significantly increased CSF
      hypocretin-1 in the late evening and mostly in early onset RLS.

PMID- 14638971
TI  - Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism.
AB  - The DJ-1 gene was identified as responsible for early onset autosomal recessive
      parkinsonism in two families (PARK7). In this study, after excluding mutations in
      the parkin gene, the authors screened a large series of early onset autosomal
      recessive parkinsonism families and consanguineous isolated patients of diverse
      geographic origins for DJ-1 mutations. No mutations were found. This indicates
      that PARK7 is not a common locus for early onset autosomal recessive
      parkinsonism, and that one or more new loci remains to be identified.

PMID- 14638972
TI  - Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle
      disease.
AB  - The authors report the molecular findings in a patient with McArdle disease who
      harbored a silent polymorphism (K608K) in the myophosphorylase gene. cDNA studies
      demonstrated that this polymorphism leads to a severe mosaic alteration in mRNA
      splicing, including exon skipping, activation of cryptic splice-sites, and exon
      intron reorganizations. These findings suggest that, in patients with McArdle
      disease in whom no pathogenic mutation has been found, any a priori silent
      polymorphism should be re-evaluated as a putative splicing mutation.

PMID- 14638973
TI  - Late onset Charcot-Marie-Tooth 2 syndrome caused by two novel mutations in the
      MPZ gene.
AB  - MPZ gene mutations cause demyelinating and axonal Charcot-Marie-Tooth (CMT)
      disease. Two novel MPZ mutations are reported in very late onset and progressive
      CMT syndrome. The N60H caused axonal CMT in a large family, whereas the I62M
      occurred in a single patient presenting with a primary axonal neuropathy.
      Previously, chronic polyradiculoneuritis was assumed in two patients. Molecular
      genetic testing and particularly screening for MPZ mutations in late onset
      neuropathies are important to differentiate acquired and inherited neuropathies.

PMID- 14638974
TI  - Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and
      tolerability.
AB  - The authors report a retrospective analysis of the use of mycophenolate mofetil
      (MyM) in 85 patients with autoimmune myasthenia gravis. The Myasthenia Gravis
      Foundation of America (MGFA) postintervention status (PIS) was used to
      characterize the treatment response in each patient. Sixty-two patients (73%)
      achieved a PIS status indicating improvement. Quantitative strength testing
      performed on the majority of patients before and after treatment also improved.
      Side effects to MyM were observed in 27% of patients but required discontinuation
      in only 6%.

PMID- 14638976
TI  - An improved ELISA for screening for neutralizing anti-IFN-beta antibodies in MS
      patients.
AB  - A reliable screening assay for anti-interferon beta (IFNbeta) antibodies is
      needed for patients with multiple sclerosis (MS) receiving IFNbeta therapy. The
      performance of a new ELISA method, the capture ELISA (cELISA), was assessed by
      comparing it to a standard IFNbeta ELISA in correlating with neutralizing
      antibodies measurement in 453 sera from patients with MS. The cELISA outperformed
      the standard ELISA, and may be a suitable screening assay for anti-IFNbeta
      antibodies in IFNbeta-treated patients with MS.

PMID- 14638975
TI  - Intergenerational instability and marked anticipation in SCA-17.
AB  - The authors describe an Italian family with autosomal dominant ataxia, dementia,
      psychiatric and extrapyramidal features, epilepsy, mild sensorimotor axonal
      neuropathy, and MRI findings of cerebral and cerebellar atrophy. A child had a
      distinctive presentation with onset at 3 years, growth retardation, fast
      progression, and early death. Molecular analysis demonstrated an expanded CAG/CAA
      repeat in the TBP gene (SCA-17). The repeat size was 66 triplets in the child and
      53 in all the other patients.

PMID- 14638977
TI  - 1 Hz rTMS enhances extrastriate cortex activity in migraine: evidence of a
      reduced inhibition?
AB  - We recently reported a paradoxical facilitatory effect of 1 Hz repetitive TMS
      (rTMS) on the primary visual cortex in migraine possibly due to the failure of
      inhibitory circuits, unable to be upregulated by low frequency rTMS. To
      investigate if inhibitory circuit dysfunction extends beyond striate cortex in
      migraine with aura, we studied the effects of 1 Hz rTMS over the right
      extrastriate cortex on perception of illusory contours in these patients. Low
      frequency rTMS enhanced activity of extrastriate cortex in migraineurs, speeding
      up reaction times on illusory contour perception. This finding supports the view
      of a failure of inhibitory circuits also involving the extrastriate cortex in
      migraine with aura.

PMID- 14638978
TI  - MRI after thoracic epidural blood patch.

PMID- 14638979
TI  - MR imaging and post LP headache.

PMID- 14638980
TI  - Levodopa addiction in non-parkinsonian patients.

PMID- 14638981
TI  - Severe worsening of parkinsonism in Lewy body dementia due to donepezil.

PMID- 14638982
TI  - Pallidotomy for severe generalized chorea of juvenile-onset dentatorubral
      pallidoluysian atrophy.

PMID- 14638983
TI  - Stool-withholding activity mimicking epilepsy.

PMID- 14638984
TI  - Knowledge and management of transient ischemic attacks among US primary care
      physicians.

PMID- 14638985
TI  - Isopropanol intoxication mimicking basilar artery thrombosis.

PMID- 14638986
TI  - Hereditary neuropathy with liability to pressure palsies mimicking hypoglossal
      nerve injuries.

PMID- 14638987
TI  - Isolated shoulder paresis caused by a small cortical infarction.

PMID- 14638988
TI  - Patient page. The effect of myasthenia gravis on pregnancy and the newborn.

PMID- 14638989
TI  - CSF hypovolemia vs intracranial hypotension in "spontaneous intracranial
      hypotension syndrome".

PMID- 14638990
TI  - Facial hemangioma and cerebral corticovascular dysplasia: a syndrome associated
      with epilepsy.

PMID- 14638991
TI  - Agonists versus levodopa in PD: the thrilla of whitha.

PMID- 14638992
TI  - Rate of Helicobacter pylori infection in children and clonality of Taiwan
      strains.
AB  - The infection rate of Helicobacter pylori in children from < 1 to 17 years old
      was investigated. Three techniques, namely culture, CLO test, and PCR, were
      employed to check the presence or absence of the organism in the antrum of the
      stomach. Several PCR positives without viable cultures were observed in babies of
      less than one year old. On the other hand, only two viable cultures were obtained
      from toddlers of less than two years old. The percentage of positive cultures
      steadily increased from 8% (3 of 42 cases) in the 0-4 years old age group to 32%
      (32 of 99 cases) in the 13-17 years old age group. A steady increase also was
      observed in the result of the CLO test. In PCR, the percentage of positives was
      greatly higher than that seen with the culture or CLO test. The rate of PCR
      positives also showed an increase with age but of a much slower rate. The overall
      infection rate in 295 children was 22% (64 of 295 cases) positive with culture
      and 76% (225 of 295 cases) with PCR, in contrast to 85% (40 of 49 cases) and 92%
      (43 of 47 cases), respectively, in adults. The urease activity of the H. pylori
      derived from children was much lower than that derived from adults (P < 0.001).
      Taken together, these results suggest that a child might be repeatedly infected
      and some infecting strains eventually might obtain a steady infection, perhaps by
      a strain of higher virulence such as higher urease activity. The base variations
      in the nucleotide sequences did not correlate to the varied urease activities or
      to the age of the child. The sequences, however, indicated that there were two
      types of strains. The strains in Taiwan appeared to be derived from the French
      type strain and not the English type strain. The amino acid sequences of the ureA
      and the phylogenetic relationship of the 29 strains indicated that the strains in
      Taiwan are rapidly evolving into a unique clone.

PMID- 14638993
TI  - Phylogenetic analysis of spotted fever group rickettsiae based on gltA, 17-kDa,
      and rOmpA genes amplified by nested PCR from ticks in Japan.
AB  - In order to understand the natural situation of rickettsiae in the ticks in
      Japan, the rickettsial genes, gltA gene, rOmpA gene, and 17-kDa gene, were
      amplified from the ticks by nested PCR. The prevalences of rickettsial gltA genes
      among Haemaphysalis formosensis, H. longicornis, H. megaspinosa, Ixodes ovatus,
      H. flava, H. kitaokai, and I. persulcatus were 62, 57, 24, 24, 19, 13, and 10%,
      respectively; 26% (186/722) being the average. The gltA genes amplified from the
      ticks were classified into 9 genotypes (I to IX) by the difference in nucleotide
      sequences. Genotype I was detected from 7 species of ticks. Genotype II mainly
      was detected from H. longicornis and H. formosensis. Genotypes III and VII mainly
      were detected from H. flava and I. ovatus. The polarization in the distribution
      of genotypes among regions where the ticks were collected was not clear. Based on
      the phylogenetic analysis of the three genes presented here, genotypes I, III,
      and IV (detected from H. formosensis, H. hystricia, and I. ovatus ) are
      genetically close with each other, but rickettsiae of the same property still
      have not been isolated from ticks anywhere in the world. These genotypes should
      be considered as new species among SFG rickettsiae. Genotype II was identical
      with strain FUJ-98, genetically close to R. japonica which has been isolated from
      ticks in China. Genotype V was identical with R. felis and strain California 2
      isolated from the cat flea. This is the first report on the detection of R. felis
      from ticks. Genotype VI detected from Ixodes sp. did not seem to belong to genus
      Rickettsia. Based on the previous antigenic data and the phylogenetic analysis
      presented here, Genotype VII should be considered a variant of R. helvetica and
      genotype VIII detected from I. ovatus and I. persulcatus were identical with R.
      helvetica. Genotype IX detected from I. nipponensis was genetically close to the
      strains IRS3, IRS4, and IrR/Munich isolated from I. ricinus in Slovakia and
      German.

PMID- 14638994
TI  - Effects of quorum sensing on flaA transcription and autoagglutination in
      Campylobacter jejuni.
AB  - Some bacteria can communicate with other species of bacteria by means of
      autoinducer-2 (AI-2)-mediated quorum sensing. In this study, we demonstrated that
      AI-2-mediated quorum sensing influences the transcription of flaA, the major
      flagellin gene in Campylobacter jejuni. A null mutation of luxS in C. jejuni
      strain 81116 reduced flaA transcription (approximately 43% that of the wild-type)
      and induced a reduction in motility. However, the luxS mutant had the same level
      of total flagellin protein as the wild-type. Transmission electron microscopy
      showed that the flagellar structure was preserved in the luxS mutant. The
      agglutination capability was reduced in the mutant strain, implying that quorum
      sensing might be involved in the formation of surface structures of C. jejuni.
      These observations suggest that AI-2-mediated quorum sensing may play a role in
      regulation of motility and surface properties in C. jejuni.

PMID- 14638995
TI  - Mycobacterial infection in MyD88-deficient mice.
AB  - MyD88 is an adaptor protein that plays a major role in TLR/IL-1 receptor family
      signaling. To understand the role of MyD88 in the development of murine
      tuberculosis in vivo, MyD88 knockout (KO) mice aerially were infected with
      Mycobacterium tuberculosis. Infected MyD88 mice were not highly susceptible to M.
      tuberculosis infection, but they developed granulomatous pulmonary lesions with
      neutrophil infiltration which were larger than those in wild-type (WT) mice (P <
      0.01). The pulmonary tissue levels of mRNA for iNOS and IL-18 were slightly
      lower, but levels of mRNA for IL-1 beta, IL-2, IL-4, IL-6, IL-10, IFN-gamma, and
      TGF-beta were higher in MyD88 KO mice. IFN-gamma, TNF-alpha, IL-1 beta, and IL-12
      also were high in the sera of MyD88 KO mice. There were no statistically
      significant differences in the expression of TNF-alpha, IL-12, and ICAM-1 mRNA
      between MyD88 KO and WT mice. Thus, MyD88 deficiency did not influence the
      development of murine tuberculosis. NF-kappa B activity was similar in the
      alveolar macrophages from the lung tissues of MyD88 KO and WT mice. Also, there
      may be a TLR2-specific, MyD88-independent IL-1 receptor/TLR-mediated pathway to
      activate NF-kappa B in the host defense against mycobacterial infection.

PMID- 14638996
TI  - A novel type of two-component regulatory system affecting gingipains in
      Porphyromonas gingivalis.
AB  - We surveyed the Porphyromonas gingivalis W83 genome database for homologues of
      FimS, the first two-component sensor histidine kinase, which could possibly
      control virulence factors. Including fimS, we found six putative sensor kinase
      genes in the genome. The gene encoding one of the homologues was cloned from a P.
      gingivalis plasmid library, sequenced, and analyzed using its mutants. Two gene
      disruption mutants were created in strain ATCC 33277 by introducing a drug
      cassette into the gene. The mutants formed nonpigmented colonies, indicating that
      they might be defective in proteinase production, a characteristic of this
      organism. Proteinase activities, measured as arginine- and lysine-specific (Rgp
      and Kgp gingipains, respectively) activities, of the mutants were almost half
      those of the parent strain. Unlike the parent and wildtype strains, most of the
      gingipain activities were detected in the culture supernatant, not in cells, of
      the mutants. Abnormal production of gingipains was confirmed by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and Western blot analyses. These
      results strongly suggest that this newly-discovered two-component sensor kinase
      is involved in maturation and proper localization of gingipains to the outer
      membrane through an unknown mechanism. The gene encoding the sensor histidine
      kinase was designated gppX, which represents regulation (X) of gingipains and
      black pigmentation in P. gingivalis.

PMID- 14638997
TI  - Use of the dnaJ gene for the detection and identification of all Legionella
      pneumophila serogroups and description of the primers used to detect 16S rDNA
      gene sequences of major members of the genus Legionella.
AB  - We sequenced about 930 bp of the dnaJ gene from 15 Legionella pneumophila
      serogroups and some other members of the genus Legionella. As L. pneumophila 16S
      rDNA sequences could not discriminate between all subspecies and serogroups, we
      assessed the use of dnaJ gene sequences to differentiate between Legionella
      subspecies as well as between L. pneumophila serogroups. A phylogenetic analysis
      revealed that dnaJ gene sequences were more variable between the L. pneumophila
      serogroups than mip gene and 16S rDNA sequences. By studying 61 strains from 41
      species of the genus Legionella, as well as other genera, we established a PCR
      method that could amplify 285 bp of dnaJ gene from all L. pneumophila serogroups.
      This primer set was more sensitive than mip gene primers and was able to detect
      0.25 ng of purified DNA. We also describe the 16S rDNA primers that were used to
      detect most Legionella genus members.

PMID- 14638998
TI  - Two different scrapie prions isolated in Japanese sheep flocks.
AB  - Two different scrapie prion strains with different characteristics were obtained
      from two sheep naturally infected with scrapie in Japan. In mice transmission,
      one (Tsukuba-1) showed shorter incubation periods (133+/-2 days) than the other
      (Tsukuba-2) (288+/-5 days). Spongiform changes and accumulation of an abnormal
      isoform of prion protein (PrP(Sc)) were observed throughout the brain in Tsukuba
      1 inoculated mice, while the lesions and the PrP(Sc) accumulation were localized
      in the brain stem of mice with Tsukuba-2. Western blot analysis showed that there
      was no strain-specific glycoform of PrP(Sc) within these two strains. A super
      infection experiment revealed that neither strain interfered with the other's
      propagation.

PMID- 14638999
TI  - Biofilm formation by a fimbriae-deficient mutant of Actinobacillus
      actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans strain 310-TR produces fimbriae and forms a
      tight biofilm in broth cultures, without turbid growth. The fimbriae-deficient
      mutant 310-DF, constructed in this study, was grown as a relatively fragile
      biofilm at the bottom of a culture vessel. Scanning electron microscopy revealed
      that on glass coverslips, 310-TR formed tight and spherical microcolonies, while
      310-DF produced looser ones. These findings suggest that fimbriae are not
      essential for the surface-adherent growth but are required for enhancing cell-to
      surface and cell-to-cell interactions to stabilize the biofilm. Treatment of the
      310-DF biofilm with either sodium metaperiodate or DNase resulted in significant
      desorption of cells from glass surfaces, indicating that both carbohydrate
      residues and DNA molecules present on the cell surface are also involved in the
      biofilm formation.

PMID- 14639000
TI  - TCR delta gene rearrangements revealed by fine structure of the recombination
      junction in mice.
AB  - The standard products of V(D)J recombination of immunoglobulin and T cell
      receptor genes are two kinds of DNA junction, a coding joint and a signal joint.
      TCR delta V-D and D-D signal joints in adult mouse thymocytes were sequenced
      following PCR amplification. We observed differential nucleotide insertions at
      the V delta-D delta signal joints, depending on the V delta and D delta gene
      usage in the developmental stage. Nucleotide insertions at the V delta-D delta 1
      signal joints were less frequent for the V delta 4, 5 genes preferentially
      utilized in adult thymocytes than for the V delta 3, 6 genes, infrequently
      rearranged to D delta 1. In addition to standard signal joints, unexpectedly,
      novel nonstandard products, "replacement joints" of D delta 1 substituted
      downstream by the recombination signal sequence of V delta were also found.
      However, no D delta 2-associated replacement joints other than V delta 5 were
      found. The other replacement joints of D delta 1-D delta 2 recombination were
      also observed. The mutation in TCR beta gene affected the frequency of nucleotide
      insertions at the V delta-D delta signal joints and inhibited the formation of
      replacement joint. Recombination mechanism generating the replacement joint and
      the possible role of TCR beta in up-regulation of TCR delta gene rearrangements
      are discussed.

PMID- 14639001
TI  - Tyrosine kinase as molecular target of anti-tumor drug.
AB  - Tyrosine kinase (TK) plays an important role in a variety of biological
      circumstances including growth, apoptosis, differentiation, immune system,
      angiogenesis, development, and so forth. Some inhibitors for TK have been
      successful in clinical applications in malignant disorders. Due to its
      physiological participation in cells exposed to many stimuli and to structural
      homology of high degree, true molecular targeting requires complete understanding
      of signal transduction pathways in all of the cells in which the targeted TK is
      involved.

PMID- 14639002
TI  - Tyrosine kinase inhibitor as a therapeutic drug for chronic myelogenous leukemia
      and gastrointestinal stromal tumor.
AB  - The Philadelphia chromosome found in leukemia cells of chronic myelogenous
      leukemia (CML) patients is produced by translocation between chromosomes 9 and
      22, resulting in expression of a chimera protein of Bcr and Abl kinase in the
      cytoplasm. Bcr-Abl kinase attracted oncology researchers as a molecular target
      for CML therapy, and a variety of small Abl kinase inhibitors were synthesized.
      STI571 (imatinib mesylate) was produced by modification of 2
      phenylaminopyrimidine, a core structure of protein kinase C inhibitor, to improve
      selectivity, stability, solubility, and bioavailability. STI571 competitively
      binds to the ATP binding site of Bcr-Abl kinase and inhibits Abl tyrosine kinase
      activity. STI571 showed significant efficacy in the clinical study with CML
      patients at all stages: chronic phase, accelerated phase, and blast crisis. More
      than 90% of the patients showed good hematologic response to STI571. STI571 is
      also a potent inhibitor of a receptor-type c-Kit tyrosine kinase. Therefore,
      STI571 was examined for therapeutic efficacy against malignant Gastro-Intestinal
      Stromal Tumors (GIST), which are mainly caused by aberrant expression of a
      mutated c-Kit that is constitutively active without binding of a ligand, stem
      cell factor (SCF). More than a half of the metastatic GIST patients enrolled in
      the clinical study responded to STI571. Thus, STI571 is now used as a therapeutic
      drug for both CML and GIST in more than 80 countries worldwide. Certain point
      mutations in the ATP binding site were found to be a cause of resistance to
      STI571 in both Bcr-Abl and c-Kit kinases. Therefore, it would be better to make a
      precise therapeutic strategy with STI571 based on the gene analysis data. It is
      also expected that it will be possible to design an inhibitor to overcome such
      resistance by using the structural information on the mutants.

PMID- 14639003
TI  - EGFR tyrosine kinase inhibitor "gefitinib (Iressa)" for cancer therapy.
AB  - Many malignant tumors including non-small cell lung cancer (NSCLC) express or
      over-express EGFR that have shown correlations with rapid growth, metastases,
      resistance to conventional chemotherapy or radiotherapy, and poor prognosis.
      Gefitinib is a potent and selective inhibitor of EGFR tyrosine kinase (EGFRTK).
      Gefitinib specifically inhibited EGF-stimulated cell proliferation in vitro and
      it also exhibited a broad anti-tumor spectrum against NSCLC, prostate,
      colorectal, and ovarian cancers in vivo. Gefitinib showed dose-dependent and
      reversible reduction of c-fos mRNA level and decreased Ki67 significantly in
      tumors in vivo. In in vitro studies, gefitinib arrested the cell cycle at G1
      phase by inducing intrinsic cyclin-dependent kinase (cdk) inhibitors and
      following inhibition of cdk2. Apoptosis was also seen in gefitinib-treated tumor
      cells and skin biopsy samples from clinical study. Gefitinib inhibited VEGF
      production in tumor cells through inhibition of EGFR signaling, leading to
      suppression of angiogenesis. In clinical studies, gefitinib demonstrated
      therapeutic benefit in patients who failed conventional chemotherapy. No
      correlation has been established between the anti-tumor activity of gefitinib and
      EGFR expression level, whilst sensitivity factors to gefitinib are yet to be
      elucidated. Identification of sensitivity factors will be a key for effective use
      of EGFRTK inhibitors including gefitinib for cancer treatment.

PMID- 14639004
TI  - VEGF-receptor inhibitors for anti-angiogenesis.
AB  - Angiogenesis is deeply involved in the progression of major diseases such as
      cancer, diabetes, and rheumatoid arthritis. Molecular mechanism on angiogenesis
      was extensively studied, and several signaling systems including VEGF (VEGF-A),
      angiopoietin, PDGF, and ephrin were shown to be crucial for physiological
      angiogenesis. Interestingly, among these factors, VEGF appears to play key roles
      in most of the pathological angiogenesis, and other factors are considered to
      have additional effects on its development depending on the situation. VEGF binds
      and activates two tyrosine kinase receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk
      1), and stimulates endothelial cell growth, survival, and vascular permeability.
      VEGF induces not only tumor angiogenesis but also blood-vessel-dependent
      metastasis. Based on the importance of VEGF in diseases, many companies and
      institutes are now trying to generate appropriate small molecules as well as
      proteins that strongly antagonize the VEGF-VEGFR system. Several molecules quite
      effective for suppression of tumorigenesis and pathological angiogenesis in
      animal models are under clinical trials.

PMID- 14639005
TI  - Development of HER2-specific humanized antibody Herceptin (trastuzumab).
AB  - HER2 is a member of the human epidermal growth factor receptor family, possessing
      protein kinase activity in its cytoplasmic domain. There were evidences
      indicating that (1) amplification of HER2/neu gene and HER2 protein over
      expression in tumor cells was observed in 25-30% of human breast cancer and (2)
      amplification of HER2/neu correlated with poor prognosis, including shorter
      disease-free and overall survival. These evidences suggested HER2 was a promising
      candidate for novel molecular targets of breast cancer therapy. Herceptin is a
      recombinant humanized monoclonal antibody generated by Genentech, Inc. for the
      treatment of HER2 over-expressed/HER2 gene amplified metastatic breast cancer
      (MBC). Preclinical studies demonstrated that the antibody had anti-tumor activity
      in vivo and in vitro, and additive or synergistic enhancement of anti-tumor
      activity of the antibody was observed in combination with various anti-tumor
      agents in mouse models. In clinical studies, apparent extension of overall
      survival was observed in HER2 overexpressing MBC patients. Herceptin is the first
      anticancer drug whose use as a treatment for MBC patients is decided based on the
      status of the HER2 gene amplification/HER2 protein over-expression. The
      development and standardization of HER2 test were a key strategy in clinical
      development of this drug, since appropriate selection of patients with HER2 over
      expression was the essential point for success.

PMID- 14639006
TI  - Recent advances in the study of AMPA receptors.
AB  - As glutamate is a dominant excitatory neurotransmitter in the central nervous
      system, glutamate receptors, and especially AMPA receptors, are located
      ubiquitously in all brain areas. In this paper, we reviewed recent advances of
      studies on AMPA receptor functions. AMPA receptors are cation-conducting
      complexes composed of various combinations of four subunits (GluR1 to GluR4). The
      glutamine residue located in the pore-forming segment of GluR2 subunit (Q/R site)
      is changed to arginine by RNA editing at the pre mRNA stage in normal adult
      mammalian animal. The edited GluR2 subunit is a major determination of Ca(2+)
      permeability of the AMPA receptor; only edited GluR2-lacking receptor shows high
      Ca(2+) permeability. The assembly of glutamate AMPA receptor subunit is not
      completely according to the stochastic theory. The heteromeric subunits assembly
      is more rapid than the homomeric assembly is. The transfer of AMPA receptor
      subunit to the plasma membrane is conducted in multiple ways. Many molecules that
      interact with the intracellular domain of AMPA receptor subunits are reported as
      the modulators of AMPA receptor subunit transfer. In the motoneuron of sporadic
      amyotrophic lateral sclerosis (ALS) patients, the efficiency of RNA editing at
      the GluR2 Q/R site is significantly decreased. Relative low level of edited GluR2
      subunit expression is likely responsible for motoneuronal death in ALS. Recently,
      AMPA receptors in glial cells have been studied. Bergmann glial cells in
      cerebellum express Ca(2+)-permeable AMPA receptors. Conversion of these AMPA
      receptors to Ca(2+)-impermeable type receptors induces morphological and
      functional changes. Glioblastoma cells also express Ca(2+)-permeable AMPA
      receptors, and their conversion to Ca(2+)-impermeable receptors inhibits cell
      locomotion and induces apoptosis.

PMID- 14639007
TI  - Pharmacological effects of ivermectin, an antiparasitic agent for intestinal
      strongyloidiasis: its mode of action and clinical efficacy.
AB  - Ivermectin is an oral semi-synthetic lactone anthelmintic agent derived from
      avermectins isolated from fermentation products of Streptomyces avermitilis.
      Ivermectin showed a concentration-dependent inhibitory effect on motility of a
      free-living nematode, Caenorhabditis elegans (C. elegans). There exist specific
      binding sites having a high affinity for ivermectin in the membrane fraction of
      C. elegans, and a strong positive correlation was detected between the affinity
      for these binding sites and the suppressive effect on motility of C. elegans in
      several ivermectin-related substances. These results suggested that the binding
      to these binding sites is important for the nematocidal activity of ivermectin.
      In oocytes of Xenopus laevis injected with the Poly (A)(+) RNA of C. elegans,
      expression of a chloride channel, which is irreversibly activated by ivermectin,
      was recognized. The pharmacological properties of this channel suggest that the
      ivermectin-sensitive channel is a glutamate-activated chloride channel. As to the
      glutamate-activated chloride channel, two subtypes (GluCl-alpha and GluCl-beta)
      were cloned, suggesting these subtypes constitute the glutamate-activated
      chloride channel. These findings suggest that ivermectin binds to glutamate
      activated chloride channels existing in nerve or muscle cells of nematode with a
      specific and high affinity, causing hyperpolarization of nerve or muscle cells by
      increasing permeability of chloride ion through the cell membrane, and as a
      result, the parasites are paralyzed to death. In experimental infections in sheep
      and cattle, ivermectin exhibited potent dose-dependent anthelmintic effects on
      Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Oesphagostomum, and
      Dictyocaulus. Anthelmintic effects were reported also in dogs, horses, and humans
      infected with Strongyloides. In the clinical Phase III trial in Japan, 50
      patients infected with Strongyloides stercoralis were administered approx. 200
      microg/kg of ivermectin to be given orally twice at an interval of 2 weeks. As a
      result, the Strongyloides stercoralis-eradicating rate was 98.0% (49/50).

PMID- 14639008
TI  - Pharmacological profiles and clinical effects of azelnidipine, a long-acting
      calcium channel blocker.
AB  - Azelnidipine (Calblock) is a newly developed dihydropyridine-type calcium
      antagonist for the treatment of hypertension. In hypertensive animals, a single
      oral administration of azelnidipine caused a slowly developed and long-lasting
      hypotensive effect with a little reflex tachycardia. The extent of tachycardia
      was less with azelnidipine than with other agents of the same class. Long-term
      administrations of azelnidipine produced a stable antihypertensive effect with a
      slight decrease in heart rate. The hypotensive effect was preceded by an increase
      in plasma drug concentration and it persisted even after plasma drug
      concentration declined to very low levels. In the isolated arteries, the calcium
      blocking action developed gradually after treatment with azelnidipine and
      survived for a long period of time after the drug was removed from the bathing
      solution. These data suggest that the high affinity to vascular tissue
      contributes to the long-lasting hypotensive effects of this agent. The results
      from clinical studies in hypertensive patients indicated that once daily
      administration of azelnidipine achieved stable, 24-h control of blood pressure
      with no change or a slight decrease in heart rate. Clinical studies also showed a
      low incidence of adverse events such as headache, facial flush, dizziness, and
      palpitations. These characteristics make azelnidipine a new generation calcium
      antagonist that can be used for the treatment of hypertension.

PMID- 14639009
TI  - Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral
      active derivative of fluoropyrimidine.
AB  - Xeloda (Capecitabine) is a fluorocytidine derivative that is selectively tumor
      activated to its cytotoxic moiety, fluorouracil. Capecitabine is readily absorbed
      from the gastrointestinal tract. In the liver, a 60-kDa carboxylesterase(CE)
      hydrolyzes much of the compound to 5'-deoxy-5-fluorocytidine (5'-DFCR). Cytidine
      deaminase(CD), an enzyme found in most tissues, including tumors, subsequently
      converts 5'-DFCR to 5'-deoxy-5-fluorouridine (5'-DFUR). The enzyme thymidine
      phosphorylase (TP) then hydrolyzes 5'-DFUR to the active drug 5-FU. It is proved
      that some human carcinomas express TP in higher concentrations than surrounding
      normal tissues. In Japan, one of the phase 2 clinical trials tested the efficacy
      of twice daily oral Capecitabine at 1,657 mg/m(2)/d given for 3 weeks followed by
      a 1-week rest period and repeated in 4-week cycles in advanced/metastatic breast
      cancer patients resistant to or recurring during or after docetaxel therapy. The
      response rate was 20.0% (1 CR, 10 PRs). The median time to progression was 84
      days and the median survival time was 452 days. The most common treatment-related
      adverse events throughout the phase 1 to 2 trials of capecitabine were hand-foot
      syndrome (50.7%), erythropenia (37.9%), lymphopenia (31.0%), hyperbilirubinemia
      (33.0%) and so on. Capecitabine is expected to provide a new alternative for the
      treatment of advanced/metastatic breast cancer.

PMID- 14639010
TI  - Sudden cardiac arrest and automated external defibrillators.

PMID- 14639011
TI  - Molecular strategies to treat vascular diseases: circulating vascular progenitor
      cell as a potential target for prophylactic treatment of atherosclerosis.
AB  - Atherosclerosis is responsible for more than half of all deaths in Western
      countries. Numerous studies have reported that accumulation of smooth muscle
      cells (SMCs) plays a principal role in atherogenesis, post-angioplasty restenosis
      and transplantation-associated vasculopathy. Although much effort has been
      devoted to targeting the migration and proliferation of medial SMCs, effective
      therapy to prevent occlusive vascular remodeling has not been established.
      Recently, it was suggested that bone marrow-derived precursors can give rise to
      vascular cells that contribute to the repair, remodeling, and lesion formation of
      the arterial wall under certain circumstances. This review highlights the recent
      findings on circulating vascular precursors and describes the potential
      therapeutic strategies for vascular diseases, targeting mobilization, homing,
      differentiation and proliferation of circulating progenitor cells.

PMID- 14639012
TI  - Arrhythmia and conduction disturbances in patients with congenital heart disease
      during pregnancy: multicenter study.
AB  - The incidence, manifestation and management of arrhythmia in congenital heart
      disease (CHD) during pregnancy were evaluated in a multicenter study. Of 126
      pregnancies in patients with CHD in 17 institutions from January 1991 to December
      2000, 29 cases of pregnancy in 27 patients after cardiac repair (mean age, 29+/
      4.9 years) were identified with arrhythmias (supraventricular tachyarrhythmia
      (SVT) in 15, ventricular tachycardia (VT) in 9, high-grade atrioventricular block
      in 4 and sick sinus syndrome in 3) (group A) and 29 control pregnancies from 29
      patients with repaired CHD and no arrhythmias (group B). SVT tended to require
      anti-arrhythmic medication more than VT (10/15 vs 2/9, p=0.04). Nine different
      types of anti-arrhythmic agents were successfully administered without maternal
      complications. There were no maternal deaths in either group. In the comparison
      of group A with group B, there was lower cardiac functional class (8/29, p=0.04),
      higher incidence of polysplenia (4/29, p=0.04), and higher incidence of low
      birthweight infant (7/29, p=0.02) in the former. It appears that there is a high
      prevalence of arrhythmias during pregnancy in patients with repaired CHD.
      Patients with CHD and low cardiac functional class and/or polysplenia could have
      arrhythmia during pregnancy that results in a low-birthweight infant. Meticulous
      care for these patients during pregnancy is recommended.

PMID- 14639013
TI  - Evaluation by contrast-enhanced electron beam computed tomography of myocardial
      perfusion and tissue characteristics in congenital aortic stenosis.
AB  - The evaluation of myocardial perfusion and tissue characteristics gives useful
      information regarding the indication for surgery. In the present study, two-phase
      contrast enhanced electron beam computed tomography (EBT) was used to
      quantitatively examine myocardial perfusion and the tissue characteristics of the
      left ventricular (LV) myocardium in congenital aortic stenosis (AS). The AS group
      comprised 15 patients and the control group had 14 non-AS patients. Myocardial
      ischemia and tissue characteristics were evaluated by the ratio of the
      incremental CT number of the myocardium (M) and the lumen (L) of the LV (M/L) in,
      the early phase with and without dipyridamole (Dp) loading and in the late phase
      after enhancement (respectively). In a comparison between the AS group and the
      controls, mean early M/Ls were significantly lower in the AS group than in the
      controls (20+/-5% vs 37+/-10%, p<0.01) and mean late M/Ls in the AS group were
      also significantly lower (47+/-11% vs 62+/-13%, p<0.01). In the AS patients,
      early M/Ls in the subendocardial and apical regions were especially lower than
      those of other segments, but the late M/Ls in these segments were inversely
      higher than those of other segments. These results suggest 2 things: (1) the
      existence of latent LV myocardial ischemia in AS patients, which is probably
      because of a hypertrophied LV wall, in turn caused by afterload, and (2) the
      presence of more myocardial ischemia and interstitial fibrosis in the
      subendocardial and apical regions of the AS heart. Using Dp loading for the AS
      patients increased the clarity of the contrast images. Contrast-enhanced EBT is
      useful for evaluating myocardial characteristics and perfusion in AS, and gives
      new insight into the LV wall characteristics in AS, as well as an indication for
      surgical correction of congenital AS.

PMID- 14639014
TI  - Carotid stenosis and peripheral artery disease in Japanese patients with coronary
      artery disease undergoing coronary artery bypass grafting.
AB  - The combination of a change in lifestyle toward Western habits and an aging
      society, has led to a steady increase in the incidence of atherosclerotic
      diseases in the Japanese population. Coronary artery disease (CAD), carotid
      stenosis (CS), and peripheral artery disease (PAD) are major manifestations of
      generalized atherosclerosis and increase the risk of cardiovascular events.
      However, the incidence of CS and PAD in Japanese patients with CAD is not well
      known, so the present study investigated this in 380 consecutive patients with
      CAD undergoing elective coronary aorta bypass grafting (CABG) at Kishiwada
      Tokushukai Hospital between October 1999 and October 2001. The coexistence of CS
      and PAD in all patients was preoperatively evaluated by duplex ultrasonography
      and the ankle - brachial index (ABI). The average age of the study population was
      66.09.1 years (range, 42-87). The number of male patients was 293 (77.1%). The
      incidence of CS was 13.7% and 15.3% for PAD. Multivariate logistic regression
      analysis demonstrated that no particular traditional atherosclerotic risk factor,
      such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, was able to
      predict either CS or PAD, but CS and PAD were independent predictors of each
      other. The results of the study suggest that CS and PAD were not only highly
      prevalent but also strongly associated with each other in this cohort of CAD
      patients. Accordingly, extracoronary atherosclerotic disease should be assessed
      in Japanese CAD patients.

PMID- 14639015
TI  - Who is at risk for cardiac events in young patients with long QT syndrome?
AB  - The objective of this study was to determine who is at risk for cardiac events
      among young patients with long QT syndrome (LQTS) with or without a past history
      of LQTS-related cardiac events. The subjects were young patients with LQTS who
      had visited one of 36 hospitals from January 1997 to August 2000 in Japan. To
      predict the risk factors for cardiac events, stepwise regression analyses were
      performed for a total of 197 cases. There were 7 of 129 cases (5%) without a past
      history and 32 of the 68 (47%) cases with a past history of LQTS-related cardiac
      events that experienced new events after diagnosis (p<0.0001). Patients with a
      family history showed a higher incidence of symptoms both before and after
      diagnosis than patients with sporadic occurrence. Analyses revealed that
      noncompliance with medication and a lower age at diagnosis were significant
      predictors for the group with a past history. A negative predictive value <4
      points was 100% in the group without a past history. To prevent future cardiac
      events, compliance with medication must be improved in those with a past history.
      A total LQTS score <4 points was useful to predict the absence of cardiac events
      in the group without a past history.

PMID- 14639016
TI  - Ultrasonic tissue characterization of the atherosclerotic carotid artery:
      histological correlates or carotid integrated backscatter.
AB  - Histological abnormalities of the atherosclerotic lesion are closely related to
      the stability of the plaque. Specifically, the plaque is likely to be unstable if
      the fibrous cap is thin. However, ultrasonic characterization of the
      atherosclerotic lesion has not been done from this viewpoint. Thus, in the
      present study ultrasonic tissue characterization of the carotid atherosclerotic
      lesion was attempted to assess the stability of the plaque. Integrated ultrasonic
      backscatter (IBS) in the atherosclerotic lesion was compared with histological
      findings of the respective tissue in 35 patients with carotid artery stenosis who
      underwent carotid endarterectomy. Carotid IBS was determined by locating the
      region-of-interest (ROI) in the center of the atherosclerotic lesion and
      calibrating by subtracting the IBS in the tunica externa of the vessel from the
      IBS of the ROI. IBS was also determined at the interface of the plaque, and at
      this site it was analyzed in relation to the thickness of the fibrous cap. Lipid
      content, fibrous tissue, thrombus, hemorrhage and calcification were
      histologically assessed in the respective tissue. Carotid IBS in the lipid lesion
      (-22.5+/-4.1 dB) was significantly different from that of fibrous, hemorrhagic or
      calcified lesions (-11.1+/-7.1, -27.5+/-4.1, +2.1+/-6.5 dB, respectively), but
      there was no significant difference in IBS between the lipid lesion and thrombus
      (-15.2+/-8.8 dB). IBS was lower in the thin fibrous cap than in the thick lesion
      (-10.9+/-6.4 vs -2.4+/-6.2 dB, p<0.001). IBS can be used to characterize
      atherosclerotic lesions in the carotid artery; a low value at the interface
      suggests a thin fibrous cap, which is frequently associated with unstable plaque.

PMID- 14639017
TI  - Correlation of connexin43 expression and late ventricular potentials in
      nonischemic dilated cardiomyopathy.
AB  - Nonischemic dilated cardiomyopathy (DCM) is associated with a high risk of sudden
      cardiac death. Signal-averaged electrocardiography (SAECG) is a useful clinical
      tool for detecting late ventricular potentials (LP). Gap junction alterations
      have recently been shown to be involved in the pathogenesis of ventricular
      arrhythmias in DCM; however, the possible relationship between gap junctional
      connexin43 (C x 43) expression and SAECG has not yet been evaluated. In the
      present study 16 patients (47+/-13 years) with DCM who had undergone SAECG
      testing were evaluated. In each patient, the expression of C x 43 proteins was
      qualitatively and quantitatively determined using immunoconfocal microscopy and
      right ventricular biopsy specimens. The level of expression of C x 43 protein was
      defined as the proportion of tissue area occupied by C x 43 (percent tissue area)
      in each test area. The abundance and distribution of the C x 43 signal was
      assessed in relation to LP. Late ventricular potentials were positive in 5
      patients (LP (+) group) and negative in 11 patients (LP (-) group). The incidence
      of sustained ventricular tachycardia in the LP (+) group was higher than that in
      the LP (-) group (80% vs 18%, p=0.04). The percent tissue area of C x 43 in the
      LP (+) group was significantly lower than that in the LP (-) group (p=0.02).
      Furthermore, C x 43 protein in the LP (+) group was distributed more
      heterogeneously than that in the LP (-) group (p=0.001). The heterogeneous
      expression of C x 43 protein may contribute to impaired ventricular conduction,
      which may be related to the LP detected on SAECG.

PMID- 14639018
TI  - Endothelin-1 and nitric oxide concentrations and their response to exercise in
      patients with slow coronary flow.
AB  - In this study, the endothelin-1 (ET-1) and nitric oxide (NO) concentrations in
      slow coronary flow (SCF) patients were assessed before and at the peak of the
      exercise stress test and compared with the values from healthy controls. The
      study population was 25 patients who underwent coronary angiography and were
      diagnosed as SCF (11 females (44%), aged 56.7+/-9.8 years), and 20 normal
      subjects (9 females (45%), aged 54.3+/-9.2 years). Mean TIMI frame count in the
      patients was 54.1+/-13.4. Blood samples were drawn at rest and immediately at the
      end of exercise testing. The baseline ET-1 concentrations of the control subjects
      were lower than those of the patients (7.0+/-4.5 pg/ml vs 11.1+/-5.9 pg/ml
      p<0.0001) and this difference increased after exercise (6.2+/-4.3 pg/ml vs 20.1
      +/-10.4 pg/ml, p<0.0001). Post-exercise ET-1 concentrations were significantly
      higher than baseline in patients with SCF (p<0.0001) and a reduction in the ET-1
      concentrations was observed in control subjects (p<0.05). Baseline NO
      concentrations of the patients were lower than those of the control subjects (27
      +/-5.1 micromol/L vs 31.2+/-4.9 micromol/L, p=0.0001). Although the NO
      concentrations in both groups were significantly increased after exercise (29.4
      +/-5.9 micromol/L vs 33.3+/-5.6 micromol/L, p<0.05 for both), the difference was
      not significant. A significant negative correlation among post-exercise ET-1
      concentrations and maximal heart rate, exercise duration and exercise rate -
      pressure product, and a significant positive correlation among post-exercise NO
      concentrations and maximal heart rate and exercise duration were observed in both
      groups. The results of this study show that endothelial function (assessed by ET
      1 and NO concentrations) and its response to exercise were abnormal in SCF
      patients compared with healthy subjects, and this may play some pathophysiologic
      role.

PMID- 14639019
TI  - Lesion severity and hypercholesterolemia determine long-term prognosis of
      vasospastic angina treated with calcium channel antagonists.
AB  - Although patients with medically treated vasospastic angina have a good outcome,
      few data exist regarding the role of underlying lesion severity associated with
      or without hyperlipidemia in the prognosis. Therefore, the aim of the present
      study was to assess the relationship between the long-term outcome of vasospastic
      angina and the factors influencing its prognosis. A total of 256 patients (219
      men, 37 women; mean age, 54.1+/-9.2) who had coronary spasm with or without
      underlying lesions and were being treated with calcium channel antagonists were
      enrolled and followed for 13.6+/-3.7 years. Cardiac events consisted of cardiac
      death and ischemic events, which included acute myocardial infarction and
      unstable angina. Cox analysis selected coronary artery stenosis (CAS, >/=50%) and
      risk factors such as age, hypertension, diabetes mellitus, low-density
      lipoprotein-cholesterol (LDL-C), sex and smoking. There were 19 cases of cardiac
      death (7.4%) and 58 of ischemic events (22.7%) during the follow-up period. The
      presence of significant CAS was an independent predictor of event-free survival
      (hazard ratio (HR) =2.84, 95% confidence interval (CI) =1.79-4.52, p<0.0001). In
      193 patients without significant CAS, there were 10 cases of cardiac death (5.2%,
      p<0.05) and 34 of ischemic events (17.6%, p<0.01). In that group, high LDL-C was
      the independent predictor of event-free survival (HR = 3.89, 95% CI = 1.20-12.6,
      p=0.02). Kaplan-Meier survival analysis revealed significantly lower event-free
      survival in patients with than in those without lesions (p<0.0001 by log-rank
      test). These results demonstrate that the most important factor for long-term
      prognosis of vasospastic angina treated with calcium channel antagonists is
      significant CAS. High LDL-C, which might alter the underlying coronary
      endothelial function and/or accelerate atherosclerotic lesions, could also
      contribute to the occurrence of cardiac events, particularly in patients without
      significant CAS.

PMID- 14639020
TI  - Improvement of the diagnostic accuracy in computer-assisted differential
      diagnosis for wide QRS premature complexes.
AB  - The differential diagnosis of wide QRS premature contractions is often inaccurate
      in most ECG machines with automatic computer-assisted diagnosis. The purpose of
      the present study was to improve the accuracy of the automated differential
      diagnosis between premature ventricular contractions (PVC) and supraventricular
      contractions with aberrant conduction (A-PSC). The study investigated 180
      consecutive electrocardiograms (ECGs) with wide QRS premature contractions picked
      up from 3,723 in the ECG database. A new algorithm, Detection of Wide QRS Complex
      --> Second Derivative --> Absolute Value --> Smoothing --> T Wave Subtraction -->
      P' Detection, was compared with a conventional QRS morphology algorithm and P'
      algorithm without T wave subtraction. The rate of false positives was reduced
      step by step (22.3% in the conventional algorithm, 7.8% in the P' without T
      subtraction algorithm and 3.0% in the P' with T subtraction algorithm), resulting
      in a marked increase in diagnostic accuracy for A-PSC from 77.2% to 90.6% and
      95.0%, respectively. In a general population with external samples, the newest
      algorithm showed 77.8% sensitivity, 99% specificity, and 98.9% accuracy for
      diagnosis of A-PSC. The new algorithm for differential diagnosis of wide QRS
      complexes is simple, reliable, and easy to apply to most 12-lead ECG machines
      with computer-assisted automatic diagnosis.

PMID- 14639021
TI  - Plaque morphology at coronary sites with focal spasm in variant angina: study
      using intravascular ultrasound.
AB  - In the present study, the intravascular ultrasound (IVUS) morphologic appearance
      of coronary atherosclerotic plaque associated with focal spasm was prospectively
      studied in 45 patients with or without focal coronary spasm provoked by
      ergonovine or acetylcholine. The percent plaque area and plaque arc were
      determined from the IVUS images at the sites of spasm. Calcified lesion was
      defined as the presence of high-intensity echo with acoustic shadowing. Twenty
      three patients had focal coronary spasm defined as angiographic narrowing >75%
      and IVUS demonstrated atherosclerotic plaque in these 23 sites. In the 22
      patients without focal spasm, IVUS demonstrated 18 atherosclerotic lesions in 17
      patients and the remaining 5 patients did not have significant lesions. There was
      no difference in the percent plaque area and plaque arc between plaque lesions
      with (47+/-10%, 298+/-71 degrees ) and without (39+/-15%, 249+/-83 degrees )
      coronary spasm. Interestingly, calcified lesion was less frequently present at
      the sites with than at those without spasm (p<0.05). These results indicate that
      the presence of plaque without calcification is likely to be related to the
      occurrence of focal vasospasm, although the severity and distribution of the
      disease did not differ between each patient group.

PMID- 14639022
TI  - A novel antioxidant, EPC-K1, stimulates endothelial nitric oxide production and
      scavenges hydroxyl radicals.
AB  - EPC-K1, a hydroxyl radical scavenger synthesized by phosphate linkage of vitamin
      E and vitamin C, prevents myocardial reperfusion injury in vivo; however, the
      direct effects of EPC-K1 on coronary arteries are unknown. These experiments were
      undertaken to define possible mechanisms through which EPC-K1 imparts its
      protective action on the coronary vasculature. EPC-K1 (10(-5) to 10(-1) mg/ml)
      induced concentration-dependent relaxation in contracted canine coronary artery
      segments with endothelium, but no change in tension of arterial segments without
      endothelium (p<0.05, ANOVA). Endothelium-dependent relaxation to EPC-K1 was
      inhibited by N(G)-monomethyl-(L)-arginine ((L)-NMMA) (10(-5) mol/L). Inhibition
      of relaxation by (L)-NMMA was reversed by the addition of (L)-arginine (10(-4)
      mol/L), but not by (D)-arginine (10 (-4) mol/L). Subsequent exposure of canine
      coronary artery segments with intact endothelium to hydroxyl radicals for 30 min
      (generated by FeSO(4) [0.56 mmol/L] + H(2)O(2) [0.56 mmol/L]) impaired
      endothelium-dependent relaxation. However, pretreating the vascular segments with
      EPC-K1 (10(-4) mg/ml) prevented hydroxyl radical-mediated endothelial cell injury
      and maintained endothelium-dependent relaxation. These experiments indicate that
      EPC-K1 stimulates the release of endothelium-derived nitric oxide, an endogenous
      vasodilator and inhibitor of platelet and leukocyte activation and adhesion, from
      the coronary artery endothelium. Additionally, EPC-K1 scavenges hydroxyl radicals
      that mediate endothelial cell injury. These 2 independent and important actions
      are possible mechanisms by which EPC-K1 prevents reperfusion injury in the
      ischemic heart.

PMID- 14639023
TI  - Effectiveness of angiotensin-converting enzyme inhibitor or angiotensin II
      receptor blocker on atrial natriuretic peptide.
AB  - The aim of this study was to evaluate the effectiveness of an angiotensin
      converting enzyne inhibitor (ACEI, quinapril) or angiotensin II receptor blocker
      (ARB, candesartan) on atrial natriuretic peptide (ANP) activity in rats with
      hypertension induced by nitric oxide (NO) inhibition. ACEI and ARB have a number
      of pharmacologic effects, including blood pressure reduction, myocardial
      preservation, and an unknown effect in the circulation. The changes in ANP in NO
      inhibitor-induced hypertensive rats were evaluated in order to elucidate the
      interaction between ANP and NO in the regulation of blood pressure. Thirty-six
      rats were divided into 4 groups and administered the experimental agents for 8
      weeks: group CONTROL was given regular food (n=9), group N(G)-nitro-L-arginine (L
      NNA) was administered L-NNA (25 mg. kg(-1). day(-1), n=9), group ACEI was
      administered L-NNA and quinapril (10 mg. kg(-1). day(-1), n=9), and group ARB was
      administered L-NNA and candesartan (10 mg. kg(-1). day(-1), n=9). Blood pressure,
      plasma ANP, atrial ANP, ANP mRNA, and ANP granules were measured. A significant
      elevation in blood pressure was observed in group L-NNA. However, there were no
      increases in plasma ANP (L-NNA: 138.8+/-64.4, CONTROL: 86.7+/-36.4), ANP mRNA (L
      NNA: 2.2+/-1.0, CONTROL: 1.7+/-0.5) or ANP granules (L-NNA: 61.1+/-10.2, CONTROL:
      64.5+/-8.5). No increase in blood pressure was seen in groups ACEI and ARB.
      However, plasma ANP (ACEI: 1,392.3+/-1,034.4, ARB: 1,142.8+/-667.3), ANP mRNA
      (ACEI: 52.8+/-29.1, ARB: 42.9+/-21.2), and ANP granules (ACEI: 122.5+/-23.4, ARB:
      136.3+/-33.2) increased significantly. NO inhibitor-induced hypertension caused
      no changes in ANP concentrations. However, the ACEI and ARB had a direct effect
      on the induction of ANP secretion. The findings suggest that ANP secretion is
      directly effected by ACEI and ARB, which seems to play a key role in lowering
      blood pressure, relieving heart failure symptoms, and preserving the myocardium.

PMID- 14639024
TI  - Transcatheter coil embolization of a high-flow coronary artery fistula using
      0.052-inch gianturco coils: a case report.
AB  - A giant, high-flow coronary fistula is usually difficult to treat by
      transcatheter coil embolization, but the 0.052-inch Gianturco coil, which is
      larger and has a stronger shape memory than conventional coils, is now available.
      Using this device and additional conventional coils, a high-flow coronary artery
      fistula in a healthy 31-year-old man was successfully embolized. The new
      Gianturco coil widens the indication for the transcatheter embolization of
      coronary artery fistulas.

PMID- 14639025
TI  - Percutaneous cardiopulmonary support aids resuscitation from sustained
      ventricular tachycardia.
AB  - A 67-year-old man was transferred to hospital because of acute circulatory
      failure resulting from sustained left ventricular tachycardia (LVT) and
      dysfunction. Transthoracic echocardiography revealed severely impaired left
      ventricular contraction and dyskinesis of the apical wall. Neither anti
      arrhythmic agents nor direct current cardioversion was effective; the patient was
      resuscitated by immediate use of percutaneous cardiopulmonary support and
      intraaortic balloon counterpulsation. Ventricular contraction returned to normal
      following restoration of normal sinus rhythm with amiodarone and cibenzoline. The
      pathogenesis of LVT accompanied by transient ventricular dyskinesis is discussed
      with regard to the efficient use of a mechanical circulatory support system in
      resuscitation.

PMID- 14639026
TI  - Endoluminal perspective volume rendering of coronary arteries using electron-beam
      computed tomography.
AB  - Remarkable progress has been made in the treatment of coronary heart diseases
      because of a variety of new interventional devices, but as each new device or
      procedure has suitability for a particular type of patient or purpose, patient
      selection is increasingly important. Endoluminal perspective volume renderings of
      the coronary arteries of a 70-year-old male with old myocardial infarction and
      recurrent chest pain were carried out using electron-beam computed tomography.
      Conventional coronary angiography had revealed significant stenosis of the distal
      portion of the left anterior descending branch, and subsequent conventional
      balloon angioplasty had failed to expand the stenotic site. Perspective volume
      rendering images can distinguish differences in objects and evaluate the cross
      sectional area of the lumen and the morphology of calcification. In the present
      patient, a huge mass of calcified plaque occupied most of the lumen at a site
      corresponding to the angiographic site of stenosis. According to this finding,
      rotational atherectomy was indicated and had a good outcome. The qualitative
      information for characterizing and determining the morphology of atherosclerotic
      plaque provided by perspective volume rendering may be useful in selecting the
      appropriate intervention.

PMID- 14639027
TI  - Unusual growth of a left atrial myxoma complicated by a secundum atrial septal
      defect.
AB  - A 55 year-old man had a myxoma that originated in the left atrium and grew
      through a secundum atrial septal defect into the right atrium. The tumor, which
      was attached by a pedicle to the lateral wall of the left atrium near the right
      pulmonary vein, was resected under cardiopulmonary bypass. Transesophageal
      echocardiography was important in the successful outcome of surgical treatment.

PMID- 14639028
TI  - A case of Melkersson-Rosenthal syndrome with features suggesting immune etiology.

PMID- 14639029
TI  - Lyme neuroborreliosis mimicking primary CNS lymphoma.

PMID- 14639030
TI  - Bilateral hypoglossal nerve involvement in chronic inflammatory demyelinating
      polyneuropathy.

PMID- 14639031
TI  - Chorea after cardiopulmonary bypass.

PMID- 14639032
TI  - Weight reduction due to stroke-induced dysgeusia.

PMID- 14639033
TI  - Neuroborreliosis with vasculitis causing stroke-like manifestations.

PMID- 14639034
TI  - Acute myocardial infarction following intravenous immunoglobulin therapy for
      chronic inflammatory demyelinating polyneuropathy in association with a
      monoclonal immunoglobulin G paraprotein.

PMID- 14639035
TI  - A rare homozygous missense mutation in ATP7B exon 19 in a case of Wilson disease.

PMID- 14639036
TI  - Diffusion-weighted imaging in Wernicke encephalopathy associated with stomach
      cancer: case report and review of the literature.

PMID- 14639037
TI  - Ileocecal valve-preserving ileostomy after total proctocolectomy--a novel
      technique for ileostomy.
AB  - BACKGROUND: Although ileoanal anastomosis has become popular for ulcerative
      colitis, in an emergency situation patients must undergo ileostomy. AIM: A novel
      ileocecal valve-preserving ileostomy procedure was devised to reduce high output
      liquid loss. METHOD: After total colectomy, the ascending colon was clamped and
      the terminal ileum and ileocecal valve were isolated from the cecum by
      dissection. The ileum was then brought out through a conventional ileostomy
      opening in the abdominal wall. RESULTS: Two patients with ulcerative colitis
      underwent ileostomy in this fashion. The stool became solid within 1 week after
      the start of solid food and their body weight increased by more than 10% 1 year
      after surgery. CONCLUSION: This novel procedure may result in an improvement in
      the quality of life of patients who undergo total proctocolectomy.

PMID- 14639038
TI  - Triple colon cancer successfully demonstrated by CT air-contrast enema.

PMID- 14639039
TI  - Erytropoietin concentrations in cerebrospinal fluid of nonhuman primates and
      fetal sheep following high-dose recombinant erythropoietin.
AB  - Erythropoietin (Epo) decreases neuronal injury and cell death in vitro and in
      vivo. To lay the groundwork for use of Epo as a potential therapy for brain
      injury, we tested the hypothesis that systemic dosing of high-dose recombinant
      Epo (rEpo) would result in neuroprotective rEpo concentrations in the spinal
      fluid of adult and developing animals. This report characterizes the
      pharmacokinetics of high-dose rEpo in the blood and spinal fluid of juvenile and
      adult nonhuman primates (n = 7) and fetal sheep (n = 37) following a single
      injection. Timed blood and spinal fluid samples were collected following rEpo
      injection. Epo accumulation in spinal fluid was dependent on peak serum
      concentration and time following injection. We demonstrate that high-dose rEpo
      was well tolerated and results in neuroprotective concentrations in spinal fluid
      of adult and developing animal models by 2-2.5 h after injection.

PMID- 14639040
TI  - Obesity indices and major components of metabolic syndrome in young adult Arab
      subjects.
AB  - BACKGROUND: The major components of metabolic syndrome are atherogenic
      dyslipidaemia (AD) and insulin resistance (IR), and both predict risk for
      atherosclerotic cardiovascular disease even in healthy individuals. AIMS: To
      assess if, in a group of healthy young adult Arab subjects, a simple
      classification in high and normal scores on waist-hip ratio (WHR), body mass
      index (BMI) and waist circumference (WC) scales could predict atherogenic
      parameters for metabolic syndrome (AD, IR). SUBJECTS AND METHODS: The subjects [n
      = 177 (72 M, 105 F), aged 29.7 +/- 8.4 (SD) years], underwent physical
      evaluation, BP measurement and anthropometry [height (m), weight (kg), waist (WC)
      and hip circumference (HC, cm)]. The cut-off points for normal/high scores on the
      indices were: (1) BMI: 30 kg/m(2) (M and F); (2) WHR: 0.80 F, 0.95 M, and (3) WC:
      90 cm F, 100 cm M). The biochemical indices measured on fasting serum were: (1)
      AD: total cholesterol (TC), triglycerides (TG), HDL, LDL, apo B, HDL/TC ratio,
      and (2) IR: insulin, urate, insulin/glucose ratio (IGR). RESULTS AND DISCUSSION:
      In the whole group of subjects, and in women separately considered, those with
      high indices (BMI, WHR, WC) had significantly increased levels of glucose, LDL,
      apo B, urate, mean BP, TG, insulin and IGR and lower values for HDL/TC ratio (all
      p < 0.05). In men, only urate, insulin and IGR levels were increased (p < 0.01)
      in the high-score groups. None of the indices showed any special superiority in
      describing the risk of AD or IR. CONCLUSION: In women, BMI, WHR and WC appeared
      equally good in identifying individuals at high risk of AD and IR while in men,
      these indices satisfactorily described the risk of IR but not of AD. It is
      important to re-emphasise the need to indicate gender distinctions in using
      anthropometry for CHD risk assessment.

PMID- 14639041
TI  - Comparative effects of the addition of meat from beef, chicken, mullet and hake
      to a bean seed ragout on iron metabolism and iron status in growing rats.
AB  - AIMS: The objective was to study the comparative effects of the addition of meat
      from beef, chicken, mullet and hake to a bean seed ragout (BSR) on iron
      metabolism and iron status in growing rats. METHODS: The iron metabolism and the
      iron status were investigated through the exploration of the total iron in the
      blood and the reserve of iron stored in the liver, spleen, intestine, heart and
      tibia. RESULTS: Our findings showed that the iron concentration in total blood
      significantly increased only in the BSR + beef group by 23% (p < 0.006) as
      compared to the control group (BSR). However, it significantly decreased in the
      BSR + chicken group by 19.3% (p < 0.002). The reserve of iron stored in the liver
      significantly increased in the BSR + beef and the BSR + hake groups by 69.5% (p <
      0.003) and 160% (p < 2.5.10(-7)) respectively, as compared to the control group.
      The effect of hake was more pronounced than beef. However, in the BSR + chicken
      and the BSR + mullet groups, the reserve of iron stored in the liver did not
      significantly differ from the control group. The reserve of iron stored in the
      spleen increased significantly in all groups. The increase has reached 370% in
      the BSR + hake group (p < 1.10(-7)). In the intestine, the reserve of iron was
      significantly enhanced only in the group fed BSR + beef by 120% (p < 0.01). In
      contrast, this reserve was lower in the rats fed BSR + mullet than in the other
      groups, a reduction of 64% (p < 1.10(-5)) as compared to the control group. In
      the heart, iron concentration significantly increased between 36.5 and 50%, as
      compared to the control group. The iron stored in the tibia significantly
      increased only in the beef and the hake groups by 88% (p < 0.05) and 57.4% (p <
      0.02) respectively. CONCLUSIONS: Our findings demonstrated that beef, chicken,
      mullet and hake did not have the same effect on iron metabolism and iron status
      in growing rats fed BSR diets. The rats fed BSR + beef have a better iron status
      than those fed BSR + hake, BSR + chicken or BSR + mullet in descending order.

PMID- 14639042
TI  - Influence of dietary triacylglycerol structure and level of n-3 fatty acids
      administered during development on brain phospholipids and memory and learning
      ability of rats.
AB  - OBJECTIVE: The objective of this study was to examine the effects of
      triacylglycerol (TAG) structure and level of n-3 fatty acids on fatty acid
      profile of brain phospholipids (PL) of dams and offspring, and the memory and
      learning ability of the offspring, when administered during initial development
      of the nervous system. METHODS: Pregnant rats were fed experimental diets from
      the 8th day of pregnancy throughout lactation. After weaning and until 13 weeks
      of age, the pups were fed the same diet as their dams. The experimental diets
      contained either a structured oil, a linseed oil, or a fish oil. In the
      structured oil, alpha-linolenic acid (18:3n-3) was predominantly located in the
      SN-2 position of the triacylglycerols and the level of 18:3n-3 was 2 mol or 10
      mol%. In the linseed oil diets the level of 18:3n-3 was 2 mol or 10 mol% as well.
      Finally, the fish oil diet contained 18:3n-3 as well as 20:5n-3 and 22:6n-3
      adding up to a total of 2 mol% n-3 fatty acids. The effects of the experimental
      diets were compared to the effect of a chow diet. RESULTS: The amount of 22:6n-3
      in brain phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) of dams and
      offspring (3 and 13 weeks of age) was not affected by the six different diets.
      18:2n-6, but not 18:3n-3, was detected in brain PL, suggesting a specificity of
      the tissues in the metabolism of n-3 and n-6 fatty acids. The level of
      monounsaturated fatty acids (MUFA) increased with increasing age of the pups,
      indicating an enhanced myelinization. No considerable differences between groups
      were found when memory or learning was tested in the Morris water maze.
      CONCLUSION: The results suggest that extreme diet modifications are needed in
      order to observe significant effects on the memory and learning ability in rats.

PMID- 14639043
TI  - Supplementation of female rats with alpha-linolenic acid or docosahexaenoic acid
      leads to the same omega-6/omega-3 LC-PUFA accretion in mother tissues and in
      fetal and newborn brains.
AB  - BACKGROUND: Maternal omega-3 fatty acid supplementation has been suggested to
      provide docosahexaenoic acid (DHA) for the normal brain development during
      gestation. DHA can be given as such (preformed) or through the omega-3 precursor
      alpha-linolenic acid (LNA) which is transformed into DHA by elongation and
      desaturation reactions. Western diet provides low amounts of LNA and DHA;
      therefore, supplementation with these omega-3 fatty acids has been suggested for
      pregnant women. However, the bioequivalence of LNA ingestion to DHA
      supplementation has not been established. METHODS: Recently weaning female Wistar
      rats were fed a diet containing a small amount of LNA and no DHA. The animals
      were daily supplemented 40 days before mating, during pregnancy, and until
      delivery with 60 mg/kg of LNA or 6 mg/kg of DHA dissolved in coconut oil. Fatty
      acids were given as ethyl ester derivatives. Controls received coconut oil. The
      fatty acid composition of blood plasma, erythrocytes, liver, visceral adipose
      tissue, and brain segments (frontal cortex, hippocampus, and cerebellum) was
      analyzed. Brain segments obtained from 16- and 19-day-old fetuses and from 2- and
      21-day-old rats were also analyzed for fatty acid composition. RESULTS:
      Supplementation with LNA and DHA induced a similar accretion of DHA in plasma,
      erythrocytes, liver, and brain segments of the mothers. The adipose tissue showed
      a higher DHA accretion after DHA-supplementation. The DHA accretion in frontal
      cortex, hippocampus, and cerebellum obtained from the fetuses and the newborn
      rats was similar when the mothers were supplemented with LNA and DHA. Our results
      show that under our experimental conditions a similar accretion of DHA in the
      different tissues of the mothers and in the brain segments of fetuses and newborn
      rats is obtained after LNA and DHA supplementation. CONCLUSION: LNA and DHA, at
      the amounts given in this study, show a similar bioequivalence for DHA accretion
      in different tissues of the mother and in brain segments of fetuses and newborn
      rats.

PMID- 14639044
TI  - Smoking and high plasma triglyceride levels as risk factors for oxidative DNA
      damage in the Korean population.
AB  - AIMS: To investigate the effects of factors including dietary habits, lifestyle,
      anthropometric characteristics, plasma lipid profiles, and antioxidants on DNA
      damage among the Korean population. METHODS: Blood samples were collected from
      109 healthy Korean volunteers, aged 19-28 years, of whom 34% were smokers.
      Epidemiological information was collected by personal interviews, and
      anthropometric characteristics were measured directly. Oxidative DNA damage was
      quantified using the Comet assay; tail length (TL) and tail moment (TM) were
      measured. RESULTS: Statistically significant (p < 0.05) positive correlations
      were observed between DNA damage (TM or TL) and smoking habits expressed as
      cigarettes smoked per day and number of packs smoked over time (r = 0.332 and
      0.370, respectively, for TM; r = 0.266 and 0.304 for TL, respectively). There
      were also significant and positive correlations between DNA damage parameters and
      waist-hip ratio (r = 0.352 for TM and r = 0.226 for TL), but this significance
      disappeared after data were adjusted to account for smoking effects. Higher
      plasma triglyceride levels were associated with increased damage to DNA (r =
      0.234 for TM and r = 0.271 for TL). CONCLUSIONS: Our results indicate that
      cigarette smoking and high plasma triglyceride levels significantly increase DNA
      damage to peripheral lymphocytes in a sample of Koreans.

PMID- 14639045
TI  - Lack of functional promoter polymorphisms in genes involved in glutamate
      neurotransmission.
AB  - OBJECTIVES: The regulation of genes involved in glutamatergic function is thought
      to be a critical for many central nervous system processes including memory,
      learning, synaptic maintenance, and many pathological states. As part of a larger
      survey into the key regulatory elements in genes of neuro-psychiatric interest,
      we sought to identify the promoter regions of genes in this broad family, and to
      identify sequence variants that alter gene expression. METHODS: Mutation analysis
      was carried out on the promoters of 20 genes encoding 13 glutamate receptor
      subunits, four transporters and three metabolizing enzymes using denaturing high
      performance liquid chromatography. Thirty-nine different promoter haplotypes were
      cloned into a luciferase reporter gene vector and tested for differences in their
      ability to drive transcription in both HEK293t and TE671 cell lines. RESULTS: We
      have identified a total of 48 sequence variants in six glutamate receptor
      subunits, four glutamate transporters and two enzymes. Interestingly, seven
      promoter sequences gave three or more haplotypes from a single individual,
      indicating gene duplication. No differences in expression greater than 1.35-fold
      were found between haplotypes originating from the same or paralogous genes.
      CONCLUSION: The lack of common functional polymorphisms in any of these promoters
      indicates that expression of glutamate receptors and transporters is unusually
      tightly controlled, and suggests the possibility that non-coding polymorphisms in
      these genes are rare and may be unlikely to contribute in a major way to neuro
      psychiatric phenotypes. This study represents the world's largest survey of the
      any group of promoters yet performed for any gene system.

PMID- 14639046
TI  - The nitric oxide synthase-3 codon 298 polymorphism is not associated with late
      onset sporadic Alzheimer's dementia and Lewy body disease in a sample from
      Hungary.
AB  - An association study was performed between apolipoprotein E (apoE) polymorphism
      and the common structural polymorphism Glu/Asp at codon 298 of the nitric oxide
      synthase (NOS3) gene in late-onset sporadic Alzheimer's dementia probands (LOAD),
      diffuse Lewy body dementia cases (DLBD) and controls in a Hungarian sample. The
      frequency of individuals who carried the apoE epsilon4 allele was significantly
      more common in both dementia groups (LOAD, 20%; DLBD, 27%; control, 8%; control
      versus DLBD, chi2=13.264, degrees of freedom=2, P<0.001; control versus LOAD,
      chi2=6.628, degrees of freedom=2, P<0.036). However, there were no significant
      differences in the NOS3 genotype and allele distributions between the LOAD, DLBD
      and control groups. The apoE status has been found to be independent from the
      NOS3 codon 298 polymorphism in the examined cohort. Despite the facts that NOS3
      is associated with neuritic sprouting, and aberrant neuronal and glial expression
      of the same molecule has been found in neurodegenerative diseases, it is unlikely
      that the polymorphism Glu/Asp of the NOS3 gene is involved in the development of
      LOAD and DLBD.

PMID- 14639047
TI  - A possible association between an insertion/deletion polymorphism of the NQO2
      gene and schizophrenia.
AB  - OBJECTIVE: Glutathione-S-transferases, NAD(P)H: quinone oxidoreductase1 (NQO1)
      and NRH: quinone oxidoreductase2 (NQO2) provide important cellular defences
      against the neurotoxicity induced by catecholamine-derived o-quinones and
      oxidative stress during redox cycling. In this study, we investigated the
      association between polymorphisms of the NQO2 gene and schizophrenia. METHODS: We
      analysed the promoter and coding regions of the NQO2 gene for 102 patients with
      schizophrenia and for 234 controls using single-strand conformational change
      polymorphism and PCR direct-sequencing analyses and the RNA concentration of NQO2
      in white blood cells isolated from peripheral blood was measured. RESULTS: We
      identified 12 variants including the insertion/deletion (I/D) polymorphism of the
      29 base pair nucleotide sequence in the promoter region. The frequency of the D
      allele was significantly higher in the schizophrenic group than in the control
      group (P=0.0109). Especially, in patients with the episodic type as course
      specifiers, this value was highly significant (P=0.0016) and the significance
      remained after the Bonferroni correction. The 29 base pair nucleotide sequence
      contains four repeats of the putative core sequence of the Sp1-binding cis
      element that is important in the activation of gene expression. Our preliminary
      data, although sample size was not enough, demonstrated that the RNA
      concentration of NQO2 in white blood cells isolated from peripheral blood was
      higher in individuals homozygous (II) for the I allele than in those heterozygous
      (ID) or homozygous (DD) for the D allele. CONCLUSION: The present data suggest
      that individuals with the deletion of the 29 base pair sequence in the promoter
      region of the NQO2 gene may confer susceptibility to a certain form of
      schizophrenia.

PMID- 14639048
TI  - Genetic association between the phospholipase A2 gene and unipolar affective
      disorder: a multicentre case-control study.
AB  - The co-segregation in one pedigree of bipolar affective disorder with Darier's
      disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and
      association studies with the neighbouring gene of phospholipase A2 (PLA2)
      indicate that PLA2 may be considered as a candidate gene for affective disorders.
      All relevant genetic association studies, however, were conducted on bipolar
      patients. In the present study, the possible association between the PLA2 gene
      and unipolar affective disorder was examined on 321 unipolar patients and 604
      controls (all personally interviewed), recruited from six countries (Belgium,
      Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European
      Collaborative Project on Affective Disorders. After controlling for population
      group and gender, one of the eight alleles of the investigated marker (allele 7)
      was found to be more frequent among unipolar patients with more than three major
      depressive episodes than among controls (P<0.01); genotypic association was also
      observed, under the dominant model of genetic transmission (P<0.02). In addition,
      presence of allele 7 was correlated with a higher frequency of depressive
      episodes (P<0.02). These findings suggest that structural variations at the PLA2
      gene or the chromosomal region around it may confer susceptibility for unipolar
      affective disorder.

PMID- 14639049
TI  - Mutation screening and association study of the UBE2H gene on chromosome 7q32 in
      autistic disorder.
AB  - Autistic disorder is a severe neurodevelopmental disorder most probably caused by
      a complex interaction of genetic factors. Several genomewide scans identified
      multipoint LOD score peaks in region 7q32. In this region, UBE2H encodes an E2
      enzyme of the ubiquitin-dependent proteolytic system. Mutations in another member
      of this system, the UBE3A gene, cause Angelman syndrome. The participation of E2
      (ubiquitin-conjugating enzymes) or E3 (ubiquitin ligases) enzymes in neural
      development recently emerged. Given its physical location and function, we
      examined UBE2H as a candidate for involvement in autistic disorder. We confirmed
      by reverse transcription-polymerase chain reaction that the UBE2H gene was
      expressed in the rat and the human central nervous system. The rat UBE2H and
      human UBE2H deduced amino acid sequences are identical. We screened the seven
      exons of the UBE2H gene in autistic patients using single-strand conformation
      analysis. We observed a silent A-->G transition at position 336. A case-control
      association study was performed using this A/G polymorphism. A significant
      association was found between the G allele and a subgroup of autistic patients
      with developmental quotient higher than 30 (P=0.004). Although further studies
      are required, these results suggest that the UBE2H gene could be one of the 7q
      susceptibility loci for autistic disorder.

PMID- 14639050
TI  - Clinical use of a simultaneous HPLC assay for indinavir, saquinavir, ritonavir
      and nelfinavir in children and adults.
AB  - PROTEASE INHIBITOR TDM: This study examines the importance of therapeutic drug
      monitoring (TDM) of protease inhibitors (PI) in adults and children infected with
      the human immunodeficiency virus (HIV). Pediatric patients were included because
      information in this population is limited. A high performance liquid
      chromatographic (HPLC) assay measured indinavir, saquinavir, ritonavir and
      nelfinavir simultaneously in 0.2 mL of plasma. Initially, the reliability,
      sensitivity and specificity of the assay were verified in stored samples of
      plasma from adult patients who had been receiving PIs. Non-detectable
      concentrations (ND) were <25-50 ng/mL. In 96 out of 293 stored samples from adult
      patients, selected randomly, concentrations of PIs were ND. In a second
      prospective study of 10 adults (9 mothers and one father, aged 24-42 years) and
      15 children (2.9-18 years) ND levels of PI were observed frequently (27% or 4 out
      of 15 pediatric subjects). In the latter study, drug-drug interactions, dosing
      errors, noncompliance and other important problems were identified and corrected.
      Routine monitoring and interpretation of PI concentrations (TDM) may improve the
      management of adult and pediatric patients infected with HIV, especially in those
      who fail to respond, develop adverse effects or viral resistance, or lack
      compliance.

PMID- 14639051
TI  - Intra- and interindividual variations in steady-state plasma concentrations of
      risperidone and 9-hydroxyrisperidone in schizophrenic patients treated
      chronically with various doses of risperidone.
AB  - The intra- and interindividual variability in apparent steady-state plasma levels
      of risperidone (RSP) and its metabolite 9-hydroxyrisperidone (9-OHRSP) in
      schizophrenic patients was investigated. Patients (n = 46, age 26.4 +/- 5.3
      years) with diagnosed schizophrenia were treated with a fixed daily oral dose of
      RSP (1-12 mg/d). The steady-state plasma samples from these patients were
      collected over a period of 5 years and a total of 549 visits. Plasma
      concentrations of RSP and 9-OHRSP were determined using a highly sensitive and
      specific LC-MS-MS method with a detection limit of 0.1 ng/mL. All plasma samples
      had measurable amounts of 9-OHRSP; however, RSP was nondetectable (<0.1 ng/mL) in
      18% of the plasma samples. 9-OHRSP levels were, on average, approximately 22
      times higher than those of RSP. The plasma levels of RSP and 9-OHRSP varied
      widely among patients receiving similar doses of RSP, and the intra- and
      interindividual variations of RSP and 9-OHRSP plasma levels were found to be
      large. The data indicated that there was no significant change in the steady
      state levels of either RSP or 9-OHRSP during the treatment period. Similarly, the
      dose-normalized concentration did not vary significantly during the treatment
      period or with the administered dose. The absence of RSP in many plasma samples
      (<0.1 ng/mL) and presence of 9-OHRSP at severalfold higher concentrations than
      RSP indicate that measuring plasma levels of RSP alone may lead to erroneous
      interpretation in plasma level monitoring studies. The current data support the
      fact that it is important to measure steady-state levels of total active moiety
      by analyzing both RSP and 9-OHRSP for plasma drug monitoring.

PMID- 14639052
TI  - Dose-adjusted cyclosporine c2 in a patient with jejunoileal bypass as compared to
      seven other liver transplant recipients.
AB  - Jejunoileal bypass (JIB) is a weight loss procedure in which malabsorption is
      produced by connecting a short length of proximal jejunum to the distal ileum.
      Because 90% of the small intestine is bypassed, it may have impact on the dose
      concentration response of oral cyclosporine (CsA). The authors characterized the
      dose-adjusted blood concentrations of CsA obtained 2 hours (C2) after oral
      microemulsion CsA (ME-CsA) in a liver transplant (LTx) subject with an intact
      JIB, as compared with those from seven LTx controls without JIB. The biliary
      reconstruction involved choledochocholedochostomy without external drainage in
      all patients. ME-CsA was administered via a nasogastric tube within 24 hours
      after graft reperfusion. Oral fluconazole was given prophylactically to the study
      subject only for 6 days after LTx. During the first week after LTx, the dose
      adjusted C2 (mean +/- SD) for the study subject and for controls was 53 +/- 10
      and 106 +/- 47 ng/mL, respectively (P < 0.001). The corresponding value during
      the period from day 7 to day 107 was 105 +/- 40 and 257 +/- 86 ng/mL,
      respectively (P < 0.001). Multiple linear regression revealed that dosage, days
      after LTx, and the presence of a JIB were all independent predictors of C2 (R2 =
      0.798, P = 0.037). Lack of bile resulting in malabsorption of ME-CsA was not
      thought to be significant contributor to her low dose-adjusted C2 because there
      was no external bile drainage and a portion of terminal ileum, where most bile
      acid reabsorption occurred, was still available after JIB. The fact that
      fluconazole failed to increase the dose-adjusted C2 in the study subject supports
      that enteric clearance of CsA may become clinically unimportant after JIB.
      Therefore, the low dose-adjusted C2 is most likely explained by the reduced bowel
      length and associated absorptive surface area after JIB. In conclusion, patients
      with JIB may require higher doses of ME-CsA.

PMID- 14639053
TI  - Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid
      arthritis.
AB  - SUMMARY: Hydroxychloroquine (HCQ) is an antimalarial drug that is also used as a
      second-line treatment of rheumatoid arthritis (RA). Clinically, the use of HCQ is
      characterized by a long delay in the onset of action, and withdrawal of treatment
      is often a result of inefficacy rather than from toxicity. The slow onset of
      action can be attributed to the pharmacokinetics (PK) of HCQ, and wide
      interpatient variability is evident. Tentative relationships between
      concentration and effect have been made, but to date, no population PK model has
      been developed for HCQ. This study aimed to develop a population PK model
      including an estimation of the oral bioavailability of HCQ. In addition, the
      effects of the coadministration of methotrexate on the PK of HCQ were examined.
      Hydroxychloroquine blood concentration data were combined from previous
      pharmacokinetic studies in patients with rheumatoid arthritis. A total of 123
      patients were studied, giving the data cohort from four previously published
      studies. Two groups of patients were included: 74 received hydroxychloroquine
      (HCQ) alone, and 49 received HCQ and methotrexate (MTX). All data analyses were
      carried out using the NONMEM program. A one-compartment PK model was supported,
      rather than a three-compartment model as previously published, probably because
      of the clustering of concentrations taken at the end of a dosing interval. The
      population estimate of bioavailability of 0.75 (0.07), n = 9, was consistent with
      literature values. The parameter values from the final model were: Cl = 9.9 +/-
      0.4 L/h, V = 605 +/- 91 L, ka = 0.77 +/- 0.22 hours(-1), t(tag) = 0.44 +/- 0.02
      hours. Clearance was not affected by the presence of MTX, and, hence, steady
      state drug concentrations and maintenance dosage requirements were similar. A
      population PK model was successfully developed for HCQ.

PMID- 14639054
TI  - Investigation of target plasma concentration-effect relationships for olanzapine
      in schizophrenia.
AB  - Olanzapine is an atypical antipsychotic effective in the treatment of
      schizophrenia. The present study has examined the potential use of target
      concentration monitoring of olanzapine in plasma as a marker of clinical response
      and an aid in patient management. Fifty-three patients (mean age 32 years; 40 M,
      13 F) with a DSM-IVR diagnosis of schizophrenia completed a 6-week trial of oral
      olanzapine. Participants received once-daily olanzapine, and their psychotic
      symptoms were measured with the PANSS (Positive and Negative Symptom Scale) on
      admission and again after 6 weeks. Responders were classified as having a >/=20%
      decrease in PANSS scores. Plasma olanzapine was quantified by high-performance
      liquid chromatography. Receiver operator characteristic (ROC) curve analysis was
      used to identify a break point in plasma olanzapine that might serve as a
      surrogate for PANSS classification, and the two methods were compared using the
      McNemar chi2 test. After 6 weeks the median olanzapine dose was 15 mg/d (range 5
      30 mg/d), and the mean plasma olanzapine was 32 micrograms/L at a mean of 13.5
      hours after dose. With the PANSS (total), there were 42 responders and 11
      nonresponders. ROC curve analysis for total PANSS identified a break point at 23
      micrograms/L plasma olanzapine, with the proportions of responders and
      nonresponders identified by PANSS and the plasma break point being similar.
      Similar break points were found for the positive, negative, and global PANSS
      subscores. Nevertheless, these relationships were very modest, and at best the
      target plasma olanzapine concentration identified only 20% more responders than
      nonresponders. We suggest that plasma olanzapine monitoring can be used for dose
      response optimization, but only to complement the normal clinical evaluation
      process.

PMID- 14639055
TI  - Serum concentrations of Levetiracetam in epileptic patients: the influence of
      dose and co-medication.
AB  - Levetiracetam (LEV) is a new antiepileptic drug approved as add-on therapy.
      Previous studies indicated that LEV has no relevant interactions with other
      antiepileptic drugs. The aim of this study was to investigate the influence of
      LEV dose, age, and co-medication on the serum concentration of LEV. In total, 363
      samples of 297 inpatients who fulfilled the inclusion criteria (e.g., trough
      concentration, body weight available) were investigated. A patient was considered
      twice only if his co-medication had been changed. The LEV serum concentration in
      relation to LEV dose/body weight [level-to-dose ratio, LDR,
      (microgram/mL)/(mg/kg)] was calculated and compared for the most frequent drug
      combinations. Analysis of covariance (using age as covariate) carried out on the
      log-transformed data showed that co-medication had a highly significant (P <
      0.001) effect on LEV serum concentrations. The median LDR of LEV was 0.32 for LEV
      + phenytoin, 0.32 for LEV + carbamazepine, 0.34 LEV + oxcarbazepine, 0.45 for LEV
      + lamotrigine, 0.46 for LEV + phenobarital, 0.52 for LEV monotherapy, 0.53 for
      LEV + valproic acid, and 0.54 LEV + valproic acid + lamotrigine. In co-medication
      with phenytoin (P < 0.001), carbamazepine (P < 0.001), and oxcarbazepine (P <
      0.004), the LDR of LEV was significantly lower than it was with LEV monotherapy,
      whereas the LDR of LEV of patients on co-medication with valproic acid or
      lamotrigine did not differ significantly from the LDR of LEV of patients on LEV
      monotherapy (P > 0.05). Regression analysis including all 363 samples confirmed
      that other drugs (e.g., phenytoin, carbamazepine) lower LEV concentrations. In
      addition to co-medication, age had a significant effect on clearance of LEV.
      Children had lower LEV concentrations than adults on the same LEV dose per body
      weight. In contrast to other studies, our data point out that other enzyme
      inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) can moderately
      decrease LEV serum concentrations (by 20-30%). However, our observations should
      be confirmed by prospective pharmacokinetic studies.

PMID- 14639056
TI  - Influence of dosage, age, and co-medication on plasma topiramate concentrations
      in children and adults with severe epilepsy and preliminary observations on
      correlations with clinical response.
AB  - The influence of dosage, age, and co-medication on plasma topiramate (TPM)
      concentrations at steady state was investigated in 51 patients aged 3 to 30
      years. All patients had chronic active epilepsy, and most were receiving
      concomitant medication with enzyme-inducing anticonvulsants (carbamazepine and
      phenobarbital). Plasma TPM concentrations were determined by a specific
      immunoassay in samples obtained before the morning dose. Thirty-five patients
      could be evaluated prospectively at different dose levels, and the relationship
      between plasma TPM concentration and dosage was linear over the assessed dose
      range (1.8 to 10.0 mg/kg) both in adults and in children. The influence of age on
      pharmacokinetic parameters could be assessed only for the 42 patients co
      medicated with enzyme inducers. In these patients dose-normalized plasma TPM
      concentrations correlated positively with age (r = 0.59, P < 0.0001), where
      apparent oral clearance values (CL/F) were inversely related to age (r = 0.73, P
      < 0.0001). In particular, CL/F values in children aged less than 10 years (112 +/
      82 mL/kg/h, mean +/- SD, n = 14) were almost three times as high as those
      observed in patients aged >15 to 30 years (42 +/- 16 mL/kg/h, n = 17), whereas
      the CL/F value in children aged 10 to 15 years (66 +/- 22 mL/kg/h, n = 11) was
      intermediate between those found in the two other age groups. Patients not
      receiving enzyme-inducing AEDs showed lower CL/F values than did age- and gender
      matched patients on enzyme-inducing co-medication. A preliminary evaluation of
      the relationship between plasma TPM concentration and therapeutic response could
      be made in 41 patients. No significant difference in drug concentration was
      detected between patients showing a greater than 50% reduction in seizure
      frequency compared with baseline (5.9 +/- 2.2 micrograms/mL, n = 30) and those
      having no clinical improvement (5.2 +/- 2.2 micrograms/mL, n = 11). Likewise,
      there was no consistent relationship between plasma TPM concentration and
      appearance of adverse effects. These results indicate that plasma TPM
      concentrations are linearly related to dosage both in adults and in children and
      that children aged <10 years require much greater body weight-adjusted dosage to
      achieve drug levels comparable to those observed in young adults. The marked
      increase in TPM clearance caused by enzyme-inducing co-medication was confirmed.

PMID- 14639057
TI  - Poor reliability of therapeutic drug monitoring data for haloperidol and
      bromperidol using enzyme immunoassay.
AB  - Therapeutic drug monitoring (TDM) services for plasma concentrations of
      haloperidol and bromperidol using enzyme immunoassay (EIA) methods are available
      in Japan, whereas high-performance liquid chromatographic (HPLC) methods are
      preferred in other countries. To compare these methods, we took 54 plasma samples
      for haloperidol and 91 plasma samples for bromperidol from schizophrenic patients
      receiving haloperidol or bromperidol, and the samples were measured using both
      commercial EIA and HPLC methods. Significant linear correlations were found
      between the two methods in determining haloperidol (EIA = 1.351 x HPLC + 1.39; r
      = 0.934, P < 0.001) and bromperidol (EIA = 1.420 x HPLC + 0.712; r = 0.956, P <
      0.001) concentrations, but plasma concentrations using the EIA kits were
      approximately 92% (95% CI; 53-131%) and 62% (54-70%) higher than those using HPLC
      for haloperidol and bromperidol, respectively. Mean (and range) plasma
      concentrations of reduced metabolites were 54% (30-92%) and 55% (29-111%) of
      those of haloperidol and bromperidol, respectively. The present study suggests
      that reduced metabolites are included to a considerable degree in TDM data using
      the EIA kits. Therefore, some limitation of TDM data of haloperidol and
      bromperidol using the EIA kits, ie, high precision but poor accuracy, should be
      kept in mind.

PMID- 14639058
TI  - Intentional warfarin overdose.
AB  - Warfarin toxicity is common and usually results from dose changes or drug
      interactions. There are few reported cases of intentional overdose. The
      management of warfarin overdose is usually complicated by the patient using
      warfarin therapeutically, often for a mechanical heart valve or pulmonary embolus
      prophylaxis. Untreated patients have a significant bleeding risk, but treatment
      carries a significant risk of complete reversal of anticoagulation and consequent
      risk of thrombosis. The objective of this study was to describe warfarin
      overdoses and complications of treatment and develop a safe approach to
      management. Three patients are described. Two patients received a single 10-mg
      dose of vitamin K. Both required anticoagulation, and in one, warfarin resistance
      persisted for 2 weeks. In a third patient serial INR, factor levels and warfarin
      concentrations were measured, and incremental doses of vitamin K (up to 7.5 mg)
      were given based on INR. This patient did not require anticoagulation, and
      regular warfarin therapy was recommenced after 4 days. Patients intentionally
      overdosing on warfarin can be classified into three groups based on preexisting
      indications for warfarin: nontherapeutic, moderate risk, and major risk for
      thromboembolic complications. All patients should have regular INR measurements
      (6-hourly) to catch rapid rises. Patients not on warfarin therapeutically can be
      given 10 mg of vitamin K1 and repeat INRs as an outpatient. Titrating intravenous
      vitamin K with doses of 0.5 to 2.0 mg when INR > 5 is appropriate to reduce INR
      without causing warfarin resistance. The high-risk group must be kept
      anticoagulated, and warfarin resistance avoided.

PMID- 14639059
TI  - Impact of lowering the screening and confirmation cutoff values for urine drug
      testing based on dilution indicators.
AB  - Many clinical and forensic toxicology laboratories establish criteria for
      identifying a random urine specimen submitted for drug screening as being
      "normally concentrated" or "dilute" by incorporating creatinine analysis and/or
      specific gravity measurement into their testing protocols. The objective of this
      study is to describe the importance of urine creatinine analysis and specific
      gravity measurements in the Correctional Service of Canada (CSC) drug-testing
      program. The CSC program uses the Substance Abuse and Mental Health Services
      Administration (SAMHSA) creatinine cutoff value (20 mg/dL) mandated for workplace
      drug testing in the United States. In the CSC program, urine specimens must have
      a creatinine concentration <20 mg/dL and specific gravity value </=1.003 to be
      considered dilute. The CSC program also incorporates lower drug/drug metabolite
      screening and confirmation cutoff values (dilution protocol) for specimens that
      are administratively defined as dilute. Seventy-nine hundred and twelve urine
      specimens from 2000 to 2002 (6.8% of total workload) were defined as dilute.
      Twenty-six percent of all dilute specimens (n = 2054) screened positive for one
      or more drugs using the SAMHSA cutoff values. The screening-negative dilute
      specimens were taken through the dilution protocol scheme with lower screening
      cutoff values and confirmation cutoff concentrations at the lower limits of
      quantification (LLOQ) for each method. Over 1100 of the 5858 dilute urine
      specimens (18.8%) confirmed positive for one or more drugs in 2000 to 2002 when
      taken through the dilution protocol scheme. CSC workload is separated based on
      whether specimens are referred from institutions or from community settings (such
      as parolee programs). The positive rate for dilute specimens averaged 18.2% from
      CSC institutions and 22.3% from specimens collected from parolee specimens in
      2000 to 2002. The drugs most often confirmed in dilute specimens from
      institutions were cannabinoids (annual positive rate ranged from 13.7 to 18%) and
      codeine and/or morphine (ranged from 0.2 to 2.8%). The drugs most often confirmed
      in dilute urine specimens from community settings in 2000-2002 were cannabinoids
      (annual positive rate ranged from 10.3 to 12.5%) and cocaine metabolite (ranged
      from 6.6 to 10.3%). In conclusion, one can reduce the false-negative rate for
      drugs of abuse in urine drug testing programs by incorporating lower screening
      and confirmation cutoff (eg, LLOQ) concentrations for dilute specimens that
      screen negative for drugs of abuse when using the SAMHSA mandated screening and
      confirmation cutoff concentrations.

PMID- 14639060
TI  - The utility of the history and clinical signs of poisoning in childhood: a
      prospective study.
AB  - The authors aimed to evaluate the utility of the history and clinical signs for
      predicting ingestion of poisons in children. A prospective cohort study was
      performed of all patients presenting with suspected poisoning to a pediatric
      emergency department over a 13-month period. Clinical data were collected on a
      preformatted consultation sheet. Urine drug screens (UDS) were analyzed by gas
      chromatography/mass spectrometry (GC/MS). Serum toxicologic tests were performed
      when clinically indicated. The sensitivity, specificity, positive predictive
      values (PPV), and negative predictive values (NPV) of the history and clinical
      signs were calculated, first using UDS and, second, using all available
      toxicologic tests as the gold standards. Of 249 patients, 110 (46%) had a UDS
      performed. The purported poison ingested was potentially identifiable by GC/MS in
      57 (52%) of these UDS. Only the results from these 57 UDS were included in our
      statistical analysis. Overall, the suspected poison was identified in 33 (58%) of
      the 57 UDS. Similarly, in the less than 5 years age subgroup, 28 (56%) of 50 UDS
      were positive. Odor on the breath (PPV 100%), followed by symptoms consistent
      with poisoning (PPV 92%) and presence of poison on clothes (PPV 86%) were the
      most useful predictors of a positive UDS. Similar results were obtained when all
      available toxicologic tests were used as the gold standard. The best clinical
      predictors of poisonous ingestion in children were found to be odor on the
      breath, symptoms consistent with poisoning, and presence of poison on the
      patient's clothes. Approximately 40% of children who present with poisoning have
      not been exposed to the putative toxin.

PMID- 14639061
TI  - Photophobia in a patient with high indinavir plasma concentrations.
AB  - An HIV-infected male patient experienced photophobia after a change in dosing
      regimen that resulted in substantially higher indinavir plasma levels as compared
      with a reference population. High indinavir levels were suspected to be the cause
      of photophobia in this patient.

PMID- 14639062
TI  - Polymorphisms in the CYP 2D6 gene: association with plasma concentrations of
      fluoxetine and paroxetine.
AB  - Most antidepressants are metabolized by cytochrome P450 (CYP) 2D6, and it is well
      known that there may be significant interindividual variation in the capacity to
      metabolize xenobiotics. About 7 to 10% of whites are poor metabolisers (PM), and,
      on the contrary, about 5% are ultrarapid metabolizers (UM), inducing very
      different rates in the transformation of antidepressants extensively metabolized
      by CYP 2D6. CYP 2D6 polymorphism can be a potential risk factor for the
      development of side effects or a reason for the poor efficacy of the treatment.
      Various probe drugs may be used for phenotyping CYP 2D6, but genotyping is now
      available using leukocyte DNA and is independent of concomitant drug use. In this
      study, we used PCR-based methods for the identification of CYP 2D6 genotypes in
      49 patients receiving standard doses of fluoxetine or paroxetine and found that
      plasma concentration of the antidepressant drugs was significantly correlated
      with genetic status. In one patient who displayed CYP 2D6 gene duplication (UM),
      paroxetine plasma concentration was extremely low. In PM fluoxetine-treated
      patients, drug plasma concentration was significantly higher than that seen in
      extensive metabolizers.

PMID- 14639063
TI  - TDM: report concentration, Css, rather than area under the curve, AUC.

PMID- 14639064
TI  - Editorial overview: current opinion in critical care-renal problems.

PMID- 14639065
TI  - Acid-base and electrolyte analysis in critically ill patients: are we ready for
      the new millennium?
AB  - PURPOSE OF REVIEW: Disorders of acid-base and electrolytes are commonly seen in
      critically ill patients. The presence of these disorders typically signals the
      development of an underlying pathology. These disturbances can be severe and are
      often associated with worse outcome. Indeed, metabolic acidosis is one of the
      ways we quantify organ failure. Although acid-base and electrolyte disorders may
      be a result of the underlying pathophysiology (eg, renal failure, respiratory
      failure, shock), they may also result from the way in which we manage critically
      ill patients. RECENT FINDINGS: The application of the physical-chemical approach
      to acid-base analysis has led to recent developments in the identification and
      quantification and understanding of mechanisms for acid-base disorders commonly
      found in critically ill patients. Examples include a better understanding of the
      role of electrolytes (especially sodium and chloride) and weak acids in the
      pathophysiology of acid-base disorders, the implication of acid-base derangements
      on the inflammatory process and organ perfusion, and the importance of
      resuscitation fluid composition. SUMMARY: By adopting a physical-chemical
      approach to acid-base analysis we are gaining insight to the complexities of acid
      base disorders and how their treatments may affect outcome.

PMID- 14639066
TI  - Pharmacologic treatment of acute renal failure in sepsis.
AB  - The pathophysiology of acute renal failure in sepsis is complex and includes
      intrarenal vasoconstriction, infiltration of inflammatory cells in the renal
      parenchyma, intraglomerular thrombosis, and obstruction of tubuli with necrotic
      cells and debris. Attempts to interfere pharmacologically with these
      dysfunctional pathways, including inhibition of inflammatory mediators,
      improvement of renal hemodynamics by amplifying vasodilator mechanisms and
      blocking vasoconstrictor mechanisms, and administration of growth factors to
      accelerate renal recovery, have yielded disappointing results in clinical trials.
      Interruption of leukocyte recruitment is a potential promising approach in the
      treatment of septic acute renal failure, but no data in humans are presently
      available. Activated protein C and steroid replacement therapy have been shown to
      reduce mortality in patients with sepsis and are now accepted adjunctive
      treatment options for sepsis in general.

PMID- 14639067
TI  - Prevention and nondialytic treatment of acute renal failure.
AB  - Based on the progress made during the last few years in understanding the
      pathophysiology of acute renal failure, a plethora of therapeutic drug and
      nondrug interventions have been developed and tested in animal and human forms of
      this disease. The first part of this article focuses on the role of volume
      expansion and vasopressors in the prevention and treatment of acute renal failure
      in the critically ill. From all prophylactic measures that have been proposed,
      volume expansion, or at least correction of volume depletion, remains the most
      efficient and most evidence-based intervention in these patients. Norepinephrine
      is, out of all the vasopressors, probably the most appropriate to use in cases of
      hypotension, provided circulating volume is adequate. In hypotensive septic
      patients, vasopressin has been shown to be useful. Direct renal vasodilating
      substances, the most popular still being low-dose dopamine, have never been
      proved to be useful in carefully performed prospective trials. Moreover dopamine
      especially is associated with a number of side effects and complications. From
      the agents acting on tubular factors, the diuretic mannitol and loop diuretics
      are the most prescribed. Only in specific situations such as rhabdomyolysis and
      kidney transplant surgery has it been shown that mannitol was able to prevent
      acute renal failure. The loop diuretics are able, after establishing adequate
      circulating volume, to promote diuresis in some forms of oliguric acute renal
      failure; however, some recent papers have shown that the administration of loop
      diuretics may actually be associated with increased mortality and delayed
      recovery of renal function. The last few years have seen a number of trials with
      acetylcysteine in the prevention of mainly radiocontrast nephropathy. Although
      the results are still conflicting, the majority indicates that acetylcysteine,
      when applied together with adequate volume expansion, may be a useful drug to
      incorporate in the standard treatment procedures in patients at risk for acute
      renal failure. Interventions to stimulate the recovery process of the damaged
      kidney with growth factors, although theoretically sound, have thus far not led
      to successful results.

PMID- 14639068
TI  - Dialysis strategies in critically ill acute renal failure patients.
AB  - PURPOSE OF REVIEW: Acute renal failure requiring dialysis is a frequent
      complication in critically ill patients, with a high morbidity and mortality.
      Until now, no evidence-based guidelines on the optimal treatment of acute renal
      failure on the ICU are available. This article reviews recent publications that
      shed light on several specific topics, like optimal treatment modality, dose of
      dialysis, type of dialysis membrane, and new developments such as slow extended
      daily dialysis. RECENT FINDINGS: For a long time, it has been claimed that
      continuous renal replacement therapies were superior to intermittent
      hemodialysis. Several recent articles addressed this topic, but none of them
      could demonstrate superiority of one of the two modalities. A meta-analysis
      confirmed this lack of differences in outcome. A landmark study underscored the
      importance of dose of dialysis in continuous renal replacement therapy. Although
      a comparable study in intermittent hemodialysis is still lacking, it was shown
      that daily dialysis is an absolute prerequisite for adequate intermittent
      hemodialysis. A meta-analysis further demonstrated that the use of biocompatible
      membranes can influence patient survival positively, without effect on recovery
      of renal function. Slow extended daily dialysis emerged as a hybrid renal
      replacement therapeutic modality and has promising features because it combines
      the advantages of both continuous renal replacement therapy and intermittent
      hemodialysis. SUMMARY: Adequate dialysis is needed to reduce mortality related to
      acute renal failure in ICU patients. This necessitates an approach that is
      completely different from that in chronic renal failure.

PMID- 14639069
TI  - The pathogenesis of septic acute renal failure.
AB  - PURPOSE OF REVIEW: Acute renal failure is a serious condition that affects as
      many as 20% of ICU patients. The most common causes of acute renal failure in the
      ICU patient are severe sepsis and septic shock. The mortality of acute renal
      failure in septic critically ill patients remains high despite our increasing
      ability to support vital organs. This is partly the result of our poor
      understanding of the pathogenesis of sepsis-induced renal dysfunction.
      Accordingly, a review of our current understanding of the pathogenesis of septic
      acute renal failure is timely and relevant. RECENT FINDINGS: Throughout the past
      half century, acute renal failure of acute illness has essentially been
      considered a hemodynamic disease caused by kidney ischemia, a view derived by
      findings in animal models. Unfortunately most such models are greatly deficient
      in that they do not reproduce the high cardiac output, low systemic vascular
      resistance state typically seen during human sepsis. Furthermore, most models
      inducing so-called acute tubular necrosis are based on ischemia-reperfusion
      (renal artery clamping), an event with little relevance to human sepsis. Recent
      research highlights a new possible and emerging concept for the pathogenesis of
      septic acute renal failure: acute apoptosis. This concepts fits well with the
      typical paucity of histologic changes seen in so-called acute tubular necrosis
      and with growing evidence of a role for apoptosis in organ injury during sepsis
      and inflammation in general. Furthermore, the authors present evidence that some
      potential treatments recently shown to affect the mortality of critically ill
      patients, (activated protein C, intensive insulin treatment, and low-volume
      mechanical ventilation) might have antiapoptotic activity. SUMMARY: This review
      suggests that, on the evidence available, septic acute renal failure is more
      likely to be an immune or toxic state rather than simply a hemodynamic condition.
      The authors speculate that future insights into its pathogenesis might lead to a
      paradigm shift away from the concept of acute tubular necrosis, which has never
      been convincingly shown in sepsis, to that of acute tubular apoptosis.

PMID- 14639070
TI  - Traumatic brain injury.
AB  - PURPOSE OF REVIEW: Management of the patient with traumatic brain injury is a
      rapidly advancing field, characterized in recent years by an improved
      understanding of intracranial pathophysiology and ways in which outcomes can be
      improved. Many traditional therapies, such as fluid restriction and
      hyperventilation, have been called into question and are no longer recommended.
      Other proposed therapies, such as deliberate hypothermia, remain controversial.
      This detailed review of the recent literature helps the reader come to an
      understanding of current scientific and evidence-based practices in this area,
      with emphasis on those therapies most likely to be of use to the practicing
      intensivist. RECENT FINDINGS: High-quality care of the traumatic brain injury
      patient demands the integrated activities of a number of different medical and
      nursing specialties. The best outcomes today are achieved by those systems that
      are able to focus as a team on the collective goal of minimizing secondary brain
      injury, and the respiratory therapist adjusting the patient's mechanical
      ventilation may be just as important to this effort as the attending
      neurosurgeon. Although the search for new diagnostic, prognostic, and therapeutic
      modalities continues (many of the more promising of which are reviewed in this
      article), it is clear that there exists no "silver bullet" therapy that will help
      all patients. Instead, it is the systematic integration and application of many
      small advances that will ultimately lead to better outcomes. SUMMARY: Some issues
      in traumatic brain injury have now been resolved, and specific recommendations
      can be made. Fluid therapy directed toward a euvolemic state is now universally
      recommended, for example, as is the role of intracranial pressure monitoring.
      Other areas, such as the use of hypertonic saline, remain controversial. In both
      cases the authors have made an effort to cite the most recent literature, so that
      readers can draw their own conclusions from the original source material.

PMID- 14639071
TI  - Organized trauma care: does volume matter and do trauma centers save lives?
AB  - PURPOSE OF REVIEW: Trauma is the leading cause of death during the first four
      decades of life. Since the 1970s, organized systems for trauma care, including a
      prehospital emergency medical system and a network of hospitals designated as
      trauma centers, have been developed. The model of the trauma system and its
      efficacy have been reviewed. RECENT FINDINGS: Fundamental to the trauma system is
      its recognition in the field and the transportation to a trauma center of
      patients with more serious injuries. Each trauma center has to treat at least 240
      severe trauma patients per year to increase experience. It is cost-effective that
      less severely injured patients be treated in nontrauma center's acute care
      facilities, according to the inclusive system model. The effectiveness of trauma
      systems has been investigated by comparing postsystem with presystem trauma care
      with three methods: panel evaluation of preventable death rates, comparison of
      observed survival with expected probability of survival derived from large trauma
      registries, and evaluation of population-based general databases. These studies
      have demonstrated a decrease in preventable death rate and an increase in
      survival after system implementation. All these studies have been classified as
      providing weak class III evidence. However, with a large sample size and when
      properly designed, they generate important information regarding appropriateness
      of care delivered. SUMMARY: Concentration of severely injured patients in trauma
      centers is associated with better outcomes. Population-based investigations
      provide the strongest evidence regarding effects of the trauma system on patient
      outcomes, other than survival outcome measures because long-term functional
      status may be more appropriate.

PMID- 14639072
TI  - Hemorrhage in pelvic fracture: who needs angiography?
AB  - Pelvic fractures are rare but potentially devastating injuries. An understanding
      of the bony and peripelvic anatomy along with common patterns and the
      classification of the injury are of critical importance in their management.
      These form the basis for a general treatment algorithm for pelvic fracture
      patients. Angiographic embolization is time-consuming and often delayed.
      Hemodynamic instability with unstable pelvic fracture is therefore best
      approached with a combination of pelvic emergency stabilization (C-clamp) and
      surgical hemostasis by pelvic tamponade. This is especially true for critically
      injured patients in extremis.

PMID- 14639073
TI  - Is field intubation useful?
AB  - The establishment and maintenance of an adequate airway is often the single most
      important initial therapy provided to a victim of severe injury. This may be
      accomplished by simple techniques such as placement of an oral or nasopharyngeal
      airway as well as bag-mask ventilation techniques. More advanced techniques such
      as endotracheal intubation require a higher level of training and expertise for
      both prehospital and hospital providers. Although paramedics routinely practice
      endotracheal intubation in the field, there are increasing reports on the many
      potential risks associated with these procedures as well as increased morbidity
      and mortality in both pediatric and adult patients. These data have important
      implications for field airway management in the critically ill trauma patient.

PMID- 14639074
TI  - Diagnosis of blunt cerebrovascular injuries.
AB  - PURPOSE OF REVIEW: Blunt cerebrovascular injuries (BCVI) are being increasingly
      recognized. The optimal criteria for screening, and the best diagnostic test,
      remain a matter of controversy. This review analyzes the available literature to
      propose management guidelines for the diagnosis of BCVI. RELEVANT FINDINGS: A
      number of centers are screening asymptomatic patients for BCVI. The criteria vary
      from center to center. The incidence of injuries diagnosed is proportional to the
      breadth of screening criteria. Noninvasive diagnostic modalities such as duplex
      ultrasonography, computed tomographic angiography, and magnetic resonance
      angiography have been proposed as screening tools. Although they are all capable
      of identifying many injuries, prospective comparisons reveal inaccuracies.
      SUMMARY: Screening for BCVI is appropriate. Institutions should adopt formal
      criteria, recognizing that more restrictive criteria are likely to miss injuries.
      Noninvasive modalities must be used with caution, because they have been found to
      be inferior to arteriography.

PMID- 14639075
TI  - Special considerations in geriatric injury.
AB  - PURPOSE OF REVIEW: As the elderly population expands and adopts increasingly more
      active lifestyles, trauma and critical care practitioners will be faced with
      providing care for greater numbers of severely injured patients. However, because
      of their associated preexisting medical conditions and poor relative physiologic
      reserve, geriatric patients have higher mortality rates and poorer long-term
      functional outcomes than their younger counterparts. A thorough understanding of
      the causes for these disparate outcomes is critical if successful strategies and
      treatments for this unique patient population are to be developed. RECENT
      FINDINGS: The currently available geriatric trauma literature is largely
      descriptive and retrospective, and does not provide ready explanations or
      solutions for the substantially worse outcomes experienced by this patient
      population. It does appear that outcomes are improved by providing early and
      aggressive care in designated trauma centers, yet undertriage remains a
      significant problem. Early admission to an ICU has been recommended, but its
      benefits remain unproved. Significant differences exist between older and younger
      patients in injury patterns, and in the frequency and type of complications These
      differences in turn demand prompt diagnostic approaches, aggressive treatment,
      and unique prevention strategies. SUMMARY: Ironically, the field of geriatric
      trauma is still in its infancy. Given the relation between advanced age,
      associated preexisting medical conditions, and poor physiologic reserve, a poor
      outcome may be inevitable by the time the geriatric patient presents for medical
      attention. Greater emphasis should therefore be placed on injury prevention
      efforts in this patient population. There is a dire need for well-designed
      prospective studies in geriatric trauma.

PMID- 14639076
TI  - Research ethics and consent in the intensive care unit.
AB  - PURPOSE OF REVIEW: The subject of research ethics and informed consent in the ICU
      has recently received unprecedented attention during the past year, the reasons
      for which are reviewed herein. RECENT FINDINGS: The controversy over research
      design and informed consent issues in studies conducted by the Acute Respiratory
      Distress Syndrome Network in the United States have been responsible for much of
      the attention on research ethics. So has the draft directive to create a
      harmonization of the provisions governing clinical trials within the European
      Union. These and other factors have prompted renewed interest in the proper
      design of clinical trials, the difficulty of obtaining informed consent for
      research from critically ill patients and their surrogates, conflicts of interest
      on the part of investigators and their institutions, the need for improving
      institutional protections for human subjects, and the desirability of clarifying
      the investigator-subject relationship. SUMMARY: Clinical trials should compare
      new therapies with "standard" ones if a standard of care exists. Surrogate
      consent is required for research involving most critically ill subjects, and
      state laws in the United States and national statutes in Europe should reflect
      this requirement. Conflicts of interest should be identified at both the
      individual and the institutional levels. Institutional review boards should focus
      on ethical issues after conflicts of interest are evaluated. Making the
      investigator-subject relationship transparent should help protect subjects.

PMID- 14639077
TI  - Communication with family members of patients dying in the intensive care unit.
AB  - In intensive care units the patient is usually unconscious and/or incompetent so
      that the relationship shifts to the family. Interactions between caregivers and
      families usually follow one of three models. In the first model, a family
      representative receives information from the caregivers but does not participate
      in decisions or physical care. In the second model, the ICU caregivers attempt to
      provide care consistent with the patient's wishes and values as described by the
      family. In the third model, the family members communicate their own wishes,
      provide physical care to the patient, and participate in medical decision-making.
      After a description of the studies that measured the quality of information
      provided to ICU families and by discussing the extent to which respecting the
      principle of patient autonomy is feasible in the ICU, we will review the
      literature on studies that identified specific needs of families of dying
      patients and specific challenges faced by intensivists as they seek to inform the
      families of dying patients. The need for family-centered care and for a better
      communication within the patient-family-caregiver trio is also highlighted.

PMID- 14639080
TI  - Managing adverse health symptoms: a fruitful core of nursing research warranting
      continued cultivation.

PMID- 14639081
TI  - An HIV self-care symptom management intervention for African American mothers.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection has become a serious
      health problem for low-income African American women in their childbearing years.
      Interventions that help them cope with feelings about having HIV and increase
      their understanding of HIV as a chronic disease in which self-care practices,
      regular health visits, and medications can improve the quality of life can lead
      to better health outcomes. OBJECTIVE: This study aimed to determine the efficacy
      of an HIV self-care symptom management intervention for emotional distress and
      perceptions of health among low-income African American mothers with HIV. METHOD:
      Women caregivers of young children were randomly assigned to self-care symptom
      management intervention or usual care. The intervention, based on a conceptual
      model related to HIV in African American women, involved six home visits by
      registered nurses. A baseline pretest and two posttests were conducted with the
      mothers in both groups. Emotional distress was assessed as depressive symptoms,
      affective state, stigma, and worry about HIV. Health, self-reported by the
      mothers, included the number of infections and aspects of health-related quality
      of life (i.e., perception of health, physical function, energy, health distress,
      and role function). RESULTS: Regarding emotional distress, the mothers in the
      experimental group reported fewer feelings of stigma than the mothers in the
      control group. Outcome assessments of health indicated that the mothers in the
      experimental group reported higher physical function scores than the control
      mothers. Within group analysis over time showed a reduction in negative affective
      state (depression/dejection and tension/anxiety) and stigma as well as infections
      in the intervention group mothers, whereas a decline in physical and role
      function was found in the control group. CONCLUSIONS: The HIV symptom management
      intervention has potential as a case management or clinical intervention model
      for use by public health nurses visiting the home or by advanced practice nurses
      who see HIV-infected women in primary care or specialty clinics.

PMID- 14639082
TI  - Hispanic chronic disease self-management: a randomized community-based outcome
      trial.
AB  - BACKGROUND: In light of health disparities and the growing prevalence of chronic
      disease, there is a need for community-based interventions that improve health
      behaviors and health status. These interventions should be based on existing
      theory. OBJECTIVE: This study aimed to evaluate the health and utilization
      outcomes of a 6-week community-based program for Spanish speakers with heart
      disease, lung disease, or type 2 diabetes. METHOD: The treatment participants in
      this study (n = 327) took a 6-week peer-led program. At 4 months, they were
      compared with randomized wait-list control subjects (n = 224) using analyses of
      covariance. The outcomes for all the treatment participants were assessed at 1
      year, as compared with baseline scores (n = 271) using t-tests. RESULTS: At 4
      months, the participants, as compared with usual-care control subjects,
      demonstrated improved health status, health behavior, and self-efficacy, as well
      as fewer emergency room visits (p <.05). At 1 year, the improvements were
      maintained and remained significantly different from baseline condition.
      CONCLUSIONS: This community-based program has the potential to improve the lives
      of Hispanics with chronic illness while reducing emergency room use.

PMID- 14639083
TI  - Predicting breast cancer-related lymphedema using self-reported symptoms.
AB  - OBJECTIVES: This study aimed to determine the accuracy of using self-reported
      signs and symptoms to identify the presence of lymphedema as well as the
      usefulness of identifying clinically measurable lymphedema on the basis of
      certain symptoms elicited by the Lymphedema Breast Cancer Questionnaire (LBCQ).
      METHODS: This analysis used logistic regression to identify symptoms predictive
      of differences between symptom experiences of participants belonging to two
      distinct groups (study A): those with known post-breast cancer lymphedema (n =
      40) and those in a control group of women with no history of breast cancer or
      lymphedema (n = 40). Symptoms in this model of best fit were used to examine
      their relation to limb circumferences of breast cancer survivors in a second
      independent data set (study B; n = 103) in which a diagnosis of known lymphedema
      was not previously determined using symptom experiences. RESULTS: The presence of
      lymphedema was predicted by three symptoms comprising a model of best fit for
      study A (c =.952): "heaviness in past year," "swelling now," and "numbness in
      past year." Using this model, prediction of absolute maximal circumferential limb
      difference (i.e., >or=2 cm) in study B showed that "heaviness in the past year"
      (p =.0279) and "swelling now" (p =.0007) were predictive. "Numbness in the past
      year" was not predictive. However, those with lesser limb differences reported
      this symptom more often. CONCLUSIONS: The findings suggest that changes in
      sensations may be indicators of early lymphedema or other treatment-related
      sequelae that must be assessed carefully at each follow-up visit and over time. A
      combination of symptom assessment and limb volume measurement may provide the
      best clinical assessment data for identifying changes associated with post-breast
      cancer lymphedema.

PMID- 14639084
TI  - Nursing intervention research and quality of care: influencing the future of
      healthcare.
AB  - BACKGROUND: Improvement of healthcare in the United States is a national
      priority. Nursing intervention science can contribute substantially to addressing
      this priority. OBJECTIVES: The aim of this study was to describe strategies
      needed to maximize the base of nursing intervention science. METHODS: The study
      involved a review of reports on the state of quality in healthcare and an
      examination of nurse-led intervention studies funded by the National Institute of
      Nursing Research aimed at improving healthcare processes and outcomes. RESULTS:
      Nursing has contributed valuable data regarding the meaning of quality from the
      perspectives of individuals, families, and communities. Increased efforts are
      needed to ensure that this science informs ongoing initiatives to define, assess,
      and improve the quality of healthcare. CONCLUSIONS: Nurse-led intervention
      research is making significant contributions to the advancement of the science
      underpinning quality healthcare. However, the message regarding the substantive
      and unique contributions of this body of work needs to be disseminated more
      broadly. Future nursing intervention research aimed at improving healthcare
      quality should consider individual behavior in a broader context, extend the
      traditional foci of interventions, and be grounded in the sciences of multiple
      disciplines.

PMID- 14639085
TI  - Effects of gender and preference for information and control on anxiety early
      after myocardial infarction.
AB  - BACKGROUND: Men and women differ in anxiety, which is one of the most stressful
      outcomes of an acute myocardial infarction (AMI). This anxiety may be moderated
      by coping styles of preference for information and control. OBJECTIVE: This study
      aimed to examine the relation of gender and preference for information and
      control to anxiety during the critical care period after AMI. METHODS: As part of
      a larger study on complications after AMI, a descriptive cross-sectional
      multicenter one-group investigation designed with a convenience sample of AMI
      patients admitted to acute care units was conducted. Within the first 48 hours
      after the patients were admitted to the hospital, anxiety was assessed using the
      State Anxiety Inventory, and preference for information and control was measured
      using the Krantz Health Opinion Survey. RESULTS: The sample of AMI patients (N =
      410) was 68% male, 87% White, 68% married. The women were significantly older
      than the men (p <.05) and significantly more anxious (p <.05). Multiple stepwise
      regression analysis with a control for age demonstrated that neither preference
      for information nor preference for control moderated the relation of gender and
      anxiety. CONCLUSIONS: The women expressed greater anxiety than the men. However,
      the men and women were similar at all levels of anxiety in their preference for
      information and control. The search for other factors related to the stress of
      AMI will help healthcare providers design effective interventions to reduce
      anxiety among men and women.

PMID- 14639086
TI  - A cluster of symptoms over time in patients with lung cancer.
AB  - BACKGROUND: Patients with lung cancer present late in the disease and have
      multiple symptoms. Previous research has shown the symptom cluster of fatigue,
      weakness, weight loss, appetite loss, nausea, vomiting, and altered taste to be
      present at time of lung cancer diagnosis. OBJECTIVES: The study determined
      whether the symptom cluster identified at the time of diagnosis remained 3 and 6
      months later, and whether there was a difference in the mean number of symptoms
      and the mean level of symptom severity over time. The relation of the severity
      rating for individual symptoms at the time of diagnosis and at 3 and 6 months
      after diagnosis was examined. Predictors for the number of symptoms and whether
      the symptom cluster was predictive of death were determined. METHODS: Secondary
      analysis of an existing data set for 112 patients with newly diagnosed lung
      cancer assessed at diagnosis and at 3 and 6 months was performed and determined
      whether they were alive or dead 19 months after diagnosis. RESULTS: The cluster
      of seven symptoms had internal consistency that remained at 3 and 6 months. The
      mean symptom severity and the number of symptoms at diagnosis were correlated
      with later ratings, but decreased in severity over time. A similar decrease in
      severity rating was seen for the individual symptoms in the cluster. The stage of
      cancer at diagnosis was the most predictive of the number of cluster symptoms
      reported. Death 6 to 19 months after diagnosis was predicted by age, stage of
      cancer at diagnosis, and symptom severity at 6 months. CONCLUSIONS: The symptom
      cluster remains over the course of lung cancer and is an independent predictor of
      the patient's death. Symptom severity, the number of symptoms reported, and the
      severity of the individual symptoms decreased over time. The stage of cancer at
      diagnosis is the best predictor of symptoms later in the disease.

PMID- 14639087
TI  - A systematically tested intervention for managing reactive depression.
AB  - BACKGROUND: Patients and family caregivers repeatedly experience reactive
      depression that leads to medication errors, mismanagement of chronic disease, and
      poor self-care. These problems place them at high-risk for malnutrition,
      infection, heart diseases, and psychiatric sequelae. OBJECTIVES: A secondary data
      analysis compared findings across a series of studies to evaluate the
      acceptability, effectiveness, and cost of a therapeutic writing intervention to
      reduce reactive depression, a common and frequently recurring adverse symptom.
      METHODS: Secondary analysis of data from the series of studies was conducted.
      Data came from patients requiring lifelong, daily central intravenous catheter
      infusion of home total parenteral nutrition necessitated by nonmalignant bowel
      disease and their family caregivers who assist with this complex home care.
      Variables combined across the studies were pre- and postintervention scores from
      the Center for Epidemiological Studies-Depression Scale (CES-D), the number of
      weeks patients wrote in their diaries (adherence), and the written content in the
      diaries. Content analysis was used to analyze written data. The intervention
      materials and nurses' time spent were averaged across studies to determine costs.
      RESULTS: The weighted average baseline CES-D scores across studies for patients
      (17.94) and caregivers (15.75) showed the presence of depression. After journal
      writing had been used for an average of 10.4 weeks across studies, the effect
      sizes of the between (d =.27) and within (d =.65) patient group scores indicated
      moderate to large improvement in depression. Themes from written diaries showed
      that missing out on activities, financial worries, strain related to the severe
      illness, and the complexity of home care were related to depression across the
      studies. CONCLUSIONS: The intervention was acceptable to participants, effective
      for managing reactive depression, and low in cost. The next steps will address
      testing for the longitudinal effects of the intervention.

PMID- 14639088
TI  - The notion of time in symptom experiences.
AB  - BACKGROUND: The experience of unpleasant sensations associated with the presence
      of symptoms prompts self-care or help seeking to obtain explanations for the
      symptoms, manage emotional responses, or obtain treatment for symptom alleviation
      and elimination. OBJECTIVE: The purpose of this article is to summarize and
      comment on three existing symptom theories, with special attention to temporal
      factors. METHODS: Existing theories are synthesized as the time dimensions of
      symptom experiences and symptom management processes are elucidated. Clinical
      examples and findings from empirical studies illustrate critical points.
      DISCUSSION: Existing theories describing the symptom experience and the process
      of symptom management refer implicitly to the role of time or use limited
      dimensions of time. Symptom experiences in time (SET) theory is proposed as a
      synthesis and extension of existing theories. The SET theory conceives the
      symptom experience as a flow process that explicitly incorporates temporal
      dimensions. Four dimensions of time are recognized: clock-calendar, biologic
      social, perceived, and transcendent time. The four temporal dimensions are placed
      against a backdrop of "meaning-in-time" that brings forth the potential for
      transformation in a symptom experience. Increasing sophistication in design,
      measurement, and data analysis is required to test and evaluate SET theory-based
      propositions. CONCLUSIONS: The SET theory extends previous work by incorporating
      multiple temporal dimensions that reflect the human experience of health and
      illness manifested in the expression and management of symptoms.

PMID- 14639089
TI  - Cellular mechanism for mibefradil-induced vasodilation of renal microcirculation:
      studies in the isolated perfused hydronephrotic kidney.
AB  - Although nifedipine and other conventional calcium antagonists elicit
      preferential vasodilation of renal afferent arterioles, we demonstrate that
      mibefradil and nickel, T-type calcium channel blockers, reverse the angiotensin
      II-induced constriction of both afferent and efferent arterioles. Since the
      angiotensin II-induced vasoconstriction involves inositol trisphosphate (IP3)
      induced calcium release from the sarcoplasmic reticulum in the afferent
      arteriole, and both IP3- and protein kinase C (PKC)-mediated pathways in the
      efferent arteriole, we investigated the cellular mechanism for the mibefradil
      induced dilation of angiotensin II-constricted renal arterioles, using the
      isolated perfused hydronephrotic rat kidney. Mibefradil caused a dose-dependent
      dilation of angiotensin II-constricted afferent and efferent arterioles, with 88
      +/- 9% and 74 +/- 10% reversal observed at 1 micromol/L, respectively. The
      blockade of PKC by staurosporine did not alter the mibefradil-induced vasodilator
      responses of either arterioles (P > 0.5). In contrast, the pretreatment with
      thapsigargin, which predominantly blocked the IP3-mediated intracellular calcium
      release, prevented the afferent arteriolar constrictor response to angiotensin
      II, but caused a significant constriction of efferent arterioles. The subsequent
      addition of mibefradil had no effect on the efferent arteriolar diameter.
      Furthermore, the efferent arteriolar constriction induced by direct PKC
      activation by phorbol myristate acetate was refractory to mibefradil, but
      completely reversed by LOE908, a nonselective cation channel blocker. In summary,
      mibefradil markedly dilates the angiotensin II-induced renal arteriolar
      constriction; the action of mibefradil is most likely mediated by the inhibition
      of the IP3-mediated pathway, but the inhibitory action on the PKC pathway appears
      modest.

PMID- 14639090
TI  - Endothelium-dependent, vasopressin-induced contractions in rabbit renal arteries.
AB  - OBJECTIVES: To identify and quantify the stimulatory and inhibitory activity of
      endothelial factors on Arginine vasopressin (AVP)-induced contractions. METHODS:
      In a standard organ bath set-up for isometric force recording, rabbit isolated
      renal artery rings were exposed to cumulative concentrations of AVP. Experiments
      were performed in the presence or absence of functional endothelium, or in the
      presence of N-Nitro-L-Arginine 10 microM (L-NNA) (NO-synthase inhibitor).
      RESULTS: Arginine vasopressin induced a maximal contractile response of 6.5 +/-
      0.1 mN in vessels with and 6.3 +/- 0.3 mN in vessels without endothelium. The
      preincubation with l-NNA resulted in an enhanced response to AVP of 12.6 +/- 0.8
      mN (P < 0.05). The augmentation of the AVP induced contractile response by NOS
      inhibition, which was not seen in preparations after the removal of the
      endothelium, suggests an endothelium dependent factor that is co-released with
      NO. The unknown nature of this endothelium dependent contractile factor was not
      influenced by indomethacin 100 microM (cyclooxygenase inhibitor), meclofenamic
      acid 20 microM (cyclooxygenase and lipoxygenase inhibitor), or bosentan 100
      microM (endothelin antagonist). Charybdotoxin 0.1 microM (inhibitor of Ca2+ 
      activated K+ channels) specifically increased the contractile force in
      preparations with and without endothelium, or in the presence of l-NNA to 11.2 +/
      0.4 mN, 14.0 +/- 0.8 mN, and 19.0 +/- 0.8 mN, respectively (P < 0.05 compared
      with the experiments without charybdotoxin). SR 49059 (vasopressin 1 receptor
      (V1) antagonist) antagonized the effects of AVP, whereas SR 121463 B (V2
      antagonist) was ineffective. In contrast to the results obtained with AVP,
      desmopressin (V2 agonist) showed no effect. CONCLUSION: The completely V1
      dependent AVP-induced contraction is partly inhibited by the stimulated release
      of NO. This was only demonstrable in endothelium intact vessels in the presence
      of l-NNA and not after removal of the endothelium. This strongly suggests the
      involvement of an unknown endothelium V1 receptor dependent contractile factor
      that is not influenced by inhibition of the prostaglandin, lipoxygenase, or
      endothelin pathway, or by blockade of the V2 receptor.

PMID- 14639091
TI  - Nitric oxide-dependent antiplatelet action of AT1-receptor antagonists in a
      pulmonary thromboembolism in mice.
AB  - The aim of this study was to determine whether AT1-receptor antagonists could
      inhibit platelet activation-dependent pulmonary thromboembolism in mice and to
      investigate the involvement of nitric oxide in this action. Losartan, its active
      metabolite EXP3174, and valsartan given intraperitoneally 1 hour before the
      thrombotic challenge (in doses of 3, 10, or 30 mg/kg) protected mice from death
      or hind-limb paralysis in response to intravenous injection of a mixture of
      collagen and epinephrine; losartan was effective in all doses used, whereas
      EXP3174 and valsartan reduced mortality only in the two higher doses. The
      protective action of EXP3174 and valsartan was abolished when nitric oxide
      synthase was inhibited with l-NAME, whereas that of losartan was only partially
      reduced. Moreover, only losartan protected mice from death caused by intravenous
      injection of the thromboxane A2 mimetic U46619 and this action was preserved in l
      NAME-pretreated animals. Our results demonstrate the ability of AT1-receptor
      antagonists to inhibit platelet activation in vivo in a nitric oxide-dependent
      mechanism. Stronger antiplatelet activity of losartan, most likely due to its
      blockade of thromboxane A2/prostaglandin H2 receptor, could be of potential
      clinical relevance, particularly in conditions in which synthesis of endogenous
      nitric oxide is impaired.

PMID- 14639092
TI  - Effect of angiotensin II receptor antagonism on cerebral vasomotor reserve in
      humans.
AB  - Angiotensin II receptor antagonists have been reported to modulate
      cerebrovascular flow in animals. We applied frequency-domain techniques to
      explore whether angiotensin II receptor activity plays a role in cerebrovascular
      dynamics in humans. Essential hypertensive patients with (AIIA, n = 10) and
      without (HT, n = 10) an angiotensin II receptor antagonist (Volsartane) and
      healthy with matched (CON, n = 10) and younger (YOUNG, n = 10) ages were
      enrolled. They underwent measurement of middle cerebral artery flow velocity
      (MCAFV) by transcranial Doppler ultrasound and noninvasive beat-to-beat arterial
      blood pressure (ABP). Fluctuations in ABP and MCAFV were diffracted into high
      frequency (HF, 0.15-0.4 Hz), low-frequency (LF, 0.04-0.15 Hz), and very low
      frequency (VLF, 0.016-0.04 Hz) components. The mean age did not statistically
      significantly differ among the CON, HT, and AIIA groups. HT had significantly
      higher mean ABP, lower LF fluctuations of ABP and MCAFV, but similar ABP-MCAFV
      transfer magnitude compared with CON. HF transfer magnitude of AIIA was
      significantly higher than those of HT and CON, but similar to that of YOUNG. We
      conclude that the elderly with chronic essential hypertension has a suppressive
      effect on cerebral vasomotor reserve, in which angiotensin II receptor activity
      may play an active role.

PMID- 14639093
TI  - Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone
      system in human primary hypertension: the Swedish Irbesartan Left Ventricular
      Hypertrophy Investigation versus Atenolol (SILVHIA).
AB  - We examined long-term influence of the angiotensin II type 1-receptor blocker
      irbesartan and the beta1-adrenergic receptor blocker atenolol on some
      neurohormonal systems implicated in the pathophysiology of cardiac hypertrophy.
      Thus, 115 hypertensive patients with left ventricular hypertrophy were randomized
      to receive double-blind irbesartan or atenolol, with additional therapy if
      needed. Neurohormone measurements and echocardiography were performed at weeks 0,
      12, 24, and 48. Left ventricular mass was reduced more by irbesartan than by
      atenolol (-26 g/m2 versus -14 g/m2, P = 0.024), despite similar reductions in
      blood pressure. Plasma renin activity and angiotensin II increased (P < 0.001) by
      irbesartan (0.9 +/- 0.7 to 3.4 +/- 4.2 ng/mL x h, and 3.0 +/- 1.6 to 13.0 +/-
      17.7 pmol/L), but decreased (P < 0.01) by atenolol (1.0 +/- 0.6 to 0.7 +/- 0.6
      ng/mL x h, and 3.4 +/- 1.6 to 3.2 +/- 2.2 pmol/L). Serum aldosterone decreased (P
      < 0.05) by both irbesartan (346 +/- 140 to 325 +/- 87 pmol/L) and atenolol (315
      +/- 115 to 283 +/- 77 pmol/L). Changes in left ventricular mass by irbesartan
      related inversely to changes in plasma renin activity, angiotensin II, and
      aldosterone (all P < 0.05). Plasma levels and 24-hour urinary excretions of
      catecholamines, plasma leptin, proinsulin, insulin and insulin sensitivity
      remained largely unchanged in both groups. Thus, the renin-angiotensin
      aldosterone system appears to be an important non-hemodynamic factor in the
      regulation of left ventricular mass.

PMID- 14639094
TI  - 3', 4'-dihydroxyflavonol enhances nitric oxide bioavailability and improves
      vascular function after ischemia and reperfusion injury in the rat.
AB  - We hypothesized that 3',4'-dihydroxyflavonol (DiOHF) by scavenging superoxide
      anions (O2-*) would increase the bioavailability of NO and potentiate NO-mediated
      relaxation in the rat aorta. Furthermore we hypothesized that DiOHF, by its
      antioxidant activity, would preserve responses to acetylcholine (ACh) in the
      presence of O2-* generators in the aorta in vitro and after ischemia and
      reperfusion of the rat hindquarters vasculature in situ. Using lucigenin-enhanced
      chemiluminescence we demonstrated that DiOHF caused a concentration-dependent
      reduction in O2-* accumulation whether generated by xanthine/xanthine oxidase in
      a cell-free system or by rat isolated aorta in the presence of NADPH. DiOHF also
      prevented the inhibitory effects of xanthine/xanthine oxidase and pyrogallol on
      vasorelaxation to ACh and sodium nitroprusside (SNP) in the rat aorta in vitro,
      and attenuated the vascular dysfunction caused by 2 h ischemia and 2 h
      reperfusion (I/R) in the rat hindquarters. I/R significantly reduced the dilator
      responses to both ACh and SNP; however, this effect was attenuated when DiOHF was
      given before the onset of ischemia or reperfusion. In conclusion, DiOHF, by
      scavenging O2-*, increases the relaxant activity of ACh and SNP and reduces the
      degree of inhibition of xanthine/xanthine oxidase or pyrogallol on the response
      to ACh. DiOHF reduces the adverse effects of I/R on vascular function by
      increasing NO bioavailability suggesting that it may be useful in preventing
      reperfusion injury.

PMID- 14639095
TI  - Modulation of A2A adenosine receptors and associated Galphas proteins by ZM
      241385 treatment of porcine coronary artery.
AB  - Functional regulation and expression of the adenosine A2A receptor and associated
      G-protein were investigated in porcine coronary artery exposed to an A2A receptor
      antagonist, ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3
      a][1,3,5]triazin-5-ylamino]ethyl)phenol). The arteries were incubated for 3 days
      in culture medium in the absence (control) and presence (treated) of 10 microM ZM
      241385. Changes in isometric tension by adenosine receptor agonists were
      evaluated in endothelium-free tissues. ZM 241385-treatment produced a
      statistically significant rightward displacement of CGS-21680, NECA, and CAD
      concentration-response curves compared with the respective controls (P < 0.05).
      The EC50, expressed in nM, values in treated and control tissues were: 617.3 +/-
      23 versus 24.9 +/- 1.5 for CGS-21680 (2-(p-(2-carboxyethyl)phenethylamino)-5'N
      ethylcarboxamidoadenosine), 27.4 +/- 6.3 versus 3.06 +/- 0.8 for NECA (5'-N
      ethylcarboxamidoadenosine), and 5786.2 +/- 160 versus 89.2 +/- 24.1 for CAD
      (chloroadenosine). However, the relaxing effect of forskolin remained unchanged
      in treated and control tissues. The concentration-response curves for NECA, CAD,
      and CGS-21680 were also displaced to the right when cAMP levels were measured in
      treated and control smooth muscle cells while no differences were observed with
      forskolin. Quantitative Western blot analysis demonstrated that the density of
      A2A receptors increased in ZM 241385-treated artery. We also showed a significant
      decrease in Galphas protein levels after ZM 241385 treatment compared with
      control. Taken together, these data indicate that prolonged blockade of A2A
      receptors in the coronary artery leads to desensitization of the functional
      effects of adenosine agonists by a mechanism that involves decreases in cAMP
      production. This was associated with an up-regulation of A2A receptors and a
      decrease in Galphas protein expression.

PMID- 14639096
TI  - L-ascorbic acid stimulates expression of smooth muscle-specific markers in smooth
      muscle cells both in vitro and in vivo.
AB  - The dedifferentiation of vascular smooth muscle cells (VSMCs) plays a critical
      role in the progression of atherosclerosis and restenosis after angioplasty.
      Thus, factors that stimulate smooth muscle cell differentiation should be useful
      for therapy for these diseases. Previously, we found that l-ascorbic acid (L-Asc)
      induces the expression of smooth muscle-specific genes in a pluripotent bone
      marrow stromal cell line, TBR-B. This finding suggests that l-Asc stimulates the
      differentiation of smooth muscle cells. In the present study, we investigated the
      effects of l-Asc and its derivatives on the differentiation state of VSMCs in
      vitro and in vivo. l-Asc and its long-lasting derivatives stimulated the
      production of smooth muscle-specific myosin heavy chain-1 (SM1) and calponin 1 in
      a dose-dependent manner in rat cultured VSMCs, and the elevated production of SM1
      and calponin 1 was maintained for at least 2 weeks. Moreover, oral administration
      of 3 g/kg of l-Asc to the balloon-injured rats induced a higher expression of SM1
      and calponin 1 in the injured arteries compared with that from administration of
      the delivery vehicle alone. These data demonstrated new biologic activity, such
      as the stimulation of VSMC differentiation, of l-Asc and its long-lasting
      derivatives. In addition, these compounds may serve as useful tools for analysis
      of the differentiation of VSMCs and for therapy for vascular diseases.

PMID- 14639097
TI  - Nephroprotective effect of bosentan in diabetic rats.
AB  - Previous studies have suggested that endothelins could be involved in the
      pathogenesis of target organ damage in diabetes. The aim of this study was to
      evaluate the possible protective effect of Bosentan, an antagonist of endothelin
      receptor, on the kidney of diabetic rats. The study comprised a control group of
      10 WKY rats and a group of 22 WKY rats in which diabetes was induced by
      streptozotocin i.v.; 10 rats were the control group. Diabetic rats received
      insulin and mean blood glucose was approximately mS 400 mg/dl throughout the
      study; they were divided into two groups: 11 rats received Bosentan 100 mg/kg/die
      by gastric gavage and 11 received vehicle for 1 month. Twenty-four hour urine
      collection was performed before and at the end of the study. Urinary protein
      excretion rate was expressed as microg urinary protein/mg urinary creatinine. The
      renal collagen I, fibronectin, and TGFbeta were evaluated by means of
      immunochemistry. The statistical analysis of the results demonstrates that
      Bosentan has prevented the increase in urinary protein excretion and that of
      renal immunoreactive collagen I, fibronectin, and TGFbeta induced by diabetes
      without reducing blood pressure. This study suggests a new clinical application
      for the antagonists of endothelin receptors.

PMID- 14639098
TI  - Role of adenosine and opioid-receptor mechanisms for pain in patients with silent
      myocardial ischemia or angina pectoris: a double-blind, placebo-controlled study.
AB  - Patients with silent myocardial ischemia have similar prognosis but fewer primary
      care and emergency care visits than patients with angina pectoris. Silent
      myocardial ischemia has been associated with an increased pain threshold because
      of an increased endogenous opioid receptor activity. In this double-blind,
      placebo-controlled study, we tested whether patients with silent myocardial
      ischemia would have less sensitivity to the ischemic pain messenger adenosine
      compared with angina pectoris patients and healthy controls. In addition, we
      tested whether this effect might be due to an increased opioid receptor activity.
      MATERIALS AND METHODS: Thirteen male patients with silent myocardial ischemia
      (mean age 58 +/- 10 years with BMI 25 +/- 3) were compared with 10 male patients
      with angina pectoris (mean age 57 +/- 9 years with BMI 29 +/- 5). Healthy
      volunteers (mean age 52 +/- 7 years with BMI 25 +/- 3, n = 10), acted as
      controls. Increasing doses of adenosine were injected rapidly into an
      antebrachial vein in a double-blind, randomized order. Central chest pain was
      provoked and quantified using psychophysical methods. The procedure was repeated
      after an injection of 0.4 mg of the non-selective opioid antagonist, naloxone.
      RESULTS: Patients with silent myocardial ischemia exhibited higher pain threshold
      than patients with angina pectoris and healthy volunteers. After naloxone,
      healthy volunteers and patients with angina pectoris tended to have more pain
      than patients with silent myocardial ischemia. CONCLUSION: In conclusion,
      patients with silent myocardial ischemia had a decreased sensitivity to adenosine
      provoked chest pain compared with patients with angina pectoris. The decreased
      pain sensitivity was not related to opioid receptor activity.

PMID- 14639099
TI  - CGX-1051, a peptide from Conus snail venom, attenuates infarction in rabbit
      hearts when administered at reperfusion.
AB  - CGX-1051, isolated from the venom of the marine snail Conus purpurasens, was
      previously noted to interact with potassium channels. Since potassium channels
      play an important role in cardiac physiology, we assessed the effect of CGX-1051
      on infarct size in a rabbit heart model of ischemia/reperfusion. A coronary
      branch was occluded for 30 minutes followed by 3 hours of reperfusion in in situ
      and 2 hours in in vitro preparations. Infarct size was measured with
      triphenyltetrazolium chloride staining and expressed as a percent of the risk
      zone. In in situ studies, a bolus intravenous injection of CGX-1051, either 10 or
      100 microg/kg, administered 5 minutes before reperfusion, reduced infarct size
      from 40.4 +/- 2.8% of the risk zone in untreated animals to 19.8 +/- 3.8% and
      15.0 +/- 1.9%, respectively. One microg/kg CGX-1051 was not protective. To see if
      the salvage was sustained, two groups of rabbits underwent 72 hours of
      reperfusion. The dose of 10 microg/kg infused 5 minutes before reperfusion
      reduced infarct size from 37.0 +/- 1.6% in untreated rabbits to 15.5 +/- 2.0%.
      When administered 10 minutes after reperfusion had begun, 100 microg/kg CGX-1051
      had no effect. CGX-1051 also reduced infarct size in crystalloid-perfused,
      isolated rabbit hearts suggesting that protection did not depend on circulating
      leukocytes. The mitochondrial KATP inhibitors glibenclamide and 5
      hydroxydecanoate and the MEK(1/2), ERK and hence, inhibitor PD 98059 aborted
      protection from CGX-1051. These data indicate that functionally active ERK and
      mitochondrial KATP channels are necessary for protection. CGX-1051 caused no
      hemodynamic alterations at any dose tested. We conclude that CGX-1051 has a
      powerful anti-infarct effect when given just before reperfusion.

PMID- 14639100
TI  - Blood pressure effects of intravenous apomorphine in conscious
      deoxycorticosterone-acetate salt-hypertensive rats.
AB  - SUMMARY: The present study reports the effects of apomorphine (APO) on blood
      pressure and the principal site of action of this agonist in 4-week
      deoxycorticosterone-acetate (DOCA)-hypertensive conscious rats. In these
      preprations, intravenous (i.v.) administration of APO (0.50-1 mg/kg) induced
      short-lasting and dose-dependent decreases in mean arterial pressure. The
      hypotensive response to APO (0.3 mg/kg) was reversed into a significant pressor
      effect by i.v. hexamethonium (30 mg/kg), whereas it was enhanced by i.v.
      pretreatment with the vasopressor antagonist of arginine vasopressin (AVP)
      d(CH2)5Tyr(Me)AVP (10 microg/kg) and/or prazosin (1 mg/kg). This depressor effect
      was suppressed by the central and peripheral dopamine D2 receptor antagonist
      metoclopramide (5 mg/kg i.v.), unaffected by the selective dopamine D1 receptor
      antagonist SCH 23390 (0.2 mg/kg i.v.), partly reduced by intrathecal domperidone
      (40 microg per rat at T9-T10 level), a dopamine D2 receptor antagonist which does
      not cross the blood-brain barrier, and reversed into a significant pressor effect
      by i.v. domperidone (0.5 mg/kg). The latter pressor effect was fully abolished by
      combined i.v. pretreatment with the vasopressor antagonist of AVP and prazosin.
      These results show that, in conscious DOCA salt-hypertensive rats, APO induced a
      brief, initial depressor effect, which is opposed to a central pressor component.
      The depressor component is related to an inhibition of norepinephrine
      transmission through activation of dopamine D2 receptors, some of which are
      located in the spinal cord and some of which are located in the peripheral
      circulation. The central pressor component, which became manifest after
      peripheral dopamine D2 receptor blockade, appears to be related to an increase in
      vasopressin release and sympathetic tone through activation of brain dopamine D2
      receptors.

PMID- 14639101
TI  - Proteomic studies of macrophage-derived foam cell from human U937 cell line using
      two-dimensional gel electrophoresis and tandem mass spectrometry.
AB  - SUMMARY: The authors have identified 37 proteins in the whole-cell extracts from
      human monoblastic leukemia (U937) cell and macrophage-derived foam cell. The in
      vitro foam cell model was established by incubating the human U937 cells with
      oxidized low-density lipoprotein. The global changes in protein expressions
      between U937 foam cell and normal U937 cells were measured with two-dimensional
      polyacrylamide gel electrophoresis, and some proteins were trypsin-digested and
      then identified through tandem mass spectrometry after capillary liquid
      chromatography separation. Some of the identified proteins were validated via
      Internet links to the U937 proteomic map provided on the Expasy proteomics
      server. The experimental data can provide potential markers for atherosclerotic
      studies.

PMID- 14639102
TI  - Protective effect of mitochondrial KATP activation in an isolated gracilis model
      of ischemia and reperfusion in dogs.
AB  - Adenosine triphosphate-sensitive potassium channel (KATP) openers protect
      ischemic myocardium by direct protection of cardiac myocytes, which is thought to
      be a result of activation of mitochondrial KATP (mKATP). KATP is expressed in
      skeletal muscle, and the purpose of this study was to determine the effect of the
      mKATP opener BMS-191095 on infarct size in an isolated gracilis model of ischemia
      and reperfusion in dogs. The right and left gracilis muscles were isolated in
      anesthetized dogs except for the artery and vein supplying these muscles
      (pedicle). BMS-191095 (0.4 mg) or vehicle were infused directly into the artery
      supplying each gracilis muscle (each animal had one drug-treated and one vehicle
      treated muscle). The pedicle was completely occluded for 5 hours followed by 48
      hours of reperfusion, after which infarct size was determined. In the vehicle
      treated gracilis muscles, significant necrosis was observed (82% +/- 3% of
      gracilis muscle). BMS-191095 significantly reduced the infarct size in the
      contralateral gracilis muscle (55% +/- 6%). Reflow into the gracilis muscle was
      significantly greater in BMS-191095-treated muscles. BMS-191095 appears to reduce
      damage in ischemic/reperfused skeletal muscle, suggesting that mKATP activation
      is an important protective mechanism in this tissue.

PMID- 14639103
TI  - DPC4/Smad4: no mutations, rare allelic imbalances, and retained protein
      expression in pancreatic endocrine tumors.
AB  - Several chromosomal loci involved in tumorigenesis of pancreatic endocrine tumors
      (PET) have been identified. To date, the only gene known to be frequently altered
      is the MEN1 gene. Recently, DPC4 mutations and homozygous deletions have been
      described in 5/9 (55%) non-functioning PET, thus representing the most frequent
      genetic aberration described in PET. However, these data are in discordance with
      comparative genomic hybridization (CGH) results that rarely show genetic losses
      on chromosome 18. They have also been challenged by immunohistochemical data. We
      performed a detailed combined DPC4 mutation and deletion analysis in 34 benign
      and malignant PET. Mutations of the conserved C-terminal exons were not found in
      all examined PET and allelic loss (LOH) was found to be rare (<6%) by combined
      microsatellite PCR and FISH analysis. In addition, DPC4 protein expression was
      retained in all PET that were examined by immunohistochemistry. Therefore, DPC4
      inactivation by mutation or deletion appears to be very rare in PET, which
      confirms the current concept of unrelated mechanisms of tumorigenesis of
      endocrine versus exocrine pancreatic tumors.

PMID- 14639104
TI  - Colon cancer-associated DNA mutations: marker selection for the detection of
      proximal colon cancer.
AB  - This study evaluates the potential ability of a specific panel of DNA mutations
      to identify right-sided colorectal carcinomas (CRCs) that would be missed by a
      flexible sigmoidoscopy (FS) screening program. This panel could then be applied
      to stool DNA analysis for noninvasive proximal CRC detection. A series of
      resected right-sided CRCs from 101 patients who had no left-sided advanced
      colonic neoplasms distal to the splenic flexure were analyzed. Tumor DNA was
      isolated from microdissected tumor sections. Deletions in the BAT-26 locus, a
      marker of microsatellite instability, and mutations at 19 loci spread among the
      p53, K-ras, and Apc genes were detected following PCR amplification. Mutations
      were identified in 83% of successfully amplified samples and were variably
      present in each of the target sites: p53 (42%), Apc (37%), K-ras (28%), and BAT
      26 (24%). Mutations were identified across all Dukes stages (CIS/A 6/8 [75%], B
      41/51[80%], C 30/32 (94%), and D 6/9 [67%]). Our data suggest that this 20-marker
      mutation panel may be associated with more than 80% of cancers undetectable by
      FS. The adjunctive use of stool DNA mutation analysis using this marker panel in
      FS CRC screening programs may significantly increase the detection of proximal
      CRC.

PMID- 14639105
TI  - Allelic loss of chromosome 6q in gastric carcinoma.
AB  - Loss of the long arm of chromosome 6 (6q) has frequently been reported in gastric
      carcinoma, and most gastric cancer patients have evidence of intestinal
      metaplasia in the stomach. However, the relationship between loss of chromosome
      6q and intestinal metaplasia has not been studied. In the first part of the
      study, we define the critical deletion region of chromosome 6q using loss of
      heterozygosity technique (LOH). Seventeen microsatellite markers were used to
      detect loss of heterozygosity (LOH) in 37 microdissected gastric tumors. We also
      examined intestinal metaplasia (IM) foci of the stomach in the same cancer
      patient (17 cases). Losses on chromosome 6q were detected in high frequency (51%)
      by LOH. Two distinct regions of common allelic loss were identified: one centered
      on the marker D6S300 (at 6q16.1) and the second on D6S446 (at 6q27), with LOH
      frequency of 36% and 31.3%, respectively. The deletions fall into 2 discrete
      regions, suggesting the existence of at least 2 tumor suppressor genes in 6q. The
      losses at 6q27 were confirmed by fluorescence in situ hybridization study (FISH).
      In the cases with LOH in the tumor, no LOH were detected in the autologous IM
      areas, but losses were detected by FISH. In some cases, these genetic changes may
      be acquired in the transition from normal gastric mucosa to intestinal
      metaplasia.

PMID- 14639106
TI  - HER-2/neu protein expression and gene alteration in stage I-IIIA non-small-cell
      lung cancer: a study of 140 cases using a combination of high throughput tissue
      microarray, immunohistochemistry, and fluorescent in situ hybridization.
AB  - Regarding HER-2/neu expression (gene or protein level) in lung cancer, several
      studies with inconsistent results have been recently reported, partially due to
      variable techniques used and/or heterogeneous populations examined. The objective
      of this study was to examine HER-2/neu expression in a well-defined cohort of non
      small-cell lung cancers (NSCLC) and in nonneoplastic lung tissue utilizing a
      combination of high-density tissue microarray, immunohistochemistry (IHC), and
      fluorescent in situ hybridization (FISH) under uniform test conditions. One
      hundred forty stage I-IIIA primary NSCLCs and 38 non-neoplastic lung samples were
      examined. IHC, using an FDA-approved Hercept monoclonal antibody kit, was
      performed and HER-2/neu gene alteration was assessed by FISH. The association of
      expression of HER-2/neu with clinicopathologic parameters was analyzed. Ninety
      four percent of tumor samples (131/140) were fully interpretable after tissue
      processing. Twenty-five of them (19%) overexpressed (2+, 3+) HER-2/neu, while 106
      (81%) had no or weak expression. All thirty-four interpretable non-neoplastic
      lung samples were negative for HER-2/neu alteration at protein and gene level.
      HER-2/neu protein overexpression correlated well with HER-2/neu gene
      amplification (r =.83, P < 0.001). HER-2/neu overexpression was significantly
      associated with histologic subtype: 19 adenocarcinomas (19/82, 23%) versus 4
      squamous cell carcinomas (4/44, 9%) overexpressed Her-2/neu (P = 0.04).
      Statistical significance was observed between HER-2/neu expression and tumor
      differentiation, with strong positive (3+) expression observed more frequently in
      poorly differentiated tumors (P = 0.01). Patients with HER-2/neu abnormalities,
      particularly HER-2/neu gene amplification, exhibited a shorter survival (P =
      0.043). The statistically significant difference (P < 0.005) between HER-2/neu
      alteration in tumor samples(25/131, 19%) and in the nonneoplastic tissue (0/34,
      0%) implies that HER-2/neu may have a role in the carcinogenesis of NSCLC. The
      findings provide evidence supporting the hypothesis that the HER-2/neu receptor
      may represent a useful molecular target in the treatment of NSCLC. The
      significant association of HER-2/neu expression and gene amplification with
      poorly differentiated carcinoma compared with well differentiated carcinoma
      suggests that HER-2/neu may be involved in NSCLC tumor evolution. Patients with
      HER-2/neu gene amplification and strong positive expression of HER-2/neu protein
      showed a strong tendency toward shorter survival.

PMID- 14639107
TI  - Clonality analysis of B-cell lymphoproliferative disorders using PCR and melting
      curve analysis.
AB  - Detection of a monoclonal immunoglobulin heavy chain gene (IgH gene)
      rearrangement is commonly used to support the diagnosis of B-cell non-Hodgkin
      lymphoma. We investigated the application of melting curve analysis as a
      substitute for polyacrylamide gel electrophoresis (PAGE) in the detection of
      monoclonal IgH gene rearrangements after PCR. A total of 140 cases were selected
      for this study, including 63 B-cell malignancies with a previously documented
      monoclonal IgH gene rearrangement. These 140 specimens were tested using PCR with
      melting curve analysis, and the results obtained were compared with PAGE results
      to calculate the relative sensitivity and specificity of melting curve analysis.
      Melting curve analysis detected monoclonal rearrangements in 56 of 63 specimens
      (relative sensitivity 88.9%). No false positives were detected (relative
      specificity = 100%). False-negative results were obtained only when a weak
      monoclonal band was present on PAGE. These results show that a positive result on
      melting curve analysis is specific for a monoclonal IgH gene rearrangement.
      However, with a sensitivity of only 88.9%, the majority of negative results would
      require further evaluation of the amplicons using PAGE. The application of
      melting curve analysis in the detection of monoclonal IgH gene rearrangements in
      the clinical laboratory setting is discussed.

PMID- 14639108
TI  - Detection of fusion gene transcripts in fresh-frozen and formalin-fixed paraffin
      embedded tissue sections of soft-tissue sarcomas after laser capture
      microdissection and rt-PCR.
AB  - The diagnosis of small round cell sarcomas is often very difficult, especially
      when only small biopsy specimens are available for examination. Recent studies
      have shown that some sarcomas have specific recurrent chromosomal translocations
      producing chimeric gene fusions, which can be detected by reverse transcription
      polymerase chain reaction (RT-PCR), fluorescent in situ hybridization (FISH), or
      cytogenetic analysis. In this study, 12 cases of well-defined sarcomas including
      Ewings sarcoma/primitive neuroectodermal tumors (ES/PNET), synovial sarcoma (SS),
      alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumors
      (DSRCT) were used to collect specific numbers of cells by laser capture
      microdissection (LCM), subsequently used for RT-PCR to detect specific chimeric
      gene transcripts. Tumor cells from fresh-frozen (FS) tissue sections and paraffin
      embedded (PS) tissue sections from the same cases were compared directly to
      evaluate the sensitivity of FS and PS sections as the starting material for
      analysis. Samples were used for RNA extraction, RT-PCR analysis, and Southern
      hybridization with fluorescein-labeled internal probes followed by enhance
      chemiluminescence (ECL) detection. The fusion gene transcripts could be detected
      using 50 cells from FS materials in all cases and from 1 cell in 9 of 12 cases.
      For PS, a positive signal could be detected using 200 to 1000 cells in all cases,
      while weaker signals were detected using 50 cells in most cases. These results
      indicate that the fusion gene products from small round cell sarcomas can be
      detected by RT-PCR with 10 to 200 cells from FS and PS tissues. The sensitivity
      of RT-PCR with FS was 10- to 50-fold greater than with PS. These results also
      suggest that RT-PCR analysis for sarcoma fusion gene products can be successfully
      performed when only a few cells are available for analysis, although this is not
      recommended for routine clinical use.

PMID- 14639109
TI  - Selection of higher molecular weight genomic DNA for molecular diagnosis from
      formalin-fixed material.
AB  - The patterns of DNA degradation in frozen, methanol-fixed, and formalin-fixed
      tissues were investigated by high-performance liquid chromatography (HPLC). The
      chromatograms all yielded one major peak with or without several extra minor
      peaks representing molecular weights of preserved genomic DNA. The most
      characteristic differences were in the retention times of the major peaks, with
      the earliest major peak occurring in the formalin-fixed tissues, and followed by
      the methanol-fixed, and frozen tissue samples, in that order. This means that the
      molecular weight of the DNA from formalin-fixed tissue is much shortened than
      that recovered from methanol-fixed tissue and frozen tissue. The results also
      indicated that a small amount of higher molecular weight DNA is still preserved
      in formalin-fixed tissues. To improve the amplification efficiency of polymerase
      chain reaction (PCR) analysis of formalin-fixed material, we isolated the higher
      molecular weight DNA from formalin-fixed, paraffin-embedded tissue from four
      different organs and compared the amplification efficiencies with those of the
      crude DNA extract. We used eight sets of oligonucleotide primers producing 262 to
      989 base pair (bp) fragments of beta-globin. The results showed that the PCR
      amplification analyses were more efficient with the isolated higher molecular
      weight DNA than with the crude DNA extract. Our study demonstrated that not all
      the DNA in formalin-fixed, paraffin-embedded tissue samples is totally degraded
      but that a small amount of higher molecular weight DNA persists. The feasibility
      of molecular diagnosis using formalin-fixed material can be improved by isolating
      the preserved higher molecular weight DNA by HPLC.

PMID- 14639110
TI  - MVarallo: a new M(Like) alpha 1-antitrypsin-deficient allele.
AB  - A 73-year-old never-smoker woman with chronic bronchitis, increasing dyspnoea,
      and airflow limitation with a FEV1 of 49% of predicted value had low serum level
      of alpha-1-antitrypsin (69 mg/dL, normal range 150-350). Isoelectric focusing
      showed an Mlike pattern. Direct sequencing showed, in the second exon, a
      particular DNA alteration localized between codon 41 and codon 51: a region of 30
      base pairs (bp) was completely deleted and substituted by a 22-bp sequence. The
      resulting loss of 8 bp yields, in the second exon, a 70-71 stop codon. This new
      Mlike variant was denominated MVarallo from the site where it was discovered.

PMID- 14639111
TI  - Taking the fear out of postanesthesia care in the intensive care unit.
AB  - This article was written for intensive care unit (ICU) nurses who find themselves
      having to recover surgical patients from anesthesia, whether they are critical
      care patients or acute care patients to be transferred to a regular nursing unit
      after recovery. Intensive care orientation programs may not adequately address
      the care of postanesthesia patients. This inadequacy manifests itself in the
      stress that intensive care nurses experience in caring for their patients. It may
      also present as a discomfort among anesthesia personnel with leaving a patient in
      the ICU postoperatively, and a lack of rapport between ICU nurses and anesthesia
      personnel. This article presents specific, practical information about nursing
      care of patients recovering from anesthesia, building on the existing assessment
      and interventional skills of the critical care nurse. It discusses the roles of
      the anesthesiologist, nurse anesthetist, and the postanesthesia care unit (PACU)
      nurse, and the types of anesthesia often seen in ICU recovery patients. It also
      covers preparation activities that can make the recovery process progress
      smoothly and offers tips and suggestions based on the author's experience related
      to special needs of postanesthesia patients that differ from the typical ICU
      patient.

PMID- 14639112
TI  - Guidelines for treating asthma.
AB  - Asthma is a chronic condition in which inflammatory changes occur in the airways
      characterized by mucosal inflation. While it is a chronic disease, it can be
      managed quite effectively in most patients. This article presents several of the
      new treatment guidelines for asthma.

PMID- 14639113
TI  - The latest in cardiac nursing.
AB  - Cardiovascular disease is still the leading cause of death in the United States,
      but the number of deaths is decreasing as new innovations in treatment are
      developed. Among the recent advances are coated stents, a second look at
      hypertension drugs, and new ways to assess risk and extent of coronary artery
      disease (CAD).

PMID- 14639114
TI  - The problem of plagiarism.
AB  - Unfortunately, the frequency of plagiarism is increasing in the nursing
      profession. We are encouraged to write, especially those of us in academia, and
      we all live very active lives. Pressure to publish, especially when coupled with
      lack of time, can lead to plagiarism, whether inadvertent or not. This article
      will discuss the problem of plagiarism and provide tips on how to avoid it in
      your own work.

PMID- 14639115
TI  - Nursing externship: a collaborative endeavor between nursing education and
      nursing administration.
AB  - This article provides an excellent description of an 8-week summer externship
      program for nursing students.

PMID- 14639117
TI  - Assessing pain control in nonverbal critically ill adults.
AB  - The accurate assessment of pain in nonverbal patients is difficult, with nurses
      often relying on a variety of methods to determine medication impact. Much of the
      evidence to date suggests that commonly used indicators of pain may not
      effectively measure the true extent of distress in patients unable to verbalize
      their level of discomfort. A recent pilot study of an existing and newly
      developed pain assessment scale reinforces this concern.

PMID- 14639118
TI  - The role of a research coordinator.

PMID- 14639121
TI  - Suppression of 7,12-dimethylbenz[alpha]anthracene-induced carcinogenesis and
      hypercholesterolaemia in rats by tocotrienol-rich fraction isolated from rice
      bran oil.
AB  - The anti-tumour and anti-cholesterol impacts of tocotrienol-rich fraction (TRF)
      were investigated in rats treated with the chemical carcinogen 7,12-dimethylbenz
      [alpha]anthracene (DMBA), which is known to induce mammary carcinogenesis and
      hypercholesterolaemia. DMBA administration to rats was associated with the
      appearance of multiple tumours on mammary glands after 6 months. Alkaline
      phosphatase (ALP) and glutathione-S-transferase (GST) are used as marker enzymes
      to monitor the severity of carcinogenesis. Although no tumours were visible on
      livers, hepatic ALP and GST activities of DMBA-treated rats were profoundly
      elevated in comparison to enzyme activities of normal control rats. Feeding of
      TRF (10 mg/kg body weight/day) for 6 months, isolated from rice bran oil (RBO),
      to DMBA-administered rats, reduced the severity and extent of neoplastic
      transformation in the mammary glands. Similarly, plasma and mammary ALP
      activities increased during carcinogenesis (95% and 43%, respectively), were
      significantly decreased in TRF-treated rats, whereas TRF mediated a further
      increase of 51% in hepatic ALP activity. TRF treatment to rats maintained low
      levels of GST activities in liver ( approximately 32%) and mammary glands (
      approximately 21%), which is consistent with anti-carcinogenic properties of TRF.
      Administration of DMBA also caused a significant increase of 30% in plasma total
      cholesterol and 111% in LDL-cholesterol levels compared with normal control
      levels. Feeding of TRF to rats caused a significant decline of 30% in total
      cholesterol and 67% in LDL-cholesterol levels compared with the DMBA-administered
      rats. The experimental hypercholesterolaemia caused a significant increase in
      enzymatic activity (23%) and protein mass (28%) of hepatic 3-hydroxy-3
      methylglutaryl co-enzyme A (HMG-CoA) reductase. Consistent with TRF-mediated
      reduction in plasma lipid levels, enzymatic activity and protein mass of HMG-CoA
      reductase was significantly reduced. These results indicate that TRF has potent
      anti-cancer and anti-cholesterol effects in rats.

PMID- 14639122
TI  - Lung cancer in North-West Italy: demographic and clinical trends in a hospital
      based population of 1277 patients.
AB  - This study intends to assess which demographic and/or clinical characteristics of
      lung cancer - if any - have changed during the last two decades in an Alpine area
      of North-West Italy. The study was carried out on 1277 consecutive lung cancer
      patients seen from January 1989 to October 2002 in a single institution. A set of
      33 anthropometric, clinical, physical, laboratory, radiological and pathological
      variables was prospectively recorded for all patients. The date of diagnosis was
      used to divide the study population in quartiles of diagnostic age (period I:
      January 1989 to May 1992, 319 patients; period II: June 1992 to September 1995,
      319 patients; period III: October 1995 to May 1999, 320 patients; period IV: June
      1999 to October 2002, 319 patients). Patients were carefully followed up, and
      their subsequent clinical course recorded. The following variables showed a
      significant increasing trend over the years: patients' age, female sex, rate of
      ex-smokers, level of education, co-morbidity (both the number and the severity of
      previous pulmonary and extrapulmonary diseases), weight loss, liver enzymes and
      blood creatinine, carcinoembryonic antigen levels and the rate of
      adenocarcinomas. On the other hand, performance status, stage of disease,
      metastatic pattern, treatment modalities and survival expectancy did not change.
      Therefore, no diagnostic or therapeutic improvements occurring during the last 14
      years had a visible impact on patients. It may be that the 'changing face' of
      lung cancer masked their effects.

PMID- 14639123
TI  - Antiproliferative effect of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on
      colonic epithelium of patients with adenomatous polyps in vitro.
AB  - We have consistently shown that the organoselenium compound 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) is a superior cancer chemopreventive
      agent and less toxic than selenite or certain naturally-occurring selenoamino
      acids. To elucidate the effects of p-XSC on human colonic mucosa, biopsies from
      endoscopically normal sigmoid colon of 30 patients with adenomatous polyps were
      incubated with p-XSC at concentrations of 1, 2 and 5 micromol/l dissolved in
      dimethylsulphoxide (DMSO). Biopsies incubated with DMSO or pure culture medium
      served as a control. Proliferating cells were labelled by bromodeoxyuridine
      immunohistochemistry and the labelling index (LI) was computed. Upper crypt
      labelling index (LI of crypt compartments 4+5) and Phih value, which are both
      discriminators of the expansion of the proliferative zone, were significantly
      lower after incubation with 1 and 5 micromol/l p-XSC, respectively (LI 4+5: 0.8
      and 1.0; Phih value: 2.1 and 2.4), as compared with DMSO (LI 4+5: 3.6 and 4.5;
      Phih value: 7.0 and 8.3) or culture medium (LI 4+5: 3.3 and 4.5; Phih value: 7.2
      and 8.1) (P<0.005 and P<0.05 by Friedman's block test). A trend towards lower
      levels of LI 4+5 (P=0.059) and Phih value (P=0.075) were seen after 2 micromol/l
      p-XSC incubation compared with DMSO. Since hyperproliferation of colonic crypt
      cells with expansion of the proliferative zone is regarded as a biomarker of
      increased cancer risk, the antiproliferative effects of p-XSC especially on upper
      crypt LI and Phih value may indicate a possible protective effect of this
      organoselenium compound in the prevention of human colon cancer development.

PMID- 14639124
TI  - The in vitro effects of H-89, a specific inhibitor of protein kinase A, in the
      human colonic carcinoma cell line Caco-2.
AB  - SUMMARY: H-89 is a compound characterized in vitro as a potent and selective
      inhibitor of protein kinase A. In the present study, we observed that H-89
      induced morphological transformation and caused growth inhibition of the human
      colon cancer cell line Caco-2 in a dose-dependent manner. However, another
      protein kinase A inhibitor, H-8, had no effect on Caco-2 cells. To evaluate the
      possible molecular mechanism of H-89-evoked effects in Caco-2 cells, we analysed
      the capacity of H-89 to regulate the protein kinase B (Akt/PKB) signalling
      pathway. H-89 treatment led to an activation of Akt/PKB in Caco-2 cells. This
      activation was phosphatidylinositol 3 (PI3)-kinase-dependent and promoted
      survival of Caco-2 cells because the PI3 kinase inhibitor LY294002 inhibited the
      Akt/PKB activation and induced apoptosis of Caco-2 cells. To test whether Akt/PKB
      activity promoted resistance to H-89-induced effects, LY294002 was added in
      combination with H-89. LY294002 greatly potentiated the H-89-induced growth
      inhibition and apoptosis of Caco-2 cells. These results suggest that the H-89
      induced growth inhibition of Caco-2 cells is associated with phosphorylation of
      Akt/PKB protein and that the cells become more sensitive to H-89 and die by
      apoptosis upon inhibition of the PI3K/Akt pathway.

PMID- 14639125
TI  - An earlier age of breast cancer diagnosis related to more frequent use of
      antiperspirants/deodorants and underarm shaving.
AB  - Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near
      the breast is the application of antiperspirants/deodorants accompanied by
      axillary shaving. A previous study did not support a link with breast cancer. If
      these habits have a role in breast cancer development, women using
      antiperspirants/deodorants and shaving their underarms frequently would be
      expected to have an earlier age of diagnosis than those doing so less often. An
      earlier age of diagnosis would also be expected in those starting to use
      deodorants and shaving at an earlier age. This is the first study to investigate
      the intensity of underarm exposure in a cohort of breast cancer survivors. Four
      hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once
      grouped by their frequency of underarm hygiene habits, the mean age of diagnosis
      was the primary end point. Secondary end points included the overall frequency of
      these habits, and potential usage group confounding variables were evaluated. All
      statistical tests were two-sided. Frequency and earlier onset of
      antiperspirant/deodorant usage with underarm shaving were associated with an
      earlier age of breast cancer diagnosis. Combined habits are likely for this
      earlier age of diagnosis. In conclusion, underarm shaving with
      antiperspirant/deodorant use may play a role in breast cancer. It is not clear
      which of these components are involved. Reviewed literature insinuates absorption
      of aluminium salts facilitated by dermal barrier disruption. Case-controlled
      investigations are needed before alternative underarm hygiene habits are
      suggested.

PMID- 14639126
TI  - Factors related to non-participation in a population-based breast cancer
      screening programme.
AB  - The main objectives were to describe the measures taken by women to detect breast
      disease prior to invitation to participate in a screening programme for breast
      cancer, and to identify factors related to non-participation in this programme. A
      cross-sectional study was designed at the Breast Cancer Early Detection Program
      of Sabadell-Cerdanyola (BCEDP), using data collected in interviews conducted face
      to face or over the telephone with 13 760 women participating in the programme
      and 280 non-participants. A total of 74.2% of the participants versus 70.4% of
      the non-participants reported having taken measures to detect breast disease, and
      71.7% of the participants had undergone mammography versus 69.6% of the non
      participants. Of the 10 057 women who had had mammograms, 58% had done so less
      than 2 years previously. Factors found to be associated to non-participation in
      the multivariate analysis were: higher level of education, higher occupational
      skills or working at home, self- or gynaecological examination of breasts, and
      having received hormone replacement therapy. Higher age group was the only factor
      that increased the probability of not having undergone mammography previously.
      Despite the high prevalence of prior measures to detect breast cancer and the
      similar prevalence between participating and non-participating women, this
      behaviour is much less prevalent in the group of women 60 years of age or older.

PMID- 14639127
TI  - CYP1A1 and XRCC1 gene polymorphisms in SCC of the larynx.
AB  - The present study was undertaken to examine CYP1A1 and XRCC1 polymorphisms as
      potential genetic susceptibility markers for laryngeal squamous cell carcinoma
      (SCC). Eighty-eight patients with laryngeal SCC and 178 randomly selected healthy
      blood donors from the same Caucasian population (Porto, Northern Portugal) were
      analysed for CYP1A1 (MspI and NcoI) and XRCC1 (Arg194Trp and Arg399Gln)
      polymorphisms, using PCR-RFLP techniques. CYP1A1 MspI MH (mutant homozygous) and
      CYP1A1 NcoI HT (heterozygous) genotypes were more frequent in patients than in
      controls, with those carrying a CYP1A1 NcoI HT genotype having a 2.3-fold higher
      risk for tumour development. On the other hand, polymorphisms in XRCC1 codon 399
      and codon 194 do not seem to play a role in the aetiology of smoking-related
      laryngeal SCC, once its distribution was similar in both analysed groups. All the
      significant associations observed were exclusively due to differences between
      controls and larynx glottic cancer patient subgroup. Furthermore, lower lifetime
      tobacco consumption was observed in laryngeal SCC patients carrying the MspI and
      NcoI polymorphisms, than in those who did not show the polymorphic variants. This
      investigation seems to support the importance of CYP1A1 gene polymorphism as a
      potential genetic marker of laryngeal cancer development, specially concerning
      smokers who have inherited the at-risk genotypes CYP1A1 MspI MH or CYP1A1 NcoI
      HT, who do appear to be more susceptible to the development of SCC of the glottic
      larynx.

PMID- 14639128
TI  - Transtheoretical model: investigation of adolescents' sunbathing behaviour.
AB  - The incidence of malignant melanoma and non-melanoma skin cancers has increased
      rapidly in Sweden as well as in other western countries during the last 20 years.
      Adolescents are an important group in skin cancer prevention. Interventions
      targeting this group have been reported to affect knowledge and attitudes, but
      the effect on sun protection behaviour has been slight. The aim of this study was
      to investigate the applicability of the Transtheoretical Model (TTM) for skin
      cancer prevention for adolescents. A random sample of 1200 18-year-olds living in
      Stockholm County was selected from the national census registry. A questionnaire
      that included three of the major constructs of the TTM (i.e. stages of change,
      processes of change and decisional balance) was sent by mail. The majority of the
      teenagers were in the precontemplation stage for giving up intentional tanning.
      The relations between the stages of change and two other major constructs of the
      TTM, processes of change and decisional balance, were consistent with data on
      other health behaviours. The results may aid in developing successful skin cancer
      prevention programmes. The results give support for the stages of change
      measurement used in this study and that utilizing the TTM in skin cancer
      prevention may be appropriate.

PMID- 14639129
TI  - Environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer: a
      systematic review of the epidemiological evidence.
AB  - Some PCB congeners have shown oestrogenic effects, and this has raised concern
      that they may increase the risk of breast cancer. In this article we provide a
      quantitative review of the epidemiologic evidence on environmental exposure to
      PCBs and breast cancer risk. The vast majority of prospective and retrospective
      studies did not find any association between total PCB concentrations and breast
      cancer risk. No association was found for congeners in groups I (potentially
      oestrogenic) and III (biologically persistent phenobarbital-type cytochrome P450
      inducers), according to the classification proposed by Wolff and Toniolo, while
      less consistent results were reported for group II (potentially anti-oestrogenic
      and immunotoxic, dioxin-like). Two studies found a threefold risk of
      postmenopausal breast cancer for women with an A2455G base change in exon 7 of
      the polymorphic CYP1A1 gene (a member of the cytochrome P450 family) and high PCB
      levels, compared with women with two wild-type alleles and low PCB, based however
      on very few cases. Thus, the epidemiological evidence does not support the
      hypothesis of an association of environmental exposure to PCBs in adulthood in
      the general population and risk of breast cancer, although uncertainties remain
      for selected subgroups of women or individual PCB congeners.

PMID- 14639130
TI  - Cancer risk among female nurses: a literature review.
AB  - Some studies have demonstrated increased risk of different cancers among female
      nurses. A review of relevant papers was made to assess whether the increase is
      caused by occupational exposures or other factors. A computerized literature
      search on combinations of the keywords 'nurses', 'occupation', 'hazards',
      'cancer' and 'mortality' and related articles was performed. A total of 30
      reports were identified from 19 independent studies conducted between 1983 and
      2001. The majority of the studies were registry studies, with limited data on
      employment history and confounding factors. In conclusion, knowledge about
      exposures and observed excesses of cancer risk give reason to suspect an
      occupational influence on breast cancer and leukaemia. The grouping together of
      nurses from different workplaces may camouflage real differences in risk. Future
      studies should collect information at the individual level about work history and
      personal risk factors.

PMID- 14639133
TI  - MAC Attack?

PMID- 14639134
TI  - Principles of successful sample surveys.

PMID- 14639135
TI  - Cardiac arrest following regional anesthesia with ropivacaine: here we go again!

PMID- 14639136
TI  - Reliability of pharmacodynamic analysis by logistic regression: mixed-effects
      modeling.
AB  - BACKGROUND: Many pharmacologic studies record data as binary, yes-or-no,
      variables with analysis using logistic regression. In a previous study, it was
      shown that estimates of C50, the drug concentration associated with a 50%
      probability of drug effect, were unbiased, whereas estimates of gamma, the term
      describing the steepness of the concentration-effect relationship, were biased
      when sparse data were naively pooled for analysis. In this study, it was
      determined whether mixed-effects analysis improved the accuracy of parameter
      estimation. METHODS: Pharmacodynamic studies with binary, yes-or-no, responses
      were simulated and analyzed with NONMEM. The bias and coefficient of variation of
      C50 and gamma estimates were determined as a function of numbers of patients in
      the simulated study, the number of simulated data points per patient, and the
      "true" value of gamma. In addition, 100 sparse binary human data sets were
      generated from an evaluation of midazolam for postoperative sedation of adult
      patients undergoing cardiac surgery by random selection of a single data point
      (sedation score vs. midazolam plasma concentration) from each of the 30 patients
      in the study. C50 and gamma were estimated for each of these data sets by using
      NONMEM and were compared with the estimates from the complete data set of 656
      observations. RESULTS: Estimates of C50 were unbiased, even for sparse data (one
      data point per patient) with coefficients of variation of 30-50%. Estimates of
      gamma were highly biased for sparse data for all values of gamma greater than 1,
      and the value of gamma was overestimated. Unbiased estimation of gamma required
      10 data points per patient. The coefficient of variation of gamma estimates was
      greater than that of the C50 estimates. Clinical data for sedation with midazolam
      confirmed the simulation results, showing an overestimate of gamma with sparse
      data. CONCLUSION: Although accurate estimations of C50 from sparse binary data
      are possible, estimates of gamma are biased. Data with 10 or more observations
      per patient is necessary for accurate estimations of gamma.

PMID- 14639137
TI  - Epsilon-aminocaproic acid in coronary artery bypass graft surgery: preincision or
      postheparin?
AB  - BACKGROUND: Epsilon-aminocaproic acid (epsilon-ACA), an antifibrinolytic agent,
      is used in cardiac surgery to decrease postoperative bleeding. Theoretical
      concerns exist about the potential for epsilon-ACA to contribute to thrombotic
      complications. For this reason epsilon-ACA administration is sometimes delayed
      until after heparinization. This study investigated the impact of the timing of
      epsilon-ACA administration on its efficacy. METHODS: In this double-blind study,
      90 patients undergoing primary coronary artery bypass graft surgery were
      prospectively randomized to receive either epsilon-ACA commencing prior to skin
      incision (bolus 150 mg/kg, followed by an infusion at 15 mg x kg(-1) x hr(-1),
      epsilon-ACA commencing after heparin (same doses), or placebo. All infusions were
      terminated at the end of cardiopulmonary bypass. Criteria for the transfusion of
      blood products were standardized. Postoperative chest tube drainage (at 6 h, 12
      h, and at chest tube removal) and blood transfusion requirements of the three
      groups were compared. RESULTS: At all time intervals, the placebo group had
      significantly greater chest tube drainage than either of the two epsilon-ACA
      groups (P < 0.005). At no time did a significant difference exist between the two
      epsilon-ACA groups. A trend existed for the placebo group to require more blood
      products than either epsilon-ACA group. CONCLUSIONS: Epsilon-ACA produces a
      reduction in chest tube drainage in patients undergoing primary coronary artery
      bypass graft surgery. This effect is similar whether the drug is given prior to
      incision or following anticoagulation. Given the similar hemostatic efficacy and
      the theoretical potential for thrombotic complications, it may be prudent to
      administer epsilon-ACA following anticoagulation.

PMID- 14639138
TI  - Reliability and validity of a simulation-based acute care skills assessment for
      medical students and residents.
AB  - BACKGROUND: Medical students and residents are expected to be able to manage a
      variety of critical events after training, but many of these individuals have
      limited clinical experiences in the diagnosis and treatment of these conditions.
      Life-sized mannequins that model critical events can be used to evaluate the
      skills required to manage and treat acute medical conditions. The purpose of this
      study was to develop and test simulation exercises and associated scoring methods
      that could be used to evaluate the acute care skills of final-year medical
      students and first-year residents. METHODS: The authors developed and tested 10
      simulated acute care situations that clinical faculty at a major medical school
      expects graduating physicians to be able to recognize and treat at the conclusion
      of training. Forty medical students and residents participated in the evaluation
      of the exercises. Four faculty members scored the students/residents. RESULTS:
      The reliability of the simulation scores was moderate and was most strongly
      influenced by the choice and number of simulated encounters. The validity of the
      simulation scores was supported through comparisons of students'/residents'
      performances in relation to their clinical backgrounds and experience.
      CONCLUSION: Acute care skills can be validly and reliably measured using a
      simulation technology. However, multiple simulated encounters, covering a broad
      domain, are needed to effectively and accurately estimate student/resident
      abilities in acute care settings.

PMID- 14639139
TI  - Mechanism of pupillary reflex dilation in awake volunteers and in organ donors.
AB  - BACKGROUND: The mechanism of reflex pupillary dilation was investigated in eight
      patients who were declared brain dead after rupture of intracranial vascular
      malformations and in eight awake volunteers. The authors hypothesized that the
      reflex was primarily a spinal sympathetic reflex that would be blocked by topical
      application of the alpha1-adrenergic blocking agent dapiprazole and that it would
      be present in organ donors with intact spinal reflexes and no history of hypoxia.
      METHODS: In volunteers, pupil size was measured with an infrared pupillometer
      while brief painful electric stimuli were delivered to the finger. Pain was
      assessed with a visual analog scale and adjusted with each volunteer to equal 3
      on a visual analog scale of 0-10. Subjects were studied before and after topical
      application of the alpha1-adrenergic antagonist dapiprazole. In organ donors, the
      authors measured pupil size after high-intensity tetanic electric stimulation and
      in dapiprazole-blocked and -unblocked pupils after surgically induced
      nociception. RESULTS: In volunteers, the pupil dilated 0.43 +/- 0.23 mm after
      nociceptive stimuli. Dapiprazole eyedrops blocked this dilation, confirming that
      the reflex in awake humans is primarily a sympathetic reflex. Baseline diameters
      were 5.7 +/- 0.5 mm before dapiprazole and 4.1 +/- 0.9 mm after dapiprazole. In
      organ donors, a tetanic electric current failed to dilate the pupil, whereas the
      skin incision dilated the pupil 0.4 +/- 0.4 mm, but this dilation was not blocked
      by dapiprazole. CONCLUSION: The authors conclude that pupillary reflex dilation,
      as it is clinically performed in awake subjects by stimulating somatic
      nociceptors, is a sympathetic reflex. Because it is not present in organ donors,
      the neural pathway must require a supraspinal component for completion.

PMID- 14639140
TI  - Tissue factor and platelet glycoprotein Ib-alpha alleles are associated with age
      at first coronary bypass operation.
AB  - BACKGROUND: Age is a known risk factor for postoperative complications, but the
      genetic factors that account for variability in age at presentation for surgery
      have not been characterized. Because thrombosis is a critical process in the
      development of coronary syndromes, the authors hypothesized that patients bearing
      the -1208 insertion allele of tissue factor (TF) and longer glycoprotein Ib-alpha
      (GpIbalpha) variants may come to surgical attention sooner and undergo coronary
      artery bypass grafting (CABG) at a younger age. The authors tested this
      hypothesis in a cardiac surgery population. METHODS: The impact of the number of
      TF -1208 insertion alleles and the number of GpIbalpha repeats on age at first
      CABG were tested in 424 elective coronary bypass patients. Multivariate
      regression included traditional risk factors of sex, hypertension, diabetes,
      hyperlipidemia, and smoking. The authors also tested the hypothesis that these
      alleles are correlated with age at first noncoronary cardiac surgery in a group
      of 143 patients undergoing noncoronary cardiac operations. RESULT: Both the
      number of TF -1208 insertion alleles and total number of GpIbalpha repeats were
      associated with younger age at first CABG in a univariate analysis. In
      multivariate regression in which traditional risk factors were included, the
      number of TF -1208 insertion alleles and the total number of GpIbalpha repeats
      were independent contributors toward age at first CABG. Neither polymorphism had
      a significant impact on age at first noncoronary cardiac surgery. CONCLUSIONS:
      Genetic variants in TF and GpIbalpha are associated with younger age at first
      CABG, indicating that the younger and older first-time CABG populations are
      different on the genetic level. How these genetic differences may account for age
      associated differences in perioperative risk will be the subject of future
      investigations.

PMID- 14639141
TI  - Sleep arousal after lower abdominal surgery and relation to recovery from
      respiratory obstruction.
AB  - BACKGROUND: Hypoxemic episodes occur during sleep after abdominal surgery,
      possibly caused by airway obstruction. The authors found arousals from sleep more
      often than respiratory disturbances, so they related changes in sleep state
      (short arousals from sleep and longer periods of wakening) to the sudden increase
      in respiratory flow that indicates relief from complete or partial respiratory
      obstruction. METHODS: Sleep state and nasal flow were studied in 16 patients
      receiving patient-controlled morphine and oxygen by facemask on the night after
      routine gynecologic surgery. Traces were analyzed separately for sleep events and
      for sudden increases in respiratory flow. The authors noted sleep events
      (arousals from sleep and transition from sleep to wake) that occurred within 12 s
      of relief of obstruction. RESULTS: Sleep quality was poor, with only stage 2
      sleep in most patients. Median sleep duration was 70% of the study period, with
      15 arousals and 6 awakenings per hour of sleep. Only 30% of arousals and
      awakenings were associated with relief of obstruction. Relief of obstruction also
      occurred without arousal from sleep, with a median frequency of 38 (30-62) in
      each night. Relief of obstruction was more frequently associated with arousal
      from sleep after benzodiazepine premedication (33% vs. 28%; P = 0.012), but this
      allocation was not randomized. CONCLUSIONS: Arousals from sleep are frequent
      after abdominal surgery and mostly not related to respiratory disturbance. Relief
      of respiratory obstruction can occur during sleep without sleep arousal and
      during wakefulness.

PMID- 14639142
TI  - Halothane enhances gamma-aminobutyric acid receptor type A function but does not
      change overall inhibition in inspiratory premotor neurons in a decerebrate dog
      model.
AB  - BACKGROUND: Inspiratory premotor neurons in the caudal ventral medulla relay
      excitatory drive to phrenic and inspiratory intercostal motoneurons in the spinal
      cord. These neurons are subject to tonic gamma-aminobutyric acid type A (GABA(A))
      mediated (GABA(A)ergic) inhibition. In a previous study, 1 minimum alveolar
      concentration (MAC) halothane depressed overall glutamatergic excitatory drive
      but did not change overall inhibitory drive to the neurons. This study
      investigated in further detail the effects of halothane on GABA(A)ergic
      inhibition by examining postsynaptic GABA(A) receptor activity in these neurons.
      METHODS: Studies were performed in decerebrate, vagotomized, paralyzed, and
      mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 MAC
      halothane on extracellularly recorded neuronal activity was measured during
      localized picoejection of the GABA(A) receptor antagonist bicuculline and the
      GABA(A) agonist muscimol. Complete blockade of GABAergic inhibition by
      bicuculline allowed estimation of the prevailing overall inhibition of the
      neuron. The neuronal response to muscimol was used to assess the anesthetic
      effect on the postsynaptic GABA(A) receptor function. RESULTS: One minimum
      alveolar concentration halothane depressed the spontaneous activity of 19
      inspiratory premotor neurons by 22.9 +/- 29.1% (mean +/- SD; P < 0.01). Overall
      excitatory drive was depressed 23.6 +/- 16.9% (P < 0.001). Overall GABAergic
      inhibition was not changed (+8.7 +/- 27.5%; P = 0.295), but the postsynaptic
      GABA(A) receptor function was increased by 110.3 +/- 97.5% (P < 0.001).
      CONCLUSION: One minimum alveolar concentration halothane greatly enhanced GABA(A)
      receptor function on inspiratory premotor neurons but did not change overall
      synaptic inhibition, indicating that the presynaptic inhibitory input was
      reduced. Therefore, the anesthetic depression of spontaneous inspiratory premotor
      neuronal activity in the intact brainstem respiratory network is mainly due to a
      decrease in overall glutamatergic excitation.

PMID- 14639143
TI  - Setting mean airway pressure during high-frequency oscillatory ventilation
      according to the static pressure--volume curve in surfactant-deficient lung
      injury: a computed tomography study.
AB  - BACKGROUND: Numerous studies suggest setting positive end-expiratory pressure
      during conventional ventilation according to the static pressure-volume (P-V)
      curve, whereas data on how to adjust mean airway pressure (P(aw)) during high
      frequency oscillatory ventilation (HFOV) are still scarce. The aims of the
      current study were to (1) examine the respiratory and hemodynamic effects of
      setting P(aw) during HFOV according to the static P-V curve, (2) assess the
      effect of increasing and decreasing P(aw) on slice volumes and aeration patterns
      at the lung apex and base using computed tomography, and (3) study the
      suitability of the P-V curve to set P(aw) by comparing computed tomography
      findings during HFOV with those obtained during recording of the static P-V curve
      at comparable pressures. METHODS: Saline lung lavage was performed in seven adult
      pigs. P-V curves were obtained with computed tomography scanning at each volume
      step at the lung apex and base. The lower inflection point (Pflex) was
      determined, and HFOV was started with P(aw) set at Pflex. The pigs were provided
      five 1-h cycles of HFOV. P(aw), first set at Pflex, was increased to 1.5 times
      Pflex (termed 1.5 Pflex(inc)) and 2 Pflex and decreased thereafter to 1.5 times
      Pflex and Pflex (termed 1.5 Pflex(dec) and Pflex(dec)). Hourly measurements of
      respiratory and hemodynamic variables as well as computed tomography scans at the
      apex and base were made. RESULTS: High-frequency oscillatory ventilation at a
      P(aw) of 1.5 Pflex(inc) reestablished preinjury arterial oxygen tension values.
      Further increase in P(aw) did not change oxygenation, but it decreased oxygen
      delivery as a result of decreased cardiac output. No differences in respiratory
      or hemodynamic variables were observed when comparing HFOV at corresponding P(aw)
      during increasing and decreasing P(aw). Variation in total slice lung volume
      (TLVs) was far less than expected from the static P-V curve. Overdistended lung
      volume was constant and less than 3% of TLVs. TLVs values during HFOV at Pflex,
      1.5 Pflex(inc), and 2 Pflex were significantly greater than TLVs values at
      corresponding tracheal pressures on the inflation limb of the static P-V curve
      and located near the deflation limb. In contrast, TLVs values during HFOV at
      decreasing P(aw) (i.e., 1.5 Pflex(dec) and Pflex(dec)) were not significantly
      greater than corresponding TLV on the deflation limb of the static P-V curves.
      The marked hysteresis observed during static P-V curve recordings was absent
      during HFOV. CONCLUSIONS: High-frequency oscillatory ventilation using P(aw) set
      according to a static P-V curve results in effective lung recruitment, and slice
      lung volumes during HFOV are equal to those from the deflation limb of the static
      P-V curve at equivalent pressures.

PMID- 14639144
TI  - Acid-induced lung injury: role of nuclear factor-kappaB.
AB  - BACKGROUND: Aspiration of acidic gastric contents leads to acute lung injury and
      is still one of the most common clinical events associated with acute lung
      injury. This study was performed to assess acid-induced lung inflammation in
      vitro and in vivo with respect to the time pattern of activated transcription
      factor nuclear factor-kappaB (NF-kappaB) and proinflammatory molecules. METHODS:
      L2 cells (alveolar epithelial cells) were exposed for various periods to a medium
      with a pH of 6. In the in vivo model, 1 ml/kg of 0.1 n acidic solution was
      instilled into the lungs of rats. NF-kappaB binding activity and expression
      pattern of inflammatory mediators were determined. Blocking studies were
      performed with the NF-kappaB inhibitor pyrrolidine dithiocarbamate. RESULTS: In
      vitro NF-kappaB binding activity showed a biphasic expression pattern with a
      first peak at 1 h and a second one at 6-8 h. In acid-injured rat lungs, NF-kappaB
      binding activity was confirmed in a biphasic manner with a first increase at 0.5
      2 h (608 +/- 93% and 500 +/- 15%, respectively, P < 0.05) and a second peak at 8
      h (697 +/- 35% increase, P < 0.005). Whole lung mRNA for macrophage inflammatory
      protein-1beta and macrophage inflammatory protein-2 showed a similar expression
      pattern, which could explain the biphasic neutrophil recruitment. Intratracheal
      pyrrolidine dithiocarbamate attenuated lung injury as evidenced by a reduction of
      neutrophil accumulation and expression of inflammatory mediators. CONCLUSIONS:
      These data suggest that NF-kappaB binding activity plays a key role in molecular
      and cellular events in acid-induced lung injury.

PMID- 14639145
TI  - Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K+
      channels in parenchymal microvessels of the rat cerebral cortex.
AB  - BACKGROUND: Carbon dioxide is an important vasodilator of cerebral blood vessels.
      Cerebral vasodilation mediated by adenosine triphosphate (ATP)-sensitive K+
      channels has not been demonstrated in precapillary microvessel levels. Therefore,
      the current study was designed to examine whether ATP-sensitive K+ channels play
      a role in vasodilation induced by mild hypercapnia in precapillary arterioles of
      the rat cerebral cortex. METHODS: Brain slices from rat cerebral cortex were
      prepared and superfused with artificial cerebrospinal fluid, including normal
      (Pco2 = 40 mmHg; pH = 7.4), hypercapnic (Pco2 = 50 mmHg; pH = 7.3), and
      hypercapnic normal pH (Pco2 = 50 mmHg; pH = 7.4) solutions. The ID of a cerebral
      parenchymal arteriole (5-9.5 microm) was monitored using computerized
      videomicroscopy. RESULTS: During contraction to prostaglandin F2alpha (5 x 10(-7)
      m), hypercapnia, but not hypercapnia under normal pH, induced marked
      vasodilation, which was completely abolished by the selective ATP-sensitive K+
      channel antagonist glibenclamide (5 x 10(-6) m). However, the selective Ca2+
      dependent K+ channel antagonist iberiotoxin (10(-7) m) as well as the nitric
      oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10(-4) m) did not
      alter vasodilation. A selective ATP-sensitive K+ channel opener, levcromakalim (3
      x 10(-8) to 3 x 10(-7) m), induced vasodilation, whereas this vasodilation was
      abolished by glibenclamide. CONCLUSION: These results suggest that in parenchymal
      microvessels of the rat cerebral cortex, decreased pH corresponding with
      hypercapnia, but not hypercapnia itself, contributes to cerebral vasodilation
      produced by carbon dioxide and that ATP-sensitive K+ channels play a major role
      in vasodilator responses produced by mild hypercapnia.

PMID- 14639146
TI  - Halothane inhibits an intermediate conductance Ca2+-activated K+ channel by
      acting at the extracellular side of the ionic pore.
AB  - BACKGROUND: Actions of volatile anesthetics on ligand-gated ion channels, such as
      gamma-aminobutyric acid type A receptors, have been studied extensively. However,
      actions on other types of channels, such as K+ channels, are poorly understood.
      The authors previously showed that a Ca2+-activated K+ channel, IK, is sensitive
      to halothane, whereas SK1, another Ca2+-activated K+ channel, is insensitive. To
      explore how halothane acts on Ca2+-activated K+ channels, chimeras between IK and
      SK1 were constructed, and halothane sensitivity was analyzed. METHODS: IK, SK1,
      and chimera channels were expressed in Xenopus laevis oocytes. Currents of
      expressed channels were measured in the presence of 10 microm Ca2+ by excised
      patch clamp analysis. Time constants of inhibition by halothane were compared
      between inside-out and outside-out patch configurations. RESULTS: Currents from
      chimera channels possessing the pore domain derived from IK were inhibited by
      halothane, whereas those possessing the SK1 pore domain were insensitive. Time
      constants of inhibition by halothane were significantly smaller in the outside
      out patches than in the inside-out patches of both wild-type IK and a chimera
      with pore domain of IK. CONCLUSIONS: It is suggested that halothane interacts
      with the extracellular part of the ionic pore of IK. Whether this type of
      interaction is involved in the mechanism of anesthetic actions on ligand-gated
      ion channels warrants further investigation.

PMID- 14639147
TI  - Isoflurane enhances the expression and activity of glutamate transporter type 3
      in C6 glioma cells.
AB  - BACKGROUND: Glutamate transporters play an important role in maintaining
      extracellular glutamate homeostasis. Volatile anesthetics have been shown to
      affect glutamate transporter activity acutely (within minutes after the
      exposure). It is not known whether volatile anesthetics affect the expression of
      glutamate transporters. METHODS: Rat cultured C6 glioma cells that express
      excitatory amino acid transporter type 3 (EAAT3) were exposed to isoflurane at
      various concentrations (0.5-4.0%) or for different periods (1-24 h) at 37 degrees
      C. EAAT3 mRNA, proteins, and activity were quantified. RESULTS: Isoflurane
      induced a time- and concentration-dependent increase in the mRNA and protein
      levels of EAAT3 in C6 cells. The maximal increase was induced by 2% isoflurane,
      and the cells incubated with 2% isoflurane for 3 and 7 h expressed the highest
      levels of EAAT3 mRNA and proteins, respectively. Similarly, glutamate uptake was
      higher in C6 cells exposed to 2% isoflurane for 7 h than in control cells.
      Actinomycin D and cycloheximide, inhibitors for mRNA and protein synthesis,
      respectively, did not affect the isoflurane-induced increase in EAAT3 mRNA and
      protein expression. Phorbol 12-myristate 13-acetate, a protein kinase C
      activator, also enhanced EAAT3 expression. The combination of 2% isoflurane and
      phorbol 12-myristate 13-acetate caused a higher level of EAAT3 expression than
      that induced by 2% isoflurane alone. Neither staurosporine, a protein kinase C
      inhibitor, nor wortmannin, a phosphatidylinositol 3 kinase inhibitor, inhibited
      the isoflurane-induced increase in EAAT3 expression. CONCLUSIONS: The results of
      this study suggest that isoflurane increases the expression and activity of EAAT3
      by stabilizing EAAT3 mRNA and proteins via protein kinase C- and
      phosphatidylinositol 3 kinase-independent pathways.

PMID- 14639148
TI  - Relative analgesic potencies of levobupivacaine and ropivacaine for epidural
      analgesia in labor.
AB  - BACKGROUND: The minimum local analgesic concentration has been defined as the
      median effective local analgesic concentration (EC50) in a 20-ml volume for
      epidural analgesia in the first stage of labor. The aim of this study was to
      assess the relative analgesic potencies of epidural levobupivacaine and
      ropivacaine by determination of their respective minimum local analgesic
      concentrations. METHODS: Parturients at 7 cm of cervical dilation or less who
      requested epidural analgesia were allocated to one of two groups in this double
      blind, randomized, prospective study. After lumbar epidural catheter placement,
      20 ml of the test solution was given: levobupivacaine (n = 35) or ropivacaine (n
      = 35). The concentration of local anesthetic was determined by the response of
      the previous patient in that group to a higher or lower concentration using up
      down sequential allocation. Analgesic efficacy was assessed using 100-mm visual
      analog pain scale scores, with 10 mm or less within 30 min defined as effective.
      An effective result directed a 0.01% wt/vol decrement for the next patient. An
      ineffective result directed a 0.01% wt/vol increment. RESULTS: Of 105 women
      enrolled, 35 were excluded, leaving 70 for analysis. The minimum local analgesic
      concentration of levobupivacaine was 0.087% wt/vol (95% CI, 0.081-0.094%), and
      the minimum local analgesic concentration of ropivacaine was 0.089% wt/vol (95%
      CI, 0.075-0.103%). Levobupivacaine and ropivacaine were of similar potency with a
      ropivacaine:levobupivacaine potency ratio of 0.98 (95% CI, 0.80-1.20). No
      difference in motor effects was observed. CONCLUSIONS: This study demonstrated
      that levobupivacaine and ropivacaine are of similar potency for epidural
      analgesia in the first stage of labor.

PMID- 14639149
TI  - Influence of age and sex on the position of the conus medullaris and Tuffier's
      line in adults.
AB  - BACKGROUND: The purpose of this study was to analyze the position of the conus
      medullaris and Tuffier's line in the same patient population, to correlate this
      position with age and sex, and to determine an objective guide for the selection
      of a safe intervertebral space during spinal block. METHODS: Magnetic resonance
      imaging studies of the lumbar spine were reviewed in 690 consecutive patients.
      The study population consisted of patients older than 20 yr who had been referred
      for imaging to assess possible causes of low back pain. The position of the conus
      medullaris was defined as the most distal point of the cord that could be
      visualized on the sagittal sequence. A line perpendicular to the long axis of the
      cord was extended to the adjacent vertebra. In the lumbar plain films, the
      Tuffier's line was defined by drawing a horizontal line across the highest points
      of the iliac crests. Each vertebral body and intervertebral space was divided
      into four segments: upper, middle, and lower thirds of a vertebral body, and the
      intervertebral space. Each segment of a vertebral body or intervertebral space
      that the lines crossed was identified and recorded. The positions, stratified by
      decade of age, were compared using analysis of variance. The Tukey test was used
      for post hoc comparisons. Comparisons between sex were performed with the
      unpaired t test. RESULTS: The conus medullaris and Tuffier's line (median
      [range]) were positioned at L1-lower (T12-upper-L3-upper) and L4L5 (L3L4-L5S1),
      respectively. The distance between the conus medullaris and Tuffier's line (mean
      +/- SD [range]) was 12.6 +/- 1.9 [7-18] segments, which corresponded to the
      height of approximately three vertebral bodies and intervertebral spaces. In no
      case did Tuffier's line overlap with the conus medullaris. The distance in
      segments between the conus medullaris and Tuffier's line was shorter with
      increased age (P < 0.001). The position of the conus medullaris and Tuffier's
      line was lower in female patients than in male patients (P < 0.001) and higher in
      patients with sacralization than in those with lumbarization or without
      transitional vertebra (P < 0.001). The in-between distances were not
      significantly different regardless of sex or presence of transitional vertebra.
      CONCLUSIONS: During spinal block, there seems to be a safety margin of 2-4
      vertebral bodies and intervertebral spaces between the conus medullaris and
      Tuffier's line, which is consistent regardless of sex or presence of transitional
      vertebra. However, because the conus medullaris and Tuffier's line become closer
      with age and the clinical use of Tuffier's line requires palpation through
      subcutaneous fat, caution must be exercised regarding selection of the
      intervertebral space, especially in the aged and obese population.

PMID- 14639150
TI  - Plastic change of N-type Ca channel expression after preconditioning is
      responsible for prostaglandin E2-induced long-lasting allodynia.
AB  - BACKGROUND: Although considerable evidence indicates neuronal Ca channels play
      significant roles in pain perception, their possible importance in
      hypersensitization after acute inflammation has not been investigated. METHODS:
      Using carrageenan for inducing hypersensitization, the authors investigated the
      analgesic effects of intrathecally administered N- and P/Q-type channel blockers,
      omega-conotoxin GVIA and omega-agatoxin IVA, respectively, and also examined the
      level of N-type channel expression. RESULTS: Acute inflammation, produced by
      carrageenan injection in a rat hind paw, caused mechanical hypersensitivity that
      resolved within several days. Injection of prostaglandin E2 into the same hind
      paw after resolution caused a markedly prolonged mechanical allodynia lasting
      more than 4 h. Similar but less potent prolonged allodynia was also induced in
      the contralateral hind paws. Intrathecal administration of omega-conotoxin GVIA
      (0.03-0.3 microg) produced dose-dependent inhibition of the allodynia in both
      control and carrageenan-preconditioned rats. However, the potency of omega
      conotoxin GVIA was significantly lower in carrageenan-preconditioned paws than in
      those in the contralateral and saline-preconditioned paws. In contrast, omega
      agatoxin IVA (0.01-0.1 microg) did not reduce the allodynia. Significant up
      regulation of N-type channel expression was observed in both dorsal root ganglia
      and the spinal cord ipsilateral to the carrageenan-preconditioned hind paw.
      CONCLUSIONS: The results suggest an aggravating role of the N-type channel in
      pain sensation and a selective plastic change of this channel expression that
      could underlie the mechanism of hypersensitization after acute inflammation.

PMID- 14639151
TI  - Tumescent local anesthesia for the surgical treatment of burns and postburn
      sequelae in pediatric patients.
AB  - BACKGROUND: Tumescent local anesthesia is a technique for regional anesthesia of
      the skin and the subcutaneous tissue, using infiltration of large volumes of
      local anesthetic. The advantages of this technique are (1) simplicity, (2)
      prolonged postoperative analgesia, (3) low incidence of bleeding, and (4)
      anesthetization of a large area of the body. There are no reports on the use of
      tumescent local anesthesia in pediatric patients. METHODS: In 30 consecutive
      pediatric burn patients with American Society of Anesthesiologists physical
      status class I or II who were 1-120 months old (34 +/- 31.6 months), after
      induction of anesthesia with nitrous oxide-oxygen-sevoflurane, infiltration with
      0.05% (14 ml/kg) or 0.1% (7 ml/kg) lidocaine solution was performed. Anesthesia
      was maintained with patients spontaneously breathing with 1.5% sevoflurane in
      nitrous oxide-oxygen (50%). The maximum dose of lidocaine used was 7 mg/kg.
      Postoperative pain was assessed by using the Children's Hospital of Eastern
      Ontario Pain Scale (for patients aged up to 5 yr) and by using a visual analog
      scale (for patients older than 5 yr). A comparison with a historic control group
      not treated with the tumescent local anesthesia technique was performed. RESULTS:
      No patients were excluded from the study, and no significant variations in the
      monitored intraoperative parameters were observed. Five patients had an increase
      in heart rate and respiratory rate at the beginning of surgery, and of these, two
      needed a temporary increase in sevoflurane concentration. After the initial
      incision, no response to painful stimulus was observed. No complications
      occurred. Six patients required postoperative acetaminophen administration, and
      24 patients did not require analgesic treatment. CONCLUSIONS: Tumescent local
      anesthesia with maximum dose of 7 mg/kg lidocaine seems to be safe and the sole
      possible effective locoregional anesthesia technique for the surgical treatment
      of noncontiguous pediatric burns.

PMID- 14639152
TI  - Dural tissue trauma and cerebrospinal fluid leak after epidural needle puncture:
      effect of needle design, angle, and bevel orientation.
AB  - BACKGROUND: The effects of epidural needle design, angle, and bevel orientation
      on cerebrospinal fluid leak after puncture have not been reported. The impact of
      these factors on leak rate was examined using a dural sac model. Dural trauma was
      examined using scanning electron microscopy. METHODS: Human cadaveric dura,
      mounted on a cylindrical model, was punctured with epidural needles using a
      micromanipulator. Tissue was punctured at 15 cm H2O (left lateral decubitus)
      system pressure, and leak was measured at 25 cm H2O (semisitting) pressure. Leak
      rates and trauma were compared for the following: (1) six different epidural
      needles at 90 degrees, bevel parallel to the dural long axis; (2) 18-gauge Tuohy
      and 18-gauge Special Sprotte epidural needles, 30 degrees versus 90 degrees; (3)
      18-gauge Tuohy, bevel perpendicular versus parallel to the dural long axis.
      RESULTS: With the 90 degrees puncture, bevel parallel, the greatest leak occurred
      with a 17-gauge Hustead (516 +/- 319 ml/15 min), and the smallest leak occurred
      with a 20-gauge Tuohy (100 +/- 112 ml/15 min; P = 0.0018). A 20-gauge Tuohy
      puncture led to statistically significant reductions in leak (P value range,
      0.0001-0.0024) compared with all needles except the Special Sprotte. With the 30
      degrees versus 90 degrees angle, 30 degrees punctures with an 18-gauge Tuohy
      produced nonstatistically significant leak reductions compared with the 18-gauge
      Tuohy at 90 degrees. The puncture angle made no difference for the Special
      Sprotte. Nonsignificant reductions were found for the Special Sprotte compared
      with the Tuohy. With the 18-gauge Tuohy bevel orientation, perpendicular
      orientation produced nonstatistically significant reductions in leak compared
      with parallel orientation. CONCLUSIONS: Cerebrospinal fluid leak after puncture
      was influenced most by epidural needle gauge. Leak rate was significantly less
      for the 20-gauge Tuohy needle.

PMID- 14639153
TI  - A randomized sequential allocation study to determine the minimum effective
      analgesic concentration of levobupivacaine and ropivacaine in patients receiving
      epidural analgesia for labor.
AB  - BACKGROUND: This study was designed to determine and compare the minimum local
      analgesic concentrations of levobupivacaine and ropivacaine when used in epidural
      obstetric analgesia. METHODS: In a double-blind study, healthy women requiring
      epidural analgesia for labor pain were randomized to receive either ropivacaine
      or levobupivacaine. Drugs were administered as a 20-ml epidural bolus. The
      concentration of each started at 0.11% and increased or decreased at intervals of
      0.01%, depending on the response of the previous patient, using the technique of
      up-down sequential allocation. Minimum local analgesic concentrations were
      calculated using the formula of Dixon and Massey. Efficacy was assessed using
      visual analog pain scores and motor and sensory block assessments, and safety was
      assessed by recording maternal and fetal/neonate vital signs and adverse events.
      RESULTS: Forty-seven patients received levobupivacaine, and 47 received
      ropivacaine. Minimum local analgesic concentrations for levobupivacaine (0.077%;
      95% CI, 0.058-0.096%) were lower than those for ropivacaine (0.092%; 95% CI,
      0.082-0.102%). The 0.015% difference was not statistically significant. There was
      no notable difference between treatment groups in the proportion of patients
      reporting drug-related adverse events. CONCLUSIONS: Levobupivacaine was 19% more
      potent than ropivacaine and provided similar safety results.

PMID- 14639154
TI  - Cervical and high thoracic ligamentum flavum frequently fails to fuse in the
      midline.
AB  - BACKGROUND: Cervical and high thoracic epidural anesthesia and analgesia have
      gained increasing importance in the treatment of painful conditions and as
      components of anesthetics for cardiac and breast surgery. In contrast to the
      hanging-drop technique, the loss-of-resistance technique is thought to rely on
      the penetration of the ligamentum flavum. However, the exact morphology of the
      ligamentum flavum at different vertebral levels remains controversial. Therefore,
      the aim of this study was to investigate the incidence and morphology of cervical
      and high thoracic ligamentum flavum mid-line gaps in embalmed cadavers. METHODS:
      Vertebral column specimens were obtained from 52 human cadavers. On each
      dissected level, ligamentum flavum mid-line gaps were recorded and evaluated with
      respect to shape and size. RESULTS: The following variations were encountered:
      complete fusion in the mid-line, mid-line fusion with a gap in the caudal part,
      mid-line gap, and mid-line gap with widened caudal end. The incidence of mid-line
      gaps at the following levels was: C3-C4: 66%, C4-C5: 58%, C5-C6: 74%, C6-C7: 64%,
      C7-T1: 51%, Th1-Th2: 21%, Th2-Th3: 11%, Th3-Th4: 4%, Th4-Th5: 2%, and Th5-Th6:
      2%. The mean width of mid-line gaps was 1.0 +/- 0.3 mm. CONCLUSIONS: In
      conclusion, the present study shows that gaps in the ligamenta flava are frequent
      at cervical and high thoracic levels but become rare at the T3/T4 level and
      below, such that one cannot always rely on the ligamentum flavum as a perceptible
      barrier to epidural needle placement at these levels.

PMID- 14639155
TI  - A novel neuroimmune mechanism in cannabinoid-mediated attenuation of nerve growth
      factor-induced hyperalgesia.
AB  - BACKGROUND: Nerve growth factor (NGF) is central to processes involved in an
      inflammatory hyperalgesia. Administration of exogenous NGF induces a hyperalgesia
      that is dependent on local neutrophil influx. The effects of administration of
      the cannabinoid anandamide and the cannabimimetic palmitoylethanolamide on an NGF
      induced hyperalgesia and neutrophil accumulation were examined in this study.
      METHODS: Baseline hind limb withdrawal latencies to a noxious heat stimulus were
      recorded before intraplantar administration of NGF (1 microg in 0.05 ml) to the
      hind paw of 75 male Wistar rats. Anandamide or palmitoylethanolamide (a substance
      that has cannabinoid-like actions but little affinity for cannabinoid receptors)
      at doses of 10 and 25 mg/kg were given (intraperitoneally) immediately after NGF.
      CB1 (SR141716A) and CB2 (SR144528) receptor antagonists were coadministered with
      the higher dose of cannabinoids. Withdrawal latencies were expressed as
      difference from baseline. Seventy rats received intraplantar NGF and
      intraperitoneal treatments. Neutrophil accumulation in the injected paw was
      assessed using a myeloperoxidase assay. RESULTS: Administration of NGF reduced
      latencies consistent with hyperalgesia. Anandamide and palmitoylethanolamide
      significantly reduced this hyperalgesia. The action of anandamide was CB1
      receptor-mediated. SR144528 abrogated the action of palmitoylethanolamide. NGF
      also provoked neutrophil accumulation in the injected paw, denoted by an increase
      in myeloperoxidase. Palmitoylethanolamide significantly reduced neutrophil
      accumulation by an SR144528-sensitive action, whereas anandamide was without
      effect. CONCLUSIONS: NGF induced a thermal hyperalgesia that was attenuated by
      anandamide and palmitoylethanolamide. Only palmitoylethanolamide reduced
      neutrophil influx. Thus, cannabinoids show a neuronal CB1 receptor-mediated
      antihyperalgesic action and a separate inhibition of a proinflammatory
      neuroimmune process. Such a mechanism suggests a therapeutic site of analgesic
      action separable from central side effects.

PMID- 14639156
TI  - Development of neuropathic pain in the rat spared nerve injury model is not
      prevented by a peripheral nerve block.
AB  - BACKGROUND: The mechanisms responsible for initiation of persistent neuropathic
      pain after peripheral nerve injury are unclear. One hypothesis is that injury
      discharge and early ectopic discharges in injured nerves produce activity
      dependent irreversible changes in the central nervous system. The aim of this
      study was to determine whether blockade of peripheral discharge by blocking nerve
      conduction before and 1 week after nerve injury could prevent the development and
      persistence of neuropathic pain-like behavior in the spared nerve injury model.
      METHODS: Bupivacaine-loaded biodegradable microspheres embedded in fibrin glue
      were placed in a silicone tube around the sciatic nerve to produce a conduction
      block. After sensory-motor testing of block efficacy, a spared nerve injury
      procedure was performed. Development of neuropathic pain behavior was assessed
      for 4 weeks by withdrawal responses to stimulation (i.e., von Frey filaments,
      acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n =
      12) and in controls (n = 11). RESULTS: Bupivacaine microspheres treatment
      produced conduction blockade with a complete lack of sensory responsiveness in
      the sural territory for 6 to 10 days. Once the block wore off, the degree of
      hypersensitivity to stimuli was similar in both groups. CONCLUSIONS: Peripheral
      long-term nerve blockade has no detectable effect on the development of allodynia
      or hyperalgesia in the spared nerve injury model. It is unlikely that injury
      discharge at the time of nerve damage or the early onset of ectopic discharges
      arising from the injury site contributes significantly to the persistence of
      stimulus-evoked neuropathic pain in this model.

PMID- 14639157
TI  - Antinociceptive effect of morphine, but not mu opioid receptor number, is
      attenuated in the spinal cord of diabetic rats.
AB  - BACKGROUND: The mechanisms of decreased analgesic potency of mu opioids in
      diabetic neuropathic pain are not fully known. The authors recently found that G
      protein activation stimulated by the mu opioid agonist is significantly reduced
      in the spinal cord dorsal horn in diabetes. In the current study, they determined
      potential changes in the number and binding affinity of mu opioid receptors in
      the spinal cord in diabetic rats. METHODS: Rats were rendered diabetic with an
      intraperitoneal injection of streptozotocin. The nociceptive withdrawal threshold
      was measured before and after intrathecal injection of morphine by applying a
      noxious pressure stimulus to the hind paw. The mu opioid receptor was determined
      with immunocytochemistry labeling and a specific mu opioid receptor radioligand,
      [3H]-(D-Ala2,N-Me-Phe4,Gly-ol5)-enkephalin ([3H]-DAMGO), in the dorsal spinal
      cord obtained from age-matched normal and diabetic rats 4 weeks after
      streptozotocin treatment. RESULTS: The antinociceptive effect of intrathecal
      morphine (2-10 microg) was significantly reduced in diabetic rats, with an ED50
      about twofold higher than that in normal rats. However, both the dissociation
      constant (3.99 +/- 0.22 vs. 4.01 +/- 0.23 nm) and the maximal specific binding
      (352.78 +/- 37.26 vs. 346.88 +/- 35.23 fmol/mg protein) of [3H]-DAMGO spinal
      membrane bindings were not significantly different between normal and diabetic
      rats. The mu opioid receptor immunoreactivity in the spinal cord dorsal horn also
      was similar in normal and diabetic rats. CONCLUSIONS: The reduced analgesic
      effect of intrathecal morphine in diabetes is probably due to impairment of mu
      opioid receptor-G protein coupling rather than reduction in mu opioid receptor
      number in the spinal cord dorsal horn.

PMID- 14639158
TI  - Pulmonary arterial hypertension: pathophysiology and anesthetic approach.

PMID- 14639159
TI  - Current transfusion practices of members of the american society of
      anesthesiologists: a survey.
AB  - BACKGROUND: The last published survey of transfusion practices among members of
      the American Society of Anesthesiologists (ASA) was conducted in 1981. The ASA
      Committee on Transfusion Medicine conducted a new transfusion survey in 2002.
      METHODS: The survey was mailed to 2,500 randomly selected active ASA members. The
      previous survey was modified to incorporate questions based on the ASA Practice
      Guidelines for Blood Component Therapy. The chi-square test was used for
      comparisons. Two-tailed P values of 0.05 or less were considered as nonchance
      differences. RESULTS: A total of 862 survey responses were completed by
      anesthesiologists who provided or directly supervised anesthesia for patients who
      may have required transfusion. In a given week, 62% rarely or never transfused 3
      or more units of blood to the same patient. The percentage of anesthesiologists
      who responded that it is never or rarely (1% or less of the time) necessary to
      cancel elective surgery because of unavailability of blood products was 96% in
      2002. In 1981, 92% responded that it was rarely necessary, and 8% said that it
      was occasionally necessary. The percentage of anesthesiologists who required
      patients undergoing elective surgery to have a hemoglobin concentration of at
      least 10 g/dl decreased from 65% to 9% (P < 0.001). Before intraoperative
      erythrocyte transfusion, 89% of respondents performed hemoglobin or hematocrit
      determinations routinely or sometimes. Intraoperative autologous transfusion
      equipment availability increased from 39% to 95% (P < 0.001). Awareness of the
      ASA Guidelines was 72%. CONCLUSIONS: Transfusion practices have changed
      considerably since 1981. Current transfusion practices are, in general,
      consistent with the ASA Guidelines.

PMID- 14639160
TI  - Vaginal birth after cesarean delivery.

PMID- 14639161
TI  - Ropivacaine-induced cardiac arrest after peripheral nerve block: successful
      resuscitation.

PMID- 14639162
TI  - Cardiac arrest after injection of ropivacaine for posterior lumbar plexus
      blockade.

PMID- 14639163
TI  - Bispectral index scale is higher for halothane than sevoflurane during
      intraoperative anesthesia.

PMID- 14639164
TI  - Severe airway obstruction during arthroscopic shoulder surgery.

PMID- 14639165
TI  - Life-threatening airway edema resulting from prolonged shoulder arthroscopy.

PMID- 14639166
TI  - Severe ADU desflurane vaporizing unit malfunction.

PMID- 14639167
TI  - Noninvasive cardiac output performance improved after sufficient stabilization
      time following decrease of ventilation.

PMID- 14639168
TI  - Noninvasive cardiac output monitor algorithms are more sophisticated and perform
      better than indicated in modeling paper.

PMID- 14639169
TI  - Ralph Milton Waters, M.D.

PMID- 14639170
TI  - Who invented the "jaw thrust"?

PMID- 14639171
TI  - [Three challenges for the journal].

PMID- 14639172
TI  - [Requirement for multiple-facility hospital structures to meet the needs of lung
      cancer patients].

PMID- 14639173
TI  - [Non-invasive ventilation at home: preset volume or pressure?].

PMID- 14639174
TI  - [Nonspecific interstitial pneumonitis: a new anatomoclinical entity among
      idiopathic diffuse interstitial pneumonias].
AB  - Nonspecific interstitial pneumonitis with fibrosis has been individualized within
      the group of idiopathic diffuse interstitial pneumonias by pathological criteria.
      It is differentiated from usual interstitial pneumonitis by the temporal
      uniformity of the lesions, a prominent inflammatory interstitial infiltration,
      and the absence of honeycombing. Clinical and functional symptoms are those of
      diffuse interstitial pneumonitis. An etiology may be found in about half the
      cases, including connective tissue disease, exposure to organic antigens, or
      recent acute lung injury. Computed tomography of the chest shows bilateral ground
      glass opacities, and alveolar opacities with a peribronchiolar or patchy
      distribution. Prognosis is rather good, since a majority of patients improve when
      treated with corticosteroids or with an association of corticosteroids and
      immunosuppressive drugs. These etiologic and prognostic features justify the
      individualization of nonspecific interstitial pneumonitis with fibrosis as a
      distinct clinicopathological entity.

PMID- 14639175
TI  - [Hospitalization facilities required for quality care of lung cancer patients].
AB  - The purpose of this study was to determine whether good-quality care for patients
      with lung cancer can be delivered without a full hospitalization unit. Our study
      included all consecutive untreated lung cancer patients admitted over a two-year
      period. The following criteria were analyzed retrospectively: residence, age,
      sex, histology, staging, treatments, administrative data during the first 6
      months of treatment, place of death, and duration of last stay before death in
      the unit. Two hundred six patients were recorded. Twenty-eight percent of the
      patients had stage IIIB disease and 61% stage IV disease. The first treatment
      included: surgery (12%), chemotherapy (80%). During the first six months, the
      median number of hospitalizations was 8 and the median number of full
      hospitalization days was 17 compared with 6 days for one-day stays. The median
      duration of the first stay was 5 days whereas the duration of the last one was 3
      days. During the first year, 71% of the patients dies: 36% in our unit (47% of
      them were inpatients for more than 6 days during their last stay). Diagnosis,
      initial treatment, management of treatment complications and supportive care are
      not compatible with weekly hospitalization. Full hospitalization is mandatory for
      good-quality care in a referral cancer unit.

PMID- 14639176
TI  - [Comparison of volume preset and pressure preset ventilators during daytime nasal
      ventilation in chronic respiratory failure].
AB  - Both volume preset and pressure preset ventilators are available for domiciliary
      nasal ventilation. Owing to their technical characteristics, it has been
      suggested that impaired ventilatory mechanics might cause a drop in the tidal
      volume (Vt) delivered by pressure preset devices, thereby placing mechanical
      ventilation at risk of inefficacy. We have assessed two ventilator systems (one
      pressure preset and one volume preset) with regard to the tidal volume and end
      tidal carbon dioxide tension (PetCO(2)) changes that may be achieved in a group
      of awake patients with stable chronic respiratory failure (CRF). Eleven patients
      with stable CRF were ventilated in the assist/control mode for two consecutive
      one-hour periods. One ventilator was tested each hour, in random order. The
      VIGIL'AIR(R) system was used to record Vt, Respiratory Rate (RR), and
      Inspiratory/Expiratory ratio (I/E). The deviation E (E=preset value - measured
      value) was calculated for each measurement. Changes in PetCO(2) and arterial
      oxygen saturation were determined respectively by a capnometer and a pulse
      oximeter. Comparison of the mean deviation of Vt calculated for the two
      ventilators revealed a difference in patients with chronic obstructive pulmonary
      disease (COPD). The deviation was greatest with the pressure preset ventilator
      (PPV), which gave mean measured values higher than the mean preset values. The
      same comparison failed to reveal any difference in restrictive CRF. Comparison of
      the volume preset and pressure preset ventilators for RR, I/E and PetCO(2) did
      not reveal any difference. Compared to the volume preset ventilator, the efficacy
      of PPV to ventilate is not affected by the restrictive or obstructive nature of
      CRF. Our results show that pressure-preset ventilator is an adequate alternative
      to the volume-preset device for daytime non invasive ventilation in chronic
      respiratory insufficiency.

PMID- 14639177
TI  - [Obstructive sleep syndrome, a prospective multicentric study (SASOM)].
AB  - A prospective multicentric study ("SASOM" for "Syndrome d'Apnees du Sommeil") was
      carried out from 1996 to 1998 among pulmonary departments of 57 French general
      Hospitals, about diagnostic, treatment and outcome of Obstructive Sleep Apnea
      Syndrome (OSAS). All successive adult patients diagnosed by polygraphic recording
      as having OSAS were included. Mean characteristics of the 1720 patients (1455 M,
      245 W) were as follows: age 58 years, BMI 34, FEVI 86%, VC 88%, PO2 77 mmHg,
      PCO(2) 42 mmHg, AHI 46. Other determined values were: clinical signs, systemic
      hypertension, treatment, follow-up during 18 months. Main results were: - there
      was a strong correlation between clinical signs and AHI, - 70% of the patients
      (n=1227) were treated with CPAP; among them, withdrawals were 7% at 6 months, 15%
      at 1 year, 20% at 18 months, 24% at 2 years, - among patients whose AHI was<30,
      and who were treated, withdrawals were 33% at 18 months, - there was non
      difference of diagnostic, treatment and follow-up according to the modalities of
      the diagnostic (ventilation polygraphy of full polysomnography). CONCLUSION:
      Among a large population of 1720 OSAS without any selection in this multicentric
      study: - clinical signs are correlated with AHI, - a full polysomnography is not
      required of the initial diagnosis, - among the less severe patients who are
      treated by CPAP, the compliance is quite good at 18 months.

PMID- 14639178
TI  - [Thoracic nocardiasis associated with macrophage activation syndrome].
AB  - Nocardiasis is an uncommon bacterial disease often observed in immunodepressed
      patients. Its interactions with the immune system remain poorly known. We report
      a case of Nocardia asteroides thoracic nocaridiasis in an African subject who
      also had macrophage activation syndrome. We recall the classic data on
      nocardiasis in Africa and emphasize the importance of emergence in HIV-infected
      subjects. The association between nocardiasis and macrophage activation syndrome
      suggest a possible pathogenic mechanism involving the immune system (lymphocytes
      and macrophages) and Nocardia asteroides.

PMID- 14639179
TI  - [Mediastinal sarcoidosis and vascular thrombosis: a fortuitous association?].
AB  - A 43-year-old woman presented with a recent history of intermittent dyspnea with
      wheezing. The chest x-ray evidenced mediastinal nodes. A CT scan showed vascular
      embolism. Mediastinoscopy was performed and pathology examination of the node
      confirmed the diagnosis of sarcoidosis. The patient responded to corticosteroid
      and anticoagulation therapy. Is this a fortuitous association? A vascular
      localization of sarcoidosis? Thrombosis by compression?

PMID- 14639180
TI  - [Mediastioscopic management of pleuropericardial cysts].
AB  - We report two cases of paratracheal cystic tumors where no preoperative diagnosis
      could be established. Mediastinoscopy provided the diagnosis of pleuropericardial
      cyst. The mediastinoscopic approach allowed partial removal in one case and
      complete removal in the other.

PMID- 14639181
TI  - [Spontaneous resolution of a giant pulmonary bulla].
AB  - There are different causes leading to formation of pulmonary bullae, in
      particular tuberculosis. There is some debate concerning the pathophysiology of
      bullae extension although two mechanisms are put forward: partial obstruction of
      the airways and elastic recoil of adjacent lung parenchyma with a negative
      pressure in the bullae. Pulmonary function tests are highly perturbed in patients
      with giant bullae. The natural history of bullae is enlargement although
      spontaneous regression is rarely described. Bullae should be resected in selected
      patients, others require careful follow-up. We present the case of a man with
      tuberculosis who developed a giant pulmonary bulla that regressed spontaneously
      in a few years.

PMID- 14639182
TI  - [Primary pleural lymphoma: a rare complication of tuberculosis pleural sequelae].
AB  - We report two cases of malignant lymphoma of B phenotype occurring after
      therapeutic pneumothorax for tuberculosis. In both cases, outcome was fatal
      without time for specific treatment. Mainly reported in Japan, this pathology
      seems to be less frequent in western countries. As for B phenotype lymphoma
      associated with immunodeficiency, association with Epstein Barr virus is
      reported. Definite diagnosis is difficult and requires surgical biopsy. Prognosis
      remains poor with a survival ranging from 3 to 6 month.

PMID- 14639183
TI  - [An unusual opacity of the right base].
AB  - The scimitar syndrome or pulmonary venolobar syndrome is a rare, complex and
      variable malformation of the right lung characterized by an abnormal right sided
      pulmonary venous drainage in the inferior vena cava, malformation of the right
      lung, abnormal arterial supply and sometimes cardiac malformations. We present a
      case in which this diagnosis was suspected on an abnormal routine chest
      radiograph in a 38-year-old asymptomatic woman. Most patients are asymptomatic;
      symptomatic patients have a marked left-to-right shunt or a severe congenital
      heart disease. They usually suffer from shortness of breath, asthenia or repeated
      chest infections. Usually, the posteroanterior chest radiograph can confirm the
      diagnostic. It shows the abnormal vein draining into the inferior vena cava as a
      curved vascular shadow with a scimitar like appearance. However, in some cases,
      when the scimitar vein is masked by the overlying cardiac shadow, computed
      tomography, angiography and magnetic resonance imaging can be helpful by showing
      the abnormal vein and its insertion into the inferior vena cava. Scimitar
      syndrome seldom necessitates surgical intervention. However, repeated lung
      infections can sometimes require lobectomy or pneumonectomy, left-to-right shunt
      vascular surgery to redirect the scimitar vein into the left atrium.

PMID- 14639184
TI  - [Management of chronic pain in cancer patients: practical applications].

PMID- 14639185
TI  - [Environment and drugs. Introduction].

PMID- 14639186
TI  - [Molecules used for therapeutic or diagnostic purposes are micro water
      polluants].
AB  - Molecules used for therapeutic or diagnostic purposes have been identified and
      quantified in Europe and North America in surface and ground waters used for
      production of drinking water. When mixed with other organic compounds such as
      pesticides, hydrocarbons, or plasticizers which may present endocrine-disturbing
      or genotoxic effects, such molecules may, even in low concentrations, present an
      ecotoxicological or public health hazard. For this reason, healthcare
      professionals involved in drug production as well as drug users must take care to
      limit release of such molecules into the environment. Work on environmental
      behavior of marketed products and on health hazard assessment must be favored in
      order to acquire appropriate knowledge of the environmental and health risks.

PMID- 14639187
TI  - [Hospital and environment: waste disposal].
AB  - Like all production units, hospitals produce waste and are responsible for waste
      disposal. Hospital waste is particular due to the environmental risks involved,
      particularly concerning infection, effluents, and radionucleide contamination.
      Management plans are required to meet environmental, hygiene and regulatory
      obligations and to define reference waste products. The first step is to optimize
      waste sorting, with proper definition of the different categories, adequate
      containers (collection stations, color-coded sacks), waste circuits, intermediate
      then central storage areas, and finally transfer to an incineration unit. Volume
      and delay to elimination must be carefully controlled. Elimination of drugs and
      related products is a second aspect: packaging, perfusion pouches, tubing,
      radiopharmaceutic agents. These later products are managed with non-sealed
      sources whose elimination depends on the radioactive period, requiring selective
      sorting and specific holding areas while radioactivity declines. Elimination of
      urine and excreta containing anti-cancer drugs or intravesical drugs,
      particularly coming from protected rooms using radioactive iodine is another
      aspect. There is also a marginal flow of unused or expired drugs. For a health
      establishment, elimination of drugs is not included as part of waste disposal.
      This requires establishing a specific circuit with selective sorting and
      carefully applied safety regulations. Market orders for collecting and handling
      hospital wastes must be implemented in compliance with the rules of Public Health
      Tenders.

PMID- 14639188
TI  - [Action of the pharmaceutical industry].
AB  - The presence of drugs in the environment, principally in water, can be detected
      analytically. Although concentrations detected are very low, their presence
      raises the issue of the impact on the natural medium and human health. In the
      first part of this review, we attempt to answer some of the most frequently asked
      questions: why are drugs found in the environment? where do they come from? is
      there a health hazard? In the second part, we describe measures taken by the
      pharmaceutical industry to protect the environment. Action is taken to control
      waste from production sites but also to coordinate the efforts of the
      pharmaceutical profession via CYCLAMED. Collection and reuse of unused drugs is
      also discussed.

PMID- 14639189
TI  - [Environment and drugs. Conclusion].

PMID- 14639190
TI  - [Taurine: a particular aminoacid with multiple functions].
AB  - Taurine has multiple biological and metabolic functions: this particular B-amino
      acid is an antioxidant, it conjugates biliary acids, detoxifies some xenobiotics
      and modulates intracellular calcium levels. Moreover, taurine plays an important
      part in osmoregulation, neuromodulation and stabilization of the membranes.
      Taurine is looked upon as an "essential amino acid" in some particular situations
      associating inadequate intake or synthesis and major loss of biliary salts.
      Clinically, taurine has been used with varying degrees of success in the
      treatment of several pathologies (cardiovascular diseases, cystic fibrosis,
      alcoholism, retinal degeneration, hepatic disorders). Being found in the
      secretions of the mammalian reproductive tract, it preserves the motility of the
      spermatozoa, supports their capacitation, improves the chances of success of
      fertilization and the early embryonic development. This is why it can be found in
      some culture media for in vitro fertilization.

PMID- 14639191
TI  - [Modeling the kinetics of theophylline release from a semi-solid matrix:
      Gelucire].
AB  - Controlling release of a trace is an indispensable pharmacological technique.
      Release of the active substance can be modulated to meet the desired kinetic
      requirements of the formulation by carefully choosing the excipient and
      controlling the solubility of the tracer. We studied the preformulation of a semi
      solid matrix, Gelucire, to examine the kinetic properties of theophylline
      release. Several models were analyzed. The results show that the formulation must
      be specific for the semi-solid matrix used.

PMID- 14639192
TI  - [Are acute toxicity testing and the three Rs rule reconcilable? Example of the
      lethal dose 50 determination].
AB  - Toxicity assessment and demonstration of innocuousness of chemical compounds have
      been part of the research studies conducted in the fields of pharmacy,
      agriculture and chemical industry for years. Acute systemic toxicity studies are
      an important element of the safety evaluation. They remain compulsory for
      regulatory purposes and important for the public opinion that does not accept the
      risk anymore. Evolutions of the ethics in animal experiments foster a necessary
      reduction of the number of animals involved in this type of experiments,
      following the well-known principle of the three Rs rule of Russell and Burch
      (1959) (Reduction, refinement and replacement). These two views seem in
      contradiction. Using the example of acute toxicity testing and focusing on the
      now very criticized parameter lethal dose 50, we will present approaches,
      including statistical ones, that a toxicologist can use, when free to choose, to
      keep on conducting the indispensable in vivo studies while abiding by ethical
      recommendations.

PMID- 14639193
TI  - [Infrared spectrophotometry: a versatile analytical tool in hospital pharmacy].
AB  - Pharmacy services in healthcare facilities have increasing analytical needs, as
      frequently recalled by good practices guidelines (hospital pharmacy good
      practices, hospital pharmaceutical preparations good practices). Various
      analytical methods can be employed, from spot tests to the most recent
      chromatographic methods. The purpose of this paper is to demonstrate, with two
      concrete examples, the versatility and pertinence of one of these analytical
      methods: infrared spectrophotometry. We describe two current applications, used
      in a hospital pharmacy service: identification of pharmaceutical raw material and
      dose control of cytotoxic injectable preparations.

PMID- 14639194
TI  - [Formulation and stability of hospital preparation of 3,4-diaminopyridine
      capsules].
AB  - Administration of 3,4-diamynopyridine (3,4-DAP) has been found to be effective in
      the symptomatic treatment of patients with Eaton-Lambert Myasthenic syndrome. A
      recent case of this syndrome in Val de Grace Military hospital led us to
      manufacture 3,4-DAP capsules. In agreement with good manufactoring processes, we
      have performed mass uniformity and content tests. Six different formulations were
      tested, starch maize and magnesium stearate have been validated as excipients.
      The stability study showed that the conservation was good even under extreme
      conditions. Clinical and electromyographic improvement seen in this patient
      suggests this preparation may be of benefit.

PMID- 14639196
TI  - Smoking and women. How to overcome barriers and quit.

PMID- 14639197
TI  - Experts reassuring about cholesterol drugs.

PMID- 14639198
TI  - New pain relief drugs and heart attacks.

PMID- 14639195
TI  - [Formulation and stability study of sucred solutions for a clinical trial in
      neonates].
AB  - A randomized, double blind clinical trial have been initiated in the neonatology
      unit of CHRU in Lille to compare the analgesic effect of two oral solutions (25%
      dextrose and 30% glucose) after heel prick sampling. As part of this trial, the
      pharmacy was asked to perform the preparation and the randomization. In agreement
      with good clinical practices and good manufacturing practices, we have valided
      manufacturing processes, and performed microbiological tests, chromatography
      control and polarimetric dosage. The stability study of solutions (six months),
      allows preparation of only one batch in accordance with good manufacturing
      practice for 25% sucrose and 30% glucose. The participation of hospital
      pharmacist in the preparation of investigational products is becoming more and
      more frequent. This enhances his involvement in the quality control of clinical
      trials.

PMID- 14639199
TI  - Heart tests for women.

PMID- 14639200
TI  - Spinal stenosis. Low back pain may be degenerative disease.

PMID- 14639202
TI  - Personal trainers. Can they help you get in shape?

PMID- 14639201
TI  - Hashimoto's disease.

PMID- 14639203
TI  - One on one. Can I take hormone therapy for menopause if I have endometriosis?

PMID- 14639204
TI  - One on one. What is flaxseed and what does it do?

PMID- 14639206
TI  - Mayo Clinic office visit. Female sexual dysfunction.

PMID- 14639205
TI  - One on one. Can resistance exercise burn calories as well as aerobic exercise
      can?

PMID- 14639207
TI  - The skinny on skin. Caring for your skin as you age.

PMID- 14639208
TI  - Overactive bladder. How to keep it from controlling your life.

PMID- 14639209
TI  - High bone density and breast cancer risk.

PMID- 14639210
TI  - Excess weight linked to early heart attacks.

PMID- 14639212
TI  - Multiple sclerosis. Hope and help for this mysterious illness.

PMID- 14639211
TI  - Physical activity helps keep aging minds sharp.

PMID- 14639214
TI  - Scleroderma.

PMID- 14639213
TI  - Blepharoplasty. Giving droopy eyelids a lift.

PMID- 14639216
TI  - One on one. How much soy do I need to eat each day to help lower my cholesterol?

PMID- 14639215
TI  - Food additives. Are they safe?

PMID- 14639217
TI  - One on one. I've taken the thyroid medication Synthroid for years. Now I hear the
      Food and Drug Administration is raising concerns about the drug and may take it
      off the market. What's the story?

PMID- 14639218
TI  - Mayo Clinic office visit. Taking care of your back.

PMID- 14639220
TI  - Weekly birth control patch offers alternatives.

PMID- 14639219
TI  - New cholesterol guidelines. Panel pushes preventative measures.

PMID- 14639221
TI  - Diet and exercise may prevent diabetes.

PMID- 14639222
TI  - Usefulness of breast self-exams is questioned.

PMID- 14639223
TI  - Anxiety disorders. Calming fears, phobias and worries.

PMID- 14639224
TI  - Hearing loss. What to do when sound fades.

PMID- 14639225
TI  - Tinnitus.

PMID- 14639226
TI  - Aromatherapy. Can scents heal?

PMID- 14639227
TI  - One on one. What does it mean if my blood pressure is different in each arm?

PMID- 14639228
TI  - One on one. What causes "cottage cheese" thighs?

PMID- 14639229
TI  - One on one. Which is better for persistent heartburn, surgery or antacid
      medications?

PMID- 14639230
TI  - Mayo Clinic office visit. Palliative care.

PMID- 14639232
TI  - People with diabetes urged to get their blood pressure down.

PMID- 14639231
TI  - Energy density. How to eat more and achieve a healthy weight.

PMID- 14639234
TI  - Calcium's brush with lead.

PMID- 14639233
TI  - Could a patch help female sexual dysfunction?

PMID- 14639235
TI  - Medical marvels. 'Gee whiz' technology in the making.

PMID- 14639236
TI  - Pneumonia. Lung infection is both common and serious.

PMID- 14639237
TI  - Cystic fibrosis.

PMID- 14639239
TI  - One on one. Is aspartame safe to use?

PMID- 14639238
TI  - Women at work. Learning to get along with co-workers.

PMID- 14639240
TI  - One on one. Do HEPA filters relieve asthma symptoms?

PMID- 14639241
TI  - One on one. Could my artificial nails be harboring germs?

PMID- 14639242
TI  - Mayo Clinic office visit. HIV in women.

PMID- 14639243
TI  - Programmed to age. How your genes affect longevity.

PMID- 14639245
TI  - No link found between power lines and breast cancer.

PMID- 14639244
TI  - Quick defibrillation is important.

PMID- 14639246
TI  - Protective gene mutation may help people with HIV.

PMID- 14639247
TI  - Changes with age.
AB  - Aging is a complex combination of nature and nurture, with not more than one
      third being genetically determined. Your lifestyle choices and environment
      determine much of how long and how well you live.

PMID- 14639248
TI  - Women and HIV/AIDS.

PMID- 14639249
TI  - Disease dictionary. Pseudogout.

PMID- 14639250
TI  - Hard-to-resist exercises.

PMID- 14639251
TI  - Is it safe to eat discolored potatoes?

PMID- 14639252
TI  - Does having a dry mouth increase my risk of cavities?

PMID- 14639253
TI  - Does having your fallopian tubes tied affect when menopause occurs?

PMID- 14639254
TI  - Mayo Clinic office visit. Menstrual manipulation.

PMID- 14639255
TI  - Bone density testing. Who needs it and when?

PMID- 14639256
TI  - New medication promising for osteoporosis.

PMID- 14639257
TI  - Sleep position may affect kidney stone recurrence.

PMID- 14639258
TI  - Folic acid intake may reduce breast cancer risk associated with alcohol.

PMID- 14639259
TI  - Herpes. Taming a sneaky virus.

PMID- 14639260
TI  - Breast reduction. Breast surgery that can improve your health.

PMID- 14639262
TI  - Weightlifting alternatives. Gentle ways to build strength.

PMID- 14639261
TI  - Primary biliary cirrhosis.

PMID- 14639263
TI  - One on one. Why do people who smoke seem to have more wrinkled faces than people
      who don't smoke?

PMID- 14639264
TI  - One on one. Do thin people still need to exercise?

PMID- 14639266
TI  - Mayo Clinic office visit. Alternative treatments for hot flashes.

PMID- 14639265
TI  - One on one. Why won't my doctor give me an antibiotic when I have a really bad
      cold?

PMID- 14639268
TI  - Low bone density may predict risk of stroke in women.

PMID- 14639267
TI  - Old wives' tales. Oral tradition meets medical fact.

PMID- 14639269
TI  - Older people can benefit from joint replacement surgery.

PMID- 14639270
TI  - Risk of breast cancer may not be what you think.

PMID- 14639271
TI  - Anemia. Help for wimpy red blood cells.

PMID- 14639272
TI  - Hives. Skin eruptions usually more irritating than serious.

PMID- 14639273
TI  - Legionnaires' disease.

PMID- 14639274
TI  - Cooking oils. Variety contributes to good taste and good health.

PMID- 14639275
TI  - One on one. What foods can I eat and which ones should I avoid if I have
      diverticulosis?

PMID- 14639276
TI  - One on one. Once I start taking blood pressure medication, do I need to stay on
      it forever?

PMID- 14639277
TI  - One on one. I'm an alcoholic but haven't had a drink in several years. Can I ever
      go back to drinking occasionally?

PMID- 14639278
TI  - Mayo Clinic office visit. Breast imaging.

PMID- 14639279
TI  - Osteoporosis. Helping your bones last a lifetime.

PMID- 14639280
TI  - Hormone replacement therapy revisited.

PMID- 14639281
TI  - Once-a-week alendronate easier on stomach.

PMID- 14639282
TI  - Women and smoking. The U.S. Surgeon General's report.

PMID- 14639284
TI  - Melanoma. Getting a grip on a deadly skin cancer.

PMID- 14639283
TI  - Mothers influence the milk-drinking habits of their daughters.

PMID- 14639285
TI  - Smell and taste disorders. What to do when food loses its appeal.

PMID- 14639286
TI  - Sarcoidosis.

PMID- 14639288
TI  - One on one. I heard you can have a full-body CT scan that can tell you about your
      health. Is it worth getting?

PMID- 14639287
TI  - Optimism. Positive thinking may improve your health.

PMID- 14639290
TI  - Mayo Clinic office visit. Hormone replacement therapy and your heart - changing
      research.

PMID- 14639289
TI  - One on one. Is there any help for the lack of interest in sex I've experienced
      since undergoing chemotherapy?

PMID- 14639291
TI  - Fat facts. Answering your questions about dietary fats.

PMID- 14639292
TI  - Livestock diseases confusing to Americans.

PMID- 14639293
TI  - New kidney transplant procedure reduces organ rejection.

PMID- 14639294
TI  - Everyday injuries. Handling life's little emergencies.

PMID- 14639295
TI  - Food allergies. Uncommon but potentially dangerous.

PMID- 14639296
TI  - Cushing's disease.

PMID- 14639297
TI  - Straighten up. How to improve your posture.

PMID- 14639298
TI  - One on one. What makes my eyelashes grow inward and scratch my eyes?

PMID- 14639299
TI  - One on one. Can a supplement of 5-HTP help relieve my depression?

PMID- 14639300
TI  - One on one. Will taking calcium supplements make my nails stronger?

PMID- 14639302
TI  - Metabolism. How your body uses energy.

PMID- 14639301
TI  - Mayo Clinic office visit. Blood pressure basics.

PMID- 14639303
TI  - Conflicting diet advice leads to nutrition backlash.

PMID- 14639304
TI  - Marital stress may be hard on the heart.

PMID- 14639305
TI  - Mammograms are worth the anxiety.

PMID- 14639306
TI  - Congestive heart failure. Living with a weakened pump.

PMID- 14639307
TI  - Visual disturbances. What causes them; What to do about them.

PMID- 14639308
TI  - Shingles.

PMID- 14639309
TI  - Grain guide. Moving beyond white bread and rice.

PMID- 14639310
TI  - One on one. Are there ways to clean out your colon before a colonoscopy that
      aren't so yucky?

PMID- 14639311
TI  - One on one. What is chelation therapy used for?

PMID- 14639312
TI  - Mayo Clinic office visit. Advances in preventing colorectal cancer.

PMID- 14639314
TI  - Mayo Clinic builds a new pyramid.

PMID- 14639313
TI  - Cardiac rehabilitation. How to live better with heart disease.

PMID- 14639315
TI  - Non-Hodgkin's lymphoma. When your lymphatic system gets cancer.

PMID- 14639316
TI  - Fingernails. Keeping them healthy and strong.

PMID- 14639317
TI  - Osteomalacia.

PMID- 14639318
TI  - Pet power. Animals can boost your health and emotional well-being.

PMID- 14639320
TI  - One on one. Do electric toothbrushes clean your teeth better than standard
      toothbrushes?

PMID- 14639319
TI  - One on one. Do I need to take antibiotics after I have hip replacement surgery?

PMID- 14639321
TI  - One on one. Does natural progesterone cream work for menopausal symptoms?

PMID- 14639322
TI  - Mayo Clinic office visit. Cutting edge research on women's health.

PMID- 14639323
TI  - Intimacy as you age.

PMID- 14639324
TI  - In-flight medicine. Handling illness at 30,000 feet.

PMID- 14639325
TI  - Over-the-counter cold ingredient gets the ax.

PMID- 14639326
TI  - High systolic blood pressure linked to stroke risk, too.

PMID- 14639328
TI  - Building support for your pelvic floor.

PMID- 14639327
TI  - Grumpiness may fade with exercise.

PMID- 14639329
TI  - Cough. The good, the bad, the chronic.

PMID- 14639330
TI  - Atrial septal defect.

PMID- 14639331
TI  - Fitness fact or fiction? Trusting the wrong advice can hamper your fitness
      efforts.

PMID- 14639332
TI  - One on one. I've seen those new fruit and vegetable washes and wonder if I need
      to use them?

PMID- 14639334
TI  - One on one. I recently saw a new sugar substitute at the market called Splenda.
      What is it, and is it safe?

PMID- 14639333
TI  - One on one. Does an allergy to penicillin last forever?

PMID- 14639335
TI  - Mayo Clinic office visit. Caring for your skin.

PMID- 14639336
TI  - Alzheimer's disease. Advances in treatment offer hope.

PMID- 14639338
TI  - Tripped up by a meal.

PMID- 14639337
TI  - Oral contraceptives linked to breast cancer?

PMID- 14639339
TI  - When kidneys fail. Recognizing and treating renal disease.

PMID- 14639340
TI  - Dental implants. An alternative to your own teeth.

PMID- 14639341
TI  - Bronchiectasis.

PMID- 14639342
TI  - What's for breakfast? Healthy choices can give your day a boost.

PMID- 14639343
TI  - One on one. Since calcium is now added to so many foods,can I wind up getting too
      much?

PMID- 14639344
TI  - One on one. I heard that cooked vegetables have more antioxidants than raw ones.
      Is this true?

PMID- 14639345
TI  - One on one. Why does my eyelid twitch, and what can be done about it?

PMID- 14639346
TI  - Mayo Clinic office visit. Testosterone and women.

PMID- 14639347
TI  - The role of poxviruses in tumor immunotherapy.

PMID- 14639348
TI  - Recruiting faculty: a science and an art.

PMID- 14639349
TI  - Mentoring faculty members.

PMID- 14639350
TI  - The challenge of faculty retention: a personal reflection.

PMID- 14639351
TI  - Surgical treatment of sacrococcygeal pilonidal sinus with the Limberg
      transposition flap.
AB  - BACKGROUND: Pilonidal sinus is a common chronic disease of the sacrococcygeal
      region. Although many surgical methods have been suggested, an ideal method is
      still lacking because of high recurrence rates. METHODS: This prospective study
      was conducted in 63 patients who were treated with the use of a rhomboid excision
      and Limberg flap closure for sacrococcygeal pilonidal sinus. The follow-up period
      ranged from 4 to 52 months (mean, 25 months). RESULTS: The mean hospital stay was
      3 days (range, 2-7 days) and the mean time to return to work was 15 days (range,
      12-26 days). Early wound complications and recurrence were encountered in 6% and
      3%, respectively. Nineteen percent had numbness at the operation site and 63%
      were not pleased with cosmetic appearance of the scars. CONCLUSIONS: The results
      favor rhomboid excision and Limberg flap closure in the treatment of
      sacrococcygeal pilonidal sinus, especially in recurrent cases and in patients
      with extensive involvement. Low recurrence rates, shorter hospital stay, and time
      off from work may outweigh the disadvantages related to unfavorable cosmetic
      appearance.

PMID- 14639352
TI  - Visual-spatial ability correlates with efficiency of hand motion and successful
      surgical performance.
AB  - BACKGROUND: This study examines the influence of visual-spatial ability and
      manual dexterity on surgical performance across 3 levels of expertise. METHODS:
      Dental students, surgical residents, and staff surgeons completed standardized
      tests of manual dexterity and visual-spatial ability and were assessed
      objectively while performing the rigid fixation of an anterior mandible on bench
      model simulations. Outcome variables included expert assessment of technical
      performance and efficiency of hand motion during the procedure (recorded using
      electromagnetic sensors). RESULTS: Visual-spatial scores correlated significantly
      with surgical performance scores within the group of dental students (r=.40
      to.73), but this was not the case for residents or staff surgeons. For all
      groups, manual dexterity did not correlate with hand motion parameters. There
      were no differences between groups in visual-spatial ability or manual dexterity,
      but highly significant differences were seen in surgical performance scores
      (P<.001), in that surgeons outperformed residents, who in turn outperformed
      students. CONCLUSIONS: Among novices, visual-spatial ability is associated with
      skilled performance on a spatially complex surgical procedure. However, advanced
      trainees and experts do not score any higher on carefully selected visual-spatial
      tests, suggesting that practice and surgical experience may supplant the
      influence of visual-spatial ability over time. Thus, the use of these tests for
      the selection of residents is not currently recommended; they may be of more use
      in identifying those novice trainees (ie, those with lower test scores) who might
      benefit most from brief supplementary instruction on specific technical tasks.

PMID- 14639353
TI  - Laparoscopic-type environment enhances mesothelial cell fibrinolytic activity in
      vitro via a down-regulation of plasminogen activator inhibitor-1 activity.
AB  - BACKGROUND: Fewer intraperitoneal adhesions have been observed after laparoscopic
      surgery compared with conventional techniques. The aim of this study is to assess
      the effect of the pneumoperitoneum on mesothelial cell fibrinolytic activity by
      use of an in vitro model. METHODS: Human peritoneal mesothelial cells were seeded
      onto 24-well plates and incubated in carbon dioxide or helium at 5 mm Hg for 4
      hours or standard culture conditions. Supernatant was removed for analysis at 0,
      24, 48, and 72 hours after gas incubation and analyzed for plasminogen activator
      activity, total tissue plasminogen activator (tPA), and total plasminogen
      activator inhibitor-1 (PAI-1) concentrations by use of an enzyme-linked
      immunosorbent assay. The effect of different insufflation pressures (0, 7, and 14
      mm Hg) was also examined. RESULTS: Enhanced plasminogen activator activity was
      observed at 48 hours and 72 hours from cells exposed to CO(2) (P<.04 each) and
      helium (P<.05 each) compared with control. This was associated with a decrease in
      PAI-1 concentrations at 48 and 72 hours in both the CO(2) and helium groups
      compared with control (P<.03 each, CO(2) vs control; and P<.04 each, helium vs
      control). No changes in tPA levels were observed. Changes in insufflation
      pressures did not affect plasminogen activator activity. CONCLUSIONS: These
      results suggest that incubation of human mesothelial cells with both CO(2) and
      helium in the absence of oxygen enhances mesothelial cell fibrinolytic activity
      because of a reduction in PAI-1 concentrations. These changes may participate in
      the observed reduction in adhesions after laparoscopic surgery relative to open
      surgery.

PMID- 14639354
TI  - Duct-to-mucosa versus end-to-side pancreaticojejunostomy reconstruction after
      pancreaticoduodenectomy: results of a prospective randomized trial.
AB  - BACKGROUND: Anastomotic failure is still a significant problem that affects the
      outcome of pancreaticoduodenectomy. There have been many techniques proposed for
      the reconstruction of pancreatic digestive continuity, but there have been few
      prospective and randomized studies that compare their efficacy. METHODS: In the
      current work, 144 patients who underwent a pancreaticoduodenectomy with soft
      residual tissue were assigned randomly to receive either a duct-to-mucosa
      anastomosis (group A) or a 1-layer end-to-side pancreaticojejunostomy (group B).
      RESULTS: The 2 treatment groups were found not to have any differences in regards
      to vital statistics, underlying disease, or operative techniques. The
      postoperative course was complicated in 54% of the 144 patients, with a
      comprehensive incidence of abdominal complications in 36% (group A, 35%; group B,
      38%; P=not significant). The principal complication was pancreatic fistulas,
      which occurred in 14% of patients (group A, 13%; group B, 15%; P=not
      significant). Two patients (2%) required reoperation; the postoperative mortality
      rate was 1%. CONCLUSION: The 2 methods that were studied revealed no significant
      difference the rate of complications.

PMID- 14639356
TI  - Pancreatic cancer growth is inhibited by blockade of VEGF-RII.
AB  - BACKGROUND: Angiogenesis is important in the development and progression of
      pancreatic cancer. Therefore antiangiogenic therapy targeting endothelial cells
      may represent a promising therapeutic option. The aim of the study was to
      evaluate antiangiogenic therapy as a potential therapeutic option in pancreatic
      cancer. METHODS: Replication-deficient retroviruses encoding truncated VEGF-RII
      were used to block vascular endothelial growth factor (VEGF) signaling. Tumor
      growth of 3 pancreatic cancer cell lines was assayed in a nude mouse model in
      which each pancreatic cancer cell line was subcutaneously inoculated together
      with retrovirus-producing cells. Expression of VEGF was assayed by RT-PCR and by
      enzyme-linked immunosorbent assay. Oxygen tension in tumors was determined
      polarographically. RESULTS: All 3 pancreatic cancer cell lines expressed VEGF
      mRNA, with the highest VEGF secretion seen in MIA PaCa-2 cells. In vivo
      therapeutic intervention through dominant negative inhibition of VEGF-RII
      significantly reduced the growth rate of subcutaneous tumors and inhibited tumor
      neoangiogenesis. Tumor oxygenation, however, was not altered in xenograft tumors
      treated with dominant negative retroviruses. CONCLUSION: The ligand/receptor
      system consisting of VEGF and VEGF-RII seems to be of biologic significance in
      the pathogenesis of pancreatic cancer growth. Therefore therapeutic intervention
      in this angiogenic system by a retroviral-based gene transfer technology
      represents a rational and feasible new technique to inhibit tumor growth.

PMID- 14639357
TI  - Chronic extrinsic denervation of the small bowel: effect on adrenergic and
      cholinergic contractile mechanisms in canine ileal circular muscle.
AB  - BACKGROUND: Small bowel transplantation necessitates chronic extrinsic
      denervation and is often followed by enteric dysfunction. Our aim was to study
      canine ileal contractile activity after extrinsic denervation. METHODS: In vitro
      dose responses to cholinergic and adrenergic agonists were evaluated in canine
      ileal muscle strips in control subjects and after jejunoileal extrinsic
      denervation (EX DEN) at 0, 2, and 8 weeks after operative preparation. RESULTS:
      Spontaneous activity and the increased activity after tetrodotoxin (enteric nerve
      blockade) did not differ between groups. Response to acetylcholine and
      bethanechol did not differ at any time in the control or EX DEN group. In
      contrast, the EX DEN group demonstrated a procontractile hypersensitivity to
      norepinephrine at 2 and 8 weeks that was not seen in the control group. This
      adrenergic hypersensitivity in the EX DEN group was insensitive to intramural
      neural blockade with tetrodotoxin. CONCLUSIONS: Extrinsic denervation does not
      affect basal contractile activity, augmented contractile activity to intramural
      neural blockade, nor response to cholinergic agonists. However, it induces a
      procontractile adrenergic hypersensitivity in canine ileal circular muscle
      mediated at the level of the smooth muscle and not at the enteric nervous system.

PMID- 14639358
TI  - Detection of cancer cells in mesenteric vein and peripheral vessels by measuring
      telomerase activity in patients with colorectal cancer.
AB  - BACKGROUND: Liver metastasis is an important factor determining prognosis in
      colorectal cancer. The objective of this study was to assess whether colorectal
      cancer cells in the drainage veins can be detected by measuring telomerase
      activity and its detection is correlated with liver metastasis. METHODS:
      Telomeric repeat amplification protocol assay in combination with an
      immunomagnetic sorting was used for measuring telomerase activity of epithelial
      cells in blood samples collected from mesenteric (tumor-drainage) vein and
      peripheral vessels of 41 colorectal cancer patients. Telomerase activity was
      calculated as relative telomerase activity (RTA) against a control template and
      analyzed in terms of liver metastasis. RESULTS: RTA of mesenteric blood samples
      was significantly higher in patients with liver metastasis (60.8%; n=7) than in
      those without metastasis (19.7%; n=34; P=.019). The RTA of peripheral blood
      sample was also higher in patients with liver metastasis (26.8%) than in those
      without metastasis (11.1%; p=.17). Moreover, 57% of cases with liver metastasis
      exhibited a positive telomerase activity in mesenteric blood sample, whereas it
      was 18% in cases without metastasis. CONCLUSIONS: Our assay was proven to be a
      feasible method for detecting cancer cells in tumor-drainage veins. High
      telomerase activity of mesenteric blood samples reflected the existence of liver
      metastasis of colorectal cancer.

PMID- 14639359
TI  - Thoracic epidural anesthesia improves the gastric microcirculation during
      experimental gastric tube formation.
AB  - BACKGROUND: Gastric tube formation is a surgical technique to reestablish the
      continuity of the gastrointestinal tract after esophagectomy. Our aims were to
      study the microcirculatory consequences of experimental gastric tube formation
      and characterize the effects of thoracic epidural anesthesia (TEA) during this
      condition. METHODS: The experiments were performed on mongrel dogs anesthetized
      with pentobarbital. The stomach was prepared for replacement according to the
      method of Akiyama, and TEA was induced with bupivacaine (1 mg/kg).
      Macrohemodynamics, intramucosal pH, and gastric motility changes were monitored,
      and intravital video-microscopy with orthogonal polarization spectral imaging
      technique was used to observe the gastric microcirculation. RESULTS: The gastric
      pull-up induced a significant decrease in intramucosal pH. The functional
      capillary density of the mucosa or subserosa did not change; the red blood cell
      velocity in the capillaries of the upper part of the gastric tube was decreased
      in the mucosa, as well as on the serosal side. After epidural anesthesia the red
      blood cell velocity returned to the baseline, and the gastric and intestinal
      motility index was significantly increased. CONCLUSIONS: TEA significantly
      improves the microcirculation of the distal portion of the gastric tube and
      increases the intestinal and gastric motility after gastric pull-up. The
      procedure is favorable and should be recommended during reconstructive esophageal
      surgery.

PMID- 14639360
TI  - Decrease in core liver temperature with 10 degrees C by in situ hypothermic
      perfusion under total hepatic vascular exclusion reduces liver ischemia and
      reperfusion injury during partial hepatectomy in pigs.
AB  - OBJECTIVE: We attempted to assess liver ischemia/reperfusion injury under a mild
      decrease in core liver temperature of 10 degrees C by in situ hypothermic
      perfusion during ischemia. METHODS: Liver ischemia was induced in pigs by total
      hepatic vascular exclusion with concomitant in situ perfusion with hypothermic (4
      degrees C) Ringer-glucose (cold perfused group, core liver temperature maintained
      at 28 degrees C), with normothermic (38 degrees C) Ringer-glucose (warm perfused
      group) or without in situ perfusion (control group). RESULTS: In the cold
      perfused, warm perfused, and control groups, 24-hour survival was 5/5, 0/5, and
      3/5, respectively. Hemodynamic parameters in the cold perfused group remained
      stable, whereas pigs in both other groups required circulatory support. Plasma
      AST and interleukin-6 levels were lower in the cold perfused group than in both
      other groups. Hepatocellular function was best preserved in the cold perfused
      group as indicated by complete recovery of bile production during reperfusion and
      no loss of indocyanine green clearance capacity. In both other groups, bile
      production and indocyanine green clearance capacity were reduced significantly.
      The hyaluronic acid uptake capacity of pigs in the cold perfused group or control
      group did not differ, indicating preserved sinusoidal endothelial cell function.
      Histopathologic injury scores during reperfusion were significantly lower in the
      cold perfused group when compared to both other groups. CONCLUSIONS: A mild
      decrease in core liver temperature of 10 degrees C by in situ hypothermic liver
      perfusion during ischemia protects the liver from ischemia/reperfusion injury.
      This protection appears to be related to cooling of the liver rather than to the
      washout of blood during perfusion.

PMID- 14639361
TI  - Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat:
      involvement of superoxide and tumor necrosis factor-alpha from hepatic
      macrophages.
AB  - BACKGROUND: The objective of this study was to investigate the effects of OPC
      6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver
      injury in the rat. METHODS: P. acnes was administered intravenously to the rat at
      16 mg/kg 7 days before the experiments. In liver perfusion experiments,
      lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL. The
      chemiluminescence method and histochemical reduction of nitro blue tetrazolium
      were used for detecting superoxide. Release of cytokines into the perfusate was
      examined. In in vivo experiments, lipopolysaccharide was administered
      intravenously to the rat at 200 microg/kg. Concentrations of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were
      determined in the plasma, and myeloperoxidase activity was measured in the liver
      tissue. OPC-6535 was given intravenously at 1 mg/kg 30 minutes before
      lipopolysaccharide challenge, and was then, in perfusion experiments, added to
      the buffer at 10 micromol/L. RESULTS: In perfusion experiments, P. acnes and
      lipopolysaccharide caused dramatic production of superoxide, tumor necrosis
      factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil
      chemoattractant-1 (GRO/CINC-1). Superoxide was mainly from hepatic macrophages.
      Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect
      GRO/CINC-1. In in vivo experiments, P. acnes and lipopolysaccharide increased the
      level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase
      activity in the liver. OPC-6535 reduced TNF-alpha, AST, and ALT, but did not
      affect GRO/CINC-1 or myeloperoxidase. CONCLUSION: Attenuation of liver injury by
      OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF
      alpha production by hepatic macrophages in P. acnes- and lipopolysaccharide
      treated rats.

PMID- 14639362
TI  - The immunophenotype and activation status of the lymphocytic infiltrate in human
      breast cancers, the role of the major histocompatibility complex in cell-mediated
      immune mechanisms, and their association with prognostic indicators.
AB  - BACKGROUND: The aims of this study were to characterize, phenotypically, the
      immune infiltrate in human breast cancers, to assess the activation status of
      tumor-infiltrating lymphocytes (TIL), and to define the association of these
      findings with established prognostic indicators. METHODS: Immunohistochemistry
      was performed on frozen sections of 60 primary breast cancers by use of
      monoclonal antibodies to T lymphocytes (CD3), T-helper cells (CD4), cytotoxic T
      cells (CD8), natural killer cells (CD56), interleukin-2 receptors (IL-2R), and
      major histocompatibility (MHC) class I antigen (HLA-ABC) and MHC class II antigen
      (HLA-DR). RESULTS: All tumors stained positive for CD3, CD4 and CD8, but with
      marked variation in the intensity of the infiltrate. In tumors with a moderate
      infiltrate of TIL, there was a trend toward a greater representation of T-helper
      cells. However, as the intensity of TIL increased, there was a decline in the
      proportion of T-helper cells and a concomitant rise in the relative proportion of
      cytotoxic T cells. There was a relative paucity of natural killer cells. A
      significant association was found between the intensity of TIL and the number of
      positive nodes (P=.02) and the intensity of the infiltrate of both T-helper cells
      and cytotoxic T cells with ER expression (P=.03 and.05, respectively). Most
      tumors stained positive for IL-2R. The expression of IL-2R was associated with
      the intensity of TIL (P<.0001), T-helper cells (P<.002), cytotoxic T cells
      (P=.01) and natural killer cells (P=0.04), and also with the degree of lymph node
      positivity (P=.02) and histologic tumor grade (P=.05). MHC class II expression
      was variable, and a large proportion of the tumors showed limited expression in
      individual cancer cells. There was an association between the expression of HLA
      DR in tumor cells and the activation status of TIL (P=.03). CONCLUSION: An immune
      infiltrate is an invariable finding in breast cancers, and the intensity of the
      infiltrate is greater in node positive tumors. Additionally, TIL may well be
      activated, albeit partially, in most tumors, suggesting that cell-mediated immune
      mechanisms are functionally intact.

PMID- 14639364
TI  - Liver resection in patients with Gilbert's syndrome.

PMID- 14639365
TI  - Future surgeon meets the James-Younger gang.

PMID- 14639366
TI  - Superior mesenteric artery syndrome presenting with acute massive gastric
      dilatation, gastric wall pneumatosis, and portal venous gas.

PMID- 14639375
TI  - Tropical dermatology: viral tropical diseases.
AB  - Viruses are important pathogens in tropical areas; most of them, especially the
      tropical hemorrhagic fevers, produce mucocutaneous manifestations. More than any
      other kind of pathogen, viruses have the possibility for being widespread, since
      they have a greater probability of mutation than do bacteria, can cross species
      barriers easily, and infect both human beings and animals in habitats with a
      great biodiversity. Tropical habitats also have been subject to major ecologic
      changes in the last few decades, exposing humans to direct contact with these
      viruses and allowing hemorrhagic fevers due to new emergent viruses such as
      flaviviruses, filoviruses, arenaviruses, and hantaviruses to become major threats
      to public health. The collapse of eradication programs in many countries, as well
      as population increases and ecologic modifications, have led to the spread of
      dengue and yellow fever to large portions of the world owing to the dissemination
      of vectors, especially mosquitoes, with broad ecologic ranges. Viruses previously
      restricted to some geographic areas, such as Rift Valley fever, Crimean-Congo
      hemorrhagic fever, West Nile fever, and monkeypox are now affecting new countries
      and populations. Other viruses such as herpes B infection often affect travelers
      and animal handlers in most parts of the world. Dermatologic lesions occur in all
      these diseases and can facilitate a rapid diagnosis, leading to control of the
      virus and helping prevent possible outbreaks.

PMID- 14639376
TI  - Specific site involvement in fixed drug eruption.
AB  - A total of 105 patients with established fixed drug eruption (FDE) by oral
      provocation were evaluated with regard to a drug-related site involvement.
      Cotrimoxazole was the leading causative agent (63.8%), followed by naproxen
      sodium (23.8%), dipyrone (5.7%), oxicams (4.8%) and other rare causes (1.9%).
      Cotrimoxazole most frequently induced lesions on genital mucosa; naproxen and
      oxicams on lips; and dipyrone on trunk and extremities. Isolated FDE on male
      genitalia (n = 16) was exclusively because of cotrimoxazole. A highly significant
      association could be established between naproxen and FDE on lips (chi-square =
      28.3; corrected P =.000002). As this study represents the largest series of
      patients with naproxen-induced FDE, we would suggest that naproxen should be
      considered as an important potential cause of FDE on lips.

PMID- 14639377
TI  - Anetoderma and its prothrombotic abnormalities.
AB  - BACKGROUND: Anetoderma is characterized by circumscribed areas of flaccid skin
      due to the loss of elastic tissue in the dermis. It may be primary or secondary
      to various dermatoses. The primary form has been reported in association with
      autoimmune diseases and recently with antiphospholipid antibodies. Its etiology
      remains unknown. OBJECTIVES: To analyze clinical and laboratory data from a
      series of patients with anetoderma referred in our university reference center
      for connective tissue disorders. PATIENTS AND METHODS: All the consecutive
      patients with histologically confirmed anetoderma followed in our clinic from
      1996 to 2001 were enrolled in this study. Laboratory investigations included the
      screening for prothrombotic abnormalities and classical immunological
      investigations for systemic lupus erythematosus. Clinical and laboratory data
      were analyzed retrospectively. RESULTS: Anetoderma was primary in 9 cases and
      secondary to lupus profundus in 2 cases. Prothrombotic abnormalities were
      detected in 10 patients (9/9 with primary and 1/2 with secondary anetoderma).
      Antiphospholipid antibodies were detected in 9 patients. Only 4 patients
      fulfilled criteria for definite antiphospholipid syndrome which was primary for 3
      and associated with systemic lupus erythematosus in the other. CONCLUSION:
      Patients with anetoderma should be evaluated for the possible presence of a
      prothrombotic state and warned of its potential risks when present.

PMID- 14639378
TI  - Restoration of hair growth with topical diphencyprone in mouse and rat models of
      alopecia areata.
AB  - BACKGROUND: The contact sensitizer, diphencyprone (DPCP), is one of the most
      effective therapies for the more severe forms of alopecia areata (AA). OBJECTIVE:
      The purpose of this study was to determine the efficacy of topical DPCP on the 2
      available rodent models for AA, and to determine the underlying therapeutic
      mechanisms. METHODS: AA-affected mice and rats were treated unilaterally with
      topical DPCP on the ventral and dorsal surface, respectively. The opposite sides
      were treated with vehicle alone. Skin biopsy specimens were collected from both
      sides for histologic analysis. RESULTS: Hair regrowth was observed on the treated
      sides in the majority of the animals of both species. Immunohistochemical
      analyses revealed reduction of intrafollicular CD8(+) lymphocyte infiltrates
      after successful treatment in mice. CONCLUSION: The AA-like hair disorder of
      these 2 rodent models can be used as a tool for furthering our understanding of
      human AA and the therapeutic actions of DPCP.

PMID- 14639379
TI  - Eruptive melanocytic nevi in patients with renal allografts: report of 10 cases
      with dermoscopic findings.
AB  - Eruptive nevi have been reported after renal allograft transplantation,
      particularly in children and adolescents, and immunosuppression has been
      suggested to favor both benign and malignant melanocyte proliferation. In this
      study, we describe the dermoscopic features of eruptive melanocytic nevi in 10
      children, adolescents, and young adults with renal allografts in whom multiple
      melanocytic nevi developed during a short period after transplantation.
      Dermoscopy of the eruptive pigmented lesions revealed a peripheral rim of brown
      globules. This rim of peripheral globules was present in 80% of the patients with
      eruptive nevi and in most of the lesions of the same patient. The other standard
      dermoscopic criteria for melanocytic nevi were normal. In our study, we confirm
      previous reports concerning the development of eruptive nevi in children and
      adolescents receiving immunosuppressive therapies. In particular, we showed by
      dermoscopy the presence of a characteristic symmetrical rim of peripheral brown
      globules. This finding is consistent with the hypothesis that a symmetrical
      peripheral rim of globules may indicate rapid enlargement of melanocytic lesions.
      Moreover, we have identified a new group of patients characterized by this
      dermoscopic feature. These patients are children, adolescents, and young adults
      with renal allografts receiving immunosuppressive therapy and it is plausible
      that this dermoscopic characteristic may be found in eruptive nevi developed in
      association with immunosuppression from any cause.

PMID- 14639380
TI  - Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in
      paraneoplastic pemphigus.
AB  - BACKGROUND: Pemphigus vulgaris (PV) shows autoimmune reaction against desmoglein
      3 (Dsg3), whereas paraneoplastic pemphigus (PNP) shows autoimmune reaction
      against Dsg3 as well as numerous members of the plakin family. It has been
      demonstrated that in PV, dominant epitopes reside in N-terminal adhesive regions
      of Dsg3 and that the dominant IgG subclass against Dsg3 is IgG4. OBJECTIVE: We
      attempted to map conformational epitopes and analyze IgG subclass distribution
      against Dsg3 in PNP. METHOD: Epitopes on Dsg3 for circulating IgG autoantibodies
      from PNP (n = 22) were studied with competition enzyme-linked immunosorbent assay
      (ELISA) using domain-swapped molecules between Dsg3 and Dsg1 and were compared
      with those for IgG autoantibodies from PV (n = 22). IgG subclass distribution was
      analyzed with PNP serum by Dsg3 ELISA (n = 17). RESULTS: Epitopes on Dsg3 in PNP
      were distributed more broadly through the extracellular domain of Dsg3 than were
      those in PV, although the N-terminal extracellular domains of Dsg3 were more
      frequently recognized than the C-terminal extracellular domains. IgG subclass in
      PNP was IgG1 and IgG2 dominant. CONCLUSION: Autoimmune response against Dsg3 in
      PNP is more diversified than that in PV, a finding that suggests PNP and PV have
      different pathophysiologic mechanisms for triggering production of anti-Dsg3 IgG.

PMID- 14639381
TI  - Annular lichenoid dermatitis of youth.
AB  - BACKGROUND: Lichenoid dermatoses are composed of a wide spectrum of disorders
      with a common histopathologic interface pattern but diverse causes and
      pathophysiology. OBJECTIVE: We describe a series of young patients with a
      peculiar annular lichenoid dermatitis, the clinical appearance of which initially
      suggested diagnoses of morphea, mycosis fungoides, or annular erythema. RESULTS:
      The study involved 23 patients (median age 10 years; age range 5-22 years).
      Lesions consisted of persistent asymptomatic erythematous macules and round
      annular patches with a red-brownish border and central hypopigmentation, mostly
      distributed on the groin and flanks. Histology revealed a peculiar lichenoid
      dermatitis with massive necrosis/apoptosis of the keratinocytes limited to the
      tips of rete ridges, in the absence of dermal sclerosis and epidermotropism of
      atypical lymphocytes. The infiltrate was composed mainly of memory CD4(+) CD30(-)
      T cells with few B cells and macrophages. Analysis of T-cell receptor-gamma-chain
      gene rearrangement in skin biopsy specimens revealed polyclonality in all the 15
      cases studied. Topical and systemic corticosteroids or phototherapy were
      effective in most patients with relapse after treatment withdrawal. CONCLUSIONS:
      We suggest that this is a distinctive inflammatory condition, and we propose to
      term it "annular lichenoid dermatitis of youth."

PMID- 14639382
TI  - Quality of life in patients with allergic contact dermatitis.
AB  - BACKGROUND: Allergic contact dermatitis (ACD), a common dermatological disorder,
      often results in ongoing disease and disability. However, relatively little has
      been published quantifying the quality of life (QoL) of patients with ACD.
      OBJECTIVES: This study was conducted to investigate the impact of ACD on QoL and
      explore prognostic factors that influence outcomes. METHODS: A total of 428
      subjects with ACD were, at varying times after diagnosis, mailed a QoL
      questionnaire modified from Skindex-16 to include an additional 5 items
      pertaining to occupational impact. The QoL scores were correlated with subject
      demographics, disease characteristics, and management techniques to ascertain
      factors that impact QoL in subjects with ACD. RESULTS: The response rate was 35%,
      with 149 subjects returning the postal survey. Responders reported being bothered
      most by itching, skin irritation, and persistence of the condition. Of the four
      scales included in the QoL questionnaire, the emotions scale had the worst
      composite QoL score, followed by symptoms, functioning, and occupational impact.
      Patients with ACD of the face were significantly more bothered by the appearance
      of their skin. Hand involvement and occupationally related ACD were associated
      with worse QoL scores within the occupational impact and functioning scales.
      Subjects that had changed jobs because of ACD had more severe QoL impairment than
      any other group analyzed, with significantly worse scores on 17 of the 21 QoL
      items. A history of atopic eczema seemed to impart improved outcomes on patients
      with ACD, and these subjects were less worried about being fired from their jobs.
      Subjects diagnosed by patch testing more than 36 months after disease onset
      seemed to have worse QoL scores than those diagnosed earlier in the natural
      history of the disease. Patients diagnosed by patch testing within the last 6
      months had the worst QoL scores, while the best outcomes were reported in
      subjects patch tested 6 to 12 months ago. A slight decline in QoL was observed 12
      months after patch testing, but scores did not diminish back to the level seen
      immediately after diagnosis. CONCLUSIONS: ACD has an appreciable effect on QoL,
      especially when it affects the hands, the face, or is occupationally related. Of
      the four scales included in our study, the emotions scale suffered the greatest
      effect. Emotional impact is therefore an important measure of QoL in ACD
      patients. Outcomes in patients with ACD were improved by early diagnosis and
      subjects enjoyed their best QoL at 6 to 12 months after patch testing. However,
      individuals who elected to change jobs because of their skin condition reported
      significantly worse QoL than those who retained their current positions.

PMID- 14639383
TI  - CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in
      lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma.
AB  - BACKGROUND: CD30+ cutaneous lymphoproliferative disorders (CLPDs) include
      lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous
      anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have
      an excellent prognosis. OBJECTIVE: We sought to present the single-center
      experience of Stanford University, Stanford, Calif, in the management of
      CD30+CLPDs. METHODS: A retrospective cohort analysis of 56 patients with
      CD30+CLPDs treated at our institution was performed. RESULTS: No patients with
      lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10
      years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease
      specific survival at 5 years for localized versus generalized PCALCL was 91%
      versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse
      rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease.
      No clinical or histologic factors analyzed were predictive of worse outcome in
      lymphomatoid papulosis and PCALCL. CONCLUSION: Similar to prior reports from
      multicenter European groups, the single-center experience at our institution
      demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of
      PCALCL with poor outcome do exist.

PMID- 14639384
TI  - Differences and similarities among expert opinions on the diagnosis and treatment
      of pemphigus vulgaris.
AB  - BACKGROUND: As a result of a lack of large-scale controlled studies, the
      diagnosis and management of pemphigus vulgaris (PV) has been solely on the basis
      of expert opinion, rather than on empirical evidence. We have completed a survey
      of worldwide experts on the diagnostic and therapeutic approaches to PV. METHODS:
      We conducted a telephone-based survey of 24 physicians from academic, tertiary
      care centers worldwide with an average of 20 years experience treating pemphigus.
      Survey questions included referral patterns, diagnostic techniques, and
      therapeutic regimens. RESULTS: Of those surveyed, 50% receive referrals within 6
      months after onset of symptoms, 17% within 1 year, and 8% within 3 years.
      Diagnosis is secured by 96% using skin biopsy specimen with direct
      immunofluorescence, and by indirect immunofluorescence alone for 4%. None of the
      participating physicians make the diagnosis of PV solely on clinical and
      histologic evidence. Of the physicians, 75% initially treat with prednisone and
      25% use other agents or attempt to eliminate potential triggers. The physicians
      who initially used noncorticosteroid drugs did so with no relation to the nature
      or extent of the disease. Of those surveyed, 50% use prednisone doses of 1
      mg/kg/d, 31% use 1 to 1.5 mg/kg/d, and 19% use 1.5 to 3 mg/kg/d. Azathioprine is
      used as an adjuvant by 44%, mycophenolate mofetil by 20%, cyclophosphamide by
      16%, and methotrexate by 8%. Complete discontinuation of prednisone was the goal
      for 37% whereas others were satisfied with doses from 2.5 to 10 mg/d. CONCLUSION:
      Wide variation exists in diagnostic techniques and treatment of PV, even among
      the world's experts. The lag time from symptom onset to referral emphasizes the
      need for heightened awareness. There is clearly a need for consensus standards
      with regard to patient stratification and randomized controlled trials.

PMID- 14639385
TI  - Treatment of severe lichen planus with mycophenolate mofetil.
AB  - Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical
      appearances. The treatment of disseminated and especially erosive forms of LP is
      often difficult and disappointing. Activated T cells are important in the
      pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to
      keratinocyte destruction and lesion formation. Similar histologic findings are
      present in graft-versus-host disease. Since T cells are key players in the
      development of both disorders and mycophenolate mofetil has been successfully
      introduced in the treatment of graft-versus-host disease, we have examined the
      therapeutic potential of this agent in 3 patients suffering from disseminated and
      erosive LP. Mycophenolate mofetil was well tolerated and induced complete
      remission in 2 patients, and substantial improvement in the third patient.

PMID- 14639386
TI  - Basaloid follicular hamartomas associated with autoimmune disease: a possible
      role for retinoids in therapy.
AB  - A basaloid follicular hamartoma (BFH) may be localized or diffuse. It may also be
      congenital or acquired. Development of diffuse BFHs has been associated with
      autoimmune disease and with the development of diffuse alopecia. Two women with
      autoimmune diseases had diffuse alopecia develop. We present the histologic
      features of BFH seen in these 2 women using vertical and transverse sections, and
      the response of 1 patient to retinoid therapy. Histologic sections showed a
      hamartomatous proliferation of hair follicles involving the majority of their
      hairs. The hamartomatous follicles showed variable degrees of hair
      differentiation. One patient, treated with oral and then topical retinoids,
      showed a partial regrowth of scalp hair and some regression of the cutaneous
      nodules. Increased sonic hedgehog signaling pathways with increased Gli-1
      transcription has been shown to be present in the spectrum of follicular
      hamartomatous changes seen in BFHs. This may explain the response of one patient
      to retinoid therapy, because retinoids decrease Gli-1 transcriptional activity.

PMID- 14639387
TI  - Permanent hair removal with a diode-pumped Nd:YAG laser: a pilot study using the
      direct insertion method.
AB  - BACKGROUND: The removal of unwanted hair with various laser systems and related
      procedures has been investigated for many years. All researchers have met
      difficulty when trying to achieve "permanent" hair removal. In addition, damage
      to the epidermis and other complications, including hyper- or hypopigmentation in
      pigmented skin, have occurred because the laser energy was applied indirectly to
      the hair bulb through the epidermis. OBJECTIVE: To achieve permanent hair removal
      with the use of a diode-pumped neodymium:yttrium-aluminum-garnet laser system
      with an insulated optical needle. Also, to establish laser treatment parameters
      that allow for quick and effective removal of hair with minimal pain and no long
      term medical complications. METHOD: The laser used in the study was capable of
      producing up to 500 mJ of energy per burst at a 1,064-nm wavelength. A pulse
      width of 200-500 micros and a burst frequency of 100-200 Hz could be selected,
      and both defined a subset of the treatment parameter space. An optical needle,
      typically 130 microm in diameter, was prepared before each new treatment was
      conducted. Three bursts of energy, 300 mJ each, with a 300-millisecond interval,
      were delivered through the optical needle into each hair follicle. Between 200
      and 300 shin hairs, typically terminal hairs, on each of 5 volunteers were
      treated. These volunteers were observed over 18.5-30 months for the regrowth of
      hairs by hair count. RESULTS: At the end of the observation period (6-30 months
      after the last treatment), 3 of 5 volunteers showed permanent loss of 76%-94.3%
      of their unwanted hair. One volunteer lost 34.8% of the original hair, but
      regrown hair was much thinner than the original terminal hair. One volunteer lost
      only 22.8% of the original hair, and regrown hair was coarse terminal hair.
      Except for the loss of hair, no change in skin texture, sensation, or skin color
      was observed. CONCLUSION: The direct insertion optical method (DIOM), delivering
      laser energy directly to the hair bulb through an optical needle, has proven to
      be effective and achieves permanent hair removal in 60% of volunteers without
      medical complications.

PMID- 14639388
TI  - Lack of specificity in skin biopsy specimens to assess for acute graft-versus
      host disease in initial 3 weeks after bone-marrow transplantation.
AB  - Acute graft-versus-host disease is a serious and common complication after
      allogeneic bone-marrow transplantation, occurring in more than 20% of HLA antigen
      identical sibling transplants and unrelated donor transplants. Bone-marrow
      transplantation is considered standard therapy for several hematologic
      malignancies and several nonhematologic disorders. In this retrospective study,
      we searched our institutional dermatopathology database between January 1998 and
      November 2002 for patients in whom skin biopsy specimens were examined less than
      3 weeks after bone-marrow transplantation. A total of 40 slides from 38 patients
      were examined for the presence of the histologic features characteristic of acute
      graft-versus-host disease. Specimens of skin biopsies examined in the study
      varied from 3 to 21 days, with a mean of 12 days, status post-bone-marrow
      transplantation. The histologic findings of the 40 slides we examined were
      nonspecific and could be accounted for by a number of diagnoses. In summary, we
      propose that skin biopsies need not be preformed before 3 weeks status post-bone
      marrow transplantation if the sole purpose is to rule out acute graft-versus-host
      disease.

PMID- 14639389
TI  - Nail-patella syndrome.

PMID- 14639390
TI  - Consensus conference on pediatric atopic dermatitis.

PMID- 14639391
TI  - The evolution of current medical and popular attitudes toward ultraviolet light
      exposure: part 3.
AB  - In the 1930s, attitudes toward ultraviolet (UV) light exposure began to change
      significantly within the medical profession. UV radiation had been promoted as
      healthful since the century's start, and particularly after the discovery of its
      role in vitamin-D metabolism. Increasingly, however, attention would focus on the
      risks of UV light exposure from sunlamps and sunbathing. During this time, the
      American Medical Association established guidelines for the approval of UV lamps
      and the appropriate therapeutic uses of phototherapy. The landmark experiments of
      Findlay and other researchers, in which malignant skin tumors were induced in
      rodents after exposure to UV lamps or sunlight, would lead to widespread
      recognition of the carcinogenicity of UV radiation. The role of sunlight in the
      etiology of skin cancer was increasingly mentioned in articles in popular
      magazines in the 1940s and 1950s. There was rapid growth of the sunscreen
      industry as well, although product efficacy remained highly variable. In the
      1950s, interest developed in the use of 8-methoxypsoralen ("the suntan pill") and
      dihyroxyacetone ("suntan in a bottle"). In spite of the known risks of UV
      exposure and attempts by physicians and other health professionals to educate the
      public and modify behavior, suntanning has remained tenaciously popular. Today,
      excessive UV light exposure is recognized as the major cause of the approximately
      1.3 million cases of skin cancer in the United States each year.

PMID- 14639392
TI  - Surgical Pearl: Temporary suspension suture (Frost suture) to help prevent
      ectropion after infraorbital reconstruction.

PMID- 14639393
TI  - A new cutaneous sign of mercury poisoning?
AB  - Chronic mercury poisoning is becoming a health concern because of extensive
      pollution of water and fish, and the increasing consumption of fish in the human
      diet. Mercury is extremely toxic to the body, especially the central nervous
      system, but diagnosis is difficult because of the lack of specific signs. A total
      of 11 patients were observed to have a nonpruritic or mildly pruritic discreet
      papular and papulovesicular eruption that correlated with high blood mercury
      levels. The mercury evidently came from increased seafood consumption. All of the
      patients improved when they were placed on either a seafood-free diet or
      chelation therapy. Physicians should suspect mercury poisoning in patients who
      eat a high-seafood diet who present with an asymptomatic or mildly pruritic
      papular or papulovesicular eruption.

PMID- 14639394
TI  - Daily UVB exposure levels in high-school students measured with digital
      dosimeters.
AB  - UV radiation exposure increases skin cancer risk. A substantial portion of a
      person's UV exposure occurs before the age of 18 years. We sought to determine
      UVB radiation exposure levels in high-school students during normal daily
      activity. Digital dosimeters were worn by 4 high-school students during 11 school
      days. Students were subjected to daily erythemal and suberythemal doses of UVB
      radiation. Programs to educate high-school students in sun-protective practices
      even during regular school activities are needed.

PMID- 14639395
TI  - Cutaneous lymphadenoma.
AB  - Cutaneous lymphadenoma is a rare tumor with distinctive histologic features. This
      entity was originally described as lymphoepithelial tumor by Santa Cruz and Barr
      in 1987. It was renamed cutaneous lymphadenoma in 1991. To date, at least 31
      cases of this entity have been reported. The literature did not contain a
      clinical photograph of this lesion. A case of this rare tumor is described that
      includes clinical and histologic features. The literature regarding the unclear
      histogenesis of this distinctive tumor is reviewed. This report is one of a only
      few clinical illustrations of cutaneous lymphadenoma. Consistent with previous
      reports, the histologic findings in this case include basaloid proliferation and
      intraepithelial lymphocytes. The usual initial clinical diagnosis is basal cell
      carcinoma localized mainly to the head and neck area. The incidence is
      approximately equal in male and female patients. Excision of this benign neoplasm
      is curative. Controversy exists regarding the histogenesis of this tumor.

PMID- 14639396
TI  - Contact orofacial granulomatosis caused by delayed hypersensitivity to gold and
      mercury.
AB  - Orofacial granulomatosis, an entity with characteristic clinicopathologic
      features, is thought to be a reactive process. The authors describe orofacial
      granulomatosis associated with contact allergy to gold in dental crowns in one
      patient and a possible allergic contact reaction to mercury from dental fillings
      in another one. Thus allergic contact dermatitis to the metals gold and mercury
      should be considered as a possible etiologic agent of orofacial granulomatosis.

PMID- 14639397
TI  - Hiccups, eructation, and other uncommon prodromal manifestations of herpes
      zoster.
AB  - Although the most frequent presentation of herpes zoster involves sensory
      neurons, motor and autonomic symptomatology is also known to occur in this
      disease. An unusual symptom of hiccups is described here. Other infrequent
      manifestations of this common illness, including the Ramsay Hunt syndrome, herpes
      zoster ophthalmicus, urinary and fecal retention, sexual dysfunction, and zoster
      sine herpete, are reviewed. Greater awareness of unusual presentations of herpes
      zoster is necessary for proper diagnosis and timely management of complications
      that may otherwise lead to disability and serious long-term sequelae.

PMID- 14639398
TI  - Multicentric reticulohistiocytosis with pulmonary involvement.
AB  - Multicentric reticulohistiocytosis (MRH) is a rare and possibly devastating
      systemic disorder characterized by tissue infiltration by histiocytes and
      multinucleated giant cells. The disease commonly involves the skin, joints, and
      mucous membranes, with the rare involvement of other organ systems. We describe a
      patient with MRH presenting with papules and nodules on both hands and a rapidly
      progressive arthritis who may have had pulmonary involvement of the disease.

PMID- 14639399
TI  - Exogenous lipoid pneumonia caused by facial application of petrolatum.
AB  - Exogenous lipoid pneumonia is a well-described entity in the literature. To our
      knowledge, this is the first reported case that occurred secondary to external
      application of petrolatum to the face for erythrodermic psoriasis.

PMID- 14639400
TI  - A unique presentation of calcinosis cutis in a patient with cystic fibrosis after
      double lung transplants.
AB  - Calcinosis cutis is the deposition of insoluble calcium salts in the skin and
      subcutaneous tissue. We report the case of a 28-year-old Caucasian woman with
      cystic fibrosis in whom strikingly symmetrical and reticulate calcinosis cutis
      developed on the lower extremities, which was noted on histology to spare the
      eccrine glands. Careful review of the literature fails to reveal any previous
      report with these remarkable cutaneous and histologic manifestations.

PMID- 14639401
TI  - Vesiculobullous dermatomyositis with panniculitis without muscle disease.
AB  - Vesicles and bullae formation is rare in dermatomyositis. We describe a 60-year
      old woman who presented with vesiculobullous dermatomyositis with panniculitis
      and no muscle disease.

PMID- 14639402
TI  - Pedunculated presentation of dermatofibrosarcoma protuberans.
AB  - A 26-year-old patient had a dermatofibrosarcoma protuberans that clinically was
      considered to represent either a skin tag or neurofibroma. Histopathologically,
      this lesion could easily have been misinterpreted as a neurofibroma, particularly
      in the context of the clinical findings.

PMID- 14639403
TI  - Febrile ulceronecrotic Mucha-Habermann's disease managed with methylprednisolone
      semipulse and subsequent methotrexate therapies.
AB  - Febrile ulceronecrotic Mucha-Habermann's disease is an unusual severe form of
      pityriasis lichenoides et varioliformis acuta characterized by abrupt onset of
      ulceronecrotic eruption associated with a high fever and systemic symptoms. To
      our knowledge, 19 cases of this disease have been reported in the literature, and
      4 of them were fatal. We report the case of a 12-year-old boy with this disorder
      who had abdominal pain, hypoproteinemia, and anemia. Although these associated
      symptoms are considered life-threatening factors according to reported cases, our
      patient was successfully treated with methylprednisolone semipulse and subsequent
      methotrexate therapies. From a review of the literature and the present case, we
      propose that when patients have these systemic symptoms, therapeutic choices
      include methotrexate, high-dose corticosteroids, and 4,4-diamino-diphenyl
      sulfone, which may depress early development of this disease.

PMID- 14639404
TI  - Segmented heterochromia in scalp hair.
AB  - Segmented heterochromia of scalp hair is characterized by the irregularly
      alternating segmentation of hair into dark and light bands and is known to be
      associated with iron deficiency anemia. The authors report the case of an 11-year
      old boy with segmented heterochromia associated with iron deficiency anemia.
      After 11 months of iron replacement, the boy's segmented heterochromic hair
      recovered completely.

PMID- 14639405
TI  - Placental metastasis of maternal melanoma.
AB  - Metastasis of maternal malignant tumor to the products of conception is a rare
      event. Melanoma is the most common maternal malignant tumor to metastasize to the
      placenta and the fetus. We report the case of a 28-year-old woman with melanoma
      during pregnancy. At parturition, histologic evaluation of the placenta revealed
      metastatic melanoma, and multiple organ metastasis developed. The infant was free
      of disease. Metastasis to products of conception portends a poor prognosis for
      the mother. To our knowledge, this report is the first of a patient with melanoma
      metastasis to the placenta to survive more than 7 months after parturition. As
      caretakers of patients with melanoma, dermatologists are in a position to
      coordinate and direct the care and follow-up treatment of affected patients.

PMID- 14639406
TI  - Axillary polymastia.
AB  - "Polymastia" is a term used to describe the presence of more than 2 breasts in
      human beings. It is synonymous with supernumerary or accessory breast tissue.
      Accessory breast tissue has the potential to undergo the same benign and
      malignant changes as normal pectoral breast tissue.

PMID- 14639407
TI  - Epidermolysis bullosa acquisita-like reaction associated with penicillamine
      therapy for sclerodermatous graft-versus-host disease.
AB  - A case of a bullous eruption occurred in a patient being treated with
      penicillamine for sclerodermatous graft-versus-host disease following bone marrow
      transplantation. After 7 days of treatment with 150 mg penicillamine, a painful
      bullous eruption with accompanying purpuric lesions suddenly developed in
      previous sclerodermatous infiltrations. A diagnosis of epidermolysis bullosa
      acquisita-like eruption was made, and the patient was treated with drug
      withdrawal and administration of cyclosporine and methylprednisolone.
      Epidermolysis bullosa acquisita-like reaction is an extremely rare cutaneous side
      effect of penicillamine. The surprisingly early onset of this eruption in lesions
      of sclerodermatous graft-versus-host disease might have been due to severe immune
      alteration.

PMID- 14639408
TI  - Cutaneous lymphoplasmacytoid lymphoma (immunocytoma) with Waldenstrom's
      macroglobulinemia mimicking rosacea.
AB  - A 50-year-old woman presented with a 2-year history of facial lesions that were
      resistant to rosacea therapy. Evaluation of histology, immunohistochemistry, gene
      rearrangement study, bone-marrow biopsy specimen, and systemic workup revealed
      the findings of lymphoplasmacytoid lymphoma (immunocytoma) in both the skin
      lesions and bone marrow, and IgM kappa paraprotein. Lesions cleared after
      chemotherapy.

PMID- 14639409
TI  - Buschke-Ollendorff syndrome: report of a case and interpretation of the clinical
      phenotype as a type 2 segmental manifestation of an autosomal dominant skin
      disease.
AB  - Buschke-Ollendorff syndrome is a rare, autosomal dominant disease consisting of
      osteopoikilosis and skin manifestations. A case is reported, and the literature
      is reviewed with special reference to the clinical distribution patterns of skin
      lesions. The 2 main types of skin manifestations in this entity are widely
      disseminated, symmetrically distributed papules and localized, asymmetrically
      distributed plaques. Both types of lesions have been observed within the same
      family or within the same person. This particular phenotype can be explained by
      type 2 segmental manifestation of an autosomal dominant cutaneous trait:
      Symmetrically distributed papules are a manifestation of the heterozygous state
      acquired by inheritance, and asymmetrically distributed plaques develop in areas
      that have undergone a somatic mutational event of the wild-type allele at an
      early developmental stage, the result being loss of heterozygosity.

PMID- 14639410
TI  - A new family with the rare genodermatosis keratosis punctata palmoplantaris
      Buschke-Fischer-Brauer.
AB  - We describe a new family with the rare genodermatosis keratosis punctata palmo
      plantaris Buschke-Fischer-Brauer (keratoma disseminatum). In all, 3 family
      members in 3 generations were affected, a pattern consistent with autosomal
      dominant inheritance. Clinical symptoms started in the third decade with
      disseminated, small, round, hyperkeratotic papules on the palms and soles.
      Punctate keratoses coalesced into hyperkeratotic plaques on pressure points.
      Identification of additional families is necessary to permit definitive genetic
      classification of this genodermatosis.

PMID- 14639412
TI  - Eosinophilic cellulitis as a cutaneous manifestation of idiopathic
      hypereosinophilic syndrome.
AB  - Three patients with eosinophilic cellulitis associated with sustained peripheral
      blood eosinophilia of unidentified cause are reported. They also presented with
      diversities of extracutaneous symptoms such as bronchospasm, sensory
      polyneuropathies, epigastralgia, and gangrenous eosinophilic enteritis. These
      cases suggest that eosinophilic cellulitis can develop as a cutaneous
      manifestation of idiopathic hypereosinophilic syndrome.

PMID- 14639411
TI  - Eosinophilic fasciitis and eosinophilic cellulitis in a patient with abnormal
      circulating clonal T cells: increased production of interleukin 5 and inhibition
      by interferon alfa.
AB  - Eosinophilic fasciitis (Shulman's syndrome) and eosinophilic cellulitis are part
      of a spectrum of diseases characterized by tissue and peripheral blood
      eosinophilia. Eosinophils are implicated directly in the lesional process that
      characterizes these conditions, because signs of eosinophil activation and
      degranulation are observed at the sites of tissue injury. The cause and
      pathogenesis of eosinophilic fasciitis and cellulitis are presently unclear.
      Herein, we report a patient manifesting rapidly progressive localized cutaneous
      induration of the arms and legs with eosinophilia, no signs of systemic
      sclerosis, and histopathologic features compatible with the diagnosis of
      eosinophilic fasciitis. Four years after the onset of eosinophilic fasciitis, the
      patient had recurrent episodes of eosinophilic cellulitis. Blood screening for
      clonal T-cell receptor gamma gene rearrangements revealed several amplified
      clonal populations of circulating T cells. Furthermore, in vitro analysis of
      cytokine production by the patient's peripheral blood mononuclear cells
      demonstrated strongly increased production of interleukin 5, the synthesis of
      which could be completely blocked by interferon (IFN)-alpha. The coexistence of
      eosinophilic fasciitis and cellulitis in a patient with an abnormal circulating T
      cell clone and increased IL-5 production are unique and might be responsible for
      the eosinophilia and eosinophil-mediated tissue injury. Although not assessed in
      vivo in this patient, our in vitro data provide a rationale for the use of IFN
      alpha in eosinophilic fasciitis and/or cellulitis.

PMID- 14639413
TI  - Syringolymphoid hyperplasia with alopecia: two case reports and review of the
      literature.
AB  - Syringolymphoid hyperplasia with alopecia is an uncommon, but histopathologically
      distinct, skin disorder that has been reported to occur with and possibly
      represent a syringotropic variant of cutaneous T-cell lymphoma. We report 2
      patients with syringolymphoid hyperplasia with alopecia. Both had CD4-positive
      infiltrates; 1 also demonstrated loss of CD7. One patient had evidence of T-cell
      clonality by gene rearrangement studies, but neither had histologic evidence of
      cutaneous T-cell lymphoma. Because the natural progression of syringolymphoid
      hyperplasia with alopecia remains to be fully explained, close follow-up of
      patients is advised.

PMID- 14639414
TI  - Lepromatous phlebitis of the external jugular vein.
AB  - Mycobacterium leprae (M leprae), the causative agent of Hansen's disease, is
      endemic in many areas of Asia, sub-Saharan Africa, South and Central America, the
      Pacific Islands, and the Philippines. The spectrum of clinical disease is
      dependent on the patient's cell-mediated immunity and might range from localized
      anesthetic patches or plaques to disseminated disease. If undiagnosed,
      progression with damage to the involved sensory and motor nerves might occur.
      Lepromatous vasculitis occurs most commonly in patients with severe disseminated
      disease. Vascular disease, as the initial presenting sign of tuberculoid leprosy,
      is, however, rare. We present one patient in whom the development of Hansen's
      disease was associated with involvement of the external jugular vein and was
      initially seen as external jugular vein fibrosis.

PMID- 14639415
TI  - Confluent and reticulated papillomatosis without papillomatosis.
AB  - Confluent and reticulated papillomatosis is a papulosquamous disorder that
      affects young individuals. There are several hypotheses regarding the cause,
      including genetic keratinization disorder, reaction to pityrosporum, and reaction
      to UV light. Multiple therapeutic agents have been used with variable success.
      The histologic findings include papillomatosis, hyperkeratosis, and minimal or no
      acanthosis. We present a patient with the clinical findings of confluent and
      reticulated papillomatosis who responded dramatically to minocycline, and in whom
      histologic examination did not reveal papillomatosis.

PMID- 14639416
TI  - Juvenile colloid milium associated with conjunctival and gingival involvement.
AB  - Juvenile colloid milium is an uncommon cutaneous disease characterized by
      translucent papules distributed on sun-exposed areas with early onset.
      Association of juvenile colloid milium with conjunctival and gingival deposits is
      uncommon and interesting. We report a case of juvenile colloid milium associated
      with conjunctival and gingivai deposits of an amyloid-like homogeneous
      eosinophilic material. It seems that all 3 of these in our patient may be
      different expressions of the same pathologic disease.

PMID- 14639417
TI  - Pseudoporphyria associated with hemodialysis treated with N-acetylcysteine.

PMID- 14639418
TI  - Successive linear, generalized, and oral lichen planus in a patient with chronic
      hepatitis C infection.

PMID- 14639419
TI  - Topical cidofovir for condylomata acuminata of the genitalia in a 3-year-old
      child.

PMID- 14639420
TI  - Alopecia areata after allogeneic bone marrow transplantation from an affected,
      human leukocyte antigen-matched sibling.

PMID- 14639421
TI  - Solar elastotic bands in a Japanese man.

PMID- 14639422
TI  - Treatment of facial lesion of cutaneous plasmacytosis with tacrolimus ointment.

PMID- 14639423
TI  - "Multifocal" circumscribed palmar hypokeratosis: malformation or not?

PMID- 14639424
TI  - Late complication of laser treatment.

PMID- 14639425
TI  - Helicobacter pylori CagA seropositivity is not strongly associated with lichen
      planus.

PMID- 14639426
TI  - Early diagnosis of fulminant group A streptococcal necrotizing fasciitis.

PMID- 14639427
TI  - Linear Darier's or Grover's disease?

PMID- 14639428
TI  - Accutane and pregnancy.

PMID- 14639429
TI  - Pregnancy rates associated with isotretinoin (Accutane) and the FDA.

PMID- 14639430
TI  - Leishmaniasis in Washington County, Texas.

PMID- 14639431
TI  - Promoting safe and effective sun protection strategies.

PMID- 14639432
TI  - Protecting against adverse effects of sun protection.

PMID- 14639433
TI  - Bacterial transfer and cross-contamination potential associated with paper-towel
      dispensing.
AB  - BACKGROUND: The role of hands in disease transmission is well established, and
      the importance of handwashing is recognized. However, the exits of paper-towel
      dispensers used in hand drying may be contaminated, and the functionality of
      handwashing equipment increasingly is being questioned. OBJECTIVES: We sought to
      study the transfer and cross-contamination potential between hands, towels, and
      dispenser exits if one or more is contaminated using bacteria representative of
      the skin's flora. MATERIALS AND METHOD: A generic wall-mounted paper-towel
      dispenser and a range of different paper towels were used. Volunteers with either
      clean or contaminated hands were asked to remove, using a range of protocols,
      towels from dispensers which themselves were either clean or contaminated.
      Previously clean surfaces were then microbiologically tested. RESULTS:
      Recoverable bacterial transfer rates from a contaminated hand to clean dispenser
      exits ranged from 0.01% to 0.64% depending on the bacteria used with an even
      higher transfer rate for clean towels. The reverse transfer (ie, from
      contaminated exits to clean hands) was between 12.4% and 13.1%. CONCLUSIONS: The
      results indicate that zig-zag transfer of bacteria between paper-towel dispensers
      and hands can take place if either one is contaminated. This potential should be
      considered in the design, construction, and use of paper-towel dispensers.

PMID- 14639434
TI  - Polyurethane II catheter as long-indwelling intravenous catheter in patients with
      cancer.
AB  - BACKGROUND: Silicone has been the standard material for indwelling devices to
      date. Polyurethane II exhibits properties that makes it suitable as a component
      of long-indwelling vascular access, with the added advantage of low cost.
      OBJECTIVE: To describe the experience of an intravenous therapy team with 206
      polyurethane II catheters used as long-indwelling vascular access in patients
      with cancer. MATERIALS AND METHODS: All polyurethane II single- and double-lumen
      catheters implanted between January 1, 1994, and March 15, 1995, were analyzed,
      including time of stay and type and rate of infectious and noninfectious
      complications. RESULTS: A total of 206 catheters were placed--164 single-lumen
      and 42 double-lumen catheters--in 190 patients; average stay was 101 days (range,
      1-445 days). The infection incidence rate was 0.66 per 1000 catheter-days for
      single-lumen catheters and 1.6 per 1000 catheter-days for double-lumen catheters.
      Noninfectious complications included 1 thrombosis (incidence rate, 0.06 per 1000
      catheter-days for single-lumen and none for double-lumen catheters), 5 catheter
      ruptures (2.4%), and 1 pneumothorax (0.48%). Twelve catheters (8.3%) were removed
      because of complications; only 1 was infectious. The remaining 17 infectious
      episodes (94.4%) were resolved without catheter removal. Our complication rate
      with single-lumen catheters in this series was similar to our previous experience
      with a nontunneled silicone catheter. CONCLUSIONS: Our findings indicate that
      polyurethane II catheters have proven useful and safe as long-indwelling vascular
      access in patients with cancer at our hospital at a considerably lower cost.

PMID- 14639435
TI  - Effect of comparative data feedback on intensive care unit infection rates in a
      Veterans Administration Hospital Network System.
AB  - BACKGROUND: Infection control surveillance is not performed with standardized
      methodology within the Veterans Affairs (VA) health system. The purposes of this
      study were (1) to provide network hospitals with a standardized intensive care
      unit (ICU) surveillance system developed by the Centers for Disease Control and
      Prevention (CDC); (2) to compare ICU infection rates in hospitals that receive
      comparative data with those that do not; and (3) to compare network device
      associated infection trends to national trends. METHODS: One VA Medical Center
      served as the central coordination site where surveillance data were analyzed
      with CDC's criteria and reported back to the sites. During 1999, the experimental
      group received risk-adjusted infection rates with national comparative data, and
      the control group received only risk-adjusted infection rates without comparative
      data. In 2000, hospitals in both groups received risk-adjusted infection rates
      accompanied by national data. RESULTS: In 1999, the device-associated infection
      rates were significantly higher in the control group compared with the
      experimental group. In the control group, the device-associated infection rates
      were significantly higher than the national comparative CDC rates; in the
      experimental group, the device-associated infection rates were not significantly
      different from the national comparative CDC rates. In 2000, the control group
      device-associated infection rates were not significantly different from the
      experimental group. The observed rates in both groups were not significantly
      different from the CDC rates. CONCLUSIONS: Study results suggest that infection
      rate outcomes may be reduced when national comparative data are provided. The
      study may serve as an infection control surveillance model for VA hospital
      networks.

PMID- 14639436
TI  - Effect of an infection control program using education and performance feedback
      on rates of intravascular device-associated bloodstream infections in intensive
      care units in Argentina.
AB  - OBJECTIVE: Our aim was to ascertain the effect of an infection control program,
      using education and performance feedback on intensive care units, for
      intravascular device (IVD)-associated bloodstream infection (BSI). METHODS:
      Within 4 level III, adult, intensive care units in Argentina, all admitted, adult
      patients with a central vascular catheter in place for at least 24 hours were
      included. This was a prospective before-and-after trial in which rates of IVD
      associated BSI determined during a period of active surveillance without
      education or performance feedback (phase 1) were compared after sequential
      implementation of an infection control program using education (phase 2) and
      performance feedback (phase 3). RESULTS: A total of 1219 IVD days were
      accumulated in phase 1; 586 during phase 2; and 4140 during phase 3. Compliance
      with central vascular catheter--site care improved significantly from baseline
      during the study period. Overall rates of IVD-associated BSI were lowered
      significantly from baseline after sequential implementation of education and
      performance feedback (11.10 vs 46.63 BSI/1000 IVD days; relative risk=0.25; 95%
      confidence interval=0.17-0.36; P<.0001). Rates of IVD-associated BSI decreased
      significantly after implementation of an educational program (phase 1 to phase 2)
      (relative risk 0.37; confidence interval 0.19-0.73; P=.0026) and further
      reductions were seen after implementation of a performance feedback program
      (phase 2 to phase 3), although the reduction did not reach statistical
      significance (9.9 vs 17.06 BSI/1000 IVD days; relative risk 0.58; confidence
      interval 0.29-1.18; P=.11). Additional analysis of the data using chi2 for trends
      demonstrated that sequential implementation of an education and performance
      feedback program resulted in a significant trend toward reduced rates of IVD
      associated BSI (P<.001). CONCLUSION: Implementation of an infection control
      program, using education and performance feedback, resulted in significant
      reductions in rates of IVD-associated BSI.

PMID- 14639438
TI  - Investigation of antimicrobial use pattern in the intensive treatment unit of a
      teaching hospital in western Nepal.
AB  - BACKGROUND: Inappropriate use of antimicrobials is of special importance in the
      intensive treatment unit because of the large number of drugs prescribed, the
      chance for drug errors, and the likelihood of development of drug resistance.
      METHODS: A total of 297 records of patients admitted to the intensive treatment
      unit of the Manipal teaching hospital, a tertiary care hospital in Pokhara,
      western Nepal, were studied to determine the prescribing frequency and
      rationality of use of antimicrobials. Patient outcome, duration of stay in the
      intensive treatment unit, and the age and sex distribution of the patients were
      also studied. RESULTS: Mean+/-SD drugs per patient was 3.4+/-1.8. About half
      (50.2%) of the patients received an antimicrobial; 84.6% of the antimicrobials
      were used without obtaining bacteriologic evidence of infection. The commonest
      organisms isolated on culture were Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Streptococcus pneumoniae, and Staphylococcus aureus. A total of 28.9% of the
      antimicrobials were prescribed for lower respiratory tract infections on the
      basis of the putative site of infection; 61.9% of the antimicrobials were
      prescribed by the parenteral route and mainly the older generation of
      antimicrobials were used. In 39 of the 149 patients prescribed an antimicrobial,
      the use was irrational. CONCLUSIONS: Prescriber education to improve prescribing
      patterns and regular auditing of antimicrobial prescriptions to prevent their
      inappropriate use and unnecessary cost to the patients are required. The high
      percentage of inappropriate use of antimicrobials raises concerns about the
      development and spread of drug resistance, which must be addressed.

PMID- 14639439
TI  - Influences on compliance with standard precautions among operating room nurses.
AB  - BACKGROUND: Occupational exposures of health care workers occur because of
      inconsistent compliance with standard precautions. The purpose of this study was
      to develop national estimates of compliance with standard precautions and
      occupational exposure reporting among operating room nurses (specifically, scrub
      nurses) in Australia and to assess variables that influence compliance. METHODS:
      A descriptive correlation design was used to investigate relationships between
      variables and compliance, using a theoretical framework, the Health Belief Model,
      to give meaning to the variables. Data collection was done through mail-out
      surveys to members of the Australian College of Operating Room Nurses. RESULTS:
      This article reports the results of compliance with the following 2 specific self
      protective behaviors: double-gloving and wearing adequate eye protection. Mean
      compliance rates were 55.6% with always double-gloving during surgical procedures
      and 92% with always wearing adequate eye protection. In addition, the variable
      that had the most influence on compliance was the perception of barriers to
      compliance, specifically, that adhering to standard precautions interfered with
      duties. CONCLUSION: These results have implications for the development of
      multifaceted perioperative infection control programs, including strategies for
      prevention, education, and policy development, to improve practices aimed at
      reducing occupational exposures among this high-risk group.

PMID- 14639440
TI  - A cluster of nosocomial Klebsiella pneumoniae bloodstream infections in a
      neonatal intensive care department: Identification of transmission and
      intervention.
AB  - OBJECTIVE: We sought to determine the cause and mode of transmission of a cluster
      of bloodstream infections as a result of Klebsiella pneumoniae. DESIGN AND
      SETTING: We conducted a prospective cohort study in a neonatal intensive care
      department from May 1999 to December 2000. METHODS: We performed surveillance of
      nosocomial infections, and clinical and environmental investigations. RESULTS:
      During an 8-week period, 5 cases of K pneumoniae bloodstream infections were
      observed, at least 3 of them belonging to the same genotype. Before the second
      case developed any symptoms of infection, the same strain had also been found in
      the patient environment. Intervention measures were, therefore, immediately
      introduced. Further cases, however, occurred in the following weeks. Even after
      further intervention activities and the end of the outbreak, the same strain was
      discovered in environmental samples from a stethoscope and a nurse's hand.
      CONCLUSIONS: Even where there is acute awareness of the problem and a generally
      high infection control level in a department, it is difficult to change behavior
      in such a way that further nosocomial infections can be totally excluded.

PMID- 14639441
TI  - Compliance with hepatitis B virus vaccination and risk of occupational exposure
      to blood and other body fluids in intensive care department personnel in Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) vaccine has been recommended to health care
      workers because of their frequent exposure to patient blood and other body fluid.
      METHODS: A cross-sectional study was done to determine the compliance with HBV
      vaccination, and the risk of occupational exposure to blood or other body fluids
      in intensive care unit (ICU) personnel (n=458) in Goiania, Brazil. RESULTS: The
      vast majority (95.5%) of ICU personnel reported HBV vaccination. Among those who
      did not, housekeepers were statistically associated with nonvaccination (P<.05).
      They had a 19.1-fold (95% confidence interval: 2.07-444.5) greater risk of
      nonvaccination compared with physicians. A total of 220 participants reported an
      incident with biologic fluids. Physician and nursing staff had a higher risk for
      occupational exposure to blood, other body fluids, or both when compared with
      housekeepers. CONCLUSIONS: This study showed a high frequency of HBV vaccination
      in ICU personnel in Brazil. Nevertheless, more efforts are necessary to increase
      compliance with vaccination in housekeepers. Physician and nursing staffs showed
      high risk of occupational exposure to blood, other body fluids, or both,
      ratifying the importance of continuous education programs concerning prevention
      of bloodborne pathogen transmission for all ICU personnel.

PMID- 14639442
TI  - Seroepidemiology study of Japanese encephalitis neutralizing antibodies in
      southern Taiwan: a comparative study between urban city and country townships.
AB  - BACKGROUND: Japanese encephalitis (JE) occurs all over Asia, especially in
      southeastern regions. The aim of this study was to evaluate the current JE
      vaccination regimen in Taiwan by assessing the neutralizing antibody among people
      of various age groups from different living environments. METHODS: From 1998 to
      1999, 2365 (1016 male, 1349 female) students and home-visit volunteers were
      recruited from an industrialized city (Kaohsiung), and 712 (290 male, 422 female)
      students and volunteers from hospital outpatient and physical check-up units were
      recruited from country townships (Pintung County) for this study. Participants
      were between 6 and 74 years old. Serum JE neutralizing antibody was measured by
      the plaque reduction neutralization test with a 50% reduction as seroconversion.
      Incidence cases from 1971 to 1999 were collected from an active surveillance
      system run by the Center for Disease Control in Taiwan. RESULTS: Seropositive
      prevalence peaked immediately after the second booster in first-grade students
      and declined as age increased. For those born before 1963, seropositive
      prevalence was significantly associated with age, sex, and living area. In the
      1990s, the incidences of confirmed JE in Kaohsiung and Pintung County were 0.11
      and 0.14 per 100,000 population, with only 2 and 1 patient age 10 years or
      younger, respectively. All but 2 patients had never been vaccinated. CONCLUSIONS:
      Seropositive prevalence decreased gradually after vaccination. A third booster
      (the fifth shot) before age 18 years may further enhance the antibody titers,
      especially if the odds of natural infections have significantly reduced. Follow
      up studies on the changes of antibody titers over time among immunized
      populations are warranted in Asian countries where natural infections become less
      common.

PMID- 14639443
TI  - Venturi atomizers as potential sources of patient cross-infection.
AB  - Venturi-principle atomizers, which rely on compressed air to aerosolize
      medications, are commonly used in clinical practice to apply topical anesthetics
      and vasoconstrictors to the mucous membranes of the nose and throat.
      Unfortunately, the mechanism by which these devices operate leads to aspiration
      of external contaminants back into the device at the end of the spray cycle. This
      "flaw" in design may make Venturi-principle atomizers unsafe for clinical
      practice because of the risk of patient cross-infection. This article reviews the
      mechanism of action of Venturi-principle atomizers, presents the scientific
      literature regarding their potential for cross-infection of patients, and
      discusses alternative device options.

PMID- 14639444
TI  - Adaptive robotic rehabilitation of locomotion: a clinical study in spinally
      injured individuals.
AB  - STUDY DESIGN: Clinical study on six spinal cord-injured subjects. The performance
      of two automatic gait-pattern adaptation algorithms for automated treadmill
      training rehabilitation of locomotion (called DJATA1 and DJATA2) was tested and
      compared in this study. OBJECTIVES: To test the performance of the two algorithms
      and to evaluate the corresponding patient satisfaction. We also wanted to
      evaluate the motivation of the patients to train with a fixed gait pattern versus
      training where they can influence and change the gait pattern (gait-pattern
      adaptation). SETTING: Spinal Cord Injury Center Paracare, Balgrist, Zurich,
      Switzerland. METHODS: The experimental data were collected during six blinded and
      randomized training trials (comprising three different conditions per algorithm)
      split into two training sessions per patient. During the experiments, we have
      recorded the time courses of the six parameters describing the adaptation.
      Additionally, a special patient questionnaire was developed that allowed us to
      collect data regarding the quality, perception, speed, and required effort of the
      adaptation, as well as patients' opinion that addressed their motivation. The
      achieved adaptation was evaluated based on the time course of adaptation
      parameters and based on the patient questionnaire. A statistical analysis was
      made in order to quantify the data and to compare the two algorithms. RESULTS:
      Significant adaptation of the gait pattern took place. The patients were in most
      cases able to change the gait pattern to a desired one and have always perceived
      the adaptation. No statistically significant differences were found between the
      performances of the two algorithms based on the evaluated data. However, DJATA2
      achieved better adaptation scores. All patients preferred treadmill training with
      gait-pattern adaptation. CONCLUSION: In the future, the patients would like to
      train with gait-pattern adaptation. Besides the subjective opinion indicating the
      choice of this training modality, gait-pattern adaptation also might lead to
      additional improvement of the rehabilitation of locomotion as it increases and
      promotes active training. SPONSORSHIP: The work was supported by The Swiss
      Commission for Technology and Innovation (Project No. 4005.1).

PMID- 14639445
TI  - Flawed trial of micturition in cervical spinal cord injury patients: guidelines
      for trial of voiding in men with tetraplegia.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: (1) To raise awareness of flawed
      trial of micturition (TOM) in male spinal cord injury (SCI) patients; and (2) to
      present guidelines for trial of voiding in male SCI patients. SETTING: Regional
      Spinal Injuries Centre, Southport, UK. METHODS: Trial of micturition in male SCI
      patients refers to discarding indwelling catheters and establishing them on
      balanced voiding with penile sheath drainage. We describe seven SCI patients,
      whose trial of micturition was flawed. RESULTS: Two patients (C-6 and C-4
      tetraplegia respectively) developed severe autonomic dysreflexia (headache,
      sweating, and increase in blood pressure) 2-3 h after removal of urethral
      catheter. A C-4 tetraplegic developed severe urinary infection after TOM. Four
      patients with tetraplegia started retaining increasing amounts of urine and
      developed urinary infections/autonomic dysreflexia/hydronephrosis 1-21 months
      after they were established on sheath drainage after TOM. CONCLUSION: During TOM,
      patients with cervical SCI could develop autonomic dysreflexia, urinary
      infection, or hold progressively increasing volumes of residual urine. TOM should
      be guided by videourodynamics. SCI patients need alpha-blockers, and
      anticholinergics if voiding pressures are >40-50 cm H(2)O. If high urethral
      resistances are found, sphincterotomy and/or bladder neck incision will help the
      patients to void by triggering. SCI patients, who had undergone successful TOM,
      require meticulous follow-up including urodynamics. Intermittent catheterisation
      without adequate medications based on cystometrogram may be hazardous, and may
      result in upper tract damage. Facilities for supplementary catheterisation (three
      to four times a day) should be available in the community if a patient is unable
      to maintain complete, low-pressure, emptying of bladder.

PMID- 14639446
TI  - Effect of training intensity on physical capacity, lipid profile and insulin
      sensitivity in early rehabilitation of spinal cord injured individuals.
AB  - STUDY DESIGN: Pre-post training intervention. OBJECTIVES: To evaluate the effect
      of training intensity on physical capacity, lipid profile and insulin sensitivity
      in early rehabilitation of spinal cord injured (SCI) patients, and to assess the
      correlation between peak aerobic capacity (VO(2Peak)) and insulin sensitivity.
      SETTING: Spinal Cord Rehabilitation Unit, Sunnaas Hospital, Nesoddtangen, Norway.
      METHOD: Six recently injured SCI individuals participated in the arm training
      intervention and were randomly admitted to a high-intensity (HI; 70-80% heart
      rate reserve (HRR)) and low-intensity (LI; 40-50% HRR) group. The 1 h interval
      training consisted of 3 min exercise bouts interspersed with 2 min of rest, three
      times a week for 8 weeks. In addition, a correlation coefficient was obtained
      between VO(2Peak) and insulin sensitivity in 11 SCI patients. RESULTS: The 8-week
      training program resulted in a significant increase in VO(2Peak) and maximal
      power output (PO(Max)) for the group as a whole (P<0.05). VO(2Peak) increased
      significantly more and total cholesterol/high-density lipoprotein cholesterol
      (TC/HDL-C) ratio and triglycerids decreased significantly more in the HI group
      than in the LI group (P=0.05). Training-induced changes in insulin sensitivity
      were significantly different between the groups (P=0.05), which was due to a
      nonsignificant decline in insulin sensitivity in the HI group and a
      nonsignificant improvement in the LI group. A significant positive correlation
      was found between VO(2peak) and insulin sensitivity (r=0.68, P=0.02). CONCLUSION:
      The interval arm training protocol as used in the present study enables recently
      injured SCI patients to do substantial work at a relatively high intensity.
      Results indicate that improvements in physical capacity and lipid profile were
      more pronounced in response to high-intensity training. The significant
      correlation between maximal oxygen consumption and insulin sensitivity indicates
      that, as in the able-bodied population, peak aerobic capacity is a predictive
      value with regard to insulin sensitivity in SCI. Future studies with larger
      groups assessing the role of exercise intensity on insulin sensitivity in SCI are
      suggested.

PMID- 14639447
TI  - Effect of stoma formation on bowel care and quality of life in patients with
      spinal cord injury.
AB  - INTRODUCTION: Bowel management is a significant source of concern for patients
      with spinal cord injury (SCI) and may significantly alter quality of life. The
      effect of colostomy formation on both quality of life and time taken for bowel
      care is well recorded. We report our experience of intestinal stoma formation in
      SCI patients. METHODS: Medical records from the spinal unit, operating theatres
      and stoma clinics were reviewed to identify SCI patients for whom a stoma had
      been formed. Patients were interviewed using a standard questionnaire. Average
      age at injury was 29 years (range 6-62 years). Mean time from injury to stoma
      formation was 17 years (range 0-36.25 years) and the mean period of poor bowel
      function prior to stoma was 8 years (range 1.5-25). RESULTS: The average time
      spent on bowel care per week decreased from 10.3 h (range 3.5-45) prior to stoma
      formation to 1.9 h (range 0.5-7.75) afterwards (P<0.0001, paired t-test). In all,
      18 patients felt that a stoma gave them greater independence and quality of life
      was described as much better by 25 patients. Complications occurred in 14
      patients - eight described leakage of mucus and occasionally blood and pus per
      rectum, three developed parastomal hernias and three developed bowel obstruction.
      CONCLUSION: Elective stoma formation is a safe and well-accepted treatment for
      the management of chronic gastrointestinal symptoms in patients with SCI.

PMID- 14639448
TI  - Domain-specific satisfaction in adults with pediatric-onset spinal cord injuries.
AB  - STUDY DESIGN: Interview using a structured questionnaire and standardized
      measures. OBJECTIVES: To determine domain-specific satisfaction levels in adults
      with pediatric-onset spinal cord injuries (SCI), to determine factors associated
      with these levels of satisfaction, and to determine the relationship of domain
      specific satisfaction to overall life satisfaction in this population. SETTING:
      US and Canada. METHODS: The participants were adults who sustained SCI at age 18
      years or younger and were 24 years of age or older at the time of interview and
      did not have significant head injury. In addition to providing information about
      themselves, including education level, employment, marital status, and community
      participation, they were asked to rate their level of satisfaction in seven
      domains: transportation in the community, educational achievement, employment
      opportunities, income, social/recreational opportunities, dating opportunities,
      and sexual experience. They also completed the satisfaction with life scale
      (SWLS), the Craig handicap assessment and reporting technique, the functional
      independence measure, and the short-form-12 perceived health scale. RESULTS: A
      total of 216 individuals were interviewed. The mean age at injury was 14 years
      and the mean age at interview was 29 years. From most satisfied to least
      satisfied, the domains were ranked in the following order: satisfaction with
      transportation in the community, educational achievement, social and recreational
      opportunities, sexual experiences, dating opportunities, job opportunities, and
      income. Age at interview, gender, and perceived health were identified in
      regression analyses as predictors of some of the domain-specific satisfactions,
      but the primary predictive factors were in the area of participation. Neither
      severity of neurologic impairment nor level of functional independence were
      predictors for any of the domains. Satisfaction in each of the domains was
      significantly associated with SWLS and satisfaction with dating, job
      opportunities, education, and income were identified as predictive factors in a
      regression analysis. CONCLUSIONS: Dating opportunities, job opportunities, and
      income are the three domains in which adults with pediatric-onset SCI are least
      satisfied and those domains have a significant impact on overall satisfaction.

PMID- 14639449
TI  - A specialist seating assessment clinic: changing pressure relief practice.
AB  - STUDY DESIGN: Description of a clinical service, evaluation of pressure relief
      practices. OBJECTIVES: To describe a specialist seating assessment clinic and a
      change in clinical practice arising from its work. SETTING: National Spinal
      Injuries Centre, Stoke Mandeville Hospital, UK. METHODS: Retrospective review of
      the ischial transcutaneous oxygen measurements of 50 newly injured and chronic
      spinal cord-injured (SCI) individuals seen in a specialist seating assessment
      clinic. Tissue oxygenation was measured in the sitting position (loaded) and
      during pressure relief (unloaded). RESULTS: Mean duration of pressure relief
      required to raise tissue oxygen to unloaded levels was 1 min 51 s (range 42 s-3
      min 30 s). CONCLUSION: These results confirmed the clinical perception that brief
      pressure lifts of 15-30 s are ineffective in raising transcutaneous oxygen
      tension (TcPO(2)) to the unloaded level for most individuals. Sustaining the
      traditional pressure relief by lifting up from the seat for the necessary
      extended duration is neither practical nor desirable for the majority of clients.
      It was found that alternative methods of pressure relief were more easily
      sustainable and very efficient.

PMID- 14639450
TI  - Holocord myelopathy with thoracic stenosis: case report and hypothesis.
AB  - STUDY DESIGN: Case report OBJECTIVE: To examine the resolution of holocord
      myelopathy based on the hypothesis of altered cerebrospinal fluid (CSF) dynamics.
      SETTING: Seoul National University Hospital, Seoul, Korea. METHOD: We describe a
      case of thoracic stenosis with holocord myelopathy, which suggests an alternative
      mechanism for the myelopathy. RESULT: Decompression of the thoracic stenosis
      resulted in the resolution of holocord myelopathy. CONCLUSION: Myelopathy may be
      caused by altered CSF dynamics and this type of myelopathy seems to be
      interstitial edema. Improvement of altered CSF flow dynamics could resolve this
      type of myelopathy.

PMID- 14639451
TI  - Subdural catheter migration may lead to baclofen pump dysfunction.
AB  - OBJECTIVES: To report an unusual cause of intrathecal drug delivery failure in
      baclofen pump device. STUDY DESIGN: A case report of an SCI patient treated with
      intrathecal baclofen, presenting a drug withdrawal. SETTING: Regional spinal cord
      injuries centre in Geneva (Switzerland). METHODS: We present a case of a 38-year
      old male with complete T9 spastic paraplegia for 15 years, treated with
      intrathecal baclofen for 11 years. He recently presented to our centre with a
      spastic hypertonic episode, associated with rhabdomyolysis. RESULTS: Standard
      investigations were unrevealing. However, a CT scan performed after injecting a
      radio-opaque solution by the side port of the pump, showed an unexpected catheter
      migration into the subdural space. Surgical revision reversed withdrawal
      symptoms. CONCLUSIONS: Subdural catheter migration must be considered in the
      differential diagnosis of intrathecal drug delivery system failures. We recommend
      the use of the CT scan after contrast injection, to detect the localization of
      the distal catheter tip and confirm the normal diffusion into the subarachnoid
      space.

PMID- 14639458
TI  - The politics of federal research.

PMID- 14639459
TI  - Domain organization of activation-induced cytidine deaminase.

PMID- 14639461
TI  - A birthday for B cells: Lymphopoiesis II, a scientific symposium honoring Max
      Cooper.

PMID- 14639462
TI  - TLR5 takes aim at bacterial propeller.

PMID- 14639463
TI  - Mast cells to the defense.

PMID- 14639464
TI  - Adjuvants and their signaling pathways: beyond TLRs.

PMID- 14639465
TI  - The NKT cell system: bridging innate and acquired immunity.

PMID- 14639467
TI  - Suppressors of cytokine signaling and immunity.
AB  - The suppressors of cytokine signaling (SOCS) and cytokine-inducible SH2 protein
      are key physiological regulators of the immune system. Principally, SOCS1 and
      SOCS3 regulate T cells as well as antigen-presenting cells, including macrophages
      and dendritic cells. Here we review the function of SOCS1 and SOCS3 in innate and
      adaptive immunity, with particular emphasis on the relationship between immune
      regulation and SOCS.

PMID- 14639469
TI  - Distinct expression of APO-1/Fas and caspase-8 in the human growth plate.
AB  - Chondrocytes in the growth plate undergo a characteristic sequel of
      differentiation processes, finally leading in their death by apoptosis. The
      mechanisms that mediate these remarkable biological phenomenon are still widely
      unknown. For this study, growth plates from five resected polydactylic infantile
      fingers were taken and immunostained for APO-1 and Caspase-8, two apoptosis
      mediating proteins. The expression of both proteins was examined in the resting
      zone, proliferating zone, and hypertrophic zone, representing the maturation
      stages of the growth plate. Positive cells for APO-1 and Caspase-8 were found in
      all zones of the physis with a significant increase from the resting to the
      hypertrophic zone (from 17.4% to 33.067% for APO-1 and from 13.17% to 28.22% for
      Caspase-8). Our findings suggest that both APO-1 and Caspase-8 are involved in
      chondrocyte development in the growth plate, predominantly near to the closure
      area.

PMID- 14639470
TI  - Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells
      derived from patients with ossification of the posterior longitudinal ligament.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is
      characterized by ectopic bone formation in the spinal ligaments. Mechanical
      stress, which acts on the posterior ligaments, is thought to be an important
      factor in the progression of OPLL. To clarify this mechanism, we investigated the
      effects of in vitro cyclic stretch (120% peak to peak, at 0.5 Hz) on cultured
      spinal ligament cells derived from OPLL (OPLL cells) and non-OPLL (non-OPLL
      cells) patients. The mRNA expressions of Cbfa1 (an osteoblast-specific
      transcription factor), type I collagen, alkaline phosphatase (ALP), osteocalcin
      and integrin beta1 (a mechanotransducer) were increased by cyclic stretch in OPLL
      cells, whereas no change was observed in non-OPLL cells. The effects of cyclic
      stretch on the spinal ligament tissues derived from OPLL and non-OPLL patients
      were also analyzed by immunohistochemistry using an antibody against Cbfa1. The
      expression of Cbfa1 was increased by cyclic stretch at the center of the spinal
      ligament tissues of OPLL patients, whereas no change was observed in the tissues
      of non-OPLL patients. Furthermore, U0126, a specific inhibitor of MAPK kinase
      (MEK), suppressed the stretch-induced mRNA expressions of Cbfa1, ALP and type I
      collagen in OPLL cells. These results suggest that in OPLL cells, mechanical
      stress is converted by integrin beta1 into intracellular signaling and that Cbfa1
      is activated through the MAP kinase pathway. Therefore, we propose that
      mechanical stress plays a key role in the progression of OPLL through an increase
      in Cbfa1 expression.

PMID- 14639471
TI  - A new paradigm to investigate the roles of head and eye movements in the
      coordination of whole-body movements.
AB  - Although previous studies have demonstrated the existence of coordinated eye and
      head movements during gaze shifts, none has studied the temporal and spatial
      characteristics of the various body segments during gaze transfers that require
      whole body movements. Without this information it is not possible to determine
      the extent of the interaction between the oculomotor control system and the motor
      control systems responsible for moving other body parts. Presented here is a
      detailed analysis of the timing and kinematic characteristics of participants' (
      N = 5) eye, head, upper body and feet during rotation of their body to align with
      light cues positioned at eccentric locations (45, 90, and 135 degrees, left and
      right of centre). For all rotation amplitudes there was a clear sequence of body
      segment orientation (eye, head, upper body and feet) consistent with previous
      studies of locomotor steering and significant correlations between the onset
      latency times of the eyes and all body segments. There were also significant
      correlations between temporally aligned kinematic profiles of the feet and the
      eye in space for all movement amplitudes. The extent of correlation was
      significantly lower for displacement profiles of the feet versus head and of the
      feet versus upper body. These findings demonstrate substantial eye-foot
      coordination during a novel whole-body rotation paradigm and provide evidence
      that the output of the motor systems responsible for moving the feet is heavily
      influenced by the motor systems responsible for generating and coordinating eye
      and head movements to peripheral targets.

PMID- 14639472
TI  - Stomatal conductance in a tropical xerophilous shrubland at a lava substratum.
AB  - Diurnal variation in leaf stomatal conductance (gs) of three xerophilous species
      (Buddleia cordata, Senecio praecox and Dodonaea viscosa) was measured over a 10
      month period during the dry and wet seasons in a shrubland that is developing in
      a lava substratum in Mexico. Averaged stomatal conductances were 147 and 60.2 (B.
      cordata), 145 and 24.8 (D. viscosa) and 142.8 and 14.1 mmol m(-2) s(-1) (S.
      praecox) during the wet and dry season respectively. Leaf water potential (Psi)
      varied in a range of -0.6 to -1.2 (S. praecox), -0.6 to -1.8 (B. cordata) and 
      0.9 to -3.4 MPa (D. viscosa) during the same measurement periods. Stomata were
      more sensitive to changes in irradiance, air temperature and leaf-air vapour
      pressure difference in the rainy season than the dry season. Although stomatal
      responses to Psi were difficult to distinguish in any season (dry or rainy), data
      for the entire period of measurement showed a positive correlation, stomata
      tending to open as Psi increased, but there is strong evidence of isohydric
      behaviour in S. praecox and B. cordata. A multiplicative model relating gs to
      environmental variables and to Psi accounted for 79%-83% of the variation of gs
      in three sites (pooled data); however, the performance of the model was poorer
      (60%-76%) for individual species from other sites not included in the pooled
      data.

PMID- 14639473
TI  - Evaporative cooling for Holstein dairy cows under grazing conditions.
AB  - Twenty-four grazing Holstein cows in mid and late lactation were randomly
      assigned to two treatment groups: control and cooled. The trial was performed at
      the Experimental Dairy Unit, Rafaela Agricultural Experimental Station (INTA),
      Argentina. The objective was to evaluate the effects of sprinkler and fan cooling
      before milkings on milk production and composition. The effects of the cooling
      system on rectal temperature and respiration rate were also evaluated. Cooled
      cows showed higher milk production (1.04 l cow(-1) day(-1)). The concentration
      and yield of milk fat and protein increased in response to cooling treatment. The
      cooling system also reduced rectal temperature and respiration rate. No effects
      were observed on body condition. It was concluded that evaporative cooling, which
      is efficient for housed animals, is also appropriate to improve yields and animal
      well-being under grazing systems. These results are impressive since the cooling
      system was utilized only before milkings, in a system where environmental control
      is very difficult to achieve. This trial was performed during a mild summer. The
      results would probably be magnified during hotter weather.

PMID- 14639475
TI  - Laparoscopic extraperitoneal approach to acutely incarcerated inguinal hernia.
AB  - BACKGROUND: Laparoscopic treatment of acutely incarcerated inguinal hernia is
      uncommon and still controversial. Those being performed almost all use the
      transabdominal (TAPP) approach. The authors here present their experience with
      totally extraperitoneal (TEP) repair of acutely incarcerated hernia. METHODS: A
      retrospective review was undertaken to evaluate the authors' experience with this
      procedure over a 4-year period. There were 16 cases, 5 of which were performed
      using a conventional anterior repair. These 5 cases were excluded from the
      review. The surgery for all of the remaining 11 acutely incarcerated hernias was
      started laparoscopically using the TEP approach. Eight of the cases were
      completed this way, whereas three were converted to the open procedure. In
      addition to standard TEP repair techniques, a releasing incision is required for
      acutely incarcerated direct, indirect, or femoral hernias. With a direct hernia,
      the opening of the defect is enlarged to allow safe dissection of its contents. A
      releasing incision is made at the anteromedial aspect of the defect to avoid
      injury to the epigastric or iliac vessels. With an indirect hernia, several
      additional steps are required. The epigastric vessels may be divided; an
      additional trocar may be placed laterally below the linea semicircularis to
      facilitate dissection of the sac and to assist with suturing of the divided sac;
      and the deep internal ring is divided anteriorly at the 12 o'clock position
      toward the external ring, facilitating dissection of the indirect sac. With a
      femoral hernia, a releasing incision is made by carefully incising the insertion
      of the iliopubic tract into Cooper's ligament at the medial portion of the
      femoral ring. RESULTS: The mean operative time was 50 min (range, 20-120 min),
      and the length of hospital stay was 5.4 days (range, 1-29 days). During a follow
      up period of 9 to 69 months, there was no recurrence, and only two complications.
      One of these complications was an infected mesh that occurred in a case involving
      cecal injury. It was treated with continuous irrigation and salvaged. The other
      complication was a midline wound infection after a small bowel resection for a
      strangulated obturator hernia. CONCLUSIONS: Familiarity with the anatomy involved
      leads to the conclusion that the laparoscopic approach, specifically the TEP
      procedure, can be used without hesitation even in cases of acutely incarcerated
      hernia.

PMID- 14639476
TI  - Natural transformation of the thermophilic cyanobacterium Thermosynechococcus
      elongatus BP-1: a simple and efficient method for gene transfer.
AB  - Proteins derived from the thermophilic cyanobacterium Thermosynechococcus
      elongatus BP-1, which performs plant-type oxygenic photosynthesis, are suitable
      for biochemical, biophysical and X-ray crystallographic studies. We found that T.
      elongatus displays natural transformation, and we established a simple and
      efficient protocol for transferring exogenous DNAs into the organism's genome. We
      obtained transformants directly on selective agar plates without having to
      amplify them prior to plating. We constructed several targeting vectors that
      enabled us to insert exogenous DNAs into specific sites without disrupting
      endogenous genes and operons. We also developed a new selectable marker gene for
      T. elongatus by optimizing the codons of the gene encoding a kanamycin
      nucleotidyltransferase derived from the thermophilic bacterium Bacillus
      stearothermophilus. This synthetic gene enabled us to select transformants as
      kanamycin-resistant colonies on agar plates at 52 degrees C. Optimization of the
      conditions for natural transformation resulted in a transformation efficiency of
      up to 1.7 x 10(3) transformants per microg of DNA. The exogenous DNAs were
      integrated stably into the targeted sites of the T. elongatus genome via
      homologous recombination by double crossovers.

PMID- 14639477
TI  - Neuroepithelial bodies in the lung of Melanophryniscus stelzneri stelzneri
      (Anura, Bufonidae).
AB  - Electron microscopy of the lungs of Melanophryniscus stelzneri stelzneri (Anura)
      revealed the presence of a complex pattern of corpuscular cells (CCs). The
      respiratory surface over the septa presents small areas where the CCs are grouped
      forming neuroepithelial bodies (NEBs). These corpuscular structures can also be
      localized in the inner layer of the lung wall. Although in both cases NEBs
      protrude slightly into the airway lumen, they are separated from the airway lumen
      and the basal connective tissue by thin apical and basal cytoplasmic processes of
      neighbouring pneumocytes. Ultrastructurally, the CCs possess a large nucleus,
      clear cytoplasm and vesicles of variable morphology and size, containing an
      electron dense material surrounded by a lucent space in some cases. The size of
      these dense-core vesicles (DCVs) ranged from 40 to 100 nm. The NEBs are
      associated with afferent and efferent terminal nerves. These types of nerve
      endings are located between the CCs and in the basal part of the NEBs. The
      location of the NEBs in strategic positions on the septa and in the wall of the
      lung, the presence of the DCVs in the basolateral region of the CCs, the
      occurrence of synaptic contacts between nerve endings and the CCs and the
      occurrence of capillaries close to the NEBs, suggest a receptosecretory function
      for NEBs in the lung of M.s. stelzneri.

PMID- 14639478
TI  - Voluntary activation and mechanical performance of human triceps surae muscle
      after exhaustive stretch-shortening cycle jumping exercise.
AB  - The purpose of this study was to examine neuromuscular factors that may
      contribute to post exercise force loss and subsequent recovery after exhaustive
      stretch-shortening cycle (SSC) exercise. Six subjects were fatigued on a sledge
      apparatus by 100 maximal rebound jumps followed by continuous submaximal jumping
      until complete exhaustion. Exercise-induced changes in neuromuscular performance
      were followed up to 7 days post exercise. The total number of jumps in the SSC
      exercise ranged from 336 to 1392. The SSC exercise induced a significant
      immediate plantarflexion torque decline of 29, 38 and 44% ( P<0.05) in maximal
      voluntary contraction and evoked maximal twitch and low-frequency (LF)
      stimulation, respectively. The higher the number of jumps in the SSC exercise the
      larger was the post exercise reduction in voluntary activation as well as in
      contractile force ( r=-0.94, P<0.01, in both). Furthermore, a higher number of
      jumps augmented a delayed force recovery and late decline in stretch reflex EMG
      response ( r=-0.94, P<0.01). Clear differences were found in central and
      peripheral adaptation to the exhaustive SSC exercise between the subjects. The
      magnitude of post exercise contractile and activation failure as well as the
      delayed recovery of neuromuscular performance may have been augmented in some
      subjects due to their high number of jumps in the exercise.

PMID- 14639479
TI  - The effects of resistance training on functional outcomes in patients with
      chronic obstructive pulmonary disease.
AB  - Aerobic exercise training is used for rehabilitation in patients with chronic
      obstructive pulmonary disease (COPD), although it has little effect on muscle
      weakness and atrophy. Resistance training may be a useful addition to aerobic
      programs for these patients. The purpose of the present study was to investigate
      the effects of resistance training in addition to aerobic training on functional
      outcomes in patients with COPD. Seventeen COPD patients enrolled in an aerobic
      based program that met twice a week were assigned to a 12-week control/aerobic
      [CON: n=8; 63 (8) years; mean (SD)] or a resistance/aerobic group [RES: n=9; 61
      (7) years]. RES trained an additional twice a week on 12 resistance machines,
      performing three sets of 8-12 repetitions at 32-64% of their one-repetition
      maximum (1-RM) lifts. RES (P<0.05) increased upper (36%) and lower (36%) body
      strength, as well as lean body mass (5%), while CON showed little to no change.
      The 12-min walk distance increased (P<0.05) in only the RES [676 (219) to 875
      (172) m]. Measurements of three of the eight tasks of activities of daily living
      improved in RES (P<0.05) compared to CON. This study demonstrated that
      progressive resistance training was well tolerated and improved functional
      outcomes in COPD patients that were currently involved in an aerobic training
      program.

PMID- 14639480
TI  - Ultrasonographic assessment of human skeletal muscle size.
AB  - The measurement of human muscle size is essential when assessing the effects of
      training, disuse and ageing. The considered 'gold standard' for cross-sectional
      area measurements of muscle size is magnetic resonance imaging (MRI). However,
      MRI is costly and often inaccessible. The aim of the present study was to test
      the reproducibility and validity of a more accessible alternative method using
      ultrasonography (ULT). We examined the cross-sectional areas in the vastus
      lateralis muscle of six individuals. Axial-plane ULT scans were taken at given
      levels along the entire muscle length. The ULT scanning was repeated on different
      days (reliability) and validated against MRI-based measurements. Mean intraclass
      correlation coefficients were 0.998 for the reliability of ULT and 0.999 for the
      validity of ULT against MRI. The coefficient of variation values for cross
      sectional area measurements assessed by six different experimenters were 2.1% and
      0.8% for images obtained with ULT and MRI, respectively. The ULT method is a
      valid and reliable alternative tool for assessing cross-sectional areas of large
      individual human muscles. The present findings justify the application of the ULT
      method for the detection of changes throughout large muscles in response to
      training, disuse or as a consequence of sarcopenia.

PMID- 14639482
TI  - A physiological counterpoint to mechanistic estimates of "internal power" during
      cycling at different pedal rates.
AB  - Reported values of "internal power" (IP) during cycling, generated by the muscles
      to overcome energy changes of moving body segments, are considerably different
      for various biomechanical models, reflecting the different criteria for
      estimation of IP. The present aim was to calculate IP from metabolic variables
      and to perform a physiological evaluation of five different kinematic models for
      calculating IP in cycling. Results showed that IP was statistically different
      between the kinematic models applied. IP based on metabolic variables (IP(met))
      was 15, 41, and 91 W at 61, 88, and 115 rpm, respectively, being remarkably close
      to the kinematic estimate of one model (IP(Willems-COM): 14, 43, and 95 W) and
      reasonably close to another kinematic estimate (IP(Winter): 8, 29, and 81 W). For
      all kinematic models there was no significant effect of performing 3-D versus 2-D
      analyses. IP increased significantly with pedal rate - leg movements accounting
      for the largest fraction. Further, external power (EP) affected IP significantly
      such that IP was larger at moderate than at low EP at the majority of the pedal
      rates applied but on average this difference was only 8%.

PMID- 14639483
TI  - Immediate mobilization gives good results in boxer's fractures with volar
      angulation up to 70 degrees: a prospective randomized trial comparing immediate
      mobilization with cast immobilization.
AB  - BACKGROUND: The management of the subcapital fracture of the fifth metacarpal
      bone, the boxer's fracture, is still a matter of debate. Besides the question of
      which rate of angulation is acceptable before a reduction becomes necessary,
      recommendations for further treatment of this fracture vary as well. Therefore,
      the aim of our study was to compare randomly and prospectively the results of an
      immobilization treatment for 3 weeks with cast with a functional treatment, all
      with accepted angulations up to 70 degrees. PATIENTS AND METHODS: Between June
      1997 and June 1998, 40 patients were randomly allocated either to treatment with
      an ulnar gutter plaster cast for a period of 3 weeks followed by mobilization, or
      a pressure bandage for 1 week and immediate mobilization within limits imposed by
      pain. All patients were monitored at the outpatient clinic 6 and 12 weeks after
      the fracture. Clinical outcome was measured by the range of motion (ROM) of the
      fifth metacarpal phalangeal (MCP) joint, and by interviewing the patients about
      their satisfaction, pain perception, return to work and hobby, and need for
      physiotherapy. RESULTS: A total of 35 patients with a mean age of 29 years (range
      15-84) completed the required follow-up program. The mean angulation of the
      fracture was 39 degrees (range 15-70 degrees ). Between the two groups, no
      statistical differences were scored with respect to ROM, satisfaction, pain
      perception, return to work and hobby, and need for physiotherapy. According to a
      sample size calculation (power 90%, alpha 0.05, to detect 5 degrees difference in
      ROM), 12 patients needed to be included in each group to reach significance.
      CONCLUSIONS: A pressure bandage for 1 week, followed by immediate mobilization,
      is a sufficient alternative treatment for a boxer's fracture, if it is not
      angulated greater than 70 degrees and not rotated. This treatment resulted in
      satisfied patients who perceived no more pain and had a good ROM of the fifth MCP
      joint. Reduction of angulated fractures of less than 70 degrees seems not of
      value, with respect to ROM of the fifth MCP joint.

PMID- 14639484
TI  - The development of diving bradycardia in bottlenose dolphins (Tursiops
      truncatus).
AB  - Bradycardia is an important component of the dive response, yet little is known
      about this response in immature marine mammals. To determine if diving
      bradycardia improves with age, cardiac patterns from trained immature and mature
      bottlenose dolphins ( Tursiops truncatus) were recorded during three conditions
      (stationary respiration, voluntary breath-hold, and shallow diving). Maximum
      (mean: 117+/-1 beats.min(-1)) and resting (mean: 101+/-5 beats.min(-1)) heart
      rate (HR) at the water surface were similar regardless of age. All dolphins
      lowered HR in response to apnea; mean steady state breath-hold HR was not
      correlated with age. However, the ability to reduce HR while diving improved with
      age. Minimum and mean steady state HR during diving were highest for calves. For
      example, 1.5-3.5-year-old calves had significantly higher mean steady state
      diving HR (51+/-1 beats.min(-1)) than 3.5-5.5-year-old juveniles (44+/-1
      beats.min(-1)). As a result, older dolphins demonstrated greater overall
      reductions in HR during diving. Longitudinal studies concur; the ability to
      reduce HR improved as individual calves matured. Thus, although newly weaned
      calves as young as 1.7 years exhibit elements of cardiac control, the capacity to
      reduce HR while diving improves with maturation up to 3.5 years postpartum.
      Limited ability for bradycardia may partially explain the short dive durations
      observed for immature marine mammals.

PMID- 14639481
TI  - Muscle strength, power and adaptations to resistance training in older people.
AB  - Muscle strength and, to a greater extent, power inexorably decline with ageing.
      Quantitative loss of muscle mass, referred to as "sarcopenia", is the most
      important factor underlying this phenomenon. However, qualitative changes of
      muscle fibres and tendons, such as selective atrophy of fast-twitch fibres and
      reduced tendon stiffness, and neural changes, such as lower activation of the
      agonist muscles and higher coactivation of the antagonist muscles, also account
      for the age-related decline in muscle function. The selective atrophy of fast
      twitch fibres has been ascribed to the progressive loss of motoneurons in the
      spinal cord with initial denervation of fast-twitch fibres, which is often
      accompanied by reinnervation of these fibres by axonal sprouting from adjacent
      slow-twitch motor units (MUs). In addition, single fibres of older muscles
      containing myosin heavy chains of both type I and II show lower tension and
      shortening velocity with respect to the fibres of young muscles. Changes in
      central activation capacity are still controversial. At the peripheral level, the
      rate of decline in parameters of the surface-electromyogram power spectrum and in
      the action-potential conduction velocity has been shown to be lower in older
      muscle. Therefore, the older muscle seems to be more resistant to isometric
      fatigue (fatigue-paradox), which can be ascribed to the selective atrophy of fast
      twitch fibres, slowing in the contractile properties and lower MU firing rates.
      Finally, specific training programmes can dramatically improve the muscle
      strength, power and functional abilities of older individuals, which will be
      examined in the second part of this review.

PMID- 14639485
TI  - Effects of season, food deprivation and re-feeding on leptin, ghrelin and growth
      hormone in arctic foxes (Alopex lagopus) on Svalbard, Norway.
AB  - The arctic fox (Alopex lagopus) is a medium-sized predator of the high Arctic
      experiencing extreme seasonal fluctuations in food availability, photoperiod and
      temperature. In this study, the plasma leptin, ghrelin and growth hormone (GH)
      concentrations of male arctic foxes were determined during a food deprivation
      period of 13 days and the subsequent recovery in November and May. Leptin,
      ghrelin and GH were present in arctic fox plasma in amounts comparable to other
      carnivores. The plasma leptin concentrations did not react to food deprivation
      unlike in humans and rodents. However, the leptin levels increased during re
      feeding as an indicator of increasing energy reserves. The relatively high
      ghrelin-leptin ratio, decrease in the plasma ghrelin concentration, an increase
      in the circulating GH concentrations and the observed negative correlation
      between plasma ghrelin and free fatty acid levels during fasting suggest that
      these hormones take part in the weight-regulation and energy metabolism of this
      species by increasing fat utilisation during food deprivation. The results
      strengthen the hypothesis that the actions of these weight-regulatory hormones
      are species-specific and depend on seasonality and the life history of the
      animals.

PMID- 14639486
TI  - Physiological and morphological characterization of honeybee olfactory neurons
      combining electrophysiology, calcium imaging and confocal microscopy.
AB  - The insect antennal lobe is the first brain structure to process olfactory
      information. Like the vertebrate olfactory bulb the antennal lobe is
      substructured in olfactory glomeruli. In insects, glomeruli can be
      morphologically identified, and have characteristic olfactory response profiles.
      Local neurons interconnect glomeruli, and output (projection) neurons project to
      higher-order brain centres. The relationship between their elaborate morphology
      and their physiology is not understood. We recorded electrophysiologically from
      antennal lobe neurons, and iontophoretically injected a calcium-sensitive dye. We
      then measured their spatio-temporal calcium responses to a variety of odours.
      Finally, we confocally reconstructed the neurons, and identified the innervated
      glomeruli. An increase or decrease in spiking frequency corresponded to an
      intracellular calcium increase or decrease in the cell. While intracellular
      recordings generally lasted between 10 and 30 min, calcium imaging was stable for
      up to 2 h, allowing a more detailed physiological analysis. The responses
      indicate that heterogeneous local neurons get input in the glomerulus in which
      they branch most strongly. In many cases, the physiological response properties
      of the cells corresponded to the known response profile of the innervated
      glomerulus. In other words, the large variety of response profiles generally
      found when comparing antennal lobe neurons is reduced to a more predictable
      response profile when the innervated glomerulus is known.

PMID- 14639487
TI  - Hydatid cysts of the adrenal gland: review of nine patients.
AB  - Adrenal cysts are very rare lesions, especially with parasitic origin. But with
      the wider application of ultrasonography (US) and computed tomography (CT) more
      adrenal cysts are detected incidentally. To gain more insight into this entity,
      the records of nine patients with hydatid cysts of adrenal gland seen at our
      department from January 1980 till January 2002 are reviewed. There were four men
      and five women, and their ages ranged from 15 to 80 years (median: 41 years). All
      of the patients had unilateral cysts. Seven cysts were located on the right and
      two on the left side. Five of the cysts were primary and four were secondary. In
      three patients the cysts were found incidentally. The most common presenting
      symptom was pain, which was present in six patients. An indirect hemagglutination
      (IHA) test was positive in six cases. In all patients, US and CT successfully
      imaged all cysts, but the definitive diagnosis was made by macroscopic and
      microscopic examination of the cyst's content. The patients were treated
      surgically. In all patients adrenal glands with the cystic masses were removed.
      The median follow-up period was 16 months (range: 6-64 months). No evidence of
      recurrence was found in any patient. It should not be forgotten that cystic
      masses of the upper abdomen might also originate from the adrenal gland. The
      etiology and nature of the cyst should be well researched, and appropriate
      treatment should be given as soon as possible. Surgical excision of the gland,
      including the cyst is the treatment of choice.

PMID- 14639488
TI  - Clinical value of parathyroid scintigraphy with technetium-99m
      methoxyisobutylisonitrile: discrepancies in clinical data and a systematic
      metaanalysis of the literature.
AB  - There is a considerable discrepancy in the literature concerning the sensitivity
      of parathyroid scintigraphy (PS) with 99mTc-MIBI. We therefore analyzed our own
      data and compared them to the literature in a metaanalysis. All patients who
      received 99mTc -MIBI scintigraphy and subsequent surgery in our department for
      the detection of enlarged parathyroid glands in primary (pHPT) or secondary
      (sHPT) hyperparathyroidism between 1991 and 1999 were included in our
      retrospective analysis. The results of surgery served as the gold standard. For a
      true positive result, the scintigraphy had to predict the exact location of
      parathyroid adenoma (PA) or parathyroid hyperplasia (PH). We then compared these
      data to the results of a nonstatistical systematic metaanalysis of the
      literature. Patients (178) underwent PS between 1991 and 1999; 139 were operated
      on and included in this study. Of these, 109 had pHPT and 30 had sHPT. The
      sensitivity and specificity of the PS were found to be 45%/94% for pHPT and
      39%/40% for sHPT. Fifty-two studies concerning PS were included in the
      metaanalysis. Sensitivities reported varied from 39% to >90%. Consideration of
      the different possible techniques used for PS could not explain these
      discrepancies. Our data show that the sensitivity of PS in clinical routine may
      be lower than expected from the literature. Our data are consistent with other
      studies and with partially unpublished clinical observations from other
      university hospitals. We believe that a well-designed and properly conducted
      prospective study is necessary to evaluate the reasons for the differences
      observed.

PMID- 14639489
TI  - Anastomotic healing in a small bowel transplantation model in the rat.
AB  - Anastomotic healing is impaired after intestinal surgery because of ischemia and
      reperfusion injury (IRI), which can result in intestinal leaks leading to
      increased mortality. The objective of this study was to determine the effects of
      transplant IRI and immune mechanisms on intestinal graft anastomotic healing.
      Orthotopic intestinal transplantations (OIT) were performed in rats. The
      experimental design consisted of six groups A-F (n=5/group): A, allogeneic OIT
      treated with tacrolimus (1 mg/kg/day); B, syngeneic OIT treated with tacrolimus;
      C, syngeneic OIT; D, allogeneic OIT; E, proximal and distal anastomoses performed
      in nontransplanted animals; F, same as in group E but treated with tacrolimus.
      Anastomotic bursting pressure (ABP), hydroxyproline content (HPC), and mucosal
      inflammatory infiltrate (MII) were determined at the anastomotic sites (proximal
      and distal) and compared between groups. ABP was significantly (p<0.001) reduced
      in OIT groups A, B, C, and D compared to control groups E and F at both the
      proximal and distal anastomotic sites. HPC was approximately 1 microg/mg of
      tissue in groups A, B, C, and D, and approximately 5 microg/mg of tissue in
      groups E and F. This demonstrates a significant (p<0.001) reduction in HPC after
      OIT. MII was significantly (p<0.001) increased in OIT groups when compared to
      nontransplanted control groups. MII was also significantly (p<0.05) increased in
      allogeneic OIT groups A and D compared to syngeneic OIT groups B and C.
      Generally, ABP and HPC were inversely proportional to MII in both nontransplanted
      control and OIT groups. Reduced anastomotic strength was demonstrated in both
      syngeneic and allogeneic OIT anastomotic sites irrespective of immunosuppressive
      therapy, and is probably related to IRI.

PMID- 14639490
TI  - Practice patterns in breast cancer surgery: Canadian perspective.
AB  - Breast cancer is a common disease, and the surgical management is continually
      evolving. The objective of this study was to describe the current breast cancer
      practice patterns among Canadian surgeons. All active General Surgeons (n=1172),
      as accredited by the Royal College of Physicians and Surgeons of Canada, were
      sent a 31-item questionnaire. Anonymous responses were collected and analyzed
      regarding surgeon demographics, practice, and perceptions regarding surgical care
      of breast cancer patients. Overall 640 active surgeons responded; of these, 519
      (81%) treated breast cancer and formed the study cohort. Practice settings
      included community (55%), community with university affiliation (28%), and
      academic (17%). The majority of surgeons (76%) stated that <25% of their practice
      was devoted to breast disease, and 42% performed < or =2 breast cancer
      operations/month. Immediate breast reconstruction (IBR) was used by 57% of
      surgeons. On multivariate analysis, higher surgeon volume of breast cancer cases
      (p=0.0008), fellowship training in Surgical Oncology (p=0.009), community
      population (p=0.001), and academic practice setting (p<0.0001) were independently
      associated with the use of IBR. Of the 640 surgeons who responded, 79% stated
      that breast cancer surgery should be performed by "most general surgeons." In
      Canada, most breast cancer surgery was performed by general surgeons who did not
      appear to have an interest, as defined by training or clinical volume, in breast
      cancer. Although variability regarding specific surgical issues was found among
      subgroups of surgeons, the majority of respondents felt that most general
      surgeons should treat breast cancer.

PMID- 14639491
TI  - Surgical intervention for obstructive jaundice due to biliary tumor thrombus in
      hepatocellular carcinoma.
AB  - This retrospective study in eight surgically treated patients with obstructive
      jaundice due to biliary tumor thrombus in a patient with hepatocellular carcinoma
      (HCC) was performed to evaluate the role of surgical intervention. All biliary
      tumor thrombi were confirmed preoperatively or intraoperatively. Only two
      manifested intraluminal biliary obstructions due to a primary tumor that had not
      been found preoperatively. The operative procedures included hepatectomy with
      removal of the biliary tumor thrombus (n=3), hepatectomy combined with
      extrahepatic bile duct resection (n=1), thrombectomy through a choledochotomy
      (n=3), and piggyback orthotopic liver transplantation (n=1). The 1- and 3-year
      survival rates were 62.5% and 37.5%, respectively. Two patients survived more
      than 5 years. Surgical intervention was effective in patients with obstructive
      jaundice due to a biliary tumor thrombus in an HCC. Thus surgery for a recurrence
      can prolong survival, and liver transplantation is a treatment worthy of further
      investigation.

PMID- 14639492
TI  - Gallbladder cancer in the twentieth century: single institution's experience.
AB  - The purpose of this study was to understand trends in the presentation,
      management, and outcome of patients of patients with gallbladder cancer treated
      over a period of 85 years at a single institution. We analyzed patients with
      gallbladder carcinoma treated at our institution between 1990 and 2000 (n=66).
      Data from this series were analyzed in the context of previously reported series
      from our institution (beginning in 1915) to understand trends in the
      presentation, management, and outcome of patients with gallbladder carcinoma. The
      mean age of patients has increased from 53.6 years (1915-1932) to 65.0 years
      (1990-2000). The gender (73% female) distribution of patients and most the common
      presenting symptoms (abdominal pain, weight loss, jaundice, nausea, abdominal
      mass) have not changed over the 85 years. More extensive surgery is being
      performed on patients with gallbladder carcinoma. The mean survival of patients
      with gallbladder cancer has increased from 3.6 months (1915-1932) to 10.0 months
      (1990-2000). The presentation of patients with gallbladder cancer has not changed
      over the 85 years. Most patients still present with advanced disease. The overall
      survival of patients with gallbladder cancer is poor, but it has improved since
      1915.

PMID- 14639493
TI  - Risk factors for mortality and morbidity after elective sigmoid resection for
      diverticulitis: prospective multicenter multivariate analysis of 582 patients.
AB  - The prevalence of diverticular disease of the colon is increasing in occidental
      countries. It would be useful to further decrease the mortality and morbidity
      after elective sigmoid resection (ESR) for diverticulitis. The aim of this study
      was to identify modifiable preoperative and intraoperative risk factors for
      mortality and morbidity after ESR for diverticulitis. A database of 2615 patients
      who underwent a colon or rectal resection with primary anastomosis between 1985
      to 1998 has been constructed from prospective randomized studies published by a
      French surgical group. Of those patients, 582 had undergone ESR for
      diverticulitis, and they constitute the population of the present study. A total
      of 46 potential preoperative and intraoperative risk factors for mortality and
      morbidity have been studied by univariate and multivariate analysis. The
      operative mortality for our series was 1.2%, and the overall morbidity was 24.9%.
      The multivariate analysis revealed two statistically significant independent risk
      factors of mortality: age >75 (odds-ratio=7.9; 95% confidence interval [CI 1.7
      36.6]; p=0.01) and obesity (odds-ratio=5.2; 95% CI [1.1-27.9]; p=0.04). The
      abdominal morbidity (AM) was 6.5% (38/582). The absence of antimicrobial
      prophylaxis administration with ceftriaxone was the only significant risk factor
      for AM in multivariate analysis (p=0.003; odds-ratio=2; 95% CI [1.1-4]). The
      extraabdominal morbidity (EAM) was 18.4% (107/582). Both chronic pulmonary
      disease (p=0.008; odds-ratio=2.9; 95% CI [1.4-6]; p=0.008) and cirrhosis (odds
      ratio=12; 95% CI [1.2-120]) proved to be significant risk factors for EAM. Weight
      control prior to surgery, routine administration of prophylactic preoperative
      antibiotics, and preoperative optimization of the respiratory status of patients
      with chronic pulmonary disease could decrease the postoperative mortality and
      morbidity associated with ESR for diverticulitis.

PMID- 14639494
TI  - Predictors of surgical outcome for complicated pneumonia in children: impact of
      bacterial virulence.
AB  - The charts of 110 children with community acquired bacterial pneumonia were
      reviewed. A subset of children who required surgical intervention for empyema or
      parapneumonic effusion was identified. Patients were divided into two treatment
      groups: antibiotics/tube thoracostomy alone (group 1) versus operative
      intervention (group 2). Overall, 33 (30%) of the children required surgical
      intervention for complications. Seventeen (15%, group 1) were successfully
      treated with antibiotics/tube thoracostomy alone, while 16 (15%) in group 2 were
      treatment crossovers, failing this initial therapy. Of group 2 children, 4 (25%)
      underwent thoracotomy and lobectomy, while 12 (75%) underwent video-assisted
      thoracoscopic surgery (VATS). Although group 2 children were younger than those
      in group 1 (4.4 +/- 3.6 versus 6.3 +/- 4.1 years, p<0.05) and had longer
      hospitalizations (20.1 +/- 10.1 versus 8.2 +/- 3.9 days, p<0.05), symptom
      duration, preoperative antibiotics, fibrinolytic use, and leukocytosis were
      similar (p>0.05). Group 1 children had 13 (76%) positive cultures, 92% with pan
      sensitivities, in contrast to group 2, which had 12 (75%) positive cultures, but
      only 33% were sensitive to first-line antibiotics (p<0.01). Group 2 patients were
      also more likely to have complex multi-loculated empyemas, pneumatoceles, or
      pulmonary necrosis identified on imaging studies (100% versus 24%, p<0.01). These
      data suggest that the natural history of pneumonia in children is heavily
      influenced by bacterial virulence. Tube thoracostomy and appropriate antibiotics
      remain effective for pan-sensitive, simple parapneumonic effusions and empyema.
      Complex parapneumonic effusions and empyema, however, which occur more frequently
      in the setting of first-line antibiotic resistance, often fail more conservative
      managements and may be best treated by earlier operative debridement.

PMID- 14639495
TI  - Living donor liver transplantation with special reference to ABO-incompatible
      grafts and small-for-size grafts.
AB  - Living donor liver transplantation (LDLT) has developed on the basis of increased
      safety of conventional liver surgery and the need for expanding donor sources,
      especially in children. Indications for LDLT were soon extended to adult patients
      in Japan, where cadaveric donation was limited. The right liver is now routinely
      transplanted to adults to avoid small-for-size graft syndrome, even though the
      right liver graft has the disadvantages of less remaining donor liver and the
      question of donor safety. Assessing the suitable size or quality of the graft, as
      well as of the remnant donor liver, is one of the most important problems in
      adult LDLT. Although several tactics have been proposed to manage the small-for
      size syndrome, their efficacy remains a question. We suggest that small-for-size
      syndrome is preventable by engaging in careful donor selection or using effective
      agents for hepatic microcirculatory disturbance control. Sometimes for LDLT only
      ABO-incompatible grafts are available from relatives, but they must be
      transplanted despite the expected poor outcome in adults and older children. To
      overcome the problems in this situation, we developed a novel protocol including
      intraportal infusion therapy with methylprednisolone, prostaglandin E1, and
      gabexate mesylate. Two adult patients undergoing ABO-incompatible LDLT have now
      survived 53 and 35 months after transplantation with good liver function.
      However, the other two patients suffered thrombotic microangiopathy
      postoperatively and died owing to cerebral hemorrhage or multiple organ failure,
      respectively. Further investigation is needed to improve the outcome of liver
      transplantation across the ABO blood group barrier.

PMID- 14639496
TI  - Cantlie's plane in major variations of the primary portal vein ramification at
      the porta hepatis: cutting experiment using cadaveric livers.
AB  - Major variations of the primary portal vein ramifications at the porta hepatis,
      such as trifurcation or an anterior sectorial trunk originating from the left
      portal vein (L+A pattern), seem to be relatively common morphologic features,
      with an incidence of 10% to 30%. However, it has not been clearly demonstrated
      whether the usual landmarks of Cantlie's line and the middle hepatic vein (MHV)
      are reliable indicators of the border between the right and left liver when these
      variations are present. We searched for any discrepancies between the actual
      left/right territorial border of the intrahepatic portal vein and the usual
      position of Cantlie's line or the MHV course using 30 fixed cadaveric livers with
      major variations including hilar trifurcation and the L+A pattern. In most livers
      (63.3%) the usual transection plane for left/right hepatectomy was occupied by
      Couinaud's segment VIII (S8), and the territory of the right portal vein extended
      to the left of Cantlie's plane. The MHV course did not correspond with the actual
      border between the right and left liver. Significant rightward shift of the MHV
      occurred in 76.9% of livers. The severity of the discrepancy seemed to depend on
      the distance between the origins of the anterior and posterior sectorial trunks
      along the main portal vein. In conclusion, variations of the primary portal
      ramifications alter the segmental configurations of the liver. Our results evoke
      doubt over the reliability of Cantlie's line and the MHV course as landmarks for
      major hepatectomy when such variations are present.

PMID- 14639497
TI  - A contribution to the Ecuadorian medical literature.

PMID- 14639503
TI  - Nonsense-codon-mediated decay in human hereditary complement C3 deficiency.
AB  - C3 occupies a central position in the complement pathway, mediating such diverse
      functions as convertase activity, opsonization and anaphylotoxin production. The
      deficiency of this protein is a rare autosomal recessive inherited disease,
      characterized by severe recurrent infections and immune complex disorders. We
      looked for molecular alterations that could explain the C3 deficiency present in
      a Brazilian boy of consanguineous parents who suffered from recurrent bacterial
      infections. Using reverse-transcriptase polymerase chain reaction to amplify C3
      mRNA from LPS-stimulated fibroblasts from the patient, we demonstrated that his
      C3 gene has no large structural aberrations. However, after sequencing the
      amplified and cloned products we found: (1). a L314P amino acid substitution;
      (2). silent mutations at codons P577, S798 and A1437; and finally, (3). an
      R848STer substitution that results in the production of a truncated protein.
      Densitometry studies revealed a lower C3 mRNA concentration in the patient's
      fibroblasts, suggesting an inherent instability of his C3 mRNA. Our results
      indicate the presence of a premature termination codon in the C3 gene that
      results in a lack of the protein in patient's serum, which correlates with the
      acceleration of C3 mRNA decay in the patient's fibroblasts. This mRNA instability
      is consistent with a nonsense-codon-mediated decay process that ensures the
      elimination of possible deleterious truncated proteins, which, in the case of
      constitutively expressed abundant proteins such as C3, may otherwise accumulate
      to significant levels, leading to toxicity.

PMID- 14639504
TI  - Wide-band tracheids are present in almost all species of Cactaceae.
AB  - Wide-band tracheids (WBTs) have been found in seedlings of most species of cacti
      that have fibrous wood in their adult bodies. Consequently, this cell type is now
      known to be present in almost all cacti. Earlier studies of adult plants revealed
      WBTs to be present only in cacti with globose or short, broad bodies, whereas all
      species with large columnar or long slender bodies had fibrous wood without WBTs.
      However, even these species produce WBTs during the first several months after
      germination. In species with fibrous wood in their adult bodies (species with
      large or slender bodies), seedlings undergo a phase transition in wood
      morphogenesis after a few months and stop producing the juvenile (WBT) wood and
      begin producing adult (fibrous) wood. If adult plants have an intermediate size,
      the phase transition is delayed and the plant produces WBT wood for several
      years. Species with globose bodies repress the phase transition completely and
      never switch to producing adult (fibrous) wood. Because WBTs are so widespread,
      they probably originated only once in Cactaceae, not multiple times as suggested
      earlier, or there may have been just a single origin in the
      Cactaceae/Portulacaceae clade.

PMID- 14639505
TI  - Measuring seating pressure, area, and asymmetry in persons with spinal cord
      injury.
AB  - The goal of this study was to measure characteristics of seat loading in manual
      wheelchair users with complete spinal cord injury (SCI). Pressure distribution on
      the seating area of 25 adult males with SCI and eight non-injured adult males was
      measured in a relaxed and an upright posture on a standardized hard surface.
      Subjects with SCI were also tested in their wheelchairs. Maximum pressure,
      contact area, area of the highest pressure, and three asymmetry indices were
      compared. Subjects with SCI have higher pressure distributed over a smaller area,
      have a much smaller contact area, and distribute the loading more asymmetrically
      than non-injured subjects. Upright posture only corrects for some loading
      problems, while the wheelchair corrects for more loading parameters. Routine
      clinical seat loading evaluation may lead to improved chair and cushion selection
      for patients with SCI and may even alert clinicians to patients at high risk for
      complications due to high or unbalanced loads.

PMID- 14639506
TI  - [Antisocial personality disorder evaluation with the prisoner's dilemma].
AB  - INTRODUCTION: The aim of this study is to evaluate cooperation problems in
      antisocial disorder with the prisoner's dilemma game, which, in mathematical game
      theory, is the paradigm of the <<non-zero>> games (mutual benefit from
      cooperation). METHODS: We have designed a computer version of the prisoner's
      dilemma (CDT-BD) that confronts the patient to a simulation of a reciprocal
      exchange situation. IPDE provided us a categorical and dimensional evaluation of
      26 controls from the community and 40 methadone patients. Only methadone patients
      obtained an antisocial diagnosis: 20 in the category of positive antisocial and
      10 in the probable antisocial category. Patients also fullfilled TCI and MACH-IV.
      RESULTS: CDT-BD is, according to the parent's opinion (mothers), a good
      correlation of real life behavior. CDT-BD shows a statistically significant
      poorer cooperation of antisocial patients this is catego rical evaluation (ve
      rsus in controls) and in dimensional evaluation true both for variables that
      measure non-cooperation due to the patient's initiative and those as a response
      to the computer provocation. This may be due to a tendency of antisocials to use
      interchange situations <<zero game>> strategies (you win what the other player
      loses) instead of non-zero games strategies. Non-cooperative responses are
      correlated to high scores on the MACH-IV scale (manipulative behavior and
      cognition) and revengeful in Treatment and Character Inventory (TCI).
      CONCLUSIONS: CDT-BD allows us to generate and test new hypotheses on the causes
      of the cooperation problems in antisocial patients using game theory paradigms.

PMID- 14639507
TI  - [Combination therapy with reboxetine for major depression patients who are
      partial or nonresponders to serotonin selective reuptake inhibitors].
AB  - INTRODUCTION: Recent studies have confirmed the usefulness of the therapeutical
      combination of two antidepressants from different pharmacological families in
      patients with single drug therapy resistant depression. METHODS: In this
      prospective 6 weeks open-labeled study, efficacy of combination strategy was
      evaluated. This included the addition of reboxetine to 34 outpatients with DSM-IV
      major depressive disorder, who had not responded previously, or who partially
      responded to conventional treatment in single drug therapy with serotonin
      selective reuptake inhibitors (SSRI). Data were analyzed on a intent-to-treat
      basis. RESULTS: Mean decrease in the 21 item Hamilton depression rating scale
      (HDRS) score was 49.4% (from 26.9 to 13.6; p<0.0001) and in the clinical global
      impressions scale (CGI) was 40.4% (from 4.6 to 2.7; p < 0.0001). At the end of
      the treatment, 47.1% of the patients we re considered in remission (HDRS < or =
      10), 55.9% evaluated as responders (HDRS < or = 50%) and 58.8% considered as
      having improvement (CGI<4). No serious side effects were observed during
      combination therapy, the most frequent being nervousness and the urinary
      hesitancy (5.9%). CONCLUSIONS: The results of this study suggest that addition of
      reboxetine to SSRI may be an effective and well-tolerated strategy in treatment
      resistant patients who have failed to adequately respond to single drug therapy
      with SSRI.

PMID- 14639508
TI  - [Assessment of needs for care of a schizophrenic patient sample from the Granada
      Sur Mental Health Care Area].
AB  - INTRODUCTION: The assessment of the needs for care for long term severe ill
      patients has been one of the areas of greatest interest since the community
      mental health system was established. OBJECTIVE: This study has aimed to describe
      the needs for care of a group of schizophrenic patients and to know if these
      needs are met by the public mental health network. METHODS: A cohort of 83
      schizophrenic patients was selected. The diagnosis was confirmed by the SCAN
      method. The Needs for Care Assessment instrument was used to assess the needs for
      care of the patients. RESULTS: The positive psychotic symptoms (98%) followed by
      slowness and underactivity (71%) are the most common clinical problems between
      the patients of the cohort. In regards to skills and abilities, the most common
      are those related with work (49%) and house keeping (domestic work, getting meal
      and domestic shopping, with 42, 41 and 41%, respectively). In regards to the
      state of the need, 81% of the clinical problems are covered while this is only
      40% in the social area. CONCLUSIONS: The clinical needs of the schizophrenic
      patients can be met by the mental health services established, oriented to the
      community care. However, attending social needs requires more rehabilitation,
      occupational and residential resources to be developed.

PMID- 14639510
TI  - [Review on the study of the theory of the mind in pervasive development disorders
      and schizophrenia].
AB  - The theory of mind (ToM) is a new concept which could be defined as the ability
      to make inferences on the intentions of others. This capacity has been used to
      explain childhood autism symptoms and recently an attempt has been made to refer
      it to schizophrenia. The authors aim to review the theory of mind concept, the
      different questions that could appear in neurocognitive sciences and the
      utilities that this hypothetical model has been given in the clinical practice.
      The authors also consider the contributions and restrictions that its use has in
      the field of pervasive developmental disorders and schizophrenia.

PMID- 14639509
TI  - [Quality of life, in depressed patients in Primary Health Care setting.
      Effectiveness and safety of venlafaxine extended release].
AB  - INTRODUCTION: The aim of this observational study was to evaluate effectiveness,
      tolerability and impact on quality of life of treatment with venlafaxine extended
      release at a dose of 75 to 150 mg/day, in depressed outpatients treated in
      Primary Health Care. METHODS: Observational, prospective, open-labeled study,
      carried out by 882 Primary Health Care physicians. Outpatients, between 18 and 70
      years of age with depressive symptomatology susceptible of treatment, with a
      Hamilton Depression Scale (HAM-D17) score 14 were included. Daily doses of 75 or
      150 mg of venlafaxine extended release were administered orally for 24 weeks.
      Antidepressant effectiveness was assessed using the HAM-D17 scale and quality of
      life with the Quality of Life in Depression Scale (QLDS), Spanish version.
      RESULTS: 4,747 patients were recruited, of which 4,320 were included in a
      intention to treat effectiveness analysis and 4,557 patients in a safety
      analysis. HAM-D17 and QLDS mean score significantly decreased from week 4 to the
      end of study. 86,2% of the patients were responders and 73.8% achieved remission
      of the symptoms. Likewise, 95% reported absence or mild somatic and psychic
      anxiety on the final visit. Tolerability was considered good or excellent for
      98.7% subjects. 191 patients (4.2%) reported adverse events. CONCLUSIONS:
      Venlafaxine extended release is a safe and effective drug that reduces depressive
      symptoms of Primary Health Care patients and improves their quality of life.

PMID- 14639511
TI  - [Utility of quetiapine in tardive dyskinesia].
AB  - INTRODUCTION: Neuroleptic induced tardive dyskinesia is a late appearing
      extrapyramidal disorder of involuntary, choreoatetoid movements. It may appear
      during chronic treatment with classical neuroleptics or a short time after its
      prolonged administration is interrupted. At present, there is no agreement on
      what would be the best way to treat dyskinesias. Clozapine is an alternative
      treatment to take into account, although the risk of agranulocytosis may be
      excessive to use it when there is a mild or moderate form of dyskinesia. Cases of
      improvement of dyskinesias both with olanzapine as well as with risperidone,
      although in a lower number, have been reported. Due to its receptor profile,
      quetiapine is the atypical antipsychotic that is most similar to clozapine, which
      leads us to consider it for the treatment of dyskinesias. METHODS: The first
      patient is a 66 year old woman with schizoaffective disorder of 16 years of
      evolution who has received many classical neuroleptics and who presents a picture
      or orolingual dyskinesias with a score of 28 on the AIMS scale. Treatment was
      substituted with Quetiapine until reaching a dose of 400 mg/day over 4 months,
      obtaining a decrease in the AIMS score up to 9. The second patient is a 60 year
      old woman diagnosed of bipolar disorder under treatment since 26 years of age
      with delusional jealousy ideation. Different atypical antipsychotics were used,
      all of them causing dyskinetic symptoms in the orolingual region, that
      disappeared with low doses of quetiapine, with good stabilization of her
      psychopathology. The third patient is a 33 old male diagnosed of paranoid
      schizophrenia when he was 18 years old. He was under maintenance treatment with
      haloperidol, biperiden and lorazepam, until 27 years of age, when the treatment
      was changed to risperidone, after presenting an orofacial tardive dyskinesia with
      masticatory type movements and lingual protrusion, with a 19 score on the AIMS
      scale. The change to quetiapine 600 mg/day reduced the score on the AIMS scale to
      3. DISCUSSION: Our experience, based on 3 cases, shows an early and lasting
      improvement of the tardive dyskinesia with quetiapine. This experience is
      reinforced by other investigators with similar cases. In all, we have 12 cases
      that support the efficacy of quetiapine in the treatment of tardive dyskinesias.

PMID- 14639512
TI  - [Psychiatric and neuropsychological legal assessment of traumatic brain damage
      and Law 30/95].
AB  - Medico-legal assessment of people who have suffered injuries in road traffic
      accidents must use Law 30/95 as a reference frame. Psychiatric and
      neuropsychological syndromes secondary to traumatic brain injury (TBI) are no
      exception and pose demanding challenges to physicians and psychologists. This
      paper analyzes descriptive and nosological difficulties face by psychiatrists and
      psychologists; their expert contribution includes translation of official
      diagnostic entities into categories published in the annex of Law 30/95. Our
      psychopathological repertoire was created in the 19th century and has hardly been
      revised since. The wide and varied types of neuropsychological impairments
      encountered in TBI have to be diagnosed within a very narrow range of DSM-IV and
      ICD-10 categories. The most common conflicts encountered in the medicolegal arena
      are revised: the differential diagnosis between dementia and combinations of
      organic personality disorder with cognitive impairment; differential diagnosis
      between spontaneous psychiatric illness (bipolar disorder, schizophrenia) and
      psychiatric syndromes secondary to brain injury (posttraumatic psychosis, organic
      bipolar disorder); differential diagnosis between concussional syndrome and
      organic personality disorder, cognitive impairment or organic affective disorder.
      Specific diagnostic guidelines are suggested for each of these clinical
      situations. Actas Esp Psiquiatr 2003;31(6):353-360 <FONT face="Courier New"
      size=2></FONT>

PMID- 14639513
TI  - [Response to electroconvulsive therapy in a case of erotomania].
AB  - Secondary erotomania has mainly been associated with functional psychosis
      (especially schizophrenia) and bipolar disorder. Traditionally, erotomania has
      been considered chronic and refractory to treatment, although cases of secondary
      erotomania with response to benzodiazepines, lithium, anticonvulsivants,
      antipsychotic drugs and electroconvulsive therapy have been described. In this
      paper, we present a clinical case of secondary erotomania related to paranoid
      schizophrenia with good response to electroconvulsive therapy and neuroleptics.
      Actas Esp Psiquiatr 2003;31(6):361-363

PMID- 14639514
TI  - [Neuroticism and its "miracles". A cross-cultural or an anachronist matter?].
AB  - Rare behaviors, extravagant beliefs and some sort of social isolation frequently
      put the clinicians on the trail of a psychotic disorder. If we add sudden onset
      and end, plus the existence of certain stressors that are thought to be
      precipitant, the initial hypothesis could be referred to with specific surnames:
      <<brief>> or <<acute and transient>>. The present case shows the need to weigh
      the adjectives applied to behavior and ideation (i.e. <<extravagant>> or
      <<weird>>) according to biographical and cultural references of <<normality>>. By
      means of this contextualization, what initially might have seemed to be a
      psychosis has a neurotic explanation or, using a rather anachronistic term,
      <<hysterical>> explanation in which the spectrum of beliefs plays a crucial
      pathoplastic roll.

PMID- 14639515
TI  - [A case of obsessive symptoms in Huntington's disease].
AB  - INTRODUCTION: Recently, some authors have postulated the existence of the so
      called <<obsessive spectrum>>. This would include disorders that have the common
      point of the presence of repetitive thoughts and actions, which may either have a
      <<compulsive>> or <<impulsive>> nature. Certain neurological disorders with
      repetitive movements have also been grouped within this spectrum, including some
      forms of epilepsy, Parkinson's disease, Sydenham's Chorea or Huntington's
      disease. There is evidence that physiopathological connections may exist between
      some of these conditions. METHODS: A case of a patient with Huntington's Chorea
      with obsessive signs and symptoms is presented. The patient is a 50 year old
      male, diagnosed of Huntington's Chorea who is being treated with 25 mg/day of
      clozapine and 10 mg/day of clorazepate. The patient refused to eat certain foods
      for <<fear of choking>>. He began to display other obsessive behaviors such as
      refusing to touch objects that might have been touched by others, and developed
      ritual checking methods. Treatment based on the administration of 40 mg/day of
      paroxetine was begun. With this treatment the compulsive symptoms have
      disappeared, as has the fear of choking. However, the choreic movements typical
      of his condition persist and the signs and symptoms associated with a process of
      dementia are becoming increasingly evident. CONCLUSIONS: It is concluded that the
      case described may well be a good example of obsessive spectrum, and that the
      underlying physio-pathology should be studied.

PMID- 14639516
TI  - [LV Annual Meeting of the Spanish Society of Neurology. Barcelona, Spain, 27-29
      November 2003. Abstracts].

PMID- 14639517
TI  - [Aspects of expertising which are jointly valid for German sociomedicine and
      statutory health care].
AB  - A project group of the Medical Advisory Board of the German Federal
      Rehabilitation Council (BAR) developed fundamental joint principles on experts'
      opinions according to the social law code no. IX (SGB IX). The principles aim at
      medical experts working in different social organisations and statutory health
      care insurances. It was intended to create a "sociomedical language" which should
      be used as jointly as possible by experts in rehabilitation and social medicine
      and which is based on the ICF (International Classification of Functioning,
      Disability and Health, WHO 2001). Its stringent application will increase the
      utility of medical expertise across different institutions. The authors recommend
      to evaluate whether this model could provide a tool in the communication and
      cooperation between different sectors of the health system. Part I describes the
      theoretical model, Part II its application to a virtual individual case history.

PMID- 14639518
TI  - [A theory-based study on psychosocial workload as an instrument of health
      promotion in a hospital].
AB  - Starting with theory-based assessment of workload as experienced by employees of
      a hospital we aim at facilitating measures of health promotion. Using the effort
      reward-imbalance model of psychosocial stress we look for differences in stress
      experience as related to objective work stressors and for associations of stress
      experience and subjective health. Two assessments (in 2000 and in 2002) showed
      pronounced differences in stress experience between professional groups and
      between points in time, which were both related to differences in objective
      workload. The expected associations between psychosocial stress and subjective
      health (assessed only in 2002) could be demonstrated consistently. As was shown
      by logistic regression analysis the risk for reduced subjective health was
      roughly 4 times higher for those in the upper tertile of the effort-reward
      imbalance index as compared to all others when controlling for age, sex and
      professional group. Sources of psychosocial workload could be identified which
      are modifiable by measures of health promotion.

PMID- 14639519
TI  - [Work satisfaction and absenteeism of nursing staff--comparative study of 1021
      nurse trainees and nurses].
AB  - PURPOSE: To analyse the high level of absenteeism among nursing trainees compared
      with nursing staff. Unlike previous studies, the present study focussed on work
      satisfaction and motivation. Specifically, combining satisfaction with
      absenteeism was a novel approach. METHOD: For assessing work satisfaction, a
      standardised form with 73 items in four areas was drafted and checked in a pre
      test (n = 150). 861 nurses and 159 trainees were interviewed. The absenteeism
      data given by the nursing staff were compared with the 'missing' records of the
      personnel department. RESULTS: In all areas it was found that, in particular,
      problems of organisation, personnel management and working atmosphere in the
      hospital were a burden on the employees. In detail, however, there were
      considerable differences between nurses and trainees in respect of appraisal.
      Work organisation: Although trainees rated work organisation aspects lower than
      nurses, direct relationship to work satisfaction was less pronounced. For the
      trainees, improvements are imperative in respect of active self-responsibility.
      Leadership/co-operation: Trainees rated supervisor behaviour and working
      atmosphere lower than their colleagues. There was a direct relation to
      satisfaction and absenteeism. Workload/stress: Although their responsibility was
      less, a larger proportion of the trainees felt stressed. This was directly
      related to work satisfaction and absenteeism. Fluctuation and turnover: 44% of
      the trainees would be prepared to work up to the age of retirement, but only 25%
      of the qualified staff. Nevertheless, three-quarters of the trainees and two
      thirds of the nurses would choose the same profession again. Hence, unfavourable
      local (internal) circumstances led to the discontent and not the profession as
      such. CONCLUSIONS: The extremely high absenteeism of nursing trainees calls for
      action on the part of school and hospital management. There is a need for better
      information and care before and during professional training, because workload
      will be higher at the end of the training. The study indicates possibilities of
      increasing work satisfaction and decreasing absenteeism of trainees.

PMID- 14639520
TI  - [Assessing social inequality in microcensus data and German national health
      examination survey].
AB  - To analyse the impact of social inequality on health and illness public health
      officials in Germany request for more data on socio-demographic indicators in
      official population statistics at Federal and State level. The aim of the study
      was to examine whether the national sample census Microcensus is suitable for
      scaling social inequality. For this purpose, coding instructions for calculating
      social strata index by Winkler were applied to databases of the Microcensus. The
      results were compared with the German Health Survey, because social data of this
      survey are already scaled according to the coding instruction for social strata
      index by Winkler. Data analyses were based on subgroups of North Rhine-Westphalia
      originated from national samples of Microcensus and German Health Survey. For
      index indicators "education" and "income" coding structure was transferred to
      databases of Microcensus without any problems. For index indicator "occupational
      status" occupational groups were less comparable. This refers to the
      classification of the occupational status of formerly employed people. However
      this limitation applies also to employees because the model for "occupational
      status" is assessed only on a four-year basis. From a methodical point of view it
      seems to be a problem that "household" has a different meaning in the index by
      Winkler and Microcensus and is only partly transferable to Microcensus databases.
      Additionally, identification of the main income earner of the household proved
      extremely difficult. Therefore, at the present conceptional stage of Microcensus
      it seems appropriate to classify occupational status as an individual criterion.

PMID- 14639521
TI  - [The influence exercised by the spouse or partner on diabetics--assessing the
      participation of spouses or lifelong associates in intensive inpatient training-
      an epidemiological study].
AB  - BACKGROUND: The purpose of this study was to analyse whether participation of
      spouses of patients with type-2 diabetes in a patient empowerment programme would
      result in improved metabolic control of diabetes. Values of glycated haemoglobin
      levels were used for the between-group comparisons. METHODS: This investigation
      was conducted as a cohort study in which 59 patients with type-2 diabetes
      participated. Follow-up data were checked after 12 months. We investigated the
      relative glycated haemoglobin levels, blood pressure, hypoglycaemia,
      hospitalisation, and weight at baseline and follow-up. The statistical analyses
      were performed using the software packages SPSS 10 and Epi Info 6. RESULTS: The
      studied group had an average duration of diabetes of 10.7 years (range 1.3-40.8
      years) and an age of 64 years (range 40-79 years). The group accompanied by their
      spouses did show a significant reduction of the average glycated haemoglobin
      level from 1.51 to 1.28 (p = 0.0001). By contrast, the reduction of 0.03 in the
      group without spouses was not significant (p = 0.558). Looking at the relative
      risk, it turned out that patients without spouses have a 2.3 times higher risk of
      developing a worse metabolic control after one year than patients with spouses.
      The logistical regression supported this trend. CONCLUSIONS: This study indicates
      that the participation of spouses of patients with type-2 diabetes in a patient
      empowerment programme contributes to an improvement in blood glucose control.

PMID- 14639522
TI  - [Evaluation of institution-overlapping treatment planning conferences in
      psychiatric care in the city of Wolfsburg].
AB  - Beginning with 1.9.2001 institution-overlapping treatment planning conferences
      are being carried out for mentally disturbed and handicapped persons, for whom a
      service based on paragraphs 39, 40 German Social Legislation is applied. In this
      study we report on the results of the evaluation. The survey contains analysis of
      files, interviews with clients, questioning of persons in charge as well as
      interviews with the experts who took part in the institution-overlapping
      treatment planning conferences. The results show that the majority of the
      clients, the persons in charge and the experts think that the treatment planning
      conferences are an important and necessary instrument. The cost-benefit ratio is
      mainly reasonable. Positive changes have been achieved for 80% of the clients.
      Within a short time the symptoms of two thirds of the clients have decreased.
      Above all a reduction of unemployment and with alcoholics a high rate of
      abstinence could be recorded. To increase acceptance and efficiency of the
      treatment planning conferences, this system must be developed further.

PMID- 14639523
TI  - [Glaucoma in practices of ophthalmologists].
AB  - The aim of this study is to describe the prevalence of glaucoma among patients of
      office-based ophthalmologists on the basis of accounting data. The data can be
      taken from the so-called Patient-physician-panel for morbidity analysis (ADT
      panel) that has been developed by the Central Research Institute of Ambulatory
      Health Care in Germany. In this panel, the treatment data of patients treated by
      selected office-based physicians in North Rhine and Brandenburg are included. In
      both regions, 30 ophthalmologists were involved in the survey. The two random
      samples that have been performed, include the treatment data of nearly 55,000
      patients from North-Rhine and of 58,000 patients from Brandenburg. The treatment
      prevalence of glaucoma with established diagnosis amounts to about 12% of the
      ophthalmologic patients in North Rhine and to about 13% in Brandenburg. If these
      figures are secondarily related to the total number of persons older than 39
      years who are insured via social health insurance funds in these regions, the
      rates are 2.8 or 2.9% respectively. The majority of patients suffering from
      glaucoma (including suspected cases and exclusion diagnoses) underwent tonometry
      and it can be assumed that most of the patients received medical treatment. With
      the help of the morbidity panel, glaucoma patients with established diagnosis can
      be distinguished from those patients for whom this diagnosis has only been
      excluded and from cases where the suspicion remained unconfirmed. The
      standardised treatment prevalence of glaucoma almost amounts to the same rate in
      both regions. Ophthalmologists should use the additional specifications of the
      ICD-10 code more often (especially for cases of suspicion and exclusion). This
      would also lead to a higher significance of the ICD-10 terms indicated.

PMID- 14639524
TI  - [Surveillance of viral hepatitis in Lower Saxony for investigating risk factors:
      results and experiences from a regional public health project 1999-2001].
AB  - In Lower Saxony, a regional public health project for an enlarged surveillance of
      viral hepatitis was carried out from 1999 to 2001. Five district public health
      authorities collected additional information on notified viral hepatitis cases in
      a standardised way, particularly regarding risk factors. In the survey, 270
      hepatitis (hep.) cases were investigated, among them hep. A 51 (18.9%), hep. B 87
      (32.2%) and hep. C 132 (48.9%). The proportion of chronic cases and healthy
      carriers was as follows: hep. A 0%, hep. B 47.1% and hep. C 79.5%. In
      approximately 50% of the cases of all three forms risk factors could be
      identified. The most frequent risk factors were in hep. A visits to foreign
      countries (29.4%), contacts to infected individuals (17.6%) and attendance at
      public institutions or care facilities (13.7%), in hep. B visits to foreign
      countries (24.1%), contacts to infected individuals (19.5%; sexual contacts
      16.1%) and medical treatments (19.5%) and in hep. C injecting drug use (31.1%)
      and medical treatments (18.2%; 9.8% blood transfusion in the past in combination
      with chronic hep. C). The results are in accordance with current data under the
      new infection protection law, where reporting of chronic cases was mostly
      abolished. In the survey, the well-known risk factors were confirmed, but some
      risks were reported more frequently than in other surveys, e. g. sexual behaviour
      for hep. B or injecting drugs for hep. C.

PMID- 14639525
TI  - Cockayne syndrome group B cellular and biochemical functions.
AB  - The devastating genetic disorder Cockayne syndrome (CS) arises from mutations in
      the CSA and CSB genes. CS is characterized by progressive multisystem
      degeneration and is classified as a segmental premature-aging syndrome. The CS
      complementation group B (CSB) protein is at the interface of transcription and
      DNA repair and is involved in transcription-coupled and global genome-DNA repair,
      as well as in general transcription. Recent structure-function studies indicate a
      process-dependent variation in the molecular mechanism employed by CSB and
      provide a starting ground for a description of the mechanisms and their
      interplay.

PMID- 14639526
TI  - Reciprocal crossovers and a positional preference for strand exchange in
      recombination events resulting in deletion or duplication of chromosome 17p11.2.
AB  - Smith-Magenis syndrome (SMS) is caused by an approximately 4-Mb heterozygous
      interstitial deletion on chromosome 17p11.2 in approximately 80%-90% of affected
      patients. Three large ( approximately 200 kb), complex, and highly homologous (
      approximately 98%) low-copy repeats (LCRs) are located inside or flanking the SMS
      common deletion. These repeats, also known as "SMS-REPs," are termed "distal,"
      "middle," and "proximal." The directly oriented distal and proximal copies act as
      substrates for nonallelic homologous recombination resulting in both the deletion
      associated with SMS and the reciprocal duplication: dup(17)(p11.2p11.2). Using
      restriction enzyme cis-morphism analyses and direct sequencing, we mapped the
      regions of strand exchange in 16 somatic-cell hybrids that harbor only the
      recombinant SMS-REP. Our studies showed that the sites of crossovers were
      distributed throughout the region of homology between the distal and proximal SMS
      REPs. However, despite approximately 170 kb of high homology, 50% of the
      recombinant junctions occurred in a 12.0-kb region within the KER gene clusters.
      DNA sequencing of this hotspot (positional preference for strand exchange) in
      seven recombinant SMS-REPs narrowed the crossovers to an approximately 8-kb
      interval. Four of them occurred in a 1,655-bp region rich in polymorphic
      nucleotides that could potentially reflect frequent gene conversion. For further
      evaluation of the strand exchange frequency in patients with SMS, novel junction
      fragments from the recombinant SMS-REPs were identified. As predicted by the
      reciprocal-recombination model, junction fragments were also identified from this
      hotspot region in patients with dup(17)(p11.2p11.2), documenting reciprocity of
      the positional preference for strand exchange. Several potential cis-acting
      recombination-promoting sequences were identified within the hotspot. It is
      interesting that we found 2.1-kb AT-rich inverted repeats flanking the proximal
      and middle KER gene clusters but not the distal one. The role of any or all of
      these in stimulating double-strand breaks around this positional recombination
      hotspot remains to be explored.

PMID- 14639527
TI  - A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup
      N.
AB  - Deletion of the entire AZFc locus on the human Y chromosome leads to male
      infertility. The functional roles of the individual gene families mapped to AZFc
      are, however, still poorly understood, since the analysis of the region is
      complicated by its repeated structure. We have therefore used single-nucleotide
      variants (SNVs) across approximately 3 Mb of the AZFc sequence to identify 17
      AZFc haplotypes and have examined them for deletion of individual AZFc gene
      copies. We found five individuals who lacked SNVs from a large segment of DNA
      containing the DAZ3/DAZ4 and BPY2.2/BPY2.3 gene doublets in distal AZFc. Southern
      blot analyses showed that the lack of these SNVs was due to deletion of the
      underlying DNA segment. Typing 118 binary Y markers showed that all five
      individuals belonged to Y haplogroup N, and 15 of 15 independently ascertained
      men in haplogroup N carried a similar deletion. Haplogroup N is known to be
      common and widespread in Europe and Asia, and there is no indication of reduced
      fertility in men with this Y chromosome. We therefore conclude that a common
      variant of the human Y chromosome lacks the DAZ3/DAZ4 and BPY2.2/BPY2.3 doublets
      in distal AZFc and thus that these genes cannot be required for male fertility;
      the gene content of the AZFc locus is likely to be genetically redundant.
      Furthermore, the observed deletions cannot be derived from the GenBank reference
      sequence by a single recombination event; an origin by homologous recombination
      from such a sequence organization must be preceded by an inversion event. These
      data confirm the expectation that the human Y chromosome sequence and gene
      complement may differ substantially between individuals and more variations are
      to be expected in different Y chromosomal haplogroups.

PMID- 14639528
TI  - Search for haplotype interactions that influence susceptibility to type 1
      diabetes, through use of unphased genotype data.
AB  - Type 1 diabetes is a T-cell-mediated chronic disease characterized by the
      autoimmune destruction of pancreatic insulin-producing beta cells and complete
      insulin deficiency. It is the result of a complex interrelation of genetic and
      environmental factors, most of which have yet to be identified. Simultaneous
      identification of these genetic factors, through use of unphased genotype data,
      has received increasing attention in the past few years. Several approaches have
      been described, such as the modified transmission/disequilibrium test procedure,
      the conditional extended transmission/disequilibrium test, and the stepwise
      logistic-regression procedure. These approaches are limited either by being
      restricted to family data or by ignoring so-called "haplotype interactions"
      between alleles. To overcome this limit, the present study provides a general
      method to identify, on the basis of unphased genotype data, the haplotype blocks
      that interact to define the risk for a complex disease. The principle
      underpinning the proposal is minimal entropy. The performance of our procedure is
      illustrated for both simulated and real data. In particular, for a set of Dutch
      type 1 diabetes data, our procedure suggests some novel evidence of the
      interactions between and within haplotype blocks that are across chromosomes 1,
      2, 3, 4, 5, 6, 7, 8, 11, 12, 15, 16, 17, 19, and 21. The results demonstrate
      that, by considering interactions between potential disease haplotype blocks, we
      may succeed in identifying disease-predisposing genetic variants that might
      otherwise have remained undetected.

PMID- 14639529
TI  - Capillary malformation-arteriovenous malformation, a new clinical and genetic
      disorder caused by RASA1 mutations.
AB  - Capillary malformation (CM), or "port-wine stain," is a common cutaneous vascular
      anomaly that initially appears as a red macular stain that darkens over years. CM
      also occurs in several combined vascular anomalies that exhibit hypertrophy, such
      as Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and Parkes Weber syndrome.
      Occasional familial segregation of CM suggests that there is genetic
      susceptibility, underscored by the identification of a large locus, CMC1, on
      chromosome 5q. We used genetic fine mapping with polymorphic markers to reduce
      the size of the CMC1 locus. A positional candidate gene, RASA1, encoding p120
      RasGAP, was screened for mutations in 17 families. Heterozygous inactivating
      RASA1 mutations were detected in six families manifesting atypical CMs that were
      multiple, small, round to oval in shape, and pinkish red in color. In addition to
      CM, either arteriovenous malformation, arteriovenous fistula, or Parkes Weber
      syndrome was documented in all the families with a mutation. We named this newly
      identified association caused by RASA1 mutations "CM-AVM," for capillary
      malformation-arteriovenous malformation. The phenotypic variability can be
      explained by the involvement of p120-RasGAP in signaling for various growth
      factor receptors that control proliferation, migration, and survival of several
      cell types, including vascular endothelial cells.

PMID- 14639530
TI  - Ebola hemorrhagic fever and septic shock.

PMID- 14639531
TI  - Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever:
      overexpression of tissue factor in primate monocytes/macrophages is a key event.
AB  - Disseminated intravascular coagulation is a prominent manifestation of Ebola
      virus (EBOV) infection. Here, we report that tissue factor (TF) plays an
      important role in triggering the hemorrhagic complications that characterize EBOV
      infections. Analysis of samples obtained from 25 macaques showed increased levels
      of TF associated with lymphoid macrophages, whereas analysis of peripheral blood
      cell RNA showed increased levels of TF transcripts by day 3. Plasma from macaques
      contained increased numbers of TF-expressing membrane microparticles.
      Dysregulation of the fibrinolytic system developed during the course of
      infection, including a rapid decrease in plasma levels of protein C. Infection of
      primary human monocytes/macrophages (PHMs) was used to further evaluate the role
      of TF in EBOV infections. Analysis of PHM RNA at 1-48 h showed increased TF
      transcripts, whereas levels of TF protein were dramatically increased by day 2.
      Thus, chemotherapeutic strategies aimed at controlling overexpression of TF may
      ameliorate the effects of EBOV hemorrhagic fever.

PMID- 14639532
TI  - Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without
      inducing the production of cytokines and full maturation.
AB  - Ebola virus (EBOV) and Marburg virus (MARV) cause rapidly progressive hemorrhagic
      fever with high mortality and may possess specialized mechanisms to evade immune
      destruction. We postulated that immune evasion could be due to the ability of
      EBOV and MARV to interfere with dendritic cells (DCs), which link innate and
      adaptive immune responses. We demonstrate that EBOV and MARV infected and
      replicated in primary human DCs without inducing cytokine secretion. Infected DC
      cultures supported exponential viral growth without releasing interferon (IFN)
      alpha and were impaired in IFN-alpha production if treated with double-stranded
      RNA. Moreover, EBOV and MARV impaired the ability of DCs to support T cell
      proliferation, and infected, immature DCs underwent an anomalous maturation.
      These findings may explain the profound virulence of EBOV and MARV--DCs are
      disabled, and an effective early host response is delayed by the necessary
      reliance on less-efficient secondary mechanisms.

PMID- 14639533
TI  - In vitro model for the study of the dissociation of increasing antigenemia and
      decreasing DNAemia and viremia during treatment of human cytomegalovirus
      infection with ganciclovir in transplant recipients.
AB  - The paradox phenomenon (i.e., the dissociation of increasing antigenemia and
      decreasing DNAemia and viremia) that occurs during treatment of human
      cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant
      recipients, was investigated by use of an in vitro model for the study of
      interactions between polymorphonuclear leukocytes and endothelial cells. The
      paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much
      lesser extent, in the presence of cidofovir, but not in the presence of
      foscarnet. The pathogenetic basis for such a paradox response was found, by use
      of drug concentrations in the range of 90%-99% of the inhibitory dose, to rely on
      the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e.,
      the simultaneous increase of antigenemia, viremia, and DNAemia), which is
      observed in clinical conditions associated with inefficacy of treatment due to
      drug-resistant strains, was also reproduced in vitro by use of drug-resistant
      HCMV strains. The conclusion for clinicians is that antiviral therapy must be
      changed only in the latter case.

PMID- 14639534
TI  - Quantification of Human T-lymphotropic virus type I (HTLV-I) provirus load in a
      rural West African population: no enhancement of human immunodeficiency virus
      type 2 pathogenesis, but HTLV-I provirus load relates to mortality.
AB  - Human T-lymphotropic virus type I (HTLV-I) provirus load was examined in a cohort
      of a population in Guinea-Bissau among whom human immunodeficiency virus (HIV)
      type 2 is endemic. Geometric mean of HIV-2 RNA load among HTLV-I-coinfected
      subjects was significantly lower than that in subjects infected with HIV-2 alone
      (212 vs. 724 copies/mL; P=.02). Adjusted for age, sex, and HIV status, the risk
      of death increased with HTLV-I provirus load; mortality hazard ratio was 1.59 for
      each log10 increase in HTLV-I provirus copies (P=.038). There is no enhancing
      effect of HTLV-I coinfection on HIV-2 disease, but high HTLV-I provirus loads may
      contribute to mortality.

PMID- 14639535
TI  - Prospective randomized trial of emtricitabine versus lamivudine short-term
      monotherapy in human immunodeficiency virus-infected patients.
AB  - We conducted a randomized, open-label, 10-day study that compared the
      antiretroviral activity of emtricitabine (FTC) 25, 100, and 200 mg once daily and
      lamivudine (3TC) 150 mg 2 times/day in 82 human immunodeficiency virus (HIV)
      infected patients with virus loads >5000 and <100,000 copies/mL who were naive
      for 3TC and abacavir. All FTC doses demonstrated potent antiretroviral activity.
      Significantly greater virus suppression was seen at the 200 mg/day dose of FTC
      than with the lower FTC doses and/or 3TC (P=.02, P=.04, and P=.04, respectively).
      At the 200 mg/day dose, FTC produced a 1.7-log10 mean reduction in virus load.
      Trough FTC levels at the 200 mg/day dose exceeded the in vitro 90% inhibitory
      concentration dose for FTC by 5-fold. The long plasma half-life and the superior
      antiviral activity versus 3TC of the 200 mg/day FTC dose confirmed the results of
      other studies and led to the selection of this dose for subsequent therapeutic
      trials.

PMID- 14639536
TI  - Improved outcomes with earlier initiation of highly active antiretroviral therapy
      among human immunodeficiency virus-infected patients who achieve durable
      virologic suppression: longer follow-up of an observational cohort study.
AB  - On the basis of studies with relatively short follow-up, treatment guidelines
      currently recommend that highly active antiretroviral therapy (HAART) be
      initiated in asymptomatic human immunodeficiency virus-infected patients when the
      CD4+ lymphocyte count is < or =200 cells/mm3. We assessed the development of a
      new opportunistic infection or death among 1173 patients initiating HAART.
      Durable virologic suppression was defined as having more undetectable (<400
      copies/mL) than detectable virus loads after the initiation of therapy. The
      median durations of therapy and follow-up were 29 and 36 months, respectively.
      Among patients who achieved durable virologic suppression, those with baseline
      CD4+ lymphocyte counts of <200 cells/mm3 tended to progress faster than those
      with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 (P=.09) and progressed
      faster than those with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.01).
      Among those with durable virologic suppression, there was no difference in
      disease progression between those with baseline CD4+ lymphocyte counts of 201-350
      cells/mm3 and those with durable virologic suppression with baseline CD4+
      lymphocyte counts of >350 cells/mm3 (P=.40). Initiating HAART with a CD4+
      lymphocyte count of <200 cells/mm3 was associated with a higher risk of disease
      progression, even with durable virologic suppression. HAART should be initiated
      at CD4+ lymphocyte counts of >200 cells/mm3.

PMID- 14639537
TI  - Prevalence and magnitude of human immunodeficiency virus (HIV) type 1-specific
      lymphocyte responses in breast milk from HIV-1-seropositive women.
AB  - Human immunodeficiency virus (HIV) type 1-specific cell-mediated immunity of
      breast milk may influence the likelihood of mother-to-child transmission of HIV-1
      via breast-feeding. In breast-milk specimens collected during the first month
      postpartum from HIV-1-seropositive women in Nairobi, HIV-1 gag-specific cellular
      responses were detected in 17 (47%) of 36, and env-specific cellular responses
      were present in 20 (40%) of 50. Peripheral blood lymphocyte responses against
      either gag or env were detected in 35 (66%) of the 53 subjects, 18 (51%) of whom
      had positive gag or env responses in their breast milk. In paired analyses of
      blood and breast milk, the mean magnitude of responses to env or gag stimulation
      in breast milk was significantly higher than that in blood and remained higher in
      breast milk after normalization of responses according to CD8+ lymphocyte count.
      These results suggest that CD8+ lymphocytes present in breast milk have the
      capacity to recognize HIV-1-infected cells and may be selectively transported to
      breast milk to reduce either viral replication or transmission in breast milk.

PMID- 14639538
TI  - Placental malaria and perinatal transmission of human immunodeficiency virus type
      1.
AB  - Prevalence of placental malaria in human immunodeficiency virus (HIV) type 1
      infected and -uninfected women and the effect of placental malaria on genital
      shedding and perinatal transmission of HIV-1 were examined. Genital samples for
      HIV-1 DNA RNA were collected during labor. Infants were tested for HIV-1 at 1 day
      and 6 weeks postpartum. Placental malaria was diagnosed by histopathological
      examination: 372 placentas of HIV-1-infected women and 277 of HIV-1-uninfected
      women were processed. A higher prevalence of placental malaria was seen in HIV-1
      infected women. No association was found between placental malaria and either
      maternal virus load, genital HIV-1 DNA, or HIV-1 RNA. Placental malaria did not
      correlate with in utero or peripartal transmission of HIV-1.

PMID- 14639539
TI  - Epidemiology of acute otitis media caused by Streptococcus pneumoniae before and
      after licensure of the 7-valent pneumococcal protein conjugate vaccine.
AB  - We studied, by pulsed-field gel electrophoresis, multilocus sequence typing and
      penicillin-binding protein 2b amplicon-restriction profiles, pneumococcal
      isolates recovered from children with acute otitis media during 1 January-31
      December 1999 and 2001. The proportion of nonvaccine serogroups increased from
      14.8% (13/88) to 36.5% (23/63) from 1999 to 2001 (P<.01). Among children who
      received at least 2 doses of the pneumococcal 7-valent protein conjugate (PNC7)
      vaccine, 46.7% (7/15) of the isolates had nonvaccine serogroups, compared with
      20.8% (26/125) of the isolates from children who did not receive the PNC7 vaccine
      (P=.05). Overall, the serogroups involved in capsular switching were 6-19-NT, 6
      14-35, 15-19, and the 19-Spanish 23F clone. In 1999 and 2001, 30.8% (4/13) and
      26.1% (6/23) of the nonvaccine serogroups were implicated in capsular switching,
      respectively. Continued surveillance will be of great importance as the
      distribution of the PNC7 vaccine increases.

PMID- 14639540
TI  - Atypical enteropathogenic Escherichia coli strains: phenotypic and genetic
      profiling reveals a strong association between enteroaggregative E. coli heat
      stable enterotoxin and diarrhea.
AB  - The virulence profiles of most atypical enteropathogenic Escherichia coli (EPEC)
      strains are unknown. A total of 118 typical and atypical strains of EPEC
      serotypes and non-EPEC serogroups isolated from children with or without acute
      diarrhea who were from different cities in Brazil were examined for virulence
      associated markers and adherence to HEp-2 cells, and also had random amplified
      polymorphic DNA (RAPD) analysis performed. Atypical strains were identical to
      typical strains with regard to the virulence factors encoded on the locus of
      enterocyte effacement (LEE). In contrast with typical EPEC strains, none of the
      atypical strains reacted with the bfpA probe, and half of the strains hybridized
      with the perA probe. Most atypical strains presented Tir sequences that
      correlated with enteropathogenic or enterohemorrhagic E. coli (98%), had LEE
      inserted in either selC or pheU (88%), and presented a typeable intimin (52%).
      Eighteen new serotypes were found in the EPEC strains. Atypical and typical EPEC
      strains belonged to different RAPD clusters. Most atypical strains showed a
      localized-like adherence pattern (61.5%). Of the non-LEE-encoded virulence
      factors, enteroaggregative E. coli heat-stable enterotoxin was noted most
      frequently (45%) and was significantly associated with diarrhea (P=.01). Thus,
      this virulence marker may be used as an additional tool for the diagnosis of
      truly atypical pathogenic strains.

PMID- 14639541
TI  - Secretion of the toxin ExoU is a marker for highly virulent Pseudomonas
      aeruginosa isolates obtained from patients with hospital-acquired pneumonia.
AB  - Overall, hospital-acquired pneumonia (HAP) caused by Pseudomonas aeruginosa is
      associated with high attributable mortality. Although the intrinsic virulence of
      P. aeruginosa undoubtedly contributes to this phenomenon, it is unclear whether
      all strains share this property or whether only a subpopulation of strains are
      capable of causing such severe disease. In this study, the virulence of 35 P.
      aeruginosa isolates obtained from patients with HAP by use of a cytolytic cell
      death assay, an apoptosis assay, and a mouse model of pneumonia. The virulence of
      individual isolates differed significantly from one to another in each of these
      assays. Increased virulence was associated with the secretion of ExoU, a toxin
      transported by the P. aeruginosa type III secretion system. Secretion of ExoS or
      ExoY, 2 other proteins transported by this system, was not consistently
      associated with increased virulence. Together, these findings suggest that
      secretion of ExoU is a marker for highly virulent strains of P. aeruginosa.

PMID- 14639542
TI  - Emergence of multidrug-resistant Salmonella enterica serotype Newport infections
      resistant to expanded-spectrum cephalosporins in the United States.
AB  - We describe a field investigation in New England that identified the emergence
      and epidemiology of new strains of multidrug-resistant Salmonella, Newport
      MDRAmpC, and summarize the Center for Disease Control and Prevention's
      surveillance data for these infections. In Massachusetts, the prevalence of
      Newport-MDRAmpC among Salmonella serotype Newport isolates obtained from humans
      increased from 0% (0/14) in 1998 to 53% (32/60) in 2001 (P<.001). In a
      retrospective case-control study, infection with Newport-MDRAmpC was domestically
      acquired and was associated with exposure to a dairy farm. Isolates from both
      humans and cattle had indistinguishable or closely related antibiograms and
      pulsed-field gel electrophoresis patterns. Nationally, the prevalence of
      ceftriaxone-resistant Salmonella increased from 0.5% in 1998 to 2.4% in 2001; 85%
      of the isolates in 2001 were Newport-MDRAmpC, and at least 27 states have
      isolated these strains from humans, cattle, or ground beef. These data document
      the widespread emergence of Newport-MDRAmpC strains in the United States and show
      that the 5-fold increase in the prevalence of Salmonella resistant to expanded
      spectrum cephalosporins, between 1998 and 2001, is primarily due to the emergence
      of Newport-MDRAmpC strains.

PMID- 14639543
TI  - Molecular epidemiology of Rhodococcus equi of intermediate virulence isolated
      from patients with and without acquired immune deficiency syndrome in Chiang Mai,
      Thailand.
AB  - We investigated the prevalence of virulent Rhodococcus equi in clinical isolates
      from 69 sporadic cases (60 men, 8 women, and 1 patient of unknown sex) in Chiang
      Mai, Thailand, between 1993 and 2001. Fifty were human immunodeficiency virus
      (HIV) positive, 3 were HIV negative, and HIV status was unknown for 16. Fifty-two
      (75%) of 69 isolates were strains of intermediate virulence that contained the
      virulence-associated 20-kDa antigen, and 17 isolates (25%) were avirulent. No
      virulent strains with the virulence-associated 15-17-kDa antigens were
      identified. R. equi was isolated from HIV-positive patients' houses and those of
      their neighbors: avirulent strains were widespread, but only 1 strain of
      intermediate virulence was isolated. R. equi strains of intermediate virulence
      were isolated from 4 (0.8%) of 500 submaxillary lymph nodes from apparently
      healthy pigs in Chiang Mai. The routes of R. equi acquisition should be
      investigated from the viewpoint of zoonosis and public health.

PMID- 14639544
TI  - Age-specific frequencies of antibodies to Escherichia coli verocytotoxins (Shiga
      toxins) 1 and 2 among urban and rural populations in southern Ontario.
AB  - In 173 urban residents and 232 rural dairy-farm residents (age range, 0-70 years)
      who were stratified for age, the frequency of antiverocytotoxin 2 antibodies (VT2
      Abs) (frequency in urban residents, 46%; frequency in rural residents, 65%) was
      significantly higher than that of antiverocytotoxin 1 antibodies (VT1 Abs)
      (frequency in urban residents, 12%; frequency in rural residents, 39%) (P< or
      =.001). The frequency of VT2 Abs (93%) was also significantly higher than that of
      VT1 Abs (50%) in 14 patients with hemolytic uremic syndrome (HUS) associated with
      verocytotoxin-producing Escherichia coli (VTEC) strains that expressed both
      toxins. In urban residents, the frequency of both antibodies tended to decrease
      between the first and the second decades of life, and it then increased until the
      fifth decade of life, before, in the case of VT2 Abs, decreasing again. This
      pattern, which inversely reflects the age-related incidence of HUS, is consistent
      with a role for antiverocytotoxin antibodies in protective immunity. In dairy
      farm residents, peak frequencies of antibodies to both toxins occurred during the
      first decade of life and remained elevated for 3 decades before decreasing, a
      pattern consistent with frequent exposure to bovine VTEC from an early age.

PMID- 14639545
TI  - Antibody to genome-derived neisserial antigen 2132, a Neisseria meningitidis
      candidate vaccine, confers protection against bacteremia in the absence of
      complement-mediated bactericidal activity.
AB  - Genome-derived neisserial antigen 2132 (GNA2132) is a novel vaccine candidate
      that was identified during the Neisseria meningitidis group B strain MC58 genome
      sequencing project. To assess the vaccine potential of GNA2132, we prepared
      antisera from mice immunized with recombinant GNA2132 (gene from strain
      NZ394/98). Anti-GNA2132 antibody bound to the surface of live bacteria from all 7
      capsular group B or C strains tested and elicited deposition of human C3b on the
      bacterial surface. However, with human or infant-rat complement, anti-GNA2132 had
      no detectable bactericidal activity (titer, <1:4) against the nominal strain,
      NZ394/98, and was bactericidal against only 2 of the other 6 strains tested.
      These differences between strains were unrelated to GNA2132 amino acid sequence
      or level of protein expression. Despite lack of bactericidal activity, anti
      GNA2132 antiserum passively protected infant rats against meningococcal
      bacteremia after challenge with all 5 resistant strains. GNA2132 is thus a
      promising vaccine candidate for prevention of disease caused by N. meningitidis.

PMID- 14639546
TI  - Helicobacter pylori induces antiapoptosis through buclear factor-kappaB
      activation.
AB  - Although Helicobacter pylori is classified as a definite carcinogen, the
      mechanism underlying gastric carcinogenesis is not yet clear. We previously have
      shown that H. pylori activates an antiapoptotic gene, the cellular inhibitor of
      apoptosis protein 2 (c-IAP2), the underlying mechanism of which was investigated
      in the present study. cDNA array and real-time PCR analyses indicated that H.
      pylori showed a stimulatory effect on the expression of c-IAP2. Isogenic mutant
      strains with impaired cag pathogenicity island (cagPAI) expression showed weaker
      induction. Analyses that used the in situ terminal deoxynucleotide transferase
      mediated dUTP nick end-labeling method indicated suppression of antiapoptosis by
      the antisense c-IAP2 oligonucleotide. Reporter assays with deletion and mutation
      constructs for the c-IAP2 promoter showed that nuclear factor-kappaB (NF-kappaB)
      binding sites are indispensable for transactivation. Super-repressor IkappaBalpha
      or NF-kappaB inhibitor reduced c-IAP2 transactivation by H. pylori, and exogenous
      expression of c-IAP2 inhibited apoptosis seen with H. pylori. In conclusion, H.
      pylori induces antiapoptosis through c-IAP2 transactivation following cagPAI
      dependent NF-kappaB activation. The interaction of these stimuli may play a role
      in gastric carcinogenesis.

PMID- 14639547
TI  - Cytokine mRNA expression in pneumococcal carriage, pneumonia, and sepsis in young
      mice.
AB  - We studied cytokine mRNA expression in Streptococcus pneumoniae carriage,
      pneumonia, and sepsis in 3-week-old, inbred C57BL/6 and BALB/c mice. Mice were
      inoculated intranasally with S. pneumoniae serotype 6B, 14, or 3. Survival,
      bacterial load in the nasopharynx (NP) and lungs, and mRNA levels of tumor
      necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin
      (IL)-10, and IL-12 in the spleen were analyzed. No baseline mRNA expression
      levels were found, except for TNF-alpha in C57BL/6 mice. Serotype 6B caused NP
      colonization only, a significant (P<.05) increase in the levels of TNF-alpha, and
      induction of TGF-beta and IL-12 mRNA. Serotype 14 caused NP and nonlethal lung
      colonization and induction of TGF-beta, IL-10, and IL-12. Serotype 3 caused NP
      colonization, pneumonia, 35% mortality, and no alteration in the mRNA expression
      of tested cytokines. Although activation of the immune system culminated in
      nonlethal disease, evasion of the immune system was associated with detrimental
      disease.

PMID- 14639548
TI  - Inability of a variant strain of Anaplasma phagocytophilum to infect mice.
AB  - Nymphal Ixodes scapularis ticks were collected from several sites in Rhode
      Island. Polymerase chain reaction and DNA sequencing were used to determine the
      presence and prevalence of Anaplasma phagocytophilum human agent (AP-ha) and a
      genetic variant not associated with human disease (AP-variant 1). The remaining
      ticks from each cohort were allowed to feed to repletion on either white-footed
      (Peromyscus leucopus) or DBA/2 (Mus musculus) mice. The engorged ticks and murine
      blood samples were evaluated for the presence of AP-ha and AP-variant 1. Although
      a high percentage of the infecting ticks harbored AP-variant 1, only AP-ha was
      amplified from the murine blood samples. Additional ticks were fed on
      immunocompromised SCID mice, and, again, only AP-ha was capable of establishing
      an infection, and only AP-ha could be detected by xenodiagnosis. These data
      suggest that AP-variant 1 cannot establish an infection in mice, and we propose
      that AP-variant 1 has an alternative natural reservoir, possibly white-tailed
      deer.

PMID- 14639549
TI  - Increasing incidence of hospitalization for bronchiolitis among Canadian
      children, 1980-2000.
AB  - We evaluated temporal trends in hospitalization for bronchiolitis found among
      Canadian children for 1980-2000. The rate of hospital admission increased in all
      provinces over the 2 decades for all age groups but was highest in those aged <6
      months. The mean length of stay decreased from 5.4 to 3.1 days (mean rate of
      decrease, 0.13 days/year; P<.0001). Because a concurrent increase in other
      respiratory diagnostic codes was not seen, it is unlikely that physician practice
      variation could explain this consistent trend over almost 2 decades, which may
      indicate a change in disease prevalence or severity.

PMID- 14639550
TI  - Th2 cytokines are associated with reduced worm burdens in a human intestinal
      helminth infection.
AB  - Although T helper 2 (Th2) cytokines are known to be critical in the generation of
      protective immunity against intestinal helminths in mouse models, it is unclear
      whether they are important in natural immunity against gut helminthiases in
      humans. Therefore, we investigated cytokine production in ex vivo whole-blood
      cultures in response to Ascaris lumbricoides antigen and mitogen in a cross
      section of a community where the parasite is hyperendemic. The intensity of A.
      lumbricoides infection was significantly reduced after age 11 years. Levels of
      cytokines associated with Th2 lymphocytes (interleukin [IL]-4, IL-9, IL-10, and
      IL-13) demonstrated an inverse relationship with intensity of A. lumbricoides
      infection only in individuals aged >11 years. Furthermore, the IL-9, IL-10, and
      IL-13 produced in response to parasite antigen were of primary importance in this
      relationship. These findings promote a role for Th2-mediated responses in the age
      dependent reduction of intestinal helminth infections in humans.

PMID- 14639551
TI  - Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection.
AB  - Plasmodia species, unlike humans, can utilize p-aminobenzoic acid (PABA) for the
      de novo generation of folate. Plasmodial enzymes for the synthesis of PABA via
      the shikimate pathway are being investigated as novel targets for malaria
      chemotherapy. We show that, despite the presence of biosynthetic machinery to
      synthesize PABA, Plasmodium yoelii, a rodent malaria species, requires exogenous
      dietary PABA for survival. Mice fed low-PABA diets do not die from lethal doses
      of P. yoelii. The initiation of a PABA-deficient diet after P. yoelii infection
      is established leads to the clearance of parasites and subsequent resistance to
      infection by P. yoelii. An intact immune system is not necessary for protection,
      given that mice with severe combined immunodeficiency were also protected by PABA
      deficient diet. Our studies suggest that the PABA content in the diet will affect
      the host clearance of malaria parasites and may affect the efficacy of treatments
      that target the shikimate pathway.

PMID- 14639552
TI  - Enzymatic degradation of prion protein in brain stem from infected cattle and
      sheep.
AB  - Prions-infectious agents involved in transmissible spongiform encephalopathies
      normally survive proteolytic and mild protein-destructive processes. Using
      bacterial keratinase produced by Bacillus licheniformis strain PWD-1, we tested
      conditions to accomplish the full degradation of prion protein (PrP) in brain
      stem tissue from animals with bovine spongiform encephalopathy and scrapie. The
      detection of PrPSc, the disease-associated isoform of PrP, in homogenates was
      done by Western blotting and various antibodies. The results indicated that only
      in the presence of detergents did heat pretreatment at >100 degrees C allow the
      extensive enzymatic breakdown of PrPSc to a state where it is immunochemically
      undetectable. Proteinase K and 2 other subtilisin proteases, but not trypsin and
      pepsin, were also effective. This enzymatic process could lead to the development
      of a method for the decontamination of medical and laboratory equipment. The
      ultimate effectiveness of this method of prion inactivation has to be tested in
      mouse bioassays.

PMID- 14639553
TI  - Living artificial heart valve alternatives: a review.
AB  - Conventional replacement therapies for heart valve disease are associated with
      significant drawbacks. The field of tissue engineering has emerged as an exciting
      alternative in the search for improved heart valve replacement structures. One of
      the principles behind this concept is the transplantation of living elements,
      embedded in a suitable scaffold material, to the diseased site where the
      structure becomes integrated with patients' tissue to restore natural function.
      Significant progress has been made in the last ten years in the development of a
      living artificial heart valve alternative (LAHVA), with the identification of
      potential replacement sources for valve cells, scaffolds to maintain the cells in
      a three-dimensional environment, and signals to promote tissue development. This
      review addresses the need for a tissue-engineered alternative to current
      prostheses and provides a detailed account of normal heart valve structure--the
      blueprint for LAHVA fabrication. The research efforts to create a viable LAHVA,
      including recent developments, are discussed. Particular attention is focused on
      the choice of cell source for LAHVA construction, the use of biodegradable
      natural and synthetic polymeric scaffolds as extracellular matrix derivatives,
      and exogenous stimulation of tissue growth. The critical challenges involved in
      LAHVA development and possible future areas of investigation are also discussed.

PMID- 14639554
TI  - The relationship between dorsal horn neurotransmitter content and allodynia in
      neuropathic rats treated with high-frequency transcutaneous electric nerve
      stimulation.
AB  - OBJECTIVE: To examine the relation between axon terminal neurotransmitter content
      in the dorsal horn and allodynia in neuropathic rats treated with high-frequency
      transcutaneous electric nerve stimulation (TENS). DESIGN: A completely randomized
      experimental design. Two groups of rats received a chronic constriction injury to
      the right sciatic nerve, and 2 groups did not. The rats were either treated or
      not treated with TENS. SETTING: Research laboratory. ANIMALS: Adult male Sprague
      Dawley rats (150-165g). INTERVENTIONS: TENS was delivered daily for 1 hour to the
      chronic constriction injury rats or to the uninjured rats through self-adhesive
      electrodes applied to the skin innervated by the right dorsal rami of lumbar
      spinal nerves 1 to 6. MAIN OUTCOME MEASURES: Thermal and mechanical pain
      thresholds were assessed bilaterally in the hind paws of all rats twice before
      the chronic constriction injury surgery (baseline) and then 12 days after the
      surgery. An analogous time frame of assessment was used for rats that did not
      have chronic constriction injury surgery. Thermal and mechanical allodynia were
      expressed as difference scores between the pain thresholds of the right and left
      hind paws. These values were normalized to differences that existed between the 2
      paws at baseline. The amino acid content of dorsal horn axon terminals was
      assessed bilaterally with high-pressure liquid chromatography, and values were
      normalized to wet weight. RESULTS: The mean level of thermal and mechanical
      allodynia did not differ between the TENS-treated and untreated rats with chronic
      constriction injury. However, there was a significant relation between the dorsal
      horn, axon terminal content of glutamate (adjusted R(2)=.45, P<.01) and glycine
      (adjusted R(2)=.51, P<.005) and the magnitude of mechanical allodynia present in
      TENS-treated chronic constriction injury rats, but not in any other group. As
      axon terminal glutamate and glycine decreased in the right dorsal horn and
      increased in the left, mechanical allodynia was reduced or absent. When this
      trend was reversed, mechanical allodynia was more severe. Daily TENS also reduced
      the mean axon terminal content of aspartate, glutamate, and glycine bilaterally
      in the chronic constriction injury rats from the level observed in untreated
      neuropathic rats (P<.05). CONCLUSION: The variability in responsiveness of
      mechanical allodynia to daily TENS treatment in neuropathic rats is related to
      the axon terminal content of glutamate and glycine in the dorsal horn. These
      findings may help explain a similar variability in humans when TENS is used to
      treat neuropathic pain.

PMID- 14639555
TI  - The predictive value of creatine phosphokinase and alkaline phosphatase in
      identification of heterotopic ossification in patients after spinal cord injury.
AB  - OBJECTIVE: To determine the predictive value of serum levels of creatine
      phosphokinase (CPK) and alkaline phosphatase (ALP) in identifying patients with
      spinal cord injury (SCI) who are at risk to develop heterotopic ossification (HO)
      at the hips. DESIGN: Prospective cohort study. SETTING: Tertiary-care level I
      trauma center. PARTICIPANTS: Consecutive sample of 18 adults with acute traumatic
      SCI. Patients were excluded if they had medical or surgical conditions that are
      known to cause elevated enzyme levels. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Conventional hip radiographs were taken approximately 3 weeks
      after injury and again from between 3 to 6 months after injury. Serum ALP and CPK
      were measured approximately 3 weeks after SCI. Patients were later separated into
      2 groups: group 1 was comprised of those who developed HO and group 2 was
      comprised of those who did not. RESULTS: The initial radiographs showed no
      evidence of HO in either group. The radiographs taken at 3 to 6 months showed HO
      in 7 of 18 patients. The levels of CPK at the initial evaluation were
      significantly higher (R=.947, P<.0024) in group 1 than in group 2 and correlated
      with the severity of HO. There was no correlation between serum ALP levels and
      subsequent development of HO between the 2 groups (P=.07). CONCLUSION: Elevated
      serum levels of CPK have value in predicting the HO.

PMID- 14639556
TI  - Effects of arthritis exercise programs on functional fitness and perceived
      activities of daily living measures in older adults with arthritis.
AB  - OBJECTIVE: To ascertain the effectiveness of the National Arthritis Foundation
      (NAF) aquatic and on-land exercise programs on functional fitness and perceived
      ability to perform activities of daily living (ADL) measures in older adults with
      arthritis. DESIGN: The effects of aquatic and on-land exercise intervention
      programs were analyzed by repeated-measures analysis of variance by using a
      planned comparison approach with an independent 3 x 2 (group by test) design.
      omega(2) analyses were used to ascertain the relative treatment magnitude of each
      dependent variable. SETTING: Testing in an indoor track facility; exercise
      programs conducted in community settings. PARTICIPANTS: A volunteer sample of 30
      men and women with arthritis (osteoarthritis, n=22; rheumatoid arthritis, n=8),
      randomly assigned into either an aquatic exercise (n=10), on-land exercise
      (n=10), or control group (n=10). INTERVENTION: Eight-week on-land and aquatic
      exercise program. MAIN OUTCOME MEASURES: Functional fitness, ADLs, and hand-held
      dynamometry measures assessed on a 1-day pretest and posttest session, before and
      after an 8-week exercise program. RESULTS: Aquatic and on-land exercise subjects
      showed significant improvements on 9 of 12 functional fitness, 3 of 4 ADLs, and 7
      of 8 hand-held isometric strength tests after their respective exercise programs.
      No significant changes were found in any of these measures for the control group.
      CONCLUSION: Both NAF exercise programs appear to be effective in improving
      functional physical fitness and perceived ability to perform ADL measures in
      older adults with arthritis.

PMID- 14639557
TI  - Decreased peak arteriovenous oxygen difference during treadmill exercise testing
      in individuals infected with the human immunodeficiency virus.
AB  - OBJECTIVE: To determine if arteriovenous oxygen difference was lower in
      asymptomatic individuals with human immunodeficiency virus (HIV) infection than
      in sedentary but otherwise healthy controls. DESIGN: Quasi-experimental cross
      sectional. SETTING: Clinical exercise laboratory. PARTICIPANTS: Fifteen subjects
      (10 men, 5 women) with HIV and 15 healthy gender- and activity level-matched
      controls (total N=30). INTERVENTION: Participants performed an incremental
      maximal exercise treadmill test to exhaustion. Electrocardiogram, metabolic, and
      noninvasive cardiac output measurements were evaluated at rest and throughout the
      tests. Data were analyzed by using analysis of covariance. MAIN OUTCOME MEASURES:
      Peak oxygen consumption (Vo(2)), cardiac output, stroke volume, and arteriovenous
      oxygen difference. The arteriovenous oxygen difference was determined indirectly
      using the Fick equation. RESULTS: Peak VO(2) was significantly lower (P<.0005) in
      participants with HIV (24.6+/-1.2mL.kg(-1).min(-1)) compared with controls
      (32.0+/-1.2mL.kg(-1).min(-1)). There were no significant intergroup differences
      in cardiac output or stroke volume at peak exercise. Peak arteriovenous oxygen
      difference was significantly lower (P<.04) in those infected with HIV (10.8+/-0.5
      volume %) than in controls (12.4+/-0.5 volume %). CONCLUSION: The observed
      deficit in aerobic capacity in the participants with HIV appeared to be the
      result of a peripheral tissue oxygen extraction or utilization limitation. In
      addition to deconditioning, potential mechanisms for this significant attenuation
      may include HIV infection and inflammation, highly active antiretroviral therapy
      medication regimens, or a combination of these factors.

PMID- 14639558
TI  - Chronotropic incompetence in persons with down syndrome.
AB  - OBJECTIVE: To investigate the chronotropic response to exercise through peak
      heart rate and the Chronotropic Response Index (CRI) in participants with Down
      syndrome (DS) and in nondisabled control participants. DESIGN: Comparative study
      describing the acute exercise heart rate response. SETTING: University sports
      medicine facility. PARTICIPANTS: Twenty participants with DS (mean age +/-
      standard deviation, 24.2+/-3.5y) and 20 control participants without disabilities
      (age, 21.2+/-2.8y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Maximal
      treadmill exercise tests with metabolic and heart rate measurements. Maximal
      heart rate and the CRI were considered main outcomes. RESULTS: The peak oxygen
      consumption (41.7 vs 31.8mL. kg(-1).min(-1)) and peak heart rate (165+/-14.7 vs
      192+/-7.7 beats/min) were significantly lower in participants with DS than in
      controls (P<.05). The CRI was below normal (.84+/-.25) in participants with DS
      and was normal (.97+/-.07) in controls. CONCLUSION: Both the CRI and the peak
      heart rates were indicative of chronotropic incompetence in participants with DS,
      but not in controls. The CRI of the participants with DS was similar to that
      reported for nondisabled populations who have a true chronotropic response to
      exercise. The CRI indicated that the low peak heart rate in our participants with
      DS was a true chronotropic response.

PMID- 14639559
TI  - The influence of early aerobic training on the functional capacity in patients
      with cerebrovascular accident at the subacute stage.
AB  - OBJECTIVE: To investigate the effect of early aerobic training on the aerobic and
      functional abilities of patients in the subacute stage of cerebrovascular
      accident (CVA). DESIGN: Randomized controlled trial. SETTING: Rehabilitation unit
      in Israel. PARTICIPANTS: Ninety-two patients who had a first CVA were randomly
      assigned to an exercise-training group or to a control group. INTERVENTION:
      Aerobic training with a leg cycle ergometer for 8 weeks. MAIN OUTCOME MEASURES:
      Workload, exercise time, resting and submaximal blood pressure and heart rate,
      and functional abilities. RESULTS: A trend toward improvement was found in all
      aerobic parameters for the experimental group, but only heart rate at rest
      (P=.02), workload, and work time (P<.01) improved significantly. A trend for
      improvement was also found in all parameters of function for the experimental
      group, but only stair climbing was significantly better (P<.01). An interaction
      (95% confidence interval, 1.7-17.21) was found between age and aerobic training
      on walking distance. Although no significant effect was found in the group of
      younger patients (aged <65y), a significant difference in favor of training was
      noted in the group of older patients. CONCLUSIONS: Patients with CVA in the
      subacute stage improved some of their aerobic and functional abilities after
      submaximal aerobic training.

PMID- 14639560
TI  - Shoulder magnetic resonance imaging abnormalities, wheelchair propulsion, and
      gender.
AB  - OBJECTIVE: To investigate the relationship between pushrim forces and the
      progression of shoulder injuries in manual wheelchair users. DESIGN: Longitudinal
      case series. SETTING: Biomechanics laboratory and magnetic resonance imaging
      (MRI) facility at a Veterans Health Administration medical center and university
      hospital, respectively. PARTICIPANTS: Fourteen individuals with spinal cord
      injury (8 men, 6 women) who used manual wheelchairs. INTERVENTION: Subjects
      propelled their own wheelchairs on a dynamometer at 0.9 and 1.8m/s. Bilateral
      biomechanical data were obtained by using force and moment sensing pushrims at
      time 1. Bilateral shoulder MR images were also completed on 2 occasions, at time
      1 and, approximately 2 years later, at time 2. MAIN OUTCOME MEASURES: The peak
      pushrim forces in a pushrim coordinate system were calculated, weight normalized
      and averaged over 5 strokes (presented as % body weight). MRI abnormalities were
      graded by using a summated scale. Differences between scores between times 1 and
      2 were calculated. RESULTS: Subjects were divided into 2 groups based on change
      in MRI score. Seven subjects were in the group with worsening scores (MRI+; mean,
      8.14 points; range, 5-16), and 7 were in the group with improving or unchanging
      scores (MRI-; mean, -1.00 point; range, -5 to 1). There was no significant
      difference between groups with respect to age, body mass index, or years from
      injury. There were significantly more women in the MRI+ group (6 women, 1 man)
      than in the MRI- group (7 men) (P=.001). The MRI+ group used significantly
      greater weight-normalized radial force, or force directed toward the axle at time
      1, to propel their wheelchairs at each speed (P<.01): MRI+ at 0.9m/s (mean radial
      force +/- standard deviation, 5.2%+/-1.0%) and MRI- at 0.9m/s (mean radial force,
      3.2%+/-1.7%) (P=.028); and MRI+ at 1.8m/s (mean radial force, 6.6%+/-1.2%)
      (P=.023) and MRI- at 1.8m/s (mean radial force, 4.1%+/-2.2%). In a separate
      analysis, women were found to propel with a significantly higher radial force. A
      logistic regression found a significant relationship between radial force at time
      1 and increased risk of progression of MRI findings over time. CONCLUSION:
      Individuals who propel with a greater percentage of force directed toward the
      axle were at increased risk of progression of MRI findings over time. Most people
      in this group were women. Clinicians should instruct wheelchair users in
      effective propulsion techniques and should pay particular attention to women who
      use wheelchairs. Reducing forces during wheelchair propulsion may minimize the
      likelihood of developing shoulder injuries.

PMID- 14639561
TI  - Depression assessment after traumatic brain injury: an empirically based
      classification method.
AB  - OBJECTIVES: To describe the patterns of depression in patients with traumatic
      brain injury (TBI), to evaluate the psychometric properties of the
      Neurobehavioral Functioning Inventory (NFI) Depression Scale, and to classify
      empirically NFI Depression Scale scores. DESIGN: Depressive symptoms were
      characterized by using the NFI Depression Scale, the Beck Depression Inventory
      (BDI), and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Depression
      Scale. SETTING: An outpatient clinic within a Traumatic Brain Injury Model
      Systems center. PARTICIPANTS: A demographically diverse sample of 172 outpatients
      with TBI, evaluated between 1996 and 2000. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The NFI, BDI, and MMPI-2 Depression Scale. The Cronbach alpha,
      analysis of variance, Pearson correlations, and canonical discriminant function
      analysis were used to examine the psychometric properties of the NFI Depression
      Scale. RESULTS: Patients with TBI most frequently reported problems with
      frustration (81%), restlessness (73%), rumination (69%), boredom (66%), and
      sadness (66%) with the NFI Depression Scale. The percentages of patients
      classified as depressed with the BDI and the NFI Depression Scale were 37% and
      30%, respectively. The Cronbach alpha for the NFI Depression Scale was.93,
      indicating a high degree of internal consistency. As hypothesized, NFI Depression
      Scale scores correlated highly with BDI (r=.765) and MMPI-2 Depression Scale T
      scores (r=.752). The NFI Depression Scale did not correlate significantly with
      the MMPI-2 Hypomania Scale, thus showing discriminant validity. Normal and
      clinically depressed BDI scores were most likely to be accurately predicted by
      the NFI Depression Scale, with 81% and 87% of grouped cases, respectively,
      correctly classified. Normal and depressed MMPI-2 Depression Scale scores were
      accurately predicted by the NFI Depression Scale, with 75% and 83% of grouped
      cases correctly classified, respectively. Patients' NFI Depression Scale scores
      were mapped to the corresponding BDI categories, and 3 NFI score classifications
      emerged: minimally depressed (13-28), borderline depressed (29-42), and
      clinically depressed (43-65). CONCLUSIONS: Our study provided further evidence
      that screening for depression should be a standard component of TBI assessment
      protocols. Between 30% and 38% of patients with TBI were classified as depressed
      with the NFI Depression Scale and the BDI, respectively. Our findings also
      provided empirical evidence that the NFI Depression Scale is a useful tool for
      classifying postinjury depression.

PMID- 14639562
TI  - Reliability of peak cardiorespiratory responses in patients with moderate to
      severe traumatic brain injury.
AB  - OBJECTIVE: To examine the test-retest reliability of acute physiologic responses
      in patients with traumatic brain injury (TBI). DESIGN: Repeated measures within 1
      week. SETTING: Brain injury rehabilitation program and community rehabilitation
      hospital. PARTICIPANTS: Thirty-six inpatients or their legal guardians.
      INTERVENTIONS: Each patient performed a symptom-limited incremental cycle
      ergometer test to voluntary fatigue on 2 separate occasions within 1 week. MAIN
      OUTCOME MEASURES: Peak values of power output and cardiorespiratory responses
      measured with a metabolic cart interfaced with an electrocardiogram. RESULTS:
      Intraclass correlations between the 2 trials were as follows: power output,.96;
      absolute oxygen uptake,.98; relative oxygen uptake,.97; heart rate,.82;
      ventilation rate,.96; and respiratory exchange ratio,.81. Bland-Altman plots
      showed that all data points were within the 95% confidence limits of the mean
      value of the 2 trials for each variable. CONCLUSIONS: The reliability of the peak
      cardiorespiratory responses during non-weight-bearing exercise was high in
      patients with TBI in a controlled laboratory setting. Therefore, aerobic exercise
      programs can be accurately prescribed, and changes resulting from such
      interventions can be confidently evaluated in this population.

PMID- 14639563
TI  - Posttraumatic hydrocephalus: a clinical, neuroradiologic, and neuropsychologic
      assessment of long-term outcome.
AB  - OBJECTIVES: To detect the clinical and radiologic characteristics of
      posttraumatic hydrocephalus (PTH), to define its prognostic value, and to assess
      the effects of shunt surgery. DESIGN: Correlational study on a prospective
      cohort. SETTING: Brain injury rehabilitation center. PARTICIPANTS: One hundred
      forty patients with severe traumatic brain injury (TBI) referred to an inpatient
      intensive rehabilitation unit of primary care in a university-based system.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Glasgow Outcome Scale
      (GOS), Disability Rating Scale (DRS), FIM instrument, and Neurobehavioural Rating
      Scale (NRS), as well as single-photon emission computed tomography (SPECT) and
      magnetic resonance imaging. RESULTS: PTH was found in 45% of patients. Risk
      factors for PTH were as follows: age (P<.04), duration of coma (P<.0001), and
      decompressive craniectomy (P<.0001). PTH correlated with the degree of
      hypoperfusion in the temporal lobes (P<.001). Patients who showed clinical
      deterioration improved after surgery. PTH correlated significantly with GOS, DRS,
      FIM, and NRS (P<.0001) 1 year after the trauma, and it influenced the appearance
      of posttraumatic epilepsy (P<.02). CONCLUSIONS: PTH concerns about 50% of
      patients with severe TBI. It influences functional and behavioral outcome and the
      appearance of posttraumatic epilepsy. The selection of patients for surgery can
      be defined principally on a clinical basis. SPECT may be helpful for
      differentiating ventricular enlargement due to cortical atrophy and
      hydrocephalus.

PMID- 14639564
TI  - Rehabilitation needs of an inpatient medical oncology unit.
AB  - OBJECTIVE: To identify prospectively functional impairments and rehabilitation
      needs in an acute care medical oncology unit. DESIGN: Prospective cohort study.
      SETTING: Inpatient medical oncology unit at a Veterans Affairs hospital.
      PARTICIPANTS: Fifty-five patients admitted over a 6-month period. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: FIM instrument, functionally based
      physical examination, Rehabilitation Needs Assessment, and Recreational Needs
      Assessment. RESULTS: On admission, the mean FIM total score was 105 out of 126,
      the FIM motor score was 72 out of 91, and the FIM cognitive score was 34 out of
      35. The functionally based physical examination did not generally correlate with
      scores obtained on the FIM. Forty-eight (87%) patients had rehabilitation needs
      on admission. Forty-six (84%) patients had rehabilitation needs on discharge.
      Rehabilitation Needs Assessment on admission showed deconditioning in 42 (76%)
      patients; mobility impairment in 32 (58%) patients; a significant decrease in
      range of motion in 23 (42%) patients; deficits in activities of daily living in
      12 (22%) patients; a need for recreational therapy in 7 (13%) patients; potential
      for benefit from patient education in 30 (55%) patients; and a need for
      modalities, edema control, or wound care in fever than 5% of patients. The most
      commonly requested recreational activity was reading. CONCLUSIONS: Patients
      admitted to inpatient medical oncology units have many unmet, remediable
      rehabilitation needs that may not be recognized by nonrehabilitation physicians
      and other clinical staff. These findings suggest that assessment of medical
      oncology patients may be enhanced by consultation with rehabilitation medicine
      specialists.

PMID- 14639565
TI  - Predicting the achievement of 6 grades of physical independence from data
      routinely collected at admission to rehabilitation.
AB  - OBJECTIVE: To develop prognostic indexes with which to establish the likelihood
      of individuals achieving specific grades of physical independence by the
      conclusion of inpatient rehabilitation. DESIGN: Logistic regression with
      prospective validation. SETTING: Five hundred sixty inpatient rehabilitation
      facilities. PARTICIPANTS: Records of 218,290 adults discharged in 1995 were used
      to establish the grades and the indexes predicting those grades. There were
      259,806 1997 discharges included in the validation. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Six physical independence grades reflecting
      the most likely profiles of performance across the 13 motor FIM items. RESULTS:
      After severity adjustment, patients 65 years of age or younger, compared with
      those 84 years of age or older, had odds ratios of reaching higher grades ranging
      from 1.5 (95% confidence interval [CI], 1.4-1.7) to 7.5 (95% CI, 4.3-13.1).
      Admission to rehabilitation within 2 weeks of disability was associated with more
      favorable prognoses. Areas under the receiver operating characteristic curve
      ranged from.80 to.94 for the indexes, with minimal shrinkage on prospective
      validation. CONCLUSION: The models have sufficient reliability to establish from
      admission information the likelihood that a patient will achieve a specific grade
      of physical independence by the time of discharge from rehabilitation. The
      capacity to quantify prognosis has clinical, policy, and research applications.

PMID- 14639566
TI  - Does increased prosthetic weight affect gait speed and patient preference in
      dysvascular transfemoral amputees?
AB  - OBJECTIVES: To determine if increased prosthetic weight affects gait speed in
      dysvascular transfemoral amputees and to see if there is any patient preference
      for lighter versus heavier prostheses. DESIGN: Randomized prospective double
      blind crossover trial. SETTING: Outpatient, tertiary care, amputee clinic in
      Ontario, Canada. PARTICIPANTS: A convenience sample of 10 subjects with
      unilateral transfemoral amputations because of peripheral vascular disease. All
      subjects were independent community ambulators over 50 years old. INTERVENTION:
      Seemingly identical weights of 150g (placebo weight), 770g, and 1625g were added
      to the prosthesis 14cm below the knee joint. MAIN OUTCOME MEASURES: Two-minute
      walk test (2MWT) and subject preference. RESULTS: The 2MWT results were not
      significantly influenced by weight added (mean, 53.4+/-28.4m, 55.1+/-28.9m, and
      52.8+/-26.7m for 150g, 770g, and 1625g of added weight, respectively). Subject
      preference revealed that more than half preferred a weighted prosthesis over the
      "placebo" weight (5 subjects preferred 770g added, 4 subjects preferred 150g
      added, 1 preferred 1625g added). CONCLUSIONS: Short-term intervention with
      increased prosthetic mass had no significant adverse affect on gait speed, and
      more than half of the subjects preferred an added mass condition.

PMID- 14639567
TI  - Discharge destination after dysvascular lower-limb amputations.
AB  - OBJECTIVE: To examine postacute care rehabilitation services use after
      dysvascular amputation. DESIGN: State-maintained hospital discharge data from the
      Maryland Health Services Cost Review Commission were analyzed. SETTING: Maryland
      statewide hospital discharge database. PARTICIPANTS: Persons discharged from
      nonfederal acute care hospitals from 1986 to 1997 with a procedure code for lower
      limb amputation (ICD-9-CM code 84.12-.19), excluding toe amputations. Those
      persons with amputations due to trauma, bone malignancy, or congenital anomalies
      were excluded. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Postacute
      care service utilization. RESULTS: There were 16,759 discharges with an
      amputation procedure over this period. The average age was 69.3+/-14.3 years, and
      51.9% were men. Black persons comprised 42.4% of the sample. Diabetes was present
      in 42.0%, and peripheral vascular disease was noted for 66.1% of amputees.
      Amputations were at the foot (19.4%), transtibial (38.1%), and transfemoral
      (42.4%) levels. The largest proportion (40.6%) of patients was discharged
      directly home after acute care, 37.4% went to a nursing home, 9.2% went home with
      home care, and 9.6% were discharged to an inpatient rehabilitation unit. From
      1986 to 1997, there were downward trends in the rate of discharges directly home
      and corresponding upward trends in nursing home and inpatient rehabilitation
      dispositions. CONCLUSIONS: Inpatient rehabilitation use is infrequent after
      dysvascular amputation. Prospective studies are necessary to examine outcomes for
      persons receiving rehabilitation services in different care settings to define
      the optimal rehabilitation venue for functional restoration.

PMID- 14639568
TI  - Clinical tests for the evaluation of postural instability in patients with
      parkinson's disease.
AB  - OBJECTIVE: To determine which test for postural instability in Parkinson's
      disease (PD) is reliable, valid, and easy to perform in a clinical setting.
      DESIGN: Cross-sectional reliability and validity study. SETTING: Academic center
      for movement disorders. PARTICIPANTS: Forty-two patients with PD and 15 controls.
      Based on the results of a structured interview, the patients were divided in PD
      unstable (n=22) and PD-stable (n=20) groups. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Several variants of the retropulsion test with differences in
      execution and scoring. Responses were scored on 5 different rating scales
      (ratings of Nutt, Bloem, Pastor; the Unified Parkinson's Disease Rating Scale
      [UPDRS]; the Short Parkinson Evaluation Scale). These tests were compared with
      steady-stance positions. RESULTS: The interrater reliability was high for most
      ratings, with weighted kappa ranging from.63 for the UPDRS to.98 for both the
      Pastor rating and steady-stance positions. Most ratings distinguished between the
      groups. However, the Nutt rating had the highest overall predictive accuracy,
      with a sensitivity of.63 and a specificity of.88. CONCLUSIONS: The most valid
      test for postural stability in PD was an unexpected shoulder pull, executed once,
      with taking more than 2 steps backward considered abnormal. This retropulsion
      test is easy to use in a clinical setting.

PMID- 14639569
TI  - Prevalence of vitamin B12 deficiency in spinal cord injury.
AB  - OBJECTIVE: To assess the prevalence of vitamin B(12) deficiency in persons with
      spinal cord injury (SCI) or disease (SCD). DESIGN: Cross-sectional study with
      prospective blood collection and retrospective medical record review. SETTING:
      Regional Veterans Affairs SCI service. PARTICIPANTS: One hundred six adult men
      with chronic SCI or SCD and without other acute medical or surgical
      complications; most had SCI or SCD due to trauma or cervical spinal stenosis.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fasting blood samples were
      obtained at annual evaluation for serum B(12), folic acid, methylmalonic acid
      (MMA), and homocysteine. Serum levels were analyzed graphically and associated
      with patient variables by using statistical tests. RESULTS: The vitamin B(12)
      level was subnormal in 5.7% of subjects; of those, all had supranormal MMA
      levels, all were age 40 to 59, most had complete SCI, and 67% had symptoms
      suggestive of B(12) deficiency. Low-normal B(12) levels were associated with a
      high prevalence of supranormal MMA. Subjects with either subnormal B(12) or low
      normal B(12) with supranormal MMA, both suggestive of vitamin B(12) deficiency,
      comprised 13.3% of the total group of subjects. CONCLUSION: Vitamin B(12)
      deficiency is most common in middle-aged SCI or SCD persons with complete or near
      complete spinal cord involvement (ie, American Spinal Injury Association class A
      C injuries). Treatment with either parenteral or oral B(12) replacement may
      optimize health and prevent irreversible neuropsychiatric complications in those
      with subnormal and low-normal B(12) levels.

PMID- 14639570
TI  - Effects of functional knee bracing on muscle-firing patterns about the chronic
      anterior cruciate ligament-deficient knee.
AB  - OBJECTIVE: To examine the effects of functional knee bracing on the muscle-firing
      patterns about the chronic anterior cruciate ligament (ACL)-deficient knee in
      successful brace users. DESIGN: Cross-sectional comparative clinical trial.
      SETTING: Motion analysis laboratory. PARTICIPANTS: Ten active individuals with
      unilateral, isolated, chronic (>18mo postinjury), ACL-deficient knees who
      subjectively reported improved function with a functional knee bracing.
      INTERVENTION: Each subject completed 3 single-leg hop maneuvers on their ACL
      deficient knee with and without their knee brace while surface electromyographic
      activity was recorded from the quadriceps, hamstring, and gastrocnemius muscles.
      MAIN OUTCOME MEASURES: Muscle onset latency. RESULTS: Brace use significantly
      delayed the average onset of vastus lateralis activation before landing (123+/
      47ms vs 109+/-30ms, P<.001), though significant interindividual variations
      existed. Bracing significantly altered the onset latency in 1 or more muscles in
      9 of 10 subjects. In 4 subjects, a favorable change in the firing pattern was
      seen, whereas only 1 subject exhibited an unfavorable change. Without bracing, 5
      of the 10 subjects fired the hamstrings or gastrocnemius muscles first; with
      bracing, 7 of 10 fired these muscles first. CONCLUSIONS: Brace use in this
      population did not consistently result in more favorable muscle firing patterns
      during the single-leg hop maneuver. Interindividual responses to brace use
      indicate the need for further research to investigate the multiple strategies
      that may exist to stabilize the ACL-deficient knee. In the meantime, functional
      knee brace use among ACL-deficient patients remains empirical.

PMID- 14639571
TI  - Benefit of inpatient multidisciplinary rehabilitation up to 1 year after stroke.
AB  - OBJECTIVE: To analyze the benefit of inpatient multidisciplinary rehabilitation
      up to 1 year after stroke. DESIGN: Retrospective cohort study. SETTING: Inpatient
      rehabilitation hospital in Japan. PARTICIPANTS: A total of 1056 patients with
      stroke were divided into 3 groups based on the interval between stroke onset and
      admission to the rehabilitation hospital: group I, within 90 days (n=507, 48%);
      group II, 91 to 180 days (n=377, 36%); and group III, more than 180 days (n=172,
      16%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional outcome (A
      to D; independent to totally dependent) in walking, affected upper extremity, and
      activities of daily living (ADLs) and discharge disposition. RESULTS: Walking
      status improved in 70.9% of nonambulatory patients in group I, in 54.8% in group
      II, and in 43.9% in group III. Similarly, ADLs improved in 66.7% of the totally
      dependent patients in group I and in approximately 50% in groups II and III.
      Functional gain in those with a totally nonfunctional upper extremity at
      admission was poor (29.7%). Initial functional categories affected each outcome
      (P<.0001). On discharge, 73.8% in group I and approximately 60% in groups II and
      III went home. CONCLUSION: Approximately half of all patients regained their
      abilities in walking and ADLs after inpatient multidisciplinary rehabilitation up
      to 1 year after stroke. However, there was considerable limitation in functional
      recovery of the affected upper extremity.

PMID- 14639572
TI  - Rehabilitation of somatic sensation and related deficit of motor control in
      patients with pure sensory stroke.
AB  - OBJECTIVE: To assess the effectiveness of a rehabilitative training program for
      deficits in somatic sensation and motor control of the hand in patients with pure
      sensory stroke. DESIGN: Multiple baseline and before-after follow-up trial with
      behavioral analysis of single cases. SETTING: Rehabilitation unit of a university
      hospital in Italy. PARTICIPANTS: Four patients were studied: 2 had a unilateral
      lesion confined to the parietal lobe (patients 1, 2), and 2 had a unilateral
      lesion of the thalamus (patients 3, 4) that also lapped the posterior limb of the
      internal capsule. All 4 patients had chronic deficits in somatic sensation and
      motor control of the contralesional hand. INTERVENTION: Behavioral training
      consisting of exercises aimed at improving somatic sensation and motor control of
      the affected, contralesional hand. Thirty treatment sessions, each lasting 50
      minutes, were performed. MAIN OUTCOME MEASURES: Somatic deficit was evaluated
      with 5 tests, and motor control deficit was assessed with 4 tests. One functional
      test estimated the influence of somatic deficit on daily activities. A visual
      analog scale (VAS) was also submitted to the patients' relatives to evaluate the
      amount of use of the affected arm in daily life activities. A baseline was
      obtained by recording each measure, except for the VAS, 4 times at the first
      evaluation session. Evaluation sessions were conducted before, after, and 6
      months after the end of the experimental treatment. RESULTS: All patients showed
      a stable baseline in at least 8 of the outcome measures. Patients 1 and 2
      significantly improved in 9 and 7 outcome measures, respectively. Patients 3 and
      4 improved in 4 and 7 outcome measures, respectively. With the exception of case
      3, all patients considerably increased their use of the affected arm during daily
      life. The improvement was generally stable over a 6-month period, suggesting that
      the treatment had a long-term effect. CONCLUSIONS: Results suggest the possible
      effectiveness of our training program for treating somatic and motor control
      deficits of the hand in patients with cortical or subcortical pure sensory
      stroke.

PMID- 14639573
TI  - A model to aid in the prediction of discharge location for stroke rehabilitation
      patients.
AB  - OBJECTIVE: To determine which demographic and medical factors recorded on
      admission to a rehabilitation unit best predict discharge accommodation outcomes.
      DESIGN: Retrospective chart review. SETTING: Inpatient rehabilitation unit in an
      academic hospital in southwestern Ontario, Canada. PARTICIPANTS: One hundred four
      stroke patients (54 women, 50 men; mean age, 72.0y) admitted to the
      rehabilitation unit over a 4-year period. INTERVENTIONS: All patients underwent
      evaluations by the physical therapy, occupational therapy, social work, speech
      pathology, and psychology departments. Patients were divided into 2 groups: (1)
      no change in premorbid accommodation and (2) change in premorbid accommodation.
      MAIN OUTCOME MEASURES: Demographic, clinical, and housing information (premorbid,
      discharge) and functional data (FIM trade mark instrument, Chedoke-McMaster
      Stroke Assessment [CMSA] Impairment Inventory, Berg Balance Scale [BBS]) were
      recorded for each patient. RESULTS: Of 104 patients, 24 were discharged with a
      change in premorbid accommodation. Change in discharge location was significantly
      associated with age, gender, and the presence of premorbid social support
      (P<.01), but not with type of premorbid living arrangement. Statistically
      significant differences were noted between total FIM scores (P<.001), BBS scores
      (P<.001), and the postural component of the CMSA Impairment Inventory (P<.03). A
      logistic regression model, predicting 67% of the variance, was created to predict
      discharge accommodations. CONCLUSIONS: Patients admitted to the rehabilitation
      unit can be scored to obtain their predicted chance of being discharged with a
      change from their premorbid accommodations. The equation is relatively easy to
      calculate and is based on data that are commonly collected in rehabilitation.

PMID- 14639574
TI  - Satisfaction of members of interdisciplinary rehabilitation teams with goal
      planning meetings.
AB  - OBJECTIVE: To study how satisfied members of interdisciplinary rehabilitation
      teams are with goal planning meetings. DESIGN: Survey. SETTING: A regional
      rehabilitation center for people with acute nonprogressive brain injuries in the
      United Kingdom. PARTICIPANTS: Forty-four rehabilitation professionals who
      participated in 31 goal-planning meetings held between January 1, 2001, and March
      30, 2001. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Responses to a
      questionnaire about staff satisfaction with rehabilitation team meetings.
      RESULTS: Forty-four of 46 members of 21 different rehabilitation teams completed
      the questionnaires. They included 12 occupational therapists, 7 physiotherapists,
      7 physicians, 6 nurses, 5 clinical psychologists, 5 speech pathologists, and 2
      social workers. Median scores of different domains were as follows:
      participation, 13; behavior, 20; outcome, 14; and process, 16. Correlations
      between the participation and outcome domains (rho=.731, P=.01) and the process
      and outcome domains (rho=.384, P=.05) were significant. None of the domain scores
      correlated with features of the meetings. Scores given by chairpersons for
      participation (P=.001) and outcome (P=.047) were significantly higher than those
      given by other participants. CONCLUSIONS: Professionals were satisfied with the
      behavior of other participants and the process of goal-planning meetings.
      Satisfaction with outcome was related to satisfaction with the participation in
      and the process of the meetings. Chairpersons were more satisfied with the
      participation domain.

PMID- 14639575
TI  - Fatigue associated with stroke and other neurologic conditions: Implications for
      stroke rehabilitation.
AB  - OBJECTIVES: To examine the general phenomenon of fatigue in stroke and other
      neurologic disorders and to review what is currently known about its occurrence,
      including its frequency, duration, severity, and associated factors, to develop a
      strategy for treatment. DATA SOURCES: Computerized databases (eg, PubMed,
      PsycInfo, Science Citation Index, Ovid EMBASE, Ovid MEDLINE) searched from
      inception to May 2002. Additional references were identified from bibliographies
      of pertinent articles and books. STUDY SELECTION: Over 1000 articles were
      identified as relevant to fatigue experienced by patients with neurologic or
      nonneurologic disorders. Articles on fatigue in stroke and neurologic disorders,
      mechanisms, and/or treatment were selected for inclusion. DATA EXTRACTION:
      Authors reviewed the articles and assessed the purpose, study design, and
      conclusions for validity and relevance to the topic of fatigue in stroke. DATA
      SYNTHESIS: Fatigue is a common complaint among patients with neurologic disorders
      including stroke. Few studies have documented the high frequency of fatigue in
      poststroke patients and its negative impact on daily functioning and quality of
      life. Little is known about associated factors or about therapeutic strategies
      that may be used to alleviate it. Examination of fatigue in other neurologic
      populations suggests common characteristics and associated factors that may be
      useful in the development of potential therapeutic strategies. Pharmacologic and
      nonpharmacologic therapeutic interventions, such as stimulants, amantadine, or
      sleep and stress-management education, have been used with some success in
      neurologic and other patient populations (eg, multiple sclerosis, human
      immunodeficiency virus, acquired immune deficiency syndrome, cancer), but
      evidence of effectiveness based on randomized clinical trials is rare.
      CONCLUSIONS: Poststroke fatigue is common. Therapeutic strategies have been used
      to treat fatigue in other patient populations, but it is unclear whether these
      will be beneficial to poststroke patients. Frequency, severity, duration, impact,
      predisposing factors, and causes of poststroke fatigue, as well as the
      development of effective treatment, require further research. Criteria for
      assessment of fatigue and potential therapeutic interventions are outlined as a
      first step for stimulating further research.

PMID- 14639576
TI  - Comparison between successful and failed sit-to-stand trials of a patient after
      traumatic brain injury.
AB  - OBJECTIVE: To compare the peak whole-body center of mass (COM) velocities and
      joint angular contributions in successful and unsuccessful sit-to-stand (STS)
      trials in a subject with traumatic brain injury (TBI). DESIGN: Single-case study.
      SETTING: Motion research laboratory. PARTICIPANT: A 24-year-old man who was 3.5
      years post-TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak
      horizontal and vertical velocities of the whole-body COM and peak angular
      velocities of the ankle, knee, hip, and shoulder joints. RESULTS: The peak whole
      body COM vertical velocity was significantly lower in the unsuccessful STS
      trials. Angular velocities at the hip, knee, ankle, and shoulder joints in
      successful trials exceeded those in unsuccessful trials (P<.001). The subject's
      peak knee extension velocity was the single major predictor of the peak whole
      body COM vertical velocity (r(2)=.90). Knee extension angular velocities greater
      than 3.25 radian/s were associated with successful STS trials. Knee extension
      angular velocities between 2.75 and 3.25 radian/s were associated with successful
      rising 50% of the time; the subject had no success in rising when velocities were
      less than 2.75 radian/s. CONCLUSIONS: For this subject, sit-back failures
      occurred in STS attempts characterized by peak whole-body COM vertical velocities
      that were lower than those generated in successful rising trials. These
      unsuccessful rising attempts were primarily the result of the subject's inability
      to generate sufficient knee extension angular velocity.

PMID- 14639578
TI  - Ethics and the disabled.

PMID- 14639579
TI  - Who is the primary suspect in acute motor axonal neuropathy?

PMID- 14639580
TI  - Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies.
AB  - The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and
      sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector
      response appears to be humoral and directed against the microvasculature, whereas
      in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade and
      eventually destroy nonnecrotic muscle fibers expressing major histocompatibility
      complex class I. The need for more specific and safer therapies in inflammatory
      myopathies has prompted researchers to better decipher the molecular events
      associated with inflammation and muscle fiber loss in these diseases. The complex
      specific migration of leukocyte subsets to target tissues requires a coordinated
      series of events, namely activation of leukocytes, adhesion to the vascular
      endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a
      major role in this multistep process. In addition, cytokines by stimulating CAM
      expression and orchestrating T-cell differentiation also influence the immune
      response. This review focuses on recent advances in defining the molecular events
      involved in leukocyte trafficking in inflammatory myopathies. Specific topics
      include a concise summary of clinical features, pathological findings and
      immunopathology observed in inflammatory myopathies, background information about
      cytokines, chemokines and cell adhesion molecules, and the expression of these
      molecules in inflammatory myopathies.

PMID- 14639581
TI  - The refractory period of transmission is impaired in axonal Guillain-Barre
      syndrome.
AB  - Guillain-Barre syndrome (GBS) is classified as acute motor axonal neuropathy
      (AMAN) or acute inflammatory demyelinating polyneuropathy (AIDP). Motor nerve
      conduction block is frequently found in both subtypes of GBS. To compare patterns
      of conduction block and the safety factor for impulse transmission in AMAN and
      AIDP, pairs of supramaximal stimuli at intervals of 1-5 ms were delivered to
      stimulate the median nerve at the wrist. At the 2- and 3-ms intervals, compound
      muscle action potentials (CMAPs) to the second stimulus were significantly
      smaller in AMAN patients (n = 7) than in normal subjects (n = 10) and AIDP
      patients (n = 6). Over 4 weeks from onset, the amplitude of both conditioned and
      unconditioned CMAPs returned toward normal, consistent with improvement in the
      safety factor for impulse transmission. The refractory period of transmission is
      impaired in AMAN, and the site of transmission failure is likely to be the motor
      nerve terminals. In addition to axonal degeneration, the critically but
      reversibly reduced safety factor is important in the pathophysiology of AMAN, and
      consistent with the rapid resolution of distal conduction block often seen in
      AMAN patients.

PMID- 14639582
TI  - Prevalence and progression of mitochondrial diseases: a study of 50 patients.
AB  - We report 50 patients with various clinical phenotypes of mitochondrial disease
      studied over the past 10 years in a large urban area (Madrid Health Area 5). The
      clinical phenotypes showed a large variety of abnormalities in molecular biology
      and biochemistry. The prevalence of mitochondrial diseases was found to be 5.7
      per 100,000 in the population over 14 years of age. Clinical and
      electrophysiological assessment reveal signs of neuropathy in 10 patients.
      Electromyographic findings consistent with myopathy were obtained in 37 cases.
      Six patients died of medical complications. Disease phenotype influenced survival
      to some degree (P < 0.01). Age of onset and gender were not associated with
      differences in survival. Mitochondrial disease is thus far more common than
      expected and a common cause of chronic morbidity.

PMID- 14639583
TI  - Atypical presentations of primary amyloid neuropathy.
AB  - Primary amyloidosis (AL) may be complicated by peripheral neuropathy in 15-35% of
      cases. We report on four patients with atypical neurological presentations of AL
      neuropathy, whose diagnoses were delayed due to varied clinical presentations.
      The clinical presentation included painful sensory neuropathy (two patients),
      mononeuropathy multiplex (one patient), and primary demyelinating polyneuropathy
      (one patient). The latter two types of presentation have not been reported
      previously. The diagnosis was established by fat pad biopsy in two patients,
      lymph node biopsy in one, and sural nerve biopsy in one. Two patients were
      treated with high-dose melphalan followed by stem cell rescue, and one was
      treated with oral melphalan and prednisone. All three cases experienced
      stabilization of neuropathic symptoms. We report these cases in order to raise
      awareness of the varied clinical presentation of AL neuropathy.

PMID- 14639584
TI  - Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry
      disease.
AB  - Fabry disease is an X-linked disorder caused by a deficiency of lysosomal alpha
      galactosidase A resulting in accumulation of alpha-D-galatosyl conjugated
      glycosphingolipids. Clinical manifestations include a small-fiber neuropathy
      associated with debilitating pain and hypohidrosis. We report the effect of a 3
      year open-label extension of a previously reported 6-month placebo-controlled
      enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry
      disease received 0.2 mg/kg of alpha-galactosidase A every 2 weeks. The effect of
      ERT on neuropathic pain scores while off pain medications, quantitative sensory
      testing, quantitative sudomotor axon reflex test (QSART), and thermoregulatory
      sweat test (TST) is reported. In the patients who crossed-over from placebo to
      ERT (n = 10), mean pain-at-its-worst scores on a 0-10 scale decreased (from 6.9
      to 4.5). There was a significant reduction in the threshold for cold and warm
      sensation in the foot. At the 3-year time-point, pre-ERT sweat excretion in 17
      Fabry patients was 0.24 +/- 0.33 microl/mm(2) vs. 1.05 +/- 0.81 in concurrent
      controls (n = 38). Sweat function improved 24-72 h post-enzyme infusion (0.57 +/-
      0.71 microl/mm(2)) and normalized in four anhidrotic patients. TST confirmed the
      QSART results. We conclude that prolonged ERT in Fabry disease leads to a modest
      but significant improvement in the clinical manifestations of the small-fiber
      neuropathy associated with this disorder. QSART may be useful to further optimize
      the dose and frequency of ERT.

PMID- 14639585
TI  - Preserved cutaneous silent periods in severe entrapment neuropathies.
AB  - Noxious digital nerve stimulation during isometric contraction of hand muscles
      leads to transient suppression of the electromyographic activity, the so-called
      cutaneous silent period (CSP), which is mostly due to a spinal reflex mediated by
      A-delta fibers. We investigated two patients with carpal tunnel syndrome (CTS)
      and two patients with ulnar entrapment at the elbow (UNE), in whom routine
      sensory conduction studies failed to document afferent fiber continuity across
      the lesion site. In three patients, motor nerve conduction studies and
      electromyography failed to demonstrate intact efferent fibers. Noxious
      stimulation of digit II elicited distinct CSPs in ulnar-innervated hand muscles
      in both patients with CTS, and stimulation of digit V evoked CSPs in median
      innervated hand muscles in both UNE patients. The presence of a CSP can only be
      explained by preserved A-delta fibers crossing the respective lesion site. Thus,
      preserved CSPs may serve to document residual nerve continuity in severe
      entrapment neuropathies when fast-conducting fibers are so compromised that their
      continuity cannot be detected by standard electrodiagnostic techniques.

PMID- 14639586
TI  - Gelsolin-related familial amyloidosis, Finnish type, in a Portuguese family:
      clinical and neurophysiological studies.
AB  - We report a Portuguese family with familial amyloid polyneuropathy related to
      gelsolin. There were no known Finnish ancestors, but the same mutation as
      described in Finnish patients (G654A) was carried. Clinical and
      neurophysiological investigations were performed in four patients. Corneal
      lattice dystrophy affected all four patients; an axonal lesion of the facial
      nerve occurred in three patients; visual tract involvement was documented in one
      case; and corticospinal and posterior column dysfunction was present in one
      patient. Polarizing microscopy of skin and muscle samples demonstrated amyloid
      deposits in two patients; anti-gelsolin immunohistochemistry was positive for
      amyloidogenic gelsolin. The Finnish mutation of gelsolin protein (G654A) was
      detected in five family members. The utility of neurophysiological testing in the
      evaluation and follow-up of this type of amyloidosis is discussed.

PMID- 14639587
TI  - Characterization of two new dominant ClC-1 channel mutations associated with
      myotonia.
AB  - Voltage-gated ClC-1 chloride channels encoded by the CLCN1 gene have a major role
      in setting the membrane potential in skeletal muscle. More than 60 CLCN1
      mutations have been associated with myotonia congenita. These mutations are
      traditionally classified as recessive (Becker's disease) or dominant (Thomsen's
      disease). In this study, we have electrophysiologically characterized two new
      dominant ClC-1 mutations, thereby elucidating the observed phenotype in patients.
      The two ClC-1 mutants M128V and E193K were identified, and the DNA was isolated
      from patients and subsequently expressed in Xenopus laevis oocytes for
      electrophysiological characterization. Both ClC-1 mutants, M128V and E193K,
      showed a large rightward shift in the current-voltage relationship. In addition,
      the activation kinetics were slowed in the ClC-1 M128V mutant, as compared to the
      wild-type ClC-1. Interestingly, ClC-1 E193K revealed a change in reversal
      potential compared to wild-type channels. This finding supports the notion that
      the E193 amino acid is an important determinant in the selectivity filter of the
      human ClC-1 channel. The electrophysiological behavior of both mutants
      demonstrates a severe reduction in ClC-1 channel conductance under
      physiologically relevant membrane potentials. These studies thereby explain the
      molecular background for the observed myotonia in patients.

PMID- 14639588
TI  - Acute neuropathies after peripheral blood stem cell and bone marrow
      transplantation.
AB  - Neuromuscular complications are not uncommon after bone marrow and stem cell
      transplantation, especially in patients with allogeneic transplantations and
      graft-versus-host disease. The pathogenesis of these complications remains
      unclear, but the changes in immune modulation that occur after transplantation
      are likely to play a key role. We describe 4 patients who developed brachial
      plexopathy (3 cases) or multiple lumbosacral radiculopathies (1 case) between 5
      days and 4 months after autologous peripheral blood stem cell (3 cases) or
      allogeneic bone marrow transplantation without evidence of graft-versus-host
      disease (1 case). Infectious, tumor-related, toxic, and metabolic causes were
      excluded in all cases. Recovery was limited in two cases and nearly complete in
      the other two patients. Brachial plexopathies and polyradiculopathies are
      potential complications of peripheral blood stem cell and bone marrow
      transplantation. It is possible that these disorders may be the result of
      autoimmune phenomena directed against specific nerve antigens.

PMID- 14639589
TI  - Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic
      amyotrophic lateral sclerosis: a hospital-based case-control study.
AB  - We investigated the relationship between the most common 4977-bp deleted
      mitochondrial DNA (mtDNA) mutations and the occurrence of sporadic amyotrophic
      lateral sclerosis (ALS). Primer-shift and quantitative polymerase chain reaction
      (PCR) were used to determine the 4977-bp deleted mtDNA in the muscle specimens
      from 36 patients with sporadic ALS and 69 age-matched controls with other
      neuromuscular disorders. We found that the 4977-bp deleted mtDNA mutations were
      significantly higher in the ALS patients than controls in both frequency (50.0%
      vs. 8.7%, P < 0.01) and amount (0.35 +/- 0.53% vs. 0.085 +/- 0.35%, P < 0.05).
      Subjects with, rather than without, deleted mtDNA were at a significantly higher
      risk for having ALS after adjustment for age and sex. Moreover, male subjects had
      a higher risk than female subjects of having sporadic ALS. This study suggested
      that 4977-bp deleted mtDNA is significantly associated with the occurrence of
      sporadic ALS.

PMID- 14639590
TI  - Endurance training improves skeletal muscle electrical activity in active COPD
      patients.
AB  - The effect of endurance training on muscle electrical activity during general
      exercise testing was investigated in physically active patients with chronic
      obstructive pulmonary disease (COPD). Before and after rehabilitation, patients
      performed identical incremental exercise tests. Pulmonary gas exchange, venous
      lactate and pyruvate concentrations, and the quadriceps electromyographic signal
      were sampled every minute throughout exercise testing. Three weeks of
      rehabilitation increased exercise capacity without modifying pulmonary function.
      M-wave amplitude, root mean square (RMS) of electromyographic activity, and
      RMS/oxygen uptake were increased significantly during post-rehabilitation testing
      at the same exercise intensity compared to pre-rehabilitation. Median frequency
      was significantly lower after training. These modifications reflect greater
      muscle excitability, greater muscle activation for the same level of exercise,
      and higher recruitment of slow-twitch fibers. Pulmonary rehabilitation in active
      COPD patients may normalize the electrical activity of skeletal muscles during
      incremental dynamic exercise. The electromyographic signal confirms neuromuscular
      changes after endurance training.

PMID- 14639591
TI  - Lumbosacral radiculopathy following radiofrequency ablation therapy.
AB  - Radiofrequency ablation (RFA) is a treatment modality for several types of
      malignancies and vascular malformations. Only limited information is available on
      neurologic complications following RFA. We report three cases of acute
      lumbosacral radiculopathy after abdominal RFA, in two of which electrophysiologic
      studies were performed. All three patients had significant spontaneous clinical
      improvement. We suggest the underlying cause was partial axonopathy due to
      thermal injury, but with a good prognosis.

PMID- 14639592
TI  - Late-onset mitochondrial disorder with electromyographic evidence of myotonia.
AB  - We describe a patient with chronic progressive external ophthalmoplegia (CPEO)
      due to a deletion of mitochondrial DNA (mtDNA) who had electromyographic evidence
      of myotonic discharges. Myotonia has not previously been described in association
      with mitochondrial disease and this report extends the known phenotypic
      expression of these disorders.

PMID- 14639593
TI  - Isolated compression of the pectoral nerve resulting in atrophy of the major
      pectoral muscle.
AB  - We report on two cases of isolated damage to a muscle branch of the lateral
      pectoral nerve. Diagnosis was established by the clinical presentation and
      electromyographic examination. In the few reported cases of such injuries, the
      cause was trauma to this region. However, in both of our patients, focal muscle
      atrophy gradually developed after initiation of training schedules to increase
      the cross-section of the major pectoral muscle; we therefore assume that
      compression injury to the nerve by repetitive muscle contractions may be of
      pathogenic relevance. Anatomical studies of this region showed that the nerve
      branches of the lateral pectoral nerve, having to pierce through a connective
      tissue septum that is thicker here by a few millimeters, may be subjected to
      additional risk of compression. Early recognition and treatment are vital to
      prevent associated morbidity of these rare but serious injuries.

PMID- 14639594
TI  - Ocular myasthenia gravis associated with euthyroid ophthalmopathy.
AB  - We report a 71-year-old woman with concomitant ocular myasthenia gravis and
      euthyroid Graves' ophthalmopathy. Unilateral ophthalmoplegia, including ptosis,
      initially was responsive to edrophonium and corticosteroids, except for diplopia
      on upward gaze, but refractory swelling of the inferior rectus muscle and
      proptosis followed. Autoantibodies to acetylcholine and thyrotropin receptors
      were detected. Her ophthalmopathy abated after orbital irradiation in combination
      with systemic steroids. There may be an immunological basis for the association
      of ocular myasthenia gravis with euthyroid Graves' ophthalmopathy.

PMID- 14639595
TI  - Laryngeal electromyography: an evidence-based review.
AB  - This article reports on an evidence-based review of laryngeal electromyography
      (EMG) as a technique for use in the diagnosis, prognosis, and treatment of
      laryngeal movement disorders including the laryngeal dystonias, vocal fold
      paralysis, and other neurolaryngological disorders. The authors performed a
      systematic review of the medical literature from 1944 through 2001 on the
      clinical application of EMG to laryngeal disorders. Thirty-three of the 584
      articles met the predefined inclusion criteria. The evidence demonstrated that in
      a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG
      used to guide injections into the thyroarytenoid muscle in persons with adductor
      spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG
      guided injection and endoscopic injection of botulinum toxin into the posterior
      cricoarytenoid muscle in abductor spasmodic dysphonia found no significant
      difference between the two techniques and no significant treatment benefit. Based
      on the evidence, laryngeal EMG is possibly useful for the injection of botulinum
      toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic
      dysphonia. There were no evidence-based data sufficient to support or refute the
      value of laryngeal EMG for the other uses investigated, although there is
      extensive anecdotal literature suggesting that it is useful for each of them.
      There is an urgent need for evidence-based research addressing the use of
      laryngeal EMG for other applications.

PMID- 14639596
TI  - Isolated musculocutaneous nerve palsy during sleep.

PMID- 14639597
TI  - Absence of mutations in the hypoxia response element of VEGF in ALS.

PMID- 14639599
TI  - The fibroblast: sentinel cell and local immune modulator in tumor tissue.
AB  - Development and progression of epithelial malignancies are frequently accompanied
      by complex phenotypic alterations of resident tissue fibroblasts. Some of these
      changes, such as myofibroblastic differentiation and an oncofetal extracellular
      matrix (ECM) expression profile, are also implicated in inflammation and tissue
      repair. Studies over the past decade revealed the relevance of reciprocal
      interactions between tumor cells and tumor-associated host fibroblasts (TAF) in
      the malignant process. In many tumors, a considerable fraction of the
      inflammatory infiltrate is located within the fibroblast- and ECM-rich stromal
      compartment. However, while fibroblasts are known as "sentinel cells" in various
      nonneoplastic diseases, where they often regulate the composition and function of
      recruited leucocytes, they are hardly considered active participants in the
      inflammatory host response in tumors. This article focuses on the functional
      impact of TAF on immune cells. The complex network of immune-modulating effects
      transduced by TAF and TAF-derived factors is highlighted, and recent reports that
      support the hypothesis that TAF are involved in the inflammatory response and
      immune suppression in tumors are reviewed. The role of TAF-dependent ECM
      remodeling and TAF-derived peptide growth factors, cytokines, and chemokines in
      the immune modulation is stressed and the idea of TAF as an important therapeutic
      target is emphasized.

PMID- 14639600
TI  - NF-kappaB activity blockade impairs the angiogenic potential of human pancreatic
      cancer cells.
AB  - The effect of blockade of NF-kappaB activity on human pancreatic cancer
      angiogenesis was determined in an orthotopic xenograft model. Highly metastatic
      L3.3 human pancreatic cancer cells, which expressed an elevated level of
      constitutive NF-kappaB activity, were transfected with a mutated IkappaBalpha
      (IkappaBalphaM). After implantation in the pancreas of nude mice, parental (L3.3)
      and control vector-transfected (L3.3-Neo) cells produced rapidly growing tumors
      and liver metastases, whereas IkappaBalphaM-transfected (L3.3-IkappaBalphaM)
      cells had decreased tumorigenicity and metastatic potential. NF-kappaB signaling
      blockade significantly inhibited the in vitro and in vivo expression of the major
      proangiogenic molecules vascular endothelial growth factor and interleukin-8 and
      decreased tumor vascular formation. These events were correlated with retarded
      tumor growth and suppression of metastasis. Collectively, these data suggest that
      suppression of tumorigenicity and metastasis by NF-kappaB blockade is due to
      impaired angiogenic potential of tumor cells.

PMID- 14639601
TI  - Suppression of 6A8 alpha-mannosidase gene expression reduced the potentiality of
      growth and metastasis of human nasopharyngeal carcinoma.
AB  - Suppression of alpha-mannosidases by chemicals has been shown to reduce the
      potentiality of growth and metastasis of various tumors. In our study, the effect
      of 6A8 alpha-mannosidase (MAN 6A8), recently discovered in our laboratory, on
      malignant behaviors of tumor cells was examined. Since the suppressive effect of
      chemicals on alpha-mannosidase is not specific, antisense technique was used to
      specifically inhibit expression of the MAN 6A8 in human nasopharyngeal carcinoma
      cells, CNE-2L2. Two cell clones, AS1 and AS2, with pronounced suppression of MAN
      6A8 expression were developed. Wild-type (W), mock-transduced (M) and irrelevant
      DNA-transduced (IR) CNE-2L2 cells with normal expression of the enzyme were used
      as controls. Malignant behaviors of the cells were examined. Significant
      inhibition of growth of AS cells in vitro measured by MTT assay, colony formation
      and anchorage-independent colony formation was found. Pronounced inhibition of
      formation of tumors from AS cells inoculated into nude mice and metastasis was
      also observed. W, M and IR cells cultured in plate wells appeared dispersed with
      a fibroblastic or epithelial morphology, whereas AS cells were in compact sheets
      with an epithelioid organization. Since E-cadherin is the key factor in
      homophilic adhesion of epithelial cells, its expression on the surface of CNE-2L2
      cells was determined. E-cadherin expression on AS cells was enhanced, whereas it
      was markedly diminished on W, M and IR cells. In addition, lamellipodia, which
      play an important role in cell spreading and mobility, almost disappeared on AS
      cells. The results demonstrate a significant suppressive effect of reduced
      expression of MAN 6A8 on malignant behaviors of CNE-2L2 cells.

PMID- 14639602
TI  - p53 polymorphic variants at codon 72 exert different effects on cell cycle
      progression.
AB  - Two common polymorphic forms of the p53 tumor suppressor protein are widely
      distributed throughout the human population. These encode either proline or
      arginine at position 72, and this difference results in a marked alteration in
      the primary structure of the protein. A number of previous studies have shown
      significant differences in the biochemical properties of the p53 protein,
      depending on the particular polymorphic form. There is little information,
      however, on their respective biologic activities. In this study, we have used an
      inducible switch system for expressing both polymorphic forms of p53 within Saos
      2 cells. Cell cycle analysis postinduction of p53 function reveals striking
      differences in how the 2 forms of p53 bring about a cessation of cell growth.
      Thus, the Arg72 form of p53 is significantly more efficient than the Pro72 form
      at inducing apoptosis. In contrast, the Pro72 form appears to induce a higher
      level of G1 arrest than the Arg72 form. These results demonstrate significant
      differences in how the codon 72 polymorphism affects the biological activity of
      p53.

PMID- 14639603
TI  - Rapamycin inhibits cdk4 activation, p 21(WAF1/CIP1) expression and G1-phase
      progression in transformed mouse fibroblasts.
AB  - Rapamycin, a bacterial macrolide antibiotic, is a potent immunosuppressant agent
      that blocks cell proliferation by inhibiting the G1/S transition in several cell
      types. In sensitive cells, rapamycin inhibits the phosphorylation of p70 S6K and
      of Rb; however, the precise mechanisms involved have not been elucidated. In the
      mouse BP-A31 fibroblasts, synchronised in G0/G1 phase by serum starvation and
      induced to reinitiate the G1-phase progression, rapamycin inhibited the entry
      into S phase. The effect of rapamycin was situated in early G1 phase. The
      assembly of the cyclin D1/cdk4 complexes that phosphorylate Rb early in the G1
      phase was not modified by the drug. Nevertheless, an inhibition of the activation
      of cyclin D1/cdk4 and cyclin E/cdk2 as well as of Rb phosphorylation accompanied
      the cell cycle arrest. Remarkably, rapamycin reduced the level of total
      p21(WAF1/CIP1) as well as that of p21(WAF1/CIP1) associated with the cyclin
      D1/cdk4 complexes. Besides its inhibitory activity toward cdk, p21(WAF1/CIP1) has
      been recently found to participate in the formation/stabilisation/nuclear
      translocation of cyclin D1/cdk4 complexes. We propose that the inhibition of the
      expression of p21(WAF1/CIP1) is a mechanism by which rapamycin inhibits the
      triggering of the cdk cascade in the BP-A31 cells.

PMID- 14639604
TI  - nm23-H1 reduces in vitro cell migration and the liver metastatic potential of
      colon cancer cells by regulating myosin light chain phosphorylation.
AB  - The nm23-H1 gene is known as a potential metastasis suppressor gene in various
      types of carcinomas. However, the role of nm23-H1 in colorectal carcinoma still
      remains controversial and the cellular mechanisms by which its protein may
      modulate the metastatic phenotype are not yet known. We transfected nm23-H1 cDNA
      into the human colon cancer cell line, HT-29, to test the effects and cellular
      biological mechanism of nm23 protein in colon cancer. We found that nm23-H1
      strongly inhibited the liver metastasis of HT-29 cells in nude mice and inhibited
      the epidermal growth factor (EGF)-induced cell migration in vitro. Furthermore,
      we clarified the regulation of the myosin light chain (MLC) phosphorylation by
      nm23-H1, which has been demonstrated as having potential role in cell migration.

PMID- 14639605
TI  - Analysis of gene expression profiles in human HL-60 cell exposed to cantharidin
      using cDNA microarray.
AB  - Cantharidin is a natural toxin that has antitumor properties and causes
      leukocytosis as well as increasing sensitivity of tumor cells resistant to other
      chemotherapeutic agents. There is limited information, however, on the molecular
      pharmacological mechanisms of cantharidin on human cancer cells. We have used
      cDNA microarrays to identify gene expression changes in HL-60 promyeloid leukemia
      cells exposed to cantharidin. Cantharidin-treated cells not only decreased
      expression of genes coding for proteins involved in DNA replication (e.g., DNA
      polymerase delta), DNA repair (e.g., FANCG, ERCC), energy metabolism (e.g.,
      isocitrate dehydrogenase alpha, ADP/ATP translocase), but also decreased
      expression of genes coding for proteins that have oncogenic activity (e.g., c
      myc, GTPase) or show tumor-specific expression (e.g., phosphatidylinositol 3
      kinase). In contrast, these treated cells overexpressed several genes that encode
      intracellular and secreted growth-inhibitory proteins (e.g., BTG2, MCP-3) as well
      as proapoptotic genes (e.g., ATL-derived PMA-responsive peptide). Our findings
      suggest that alterations in specific genes functionally related to cell
      proliferation or apoptosis may be responsible for cantharidin-mediated
      cytotoxicity. We also found that exposure of HL-60 cells to cantharidin resulted
      in the decreased expression of multidrug resistance-associated protein genes
      (e.g., ABCA3, MOAT-B), suggesting that cantharidin may be used as an oncotherapy
      sensitizer, and the increased expression of genes in modulating cytokine
      production and inflammatory response (e.g., NFIL-3, N-formylpeptide receptor),
      which may partly explain the stimulating effects on leukocytosis. Our data
      provide new insight into the molecular mechanisms of cantharidin.

PMID- 14639606
TI  - Quantitative real-time RT-PCR for detection of disseminated tumor cells in
      peripheral blood of patients with colorectal cancer using different mRNA markers.
AB  - The detection of disseminated tumor cells in peripheral blood from colorectal
      cancer patients by RT-PCR could be an attractive method for selecting patients
      for adjuvant therapy. We here report on real-time RT-PCR assays (LightCycler) to
      quantitate potential mRNA markers. We investigated specimens from colon carcinoma
      and normal colon mucosa tissues, cell lines, blood samples from 129 patients with
      colorectal cancer (all stages) and 58 reference blood samples (healthy donors,
      persons suffering from inflammatory bowel or infectious diseases). The expression
      profile in tissues showed high values for CEA and CK20, whereas in cell lines
      ProtM was predominant. All markers were detected in reference and patient blood
      samples (ProtM, 22, 17%; CEA, 84, 86%; CK20, 85, 88%). After quantitative
      analysis, the definition of cutoff values for each marker and the combination of
      markers, 13% of patients were judged to have elevated marker concentrations in
      their blood, from which only 6 had values significantly differing from cutoff
      value. There were no differences between stages of disease. In the case of 19
      patients, investigated prior to and 1 week after surgery, 2 samples revealed a
      significant postoperative increase in CEA or CK20 mRNA concentration. In spite of
      high expression levels in tissues and cell lines, we were not able to
      differentiate satisfyingly mRNA markers originating from tumor cells and those
      from illegitimate transcription in hematopoetic cells in blood. We conclude that
      either copy numbers of analyzed markers in circulating tumor cells are not
      sufficient for detection or, more probably, peripheral blood is not a suitable
      compartment for detection of tumor cells in colorectal cancer.

PMID- 14639607
TI  - Frequent somatic mutations of mitochondrial DNA in esophageal squamous cell
      carcinoma.
AB  - Recent studies of various cancers, such as those of the breast, head and neck,
      bladder and lung, reported that 46-64% of somatic mutations in the D-loop region
      of mitochondrial DNA (mtDNA) are observed. However, in esophageal cancer, only a
      low rate (5%) of somatic mutations has so far been reported in one article (Hibi,
      K. et al., Int J Cancer 2001;92:319-321). Thus, to confirm this we analyzed the
      somatic mutations for hypervariable regions (HVR-I and HVR-II) in the D-loop of
      mtDNA to reevaluate the possibility of mitochondrial genetic instability in this
      cancer. We amplified both HVRs by PCR and DNA samples obtained from 38 esophageal
      tumors and matched normal tissues, and then sequenced them. Comparing the
      sequences of tumors to those of normal tissues, we found 14 somatic mutations in
      13 patients (34.2%). Eleven mutations were at the C consecutive stretch from
      position 303 to 309 of MITOMAP in the mitochondria databank
      (http://www.mitomap.org/), 1 at position 215 in HVR-II and 2 at positions 16,304
      and 16,324 in HVR-I. There were 41 types of germ line variations in HVR-I
      including 2 not so far recorded in the mtDNA databank and 17 in HVR-II including
      1 not yet recorded. We also determined nuclear genome instability of these 38
      specimens by analyzing 3 independent microsatellite sequences. While 4 specimens
      showed a single microsatellite change, which is tumor specific, we did not find
      any co-relation between a somatic mtDNA mutation and microsatellite instability
      of nuclear genome DNA. These results suggest that mtDNA mutations might show a
      genetic instability in esophageal cancer independently from a nuclear genome
      instability.

PMID- 14639608
TI  - Short tandem repeat polymorphism in a novel esophageal cancer-related gene
      (ECRG2) implicates susceptibility to esophageal cancer in Chinese population.
AB  - We have previously cloned and identified a novel esophageal cancer related gene 2
      (ECRG2; GenBank Accession Number AF268198), which is down-regulated in esophageal
      squamous cell carcinoma (ESCC) and involved in the induction of the apoptosis in
      esophageal cancer cell lines. In the present study, we have found a short tandem
      repeat (STR) polymorphism in the noncoding region of the exon 4 of the ECRG2 gene
      by using PCR-denaturing high-performance liquid chromatography (DHPLC). Three STR
      genotypes, TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 were revealed and confirmed by DNA
      sequencing analysis. A total of 661 objects including 228 patients with ESCC and
      373 normal controls were analyzed to investigate the impact of this ECRG2 STR
      polymorphism on risk of ESCC in case-control studies. Genotypes were determined
      in 231 controls and 162 cases from Beijing, which is a low risk area of ESCC, and
      in 142 controls and 126 cases from Linxian, a well-known high-risk area of ESCC.
      In both of the Beijing and Linxian population, subjects who carried the TCA3/TCA3
      genotype were at an increased risk of ESCC compared to those carrying the
      TCA4/TCA4 genotype, with the adjusted odds ratios (ORs) being 2.05 [95%
      confidence interval (CI), 1.02-4.06] for the subjects from Beijing and 4.40 (95%
      CI, 1.93-10.01) for the subjects from Linxian. Furthermore, comparison of the
      genotype distributions among other cancer sites might suggest that risk of the
      ECRG2 STR polymorphism might be specific to the esophagus. These findings
      indicate for the first time that the ECRG2 STR is a genetic susceptibility factor
      for ESCC and the TCA3/TCA3 allele might play a role in the development of this
      cancer.

PMID- 14639609
TI  - Mutations of BRAF are associated with extensive hMLH1 promoter methylation in
      sporadic colorectal carcinomas.
AB  - Activating mutations of BRAF have been frequently observed in microsatellite
      unstable (MSI+) colorectal carcinomas (CRCs), in which mutations of BRAF and KRAS
      are mutually exclusive. Previously, we reported that hypermethylation of hMLH1
      might play an important role in the tumorigenesis of right-sided sporadic CRCs
      with MSI showing less frequency of KRAS/TP53 alteration. Therefore, we have
      assumed that BRAF mutations might be highly associated with hMLH1 methylation
      status rather than MSI status. In this study, mutations of BRAF and KRAS and
      their relationship with MSI and hMLH1 methylation status were examined in 140
      resected specimens of CRC. The methylation status was classified into 3 types:
      full methylation (FM), partial methylation (PM) and nonmethylation (NM). Only FM
      closely linked to reduced expression of hMLH1 protein. BRAF mutations were found
      in 16 cases (11%), all leading to the production of BRAF(V599E). As for MSI
      status, BRAF mutations were found in 43% of MSI+ and 4% of MSI- cases (p <
      0.0001). Among the MSI+ individuals, BRAF mutations were more frequent in cases
      with hMLH1 deficiency (58%) than those with hMSH2 deficiency (0%; p=0.02).
      Moreover, they were found in 69% of FM, 4% of PM and 4% of NM, revealing a
      striking difference between FM and the other 2 groups (FM vs. PM or NM; p <
      0.0001). These findings suggest that BRAF activation may participate in the
      carcinogenesis of sporadic CRCs with hMLH1 hypermethylation in the proximal
      colon, independently of KRAS activation.

PMID- 14639610
TI  - Analysis of HLA antigen expression in benign and malignant melanocytic lesions
      reveals that upregulation of HLA-G expression correlates with malignant
      transformation, high inflammatory infiltration and HLA-A1 genotype.
AB  - Previous studies indicate that the nonclassical class I HLA-G antigen, whose
      physiologic expression is mainly restricted to placenta, is upregulated in
      melanoma, renal carcinoma, lung carcinoma, glioblastoma and ovarian carcinoma,
      where its inhibitory effect on cytotoxic effector cells function is thought to
      participate in immune evasion by tumor cells. To define whether this expression
      was a specific feature of melanocytic malignant transformation, 174 paraffin
      embedded melanocytic lesions including naevi, lentigo, primary and metastatic
      melanomas were analyzed for HLA-G and other HLA class I and class II antigen
      expression. HLA-G antigen expression in melanocytic cells was found to be
      significantly higher (p < 0.0003) in melanoma (22/79, 28%) than in naevi (1/70,
      1.4%), suggesting that upregulation of HLA-G is associated with malignant
      transformation in this cell type. Further identification of HLA-G antigen
      expression in inflammatory infiltrating cells results in an overall frequency of
      HLA-G expressing cells that is higher in melanoma (28/79, 35.5%) than in naevi
      (5/60, 8.3%) or lentigo (2/23, 8.7%). Upregulation of HLA-G or HLA class II
      molecules in melanocytic cells thus appears as a better predictor of malignancy
      than classical HLA class I antigen defects, which are often described as an
      important mechanism used by tumor cells to evade immune surveillance.
      Furthermore, HLA-G expression was electively found in lesions that exhibited a
      high inflammatory infiltrate as well as in patients displaying HLA-A1 genotype.
      These findings may provide new insights in the comprehension of tumor progression
      and design of therapeutic approaches aimed at enhancing antitumor immune
      responses in melanoma patients.

PMID- 14639611
TI  - Synergy between anti-endoglin (CD105) monoclonal antibodies and TGF-beta in
      suppression of growth of human endothelial cells.
AB  - Endoglin (CD105) is a proliferation-associated cell membrane antigen of
      endothelial cells and strongly expressed in the angiogenic vasculature of solid
      tumors. Endoglin is essential for angiogenesis/vascular development and an
      ancillary transforming growth factor beta (TGF-beta) receptor. Certain anti
      endoglin monoclonal antibodies (mAbs), termed SN6 series mAbs, inhibited
      angiogenesis, tumor growth and metastasis in mice. We investigated the mechanisms
      by which anti-endoglin mAbs suppress growth of proliferating endothelial cells.
      We found that 4 SN6 series mAbs suppressed growth of human umbilical vein
      endothelial cells (HUVECs) in a dose-dependent manner in the absence of any
      effector cells or complement. Significant differences in the growth suppression
      between the 4 anti-endoglin mAbs defining different epitopes were observed. These
      differences were not determined by antigen-binding avidities of the mAbs.
      Combination of TGF-beta1 and each of the 4 anti-endoglin mAbs exerted synergistic
      growth suppression of HUVECs. Binding of anti-endoglin mAbs to endoglin
      expressing cells did not block the subsequent binding of TGF-beta1. Conversely,
      preincubation of HUVECs with TGF-beta1 did not change cell surface expression of
      endoglin. The present results suggest that direct suppression of the endothelial
      cell growth by SN6 series mAbs is one of the underlying mechanisms by which anti
      endoglin mAbs exert antiangiogenic and tumor-suppressive activity in vivo. The
      results further suggest that TGF-beta1 plays an important role in the in vivo
      antiangiogenic efficacy of anti-endoglin mAbs by synergistically enhancing the
      activity of these mAbs. Further studies of the present novel findings may provide
      valuable information about the functional roles of endoglin and anti-endoglin
      mAbs in the TGF-beta-mediated cell regulation.

PMID- 14639612
TI  - Can cervical cancer screening be stopped at 50? The prevalence of HPV in elderly
      women.
AB  - Although the relation between cervical cancer and the human papillomavirus (HPV)
      has been established beyond doubt, the introduction of HPV detection in cervical
      cancer screening is halted, primarily by the high rate of false positivity in
      relation to morbidity, since the majority of women infected with HPV will not
      develop lesions. To counteract overconsumption of cervical cancer screening in
      elderly women, we wanted to test the hypothesis that women of 50 years or older
      who are HPV-negative and have a cytologically normal smear might be encouraged to
      refrain from further screening. As a first step, the prevalence of high-risk HPV
      in a population of 1,936 women of 50 years and older was investigated. After an
      initial decline, a slightly higher prevalence can be seen with increasing age.
      There is a decrease in the prevalence of multiple infections with age, paralleled
      by an increase in single infections, especially of HPV type 16 in the eldest-age
      group. However, neither the decrease in multiple infections nor the increase in
      single infections is statistically significant. The data obtained in this study
      show that, even in the presence of a slight increase in the HPV prevalence in
      elderly women, approximately 94% of the elderly women can be withdrawn from the
      cervical cancer screening. However, a follow-up study will be necessary to
      determine the frequency of (re)infection as well as the course of an HPV
      infection in elderly women.

PMID- 14639613
TI  - Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of
      endometrial cancer.
AB  - Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin
      dependent diabetes mellitus and polycystic ovary syndrome, are associated with an
      increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels
      of IGF-binding proteins have been shown to be associated with increased risk of
      several cancer types that are frequent in affluent societies. We investigated for
      the first time in a prospective study the association of pre-diagnostic blood
      concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I,
      IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested
      within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). It included
      166 women with primary invasive endometrial cancer and 315 matched controls, of
      which 44 case and 78 control subjects were premenopausal at recruitment.
      Endometrial cancer risk increased with increasing levels of C-peptide (ptrend =
      0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91
      11.8] for the highest quintile. This association remained after adjustment for
      BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1
      levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the
      upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost
      statistical significance after adjustment for confounders [ptrend = 0.06; OR in
      the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I,
      IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased
      circulating C-peptide, is associated with increased endometrial cancer risk.
      Decrease in the prevalence of chronic hyperinsulinemia, through changes in
      lifestyle or medication, is expected to prevent endometrial cancer.

PMID- 14639614
TI  - Fruits and vegetables and lung cancer: Findings from the European Prospective
      Investigation into Cancer and Nutrition.
AB  - Intake of fruits and vegetables is thought to protect against the development of
      lung cancer. However, some recent cohort and case-control studies have shown no
      protective effect. We have assessed the relation between fruit and vegetable
      intake and lung cancer incidence in the large prospective investigation on diet
      and cancer, the European Prospective Investigation Into Cancer and Nutrition
      (EPIC). We studied data from 478,021 individuals that took part in the EPIC
      study, who were recruited from 10 European countries and who completed a dietary
      questionnaire during 1992-1998. Follow-up was to December 1998 or 1999, but for
      some centres with active follow-up to June 2002. During follow-up, 1,074
      participants were reported to have developed lung cancer, of whom 860 were
      eligible for our analysis. We used the Cox proportional hazard model to determine
      the effect of fruit and vegetable intake on the incidence of lung cancer. We paid
      particular attention to adjustment for smoking. Relative risk estimates were
      obtained using fruit and vegetable intake categorised by sex-specific, cohort
      wide quintiles. After adjustment for age, smoking, height, weight and gender,
      there was a significant inverse association between fruit consumption and lung
      cancer risk: the hazard ratio for the highest quintile of consumption relative to
      the lowest being 0.60 (95% Confidence Interval 0.46-0.78), p for trend 0.0099.
      The association was strongest in the Northern Europe centres, and among current
      smokers at baseline, and was strengthened when the 293 lung cancers diagnosed in
      the first 2 years of follow-up were excluded from the analysis. There was no
      association between vegetable consumption or vegetable subtypes and lung cancer
      risk. The findings from this analysis can be regarded as re-enforcing
      recommendations with regard to enhanced fruit consumption for populations.
      However, the effect is likely to be small compared to smoking cessation.

PMID- 14639615
TI  - Serum enterolactone concentration is not associated with breast cancer risk in a
      nested case-control study.
AB  - The lignan enterolactone produced by the intestinal microflora from dietary
      precursors has been hypothesized to protect against hormone-dependent cancers. We
      conducted a nested case-control study to examine the relationship between serum
      enterolactone concentration and risk of breast cancer. Enterolactone
      concentrations were measured by time-resolved fluoroimmunoassay in serum
      collected at 4 independent cross-sectional population surveys from 206 women with
      breast cancer diagnosed during follow-up (mean 8.0 years) and from 215 controls
      frequency-matched to cases by study cohort, 5-year age group and study area. Mean
      serum enterolactone concentration (nmol/l) did not significantly differ between
      case and control subjects [25.2 (SD 22.2) vs. 24.0 (SD 21.3), respectively]. Odds
      ratios for breast cancer risk estimated by conditional logistic regression for
      increasing concentration of enterolactone in quartiles were 1.00 (referent), 1.67
      (95% CI 0.95-2.95), 1.71 (95% CI 0.96-3.06) and 1.30 (95% CI 0.73-2.31), and p
      for trend was 0.48. Our findings do not support the hypothesis that high serum
      enterolactone concentration is associated with reduced risk of breast cancer.

PMID- 14639616
TI  - Medication use and risk of ovarian carcinoma: a prospective study.
AB  - Inflammation and gonadotropins are hypothesized to influence ovarian
      carcinogenesis. In a prospective study, we evaluated ovarian cancer risk
      associated with self-reported use of medications that influence inflammation or
      gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up
      Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed
      questionnaires through 1998 to update risk factor information and identify
      incident ovarian cancers. The 1992-95 questionnaire ascertained medication use,
      including duration and frequency of use for aspirin, acetaminophen, other
      nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine
      receptor antagonists. A Poisson regression analysis generated rate ratios (RRs)
      and 95% confidence intervals (CIs) for the 31,364 women who were at risk of
      ovarian cancer and responded to the questionnaire that queried regular medication
      use. One hundred sixteen women developed ovarian cancer during follow-up. None of
      the anti-inflammatory medications was associated with ovarian cancer, but the RR
      for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5)
      and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI
      0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but
      histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6,
      95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to
      increase risk. In our study, neither anti-inflammatory medications nor anti
      psychotic medications were associated with ovarian cancer. Potential associations
      with histamine-receptor antagonists may warrant further study.

PMID- 14639617
TI  - Fat, fiber, fruits, vegetables, and risk of colorectal adenomas.
AB  - A case-control study was conducted at the National Naval Medical Center
      (Maryland, USA) from 1994 to 1996 to investigate the possible association between
      dietary factors and colorectal adenomas. Cases (n = 239) were subjects diagnosed
      with adenomas (146 new and 93 recurrent) by sigmoidoscopy or colonoscopy. Those
      with no evidence of adenomas found by sigmoidoscopy were recruited as controls (n
      = 228). Dietary variables, assessed by a 100-item food frequency questionnaire,
      were analyzed by the logistic regression model, which was adjusted for age,
      gender and total energy intake. Variables of fat intake were further adjusted for
      red meat intake. An increased risk of 7% [odds ratio (OR): 1.07; 95% confidence
      interval (95% CI): 0.94-1.22] per 5% energy/day from total fat was observed.
      Every additional 5% unit of oleic acid intake/day significantly increased the
      adenoma risk by 115% (OR: 2.15; 95% CI: 1.05-4.39). Red meat fat increased the
      risk by 20% (OR: 1.20; 95% CI: 0.71-2.04), and white meat fat decreased the risk
      by 67% (OR: 0.33; 95% CI: 0.19-0.95) for every additional 5% unit of respective
      intake/day. Risk decreased by 41% (OR: 0.59; 95% CI: 0.41-0.86) for every
      additional 5% unit of fiber intake/day. Vegetable [OR per 100 g of vegetable
      intake/day: 0.83, 95% CI: 0.67-1.04] and fruit (OR per 100 g of fruit intake/day:
      0.92, 95% CI: 0.82-1.03) intake showed an inverse association, and the results
      are suggestive of an association with the risk for adenomas. In conclusion, a
      strong positive association between oleic acid intake and colorectal adenoma risk
      was observed. This is likely to be an indicator of "unhealthy" food (meat, dairy,
      margarine, mayonnaise, sweet baked food) consumption in this population.
      Increased intake of dietary fiber was associated with a moderately decreased risk
      of adenomas.

PMID- 14639618
TI  - An in vitro model to optimize dose scheduling of multimodal radioimmunotherapy
      and chemotherapy: effects of p53 expression.
AB  - Several reports have appeared on the use of combined radioimmunotherapy (RAIT)
      and chemotherapy. The choice of drug to use with RAIT and how to space the two
      treatments has not been completely addressed. Because every patient's cancer
      presents with a specific molecular phenotype, we hypothesized that it may be
      necessary to tailor therapy based on specific gene expression. We addressed how
      the form of expression of a single gene, the p53 tumor suppressor, would impact
      the choice of agents, as well as sequence and spacing of agents. p53 regulates
      cell cycle arrest to allow for DNA repair after therapy-induced small DNA damage
      or induction of apoptosis if damage is great and has been shown to affect chemo-
      and radiosensitivity of cancer cells. We established 3 stable p53 transfectants
      of the SKOV-3 p53null parental line (p53(wt), p53(143mut) or p53(273mut)). p53
      expression was confirmed using flow cytometry, using the DO1 pan-p53 Ab and the
      PAb240 anti-p53mut Ab. The colorimetric MTT assay was then used to measure dose
      dependent growth inhibition from single modality chemotherapy (doxorubicin,
      carboplatin, paclitaxel or topotecan) or radioimmunotherapy (90Y-RS-7 IgG anti
      EGP1). The % survival vs. log [drug] were plotted to obtain the IC50. We then
      used a matrix design in which we varied the sequence of the first and second
      modality of treatment and the spacing between the 2 treatments to determine the
      most synergistic and antagonistic combinations for the parental SKOV-3 and each
      of the 3 transfectants. The IC50 for each therapeutic agent varied as a function
      of the form of p53 expressed. For example, of the 4 lines, the p53wt transfectant
      was the most resistant to topotecan and the 143mut was the most resistant to
      carboplatin. The 273mut was quite sensitive to both doxorubicin and paclitaxel,
      whereas the p53null and wt were not. For multimodal treatments, most combinations
      of RAIT and chemotherapy resulted in a 30-40% growth inhibition (GI) and were
      either additive or moderately antagonistic. The 3 best (>60% GI) and 3 worst
      (<25% GI) combinations were identified and were unique to the parental p53null
      and to the 3 transfectants. Certain combinations showed clear synergy and others
      were antagonistic, with the first treatment modality blocking the growth
      inhibitory effects of the second treatment modality. The form of p53 expressed
      affects chemosensitivity and radiosensitivity and will influence optimal
      multimodal therapy with RAIT and chemotherapy and the dose-schedule (sequential
      with RAIT first or with drug first) when more than 1 agent is used.

PMID- 14639619
TI  - Anti-neovascular therapy by liposomal drug targeted to membrane type-1 matrix
      metalloproteinase.
AB  - Because membrane type-1 matrix metalloproteinase (MT1-MMP) is expressed
      specifically on the angiogenic endothelium as well as tumor cells, an agent
      possessing the ability to bind to this molecule might be useful as a tool for
      active targeting of tumor angiogenic vessels. Based on the sequences of peptide
      substrates of MT1-MMP, which had been determined by using a phage-displayed
      peptide library, we examined the binding ability of peptide-modified liposomes
      for endothelial cells and targeting ability for tumor tissues by positron
      emission tomography (PET). Liposomes modified with stearoyl-Gly-Pro-Leu-Pro-Leu
      Arg (GPLPLR-Lip) showed high binding ability to human umbilical vein endothelial
      cells and accumulated in the tumor about 4-fold more than did the unmodified
      liposomes. Because we reported previously that liposomalized 5'-O
      dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino
      pentofuranosylcytosine (DPP-CNDAC), a hydrophobized derivative of the novel
      antitumor nucleoside CNDAC, strongly suppressed tumor growth when delivered in
      liposomes modified with another angiogenic homing peptide, we examined the
      antitumor activity of DPP-CNDAC entrapped in GPLPLR-Lip. DPP-CNDAC/GPLPLR-Lip
      showed significant tumor growth suppression compared to DPP-CNDAC/unmodified
      liposomes. These results suggest that DPP-CNDAC-liposomes modified with MT1-MMP
      targeted peptide are useful for cancer anti-neovascular therapy (ANET), namely,
      tumor growth suppression by damage to angiogenic endothelial cells.

PMID- 14639620
TI  - Humoral immune response against melanoma antigens induced by vaccination with
      cytokine gene-modified autologous tumor cells.
AB  - Although the existence of a humoral response against tumor-associated antigens is
      well appreciated, a systematic analysis of its possible induction by the tumor
      remains missing. We compared the specific IgG response of Stage IV melanoma
      patients during vaccination. Patients had been treated within 2 clinical trials
      with autologous tumor cells gene-modified for IL-7 or IL-12. A panel of 27 tumor
      associated antigens (HD-MM-01 to HD-MM-27) was isolated by a SEREX screening of a
      testis cDNA library using a pool of 5 sera from patients after vaccination. All
      antigens were retested with individual sera of 12 patients both pre- and post
      vaccination. A serological response was induced during vaccination against 18
      antigens. Remarkably, induction was detected only in patients included in the
      screening pool. The low overlap between sero-reactivity of the 12 patients
      suggested a very individualized immunological reaction. Two of 5 sera included in
      the screening pool exhibited a high frequency of induced humoral responses. The
      same patients had been shown to have a high Karnovsky index and had generated
      lytic cytotoxic T cells against the tumor. Besides 2 known cancer-germline genes
      (SCP-1 and PLU-1), the other isolated antigens were expressed in a non-tumor
      specific fashion as analyzed by virtual Northern blot or RT-PCR. The properties
      of homologues to several of the identified tumor-antigens, especially PLU-1, SCP
      1, DNEL2, CLOCK, and PIASx-alpha, suggest further investigation of their possible
      function in malignant melanoma. We conclude that a strong humoral response
      against tumor-associated antigens is inducible by tumor cells and that this
      response is very individual.

PMID- 14639621
TI  - Expression of PAX 3 alternatively spliced transcripts and identification of two
      new isoforms in human tumors of neural crest origin.
AB  - The developmental gene PAX 3 is expressed in the early embryo in developing
      muscle and elements of the nervous system, including the brain. Since no one has
      investigated the expression of the isoforms of PAX 3 in the neuroectodermal
      tumors melanoma and small cell lung cancer (SCLC), we have carried out a
      comprehensive screening for the expression of the isoforms PAX 3a-e using RT-PCR
      in human melanoma cell lines, primary human ocular and secondary cutaneous
      melanomas. We have identified 2 new isoforms of PAX 3, g and h, which we have
      isolated, cloned and sequenced. Sets of primers for each isoform were designed
      and their specificity was confirmed by sequence analysis of the products. The
      isoforms PAX 3a-e were detected in all human cutaneous melanoma cell lines (8/8),
      but only PAX 3c (1/2) and PAX 3d (2/2) in ocular melanoma cell lines. The same
      PAX 3 isoforms were detected in more than 80% of human cutaneous melanomas: PAX
      3a and b (15/17), PAX 3c (14/17), PAX 3d (16/17) and PAX 3e (15/17). In contrast
      the results for 7 SCLC cell lines were PAX 3a (0/7), PAX 3b (1/7), PAX 3c (3/7),
      PAX 3d (6/7), PAX 3e (2/7); 8/8 cutaneous melanoma cell lines and 8/8 ocular
      melanoma tissues, together with 14/17 cutaneous melanoma tissues screened,
      expressed the new isoform PAX 3g. All 8 cutaneous melanoma cell lines expressed
      PAX 3h, but it was not detectable in any of the tumor tissues (0/20). Neither of
      the 2 ocular melanoma cell lines expressed the 2 new isoforms. Comparison of the
      different amplicon staining intensities on a gel suggests that PAX 3c and PAX 3d
      are the predominant transcripts expressed, with relatively low expression of PAX
      3e and PAX 3h. We propose that these and the 2 new isoforms we have discovered
      may be important in oncogenesis and differential diagnosis of melanomas or SCLC.

PMID- 14639623
TI  - Thymoma and subsequent cancers.

PMID- 14639622
TI  - Beta-catenin activates a coordinated expression of the proinvasive factors
      laminin-5 gamma2 chain and MT1-MMP in colorectal carcinomas.
AB  - In colorectal carcinomas, loss-of-function mutations of the adenomatous polyposis
      coli (APC) tumor suppressor gene lead to a nuclear accumulation of the oncogenic
      transcriptional activator beta-catenin, predominantly at the invasive front
      within the tumor host interface. Various identified genes activated by beta
      catenin are associated with tumor invasion. One prerequisite for malignant tumor
      invasion is the ability of tumor cells to migrate. We recently described the
      gamma2 chain of laminin as another beta-catenin target gene. Fragments of the
      laminin gamma2 chain, resulting from cleavage by the membrane type 1 matrix
      metalloproteinase (MT1-MMP), are strong inducers of epithelial cell migration. We
      here show a coordinated expression of nuclear beta-catenin, its target gene and
      MT1-MMP substrate laminin gamma2 chain, as well as MT1-MMP in tumor cells at
      invasive regions of colorectal carcinomas. We further demonstrate that MT1-MMP
      expression is regulated by beta-catenin/TCF through a TCF binding site in its
      promoter. These results suggest that nuclear beta-catenin activates the
      coordinated expression of the interacting proinvasive proteins laminin gamma2
      chain and MT1-MMP, thereby leading to a promigratory activity at the invasive
      front of colorectal cancers. This further supports an important role of beta
      catenin for invasion and metastasis of colorectal carcinomas.

PMID- 14639627
TI  - Shape-persistency and molecular function in heteromacrocycles: creation of
      heteroarenecyclynes and arene-azaarenecyclynes.
AB  - On the basis of our concept that the introduction of heteroatoms and shape
      persistency into the pi-macrocycles should bring forth striking functions or
      properties, heteroarenecyclynes (such as oxaarenecyclynes and thiaarenecyclynes)
      with semi-shape-persistent structure, and arene-azaarenecyclynes with shape
      persistent structure have been prepared. Their novel functions and characteristic
      properties are disclosed. Noteworthy is that heteroarenecyclynes include C(60) to
      provide a Saturn-type complex with a N(2) binding function. A simple member of
      the oxaarenecyclyne compounds undergoes the Ag(I)-induced cyclization leading to
      the quantitative formation of strongly luminescent perylene derivative. Arene
      azaarenecyclynes are versatile compounds. For example, they exhibit intense
      luminescence in spite of the meta-bonding structure, providing the circular
      luminophore. Also they serve as receptors for special metal, organic, and
      inorganic substrates. The observed molecular functions are valuable for
      scientific and practical application.

PMID- 14639628
TI  - From rare gas atoms to fullerenes: spherical aromaticity studied from the point
      of view of atomic structure theory.
AB  - The characteristic features of molecules like polyhedra and fullerenes, which
      follow the 2(N+1)(2) rule of spherical aromaticity, can be related to
      energetically stable closed-shell configurations of (pseudo-)atoms. This unifying
      view relies on a thought experiment, which produces a polyhedron in a two-step
      process and which can, in turn, relate the electronic configuration of any
      spherical polyhedron to the one of a corresponding closed-shell atom. In the
      first step, the electronic ground-state configuration is identified. In the
      second step, a group theoretical analysis can be carried out; this relates the
      spherically symmetric atomic orbitals to the molecular orbitals classified
      according to the irreducible representations of the point group of the polyhedron
      under consideration. This procedure explains and justifies the pseudo-l
      classification of molecular orbitals, which is the basis of the 2(N+1)(2) rule.
      For the transition from the electronic configuration of the rare gas Eka-Rn (Uuo)
      to the icosahedral fullerene C(20) (2+), we show how a change in the ground-state
      configuration leads to the phenomenologically found 2(N+1)(2) rule for
      spherically aromatic fullerenes.

PMID- 14639629
TI  - Towards binuclear polyaminocarboxylate MRI contrast agents? Spectroscopic and MD
      study of the peculiar aqueous behavior of the LnIII chelates of OHEC (Ln=Eu, Gd,
      and Tb): implications for relaxivity.
AB  - We report the study of binuclear Ln(III) chelates of OHEC
      (OHEC=octaazacyclohexacosane-1,4,7,10,14,17,20,23-octaacetate). The
      interconversion between two isomeric forms, which occurs in aqueous solution, has
      been studied by NMR, UV/Vis, EPR, and luminescence spectroscopy, as well as by
      classical molecular dynamics (MD) simulations. For the first time we have
      characterized an isomerization equilibrium for a Ln(III) polyaminocarboxylate
      complex (Ln(III)=Y, Eu, Gd and Tb) in which the metal centre changes its
      coordination number from nine to eight, such that: [Ln(2)(ohec)(H(2)O)(2)](2-)
      r<==>[Ln(2)(ohec)](2-)+2 H(2)O. The variable temperature and pressure NMR
      measurements conducted on this isomerization reaction give the following
      thermodynamic parameters for Eu(III): K(298)=0.42+/-0.01, DeltaH(0)=+4.0+/-0.2 kJ
      mol(-1), DeltaS(0)=+6.1+/-0.5 J K(-1) mol(-1) and DeltaV(0)=+3.2+/-0.2 cm(3) mol(
      1). The isomerization is slow and the corresponding kinetic parameters obtained
      by NMR spectroscopy are: k(298)(is)=73.0+/-0.5 s(-1), DeltaH++(is)=75.3+/-1.9 kJ
      mol(-1), DeltaS++(is)= +43.1+/-5.8 J K(-1) mol(-1) and DeltaV++(is)=+7.9+/-0.7
      cm(3) mol(-1). Variable temperature and pressure (17)O NMR studies have shown
      that water exchange in [Gd(2)(ohec)(H(2)O)(2)](2-) is slow, k(298)(ex)=(0.40+/
      0.02)x10(6) s(-1), and that it proceeds through a dissociative interchange I(d)
      mechanism, DeltaV( not equal )=+7.3+/-0.3 cm(3) mol(-1). The anisotropy of this
      oblong binuclear complex has been highlighted by MD simulation calculations of
      different rotational correlation times. The rotational correlation time directed
      on the Gd-Gd axis is 24 % longer than those based on the axes orthogonal to the
      Gd-Gd axis. The relaxivity of this binuclear complex has been found to be low,
      since 1) only [Gd(2)(ohec)(H(2)O)(2)](2-), which constitutes 70 % of the
      binuclear complex, contributes to the inner-sphere relaxivity and 2) the
      anisotropy of the complex prevents water molecules from having complete access to
      both Gd(III) cages; this decreases the outer-sphere relaxivity. Moreover, EPR
      measurements for the Gd(III) and for the mixed Gd(III)/Y(III) binuclear complexes
      have clearly shown that the two Gd(III) centres interact intramolecularly; this
      enhances the electronic relaxation of the Gd(III) electron spins.

PMID- 14639630
TI  - MD simulations of acyclic and macrocyclic Gd3+-based MRI contrast agents:
      influence of the internal mobility on water proton relaxivity.
AB  - Classical molecular dynamics simulations with a force field adapted to the family
      of Gd(3+) polyaminocarboxylate complexes have been successfully applied on two
      macrocyclic ([Gd(DOTA)(H(2)O)](-) and [Gd(DO3A)(H(2)O)(2)]) and two acyclic
      ([Gd(DTPA)(H(2)O)](2-) and [Gd(EGTA)(H(2)O)](-)) complexes in aqueous solution
      (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane, DO3A=1,4,6
      tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane, DTPA=1,1,4,7,7
      pentakis(carboxymethyl)-1,4,7-triazaheptane, EGTA=1,1,10,10
      tetrakis(carboxymethyl)-1,10-diaza-4,7-dioxadecane). In both macrocylic complexes
      the Gd(3+) coordination polyhedron remains close to a monocapped square antiprism
      (MSA) during the entire simulation time. For the stereolabile acyclic complexes
      different interconverting sets of geometries are observed: three sets close to
      tricapped trigonal prisms (TTP) for [Gd(EGTA)(H(2)O)](-) and three sets
      intermediate between MSA and TTP (distorted C(2v) symmetry) for
      [Gd(DTPA)(H(2)O)](2-). The fast conformational changes observed in the acyclic
      complexes might weaken the hydration of the second water shell and therefore
      disfavour the outer-sphere relaxivity. Moreover, the motions of the chelate
      observed in both acyclic complexes involve the reorientation of the symmetry
      elements over time. This reorientation, occurring on a picosecond timescale, can
      be associated with the correlation time for modulation of the zero field
      splitting and might participate in the electron spin relaxation mechanisms of the
      Gd(3+) ion. The internal motion of the inner-sphere water molecule can be
      quantified by the ratio tau(R)(GD-HW)/tau(R)(GD-OW) which increases slightly from
      0.7 for the acyclic to 0.8 for the macrocyclic complexes. This increase for the
      macrocylic chelates is favourable for a higher relaxivity and can be related to
      their rigidity. The water exchange rate on the four complexes has been related to
      the steric constraint of the ligand on the inner-sphere water molecule(s), which
      is inversely proportional to a geometrical descriptor, the solid angle psi. A
      range of psi values is given (2<<psi<3.3) where the exchange should be optimal.
      The observations made on the picosecond timescale give general directions for the
      design of more efficient magnetic resonance imaging contrast agents.

PMID- 14639631
TI  - Preparation and properties of centrally bridgehead-substituted
      hexacyclo[4.4.0.02,1.03,5.04,8.07,9]decanes ("diademanes") and related (CH)10
      hydrocarbons.
AB  - 6-Trimethylsilyl- (1 b), 6-hydroxymethyl- (1 e), and 6-methyldiademane (1 f) have
      been prepared by irradiation of the corresponding snoutene derivatives, in 23,
      2.8, and 17 % yields, respectively, together with the isomeric 1-trimethylsilyl-
      (10 b) and 1-methyldiademane (10 f) (8 and 2 % yields, respectively). The
      starting 4-trimethylsilyl- (9 b) and 4-(trimethylsilyloxymethyl)snoutene (9 d)
      were prepared from the correspondingly substituted cyclooctatetraenes 4 b and 4 c
      in several steps in 20 and 8 % overall yields, respectively. Upon heating, as
      well as under the conditions of gas-chromatographic separation, diademanes 1 b,
      10 b, 1 f, and 10 f rearranged into the corresponding C10- and C1-substituted
      triquinacenes 3 b, 3 f, 11 b, and 11 f, respectively. Rough kinetic measurements
      of these rearrangements indicate some acceleration of the reaction caused by the
      presence of a methyl substituent and retardation by that of a trimethylsilyl
      substituent, relative to the parent diademane 1 a. At this insufficient
      precision, however, the activation energies (E(a)) of 29.0 and 28.1 kcal mol(-1),
      respectively, are essentially the same as that reported for 1 a (28.3 kcal mol(
      1)). An X-ray crystal structure analysis of trimethylsilylsnoutene 9 b revealed a
      significant lengthening of the distal (with respect to the substituent) bond
      (1.534 versus 1.505 A) in the unsubstituted cyclopropane ring. In the substituted
      cyclopropane ring, the two proximal bonds are lengthened (1.530 A) and the distal
      bond is slightly shortened 1.492 A). This indicates a small, but significant
      electron-withdrawing effect of the trimethylsilyl group in 9 b. An X-ray crystal
      structure analysis of 6-hydroxymethyldiademane 1 e showed pronounced alternation
      of the bond lengths in the six-membered ring, with 1.494(4) between and 1.539(4)
      A within the three cyclopropane moieties, in close agreement with computations at
      different theoretical levels. This structural feature corroborates a
      predisposition of the tris-sigma-homobenzene skeleton of this molecule in the
      ground state to undergo the facile [sigma(2)(s) + sigma(2)(s) + sigma(2)(s)]
      cycloreversion to the triquinacene skeleton observed for the parent diademane 1
      a, its derivative 1 b and 1 f, as well as for other tris-sigma-homobenzene
      derivatives.

PMID- 14639632
TI  - Studies towards simalikalactone D and quassimarin: construction of an advanced
      pentacyclic intermediate.
AB  - An advanced pentacyclic intermediate, amenable to further elaboration into the
      target molecules simalikalactone D and quassimarin, has been synthesized from (S)
      (+)-carvone in 21 steps and with an overall yield of 12 %. The synthesis is
      efficient, stereocontrolled, enantiospecific, and chirality productive, creating
      eight new chiral centres in pentacycle, and should provide opportunities for
      rapid access to simalikalactone D analogues and other bioactive quassinoids. The
      reaction sequence involves a regioselective bishydroxylmethylation, a
      stereocontrolled epoxidation, an epoxymethano-bridge formation, a 1,3-sigmatropic
      rearrangement and an intramolecular Diels-Alder reaction as the key steps.

PMID- 14639633
TI  - Gas-phase detection of HSOH: synthesis by flash vacuum pyrolysis of di-tert-butyl
      sulfoxide and rotational-torsional spectrum.
AB  - Gas-phase oxadisulfane (HSOH), the missing link between the well-known molecules
      hydrogen peroxide (HOOH) and disulfane (HSSH), was synthesized by flash vacuum
      pyrolysis of di-tert-butyl sulfoxide. Using mass spectrometry, the pyrolysis
      conditions have been optimized towards formation of HSOH. Microwave spectroscopic
      investigation of the pyrolysis products allowed-assisted by high-level quantum
      chemical calculations--the first measurement of the rotational-torsional spectrum
      of HSOH. In total, we have measured approximately 600 lines of the rotational
      torsional spectrum in the frequency range from 64 GHz to 1.9 THz and assigned
      some 470 of these to the rotational-torsional spectrum of HSOH in its ground
      torsional state. Some 120 out of the 600 lines arise from the isotopomer
      H(34)SOH. The HSOH molecule displays strong c-type and somewhat weaker b-type
      transitions, indicating a nonplanar skew chain structure, similar to the
      analogous molecules HOOH and HSSH. The rotational constants (MHz) of the main
      isotopomer (A=202 069, B=15 282, C=14 840), determined by applying a least
      squares analysis to the presently available data set, are in excellent agreement
      with those predicted by quantum-chemical calculations (A=202 136, B=15 279, C=14
      840). Our theoretical treatment also derived the following barrier heights
      against internal rotation in HSOH (when in the cis and trans configurations) to
      be V(cis) approximately equal to 2216 cm(-1) and V(trans) approximately equal to
      1579 cm(-1). The internal rotational motion results in detectable torsional
      splittings that are dependent on the angular momentum quantum numbers J and K(a).

PMID- 14639634
TI  - Azolylpentazoles as high-energy materials: a computational study.
AB  - The structures of highly energetic substituted pentazole compounds and their
      decomposition to give dinitrogen and the corresponding azide were investigated by
      ab initio quantum chemical methods. The substituents include azolyl groups (five
      membered aromatic rings with different numbers of nitrogen atoms), CH(3), CN, and
      F. The decomposition pathway was followed for several substituted azolyl- and
      phenylpentazoles and compared to the known experimental and theoretical results.
      The NMR parameters of most of the as-yet unknown pentazole compounds were
      predicted. The activation energy for the decomposition increases, while the
      decomposition energy of the substituted pentazole decreases with greater electron
      donating character of the substituent of the pentazole. Thus, anionic pentazoles
      are more stable than neutral pentazoles. Methylpentazole is predicted to be among
      the most stable pentazoles, even though it does not contain an aromatic system.

PMID- 14639635
TI  - Terpenoids with a new skeleton and novel triterpenoids with anti-inflammatory
      effects from Garcinia subelliptica.
AB  - Three novel phloroglucinol derivatives, garcinielliptones F (1), H (3), and I
      (4), and two novel terpenoids, garcinielliptones G (2) and J (5), with a new
      skeleton have been isolated from the seeds of Garcinia subelliptica. Their
      structures, including relative configurations, were elucidated by spectroscopic
      methods and computer-generated molecular modeling. Compound 1 showed potent
      inhibitory effects on the release of beta-glucuronidase and lysozyme from rat
      neutrophils that had been stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin
      B (CB). This effect was concentration-dependent with IC(50) values of 26.9+/-2.6
      and 20.0+/-1.3 microM, respectively. Compound 1 also showed a potent
      concentration-dependent inhibitory effect on superoxide anion generation in rat
      neutrophils stimulated with fMLP/CB, with an IC(50) value of 17.0+/-0.9 microM.
      Compound 4 showed a potent inhibitory effect on NO production in culture media of
      N9 cells in response to lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) in
      a concentration-dependent manner with an IC(50) value of 7.4+/-0.2 microM.

PMID- 14639636
TI  - Electron density investigation of a push-pull ethylene (C14H24N2O2.H2O) by X-ray
      diffraction at T = 21 K.
AB  - The electron charge distribution in a strongly twisted push-pull ethylene [PPE, 3
      (1,3-diisopropyl-2-imidazolidinylidene)-2,4-pentanedione] has been determined by
      low temperature (T = 21 K) single-crystal X-ray diffraction analysis. The derived
      electronic properties are consistent with a zwitterionic molecule, as indicated
      by a charge transfer of 0.82(16) e from the push to the pull moieties and a
      charge polarization of 0.29(7) e on the olefinic bond. A dipole moment of 12(3) D
      has been determined, which compares well with ab initio theoretical results in
      terms of both modulus and orientation. The second moments, which have also been
      obtained with good precision, characterize PPE as a highly quadrupolar molecule.
      The special electronic features of the molecule confer particular topological
      properties to the electron density distribution, as evidenced by comparison with
      "standard" organic molecules. The crystallographic asymmetric unit of the present
      system includes one water molecule, which is hydrogen bonded to PPE. Its
      topological properties have also been investigated, together with an analysis of
      the hydrogen bonds involved.

PMID- 14639637
TI  - Mechanochemical preparation of hydrogen-bonded adducts between the diamine 1,4
      diazabicyclo[2.2.2]octane and dicarboxylic acids of variable chain length: an X
      ray diffraction and solid-state NMR study.
AB  - Mechanical mixing of solid dicarboxylic acids of variable chain length
      HOOC(CH(2))(n)COOH (n = 1-7) with solid 1,4-diazabicyclo[2.2.2]octane generates
      the corresponding salts or co-crystals of the formula [N(CH(2)CH(2))(3)N]-H
      [OOC(CH(2))(n)COOH] (n=1-7). Preparation of the same systems from solution has
      been instrumental for a full characterization of the mechanochemical products by
      means of single-crystal and powder-diffraction X-ray analyses, as well as by
      solid-state NMR. The acid-base adducts, whether involving proton transfer from
      the COOH group to the N-acceptor, that is having ((-))O...H-N((+)) interactions,
      or the formation of neutral O-H...N hydrogen bonds, show a melting point
      alternation phenomenon analogous to that shown by the neutral carboxylic acids.
      The carbon chemical shift tensors of the COOH group obtained from the sideband
      intensity of low speed spinning NMR spectra provide a reliable criterion for
      assigning the protonation state of the adducts.

PMID- 14639638
TI  - Expanded radialenes with bicyclo[4.3.1]decatriene units: new precursors to
      cyclo[n]carbons.
AB  - A new method for the formation of conjugated polyynes has been developed based on
      both the rearrangement of vinylidenes to alkynes and the [2+1] cheletropic
      fragmentation of dialkynylmethylenebicyclo[4.3.1]deca-1,3,5-triene derivatives. A
      model study of the photolysis of simple dialkynylmethylenebicyclo[4.3.1]deca
      1,3,5-trienes resulted in cheletropic fragmentation followed by 1,2-migration to
      give the corresponding linear polyynes, although undesired isomerization to
      methylenebicyclo[5.3.0]triene derivatives took place concurrently. Expanded [3]-,
      [4]-, [5]-, and [6]radialene derivatives with exocyclic bicyclo[4.3.1]decatriene
      units were prepared by oxidative coupling of the monomeric units as precursors to
      the corresponding cyclo[n]carbons, monocyclic forms of carbon clusters. The
      spectroscopic properties of the expanded radialenes were investigated in
      connection with cross conjugation of the core pi system and with its perturbation
      by the extraannular bicyclic pi system. In negative-mode laser-desorption time-of
      flight (LD-TOF) mass spectra, the expanded radialenes exhibited peaks due to the
      corresponding cyclo[n]carbon anions (n = 18, 24, 30, and 36) formed by the
      stepwise loss of the aromatic indane fragments.

PMID- 14639639
TI  - Supramolecular control of the template-induced selective photodimerization of 4
      methyl-7-O-hexylcoumarin.
AB  - A symmetric ditopic molecular receptor (3), containing two identical hydrogen
      bonding recognition subunits, was designed and synthesized. These subunits are
      capable of binding substrates with complementary donor and acceptor sites to form
      a supramolecular complex through hydrogen bonding. Receptor 3 was designed to
      accept two guest molecules, which are held in close proximity within the
      supramolecular species. The substrate molecule, 4-methyl-7-O-hexylcoumarin (1 c),
      forms a 2:1 complex with a binding constant of 150 m(-1) for the second
      substrate, passing first through a 1:1 complex with an affinity constant of 510
      m(-1). The orientation of two molecules of 1 c when bound to the template leads
      to the selective formation of the trans-syn [2+2] photoproduct 2 cB upon
      irradiation. Other photoproducts typically produced in the absence of the
      template are suppressed.

PMID- 14639640
TI  - Chiral bis(amino alcohol)oxalamide gelators-gelation properties and
      supramolecular organization: racemate versus pure enantiomer gelation.
AB  - Four new chiral bis(amino alcohol)oxalamides (1-4: amino alcohol=leucinol,
      valinol, phenylglycinol, and phenylalaninol, respectively) have been prepared as
      low-molecular-weight organic gelators. Their gelation properties towards various
      organic solvents and mixtures were determined and these were then compared to
      related bis(amino acid) oxalamide gelators. Spectroscopic (FTIR, (1)H NMR) and X
      ray diffraction studies revealed that the primary organization motif of (S,S)-1
      and racemate 1 (rac-1) in lipophilic solvents involved the formation of inverse
      bilayers. The X-ray crystal structure of (S,S)-1 also shows this type of bilayer
      organization. The crystal structure of rac-2 reveals meso bilayers of hydrogen
      bonded aggregates. Within the bilayers formed, the gelator molecules are
      connected by cooperative hydrogen bonding between oxalamide units and OH groups,
      while the interbilayer interactions are realized through lipophilic interactions
      between the iBu groups of leucinol. Oxalamide meso-1 lacks any gelation ability
      and crystallizes in monolayers. In dichloromethane rac-1 forms an unstable gel;
      this is prone to crystallization as a result of the formation of symmetrical meso
      bilayers. In contrast, in aromatic solvents rac-1 forms stable gels; this
      indicates that enantiomeric bilayers are formed. Oxalamide rac-1 is capable of
      gelling a volume of toluene three times larger than (S,S)-1. A tranmission
      electron microscopy investigation of rac-1 and (S,S)-1 toluene gels reveals the
      presence of thinner fibers in the former gel, and, hence, a more compact network
      that is capable of immobilizing a larger volume of the solvent. The self-assembly
      of these types of gelator molecules into bilayers and subsequent formation of
      fibrous aggregates can be explained by considering the strength and direction of
      aggregate forces (supramolecular vectors) in three-dimensional space.

PMID- 14639641
TI  - Diamination of olefins: synthesis, structures and reactivity of
      osmaimidazolidines.
AB  - The diamination of certain olefins bearing electron-withdrawing substituents
      proceeds with well-defined bisimido and trisimido complexes of osmium. The
      products are obtained as osmaimidazolidines which are of unprecedented stability
      with regards to olefin functionalisation. Osmium complexes from related
      dihydroxylation or aminohydroxylation are significantly less stable and thereby
      promote catalytic reactions. This difference in reaction profile has been
      investigated and chiral osmium heterocycles obtained from olefin
      difunctionalisation were characterised by X-ray analysis for the first time.
      Kinetic studies on the reaction profile have also been carried out. An asymmetric
      version of this reaction is based on chiral non-racemic auxiliaries and leads to
      diastereomerically enriched osmaimidazolidines with up to 90 % de. This sequence
      represents the first asymmetric diamination of olefins. Attempts on the use of
      chiral ligands for direct asymmetric diamination as well as the consequences of
      osmaimidazolidine properties for a catalytic reaction are discussed.

PMID- 14639642
TI  - Symmetrical electron-deficient materials incorporating azaheterocycles.
AB  - To investigate the potential of di- and tri-azaheterocycles as building blocks
      for pi-conjugated materials with high electron affinity, linear oligomers
      incorporating pyrazine and a C(3)-symmetric discotic molecule based on triazine
      were synthesized. The tridodecyloxyphenyl end-capped ethynylene pyrazinylene
      oligomers showed remarkable solvatochroism in absorption and emission in
      solution. The oligomers containing one and two pyrazine rings displayed liquid
      crystallinity in the solid state. The largest ethynylene pyrazinylene oligomer
      containing three pyrazine rings had the lowest first reduction potential at -1.08
      V. The triazine-derived discotic molecule exhibited UV/Vis and fluorescence
      behavior comparable to that of the linear oligomers and featured a first
      reduction potential at -1.49 V, somewhat lower than expected.

PMID- 14639643
TI  - Photoswitching of the magnetic interaction between a copper(II) ion and a
      nitroxide radical by using a photochromic spin coupler.
AB  - Photoswitching of an intramolecular spin exchange interaction between a
      copper(II) ion and a nitroxyl radical by using a metal complex of diarylethene
      has been studied by means of ESR spectroscopy. As a coordination ligand, a
      diarylethene with a 1,10-phenanthroline ring and nitronyl nitroxide radical was
      synthesized. Mixing the diarylethene ligand with [Cu(hfac)(2)]
      (hfac=hexafluoroacetylacetone) in toluene led to a hypsochromic shift of the
      absorption maxima of the closed-ring isomer due to complexation. ESR measurement
      in toluene at room temperature of the open-ring isomer of the Cu(II) complex gave
      a spectrum that is a superposition of the spectra from the nitroxide radical and
      Cu(II). When the sample was irradiated with 366 nm light, a new peak due to large
      exchange interaction appeared between those of the nitroxyl radical and Cu(II).
      This ESR measurement revealed that the magnitude of the spin exchange interaction
      was changed by more than 160-fold by photoirradiation. This is the largest
      magnetic photoswitching phenomenon recorded in diarylethene systems.

PMID- 14639644
TI  - Electrochemistry of metallofullerene films: the major isomer of Dy@C82.
AB  - Solution-cast films of the major isomer of Dy@C(82) (Dy@C(82)(I)) have been
      studied by cyclic voltammetry (CV) in acetonitrile. The films are found to
      display pronounced and stable redox responses in solution. The
      reduction/reoxidation processes exhibit large splittings between the first two
      reduction and reoxidation waves. However, a pair of reversible oxidation and
      rereduction waves is observed after the reoxidation of a reduced film. The
      characteristics and the inter-relationship of these waves are uncovered by the CV
      technique, scanning electron microscopy (SEM), and UV/Vis-NIR spectra. A possible
      mechanism is proposed for the film electrode processes, which emphasizes the
      redox-induced structural reorganization of the metallofullerene film by the
      incorporation and expulsion of electrolyte ions into and out of the film. The
      influence of the counter ion diffusivity and the ion-pair stability on the
      electrochemical activity of the metallofullerene film has also been indicated.

PMID- 14639646
TI  - Rare-Earth-compound nanowires, nanotubes, and fullerene-like nanoparticles:
      synthesis, characterization, and properties.
AB  - Various low-dimensional nanostructures, such as nanowires, nanotubes, nanosheets,
      and fullerene-like nanoparticles have been selectively synthesized from rare
      earth compounds (hydroxides, fluorides) based on a facile hydrothermal method.
      The subsequent dehydration, sulfidation, and fluoridation processes lead to the
      formation of rare-earth oxide, oxysulfide, and oxyhalide nanostructures, which
      can be functionalized further by doping with other rare-earth ions or by coating
      with metal nanoparticles. Owing to the interesting combination of novel
      nanostructures and functional compounds, these nanostructures can be expected to
      bring new opportunities in the vast research areas of and application in biology,
      catalysts, and optoelectronic devices.

PMID- 14639645
TI  - The convergent synthesis of poly(glycerol-succinic acid) dendritic
      macromolecules.
AB  - The high-yield convergent synthesis of dendrons, dendrimers, and dendritic-linear
      hybrid macromolecules composed of succinic acid, glycerol, and poly(ethylene
      glycol) (PEG) is described. This convergent synthesis relies on two orthogonal
      protecting groups; namely, the benzylidene acetal (bzld) for the protection of
      the 1,3-hydroxyls of glycerol and the tert-butyldiphenylsilyl (TBDPS) ester for
      protection of the carboxylic acid of succinic acid. These novel polyester
      dendritic macromolecules are composed entirely of building blocks known to be
      biocompatible or degradable in vivo to give natural metabolites. Derivatization
      of the dendritic periphery with a methacrylate affords a polymer that can be
      subsequently photo-cross-linked. The three-dimensional cross-linked gels formed
      by ultraviolet irradiation are optically transparent, with mechanical properties
      dependent on the initial cross-linkable dendritic macromolecule.

PMID- 14639647
TI  - Spiroconjugation in spirodicorrolato-dinickel(II).
AB  - In the present work the effect of spiroconjugation on the electronic spectrum of
      the recently synthesized metal complex hexadecaethylspirodicorrolato-dinickel(II)
      (5) (the corrole units in 5 are isoforms) is investigated. To have a suitable
      reference compound at our disposal, tetraethylhexamethylisocorrolato nickel(II)
      (7) has been prepared. On comparing the electronic spectra of this reference
      compound and the spiro-complex, bathochromic shifts of all absorption bands in
      the NIR/Vis-region are observed for the latter as well as marked changes in the
      spectral intensities. A detailed analysis of the spectra supported by
      semiempirical calculations reveals that at least part of the observed changes can
      be unambiguously attributed to the spiro effect. This effect is further affirmed
      by electrochemically measured redox potentials.

PMID- 14639648
TI  - Design of a new mimochrome with unique topology.
AB  - Peptide-based metalloprotein models represent useful systems to help understand
      how metalloproteins can support different functions, by the use of similar metal
      ion cofactors. In order to shed light on the role of the protein matrix in
      modulating the heme properties, we developed new models: mimochromes. They are
      pseudo-C(2) symmetric systems, composed of two helical peptides covalently linked
      to the deuteroporphyrin. The use of C(2) symmetry is particularly advantageous,
      because it simplifies the design, synthesis and characterization. However, it
      leaves the problem of possible diastereomeric forms. In the cobalt complex of the
      first derivative, mimochrome I, Lambda and Delta isomers were indeed
      experimentally observed. All the insights derived from the Co(III)-mimochrome I
      structure were used to obtain a re-designed molecule, mimochrome IV. The
      spectroscopic characterization of the iron and cobalt derivatives suggested the
      presence of the Lambda isomer as unique species. The NMR solution structure of
      the diamagnetic Co(III)-mimochrome IV confirmed the ability of the molecule to
      adopt a unique topology, and revealed the peptide chains to be in helical
      conformation, as designed. The insertion of intramolecular, inter-chain
      interactions was successful in favoring the formation of one of the two possible
      diastereomers. The stereochemically stable structure of mimochrome IV provides an
      attractive model for modulating the redox potential of the heme, by simple
      changing the peptide chain composition around the heme.

PMID- 14639649
TI  - Relative energies of dioxo mu-oxo molybdenum complexes from various fragmentation
      strategies.
AB  - A thiocyanatomolybdenum(VI) dioxo micro-oxo complex dimer bearing 4,4'-di-tBu
      2,2'-bipyridine ligands has shown exceptional oxidizing ability. It exists as a
      meso form (symmetrical) and a d,l pair (unsymmetrical) in the crystal unit cell
      and also in equilibrium in solution. Which oxygen atom and which configuration
      are predominantly involved in the process of oxygen atom transfer is a question
      whose answer would certainly help experimentalists. From ab initio theoretical
      calculations we analyzed the electronic differences between the two
      configurations. The large number of atoms (101) restricts the choice of
      theoretical methods. We give results for second-order Moller-Plesset (MP2) and
      DFT with the hybrid functional B3LYP, with and without pseudopotentials, with
      double-zeta basis sets plus polarization functions. Although the structures of
      the two types of configurations are quite different, we show they have
      practically the same energy. Similarly, no significant differences were found for
      electronic atomic populations on oxygen and surrounding atoms. To facilitate
      future studies on the process of oxygen atom transfer, we compare the entire
      molecules to smaller entities obtained by fragmentations or by so-called hybrid
      methods. We show that the tBu groups, and even sometimes the pyridyl rings, play
      only a minor role in determining the electronic structure. Concerning the energy
      difference between the two configurations, the MP2 results appear more consistent
      than the B3LYP results.

PMID- 14639651
TI  - The silica-like extended polymorphism of cobalt(II) imidazolate three-dimensional
      frameworks: X-ray single-crystal structures and magnetic properties.
AB  - Five polymorphous frameworks of cobalt(II) imidazolates (1-5) have been prepared
      by solvatothermal syntheses. Of these, compound 3 has already been synthesized in
      a gas-phase reaction by Seel et al. in 1969 and structurally characterized by
      Sturm et al. in 1975. The new synthetic strategy affords four polymorphous
      frameworks of cobalt(II) imidazolates (1, 2, 4, 5) of crystalline substances, of
      which the compound 4 (a = b = 23.450(3), c = 12.460(3) A, tetragonal, I4(1)cd, Z
      = 16) is an isomorphous compound of [Zn(im)(2)]( infinity ), which was also
      synthesized in a gas-phase reaction in 1980. The frameworks of compounds 1 and 2
      are porous and isostructural; they have the same framework topology that
      represents a novel uninodal (6,4)-net: 1: a = 18.513(4), b = 24.368(5), c =
      9.2940(19) A, orthorhombic, Fdd2, Z = 16; 2: a = 17.635(4), b = 27.706(6), c =
      9.0810(18) A, orthorhombic, Fdd2, Z = 16. The framework of compound 5 exhibits a
      topology of zeolitic structure with the unit-cell parameters: a = 24.3406(8), b =
      9.4526(3), c = 24.8470(8) A, beta = 91.977(1) degrees, monoclinic, P2(1)/n, Z =
      4. All polymorphous frameworks of cobalt(II) imidazolates reflect the structural
      features of silica (SiO(2)) and also exhibit different magnetic behaviors,
      although the imidazolates transmit the antiferromagnetic coupling between the
      cobalt(II) ions in all cases. However, the uncompensated antiferromagnetic
      couplings arise from spin-canting are sensitive to the structures: compound 1 is
      an antiferromagnet with T(N) = 13.11 K; compounds 2-4 are weak ferromagnets
      (canted antiferromagnets): 2 shows a very weak ferromagnetism below 15 K, 3
      exhibits a relatively strong ferromagnetism below 11.5 K and a coercive field
      (H(C)) of 1800 Oe at 1.8 K, and 4 displays the strongest ferromagnetism of the
      three cobalt imidazolates and demonstrates a T(C) of 15.5 K with a coercive
      field, H(C), of 7300 Oe at 1.8 K. However, compound 5 seems to be a hidden canted
      antiferromagnet with a magnetic ordering temperature of 10.6 K.

PMID- 14639650
TI  - Stereoselectivity of nitrile oxide cycloadditions to chiral allylic fluorides:
      experiment and theory.
AB  - The cycloadditions of nitrile oxides with new and previously studied allylic
      fluorides were examined. The 1,3-dipolar cycloaddition reactions were also
      investigated theoretically with density functional theory (B3LYP) based
      transition-state modelling. The predictions provided reasonable agreement with
      experiment, indicating that both steric and electronic effects have important
      influences on the stereoselectivities of these reactions.

PMID- 14639652
TI  - Monitoring molecular beacon DNA probe hybridization at the single-molecule level.
AB  - We have monitored the reaction dynamics of the DNA hybridization process on a
      liquid/solid interface at the single-molecule level by using a hairpin-type
      molecular beacon DNA probe. Fluorescence images of single DNA probes were
      recorded by using total internal reflection fluorescence microscopy. The
      fluorescence signal of single DNA probes during the hybridization to individual
      complementary DNA probes was monitored over time. Among 400 molecular beacon DNA
      probes that we tracked, 349 molecular beacons (87.5 %) were hybridized quickly
      and showed an abrupt fluorescence increase, while 51 probes (12.5 %) reacted
      slowly, resulting in a gradual fluorescence increase. This ratio stayed about the
      same when varying the concentrations of cDNA in MB hybridization on the
      liquid/surface interface. Statistical data of the 51 single-molecule
      hybridization images showed that there was a multistep hybridization process. Our
      results also showed that photostability for the dye molecules associated with the
      double-stranded hybrids was better than that for those with the single-stranded
      molecular beacon DNA probes. Our results demonstrate the ability to obtain a
      better understanding of DNA hybridization processes using single-molecule
      techniques, which will improve biosensor and biochip development where surface
      immobilized molecular beacon DNA probes provide unique advantages in signal
      transduction.

PMID- 14639654
TI  - A panel of repeat markers for detection of microsatellite instability in murine
      tumors.
AB  - A substantial fraction of human malignancies lack functional DNA mismatch repair
      (MMR), accumulate mutations at high frequency, and exhibit microsatellite
      instability (MSI). In order to distinguish between MMR-competent and MMR
      deficient malignancies, a consensus panel of microsatellite repeats has been
      adopted for MSI analysis of human tumors. There is no reference panel of repeats
      for MSI typing of murine malignancies. In this study, we present six new
      microsatellite repeat markers for MSI typing of mouse tumors. Analysis of
      polymerase chain reaction (PCR)-amplified tumor DNA from MMR-deficient and 
      proficient mice on denaturing polyacrylamide gels revealed that the new panel of
      microsatellites was more sensitive in detecting MSI than six commonly used CA(n)
      repeats. Using the new set of microsatellite markers, we demonstrated the
      presence of MSI in endometrial carcinoma and cancer precursors from
      diethylstilbestrol (DES)-treated mice, pointing to a possible role for loss of
      MMR in hormonally promoted endometrial tumorigenesis.

PMID- 14639655
TI  - Suppression of the transformed phenotype and induction of differentiation-like
      characteristics in cultured ovarian tumor cells by chronic treatment with
      progesterone.
AB  - Epidemiological evidence suggests that elevated levels of the pregnancy hormone
      progesterone might play a role in the reduced risk of women to develop ovarian
      cancer. In vitro studies have supported this hypothesis by demonstrating negative
      effects of this hormone on the growth and proliferation of cultured ovarian
      carcinoma cells. However, little is known about the underlying molecular
      processes and how progesterone might decrease the risk for ovarian tumors.
      Therefore, we investigated the effects of chronic hormone treatment on the cell
      cycle and transformed phenotype of ovarian carcinoma cell lines in vitro. We
      found that long-term treatment of these cells with progesterone caused a
      concomitant reduction of cyclin-dependent kinase (CDK) activity. In parallel,
      these cells lost their transformed phenotype as indicated by the acquisition of
      contact inhibition and the loss of anchorage-independence, as well as the reduced
      expression of tumor markers such as heat shock protein (HSP) 72 and carcinoma
      antigen (CA) 125. In addition, progesterone-treated cells exhibited
      characteristics that resembled a more differentiated phenotype. Taken together,
      our data indicated that progesterone was able to suppress the transformed
      phenotype of ovarian tumor cells. This observation could serve to explain
      progesterone's alleged protective effect in ovarian carcinogenesis.

PMID- 14639656
TI  - Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma.
AB  - Deletion of 11q23 is a common genetic aberration in nasopharyngeal carcinoma
      (NPC). Multiple candidate tumor suppressor genes (TSG) were mapped to this region
      but few of them were investigated in NPC. TSLC1 (tumor suppressor in lung cancer)
      is recently reported to be a putative TSG on 11q23. This gene was found to be
      inactivated by promoter hypermethylation in non-small cell lung carcinoma
      (NSCLC), liver cancer, and breast cancer. To study the role of TSLC1 gene in NPC
      tumorigenesis, we screened for mutations and aberrant methylation of TSLC1 gene
      in 5 NPC cell lines, 3 NPC xenografts, and 38 primary NPC cases. No somatic
      mutations of TSLC1 were detected in the NPC samples, but a 9-bp (CCACCACCA)
      deletion in exon 8 was found in a primary NPC and its corresponding blood sample.
      Bisulfite sequencing revealed aberrant methylation of TSLC1 promoter in four NPC
      cell lines. Loss of TSLC1 gene expression was found in two cell lines (HK-1 and
      CNE-2) with dense methylation. Expression of this gene was restored in these cell
      lines after treatment with demethylating agent 5-aza-2'-deoxycytidine. Our
      results showed that silencing of TSLC1 gene expression in NPC was associated with
      promoter hypermethylation. Promoter hypermethylation of TSLC1 gene was further
      illustrated in 34.2% (13/38) of primary NPCs. No aberrant promoter methylation
      was found in any of the four investigated normal nasopharyngeal epithelia.
      Frequent epigenetic inactivation of TSLC1 gene in NPC suggested that this gene is
      one of the target tumor suppressor genes of this endemic cancer.

PMID- 14639657
TI  - Sequestration of connexin43 in the early endosomes: an early event of Leydig cell
      tumor progression.
AB  - Connexins form gap junction channels that allow intercellular communication
      between neighboring cells. Compelling evidence has revealed that Cx are tumor
      suppressor genes and reduced Cx expression has been related with uncontrolled
      cell growth in tumors and transformed cells. In the present study, we addressed
      Cx transcriptional and posttranscriptional regulations during the earlier stage
      of testicular tumors confined to Leydig cells in a transgenic mice model. In situ
      hybridization indicated that connexin43 (Cx43) mRNA was highly expressed either
      at early tumorogenesis (3 m) characterized by intense proliferation of Leydig
      cells, or at advanced tumorogenesis (6-7 m) when tumor cells completely invaded
      the testis. In contrast, Cx43 protein analyzed by Western blotting or classic
      immunohistochemical analyses was present at the beginning of tumor progression,
      but was dramatically reduced as tumor advanced. Application of high-resolution
      deconvolution microscopy to testis sections demonstrates that cells that
      proliferate exhibited an aberrant cytoplasmic Cx43 localization, in contrast to
      the expected plasma membrane Cx43 localization in normal Leydig cells. Dual
      immunofluorescence labeling with specific markers of cellular compartments shows
      that cytoplasmic Cx43 signal was mainly sequestered within early endosomes.
      Altogether, this study provides the first evidence that impaired Cx43 trafficking
      in endosomes is an early event associated with uncontrolled cell proliferation
      that could serve as a neoplastic marker.

PMID- 14639658
TI  - EGF- and cell-cycle-regulated STAG1/PMEPA1/ERG1.2 belongs to a conserved gene
      family and is overexpressed and amplified in breast and ovarian cancer.
AB  - The abnormal activation of the epidermal growth factor (EGF) pathway is one of
      the most common findings in human cancer, and a number of molecular devices of
      laboratory and clinical relevance have been designed to block this transduction
      pathway. Because of the large number of cellular events that might be regulated
      through the activation of the four EGF receptor family members, it is possible
      that screening methodologies for the identification of new molecular targets
      working downstream of these pathways may provide new tools for cancer diagnosis
      and potentially prevention and therapy. In searching for EGF target genes, we
      have identified ERG1.2, the mouse homolog of the solid tumor-associated gene
      STAG1. Both in humans and in mice, it belongs to a new gene family that can give
      origin to several protein isoforms through alternative splicing and/or multiple
      translation starts. Sequence analysis and experimental data suggest that ERG1.2
      is likely to function as a membrane-bound protein interacting with downstream
      signaling molecules through WW- and SH3-binding domains. ERG1.2 is a cell-cycle
      regulated gene, and both ERG1.2 and STAG1 are induced by EGF and other growth
      factors at the transcript and protein levels. Finally, we have demonstrated that,
      besides prostate cancer and renal cell carcinoma, STAG1 was also overexpressed in
      breast and ovarian cancer cell lines and in breast primary tumors. Although in
      most cases STAG1 overexpression is probably due to the abnormal activation of the
      EGF pathway, we have also demonstrated genetic amplification and rearrangement of
      its locus in one breast cancer cell line and one primary ovarian cancer,
      suggesting that STAG1 might be a direct molecular target in the carcinogenetic
      process. Thus its overexpression might be regarded not only as a tumor marker but
      also as a potentially pathogenetic event.

PMID- 14639659
TI  - TP53 is frequently altered by methylation, mutation, and/or deletion in acute
      lymphoblastic leukaemia.
AB  - Different mechanisms, such as chromosomal rearrangements, deletions, mutations,
      and methylation/demethylation of the promoter regions of genes, have been shown
      to be involved in acute lymphoblastic leukaemia (ALL). These genetic and
      epigenetic alterations lead to the activation of protooncogenes or to
      inactivation of tumour suppressor genes promoting cell proliferation. One of the
      most frequently inactivated tumour suppressor genes is TP53, which is altered in
      50% of human tumours. In this study, we have analysed: (1) the complete coding
      region, all intron-exon junctions and noncoding regions of exons 1-11 of TP53 by
      lexon-DGGE; (2) the methylation status of the 5' region of TP53 and (3) the
      deletion of one or both alleles of the gene by fluorescence in situ hybridisation
      (FISH) in 57 ALL patients. Using these techniques, we have found promoter
      methylation in 32% of the cases, missense mutations in 8.8%, and deletion of one
      allele in 7.5% of the samples, with TP53 being altered in 40% of the ALL samples
      studied in this series.

PMID- 14639660
TI  - What is the evidence that Ecstasy (MDMA) can cause Parkinson's disease?

PMID- 14639661
TI  - Corticobasal degeneration as a cognitive disorder.
AB  - The presence of cognitive impairment in corticobasal degeneration (CBD) is now
      widely recognised. Our review of the literature reveals that, although the
      pattern and severity of neuropsychological impairments can be highly variable
      across patients, several general trends can be identified. The most
      characteristic impairments are limb apraxia (usually ideomotor), constructional
      and visuospatial difficulties, acalculia, frontal dysfunction, and nonfluent
      aphasia. The limb apraxia is associated with deficits in drawing, copying, and
      handwriting, but there is emerging evidence that the problems with handwriting
      are not due exclusively to the apraxia. The findings with respect to episodic
      memory are more variable, but when there is impairment in this area, it tends to
      be milder than that seen in Alzheimer's disease. Semantic memory functioning
      appears relatively preserved but has been poorly studied. Problems with speech
      are common, and may be due to dysarthria or buccofacial apraxia. Aphasia,
      although initially considered rare, is in fact a common accompaniment of CBD, may
      be the presenting feature, and is typically nonfluent in type. More systematic
      investigation of the clinical and neuropathological overlap between progressive
      nonfluent aphasia (generally considered to be a form of frontotemporal dementia)
      and CBD is needed.

PMID- 14639662
TI  - Case-control study of the alpha-synuclein interacting protein gene and
      Parkinson's disease.
AB  - We conducted a case-control study of the alpha-synuclein-interacting protein gene
      (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319
      PD cases and 195 controls were genotyped for four SNCAIP variants, including a
      microsatellite repeat in intron 4 and three restriction fragment length
      polymorphisms (RFLP) proximal to the 5' terminal of exons 1, 4, and 6. None of
      the variants were found associated with PD overall. Global score statistics were
      not significant for four, three, and two loci haplotypes. All four loci were in
      linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001).
      Recursive partitioning showed no interactions between variants of the SNCAIP gene
      and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene.

PMID- 14639663
TI  - Suggestive linkage to chromosome 19 in a large Cuban family with late-onset
      Parkinson's disease.
AB  - The identification of disease genes using family-based approaches has provided
      important insights into the pathogenesis of Parkinson's disease (PD)
      demonstrating the importance of genetic studies on monogenic forms of the
      disease. We studied a large Cuban family with typical, late-onset PD and probable
      autosomal dominant inheritance. Mean age at onset was 61.2 years (+/- 12.53, 45
      76). Other phenotypes such as essential tremor and atypical parkinsonism were
      observed in this family. We carried out a genome-wide scan and linkage analyses.
      The genetic data were analyzed using a conservative model in which only patients
      with clinically definite or likely PD were considered affected, other phenotypes
      were regarded as "unknown." Multipoint analyses yielded a maximum LOD of 2.26
      between markers D19S221 and D19S840. Haplotype analysis showed a region on
      chromosome 19 shared by six of seven PD patients. The essential tremor phenotype
      and the atypical parkinsonism do not segregate with this haplotype, suggesting a
      different etiology. Our findings suggest the presence of a novel locus for PD on
      chromosome 19p13.3-q12. We propose that an oligogenic model with moderate
      contribution of two or three genes rather than a "pure" monogenic model might
      explain better the wide range in age at onset, the reduced penetrance and the
      phenotypical variability observed in PD families.

PMID- 14639664
TI  - Young- versus older-onset Parkinson's disease: impact of disease and psychosocial
      consequences.
AB  - The effect of Parkinson's disease (PD) on young patients' lives is likely to
      differ from that in older patients. For this study, 75 patients with onset of PD
      before the age of 50 and 66 patients with later onset completed a booklet of
      questionnaires on demographic and clinical variables, quality of life, and
      psychosocial factors. Apart from a higher rate of treatment-related dyskinesias
      in the younger onset group, the two groups did not differ in self-reported
      disease severity or disability. A higher percentage of young-onset patients was
      unemployed due to disability or had retired early. Quality of life as measured on
      the PDQ-39 was significantly worse in young-onset patients than in older-onset
      patients. Young-onset patients also had worse scores on the stigma and marital
      satisfaction scales, and were depressed more frequently. Differences between the
      two groups in their most commonly employed coping strategies and in terms of
      their satisfaction with emotional support did not reach significance. We conclude
      that young-onset patients more frequently experience loss of employment,
      disruption of family life, greater perceived stigmatization, and depression than
      do older-onset patients with PD. In addition to more severe treatment-related
      motor complications, social and psychosocial factors may contribute to greater
      impairment of quality of life in young patients with PD.

PMID- 14639665
TI  - A computer model of rigidity and related motor dysfunction in Parkinson's
      disease.
AB  - This work explores the involvement of spinal circuits in the generation of
      parkinsonian rigidity and related motor dysfunction. A computer model of spinal
      proprioceptive input processing, derived from previous work on spasticity
      modeling, was adapted to the simulation of parkinsonian rigidity. Model
      parameters were varied to generate simulations reproducing experimental data
      obtained using the pendulum test of the leg in 10 parkinsonian patients and 3
      healthy subjects. Convenient reproductions of experimental traces in rigidity
      were obtained by the combination of a low reflex gain and a decrease in reflex
      threshold. These findings are consistent with studies reporting an increase of
      spinal interneuron excitability and proprioception deficits in Parkinson's
      disease (PD). Moreover, as the threshold parameter was much lowered, our model
      generated typical features of parkinsonian resting tremor, endorsing the
      hypothesis of a participation of a spinal oscillator in this disorder. Finally,
      tuning the reflex gain during simulations of rigidity resulted in the generation
      of active movement, opening some hypotheses on pathophysiology of motor
      dysfunction in PD, and notably, of akinesia. More generally, this work accredits
      the hypothesis of the involvement of an aperiodic, altered supra-spinal motor
      drive in PD, resulting in spinal dysfunction, through specific descending motor
      pathways. This may lead to a search for new (spinal) pharmacological targets in
      PD. It emphasizes further the value of computer modeling in understanding motor
      control in health and disease.

PMID- 14639666
TI  - Measuring the rate of progression of Parkinson's disease over a 5-year period
      with beta-CIT SPECT.
AB  - Recent imaging studies suggest a rapid degeneration of the dopaminergic system in
      early Parkinson's disease (PD), followed by a slowing of the degenerative process
      in advanced disease. In the present study, a group of early-stage PD patients
      underwent three sequential [123I]beta-CIT SPECT studies to assess the decline of
      striatal dopamine transporter binding over a 5-year period. Twenty-one of a
      cohort of 24 early PD patients who participated in an earlier longitudinal beta
      CIT SPECT imaging study [Mov Disord 2002;17:45-53] were included. Scan intervals
      were 26 +/- 11 months (scan 1-2) and 38 +/- 15 months (scan 2-3), respectively.
      The relative annual rate of decline of striatal beta-CIT binding from age
      expected normal values at the time of Scan 1 was used as primary outcome
      variable. The relative annual decline of striatal binding from Scan 1 to Scan 2
      (4.5 +/- 4.6%) and from Scan 2 to Scan 3 (3.0 +/- 3.0%) was not significantly
      different. The non-significant difference in progression rate was due mainly to
      the rapid early decline of striatal binding in 1 patient who subsequently
      developed a severe dysexecutive dementia syndrome. These data are not suggestive
      of substantial change in the course of dopaminergic degeneration in PD within the
      first 5 to 7 years after symptom onset.

PMID- 14639667
TI  - Diagnostic potential of acoustic startle reflex, acoustic blink reflex, and
      electro-oculography in progressive supranuclear palsy: a prospective study.
AB  - We carried out a prospective study to analyze the diagnostic potential of
      acoustic startle reflex (ASR), acoustic blink reflex (ABR) and electro
      oculography (EOG) in early stages of atypical parkinsonian syndrome. The study
      was carried out in a consecutive series of 41 patients clinically diagnosed as
      atypical parkinsonism (mean time from first symptoms of 38 months and follow-up
      of 26 months). The three procedures were carried out immediately after the first
      clinical evaluation. ASR and ABR were elicited by auditory stimuli while the
      patient was attending to a simple reaction time task. Outcome measures were: ASR
      (absence/presence, latency), ABR (absence/presence, latency) and EOG
      (suggestive/not suggestive of progressive supranuclear palsy [PSP]). Final
      clinical diagnosis was carried out by two neurologists blind to the
      neurophysiological results. A study of diagnostic sensitivity and odds ratio (OR)
      calculation for the PSP diagnosis was carried out. Neurophysiological examination
      showed the following sensitivity/specificity (%) for the diagnosis of PSP: ASR:
      100/89; ABR 85/89; EOG 100/72. OR values were: ASR: 0.011; ABR: 0.037; EOG:
      0.038. The three tests taken simultaneously showed a sensitivity of 100% and a
      specificity of 95%. The three neurophysiological tests investigated provided
      sensitive and specific measures with predictor value in early stages of atypical
      parkinsonian syndrome.

PMID- 14639668
TI  - Effect of ethanol on the central oscillator in essential tremor.
AB  - We investigated the effects of ethanol and diazepam on the central, mechanical,
      and mechanical reflex components of tremor in patients with essential tremor
      (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2
      separate days. Dose of ethanol or diazepam was calculated in each individual
      according to height, weight, and age in 10 patients with ET. The postural tremor
      amplitude at the wrist was recorded using a three-dimensional accelerometer
      placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface
      electrodes placed on the forearm extensors and flexors. To separate central and
      mechanical (reflex) components, a 500-g weight was placed on the dorsum of the
      hand during a second tremor measurement. Tremor recordings were done at baseline
      and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood
      levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood
      ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude
      of the central component 60 minutes after ingestion of ethanol was decreased
      significantly (P = 0.029) compared with diazepam. Our findings suggest that the
      improvement in tremor after ethanol ingestion was due, at least in part, to an
      effect on a central oscillator.

PMID- 14639669
TI  - Perceptual differences in sequential stimuli across patients with musician's and
      writer's cramp.
AB  - Previous research has demonstrated a relationship between the regularity of motor
      production and the ability to make accurate perceptual judgments. The current
      study investigated the temporal abilities of two groups of patients with known
      movement problems (musicians' and writers' cramp), some of whom have had many
      years of training in temporal discrimination. Patients and controls (musician and
      nonmusician, respectively) judged whether the last of six sequential auditory or
      tactile stimuli occurred earlier or later in comparison to five previously and
      regularly presented stimuli. In both sensory domains, patients with musicians'
      cramp detected the early stimulus better than controls. When detecting the onset
      of late stimuli, only in the auditory domain were patients worse than controls.
      Patients with writers' cramp, however, did not show any significant group
      differences in either auditory or tactile domains, suggesting that such patients
      are not deficient in processing sequential stimuli. In conclusion, compared to
      controls, patients with musician's cramp demonstrated generalized timing
      anomalies, occurring in the symptomatic (tactile) and the asymptomatic (auditory)
      sensory domains. This timing problem is likely to be a consequence of the
      dystonic symptoms rather than the cause.

PMID- 14639670
TI  - Separate ipsilateral and contralateral corticospinal projections in congenital
      mirror movements: Neurophysiological evidence and significance for motor
      rehabilitation.
AB  - The neurophysiological hallmark of congenital mirror movements (MM) are fast
      conducting corticospinal projections from the hand area of one primary motor
      cortex to both sides of the spinal cord. It is still unclear whether the abnormal
      ipsilateral projection originates through branching fibres from the normal
      contralateral projection or constitutes a separate ipsilateral projection. To
      clarify this question, we used focal paired-pulse transcranial magnetic
      stimulation to test task-related modulation of short-interval intracortical
      inhibition (SICI) in the abductor pollicis brevis (APB) muscles of a 15-year-old
      girl (Patient 1) and a 40-year-old woman (Patient 2) with congenital MM. In both
      patients, during intended unilateral APB contraction, SICI decreased markedly in
      the "task" APB but remained unchanged in the "mirror" APB when compared to muscle
      rest. In contrast, spinal excitability as tested with H reflexes increased
      similarly in the task and mirror flexor carpi radialis muscles. This dissociation
      of task-related SICI modulation strongly supports the existence of a separate
      ipsilateral fast-conducting corticospinal projection. In Patient 1, we tested the
      functional significance of this separate ipsilateral projection during 7 months
      of motor rehabilitation training, which was designed to facilitate unilateral
      finger movements. A marked reduction of MM was observed after training,
      suggesting that unwanted mirror activity in the ipsilateral pathway can be
      suppressed by learning.

PMID- 14639671
TI  - Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa
      and ropinirole in the MPTP-lesioned marmoset.
AB  - Long-term dopamine replacement therapy of Parkinson's disease leads to the
      occurrence of dyskinesias. Altered firing patterns of neurons of the internal
      globus pallidus, involving a pathological synchronization/desynchronization
      process, may contribute significantly to the genesis of dyskinesia.
      Levetiracetam, an antiepileptic drug that counteracts neuronal
      (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP
      lesioned marmoset model of Parkinson's disease, after coadministration with (1)
      levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of
      levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or
      L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with
      significantly less dyskinesia, in comparison to L-dopa monotherapy during the
      first hour after administration. Thus, new nondopaminergic treatment strategies
      targeting normalization of abnormal firing patterns in basal ganglia structures
      may prove useful as an adjunct to reduce dyskinesia induced by dopamine
      replacement therapy without affecting its antiparkinsonian action.

PMID- 14639672
TI  - Parkin variants in North American Parkinson's disease: cases and controls.
AB  - We report on an evaluation of coding variants within the parkin gene to assess
      their frequency in a North American clinical series of 313 Parkinson's disease
      (PD) cases and 192 unrelated controls. We hypothesized that the carrier frequency
      of parkin coding mutations, exon deletions, or duplications may be greater in PD
      cases. However, point mutations and exonic deletions/duplications, reported
      previously as pathogenic in homozygous or compound heterozygous individuals,
      occurred in both cases and controls with similar frequencies (3.8% in cases, 3.1%
      in controls). Furthermore, only stratified subanalyses detected any genetic
      association between the V380L common coding polymorphism and PD. We discuss the
      implication of parkin mutations for Parkinson's disease from this population
      perspective.

PMID- 14639673
TI  - Survival time, mortality, and cause of death in elderly patients with Parkinson's
      disease: a 9-year follow-up.
AB  - This community-based study of Parkinson's disease (PD) investigated age at death
      and cause of death in a cohort of 170 previously studied patients. The current
      study is a 9-year follow-up, and the results are compared to 510 sex- and age
      matched controls from the same area. A total of 170 patients were diagnosed with
      PD on August 31, 1989, within a defined area of Sweden. A control group of 510
      persons from the same area and with the same age and sex distribution was also
      examined regarding age at death and cause of death. After 9.4 years, 121 cases
      (71.1%) and 229 controls (44.9%) were no longer alive. Thus, the mortality rate
      ratio was 1.6 (95% confidence interval [CI], 1.3-1.8) when comparing PD patients
      with controls. The all-cause hazard ratio for cases compared to controls was 2.4
      (95% CI, 1.9-3.0). The mean age at death for the cases was 81.9 (95% CI, 80.3
      83.0) years and for the controls 82.9 (95% CI, 82.0-83.7) years. Survival
      analysis also showed a shorter survival time (P < 0.001) for PD patients. Only
      53% of the death certificates for the deceased patients recorded PD as an
      underlying or contributory cause of death. Many PD patients reached a high age
      but had a shorter survival than the controls. There was a significant increase in
      deaths from pneumonia.

PMID- 14639674
TI  - Abnormal sensorimotor integration is related to disease severity in Parkinson's
      disease: a TMS study.
AB  - Hyperexcitability of the motor system has been reported in Parkinson's disease
      (PD). We evaluate how cutaneous afferents modulate motor excitability in PD
      patients and whether abnormal modulation is correlated to parkinsonian symptoms.
      Digital stimulation causes abnormal enhancement of motor responses in patients.
      This effect may be one of the features of motor hyperexcitability in PD.
      Cutaneomotor hyperexcitability correlates with clinical scores, suggesting that
      abnormal processing of cutaneous inputs might contribute to the pathogenesis of
      parkinsonian symptoms.

PMID- 14639675
TI  - Randomized, double-blind, 3-month parallel study of the effects of pramipexole,
      pergolide, and placebo on Parkinsonian tremor.
AB  - We compared the antitremor effect of pramipexole, pergolide, or placebo in
      Parkinson's disease (PD). A double-blind, randomly controlled, parallel protocol
      was deployed to examine the effects of placebo, pergolide, and pramipexole [doses
      escalated to 1.5 mg three times daily (t.i.d.) over 3 months] on a compound
      Tremor Index (TI) and Unified Parkinson's Disease Rating Scale (UPDRS) part III.
      Thirty PD patients (19 men, 11 women; mean age 69 years, range 54-80 years; mean
      disease duration 3.9 years, range, 0.5-10 years) participated in the study, with
      10 patients in each arm. Six subjects failed to complete the study (4 on
      pergolide and 2 on placebo). Analysis of covariance demonstrated strong evidence
      for a treatment effect on both TI and UPDRS III. There was no significant
      difference between the active treatments on either TI or UPDRS III. Both
      pergolide and pramipexole were significantly better than placebo. The results
      indicate that pergolide and pramipexole (1.5 mg t.i.d.) have similar anti-PD
      tremor and UPDRS III actions that are significantly superior to placebo. Patients
      on pergolide were more likely to drop out because of adverse events than those on
      pramipexole.

PMID- 14639676
TI  - Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease.
AB  - We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation
      (STN-DBS) who were evaluated 6 months after the surgical procedure using the
      Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test.
      Additional follow-up was available in 32 patients after 12 months and in 20
      patients after 24 months. At 6 months follow-up, STN-DBS reduced the UPDRS motor
      score by 50.9% compared to baseline. This improvement remained constant at 12
      months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN
      DBS included intraoperative subdural hematoma without neurological sequelae (n =
      1), minor intracerebral bleeding with slight transient hemiparesis (n = 1),
      dislocation of impulse generator (n = 2), transient perioperative confusional
      symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic
      behaviour (n = 2), and transient manic psychosis (n = 1). One patient died
      because of heart failure during the first postoperative year. The current series
      demonstrates efficacy and safety of STN-DBS beyond the first year after surgical
      procedure. Complications of STN-DBS comprise a wide range of psychiatric adverse
      events which, however, were temporary.

PMID- 14639677
TI  - Body weight gain rate in patients with Parkinson's disease and deep brain
      stimulation.
AB  - We evaluated body weight changes in patients with Parkinson's disease (PD) after
      electrode implantation for deep brain stimulation (DBS) in the subthalamic
      nucleus (STN) in relation to clinical improvement. Thirty PD patients who
      received STN DBS were included (22 men, 8 women; mean age, 60.0 +/- 7.1 years;
      mean PD duration, 13.5 +/- 3.7 years; mean body mass index [BMI], 21.6 +/- 3.0
      kg/m2). Body weight, physical activity, and Unified Parkinson's Disease Rating
      Scale (UPDRS) scores were noted before and 3 and 12 months after the procedure.
      Significant weight gain occurred in 29 patients; the mean increase was 14.8 +/-
      9.8% of initial body weight in 1 year. Of the patients, 46.5% reported weight
      gain in the first 3 months, 21.4% gradual weight gain in the first 6 months, and
      32.1% a slow increase for 1 year. Mean BMI increased up to 24.7 +/- 3.7 kg/m2.
      After 1 year, mean UPDRS motor score improved significantly in off and in on; and
      therapy complications improved by 91.0 +/- 17.0%. BMI changes at 3 and 12 months
      were significantly correlated to dyskinesia score changes, and levodopa dosage
      was not. In PD, STN DBS produces not only symptom control, but also weight gain.
      DBS candidates should be given nutritional counseling before the intervention to
      prevent rapid and/or excessive weight gain.

PMID- 14639678
TI  - Subthalamic somatosensory evoked potentials in Parkinson's disease.
AB  - Deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective
      treatment for advanced Parkinson's disease. It also provides an opportunity to
      record neural activity from the human basal ganglia. In this study, to
      investigate the involvement of the human STN in sensory functions, we recorded
      somatosensory evoked potentials (SEPs) elicited by contralateral median-nerve
      stimulation, from STN electrodes implanted for DBS in patients with Parkinson's
      disease. We suggest that the STN N18 component of SEPs in Parkinson's disease is
      a mainly local field potential elicited by muscle afferent input to the nucleus.

PMID- 14639679
TI  - Coherence analysis in the myoclonus of corticobasal degeneration.
AB  - We investigated whether myoclonus in corticobasal degeneration (CBD) is cortical
      or subcortical in origin. Many authors have suggested that the myoclonus in CBD
      is a subtype of cortical myoclonus, despite the fact that back-averaging fails to
      detect a cortical correlate to spontaneous or action induced jerks and giant
      sensory evoked potentials are seldom found. Electroencephalographic
      electromyographic (EEG-EMG) and EMG-EMG frequency analysis may be more sensitive
      to cortical drives when EMG bursts occur at a high frequency and at low
      amplitudes as in CBD. We evaluated EEG-EMG and EMG-EMG coherence and phase in 5
      patients with clinically probable CBD and unilateral, action-induced and stimulus
      sensitive myoclonus. We found negligible corticomuscular coherence despite a
      dramatically exaggerated EMG-EMG coherence. We conclude that an inflated EMG-EMG
      coherence is found in some patients with CBD and that this is unlikely to be due
      to an exaggerated cortical drive.

PMID- 14639680
TI  - Pure akinesia: an unusual phenotype of Hallervorden-Spatz syndrome.
AB  - Two siblings were seen in our outpatient movement disorders clinic with an
      indolent clinical picture of a pure akinesia syndrome. Magnetic resonance showed
      the typical "eye of the tiger" sign, and genetic screening disclosed that both
      siblings were compound heterozygotes with two missense mutations in the PANK2
      gene 734A-->G and 1172T-->C. This case report highlights the phenotypic diversity
      of Hallervorden Spatz syndrome and the need for further investigation of adult
      onset pure akinesia syndromes.

PMID- 14639681
TI  - Mesencephalic cryptococcal abscesses presenting with parkinsonism as an initial
      manifestation of AIDS.
AB  - Parkinsonism has been associated with HIV/AIDS and cerebral cryptococcal disease,
      but to date there has been no report of histological cryptococcal lesions in the
      substantia nigra (SN) in a patient with parkinsonism. We report on a case of a 63
      year-old man who presented with tremor, gait disturbance, and mask-like facies,
      and showed cryptococcal meningoencephalitis with cryptococcal abscesses in the SN
      at autopsy, without Lewy bodies or significant degeneration of the SN neurons.
      Parkinsonism also represented the first manifestation of AIDS in this previously
      undiagnosed patient. This case highlights the importance of considering
      infectious etiologies in patients presenting with parkinsonism, and underscores
      the need for autopsy in evaluation of patients with new or unexplained movement
      disorders. Movement disorders in association with AIDS and mesencephalic mass
      lesions are discussed.

PMID- 14639682
TI  - Automated assessment of cervical dystonia.
AB  - We developed an automated and objective method to measure posture and voluntary
      movements in patients with cervical dystonia using Fastrack, an electromagnetic
      system consisting of a stationary transmitter station and four sensors. The
      junction lines between the sensors attached to the head produced geometrical
      figures on which the corresponding aspects of the head were superimposed. The
      head position in the space was reconstructed and observed from axial, sagittal,
      and coronal planes. Four patients with cervical dystonia and 6 healthy subjects
      were studied. Each patient was representative of one of the typical patterns of
      cervical dystonia. The study allowed the authors to collect quantitative data on
      posture and range of motion of the head. This pilot study demonstrates the
      efficacy of the Fastrack system to objectively measure the head position in
      cervical dystonia patients.

PMID- 14639683
TI  - Impaired heteronymous somatosensory motor cortical inhibition in dystonia.
AB  - A typical pathophysiological abnormality in dystonia is cocontraction of
      antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal
      cord. Recent experimental data have shown that inhibitory interactions between
      antagonist muscles have also a parallel control at the level of the sensorimotor
      cortex. The aim of this work was to study heteronymous effects of a median nerve
      stimulus on the corticospinal projections to forearm muscles in dystonia. We used
      the technique of antagonist cortical inhibition, which assesses the conditioning
      effect of median nerve afferent input on motor evoked potentials (MEPs) elicited
      by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor
      muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia
      participated in the study. MEPs and somatosensory evoked potentials were normal
      in patients. In healthy subjects, median nerve stimulation at 15- to 18-msec
      intervals inhibited the test MEPs in forearm extensors. In dystonic patients,
      median nerve stimulation delivered at the same conditioning-test intervals
      elicited significantly less inhibition of the test MEP. On the whole, these data
      suggest an impaired sensory-motor integration in dystonia and, more specifically,
      the decreased antagonistic cortical inhibition could suggest that functional
      interactions between antagonist muscles are primarily impaired at the cortical
      level.

PMID- 14639684
TI  - Treatment of Sydenham chorea with corticosteroids.
AB  - Despite treatment with valproic acid and neuroleptics, a significant proportion
      of patients with Sydenham chorea (SC) remain with chorea. We evaluated the effect
      of intravenous methyl-prednisolone followed by oral prednisone in patients with
      SC refractory to conventional treatment. Patients were enrolled in the study if
      they failed to improve with conventional treatment, despite the development of
      side effects. Chorea was rated on a 0 to 4 score. Five patients, 3 of them women,
      were included in the study. The median pretreatment rating score of the chorea
      was 3 (range, 3-4) and dropped to 1 (range, 0-2) after a median follow-up of 7
      months (range, 3-7 months). Two patients developed Cushing syndrome. Our data
      suggest that intravenous methyl-prednisolone followed by oral prednisone is an
      effective and well-tolerated treatment of refractory SC.

PMID- 14639685
TI  - Rapidly progressive parkinsonism in a self-reported user of ecstasy and other
      drugs.
AB  - A 38-year-old man developed parkinsonism that progressed to Hoehn and Yahr stage
      5 within 4 years of onset. Response to ropinirole deteriorated, levodopa was not
      tolerated, and subthalamic nucleus stimulation has provided only partial relief
      of symptoms. He reported heavy use of Ecstasy through most of his twenties and
      thirties. His neurological problems may be unrelated to his drug use, but it is
      also possible they represent an idiosyncratic reaction.

PMID- 14639686
TI  - Severe cervical dystonia in pathologically proven Parkinson's disease and
      dementia.
AB  - We describe and present a videotape of a patient with parkinsonism and dementia
      who developed severe cervical dystonia, despite treatment with levodopa and
      botulinum toxin. The clinical diagnosis of Parkinson's disease and dementia (PDD)
      was confirmed at autopsy.

PMID- 14639687
TI  - Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation
      in a patient with Parkinson's disease.
AB  - Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established
      therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms
      induced by STN-DBS occurred in a previously psychiatrically healthy patient,
      focusing on the role of STN-DBS in influencing not only motor but also emotional
      behaviour.

PMID- 14639688
TI  - Interleukin-1A (-889) genetic polymorphism increases the risk of multiple system
      atrophy.
AB  - In a case-control study using a clinically well-defined group of 30 multiple
      system atrophy (MSA) patients and 110 control subjects, homozygosity for
      interleukin-1A (IL-1A) allele 2 (high secretor of proinflammatory cytokine) in
      the regulatory region (-889) of the IL-1A gene was associated with a fivefold
      increased risk for MSA.

PMID- 14639689
TI  - Olfaction in essential tremor patients with and without isolated rest tremor.
AB  - An olfactory deficit is present in patients with essential tremor (ET), but it is
      often milder than that in patients with Parkinson's disease (PD). In both, the
      deficit occurs early in the disease. Isolated rest tremor without other signs of
      parkinsonism can occur in patients with ET. If the rest tremor in these patients
      represents a manifestation of ET rather than early PD, we hypothesized that their
      University of Pennsylvania Smell Identification Test (UPSIT) scores would be
      similar to those of ET patients without rest tremor. The mean UPSIT score in 13
      ET patients with isolated rest tremor did not differ from that of 58 ET patients
      without rest tremor (29.3 +/- 4.3 vs. 29.4 +/- 6.4; P = 0.69). Several ET
      patients with rest tremor had UPSIT scores that fell outside of the range that is
      seen in 95% of patients with PD. These data raise the possibility that some ET
      patients with isolated rest tremor may not have early PD and that the
      pathological process that is responsible for their ET is also involving the basal
      ganglia.

PMID- 14639690
TI  - Prevalence of primary late-onset focal dystonia in the Belgrade population.
AB  - The aim of this cross-sectional study was to estimate the prevalence of different
      subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia),
      Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of
      dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000
      population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type
      specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for
      cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9
      per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively.

PMID- 14639691
TI  - Pilot study of effect of emotional stimuli on tic severity in children with
      Tourette's syndrome.
AB  - To assess objectively the effects of emotional stimuli on the severity of tics
      and to determine if such effects were mediated by the autonomic nervous system,
      we carried out videotape ratings of tics and electrophysiological monitoring of
      heart beat and respiration on 4 children with Tourette's syndrome while they were
      watching a movie known to elicit emotional responses relevant to normal childhood
      events. Measured tic severity was highest during periods associated with
      anticipation, resolution of emotional changes, and lower concentration, lowest
      during periods of anger and happiness, and intermediate during periods of sadness
      and fear. Tic severity did not correlate with heart or respiratory rate. Thus,
      tics seem influenced differentially by various emotional states, but this effect
      does not seem to be autonomically mediated.

PMID- 14639692
TI  - Psychogenic movement disorders in two children.
AB  - Two schoolboys with diagnostic criteria for psychogenic movement disorder (PMD)
      are described: one with bizarre tremor of the right hand and a very slow and
      cautious gait, another with exaggerated trunk sway and collapses during standing
      and walking.

PMID- 14639693
TI  - Arm chorea secondary to an unruptured giant aneurysm.
AB  - We describe the case of a 20-year-old male who developed right-arm choreic
      movements secondary to a giant unruptured aneurysm impinging upon the left
      thalamus, putamen, globus pallidus, cerebral peduncle, midbrain, and subthalamic
      nucleus. The aneurysm was treated successfully with coils and a supraclinoid
      balloon. Abnormal movements initially failed to ameliorate, but within a few
      months, it was possible to discontinue symptomatic haloperidol therapy, with only
      mild residual abnormal movements.

PMID- 14639695
TI  - Subthalamic lesion and paroxysmal tonic spasms.
AB  - Paroxysmal dyskinesia due to a subthalamic lesion is a rare finding. We describe
      a patient with paroxysmal tonic spasms due to a well-defined lesion in the
      subthalamic area. In this case, we confirm the nonepileptic nature of the episode
      and collect with detail the clinical features by means of a video
      electroencephalographic recording. We also report an excellent response to
      carbamazepine in subthalamic paroxysmal dyskinesias.

PMID- 14639694
TI  - Transient ischemic attacks presenting as hemiballism.
AB  - Hemiballism is continuous, nonpatterned involuntary movement characterized by
      irregular, coarse, flinging movement involving the limbs on one side. Hemiballism
      is most commonly caused by stroke. However, very rarely a transient ischemic
      attack (TIA) presents as hemiballism. We describe 2 such patients with
      hemiballism presenting as TIA.

PMID- 14639696
TI  - Periodic limb movement during sleep developed after pontine lesion.
AB  - We describe 2 patients who suffered a pontine infarction and subsequently
      developed periodic leg movement (PLM). The temporal relationship between a stroke
      and subsequent PLM, as well as the absence of sleep-related disorders in
      patients' histories, favors the argument of a cause-and-effect relationship, with
      the observed association providing evidence for an anatomic substrate for PLM.

PMID- 14639697
TI  - Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular
      genetic study.
AB  - We report on a patient with adult-onset Niemann-Pick type C (NPC) disease,
      carrying the mutations P1007 and I1061T in the NPC1 gene, presenting with marked
      psychiatric changes followed by dystonia and cognitive impairment. Filipin
      staining, single photon emission computed tomography perfusional, positron
      emission tomography metabolic, conventional magnetic resonance imaging, and
      magnetic resonance spectroscopy findings suggested a pathophysiological
      correlation with phenotype expression. This case expands the clinical and genetic
      spectrum of the rare adult-onset NPC disease phenotype.

PMID- 14639698
TI  - Multipoint linkage disequilibrium mapping for complex diseases.
AB  - Linkage disequilibrium (LD) or association studies using case-parent trios have
      become a common approach to locate unobserved susceptibility genes underlying
      complex diseases. With the availability of ever more dense marker maps, how to
      utilize the information carried by multiple markers simultaneously remains
      challenging. Recently, Liang et al. ([2001a] Am. J. Hum. Genet. 68: 937-950)
      proposed a multipoint LD method to estimate the location of a susceptibility gene
      within a framework map along with its sampling uncertainty. Two important
      features of this method are that 1) it uses all trios whether parents are
      heterozygous for a given marker or not, and 2) it provides a single test
      statistic for the null hypothesis of no linkage or no LD to the region, avoiding
      the multiple testing problem encountered when performing individual transmission
      disequilibrium tests (TDT) for each marker individually. In this paper, we
      discuss how this method can be expanded to address important issues pertaining to
      complex diseases in a unified fashion. These issues include, among others, gene
      gene and gene-environment interactions, genetic heterogeneity, phenotypic
      refinement, and paternal vs. maternal transmission. We applied this method to
      asthmatic case-parent trios from the Collaborative Study on the Genetics of
      Asthma (CSGA), and found that the previous evidence for linkage and LD in a 13.6
      cM region of chromosome 11 can be attributed to maternal transmission, while
      there was no evidence of excess paternal transmission. Furthermore, such
      discrepancy in preferential transmission was most evident among probands with
      early onset age (6 years old or younger).

PMID- 14639699
TI  - Estimating the relative recurrence risk ratio using a global cross-ratio model.
AB  - The relative recurrence risk ratio lambdaR (and particularly the sibling
      recurrence risk ratio, lambdaS) is often of interest to those wanting to quantify
      the genetic contribution towards risk of disease or to discriminate between
      different genetic models. However, estimating lambdaR for complex diseases for
      which genetic and environmental risk factors are both involved is not
      straightforward. Ignoring environmental factors may lead to inflated estimates of
      lambdaR. We present a marginal model which uses a copula function to model the
      association in cumulative incidence rates between pairs of relatives. This model
      is applicable to present-state data and allows estimation of risk of disease in a
      pair of relatives (and hence lambdaR), given measured environmental covariates.
      We apply the model to leprosy among sibling pairs from the Karonga district,
      Malawi. If risk factors are ignored, the apparent lambdaS in this population is
      over 3. Accounting for known nongenetic risk factors reduces it to just under 2.

PMID- 14639700
TI  - Adjustment for competing risk in kin-cohort estimation.
AB  - Kin-cohort design can be used to study the effect of a genetic mutation on the
      risk of multiple events, using the same study. In this design, the outcome data
      consist of the event history of the relatives of a sample of genotyped subjects.
      Existing methods for kin-cohort estimation allow estimation of the risk of one
      event at a time with the assumption that the censoring events are unrelated to
      the genetic mutation under study. These methods, however, may produce biased
      estimates of risk when multiple events are related to the genetic mutation, and
      follow-up of some of the events may be censored by the onset of other events.
      Using a competing risk framework to address this problem, we show that cause
      specific hazard functions for carriers and noncarriers are identifiable from kin
      cohort data. For estimation, we propose an extension of a composite-likelihood
      approach we described previously. We illustrate the use of the proposed method
      for estimation of the risk of ovarian cancer from BRCA1/2 mutations in the
      absence of breast cancer, based on data from the Washington Ashkenazi Kin-Cohort
      Study. We also evaluate the performance of the proposed estimation method, based
      on simulated data that were generated following the setup of the Washington
      Ashkenazi Study.

PMID- 14639701
TI  - Score tests for epistasis models on quantitative traits using general pedigree
      data.
AB  - Efficient score tests for a two-locus model for quantitative traits are proposed
      for general pedigrees. Two search strategies, simultaneous search and conditional
      search, are considered. These tests are attractive alternatives to the likelihood
      ratio test for their asymptotic equivalency to their respective likelihood ratio
      tests and efficiency in computation. The finite-sample properties of these tests
      are investigated through simulations. Extensions to more complicated models and
      to other search strategies are discussed.

PMID- 14639702
TI  - Candidate gene association analysis for a quantitative trait, using parent
      offspring trios.
AB  - With the increasing availability of genetic data, many studies of quantitative
      traits focus on hypotheses related to candidate genes, and also gene-environment
      (G x E) and gene-gene (G x G) interactions. In a population-based sample,
      estimates and tests of candidate gene effects can be biased by ethnic
      confounding, also known as population stratification bias. This paper
      demonstrates that even a modest degree of ethnic confounding can lead to
      unacceptably high type I error rates for tests of genetic effects. The parent
      offspring trio design is reviewed, and several forms of the quantitative
      transmission disequilibrium test (QTDT) are summarized. A variation of the QTDT
      (QTDTM) is described that is based on a linear regression model with multiple
      intercepts, one per parental mating type. This and other models are expanded to
      allow testing of G x E and G x G interactions. A method for computing required
      sample sizes using direct computations is described. Sample size requirements for
      tests of genetic main effects and G x E and G x G interactions are compared
      across various QTDT approaches to infer their efficiencies relative to one
      another. The QTDTM is found to meet or exceed the efficiency of other QTDT
      approaches. For example, the QTDTM is approximately 3% more efficient than the
      QTDT of Rabinowitz ([1997] Hum. Hered. 47:342-350) for testing a genetic main
      effect, but can be as much as twice as efficient for testing G x E interaction,
      and three times more efficient for testing G x G interaction.

PMID- 14639703
TI  - Reducing sample sizes in genome scans: group sequential study designs with
      futility stops.
AB  - Group sequential study designs can greatly facilitate analyses of genetic linkage
      in complex traits. We recently proposed designs allowing stopping investigations
      early if the result is significant (Konig et al. [2001] Am. J. Hum. Genet. 69:590
      600), thereby decreasing average sample sizes under the alternative hypothesis.
      However, average sample sizes were slightly increased under the null hypothesis.
      We now present designs where the analysis of markers is additionally stopped in
      case of futility, i.e., if the probability for significant results is
      sufficiently low. These sequential designs are applied to linkage analyses of
      single loci. We calculated sample sizes, time points, and critical boundaries for
      all analyses for 2- and 3-stage designs at an overall significance level of
      0.0001. To confirm the validity of asymptotic approximations, Monte Carlo
      simulations were performed. The utility is demonstrated analyzing genome scan
      data provided for the Genetic Analysis Workshop 12. Application of the novel
      sequential designs yields tremendous decreases in average sample sizes,
      regardless of the size of the underlying genetic effect at investigated loci.
      Depending on the applied design, almost half of the sample size is spared on
      average. These enormous savings are expected to have a special impact on costs
      and time of large-scale studies such as genome scans.

PMID- 14639704
TI  - Sum statistics for the joint detection of multiple disease loci in case-control
      association studies with SNP markers.
AB  - In complex traits, multiple disease loci presumably interact to produce the
      disease. For this reason, even with high-resolution single nucleotide
      polymorphism (SNP) marker maps, it has been difficult to map susceptibility loci
      by conventional locus-by-locus methods. Fine mapping strategies are needed that
      allow for the simultaneous detection of interacting disease loci while handling
      large numbers of densely spaced markers. For this purpose, sum statistics were
      recently proposed as a first-stage analysis method for case-control association
      studies with SNPs. Via sums of single-marker statistics, information over
      multiple disease-associated markers is combined and, with a global significance
      value alpha, a small set of "interesting" markers is selected for further
      analysis. Here, the statistical properties of such approaches are examined by
      computer simulation. It is shown that sum statistics can often be successfully
      applied when marker-by-marker approaches fail to detect association. Compared
      with Bonferroni or False Discovery Rate (FDR) procedures, sum statistics have
      greater power, and more disease loci can be detected. However, in studies with
      tightly linked markers, simple sum statistics can be suboptimal, since the
      intermarker correlation is ignored. A method is presented that takes the
      correlation structure among marker loci into account when marker statistics are
      combined.

PMID- 14639705
TI  - Rank truncated product of P-values, with application to genomewide association
      scans.
AB  - Large exploratory studies are often characterized by a preponderance of true null
      hypotheses, with a small though multiple number of false hypotheses. Traditional
      multiple-test adjustments consider either each hypothesis separately, or all
      hypotheses simultaneously, but it may be more desirable to consider the combined
      evidence for subsets of hypotheses, in order to reduce the number of hypotheses
      to a manageable size. Previously, Zaykin et al. ([2002] Genet. Epidemiol. 22:170
      185) proposed forming the product of all P-values at less than a preset
      threshold, in order to combine evidence from all significant tests. Here we
      consider a complementary strategy: form the product of the K most significant P
      values. This has certain advantages for genomewide association scans: K can be
      chosen on the basis of a hypothesised disease model, and is independent of sample
      size. Furthermore, the alternative hypothesis corresponds more closely to the
      experimental situation where all loci have fixed effects. We give the
      distribution of the rank truncated product and suggest some methods to account
      for correlated tests in genomewide scans. We show that, under realistic
      scenarios, it provides increased power to detect genomewide association, while
      identifying a candidate set of good quality and fixed size for follow-up studies.

PMID- 14639706
TI  - Cleft palate, transforming growth factor alpha gene variants, and maternal
      exposures: assessing gene-environment interactions in case-parent triads.
AB  - We have previously reported a threefold risk of cleft palate only (CPO) among
      children homozygous for the less common allele A2 at the TaqI marker site of the
      transforming growth factor alpha gene (TGFA) (Jugessur et al. [2003a] Genet.
      Epidemiol. 24:230-239). Here we assess possible interaction between the child's
      TGFA TaqI A2A2 genotype and maternal cigarette smoking, alcohol consumption, use
      of multivitamins and folic acid. This was done by comparing the strength of
      genetic associations between strata of exposed and unexposed case-parent triads.
      We also looked for possible gene-gene interaction with the polymorphic variant
      C677T of the folic acid-metabolizing gene MTHFR. We analyzed a total of 88
      complete CPO triads selected from a population-based study of orofacial clefts in
      Norway (May 1996-1998). No evidence of interaction was observed with either
      smoking or alcohol use. The risk associated with two copies of the A2 allele at
      TGFA TaqI was strong among children whose mothers did not use folic acid
      (relative risk=4.5, 95% confidence interval=1.3-15.7), and was only marginal
      among children whose mothers reported using folic acid (RR=1.4, 95% CI=0.2-12.7).
      Although the interaction between the child's genotypes at TGFA TaqI and MTHFR
      C677T was not statistically significant, the effect of the TGFA TaqI A2A2
      genotype appeared to be stronger among children with either one or two copies of
      the T-allele at C677T (RR=4.0, 95% CI=1.1-13.9) compared to children homozygous
      for the C-allele (RR=1.7, 95% CI=0.2-15.7). In conclusion, we find little
      evidence of interaction between the child's genotypes at TGFA TaqI and various
      exposures for cleft palate, with the possible exception of folic acid intake.

PMID- 14639707
TI  - Heritability of LDL peak particle diameter in the Quebec Family Study.
AB  - LDL size has been associated with the risk of coronary heart disease. The
      objective of the present study was to verify whether familial factors influence
      LDL peak particle diameter (LDL-PPD), a quantitative trait reflecting the size of
      the major LDL subclass. LDL-PPD was measured by 2-16% polyacrylamide gradient gel
      electrophoresis in 681 members of 236 nuclear families participating in the
      Quebec Family Study. LDL-PPD was adjusted for age (LDL-PPD1), age and body mass
      index (LDL-PPD2), or age, body mass index, and plasma triglyceride levels (LDL
      PPD3) separately in men and women. The residual scores were used to test for
      familial aggregation, using an ANOVA and to compute maximum likelihood estimates
      of familial correlations. The ANOVA test revealed that family lines accounted for
      47.4%, 46.7%, and 48.9% of the variance in the LDL-PPD1, LDL-PPD2, and LDL-PPD3
      phenotypes, respectively. The pattern of familial correlations revealed no
      significant spouse correlations but significant parent-offspring and sibling
      correlations for the three LDL-PPD phenotypes, with maximal heritability
      estimates of 59%, 58%, and 52% for LDL-PPD1, LDL-PPD2, and LDL-PPD3,
      respectively. These results suggest that LDL-PPD strongly aggregates in families,
      and that the familial resemblance appears to be primarily attributable to genetic
      factors. Genes responsible for this genetic contribution remain to be identified.

PMID- 14639708
TI  - Model comparison and the likelihood ratio test in segregation analysis.

PMID- 14639709
TI  - Haplotyping using SIMPLE: caution on ignoring interference.

PMID- 14639710
TI  - Parameter estimation in ascertainment adjustment in complex diseases.

PMID- 14639716
TI  - From amorphous to crystalline by design: bio-inspired fabrication of large
      micropatterned single crystals.

PMID- 14639717
TI  - Atomic layer deposition chemistry: recent developments and future challenges.
AB  - New materials, namely high-k (high-permittivity) dielectrics to replace SiO(2),
      Cu to replace Al, and barrier materials for Cu, are revolutionizing modern
      integrated circuits. These materials must be deposited as very thin films on
      structured surfaces. The self-limiting growth mechanism characteristic to atomic
      layer deposition (ALD) facilitates the control of film thickness at the atomic
      level and allows deposition on large and complex surfaces. These features make
      ALD a very promising technique for future integrated circuits. Recent ALD
      research has mainly focused on materials required in microelectronics. Chemistry,
      in particular the selection of suitable precursor combinations, is the key issue
      in ALD; many interesting results have been obtained by smart chemistry. ALD is
      also likely to find applications in other areas, such as magnetic recording
      heads, optics, demanding protective coatings, and micro-electromechanical
      systems, provided that cost-effective processes can be found for the materials
      required.

PMID- 14639718
TI  - Strained heterocycles in radical chemistry.
AB  - Over the last few decades the use of radicals in synthesis has witnessed an
      explosive growth through introduction of efficient chain and electron-transfer
      reactions. Strained heterocycles, in particular, have emerged as a highly
      versatile and readily available class of radical precursors. The generation of
      carbinyl radicals of heterocycles has resulted in many elegant applications of
      heteroatom-centered radicals, such as beta fragmentations, cyclizations, and
      intramolecular hydrogen atom abstractions. Direct electron transfer to strained
      heterocycles has been realized through the use of arene radical anions. The
      method combines the virtues of radical and organometallic chemistry to yield
      useful functionalized organolithium compounds. Epoxides have been opened with
      high regioselectivity by titanocene(III) reagents in either stoichiometric or
      catalytic quantities to yield beta-titanoxy radicals. This development has
      resulted in many new applications in natural product synthesis.

PMID- 14639719
TI  - Nanoparticle nanotubes.

PMID- 14639720
TI  - Self-assembled microarrays of attoliter molecular vessels.

PMID- 14639721
TI  - Immobilization of natural products on glass slides by using a photoaffinity
      reaction and the detection of protein-small-molecule interactions.

PMID- 14639722
TI  - Temperature-dependent interconversion of an anthracene radical cation/electron
      moiety to an electron-hole pair in the pores of Al-ZSM-5 zeolites.

PMID- 14639723
TI  - Flux closure in self-assembled cobalt nanoparticle rings.

PMID- 14639724
TI  - Ligand and metal effects on the formation of main-group polyhedral clusters.

PMID- 14639725
TI  - Complexation of carbon nanorings with fullerenes: supramolecular dynamics and
      structural tuning for a fullerene sensor.

PMID- 14639726
TI  - Facile fabrication of inorganic-polymer core-shell nanostructures by a one-step
      vapor deposition polymerization.

PMID- 14639727
TI  - Self-assembling peptide polyelectrolyte beta-sheet complexes form nematic
      hydrogels.

PMID- 14639728
TI  - Aluminoborate-based molecular sieves with 18-octahedral-atom tunnels.

PMID- 14639729
TI  - Ruthenium-stabilized low-coordinate phosphorus atoms: structural evidence for
      monomeric metaphosphonate.

PMID- 14639730
TI  - Base-induced condensation of alpha-chloro oxime derivatives furnishes alkynes.

PMID- 14639731
TI  - Highly selective synthesis of enamines from olefins.

PMID- 14639732
TI  - Multicomponent porphyrin assemblies as functional bidentate phosphite ligands for
      regioselective rhodium-catalyzed hydroformylation.

PMID- 14639733
TI  - Catalytic dihydroxylation of olefins with hydrogen peroxide: an organic-solvent-
      and metal-free system.

PMID- 14639734
TI  - Studies directed toward the total synthesis of lactonamycin: control of the sense
      of cycloaddition of a quinone through directed intramolecular catalysis.

PMID- 14639735
TI  - Total synthesis of lactonamycinone.

PMID- 14639736
TI  - Affinity-based tagging of protein families with reversible inhibitors: a concept
      for functional proteomics.

PMID- 14639737
TI  - [3,3] Sigmatropic rearrangement of boron-containing allyl alcohols: synthesis of
      allyl addition reagents.

PMID- 14639738
TI  - A versatile metathesis reaction for the formation of labile bonds between group
      13 and group 15 atoms.

PMID- 14639741
TI  - Synthesis and antibacterial activities of 4-pyrrolidinylthio carbapenems:
      containing heteroaromatics as a side chain.
AB  - The synthesis of a new series of 2-alkyl-4-pyrrolidinylthio-b-methylcarbapenems
      containing the substituted heteroaromatic moieties is described. Their in vitro
      antibacterial activities against both gram-positive and gram-negative bacteria
      were tested. The effect of substituents on the nitrogen atoms at heteroaromatic
      rings was investigated. Particular compounds (14 b, 14 c) containing 3-methyl-
      and 3, 5-dimethylpyrazolethio substituted moiety showed the most potent
      antibacterial activity.

PMID- 14639742
TI  - Synthesis and antibacterial activity of 1 beta-methyl-2-(5-substituted
      imidazolino pyrrolidin-3-ylthio)carbapenem derivatives.
AB  - The synthesis of a new series of 1 beta-methylcarbapenems containing a
      substituted imidazolino pyrrolidine moiety is described. Their in vitro
      antibacterial activities against both Gram-positive and Gram-negative bacteria
      were tested and the effect of the substituent on the imidazoline ring was
      investigated. Compound 13 g which has a N-sulfonylmethyl substituted imidazoline
      moiety showed the most potent antibacterial activity.

PMID- 14639743
TI  - Synthesis and structure-activity relationship of di-(3, 8
      diazabicyclo[3.2.1]octane) diquaternary ammonium salts as unique analgesics.
AB  - Based on the structure characteristics of the lead compounds, 1, 1' octanedioyl
      4, 4'-dimethyl-4, 4'-dibenzyl dipiperazinium dibromide (2) and 3, 8-disubstituted
      3, 8-diazabicyclo [3.2.1]octanes (DBO), di-(3, 8-diazabicyclo [3.2.1]octane)
      diquaternary ammonium salts 3 a-c were designed and synthesized through a highly
      practical procedure. Target compounds 3 a-c and the hydrochloride salts of their
      precursors 10 a-c were evaluated for their in vivo analgesic and sedative
      activities. Interestingly, the introduction of an endoethylenic bridge in the
      piperazine of lead compound 2 causes loss of the analgesic activity and increases
      the toxicity dramatically. This result shows that the flexible conformation of
      piperazine in compound 2 is favorable for interaction with the receptor, and the
      quaternization of compounds 10 a-c is the main reason for the toxicity increase.

PMID- 14639744
TI  - D2 dopaminergic and 5-HT1A serotonergic activity of 2-(1-naphthyl)ethyl- and 2-(2
      naphthyl)ethyl amines.
AB  - Several tertiary 2-phenylethyl, 2-(1-naphthyl)ethyl and 2-(2-naphthyl)ethyl
      amines were synthesized and their binding affinities for dopamine D(1), D(2) and
      serotonin 5-HT(1A) receptors evaluated in radioligand binding assays. All
      compounds were inactive in D(1) dopamine radioligand binding assay. The 2-(1
      naphthyl)ethyl analogues expressed a low but significant binding affinity for the
      D(2) and moderate one for the 5-HT(1A) receptor subtypes. Most of the remaining
      compounds expressed binding affinity at the 5-HT(1A) receptor subtype but were
      inactive in D(2) receptor binding assay. Based on these results and considering
      the chemical characteristics of the compounds synthesized and evaluated for
      dopaminergic and serotonergic activity throughout the present study it can be
      concluded that hydrophobic type of interaction (stacking or edge-to-face) plays a
      significant role in the formation of receptor-ligand complexes of 2-(1
      naphthyl)ethyl amines. This structural motive can be applied to design and
      synthesize new, more potent dopaminergic/serotonergic ligands by slight chemical
      modifications.

PMID- 14639745
TI  - Synthesis, biological activity, and docking studies of new acetylcholinesterase
      inhibitors of the bispyridinium type.
AB  - A novel series of acetylcholinesterase (AChE) inhibitors of the bispyridinium
      type was synthesized and the inhibitory activity against AChE and
      butyrylcholinesterase (BChE) measured. In essence, the substitution pattern
      influenced the inhibitory potency against AChE, where the most active
      bispyridiniumoxime (TMB-4) was bisbenzyl substituted followed by monobenzyl
      substituted, bismethyl substituted, and unsubstituted derivatives of TMB-4.
      Hence, the bisbenzyl ether of TMB-4 was further investigated. In order to obtain
      diverse lipophilic and electronic properties for these bisbenzyl bispyridinium
      derivatives (so-called DUO series), the lateral ring substitution was
      systematically varied. The lowest IC(50) value against AChE found thus far in the
      DUO series was 0.34 microM. Docking studies were carried out to elucidate the
      differences in biological activity. A general binding mode for nearly all
      compounds could be identified by these investigations. In this binding mode, the
      docked ligands span the narrow, deeply buried active-site gorge, interacting with
      Trp84 at the bottom of the gorge, Tyr334 or Phe331 halfway down the gorge, and
      Trp279 at the peripheral anionic site at the mouth of the gorge. For specific
      ligands, additional interactions were found which helped to explain their
      deviating activity. Based on the promising characteristics of the novel
      acetylcholinesterase inhibitors presented, a series of structurally related,
      optimized candidates will be developed.

PMID- 14639746
TI  - Improved piecewise orthogonal signal correction algorithm.
AB  - Piecewise orthogonal signal correction (POSC), an algorithm that performs local
      orthogonal filtering, was recently developed to process spectral signals. POSC
      was shown to improve partial leastsquares regression models over models built
      with conventional OSC. However, rank deficiencies within the POSC algorithm lead
      to artifacts in the filtered spectra when removing two or more POSC components.
      Thus, an updated OSC algorithm for use with the piecewise procedure is reported.
      It will be demonstrated how the mathematics of this updated OSC algorithm were
      derived from the previous version and why some OSC versions may not be as
      appropriate to use with the piecewise modeling procedure as the algorithm
      reported here.

PMID- 14639747
TI  - Laser-induced breakdown spectroscopy detection and classification of biological
      aerosols.
AB  - Laser-induced breakdown spectroscopy (LIBS) is examined as a potential method for
      detecting airborne biological agents. A spectrally broadband LIBS system was used
      for laboratory measurements on some common biological agent simulants. These
      measurements were compared to those of common, naturally occurring biological
      aerosol components (pollen and fungal spores) to determine the potential of LIBS
      for discriminating biological agents from natural background aerosols. A
      principal components analysis illustrates that linear combinations of the
      detected atomic lines, which are present in different ratios in each of the
      samples tested, can be used to discriminate biological agent simulants from other
      biological matter. A more sensitive, narrowband LIBS instrument was used to
      demonstrate the detection of single simulant (Bg) particles in the size range 1-5
      microns. Ca, Mg, and Na, which are present in varying concentrations between 0.3
      and 11% (by mass) in the Bg particles, were observed in single particles using
      LIBS.

PMID- 14639748
TI  - Luminescent lanthanide chelate contrast agents and detection of lesions in the
      hamster oral cancer model.
AB  - Lanthanide chelates are a somewhat unique class of molecules that have proven to
      be useful in the biomedical field due to their extremely large Stokes' shift and
      long fluorescent lifetimes. The ability of these molecules to produce
      fluorescence in the low- or zero-back-ground regime makes this class of molecules
      excellent candidates for use as contrast agents for a wide variety of
      applications in biological settings. Here we present the preparation,
      spectroscopic characterization, and application of a new terbium chelate contrast
      agent, based on the 1,4,7,10-tetraazacyclododecane macrocycle (cyclen), for
      detection of early-stage malignant lesions in the Syrian hamster cheek pouch. Tb
      P(CTMB) delivers bright blue-green luminescence when excited with low photon
      fluxes of UV light. As a pilot study, the DMBA-treated Golden Hamster Cheek pouch
      epithelial cancer model was employed and Tb-P(CTMB) was used as a topical agent
      for the visual detection of diseased tissue. In this preliminary study the agent
      tended to associate with early-stage malignant lesions, suggesting that Tb
      P(CTMB) could be used as a contrast agent to aid in identifying early-stage oral
      cancer lesions.

PMID- 14639749
TI  - Temperature-dependent near-infrared spectra of bovine serum albumin in aqueous
      solutions: spectral analysis by principal component analysis and evolving factor
      analysis.
AB  - Fourier transform near-infrared (FT-NIR) spectra have been measured for bovine
      serum albumin (BSA) in an aqueous solution (pH 6.8) with a concentration of 5.0
      wt% over a temperature range of 45-85 degrees C. Not only conventional spectral
      analysis methods, such as second-derivative spectra and difference spectra, but
      also chemometrics, such as principal component analysis (PCA) and evolving factor
      analysis (EFA), have been employed to analyze the temperature-dependent NIR
      spectra in the 7500-5500 and 4900-4200 cm-1 regions of the BSA aqueous solution.
      Intensity changes of bands in the 7200-6600 cm-1 and 4650-4500 cm-1 regions in
      the difference spectra indicate variations of the hydration and secondary
      structure of BSA in the aqueous solution, respectively. The plot of a band
      intensity at 7080 cm-1 in the different spectra shows a clear turning point at 63
      degrees C, revealing that a significant change in the hydration occurs at about
      63 degrees C. The forward and backward eigenvalues (EVs) from EFA suggest that
      marked changes in the hydration and secondary structure of BSA take place in the
      temperature ranges of 61-65 degrees C and 59-63 degrees C, respectively. In
      addition, the temperature of 71 degrees C marked in the EFA plots may correspond
      to the onset temperature of increase in the intermolecular beta-sheet structure.

PMID- 14639750
TI  - Near-infrared spectroscopic measurement of urea in dialysate samples collected
      during hemodialysis treatments.
AB  - Single-beam spectra were collected over the combination region of the near
      infrared spectrum for 80 samples collected from 15 people over a two-week period.
      Partial least-squares (PLS) regression was used to generate an optimized
      calibration model for urea. PLS calibration models accurately measure urea in the
      spent dialysate matrix. Prediction errors are on the order of 0.15 mM, which is
      sufficient for the clinical assessment of the dialysis process. In addition, the
      feasibility of a global calibration model is demonstrated by generating a
      calibration model from samples and spectra obtained from 12 people to predict the
      level of urea in samples collected from 3 different people. In this case, the
      standard error of prediction is 0.09 mM. Spectra were modified in order to
      systematically examine the impact of resolution and noise. Little impact is
      observed by altering the spectral resolution from 4 to 32 cm-1. Spectral noise,
      however, plays an important role in the accuracy of these calibration models.
      Increasing the magnitude of the spectral noise increases the prediction errors
      and increases the width of the spectral range necessary for extracting the
      analytical information. The utility of the method is demonstrated by analyzing
      dialysate samples collected during actual dialysis treatments. In addition, the
      necessary resolution and spectral quality necessary for reliable on-line urea
      monitoring is identified. These findings indicate that a dedicated, on-line urea
      spectrometer must posses a resolution of 16 cm-1 coupled with a sample thickness
      of 1.5 mm and spectral noise levels on the order of 25 micro-absorbance units
      when measured as the root-mean-square (RMS) noise of 100% lines.

PMID- 14639751
TI  - In vivo noninvasive measurement of blood glucose by near-infrared diffuse
      reflectance spectroscopy.
AB  - This paper reports in situ noninvasive blood glucose monitoring by use of near
      infrared (NIR) diffuse-reflectance spectroscopy. The NIR spectra of the human
      forearm were measured in vivo by using a pair of source and detector optical
      fibers separated by a distance of 0.65 mm on the skin surface. This optical
      geometry enables the selective measurement of dermis tissue spectra due to the
      skin's optical properties and reduces the interference noise arising from the
      stratum corneum. Oral glucose intake experiments were performed with six subjects
      (including a single subject with type I diabetes) whose NIR skin spectra were
      measured at the forearm. Partial least-squares regression (PLSR) analysis was
      carried out and calibration equations were obtained with each subject
      individually. Without exception among the six subjects, the regression
      coefficient vectors of their calibration models were similar to each other and
      had a positive peak at around 1600 nm, corresponding to the characteristic
      absorption peak of glucose. This result indicates that there is every possibility
      of glucose detection in skin tissue using our measurement system. We also found
      that there was a good correlation between the optically predicted values and the
      directly measured values of blood samples with individual subjects. The potential
      of noninvasive blood glucose monitoring using our methodology was demonstrated by
      the present study.

PMID- 14639752
TI  - Observation of Fourier transform near-infrared vibrational circular dichroism to
      6150 cm-1.
AB  - We report here the first measurement of near-infrared (NIR) vibrational circular
      dichroism (VCD) with Fourier transform (FT) instrumentation. The measurements
      were carried out using a commercial rapid-scan FT-IR VCD spectrometer modified
      for operation in the NIR region between 3750 and 6150 cm-1. Overtone and
      combination band VCD intensities, first reported by Keiderling and Stephens using
      dispersive VCD instrumentation in 1976, were reproduced with equivalent signal
      quality and spectral resolution using collection times of only a few minutes.
      These results offer substantial promise for the routine use of rapid-scan FT
      instrumentation for the measurement of overtone and combination band VCD spectra
      in the NIR region.

PMID- 14639753
TI  - Fourier transform infrared synchrotron ellipsometry for studying the anisotropy
      of small organic samples.
AB  - An experimental setup for polarization-dependent and spectroscopic ellipsometric
      measurements was developed that utilizes the brilliance of synchrotron infrared
      radiation at the electron storage ring at BESSY II for investigations of small
      samples and sample areas. During commissioning of the beamline and the
      experimental setup, a 1 mm2 piece of a well-characterized polyimide film was
      studied to show the benefits of Fourier transform infrared (FT-IR) synchrotron
      ellipsometry. The band shapes are interpreted with respect to the anisotropic
      distribution of transition dipole moments within the film. In comparison to a
      globar source, the signal intensity has been improved by more than one order of
      magnitude for this example.

PMID- 14639754
TI  - Diffuse reflection infrared Fourier transform (DRIFT) spectra and high
      temperature DRIFT spectra of beta-Ni(IO3)2.4H2O, Ni(IO3)2.2H2O, Mg(OH)2, and
      Zn(OH)F: novel embedding materials.
AB  - Diffuse reflection infrared Fourier transform (DRIFT) spectra of the hydroxides
      Mg(OH)2 and Zn(OH)F and the iodate hydrates beta-Ni(IO3)2.4H2O and Ni(IO3)2.2H2O
      have been recorded at ambient and high temperature. Spectra without shifts of the
      band maxima compared to those of conventional infrared transmission spectra and
      without inversion of the bands were obtained by dilution of the compounds to
      about 2-10% with an appropriate embedding material. alpha-Al2O3, TiO2, ZrO2,
      PbF2, MgO, BaO, ZnO, Na2SiO3, SiO2 (aerosil), and powdered copper, aluminum, and
      magnesium were tested as diluents for hydrates and hydroxides, especially at
      elevated temperatures, as alternatives for the commonly used KBr. Thus, alpha
      Al2O3, PbF2, and powdered copper were established as the most favorable diluents.
      Using these novel embedding materials, high-temperature DRIFT spectra are
      obtainable at temperatures not accessible with KBr discs. Dehydration and
      decomposition of the iodate hydrates under study were shown by change or
      disappearance of the respective water bands.

PMID- 14639755
TI  - Increasing detectivity of polarization modulation infrared reflection-absorption
      spectroscopy for the study of ultrathin films deposited on various substrates.
AB  - In this paper, we present a simple way to increase the sensitivity of
      polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS)
      for the study of ultrathin films deposited on dielectric and semiconductor
      substrates. The enhancement of the absorption band intensity is obtained by
      reducing the signal arising from the substrate. This is achieved by adding a
      polarizer after the sample in order to balance the polarized reflectivities of
      the sample. As a consequence, the contribution of the film to the PM-IRRAS signal
      is increased relative to that of the substrate. An enhancement factor of about 10
      has been obtained for ultrathin organic films deposited on glass and spread at
      the air-water interface. This method has also allowed the study of the very thin
      native oxide layer present on silicon without the need for the reference spectrum
      of bare silicon.

PMID- 14639756
TI  - Infrared reflection-absorption spectra of metal-effect coatings.
AB  - The results of studies of infrared reflection-absorption spectra of metal-effect
      coatings are presented in this paper. Such coatings consist of metallic flakes
      that are dispersed in a polymer binder. The spectra show two distinct phenomena.
      One is due to the polymer matrix. The other is due to metallic flakes that are
      dispersed inside the layer. The polymer binder causes narrow spectral lines that
      give a thickness-dependent intensity and position. Metallic flakes change the
      average baseline of this spectrum over the entire infrared spectral region. This
      particular effect was evaluated using a simple rough-surface model. Two
      parameters of the model, the root-mean-square roughness and the correlation
      length of the rough surface, described the reflection of the partial beams on the
      metal flake surfaces and scattering on flakes boundaries. The other two
      parameters are the specular reflectance and the diffuse reflectance of the plane
      untextured interface between the polymer matrix and the metal flake surface.
      Various metal-effect coatings within the same polymer binder were analyzed. The
      effect of each metal flake dispersion was evaluated by the parameters within the
      rough-surface model. The results were analyzed in terms of the size and the
      loadings of flakes that were used in the coatings.

PMID- 14639757
TI  - Adsorption of methylene blue onto silylated silica surfaces, studied using
      visible attenuated total reflection spectroscopy with a slab optical waveguide.
AB  - The behavior of methylene blue (MB) molecules at silica/water and silylated
      silica/water interfaces was examined using visible attenuated total reflection
      spectroscopy with a slab optical waveguide (SOWG). An alkyl silane coating
      changed the adsorbed form of MB on the surface from a dimer (lambda max = 600 nm,
      bare silica surface) to a monomer (lambda max = 670 nm), and the carbon number of
      the silylation reagent influenced the amount of adsorption and the orientation of
      the molecule. Moreover, the addition of an anionic surfactant,
      dodecylbenzenesulfonate (DBS), caused the deposition of MB/DBS ion pairs, which
      gave an identical attenuated total reflection (ATR) spectrum to that of the
      dimer. Linear dichroism measurements revealed that the ion pairs were adsorbed
      onto the silylated silica surface randomly in terms of the orientation angle of
      MB, while the MB monomer was strongly oriented, i.e., the direction of the
      transition moment of MB roughly parallels the surface plane. This difference in
      the orientation angles of the adsorbed species can be utilized for their
      selective detection using polarization SOWG measurements.

PMID- 14639758
TI  - Differential thermal lensing in extended samples.
AB  - We present a new scheme for a pump-probe mode-mismatched thermal lensing
      experiment aimed at extracting the value of low-absorbing components in the
      presence of a high-absorbing background. The method allows for the use of large
      path-length samples. Changes in the background absorption of a column of ethanol
      of 20 cm of 1% and a pollutant concentration detection limit of 0.04 ppm are
      obtained when using a pump light power of 34 mW.

PMID- 14639759
TI  - Slag analysis with laser-induced breakdown spectrometry.
AB  - Laser-induced breakdown spectrometry (LIBS) has been applied for multi-elemental
      analysis of slag samples from a steel plant. In order to avoid the time-consuming
      step of sample preparation, the liquid slag material can be filled in special
      probes. After cooling of the liquid slag and solidification, the samples can be
      analyzed with LIBS. Chemical analysis of slag is an essential input parameter
      used for numerical simulations to control liquid steel processing. The relative
      variation range of element concentrations in slag samples from steel production
      can amount to up to 30%. A multivariate calibration model is used to take into
      account matrix effects caused by these varying concentrations. By optimizing the
      measuring parameters as well as the calibration models, an agreement between the
      standard X-ray fluorescence (XRF) analysis and LIBS analysis in terms of the
      coefficient of determination r2 of 0.99 for the main analytes CaO, SiO2, and
      Fetot of converter slag samples was achieved. The average repeatability of the
      LIBS measurement for these elements in terms of the relative standard deviation
      of the determined concentration is improved to less than 1.0%. With these
      results, the basis is established for future on-line applications of LIBS in the
      steel-making industry for slag analysis.

PMID- 14639760
TI  - Crystal-smectic G transformation investigated by temperature-dependent Raman
      study.
AB  - We report on a temperature-dependent Raman study of terephthalidine-bis
      butylaniline (TBBA) and terephthalidine-bis-heptylaniline (TB7A) in the
      temperature range 10-406 K and in the wavenumber regions 1120-1240 cm-1 and 1500
      1700 cm-1. The variations of peak positions and linewidths of several Raman
      marker bands with temperature, which clearly show crystal-SmG transition at
      approximately 334 K, have been used to discuss the dynamics of this phase
      transition. The temperature-dependent Raman study revealed that the increased
      vibration of the long alkyl tail and the rotation around the long molecular axis
      are the two primary phenomena responsible for the crystal-SmG transition. Density
      functional theory (DFT) at the B3LPY/6-31G(d) level was employed to obtain the
      optimized geometry and the harmonic vibrational wavenumbers of TBBA. The
      eigenvectors of the modes corresponding to these marker bands were also
      calculated.

PMID- 14639761
TI  - High-temperature and high-pressure cubic zirconia anvil cell for Raman
      spectroscopy.
AB  - A simple and inexpensive cubic zirconia anvil cell has been developed for the
      performance of in situ Raman spectroscopy up to the conditions of 500 degrees C
      and 30 kbar pressure. The design and construction of this cell are fully
      described, as well as its applications for Raman spectroscopy. Molybdenum heater
      wires wrapped around ceramic tubes encircling two cubic zirconia anvils are used
      to heat samples, and the temperatures are measured and controlled by a Pt-PtRh
      thermocouple adhered near the sample chamber and an intelligent digital control
      apparatus. With this cell, Raman spectroscopic measurements have been
      satisfactorily performed on water at 6000 bar pressure to 455 degrees C and on
      ice of room temperature to 24 kbar, in which the determinations of pressures make
      use of changes of the A1 Raman modes of quartz and the shift of the sharpline (R
      line) luminescence of ruby, respectively.

PMID- 14639762
TI  - High-pressure high-temperature Raman spectroscopy of liquid and supercritical
      fluids.

PMID- 14639764
TI  - Virtual column method for correcting masking effects in Hadamard transform
      systems.

PMID- 14639763
TI  - Single scan cosmic spike removal using the upper bound spectrum method.

PMID- 14639765
TI  - Predicted spatial resolution of super-resolving fluorescence microscopy using two
      color fluorescence dip spectroscopy.

PMID- 14639767
TI  - Are you being served? Truth, consequences and legal advice to keep you out of hot
      water.

PMID- 14639766
TI  - Is dentistry dancing with the devil?

PMID- 14639768
TI  - Exit strategy. Tax, legal and financial considerations in practice transitions.

PMID- 14639769
TI  - Caveat emptor. The IRS cracks down on shady tax shelters promoted to dentists.

PMID- 14639770
TI  - Avoid financial gridlock in a dental group. How to gain financial benefits, even
      if your partners don't.

PMID- 14639771
TI  - Unseen, untold, unsold.

PMID- 14639772
TI  - Periodontal disease: what it is and what to do about it.

PMID- 14639773
TI  - An offer we can and should refuse.

PMID- 14639775
TI  - Holistic nursing management of pain and suffering: a historical view with
      contemporary applications.
AB  - Nursing is rooted in caring for those who suffer and experience pain. As nursing
      has grown through the ages, technological advances and socioeconomic changes have
      required nurses to adapt as they continue to provide holistic, patient-centered
      care. Over the past century, nursing practice has been dominated by Western
      medical culture, resulting in a relegation of the caring-healing practices of
      nurses to the margins of healthcare delivery. Recent changes in the ontology of
      caring-healing practices are rooted in a new knowledge of complimentary
      practices. Advancements in behavioral sciences and the neurobiology of pain and
      suffering, together with an acceptance of Eastern and other healing practices,
      have enriched and enlightened our understanding of pain management. The recent
      growth of self-help and support programs has enlightened the healthcare consumer
      in choosing treatments. Contemporary clinical practice may now include methods
      that reflect the interconnectedness between the mind and body, such as
      biofeedback, healing touch, aromatherapy, progressive relaxation, meditation, and
      behavioral therapy. This article examines the historical concepts of pain and
      suffering that have influenced the approach to pain management and describes
      significant holistic methods that may be utilized by the nurse in managing pain.

PMID- 14639776
TI  - Reiki: a supportive therapy in nursing practice and self-care for nurses.
AB  - Reiki is a complementary, energy-based healing modality. It has ancient roots,
      but is uniquely suited to modern nursing practice. Reiki training offers a
      precise technique for tapping into healing energy, or ki, and transmitting it
      through touch. Reiki treatments are gently balancing and provide energy that
      supports the well-being of the recipient in a holistic and individualistic way.
      Relaxation, pain relief, physical healing, reduced emotional distress, and a
      deepened awareness of spiritual connection are among the benefits attributed to
      Reiki in anecdotes, case studies, and exploratory research, as summarized in this
      review of literature. Reiki is easily adaptable to nursing practice in a variety
      of settings, and can provide support for the practitioners of Reiki themselves,
      as well as benefiting those they treat with Reiki.

PMID- 14639777
TI  - A pilot feasibility study of the effects of touch therapy on nurses.
AB  - The White House Commission on Complementary Alternative Medicine (CAM) has
      recommended that safe and effective CAM practices be evaluated to determine their
      role in maintaining wellness and promoting health. There is little research on
      individual bodywork/energy therapies and their effects on wellness. The purpose
      of this pilot study was to assess the effect of AMMA treatments on relaxation and
      anxiety in staff nurses, and to examine themes describing the nurses'
      experiences. It was hypothesized that nurses receiving AMMA treatments would
      demonstrate reduced anxiety, as measured by a Visual Analog Scale (VAS) and
      increased relaxation, measured by physiologic parameters. The study was designed
      as a prospective, randomized, blinded clinical trial, with convenience sampling
      of 24 nurses working 12-hour shifts. While both groups demonstrated decreased
      anxiety after intervention, the experimental group consistently showed greater
      differences between pre- and post-treatment anxiety scores. The mean change in
      physiologic parameters between groups was not significant. Themes derived from a
      final interview included: importance of touch in nursing care, stress reduction,
      increased self-awareness, the need for self-care and a new understanding of the
      mind-body connection. Outcomes suggest the need for further research with a
      larger population to assess this intervention's impact on anxiety, stress, self
      care and caring relationships.

PMID- 14639778
TI  - Therapeutic play: developing humor in the nurse-patient relationship.
AB  - Although there has been considerable discussion on the therapeutic aspects of
      humor in the nurse-patient relationship, little is known about the experience of
      humor in actual nurse-patient relationships. This naturalistic study was
      conducted using grounded theory methodology with participant observation,
      utilizing in-depth interviews of participants in nurse-patient dyadic
      relationships in a suburban metropolitan New York acute care hospital. The core
      process was identified as Therapeutic Play, in which humor involves caring for
      self or another. This study offers nurses and others involved in professional
      relationships an explanation of the development of humor as an alternative
      healing-caring strategy.

PMID- 14639780
TI  - Bibliography: alternative/complementary health.

PMID- 14639779
TI  - The spirit of healing: how to develop a spiritually based personal and
      professional practice.
AB  - The idea of healing must be considered within the context of a holistic approach
      to nursing practice. The authors put forth the premise that a Spirit of Healing
      enters into the nurse-client relationship or into any care-giving situation. This
      spirit is defined as a universal energy source that is accessed through imagery,
      therapeutic touch, Reiki, and other related interventions. Case studies are
      provided as illustrations, and the authors include self-help exercises and
      related definitions to enhance understanding and practice. The authors explore
      energetic techniques to treat and prevent burnout for nurses, identify specific
      ways to practice nursing from a holistic perspective, and consider the
      possibility of transforming nursing into a change agent that will redefine the
      healthcare system.

PMID- 14639781
TI  - Milk protein modification to improve functional and biological properties.

PMID- 14639782
TI  - The nutritional significance, metabolism and toxicology of selenomethionine.
AB  - SeMet is a naturally occurring toxic amino acid but at the same time represents
      the major nutritional source of selenium for higher animals and humans. The
      ability of SeMet to be incorporated into the body proteins in place of Met
      furthermore provides a means of reversible Se storage in organs and tissues. This
      property is not shared by any other naturally occurring selenoamino acid and thus
      could be associated with a specific physiological function of SeMet. Since higher
      animals cannot synthesize SeMet, yet from it all needed forms of Se are produced,
      SeMet meets the criteria of an essential amino acid. Accordingly, SeMet, or
      enriched food sources thereof, are appropriate forms of Se for human nutritional
      Se supplementation. However, while SeMet or Se yeast are already widely used in
      over-the-counter nutritional supplements, infant formulas and parenteral feeding
      mixtures still contain Se in the form of sodium selenate or sodium selenite, even
      though these are not the normal nutritional forms of Se. In animal nutrition,
      these inorganic selenium salts are increasingly replaced by food sources of SeMet
      such as Se yeast. Synthetic SeMet could also be employed as a feed additive, but
      its regulatory status is as yet undetermined. The optimal nutritional levels of
      SeMet for different animal species still need to be determined. The expectation
      is that lower additions to feedstock of equivalent levels of SeMet will suffice
      to achieve adequacy than currently approved maximum levels of Se in the form of
      inorganic Se salts.

PMID- 14639783
TI  - Echinacea as a functional food ingredient.

PMID- 14639784
TI  - Bioactive peptides and proteins.

PMID- 14639785
TI  - Plant products with hypocholesterolemic potentials.

PMID- 14639786
TI  - Smoothing OR schedule can ease capacity crunches, researchers say.

PMID- 14639787
TI  - Blackout, Isabel offer lessons in preparing for emergencies.

PMID- 14639788
TI  - Hospital moves to smooth surgery schedule.

PMID- 14639789
TI  - Advice on bargaining with anesthesia groups.

PMID- 14639790
TI  - Residents' work limits challenge staffing.

PMID- 14639791
TI  - Is new ozone sterilizer right for your OR?

PMID- 14639792
TI  - Advice on postop nausea and vomiting.

PMID- 14639793
TI  - If morale dips at your center, try FISH!

PMID- 14639794
TI  - Relationship between soup consumption, folate, beta-carotene, and vitamin C
      status in a French adult population.
AB  - The relationship between soup consumption and folic acid, beta-carotene, and
      vitamin E and C status was assessed in adults who regularly consumed soup
      compared to those who did not or who were occasional eaters. Data were obtained
      for 2114 men and 2874 women living in France and participating in the SU.VI.MAX
      cohort, who reported twelve 24-hour dietary records during a two-year follow-up
      period. Six-point-seven percent of women and 8.7% of men were heavy consumers of
      soup (i.e., they consumed soup from 9-12 days out of 12 days). Respectively, 46
      and 42.5% were regular soup consumers (3-8 days out of 12), and 47.3 and 48.8%
      were occasional or non-soup consumers (0-2 days or less out of 12). Total energy
      intake did not differ between soup consumers and non-consumers. In both genders,
      heavy consumers of soups had significantly higher intakes of carbohydrates and
      lower lipid intakes. Heavy consumers of soup had higher dietary intakes of
      folates, beta-carotene, vitamin C and, in men, of vitamin E. In heavy consumers,
      soups contributed 12.5% of total dietary intake of beta-carotene in men and 13%
      in women. For vitamin C, vitamin E, and folates, soups contributed to 4-5% of
      total vitamin intake. In heavy soup consumers, mean serum vitamin C levels were
      higher, but not significantly, than in occasional or non-soup consumers. This
      trend was also observed for red blood cell folate in women only. The present data
      suggest that consumption of soup may be beneficial in promotional programs to
      increase vegetable consumption, and may contribute to a balanced diet and a
      healthy nutritional status, and especially vitamin status, in the overall
      population.

PMID- 14639795
TI  - Plasma levels of retinol, carotenoids, and tocopherols in relation to dietary
      pattern among pregnant Tanzanian women.
AB  - In Tanzania, as in other developing countries, dietary intake of nutrients in
      pregnant women is marginal or lower than the recommended intakes and therefore
      these women are at high risk for deficiencies. Our aim was to evaluate the
      relationship between diet and plasma levels of retinol, carotenoids, and alpha
      tocopherol in the third trimester of pregnancy. Ninety pregnant women aged
      between 18 and 45 years were equally recruited from three villages. Seven-day
      food frequency data was collected by questionnaire. Plasma levels of retinol,
      carotenoids, and tocopherols were assessed by high-performance liquid
      chromatography (HPLC). Results indicated that cooked green leafy vegetables
      constituted the major source of provitamin A carotenoids, with low intake of
      yellow/orange fruits and preformed vitamin A. Lutein, lycopene, and beta-carotene
      were the predominant carotenoids in the plasma with mean values of 1.61, 0.84,
      and 0.63 mumol/L, respectively. There was no significant correlation between
      frequencies of vegetable consumption and either plasma retinol or carotenoids.
      However, increased consumption of green leafy vegetables with oil, which
      increases bioavailability, was correlated with high plasma retinol levels (p =
      0.03). Low retinol levels (< or = 0.70 mumol/L) were present in 26% of women. The
      mean plasma retinol concentration was 0.89 mumol/L and 63% of the women had
      values below 1.05 mumol/L. The mean plasma alpha-tocopherol concentration was
      15.4 mumol/L and women with plasma retinol concentration > 1.05 mumol/L had
      significantly higher mean alpha-tocopherol than women with plasma retinol
      concentration < or = 0.70 mumol/L (p < or = 0.01). Twenty-four percent of the
      women were anemic (hemoglobin: Hb < 110 g/L) and the mean Hb value was 116.3 g/L.

PMID- 14639796
TI  - Trends in dietary intake of vitamins A, C, and E in German children and
      adolescents--results of the DONALD Study.
AB  - Intake of vitamins A, C, and E was evaluated and age and time trends were
      assessed on the basis of 3-day weighed dietary records (n = 5121) of 2- to 18
      year old boys (n = 417) and girls (n = 425) enrolled in the DONALD Study
      (Dortmund Nutritional and Anthropometric Longitudinally Designed Study) 1986
      2001. Intake of vitamin A remains stable over time, intake of vitamin C increases
      linearly, and intake of vitamin E follows a nonlinear trend. Age trends of
      vitamins A and C (per MJ) were nonlinear with a minimum at the beginning
      adolescence, while intake of vitamin E (per MJ) increased linearly. Girls had
      higher nutrient densities but lower intakes expressed as percent of reference
      values. Fortified food in total had a higher impact on time trends of nutrient
      intake than other single food groups defined here. Our results point to the
      impact of the food industry on long-term nutrient intake, but also underline the
      necessity of nutrition education even in young age groups to improve vitamin
      intake.

PMID- 14639797
TI  - Umbilical serum insulin-like growth factor 1 (IGF-1) in newborns: effects of
      gestational age, postnatal age, and nutrition.
AB  - AIM: The aim of this study was to determine the relationship between nutrition,
      gestational age, and birth weight, and serum insulin-like growth factor 1 (IGF-1)
      levels in newborns. METHOD: The first study group consisted of sixty newborns:
      thirty were fed with human breast milk and the others were fed with infant
      formula. Serum samples were obtained from all the newborns on days one and seven
      of life. Seventy-two pregnant women and their neonatal cord blood serum samples
      were obtained in a labor ward in the study group. All the serum samples were
      analyzed for IGF-1 by immunoassay. RESULT: Newborns fed with human milk had
      higher serum IGF-1 concentrations compared to formula-fed controls (p < 0.05).
      Cord IGF-1 levels showed a negative correlation with birthweight (p < 0.05) and a
      positive correlation with gestational age (p < 0.05). CONCLUSION: These findings
      suggest that IGF-1 levels during the neonatal period are influenced by
      gestational age, birth weight, and nutrition.

PMID- 14639798
TI  - Severe iodine deficiency in southern Albania.
AB  - Albania does not yet have a national program for control of iodine deficiency and
      there are no recent data on the severity of the iodine deficiency disorders (IDD)
      in the country. The aim of the present study was to assess current IDD status in
      southern Albania. In primary school children in urban and rural areas urinary
      iodine concentration (UI) and iodine concentration in salt at retail and
      household levels was measured. Goiter was graded by palpation and thyroid volume
      determined by ultrasound. Children aged 5-14 yr (n = 826) were sampled at 2 urban
      and 5 rural primary schools. In the 2 urban schools, the median UI was 45
      micrograms/L, the goiter prevalence was 32%, and salt iodine levels were
      inadequate (< 15 micrograms/g) in 78% of household salt samples. In the rural
      schools, the median UI was 17 micrograms/L, the goiter prevalence was 95%, and no
      household salt samples were adequately iodized. Among children in the rural
      schools, 73% had grade 2 goiter and 20% had nodular changes detected by thyroid
      ultrasound. In southern Albania, school children in urban areas are moderately
      iodine deficient and those in rural villages are severely iodine deficient. These
      findings suggest that regional distribution of oral iodized oil capsules is
      indicated to control IDD in vulnerable groups until salt iodization is
      implemented.

PMID- 14639799
TI  - Role of dietary vitamin E in cadmium-induced oxidative damage in rabbit's blood,
      liver and kidneys.
AB  - The aim of this work was to determine the effect of dietary vitamin E intake on
      lipid peroxidation (LPO) by measuring thiobarbituric acid reactive substances
      (TBARS), vitamin E and reduced glutathione (GSH) levels, and glutathione
      peroxidase (GSH-Px: EC 1.11.1.9) activity in plasma, red blood cells (RBC),
      livers, and kidneys of rabbits dosed with cadmium (Cd). Six-month-old clinically
      healthy New Zealand White rabbits (8 in each group) were given tap water only,
      containing 1 g CdCl2/L, or tap water with CdCl2 plus vitamin E (100 mg dl-alpha
      tocopheryl acetate in 0.2 mL corn oil) daily for 30 days. The vitamin E level in
      the plasma, liver, and kidneys was significantly higher in the control than in
      the Cd-only group, and TBARS levels were significantly lower. There were no
      statistical differences between the control and Cd-only groups GSH-Px activities
      and GSH levels in RBC, liver, and kidneys. Vitamin E levels in plasma, liver, and
      kidneys and GSH-Px activity in RBC were higher in the vitamin E group than in
      both control and Cd-only groups. However, the TBARS levels of RBC, liver, and
      kidneys in vitamin E administered group were decreased. Therefore, the present
      study demonstrates the effectiveness of vitamin E in reducing oxidative stress in
      Cd-treated rabbits and suggests that reductions in increased TBARS due to Cd
      toxicity may be an important factor in the action of vitamin E.

PMID- 14639800
TI  - Lipid responses in mildly hypertriglyceridemic men and women to consumption of
      docosahexaenoic acid-enriched eggs.
AB  - This randomized, double-blind, controlled clinical trial assessed lipid responses
      in mildly hyper-triglyceridemic men and women to consumption of docosahexaenoic
      acid (DHA)-enriched eggs or ordinary chicken eggs. The study included 153
      subjects aged 21-80 years, with serum triglyceride concentrations between 140 and
      450 mg/dL, inclusive, and serum total cholesterol concentrations < 300 mg/dL.
      Subjects were randomly assigned to receive either DHA-enriched (147 mg DHA/egg)
      or ordinary eggs (20 mg DHA/egg), added to their usual diets for six weeks (10
      eggs/week). Both treatments significantly lowered triglycerides and increased
      high-density lipoprotein (HDL) cholesterol levels from baseline; however, these
      changes were not significantly different between treatments. Low-density
      lipoprotein (LDL) cholesterol concentrations increased significantly in subjects
      who consumed DHA-enriched eggs (p = 0.047 vs. control). This increase was
      significantly higher than that observed with ordinary eggs. However, there was no
      significant increase in cholesterol carried by small, dense LDL particles, as
      determined by nuclear magnetic resonance analysis. Results of exploratory
      analyses suggest favorable effects of the DHA-enriched eggs over ordinary eggs on
      triglyceride and HDL cholesterol levels in subjects with body mass index > or =
      30 kg/m2; the DHA treatment produced a larger reduction in serum triglyceride
      concentration vs. ordinary eggs (-12.3 vs. 2.1%; p = 0.027), and there was a
      greater increase for HDL cholesterol in the DHA-enriched vs. ordinary egg group
      (5.0 vs. 1.1%; p = 0.040).

PMID- 14639801
TI  - Suppressive effect of viscous dietary fiber on elevations of uric acid in serum
      and urine induced by dietary RNA in rats is associated with strength of
      viscosity.
AB  - This study was performed to clarify how dietary fiber (DF) with different
      viscosities would be associated with dietary RNA metabolism. Male Wistar strain
      rats, four weeks old, were fed diets containing a 3% (w/w) yeast RNA and a 5%
      (w/w) viscous DF for five days. Viscosity of DF samples used, in order of
      strength, were xanthan gum (XG) > guar gum (GG) > locust bean gum (LBG) > karaya
      gum (KG) > pectin (PE) = arabic gum (AG) > CM-cellulose (CMC) = inulin (IN). The
      serum uric acid concentration in the viscous DF groups significantly decreased as
      compared with that in the cellulose (CL) group. The urinary excretions of uric
      acid and allantoin in the respective groups given AG, GG, IN, KG, PE, and XG were
      significantly suppressed as compared with those in the CL group. The fecal RNA
      excretion was markedly increased in the IN, KG, PE, and XG groups in comparison
      to the CL group. The DF with high viscosity significantly suppressed RNA
      digestion by RNase A and decreased uptakes of 14C-labeled adenosine and adenosine
      5'-monophosphate (5'-AMP) in rat jejunum. The results reveal that the suppressive
      effect of DF on elevation of serum uric acid concentration induced by dietary RNA
      in rats is associated with the strength of DF viscosity. The mechanism by which
      this is accomplished is suggested to be attributed to the inhibitions of
      digestion for dietary RNA and/or absorption of the hydrolyzed compounds.

PMID- 14639802
TI  - Influence of long-chain polyunsaturated fatty acid formula feeds on vitamin E
      status in preterm infants.
AB  - It has been recommended to supplement formulas for preterm infants with n-3 and n
      6 long-chain polyunsaturated fatty acids (LCP) to improve growth, visual acuity,
      and neurodevelopmental performance. However, large amounts of LCP may increase
      lipid peroxidation and oxidative stress in preterm infants. We investigated if,
      under high supplementation of natural tocopherols, LCP addition to formula can be
      performed safely without causing tocopherol depletion in cell membranes. Thirty
      one healthy preterm infants with gestational ages from 28 to 32 weeks were
      evaluated in a prospective, randomized study from birth to day 42. Nine infants
      received an n-3 and n-6 LCP-enriched formula (A), eleven infants a standard
      formula (B), and eleven infants breast milk (control group). Alpha- and gamma
      tocopherol extracts were added to both formulas, amounting to five times the
      value in breast milk (2.3 mg/dL in both formulas versus 0.45 mg/dL in breast
      milk). Erythrocyte arachidonic acid (AA) and docosahexaenoic acid (DHA) in the
      phosphatidylethanolamine fraction were similar in the three groups over the study
      period, whereas a significant reduction of erythrocyte AA and DHA could be
      detected in the phosphatidylcholine fraction in all three groups from day 14
      onwards, when compared to respective cord blood values, with lowest values in the
      standard formula group. Amazingly, levels of alpha- and gamma-tocopherol were
      higher in plasma, erythrocytes, platelets, monocytes, and polymorphonuclear
      leukocytes with LCP supplementation as compared to standard formula and breast
      milk from day 7 onwards, whereas in buccal mucosal cells, this was not the case
      until day 42. Gammatocopherol uptake in the LCP-supplemented group was also
      significantly higher in all cell fractions studied from day 7 onwards. We
      therefore hypothesize that the LCP supplementation used in formula A improves
      tocopherol solubility and stability in biological membranes. Under high-dose
      vitamin E addition to n-3 and n-6 LCP-supplemented formula, no evidence for
      tocopherol depletion and furthermore, high accumulation of tocopherols, can be
      detected in healthy preterm infants.

PMID- 14639804
TI  - 'Sanguis naturalis' and 'sanc de miracle': ancient medicine, 'superstition' and
      the metaphysics of mediaeval healing miracles.

PMID- 14639803
TI  - Effects of lifestyle modification and lipid intake variations on patients with
      peripheral vascular disease.
AB  - The aim of the present study was to evaluate the effects of diets enriched in
      monounsaturated fatty acids (MUFA) (olive oil) or MUFA plus n-3 polyunsaturated
      fatty acids (PUFA) (olive oil plus fish oil), associated with an intervention
      program that focused on lifestyle habits, physical performance, plasma lipids,
      and lipoprotein composition in patients with peripheral vascular disease (PVD). A
      15-month longitudinal nutritional and lifestyle intervention study was carried
      out with 24 free-living male patients aged 58.0 +/- 2.2 years diagnosed with PVD
      (Fontaine grade II). The patients were clinically evaluated and counseled to
      change their dietary and lifestyle habits for six months, after this period they
      consumed an olive oil-based diet for three months: after a three-month wash-out
      period, their diet was supplemented with a combination of fish oil and olive oil
      for the final three months. Lifestyle interventions resulted in a significant
      decrease in cigarette smoking and an increase in physical activity. Claudicometry
      was lower at the end of the study than at the beginning. Intake of the fish oil
      supplement led to significant changes in lipid lipoprotein composition,
      decreasing low-density lipoprotein (LDL) cholesterol. The lifestyle intervention
      program, together with a high intake of olive plus fish oil, seems to produce
      important beneficial effects in nutritional management, physical performance, and
      clinical parameters of PVD patients.

PMID- 14639805
TI  - [Discovering the authentic Hildegard. Comments on the only in Florance 'Physica'
      handwritten texts].
AB  - The recently discovered ms. of Hildegard's, Physica' (Florence, B. Med.-Laurenz.
      Ashburnh. 1323) contains much more text than the Migne edition, based on Paris,
      BN.lat. 6952, does. Did the Florence ms. add or the Paris ms. omit? A comparison
      of all extant mss. and the edition princeps of 1533 reveals that the corpus of
      items and their order remain essentially the same, whereas the number of recipes
      and applications is in permanent decrease. We also observe an increasing
      reduction of explanatory remarks unique to Hildegard's medical doctrine. The more
      copious text of the Florence ms. must, therefore, be regarded as authentic, and
      it should be made the base of a future edition of the 'Physica'.

PMID- 14639806
TI  - [The autograph letter of K. G. Kuhn about the edition of the Medicorum Graecorum
      opera quae exstand series].
AB  - In this article, an autograph letter by K. G. Kuhn (1754-1840) is being published
      and annotated. It was found glued on the interior surface of the back cover of No
      25 manuscript kept at the University of Thessaloniki (Library of Department of
      Classics). With this letter Kuhn announced the publication of the series
      Medicorum Graecorum opera quae existant to F. H. G. Donkermann ("Privatlehrer in
      Leiden") asking for his assistance to trace a Galenic manuscript at the Library
      of Leiden (most probably the pseudo-galenic treatise [symbol: see text].
      Furthermore, in the same letter Kuhn mentioned the publication of the Galenic
      treatise [symbol: see text], as an example (specimen) of the series that was
      going to follow.

PMID- 14639807
TI  - [Persons, networks and institutions: on the founding of the German Society of
      History of Medicine and Natural Sciences].
AB  - In what way did the process of founding the "Deutsche Gesellschaft fur Geschichte
      der Medizin und Naturwissenschaften" (1901), the world's oldest society for the
      history of science develop? This article combines approaches of the
      historiography of institutions with concepts focusing on individual persons.
      During the early period of the process August Hirsch and Theodor Puschmann were
      the most relevant scientists. The history of the "Gesellschaft Deutscher
      Naturforscher und Arzte" (GDNA) and their annual meetings mirror the difficult
      connection of medical history and medical geography or tropical medicine. It was
      the special ability of Karl Sudhoff to create networks which led to the
      emancipation and foundation of the DGGMN; nevertheless, the preliminary work of
      scientists like Hendrik Peypers, Felix von Oefele, Georg Kahlbaum, Julius Pagel
      or Max Neuburger and others must not be forgotten when analysing the crucial
      years around 1900. Sudhoff was the dominant personality then; different
      conceptions of the new discipline in addition to some severe conflicts are
      documented by newly found manuscripts and correspondences.

PMID- 14639809
TI  - [Paolo Zacchia--the spiritual father of forensic medicine].
AB  - Paolo Zacchia (1584-1659) was the personal physician of the popes Innocent X and
      Alexander VII, legal advisor to the Rota Romana and head of the health system in
      the Papal States. His most important work, written in Latin, is entitled
      "Quaestiones Medico-Legales" and was published in 9 volumes between 1621 and
      1651. Even after Zacchia's death comprehensive reprints were published at several
      places up to the late 18th century. Zacchia covered all the medicolegal issues of
      his time including the problem of "malpractice" and medical ethics. He is rightly
      considered an outstanding representative of his profession, whose "Quaestiones
      Medico-Legales" gave legal medicine its name.

PMID- 14639810
TI  - [Dental caries and fillings in wisdom teeth as an aid in forensic dentistry for
      determining chronologic age over 18. Radiologic studies of orthopantomography
      images of children and adolescents].
AB  - Dental findings are an important source of information regarding forensic
      odontologic determinations of identity and a person's age. A main part of
      odontologic findings is the judgement of the dental status, including caries and
      identification of filled teeth. The aim of this study was to answer the question
      whether fillings of wisdom teeth allow individual age estimation, in particular
      the age of 18 years or older. MATERIAL AND METHODS: The orthopantomograms of 1053
      outpatients were evaluated. The patients were aged 14 to 24 years. For each
      wisdom tooth the values "decayed", "filled", "decayed and filled", or "not
      decayed and not filled" were registered. The data were then calculated using
      tools of descriptive and inferential statistics in order to provide predictive
      values for the age to be above or below 18 years. RESULTS: The majority of wisdom
      teeth in this study group showed neither caries nor fillings. However, the
      correlation between filled wisdom teeth and an age over 18 years was very high,
      up to 100%. DISCUSSION: This study provides for the first time predictive values
      for the estimation whether a person is 18 years of age depending on the presence
      of filled wisdom teeth. This finding is a useful tool for determining the age
      limit of 18 years. The sanitary condition of teeth is dependent from both social
      and individual circumstances. Therefore, the calculated values also reflect the
      culture of the population under study. Further, they are time-dependent and have
      to be compared to data from other populations.

PMID- 14639811
TI  - [Serum cannabinoid levels 24 to 48 hours after cannabis smoking].
AB  - Low concentrations of THC and 11-hydroxy-THC in serum samples are often claimed
      not to result from recent cannabis use. Prediction of time of exposure is
      difficult, especially if distinctive features of drug use could not be observed.
      Therefore, the aim of the study was to investigate the presence of THC and 11
      hydroxy-THC in serum samples as well as to obtain preliminary data on the analyte
      profile for a time window of 24-48 hours after discontinuation of cannabis
      smoking. Serum samples from heavy (n = 12, > 1 joint/day), moderate (n = 11, < or
      = 1 joint/day) and light (n = 6, < 1 joint/week) smokers of cannabis were
      analyzed for THC, 11-hydroxy-THC and free THC-COOH by GC/MS as well as for
      glucuronidated THC-COOH by LC/MS-MS. The blood samples were collected 24-48 hours
      after abstaining from cannabis use. Additionally, 8 specimens were obtained from
      persons after discontinuation of the drug for more than 48 hours. During
      collection of the blood samples, distinctive effects due to drug use could not be
      observed. For heavy users of cannabis, THC was detectable in 8 samples, and in 5
      cases both biologically active compounds, THC and 11-hydroxy-THC, were present
      (1.3-6.4 ng THC/mL serum, 0.5-2.4 ng 11-hydroxy-THC/mL serum). Among moderate
      users, in 1 sample 1.8 ng THC/mL serum and 1.3 ng 11-hydroxy-THC/mL serum were
      determined, and another sample was tested positive with low concentrations close
      to the limit of detection. In serum samples of light users both analytes could
      not be detected, indicating that in those persons a positive finding of THC and
      11-hydroxy-THC may rather result from recent consumption than from cannabis use 1
      or 2 days prior to blood sampling. The concentrations of THC-COOH and its
      glucuronide covered a wide range in all groups of cannabis users. However, there
      was a trend to higher concentrations in heavy users compared to moderate users,
      and the mean concentration was smaller in light smokers than in moderate smokers.
      Overall, the findings indicated that data from pharmacokinetic studies should be
      supplemented by data obtained from "real-life" samples.

PMID- 14639812
TI  - [Fatalities after injuries by wild animals].
AB  - The article summarises three fatalities after attacks by wild animals. The first
      case describes a 90-year-old woman who died as a result of pneumonia after a bear
      fell on her and caused multiple chest fractures. The second case deals with a 76
      year-old woman who was hit in the middle face by the hoof of a camel and,
      thereafter, died of myocardial infarction. The third case describes a 27-year-old
      biologist who died from severe blunt trauma after an attack of a wild living
      elephant. The article gives a summary of typical injury patterns of selected wild
      animals and outlines potential reasons of death as a result of the injuries.

PMID- 14639813
TI  - [Deep incisional neck injuries caused by an electric knife].
AB  - Electric knives, due to the double blades swinging in opposite directions, have a
      high injury potential. Tissues such as skin can be cut smoothly without cutting
      motion and with only little pressure. Authors report on the case of a woman of 47
      years who cut herself deeply on both sides of her neck with an electric knife,
      slightly carving a notch into the larynx and a cervical vertebra and opening
      large blood vessels. With respect to the extent of injuries the capacity to act
      had to be questioned. However, considering the absence of venous air embolism and
      the peculiarity of the tool it had to be assumed that the capacity to act lasted
      for a short time.

PMID- 14639814
TI  - [Capacity for physical action in traumatically-induced epidural hemorrhage].
AB  - Authors report the case of a 55-year-old man with a nearly normal capacity to act
      for appr. 48 hours following epidural hematoma due to a blunt trauma of the head
      with skull fracture. The man was amnestic for the period of time since the
      trauma. According to the computertomographic findings, the cause for the mild
      clinical symptoms was a pre-existent atrophy of the brain.

PMID- 14639815
TI  - [What are your findings and what is your differential diagnosis? Metastasizing
      prostatic carcinoma with histologically documented bronchial metastasis].

PMID- 14639816
TI  - [Spinal tumors: clinical aspects, classification and surgical treatment].
AB  - Spinal tumors are classified in intradural and extradural tumors. Most extradural
      spinal tumors are metastasis. The other spinal tumors are rare and mostly benign.
      Only about 5% of tumors of the nervous system are spinal tumors. Their
      symptomatology is often insidious and the diagnosis can be difficult. Magnetic
      resonance imaging has revolutionized their diagnosis. The lesions within the
      spinal cord can now be directly visualized. The treatment of these tumors mostly
      require surgery. It has been proven that surgical results are better if these
      tumors are operated as soon as neurological symptoms have appeared. In our series
      of 39 operated intradural tumors we noted a functional improvement in 46.5% of
      the cases, a stabilisation in 43.5% and a deterioration in 10%.

PMID- 14639817
TI  - [Do automated hematology counters replace the manual differential count?].

PMID- 14639818
TI  - ["Gout tophi" and heart disease in the family].
AB  - A 35-year old man immigrated from Indonesia presented with "gout tophi" at his
      hands and lower extremities. Mother, aunt and uncle of this patient also suffered
      from "gout tophi" as well as a heart disease not exactly known to the patient.
      Clinical investigation was suspicious for tendon xanthomas and revealed arcus
      lipoides corneae of both eyes. Total cholesterol was 10.5 mmol/l and HDL
      cholesterol was 0.8 mmol/l. Genetic investigation showed heterozygous familial
      hypercholesterolemia, i.e., heterozygous mutation of the gene encoding the LDL
      receptor protein. The patient was treated with atorvastatin 20 mg daily and a low
      cholesterol diet. Total cholesterol decreased to 6.5 mmol/l and HDL cholesterol
      increased to 1.5 mmol/l within 2-month treatment. We recommended the
      determination of serum lipids in further members of this family and genetic
      evaluation of the patient's children with regard to the mutation identified.

PMID- 14639819
TI  - [An 85-year-old patient with recurrent episodes of confusion and absences].

PMID- 14639820
TI  - [Dear colleagues].

PMID- 14639821
TI  - [Probiotics in veterinary medicine: a review].
AB  - The mammalian gastrointestinal tract is a complex consisting of the intestinal
      epithelial cells, the mucosal immune cells and the endogenous microflora. Since a
      couple of years, probiotics are used in animal production to improve performance.
      But there are only few results available on the immune modulating effects of pro-
      and prebiotics in human and veterinary medicine. Recent studies are promising
      that pro- and prebiotics can be used as an alternative to conventional therapy
      with immune suppressive drugs in patients with inflammatory bowel disease or
      dietary hypersensitivity. Yet further randomized and placebo-controlled studies
      are needed to clarify these mechanisms in vivo.

PMID- 14639822
TI  - [Animal health in organic agriculture: new guidelines and perspectives for food
      animal practitioners].
AB  - In the last decade, the organic agriculture in Switzerland has been substantially
      increased due to the interest of consumer and financial incentives of the
      federation. Ruminants take directly or indirectly the largest part from grassland
      used within the organic managed surfaces. As the contacts between veterinary
      practice and organic agriculture has increased, the potential for veterinary
      activity in this area has developed considerably. The organic agriculture
      guidelines stipulate that all the preventive measures should be taken in feeding,
      keeping and breeding to insure animal health safety. This requires veterinary
      services for herd management. The organic status of a farm affects veterinary
      practice also in the form of alternative therapy/drugs administration and
      measures like dehorning and tail-docking. An important point in organic managed
      herds requests that treatment of animals should depend on alternative medical
      preparations or procedures based on veterinarian's experience and also on the
      therapeutic effect on the animal species concerned as well as on the disease.
      However, there are no restrictions on the veterinarian to use registered drugs as
      long as no alternative therapy, according to experience and possible success, is
      available to treat the animals. The prophylactic administration of allopathic
      veterinary drugs is not permissible. Further features in organic farms regarding
      the use of drugs are the keeping of withholding/withdrawal time, the
      documentation and the treatment frequency tolerated by organic marketing. Despite
      the above measures, the animal health has a priority regardless of its organic
      status. Although management of organic farms represent a unique responsibility,
      there are still obvious deficits in the education of veterinary practitioners for
      this new situation. However, in the future the extension of veterinary activity
      to include the alternative medical therapy should be regarded for the
      practitioner as a challenge and an opportunity at the same time.

PMID- 14639823
TI  - [Congenital cardiac diseases in dogs: a retrospective analysis].
AB  - In a time period of 6 years, 158 congenital cardiac defects were diagnosed in 146
      dogs at the Clinic for Small Animal Medicine University of Zurich. In respect to
      all dogs with cardiac disease, these were 23.5% of the cases. Most common defects
      were subaortic stenosis (SAS, 31.5%), pulmonic stenosis (PS, 23.3%), ventricular
      septal defect (VSD, 14.4%), patent ductus arteriosus (PDA, 13.7%) and tricuspid
      dysplasia (TD, 7.5%). Complex defects were found in 8.2% of the dogs. Although
      single dogs per breed were affected by various defects, some breed-related
      tendencies could be observed. We found PS more numerously in boxers and Jack
      Russell Terriers whereas SAS, VSD and TD were also found in breeds reported to be
      predisposed. Congenital cardiac defects are an important clinical entity, and
      knowledge of prevalence is helpful when considering the differential diagnosis
      and for making a tentative diagnosis in an individual case.

PMID- 14639824
TI  - [Home monitoring of blood glucose concentrations by owners of diabetic dogs and
      cats].
AB  - Generation of blood glucose curves is essential to monitor glycemic control in
      dogs and cats with diabetes mellitus. Up till now blood collection and blood
      glucose measurements could only be performed in a hospital. However, glucose
      concentrations measured in a hospital environment can markedly differ from
      concentrations measured at home, due to reduced appetite, different activity
      level and stressful handling. At the Clinic of Small Animal Internal Medicine,
      University of Zurich, a new method to collect capillary blood from the ear and to
      measure blood glucose by means of a portable glucose meter has been developed.
      This method enables owners of diabetic dogs or cats to determine blood glucose
      concentrations and generate blood glucose curves at home. Three cases
      demonstrate, how much blood glucose concentrations at home may differ from those
      in the hospital and how home monitoring can help to establish diabetic control in
      dogs and cats.

PMID- 14639825
TI  - [Lipid reduction without medication. What effect does diet have on lipids?].

PMID- 14639826
TI  - [Causes of vascular injury. Endothelial function, morphology and biochemistry of
      atherosclerosis].

PMID- 14639827
TI  - [Mechanism of action of HMG-CoA reductase inhibitors. Medical-chemical aspects of
      statins].

PMID- 14639828
TI  - [Is LDL reduction the only effect of statins? Pleiotropic effects of statins].

PMID- 14639829
TI  - [Prevention and treatment of coronary heart disease. The importance of
      cholesterol synthesis enzyme inhibition].

PMID- 14639830
TI  - [What should be considered in the administration of cholesterol synthesis enzyme
      inhibitors? Interaction and adverse effect potentials of statins].

PMID- 14639831
TI  - [Cardiovascular risk factor reduction. Cholesterol absorption inhibitors: a new
      action principle].

PMID- 14639834
TI  - [The rights of the embryo].

PMID- 14639833
TI  - [High therapeutic effect and safety of fluvastatin].

PMID- 14639835
TI  - [Life, a damage that may be compensated?].

PMID- 14639836
TI  - [Presence of the mother during wound dressing in the burned child].

PMID- 14639837
TI  - [How far should the level of LDL cholesterol be decreased?].

PMID- 14639838
TI  - [Is there time also for caring?].

PMID- 14639839
TI  - [What patients said about quality].

PMID- 14639840
TI  - [Disease resulting from immobility, prevention of complications].

PMID- 14639841
TI  - Pain management in adult dental patients: the art and science of successful
      regimens.
AB  - Pain is a protective mechanism for the body; it occurs whenever any tissues are
      being damaged, and it causes the individual to react to remove the pain stimulus.
      Most ailments of the body cause pain, and the ability to diagnose different
      diseases depends to a considerable extent on the physician's knowledge of the
      various qualities of pain. In dentistry, pain may be expected, i.e., caused by
      dental procedures, and its management should commence preoperatively. This
      article is a review of pharmacologic pain management in adult dental patients. It
      discusses the pharmacology and therapeutic utilization of opioid and nonopioid
      analgesics and the selection of single and combined analgesic regimens.

PMID- 14639842
TI  - [Warm ischemia in renal surgery, finally accepted].

PMID- 14639843
TI  - [Adrenal surgical pathology. Report of our cases and bibliographic review].
AB  - OBJECTIVES: Adrenal masses have different presentations, from an incidentally
      diagnosed mass to a blooming Cushing's syndrome, this stimulated our interest to
      evaluate and describe our case series over the last 10 years, besides to perform
      a bibliographic update. METHODS: Retrospective and descriptive study of 22
      patients suffering from adrenal masses, evaluating their clinical and
      radiological characteristics, functional disturbances, and histological
      diagnosis, emphasizing the first suspicion or finding suggesting adrenal disease.
      RESULTS: Men were more often affected than women in this series, 12 men vs. 10
      women. Mean age was 51.2 years (33-71). Regarding side, 10 cases were right, 8
      left and 2 presented bilateral disease, one of them bilateral adenoma and the
      other asynchronous renal carcinoma metastasis. The inverted "Y" morphology
      usually observed on CT scan was lost in 14 patients. Size varied between the
      following ranges: 2-4 cm--9 cases, 4-6 cm--12 cases, and one case of a gigantic
      cyst within the left hemi-abdomen. CONCLUSIONS: Results in our series are similar
      to those in the literature, adrenal masses are uncommon and despite their low
      incidence they have different clinical and a histological forms of presentation.
      27% of them were incidental, which represents a significant percentage in
      comparison with other series. Adequate clinical and functional studies as well as
      their radiological characteristics will set the indication for adrenalectomy or
      follow-up. Most cases < 4 cm (7/9) were renal carcinoma metastasis or
      pheochromocytoma. Incidentally diagnosed cases have increased with the
      development of new imaging technologies as well as with more frequent use of
      them. The functional study of adrenal masses has suffered little change. Surgical
      treatment of these pathologies is suffering important changes with the advent of
      laparoscopic urologic surgery.

PMID- 14639844
TI  - [Treatment of urinary stress incontinence using suburethral implantation of
      tension-free vaginal tape (TVT). 4 years' experience].
AB  - OBJECTIVES: To analyze our results in terms of continence and complications of
      treatment of urinary incontinence with TVT during the 4 first years. METHODS: 72
      patients underwent surgery for urinary incontinence between 1999 and 2002. Chart
      review was performed for medical history, physical examination, urodynamic tests,
      surgical procedure, intraoperative and postoperative complications, objective and
      subjective results. RESULTS: 62 patients were diagnosed of genuine stress urinary
      incontinence and 10 patients of mixed urinary incontinence. 14 patients had grade
      3 cystocele, 12 of them underwent associated colporrhaphy. Operations were
      performed under local anaesthesia in 1 patient, spinal anaesthesia in 41 and
      general anaesthesia in 30. Mean operation time was 32 minutes, 66 minutes when
      colporrhaphy was associated, and previous surgery did not increase the surgical
      difficulty. 6 patients (8.3%) suffered bladder perforation which was identified
      during cystoscopy, but only required reposition of the tape without affecting
      patients' outcomes; 1 patient had a pelvic hematoma that evolved without sequel;
      16 patients (22.22%) had urinary retention which spontaneously resolved between 2
      and 60 days, except one case that required section of the mesh. 8 patients
      (11.11%) developed de novo bladder instability; there were 2 cases of late mesh
      perforation into urethra or bladder, which were solved by endoscopic mesh
      section; 3 patients had voiding discomfort and 1 chronic perineum pain. 70
      patients (97.3%) achieved continence under stress; nevertheless only 57 patients
      (79.17%) were satisfied with their outcomes. Main causes for dissatisfaction were
      failure, de novo instability, persistence of urgency in cases of mixed
      incontinence, and voiding discomfort. Previous surgery and performance of
      associated procedures did not influence outcomes, although they were associated
      with longer operation times and higher incidence of urinary retention. Patients
      with Valsalva's leak point pressure < 60 H2O cm had slightly worse outcomes
      (63.5% satisfaction). CONCLUSIONS: TVT is an easy to learn and easy to perform
      technique, with few complications and good results.

PMID- 14639845
TI  - [Diverticula of the female urethra. Our experience].
AB  - OBJECTIVES: To review the pathology of female urethra diverticulum and our own
      experience. METHODS: We review 10 cases of female urethral diverticula studied in
      or Department of Urology. Medical history, symptoms, location, number, size,
      associated lesions, and treatment performed were reviewed. RESULTS: The
      performance of vaginal palpation, voiding cystourethrogram, intravenous
      urography, and transvaginal ultrasound are useful for the diagnosis. The surgical
      technique performed has been transvaginal, with and good results in a 80% (8/10)
      of the cases. CONCLUSIONS: It is a pathology that should be taken into
      consideration in front of recurrent urinary tract infections and relapsing
      irritative lower urinary tract symptoms. Treatment requires surgery, being the
      transvaginal approach the one that gives the best results.

PMID- 14639846
TI  - [Diagnostic utility of cuff flowmetry in lower urinary tract obstruction in men].
AB  - OBJECTIVES:  PRIMARY OBJECTIVE: to investigate the usefulness of cuff flowmetry
      for the diagnosis of lower urinary tract obstruction in males. SECONDARY
      OBJECTIVES: 1) To investigate the relationship between isovolumetric pressure
      (Piso) and bladder contractility. 2) To investigate the relationship between the
      type of flow curves obtained by this method and the type of lower urinary tract
      obstruction, and previous history of prostate surgery. METHODS: We perform a
      cohort study in a series of 93 consecutive males (mean age 54.1 yr.) referred
      with functional lower urinary tract symptoms. They were interviewed about history
      of prostatic surgery, and they underwent isovolumetric pressure measurements
      (Piso), and corresponding flow (Qiso) by means of cuff flowmetry. From these
      parameters we calculated the Riso parameter, defined as Piso/(Qiso)2. A
      conventional pressure/flow study was performed afterwards, with computer
      calculation of urethral resistance parameters--footpoint and PURR curvature--,
      and the bladder contractility parameter Wmax. RESULTS: The diagnostic efficiency
      curve for the Riso parameter showed that the ideal cutpoint corresponded to a
      value of 1.29 cm H2O/(ml/sec)2. For this value the sensitivity for the diagnosis
      of lower urinary tract obstruction was lower than 78% and specificity was 73%. We
      elaborated a nomogram for the relationship between Piso and Qiso using a logistic
      regression model. This nomogram was divided in three areas (obstructive,
      equivocal, and not obstructive). If patients within the equivocal area (9.7% of
      the sample) were excluded, then the nomogram had a sensitivity of 84% and a
      specificity of 73% for the diagnosis of obstruction. We observed a significant
      association between flow curves with an absent initial peak morphology and
      obstruction of the constrictive type. No relationship was demonstrated between
      history of prostate surgery and type of curve. CONCLUSIONS: Cuff flowmetry has an
      acceptable sensitivity and specificity for the diagnosis of lower urinary tract
      obstruction. However, our study did not demonstrate its usefulness for the
      determination of the detrusor contractile capacity. Piso and Qiso parameters
      would be urethral resistance parameters.

PMID- 14639847
TI  - [Clinico-urodynamic correlation in the hereditary ataxias].
AB  - OBJECTIVES: To evaluate lower urinary tract functional symptoms in a series of
      patients with ataxia and to determine by urodynamic studies the kind of bladder
      urethra neurological dysfunction in each case. We posed the question if the
      clinical picture could be enough to establish the diagnosis and therapeutic
      management of these patients with hereditary ataxia, or on the contrary it would
      be necessary to perform urodynamic studies in all cases. METHODS: Due to the low
      incidence of hereditary ataxias and patients' mobility it was necessary to
      recruit patients from various hospitals. The urodynamic study protocol employed
      in this study included 1) Evaluation of urinary symptoms; 2) Neurological
      physical examination; 3) Flowmetry with post void residual; 4) Cystomanometry;
      and 5) Perineal electromyography. We analyzed the relationship between urinary
      symptoms and urodynamic diagnosis, considering variables such as age, gender,
      type of ataxia, and time of evolution of the disease. RESULTS: The series
      includes 34 patients with ataxia and urinary symptoms, 14 cases of Friedreich's
      ataxia (FA) (41.2%) and other 20 cases of other various forms of ataxia we name
      non-Friedreich's (NF) (58.8%). Mean age was 37.2 years in FA and 50 years in NF
      (p < 0.05). Mean time of disease evolution was 20.5 yr. for FA, and 14.9 yr. for
      NF ataxia (p < 0.1). A mixed urinary syndrome was predominant in 53% of the
      patients, and 41.1% presented pure irritative symptoms in relation to voiding
      urgency (85.2%). The most frequent urodynamic diagnosis was detrusor
      hyperreflexia (61.7%) (37.5% with dyssynergia), followed by areflexia (or
      hyporeflexia) (23.5%), and normal studies (14.7%). Detrusor hyperreflexia
      presented with irritative urinary symptoms in 85.7% of the patients, and
      areflexia or hyporeflexia presented with obstructive symptoms in 75% of the
      cases. CONCLUSION: Although there is a good clinical-urodynamic correlation in
      cases of ataxia, we consider it is necessary to perform a complete urodynamic
      study in males with hereditary ataxia in order to rule out bladder outlet
      obstruction due to BPH. On the other hand, due to the fact that progression of
      the lesions can modify the clinical picture of the patient (including urinary
      tract symptoms), we consider essential to re-evaluate ataxic patients
      periodically to adapt their treatment to the urodynamic diagnosis.

PMID- 14639848
TI  - [Treatment of childhood lithiasis using extracorporeal shock wave lithotripsy].
AB  - OBJECTIVES: We evaluated the efficiency of extracorporeal shock wave lithotripsy
      (ESWL) in the treatment of pediatric urolithiasis, analyzing results and
      complications in our series. METHODS/RESULTS: 20 patients (16 males and 4
      females) with ages from 2 to 17 years were evaluated. Twelve patients presented
      left side lithiasis (60%). The size of the stone was measured in cm2 areas. 6
      cases (30%) presented with lower calyx stones and 5 cases (25.9%) with stones in
      the pelvic ureter. 2 patients required JJ catheter insertion. Mean number of
      shock waves per session was 2,650 (range: 1,000-3,800). The Dornier Lithotripter
      S and Dornier MFL-5000 lithotripsy machines were used in the range of 10-120 Kv
      and 14-23 Kv respectively. Follow-up evaluation was performed at one week and
      three months from treatment, including abdomen x-ray to obtain fragmentation and
      elimination percentages. In our series total fragmentation was achieved in 100%
      of the cases, without any patient with partial fragmentation (fragments > 5 mm).
      Elimination percentages were satisfactory, with a 65% total elimination and 30%
      partial elimination (residual fragments < 5 mm) within one week. One patient had
      no elimination at all. CONCLUSIONS: After the results obtained in our series, we
      consider external shock wave lithotripsy the first treatment option in cases of
      pediatric urolithiasis.

PMID- 14639849
TI  - [Treatment of reno-ureteral lithiasis with ESWL in obese patients. Apropos of 150
      patients].
AB  - OBJECTIVES: Obesity is considered a significant risk factor for diseases such as
      hypertension, diabetes, coronary artery disease, and metabolic diseases,
      increasing considerably the risk for surgery. We have treated with ESWL a
      significant number of patients with the aim of avoiding operations which could be
      long and have associated complications due to the patient's condition. METHODS:
      From April 2000 to May 2002 we treated 150 obese patients with kidney and/or
      ureteral stones using a Nova Ultima lithotripter. 94% of the patients were
      treated with a neuroleptoanalgesic drug, and 6% of the cases required narcotic
      neuroleptoanalgesia. 85% of the cases were admitted for 24 hours, and 15% were
      outpatient. 94 males and 56 females who weighted more than 90 kg (91-141 kg) and
      more than 80 kg (80-127 kg) respectively were treated. Mean age was 41 years
      (range 20-72). 134 stones were located in the kidney, 27 in the pelvis and 16 in
      the ureter (25 patients presented bilateral lithiasis and 2 one ureteral stone
      and one homolateral kidney stone). Mean stone size was 12 mm. Stone track down
      was easy in 64% of the cases and difficult in 36%, mainly ureteral and pelvic
      stones. All patients received 3,000 shock waves at 21-22 KV and high energy with
      an average time per session of 35 minutes. Ultrasound tracking was preferred in
      80% of the patients. RESULTS: Results at three months were: 72% stone-free, 9% <
      4 mm, 14% > = 4 mm, and 5% failures. Best results were obtained in pelvic and
      lumbar ureter stones (88%). Mean retreatment was 1.6, with one additional session
      in 34 patients, two sessions in 8, and three sessions in 5. CONCLUSIONS: In the
      treatment of urolithiasis in obese patients, lithotriptor machine characteristics
      and operator experience are very important. The knowledge and the application of
      stone tracking systems allow the urologist to obtain a higher percentage of stone
      free patients. These techniques are important in these patients because
      positioning is key to obtain a good result. The indication of ESWL in obese
      patients is a good choice but selection criteria should be respected. The
      percentage of stone free patients at three months has been satisfactory and
      complications are similar to those published by other authors.

PMID- 14639850
TI  - [Prostatic epidermoid carcinoma: report of a new case an review of the
      literature].
AB  - OBJECTIVES: To study and to review the squamous cell carcinoma of the prostate
      (SCCP). METHODS: We report one case of squamous cell carcinoma of the prostate.
      RESULTS: A 78-year-old patient was diagnosed of having a squamous cell carcinoma
      of the prostate. Clinically, the patient presented with severe irritative lower
      urinary tract symptoms. Treatment was performed by local radiotherapy and
      response was poor, as it usually happens in this type of tumors. Patient survived
      seven months after diagnosis. We present the clinical case and a bibliographic
      review. CONCLUSIONS: SCCP is a rare, difficult to diagnose and poor in prognosis
      tumor with very few therapeutic options.

PMID- 14639851
TI  - [Encrusted pyelitis in a transplanted kidney].
AB  - OBJECTIVES: To emphasize the importance of early diagnosis of encrusted pyelitis
      in kidney transplant patients. METHODS: We report one case of encrusted pyelitis
      in a 10-year-old girl with a kidney graft who was treated by means of nephrostomy
      tube irrigation with an acidifier liquid substance. RESULTS: After 16 days of
      treatment there was a significant decrease of the size of the calcified pyelic
      plaque, keeping a good renal function afterwards. CONCLUSIONS: This disease
      should be thought of in every case of kidney transplant patient with negative
      urine cultures and alkaline pH, and the microbiologist should be alerted of the
      possibility of urinary tract infection by Corynebacterium.

PMID- 14639852
TI  - [Cystic renal papillary carcinoma. Apropos of a case].
AB  - OBJECTIVES: Papillary renal cell carcinoma is a malignant neoplasia which
      represents 5-10% of all renal cell carcinomas. We perform a bibliographic review,
      and detail the clinical, diagnostic and therapeutic aspects of the case, as well
      as its postoperative outcome. METHODS: 55-year-old patient who was admitted in
      the urology department from the emergency room. On physical examination we
      detected a mass in the left flank and left upper abdominal quadrant, painful on
      flank percussion, and gross hematuria also. It was a patient who debuted with
      left lumbar-abdominal pain and hematuria with clots after a physical effort.
      Blood tests, ultrasound, x-rays and surgical treatment were performed. RESULTS
      AND CONCLUSIONS: On evaluation of the ultrasound and x-ray films it was concluded
      that it was a significant renal tumor. Left radical nephrectomy was performed and
      pathology reported papillary renal cell carcinoma. Postoperative outcome was
      satisfactory after three months.

PMID- 14639853
TI  - [Giant scrotal lymphedema caused by Milroy's disease].
AB  - OBJECTIVES: To report a new case of giant scrotal lymphedema due to Milroy's
      disease, its treatment and outcome. METHODS: A 27-year-old man with generalized
      congenital lymphedema presented with a giant scrotal mass which interfered with
      his daily activities and physiological necessities. Physical examination showed a
      scrotal mass 40 x 40 cm in size and a normal penis. CT scan showed a homogeneous
      mass, thickened vaginal tunica, and bilateral hydrocele. RESULTS: A surgical
      procedure was performed including mass resection (5.6 kg), and bilateral
      hydrocelectomy. Skin defect was covered with skin grafts. CONCLUSIONS: Several
      therapeutic alternatives have been suggested for Milroy's disease with genital
      involvement. Nevertheless, when complications are as severe as in the present
      case, the only valid therapy is surgery.

PMID- 14639854
TI  - [A new case of bladder endometriosis in a patient with a history of Cesarean
      section].
AB  - OBJECTIVES: To report one new case of endometriosis in a patient with history of
      caesarean section. METHODS: It is the case of a female patient presenting with
      voiding symptoms and hematuria, with a bladder tumor on ultrasound. RESULTS:
      After TUR of a retro trigonal tumor pathology report showed bladder
      endometriosis. Treatment was completed with hormone therapy, being the patient
      relapse free at one year follow-up. CONCLUSIONS: History of caesarean section is
      one of the possible etiologies of bladder endometriosis.

PMID- 14639855
TI  - [Testicular leukemic infiltration].
AB  - OBJECTIVES: To remind that despite its low incidence, leukemic relapse in the
      testicles worsens the prognosis of this haematopoietic neoplasia.
      METHODS/RESULTS: We report the case of a 20-year-old male suffering from acute
      lymphoblastic leukemia in complete remission after induction and maintenance
      treatment, who suffered a leukemic relapse in both testicles. Diagnosis was made
      by ultrasound and confirmed after bilateral testicular biopsies. The patient died
      due to fungal infection after new treatment with systemic chemotherapy and bone
      marrow transplantation. CONCLUSIONS: It is necessary to suspect the existence of
      leukemic cells within the testicles in patients with this disease, mainly acute
      lymphoblastic leukemia, who present with acute testicular symptoms. Testicular
      biopsy confirms the diagnosis. Treatment is systemic, with testicular radiation
      to eradicate the leukemic reservoir. Despite the achievement of local disease
      control, this situation worsens the prognosis.

PMID- 14639856
TI  - [Mesonephroid adenocarcinoma. Apropos of a new case and review of the
      literature].
AB  - OBJECTIVES: Mesonephric adenocarcinoma is a rare clinical entity, predominantly
      appearing in women, involved in great controversy about its histogenesis.
      Reported cases to date were not diagnosed in their initial stages and they were
      treated by radical surgery with poor results. METHODS: We report the case of a 71
      year-old male with previous diagnosis of nephrogenic adenoma two years before.
      RESULTS: After the diagnosis of mesonephric adenocarcinoma was established,
      patient underwent radical surgery despite its poor prognosis. CONCLUSIONS:
      Differential diagnosis between these tumors should be made with primary or
      metastatic adenocarcinoma and nephrogenic adenoma. We highlight the ongoing
      controversy in the literature in relation to malignant evolution of the
      nephrogenic adenoma as etiology of the rare mesonephric adenocarcinoma. In this
      case, previous finding of a nephrogenic adenoma would support that theory.

PMID- 14639857
TI  - Small renal mass: report of one case and bibliographic review.
AB  - OBJECTIVES: We present a new case of small renal mass in which monitoring was
      chosen, no surgical intervention, and review of literature about this. METHODS
      AND RESULTS: We present a case of a female, 80 years of age, who was diagnosed of
      small renal mass (2 cms). We monitored the patient every 6 months through C.T.
      After more two years the renal mass is the same. CONCLUSIONS: In case of renal
      mass lower than 4 cm without local invasion we can choose the option of
      periodical monitoring with C.T. (6 monthly). It is important that the patient is
      assymptomatic. So therefore given the age (80 years), size of the tumor, and
      absence of symptoms, we can do monitoring without surgery.

PMID- 14639858
TI  - [MHC tetramers: tracking specific immunity].
AB  - In an adaptive immune response, antigen is recognized by two distinct sets of
      highly variable receptor molecules: (1) immunoglobulins, that serve as antigen
      receptors on B cells and (2) the antigen-specific receptors on T cells. T cells
      play important role in the control of infection and in the development of
      protective immunity. These cells can also mediate anti-tumor effects and, in case
      of autoimmune syndromes, contribute to the development and pathology of disease.
      The specificity of T cells is determined by T cell receptors (TCR). Understanding
      of the success of immune responses requires the direct measurement of antigen
      specific T lymphocytes. Cell with major histocompatibility complex (MHC) class I
      molecules are able to present antigens to antigen-specific CD8+ cytotoxic T
      lymphocytes. MHC class I molecules present small peptides (epitopes) processed
      from intracellular antigens such as viruses and intracellular bacteria. MHC class
      I molecules in humans are designated as human leukocyte antigen (HLA) class I and
      divided into HLA-A, -B and -C. CD8+ T cells recognize MHC class I molecules and
      after activation produce proteins that destroy infected cells. MHC class II
      molecules receive their peptides mainly from extracellular and soluble antigens
      and present them to the CD4+ T helper cells. A recently described technique that
      can be used in flow cytometry enables us to quantify ex vivo antigen-specific T
      cells by binding of soluble tetramer MHC-peptide complexes attached to
      fluorochrome. Quantitative analyses of antigen-specific T cell populations
      provide important information on the natural course of immune responses. The
      interaction of T cell receptors on T lymphocytes with tetrameric MHC-peptide
      complexes mimics the situation on the cell surface, and allows for reliable
      binding. Tetramers consist of four biotinylated HLA-peptide epitope complexes
      bound to streptavidin conjugated with fluorescent dye. Tetramer technology has
      sensitivity of detection as little as 0.02% of total cytotoxic T cell pool or T
      helper cell pool (i.e. approximately 1 in 50.000 lymphocytes). The combination of
      this technology with intracellular cytokine staining methods opens up
      significantly better ways of studying these cells than previously possible,
      allowing immunologists to look at their life cycle (activation and
      proliferation), manner of death (aging and apoptosis) and effector function
      (cytotoxic potential and cytokine production). MHC tetramers class I have yielded
      useful insights into in vivo dynamic and function of antigen-specific CD8+ T
      cells in viral infections, parasitic infections, cancer, autoimmune disease and
      transplantation. This knowledge is of special interest for immunotherapy,
      diagnostic monitoring of T cell mediated immunity, and the development of new
      vaccination strategies. There is some possibility for cell therapy with antigen
      specific CD8+ T cells for various diseases including cancer and viral infections.
      Targeted immunotherapy of selective deletion of auto--or alloreactive T cells
      with MHC tetramers may be important for the treatment of autoimmune disease, or
      to prevent the rejection of transplanted organs. The utility of this technique
      for the immunotherapy in vivo needs to be confirmed and modified in further
      research. Understanding how antigen-specific cells develop and function in
      different circumstances and pathologies will be the key to unravelling the
      secrets of cellular immune system.

PMID- 14639859
TI  - [Non-Hodgkin's lymphoma: clinical symptoms, therapy and prognosis in 37
      patients].
AB  - Clinical characteristics and prognostic factors in 37 patients with the diagnosis
      of non-Hodgkin's lymphoma made during the 1980-1998 period were retrospectively
      analyzed. Median age was 70 years, and 70% of patients were aged > 60. The
      disease was classified according to REAL classification. Twenty-seven (73%)
      patients had B cell lymphoma, and 10 (27%) patients had T cell lymphoma. Indolent
      lymphoma was diagnosed in 14, and aggressive lymphoma in 23 patients. Performance
      status as assessed according to the Eastern Cooperative Oncology Group scale was
      0 or 1 in 73%, and worse in 27% of patients. The presence of B symptoms was
      recorded in 49% of patients. Lymph nodes exceeding 5 cm in size were found in 35%
      of patients. Erythrocyte sedimentation rate > 40 mm/h was recorded in 43%, and
      hemoglobin values < 125 mg/L in 73% of patients. Leukocytes were within the
      normal limits, i.e. below 10 x 10(9)/L, in 81%, whereas lymphocytes were within
      the normal limits in 86% of patients. Thrombocytopenia was recorded in 24%, and
      bone marrow infiltration at the time of diagnosis in 65% of patients. Complete or
      partial response rate was achieved by first-line therapy in 73% of patients,
      whereas 27% of patients failed to respond or their condition worsened. Median of
      the expected survival was 60 months for indolent lymphomas and 29 months for
      aggressive non-Hodgkin's lymphoma. Statistically relevant parameters for complete
      response in univariate analyses are performance status of the patient,
      International Prognostic Index and platelet count. In multivariate analysis, the
      only statistically independent prognostic factor is serum lactate dehydrogenase
      concentration (p = 0.037). The study confirmed the prognostic relevance of the
      parameters of the patient general condition according to the World Health
      Organization scale, International Prognostic Index and platelet count for
      complete response in univariate analyses. The only independent prognostic factor
      for the survival was serum lactate dehydrogenase concentration. The prognostic
      value of the International Prognostic Index was also confirmed.

PMID- 14639860
TI  - [Changes in autonomic control of heart rate after ischemic cerebral stroke].
AB  - BACKGROUND AND PURPOSE: Heart rate variability (HRV) is a physiological
      phenomenon which reflects the influence of the autonomic nervous system on the
      heart work. The research in HRV has not been limited to the domain of basic and
      clinical cardiology, mostly with the aim of stratifying the risks of sudden death
      from malignant arrhythmias among patients with myocardial infarction (MI), but
      over the past few years the research has been done and studies have been
      published also in the area of neurology. Likewise acute MI, acute ischemic stroke
      leads to autonomic dysbalance and lowered HRV. However, literature lacks relevant
      data on autonomic dysbalance after the acute phase of ischemic stroke. The aim of
      this study was to assess the level of autonomic dysbalance in patients after the
      acute phase of ischemic stroke. PATIENTS AND METHODS: This prospective study
      included 86 consecutive patients who had suffered ischemic stroke (59 men and 27
      women, mean age 56 +/- 13 years) and 86 age-matched healthy control subjects (62
      men and 24 women, mean age 53 +/- 9 year). In the acute phase of the disease,
      along with clinically manifest neurologic deficit, there is ischemic hemispheric
      lesion verified by computed tomography (CT) scan. Lesion of the left and right
      cerebral hemisphere was detected in 56% and 44% of patients, respectively. After
      the acute phase of the disease, patients were hospitalized at one of the
      neurologic departments of the Hospital for Medical Rehabilitation in Krapinske
      Toplice, Croatia, where rehabilitation was carried out (mean duration 20 +/- 9
      days) in the 1999-2002 period. Inclusion criteria were: age under 70 years, first
      ischemic stroke verified by CT scan within 2-12 weeks of the acute phase of the
      disease, Barthel index 30-50, and stable sinus rhythm in ECG. Exclusion criteria
      were: a history of previous ischemic stroke, intracerebral hemorrhage, MI,
      percutaneous coronary intervention or surgical revascularization of the
      myocardium, clinical signs of coronary artery disease, acute heart failure,
      diabetes mellitus, chronic atrial fibrillation, sinus node disease, AV block
      grade II or III, and the use of beta adrenergic blockers or antiarrhythmic agents
      class Ic or III in medication. Twenty-four hour Holter ECG was performed 58 +/-
      23 days after the stroke (14 +/- 5 days from the beginning of rehabilitation).
      HRV was analyzed from the Holter ECG data. The values of the HRV parameters in
      stroke patients were compared with those recorded in the control group. Most of
      the variables proposed by the Task Force on HRV were analyzed. Time domain
      analysis included: mean RR, mean of R-R intervals for normal beats; SDNN,
      standard deviation of all normal R-R intervals; SDNN-i, mean of 5-minute standard
      deviations of RR intervals; SDANN-I, standard deviation of the 5-minute means of
      R-R intervals; rMSSD, square root of the mean of the squared successive
      differences in R-R intervals; and pNN50, percentage of R-R intervals that are by
      at least 50 ms different from the previous interval. Frequency domain analysis
      included: TP, total power (0.0-0.5 Hz); VLF, very low (0.0033-0.04 Hz); LF, low
      (0.04-0.15 Hz); HF, high (0.15-0.40 Hz) frequency components; and LF/HF, low to
      high frequency ratio. Statistical analysis was performed using the commercial
      software package, Microsoft SPSS for Windows, Version 8.0. RESULTS: Patients who
      had suffered an ischemic stroke had a significantly lower overall HRV and shorter
      mean RR interval than healthy subjects from the control group: SDNN 96 +/- 27 vs.
      136 +/- 31 ms, p < 0.001; TP 1962 +/- 1338 vs. 3968 +/- 2857 ms2, p < 0.001; and
      mean RR 869 +/- 104 vs. 892 +/- 117 ms, p = 0.02. CONCLUSION: As in MI, the
      values of HRV stay significantly lower after the acute phase of the disease in
      patients who have suffered ischemic stroke compared to healthy persons of the
      same age.

PMID- 14639861
TI  - [Cardiovascular neuropathy in pregnant women with type 1 diabetes].
AB  - OBJECTIVE: Autonomic neuropathy has recently been recognized as a potential risk
      factor in pregnancy of type 1 diabetics. The aim of the study was to highlight
      this poorly recognized problem in the obstetric management of diabetic mothers.
      STUDY DESIGN: 94 pregnant type 1 diabetics aged 20-35 with a minimum five--year
      duration of diabetes. A normal population, i.e. 46 age-matched pregnant women
      without diabetes were evaluated, because there are no normal values for this
      population. Cardiovascular tests and structured clinical examination were
      performed on 3 occasions 3 times during pregnancy (once in each trimester).
      Cardiovascular tests were performed using the ProSciCard system. A full test
      battery were performed and six basic tests were evaluated. HbA1c was used to
      assess diabetes control. Diabetic polyneuropathy was clinically assessed by
      Dyck's staging system. RESULTS: The incidence of moderate and severe autonomic
      neuropathy in type-1 diabetic pregnant women was 8.5%. There was no increase in
      the perinatal morbidity and mortality associated with moderate and severe
      autonomic neuropathy. CONCLUSION: The presence of moderate to severe symptomatic
      autonomic neuropathy in patients with type-1 diabetes is not a contraindication
      for pregnancy. If pregnancy is achieved, the patients should be monitored for the
      occurrence of pernicious vomiting.

PMID- 14639862
TI  - [Prevalence of symptoms of asthma, allergic rhinitis, conjunctivitis and atopic
      eczema: ISAAC (International Study of Asthma and Allergies in Childhood) in a
      population of schoolchildren in Zagreb].
AB  - OBJECTIVE: Numerous studies of the population prevalence of asthma, allergic
      rhinitis, and atopic eczema revealed some international differences. However, the
      International Study of Asthma and Allergies in Childhood (ISAAC) was the first
      one using a standardized methodology to evaluate the prevalence of these
      diseases, and to make comparisons within and between countries. The results
      showed marked variations in 12-month prevalence of asthma, allergic
      rhinoconjunctivitis, and atopic eczema symptoms with 20-fold (range 1.6-36.8%),
      30-fold (range 1.4-39.7%), and 60-fold (range 0.3-20.5%) differences between the
      centres with the highest and the lowest prevalence, respectively. AIM: Our aim
      was to gain the insight into the prevalence of allergic diseases in Zagreb,
      Croatia by the methods of internationally standardized protocol, proposed by the
      ISAAC Steering Committee. METHODS: Original questionnaires, translated from
      English into Croatian, consisting of questions about the child's demographic
      characteristics, core modules on wheezing, rhinitis and eczema, and supplementary
      modules, were completed by parents of 10-year-old children (4th grade) attending
      18 elementary schools in a city of Zagreb. Total of 1047 questionnaires were
      returned and analysed after the inconsistent responses were eliminated by phone
      calling. DISCUSSION: Phase one of the ISAAC study has shown a wide variation in
      the prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema
      symptoms throughout the world, with differing international patterns for the
      different disorders. Four prevalence ranges have been established for better
      illustration of the geographic distribution of asthma prevalence: (I) < 5%; (II)
      5 to < 10%; (III) 10 to < 20%; (IV) > or = 20%. The highest 12-month prevalences
      of asthma symptoms were found in developed countries (UK, Australia, New Zealand,
      Republic of Ireland, and most centres in North, Central, and South America),
      being in prevalence range IV. The lowest prevalences (range I) were found in
      several Eastern European countries, Indonesia, Greece, China, Taiwan, Uzbekistan,
      India, and Ethiopia. According to the results of our study, a continental part of
      Croatia with a 12-month prevalence of wheezing of 6.02% corresponds to range II.
      Prevalence of asthma symptoms was greater in males, which is consistent with the
      results of the younger age group previously analysed. For allergic
      rhinoconjunctivitis and atopic eczema symptoms grouping of centres with a high
      prevalences into specific regions was less well defined than for asthma. Centres
      with the highest prevalences were scattered across the world. In contrast,
      centres with the lowest prevalences were similar to those for asthma symptoms.
      Our results of the 12-month prevalence of allergic rhinoconjunctivitis (12.13%),
      and atopic eczema (7.83%) symptoms were somewhere between the two extremes. As
      with asthma symptoms, the prevalence of rhinoconjunctivitis symptoms was greater
      in males. Contrary, the difference in prevalence of atopic eczema symptoms
      between the sex groups has not been found. The worldwide variations in prevalence
      of asthma, allergic rhinoconjunctivitis, and atopic eczema symptoms suggest that
      environmental factors may be critical to the development of these disorders in
      childhood. Furthermore, different patterns of geographical distribution of
      particular disorders suggest that major risk factors for them may be different or
      may involve different latency periods and time trends. Therefore, studies that
      include objective clinical assessment are required. CONCLUSION: According to our
      results, Zagreb is a city with relatively low prevalence of allergic diseases
      symptoms. Larger sample size of at least 3000 subjects is required to provide
      sufficient precision for estimates of symptom severity, and to generate adequate
      number of subjects with particular disorders for further analyses. Therefore, we
      recently increased our sample size to more than 3000 subjects, and started ISAAC
      Phase two (clinical examination, measures of bronchial hyperresponsiveness,
      measures of atopy, measures of environmental exposure to aeroallergens, and
      genetic analyses) in Zagreb, Croatia.

PMID- 14639863
TI  - [Diagnosis and therapy of cervical insufficiency].
AB  - Cervical insufficiency is one of the risk factors for late spontaneous
      miscarriage and preterm labor. As cervical insufficiency can reoccur in the every
      subsequent pregnancy, there is a need for precise diagnostic modality and
      therapeutic procedure in order to reduce perinatal mortality and morbidity.
      Traditionally, the diagnosis of cervical insufficiency was made based on the
      patient's history. In this cases the intervention in the form of the cervical
      cerclage, was not found to be useful, i.e. perinatal mortality and morbidity
      remained unchanged. It is a similar situation in cervical insufficiency suspected
      based on hysterosalpingography and clinical examination. Recently, ultrasound, or
      more precisely transvaginal cervical assessment--cervicometry, was introduced in
      order to assess the morphological changes indicative for cervical insufficiency.
      In this literature review, we analyzed ultrasound based markers of cervical
      insufficiency, with their specificity, sensitivity, positive and negative
      predictive value, as well as usefulness of cervical cerclage in such cases.

PMID- 14639864
TI  - [Detection of human papillomaviruses and other agents causing sexually
      transmitted diseases with molecular diagnosis methods].
AB  - Causative agents of sexually transmitted diseases (STD) are different types of
      bacteria, viruses, fungi and protozoa. The last two decades of the twentieth
      century were marked with a sudden rise in the number of cases of STDs. Human
      immunodeficiency virus (HIV), which emerged in the 1980s, is the most prominent
      STD agent because of its fast spread and severity of the disease it causes,
      acquired immunodeficiency syndrome (AIDS). Beside HIV, human papillomaviruses
      (HPVs), herpes simplex viruses (HSVs) and Chlamydia trachomatis are nowadays
      among most health-threatening STD pathogens. In order to stop the spread of
      infection, apart from education about precautions, early detection of the disease
      is essential. Although most STD pathogens can be detected by classical methods of
      cultivation, biochemical and/or serologic methods, molecular diagnosis of
      infectious diseases has largely simplified and accelerated their detection. For
      instance, HPVs that cause benign and malignant tumors of genital skin and mucosa
      cannot be routinely detected on cell culture, whereas serologic analysis is not
      sensitive and informative enough. Moreover, cytologic (Pap smear) and histologic
      analyses can indicate changes associated with HPV infection, but neither of these
      methods can prove the presence of HPV. That is why the molecular methods are
      essential to demonstrate the presence of the infection and, even more important,
      to determine the type of the virus, which is associated either with low-grade or
      high-grade genital lesions. There are numerous methods based on hybridization
      with DNA or RNA probes, some of them are suitable for detecting wide range of
      types and screening of large collection of samples. However, the most sensitive
      and informative methods are based on polymerase chain reaction (PCR), and they
      have the advantage of being able to determine the type of the virus and
      distinguishing between multiple infections. Herein, we present when and why
      molecular analysis is useful and necessary for the detection of STD agents.

PMID- 14639865
TI  - [Surgical treatment of ophthalmologic complications in Behcet's disease].
AB  - Behcet's syndrome is a chronic multisystem disease with recurrent oral and
      genital ulcerations and recurrent, usually bilateral uveitis. A 31-year-old
      female patient with uveitis who underwent vitrectomy is presented.

PMID- 14639866
TI  - [Plunging ranula].
AB  - Saliva extravasation from the sublingual gland causes ductal lesion or
      obstruction and results in the formation of a ranula. It spreads through or
      behind the mylohyoid muscle situated on the neck. Most frequently it is located
      in the submandibular or submental region. The diagnosis of plunging ranula is
      simple if the signs of ranula are present in the intraoral cavity, whereas in
      case of a ranula localized on the neck definite diagnosis is made by histologic
      analysis of the pseudocyst that has been surgically excised in toto. Cases are
      presented of both types of plunging ranula treated by various surgical
      approaches. Plunging ranula in the submental region was treated by transoral
      approach, marsupialization and aspiration of the content, whereas the ranula in
      the submandibular region was treated by exterior cervical approach. In both
      cases, sublingual gland was removed. During the 3.5-year follow-up, neither
      recurrence of the disease in the neck area nor the occurrence of simple ranula in
      the intraoral region was observed.

PMID- 14639867
TI  - [Suppurative coxitis after a viper bite--case report].
AB  - A 46-year-old woman having sustained a rhinoceros viper bite to the left lower
      leg is presented. She was treated at Department of Infectious Diseases, Split
      University Hospital. After 20 days she left the hospital in good condition, with
      a small crust at the bite site. About ten days later suppurative secretion
      developed at the bite site and a few days later she felt pain in her right hip
      and leg, and turned febrile. She was treated at home with antibiotics and
      analgetics for nearly one month. Her condition was worsening, and she was
      referred to Department of Neurosurgery, for suspected lumboischialgia. Then, she
      was transferred to the Department of Orthopedics as suspected septic coxitis,
      where she was operated on. The disease was not recognized on time, appropriate
      treatment was introduced too late, and irreparable consequences developed in the
      right hip. To the best of our knowledge, this is the first reported case of
      coxitis, especially on the contralateral side to the snake bite. Infection from
      the site of snake bite on the left lower leg could have been transferred to the
      right hip exclusively by hematogenous way. Our objective is to warn of this rare
      snake bite complication, and to contribute to better diagnostic and therapeutic
      management in similar situations.

PMID- 14639868
TI  - [Leiomyosarcoma of the breast].
AB  - A 62-year old patient was treated at our hospital for a palpable change in the
      upper part of the left breast. The clinical finding was preoperatively confirmed
      by radiologic, ultrasound and cytology studies, however, the potential biologic
      process (malignant/benign) was not thus verified. Considering undefined
      diagnostic nature of the process, biopsy, pathohistology and immunoanalysis were
      performed to indicate leiomyosarcoma mammae. The incision interspace at certain
      sites was less than two centimeters, indicating radical breast excision in toto
      (ablation with evacuation of the contents of the axilla). At the time of
      scheduled surgery, the patient sustained cardiologic discomfort, so tumorectomy
      was supplemented by locoregional radiotherapy. Leiomyosarcoma of the breast is a
      very rare primary malignant breast tumor, with only 14 cases reported in the
      literature. Considering the rare occurrence of leiomyosarcoma of the breast, in
      radical surgery we used attitudes like in other breast tumors and leiomyosarcoma
      of other localizations.

PMID- 14639869
TI  - [Continuous venovenous hemofiltration as a bridge to heart transplantation in a
      patient with congestive heart failure and acute renal failure].
AB  - Continuous venovenous hemofiltration effectively controls volume overload in
      cases of severe congestive heart failure accompanied by acute renal failure that
      could not be medicamentously controlled. A patient with severe ischemic dilated
      cardiomyopathy who developed acute renal failure while waiting for urgent heart
      transplantation is described. He was treated with CVVH for three days when the
      occasion for heart transplantation appeared. At the time of transplantation
      laboratory markers of renal function were within the normal range with stable
      hemodynamic parameters. After successful transplantation the patient
      spontaneously and completely recovered his renal function.

PMID- 14639870
TI  - [Prevalence of psoriatic arthritis in a population of patients with psoriasis].
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease
      characterized by arthritis associated with psoriasis. AIM OF THE STUDY: The aim
      of the study was to determine the prevalence of psoriatic arthritis in a
      population of patients with psoriasis. According to literature data, its
      prevalence varies between 1% and 7%, or only exceptionally more. PATIENTS:
      Seventy-two adult patients with psoriasis were examined. Patients came from the
      north-west part of Croatia, from different towns with the overall population of
      more than 150,000, thus making a representative epidemiological sample. Some
      patients were treated by a dermatologist, whereas others were admitted to
      rheumatology departments for the problems with locomotor system and were
      diagnosed as psoriatics. All patients were examined, and their data were
      processed. RESULTS: Statistical analysis showed the two sexes to be equally
      involved by psoriasis. In most cases psoriasis preceded arthritis. All arthritis
      patients had their fingernails affected with psoriasis. In the population of
      patients with psoriasis, the prevalence of arthritis was higher in men (60%) than
      in women (40%). Arthritis often occurred (37.5%) in patients with psoriasis
      localized in the inguinal and/or perianal region with toenail involvement, as
      compared to 8.9% of patients with arthritis without concurrent psoriasis
      involvement. CONCLUSION: The prevalence of arthritis in psoriasis patients was
      15.3%.

PMID- 14639871
TI  - [Academic homage to Professor Jean Van Geertruyden].

PMID- 14639872
TI  - [Mysteries of viral latency and reactivation].
AB  - Varicella-zoster virus is a Herpesvirus responsible for three distinct clinical
      features: chicken pox (varicella), shingles (herpes zoster) and post-zosterian
      pain (post-herpetic neuralgia). Neurological features of these diseases such as
      complications of chicken pox, viral latency in sensory ganglia and reactivation
      as shingles with concurrent and possibly subsequent prolonged pain, are the
      sequels of the invasion of the peripheral nervous system during primary
      infection. Prevention is achieved by vaccination with a live attenuated virus
      strain and therapy calls for specific antiviral agents. In many respects, vzv
      behaves differently from close relatives. In particular, viral latency in the
      nervous system is basically different from that of other Herpesviridae. The
      recent discovery of the expression of some viral regulatory proteins during
      latency, although it had always been considered that vzv latency was silent, and
      demonstration that these proteins are immunogenic open new avenues concerning the
      immune control of vzv reactivation.

PMID- 14639873
TI  - [Neurophysiologic mechanisms of face recognition].
AB  - During the last three decades, the mechanisms implicated in face perception and
      recognition, have been investigated with an interdisciplinary approach. On one
      hand, in psychology, models of cognitive architectures have been developed in
      which the different kinds of mental operations in the processing of face have
      been identified. On the other hand, a lot of studies in neuropsychology have
      analyzed the deficits in visual processing of face, specifically due to lesions
      or dysfunctions of the central nervous system. Finally, research in
      neurophysiology (cellular recording in animal and functional cerebral imagery in
      man) have tried to highlight the complex assembly of cerebral areas implicated in
      these different operations. Besides a short summary of the principal data
      collected in this interdisciplinary approach, we present in this contribution
      results obtained in our laboratory and in the context of an "Action de recherche
      concertee", in the fields of neuropsychology and cerebral functional imagery.

PMID- 14639874
TI  - [Type I diabetes: an enteropathy?].
AB  - In the animal model of type-1 diabetes found in BioBreeding rats, an enteropathy
      characterized by morphological, biochemical and functional features precedes the
      autoimmune insulitis, and both lesions are modulated in their severity by dietary
      factors. Alterations of the intestinal mucin content, of gut permeability and of
      the information transfer between intestinal GLP-1 and its islet receptors, may
      link this enteropathy to the islet pathology.

PMID- 14639875
TI  - [Onecut transcription factors: role in the development of the pancreas and the
      liver].
AB  - The development of the organism involves the formation of tissues that differ by
      the morphology and functions of the cells they contain. This results from the
      synthesis, coordinated in time and space, of a tissue-specific set of proteins.
      Transcription factors, which control gene expression, play a crucial role in this
      process. We have discovered a family of tissue-restricted transcription factors,
      called Onecut, whose prototype is HNF-6 (OC-1) and the two other mammalian
      members are OC-2 and OC-3. During embryogenesis, HNF-6 controls in the endoderm
      the transcription of genes which code for other transcription factors. In this
      way, HNF-6 regulates several developmental programs. To identify these programs,
      we have inactivated the Hnf6 gene in the mouse. This has shown that HNF-6 is a
      key factor in pancreas development and its endocrine differentiation, as well as
      in formation of the biliary tract. The Hnf6-/- mice develop diabetes mellitus and
      cholestasis. The patterns of expression of OC-2 and OC-3 superimpose partially,
      and coincide in part with that of HNF-6. This suggests functional interactions
      between the OC factors during tissue differentiation. We are tackling this
      question by studying the phenotype of mice in which one or several Onecut genes
      have been inactivated.

PMID- 14639876
TI  - Saving millions on prescriptions.

PMID- 14639877
TI  - Preparing for a deposition.

PMID- 14639878
TI  - Just the baby blues?

PMID- 14639879
TI  - Cholesterol absorption inhibitors: a closer look.

PMID- 14639880
TI  - Blood lead screening.

PMID- 14639881
TI  - Evidence-based management of the fibromyalgia patient. In search of optimal
      functioning.

PMID- 14639882
TI  - What lies beneath. Achieving better outcomes in venous ulcer care.

PMID- 14639883
TI  - Trigeminal neuralgia. An overview of diagnosis and treatment.

PMID- 14639884
TI  - Insulin pump therapy. An overview.

PMID- 14639885
TI  - Metabolic syndrome. An introduction to key issues.

PMID- 14639886
TI  - Saving life and limb. Reducing amputations through good foot care.

PMID- 14639888
TI  - Patient information.  Morning sickness.

PMID- 14639887
TI  - Bringing HOPE for diabetes treatment to China.

PMID- 14639889
TI  - Warfarin and herbal supplements. A volatile combination.

PMID- 14639890
TI  - HIV-associated neuropathies. Not a necessary consequence of HIV infection.

PMID- 14639891
TI  - Sticks, stones & slams. How girls use violence to tear each other down.

PMID- 14639892
TI  - A close-up perspective on SARS.

PMID- 14639893
TI  - We need joint action to combat arthritis.

PMID- 14639896
TI  - Weighing up the benefits of remifentanil via PCA.

PMID- 14639899
TI  - A local public-private partnership.

PMID- 14639900
TI  - Hepatitis C: treatment challenges.
AB  - Hepatitis C is a significant public health problem, yet transmission can be
      prevented and the disease is treatable. Nurses have a key role in delivering
      care.

PMID- 14639901
TI  - Multidisciplinary disease management in rheumatology.
AB  - With an increasingly ageing population, the number of patients with
      osteoarthritis and rheumatoid arthritis is expected to rise. High-quality patient
      education and self-management are essential in these chronic debilitating
      conditions. A multidisciplinary team has produced a template to guide the
      assessment, treatment and holistic care of patients in primary care.

PMID- 14639902
TI  - The nurse's role in patient-centred medicines management.
AB  - Nurses in all care settings are crucial to the effective delivery of medicines
      management. This paper argues that adopting a collaborative approach will help
      patients get the most out of their medication and reduce non-compliance. The
      'concordance' approach recognises partnership rather than directorship, and is
      based on arriving at shared agreements.

PMID- 14639903
TI  - Smoking cessation: the case for hospital-based interventions.
AB  - The second paper in our four-part Study series on smoking cessation looks at
      interventions that nurses can use with smokers in hospital. When admitted with an
      illness linked to their smoking, smokers may be at a point in life at which they
      are prepared to consider giving up. Armed with information and specialist
      training, nurses can help them achieve this goal.

PMID- 14639904
TI  - Patient satisfaction with information received after a diagnosis of angina.
AB  - Nurses in one coronary care unit were aware that patients who had experienced an
      episode of angina were not receiving the same amount of information about their
      condition as those who had had a myocardial infarction. This led to the
      development of a questionnaire to determine patient's satisfaction with the
      information they received, with the aim of improving the service.

PMID- 14639905
TI  - The formation of oedema. Part 2: Cellular response to tissue damage.
AB  - Oedema is the body's response to tissue damage due to a range of causes, from
      immobility to heart failure. The second part in our series looks at why it
      occurs, outlines the two main types of oedema and describes the cellular-level
      mechanisms that lead to its formation, including changes in hydrostatic pressure,
      the disruption of nutrient delivery and electrolyte disturbance.

PMID- 14639906
TI  - An introduction to qualitative research concepts for nurses.
AB  - Qualitative methods are increasingly used to explain complex concepts within
      nursing practice. This paper defines qualitative research and offers practical
      advice for getting started and interpreting such research. Phenomenology,
      ethnography and grounded theory are explored briefly, with examples of research
      projects. Data collection and analysis are also discussed.

PMID- 14639907
TI  - Managing obesity in children and adults.

PMID- 14639908
TI  - Empowering people with diabetes helps them make informed choices.
AB  - Empowerment is a key component of the National Service Framework for Diabetes.
      This paper explains the concept and relates it to a major international study of
      the attitudes, wishes and needs of people with diabetes. Drawing on her own
      experience, the author describes the roles of the expert patient and the diabetes
      champion.

PMID- 14639909
TI  - Meeting the National Service Framework Standards for Diabetes.
AB  - Diabetes is not simply a disorder of the metabolism but a chronic disease that
      affects every aspect of a person's body and life and is becoming increasingly
      common This paper outlines the National Service Framework for Diabetes standards
      and how they aim to reduce the incidence and the risks of complications of this
      condition.

PMID- 14639910
TI  - Managing diabetes in the hospital setting: a nurse-patient partnership.
AB  - People with diabetes who are admitted to hospital often experience deterioration
      in their blood glucose levels because of their presenting condition. This paper
      discusses the principles of diabetes control, how hospital admission may affect
      the condition and how nurses can contribute to providing state-of-the-art
      diabetes care.

PMID- 14639911
TI  - Leadership qualities framework provides a useful tool for nurses.
AB  - Good leadership can be difficult to define, but it is vital to inspiring staff to
      improve services. A framework has been developed to enable NHS leaders at all
      levels to assess their strengths and identify their development needs. It is
      applicable to leadership roles at any level, including nurses.

PMID- 14639912
TI  - 'White blood': dose benefits of human milk.

PMID- 14639913
TI  - Protecting breastfeeding: Brazil's story.

PMID- 14639914
TI  - Hands off! The Breastfeeding Best Start project (1).

PMID- 14639915
TI  - 'It's the belief that's important! Interview by Mary Stewart.

PMID- 14639916
TI  - Where there's a Will ... planning for difficult times.

PMID- 14639917
TI  - Family matters: taking a genetic history.

PMID- 14639918
TI  - Non-pharmacological methods of pain relief.

PMID- 14639919
TI  - [Alcoholic liver diseases in Japan and modification by hepatitis virus].
AB  - Recently incidence of alcoholic liver disease (ALD) has been increasing in Japan
      associated with an increase in alcoholic beverage consumption. There have been a
      large number of reports about the relationship between alcohol and
      hepatocarcinogenesis, but it remains controversial. In this review, we addressed
      1) the recent trend in incidence of ALD including severe alcoholic hepatitis
      (SAH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in heavy drinkers
      in Japan, and 2) the characteristics of HCC in heavy drinkers with negative serum
      markers for viral hepatitis. We carried out nation-wide survey by asking for the
      hospitals that are approved by the Japanese Society of Gastroenterology for
      recent aspects of in-patients with ALD. Except for HCC, percentage of ALD without
      viral hepatitis is more than 70%, which is increased when compared to the
      national survey carried out in 1992. Percentage of alcoholic LC without positive
      markers for viral hepatitis was 61% and alcohol plus virus group was 39%.
      Furthermore, in alcoholic LC patients without HCC, those who did not have viral
      hepatitis were 80%. However, the percentage of HCC without viral hepatitis was
      27% of all of the heavy drinkers with HCC. Regarding our own cases, subjects were
      432 HCC patients who were admitted to our hospital since 1995. There were 296
      cases (68.5%) of HCV-positive, 70 cases (16.2%) of HBV-positive, 27 cases (6.3%)
      of both HCV- and HBV-positive. Thirty-nine cases (6.7%) were negative for serum
      markers for viral hepatitis. Among them, 13 cases (3.0%) were not heavy drinkers
      (non-B, non-C, non-alcohol) and 26 cases (6.0%) were heavy drinkers (non-B, non
      C, heavy drinkers). Twenty-five of these 26 (96.2%) cases had cirrhosis. In
      conclusion, since the consumption of alcohol is increasing in Japan, the
      frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral
      hepatitis infection, however, still plays an important role in
      hepatocarcinogenesis in heavy drinkers. Radiographic examinations at an
      appropriate interval for HCC are recommended, even in cases with alcoholic liver
      cirrhosis who are negative for serum markers of viral hepatitis, to ensure the
      early diagnosis of HCC.

PMID- 14639920
TI  - [Ethanol changes sensitivity of Kupffer cells to endotoxin].
AB  - Gut-derived endotoxin plays an important role in alcoholic liver injury.
      Intestinal sterilization with antibiotics (polymyxin B and neomycin) or
      inactivation of Kupffer cells with gadolinium chloride can prevent early alcohol
      induced liver injury in the Tsukamoto-French model. Although short-term
      administration of alcohol enhances endotoxin hepatotoxicity, a majority of
      studies report that short-term ethanol inactivates Kupffer cells. It is therefore
      paradoxical that Kupffer cells are involved in alcoholic liver injury based on in
      vivo data with gadolinium chloride and antibiotics, yet ethanol blunts activation
      of isolated Kupffer cells. Accordingly, this review focuses on understanding this
      paradox by studying the temporal effect of ethanol in vivo on the response of
      subsequently isolated Kupffer cells. Mice were given ethanol intragastrically,
      and LPS was injected later. One hour after ethanol treatment, serum transaminases
      after LPS were 60% of control, while ethanol increased these parameters about 3
      fold 21 hours after ethanol. Pretreatment with antibiotics blocked these effects
      of ethanol. Two hours after ethanol administration, the LPS-induced increases in
      intracellular calcium concentration and TNF alpha release by Kupffer cells was
      diminished by 50% of control, and these parameters were reciprocally enhanced two
      fold at 24 hours. Sterilization of the gut with antibiotics blocked both effects
      of ethanol on intracellular calcium concentration and TNF alpha release. Twenty
      four hours after ethanol, CD14 in Kupffer cells was elevated to about five-fold.
      In Kupffer cells from mice treated with ethanol 1 hour earlier, IRAK expression
      and activity and NF kappa B were decreased to 50-60% of control. In contrast, in
      Kupffer cells from mice treated with ethanol 21 hours earlier, LPS-induced TNF
      alpha production, expression and activity of IRAK were increased 1.5-fold over
      controls, while NF kappa B activation was elevated 3-fold. Kupffer cells isolated
      from rodents early after ethanol exhibited tolerance to LPS, whereas
      sensitization was observed later. In conclusion, acute ethanol alters the
      expression of endotoxin receptors and intracellular signaling molecules, and
      causes both tolerance and sensitization of Kupffer cells to endotoxin. It is
      postulated that tolerance of Kupffer cells contributes to the impairment of
      innate immune system in alcoholism, while sensitization to endotoxin enhances
      progression of alcoholic liver injury.

PMID- 14639921
TI  - [Japanese national survey of adolescent drinking behavior: comparison between
      1996 and 2000 surveys].
AB  - This report shows Japanese adolescent drinking behavior from the national surveys
      conducted in 1996 and 2000. We randomly selected 120 junior high schools and 100
      senior high schools nationwide. We requested the cooperation of the principals of
      these schools and sent questionnaires to each school. Students answered
      anonymously the questionnaires during school time, and sealed in envelopes by
      themselves; then teachers collected the envelopes. The questionnaire focused on
      adolescent drinking behavior. Valid responses numbered 42,798 (1996) and 47,246
      (2000) from the junior high schools and 73,016 (1996) and 59,051 (2000) from the
      senior high schools. The number of students surveyed represented about 1% of all
      Japanese junior high school students, and about 2% of all senior high school
      students. This report covers only students who gave answers on both drinking
      frequency and drinking quantity. It compares adolescent drinking behavior between
      the 1996 and 2000 surveys, such as drinking frequency, drinking quantities,
      drinking occasions, methods of obtaining alcohol, kinds of alcohol drunk, alcohol
      related problems, opinions on the law that prohibits minors under 20 years of age
      from drinking alcohol, and distribution of drinking status of the subjects by the
      Quantity-Frequency Scale (QF scale). In a comparison of adolescent drinking
      behavior between the 1996 survey and 2000 survey, non-drinkers among junior high
      school students increased from 45% to 55%, and those among senior high school
      students increased from 27% to 33%. On the other hand, ratios of female students
      in both junior and senior high schools who drank 1 or more times per week were
      higher in the 2000 survey than in the 1996 survey. Comparison of the 1996 survey
      and 2000 survey did not indicate that Japanese adolescent drinking has increased
      or decreased.

PMID- 14639922
TI  - [Change in body image of patients with alcohol dependence during treatment
      process].
AB  - In order to find useful information for the establishment of new treatment method
      to alcohol dependence, we investigated the change of the body image of patients
      with alcohol dependence before and after the treatment. HABIT (Haga Body Image
      Test), a questionnaire about body image developed in department of psychiatry in
      Kyoto Prefectural University of Medicine, was used to examine the change of body
      image between pre- and post-3-month conventional treatment program in 46 patients
      with alcohol dependence hospitalized into special institutions for treatment of
      the disease in Kyoto. Patients with poor outcome of the treatment showed
      improvement of body image on visceral function, feeling of appetite and outward
      appearance, while patients with good outcome indicated no significant change in
      these aspects. This finding likely suggests that the treatment would result in
      good outcome in patients having stable feeling of physical health, and the
      cognitive treatment approach about these aspects of body image should be
      performed on the patients with poor treatment outcome. On the other hand, the
      body image about motor function showed significantly higher score in the patients
      approach for the patients with poor outcome to become aware of their physical
      activity would be effective.

PMID- 14639923
TI  - [Study of therapeutic community for drug dependence in San Francisco (I)].
AB  - Therapeutic Communities (TC) have played an important role in the recovery from
      drug dependence around the world since the 1960s. They employ multiple and
      comprehensive methods which include community meeting, life training,
      psychoeducation, psychotherapy, medical care, and vocational coordination etc. In
      Japan, there is not such comprehensive rehabilitation programs for drug
      dependence. In order to learn the programs of TCs, we attend the programs of
      Walden house and Asian and American Recovery Services (AARS), which San Francisco
      and rehabilitation programs in Japan and how to introduce the TC methods into
      Japan.

PMID- 14639924
TI  - [A life-long pursuit of liver failure as clinician].

PMID- 14639925
TI  - [The treatment of Helicobacter pylori infection in upper gastrointestinal
      disorders].

PMID- 14639926
TI  - [Helicobacter pylori eradication therapy for extragastrodudenal diseases].

PMID- 14639927
TI  - [A case of type 4 colorectal carcinoma with rapid progression observed
      radiographically].

PMID- 14639928
TI  - [An adult case of midgut volvurus with malrotation diagnosed by MR angiography].

PMID- 14639929
TI  - [A case of acute hepatitis associated with parvovirus B19].

PMID- 14639930
TI  - [A case of early syphilitic hepatitis accompanied by intractable gastric ulcer].

PMID- 14639931
TI  - [A case of intrahepatic biliary papillomatosis associated with autoimmune
      hepatitis].

PMID- 14639932
TI  - [A case of autoimmune pancreatitis occurring during intravesical bacillus
      Calmette Guerin immunotherapy for ureteral cancer].

PMID- 14639933
TI  - [Thinking on the coming psychiatry--what the DSM-diagnosis brought about in our
      psychiatry].
AB  - Since the DSM-III diagnosis has been introduced in our psychiatric practices in
      1980, the mental disorders which have been thought to be of psychological quality
      now came to have the biological basis. This means the rebirth of W. Griesinger's
      concept in which the psychosis is the brain disease. We should say, the mental
      disorders are the brain disease. This movement is a new conservatism. The second
      characteristics are widening of concept "mental disorder". The personality
      disorder is new category which is different from the classical concept of
      psychopathy. Now all psychiatric professors in Japan have recognize the concept
      "borderline personality disorder". This means that the psychiatrist has taken
      over the responsibility about the psychosocial problems from which they had kept
      themselves away in their clinical practices. The third is that the generalized
      anxiety disorder and the social anxiety disorder have been included in the DSM
      diagnosis. These are the borderland concept between the healthy and pathological
      condition which has been thought to belong to the mental health area. These have
      given us, the psychiatrist, the opportunity to think again on what the mental
      soundness really is.

PMID- 14639934
TI  - [Perinatal psychiatry for mother-infant mental health--perinatal care for
      untreated patient].
AB  - I have presented to our support system, which mainly utilizes the Edinburgh
      Postnatal Depression Scale (EPDS) at 4 days and 1 month for mothers in the
      perinatal period and newborn babies, who have been under the care of the Morioka
      Red Cross Hospital. The perinatal system for mothers and babies, which has
      evolved over the past 9 years at the Morioka Red Cross Hospital. I explained the
      case of a 25-year-old woman who had already been suffering from depression before
      her pregnancy, and the course of improvement she experienced under this support
      system. In particular, I have shown a means of support, which can be provided by
      the obstetrics staff and is available to patient and families without making them
      feel hesitant. We take care of childbirth, and after baby care has started, we
      encourage depressive mothers to visit the Psychiatric Department. As a result,
      depression is no longer problematic, and the mothers recover sufficiently to be
      able to take good care of their babies. Even now, we are keeping track of these
      mothers and babies, while working together with the public health centers in
      communities. In the future, we will place emphasis on the implementation of SCID
      and on the careful observations of mothers and especially, babies, under the room
      in system. We are also planning to begin lactation guidance at an earlier stage
      than before.

PMID- 14639935
TI  - [Screening and intervention for depressive mothers of new-born infants].
AB  - BACKGROUND AND THE AIM OF THE STUDY: Postnatal depression is a key concept for
      mother-infant mental health. Evidence of its impact on mother-infant relationship
      has been increasingly demonstrated in recent years. Therefore optimal
      intervention is important for women and their babies' mental health. Identifying
      risk factors of postnatal depression and developing screening system are needed.
      Study I Hospital-based prospective study--onset and course of Postnatal
      depression and developing screening system. SAMPLING AND METHOD: One hundred and
      one consecutive admitted women on maternity ward in our university hospital were
      invited to the study and 88 mothers participated. Present psychiatric status was
      assessed by telephone interview at three weeks and three months postnatally,
      using the Schedule for Affective Disorders and Schizophrenia and diagnosis was
      made based on Research Diagnostic Criteria. The Maternity Blues Scale and
      Edinburgh Postnatal Depression Scale (EPDS) were also administered at the 5th
      day, one and three months postnatally. RESULTS AND DISCUSSION: At 3 weeks, 21 of
      the 88 mothers (24%) were categorized as having had Maternity blues, and twelve
      (14%) were diagnosed as depression cases. At 3 months postpartum overall 15 of 88
      mothers (17%) were categorized as depression cases. Ten out of total 15 mothers
      had their onset of depression within the first week. There were no differences in
      age, parity, educational level, social class compared to non-depressed mothers.
      The scores of the Blues and the EPDS were always significantly higher in
      depressed mothers. The Blues scale score was significantly higher in the
      depressed mothers compared to the control mothers at any timing of investigation.
      Even at the fifth postnatal day, 11 of 15 mothers who subsequently became
      clinical depression had already scored 9 or more, which is indicative of
      postnatal depression, this means postnatal depression could be detected from the
      very early postpartum period. As for the validity test of the EPDS, having set a
      cut-off point being 9 or more, the sensitivity was 82% and the specificity were
      95% respectively. This score is the same as Okano reported in Japan and lower
      than many studies in Western countries. Study II Multi-centre prospective study
      of early postpartum mood states. SAMPLING AND METHODS: Fourteen obstetric wards
      in teaching hospitals participated in the study, and there, recruitment in each
      ward continued until 20 post-natal women had agreed to participate. Two hundred
      twenty six patients (89.7%) completed the study. During the first 5 days
      Maternity blues scale, and the EPDS on the 5th postnatal day, and one month
      postnatally the EPDS again were given to the mothers. The EPDS score of 9 or more
      was regarded as a probable case of postnatal depression. RESULTS AND DISCUSSION:
      Seventy-nine out of the 226 patients (35%) had maternity blues. Forty six out of
      the 226 patients (20%) had postnatal depression (EPDS being 9 or more) at one
      month postnatally. There was a significant correlation between the EPDS scores on
      the 5th postnatal day and those at one month. Having maternity blues and higher
      than 9 or more of the EPDS score were significantly related to the EPDS scores of
      9 or more at one month postnatally. (odds's ratio = 4.4 and 13 respectively).
      Dysphoria on 5 day was significantly related to history of pregnancy loss,
      Caesarean section, Maternal and neonatal complications and Maternity blues.
      Dysphoria on one month was only related to Maternal complication. CONCLUSIONS:
      The onset of postnatal depression can be within the first week after delivery.
      The use of the EPDS during the first week is a simple and useful screening for
      early onset case. Maternal complications and related medical factors might be the
      risk factors of mood disturbance during early postnatal period.

PMID- 14639936
TI  - [Treatment strategy for women with puerperal psychiatric disorders-
      psychopharmaco-therapy and its impact on fetus and breast-fed infants].
AB  - Women have the most possibility of suffering from mental disorders during
      pregnancy and postpartum periods in their whole life time. Especially, postnatal
      depression is not uncommon with an incidence of 10-20%, fortunately a screening
      system has been developed, and in Japan the Edinburgh Postnatal Depression Scale
      (EPDS) is now practically used in both hospitals and community health service
      centers. Additionally most mental disorders during this period are not severely
      disturbed, so they do not have to be necessarily treated by psychiatrists.
      Severely disturbed cases, however, which include postnatal depression with self
      or infant harm thought or puerperal psychosis are to be treated by psychiatrists
      and tend to have psychopharmaco-therapy. In using psychotropic drugs attention
      must be paid for both women and their babies. Impact on breast-fed babies while
      mothers take psychotropic drugs have been reported, mostly as case reports. We
      have reported the controlled studies, (1) The 25 mothers with postnatal
      depression were treated by tricyclic antidepressants, of which 10 breast-fed and
      15 did not. The drugs were amitriptyline, imipramine, clomipramine, dothiepine,
      (2) The 30 mothers with puerperal psychosis were treated by antipsychotic drugs,
      of which 12 breast-fed and 18 did not. The drugs were chlorpromazine,
      trifluoperazine, perphenazine and haloperidol. Both antidepressants and
      neuroleptics were transferred through breast-milk and a few % of maternal dose
      per kilogram were injected to their babies by calculating drug concentration
      ratios of in breast-milk/in serum. None of the breast-fed infants had adverse
      effects, and no developmental difference was found compared to bottle-fed infants
      using the Bayley Development Scale during infancy. Furthermore, the breast-fed
      infants were followed up as long as possible up to 30 months and no significant
      developmental delay was found. In addition, we reported a case study on four
      breast-fed babies whose mothers took fluoxetine. The infants had no adverse
      effects. Pregnant women and their fetuses need to be more carefully monitored.
      Three preliminary cases were reported here; the pregnant women took clomipramine,
      sulpiride, haloperidol and chlorpromazine. Drug concentrations in maternal plasma
      in late pregnancy and postnatally and in umbilical cords were almost the same,
      which meant they were freely transferred from mothers to babies. Regarding the
      neonate's outcome, all were full turn born with normal birth weight with good
      Apgar scores. Weight gain in one month was normal which meant all babies had
      normal sucking without hypotonic muscle. Psychiatrists must accumulate these date
      and contribute as one of specialists in perinatal mental health in multi
      disciplinary team.

PMID- 14639937
TI  - [Motivational conflict, attachment "amae" and emotional communication between
      infants with autistic spectrum disorders and their caregivers].
AB  - To date, many researchers in Japan have been working on the assumption that the
      cause of autistic spectrum disorders is attributable to some disorder in the
      ability of the child. We have been working on the premise that the autistic
      spectrum disorders are brought about by some form of relationship disturbances in
      early infancy, and have been attempting to validate this hypothesis through early
      intervention. We have been examining the developmental process of affective
      communication in infants with autistic spectrum disorders. We postulated approach
      avoidance motivational conflict (Richer, 1993) as the primary factor impeding
      development of affective communication, focusing therapeutic intervention on this
      perspective. As a result, attachment behavior was remarkably improved in the
      children. Through a clinical course of an example, the problem pertaining to the
      process of acquiring the function of language cognition is discussed. Starting
      with the concept that the meaning of any given object is not stipulated as a
      unique existence, but by context, it is pointed out that in order to relate the
      meaning of some object to a child, sharing with the child "which" attributes of
      the object the child should focus upon and "how" it should be dealt with are
      indispensable. This is then followed by discussion of how this cannot be
      accomplished without deepening of affective communication upon the basis of
      attachment formation.

PMID- 14639938
TI  - [Mother-infant mental health from viewpoint of relationship disturbance].
AB  - Infants can adapt themselves and their relationship with their caregivers in a
      way incomparable to any other stage in life. Infants are innately motivated to
      communicate with people and to actively take part in human social interaction.
      The question is how to provide an environment that facilitates such potentials
      for each particular infant and its family. Japan strove to improve the physical
      aspect of maternal and infant care after the second World War and yielded a
      nation-wide perinatal and infant screening system that produced a world minimum
      infant mortality rate and more than 80% compliance rate of infant checkups.
      Instead, infant abuse and infants with development disorders and psychosomatic
      symptoms has alerted the professionals to improve their approach. In addition,
      the increasing incidence of child abuse, juvenile crimes, eating disorders and
      other emotional and behavioral problems of children and adolescents has alerted
      the government and public to reconsider the importance of early intimate
      relationship. Creating a secure base for families to enjoy nurturing
      companionship with their infants is now common goal of infant mental health in
      Japan. As professionals we try to introduce a more dynamic, natural, non
      judgmental empathic approach to support troubled infant care-giving systems.
      Whichever problem an infant may suffer, whether a problem of body or mind, its
      mother is bound to suffer and much more so in Japan with its old values for
      divine motherhood, stigmas associated with abnormality and new demands for
      perfect mothering. It should be acknowledged more and more that a well-meant
      effort on the side of infant workers cannot yield beneficial outcomes for mothers
      and infants unless we take into full account the importance of the complex
      intertwining of diverse factors, including the infant's predisposition, the
      mother's upbringing and past trauma and quality of the attachment system
      supporting the mother and family interaction. It is here that an urgent need to
      introduce infant mental health exists. Health professionals exchange, having
      shown their clinical attitudes and knowledge to their trainees, mutual nurturing
      companionship among workers, infants and families, which is the spirit of infant
      mental health. The dawn of infant mental health is steadily breaking in Japan.

PMID- 14639939
TI  - Implementation of evidence-based treatment for schizophrenic disorders.

PMID- 14639940
TI  - Treatment quality as a crucial issue in the process of closing Como Mental
      Hospital.

PMID- 14639941
TI  - Optimal treatment project for schizophrenia: results from a randomized,
      controlled, longitudinal study.
AB  - This study aimed to compare the clinical and social benefits associated with
      Optimal Case Management (OCM) treatment that employ cognitive-behavioural
      strategies to those associated with Routine Case Management (RCM) that is widely
      used in community health services. Hundred patients with schizophrenia were
      randomly allocated to OCM and RCM treatment conditions. Patients in the OCM
      condition showed significantly more improvement on all measures compared to
      patients in RCM condition. Improvement on clinical symptoms and social
      functioning achieved by OCM tended to show a regular and continuous pattern
      throughout the course of the study. The results of this study suggest that every
      optimal treatment should aim improvement in social functioning and therefore
      quality of life of the patients.

PMID- 14639942
TI  - [Implementation of integrated mental health care in an urban district of Tokyo].
AB  - Japan had a long history of long-term hospital care and is now trying to change
      it into community-based psychiatry. Implementing comprehensive approach that has
      already been proven effective through evidence based data in one particular
      community, one has to overcome several local barriers, if the same approach is to
      be implemented in different situations, such as differences in socio-cultural
      background and health care system. This is a report of the activities of Minato
      Net 21 pointing out the "local barriers" on implementing comprehensive approach
      in an urban district of Tokyo.

PMID- 14639943
TI  - [Recovery of intersubjectivity and empathy in schizophrenics: through a
      characteristic type of friendship "frolicking"].
AB  - The author has noticed a characteristic form of close, frolicsome friendship
      between recovering adolescent schizophrenic patients. It occurs in groups of
      young patients in a psychiatric clinic and in a day-care institution. Through
      this type of friendship, their intersubjectivity, ability for empathy and human
      relations develop, essential changes for the amelioration of schizophrenia. It is
      characterized by 1 A mutual relationship on equal terms with another
      schizophrenic patient of the same sex and generation; particularly close
      friendship between two patients, or sometimes several patients who form a group,
      spending much time together. 2 Playful, childish behavior, jokes and jests;
      Patients laugh and make others laugh, playing together. 3 Touching the friends'
      bodies and coordinated playing such as dancing and singing together. 4 Chatting
      and having common interests, along with sharing various experiences. 5 Enjoyment
      with so much energy that sometimes, as in a gang, social norms are contravened. 6
      Being a transient phenomenon that ends naturally after a certain period. Through
      such friendship, the adolescents show mental growth compared with their premorbid
      state. They come to sympathize with others' feelings and willingly cooperate.
      Their social relationships and spheres of activity expand, and spontaneity and
      self-esteem become improved. They come to assert themselves adequately, tolerate
      stress, and conform to social norms. Moreover, they advance to developing a
      purpose. e.g. work. To be able to have empathy through friendship with those of
      the same sex and generation is a basic developmental theme generally seen in
      childhood and pre-adolescence. Such friendship between the patients studied
      represents benign regression in such a developmental period. This type of
      friendship is characterized by a frolicsome and playful atmosphere. Frolicking by
      means of jokes, jests and body-touching, and play with coordinated acts lead to
      the sharing of emotions and development of their intersubjectivity, the latter
      improving the person's empathy, spontaneity and self-esteem. This type of
      friendship appears in patients in their teens or twenties once a certain period
      has passed after the disappearance of positive symptoms. Its typical course is
      seen in teen-agers who show a premorbid personality deviation such as difficulty
      in establishing social relationships. No particular tendency as to gender or
      family type was found. Therapists should provide the opportunity and setting for
      this type of friendship to develop. Adolescent schizophrenics can gather together
      and are open-mindedly accepted in such a setting, which has an informal component
      where therapeutic staff may not interfere in this playful atmosphere. Therapists
      should act as third persons, once friendly play begins, after the introductory
      period during which the therapists' protection and limits on social stimulation
      are needed. It is desirable to appreciate patients' friendships and self-help,
      offering a rehabilitation program and adequate support, as they step forward to
      the future.

PMID- 14639944
TI  - [Reversible choreoathetosis associated with lithium intoxication].
AB  - Several reports have been published in the literature of choreoathetosis
      associated with lithium intoxication, but little is known about choreoathetosis
      without concurrent antipsychotic treatment. We report a 65-year-old woman with
      lithium intoxication whose choreoathetosis completely recovered without sequela
      following decrease of her serum lithium level. She had been treated elsewhere for
      bipolar II disorder and also for hypertension, chronic hepatitis type C and
      diabetes mellitus. As she became hypomanic, lithium carbonate at 600 mg/day was
      commenced, which was increased to 1200 mg/day due to unfavorable therapeutic
      response. She began to manifest disorientation and abnormal involuntary movement
      and was therefore referred to our Department of Psychiatry. Her clinical symptoms
      at admission included consciousness disturbance with marked bilateral symmetrical
      slow-wave activity in her EEG and choreoathetosis was observed in her face and
      upper and lower extremities. Cerebellar symptoms were minimal with only mild
      ataxic gait and finger-to-nose test did not show dysmetria or intention tremor.
      Her serum lithium level was 3.52 mEq/L, which was clearly in the toxic range. She
      demonstrated no metabolic abnormalities including hyperglycemia, and was
      diagnosed with lithium intoxication and treated with water loading and mannitol
      for forced diuresis. On the 14th day after admission her consciousness
      disturbance and choreoathetosis resolved, but EEG abnormalities still persisted.
      On the 23rd day after admission, she was discharged with clinical remission and
      normal EEG background activity. Although she developed mild renal dysfunction,
      hemodialysis was not indicated. Hypersensitivity of dopamine receptor in the
      nigrostriatal pathways may contribute to choreoathetosis in association with the
      patient's vulnerability. Choreoathetosis can be a sign of lithium intoxication
      and prompt treatment is required following careful differential diagnosis.

PMID- 14639945
TI  - [Cancer immunotherapy targeting WT1].

PMID- 14639947
TI  - [Hepatitis-associated aplastic anemia preceded by a hemophagocytic syndrome-like
      state].
AB  - A 21-year-old man was admitted to our hospital for acute hepatitis of unknown
      cause. His liver function improved with rest, but worsened 2 months later. He
      developed a high fever and pancytopenia. The serum level of cytokines including
      TNF-alpha, IFN-gamma, IL-6, and M-CSF was elevated, and hemophagocytes were seen
      in bone marrow. These findings suggested a hemophagocytic syndrome-like state.
      With prednisolone, gamma-globulin, and G-CSF, the high fever disappeared and the
      patient's liver function gradually recovered. However, the severe pancytopenia
      persisted. The bone marrow became acellular with a small number of
      hemophagocytes, and hepatitis-associated aplastic anemia was diagnosed. After
      immunosuppressive therapy with ATG, CyA and G-CSF was started, and the patient
      showed hematopoietic reconstitution. The bone marrow CD4+/CD8+ lymphocyte ratio
      recovered to within the normal range, and the serum cytokines including TNF-alpha
      and IFN-gamma decreased. The increase in serum cytokines, particularly TNF-alpha
      and INF-gamma, as well as the presence of activated T cells associated with the
      preceding hemophagocytic syndrome-like state may have predisposed this patient to
      aplastic anemia.

PMID- 14639946
TI  - [Treatment outcome of myelodysplastic syndrome patients younger than 60 years
      old].
AB  - We evaluated the clinical outcome of 92 patients younger than 60 years who were
      treated between January 1987 and May 2003. Low, Int-1, Int-2 and High risk groups
      categorized by IPSS consisted of 7, 34, 24 and 27 patients, respectively. There
      was no significant difference in the overall survival between 30 patients who
      received allogeneic stem cell transplantation and 62 patients who did not.
      Allogeneic stem cell transplantation provided significantly better outcomes in
      the Int-2 and the High risk groups. Risk factors for overall survival were age
      and disease status at transplantation. Acute and chronic GVHD did not influence
      the relapse free survival rate. Allogeneic stem cell transplantation is a
      curative therapy for MDS. It is necessary to reduce transplantation related death
      and to perform stem cell transplantation as soon as possible for patients with
      Int-2 or High risk of IPSS.

PMID- 14639948
TI  - [Intensive multi-drug chemotherapy for acute myeloid leukemia in a renal
      allograft recipient].
AB  - A Fifty-two year old male, who had received a renal transplantation from his
      sibling 14 years previously, was referred to our hospital because of
      leukocytosis, anemia and thrombocytopenia. A bone marrow examination revealed an
      increase of leukemic blasts with morphological dysplasia of mature hematopoietic
      cells. The diagnosis of acute myeloid leukemia (AML) with multilineage dysplasia
      without antecedent myelodysplastic syndrome was made. Since the patient's general
      condition and the function of the transplanted kidney were well maintained,
      intensive therapy for his AML was chosen. The dosage of the immune suppressive
      reagents that were administered to prevent the rejection of the transplanted
      kidney were reduced during chemotherapy to minimize the adverse effect of immune
      suppression, and G-CSF was administrated to shorten the neutropenic period. Along
      with these supportive strategies, cytosine arabinoside and idarubicin-based
      induction therapy followed by four courses of intensive consolidation therapy
      were successfully performed without disturbing his renal function. It is
      suggested that intensive chemotherapy is feasible for post-transplant AML
      patients when their general condition and transplanted renal functions are well
      maintained.

PMID- 14639949
TI  - [Episodic angioedema associated with eosinophilia in relapsing erythema and
      swelling of the right thigh].
AB  - On March 16, 2000, a 37-year-old male was admitted to another hospital for fever,
      erythema of the limbs, and swelling of the right lower leg. The leukocyte count
      was 19,800/microliter, and the ratio of eosinophils was 61%, suggesting marked
      eosinophilia. Thoracic computed tomography (CT) revealed pneumonia in the left
      lung. However, the patient was negative for autoantibodies or parasitic
      antibodies. Administration of prednisolone at 80 mg/day resulted in a marked
      improvement of the symptoms and the eosinophilia. For diagnosis, detailed
      examination, and treatment, the patient was referred and admitted to our
      department on March 28. The dose of prednisolone was gradually decreased. On
      April 15, the agent was discontinued. Eosinophilia was not observed, however
      erythema of the limbs and swelling of the right lower leg recurred. Skin biopsy
      revealed in mild edema of the corium and eosinophilic infiltration, suggesting
      episodic angioedema associated with eosinophilia (EAE). In 1984, Greich et al.
      reported 4 patients with repeated angioedema, hives, and marked eosinophilia, and
      proposed the term EAE. Since then, more than 50 patients have been reported in
      Japan. Only 4 of these patients were males. We report on the present male patient
      together with the pathological findings.

PMID- 14639951
TI  - [Acute lymphoblastic leukemia with invasive fungal infection causing complete
      atrioventricular block].
AB  - A 62-year-old female was diagnosed as having acute lymphocytic leukemia in
      October 2001. She achieved complete remission after induction therapy with L
      asparaginase, doxorubicin, vincristine and prednisolone. However, an invasive
      fungal infection developed in the lung, followed by a sudden complete
      atrioventricular block. Her heart rate was brought back to normal by the
      administration of isoproterenol. In spite of anti-fungal therapies, the patient
      finally succumbed to pneumonia in January 2002. Autopsy revealed an invasion of
      fungi into the lung, mitral valves and atrioventricular node. We need to pay
      attention to such a cardiac complication when an immunocompromised host suffers
      from an invasive fungal infection.

PMID- 14639950
TI  - [Systemic infection of Aspergillus flavus in a patient with acute lymphoblastic
      leukemia].
AB  - A 57-year-old woman with acute lymphoblastic leukemia (ALL) developed an
      antibiotics-resistant fever after remission induction therapy. Chest X-ray and
      computed tomography scan revealed multiple consolidations and cavities.
      Successively, numerous subcutaneous nodules and a thyroid mass emerged.
      Aspergillus flavus (A. flavus) was cultured from both sites. Despite the
      patient's granulocyte recovery, the fever persisted and multiorgan function
      deteriorated rapidly. However, she was successfully treated with intensive
      supportive therapy including continuous hemodialysis and filtration. Prolonged
      use of amphoterin B and itraconazole failed to cure her aspergillosis, but the
      illness remained indolent thereafter.

PMID- 14639952
TI  - [Invasive pulmonary aspergillosis complicated by complete atrioventricular block
      and aspergillus pericarditis after induction chemotherapy in a patient with acute
      lymphoblastic leukemia].
AB  - A 50-year-old man developed invasive pulmonary aspergillosis after induction
      chemotherapy for acute lymphoblastic leukemia. He was treated with 5
      fluorocytosine and intravenous amphotericin B (AMPH-B). During antifungal
      therapy, he developed aspergillus pericarditis and complete atrioventricular (A
      V) block. The pericardial effusion was decreased and the A-V block was improved
      after treatment with intravenous and intrapericardial instillation of AMPH-B.
      Because the patient's renal function deteriorated, AMPH-B was replaced with
      itraconazol after the latex agglutination (LA) test for an aspergillus-specific
      antigen showed a negative result. The patient, however, died from disseminated
      aspergillosis. Aspergillus DNA was detected in retrospective analysis of the
      serum which had been negative with the LA test. This case indicates that LA is
      not sufficient for diagnosis and post therapy evaluation of invasive
      aspergillosis. PCR or other methods should be used concomitantly with LA.
      Intrapericardial instillation of AMPH-B might be effective for patients with
      aspergillus pericarditis in whom surgical treatment is not indicated.

PMID- 14639953
TI  - [Chronic myelogenous leukemia in a lymphoblastic crisis complicated with deep
      venous thrombosis successfully treated by thromboembolectomy].
AB  - A 20-year-old man was referred to our hospital because of leukocytosis and was
      diagnosed as having chronic myelogenous leukemia in lymphoblastic crisis. His
      left leg began to swell soon after the beginning of induction chemotherapy and
      deep vein thrombosis (DVT) was confirmed by doppler echography, which progressed
      to compartment syndrome next day. After placing a venous filter in the inferior
      vena cava, the patient successfully underwent thromboembolectomy. Venous
      congestion due to massive lymphadenopathy enlarged kidneys, and a hypercoagulable
      condition due to the rapid destruction of leukemic cells may have contributed to
      the formation of the thrombus. This case demonstrates the importance of
      aggressive surgical intervention for severe DVT in patients with leukemia.

PMID- 14639954
TI  - [Three cases of idiopathic thrombocytopenic purpura showing an increase in the
      platelet count following clarithromycin treatment].
AB  - Macrolides have immuno-modulatory effects as well as anti-bacterial effects. We
      successfully treated three idiopathic thrombocytopenic purpura (ITP) patients
      with clarithromycin (CAM). Case 1: A 69-year-old male ITP patient was treated
      with CAM at a dose of 400 mg/day. His platelet count increased from 5.6 x
      10(4)/microliter to 10.1 x 10(4)/microliter. Case 2: A 72-year-old male ITP
      patient was treated with CAM at the same dose. The platelet count increased from
      1.3 x 10(4)/microliter to 12.3 x 10(4)/microliter. Case 3: A 68-year-old female
      ITP patient was treated with CAM at the same dose. The platelet count increased
      from 2.3 x 10(4)/microliter to 13 x 10(4)/microliter. These facts suggest that
      CAM is useful in the treatment of ITP.

PMID- 14639955
TI  - [The necessity of educating the science of nursing for physician: for the purpose
      of medical care with humanity and speciality].

PMID- 14639956
TI  - [Cognitive function as the factor determining higher-level competence in
      community-dwelling elderly: comprehensive health examination for the community
      elderly for the prevention of the geriatric syndrome and a bed-ridden state
      ("otasha-kenshin")].
AB  - PURPOSE: This study was conducted to examine age-related differences in cognitive
      function, and their relation to higher-level competence of elderly living in an
      urban community. METHOD: Participants were 438 individuals (males 168, females
      270) aged 70 to 84 years living in an urban community in Tokyo. Three cognitive
      performance tests, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit
      Symbol, Word Fluency Test, and the WAIS-R Digit Span, were employed for
      estimating cognitive function, and the TMIG Index of Competence for measuring
      higher-level competence. In the Index, three constructions: "Instrumental Self
      Maintenance", "Intellectual Activity", and "Social Role" were involved. RESULTS
      AND CONCLUSIONS: Age-related differences in the cognitive tests were analyzed
      using ANCOVA controlling for educational year. Age-related differences between
      younger elderly (70-79 years old) and older elderly (80-84 years old) were
      observed with the WAIS-R Digit Symbol, Word Fluency Test and the WAIS-R Digit
      Span. The results indicate that information processing speed, executive function
      and primary memory in community-dwelling elderly continue to decline in old age,
      and this trend is salient in the old-old. We carried out partial correlation
      analysis and multiple regression analysis for exploring the relationships between
      cognitive function and the sub-scales in the TMIG Index of Competence,
      controlling for age and educational year. Cognitive function was significantly
      and positively related with the sub-scales in the Index, this being especially
      robust for "Intellectual Activity". The results suggest that higher-level
      competence can be modestly determined with reference to cognitive function, and
      "Intellectual Activity" may have a stronger relation with cognitive function than
      the other two sub-scales in the Index.

PMID- 14639957
TI  - [Changes in community health and welfare services with introduction of the long
      term care insurance system in Japan].
AB  - OBJECTIVE: In Japan, a long-term care insurance system for elderly people was
      introduced in April, 2000. We have conducted a survey using a questionnaire in
      order to explore consequent changes in community health and welfare services.
      METHODS: We sent questionnaires to all municipal governments (671 cities, 1,991
      towns, 567 villages and 23 wards) in Japan in November, 2001, and obtained
      replies from 441 cities (response rate: 65.7%), 800 towns (40.2%), 197 villages
      (34.9%), and 16 wards (69.6%). The questionnaire included questions concerning
      the budget and manpower for community health and welfare services, the state of
      the long term care insurance system, and the activities of public health nurses.
      RESULTS: A total of 57% of all municipal governments was found to be carrying out
      the long term care insurance program in collaboration with other governments. In
      order to clarify the changes in welfare services for elderly people from the
      budgetary viewpoint, we calculated the ratios of the 2000 and 2001 fiscal budgets
      applied for welfare services for elderly people, in comparison with the 1999
      fiscal year. The budgets for elderly people declined to about 40% in 2000 and
      2001 compared with 1999, since the budget for care services was transferred to
      the account of the long term care insurance system. The activities of public
      health nurses employed by municipal governments were not affected by the
      introduction of long term care insurance system. About 80% of all municipal
      governments suggested that both the amounts of care services received by each
      elderly people and the number of elderly people who received care services were
      increasing, and about 70% indicated that the quality of care services was
      improved with introduction of the long term care insurance system. DISCUSSION:
      Most municipal governments consider that introduction of the long term care
      insurance system has had a good influence on community health and welfare
      services. Moreover, our results suggest that the long term care insurance has a
      beneficial impact on care services themselves.

PMID- 14639958
TI  - [Characteristics of social activity of the elderly who belong to senior
      citizens].
AB  - PURPOSE: The purpose of this study was to clarify environmental conditions
      determining the social activities of the elderly, by analyzing levels of activity
      in individuals belonging to clubs for senior citizens. METHODS: In 1998, we
      conducted a survey of over 10,000 elderly subjects, 65 years of age or older, who
      belonged to 228 clubs for senior citizens in a region of Saitama Prefecture,
      using a 'Check list' developed for self-evaluation of social activities. The
      proportions of 'active' and 'inactive' seniors, as judged by the 'Check list' for
      each of the four different aspects of social activities (1. individual
      activities, 2. social participation/volunteering, 3. education/training, 4.
      employment), were compared with those of the standard elderly population.
      RESULTS: Two hundred and seven clubs for senior citizens (90.8%) participated in
      this study. About 82.0% of the members of each club filled out the 'Check list'.
      High levels as compared to the standard population were demonstrated for two
      aspects of social activity: individual activity and social
      participation/volunteering. Women had higher levels of both types of social
      activity than men. Men aged 74 years or younger had lower than average levels for
      three aspects of social activity: social participation/volunteering,
      education/training, and employment. Members who resided in urban areas with easy
      access had higher levels of individual activity, social
      participation/volunteering and education/training. On the other hand, those
      residing in suburbs with large spaces for agriculture had higher levels for
      employment. CONCLUSION: Our results for social activities of elderly subjects
      belonging to clubs for senior citizens indicate that strong correlations exist
      with environmental conditions, including communication facilities and local or
      industrial structure.

PMID- 14639959
TI  - [Analysis of factors determining transfusion albumin usage in different
      prefectures].
AB  - OBJECTIVE: According to recent changes in the prevalence of diseases and
      innovations in medical technology, the requirement for blood products and blood
      plasma fractions has increased dramatically in Japan. The difficulty in meeting
      demands is making resort to importation of blood products from other countries
      necessary. Hokkaido, the prefecture with the highest consumption of blood
      products, uses 10 times more albumin than that of the lowest blood consumer,
      Kouchi, This study analyzed the factors, underlying these differences in albumin
      consumption between prefectures, to provide pointers to meet most appropriately
      blood products utilization. METHOD: The questionnaire regarding management of
      blood products, total amount of consumption of blood products, sex, age and
      diagnosis of patients, examinations of albumin concentrations in the blood before
      and after the use of albumin product, operations etc. was distributed to 8,334
      medical institutes, collected and analyzed. We divided all 47 prefectures into 4
      groups, according to albumin consumption amount, and compared factors for 45-84
      year old patients. RESULTS: The results showed the proportion of patients with
      the top 20 diseases to be significantly higher in the highest albumin consumer
      group than in the others. In addition, the percentage of non-examinations of
      albumin concentrations in the serum before and after the use of albumin products
      was significantly higher in the highest albumin consumer group. Furthermore, the
      concentrations of albumin in the serum both before and after their application
      were significantly higher in the highest albumin consumer group than in the
      others. There was no significant difference in bed usage among the groups.
      Comparison of the results for the 4 groups indicated that the use of albumin in
      cases of liver fibrosis, cirrhosis, hepatoma and gastric cancer may have a
      special impact on the total consumption of albumin per person. Albumin may be
      used in the highest albumin consumer group without sufficient consideration for
      the shortage of albumin products. CONCLUSIONS: There are some factors causing
      difference in albumin consumption among prefectures, such as whether or not
      albumin concentrations in the blood are examined before and after the usage, The
      importance of adopting measures to assure appropriate consumption of albumin
      clearly needs to be emphasized.

PMID- 14639960
TI  - [Association of flatfoot with pain, fatigue and obesity in Japanese over
      sixties].
AB  - PURPOSE: There is still uncertainty whether flatfoot, characterized by lower
      height of the medial longitudinal arch of the foot, is associated with foot
      symptoms in adults. Furthermore, few studies have been conducted to examine any
      association with obesity in older people. In this study, we therefore assessed
      the prevalence of flatfoot among community-dwelling older men and women using a
      footprint method, and analyzed relationships with foot symptoms and obesity.
      METHODS: The study sample consisted of 242 women and 98 men aged 60 years or
      older who were neither institutionalized nor disabled in activities of daily
      living. We collected footprints of both feet, data on weight and height, and
      information on foot symptoms and daily activity. From the footprints, we
      identified the H line by connecting the tip of the second toe and the
      intersection of the internal surface tangent of the foot and the external one.
      Then flatfoot was defined as concavity of the medial arch situated medial to the
      H line in either foot. Foot symptoms (pain and fatigue) were assessed using a 3
      scale questionnaire: no pain (fatigue); present only when walking or standing; or
      present anytime. If present, the place of the pain or the fatigue was further
      identified. We analyzed associations with these symptoms and also with obesity
      assessed in terms of the body mass index (BMI). RESULTS: We identified flatfoot
      in 26.5% (95% Confidence Interval: 22.0-31.0) of the men and 25.7% (95%
      Confidence Interval: 20.2-31.2) of the women. In both sexes, the affected
      individuals had a higher prevalence of foot pain and fatigue than those
      unaffected. The association with the latter in women was particularly
      significant. There was a linear association between prevalence of flatfoot with
      the BMI category in women. In addition, the prevalence was lowest in the least
      obese category in men although this did not reach statistical significance.
      CONCLUSIONS: Flatfoot was significantly associated with the presence of pain and
      fatigue in women. Furthermore, a significant positive association with obesity
      was noted.

PMID- 14639961
TI  - [Functional characteristics of pharmacy services related to home care--results
      from two pharmaceutical association surveys in suburban and old town areas].
AB  - In order to investigate the implementation about pharmacy services focusing on
      home care and to identify differences in functional characteristics in accordance
      with pharmacy location, questionnaire surveys were conducted on all 75 pharmacies
      belonging to T-City Pharmaceutical Association in a suburban area and on all 161
      belonging to K-Ward Pharmaceutical Association in a central downtown district.
      Using data, a principal component analysis was performed. The following services
      were investigated: medication guidance for patients and their families; provision
      of drug information to patients; management of patients' drug history;
      dispensing; advice to physicians; inquiries; management of prescriptions for home
      infusion services; sales of items such as over-the-counter [OTC] drugs
      [commercially available drugs that do not require a physician's prescription];
      display and catalogue sales of nursing items; consultation on home care; holding
      events such as health education programs; guidance for drug management by home
      visits; and information exchange with other medical professionals and social
      workers. The results of these surveys were as follows. (1) The following services
      were regularly performed in both urban and suburban areas: medication guidance
      for patients and their families; provision drug information to patients;
      management of patients' drug history; dispensing; advice to physicians;
      inquiries; and sales of OTC drugs. (2) The following services were not
      difficiently regularly performed in both areas: display and catalogue sales of
      nursing items; consultation on home care; holding events such as health education
      programs; guidance for drug management by home visits; and information exchange.
      (3) As to principal component analysis, pharmacy functions were divided into 3
      components and the dispensing service strongly influenced the functional
      characteristics in T-City. Whereas, in K-Ward, pharmacy functions were divided
      into 4 components and consultation and information exchange were strong
      influences. (4) Home care-relate pharmacy services were closely associated with
      information exchange on both areas. This implies that enforcing information
      exchange among pharmacists and other health practitioners and social welfare
      practitioners is an essential factor to expand implementation of home-care
      related pharmacy services.

PMID- 14639962
TI  - [Path-analysis model of lifestyle factors and subjective health: the Healthy
      Japan 21 questionnaire survey in Obihiro].
AB  - PURPOSE: The purpose of this study was to determine health problems of citizens
      of the city of Obihiro with reference to the Healthy Japan 21 plan. METHOD: The
      subjects were a total of 2,000 men and women (6-74 years old) who were selected
      at random from the resident ledger of Obihiro. The questionnaire included the 6
      fields (nutrient intake/dietary habits, physical activity/exercise, rest/mental
      health, tobacco, alcohol, dental health) of Healthy Japan 21. The path-analysis
      model was used by sex, in order to examine the relationship between lifestyle
      factors (dietary habits, restful sleep, stress, smoking habits, alcohol intake)
      and subjective health. RESULTS: A total of 979 subjects (49.0%) responded. The
      items that showed a higher proportion than for all Japan were as follows: the
      proportions of persons who felt stress, required a drug or alcohol to sleep,
      drank heavily, and were female smokers. In questions about the harm caused to
      health by smoking, the following items showed lower awareness than deserved:
      bronchitis, gastric ulcer, problems with regard to pregnancy, and periodontitis.
      The following characteristics were found in the path-analysis: 1) If sleep rest
      is sufficient, subjective health is unaffected by stress in men and women; 2)
      Smoking affects dietary habits in men and women, especially in the latter; 3)
      Heavy smoking affects subjective health in men and women independent of whether
      dietary habits are good; 4) There is a positive relation between drinking and
      subjective health in women. CONCLUSION: This study showed that stress and smoking
      are problems for the health of citizens of the city of Obihiro, and suggested
      that the best measure to counter stress is sufficient sleep, while to counter
      smoking spread of knowledge about the harm to health caused by smoking is best.

PMID- 14639963
TI  - [Airborne concentrations of fungal and indoor air pollutants in dwellings in
      Nagoya, Japan].
AB  - PURPOSE: The purpose of this study was to determine airborne fungal
      concentrations in dwellings and to evaluate the relationship between indoor air
      concentrations of fungi and those of indoor air pollutants, temperature and
      relative humidity. METHODS: Indoor and outdoor concentrations of total fungi,
      xerophiles (xerophilic fungi), indoor air pollutants such as formaldehyde,
      nitrogen dioxide, carbon dioxide, carbon monoxide, temperature and relative
      humidity were measured in 54 dwellings in Nagoya, Japan. This study was performed
      in summer and winter from 1995 to 1998. The airborne fungal concentrations were
      analyzed using a pinhole air sampler and dichloran 18% glycerol agar (DG18), and
      compared with the levels assessed with potato dextrose agar (PDA). RESULTS: 1.
      DG18 can be recommended as an excellent medium for determining viable fungi
      concentrations in indoor air. 2. In indoor air, geometric means of total fungal
      and xerophile concentrations in summer were 237-301 CFU/m3 and 24.1-26.8 CFU/m3,
      as compared to 78.7-87.5 CFU/m3 and 18.2-29.5 CFU/m3, respectively, in winter. In
      outdoor air, geometric means of total fungal and xerophile concentrations in
      summer were 208 CFU/m3 and 9.2 CFU/m3, and 72.7 CFU/m3 and 10.1 CFU/m3,
      respectively, in winter. 3. The predominant genera in indoor and outdoor air were
      Cladosporium spp., followed by Penicillium spp. and Aspergillus spp. The major
      Aspergillus spp. was A. restrictus. 4. Indoor as well as outdoor air
      concentrations of total fungi were significantly higher in summer than in winter
      (P < 0.01), whereas differences in total fungal concentrations between indoor and
      outdoor air were not. Airborne xerophile concentrations in summer and winter were
      significantly higher in indoor air than in outdoor air (P < 0.01), while indoor
      as well as outdoor air xerophile concentrations in summer were similar to those
      in winter. 5. The total fungal and xerophile concentrations were not dependent on
      dwelling factors such as the type of dwellings, the type of flooring materials
      and the use of air-conditioners and/or heaters. 6. The total fungal and xerophile
      concentrations were not significantly correlated with the concentrations of all
      the indoor air pollutants. In winter, the total fungal and xerophile
      concentrations significantly increased in proportion to the average relative
      humidity (P < 0.01). CONCLUSION: The total fungal concentrations in indoor air
      were significantly correlated with those in outdoor air, while xerophile
      concentrations were not. The indoor air concentrations of total fungi and
      xerophiles were not dependent on those of indoor air pollutants.

PMID- 14639964
TI  - [The molecular mechanism for lysosome biogenesis].

PMID- 14639965
TI  - [Nutrition and medicine].

PMID- 14639966
TI  - Comparative study on the effects of ointments of tinidazole, hydrocortisone and
      clobetasol on animal models for inflammatory dermatitis in mice.
AB  - To understand further the possible clinical effects of tinidazole ointment at
      relatively high concentration (2%) for atopic dermatitis (AD), we performed a
      comparative study with readily available topical corticosteroids, clobetasol
      propionate (0.005 or 0.05%) and hydrocorotisone butyrate (0.1%) (hereafter
      referred as clobetasol and hydrocortisone, respectively), on inflammatory
      dermatitis in mice. We also observed the effects of combined application of
      tinidazole with clobetasol (0.005%, one tenth of the clinical use) in comparison
      with tinidazole itself, clobetasol (0.05%) or hydrocortisone (0.1%) on the animal
      model. All ointments suppressed inflammatory dermatitis induced by
      trinitrochlorobenzen (TNCB) or oxazolone. The rank order of the potency to
      suppress the ear edema was clobetasol (0.05%), tinidazole (2%) with clobetasol
      (0.005%) > clobetasol (0.005%) > tinidazole (2%) in TNCB-induced dermatitis, and
      hydrocortisone (0.1%), clobetasol (0.05%) > tinidazole (2%), tinidazole with
      clobetasol (0.005%) > clobetasol (0.005%) in case of oxazolone-induced
      dermatitis. We confirmed that tinidazole (2%) suppresses immediate and late phase
      reactions in mice passively sensitized with anti-DNP IgE Mab. In addition,
      tinidazole (2%) was much more potent than hydrocortisone (0.1%) in suppressing
      the amount of scratching, presumably due to itching, in passively sensitized
      mice. These results indicate that the advantage of using ointments of tinidazole
      would be that it has stronger anti-itching effects than corticosteroids.

PMID- 14639967
TI  - The personal digital assistant and its future in nursing.

PMID- 14639968
TI  - CNS or NP debate: the need for a blended advanced practice nursing role.

PMID- 14639969
TI  - Teaching nursing students to teach: creative student instruction.

PMID- 14639970
TI  - The buck stops here.

PMID- 14639971
TI  - Balancing act.

PMID- 14639972
TI  - Too much too young.

PMID- 14639973
TI  - Make a difference.

PMID- 14639974
TI  - Encountering death.

PMID- 14639975
TI  - Highs and lows.

PMID- 14639976
TI  - Unsocial behaviour.

PMID- 14639977
TI  - Older nurses and employment decisions.
AB  - AIM: To investigate the options, decisions and outcomes for nurses aged over 50
      in terms of remaining in, retiring from, or returning to, work in the NHS.
      METHOD: Interviews were conducted with 18 employers, advisers and policy makers
      linked to the nursing labour market. They were conducted by telephone (n = 14) or
      face to face (n = 4), recorded (with consent), transcribed and analysed
      thematically. Interviews were also held with 84 older nurses who were remaining
      in nursing, had retired or had returned to nursing. One focus group was held with
      older nurses who 'remained' in Scotland (n = 11) and the rest of the data were
      collected in face-to-face and telephone interviews (n = 73). Again, interviews
      were recorded (with consent), transcribed and analysed thematically. RESULTS:
      There is a gap between the rhetoric of policy and the implementation of practice
      in the employment of older nurses. CONCLUSION: Older nurses could continue to
      make a valuable contribution to the NHS, especially in light of the shortage of
      nurses, but their value is not always recognised. If older nurses are to continue
      making a contribution then they need good advice about employment, retirement and
      pension options.

PMID- 14639978
TI  - Intuition and practice.
AB  - Intuition is a quality that nurses have traditionally valued, but one that in
      today's evidence-based research climate is often denigrated. Because it is
      difficult to investigate and quantify, intuition has tended to be seen as
      unreliable, unscientific and unsuitable for nursing practice. However, the author
      argues that intuition, like caring, cannot be subjected to measurement and should
      not be overlooked as an important tool.

PMID- 14639979
TI  - Haemostasis, anticoagulants and fibrinolysis.
AB  - Anticoagulant and fibrinolytic drugs are being used with increasing frequency in
      acute and community settings. Nurses need to maintain an up-to-date understanding
      of these drugs to provide effective patient care and education.

PMID- 14639980
TI  - Get ready for the front line.

PMID- 14639981
TI  - Change for the better.

PMID- 14639982
TI  - First contact care. An executive's view.

PMID- 14639985
TI  - Cardiac bypass without the pump.

PMID- 14639986
TI  - Is it morning sickness--or something worse?

PMID- 14639987
TI  - Bedside tracheostomy: a step by step guide.

PMID- 14639988
TI  - Nurse as patient. My road to recovery.

PMID- 14639989
TI  - 2003 earnings survey. The outlook is bright.

PMID- 14639990
TI  - How to overcome a language barrier.

PMID- 14639991
TI  - Is your patient a diabetic? Watch that insulin dose!

PMID- 14639992
TI  - [Experiences in introducing and using a patient data management system (PDMS). in
      anesthesiology at the Clinic of Anesthesiology and Intensive Care Medicine of the
      University of Leipzig].
AB  - In the field of anaesthesia the demands on the quality and quantity of
      documentation are increasing constantly. Patient Data Management Systems (PDMS)
      have proved an effective means of handling the volume of data generated. The main
      reasons for introducing a PDMS vary greatly, nevertheless, it is possible to
      formulate general requirements such as those of the "Position Paper of the Study
      Group on Patient Data Management Systems (PDMS) of the University Departments of
      Anaesthesiology in Bavaria". Although these requirements are very broad, they
      provide a good basis for comparing different approaches to computer-assisted
      documentation in anaesthesiology. The stage currently reached at the Department
      of Anaesthesiology and Intensive Care Medicine (KAI) of the University of Leipzig
      is analysed in comparison with the position paper. The COPRA system was
      established at KAI Leipzig eight years ago. It was developed from an existing
      version for intensive care medicine. It meets the demands made on it when it was
      introduced and can be enlarged and adjusted to the special needs of
      anaesthesiology. One particular requirement was that it should be possible to
      handle computer-assisted documentation and conventional documentation on paper
      simultaneously. This requirement is met by making the printed forms and those
      shown on the VDU practically the same in appearance. The anaesthetist is able to
      recognize "his" record on the screen. This greatly reduces the time required for
      familiarization and training. If possible, the orientation and updating of the
      system should be in the hands of an anaesthetist, since this is the only way to
      ensure that it remains geared primarily to medical needs. Administrative aspects
      have to be taken into account, but they should not dominate the system. The
      anaesthetist managing the system should have some basic training in EDP, or at
      least take a special interest in it. This ensures that minor enlargements can be
      carried out easily, as soon as required. Proper, expert evaluation of the
      compiled data requires both a knowledge of medicine and anaesthesiology and an
      understanding of how information is presented in an EDP system. Enlargements of
      the system resulting from increasing documentation obligations and quality
      assurance can be integrated smoothly. In its current form the system is able to
      depict all parts of the specialist field with the same user interface. By
      systematically meeting general requirements and taking the special needs of a
      hospital into account, it has been possible to create a flexible electronic
      documentation system covering all areas of the anaesthetist's work.

PMID- 14639993
TI  - [Is fiber optic hepatovenous oximetry useful in patients undergoing elective
      partial liver resection?].
AB  - The validity of continuous measurement of hepatic venous oxygen saturation using
      a fibreoptic technique was investigated and set in correlation with intermittent
      measurements of saturation in hepatic venous blood in patients undergoing
      elective partial liver resection (pLR). Eleven patients (4 m/7 f, average age:
      62.6 +/- 11.6 years) were included in the study after approval by the Ethics
      Committee of the University of Leipzig. A fibre-optic heparinized flow-directed
      pulmonary catheter (5.5-F) was inserted through the right internal jugular vein
      into the hepatic vein after induction of balanced anaesthesia
      (isoflurane/alfentanil). The position of the tip of the catheter was verified by
      fluoroscopic guidance. The oxygen saturation in the hepatic vein measured by the
      fibre-optic method and by blood-gas analysis (ShvO2) was compared at nine defined
      measuring points after in-vivo calibration (baseline). The ShvO2 decreased
      nonsignificantly from 84.4 +/- 10.4% to 77.1 +/- 19.1% during occlusion of the
      vessels in the liver hilus (Pringle's manoeuvre). The ShvO2 measured by the fibre
      optic method and by blood-gas analysis correlated well (r = 0.815, p < 0.001).
      The limitations of the method result from artefacts based on surgical
      manipulations in the portal region (compression of hepatic veins, luxation of the
      liver). These artefacts can be differentiated by analysis of the pressure curves
      in the hepatic vein. Nevertheless, fibreoptic hepatovenous oxymetry seems to be a
      feasible method for continuous monitoring of the ShvO2 under intraoperative
      conditions in patients undergoing partial liver resection. Ischaemic situations
      of the liver can be detected and treated early. Additional information can be
      obtained from analyses of parameters in the hepatovenous blood.

PMID- 14639994
TI  - [Acceleromyography registration of the course of neuromuscular blockade of the
      adductor pollicis muscle using monoaxial and biaxial sensors].

PMID- 14639995
TI  - [Lentiviruses to use].

PMID- 14639996
TI  - [Acarbose--an effective drug for the prevention of type 2 diabetes and
      cardiovascular diseases?].

PMID- 14639997
TI  - [Duodecim journal even more electronic].

PMID- 14639998
TI  - [Exercise as a cardiovascular drug].

PMID- 14639999
TI  - [Fainting].

PMID- 14640000
TI  - [Support programs for family caregivers of the elderly].

PMID- 14640002
TI  - [Reduction of involuntary seclusions in a psychiatric ward].

PMID- 14640001
TI  - [Mechanisms of action of Alzheimer medications].

PMID- 14640003
TI  - [Interstitial nephritis associated with mesalazine therapy].

PMID- 14640004
TI  - [Cardiac attack caused by emotional stress-- the Takotsubo phenomenon].

PMID- 14640005
TI  - [Shoulder pain].

PMID- 14640006
TI  - [Jaundice in a young man].

PMID- 14640007
TI  - New chapter on CKD highlights changes to 15th annual USRDS report.

PMID- 14640008
TI  - Emphasizing patient choice: the modality selection project in ESRD Network 18.
AB  - ESRD Network 18 has identified numerous opportunities from improvement in the
      process of modality selection for incident patients commencing maintenance
      dialysis therapy.  The overall goal for the Network is to ensure that all
      patients are presented with a choice for treatment in a timely manner.  This in
      turn, would lead to better preparation of patients for RRT and hopefully, have a
      positive impact on the morbidity and mortality of maintenance dialysis patients.

PMID- 14640009
TI  - K/DOQI guidelines released on bone metabolism and disease in CKD.

PMID- 14640010
TI  - A decade of clinical practice guideline development. Part 2: Practical
      application.

PMID- 14640011
TI  - The London daily/nocturnal hemodialysis study: a review.

PMID- 14640012
TI  - Physician employment agreements--key considerations.

PMID- 14640014
TI  - Results in KEEP's first report show progress in early identification of CKD
      patients.

PMID- 14640013
TI  - Serum calcium and total calcium load in kidney disease.

PMID- 14640015
TI  - Bridging the differences.

PMID- 14640016
TI  - Dialyzer reuse: the debate continues.

PMID- 14640017
TI  - RenalPro gets a face-lift.

PMID- 14640018
TI  - [Modern geriatric care].

PMID- 14640019
TI  - [Care in the day hospital of the Geriatric Rehabilitation Center of the Bern
      Ziegler Hospital].
AB  - This article summarizes aspects of diagnosis and treatment, resources and
      administrative organization of the geriatric day hospital of the Spital Bern-
      Ziegler.

PMID- 14640020
TI  - [Memory clinic in the day hospital].
AB  - Our Memory Clinic at the Day Hospital has developed from years of existing
      services offered for the outpatient diagnosis of memory disorders. This article
      presents how such two- to three-day outpatient diagnostic programs are held.
      After an initial consultation, the patient is admitted to the day clinic. Then a
      survey of the patient's daily activities is taken, a semi-standardized interview
      is conducted with patients and the caregivers; neuropsychological tests and a
      somatic examination including a functional assessment are carried out. In the
      following, we will discuss how the diagnosis is subsequently rendered on the
      basis of these findings. Frequently asked questions, common problems and
      diagnostic difficulties will be elucidated, while focusing on diagnostic and
      therapeutic discussions and the contents of the consultations.

PMID- 14640021
TI  - [Geriatrics: the day hospital as a part of comprehensive medical care of elderly
      patients--also or especially in threatened rationing].
AB  - The wrong conclusion of elderly people being the reason for increasing costs of
      public health is corrected by several differentiated statements. Geriatrics as a
      comprehensive medicine for the elderly can be realized in an exemplary way, even
      in a day hospital. An attitude of solidarity and a high level of interpersonal
      communication play the important and decisive part.

PMID- 14640022
TI  - [Geriatric care and geriatrics--testing grounds for medical communication].
AB  - The communications between patient and physician is presented as a medical task
      as well as a human encounter and a personal event.

PMID- 14640023
TI  - [Successful aging].
AB  - Age: an annoying burden or a priceless gain? The ancient physicians
      differentiated between senium and senectus to describe old age. In modern-day
      terminology, the former corresponds to the deficit model, the latter to the
      competence model of old age. Its success or failure is dependent on biological,
      psychological, social and mental determinants. In the first part, these four
      determinants will be compared from the perspectives of competence and deficit,
      success and failure. The second part will outline selected meaningful aspects of
      the art of living that are relevant for successful ageing, namely, an awareness
      for the transient nature of life, attention to life, conciliation with oneself,
      F. Nietzsche's higher state of health, attention to god and humor.

PMID- 14640024
TI  - Perspectives. How far is it from E-record vision to reality?

PMID- 14640025
TI  - Challenges of targeting A beta fibrillogenesis and other protein folding
      disorders.

PMID- 14640027
TI  - The amino acid sequence of protein AA from a burro (Equus asinus).
AB  - The primary structure of amyloid fibril protein AA of a burro has been determined
      by Edman degradation. The 80 amino acid residue long protein shows strong
      resemblance to that of other mammalian AA-proteins and differs from equine
      protein AA at 5 positions: Burro/horse positions 20 (Q/N), 44 (R,Q, K/K,Q), 59
      (G,L/G,A), 61 (Q/E) and 65 (N/R).

PMID- 14640026
TI  - Relationship between lobar intracerebral hemorrhage and leukoencephalopathy
      associated with cerebral amyloid angiopathy: clinicopathological study of 64
      Japanese patients.
AB  - Cerebral amyloid angiopathy (CAA) has two major clinical manifestations:
      intracerebral hemorrhages and ischemic lesions. Among these, the lobar type of
      intracerebral hemorrhage (ICH) is a well-known clinical manifestation, while the
      CAA-related diffuse deep white matter degeneration known as leukoencephalopathy
      is thought to be rare. The characteristics of CAA-related leukoencephalopathy are
      still incompletely understood, and the relationship between lobar ICH and
      leukoencephalopathy in patients with CAA has not been properly clarified. The
      main purpose of this study is to elucidate the clinical and histopathological
      features of CAA-related lobar ICH and leukoencephalopathy in order to determine
      whether the degree of deep white matter degeneration parallels the severity of
      CAA-associated vasculopathies that lead to vascular wall rupture. We studied 64
      Japanese patients with histopathologically proven amyloid beta protein (A beta)
      type CAA presenting with lobar ICH (52 biopsy and 12 autopsy). In this study, a
      total of 106 hematomas were observed. CAA-related cerebral hemorrhages tend to
      occur recurrently and multifocally. Multiple simultaneous labor hemorrhages
      occasionally developed (9.4%). CAA-related ICH in the sixth decade was not rare
      (14.1%). Although most patients suffered relapsing and/or multiple severe ICH, no
      patient in our series presented with diffuse leukoencephalopathy. In conclusion,
      A beta type cerebrovascular amyloid deposition causes recurrent, multifocal, and
      often multiple simultaneous ICH even in relatively younger elderly patients, but
      rarely produces diffuse leukoencephalopathy. This suggests that CAA-associated
      vasculopathies that cause vascular wall rupture do not always lead to ischemic
      deep white matter degeneration, and that there may be another unknown
      pathogenetic mechanism producing the latter CAA-related white matter lesion.

PMID- 14640028
TI  - Slower clearance of human SAA1.5 in mice: implications for allele specific
      variation of SAA concentration in human.
AB  - Serum amyloid A (SAA), the serum precursor of the fibrillar component (AA
      proteins) in reactive amyloid deposits, is a multigene product. SAA1, the
      prominent acute phase isotype in serum and also the dominant fibril precursor,
      has several allelic variants. In Japan, each of the three major alleles (1.1, 1.3
      and 1.5) appears with approximately equal frequency. Recent research suggested
      that allele 1.5 has a positive influence on the serum SAA concentration. To
      clarify this, in the present study, recombinant human SAA1.1, SAA1.3 and SAA1.5
      were produced in an E. coli expression system and those species of reconstituted
      high density lipoprotein were injected into mice to examine plasma clearance.
      SAA1.5 disappeared from plasma more slowly than the other two isotypes. This may
      account for the positive influence of allele 1.5 on the serum SAA concentration.

PMID- 14640029
TI  - Heme-oxygenase-1 response, a marker of oxidative stress, in a mouse model of AA
      amyloidosis.
AB  - Expression of heme-oxygenase-1 (HO-1), an important marker of oxidative stress,
      has been studied extensively in the context of Alzheimer's disease. Evidence of
      HO-1 expression during AA amyloidosis is, at best, sketchy. We present
      comparative data on HO-1 response in alveolar hydatid cyst (AHC) infected amyloid
      sensitive (C57BL/6) and amyloid resistant (CE/J) mouse strains. Histochemical and
      peroxidase-immunoperoxidase methods were used to monitor serum amyloid A (SAA)
      and AA fibril deposition and HO-1 expression in hepato-splenic
      reticuloendothelial (RE) cells of the AHC-infected mice prior and during AA
      fibril deposition. Based on the cumulative data, we conclude that HO-1 expression
      corresponded closely with tissue deposition of SAA, but was unrelated to AA
      fibril deposition. To ascertain whether SAA deposition might act as the trigger
      for HO-1 expression in the RE cells, macrophages were incubated for up to 72 h
      with SAA-containing mouse serum. The SAA-treated macrophages, although negative
      for HO-1 protein, demonstrated SAA in the cell extracts and immunocytochemically
      in the vacuolar compartments, indicating macrophage-mediated endocytosis and
      trafficking of SAA. In sum, these results exclude SAA and AA fibrils as the
      primary triggers in the induction of HO-1 expression in RE cells; the potential
      role of inflammatory cytokines in HO-1 response need to be investigated further.

PMID- 14640030
TI  - Tabulation of human transthyretin (TTR) variants, 2003.

PMID- 14640031
TI  - Atypical familial motor neuropathy in patients with mutant TTR Ile68Leu.
AB  - Two sisters from an Italian family shared progressive motor symptoms, preceding
      the onset of sensory and autonomic disturbances. The familial occurrence of
      axonal and slowly progressive polyneuropathy led us to consider these patients as
      candidates for TTR molecular analysis. We found a missense mutation causing
      Ile68Leu TTR substitution in both. The aims of this work are to report the
      possibility of a motor onset of amyloid polyneuropathy and to suggest the search
      for TTR mutations in familial cases of axonal polyneuropathy. Second, to stress
      the possible occurrence of amyloid within the spinal canal as the potential
      pathogenesis and responsible for motor presentation.

PMID- 14640032
TI  - An on-line assay for clinical detection of amyloidogenic transthyretin variants
      directly from serum.
AB  - We report here for the first time the on-line analysis of transthyretin genetic
      variants by mass spectral analysis. The use of mass spectrometry to analyze
      immunoprecipitated transthyretin has been previously described. However, the on
      line analysis of TTR directly from serum reported here will allow for a fully
      automated high throughput analysis. Mutations in the plasma transport protein TTR
      are readily observed and distinguished from normal TTR. Free TTR as well as TTR
      cysteine and TTR-cysteinylglycine adducts are clearly evident. The resulting
      assay from serum to final interpretation requires less than twenty minutes. The
      assay should be an effective first line discriminator of patients who are being
      considered to have Familial Amyloidotic Polyneuropathy (FAP) and an adjunct to
      definitive diagnosis by sequencing of the TTR gene or protein.

PMID- 14640033
TI  - Late-onset familial amyloid polyneuropathy: an autopsy study of two Japanese
      brothers.
AB  - We report an autopsy study of late-onset familial amyloid polyneuropathy with a
      variant transthyretin Val30Met in 2 brothers living in Kyoto, Japan. The disease
      onsets were at 64 and 59 years, and they died at 71 and 74 years old,
      respectively. They exhibited almost the same postmortem findings. Amyloid
      deposition was remarkable in the hearts, but was not seen in the renal glomeruli.
      In the peripheral nervous system, amyloid deposition was most prominent in the
      nerves immediately caudal to ganglia, moderate in the dorsal and sympathetic
      ganglia, and mild in the spinal roots, sciatic nerves, and distal nerves. The
      difference between the amyloid deposition in the proximal portion and distal
      portion of the extremity nerves appeared to be greater in the late-onset type
      than in the ordinary type, and this proximal deposition of amyloid may have
      induced severe distal nerve fiber degeneration.

PMID- 14640034
TI  - The pathogenesis of transthyretin tissue deposition: lessons from transgenic
      mice.
AB  - Attempts to produce animal models of the human transthyretin deposition disorders
      have not been as successful as investigators would wish. While random genomic
      insertion of mutant and wild-type human transthyretin genes has, in some
      instances, produced tissue deposits consisting of the human protein, in no case
      has a model faithfully reproduced the neuropathic pathology seen in FAP patients.
      Examining all the available models it appears that overexpression of the human
      construct is required with a resultant high level of protein production, as
      measured by the serum concentration. Animals, homo- or heterozygous for a single
      copy of a naturally occurring mutant human gene, even a thermodynamically
      unstable allele (leu55pro), do not develop immunohistochemically detectable
      tissue deposits. If the endogenous murine gene is subjected to targeted
      disruption, a small proportion of animals will develop tissue deposits of the
      human protein late in life. The implication of this observation is that the
      murine protein may stabilize mixed tetramers containing both mutant human and
      wild-type murine monomers in a manner similar to that seen in humans with the
      Met119 variant. As in humans with FAP or FAC, parenchymal hepatic deposition of
      either fibrillar or non-fibrillar deposits is uncommon. When TTR concentrations
      are similar in liver and kidney extracts, kidneys show evidence of aggregate
      deposition while livers do not. At least one of the transgenic models shows that
      non-fibrillar deposits precede the appearance of Congophilic tissue deposition, a
      circumstance that has also been seen in early neuropathic lesions of FAP
      patients. While none of the current models is a precise replicant of the human
      disease, the tissue specificity of deposition, the relationship to age in some
      models, the apparent sequential nature of the form of the deposits, and the
      sensitivity to the presence or absence of other gene products all reflect
      properties shared with FAP, FAC and SSA. They thus represent experimental systems
      for exploring factors and generally approachable in intact humans and reasonable
      screening tools for the effectiveness of various therapeutic approaches.

PMID- 14640035
TI  - Familial amyloid polyneuropathy: mechanisms leading to nerve degeneration.
AB  - Familial amyloid polyneuropathy (FAP) manifests itself as a fiber-length
      dependent polyneuropathy predominantly affecting sensory and autonomic nervous
      systems. Endoneurial amyloid deposits can be noxious to nerve fibers in several
      ways including mechanical and toxic effects on nerve fibers, and impairment of
      blood supply. On teased fiber preparations, a mixture of axonal degeneration and
      a lower proportion of segmental demyelination is observed. Within a few years of
      the first symptoms there is a near complete disappearance of myelinated and
      unmyelinated nerve fibers in the nerve samples taken by biopsy. On teased fiber
      preparations, amyloid deposits induce distortion, demyelination and eventually
      distal axonal degeneration of neighboring nerve fibers. This "mechanical" effect
      is associated with a "toxic" effect of amyloid fibrils leading to the
      disappearance of the basal lamina of Schwann cells, followed by death, presumably
      by apoptosis. Amyloid deposits often cluster around endoneurial blood vessels,
      and even invade their wall with subsequent occlusion of endoneurial vessels
      themselves.

PMID- 14640036
TI  - Cellular consequences of transthyretin deposition.
AB  - Mutant forms of transthyretin (TTR) deposit in tissues of patients presenting
      with familial amyloidotic polyneuropathy (FAP). The cellular consequences of
      tissue TTR deposition have only been addressed recently and are summarized here.
      Inflammatory and oxidative stress pathways are triggered by fibrillar and non
      fibrillar TTR deposits, a fact to take into account in future forms of FAP
      treatment.

PMID- 14640037
TI  - Use of genetically altered mice to study the role of serum amyloid P component in
      amyloid deposition.
AB  - A precise role for serum amyloid P component (SAP), a common component of all
      known types of amyloid fibrils, in amyloid deposition in vivo is not known. Thus
      we investigated the relationship between SAP and amyloid deposition, using the
      transgenic mouse model of familial amyloidotic polyneuropathy (FAP). Because high
      serum levels of mouse endogenous or human SAP did not affect human transthyretin
      derived amyloid deporsition in the transgenic mouse model of FAP, we approached
      this question by analyzing the induction of experimental AA amyloidosis in SAP
      deficient and wild-type mice. Our experiments presented compelling evidence that,
      although not essential in the deposition of AA amyloid, SAP significantly
      accelerates the reaction. We then examined the persistence of splenic AA amyloid
      fibrils in SAP-deficient and wild-type mice to assess potential ways of treating
      individuals with amyloidosis. Our results indicated that lack of SAP in AA
      amyloid deposits does not enhance regression of the deposits in vivo and
      suggested that dissociation of bound SAP from AA amyloid deposits would not
      significantly accelerate regression of the deposits in vivo.

PMID- 14640038
TI  - Fibrillogenesis in gelsolin-related familial amyloidosis.
AB  - To clarify the mechanisms involved in amyloid formation in Finnish-type familial
      amyloidosis (FAF), we have tested the in vitro fibrillogenicity of synthetic wild
      type and mutated gelsolin peptide analogs and studied the fragmentation patterns
      of gelsolin in the circulation of FAF patients with the Asn-187 or Tyr-187
      gelsolin mutation. Fibril formation of synthetic peptides having sequence
      homology with wild-type or mutant gelsolins was monitored by Congo-red staining
      and polarization microscopy, negative staining electron microscopy and
      quantitative thioflavine-T fluorometry. Immunoblotting with anti-gelsolin and
      amyloid-specific antibodies and sequence analyses were used to study the
      fragmentation pattern of gelsolin. Ultrastructurally amyloid-like fibrils were
      formed from mutant Asn-187 and Tyr-187 gelsolin peptides. Fluorometric analysis
      revealed highly accelerated fibril formation from the mutant peptides as compared
      with the corresponding wild-type peptides. Addition of mercaptoethanol alone or
      in combination with dithiotreitol tended to enhance fibril formation of the 9-mer
      and 11-mer Asn peptides. Blocking of the C-terminal carboxyl of the mutant Asn
      187 gelsolin182-192 peptide by amidation increased amyloidogenicity. The Tyr-187
      gelsolin mutation, corresponding to the naturally occurring mutation in the
      Danish subtype of FAF, required acidic conditions to form fibrils meeting the
      criteria of amyloid. In FAF patients, in addition to the full-sized gelsolin, a
      series of lower-molecular mass C-terminal fragments of gelsolin (70,000-45,000
      Da) was found in the circulation. In homozygous FAF(Asn-187) the 65-kDa fragment
      containing the amyloid forming region and the 55-kDa fragment, devoid of that
      region, was the major gelsolin species in the plasma. The results indicate that
      the 65-kDa gelsolin fragment derived by alpha-gelsolinase cleavage at the
      mutation-induced novel proteolysis site Arg172-Ala173 represents the putative
      circulating precursor protein of tissue amyloid in FAF and that the Asp187Asn/Tyr
      substitution in gelsolin creates a conformation that is highly fibrillogenic.

PMID- 14640039
TI  - Clinical and therapeutic implications of presymptomatic gene testing for familial
      amyloidotic polyneuropathy (FAP).
AB  - Presymptomatic gene testing for familial amyloidotic polyneuropathies (FAP) is
      integrated in genetic counseling protocols common to other "Later onset,
      hereditary, autosomal dominant, no cure diseases" namely Huntington's Disease
      (HD) and Machado-Joseph disease (MJD). However, presymptomatic gene testing has
      specific clinical and therapeutic implications for FAP. Moreover, at least in
      Portugal, FAP ATTR Val30Met is a serious health problem. The most important
      implications are: the possibility of family planning including prenatal and
      preimplantation diagnosis; treatment with liver transplantation (TX); clinical
      follow-up according to protocols for early diagnosis which will allow patients to
      access therapy in useful time. This concept of useful time in FAP treatment is
      discussed. The growing possibilities of different therapeutic approaches are
      considered. In conclusion, presymptomatic gene testing for FAP may have a
      positive impact on candidate quality and prolongation of life, and on the future
      of disease studies.

PMID- 14640040
TI  - Clinicopathologic and genetic features of early- and late-onset FAP type I (FAP
      ATTR Val30Met) in Japan.
AB  - Type I (transthyretin Val30Met) familial amyloid polyneuropathy (FAP ATTR
      Val30Met) has been reported in relation to two endemic foci in Japan. These cases
      are characterized by a relatively young age at onset, between the second and
      third decade, high penetrance rate, concentration in endemic foci, predominant
      loss of superficial sensation, severe autonomic dysfunction, and atrioventricular
      nodal block requiring pacemaker implantation. In contrast to these endemic cases,
      because of advances in DNA diagnosis, late-onset cases of FAP ATTR Val30Met with
      symptoms appearing at or over 50 years of age are now recognized to occur widely
      throughout Japan. These cases have a male preponderance, low penetrance rate, no
      relationship to endemic foci, sensorimotor symptoms beginning distally in the
      lower extremities with disturbance of both superficial and deep sensation, and
      relatively mild autonomic symptoms. This type of FAP ATTR Val30Met has been
      overlooked because its clinical and genetic features differ from those of
      "typical" early-onset cases. Anticipation of age at onset is known to occur in
      pedigrees from the two endemic foci in Japan, with age at onset becoming younger
      in patients of successive generations. On the other hand, age at onset of
      patients in late-onset families seems to be uniformly late among the patient
      siblings when family history is present. Pathologic findings of the peripheral
      nervous system also differ in accordance with differences of clinical features.
      Loss of dorsal root and sympathetic ganglion neurons was severe in the early
      onset cases, whereas it was only mild to moderate in the late-onset cases.
      Unmyelinated fibers in the biopsied sural nerve specimens of late-onset cases
      seemed to be relatively well preserved compared to those of previously reported
      early-onset cases.

PMID- 14640041
TI  - Clinical and pathological findings of non-Val30Met TTR type familial amyloid
      polyneuropathy in Japan.
AB  - Non-Val30Met TTR type FAP is being increasingly recognized; a total of 21 TTR
      gene mutations related to the development of non-Val30Met type FAP have been
      identified among Japanese. The clinical phenotypes of these FAP kindreds varied
      considerably corresponding to the different mutations of TTR gene. In the nervous
      system, peripheral nerve involvement sometimes started as a carpal tunnel
      syndrome in addition to peripheral somatic and autonomic neuropathy. Brain and
      spinal cord dysfunctions due to leptomeningeal amyloidosis infrequently appeared.
      Severe involvement of the heart was a common finding in the visceral organs,
      which might causally lead to a poor prognosis for the patients with this form of
      FAP. Several patients with ATTR non-Val30Met have recently undergone living
      related partial liver transplantation, and their postoperative courses have been
      under careful investigation.

PMID- 14640042
TI  - Transthyretin-derived senile systemic amyloidosis: clinicopathologic and
      structural considerations.
AB  - Senile systemic amyloidosis (SSA) is a prevalent disease affecting the elderly
      and results from the pathologic deposition, predominantly in the heart, of
      unmutated (wild-type) transthyretin (TTR) molecules. This disorder differs from
      the familial TTR-associated amyloidoses that generally occur in a younger
      population and involves peripheral nerves but, notably, the deposits contain
      mutated (variant) forms of the amyloidogenic precursor protein. To gain further
      insight into the clinicopathologic features and pathogenesis of SSA, we have
      reviewed the post-mortem findings of 33 Swedish individuals (27 men, 6 women) who
      had pronounced cardiac amyloid disease. Additionally, in all cases there were
      amyloid deposits within the lungs. Seven of the patients were uremic, possibly
      due to fibrillar deposits in the renal medullary papilla. In contrast to other
      systemic amyloidoses, none of the 33 had more than minute congophilic material in
      the renal cortex, liver, or spleen. We have also analyzed the chemical
      composition of fibrils extracted from myocardium and have found that the protein
      consisted mainly of C-terminal fragments of TTR starting at positions 46, 49, and
      52. Furthermore, we identified through antigenic mapping, an epitope present on
      the H strand of fibrillar, but not normal, plasma TTR molecules indicating that
      this strand is exposed in fibrils. We suggest that ATTR fibrils may develop both
      from full-length TTR and from C-terminal TTR fragments and that the N-terminal
      part is not necessary for the fibril integrity.

PMID- 14640043
TI  - New therapeutic approaches for familial amyloidotic polyneuropathy (FAP).
AB  - Because the use of liver transplantation as therapy for familial amyloidotic
      polyneuropathy (FAP) has given rise to several problems, an alternative treatment
      is needed. We have tried several other approaches. To suppress production of
      variant transthyretin (TTR) in the liver, we injected purified normal human TTR
      into patients with FAP. Production of variant TTR decreased significantly for 48
      h. However, 1 week after the injection, production returned to levels that were
      almost the same as those before injection. TTR has a rapid turnover, so this
      method cannot be used to suppress production of the harmful protein for an
      extended time. Recent studies suggested that certain metal ions affect
      amyloidogenesis. Among metal ions tested in an in vitro amyloid formation study,
      Cr3+ increased stability of both normal and mutant TTR tetramers and suppressed
      TTR amyloidogenesis induced by low pH. Our findings indicate that Cr3+ acts to
      suppress TTR amyloidogenesis. (Trans, trans)-bromo-2,5-bis-(3-hydroxycarbonyl-4
      hydroxy)styrylbenzene (BSB), a Congo red derivative that binds to amyloid fibrils
      in FAP, as well as to those in senile plaques in Alzheimer's disease, effectively
      suppressed TTR amyloid formation in vitro. BSB may thus be useful for preventing
      amyloid formation. Free radical scavenger therapy was also tried with FAP
      patients but yielded no conclusive results. Finally, an RNA/DNA chimera and
      single-stranded oligonucleotides (SSOs) were tested in vitro and in vivo in an
      attempt to repair the amyloidogenic TTR gene in the liver and retina. On the
      basis of results achieved so far, SSOs are a promising tool for gene therapy.

PMID- 14640044
TI  - Report from the Familial Amyloidotic Polyneuropathy World Transplant Registry
      (FAPWTR) and the Domino Liver Transplant Registry (DLTR).
AB  - Familial amyloidotic polyneuropathy (FAP) is a fatal disease, belonging to a
      group of systemic disorders caused by an amyloidogenic transthyretin (TTR)
      variant. Orthotopic liver transplantation (OLT) eliminates the source of the
      variant TTR molecule, and is presently the only known curative treatment. A
      fascinating consequence of this treatment is the possibility of retransplanting
      the removed FAP liver into another non-FAP patient, which created the so-called
      domino liver transplantation (DLT) procedure. The Familial Amyloidotic
      Polyneuropathy World Transplant Registry (FAPWTR) was initiated in 1995, and in
      1999 a Domino Liver Transplantation Registry (DLTR) was created. Herein data from
      these Registries are presented. A total number of 56 centers in 16 countries have
      performed OLT for FAP, and, today, approximately 65-70 OLTs are performed
      annually worldwide. During the last decade, a total of 623 patients have
      undergone 660 OLTs. Patient survival is excellent and comparable to the survival
      with OLT performed for other chronic liver disorders. Twenty-six centers in 12
      countries have reported recipients of DLT grafts and presently 30-35 DLTs are
      performed annually. The FAPWTR and DLTR have become useful tools in evaluating
      the potential risks and benefits of these relatively new therapeutic options, in
      addition to encouraging a rewarding collaboration between centers involved in the
      management of these patients.

PMID- 14640045
TI  - Impact of liver transplantation on familial amyloidotic polyneuropathy (FAP)
      patients' symptoms and complications.
AB  - Liver transplantation for transthyretin (TTR) amyloidosis is today an accepted
      treatment for the disease. However, the long-term outcome of the procedure
      remains to be elucidated, especially for non-Val30Met TTR mutations. Using serum
      amyloid P (SAP) component scintigraphy, amyloid deposits have been shown to
      decrease in approximately 50% of the patients, but this finding has not been
      confirmed in biopsy specimens. However, free radical activity has been reduced
      after transplantation. Conflicting results regarding neurological disturbances
      have emerged, but some improvement may take place, especially in patients
      transplanted at an early stage of the disease. For heart complications, recent
      reports indicate that increased cardiomyopathy after transplantation is a common
      finding, and that the development of arrhythmia is also common. Even though an
      improvement of the patients' nutritional status is observed after
      transplantation, gastrointestinal disturbances appear to be unchanged after the
      procedure. Kidney function deteriorates initially after transplantation, but
      thereafter it remains stable. Since TTR is produced locally in the eye,
      development of amyloid deposits in the eye has been reported in several cases
      after transplantation. Transplantation for FAP should be performed early on after
      onset of the disease, since the majority of symptoms will remain unchanged after
      the procedure. The patients should be followed closely after transplantation to
      detect the development of heart arrhythmia.

PMID- 14640046
TI  - Domino liver transplantation using FAP grafts. HUC experience--hopes and
      realities.
AB  - Domino liver transplantation using FAP livers (DLTx/FAP) has become a worldwide
      strategy that is contributing significantly to the increase in liver grafts
      offered in Portugal. The safety of the procedure both in the FAP donors and in
      the recipients is emphasized in the series of 64 DLTx/FAP that has already been
      performed in the Hospital of the University of Coimbra (HUC). The occurrence of
      amyloidosis in the long-term survivors after DLTx/FAP is a serious possibility,
      although after 6 and 7 years post-transplant no symptoms have been reported by
      any of the patients. Indeed, amyloid deposits, although small, have been found in
      the skin and nerve biopsies of the first domino recipients (HUC unpublished
      data). Hopes that the disease will have a slow course in non-genetically affected
      patients still awaits the proof of time. Thus, DLTx/FAP should be considered an
      experimental procedure, although there is good reason to expect that the
      amyloidosis in the DLTx/FAP recipients will have a longer time course than in the
      genetically affected donors. The ethical implications of all these facts and
      expectations are discussed. A case by case approach is recommended. In such an
      approach, individual prognosis, urgency, graft shortage and the will of very well
      informed patients or their legal representatives are determinants for judicious
      decisions when considering DLTx/FAP in patients under 50 years of age.

PMID- 14640047
TI  - Renal disease: FAQs from GPs.

PMID- 14640048
TI  - Managing renal stone disease.

PMID- 14640049
TI  - Casebook: proteinuria.

PMID- 14640050
TI  - Drug effects on the kidney.

PMID- 14640051
TI  - The patient with renal cell cancer.

PMID- 14640052
TI  - Key questions in benign prostatic hyperplasia.

PMID- 14640054
TI  - [A white lesion of the oral mucosa: leukoplakia?].
AB  - In three patients, two men aged 50 and 44 years and a woman aged 56 years, an
      apparently identical white lesion of the oral mucosa was found. The first patient
      appeared to have an irritation due to vigorous toothbrushing, which disappeared
      after reducing the brushing frequency and using a soft brush, the second patient
      had a lichen planus, for which a wait and see policy was adopted, and the third
      patient had verrucous hyperplasia with dysplasia which was treated by CO2-laser
      evaporation. Oral leukoplakia occurs frequently together with other white
      lesions. Leukoplakia is a diagnosis by exclusion and the term should be used as a
      clinical diagnosis only. When a biopsy is taken, the term leukoplakia is replaced
      by the diagnosis obtained histologically. About 5% of leukoplakias progress to
      cancer in a mean observation period of 5 years. Sufficient knowledge of the
      nomenclature and clinical characteristics of oral white lesions may contribute to
      the prevention of malignancies and unnecessary referral to a medical specialist.

PMID- 14640055
TI  - [Cholinergic deficiency syndrome as an indicator for the cholinesterase
      inhibitors].
AB  - Cholinesterase inhibitors are licensed for the treatment of dementia in
      Alzheimer's disease. In clinical practice, these drugs have little effect on the
      cognitive symptoms of dementia. Several studies report a beneficial effect of
      cholinesterase inhibitors on neuropsychiatric symptoms. We hypothesise that
      symptoms such as the impairment of attention and concentration, anxiety,
      restlessness and hallucinations, delineate a specific central cholinergic
      deficiency syndrome. It is postulated that this syndrome crosses boundaries of
      nosological entities and occurs in various neurodegenerative diseases. Symptoms
      resulting from cholinergic deficiency might be a much better target for treatment
      than cognitive deficits.

PMID- 14640056
TI  - [Prevention of colorectal cancer: acetylsalicyclic acid and cyclo-oxygenase-2
      inhibitors are only partially effective].
AB  - Acetylsalicylic acid was recently shown to inhibit the development of colorectal
      adenomas in subjects with a moderately increased risk for colorectal cancer. The
      mechanisms by which acetylsalicylic acid and other NSAIDs, including COX-2
      inhibitors, exert this effect include: inhibition of COX-2, induction of
      apoptosis and induction of the P21 protein that controls the development of crypt
      cells. For the majority of the population, a healthy lifestyle and healthy eating
      habits are the best means of preventing colorectal cancer. In addition,
      population-wide screening should be encouraged. For people with an increased risk
      of colorectal cancer, acetylsalicylic acid only has a partial effect and
      therefore endoscopic surveillance is still indicated. Sulindac or celecoxib may
      be useful for patients with familial adenomatous polyposis and in particular for
      inhibiting the development of rectal adenomas after subtotal colectomy with
      ileorectal anastomosis. However, in these cases endoscopic surveillance is also
      still necessary.

PMID- 14640057
TI  - [Cyclooxygenase(COX)-2-inhibition in the prevention and treatment of colorectal
      carcinoma].
AB  - Epidemiological studies have found that long-term use of non-steroidal anti
      inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal cancer
      (CRC). Cyclooxygenase (COX)-2 expression is present in colorectal cancer and
      overexpression is associated with metastases and poorer prognosis in multivariate
      analysis. NSAID treatment results in a reduction of the incidence of colorectal
      adenoma in patients with familial adenomatous polyposis, in patients with a
      history of colorectal adenomas and in patients with a history of CRC. Pre
      clinical research shows that COX-2 expression is associated with cell
      proliferation, angiogenesis, apoptosis inhibition and local immune-down
      modulation. An anticarcinogenic effect has been shown specifically in selective
      COX-2 inhibitors in animal models. Selective COX-2 inhibitors have fewer adverse
      effects than the non-selective NSAIDs and are promising chemopreventative and
      chemotherapeutical agents. The effects of selective COX-2 inhibition in the
      prevention of and treatment for colorectal carcinoma will be investigated in
      clinical randomized multicentre trials.

PMID- 14640058
TI  - [Beta 2 agonists in infants and young children with a wheeze: often ineffective].
AB  - Wheezing is a common symptom in infants and young children, for which the
      treatment of choice is beta 2-agonists. However, the efficacy of beta 2-agonists
      in children aged 2 years and younger is not evidence based. Approximately 60% of
      wheezy infants do not have asthma, but a transient condition related to airway
      obstruction that is associated with coughing, wheezing and/or stuffiness: so
      called infant asthma. In infants, beta 2-agonists may make the airways more
      compliant, resulting in more severe airway obstruction. In addition to this, beta
      2-agonists increase the metabolism and cause ventilation-perfusion mismatch in
      the lung which may lead to a decrease in the oxygen saturation. Since it is
      unclear which infants will benefit from beta 2-agonists, a trial treatment is
      justified and this should be critically evaluated. Beneficial clinical effects of
      beta 2-agonists are a reduction in breathing frequency, reduction in or
      disappearance of retractions or the use of accessory respiratory muscles during
      breathing and possibly an increase in oxygen saturation. beta 2-agonists are
      effective and safe for the treatment of asthma. However, there is no basis for
      continuing the treatment in the case of infants and young children with an airway
      obstruction unless there is a clinically favourable effect.

PMID- 14640059
TI  - [European standard regarding clothing and protection against ultraviolet
      radiation].
AB  - Overexposure to ultraviolet radiation (UVR) causes skin damage. An increasing
      awareness of this must result in people consciously wanting to protect themselves
      from UVR by means of clothing. The first part of the European standard on UVR
      protective clothing--about test methods--is now available. In the second part the
      classification and labelling of UVR-protective clothing are detailed. The degree
      of protection the clothing provides against UVR is expressed as the ultraviolet
      protection factor (UPF). The UPF is inversely proportional to the quantity of UVR
      which the clothing allows through. UVR-protective clothing which satisfies the
      European standard will bear the European UPF label '40+'. To obtain this label
      the entire clothing must have a UPF of at least 40. The wording: 'Sun exposure
      causes skin damage', 'Only covered areas are protected' and 'The protection
      offered by this item may be reduced with use or if the material is stretched or
      wet' must be added to the label.

PMID- 14640060
TI  - [Diagnostic image (164). A man who drank formalin by mistake. Caustic lesions of
      esophagus and stomach].
AB  - A 71-year-old male was admitted because of unintentional ingestion of formalin,
      which caused severe caustic lesions of oesophagus and stomach.

PMID- 14640061
TI  - [Increased number of systematic reviews in the Netherlands in the period 1991
      2000].
AB  - OBJECTIVE: To survey systematic reviews (SRs) as publication type in the
      Netherlands, with emphasis on differences between Cochrane reviews and SRs in
      printed journals. DESIGN: Bibliometric study. METHOD: A systematic search was
      carried out in Medline, EMBASE and the Cochrane Library for published systematic
      reviews of Dutch origin in the period 1991-2000. For each SR, the year of
      publication, the number of original articles included, the subject matter and the
      impact factor of the journal were identified. RESULTS: A total of 289 SRs were
      retrieved, of which 12% were Cochrane reviews. The number of SRs increased
      exponentially during this decade. The majority (56%) of the SRs concerned a
      therapeutic intervention. SRs were published in journals with a moderate to good
      impact factor (median impact factor 2.59). On average, compared to SRs published
      in the Cochrane Library, the SRs published in the general medical literature
      included significantly more original articles (28.8 versus 13.7; p < 0.05). This
      may be caused by the fact that the clinical questions for Cochrane reviews are
      more focused as compared with non-Cochrane SRs or by the fact that Cochrane
      review groups may have more stringent quality requirements for inclusion of an
      article in a review. CONCLUSIONS: The SR as a publication type showed a rapid
      growth in one decade and was published in important medical journals. Cochrane
      reviews represented a substantial proportion of the overall number of SRs in the
      Netherlands.

PMID- 14640062
TI  - [Five patients with metastasized basal-cell carcinoma].
AB  - During the period 1986-2001, a metastasised basal-cell carcinoma of the head was
      diagnosed in five patients (a 35-year-old woman and four men aged 40, 44, 54 and
      54 years) at the Utrecht University Medical Centre, the Netherlands. Metastases
      were found in the cervical lymph nodes, the skeleton, the parotid region and the
      lungs. The tumours were all of the morphoeic or 'wispy' type. The treatment
      consisted of excision and sometimes radiotherapy. Two patients died, one of whom
      of a cause unrelated to the tumour, two patients were free of symptoms 24 months
      after the last treatment and one patient was still being treated with
      radiotherapy. It is often assumed that basal-cell carcinomas do not metastasised,
      but a frequency of 0.0028-0.55% is reported in the literature. An important risk
      factor is the size of the tumour. Surgical excision or Mohs' micrographic surgery
      is the preferred method of treatment because this allows histological inspection
      of the excised margins. Due to the low incidence, there are no clear therapeutic
      guidelines for the treatment of patients with metastasised basal-cell carcinoma.

PMID- 14640063
TI  - [From the library of the Netherlands Journal of Medicine. Rudolf Virchow: Die
      Cellularpathologie in ihrer Begrundung auf physiologische und pathologische
      Gewebelehre; 1858].
AB  - With the publication of Die Cellularpathologie in ihrer Begrundung auf
      physiologische und pathologische Gewebelehre in 1858, the author Rudolf Virchow
      (1821-1902) originated the idea that each cell in each living organism, both
      plant and animal, originates from another cell and that the origin of disease can
      only be located in the cell. The book laid the foundations for cell pathology as
      a scientific discipline and was the most important publication by Virchow, who as
      doctor and statesman gathered so much fame that he became almost a mythical
      figure in his own time. The finding that every cell originates from another cell
      and does not develop from amorphous interstitium is actually attributable to
      Robert Remak.

PMID- 14640064
TI  - [Rapidly destructive hip disease with resultant iliopectineal bursitis].

PMID- 14640065
TI  - ['Tired of life': a reason to evaluate physical handicaps].

PMID- 14640066
TI  - [Irreversible coma following hypoglycemia in Sheehan syndrome with adrenocortical
      insufficiency].

PMID- 14640067
TI  - [Time for professionalising the system of medical ethics review in the
      Netherlands].

PMID- 14640068
TI  - Payment policy and inefficient benefits in the Medicare+Choice program.
AB  - We investigated whether constraints on premium rebates by health plans in the
      Medicare+Choice program result in inefficient benefits. Since relationships
      between revenue and benefits could be confounded by unobserved variation in the
      cost of coverage, we took advantage of natural experiment that occurred following
      passage of the Benefits Improvement and Protection Act of 2000. Our findings
      indicate that benefits in zero premium plans were more sensitive to changes in
      payment rates than were benefits in plans that charged nonzero premiums. These
      results strongly suggest that current Medicare policy induces plans to offer
      benefits that are not valued by enrollees at or above their cost.

PMID- 14640069
TI  - Observations on the development of Echinococcus multilocularis in cats.
AB  - The development of a European isolate of Echinococcus multilocularis was compared
      in cats and dogs at the end of the prepatent period. Echinococcus multilocularis
      established in all dogs and cats, but worm recovery was significantly greater
      from dogs than from cats. Overall, worms in cats were not as advanced as those in
      dogs in terms of development and maturation, but there was no evidence of
      retarded development or stunted forms. These results confirm that dogs are highly
      susceptible to E. multilocularis, whereas cats have lower and more variable
      recovery rates. However, because cats produce thick-shelled eggs of E.
      multilocularis after experimental and natural infections, they have to be
      regarded as potential sources of infection both for intermediate and accidental
      hosts, including humans. However, their general role in the epidemiology of the
      infection has yet to be determined.

PMID- 14640071
TI  - Clinical pastoral education and the value of empirical research: examples from
      Australian and New Zealand datum.
AB  - This article argues in favor of clinical pastoral education programs
      incorporating research methods as part of a standard neo-curriculum for the 21st
      Century. It suggests that the benefits of such a curriculum would be useful in
      scientifically validating and evaluating pastoral care practice at a 'micro,'
      'meso' and 'macro' level. This argument is supported with the presentation of
      Australian and New Zealand descriptive statistical datum exploring the
      involvement of chaplains in patient bioethical decisions, staff bioethical
      decision-making and the involvement of chaplains on hospital institutional
      research ethics committees.

PMID- 14640070
TI  - Identification of the high-virulence clone of group B streptococci by using a
      probe containing a putative aldolase gene.
AB  - A high-virulence clone (HVC) was proposed as causing much of the morbidity and
      mortality when a collection of group B Streptococcus (GBS) isolates was examined
      by multi-locus enzyme electrophoresis. HVC isolates could be further
      distinguished by their inability to grow at 40 degrees C, and a temperature
      sensitive aldolase was identified as responsible for this characteristic. In the
      present study, the HVC was sought in a collection of 57 GBS isolates by
      hybridization with a probe containing a putative aldolase gene on genomic DNA
      restriction enzyme digests. Isolates were initially classified as HVC or non-HVC
      by their inability to grow at 40 degrees C. Three serotype III invasive isolates
      had the HVC control restriction/hybridization pattern. They were also unable to
      grow at 40 degrees C. The remaining 11 invasive and all carrier isolates showed a
      pattern identical to that of the non-HVC control. These results provide
      additional support for the existence of a highly virulent clonal group among
      serotype III isolates and suggest that hybridization with a probe containing the
      aldolase gene on DNA restriction enzyme digests can be an alternative method for
      identifying highly virulent isolates.

PMID- 14640072
TI  - Pulmonary venoconstriction and the pharmacology of respiratory distress.

PMID- 14640073
TI  - Pulmonary vasoconstriction and the pharmacology of respiratory distress
      (continued).

PMID- 14640074
TI  - Cloning and characterization of a novel Hsp100/Clp gene (osClpD) from Oryza
      sativa.
AB  - A novel osClpD gene, encoding a highly conservative ClpD subfamily member, was
      first isolated and characterized from Oryza sativa. The full-length cDNA of
      osClpD gene was 3140 bp and contained a 2884 bp open reading frame encoding a 938
      amino acid protein. The phylogenetic tree and blast search showed that OSClpD
      belonged to the ClpD subfamily of the Hsp100/Clp family, and contained all
      protein motifs characteristic for the ClpD subfamily of Hsp100/Clp proteins. The
      real-time quantitative PCR analysis proved that it was inducible by water deficit
      and temperature stress in vegetative tissues.

PMID- 14640075
TI  - Cloning and characterization of a curcin gene encoding a ribosome inactivating
      protein from Jatropha curcas.
AB  - A curcin gene was isolated by using genomic walker technology and revealed to
      encode the type-1 ribosome inactivating proteins (RIPs). Analysis of 1802 bp
      segments revealed the gene including a 694 bp 5' flanking region, a 882 bp open
      read frame (ORF) and a 226 bp 3' flanking region. There are one putative TATA
      boxes and two possible CAAT box lie in the 5'-flanking region. The ORF encodes a
      32 kDa precursor, which contains a 42 amino acid signal peptide. Two possible
      polyadenylation signals are found in the 3'-flanking region. No introns were
      found, which is typical of other RIPs gene that has been sequenced. The deduced
      amino acid sequence of Curcin gene coding region shares high homology with RIPs,
      e.g. ricin A-chain, gelonin, abrin A-chain, bryodin, trichosanthin and
      momorcharin, which were found to be 34% (99/287), 34% (98/287), 37% (89/240), 34%
      (86/249), 36% (87/241) and 36% (88/241), respectively. The cloning of the gene is
      important foundation to further study the structure, expression and regulation
      mechanism.

PMID- 14640076
TI  - [Chronic subthalamus stimulation for the treatment of Parkinson's disease.
      Analysis of results by classes of symptoms and adverse effects].

PMID- 14640077
TI  - Internal dosimetry of radionuclides. Occupational, public and medical exposure.
      Proceedings of a workshop at New College, Oxford. Oxford, United Kingdom.
      September 9-12, 2002.

PMID- 14640078
TI  - Candidature for and delivery of audiological services: special needs of older
      people. Proceeding of the Eriksholm Workshop. Eriksholm, Denmark. November 2001.

PMID- 14640079
TI  - Assessment of auditory communication: from lab to real life. Proceedings of a
      workshop. Orebro, Sweden. September 6-8, 2001.

PMID- 14640080
TI  - Proceedings of the 10th International Congress on Antiphospholipid Antibodies.
      Sicily, Italy, September 29-October 3, 2002.

PMID- 14640081
TI  - Focus on parasitology. Selected papers from the 19th International Conference of
      the World Association for the Advancement of Veterinary Parasitology (WAAVP). New
      Orleans, Louisiana, USA. August 10-14, 2003.

PMID- 14640082
TI  - Special issue in honour of John T. Edsall.

PMID- 14640083
TI  - Proceedings of the Fourth Working Conference of the International Medical
      Informatics Association Working Group on Health Information Systems. April 2002.
      Heidelberg, Germany.

PMID- 14640084
TI  - Update on atrial fibrillation: the Coburg Symposium. Coburg, Germany. April 13,
      2002.

PMID- 14640085
TI  - Innovative strategies in managing shiftwork. Proceedings of the 15th
      International Symposium on Night and Shiftwork. Hayama, Japan. September 10-13,
      2001.

PMID- 14640086
TI  - [Medical chronobiology. Proceedings of the Auxois conference, January 2002].

PMID- 14640087
TI  - Proceedings of the Leukodystrophies Symposium of the Child Neurology Society
      Annual Meeting. Washington, DC, USA. October 9, 2002.

PMID- 14640088
TI  - Automated quantification of mitral valve regurgitation based on normalized
      centerline velocity distribution.
AB  - Previous echocardiographic techniques for quantifying valvular regurgitation are
      limited by factors including uncertainties for orifice location and a hemispheric
      convergence assumption that often results in over- and underestimation of flow
      rate and regurgitant orifice area. Using computational fluid dynamics
      simulations, these factors were eliminated, allowing a more accurate assessment
      of regurgitation. A model was developed to allow automated quantification of
      regurgitant orifice diameter based on the centerline velocity data available from
      color M-mode echocardiography. The model, validated using in vitro unsteady flow
      data, demonstrated improved accuracy for orifice diameter (y=0.95x + 0.38,
      r=0.96) and volume (y=1.18x - 4.72, r=0.93).

PMID- 14640089
TI  - Do nonlinearities play a significant role in short term, beat-to-beat
      variability?
AB  - Numerous studies of short-term beat-to-beat variability in cardiovascular signals
      have not resolved the debate about the completeness of linear analysis
      techniques. This aim of this paper is to evaluate further the role of
      nonlinearities in short-term, beat-to-beat variability. We compared linear
      autoregressive moving average (ARMA) and nonlinear neural network (NN) models for
      predicting instantaneous heart rate (HR) and mean arterial blood pressure (BP)
      from past HR and BP. To evaluate these models, we used HR and BP time series from
      the MIMIC database. Experimental results indicate that NN-based nonlinearities do
      not play a significant role and suggest that ARMA linear analysis techniques
      provide adequate characterization of the system dynamics responsible for
      generating short-term, beat-to-beat variability.

PMID- 14640091
TI  - [Abstracts of the 76th annual meeting of the Japan Society for Occupational
      Health. Yamaguchi, Japan. April 23-26, 2003].

PMID- 14640090
TI  - Introduction of computational models to PhysioNet.
AB  - PhysioNet is a national research resource that provides experimental data sets
      and open-source software for their analysis. Computational modeling can
      complement studies of these experimental data sets so as to facilitate the
      advancement of physiologic research. Thus, in order to introduce computational
      models to PhysioNet, we have developed and posted a cardiovascular model designed
      for research that generates reasonable human pulsatile hemodynamic waveforms,
      cardiac output and venous return curves, and beat-to-beat variability. Some of
      the key features of the software include: 1) compatibility with PhysioNet's open
      source data analysis software; 2) online viewing and parameter updating as the
      data are being calculated; 3) off-line viewing after completion of the
      simulation; 4) pre-compiled Linux binaries; 5) open-source code that may be
      compiled on other platforms; and 6) an extensive user's manual and software
      guide.

PMID- 14640092
TI  - Efficient hemodynamic event detection utilizing relational databases and wavelet
      analysis.
AB  - Development of a temporal query framework for time-oriented medical databases has
      hitherto been a challenging problem. We describe a novel method for the detection
      of hemodynamic events in multiparameter trends utilizing wavelet coefficients in
      a MySQL relational database. Storage of the wavelet coefficients allowed for a
      compact representation of the trends, and provided robust descriptors for the
      dynamics of the parameter time series. A data model was developed to allow for
      simplified queries along several dimensions and time scales. Of particular
      importance, the data model and wavelet framework allowed for queries to be
      processed with minimal table-join operations. A web-based search engine was
      developed to allow for user-defined queries. Typical queries required between
      0.01 and 0.02 seconds, with at least two orders of magnitude improvement in speed
      over conventional queries. This powerful and innovative structure will facilitate
      research on large-scale time-oriented medical databases.

PMID- 14640093
TI  - Model-based parameter estimation using cardiovascular response to orthostatic
      stress.
AB  - This paper presents a cardiovascular model that is capable of simulating the
      short-term (< or approximately equal to 3 min) transient hemodynamic response to
      gravitational stress and a gradient-based optimization method that allows for the
      automated estimation of model parameters from simulated or experimental data. We
      perform a sensitivity analysis of the transient heart rate response to determine
      which parameters of the model impact the heart rate dynamics significantly. We
      subsequently include only those parameters in the estimation routine that impact
      the transient heart rate dynamics substantially. We apply the estimation
      algorithm to both simulated and real data and showed that restriction to the 20
      most important parameters does not impair our ability to match the data.

PMID- 14640094
TI  - Effects of depressed myocardial contractility induced by microgravity on
      cardiovascular response to orthostatic stress: a computer simulation.
AB  - The aim of present study is to investigate the role played by the depression of
      myocardial contractility in the mechanism of cardiovascular deconditioning and
      orthostatic intolerance (OI) induced by space weightlessness. Based on our
      previous model, which was used to simulate cardiovascular response to lower body
      negative pressure (LBNP), we incorporated the factor of changes of myocardial
      contractility into the model by multiplying a coefficient to the time-varying
      elastance that represents the changes of cardiac contractility. By decreasing the
      coefficient progressively, we simulated the changes of heart rate (HR), blood
      pressure (BP), and cardiac output (CO) during LBNP after 0-30% of myocardial
      contractility depression combined with 12% decrease of the total blood volume.
      Simulation results indicate that depressed myocardial contractility induces more
      augment of HR, and more decrement of BP and CO during LBNP and suggest that the
      depression of myocardial contractility degenerate cardiovascular response to
      orthostatic stress.

PMID- 14640095
TI  - Compression of echocardiographic scan line data using wavelet packet transform.
AB  - An efficient compression strategy is indispensable for digital echocardiography.
      Previous work has suggested improved results utilizing wavelet transforms in the
      compression of 2D echocardiographic images. Set partitioning in hierarchical
      trees (SPIHT) was modified to compress echocardiographic scanline data based on
      the wavelet packet transform. A compression ratio of at least 94:1 resulted in
      preserved image quality.

PMID- 14640096
TI  - Clinical quiz. Malakoplakia of rectum and anal canal in childhood.

PMID- 14640098
TI  - Adjuvant medical therapies after portoenterostomy for biliary atresia: time for
      randomized controlled trial.

PMID- 14640097
TI  - Evidence of correlated functional magnetic resonance imaging signals between
      distant human brains.

PMID- 14640099
TI  - Pouchitis prevention with probiotics.

PMID- 14640100
TI  - Improvement of hypertension prevention and management using evidence-based
      medicine.

PMID- 14640101
TI  - Measures to intensifying the prevention and treatment of AIDS in China.

PMID- 14640102
TI  - Development of oral and maxillofacial oncology in China.

PMID- 14640103
TI  - Automated assessment of noninvasive filling pressure using color Doppler M-mode
      echocardiography.
AB  - Assessment of left ventricular filling pressure usually requires invasive
      hemodynamic monitoring to follow the progression of disease or the response to
      therapy. Previous investigations have shown accurate estimation of wedge pressure
      using noninvasive Doppler information obtained from the ratio of the wave
      propagation slope from color M-mode (CMM) images and the peak early diastolic
      filling velocity from transmitral Doppler images. This study reports an automated
      algorithm that derives an estimate of wedge pressure based on the spatiotemporal
      velocity distribution available from digital CMM Doppler images of LV filling.

PMID- 14640104
TI  - Mental health in China: current status and prevention and control of mental
      disorders.

PMID- 14640105
TI  - Myasthenia gravis in pediatric and elderly patients.
AB  - OBJECTIVE: To determine whether the clinical and pathologic characteristics and
      prognoses of myasthenia gravis (MG) patients below 15 years differ from those
      patients over 50 years after thymectomy. METHODS: We reviewed the registry
      material of 30 pediatric and 32 elderly MG patients after thymectomy, including
      their age, sex, clinical classification, pathological types, and prognoses. The
      Chi-square test or Wilcoxon's rank-sum test was used to determine the statistical
      differences between the children and elderly groups. RESULTS: No significant
      difference was seen in sex distribution between the two groups. (Chi-square test,
      P=0.625), but there were differences in clinical classification: more type I was
      observed in the pediatric group than in the elderly group, but more type II or
      III was seen in the elderly group (Wilcoxon's rank-sum test, P<0.001). As to
      pathological types, the pediatric group was also significantly different from the
      elderly group (Chi-square test, P<0.01). All of the patients (100%) in the
      pediatric group had thymus hyperplasia, but in the elderly group more than half
      (56.26%) were found to have thymoma (benign or malignant). The prognoses after
      thymectomy were better in the pediatric group than in the elderly group
      (Wilcoxon's rank-sum test, P<0.001). CONCLUSIONS: Because the prognoses are
      generally better than those of the elderly patients, we should be careful when
      operating on pediatric patients of ocular type. The elderly patients tend to
      receive more aggressive treatment because of more severe generalized types often
      associated with thymoma and poor prognoses. Both pediatric and elderly patients
      are seldom associated with other autoimmune disease.

PMID- 14640106
TI  - Retroviral endostatin gene transfer inhibits human colon cancer cell growth in
      vivo.
AB  - OBJECTIVE: To investigate the therapeutic effect of retroviral endostatin gene
      transfer on the human colon cancer cell line, LoVo. METHODS: A retroviral vector
      pLESSN expressing secretable endostatin was constructed and packaged with a titer
      of 8.2 x 10(5) CFU/ml. A LoVo cell line was subjected to retrovirus-mediated
      endostatin gene transfer. The proviral integration of endostatin was analyzed
      with PCR. The function of endostatin was tested by MTT assay in vitro and a mouse
      xenograft model in vivo. RESULTS: After transfection and superinfection,
      amphotropic retrovirus was collected, and transduction with amphotropic
      retroviruses resulted in endostatin proviral integration. The endostatin secreted
      by transduced LoVo cells markedly inhibited cell growth up to 67% (P<0.001),
      compared with the control cells. The gene expression of endostatin in LoVo colon
      tumor cells significantly inhibited tumor growth in vivo. There was an 86%
      reduction in tumor size in the endostatin-transduced group, accompanied by a
      reduction in vessels, compared with the control group (P<0.01). CONCLUSION:
      Retroviruses can allow functional expression of the endostatin gene in human
      colon tumors, showing promise for an antitumor strategy using antiangiogenesis.

PMID- 14640107
TI  - Unique GGT --> GTT mutation at K-ras codon 12 in six human pancreatic cancer cell
      lines from Chinese patients.
AB  - OBJECTIVE: To investigate the K-ras mutation pattern in six pancreatic cancer
      cell lines from Chinese patients. METHODS: All six cell lines were analyzed for
      mutation in exon 1 of the K-ras gene by polymerase chain reaction (PCR) and
      direct sequencing. RESULTS: All 6 pancreatic cancer cell lines had GGT --> GTT
      mutation at K-ras codon 12 but no mutations at codon 13. CONCLUSION: The unique
      GGT --> GTT mutation at codon 12 plays a potential role in the carcinogenesis of
      pancreatic cancers in Chinese.

PMID- 14640108
TI  - Successful resection of enterovesical fistula in a patient with sigmoid colonic
      malignancy.

PMID- 14640109
TI  - Noninvasive assessment of mitral inertness [correction of inertance]: clinical
      results with numerical model validation.
AB  - Inertial forces (Mdv/dt) are a significant component of transmitral flow, but
      cannot be measured with Doppler echo. We validated a method of estimating Mdv/dt.
      Ten patients had a dual sensor transmitral (TM) catheter placed during cardiac
      surgery. Doppler and 2D echo was performed while acquiring LA and LV pressures.
      Mdv/dt was determined from the Bernoulli equation using Doppler velocities and TM
      gradients. Results were compared with numerical modeling. TM gradients (range:
      1.04-14.24 mmHg) consisted of 74.0 +/- 11.0% inertial forcers (range: 0.6-12.9
      mmHg). Multivariate analysis predicted Mdv/dt = -4.171(S/D (RATIO)) +
      0.063(LAvolume-max) + 5. Using this equation, a strong relationship was obtained
      for the clinical dataset (y=0.98x - 0.045, r=0.90) and the results of numerical
      modeling (y=0.96x - 0.16, r=0.84). TM gradients are mainly inertial and, as
      validated by modeling, can be estimated with echocardiography.

PMID- 14640110
TI  - Relationship between systolic and diastolic function with improvements in forward
      stroke volume following reduction in mitral regurgitation.
AB  - Efforts to improve mitral regurgitation (MR) are often performed in conjunction
      with coronary revascularization. However, the independent effects of a reduced MR
      area (MRa) are difficult to quantify. Using a previously developed cardiovascular
      model, ventricular contractility (elastance 1-8 mmHg/ml) and relaxation (tau: 40
      150 msec) were independently adjusted for four grades of MR orifice areas (0.0 to
      0.8 cm2). Improvements in forward stroke volume (fSV) were determined for the
      permutations of reduced MRa. For all conditions, LV end-diastolic pressure and
      volumes ranged from 7.3-24.2 mmHg and 64.8-174.3 ml, respectively. Overall, fSV
      ranged from 36.0-89.4 (mean: 64.2 +/- 12.8) ml, improved between 6.4 and 35.3%
      (mean: 15.6 +/- 8.1%), and was best predicted by (r=0.97, p<0.01)
      %delta(fSV)[correction of fVS]=34[MRa initial] - 46[MRa final] -0.5[elastance].
      Reduced MRa, independent of relaxation and minimally influence by contractility,
      yield improved fSVs.

PMID- 14640111
TI  - Chondroblastoma of temporomandibular region: report of 3 cases.

PMID- 14640112
TI  - Bullous oral lichen planus: report of two cases.

PMID- 14640113
TI  - Gene symbol: IRF6. Disease: Van der Woude syndrome.

PMID- 14640114
TI  - Gene symbol: CYP1B1. Disease: glaucoma, primary congenital.

PMID- 14640116
TI  - Gene symbol: MY0C (GLC1A). Disease: glaucoma 1, open angle.

PMID- 14640117
TI  - Gene symbol: IRF6. Disease: Van der Woude syndrome.

PMID- 14640118
TI  - Total arterial compliance is a major determinant of peak oxygen uptake.
AB  - Total arterial compliance (TAC, defined as dV/dP), is a major component of the
      arterial system. A decreased TAC increases left ventricular load and has a
      detrimental effect on coronary perfusion. We sought to assess the influence of
      TAC on the functional reserve (VO2max). Fourteen patients (mean age 64 +/- 14y)
      with known or suspected coronary artery disease and eleven controls (34 +/- 5y)
      underwent supine bicycle exercise echocardiography. Audio Doppler signal output
      of the echocardiographic machine was digitized with a customized hardware and
      software interface simultaneously with carotid tonometry and ECG. TAC at rest was
      calculated by the pulse pressure method (PPM). By step-wise forward multivariate
      analysis, independent predictors of VO2max were patient versus control status,
      peak exercise cardiac output and TAC. The described PC-based acquisition system
      for tonometry and Doppler signals permits the assessment of ventricular function
      and arterial biomechanics.

PMID- 14640119
TI  - Gene symbol: IRF6. Disease: Van der Woude syndrome.

PMID- 14640120
TI  - Gene symbol: IRF6. Disease: Van der Woude syndrome.

PMID- 14640121
TI  - Gene symbol IRF6. Disease: Van der Woude syndrome and popliteal pterygium.

PMID- 14640123
TI  - Cumulative subject index and contributor index, volume 53-71.

PMID- 14640122
TI  - Gene symbol: IRF6. Disease: Van der Woude syndrome.

PMID- 14640124
TI  - Abstracts of the Proceedings of the Nutrition Society. 27-28 March 2003, 18-20
      June 2003, 7-10 July 2003.

PMID- 14640125
TI  - Abstracts of the North American Spine Society 16th Annual Meeting. Seattle,
      Washington, USA, October 31-November 3, 2001.

PMID- 14640126
TI  - Abstracts of the North American Spine Society 17th Annual Meeting. Montreal,
      Canada, October 29-November 2, 2002.

PMID- 14640128
TI  - [Abstracts of the 78th Annual Meeting of the French Society of Orthopedic and
      Trauma Surgery].

PMID- 14640127
TI  - Abstracts of the 18th North American Spine Society 18th Annual Meeting. San
      Diego, California, USA, October 21-25, 2003.

PMID- 14640129
TI  - ECTRIMS 2003. Abstracts of the 19th Congress of the European Committee for
      Treatment and Research in Multiple Sclerosis. September 17-20, 2003, Milan,
      Italy.

PMID- 14640131
TI  - Summaries for students, patients and general readers.

PMID- 14640130
TI  - Aluminium in life: from acid rain to Alzheimer's Disease. Proceedings of the
      Fifth Keele Meeting on Aluminium. February 23-25, 2003. Stroke-on-Trent, United
      Kingdom.

PMID- 14640132
TI  - Abstracts of the 6th Annual NewEra Cardiac Care: Innovation & Technology. January
      3-5, 2003. Dana Point, California, USA.

PMID- 14640133
TI  - Off-pump coronary artery bypass surgery is associated with reduced  neutrophil
      activation as measured by the expression of CD11b: a  prospective randomized
      study.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) surgery is associated with
      systemic inflammation. Activation of neutrophils is a crucial step in
      inflammation and results in neutrophil sequestration within the tissues. One of
      the potential advantages of performing off-pump coronary artery bypass (OPCAB)
      surgery is the attenuation of the systemic inflammatory response. This
      prospective randomized study compares neutrophil activation in patients
      undergoing OPCAB versus those undergoing CABG with cardiopulmonary bypass (CPB).
      METHODS: Twenty patients undergoing primary isolated CABG were randomly divided
      prospectively into 2 groups: 1 group underwent CABG with CPB, and the other group
      underwent OPCAB. Central venous blood samples were obtained before skin incision
      and at 15 minutes, 60 minutes, 2 hours, 5 hours, and 24 hours following the
      initiation of CPB or application of the stabilization device. Differential white
      cell counts were measured with routine laboratory techniques. CD11b surface
      expression on neutrophils was measured by flow cytometry. Interleukin 8 levels in
      the plasma were measured by enzyme-linked immunosorbent assays. RESULTS: The 2
      groups were matched with respect to preoperative and operative characteristics.
      White cell and neutrophil counts rose in both groups following the operation but
      were significantly higher in the OPCAB group at 5 hours (P < .001 and P = .002,
      respectively). Interleukin 8 concentrations were significantly higher in the CPB
      group at 5 hours following the initiation of CPB (P = .034). CD11b levels were
      significantly higher in the CPB group at 60 minutes (P = .002). CONCLUSION: This
      prospective randomized study demonstrates that the activation of circulating
      neutrophils as measured by CD11b expression is lower following OPCAB than in CPB.
      Although OPCAB is associated with significantly higher neutrophil counts, these
      neutrophils exhibit fewer activation markers. The lower postoperative neutrophil
      counts occurring in the CPB group may be explained by the activation and
      consequent sequestration of the neutrophils in the CPB circuit and tissues.

PMID- 14640134
TI  - [Congenital adrenal hyperplasia conditioned by 21beta-hydroxylase deficiency -
      clinical considerations].
AB  - The authors of the paper present three cases of nonclassical forms of congenital
      adrenal hyperplasia conditioned by 21 beta-hydroxylase deficiency occuring within
      the same family. They point out significant difficulties related to the detection
      of such anomalies, and they analyse in detail clinical symptoms occuring in this
      disease entity.

PMID- 14640135
TI  - Abstracts of the 8th World Congress on Advances in Oncology and the 6th
      International Symposium on Molecular Medicine. 16-18 October 2003, Hersonissos,
      Greece.

PMID- 14640136
TI  - Proceedings of the 4th International Workshop on Interventional Pediatric
      Cardiology. Milan, Italy, 2-5 April 2003.

PMID- 14640137
TI  - [Abstracts of the 9th SIN National Congress. Napoli, Italy, 21-24 May 2003].

PMID- 14640138
TI  - Abstracts of the 34th World Conference on Lung Health of the International Union
      Against Tuberculosis and Lung Disease (IUATLD). Paris, France, 29 October-2
      November 2003.

PMID- 14640140
TI  - EVER 2003. Abstracts of the European Association for Vision and Eye Research
      Meeting. October 8-11, 2003, Alicante, Spain.

PMID- 14640139
TI  - [Abstracts of the 27th Fall Meeting of the German Society of Cardiology and
      Cardiovascular Research. 16-18 October 2003, Munster, Germany].

PMID- 14640141
TI  - [2003 German Pain Conference. Munster, Germany, 8-12 October 2003. Abstracts].

PMID- 14640142
TI  - The expert consensus guideline series. Optimizing pharmacologic treatment of
      psychotic disorders. Introduction: methods, commentary, and summary.
AB  - OBJECTIVES: A growing number of atypical antipsychotics are available for
      clinicians to choose from in the treatment of psychotic disorders. However, a
      number of important questions concerning medication selection, dosing and dose
      equivalence, and the management of inadequate response, compliance problems, and
      relapse have not been adequately addressed by clinical trials. To aid clinical
      decision-making, a consensus survey of expert opinion on the pharmacologic
      treatment of psychotic disorders was undertaken to address questions not
      definitively answered in the research literature. METHOD: Based on a literature
      review, a written survey was developed with 60 questions and 994 options.
      Approximately half of the options were scored using a modified version of the
      RAND 9-point scale for rating the appropriateness of medical decisions. For the
      other options, the experts were asked to write in answers (e.g., average doses)
      or check a box to indicate their preferred answer. The survey was sent to 50
      national experts on the pharmacologic treatment of psychotic disorders, 47 (94%)
      of whom completed it. In analyzing the responses to items rated on the 9-point
      scale, consensus on each option was defined as a non random distribution of
      scores by chi-square "goodness-of-fit"test. We assigned a categorical rank (first
      line/preferred choice,second line/alternate choice, third line/usually
      inappropriate) to each option based on the 95% confidence interval around the
      mean rating. Guideline tables indicating preferred treatment strategies were then
      developed for key clinical situations. RESULTS: The expert panel reached
      consensus on 88% of the options rated on the 9-point scale. The experts
      overwhelmingly endorsed the atypical antipsychotics for the treatment of
      psychotic disorders. Risperidone was the top choice for first-episode and multi
      episode patients, with the other newer atypicals rated first line or high second
      line depending on the clinical situation. Clozapine and a long-acting injectable
      atypical (when available)were other high second line options for multi-episode
      patients. The expert's dosing recommendations agreed closely with the package
      inserts for the drugs, and their estimates of dose equivalence among the
      antipsychotics followed a linear pattern. The experts considered 3-6 weeks an
      adequate antipsychotic trial, but would wait a little longer (4-10 weeks) before
      making a major change in treatment regimen if there is a partial response. The
      experts recommended trying to improve response by increasing the dose of atypical
      and depot antipsychotics before switching to a different agent; there was less
      agreement about increasing the dose of conventional antipsychotics before
      switching, probably because of concern about side effects at higher doses. If it
      is decided to switch because of inadequate response, risperidone was the expert's
      first choice to switch to, no matter what drug was initially tried. Although
      there was some disparity in the expert's recommendations concerning how many
      agents to try before switching to clozapine, the expert's responses suggest that
      switching to clozapine should be Clozapine was also the antipsychotic of choice
      for patients with suicidal behavior. When switching oral antipsychotics,the
      experts considered cross-titration the preferred strategy. When switching to an
      injectable antipsychotic, the experts stressed the importance of continuing the
      oral antipsychotic until therapeutic levels of the injectable agent are achieved.
      The experts considered psychosocial interventions the first choice strategy for
      partially compliant patients, with pharmacologic interventions the first choice
      for patients with clear evidence of noncompliance. However, because it can be
      difficult to distinguish partially compliant from noncompliant patients, the
      editors recommended combining psychosocial and pharmacologic interventions to
      improve compliance whenever possible. When patients relapse because of compliance
      problems or if there is any doubt about compliance, the experts recommended the
      use of a long-acting injectable antipsychotic and would select an injectable
      atypical when this option becomes available. The experts would also consider
      using an injectable atypical antipsychotic (when available) in many clinical
      situations that do not involve compliance problems. The experts stressed the
      importance of monitoring for health problems-especially obesity, diabetes,
      cardiovascular problems,HIV risk behaviors, medical complications of substance
      abuse, heavy smoking and its effects, hypertension, and amenorrhea-in patients
      being treated with antipsychotics. Although many patients are prescribed
      adjunctive treatments,multiple antipsychotics, and combinations of different
      classes of drugs (e.g., antipsychotics plus mood stabilizers or antidepressants)
      in an effort to enhance response, the experts gave little support to any of these
      strategies, with the exception of antidepressants for patients with
      dysphoria/depression, antidepressants or ECT for patients with suicidal behavior,
      and mood stabilizers for patients with aggression/violence. When asked about
      indicators of remission and recovery, the experts considered acute improvement in
      psychotic symptoms the most important indicator of remission, whereas they
      considered more sustained improvement in multiple outcome domains (e.g.,
      occupational/educational functioning, peer relationships,independent living)
      important in assessing recovery. CONCLUSIONS: The experts reached a high level of
      consensus on many of the key treatment questions in the survey. Within the limits
      of expert opinion and with the expectation that future research data will take
      precedence, these guidelines provide direction for addressing common clinical
      dilemmas that arise in the pharmacologic treatment of psychotic disorders. They
      can be used to inform clinicians and educate patients regarding the relative
      merits of a variety of interventions. Clinicians should keep in mind that no
      guidelines can address the complexities involved in the care of each individual
      patient and that sound clinical judgment based on clinical experience should be
      used in applying these recommendations.

PMID- 14640143
TI  - The expert consensus guideline series. Optimizing pharmacologic treatment of
      psychotic disorders.

PMID- 14640144
TI  - [Thrombosis of internal and external cerebral veins].

PMID- 14640145
TI  - Congenital absence of the vermiform appendix.

PMID- 14640146
TI  - Validity and completeness of death reporting and registration in a rural district
      of Vietnam.
AB  - AIMS: Assessment was made of the validity of mortality estimates based on data
      collected during 1999-2000 by quarterly follow-up visits and compared with other
      methods (re-census, communal death registration, and neighbourhood survey).
      METHODS: This study was carried out within a longitudinal epidemiological
      laboratory in Bavi, District, Vietnam (called FilaBavi), covering a sample of
      11,089 households with 51,024 inhabitants. Deaths within FilaBavi during 1999
      2000 were collected by four methods and compared: quarterly household follow-ups,
      the re-census carried out in 2001, the Commune Population Registration System
      (CPRS), and a neighbourhood survey. RESULTS: Within these four methods, a total
      of 471 deaths were detected in the FilaBavi sample. Quarterly household follow
      ups detected 470 deaths (99.8%). The re-census missed 19 deaths, of which eight
      were infants, and two-thirds of the missed deaths fell in 1999. The CPRS missed
      89 cases (19%), the majority being infant and elderly deaths. The neighbourhood
      survey over-reported deaths. CONCLUSIONS: Quarterly follow-ups were the best
      method for death registration. The re-census approach was less complete, with
      problems of recall bias. The completeness and quality of death registration by
      CPRS was low, especially for infant and elderly mortality.

PMID- 14640148
TI  - Oral implants in compromised patients.

PMID- 14640147
TI  - Gynecological cancers: a challenge of individualized therapy in the adjuvant and
      palliative setting.

PMID- 14640149
TI  - [70 years of medical services of Airborne Forces].

PMID- 14640150
TI  - Oral health promotion for our ageing Australian population.
AB  - The ageing Australian population living in the new millennium has dental needs
      that are very different and more complex than those experienced by previous older
      adult cohorts during the twentieth century. A summary of the oral health status
      of older Australians is presented, together with a review of the important
      relationships between general health and oral health. The key to maintaining and
      improving older adults' oral health status is the use of oral health promotion
      strategies that focus not only on dental characteristics, but also on the life
      characteristics of older adults, and on their quality of life issues.
      Traditionally, there has been very limited geriatric oral health promotion, with
      several myths contributing to this situation. Contemporary geriatric oral health
      promotion in the new millenium has an evidence-based and planned approach. It
      encompasses not only the treatment of oral diseases and conditions, but has an
      increased focus on the prevention of oral diseases and conditions to enhance oral
      health status and older adults' quality of life. Using the Ottawa Charter and a
      functional dependence classification, a geriatric oral health promotion matrix is
      presented, using a specific example of Australian residential care.

PMID- 14640151
TI  - Edentulism and associated factors in people 60 years and over from urban, rural
      and remote Western Australia.
AB  - BACKGROUND: Edentulism is declining in the aged, in turn increasing demand on
      dental services. The aim of this study was to describe the pattern of edentulism
      and associated factors for people 60 years or over in urban, rural and remote
      Western Australia. METHODS: A cross-sectional telephone interview survey was
      conducted of 2100 people aged 60 years or over (urban n=800, rural n=800, remote
      n=500), identified through the State Electoral Roll, who were living in non
      institutionalized accommodation in Western Australia and who were able to speak
      English sufficiently well to be interviewed in English. RESULTS: The main outcome
      measure was edentulism. The prevalence of edentulism was 25 per cent for people
      in urban areas, 34 per cent for people in rural areas and 32 per cent for people
      in remote areas. Respondents aged 60-69 years had less than half the edentulism
      than respondents aged 80 years or over. Multivariable logistic regression models
      showed geographic location, age, gender, education and occupation were
      significantly associated with edentulism. CONCLUSIONS: The percentage of
      edentulism was highest in rural areas with some clear demographic trends. These
      future aged cohorts are likely to follow the same patterns of social and
      geographic disadvantage as found for the current edentate cohort. The results
      were consistent with other studies while providing state level multivariate
      results to assist service planning.

PMID- 14640152
TI  - Tooth wear prevention: a quantitative and qualitative in vitro study.
AB  - BACKGROUND: Management of tooth wear from grinding presents a significant
      clinical challenge. Acrylic nightguards are often used to protect the teeth, but
      many patients still grind with these appliances. This study aimed to test the
      effectiveness of three lubricants in reducing enamel wear by using an electro
      mechanical machine under controlled conditions, with a view to undertaking a
      subsequent longitudinal clinical study. METHODS: Sectioned tooth specimens were
      worn against each other under different loads and with the addition of three
      different lubricants: calcium fluoride (CaF) powder, olive-oil, and a combination
      of calcium fluoride with olive-oil in the form of a slurry. Wear rates of enamel
      only were quantified by weighing the specimens, and resin replicas of the worn
      tooth surfaces were made for examination under a scanning electron microscope.
      RESULTS: All three lubricants reduced the amount of enamel wear significantly
      compared with wearing specimens without adding lubricants. Wear rate was
      influenced by the type of lubricant and the load applied. Wear rates were
      significantly less for olive-oil and the olive-oil/CaF slurry compared with CaF
      alone. The microwear detail differed between the three lubricants. CONCLUSIONS:
      This study has shown that enamel wear can be reduced using dry or wet lubricants
      between opposing teeth that are worn under controlled conditions. Further
      research is required to clarify their possible clinical applications.

PMID- 14640153
TI  - A survey of sodium hypochlorite use by general dental practitioners and
      endodontists in Australia.
AB  - BACKGROUND: Sodium hypochlorite is used commonly as an endodontic irrigant, but
      there are no published reports that provide details of its use. This survey
      sought to determine the percentage of Australian dentists who practiced
      endodontics, whether they used sodium hypochlorite for irrigation, and the manner
      of dilution, storage and dispensing sodium hypochlorite used by both dentists and
      endodontists. METHODS: All Australian endodontists and a stratified random sample
      of 200 general dentists in Australia were surveyed to address the issues
      identified above. RESULTS: Almost 98 per cent of dentists surveyed performed
      endodontic treatment. Among endodontists, nearly 94 per cent used sodium
      hypochlorite for irrigation compared with just under 75 per cent of general
      dentists. Sodium hypochlorite use by general dentists was more common in Victoria
      and South Australia than in other States. An infant sanitizer (Milton or
      Johnson's Antibacterial Solution) was used by just over 92 per cent of general
      practitioners and by more than 67 per cent of endodontists. All other respondents
      used domestic bleach. One hundred and sixty four of the respondents (80 per cent
      of endodontists and over 90 per cent of general dentists) used a 1 per cent w/v
      solution. Ten practitioners used a 4 per cent w/v solution, five used a 2 per
      cent w/v solution and four used a 1.5 per cent w/v solution. Eighty per cent of
      the practitioners who diluted their sodium hypochlorite before use, used
      demineralized water for this purpose. The remainder used tap water. Only four
      practitioners stored sodium hypochlorite in a manner which risked light exposure
      and loss of available chlorine content. CONCLUSIONS: Sodium hypochlorite is
      commonly used as an endodontic irrigant and Australian dentists generally stored
      the material correctly.

PMID- 14640154
TI  - Social and behavioural determinants of early childhood caries.
AB  - BACKGROUND: To investigate the association between selected social and
      behavioural (infant feeding and preventive dental practices) variables and the
      presence of early childhood caries in preschool children within the north
      Brisbane region. METHODS: A cross sectional sample of 2515 children aged four to
      five years were examined in a preschool setting using prevalence (percentage with
      caries) and severity (dmft) indices. A self-administered questionnaire obtained
      information regarding selected social and behavioural variables. The data were
      modelled using multiple logistic regression analysis at the 5 per cent level of
      significance. RESULTS: The final explanatory model for caries presence in four to
      five year old children included the variables breast feeding from three to six
      months of age (OR=0.7, CI=0.5, 1.0), sleeping with the bottle (OR=1.9, CI=1.5,
      2.4), sipping from the bottle (OR=1.6, CI=1.2, 2.0), ethnicity other than
      Caucasian (OR=1.9, CI=1.4, 2.5), annual family income dollars 20,000-dollars
      35,000 (OR=1.7, CI=1.3, 2.3) and annual family income less than dollars 20,000
      (OR=2.1, CI=1.5, 2.8). CONCLUSIONS: A statistical model for early childhood
      caries in preschool children within the north Brisbane region has been
      constructed using selected social and behavioural determinants. Epidemiological
      data can be used for improved public oral health service planning and resource
      allocation within the region.

PMID- 14640155
TI  - Oral health status of prison inmates--New South Wales, Australia.
AB  - BACKGROUND: This paper assesses the oral health status in a prison population and
      identifies risk factors associated with oral health. METHODS: Cross-sectional
      stratified random sample of 789 prisoners (657 males and 132 females) from 27
      correctional centres across New South Wales, stratified by sex, age and
      aboriginality. A face to face interview was used to collect information on health
      status and behavioural risk factors. A subset of participants (312 males and 22
      females) received an oral examination which enabled the decayed, missing or
      filled permanent teeth (DMFT) score to be calculated. RESULTS: In the last 12
      months 391 (50 per cent) inmates had visited a dentist. Reports on treatment
      received at this last visit were mainly for dental examinations, (62 per cent),
      dental fillings, (38 per cent), and dental extractions (28 per cent). Self
      reported dental needs indicated that 42 per cent perceived the need for a check
      up; the perceived need for dental fillings was highest in females compared with
      males. The mean DMFT for the population was 20.4 and 3.4 for decayed teeth.
      CONCLUSIONS: This survey demonstrates that the standard of past oral health care
      for prison inmates is low. There is a need to be more attentive to oral health
      promotion as eventually respondents will be returning to the community.

PMID- 14640156
TI  - New standards for permanent tooth emergence in Australian children.
AB  - BACKGROUND: Published standards for permanent tooth emergence in Australian
      children are 40 years old. The aim of this study was to present new data on the
      timing and sequence of permanent tooth emergence in a large sample of Australian
      children and to compare the findings with those of earlier studies. METHODS:
      Records of a randomly selected sample of 8676 children, aged between 4 to 16
      years, who had attended the clinics of the South Australian Dental Service were
      scanned optically and coded to provide the data for this study. A logistic
      regression analysis enabled median times of emergence, together with percentile
      ranges, to be calculated for each tooth, except third molars, in boys and girls.
      Comparisons were made between the sexes and with previously published values. The
      frequencies of occurrence of emergence polymorphisms for different tooth pairs
      were also computed. RESULTS: The earliest teeth to emerge in both boys and girls
      were the central incisors and first molars, whereas the second premolars and
      molars and maxillary canines tended to be last to emerge. The mandibular teeth
      tended to precede the corresponding maxillary teeth in emergence in both sexes.
      Tooth emergence was advanced in girls compared with boys, averaging 4.5 months in
      the maxilla and 5.3 months in the mandible. In general, emergence times of
      children in the present sample were later than those reported previously for
      Australian children. The most common emergence polymorphism in the maxilla
      involved the canine and second premolar, whereas common polymorphisms in the
      mandible were noted for the central incisor and first molar, canine and first
      premolar, and the second premolar and second molar. CONCLUSIONS: Given that they
      have been collected relatively recently from a large sample of children, the new
      data reported in this paper can now be used as standards when assessing permanent
      tooth emergence of Australian children.

PMID- 14640157
TI  - Diagnostic and preventive service trends in private general practice: 1983-1984
      to 1998-1999.
AB  - BACKGROUND: Aggregate trends have indicated increases in the provision of
      diagnostic and preventive services but there have been few reports based on their
      component sub-categories. The aims of this study were to investigate time trends
      in the provision of sub-categories of diagnostic an preventive services across a
      15-year period. METHODS: A random sample of Australian dentists was surveyed by
      mailed questionnaire in 1983-1984, 1988-1989, 1993-1994 and 1998-1999 (response
      rates 71-75 per cent). Data were weighted to provide representative estimates for
      the age by sex distribution of private general practitioners in 1983, 1988, 1993
      and 1998. RESULTS: Rates per visit were higher, Poisson regression, P<0.05, in
      1998-1999 compared to baseline for examinations, radiographs, prophylaxis and
      topical fluoride. Diagnostic and preventive service rates varied by age of
      patient: compared to patients aged 65+ years, examinations were higher among
      children aged <5 years to adults aged 25-44 years, radiographs were lower among
      children <5 years and 5-11 years but higher among adults aged from 18-24 years to
      45-64 years, prophylaxis services were lower among children <5 years but higher
      among adolescents 12-17 years to adults aged 45-64 years, while topical fluoride
      was higher among children 5-11 years and adolescents 12-17 years. CONCLUSIONS:
      Examination, radiograph, prophylaxis, and topical fluoride rates increased over
      the study period. While examination rates increased for both children and adults,
      and prophylaxis rates increased for adolescents and adults, rates for radiographs
      and topical fluoride only increased for adults. Age-specific changes in service
      rates over time indicate the effect of changing oral health status and population
      demographics on service provision.

PMID- 14640158
TI  - Tongue cancer: do patients younger than 40 do worse?
AB  - BACKGROUND: Debate continues as to whether being young confers a worse prognosis
      for patients with squamous cell carcinoma of the tongue. Recent papers have
      provided conflicting views in this debate. In this study we aimed to investigate
      if young age at the time of diagnosis of squamous cell carcinoma of the tongue
      confers a worse prognosis. METHODS: Eligible patients were identified through the
      computer database of the Department of Radiation Oncology, Westmead Hospital,
      Sydney. All eligible patients were treated with radical intent. Using age 40 as a
      cut off multivariate and survival analysis was undertaken to compare age groups.
      RESULTS: Median age at diagnosis was 60 years (range, 19-86 years) in 84 males
      (65 per cent) and 45 females (35 per cent). Median follow-up time was 43 months
      (range, 2.3-203 months). Fifteen patients (12 per cent) were aged <40 years. On
      univariate analysis stage and age were significant determinants of disease
      specific survival. There was no difference in overall survival between the young
      (<40 years) and middle-aged groups (40-60 years). However, the young and the
      middle aged were both more likely to survive than the older age group (>60
      years). On multivariate analysis age remained a significant factor for
      determining disease-specific survival, with the older age group 2.9 times more
      likely to die than the younger groups. CONCLUSION: Young age (<40 years) did not
      portend to worse survival in comparison to older tongue cancer patients.

PMID- 14640159
TI  - Implant-supported titanium prostheses following augmentation procedures: a
      clinical report.
AB  - BACKGROUND: This report describes a novel technique for fabricating retrievable
      implant-supported titanium (Ti) prostheses in patients requiring a comprehensive
      treatment plan involving the combined efforts of maxillofacial surgery and
      implant prosthodontics. METHODS: Following bone graft reconstructive surgery and
      implant placement prosthetic treatment was initiated by inserting ITI-Octa
      abutments. An impression was made, and a framework was fabricated by fusing Ti
      cast frameworks to prefabricated titanium copings by laser-welding. This was
      followed by veneering or fabrication of a removable denture with Ti metal re
      enforcement. RESULTS: Favourable clinical results have been achieved using these
      screw-retained Ti implant-supported restorations for patients treated with
      reconstructive bone graft-surgery, with clinical observation periods ranging from
      three to four years. CONCLUSIONS: The present observations suggest that these
      screw-retained implant-supported Ti prostheses may be a meaningful contribution
      to implant prosthodontics, facilitating retrievable restorations of optimum
      biocompatibility, good marginal precision and with a good esthetic result.
      However, controlled clinical studies are needed to establish the long-term
      serviceability of these Ti restorations.

PMID- 14640160
TI  - Oral ulceration with bone sequestration.
AB  - Oral mucosal ulceration is a common manifestation of various disease processes.
      Identification of the aetiological factor(s) involved greatly facilitates the
      management of such conditions. This report describes oral ulceration of the
      mucosa overlying the lingual shelf and mylohyoid ridge of the mandible and, less
      commonly on tori and exostoses, in association with bone sequestration. Trauma,
      which involves the subjacent periosteum resulting in a focus of ischaemic bone
      necrosis, in conjunction with local anatomical and perhaps other systemic
      predisposing factors, forms the aetiopathogenesis for this particular type of
      focal ulcerative lesion.

PMID- 14640161
TI  - Intra-alveolar distraction osteogenesis in preparation for dental implant
      placement combined with orthodontic/orthognathic surgical treatment: a case
      report.
AB  - The use of implants has become a routine part of restorative dental treatment.
      The placement of implants requires a sufficient quantity of bone in which to
      place implant fixtures. Where such bone does not exist, a number of methods have
      been used to augment the affected area of the alveolar ridge. This case report
      describes the use of the relatively new distraction osteogenesis procedure to
      increase bone volume in a patient who required post-traumatic restoration of
      several missing teeth, as well as comprehensive orthodontic and orthognathic
      surgical treatment.

PMID- 14640162
TI  - Dentist's management of medical emergencies.

PMID- 14640163
TI  - Laparoscopic appendicectomy.

PMID- 14640164
TI  - Laparoscopic appendicectomy at the Aga Khan Hospital, Nairobi.
AB  - OBJECTIVE: To evaluate our experience of laparoscopic appendicectomy at the Aga
      Khan Hospital, Nairobi over a six year period from the inception of the technique
      and to assess its advantages and disadvantages. DESIGN: Case series study.
      SETTING: The Aga Khan Hospital, Nairobi. PATIENTS: One hundred and six cases
      operated on from May 1996 to June 2002. MAIN OUTCOME MEASURES: Clinical
      presentation, age and sex demographics, average hospital stay, operating time,
      intra-operative and post-operative complications and outcome. RESULTS: There was
      a female preponderance with a female to male ratio of 2:3:1. Mean age was 30.6
      years. There was a slightly more number of patients with recurrent appendicitis
      as opposed to the acute form. Totally laparoscopic procedure was in 39.6% of the
      cases, laparoscopic assisted in 45.3%. The conversion rate to an open procedure
      was 15.1%. Post operative port-site infection was 8.5%. No mortality was reported
      in these series. However there was one case which required re-operation following
      significant port site haemorrhage. Mean post-operative hospital stay was 2.2
      days. CONCLUSION: Laparoscopic appendicectomy is a safe procedure in well trained
      hands. The major advantages are less morbidity and excellent cosmesis. Discovery
      of other intraabdominal pathologies is possible through laparoscopy as opposed to
      classical appendicectomy.

PMID- 14640165
TI  - Gastro-intestinal tract perforation in neonates.
AB  - BACKGROUND: Gastro-intestinal tract (GIT) perforation in neonates is a serious
      problem associated with high mortality due to resulting sepsis. Co-morbid
      factors, eg. prematurity, respiratory problems, low birth weight, and nutritional
      factors, negatively affect the outcome. OBJECTIVES: To review the management
      outcome of gastro-intestinal tract perforation in neonates in KwaZulu-Natal and
      identify factors that require attention for better survival of neonates with GIT
      perforation. DESIGN: Retrospective study of consecutive complete data sets of
      patients presenting with a diagnosis of GIT perforation. SETTING: Department of
      Paediatric Surgery, Nelson R. Mandela School of Medicine, University of Natal,
      Durban, South Africa. SUBJECTS: Fifty four neonates treated for gastro-intestinal
      tract perforation between January 1998 and January 2003. MAIN OUTCOME MEASURES:
      Morbidity as determined by complications and mortality. RESULTS: More males (69%)
      were affected than females (31%). The median birth weight was 2.3 kg and median
      age at presentation was four days. Eighty nine percent were referred from
      peripheral hospitals. Abdominal distension was the leading symptom and sign
      (74%). Co-morbid factors were present in 89%, with prematurity as the leading
      factor (52%). Necrotising enterocolitis (NEC) was the main cause of perforation
      (33%) and the terminal ileum was the most common site. Most (56%) were treated by
      excision and primary repair of perforations. Sepsis was the leading complication
      (44%) and major cause of death (72%). Mortality was highest (56%) in perforations
      due to other primary pathology followed by NEC (53%). Overall mortality was 46%.
      CONCLUSION: It is essential to prevent secondary perforations by early
      recognition and management of primary pathology. Management of pneumoperitoneum
      in neonates with respiratory difficulties should be included in resuscitation
      before transfer. Rectal temperature monitoring and herbal enemas should be
      strongly discouraged.

PMID- 14640166
TI  - Neonatal bacterial meningitis at the newborn unit of Kenyatta National Hospital.
AB  - BACKGROUND: Meningitis occurs in up to one third of neonates with septicaemia.
      Diagnosis is difficult due to its non-specificity of signs and symptoms. While
      neonatal septicaemia is a common problem at Kenyatta National Hospital (KNH),
      there are no recent data on the incidence and clinical characteristics of
      neonatal meningitis at the hospital. OBJECTIVE: To evaluate the prevalence and
      the bacterial aetiology of meningitis in neonates at the Newborn Unit (NBU) of
      KNH. DESIGN: Descriptive cross-sectional study. SETTING: Newborn Unit of Kenyatta
      National Hospital, Nairobi, Kenya. SUBJECTS AND METHODS: Lumbar punctures were
      performed on eighty-four neonates with suspected sepsis based on specified
      clinical criteria. Cases were defined as meningitis if the cerebrospinal fluid
      (CSF) was positive for bacteria by Gram stain, aerobic bacterial culture or latex
      particle agglutination assay. RESULTS: The prevalence of meningitis amongst cases
      of suspected sepsis was 17.9%. The male:female ratio was 1.5:1 mean birth weight
      2116.7 grams (1682.2-2551.2) mean gestational age 35.7 weeks (32.6-38.8) and the
      mean postnatal age was 4.1 days (2.7-5.4) with none of the parameters being
      significantly different from those without meningitis. Feed intolerance and
      lethargy were the most common clinical features, present in 73.3% and 60% of
      patients with meningitis respectively. Neonates with meningitis had a higher mean
      CSF protein value (2.67 g/L vs 1.97 g/L, p=0.367) and a significantly higher mean
      CSF white cell count (21 cells/mL vs 7 cells/mL, p=0.001). The most common
      aetiological agents were Escherichia coli (46.7%). Group B. Streptococci (26.7%)
      and Klebsiella pneumoniae (13.3%). Most blood and CSF isolates were resistant to
      ampicillin and gentamicin but showed good in-vitro sensitivities to amikacin,
      cefuroxime and the third generation cephalosporins (ceftriaxone, ceftazidime and
      cefotaxime). Blood cultures were positive in only 53.3% of neonates with
      meningitis. CONCLUSION: Neonatal bacterial meningitis is an important clinical
      problem at KNH with a prevalence of 17.9% amongst cases of suspected sepsis. E.
      coli and Group B Streptococci were the most common aetiological pathogens. Blood
      cultures were negative in almost half of the patients with meningitis. Resistance
      to the commonly employed first-line antibiotics (penicillin and gentamicin) is
      high and a change of empirical antibiotic use for neonates with suspected sepsis
      is recommended.

PMID- 14640167
TI  - Community and facility surveys illuminate the pathway to child survival in Liben
      Woreda, Ethiopia.
AB  - OBJECTIVES: To apply "Pathway to Survival" analysis to baseline assessments to
      inform integrated management of childhood illness programmes. DESIGN: A cross
      sectional survey evaluating community-based knowledge, practices and coverage and
      health facility quality. SETTING: Liben Woreda (population 122, 410), a district
      in Borana Zone, of Ethiopia's Oromia region, from August 1997-Febuary 1998.
      SUBJECTS: Three hundred and sixty eight mother-child pairs (age < 24 months) seen
      in the community and 28 children (age < 5 years) in health facilities. RESULTS:
      Of the 368 mothers interviewed 50% reported that their child was ill in the
      previous two weeks (184/368). Amongst the 101 mothers of children under the age
      of six months only 24% reported exclusive breast-feeding (24/101). There were 194
      children who should have completed their immunisation schedule; only 17% of them
      had done so (33/194). Amongst the 111 children who had diarrhoea, only 17% had
      received home treatment with ORS (19/111). Thirty per cent of mothers of children
      with possible pneumonia (25/83) and 28% who reported malaria (14/50) sought
      appropriate care. Amongst those caregivers seen at the health facility only 26%
      had an understanding of treatment recommendations. CONCLUSIONS: Based on the
      pathway to survival analysis, mother's knowledge of illness recognition is
      limited and they practice both home care and care seeking poorly. Thus few
      children are likely to receive and comply with standard case management.

PMID- 14640168
TI  - Chronic myeloid leukaemia in central Africans.
AB  - OBJECTIVES: To document the pattern of presenting clinical and haematological
      features of chronic myeloid leukaemia (CML) in central Africans and evaluate the
      clinical consequences of treating the disease with chemotherapy. DESIGN:
      Prospective descriptive analysis of clinical and haematological data. SETTING:
      Departments of Haematology of tertiary referral centres and teaching hospitals.
      MATERIALS AND METHODS: Prospective clinical and haematological data were
      collected on 150 central Africans (90 Zimbabweans and 60 Malawians) using modern
      Coulter counters and standard up-to-date haematological procedures and the
      results analysed using predetermined criteria and the top-desk Scientific
      Calculator Model HP 48GX, Texas Instruments, USA. RESULTS: There were 150 CML
      patients studied. Males predominated in a ratio of 1:5:1. The youngest patient
      was 10 years and the oldest 77 years with a mean +/- s.d. of 38.9 +/- 14.7 years.
      The peak age incidence of 47.3% occurred between 21 to 40 years. The Ph
      chromosome was found in 19 of the 20 patients studied. Although complaints
      attributed to splenic enlargement were the most common symptoms, several unusual
      clinical features were encountered viz: hepatomegaly (26%), bleeding (12%),
      significant lymphadenopathy (11.3%), purpura (3.3%), skin infiltration (2.7%),
      cardiac failure (2.7%) and 14.7% were diagnosed incidentally. Symptoms such as
      fatigue, headaches and weight loss were associated with greater degrees of
      leucocytosis, severe to gross splenomegaly and lower haemoglobin levels. The
      severe to gross splenomegaly which occurred in 68(45.3%) suggests that patients
      in this part of the world seek medical advice rather late in the disease. The
      median survival times of 65,47 and 39 months respectively for alpha interferon,
      hydroxyurea and busulphan are in agreement with those of previous larger series
      from other parts of the world. CONCLUSIONS: The study has revealed that the
      presenting pattern of clinical and haematological features of CML is changing
      probably due to the advent of modern clinical practice coupled with increased
      physician density, greater awareness of disease among clinicians besides other
      reasons. However, optimal treatment is not possible for the majority of patients
      due to lack of chemotherapeutic agents and supportive care. RECOMMENDATION:
      Referral centres in African health systems should be equipped for better
      management of CML patients.

PMID- 14640169
TI  - Vitamin A deficiency among Kenyan children as detected by conjunctival impression
      cytology.
AB  - OBJECTIVE: To determine the prevalence of Xerophthalmia among Kenyan children
      aged four to seven years in high risk using Conjuctival Impression Cytology and
      transfer. DESIGN: A cross sectional community based study. SETTING: Mathare slum
      in Nairobi and Tiva/Ithiani area of Kitui. SUBJECTS: Children aged four to seven
      years residing in the above areas were assessed for both clinical and cytological
      features of vitamin A deficiency. RESULTS: Of the 342 children included in this
      study, 316 (92.0%) were normal, five (1.5%) had XN, 19 (5.9% had XIA and two
      (0.6%) had XIB. No signs of corneal Xerophthalmia were seen in this study.
      Conjuctival impression cytology and transfer (CICT) was used to asses for
      squamous metaplastic changes associated with Vitamin A deficiency (VAD). Seventy
      five (23.1%) of the children were normal by CICT while 249 (76.9%) were abnormal.
      In comparing the two areas of study, only 13.2% of the children in Mathare had
      normal CICT compared to 50% in Kitui. For each of the age groups studied there
      was significant difference between the two areas with children from Mathare being
      more deficient than those from Kitui. CONCLUSION: VAD is a significant health
      problem in the high risk areas assessed by CICT in this study.

PMID- 14640170
TI  - Initial injury care in Nairobi, Kenya: a call for trauma care regionalisation.
AB  - OBJECTIVE: To describe the emergency care of injuries at a main city hospital.
      DESIGN: A prospective study. SETTING: Data were collected between February 1st,
      1999 and 30th April, 1999 from the records of the 2000 bed Kenyatta National
      Hospital (KNH) in Nairobi, Kenya. SUBJECTS: Two hundred and forty injury patients
      admitted at KNH were analysed. METHODS: All patients were analysed for
      demographics, environment of injury hospital arrival and Emergency Department
      times. The effects of injury severity, place of injury and time of day on these
      time intervals were analysed statistically. RESULTS: Road injury admissions
      formed 31% of all injury admissions. The mean age was 30 years. Males comprised
      84.6% of all patients. The proportions of patients under 20 years of age was 20%
      with a peak age of 20-29 years. Majority (43.3%) of the injured resided in
      deprived neighbourhood of East Nairobi. The mean pre-hospital time was 2.56
      hours. The Emergency Department disposition time was 3.36 hours. Injuries of all
      severities, as determined by the Injury Severity Score (ISS), were treated. The
      pace of care did not match severity of the injuries. Only 17.5% reached their
      areas of definitive care within sixty minutes. CONCLUSION: Injuries following
      road traffic accidents (RTAs) are common in Nairobi. The response to injury is
      slow and haphazard. The insitution of a care incorporating the city's health
      centers and pre-hospital triage may optimise care.

PMID- 14640171
TI  - Presentation of primary mediastinal masses in Ibadan.
AB  - OBJECTIVES: To determine clinical features, anatomic location and histological
      types of primary mediastinal masses diagnosed and treated in a black African
      population. DESIGN: A retrospective study of clinical data collected from
      patients case notes, the cardiothoracic unit's and pathology records between June
      1975 and May 1999. SETTING: University College Hospital, Ibadan, Nigeria which
      hosts a major cancer center in the West African sub-region, and serves community
      clinics. PATIENTS: All patients with primary mediastinal masses referred for
      evaluation and treatment. MAIN OUTCOME MEASURES: Excluded metastatic, oesophageal
      and vascular-lesions. All patients had radiological evalulation and tissue
      biopsies. The anatomic subdivision of the mediastinum into anterosuperior, middle
      and posterior section was used. RESULTS: One hundred and five consecutive
      patients were evaluated and treated. The mean age was 34.0 +/- 20.4 years. There
      were 75 males and 30 females. Eighty one (77.1%) were symptomatic, 24 (22.9%)
      were asymptomatic. Thirty seven (45.7%) of the symptomatic patients had malignant
      disease while 44 (54.3%) had benign disease. Forty five patients (43%) and 60
      patients (57%) had malignant and benign diseases respectively. Incidence of
      symptoms, was 82.2% for malignant and 73.3% for benign diseases. This difference
      in incidences is statistically insignificant (p=0.283). Majority of asymptomatic
      patients (70.8%) had benign disease while 29.2% of patients with malignancy were
      asymptomatic. This difference in incidence was statistically significant
      (p=0.0039). The frequency of mediastinal masses were anterosuperior, in 67
      patients (63.8%), posterior mediastinal, 24 patients (22.9%) and middle
      mediastinal in 14 patients (13.3%). Lymphoma 23 (21.9%), thymus glands tumours 19
      (18.1%) and endocrine tumours (goiters) 18 (17.1%) were the commonest types of
      primary mediastinal masses treated. CONCLUSION: Majority of our patients with
      mediastinal masses (whether benign or malignant) are symptomatic and the absence
      of symptoms is more associated with benign disease. Majority of lesions are
      situated in the anterosuperior mediastinum. Lymphoma is the most frequent primary
      mediastinal mass.

PMID- 14640173
TI  - Fournier's gangrene complicating vasectomy.
AB  - Quality of care of services provided to family planning clients is a source of
      major concern in reproductive health care, especially in resource-poor settings.
      It may be measured in terms of safety of the method or service provided and may
      be influenced by the knowledge, skills and experience of the service providers,
      the environment in which the services are provided and the care thereafter. As a
      result of various efforts by the government and other stake-holders there have
      been tremendous developments in the family planning programme in Malawi in the
      past ten or so years. The contraceptive prevalence rate (CPR) more than doubled
      between 1992 and 2000. Secondly there has been expansion of facilities providing
      contraceptive services and the method mix such as introduction of voluntary
      surgical contraception (VSC) for both females and males. The increased demand for
      contraceptive services has outstripped the available services and as a result led
      to lapses in the quality of care. These have resulted in some apparently healthy
      individuals either dying in the course of or following service provision or
      suffering serious morbidities. This paper presents two cases of Fournier's
      gangrene following vasectomy in previously healthy male adults in Malawi. It
      discusses their diverse management and results thereof, and explores the
      potential impact on the programme in Malawi, in the context of adverse publicity
      on contraceptives. The possible operational factors for the complications are
      explored and preventive strategies proposed to ensure sustenance of the already
      registered gains in fertility control in Malawi.

PMID- 14640172
TI  - Plasma magnesium in adult asthmatics at the Lagos University Teaching Hospital,
      Nigeria.
AB  - OBJECTIVE: To determine the plasma magnesium levels in adult asthmatics. DESIGN:
      Case control study. SETTING: Lagos University Teaching Hospital, Lagos, Nigeria.
      SUBJECTS: Forty stable asthmatics and thirty five apparently healthy controls.
      METHODS: Detailed history including drug history was obtained from patients and
      controls. Fasting venous blood was collected into heparinized tubes from both
      patients and controls. Plasma magnesium, albumin, calcium and phosphorus were
      measured using spectrophotometric end point methods. RESULTS: Mean (SD) plasma
      magnesium concentration of 0.93(0.24) mmol/L in the asthmatics was significantly
      lower compared to the controls which was 1.15(0.28) mmol/L, p<0.001. There was no
      significant difference in the plasma albumin, calcium and phosphorus levels
      between the patients and controls. Plasma magnesium levels correlated with the
      plasma albumin level (r=0.62) but did not correlate with the duration of disease,
      peak flow rate and age of patients. There was no gender difference in plasma
      magnesium levels in the asthmatics. CONCLUSION: Adult Nigerian asthmatics have
      lower plasma magnesium concentrations compared to healthy controls. This may be
      of use in future therapeutic management of asthma. A large scale multi-centre
      study needs to be carried out since this study was done in one hospital.

PMID- 14640174
TI  - Anomalies of the renal, phrenic and suprarenal arteries: case report.
AB  - This is a case where multiple anomalies of the posterior abdominal wall arteries
      were found. These were accessory renal, a pre-hilar division of the renal, a
      unilateral origin of the inferior phrenic artery from the renal and aberrant
      suprarenal arteries. The accessory renal and the pre-hilar branch of the renal
      resembled polar arteries that supplied the upper and lower poles and similar
      segments of both kidneys.

PMID- 14640175
TI  - Practice guidelines on the use of bone mineral density measurements: Who to test?
      What measures to use? When to treat? A consensus report from the Middle East
      Densitometry Workshop.

PMID- 14640176
TI  - Abstracts of the Middle East Densitometry Workshop. April 20, 2002, Beirut,
      Lebanon.

PMID- 14640183
TI  - Influence of meiotic inhibition by butyrolactone-I during germinal vesicle stage
      on the ability of porcine oocytes to be activated by electric stimulation after
      nuclear maturation.
AB  - Butyrolactone-I (BL-I) is a specific inhibitor of cyclin-dependent kinases and
      prevents germinal vesicle breakdown (GVBD) in porcine oocytes. This study first
      focused on the effect of BL-I on the time course of GVBD and progression to
      metaphase II (MII) in oocytes after the removal of BL-I. When porcine oocytes
      were treated with 20 microM BL-I for 28 h, the intervals taken to undergo GVBD
      and progress to MII were 4-8 h and 16-20 h after washing out BL-I, respectively.
      These intervals were both approximately 8 h behind those of the control oocytes.
      When the BL-I treatment was performed for 20 h, instead of 28 h, there were no
      differences in the timing or frequency of progression to MII between the BL-I
      treatment and control groups. To determine whether the cytoplasmic maturation was
      the same, the ability of oocytes to form a female pronucleus in response to an
      electric stimulus was examined. When oocytes were stimulated at 28 h after the
      removal of BL-I, the rate of pronucleus formation was significantly lower in
      oocytes treated with BL-I than in untreated oocytes, despite the fact that both
      groups reached MII at a similar time. When the electric stimulus was given at 36
      h after the removal of BL-I, oocytes had a pronucleus formation rate comparable
      to that of control oocytes. Therefore, the findings suggest that BL-I treatment
      of porcine oocytes at the germinal vesicle stage affects not only the progression
      of meiosis, but also the events involved in cytoplasmic maturation.

PMID- 14640184
TI  - Meiotic arrest maintained by cAMP during the initiation of maturation enhances
      meiotic potential and developmental competence and reduces polyspermy of IVM/IVF
      porcine oocytes.
AB  - We investigated effects of invasive adenylate cyclase (iAC), 3-isobutyl-1
      methylxanthine (IBMX) and dibutyryl cyclic AMP (dbcAMP) on porcine oocyte in
      vitro maturation (IVM), in vitro fertilisation (IVF) and subsequent embryonic
      development. Porcine oocytes were collected in Hepes-buffered NCSU-37
      supplemented with or without 0.1 microg/ml iAC and 0.5 mM IBMX. IVM was performed
      in a modified NCSU-37 supplemented with or without 1 mM dbcAMP for 22 h and then
      without dbcAMP for an additional 24 h. After IVF, oocytes were cultured in vitro
      for 6 days. After 12 h of IVM, no difference in nuclear status was observed
      irrespective of supplementation with these chemicals during collection and IVM.
      At 22 h, most (95%) of the oocytes cultured with dbcAMP remained at the germinal
      vesicle (GV) stage, whereas 44.3% of the oocytes cultured without dbcAMP
      underwent GV breakdown. At 36 h, oocytes cultured with dbcAMP had progressed to
      prometaphase I or metaphase I (MI) (32.6% and 49.3%, respectively), whereas non
      treated oocytes had progressed further to anaphase I, telophase I or metaphase II
      (MII) (13.6%, 14.3% and 38.0%, respectively). At 46 h, the rate of matured
      oocytes at MII was higher in oocytes cultured with dbcAMP (81%) than without
      dbcAMP (57%), while the proportion of oocytes arrested at MI was lower when
      cultured with dbcAMP (15%) than without dbcAMP (31%). The rate of monospermic
      fertilisation was higher when oocytes were cultured with dbcAMP (21%) than
      without dbcAMP (9%), with no difference in total penetration rates (58% and 52%,
      respectively). The blastocyst rate was higher in oocytes cultured with dbcAMP
      (32%) than without dbcAMP (19%). These results suggest that a change in
      intracellular level of cAMP during oocyte collection does not affect maturational
      and developmental competence of porcine oocytes and that synchronisation of
      meiotic maturation using dbcAMP enhances the meiotic potential of oocytes by
      promoting the MI to MII transition and results in high developmental competence
      by monospermic fertilisation.

PMID- 14640185
TI  - Comparative morphometry of precompacted bovine embryos produced in vivo or in
      vitro after parthenogenetic activation and intracytoplasmic sperm injection
      (ICSI): ultrastructural analysis.
AB  - Early bovine precompacted embryos (1 to 8 blastomeres) were analysed by electron
      microscopy. The volume density of cellular components was determined by
      morphometric analysis to quantify the ultrastructure of early bovine embryos
      produced either in vivo or in vitro both after fertilisation by intracytoplasmic
      sperm injection (ICSI) or from electrically stimulated oocytes (AC/DC). In normal
      embryos obtained in vivo (control), most of the cellular volume was occupied by
      cytoplasm (82.93%). The relative volume of lipids, vacuoles, mitochondria, Golgi
      apparatus and inclusion bodies was minimal. In the group of embryos after
      parthenogenetic activation (AC/DC) a relatively high proportion of the volume was
      occupied by vacuoles and lipids (18.68% vs 14.33%). Early ICSI-derived embryos
      contained the lowest relative volume of cytoplasm (58.33%) compared with the
      control embryos (in vivo) and parthenogenetically AC/DC-activated embryos and a
      higher volume was occupied by lipids (13.25%) and vacuoles (12.92%). It is
      concluded that in vitro produced embryos have a significantly altered
      ultrastructure, indicating extensive cellular damage.

PMID- 14640186
TI  - The in vitro and in vivo development of goat embryos produced by intracytoplasmic
      sperm injection using tail-cut spermatozoa.
AB  - The objective of this study was to assess the efficacy of a novel
      intracytoplasmic sperm injection (ICSI) procedure, as well as the in vitro and in
      vivo developmental competence of goat embryos produced by ICSI. Oocyte-cumulus
      complexes recovered by LOPU from donors stimulated with gonadotrophins were
      matured in vitro. Fresh goat semen was used for ICSI following Percoll gradient
      washing. Tail-cut spermatozoa were microinjected into the ooplasm of goat oocytes
      using a piezo micropipette-driving system (PiezoDrill). In order to assess
      developmental competence, the ICSI-derived zygotes were cultured in one of two
      media systems (mTALP-mKSOM vs G1.3-G2.3) for in vitro development or were
      transferred into recipients for full-term development. The results suggest that
      cutting sperm tails using the oocyte-holding pipette coupled with the PiezoDrill
      is an efficient approach for goat ICSI in terms of oocyte survival, pronuclear
      development and initial cleavage. The mTALP-mKSOM culture system was more
      suitable for in vitro development of ICSI-derived goat embryos than G1.3-G2.3.
      This first report of full-term development of an ICSI-derived goat embryo
      suggests that ICSI can be applied to assisted reproduction in goats.

PMID- 14640187
TI  - Effect of ejaculate, bull, and a double swim-up sperm processing method on sperm
      sex ratio.
AB  - Offspring gender preselection has applications of considerable economic, health
      and ecological interest. In this study we analysed modifications of the
      percentages of spermatozoa bearing Y and X chromosomes when semen samples are
      submitted to a double swim-up technique as a possible method for producing
      embryos of known sex with in vitro fertilisation protocols. As an initial
      experiment to provide accurate evaluation of the method we determined the
      possible incidence of natural deviations in the primary sex ratio between bulls
      or ejaculates, analysing the percentage of Y-chromosome DNA bearing spermatozoa
      (%Y-CDBS) with a polymerase chain reaction (PCR) amplification of X- and Y
      specific fragments. Ejaculates were tested by direct semiquantitative PCR sexing
      and by sexing blastocysts produced in vitro with these spermatozoa. Bulls and
      ejaculates did not have any effect on the %Y-CDBS or on the sex ratio of embryos
      produced in vitro using these ejaculates. However, our double swim-up sperm
      preparation method produced differences in %Y-CDBS in some of the sperm
      fractions, suggesting that there are intrinsic differences in capacitation of X-
      and Y-bearing spermatozoa that might be used to produce embryos of the desired
      sex with in vitro fertilisation.

PMID- 14640188
TI  - Potential amplification of early pregnancy signals by ovarian follicular cells in
      suspension within the fallopian tube.

PMID- 14640189
TI  - Expression of IGF2 and IGF receptor mRNA in bovine nuclear transferred embryos.
AB  - Incomplete reprogramming of the donor cell nucleus after nuclear transfer (NT)
      probably leads to the abnormal expression of developmentally important genes.
      This may be responsible for the low efficiency of cloned animal production.
      Insulin-like growth factor 2 (IGF2) and IGF2 receptor (IGF2R) are imprinted genes
      that play important roles in preimplantation development. To obtain an insight
      into abnormal gene expression after nuclear transfer, we assessed the
      transcription patterns of IGF2-IGF2R in single in vitro fertilised and cloned
      embryos by reverse-transcription polymerase chain reaction (RT-PCR). IGF2R
      expression did not differ significantly but IGF2 was more highly expressed in
      cloned embryos than in IVF embryos (p < 0.05). This was confirmed by a
      quantitative RT-PCR method. Thus, incomplete reprogramming may induce abnormal
      transcription of IGF2 in cloned embryos.

PMID- 14640190
TI  - Ultrastructural localisation of calcium deposits in pig oocytes maturing in
      vitro: effects of verapamil.
AB  - The culture of pig oocytes in the presence of the calcium channel blocker
      verapamil (0.02 mM) resulted in the blocking of meiosis at the metaphase I stage,
      and only a small fraction (about 28%) of the oocytes were able to continue their
      maturation to the stage of metaphase II. Hence, meiotic maturation in pig oocytes
      is a calcium-dependent process. After isolation of the pig oocytes from their
      follicles, the intracellular calcium deposits in the oocyte and granulosa cells,
      detectable using the combined oxalate-pyroantimonate method, are depleted. The
      amount of calcium deposits in the oocyte and granulosa cells increased during
      oocyte meiotic maturation in vitro, especially in the nucleus, mitochondria,
      vacuoles and cytoplasm. The replenishment of calcium deposits is significantly
      changed under the effect of verapamil. The increase in calcium deposits in the
      oocyte nucleus was delayed, a much larger amount of deposits was formed in the
      mitochondria, and the amount of deposits in the vacuoles was demonstrably
      smaller. A significant peak in the accumulation of calcium deposits was observed
      in the cytoplasm of verapamil-treated oocytes after 16 h of in vitro culture. We
      propose that an altered pattern in the replenishment of calcium deposits can
      disturb intracellular signalling and prevent the exit of oocytes from the
      metaphase I stage.

PMID- 14640191
TI  - Pronucleus formation, DNA synthesis and metaphase entry in porcine oocytes
      following intracytoplasmic injection of murine spermatozoa.
AB  - The onset of pronucleus formation and DNA synthesis in porcine oocytes following
      the injection of porcine or murine sperm was determined in order to obtain
      insights into species-specific paternal factors that contribute to fertilisation.
      Similar frequencies of oocytes with female pronuclei were observed after
      injection with porcine sperm or with murine sperm. In contrast, male pronuclei
      formed 8-9 h following the injection of porcine sperm, and 6-8 h following the
      injection of murine sperm. After pronucleus formation maternally derived
      microtubules were assembled and appeared to move both male and female pronuclei
      to the oocyte centre. A few porcine oocytes entered metaphase 22 h after the
      injection of murine sperm, but normal cell division was not observed. The mean
      time of onset of S-phase in male pronuclei was 9.7 h following porcine sperm
      injection and 7.4 h following mouse sperm injection. Ultrastructural observation
      revealed that male pronuclei derived from murine sperm in porcine oocytes are
      morphologically similar to normal male pronuclei in porcine zygotes. These
      results suggest that species-specific paternal factors influence the onset of
      pronucleus formation and DNA synthesis. However, normal nuclear cytoplasmic
      interactions were observed in porcine S-phase oocytes following murine sperm
      injection.

PMID- 14640192
TI  - Nucleolus in apoptosis-induced mouse preimplantation embryos.
AB  - Apoptosis may occur in early embryos in which the execution of essential
      developmental events has failed. Thus the initiation of the apoptotic mechanism
      may be related to activation of the embryonic genome. In this way,
      developmentally incompetent cells or whole embryos are eliminated. It is likely
      that some link exists between failed resumption of rRNA synthesis and the
      incidence of apoptosis in cleaving embryos. In this context, decreased
      developmental potential in cleaving nucleotransferred embryos is consistent with
      cell loss, and very likely due to programmed cell death. The effects of apoptosis
      inducers on cleaving embryos have not been characterised in comparable detail to
      that in the case of somatic cells. Early embryos provide a very good model for
      study of these processes because of the specificity of rRNA transcription
      resumption after fertilization. In our experiments three apoptosis inducers
      (staurosporin 10 mM, actinomycin D 0.05 mg/ml and camptothecin 0.1 mg/ml) were
      used in a culture medium for 15 h at the 4-cell stage (day 2) of mouse embryos,
      followed by further development in a pure culture medium until fixation on days
      3, 4 and 5. In staurosporin-induced embryos, light microscopy immunostaining of
      nucleolar proteins (fibrillarin, Nopp140, protein B23) did not reveal changes in
      nucleolar morphology on day 3. On days 4 and 5, more compact (roundish) nucleoli
      (in comparison with controls) were observed. The embryos treated with
      camptothecin displayed a similar staining pattern to those with staurosporin at
      each day. In actinomycin-D-treated embryos, marked changes in nucleolar
      appearance were visible as early as day 3. These changes in nucleolar morphology
      consisted of loss of the reticulation appearance and fragmentation of nucleoli.
      In addition to nucleolar changes, significantly decreased cell proliferation was
      observed. The induced embryos did not reach the blastocyst stage. The number of
      blastomeres was decreased, and staining with Hoechst 33342 revealed a significant
      percentage of apoptotic nuclei (condensed/fragmented nuclei) from day 4.

PMID- 14640193
TI  - Essential metal depletion in an anaerobic reactor.
AB  - The effect of the absence of trace elements on the conversion of a mixture of
      volatile fatty acids by a distillery anaerobic granular sludge was investigated.
      Two UASB reactors were operated under identical operational conditions except for
      the influent trace metal concentrations, during 140 days. Experiments were
      carried out in three periods, where different organic loading rates (OLR) were
      applied to the reactors. The total trace metal concentration steadily decreased
      at a rate of 48 microg metal/g TS.d in the deprived reactor (down to 35% of their
      initial value). In contrast, trace metals accumulated in granules present in the
      control reactor. At the end of the experiment, the COD removal efficiencies were
      99% and 77% for the control and deprived reactors, respectively, due to the lack
      of propionate conversion. Cobalt sorption experiments were carried out in order
      to study its speciation, and its effects on the speciation of other metals as
      well. A paper mill wastewater treating granular sludge was also included in the
      study as a comparison. Results obtained showed that the principal metal forms
      normally associated with any sludge are a function of each soluble metal
      concentration in the system, and the characteristics of the particular sludge.

PMID- 14640194
TI  - Enrichment and immobilization of quinone-respiring bacteria in anaerobic granular
      sludge.
AB  - The capacity of an anaerobic granular sludge for serving as an immobilizing
      mechanism for quinone-respiring bacteria was evaluated. The inoculum was
      continuously fed with a basal medium containing the humic model compound,
      anthraquinone-2,6-disulfonate (AQDS), as a terminal electron acceptor. Complete
      reduction of AQDS was achieved by the granular sludge for a prolonged period in
      an anaerobic bioreactor provided with a mixture of volatile fatty acids as a
      substrate. Phylogenetic analysis revealed the enrichment and immobilization of
      AQDS-respiring bacteria appearing as dominant organisms in the microbial
      population of the AQDS-supplemented reactor, compared to a reactor control
      operated under methanogenic conditions. The consistent quinone-reducing capacity
      observed in the consortium indicates that it is feasible to apply quinone
      reducing microorganisms in continuous bioreactors and this ability can
      potentially be important in wastewaters rich in humic substances. The quinone
      reducing activity could also be applied to accelerate the conversion of
      xenobiotics susceptible to reductive biotransformations such as azo dyes and
      polychlorinated compounds in continuous bioreactors.

PMID- 14640195
TI  - Influence of the initial substrate to microorganisms concentration ratio on the
      methanogenic inhibition test.
AB  - The influence of the initial substrate to microorganisms ratio (So/Xo) on the
      inhibition of the methane production caused by 4-chlorophenol, 4CP, was studied.
      The effect of the 4CP on glucose degradation was evaluated measuring the quantity
      of methane produced during the test. One part of the inoculum was used as it came
      from its origin and another was fed with ethanol in order to maintain its
      activity. The inhibition tests were carried out using the same initial
      concentration of glucose, three initial suspended solids concentrations and eight
      initial concentrations of 4CP. The use of ethanol-acclimatized sludge presented a
      great influence on the inhibition results, since the inhibition was greater in
      the raw sludge than the acclimated one. Significant differences in the inhibition
      tests were found depending on the initial So/Xo ratio with respect to the glucose
      as substrate. It was observed that the inhibition decreases as the So/Xo
      decreases, in other words as the initial biomass concentration increases. When
      the results were analyzed in respect to the 4CP it was observed that the
      inhibition increases as the So/Xo increases. Also, it was observed that for the
      same value of So/Xo there is an increase of the inhibition when the quantity of
      Xo decreases.

PMID- 14640196
TI  - Influence of multiple substrates on anaerobic protein degradation in a packed-bed
      bioreactor.
AB  - Data on the influence of substrate composition on the anaerobic degradation of
      bovine serum albumin (BSA) in a bench-scale packed-bed reactor are presented and
      discussed from the standpoint of substrate consumption kinetics. The experiments
      were carried out in a horizontal-flow anaerobic immobilized biomass (HAIB)
      reactor fed with BSA based substrates. BSA was the sole carbon source in the
      first one, while the others were composed of BSA, carbohydrates and lipids. In
      all the experiments, the HAIB reactor was operated at the hydraulic detention
      time of 4 hours. The reactor's performance was evaluated based on physicochemical
      and chromatographic analyses and also on microscopy techniques. A kinetic model
      of irreversible first-order series-parallel reactions with two intermediate
      products was proposed, allowing evaluation of the microbial consortium's affinity
      with the substrates and the metabolic compounds formed. As the first-order
      kinetic model adhered quite well to the experimental data, the initial protein
      degradation rates (k) were estimated. The presence of carbohydrates and lipids
      led the initial protein degradation rate to be reduced. However, the system fed
      with protein and carbohydrates showed higher process stability.

PMID- 14640197
TI  - Accumulation of long chain fatty acids onto anaerobic sludge under steady state
      and shock loading conditions: effect on acetogenic and methanogenic activity.
AB  - Accumulation of substrate onto the biomass was quantified under steady-state and
      shock conditions in a fixed bed reactor fed with an oleic acid-based synthetic
      effluent. The accumulation of substrate onto the sludge was more dependent on
      oleic acid concentration than on oleic acid loading rate and decreased the
      acetogenic, acetoclastic and hydrogenophilic activity. However, even when the
      methanogenic activity measurements indicate a severe inhibition, the anaerobic
      sludge was able to methanise efficiently the accumulated substrate that was
      mainly adsorbed LCFA. Methanogenic activity measurements for a sludge loaded with
      2,861 mg COD/gVSS as LCFA, revealed that only hydrogenophilic activity was
      detected, whereas the methanogenic activities with acetate, propionate and
      butyrate as substrates were null. However the methanogenic activity of the same
      sludge after allowing the depletion of the adsorbed LCFA were significantly
      enhanced in the presence of all substrates, except in propionate. A discussion
      about the relative importance of metabolic inhibition and transport limitations
      for the anaerobic degradation of LCFA is launched.

PMID- 14640198
TI  - Dynamics of extracellular polymeric substances in UASB and EGSB reactors treating
      medium and low concentrated wastewaters.
AB  - In this work the dynamic study of EPS (Extracellular Polymeric Substances)
      concentration and distribution during the operation of two different reactor
      configurations (UASB and EGSB) is presented, treating medium (5 g COD/l) and low
      concentrated (0.5 g COD/l) wastewater. Medium-concentrated wastewater was
      supplied for granules maturation as well as for stabilisation of the process. The
      effect of substrate change on granule characteristics was followed in both
      reactors. Total concentration of EPS associated to steady operation, was higher
      in the UASB reactor. The change to a low-concentrated substrate led to an
      increased difference, promoting a sharp destabilisation of the EGSB reactor,
      observing an increment in filamentous structures, causing biomass flotation and
      wash out. Although total concentration of EPS remained almost constant in the
      UASB reactor, their composition and distribution presented significant
      differences. The ratio of protein/polysaccharides as well as acidic
      polysaccharides/total (neutral + acidic) polysaccharides decreased drastically in
      the EGSB reactor, while in the UASB reactor, the decrease was not so important
      and not enough for destabilisation of granule structure. Moreover,
      polysaccharides distribution seemed to have an important role in granule
      stability being enough to maintain granule cohesion only in the case of the UASB
      reactor. These observations point to composition and distribution of EPS rather
      than their total concentration as key parameters for granule stability and
      settleability.

PMID- 14640199
TI  - Improvement of the properties of granular sludge in UASB reactors by flow
      pulsation.
AB  - The objective of this work is to improve the characteristics of granular sludge
      by modification of the hydraulics of the bed through flow pulsation. Three UASB
      reactors, two operated with pulsing flow (P1 and P2) and a third without
      pulsation (NP), were started-up. Both recycling and feeding flow were pulsed in
      the reactor P1, while in reactor P2, only the feeding was pulsed. A high increase
      in the removal capacity and stability were achieved by applying pulsation in
      reactors P1 and P2 when compared to the non-pulsed one. Besides, pulsation
      promotes the formation of particles of smaller size and higher porosity, thus
      increasing the specific surface of the bed and consequently, the specific
      activity. In fact, while reactors P1 and P2 had a 95% COD removal when working at
      high organic loading rates (12 kg COD/m3 x d), reactor NP only reached 6 kg
      COD/m3 x d with 85% of removal capacity.

PMID- 14640200
TI  - Molecular ecology of anaerobic granular sludge grown at different conditions.
AB  - Qualitative and quantitative diversity of microorganisms present in anaerobic
      granular sludges fed with different substrates, as well as the structure of these
      granules have been studied using fluorescent 16S rRNA-targeted in situ
      hybridization and electron microscopy. The granules showed a multi-layered
      structure, in which both densely packed and loose micro-colonies, channels and
      holes could be observed. Only bacteria were found in the outer shell of the
      granules, while both archaea and bacteria were detected in the inner core.
      Although high cell density was found in the granules (more than 10(11)
      cells/gram, determined by DAPI-stain) only a low percentage of cells was able to
      hybridize with the rRNA-targeted probes. Significant quantitative and qualitative
      differences were observed in the composition of granules fed with different
      substrates (formate, acetate at high and low concentrations, propionate, sucrose,
      starch and peptone). Bacterial cells were mostly gram-positives. Active
      proteobacteria were scarce in the granules exposed to VFA. Syntrophobacteria
      became dominant in the propionate-grown biomass. Concerning methanogenic archaea,
      Methanosaeta was the predominant species using complex substrates or low acetate
      concentration fed granules, while Methanosarcina and members of
      Methanobacteriales were predominant in the granules grown at high concentration
      of acetate or formate, respectively. Other Methanomicrobiales and
      Methanococcales, have been detected in the anaerobic granular sludge in the
      conditions used in this work.

PMID- 14640201
TI  - Microbial community evaluation of anaerobic granular sludge from a hybrid reactor
      treating pentachlorophenol by using fluorescence in situ hybridization.
AB  - We used in situ hybridization with fluorescently labeled rRNA-targeted
      oligonucleotide probes concurrently with microscopic examinations and methane
      measurements to characterize the microbial community of an anaerobic hybrid
      reactor treating pentachlorophenol (PCP) with a mixture of fatty acids
      (propionic, butyric, acetic and lactic) and methanol. Archaeal cells detected
      with probe ARC915 prevailed in anaerobic granular sludge without and with the
      addition of PCP in a range of 2.0 to 21.0 mg/L to the reactor. This group
      accounted for 81 and 90% of the DAPI-stained cells before and after the addition
      of 21 mg/L of PCP, respectively. In these conditions, cells detected with the
      Methanosarcinales specific probe (MSMX860) were the only methanogenic Archaea
      found and accounted for 59 to 87.6% of the DAPI-stained cells. No cells were
      detected by the Methanomicrobiales (MG1200), Methanobacteriaceae (MB1174) and
      Methanococcaceae (MC1109) specific probes. Bacterial cells detected with probe
      EUB338 were found in very low numbers, which ranged from 5.7 to 1.0% of the DAPI
      stained cells. This finding agrees with the scanning electron microscope
      examinations, in which cells morphologically resembling Methanosaeta and
      Methanosarcina were predominantly observed in the granular sludge. Results
      contributed to the investigation of the importance of the methanogens during PCP
      degradation.

PMID- 14640202
TI  - Evolution of the bacterial community during granules formation in denitrifying
      reactors followed by molecular, culture-independent techniques.
AB  - The microbial community in two acetate-fed denitrifying reactors, inoculated with
      methanogenic sludge, was monitored by 16S rDNA-based methods (SSCP and FISH).
      Both reactors converged to similar, stable communities. The predominant organisms
      belonged to the genera Thauera, Paracoccus and Denitrobacter, detected both by
      molecular and culture-based methods.

PMID- 14640203
TI  - Acclimation of mesophilic anaerobic sludge to thermophilic conditions: PCR genera
      detection methodology.
AB  - In Mexico, sludge from wastewater treatment plants is a public health problem,
      especially for the infant population due to the presence of pathogens and
      parasite eggs. Therefore, it is of great interest to apply proper treatment
      methods for those wastes. An option proposed for the removal of possible
      infectious sources is thermophilic anaerobic digestion, even though a limitation
      for its acceptance is the slow start-up of the reactors. The transformation of a
      mesophilic anaerobic sludge for its utilization as a thermophilic inoculum, by
      means of direct temperature increase up to 55 degrees C and feeding of the
      inoculum with synthetic medium was possible in two months. As a main part of the
      work and with the objective of evaluating the changes in the methanogenic
      microbial population during the sludge treatment, a specific detection technique
      for these bacteria has been developed and validated, based on the use of the
      polymerase chain reaction (PCR).

PMID- 14640204
TI  - Robust regulation of anaerobic digestion processes.
AB  - This paper deals with the problem of controlling anaerobic digestion processes. A
      two-step (i.e. acidogenesis-methanization) mass balance model is considered for a
      1 m3 fixed bed digester treating industrial wine distillery wastewater. The
      control law aims at regulating the organic pollution level while avoiding washout
      of biomass. To this end, a simple output feedback controller is considered which
      regulates a variable strongly related to the Chemical Oxygen Demand (COD).
      Numerical simulations assuming noisy measurements first illustrate the robustness
      of this control procedure. Then, the regulating procedure is implemented on the
      considered anaerobic digestion process in order to validate and demonstrate its
      efficiency in real life experiments.

PMID- 14640205
TI  - Bicarbonate dosing: a tool to performance recovery of a thermophilic methanol-fed
      UASB reactor.
AB  - The thermophilic-anaerobic treatment of methanol-containing wastewater in an
      upflow anaerobic sludge blanket (UASB) reactor, was found to be quite sensitive
      to pH shocks, both acid and alkaline. The results of the recovery experiments of
      sludge exposed to an alkaline shock, indicated that the addition or deprivation
      of sodium bicarbonate (NaHCO3) in the medium, plays an important role in the
      competition of methanogens and (homo)acetogens for methanol. In addition, caution
      has to be taken when using NaHCO3 for buffering methanol-containing wastewaters,
      since its introduction in the system will favour (homo)acetogenesis when proper
      conditions are not established. Based on these results, a recovery strategy for
      methanogenesis was proposed where bicarbonate is supplied stepwise, and the
      reactor is operated in a batch mode. This strategy was found to be appropriate,
      i.e. the results revealed that the recovery of methanogenesis on methanol from a
      reactor upset or complete failure caused by pH shock is possible, even in systems
      where (homo)acetogens are outcompeting methanogens. The time and the number of
      feedings required will depend on the degree of deterioration of the sludge.

PMID- 14640206
TI  - Automatic control of volatile fatty acids in anaerobic digestion using a fuzzy
      logic based approach.
AB  - A control law based on fuzzy logic was developed and validated for an anaerobic
      wastewater treatment process. The controlled variable was the concentration of
      volatile fatty acids (VFA) in the reactor and the manipulated variable was the
      input flow rate. In order to use it as the input of the fuzzy sets, the
      controlled variable was treated using an algorithm of interpolation,
      extrapolation and filtering. The treatment of VFA values attempted to anticipate
      the behaviour of the variable and to avoid the inherent delay of the response,
      associated to the time constant of the system. Furthermore, the controlled
      variable derivative was used as a second input of the fuzzy sets to increase or
      decrease the speed of the control action. The control law was applied to a 0.948
      m3 fixed-bed anaerobic reactor treating raw and diluted (1:2) industrial
      distillery vinasses. The validation was performed establishing different
      transient states between different set points in the range of 0.8 and 1.8 g VFA/l
      and different concentrations of the influent. The control law proved to be
      reliable supplying an adequate control action in terms of amplitude and velocity
      to achieve the desired set point for different types of perturbation and control
      purposes.

PMID- 14640207
TI  - Factors affecting constancy of acetate concentration and correct determination of
      methanogenic activity in pH-stat experiments.
AB  - The determination of methanogenic activity with a pH-stat titration bioassay is
      evaluated utilising a mathematical model of this system. For given kinetic
      parameters and experimental conditions the model calculates the development of
      titrant flow and acetate concentration during experiments. Simulations of
      experiments under various conditions are compared. They show that the original
      method inherently causes a strong drift of acetate concentration during the
      experiments and a misestimation of methanogenic activity. As a solution to these
      disadvantages the addition of sodium hydroxide to the titrant and a careful
      control of pH during flushing the reactor with gas prior to the experiment are
      recommended. In this way a better constancy of acetate concentration and a more
      accurate determination of methanogenic activity should be achievable. The
      accuracy of this method is limited by the stability of pH-electrode calibration
      parameters.

PMID- 14640208
TI  - The effect of the supplementation with a primary carbon source on the resistance
      to oxygen exposure of methanogenic sludge.
AB  - Anaerobic methanogenic consortia have a considerable resistance to oxygen
      exposure. Yet, most research has been focused on the study of the tolerance to
      oxygen of anaerobic immobilized biomass. Less is known on the potential of the
      anaerobic suspended biomass for withstanding exposure to oxygen and the effect of
      a primary degradable substrate on such resistance. Thus, the objective of this
      work was to determine the effect of the amount of a primary degradable substrate
      (sucrose) on the resistance of a methanogenic suspended biomass to oxygen
      exposure. It was found that the inhibition of disperse anaerobic sludge by oxygen
      exposure decreases when the concentration of the supplemented carbon source
      increases. This is in agreement with the fact that aerobic respiration of the
      added substrate by the facultative heterotrophic bacteria, always present in this
      type of sludge, has been found in previous studies as one of the main mechanisms
      protecting methanogens against O2. From a practical point of view, this suggests
      that aeration of anaerobic systems should be possible without inhibiting the
      activity of methanogenic bacteria if an adequate ratio between oxygen and COD
      feeding is maintained. Such a ratio will depend however on the wastewater initial
      COD concentration.

PMID- 14640209
TI  - Anaerobic biodegradation of BTEX using Mn(IV) and Fe(III) as alternative electron
      acceptors.
AB  - Anaerobic BTEX biodegradation was tested in batch experiments using an anaerobic
      sediment as inoculum under Fe(III) and Mn(IV) reducing conditions. All BTEX were
      degraded under the conditions tested, specially under Mn(IV) reducing conditions,
      where benzene was degraded at a rate of 0.8 micromol l(-1) d(-1), significantly
      much faster than Fe(III) reducing conditions. Under Fe(III) reducing conditions,
      ethylbenzene was the compound that degraded at the faster rate of 0.19 micromol
      l(-1) d(-1). Mn(IV) reducing conditions are energetically more favourable than
      Fe(III), therefore, BTEX were more rapidly degraded under Mn(IV) reducing
      conditions. These results represent the first report of the degradation of
      benzene with Mn(IV) as the final electron acceptor. Amorphous manganese oxide is
      a natural widely distributed metal in groundwater, where it can be
      microbiologically reduced, leading to the degradation of monoaromatic compounds.

PMID- 14640210
TI  - Modeling of the Acid Orange 7 anaerobic biodegradation.
AB  - It was found that 1-amino-2-naphthol, an intermediate generated during the
      anaerobic degradation of Acid Orange 7, is a redox mediator which plays a
      significant role in the transport of electrons to the dye, thus giving to the
      whole process an autocatalytic nature. Evidences of the autocatalytic behaviour
      were observed in experimental data previously obtained under batch and fed-batch
      conditions. In this paper, a kinetic model considering all these factors is
      proposed and validated. In batch assays, this model agrees satisfactorily with
      the experimental data. In the case of fed-batch assays, the autocatalytic model
      only can be applied satisfactorily after the first feeding, since the degradation
      of Acid Orange 7 after the second and third feedings followed a first-order
      kinetic. This fact can be explained due to the presence of the redox mediator
      previously generated during the reactions that took place after the first
      feeding.

PMID- 14640211
TI  - Anaerobic degradation kinetics of a cholesteryl ester.
AB  - The most important components of wool scouring effluent grease are esters of
      sterols. Cholesteryl palmitate (CP) is the main ester in this grease. In this
      paper, the influence of the ester concentration in the anaerobic digestion and
      the relative rate of the different degradation steps, are studied. The experiment
      was carried out to measure methane production in the anaerobic degradation of
      acetate, palmitic acid (PA) and CP. A first-order kinetic model was assumed for
      hydrolysis and Monod models were assumed for both the methanogenic and acetogenic
      steps. Maximum hydrolysis rate was found to be around 20 times faster than the
      maximum methanogenic reaction rate during the experience. The lanolin emulsion
      drop size effect was also evaluated employing fine and coarse stock lanolin
      emulsions and no adapted sludge. Concentrations of 13.7 to 4.6 gCOD x l(-1) were
      employed. In a previous study, the effect of palmitic acid emulsion size was
      found important when similar sludge was tested. When esters are degraded, a
      significant effect of drop size on the degradation rate was not found. The
      difference between CP and PA emulsions behavior could be due to the fact that
      cholesterol produced during the ester degradation has a protective effect on the
      sludge.

PMID- 14640212
TI  - Influence of feedstock and bleaching technologies on methanogenic toxicity of
      kraft mill wastewater.
AB  - Chlorine-bleached effluent is problematic for anaerobic wastewater treatment due
      to its high toxicity against methanogenic bacteria. To date, alternative
      bleaching processes are being introduced, such as elemental chlorine-free (ECF)
      and total chlorine-free (TCF). The purpose of this study was to investigate the
      influence of bleaching technologies and different types of feedstock on
      methanogenic activity. In order to compare the toxicity of the different
      bleaching sequences per unit of COD, the 50%-inhibitory concentration (50% IC)
      for methanogenic bacteria of the different bleaching effluents were compared. The
      results show that there is no direct relationship between the effluent's
      methanogenic toxicity and the bleaching sequences. Methanogenic toxicity ranged
      from 0.6 to 2.4 g COD/L.

PMID- 14640213
TI  - Anaerobic treatment of natural tannin extracts in UASB reactors.
AB  - Tannin extracts are substances commonly used in leather production processes.
      Since most of the steps of tannery manufacturing processes are carried out in
      aqueous environments, the presence of these compounds in the wastewaters is
      important. The aim of this work is to study the feasibility of the anaerobic
      degradation of three natural tannin extracts in three Upflow Anaerobic Sludge
      Blanket (UASB) reactors, which were fed with increasing concentrations of two
      condensed (quebracho and wattle) and one hydrolysable tannin extract (chestnut).
      Concentrations of applied extracts were 100, 200, 400, 800 and 1,000 mg/l, and 5
      g/l of glucose was used as cosubstrate. Reactors were operated during 210 days
      and their performance was evaluated from the values of total and soluble COD,
      total and intermediate alkalinity, volatile fatty acids, pH and UV absorption at
      280 nm. COD removal efficiencies higher than 85% were achieved in all cases.
      However, tannin extract removal efficiencies (based on UV-280 nm absorption
      measurements) were significantly lower, around 20% for condensed extracts and 60%
      for the hydrolysable one, when the reactors operated with the highest tannin
      extract concentration. The operation of the reactors was stable, commonly with
      alkalinity ratios below 0.30. Mass balances carried out indicate that most of the
      COD removal efficiencies are due to the removal of the readily biodegradable
      organic matter (glucose), whereas the tannin extracts are hardly anaerobically
      biodegradable, especially condensed extracts (wattle and quebracho).

PMID- 14640214
TI  - Biodegradation of octylphenol polyethoxylates by denitrification.
AB  - The biodegradation route of the octylphenol ethoxylates (OPEOs) by
      denitrification in an upflow anoxic sludge blanket (UASB) reactor was studied. An
      anaerobic sludge adapted to denitrifying conditions with acetate was adapted with
      increasing amounts of OPEOs and diminishing amounts of acetate until only 300 mg
      x L(-1) of OPEOs were fed. Only 70% of stoichiometric NO3- was fed so partial
      removal was expected. The total OPEOs fed was transformed with 70% COD removal.
      HPLC and GC-MS analyses showed that octylphenol (OP) was immediately formed but
      disappeared while other intermediates, the ethoxylated moieties; mono and
      diethoxylate (OPEO1 and OPEO2 respectively) led to the cleavage of the alkyl
      chain to form propylphenol triethoxylate (PPEO3) and heptylphenol diethoxylated
      (HPEO2). These last two compounds are produced due to an attack to both sides of
      the molecule; the hydrophilic and the hydrophobic. These findings suggest three
      simultaneous routes of OPEO degradation.

PMID- 14640215
TI  - Simultaneous biodegradation of a phenol and 3,4-dimethylphenol mixture under
      denitrifying conditions.
AB  - Denitrification is a feasible alternative for the treatment of phenolic bearing
      wastewaters. The aim of this study was to evaluate the biodegradability of
      phenolic compounds, as the only carbon and energy source in batch and continuous
      experiments, using nitrate as a final electron acceptor. Experiments in a
      continuous upward anaerobic sludge bed reactor demonstrated the possibility of
      biodegrading a mixture of phenol and 3,4-dimethylphenol at organic loads of 251.6
      and 39.5 mg/L-d, respectively, at a COD/NO3(-)-N ratio of 2.57. A nitrogen
      production efficiency of 86% was obtained according to the nitrate consumption.
      GC-MS analyses demonstrated that m-cresol was an intermediate of 3,4
      dimethylphenol degradation in batch conditions, and had an inhibitory effect on
      phenol degradation.

PMID- 14640216
TI  - Operating feasibility of anaerobic whey treatment in a stirred sequencing batch
      reactor containing immobilized biomass.
AB  - The scope of this work was to evaluate the operating feasibility of anaerobic
      whey treatment in a stirred sequencing batch reactor (ASBR) containing biomass
      immobilized on inert support. Assays were performed using 8-hour cycles and
      agitation rate of 200 rpm at 30 +/- 1 degrees C, for treating cheese whey
      containing 500 to 4,000 mgCOD/L, which corresponded to a volumetric organic load
      (VOL) of 0.81 to 5.7 gCOD/L x d. Stability and high organic matter removal of
      about 96% were achieved at effluent concentration below 160 mgCOD/L for non
      filtered samples. Operating stability of the reactor was shown to be strongly
      dependent on the alkalinity supplementing strategy during the assay, especially
      during the startup period, where NaHCO3 supplementation was approximately 20-30%
      of the chemical oxygen demand (mgNaHCO3/mgCOD). After startup, alkalinity
      supplementation could be reduced down to 10% maintaining efficiency and
      stability. Moreover, proper homogenization of the system through mechanical
      agitation was also shown to be indispensable, especially with increasing organic
      load.

PMID- 14640217
TI  - Riboflavin as a redox mediator accelerating the reduction of the azo dye mordant
      yellow 10 by anaerobic granular sludge.
AB  - Azo dyes are important persistent pollutants of textile industry effluents.
      Reduction of these dyes to their corresponding aromatic amines under anaerobic
      conditions can be used to initiate biodegradation. Since electron transfer is
      suggested to be rate limiting, redox mediators are being considered to improve
      dye reduction kinetics. This study evaluates the use of riboflavin, the redox
      active moiety of common occurring enzyme cofactors, as a redox mediator to
      accelerate the reduction of the azo dye, mordant yellow 10 (MY10). Dye reduction
      was found to follow zero order kinetics, the total rate constant (Vtotal) could
      be separated into two components: the rate of reduction due to direct contact
      between enzymes in the sludge with the dye (Vdirect); and the rate of reduction
      mediated by riboflavin (Vmediated). Riboflavin increased the Vtotal by 61% at
      extremely sub-stoichiometric concentrations of 9.1 micromol l(-1), which
      corresponded to a molar riboflavin:dye ratio of 1:60. The accelerating effect of
      riboflavin displayed saturation kinetics at higher concentrations, with a maximum
      increase of Vtotal of approximately 2-fold. A model is presented which assumes
      that Vmediated depends on the activity of riboflavin reductase (RR) and thus
      follows Michaelis-Menton kinetics with respect to the riboflavin concentration.
      The half-velocity constant (Km) was very low (6.3 micromol l(-1)), indicating a
      high affinity of the sludge RR for riboflavin. Both Vdirect and Vmediated were
      found to be proportional to the assay sludge concentration. The results taken as
      a whole indicate that vitamin levels of riboflavin can be utilized to improve the
      kinetics of azo dye reduction during anaerobic treatment.

PMID- 14640218
TI  - Assessment of compatible solutes to overcome salinity stress in thermophilic (55
      degrees C) methanol-fed sulfate reducing granular sludges.
AB  - High NaCl concentrations (25 g x L(-1)) considerably decreased the methanol
      depletion rates for sludges harvested from two lab-scale sulfate reducing UASB
      reactors. In addition, 25 gNaCl x L(-1) strongly affected the fate of methanol
      degradation, with clear increase in the acetate production at the expense of
      sulfide and methane production. The addition of different osmoprotectants, viz.
      glutamate, betaine, ectoine, choline, a mixture of compatible solutes and K+ and
      Mg2+, slightly increased methanol depletion rates for UASB reactors sludges.
      However, the acceleration in the methanol uptake rate favored the homoacetogenic
      bacteria, as the methanol breakdown was steered to the formation of acetate
      without increasing sulfate reduction and methane production rates. Thus, the
      compatible solutes used in this work were not effective as osmoprotectants to
      alleviate the acute NaCl toxicity on sulfate reducing granular sludges developed
      in methanol degrading thermophilic (55 degrees C) UASB reactors.

PMID- 14640219
TI  - Sequential anaerobic/aerobic biotreatment of bark leachate.
AB  - Bark leachate is generated from sawmill operations such as log storage sites and
      contains polymeric tannins, carbohydrates, organic acids, phenolic and resin
      compounds. The present study was aimed at assessing the performance of a
      sequential anaerobic and aerobic treatment, for both chemical oxygen demand (COD)
      and phenol removal, under various combinations of operational conditions, in the
      continuous mode. After anaerobic treatment in a five litres upflow anaerobic
      sludge bed (UASB) reactor, the leachate was directed into two parallel aerobic
      reactors, either an activated sludge unit or a fixed film submerged filter
      (packed with polyethylene Flexirings), both of a volume of one litre and
      oxygenated by air diffusion. For a leachate of 22 gCOD/l, an overall COD removal
      of 96-98% was achieved at an hydraulic residence time (HRT) of 4 days for the
      anaerobic reactor and one day for either aerobic systems. The phenol
      concentration generally increased after anaerobic treatment but was below the
      detection limit (50 ppb) after aerobic polishing. Radiorespirometric microcosms
      with 14C-labelled phenol confirmed that phenol was mineralized in the aerobic
      reactors. The performances of both aerobic systems were similar for COD and
      phenol removal. Thus, a sequential anaerobic/aerobic treatment was able to
      effectively address the contamination of a bark leachate discharge, including
      phenols.

PMID- 14640220
TI  - Impact of temperature on performance, microbiological, and hydrodynamic aspects
      of UASB reactors treating municipal wastewater.
AB  - The present study examined the feasibility of treating municipal wastewater by a
      UASB system under low-temperature conditions. Two reactors were started-up at 20
      degrees C and subsequently operated at temperatures of 32, 20, 15, 11, and 6
      degrees C applying several hydraulic retention times (HRTs) ranging from 48 to 3
      h during an operational period of approximately 900 days. Chemical oxygen demand
      (COD) removal efficiency ranged from 70 to 90% up to an HRT of 6 h and 11 degrees
      C. The performance of the reactor was not very satisfactory during 6 degrees C
      operation (average COD removal 40%). Sulfate reduction played an important role
      in COD reduction. Digital image analysis and scanning electron microscopic
      observations of sludge samples revealed aggregation of biomass in the form of
      irregular shaped granules (mean size ranged from 1.5 to 3.0 mm). The hydraulic
      regime in the reactor was impacted by the change in operating temperature. This
      study demonstrated that the UASB system could be applied successfully for pre
      treatment/treatment of municipal wastewater under low-temperature conditions.

PMID- 14640221
TI  - Decentralised treatment of concentrated sewage at low temperature in a two-step
      anaerobic system: two upflow-hybrid septic tanks.
AB  - The decentralised treatment of concentrated sewage (about 3,600 mgCOD/l) at low
      temperature was investigated in a two-step anaerobic system: two-anaerobic hybrid
      (AH) septic tanks (each 0.575 m3). The two reactors were placed in a temperature
      controlled-room and the HRT was 2.5 days for each reactor. The system was fed
      with concentrated domestic sewage, mainly black water from about 40 toilets
      flushed with only 4 litre of water and a limited amount of grey water. The system
      showed high removal efficiency for the different COD fractions. Mean removal
      efficiencies in the two-step AH-septic tank at 5 days HRT and 13 degrees C were
      94, 98, 74 and 78% for total COD, suspended COD, colloidal COD and dissolved COD
      respectively. The results of short run experiments indicated that the presence of
      reticulated polyurethane foam (RPF) media in the AH-septic tank improved the
      removal of suspended COD by 22%. The first AH-septic tank was full of sludge
      after 4 months of operation due to the high removal of particulate COD and the
      limited hydrolysis at low temperature conditions. Therefore, a simple
      mathematical model was developed based on ADM1 (the IWA model in 2002). Based on
      the experimental results and the mathematical model, only a one-step AH septic
      tank is required. An HRT of 5.5-7.5 days is needed for that one-step AH septic
      tank to treat concentrated sewage at a low temperature of 13 degrees C. Such a
      system can provide a total COD removal as high as 87% and will be full of sludge
      after a period of more than a year.

PMID- 14640222
TI  - Performance evaluation of an UASB reactor used for combined treatment of domestic
      sewage and excess aerobic sludge from a trickling filter.
AB  - This work aimed at evaluating the influence of the excess sludge produced in a
      trickling filter (TF) on the performance of a UASB reactor used for the combined
      treatment of domestic sewage and aerobic sludge. During phase 1 of the research,
      the UASB reactor/TF system was fed with domestic sewage pumped directly from the
      sewer collector of Arrudas stream, in Belo Horizonte-Brazil. During phase 2,
      besides feeding the reactor with domestic sewage, the UASB reactor was also fed
      with the aerobic sludge from the trickling filter. The UASB reactor, with a
      volume of 420 litres, was operated at a mean hydraulic detention time of 5.6
      hours in both operational phases. After 133 days of continuous monitoring, no
      detrimental effect was noticed on the performance of the UASB reactor regarding
      the return of the aerobic sludge produced in the TF. On the contrary, the COD
      results indicated a higher percentage of compliance with the discharge standards
      set forth by the Brazilian environmental legislation. During phase 2 of the
      research, when the UASB reactor was used for combined treatment of domestic
      sewage and excess aerobic sludge from the TF, the anaerobic effluent presented
      mean concentrations of 108 mgCOD x L(-1), 57 mgBOD x L(-1) and 18 mgTSS x L(-1).

PMID- 14640223
TI  - Effect of aluminium and sulphate on anaerobic digestion of sludge from wastewater
      enhanced primary treatment.
AB  - The combined and individual effects of aluminium and sulphate at concentrations
      of 1,000 mg/l as Al(OH)3, and 150 mgSO4(2-)/L as K2SO4, respectively, on the
      anaerobic digestion of sludge from enhanced primary treatment (EPT) were
      evaluated in 1 L capacity semi continuous reactors. It was found that at 59 days,
      aluminium inhibits the specific methanogenic activity (SMA) of methanogenic and
      acetogenic bacteria resulting in a 50% to 72% decrease. Sulphate also inhibits
      (48% to 65%) the SMA of the same type of bacteria. Methanogenic and acetogenic
      bacteria were able to adapt, to a different extent, to the assayed concentrations
      of aluminium and sulphate. However, the combination of aluminium and sulphate
      resulted in a higher inhibition, especially of the hydrogenophilic methanogenic
      bacteria. Indeed, this effect remained during the time of the experiment,
      maintaining an inhibition of 44% at 114 days. Feeding with EPT sludge led to a
      bigger decrease in SMA of each bacterial group, with respect to the other
      treatments with time. It is concluded that the acidification of anaerobic
      reactors fed with EPT sludge is due, among other causes, to the concurrent
      presence of aluminium and sulphate.

PMID- 14640224
TI  - Evaluation of the start-up of an integrated municipal solid waste and leachate
      treatment system.
AB  - A pilot-scale experiment was set up in the laboratory with the purpose of
      investigating the most relevant aspects of the anaerobic digestion of municipal
      solid wastes (MSW), which are necessary for the preparation of future feasibility
      studies and cost-benefit analyses. The experiment consisted of a comparative
      analysis among three different lines of operation, each one consisting of three
      anaerobic MSW reactors (with unit volume of 700 L): conventional landfill (line
      1), raw leachate recycling (line 2), and integrated treatment, with seeded
      leachate recycling (line 3). So, a UASB reactor was installed in the integrated
      treatment line with the purpose of removing the organic load of the leachate of
      the MSW reactors and utilising the biological sludge produced for inoculation of
      the waste digestion. The endogenous inoculation promoted in line 3, by means of
      recirculation of the leachate and return of the exceeding biological sludge
      produced in the UASB reactor, has favoured the initial fermentation stage and
      also the acceleration of the methanogenic phase.

PMID- 14640225
TI  - The influence of pH in the hydrolytic stage of anaerobic digestion of the organic
      fraction of urban solid waste.
AB  - The influence of the pH in the first stage, the hydrolytic stage, of the
      anaerobic digestion of the organic fraction of urban solid waste in a two phase
      anaerobic reactor was studied. The reactor was fed with a solution of the organic
      fraction of urban solid residues containing 5 to 7% solids. Four reactors with a
      working volume of 3 L were used, the experiments were done at three controlled
      pHs; 6, 7, and 8, and one with free pH, the temperature was keep at 37 degrees C
      in all the experiments. The higher degradation of TSS and VSS was obtained in the
      reactors operated at pH 7 and 8; 75% degradation of TSS and 85% degradation of
      VSS. The volatile fatty acids were determined at the different pH conditions, no
      significant differences were found, and as was expected, the acetic acid was
      found at the higher value among them (from 25 to 29 g/L). According to the
      results obtained it is possible to conclude that in the case of the hydrolytic
      stage of the anaerobic digestion of the organic fraction of urban solid waste it
      is not necessary to control the pH, the pH is kept stable by the buffer effect of
      the protein residues and other macromolecules present in the residue.

PMID- 14640226
TI  - Liquefaction and methanization of solid and liquid coffee wastes by two phase
      anaerobic digestion process.
AB  - This study attempted to investigate the feasibility of volatile fatty acid (VFA)
      production from coffee pulp hydrolyse, and further to determine the potential of
      methanization of both the pre-acidified effluent and the coffee wastewater. The
      experiments were carried out in 2 completely mixed reactors, each one with a
      working volume of 4 litres. Coffee pulp was used as substrate in the acidogenic
      reactor and different mixtures of pulper and wash-water and pre-acidified
      effluent in the methanogenic one. The acidogenic and methanogenic reactors were
      operated at an organic loading rate of 5 COD g x l(-1) x d(-1) and 0.5 COD g x l(
      1) x d(-1). The total, soluble and VFA's effluent COD concentrations of the
      acidogenic reactor present average values of 57.75, 17.00 and 13.92 g x l(-1)
      respectively. Under these experimental conditions, 23% (COD based) of coffee pulp
      was hydrolysed with a rate of 1.32 gCOD x l(-1) x d(-1) and the soluble fraction
      was transformed to VFA's with an acidification efficiency of 82%. Total VFA's
      concentration reached a value of 13.9 gCOD x l(-1), and acetate, propionate,
      butyrate and valerate represented 52%, 28%, 9% and 11% respectively of the liquid
      phase COD. In the methanogenic reactor, COD removal and methanization of fresh
      coffee wastewater, pre-acidified effluent and both combined occur with an
      efficiency of 85% to 95% respectively, with a characteristic biogas composition
      of 80% CH4 and 20% CO2. These results show that a humid coffee "Beneficio"
      processing daily 23 tons of cherry coffee (fresh fruit), equipped with a two
      stage anaerobic digestion process could generate at least 1,886 CH4 m3 x d(-1).
      This represents an increase in methane production by a factor 3 to 5 compared to
      a "Beneficio" using anaerobic digestion only for the treatment of its wastewater.

PMID- 14640227
TI  - Effect of natural and modified zeolite addition on anaerobic digestion of piggery
      waste.
AB  - The effect of natural and modified zeolites on the anaerobic degradation of
      acetate and methanol was evaluated by the determination of specific methane
      productivity (SMP) in batch minidigesters of 50 mL at doses of 0.01, 0.05 and 0.1
      g of zeolite/g of VSS. The effects of the different zeolite concentrations were
      determined by the results of the SMP. A kinetic characterization with data of
      accumulated methane gas volume was also carried out. In the second phase of the
      study, the effects of natural and nickel zeolite concentrations were tested with
      piggery waste in laboratory scale digesters of 2.5 L operating at semi continuous
      mode, by increasing the organic load applied from 0.2 to 22.0 g TCOD/d
      corresponding to organic loading rates (OLR) of 0.1-8.8 g TCOD/l x d. A greater
      effect of modified zeolite on SMP was observed, with an increase of 8.5 times
      with magnesium zeolite, 4.4 times with cobalt zeolite and 2.8 times with nickel
      zeolite. Two phases were defined in the kinetic study and an increase of more
      than 2 times the apparent constant of digesters with modified zeolites was
      observed in the second phase when compared to unmodified natural zeolite.
      Modified natural zeolite addition to digesters can allow an increase in the
      potential biodegradability of piggery waste solid fraction and/or a considerable
      reduction of digestion volume.

PMID- 14640228
TI  - Anaerobic digestion of manure and mixture of manure with lipids: biogas reactor
      performance and microbial community analysis.
AB  - Anaerobic digestion of cattle manure and a mixture of cattle manure with glycerol
      trioleate (GTO) was studied in lab-scale, continuously stirred tank reactors
      (CSTR) operated at 37 degrees C. The reactor codigesting manure and lipids
      exhibited a significantly higher specific methane yield and a higher removal of
      VS than the reactor treating manure. Microbial population analysis done by
      cultivation--most probable number (MPN) test and specific methanogenic activity
      (SMA) measurement, revealed higher MPN and increased SMA of methanogenic
      populations of biomass from the reactor codigesting manure and lipids. Spatial
      microbial distribution and activity was studied in digested materials
      fractionated into size of particles > 200 microm, 50-200 microm and 0.45-50
      microm. With manure, the main pool of methanogenic activity from propionate,
      butyrate and hydrogen was associated with the particles > 200 microm, while the
      activity of acetotrophic methanogens was uniformly distributed in all fractions.
      When digesting manure and lipids, an enhanced methanogenesis was detected both
      for particles > 200 microm and the 50-200 microm fraction. The molecular methods-
      temperature gradient gel electrophoresis (TGGE), cloning library and sequencing
      of 16S rDNA--showed presence of a restricted number of archaeal species in both
      reactors. The vast majority of clones was phylogenetically most closely related
      to Methanosarcina siciliae.

PMID- 14640229
TI  - Post-treatment of UASB effluent in an expanded granular sludge bed reactor type
      using flocculent sludge.
AB  - The performance of an EGSB (expanded granular sludge bed) reactor type using
      flocculent sludge was evaluated for the post-treatment of effluent from UASB
      reactor treating domestic sewage. A pilot-scale 157.5-L EGSB reactor was
      monitored during a 331-day period. The original concept of the EGSB reactor was
      based on granular sludge use and by applying of high upflow liquid velocities
      (Vup). However, even using flocculent sludge from a UASB full-scale (Mangueira
      Plant, Recife, Brazil), good mixing conditions and high retention of biomass were
      achieved. By applying a 4-h hydraulic retention time and Vup values up to 3.75
      m/h, effluent chemical oxygen demand concentrations in the EGSB were below 87
      mg/L and 55 mg/L, for total and filtered samples, respectively. Total suspended
      solid (TSS) concentrations in the effluent were below 32 mg/L. Good performance
      and stable reactor operation during the whole experimental period were observed.
      Therefore, the EGSB reactor type using flocculent sludge can also be used for
      post-treatment of very dilute anaerobic effluent from reactors treating domestic
      sewage.

PMID- 14640230
TI  - Influence of flocculation conditions in the performance of an experimental
      domestic sewage treatment plant consisting of an anaerobic expanded bed reactor
      followed by dissolved air flotation.
AB  - This paper presents the results of a study performed with an experimental
      domestic sewage treatment plant (240 m3 x d(-1) flow) consisting of expanded bed
      anaerobic reactor (EBAR) followed by dissolved air flotation (DAF) unit. For the
      flotation step, the anaerobic reactor effluent was previously coagulated with 50
      mgFeCl3 x l(-1) and flocculated under different conditions (mean velocity
      gradient, Gf, and flocculation time, Tf). The Gf values were from 60 to 100 s(-1)
      associated with 13 and 20 min Tf values. During the tests, the following
      operational conditions of the flotation unit were maintained: chemical addition
      (50 mgFeCl3 x l(-1)), 18% recirculation rate associated with a pressure of 450 +/
      10 kPa in the saturation chamber and overflow rate of 180 m3 x m(-2) x d(-1).
      Temperature ranged from 23.8 degrees C to 30.0 degrees C. Best results were
      achieved for Gf = 80 s(-1) and Tf = 20 min. For these conditions, the DAF unit
      removal efficiencies were: 94.4% for chemical oxygen demand (with 53 mg x l(-1)
      COD residual), 87% for phosphorus (with 0.80 mgP x l(-1) residual), 96.7% for
      total suspended solids (with 9 mg x l(-1) TSS residual) and 96.4% for turbidity
      (with 12.9 NTU residual), when the anaerobic reactor effluents have worst quality
      during the whole day.

PMID- 14640231
TI  - Performance of constructed wetland systems treating anerobic effluents.
AB  - The purpose of this present paper is to verify the performance of three wetland
      systems operated with effluents from a UASB reactor, with respect nutrient
      removal (nitrogen and phosphorus), pathogenic organisms and remaining
      carbonaceous material, monitored over a three-year period. The experiment was
      carried out and monitored at PROSAB (Programa de Saneamento Basico) in Campina
      Grande, Paraiba. The removal efficiency of the carbonaceous material expressed in
      DQO ranged from 70 to 86%, but concerning the total suspended solids, the
      efficiency ranged from 50 to 71%. The removal efficiency in terms of nitrogen and
      phosphorus of both vegetated systems was about 65.5 to 86%, respectively, during
      the first year of operation. Under the operational conditions of the experiment,
      the removal of phosphorus in a wetland system containing washed sand as the
      substratum decreased, as its operation period increased. The vegetated wetland
      has been the most efficient in removing faecal coliforms (roughly 4 log units) as
      compared to the non-vegetated one (about 3 log units), when both were operated
      with the same hydraulic load (2.3 cm. per day). Thus, the effluent produced over
      the three-year period ranged from 800 to 1,800 UFC/100 mL in the analyzed
      samples.

PMID- 14640232
TI  - A membrane assisted hybrid bioreactor for the post treatment of an anaerobic
      effluent from a fish canning factory.
AB  - An innovative membrane assisted hybrid bioreactor was used to treat a mixture of
      two streams produced in a fish canning factory: a highly loaded stream that had
      previously been treated in an anaerobic contact reactor, and a second stream with
      a relatively low COD and N concentration. Experiments were carried out during two
      experimental stages: an aerobic stage, which is focused in the study on the
      aerobic oxidation of ammonia and COD and a nitrification-denitrification stage in
      which the study was mainly focused on the removal of nitrogen. Results of the
      aerobic period pointed out that it was feasible to achieve ammonia and COD
      removals of around 99% at OLR of 6.5 kg COD/m3 x d and NLR of 1.8 kg N-NH4+/m3 x
      d. Specific nitrifying activities of up to 0.78 g N-NH4+/g protein x d and 0.25 g
      N-NH4+/g VSS x d, were recorded for the attached and suspended biomass,
      respectively. Around 50-60% of the nitrifying capacity of the reactor was a
      result of the nitrifying capacity of the biofilm. During the nitrification
      denitrification stage 76% of nitrogen removal was attained at an NLR of 0.8 kg N
      NH4+/m3 x d. The biofilm nitrifying activity was not affected by the operating
      conditions of the system, as a result of the preferential consumption of COD by
      suspended biomass in the reactor. Thus, the combination of a hybrid system, with
      both suspended and attached biomass, and an ultrafiltration membrane module might
      be an alternative for treating wastewaters in compact biological systems. The
      intrinsic characteristics of the system made it feasible to operate at high OLR
      without problems related with the settling properties of the sludge or the drop
      in the nitrogen conversion. There were no solids in the effluent as a result of
      the use of the membrane filtration module.

PMID- 14640233
TI  - Combined anaerobic-aerobic treatment of landfill leachates under mesophilic,
      submesophilic and psychrophilic conditions.
AB  - As a first step of treatment of landfill leachates (total COD--1,430-3,810 mg/l,
      total nitrogen 90-162 mg/l), a performance of laboratory UASB reactors has been
      investigated under mesophilic (30 degrees C), sub-mesophilic (20 degrees C) and
      psychrophilic (10 degrees C) conditions. Under hydraulic retention times (HRT) of
      around 7 h, when the average organic loading rates (OLR) were around 5 g
      COD/l/day, the total COD removal accounted for 81% (on the average) with the
      effluent concentrations close to anaerobic biodegradability limit (0.25 g COD/l)
      for mesophilic and sub-mesophilic regimes. The psychrophilic treatment conducted
      under the average HRT of 8 h and the average OLR of 4.22 g COD/l/day showed a
      total COD removal of 47% producing the effluents (0.75 g COD/l) more suitable for
      subsequent biological nitrogen removal. All three anaerobic regimes used for
      leachate treatment were quite efficient for elimination of heavy metals (Fe, Zn,
      Cu, Pb, Cd) by concomitant precipitation in the form of insoluble sulphides
      inside the sludge bed. The application of aerobic/anoxic biofilter as a sole
      polishing step for psychrophilic anaerobic effluents was acceptable for
      elimination of biodegradable COD and nitrogen approaching the current standards
      for direct discharge of treated wastewater.

PMID- 14640234
TI  - Extracorporeal treatments in sepsis: are there new perspectives?
AB  - Sepsis continues to provide a major challenge to clinicians. Despite vast
      advancements achieved in the understanding of its pathways and mechanisms, the
      incidence of sepsis is increasing and the mortality and morbidity rates remain
      high, generating a considerable burden to health budgets worldwide.
      Unfortunately, no definitive therapy yet exists that can successfully treat
      sepsis and its complications. At variance with targeting single mediators,
      therapeutic intervention aimed at the non-selective removal of pro- and anti
      inflammatory mediators seems a rational concept and a possible key to successful
      extra-corporeal therapies. A further advantage may lie in the continuous nature
      of such therapy. With such continuous therapy, sequentially appearing peaks of
      systemic mediator overflow may be attenuated and persistently high plasma levels
      reduced. This theoretical framework is proposed as the underlying biological
      rationale for a series of innovative modalities in sepsis. In this editorial, we
      will review recent animal and human trials which lend support to this concept. We
      will also review the importance of treatment dose during continuous renal
      replacement therapy as a major factor affecting survival in critically ill
      patients with acute renal failure. We will also review novel information related
      to other blood purification techniques using largo pore membranes or plasma
      filtration with adsorbent perfusion. Although these approaches are still in the
      early stages of clinical testing, they are conceptually promising and might
      represent an important advance.

PMID- 14640235
TI  - The number of CD10-positive glomerular epithelial cells reflects renal prognosis
      in IgA nephropathy patients.
AB  - BACKGROUND: The glomerular epithelial cells play an important role in glomerular
      filtration of the kidney. The disruption of these cells contributes to the
      development of glomerulosclerosis. The present study was performed to elucidate
      whether loss of the glomerular epithelial cells is associated with renal injury
      in patients with IgA nephropathy. PATIENTS AND METHODS: Thirty renal biopsy
      specimens from IgA nephropathy, 12 from minor glomerular abnormalities and 5 from
      normal controls were observed. The specimens from IgA nephropathy were divided
      into 2 groups: Group IgA-1, including 11 patients who had received a follow-up
      renal biopsy because of deterioration of renal function, and Group IgA-2,
      consisting of the remaining 19 patients without follow-up biopsy.
      Immunohistochemistry was performed using a monoclonal antibody against CD10
      antigen that appears on mature epithelial cells of glomeruli. RESULTS: The
      average number of CD10-positive glomerular epithelial cells (GECs) was
      significantly lower in IgA nephropathy than in either minor glomerular
      abnormalities or the normal controls. In IgA nephropathy, there were significant
      correlations of the GECs with renal functions. The GECs were reduced along with
      the progression of histopathological damage. In group IgA-1, the GECs were
      significantly reduced at the second biopsy compared with the first biopsy, and
      significantly fewer in group IgA-1 than in group IgA-2 at the first biopsy. The
      GECs showed a significant correlation with renal prognosis during the follow-up
      period. CONCLUSIONS: The reduction of GECs was associated with renal dysfunction,
      histopathological damage and renal prognosis. The GECs may be a useful predictor
      of renal prognosis in IgA nephropathy.

PMID- 14640236
TI  - Is biopsy required prior to cyclophosphamide in steroid-sensitive nephrotic
      syndrome?
AB  - AIM: The present studywas designed to retrospectively evaluate the use of renal
      biopsies prior to cyclophosphamide therapy. The aim of the study was to determine
      in how many cases histological outcome of the biopsies had subsequently changed
      the decision to treat or refrain from treatment. PATIENTS AND METHODS: Between
      January 1980 and September 2001, 85 children with steroid-sensitive nephrotic
      syndrome (SSNS) underwent a renal biopsy in the University Hospitals of Utrecht
      and Nijmegen before the start of an 8-week cyclophosphamide treatment. MCNS was
      suspected in all children because of the following criteria: edema, proteinuria,
      hypoalbuminemia, absence of macroscopic hematuria and in rare cases microscopic
      hematuria, no permanent hypertension, normal C3 serum level, a normal glomerular
      filtration rate as determined by creatinine clearance and age > 1 year.
      Cyclophosphamide therapy was indicated because of a frequently relapsing (FR)
      course of illness in 8 children, because of steroid dependence (SD) in 22
      children and because of combined FR and SD in 55 children. Steroid-resistant
      children were excluded from this study. RESULTS: Histology confirmed the
      diagnosis MCNS in 84 out of 85 children. In addition to MCNS, IgA deposits were
      observed in renal specimens of 2 children. In 1 SD child, the initial diagnosis
      MCNS was changed 3 years later when a repeated biopsy showed progression into
      focal segmental glomerulosclerosis (FSGS). CONCLUSION: In summary, no renal
      biopsy is required prior to cytotoxic therapy in children with uncomplicated
      steroid-sensitive nephrotic syndrome.

PMID- 14640237
TI  - The effects of dual blockade of the renin-angiotensin system on urinary protein
      and transforming growth factor-beta excretion in 2 groups of patients with IgA
      and diabetic nephropathy.
AB  - AIMS: The therapeutic benefits of dual blockade of the renin-angiotensin system
      (RAS) have been inconsistent on renal function and proteinuria. To know the
      contribution of the heterogeneity of study subjects to such inconsistency, we
      evaluated the effects of dual blockade of RAS in 2 groups of selected renal
      diseases, IgA and diabetic nephropathy. To avoid confounding by the blood
      pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added
      on the patients with long-term, optimally controlled blood pressure taking ACE
      inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1
      level were measured as surrogate markers of renal injury. METHODS: We conducted a
      prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy
      patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal
      dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose
      of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5
      mg/day for 16 weeks. RESULTS: All baseline data except for the age factor were
      statistically the same between the 2 disease groups. Twenty-four-hour mean
      arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and
      diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial
      pressure did not change by the addition of candesartan or placebo in both groups.
      The addition of candesartan (combination) reduced 24-hour urinary protein
      excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%,
      which is significantly greater compared to a mean change of -0.1 +/- 3.3% after
      the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 -
      23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the
      combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly
      different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3;
      p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not
      reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary
      protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/-
      6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The
      level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/-
      9.5% decrease, but it did not reach statistical significance compared to placebo
      of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour
      urinary protein excretion rate and urinary TGF-beta1 level were neither
      correlated with each other, nor with the change in mean arterial pressure.
      Significant changes in the renal function were not detected during the study
      period. CONCLUSION: Definite beneficial effects of dual blockade of RAS on
      proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which
      was independent of blood pressure-reducing effect. With our 16-week trial, such
      benefits were not observed in type 2 diabetic nephropathy. The reduction in
      urinary TGF-beta1 level suggests that the combination therapy may provide
      additional renoprotection through the antisclerosing effects. Based on our
      results, for a proper interpretation the therapeutic effects of the combination
      therapy should be evaluated separately according to the underlying renal disease.

PMID- 14640238
TI  - Interleukin-18, interleukin-18 binding protein and impaired production of
      interferon-gamma in chronic renal failure.
AB  - Uremia is associated with suppressed cellular immune responses, manifested, in
      part, by impaired interferon-gamma (IFNgamma) production. We investigated the
      influence of kidney function on plasma levels of interleukin-18 binding protein
      (IL-18BP), the naturally occurring inhibitor of IL-18. METHODS: Plasma levels of
      IL-18, IL-18BP and IFNgamma were measured by specific immunoassays in patients
      with normal kidney function (NKF, n = 29), in patients with chronic renal
      insufficiency (CRI, n = 29), and in patients on hemodialysis (HD, n = 40). In
      addition, Staphylococcus epidermidis-induced production of IFNgamma and IL-18 in
      whole blood cultures was determined in 12 patients on HD and compared to
      production in 9 controls with NKF. RESULTS: Plasma IL-18 (mean +/- SEM) in NKF
      was 17.9 +/- 3.6 pg/ml, in CR142.6 +/- 7.0 pg/ml (p < 0.01), and in HD 93.5 +/-
      13.6 pg/ml (p < 0.001). The level of IL-18BP in NKF was 3.4 +/- 0.4 ng/ml, in CRI
      7.5 +/- 0.7 ng/ml (p < 0.001), and in HD 13.1 +/- 0.8 ng/ml (p < 0.001). Plasma
      IL-18BP was inversely correlated with creatinine clearance (correlation
      coefficient: -0.7479). The level of free IL-18 was calculated in NKF to be 13.8
      +/- 3.3 pg/ml, in CRI 23.6 +/- 3.9 pg/ml (not significant), and in HD 39.6 +/-
      5.9 pg/ml (p < 0.001). Stimulated whole blood production of IFNgamma in NKF was
      185 +/- 74 pg/10(6) mononuclear cells (PBMC), but suppressed in HD to 27.3 +/- 16
      pg/10(6) PBMC (p < 0.05). CONCLUSION: In uremia, retention of IL-18BP does not
      suffice to neutralize most of the concomitantly raised levels of total IL-18
      resulting in elevated levels of free IL-18. Nevertheless, IFNgamma production in
      whole blood is reduced in patients on HD. Therefore, suppression of IFNgamma
      production in uremia may be due to inhibitors of IFNgamma production other than
      IL-18BP.

PMID- 14640239
TI  - Targeting higher ferritin concentrations with intravenous iron dextran lowers
      erythropoietin requirement in hemodialysis patients.
AB  - INTRODUCTION: Although clinical use of recombinant human erythropoietin (rHuEPO)
      since 1989 has improved anemia in most end-stage renal disease patients, there
      are still many hemodialysis patients unable to maintain an adequate hematocrit
      (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a
      consequence of rHuEPO deficiency, but may be due to other factors including
      functional iron deficiency. Since the optimal prescription for iron replacement
      is not yet known, we evaluated the effect of intravenous iron dextran (IVFe)
      infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective
      was to raise and maintain serum ferritin concentrations to 2 different levels
      above the National Kidney Foundation Dialysis Outcome Quality Initiative standard
      of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be
      lowered. METHODS: HD patients on i.v. rHuEPO with a SFer concentration > or = 70
      ng/ml and an HCT of < or = 33% were enrolled. Subjects were divided as follows:
      Group 1: target SFer of 200 ng/ml, Group 2: target SFer of 400 ng/ml. Each
      subject below the target level received IVFe in up to 10 divided doses during
      consecutive dialysis sessions as needed to reach the target. HCT was maintained
      between 32.5% and 36% by adjusting rHuEPO dosage. RESULTS: Mean SFer
      concentration at the study conclusion in Group 1: 261 ng/ml; Group 2: 387 ng/ml.
      The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week (250 -
      219 U/kg bw/wk) while in Group 2 it was 154 U/kg body weight/week (312 - 158 U/kg
      bw/wk) (p < 0.001). There was no difference in HCT between groups. Our results
      suggest that higher target serum ferritin concentrations can be well tolerated
      and lower rHuEPO requirements.

PMID- 14640240
TI  - Quality of life in patients treated with hemodialysis or peritoneal dialysis:
      what are the important determinants?
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) have significant
      impairments in health-related quality of life (HRQOL). In part, this is due to
      the intrusiveness of the treatment (hemodialysis or peritoneal dialysis) that is
      required. It is unclear whether hemodialysis or peritoneal dialysis is associated
      with a higher HRQOL. METHODS: 192 prevalent patients who self-selected treatment
      with hemodialysis (either in-center, satellite or home/self-care hemodialysis) or
      peritoneal dialysis were studied to determine whether treatment with hemodialysis
      or peritoneal dialysis is associated with a higher HRQOL. Demographic, laboratory
      and clinical information (including the presence of comorbid conditions using the
      Charlson comorbidity index) was assessed at baseline. The outcome of interest was
      HRQOL, which was measured using the Kidney Disease Quality of Life-Short Form
      (KDQOL-SF), the Short-Form 36 (SF-36) and the EuroQol EQ-5D at baseline and after
      6 and 12 months of follow-up. RESULTS: There was no significant difference in
      HRQOL scores for the SF-36, the EQ-5D and for 9 of 11 KDQOL dimensions for
      patients treated with hemodialysis or peritoneal dialysis at baseline. As
      expected, HRQOL was significantly lower for patients who had more comorbid
      disease, required assistance with their daily care, and for patients with less
      than a grade 12 education. After controlling for the effect of other important
      variables, HRQOL (as measured by the EQ-5D visual analog or index scores) did not
      differ between hemodialysis and peritoneal dialysis patients. HRQOL was stable
      over time, both for patients who started on hemodialysis or peritoneal dialysis.
      CONCLUSIONS: There is no significant difference in HRQOL for prevalent ESRD
      patients treated with hemodialysis or peritoneal dialysis. It will be important
      to determine if this finding holds true for incident patients treated with
      hemodialysis or peritoneal dialysis.

PMID- 14640241
TI  - The epidemic of aging in renal replacement therapy: an update on elderly patients
      and their outcomes.
AB  - BACKGROUND: In the past 2 decades, a rapid growth has occurred in the number of
      patients over 65 years of age accepted for renal replacement therapy (RRT) with
      an increasing need for dialysis resources as a consequence. The aim of this study
      is to describe the trends in incidence, treatment and outcome of RRT of these
      elderly patients included in the new ERA-EDTA Registry database. METHODS: Data
      from 6 national renal registries have been included for the period 1985 - 1999,
      comprising data of 18,920 elderly patients starting RRT. We used Cox-proportional
      hazards regression to predict patient and technique survival. RESULTS: The
      incidence and prevalence of RRT showed a 4- to 5-fold increase over the period,
      resulting in 48% of the new patients being older than 65 years in 1999. However,
      the rates varied considerably between countries. The 2-year patient survival was
      51% in dialysis patients. Mortality due to social causes increased with age.
      Multivariate analysis showed no change with time in patient survival on dialysis,
      but the risk of death following a first renal allograft between 1995 and 1999 was
      reduced by 31%, compared with the 1985 - 1989 time period (RR 0.69; 95% CI: 0.54 
      0.90). The relative risk of peritoneal dialysis technique failure was more than
      doubled in the 1995 - 1999 cohort compared to the 1985 - 1989 cohort (RR 2.38;
      95% CI: 1.89 - 3.01), with the highest technique failure rate in the first 2
      years of the 1995 - 1999 cohort. CONCLUSIONS: The number of elderly patients
      receiving RRT is rising rapidly. Patient survival on dialysis has been stable
      over the last 15 years, whereas transplant outcome has improved. The increased
      peritoneal dialysis technique failure and the high mortality due to social causes
      in the elderly age groups require further investigation. The challenge of the
      years ahead is to provide this life-prolonging therapy to all patients who need
      it in such a way that it improves quality of life and at a cost that a society
      can afford.

PMID- 14640242
TI  - HCV and renal disease: not always associated with mixed cryoglobulinemia.

PMID- 14640243
TI  - Crescentic fibrillary glomerulonephritis associated with hepatitis C viral
      infection.
AB  - Fibrillary glomerulonephritis (FGN) is a pathological diagnosis that is rarely
      associated with systemic disorders. In this case report, we describe a woman who
      presented with FGN of the crescentic type in association with hepatitis C viral
      infection. The existing literature on the association between these 2 disorders
      is reviewed, and postulated therapy is presented.

PMID- 14640244
TI  - Development of hungry bone syndrome after rapid lowering of PTH with intravenous
      maxacalcitol therapy in a patient with non-uremic secondary hyperparathyroidism.
AB  - A 41 year-old woman complained of general bone pain and polyuria. She did not
      have Albright hereditary osteodystrophy. Laboratory examination revealed
      hypokalemia, hypocalcemia, and an elevation of serum intact PTH concentration.
      The patient was polyuric and relatively hypercalciuric, though her glomerular
      filtration rate (GFR) was normal. Neither urinary Pi nor cAMP excretion was
      remarkably promoted by an exogenous PTH load. An iliac bone biopsy revealed
      osteopenia, active osteoclastic bone resorption, fibrous transformation in bone
      marrow tissue, and severely disturbed calcification. Although the oral
      administration of alfacalcidol showed no effects, 3 weeks of intermittent
      intravenous injection of maxacalcitol therapy decreased the serum intact PTH
      concentration from 597 pg/ml to 40 pg/ml, and the bone pain was greatly relieved.
      However, plasma Ca concentration also decreased and symptoms of tetany appeared.
      Pseudohypoparathyroidism type Ib was the most likely diagnosis in this patient.
      In conclusion, maxacalcitol therapy satisfactorily suppressed parathyroid
      function in a patient with secondary hyperparathyroidism without uremia.
      Appropriate Ca supplementation was required to perform it safely.

PMID- 14640245
TI  - Reply to Kisters. "Effects of candesartan and amlodipine on renal function and
      electrolytes in renal allograft recipients".

PMID- 14640246
TI  - Peritoneal dialysis in a nursing home: limited survival expectations.

PMID- 14640247
TI  - Understanding cardiovascular health in women: it's a two-way street.

PMID- 14640248
TI  - What is the new tax act and why should I care about it?

PMID- 14640249
TI  - Looking for mentor replacement therapy? A coach may be the answer.
AB  - How can women physicians address the needs of those they serve until they meet
      their own needs for balance and fulfillment in their lives and careers? They
      can't, but there are sources of help. Women physicians can learn from consultants
      whose professional expertise can help them devise master plans to attain
      equilibrium, competence, and influence, and they can speak with other women
      physicians who share similar experiences and have succeeded in attaining
      stability, proficiency, and authority in their own lives. Career development
      coach and faculty career and diversity consultant Janet Bickel writes that
      seasoned professionals offer assistance in planning for productive careers that
      combine personal and professional goals. To find a coach, ask colleagues about
      their experiences and for recommendations. When selecting a coach, inquire about
      their training and credentials; ask for a free consultation and for references.
      Interview at least three coaches before making a selection. A coach with a
      similar background may provide the most comfortable working relationship. Ms.
      Bickel offers suggestions and programs to consider when seeking a career coach.
      Physicians Julia Files and Janis Blair address the multiple responsibilities of
      motherhood and medicine. Their experiences and tips from colleagues demonstrate
      that women in search of harmony benefit from others' knowledge and wise advice.
      Talking with colleagues lessens the feeling of isolation; all mothers who aspire
      to be the best at medicine and motherhood worry that achieving a healthy balance
      may be impossible. Drs. Files and Blair share strategies that worked for them and
      their colleagues at the Mayo Clinic.

PMID- 14640250
TI  - In search of balance: medicine, motherhood, and madness.
AB  - Women physicians have made great strides not only in gaining acceptance but also
      in excelling in the medical profession. A large minority of physicians today are
      women. Success in the dual roles of mother and physician really is possible, and
      the experience offers a uniquely rich and complex life. Our hope is that the
      practical suggestions offered here will prove useful to the next generation of
      women physicians and that each subsequent generation will become ever more
      successful in filling these roles.

PMID- 14640251
TI  - Unauthorized practice: teaching pelvic examination on women under anesthesia.
AB  - Medical ethics evolved over the past half-century. This brought close
      reexamination and scrutiny of medical education and the "hands-on training" of
      future medical practitioners. Likewise societal opinions have intensified
      regarding the rights of patients, especially those deemed less likely to express
      their humiliation if they should discover themselves in compromising positions
      during treatment. Informed consent is modern medico-legal terminology; if the
      public felt that all patients were treated with the self-determination and
      dignity required by current HIPAA regulations, then there would be no reason to
      legislate such requirements. Law professor Robin Fretwell Wilson, Esq., and
      obstetrics and gynecology professor Nancy G. Chescheir, MD, present evidence and
      opinions from the legal and medical perspectives regarding conducting pelvic
      exams on anesthetized women without or with vague consent.

PMID- 14640252
TI  - Moral diversity among physicians and conscientious refusal of care in the
      provision of abortion services.
AB  - Physicians are independent moral agents whose values, like those of
      nonphysicians, are shaped by personal experience, religious beliefs, family, and
      lifetime mentors. Most individuals are free to exercise their moral values in the
      ways that they see fit within the boundaries of legality. Physicians' moral
      values take on special significance, however, when considering services patients
      may request but that contradict that physician's moral beliefs, such as
      termination of pregnancy. In this article I analyze the competing obligations to
      self and to patient that a conscientiously objecting physician must consider when
      his or her personal morality affects his or her relationship with the patient.
      Despite each physician's freedom to choose his or her mode of practice and which
      services to provide, a physician with a moral viewpoint that would prevent even
      counseling on certain options should consider practicing in an area of medicine
      in which the patient's right to full disclosure of options and informed consent
      is not compromised by the physician's personal moral stance.

PMID- 14640253
TI  - Women in cardiac rehabilitation.
AB  - Women have been underrepresented in both cardiac rehabilitation (CR) clinical
      care and research studies. This review summarizes the available data on women in
      CR, including referral and enrollment patterns, baseline characteristics, and sex
      specific outcomes reported within each core component of care. Women in CR tend
      to be older than their male counterparts and to have a greater burden of
      comorbidities and coronary risk factors and lower functional status. Women and
      men seem to benefit equally from CR, with improvements in clinical, psychosocial,
      and behavioral outcomes, but sex-specific data are lacking for several of the
      core components of care. Future research needs to test single and multiple
      behavioral interventions in randomized controlled trials, paying particular
      attention to their sex specificity, feasibility, and cost-effectiveness within CR
      and secondary prevention programs.

PMID- 14640254
TI  - Menopausal hormone therapy and cardiovascular protection: state of the data 2003.
AB  - Despite biologically plausible mechanisms for cardiac protection from estrogen
      therapy and observational data suggesting that hormone therapy confers
      cardiovascular benefit, the outcomes of well-designed and conducted primary and
      secondary prevention randomized clinical trials have documented cardiovascular
      risk rather than benefit. Menopausal hormone therapy failed to prevent clinical
      cardiovascular events in healthy menopausal women and in those with established
      coronary heart disease. Rather, it increased the risk of coronary heart disease
      events, particularly myocardial infarction, stroke, and venous thromboembolism,
      as well as that of breast cancer. Recommendations from the US Preventive Services
      Task Force emphasize that, for most women, the harms of hormone use are likely to
      exceed the benefits for the prevention of chronic disease. Women should talk with
      their health care providers about such proved approaches to coronary risk
      reduction as smoking cessation, heart-healthy diet, physical activity, weight
      management, and pharmacologic control of hypertension and hypercholesterolemia.

PMID- 14640255
TI  - Lipids in women: screening and treatment.
AB  - Hyperlipidemia is a risk factor for coronary heart disease (CHD) in both men and
      women, although the association between total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, and CHD risk
      differs in men and women. Although several clinical trials of lipid lowering for
      both primary and secondary prevention of CHD have been conducted, women have not
      always been included, have been included in small numbers, or have not had their
      results analyzed separately. CHD risk assessment is an important component of
      decision making about screening and treatment of hyperlipidemia. This article
      presents guidelines for screening and treatment of hyperlipidemia in women with
      CHD, in healthy women, and in women at risk for CHD.

PMID- 14640256
TI  - Psychosocial factors predict coronary heart disease, but what predicts
      psychosocial risk in women.
AB  - OBJECTIVES: Psychosocial factors, including depression, anger, and social
      isolation, have been associated with increased morbidity and mortality from
      coronary heart disease (CHD), but predictors of psychosocial burden among women
      with CHD are poorly defined. The purpose of this study was to determine whether
      readily measured demographic and risk factors could identify women with
      psychosocial risk factors that are more difficult to assess in a clinical
      setting. METHODS: Baseline data on 304 women (mean age 62 years, 52% minority)
      hospitalized with CHD at 3 academic medical centers participating in a clinical
      study of adherence to prevention guidelines were evaluated. Standardized
      questionnaires were used to measure depression (4-item self-report tool from the
      Primary Care Evaluation of Mental Disorders questionnaire) and anger (Spielberger
      Trait Anger Scale). One self-report question was used to assess social isolation.
      RESULTS: Thirty-seven percent of women with CHD reported depression, 50% reported
      anger, and 41% reported social isolation. In a logistical model controlling for
      confounders, independent predictors of depression were having dependents (odds
      ratio [OR] = 2.27, p = .006), age (< or = 65 years) (OR = 1.91, p = .02), and
      exercise (< 3 days/week) (OR = 3.92, p < .001). Anger was associated with having
      dependents (OR = 3.16, p < .001), age (< or = 65 years) (OR = 1.95, p = .02), and
      smoking (OR = 2.05, p = .04). Subjects who had dependents (OR = 2.24, p = .005),
      were unemployed (OR = 1.93, p = .03), and who did not get enough exercise (< 3
      days/week) (OR = 2.07, p = .03) reported higher isolation in adjusted models.
      Differences in prevalence of psychosocial factors by ethnicity were not
      statistically significant. However, there was a trend toward increased prevalence
      of psychosocial risk factors among white women, possibly reflecting the need for
      more culturally sensitive screening tools. CONCLUSION: These data may be helpful
      in identifying women who are at risk of increased CHD morbidity and mortality
      because of psychosocial burden.

PMID- 14640257
TI  - Noninvasive cardiac testing in women.
AB  - Coronary artery disease (CAD) is a leading cause of morbidity and mortality among
      men and women. Although substantial research efforts have refined diagnosis and
      treatment strategies for patients at risk, the detection of CAD in women can be
      problematic. Atypical chest pain is not only more common among women than men,
      but the predictive value of traditional risk factors is also different for women
      and men. Moreover, sex-specific issues in the selection of an appropriate
      noninvasive diagnostic test must be considered. This article reviews the
      challenges inherent in the evaluation of chest pain in women as well as the
      strengths and limitations of the diagnostic stress-testing modalities commonly
      used.

PMID- 14640258
TI  - Percutaneous coronary intervention in women.
AB  - Cardiovascular disease is currently the leading cause of death in women in the
      United States, but many women underestimate this risk. The treatment of coronary
      syndromes with percutaneous coronary intervention (PCI) has increased steadily in
      the past decade, but women referred for PCI have a different profile of
      demographic features and clinical presentation than do their male counterparts.
      Concern has been raised about sex discrepancy in referral of women for invasive
      cardiology procedures. This may have resulted from the outcomes of initial
      studies of balloon angioplasty, which demonstrated decreased success and
      increased risk of angioplasty in women compared with men. However, more recent
      data have shown no sex difference in outcomes with contemporary PCI practices.
      Additionally, primary PCI for acute myocardial infarction in women is associated
      with improved mortality in women when compared to thrombolytic therapy. This
      review will examine the sex differences in demographics and outcomes of women
      undergoing PCI.

PMID- 14640259
TI  - Platelet hyperreactivity in women from families with premature atherosclerosis.
AB  - OBJECTIVES: This study was designed to determine whether sex differences in
      platelet function exist in families with premature atherosclerosis. Compared with
      men, women have a greater risk of death and recurrent events following myocardial
      infarction and coronary artery bypass graft surgery. The reasons for this sex
      discrepancy are unknown. Because blood platelets play a central role in the
      formation of pathologic thrombi at sites of ruptured atheromatous plaques, we
      postulated that sex differences in platelet function exist that may be partly
      responsible for the sex difference in coronary artery disease (CAD) outcomes.
      METHODS: We compared platelet reactivity in 400 asymptomatic men and women with
      family histories of premature CAD. Subjects were participants in the Johns
      Hopkins Sibling Study, a prospective investigation of coronary risk factors in
      asymptomatic, apparently healthy siblings of people with documented CAD. RESULTS:
      The platelets from women bound more fibrinogen in response to low and high
      concentrations of adenosine diphosphate. This sex difference was greater in
      whites than in African Americans. Age did not have an impact on these findings,
      although platelets from women 48 to 59 years old tended to bind less fibrinogen
      than those younger than 48 years. Female platelets also demonstrated greater
      spontaneous aggregation compared with male platelets, and women had higher levels
      of plasma thromboxane than men did. These differences were independent of
      smoking, hypertension, diabetes, hypercholesterolemia, or aspirin use.
      CONCLUSIONS: In asymptomatic individuals with family histories of premature CAD,
      platelets from women are more reactive than platelets from men. This observation
      cannot be explained by differences in cardiac risk factors.

PMID- 14640260
TI  - Modifiable risk factors for the primary prevention of heart disease in women.
AB  - Coronary heart disease is the leading cause of death in women older than 50. This
      article will discuss the role of modifiable risk factors for the primary
      prevention of heart disease in women, including hypertension, smoking, obesity,
      and exercise. We will also address what is known about the role of psychological
      factors in the development of heart disease in women. Cholesterol and diabetes
      are discussed only in the context of obesity because both are addressed elsewhere
      in this issue. Finally, this article will review the evidence on the use of low
      dose aspirin and antioxidants in the primary prevention of heart disease in
      women.

PMID- 14640261
TI  - The gift.

PMID- 14640262
TI  - Discriminant function sexing of the calcaneus of the South African whites.
AB  - The skull and some postcranial elements, such as the humerus, femur, and tibia,
      have been used in their intact states for sex determination in forensic and
      archaeological cases. But, in practice, these bones are often recovered in
      fragmented states, which render them unsuitable for use in sex determination. The
      calcaneus is a compact bone that is able to withstand high tensile forces. Some
      of its parameters have been used for sex determination in American whites and
      blacks (1) and Italians (2). This bone has not been used for sex determination in
      the South African white population. Therefore, the aim of this study was to
      assess the degree of sexual dimorphism of the calcaneus of the South African
      white population sample, derive discriminant function score equations for use in
      sex determination, and determine the level of accuracy of its sex-determining
      ability. Nine parameters were measured on each pair of 53 male and 60 female
      calcanei of known South African white skeletons, obtained by a random sampling
      technique from the Raymond A. Dart Collection of Human Skeletons, School of
      Anatomical Sciences, University of the Witwatersrand, Johannesburg. Basic
      statistic and discriminant function analysis was performed on the acquired data.
      The basic statistics showed that all measured parameters were sexually dimorphic.
      Discriminant function score equations were generated for use in sex
      determination. The average accuracy of sex classification ranged from 73 to 86%
      for the univariate method, 81 to 91% for the stepwise method, and 82 to 92% for
      the direct method. It is concluded that the calcaneus is useful for sex
      determination in the South African white population.

PMID- 14640263
TI  - Bilateral fractures of the coronoid processes: differential diagnosis of intra
      oral gunshot trauma and scavenging using a sheep crania model.
AB  - Approximately half of the skeleton of an adult male (minus the cranium) was found
      in a forested part of Greater Vancouver, Canada, in August 2000 by the Royal
      Canadian Mounted Police (RCMP). Authorities ruled the death as suicide. The only
      compelling signs of perimortem trauma were symmetrically fractured coronoid
      processes of the mandible, which can be attributed to a gunshot in the mouth.
      However, the remains had also been scavenged by canids, raising a problem in
      differential diagnosis. Could canid scavenging produce bilateral fracturing of
      the mandible indistinguishable from gunshot wounds to the mouth? We found that
      canid scavengers could not mimic the type of damage to the mandible caused by
      intra-oral gunshot wounding using a sheep model (n = 20). Bilateral fracturing of
      the coronoid processes was found to be characteristic of intra-oral gunshot
      wounding, while canid scavengers typically ignore this region of the mandible.

PMID- 14640264
TI  - Utility of dorsal pits and pubic tubercle height in parity assessment.
AB  - Parity indicators in human skeletal material are highly desirable yet elusive. In
      this study, the relationships of dorsal pits and pubic tubercle elongation to
      parity are investigated in a sample of 148 modern female sets of pubic bones with
      associated birth information. The elongation of the pubic tubercle shows no
      significant correlation with number of births, but instead is associated with the
      distance this feature is from the pubic symphysis (p < 0.01) and the size of the
      arcuate angle (p < 0.05). Dorsal pits show a strong association with increasing
      numbers of births (p < 0.01), especially in younger women. However, in women over
      50 years old, dorsal pitting is correlated with BMI (p < 0.05) and is not
      significantly correlated with number of births. While this study lends support to
      the correlation of dorsal pitting and parity, it currently does not reach the
      level of accuracy needed for forensic applications at the level of the
      individual.

PMID- 14640265
TI  - New developments in SPME, Part 1: The use of vapor-phase deprotonation and on
      fiber derivatization with alkylchloroformates in the analysis of preparations
      containing amphetamines.
AB  - Due to their high polarity and low vapor pressure, most amine salts of
      amphetamine-type drugs are not directly amenable to headspace recovery using
      solid-phase microextraction (SPME). Described in this article is a simple vapor
      phase procedure for the conversion of solid drug salt samples into their free
      bases by the use of triethylamine. This process can be conducted simultaneously
      with headspace SPME, the outcome being that solid drug salts can be sampled
      directly for GC-MS without the need for dissolution and chemical processing.
      Potential applications for this methodology include the noninvasive recovery of
      drug traces from objects such as banknotes and garments. This new process for
      recovery of amphetamine-type drugs has been combined with on-fiber derivatization
      using alkylchloroformates. This extra step was included to improve the
      chromatographic performance of analytes and allow for the resolution of drug
      enantiomers.

PMID- 14640266
TI  - A clustering algorithm using DNA marker information for sub-pedigree
      reconstruction.
AB  - In a mass disaster scenario in which many people are dead, it may be that small
      family groups are among the dead, and investigators may need to identify such
      groups, e.g., to return bodies to living relatives for burial. We consider the
      problem of identifying small groups of closely related people within a large
      group of people through the use of DNA marker information. We propose a
      likelihood-ratio-based distance measure of the relatedness between pairs of
      individuals and use an estimate of this measure as a means of clustering related
      people into groups. We show the effectiveness of our approach on real examples
      and through simulations, which suggest that the method is quite reliable for
      identifying very close relationships. We discuss the use of our clustering
      algorithm in a two-stage pedigree reconstruction procedure and suggest directions
      in which the analysis could be extended. Applications include the identification
      of family groups among bodies found in mass graves and identification of family
      groups in animal populations.

PMID- 14640267
TI  - Chemical profiling of 3,4-methylenedioxymethamphetamine (MDMA) tablets seized in
      Hong Kong.
AB  - During 2000-2001, the Government Laboratory of Hong Kong received over 600,000
      ecstasy tablets in more than 2,600 cases. Using GC-MS or FTIR, the major
      amphetamine-type stimulants were identified, and the samples were categorized
      into four groups containing: (1) 3,4-methylenedioxymethamphetamine (MDMA), (2)
      methamphetamine (MA), (3) 3,4-methylenedioxyamphetamine (MDA), or (4)
      amphetamine. Our study revealed that in Hong Kong MDMA tablets have made up 98
      and 71% of the total ecstasy tablets examined in 2000 and 2001, respectively.
      Among the MDMA cases, 613 cases involving a total of 123,776 tablets in 2001 were
      randomly selected, and their active ingredients, minor ingredients, and/or
      impurities were studied using GC-MS and HPLC. Based on the chemical profiles, and
      irrespective of their different physical characteristics, tablets obtained in
      different seizures could be determined as to whether or not they could have come
      from a common origin. The impurities detected in the MDMA tablets also served as
      excellent chemical markers from which plausible synthetic route(s) of the MDMA
      were inferred. Our study revealed that 3,4-methylenedioxyphenyl-2-propanone
      (MDP2P), 3,4-methylenedioxyphenyl-2-propanol (MDP), 3,4-methylenedioxy-N
      methylbenzylamine (MDB), piperonal and N-formyl-3,4-methylenedioxymethamphetamine
      (N-formyl-MDMA) were the most common impurities detected in MDMA tablets seized
      in Hong Kong. The finding of the phosphate salt of MDMA is intriguing. Based on a
      presumptive color test, spectroscopic data (FTIR/ESI-MS) and the percentage of
      MDMA content in a purified phosphate salt of MDMA, the ratio of the phosphate to
      MDMA was determined to be 1:1, suggesting that the compound is a dihydrogen
      phosphate salt [i.e. (HMDMA)H2PO4].

PMID- 14640268
TI  - Validation and uses of a Y-chromosome STR 10-plex for forensic and paternity
      laboratories.
AB  - Y-chromosome short tandem repeats (Y-STRs) provide valuable information in cases
      of rape and questioned paternity, and they allow for the genetic identification
      of male lineages. The present study validated a Y-STR 10-plex on the ABI PRISM
      3100 Genetic Analyzer for use in forensic and paternity laboratories at Orchid
      Cellmark. Following optimization of the polymerase chain reaction, father-son
      pairs were analyzed to ensure that each pair generated identical haplotypes. This
      study demonstrated that the 10-plex is sensitive to 0.125 ng of input DNA and
      that female samples mixed with male samples did not interfere with Y-STR
      haplotyping. In a sample of 525 males, there were three instances of locus
      multiplication, two at DYS19 and one at DYS435. Overall, haplotype diversity was
      0.996, suggesting that the 10-plex can effectively distinguish among male
      lineages.

PMID- 14640269
TI  - A new method for collection and identification of gunshot residues from the hands
      of shooters.
AB  - This work presents a novel collection method for gunshot residues (GSR) using a
      sampling procedure based on ethylenediaminetetraacetic acid (EDTA) solution as a
      complexing agent on moistened swabs. Detection was via a sector-field inductively
      coupled plasma mass spectrometry (HRICP-MS). The proposed collection and
      analytical method allowed detection of antimony (Sb), barium (Ba) and lead (Pb)
      after .38 shot tests. at detection limits of less than 1 microg L(-1) in four
      different areas of the hands of volunteers. This paper includes a discussion
      concerning hand areas near the thumb and forefinger as being more suitable for
      GSR collection as well as a comparison between differences observed using 2%
      diluted EDTA. 2% nitric acid solution, and simple deionized water as collecting
      solutions, proving the superior efficiency of EDTA in GSR recoveries.

PMID- 14640271
TI  - Rapid quantification and sex determination of forensic evidence materials.
AB  - DNA quantification of forensic evidence is very valuable for an optimal use of
      the available biological material. Moreover, sex determination is of great
      importance as additional information in criminal investigations as well as in
      identification of missing persons, no suspect cases, and ancient DNA studies.
      While routine forensic DNA analysis based on short tandem repeat markers includes
      a marker for sex determination, analysis of samples containing scarce amounts of
      DNA is often based on mitochondrial DNA, and sex determination is not performed.
      In order to allow quantification and simultaneous sex determination on minute
      amounts of DNA, an assay based on real-time PCR analysis of a marker within the
      human amelogenin gene has been developed. The sex determination is based on
      melting curve analysis, while an externally standardized kinetic analysis allows
      quantification of the nuclear DNA copy number in the sample. This real-time DNA
      quantification assay has proven to be highly sensitive, enabling quantification
      of single DNA copies. Although certain limitations were apparent, the system is a
      rapid, cost-effective, and flexible assay for analysis of forensic casework
      samples.

PMID- 14640270
TI  - Novel paternity testing by distinguishing parental alleles at a VNTR locus in the
      differentially methylated region upstream of the human H19 gene.
AB  - Conventional PCR-based genotyping is useful for forensic testing but cannot be
      used to determine parental origins of alleles in DNA specimens. Here we describe
      a novel method of combined conventional genotyping and PIA typing (parentally
      imprinted allele typing) at a minisatellite region upstream from the H19 locus.
      The PIA typing uses two sets of primers and DNA digested with methylation
      sensitive Hha I enzyme. The first amplification produces only the methylated
      fragment of paternal H19 allele, and the second detects polymorphism in the
      minisatellite. Hence, this distinguishes paternal and maternal alleles by
      difference in the DNA methylation. Furthermore, the polymorphism in this
      polymorphic locus was examined using 199 unrelated Japanese and 171 unrelated
      Germans, their polymorphism information content being 0.671 and 0.705,
      respectively. Feasibility of this typing is demonstrated for six families, and
      the usefulness is shown by application to paternity testing.

PMID- 14640272
TI  - Optimization and initial evaluation of 1,2-indandione as a reagent for
      fingerprint detection.
AB  - 1,2-Indandione has been used to develop fluorescent fingerprints on porous
      materials such as paper. The compound reacts with amino acid residues to produce
      highly fluorescent fingerprint ridges. An optimized formulation and treatment
      protocol for using the reagent is presented here. The reagent is applied as a
      solution in HFE7100 containing acetic acid and ethyl acetate. Treated articles
      are heated at 100 degrees C for 10 min at ambient humidity and stored in the dark
      before recording the fingerprints using fluorescence photography or digital
      imaging. Photodecomposition of the fluorescent fingerprints has been observed.
      Storage in the dark reduces degradation, extending the lifetime of the
      fingerprints. Other chemical methods to stabilize the fingerprints proved
      unsuccessful. Comparisons of the performance of 1,2-indandione with DFO in CFC113
      performed on a limited range of substrates indicated that the reagent might be an
      effective method for the development of latent fingerprints despite the new
      reagent producing less intense fluorescence.

PMID- 14640273
TI  - Analysis and classification of common vegetable oils.
AB  - The analysis of fatty acids from common vegetable oils was investigated for
      application to forensic casework. A base-catalyzed transesterification of the
      fatty acids to fatty acid methyl esters using tetramethylammonium hydroxide was
      simple, rapid, straightforward and inexpensive. Canola, corn, olive, peanut,
      safflower, soybean and sunflower oils were able to be classified based on their
      fatty acid methyl ester profiles. Using gas chromatography-mass spectrometry, the
      detection limits for canola, corn, olive, peanut and safflower oils were
      determined to be 0.4 mg/mL or less and 0.2 mg/mL or less for soybean and
      sunflower oils.

PMID- 14640274
TI  - Time since discharge of shotgun shells.
AB  - A technique for the estimation of time since discharge of a given class of spent
      shotgun shells is presented. The technique involved the use of SPME (Solid Phase
      Microextraction) sampling from the atmosphere inside spent shotgun shells.
      Compounds absorbed on the SPME fiber were desorbed and analyzed with GC-MS. The
      decrease in concentration of the combustion product naphthalene was monitored in
      all shells over a two-month period. Three conditions were examined to prevent
      naphthalene from escaping prior to testing the shells. A glass vial was
      successfully incorporated to halt the dissipation of naphthalene. At room
      temperature the naphthalene peak can be measured for several months and the curve
      fitting data can lead to an estimation of time since discharge.

PMID- 14640275
TI  - Extraction and analysis of human nuclear and mitochondrial DNA from electron beam
      irradiated envelopes.
AB  - The United States Postal Service is considering methods such as electron beam
      irradiation to neutralize biological agents sent through the mail. While this is
      proven to reduce/eliminate pathogenic organisms, it may also degrade human
      genomic DNA and therefore hinder the ability to garner forensically informative
      genetic profiles. To determine the effects of electron beam irradiation on DNA
      typing, 16 white, standard letter-sized envelopes were licked. Half of the
      envelopes served as nonirradiated controls while the other half underwent
      irradiation at dosages sufficient to kill anthrax spores (29.3 and 51.6 kGy).
      Total cellular DNA was extracted from all envelopes; nuclear short tandem repeat
      loci, as well as the hypervariable region I from mitochondrial DNA, were
      amplified by means of the polymerase chain reaction. Short tandem repeat profiles
      and mitochondrial DNA sequence haplotypes were acquired on an ABI Prism 310
      Genetic Analyzer platform. Analysis of data from irradiated samples revealed
      evidence of DNA degradation; however, the ability to construct full genetic
      profiles from both nuclear and mitochondrial DNA remained largely unaffected. The
      use of the polymerase chain reaction, coupled with florescent fragment analysis
      and mitochondrial DNA sequencing, should be considered to profile biological
      material from evidence enduring irradiation to inactivate infectious agents.

PMID- 14640276
TI  - Higher failures of amelogenin sex test in an Indian population group.
AB  - The human sex test in forensic multiplexes is based on the amelogenin gene on
      both the X and Y chromosomes commonly used in sex genotyping. In this study of
      338 male individuals in a Malaysian population comprising Malays, Chinese and
      Indians, using the AmpFlSTR Profiler Plus kit, the amelogenin test gave a
      significant proportion of null alleles in the Indian ethnic group (3.6%
      frequency) and 0.88% frequency in the Malay ethnic group due to a deletion of the
      gene on the Y chromosome. This sex test also failed in a forensic casework
      sample. Failure of the amelogenin test highlights the need for more reliable sex
      determination than is offered by the amelogenin locus in the Malay and Indian
      populations. The gender of the Indian-Malay amelogenin nulls was confirmed by the
      presence of three Y-STR alleles (DYS438, DYS390 and DYS439). For the Indian
      ethnic group, one of the Y-STR forms a stable haplotype with the amelogenin null.
      The amelogenin-deletion individuals also showed a null with a male-specific
      minisatellite MSY1, indicating that a very large deletion was involved that
      included the amelogenin and the MSY1 loci on the short arm of the Y chromosomes
      (Yp).

PMID- 14640277
TI  - Enhancing contrast of fingerprints on plastic tape.
AB  - Many of the currently available fingerprinting methods have limited ability to
      visualize fingerprints on plastic tape without expensive equipment or significant
      handling of the sample. This is especially true for visualizing fingerprints on
      black electrical tape. This study sought a hands-off method to produce easy
      visualization of fingerprints on different types of plastic tape, including black
      electrical tape, without the need for expensive equipment. The methods selected
      were to sublime disperse dyes into the tape, both with and without the fuming of
      cyanoacrylate, everywhere except for where the fingerprint was applied. The
      resulting color contrasts provided enough differentiation to visualize
      fingerprints on plastic tape under ambient light. Sequential fuming with
      cyanoacrylate followed by disperse dyes provided the best visualizations on all
      tapes, and cyanoacrylate followed by disperse yellow 211 clearly visualized
      fingerprints on black electrical tape.

PMID- 14640279
TI  - Homemade battery-operated multi-barreled muzzle-loading gun.
AB  - In a recent shootout by a terrorist group against a law enforcement agency, some
      unusual firearms were seized. On examination, these firearms were found to be
      homemade, battery-operated, multi-barreled muzzle-loading guns, analogous to a
      repeater. Reference to battery-operated firearms is rather scanty in the
      literature. Hence, the unique design features, electrical circuit, and the
      operation system of these unusual guns are described.

PMID- 14640278
TI  - Using hydrophilic adhesive tape for collection of evidence for forensic DNA
      analysis.
AB  - Known exemplar samples of human DNA have traditionally been body fluids, such as
      blood, saliva, and semen. In each case, the presence of water is a risk for the
      bacterial growth, which may degrade the DNA evidence. In this study, the authors
      have developed a method that employed a hydrophilic adhesive tape (HAT) for
      collecting DNA evidence. The HAT method was used to remove surface cells from
      relatively hairless areas on the body. The area examined were ankle, arm, behind
      the ear, between fingers and back of the neck. The HAT was then dissolved in the
      extraction buffer. DNA typing was performed at vWA, THo1, F13A1, and FES loci
      using the short tandem repeat (STR) analysis. Our results show that the samples
      collected from ear give the best results with a success rate of 100%. All
      subjects tested by this method had known STR genotypes established from buccal
      swabs. The authors' results suggest that the HAT method can be used as a less
      invasive method for collecting biological evidence for forensic DNA analysis. In
      addition, this collection method should reduce the risk of DNA degradation due to
      the moisture, which is encountered using conventional collecting methods.

PMID- 14640280
TI  - The reliability of digitized radiographs for dental identification: a Web-based
      study.
AB  - In the era of Daubert and other judicial rulings pertaining to the acceptability
      of forensic evidence, it is increasingly important that experts are able to
      testify that their methods have been scientifically tested and that error rates
      and other factors relating to reliability have been published. The purpose of
      this study was to determine the reliability of digitized radiographic comparisons
      for the purposes of dental identification. Participants with various forensic
      backgrounds and experience levels were passively recruited to the website. Ten
      forensic identification cases composed of antemortem and postmortem dental
      radiographs were supplied to examiners using a bespoke website. Participants
      responded to the cases on two occasions after a one-month washout interval using
      the ABFO conclusion levels for forensic identifications. A total of 115 first
      attempts and 87 matched second attempts were received. Of the total responses,
      72% were dentally trained respondents who had completed at least one forensic
      identification case; of these, 38% were experienced forensic dentists who had
      completed more than 25 identifications. Data relating to accuracy, intra- and
      inter-examiner agreement, and the effect of case difficulty are presented. Mean
      accuracy was 85.5% for all cases, with the experienced forensic dentists
      obtaining a 91% success rate. The inter-examiner agreement on the negative
      identification cases was classified as poor. The data suggest that dental
      identifications resulting from the comparison of postmortem and antemortem
      radiographs are valid, accurate, and reliable when undertaken by experienced
      odontologists.

PMID- 14640281
TI  - The gander disaster: dental identification in a military tragedy.
AB  - The authors record the contributions of dentistry to the identification of
      victims of one of the most significant disasters in aviation and U.S. military
      history--the December 1985 crash of a DC-8 charter airliner near Gander,
      Newfoundland (now known as Newfoundland and Labrador), Canada, which killed 248
      Army personnel and 8 crewmembers. Most of the dental records of the military
      victims were destroyed in the crash, and, as a result, this loss hampered dental
      identification. Nevertheless, dental identification was the primary means of
      identification for many because a very high percentage of the bodies were
      severely burned and fragmented. Many phases of the U.S. identification efforts
      have been reported, but the dental-investigation aspects have been mentioned only
      in passing. Therefore, this article documents the dental team's organization,
      methodology, and a variety of remarkable problems that the team encountered.

PMID- 14640282
TI  - Forensic microradiology: micro-computed tomography (Micro-CT) and analysis of
      patterned injuries inside of bone.
AB  - When a knife is stabbed in bone, it leaves an impression in the bone. The
      characteristics (shape, size, etc.) may indicate the type of tool used to produce
      the patterned injury in bone. Until now it has been impossible in forensic
      sciences to document such damage precisely and non-destructively. Micro-computed
      tomography (Micro-CT) offers an opportunity to analyze patterned injuries of tool
      marks made in bone. Using high-resolution Micro-CT and computer software,
      detailed analysis of three-dimensional (3D) architecture has recently become
      feasible and allows microstructural 3D bone information to be collected. With
      adequate viewing software, data from 2D slice of an arbitrary plane can be
      extracted from 3D datasets. Using such software as a "digital virtual knife," the
      examiner can interactively section and analyze the 3D sample. Analysis of the
      bone injury revealed that Micro-CT provides an opportunity to correlate a bone
      injury to an injury-causing instrument. Even broken knife tips can be graphically
      and non-destructively assigned to a suspect weapon.

PMID- 14640283
TI  - Anal findings in sexual abuse of children (a descriptive study).
AB  - The aim of this study was to assess anal physical findings in children whose
      abuse was admitted by the perpetrator. Fifty children were studied in whom
      medical assessment took place remote in time from anal abuse which was admitted
      by the perpetrator. Medical assessment included examination to detect the
      presence of anal physical signs. Most frequent signs were anal scars and tags
      (either single or multiple) present, respectively, in 84 and 32% of cases. In
      some cases scars extended to the perianal region. Other signs included reflex
      anal dilatation (RAD) and venous congestion (VC) found, separately or associated
      with other signs, in over 33% of the cases. In 6% of the cases there were no
      abnormal anal findings. The results confirm earlier reports that physical signs,
      including scars, tags, RAD, funneled anus and extensive venous congestion, are
      often present in abused children, singly or in combination, and that anal
      examination should be undertaken even months after a known or suspected sexual
      assault. In the legal setting these physical signs are seen in association with
      anal abuse and support the child's statement. They do not per se provide proof of
      abuse.

PMID- 14640284
TI  - Virtopsy-postmortem multislice computed tomography (MSCT) and magnetic resonance
      imaging (MRI) in a fatal scuba diving incident.
AB  - The body of a 44-year-old scuba diver was examined using postmortem multislice
      computed tomography (MSCT) and magnetic resonance imaging (MRI), and findings
      were verified by subsequent autopsy. The goal was to find out whether the
      important pathomorphological findings for the reconstruction of events and the
      identification of cause and manner of death could be identified using modem
      digital cross-sectioning techniques. The findings of a massive vital
      decompression with pulmonary barotrauma and lethal gas embolism were identified
      in the radiological images. MSCT and MRI were superior to autopsy in the
      demonstration of the extent and distribution of gas accumulation in
      intraparenchymal blood vessels of internal organs as well as in areas of the body
      inaccessible by standard autopsy.

PMID- 14640285
TI  - 3D surface and body documentation in forensic medicine: 3-D/CAD Photogrammetry
      merged with 3D radiological scanning.
AB  - A main goal of forensic medicine is to document and to translate medical findings
      to a language and/or visualization that is readable and understandable for
      judicial persons and for medical laymen. Therefore, in addition to classical
      methods, scientific cutting-edge technologies can and should be used. Through the
      use of the Forensic, 3-D/CAD-supported Photogrammetric method the documentation
      of so-called "morphologic fingerprints" has been realized. Forensic, 3-D/CAD
      supported Photogrammetry creates morphologic data models of the injury and of the
      suspected injury-causing instrument allowing the evaluation of a match between
      the injury and the instrument. In addition to the photogrammetric body surface
      registration, the radiological documentation provided by a volume scan (i.e.,
      spiral, multi-detector CT, or MRI) registers the sub-surface injury, which is not
      visible to Photogrammetry. The new, combined method of merging Photogrammetry and
      Radiology data sets creates the potential to perform many kinds of
      reconstructions and postprocessing of (patterned) injuries in the realm of
      forensic medical case work. Using this merging method of colored photogrammetric
      surface and gray-scale radiological internal documentation, a great step towards
      a new kind of reality-based, high-tech wound documentation and visualization in
      forensic medicine is made. The combination of the methods of 3D/CAD
      Photogrammetry and Radiology has the advantage of being observer-independent, non
      subjective, non-invasive, digitally storable over years or decades and even
      transferable over the web for second opinion.

PMID- 14640286
TI  - Hyperextension and rotation of head causing internal carotid artery laceration
      with basilar subarachnoid hematoma.
AB  - Hyperextension of the head can cause injury to the vessels at the base of the
      brain. These lacerations are believed to be caused by stretching of the vessels
      due to the abrupt movement of the head and rotational acceleration of the brain
      within the cranium, and they usually occur in the intracranial portions of the
      vessels, producing a subarachnoid hemorrhage. This is the case of a 35-year-old
      man who received a blow to the face that forcefully hyperextended and rotated his
      head to the left. Autopsy revealed an intracranial right internal carotid
      laceration extending from a calcified atherosclerotic plaque. This unusual injury
      may be due to a combination of blunt force applied to the head and the alteration
      of the vessel's structural and functional capacities secondary to
      atherosclerosis.

PMID- 14640287
TI  - Meningitis following gunshot wound of the neck.
AB  - It is generally assumed that a missile fired from a gun is subjected to
      sufficient heat to render it sterilized. For this reason, retained bullets are
      not usually considered a source of infection. The infectious complications
      associated with gunshot wounds are typically attributed to perforation of a
      hollow viscus with leakage of gastrointestinal contents causing peritonitis or
      intra-abdominal abscess. There are several reports of bacterial meningitis
      involving the spinal cord in gunshot wounds that perforate the intestine prior to
      involving the thoracic or lumbar vertebral column; however, there are no
      published reports of cerebral meningitis resulting from a retained projectile in
      the spinal canal in which there was no injury to the gastrointestinal tract. This
      manuscript describes a woman who died as a result of unsuspected acute bacterial
      meningitis which developed secondary to a gunshot wound of the neck. The
      projectile fractured the first thoracic vertebra, lacerated the dura and contused
      the spinal cord at the C7-T1 junction. Meningitis developed at the C7-T1 level
      and ascended along the cervical spinal cord to the brain. The infection caused
      acute neurologic deterioration and death four days following the initial injury.

PMID- 14640288
TI  - Planned complex suicide by self-poisoning and a manipulated blank revolver:
      remarkable findings due to multiple gunshot wounds and self-made wooden
      projectiles.
AB  - A remarkable case of complex suicide with poisoning and multiple self-inflicted
      gunshot wounds to the head is reported. After ingestion of a liquid insecticide,
      the victim shot himself twice in the head, once in each temple. Self-manufactured
      wooden dowels were used as projectiles in combination with conventional blank
      cartridges. The dowels had been glued on top of the blank cartridges and expelled
      by propellant gases. Moreover, the blank revolver used had been extensively
      manipulated in a rarely observed manner. Several occlusive devices had been
      removed from the barrel and the cylinder chamber to enable the expulsion of the
      wooden projectiles. The investigation of the methods used and the circumstances
      found at the scene pointed towards a planned complex suicide. A remarkable case
      with unusual projectiles, i.e., wooden dowels, fired by an extensively
      manipulated blank gun is reported, emphasizing the importance of close
      collaboration between the police firearm laboratory and forensic pathology in
      practical casework.

PMID- 14640289
TI  - Brain amino acid abnormalities in liver disease--a postmortem study.
AB  - In a postmortem exploratory study, we examined whether specific amino acid
      abnormalities associated with liver diseases in vivo may also be detected in
      human brain samples obtained at clinical autopsies. The branched-chain amino
      acids (BCAA: valine, leucine, isoleucine) were decreased in the group of patients
      with liver diseases compared with the control group, whereas the aromatic amino
      acids (AAA: phenylalanine, tyrosine) were increased. However, the ranges
      overlapped significantly and were not statistically different. The molar ratio
      BCAA/AAA was determined to be 1.92 in the collection of patients with liver
      diseases compared with 2.27 in the control group. In patients with liver disease,
      ornithine concentrations in the brain appeared significantly decreased whereas
      glutamine was significantly increased. No significant difference was found in the
      brain concentrations of proline. Amino acid analysis may contribute to the
      understanding of pathophysiological mechanisms of liver disease, which are
      discussed, and may supplement the postmortem diagnosis.

PMID- 14640291
TI  - Writer identification using hand-printed and non-hand-printed questioned
      documents.
AB  - Several federal district court judges have recently referred to the purported
      lack of information on the proficiency of forensic document examiners (FDEs) in
      identifying writers of hand-printed documents. In order to provide the necessary
      information, we have re-analyzed data on writer identification that were
      collected in 1996 from 90 forensic document examiners and 34 laypersons. These
      data were used previously to assess the proficiency of FDEs using handwritten
      documents in several different types of writing. In the new analysis we separated
      data on hand-printed (HP) documents from data on non-hand-printed (NHP) documents
      and compiled error rates and statistics in each category. The main findings are:
      (1) whether or not the documents were hand-printed, the performance of FDEs was
      much better than that of laypersons; (2) statistical tests found no difference
      between the data provided by the FDEs in the HP and NHP categories; (3)
      statistical tests found no difference between the data provided by laypersons in
      the HP and NHP categories; and (4) statistical tests found differences between
      the data provided by the FDEs and the laypersons in both the HP and NHP
      categories. Similar results were obtained when hand-printed documents were
      compared to cursive documents and when cursive documents were compared to non
      cursive documents. All the evidence indicates that in our proficiency test the
      performance of FDEs in writer identification was much better than the performance
      of laypersons in each one of the following document categories: (1) hand-printed;
      (2) non-hand-printed; (3) cursive; and (4) non-cursive.

PMID- 14640290
TI  - A media violence-inspired juvenile sexual homicide offender 13 years later.
AB  - No follow-up studies exist on how minors who commit sexual homicides adjust once
      released back into the community. This is an important question given the extreme
      nature of their crimes, lack of recidivism data, and the expectation that one
      half of them will be freed from prison by mid-life. Likewise, no studies exist on
      the role our culture's pervasive media violence plays in these offenses. This
      report describes a 13-year-old boy who committed a witnessed media violence
      inspired sexual homicide. Follow-up information is provided on his community
      adjustment as an adult four years after release from prison. He had multiple
      indicators of brain dysfunction, and watched a "slasher" film just before
      committing the blitz style crime upon a female neighbor. Media violence
      literature is reviewed--against a backdrop of developmental abnormalities,
      neuropsychiatric vulnerabilities, family dysfunction, and mental illness. This
      case illustrates how the confluence of such variables, combined with the tinder
      of erotic screen violence, may lead to sexual murder.

PMID- 14640292
TI  - Color separation of signature and stamp inks to facilitate handwriting
      examination.
AB  - The questioned documents laboratory often encounters cases where handwriting that
      is to be examined intersects with some interfering factor such as a rubber stamp,
      typewriting or background printing. In these cases, line direction, beginning and
      ending features of letters and other fine details of the handwriting may be lost
      in the "noise" of the intersecting ink. The purpose of this paper is to show
      several new digital photography methods that may be used to "subtract" the effect
      of the intersecting ink, thereby enhancing that of the handwriting ink in order
      to enable the document examiner to conduct a complete examination. These methods
      have the advantage of being fast and do not involve the use of expensive material
      or equipment. Several new methods are described that may be used to separate the
      colors of the handwriting ink from that of the intersecting ink: the analog
      method and several digital methods such as RGB-HSB-CMYK, L*a*b color, and color
      separation using the Channel Mixer function of Adobe Photoshop. Successful
      application of these color separation methods to specific handwriting ink/rubber
      stamp ink color combinations shows that the effect of the intersecting ink may
      indeed be minimalized if not canceled altogether. Application of the suggested
      methods may well make the difference between a nonconclusive handwriting
      examination and a full analysis of the questioned handwriting.

PMID- 14640293
TI  - Pharmacogenomics as an aspect of molecular autopsy for forensic
      pathology/toxicology: does genotyping CYP 2D6 serve as an adjunct for certifying
      methadone toxicity?
AB  - Pharmacogenomics, applied as an aspect of molecular autopsy, may be used as an
      adjunct for certifying methadone fatalities. Methadone is metabolized by
      cytochrome P-450 (CYP) 1A2, 3A4, and 2D6. We hypothesized that methadone toxicity
      may be partially due to CYP 2D6 *3, *4, and *5 variant alleles, resulting in poor
      drug metabolism. A retrospective analysis was performed on covariables and risk
      factors of 21 methadone cases from the Milwaukee County Medical Examiner's Office
      (1998-2000). PCR genotyping showed: one heterozygous for 2D6*3, two homozygous
      for 2D6*4, five heterozygous for 2D6*4, and one heterozygous for both 2D6*3 and
      *4. This limited number of cases showed that the prevalence of poor metabolizer
      was higher but not significantly different from that of a control group (n = 23)
      (P > 0.05, Fisher Exact Test). Thus, CYP 2D6 mutations may not yet be directly
      associated with methadone toxicity. However, pharmacogenomics, complementing
      other case findings, served as an adjunct in interpreting methadone toxicity of
      poor and intermediate metabolizers.

PMID- 14640294
TI  - Coexistence and concentrations of ethanol and diazepam in postmortem blood
      specimens: risk for enhanced toxicity?
AB  - Both ethanol and diazepam are classified as depressants of the central nervous
      system and exert their effects via the GABAA receptor complex. We report the
      coexistence and concentrations of ethanol, diazepam, and its primary metabolite
      nordiazepam in a case series of 234 forensic autopsies collected over a ten-year
      period. Diazepam, nordiazepam, and ethanol were determined in femoral venous
      blood by highly selective gas chromatographic methods. The mean (median) femoral
      blood concentrations were ethanol 0.24 g/100 mL (0.25 g/100 mL), diazepam (D)
      0.23 microg/g (0.10 microg/g), nordiazepam (ND) 0.24 micro/g (0.20 microg/g), sum
      (D + ND) 0.43 microg/g (0.30 microg/g), and the ratio D/ND was 1.19 (1.0). When
      cause of death was attributed to alcohol and/or drug intoxication (N = 50), the
      mean and median blood-ethanol concentration was higher, being 0.36 g/100 mL and
      0.38 g/100 mL, respectively, whereas the mean (median) and range of blood
      diazepam concentrations were about the same, 0.23 microg/g (0.10 microg/g) and
      0.05 to 1.2 microg/g. The femoral-blood concentrations of diazepam and
      nordiazepam were highly correlated (r = 0.73), but there was no correlation
      between the concentrations of ethanol and diazepam (r = -0.15). In another 114
      fatalities (all causes of death) with diazepam and/or nordiazepam as the only
      drugs present, the mean (median) and range of blood-diazepam concentrations were
      0.22 microg/g (0.10 microg/g) and 0.03 to 3.5 microg/g. The pathologists report
      showed that none of these deaths were classed as drug intoxications. The
      impression gleaned from this study of ethanol-diazepam deaths is that high blood
      ethanol concentration is the major causative factor. We found no evidence that
      concurrent use of diazepam enhanced the acute toxicity of ethanol, although
      interpretation is complicated by the high blood-ethanol concentration (median
      0.38 g/100 mL), making it difficult to discern an added effect of diazepam.

PMID- 14640295
TI  - Distribution of HUMACTBP2 (SE33) alleles in three North American populations.

PMID- 14640296
TI  - Population data of ABO gene applicable to human identification in Koreans.

PMID- 14640297
TI  - HLA-DQA1 and polymarker in the Uros population from Peruvian Highland.

PMID- 14640298
TI  - Population data of three X-chromosomal STRs: DXS7132, DXS7133 and GATA172D05 in
      North Italy.

PMID- 14640299
TI  - Allele diversities and haplotypes of two novel Y-STR in a Chinese population.

PMID- 14640300
TI  - Y-chromosome STR haplotypes in a Han ethnic group of Chinese population.

PMID- 14640301
TI  - Allele frequencies of four short tandem repeat loci in Chinese Han population.

PMID- 14640302
TI  - Commentary on: Wu AHB, Bellantoni NF. Stability of choleslerol gall stones after
      165 years of burial. J Forensic Sci 2003;48(3):633-634.

PMID- 14640303
TI  - Toward an understanding of developmental coordination disorder: terminological
      and diagnostic issues.
AB  - Awareness of children who experience unexpected difficulty in the acquisition of
      motor skills has increased dramatically over the last twenty years. Although the
      positing of a distinct syndrome has proven seminal in provoking further
      questions, several basic terminological problems remain unresolved. In this
      paper, we conduct a component analysis of the three, principal competing labels
      for this disorder, two of them being elements derived from systematic diagnostic
      frameworks. Our preference for the DSM IV term Developmental Coordination
      Disorder (DCD) is stated and justified. Problems in diagnosis are discussed,
      especially in relation to the etiology-dominated medical model. We argue that an
      attempt should be made to identify (pathological) positive signs that can
      reliably be detected rather than relying entirely on normative evidence of a lack
      of skills exhibited by other children of the same age. The high degree of overlap
      between DCD and other developmental disorders suggests that DCD might not
      constitute a distinct syndrome. In this context, we emphasize the need to
      determine whether incoordination takes a different form when it occurs alone or
      whether it is combined with general developmental delay or with other specific
      disorders in children of normal intelligence.

PMID- 14640304
TI  - Development of action and the clinical continuum.
AB  - The development of action is depicted as consisting of changes in the task
      specific couplings between perception, movement, and posture. It is argued that
      this approach may provide a much needed basis from which attempts can be made at
      theoretically unifying the constituents of the clinical continuum (viz., early
      detection, diagnosis, prognosis, and intervention). Illustrative examples germane
      to this approach are given with regard to how posture serves as a constraint on
      the emergence of reaching movements and how cortical development influences the
      coordination of leg movements as revealed by a study involving infants with white
      matter lesions. Particular attention is paid to early detection and it is
      recommended that further improvements to this aspect of the clinical continuum
      can be derived from combining serial qualitative and quantitative (kinematic)
      assessments with brain-imaging techniques. It is emphasized that quantitative
      assessments should incorporate experimental manipulations of perception, movement
      or posture during transitional periods in development. Concluding comments
      include consideration of the timing of early intervention.

PMID- 14640305
TI  - Perceptual deficits in clumsy children: inter- and intra-modal matching approach-
      a window into clumsy behavior.
AB  - This article will focus on the underlying perceptual deficits that might lead to
      inadequacies in motor performance in children. Two lines of enquiry have
      dominated the literature: visual-perceptual deficit and/or visual-motor deficits
      and proprioceptive deficits. The theoretical and methodological shortcomings in
      these approaches are discussed. Then attention is primarily directed toward the
      concept of inter- and intra-modal matching (sensory integration), particularly
      with respect to vision and proprioception, an ability deemed to underlie many
      real-life motor skills. Such an approach allows parallels to be drawn between
      behavioral manifestations of motor impairment and potential underlying
      neurological information-processing disorders, particularly as these relate to
      hemispheric competence.

PMID- 14640306
TI  - Developmental coordination disorder: is clumsy motor behavior caused by a lesion
      of the brain at early age?
AB  - Children presenting with Developmental Coordination Disorder or clumsiness often
      exhibit signs of minor neurological dysfunction (MND). The data of the Groningen
      Perinatal Project, a long-term follow-up project on the relations between
      prenatal and perinatal adversities and neurological, behavioral, and cognitive
      development revealed that two basic forms of MND can be distinguished: simple and
      complex MND. During school age children with simple MND are characterized by the
      presence of one or two dysfunctional clusters of MND, in adolescence by the
      presence of choreiform dyskinesia or hypotonia. Probably the major sources of
      origin of simple MND are genetic constitution and stress during early life.
      Simple MND might reflect the lower tail of the normal distribution of the quality
      of non-pathological brain function. In line with this hypothesis is the finding
      that simple MND is associatedwith only a moderately increased risk for learning-
      and behavioral problems. Children with complex MND present at school age with at
      least three dysfunctional clusters of MND, in adolescence with problems in fine
      manipulation or coordination. Perinatal adversities play an evident etiological
      role in the development of complex MND, suggesting that it might be attributed to
      a lesion of the brain at early age. In line with this idea is the finding that
      complex MND shows a strong correlation with attention and learning problems.

PMID- 14640307
TI  - Neonatal brain MRI and motor outcome at school age in children with neonatal
      encephalopathy: a review of personal experience.
AB  - The aim of this paper is to review (i) the spectrum of neuromotor function at
      school age in children who had been born full-term and presented with neonatal
      encephalopathy (NE) and low Apgar scores and (ii) the relation between the
      presence/absence of such difficulties and neonatal brain MRI. Motor outcome
      appears to be mainly related to the severity of basal ganglia and internal
      capsule involvement. Severe basal ganglia lesions were always associated with the
      most severe outcome, microcephaly, tetraplegia, and severe global delay, whereas
      more discrete basal ganglia lesions were associated with athetoid cerebral palsy,
      with normal cognitive development, or minor neuro-motor abnormalities. White
      matter lesions were associated with abnormal motor outcome only if the internal
      capsule was involved. Children with moderate white matter changes but normal
      internal capsule had normal motor outcome at school age.

PMID- 14640308
TI  - Why bother about clumsiness? The implications of having developmental
      coordination disorder (DCD).
AB  - Developmental coordination disorder (DCD) is a common motor problem affecting-
      even in rather severe form--several percent of school age children. In the past,
      DCD has usually been called 'clumsy child syndrome' or 'non-cerebral-palsy motor
      perception dysfunction'. This disorder is more common in boys than in girls and
      is very often associated with psychopathology, particularly with attention
      deficit/hyperactivity disorder (ADHD) and autism spectrum disorders/ autistic
      type problems. Conversely, children with ADHD and autism spectrum problems,
      particularly those given a diagnosis of Asperger syndrome, have a very high rate
      of comorbid DCD. Psychiatrists appear to be unaware of this type of comorbidity
      in their young patients. Neurologists, on the other hand, usually pay little
      attention to the striking behavioral and emotional problems shown by so many of
      their 'clumsy' patients. A need exists for a much clearer focus on DCD-in child
      psychiatry and in child neurology-both in research and in clinical practice.

PMID- 14640309
TI  - Principles of force gradation in skeletal muscles.
AB  - A brief survey is given of how motoneurons and motor units are used for the
      gradation of muscle force during motor behavior. Basic properties of motoneurons
      and muscle fibers, including major kinds of functional specialization along the
      axis of 'fast' vs. 'slow', are reviewed. The principles underlying the rate and
      recruitment gradation of force are described, stressing that the properties of
      motoneurons and muscle fibers are matched to automate important aspects of the
      gradation procedure. Recent investigations concerning synaptically evoked changes
      in the discharge properties of motoneurons receive special attention, including
      'plateau' currents and, under appropriate conditions, self-sustained 'plateau'
      discharges.

PMID- 14640310
TI  - Complete and partial lesions of the pyramidal tract in the rat affect qualitative
      measures of skilled movements: impairment in fixations as a model for clumsy
      behavior.
AB  - Little is known about prenatal and perinatal brain injury resulting in subsequent
      clumsy behavior in children. One candidate motor system is the pyramidal tract.
      The tract traverses the entire central nervous system and, through direct and
      indirect connections to the brainstem and spinal cord sensory and motor nuclei,
      is involved in the learning and execution of skilled movements. Here, rats,
      either naive or pretrained on a number of motor tasks, were assessed for acute
      and chronic impairments following complete or incomplete pyramidal tract lesions.
      Postsurgery rats with complete lesions were impaired on the qualitative measures
      of limb aiming, supination, and posture. Impaired movements require fixations,
      complementary movements in different body segments. The impairment in fixations
      was manifest acutely and underwent no improvement with subsequent
      training/testing. The finding that complete and partial pyramidal tract lesions
      produce chronic impairment in fixations provides insight for understanding clumsy
      behavior in humans and its potential remediation via specific training in making
      fixations.

PMID- 14640311
TI  - Development and plasticity of the corticospinal system in man.

PMID- 14640312
TI  - The basal ganglia and motor control.
AB  - This paper briefly reviews the functional anatomy of the basal ganglia and their
      relationships with the thalamocortical system. The basal ganglia, including the
      striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a
      number of parallel, functionally segregated cortical-subcortical circuits. These
      circuits support a wide range of sensorimotor, cognitive and emotional
      motivational brain functions. A main role of the basal ganglia is the learning
      and selection of the most appropriate motor or behavioral programs. The internal
      functional organization of the basal ganglia is very well suited for such
      selection mechanisms, both in development and in adulthood. The question of
      whether clumsiness may be, at least in part, attributed to dysfunction of the
      basal ganglia is discussed in the context of the differential, complementary, or
      interactive roles of the basal ganglia and the cerebellum in the development of
      motor control.

PMID- 14640313
TI  - Reward processing in the brain: a prerequisite for movement preparation?
AB  - In the last decade, expanding animal studies on the cerebral organization of
      reward processing toward human in vivo situations has become possible. In this
      review, we define some of the concepts associated with reward, summarize the
      crucial importance of the dopaminergic system, and discuss the currently
      available neuroimaging studies in man. We will show that abstract concepts of
      human behavior like emotions, drive, arousal, and reinforcement are now open for
      further exploration in man at the level of neuronal circuit organization. The
      cerebral dopaminergic neurotransmitter circuitry does play an important role in
      the organization of both the motor and motivational system.

PMID- 14640314
TI  - Clumsiness and disturbed cerebellar development: insights from animal
      experiments.
AB  - Cerebellar functioning has been implied in the fine adjustments of muscle tone,
      in the coordination and the feed-forward control of movements and posture, as
      well as in the establishment and performance of motor skills. The cerebellar
      cortex in mammals develops late in neuro-ontogeny and an extrapolation from
      experimental results indicates that in the human the proliferation of the granule
      cells and the development of circuitry in the cerebellar cortex starts only in
      the last trimester of pregnancy and lasts until beyond the first birthday. This
      late development makes the cerebellar development particularly vulnerable to
      situations like an insufficient supply of nutrients, which may follow placental
      dysfunction, or to side effects of pharmacological treatments like the
      administration of corticosteroids in the postnatal period. We studied whether
      such situations might also lead to motor impairments. In rats, the effects of
      undernutrition during the brain growth spurt were investigated as well as those
      of corticosteroids administered in a period that is analogous to the 7th to 8th
      month of pregnancy in the human. Both these interferences affect cerebellar
      development and our results in rats indicate that they also lead to retardations
      in the emergence of certain reflexes, as well as to longer lasting motor
      impairments during locomotion. Extrapolation of these results strongly suggests
      that a disturbed cerebellar development should be considered as an important
      etiological factor in clumsiness in human children.

PMID- 14640315
TI  - Cerebellar involvement in clumsiness and other developmental disorders.
AB  - Cerebellar abnormalities have been linked to a number of developmental disorders.
      Much evidence is based on the analysis of high-resolution MRI scans. Imaging and
      behavioral studies have led researchers to consider functional contributions of
      the cerebellum beyond that associated with motor control. I review this
      literature, providing an analysis of different ways to consider the relation
      between cerebellar abnormalities and developmental disorders. Interestingly,
      although clumsiness is a problem of coordination, the contribution of cerebellar
      dysfunction to this developmental problem has received little attention. Select
      studies indicate that some clumsy children have difficulties on tasks requiring
      precise timing, similar to that observed in adult patients with cerebellar
      lesions. I suggest that the underlying neural bases of clumsiness are
      heterogeneous, with cerebellar dysfunction likely a major contributor for a
      subpopulation of such children.

PMID- 14640316
TI  - Effectiveness of neuromotor task training for children with developmental
      coordination disorder: a pilot study.
AB  - The aim of this pilot study was to evaluate the effectiveness of a Neuromotor
      Task Training (NTT), recently developed for the treatment of children with
      Developmental Coordination Disorder (DCD) by pediatric physical therapists in the
      Netherlands. NTT is a task-oriented treatment program based upon recent insights
      from motor control and motor learning research. Ten children with DCD
      (intervention group) were tested before and after 9 and 18 treatment sessions on
      the Movement ABC and a dysgraphia scale in order to measure the effectiveness of
      treatment on gross and fine motor skills in general and handwriting in
      particular. Five children (no-treatment control group) were tested twice with a
      time lag of nine weeks on the Movement ABC in order to measure spontaneous
      improvement. No improvement was measured for the children in the no-treatment
      control group, whereas a significant improvement was found for children in the
      intervention group for both quality of handwriting and performance on the
      Movement ABC after 18 treatment sessions.

PMID- 14640317
TI  - Discussion: significance and treatment of clumsiness in children.

PMID- 14640318
TI  - The human amygdala: an evolved system for relevance detection.
AB  - Evidence from pioneering animal research has suggested that the amygdala is
      involved in the processing of aversive stimuli, particularly fear-related
      information. Fear is central in the evolution of the mammalian brain: it is
      automatically and rapidly elicited by potentially dangerous and deadly events.
      The view that the amygdala shares the main characteristics of modular systems,
      e.g. domain specificity, automaticity, and cognitive impenetrability, has become
      popular in neuroscience. Because of its computational properties, it has been
      proposed to implement a rapid-response 'fear module'. In this article, we review
      recent patient and neuroimaging data of the human brain and argue that the
      fundamental criteria for the amygdala to be a modular system are not met. We
      propose a different computational view and suggest the notion of a specific
      involvement of the human amygdala in the appraisal of relevant events that
      include, but are not restricted to, fear-related stimuli. Considering the
      amygdala as a 'relevance detector' would integrate the 'fear module' hypothesis
      with the concept of an evolved neural system devoted to the processing of a
      broader category of biologically relevant stimuli. In primates, socially relevant
      events appear to have become, through evolution, the dominant elements of the
      amygdala's domain of specificity.

PMID- 14640320
TI  - Non-pharmacological interventions in cognitively impaired and demented patients-
      a comparison with cholinesterase inhibitors.
AB  - The present paper reviews studies examining the effects of non-pharmacological
      stimulation, i.e. bright light, physical activity and tactile stimulation
      (touch), on cognition, affective behaviour, and the sleep-wake rhythm of impaired
      and demented elderly, both in a qualitative (narrative) and quantitative (meta
      analytic) manner. An extensive search through eight bibliographic data bases
      (PubMed, Web of Science, ERIC, PsychINFO, Psyndex, Cinahl, Biological Abstracts
      and Rehabdata) was performed up to August 2002. The primary criterion for
      inclusion in this review was that studies provided sufficient data to calculate
      effect-sizes. In the qualitative analysis, all three types of stimulation
      appeared to improve cognitive functioning. Disturbances in behaviour react
      positively to bright light and tactile stimulation. Bright light was also
      beneficial to sleep. Tactile stimulation had, moreover, a beneficial influence on
      the patient-caretaker relationship. A comparison was made with several
      representative papers published since 1991 on the effects of acetylcholinesterase
      inhibitors on cognition and behaviour with representative papers on non
      pharmacological stimulation interventions. Data indicated that improvements in
      cognition and affective behaviour by non-pharmacological interventions (d' =
      0.32) and by cholinesterase inhibitors (d' = 0.31) were of similar effect-size.
      Possible mechanisms underlying the non-pharmacological stimulation effects are
      discussed and suggestions offered for future research.

PMID- 14640319
TI  - Genetic programming by the proteolytic fragments of the amyloid precursor
      protein: somewhere between confusion and clarity.
AB  - Mice engineered to overexpress disease-causing mutant amyloid precursor proteins
      (APP) display plaque deposition, but lack the hyperphosphorylated tau and massive
      neuronal loss characteristic of Alzheimer's disease (AD). Global gene expression
      profiles of brain regions from AD patients show upregulation of proapoptotic and
      inflammatory genes and down-regulation of neurotrophic, MAPK, phosphatase, and
      synaptic genes, while a profile of mice overexpressing a mutant APP shows the
      opposite trends in apoptotic and neurotrophic genes. The proteolytic fragments of
      the amyloid precursor protein have distinct biological actions. Both the gamma
      secretase cleaved COOH-terminal fragment (CTFgamma) and the alpha-secretase
      cleaved NH2-terminal of APP (sAPPalpha) can regulate gene expression. While Abeta
      and CTFgamma can lead to toxicity and cell death, sAPPalpha promotes neurite
      outgrowth, enhances memory, and protects against a variety of insults, including
      Abeta toxicity. In AD, Abeta levels increase while sAPPalpha levels decrease.
      These subtleties in the levels of APP cleavage products are not reproduced in
      mice overexpressing mutant APP. In fact, the gene expression changes driven by
      sAPPalpha, such as increases in transthyretin and insulin-like growth factor 2,
      may protect these mice from high levels of Abeta.

PMID- 14640321
TI  - Neurobehavioral characteristics of mice with modified intermediate filament
      genes.
AB  - Intermediate proteins comprise cytoskeletal elements that preserve the shape and
      structure of neurons. These proteins have been proposed to be involved in the
      onset and progression of amyotrophic lateral sclerosis (ALS), mainly
      characterized by motoneuron atrophy and paresis. In support of this hypothesis
      are the findings that genetically modified mice for intermediate filaments
      successfully mimic certain neuropathological aspects of ALS, such as reduced
      axonal caliber and retarded conduction speed in peripheral nerves, although often
      without leading to paresis. Nevertheless, even in those models with no overt
      phenotype, the involvement of intermediate proteins in motor function is
      underlined by the deficits in tests of balance and equilibrium revealed in mice
      containing transgenes for neurofilament of heavy molecular weight (NFH), alpha
      internexin, peripherin, and vimentin. In addition, spatial learning was impaired
      in transgenic mice expressing transgenes for NFH and NFM, similar to the memory
      deficits reported in patients with ALS.

PMID- 14640323
TI  - Plans approved for unified practice standards.

PMID- 14640324
TI  - Keeping in touch with the issues.

PMID- 14640322
TI  - Internal simulation of expected sensory experiences before movements get started.
AB  - The functions of the cortical and subcortical motor areas have been regarded as
      the execution and control of limb movements. We introduce recent neuroimaging
      evidence in humans that somatic sensation elicited by afferent inputs that signal
      limb movement also engage the motor areas. It is generally understood that
      somatic sensation can only be experienced once movement has been executed. Here
      we provide evidence that somatic sensation of limb movement can be internally
      simulated before the movement gets started by recruiting the motor areas. It is
      suggested that the sensory experiences that are expected when movements are
      actually executed can be internally simulated in the network of the motor areas
      during motor imagery.

PMID- 14640325
TI  - Study of factors that may predispose domestic cats to road traffic accidents:
      Part 2.
AB  - Between March 2000 and February 2001, six veterinary practices in Cambridgeshire
      collected data on 117 owned cats which they had examined after a road traffic
      accident (RTA). The owners of 66 of these cats completed questionnaires and the
      information in them was compared with the information in questionnaires from a
      control population of 796 cats that had never been in a road accident. The RTA
      cats were, on average, younger than the controls; when adjusted for age the two
      populations did not differ with respect to the time they spent outdoors or the
      time they had lived at their current address. Proportionately more of the RTA
      cats wore reflective collars and/or lived in areas with higher levels of traffic
      than the controls. The accidents were evenly distributed throughout the year, and
      there was a trend for more accidents to happen during the night than the day.
      Forty-eight per cent of the accidents whose location was known occurred just
      outside or very near the cat's home.

PMID- 14640326
TI  - Evaluation of tetracycline, erythromycin, penicillin and streptomycin for
      decontaminating koala semen contaminated in vitro with chlamydiae.
AB  - Semen from seven koalas was extended in a tris-citrate glucose diluent containing
      one of four antibiotics at different concentrations and then contaminated with a
      standard concentration of chlamydiae. These semen preparations were then tested
      for residual chlamydial viability by an in vitro cell culture assay, and any
      detrimental effect of the antibiotics on the motility and viability of the sperm
      was assessed. Penicillin at 25 iu/ml or more, erythromycin at 1000 microg/ml or
      more and tetracycline at 200 microg/ml or more were highly effective at rendering
      the chlamydiae non-viable, but streptomycin showed no antichlamydial activity.
      There was a significant reduction of the motility of spermatozoa extended in
      diluents containing erythromycin (P < 0.05), but spermatozoa incubated with
      tetracycline up to concentrations of 200 microg/ml were not affected.

PMID- 14640327
TI  - Serological study of a population of alpine chamois (Rupicapra r rupicapra)
      affected by an outbreak of respiratory disease.
AB  - A serological survey of respiratory virus infections was carried out from 1998 to
      2001 in Lecco province, Italy, as part of a health monitoring programme in a
      population of alpine chamois, many of which died of pneumonia in autumn and
      winter 2000 to 2001; 194 carcases of all age classes were found over a short
      period and in a small area. Eighteen of them, which were examined postmortem,
      consistently showed signs of severe fibrinous lobar pneumonia or catarrhal
      bronchopneumonia. Samples of serum from 145 chamois collected from hunted animals
      and carcases were tested by a virus neutralisation test against bovine
      respiratory syncytial virus (BRSV), bovine viral diarrhoea virus, bovine
      herpesvirus type 1 and parainfluenzavirus type 3. Positive results were detected
      only for BRSV. The area was divided into two subunits on the basis of the
      distribution of deaths; in the areas where fatalities were observed there was a
      significant increase of BRSV titres at the beginning of the outbreak.
      Furthermore, during the 2000 and 2001 hunting seasons antibody titres to BRSV
      were significantly higher in the areas where mortality occurred. The roe deer
      living in the same area were not affected by pneumonia and had a low prevalence
      of titres to BRSV which did not vary during the period of the study.

PMID- 14640328
TI  - Complete clinical recovery of a pony with histologically confirmed chronic grass
      sickness.

PMID- 14640329
TI  - Bovine spinal anomaly with anatomical similarities to complex vertebral
      malformation.

PMID- 14640330
TI  - Myiasis in two Hermann's tortoises (Testudo hermanni).

PMID- 14640331
TI  - Multiresistant nematodes on a Devon farm.

PMID- 14640332
TI  - Electric shock collars and dog training.

PMID- 14640333
TI  - Electric shock collars and dog training.

PMID- 14640334
TI  - Equine passports.

PMID- 14640335
TI  - What have we learned from OxyContin?

PMID- 14640336
TI  - Lawful prescribing and the prevention of diversion.
AB  - Concern about controlled substance diversion and overview of prescribers by legal
      and regulatory officials is growing. The article is designed to increase health
      professionals' awareness of the methods of diversion and to provide guidance on
      how diversion can be foiled. This paper also should help healthcare practitioners
      to better understand the regulations governing prescribing of controlled
      substances. Examples of unlawful prescribing of controlled substances are
      presented. Some behaviors of persons illegitimately seeking controlled substances
      from prescribers are described. Strategies to lessen the possibility of
      prescriptions being altered are discussed. Federal and state laws and regulations
      pertaining to controlled substances are described.

PMID- 14640337
TI  - Addiction, physical dependence, and tolerance: precise definitions to help
      clinicians evaluate and treat chronic pain patients.
AB  - Pain is among the most common complaints for which people seek medical care; yet
      pain is also among the most undertreated patient complaints. Reasons for this
      include reluctance by clinicians to prescribe and support the use of opioids,
      often due to a fear of addiction. To address this issue, three major health
      professional organizations that deal with the treatment of pain and addiction,
      the American Academy of Pain Medicine, the American Pain Society, and the
      American Society of Addiction Medicine, formed the Liaison Committee on Pain and
      Addiction (LCPA). The first mission of the LCPA was to formulate precise
      definitions of the terms addiction, physical dependence, and tolerance. This
      report explains these definitions and discusses how they apply to clinical
      practice.

PMID- 14640338
TI  - The International Association for Hospice and Palliative Care: international
      activities and future initiatives.
AB  - The International Association for Hospice and Palliative Care (IAHPC) is a global
      organization dedicated to the development and improvement of palliative care. The
      mission of IAHPC is to increase the availability and access to high quality
      hospice and palliative care for patients and families throughout the world. It
      does this by promoting communication, facilitating and providing education, and
      by becoming an information resource for patients, professionals, health care
      providers and policy makers around the world. This report describes activities of
      the IAHPC throughout the word and planned future initiatives.

PMID- 14640339
TI  - Symptom-related research from the agency for healthcare research and quality.
AB  - Recent reports on research supported by the Agency for Healthcare Research and
      Quality are summarized. These reports relate to use of aspirin for
      cardioprotection by patients taking NSAIDs, end of life care for nursing home
      residents with advanced directives, Cancer Patients' Satisfaction With Primary
      Care Pain Management, the need for increased medical training about adverse drug
      events, and dorsal root entry zone lesioning for central neuropathic pain. The
      research summarized in this report was abstracted from the AHRQ Research
      Activities.

PMID- 14640340
TI  - Symptomatic hyponatremia in patients on oxcarbazepine therapy for the treatment
      of neuropathic pain: two case reports.
AB  - Oxcarbazepine is an FDA approved anticonvulsant medication that has also been
      used clinically as a treatment for chronic neuropathic pain. Hyponatremia is
      occasionally seen with the older anticonvulsant carbamazepine, and oxcarbazepine
      is a derivative of that older drug. Two cases of hyponatremia associated with
      oxcarbazepine are reported and suggestions for monitoring for and managing this
      effect are provided.

PMID- 14640341
TI  - COX-2 selective NSAIDs and advancing legal issues in palliative care.
AB  - The role of the cycloxygenase-2 selective NSAIDs in palliative care has not been
      studied, per se, but the improved adverse gastrointestinal and platelet effect
      profiles of these newer agents over nonselective NSAIDs offers potential
      advantages in patients with advanced disease. These issues are discussed. The
      need for greater emphasis on scientific and evidence-based approaches to
      palliative care is great and generally recognized in the clinical and scientific
      communities. Recent legal opinions about aggressive care of patients approaching
      end of life has increased this need. The clinical and ethical implications of
      these decisions are discussed.

PMID- 14640342
TI  - Cost-of-illness studies.
AB  - Cost-of-illness studies measure the overall economic impact of a disease on
      society. Such studies are important in setting public health priorities and for
      economic evaluation of new treatments. These studies should take the societal
      perspective and include both direct and indirect costs. Often indirect costs
      exceed direct costs. Comparison of cost-of-illness studies from different
      countries is difficult because of differences in population, currency, the way
      health care is provided, and other social and political factors.

PMID- 14640343
TI  - Pain and palliative care in The Cochrane Library: Issue Number 3 for 2002.
AB  - The Cochrane Library of systematic reviews is published quarterly. Six of the 62
      new reviews published in Issue 4 for 2001 in February 2002 are relevant to pain
      and palliative care. Annotated bibliographies for those nine reviews are
      provided.

PMID- 14640344
TI  - Pain scales don't weigh every risk.
AB  - The risk of patients receiving opioids without adequate monitoring and resulting
      in adverse outcomes has been noted by the Institute for Safe Medication
      Practices. More aggressive opioid analgesia often is clinically indicated, but it
      is not without risk. Adverse drug events due to opioids have increased with the
      recent adoption of pain management standards by the Joint Commission on
      Accreditation of Healthcare Organizations. The implications of this are discussed
      and a specific safe practice recommendation is provided.

PMID- 14640345
TI  - Calls for improved cancer symptom control... and some responses.
AB  - The hospice movement and palliative care programs have grown over the past
      quarter century at an astounding rate. Such programs now treat far more than just
      pain or cancer. Nevertheless, recognition of the critical need for improved
      cancer pain management was the genesis of modern palliative care. However, even
      today, many Americans lack ready access to such care. Recently, an increased
      focus on the need for more and better palliative care has led to important new
      publications, federal funding initiatives from palliative care research, and
      explicit recommendations from the National Cancer Policy Board on ways to lessen
      barriers to palliative care. Some of these potential solutions are discussed.

PMID- 14640347
TI  - Compliance Policy Guide on Chapter 4 Human Drugs: Section 460.200 Pharmacy
      Compounding.

PMID- 14640346
TI  - Symptom management in cancer: pain, depression and fatigue: State-of-the-Science
      Conference Statement.
AB  - NIH Consensus Statements are prepared by a nonadvocate, non-Federal panel of
      experts, based on (1) presentations by investigators working in areas relevant to
      the consensus questions during a 2 day public session; (2) questions and
      statements from conference attendees during open discussion periods that are part
      of the public session; and (3) closed deliberations by the panel during the
      remainder of the second day and morning of the third. This statement is an
      independent report of the panel and is not a policy statement of the NIH or the
      Federal Government. The statement reflects the panel's assessment of medical
      knowledge available at the time the statement was written. Thus, it provides a
      "snapshot in time" of the state of knowledge on the conference topic. When
      reading the statement, keep in mind that new knowledge is inevitably accumulating
      through medical research.

PMID- 14640348
TI  - Possible association between methadone and potentially fatal cardiac arrhythmia.

PMID- 14640349
TI  - Joint commission announces national patient safety goals.

PMID- 14640350
TI  - NIH to fund pediatric palliative care research.

PMID- 14640351
TI  - Why we need outcomes research and pharmacoeconomics in pain management and
      palliative care.

PMID- 14640352
TI  - Opioid treatment of chronic pain in patients with addiction.
AB  - Patients with a history of drug or alcohol addiction may present to physicians
      with pain complaints. The medical literature is weak on the treatment of pain
      with opioids in patients in recovery or active addiction. This is because
      inconsistent criteria were used to define addiction and the types of chronic
      pain. There are clear differences between physical dependence, tolerance, and
      addiction. Addiction is different from pseudoaddiction and must be determined by
      the patient's behavior after appropriate pain management. Long-acting opioids are
      often the medications of choice for moderate to severe pain control. Short-acting
      opioids can be used for breakthrough pain. There are many other medications that
      can enhance pain control as adjunctive analgesics. Drug-seeking behavior may be
      seen with either active addiction or pseudoaddiction, or as part of deviant
      behavior such as drug diversion. A way to distinguish between these conditions is
      by giving the patient appropriate pain medication and observing the pattern of
      behavior to determine which is causing the drug-seeking behavior. Safe
      prescribing of medications with abuse potential includes use of a medication
      agreement, setting goals with the patient, giving appropriate amounts of pain
      medication, monitoring with pill counts and drug screens, and careful
      documentation. Even patients with a history of addiction can benefit from opioid
      pain medications if monitored appropriately.

PMID- 14640353
TI  - Ketamine as an analgesic: parenteral, oral, rectal, subcutaneous, transdermal and
      intranasal administration.
AB  - Ketamine is a parenteral anesthetic agent that provides analgesic activity at sub
      anesthetic doses. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with
      opioid receptor activity. Controlled studies and case reports on ketamine
      demonstrate efficacy in neuropathic and nociceptive pain. Because ketamine is a
      phencyclidine analogue, it has some of the psychological adverse effects found
      with that hallucinogen, especially in adults. Therefore, ketamine is not
      routinely used as an anesthetic in adult patients. It is a frequently used
      veterinary anesthetic, and is used more frequently in children than in adults.
      The psychotomimetic effects have prompted the DEA to classify ketamine as a
      Schedule III Controlled Substance. A review of the literature documents the
      analgesic use of ketamine by anesthesiologists and pain specialists in patients
      who have been refractory to standard analgesic medication regimens. Most reports
      demonstrate no or mild psychotomimetic effects when ketamine is dosed at sub
      anesthetic doses. Patients who respond to ketamine tend to demonstrate dramatic
      pain relief that obviates the desire to stop treatment due to psychotomimetic
      effects (including hallucinations and extracorporeal experiences). Ketamine is
      approved by the FDA for intravenous and intramuscular administration. Use of this
      drug by the oral, intranasal, transdermal, rectal, and subcutaneous routes has
      been reported with analgesic efficacy in treating nociceptive and neuropathic
      pain. Ketamine also has been reported to produce opioid dose sparing and good
      patient acceptance. A transdermal formulation is currently under patent review in
      Brazil and an intranasal formulation is currently undergoing phase I/II clinical
      trials.

PMID- 14640354
TI  - Self-treatment with oral transmucosal fentanyl citrate to prevent emergency room
      visits for pain crises: patient self-reports of efficacy and utility.
AB  - Ninety (90) patients with chronic pain who were treated with a long-acting opioid
      were instructed on use of oral transmucosal fentanyl citrate (OTFC) for self
      treatment of emergency pain flares. Eighty-six (95.6%) believed OTFC was
      effective and safe for self-treatment of emergency pain flares, and 71 (78.8%)
      believed they had prevented one or more emergency room visits for treatment of
      pain flares. A subgroup of 45 patients who had collectively used OTFC for 375
      months, based on their past experience, estimated they had prevented 1.26
      emergency room visits per month per patient. OTFC should be further studied for
      cost-savings and effectiveness in self-treatment of emergency pain flares.

PMID- 14640355
TI  - Removing meperidine from the health-system formulary--frequently asked questions.
AB  - Meperidine is FDA-approved for relieving moderate to severe pain and has been
      widely used since its introduction in the 1930s. However, the drug is no longer
      considered a first-line analgesic. Many clinicians recommend that meperidine be
      removed from health-systems or that its use be restricted, due to concerns about
      adverse reactions, drug interactions, and normeperidine neurotoxicity. In
      addition, clinical evidence shows that meperidine has no advantage over other
      opioids for biliary colic or pancreatitis. The formulary status of meperidine has
      been extensively discussed at University of Utah Hospitals and Clinics. The
      Pharmacy and Therapeutics Committee has been working with hospital staff to
      assess the impact of either removing meperidine from the formulary, or limiting
      its use. The Drug Information Service developed this document to help pharmacists
      respond to prescribers' questions and to alleviate the prescribers' concerns
      about these changes. Information is provided comparing meperidine with other
      opioids, including dosage equivalency, pharmacodynamics, pharmacokinetics, cost,
      adverse effects, and drug interactions. Where available, alternatives to
      meperidine are suggested for various indications.

PMID- 14640356
TI  - Pain relief from baclofen analgesia in a neuropathic pain patient who failed
      opioid and pharmacotherapy: case report.
AB  - A case report and discussion of a 64-year-old white female who presented with
      uncontrolled pain in several body areas despite massive oral controlled release
      morphine use is presented. Her pain was not associated with much spasticity. This
      patient responded remarkably to intrathecal baclofen even after the opioid was
      tapered and discontinued. The potential usefulness of baclofen in seemingly
      opioid-resistant chronic pain is discussed.

PMID- 14640357
TI  - Defining hospice and palliative care: some further thoughts.
AB  - Widespread acceptance of hospice in the United States has contributed to
      increased public and professional interest in improved care, not only for dying
      persons, but for persons undergoing treatment for conditions that may not pose an
      immediate threat to their life. 'Palliative care' has been brought into use to
      denote care that covers a broader category of patients who do not necessarily
      have a medical condition that is not, at present, life threatening. The use of
      two related and overlapping terms by health care professionals is confusing and,
      in the absence of clear definitions, has contributed to needless controversy.
      Hospice has a specific meaning in the United States. Palliative care, once used
      as a euphemism for hospice, now has several meanings. This paper is designed to
      explore the historical evolution of both terms and to reduce the confusion and
      controversy surrounding their current application.

PMID- 14640358
TI  - Pain and palliative care in The Cochrane Library; Issue number 4, 2001.
AB  - The Cochrane Library of systematic reviews is published quarterly. Nine of the 62
      new reviews published in Issue 4 for 2001 in February 2002 are relevant to pain
      and palliative care. Annotated bibliographies for those nine reviews are
      provided.

PMID- 14640359
TI  - Analgesic issues in palliative care, furthering our understanding of pain, the
      stability and cost of opioid infusion therapy, and opioid effectiveness doses in
      nociceptive and neuropathic pain.
AB  - Literature relating to analgesic issues, pain mechanisms and management, costs of
      opioid infusions, and the opioids dosing for nociceptive and neuropathic pain are
      reviewed in the context of palliative care.

PMID- 14640360
TI  - Outcomes research: what it is and what it isn't.
AB  - This paper introduces a new series in the Journal that will address Outcomes
      Research and Pharmacoeconomics in Pain & Palliative Care. The goal of the series
      is to provide an overview of the field of outcomes research that will be geared
      to clinicians, and to review the outcomes literature in the area of Pain and
      Palliative Care. This paper defines the common types of outcomes research that
      are relevant to pain and symptom control. There are a lot of misconceptions about
      the field including some who look at outcomes research as not really science and
      not adding to our knowledge about drugs and drug use. To the contrary, outcomes
      research is a powerful tool, but like many others it has limitations and it is
      important to understand both what outcomes research is, and what it isn't.

PMID- 14640361
TI  - Questions and answers about fibromyalgia.
AB  - Information for patients about fibromyalgia syndrome and its treatment that has
      been compiled in a question and answer format by the National Institute of
      Arthritis and Musculoskeletal and Skin Diseases is presented.

PMID- 14640362
TI  - Evidence-based measures of pain management.

PMID- 14640363
TI  - Cognitive behavioral therapy and exercise for chronic fatigue syndrome.

PMID- 14640365
TI  - USP launches dietary supplement certification program.

PMID- 14640364
TI  - Hospitals and hospices improve care for chronically and terminally ill.

PMID- 14640366
TI  - Filling the shelves--is there any room for improvement?

PMID- 14640367
TI  - The current status of laser applications in dentistry.
AB  - A range of lasers is now available for use in dentistry. This paper summarizes
      key current and emerging applications for lasers in clinical practice. A major
      diagnostic application of low power lasers is the detection of caries, using
      fluorescence elicited from hydroxyapatite or from bacterial by-products. Laser
      fluorescence is an effective method for detecting and quantifying incipient
      occlusal and cervical carious lesions, and with further refinement could be used
      in the same manner for proximal lesions. Photoactivated dye techniques have been
      developed which use low power lasers to elicit a photochemical reaction.
      Photoactivated dye techniques can be used to disinfect root canals, periodontal
      pockets, cavity preparations and sites of peri-implantitis. Using similar
      principles, more powerful lasers can be used for photodynamic therapy in the
      treatment of malignancies of the oral mucosa. Laser-driven photochemical
      reactions can also be used for tooth whitening. In combination with fluoride,
      laser irradiation can improve the resistance of tooth structure to
      demineralization, and this application is of particular benefit for susceptible
      sites in high caries risk patients. Laser technology for caries removal, cavity
      preparation and soft tissue surgery is at a high state of refinement, having had
      several decades of development up to the present time. Used in conjunction with
      or as a replacement for traditional methods, it is expected that specific laser
      technologies will become an essential component of contemporary dental practice
      over the next decade.

PMID- 14640368
TI  - Diagnosis and management of unusual dental abscesses in children.
AB  - Although the majority of dental abscesses in children originate from dental
      caries or trauma, a few are associated with unusual conditions which challenge
      diagnosis and management. Recent research findings have shed light on these
      unusual entities and greatly improved understanding of their clinical
      implications. These conditions include developmental abnormalities such as dens
      invaginatus in which there is an invagination of dental tissues into the pulp
      chamber and dens evaginatus in which a tubercle containing pulp is found on the
      external surface of a tooth crown. In addition, inherited conditions which show
      abnormal dentine such as dentine dysplasia, dentinogenesis imperfecta, and
      osteogenesis imperfecta predispose the dentition to abscess formation.
      Furthermore, 'spontaneous' dental abscesses are frequently encountered in
      familial hypophosphataemia, also known as vitamin D-resistant rickets, in which
      there is hypomineralization of dentine and enlargement of the pulp. In addition
      to developmental conditions, there are also acquired conditions which may cause
      unusual dental abscesses. These include pre-eruptive intracoronal resorption
      which was previously known as 'pre-eruptive caries' or the 'fluoride bomb'. In
      addition, some undiagnosed infections associated with developing teeth are now
      thought to be the mandibular infected buccal cysts which originate from infection
      of the developing dental follicles. In the present paper, these relatively
      unknown entities which cause unusual abscesses in children are reviewed with the
      aim of updating the general practitioner in their diagnosis and management.

PMID- 14640369
TI  - Access to dental care by young South Australian adults.
AB  - BACKGROUND: Despite reported concern over the dental care of young adults little
      research has been done on their use of dental services in Australia. The aim of
      this study was to investigate the patterns of dental utilization of young South
      Australian adults aged 20-24 years. METHODS: A random sample of 2300 young adults
      was selected from the electoral roll. Partial or complete addresses and possible
      phone numbers were obtained for 1921 persons. Telephone interviews were conducted
      for 1261 subjects to obtain information on socio-demographics, health behaviour
      and dental visiting (response rate 65.6 per cent). RESULTS: One third of young
      adults (34 per cent) had not made a dental visit in the previous two years and 38
      per cent usually visited for a problem rather than a check-up. Making a dental
      visit in the last two years was significantly associated with a number of socio
      demographic variables including age and gender, with holders of private dental
      insurance and those who have not avoided care because of cost having higher odds
      of making a visit and males and government concession card holders having lower
      odds of visiting. Usual reason for visiting a dentist for a problem was
      significantly associated with no private dental insurance, holding a government
      concession card, no tertiary education and avoiding care because of cost.
      CONCLUSIONS: This study suggests that demographic and economic factors influenced
      use of dental services and reason for visiting of young South Australian adults.

PMID- 14640370
TI  - Pits and fissures: relative space contribution in fissures from sealants,
      prophylaxis pastes and organic remnants.
AB  - BACKGROUND: Previous studies by the authors have looked at the nature of the
      fissure system of human permanent molars and premolars, and has provided evidence
      for the presence of a prismless layer of enamel. It was noted during these
      studies that the fissure spaces were often occupied by material other than the
      fissure sealant. The aim of this study was to define these materials and to look
      at the percentage contribution of each to the sealed fissure space. METHODS: A
      sample of teeth, both molars and premolars, were sealed with an unfilled fissure
      sealant after prophylaxis with a coloured prophylaxis paste. In one group, the
      crown of the tooth was removed by dissolution in hydrochloric acid following
      placement of the sealant. This revealed a negative image of the fissure system
      and its contents. The second group of teeth was sectioned following sealing, and
      the contents of the fissure space were analyzed. RESULTS: The negative image of
      the fissure system displayed the fissure contents by colour and the sectioned
      teeth were able to be computer analyzed to establish the relative contribution of
      sealant, prophylaxis paste and organic material to the fissure space.
      CONCLUSIONS: Sealant contribution was in the range of 14-96 per cent, prophylaxis
      paste from 0-50 per cent and organic remnants 0-55 per cent. The presence of
      these last two components could contribute to sealant loss.

PMID- 14640371
TI  - Clinical evaluation of an 'all-in-one' bonding system to non-carious cervical
      lesions--results at one year.
AB  - BACKGROUND: The recent trend in using dentine adhesives is to simplify the number
      of steps required for bonding. The simplest are now the so-called 'all-in-one'
      products which combine the etching, priming and bonding steps into a single
      application. However, few clinical trials have been reported using this type of
      material. The current study reports the one-year results of a clinical trial with
      One-Up Bond F and Palfique Estilite resin composite. METHODS: Fifty-one non
      undercut non-carious cervical lesions were restored with One-Up Bond F and
      Palfique Estilite in 15 patients (mean age 57.5 years). Restorations were
      evaluated at six months and one year for presence or absence and for marginal
      staining using standardized colour photographs for comparison. RESULTS: At one
      year, 42 restorations could be evaluated and all were intact. Slight marginal
      staining was observed around three restorations but was considered to be of no
      clinical significance. CONCLUSIONS: One-Up Bond F with Palfique Estelite shows
      good promise for the restoration of non-carious cervical lesions.

PMID- 14640372
TI  - Training for dentists in smoking cessation intervention.
AB  - BACKGROUND: Although dentists are ideally placed to deliver smoking cessation
      advice and assistance to their patients, smoking cessation interventions are not
      often incorporated as a routine part of dental care. Research is needed to
      identify factors that facilitate and inhibit dentists' capacities to deliver
      smoking cessation advice. METHODS: An initial focus group discussion was
      conducted in Melbourne with 10 dentists. Six Victorian country dentists were
      interviewed in depth by telephone. Following this qualitative data collection, a
      random sample of 250 dentists (response rate of 57 per cent) was interviewed by
      telephone. Dentists were asked about their perceived role, current practices,
      knowledge of resources and services and opinions on training in relation to
      smoking cessation. RESULTS: Dentists are willing to ask and advise patients about
      smoking, but are less inclined to assist patients to quit or arrange follow-up.
      Dentists are more likely to implement one-off, opportunistic interventions rather
      than take a systematic preventive approach. Dentists are interested in attending
      further education and say they require training to be relevant to the context of
      their day-to-day running of the dental practice. CONCLUSIONS: Training should aim
      to legitimize the dentist's role in smoking cessation and provide strategies and
      resources so that dentists can practise interventions as part of their day-to-day
      work.

PMID- 14640373
TI  - The split denture: a new technique for artificial saliva reservoirs in mandibular
      dentures.
AB  - Xerostomia is a relatively common complaint that can make the wearing of dentures
      very uncomfortable for affected individuals. To help overcome this problem, a
      number of techniques have been proposed for incorporating reservoirs, containing
      salivary substitutes, into dentures. These have had varying degrees of success.
      This paper presents a case of a patient suffering from xerostomia who was
      successfully treated with a new form of reservoir denture. This new split-denture
      technique resulted in a reservoir denture that provided good lubrication of the
      oral tissues, was easily cleaned by the wearer and was produced from routine
      denture materials. Details of its design, construction and other potential
      applications are also presented.

PMID- 14640374
TI  - Acute leukaemia presenting as oral ulceration to a dental emergency service.
AB  - Leukaemia is a neoplastic disease characterized by an excessive proliferation of
      immature white blood cells and their precursors. Oral lesions may be the
      presenting feature of acute leukaemias, which can be rapidly fatal if left
      untreated. This report describes the case of a 22-year-old female who presented
      to a dental emergency department with oral manifestations of acute leukaemia. It
      outlines the role of oral lesions in the diagnosis of acute leukaemias and
      emphasizes the importance of immediate referral by general dental practitioners.

PMID- 14640375
TI  - Sperm pathology: a step beyond descriptive morphology. Origin, characterization
      and fertility potential of abnormal sperm phenotypes in infertile men.
AB  - Sperm pathology is presented as the discipline of characterizing structural and
      functional deficiencies in abnormal spermatozoa. This concept complements that of
      sperm morphology mainly concerned with the appearance of spermatozoa. These two
      notions collaborate in providing correlations of prognostic value with sperm
      fertilizing capacity, explaining the mechanisms of sperm inefficiency, suggesting
      strategies to improve fertilization and opening a door to molecular genetic
      studies. Phenotypes of genetic origin involving sperm heads, flagella and the
      neck region are presented describing their clinical manifestations, sperm
      structure, cytochemistry and genetic background. When available, animal models
      are used to highlight possible genetic mechanisms. Sperm pathologies secondary to
      andrological conditions or environmental factors are described, stressing the non
      specific nature of the sperm response to noxious agents. The available literature
      on the prognostic value of sperm pathologies in ICSI is also reviewed. Flagellar
      anomalies bear a good prognosis, but those affecting the acrosome, sperm
      chromatin and the neck region entail an increasing chance of failure, which
      highlights the differential roles played by specific sperm components in
      fertilization, implantation and early embryonic development. A final discussion
      is devoted to genetic counselling and the risks involved in using immotile or
      abnormal spermatozoa in assisted reproduction.

PMID- 14640376
TI  - Patient predictors for outcome of gonadotrophin ovulation induction in women with
      normogonadotrophic anovulatory infertility: a meta-analysis.
AB  - A systematic review was conducted to determine whether initial screening
      characteristics of women with normogonadotrophic anovulatory infertility predict
      clinically significant outcomes of ovulation induction with gonadotrophins, and
      to obtain pooled estimates of their predictive value through meta-analysis. Only
      those studies in which pre-treatment screening characteristics (such as body mass
      index, serum LH and androgens, insulin sensitivity and ultrasound appearance of
      ovaries) were related to outcome parameters (such as total amount of FSH
      administered, cancellation, ovulation, pregnancy and miscarriage), were included
      in this analysis. Thirteen studies fulfilled the inclusion criteria. A positive
      association was seen in all studies between the level of obesity (definition
      applied as assessed by individual studies) and total amount of FSH administered
      [weighted mean difference (WMD) of 771 IU (95% confidence interval (CI): 700
      842)]. Pooled odds ratios (OR) of 1.86 (95% CI: 1.13-3.06) and 0.44 (95% CI: 0.31
      0.61) were found between obesity with cancellation and ovulation respectively.
      Pooled analysis did not show a significant association between obesity and
      pregnancy rate. The pooled OR for obese versus non-obese women and miscarriage
      rate was significant [3.05 (95% CI: 1.45-6.44)]. Association measures between
      insulin resistance (definition applied as assessed by individual studies) and
      total amount of FSH administered produced a WMD of 351 (95% CI: 73-630) IU. A
      pooled OR of 0.29 (95% CI: 0.10-0.80) was found for insulin resistance with
      pregnancy rate. The pooled OR for insulin resistance (hyperinsuliaemia versus
      normoinsuliaemia) and miscarriage rate was not significant. A pooled OR of 1.04
      (95% CI: 1.01-1.07) was found for LH (IU/l) with pregnancy rate. The pooled OR
      for LH and miscarriage rate was not significant. Finally, pooled analysis did not
      find a significant association between testosterone and pregnancy rate. In
      conclusion, the best available evidence, though limited, suggests that the most
      clinically useful predictors of gonadotrophin ovulation induction outcome in
      normogonadotrophic women are obesity and insulin resistance.

PMID- 14640377
TI  - Rethinking gamete/embryo isolation and culture with microfluidics.
AB  - IVF remains one of the most exciting modern scientific developments and continues
      to have a tremendous impact on people's lives. Since its beginnings, scientists
      have studied and critically analysed the techniques in order to find ways to
      improve outcomes; however, little has changed with the actual technology and
      equipment of IVF. Semen is still processed in test tubes and fertilization and
      culture still occurs in culture dishes. New technological possibilities exist
      with the burgeoning advancement of microfluidic technology. Microfluidics is
      based on the behaviour of liquids in a microenvironment. Although a young field,
      many developments have occurred which demonstrate the potential of this
      technology for IVF. In this review, we briefly discuss the physical principles of
      microfluidics and highlight some previous utilizations of this technology,
      ranging from chemical analysis to cell sorting. We then present the designs and
      outcomes for microfluidic devices utilized thus far for each step in IVF: gamete
      isolation and processing, fertilization, and embryo culture. Finally, we discuss
      and speculate on the ultimate goal of this technology--development of a single,
      integrated unit for in-vitro assisted reproduction techniques.

PMID- 14640378
TI  - Oocyte freezing: here to stay?
AB  - Oocyte freezing is an established technology but, in contrast to embryo freezing,
      it has very limited application in clinical IVF programmes. Is there a chance
      that oocyte freezing will become an integrated routine in assisted reproductive
      technology? The delicate cytological architecture of the oocyte with a cold
      sensitive spindle and a hardening zona have made the frozen oocyte 'unwanted' in
      assisted reproductive technology. Nevertheless, empirical improvements in
      freezing protocols and the use of ICSI for fertilization have led to an
      increasing number of live births. This mitigates against a simple ban on oocyte
      freezing. While efficiency of oocyte freezing can certainly be further improved
      by basic research, it is clear that there are humanitarian reasons for
      considering oocyte freezing as a future fully utilized assisted reproductive
      technology. The storage of the female genome as a particulate entity can provide
      an alternative in case of moral, ethical, legal or religious concerns about
      embryo freezing. Oocyte freezing can also offer hope for oocyte donation and
      preservation of fertility for women facing ovarian loss. The message is one of
      cautious optimism when looking for a place for oocyte freezing in routine
      assisted reproductive technology.

PMID- 14640379
TI  - Applications of ovarian tissue transplantation in experimental biology and
      medicine.
AB  - Nowadays, high-dose chemotherapy and radiotherapy treatments for cancer are more
      effective but can severely affect the ovarian follicular store, compromising the
      fertility of surviving young patients. A promising alternative to prevent
      fertility loss in these patients is the cryopreservation and transplantation of
      ovarian tissue. Slices of animal and human ovarian tissue have been shown to
      survive the cryopreservation process. After transplantation, follicular
      development and restoration of hormone secretion have been observed in animal and
      human studies. This review addresses recent developments on ovarian tissue
      transplantation in animals and humans. We also illustrate the indications and
      technical difficulties of the procedure and the ethical issues that should be
      considered.

PMID- 14640380
TI  - Gestational surrogacy.
AB  - Gestational surrogacy is a treatment option available to women with certain
      clearly defined medical problems, usually an absent uterus, to help them have
      their own genetic children. IVF allows the creation of embryos from the gametes
      of the commissioning couple and subsequent transfer of these embryos to the
      uterus of a surrogate host. The indications for treatment include absent uterus,
      recurrent miscarriage, repeated failure of IVF and certain medical conditions.
      Treatment by gestational surrogacy is straightforward and follows routine IVF
      procedures for the commissioning mother, with the transfer of fresh or frozen
      thawed embryos to the surrogate host. The results of treatment are good, as would
      be expected from the transfer of embryos derived from young women and transferred
      to fit, fertile women who are also young. Clinical pregnancy rates achieved in
      large series are up to 40% per transfer and series have reported 60% of hosts
      achieving live births. The majority of ethical or legal problems that have arisen
      out of surrogacy have been from natural or partial surrogacy arrangements. The
      experience of gestational surrogacy has been largely complication-free and early
      results of the follow-up of children, commissioning couples and surrogates are
      reassuring. In conclusion, gestational surrogacy arrangements are carried out in
      a few European countries and in the USA. The results of treatment are
      satisfactory and the incidence of major ethical or legal complications has been
      limited. IVF surrogacy is therefore a successful treatment for a small group of
      women who would otherwise not be able to have their own genetic children.

PMID- 14640381
TI  - Menstrual disorders in adolescence: investigation and management.
AB  - Menstrual disorders in adolescence may present diagnostic and management
      challenges for the gynaecologist. This review will describe the common and
      uncommon menstrual disorders that may arise in early reproductive life, together
      with guidance on their investigation and management.

PMID- 14640382
TI  - Natural history models for hepatitis C-related liver disease: different disease
      progression parameters for different settings.
AB  - An understanding of the natural history of hepatitis C virus (HCV) infection has
      improved in recent years. Estimates of liver disease progression among people
      with chronic hepatitis C have been developed from various study populations,
      including liver clinics, post-transfusion hepatitis C cohorts and community-based
      cohorts. These estimates can be used in hepatitis C natural history models;
      however, they need to be matched to differing requirements. Estimation and
      projection of liver disease burden at the population level requires estimates of
      HCV prevalence and incidence, and disease progression among all people with
      chronic hepatitis C. Liver disease progression based on community cohorts would
      appear the most appropriate for a population level model. In contrast, models
      that examine the cost-effectiveness of antiviral therapy for people with chronic
      hepatitis C require disease progression estimates from the treatment setting.
      Further models are required to determine individual prognosis and should be based
      on an assessment of cofactors for liver disease progression.

PMID- 14640383
TI  - Protection from HIV-1 infection of primary CD4 T cells by CCR5 silencing is
      effective for the full spectrum of CCR5 expression.
AB  - Stable gene silencing by RNA interference (RNAi) can be achieved by expression of
      small hairpin RNAs (shRNAs) from RNA polymerase III promoters. We have tested
      lentiviral vectors expressing shRNAs targetting CCR5 in primary CD4 T cells from
      donors representing various CCR5 and CCR2 genetic backgrounds covering the full
      spectrum of CCR5 expression levels and permissiveness for HIV-1 infection. A
      linear decrease in CCR5 expression resulted in a logarithmic decrease in cellular
      infection, giving up to three logs protection from HIV-1 infection in vitro.
      Protection was maintained at very high multiplicity of infection. This and other
      recent reports on RNAi should open a debate about the use of RNAi gene therapy
      for HIV infection.

PMID- 14640384
TI  - Total lymphocyte count as a possible surrogate of CD4 cell count to prioritize
      eligibility for antiretroviral therapy among HIV-infected individuals in resource
      limited settings.
AB  - OBJECTIVE: To characterize the value of total lymphocyte counts in predicting
      risk of death among patients initiating triple combination antiretroviral
      therapy. METHODS: Study subjects included antiretroviral-naive persons aged 18
      years or older who initiated treatment with triple combination therapy between
      August 1 1996 and September 30 1999 in a population-based observational cohort of
      HIV-infected individuals. Total lymphocyte counts as well as CD4 count and plasma
      viral load were assessed at baseline. Separate Cox proportional hazards models
      were devised to evaluate the effect on survival of total lymphocyte count in lieu
      of or with CD4 count after adjustment for other prognostic factors including
      plasma viral load. RESULTS: A total of 733 antiretroviral-naive persons initiated
      triple drug combination antiretroviral therapy over the study period with a
      median follow-up of 29.5 months. In the first analysis, only baseline CD4 cell
      counts of 50-199 cells/microl or less than 50 microl were associated with an
      increased risk of mortality [adjusted relative risk (ARR) 2.90; 95% CI: 1.40,
      5.98] and (ARR 6.30; 95% CI: 2.93, 13.54), respectively. When CD4 counts were
      excluded from the analysis as if unavailable, total lymphocyte count of between
      0.8 and 1.4 G/I, and less than 0.8 G/I were both significantly associated with an
      increased risk of mortality (ARR 2.36; 95% CI: 1.16, 4.78) and (ARR 6.17; 95% CI:
      2.93, 13.01), respectively. CONCLUSION: Total lymphocyte count may provide a
      simple and cost-effective alternative for prioritizing therapy initiation in
      resource-limited settings. Our results suggest that, if appropriately validated,
      judicious application of total lymphocyte counts could overcome one of the
      practical obstacles to more widespread provision of antiretroviral therapy in
      resource-poor settings.

PMID- 14640385
TI  - Medium-term survival, morbidity and immunovirological evolution in HIV-infected
      adults receiving antiretroviral therapy, Abidjan, Cote d'Ivoire.
AB  - OBJECTIVES: To evaluate survival, morbidity, and CD4 and viral load (VL)
      evolution in HIV-infected adults receiving antiretroviral therapy (ART) in Cote
      d'Ivoire. METHODS: Since 1996, 723 HIV-infected adults have been followed up in
      the ANRS 1203 cohort study in Abidjan. For those patients who received ART, we
      describe data between ART initiation and August 2002. RESULTS: One-hundred-and
      one adults (61% women) were followed up under ART for a median of 17 months. At
      ART initiation, median age, CD4 count and VL were 36 years, 135/mm3 and 5.3 log10
      copies/ml, respectively. Initial ART regimens were two nucleoside reverse
      transcriptase inhibitors (NRTIs) plus one protease inhibitor in 74 patients, two
      NRTIs plus one non-nucleoside reverse transcriptase inhibitor in 16, and two
      NRTIs in 11. No patient was lost to follow-up. The most frequent causes of severe
      morbidity were bacterial infections [11.6/100 person-years (PY), 95% CI: 7.2
      18.7], drug-related events (6.5/100 PY, 3.5-12.0), tuberculosis (3.1/100 PY, 1.3
      7.4) and malaria (3.1/100 PY, 1.3-7.4). The incidence of death was 3.0/100 PY
      (1.1-8.0) in patients with baseline CD4 > or = 50/mm3 and 16.1/100 PY (7.2-35.9)
      in patients with CD4 < 50/mm3. Fifty percent of causes of death were active
      infections pre-existing ART initiation, mainly atypical mycobacteriosis. After 1
      year, 51% of patients had undetectable VL, 28% had detectable VL reduced by more
      than 0.5 log10 copies/ml since ART initiation, and the median gain in CD4 was
      +115/mm3. CONCLUSION: Medium-term survival under ART may be as good in Africa as
      in industrialized countries, provided that patients benefit from access to care
      for opportunistic infections, including bacterial diseases, tuberculosis and
      malaria.

PMID- 14640386
TI  - Modest decreases in NNRTI susceptibility do not influence virological outcome in
      patients receiving initial NNRTI-containing triple therapy.
AB  - OBJECTIVE: To assess the prevalence of modest (< 10-fold) decreases in baseline
      non-nucleoside reverse transcriptase inhibitor (NNRTI) susceptibility and their
      impact on virological response to NNRTI-containing triple therapy in drug-naive
      individuals. METHODS: Baseline HIV resistance phenotype, genotype and response to
      therapy were examined retrospectively for all antiretroviral-naive individuals
      initiating therapy with two nucleoside analogues and an NNRTI in British
      Columbia, Canada, between 05/1997 and 08/1999 (n = 279), followed until July 31
      2001. Time to viral suppression (first of at least two consecutive plasma viral
      loads < 400 copies HIV RNA copies/ml) and viral rebound (to > or = 400 copies/ml
      after first pVL < 400 copies HIV RNA copies/ml), were estimated by Kaplan-Meier
      methods. Multivariate analyses were performed using Cox proportional hazards
      regression. RESULTS: Nevirapine was the most commonly prescribed NNRTI (96%).
      Four- to 10-fold decreased susceptibility to NNRTIs was observed in > 30% of
      untreated individuals at baseline, an observation strongly driven by decreased
      susceptibility to delavirdine (22.4%). A > 10-fold decrease in susceptibility to
      any NNRTI was observed only rarely (< 2%). There was no association between four-
      and 10-fold decreased baseline susceptibility to NNRTIs and virological outcome
      (P > 0.05). In multivariate analyses, the strongest predictors of poor
      virological response to NNRTI-based therapy were baseline plasma viral load and
      the proportion of time on therapy in the first year of follow-up. There was no
      relationship between the presence of previously reported mutations associated
      with decreased NNRTI susceptibility (at codons 135 and 283 in HIV reverse
      transcriptase) and virological response. CONCLUSIONS: These data suggest that the
      clinically significant level of resistance to NNRTIs, particularly nevirapine, in
      drug-naive individuals is likely greater than four- to 10-fold.

PMID- 14640388
TI  - Drug resistance mutations during structured treatment interruptions.
AB  - BACKGROUND: We assessed whether treatment interruptions induce selection of
      mutations associated with drug resistance in the Swiss-Spanish Intermittent
      Treatment Trial (SSITT). Patients had been on HAART without previous failure and
      had undetectable viraemia for at least 6 months. Their HAART was interrupted for
      2 weeks and restarted for 8 weeks. After four of these cycles, treatment was
      definitively interrupted at week 40. METHODS: Genotypic resistance testing was
      performed in 87/97 Swiss patients: in those failing treatment before week 40, at
      the time of first viral rebound > 500 copies/ml off treatment and preceding
      failure to reach RNA < 50 copies/ml after 8 weeks of re-treatment; for patients
      without virological failure, on the first sample with HIV-1 RNA > 1000 copies/ml
      after week 40. RESULTS: Mutations associated with drug resistance were detected
      in 9/25 (36%) patients with virological failure during the first 40 weeks and in
      6/59 (10%) patients after week 40. Overall, drug resistance mutations were
      detected in 17% of patients, all but two with the 184V/I mutation. Among the 74
      patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%)
      patients. A wild-type codon at position 184 was detected in previous samples in
      all but two. The relative risk for virological failure was 2.55-fold higher in
      patients with the M184V/I mutation than in patients without detectable mutation
      (P=0.007). CONCLUSIONS: The M184V/I mutation is frequently selected during
      repeated treatment interruptions.

PMID- 14640387
TI  - Effects of metformin or gemfibrozil on the lipodystrophy of HIV-infected patients
      receiving protease inhibitors.
AB  - BACKGROUND: Hypertriglyceridaemia and insulin resistance are common in HIV
      infected patients treated with protease inhibitors, particularly in those with
      lipodystrophy. Whether a therapeutic approach addressed to those metabolic
      abnormalities may have any impact on body fat is not clear. METHODS: Patients on
      stable antiretroviral therapy containing protease inhibitors, with abdominal
      obesity defined by increased waist-to-hip ratio, and plasma triglycerides >200
      mg/dl, were randomized to receive blind medication consisting of metformin 850
      mg, gemfibrozil 600 mg or placebo every 12 h for 1 year. Weight, height, waist
      and hip were measured, and fasting blood analyses, including at least CD4 cell
      count, plasma HIV-1 RNA, lactate, glucose, insulin, triglycerides, total, HDL and
      LDL cholesterol were performed at baseline and every 3 months. An oral glucose
      tolerance test, and assessments of total and regional fat by bioimpedance
      analysis and sonography, respectively, were also done at baseline, 6 and 12
      months. RESULTS: One-hundred-and-eight patients were randomized to placebo
      (n=36), gemfibrozil (n=37) or metformin (n=35). There was absolute loss of total
      and regional fat in the three arms without significant changes in the waist-to
      hip ratio. However, the loss of fat in patients on gemfibrozil was significantly
      lower than in patients on placebo. No patient discontinued study drugs due to
      adverse effects. CONCLUSION: In this population of HIV-infected patients, there
      was a loss of fat along time. The finding of relative preservation of fat
      associated with gemfibrozil therapy deserves further investigation in the search
      of potential effective therapies for lipodystrophy in HIV-infected subjects.

PMID- 14640389
TI  - Intracellular disposition and metabolic effects of zidovudine, stavudine and four
      protease inhibitors in cultured adipocytes.
AB  - OBJECTIVE: The pathogenesis of lipodystrophy caused by the HIV protease
      inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) is
      unclear. We have investigated the disposition of these drugs in adipocytes and
      the consequent effect on adipocyte metabolism and viability. DESIGN: Laboratory
      study utilizing two murine cell lines, 3T3-L1 and 3T3-F442A. METHODS:
      Intracellular NRTI phosphate and PI concentrations were determined by HPLC and
      HPLC-MS/MS, respectively. The cytotoxicity of the drugs was examined on the
      different adipogenic stages together with their effects on glucose uptake plus or
      minus insulin, and on glycerol and triglyceride levels. RESULTS: There was rapid
      intracellular accumulation and phosphorylation of [3H]-zidovudine and -stavudine
      to their phosphate metabolites in adipocytes. The NRTIs were not cytotoxic, did
      not affect preadipocyte protein synthesis and did not inhibit adipogenesis or
      induce lipolysis. PIs accumulated in adipocytes
      (nelfinavir>saquinavir>ritonavir>indinavir). All PIs, except indinavir, were
      cytotoxic and inhibited adipogenesis, increased lipolysis and impaired
      preadipocyte protein synthesis. PIs inhibited glucose uptake in the rank order:
      indinavir>saquinavir>ritonavir>nelfinavir. CONCLUSION: These data demonstrate
      that PIs may play a role in the insulin resistance observed in lipodystrophy by
      affecting glucose uptake, adipogenesis and lipolysis. NRTIs alone do not seem to
      have any effect on adipocyte metabolism despite undergoing phosphorylation to
      their triphosphorylated anabolites, although their effects in combination with
      PIs in perturbing adipocyte metabolism warrants further investigation.

PMID- 14640390
TI  - Predictors of the virological response to a change in the antiretroviral
      treatment regimen in HIV-1-infected patients enrolled in a randomized trial
      comparing genotyping, phenotyping and standard of care (Narval trial, ANRS 088).
AB  - OBJECTIVE: To identify predictors of the virological response to antiretroviral
      therapy in patients in whom initial therapy has failed. METHODS: The Narval trial
      was designed to compare phenotyping, genotyping and standard of care for the
      choice of antiretroviral therapy in patients in whom a protease inhibitor (PI)
      containing regimen had failed. Virological success was defined as viral load
      below 200 copies/ml at week 12. Baseline variables including demographic,
      clinical and biological characteristics, HIV reverse transcriptase and protease
      mutations, the randomization arm, the drugs prescribed, as well as adherence to
      treatment and plasma concentrations of PIs and non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) at week 12 were tested in the model. Variables
      that were significantly associated with virological success in univariate
      analysis were included in a logistic regression model. RESULTS: Five-hundred-and
      forty-one patients were randomized. Virological success at week 12 was obtained
      in 200 patients. In multivariate analysis, the following factors were
      significantly associated with virological success: prescription of efavirenz to
      NNRTI-naive patients (OR=4.37; 95% CI: 2.76-6.90), randomization to the
      genotyping arm (OR=2.13, 1.20-3.79), prescription of lamivudine (OR=1.69, 1.01
      2.83) and prescription of abacavir to abacavir-naive patients (OR=1.66, 1.02
      2.72). Factors significantly associated with virological failure were
      prescription of nelfinavir (OR=0.30, 0.13-0.68), a high baseline viral load
      (OR=0.37, 0.28-0.50), the presence of at least five PI mutations (OR=0.42, 0.26
      0.66), the presence of at least three thymidine analogue mutations (OR=0.61, 0.39
      0.97) and at least 30 months of prior PI exposure (OR=0.64, 0.41-0.99).
      CONCLUSIONS: These results confirm that among heavily pretreated patients,
      prescription of efavirenz to NNRTI-naive patients is associated with a good
      virological response, while a high baseline viral load, a large number of PI
      mutations and nelfinavir prescription at baseline are associated with a poor
      virological response. Genotyping was found to be beneficial, while this was not
      the case for phenotyping. This work was presented at the XI International HIV
      Drug Resistance Workshop, Sevilla, Spain, July 3-6 2002 (Abstract N(o)133); and
      at the XIV International Conference on AIDS, Barcelona, Spain, July 7-11 2002
      (Abstract N(o)ThOrB138).

PMID- 14640391
TI  - HIV lipodystrophy case definition using artificial neural network modelling.
AB  - OBJECTIVE: A case definition of HIV lipodystrophy has recently been developed
      from a combination of clinical, metabolic and imaging/body composition variables
      using logistic regression methods. We aimed to evaluate whether artificial neural
      networks could improve the diagnostic accuracy. METHODS: The database of the case
      control Lipodystrophy Case Definition Study was split into 504 subjects (265 with
      and 239 without lipodystrophy) used for training and 284 independent subjects
      (152 with and 132 without lipodystrophy) used for validation. Back-propagation
      neural networks with one or two middle layers were trained and validated. Results
      were compared against logistic regression models using the same information.
      RESULTS: Neural networks using clinical variables only (41 items) achieved
      consistently superior performance than logistic regression in terms of
      specificity, overall accuracy and area under the ROC curve. Their average
      sensitivity and specificity were 72.4 and 71.2%, as compared with 73.0 and 62.9%
      for logistic regression, respectively (area under the ROC curve, 0.784 vs 0.748).
      The discriminating performance of the neural networks was largely unaffected when
      built excluding 13 parameters that patients may not have readily available. The
      average sensitivity and specificity of the neural networks remained the same when
      metabolic variables were also considered (total 60 items) without a clear
      advantage against logistic regression (overall accuracy 71.8%). The performance
      of networks considering also body composition variables was similar to that of
      logistic regression (overall accuracy 78.5% for both). CONCLUSIONS: Neural
      networks may offer a means to improve the discriminating performance for HIV
      lipodystrophy, when only clinical data are available and a rapid approximate
      diagnostic decision is needed. In this context, information on metabolic
      parameters is apparently not helpful in improving the diagnosis of HIV
      lipodystrophy, unless imaging and body composition studies are also obtained.

PMID- 14640392
TI  - Impact of genotypic resistance testing on selection of salvage regimen in
      clinical practice.
AB  - OBJECTIVE: To determine whether genotypic resistance testing leads to selection
      of more potent drug regimens when compared to regimens based on treatment history
      only. DESIGN: Prospective, tertiary care centre-based study. PATIENTS: One
      hundred-and-forty-five HIV-infected adults on stable antiretroviral therapy (ART)
      for >6 months experiencing virological failure. METHODS: The physicians' decision
      making process when choosing a salvage regimen was prospectively documented: at
      time of virological failure, on 'failing ART', genotyping was performed and a
      hypothetical 'clinical expert ART' based upon patient's drug history was
      documented. Subsequently, data on resistance mutations, rating by a decision
      support software and drug history were used to define 'genotyping ART'. After
      discussion with the patient, final treatment, 'new personalized ART' was chosen
      and prescribed. To compare the relative potency of the four ART regimens in a
      standardized manner, a resistance score ranging from 1 (best) to 8 (worst) based
      on drug ranking by decision support software was attributed to each ART regimen.
      Virological and immunological outcomes were analysed based on the magnitude of
      the resistance score. RESULTS: Median follow-up was 1.5 years. In all 145
      patients, median resistance scores for the stepwise selected ART regimens were:
      'failing ART': 4.5, 'clinical expert ART': 1.8, 'genotyping ART': 1.5 and 'new
      personalized ART': 2. The latter was 1.5 in patients who effectively switched to
      'new personalized ART' (n=89). Lower resistance scores translated into
      significantly improved virological response after initiation of 'new personalized
      ART'. In multivariable analysis, lower resistance scores, lower baseline HIV RNA
      levels and use of novel antiretroviral drugs were associated with the probability
      of reducing plasma viraemia to <50 copies/ml. CONCLUSIONS: This study suggests
      that treatment choices including genotype and decision support software were
      virologically superior to those based on drug history only.

PMID- 14640393
TI  - A once-daily HAART regimen containing indinavir + ritonavir plus one or two
      nucleoside reverse transcriptase inhibitors (PIPO study).
AB  - INTRODUCTION: There is an increased interest in developing once-daily regimens
      for the treatment of HIV-infected patients. A Phase II study was conducted to
      investigate the pharmacokinetics, and short-term safety and efficacy of an
      indinavir/ritonavir combination as part of a once-daily regimen. METHODS: HIV
      infected patients with either proven poor compliance to HAART regimens in the
      past or an anticipated poor compliance to such a regimen in the future were
      eligible for this study. They received a once-daily regimen consisting of
      indinavir 1200 mg, ritonavir 400 mg, and one or two nucleoside reverse
      transcriptase inhibitors (NRTIs), also administered once daily with food. A 24 h
      pharmacokinetic profile was constructed in a subset of patients. Short-term
      safety and efficacy were evaluated at 4, 12 and 24 weeks after initiation of
      treatment. RESULTS: A total of 64 patients were included in this study, of whom
      27 (42.2%) were treatment-naive. The geometric mean (+95% CI) of indinavir AUC0
      24h, Cmax and Cmin as determined in an unselected group of 16 patients were 84.9
      (69.7-103.5) mg/l x h, 12.0 (10.2-14.1) mg/l and 0.15 (0.09-0.26) mg/l,
      respectively. A large interpatient variability was observed, with five out of the
      16 subjects having a Cmin value below the minimum effective concentration of 0.10
      mg/l. During the 24 weeks of follow-up nine patients (14.1%) discontinued study
      medication, two due to medication-related toxicity. Gastrointestinal adverse
      events were reported most frequently (50.0%), followed by skin effects (45.3%),
      joint pain (9.4%) and urological complaints (7.8%). No patient developed
      nephrolithiasis. The median (+interquartile range) serum creatinine level in the
      64 patients increased slightly from 74 (63-88) micromol/l to 79 (66-92)
      micromol/l during the 24 weeks of follow-up. One new patient reached a grade 1
      elevation in serum creatinine, which normalized during the follow-up; five other
      patients with elevated serum creatinine at baseline remained stable. During the
      24 weeks of follow-up, the proportion of patients with a viral load <500
      copies/ml increased from 35.1% at baseline to 71.4% (ITT NC=F analysis) or 83.3%
      (OT analysis), and from 0% at baseline to 76.2% (ITT NC=F analysis) or 100.0% (OT
      analysis) in treatment-experienced and -naive patients, respectively. This was
      accompanied by a mean increase in CD4 cell count of 52 and 220 cells/mm3 in these
      two sub-groups, respectively. CONCLUSION: The 24-week follow-up data of this
      study indicate favourable pharmacokinetics of an indinavir/ritonavir 1200/400 mg
      combination as part of a once-daily regimen consisting also of one or two NRTIs.
      Short-term safety and efficacy were also satisfactory. Long-term follow up is
      planned to evaluate the durability of these results.

PMID- 14640394
TI  - Uridine abrogates mitochondrial toxicity related to nucleoside analogue reverse
      transcriptase inhibitors in HepG2 cells.
AB  - OBJECTIVE: To assess in vitro if uridine may be suitable to prevent or treat
      mitochondrial toxicity related to nucleoside analogue reverse transcriptase
      inhibitors (NRTIs). METHODS: Human HepG2-hepatocytes were exposed to NRTIs with
      or without uridine for 25 days. Cell growth, lactate production, intracellular
      lipids, mitochondrial DNA (mtDNA) and the ratio between the respiratory chain
      components COX II (mtDNA-encoded) and COX IV (nuclear-encoded) were measured.
      RESULTS: HepG2 cells exposed to zalcitabine (177 nM) without uridine developed a
      severe depletion of mtDNA (to 8% of wild-type mtDNA levels), resulting in a
      decline of cell proliferation and COX II levels, with increased lactate and lipid
      accumulation. Uridine fully abrogated the adverse effects of zalcitabine on
      hepatocyte proliferation and normalized lactate synthesis, intracellular lipids
      and COX II levels by adjusting mtDNA levels to about 65% of NRTI-unexposed
      control cells. This effect was dose-dependent, with a maximum at 200 microM of
      uridine. Uridine also rapidly and fully restored cell function when added to
      cells with established mitochondrial dysfunction (zalcitabine for 15 days)
      despite continued zalcitabine exposure. Uridine also normalized cell
      proliferation in HepG2 cells exposed to 36 microM of stavudine and protected
      HepG2-cells exposed to 7 microM of zidovudine + 8 microM of lamivudine
      (pyrimidine analogues), but failed to improve cell function or mtDNA in cells
      exposed to 11.8 or 118 microM of didanosine (a purine analogue). CONCLUSIONS: The
      pyrimidine precursor uridine may attenuate the mitochondrial toxicity of
      antiretroviral pyrimidine NRTIs in vitro, and its supplementation may represent a
      promising strategy in the prevention or treatment of mitochondrial toxicities in
      HIV-infected patients.

PMID- 14640395
TI  - Highly active antiretroviral therapy: physician experience and enhanced adherence
      to prescription refill.
AB  - OBJECTIVE: To identify patient and physician characteristics that may act as
      determinants of adherence to prescription refill of triple combination
      antiretroviral therapy. METHODS: A population-based analysis of antiretroviral
      therapy-naive HIV-positive men and women in British Columbia, Canada, who
      initiated triple combination therapy between August 1 1996 and October 31 1998.
      Study participants were considered adherent if they were actually dispensed
      antiretrovirals > or = 95% over the first year of therapy. Log-binomial
      regression was used to identify patient and physician characteristics associated
      with adherence to prescription refill. RESULTS: Of the 886 individuals eligible
      for analysis, 495 (56%) were > or = 95% adherent to prescription refill. In
      multivariate analysis, adherence was positively associated with increased age
      [adjusted relative rate (ARR) 1.19; 95% CI: 1.07-1.32], having a diagnosis of
      AIDS (ARR 1.66; 95% CI: 1.29-2.15), being male (ARR 1.79; 95% CI: 1.27-2.53), and
      with greater experience of the treating physician (ARR 1.27; 95% CI: 1.13-1.42).
      History of injection drug use was negatively associated with adherence to
      prescription refill (ARR 0.65; 95% CI: 0.51-0.83), as was increased pill burden
      (per pill daily) (ARR 0.95; 95% CI: 0.92-0.99). A sub-analysis of 316 patients
      who provided additional data regarding psychosocial characteristics indicated
      that adherence was positively associated with physician experience (ARR: 1.28;
      95% CI: 1.09-1.51) and being employed (ARR: 1.55; 95% CI: 1.14-2.21), and
      negatively associated with a history of injection drug use (ARR: 0.61; 95% CI:
      0.43-0.85). CONCLUSION: While patient disease stage and personal characteristics
      may play an important role in patient adherence to prescription refill of complex
      therapeutic regimens, our findings indicate that HIV-experienced physicians may
      have greater success in maintaining patients on prescribed therapy.

PMID- 14640396
TI  - Drug-resistant HIV-1 in the semen of men receiving antiretroviral therapy with
      acute sexually transmitted infections.
AB  - Sexually transmitted infections may enhance the sexual transmission of HIV-1. It
      is possible that loss of virological control in patients with such infections
      receiving antiretroviral therapy (ART) may even facilitate the transmission of
      drug-resistant HIV. We have recently demonstrated that in those on maximally
      suppressive ART this effect is reduced. We have examined the virus obtained from
      the blood plasma and seminal plasma of six HIV-1-infected men receiving poorly
      suppressive ART with acute urethritis for the presence of drug resistance
      associated mutations. In four men with gonorrhoea the blood and seminal plasma
      HIV-1 had mutations conferring reduced susceptibility to one or more available
      drugs. In one of these men the viral load of drug-resistant virus in seminal
      plasma was 20-fold higher during gonorrhoea than following antibiotic treatment,
      with no change in blood plasma viral load. We conclude that in the presence of
      suboptimal ART, sexually transmitted infections may enhance the spread of drug
      resistant HIV-1.

PMID- 14640397
TI  - Uridine excess does not interfere with the antiretroviral efficacy of nucleoside
      analogue reverse transcriptase inhibitors.

PMID- 14640398
TI  - Context-dependent sexual advertisement: plasticity in development of sexual
      ornamentation throughout the lifetime of a passerine bird.
AB  - Male investment into sexual ornamentation is a reproductive decision that depends
      on the context of breeding and life history state. In turn, selection for state-
      and context-specific expression of sexual ornamentation should favour the
      evolution of developmental pathways that enable the flexible allocation of
      resources into sexual ornamentation. We studied lifelong variation in the
      expression and condition-dependence of a sexual ornament in relation to age and
      the context of breeding in male house finches (Carpodacus mexicanus)--a species
      that develops a new sexual ornament once a year after breeding. Throughout males'
      lifetime, the elaboration of ornamentation and the allocation of resources to the
      development of sexual ornamentation depended strongly on pairing status in the
      preceding breeding season--males that were single invested more resources into
      sexual ornamentation and changed ornamentation more than males that were paired.
      During the initial (post-juvenile) moult, the expression of ornamentation was
      closely dependent on individual condition, however the condition-dependence of
      ornamentation sharply decreased throughout a male's lifetime and in older males
      expression of sexual ornamentation was largely independent of condition during
      moult. Selection for early breeding favoured greater ornamentation in males that
      were single in the preceding seasons and the strength of this selection increased
      with age. On the contrary, the strength of selection on sexual ornamentation
      decreased with age in males that were paired in the preceding breeding season.
      Our results reveal strong context-dependency in investment into sexual
      ornamentation as well as a high flexibility in the development of sexual
      ornamentation throughout a male's life.

PMID- 14640399
TI  - Association with host mitochondrial haplotypes suggests that feminizing
      microsporidia lack horizontal transmission.
AB  - The amphipod crustacean Gammarus duebeni hosts two feminizing microsporidian
      parasites, Nosema granulosis and Microsporidium sp. Samples of G. duebeni were
      collected from three sites on the Scottish island of Great Cumbrae and screened
      for microsporidia using polymerase chain reaction. Associations between the
      prevalence of the two feminizing parasites and haplotypes of the host
      mitochondrial gene cytochrome oxidase I (COI) were investigated. The prevalence
      of both parasites varied significantly among the host's COI haplotypes,
      suggesting that horizontal transmission is rare or absent in the life cycles of
      the feminizing microsporidia and that all transmission must therefore be
      vertical. Life cycles in which all transmission is vertical are common among
      bacterial parasites but have never before been demonstrated in Eukaryotic
      parasites.

PMID- 14640401
TI  - Flexible mating: cross-pollination affects sex-expression in a marine clonal
      plant.
AB  - Many functionally hermaphroditic plants have evolved mechanisms to reduce
      interference between the sex functions and to optimize reproductive output. In
      addition to physical mechanisms such as the spatial (herkogamy) and temporal
      (dichogamy) separation of male and female functions, plasticity in sex expression
      by means of mate-recognition (flexible mating) could be important in plants with
      variable access to cross-pollen. This applies particularly to clonal plants
      because of their modular growth form. We experimentally tested for the effects of
      pollen source and vegetative neighbourhood on instantaneous sex ratio and seed
      production in the self-compatible clonal marine angiosperm Zostera marina L. To
      this end, we exposed the (monoecious) flowering shoots to self and cross-pollen
      and to neighbourhoods of their own and a mix of foreign vegetative shoots.
      Flowering shoots that had been exposed to cross-pollen showed (1) a significantly
      lower female/male ratio at peak flowering, evidence for mate-recognition, and (2)
      a significantly higher seed set by the end of the season. Both effects were
      independent of the genetic composition of their vegetative neighbourhood. The
      results suggest that Z. marina maintains a cryptic self-incompatibility system
      not previously described for angiosperms with sub-aqueous pollination. In Z.
      marina, and possibly other self-compatible clonal plant species, mate-recognition
      could be a means of increasing the out-crossing probability for flowering shoots
      with central positions within their clone.

PMID- 14640400
TI  - Evolution of cultural communication systems: the coevolution of cultural signals
      and genes encoding learning preferences.
AB  - In several communication systems that rely on social learning, such as bird song,
      and possibly human language, the range of signals that can be learned is limited
      by perceptual biases--predispositions--that are presumably based on genes. In
      this paper, we examine the coevolution of such genes with the culturally
      transmitted communication traits themselves, using deterministic population
      genetic models. We argue that examining how restrictive genetic predispositions
      are is a useful way of examining the evolutionary origin and maintenance of
      learning. Under neutral cultural evolution, where no cultural trait has any
      inherent advantage over another, there is selection in favour of less restrictive
      genes (genes that allow a wider range of signals to recognized). In contrast,
      cultural conformity (where the most common cultural trait is favoured) leads to
      selection in favour of more restrictive genes.

PMID- 14640402
TI  - Large size in an island-dwelling bird: intraspecific competition and the
      Dominance Hypothesis.
AB  - Differences between island- and mainland-dwelling forms provide several classic
      ecological puzzles. Why, for instance, are island-dwelling passerine birds
      consistently larger than their mainland counterparts? We examine the 'Dominance
      hypothesis', based on intraspecific competition, which states that large size in
      island passerines evolves through selection for success in agonistic encounters.
      We use the Heron Island population of Capricorn silvereyes (Zosterops lateralis
      chlorocephalus), a large-bodied island-dwelling race of white-eye (Zosteropidae),
      to test three assumptions of this hypothesis; that (i) large size is positively
      associated with high fitness, (ii) large size is associated with dominance, and
      (iii) the relationship between size and dominance is particularly pronounced
      under extreme intraspecific competition. Our results supported the first two of
      these assumptions, but provided mixed evidence on the third. On balance, we
      suggest that the Dominance Hypothesis is a plausible mechanism for the evolution
      of large size of island passerines, but urge further empirical tests on the role
      of intraspecific competition on oceanic islands versus that on mainlands.

PMID- 14640403
TI  - Genetic architecture of susceptibility to herbivores in hybrid willows.
AB  - We performed a common garden experiment using parental, F1, F2, and backcross
      willow hybrids to test the hypothesis that hybrid willows experience breakdown of
      resistance to herbivores. After exposing plants to herbivores in the field, we
      measured the densities/damage caused by 13 insect herbivores and one herbivorous
      mite. Using joint-scaling tests, we determined the contribution of additive,
      dominance, and epistasis to variation in susceptibility to herbivores (measured
      either as density or damage level) among the six genetic classes. We found the
      genetic architecture of susceptibility/resistance in the parental species to be
      complex, involving additive, dominance, and epistasis for each herbivore species.
      Although genic interactions altered plant susceptibility for each of the 14
      herbivores, three distinct patterns of response of herbivores to hybrids were
      expressed. One pattern, observed in four herbivore species, supported the
      hypothesis of breakdown of resistance genes in recombinant hybrids. A second
      pattern, shown by six other herbivore species, supported the hypothesis of hybrid
      breakdown of host recognition genes. In other words, epistatic interactions for
      host recognition traits (probably oviposition/feeding stimulants or attractants)
      appeared to be important in determining herbivore abundance for those six
      species. The final patterns supported a structure of dominance, either for host
      recognition traits (in the case of three herbivore species) or for host
      resistance traits (for one herbivore species). The combination of differing
      responses of herbivore species, including members of the same genus and tribe,
      and the ubiquitous importance of epistasis suggests that many genes affect
      herbivore resistance in this hybrid willow system.

PMID- 14640404
TI  - Humoral immune response in relation to senescence, sex and sexual ornamentation
      in the barn swallow (Hirundo rustica).
AB  - Performance of animals may decline with age. The effects of senescence, however,
      may differ between the sexes because of differences in physiology and behaviour.
      Acquired immunity provides hosts with efficient mechanisms of anti-parasite
      defence, but the effect of senescence on immunocompetence has never been studied
      in natural populations. In the barn swallow (Hirundo rustica), primary antibody
      response to an antigen during one breeding season declined with age in females,
      while secondary response during the following breeding season declined with age
      in both sexes. Parasite-mediated sexual selection theory posits that male
      secondary sexual characters reveal resistance to parasites. Males with large tail
      ornaments had stronger primary response, retained larger antibody levels until
      the following year, but did not differ in secondary response compared with short
      tailed males, as predicted if ornamentation reflects resistance to parasites.
      This is the first study showing that immunocompetence declines with age in any
      vertebrate under natural conditions.

PMID- 14640405
TI  - Evidence for bimodal hybrid zones between two species of char (Pisces:
      Salvelinus) in northwestern North America.
AB  - Dolly Varden (Salvelinus malma, Pisces: Salmonidae) and bull trout (Salvelinus
      confluentus) have widely overlapping, but largely parapatric ranges in watersheds
      in northwestern North America from Washington State to northern British Columbia.
      Genetic analysis of natural populations using diagnostic molecular markers
      revealed widespread local sympatry and hybridization with hybrids comprising 0
      25% of the local samples. In a detailed analysis of hybridization using four
      nuclear DNA markers and mitochondrial DNA within the Thutade Lake watershed,
      northcentral British Columbia, hybrid genotypes constituted up to 9% of the
      population of juvenile char. There were significant deviations from Hardy
      Weinberg, gametic, and cytonuclear equilibria, and local samples showed bimodal
      frequency distributions of genotypes. Pure parental and inferred backcross
      genotypes were most common, and F1 and F(n) hybrids were comparatively rare.
      Interspecific hybridization was asymmetrical, with most F1 hybrids (five of six)
      bearing S. confluentus mtDNA. The introgression of nuclear and mitochondrial
      alleles was asymmetrical, with S. confluentus mtDNA and Growth Hormone 2
      introgressing into S. malma significantly more than either introgression of the
      three other nuclear loci, or introgression of S. malma alleles into S.
      confluentus. Substantial prezygotic isolation between the species likely depends
      on the large body size difference between them in sympatry: S. malma have small
      bodies and a stream resident life history (12-21 cm adult fork length at
      maturity), while S. confluentus are larger and adfluvial, i.e., they migrate to
      Thutade Lake where they grow to maturity before returning to tributary streams to
      spawn (40-90 cm at maturity). These traits may limit interspecific pairings
      because of size assortative pairing and size-dependent reproductive habitat use.

PMID- 14640406
TI  - Discord in the family Sparidae (Teleostei): divergent phylogeographical patterns
      across the Atlantic-Mediterranean divide.
AB  - The Strait of Gibraltar has been proposed to be the divide between two marine
      biogeographical regions, the Mediterranean Sea and the Northeast Atlantic.
      Intraspecific studies have shown, for several of the examined species, a
      reduction of gene flow between the two basins. The present study examines genetic
      variation at nuclear and mitochondrial loci in five marine teleost species
      belonging to the family Sparidae. Four samples for each species were analysed
      spanning the Northeast Atlantic and the Mediterranean. For all individuals 17
      allozyme loci were scored and a combined single strand conformation polymorphism
      sequencing approach was used to survey approximately 190 bp of the mitochondrial
      DNA (mtDNA) D-loop region. All five species share similar biological features.
      For three species, namely Lithognathus mormyrus, Spondyliosoma cantharus, and
      Dentex dentex, large mtDNA divergence was observed between Atlantic and
      Mediterranean samples. Little or no mtDNA differentiation was found in the other
      two species, Pagrus pagrus and Pagellus bogaraveo. Allozyme data revealed strong
      differentiation when comparing Atlantic and Mediterranean samples of L. mormyrus
      and D. dentex, moderate for P. pagrus, and no differentiation for P. bogaraveo
      and S. cantharus. These results provide evidence for a sharp phylogeographical
      break (sensu Avise) between the Atlantic and the Mediterranean for two (or
      possibly three) sparid species of the five investigated. At the same time, the
      obtained results for the other two species raise the question on which
      ecological/historical factors might have caused the observed discrepancy in the
      geographical distribution of genetic variation among otherwise biologically
      similar species.

PMID- 14640407
TI  - Temperature dependent larval resource allocation shaping adult body size in
      Drosophila melanogaster.
AB  - Geographical variation in Drosophila melanogaster body size is a long-standing
      problem of life-history evolution. Adaptation to a cold climate invariably
      produces large individuals, whereas evolution in tropical regions result in small
      individuals. The proximate mechanism was suggested to involve thermal evolution
      of resource processing by the developing larvae. In this study an attempt is made
      to merge proximate explanations, featuring temperature sensitivity of larval
      resource processing, and ultimate approaches focusing on adult and pre-adult life
      history traits. To address the issue of temperature dependent resource allocation
      to adult size vs. larval survival, feeding was stopped at several stages during
      the larval development. Under these conditions of food deprivation, two temperate
      and two tropical populations reared at high and low temperatures produced
      different adult body sizes coinciding with different probabilities to reach the
      adult stage. In all cases a phenotypic trade-off between larval survival and
      adult size was observed. However, the underlying pattern of larval resource
      allocation differed between the geographical populations. In the temperate
      populations larval age but not weight predicted survival. Temperate larvae did
      not invest accumulated resources in survival, instead they preserved larval
      biomass to benefit adult weight. In other words, larvae from temperate
      populations failed to re-allocate accumulated resources to facilitate their
      survival. A low percentage of the larvae survived to adulthood but produced
      relatively large flies. Conversely, in tropical populations larval weight but not
      age determined the probability to reach adulthood. Tropical larvae did not invest
      in adult size, but facilitated their own survival. Most larvae succeeded in
      pupating but then produced small adults. The underlying physiological mechanism
      seemed to be an evolved difference in the accessibility of glycogen reserves as a
      result of thermal adaptation. At low rearing temperatures and in the temperate
      populations, glycogen levels tended to correlate positively with adult size but
      negatively with pupation probability. The data presented here offer an
      explanation of geographical variation in body size by showing that thermal
      evolution of resource allocation, specifically the ability to access glycogen
      storage, is the proximate mechanism responsible for the life-history trade-off
      between larval survival and adult size.

PMID- 14640408
TI  - Conflicting selection pressures on seed size: evolutionary ecology of fruit size
      in a bird-dispersed tree, Olea europaea.
AB  - Recent evidence indicates that fruit size has evolved according to dispersers'
      size. This is hypothesized to result from a balance between factors favouring
      large seeds and dispersers setting the maximum fruit size. This hypothesis
      assumes that (1) the size of fruits that can be consumed by dispersers is
      limited, (2) fruit and seed size are positively correlated, and (3) the result of
      multiple selection pressures on seed size is positive. Our studies on the seed
      dispersal mutualism of Olea europaea have supported the first and second
      assumptions, but valid tests of the third assumption are still lacking. Here we
      confirm the third assumption. Using multiplicative fitness components, we show
      that conflicting selection pressures on seed size during and after dispersal
      reverse the negative pattern of selection exerted by dispersers.

PMID- 14640409
TI  - Sex choice in plants: facultative adjustment of the sex ratio in the perennial
      herb Begonia gracilis.
AB  - Sex allocation theory predicts that reproducing individuals will increase their
      fitness by facultatively adjusting their relative investment towards the rarer
      sex in response to population shifts in operational sex ratio (OSR). The
      evolution of facultative manipulation of sex ratio depends on the ability of the
      parents to track the conditions favouring skewed sex allocation and on the
      mechanism controlling sex allocation. In animals, which have well-developed
      sensorial mechanisms, facultative adjustment of sex ratios has been demonstrated
      on many occasions. In this paper, we show that plants have mechanisms that allow
      them to evaluate the population OSR. We simulated three different conditions of
      population OSR by manipulating the amount of pollen received by the female
      flowers of a monoecious herb, and examined the effect of this treatment on the
      allocation to male vs. female flowers. A shortage of pollen on the stigmas
      resulted in a more male-skewed sex allocation, whereas plants that experienced a
      relatively pollen rich environment tended to produce a more female-skewed sex
      allocation pattern. Our results for Begonia gracilis demonstrate that the
      individuals of this species are able to respond to the levels of pollination
      intensity experienced by their female flowers and adjust their patterns of sex
      allocation in accordance to the expectations of sex allocation theory.

PMID- 14640410
TI  - Foundress re-emergence and fig permeability in fig tree-wasp mutualisms.
AB  - Some female pollinating fig wasps (foundresses) re-emerge from figs after
      oviposition/pollination. We investigated why this occurs in the mutualism between
      the gynodioecious Ficus montana and Liporrhopalum tentacularis. Re-emergence
      increased with foundress density in figs and some foundresses oviposited in two
      male figs, indicating that they re-emerge because of oviposition site limitation.
      Re-emergence was independent of fig diameter, indicating that permeability is not
      because of fig age at entry. Rather, as some foundresses also pollinate two
      female figs we suggest permeability is selected for because it increases
      pollinator production and/or efficiency (although, potentially opposing these
      hypotheses, we also found between-tree differences in permeability in male figs).
      In addition, we show that re-emergence is much more common than previously
      suspected, and more common from gynodioecious than monoecious fig species. We
      argue that our findings in F. montana could explain this pattern of incidence.

PMID- 14640411
TI  - Determinants of sperm transfer in the scorpionfly Panorpa cognate: male
      variation, female condition and copulation duration.
AB  - Recent studies suggest that sperm production and transfer may have significant
      costs to males. Male sperm investment into a current copulation may therefore
      influence resources available for future matings, which selects for male
      strategic mating investment. In addition, females may also benefit from actively
      or passively altering the number of sperm transferred by males. In the
      scorpionfly Panorpa cognata, the number of sperm transferred during copulation
      depended on copulation duration and males in good condition (residual weight)
      copulated longer and also transferred more sperm. Moreover, sperm transferred and
      stored per unit time was higher in copulations with females in good condition
      than in copulations with females in poor condition. Males varied greatly and
      consistently in their sperm transfer rate, indicative of costs associated with
      this trait. The duration of the pairing prelude also varied between males and
      correlated negatively with the male's sperm transfer rate, but no other male
      character correlated significantly with male sperm transfer rate. The results are
      consistent with strategic mating effort but sperm transfer could also be
      facilitated by the physical size of females and/or females in good condition may
      be more cooperative during sperm transfer.

PMID- 14640412
TI  - Age-related decline in humoral immune function in Collared Flycatchers.
AB  - Although immune function usually declines with age in humans and captive animals,
      little is known about whether immune function deteriorates with age in natural
      populations. Here we present evidence for such an age-related deterioration in
      humoral immune function from a wild population of the Collared Flycatcher
      (Ficedula albicollis). In this study, young (1-year old), mid-age (3-year old)
      and old (5-6-year old) females were challenged with a nonpathogenic antigen,
      sheep red blood cells (SRBC), while provisioning their nestlings. The level of
      antibodies against SRBC was measured thereafter. Old females showed markedly
      lower humoral immune response and produced fledglings of lower body mass in
      comparison with the other two age classes. Moreover, the age classes differed in
      the relationship between immune response and fledgling body mass with mid-age
      females showing a significant positive relationship while the relationship was
      negative but nonsignificant among young and old females. The results are
      discussed in light of existing theories of optimal resource allocation, ageing
      and the theory of terminal investment.

PMID- 14640413
TI  - Environment-dependent inbreeding depression in a hermaphroditic freshwater snail.
AB  - Inbreeding depression was simultaneously studied under contrasted environments,
      laboratory and natural conditions, using individuals originating from 14 families
      of the freshwater snail Physa acuta. Both survival and growth of juveniles showed
      inbreeding depression under laboratory conditions. The same fitness components
      were monitored with mature snails either kept under laboratory conditions or
      released at a natural site and analysed using capture-mark-recapture models.
      Genetic composition of both samples was similar. Inbreeding depression on
      survival was highest in the laboratory while strong outbreeding depression was
      revealed in the field. Thus inbreeding depression may not be always higher under
      natural conditions, at the opposite of what is commonly assumed. We suggest that
      inbreeding depression is dependent on metabolic requirements imposed by the
      environment. Other evidences showing that inbreeding depression is environment
      dependent are reviewed. We conclude that genetic models should include both
      genetic and environmental variance in inbreeding depression for studying mating
      system evolution.

PMID- 14640414
TI  - Patterns of epistasis in RNA viruses: a review of the evidence from vaccine
      design.
AB  - Epistasis results when the fitness effects of a mutation change depending on the
      presence or absence of other mutations in the genome. The predictions of many
      influential evolutionary hypotheses are determined by the existence and form of
      epistasis. One rich source of data on the interactions among deleterious
      mutations that has gone untapped by evolutionary biologists is the literature on
      the design of live, attenuated vaccine viruses. Rational vaccine design depends
      upon the measurement of individual and combined effects of deleterious mutations.
      In the current study, we have reviewed data from 29 vaccine-oriented studies
      using 14 different RNA viruses. Our analyses indicate that (1) no consistent
      tendency towards a particular form of epistasis exists across RNA viruses and (2)
      significant interactions among groups of mutations within individual viruses
      occur but are not common. RNA viruses are significant pathogens of human disease,
      and are tractable model systems for evolutionary studies--we discuss the
      relevance of our findings in both contexts.

PMID- 14640415
TI  - A molecular phylogeny of enteric bacteria and implications for a bacterial
      species concept.
AB  - A molecular phylogeny for seven taxa of enteric bacteria (Citrobacter freundii,
      Enterobacter cloacae, Escherichia coli, Hafnia alvei, Klebsiella oxytoca,
      Klebsiella pneumoniae, and Serratia plymuthica) was made from multiple isolates
      per taxa taken from a collection of environmental enteric bacteria. Sequences
      from five housekeeping genes (gapA, groEL, gyrA, ompA, and pgi) and the 16S rRNA
      gene were used to infer individual gene trees and were concatenated to infer a
      composite molecular phylogeny for the species. The isolates from each taxa formed
      tight species clusters in the individual gene trees, suggesting the existence of
      'genotypic' clusters that correspond to traditional species designations. These
      sequence data and the resulting gene trees and consensus tree provide the first
      data set with which to assess the utility of the recently proposed core genome
      hypothesis (CGH). The CGH provides a genetically based approach to applying the
      biological species concept to bacteria.

PMID- 14640416
TI  - Effects of food abundance on genetic and maternal variation in the growth rate of
      juvenile red squirrels.
AB  - Sources of variation in growth in body mass were assessed in natural and
      experimental conditions of high and low food abundance using reciprocal cross
      fostering techniques and long-term data (1987-2002) for a population of North
      American red squirrels (Tamiasciurus hudsonicus). Growth rates were significantly
      higher in naturally good and food supplemented conditions, than in poor
      conditions. Mother-offspring resemblance was higher in poor conditions as a
      result of large increases in both the direct genetic variance and direct-maternal
      genetic covariance and a smaller increase in the coefficient of maternal
      variation. Furthermore, the genetic correlation across environments was
      significantly less than one indicating that sources of heritable variation
      differed between the two environments. These results are consistent with the
      hypothesis that selection has eroded heritable variation for growth more in good
      conditions and indicate the potential for independent adaptation of growth rates
      in good and poor conditions.

PMID- 14640417
TI  - Migratory costs and contemporary evolution of reproductive allocation in male
      chinook salmon.
AB  - Energetically demanding migrations may impact the resources available for
      reproductive trait development and activity, and hence favour evolution of new
      investment strategies for remaining resources. We conducted a large-scale
      experiment to evaluate the proximate cost of migration on male reproductive
      investment in chinook salmon (Oncorhynchus tshawytscha) and contemporary
      evolution of reproductive allocation. Experimentally induced differences in
      migratory costs (17 km inland and 17 m elevation vs. 100 km and 430 m) influenced
      dorsal hump size and upper jaw length, two traits influencing male mating success
      that are developed during migration. Longer migration also reduced tissue energy
      reserves available for competition and length of breeding life. Corresponding
      shifts in the balance between natural and sexual selection appear to have been
      responsible for heritable population divergence in secondary sexual trait
      investment, in approximately 26 generations, following colonization of spawning
      sites with different migratory demands.

PMID- 14640418
TI  - Relationship between fluctuating asymmetry and fitness within and between
      stressed and unstressed populations of the wolf spider Pirata piraticus.
AB  - Although developmental instability, measured as fluctuating asymmetry (FA), is
      expected to be positively related to stress and negatively to fitness, empirical
      evidence is often lacking or contradictory when patterns are compared at the
      population level. We demonstrate that two important properties of stressed
      populations may mask such relationships: (i) a stronger relationship between FA
      and fitness, resulting in stronger selection against low quality (i.e.
      developmental unstable) individuals and (ii) the evolution of adaptive responses
      to environmental stress. In an earlier study, we found female wolf spiders Pirata
      piraticus from metal exposed populations to be characterized by both reduced
      clutch masses and increased egg sizes, the latter indicating an adaptive response
      to stress. By studying the relationship between these two fitness related traits
      and levels of FA at individual level, we here show a significant negative
      correlation between FA and clutch mass in metal stressed populations but not in
      unstressed reference populations. As a result, levels of population FA may be
      biased downward under stressful conditions because of the selective removal of
      developmentally unstable (low quality) individuals. We further show that females
      that produced larger eggs in stressed populations exhibited lower individual FA
      levels. Such interaction between individual FA and fitness with stress may
      confound the effect of metal stress on FA, resulting in an absence of
      relationships between FA, fitness and stress at the population level.

PMID- 14640419
TI  - Evolutionary history of asexual hybrid loaches (Cobitis: Teleostei) inferred from
      phylogenetic analysis of mitochondrial DNA variation.
AB  - Reconstruction of the evolutionary history of asexual lineages undermines their
      suitability as models for the studies of evolutionary consequences of sexual
      reproduction. Using molecular tools we addressed the origin, age and maternal
      ancestry of diploid and triploid asexual lineages arisen through the
      hybridization between spiny loaches Cobitis elongatoides, C. taenia and C.
      tanaitica. Reconstructions of the phylogenetic relationships among mitochondrial
      DNA (mtDNA) haplotypes, revealed by sequence analyses, suggest that both hybrid
      complexes (C. elongatoides-taenia and C. elongatoides-tanaitica) contained
      several asexual lineages of independent origin. Cobitis elongatoides was the
      exclusive maternal ancestor of all the C. elongatoides-tanaitica hybrids, whereas
      within the C. elongatoides-taenia complex, hybridization was reciprocal. In both
      complexes the low haplotype divergences were consistent with a recent origin of
      asexual lineages. Combined mtDNA and allozyme data suggest that the triploids
      arose through the incorporation of a haploid sperm genome into unreduced ova
      produced by diploid hybrids.

PMID- 14640420
TI  - Sire coloration influences offspring survival under predation risk in the
      moorfrog.
AB  - When breeding, male moor frogs Rana arvalis develop a bright blue dorsal
      coloration which varies in intensity between males. We tested whether this colour
      acts as a potential signal of a male's genetic quality to female moor frogs by
      artificially crossing pairs of males differing in the extent of the blue
      coloration to the same female. Maternal half-sibships provide a powerful means to
      detect paternal genetic effects on offspring as they control for other
      potentially confounding variables. We assayed the ability of offspring to survive
      an ecologically realistic test of fitness by exposing them to predation by the
      larvae of the predatory water beetle Dytiscus marginalis. Although sire's
      coloration did not influence tadpole body size, it did affect their ability to
      survive the predation trial. Offspring of bright blue males had higher survival
      than those of dull males when exposed to large predators, which were more
      voracious predators than smaller ones. Our results indicate that paternal
      secondary sexual traits provide information about genetic effects on offspring
      fitness in this species, but suggest that these effects may be context-dependent.
      Variable selection caused by contextual dependence may have important
      consequences for the evolution of female choice rules, and for the maintenance of
      genetic variation for both male trait and female preference.

PMID- 14640421
TI  - Sexual variation in heritability and genetic correlations of morphological traits
      in house sparrow (Passer domesticus).
AB  - Estimates of genetic components are important for our understanding of how
      individual characteristics are transferred between generations. We show that the
      level of heritability varies between 0.12 and 0.68 in six morphological traits in
      house sparrows (Passer domesticus L.) in northern Norway. Positive and negative
      genetic correlations were present among traits, suggesting evolutionary
      constraints on the evolution of some of these characters. A sexual difference in
      the amount of heritable genetic variation was found in tarsus length, wing
      length, bill depth and body condition index, with generally higher heritability
      in females. In addition, the structure of the genetic variance-covariance matrix
      for the traits differed between the sexes. Genetic correlations between males and
      females for the morphological traits were however large and not significantly
      different from one, indicating that sex-specific responses to selection will be
      influenced by intersexual differences in selection differentials. Despite this,
      some traits had heritability above 0.1 in females, even after conditioning on the
      additive genetic covariance between sexes and the additive genetic variances in
      males. Moreover, a meta-analysis indicated that higher heritability in females
      than in males may be common in birds. Thus, this indicates sexual differences in
      the genetic architecture of birds. Consequently, as in house sparrows, the
      evolutionary responses to selection will often be larger in females than males.
      Hence, our results suggest that sex-specific additive genetic variances and
      covariances, although ignored in most studies, should be included when making
      predictions of evolutionary changes from standard quantitative genetic models.

PMID- 14640422
TI  - Correlated evolution of colour pattern and body size in polymorphic pygmy
      grasshoppers, Tetrix undulata.
AB  - Theory posits that selection on functionally interrelated characters will promote
      physical and genetic integration resulting in evolution of favourable trait-value
      combinations. The pygmy grasshopper Tetrix undulata (Orthoptera: Tetrigidae)
      displays a genetically encoded polymorphism for colour pattern. Colour morphs
      differ in several traits, including behaviours, thermal biology and body size. To
      examine if these size differences may reflect phenotypic plasticity of growth and
      development in response to temperature we used a split brood-design and reared
      hatchlings from mothers belonging to different morphs in different thermal
      environments (warm or cold) until maturity. We found that time to maturity was
      longer in the cold compared with the warm treatment. In the warm (but not in the
      cold) treatment time to maturity also varied among individuals born to mothers
      belonging to different colour morphs. Although low temperature and long
      development time are normally accompanied by increased body size in ectotherms,
      our results revealed no difference in size at maturity between individuals reared
      in the two temperature treatments. There was also an increase (not a decrease) in
      adult body size with shortened time to maturity across families within each
      treatment. Taken together, this suggests that body size is canalized against
      environmental perturbations, and that early maturation does not necessarily trade
      off against a size-mediated decrease in fecundity. Heritability of body size was
      moderate in magnitude. Moreover, body size at maturity varied among individuals
      belonging to different morphs and was influenced also by maternal colour morph,
      suggesting that a genetic correlation exists between colour pattern and body
      size. These findings suggest that different characters have evolved in concert
      and that the various colour morphs represent different evolutionary strategies,
      i.e., alternative peaks in a multi-modal adaptive landscape.

PMID- 14640423
TI  - Defence against multiple enemies.
AB  - Although very common under natural conditions, the consequences of multiple
      enemies (parasites, predators, herbivores, or even 'chemical' enemies like
      insecticides) on investment in defence has scarcely been investigated. In this
      paper, we present a simple model of the joint evolution of two defences targeted
      against two enemies. We illustrate how the respective level of each defence can
      be influenced by the presence of the two enemies. Furthermore, we investigate the
      influences of direct interference and synergy between defences. We show that,
      depending on certain conditions (costs, interference or synergy between
      defences), an increase in selection pressure by one enemy can have dramatic
      effects on defence against another enemy. It is generally admitted that
      increasing the encounter rate with a second natural enemy can decrease investment
      in defence against a first enemy, but our results indicate that it may sometimes
      favour resistance against the first enemy. Moreover, we illustrate that the
      global defence against one enemy can be lower when only this enemy is present:
      this has important implications for experimental measures of resistance, and for
      organisms that invade an area with less enemies or whose community of enemies is
      reduced. We discuss possible implications of the existence of multiple enemies
      for conservation biology, biological control and chemical control.

PMID- 14640424
TI  - Multiple paternity and population genetic structure in natural populations of the
      poeciliid fish, Heterandria formosa.
AB  - Heterandria formosa Agassiz, exhibits internal fertilization, internal brooding
      of embryos, sperm storage and an extreme level of superfetation. In this study we
      used microsatellite markers to examine variation among seven populations that
      exhibited significant variance in their histories of population density. We found
      that the populations were genetically distinct and that the heterozygosity
      increased as population density increased. We also examined paternity in three of
      those populations and found that the number of sires per female and the number of
      sires per brood increased with population density. Overall, the rates of multiple
      paternity are quite low relative to other species. The correlations with
      population density suggest that contact rates play a critical role in the
      breeding system in this species but the low rates of multiple paternity suggest
      that females may exert control over fertilization of their ova.

PMID- 14640425
TI  - Coevolution between hosts and parasites with partially overlapping geographic
      ranges.
AB  - Many host species interact with a specific parasite within only a fraction of
      their geographical range. Where host and parasite overlap geographically,
      selection may be reciprocal constituting a coevolutionary hot spot. Host
      evolution, however, may be driven primarily by selection imposed by alternative
      biotic or abiotic factors that occur outside such hot spots. To evaluate the
      importance of coevolutionary hot spots for host and parasite evolution, we
      analyse a spatially explicit genetic model for a host that overlaps with a
      parasite in only part of its geographical range. Our results show that there is a
      critical amount of overlap beyond which reciprocal selection leads to a
      coevolutionary response in the host. This critical amount of overlap depends upon
      the explicit spatial configuration of hot spots. When the amount of overlap
      exceeds this first critical level, host-parasite coevolution commonly generates
      stable allele frequency clines rather than oscillations. It is within this region
      that one of the primary predictions of the geographic mosaic theory is realized,
      and local maladaptation is prevalent in both species. Past a further threshold of
      overlap between the species oscillations do evolve, but allele frequencies in
      both species are spatially synchronous and local maladaptation is absent in both
      species. A consequence of such transitions between coevolutionary dynamics is
      that parasite adaptation is inversely proportional to the fraction of its host's
      range that it occupies. Hence, as the geographical range of a parasite increases,
      it becomes increasingly maladapted to the host. This suggests a novel mechanism
      through which the geographical range of parasites may be limited.

PMID- 14640426
TI  - Electron microscopy of surface smoothness of porcine corneas and acrylic plates
      with four brands of excimer laser.
AB  - PURPOSE: This study compares ablation smoothness patterns produced on four
      different excimer laser devices available for photorefractive surgery. METHODS:
      VISX calibration plastic and porcine cornea were ablated with standard -3.00-D, 
      6.00-D, and -9.00-D settings using four different excimer lasers: VISX S2 Smooth
      Scan, Nidek EC-5000, Autonomous Ladar Vision System, and Bausch and Lomb
      Technolas. Electron microscopy and laser interferometry were used for qualitative
      evaluation of the ablated surfaces. Corneal ablation surface smoothness was
      graded by ten independent observers. Calibration plastic ablated surfaces were
      evaluated quantitatively for smoothness by laser interferometry. RESULTS: The
      independent observer assessment of corneal ablation surface smoothness
      demonstrated that the Autonomous small spot Gaussian profile laser produced the
      smoothest ablation surfaces, followed by the other broad beam lasers. In
      comparing ablation smoothness among various refractive powers (-9.00 D, -6.00 D,
      and -3.00 D), a trend was observed that indicated a correlation of higher
      refractive settings with decreasing surface smoothness. However, this trend was
      not statistically significant. The quantitative laser interferometry measurements
      supported the independent observer ranking of the Autonomous flying small spot
      ablation profile as the smoothest. However, there were differences between the
      laser interferometry smoothness rankings and independent observer smoothness
      rankings. CONCLUSION: There were significant differences in ablation surface
      smoothness among the four excimer lasers tested.

PMID- 14640427
TI  - Ablation centration in laser in situ keratomileusis for hyperopia: comparison of
      VISX S3 ActiveTrak and VISX S2.
AB  - PURPOSE: To compare ablation centration and outcome measurements in laser in situ
      keratomileusis (LASIK) for hyperopia using the pupil-tracking VISX S3 ActiveTrak
      or the nontracking VISX S2 excimer laser. METHODS: In a retrospective study, 49
      consecutively treated hyperopic eyes (32 patients) that had LASIK by the VISX
      StarS3 ActiveTrak were compared to 49 control-matched eyes treated with the VISX
      StarS2 without pupil-tracking. Primary outcome variables including ablation
      centration, uncorrected visual acuity, best spectacle-corrected visual acuity,
      manifest refraction, complications, and induced cylinder analyzed by vector
      analysis were evaluated 3 months postoperatively. RESULTS: Hyperopic sphere
      ranged between plano and +5.50 D and cylinder between 0 and +2.75 D. Ninety-five
      of 98 eyes (96.9%) were available for analysis at 3 months. Of these 95, 52 eyes
      could be used for analysis of ablation centration. Mean decentration of the
      ablation zone from the entrance pupil was 0.30 +/- 0.20 mm in tracked eyes (n=31)
      and 0.41 +/- 0.39 mm in nontracked eyes (n=21), P=.17. Two eyes (6.5%) in the
      tracked group were significantly decentered between 0.5 and 1 mm from the pupil
      center. In the nontracked group, decentration was between 0.5 and 1 mm in one eye
      (4.8%) and greater than 1 mm in two eyes (9.5%). CONCLUSIONS: Comparable ablation
      centration in LASIK for hyperopia was achieved between actively-tracked and
      nontracked eyes. Decentrations (greater than 1 mm) were not seen with a tracking
      system in this study. Visual and refractive results were similar between the VISX
      StarS3 ActiveTrak and VISX StarS2 laser systems.

PMID- 14640428
TI  - Ocular surface management of photorefractive keratectomy and laser in situ
      keratomileusis.
AB  - PURPOSE: To examine the effects of keratorefractive surgery and ocular surface
      management on goblet cell density, dry eye symptom incidence, and spherical
      equivalent refraction. METHODS: We performed a retrospective analysis of four
      myopia groups: Untreated controls (n = 53); PRK (n = 51); LASIK without ocular
      surface management (n = 56); LASIK with ocular surface management (n = 140).
      Ocular surface management involved the routine use of non-preserved artificial
      tears and other lubricants before, during, and after surgery. Lid hygiene
      procedures, topical anti-inflammatory agents, and punctal plugs were used on
      indication. Assessments were conducted before and up to 12 months after surgery
      (right eyes only in patients with both eyes operated, and in the left or right
      eye in patients with one eye operated). RESULTS: Surgery caused a significant
      reduction in goblet cell density, with the greatest reduction in the LASIK
      without ocular surface management group. No significant differences were detected
      in dry eye symptoms or spherical equivalent refraction between PRK and LASIK
      without ocular surface management. Ocular surface management significantly
      minimized LASIK-induced decreases in goblet cell density and was associated with
      significantly less myopic outcomes at months 1 to 3 and 6 to 9 after LASIK. After
      surgery (1 to 3 mo), dry eye symptoms were significantly lower in the LASIK with
      ocular surface management group. In all groups, significant inverse correlations
      existed between goblet cell density and dry eye symptoms. CONCLUSIONS: Ocular
      surface management minimized the negative impact of LASIK on goblet cell density
      and reduced dry eye symptoms. Without ocular surface management, goblet cell
      density and dry eye symptoms after LASIK were similar to or worse than after PRK.

PMID- 14640429
TI  - Ferrara intrastromal corneal ring segments for severe keratoconus.
AB  - PURPOSE: Intrastromal Ferrara ring segments were inserted in eyes with severe
      keratoconus to evaluate safety and efficacy of this procedure. METHODS:
      Intrastromal Ferrara ring segments were placed in 36 eyes of 35 patients with
      severe keratoconus, who were evaluated after 12 months of follow-up. All patients
      had highly disabling visual acuity, contact lens intolerance, and a previous
      indication for penetrating keratoplasty. Statistical analysis included
      preoperative and postoperative uncorrected visual acuity, best spectacle
      corrected visual acuity, manifest refraction, anterior chamber depth,
      keratometry, and pachymetry. RESULTS: No patient had a loss of visual acuity.
      Uncorrected visual acuity improved in 28 eyes (77.78%) and best spectacle
      corrected visual acuity improved in 29 eyes (80.56%). Spherical equivalent
      refraction decreased from -7.29 +/- 3.12 D to -4.80 +/- 3.04 D at 12 months after
      Ferrara intrastromal ring segment implantation. Corneal topography and ultrasound
      biomicroscopy showed corneal flattening, demonstrated by thinning of the central
      cornea and a reduction in anterior chamber depth. Segment decentration occurred
      in one eye (2.7%), asymmetric positioning of the segments in two eyes (5%),
      inadequate depth in two eyes (5%), migration of the segments in two eyes (5%),
      segment extrusion in five eyes (13.8%), conjunctivitis in one eye (2.7%),
      bacterial keratitis in one eye (2.7%), and hydrops in one eye (2.7%).
      CONCLUSIONS: With these early results, Ferrara intrastromal ring segments appear
      to be an alternative for the treatment of severe keratoconus.

PMID- 14640430
TI  - Nomogram considerations with the Technolas 217A for treatment of myopia.
AB  - PURPOSE: To determine whether surgeon-specific nomogram adjustments are useful
      when using the Technolas 217A excimer laser for treating myopia and myopic
      astigmatism. METHODS: We conducted a prospective evaluation of 216 consecutive
      eyes with 6 months follow-up after treatment of myopia or myopic astigmatism with
      the Technolas 217A laser. Attempted vs. achieved change in refraction was
      analyzed with a statistical analysis software program. Factors such as age,
      corneal thickness (pachymetry), preoperative spherical equivalent refraction,
      preoperative cylinder, and optical zone were studied to evaluate their role in
      predicting refractive outcome at 6 months after LASIK. RESULTS: The mean value of
      attempted spherical equivalent refraction was -5.32 +/- 2.72 D. The mean achieved
      refractive correction at 6 months was -5.55 +/- 2.78 D, with a mean spherical
      equivalent of 0.13 +/- 0.54 D. The percent achieved effect at 1 month was 105%,
      and at 6 months, 103%. Preoperative spherical equivalent refraction and optical
      zone size were strong predictors of 6-month LASIK outcome. There was a 9%
      difference in the percent achieved effect between a 4 and 7-mm optical zone.
      There was no correlation between age, preoperative cylinder, or surgeon and 6
      month outcome. CONCLUSIONS: Surgeons using the planoscan software on the
      Technolas 217A may experience a small initial overcorrection. There may be a
      benefit to reducing the treatment given with larger optical zones and smaller
      corrections.

PMID- 14640431
TI  - Prophylactic laser photocoagulation for retinal breaks before laser in situ
      keratomileusis.
AB  - PURPOSE: To determine the efficacy and safety of prophylactic laser
      photocoagulation for retinal breaks in myopic patients undergoing laser in situ
      keratomileusis (LASIK). METHODS: Between August 1998 and August 2002, a total of
      1931 eyes in 1006 patients requesting LASIK received a fundus examination with
      indirect ophthalmoscopy before surgery. For analysis, patients were divided into
      two groups according to the presence or absence of retinal breaks. All patients
      with retinal breaks underwent prophylactic laser photocoagulation to seal the
      breaks, even though they were asymptomatic. RESULTS: Patient age ranged from 18
      to 68 years (30.8 +/- 7.4 yr). Mean preoperative spherical equivalent refraction
      was -7.55 +/- 3.72 D (range -1.87 to -34.50 D). Retinal breaks were identified
      and treated in 39 eyes (2.02%) of 32 patients (3.2%); 1892 eyes of 974 patients
      had no retinal breaks. No statistically significant difference was found in age
      (P=.87) or gender (P=.91) between the two groups. However, a significantly higher
      preoperative spherical equivalent refraction was noted in patients with retinal
      breaks (-9.41 +/- 4.15 D) compared with those without (-7.52 +/- 3.71 D)
      (P=.017). During a mean 19-month follow-up, none of the patients developed
      retinal detachment except for one in a patient without retinal breaks who
      sustained ocular trauma 19 months after LASIK. This patient was treated with
      scleral buckle and the retina was attached after surgery. CONCLUSIONS: Retinal
      breaks were identified and treated by photocoagulation in 2% of 1931 eyes before
      LASIK for myopia.

PMID- 14640432
TI  - Laser epithelial keratomileusis for myopia.
AB  - PURPOSE: To describe a new technique for excimer laser corneal surgery: laser
      epithelial keratomileusis (LASEK). METHODS: We report 76 eyes with spherical
      equivalent refractive myopia ranging from -8.00 to -22.00 D (mean -11.00 +/- 3.00
      D). Using ethanol applied over an 8.5-mm-diameter area for 20 seconds, the
      epithelium was detached and photorefractive keratectomy (PRK) was performed. The
      epithelium was reapplied to the ocular surface and covered with a therapeutic
      soft contact lens. Treatments were carried out with the Nidek EC-5000 excimer
      laser. RESULTS: At a mean of 803 days after LASEK, mean spherical equivalent
      refraction was -1.80 +/- 2.40 D (range -9.27 to +2.00 D). Stability was reached
      in approximately 60 days. Fifty-nine percent of the epithelial flaps were easy to
      detach intact during surgery and 62.7% of patients reported no postoperative
      pain. Eighty-four percent of eyes had the therapeutic bandage lens removed by the
      fourth postoperative day. Twelve percent of eyes had incomplete epithelial flap
      removal. Epithelium can fall off the cornea during the healing phase. No
      significant subepithelial haze was seen in 95% of eyes. CONCLUSION: With LASEK,
      it may be possible to treat a larger diameter ablation zone in thinner corneas
      without the problems of a LASIK stromal flap and with less postoperative pain
      than PRK, with minimal subepithelial haze.

PMID- 14640433
TI  - Peripheral keratitis following laser in situ keratomileusis.
AB  - PURPOSE: To report two different cases of sterile, peripheral keratitis following
      laser in situ keratomileusis (LASIK). METHODS: A report of two cases (two eyes of
      two patients). RESULTS: In two patients, peripheral infiltrates appeared 1 day
      after LASIK. One patient had a history of rheumatoid arthritis and both had
      peripheral corneal changes that may have represented prior inflammatory events.
      The presentations were quite different, with one occurring in association with an
      epithelial defect at the edge of the flap and the other occurring without an
      epithelial defect peripheral to the microkeratome cut. In the second case a
      similar infiltrate showed up in the unoperated fellow eye. Both patients were
      treated with aggressive antibiotic and corticosteroid therapy. Both patients
      recovered well with no loss of best spectacle-corrected visual acuity.
      CONCLUSION: Peripheral keratitis can occur in patients following LASIK;
      preoperative evidence of previous inflammation may be a marker for patients at
      higher risk. Rheumatoid arthritis patients may be at increased risk for this
      complication. With careful and aggressive management excellent visual outcomes
      are still possible.

PMID- 14640434
TI  - Relationship between cycloplegic and wavefront-derived refraction.
AB  - PURPOSE: To compare cycloplegic refractions to preoperative wavefront-derived
      refractions from three Hartmann-Shack-based wavefront devices. METHODS: Ninety
      nine eyes of 55 subjects were evaluated preoperatively using the LADARWave,
      WaveScan, and Zywave aberrometers. With cycloplegic refraction as the standard,
      the spherical equivalent refraction, sphere, and cylinder were compared to the
      wavefront-derived refractions using the three wavefront devices. RESULTS: The
      LADARWave unit showed the highest correlation between wavefront-derived sphere
      and mean spherical equivalent refraction values relative to cycloplegic
      refraction, followed by Zywave and WaveScan. The WaveScan unit exhibited higher
      variability than the LADARWave or Zywave. Although Alcon Laboratories (LADARWave)
      and Bausch & Lomb Surgical (Zywave) recommend dilation, VISX specifically
      recommends against dilation in their WaveScan unit. All devices showed high
      cylinder error vectors when the cycloplegic cylinder was greater than 1.00 D.
      CONCLUSION: Although wavefront-derived refractions appeared to correlate well to
      cycloplegic refractions, further research is required to reduce variability and
      improve the calculation of cylinder terms.

PMID- 14640435
TI  - Correlation of aberrations with visual symptoms using wavefront analysis in eyes
      after laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the information assessed with the Alcon LADARWave wavefront
      measurement device and correlate it with visual symptoms in eyes previously
      treated with laser in situ keratomileusis (LASIK), and to analyze the influence
      of scotopic pupil size on visual symptoms. METHODS: One hundred and five eyes of
      58 patients who underwent LASIK were evaluated. Wavefront measurements were
      assessed using the Alcon LADARWave device. Visual symptoms were correlated to
      higher order aberrations in three different pupil sizes (5 mm, 7 mm, and scotopic
      pupil size). Generalized estimating equations were used for statistical analysis.
      RESULTS: In eyes after LASIK, visual symptoms analysis showed positive
      correlation of double vision with total coma and with horizontal coma for the 5
      mm and 7-mm pupil sizes, negative correlation between starburst and total coma
      for the 7-mm pupil size, positive correlation of double vision with horizontal
      coma, and glare and starburst with spherical aberration and with total
      aberrations. Scotopic pupil size had a positive association with starburst and
      negative association with double vision. CONCLUSION: The LADARWave wavefront
      measurement device is a valuable diagnostic tool in measuring ocular aberrations
      in eyes after LASIK. A strong correlation between visual symptoms and ocular
      aberrations, such as monocular diplopia with coma, and starburst and glare with
      spherical aberration, suggest this device is valuable in diagnosing symptomatic
      LASIK-induced aberrations. Horizontal coma was correlated with double vision,
      while vertical coma was not, demonstrating a greater sensitivity with
      horizontally oriented multifocality.

PMID- 14640436
TI  - First 100 CustomCornea commercial eyes.
AB  - PURPOSE: With the advent of wavefront-guided custom abalation we not only try to
      reach a target of 20/20 vision, but strive for improvement in what has always
      been most important--the quality of this vision. METHODS AND RESULTS: Insights
      are presented, based on clinical experience at Durrie Vision with our first 100
      commercial CustomCornea eyes. We highlight key points for preparing a clinical
      practice for this new technology, such as staff training, marketing, and pricing.
      We discuss technical aspects such as patient selection and target adjustment as
      they relate to the Alcon LADARWave system. CONCLUSION: In our practice we have
      thus far had clinical success with CustomCornea; patient acceptance has been
      high, and by closely monitoring our first few patients we were able to reduce the
      number of future enhancements.

PMID- 14640437
TI  - Laser in situ keratomileusis with Alcon CustomCornea.
AB  - PURPOSE: To report the 3-month results of our first cases of laser in situ
      keratomileusis (LASIK) with Alcon's CustomCornea. METHODS: Wavefront analysis was
      performed using the LADARWave aberrometer and ablation was performed with the
      LADARVision4000 system. Thirty-one eyes of 17 patients were analyzed
      prospectively, at 1 and 3 months after CustomCornea surgery. Psychophysical tests
      were performed, including high and low contrast acuity, and contrast sensitivity
      under scotopic and photopic conditions. In addition, psychometric testing was
      performed using a subjective vision questionnaire. RESULTS: Mean spherical
      equivalent refraction improved from a baseline -3.05 +/- 1.92 D to +0.02 +/- 0.28
      D at 3 months (28 eyes). At 3 months, 46.4% (13 eyes) had uncorrected visual
      acuity of 20/16, 92.7% (26 eyes) had 20/20, and 100% (28 eyes) had 20/25
      uncorrected visual acuity. Three months after CustomCornea surgery, there was a
      statistically significant improvement in contrast sensitivity under both scotopic
      and photopic conditions, and a statistically significant increase in third and
      fourth order aberrations. There was a statistically significant improvement in
      visual quality as measured by the subjective vision index, increasing from a
      preoperative mean 66.62 to 87.63 at 3 months after surgery. CONCLUSIONS:
      CustomCornea was an improvement over conventional LASIK as measured by most
      psychophysical and psychometric parameters. The relationship between higher order
      aberrations and other psychophysical and psychometric measurements needs more
      analysis.

PMID- 14640438
TI  - Wavefront-guided treatment for previous laser in situ keratomileusis and
      photorefractive keratectomy: case reports.
AB  - PURPOSE: To describe the off-label use of the Alcon LADARVision System for
      CustomCornea (LADARWave and LADARVision4000) in two patients, one for retreatment
      after laser in situ keratomileusis (LASIK) and one for retreatment after
      photorefractive keratectomy (PRK). METHODS AND RESULTS: Both patients were
      unhappy with the quality of their vision after initial refractive surgery. The
      first patient initially had LASIK to correct -4.75 D of myopia in each eye, and
      then had retreatment with CustomCornea. Before retreatment, manifest refraction
      was OD 0.50 -0.50 x 180 degrees (20/25 uncorrected) and OS -0.50 -0.75 x 180
      degrees (20/40 uncorrected). Two months after retreatment with CustomCornea, his
      uncorrected visual acuity OD was 20/15, and 1 month after retreatment in his left
      eye, uncorrected visual acuity was 20/15. The second patient had PRK OD, with a
      postoperative uncorrected visual acuity of 20/25 and cycloplegic refraction of
      +1.00 -0.75 x 84 degrees. After CustomCornea retreatment, his 3.5-month
      postoperative uncorrected visual acuity was 20/15 and manifest refraction was
      +0.50 -0.50 x 180 degrees. CONCLUSION: The Alcon LADARVision System for
      CustomCornea was used effectively to retreat both a myopic LASIK and myopic PRK
      patient, primarily for subjective quality of night vision complaints.

PMID- 14640439
TI  - Wavefront-guided treatment of abnormal eyes using the LADARVision platform.
AB  - PURPOSE: To evaluate the clinical results of Alcon LADARVision4000 wavefront
      guided customized treatment of eyes with myopia and/or astigmatism, and
      clinically significant visual symptoms related to the presence of higher order
      aberrations. METHODS: Seven consecutive abnormal eyes from seven patients
      underwent wavefront-guided CustomCornea (1 PRK, 6 enhancements after previous
      LASIK) to correct low and higher order aberrations, using the Alcon
      LADARVision4000 platform. Eyes were examined at 1 to 3 months after treatment;
      the longest follow-up examination was used for analysis. Uncorrected and best
      spectacle-corrected visual acuity, manifest refractive spherical equivalent
      error, and subjective visual symptoms were measured, as well as wavefront
      measurement of higher order aberrations. RESULTS: All seven eyes had an
      improvement in UCVA. One eye gained 2 lines of BSCVA, four eyes gained 1 line,
      and no eye lost any lines. Manifest refractive spherical equivalent error was
      slightly hyperopic in all eyes (+0.12 to +1.50 D). All eyes showed a reduction in
      pre-existing higher order aberrations, ranging between 1% and 48%. Spherical
      aberration was reduced most (mean 38% reduction), coma was reduced by a mean 14%,
      and all other terms were reduced by a mean 17% compared to preoperative values.
      Subjectively, all patients noticed a reduction in their pre-existing visual
      symptoms and reported visual performance comparable to their fellow asymptomatic
      eye. Overall, the treatment was considered very satisfactory by patients in terms
      of visual quality gain. CONCLUSION: Wavefront-guided custom ablation with Alcon's
      LADARVision4000 was effective in reducing higher order aberrations and related
      visual symptoms in this preliminary small series. Longer follow-up on more eyes
      is necessary to assess the accuracy of the algorithm in the correction of
      defocus, which resulted in a slight overcorrection in this study.

PMID- 14640440
TI  - Exopeptidase degradation for the analysis of phosphorylation site in a mono
      phosphorylated peptide with matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - The utility of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) coupled with a peptide ladder sequencing method
      employing exopeptidase degradation for the analysis of phosphorylation site in a
      mono-phosphorylated peptide is investigated. MALDI-TOFMS analysis of time
      dependent exopeptidase digestion using carboxypeptidase W and aminopeptidase M of
      the mono-phosphorylated 33-48 fragment isolated from a beta-casein tryptic
      digestion mixture allowed for the sequencing analysis from both the C-terminus
      and N-terminus. Negative ion detection MALDI-TOFMS made it possible to clearly
      measure the peptide ladder of mono-phosphorylated peptide by the strong negative
      charge localized at the phosphoric acid group. Since exopeptidase activity was
      suppressed by the existence of a phosphorylated amino acid residue, the
      termination exopeptidase degradation therefore suggested the existence of a
      phosphorylated amino acid residue at that site. This peptide ladder sequencing
      method using exopeptidases was effective for the identification of the site of a
      phosphorylated amino acid residue by a simple MALDI-TOFMS analysis in the
      negative ion detection mode.

PMID- 14640441
TI  - A disposable voltammetric cell for determining the titratable acidity in vinegar.
AB  - A disposable voltammetric cell using three pencil leads as working, reference,
      and counter electrodes was developed for determining the titratable acidity, i.e.
      the acid content in vinegar. The materials of the pencil leads were graphite
      reinforcement carbons (GRCs). A voltammetric determination of acid was made by
      measuring the reduction prepeak current of 3,5-di-t-butyl-1,2-benzoquinone (DBBQ)
      due to the presence of acids in unbuffered solution. The potential stability of
      the pseudo-reference electrode of GRC was examined. The prepeak current was found
      to be proportional to the acetic acid concentration from 0.05 to 2.7 mM with a
      correlation coefficient of 0.999. The cell-to-cell reproducibility for 1 mM
      acetic acid was evaluated with ten individual disposable cells. The RSD of the
      prepeak current and the SD of the prepeak potential were 2.56% and 0.008,
      respectively. The titratable acidity in five vinegar samples was determined by
      voltammetry using disposable cells and compared with that of the titratable
      acidity determined by the conventional potentiometric titration method. We then
      observed the results by both methods, and found a correlation coefficient of
      0.972. As such, the voltammetry using disposable-cell required only one
      thousandth the volume of a vinegar sample for the titration method. The
      disposable cell was superior to the conventional electrochemical cell, in terms
      of facility, environment-friendly, and economy, and thus a sensor using the
      present cell would be useful for routine work in the quality control of vinegar.

PMID- 14640442
TI  - Application of polyaniline/sol-gel derived tetraethylorthosilicate films to an
      amperometric lactate biosensor.
AB  - The electrochemical entrapment of polyaniline (PANI) onto sol-gel derived
      tetraethylorthosilicate (TEOS) films deposited onto indium-tin-oxide (ITO) coated
      glass has been utilized for immobilization of lactate dehydrogenase (LDH). The
      performance of these sol-gel/PANI/LDH electrodes has been investigated as a
      function of the lactate concentration, applied potential, pH of the medium and
      interferents. The amperometric response of the electrodes under optimum
      conditions exhibited a linear relationship from 1 mM to 4 mM. An attempt has been
      made to extend the linearity up to 10 mM for lactate by coating an external layer
      of polyvinyl chloride (PVC) over the sol-gel/PANI/LDH electrodes with a
      correlation coefficient of 0.89. These sol-gel/PANI/LDH electrodes have a
      response time of about 60 s, a shelf life of about 8 weeks at 0-4 degrees C and
      have implications in a lactate biosensor.

PMID- 14640443
TI  - In vitro and short-term in vivo characteristics of a Kel-F thin film modified
      glucose sensor.
AB  - A new outer layer composition, consisting of polytetrafluoroethylene (PTFE), Kel
      F oil, and Nafion, is suggested to minimize the detrimental effect of dissolved
      oxygen and to extend the linear response range of a glucose oxidase(GOx)-based
      sensor using nonconducting polymer. The morphology of Kel-F/PTFE/Kel-F/Nafion
      polymeric laminate was followed during fabrication by SEM. When Kel-F film was
      formed on the PTFE outer layer, the linear response was extended to 21 mM, at a
      sensitivity of 2.8 +/- 0.8 nA/mM mm2. We demonstrate that a sensor without Kel
      F/PTFE/Kel-F/Nafion outer layer is relatively oxygen dependent, whereas by
      comparison a sensor with Kel-F/PTFE/Kel-F/Nafion outer layer is oxygen
      independent. The current of such a glucose sensor implanted in the subcutaneous
      tissue stabilized within 60 min, and the lag between blood glucose changes and
      sensor output was within 1 min. The in vivo characteristics of the glucose sensor
      described show great promise for one-point in vivo calibration.

PMID- 14640444
TI  - An organic solvent-free microwave-assisted extraction of some priority pollutants
      of phenols in lake sediments.
AB  - Alkaline water was used for the microwave-assisted extraction of some priority
      pollutants of phenols in sediments, i.e. phenol (Ph), 2-chlorophenol (2CP), 2,4
      dichlorophenol (2,4DCP), 4-chlorophenol (4CP), 4-dinitrophenol (4NP) and
      pentachlorophenol (PCP). This organic solvent-free extraction procedure was
      optimized by studying the parameters such as pH, volume of the alkaline water,
      extraction pressure and time. Under the optimized conditions, the recoveries of
      phenols were in the range of 80% to 110%. The extracts were then cleaned-up and
      concentrated by microcolumn solid phase extraction (SPE) and determined by gas
      chromatography-flame ionization detection system. The relative standard deviation
      of the overall-method for most phenol determinations was about 5.0% (n = 6). The
      proposed method, which needs little volume (1 mL) of ethanol for SPE, has been
      applied to determine these phenols in sediment samples, and the analytical
      results are in good agreement with those achieved by Soxhlet extraction.

PMID- 14640445
TI  - Solid-phase extraction of several phthalate esters from environmental water
      samples on a column packed with polytetrafluoroethylene turnings.
AB  - A method for the determination of several phthalate esters in water samples using
      solid-phase extraction coupled to high-performance liquid chromatography was
      developed. A polytetrafluoroethylene turnings packed column was used as a SPE
      adsorbent material. The analytes were sorbed on polytetrafluoroethylene turnings,
      from which they were eluted by a small amount of acetonitrile, followed by a RP
      HPLC-UV analysis. Detection limits (3sigma) of 4.7, 3.1, 3.6, 4.3, and 5.8 ng mL(
      1) for di-n-butyl-phthalate, di-cyclohexyl-phthalate, di-n-octyl-phthalate, di-n
      nonyl-phthalate and di-iso-decyl-phthalate, respectively, were achieved.
      Acceptable recovery results (92.1-127.5%) were obtained on five phthalate esters
      spiked samples.

PMID- 14640446
TI  - A low-cost light-scattering detector for the flow-injection nephelometric
      determination of sulfate.
AB  - A simple low-cost flow-through light-scattering detector was developed for
      determining the particle mass concentration in colloidal suspensions. Employing a
      laser pointer as a light source and a photodiode IC as a light sensor, the
      detector was shown to have good sensitivity, yet was small and battery operated.
      The detector was demonstrated to be effective for the flow-injection
      nephelometric determination of sulfate by precipitation as barium sulfate.

PMID- 14640447
TI  - Hexavalent chromium recovery by liquid-liquid extraction with tributylphosphate
      from acidic chloride media.
AB  - A method is introduced for recuperation of chromium(VI) in water samples by
      liquid-liquid extraction with tributylphosphate PO(C4H9O)3 (TBP) from acidic
      chloride media. The optimum conditions for quantitative extraction of Cr(VI) were
      evaluated by varying the experimental parameters, such as the shaking period, the
      pH of the aqueous phase, the hydrochloric acid concentration, the hydrogen and
      chloride ion concentrations, the extractant concentration and the ratio of
      aqueous-to-organic phase. The probable extracted species of hexavalent chromium
      in organic phase, deduced from log-log plots, were H2CrO4 in acid media in
      absence of chloride and HCrO3Cl in acidic chloride media. Chromium(VI) was found
      to be extracted with tributylphosphate from acidic chloride media according to
      the following reaction: HCrO4-(aq), + 2H+(aq) + Cl-(aq) + 2TBP(org) <==>
      [HCrO3Cl, 2TBP](org) + H2O(aq). Since the tributylphosphate (TBP) exhibited a
      high selectivity for chromium(VI), this method can be applicable to the
      extraction and the determination of chromium in both oxidation states [Cr(VI) and
      Cr(III)] in water samples.

PMID- 14640448
TI  - Determination of thallium(I) by flotation-spectrophotometric method using iodide
      and rhodamine B.
AB  - A method for the trace amount determination of Tl(I), via its preconcentration,
      is proposed. The method is based on the reaction of iodide, Tl(I) and Rhodamine B
      in a weakly acidic medium. In this process an ion-associated complex is formed,
      which is floated at the interface of aqueous-cyclohexane layers. Various amounts
      of Tl(I) by a subsequent separation and dissolution of the floated complex in
      methanol could be determined, spectrophotometrically. Beer's law was obeyed for
      the Tl(I) content in the range of (0.8-8.0) x 10(-7) mol l(-1) with a correlation
      coefficient of 0.9974. The conditional molar absorptivity was found to be 1.0 x
      10(6) l mol(-1) cm(-1) at 560 nm, which indicated the considerable sensitivity of
      the procedure. The detection limit (DL) was 4.7 x 10(-8) mol l(-1) and the RSD (n
      = 5) for 4 x 10(-7) mol l(-1) of Tl(I) was 3.34%. None of the alkaline cations
      was interfered, and the interference of many other metal ions was eliminated via
      ion-exchange separation using a cation-exchanger resin, Amberlite IR-120, before
      the flotation step. The reliability of the procedure was confirmed by determining
      the Tl(I) contents of synthetic laboratory waste water by both flotation
      spectrophotometry and graphite furnace atomic absorption spectrometry (GFAAS).
      The recovery was 92.3-95.4% for 1 x 10(-7) and 4 x 10(-7) mol l(-1),
      respectively. The precision and accuracy of the results were comparable via F and
      t tests at the 95% confidence level.

PMID- 14640449
TI  - Enantiomer separation of miconazole by capillary electrophoresis with dual
      cyclodextrin systems.
AB  - A cyclodextrin-modified micellar capillary electrophoretic method (MECC) was
      developed using mixtures of beta, cyclodextrins (beta-CD) and mono-3-O
      phenylcarbamoyl-beta-CD as chiral additives for the chiral separation of
      miconazole with the dual CDs systems. The enantiomers were resolved using a
      running buffer of 50 mmol/L borate pH 9.5 containing 15 mmol/L beta-CD and 15
      mmol/L mono-3-O-phenylcarbamoyl-beta-CD containing 50 mmol/L sodium dodecyl
      sulfate and 1 mol/L urea. A study of the respective influence of the beta-CD and
      the mono-3-O-phenylcarbamoyl-beta-CD concentration was performed to determine the
      optimal conditions with respect to the resolution. Good repeatability of the
      method was obtained.

PMID- 14640450
TI  - Second and first-derivative spectrophotometry for efficient simultaneous and
      individual determination of palladium and cobalt using 1-(2-pyridylazo)-2
      naphthol in sodium dodecylsulfate micellar media.
AB  - 1-(2-Pyridylazo)-2-naphthol (PAN) has been used for the simultaneous and
      individual determination of palladium and cobalt at trace levels. PAN complexes
      of palladium and cobalt at neutral pH form green-color neutral complexes, which
      are soluble in aqueous SDS micellar media. Under optimum conditions, calibration
      graphs for individual determinations by zero and first-derivative
      spectrophotometry, and also for simultaneous determinations by second-derivative
      spectrophotometry were obtained. A zero-crossing method using second-derivative
      spectrophotometry at 628 or 578 and 614 nm, respectively, for cobalt and
      palladium was used for simultaneous determinations. The method is able to
      determine the cobalt-to-palladium ratio, 5:1 to 1:10 (Wt/Wt), accurately. The
      accuracy and reproducibility of the determination method for various known
      amounts of cobalt and palladium in their binary mixtures were tested. The effects
      of diverse ions on the determination of cobalt and palladium to investigate the
      selectivity of the method were also studied. The recommended procedures were
      applied to a synthetic binary alloy, cobalt in vitamin B12 and B-complex
      ampoules, a Co2O3-Co3O4 laboratorial chemical mixture, some synthetic cobalt
      alloy samples, a Pd-charcoal catalyst, and some synthetic palladium alloys.

PMID- 14640451
TI  - Multielement determination of cadmium and lead in urine by simultaneous
      electrothermal atomic absorption spectrometry with an end-capped graphite tube.
AB  - A method for the multielement determination of cadmium and lead in urine is
      proposed by simultaneous electrothermal atomic absorption spectrometry (SIMAAS)
      with an end-capped transversely heated graphite atomizer (EC-THGA). The best
      conditions for cadmium and lead determination were obtained in the presence of
      NH4H2PO4 as a chemical modifier, using 500 degrees C and 1800 degrees C as the
      pyrolysis and atomization temperatures, respectively. Urine samples were diluted
      1 + 4 directly in autosampler cups with a mixture of 0.125% (w/v) Triton X-100 +
      2.5% (v/v) HNO3 + 0.31% (w/v) NH4H2PO4. The optimized heating program was carried
      out in 57 s, and the instrument calibration was done with aqueous reference
      solutions. The use of EC-THGA increased the sensitivity of cadmium and lead by
      14% and 25%, respectively. The detection limits (n = 20, 3delta) were 0.03 microg
      L(-1) (0.36 pg) for cadmium and 0.57 microg L(-1) (6.8 pg) for lead. The
      performance of EC-THGA was acceptable up to 500 heating cycles. The reliability
      of the entire procedure was checked with the analysis of a lyophilized urine
      certified reference material. The found concentrations were in agreement with the
      recommended values (95% confidence level).

PMID- 14640452
TI  - Determination of biguanide groups in polyhexamethylene biguanide hydrochloride by
      titrimetric methods.
AB  - The biguanide concentration of polyhexamethylene biguanide hydrochloride (PHMB
      HCl) was measured by non-aqueous titration with HClO4, argentometric titration,
      the Kjeldhal method, and colloidal titration. The summation value of non-aqueous
      titration and argentometric titration corresponded to two titrable nitrogens in
      five nitrogens per one unit of PHMB-HCl, and consisted with the result of the
      Kjeldhal method to the five nitrogens. The colloidal titration of PHMB-HCl at pH
      2.05 was equal to that with the two nitrogens. The relative standard deviations
      of non-aqueous titration, argentometric titration, the Kjeldhal method, and
      colloidal titration were 0.50% for 8 runs, 0.13% for 7 runs, 3.61% for 6 runs,
      and 0.69% for 6 runs, respectively.

PMID- 14640453
TI  - Test of significant differences with a priori probability in microarray
      experiments.
AB  - A traditional method for comparing two expression levels of genes in microarray
      experiments is the two-sample t-test. Because of the difficulty in using a large
      number of microarrays, an alternative method is required which can provide a
      reliable judgment of the comparison from a small number of replicates, even from
      a single pair of control and treatment. We present a method for detecting the
      changes in the gene expression levels under two different conditions in
      microarray experiments. Our method targets a single experiment for each
      condition, while retaining the statistical advantages of the t-test. The new
      proposals are: 1) standard deviation (SD) estimates of the expression levels
      which are an indicator for significant differences are given a priori as a
      function of the expression levels; 2) the limit of detection (LOD) for the
      expression levels is used to eliminate the majority of genes expressed at
      extremely low levels. The a priori SD estimates are obtained from six replicates
      under a fixed condition and are shown to be the approximate, but proper
      description of the expression uncertainty covering diverse conditions (e.g.,
      different samples (human and rat) and different DNA chips). The LOD is defined as
      three times blank SD according to the IUPAC recommendation. A cell line (HL60)
      which will undergo macrophage differentiation on treatment with 12-O
      tetradecanoylphorbol 13-acetate (TPA) is taken as an example. Our method is
      compared with the t-test for the data on duplicate TPA experiments and the former
      alone is evaluated with the data on a single TPA experiment. The errors from
      sample preparation and instrumental analysis are discussed.

PMID- 14640454
TI  - Enhanced peroxidase activity of hemoglobin in a DNA membrane and its application
      to an unmediated hydrogen peroxide biosensor.
AB  - Hemoglobin can exhibit not only a direct electron transfer reacting after being
      entrapped in a DNA membrane, but also a greatly enhanced peroxidase activity
      toward the reduction of hydrogen peroxide. Based on the direct electrochemical
      property and nice enzymatic activity of the protein in a DNA membrane, a
      reagentless hydrogen peroxide biosensor was prepared. The peak current related to
      hydrogen peroxide was linearly proportional to its concentration in the range of
      1.9 x 10(-6)-6.8 x 10(-4) mol L(-1). The detection limit was 1 x 10(-6) mol/L.

PMID- 14640455
TI  - Capillary electrophoresis of small anions in complex samples with a hollow fiber
      sampling inlet end.
AB  - A hollow fiber sampling inlet end of capillary electrophoresis (CE) for small
      ions in complex samples is described. A short piece of hollow fiber, which only
      permits small ions to pass through its wall, was directly connected to one end of
      a capillary. Small ions in complex samples were injected into the capillary
      through the hollow fiber by an electrokinetic method. The experimental results of
      CE for standard anion mixture solutions, river water, and milk samples show that
      the hollow fiber sampling inlet end is a simple and useful method for the CE of
      complex samples. Furthermore, it has been shown that the method can be used to
      study small anion changes during the milk storing process.

PMID- 14640456
TI  - Quantitative analysis of trace bulk oxygen in silicon wafers using an inert gas
      fusion method.
AB  - This paper describes a method for removing oxide film from the surface of silicon
      wafers using an inert gas fusion impulse furnace and precise determination of
      bulk oxygen within the wafer. A silicon wafer was cut to about 0.35 g (6 x 13 x 2
      mm) and dropped into a graphite crucible. The sample was then heated for 40 s at
      1300 degrees C. The wafer's oxide film was reduced by carbon and removed as
      carbon monoxide. The treated silicon sample was taken out of the graphite
      crucible and maintained again with the holder of the oxygen analyzer. The
      graphite crucible was then heated to 2100 degrees C. The treated silicon sample
      was dropped into the heated graphite crucible and the trace bulk oxygen in the
      wafer was measured using the inert gas fusion infrared absorption method. The
      relative standard deviations of the oxygen in silicon wafer samples with the
      removed surface oxide film were determined to be 0.8% for 9.8 x 10(17) atoms/cm3,
      and 2.7% for 13.0 x 10(17) atoms/cm3.

PMID- 14640457
TI  - A facile spectrophotometric method for cobalt determination using alpha
      benzilmonoxime in sodium dodecylsulfate micellar solutions.
AB  - Alpha-benzilmonoxime in sodium dodecylsulfate micellar media has been used for
      the spectrophotometric determination of cobalt at pH 9.0. The linear range of
      calibration is 0.05-1.50 microg cm(-3) of cobalt at 380 nm with molar
      absorptivity of 3.72 x 10(4) dm3 mol(-1) cm(-1), which is about 1.5-times greater
      than that of the alpha-benzilmonoxime extraction based method. The relative
      standard deviations, recoveries, detection limit and effects of diverse ions on
      the determination of cobalt were studied. These analytical results were
      satisfactory. The method was successfully applied to the determination of cobalt
      in the various samples.

PMID- 14640458
TI  - Canonical discriminant analysis of cadmium content levels in unpolished rice
      using a portable near-infrared spectrometer.
AB  - Near-infrared analysis (NIRA) was applied to discriminate and determine the
      cadmium content levels of unpolished rice using canonical discriminant analysis
      (CDA). The overall correct classification rate was 85.2% for 318 NIR spectra,
      repeated three times for 106 samples. After a further improvement through
      decreased misclassification rates, NIRA could be useful as a rapid,
      nondestructive and convenient analytical method for primary screening and
      detecting of cadmium-polluted rice.

PMID- 14640459
TI  - FTIR-ATR evaluation of organic contaminant cleaning methods for SiO2 surfaces.
AB  - The effectiveness of cleaning organic contaminants from silicon dioxide (SiO2)
      surfaces was studied by conducting highly sensitive measurements using Fourier
      Transform Infrared Attenuated Total reflectance (FTIR-ATR) with a Si prism as the
      waveguide. To serve as an example, the surface of the prism was oxidized to an
      order of a few nanometers. The oxidized Si surface film was allowed to stand in
      the atmosphere and then wet-cleaned in a repeated manner; subsequently its
      thickness was measured by ellipsometry. Although, various wet-cleaning methods
      were tested, they only showed values of 0.1-0.2 nm larger than, but not equal to,
      the original thickness immediately after oxidation. FTIR-ATR measurements of the
      spectral change after exposure to air revealed that organic species, such as C
      CH3 and -(CH2)n-, increased with time. Wet-cleaning the sample failed to remove
      the C-CH3 species, which indicates that they corresponded to the film thickness
      increment from the original.

PMID- 14640460
TI  - Estimation of metal impurities in high-purity nitric acids used for metal
      analysis by inductively coupled plasma-mass spectrometry.
AB  - A simple method to estimate the amounts of ultra-trace metal impurities in nitric
      acid reagents has been developed. The determination of sixty-four metals in
      nitric acid was accomplished by direct measurements of 0.1 M nitric acids
      accurately diluted with ultrapure water by ICP-MS. Though accurate metal
      concentration could not be obtained for all of the elements, we could effectively
      evaluate the nitric acid quality by comparing the ion counts of the samples,
      ultrapure water and standard metal solutions for a calibration prepared with
      Ultrapur nitric acid.

PMID- 14640461
TI  - Drug-eluting stents versus bare metal stents.

PMID- 14640462
TI  - New insights into the mechanisms of temporal variation in the incidence of acute
      coronary syndromes.
AB  - Over the last few years, patterns have emerged regarding the daily (circadian),
      weekly (circaseptan), and yearly (circannual) variation in the incidence of acute
      coronary syndromes (ACS). Peaks of incidence occur in the morning, on Mondays,
      and in winter. There is a difference in the pattern of incidence in different
      subgroups such as diabetics and smokers, which, along with the incidence
      alteration seen with aspirin and beta blockers, gives us some potential
      understanding of underlying mechanisms. Recent advances in the study of
      endothelial function, cytokine biology, and adhesion molecules have led to new
      insights into the way that natural fluctuations in these systems may affect ACS
      incidence. It is hoped that understanding these developments will lead to
      therapeutic advances in ACS prevention.

PMID- 14640463
TI  - Angiotensin II blockade: a therapeutic strategy with wide applications.
AB  - Evidence now exists suggesting a pathologic role for angiotensin II in patients
      with cardiovascular disease and those with risk factors. Clinical trials such as
      the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE),
      the Heart Outcomes Prevention Evaluation Study (HOPE), the African American Study
      of Kidney Disease and Hypertension (AASK), and the Reduction of Endpoints in
      NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study have clearly
      demonstrated that blood pressure reduction is important in hypertension and
      diabetes. If this can be accomplished with agents that block the renin
      angiotensin system, then additional clinical benefit will be achieved. Clinical
      data on angiotensin-converting enzyme inhibitors (ACEIs) are well established,
      while emerging data on the use of angiotensin II receptor blockers (ARBs)
      continue to grow. There is evidence supporting the concept of angiotensin II
      escape in the presence of ACEIs. The question that remains to be answered is
      whether a combination of both agents (ACEIs and ARBs) can improve clinical
      outcomes. Ongoing clinical trials will answer this question.

PMID- 14640464
TI  - Changes in the response of hibernated myocardium to inotropic stimulation after
      angioplasty: a Doppler myocardial imaging study.
AB  - BACKGROUND: Angioplasty of an infarct related artery (IRA) performed several
      weeks or months after myocardial infarction (MI) may improve myocardial function.
      HYPOTHESIS: We hypothesized that, as Doppler myocardial imaging (DMI) allows for
      the quantitative assessment of the systolic movement of myocardial segments, it
      may be a sensitive method for assessing changes in regional myocardial
      contraction and contractile reserve pre and post angioplasty of the IRA. METHODS:
      In all, 39 patients (30 men, mean age 53.4 +/- 8.3 years), 1 to 6 months after
      MI, who qualified for IRA angioplasty on the basis of myocardial viability in the
      infarcted zone as demonstrated by dobutamine stress echocardiography, were
      included in the study. Peak regional myocardial systolic velocities (S wave) of
      the infarcted segments were measured at rest and during low-dose dobutamine
      infusion (15 microg/kg/min) 1 day before angioplasty (Exam 1), 2 to 5 days (Exam
      2), and 30 days (Exam 3) after successful angioplasty. The long-axis movement of
      the mitral annulus and of the basal and medial segments of the posterior (20
      patients), anterior (17 patients), and lateral walls (2 patients) was evaluated.
      RESULTS: At rest, S-wave velocity of the infarcted segments increased between
      Exams 1 and 2, without further improvement between Exams 2 and 3 (4.9 +/- 1.2 vs.
      5.6 +/- 1.3 cm/s, p < 0.05 and 5.6 +/- 1.3 vs. 5.5 +/- 1.3 cm/s, NS,
      respectively). However, S-wave velocities measured during low-dose dobutamine
      infusion differed significantly both between Exams 1 and 2, and 2 and 3 (7.0 +/-
      1.5 vs. 7.8 +/- 1.8 cm/s; p < 0.01; 7.8 +/- 1.8 vs. 8.5 +/- 1.6 cm/s; p < 0.05).
      CONCLUSIONS: Resting contractility at an infarct zone demonstrated rapid initial
      improvement after angioplasty of the IRA with no further change, whereas
      contractile reserve improved not only immediately after angioplasty but also
      during the next month.

PMID- 14640465
TI  - Differential effects of simvastatin and atorvastatin on high-density lipoprotein
      cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic
      patient subgroups.
AB  - BACKGROUND: In addition to lowering plasma levels of low-density lipoprotein
      cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL
      C). HYPOTHESIS: Recent studies have shown that treatment with simvastatin results
      in larger increases in HDL-C than those seen with atorvastatin. The results of
      three clinical studies are analyzed, comparing the effects of simvastatin and
      atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in
      several subgroups of hypercholesterolemic patients. The three studies were all
      multicenter, randomized clinical trials that included simvastatin (20-80 mg) and
      atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were
      gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40
      mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160
      mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl). RESULTS: Both
      drugs produced similar increases in HDL-C levels at low doses; however, at higher
      drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with
      simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C
      remained consistently elevated across all doses of simvastatin, there appeared to
      be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A
      similar negative dose response pattern was also observed with apo A-I in
      atorvastatin-treated patients, suggesting a reduction in the number of
      circulating HDL particles at higher doses. Both drugs reduced LDL-C and
      triglycerides in a dose-dependent fashion, with atorvastatin showing slightly
      greater effects. The differential effects of atorvastatin and simvastatin on HDL
      C and apo A-I were observed for both the whole study cohorts and all subgroups
      examined; thus, no consistent treatment-by-subgroup interactions were observed.
      CONCLUSION: The data presented show that, across different hypercholesterolemic
      patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin
      at higher doses, with evidence of a negative dose response effect on HDL-C and
      apo A-I with atorvastatin, but not simvastatin.

PMID- 14640466
TI  - Insulin resistance and maximal oxygen uptake.
AB  - BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all
      correlate with insulin resistance, but the relative importance of each component
      is unknown. HYPOTHESIS: This study was undertaken to determine the relationship
      between insulin resistance, maximal oxygen uptake, and the presence of either
      diabetes or ischemic heart disease. METHODS: The study population comprised 33
      patients with and without diabetes and ischemic heart disease. Insulin resistance
      was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was
      measured during a bicycle exercise test. RESULTS: There was a strong correlation
      between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p =
      0.001), and maximal oxygen uptake was the only factor of importance for
      determining insulin sensitivity in a model, which also included the presence of
      diabetes and ischemic heart disease. CONCLUSION: Maximal oxygen uptake may be a
      more important determinant for insulin sensitivity than ischemic heart disease
      and type 2 diabetes.

PMID- 14640467
TI  - Cardiac rupture and tamponade as captured on ventriculography.

PMID- 14640468
TI  - Characteristics of patients with abnormal stress technetium Tc 99m sestamibi
      SPECT studies without significant coronary artery diameter stenoses.
AB  - BACKGROUND: Single-photon emission computed tomography (SPECT) sestamibi (MIBI)
      is an excellent tool for detection of coronary artery disease (CAD), preoperative
      risk assessment, and follow-up management after coronary revascularization. While
      the sensitivity of MIBI SPECT for detecting CAD has been reported to exceed 90%,
      the specificity ranges between 53-100%. HYPOTHESIS: The study was undertaken to
      assess characteristics of patients with abnormal stress technetium Tc99m
      sestamibi SPECT (MIBI) studies without significant coronary artery diameter
      stenoses (< 50%). METHODS: Between January 1999 and November 2000, 270
      consecutive patients were referred for coronary angiography due to reversible
      MIBI uptake defects during exercise. In 41 patients (15%; 39% women, mean age 59
      +/- 9 years), reversible MIBI uptake defects were assessed although coronary
      angiography showed no significant CAD. These patients were compared with age- and
      gender-matched patients with perfusion abnormalities (39% women, mean age 60 +/-
      9 years), due to significant CAD (coronary artery stenosis > 50%). RESULTS: There
      were no significant differences between the two groups regarding body mass index,
      left bundle-branch block (LBBB), or method of stress test (dipyridamole in
      patients with LBBB or physical inactivity [n = 11] and exercise in all the others
      [n = 30]). Left ventricular hypertrophy (44 vs. 23%, p = 0.05) and left anterior
      fascicular block (LAFB) (17 vs. 0%, p = 0.005) were more common in patients with
      perfusion abnormalities with no significant CAD, whereas ST-segment depression
      during exercise (17 vs. 37% p = 0.05) and angina during exercise (15 vs. 29%, p =
      0.02) were significantly less common than in patients with abnormal MIBI
      perfusion studies and angiographically significant CAD. Sestamibi uptake defects
      during exercise were significantly smaller in patients without significant CAD
      than in matched controls with significant CAD (p < 0.0004). CONCLUSION: Of 270
      consecutive patients, 41 (15%) referred to coronary angiography due to reversible
      MIBI uptake defects showed coronary artery stenoses < 50%. Twenty-six (10%) of
      these presented angiographically normal coronary arteries. The significantly
      higher proportion of left ventricular hypertrophy and LAFB in patients with
      reversible MIBI uptake defects without significant CAD suggest microvascular
      disease, angiographically underestimated CAD, and conduction abnormalities as
      underlying mechanisms.

PMID- 14640469
TI  - Practicability and limitations of enhanced external counterpulsation as an
      additional treatment for angina.
AB  - BACKGROUND: An increasing number of clinical studies indicates reduction of
      angina and myocardial ischemia by enhanced external counterpulsation (EECP)
      therapy. However, given the wide range of contraindications and the long duration
      of treatment, eligibility and practicality issues have not been addressed
      systematically. HYPOTHESIS: Of all candidates for EECP (patients with drug
      refractory angina without possibility of revascularization), the majority either
      have contraindications or have practical problems complying with the time demands
      that this therapy imposes. In the rest, EECP leads to satisfactory results.
      METHODS: During 18 months, every consecutive patient with angina despite medical
      and interventional therapy was evaluated for EECP at one center. Treated patients
      underwent a bicycle exercise test and perfusion imaging before and after the
      standard course of 35 h of EECP. In addition, patients were asked about frequency
      of angina and nitroglycerin usage before and after EECP, and all patients filled
      out a final questionnaire 1 year after the end of therapy. RESULTS: Overall, 48
      patients were considered candidates for EECP. Of these, 24 were excluded for
      medical reasons: poor ejection fraction (4), peripheral artery disease (4),
      anticoagulation (4), and atrial fibrillation (3). Eight further patients declined
      EECP for lack of time or accommodation. Another 3 of the 16 remaining patients
      dropped out because of side effects. In the 13 patients who finished the
      treatment course, weekly anginal episodes were reduced by 48% (p < 0.05), on
      demand nitroglycerin puffs were reduced by 51% (p < 0.05), work capacity was
      improved by 22% (p < 0.05), and the number of reversible perfusion defects in
      perfusion scans decreased nonsignificantly (-28%). However, 4 of 13 treated
      patients determined 1 year later that the detriment of loss of time exceeded the
      benefits of EECP. CONCLUSION: Similar to previous reports, our study confirms the
      reduction of angina and improvement of work capacity after EECP. However, using
      established contraindications, approximately two-thirds of patients considered to
      be candidates had to be excluded, and one-third of the treated patients regarded
      EECP therapy retrospectively as too time consuming.

PMID- 14640470
TI  - Additive value of low-dose dobutamine to technetium-99m sestamibi-gated single
      photon emission computed tomography for prediction of wall motion improvement in
      patients undergoing coronary artery bypass graft.
AB  - BACKGROUND: The two most useful methods for myocardial viability assessment are
      perfusion imaging and dobutamine echocardiography. HYPOTHESIS: The present study
      investigated the additive value of a new method, dobutamine technetium 99m
      (99mTc)-sestamibi-gated single-photon emission computed tomography (SPECT), which
      combines these two modalities, to the prediction of wall motion improvement after
      revascularization. METHODS: Fifty-five consecutive patients with ischemic
      cardiomyopathy, who were referred for viability evaluation, underwent resting and
      dobutamine (dose, 5-10 microkg/kg/min) gated SPECT with 99mTc-sestamibi. Of these
      patients, 36 underwent coronary artery bypass graft (CABG) within 1 month of the
      study and 32 had repeat resting gated SPECT within 1 year. Global and regional
      wall motion, wall thickness, and perfusion were simultaneously analyzed at rest
      and after dobutamine using the 20-segment model; the sestamibi uptake and wall
      motion response to dobutamine of each segment were rated quantitatively. Based on
      these findings, the segments were categorized as normal, viable, or nonviable.
      The predictive values for wall motion improvement were assessed by perfusion,
      using cutoffs of 50 and 60% of sestamibi uptake, and thereafter by the addition
      of dobutamine response in the segments that were rated nonviable. RESULTS: Of the
      1,080 myocardial segments studied, 906 (84%) had abnormal wall motion and were
      analyzed for viability. Concordance between perfusion and wall motion response to
      dobutamine was 60% with the 50% cutoff of sestamibi uptake, and increased to 65%
      with the 60% sestamibi cutoff (p < 0.04). The respective predictive values of
      wall motion improvement using the 50 and 60% cutoff points were as follows:
      sensitivity 93 and 70%, respectively, (p < 0.01); specificity 59 and 86% (p <
      0.001), respectively; accuracy 77% for both. The addition of the wall motion
      response to dobutamine to the assessment of the nonviable segments by perfusion
      (60% cutoff) increased the sensitivity from 70 to 85% (p = 0.001) and the
      negative predictive value from 70 to 81% (p = 0.009); the positive predictive
      value remained high (86 vs. 82%). No additive value of wall motion response to
      dobutamine was demonstrated for nonviable segments by perfusion with a 50%
      cutoff. CONCLUSION: Dobutamine sestamibi-gated SPECT is a feasible method for the
      analysis of myocardial perfusion, function, and contractile reserve of individual
      myocardial segments in patients with ischemic cardiomyopathy. Viability
      assessment based on a threshold of 60% uptake of sestamibi, with the addition of
      the wall motion response to dobutamine in the nonviable segments, seems to yield
      better predictive values for wall motion improvement after CABG.

PMID- 14640471
TI  - Autopsy findings in siblings with hypertrophic cardiomyopathy caused by Arg92Trp
      mutation in the cardiac troponin T gene showing dilated cardiomyopathy-like
      features.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes
      that encode sarcomeric proteins. Although some patients with HCM have shown
      dilated cardiomyopathy (DCM)-like features, the relationship between genotype and
      histologic findings is not well known. HYPOTHESIS: Family members with the same
      gene mutation may show the same histopathologic changes and clinical
      manifestations. METHODS: Siblings with HCM caused by an Arg92Trp mutation in the
      cardiac troponin T gene, showing DCM-like features, were examined. RESULTS: The
      patients were a 69-year-old woman and her 57-year-old brother who both died from
      congestive heart failure. Their autopsies revealed the same histopathologic
      findings in the heart. The anterior walls and interventricular septa of their
      hearts were replaced with extensive fibrosis and showed thinning. Myocyte
      hypertrophy, disarray, and thickened medial walls of the intramural coronary
      arteries were found. On electron microscopy, the number of mitochondria was seen
      to be increased and they formed many clusters. CONCLUSIONS: Patients with HCM
      caused by an Arg92Trp mutation in the cardiac troponin T gene may have the same
      histopathologic findings, which may result in DCM-like features.

PMID- 14640472
TI  - Focal hypertrophic cardiomyopathy simulating a mass.

PMID- 14640473
TI  - A new terminology for describing left and right ventricular conduction
      abnormalities.
AB  - The words we use to describe a medical condition should match our knowledge of
      it. Unfortunately, at times, the words we used long ago persist after new
      knowledge of the subject has become apparent; so it is with left and right
      ventricular conduction system abnormalities. The words left or right bundle
      branch block no longer reflect our knowledge of the condition. Accordingly, this
      essay describes a new terminology that more accurately describes the numerous
      abnormalities that compose left and right ventricular conduction system block as
      well as their numerous subsets. A brief account of the cardiac conditions
      associated with the conduction defects is also presented.

PMID- 14640474
TI  - Timothy J. Regan.

PMID- 14640475
TI  - Unusual evolution of mitral flail leaflet.

PMID- 14640476
TI  - Assessment of some clinical and laboratory variables for early diagnosis of
      cumulative copper poisoning in sheep.
AB  - Sixteen male Suffolk lambs fed a 8 ppm Cu basal diet were randomly assigned to 2
      groups: 12 copper-loaded (CL) and 4 controls (C). The CL sheep were drenched
      initially with 3 mg Cu/kg bw daily for a week. Every week an additional dose of 3
      mg Cu/kg bw was included in the drench until signs of copper poisoning appeared;
      the control sheep were drenched with saline solution. The onset of copper
      poisoning occurred between 42 and 55 d. Food intake and body weight were recorded
      daily. Blood samples were collected weekly to measure the activity of the liver
      enzymes gamma-glutamyltransferase (gammaGT), aspartate aminotransferase (AST),
      sorbitoll dehydrogenase (SDH) and acid phosphatase (AF). The following changes
      were significantly recorded in the CL sheep in the weeks or days previous to the
      hemolytic crisis: higher levels of gammaGT were found on the -28th d increasing
      slowly but continuously until the hemolytic crisis; SDH fluctuated during the
      period presenting higher levels on the -28th, -14th and -7th d; AST and AF
      activities increased from the -14th and -7th d respectively; sharp decreases in
      the activities of SDH and AF at the hemolytic crisis; lower feed intake and body
      weight gain from the -7th d; and sheep ceased eating concentrates from the -9th d
      and became anoretic the day before the hemolytic crisis. Plasma copper
      concentration increased only the day before the hemolytic crisis. There were no
      changes in respiratory and heart rates, rectal temperature or rumen movements
      throughout the pre-hemolytic phase. The higher the amount of cumulative copper
      drenched, the higher was the gammaGT and AST activities. It was concluded that
      gammaGT followed by AST are the best enzymes to assess copper-load in sheep
      during the pre-hemolytic phase. Sheep fed copper-rich diets with high plasma
      activity of these enzymes, decreased feed consumption and subtle loss of body
      weight are most likely to present with a hemolytic crisis in a few days.

PMID- 14640477
TI  - Selenium toxicity in sheep grazing reclaimed phosphate mining sites.
AB  - Phosphate mining operations in southeastern Idaho have exposed selenium (Se) that
      was originally sequestered in the subsurface. Sheep grazing in these areas have
      died as a result of high Se concentrations in forage and water. This study was
      designed to monitor the health status of sheep grazing in a natural environment
      with known elevated levels of Se. A total of 72 Columbia x Suffolk sheep were
      divided into 3 treatment groups that included control (Con), low selenium (LoSe)
      and high selenium (HiSe). The baseline phase of the study was conducted in an
      area with normal background Se levels in forage and water, and was grazed for 3 w
      by all sheep groups. The sheep then were moved onto reclaimed mine areas to begin
      the 4-w exposure phase. This was followed by a 2-w depuration phase where sheep
      again received normal Se levels in forage and water. The Con group was held on
      areas with normal Se levels of forage (< 0.32 ppm Se dw) and water (< 1.70 ppb
      Se). The LoSe group was held in an area of elevated forage Se (< 13.0 ppm Se dw)
      and normal Se levels in their water (< 1.70 ppb Se) during the exposure phase.
      The HiSe group was held on mining areas with elevated Se forage (< 49.0 ppm Se
      dw) and drinking water (340 to 415 ppb Se). Whole blood and serum levels in the
      HiSe group peaked at 1.32 and 0.99 ppm mean Se, respectively. The LoSe group had
      mean whole blood and serum Se levels of 0.75 ppm on day 42 and 0.32 ppm on day 35
      respectively. The Con group maintained low Se levels in both whole blood and
      serum that ranged from 0.05 to 0.14 ppm and 0.06 to 0.13 ppm respectively. The Se
      exposure in the HiSe group was estimated 0.26 mg Se/kg body weight/d. One sheep
      in the HiSe group died and was diagnosed with Se toxicosis based on clinical
      signs, histopathology and tissue Se levels. Se in liver (3.90 ppm), kidney (1.90
      ppm) and skeletal muscle (0.70 ppm) were indicative of high to toxic Se exposure.
      Two other sheep necropsied after the exposure phase also had Se concentrations in
      liver, kidney and skeletal muscle representative of high or toxic Se exposure
      (5.50, 3.50 and 1.10 ppm Se), but these sheep had no gross or histopathological
      signs of illness. More research is needed on the toxicology of Se in sheep
      grazing natural settings.

PMID- 14640478
TI  - Toxic effects of prenatal Ipomoea carnea administration to rats.
AB  - Chronic exposure of livestock to Ipomoea carnea, a toxic plant, promotes
      toxicosis characterized by lysosomal vacuolization of different organs, and is
      clinically manifested by CNS signs, abnormal endocrine and gastrointestinal
      functions, alteration of the immune system, and abnormal embryogenesis. The
      present study evaluated the effects of different doses of the plant extract on
      pregnant rats and their offspring after oral administration to the dams from day
      6 to day 20 of gestation. Histopathology of thyroid, pancreas, liver and kidneys
      of dams on gestational day 21 showed characteristic vacuolization promoted by I.
      carnea toxicosis in these organs; the same was observed in the organs of 7-d-old
      pups. On the other hand, no alteration was found in these same organs of dams the
      7th d after parturition. Although the lesions were reversed in the dams, the same
      did not occur in their pups. I. carnea administration also promoted decreased
      body weight, thymus atrophy and spleen enlargement in pups. The toxic principle
      of I. carnea (swainsonine) seems to pass through the placenta.

PMID- 14640479
TI  - Death by quinine.
AB  - We report a case of a man with a 9.75 g ingestion of quinine. The patient
      presented with recurrent pulseless wide complex tachycardia for which he received
      sodium bicarbonate, defibrillation and overdrive mechanical pacing. Despite
      treatment, the patient died. Quinine is still available for the treatment of leg
      cramps and drug-resistant malaria. In overdose, quinine affects multiple organ
      systems, including vision, hearing, the cardiovascular, and renal systems. We
      review the current approach to quinine intoxication.

PMID- 14640480
TI  - Sea-urchin envenomation.
AB  - Sea-urchin stings may produce injurious and venomous wounds. Although numerous
      writers refer to the danger of pedicellarial stings, there is little worth-while
      clinical data. We report a case of sea-urchin injury with severe local reaction
      and acute hepatitis. A 47-y-o Taiwanese woman accidentally stepped on a sea
      urchin while scuba diving on a beach in Palau Islands. The puncture wounds were
      numerous and she felt faintness, and immediate and intense pain. Initial
      management included partial spine removal, betadine immersion, intravenous fluid
      and analgesics. She developed fever, chills, nausea, and persistent serous
      discharge and tenderness from the sites of stings in the following days. She was
      admitted due to right foot cellulitis, sea-urchin injuries of both soles and
      suspected toxic hepatitis on the 7th day after envenomation. Serum alanine
      transaminase was 810 U/L and aspartate transaminase 320 U/L; she received i.v.
      antibiotics and wound debridement for removal of residual stings. She recovered
      gradually and was discharged 2 w later. Travel related marine animal injury has
      an increasing tendency throughout the world. This case had the unusual
      presentation of severe local reaction and hepatitis; immediate and more
      aggressive spine removal might have lessened the degree of injury.

PMID- 14640481
TI  - Accidental clozapine intoxication in a ten-year-old child.
AB  - Clozapine is a tricyclic dibenzodiazepine derivative used commonly in the
      treatment of schizophrenia. Severe side effects of overdose have been described
      in children. This report describes the unintentional ingestion of clozapine by a
      10-y-o girl, presenting dramatic changes of mental status and progressive
      alteration of consciousness with a Glasgow Coma Scale drop from 12 to 7. Urine
      analysis revealed 500 microg clozapine/L 24 h after ingestion. Full resolution of
      symptoms occurred after approximately 55 h with no sequels or alterations at
      follow-up. Awareness must be taken when administering atypical antipsychotics
      such as clozapine to children because of the severe intoxication effects cases
      reported.

PMID- 14640482
TI  - Overingestion of methionine tablets by a dog.
AB  - Methionine tablets are used as urinary acidifiers for pets and to decrease damage
      from dog urine to lawns. A 39-kg Labrador Retriever ingested approximately 350
      tablets containing 150 mg methionine/tablet and was presented after repeated
      episodes of vomiting. The only abnormality was posterior ataxia suggestive of
      spinal cord injury. The animal was treated with i.v. fluids, steroids and
      gastrointestinal protectants. Approximately 4.5 h after entering the clinic the
      dog had a single seizure episode lasting 2-3 min which was treated with
      phenobarbital. Serum ammonia at that time was normal (0.19 mg/dL). The animal did
      not show further CNS abnormalities and awoke apparently normal. A musty odor to
      the breath was noticed through the course of the day, possibly due to volatile
      mercaptans produced from methionine metabolism. The animal made an uneventful
      recovery and was discharged the next day.

PMID- 14640483
TI  - Dermal absorption of a liquid diphacinone rodenticide causing coagulaopathy.
AB  - Rare cases of coagulaopathies from dermal absorption of hydroxycoumarin
      derivatives have been reported. We report the first case of dermal absorption of
      an indandione derivative rodenticide causing severe coagulopathy. An 18-y-o male
      worker at a pest exterminating company spilled a concentrated liquid preparation
      of 0.106% diphacinone in his boot. He did not remove the boot or wash the area
      for 6 to 8 h. Seven days later he presented to the emergency department with
      flank pain, hematuria and epistaxis. Laboratory values were PT > 40 sec, PTT >
      90, Hb 16.2, and platelets 273. Urinalysis reported gross hematuria with RBCs too
      numerous to count. Prolonged bleeding was noted at i.v. puncture sites. Initial
      therapy included i.m. injection of vitamin K and nasal packing. The patient's
      religious beliefs precluded the use of blood products. The patient was admitted
      for observation until PT was controlled. He was discharged on high dose vitamin K
      p.o. dose titrated to the international normalized ratio measured every 48 h.
      After 2 w, a dose of 100 mg vitamin K/d was set and the patient was followed as
      an outpatient for 3 mo. Vitamin K therapy was tapered and discontinued 60 d post
      exposure with no further elevation in PT. Diphacinone was detected in a serum
      sample drawn 60 d post-exposure using gradient and isocratic HPLC methods with
      fluorescence and UV detection. Factors increasing the dermal absorption of the
      diphacinone were: prolonged skin contact in a confined area and exposure to a
      concentrated solution.

PMID- 14640484
TI  - Amphetamine poisoning in a dog: case report, literature review and veterinary
      medical perspectives.
AB  - Amphetamine abuse in human beings has increased, resulting in many reports of
      toxicity and death. In the US over 4 million people have abused amphetamines at
      least once, thus small animals are exposed to increased accidental poisoning
      risk. This report describes an acute amphetamine poisoning in a dog due to
      ingestion of 15 mg/kg fenproporex, leading to typical signs of catecholamines
      release and effects in different organ systems. Similar clinical and laboratory
      findings observed in human beings are reviewed and physiopathogenic mechanisms
      discussed, as well as the therapeutic approaches available in veterinary
      medicine.

PMID- 14640485
TI  - Unintentional toxicity due to endosulfan: a case report of two patients and
      characteristics of endosulfan toxicity.
AB  - Unrestricted use of endosulfan, a cyclic chlorinated hydrocarbon insecticide,
      results in many intentional and unintentional toxicities in Turkey. Due to its
      chemical stability in the environment, toxicity may be seen even if exposure
      happens 6-mo after the endosulfan has been sprayed. We discuss a case of 2
      patients with unintentional exposure to endosulfan after eating contaminated
      foods, one of which presented with neurological manifestations and required
      mechanical ventilation, the other having only mild symptoms. Because of the
      toxicity to humans and threats for nature, use of endosulfan should be restricted
      or banned.

PMID- 14640486
TI  - 2,4-D (chlorophenoxy) herbicide poisoning.
AB  - 2,4-D poisoning is uncommon. We report 3 cases of acute intoxications with this
      compound, presenting clinical features, mechanisms of toxicity and management.

PMID- 14640487
TI  - Acute endosulfan poisoning in cattle.
AB  - Endosulfan poisoning was observed in cattle where the owner applied the
      insecticide topically as ectoparasitic control. Two of 11 cattle died in 2 d with
      rapid and difficult breathing, foamy exudates in the mouth, tremors, exophthalmos
      and coma. At necropsy, hemorrhages were on the serosal membranes of the visceral
      organs and lungs, and there was severe edema and emphysema in the lungs. The
      levels of endosulfan in the liver, kidney, lungs and muscle were 13.1, 4.0, 1.6
      and 0.8 ppm, respectively.

PMID- 14640488
TI  - Initial impact of toll-free access on poison center call volume.
AB  - Prior to the implementation of the nationwide toll-free telephone number, most
      poison centers already provided toll-free service; therefore, the impact of toll
      free access to a poison center on call volume is difficult to assess in the
      majority of poison centers. This analysis examined the effect that the new
      nationwide toll-free telephone number had on total call volume (exposures and
      information calls) in a poison center without previous toll-free access and
      serving a large urban and rural population. All calls received by a Regional
      Poison Information Center (RPIC) over a consecutive 27-mo period (2000, 2001, Jan
      Jun 2002) were analyzed. April 2001 was the first full month of toll-free
      service. Data from January-March and January-June for 2000, 2001 and 2002 served
      as 3 and 6-mo benchmark and study periods. The 3 and 6-mo periods for each of the
      3 years were used to conduct comparative trend analysis. Over 1.1 million pieces
      of literature and sheets of stickers that contained the toll-free number were
      distributed throughout the region over the study period. Use of the toll-free
      number increased from 590 calls in July 2001 to 2,157 in June 2002. Total call
      volume increased by 11.2%. Trend analysis revealed a 9.9% increase in exposure
      volume when comparing 2001 and 2002 data. There was a significant increase in
      utilization of the toll-free number for information purposes from people residing
      in rural counties. Toll-free access to the RPIC increased the volume of
      information calls dramatically. Initial trend analysis indicated that the
      availability of toll-free access has reversed the erosion of exposure-related
      calls.

PMID- 14640489
TI  - The epidemiology of pepper spray exposures reported in Texas in 1998-2002.
AB  - Pepper spray is used as an incapacitant agent. Although now available for general
      use in the US, the health consequences of pepper spray exposures are poorly
      understood. This study used data from human exposure calls to poison centers in
      Texas to investigate the epidemiology of pepper spray exposures. During 1998-2002
      there were 1,531 human exposures to pepper spray identified by the Texas poison
      centers. Pepper spray reports declined during the 5-y period of the study. The
      majority of exposures were unintentional (84%), occurred at home (68%), involved
      males (56%), and comprised children and adolescents (64%). Risk factors for
      pepper spray exposure varied by patient age. Although 85% of the pepper spray
      exposures were managed outside of health care facilities, 97% of exposures
      involved at least minimal notable clinical effects. Given the level of detectable
      clinical effects of this intervention and the widespread availability of these
      agents, there is a need for better education of the public regarding the proper
      use of pepper spray and the effects of its use.

PMID- 14640490
TI  - The knowledge and attitude of rural children about poisonings.
AB  - Childhood poisonings are an important problem. The goal of the study was to
      implement and evaluate poisoning prevention training for primary school students.
      The study was carried out in 3 rural schools Kemalpasa, Izmir, Turkey. Fourth and
      5th grade students completed age appropriate questionnaires pre- and post
      education. There were significant differences in mean scores of the knowledge
      responses given pre- and post-test (p<0.05). with more questions answered
      correctly post-education.

PMID- 14640491
TI  - Acute methanol poisonings reported to the Drug and Poison Information Center in
      Izmir, Turkey.
AB  - The demographics, sources and outcomes of methanol poisoning have not been
      described in Turkey. Our study identified the profile of acute methanol exposures
      reported to Drug and Poison Information Center (DPIC) in Izmir, Turkey, from 1993
      to 2002. Data analysis included patient demographics, sources of methanol, reason
      for the exposure, clinical effects and outcomes of methanol poisoning. The DPIC
      recorded 30,485 calls concerning poisoning; 996 (3.3%) alcohol poisonings were
      recorded and 113 (11.3%) of them were methanol poisonings. There were 91 (80.5%)
      males and 22 (19.5%) females with a mean age of 34.7+/-1.3 y (range 19-65) and
      4.8+/-0.9 y (range 1-18) in adults and children, respectively. The sources of
      methanol were eu de cologne (72.6%), spirits (10.6%) and antifreeze (2.7%).
      Accidental poisoning occurred in all children between 0 and 12 y old, abuse
      (55.7%) and intentional poisoning (27.3%) were predominant in adults. Clinical
      signs in all cases were central nervous system symptoms (45.1%), metabolic
      acidosis (23.0%), visual symptoms (21.2%) and gastrointestinal symptoms (10.6%).
      Sixteen patients (14.1%) died, 63 (55.8%) had complete recovery and 1 (0.9%) had
      irreversible visual problems. Most patients with methanol poisoning may die or
      present serious morbidity without appropriate treatment in a health care
      facility. Methanol for producing cheap "eu de colognes" in Turkey is the
      principal reason for severe poisoning and deaths. Public education about colognes
      and legislative control of cologne production are important in preventing
      methanol poisoning.

PMID- 14640492
TI  - An ultrastructural study of the brain in fatal Plasmodium falciparum malaria.
AB  - Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum
      malaria. We present quantitative electron microscopic findings of the
      neuropathologic features in a prospective clinicopathologic study of 65 patients
      who died of severe malaria in Thailand and Vietnam. Sequestration of parasitized
      red blood cells (PRBCs) in cerebral microvessels was significantly higher in the
      brains of patients with CM compared with those with non-cerebral malaria (NCM) in
      all parts of the brain (cerebrum, cerebellum, and medulla oblongata). There was a
      hierarchy of sequestration with more in the cerebrum and cerebellum than the
      brain stem. When cerebral sequestration was compared with the peripheral
      parasitemia pre mortem, there were 26.6 times more PRBCs in the brain
      microvasculature than in the peripheral blood. The sequestration index was
      significantly higher in CM patients (median = 50.7) than in NCM patients (median
      = 6.9) (P = 0.042). The degree of sequestration of P. falciparum-infected
      erythrocytes in cerebral microvessels is quantitatively associated with pre
      mortem coma.

PMID- 14640493
TI  - Robust in vitro replication of Plasmodium falciparum in glycosyl
      phosphatidylinositol-anchored membrane glycoprotein-deficient red blood cells.
AB  - Red blood cells (RBCs) infected with Plasmodium falciparum are protected from
      complement-mediated lysis by surface membrane glycosyl-phosphatidylinositol (GPI)
      anchored proteins, which include decay accelerating factor (DAF or CD55) and
      CD59. To determine if P. falciparum avoids or replicates less efficiently in GPI
      protein-deficient cells at a higher risk for complement-mediated lysis, we
      compared P. falciparum infectivity among control RBCs with those from subjects
      with paroxysmal nocturnal hemoglobinuria (PNH), a condition in which RBCs express
      variable levels of DAF (negative and positive) and CD59 (negative [-],
      intermediate [I], and high [H]). Co-cultures of 19 matched samples of control and
      PNH RBCs were infected with P. falciparum to directly compare parasitic invasion.
      Each PNH RBC sample was then assessed for P. falciparum infectivity across the
      spectrum of GPI protein deficiency. Identification methods included biotin
      streptavidin for RBC populations, fluorescein isothiocyanate-labeled antibodies
      to DAF and CD59, hydroethidine for parasite DNA, and flow cytometry. The mean +/-
      SD parasitemias in co-cultured PNH and control RBCs were 24.7 +/- 6.9% versus
      21.0 +/- 5.9% (P = 0.12). For individual PNH samples, parasitemias were
      significantly higher in DAF (-) cells versus DAF (+) cells (25.0 +/- 8.9% versus
      19.1 +/- 8.7%; P < 0.001) and in CD59 (-) cells versus I/H cells (22.5 +/- 6.4%
      versus 17.6 +/- 4.2%; P < 0.0003). Across the CD59 spectrum, mean parasitemias
      were highest in CD59 (-) cells (24.5 +/- 6.4%), followed by CD59-H cells (19.5 +/
      5.4%), and CD59-I cells (16.4 +/- 4.8%). Expression of DAF in 12 (63%) of 19
      infected PNH samples was reduced. Thus, P. falciparum does not selectively avoid
      RBCs with fewer GPI proteins and parasite replication in PNH cells is at least as
      robust as in normal RBCs.

PMID- 14640494
TI  - Antipyretic, parasitologic, and immunologic effects of combining
      sulfadoxine/pyrimethamine with chloroquine or paracetamol for treating
      uncomplicated Plasmodium falciparum malaria.
AB  - Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub
      Saharan Africa because of chloroquine resistance. However, chloroquine may have a
      beneficial antipyretic effect. We therefore compared the combination of SP plus
      chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the
      treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian
      children (1-4 years old) in a randomized trial. Outcome variables were axillary
      temperatures every six hours, daily parasitemias, and serum levels of IgG
      antibodies to P. falciparum. Lower mean temperatures (6-48 hours) were achieved
      with SP plus chloroquine or paracetamol than with SP alone (P < 0.001) or
      chloroquine alone (P < 0.05). All three SP-treated groups showed high and similar
      parasite reduction (0-48 hours), whereas treatment with chloroquine alone was
      much less effective. Levels of IgG antibodies to P. falciparum increased
      significantly (P < 0.001) and similarly in the four treatment groups between days
      0, 2, and 3. Thus, the addition of chloroquine or paracetamol to SP improved the
      clinical outcome, but did not affect the parasitologic response or antibody
      production.

PMID- 14640495
TI  - Dependence of malaria detection and species diagnosis by microscopy on parasite
      density.
AB  - Giemsa-stained blood smears from each of 2,190 patients from Thai government
      operated clinics on the Thailand-Myanmar border were independently examined by
      the on-duty microscopists at the clinics and by 2-3 research microscopists, each
      blinded to the clinics' and each other's reports. Using a strictly defined
      protocol, a consensus reference-standard blood smear interpretation for each
      sample was produced by the research microscopists. This result was compared with
      the clinic's diagnostic interpretation for the corresponding sample with respect
      to detection of parasitemia and diagnosis of infecting species. Reference
      standard results reported parasitemia in 13.2% of the samples reported negative
      by the clinic. Reference-standard results were negative in 24.3% of the samples
      reported parasite-positive by the clinic. For samples in which both the reference
      standard result and the clinic result reported parasitemia, species
      identification differed for 13.7% of the samples. The likelihood of parasite
      detection and correct diagnosis at the clinic varied in accordance with the
      reference-standard estimates of parasite density.

PMID- 14640496
TI  - Identification of a polymorphic Plasmodium vivax microsatellite marker.
AB  - Microsatellite markers derived from simple sequence repeats have been useful in
      studying a number of human pathogens, including the human malaria parasite
      Plasmodium falciparum. Genetic markers for P. vivax would likewise help elucidate
      the genetics and population characteristics of this other important human malaria
      parasite. We have identified a locus in a P. vivax telomeric clone that contains
      simple sequence repeats. Primers were designed to amplify this region using a two
      step semi-nested polymerase chain reaction protocol. The primers did not amplify
      template obtained from non-infected individuals, nor DNA from primates infected
      with the other human malaria parasites (P. ovale, P. malariae, or P. falciparum).
      The marker was polymorphic in P. vivax-infected field isolates obtained from
      Papua New Guinea, Indonesia and Guyana. This microsatellite marker may be useful
      in genetic and epidemiologic studies of P. vivax malaria.

PMID- 14640497
TI  - Seroprevalence and risk factors for Trypanosoma cruzi infection in the Amazon
      region of Ecuador.
AB  - Trypanosoma cruzi infection in the Ecuadorian Amazon region has recently been
      reported. A seroepidemiologic survey conducted in four provinces in this region
      indicates a seroprevalence rate of 2.4% among the 6,866 samples collected in 162
      communities. Among children < OR = 10 years of age, 1.2% were seropositive. Risk
      factors for T. cruzi seropositivity were having been born and remaining in the
      Ecuadorian Amazon provinces, age, living in a house with a thatch roof and open
      or mixed wall construction, recognizing the vector insects, and reporting being
      bitten by a triatomine bug. These data suggest active transmission of Chagas'
      disease in the Ecuadorian Amazon region is associated with poor housing
      conditions, and highlight the need for further studies aimed at understanding the
      biology of the insect vectors, reservoir species, and the clinical impact of T.
      cruzi infection as the basis for future educational and control programs in this
      region.

PMID- 14640498
TI  - Mitochondrial cytochrome b variation in populations of the visceral leishmaniasis
      vector Lutzomyia longipalpis across eastern Brazil.
AB  - A population analysis of peridomestic, light-trapped, field specimens of the
      phlebotomine sand fly Lutzomyia longipalpis was targeted to six locations
      representing a geographic transect across eastern Brazil. Mitochondrial
      cytochrome b gene sequences established the pattern of genetic variation among
      the populations. Alignment of a 261-basepair region at the 3' end of cytochrome b
      identified 30 haplotypes and 21 segregating sites from 78 sand flies. Pairwise
      comparisons indicated statistically significant population structuring between
      northern and southern populations, as well as structuring among the southern
      populations. Prominent spatial clustering was evident for two of the populations
      in a minimum spanning network of the haplotypes, but sequence divergence was not
      sufficient to indicate cryptic species.

PMID- 14640499
TI  - Peridomestic risk factors for canine leishmaniasis in urban dwellings: new
      findings from a prospective study in Brazil.
AB  - Despite the wealth of information on the prevalence and correlates of canine
      Leishmania infection (CLI), data on its incidence are still sparse, and little is
      known regarding risk factors for CLI. We studied a cohort of dogs in an urban
      area in Brazil to determine whether incidence varied with age, breed, and
      environmental characteristics. The mean follow-up was 1.5 years, and the crude
      incidence rate was 11.8 cases/100 dog-years (95% confidence interval [CI] = 8.6
      15.6). In the multivariate analysis, short fur was the strongest predictor of CLI
      (relative risk [RR] = 9.4). In addition, our data indicate that raising pigs (RR
      = 4.1), chickens (RR = 3.3), or other livestock (RR = 2.6) significantly
      increased the risk of CLI. Thus, suggesting control measures directed towards
      modifying the environmental factors favoring contact between vectors, reservoirs,
      and susceptible humans, such as proximity to pigpens or hen houses. Furthermore,
      conventional control programs of insecticidal spraying of human dwellings should
      also apply insecticide in and around animal sheds.

PMID- 14640500
TI  - Epidemiologic and clinical characteristics of acute diarrhea with emphasis on
      Entamoeba histolytica infections in preschool children in an urban slum of Dhaka,
      Bangladesh.
AB  - The epidemiology, clinical features, nutritional status, and causative agents of
      diarrhea were studied in 289 Bangladeshi children (147 boys and 142 girls) 2-5
      years old. The use of improved diagnostic tests for amebiasis enabled for the
      first time analysis of the contribution of Entamoeba histolytica to total
      diarrheal illness in this community setting. The average incidence rate of
      diarrhea was 1.8/child-year, and the average number of diarrheal days was 3.7
      days/child-year over an average observation period of 2.8 years/child. Seventy
      five percent of the diarrheal episodes were < or = 2 days in duration. Persistent
      diarrhea was relatively uncommon (0.2% of the children) and chronic diarrhea was
      observed in only one episode. Compared with malnourished and/or stunted children,
      better-nourished children experienced significantly fewer diarrheal episodes. The
      diarrheal incidence rate for children with blood group A was significantly less
      that that of the children with blood groups O and AB. The most frequent bacterial
      enteropathogens isolated from diarrheal stool specimens were enterotoxigenic
      Escherichia coli (9%) and Aeromonas species (9%), followed by Plesimonas
      shigelloides (4%) and Shigella flexneri (3.8%). Rotavirus was the most common
      viral agent isolated from diarrheal stool samples (5%). Giardia lamblia,
      Cryptosporidium parvum, and E. histolytica were identified in 11%, 8.4%, and 8%,
      respectively, of the diarrheal stool specimens. Dysentery was observed in 7.7% of
      all diarrheal episodes. The most common pathogens isolated from dysenteric stool
      were S. flexneri (11.6%), Aeromonas sp. (10%), E. histolytica (8.7%),
      Campylobacter jejunii (5.8%), P. shigelloides (4.3%), and A. caviae (4.3%). The
      overall incidence rate of E. histolytica-associated diarrhea was 0.08/child-year.
      Visible blood and hemoccult test-detected blood loss was found in 7% and 25%,
      respectively, of cases of E. histolytica-associated diarrhea. Children who had
      recovered from a diarrheal episode with E. histolytica, but not E. dispar, had
      half the chance of developing subsequent E. histolytica-associated diarrhea,
      consistent with the development of species-specific acquired immunity. In
      conclusion, the use of modern diagnostic tests demonstrated that E. histolytica
      contributed to overall morbidity from diarrheal illness. Understanding the
      etiology, frequency, and consequences of acute diarrhea in children from a
      developing country should aid in the design of interventions to improve child
      health.

PMID- 14640501
TI  - Frequency and virulence properties of diarrheagenic Escherichia coli in children
      with diarrhea in Gabon.
AB  - To investigate the presence of diarrheagenic Escherichia coli in Lambarene,
      Gabon, 150 children with diarrhea were screened for enteroaggregative E. coli
      (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC),
      enterohemorrhagic E. coli (EHEC), and enteroinvasive E. coli (EIEC) using
      polymerase chain reaction and an HEp-2 cell culture techniques. Isolates of EAEC
      were detected in 57 children, two thirds of them between six months and two years
      of age, and isolates of ETEC were detected in seven patients. Isolates of EPEC,
      EHEC, and EIEC were not present in this population. Among the EAEC, the pCVD432
      plasmid, a heat stable (ST)-like (ST-like) enterotoxin (EAST), and a plasmid
      encoded heat-labile toxin (PET) were detected in 19, 34, and 42 cases,
      respectively. Detection of pCVD432, EAST, and PET were significantly associated
      with EAEC identified by the HEp-2 cell assay. Although detected only in 16
      patients, the presence of the fimbriae AAF I (aagA) and AAF II (aafA) were more
      likely to occur in EAEC than in non-EAEC (odds ratio [OR] = 4.1, 95% confidence
      interval [CI] = 0.5-38.6, and OR = 2.3, 95% CI = 1.0-5.3, respectively). The EAEC
      isolates exhibited decreased susceptibility for ampicillin, tetracycline, and
      trimethoprim.

PMID- 14640502
TI  - A randomized controlled trial of household-based flocculant-disinfectant drinking
      water treatment for diarrhea prevention in rural Guatemala.
AB  - We conducted a study to determine if use of a new flocculant-disinfectant home
      water treatment reduced diarrhea. We randomly assigned 492 rural Guatemalan
      households to five different water treatment groups: flocculant-disinfectant,
      flocculant-disinfectant plus a customized vessel, bleach, bleach plus a vessel,
      and control. During one year of observation, residents of control households had
      4.31 episodes of diarrhea per 100 person-weeks, whereas the incidence of diarrhea
      was 24% lower among residents of households receiving flocculant-disinfectant,
      29% lower among those receiving flocculant-disinfectant plus vessel, 25% lower
      among those receiving bleach, and 12% lower among households receiving bleach
      plus vessel. In unannounced evaluations of home drinking water, free chlorine was
      detected in samples from 27% of flocculant-disinfectant households, 35% of
      flocculant-disinfectant plus vessel households, 35% of bleach households, and 43%
      of bleach plus vessel households. In a setting where diarrhea was a leading cause
      of death, intermittent use of home water treatment with flocculant-disinfectant
      decreased the incidence of diarrhea.

PMID- 14640503
TI  - Interactions between Schistosoma haematobium and human immunodeficiency virus
      type 1: the effects of coinfection on treatment outcomes in rural Zambia.
AB  - A prospective cohort study was conducted in two villages in Zambia to compare the
      efficacy of praziquantel in the treatment of schistosomiasis haematobium in
      people with and without concomitant infection with human immunodeficiency virus
      (HIV). Five hundred seven individuals with infected with Schistosoma haematobium
      were enrolled and followed-up for as long as 12 months after treatment with a
      single dose of praziquantel. Seventy-three were coinfected with HIV. The study
      demonstrated that praziquantel is still very effective in the treatment and
      control of S. haematobium even when there is coinfection with HIV (without
      symptoms and signs of acquired immunodeficiency syndrome [AIDS]/HIV disease).
      Resistance to reinfection with S. haematobium is not altered in subjects
      coinfected with HIV (without symptoms and signs of AIDS/HIV disease). Individuals
      with coinfection excreted fewer eggs and complained less of hematuria than those
      without HIV infection, and the sensitivity and positive predictive value of
      reported hematuria as an indication of heavy infection were lower in the group
      coinfected with HIV. This observation may have implications for the use of
      hematuria as an indicator for rapid diagnosis of schistosomiasis in areas where
      HIV is prevalent.

PMID- 14640504
TI  - Hyperendemic fascioliasis associated with schistosomiasis in villages in the Nile
      Delta of Egypt.
AB  - Coprologic surveys were carried out in villages of the Behera Governorate in the
      Nile Delta region of Egypt to characterize the epidemiologic features of human
      fascioliasis caused by Fasciola hepatica and F. gigantica in this lowland endemic
      area by comparison with fascioliasis caused by only F. hepatica in areas
      hyperendemic for human disease in the Andean highlands of South America. The
      fascioliasis prevalences detected (range = 5.2-19.0%, mean = 12.8%) are the
      highest obtained in Egypt. The comparison with previous results suggests that in
      the Nile Delta, fascioliasis is spreading from an original situation of sporadic
      human cases in well-known endemic foci for animal disease to an endemic
      distribution in humans, which may be characterized as a mesoendemic region that
      includes several hyperendemic areas for human disease. As in Andean countries, a
      relationship with sex was found, although in Egypt prevalences, but not
      intensities, appeared to be significantly higher in females. All ages appear to
      be susceptible to liver fluke infection, with prevalences and intensities being
      lower before and after school age, a situation that is consistent with that
      detected in Andean countries, although the peak in the 9-11-year-old age group
      appears less pronounced in Egypt. The intensities were very high when compared
      with those found in subjects sporadically infected in areas endemic for animal
      disease, but relatively low for a hyperendemic situation, although the
      intensities may not be conclusive because of the transmission seasonality of
      fascioliasis in the Nile Delta. The marked similarities in the qualitative and
      quantitative spectrums of protozoans and helminths, multiparasitisms, and
      associations between liver flukes and other parasitic species suggest
      physiographic-hydrographic and behavioral-social characteristics similar in all
      areas hyperendemic for human fascioliasis, which are independent of other factors
      such as climate, altitude, and cultural or religious features. The significant
      positive association between liver fluke infection and schistosomiasis mansoni
      detected in one locality has never been described elsewhere, and must be
      considered relevant from clinical, pathologic, diagnostic, and therapeutic points
      of view. Interestingly, the relationships of schistosomiasis prevalences and
      intensities with sex and age follow patterns similar to those found in
      fascioliasis.

PMID- 14640505
TI  - Prevalence of antibodies to unique Taenia solium oncosphere antigens in taeniasis
      and human and porcine cysticercosis.
AB  - The presence of two oncosphere antigens (OAs) of 22.5 and 31.3 kD in whole and
      excretory/secretory (ES) OA preparations of both Taenia solium and T. saginata or
      in antigen preparations from T. solium metacestodes or immature tapeworms was
      assessed. This included an evaluation of whether antibodies to other cestodes
      cross-reacted to these OAs. The OAs were present in whole oncosphere extract and
      E/S antigens of T. solium, but were not present in other stages (immature
      tapeworm or metacestode) or in OAs of T. saginata. The majority (95%) of T.
      solium tapeworm carriers had antibodies to these OAs, while only 20% of active
      neurocysticercosis cases were positive. No antibodies to the OAs were found in
      healthy controls, subjects infected with Hymenolepis nana, patients with hydatid
      disease, T. saginata tapeworm carriers, hamsters infected with immature T. solium
      tapeworms, or dogs infected with Echinococcus granulosus. The OAs are stage and
      species specific to T. solium and antibodies to OAs are usually present in
      tapeworm carriers.

PMID- 14640506
TI  - Short report: Identification of Echinococcus species from a yak in the Qinghai
      Tibet plateau region of China.
AB  - The species identification of an echinococcal lesion in the liver of a yak in the
      Qinghai-Tibet plateau region of China, where both Echinococcus granulosus and E.
      multilocularis are present, was difficult to determine because of the atypical
      appearance of the lesion. Polymerase chain reaction-based mitochondrial
      genotyping allowed us to discriminate the Echinococcus species. Nucleotide
      sequences of the cytochrome c oxidase subunit 1 (cox1) and cytochrome b (cytb)
      genes amplified from the echinococcal lesion demonstrated that the yak was
      infected with the E. granulosus G1 genotype (sheep strain).

PMID- 14640507
TI  - Mother-to-child transmission of human immunodeficiency virus type 1 in relation
      to the season in Yaounde, Cameroon.
AB  - A public health program to prevent mother-to-child transmission (MTCT) of human
      immunodeficiency virus type 1 (HIV-1) by treatment with nevirapine has been
      ongoing in Yaounde, Cameroon since January 2000. After 24 months, plasma samples
      from 119 children born to HIV-1-positive mothers were tested for HIV-1 RNA
      between six and eight weeks after birth. Thirteen (10.9%) tested positive (95%
      confidence interval = 5.2-16.7%). Risk factors associated with MTCT in this study
      were maternal viral load (P < 0.05), low birth weight (chi2 for trend = 8.78, P =
      0.01), and birth during the second half of the year. A high correlation was
      repeatedly observed between rainfall in a given month and the risk of MTCT of HIV
      1 in children born three months later (r = 0.634, P < 0.001). Although we cannot
      rule out other tropical infections related to the rainy season, the role of
      malaria is highly suspected since the interval of three months we observed
      between the peaks of rainfall and the rate of transmission is consistent with the
      Plasmodium life cycle.

PMID- 14640508
TI  - Short report: Serodiagnosis of plague in humans and rats using a rapid test.
AB  - Serodiagnosis of plague is very useful for its retrospective confirmation and for
      epidemiologic studies in humans and in rodents, since rats constitute the main
      natural reservoir of Yersinia pestis. We have developed a rapid test for the
      detection of IgG antibodies to fraction 1 (F1) based on immunochromatography and
      protein A to detect both human and rat IgG. When tested with reference human sera
      (35 positive and 37 negative), this assay showed a sensitivity of 94.3% and a
      specificity of 89.2%. When Rattus rattus and R. norvegicus reference sera (22
      positive and 24 negative) were used, the sensitivity was 100% and the specificity
      was 91.7%. This simple serodiagnostic tool is of great potential value in the
      surveillance of plague. As far as we know, this test is the first of its kind
      designed for diagnosis of both humans and animals.

PMID- 14640509
TI  - Saponins and flavonoids of Allium triquetrum.
AB  - A phytochemical investigation of the flowers and bulbs of Allium triquetrum has
      been undertaken, leading to the isolation of five new furostanol saponins,
      triquetrosides A1/A2 (1a/1b), B (3), and C1/C2 (4a/4b), from the flowers, along
      with ascalonisides A1/A2 (6a/6b). The 22-O-methyl derivatives of triquetrosides
      A1/A2 (2a and 2b) and C1/C2 (5a and 5b) were also isolated, but they are
      considered extraction artifacts. Large amounts of seven kaempferol glycosides, of
      which one (7) has a new structure, were also isolated from both flowers and
      bulbs. The structures of the new compounds were determined by spectral and
      chemical methods.

PMID- 14640510
TI  - Briarlides, briarane diterpenes from a gorgonian Briareum sp.
AB  - New briarane diterpenes, briarlides A-H (1-8), have been isolated from a
      gorgonian Briareum sp., collected at Amami Oshima, Kagoshima Prefecture. Their
      structures and cytotoxity toward Vero and MDCK cells are described.

PMID- 14640511
TI  - Antitumor agents. 228. five new agarofurans, Reissantins A-E, and cytotoxic
      principles from Reissantia buchananii.
AB  - Twenty-one compounds, including five new agarofuran sesquiterpenes, reissantins A
      E (1-5), were isolated from Reissantia buchananii by means of bioassay-directed
      fractionation and their structures identified from spectral data. Reissantins A-C
      are the first reported simple agarofuran sesquiterpenes to contain a 5-carboxy-N
      methyl-2-pyridone (CNMP) substituent, which has previously been found only in
      macroring agarofuran pyridine alkaloids. The major terpenoid components,
      celastrol (6) and its methyl ester derivative, pristimerin (7), were
      significantly active against nine cancer cell lines, including A549, MCF-7, HCT
      8, KB, KB-VIN, U-87-MG, PC-3, 1A9, and PTX10 cell lines, with ED(50) values
      ranging from 0.076 to 0.34 microg/mL.

PMID- 14640512
TI  - Dibenzylbutyrolactone and dibenzylbutanediol lignans from Peperomia duclouxii.
AB  - Nine new lignans (1-9), including five dibenzylbutyrolactones and four
      dibenzylbutanediols, were obtained from an ethyl acetate extract of the whole
      plants of Peperomia duclouxii. The structures of 1-9 were determined by
      spectroscopic methods (mainly extensive 1D and 2D NMR experiments and by mass
      spectral measurements). The absolute structures were elucidated as 2S,3S from
      their optical rotations and by chemical transformations.

PMID- 14640513
TI  - Constituents of the Vietnamese medicinal plant Streptocaulon juventas and their
      antiproliferative activity against the human HT-1080 fibrosarcoma cell line.
AB  - The methanolic extract of roots of Streptocaulon juventas, having shown strong
      antiproliferative activity against the highly metastatic human HT-1080
      fibrosarcoma cell line, was subjected to activity-guided isolation to yield 16
      cardenolides including five new ones, acovenosigenin A 3-O-beta
      digitoxopyranoside (1), digitoxigenin gentiobioside (2), digitoxigenin 3-O-[O
      beta-glucopyranosyl-(1-->6)-O-beta-glucopyranosyl-(1-->4)-3-O-acetyl-beta
      digitoxopyranoside] (3), digitoxigenin 3-O-[O-beta-glucopyranosyl-(1-->6)-O-beta
      glucopyranosyl-(1-->4)-O-beta-digitalopyranosyl-(1-->4)-beta-cymaropyranoside]
      (4), and periplogenin 3-O-(4-O-beta-glucopyranosyl-beta-digitalopyranoside) (5),
      and two new hemiterpenoids, (4R)-4-hydroxy-3-isopropylpentyl beta-rutinoside (6)
      and (R)-2-ethyl-3-methylbutyl beta-rutinoside (7), together with two known
      phenylpropanoids and a known phenylethanoid. The isolated cardenolides strongly
      inhibited the proliferation of the HT-1080 cell line (IC(50) values, 54-1600 nM).

PMID- 14640514
TI  - Isolation and structures of new halogenated prostanoids from the Okinawan soft
      coral Clavularia viridis.
AB  - Fifteen new halogenated prostanoids 9-23 were isolated as minor constituents from
      the Okinawan soft coral Clavularia viridis. Compounds 9-11 were new members of
      iodovulone, and compounds 12-18 were 12-O-acetyliodovulones, 12-O
      acetylbromovulones, and 12-O-acetylchlorovulones. Compounds 19-23 were 10,11
      epoxy congeners of iodovulone, bromovulone, and chlorovulone. The structures of
      these compounds were determined on the basis of spectroscopic analysis and
      chemical conversion.

PMID- 14640515
TI  - Chemistry of renieramycins. Part 3.(1) isolation and structure of stabilized
      renieramycin type derivatives possessing antitumor activity from Thai sponge
      Xestospongia species, pretreated with potassium cyanide.
AB  - Renieramycins M (1m) and N (1n) were isolated from the Thai sponge Xestospongia
      sp., pretreated with potassium cyanide in methanolic buffer solution, and their
      structures and relative stereochemistries were elucidated on the basis of
      spectroscopic data. This strategy is the first example of the gram-scale
      preparation of this series of compounds and presents a potential solution for
      increasing the gram-scale supply of novel natural products from marine sources.

PMID- 14640516
TI  - Flavonoids from Dalbergia louvelii and their antiplasmodial activity.
AB  - Four new flavonoids (1-4), along with 13 known compounds, were isolated from the
      heartwood of Dalbergia louvelii by following their potential to inhibit in vitro
      the growth of Plasmodium falciparum. Of the isolated compounds, four known
      compounds showed antiplasmodial activity with IC(50) values ranging from 5.8 to
      8.7 microM, namely, (R)-4' '-methoxydalbergione (5), obtusafuran (6), 7,4'
      dihydroxy-3'-methoxyisoflavone (7), and isoliquiritigenin (8). The structures of
      the new compounds were determined using spectroscopic techniques as 1-(3
      hydroxyphenyl)-3-(4-hydroxy-2,5-dimethoxyphenyl)propane (1), spirolouveline (2),
      (3R)-7,2'-dihydroxy-4',5'-dimethoxyisoflavanone (3), and 3-(2,4-dihydroxy-5
      methoxy)phenyl-7-hydroxycoumarin (4), respectively.

PMID- 14640517
TI  - New cytotoxic sesterterpenoids and norsesterterpenoids from two sponges of the
      genus Sarcotragus.
AB  - New norsesterterpenoids (3 and 4), a sesterterpenoid (6), pyrroloterpenoids (7
      10), and a stereoisomer of kurospongin (5) were isolated, along with known
      furanosesterterpenes (11-15), from two marine sponges of the genus Sarcotragus.
      The gross structures were established on the basis of NMR and MS analysis. The
      stereochemistry was defined by combined use of NMR and CD spectroscopy. The
      compounds were evaluated for cytotoxicity against five human tumor cell lines and
      were found to exhibit marginal to moderate activity.

PMID- 14640518
TI  - Characterization of an anti-tuberculosis resin glycoside from the prairie
      medicinal plant Ipomoea leptophylla.
AB  - The organic soluble extract from the leaves of the native North American prairie
      plant Ipomoea leptophylla (big root morning glory) showed in vitro activity
      against M. tuberculosis. Bioassay-guided fractionation of this extract resulted
      in the identification of two new resin glycosides (6, 7). Base-catalyzed
      hydrolysis of these glycosides gave operculinic acid (1) as the glycosidic acid
      component as well as trans-cinnamic acid, propanoic acid, and lauric acid. The
      complete structure elucidation was accomplished through derivatization, 1D and 2D
      NMR spectroscopy (TOCSY, ROESY, HSQC, HMBC), and MS/MS experiments on 6 and 7 as
      well as the permethylated derivative 8.

PMID- 14640519
TI  - A new acylated oleanane triterpenoid from Couepia polyandra that inhibits the
      lyase activity of DNA polymerase beta.
AB  - Bioassay-directed fractionation of a n-hexane extract of Couepia polyandra using
      an assay to detect inhibitors of the lyase activity of DNA polymerase beta
      resulted in the isolation of the new triterpene 3beta,16beta,23-triacetoxyolean
      12-en-28-oic acid (1) and four known compounds, oleanolic acid, betulinic acid,
      stigmasterol, and beta-sitosterol. The structure of the new compound was
      established on the basis of extensive 1D and 2D NMR spectroscopic interpretation.
      All five compounds inhibited DNA polymerase beta lyase activity.

PMID- 14640520
TI  - Stereochemistry of kahalalide F.
AB  - The stereochemistry of the amino acids in the marine-derived cyclic depsipeptide
      kahalalide F has been defined by a series of degradation reactions (hydrolysis,
      ozonolysis, Edman degradation, and Marfey derivatization), yielding smaller
      fragments of the marine natural product. The results from these reactions agree
      with the structure originally proposed by Hamann and Scheuer and with the same
      stereochemistry of most of the component amino acids more recently proposed by
      Goetz, Yoshida, and Scheuer. However, our assignments of d-Val(3) and l-Val(4)
      are the reverse of previous assignments made as l-Val(3) and d-Val(4). The
      present (reversed) stereochemistry is crucial for the antitumor activity of
      kahalalide F.

PMID- 14640521
TI  - 15,21-Cyclowithanolides from Jaborosa bergii.
AB  - Six new withanolides (1-6) were isolated from the aerial parts of Jaborosa bergii
      plants and characterized by spectroscopic methods (1D and 2D NMR, MS). Five of
      the new compounds presented a novel norbornane-type structure in ring D of the
      steroid nucleus (1-5), resulting from a carbon-carbon bond between C-15 and C-21.
      The sixth withanolide isolated was the 5alpha-chloro-6beta-hydroxy analogue (6)
      of 2,3-dehydrojaborosalactol M (7), previously isolated from this plant. Compound
      1 showed selective phytotoxicity toward monocotiledoneous and dicotiledoneous
      species.

PMID- 14640522
TI  - Sunpollenol and five other rearranged 3,4-seco-tirucallane-type triterpenoids
      from sunflower pollen and their inhibitory effects on Epstein-Barr virus
      activation.
AB  - Six new rearranged 3,4-seco-tirucallane-type triterpenoids (1-6) have been
      isolated from the diethyl ether extract of the pollen grains of sunflower
      (Helianthus annuus). These compounds were evaluated with respect to their
      inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA)
      induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji
      cells. All of the compounds tested showed potent inhibitory effects on EBV-EA
      activation (97-100% inhibition at 1 x 10(3) mol ratio/TPA).

PMID- 14640523
TI  - New minor taxane derivatives from the needles of Taxus canadensis.
AB  - Seven minor taxane derivatives were isolated for the first time from the needles
      of Taxus canadensis. Four of these natural taxanes are O-glycosylated (1-4), with
      4 being the only reported taxane with a glucose on ring C, and two have a
      dimethylamino-C-5 side chain (5 and 6). An unusual double bond at C-5(6) has been
      identified in taxane 7.

PMID- 14640524
TI  - Enhancement of the antiplasmodial activity of quassin by transformation into a
      gamma-lactone.
AB  - The naturally occurring bitter principle quassin (1) was converted chemically
      into the gamma-lactone quassilactone (13) in an attempt to enhance its
      antiplasmodial activity. The in vitro antiplasmodial activity of 13 against
      Plasmodium falciparum (K1) (IC(50) = 23 microM) was 40-fold greater than that of
      1. However, one of the intermediates, compound 8, the 15beta-hydroxy,16-O-m
      chlorobenzoyl analogue of 1, was 506-fold more active than 1 against P.
      falciparum (IC(50) = 1.8 microM) and only 3-fold less potent than chloroquine. In
      addition, 8 displayed the best cytotoxic/antiplasmodial ratio (112) of all of the
      compounds tested. In the course of this work a dimer, neoquassin ether (6),
      linked at C-16 was also prepared; 6 was found to have weak antiplasmodial
      activity (IC(50) = 9.7 microM).

PMID- 14640525
TI  - Crambescidin 826 and dehydrocrambine A: new polycyclic guanidine alkaloids from
      the marine sponge Monanchora sp. that inhibit HIV-1 fusion.
AB  - Two new polycyclic guanidine alkaloids, crambescidin 826 (1) and dehydrocrambine
      A (2), and the known compounds crambescidin 800 (3) and fromiamycalin (4) were
      isolated from the marine sponge Monanchora sp. The structures of 1 and 2 were
      elucidated by 2D NMR and mass spectrometry, and relative stereochemistry was
      established by analysis of coupling constants and ROESY spectra. The pentacyclic
      guanidine alkaloids 1, 3, and 4 inhibit HIV-1 envelope-mediated fusion in vitro
      with IC(50)'s of 1-3 microM, while compound 2, a tricyclic guanidine alkaloid,
      showed weaker inhibition, with an IC(50) of approximately 35 microM.

PMID- 14640526
TI  - New bromotyrosine derivatives from an association of two sponges, Jaspis
      wondoensis and Poecillastra wondoensis.
AB  - Three new bromotyrosine derivatives (4-6) were isolated from an association of
      two sponges, Jaspis wondoensis and Poecillastra wondoensis, along with the
      previously described (E,E)-psammaplin A (1), (E,Z)-psammaplin A (2), psammaplin D
      (3), bisaprasin (7), and (3-bromo-4-hydroxyphenyl)acetonitrile (8). The
      structures of the new compounds were established on the basis of NMR and MS
      spectroscopic analysis. The compounds 1, 3, and 5-7 displayed significant
      cytotoxicity against human lung (A549), ovarian (SK-OV-3), skin (SK-MEL-2), CNS
      (XF498), and colon (HCT15) cancer cell lines. Compounds 3-7 were further
      evaluated for antibacterial activity against methicillin- or ofloxacin-resistant
      Staphylococcus strains. Compound 4 exhibited more potent antibacterial activity
      than meropenem against several strains.

PMID- 14640527
TI  - New polyoxygenated farnesylcyclohexenones, deacetoxyyanuthone A and its hydro
      derivative from the marine-derived fungus Penicillium sp.
AB  - New polyoxygenated farnesylcyclohexenones, 7-deacetoxyyanuthone A (1) and its 2,3
      hydro derivative (2), were isolated together with the known farnesylquinones (3,
      4) from a marine isolate of the genus Penicillium. The structures of the new
      deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2) were assigned by
      spectroscopic methods, including 2D NMR and CD for the Cotton effect of alpha
      epoxyketone experiments. Compounds 1 and 3 showed moderate in vitro cytotoxicity
      in a panel of five human tumor cell lines, and 1 also exhibited mild in vitro
      antibacterial activity against methicillin-resistant and multidrug-resistant
      Staphylococcus aureus (MIC, 50 microg/mL).

PMID- 14640528
TI  - New bioactive polyphenols from Theobroma grandiflorum ("cupuacu").
AB  - Activity-guided fractionation of Theobroma grandiflorum ("cupuacu") seeds
      resulted in the identification of two new sulfated flavonoid glycosides,
      theograndins I (1) and II (2). In addition, nine known flavonoid antioxidants,
      (+)-catechin, (-)-epicatechin, isoscutellarein 8-O-beta-d-glucuronide, hypolaetin
      8-O-beta-d-glucuronide, quercetin 3-O-beta-d-glucuronide, quercetin 3-O-beta-d
      glucuronide 6' '-methyl ester, quercetin, kaempferol, and isoscutellarein 8-O
      beta-d-glucuronide 6' '-methyl ester, were identified. Theograndin II (2)
      displayed antioxidant activity (IC(50) = 120.2 microM) in the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free-radical assay, as well as weak cytotoxicity in the HCT
      116 and SW-480 human colon cancer cell lines with IC(50) values of 143 and 125
      microM, respectively. While 1 was less active as an antioxidant than 2, the known
      compounds were more potent in the DPPH assay (IC(50) range 39.7-89.7 microM).

PMID- 14640530
TI  - Chlorinated C12 fatty acid metabolites from the red alga Gracilaria verrucosa.
AB  - Three compounds containing moieties rarely encountered in nature, viz., 3
      nonyloxirane-2 carboxylic acid methyl ester (1), 2-chlorododec-2-en-1-ol (2), and
      2-chlorododec-2,11-dien-1-ol (3), were isolated from the red alga Gracilaria
      verrucosa, and their structures were determined by spectroscopic methods.

PMID- 14640529
TI  - Brominated sesquiterpenes from the red alga Laurencia obtusa.
AB  - Four new sesquiterpenes, (8R)-8-bromo-10-epi-beta-snyderol (1), (8S)-8-bromo-beta
      snyderol (2), 5-bromo-3-(3'-hydroxy-3'-methylpent-4'-enylidene)-2,4,4
      trimethylcyclohexanone (3), and the epoxide 4, have been isolated from the
      chloroform-methanol extract of Laurencia obtusa, together with the three known
      compounds alpha-snyderol (5), alpha-snyderol acetate (6), and stigmasterol. The
      structures of the isolated compounds were elucidated through spectroscopic
      analyses. Compound 1 showed antimalarial activity, with IC(50) values of 2700 and
      4000 ng/mL against the D6 and W2 clones of Plasmodium falciparum, respectively.

PMID- 14640531
TI  - New 9-thiocyanatopupukeanane sesquiterpenes from the nudibranch Phyllidia
      varicosa and its sponge-prey Axinyssa aculeata.
AB  - Two new 9-thiocyanatopupukeanane sesquiterpene isomers were isolated as major
      metabolites from the MeOH extract of the sponge Axinyssa aculeata and from its
      nudibranch predator Phyllidia varicosa. The presence of the sesquiterpenes was
      monitored by GC-MS, and the structures were confirmed by both 1D and 2D NMR
      spectroscopy. The isolated sesquiterpenes were found to be toxic toward brine
      shrimp at LC(50) of 5 ppm. At a dose level of 20 microg, they were found to be
      weakly and moderately active against B. subtilis and C. albicans, respectively.

PMID- 14640532
TI  - Cytotoxic cucurbitacin constituents from Sloanea zuliaensis.
AB  - A new cucurbitacin D analogue, 2-deoxycucurbitacin D (1), as well as cucurbitacin
      D (2) and 25-acetylcucurbitacin F (3) were isolated from Sloanea zuliaensis.
      Compound 1 was found only in the young leaves of the plant and not in the mature
      leaves, and its structure was established using spectroscopic means. Compounds 1
      3 demonstrated potent cytotoxic activity against breast (MCF-7), lung (H-460),
      and central nervous system (SF-268) human cancer cell lines.

PMID- 14640533
TI  - Sesquiterpene metabolites of the antarctic gorgonian Dasystenella acanthina.
AB  - The ethereal extract of the Antarctic gorgonian Dasystenella acanthina was found
      to contain three main nonpolar and relatively transient sesquiterpene metabolites
      (1-3), which were isolated and submitted to spectral analysis. Two of them were
      identified as the previously reported compounds trans-beta-farnesene (1) and
      isofuranodiene (3), whereas the third metabolite, the furanoeudesmane 2, was
      unknown. The structure elucidation of this new sesquiterpene was solved mainly on
      the basis of its spectral properties and correlation with known compounds.

PMID- 14640534
TI  - New indole alkaloids from the North Sea bacterium Vibrio parahaemolyticus Bio249.
AB  - Several bis- and tris-indole derivatives were isolated from a North Sea bacterium
      that was closely related to Vibrio parahaemolyticus (98% homology). 1,1,3-Tris(3
      indolyl)butane (3) is a new compound, and 3,3-bis(3-indolyl)butane-2-one (1a),
      arundine (1b), and 1,1,1-tris(3-indolyl)methane (2a) were isolated from a
      microorganism for the first time here. Additionally, many other known compounds
      were obtained from the ethyl acetate extract of the culture. Their structures
      were established on the basis of various spectral data, and their origin is
      discussed. All compounds were inactive against a range of bacteria and fungi.

PMID- 14640535
TI  - Alkaloid production in Crinum moorei cultures.
AB  - The alkaloids cherylline (1), crinamidine (2), crinine (3), epibuphanisine (4),
      lycorine (5), powelline (6), undulatine (7), 1-epideacetylbowdensine (8), and 3-O
      acetylhamayne (9) were identified in the in vitro propagated bulblets of Crinum
      moorei. In addition, crinine, powelline, and undulatine were detected in the
      solidified Murashige and Skoog (MS) medium. The identity of the alkaloids was
      confirmed by comparing retention times and mass spectra with known samples.
      Light, as well as benzyladenine (BA) and charcoal supplementation of the tissue
      culture medium, influenced the levels of specific alkaloids in both the bulblets
      and media.

PMID- 14640536
TI  - Molecular basis of neurotrophin-receptor interactions.

PMID- 14640537
TI  - Design, synthesis, and biological activity of a difluoro-substituted,
      conformationally rigid vigabatrin analogue as a potent gamma-aminobutyric acid
      aminotransferase inhibitor.
AB  - Previously it was found that a conformationally rigid analogue (2) of the
      epilepsy drug vigabatrin (1) did not inactivate gamma-aminobutyric acid
      aminotransferase (GABA-AT). A cyclic compound with an exocyclic double bond (6)
      was synthesized and was found to inactivate GABA-AT, but only in the absence of 2
      mercaptoethanol. The corresponding difluoro-substituted analogue (14) was
      synthesized and was shown to be a very potent time-dependent inhibitor, even in
      the presence of 2-mercaptoethanol.

PMID- 14640538
TI  - Synthesis and evaluation of imidazole acetic acid inhibitors of activated
      thrombin-activatable fibrinolysis inhibitor as novel antithrombotics.
AB  - Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of
      fibrinolysis, and inhibitors of this enzyme have potential use in antithrombotic
      and thrombolytic therapy. Appropriately substituted imidazole acetic acids such
      as 10j were found to be potent inhibitors of activated TAFI and selective versus
      the related carboxypeptidases CPA, CPN, and CPM but not CPB. Further, 10j
      accelerated clot lysis in vitro and was shown to be efficacious in a primate
      model of thrombosis.

PMID- 14640539
TI  - Discovery of 1-(2-aminomethylphenyl)-3-trifluoromethyl-N- [3-fluoro-2'
      (aminosulfonyl)[1,1'-biphenyl)]-4-yl]-1H-pyrazole-5-carboxyamide (DPC602), a
      potent, selective, and orally bioavailable factor Xa inhibitor(1).
AB  - Factor Xa, a serine protease, is at the critical juncture between the intrinsic
      and extrinsic pathways of the coagulation cascade. Inhibition of factor Xa has
      the potential to provide effective treatment for both venous and arterial
      thrombosis. We recently described a series of meta-substituted phenylpyrazoles
      that are highly potent, selective, and orally bioavailable factor Xa inhibitors.
      In this paper we report our efforts to further optimize the selectivity profile
      of our factor Xa inhibitors with a series of ortho- and/or para-substituted
      phenylpyrazole derivatives. The most potent compounds display sub-nanomolar
      inhibition constants for factor Xa and show greater than 1000-fold selectivity
      against other serine proteases. These compounds are also effective in a rabbit
      model of arteriovenous shunt thrombosis. Optimization of this series led to the
      preclinical development of DPC602, a 2-(aminomethyl)phenylpyrazole analogue, as a
      highly potent, selective, and orally bioavailable factor Xa inhibitor.

PMID- 14640540
TI  - Molecular model of the alpha(IIb)beta(3) integrin.
AB  - A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing
      (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the
      alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3)
      dual and selective inhibitors into the putative binding sites of
      alpha(IIb)beta(3) and alpha(v)beta(3). Since the binding sites of these integrins
      are located at the interface between the two heads of the individual subunits,
      only the alpha(IIb)beta(3) head region is modeled. The 3D conformations of two
      loops in alpha(IIb), whose residues have been implicated in non-peptide ligand
      binding, could not be determined from homology with alpha(v) alone. Mutagenesis
      data and the modeling of small ligand binding contributed to the rational design
      of these loop conformations. The final energy minimized loop conformations
      exhibit permissible phi/psi angles and contribute to a binding site model of
      alpha(IIb)beta(3) that is consistent with both the known mutagenesis studies and
      in-house structure-activity relationships. The charged residues alpha(IIb):E117
      and beta(3):R214 are found to dominate the ligand-protein binding interaction.
      The previously identified "exosite" is also identified as a hydrogen bond,
      hydrophobic or pi-pi interaction with Y190, similar to the recently proposed
      binding model of alpha(v)beta(3).

PMID- 14640541
TI  - A method for designing conformationally restricted analogues based on allylic
      strain: synthesis of a novel class of noncompetitive NMDA receptor antagonists
      having the acrylamide structure.
AB  - A series of conformationally restricted analogues of milnacipran, a weak NMDA
      receptor antagonist, were designed by a method based on allylic strain. The
      conformational analysis study showed that the allylic-strain-based conformational
      restriction indeed occurred and that the affinity for the NMDA receptor was
      efficiently improved by the conformational restriction.

PMID- 14640542
TI  - Neurosteroid analogues. 9. Conformationally constrained pregnanes: structure
      activity studies of 13,24-cyclo-18,21-dinorcholane analogues of the GABA
      modulatory and anesthetic steroids (3alpha,5alpha)- and (3alpha,5beta)-3
      hydroxypregnan-20-one.
AB  - The hydrogen-bond-acceptor properties of the carbonyl moiety in the 17beta-acetyl
      group on the D-ring of the anesthetic steroids (3alpha,5alpha)- and
      (3alpha,5beta)-3-hydroxypregan-20-one form an important part of the anesthetic
      steroid pharmacophore. 13,24-Cyclo-18,21-dinorcholanes containing a ketone or
      conjugated ketone group at C-20, C-22, C-23, or C-24 were prepared as
      conformationally constrained analogues of these anesthetic steroids and were used
      to probe for alternate locations for the D-ring hydrogen-bond-accepting carbonyl
      group. The analogues were evaluated (1). in [(35)S]-tert
      butylbicyclophosphorothionate binding experiments, (2). in electrophysiological
      experiments using rat alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in
      Xenopus laevis oocytes, and (3). as tadpole anesthetics. In the binding assay,
      the relative order of potencies for the analogues in the 5alpha- and 5beta-series
      is identical. For the ketones, the order is 24-one >or= 23-one > 20-one > 22-one.
      Likewise, for the enones, the order is delta(22)-24-one > delta(20(22))-23-one >
      delta(22)-20-one > delta(23)-22-one. Similar relative orders of potencies are
      also found in the other two bioassays. The activities of the 24-one and delta(22)
      24-one compounds were expected to be very low, because the carbonyl group in
      these compounds is located over the steroid C-ring and oriented toward C-8.
      Instead, these compounds have the highest activities in their respective series,
      with the delta(22)-24-one compounds having activities comparable to those of the
      reference anesthetic steroids. The electrophysiology results obtained with the 24
      oxo-cyclosteroids suggest that rat alpha(1)beta(2)gamma(2L) GABA(A) receptors
      contain more than one donor for the hydrogen-bond-acceptor group of anesthetic
      steroids. The family of cyclosteroids should be useful for future structure
      activity relationship studies of steroid modulation of other GABA(A) receptor
      subtypes.

PMID- 14640543
TI  - Synthesis, comparative photosensitizing efficacy, human serum albumin (site II)
      binding ability, and intracellular localization characteristics of novel
      benzobacteriochlorins derived from vic-dihydroxybacteriochlorins.
AB  - In a sequence of reactions, methyl mesopyropheophorbide a, mesochlorin e(6)
      trimethyl ester, mesochlorin p(6) trimethyl ester, mesopurpurin-18-N-hexylimide
      methyl ester, and mesopurpurin-18-N-3,5-bis(trifluoromethyl)benzylimide methyl
      ester were synthesized from chlorophyll-a. These chlorins on reacting with osmium
      tetraoxide produced the corresponding vic-dihydroxybacteriochlorins. The 8
      vinylchlorins obtained by refluxing the related vic-dihydroxybacteriochlorins in
      o-dichlorobenzene were individually treated with dimethylacetylenedicarboxylate
      (DMAD) under Diels-Alder reaction conditions. The intermediate adducts on 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) treatment rearranged to the corresponding
      stable benzobacteriochlorins, exhibiting the longest wavelength absorption in the
      range of 737 to 805 nm. In preliminary in vitro (RIF tumor cells) and in vivo
      screening (C3H/HeJ mice bearing RIF tumors), some of these compounds were found
      to be quite effective. Under similar treatment conditions (drug dose: 5.0
      micromol/kg; light dose: 135 J/cm(2), tumors were exposed to light for 30 min at
      24 h postinjection), the benzobacteriochlorins containing N-substituted-imide
      ring system produced enhanced photosensitizing efficacy with limited skin
      phototoxicity. These compounds were also found to bind to site II of human serum
      albumin (HSA). However, no correlation between the binding constant values and
      photosensitizing efficacy was observed. A competitive intracellular localization
      study of these novel structures with Rhodamine-123 (a mitochondrial probe)
      indicated their preferential localization in mitochondria, without producing any
      specific displacement of (3)H-PK11195 (PBR probe, (3)H-labeled 1-(2-chlorophenyl)
      N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide). These results suggest
      that the mitochondrial peripheral benzodiazepine receptor (PBR) is not the
      cellular binding site for this class of compounds.

PMID- 14640544
TI  - Application of the lambda-dynamics method to evaluate the relative binding free
      energies of inhibitors to HCV protease.
AB  - The lambda-dynamics method was used to calculate the relative binding free
      energies of inhibitors to the hepatitis C virus (HCV) protease. A total of seven
      HCV protease p-side product inhibitors were used in this study. The inhibitors
      are 6-mer peptides spanning P6-P1 (Ac-Asp-d-Glu-Leu-Ile-Cha-P1-CO(2)H). For this
      protein, S1 is a major hydrophobic pocket for binding. Binding of various
      residues to this pocket was investigated through free energy simulations and
      experimental inhibition constants. Several 300 ps lambda-dynamics simulations in
      explicit solvent were performed. The relative binding free energy was estimated
      from these simulations. From a single simulation, the inhibitors can be correctly
      classified into highly potent and weakly potent groups. The multiple simulations
      give an accurate rank ordering of inhibitor potency; computed and experimental
      binding free energies agree with 0.6 kcal/mol for five of the seven inhibitors.
      In addition, free energy perturbation (FEP) calculations were carried out to
      validate the results from lambda-dynamics. A total of 6 ligand pairs were
      compared. For each pair, 5-11 windows were used to map one ligand to the other.
      The cumulative simulation time was over 2 ns for each ligand pair. For four of
      the six ligand pairs, the lambda-dynamics free energy difference fits better than
      the FEP difference to the experimental value. The fact that the lambda-dynamics
      method achieved similar results in only a fraction of the total simulation time
      for FEP further demonstrates the robustness of the lambda-dynamics method.

PMID- 14640545
TI  - Characterization of the 5-HT(7) receptor. Determination of the pharmacophore for
      5-HT(7) receptor agonism and CoMFA-based modeling of the agonist binding site.
AB  - On the basis of a set of 20 diverse 5-HT(7) receptor agonists, the pharmacophore
      for 5-HT(7) receptor agonism was determined. Additionally two CoMFA models were
      developed, based on different alignments of the agonists. Both models show good
      correlations between experimental and predictive pK(i) values and show a high
      degree of similarity. The CoMFA fields were subsequently used to map the agonist
      binding site of the model of the 5-HT(7) receptor. Important roles in ligand
      binding are attributed to Asp162 of TM3 (interaction with a protonated nitrogen),
      and Thr244 of TM5 (interaction with a substituent at an aromatic moiety). Amino
      acid residues of the aromatic cluster of TM6 are hypothesized to play an
      important role in ligand binding as pi-pi stacking moieties. Agonists missing a
      hydrogen-bond-accepting moiety, but possessing an aromatic substituent instead,
      seem to bind the receptor with high affinity as well by occupying a lipophilic
      pocket hosted by residues of TM5 and TM6.

PMID- 14640546
TI  - A new class of potent vascular endothelial growth factor receptor tyrosine kinase
      inhibitors: structure-activity relationships for a series of 9-alkoxymethyl-12-(3
      hydroxypropyl)indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-ones and the identification
      of CEP-5214 and its dimethylglycine ester prodrug clinical candidate CEP-7055.
AB  - A series of potent vascular endothelial growth factor R2 (VEGF-R2) tyrosine
      kinase inhibitors from a new indenopyrrolocarbazole template is reported. The
      structure-activity relationships for a series of 9-alkoxymethyl-12-(3
      hydroxypropyl)indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-ones revealed an optimal R9
      substitution with ethoxymethyl 19 (VEGF-R2 IC(50) = 4 nM) and isopropoxymethyl 21
      (VEGF-R2 IC(50) = 8 nM) being the most potent inhibitors in the series. The VEGF
      R2 activity was reduced appreciably by increasing the size of the R9 alkoxy group
      or by alpha-methyl branching adjacent to the ring. The combined R9 alkoxymethyl
      and N12 hydroxypropyl substitutions were required for potent VEGF-R2 activity,
      and the corresponding thioether analogues were weaker than their ether
      counterparts. Compound 21 (R9 isopropoxymethyl, CEP-5214) was identified as a
      potent, low-nanomolar pan inhibitor of human VEGF-R tyrosine kinases, displaying
      IC(50) values of 16, 8, and 4 nM for VEGF-R1/FLT-1, VEGF-R2/KDR, and VEGF-R3/FLT
      4, respectively, with cellular activity equivalent to the isolated enzyme
      activity. Compound 21 exhibited good selectivity against numerous tyrosine and
      serine/threonine kinases including PKC, Tie2, TrkA, CDK1, p38, JNK, and IRK. To
      increase water solubility and oral bioavailability, the N,N-dimethylglycine ester
      40 was prepared. In pharmacokinetic studies in mice and rats, increased plasma
      levels of 21 were observed after oral administration of 40. Compound 21
      demonstrated significant in vivo antitumor activity in numerous tumor models and
      was advanced into phase I clinical trials as the water-soluble N,N
      dimethylglycine ester prodrug 40 (CEP-7055).

PMID- 14640547
TI  - An alpha helix conformationally restricted peptide is recognized by cervical
      carcinoma patients' sera.
AB  - Human papillomavirus type 16 (HPV-16) represents the major cervical carcinoma
      associated virus among women, especially in Colombia. It has thus become
      important to develop reliable inexpensive tests for detecting the presence of
      this virus. It has been shown that HPV16-E7 oncoprotein structural features have
      three alpha-helical structures and a loop-like structure. The hydrazone link
      approach was used to mimic helix secondary substructures. Sera from women with
      invasive cervical carcinoma were tested against conformationally restricted
      peptides and their respective linear peptides to identify conformational
      epitopes. One peptide that was conformationally restricted to an alpha-helix
      showed very strong positive reaction with sera from women having invasive
      cervical carcinoma; there was no reaction with sera from patients with other
      carcinomas, children, or healthy women. NMR studies confirmed this peptide's
      alpha-helical structure. The observation that constrained protein substructure
      peptidomimetics can identify new conformationally sensitive antibodies in
      cervical carcinoma patients' sera is very important, since these antibodies are
      almost all generated by native proteins, providing a new selection of antibodies
      for diagnostic and vaccine studies.

PMID- 14640548
TI  - Anticancer activity of phenolic acids of natural or synthetic origin: a structure
      activity study.
AB  - Several phenolic acids-caffeic and gallic acid derivatives-were synthesized and
      screened for their potential antiproliferative and cytotoxic properties, in
      different human cancer cell lines: mammary gland and cervix adenocarcinomas and
      lymphoblastic leukemia. The selected phenols were structurally related, which
      allowed us to gather important information regarding the structure-activity
      relationships underlying the biological activity of such compounds. This is
      proposed to be due to a balance between the antioxidant and pro-oxidant
      properties of this kind of agent. Distinct effects were found for different cell
      lines, which points to a significant specificity of action of the drugs tested.
      It was verified, for the types of cancer investigated, that the trihydroxylated
      derivatives yielded better results than the dihydroxylated ones. Tests in
      noncancerous cells, human lung fibroblasts, were also undertaken, in view of
      determining the toxic side effects of the compounds studied.

PMID- 14640549
TI  - New lupane derived compounds with pro-apoptotic activity in cancer cells:
      synthesis and structure-activity relationships.
AB  - Cellular screening of various synthetic triterpenoid compounds formally derived
      from lupane has identified a number of analogues as potential anticancer drug
      candidates. Here we describe the synthesis and structure-activity relationships
      of betulin and betulinic acid derivatives containing an E-ring modified with
      different oxygen functions. Thus compounds containing the lup-18-en-21-one, lup
      18-ene-21,22-dione, 18,19-secolupane, and the highly oxygenated 18,19-secolupane
      systems, as well as des-E-lupane derivatives, were prepared from the readily
      available natural pentacyclic triterpene betulin using oxidative procedures.
      These compounds were named betulinines. We demonstrate that only selected
      compounds, particularly those containing a lupane E-ring-derived unsaturated
      ketone or diketone function, possessed in vitro cytotoxic activity against tumor
      cell lines, suggesting a structure-activity relationship.

PMID- 14640550
TI  - Pyrazole and isoxazole derivatives as new, potent, and selective 20-hydroxy
      5,8,11,14-eicosatetraenoic acid synthase inhibitors.
AB  - In a previous paper, we reported the N-hydroxyformamidine derivative HET0016 as a
      potent and selective 20-HETE synthase inhibitor. Despite its attraction as a
      potential therapeutic agent for cerebral diseases, the preparation of an
      injectable formulation of HET0016 was limited by its poor solubility under
      neutral conditions and instability under acidic conditions. The instability of
      HET0016 in acidic conditions is due to the N-hydroxyformamidine moiety, which is
      considered to be essential for the potent and selective activity seen in our
      previous study. The activity was maintained when the N-hydroxyformamidine moiety
      was replaced by an imidazole ring (3a; IC(50) = 5.7 +/- 1.0 nM), but this was
      associated with a loss of selectivity for cytochrome p450s (CYPs). However, other
      azole derivatives such as isoxazole derivative 23 (IC(50) value 38 +/- 10 nM) and
      pyrazole derivative 24 (IC(50) value 23 +/- 12 nM) showed potent and selective
      activities with improved stability.

PMID- 14640551
TI  - 1,2-benzisoxazole phosphorodiamidates as novel anticancer prodrugs requiring
      bioreductive activation.
AB  - Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of
      phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of
      1,2-benziosoxazole moiety is expected to result in the formation of imine
      intermediate due to the cleavage of the N-O bond. The imine should then be
      spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base
      catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the
      proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than
      control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon
      incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12
      underwent extensive NADPH-dependent metabolism with concomitant generation of
      alkylating activity under both hypoxic and oxic conditions. Corresponding ketone
      metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its
      ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF
      525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction,
      incubation of 15 with rat or human p450 reductase microsomes showed moderate
      generation of 16. Microsomal cytochrome p450 and/or p450 reductase appear to be
      involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as
      well as oxic conditions.

PMID- 14640552
TI  - Synthesis and biological evaluation of 4-arylcoumarin analogues of
      combretastatins.
AB  - A series of A-ring polymethoxylated neoflavonoids was prepared by ligand coupling
      reactions involving either Suzuki or Stille reactions. Cytotoxicity studies
      indicated a potent activity against a CEM leukemia cell line for the compounds
      presenting a substitution pattern related to that of combretastatin A-4. The two
      compounds having a 3'-OH and a 4'-OCH(3) substituents on the 4-phenyl B-ring have
      no effect on human topoisomerases I and II but potently inhibit, in vitro,
      microtubule assembly. At the cell level, the active compounds were characterized
      as proapoptotic agents, but they can also trigger cell death via a nonapoptotic
      pathway.

PMID- 14640553
TI  - Synthesis and structure-activity relationships of conformationally constrained
      histamine H(3) receptor agonists.
AB  - Immepip, a conformationally constrained analogue of the histamine congener
      imbutamine, shows high affinity and functional activity on the human H(3)
      receptor. Using histamine and its homologues as prototypes, other rigid analogues
      containing either a piperidine or pyrrolidine ring in the side chain were
      synthesized and tested for their activities at the human H(3) receptor and the
      closely related H(4) receptor. In the series of piperidine containing analogues,
      immepip was found to be the most potent H(3) receptor agonist, whereas its
      propylene analogue 13a was identified as a high-affinity neutral antagonist for
      the human H(3) receptor. Moreover, replacement of the piperidine ring of immepip
      by a pyrrolidine ring led to a pair of enantiomers that show a distinct
      stereoselectivity at the human H(3) and H(4) receptor.

PMID- 14640554
TI  - N(alpha)-imidazolylalkyl and pyridylalkyl derivatives of histaprodifen: synthesis
      and in vitro evaluation of highly potent histamine H(1)-receptor agonists.
AB  - A novel series of N(alpha)()-imidazolylalkyl and pyridylalkyl derivatives of
      histaprodifen (6, 2-[2-(3,3-diphenylpropyl)imidazol-4-yl]ethanamine) was
      synthesized and evaluated as histamine H(1)-receptor agonists. The title
      compounds displayed partial agonism at contractile H(1)-receptors of guinea pig
      ileum and were at least equipotent with histamine. Agonist effects of the new
      derivatives were susceptible to blockade by the H(1)-receptor antagonist
      mepyramine (2-100 nM). In the imidazole series, suprahistaprodifen (51, [2-[2
      (3,3-diphenylpropyl)-1H-imidazol-4-yl]ethyl]-[2-(1H-imidazol-4-yl)ethyl]amine,
      N(alpha)-2-[(1H-imidazol-4-yl)ethyl]histaprodifen) showed the highest H(1)
      receptor agonist potency ever reported in the literature (pEC(50) 8.26, efficacy
      E(max) 96%). Elongation of the alkyl spacer from ethyl to butyl decreased
      activity from 3630% (ethyl, 51) to 163% (butyl, 53) of histamine potency. The
      exchange of the terminal imidazole nucleus for a pyridine ring resulted in
      compounds with comparably high potency. A decrease in agonist potency and
      efficacy was observed when the attachment of the alkyl spacer was consecutively
      changed from the ortho to the meta and the para position, respectively, of the
      pyridine ring. The pyridine series that contained a butyl chain possessed the
      highest potency and affinity. N(alpha)-[4-(2-pyridyl)butyl]histaprodifen (56)
      emerged as a strong partial agonist, being almost equipotent with 51 (pEC(50)
      8.16, E(max) 89%). Compounds 51 and 56 also showed potent partial agonism at
      contractile H(1) receptors in guinea pig aorta and potently activated H(1)
      receptor-mediated endothelium-dependent relaxation in the rat aorta. Compounds 51
      65 displayed low to moderate affinity at H(2), H(3), and M(3) receptors in
      functional models of guinea pig. Collectively, N(alpha)-imidazolylalkyl- and
      N(alpha)-pyridylalkyl-substituted histaprodifens represent a novel class of
      potent H(1)-receptor agonists. These compounds may be useful to define the
      (patho)physiological role of the H(1)-receptor and refine molecular models of
      H(1)-receptor activation.

PMID- 14640555
TI  - Carbonic anhydrase inhibitors: inhibition of transmembrane, tumor-associated
      isozyme IX, and cytosolic isozymes I and II with aliphatic sulfamates.
AB  - A series of aliphatic sulfamates and related derivatives incorporating
      cyclic/polycyclic (steroidal) moieties in their molecules has been synthesized
      and assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA) and, more
      precisely, of the cytosolic isozymes CA I and II and the transmembrane, tumor
      associated isozyme CA IX. The most potent CA I inhibitor was n-tetradecyl
      sulfamate and some (substituted)benzyl/phenethyl sulfamates (inhibition constants
      in the low micromolar range). Against CA II, low nanomolar inhibitors (0.7-3.4
      nM) were n-decyl sulfamate and the (substituted)benzyl/phenethyl derivatives
      mentioned above. Effective CA II inhibition was also observed for the
      hydroxy/keto derivatives of dehydroepiandrosterone sulfamate. Efficient CA IX
      inhibitory properties, with inhibition constants in the range of 9-23 nM, were
      observed for the aliphatic sulfamates C(10)-C(16) (with the most potent inhibitor
      being the n-dodecyl derivative) and the (substituted)benzyl/phenethyl sulfamates.
      The inhibition profile of the three investigated isozymes with this type of
      compound was rather different, allowing us to hope that the preparation of CA IX
      selective inhibitors is possible (selectivity ratios toward hCA IX versus hCA II
      in the range of 5-63 has been observed for some of these compounds, whereas for
      the clinically used sulfonamides this parameter is in the range of 0.23-0.51).
      These data are critical for the design of novel antitumor therapies, mainly for
      hypoxic tumors that overexpress CA IX, which are nonresponsive to radiation or
      chemotherapy.

PMID- 14640556
TI  - Polyamine-iron chelator conjugate.
AB  - The current study demonstrates unequivocally that polyamines can serve as vectors
      for the intracellular delivery of the bidentate chelator 1,2-dimethyl-3
      hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone conjugate 1-(12-amino
      4,9-diazadodecyl)-2-methyl-3-hydroxy-4(1H)-pyridinone is assembled from spermine
      and 3-O-benzylmaltol. The conjugate is shown to form a 3:1 complex with Fe(III)
      and to be taken up by the polyamine transporter 1900-fold against a concentration
      gradient. The K(i) of the conjugate is 3.7 microM vs spermidine for the polyamine
      transporter. The conjugate is also at least 230 times more active in suppressing
      the growth of L1210 murine leukemia cells than is the parent ligand, decreases
      the activities of the polyamine biosynthetic enzymes ornithine decarboxylase and
      S-adenosylmethionine decarboxylase, and upregulates spermidine-spermine N (1)
      acetyltransferase. However, the effect on native polyamine pools is a moderate
      one. These findings are in keeping with the idea that polyamines can also serve
      as efficient vectors for the intracellular delivery of other iron chelators.

PMID- 14640557
TI  - Synthesis and structure-activity relationship of novel, highly potent metharyl
      and methcycloalkyl cyclooxygenase-2 (COX-2) selective inhibitors.
AB  - A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and
      evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in
      human whole blood (HWB). In the present study, structure-activity relationships
      (SAR) in the metharyl analogues were investigated. The spacer group and
      substitutions in the spacer group were found to be quite important for potent COX
      2 inhibition. Compounds in which a methylene group (8a-c), carbonyl group (12a
      c), or methylidene group (7a-c) connected cycloalkyl groups to the central benzo
      1,3-dioxolane template were found to be potent and selective COX-2 inhibitors.
      Aryl-substituted compounds linked to the central ring by either a methylene or a
      carbonyl spacer resulted in potent, highly selective COX-2 inhibitors. In this
      series of substituted-(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-1
      (methylsulfonyl)benzene compounds, SAR studies demonstrated that substitution at
      the 3-position of the aryl group optimized COX-2 selectivity and potency, whereas
      substitution at the 4-position attenuated COX-2 inhibition. Mono- or difluoro
      substitution at meta position(s), as in 22c and 22h, was advantageous for both in
      vitro COX-2 potency and selectivity (e.g., COX-2 IC(50) for 22c = 1 microM and
      COX-1 IC(50) for 22c = 20 microM in HWB assay). Several novel compounds in the
      (2H-benzo[3,4-d]1,3-dioxolan-5-yl))-1-(methylsulfonyl)benzene series, as shown in
      structures 7c, 8a, 12a, 21c, 22c, 22e, and 22h, selectively inhibited COX-2
      activity by 40-50% at a test concentration of 1 microM in an in vitro HWB assay.

PMID- 14640558
TI  - Guanidino N-substituted and N,N-disubstituted derivatives of the kappa-opioid
      antagonist GNTI.
AB  - Derivatives of the highly selective kappa-opioid receptor antagonist GNTI (2a)
      have been prepared. Binding and functional studies conducted on cloned human
      opioid receptors expressed in Chinese hamster ovarian (CHO) cells suggested that
      adding a benzyl or a substituted benzyl group to the guanidino moiety led, in
      general, to a retention of high kappa-affinity and antagonist potency.
      Disubstitution of the guanidino moiety led to reduced kappa-selectivity.

PMID- 14640559
TI  - Syntheses and binding studies of new [(aryl)(aryloxy)methyl]piperidine
      derivatives and related compounds as potential antidepressant drugs with high
      affinity for serotonin (5-HT) and norepinephrine (NE) transporters.
AB  - In a wide search program toward new, efficient, and fast-acting antidepressant
      drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl
      moiety linked directly or through a methylene chain to different substituted and
      unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or
      cyclopentane). These compounds have been evaluated for their affinities for
      serotonin (5-HT) transporter (SERT) and 5-HT(1A) and 5-HT(2A) receptors. Racemic
      mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher
      affinity values for SERT than fluoxetine and resulted in lack of affinity for 5
      HT(1A) and 5-HT(2A) receptors. Some of these racemic mixtures were resolved to
      their enantiomers and tested for binding to norepinephrine (NE) transporter
      (NET), dopamine (DA) transporter (DAT), and alpha(2) receptor. Several of these
      enantiomers [(-)-15b, (-)-15j, (-)-15t, (+)-15u] displayed a dual binding profile
      with affinities for SERT and NET with K(i) < 25 nM and a NET/SERT ratio <10.
      Compound (-)-15j (coded as F-98214-TA for development studies) showed a dual
      binding profile with very high affinity values for SERT and NET (K(i) = 1.9 and
      13.5 nM, respectively), and further pharmacological characterization is in
      progress for its evaluation as a antidepressant.

PMID- 14640560
TI  - Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with
      nitroreductase-mediated gene-directed enzyme prodrug therapy.
AB  - A variety of nitroheterocyclic carbamate prodrugs of phenylenediamine mustard and
      5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H
      benz[e]indoline (amino-seco-CBI-TMI), covering a wide range of reduction
      potential, were prepared and evaluated for use in gene-directed enzyme prodrug
      therapy (GDEPT) using a two-electron nitroreductase (NTR) from Escherichia coli
      B. The carbamate prodrugs and corresponding amine effectors were tested in a cell
      line panel comprising parental and NTR-transfected human (SKOV3/SKOV3-NTR(neo),
      WiDr/WiDr-NTR(neo)), Chinese hamster (V79(puro)/V79-NTR(puro)), and murine
      (EMT6/EMT6-NTR(puro)) cell line pairs and were compared with the established NTR
      substrates CB1954 (an aziridinyl dinitrobenzamide) and the analogous
      dibromomustard. The 1-methyl-2-nitroimidazol-5-ylmethyl carbamate of
      phenylenediamine mustard was metabolized rapidly by EMT6-NTR(neo) but not EMT6
      cells, demonstrating that it is an efficient substrates for NTR. Despite this,
      the carbamates of phenylenediamine mustards show relatively low differential
      cytotoxicity for NTR+ve cells in IC(50) assays, apparently because they retain
      sufficient alkylating reactivity that most of the prodrug reacts with
      nucleophiles during the drug exposure period. In contrast, the corresponding
      amino-seco-CBI-TMI prodrugs were less efficient NTR substrates but had greater
      chemical stability, were more potent, and showed substantial NTR-ve/NTR+ve ratios
      in the cell line panel, with ratios of 15-100-fold for the 1-methyl-2-nitro-1H
      imidazol-5-ylmethyl and 1-methyl-5-nitro-1H-imidazol-2-ylmethyl carbamates of
      amino-seco-CBI-TMI. The activity of these two prodrugs was evaluated against NTR
      expressing EMT6 tumors comprising ca. 10% NTR+ve cells. Small but not
      statistically significant killing of NTR+ve cells was observed, with no effect
      against NTR-ve target cells. The lack of activity against NTR+ve cells in tumors,
      despite potent and selective activity in culture, indicates that pharmacokinetic
      optimization will be required if in vivo efficacy against solid tumors is to be
      achieved with this new class of NTR prodrugs.

PMID- 14640562
TI  - Coupling proton transfer reaction-mass spectrometry with linear discriminant
      analysis: a case study.
AB  - Proton transfer reaction-mass spectrometry (PTR-MS) measurements on single intact
      strawberry fruits were combined with an appropriate data analysis based on
      compression of spectrometric data followed by class modeling. In a first
      experiment 8 of 9 different strawberry varieties measured on the third to fourth
      day after harvest could be successfully distinguished by linear discriminant
      analysis (LDA) on PTR-MS spectra compressed by discriminant partial least squares
      (dPLS). In a second experiment two varieties were investigated as to whether
      different growing conditions (open field, tunnel), location, and/or harvesting
      time can affect the proposed classification method. Internal cross-validation
      gives 27 successes of 28 tests for the 9 varieties experiment and 100% for the 2
      clones experiment (30 samples). For one clone, present in both experiments, the
      models developed for one experiment were successfully tested with the homogeneous
      independent data of the other with success rates of 100% (3 of 3) and 93% (14 of
      15), respectively. This is an indication that the proposed combination of PTR-MS
      with discriminant analysis and class modeling provides a new and valuable tool
      for product classification in agroindustrial applications.

PMID- 14640561
TI  - Synthesis of a prodrug designed to release multiple inhibitors of the epidermal
      growth factor receptor tyrosine kinase and an alkylating agent: a novel tumor
      targeting concept.
AB  - The synthesis of a novel acetoxymethyltriazene designed to be a prodrug of
      multiple inhibitors of the epidermal growth factor receptor (EGFR) and a
      methyldiazonium species is described. Studies with each of the expected
      metabolites demonstrated significant EGFR tyrosine kinase inhibitory activities
      and the released methyldiazonium was trapped with p-nitrobenzylpyridine. Their
      ability to damage genomic DNA in whole cells was demonstrated by using the single
      cell microelectrophoresis (comet) assay. The results suggest that this approach
      may well represent a novel drug combination strategy involving single molecules
      masking multiple bioactive agents.

PMID- 14640563
TI  - Analysis of reducing carbohydrates by reductive tryptamine derivatization prior
      to micellar electrokinetic capillary chromatography.
AB  - A micellar electrokinetic capillary chromatography method for determination of
      low molecular weight carbohydrates (dp 1-2) with an unbound carbonyl group as in
      aldoses or other reducing carbohydrates has been developed. Reductive amination
      of aldoses on the carbonyl group using tryptamine introduced a chromophor system
      to the carbohydrates enabling their sensitive UV detection at 220 nm and
      identification based on the indole group using diode array detection. Twelve
      carbohydrates including pentoses (d-ribose, l-arabinose, and d-xylose), hexoses
      (d-glucose, d-mannose, and d-galactose), deoxy sugars (l-rhamnose and l-fucose),
      uronic acids (d-glucuronic acid and d-galacturonic acid), and disaccharides
      (cellobiose and melibiose) are included in the study, using d-thyminose (2-deoxy
      d-ribose) as the internal standard. Detection of all 12 carbohydrates is
      performed within 30 min. Linearity with correlation coefficients from 0.9864 to
      0.9992 was found in the concentration range of 25-2500 micromol/L for all
      carbohydrates; the relative standard deviation on the migration times was between
      0.27 and 0.80 min, and limits of quantification and limits of determination were
      in the picomole range.

PMID- 14640564
TI  - Contribution of individual polyphenolics to total antioxidant capacity of plums.
AB  - To study the effect of polyphenolics on antioxidant capacities of plums, the
      amounts of total phenolics, total flavonoids and individual phenolic compounds,
      and vitamin C equivalent antioxidant capacity (VCEAC) of eleven plum cultivars
      was determined. There was a good linear relationship between the amount of total
      phenolics and total antioxidant capacity (r2 = 0.9887). The amount of total
      flavonoids and total antioxidant capacity also showed a good correlation (r2 =
      0.9653). Although the summation of individual antioxidant capacity was lower than
      the total antioxidant capacity of plum samples, there was a positive correlation
      (r2 = 0.9299) of total antioxidant capacity of plum samples with the sum of the
      VCEACs calculated from individual phenolics. Chlorogenic acids and glycosides of
      cyanidin, peonidin, and quercetin were major phenolics among eleven plum
      cultivars. The antioxidant capacity of chlorogenic acids and anthocyanins showed
      higher correlation (r2) of 0.7751 and 0.6616 to total VCEAC, respectively, than
      that of quercetin glycosides (r2 = 0.0279). Chlorogenic acids were a major source
      of antioxidant activity in plums, and the consumption of one serving (100 g) of
      plums can provide antioxidants equivalent to 144.4-889.6 mg of vitamin C.

PMID- 14640565
TI  - A simple extraction and chromatographic system for the simultaneous analysis of
      anthocyanins and stilbenes of Vitis species.
AB  - A separation system has been developed to permit the simultaneous analysis of
      major anthocyanins and stilbenes from berries of Vitis species in <1 h. The
      system makes use of separation by HPLC and detection by UV-visible absorption and
      fluorescence, for anthocyanins and stilbenes, respectively, with the two
      detection systems linked in series. Monitoring the absorption at 520 nm permits
      ready identification and quantification of major anthocyanins. Chromatograms
      derived from fluorescence (330 nm excitation/374 nm emission) produce less clear
      data for the piceids and resveratrols, which are present in much lower amounts;
      peaks for these compounds can be verified by means of external or internal
      standards.

PMID- 14640566
TI  - Analytical method for the determination of atrazine and its dealkylated
      chlorotriazine metabolites in water using SPE sample preparation and GC-MSD
      analysis.
AB  - A method is reported for the determination of atrazine and its dealkylated
      chlorotriazine metabolites in ground, surface, and deionized water. Water samples
      are adjusted to pH 3-4 prior to loading onto two SPE cartridges in series: C-18
      and C-18/cation exchange mixed-mode polymeric phases. The analytes are eluted
      from each of the two cartridges separately, and the pooled and concentrated
      fraction is analyzed using gas chromatography-mass selective detection in the
      selected ion monitoring mode. The lower limit of method validation is 0.10
      micrograms/L (ppb) for 2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine
      (atrazine), 2-amino-4-chloro-6-(isopropylamino)-s-triazine (G-30033,
      deethylatrazine), 2-amino-4-chloro-6-(ethylamino)-s-triazine (G-28279,
      deisopropylatrazine), and 2,4-diamino-6-chloro-s-triazine (G-28273,
      didealkyatrazine). The overall mean procedural recoveries (and standard
      deviations) are 96 (6.9), 96 (5.5), 95 (6.8), and 100% (10%) for atrazine, G
      30033, G-28279, and G-28273, respectively (n = 49). The method validation study
      was conducted under U.S. EPA FIFRA Good Laboratory Practice Guidelines 40 CFR
      160. The reported procedure accounts for residues of G-28273 in water.

PMID- 14640567
TI  - Simultaneous quantitative analysis of maillard reaction precursors and products
      by high-performance anion exchange chromatography.
AB  - A new analytical setup allowing the simultaneous analysis of precursors and
      products of the Maillard reaction is described. It is based on high-performance
      anion exchange chromatography with electrochemical (ECD) and diode array
      detectors (DAD) coupled in series. Chromatography and detection were optimized to
      permit simultaneous monitoring of compounds relevant to the Maillard reaction,
      such as the sugar, the amino acid, and the corresponding Amadori compound as well
      as the cyclic intermediates 5-(hydroxymethyl)-2-furaldehyde, maltol, and 2,3
      dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one. Separation was achieved on a
      CarboPac PA-1 column using a gradient of sodium acetate in aqueous sodium
      hydroxide. The Amadori compound, glucose, and glycine were monitored by an ECD
      operating in the integrated amperometry mode. The number of analyzed compounds
      was further increased by coupling the ECD with a DAD for the analysis of
      ultraviolet-active constituents. This method was successfully applied to model
      Maillard reaction mixtures based on glucose and glycine.

PMID- 14640568
TI  - Application of tristimulus colorimetry to estimate the carotenoids content in
      ultrafrozen orange juices.
AB  - Tristimulus Colorimetry was applied to characterize the color of Valencia late
      orange juices. Color measurements were made against white background and black
      background. The profile of the main carotenoids related to the color of the
      juices was determined by HPLC. Significant correlations (p < 0.05) between b*,
      Cab* and h(ab) and the content of beta-cryptoxanthin, lutein + zeaxanthin and
      beta-carotene were found. The correlations between the color parameters L*, a*,
      b*, Cab* and h(ab) and the carotenoids content were also explored by partial
      least squares. The results obtained have shown that it is possible to obtain
      equations, by means of multiple regression models, which allow the determination
      of the individual carotenoid levels from the CIELAB color parameters, with R2
      values always over 0.9. In this sense, equations have been proposed to calculate
      the retinol equivalents (1 RE = 1 microgram retinol = 12 micrograms beta-carotene
      = 24 micrograms alpha-carotene = 24 micrograms beta-cryptoxanthin) of the orange
      juice analyzed as a function of the color parameters calculated from measurement
      made against white and black backgrounds. The average RE per liter of juice
      obtained by HPLC was 51.07 +/- 18.89, whereas employing these equations, average
      RE values obtained were 51.16 +/- 1.36 and 51.21 +/- 1.70 for white background
      and black background, respectively.

PMID- 14640569
TI  - Antifeedant effects of the limonoids from Entandrophragma candolei (Meliaceae) on
      the gram pod borer, Helicoverpa armigera (Lepidoptera: Noctuidae).
AB  - The biological activity of the limonoids prieurianin and epoxyprieurianin
      isolated from Entandrophragma candolei (Harms) (Meliaceae) and their respective
      acetates was assessed using the gram pod borer, Helicoverpa armigera (Hubner)
      (Lepidoptera: Noctuidae). The compounds exhibited strong antifeedant activity in
      a diet choice bioassay with epoxyprieurianin acetate being most effective with
      48.3 ppm deterring feeding by 50% (DI50) and prieurianin the least effective
      (DI50 = 91.4 ppm). The effect on growth of larvae was concomitant with the
      reduced feeding by neonate and third instar larvae. In nutritional assays, all
      the compounds reduced growth and consumption when fed to larvae without any
      effect on efficiency of conversion of ingested food (ECI), suggesting antifeedant
      activity alone. No toxicity was observed nor was there any significant affect on
      nutritional indices following topical application, further suggesting that
      prieurianin-type limonoids act specifically as feeding deterrents.

PMID- 14640570
TI  - Baicalin induces differential expression of cytochrome C oxidase in human lung
      H441 cell.
AB  - In a previous study, we evaluated the effect of baicalin on the expression of SP
      A (surfactant protein A), which was developmentally regulated in an alveolar type
      II cell, H441. SP-A is encoded by two similar genes, SP-A1 and SP-A2, in humans.
      The maximal induction of SP-A1 gene of H441 occurred at treating 150 nM of
      baicalin for 48 h. In the present study, cDNA subtraction analysis is performed
      to examine the differential expression in H441 cell upon baicalin treatment with
      a view to investigating the regulatory mechanism. The mRNA of H441 cell incubated
      with 150 nM baicalin for 48 h was compared to that of blank control. Two PCR
      products were obtained through subtractive cDNA amplification. A product encoding
      cytochrome c oxidase was demonstrated to be a differential signal by RT-PCR
      analysis, and the other was a false positive. The induction of cytochrome c
      oxidase might increase ATP level in cell, and consequently elevates cAMP, which
      upregulates surfactant synthesis and secretion.

PMID- 14640571
TI  - Inhibition of rat mammary tumorigenesis by concord grape juice constituents.
AB  - The effects of Concord grape juice constituents on the promotion of chemically
      induced rat mammary tumor development and on the proliferation of a rat mammary
      adenocarcinoma cell line were studied. Isocaloric grape juice formulations
      provided in the drinking fluid of rats at concentrations of 489 and 651 mg of
      phenolics/dL of fluid significantly inhibited mammary adenocarcinoma multiplicity
      compared to controls. Final tumor mass also was significantly decreased for
      animals provided these two grape juice concentrations compared to controls. In
      addition, DNA synthesis of the rat mammary adenocarcinoma RBA cell line was
      significantly inhibited in a dose-dependent manner for cells treated with a grape
      extract, with an IC50 dose of approximately 14 micrograms of phenolics/mL. This
      inhibition of DNA synthesis was not accompanied by changes in 8-oxodeoxyguanosine
      formation or by substantial cell cycle arrest. These studies thus indicate that
      Concord grape juice constituents can inhibit the promotion stage of 7,12
      dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis, in part by
      suppressing cell proliferation.

PMID- 14640572
TI  - Buckwheat concentrate reduces serum glucose in streptozotocin-diabetic rats.
AB  - The antihyperglycemic effects of chemically synthesized d-chiro-inositol (d-CI),
      a component of an insulin mediator, have been demonstrated in rats. Buckwheat
      contains relatively high levels of d-CI: thus, it has been proposed as a source
      of d-CI for reducing serum glucose concentrations in diabetics. The present study
      evaluates the effects of a buckwheat concentrate, containing d-CI, on
      hyperglycemia and glucose tolerance in streptozotocin (STZ) rats. In fed STZ
      rats, both doses of the buckwheat concentrate (containing 10 and 20 mg of d-CI/kg
      of body weight) were effective for lowering serum glucose concentrations by 12
      19% at 90 and 120 min after administration. Findings from this study demonstrate
      that a buckwheat concentrate is an effective source of d-CI for lowering serum
      glucose concentrations in rats and therefore may be useful in the treatment of
      diabetes.

PMID- 14640573
TI  - Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than
      teas and red wine.
AB  - Black tea, green tea, red wine, and cocoa are high in phenolic phytochemicals,
      among which theaflavin, epigallocatechin gallate, resveratrol, and procyanidin,
      respectively, have been extensively investigated due to their possible role as
      chemopreventive agents based on their antioxidant capacities. The present study
      compared the phenolic and flavonoid contents and total antioxidant capacities of
      cocoa, black tea, green tea, and red wine. Cocoa contained much higher levels of
      total phenolics (611 mg of gallic acid equivalents, GAE) and flavonoids (564 mg
      of epicatechin equivalents, ECE) per serving than black tea (124 mg of GAE and 34
      mg of ECE, respectively), green tea (165 mg of GAE and 47 mg of ECE), and red
      wine (340 mg of GAE and 163 mg of ECE). Total antioxidant activities were
      measured using the 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS)
      and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays and are
      expressed as vitamin C equivalent antioxidant capacities (VCEACs). Cocoa
      exhibited the highest antioxidant activity among the samples in ABTS and DPPH
      assays, with VCEACs of 1128 and 836 mg/serving, respectively. The relative total
      antioxidant capacities of the samples in both assays were as follows in
      decreasing order: cocoa > red wine > green tea > black tea. The total antioxidant
      capacities from ABTS and DPPH assays were highly correlated with phenolic content
      (r2 = 0.981 and 0.967, respectively) and flavonoid content (r2 = 0.949 and
      0.915). These results suggest that cocoa is more beneficial to health than teas
      and red wine in terms of its higher antioxidant capacity.

PMID- 14640574
TI  - Tea polyphenols inhibit the transport of dietary phenolic acids mediated by the
      monocarboxylic acid transporter (MCT) in intestinal Caco-2 cell monolayers.
AB  - It was previously reported that a fluorescent marker dye, fluorescein, is
      transported via the monocarboxylic acid transporter (MCT). Fluorescein transport
      was competitively inhibited by MCT substrates such as ferulic and salicylic
      acids. Tea polyphenols, in particular, epigallocatechin gallate (EGCg) and
      epicatechin gallate (ECg), inhibited the transport of fluorescein. Tea
      polyphenols also inhibited the transport of salicylic and ferulic acids,
      suggesting tea polyphenols might be substrates of MCT. However, the
      transepithelial flux of tea polyphenols was much lower than that of the MCT
      substrates and was inversely correlated with the paracellular permeability of
      Caco-2 cell monolayers. These findings suggest that tea polyphenols are not
      substrates but inhibitors of MCT. Furthermore, the transepithelial transport of
      these polyphenols is mainly via paracellular diffusion. However, directional
      transport of ECg and EGCg from the basolateral to the apical side was observed,
      indicating that the behavior of tea polyphenols in the intestinal epithelium is
      complex.

PMID- 14640575
TI  - Heat-epimerized tea catechins rich in gallocatechin gallate and catechin gallate
      are more effective to inhibit cholesterol absorption than tea catechins rich in
      epigallocatechin gallate and epicatechin gallate.
AB  - It has been known that tea catechins, (-)-epicatechin (1), (-)-epigallocatechin
      (2), (-)-epicatechin gallate (3), and (-)-epigallocatechin gallate (4) are
      epimerized to(-)-catechin (5), (-)-gallocatechin (6), (-)-catechin gallate (7),
      and (-)-gallocatechin gallate (8), respectively, during retort pasteurization. We
      previously reported that tea catechins, mainly composed of 3 and 4, effectively
      inhibit cholesterol absorption in rats. In this study, the effect of heat
      epimerized catechins on cholesterol absorption was compared with tea catechins.
      Both tea catechins and heat-epimerized catechins lowered lymphatic recovery of
      cholesterol in rats cannulated in the thoracic duct and epimerized catechins were
      more effective than tea catechins. The effect of purified catechins on micellar
      solubility of cholesterol was examined in an in vitro study. The addition of
      gallate esters of catechins reduced micellar solubility of cholesterol by
      precipitating cholesterol from bile salt micelles. Compounds 7 and 8 were more
      effective to precipitate cholesterol than 3 and 4, respectively. These
      observations strongly suggest that heat-epimerized catechins may be more
      hypocholesterolemic than tea catechins.

PMID- 14640576
TI  - Methanolic extract of Verbascum macrurum as a source of natural preservatives
      against oxidative rancidity.
AB  - The antioxidant properties of various fractions of a methanolic extract obtained
      from the aerial parts of Verbascum macrurum have been determined by monitoring
      their capacity to scavenge the stable free-radical DPPH. They were also evaluated
      as natural preservatives against oxidative rancidity using the accelerated
      Rancimat method. Their activities expressed as protection factor (PF(r))
      indicated that the fractions rich with phenylpropanoid glycosides were more
      potent compared to alpha-tocopherol and of the same magnitude as BHT, which were
      used as reference standards. Ten natural compounds were identified as components
      of this methanolic extract and were isolated by medium-pressure liquid
      chromatography (MPLC). Assessment of their antioxidant activities established
      that acteoside, a polyhydroxylated phenylpropanoid glycoside derivative, is the
      most potent free radical scavenger and showed the highest protection factor
      (PF(r)) against sunflower-oil-induced oxidative rancidity. Its activity is
      comparable to the synthetic antioxidant BHT and clearly superior to natural alpha
      tocopherol. This compound therefore represents a very interesting candidate for
      use in food preservation as natural protecting agent against oxidative rancidity.

PMID- 14640577
TI  - Identification of six phenylpropanoids from garlic skin as major antioxidants.
AB  - The extract of garlic skins (peels) showed strong antioxidant activity, and some
      responsible constituents were isolated and identified. Garlic (Allium sativum L.)
      has been used as an herbal medicine, but there is no report on the health
      benefits of the skin or peel. In this study, the 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical scavenging activity of garlic skin extract was evaluated. Using
      chromatographic techniques, the active constituents were isolated and
      subsequently identified. Analyses by high-performance liquid chromatography
      coupled with a photodiode array detector (HPLC-PDA) suggested that these
      compounds were phenylpropanoids, which had a characteristic absorbance at 300-320
      nm. Liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic
      resonance analyses allowed the chemical structures of the isolated constituents
      to be postulated. The proposed compounds were subsequently synthesized and
      compared with the constituents in the extract using HPLC-PDA and LC-MS. N-trans
      Coumaroyloctopamine, N-trans-feruloyloctopamine, guaiacylglycerol-beta-ferulic
      acid ether, and guaiacylglycerol-beta-caffeic acid ether were identified as were
      trans-coumaric acid and trans-ferulic acid. Also, the antioxidant activities of
      these compounds were determined.

PMID- 14640578
TI  - Cleavage products of lycopene produced by in vitro oxidations: characterization
      and mechanisms of formation.
AB  - The aim of this study was to produce in vitro oxidation products of lycopene,
      which could be possible in vivo metabolites. An oxidation of lycopene with
      potassium permanganate gave a range of lycopene degradation compounds resulting
      from the oxidative cleavage of one or two carbon-carbon double bonds. Eleven apo
      lycopenals/ones and six apo-carotendials were obtained and tentatively
      characterized by HPLC-DAD-MS. Apo-11-lycopenal and apo-8,6'-carotendial were
      isolated and characterized by (1)H NMR for the first time. Lycopene was submitted
      to an oxidation by atmospheric oxygen catalyzed by a metalloporphyrin, a model
      system of the active center of cytochrome P450 enzymes. (Z)-Isomers, monoxides,
      and cleavage compounds of (E)-lycopene were formed. We propose a mechanism of
      oxidation of lycopene by this system.

PMID- 14640579
TI  - Direct sequencing method for species identification of canned sardine and sardine
      type products.
AB  - A direct sequencing method based on a 103 bp diagnostic sequence derived from a
      species-specific mitochondrial DNA cytochrome b sequence of 150 bp obtained by
      Polymerase Chain Reaction was tested for the identification of 47 commercial
      canned sardine and sardine-type products from various countries. Multiple
      alignment of 14 analyzed reference samples belonging to Clupeomorpha species was
      performed versus the canned samples. Low intraspecific variability was observed
      for canned sardine (</=0.03), whereas mean interspecific variability was 0.23. A
      phylogenetic tree was constructed, and the calculated bootstrap values (BP, 88
      99%) were used as indicators of the correct assignment of unknown canned samples
      to reference species. According to this methodology, the 26 commercial canned
      sardines analyzed were grouped in the same clade as the Sardina pilchardus
      reference and identified unequivocally. These assignments were confirmed by the
      high BP value of 99%.

PMID- 14640580
TI  - Methanolic extract of adlay seed suppresses COX-2 expression of human lung cancer
      cells via inhibition of gene transcription.
AB  - Previous results demonstrated that the methanolic extract of adlay seed exerted
      an antiproliferative effect on human lung cancer cells in vitro and in vivo and
      might prevent tobacco carcinogen-induced lung tumorigenesis. In this study, the
      methanolic extract of adlay seed was tested for its regulation of COX-2
      expression of human lung cancer cells. Western blot analysis showed that the
      methanolic extract of adlay seed inhibited basal and TPA-induced COX-2 expression
      in a dose-dependent fashion, whereas COX-1 expression was not affected. By using
      a promoter activity assay, it was found that the methanolic extract inhibited
      basal and TPA-stimulated COX-2 expression at the transcription level. The effect
      of the methanolic extract on COX-2 expression in vivo was then investigated. The
      data demonstrated that treatment of the methanolic extract reduced the PGE(2)
      level in serum and inhibited COX-2 expression of tumor tissues in nude mice.
      Taken together, these results suggest that inhibition of COX-2 is one of the
      mechanisms by which the methanolic extract of adlay seed inhibits cancer growth
      and prevents lung tumorigenesis.

PMID- 14640581
TI  - Impact of xylanases with different substrate selectivity on gluten-starch
      separation of wheat flour.
AB  - The influence on wheat flour gluten-starch separation of a xylanase from
      Aspergillus aculeatus (XAA) with hydrolysis selectivity toward water extractable
      arabinoxylan (WE-AX) and that is not inhibited by wheat flour xylanase inhibitors
      was compared to that of a xylanase from Bacillus subtilis (XBS) with hydrolysis
      selectivity toward water unextractable arabinoxylan (WU-AX) and that is inhibited
      by such inhibitors. XAA improved gluten agglomeration through degradation of WE
      AX and concomitant reduction in viscosity, which in the laboratory scale batter
      procedure with a set of vibrating sieves (400, 250, and 125 microm), increased
      protein recoveries on the 400 microm sieve. In contrast, XBS had a negative
      effect as it decreased gluten protein recovery on this sieve, probably as a
      result of the viscosity increase that accompanied WU-AX solubilization. Hence, it
      was active even if most likely a considerable part of its activity was prevented
      by xylanase inhibitors. A combination of XAA and XBS at a low dosage yielded a
      distribution of gluten proteins on the different sieves comparable to that of the
      control. At a high combined dosage, the gluten agglomeration was better than that
      with XAA alone, indicating that both WE-AX and WU-AX have a negative impact on
      gluten agglomeration. Finally, experiments with endoxylanase addition at
      different moments during the separation process suggest that the status of the
      arabinoxylan population during dough mixing is far less critical for its impact
      on gluten agglomeration than that during the batter phase.

PMID- 14640582
TI  - Effect of extraction method on the concentrations of selected bioactive compounds
      in mandarin juice.
AB  - A mandarin-type citrus fruit, ponkan (Citrus reticulata), was processed by in
      line, chopper pulper, and hand-press extractions to investigate the effect of
      extraction method on the concentrations of bioactive compounds in processed
      juice. Concentrations of polymethoxylated flavones (tangeretin, nobiletin, and
      sinensetin) and beta-cryptoxanthin in juice, and inhibitory activities against
      arachidonate cyclooxygenase and lipoxygenases of the juice extract were analyzed.
      The juice processed by hand-press extraction contained the largest amounts of
      nobiletin (3.56 mg/100 mL), tangeretin (4.10 mg/100 mL), and sinensetin (0.13
      mg/100 mL). Concentrations of beta-cryptoxanthin were 0.66, 0.59, 0.55, and 0.50
      mg/100 mL in chopper pulper, in-line (5/64 in.), in-line (8/64 in.) and hand
      press juices, respectively. Both extracts of in-line juices showed greater
      inhibitory activity toward platelet 12-lipoxygenase than the others. The
      inhibitory effect of hand-press juice extract on platelet cyclooxygenase activity
      was remarkable among juice extracts. All juice extracts effectively inhibited
      polymorphonuclear 5-lipoxygenase activity at nearly the same rate.

PMID- 14640583
TI  - Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from
      three commercial suppliers.
AB  - The characterization of herbal materials is a significant challenge to analytical
      chemists. Goldenseal (Hydrastis canadensis L.), which has been chosen for
      toxicity evaluation by NIEHS, is among the top 15 herbal supplements currently on
      the market and contains a complex mixture of indigenous components ranging from
      carbohydrates and amino acids to isoquinoline alkaloids. One key component of
      herbal supplement production is botanical authentication, which is also
      recommended prior to initiation of efficacy or toxicological studies. To evaluate
      material available to consumers, goldenseal root powder was obtained from three
      commercial suppliers and a strategy was developed for characterization and
      comparison that included Soxhlet extraction, HPLC, GC-MS, and LC-MS analyses.
      HPLC was used to determine the weight percentages of the goldenseal alkaloids
      berberine, hydrastine, and canadine in the various extract residues. Palmatine,
      an isoquinoline alkaloid native to Coptis spp. and other common goldenseal
      adulterants, was also quantitated using HPLC. GC-MS was used to identify non
      alkaloid constituents in goldenseal root powder, whereas LC-MS was used to
      identify alkaloid components. After review of the characterization data, it was
      determined that alkaloid content was the best biomarker for goldenseal. A 20-min
      ambient extraction method for the determination of alkaloid content was also
      developed and used to analyze the commercial material. All three lots of
      purchased material contained goldenseal alkaloids hydrastinine, berberastine,
      tetrahydroberberastine, canadaline, berberine, hydrastine, and canadine. Material
      from a single supplier also contained palmatine, coptisine, and jatrorrhizine,
      thus indicating that the material was not pure goldenseal. Comparative data for
      three commercial sources of goldenseal root powder are presented.

PMID- 14640584
TI  - Persistence of simazine and terbuthylazine in a semiarid soil after organic
      amendment with urban sewage sludge.
AB  - The persistence of two herbicides, simazine and terbuthylazine, and appearance of
      their principal dealkylated chloro-s-triazine metabolites have been studied in
      agricultural soil after the addition of urban sewage sludge as organic amendment.
      Both herbicides and metabolites were monitored during long-term laboratory
      incubation (140 days) and analyzed by gas chromatography with a nitrogen
      phosphorus detector (GC-NPD). Residues were confirmed by gas chromatography with
      a mass selective detector (GC-MSD). A sonication microextraction method was used
      to extract the compounds. The organic amendments used were urban sewage sludge
      and the humic fraction of this sludge, to increase the organic matter content of
      the soil from 1% to 2%. For both compounds, simazine and terbuthylazine, the
      degradation began earlier in the amended soils. Simazine showed a higher
      dissipation rate than terbuthylazine, the percentage of the former at the end of
      the experiment being lower than 2% in all cases, while for terbuthylazine the
      corresponding percentage ranged from 5% to 46%. Organic amendment, mainly its
      humic fraction, caused a certain stabilization of terbuthylazine in the soil, but
      did not greatly influence the residual amount of simazine at the end of the
      experiment. The periodic aeration of the soil caused a greater degradation in the
      case of terbuthylazine. Only mono-deethylsimazine and deethylterbuthylazine were
      isolated from the soil during the time the experiment lasted, while the di
      deethylated metabolite of simazine was not found.

PMID- 14640585
TI  - Formation of nitric oxide during tobacco oxidation.
AB  - The sources of NO during biomass oxidation, and in particular tobacco oxidation,
      have been disputed. Literature results range from decomposition of nitrate to the
      oxidation of atmospheric nitrogen. To rectify these discrepancies, this study
      focuses on the sources of nitric oxide (NO) during the oxidation of tobacco
      samples. When Burley tobacco was heated in a partially oxidized atmosphere, NO
      was produced at two distinct temperature ranges, namely 275-375 degrees C (the
      low-temperature range) and 425-525 degrees C (the high-temperature range). The
      formation of NO at the low-temperature range with Burley tobacco was found to be
      unaffected by oxygen, while the formation of NO at the high-temperature range
      required an oxygen atmosphere. With Bright and Oriental tobacco, NO was produced
      only within the higher-temperature range. To understand the formation processes
      and the sources of NO formation within these two temperature ranges, several
      endogenous nitrogenous tobacco compounds were examined. These were mixed with non
      nitrogenous biomass model materials, namely cellulose, pectin, xylan, or lignin,
      which also occur naturally in tobacco, and the mixtures were heated in a flow
      tube reactor under a partially oxidative atmosphere. A commercial gas analyzer
      was used to monitor the formation of NO during heating. Nitrate ion was
      determined to be the source of NO formation in the range of 275-375 degrees C.
      This ion was decomposed in a carbonaceous surrounding to produce NO. For NO
      formation at the higher temperature range, amino acids and proteins were shown to
      be the sources. The interaction between nitrogenous organic compounds (amino
      acids and proteins) and pectin first produced a nitrogen-containing char at a
      temperature below 350 degrees C. Oxidation of this char at the higher
      temperatures produced NO.

PMID- 14640586
TI  - Investigation of methylmercury and total mercury contamination in mollusk samples
      collected from coastal sites along the Chinese Bohai Sea.
AB  - This paper presents the investigation results of methylmercury and total mercury
      in gastropod and bivalve species collected from eight coastal sites along the
      Chinese Bohai Sea. The total mercury was directly determined by atomic
      fluorescence spectrometry (AFS), while the methylmercury was measured by a
      laboratory established high performance liquid chromatography-atomic fluorescence
      spectrometry system (HPLC-AFS). Certified reference material DORM-2 (Dogfish
      muscle) was used to validate the two methods and the obtained results proved to
      be in good agreement with the certified values. It was demonstrated that the
      mercury contamination was commonly existed in all selected mollusks, with
      methylmercury and total mercury concentration in the range of 4.8-168.4 and 6.7
      453.0 ng Hg g(-)(1), respectively. Mollusks from HuLuDao were the most mercury
      contaminated, and those from PengLai took the second place. The species-dependent
      bioaccumulation capacity was observed in this study. Gastropods showed more
      capacity to bioaccumulate mercury than bivalves, and mercury contents in two
      kinds of gastropods (Rapana venosa and Neverita didyma) presented some uplifted
      trends with the dimensions increasing of the gastropods. Rapana venosa was found
      to be a potential biomarker to monitor mercury pollution in oceans. Evaluations
      were also made concerning about the ratio of methylmercury to total mercury.

PMID- 14640587
TI  - Adsorption and desorption of atrazine, desethylatrazine, deisopropylatrazine, and
      hydroxyatrazine in vegetated filter strip and cultivated soil.
AB  - Adsorption and desorption of atrazine and its metabolites in vegetated filter
      strip soil (VFS) has not been evaluated, yet these data are needed to predict the
      transport of these compounds through the VFS. Adsorption and desorption
      parameters for atrazine, desethylatrazine (DEA), deisopropylatrazine (DIA), and
      hydroxyatrazine (HA) were compared between a cultivated Houston Black clay (CS)
      and an adjacent 12-year-old VFS established in a mixed stand of bermudagrass
      [Cynodon dactylon (L.) Pers.] and buffalograss [Buchloe dactyloides (Nutt.
      Engelm)]. Adsorption and desorption isotherms were determined by batch
      equilibrium. The evaluated chemical and physical properties of the VFS and CS
      were similar with the exception of a 1.7-fold increase in the organic carbon
      content of the VFS. Adsorption and desorption coefficients for atrazine were at
      least 59% higher in VFS than in CS. The adsorption coefficient for HA was 48%
      higher in VFS compared with CS, but desorption was not statistically different
      between soils. Adsorption and desorption coefficients for DEA and DIA were not
      statistically different between soils. The predicted order of mobility in CS is
      HA < atrazine = DIA = DEA. In VFS, the predicted order of mobility is HA <
      atrazine = DIA < DEA. These data indicate that the higher organic carbon in VFS
      will likely retard the transport of atrazine and HA to surface and ground waters;
      however, the transport rates of DEA and DIA will be similar between soils.

PMID- 14640588
TI  - Approaches to spirit aroma: contribution of some aromatic compounds to the
      primary aroma in samples of orujo spirits.
AB  - Terpenes and C(13) norisoprenoids are among the most important aromatic compounds
      found in a volatile and nonvolatile form in grapes. Aromatic typicity of a spirit
      could be attributed to these compounds despite the very important presence of
      volatile compounds produced during alcoholic fermentation. In this study,
      following a solid phase extraction stage, the determination of the varietal
      aromatic compounds by gas chromatography was performed on 15 samples of Galician
      orujo spirits. The results show that significant differences (p < 0.05) exist in
      the concentrations of varietal aromatic compounds in Galician spirits obtained
      from different varieties of grapes. alpha-Ionona is the varietal aromatic
      compound that is most likely to contribute to the aroma of all of the spirits
      studied. The spirits from Catalan Roxo are the most aromatic, with floral and
      fruity nuances, while the spirits from Godello were the less aromatic group as
      far as the varietal compounds studied are concerned. Spirits from Mencia and
      Treixadura show a similar profile, but the former has a more intensive aroma due
      to beta-pinene, citronellol, and alpha-ionone. Albarino spirits stand out because
      of their profile that is marked by the contributions of eugenol and linalool.

PMID- 14640589
TI  - Biogenetic studies in Syringa vulgaris L.: bioconversion of (18)O(2H)-labeled
      precursors into lilac aldehydes and lilac alcohols.
AB  - Syringa vulgaris L. inflorescences, petals, and chloroplasts, isolated from lilac
      flower petals, were fed with aqueous solutions of (18)O-labeled linalool and [5,5
      (2)H(2)]-deoxy-d-xylose (DOX). The chloroplasts of lilac flower petals were
      isolated after feeding experiments with labeled precursors. Volatiles from the
      chloroplasts were extracted by stir bar sorptive extraction (SBSE) and analyzed
      using enantioselective multidimensional gas chromatography-mass spectrometry
      (enantio-MDGC-MS). Feeding experiments with DOX indicate that the novel
      mevalonate-independent 1-deoxy-d-xylose 5-phosphate/2C-methyl-d-erythritol 4
      phosphate (DOX/MEP) is the decisive pathway of lilac aldehyde and lilac alcohol,
      respectively. Bioconversion of [(18)O]linalool into lilac aldehyde and lilac
      alcohol during in vivo feeding experiments was monitored, and the metabolic
      pathways are discussed.

PMID- 14640590
TI  - Antioxidative activities of volatile extracts from green tea, oolong tea, and
      black tea.
AB  - Antioxidative activities of volatile extracts from six teas (one green tea, one
      oolong tea, one roasted green tea, and three black teas) were investigated using
      an aldehyde/carboxylic acid assay and a conjugated diene assay. The samples were
      tested at levels of 20, 50, 100, and 200 micrograms/mL of dichloromethane. The
      results obtained from the two assays were consistent. All extracts except roasted
      green tea exhibited dose-dependent inhibitory activity in the aldehyde/carboxylic
      acid assay. A volatile extract from green tea exhibited the most potent activity
      in both assays among the six extracts. It inhibited hexanal oxidation by almost
      100% over 40 days at the level of 200 micrograms/mL. The extract from oolong tea
      inhibited hexanal oxidation by 50% in 15 days. In the case of the extract from
      roasted green tea, the lowest antioxidative activity was obtained at the level of
      200 micrograms/mL, suggesting that the extract from roasted green tea contained
      some pro-oxidants. The extracts from the three black teas showed slight anti- or
      proactivities in both assays. The major volatile constituents of green tea and
      roasted green tea extracts, which exhibited significant antioxidative activities,
      were analyzed using gas chromatography-mass spectrometry. The major volatile
      chemicals with possible antioxidative activity identified were alkyl compounds
      with double bond(s), such as 3,7-dimethyl-1,6-octadien-3-ol (8.04 mg/kg), in the
      extract from green tea and heterocyclic compounds, such as furfural (7.67 mg/kg),
      in the extract from roasted green tea. Benzyl alcohol, which was proved to be an
      antioxidant, was identified both in a green tea extract (4.67 mg/kg) and in a
      roasted tea extract (1.35 mg/kg).

PMID- 14640591
TI  - Pyruvic acid and acetaldehyde production by different strains of Saccharomyces
      cerevisiae: relationship with Vitisin A and B formation in red wines.
AB  - The production of pyruvate and acetaldehyde by 10 strains of Saccharomyces
      cerevisiae was monitored during the fermentation of Vitis vinifera L. variety
      Tempranillo grape must to determine how these compounds might influence the
      formation of the pyroanthocyanins vitisin A and B (malvidin-3-O-glucoside
      pyruvate acid and malvidin-3-O-glucoside-4 vinyl, respectively). Pyruvate and
      acetaldehyde production patterns were determined for each strain. Pyruvate
      production reached a maximum on day four of fermentation, while acetaldehyde
      production was at its peak in the final stages. The correlation between pyruvate
      production and vitisin A formation was especially strong (R (2) = 0.80) on day 4,
      when the greatest quantity of pyruvate was found in the medium. The correlation
      between acetaldehyde production and the formation of vitisin B was strongest (R
      (2) = 0.81) at the end of fermentation when the acetaldehyde content of the
      medium was at its highest. Identification and quantification experiments were
      performed by HPLC-DAD. The identification of the vitisins was confirmed by LC/ESI
      MS.

PMID- 14640592
TI  - Monovalent salt-induced gelation of enzymatically deesterified pectin.
AB  - Pectin gels were induced by monovalent salts (0.2 M) concurrently with
      deesterification of high methoxy pectin using a salt-independent orange pectin
      methylesterase (PME). Constant pH was maintained during deesterification and
      gelation. If salt or PME was absent, the pectin did not form a gel. The gel
      strength was influenced by both pH and species of monovalent cation. At pH 5.0,
      the pectin gel induced by KCl was significantly stronger than the NaCl-induced
      gel. In contrast, a much stronger gel was produced in the presence of NaCl as
      compared to KCl at pH 7.0. LiCl did not induce pectin gelation at either pH.
      Molecular weights of pectins increased from 1.38 x 10(5) to 2.26 x 10(5) during
      NaCl-induced gelation at pH 7. One proposal to explain these pectin molecular
      weight changes is a hypothetical PME transacylation mechanism. However, these
      pectin molecular weight changes can also be explained by metastable aggregation
      of the enzymatically deesterified low methoxy pectin. We postulate that gelation
      was induced by a slow deesterification of pectin under conditions that would
      normally salt out (precipitate) low methoxy pectin in the absence of PME.

PMID- 14640593
TI  - Fenton-dependent damage to carbohydrates: free radical scavenging activity of
      some simple sugars.
AB  - The antioxidant properties of simple carbohydrates were studied in a chemical
      system. Hydroxyl radicals generated by a Fenton reaction induce damage on simple
      carbohydrates with a consequent free radical scavenging activity. Carbohydrate
      activities were measured by different methods as spin-trapping of hydroxyl
      radical and electron paramagnetic resonance detection and 1,1-diphenyl-2
      picrylhydrazyl quenching. Carbohydrate damage was evaluated in a Fenton system by
      measuring the reactive substances to thiobarbituric acid, by their decreased
      detection with an HPLC test, and by a gas chromatographic determination of formic
      acid from sugar oxidation. Different intensities of damage and scavenging were
      found according to molecular structure, and some hyphotheses on the carbohydrate
      action against free radicals were attempted. The assayed disaccharides were shown
      to be more active toward and less damaged by hydroxyl radical than
      monosaccharides.

PMID- 14640594
TI  - Use of recombinant cyprosin in the manufacture of ewe's milk cheese.
AB  - A recombinant cyprosin from the cardoon (Cynara cardunculus L.) was assayed and
      compared with calf rennet in batches of ewes' milk cheese by determining
      different chemical, biochemical, and microbiological parameters over 4 months of
      ripening. There were no differences between the two types of coagulants in most
      chemical parameters, a(w), and pH. Proteolysis was more marked and rapid in
      cheese containing recombinant cyprosin as coagulant, the soluble nitrogen content
      of which was significantly higher (p < 0.01) than that of the cheese obtained
      with animal rennet; at the end of ripening the nonprotein nitrogen of cheese
      produced with recombinant cyprosin was slightly higher (p > 0.05) as compared
      with that in cheeses obtained with animal rennet. Microbial counts in the milk
      used for making cheese were high in most of the groups analyzed. Despite slight
      differences in counts, the main microbial groups analyzed were similar in cheese
      produced with both types of coagulants throughout ripening.

PMID- 14640595
TI  - Characterization of sulfur speciation in low molecular weight subunits of
      glutenin after reoxidation with potassium iodate and potassium bromate at
      different pH values using x-ray absorption near-edge structure (XANES)
      spectroscopy.
AB  - Sulfur speciation in low molecular weight (LMW) subunits of glutenin after
      reoxidation with potassium iodate and potassium bromate at different pH values,
      aged subunits of glutenin as well as gluten, and gliadin have been investigated
      in situ by S K-edge X-ray absorption near-edge structure (XANES) spectroscopy.
      XANES spectra were analyzed quantitatively using a least-squares fitting routine
      to provide relative percentage contribution of different sulfur species occurring
      in the samples. Using potassium iodate and potassium bromate for reoxidation of
      reduced LMW subunits of glutenin led not only to disulfide states but also to
      higher oxidation states (sulfoxide state, sulfonic acid state). Strongest
      oxidation occurred at low pH values. Higher oxidation states were also
      predominantly detected in the aged subunits of glutenin, whereas the disulfide
      state was the main sulfur species in gluten and gliadin samples. The results
      showed that the oxidation state of sulfur prior to oxidation (thiol, disulfide)
      strongly influences sulfur speciation after oxidation. The choice of the
      oxidizing reagent seems to be of minor importance.

PMID- 14640596
TI  - Protein-lipid interactions in zein films investigated by surface plasmon
      resonance.
AB  - Experiments on the adsorption of alpha-zein (characterized by SDS-PAGE) from
      aqueous ethanol and 2-propanol solutions onto hydrophilic and hydrophobic
      surfaces are reported. Zein adsorption onto self-assembled monolayers (SAMs) was
      detected by surface plasmon resonance (SPR). Gold substrates were prepared by
      thermal evaporation on glass slides. Gold-coated surfaces were modified by
      depositing SAMs of either a long-chain carboxylic acid terminated thiol
      [COOH(CH2)(10)SH] or a methyl-terminated alkanethiol [CH3(CH2)(7)SH].
      Experimental measurements indicated that zein interacted with both hydrophilic
      and hydrophobic surfaces. Zein concentration affected the thickness of bound zein
      layers. The estimated thickness of the zein monolayer deposited on hydrophilic
      surfaces was 4.7 nm. Zein monolayer thickness on hydrophobic surfaces was
      estimated at 4.6 nm. The topography of zein layers was examined by atomic force
      microscopy (AFM) after solvent was evaporated. Surface features of zein deposits
      depended on the adsorbing surface. On hydrophilic surfaces, roughness values were
      high and distinct ring-shaped structures were observed. On hydrophobic surfaces,
      zein formed a uniform and featureless coverage.

PMID- 14640597
TI  - Mobility and distribution of water in cassava and potato starches by 1H and 2H
      NMR.
AB  - Mobility and distribution of water in cassava (rainy and drought crops) and
      potato starches were studied by solid state and NMR relaxometry as a function of
      H(2)O and D(2)O contents ranging from 0 to 44% (dry basis). Measurements of
      relative mobility derived from (2)H solid state NMR were based on relative area
      and line shape analysis. The narrow peak (mobile component) started to show at 5%
      and increased with increasing D(2)O content. This increase in mobile fraction was
      accompanied by a line narrowing. The mobile fractions of deuterons reached a >98%
      level above 15% D(2)O, which is well below the water holding capacity of starch (
      approximately 27%) and the previously assigned "glassy-rubbery transition point"
      (24.3%; Jouppila, K.; Roos, Y. H. The physical state of amorphous corn starch and
      its impact on crystallization. Carbohydr. Polym. 1997, 32, 95-104). This
      reconfirms the liquidlike nature of water in the so-called glassy state of starch
      granules. The plasticization effect of water on starch chains was observed at 14
      17% for cassava and potato starches as indicated by the T(1) minimum. This,
      however, did not seem to relate to the difference observed in swelling among the
      starches studied.

PMID- 14640598
TI  - Simultaneous transgenic suppression of LePG and LeExp1 influences fruit texture
      and juice viscosity in a fresh market tomato variety.
AB  - Tomatoes are grown for fresh consumption or for processing of the fruit. Some
      ripening-associated processes of the fruit can either contribute to or degrade
      attributes associated with both fresh and processing quality. For example, cell
      wall disassembly is associated with loss of fresh fruit firmness as well as with
      loss of processed tomato product viscosity. Several enzymes contribute to cell
      wall polysaccharide disassembly. Polygalacturonase (PG, poly[1,4-alpha-d
      galactouronide] glucanohydrolase, EC 3.2.1.15) is among the most abundant
      polysaccharide hydrolases in ripening tomato fruit and is the major contributor
      to pectin depolymerization. Expansin (LeExp1) is also abundant in ripening fruit
      and is proposed to contribute to cell wall disassembly by nonhydrolytic activity,
      possibly by increasing substrate accessibility to other enzymes. Suppression of
      either LePG or LeExp1 expression alone results in altered softening and/or shelf
      life characteristics. To test whether simultaneous suppression of both LePG and
      LeExp1 expression influences fruit texture in additive or synergistic ways,
      transgenic Lycopersicon esculentum var. Ailsa Craig lines with reduced expression
      of either LePG or LeExp1 were crossed. Fruits from the third generation of
      progeny, homozygous for both transgenic constructs, were analyzed for firmness
      and other quality traits during ripening on or off the vine. In field-grown
      transgenic tomato fruit, suppression of LeExp1 or LePG alone did not
      significantly increase fruit firmness. However, fruits suppressed for both LePG
      and LeExp1 expression were significantly firmer throughout ripening and were less
      susceptible to deterioration during long-term storage. Juice prepared from the
      transgenic tomato fruit with reduced LePG and LeExp1 expression was more viscous
      than juice prepared from control fruit.

PMID- 14640599
TI  - Simultaneous transgenic suppression of LePG and LeExp1 influences rheological
      properties of juice and concentrates from a processing tomato variety.
AB  - Processing tomato lines suppressed in the accumulation of ripening-related
      polygalacturonase or expansin were generated by introduction of transgenes to
      silence expression of the LePG and LeExp1 genes, respectively. The rheological
      properties of juice and juice reconstituted from paste produced from lines
      suppressed in one of these genes, or in both, were compared with azygous
      controls. When assayed by measuring Bostwick consistency, paste produced from
      either suppressed LePG or suppressed LeExp1 lines and diluted to 5 degrees Brix
      was approximately 18% more viscous than that produced from controls. Simultaneous
      suppression of LePG and LeExp1 produced a small additional increase in viscosity
      of 4%. Rheometric flow analysis at 5 or 10 degrees Brix also showed substantial
      increases in the consistency index due to suppression of either LePG or LeExp1
      alone, and a small additional increase when both genes were suppressed in the
      same transgenic line. Measurements by laser diffraction and [1H]NMR showed that
      suppression of LePG or LeExp1 accumulation altered the size distribution of
      insoluble particles and modified their surface properties. The data are
      consistent with suppression of LePG increasing serum viscosity, and suppression
      of either LePG or LeExp1 altering the properties of the insoluble particles and
      improving some aspect of particle-particle or particle-serum interaction, or
      both. However, relative to that caused by suppression of either gene alone, the
      additional increase in viscosity caused by simultaneous suppression of LePG and
      LeExp1 together was slight.

PMID- 14640600
TI  - Transgenic overexpression of expansin influences particle size distribution and
      improves viscosity of tomato juice and paste.
AB  - Suppression of the expression of a ripening-related expansin gene, LeExp1, in
      tomato enhanced fruit firmness and overexpression of LeExp1 resulted in increased
      fruit softening. Because of the incompletely understood relationship between
      fresh fruit texture and the consistency of processed products, we examined the
      effects of LeExp1 overexpression on the processing characteristics of tomato
      fruit. As determined by Bostwick consistency and by controlled strain rheometry,
      juices and pastes prepared from transgenic tomatoes with suppressed LeExp1
      expression had a higher viscosity than preparations from control fruits. However,
      the viscosity of juice and paste prepared from fruit overexpressing LeExp1 was
      significantly greater than products from controls or lines with reduced LeExp1.
      Bostwick consistency increased by 9% (juice) and 6% (paste) in lines with
      suppressed LeExp1 expression but increased by 27.5% (juice) and 19.5% (paste) in
      lines overexpressing LeExp1, relative to controls. Determined by laser
      diffraction, the particles in juice and paste prepared from transgenic fruits
      with reduced LeExp1 expression were smaller, and preparations from fruits
      overexpressing LeExp1 had a size distribution indicating more large particles.
      Analysis of cell wall polysaccharides size indicated that LeExp1 overexpression
      enhanced depolymerization of water soluble pectins as well as tightly bound
      matrix glycans. LeExp1 overexpression may allow increased cell wall hydration,
      resulting in expanded particle size and increased viscosity of products. Because
      either LeExp1 suppression or overexpression leads to improved consistency, the
      interactions that contribute to optimal product rheological properties are
      complex.

PMID- 14640601
TI  - Unfermented rooibos tea: quantitative characterization of flavonoids by HPLC-UV
      and determination of the total antioxidant activity.
AB  - Unfermented rooibos originates from the leaves and the stems of the indigenous
      South African plant, Aspalathus linearis, and it has been reported to have a
      higher content of flavonoids compared to that of fermented rooibos. The HPLC/UV
      method developed in our laboratory for the analysis of the fermented rooibos was
      applied to the quantitative characterization of the major flavonoids present in
      the unfermented rooibos. Main compounds determined were aspalathin (49.92 +/-
      0.80 mg/g), isoorientin (3.57 +/- 0.18 mg/g), orientin (2.336 +/- 0. 049 mg/g),
      and rutin (1.69 +/- 0.14 mg/g), followed in order by isovitexin, vitexin,
      isoquercitrin and hyperoside, quercetin, luteolin and chrysoeryol. The identity
      of detected flavonoids was confirmed by comparing their retention times and UV
      spectra with those of corresponding standards. The total antioxidant activity
      (TAA) of the tea infusions was measured by the ABTS*+ radical cation
      decolorization assay. The TAA of unfermented rooibos (0.8 Trolox meq/g) resulted
      2-fold higher than that of the fermented rooibos. When compared with different
      water infusions of Camellia sinensis (green and black tea), this TAA value was
      about 50% lower.

PMID- 14640602
TI  - Flavonols and anthocyanins of bush butter, Dacryodes edulis (G. Don) H.J. Lam,
      fruit. changes in their composition during ripening.
AB  - Dacryodes edulis is a multipurpose tree presently undergoing domestication in
      central Africa and the countries bordering the Gulf of Guinea, the fruits of
      which are a good source of essential fatty acids. Polyphenols were characterized
      in the skin zone and in the pulp of bush butter [Dacryodes edulis (G. Don) H.J.
      Lam] fruits at different stages of ripeness, from unripe to soft fruits. Total
      polyphenols, assayed according to the Folin-Ciocalteu method, accounted for 3.0
      4.2 mg/g of fresh skin, corresponding to 18.6-21.6 mg/g of defatted dry skin,
      higher concentrations than in the pulp, with 1.1-1.4 mg/g of fresh weight,
      corresponding to 5.4-12.3 mg/g of defatted dry weight. Reversed-phase high
      performance liquid chromatography revealed the presence of flavonols and
      anthocyanins. Flavonols appeared to be the main class, with quercitrin as the
      main individual compound, and the highest concentrations occurred in the skin
      zone. Hyperin, isoquercitrin, isorhamnetin rhamnoside, and isorhamnetin hexoside
      were also present in relatively high amounts. Petunidin, cyanidin, and peonidin
      hexosides were identified by mass spectrometry. In the course of ripening, the
      total polyphenols as well as the major flavonols increased slightly between
      unripe and preripe stages and then declined gradually as ripening progressed.
      Anthocyanin profiles also showed a substantial change during ripening,
      concomitant with the color change from pink to purple.

PMID- 14640603
TI  - Evaluation of antiradical capacity by H2O2-hemin-induced luminol
      chemiluminescence.
AB  - This paper describes a screening method for antioxidant potential determination
      based on luminol/hemin/hydrogen peroxide chemiluminescence. The emission
      depletion, caused by an antiradical compound added during the chemiluminescence
      decay, is proportional to the number of reactive species trapped. Therefore, the
      difference between the areas of the emission decay curves, obtained in the
      absence and in the presence of the potential antioxidant, is a measure for the
      antiradical capacity of the sample. The technique has been applied to measure the
      antiradical capacity of pure compounds and complex mixtures from natural origin,
      providing reliable results that indicate the method's feasibility.

PMID- 14640604
TI  - Chemical and antioxidant properties of Laurocerasus officinalis Roem. (cherry
      laurel) fruit grown in the Black Sea region.
AB  - Laurocerasus officinalis Roem. is a summer fruit highly characteristic of the
      Black Sea region. The edible parts of the fruit were tested for chemical
      composition and antioxidant properties. Total moisture, ash, protein, sugar,
      pectin, ascorbic acid, phenolic, and mineral contents of the fruit were
      determined. The antioxidant activity of the fruit was investigated using TLC
      plate and ferric thiocyanate methods. Its antioxidative character was also tested
      utilizing hydroxyl, DPPH, and superoxide radical scavenging activity
      measurements, using BHT, vitamin C, and Trolox as references. Besides being a
      good source of nutrients, L. officinalis was found to provide a rich source of
      protective antioxidant compounds. Its antioxidant and radical scavenging
      activities were comparable to or higher than those of the reference antioxidants.
      It appeared to have high mineral content. The concentrations of macroelements K,
      Mg, Ca, and Na were high at 2215 +/- 10.5, 179 +/- 11, 153 +/- 0.8, and 55 +/-
      0.3 mg/kg, respectively, and the concentrations of trace elements Mn, Fe, Zn, and
      Cu were 24.2 +/- 1.3, 8.3 +/- 0.8, 1.9 +/- 0.2, and 0.8 +/- 0.1 mg/kg,
      respectively. In addition, the fruit showed very low contents of Pb, Ni, Co, and
      Cr, below the detection limits, which is considered to be a good food quality. As
      it is a rich source of protein, sugar, ascorbic acid, minerals, and antioxidants,
      L. officinalis is well worth further studies regarding its components possessing
      important health benefits and inclusion in the daily diet.

PMID- 14640605
TI  - Capillary electrophoretic determination of theanine, caffeine, and catechins in
      fresh tea leaves and oolong tea and their effects on rat neurosphere adhesion and
      migration.
AB  - Theanine, caffeine, and catechins in fresh tea leaves and oolong tea were
      determined by using capillary electrophoresis (CE). CE separated these tea
      polyphenols from three other tea ingredients, namely, caffeine, theophylline, and
      theanine, within 8 min. The young leaves (apical bud and the two youngest leaves)
      were found to be richer in caffeine, (-)-epigallocatechin gallate (EGCg), and (-)
      epicatechin gallate (ECg) than old leaves (from 5th to 7th leaves). On the other
      hand, the old leaves (from 8th to 10th leaves) contained higher levels of
      theanine, (-)-epigallocatechin (EGC), and (-)-epicatechin (EC). Results from a
      comparison of fresh young tea and oolong tea compositions indicated oolong tea
      contained more theanine and catechins than fresh young tea. Furthermore, it was
      found that the levels of theanine, EGC, and EGCg in young leaves rose markedly
      with the withering process. Caffeine did not markedly change. However, fully or
      partially fermented teas (oolong tea or pauchong tea) have a common initial step
      in the withering process. Fresh tea leaves or oolong tea extract (0.1%, w/v)
      markedly inhibited neurosphere adhesion, cell migration, and neurite outgrowth in
      rat neurospheres. Theanine (348 micrograms/mL) and caffeine at high concentration
      (50 micrograms/mL) did not inhibit neurosphere adhesion or migration activities,
      but EGCg at 20 micrograms/mL effectively inhibited neurosphere adhesion for 24 h.
      These results indicated that EGCg might affect neural stem cell survival or
      differentiation.

PMID- 14640606
TI  - Effect of reducing and oxidizing agents and pH on malt endoproteolytic activities
      and brewing mashes.
AB  - The activities of the four endoproteinase classes of malted barley are known to
      vary with pH, and it seemed likely that the cysteine enzyme activities could be
      altered by redox agents. This study determined how altering the pH and adding
      redox agents to mashes influenced the worts that were produced during the brewing
      process. The reducing agents cysteine.HCl, dithiothreitol, and beta
      mercaptoethanol increased the proteolysis that occurred in malt extracts and
      mashes. This increased proteolysis was negated by the addition of the oxidizing
      agents diamide or hydrogen peroxide. The addition of reducing agents to mashes
      increased the soluble protein, free amino nitrogen (FAN), and extract values of
      their resultant worts, and this effect was abolished by the concomitant addition
      of oxidizing agents. Raising the pH values of the mashes strongly reduced their
      proteolytic activities, soluble protein, FAN, and extract values, but not their
      beta-glucan levels. These results show that several of the major aspects of
      malting and brewing quality can be adjusted by varying the pH and redox
      qualitites of mashes, which could be helpful to brewers. These results also
      strengthen the previous proposal made by Buchanan et al. that the redox status of
      plants may play a significant part in controlling their physiology.

PMID- 14640607
TI  - Screening of foods containing proanthocyanidins and their structural
      characterization using LC-MS/MS and thiolytic degradation.
AB  - A normal-phase HPLC-MS/MS method was applied to screen for proanthocyanidins in
      88 different kinds of foods. Thirty-nine foods were found to contain
      proanthocyanidins. These foods include 19 kinds of fruits, eight cereals/beans,
      seven nuts, two beverages, two spices, and one vegetable. Twenty-five kinds of
      foods were found to contain both oligomeric (DP </= 10) and polymeric
      proanthocyanidins (DP > 10), and the other 14 foods contained only oligomers.
      Procyanidins with B-type linkages were detected as the only components in 21
      foods and also as principal components in the others. Propelargonidins were
      identified in pinto bean, raspberry, strawberry, and almond, etc. Plum, avocado,
      peanut, curry, and cinnamon were identified as potential sources of A-type
      proanthocyanidins in addition to cranberry. Thiolytic degradation and MS/MS
      analyses indicated that the A-type linkages are present as a terminal unit in
      plum or between the extension units in curry, cinnamon, and avocado, whereas A
      type linkages exist at both positions in cranberry and peanut.

PMID- 14640609
TI  - Oligomeric ligands for luminescent and stable nanocrystal quantum dots.
AB  - We report a new family of oligomeric alkyl phosphine ligands for nanocrystal
      quantum dots. These oligomeric phosphines show effective binding affinity to
      quantum dot surfaces. They form thin and secure organic shells that stabilize
      quantum dots in diverse environments including serum and polymer matrices. They
      maintain the initial as-grown photoluminescence quantum yield of the quantum dots
      and enable homogeneous incorporation into various matrices. They present a
      chemically flexible structure that can be used for further chemistry, such as
      cross-linking, copolymerization, and conjugation to biomolecules.

PMID- 14640610
TI  - The dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from
      Haemophilus influenzae is a dinuclear metallohydrolase.
AB  - The Zn K-edge extended X-ray absorption fine structure (EXAFS) spectra, of the
      dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) from
      Haemophilus influenzae have been recorded in the presence of one or two
      equivalents of Zn(II) (i.e. [Zn_(DapE)] and [ZnZn(DapE)]). The Fourier transforms
      of the Zn EXAFS are dominated by a peak at ca. 2.0 A, which can be fit for both
      [Zn_(DapE)] and [ZnZn(DapE)], assuming ca. 5 (N,O) scatterers at 1.96 and 1.98 A,
      respectively. A second-shell feature at ca. 3.34 A appears in the [ZnZn(DapE)]
      EXAFS spectrum but is significantly diminished in [Zn_(DapE)]. These data show
      that DapE contains a dinuclear Zn(II) active site. Since no X-ray
      crystallographic data are available for any DapE enzyme, these data provide the
      first glimpse at the active site of DapE enzymes. In addition, the EXAFS data for
      DapE incubated with two competitive inhibitors, 2-carboxyethylphosphonic acid and
      5-mercaptopentanoic acid, are also presented.

PMID- 14640612
TI  - Direct structure determination of a multicomponent molecular crystal prepared by
      a solid-state grinding procedure.
AB  - A three-component molecular cocrystal material has been prepared by a solvent
      free route involving mechanical grinding of the pure phases of the individual
      components. This material is not accessible from conventional solution-state
      crystallization procedures. Due to the fact that the grinding procedure
      intrinsically leads to a microcrystalline powder sample, the use of powder X-ray
      diffraction data is essential for structure determination. This work emphasizes
      the scope and utility of ab initio structure solution directly from powder X-ray
      diffraction data for carrying out structural characterization of new materials
      prepared via the solid-state grinding route, leading to the opportunity to
      establish structure-property relationships for such materials.

PMID- 14640611
TI  - Biosynthesis of CaCO3 crystals of complex morphology using a fungus and an
      actinomycete.
AB  - The biosynthesis of CaCO3 by reaction of aqueous Ca2+ ions with a fungus,
      Fusarium sp., and an actinomycete, Rhodococcus sp. (both plant organisms), is
      described. In the case of the fungus, cruciform-shaped calcite crystals are
      obtained (SEM picture A) while the actinomycete yielded the unstable polymorph of
      CaCO3, vaterite (SEM picture B). Specific proteins secreted by the microorganisms
      are responsible for the morphology and crystallography control observed. A
      highlight of this approach is that the microorganisms also provide CO2 for
      reaction with the Ca2+ ions, making the crystals completely biogenic.

PMID- 14640613
TI  - Step-enhanced selectivity of NO reduction on platinum-group metals.
AB  - The conversion of NO to N2 is a key issue encountered in the control of emission
      from vehicles. The selectivity of NO reduction on two platinum group metals, Ir
      and Pt, including the close-packed flat surface and the monatomic steps are
      extensively studied within the first-principles density functional theory
      framework. A stepped Ir surface is found to possess high selectivity for NO
      reduction, which is attributed to both the electronic and geometric structures of
      the Ir steps. The other surfaces considered fail to combine both attributes,
      activity and selectivity. In particular, a stepped Pt surface has a poor N2
      selectivity with a large tendency for N2O production. The results explain the
      observed metal dependency and the structure sensitivity of the NO reduction under
      excess O2 conditions.

PMID- 14640614
TI  - Site-specific incorporation of a redox-active amino acid into proteins.
AB  - The redox-active amino acid 3,4-dihydroxy-l-phenylalanine (DHP), which can
      undergo two-electron oxidation to a quinone, has been incorporated selectively
      and efficiently into proteins in Escherichia coli in response to a TAG codon. We
      have demonstrated that DHP can be oxidized electrochemically within the protein.
      The ability to incorporate a redox-active amino acid site specifically into
      proteins should facilitate the study of electron transfer in proteins, as well as
      enable the engineering of redox proteins with novel properties.

PMID- 14640615
TI  - A triplet carbene surviving a week in solution at room temperature.
AB  - A stable triplet carbene, having a lifetime at 25 degrees C of 14.5 days in a
      dilute benzene solution, was realized by simply changing the substituent at the
      10 position of the previously most persistent carbene, di[9-(10
      phenyl)anthryl]carbene, from a phenyl to a 2,6-dimethyl-4-tert-butylphenyl group.

PMID- 14640616
TI  - Determining the solution state orientation of a Ti enolate via stable isotope
      labeling, NMR spectroscopy, and modeling studies.
AB  - Our group has used Ti-promoted aldol additions with an oxazolidineselone as the
      chiral auxiliary with much success. In these reactions, the Se atom in the
      auxiliary both promotes stereospecific addition as well as reports on, through
      the use of 77Se NMR spectroscopy, the ratio of diastereomers produced and the
      geometry of intermediates as the reaction proceeds. Through stable isotope
      labeling and NMR spectroscopy, we are able to experimentally observe a Ti enolate
      in solution and gain insight into its structure and reactivity. Results from
      molecular modeling calculations are also presented for comparison with NMR data.

PMID- 14640617
TI  - Fluorescent, through-bond energy transfer cassettes for labeling multiple
      biological molecules in one experiment.
AB  - Through-bond energy transfer cassettes based on a fluorescein donor component
      electronically conjugated to rhodamine-like acceptors have been designed and
      synthesized. They absorb strongly at 488 nm (Ar-laser emission) and efficiently
      transfer the energy to the acceptor component that emits strongly. Further, the
      cassettes are more stable to photobleaching than fluorescein, making them
      potentially more suitable for single-molecule detection methods than fluorescein
      itself. These studies form the basis for improved detection of chain-terminated
      DNA in high-throughput sequencing and other applications in biotechnology.

PMID- 14640618
TI  - Diversity-oriented synthesis of tamoxifen-type tetrasubstituted olefins.
AB  - A general synthetic scheme for tamoxifen-type tetrasubstituted olefins based on
      the novel Cu-catalyzed carbomagnesation across alkynyl(2-pyridyl)silane has been
      developed. A wide array of electronically and structurally diverse
      tetrasubstituted olefins can be prepared in a regiocontrolled, stereocontrolled,
      and diversity-oriented manner. Noteworthy features are that (i) the three aryl
      groups, which are believed to be important (essential) for anti-estrogenic
      activity, can be varied at will because they all stem from readily available aryl
      iodides, and (ii) any stereo- and regioisomers can, in principle, be prepared by
      simply changing the applying order of aryl iodides into the sequence.

PMID- 14640620
TI  - First direct evidence for stereospecific olefin epoxidation and alkane
      hydroxylation by an oxoiron(IV) porphyrin complex.
AB  - We report in this study that an oxoiron(IV) porphyrin complex bearing electron
      deficient porphyrin ligand, (TPFPP)FeIV=O (TPFPP = meso
      tetrakis(pentafluorophenyl)porphinato dianion), shows reactivities similar to
      those found in oxoiron(IV) porphyrin pi-cation radicals. In the epoxidation of
      olefins by the (TPFPP)FeIV=O complex, epoxides were yielded as major products;
      cyclohexene oxide was the sole product formed in the epoxidation of cyclohexene,
      and stilbenes were stereospecifically oxidized to the corresponding epoxide
      products. More striking results were obtained in alkane hydroxylation reactions;
      the hydroxylation of adamantane afforded a high degree of selectivity for
      tertiary C-H bonds over secondary C-H bonds, and the hydroxylation of cis-1,2
      dimethylcyclohexane yielded a tertiary alcohol product with >99% retention of
      stereochemistry. The latter result demonstrates that an oxoiron(IV) porphyrin
      complex hydroxylates alkanes with a high stereospecificity. Isotope labeling
      studies performed with H218O and 18O2 in the olefin epoxidation and alkane
      hydroxylation reactions demonstrated that oxygen atoms in oxygenated products
      derived from the oxoiron(IV) porphyrin complex.

PMID- 14640619
TI  - Identification from a combinatorial library of a small molecule that selectively
      induces apoptosis in cancer cells.
AB  - The selective induction of death in cancer cells is a major challenge in modern
      medicine. In this communication we describe the synthesis of an 88-membered
      combinatorial library, and the subsequent evaluation of these compounds for their
      ability to selectively induce apoptosis in cancerous cells. A compound was
      identified from the library that induces apoptosis in U-937 and HL-60 cell lines.
      This compound is a remarkably selective pro-apoptotic agent for these cancer cell
      lines, as it does not induce significant death in noncancerous white blood cells,
      even at concentrations as high as 1000 muM.

PMID- 14640621
TI  - Raman dye-labeled nanoparticle probes for proteins.
AB  - In this paper, we demonstrate how one can chemically design Raman dye
      functionalized nanoparticle probes with specific protein-binding affinities and
      use these probes, coupled with surface-enhanced Raman scattering (SERS)
      spectroscopy, to perform multiplexed screening of protein-small molecule
      interactions and protein-protein interactions in a protein microarray format.

PMID- 14640622
TI  - Reversible switching of high-speed air-liquid two-phase flows using
      electrowetting-assisted flow-pattern change.
AB  - This work is the first demonstration of electrical modulation of surface energy
      to reversibly switch dynamic high-speed gas-liquid two-phase microfluidic flow
      patterns. Manipulation of dynamic two-phase systems with continuous high-speed
      flows is complex and interesting due to the multiple types of forces that need to
      be considered. Here, distinct stable flow patterns are formed through a
      multipronged approach: both surface tension forces generated by surface chemistry
      modulation as well as viscous and inertial forces produced by fluid flows are
      employed. The novel fluidic actuation mechanism provides insights into better
      understanding microscale two-phase flow dynamics and offers new opportunities for
      the development of two-phase biochemical microsystems that are mechanically
      simple and operational at high speeds.

PMID- 14640623
TI  - Self-assembly of monodispersed, chiral nanoclusters of cysteine on the Au(110)-(1
      x 2) surface.
AB  - The self-assembly of monodispersed supramolecular nanoclusters was observed by
      scanning tunneling microscopy (STM). The clusters form from the naturally
      occurring amino acid cysteine by vapor deposition onto the Au(110)-(1 x 2)
      surface under ultrahigh vacuum conditions. Enantiomerically pure l- and d
      cysteine yields clusters with mirror-image STM signatures. Racemic ld-cysteine
      segregates into homochiral clusters, evidencing specific intermolecular
      interactions during the self-assembly process.

PMID- 14640624
TI  - Reactivity and molecular recognition: amine methylation by an introverted ester.
AB  - We report a host molecule with an inwardly directed methyl ester and its reaction
      with a series of tertiary amines. The reaction product is a complex of the host
      carboxylate with a guest quaternary ammonium salt. The rate of the reaction is
      highly dependent on the suitability of the amine to occupy the host cavity and
      the intrinsic reactivity of the resulting complex. A kinetic study of the
      reaction of 2-(dimethylamino)ethanol to produce choline gives the activation
      parameters DeltaH = 25.1 +/- 0.5 kcal mol-1 and DeltaS = 12 +/- 2 cal mol-1 K-1.
      The complex, once formed, is poised to reach the transition state; a rate
      acceleration of greater than 2 x 104 fold is estimated when compared with similar
      reactions having no supramolecular effects.

PMID- 14640625
TI  - Detection of heterogeneities in dry and swollen polymer networks by proton low
      field NMR spectroscopy.
AB  - We report on the implementation of modern proton multiple-quantum NMR methods for
      the characterization of molecular order and dynamics in polymer networks and
      melts on cost-efficient low-resolution low-field NMR instrumentation. The method
      permits the extraction of chain order parameter distributions, and is therefore
      sensitive to a heterogeneity of cross-links and other topological constraints.
      Data from samples with bimodal network chain length distributions acquired at 20
      MHz (0.47 T) are in quantitative agreement with results obtained at high field
      (500 MHz). It is shown for the first time that the chain order distribution is
      broadened upon swelling, providing evidence for the nontrivial nature of the
      swelling process.

PMID- 14640626
TI  - Isobutene polymerization using a chelating diborane co-initiator.
AB  - Lewis acidic diborane 1 (J. Am. Chem. Soc. 1999, 121, 3244-3245) is highly
      effective for both proton- and cationogen-initiated isobutene polymerization in
      hydrocarbon media at low temperature. Reactions of diborane 1 with cumyl chloride
      and cumyl methyl ether were studied by variable-temperature 1H and 19F NMR
      spectroscopy. At low temperatures stable ion pairs 2a and 2b are formed; at
      higher temperatures these ion-pairs form phenyl-1,3,3-trimethylindan (3) with
      concomitant release of HCl to form 1 in the case of 2a or degradation of the
      anion (2b). Reaction between Ph3C-Cl and diborane 1 resulted in the generation of
      an ion-pair 4 consisting of the Ph3C cation very weakly associated with the
      chelated, mu-Cl counteranion as revealed by X-ray crystallography.

PMID- 14640627
TI  - Highly selective electrocatalytic conversion of CO2 to CO at -0.57 V (NHE) by
      carbon monoxide dehydrogenase from Moorella thermoacetica.
AB  - We found that CODH is a fascinating enzyme for the electrochemical conversion of
      CO2 to CO. It could reduce CO2 to CO at -0.57 V vs NHE with approximately 100%
      current efficiency in 0.1 M phosphate buffer (pH 6.3). Nature's unique structure
      of C-cluster in CODH would be responsible for the low overpotential and the
      selective and fast conversion of CO2. The turnover number per C-cluster is 700 h
      1, and the pH optimum is 6.3.

PMID- 14640628
TI  - Switching of spin states triggered by a phase transition: spin-crossover
      properties of self-assembled iron(II) complexes with alkyl-tethered triazole
      ligands.
AB  - Iron(II) complexes of triazole derivatives having two C12 and C16 long alkyl
      chains, (C12trz)FeII and (C16trz)FeII, serve as novel spin-crossover materials,
      which display a spin-state transition in response to a phase transition. In
      contrast, a triazole complex with two C8 alkyl chains ((C8trz)FeII) exhibits only
      a poor response. EXAFS and XRD analyses of (C16trz)FeII indicate an
      interdigitating self-assembled structure of polynuclear iron(II) species.
      According to DSC, VT-IR, and VT-XRD profiles, the spin-state transition is
      triggered by melting of the interdigitating alkyl chains, which is likely
      responsible for the "lock-and-release" feature of the spin state. By virtue of
      the thermoreversibility of the phase transition, the spin crossover could be
      repeated without deterioration.

PMID- 14640629
TI  - Studies on the biosynthesis of asperparaline A: origin of the spirosuccinimde
      ring system.
AB  - The primary amino acid building blocks that constitute asperparaline A have been
      determined through feeding and incorporation of 13C-labeled intermediates. The
      beta-methyl proline residue is constituted from (S)-isoleucine, the novel spiro
      succinime moiety is derived from the oxidative degradation of (S)-tryptophan, and
      (S)-adenosylmethionine contributes the two N-methyl residues. In addition, it was
      found that the incorporation of 13C-labeled acetate into the single isoprene unit
      clearly demonstrates that the isoprene moiety is derived from the mevalonate
      pathway.

PMID- 14640630
TI  - Transition-metal-mediated cascade reactions: C,C-dicyclopropylmethylamines by way
      of double C,C-sigma-bond insertion into bicyclobutanes.
AB  - The organometallic multicomponent reaction of alkenyl zirconocene, alkynyl imine,
      and zinc carbenoid in the presence of dimethylzinc leads to novel C,C
      dicyclopropylmethylamines. The formation of intermediate bicyclo[1.1.0]butanes
      represents the first synthetically useful example of a double C,C-sigma-bond
      insertion, and the increase in structural complexity from starting materials is
      highlighted by the formation of nine new C,C-bonds in the final product.

PMID- 14640632
TI  - Excimer formation in the interlayer region of arene-derivatized zirconium
      phosphonates.
AB  - Photophysical investigations are reported for two arene-derivatized zirconium
      phosphonates (layered solids). The chromophore groups that are attached within
      the interlayer region of these materials are seen to form excimer pairs. Whereas
      the naphthalene-containing system exhibits both monomer and excimer fluorescence,
      the potentially greater overlap of chromophores for the system containing
      anthracene-pendant groups causes that compound to only show excimer fluorescence.

PMID- 14640631
TI  - Intramolecular electron transfer in a bacterial sulfite dehydrogenase.
AB  - Sulfite dehydrogenase (SDH) from Starkeya novella, a sulfite-oxidizing molybdenum
      containing enzyme, has a novel tightly bound alphabeta-heterodimeric structure in
      which the Mo cofactor and the c-type heme are located on different subunits.
      Flash photolysis studies of intramolecular electron transfer (IET) in SDH show
      that the process is first-order, independent of solution viscosity, and not
      inhibited by sulfate, which strongly indicates that IET in SDH proceeds directly
      through the protein medium and does not involve substantial movement of the two
      subunits relative to each other. The IET results for SDH contrast with those for
      chicken and human sulfite oxidase (SO) in which the molybdenum domain is linked
      to a b-type heme domain through a flexible loop, and IET shows a remarkable
      dependence on sulfate concentration and viscosity that has been ascribed to
      interdomain docking. The results for SDH provide additional support for the
      interdomain docking hypothesis in animal SO and clearly demonstrate that
      dependence of IET on viscosity and sulfate is not an inherent property of all
      sulfite-oxidizing molybdenum enzymes.

PMID- 14640633
TI  - "Electronic lock" in chromiumtricarbonyl complex of cycloheptatrienyltin.
AB  - The fast sigmatropic [1,5]-Sn migration in cycloheptatrienyl(triphenyl)tin is
      effectively locked in the chromiumtricarbonyl complex. A much slower [1,3]-Sn +
      [1,2]-Cr diatropic rearrangement was detected by spin saturation transfer NMR.

PMID- 14640634
TI  - Enantioselective total synthesis of the potent antitumor agent (-)-mucocin using
      a temporary silicon-tethered ring-closing metathesis cross-coupling reaction.
AB  - The enantioselective total synthesis of the annonaceous acetogenin (-)-mucocin
      (1) was accomplished using a triply convergent 12-step sequence (longest linear
      sequence) in 13.6% overall yield. This represents the first application of the
      temporary silicon-tethered (TST) ring-closing metathesis (RCM) cross-coupling
      reaction and the enantioselective alkyne/aldehyde addition to the synthesis of a
      complex annonaceous acetogenin. Moreover, all three fragments required for the
      coupling reactions are conveniently prepared in 5-6 steps from two readily
      available enantiomerically enriched epoxides. Finally, this synthesis stimulated
      the development of a new approach for the construction of 3-hydroxy-2,6
      disubstituted tetrahydropyrans, using the bismuth tribromide-mediated reductive
      etherification reaction, which represents a motif that is prevalent in a wide
      range of pharmacologically significant natural products.

PMID- 14640635
TI  - Molecularly "engineered" anode adsorbates for probing OLED interfacial structure
      charge injection/luminance relationships: large, structure-dependent effects.
AB  - Molecule-scale structure effects at organic light-emitting diodes (OLED) anode
      organic transport layer interfaces are probed via a self-assembly approach. A
      series of ITO anode-linked silyltriarylamine molecules differing in aryl group
      and linker density are synthesized for this purpose and used to probe the
      relationship between nanoscale interfacial chemical structure, charge injection
      and electroluminescence properties. Dramatic variations in hole injection
      magnitude and OLED performance can be correlated with the molecular structures
      and electrochemically derived heterogeneous electron-transfer rates of such
      triarylamine fragments, placed precisely at the anode-hole transport layer
      interface. Very bright and efficient ( approximately 70 000 cd/m2 and
      approximately 2.5% forward external quantum efficiency) OLEDs have thereby been
      fabricated.

PMID- 14640636
TI  - Carbon nanotube fiber microelectrodes.
AB  - Carbon nanotube (CNT) fibers have been used to fabricate microelectrodes with an
      attractive electrochemical behavior. By combining the advantages of CNT materials
      and fiber microelectrodes, the new material expands the scope of CNT-based
      electrochemical devices. The CNT fiber offers a marked decrease in the
      overvoltage for the NADH, dopamine, and hydrogen peroxide and circumvents NADH
      surface fouling effects. Heat treatment is shown to be extremely useful for
      activating the CNT fiber surfaces for electron transfer. SEM imaging and cyclic
      voltammetric data indicate that the heat treatment leads to the removal of
      nonconducting residues and exposure of a "fresh" CNT surface. The new electrode
      material thus presents new opportunities for a wide range of electrochemical and
      analytical applications.

PMID- 14640637
TI  - Comparison of "polynaphthalenes" prepared by two mechanistically distinct routes.
AB  - The Bergman cyclization has long been known to produce polymers as side products.
      More recently, this attribute has been harnessed for the production of conjugated
      materials. However, the structures of these polymers have not been established.
      To resolve this question, the metal-catalyzed polymerization of 1,4
      dibromonaphthalene and thermal polymerization of o-diethynylbenzene were
      conducted. Two distinct polymers were obtained. Comparison of IR spectroscopy,
      MALDI-TOF MS, solid-state NMR spectroscopy, UV-vis reflectance spectroscopy, and
      pyrolysis GC-MS data indicates that only one of the polymers is consistent with
      poly(1,4-naphthalene).

PMID- 14640638
TI  - Organic/inorganic hybrid vesicles based on a reactive block copolymer.
AB  - Presented in this communication is a novel hybrid vesicle with a cross-linked
      polyorganosiloxane wall based on a new reactive block copolymer, poly(ethylene
      oxide)-block-poly(3-(trimethoxysilyl)propyl methacrylate) (PEO-b-PTMSPMA), which
      was synthesized by atom transfer radical polymerization. The vesicles were
      prepared first by self-assembly of the block copolymer in a selective solvent,
      and then the PTMSPMA block was subjected to hydrolysis and polycondensation
      reaction to fix vesicle wall in the presence of triethylamine as a catalyst.
      Transmission electron microscopy, scanning electron microscopy, NMR, and light
      scattering have been used to characterize the vesicles.

PMID- 14640639
TI  - Early transition-metal perfluoroalkyl complexes.
AB  - Elusive early transition-metal perfluoroalkyl complexes have been isolated and
      structurally characterized for the first time. Trifluoromethyltrimethylsilane,
      CF3SiMe3, serves as an excellent trifluoromethyl group-transfer reagent and
      reacts with the known Ti(IV) fluoride complex Cp2TiF2 to yield the novel Ti(IV)
      trifluoromethyl fluoride compound, Cp2Ti(CF3)(F) (1). Reaction of complex 1 with
      trimethylsilyltriflate (Me3SiOTf) affords the Ti(IV) trifluoromethyl triflate
      complex Cp2Ti(CF3)(OTf) (2). Both titanium perfluoroalkyl compounds have been
      characterized spectroscopically and by single-crystal X-ray analysis. The Ti-CF3
      linkage in these complexes is remarkably robust and shows no evidence of an alpha
      fluoride interaction (Ti...F-CF2) between the electrophilic Ti(IV) metal center
      and any of the C-F bonds in the trifluoromethyl group in the solid state or in
      solution.

PMID- 14640640
TI  - Direct kinetic studies of atom transfer and electron transfer reactions of
      hydroperoxo and high-valent oxo complexes of chromium.
AB  - A macrocyclic hydroperoxo chromium complex reacts with triphenyl phosphine in an
      acid-catalyzed oxygen-atom transfer reaction, k = 850 M-2 s-1. In a competing
      process, the hydroperoxo complex is converted to a dioxo chromium(V) species,
      which reacts with PPh3 by electron transfer, k = 4.4 x 105 M-1 s-1.

PMID- 14640641
TI  - Aptamers switch on fluorescence of triphenylmethane dyes.
AB  - MG and SRB aptamers, which are short RNA sequences originally selected only for
      binding to malachite green or sulforhodamine B, can greatly enhance the
      fluorescence of normally nonfluorescent triphenylmethane dyes. MG aptamer
      enhances the quantum yields of malachite green (MG) and a novel rigidized
      derivative, indolinyl malachite green (IMG) by >2000-fold. SRB aptamer brightens
      patent blue V and VF by >90-fold. These enhancements are specific because MG
      aptamer has no effect on patent blue dyes and SRB aptamer has little or no effect
      on MG and IMG. Such sequence-specific fluorescence labeling of short RNA motifs
      is a first step toward genetically encodable fusion tags for imaging selected
      RNAs in vitro and in cells.

PMID- 14640642
TI  - Photoinduced NO release by visible light irradiation from pyrazine-bridged
      nitrosyl ruthenium complexes.
AB  - The binuclear complex [RuII(NH3)5(pz)RuII(bpy)2(NO)](PF6)5 was prepared and
      characterized by elemental analysis, UV-vis, and IR spectroscopy. The complex UV
      vis spectrum has presented bands at 242, 286, and 530 nm in acetate buffer
      solution at pH 4.5. The photochemical study by laser flash-photolysis at 532 nm
      showed the NO release account from the NO measured by a NO sensor. The quantum
      yield for NO release (0.025 +/- 0.004 mol einsten-1) was determined with a laser
      flash-photolysis apparatus (Continuum Q-switched Nd:YAG laser). The major
      irradiation product of the [RuII(NH3)5(pz)RuII(bpy)2(NO)]5+ complex besides
      nitric oxide is [RuIII(NH3)5(pz)RuII(bpy)2(H2O)]5+.

PMID- 14640643
TI  - Formation of bridging alkene and conjugated dialkenes exclusively generated from
      alkynes on the [3,3'-Co(1,2-C2B9H11)2]- platform. The unique hydroboration role
      of [3,3'-Co(1,2-C2B9H11)2]-.
AB  - The unprecedented metal-mediated transformation of an alkyne into a B,B' bridging
      alkene is reported. Also, the unprecedented synthesis of a conjugated dialkene
      derivative of [3,3'-Co(1,2-C2B9H11)2]- generated only from an alkyne, contrary to
      the usual case where an alkyne and an alkene are needed, is described. This has
      been possible through the singular capacity of a B-H to produce hydroboration.

PMID- 14640645
TI  - Cyclooctanoid ring systems from mixed acetals via heteroatom-assisted [1,2]-shift
      of oxonium ylides.
AB  - Cyclic mixed acetals with pendant diazoketone side chains undergo efficient
      rearrangement to ether-bridged cyclooctanoid systems upon treatment with
      Cu(hfacac)2. This result demonstrates that heterosubstituted carbons are suitable
      migrating groups for the Stevens [1,2]-shift of oxonium ylides. In the case of a
      mixed thioacetal, the resulting sulfide served as a trigger for cleavage of the
      bridging ether through one of two complementary strategies, furnishing a
      bicyclo[6.3.0]octene product with an angular hydroxyl group.

PMID- 14640644
TI  - Total synthesis of (+)-macquarimicin A.
AB  - The first total synthesis of (+)-macquarimicin A (1), a novel inhibitor of
      neutral sphingomyelinase (N-SMase) with antiinflammatory activity, has been
      accomplished. The present work determined the absolute configuration of (+)-1 and
      revised the C(2)-C(3) geometry to be Z. The synthesis features a transannular
      Diels-Alder reaction, which constructed the tetracyclic framework
      stereoselectively, and a convergent and efficient synthetic pathway, which
      afforded (+)-macquarimicin A (1) in 27 steps (longest linear sequence) with 9.9%
      overall yield.

PMID- 14640646
TI  - Cross-couplings of unactivated secondary alkyl halides: room-temperature nickel
      catalyzed Negishi reactions of alkyl bromides and iodides.
AB  - The development of a nickel- or palladium-catalyzed method for cross-coupling
      unactivated secondary alkyl halides has been a long-standing challenge in
      synthetic chemistry. This communication describes a simple catalyst system
      Ni(cod)2/s-Bu-Pybox-that achieves room-temperature Negishi reactions of an array
      of functionalized primary and secondary alkyl bromides and iodides.

PMID- 14640647
TI  - Ligand binding in a docking site of cytochrome C oxidase: a time-resolved step
      scan Fourier transform infrared study.
AB  - The description of reaction regulation in enzymes responsible for activating and
      catalyzing small molecules (O(2), NO) requires identification of ligand movement
      into the binding site and out of the enzyme through specific channels and docking
      sites. We have used time-resolved step-scan Fourier transform infrared
      spectroscopy on CO-photolyzed cytochrome c oxidase ba(3) from T. thermophilus,
      which is responsible for the activation and reduction of both O(2) and NO, to
      gain insight into the structure of ligand-binding intermediates at ambient
      temperature. We show that, upon dissociation, the photolyzed CO becomes trapped
      within a ligand docking site located near the ring A propionate of heme a(3). The
      2131 cm(-1) mode of the "docked" CO we have detected corresponds to the B(1)
      state of Mb and persists for 35 micros. The release of CO from the docking site
      is not followed by recombination to the heme a(3) Fe. Our analysis indicates that
      this behavior reflects a mechanism in which the protein near ring A of heme a(3)
      propionate reorganizes about the released CO from the docking site, and
      establishes a transient barrier that inhibits the recombination process to the
      heme a(3) Fe for a few milliseconds. Rebinding to heme a(3) occurs with k(2) =
      29.5 s(-1). These results have implications for understanding the role of ligand
      binding/escape through docking sites and channels in heme-copper oxidases and,
      thus, in respiration.

PMID- 14640648
TI  - Synthesis and spectroscopic analysis of chromophoric lipids inducing pH-dependent
      liposome fusion.
AB  - We design novel chromophoric amphiphiles 6a-c, which lead to pH-dependent
      membrane fusion of egg phosphatidylcholine (eggPC) liposome containing them.
      Lipids 6a-c comprise double alkyl chains, a single chain with a 2-nitrophenol
      group as a pH trigger, and dipeptide (Asp-Asp) between them. The pKa values of 2
      nitrophenol groups of 6a-c in liposome are larger than that of hydrophilic
      compound 9 in an aqueous solution. Absorption spectra indicate that the fields
      around 2-nitrophenol of 6a-c situated in liposome membranes are more hydrophobic
      than that of 9 in an aqueous solution, whereas the environments around
      deprotonated 2-nitrophenolate of 6b and 6c are not so hydrophobic as that of 6a.
      This means that protonated 2-nitrophenol groups of 6a-c are embedded in bilayer
      membranes. Deprotonated 2-nitrophenol groups of 6b and 6c must be located in less
      hydrophobic circumstances, while that of 6a is still embedded in bilayer
      membranes because of its larger hydrophobicity. Absorption spectra and (1)H NMR
      spectra respectively suggest that protonated 2-nitrophenol groups of 6a and those
      of 6c might take face-to-face associations in bilayer membranes.

PMID- 14640650
TI  - Copper(I) chloride initiated decomposition of 7-phosphanorbornadiene. Evidence
      for a solvent-assisted catalytic mechanism.
AB  - Density functional theory is used to explore the mechanism of the copper(I)
      chloride-catalyzed decomposition of W(CO)(5)-complexed 7-phosphanorbornadiene and
      the subsequent olefin trapping of the terminal phosphinidene complex. CuCl lowers
      the activation barrier by interacting directly with the breaking P-C bond.
      Contrary to the prevailing notion that a free terminal phosphinidene complex
      (W(CO)(5)=PR) is generated in the CuCl-catalyzed cheletropic elimination of the 7
      phosphanorbornadiene-W(CO)(5) complex, the present mechanism suggests that CuCl
      is attached to the terminal phosphinidene. Furthermore, a "chloride shuttle"
      takes place where the chloride first migrates to the phosphorus center and then
      is returned back to the copper center by the incoming olefin in an S(N)2 reaction
      step. When the substituent on phosphorus is a phenyl group (R = Ph), the
      uncatalyzed reaction has an activation barrier of 17.9 kcal/mol, which is reduced
      by 10.9 kcal/mol on including the CuCl catalyst. The CuCl-catalyzed decomposition
      of 7-phosphanorbornadiene followed by olefin trapping of the terminal
      phosphinidene complex has a close parallel with the Cu(I)-catalyzed
      cyclopropanation reaction of diazoalkane. In both catalyzed reactions, copper(I)
      is coordinated to the phosphinidene/carbene as a Lewis acid, while a Lewis base
      is displaced from the phosphorus/carbon center as the olefin is added.

PMID- 14640649
TI  - Supramolecular helices via self-assembly of 8-oxoguanosines.
AB  - The cooperative effect of solvophobic interactions and hydrogen bonding has been
      exploited to self-assemble supramolecular helical architectures of 8
      oxoguanosines in different environments. This self-assembly into helical
      structures is completely different from that of the parent guanosines which, in
      the same experimental conditions, form flat, ribbonlike structures. While optical
      microscopy and X-ray diffraction suggest a chiral columnar aggregate in the LC
      phase, NMR and Circular Dichroism reveal the presence of a helical structures in
      solution. Scanning Tunneling Microscopy made it possible to visualize hexagonally
      arranged G-quartets on graphite, which are sections of the helices packed with
      their long axis perpendicular to the basal plane of the substrate. Due to their
      rectifying electrical properties, such helices are interesting for fabricating
      (opto)electronic biodevices.

PMID- 14640651
TI  - Crystal and molecular structures of ionophore-siderophore host-guest
      supramolecular assemblies relevant to molecular recognition.
AB  - Ionophore-siderophore host-guest assemblies composed of 18-crown-6 and
      ferrioxamine B, benzo-18-crown-6 and ferrioxamine B, and cis-syn-cis
      dicyclohexano-18-crown-6 and ferrioxamine B were successfully crystallized, and
      their structures were determined by single-crystal X-ray diffraction. All three
      crystal lattices also include solvated Mg(II) and perchlorate ions. The ionophore
      siderophore host-guest assembly is noncovalently held together by a hydrogen
      bonding interaction between the pendant protonated amine in the second
      coordination sphere of ferrioxamine B and the hydrogen bond acceptor oxygen atoms
      in the crown ether. The crystals of 18-crown-6:ferrioxamine B host-guest assembly
      are monoclinic, with space group P2(1)/c, and four molecules per unit cell with
      dimensions a = 19.8327(11) A, b = 20.4111(11) A, c = 15.1698(8) A, and beta =
      96.435(1) degrees. The crystals of benzo-18-crown-6:ferrioxamine B host-guest
      assembly are triclinic, with space group P(-)1, and two molecules per unit cell
      with dimensions a = 11.1747(10) A, b = 16.0580(15) A, c = 18.4175(17) A, alpha =
      80.469(3) degrees, beta = 81.481(3) degrees and gamma = 70.212(2) degrees. The
      crystals of cis-syn-cis-dicyclohexano-18-crown-6:ferrioxamine B host-guest
      assembly are monoclinic, with space group P2(1)/c, and four molecules per unit
      cell with dimensions a = 20.1473(13) A, b = 21.5778(15) A, c = 14.8013(10) A, and
      beta = 94.586(2) degrees. The crystal structures of all three host-guest
      assemblies contain a racemic mixture of Lambda-N-cis, cis and Delta-N-cis, cis
      coordination isomers of ferrioxamine B. The crystal structures indicate that the
      steric rigidity of the benzo-18-crown-6 and cis-syn-cis-dicyclohexano-18-crown-6
      cavity has a pronounced effect on the conformation of the crown ring and
      ultimately on the hydrogen bonding interactions between the crown ethers and
      ferrioxamine B. The structural parameters and the conformational features of the
      ferrioxamine B guests compare very well with each other and with those of the
      ferrioxamine B structure obtained in the absence of a host. Structural features
      relevant to siderophore molecular recognition are discussed.

PMID- 14640652
TI  - C2-symmetric bis(oxazolinato)lanthanide catalysts for enantioselective
      intramolecular hydroamination/cyclization.
AB  - C(2)-symmetric bis(oxazolinato)lanthanide complexes of the type [(4R,5S)
      Ph(2)Box]La[N(TMS)(2)](2), [(4S,5R)-Ar(2)Box]La[N(TMS)(2)](2), and [(4S)-Ph-5,5
      Me(2)Box]La[N(TMS)(2)](2) (Box = 2,2'-bis(2-oxazoline)methylenyl; Ar = 4-tert
      butylphenyl, 1-naphthyl; TMS = SiMe(3)) serve as precatalysts for the efficient
      enantioselective intramolecular hydroamination/cyclization of aminoalkenes and
      aminodienes. These new catalyst systems are conveniently generated in situ from
      the known metal precursors Ln[N(TMS)(2)](3) or Ln[CH(TMS)(2)](3) (Ln = La, Nd,
      Sm, Y, Lu) and 1.2 equiv of commercially available or readily prepared
      bis(oxazoline) ligands such as (4R,5S)-Ph(2)BoxH, (4S,5R)-Ar(2)BoxH, and (4S)-Ph
      5,5-Me(2)BoxH. The X-ray crystal structure of [(4S)-(t)BuBox]Lu[CH(TMS)(2)](2)
      provides insight into the structure of the in situ generated precatalyst species.
      Lanthanides having the largest ionic radii exhibit the highest turnover
      frequencies as well as enantioselectivities. Reaction rates maximize near 1:1
      BoxH:Ln ratio (ligand acceleration); however, increasing the ratio to 2:1 BoxH:Ln
      decreases the reaction rate, while affording enantiomeric excesses similar to the
      1:1 BoxH:Ln case. A screening study of bis(oxazoline) ligands reveals that aryl
      stereodirecting groups at the oxazoline ring 4 position and additional
      substitution (geminal dimethyl or aryl) at the 5 position are crucial for high
      turnover frequencies and good enantioselectivities. The optimized precatalyst, in
      situ generated [(4R,5S)-Ph(2)Box]La[N(TMS)(2)](2), exhibits good rates and
      enantioselectivities, comparable to or greater than those achieved with chiral
      C(1)-symmetric organolanthanocene catalysts, even for poorly responsive
      substrates (up to 67% ee at 23 degrees C). Kinetic studies reveal that
      hydroamination rates are zero order in [amine substrate] and first order in
      [catalyst], implicating the same general mechanism for organolanthanide-catalyzed
      hydroamination/cyclizations (intramolecular turnover-limiting olefin insertion
      followed by the rapid protonolysis of an Ln-C bond by amine substrate) and
      implying that the active catalytic species is monomeric.

PMID- 14640653
TI  - Spectroscopic studies of the Met182Thr mutant of nitrite reductase: role of the
      axial ligand in the geometric and electronic structure of blue and green copper
      sites.
AB  - A combination of spectroscopic methods and density functional calculations has
      been used to describe the electronic structure of the axial mutant (Met182Thr) of
      Rhodobacter sphaeroides nitrite reductase in which the axial methionine has been
      changed to a threonine. This mutation results in a dramatic change in the
      geometric and electronic structure of the copper site. The electronic absorption
      data imply that the type 1 site in the mutant is like a typical blue copper site
      in contrast to the wild-type site, which is green. Similar ligand field strength
      in the mutant and the wild type (from MCD spectra) explains the similar EPR
      parameters for very different electronic structures. Resonance Raman shows that
      the Cu-S(Cys) bond is stronger in the mutant relative to the wild type. From a
      combination of absorption, CD, MCD, and EPR data, the loss of the strong axial
      thioether (present in the wild-type site) results in an increase of the
      equatorial thiolate-Cu interaction and the site becomes less tetragonal.
      Spectroscopically calibrated density functional calculations were used to provide
      additional insight into the role of the axial ligand. The calculations reproduce
      well the experimental ground-state bonding and the changes in going from a green
      to a blue site along this coupled distortion coordinate. Geometry optimizations
      at the weak and strong axial ligand limits show that the bonding of the axial
      thioether is the key factor in determining the structure of the ground state. A
      comparison of plastocyanin (blue), wild-type nitrite reductase (green), and the
      Met182Thr mutant (blue) sites enables evaluation of the role of the axial ligand
      in the geometric and electronic structure of type 1 copper sites, which can
      affect the electron-transfer properties of these sites.

PMID- 14640654
TI  - Adsorbed surfactants as templates for the synthesis of morphologically controlled
      polyaniline and polypyrrole nanostructures on flat surfaces: from spheres to
      wires to flat films.
AB  - Nanostructures of polyaniline (PAni) and polypyrrole (PPy) with controlled
      morphologies have been synthesized on atomically flat surfaces using adsorbed
      surfactant molecules as templates. Atomic force microscopy (AFM) has been used to
      investigate polymer film formation on highly oriented pyrolytic graphite (HOPG)
      and chemically modified HOPG. Morphological control over the resulting polymer
      film is possible by the addition of coadsorbing molecules, manipulation of the
      length of the surfactant hydrophobe, or by changing the surface chemistry of the
      adsorbing substrate. Phase transitions between spheres, cylinders/wires, and
      featureless films have been observed which exactly parallel transitions between
      spheres, cylinders, and flat layers in the adsorbed surfactant. Parallel arrays
      of PAni nanowires can be synthesized with alignment evident over large areas in a
      simple self-assembly technique in which fabrication and arrangement take place
      simultaneously. Such a technique in which one can engineer sub-100-nm-ordered
      nanoscale pi-conjugated polymer structures of a desired shape by a simple self
      assembly process presents potential as templates, sensors, and microelectronic
      devices.

PMID- 14640655
TI  - The standard redox potential of the phenyl radical/anion couple.
AB  - The voltammogram of aryldiazonium tetrafluoroborates in acetonitrile (ACN), at
      low concentration, shows a first one-electron wave followed at a more negative
      potential by a small second wave; this last one corresponds to the reduction of
      the radical formed at the level of the first wave. Simulation of the voltammogram
      permits one to determine the standard redox potential of the radical/anion couple
      Eo(Ph./Ph-) = 0.05 V/SCE and the reduction mechanism of the diazonium cation. An
      electron transfer concerted with the cleavage of the C-N bond furnishes the aryl
      radical; this radical undergoes two competitive reactions: reduction at the
      electrode and H-atom transfer.

PMID- 14640656
TI  - Energetics of phosphate binding to ammonium and guanidinium containing metallo
      receptors in water.
AB  - The design and synthesis of receptors containing a Cu(II) binding site with
      appended ammonium groups (1) and guanidinium groups (2), along with
      thermodynamics analyses of anion binding, are reported. Both receptors 1 and 2
      show high affinities (10(4) M(-1)) and selectivities for phosphate over other
      anions in 98:2 water:methanol at biological pH. The binding of the host-guest
      pairs is proposed to proceed through ion-pairing interactions between the charged
      functional groups on both the host and the guest. The affinities and
      selectivities for oxyanions were determined using UV/vis titration techniques.
      Additionally, thermodynamic investigations indicate that the 1:phosphate complex
      is primarily entropy driven, while the 2:phosphate complex displays both
      favorable enthalpy and entropy changes. The thermodynamic data for binding
      provide a picture of the roles of the host, guest, counterions, and solvent. The
      difference in the entropy and enthalpy driving forces for the ammonium and
      guanidinium containing hosts are postulated to derive primarily from differences
      in the solvation shell of these two groups.

PMID- 14640657
TI  - Structures, electronic states, and electroluminescent properties of a zinc(II) 2
      (2-hydroxyphenyl)benzothiazolate complex.
AB  - Bis(2-(2-hydroxyphenyl)benzothiazolate)zinc (Zn(BTZ)(2)) is one of the best white
      electroluminescent materials used in organic light-emitting diodes (LEDs).
      Despite a large number of studies devoted to this complex, very little is known
      about its basic molecular and electronic structures and electron transport
      properties in LEDs. Therefore, we investigate the structures and
      electroluminescent properties. The unsolvated single crystal of Zn(BTZ)(2) was
      grown and its crystalline structure was determined from X-ray diffraction data.
      The crystal is triclinic, space group P-1, a = 9.4890(19) A, b = 9.5687(19) A, c
      = 11.685(2) A, alpha = 84.38(3) degrees, beta = 78.94(3) degrees, gamma =
      83.32(3) degrees. The structure of the chelate is dimeric [Zn(BTZ)(2)](2) with
      two isotropic Zn(2+) ion centers having five-coordinate geometry. The present
      study provides direct evidence for the sole existence of dimeric structure in the
      powder and the thin film. The dimer is energetically more stable than the
      monomer. Analysis of the electronic structure of [Zn(BTZ)(2)](2) calculated by
      density functional theory reveals a localization of orbital and the distribution
      of four orbital "tetrads". The structural stabilities of both anion and cation
      and the distribution of the hole in the cation and that of the excess electron in
      the anion are discussed in terms of theoretical calculations. Strong
      intermolecular interaction may be expected to enable good electron transport
      properties as compared with tris(8-hydroxyquinolinato)aluminum.

PMID- 14640658
TI  - Circular dichroism imaging microscopy: application to enantiomorphous twinning in
      biaxial crystals of 1,8-dihydroxyanthraquinone.
AB  - A microscope was constructed for imaging circular dichroism of heterogeneous
      anisotropic media. To avoid linear biases that are common with electronic
      circular polarization modulation, we chose a retrogressive solution: mechanical
      light modulation by rotating a linear polarizer with respect to a quarter wave
      plate continuously tuned by tilting to the operating wavelength. Our
      comparatively slow technique succeeds with near-perfect circular input and signal
      averaging using a CCD camera. We have applied the method to anomalously
      birefringent crystals of 1,8-dihydroxyanthraquinone that are shown to have
      intergrown mirror image domains, undetected by X-ray diffraction because the
      twinning complexity renders differences in anomalous dispersion, already small,
      unreliable. The origin of the anomalous birefringence and the assignment of the
      absolute configuration are discussed.

PMID- 14640659
TI  - Dendrimer-encapsulated nanoparticle precursors to supported platinum catalysts.
AB  - In this contribution, we report the successful preparation of supported metal
      catalysts using dendrimer-encapsulated Pt nanoparticles as metal precursors.
      Polyamidoamine (PAMAM) dendrimers were first used to template and stabilize Pt
      nanoparticles prepared in solution. These dendrimer-encapsulated nanoparticles
      were then deposited onto a commercial high surface area silica support and
      thermally activated to remove the organic dendrimer. The resulting materials are
      active oxidation and hydrogenation catalysts. The effects of catalyst preparation
      and activation on activity for toluene hydrogenation and CO oxidation catalysis
      are discussed.

PMID- 14640660
TI  - Direct growth of shape-controlled nanocrystals on nanotubes via biological
      recognition.
AB  - The new biological approach was examined to fabricate shape-controlled Ag
      nanocrystals grown directly on surfaces, inspired by nature that various shapes
      of nanocrystals are produced accurately and reproducibly in biological systems.
      Here we demonstrate the direct growth of hexagon-shaped Ag nanocrystals on
      sequenced peptide-coated nanotubes via biological recognition. When the peptide,
      Asn-Pro-Ser-Ser-Leu-Phe-Arg-Tyr-Leu-Pro-Ser-Asp, recognizing and effecting the Ag
      nanocrystal growth on the (111) face, was sequenced and incorporated onto
      template nanotube surfaces, the biomineralization of Ag ions on the nanotubes led
      the isotropic hexagon-shaped Ag nanocrystal coating under pH control of the
      growth solution. Multiple Ag nanocrystal shapes were observed when the peptide
      mineralized Ag ions without the template nanotubes, and therefore the template
      nanotube has a significant influence on regulating the majority of Ag
      nanocrystals into the hexagonal shape. This biological approach, using specific
      peptide sequences on surfaces to control nanocrystal shapes, may be developed as
      a simple and economical method to produce building blocks with desired physical
      properties for new generation of electronics, sensors, and optical devices.

PMID- 14640661
TI  - Ab initio folding of helix bundle proteins using molecular dynamics simulations.
AB  - We have demonstrated that ab initio fast folding simulations at 400 K using a GB
      implicit solvent model with an all-atom based force field can describe the
      spontaneous formation of nativelike structures for the 36-residue villin
      headpiece and the 46-residue fragment B of Staphylococcal protein A. An implicit
      solvent model combined with high-temperature MD makes it possible to perform
      direct folding simulations of small- to medium-sized proteins by reducing the
      computational requirements tremendously. In the early stage of folding of the
      villin headpiece and protein A, initial hydrophobic collapse and rapid formation
      of helices were found to play important roles. For protein A, the third helix
      forms first in the early stage of folding and exhibits higher stability. The free
      energy profiles calculated from the folding simulations suggested that both of
      the helix-bundle proteins show a two-state thermodynamic behavior and protein A
      exhibits rather broad native basins.

PMID- 14640662
TI  - Acrylate formation via metal-assisted C-C coupling between CO2 and C2H4: reaction
      mechanism as revealed from density functional calculations.
AB  - The reaction path for the formation of a binuclear hydrido-acrylate complex in a
      CO(2)-C(2)H(4) coupling process is explored in detail by locating the key
      intermediates and transition states on model potential energy surfaces derived
      from density functional calculations on realistic models. The formation of the
      new C-C bond is shown to take place via oxidative coupling of coordinated CO(2)
      and C(2)H(4) ligands resulting in a metalla-lactone intermediate, which can
      rearrange to an agostic species allowing for a beta-hydrogen shift process. The
      overall reaction is predicted to be clearly exothermic with all intermediates
      lying below the reactants in energy, and the highest barrier steps correspond to
      C-C coupling and beta-hydrogen transfer. The phosphine ligands are found to play
      an important role in various phases of the reaction as their dissociation
      controls the coordination of CO(2), the formation of the agostic intermediate,
      and the dimerization process; furthermore, their presence facilitates the
      oxidative coupling by supplying electrons to the metal center. Our results
      provide a theoretical support for the reaction mechanism proposed from
      experimental observations. The effect of the solvent medium on the relative
      energy of reaction intermediates and transition states is examined and found
      important in order to predict reliable energetics.

PMID- 14640663
TI  - On the value of c: can low affinity systems be studied by isothermal titration
      calorimetry?
AB  - Isothermal titration calorimetry (ITC) allows the determination of DeltaG
      degrees, DeltaH degrees, and DeltaS degrees from a single experiment and is thus
      widely used for studying binding thermodynamics in both biological and synthetic
      supramolecular systems. However, it is widely believed that it is not possible to
      derive accurate thermodynamic information from ITC experiments in which the
      Wiseman "c" parameter (which is the product of the receptor concentration and the
      binding constant, K(a)) is less than ca. 10, constraining its use to high
      affinity systems. Herein, experimental titrations and simulated data are used to
      demonstrate that this dogma is false, especially for low affinity systems,
      assuming that (1) a sufficient portion of the binding isotherm is used for
      analysis, (2) the binding stoichiometry is known, (3) the concentrations of both
      ligand and receptor are known with accuracy, and (4) there is an adequate level
      of signal-to-noise in the data. This study supports the validity of ITC for
      determining the value of K(a) and, hence, DeltaG degrees from experiments
      conducted under low c conditions but advocates greater caution in the
      interpretation of values for DeltaH degrees. Therefore, isothermal titration
      calorimetry is a valid and useful technique for studying biologically and
      synthetically important low affinity systems.

PMID- 14640664
TI  - One-bond, two-bond, and three-bond mechanisms in thermal deazetizations of 2,3
      diazabicyclo[2.2.2]oct-2-enes, trans-azomethane, and 2,3-diazabicyclo[2.2.1]hept
      2-ene.
AB  - The thermal deazetizations of a series of substituted 2,3-diazabicyclo[2.2.2]oct
      2-enes and some simpler model systems have been studied using the UB3LYP/6-31G(d)
      and CASPT2 methods, with a variety of active spaces. A fused cyclopropane exerts
      unique control on the mechanism and rate of deazetization. When the Walsh sigma
      orbitals are appropriately aligned in an exo orientation, a pericyclic three-bond
      cleavage occurs. For an endo-fused cyclopropane, sequential one-bond cleavages
      occur to take advantage of orbital overlap with the Walsh orbitals. In systems
      lacking strongly directing substituents, concerted two-bond cleavage pathways to
      form diradical intermediates have a small enthalpic advantage (DeltaH(0K)++) over
      sequential one-bond cleavage pathways. However, the one-bond mechanism has an
      entropic advantage over the two-bond; consequently, at 400-500 K where
      decomposition occurs, one-bond and two-bond diradical cleavages both occur
      simultaneously. The thermal decompositions of trans-azomethane and 2,3
      diazabicyclo[2.2.1]hept-2-ene are also studied, and the results are compared to
      extensive computational studies in the literature. Comparisons of UB3LYP, CASSCF,
      and CASPT2 surfaces for these reactions are made.

PMID- 14640665
TI  - Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes:
      application of halide effects in the development of a general process.
AB  - We have demonstrated halide effects in the rhodium-catalyzed asymmetric ring
      opening reaction of oxabicyclic alkenes. By employing halide and protic
      additives, the catalyst poisoning effect of aliphatic amines is reversed allowing
      the amount nucleophile to react in high yield and ee. Second, by simply changing
      the halide ligand on the rhodium catalyst from chloride to iodide, the reactivity
      and enantioselectivity of reactions employing an aromatic amine, malonate or
      carboxylate nucleophile are dramatically improved. Third, through the application
      of halide effects and more forcing reaction conditions, less reactive oxabicycle
      [2.2.1] substrates react to generate synthetically useful enantioenriched
      cyclohexenol products. Application of these new conditions to the more reactive
      oxabenzonorbornadiene permits the reaction to be run with very low catalyst
      loadings (0.01 mol %).

PMID- 14640666
TI  - Sidewall functionalization of single-walled carbon nanotubes by addition of
      dichlorocarbene.
AB  - We report the sidewall functionalization of soluble HiPco single-walled carbon
      nanotubes (SWNTs) by addition of dichlorocarbene. The dichlorocarbene
      functionalized SWNTs [(s-SWNT)CCl(2)] retain their solubility in organic solvents
      such as tetrahydrofuran and dichlorobenzene. The degree of dichlorocarbene
      functionalization was varied between 12% and 23% by using different amounts of
      the dichlorocarbene precursor. Because the addition of dichlorocarbene saturates
      the carbon atoms on the sidewall of the SWNTs and effectively replaces the
      delocalized partial double bonds with a cyclopropane functionality, the optical
      spectra of the SWNTs change dramatically. We estimate that the saturation of 25%
      of the pi-network electronic structure of the SWNTs is sufficient to remove all
      vestiges of the interband transitions in the infrared spectrum. The transitions
      at the Fermi level in the metallic SWNTs that appear in the far-infrared (FIR)
      region of the spectrum show a dramatic decrease of intensity on dichlorocarbene
      functionalization. The FIR region of the spectrum allows a clear differentiation
      between the covalent and the ionic chemistry of SWNTs. In contrast with covalent
      functionalization, we show that reaction of the SWNTs with bromine vapor leads to
      a strong increase in absorptions at the Fermi level that is observable in the FIR
      due to hole doping of the semiconducting SWNTs. Thermal treatment of the (s
      SWNT)CCl(2) above 300 degrees C resulted in the breakage of C-Cl bonds, but did
      not restore the original electronic structure of the SWNTs.

PMID- 14640667
TI  - Ring-opening metathesis/oxy-cope rearrangement: a new strategy for the synthesis
      of bicyclic medium ring-containing compounds.
AB  - Ring-opening/ring-closing metathesis on cyclobutene-containing substrates with
      angular oxygen functionality provides a stereospecific introduction of 1,5-bis
      dienes required for an anion-accelerated oxy-Cope rearrangement. The reaction
      sequence offers generally a stereocontrolled preparation of a variety of medium
      ring-containing bicyclic ring systems, while rearrangement to the
      bicyclo[7,3,0]dodecane (9-5) system leads to a mixture of olefin isomers.

PMID- 14640668
TI  - Formation and cleavage of aromatic disulfide radical anions.
AB  - The electron transfer (ET) to a series of para-substituted diaryl disulfides,
      having the general formula (X-C(6)H(4)S-)(2), has been studied. The X groups were
      selected as to have a comprehensive variation of the substituent effect, being X
      = NH(2), MeO, H, F, Cl, CO(2)Et, CN, and NO(2). The reduction was carried out
      experimentally, using N,N-dimethylformamide as the solvent, and by molecular
      orbital (MO) ab initio calculations. The ET was studied heterogeneously, by
      voltammetric reduction and convolution analysis, and homogeneously, by using
      electrogenerated radical anions as the solution electron donors. The reduction is
      dissociative, leading to the cleavage of the S-S bond in a stepwise manner. Both
      experimental approaches led us to estimate the E degrees and the intrinsic
      barrier values for the formation of the radical anions. Comparison of the
      independently obtained results allowed obtaining, for the first time, a
      quantitative description of the correlation between heterogeneous and homogeneous
      rate constants of ETs associated with significant inner reorganization energy.
      The experimental outcome was fully supported by the theoretical calculations,
      which provided information about the disulfide lowest unoccupied MOs (LUMOs) and
      singly occupied MO (SOMO), the bond dissociation energies, and the most
      significant structural modifications associated with radical anion formation.
      With disulfides bearing electron-donating or mildly electron-withdrawing groups,
      the inner reorganization is particularly large, which reflects the significant
      stretching of the S-S bond experienced by the molecule upon ET. The process
      entails formation of loose radical anion species in which the SOMO is heavily
      localized, as the LUMO, onto the frangible bond. As a consequence of the
      formation of these sigma-radical anions, the S-S bond energy of the latter is
      rather small and the cleavage rate constant is very large. With electron
      withdrawing groups, the extent of delocalization of the SOMO onto the aryl system
      increases, leading to a decrease of the reorganization energy for radical anion
      formation. Interestingly, while the LUMO now has pi character, the actual
      reduction intermediate (and thus the SOMO) is still a sigma-type radical anion.
      With the nitro-substituted disulfide, very limited inner reorganization is
      required and a pi-radical anion initially forms. A nondissociative type
      intramolecular ET then ensues, leading to the formation of a new radical anion
      whose antibonding orbital has similar features as those of the SOMO of the other
      diaryl disulfides. Therefore, independently of the substituent, the actual S-S
      bond cleavage occurs in a quite similar way along the series investigated. The S
      S bond cleavage rate, however, tends to decrease as the Hammett sigma increases,
      which would be in keeping with an increase of both the electronic and solvent
      reorganization energies.

PMID- 14640669
TI  - Selective solid state photooxidant.
AB  - Irradiation of biphenyl encapsulated in the cavities of a NaZSM-5 zeolite
      framework has been reported to result in the formation of an extremely long-lived
      radical cation. Here, we show that such zeolite encapsulated radical cations can
      act as irreversible one-electron oxidants for simple alkenes and dienes, in a
      solid-state analogue to solution-phase cosensitization. Compared to the well
      known semiconductor photooxidizers, such as titanium dioxide, the NaZSM-5 zeolite
      based solid photooxidants exhibit enhanced selectivity based on oxidation
      potential, molecular size and shape, and Lewis base character.

PMID- 14640670
TI  - Vibrational response of nanorods to ultrafast laser induced heating: theoretical
      and experimental analysis.
AB  - In this paper, we elucidate the vibrational response of cylindrical nanorods to
      ultrafast laser-induced heating. A theoretical analysis of the expected behavior
      is first presented. This analysis predicts that both extensional and breathing
      vibrational modes of the rods should be excited by laser-induced heating.
      Analytical formulas are derived assuming that the heating/expansion process is
      instantaneous, and that the lengths of the rods are much greater than their
      radii. These results show that the breathing mode dominates the mechanical
      deformation of the rod. However, because the frequency of the extensional mode is
      much lower than that of the breathing mode, the extensional mode will dominate
      the response for a real experiment (a finite-time heating/expansion process). The
      results of this model are compared to data from transient absorption experiments
      performed on gold nanorods with average lengths between 30 and 110 nm. The
      transient absorption traces show pronounced modulations with periods between 40
      and 120 ps, which are only observed when the probe laser is tuned to the
      longitudinal plasmon band. The measured periods are in good agreement with the
      expected values for the extensional modes of the rods. For rods wider than 20 nm,
      the breathing mode can also be observed and, again, the measured periods are in
      good agreement with the theoretical calculations. The breathing mode is not
      observed for thinner rods (<20 nm width) because, in this case, the period is
      comparable to the time scale for lattice heating.

PMID- 14640671
TI  - Photochemistry of 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate: an experimental
      and computational investigation.
AB  - The aqueous photochemistry of the sodium salt of 1-(N,N-diethylamino)-diazen-1
      ium-1,2-diolate (3) has been investigated by both experimental and computational
      methods. Photolysis results in the formation of the N-nitrosodiethylamine radical
      anion (5) and nitric oxide (NO) via a triplet excited state. The nitrosamine
      radical anion either undergoes electron transfer with NO before cage escape to
      form triplet NO(-) and nitrosamine (minor process) or rapidly dissociates to form
      an additional molecule of NO and ultimately amine (major process). The production
      of nitrosamine radical anion 5 upon photolysis of diazeniumdiolate 3 is confirmed
      by low-temperature EPR spectroscopy. The calculated energetics for the ground and
      excited states of the parent diazeniumdiolate ion at the CIS and B3LYP levels of
      theory as well as B3LYP calculations on the fragmentation processes were very
      effective in rationalizing the observed photodissociation processes.

PMID- 14640672
TI  - Chelate effect and thermodynamics of metal complex formation in solution: a
      quantum chemical study.
AB  - The accuracy of quantum chemical predictions of structures and thermodynamic data
      for metal complexes depends both on the quantum chemical methods and the chemical
      models used. A thermodynamic analogue of the Eigen-Wilkins mechanism for ligand
      substitution reactions (Model A) turns out to be sufficiently simple to catch the
      essential chemistry of complex formation reactions and allows quantum chemical
      calculations at the ab initio level of thermodynamic quantities both in gas phase
      and solution; the latter by using the conductor-like polarizable continuum (CPCM)
      model. Model A describes the complex formation as a two-step reaction: 1.
      [M(H2O)x](aq) + L(aq) <==>[M(H2O)x], L(aq); 2. [M(H2O)x], L(aq) <==>[M(H2O)(x
      1)L],(H2O)(aq). The first step, the formation of an outer-sphere complex is
      described using the Fuoss equation and the second, the intramolecular exchange
      between an entering ligand from the second and water in the first coordination
      shell, using quantum chemical methods. The thermodynamic quantities for this
      model were compared to those for the reaction: [M(H2O)x](aq) + L(aq)
      <==>[M(H2O)(x-1)L](aq) + (H2O)(aq) (Model B), as calculated for each reactant and
      product separately. The models were tested using complex formation between Zn(2+)
      and ammonia, methylamine, and ethylenediamine, and complex formation and chelate
      ring closure reactions in binary and ternary UO(2)(2+)-oxalate systems. The
      results show that the Gibbs energy of reaction for Model A are not strongly
      dependent on the number of water ligands and the structure of the second
      coordination sphere; it provides a much more precise estimate of the
      thermodynamics of complex formation reactions in solution than that obtained from
      Model B. The agreement between the experimental and calculated data for the
      formation of Zn(NH(3))(2+)(aq) and Zn(NH(3))(2)(2+)(aq) is better than 8 kJ/mol
      for the former, as compared to 30 kJ/mol or larger, for the latter. The Gibbs
      energy of reaction obtained for the UO(2)(2+) oxalate systems using model B
      differs between 80 and 130 kJ/mol from the experimental results, whereas the
      agreement with Model A is better. The errors in the quantum chemical estimates of
      the entropy and enthalpy of reaction are somewhat larger than those for the Gibbs
      energy, but still in fair agreement with experiments; adding water molecules in
      the second coordination sphere improves the agreement significantly. Reasons for
      the different performance of the two models are discussed. The quantum chemical
      data were used to discuss the microscopic basis of experimental enthalpy and
      entropy data, to determine the enthalpy and entropy contributions in chelate ring
      closure reactions and to discuss the origin of the so-called "chelate effect".
      Contrary to many earlier suggestions, this is not even in the gas phase, a result
      of changes in translation entropy contributions. There is no simple explanation
      of the high stability of chelate complexes; it is a result of both enthalpy and
      entropy contributions that vary from one system to the other.

PMID- 14640676
TI  - Abeta protofibrils possess a stable core structure resistant to hydrogen
      exchange.
AB  - Protofibrils are transient structures observed during in vitro formation of
      mature amyloid fibrils and have been implicated as the toxic species responsible
      for cell dysfunction and neuronal loss in Alzheimer's disease (AD) and other
      protein aggregation diseases. To better understand the roles of protofibrils in
      amyloid assembly and Alzheimer's disease, we characterized secondary structural
      features of these heterogeneous and metastable assembly intermediates. We
      chromatographically isolated different size populations of protofibrils from
      amyloid assembly reactions of Abeta(1-40), both wild type and the Arctic variant
      associated with early onset familial AD, and exposed them to hydrogen-deuterium
      exchange analysis monitored by mass spectrometry (HX-MS). We show that HX-MS can
      distinguish among unstructured monomer, protofibrils, and fibrils by their
      different protection patterns. We find that about 40% of the backbone amide
      hydrogens of Abeta protofibrils are highly resistant to exchange with deuterium
      even after 2 days of incubation in aqueous deuterated buffer, implying a very
      stable, presumably H-bonded, core structure. This is in contrast to mature
      amyloid fibrils, whose equally stable structure protects about 60% of the
      backbone amide hydrogens over the same time frame. We also find a surprising
      degree of specificity in amyloid assembly, in that wild type Abeta is
      preferentially excluded from both protofibrils and fibrils grown from an
      equimolar mixture of wild type and Arctic mutant peptides. These and other data
      are interpreted and discussed in terms of the role of protofibrils in fibril
      assembly and in disease.

PMID- 14640675
TI  - Mechanism of aromatic amino acid hydroxylation.

PMID- 14640677
TI  - Identification of the structural and functional boundaries of the multidrug
      resistance protein 1 cytoplasmic loop 3.
AB  - Multidrug resistance protein (MRP) 1 is a member of the ABCC branch of the ATP
      binding cassette (ABC) transporter superfamily that can confer resistance to
      natural product chemotherapeutic drugs and transport a variety of conjugated
      organic anions, as well as some unconjugated compounds in a glutathione- (GSH-)
      dependent manner. In addition to the two tandemly repeated polytopic membrane
      spanning domains (MSDs) typical of ABC transporters, MRP1 and its homologues
      MRP2, -3, -6, and -7 contain a third NH(2)-terminal MSD. The cytoplasmic loop
      (CL3) connecting this MSD, but apparently not the MSD itself, is required for
      MRP1 leukotriene C(4) (LTC(4)) transport activity, substrate binding and
      appropriate trafficking of the protein to the basolateral membrane. We have used
      a baculovirus dual-expression system to produce various functionally
      complementing fragments of MRP1 in insect Sf21 cells to precisely define the
      region in CL3 that is required for activity and substrate binding. Using a
      parallel approach in polarized MDCK-I cells, we have also defined the region of
      CL3 that is required for basolateral trafficking. The CL3 NH(2)- and COOH
      proximal functional boundaries have been identified as Cys(208) and Asn(260),
      respectively. Cys(208) also corresponds to the NH(2)-proximal boundary of the
      region required for basolateral trafficking in MDCK-I cells. However, additional
      residues downstream of the CL3 COOH-proximal functional boundary extending to
      Lys(270) were found to be important for basolateral localization. Finally, we
      show that regions in CL3 necessary for LTC(4) binding and transport are also
      required for binding of the photoactivatable GSH derivative azidophenacyl-GSH.

PMID- 14640678
TI  - Local destabilization of the tropomyosin coiled coil gives the molecular
      flexibility required for actin binding.
AB  - Tropomyosin, a coiled coil protein that binds along the length of actin
      filaments, contains 40 uninterrupted heptapeptide repeats characteristic of
      coiled coils. Yet, it is flexible. Regions of tropomyosin that may be important
      for binding to the filament and for interacting with troponin deviate from
      canonical coiled coil structure in subtle ways, altering the local conformation
      or energetics without interrupting the coiled coil. In a region rich in interface
      alanines (an Ala cluster), the chains pack closer than in canonical coiled coils,
      and are staggered, resulting in a bend [Brown et al. (2001) Proc. Natl. Acad.
      Sci. U.S.A. 98, 8496-8501]. Brown et al. suggested that bends at alanine clusters
      allow tropomyosin to wind on the actin filament helix. Another explanation is
      that local destabilization of the coiled coil, rather than close packing of the
      chains at Ala clusters per se, allows flexibility. Changing three Ala residues to
      canonical interface residues, A74L-A78V-A81L, greatly stabilized tropomyosin,
      measured using circular dichroism and differential scanning calorimetry, and
      reduced actin affinity >10-fold. Normal actin affinity and stability were
      restored in a mutant A74Q-A78N-A81Q that mimicked the stability of the Ala
      cluster but not the close packing of the chains. Analysis and modeling of
      comparable mutations introduced closer to the N-terminus show that the effects on
      stability and function depend on context. Models based on tropomyosin crystal
      structures give insight into possible effects of the mutations on the structure.
      We conclude that the significance of the Ala clusters in allowing flexibility of
      tropomyosin is stability-driven.

PMID- 14640679
TI  - Water-mediated hydrogen-bonded network on the cytoplasmic side of the Schiff base
      of the L photointermediate of bacteriorhodopsin.
AB  - The L intermediate in the proton-motive photocycle of bacteriorhodopsin is the
      starting state for the first proton transfer, from the Schiff base to Asp85, in
      the formation of the M intermediate. Previous FTIR studies of L have identified
      unique vibration bands caused by the perturbation of several polar amino acid
      side chains and several internal water molecules located on the cytoplasmic side
      of the retinylidene chromophore. In the present FTIR study we describe spectral
      features of the L intermediate in D(2)O in the frequency region which includes
      the N-D stretching vibrations of the backbone amides. We show that a broad band
      in the 2220-2080 cm(-1) region appears in L. By use of appropriate (15)N labeling
      and mutants, the lower frequency side of this band in L is assigned to the amides
      of Lys216 and Gly220. These amides are coupled to each other, and interact with
      Thr46 and Val49 in helix B and Asp96 in helix C via weakly H-bonding water
      molecules that exhibit O-D stretching vibrations at 2621 and 2605 cm(-1). These
      water molecules are part of a hydrogen-bonded network characteristic of L which
      includes other water molecules located closer to the chromophore that exhibit an
      O-D stretching vibration at 2589 cm(-1). This structure, extending from the
      Schiff base to the internal proton donor Asp96, stabilizes L and affects the L-to
      M transition.

PMID- 14640680
TI  - Structure-based design of an indolicidin peptide analogue with increased protease
      stability.
AB  - Indolicidin is an antimicrobial cationic peptide with broad-spectrum activity
      isolated from bovine neutrophils. An indolicidin analogue CP-11, ILKKWPWWPWRRK
      NH(2), with improved activity against Gram-negative bacteria had increased
      positive charge and amphipathicity while maintaining the short length of the
      parent molecule. The structure of CP-11 in the presence of dodecylphosphocholine
      (DPC) micelles was determined using nuclear magnetic resonance spectroscopy. CP
      11 was found to be an amphipathic molecule with a U-shaped backbone bringing the
      N- and C-termini in close proximity. On the basis of this close proximity, a
      cyclic disulfide-bonded peptide cycloCP-11, ICLKKWPWWPWRRCK-NH(2), was designed
      to stabilize the lipid-bound structure and to increase protease resistance. The
      three-dimensional structure of cycloCP-11 was determined under the same
      conditions as for the linear peptide and was found to be similar to CP-11. Both
      CP-11 and cycloCP-11 associated with phospholipid membranes in a similar manner
      as indicated by circular dichroism and fluorescence spectra. The minimal
      inhibitory concentrations of CP-11 and cycloCP-11 for a range of bacteria
      differed by no more than 2-fold, and they were nonhemolytic at concentrations up
      to 256 microg/mL. Cyclization was found to greatly increase protease stability.
      The half-life of cycloCP-11 in the presence of trypsin was increased by 4.5-fold
      from 4 to 18 min. More importantly, the antibacterial activity of cycloCP-11, but
      not that of CP-11, in the presence of trypsin was completely retained up to 90
      min since the major degradation product was equally active. A structural
      comparison of CP-11 and cycloCP-11 revealed that the higher trypsin resistance of
      cycloCP-11 may be due to the more compact packing of lysine and tryptophan side
      chains. These findings suggest that cyclization may serve as an important
      strategy in the rational design of antimicrobial peptides.

PMID- 14640681
TI  - Characterization of the yeast peroxiredoxin Ahp1 in its reduced active and
      overoxidized inactive forms using NMR.
AB  - Peroxiredoxins (Prx's) are a superfamily of thiol-specific antioxidant proteins
      present in all organisms and involved in the hydroperoxide detoxification of the
      cell. The catalytic cysteine of Prx's reduces hydroperoxides and is transformed
      into a transient sulfenic acid (Cys-SOH). At high hydroperoxide concentration,
      the sulfenic acid can be overoxidized into a sulfinate, or even a sulfonate. We
      present here the first peroxiredoxin characterization by solution NMR of the
      Saccharomyces cerevisiae alkylhydroperoxide reductase (Ahp1) in its reduced and
      in vitro overoxidized forms. NMR (15)N relaxation data and ultracentrifugation
      experiments indicate that the protein behaves principally as a homodimer (2 x 19
      kDa) in solution, regardless of the redox state. In vitro treatment of Ahp1 by a
      large excess of tBuOOH leads to an inactive form, with the catalytic cysteine
      overoxidized into sulfonate, as demonstrated by (13)C NMR. Depending on the amino
      acid sequence of their active site, Prx's are classified into five different
      families. In this classification, Ahp1 is a member of the scarcely studied D-type
      Prx's. Ahp1 is unique among the D-type Prx's in its ability to form an
      intermolecular disulfide. The peptidic sequence of Ahp1 was analyzed and compared
      to other D-type Prx sequences.

PMID- 14640682
TI  - Role of the fusion peptide and membrane-proximal domain in HIV-1 envelope
      glycoprotein-mediated membrane fusion.
AB  - The N-terminal fusion peptide and the interfacial sequence preceding the
      transmembrane anchor of HIV-1 gp41 are required for viral fusion. Studies with
      synthetic peptides indicated that these regions function by destabilizing
      membranes, which is regarded as a crucial step in the membrane fusion reaction.
      However, it is not clear whether membrane destabilization is induced by these
      sequences in the intact gp41. We address this question by examining fusion and
      destabilization of membranes expressing HIV-1(IIIB) wild-type Env and two mutant
      Envs. (1) A Glu residue at position 2 of the gp41 fusion peptide is substituted
      for Val (V2E) to produce one mutant. (2) Residues 665-682 in the membrane
      proximal domain are deleted to form the other. The process of membrane
      destabilization was monitored by the influx of Sytox, an impermeant fluorescent
      dye, into the Env-expressing cells following the interaction with CD4-CXCR4
      complexes, and fusion was monitored by observing dye transfer between Env
      expressing cells and appropriate target cells. We also monitored the
      conformational changes in the Envs following their interactions with CD4 and
      CXCR4 by immunofluorescence using an anti-gp41 mAb that reacts with the six-helix
      bundle. In contrast to the wild type, both Env mutants did not mediate cell
      fusion. The V2E Env did not mediate membrane destabilization. However, the Env
      with an unmodified fusion peptide but with a deletion of residues 665-682 in the
      membrane-proximal domain did mediate membrane destabilization. The wild type and
      both mutant Envs undergo conformational changes detected by the anti-gp41 six
      helix bundle mAbs. Our results suggest that in intact HIV-1 Env the membrane
      proximal domain is not required for membrane perturbations, but rather enables
      the bending of gp41 that is required for viral and target membranes to come
      together. Moreover, the observation that the Delta665-683 Env self-inserts its
      fusion peptide but does not cause fusion suggests that self-insertion of the
      fusion peptide is not sufficient for HIV-1 Env-mediated fusion.

PMID- 14640683
TI  - Charge transport in DNA duplex/quadruplex conjugates.
AB  - DNA conjugates containing adjacent duplex and guanine quadruplex assemblies have
      been designed to explore charge transport into quadruplex architectures. The
      quadruplex assemblies have been characterized structurally using circular
      dichroism and by assaying for chemical protection. Using an intercalating rhodium
      photooxidant, noncovalently bound or tethered to the duplex end, oxidizing
      radicals are found to be trapped in the folded quadruplex. Damage is observed
      almost exclusively at the external tetrads of the quadruplex. Little damage of
      the center tetrad is observed, due most likely to lowered efficiency of radical
      trapping within the quadruplex core. This pattern of damage is distinct from that
      observed for repetitive G sequences within duplex DNA. The data indicate,
      furthermore, that in the conjugates examined, the guanine quadruplex provides a
      more effective trap than a 5'-GG-3' guanine doublet within duplex DNA. Within
      these assemblies, sufficient base-base overlap must exist at the
      duplex/quadruplex junction to allow for charge migration. This funneling of
      damage to the quadruplex, as well as the unique pattern of damage within the
      quadruplex, requires consideration with respect to the analysis of oxidative DNA
      damage within the cell.

PMID- 14640684
TI  - Hydrogen bonding alteration of Thr-204 in the complex between pharaonis
      phoborhodopsin and its transducer protein.
AB  - Pharaonis phoborhodopsin (ppR, also called pharaonis sensory rhodopsin II, psRII)
      is a receptor for negative phototaxis in Natronobacterium pharaonis. It forms a
      2:2 complex with its transducer protein, pHtrII, in membranes and transmits light
      signals through the change in the protein-protein interaction. We previously
      found that the ppR(K) minus ppR spectrum in D(2)O possesses vibrational bands of
      ppR at 3479 (-)/3369 (+) cm(-1) only in the presence of pHtrII [Furutani, Y.,
      Sudo, Y., Kamo, N., and Kandori, H. (2003) Biochemistry 42, 4837-4842]. A D/H
      unexchangeable X-H group appears to form a stronger hydrogen bond upon retinal
      photoisomerization in the ppR-pHtrII complex. This article aims to identify the
      group by use of various mutant proteins. According to the crystal structure, Tyr
      199 of ppR forms a hydrogen bond with Asn-74 of pHtrII in the complex.
      Nevertheless, the 3479 (-)/3369 (+) cm(-1) bands were preserved in the Y199F
      mutant, excluding the possibility that the bands are O-H stretches of Tyr-199. On
      the other hand, Thr-204 and Tyr-174 form a hydrogen bond between the retinal
      chromophore pocket and the binding surface of the ppR-pHtrII complex. These FTIR
      measurements revealed that the bands at 3479 (-)/3369 (+) cm(-1) disappeared in
      the T204A mutant, while being shifted to 3498 (-) and 3474 (+) cm(-1) in the
      T204S mutant. They appear at 3430 (-)/3402 (+) cm(-1) in the Y174F mutant. From
      these results, we concluded that the bands at 3479 (-)/3369 (+) cm(-1) originate
      from the O-H stretch of Thr-204. A stronger hydrogen bond as shown by a large
      spectral downshift (110 cm(-1)) suggests that the specific hydrogen bonding
      alteration of Thr-204 takes place upon retinal photoisomerization, which does not
      occur in the absence of the transducer protein. Thr-204 has been known as an
      important residue for color tuning and photocycle kinetics in ppR. The results
      presented here point to an additional important role of Thr-204 in ppR for the
      interaction with pHtrII. Specific interaction in the complex that involves Thr
      204 presumably affects the decay kinetics and binding affinity in the M
      intermediate.

PMID- 14640685
TI  - Identification of important residues in metal-chelate recognition by monoclonal
      antibodies.
AB  - The molecular characterization of antibodies directed against metal-chelate
      complexes will provide important insights into the design and development of
      radiotherapeutic and radioimaging reagents. In this study, two monoclonal
      antibodies directed against different metal-chelate complexes were expressed as
      recombinant Fab fragments. Covalent modification and site-directed mutagenesis
      were employed to ascertain those residues important in antigen recognition.
      Antibody 5B2 was raised to a Pb(II)-loaded isothiocyanatobenzyl
      diethylenetriamine pentaacetic acid (DTPA)-protein conjugate. The native antibody
      bound to complexes of Pb(II)-p-aminobenzyl-DTPA with an affinity of 4.6 x 10(-9)
      M. A monovalent Fab fragment prepared from the native protein and a bivalent
      recombinant fragment exhibited comparable affinities for the same Pb(II)-chelate
      complex, approximately 6-fold lower than that of the intact antibody. Covalent
      modification and molecular modeling predicted that Lys(58) in the heavy chain
      contacted the Pb(II)-chelate ligand. Mutational analysis supported a role for
      Lys(58) in ion pair or hydrogen bond formation with the carboxylate groups on the
      chelate. Antibody E5 was directed toward an isothiocyanatobenzyl-ethylenediamine
      tetraacetic acid (EDTA)-protein conjugate loaded with ionic Cd(II). The native
      immunoglobulin recognized Cd(II)-p-aminobenzyl-EDTA with an affinity of 8.2 x 10(
      12) M. A proteolytically derived fragment and a bivalent recombinant fragment
      bound to the same Cd(II)-chelate complex with affinities that were comparable to
      that of the native antibody. Homology modeling and mutagenesis identified three
      residues (Trp(52) and His(96) in the heavy chain and Arg(96) in the light chain)
      that were important for Cd(II)-chelate recognition. His(96) likely mediates a
      direct ligation to the Cd(II) ion and Trp(52) appears to be involved in
      hydrophobic stacking with the benzyl moiety of the chelator. Arg(96) appeared to
      mediate an electrostatic or hydrogen bond to the chelate portion of the complex.
      These studies demonstrate that antibody recognition of metal-chelate haptens
      occurs through a limited number of molecular contacts and that these molecular
      interactions involve both direct ligation between the antibody and the metal ion
      and interactions between the antibody and the chelator.

PMID- 14640686
TI  - Thermodynamic stability and structural features of the J4/5 loop in a
      Pneumocystis carinii group I intron.
AB  - The J4/5 loop of the group I intron in the mouse-derived fungal pathogen
      Pneumocystis carinii is the docking site for the first step of the RNA-catalyzed
      self-splicing reaction and thus is a model of a potential drug target. This
      purine-rich asymmetric internal loop, 5'GGAAG/3'UAGU, is also thermodynamically
      more stable than other internal loops with two GU closing pairs and three
      nucleotides opposite two nucleotides. The results from optical melting, nuclear
      magnetic resonance spectroscopy, and functional group substitution experiments
      suggest that the GU closing pairs form and that sheared GA pairs form in the
      internal loop. The NMR spectra show evidence of conformational dynamics, and
      several GA pairings are possible. Thus, this dynamic loop presents several
      possible structures for potential binding of drugs that target group I self
      splicing introns. The results also contribute to understanding the structural and
      dynamic basis for the function and thermodynamic stability of this loop.

PMID- 14640688
TI  - Fidelity of DNA polymerase delta holoenzyme from Saccharomyces cerevisiae: the
      sliding clamp proliferating cell nuclear antigen decreases its fidelity.
AB  - DNA polymerases delta and epsilon (pol delta and epsilon) are the two major
      replicative polymerases in the budding yeast Saccharomyces cerevisiae. The
      fidelity of pol delta is influenced by its 3'-5' proofreading exonuclease
      activity, which corrects misinsertion errors, and by enzyme cofactors. PCNA is a
      pol delta cofactor, called the sliding clamp, which increases the processivity of
      pol delta holoenzyme. This study measures the fidelity of 3'-5' exonuclease
      proficient and -deficient pol delta holoenzyme using a synthetic 30mer
      primer/100mer template in the presence and absence of PCNA. Although PCNA
      increases pol delta processivity, the presence of PCNA decreased pol delta
      fidelity 2-7-fold. In particular, wild-type pol delta demonstrated the following
      nucleotide substitution efficiencies for mismatches in the absence of PCNA: G.G,
      0.728 x 10(-4); T.G, 1.82 x 10(-4); A.G, <0.01 x 10(-4). In the presence of PCNA
      these values increased as follows: G.G, 1.30 x 10(-4); T.G, 2.62 x 10(-4); A.G,
      0.074 x 10(-4). A similar but smaller effect was observed for exonuclease
      deficient pol delta (i.e., 2-4-fold increase in nucleotide substitution
      efficiencies in the presence of PCNA). Thus, the fidelity of wild-type pol delta
      in the presence of PCNA is more than 2 orders of magnitude lower than the
      fidelity of wild-type pol epsilon holoenzyme and is comparable to the fidelity of
      exonuclease-deficient pol epsilon holoenzyme.

PMID- 14640687
TI  - Efficiency of extension of mismatched primer termini across from cisplatin and
      oxaliplatin adducts by human DNA polymerases beta and eta in vitro.
AB  - DNA polymerases beta and eta are among the few eukaryotic polymerases known to
      efficiently bypass cisplatin and oxaliplatin adducts in vitro. Our laboratory has
      previously established that both polymerases misincorporated dTTP with high
      frequency across from cisplatin- and oxaliplatin-GG adducts. This decrease in
      polymerase fidelity on platinum-damaged DNA could lead to in vivo mutations, if
      this base substitution were efficiently elongated. In this study, we performed a
      steady-state kinetic analysis of the steps required for fixation of dTTP
      misinsertion during translesion synthesis past cisplatin- and oxaliplatin-GG
      adducts by pol beta and pol eta. The efficiency of translesion synthesis by pol
      eta past Pt-GG adducts was very similar to that observed for this polymerase when
      the template contains thymine-thymine dimers. This finding suggested that pol eta
      could play a role in translesion synthesis past platinum-GG adducts in vivo. On
      the other hand, translesion synthesis past platinum-GG adducts by pol beta was
      much less efficient. Translesion synthesis by pol eta is likely to be
      predominantly error-free, since the probability of correct insertion and
      extension by pol eta was 1000-2000-fold greater than the probability of incorrect
      insertion and extension. Our results also indicated that for pol eta the
      frequency of misincorporation is the same across from the 3'G and the 5'G of the
      platinum-GG adducts for both cisplatin and oxaliplatin adducts. On the other
      hand, pol beta is more likely to misinsert at the 3'G of the adducts and
      misinsertion occurs at higher frequency for oxaliplatin-GG than for cisplatin-GG
      adducts.

PMID- 14640689
TI  - Spectroscopic determination of the binding affinity of zinc to the DNA-binding
      domains of nuclear hormone receptors.
AB  - Zinc binding to the two Cys(4) sites present in the DNA-binding domain (DBD) of
      nuclear hormone receptor proteins is required for proper folding of the domain
      and for protein activity. By utilizing Co(2+) as a spectroscopic probe, we have
      characterized the metal-binding properties of the two Cys(4) structural zinc
      binding sites found in the DBD of human estrogen receptor alpha (hERalpha-DBD)
      and rat glucocorticoid receptor (GR-DBD). The binding affinity of Co(2+) to the
      two proteins was determined relative to the binding affinity of Co(2+) to the
      zinc finger consensus peptide, CP-1. Using the known dissociation constant of
      Co(2+) from CP-1, the dissociation constants of cobalt from hERalpha-DBD were
      calculated: K(d1)(Co) = 2.2 (+/- 1.0) x 10(-7) M and K(d2)(Co) = 6.1 (+/- 1.5) x
      10(-7) M. Similarly, the dissociation constants of Co(2+) from GR-DBD were
      calculated: K(d1)(Co) = 4.1 (+/- 0.6) x 10(-7) M and K(d2)(Co) = 1.7 (+/- 0.3) x
      10(-7) M. Metal-binding studies conducted in which Zn(2+) displaces Co(2+) from
      the metal-binding sites of hERalpha-DBD and GR-DBD indicate that Zn(2+) binds to
      each of the Cys(4) metal-binding sites approximately 3 orders of magnitude more
      tightly than Co(2+) does: the stoichiometric dissociation constants are K(d1)(Zn)
      = 1 (+/- 1) x 10(-10) M and K(d2)(Zn) = 5 (+/- 1) x 10(-10) M for hERalpha-DBD
      and K(d1)(Zn) = 2 (+/- 1) x 10(-10) M and K(d2)(Zn) = 3 (+/- 1) x 10(-10) M for
      GR-DBD. These affinities are comparable to those observed for most other
      naturally occurring structural zinc-binding sites. In contrast to the recent
      prediction by Low et. al. that zinc binding in these systems should be
      cooperative [Low, L. Y., Hernandez, H., Robinson, C. V., O'Brien, R., Grossmann,
      J. G., Ladbury, J. E., and Luisi, B. (2002) J. Mol. Biol. 319, 87-106], these
      data suggest that the zincs that bind to the two sites in the DBDs of hERalpha
      DBD and GR-DBD do not interact.

PMID- 14640690
TI  - Effects of site-directed mutations on heme reduction in Escherichia coli nitrate
      reductase A by menaquinol: a stopped-flow study.
AB  - We have studied the effects of site-directed mutations in Escherichia coli
      nitrate reductase A (NarGHI) on heme reduction by a menaquinol analogue
      (menadiol) using the stopped-flow method. For NarGHI(H66Y) and NarGHI(H187Y),
      both lacking heme b(L) but having heme b(H), the heme reduction by menadiol is
      abolished. For NarGHI(H56R) and NarGHI(H205Y), both without heme b(H) but with
      heme b(L), a smaller and slower heme reduction compared to that of the wild-type
      enzyme is observed. These results indicate that electrons from menadiol oxidation
      are transferred initially to heme b(L). A transient species, likely to be
      associated with a semiquinone radical anion, was generated not only on reduction
      of the wild-type enzyme as observed previously (1) but also on reduction of
      NarGHI(H56R) and NarGHI(H205Y). The inhibitors 2-n-heptyl-4-hydroxyquinoline-N
      oxide and stigmatellin both have significant effects on the reduction kinetics of
      NarGHI(H56R) and NarGHI(H205Y). We have also investigated the reoxidation of
      menadiol-reduced heme by nitrate in the mutants. Compared to the wild type, no
      significant heme reoxidation is observed for NarGHI(H56R) and NarGHI(H205Y). This
      result indicates that a single mutation removing heme b(H) blocks the electron
      transfer pathway from the subunit NarI to the catalytic dimer NarGH.

PMID- 14640691
TI  - Temperature-induced dissociation of protein aggregates: accessing the denatured
      state.
AB  - The thermal denaturation of lysozyme and ribonuclease A (RNase A) under reducing
      and nonreducing conditions at neutral pH has been monitored by Fourier transform
      infrared spectroscopy. In the absence of the reductant, lysozyme and RNase A
      undergo apparent three- and two-state denaturation, respectively, as observed
      from the conformation-sensitive amide I' band. For both proteins the hydrogen
      deuterium exchange takes place at lower temperatures than the main denaturation
      temperatures, suggesting that a transient denaturation mechanism occurs. The
      observed transition at 51.2 degrees C during the denaturation of lysozyme is
      attributed to this transient effect, rather than to the loss of tertiary
      structure. Under reducing conditions lysozyme aggregates during the heating
      phase, whereas RNase A shows only a minor aggregation, which further increases
      during the cooling step. The reduced stability of both proteins can be correlated
      with the transient denaturation behavior, which is also suggested to be involved
      in protein aggregation at physiologically relevant temperatures. In addition, it
      is shown that when the temperature is further increased, the amorphous aggregates
      dissociate. Comparison of the dissociated states with the denatured states
      obtained under nonreducing conditions indicates that these states have the same
      conformation. By using a two-dimensional correlation analysis we were able to
      show that the dissociation is preceded by a conformational change. It is argued
      that this extends to other types of perturbation.

PMID- 14640692
TI  - Structure and function of the middle domain of ClpB from Escherichia coli.
AB  - ClpB belongs to the Hsp100/Clp ATPase family. Whereas a homologue of ClpB, ClpA,
      interacts with and stimulates the peptidase ClpP, ClpB does not associate with
      peptidases and instead cooperates with DnaK/DnaJ/GrpE in an efficient
      reactivation of severely aggregated proteins. The major difference between ClpA
      and ClpB is located in the middle sequence region (MD) that is much longer in
      ClpB than in ClpA and contains several segments of coiled-coil-like heptad
      repeats. The function of MD is unknown. We purified the isolated MD fragment of
      ClpB from Escherichia coli (residues 410-570). Circular dichroism (CD) detected a
      high population of alpha-helical structure in MD. Temperature-induced changes in
      CD showed that MD is a thermodynamically stable folding domain. Sedimentation
      equilibrium showed that MD is monomeric in solution. We produced four truncated
      variants of ClpB with deletions of the following heptad-repeat-containing regions
      in MD: 417-455, 456-498, 496-530, and 531-569. We found that the removal of each
      heptad-repeat region within MD strongly inhibited the oligomerization of ClpB,
      which produced low ATPase activity of the truncated ClpB variants as well as
      their low chaperone activity in vivo. Only one ClpB variant (Delta417-455) could
      partially complement the growth defect of the clpB-null E. coli strain at 50
      degrees C. Our results show that heptad repeats in MD play an important role in
      stabilization of the active oligomeric form of ClpB. The heptad repeats are
      likely involved in stabilization of an intra-MD helical bundle rather than an
      intersubunit coiled coil.

PMID- 14640693
TI  - Molecular heterogeneity of a type III cytotoxin, Pseudomonas aeruginosa exoenzyme
      S.
AB  - Pseudomonas aeruginosa ExoS is a bifunctional type III cytotoxin. The N-terminus
      (residues 1-232) is a Rho GTPase activating protein (GAP) domain, while the C
      terminus (residues 233-453) is a FAS-dependent ADP-ribosyltransferase domain that
      targets Ras and Ras-like GTPases. A membrane localization domain (residues 51-72)
      localizes ExoS to a perinuclear region within eukaryotic cells. Recent studies
      observed that ExoS is auto-ADP-ribosylated upon delivery into eukaryotic cells.
      Auto-ADP-ribosylated ExoS analyzed from eukaryotic cells displayed pI
      heterogeneity and prompted an analysis of this heterogeneity. Bacterial
      associated ExoS and ExoS that had been secreted by P. aeruginosa also showed pI
      heterogeneity with five charge forms ranging in pI from 5.1 to 5.9. The pI
      heterogeneity of ExoS was independent of a mass change and thus represented
      molecular charge conformers. Urea was not required to observe the pI conformers
      of ExoS; it enhanced the resolution and formation of pI conformers during the
      focusing component of the analysis. ExoS(E381D), a mutant deficient in ADP
      ribosyltransferase activity, isolated from cultured cells showed charge forms
      that migrated to a more acidic pI than type III secreted ExoS but more basic than
      auto-ADP-ribosylated ExoS. Incubation of cell lysates with Mn(2+) shifted the pI
      of ExoS(E381D) to a pI identical to secreted ExoS. This indicates that within the
      mammalian cells ExoS undergoes a negatively charged modification, in addition to
      auto-ADP-ribosylation observed for wild-type ExoS. ExoT, ExoU, and YopE also
      focus into multiple pI forms, suggesting that this is a common property of type
      III cytotoxins.

PMID- 14640694
TI  - Mts1 regulates the assembly of nonmuscle myosin-IIA.
AB  - The formation of myosin-II filaments is fundamental to contractile and motile
      processes in nonmuscle cells, and elucidating the mechanisms controlling filament
      assembly is essential for understanding how myosin-II rapidly responds to
      changing conditions within the cell. Several proteins including KRP and a novel
      38 kDa protein (1, 2) have been shown to modulate filament assembly through the
      stabilization of myosin-II assemblies. In contrast, we demonstrate that mts1, a
      member of the Ca(2+)-regulated S100 family of proteins, may regulate the
      monomeric, unassembled state in an isoform-specific manner. Biochemical analyses
      demonstrate that mts1 has a 9-fold higher affinity for myosin-IIA filaments than
      for myosin-IIB filaments. At stoichiometric levels, mts1 inhibits the assembly of
      myosin-IIA monomers into filaments and promotes the disassembly of myosin-IIA
      filaments into monomers; however, mts1 has little effect on the assembly
      properties of myosin-IIB. Using a solution based-assay, we have demonstrated that
      mts1 binds to residues 1909-1924 of the myosin-IIA heavy chain, which is near the
      C-terminal tip of the alpha-helical coiled-coil. The observation that mts1 binds
      a linear sequence of approximately 16 amino acids is consistent with other S100
      family members, which bind linear sequences of 13-22 residues in their protein
      targets. In addition, mts1 increases the critical monomer concentration for
      myosin-IIA filament assembly by approximately 11-fold. Kinetic assembly assays
      indicate that the elongation rate and the extent of polymerization depend on the
      initial myosin-IIA concentration; however, mts1 had only a small affect on the
      half-time for assembly and predominately affected the extent of myosin IIA
      polymerization. Altogether, these observations are consistent with mts1
      regulating myosin IIA assembly by monomer sequestration and suggest that mts1
      regulates cell shape and motility through the modulation of myosin-IIA function.

PMID- 14640695
TI  - Steroid structural requirements for stabilizing or disrupting lipid domains.
AB  - In artificial membrane bilayers, saturated long acyl chain-containing
      phospholipids and cholesterol (Chol) interact to form more ordered domains than
      those in phospholipids with unsaturated or short fatty acyl chains. We have
      extended the fluorescence techniques of London et al. [Xu, X., and London, E.
      (2000) Biochemistry 39, 843-849; Xu, X., Bittman, R., Duportail, G., Heissler,
      D., Vilchezes, C., and London, E. (2001) J. Biol. Chem. 276, 33540-33546] to
      study the propensity of several steroids to form or disrupt such ordered lipid
      domains. Temperature-dependent fluorescence quenching and steady-state
      polarization of the extrinsic fluorescent probe diphenylhexatriene (DPH) in model
      membranes composed of dipalmitoylphosphatidylcholine (or sphingomyelin), a
      nitroxide spin-labeled phosphatidylcholine (12-SLPC), and a given steroid were
      combined to study the influence of the latter on (a) ordered lipid domain
      formation, (b) stabilization, and (c) the extension of the ordered lipid
      assemblies. The results of the two totally independent methods, fluorescence
      quenching by 12-SLPC and fluorescence polarization of DPH, show that all steroids
      examined, except for Chol and 25-hydroycholesterol, behave as lipid domain
      disrupting compounds. Additionally, we found a positive correlation between the
      hydrophobicity of steroids and their ordered lipid domain-promoting activity.
      Comparison of the chemical structures disclosed some distinctive traits of
      ordered lipid domain-promoting steroids: (i) the presence of an isooctyl side
      chain bond at C17; (ii) the absence of carbons attached to C23 (i.e., C24-C27) in
      any of the other (domain-disrupting) steroids; (iii) the presence of a small
      polar group at position C3; and (iv) the absence of polar groups in the fused
      rings, with the exception of substitutions at position C3 in the A ring.

PMID- 14640696
TI  - Dissection of photodamage at low temperature and repair in darkness suggests the
      existence of an intermediate form of photodamaged photosystem II.
AB  - Irradiation of the photosynthetic machinery with strong light induces damage to
      the photosystem II complex (PSII), and this phenomenon is referred to as
      photodamage. In an attempt to characterize the mechanism of photodamage to PSII,
      we examined the events associated with photodamage by monitoring the phenomenon
      in Synechocystis sp. PCC 6803 at a low temperature. After the activity of PSII
      had been reduced to 10% of the original activity by exposure of Synechocystis
      cells to strong light at 10 degrees C, recovery was allowed to proceed at 34
      degrees C in darkness. Under these conditions, approximately 50% of the activity
      of PSII was restored within 60 min. The recovery in darkness did not require
      protein synthesis, as demonstrated by Western blotting analysis and a
      radiolabeling experiment with [(35)S]methionine. We also observed a similar
      recovery of PSII in darkness in isolated thylakoid membranes. Our findings,
      together with those of other studies, suggest the presence of an intermediate
      form of photodamaged PSII that is generated prior to the formation of
      photodamaged PSII.

PMID- 14640697
TI  - Broad substrate specificity of human cytochrome P450 46A1 which initiates
      cholesterol degradation in the brain.
AB  - The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of
      cholesterol. This reaction produces biologically active oxysterol, 24(S)
      hydroxycholesterol, and is also the first step in enzymatic degradation of
      cholesterol in the brain. We report here that P450 46A1 can further metabolize
      24(S)-hydroxycholesterol, giving 24,25- and 24,27-dihydroxycholesterols in both
      the cell cultures transfected with P450 46A1 cDNA and the in vitro reconstituted
      system with recombinant enzyme. In addition, P450 46A1 was able to carry out side
      chain hydroxylations of two endogenous C27-steroids with and without a double
      bond between C5-C6 (7alpha-hydroxycholesterol and cholestanol, respectively) and
      introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones
      with the C4-C5 double bond (progesterone and testosterone). Also, P450 46A1 was
      found to metabolize xenobiotics carrying out dextromethorphan O- and N
      demethylations, diclofenac 4'-hydroxylation, and phenacetin O-deethylation. Thus,
      substrate specificities of P450 46A1 are not limited to cholesterol and include a
      number of structurally diverse compounds. Activities of P450 46A1 suggest that,
      in addition to the involvement in cholesterol homeostasis in the brain, this
      enzyme may participate in metabolism of neurosteroids and drugs that can cross
      the blood-brain barrier and are targeted to the central nervous system.

PMID- 14640698
TI  - Epitope mapping of antigenic MUC1 peptides to breast cancer antibody fragment
      B27.29: a heteronuclear NMR study.
AB  - MUC1 mucin is a breast cancer-associated transmembrane glycoprotein, of which the
      extracellular domain is formed by the repeating 20-amino acid sequence
      GVTSAPDTRPAPGSTAPPAH. In neoplastic breast tissue, the highly immunogenic
      sequence PDTRPAP (in bold above) is exposed. Antibodies raised directly against
      MUC1-expressing tumors offer unique access to this neoplastic state, as they
      represent immunologically relevant "reverse templates" of the tumor-associated
      mucin. In a previous study [Grinstead, J. S., et al. (2002) Biochemistry 41, 9946
      9961], (1)H NMR methods were used to correlate the effects of cryptic
      glycosylation outside of the PDTRPAP core epitope sequence on the recognition and
      binding of Mab B27.29, a monoclonal antibody raised against breast tumor cells.
      In the study presented here, isotope-edited NMR methods, including (15)N and
      (13)C relaxation measurements, were used to probe the recognition and binding of
      the PDTRPAP epitope sequence to Fab B27.29. Two peptides were studied: a one
      repeat MUC1 16mer peptide of the sequence GVTSAPDTRPAPGSTA and a two-repeat MUC1
      40mer peptide of the sequence (VTSAPDTRPAPGSTAPPAHG)(2). (15)N and (13)C NMR
      relaxation parameters were measured for both peptides free in solution and bound
      to Fab B27.29. The (13)C(alpha) T(1) values best represent changes in the local
      correlation time of the peptide epitope upon binding antibody, and demonstrate
      that the PDTRPAP sequence is immobilized in the antibody-combining site. This
      result is also reflected in the appearance of the (15)N- and (13)C-edited HSQC
      spectra, where line broadening of the same peptide epitope resonances is
      observed. The PDTRPAP peptide epitope expands upon the peptide epitope identified
      previously in our group as PDTRP by homonuclear NMR experiments [Grinstead, J.
      S., et al. (2002) Biochemistry 41, 9946-9961], and illustrates the usefulness of
      the heteronuclear NMR experiments. The implications of these results are
      discussed within the context of MUC1 breast cancer vaccine design.

PMID- 14640699
TI  - Lipid-protein interactions studied by introduction of a tryptophan residue: the
      mechanosensitive channel MscL.
AB  - Trp fluorescence spectroscopy is a powerful tool to study the structures of
      membrane proteins and their interactions with the surrounding lipid bilayer. Many
      membrane proteins contain more than one Trp residue, making analysis of the
      fluorescence data more complex. The mechanosensitive channels MscL's of
      Mycobacterium tuberculosis (TbMscL) and Escherichia coli (EcMscL) contain no Trp
      residues. We have therefore introduced single Trp residues into the transmembrane
      regions of TbMscL and EcMscL to give the Trp-containing mutants F80W-TbMscL and
      F93W-EcMscL, respectively, which we show are highly suitable for measurements of
      lipid binding constants. In vivo cell viability assays in E. coli show that
      introduction of the Trp residues does not block function of the channels. The Trp
      containing mutants have been reconstituted into lipid bilayers by mixing in
      cholate followed by dilution to re-form membranes. Cross-linking experiments
      suggest that the proteins retain their pentameric structures in
      phosphatidylcholines with chain lengths between C14 and C24, phosphatidylserines,
      and phosphatidic acid. Quenching of Trp fluorescence by brominated phospholipids
      suggests that the Trp residue in F80W-TbMscL is more exposed to the lipid bilayer
      than the Trp residue in F93W-EcMscL. Binding constants for phosphatidylcholines
      change with changing fatty acyl chain length, the strongest interaction for both
      TbMscL and EcMscL being observed with a chain of length C16, corresponding to a
      bilayer of hydrophobic thickness ca. 24 A, compared to a hydrophobic thickness
      for TbMscL of about 26 A estimated from the crystal structure. Lipid binding
      constants change by only a factor of 1.5 in the chain length range from C12 to
      C24, much less than expected from theories of hydrophobic mismatch in which the
      protein is treated as a rigid body. It is concluded that MscL distorts to match
      changes in bilayer thickness. The binding constants for
      dioleoylphosphatidylethanolamine for both TbMscL and EcMscL relative to those for
      dioleoylphosphatidylcholine are close to 1. Quenching experiments suggest a
      single class of binding sites for phosphatidylserine, phosphatidylglycerol, and
      cardiolipin on TbMscL; binding constants are greater than those for
      phosphatidylcholine and decrease with increasing ionic strength, suggesting that
      charge interactions are important in binding these anionic phospholipids.
      Quenching experiments suggest two classes of lipid binding sites on TbMscL for
      phosphatidic acid, binding of phosphatidic acid being much less dependent on
      ionic strength than binding of phosphatidylserine.

PMID- 14640700
TI  - DNA damage and cytotoxicity induced by minor groove binding methyl sulfonate
      esters.
AB  - Minor groove specific DNA equilibrium binding peptides (lex) based on N
      methylpyrrole-carboxamide and/or N-methylimidazolecarboxamide subunits have been
      modified with an O-methyl sulfonate ester functionality to target DNA methylation
      in the minor groove at Ade/Thy- and/or Gua/Cyt-rich sequences. HPLC and
      sequencing gel analyses show that the Me-lex compounds all selectively react with
      DNA to afford N3-alkyladenine as a major adduct. The formation of the N3
      alkyladenine lesions is sequence-dependent based on the equilibrium binding
      preferences of the different lex peptides. In addition to the reaction at
      adenine, the molecules designed to target Gua/Cyt sequences also generate lesions
      at guanine; however, the methylation is not sequence dependent and takes places
      in the major groove at the N7-position. To determine if and how the level of the
      different DNA adducts and the sequence selectivity for their formation affects
      cytotoxicity, the Me-lex analogues were tested in wild type Escherichia coli and
      in mutant strains defective in base excision repair (tag and/or alkA or apn). The
      results demonstrate the importance of 3-methyladenine, and in some cases 3
      methylguanine, lesions in cellular toxicity, and the dominant protective role of
      the DNA glycosylases. There is no evidence that the sequence specificity is
      related to toxicity.

PMID- 14640701
TI  - Degradation of beta-amyloid by proteolytic antibody light chains.
AB  - Deposition of beta-amyloid (Abeta) is considered an important early event in the
      pathogenesis of Alzheimer's disease (AD). Clearance of Abeta thus represents a
      potential therapeutic approach. Antibody-mediated clearance of Abeta by
      vaccination inhibited and cleared Abeta deposition in animal models; however,
      inflammatory side effects were observed in humans. An alternative potentially
      noninflammatory approach to facilitate clearance is to proteolytically cleave
      Abeta. We screened 12 proteolytic recombinant antibody fragments for potential
      alpha-secretase activity, a naturally occurring enzyme that cleaves between the
      Lys16 and Leu17 residues of the amyloid precursor protein (APP). We utilized the
      synthetic alpha-secretase substrate, benzyloxycarbonyl-l-lysine o-nitrophenyl
      ester (Z-lys-o-Np) as a preliminary screen for alpha-secretase activity. Two
      antibody light chain fragments that hydrolyzed Z-lys-o-Np were identified. Abeta
      hydrolysis was studied using mass spectrometry to identify the cleavage patterns
      of the antibodies. The recombinant antibody light chain antibody fragment, c23.5,
      showed alpha-secretase-like activity, producing the 1-16 and 17-40 amino acid
      fragments of Abeta. The second light chain antibody fragment, hk14, demonstrated
      carboxypeptidase-like activity, cleaving sequentially from the carboxyl terminal
      of Abeta. These antibody light chains provide a novel route toward engineering
      efficient therapeutic antibodies capable of cleaving Abeta in vivo.

PMID- 14640702
TI  - Cbl PYXXM motifs activate the P85 subunit of phosphatidylinositol 3-kinase, Crk,
      atypical protein kinase C, and glucose transport during thiazolidinedione action
      in 3T3/L1 and human adipocytes.
AB  - The thiazolidinedione (TZD), rosiglitazone, has previously been found to tyrosine
      phosphorylate Cbl and activate Cbl-dependent phosphatidylinositol (PI) 3-kinase
      and atypical protein kinase Cs (aPKCs) while stimulating glucose transport in
      3T3/L1 adipocytes. Presently, the role of Cbl in rosiglitazone action was further
      assessed in both 3T3/L1 and human adipocytes by expressing Y371F and/or Y731F
      mutant forms of Cbl that nullified the functionality of canonical pYXXM motifs in
      Cbl. These mutants diminished the interaction of Cbl with the p85 subunit of PI 3
      kinase and inhibited subsequent increases in Cbl-dependent PI 3-kinase activity,
      aPKC activity, and glucose transport. These mutants also inhibited the
      interaction of Cbl with Crk, which has been implicated in the activation of other
      PI 3-kinase-independent signaling factors that have been found to be required
      during activation of glucose transport by insulin and other agonists. We conclude
      that pYXXM motifs in Cbl serve to activate PI 3-kinase-dependent and possibly PI
      3-kinase-independent pathways that are required for TZD-dependent glucose
      transport in adipocytes.

PMID- 14640704
TI  - Application of a molecularly imprinted polymer for the effective recognition of
      different anti-epidermal growth factor receptor inhibitors.
AB  - A molecularly imprinted polymer (MIP) was prepared using (E)-piceatannol, a
      natural potential anti-epidermal growth factor receptor (EGFR) inhibitor, as the
      template and 4-vinylpyridine as the functional monomer. The template was isolated
      from a Chinese traditional Tibetan medicinal herb, Caragana jubata, by a solid
      phase extraction procedure. The crude extract of this herb was loaded on the MIP
      column for the binding test, and two different compounds besides the template
      itself were specifically recognized by the polymer, which were identified to be
      butein and quercetin possessing potent anti-EGFR tyrosine kinase activities with
      IC(50) values of 10 and 15 microM, respectively. Affinity and selectivity for
      these inhibitors and another three compounds coexisting with the template in this
      herb were evaluated in the chromatographic mode. For the first time, the affinity
      of a molecularly imprinted polymer was investigated to be correlative to the
      bioactivities of the analytes. The chromatographic behavior of the analytes was
      consistent with their activity values: the more active inhibitor was retained
      longer on the MIP. This research work afforded us a new approach for the
      effective recognition of novel anti-EGFR inhibitors from herbs by using the MIP
      as the receptor mimic to assay the bioactivities of reserved components, which
      will be very helpful in the direct separation of lead candidates for anticancer
      drugs.

PMID- 14640703
TI  - 6-Deoxyerythronolide B analogue production in Escherichia coli through metabolic
      pathway engineering.
AB  - The erythromycin precursor polyketide 6-deoxyerythronolide B (6-dEB) is produced
      from one propionyl-CoA starter unit and six (2S)-methylmalonyl-CoA extender
      units. In vitro studies have previously demonstrated that the loading module of 6
      deoxyerythronolide B synthase (DEBS) exhibits relaxed substrate specificity and
      is able to accept butyryl-CoA, leading to the production of polyketides with
      butyrate starter units. We have shown that we can produce butyryl-CoA at levels
      of up to 50% of the total CoA pool in Escherichia coli cells that overexpress the
      acetoacetyl-CoA:acetyl-CoA transferase, AtoAD (EC 2.8.3.8), in media supplemented
      with butyrate. The DEBS polyketide synthase (PKS) used butyryl-CoA and
      methylmalonyl-CoA supplied in vivo by the AtoAD and methylmalonyl-CoA mutase
      pathways, respectively, to produce 15-methyl-6-dEB. Priming DEBS with endogenous
      butyryl-CoA affords an alternative and more direct route to 15-Me-6-dEB than that
      provided by the chemobiosynthesis method [Jacobsen, J. R., et al. (1997) Science
      277, 367-369], which relies on priming a mutant DEBS with an exogenously fed
      diketide thioester. The approach described here demonstrates the utility of
      metabolic engineering in E. coli to introduce precursor pathways for the
      production of novel polyketides.

PMID- 14640705
TI  - Frontal affinity chromatography combined on-line with mass spectrometry: a tool
      for the binding study of different epidermal growth factor receptor inhibitors.
AB  - Frontal affinity chromatography (FAC) is a simple but powerful method to analyze
      molecular interactions between an analyte and an immobilized ligand by
      calculating the extent of retardation of the elution front. By combination of FAC
      with a PE-Mariner electrospray ionization mass spectrometry, a very efficient and
      straightforward procedure was developed herein for analyzing the binding
      properties of different inhibitors of the epidermal growth factor receptor
      (EGFR). In this study, a polyclonal antibody prepared with a known anti-EGFR
      inhibitor coupled with bovine serum albumin was adopted as the stationary phase
      in the FAC system. Using the antibody to mimic the receptor, other different anti
      EGFR inhibitors as well as the small-molecule half-antigen itself were recognized
      directly from the crude extract of herb, which afforded us a novel promising
      approach for the efficient screening of lead compounds or drug candidates from
      natural resources.

PMID- 14640707
TI  - Structural characterization and detection of kale flavonoids by electrospray
      ionization mass spectrometry.
AB  - Sensitive and precise analytical methods are needed for flavonols, a subclass of
      flavonoids that has strong antioxidant activity. We report an improved method for
      identifying the predominant flavonols, quercetin and kaempferol, by collisionally
      activated dissociation (CAD) and quantifying them by high-performance liquid
      chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS) in the
      selected ion monitoring mode. Practical applications of the method were
      demonstrated using several kale and biological samples. Two commercial kale
      samples were found to have 77 or 244 ppm quercetin and 235 or 347 ppm kaempferol
      (ppm = microg of quercetin/g of kale or microg of kaempferol/g of kale by fresh
      weight, 5-15% relative standard deviation). Blanching was found to reduce the
      flavonols to approximately 60% of the levels found in the unblanched kale.
      Isotopically labeled kale (cultivar Vates) grown in a greenhouse under an
      atmosphere of (13)CO(2) was found to have much lower flavonol levels. UV-A and UV
      B supplementation during kale growth in the greenhouse was found to enhance both
      quercetin and kaempferol levels in Vates kale. The UV-B-supplemented kale not
      only produced more flavonols but the quercetin-to-kaempferol ratio was also
      higher than the UV-A-supplemented or the nonsupplemented kale. Recovery of
      flavonols from kale was approximately 60% based on spike and recovery trials with
      rutin, a glycoside of quercetin. Recovery of flavonols from biological samples
      spiked with rutin ranged from 96% for urine to 70% for plasma. Compared to UV
      detection, ESI-MS in the deprotonation mode provided lower detection limits, and
      both higher sensitivity and selectivity, in addition to structural
      characterization of the kale flavonols by CAD.

PMID- 14640711
TI  - Chip-based P450 drug metabolism coupled to electrospray ionization-mass
      spectrometry detection.
AB  - A chip-based P450 in vitro metabolism assay coupled with ESI-MS and ESI-MS/MS
      detection is described in this paper. The chips were made of a cyclic olefin
      polymer using a hot embossing process. The introduction of reagent solutions into
      the chip was carried out using fused-silica capillaries coupled to two syringes
      with the flow rate controlled by a syringe pump. Initial experiments described
      here employed a small commercial guard column in an off-chip format to desalt and
      concentrate the products of the enzymatic reaction prior to ESI-MS analysis. The
      system was used both to yield the Michaelis constant (K(m)) of the P450
      biotransformation of imipramine into desipramine and to determine the IC50 value
      of a chemical inhibitor (tranylcypromine) for this CYP2C19-mediated reaction. The
      results demonstrated that the kinetics of the reaction inside the 4-microL volume
      within the channels of the cyclic olefin polymer chip provided results in
      agreement with those reported in the literature using conventional assays. The
      above reactions were carried out using human liver microsomes, and the
      metabolites were detected by ESI-MS showing the potential of the chip-based P450
      reaction for metabolite screening studies as well as for P450 inhibition assays.
      A porous monolithic column was subsequently integrated into the chip to perform
      the reaction mixture cleanup process in an integrated fashion on the chip that is
      necessary for ESI-MS detection. The miniature monolithic SPE column was prepared
      in situ inside the chip via UV-initiated polymerization. The results obtained
      using the integrated system demonstrated the possibility of performing P450
      enzymatic reactions in a microvolume reaction chamber coupled directly to ESI-MS
      detection and required less than 4 microg of HLM protein.

PMID- 14640709
TI  - GutenTag: high-throughput sequence tagging via an empirically derived
      fragmentation model.
AB  - Shotgun proteomics is a powerful tool for identifying the protein content of
      complex mixtures via liquid chromatography and tandem mass spectrometry. The most
      widely used class of algorithms for analyzing mass spectra of peptides has been
      database search software such as SEQUEST. A new sequence tag database search
      algorithm, called GutenTag, makes it possible to identify peptides with unknown
      posttranslational modifications or sequence variations. This software automates
      the process of inferring partial sequence "tags" directly from the spectrum and
      efficiently examines a sequence database for peptides that match these tags. When
      multiple candidate sequences result from the database search, the software
      evaluates which is the best match by a rapid examination of spectral fragment
      ions. We compare GutenTag's accuracy to that of SEQUEST on a defined protein
      mixture, showing that both modified and unmodified peptides can be successfully
      identified by this approach. GutenTag analyzed 33,000 spectra from a human lens
      sample, identifying peptides that were missed in prior SEQUEST analysis due to
      sequence polymorphisms and posttranslational modifications. The software is
      available under license; visit http://fields.scripps.edu for information.

PMID- 14640712
TI  - Affinity capture of specific DNA-binding proteins for mass spectrometric
      identification.
AB  - We describe a general approach for affinity microcapture of site-specific,
      nucleic acid-binding proteins. The major difficulties to developing this method
      into a widely applicable protocol derived from the need for a massive enrichment
      and the inadvertent, extensive binding of nonspecific proteins to the bait. On
      the basis of a detailed analysis, we propose (i) a one-step fractionation of
      crude extracts on P11 phosphocellulose, followed by (ii) a discrete series of
      positive/negative selections on wild-type and site-mutated ligand DNA in a
      magnetic microparticulate format, with cobalt magnets, concatamerized and
      biotinylated ligands, selective salt conditions, and improved competitor DNAs. We
      also present rules for determining the precise number and order of selections.
      The approach and protocol allowed isolation of four, low-abundance transcription
      factors and repressors from 2 x 10(9) cultured leukemia cells. Captured proteins
      were 10-20,000-fold enriched from the nuclear extract, in a form and amounts that
      permitted facile MALDI-TOF and TOF/TOF MS-based protein identification. This is 1
      2 orders of magnitude better than many previous efforts and in a fraction of the
      time (approximately 1 factor/week). The method can be applied to any protein that
      binds DNA, including those with modest to low affinity, and bridges functional
      biochemical studies on replication, transcriptional regulation, and DNA repair
      with the analytical power of mass spectrometry-based proteomics.

PMID- 14640713
TI  - Attomole peptide analysis by high-pressure matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometry.
AB  - A new high-pressure matrix-assisted laser desorption/ionization (HP-MALDI) source
      for FTMS has recently been described (O'Connor et al. J. Am. Soc. Mass Spectrom.,
      in press). Improvements to the source design, including the incorporation of a
      new high-pressure gas channel plate, resulted in ions devoid of metastable
      fragmentation and also in increased sensitivity compared to the HP-MALDI
      prototype source design. The focus of this contribution is the evaluation of the
      current HP-MALDI FTMS configuration. The use of nonconductive sample surfaces,
      such as Parafilm and Teflon, was explored, and spectra from 30 amol of peptide
      applied to these surfaces were routinely obtained. In addition, the current limit
      of detection for this configuration is demonstrated to be 300 zmol for the
      phosphopeptide RRREEE(pS)EEEAA using multishot accumulation of the ions from 15
      laser shots in the hexapole and 1 scan. In addition, the performance of the new
      HP-MALDI FTMS configuration and its potential application for high-throughput
      proteomics analyses are discussed.

PMID- 14640714
TI  - Determination of enantiomeric compositions of amino acids by near-infrared
      spectrometry through complexation with carbohydrate.
AB  - A new method has been developed for the determination of enantiomeric
      compositions of a variety of compounds. The method is based on the use of the
      near-infrared technique to measure diastereomeric interactions between an added
      carbohydrate compound with both enantiomeric forms of an analyte followed by
      partial least-squares analysis of the data. The fact that the method works well
      with all three macrocyclic carbohydrates with different cavity size (i.e., alpha
      , beta-, and gamma-cyclodextrin) as well as with sucrose, which is a linear
      carbohydrate, clearly demonstrates that it is not necessary to have inclusion
      complex formation in order to produce effective diastereomeric interactions.
      Rather, a simple adsorption of the analyte onto a carbohydrate is sufficient.
      Since inclusion complex formation is not a requisite, this method is not limited
      to the amino acid studies here but is rather universal and sensitive as it can,
      in principle, be used to determine enantiomeric compositions for all types of
      compounds with only microgram concentration and enantiomeric excess as low as
      1.5%, in water or in a mixture of water and organic solvent. Furthermore, it does
      not rely on the use of rather expensive carbohydrates such as cyclodextrins but
      is equally as effective even with a simple and inexpensive carbohydrate such as
      sucrose.

PMID- 14640715
TI  - Speciation of dimethylarsinous acid and trimethylarsine oxide in urine from rats
      fed with dimethylarsinic acid and dimercaptopropane sulfonate.
AB  - Speciation of arsenic in urine from rats treated with dimethylarsinic acid
      (DMA(V)) alone or in combination with dimercaptopropane sulfonate (DMPS) were
      studied. Methods were developed for the determination of the methylarsenic
      metabolites, especially trace levels of dimethylarsinous acid (DMA(III)) and
      trimethylarsine oxide (TMAO), in the presence of a large excess of DMA(V).
      Success was achieved by using improved ion-exchange chromatographic separation
      combined with hydride generation atomic fluorescence detection. Micromolar
      concentrations of DMA(III) were detected in urine of rats fed with a diet
      supplemented with either 100 microg/g of DMA(V) or a mixture of 100 microg/g of
      DMA(V) and 5600 microg/g of DMPS. No significant difference in the DMA(III)
      concentration was observed between the two groups; however, there was a
      significant difference in TMAO concentrations. Urine from rats fed with the diet
      supplemented with DMA(V) alone contained 73 +/- 30 microM TMAO, whereas urine
      from rats fed with the diet supplemented with both DMA(V) and DMPS contained only
      2.8 +/- 1.4 microM TMAO. Solutions containing mixtures of 100 microg/L DMA(V) or
      TMAO and 5600 microg/L DMPS did not show reduction of DMA(V) and TMAO. The
      significant decrease (p < 0.001) of the TMAO concentration in rats administered
      with both DMA(V) and DMPS suggests that DMPS inhibits the biomethylation of
      arsenic.

PMID- 14640719
TI  - Magnetoelastic immunosensors: amplified mass immunosorbent assay for detection of
      Escherichia coli O157:H7.
AB  - A mass-sensitive magnetoelastic immunosensor for detection of Escherichia coli
      O157:H7 is described, based on immobilization of affinity-purified antibodies
      attached to the surface of a micrometer-scale magnetoelastic cantilever. Alkaline
      phosphatase is used as a labeled enzyme to the anti-E. coli O157:H7 antibody,
      amplifying the mass change associated with the antibody-antigen binding reaction
      by biocatalytic precipitation of 5-bromo-4-chloro-3-indolyl phosphate in a pH
      10.0 PBS solution. The detection limit of the biosensor is 10(2) E. coli O157:H7
      cells/mL. A linear change in the resonance frequency of the biosensor was found
      to E. coli O157:H7 concentrations ranging from 10(2) to 10(6) cells/mL.

PMID- 14640720
TI  - Enzyme-aided investigation of the substituent distribution in cationic potato
      amylopectin starch.
AB  - The distribution of substituents along the polymer chain in cationic potato
      amylopectin starch, modified in solution, granular slurry, or dry state, was
      investigated. The starch derivatives were successively hydrolyzed by different
      enzymes, followed by characterization of the hydrolysis products obtained by
      means of electrospray mass spectrometry (ESI-MS) and matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). ESI-MS and MALDI-MS were
      proved to be appropriate techniques for identification of the substituted
      hydrolysis products, for which there are no standard compounds available. No
      highly substituted oligomers were found in the hydrolysates, which was taken as
      an indication of a more or less homogeneous distribution of cationic groups in
      the amylopectin molecules. Furthermore, from the results obtained it was
      suggested that the enzymes cleave glucosidic linkages only between unsubstituted
      glucose units and, preferentially, linkages in sequences containing more than two
      adjacent unsubstituted units. The determination of the amount of unsubstituted
      glucose produced from every successive hydrolysis step revealed slight
      differences between the different starch samples with respect to the homogeneity
      of the substitution pattern. Among the three samples under investigation, starch
      cationized in solution was found to have the most and dry-cationized starch the
      least homogeneous distribution of substituents.

PMID- 14640721
TI  - Phosphorylation site identification via ion trap tandem mass spectrometry of
      whole protein and peptide ions: bovine alpha-crystallin A chain.
AB  - Tandem mass spectrometry was applied both to ions of a tryptic fragment and
      intact protein of bovine alpha-crystallin A chain to localize the single site of
      phosphorylation. The [M + 19H](19+) to [M + 11H](11+) charge states of both
      phosphorylated and unphosphorylated bovine alpha-crystallin A chain whole protein
      ions were subjected to collisional activation in a quadrupole ion trap. Ion
      parking was used to increase the number of parent ions over that yielded by
      electrospray. Ion-ion proton-transfer reactions were used to reduce the product
      ion charge states largely to +1 to simplify spectral interpretation. In agreement
      with previous studies on whole protein ion fragmentation, both protein forms
      showed backbone cleavages C-terminal to aspartic acid residues at lower charge
      states. The phosphorylated protein showed competitive fragmentation between
      backbone cleavage and the neutral loss of phosphoric acid. Analysis of which
      backbone cleavage products did or did not contain the phosphate was used to
      localize the site of phosphorylation to one of two possible serine residues. A
      tryptic digest of the bovine alpha-crystallin A chain yielded a phosphopeptide
      containing one missed cleavage site. The peptide provided information
      complementary to that obtained from the intact protein and localized the modified
      serine to residue 122. Fragmentation of the triply charged phosphopeptide yielded
      five possible serine phosphorylation sites. Fragmentation of the doubly charged
      phosphopeptide, formed by ion/ion proton-transfer reactions, positively
      identified the phosphorylation site as serine-122.

PMID- 14640722
TI  - A comparison of microLC/electrospray ionization-MS and GC/MS for the measurement
      of stable isotope enrichment from a [2H2]-glucose metabolic probe in T-cell
      genomic DNA.
AB  - Measurement of the proliferation of lymphocytes and other high-turnover cell
      populations in vivo can be accomplished through the incorporation of an
      isotopically labeled DNA precursor into actively dividing cells and the
      subsequent determination of the isotope enrichment in the isolated genomic DNA
      from selected cell populations. Two published gas chromatography/mass
      spectrometry (GC/MS) methods were successfully modified by our laboratory whereby
      a postinjection methylation reaction, rather than silylation or acetylation, was
      used to form a volatile derivative of deoxyadenosine (dA). We also developed a
      second robust microcapillary liquid chromatography-electrospray ionization
      (microLC-ESI)/MS method that is faster and more sensitive than the GC/MS method
      and does not require sample derivatization. Following administration of [6,6
      (2)H(2)]-glucose to human immunodeficiency virus-infected patients, peripheral
      blood was drawn; cells were obtained by lymphapheresis and fractionated. DNA was
      isolated from the desired cell subtypes and enzymatically hydrolyzed to the free
      deoxyribonucleosides. The digest was analyzed using both capillary GC/MS and
      microLC/ESI-MS to measure the levels of the dA and [(2)H(2)]-dA or their reaction
      products. Sample enrichments were calculated by comparison to standard curves
      prepared from dA and [(2)H(2)]-dA. The microLC/ESI-MS method required fewer
      cells, less sample preparation, shorter analysis times, and a single calibration
      curve. Overall, the microLC/ESI-MS method is superior to the GC/MS method in
      terms of precision and accuracy, while providing a 4-fold increase in sensitivity
      (from 20 pmol at 0.2% [(2)H(2)]-dA enrichment to 5 pmol at 0.1% [(2)H(2)]-dA
      enrichment).

PMID- 14640725
TI  - Isotope and affinity tags in photoreactive substance P analogues to identify the
      covalent linkage within the NK-1 receptor by MALDI-TOF analysis.
AB  - Photoreactive analogues of substance P (biotin sulfone-spacer (amino pentanoic or
      Gly(3))-Arg-Pro-Lys-Pro-(pBzl)Phe-Gln-Phe-Phe-Gly-Leu-Met(O(2))NH(2)) with or
      without isotope (deuterium) labeling have been synthesized. Deuteriums were
      present on (d)-biotin or epibiotin sulfone (D(3)), on the Gly(3) spacer linker
      (D(6)), or on the Gly in position 9 of SP (D(2)). Therefore, peptide analogues
      could be either unlabeled or tri-, penta-, or hexadeuterated. Results obtained
      with the use of these peptide analogues show that (d)-biotin sulfone and
      epibiotin sulfone are not recognized with the same affinity by streptavidin, with
      (d)-biotin sulfone displaying better affinity for the protein. Photolabeling of
      the human NK-1 receptor with a 1:1 molar ratio of nondeuterated and deuterated
      photoreactive substance P (SP) analogues in position 5, followed by combined
      digestions, purification, and MALDI-TOF mass spectrometry analysis, made the
      identification of the domain of the receptor covalently linked by the
      photoreactive SP analogue easier. Indeed, doublets in mass spectra were specific
      for the covalent complex whereas single peaks could be attributed to
      contaminating species. This method is particularly suitable when minute amounts
      of complex have to be analyzed, as in the case of highly hydrophobic G-protein
      coupled receptors.

PMID- 14640726
TI  - Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices.
AB  - This paper describes the compatibility of poly(dimethylsiloxane) (PDMS) with
      organic solvents; this compatibility is important in considering the potential of
      PDMS-based microfluidic devices in a number of applications, including that of
      microreactors for organic reactions. We considered three aspects of
      compatibility: the swelling of PDMS in a solvent, the partitioning of solutes
      between a solvent and PDMS, and the dissolution of PDMS oligomers in a solvent.
      Of these three parameters that determine the compatibility of PDMS with a
      solvent, the swelling of PDMS had the greatest influence. Experimental
      measurements of swelling were correlated with the solubility parameter, delta
      (cal(1/2) cm(-3/2)), which is based on the cohesive energy densities, c
      (cal/cm(3)), of the materials. Solvents that swelled PDMS the least included
      water, nitromethane, dimethyl sulfoxide, ethylene glycol, perfluorotributylamine,
      perfluorodecalin, acetonitrile, and propylene carbonate; solvents that swelled
      PDMS the most were diisopropylamine, triethylamine, pentane, and xylenes. Highly
      swelling solvents were useful for extracting contaminants from bulk PDMS and for
      changing the surface properties of PDMS. The feasibility of performing organic
      reactions in PDMS was demonstrated by performing a Diels-Alder reaction in a
      microchannel.

PMID- 14640737
TI  - Optical-trapping Raman microscopy detection of single unilamellar lipid vesicles.
AB  - Raman spectra of individual unilamellar phospholipid vesicles ( approximately 0.6
      microm in size) have been acquired by optical-trapping confocal Raman microscopy
      over the 900-3200-cm(-)(1) region. Raman scattering from the phospholipid bilayer
      of a single, trapped liposome could be detected, along with molecular species
      trapped within the vesicle. The Raman spectra of vesicles prepared from four
      different phosphatidylcholine lipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dilauroyl-sn
      glycero-3-phosphocholine (DLPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine
      (DOPC), could be readily distinguished by evaluating differences in the skeletal
      C-C and C-H stretching modes of the acyl hydrocarbon tails. These differences
      correlate with changes in lipid organization for different gel to liquid-crystal
      transition temperatures (T(m)): 41, 24, 7, and -20 degrees C for DPPC, DMPC,
      DLPC, and DOPC, respectively. The spectra could be acquired on the same trapped
      vesicle for several hours, which allowed the permeability of the bilayer to be
      investigated by monitoring the leakage of perchlorate anions from the vesicle.
      Vesicles prepared from pure DPPC or DOPC, with gel to liquid-crystal transition
      temperatures well above and well below room temperature, exhibited no detectable
      anion transfer. DLPC and DMPC vesicles permitted rapid ion transfer across the
      bilayer. The lengths of hydrocarbon tails were shorter in these two lipids, which
      could indicate that shorter chains lower the hydrophobic barrier of a membrane to
      ion transport. While the DMPC chains were longer than DLPC with a correspondingly
      higher T(m), the temperature of the experiment corresponds to the T(m) of DMPC,
      and domain boundaries between gel and liquid-crystal phases could contribute to
      high membrane permeability.

PMID- 14640732
TI  - Detection of attomole quantities [correction of quantitites] of DNA targets on
      gold microelectrodes by electrocatalytic nucleobase oxidation.
AB  - The electrochemical detection of nucleic acid targets at low concentrations has a
      number of applications in diagnostics and pharmaceutical research. Self-assembled
      monolayers of alkanethiol-derivatized oligonucleotides on gold electrodes provide
      a useful platform for such detectors, and the electrocatalytic oxidation of
      nucleobases included in the DNA targets is a particularly sensitive method of
      electrochemical detection. A strategy has been developed for combining these two
      aspects by substituting either 7,8-dihydro-8-oxoguanine (8G) or 5-aminouridine
      (5U) into DNA targets. Upon hybridization of targets containing these modified
      nucleobases, electrocatalytic signals at probe-modified gold electrodes are
      observed in the presence of Os(bpy)(3)(2+), which oxidizes both 8G and 5U upon
      oxidation to the Os(III) state. Self-assembled monolayers were prepared on both
      macro (1.6 mm) and micro (25 microm) gold electrodes using published procedures
      involving C6-terminated alkanethiol oligonucleotides and mercaptohexanol as the
      diluent. The extent of electrode modification by the modified probe was assessed
      using radiolabeling and a standard chronocoulometry method; both approaches gave
      loading levels within expected ranges ((1-6) x 10(12) molecules/cm(2)).
      Hybridization of the modified targets where the non-native nucleobase was
      incorporated by solid-phase synthesis produced electrocatalytic signals from
      strands that were independently detected using radiolabeling and
      chronocoulometry. This result was used as a basis to develop an on-electrode
      amplification scheme where Taq polymerase was used to extend the immobilized DNA
      probes from solution-phase polymeric templates using modified
      nucleotriphosphates. This reaction produced an electrode that was modified with
      extended DNA containing the appropriate modified nucleotide. Radiolabeled
      nucleotide triphosphates were used to confirm the desired on-electrode DNA
      synthesis. When these electrodes were cycled in the presence of Os(bpy)(3)(2+),
      electrocatalytic signals were observed when as little as 40 amol (400 fM) of the
      desired target was present in the hybridization solution.

PMID- 14640738
TI  - DNA hybridization using surface plasmon-coupled emission.
AB  - We describe a new approach to measuring DNA hybridization using surface plasmon
      coupled emission (SPCE). Excited fluorophores are known to couple with surface
      oscillations of electrons in thin metal films, typically 50 nm thick silver on a
      glass prism. These surface plasmons then radiate into the glass at a sharply
      defined angle determined by the emission wavelength and the optical properties of
      the glass and metal. This radiation has the same spectral profile as the emission
      spectrum of the fluorophores. We studied the emission due to Cy3-labeled DNA
      oligomers bound to complementary unlabeled oligomers which were themselves bound
      to the metal surface. Hybridization resulted in SPCE due to Cy3-DNA into the
      prism. Directional SPCE was observed whether the sample was illuminated from the
      sample side or through the glass substrate at the surface plasmon angle for the
      excitation wavelength. A large fraction of the total potential emission is
      coupled to the surface plasmons resulting in improved sensitivity. When
      illuminated through the prism at the surface plasmon angle, the sensitivity is
      increased due to the enhanced intensity of the resonance evanescent field. It is
      known that SPCE depends on proximity to the silver surface. As a result, changes
      in emission intensity are observed due to fluorophore localization even if
      hybridization does not affect the quantum yield of the fluorophore. The use of
      SPCE resulted in suppression of interfering emission from a noncomplementary Cy5
      DNA oligomers due to weaker coupling of the more distant fluorophores with the
      surface plasmons. We expect SPCE to have numerous applications to nucleic acid
      analysis and for the measurement of bioaffinity reactions.

PMID- 14640739
TI  - Two-beam fluorescence cross-correlation spectroscopy for simultaneous analysis of
      positive and negative ions in continuous-flow capillary electrophoresis.
AB  - Two-beam fluorescence cross-correlation spectroscopy was used for multicomponent
      electrophoretic analysis of positive and negative ions flowing continuously, and
      in opposite directions, through a polymer-coated electrophoresis capillary. Cross
      correlation analysis of the fluorescence monitored from two spatially offset
      microscopic detection volumes revealed the magnitude and direction of the
      electrophoretic flow velocity of each analyte. This enabled resolution of a three
      component mixture containing nanomolar concentrations of cationic rhodamine 6G
      and anionic 5-carboxytetramethylrhodamine (TAMRA) and TAMRA-labeled single
      stranded DNA in aqueous buffer. The relative concentrations of each analyte,
      determined from the cross-correlation analysis, agreed with known values within
      experimental error. This technique is sensitive to molecular processes occurring
      on a millisecond time scale and will prove useful for monitoring rapid
      fluctuations in the magnitude and direction of the electrophoretic flow velocity
      caused by spontaneous chemical reactions or conformational transformations at
      thermodynamic equilibrium.

PMID- 14640740
TI  - Mass spectrometry of intracellular and membrane proteins using cleavable
      detergents.
AB  - Detergents have been used to enhance the solubility of hydrophobic biomolecules
      for decades. Despite the widespread use of detergents in biochemistry, the
      presence of these molecules often complicates further analysis by mass
      spectrometry. This study presents a solution to this problem by outlining a
      method utilizing a novel cleavable detergent, 3-[3-(1,1-bisalkyloxyethyl)pyridin
      1-yl]propane-1-sulfonate (PPS). This detergent can be used to extract protein
      contained within the interior of the cell by disrupting cell membranes. Once the
      proteins are free from the cell, PPS also assists in protein solubilization by
      shielding the hydrophobic regions of the newly extracted protein from unfavorable
      interactions with water. The added advantage of PPS over conventional detergents
      such as sodium dodecyl sulfate or n-octylglucoside is that the detergent
      properties that interfere with MALDI mass spectrometry can be eliminated prior to
      analysis. PPS was found to improve sensitivity in MALDI analyses of both soluble
      proteins and membrane proteins without degrading spectral quality. The virtues of
      this strategy were applied to whole cell extracts. Analysis of these extracts
      resulted in an overall increase in both the number of peaks observed and overall
      signal intensity.

PMID- 14640741
TI  - Automated statistical analysis of protein abundance ratios from data generated by
      stable-isotope dilution and tandem mass spectrometry.
AB  - We describe an algorithm for the automated statistical analysis of protein
      abundance ratios (ASAPRatio) of proteins contained in two samples. Proteins are
      labeled with distinct stable-isotope tags and fragmented, and the tagged peptide
      fragments are separated by liquid chromatography (LC) and analyzed by
      electrospray ionization (ESI) tandem mass spectrometry (MS/MS). The algorithm
      utilizes the signals recorded for the different isotopic forms of peptides of
      identical sequence and numerical and statistical methods, such as Savitzky-Golay
      smoothing filters, statistics for weighted samples, and Dixon's test for
      outliers, to evaluate protein abundance ratios and their associated errors. The
      algorithm also provides a statistical assessment to distinguish proteins of
      significant abundance changes from a population of proteins of unchanged
      abundance. To evaluate its performance, two sets of LC-ESI-MS/MS data were
      analyzed by the ASAPRatio algorithm without human intervention, and the data were
      related to the expected and manually validated values. The utility of the
      ASAPRatio program was clearly demonstrated by its speed and the accuracy of the
      generated protein abundance ratios and by its capability to identify specific
      core components of the RNA polymerase II transcription complex within a high
      background of copurifying proteins.

PMID- 14640742
TI  - Global protein identification and quantification technology using two-dimensional
      liquid chromatography nanospray mass spectrometry.
AB  - A simple and reliable method is described here for the identification and
      relative quantification of proteins in complex mixtures using two-dimensional
      liquid chromatography/tandem mass spectrometry. The method is based on the
      classical proteomic analysis where proteins are digested with trypsin and the
      resulting peptides are separated by multidimensional liquid chromatography. The
      separated peptides are analyzed by tandem mass spectrometry and identified via a
      database search algorithm such as SEQUEST. The peak areas (integrated ion counts
      over the peptide elution time) of all identified peptides are calculated, and the
      relative concentration of each protein is determined by comparing the peak areas
      of all peptides from that protein in one sample versus those from the other.
      Using this strategy, we compared the relative level of protein expression of A431
      cells (an epidermal cell line) grown in the presence or absence of epidermal
      growth factor (EGF). Our results are consistent with the published observations
      of the transient effects of EGF. In addition, the difference in the
      concentrations of several phosphopeptides determined in our studies suggests the
      possibility of several new targets involved in the EGF cell-signaling pathway.
      This global protein identification and quantification technology should prove to
      be a valuable means for comparing proteomes in biological samples subjected to
      differential treatments.

PMID- 14640743
TI  - Improving fluorescent DNAzyme biosensors by combining inter- and intramolecular
      quenchers.
AB  - A previously reported DNAzyme-based biosensor for Pb(2+) has shown high
      sensitivity and selectivity at 4 degrees C. In the system, the substrate and the
      enzyme strand of the DNAzyme are labeled with a fluorophore and a quencher,
      respectively. In the presence of Pb(2+), the substrate strand is cleaved by the
      enzyme strand, and the release of the cleaved fragment results in significant
      fluorescence increase. However, the performance of the sensor decreases
      considerably if the temperature is raised to room temperature because of high
      background fluorescence. A careful analysis of the sensor system, including
      measurement of the melting curve and fluorescence resonance energy-transfer
      (FRET) study of the free substrate, suggests that a fraction of the fluorophore
      labeled substrate strand is dissociated from the enzyme strand, resulting in
      elevated background fluorescence signals at room temperature. To overcome this
      problem, we designed a new sensor system by introducing both inter- and
      intramolecular quenchers. The design was aided by the FRET study that showed the
      dissociated substrate maintained a random coil conformation with an end-to-end
      distance of approximately 39 A, which is much shorter than that of the fully
      extended DNA. With this new design, the background fluorescence was significantly
      suppressed, with 660% increase of fluorescence intensity as compared to 60%
      increase for the previous design. This suppression of background fluorescence
      signals was achieved without losing selectivity of the sensor. The new design
      makes it possible to use the sensor for practical applications in a wide
      temperature range. The design principle presented here should be applicable to
      other nucleic acid-based biosensors to decrease background fluorescence.

PMID- 14640744
TI  - Antemortem identification of bovine spongiform encephalopathy from serum using
      infrared spectroscopy.
AB  - Since 1986, more than 180 000 clinical cases of bovine spongiform encephalopathy
      (BSE) have been observed in the U.K. alone. Most of these cases were confirmed by
      postmortem examination of brain tissue. However, BSE-related risk assessment and
      risk management would greatly benefit from antemortem testing on living animals.
      A serum-based test could allow for screening of the cattle population; thus, even
      a BSE eradication program would be conceivable. Here we report on a novel method
      for antemortem BSE testing, which combines infrared spectroscopy of serum samples
      with multivariate pattern recognition analysis. A classification algorithm was
      trained using infrared spectra of bovine sera from more than 800 animals
      (including BSE-positive, healthy controls and animals suffering from classical
      viral or bacterial infections). In two validation studies, sensitivities of 85
      and 84% and specificities of 86 and 91% were achieved, respectively. The
      combination of classification algorithms increased the sensitivity and
      specificity of BSE detection to 96 and 92%, respectively.

PMID- 14640745
TI  - Explanatory optimization of protein mass spectrometry via genetic search.
AB  - Optimizing experimental conditions for the effective analysis of intact proteins
      by mass spectrometry is challenging, as many analytical factors influence the
      spectral quality, often in very different ways for different proteins and
      especially with complex protein mixtures. We show that genetic search methods are
      highly effective in this kind of optimization and that it was possible in 6
      generations with a total of <500 experiments out of some 10(14) to find good
      combinations of experimental variables (electrospray ionization mass spectral
      settings) that would not have been detected by optimizing each variable alone
      (i.e., the search space is epistatic). Moreover, by inspecting the evolution of
      the variables to be optimized using genetic programming, we discovered an
      important relationship between two of the mass spectrometer settings that
      accounts for much of this success. Specifically, the conditions that were evolved
      included very low values of skimmer 1 voltage (the sample cone) and a skimmer 2
      voltage (extraction cone) above a threshold that would nevertheless minimize the
      potential difference between the sample and extraction skimmers. The discovery of
      this relationship demonstrates the hypothesis-generating ability of genetic
      search in optimization processes where the size of the search space means that
      little or no a priori knowledge of the optimal conditions is available.

PMID- 14640746
TI  - Splitter imperfections in annular split-flow thin separation channels:
      experimental study of nonspecific crossover.
AB  - The separation performance of a split-flow thin (SPLITT) separation device
      depends on uniformity of channel thickness and the precise placement of the flow
      splitters at fixed distances between the channel walls. The observation of
      nonspecific crossover, that is, the transport of sample materials across the
      channel thickness without the influence of an applied field, has routinely been
      taken to indicate the presence of irregularities in splitter shape or placement.
      Computational fluid dynamics software may be used to predict the influence of
      splitter imperfections on nonspecific crossover, where it is assumed that sample
      transport is by convection alone. A previous study has shown how small inlet
      splitter imperfections can account for the relatively low levels of nonspecific
      crossover observed with typical annular SPLITT devices. This study, however,
      could not distinguish between the possible sources of nonspecific crossover;
      hydrodynamic lift or shear-induced diffusion could have contributed. To confirm
      the validity of the computational approach, a series of experiments has been
      carried out on a channel having a deliberately and severely bent splitter.
      Nonspecific crossover was measured for a range of inlet and outlet flow rate
      ratios, with the bent splitter placed at both the channel inlet and outlet. The
      severity of the splitter distortion was sufficient to produce significant
      nonspecific crossover over a wide range of flow conditions. Good agreement was
      found between experiment and prediction based on computational fluid dynamics,
      with experiment generally showing only slightly higher crossover than prediction.
      The quantitative agreement for this extreme case suggests that the contribution
      to nonspecific crossover due to geometrical imperfections can be well described
      using computational fluid dynamics.

PMID- 14640749
TI  - Multilabeling biomolecules at a single site. 1. Synthesis and characterization of
      a dendritic label for electrochemiluminescence assays.
AB  - Ultrasensitive bioanalytical assays are of great value for early detection of
      human diseases and pathogens. The sensitivities of immunoassays and DNA probing
      can be enhanced by multilabeling the biorecognition partner used for affinity
      based assays. However, the bioreactivity of biomolecules is affected by a high
      degree of multilabeling at multiple functional sites. It is proposed that
      dendritic scaffoldings be used to link multiple signal-generating units to a
      single site with potentially minimum impact on the bioaffinity. A prototype
      label, a zeroth-generation dendron, bearing three [Ru(bpy)(3)](2+) units for
      electrochemiluminescence (ECL) assays was synthesized and characterized
      preliminarily by spectroscopic, electrochemical, and ECL methods. No evidence of
      interaction between the neighboring [Ru(bpy)(3)](2+) units in the label molecule
      was found from these characterizations. Both the photoluminescence and ECL of the
      prototype label have features very similar to those of mononuclear
      [Ru(bpy)(3)](2+) compounds. Labeling a model protein with a triad of
      [Ru(bpy)(3)](2+) at one NH(2) position was demonstrated. The results reported
      here provide support to applying the proposed multilabeling strategy to affinity
      based bioanalytical assays.

PMID- 14640752
TI  - An assay of ganglioside using fluorescence image analysis on a thin-layer
      chromatography plate.
AB  - A new and simple fluorometric method for determine quantities of gangliosides
      ranging from pico- to nanomoles is reported. Spraying hydrochloric acid followed
      by a heating treatment, sugars (glucose, galactose, fucose, N
      acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid (sialic acid)),
      gangliosides (G(M1), G(D1a), G(T1b)), and asialoganglioside (asialoG(M1)) on thin
      layer chromatography plates produced fluorescence under 365-nm UV light. This
      fluorescence production of each sample was greatly dependent on the heating
      temperature. As sialic acid fluoresced readily at lower temperature
      (approximately 90 degrees C), we were able to distinguish sialic acid easily from
      other sugars tested. To determine gangliosides based on this sialic acid
      fluorescence, calibration curves for gangliosides were obtained by high
      performance thin-layer chromatography and the image-analyzing system equipped
      with a CCD camera. The observed fluorescence images were analyzed using image
      analyzing software packages and the determined calibration curves for ganglioside
      bound sialic acids were reproducible and showed a high linearity in a wide range
      from 47 pmol to 4.5 nmol. Since the fluorescence from sialic acid is easily
      measurable on TLC plates and is sensitive over a wide range of sample
      concentration, the present method is applicable for quantitative determination of
      gangliosides.

PMID- 14640754
TI  - Monolithic silica-based capillary reversed-phase liquid
      chromatography/electrospray mass spectrometry for plant metabolomics.
AB  - Application of C18 monolithic silica capillary columns in HPLC coupled to ion
      trap mass spectrometry detection was studied for probing the metabolome of the
      model plant Arabidopsis thaliana. It could be shown that the use of a long
      capillary column is an easy and effective approach to reduce ionization
      suppression by enhanced chromatographic resolution. Several hundred peaks could
      be detected using a 90-cm capillary column for LC separation and a noise
      reduction and automatic peak alignment software, which outperformed manual
      inspection or commercially available mass spectral deconvolution software.

PMID- 14640755
TI  - Analysis of self-assembled monolayer interfaces by electrospray mass
      spectrometry: a gentle approach.
AB  - A general mass spectrometry technique for the characterization of alkanethiol
      modified surfaces is presented. Alkanethiol self-assembled onto a gold surface
      (in this case, peptides were attached to the gold surface via a thiolate bond)
      was reductively desorbed in 0.05 M KOH in the presence of octadecyl-derivatized
      silica gel. The peptide adsorbed onto the silica gel, whereupon it could be
      filtered, washed to remove any salts, and then eluted using a mixture of 4:1 v/v
      methanol/water. The eluant containing the peptide was injected into a Fourier
      transform ion-cyclotron resonance mass spectrometer (FTICR/MS) via electrospray
      ionization. The spectrum showed no fragmentation of the peptide, demonstrating
      the gentleness of the technique. This simple procedure is not limited to FTICR/MS
      and could be adapted to other mass spectrometers.

PMID- 14640757
TI  - Direct electrochemical detection of oligonucleotide hybridization on poly(5
      hydroxy-1,4-naphthoquinone- co-5-hydroxy-3-thioacetic acid-1,4-naphthoquinone)
      film.
AB  - We describe the construction of a new DNA-modified electrode based on an
      electroactive film. 5-Hydroxy-1,4-naphthoquinone is coelectrooxidized with 5
      hydroxy-3-thioacetic acid-1,4-naphthoquinone to give a copolymer, presenting both
      electroactive and chemically reactive groups. The carboxylic function acts as a
      precursor for the covalent grafting of ODN probes while the quinone group acts as
      the transduction element of hybridization. Electrochemical detection was
      performed by differential pulse voltammetry in the electroactivity domain of the
      quinone group (i.e., at very low potentials, 0 to -0.8 V vs SCE). A very clear
      modification of the redox activity is observed between unmodified and probe
      modified films and especially upon addition of target ODN.

PMID- 14640758
TI  - Silver-induced enhancement of thiochrome-based peroxide measurements.
AB  - Thiamine is presently one of the most attractive substrates used for sensitive
      fluorometric measurements of peroxides. Thiochrome (TC), a highly fluorescent
      product, is formed in enzyme-mediated oxidations. It is assumed that H(2)O(2) is
      nearly quantitatively converted to TC. The reaction cannot differentiate H(2)O(2)
      from many other peroxides such as methylhydroperoxide (MHP); to perform
      differential measurements, H(2)O(2) can first be selectively destroyed by a
      suitable catalyst such as MnO(2). In substituting Ag(2)O for MnO(2) to accomplish
      the selective destruction of H(2)O(2), we achieved the stated objective but were
      puzzled by a 3-fold increase in the MHP response in the presence of Ag(2)O. It
      was soon discovered that traces of dissolved Ag(+) and Hg(2+) can dramatically
      increase the yield of TC in this reaction from either H(2)O(2) or MHP; the normal
      yield in fact is only 20%. We present here a reaction scheme and kinetic model
      that adequately describes this behavior and should provide a path to
      substantially increase the sensitivity of this important assay method.

PMID- 14640761
TI  - Optical systems for in vivo molecular imaging of cancer.
AB  - Progress toward a molecular characterization of cancer would have important
      clinical benefits; thus, there is an important need to image the molecular
      features of cancer in vivo. In this paper, we describe a comprehensive strategy
      to develop inexpensive, rugged and portable optical imaging systems for molecular
      imaging of cancer, which couples the development of optically active contrast
      agents with advances in functional genomics of cancer. We describe initial
      results obtained using optically active contrast agents to image the expression
      of three well known molecular signatures of neoplasia: including over expression
      of the epidermal growth factor receptor (EGFR), matrix metallo-proteases (MMPs),
      and oncoproteins associated with human papillomavirus (HPV) infection. At the
      same time, we are developing inexpensive, portable optical systems to image the
      morphologic and molecular signatures of neoplasia noninvasively in real time.
      These real-time, portable, inexpensive systems can provide tools to characterize
      the molecular features of cancer in vivo.

PMID- 14640762
TI  - Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia.
AB  - Reflectance and fluorescence spectroscopies have shown great promise for early
      detection of epithelial dysplasia. We have developed a clinical reflectance
      spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial
      dysplasia. This clinical instrument, the FastEEM, collects white light
      reflectance and fluorescence excitation-emission matrices (EEM's) within a
      fraction of a second. In this paper we describe the FastEEM instrumentation,
      designed for collection of multi-modal spectroscopic data. We illustrate its
      performance using tissue phantoms with well defined optical properties and
      biochemicals of known fluorescence properties. In addition, we discuss our plans
      to develop a system that combines a multi-spectral imaging device for wide area
      surveillance with this contact probe device.

PMID- 14640763
TI  - Development of a fluorescence detection system using optical parametric
      oscillator (OPO) laser excitation for in vivo diagnosis.
AB  - In this work, the development and applications of a fluorescence detection system
      using optical parametric oscillator (OPO) laser excitation for in vivo disease
      diagnosis including oral carcinoma are described. The optical diagnosis system
      was based on an OPO laser for multi-wavelength excitation and time-resolved
      detection. The pulsed Nd-YAG-pumped OPO laser system (6 ns, 20 Hz) is compact and
      has a rapid, broad, and uniform tuning range. Time-gated detection of intensified
      charge-coupled device (ICCD) making use of external triggering was used to
      effectively eliminate the laser scattering and contribute to the highly sensitive
      in vivo measurements. Artificial tissue-simulating phantoms consisting of
      polystyrene microspheres and tissue fluorophores were tested to optimize the
      gating parameters. 51-ns gate width and 39-ns gate delays were determined to be
      the optimal parameters for sensitive detection. In vivo measurements with the
      optical diagnosis system were applied to esophagus, stomach, and small intestine
      using an endoscope in canine animal studies. The rapid tuning capability of the
      optical diagnosis system contributed greatly to the optimization of wavelength
      for the observation of porphyrin in the small intestine. When the small intestine
      was thoroughly washed with water, the emission band which corresponds to
      porphyrin disappeared. Based on this observation, it was concluded that the
      detected signal was yielded by porphyrin-containing bile secretion. Also,
      multispectral analyses using multiple excitations from 415 to 480 nm at 5 nm
      intervals confirmed the porphyrin detection in the small intestine. The optical
      diagnosis system was also applied to the detection of human xenograft of oral
      carcinoma in mice using 5-aminolevulinic acid (5-ALA) which is a photodynamic
      therapy (PDT) drug. Significant differences in protoporphyrin IX fluorescence
      intensity between normal and tumor tissue could be obtained 2 hours after the
      injection of 5-ALA into mice due to the preferential accumulation of 5-ALA in
      tumors. Results reported herein demonstrate potential capabilities of the LIF-OPO
      system for in vivo disease diagnosis.

PMID- 14640765
TI  - Tissue characterization by quantitative optical imaging methods.
AB  - Optical methods have a long history in the field of medical diagnosis. The
      biomolecular specificity possible with optical methods has been particularly
      valuable in microscopy and histopathology while in vivo imaging of deep
      structures has traditionally been the domain of X-ray and MRI. The use of optical
      methods in deep tissue has been limited by multiple-scattering which blurs or
      distorts the optical signal. New stochastic methods which account for multiple
      scattering have been developed that are extending the usefulness of optical
      methods deep into tissue. In optical mammography, photons may travel through 10
      cm of tissue before arriving at the detector. We have developed a method for
      quantifying parameters of anomalous sites in breast tissue that may be used for
      functional characterization of tumors. In other work presented here, we are
      developing fluorescence based methods to detect and monitor tumor status. The
      immune response to a tumor is a target for fluorescently labeled specific
      antibodies. We have developed a method to localize the tumor site using CW
      fluorescence. Additionally, we have developed a method which uses time-resolved
      data and capitalizes on probe lifetime sensitivity to metabolic parameters such
      as pH and temperature to obtain functional information from the tumor site.

PMID- 14640764
TI  - Investigating sun-damaged skin and actinic keratosis with optical coherence
      tomography: a pilot study.
AB  - Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical
      manifestation in the multistep process of skin carcinogenesis to invasive
      squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts.
      Noninvasive measures of AK severity are needed to assess the efficacy of
      chemoprevention agents. We performed a pilot study on 20 participants to
      investigate the OCT appearance of sun-protected skin of the upper inner arm as
      well as sun-damaged skin and early AKs of the dorsal forearms, and to determine
      if features or quantitative measures in Optical Coherence Tomography (OCT) images
      could be used to reliably differentiate between these categories. OCT images of
      upper inner arm (normal appearing skin) showed skin layers and features (stratum
      corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally
      in this participant group the subcutaneous fat layer was usually identified. Sun
      damaged skin was characterized by increased signal in the epidermis and rapid
      attenuation of light. AKs were diverse in appearance but frequently characterized
      by high surface reflection, the presence of a low-signal band in the stratum
      corneum, and heterogeneous appearance in the epidermis/dermis. Significant
      differences were found between skin categories using measures of stratum corneum
      and epidermal/dermal depths and intensities. The presence of a dark band in the
      stratum corneum was 79% sensitive and 100% specific for AK. This study indicates
      that OCT holds promise as a useful technique for identifying and characterizing
      AKs and monitoring their response to chemoprevention agents.

PMID- 14640766
TI  - An operational near-infrared fluorescence imaging system prototype for large
      animal surgery.
AB  - Near-infrared (NIR) fluorescence imaging has the potential to revolutionize human
      cancer surgery by providing sensitive, specific, and real-time intraoperative
      visualization of normal and disease processes. We have previously introduced the
      concept of a low-cost, safe, and easy-to-use NIR fluorescence imaging system that
      permits the surgeon to "see" surgical anatomy and NIR fluorescence
      simultaneously, non-invasively, with high spatial resolution, in real-time, and
      without moving parts. In this study, we present an operational prototype designed
      specifically for use during large animal surgery. Such a system serves as a
      foundation for future clinical studies. We discuss technical considerations, and
      provide details of the implementation of subsystems related to excitation light,
      light collection, computer, and software. Using the prototype, and the clinically
      available NIR fluorophore indocyanine green, we demonstrate vascular imaging in
      35 kg pigs. Cancer-specific applications of this imaging system include image
      guided cancer resection with real-time assessment of surgical margins, image
      guided sentinel lymph node mapping, intraoperative mapping of tumor and normal
      vasculature, image-guided avoidance of critical structures such as nerves, and
      intraoperative detection of occult metastases in the surgical field. Taken
      together, this study describes an optical imaging system engineered for eventual
      translation to the clinic.

PMID- 14640767
TI  - Comparison of water and lipid content measurements using diffuse optical
      spectroscopy and MRI in emulsion phantoms.
AB  - We present a quantitative comparison of lipid and water signals obtained from
      broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging
      (MRI). DOS and MRI measurements were performed on an identical set of emulsion
      phantoms that were composed of different water/soybean oil fractions. Absolute
      concentrations of water and lipid ranging from 35-94% and 63-6%, respectively
      were calculated from quantitative broadband near-infrared (NIR) absorption
      spectra (650-1000 nm). MR images of fat and water were separated using the three
      point Dixon technique. DOS and MRI measured water and lipid were highly
      correlated (R(2) = 0.98 and R(2) = 0.99, respectively) suggesting that these
      techniques are complementary over a broad range of physiologically relevant water
      and lipid values. In addition, comparison of DOS derived concentrations to the
      MRI "gold standard" technique validates our quantitation approach and permits
      estimation of DOS accuracy and sensitivity in vivo.

PMID- 14640768
TI  - Dynamic infrared imaging of newly diagnosed malignant lymphoma compared with
      Gallium-67 and Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography.
AB  - Staging and therapy monitoring of malignant lymphomas relies heavily on imaging
      using arbitrary size criteria from computed tomography (CT) and sometimes non
      specific radionuclide studies to assess the activity of the disease. Treatment
      decisions are based on early assessment of the response to therapy and the
      residual volume of the disease. Our initial experience is reported using a new
      noninvasive, inexpensive, and reproducible passive imaging modality, Dynamic
      Infrared Imaging (DIRI), which may add a new dimension to functional imaging.
      This system relies on its ability to filter the raw infrared signal using
      biological oscillatory behavior. It detects and analyzes minute oscillations of
      temperature and heat distribution in tumors.

PMID- 14640769
TI  - Effect of alanine energy response and phantom material on depth dose measurements
      in ocular proton beams.
AB  - The usefulness of the alanine dosimeter for proton beams has been demonstrated
      before. In this paper a literature overview is given of the application of
      alanine in proton beam dosimetry. The energy dependence of the dosimeter has been
      investigated and Monte Carlo calculations were performed to investigate the
      influence of this energy dependence on a Bragg curve as well as to explain some
      phenomena related to the use of alanine in a solid phantom that were reported in
      the literature.

PMID- 14640770
TI  - Quantitative analysis of three-dimensional conformal radiotherapy techniques for
      posterior fossa treatment in children.
AB  - Numerous beam directions using 3-D conformal techniques can be employed in
      treating tumors in the posterior fossa, each with characteristic normal tissue
      exposure along the entrance and exit trajectory. A representative variety of beam
      configurations were modeled in a modern computer planning system initially with
      the entire posterior fossa as the target. These beams were quantitatively scored
      using criteria based on integral doses for both low dose and high dose effects
      encompassing a variety of critical normal structures, thus identifying strengths
      and weaknesses of each beam. By blocking portions of a particular beam accounting
      for unfavorable scores, a map of "zones" within the posterior fossa ideally
      treated by a certain beam or beams could be constructed. No universally ideal
      photon beam arrangement for the entire posterior fossa target could be
      identified. However, using single beam analysis, the strengths and weaknesses of
      particular strategies could be quantified. For example, vertex beams treating the
      cerebellar hemispheres allow the greatest sparing of cochlea and hypothalamus but
      at the cost of increased low to moderate dose to the supratentorial brain. Using
      the constructed maps identifying "zones" appropriately treated by a given beam or
      beams, three-dimensional conformal treatment plans with favorable dose-volume
      statistics can be designed based on previously defined normal tissue tolerance
      considerations. It is shown how this approach can be individualized based on
      specific patient characteristics (e.g., age). We conclude that radiotherapy
      directed to the posterior fossa can be optimized based on systematic assessment
      of individual beam contributions to normal tissues. This technique allows fast
      selection of treatment beams based on known normal tissue anatomical and
      tolerance information. Further studies will be required regarding long term
      effects of various radiation doses on specific volumes of normal tissue in order
      to individualize beam selection. When treating children, knowledgeable
      consideration of these beam characteristics can help avoid late effects.

PMID- 14640771
TI  - Issues related to monitoring the safety of over-the-counter (OTC) medicines.
AB  - Pharmaceutical advances over the past 50 years have benefited many people in
      terms of disease prevention and management. However, probably without exception,
      most pharmaceutical products can cause adverse consequences of varying severity
      and frequency. In the last 10 years, many medicines that were originally
      prescription only have now become available over the counter (OTC), either from
      pharmacies or other general retail outlets. The volume and value of OTC medicine
      sales have increased accordingly. These switches have been well regulated and
      based on clear criteria and evidence of safety. Benefits of the changes include
      increased convenience to patients, greater self-management of minor ailments and
      a reduction in government drug expenditure.However, there are important
      differences between medicines supplied OTC and on medical prescription. With OTC
      medicines there is generally less healthcare professional input into the
      recommendation or ongoing monitoring of use. There is an absence of records per
      se, or linkage to other medication records elsewhere, and most countries allow
      direct-to-consumer advertising of the product. Taken together these differences
      can result in inappropriate expectations, demand and use of the OTC medicines,
      with limited opportunity for ongoing patient follow-up and monitoring of safety.
      Methodologies for pharmacy-based epidemiological studies of OTC medicines need to
      be developed. Studies should be large enough to detect associations that might
      exist, and to consider other explanations for associations such as chance, bias
      or confounding. There have already been some pilot studies with encouraging
      results with respect to follow-up rates. Outcome data however have usually been
      self-reported and the studies have lacked a suitable comparison group. Purchasers
      and suppliers of OTC medicines should also be made aware of, and encouraged to
      use, existing systems for spontaneous reporting of suspected adverse events, such
      as the Yellow Card Scheme in the UK. While available OTC medicines are perceived
      to be generally safe, problems have occasionally arisen with some earlier
      switched products (e.g. terfenadine). There have also been concerns about some
      traditional herbal and homeopathic remedies such as St John's wort. While such
      adverse events are rare, they emphasise the need for healthcare professionals and
      the public to understand and manage such risks. Many doctors are unaware of the
      range of OTC preparations available, and therefore do not consider them as a
      possible cause of presenting symptoms. Neither do they take them into account
      when making a new prescribing decision. The public need to be aware that OTC
      medicines should be treated with the same care as prescribed medicines, and that
      advice on recommended dose, contraindications and interactions should be adhered
      to.

PMID- 14640772
TI  - Drug interactions between herbal and prescription medicines.
AB  - Until reports of interactions between St John's wort and drugs such as digoxin,
      warfarin, protease inhibitors and oral contraceptives began to appear, very few
      herb-drug interactions were documented. These are now becoming more common,
      although still rare compared with drug-drug interactions. In the absence of hard
      data, potential interactions are being highlighted, and this review attempts to
      distinguish between the speculative and the proven. The subject is approached
      from a therapeutic point of view since in most cases the patient is already
      taking one or more prescription drugs, and the question is whether or not it is
      safe for a particular herb to be added to the regimen. Although many of the
      examples of herb-drug interactions are minor or theoretical at present, the fact
      remains that some are serious and life threatening, and these almost exclusively
      concern cyclosporin, anticoagulants, digoxin, antidepressants and protease
      inhibitors, taken with the herb St John's wort. Ginkgo and ginseng are implicated
      in a number of reports, but many of these are unsubstantiated. To date, the
      cardiovascular, central nervous and immune systems are the most common
      therapeutic categories cited in the literature and other than those, examples are
      very limited. Although many herbal drugs have good safety profiles, it must be
      borne in mind that herbal supplements are intended to be taken over an extended
      period of time, which provides the opportunity for enzyme induction and other
      mechanisms of interaction to take effect.

PMID- 14640774
TI  - Rise in psychotropic drug prescribing in children in the UK : an urgent public
      health issue.

PMID- 14640775
TI  - Is antibiotic resistance in cutaneous propionibacteria clinically relevant? :
      implications of resistance for acne patients and prescribers.
AB  - It is well recognized that some patients with acne do not respond adequately to
      antibiotic therapy. It is important to distinguish antibiotic recalcitrant acne
      which we would suggest represents acne that shows a diminished response to
      treatment irrespective of the cause as opposed to 'antibiotic-resistant acne'
      which is acne that is less responsive to treatment as a direct consequence of
      skin colonization with resistant propionibacteria. Here we show that antibiotic
      resistant acne is not just a theoretical possibility but a real phenomenon that
      could have important consequences for patients and prescribers. The relationship
      between skin colonization by antibiotic-resistant propionibacteria and treatment
      outcomes is a complex one that is explained at the follicular level by
      physiological differences affecting local drug concentrations. A systematic
      review of the literature on antibiotic-resistant propionibacteria revealed
      methodological shortcomings in studies of their prevalence and a paucity of
      evidence on their clinical significance. Despite the elucidation of resistance
      mechanisms in cutaneous propionibacteria, our continuing inability to distinguish
      between strains of Propionibacterium acnes means that we still do not fully
      understand how resistance spreads, although person-to-person transfer is most
      likely. Finally, we present a decision tree for acne management in an era of
      prudent antimicrobial prescribing that provides an alternative to existing
      treatment algorithms by placing topical retinoids and not antibiotics at the
      cornerstone of acne management.

PMID- 14640776
TI  - Psychiatric and psychological co-morbidity in patients with dermatologic
      disorders: epidemiology and management.
AB  - Psychiatric and psychological factors play an important role in at least 30% of
      dermatologic disorders. In many cases the impact of the skin disorder upon the
      quality of life is a stronger predictor of psychiatric morbidity than the
      clinical severity of the disorder as per physician ratings. Furthermore, in
      certain disorders such as acne and psoriasis, the psychiatric co-morbidity, which
      can be associated with psychiatric emergencies such as suicide, is an important
      measure of the overall disability experienced by the patient. The severity of
      depression and increased suicide risk are not always directly correlated with the
      clinical severity of the dermatologic disorder. Consideration of psychiatric and
      psychosocial factors is important both for the management, and for some aspects
      of secondary and tertiary prevention of a wide range of dermatologic disorders.
      It is useful to use a biopsychosocial model which takes into account the
      psychological (e.g. psychiatric comorbidity such as major depression and the
      impact of the skin disorder on the psychological aspects of quality of life) and
      social (e.g. impact upon social and occupational functioning) factors, in
      addition to the primary dermatologic factors, in the management of the patient.
      Some dermatology patients are likely to benefit from psychotherapeutic
      interventions and psychotropic agents for the management of the psychosocial
      comorbidity, in addition to the standard dermatologic therapies for their skin
      disorder.

PMID- 14640777
TI  - Racial (ethnic) differences in skin properties: the objective data.
AB  - Racial (ethnic) differences in skin properties may explain racial disparities
      seen in dermatologic disorders and provide insight into appropriate differences
      in the management of these disorders. However, racial differences in skin have
      been minimally investigated by objective methods and the data are often
      contradictory. Objective methods studied include transepidermal water loss
      (TEWL), water content (WC), corneocyte variability, blood vessel reactivity,
      elastic recovery/extensibility, pH gradient, lipid content, surface microflora,
      microscopic evaluation of mast cell granules, and confocal microscopy. The
      majority of the evidence (six out of eight studies) indicates that TEWL is
      greater in Black skin compared with White skin. TEWL measurements of Asian skin
      are inconclusive as they have been found to be equal to Black skin and greater
      than Caucasian skin, equal to Caucasian skin, and less than all other ethnic
      groups in different studies. Racial differences in WC, as measured by resistance,
      capacitance, conductance and impedance, are also inconclusive as the data are
      contradictory. While the evidence regarding corneocyte desquamation is minimal,
      one clinically provocative observation is that Blacks have a 2.5 times greater
      spontaneous desquamation rate compared with Caucasians and Asians, possibly
      accounting for an increased frequency of xerosis seen clinically in Blacks. With
      regards to blood vessel reactivity, studies can not be compared to each other
      because each uses different vasoactive substances. However, each study, except
      for one study comparing Hispanics and Whites, and another comparing Japanese and
      German women, reveal some degree of racial variation in blood vessel reactivity.
      It has been demonstrated that the pH of Black skin is less than White skin;
      however, the studies that have demonstrated this have done so under different
      skin conditions and on different anatomic sites. Racial differences in lipid
      content are inconclusive. Additionally, there is insufficient and conflicting
      evidence to make conclusions regarding racial differences in skin biomechanics
      and skin microflora. Microscopic evaluation reveals that Black skin contains
      larger mast cell granules, and differences in stuctural properties and enzymes of
      mast cells compared with White skin, possibly accounting for differences in
      pruritus experienced by the individuals of these racial groups. There exists
      substantial evidence to support that Black skin has a higher TEWL, variable blood
      vessel reactivity, decreased skin surface pH, and larger mast cell granules
      compared with White skin. Although some deductions have been made about Asian and
      Hispanic skin, further evaluation needs to be done. Differences in WC, corneocyte
      desquamation, elastic recovery/extensibility, lipid content and skin microflora,
      although statistically significant, are inconclusive.

PMID- 14640773
TI  - Safety of new phosphate binders for chronic renal failure.
AB  - Phosphate (Pi) retention is a common problem in patients with chronic kidney
      disease, particularly in those who have reached end-stage renal disease (ESRD).
      In addition to causing secondary hyperparathyroidism and renal osteodystrophy,
      recent evidence suggests that, in ESRD patients, high serum phosphorus
      concentration and increased calcium and phosphorous (Ca x P) product are
      associated with vascular and cardiac calcifications and increased mortality.
      Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to
      restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi
      binders is currently the primary treatment for Pi retention in patients with
      ESRD. The use of large doses of calcium-containing Pi binders along with
      calcitriol administration may contribute to over-suppression of parathyroid
      hormone secretion and adynamic bone disease as well as to a high incidence of
      vascular calcifications. When used in patients with impaired renal function,
      aluminium salts were found to accumulate in bone and other tissues, resulting in
      osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi
      binder can reduce serum phosphorus concentration and is associated with a
      significantly lower incidence of hypercalcaemia, while maintaining the ability to
      suppress parathyroid hormone production. An additional benefit of sevelamer is
      its ability to lower low density lipoprotein-cholesterol and total cholesterol
      levels. Sevelamer attenuates the progression of vascular calcifications in
      haemodialysis patients, which may lead to lower mortality. The use of sevelamer
      in non-dialysed patients might aggravate metabolic acidosis, common in these
      patients. Several other calcium-free Pi binders are in development. Lanthanum
      carbonate has shown significant promise in clinical trials in ESRD patients.
      Magnesium salts do not offer a significant advantage over currently available Pi
      binders. Their use is restricted to patients receiving dialysis since excess
      magnesium must be removed by dialysis. Iron-based compounds have shown variable
      efficacy in short-term clinical trials in small numbers of haemodialysis
      patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals
      but have not been studied in humans. Major safety issues include absorption of
      the metal component with possible tissue accumulation and toxicity.

PMID- 14640778
TI  - Cost of medications in patients admitted to a burn center.
AB  - BACKGROUND: Few studies have examined the cost associated with burn patients, and
      those which have been conducted have generally focused on overall hospitalization
      costs associated with these patients. No studies to date have examined the
      overall drug utilization and costs of medications used in the treatment of burn
      patients. OBJECTIVE: To describe the pattern of drug utilization and associated
      costs for the treatment of patients admitted to the Ross Tilley Burn Centre at
      Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
      METHODS: A retrospective chart review was conducted based on the medical records
      of 30 adult patients (>18 years old) consecutively admitted to the burn center
      between 1 August 1999 and 30 September 1999. Charts were examined to determine
      drugs administered, doses and duration of use. Medications administered in the
      operating room were excluded from the analysis. Drug costs were calculated using
      hospital acquisition costs (1999 Canadian dollars [$Can]) and medications were
      categorized by pharmacological class according to the American Hospital Formulary
      Service. Demographic information for the patients was extracted from the burn
      center's database. The economic analysis was performed from the perspective of
      the hospital burn center. A descriptive statistical analysis was completed for
      all variables; the Pearson correlation coefficient was used to examine the
      relationship between certain variables. A sensitivity analysis was conducted to
      examine the impact of patient subgroups on certain variables RESULTS: Of the 28
      patients included in the analysis, 19 were admitted with acute burn injuries, two
      with toxic epidermal necrolysis and seven for post-burn reconstructive surgery.
      Patients admitted for acute burns or toxic epidermal necrolysis had the highest
      associated drug costs. On average, patients received 13 different drugs
      representing four different pharmacological categories. The mean daily drug cost
      per patient was $Can18.39 and the mean expenditure per admission was $Can792.97.
      Opioid analgesics and sedatives accounted for the largest expenditure (50.9%),
      followed by anti-infective agents (23.4%). For patients admitted with acute
      burns, there was a good correlation between daily drug costs and mortality risk
      (r = 0.82, p < 0.001). The findings from this study group were used to
      extrapolate annual expenses for medications in the burn center and these were
      estimated to exceed $Can280 300 in 2003. CONCLUSION: The findings of this
      retrospective analysis serve to elucidate the patterns of drug utilization within
      a population of burn patients and confirm the significant impact of a burn center
      on an institution's drug expenditure.

PMID- 14640779
TI  - Chromosomal aberrations and micronuclei in lymphocytes of breast cancer patients
      after an accident during radiotherapy with 8 MeV electrons.
AB  - In February 2001 a radiation accident occurred in a radiotherapy unit of an
      oncology hospital in Poland. Five breast cancer patients undergoing radiotherapy
      received a single high dose of 8 MeV electrons. The exact doses are not known,
      but they were heterogeneous and may have reached about 100 Gy. To assess whether
      such exposure would be detectable in peripheral blood lymphocytes, chromosomal
      aberrations and micronuclei were analyzed in lymphocytes from the accident
      patients and compared to values for lymphocytes from 10 control patients who were
      not involved in the accident but who received similar radiotherapy treatments.
      Lymphocytes were harvested for analysis of chromosomal aberrations at three
      different culture times to determine whether heavily damaged cells reached
      mitosis with a delay. There was no effect of harvest time on the frequencies of
      chromosomal aberrations, indicating that there was no delay of heavily damaged
      cells in entering mitosis. A good correlation was observed between micronuclei
      and chromosomal aberrations. In lymphocytes from three of the accident patients,
      significantly enhanced frequencies of both aberrations and micronuclei were
      found. The great individual variability observed in the frequency of cytogenetic
      damage in lymphocytes from both control and accident patients precluded the
      unambiguous identification of all accident patients.

PMID- 14640780
TI  - Assessment of proton microbeam analysis of 11B for quantitative microdistribution
      analysis of boronated neutron capture agents in biological tissues.
AB  - The (11)B(p,alpha)(8)Be* nuclear reaction was assessed for its ability to
      quantitatively map the in vivo subcellular distribution of boron within
      gliosarcomas treated with a boronated neutron capture therapy agent. Intracranial
      9L gliosarcomas were produced in Fischer 344 rats. Fourteen days later, the
      majority of the rats were treated with f-boronophenylalanine and killed humanely
      30 or 180 min after intravenous injection. Freeze-dried tumor cryosections were
      imaged using the (11)B(p,alpha)(8)Be* nuclear reaction and proton microbeams
      obtained from the nuclear microprobe at Lawrence Livermore National Laboratory.
      The (11)B distributions within cells could be imaged quantitatively with spatial
      resolutions down to 1.5 microm, minimum detection limits of 0.8 mg/kg, and
      acquisition times of several hours. These capabilities offer advantages over
      alpha-particle track autoradiography, electron energy loss spectroscopy, and
      secondary ion mass spectrometry (SIMS) for quantification of (11)B in tissues.
      However, the spatial resolution, multi-isotope capability, and analysis times
      achieved with SIMS are superior to those achieved with (11)B(p,alpha)(8)Be*
      analysis. When accuracy in quantification is crucial, the (11)B(p,alpha)(8)Be*
      reaction is well suited for assessing the microdistribution of (11)B. Otherwise,
      SIMS may well be better suited to image the microdistribution of boron associated
      with neutron capture therapy agents in biological tissues.

PMID- 14640781
TI  - In vivo postirradiation protection by a vitamin E analog, alpha-TMG.
AB  - The water-soluble vitamin E derivative alpha-TMG is an excellent radical
      scavenger. A dose of 600 mg/kg TMG significantly reduced radiation clastogenicity
      in mouse bone marrow when administered after irradiation. The present study was
      aimed at investigating the radioprotective effect of postirradiation treatment
      with alpha-TMG against a range of whole-body lethal (8.5-12 Gy) and sublethal (1
      5 Gy) doses of radiation in adult Swiss albino mice. Protection against lethal
      irradiation was evaluated from 30-day mouse survival and against sublethal doses
      was assessed from micronuclei and chromosomal aberrations in the bone marrow 24 h
      after irradiation. An intraperitoneal injection of 600 mg/kg TMG within 10 min of
      lethal irradiation increased survival, giving a dose modification factor (DMF) of
      1.09. TMG at doses of 400 mg/kg and 600 mg/kg significantly reduced the
      percentage of aberrant metaphases, the different types of aberrations, and the
      number of micronucleated erythrocytes. DMFs of 1.22 and 1.48 for percentage
      aberrant metaphases and 1.6 and 1.98 for micronuclei were obtained for 400 mg/kg
      and 600 mg/kg TMG, respectively. No drug toxicity was observed at these doses.
      The effectiveness of TMG when administered postirradiation suggests its possible
      utility for protection against unplanned radiation exposures.

PMID- 14640782
TI  - Effects of single-dose irradiation on bronchial epithelium: a comparison of BEAS
      2B cell monolayers, human organ cultures, and Goettinger minipigs.
AB  - To assess the effects of radiation on bronchial epithelium, BEAS 2B cells
      cultured as monolayers and human bronchial epithelium cultured as organ cultures
      were exposed to single doses of 0, 10 and 30 Gy. The lactate dehydrogenase in the
      supernatant of the BEAS 2B cells increased markedly 24 h after irradiation,
      whereas in the organ cultures only a minor increase was found after 48 h. The
      nucleosomes in the supernatant of the BEAS 2B cells showed a massive increase in
      response to irradiation, whereas in the organ cultures no change could be seen.
      The number of BEAS 2B cells was dramatically diminished after 96 h, whereas in
      the organ cultures a smaller decrease was observed no earlier than 21 days after
      irradiation. To assess the effects of brachytherapy in bronchial epithelium in
      vivo, brachytherapy with 30 Gy was performed in Goettinger minipigs, and
      histological sections of the bronchi were analyzed for morphological alterations
      and cell numbers. After 2 weeks, only slight cell damage was observable, and
      after 3 weeks, moderate morphological changes and decreased cell numbers were
      found. However, after 8 weeks, the epithelium had nearly regained its normal
      structure. We conclude that the bronchial epithelium has a remarkably high
      radioresistance and that organ cultures, but not monolayers of BEAS 2B cells,
      reflect the effects of radiation in vivo.

PMID- 14640783
TI  - Inflammatory reaction and changes in expression of coagulation proteins on lung
      endothelial cells after total-body irradiation in mice.
AB  - Inflammatory reaction is a classical feature of radiation exposure, and
      pneumonitis is a dose-limiting complication in the handling of hematological
      disorders treated with total-body irradiation. In the present study, we first
      evaluated the inflammatory response in C57BL6/J mice exposed to lethal doses of
      gamma rays treated with antibiotics or not. Both interleukin 6 and KC (also known
      as Gro1) were increased in the plasma 10 to 18 days after radiation exposure,
      independent of bacterial infection, whereas fibrinogen release was linked to a
      bacterial infection. Furthermore, both Il6 and KC were increased in the lungs of
      irradiated mice. Our second objective was to characterize the endothelial cell
      changes in the lungs of total-body-irradiated mice. For this purpose, a
      quantitative RT-PCR was used to determine the expression of genes involved in
      inflammatory and coagulation processes. We found that the adhesion molecules P
      selectin and platelet endothelial cell adhesion molecule 1 were up-regulated,
      whereas E-selectin remained unchanged. Tissue factor expression was up-regulated
      as well, and thrombomodulin gene expression was down-regulated. The investigation
      by immunohistochemistry of adhesion molecules confirmed the increase in the basal
      expression of both P-selectin and platelet endothelial cell adhesion molecule 1
      on pulmonary endothelial cells. All together, our results suggest the involvement
      of endothelial cells in the development of radiation-induced inflammatory and
      thrombotic processes.

PMID- 14640784
TI  - Nitric oxide voltammetric measurements in the rat brain after gamma irradiation.
AB  - The effects of a lethal gamma irradiation were investigated on cerebral NO-ergic
      system by using a voltammetric method in freely moving rats. It is reported that
      the cortical NO concentration increases right from the end of the radiation
      exposure (15 Gy) and reaches a maximal magnitude (+120%) 24 h later. A dose
      effect relationship from 2 to 15 Gy for gamma-ray exposure has also been
      observed. The effects, obtained with either an NO synthase inhibitor nonselective
      for the different NO synthase isoforms or an NO synthase inhibitor selective for
      the constitutive isoform, suggest that the radiation-induced increase in NO is
      likely to be dependent on the inducible NO synthase isoform. Moreover,
      experiments performed under ex vivo conditions showed that the cortical mRNA
      level for Ca(++)-independent NO synthase, the brain NOS activity, and urinary
      nitrites/nitrates increased significantly 24 h after gamma-ray exposure. These
      results demonstrate that a supralethal whole-body irradiation alters the NO-ergic
      pathways. The increase in NO obtained under such conditions might constitute a
      good index of central nervous system radiosensitivity during the acute phase of
      the radiation syndrome.

PMID- 14640785
TI  - Adaptation of the dichlorofluorescein assay for detection of radiation-induced
      oxidative stress in cultured cells.
AB  - The oxidation of 2'7'-dichlorofluorescin (DCFH) to 2'7'-dichlorofluorescein
      (DCF), a fluorescent DCFH oxidation product, is a highly sensitive indicator that
      is used to measure oxidative stress in cells. In the present study, a DCF assay
      has been adapted to quantify oxidative stress in human breast epithelial cell
      cultures after exposure to gamma rays. The results demonstrate that the
      sensitivity and specificity of the DCF assay is strongly influenced by the timing
      of DCFH diacetate (DCFH-DA) substrate loading in relation to radiation exposure
      and by the matrix in which the cells were loaded with DCFH-DA substrate. Under
      the conditions optimized in this study, the DCF assay is capable of detecting
      increased DCFH oxidation in cell cultures irradiated with gamma rays at a dose as
      low as 1.5 cGy. The increase in fluorescence was directly proportional to the
      radiation dose, which ranged from 0 to 2 Gy, and a minimal level of fluorescence
      was observed in sham-irradiated cells. These results indicate that the DCF assay
      optimized in this study is highly sensitive, linear and specific for measuring
      oxidative stress in irradiated cells.

PMID- 14640786
TI  - Radiation-induced cyclooxygenase 2 up-regulation is dependent on redox status in
      prostate cancer cells.
AB  - Cyclooxygenase 2 (COX2) is the inducible isozyme of COX, a key enzyme in
      arachidonate metabolism and the conversion of arachidonic acid (AA) to
      prostaglandins (PGs) and other eicosanoids. Previous studies have demonstrated
      that the COX2 protein is up-regulated in prostate cancer cells after irradiation
      and that this results in elevated levels of PGE(2). In the present study, we
      further investigated whether radiation-induced COX2 up-regulation is dependent on
      the redox status of cells from the prostate cancer cell line PC-3. l-Buthionine
      sulfoximine (BSO), which inhibits gamma glutamyl cysteine synthetase (gammaGCS),
      and the antioxidants alpha-lipoic acid and N-acetyl-l-cysteine (NAC) were used to
      modulate the cellular redox status. BSO decreased the cellular GSH level and
      increased cellular reactive oxygen species (ROS) in PC-3 cells, whereas alpha
      lipoic acid and NAC increased the GSH level and decreased cellular ROS. Both
      radiation and the oxidant H(2)O(2) had similar effects on COX2 up-regulation and
      PGE(2) production in PC-3 cells, suggesting that radiation-induced COX2 up
      regulation is secondary to the production of ROS. The relative increases in COX2
      expression and PGE(2) production induced by radiation and H(2)O(2) were even
      greater when PC-3 cells were pretreated with BSO. When the cells were pretreated
      with alpha-lipoic acid or NAC for 24 h, both radiation- and H(2)O(2)-induced COX2
      up-regulation and PGE(2) production were markedly inhibited. These results
      demonstrate that radiation-induced COX2 up-regulation in prostate cancer cells is
      modulated by the cellular redox status. Radiation-induced increases in ROS levels
      contribute to the adaptive response of PC-3 cells, resulting in elevated levels
      of COX2.

PMID- 14640787
TI  - Differential sensitivity to short-chain ceramide analogues of human intestinal
      carcinoma cells grown in tumor spheroids versus monolayer culture.
AB  - The cytotoxic activity of short-chain (C(2)) ceramide was evaluated in human
      intestinal carcinoma cells grown as multicellular tumor spheroids versus the same
      cells cultured as monolayers under closely comparable conditions. A decrease in
      cell number was seen in monolayer cultures of HT-29, Caco-2, and HRT-18 cells,
      with an EC(50) (concentration for half-maximal toxicity) of between 13 and 23
      microM. However, when the same cells were grown in the multicellular spheroid
      format, C(2) was markedly less potent in reducing cell number, with an EC(50) of
      between 44 and 63 microM, representing a 1.9- to 4.9-fold decrease in its
      potency. The chemotherapeutic agents 5-fluorouracil and cisplatin were equally
      potent against spheroids and monolayer cultures, indicating that although drug
      access is a problem in conventionally grown tumor spheroids it is not a problem
      for spheroids grown under the conditions used in this study. Our results suggest
      that although ceramide is capable of inducing cell death in intestinal carcinoma
      cells grown in spheroid culture, its cellular toxicity is constrained by
      influences that are independent of drug access and may be the consequence of the
      altered cellular relationships. Carcinoma cell populations show an intrinsically
      decreased responsiveness to the effects of ceramide when they are grown in a
      three-dimensional culture format.

PMID- 14640788
TI  - A simple method using beta-globin polymerase chain reaction for the species
      identification of animal cell lines--a progress report.
AB  - Continuous cell lines are widely used in cell biology and serve as model systems
      in basic and applied research. Fundamental requirements for the use of cell lines
      are a well-identified origin and the exclusion of cross-contamination by
      prokaryotic or eukaryotic cells. Because the cross-contamination of one cell line
      with another cell line may occur in a concealed manner, special emphasis must be
      taken to (1) prevent such an "accident" and (2) monitor regularly the identity of
      the cell line(s) in use. Apart from human cell lines, mouse-, rat-, and hamster
      derived cell lines are used in basic cell culture and biotechnology. We
      established a polymerase chain reaction (PCR) assay to detect and confirm the
      species origin for these species and to detect interspecies cross-contamination.
      Our PCR method is based on oligonucleotide primers annealing to specific
      sequences in the beta-globin gene, which were designed to amplify one
      deoxyribonucleic acid (DNA) segment only per analyzed sample. We confirmed the
      species identity of 82 cell lines as human, mouse, rat, and Syrian hamster by
      beta-globin PCR. The DNAs from eight additional cell lines of less frequently
      used species were not amplified with the primers chosen. Cross-contamination of 5
      10% of either mouse or rat DNA was detectable. One species-specific primer pair
      was sufficient for confirmation of the expected species, and for identification
      of an unknown cell line the combination of two or more primer pairs is suggested.
      Our PCR assay represents a powerful, fast, easy, robust, and inexpensive method
      for speciation and does not need any elaborate sequencing or computer-based
      analysis system.

PMID- 14640790
TI  - Education and training for radiation scientists: radiation research program and
      American Society of Therapeutic Radiology and Oncology Workshop, Bethesda,
      Maryland, May 12-14, 2003.
AB  - Current and potential shortfalls in the number of radiation scientists stand in
      sharp contrast to the emerging scientific opportunities and the need for new
      knowledge to address issues of cancer survivorship and radiological and nuclear
      terrorism. In response to these challenges, workshops organized by the Radiation
      Research Program (RRP), National Cancer Institute (NCI) (Radiat. Res. 157, 204
      223, 2002; Radiat. Res. 159, 812-834, 2003), and National Institute of Allergy
      and Infectious Diseases (NIAID) (Nature, 421, 787, 2003) have engaged experts
      from a range of federal agencies, academia and industry. This workshop, Education
      and Training for Radiation Scientists, addressed the need to establish a
      sustainable pool of expertise and talent for a wide range of activities and
      careers related to radiation biology, oncology and epidemiology. Although
      fundamental radiation chemistry and physics are also critical to radiation
      sciences, this workshop did not address workforce needs in these areas. The
      recommendations include: (1) Establish a National Council of Radiation Sciences
      to develop a strategy for increasing the number of radiation scientists. The
      strategy includes NIH training grants, interagency cooperation,
      interinstitutional collaboration among universities, and active involvement of
      all stakeholders. (2) Create new and expanded training programs with sustained
      funding. These may take the form of regional Centers of Excellence for Radiation
      Sciences. (3) Continue and broaden educational efforts of the American Society
      for Therapeutic Radiology and Oncology (ASTRO), the American Association for
      Cancer Research (AACR), the Radiological Society of North America (RSNA), and the
      Radiation Research Society (RRS). (4) Foster education and training in the
      radiation sciences for the range of career opportunities including radiation
      oncology, radiation biology, radiation epidemiology, radiation safety,
      health/government policy, and industrial research. (5) Educate other scientists
      and the general public on the quantitative, basic, molecular, translational and
      applied aspects of radiation sciences.

PMID- 14640791
TI  - The parameter-free track structure model of Scholz and Kraft for heavy-ion cross
      sections.
AB  - The "parameter-free", "local effects" theory of Scholz and Kraft is an extension
      to mammalian cells of the theory of RBE for dry enzymes and viruses of Butts and
      Katz. Its claim for parameter freedom has been challenged elsewhere. Here we
      examine its conceptual base and find errors in its use of the physical concept of
      cross section and its neglect of the radiobiological relationship between target
      size and radiosensitivity in evaluating the radiation damage to "point targets".

PMID- 14640793
TI  - Incidence of female breast cancer among atomic bomb survivors, Hiroshima and
      Nagasaki, 1950-1990.
AB  - An incidence survey of the Life Span Study (LSS) population found 1093 breast
      cancers among 1059 breast cancer cases diagnosed during 1950-1990. As in earlier
      breast cancer surveys of this population, a linear and statistically highly
      significant radiation dose response was found. In the analysis, particular
      attention was paid to modification of radiation dose response by age at exposure
      (e) and attained age (a). Dose-specific excess relative risk (ERR(1Sv)) decreased
      with increasing values of e and a. A linear dose-response model analysis, with e
      and a as exponential age modifiers, did not conclusively discriminate between the
      two variables as modifiers of dose response. A modified isotonic regression
      approach, requiring only that ERR(1Sv) be monotonic in age, provides a fresh
      perspective indicating that both e and a are important modifiers of dose
      response. Exposure before age 20 was associated with higher ERR(1Sv) compared to
      exposure at older ages, with no evidence of consistent variation by exposure age
      for ages under 20. ERR(1Sv) was observed to decline with increasing attained age,
      with by far the largest drop around age 35. Possible explanations for these
      observations are discussed, along with research approaches that might provide
      more information.

PMID- 14640792
TI  - Mechanistic models for radiation carcinogenesis and the atomic bomb survivor
      data.
AB  - Recently, Heidenreich et al. (Radiat. Res., 158, 607-617, 2002) suggested that
      the Radiation Effects Research Foundation (RERF) A-bomb survivor cohort study is
      not large enough to discriminate between various possible carcinogenic
      mechanisms. At least with the current follow-up, this is true to some extent, but
      I think the specific issues are rather different than they suggest. In
      particular, I do not think it is true-as they further indicate-that various
      models fit the data about equally well while estimating very different patterns
      of excess risk, which would imply that these patterns cannot be reasonably well
      characterized. I will point to specific criticisms of their approach to the data
      and offer some more general comments on mechanistic modeling approaches. Although
      there are important distinctions, I suggest on a very optimistic note that the
      two major approaches may be converging, and soon the main differences may not be
      in the assumptions made but in the aims of the modeling.

PMID- 14640795
TI  - Micronucleus frequency is increased in peripheral blood lymphocytes of nuclear
      power plant workers.
AB  - Nuclear power plant workers are exposed to ionizing radiation at relatively low
      doses and for prolonged periods of time. To investigate the extent of genetic
      damage in these workers, a group of 133 nuclear power plant workers and 39
      healthy controls were compared using the cytokinesis-block micronucleus assay.
      The frequency of micronuclei was significantly increased in peripheral
      lymphocytes of nuclear power plant workers (20.5 +/- 9.7% compared to 13.7 +/-
      5.9%). A significant dose-response relationship was observed between micronucleus
      (MN) frequency and both the accumulated dose and the duration of employment (P <
      0.01 for both variables after adjusting for age, gender and cigarette smoking)
      with an evident leveling off for exposures over 200 mSv. Accumulated dose and
      duration of employment were significantly correlated but exerted independent
      effects on MN frequency. For non-occupational parameters, age was significantly
      associated with the frequency of micronuclei, while gender was not. Smoking habit
      showed no overall effect, whereas increased chromosome damage was evident in
      smokers of more than 20 cigarettes per day. In conclusion, a dose-related
      association between MN frequency and exposure to ionizing radiation was evident
      in nuclear power plant workers, encouraging the application of the cytokinesis
      block micronucleus assay in biomonitoring studies of human populations with
      prolonged exposure to ionizing radiation.

PMID- 14640794
TI  - Site-specific cancer incidence and mortality after cerebral angiography with
      radioactive thorotrast.
AB  - Few opportunities exist to evaluate the carcinogenic effects of long-term
      internal exposure to alpha-particle-emitting radionuclides. Patients injected
      with Thorotrast (thorium-232) during radiographic procedures, beginning in the
      1930s, provide one such valuable opportunity. We evaluated site-specific cancer
      incidence and mortality among an international cohort of 3,042 patients injected
      during cerebral angiography with either Thorotrast (n = 1,650) or a
      nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized
      incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and
      Sweden) were estimated and relative risks (RR), adjusted for population, age and
      sex, were generated with multivariate statistical modeling. For U.S. patients,
      comparable procedures were used to estimate standardized mortality ratios (SMR)
      and RR, representing the first evaluation of long-term, site-specific cancer
      mortality in this group. Compared with nonexposed patients, significantly
      increased risks in Thorotrast patients were observed for all incident cancers
      combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer
      mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident
      cancers were above expectation, with large excesses seen for cancers of the
      liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other
      than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with
      time since angiography (P < 0.001) and was threefold at 40 or more years;
      significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative
      dose of radiation was associated with an increasing risk of all incident cancers
      taken together and with cancers of the liver, gallbladder, and peritoneum and
      other digestive sites; similar findings were observed for U.S. cancer mortality.
      A marginally significant dose response was observed for the incidence of pancreas
      cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship
      between Thorotrast and increased cancer incidence at sites of Thorotrast
      deposition and suggests a possible association with pancreas cancer. After
      injection with >20 ml Thorotrast, the cumulative excess risk of cancer incidence
      remained elevated for up to 50 years and approached 97%. Caution is needed in
      interpreting the excess risks observed for site-specific cancers, however,
      because of the potential bias associated with the selection of cohort
      participants, noncomparability with respect to the internal or external
      comparison groups, and confounding by indication. Nonetheless, the substantial
      risks associated with liver cancer and leukemia indicate that unique and
      prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic
      risks.

PMID- 14640796
TI  - Current and recollected perceptions of family relationships: the social relations
      model approach applied to members of three generations.
AB  - Data from 81 three-generation families (comprising 567 participants) were
      analyzed to assess perceptions of current-family and family-of-origin
      relationships. The dimensions studied (Restrictiveness, Justice, Affection, and
      Trust) were derived from the family systems theories as developed by Boszormenyi
      Nagy (I. Boszormenyi-Nagy & B. R. Krasner, 1986; I. Boszormenyi-Nagy & G. Spark,
      1984; I. Boszormenyi-Nagy & D. N. Ulrich, 1981) and Stierlin (H. Stierlin, 1974,
      1978; H. Stierlin, I. Rucker-Embden, N. Wetzel, & M. Wirsching, 1980). The social
      relations model (SRM) was used to disentangle the perception scores into
      characteristics of the perceiver (actor component), the target (partner
      component), and the family as a whole. For both current-family and family-of
      origin relationships, significant variances of actor as well as family components
      were found. Empirical evidence for an association between current-family and
      (mother's) family-of-origin components was only found on the dimension of
      Restrictiveness. Clear differences were found between the means of current-family
      and family-of-origin perceptions, which could be explained by differences between
      current and past SRM components.

PMID- 14640797
TI  - Intergenerational relationships in young adulthood and their life course, mental
      health, and personality correlates.
AB  - To evaluate effects of life-course events and experiences of young adults, as
      well as personality and mental-health history on intergenerational relationships
      in young adulthood, the authors examined dyadic relationship data drawn from a
      sample of more than 900 New Zealand 26-year-olds and their mothers and fathers.
      Results indicated that intergenerational relations were more positive when young
      adults were childless, not unemployed, married, and living away from home, but
      these factors did not interact with family relationship history in predicting
      relationship outcomes. Intergenerational relationships were less positive when
      children scored low on positive emotionality and constraint and high on negative
      emotionality and mental disorders, though these attributes did not account for
      the effect of life-course factors. Results are discussed in terms of the openness
      of the parent-child relationship in adulthood to further development.

PMID- 14640798
TI  - Perceived parental differential treatment in middle adulthood: curvilinear
      relations with individuals' experienced relationship quality to sibling and
      parents.
AB  - Guided by predictions from equity theory and the self-esteem maintenance model,
      links between perceptions of current parental differential treatment and the
      perceiver's experienced relationship quality with sibling and parents were
      analyzed in a sample of 1,020 adult (middle-aged) offspring. Participants rated
      how often they and a sibling receive parental recognition, nurture, and demands
      for filial responsibility. In addition, they indicated their emotions and
      behaviors toward sibling and parents. Data analyses showed that an individual's
      experienced relationship with sibling was best when both were treated equally and
      diminished with increasing favoritism or disfavoritism. Experienced relationship
      with parents was best when participants were favored a bit; the relationship
      worsened when participants were disfavored and worsened only slightly when they
      were extremely favored. Results are discussed regarding mediating processes and
      implications for practical applications.

PMID- 14640799
TI  - Family processes within three-generation households and adolescent mothers'
      satisfaction with father involvement.
AB  - This investigation used a family systems perspective to examine how family
      dynamics within 3-generation households were associated with mothers'
      satisfaction with father involvement. The participants were low-income African
      American adolescent mothers (n=148) and grandmothers recruited at delivery and
      followed over 6 months. The overall model explained 68% of the variance in
      satisfaction with father involvement. Fathers who were involved with caregiving
      activities had positive relationships with adolescent mothers and grandmothers.
      Grandmothers served as gatekeepers; when grandmothers reported positive
      relationships with the 2 young parents, adolescent mothers reported positive
      relationships with their male partners. Mothers who reported positive partner
      relationships also reported high parenting efficacy and satisfaction with father
      involvement. Efforts to increase paternal involvement should focus on role
      clarification for grandmothers and fathers and on parenting activities for
      mothers and fathers, regardless of their romantic relationship.

PMID- 14640801
TI  - Parental problem drinking and children's adjustment: attachment and family
      functioning as moderators and mediators of risk.
AB  - Children's perceived attachments with parents, and family cohesion and
      adaptability were examined as predictors, mediators, and moderators in the
      parental problem drinking-child outcomes link. A total of 216 6- to 12-year-olds
      (110 boys, 106 girls) participated. Data were obtained from children and their
      mothers, fathers, and teachers. A higher level of family cohesion and
      adaptability functioned as (a) a robust protective factor against adjustment and
      cognitive difficulties otherwise associated with problem drinking and (b) a
      mediator of adjustment problems. Children's perceptions of attachments to mothers
      and fathers were consistent predictors of behavioral, social, and cognitive
      problems and further moderated relations between problem drinking and child
      functioning. The results support that child-parent and family functioning
      variables act as either pathways and/or vulnerability and protective factors for
      children exposed to a high-risk environment.

PMID- 14640800
TI  - Linking changes in whole family functioning and children's externalizing behavior
      across the elementary school years.
AB  - This study used observational assessments of 57 2-parent families working and
      playing together when their eldest child was in kindergarten and again in Grade 4
      to identify distinct patterns of family functioning derived from structural
      family systems theory for (a) cohesive, (b) separate, and (c) triangulated
      families. Little consistency in family type from early to middle childhood was
      indicated. No significant mean differences were found in teacher reports of
      children's externalizing behavior in their Grade 1 classrooms for children in
      cohesive or triangulated families. Fourth graders in triangulated families were
      seen as more aggressive at school than were their peers in cohesive or separate
      families. Changes in observed family functioning across a 4-year period
      (kindergarten to Grade 4) were also systematically linked to changes in teachers'
      ratings of children's externalizing behavior from Grades 1 to 4.

PMID- 14640802
TI  - The role of adolescent friends, romantic partners, and siblings in the emergence
      of the adult antisocial lifestyle.
AB  - This study investigated the contribution of social processes in boys' adolescent
      relationships in 3 key domains--same-sex friends, cross-sex romantic partners,
      and younger siblings--to continued association with delinquent peers in young
      adulthood and, therefore, to continuance of an antisocial lifestyle. It was
      hypothesized that levels of negative interaction and antisocial talk observed
      during problem-solving discussions would be associated across the 3 domains. The
      influences of negative interactions and antisocial talk in the adolescent
      relationships on young-adult delinquent peer association were compared in 2
      mediational models. It was posited that antisocial talk would be more predictive
      of continued association with delinquent peers than would negative interactions.
      Hypotheses were tested on an at-risk sample of young men (the Oregon Youth
      Study). Findings were generally in keeping with the hypotheses.

PMID- 14640803
TI  - Alliance and dropout in family therapy for adolescents with behavior problems:
      individual and systemic effects.
AB  - This study examined the relationship between alliance and retention in family
      therapy. Alliance was examined at the individual (parent and adolescent) and
      family levels (within-family differences). Participants were 34 families who
      received functional family therapy for the treatment of adolescent (aged 12-18
      years) behavior problems. Families were classified as treatment dropouts (n=14)
      or completers (n=20). Videotapes of the first sessions were rated to identify
      parent and adolescent alliances with the therapist. Results demonstrated that
      individual parent and adolescent alliances did not predict retention. However, as
      hypothesized, dropout cases had significantly higher unbalanced alliances (parent
      minus adolescent) than did completer cases. These findings highlight the
      importance of alliances in functional family therapy and suggest that how the
      alliance operates in conjoint family therapy may be a function of systemic rather
      than of individual processes.

PMID- 14640804
TI  - Mediators of the relation between maternal depressive symptoms and child
      internalizing and disruptive behavior disorders.
AB  - Drawing on a normative sample of 224 youth and their biological mothers, this
      study tested 4 family variables as potential mediators of the relationship
      between maternal depressive symptoms in early childhood and child psychological
      outcomes in preadolescence. The mediators examined included mother-child
      communication, the quality of the mother-child relationship, maternal social
      support, and stressful life events in the family. The most parsimonious
      structural equation model suggested that having a more problematic mother-child
      relationship mediated disruptive behavior-disordered outcomes for youths, whereas
      less maternal social support mediated the development of internalizing disorders.
      Gender and race were tested as moderators, but significant model differences did
      not emerge between boys and girls or between African American and Caucasian
      youths.

PMID- 14640805
TI  - Depressive symptoms and marital satisfaction: within-subject associations and the
      moderating effects of gender and neuroticism.
AB  - Given the emphasis on within-subject associations between depression and marital
      quality in recent theory and practice, this study was undertaken with three
      goals: to examine within-subject associations between depressive symptoms and
      marital quality over time, to address gender differences in the magnitude and
      direction of these associations, and to determine whether neuroticism moderates
      the strength of these associations. A total of 164 newly wed couples provided 8
      waves of data over 4 years of marriage. Hierarchical linear modeling confirmed
      the existence of bidirectional within-subject associations between marital
      satisfaction and depressive symptoms. Gender differences were rarely significant.
      Although neuroticism strengthened the effect of marital distress on symptoms as
      predicted, it weakened the effect of symptoms on marital distress among husbands.
      The theoretical and practical implications of these findings are discussed.

PMID- 14640806
TI  - Parenting behaviors and the occurrence and co-occurrence of depressive symptoms
      and conduct problems among african american children.
AB  - The occurrence and co-occurrence of depressive symptoms and conduct problems were
      examined in the context of parenting behaviors in a community-based sample of 897
      African American children and their primary caregivers using a multi-informant,
      longitudinal design. Parenting behaviors and clinical symptoms were assessed in 2
      waves, when the children averaged 10.5 and 12.3 years of age. Parenting behaviors
      differed significantly according to a child's symptomatology; (a) that is, when a
      child exhibited no depressive or conduct problems, (b) depressive problems only,
      (c) conduct problems only, or (d) co-occurring depressive and conduct problems.
      When parenting behaviors were examined according to changes in children's symptom
      levels, children whose symptoms increased over time reported increases in
      hostility and harsh-inconsistent parenting and decreases in warmth and nurturant
      involved parenting.

PMID- 14640807
TI  - Children's physiological indices of empathy and their socioemotional adjustment:
      does caregivers' expressivity matter?
AB  - Relations of heart rate and skin conductance reactions to mildly evocative
      empathy-inducing slides with socioemotional functioning were examined for 154
      children (mean age = 9 years, 5 months). In addition, maternal expressivity was
      tested as a moderator of these relations. Parents and teachers rated children's
      socioemotional functioning, and a behavioral measure of children's regulation was
      obtained. Boys who exhibited higher skin conductance and higher heart rate to
      slides depicting negative emotions were better regulated, less emotionally
      intense, and better adjusted than their peers. Furthermore, boys' regulation and
      adjustment were positively related to such physiological responding to negative
      slides if maternal negative expressivity was relatively low or moderate, but not
      high. Fewer findings were obtained for girls or for positive slides.

PMID- 14640808
TI  - Harsh parenting in relation to child emotion regulation and aggression.
AB  - This study presents a model of harsh parenting that has an indirect effect, as
      well as a direct effect, on child aggression in the school environment through
      the mediating process of child emotion regulation. Tested on a sample of 325
      Chinese children and their parents, the model showed adequate goodness of fit.
      Also investigated were interaction effects between parents' and children's
      gender. Mothers' harsh parenting affected child emotion regulation more strongly
      than fathers', whereas harsh parenting emanating from fathers had a stronger
      effect on child aggression. Fathers' harsh parenting also affected sons more than
      daughters, whereas there was no gender differential effect with mothers' harsh
      parenting. These results are discussed with an emphasis on negative emotionality
      as a potentially common cause of family perturbations, including parenting and
      child adjustment problems.

PMID- 14640809
TI  - Positive and negative emotional feelings and behaviors in mother-daughter ties in
      late life.
AB  - Behaviors and emotions during specific visits may reveal the interpersonal
      processes of mother-daughter ties, yet most research uses global assessments of
      these ties. Forty-eight mother-daughter pairs participated in audiotaped
      conversations and completed surveys. All mothers were over age 70 and in good
      health. Daughters tended to take a central role in structuring the conversations.
      Conversations were characterized by high levels of felt and expressed positive
      emotions and behaviors for mothers and daughters. Nevertheless, mothers reported
      more positive and fewer negative emotions, whereas daughters expressed more
      positive behaviors than did mothers. Mothers' positive feelings and behaviors
      were associated with daughters'. Finally, mothers' and daughters' emotions and
      behaviors were associated with their destructive responses to being upset with
      each other, providing support for the ambivalence perspective of parent-offspring
      relationships.

PMID- 14640810
TI  - Impact of elaboration on socially desirable responding and the validity of
      biodata measures.
AB  - The current study investigated the impact of requiring respondents to elaborate
      on their answers to a biodata measure on mean scores, the validity of the biodata
      item composites, subgroup mean differences, and correlations with social
      desirability. Results of this study indicate that elaborated responses result in
      scores that are much lower than nonelaborated responses to the same items by an
      independent sample. Despite the lower mean score on elaborated items, it does not
      appear that elaboration affects the size of the correlation between social
      desirability and responses to biodata items or that it affects criterion-related
      validity or subgroup mean differences in a practically significant way.

PMID- 14640812
TI  - Reduction of work-family conflict through the use of selection, optimization, and
      compensation behaviors.
AB  - Prior research has examined both the antecedents to and outcomes of work-family
      conflict. However, little is known about the existence and efficacy of behavioral
      strategies that may be used by individuals to reduce the amount of stressors
      experienced both on the job and at home, which result in work-family conflict.
      The purpose of this study was to examine the role of selection, optimization, and
      compensation (SOC) behaviors in relation to both job and family stressors and
      work-in-family (WIF) conflict and family-in-work (FIW) conflict. Results suggest
      that the use of general SOC behaviors in both the work and family domains are
      related to lower amounts of job and family stressors and subsequently lower
      amounts of WIF conflict and FIW conflict. In general, these results held true
      even when additional variables (e.g., hours worked, gender, job involvement,
      family involvement, social support, and supervisor support) were controlled.
      Implications of these results are discussed.

PMID- 14640811
TI  - Cohesion and performance in groups: a meta-analytic clarification of construct
      relations.
AB  - Previous meta-analytic examinations of group cohesion and performance have
      focused primarily on contextual factors. This study examined issues relevant to
      applied researchers by providing a more detailed analysis of the criterion
      domain. In addition, the authors reinvestigated the role of components of
      cohesion using more modern meta-analytic methods and in light of different types
      of performance criteria. The results of the authors' meta-analyses revealed
      stronger correlations between cohesion and performance when performance was
      defined as behavior (as opposed to outcome), when it was assessed with efficiency
      measures (as opposed to effectiveness measures), and as patterns of team workflow
      became more intensive. In addition, and in contrast to B. Mullen and C. Copper's
      (1994) meta-analysis, the 3 main components of cohesion were independently
      related to the various performance domains. Implications for organizations and
      future research on cohesion and performance are discussed.

PMID- 14640813
TI  - A lengthy look at the daily grind: time series analysis of events, mood, stress,
      and satisfaction.
AB  - The present study investigated processes by which job stress and satisfaction
      unfold over time by examining the relations between daily stressful events, mood,
      and these variables. Using a Web-based daily survey of stressor events, perceived
      strain, mood, and job satisfaction completed by 14 university workers, 1,060
      occasions of data were collected. Transfer function analysis, a multivariate
      version of time series analysis, was used to examine the data for relationships
      among the measured variables after factoring out the contaminating influences of
      serial dependency. Results revealed a contrast effect in which a stressful event
      associated positively with higher strain on the same day and associated
      negatively with strain on the following day. Perceived strain increased over the
      course of a semester for a majority of participants, suggesting that effects of
      stress build over time. Finally, the data were consistent with the notion that
      job satisfaction is a distal outcome that is mediated by perceived strain.

PMID- 14640814
TI  - It's different to give than to receive: predictors of givers' and receivers'
      reactions to favor exchange.
AB  - The present research examines episodes of favor exchange among peer employees. We
      posit that favor receivers' and favor givers' commitment to their exchange
      relationships with one another will be accounted for by different factors. As
      predicted, in 2 different organizational contexts, receivers' commitment to their
      relationships with givers was found to be more related to their judgments of the
      givers' interactional justice when performing the favor, whereas givers'
      commitment to their relationships with receivers was shown to be more associated
      with their judgments of the favorability of the outcomes associated with the
      favor that they performed. The implications of these findings for how givers and
      receivers can better manage favor exchange, and hence their relationships with
      each other, are discussed.

PMID- 14640815
TI  - Differential prediction and the use of multiple predictors: the omitted variables
      problem.
AB  - Moderated regression is widely used to examine differential prediction by race or
      gender. When using multiple predictors in a selection system, guidance as to
      whether differential prediction analysis should be conducted on each predictor
      individually, or on the set of predictors in combination, is lacking. Analyzing
      predictors individually creates the possibility of an omitted variable problem.
      Army Project A data were used to examine differential prediction by race with the
      use of personality measures for 79 predictor-criterion combinations. Traditional
      analysis indicated predictive bias by intercept in 45 instances and by slope in 7
      instances; the inclusion of an Armed Services Vocational Aptitude Battery general
      factor as an additional predictor changed the conclusion in 32 cases for the
      intercept and in 3 cases for the slope.

PMID- 14640816
TI  - The role of acceptance and job control in mental health, job satisfaction, and
      work performance.
AB  - Acceptance, the willingness to experience thoughts, feelings, and physiological
      sensations without having to control them or let them determine one's actions, is
      a major individual determinant of mental health and behavioral effectiveness in a
      more recent theory of psychopathology. This 2-wave panel study examined the
      ability of acceptance also to explain mental health, job satisfaction, and
      performance in the work domain. The authors hypothesized that acceptance would
      predict these 3 outcomes 1 year later in a sample of customer service center
      workers in the United Kingdom (N = 412). Results indicated that acceptance
      predicted mental health and an objective measure of performance over and above
      job control, negative affectivity, and locus of control. These beneficial effects
      of having more job control were enhanced when people had higher levels of
      acceptance. The authors discuss the theoretical and practical relevance of this
      individual characteristic to occupational health and performance.

PMID- 14640817
TI  - A meta-analytic study of general mental ability validity for different
      occupations in the European community.
AB  - A comprehensive meta-analysis of the validity of general mental ability (GMA)
      measures across 12 occupational categories in the European Community (EC) is
      presented. GMA measures showed that there is validity generalization and large
      operational validities for job performance and training success in 11
      occupational groups. Results also showed that job complexity moderated the
      magnitude of the operational validity of GMA tests across three levels of job
      complexity: low, medium, and high. In general, results were similar to those
      found in the United States, although the European findings showed a slightly
      larger magnitude of operational validity in some cases. Theoretical and practical
      implications of these findings for personnel selection are discussed. ((c) 2003
      APA, all rights reserved)

PMID- 14640818
TI  - Effects of energy availability on immediate and delayed emotional reactions to
      work events.
AB  - This study focuses on daily work events as proximal stimuli for discrete
      emotional reactions and suggests that availability of energy resources required
      for coping with goal-disruptive events, or for capitalizing on new opportunities
      offered by goal-enhancing events, influences intensity of emotional reactions.
      Using experience-sampling methodology with a sample of hospital residents, it is
      shown that negative emotion and fatigue following disruptive events are
      intensified when only limited energy resources are available due to current
      workload. However, positive emotions, promoted by goal-enhancing events, are
      mitigated due to inability to capitalize on new opportunities or challenges.
      Aftereffects of work events reveal that the energizing effect of goal-enhancing
      events mitigates end-of-day fatigue and negative emotion on high-workload days,
      although the effect of disruptive events is diminished by the end of such days,
      apparently because of lesser conspicuity against a background of high workload.
      Theoretical and practical implications are discussed.

PMID- 14640819
TI  - Practice variability and transfer of training: the role of self-efficacy
      generality.
AB  - Practice variability has been shown to enhance transfer of training. The purpose
      of the present study was to examine the role of self-efficacy generality as a
      motivational mechanism in explaining the relationship between practice
      variability and transfer. Undergraduate students (N = 82) were randomly assigned
      to 1 of 2 training conditions (constant or variable) for a computer decision
      making task. Measures of self-efficacy (intensity and generality) and transfer
      (near and far) were assessed. The results provided support for some of the
      hypothesized relationships. Specifically, practice variability led to increased
      self-efficacy generality. Both self-efficacy intensity and generality influenced
      far transfer performance, although only self-efficacy generality served as a
      mediator between practice variability and far transfer.

PMID- 14640820
TI  - Profiling active and passive nonrespondents to an organizational survey.
AB  - In this field study (N = 405) population profiling was introduced to examine
      general and specific classes of nonresponse (active vs. passive) to a
      satisfaction survey. The active nonrespondent group (i.e., purposeful
      nonresponders) was relatively small (approximately 15%). Active nonrespondents,
      in comparison with respondents, were less satisfied with the entity sponsoring
      the survey and were less conscientious. Passive nonrespondents (e.g., forgot),
      who represented the majority of nonrespondents, were attitudinally similar to
      respondents but differed with regard to personality. Nonresponse bias does not
      appear to be a substantive concern for satisfaction type variables--the typical
      core of an organizational survey. If the survey concerns topics strongly related
      to Conscientiousness and Agreeableness, the respondent sample may not be
      representative of the population.

PMID- 14640822
TI  - A daily process examination of the stress-response dampening effects of alcohol
      consumption.
AB  - The authors used a daily process design to assess alcohol's stress-response
      dampening (SRD) effects. Moderate to heavy social drinkers (N=100) reported on
      palmtop computers their alcohol consumption and social context in vivo for 30
      days. Participants also reported on their mood states in the late morning and
      early evening and completed a paper-and-pencil daily diary in which they recorded
      their negative events. The association between negative events and mood was
      weaker on days when individuals consumed alcohol prior to the final mood
      assessment. However, the moderating effect of alcohol on the negative event-mood
      association was limited to drinking in social situations. Alcohol's SRD effects
      varied as a function of several between-person risk factors.

PMID- 14640821
TI  - Smoking among psychiatric outpatients: relationship to substance use, diagnosis,
      and illness severity.
AB  - To understand the elevated smoking rates among psychiatric patients, the authors
      investigated whether psychiatric diagnosis, illness severity, and other substance
      use predicted smoking status in a diverse sample (N=2774) of psychiatric
      outpatients. Results indicated that 61% smoked daily and that 18% smoked heavily.
      Smoking was related to psychiatric diagnosis and illness severity as well as
      caffeine consumption and substance abuse. Diagnoses of bipolar disorder,
      schizoaffective disorder, and schizophrenia were independently related to smoking
      status, an association that was most pronounced among persons treated at clinics
      serving more impaired patients. Thus, diagnosis and illness severity contribute
      to elevated smoking rates, even after controlling for other substance use.
      Cessation programs are needed to reduce tobacco use in this vulnerable
      population.

PMID- 14640823
TI  - Social anxiety, negative affectivity, and substance use among high school
      students.
AB  - The literature regarding the relationship between adolescent social anxiety and
      substance use is sparse, and available studies have produced discrepant results.
      Similarly, negative affectivity is a mood-dispositional dimension that is
      infrequently considered in studies of substance use. The authors used
      dispositional structural equation modeling to examine the concurrent
      relationships of social anxiety and negative affectivity with adolescent
      substance involvement among 724 students in 1 southern California high school.
      The final model indicated that increased substance use was associated with having
      lower grade-point average, being male, being White, having higher levels of
      negative affectivity, and having lower levels of social anxiety. The findings
      confirm that negative affectivity is positively related to adolescent substance
      use, whereas social anxiety appears to be protective against substance
      involvement.

PMID- 14640824
TI  - Treatment of pathological gambling: a critical review of the literature.
AB  - The legalization and availability of new forms of gambling are increasing in most
      Western countries. This trend has contributed to the fact that more individuals
      are developing gambling problems. As a result, there is a need for effective
      treatments. Although gambling treatment dates several decades, few empirically
      supported treatments for pathological gambling have been developed. This critical
      review includes only controlled treatment studies. The primary inclusion
      criterion was randomization of participants to an experimental group and to at
      least 1 control group. Eleven studies were identified and evaluated. Key findings
      showed that cognitive-behavioral studies received the best empirical support.
      Recommendations to improve gambling treatment research include better validated
      psychometric measures, inclusion of process measures, better definition of
      outcomes, and more precise definition of treatments.

PMID- 14640825
TI  - Childhood ADHD and adolescent substance use: an examination of deviant peer group
      affiliation as a risk factor.
AB  - Deviant peer group affiliation was evaluated as a risk factor for substance use
      in adolescents with childhood attention-deficit/hyperactivity disorder (ADHD).
      Results showed that deviant peer affiliation mediated the relationship between
      ADHD and substance use, suggesting that children with ADHD are more likely than
      children without ADHD to become involved with deviant peers and, as a result,
      more likely to use substances. Moreover, the relationship between deviant peer
      affiliation and substance use was stronger for adolescents with ADHD, suggesting
      that once they are immersed in a deviant peer group, adolescents with ADHD are
      more vulnerable to the negative social influences of that group. This study is
      the first step in identifying high-risk pathways from childhood ADHD to substance
      use in adolescence.

PMID- 14640826
TI  - A daily diary validity test of drinking to cope measures.
AB  - Data from 2 daily diary studies of stress, negative affect, and drinking were
      used to examine the correspondence between global self-reports of drinking to
      cope (DTC) and within-person stress/negative affect-drinking associations. In
      Study 1, 83 community-residing drinkers recorded data in nightly booklets on
      negative events, perceived stress, negative affect, and drinking for 60
      consecutive days. In Study 2, 88 community-residing drinkers recorded data on
      negative events and negative interpersonal exchanges nightly and negative affect
      and drinking in near-real time on palmtop computers for 30 consecutive days. Both
      studies showed only modest correspondence between self-reported DTC and between
      person differences in within-day, daily, and weekly associations between
      stress/negative affect and drinking. The findings indicate that individuals who
      report higher DTC simply may drink across a wider variety of conditions than
      those who report relatively lower DTC.

PMID- 14640827
TI  - Family communication and religiosity related to substance use and sexual behavior
      in early adolescence: a test for pathways through self-control and prototype
      perceptions.
AB  - This research tested predictions about pathways to substance use and sexual
      behavior with a community sample of 297 African American adolescents (M age: 13.0
      years). Structural modeling indicated that parent-adolescent communication had a
      path to unfavorable prototypes of substance users; quality of parent-adolescent
      relationship had paths to good self-control, higher resistance efficacy, and
      unfavorable prototypes of sexually active teens; and religiosity had inverse
      direct effects to both substance use and sexual behavior. Self-control constructs
      had paths to prototypes of abstainers, whereas risk taking had paths to
      prototypes of drug and sex engagers and direct effects to outcomes. Prototypes
      had paths to outcomes primarily through resistance efficacy and peer
      affiliations. Effects were also found for gender, parental education, and
      temperament characteristics. Implications for self-control theory and prevention
      research are discussed.

PMID- 14640828
TI  - Can advertising increase awareness of problem gambling? A statewide survey of
      impact.
AB  - With the rapid rise of state-sponsored gambling during the 1990s, the number of
      problem gamblers increased as well. In this study, 800 Indiana adult residents
      were randomly surveyed to evaluate the impact of a statewide advertising campaign
      designed to increase awareness of problem gambling. The pre- to postcampaign
      telephone survey (with 400 independent respondents at each time point) targeted
      (a). the impact of the advertising campaign and (b). general awareness of problem
      gambling issues. Results indicated, overall, little impact of the ad campaign and
      a low rate of exposure to it (8%). Billboards and slogans appeared to be the
      methods with strongest impact. The sample had a positive view of problem gambling
      awareness campaigns and appeared quite knowledgeable about problem gambling in
      general. Awareness of state resources to aid problem gamblers was lower. Results
      are discussed in relation to the study methodology, and suggestions to improve
      future advertising efforts are offered.

PMID- 14640829
TI  - Assessing consequences of substance use: psychometric properties of the inventory
      of drug use consequences.
AB  - Negative consequences are an important component of the substance use change
      process, yet no standardized measure exists to assess consequences of use. This
      study evaluated the psychometric properties of the Inventory of Drug Use
      Consequences, a self-report measure assessing drinking and drug use consequences.
      Participants (N=252) were assessed at entry into outpatient substance abuse
      treatment. Items loaded strongly on 1 factor, and internal consistency of the
      total scale was high. Fifteen items with the highest correlations with the total
      scale were chosen to represent the construct. The shortened measure exhibited
      good internal consistency, convergent and discriminant validity, and detected
      change over time and may be the measure of substance use consequences that is
      lacking in the field.

PMID- 14640830
TI  - Is there a link between adolescent cigarette smoking and pharmacotherapy for
      ADHD?
AB  - There is continuing concern that pharmacotherapy for attention
      deficit/hyperactivity disorder (ADHD) may raise the risk of smoking (the gateway
      hypothesis). Alternatively, unmedicated people with ADHD may use nicotine to
      improve attentional and self-regulatory competence (the self-medication
      hypothesis). From a community sample of 511 adolescents participating in a
      longitudinal health study, 27 were identified as having ADHD, and 11 of these
      were receiving pharmacotherapy. Self-report surveys, electronic diaries, and
      salivary cotinine all indicated that adolescents treated with pharmacotherapy for
      ADHD smoked less than their untreated counterparts over 2 years of high school.
      These convergent findings from 3 disparate indicators lend support to the self
      medication hypothesis over the gateway hypothesis, although alternative
      explanations need further study. The findings also suggest that early treatment
      of psychological and behavioral problems may prevent or delay smoking initiation.

PMID- 14640831
TI  - Effect of cue exposure, urge to smoke, and nicotine deprivation on cognitive
      performance in smokers.
AB  - The primary aim of this investigation was to test the hypothesis that the urge to
      smoke interferes directly with cognitive performance. Fifty-four smokers were
      randomly assigned to 1 of 3 groups: (a). ad lib, (b). deprived, or (c). nicotine
      patch. Participants rated their urge to smoke on continuous visual analogue
      scales. Cognitive performance was determined by measuring reaction times (RTs) on
      a Sternberg task. The deprived group reported a higher urge and had longer RTs
      than the ad lib group when exposed to smoking-related cues. However, the nicotine
      patch group reported a higher urge in the absence of longer RTs. The results
      indicated that nicotine deprivation affects cognitive performance and that the
      urge to smoke only partially mediated RTs.

PMID- 14640832
TI  - Time-to-contact estimation of accelerated stimuli is based on first-order
      information.
AB  - The goal of this study was to test whether 1st-order information, which does not
      account for acceleration, is used (a) to estimate the time to contact (TTC) of an
      accelerated stimulus after the occlusion of a final part of its trajectory and
      (b) to indirectly intercept an accelerated stimulus with a thrown projectile.
      Both tasks require the production of an action on the basis of predictive
      information acquired before the arrival of the stimulus at the target and allow
      the experimenter to make quantitative predictions about the participants' use (or
      nonuse) of 1st-order information. The results show that participants do not use
      information about acceleration and that they commit errors that rely
      quantitatively on 1st-order information even when acceleration is
      psychophysically detectable. In the indirect interceptive task, action is planned
      about 200 ms before the initiation of the movement, at which time the 1st-order
      TTC attains a critical value.

PMID- 14640833
TI  - Modeling effects of rhythmic context on perceived duration: a comparison of
      interval and entrainment approaches to short-interval timing.
AB  - Relative merits of interval and entrainment conceptions of the internal clock
      were assessed within a common theoretical framework by 4 time-judgment
      experiments. The timing of tone onsets marking the beginning and ending of
      standard and comparison time intervals relative to a context rhythm were
      manipulated: onsets were on time, early, or late relative to the implied rhythm,
      and 2 distinct accuracy patterns emerged. A quadratic ending profile indicated
      best performance when the standard ended on time and worst performance when it
      was early or late, whereas a flat beginning profile (Experiments 1-3) indicated
      uniform performance for the 3 expectancy conditions. Only in Experiment 4, in
      which deviations from expected onset times were large, did significant effects of
      beginning times appear in time-discrimination thresholds and points of subjective
      equality. Findings are discussed in the context of theoretical assumptions about
      clock resetting, the representation of time, and independence of successive time
      intervals.

PMID- 14640834
TI  - The locus of redundant-targets and nontargets effects: evidence from the
      psychological refractory period paradigm.
AB  - In target detection tasks, responses are faster when displays have 2 targets
      (redundant-targets effect; RTE) and slower when they have no targets (nontargets
      effect; NTE) relative to displays with a single target. The psychological
      refractory period paradigm was used to localize these effects. In Experiment 1,
      participants classified tones as high or low and then classified letters as
      targets or nontargets after a short or long stimulus onset asynchrony (SOA). The
      magnitudes of the RTE and NTE did not depend on SOA. In Experiment 2, the order
      of the tasks was reversed, and at short SOAs the RTE and NTE had similar
      magnitudes for both tone discrimination and target detection responses. These
      findings suggest that the RTE and NTE arise during response selection.
      Interactive effects of tone pitch with the number and type of target features
      were also observed, and these were tentatively interpreted as synesthetic
      effects.

PMID- 14640835
TI  - Infants' long-term memory for the sound patterns of words and voices.
AB  - Infants' long-term memory for the phonological patterns of words versus the
      indexical properties of talkers' voices was examined in 3 experiments using the
      Headturn Preference Procedure (D. G. Kemler Nelson et al., 1995). Infants were
      familiarized with repetitions of 2 words and tested on the next day for their
      orientation times to 4 passages--2 of which included the familiarized words. At
      7.5 months of age, infants oriented longer to passages containing familiarized
      words when these were produced by the original talker. At 7.5 and 10.5 months of
      age, infants did not recognize words in passages produced by a novel female
      talker. In contrast, 7.5-month-olds demonstrated word recognition in both talker
      conditions when presented with passages produced by both the original and the
      novel talker. The findings suggest that talker-specific information can prime
      infants' memory for words and facilitate word recognition across talkers.

PMID- 14640836
TI  - Recognition of interlingual homophones in bilingual auditory word recognition.
AB  - How do bilinguals recognize interlingual homophones? In a gating study, word
      identification and language membership decisions by Dutch-English bilinguals were
      delayed for interlingual homophones relative to monolingual controls. At the same
      time, participant judgments were sensitive to subphonemic cues. These findings
      suggest that auditory lexical access is language nonselective but is sensitive to
      language-specific characteristics of the input. In 2 cross-modal priming
      experiments, visual lexical decision times were shortest for monolingual controls
      preceded by their auditory equivalents. Response times to interlingual homophones
      accompanied by their corresponding auditory English or Dutch counterparts were
      also shorter than in unrelated conditions. However, they were longer than in the
      related monolingual control conditions, providing evidence for online competition
      of the 2 near-homophonic representations. Experiment 3 suggested that
      participants used sublexical cues to differentiate the 2 versions of a homophone
      after language nonselective access.

PMID- 14640837
TI  - Proprioceptive perception of phase variability.
AB  - Previous work has established that judgments of relative phase variability of 2
      visually presented oscillators covary with mean relative phase. Ninety degrees is
      judged to be more variable than 0 degrees or 180 degrees, independently of the
      actual level of phase variability. Judged levels of variability also increase at
      180 degrees. This pattern of judgments matches the pattern of movement
      coordination results. Here, participants judged the phase variability of their
      own finger movements, which they generated by actively tracking a manipulandum
      moving at 0 degrees, 90 degrees, or 180 degrees, and with 1 of 4 levels of Phase
      Variability. Judgments covaried as an inverted U-shaped function of mean relative
      phase. With an increase in frequency, 180 degrees was judged more variable
      whereas 0 degrees was not. Higher frequency also reduced discrimination of the
      levels of Phase Variability. This matching of the proprioceptive and visual
      results, and of both to movement results, supports the hypothesized role of
      online perception in the coupling of limb movements. Differences in the 2 cases
      are discussed as due primarily to the different sensitivities of the systems to
      the information.

PMID- 14640838
TI  - Direct assessments of the processing time hypothesis for the missing-letter
      effect.
AB  - When participants search for a target letter while reading, they make more
      omissions if the target letter is embedded in frequently used words or in the
      most frequent meaning of a polysemic word. According to the processing time
      hypothesis, this occurs because familiar words and meanings are identified
      faster, leaving less time for letter identification. Contrary to the predictions
      of the processing time hypothesis, with a rapid serial visual presentation
      procedure, participants were slower at detecting target letters for more frequent
      words or the most frequent meaning of a word (Experiments 1 and 2) or at
      detecting the word itself instead of a target letter (Experiment 3). In
      Experiments 4 and 5, participants self-initiated the presentation of each word,
      and the same pattern of results was observed as in Experiments 1 and 3. Positive
      correlations were also found between omission rate and response latencies.

PMID- 14640839
TI  - Temporal variations in visual completion: a reflection of spatial limits?
AB  - The completion of partly occluded objects appears instantaneous and effortless,
      but empirically takes measurable time. The current study investigates how amount
      of occlusion affects the time course and mechanisms of visual completion.
      Experiment 1 used a primed-matching paradigm to determine completion times for
      objects occluded by various amounts. Experiments 2 and 3 used a dot-localization
      paradigm to probe completed contour representations for a qualitative shift above
      some spatial limit. The results demonstrate that time to completion rises with
      amount of occlusion. Nonetheless, the visual system can complete highly occluded
      objects, even when the occlusion renders visible contours nonrelatable.
      Furthermore, prolonged completion times for highly occluded objects do not result
      from a breakdown of low-level interpolation processes: The same contour
      completion mechanism operates on objects occluded by different spatial extents.

PMID- 14640840
TI  - Does facial expression affect attention orienting by gaze direction cues?
AB  - In 6 experiments, the authors investigated whether attention orienting by gaze
      direction is modulated by the emotional expression (neutral, happy, angry, or
      fearful) on the face. The results showed a clear spatial cuing effect by gaze
      direction but no effect by facial expression. In addition, it was shown that the
      cuing effect was stronger with schematic faces than with real faces, that gaze
      cuing could be achieved at very short stimulus onset asynchronies (14 ms), and
      that there was no evidence for a difference in the strength of cuing triggered by
      static gaze cues and by cues involving apparent motion of the pupils. In sum, the
      results suggest that in normal, healthy adults, eye direction processing for
      attention shifts is independent of facial expression analysis.

PMID- 14640841
TI  - A linear optical trajectory informs the fielder where to run to the side to catch
      fly balls.
AB  - P. McLeod, N. Reed, and Z. Dienes (2002) argued that the linear optical
      trajectory (LOT) strategy incorrectly cues fielders to run forward for balls
      headed beyond them. The authors of this article explain that the downward optical
      curvature found for balls landing beyond the fielder's initial position occurs
      because the balls reorient the direction the fielder is facing during pursuit.
      Thus, when downward optical curvature begins, the ball is headed to land in front
      of where the fielder is facing and running. This investigation of open-loop
      failure conditions has led to new insights such as the reorientation of the
      fielder, and it supports the use of maintaining matching rates of vertical and
      lateral optical ball movement consistent with primacy of the LOT control
      mechanism even when interception is unachievable.

PMID- 14640842
TI  - Signal detection theory analyses of semantic priming in word recognition.
AB  - Word recognition, semantic priming, and cognitive impenetrability research have
      used signal detection theory (SDT) measures to separate perceptual and
      postperceptual processes. In the D. Norris (1986) checking model and model
      simulation (D. Norris, 1995), priming alters only postperceptual word decision
      criteria: Stimulus-related priming reduces uncertainty, increasing sensitivity;
      stimulus-unrelated priming increases false alarms more than hits, reducing
      sensitivity. This work is cited as strong evidence that criterion changes can
      alter perceptual sensitivity and that SDT is inappropriate for investigating
      complex cognitive processes. The authors' current SDT ideal observer analysis of
      the model demonstrates that related priming does not directly alter sensitivity
      and that unrelated priming increases only false-alarm rate, reducing sensitivity.
      This analysis provides new perspectives on SDT concepts of complex decision
      processing.

PMID- 14640843
TI  - Still no evidence for perfect timesharing with two ideomotor-compatible tasks: a
      reply to Greenwald (2003).
AB  - For 30 years, A. G. Greenwald and H. G. Shulman's (1973) psychological refractory
      period (PRP) study has been cited as evidence for perfect timesharing with
      ideomotor (IM)-compatible tasks. Recently, M.-C. Lien, R. W. Proctor, and P. A.
      Allen (2002) failed to replicate these results and concluded that IM
      compatibility is neither necessary nor sufficient to eliminate the PRP effect. A.
      G. Greenwald (2003) attributed Lien et al.'s nonreplication to the use of (a) a
      non-IM-compatible task, (b) varied trial spacing, and/or (c) inappropriate
      instructions. The authors of the present article argue that the first 2 factors
      are not critical and that instructions merely affect the criterion for speed
      versus accuracy. In each of Greenwald's experiments, dual-task costs were evident
      on response time or error rates. Furthermore, the small dual-task costs in his
      study are consistent with a bottleneck model. Thus, Greenwald (2003) does not
      provide evidence that IM-compatible tasks enable perfect timesharing.

PMID- 14640844
TI  - The effect of category learning on the representation of shape: dimensions can be
      biased but not differentiated.
AB  - Recent studies have suggested a profound influence of category learning on visual
      perception, resulting in independent processing of previously integral
      dimensions. The authors reinvestigate this issue for shape dimensions. They first
      extend previous findings that some shape dimensions (aspect ratio and curvature)
      are processed in a separable way, whereas others (radial frequency components)
      are not. They then show that a category-learning phase improved the
      discrimination of a relevant with respect to an irrelevant dimension, but only
      for separable dimensions. No similar effect was found on the relative sensitivity
      for integral shape dimensions. Thus, category learning is capable of biasing
      separable shape dimensions but does not alter the status of dimensions in the
      visual system as either separable or integral.

PMID- 14640845
TI  - Dissociations of personally significant and task-relevant distractors inside and
      outside the focus of attention: a combined behavioral and psychophysiological
      study.
AB  - Studies of attentional capture by personally significant stimuli have reached
      inconsistent results, possibly because of improper control of the participants'
      attention. In the present study, the authors controlled visual attention by using
      a Stroop-like task. Participants responded to a central color and ignored a word
      presented either centrally (i.e., at the focus of attention) or peripherally
      (i.e., outside the focus of attention). Central words led to slower reaction
      times and larger orienting responses for significant items than for neutral
      items. These effects largely disappeared when the words appeared in a peripheral
      location. The peripheral words interfered with performance when they were
      relevant to task demands. These results indicate that there is a fundamental
      difference between task-relevant words and personally significant words: The
      former capture attention even when presented peripherally, whereas the latter do
      not.

PMID- 14640846
TI  - The dynamics of learning and allocation of study time to a region of proximal
      learning.
AB  - In contrast to the dominant discrepancy reduction model, which favors the most
      difficult items, people, given free choice, devoted most time to medium
      difficulty items and studied the easiest items first. When study time was
      experimentally manipulated, best performance resulted when most time was given to
      the medium-difficulty items. Empirically determined information uptake functions
      revealed steep initial learning for easy items with little subsequent increase.
      For medium-difficulty items, initial gains were smaller but more sustained,
      suggesting that the strategy people had used, when given free choice, was largely
      appropriate. On the basis of the information uptake functions, a negative spacing
      effect was predicted and observed in the final experiment. Overall, the results
      favored the region of proximal learning framework.

PMID- 14640847
TI  - Routine and the perception of time.
AB  - The authors investigated the influence of routine on people's estimation of time,
      testing the hypothesis that duration is remembered as being shorter when time is
      spent in a routine activity. In 4 experiments and 2 field studies, the authors
      compared time estimations in routine and nonroutine conditions. Routine was
      established by a sequence of markers (Study 1), variation of the task (Studies 2
      and 3), or the number of repetitive blocks (Study 4). As hypothesized, the
      duration of the task was remembered as being shorter in routine conditions than
      in nonroutine ones. This trend was reversed in experienced (prospective)
      judgments when participants were informed beforehand of the duration-judgment
      task (Study 3). In Studies 5 and 6, the authors examined remembered duration
      judgments of vacationers and kibbutz members, which provided further support for
      the main hypothesis.

PMID- 14640848
TI  - Recollection, fluency, and the explicit/implicit distinction in artificial
      grammar learning.
AB  - In this article, the authors propose that both implicit memory and implicit
      learning phenomena can be explained by a common set of principles, in particular
      via participants' strategic use of recollective and fluency heuristics. In a
      series of experiments, it was demonstrated that manipulating processing fluency
      had an impact on classification decisions in an artificial grammar learning task
      (Experiments 1, 2, 4, and 7), showing that participants were using a fluency
      heuristic. Under identical conditions, however, this manipulation had no effect
      on recognition decisions (Experiments 3 and 5), consistent with a greater default
      reliance on recollection. Most significant, the authors also showed that a
      fluency effect can be induced in recognition (Experiments 4-6) and can be
      eliminated in classification (Experiment 7).

PMID- 14640849
TI  - Executive functioning as a potential mediator of age-related cognitive decline in
      normal adults.
AB  - Critical requirements for the hypothesis that executive functioning is a
      potential mediator of age-related effects on cognitive functioning are that
      variables assumed to reflect executive functioning represent a distinct construct
      and that age-related effects on other types of cognitive functioning are reduced
      when measures of executive functioning are statistically controlled. These issues
      were investigated in a study involving 261 adults between 18 and 84 years of age.
      Although age-related effects on various cognitive abilities were substantially
      reduced after statistical control of the variance in measures hypothesized to
      represent executive functioning, there was only weak evidence for the existence
      of distinct constructs corresponding to executive functioning or to aspects of
      executive control concerned with inhibition, updating, or time sharing.

PMID- 14640850
TI  - The effect of verbal context on olfactory perception.
AB  - Three experiments were conducted to examine how verbal context and sensory
      stimulation interact to influence odor hedonic perception. Eight common odors
      were presented in their natural and synthetic forms, and verbal labels
      designating name and source (natural, synthetic) information were either
      explicitly given, self-generated, falsely provided, or not provided. Results
      revealed that verbal information about source influenced hedonic ratings whether
      or not the odorant itself was also present. When odorants were presented without
      verbal labels, olfactory evaluations were based in sensation. Name and source
      information contributed different levels of meaning and influence to perceptual
      evaluations. The findings are discussed with reference to an experiential
      collocation model for odor-label interactions and a dual-coding hypothesis for
      olfactory perception.

PMID- 14640851
TI  - Introduction to the special section on health and cognitive function.
AB  - Numerous factors related to health and diseases have been studied in relation to
      cognitive function. It has been shown that across the life span, systemic medical
      diseases can negatively impact cognitive function. Factors that influence the
      development of medical diseases, such as poor health habits, biological risk
      factors, hormones, genetic factors, exposure to environmental toxins, and certain
      treatments for disease, can also have an adverse effect on cognitive function.
      Conversely, factors such as high levels of education, good health habits, and
      some treatments for disease can be protective. Included in this special section
      are 6 empirical articles that examine the relation of health or disease to
      cognitive function.

PMID- 14640852
TI  - Relation between cardiovascular and metabolic disease and cognition in very old
      age: cross-sectional and longitudinal findings from the berlin aging study.
AB  - This study documented findings on the relation between cognitive functioning
      (perceptual speed, memory, fluency, and knowledge) and cardiovascular and
      metabolic disease in a sample of very old adults (ages 70 and older), both cross
      sectionally (n=516) and longitudinally (n=206) in a 4-year follow-up. After age,
      SES, sex, and dementia status were controlled for, 4 diagnoses were negatively
      associated with cognition: congestive heart failure, stroke, coronary heart
      disease, and diabetes mellitus, with a joint effect of 0.47 standard deviations.
      The impact of disease status was largest on perceptual speed and fluency, memory
      was impacted only by diabetes, and knowledge was not related to any somatic
      diagnosis. There was no differential decline in participants diagnosed with 1 of
      these 4 diseases and those who were not. The only cardiovascular risk factor
      associated with cognitive performance was alcohol consumption.

PMID- 14640853
TI  - Acute neuropsychological changes in hemodialysis and peritoneal dialysis
      patients.
AB  - This study examined the impact of different dialysis treatments on the
      neuropsychological (NP) functioning of 145 end-stage renal disease patients.
      Hemodialysis (HD) and peritoneal dialysis (PD) patients were administered an NP
      test battery and measures of mood on 2 consecutive days (pre- and 24 hr
      postdialysis). Biochemistry was assessed at each session. Results indicated
      significant improvements in NP functioning (attention, concentration, verbal and
      visual memory, and psychomotor speed) in HD patients 24 hr postdialysis. No such
      fluctuations were found in PD patients. Although biochemical changes were found
      in the HD patients at the same time points, these were not consistently related
      to the NP changes.

PMID- 14640854
TI  - Cognitive change 5 years after coronary artery bypass surgery.
AB  - A longitudinal study of cognitive function after coronary artery bypass surgery
      examined 107 participants using 11 tests, preoperatively and at 6 days, 8 weeks,
      and 5 years after surgery. The overall neuropsychological (NP) change score
      declined at 6 days, showed some recovery at 8 weeks, and declined again at 5
      years. The number of microemboli recorded during surgery, postoperative short
      term cognitive change, and degree of recovery at 8 weeks were identified as
      predictors of change in NP score to 5 years. This suggests that even over a 5
      year period, operative damage is detectable. Patients' vulnerability to short
      term deterioration and resilience or ability to recover over a few weeks from
      operative cerebral insult are important processes of unknown mechanisms.

PMID- 14640855
TI  - Effects of hypertension on attention, memory, and executive function in older
      adults.
AB  - Hypertension is associated with impairments in cognitive function in older
      adults, but the nature and extent of these deficits are unclear. Brief cognitive
      measures lack sensitivity, whereas comprehensive assessments produce numerous
      variables that are difficult to interpret. The authors performed a principal
      components analysis using a computerized cognitive assessment battery and
      neuropsychological measures of executive function in 506 hypertensive and
      normotensive older participants. Composite factor scores were used to reanalyze
      data from 223 untreated participants without vascular complications. The
      hypertensive group had deficits in Speed of Cognition, Episodic and Working
      Memory, and Executive Function but not Continuity of Attention. Using composite
      scores simplified data interpretation and suggested differential effects of
      hypertension on cognitive performance not clearly evident in individual test
      results.

PMID- 14640856
TI  - Biological and psychological factors associated with memory function in
      fibromyalgia syndrome.
AB  - Fibromyalgia is a stress-related disorder characterized by chronic pain, memory
      impairment, and neuroendocrine aberrations. With the hypothesis that biological
      and psychological symptoms may underlie the cognitive problems, the relative
      influences of neuroendocrine function and psychological factors on declarative
      memory were examined among 50 women with fibromyalgia. This within-group analysis
      controlled for age, education, pain, and relevant medications. Neuroendocrine
      function and depression had significant independent associations with memory
      function. Higher log-transformed mean salivary cortisol levels were associated
      with better performance on both immediate and delayed visual recall and with
      delayed verbal recall. Depressive symptoms were negatively associated with verbal
      recall. These findings suggest that a basic disorder of endocrine stress
      responses may contribute to the cognitive symptoms experienced by fibromyalgia
      patients.

PMID- 14640857
TI  - Cognitive and psychological outcomes of exercise in a 1-year follow-up study of
      patients with chronic obstructive pulmonary disease.
AB  - This study evaluated outcomes of self-directed exercise activity on cognitive
      functioning and psychological well-being among 28 adults with chronic obstructive
      pulmonary disease (COPD). Participants had completed an intensive 10-week program
      of exercise training and were given an exercise prescription to follow. One year
      later, participants completed comprehensive assessments of physical, cognitive,
      and psychological functioning. At follow-up, 39% (n=11) had continued with a
      regular program of moderate intensity exercise. Repeated measures analysis of
      variance indicated that exercise adherent participants maintained gains they had
      achieved in the initial exercise intervention, but nonexercise participants
      experienced declines in functional capacity, cognitive performance, and
      psychological well-being. Continued exercise among patients with COPD is
      associated with maintenance of physical, cognitive, and psychological
      functioning.

PMID- 14640859
TI  - Changes in heavy drinking over the third decade of life as a function of
      collegiate fraternity and sorority involvement: a prospective, multilevel
      analysis.
AB  - Although affiliation with a fraternity or sorority is an important risk factor
      for heavy drinking, recent research indicates that this risk may be limited to
      the college years. Random coefficient growth modeling was used to track changes
      in patterns of heavy drinking over the course of 11 years as a function of gender
      and collegiate Greek involvement (N=318). Overall, greater cumulative exposure to
      the Greek system led to increased heavy drinking during the college years,
      particularly among men. Shortly after leaving college, heavy drinking levels
      dropped markedly and remained low through approximately age 30. Inclusion of peer
      alcohol use norms in the model reduced the influence of Greek involvement.
      Implications for models of heavy drinking and health risks are discussed.

PMID- 14640858
TI  - Stability of older adults' preferences for life-sustaining medical treatment.
AB  - The use of instructional advance directives assumes that preferences for life
      sustaining medical treatment remain stable over time and across changes in life
      condition. A sample of 332 older adults recorded their preferences for 4 life
      sustaining treatments in 9 illness scenarios. These preferences were elicited
      again 1 and 2 years after the original interview. Overall, preferences for life
      sustaining treatment were moderately stable over time, but stability varied
      significantly across judgments. Preferences were most stable for illness
      scenarios that were most and least serious and for decisions to refuse treatment.
      Age, gender, education, and prior completion of an advance directive were all
      related to preference stability, and evidence indicated that declines in physical
      or psychological functioning resulted in decreased interest in life-sustaining
      treatment.

PMID- 14640860
TI  - Coping style as a predictor of health and well-being across the first year of
      medical school.
AB  - Medical students in their 1st year (N=71) were assessed prior to starting
      training and at year's end. Coping styles reported at baseline were strongly
      related to coping styles at the end of the year. Students' physical health and
      psychological well-being declined over the course of the year. The greater the
      students' use of both problem-focused coping and approach emotion-focused coping,
      the less their physical health deteriorated. Psychological well-being at year's
      end was more strongly related to baseline functioning, and coping style did not
      predict change. This study demonstrated the utility of measuring coping style and
      the predictive ability of coping on physical health in a healthy sample.

PMID- 14640861
TI  - Racial and body image differences in coping for women diagnosed with breast
      cancer.
AB  - Although more White women develop breast cancer, African American women more
      frequently die of the disease (American Cancer Society, 2003). Despite higher
      morbidity among African American women, few studies have included racially
      diverse samples. The purposes of this study were to explore racial and body image
      differences in coping and self-efficacy in coping and racial differences in body
      image perceptions among breast cancer patients. The 92 participants ranged in age
      from 28 to 86 years (M=57.64, SD=12.48). Participants with higher body image
      perceptions had significantly higher self-efficacy in coping compared with
      participants with lower body image perceptions. There were no significant racial
      or ethnic differences in coping, self-efficacy in coping, or body image
      perceptions.

PMID- 14640862
TI  - Relationships between perceived stress and health behaviors in a sample of
      working adults.
AB  - The study examined associations between perceived stress and fat intake,
      exercise, alcohol consumption, and smoking behaviors. Data were from surveys of
      12,110 individuals in 26 worksites participating in the SUCCESS project (D. J.
      Hennrikus, R. W. Jeffery, & H. A. Lando, 1995), a study of smoking cessation
      interventions. Linear regression analyses examined cross-sectional associations
      between stress level and health behaviors. Analyses were stratified by gender and
      controlled for demographics. High stress for both men and women was associated
      with a higher fat diet, less frequent exercise, cigarette smoking, recent
      increases in smoking, less self-efficacy to quit smoking, and less self-efficacy
      to not smoke when stressed. Stress was not associated with alcohol intake.
      Findings suggest that the association between stress and disease may be moderated
      in part by unhealthy behaviors.

PMID- 14640863
TI  - Correlates of functional disability in patients with postural tachycardia
      syndrome: preliminary cross-sectional findings.
AB  - The study investigated correlates of functional disability in 94 patients (89.4%
      women, 10.6% men; mean age=34.2 years) with postural tachycardia syndrome (POTS),
      a clinical syndrome of orthostatic intolerance characterized by significant
      functional limitations. Path analysis supported a model in which, controlling for
      demographic and disease variables, catastrophic cognitions were directly related
      to the latent variable functional disability, whereas somatic vigilance, anxiety
      sensitivity, and neuroticism were indirectly associated with functional
      disability through their relationship with catastrophic cognitions. Results
      suggest that modifiable psychological factors play a role in the functional
      limitations experienced by patients with POTS. Longitudinal research is necessary
      to confirm these relationships.

PMID- 14640864
TI  - Psychosocial variables, external barriers, and stage of mammography adoption.
AB  - Guided by H. Triandis's (1980) theory of behavior and the transtheoretical model,
      the study purpose was to examine differences in psychosocial variables and
      external conditions by stage of mammography adoption. Sampled from a statewide
      population, participants (N=509) were women aged 51-80. They had been contacted
      by telephone, screened for eligibility (e.g., no history of cancer or recent
      mammogram), and interviewed 3-6 months later. Higher utility beliefs, social
      influences, and practitioner interactions about mammography were associated with
      improved stage of adoption, as were lower negative affect and external barriers
      regarding mammography. Higher decisional balance scores, with and without
      negative affect toward mammography were associated with improved stage.
      Controlling for variables reflecting pros and cons, negative affect toward
      mammography further distinguished among stages. A richer set of pros and cons
      measures could explain screening more fully.

PMID- 14640866
TI  - Determinants of balance confidence in community-dwelling elderly people.
AB  - BACKGROUND AND PURPOSE: The fear of falling can have detrimental effects on
      physical function in the elderly population, but the relationship between a
      persons' confidence in the ability to maintain balance and actual balance ability
      and functional mobility is not known. The extent to which balance confidence can
      be explained by balance performance, functional mobility, and sociodemographic,
      psychosocial, and health-related factors was the focus of this study. SUBJECTS:
      The subjects were 50 community-dwelling elderly people, aged 65 to 95 years
      (mean=81.7, SD=6.7). METHODS: Balance was measured using the Berg Balance Scale.
      Functional mobility was measured using the Timed Up Go Test. The Activities
      specific Balance Scale was used to assess balance confidence. Data were analyzed
      using Pearson correlation, multiple regression analysis, and t tests. RESULTS:
      Fifty-seven percent of the variance in balance confidence could be explained by
      balance performance. Functional mobility and subject characteristics examined in
      this study did not contribute to balance confidence. DISCUSSION AND CONCLUSION:
      Balance performance alone is a strong determinant of balance confidence in
      community-dwelling elderly people.

PMID- 14640867
TI  - Physical therapists who claimed workers' compensation: a qualitative study.
AB  - BACKGROUND AND PURPOSE: Although most physical therapists experience work-related
      musculoskeletal disorders (WMSDs) at some time, only a small minority claim
      workers' compensation. This article describes the experiences of a group of
      therapists with WMSDs who made compensation claims. METHODS: Interviews were used
      to document the experiences of physical therapists who reported that they had
      changed their career because of WMSDs. RESULTS AND DISCUSSION: Therapists
      described their experiences in negative terms and found dealing with the workers'
      compensation system frustrating and unpleasant. They encountered attitudes that
      labeled them as malingerers and felt their credibility was questioned.
      CONCLUSIONS: Physical therapists' experiences of the workers' compensation system
      were negative, and they were keen to become independent of it. Those who claimed
      workers' compensation perceived that a compensable claim could limit their
      employment opportunities, making confidentiality an important issue when treating
      other health care professionals.

PMID- 14640868
TI  - Using clinical outcomes to explore the theory of expert practice in physical
      therapy.
AB  - BACKGROUND AND PURPOSE: Theoretical models of physical therapist expertise have
      been developed through research on physical therapists sampled solely on the
      basis of years of experience or reputation. Expert clinicians, selected on the
      basis of their patients' outcomes, have not been previously studied, nor have the
      patient outcomes of peer-nominated experts been analyzed. The purpose of our
      study was to describe characteristics of therapists who were classified as expert
      or average therapists based on the outcomes of their patients. SUBJECTS: Subjects
      were 6 therapists classified as expert and 6 therapists classified as average
      through retrospective analysis of an outcomes database. METHODS: The study was
      guided by grounded theory method, using a multiple case study design. Analysis
      integrated data from quantitative and qualitative sources and developed a
      grounded theory. RESULTS: All therapists expressed a commitment to professional
      growth and an ethic of caring. Therapists classified as expert were not
      distinguished by years of experience, but they differed in academic and work
      experience, utilization of colleagues, use of reflection, view of primary role,
      and pattern of delegation of care to support staff. Therapists classified as
      expert had a patient-centered approach to care, characterized by collaborative
      clinical reasoning and promotion of patient empowerment. DISCUSSION AND
      CONCLUSION: These findings add to the understanding of factors related to patient
      outcomes and build upon grounded theory for elucidating expert practice in
      physical therapy.

PMID- 14640869
TI  - Treadmill training for an infant born preterm with a grade III intraventricular
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Research has documented the feasibility and benefit of
      treadmill training in children with cerebral palsy and Down syndrome. The
      purposes of this case report are: (1) to determine the feasibility of treadmill
      training in an infant at high risk for neuromotor dysfunction and (2) to describe
      the child's treadmill stepping patterns following treadmill training. CASE
      DESCRIPTION: The male infant, who had a grade III intraventricular hemorrhage
      following premature birth, began physical therapy and treadmill training at 51/4
      months corrected age. Treadmill training was conducted 3 times weekly and
      videotaped weekly. Videotape analysis determined number of steps, step type, and
      foot position. OUTCOMES: Except for foot position, trends in treadmill stepping
      were similar to those of studies with infants not at high risk for neuromotor
      disabilities. DISCUSSION: This case report shows that treadmill training is
      feasible for an infant at high risk for neuromotor disabilities and may be
      associated with more mature stepping characteristics. Future research should
      evaluate optimum treadmill training parameters and long-term developmental
      outcomes.

PMID- 14640870
TI  - Understanding and treating "pusher syndrome".
AB  - "Pusher syndrome" is a clinical disorder following left or right brain damage in
      which patients actively push away from the nonhemiparetic side, leading to a loss
      of postural balance. The mechanism underlying this disorder and its related
      anatomy have only recently been identified. Investigation of patients with severe
      pushing behavior has shown that perception of body posture in relation to gravity
      is altered. The patients experience their body as oriented "upright" when the
      body actually is tilted to the side of the brain lesion (to the ipsilesional
      side). In contrast, patients with pusher syndrome show no disturbed processing of
      visual and vestibular inputs determining visual vertical. These new insights have
      allowed the authors to suggest a new physical therapy approach for patients with
      pusher syndrome where the visual control of vertical upright orientation, which
      is undisturbed in these patients, is the central element of intervention.

PMID- 14640871
TI  - The devil's in the details.

PMID- 14640872
TI  - The value of serological and genetic markers in inflammatory bowel disease;
      strength and weakness of the studies.

PMID- 14640873
TI  - HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory
      bowel disease.
AB  - HYPOTHESIS AND OBJECTIVES: the hypothesis of this study is that genes involved in
      the regulation of the immune system, expressed by HLA antigens and anti
      neutrophil cytoplasmic antibodies (ANCA), could be determinants of disease
      susceptibility and behavior in inflammatory bowel disease (IBD). MATERIAL AND
      METHOD: seventy patients with a diagnosis of inflammatory bowel disease, 46 with
      ulcerative colitis and 24 with Crohn"s disease were included. HLA class I (A and
      B) and II (DR) antigens were studied by serological techniques. Detection of ANCA
      was carried out in all patients by an indirect immunofluorescence method. The
      relative frequencies of HLA antigens were compared with a control group made up
      of 156 blood donors. The control group for the ANCA study was made up of 100
      individuals. RESULTS: we found a significant increased frequency of HLA-DR2 in
      patients with ulcerative colitis. No significant differences were found between
      patients with Crohn"s disease and controls regarding HLA typing. We detected a
      significant increase of HLA-DR3 in extensive forms of ulcerative colitis.
      Detection of ANCA was positive in 46% of the patients with ulcerative colitis and
      in 12% of the patients with Crohn"s disease (p <0.05). We observed an increased
      frequency of ANCA in patients with UC and HLA-DR2 (p = 0.15). CONCLUSIONS: the
      association found between HLA-DR3 and extensive forms of ulcerative colitis
      provides evidence of genetic heterogeneity. The relationship between ANCA and HLA
      phenotype (although not significant) supports this concept.

PMID- 14640874
TI  - [Effect of hepatic resection on development of liver metastasis].
AB  - In the early stages of metastasis, development of the disease is dependent on
      growth factors produced by the host. There are clinical situations associated
      with an increase in these factors, such as partial resection of metastasized
      liver. Given the important role of hepatotrophic factors in liver regeneration,
      we have studied the effect of partial hepatectomy on the development of residual
      micrometastases in the liver, and on the neoplastic process as a whole. We used a
      murine model in which a rabdomiosarcoma was established by subcutaneous
      inoculation of syngeneic tumor cells in male Wag rats. Subsequently, the primary
      tumor was resected and/or a 40% hepatectomy was performed. The effect of these
      two surgical procedures on the tumor process was analyzed on the 25th and 35th
      days post-inoculation, and the percentage of regenerating hepatocytes was
      assessed. Both the tumorectomy and liver resection, when not combined, produced
      an increase in regional adenopathies without modifying the evolution of
      metastasis in the liver. However, when tumor excision and partial hepatectomy
      were performed simultaneously, there was a net increase in the metastatic
      process. In addition to a rapid spread of the disease (lung, mediastinum,
      retroperitoneum), the number of liver metastases increased by 300%. This
      development coincided with a steep rise in the percentage of regenerating
      hepatocytes, which nearly doubled that of the group subjected only to liver
      resection. We conclude that liver resection, alone or combined with excision of
      the primary tumor, may enhance tumor progression, both locally and at the
      metastasic level.

PMID- 14640875
TI  - Intestinal metaplasia: evolution after Helicobacter pylori eradication and
      influence in the success of eradicating therapy.
AB  - INTRODUCTION: intestinal metaplasia associated with Helicobacter pylori infection
      is a stage of the temporal sequence of histological lesions gradually induced by
      this microorganism. It is considered a preneoplastic lesion and its regression
      after eradication is controversial. AIM: to assess the evolution of intestinal
      metaplasia after eradication and to investigate whether metaplasia is a factor
      that contributes to successful treatment. MATERIAL AND METHODS: four hundred
      Helicobacter pylori positive patients were studied. Eradicating therapy was
      administered and endoscopic biopsies of gastric antrum and body were taken before
      and after eradication. Among other histological data, the presence of intestinal
      metaplasia was assessed. RESULTS: of all patients successfully treated, biopsies
      were taken before and after eradication in 268 of them: 71 (26,5%) had metaplasia
      before and 50 (18,7%) after eradication. A significant difference was observed in
      the outcome (p = 0,036) of the first eradicating treatment between the group
      without initial metaplasia (72,7%) and the group with initial metaplasia (61.2%).
      DISCUSSION: Helicobacter pylori eradication can revert intestinal metaplasia in
      some patients. On the other hand, the first treatment could be less successful in
      patients with intestinal metaplasia.

PMID- 14640876
TI  - Helicobacter pylori and gastroesophageal reflux disease.
AB  - OBJECTIVES: 1. To determine the prevalence of Helicobacter pylori (H. pylori)
      infection in patients with gastroesophageal reflux disease (GERD), and to compare
      it with that in a control group. 2. To study the percentage of H. pylori-positive
      GERD patients according to different grades of esophagitis. MATERIAL AND METHODS:
      H. pylori prevalence by serological tests was compared among 692 patients with
      GERD and 200 healthy volunteer controls. Subsequently, the percentage of H.
      pylori was analyzed in the different grades of esophagitis, according to the
      Savary-Miller classification. RESULTS: no differences between the GERD group and
      control group were detected regarding age (50.5+/-14.7 vs 50.7+/-16.4 years, ns)
      and sex (63 vs 66% of men, ns); on the other hand the prevalence of H. pylori was
      40% in the GERD group facing 66% in the control group, p <0.01. There were no
      differences in H. pylori prevalence according to the different grades of
      esophagitis, but logistical regression analysis showed that the absence of H.
      pylori infection was associated with the presence of grade IV esophagitis.
      CONCLUSIONS: the prevalence of H. pylori infection in GERD patients is lower than
      that of the general population, and its absence is associated with more severe
      grades of the disease. These results indicate that H. pylori plays a protective
      role against GERD.

PMID- 14640877
TI  - Autoimmune cholangitis, nosological location.
AB  - Autoimmune cholangitis is an entity with a controversial nosological location. It
      has been defined as a setting of autoimmune chronic cholestasis, clinically,
      biochemically and histologically resembling primary biliary cirrhosis, although
      with a different immunological profile. It lacks antimitochondrial antibodies and
      instead usually presents other autoimmunity features, basically positivity to
      antinuclear antibodies. In this article, we discuss its nosological location
      based on descriptions published on this entity and comparisons with primary
      biliary cirrhosis.

PMID- 14640878
TI  - Role of lamivudine in the reactivation of hepatitis B virus infection in
      immunodepressed patients.
AB  - INTRODUCTION: hepatitis B virus (HBV) reactivation in immunocompromised states is
      a well-known event that may be a serious problem in endemic areas of infection.
      Presently, the investigation of hepatitis B status has been recommended prior to
      receiving cytotoxic treatment. Lamivudine has been used in the reactivation of
      HBV in immunocompromised states. We report our corresponding data for lamivudine
      in the treatment of HBV reactivation after intensive chemotherapy in patients
      with lymphoma and after kidney transplantation. CLINICAL OBSERVATION: we present
      two cases of HBV reactivation after chemotherapy for lymphoma and two cases after
      cadaveric renal transplantation treated with lamivudine (100-150 mg/day).
      RESULTS: we observed a prompt clinical improvement in all patients after
      lamivudine treatment. Furthermore, laboratory data showed a rapid biochemical and
      antiviral response. However, the response in lymphoma patients was quicker than
      in patients who had post-transplantation reactivation of HBV. Therapy was well
      tolerated and no relevant side effects appeared during follow-up (twenty four
      months). The HBV remained negative in three cases. CONCLUSION: lamivudine is
      effective and safe in the treatment of HBV reactivation in immunodepressed
      patients. Lamivudine therapy should be considered for the treatment of HBV
      reactivation in patients with prior hepatitis B or chronic hepatitis B with
      inactive viral replication.

PMID- 14640879
TI  - Cholecystocolic fistula demonstrated by barium enema: an uncommon cause of
      chronic diarrhoea.

PMID- 14640880
TI  - [Celiac colitis and ulcerative colitis].

PMID- 14640881
TI  - [Pneumoretroperitoneum in a 80 years old woman].

PMID- 14640882
TI  - Visual field representations and locations of visual areas V1/2/3 in human visual
      cortex.
AB  - The position, surface area and visual field representation of human visual areas
      V1, V2 and V3 were measured using fMRI in 7 subjects (14 hemispheres). Cortical
      visual field maps of the central 12 deg were measured using rotating wedge and
      expanding ring stimuli. The boundaries between areas were identified using an
      automated procedure to fit an atlas of the expected visual field map to the data.
      All position and surface area measurements were made along the boundary between
      white matter and gray matter. The representation of the central 2 deg of visual
      field in areas V1, V2, V3 and hV4 spans about 2100 mm2 and is centered on the
      lateral-ventral aspect of the occipital lobes at Talairach coordinates -29, -78, 
      11 and 25, -80, -9. The mean area between the 2-deg and 12-deg eccentricities for
      the primary visual areas was: V1: 1470 mm2; V2: 1115 mm2; and V3: 819 mm2. The
      sizes of areas V1, V2 and V3 varied by about a factor of 2.5 across individuals;
      the sizes of V1 and V2 are significantly correlated within individuals, but there
      is a very low correlation between V1 and V3. These in vivo measurements of normal
      human retinotopic visual areas can be used as a reference for comparison to
      unusual cases involving developmental plasticity, recovery from injury,
      identifying homology with animal models, or analyzing the computational resources
      available within the visual pathways.

PMID- 14640883
TI  - Discrimination and identification of luminance contrast stimuli.
AB  - The goal of this study was to compare luminance contrast discrimination and
      polarity identification in the inferred Parvocellular (PC-) and Magnocellular (MC
      ) pathways. The position identification task tested ability to locate a contrast
      change within a stimulus. The polarity identification task tested ability to
      classify the contrast change as either brighter or darker. Three paradigms were
      employed to find these thresholds for the inferred MC- and PC-pathways: Pulsed
      Pedestal, Steady-Pedestal and Pedestal-Delta-Pedestal. Position and polarity
      identification thresholds were the same for the Pulsed-Pedestal stimuli (inferred
      PC-pathway). The position identification thresholds were lower than the polarity
      identification thresholds for Steady-Pedestal stimuli (inferred MC-pathway). The
      position identification thresholds were lower than the polarity identification
      thresholds for Pedestal-Delta-Pedestal stimuli when the Delta-Pedestal contrast
      steps were sub-threshold or close to threshold. When the contrast steps were
      larger, position identification and polarity identification thresholds were
      similar for the Pedestal-Delta-Pedestal stimuli. Comparisons were also made
      between position identification and polarity identification thresholds for a
      short and a long stimulus presentation. There were no systematic differences
      dependent on presentation duration.

PMID- 14640884
TI  - Binocular rivalry in split-brain observers.
AB  - During binocular rivalry, visual perception switches between a stimulus viewed by
      one eye and a different stimulus viewed by the other. We studied rivalry in split
      brain observers to test two explanations. Rivalry could reflect switching of
      activity between the cerebral hemispheres, or switching by a structure in the
      right frontoparietal cortex. From these two theories, we predict no rivalry when
      stimuli are presented to a split-brain observer's left hemisphere. Yet we found
      similar rivalry from the left and right hemispheres of the split-brain observers,
      consistent with switchings being mediated by low-level processes within each
      hemisphere.

PMID- 14640885
TI  - Sensitivity for global shape detection.
AB  - In order to understand the nature of the mechanisms responsible for global shape
      detection, we measured coherence thresholds in a 2IFC task where subjects judged
      which of two arrays of Gabors contained global circular structure. The stimulus
      was composed of an array of oriented Gabor patches positioned on a polar grid.
      Thresholds were obtained for different array parameters (e.g. different area,
      density, number and positions of elements) as well as for different element
      parameters (e.g. different carrier spatial frequencies, contrasts, polarities and
      orientations). Global structure was detected when ~10% of the elements were
      coherently oriented. Neither the properties of the array (density, area, number
      or position of elements), nor those of the individual elements (carrier spatial
      frequency, contrast, polarity) altered coherence thresholds. Varying contrast or
      carrier spatial frequency within individual arrays also did not alter
      performance. Sensitivity was invariant to positional perturbations of the array
      grid. Only jittering the local orientation of elements decreased sensitivity. The
      underlying mechanisms are broadly tuned for contrast, spatial frequency and the
      spatial positioning of image samples. Detecting circular structure is a robust
      process and, in this case, a purely global one. Sensitivity was highest for
      circular as opposed to radial or spiral shapes.

PMID- 14640886
TI  - On the principle of minimal relative motion--the bar, the circle with a dot, and
      the ellipse.
AB  - Beghi, Xausa, & Zanforlin (1991a) and Beghi, Xausa, De Biasio, & Zanforlin
      (1991b) have presented visual stereokinetic phenomena. When a bar is rotated in
      the image plane, it appears to be slanted in depth. Likewise, when a circle with
      an off-centered dot is rotated, a three-dimensional (3-D) cone is perceived.
      Finally, when an ellipse is rotated in the image plane, an ellipsoid is perceived
      that is tilted in depth. To explain these phenomena, Beghi et al. (1991a,b) offer
      an analytic model that assumes that the visual system nullifies the speed
      differences between all stimulus points. I critique this analytic model, and show
      that it cannot explain the perceptual phenomena.

PMID- 14640887
TI  - Ideal observer analysis of the development of spatial contrast sensitivity in
      macaque monkeys.
AB  - To explore the factors limiting the development of visual sensitivity, we
      constructed an ideal observer model for the infant macaque visual system. We made
      measurements of retinal morphology in infant and adult macaque monkeys, and used
      the data in combination with published optical data to formulate the model. We
      compared the ideal observer's ability to detect low-contrast gratings presented
      either in isolation or in spatiotemporal noise with behavioral data obtained
      under matched conditions. The ideal observer showed some improvement in visual
      performance up to the age of 4 weeks, but little change thereafter. Behavioral
      data show extensive changes over the ages 5-50 wk, after the ideal observer's
      performance has become asymptotic. We conclude that the development of visual
      sensitivity in infant monkeys is not limited by changes in the front-end factors
      captured by the ideal observer model, at least after the age of 5 weeks. Using
      noise masking, we also estimated the variability of neural processing in
      comparison with the photon noise-limited ideal. We found that both additive and
      multiplicative components of this variability are elevated in infant monkeys, and
      improve (though not to ideal levels) during development. We believe that these
      changes all reflect maturation of visual processing in cortical circuits, and
      that no aspect of visual performance in the regime we studied is limited by the
      properties of the retina and photoreceptors, either in infant or in adult
      animals.

PMID- 14640888
TI  - Pathophysiological and clinical importance of insulin-like growth factor-I with
      respect to bone metabolism.
AB  - The modern concept of causality of diseases emphasizes the study of natural
      defense functions of the organism and possibilities of influencing them, which
      will lead to effective prevention of these diseases. A great deal of information
      has been obtained on the system growth hormone (GH)/insulin-like growth factor
      (IGF)-I, which is of quite fundamental importance for the integrity of the
      organism. An imbalance of the system may be the cause of diseases of the neonatal
      period, as well as diseases associated with aging. In old age, the synthesis of
      the crucial peptide system, IGF-I, declines as well as the sensitivity of tissues
      to this hormone. At the same time the changes in the expression of IGF-binding
      proteins (IGFBP) occur. Systemic growth factors are present in measurable
      concentrations in the circulation, they are, however, taken up or synthesized by
      some tissues, where they act as local cellular regulators. IGF-I is produced by
      many tissues, including bones under the control of estrogens, growth hormone and
      the parathyroid hormone. A decline of bone IGF-I in the cortical portion of bones
      is one of the many mechanisms leading to the development of involutional
      osteoporosis. Correlation studies, which have provided evidence of a relationship
      between the IGF system and the building of peak bone mass and its subsequent loss
      contributed to the understanding of the pathogenesis of this disease. It may be
      foreseen that the results of intervention studies focused on the effects of the
      recombinant IGF-I will also influence therapeutic and preventive approaches.
      Modern antiresorption pharmacotherapy stabilizes or enhances bone density and
      reduces the risk of fractures. The addition of effective anabolics might increase
      the effectiveness of treatment by shifting the remodeling equilibrium in favor of
      formative processes. Because both recombinant GH and IGF-I have certain
      therapeutic limitations, it is considered to utilize substances which either
      stimulate endogenous IGF-I production directly in the bone or modulate synthesis
      and distribution of binding proteins for the peptide. Further new findings
      related to physiology and pathophysiology of this peptide will contribute to
      designing new strategies in the prevention of osteoporosis and other serious
      diseases of old age, such as diabetes, neoplasias or cardiovascular diseases.

PMID- 14640889
TI  - Transgenic expression of CD36 in the spontaneously hypertensive rat is associated
      with amelioration of metabolic disturbances but has no effect on hypertension.
AB  - Spontaneously hypertensive rats (SHR/NIH strain) harbor a deletion variant in the
      Cd36 fatty acid transporter and display defective fatty acid metabolism, insulin
      resistance and hypertension. Transgenic rescue of Cd36 in SHR ameliorates insulin
      resistance and improves dyslipidemia. However, the role of Cd36 in blood pressure
      regulation remains controversial due to inconsistent blood pressure effects that
      were observed with transgenic expression of Cd36 on the SHR background. In the
      current studies, we developed two new SHR transgenic lines, which express wild
      type Cd36 under the control of the universal Ef-1 alpha promoter, and examined
      the effects of transgenic expression of wild type Cd36 on selected metabolic and
      cardiovascular phenotypes. Transgenic expression of Cd36 in the new lines was
      associated with significantly decreased serum fatty acids, amelioration of
      insulin resistance and glucose intolerance but failed to induce any consistent
      changes in blood pressure as measured by radiotelemetry. The current findings
      confirm the genetic association of defective Cd36 with disordered insulin action
      and fatty acid metabolism in the SHR/NIH strain and suggest that Cd36 is linked
      to other gene(s) on rat chromosome 4 that regulate blood pressure.

PMID- 14640890
TI  - Gender-specific genetic determinants of blood pressure and organ weight:
      pharmacogenetic approach.
AB  - A total genome scan and pharmacogenetic study were designed to search for genetic
      determinants of blood pressure (BP) as well as heart and kidney weights. Genome
      scanning was carried out in 266 F(2) intercrosses from Prague hypertensive
      hypertriglyceridemic rats for phenotypes of organ weights, baseline BP, BP after
      blockade of the renin-angiotensin system (RAS) by losartan, of the sympathetic
      nervous system (SNS) by pentolinium, and of the nitric oxide (NO) synthase by
      N(G)-nitro-L-arginine methyl ester. Pharmacogenetic analysis showed that, in
      males, BP was controlled by two loci on chromosomes 1 and 5 (Chr1, Chr5) through
      the SNS, and these loci showed a positive contribution for relative kidney weight
      (KW/BW). On the other hand, baseline BP in females was controlled by two loci on
      Chr3 and Chr7. The effect of these loci was not mediated by the RAS, SNS or NO
      system. These loci did not show any effect for KW/BW. Negatively-linked loci for
      KW/BW and relative heart weight (HW/BW) were identified on Chr2 in both genders.
      Another negatively-linked locus for KW/BW, located on Chr8 in males, affected BP
      through the SNS. This locus on Chr8 overlapped with a previously-reported
      modifier locus for polycystic kidney disease (PKD). In conclusion, this
      pharmacogenetic study determined two loci for BP and relative organ mass
      implicating sympathetic overactivity. Concordance of the identified locus for
      KW/BW and BP through the SNS on Chr8 with the PKD locus revealed the importance
      of this region for renal complications in various diseases.

PMID- 14640891
TI  - Cardiac effects of endothelin-1 (ET-1) and related C terminal peptide fragment:
      increased inotropy or contribution to heart failure?
AB  - The contrasting pattern of cardiac inotropy induced by human peptide endothelin-1
      (ET-1) has not been satisfactorily explained. It is not clear whether ET-1 is
      primarily responsible for increased myocardial ET-1 expression and release with
      resultant inotropic effects, or for the induction of myocardial hypertrophy and
      heart failure. There are at least two subtypes of endothelin receptors (ET(A) and
      ET(B)) and the inotropic effects of ET-1 differ depending on the receptor
      involved. Along with some other groups, we reported significant subtype-ET(B)
      endothelin receptor down-regulation in human cardiac cells preincubated with
      endothelin agonists (Drimal et al. 1999, 2000). The present study was therefore
      designed to clarify the subtype-selective mechanisms underlying the inotropic
      response to ET-1 and to its ET(B)-selective fragment (8-21)ET-1 in the isolated
      rat heart. The hearts were subjected to (1-21)ET-1 and to (8-21)ET-1, or to 30
      min of stop-flow ischemia followed by 40 min of reperfusion, both before and
      after selective blockade of endothelin receptors. The present study revealed that
      both peptides, ET-1 and its (8-21)ET-1 fragment, significantly reduced coronary
      blood flow in nmolar and higher concentrations. The concomitant negative inotropy
      and chronotropy were marked after ET-1, while the infusion of the ET-1(8-21)
      fragment produced a slight but significant positive inotropic effect. Among the
      four endothelin antagonists tested in continuous infusion only the non-selective
      PD145065 and ET(B1/B2) selective BQ788 (in molar concentrations) slightly reduced
      the early contractile dysfunction of the heart induced by ischemia, whereas ET(A)
      selective PD155080 partially protected the rat heart on reperfusion.

PMID- 14640892
TI  - Long-term effect of molsidomine and pentaerythrityl tetranitrate on
      cardiovascular system of spontaneously hypertensive rats.
AB  - We studied the effects of long-term administration of molsidomine and
      pentaerythrityl tetranitrate (PETN) on the cardiovascular system of spontaneously
      hypertensive rats (SHR). One control and three experimental groups of 10-week-old
      animals were used: 1) control Wistar rats, 2) SHR, 3) SHR treated with
      molsidomine in tap water (100 mg/kg/day, by gavage), and 4) SHR treated with PETN
      in tap water (200 mg/kg/day, by gavage). After six weeks, the content of cGMP in
      platelets and NO synthase (NOS) activity in aortas were evaluated in the
      experimental groups. For morphological evaluation the rats were perfused at 120
      mm Hg with a glutaraldehyde fixative and the arteries were processed for electron
      microscopy. Blood pressure and heart weight/body weight ratio (HW/BW) were
      increased in all experimental groups with respect to the controls. HW/BW was
      lower in the molsidomine group in comparison to both SHR and PETN-treated group.
      The platelet content of cGMP was increased and the activity of NOS in the aortas
      was decreased in the molsidomine and PETN-treated groups. Wall thickness and
      cross-sectional area of thoracic aorta, carotid artery and coronary artery were
      increased similarly in all experimental groups compared to the controls, but
      there were no differences among the experimental groups. We summarize that long
      term administration of exogenous NO donors did not improve pathological changes
      of the cardiovascular system in SHR.

PMID- 14640893
TI  - Tissue factor, tissue factor pathway inhibitor and cytoadhesive molecules in
      patients with an acute coronary syndrome.
AB  - The tissue factor plays a crucial role in initiating blood coagulation after
      plaque rupture in patients with acute coronary syndrome. It is abundant in
      atherosclerotic plaques. Moreover, P-selectin, some cytokines, endotoxin and
      immune complexes can stimulate monocytes and induce the tissue factor expression
      on their surface. The aim of the study was to compare plasma levels of the tissue
      factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 in
      patients with acute myocardial infarction, unstable angina pectoris, stable
      coronary artery disease and normal control subjects. In addition, plasma levels
      of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and
      ICAM-1 were measured in the blood withdrawn from the coronary sinus in a subgroup
      of patients with unstable angina pectoris and stable coronary artery disease in
      which the difference between concentrations in the coronary sinus and systemic
      blood was calculated. A significant increase in tissue factor pathway inhibitor
      plasma levels was detected in patients with acute myocardial infarction (373.3+/
      135.1 ng/ml, p<0.01) and unstable angina pectoris (119.6+/-86.9 ng/ml, p<0.05) in
      contrast to the patients with stable coronary artery disease (46.3+/-37.5 ng/ml)
      and normal subjects (45.1+/-14.3 ng/ml). The plasma levels of tissue factor
      pathway inhibitor were significantly increased both in the coronary sinus and
      systemic blood in the patients with unstable angina pectoris. There was only a
      non-significant trend to higher plasma levels of the tissue factor in patients
      with acute myocardial infarction and unstable angina pectoris as compared to the
      patients with stable coronary artery disease and normal subjects, the values
      being 129.1+/-30.2 pg/ml, 130.5+/-57.8 pg/ml, 120.2+/-45.1 pg/ml and 124.9+/-31.8
      pg/ml, respectively. Plasma levels of soluble P-selectin was only slightly, but
      non-significantly higher in patients with unstable angina pectoris and stable
      coronary artery disease (184.2+/-85.4 ng/ml and 201.6+/-67.9 ng/ml, respectively)
      than in patients with the acute myocardial infarction (157.4+/-88.4 ng/ml) or
      normal subjects (151.4+/-47.1 ng/ml). The difference in plasma levels of soluble
      ICAM-1 between the blood withdrawn from the coronary sinus and systemic
      circulation correlated significantly with the corresponding difference in plasma
      levels of soluble P-selectin and E-selectin. In conclusion, the tissue factor and
      the tissue factor pathway inhibitor play a crucial role in the initiation of
      arterial thrombosis. The tissue factor pathway inhibitor levels are increased
      both in the systemic blood and in the coronary sinus of patients with the acute
      coronary syndrome.

PMID- 14640894
TI  - The influence of nitric oxide synthase inhibitor L-NAME on bones of male rats
      with streptozotocin-induced diabetes.
AB  - The pathophysiological processes underlying the development of diabetic
      osteopenia has not hitherto been elucidated. Induction of streptozotocin diabetes
      leads in our experiments to decrease of bone density, ash, mineral content and to
      thinner cortical width compared to control male rats. In order to investigate the
      pathogenetic role of bone resorption by osteoclasts in streptozotocin-induced
      diabetes, we determined the circulating levels of tartrate-resistant acid
      phosphatase (TRAP), a biochemical marker for bone resorption. Plasma TRAP values
      in diabetic rats did not differ from their corresponding controls. Streptozotocin
      diabetes by itself did not have any effect on the weight of seminal vesicles
      which are highly testosterone-dependent. Low doses of nitric oxide cause bone
      resorption, but higher doses of NO inhibit bone resorbing activity. We examined
      the effect of L-NAME (inhibitor of nitric oxide production) after six weeks of
      administration to diabetic rats. There was no further significant loss of bone
      mineral density, ash and mineral content or tibia weight in diabetic rats treated
      with L-NAME. L-NAME itself did not decrease bone metabolism. In our study no
      evidence of an increased bone resorption was found. Our results have indicated
      that a predominance of bone resorption over bone formation is not involved in the
      pathogenesis of diabetes-associated osteopenia. Inhibition of NO neither
      increased osteoclastic activity (TRAP) nor induced osteopenia in L-NAME-treated
      rats. This suggests a possibility that NO is not involved in the pathogenesis of
      diabetic osteopenia.

PMID- 14640895
TI  - Diabetes-induced biochemical changes in central and peripheral catecholaminergic
      systems.
AB  - A great variety of alterations have been described in the nervous system of
      diabetic animals. They are named as diabetic neuropathy and affect the brain,
      spinal cord and peripheral nerves. In diabetic animals, plasma and tissue
      catecholamine levels have been reported to be increased, decreased or unchanged,
      and these disparities have been explained by differences in the tissues selected,
      severity or duration of diabetes. Dopamine, norepinephrine and epinephrine from
      different tissues were extracted by absorption onto alumina, and measured by high
      performance liquid chromatography with electrochemical detection. We found that
      diabetes alters catecholaminergic systems in a highly specific manner. The
      dopamine content is reduced in the dopaminergic nigrostriatal system only.
      Norepinephrine is differently altered in several areas of the sympathetic nervous
      system. It is increased in cardiac ventricles, and decreased in stellate ganglia
      and the blood serum. However, it is not altered in the central nervous system.
      Finally, epinephrine is only altered in the adrenal gland where it is increased,
      and in the serum where it is reduced. Our results suggest that diabetes reduces
      the activity of the nigrostriatal dopaminergic system. Changes found at the
      sympathoadrenal level could be explained by reduced norepinephrine and
      epinephrine synthesis, with increased storage due to a reduced release from
      synaptic vesicles.

PMID- 14640896
TI  - Estrogen effect on some enzymes in female rats after downhill running.
AB  - The study investigates the effect of administered estrogen on plasma creatine
      kinase (CK) and lactate dehydrogenase (LD) levels in female ovariectomized rats
      after downhill running. Rats ovariectomized before sexual maturity were
      subcutaneously implanted with pellets containing 17 beta-estradiol or placebo.
      Three weeks later they were subjected to a 90-min intermittent downhill running
      protocol. Blood samples were obtained from the jugular vein immediately after and
      72 h after exercise for determination of plasma CK, LD and 17 beta-estradiol
      levels. A two-way analysis of variance was used for data evaluation. Plasma CK
      and LD levels were significantly lower (p<0.05) in the estrogen-supplemented,
      ovariectomized animals which suggests that less muscle damage occurred compared
      to the controls immediately and 72 h after exercise. Estrogens may have a
      protective effect on muscle tissue possibly due to their antioxidant and membrane
      stabilizing properties.

PMID- 14640897
TI  - Activity of the laryngeal abductor and adductor muscles during cough, expiration
      and aspiration reflexes in cats.
AB  - We studied the temporal relationships and the patterns of electromyographic
      activities of the posterior cricoarytenoid and thyreoarytenoid muscles (laryngeal
      abductor and adductor), the diaphragm and abdominal muscles in anesthetized cats
      during mechanically induced tracheobronchial and laryngopharyngeal coughs,
      expiration and aspiration reflexes. The posterior cricoarytenoid muscle activity
      reached the maxima just before the peak of diaphragmatic activity in both types
      of cough and aspiration reflexes and slightly before the top of abdominal muscle
      activity in coughs and the expiration reflex. Thus, this muscle contributes to
      the inspiratory phase of coughs and aspiration reflex and also to the expulsive
      phase of coughs and the expiration reflex. The thyreoarytenoid muscle presented
      strong discharges in the compressive phase of coughs and expiration reflex
      (during the rising part of the abdominal muscle activity) and in the subsequent
      laryngoconstriction (following the diaphragmal and/or abdominal muscle activity)
      in all four reflexes. This muscle was also slightly activated at the beginning of
      the aspiration reflex. The existence of four phases of the cough reflex is also
      discussed.

PMID- 14640898
TI  - Hyperoxia prevents carrageenan-induced enlargement of functional residual lung
      capacity in rats.
AB  - Experimental pneumonia induced by intratracheal application of carrageenan or
      paraquat increases the functional residual lung capacity (FRC) in rats. The
      mechanism of this increase is not clear, but a decrease in PO(2) may be involved.
      To test this possibility, we attempted to eliminate the PO(2) decrease in
      carrageenan-treated rats by exposing them to hyperoxia. Animals of the first
      group were exposed to 7 days of hyperoxia (F(I)O(2) 0.78-0.84, group Car+O(2))
      after intratracheal application of carrageenan (0.5 ml of 0.7 % carrageenan in
      saline), whereas animals of the second group were given the same dose of
      carrageenan but breathed air (group Car+A). The third group of rats was kept for
      seven days in hyperoxia (group O(2)) and the fourth group served as controls (C).
      The animals were then anesthetized and intubated and their ventilatory parameters
      and FRC were measured during air breathing. Carrageenan application induced a FRC
      increase (Car+A 2.0+/-0.2 ml, C 1.6+/-0.1 ml), which was not seen in carrageenan
      treated rats exposed to hyperoxia (Car+O(2) 1.6+/-0.1 ml). Hyperoxia alone did
      not affect the value of FRC (O(2) 1.5+/-0.1 ml). These results support the
      hypothesis that a decrease in PO(2) plays an important role in the carrageenan
      induced increase of FRC in rats.

PMID- 14640899
TI  - Vegetable oils used as vitamin E vehicle affect the electrical activity of the
      rat heart.
AB  - The aim of this study is to define the possible effects of vegetable oils used as
      vitamin E vehicle on the electrical activity of the rat heart. To test the
      possible effects of vitamin E vehicles we studied the effect of i.p. injected
      corn oil, hazelnut oil or peanut oil on the action potential parameters recorded
      in both papillary and left atrial muscle strips. Four experimental groups were
      used. The control group was injected (i.p.) with distilled water, while the three
      remaining groups received injections of corn oil, hazelnut oil, or peanut oil for
      five weeks (in a dose of 0.4 ml/kg/day--minimum amount of oil in which vitamin E
      could be dissolved). We used borosilicated (15-20 megaohms) capillary electrodes
      and intracellular action potentials (AP) were recorded in isolated papillary and
      left atrium muscle strips. While administration of three different types of
      vegetable oil had no significant effect on AP parameters of papillary muscle,
      they significantly prolonged the repolarization phase of AP in atrial strips.
      These results show that vegetable oils used as vitamin E vehicles may alter the
      electrical activity of the heart in a tissue-dependent manner. The present data
      indicate that the possible effect of vegetable oil vehicles should be kept in
      mind while evaluating the possible effects of in vivo vitamin E administration.

PMID- 14640900
TI  - Effect of quercetin on daunorubicin-induced heart mitochondria changes in rats.
AB  - Cancer therapy with daunorubicin is limited by its cardiotoxicity. It has been
      suggested that daunorubicin-induced free radical generation can be involved. The
      precise molecular mechanism of daunorubicin-induced cardiotoxicity is still not
      well understood but it is believed that mitochondria play an important role in
      this process. It has been reported that flavonoids with antioxidant properties
      may prevent anthracycline-induced cardiotoxicity. In this work, we investigated
      the effects of daunorubicin and quercetin on mitochondrial enzyme activities such
      as ATPase, glutathione peroxidase (GPx) and glutathione reductase (GR). Moreover,
      we also studied the changes of outer mitochondrial membrane using synchronous
      fluorescence spectra. The activity of ATPase and GR were significantly increased
      after daunorubicin application. Pretreatment with quercetin significantly
      alleviated this increase. On the other hand, GPx activity was significantly
      decreased and quercetin prevented this decrease. Treatment with quercetin alone
      had no significant effect on the enzyme activity studied. Quercetin also
      completely prevented daunorubicin-induced changes in fluorescence of the outer
      mitochondrial membrane. In conclusion, our data indicate that quercetin may be
      useful in mitigating daunorubicin-induced cardiotoxicity.

PMID- 14640901
TI  - Polarographic evaluation of mitochondrial enzymes activity in isolated
      mitochondria and in permeabilized human muscle cells with inherited mitochondrial
      defects.
AB  - Inherited disturbances of the mitochondrial energy generating system represent a
      heterogeneous group of disorders associated with a broad spectrum of metabolic
      abnormalities and clinical symptoms. We used the polarographic and
      spectrophotometric method for detection of mitochondrial disorders, because these
      two techniques provide a different insight into mitochondrial function. In six
      patients suspected of mitochondrial disease we found defects of complex I (two
      patients), complex III (one patient), complex IV (two patients) and a combination
      of defect of complex III and IV (one patient). Citrate synthase activity, used as
      the reference enzyme, was not changed. A comparison of the two methods showed
      several differences in evaluation of mitochondrial enzymes activity due to the
      fact that both methods used different conditions for enzyme activity
      measurements. In contrast to oxygen consumption measurements, where the function
      of the whole-integrated respiratory chain is characterized, spectrophotometric
      measurements characterize activities of isolated complexes in disintegrated
      membranes. However, it may be concluded from our experiments that both methods
      provide useful and complementary data about mitochondrial energetic functions.
      Whereas spectrophotometric data are suitable for evaluation of maximal enzyme
      activities of mitochondrial enzyme complexes, polarographic data provide better
      information about enzyme activities in cells with mitochondrial defects under in
      situ conditions.

PMID- 14640902
TI  - Several functions of immune cells in mice changed by oxidative stress caused by
      endotoxin.
AB  - We have studied natural killer (NK) activity, lymphoproliferative response, the
      release of several cytokines (IL-2, TNF alpha and IL-1 beta) and the ROS
      production in peritoneal leukocytes obtained 0, 2, 4, 12 and 24 h after
      lipopolysaccharide (LPS) injection. Lethal septic shock (100 % mortality occurred
      at 30 h after LPS administration) was caused in female BALB/c mice by
      intraperitoneal injection of 100 mg/kg of E. coli LPS. Cytotoxicity and
      lymphoproliferation assay were preformed together with the measurement of IL-1
      beta, IL-2 and TNF alpha production, and quantification of ROS. Natural killer
      activity, spontaneous lymphoproliferative response, IL-2, TNF alpha, IL-beta
      release and ROS production were increased after LPS injection. In conclusions,
      ROS and proinflammatory mediators produced by immune cells in response to LPS are
      involved in the oxidative stress of endotoxic shock. This oxidative state alters
      some functional characteristics of leukocytes (proliferation and NK activity).

PMID- 14640904
TI  - Kynurenic acid prevented social recognition deficits induced by MK-801 in rats.
AB  - MK-801 impaired social recognition potency of adult male rats when given
      immediately after the initial interaction with a juvenile rat. Administration of
      kynurenic acid prior to the initial interaction protected the adults against
      recognition deficits induced by MK-801. When re-exposed at a delay of 30 min to
      the familiar juvenile, social investigation in the adults was significantly
      reduced. Thus, the adults are able to remember olfactory stimuli emitted by
      juvenile con-specifics.

PMID- 14640903
TI  - Ecto-ATPase and ecto-ATP-diphosphohydrolase are co-localized in rat hippocampal
      and caudate nucleus synaptic plasma membranes.
AB  - Enzymes that hydrolyze extracellular ATP, i.e. ecto-ATPase and ecto-ATP
      diphosphohydrolase (ATPDase), can be differentiated by ability of the latter to
      hydrolyze ADP and by slightly different kinetic properties of the two enzymes.
      Synaptic plasma membrane fractions isolated from rat hippocampus and caudate
      nucleus exhibit ADP-hydrolyzing activity, as revealed by the enzyme assay, and
      the presence of ecto-ATPase protein, as revealed by immunological identification
      on Western blot. These findings indicate that both enzymes are co-expressed in
      the synaptic membrane compartment of hippocampal and caudate nucleus neurons.
      Kinetic analysis was performed to determine the relative contribution of each
      enzyme to the total ATP-hydrolyzing activity, while an inhibition study was
      carried out in order to exclude the interference of other nonspecific ATPase and
      phosphatase activities. Based on the kinetic properties, sensitivity to
      inhibitors and V(ATP)/V(ADP) ratio of about 2, we concluded that a substantial
      portion of ATP-hydrolyzing activity in both synaptic membrane preparations can be
      ascribed to the catalytic action of ATPDase. On the other hand, the highest
      catalytic efficacy when ATP is the substrate and the greater abundance of ecto
      ATPase protein in caudate nucleus preparation suggest that the relative
      contribution of ecto-ATPase to the total ATP-hydrolyzing activity in the caudate
      nucleus is higher than in the hippocampus.

PMID- 14640905
TI  - N-methyl-D-aspartate prevented memory deficits induced by MK-801 in mice.
AB  - An interaction between N-methyl-D-aspartate (NMDA) and MK-801 was examined in
      mice using a modified elevated plus-maze paradigm that allows assessment of the
      adaptive form of spatial memory. NMDA administered (s.c.) immediately after the
      acquisition session protected the animals against the amnesia induced by MK-801
      given shortly before the retention session. Behavioral performance, expressed as
      the transfer latency, and therefore spatial memory potency of NMDA plus MK-801
      treated animals was comparable with that of both NMDA-treated animals and the
      controls.

PMID- 14640906
TI  - Epigenetic transitions: towards therapeutic targets.
AB  - Therapeutic approaches aimed at developing epigenetically-effective drugs are
      under intense investigation. Several classes of enzymes regulating histone
      acetylation and DNA methylation, which are required for epigenetic transitions,
      offer attractive targets for therapeutic interventions. Imbalances in histone
      acetylation and DNA methylation may play a significant role in the development of
      cancer and leukaemia and may provide a mechanistic rationale for targeting
      epigenetic modifications. Clinical trials designed to evaluate inhibitors of DNA
      methylation and histone deacetylase inhibitors are showing encouraging results in
      cancer patients. A growing quantity of data from preclinical research supports
      the notion that epigenetically-effective drugs could also find an application in
      other therapeutic areas. A number of emerging biomarkers may prove useful for
      monitoring drug effects and defining molecular signatures of response, toxicity
      and effective dose.

PMID- 14640907
TI  - Pathophysiological roles for IL-18 in inflammatory arthritis.
AB  - IL-18 is a unique cytokine with prominently wide spectrum biological actions.
      Among these, its IFN-gamma/TNF-alpha-inducing activity primarily contributes to
      the development of various inflammatory diseases including inflammatory
      arthritis. IL-18 levels correlate with the disease activity of rheumatoid
      arthritis (RA) and osteoarthritis (OA). IL-18 is spontaneously released from RA
      synovial cells and OA chondrocytes and seems to participate in the development of
      the inflammatory and destructive alterations of joints via induction of TNF
      alpha, a potent effector molecule. TNF-alpha, in turn, increases IL-18 expression
      in RA synovial cells. Recent clinical trials have revealed the efficacy of TNF
      alpha in RA with a reduction in circulatory IL-18 levels. These may implicate the
      positive circuit between IL-18 and TNF-alpha for development of RA. As IL-18
      deficient mice evade collagen-induced arthritis in a mouse RA model, therapeutics
      targeting IL-18 may be beneficial against RA/OA. Here, the authors review the
      possible roles of IL-18 in inflammatory arthritis.

PMID- 14640908
TI  - Novel therapeutic targets in Helicobacter pylori.
AB  - The failure of current regimens to treat the gastric pathogen Helicobacter pylori
      is a growing problem. Responsible for gastritis and peptic ulcer disease, and
      designated as a Class 1 carcinogen, its presence in up to 90% of the population
      of the developing world makes its treatment a primary concern. The use of
      genomic, proteomic and transcriptomic data to determine essential gene products
      as targets for novel therapeutic agents is of key interest in this research. This
      review describes how such data can be obtained, evaluated and eventually used as
      a basis for the development of both vaccine and novel anti-helicobacter agents.
      It indicates both past successes and possible new avenues to exploit the
      increased availability of such data, whilst also examining the limitations of
      such approaches.

PMID- 14640910
TI  - Cannabinoid receptor systems: therapeutic targets for tumour intervention.
AB  - The past decade has witnessed a rapid expansion of our understanding of the
      biological roles of cannabinoids and their cognate receptors. It is now certain
      that Delta9-tetrahydrocannabinol, the principle psychoactive component of the
      Cannabis sativa plant, binds and activates membrane receptors of the 7
      transmembrane domain, G-protein-coupled superfamily. Several putative
      endocannabinoids have since been identified, including anandamide, 2-arachidonyl
      glycerol and noladin ether. Synthesis of numerous cannabinomimetics has also
      greatly expanded the repertoire of cannabinoid receptor ligands with the
      pharmacodynamic properties of agonists, antagonists and inverse agonists.
      Collectively, these ligands have proven to be powerful tools both for the
      molecular characterisation of cannabinoid receptors and the delineation of their
      intrinsic signalling pathways. Much of our understanding of the signalling
      mechanisms activated by cannabinoids is derived from studies of receptors
      expressed by tumour cells; hence, this review provides a succinct summary of the
      molecular pharmacology of cannabinoid receptors and their roles in tumour cell
      biology. Moreover, there is now a genuine expectation that the manipulation of
      cannabinoid receptor systems may have therapeutic potential for a diverse range
      of human diseases. Thus, this review also summarises the demonstrated antitumour
      actions of cannabinoids and indicates possible avenues for the future development
      of cannabinoids as antitumour agents.

PMID- 14640909
TI  - The therapeutic potential of neuronal KCNQ channel modulators.
AB  - Neuronal KCNQ (Kv7) channels (KCNQ2-5 or Kv7.2-7.5, disclosed to date) were
      discovered by virtue of their homology with a known cardiac channel involved in
      long QT syndrome (KvLQT or KCNQ1, Kv7.1) and first disclosed in 1998. The
      involvement of KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) in a benign idiopathic neonatal
      epilepsy, KCNQ4 (Kv7.4) in a form of congenital deafness, and the discovery that
      neuronal KCNQ heteromultimers were among the molecular substrates of M-channels,
      resulted in a high level of interest for potential drug development strategies. A
      number of small-molecule modulators were quickly identified, including openers or
      activators such as the antiepileptic drug candidate retigabine and the
      structurally-related analgesic drug flupirtine (Katadolon trade mark Asta
      Medica), and a group of KCNQ channel inhibitors/blockers originally developed for
      cognition enhancement. All of these data have suggested a rich target profile for
      modulators of neuronal KCNQ channels, including a variety of neuronal
      hyperexcitability disorders and conditions for openers, such as the epilepsies,
      acute pain, neuropathic pain, migraine pain and some neurodegenerative and
      psychiatric disorders. KCNQ blockers could likewise have utility in disorders
      characterised by neuronal hypoactivity, including cognition enhancement and
      perhaps disorders of mood. Emerging patent literature suggests significant
      interest in neuronal KCNQ modulation in the pharmaceutical industry and
      significant chemical diversity concerning KCNQ modulation.

PMID- 14640911
TI  - Cancer target discovery using SAGE.
AB  - Cancer is a genetic disease. Genetic events including mutations, chromosomal
      gains, losses and rearrangements, along with epigenetic alterations, lead to
      significant transcriptional changes in cancer cells. Changes in the expression of
      many genes associated with the onset and progression of cancer likely contribute
      to the cancerous phenotype. SAGE (Serial Analysis of Gene Expression) is an
      expression profiling method that allows for global, unbiased and quantitative
      characterisation of transcriptomes. The expression of thousands of genes can be
      analysed simultaneously without prior knowledge of their sequence, thus leading
      to the discovery of novel transcripts. In addition to characterising normal and
      malignant gene expression patterns, SAGE can be used to identify downstream
      targets of tumour suppressors and oncogenes and further annotate genomes.
      Comprehensive analyses of expression profiles using SAGE will yield many new
      diagnostic and prognostic markers as well as therapeutic targets in cancer.

PMID- 14640912
TI  - 11beta-hydroxysteroid dehydrogenase type 1 as a novel therapeutic target in
      metabolic and neurodegenerative disease.
AB  - 11beta-hydroxysteroid dehydrogenase Type 1 (11HSD1) catalyses regeneration of
      active 11-hydroxy glucocorticoids from inactive 11-keto metabolites within target
      tissues. Inhibition of 11HSD1 has been proposed as a novel strategy to lower
      intracellular glucocorticoid concentrations, without affecting circulating
      glucocorticoid levels and their responsiveness to stress. Increased 11HSD1
      activity may be pathogenic, for example, in adipose tissue in obesity.
      Experiments in transgenic mice and using prototype inhibitors in humans show
      benefits of 11HSD1 inhibition in liver, adipose and brain tissue in treating
      features of the metabolic syndrome and cognitive dysfunction with ageing. The
      clinical development of potent selective 11HSD1 inhibitors is now a high
      priority.

PMID- 14640913
TI  - Replacement therapy in Addison's disease.
AB  - Addison's disease or primary adrenal insufficiency is a rare disease, which is
      usually caused by autoimmune destruction of the adrenal cortex. The clinical
      picture is caused by deficiency of cortisol and aldosterone. These deficiencies
      are accompanied by adrenal androgen depletion of yet unknown significance. The
      current therapy is the replacement of glucocorticoids and mineralocorticoids, but
      the available drugs do not restore the normal diurnal variations in serum hormone
      levels. The clinical consequences of the grossly unphysiological replacement
      therapy are largely unknown. Many patients with Addison's disease on standard
      replacement therapy complain of fatigue, weariness, and reduced stress tolerance.
      One particular concern has been negative effects on both bone metabolism due to
      over-replacement of glucocorticoids and androgen depletion. This review discusses
      the evidence for the current drug and dosage recommendations. Current recommended
      daily starting dose for hydrocortisone and cortisone acetate are 20 and 25 mg,
      respectively, divided into two or preferably three doses. The mineralocorticoid
      depletion should be treated with fludrocortisone 0.05-2.0 mg/day [DOSAGE ERROR
      CORRECTED]. Replacement of dehydroepiandrosterone 20-50 mg has been advocated in
      adrenal failure, but the evidence for benefit is weak.

PMID- 14640914
TI  - Systemic chemotherapy for squamous cell head and neck cancer.
AB  - Squamous cell head and neck cancer is a relatively uncommon malignancy in North
      America. Nonetheless, it has been of considerable interest to medical oncologists
      because of its remarkable sensitivity to systemic chemotherapy. Even in patients
      with relapsed or metastatic disease, meaningful tumour shrinkage can be achieved
      with systemic therapy. This has led to the performance of carefully conducted
      clinical trials exploring the role of systemic chemotherapy, not only in the
      palliative setting, but as part of definitive multi-modality treatment.
      Chemotherapy has been used as the initial (or induction) treatment, as an
      adjuvant treatment after definitive surgery and/or radiation, and concurrent with
      both definitive and adjuvant radiation therapy. Evidence-based conclusions have
      been drawn from these clinical trials and have led to significant changes in the
      current standards of care for this disease. In this article, the available data
      supporting the use of systemic chemotherapy as palliative treatment, and as part
      of the definitive management for this disease will be reviewed.

PMID- 14640916
TI  - Pharmacotherapy of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the more common causes of cancer death
      worldwide. It occurs on a background of chronic liver disease or viral hepatitis
      in the vast majority of cases, with hepatitis C being mostly responsible for its
      continuing rise in western countries. With the screening of at-risk groups, up to
      70% of HCC lesions will be detected at a treatable stage but at best, only 20-30%
      will benefit from potentially curative hepatic resection or transplantation. How
      best to treat the remaining nonsurgical patients is an area of much debate and no
      ideal treatment is yet available. This review summarises some of the therapeutic
      modalities used for HCC, with an emphasis on pharmacological therapies.

PMID- 14640915
TI  - Effectiveness of chemotherapy in rhabdomyosarcoma: example of orbital primary.
AB  - The survival of patients with rhabdomyosarcoma has been progressively improved
      with successive protocols due to the development of multidisciplinary management
      and the data accumulated by international groups. Orbital rhabdomyosarcoma
      represents 10% of all cases and affects young children (median age: 6.8 years).
      It is a chemosensitive and radiosensitive tumour. Chemotherapy is designed to
      decrease the indications for local therapy (mainly radiotherapy) responsible for
      a high rate of sequelae (cosmetic, functional or secondary cancer). According to
      the International Society of Paediatric Oncology guidelines, local therapy is not
      indicated as first-line treatment in case of complete remission after
      chemotherapy. The 10-year survival of children with non-parameningeal orbital
      rhabdomyosarcoma is currently 87% and identical survivals are reported by the
      various collaborative groups despite the use of different treatments. Despite
      clinical trials demonstrating the efficacy of many types of chemotherapy
      (cisplatin, etoposide, doxorubicin, dacarbazine), the value of adding these drugs
      to combination chemotherapy comprising of an alkylating agent (cyclophosphamide
      or ifosfamide), vincristine and dactinomycin has not been formally demonstrated
      in terms of survival benefit for children with rhabdomyosarcoma. The authors
      review these various results and compare the current guidelines for the
      management of orbital rhabdomyosarcoma recommended by North American and European
      groups.

PMID- 14640917
TI  - Merkel cell carcinoma--current therapeutic options.
AB  - Merkel cell carcinoma (MCC) is a rare, highly malignant skin tumour of
      neuroendocrine origin that occurs predominantly in elderly people in sun-exposed
      areas. It exhibits high levels of radiosensitivity and chemosensitivity both in
      vivo and in vitro. A variety of adverse prognostic factors have been identified
      which allow more aggressive therapy to be delivered to patients who are at higher
      risk of recurrence. The most powerful prognostic factor is the presence of nodal
      secondaries. Local disease should be excised, but there is some controversy over
      how wide the margins should be. Wide resection margins are not required provided
      postoperative radiotherapy is used. In the event of inoperable disease, patient
      refusal of surgery or frailty, radiotherapy can be used as the sole treatment
      modality, with a high likelihood of achieving local control. Patients with
      involved nodes have a higher risk of distant disease. Traditionally, involved
      nodes have been managed with resection but, currently, there are protocols
      exploring the use of synchronous chemoradiotherapy as definitive treatment.
      Although adjuvant chemotherapy has been used in this setting to reduce the risk
      of distant metastases, its role still remains under investigation. The presence
      of distant disease carries a grave outlook with responses to chemotherapy
      occurring frequently, albeit of short duration.

PMID- 14640918
TI  - Cyclooxygenase inhibition in cancer prevention and treatment.
AB  - Several lines of evidence suggest that the cyclooxygenase enzymes (specifically
      COX-2) might be an important molecular target for the intervention of cancer at
      both early and late stages of some cancers, providing an opportunity for both
      cancer prevention and therapy. COX-2 is overexpressed during carcinogenesis, and
      appears to have a role in both tumour initiation and promotion and is amenable to
      intervention. This review discusses the importance of COX modulation via non
      specific, as well as COX-2 specific COX inhibitors (NSAIDs and COX-2 selective
      inhibitors [COXIB]). A brief discussion on the pharmacoeconomic considerations of
      NSAID and COXIB use and safety issues that have recently been the focus of
      debate, will be presented.

PMID- 14640919
TI  - Systemic chemotherapy in the treatment of malignant melanoma.
AB  - Different postsurgical therapies are used for the treatment of metastatic
      melanoma. This article reviews the use of chemotherapeutic agents in the
      treatment of patients with metastatic malignant melanoma. A variety of single
      chemotherapy agents have been evaluated, although the most widely used
      chemotherapeutic in the treatment of metastatic melanoma is dacarbazine. In order
      to improve the rate and duration of responses, combination chemotherapy was
      developed. The most common combined chemotherapy regimens used as standard for
      the treatment of metastatic melanoma are Dartmouth regimen, CVD (cisplatin +
      vinblastine + dacarbazine) and BOLD (bleomycin + vincristine + lomustine +
      dacarbazine). However, Phase III trials have failed to demonstrate a significant
      benefit in survival in patients treated with polychemotherapy compared to those
      treated with dacarbazine alone. The use of classical systemic chemotherapy still
      has a role in the treatment of patients with metastatic melanoma. Immunotherapy
      and biochemotherapy have no additional advantage over chemotherapy.

PMID- 14640920
TI  - Anti-thrombotic therapy in cancer patients.
AB  - Primary and secondary prevention of venous thromboembolism (VTE) are the major
      roles of anti-thrombotic therapy in patients with cancer. Although the choices of
      pharmacological agents remain limited, low molecular weight heparins (LMWHs)
      offer important advantages over traditional anticoagulants. For prophylaxis in
      the surgical setting, once-daily subcutaneous injections of LMWH are as effective
      and safe as multiple doses of unfractionated heparin and extending prophylaxis
      with LMWH beyond hospitalisation can safely reduce the risk of postoperative
      thrombosis after abdominal surgery for cancer. For treatment and secondary
      prophylaxis, clinical trials have shown that LMWHs are feasible, safe and more
      effective than oral anticoagulants in preventing recurrent VTE in cancer
      patients. Nonetheless, formal economic analyses are needed to study the cost
      effectiveness of these agents. The preliminary observations that LMWHs are
      associated with reduction in cancer mortality make these agents an attractive
      therapeutic option in oncology patients.

PMID- 14640921
TI  - Pharmacotherapy of chemotherapy-induced anaemia.
AB  - Anaemia in cancer patients is multifactorial. Anaemia of chronic disease due to
      the effects of cancer, as well as side effects of cancer treatment, are important
      factors. The impact of anaemia on the quality of life and social function of
      cancer patients has recently become more acknowledged. The traditional treatment
      for chemotherapy-induced anaemia (CIA) has been the use of red blood cell
      transfusions, with only short-lived effects and all their inherent risks. The
      finding of deficiency in erythropoietin, the endogenous hormone responsible for
      the production and maintenance of red blood cells in these patients, was the
      basis for the therapeutic development of erythropoietic proteins. With the
      introduction of epoetins (recombinant forms of human erythropoietin) in oncology
      and more recently, the novel long-acting darbepoetin alpha, physicians gained new
      pharmacotherapeutic approaches to treat CIA. Several forms of erythropoietic
      proteins are available in various regions of the world. Their characteristics,
      clinical evidence for use, guidelines for clinical administration and their
      safety are described in this review.

PMID- 14640922
TI  - New developments in the pharmacotherapy of tension-type headaches.
AB  - The first International Headache Society classification defined tension-type
      headaches (TTHs) by itemising those characteristics of migraines TTHs did not
      possess [1]. As a result, TTHs, both episodic and chronic, remain the most
      nonspecific of all the commonly observed primary headaches. Until recently, there
      has been little impetus on the part of the pharmaceutical industry to investigate
      TTHs; many of the potentially useful drugs are now generic and unprofitable. In
      addition, few investigators have pursued the study of TTHs in lieu of its more
      glamorous neighbour, migraine. As a result, there are few well-designed studies
      on the pharmacotherapy of TTHs. The few studies that exist support the use of age
      old standard drug classes, the tricyclic antidepressants and the NSAIDs. New
      research is now emerging that points to the potential utility of botulinum toxin
      type A, NMDA-receptor antagonists including Mg(2+) and nitric oxide synthase
      inhibitors. More scientifically rigorous clinical studies are needed.

PMID- 14640923
TI  - Current and future therapy in haemochromatosis and Wilson's disease.
AB  - There have been several new developments in the treatment of iron and copper
      overload disorders, such as haemochromatosis, thalassaemia and Wilson's disease.
      Clinical trials of orally administered iron chelators, both as monotherapy and in
      combination with deferoxamine, are in progress around the world. Several new
      chelators are now being introduced in clinical trials. Future therapies for iron
      overload may comprise of oral iron binding agents capable of preventing dietary
      iron absorption from the diet. The characterisation of specific iron transporters
      such as the divalent metallic transporter and ferroportin may hold promise for
      the development of 'smart' compounds capable of blocking iron transport. Several
      new agents are now available for the management of Wilson's disease, including
      trientine, zinc and tetrathiomolybdate. This review, will discuss the
      pathogenesis, and current and future therapies for iron and copper overload
      disorders.

PMID- 14640924
TI  - Efficacy and safety of long-term bisphosphonates in postmenopausal osteoporosis.
AB  - Bisphosphonates have been in clinical use since the first approval of etidronate
      for myositis ossficans progressiva. They have now been used since the early 1990s
      for osteoporosis. As patients are continued on bisphosphonates and with
      consideration for bisphosphonate application in younger postmenopausal women,
      questions of 'how long to treat' are emerging in the clinical community. What is
      the evidence for continual efficacy and safety? The longest efficacy data where a
      placebo group was maintained is the 5-year risedronate vertebral fracture data,
      which demonstrated additional fracture reduction benefit with this bisphosphonate
      during years 4-5 of use. As bone mineral density (BMD) or biochemical markers of
      bone resorption (BCM) change very little for at least 1-2 years (and possibly
      longer) after discontinuing long-term (3-5 years) bisphosphonate use, it seems
      reasonable to suggest discontinuation for some indefinite period of time after 5
      years of use in younger lower-risk postmenopausal women. Monitoring of both BMD
      and BCM may indicate when to consider reinitiation of bisphosphonate therapy. In
      higher-risk elderly postmenopausal women who are doing well on long-term
      bisphosphonate therapy as defined by a stable BMD, height and no incident
      fractures, the same discussion of a 'honeymoon' period of no treatment could be
      entertained. However, because there are no data on fracture events post-treatment
      even without changing BMD or BCM, this author is reluctant to stop
      bisphosphonates in elderly high-risk patients. My opinion on the continuation of
      the use in high-risk patients is also predicated on the observations that there
      does not appear to be any clinically important safety issues with long-term (10
      year) use. Concerns about 'oversuppression' of bone turnover and accumulation of
      microdamage are theoretical and, so far, have no clinical basis for
      discontinuation in high-risk patients. It will be important, however, for the
      continual surveillance of bone safety issues by capturing postmarketing fracture
      data in patients on long-term therapy as well as long-term bone histomorphometry
      and measurements of bone quality to reassure clinicans about long-term
      bisphosphonate continuation.

PMID- 14640925
TI  - Sexual dysfunction with psychotropic drugs.
AB  - Sexual dysfunction caused by psychotropic medications has become an increasingly
      important clinical topic. Only recently have we acknowledged the extent to which
      many psychotropic medications, especially antidepressants and antipsychotics,
      cause sexual side effects. Prevalence rates of sexual side effects are
      extraordinarily difficult to estimate due to a variety of factors, such as the
      effect of the disorder being treated, comorbid disorders and baseline sexual
      dysfunction. Among the antidepressants, those with strong serotonergic properties
      have the highest rate of sexual side effects. Among the antipsychotics, those
      with greater D(2) blockade leading to increased prolactin levels are probably
      associated with more sexual dysfunction. Treatment approaches have been poorly
      developed for both antidepressants and antipsychotics. Antidotes for
      antidepressant-induced sexual dysfunction include bupropion, buspirone and
      sildenafil.

PMID- 14640926
TI  - Priapism--a review of the medical management.
AB  - Priapism is characterised by the presence of prolonged, often painful penile
      erection in the absence of a sexual stimulus. This rare condition has a range of
      aetiologies, but is most common following self-administration of injection
      therapy for impotence. Priapism may be classified into high- and low-flow states.
      Low-flow priapism is an emergency ischaemic condition requiring prompt
      recognition and treatment to avoid devastating long-term complications of
      erectile dysfunction. Wide-ranging medical therapies are covered in this review.
      Diagnostic and treatment algorithms are suggested in light of the current
      available literature.

PMID- 14640927
TI  - Aprepitant--a novel NK1-receptor antagonist.
AB  - Recently, a new class of agents, the substance P antagonists, has heralded a
      novel approach for the control of emesis. Aprepitant (Emend, Merck & Co., Inc.),
      the first of this class, was recently approved by the FDA for the prevention of
      both acute and delayed chemotherapy-induced nausea and vomiting (CINV). Of
      interest is the vast array of processes in which substance P is involved such as
      pain, anxiety, depression and inflammation and the potential wide applicability
      of substance P antagonists to a number of medical conditions outside of the
      nausea and vomiting realm. The following review provides an overview of
      aprepitant including pharmacokinetics, pharmacology and clinical evidence for its
      use in CINV. A brief discussion of other possible indications for aprepitant will
      also be presented.

PMID- 14640928
TI  - Palonosetron: a unique 5-HT3-receptor antagonist for the prevention of
      chemotherapy-induced emesis.
AB  - Palonosetron (Aloxi) is a 5-HT(3)-receptor antagonist antiemetic indicated for
      the prevention of acute and delayed nausea and vomiting following moderately
      emetogenic chemotherapy and for acute nausea and vomiting following highly
      emetogenic chemotherapy. Although it is the fourth member of this class to enter
      the US market, palonosetron is distinguished by distinct pharmacological
      characteristics. It has a higher binding affinity for the 5-HT(3 )receptor and a
      terminal serum half-life at least four times greater than any other available
      agent of this class (approximately 40 h). The high affinity and long half-life
      may explain the persistence of antiemetic effect throughout the delayed emesis
      risk period. The indications for palonosetron are supported by one dose-ranging
      study and three large, randomised, Phase III studies that all demonstrated at
      least equivalent activity (and in some cases, superior activity) compared to
      other 5-HT(3)-receptor antagonists. In spite of the pharmacological differences,
      the side effect profile of palonosetron is comparable to that of other 5-HT(3)
      receptor antagonists. Palonosetron may prove valuable in combination therapy for
      delayed emesis and may be an appropriate agent for clinical settings, such as
      multiple-day chemotherapy, where acute emesis is repeatedly induced. Palonosetron
      provides a convenience advantage if multiple-day 5-HT(3)-receptor antagonist
      therapy is anticipated and is a unique addition to the antiemetic armamentarium.

PMID- 14640929
TI  - Evaluation of memantine for the treatment of Alzheimer's disease.
AB  - Increasing evidence suggests that disturbances in glutamatergic activity play an
      important role in Alzheimer's disease (AD). Excessive glutamate-mediated
      activation of NMDA receptors, for example, may contribute to the neuronal death
      that characterises AD. On the other hand, physiological activation of the NMDA
      receptor appears necessary for normal cognitive function. Therefore, compounds
      that finely modulate NMDA receptor activity hold promise as treatments for AD.
      Memantine (Namenda, Axura, Ebixa; Forest Laboratories, Inc., Merz Pharmaceuticals
      GmbH, H. Lundbeck A/S) is a low-moderate affinity, uncompetitive NMDA-receptor
      antagonist that appears to block pathological, but not physiological, activation
      of the NMDA receptor. Consequently, therapeutic doses of the drug are well
      tolerated and do not seem to interfere with the acquisition or processing of
      cognitive information. Memantine has been shown to improve symptoms and reduce
      the rate of clinical deterioration among patients with moderate-to-severe AD and
      was approved in the US for this indication in October 2003. This review provides
      a brief rationale for the development of memantine as a therapy for AD, as well
      as an overview of the pharmacology, clinical efficacy, safety and tolerability of
      this novel therapeutic agent.

PMID- 14640930
TI  - Transdermal oxybutynin: a new treatment for overactive bladder.
AB  - Overactive bladder has been successfully treated with oral anticholinergic drugs
      such as oxybutynin chloride. Although oral oxybutynin has been effective in
      controlling urinary urge incontinence and in decreasing incontinence episodes,
      adverse events, particularly dry mouth, often cause patients to discontinue oral
      therapy and to endure incontinence. Transdermal oxybutynin (Oxytrol, Watson
      Pharmaceuticals) is applied twice-weekly to maintain the efficacy of oral
      oxybutynin while significantly minimising side effects (e.g., dry mouth) that
      complicate therapy. By avoiding hepatic and gastrointestinal metabolism of
      oxybutynin, less N-desethyloxybutynin (N-DEO), the compound thought to be
      responsible for anticholinergic side effects, such as dry mouth, is produced. The
      new transdermal oxybutynin formulation offers patients with urinary incontinence
      an effective, safe and well-tolerated option for managing the symptoms of
      overactive bladder.

PMID- 14640931
TI  - Mycophenolate mofetil in solid-organ transplantation.
AB  - This review focuses on the use of mycophenolate mofetil (MMF) as an
      immunosuppressive agent in solid-organ transplantation. MMF, a non-competitive
      inhibitor of inosine monophosphate dehydrogenase, blocks de novo purine synthesis
      in T and B lymphocytes, resulting in the selective inhibition of proliferation of
      these cells in response to antigenic stimuli. MMF may also promote apoptosis of
      these cells. The immunosuppressive ability of MMF is thought to derive mainly
      from the inhibition of inosine monophosphate dehydrogenase. The other effects of
      MMF include suppression of antibody synthesis by B lymphocytes, inhibition of
      proliferation of smooth muscle cells in culture and impaired glycosylation of
      adhesion molecules. MMF may exhibit anti-inflammatory effects resulting from
      decreased activity of the inducible form of nitric oxide synthase, a consequence
      of depletion of tetrahydrobiopterin, which leads to decreased generation of
      peroxynitrite, a pro-inflammatory molecule. The pharmacokinetics,
      pharmacodynamics and principles underlying therapeutic drug monitoring of MMF are
      reviewed. The results of the pivotal clinical trials of MMF in kidney and heart
      transplantation are discussed and a summary of the major studies demonstrating a
      positive effect of MMF on renal transplantation outcomes is presented. The use of
      MMF in the context of ABO-incompatible renal transplantation, renal
      transplantation in highly sensitised and cross-match positive recipients, humoral
      rejection of renal allografts, chronic allograft nephropathy and
      steroid/calcineurin inhibitor minimisation in renal transplantation are also
      discussed.

PMID- 14640932
TI  - The efficacy of topical tazarotene monotherapy and combination therapies in
      psoriasis.
AB  - Tazarotene (Tazorac, Allergan, Inc.) is the first topical retinoid approved for
      the treatment of plaque psoriasis. It has a similar onset of action compared to
      potent topical steroids and has the advantage of a longer remission. The common
      side effects associated with the drug include skin irritation (including
      pruritus), erythema and a burning sensation. To overcome some of these
      shortcomings, it has been used in combination with steroids, calcipotriene and
      phototherapy. Combination therapy not only results in a decrease in adverse side
      effects, but also enhanced efficacy. Clinical study data have shown that
      combination therapy is just as important as tazarotene monotherapy, if not more.

PMID- 14640933
TI  - Tinzaparin in the treatment of venous thromboembolism.
AB  - Low molecular weight heparin (LMWH) has been widely used for the initial
      treatment of patients presenting with venous thromboembolism. The LMWH,
      tinzaparin, has been shown in randomised clinical trials to be as effective and
      safe as unfractionated heparin for the initial treatment of venous
      thromboembolism and in clinical trials, it has been used in place of warfarin for
      the long-term treatment of deep vein thrombosis. Tinzaparin can safely be given
      to patients with significant renal impairment (creatinine clearance of > or = 20
      ml/min) and the dose of tinzaparin does not need to be altered in patients with a
      body mass index of > 25.

PMID- 14640934
TI  - Recurrent hope for the treatment of preterm delivery.
AB  - Preterm delivery is the major determinant of infant mortality and there is a lack
      of treatments for this condition. Women presenting for prenatal care with a
      history of a spontaneous preterm delivery were assigned 17 alpha-progesterone
      caproate (17P) 250 mg/week i.m. between 16 and 20 weeks of gestation or placebo
      until 36 weeks of gestation or delivery, whichever came first. The primary
      outcome was preterm delivery before 37 weeks of gestation and this occurred less
      often in the 17P group than in the placebo group (36.3 versus 54.9%,
      respectively; p < 0.001). Among the infants, there was a reduction in the risk of
      a birth weight of < 2500 g in the 17P compared to the placebo group (27.2 versus
      41%, respectively). As a result of this clinical trial, 17P should be routinely
      used as a preventative in women with a history of spontaneous preterm delivery.

PMID- 14640935
TI  - IACM 2nd Conference on Cannabinoids in Medicine.
AB  - The International Association for Cannabis as Medicine 2nd Conference on
      Cannabinoids in Medicine focused on new clinical research with cannabis and
      single cannabinoids (Delta(9)-tetrahydrocannabinol, CT-3) and on animal research
      with possible therapeutic implications. The meeting brought together basic
      researchers, clinicians and physicians to facilitate an exchange of knowledge and
      experience in this field. Even a talk by a patient with multiple sclerosis was
      included in a workshop on neurology. Current clinical research with cannabinoids
      focuses mainly on chronic pain and neurological disorders adding to accepted
      indications such as anorexia in AIDS-wasting and antiemetic effects in cancer
      chemotherapy. First results are promising and larger studies are underway or have
      recently been completed and are awaiting publication. New basic research opens
      further areas of possible uses for modulators of the endogenous cannabinoid
      system, including osteoporosis, cancer and inflammation. A workshop on psychiatry
      focused on effects of cannabis use on onset, incidence and the course of
      schizophrenia. Basic and clinical research shows that adolescents might be more
      vulnerable than adults to possible psychiatric effects of cannabinoids. It was
      concluded that possible side effects of cannabinoids should be taken into account
      but do not preclude a legitimate medical use.

PMID- 14640936
TI  - Novel chemotherapeutic agents for the treatment of glioblastoma multiforme.
AB  - During the last few decades, the discovery of novel targets for therapeutic
      intervention led to the development of chemotherapeutic agents that specifically
      interfere with altered cellular functions of tumour cells. Genetic alterations in
      glioblastoma affect cell proliferation and cell cycle control, as well as
      invasive and metastatic growth. Therefore, innovative therapeutic strategies have
      been based on drugs targeting cellular proliferation, invasion, angiogenesis,
      metastasis and differentiation of tumour cells. Furthermore, disruption of cell
      death pathways also contributes to the pathogenesis of glioblastoma and may
      result in resistance to chemotherapy and radiation. Therefore, additional
      treatment strategies that target intracellular survival and/or apoptotic pathways
      are under current laboratory investigation. The progress in the understanding of
      glioblastoma tumour biology and the refined diagnosis of individual patients
      together with the exploration of targeted drugs may allow a risk-adapted,
      individualised therapeutic strategy and will hopefully improve prognosis of
      glioblastoma patients in the future.

PMID- 14640937
TI  - Therapeutic potential of thiazolidinediones as anticancer agents.
AB  - Thiazolidinediones (TZDs) are synthetic ligands that activate the nuclear
      receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These
      compounds are widely used in the treatment of Type 2 diabetes. TZDs have
      antitumour activity in a wide variety of experimental cancer models, in vitro and
      in vivo, by affecting the cell cycle, induction of cell differentiation and
      apoptosis as well as by inhibiting tumour angiogenesis. These effects are
      mediated through both PPAR-gamma-dependent and -independent pathways depending on
      concentration and tumour cell type. Angiogenesis inhibition mechanisms of TZDs
      include directly inhibiting endothelial cell proliferation and migration as well
      as decreasing tumour cell vascular endothelial growth factor production. Further
      studies suggest that TZDs may be effective in prevention of certain cancers and
      in the treatment of cancer as adjuvant therapy.

PMID- 14640938
TI  - Novel chemotherapeutic and targeted agents in metastatic colorectal cancer: the
      time has arrived.
AB  - Colorectal cancer is a common disease with a high rate of mortality and very well
      understood genetics. Primary therapy still consists of relatively non-specific
      treatments: surgery, radiotherapy and chemotherapy. In this article, recent data
      in the now fast-moving field of treatment of unresectable metastatic colorectal
      cancer are reviewed, beginning with new developments in conventional cytotoxic
      therapies. A number of new cytotoxic agents appear to have at least some activity
      in this disease, including classes of drugs that have been effective to date. The
      very rapidly growing area of targeted therapy will also be expanded upon. This
      year, for the first time, there has been a targeted therapy shown convincingly to
      prolong survival for patients with unresectable metastatic colorectal cancer in a
      well-performed Phase III trial. This agent is bevacizumab, a humanised monoclonal
      antibody targeting the circulating proangiogenic growth factor vascular
      endothelial growth factor. Results with bevacizumab should lead to rapid
      expansion of the number of strategies targeting tumour neovasculature.
      Additionally, an antibody against the epidermal growth factor, cetuximab, has
      been shown to have both single-agent activity and the potential ability to
      partially reverse resistance to a chemotherapy drug. These advancements, as well
      as data on other novel treatment agents that have been studied specifically in
      patients with colorectal neoplasms, are discussed in detail.

PMID- 14640939
TI  - Novel FLT3 tyrosine kinase inhibitors.
AB  - Acute myeloid leukaemia (AML) is an aggressive haematological malignancy that is
      curable in approximately 40% of cases. Activating mutations of the receptor
      tyrosine kinase FLT3 (FMS-like tyrosine kinase-3) are the single most common
      molecular abnormalities in AML and are associated with a distinctly worse
      prognosis. In an effort to target this mutation and improve outcomes in this
      subgroup of AML patients, several novel small-molecule FLT3 tyrosine kinase
      inhibitors are currently in development. Some of these FLT3 inhibitors are useful
      only as laboratory tools, while others clearly have clinical potential. These
      compounds are derived from a wide variety of chemical classes and differ
      significantly both in their potency and selectivity. This review summarises these
      developments and examines these novel agents with regard to both the assays used
      to characterise them and their clinical potential.

PMID- 14640940
TI  - The role of mineralocorticoid receptor antagonists in the treatment of cardiac
      failure.
AB  - In most countries the last two decades have seen a very substantial rise in the
      prevalence of heart failure, and in a majority of patients hypertension is both
      an antecedent condition and a contributing cause. Heart failure is also a major
      cause of hospital admissions; its amelioration and, as far as possible,
      prevention is therefore important in terms not only of morbidity and premature
      mortality for the individual patient, but also containment of healthcare costs.
      Over the past 5 years, mineralocorticoid receptor (MR) antagonists have been used
      in two major outcome trials (the Randomized Aldactone Evaluation Study [RALES]
      with spironolactone, and the Eplerenone Post-AMI Heart Failure Efficacy and
      Survival Study [EPHESUS]), in severe (New York Heart Association class III) and
      post-myocardial infarct heart failure, respectively. Experimental studies have
      largely focused, however, on various animal models of hypertension; on the basis
      of a portfolio of clinical studies on the efficacy of eplerenone, administered
      either alone and in combination as an antihypertensive agent, the novel MR
      antagonist was approved by the FDA for the treatment of hypertension, though it
      has yet to be launched. In this review, the two major outcome studies (RALES,
      EPHESUS) are discussed in the context of the new biology of aldosterone action.
      The relevance to heart failure of current experimental studies, largely on
      vascular protection, will also be discussed.

PMID- 14640941
TI  - Update on acute coronary syndromes and implications for therapy.
AB  - Our understanding of the pathophysiology of acute coronary syndromes (ACS),
      including acute ST elevation myocardial infarction, unstable angina and non-ST
      segment elevation (NSTE) myocardial infarction, has evolved considerably over the
      years, with atherothrombosis playing a pivotal role. This review will discuss the
      recent advances/recommendations for drug therapy based on this enhanced
      understanding of the pathophysiology of thrombosis. More recently developed
      agents, such as low-molecular-weight heparins (LMWHs), glycoprotein (GP) IIb-IIIa
      inhibitors, direct thrombin inhibitors, Factor Xa inhibitors and thienopyridines,
      offer several potential advantages, either as an alternative to unfractionated
      heparin (i.e., LMWHs) or as an add-on therapy to aspirin and unfractionated
      heparin (or LMWHs; e.g., GP IIb-IIIa inhibitors, thienopyridines). The purpose of
      this review is to describe recent studies with novel antithrombotic agents (e.g.,
      LMWHs, thienopyridines, GP IIb-IIIa inhibitors, bivalirudin) in patients with
      NSTE ACS, as well as to highlight recommendations for management of patients with
      NSTE ACS in the recently updated American College of Cardiology (ACC)/American
      Heart Association (AHA) guidelines, including the appropriate use of
      antithrombotic therapies.

PMID- 14640942
TI  - DNA methylation in haematological malignancies: the role of decitabine.
AB  - Normal cell development and function is dependent upon controlled gene
      expression. DNA methylation is an epigenetic modification that can play an
      important role in the control of gene expression. DNA methylation at cytosine
      residues in gene promoter CpG sequences is known to inhibit gene transcription.
      Inappropriate inhibition of the transcription of tumour suppressor genes, genes
      that inhibit angiogenesis and metastasis and genes involved in DNA repair by
      uncontrolled methylation, can lead to unregulated growth and proliferation of a
      cell and carcinogenesis. Promoter hypermethylation affecting the p16 gene,
      resulting in gene silencing, has been shown to occur in many human solid tumours
      and a 'hypermethylation profile' in some leukaemias has been defined. The
      molecular mechanisms by which aberrant DNA methylation takes place during
      carcinogenesis are still not clear. However, the large number of target genes
      (involved in tumorigenesis) that are silenced by aberrant methylation suggests
      that inhibition of this process may have potential as cancer therapy. Decitabine
      (NSC-127716, Dacogen; SuperGen) is a potent and specific hypomethylating agent
      and an inhibitor of the DNA methyltransferase activity that mediates DNA
      methylation. Decitabine has been shown to have a broad range of antineoplastic
      activity in preclinical studies. This agent has exhibited significant activity in
      the treatment of patients with myelodysplastic syndrome, chronic myeloid
      leukaemia and acute myeloid leukaemia, although clinical Phase I and II studies
      with solid tumours have not been very promising. Phase II and III studies are
      currently ongoing to evaluate decitabine, both alone and in combination, in
      various stages of these haematological malignancies.

PMID- 14640943
TI  - 13th European Respiratory Society Annual congress.

PMID- 14640944
TI  - Angiogenesis: new opportunities and solutions for drug development. Predictive
      markers for antiangiogenic drugs.

PMID- 14640945
TI  - Bacterial biofilms of importance to medicine and bioterrorism: proteomic
      techniques to identify novel vaccine components and drug targets.
AB  - Biofilms are highly ordered microbial communities enmeshed in a carefully
      sculpted matrix designed for survival of organisms either in multi- or mono
      genus/species in a specific microniche. In human disease, biofilm infections are
      some of the most recalcitrant to treat. Even with rigorous antibiotic regimens,
      some biofilms, such as those within the thick airway mucus of cystic fibrosis
      (CF) patients, persist throughout the course of the disease process. In this
      editorial, discussion will cover the utility of using advanced proteomic
      techniques to help identify potential weaknesses in the already impressive
      defensive armamentarium of biofilm bacteria. Two biofilm systems will be
      discussed herein, one of which is that of Pseudomonas aeruginosa biofilms within
      CF airway biofilms. The other is referred to as persistent 'bioterrorist agent
      biofilms' in which Francisella tularensis can grow on surfaces where
      environmental amoeba can phagocytose them, allowing for growth of F. tularensis
      within the amoebae.

PMID- 14640946
TI  - Biologic strategies for the therapy of intervertebral disc degeneration.
AB  - Recent advances in tissue engineering have led to promising new approaches for
      the biologic treatment of disc degeneration. At present, there is no effective
      therapy for disc degeneration, a condition which results in large healthcare and
      socio-economic costs. This article will examine the current approaches used in
      biologic therapies for disc degeneration, including cell-based tissue
      engineering, gene therapy and the application of mesenchymal stem cells, and
      discuss their therapeutic potential, as demonstrated in animal models and
      experimental studies to date.

PMID- 14640947
TI  - Haematopoietic cell transplantation in the treatment of sickle cell disease.
AB  - Allogeneic haematopoietic cell transplantation (HCT) is presently the only
      treatment which offers the possibility of a cure for patients with sickle cell
      disease (SCD). While approximately 84% of patients survive disease-free after
      human leukocyte antigen (HLA)-identical sibling donor HCT, this therapy has
      traditionally been reserved for patients who have suffered serious complications
      due to the risk of transplant-related morbidity and mortality. Typically, these
      sickle-related complications have included recurrent episodes of acute chest
      syndrome, recurrent vaso-occlusive episodes and stroke. The future of HCT for
      haemoglobinopathies undoubtedly will evolve as transplant-related complications
      are reduced and as the process of selecting patients for HCT is refined.

PMID- 14640948
TI  - The role of biological response modifiers in malignant melanoma.
AB  - This article reviews the existing data in an attempt to address the role of
      biological response modifiers (IFN-alpha and IL-2) in the management of melanoma.
      Eight prospective controlled Phase III trials evaluating IFN-alpha therapy are
      discussed. As the results from these trials have been heterogeneous and
      inconsistent, the role of IFN-alpha in the adjuvant treatment of stage II and III
      melanoma patients remains to be defined. IL-2 possesses modest antitumour
      activity in melanoma yielding objective response in approximately 15% of
      patients. Many toxic effects are induced by high-dose IL-2 therapy. Combinations
      of chemotherapy and biological response modifiers and their impact on tumour
      response and survival are discussed.

PMID- 14640949
TI  - Exploiting the neurotherapeutic potential of peptides: targeted delivery using
      HSV vectors.
AB  - Neurotrophic factors and peptide neurotransmitters represent two classes of
      potent macromolecules whose therapeutic use in the treatment of neurologic
      disease is limited by unwanted effects that result from the widespread
      distribution of cognate receptors within and beyond the neuraxis. Targeted gene
      delivery to sensory neurons of the dorsal root ganglion (DRG) by subcutaneous
      inoculation of herpes simplex virus (HSV)-based gene transfer vectors may be used
      to achieve local expression and release of these pleiotropic, short-lived
      molecules in a restricted area. Recent studies demonstrate that HSV-mediated
      transfer of genes coding for neurotrophic factors prevents the progression of
      disease in animal models of drug-induced or diabetic polyneuropathy and that HSV
      mediated transfer of genes coding for inhibitory neurotransmitters provides a
      regional analgesic effect in animal models of chronic pain. The first human trial
      of HSV-mediated gene transfer to DRG is about to commence. HSV-mediated gene
      transfer may allow the therapeutic potential of these peptides for the treatment
      of neurologic disease to be realised.

PMID- 14640950
TI  - Prospects and RISC score of viral gene therapy for sarcoma.
AB  - Soft tissue sarcomas are a challenge for medical oncology and gene therapy.
      Protective and sensitising approaches that target normal and malignant tissue,
      respectively, both have their role for opening the therapeutic window. Recent
      data show that an intensive maintenance chemotherapy significantly reduces
      metastatic spread and improves disease-free survival in selected patient groups.
      However, delays of treatment due to cytopenia are frequent. Cytostatic drug
      resistance gene transfer to haematopoietic progenitor cells using retroviral
      vectors may allow further improvement of therapy results. In recent years,
      retroviral vector design, transduction techniques and engraftment capability of
      transduced cells have been optimised. Safety considerations of retroviral gene
      transfer have attracted public attention and can be addressed by analysis of
      genomic vector integration sites. A data bank project, 'retroviral insertion
      estimate of chromosomal integration' (RISC), containing > 200 integration
      sequences, has been set up by the authors' group to recognise critical genomic
      regions and genes involved with possible transforming capacity. Monitoring these
      parameters will allow the selection of the most suitable vectors for clinical
      application. Sarcoma cells seem to be highly susceptible to a variety of vectors,
      such as recombinant adeno-associated virus-2 (rAAV-2) vectors, adenoviral vectors
      or oncolytic herpes simplex viruses. Results from the first clinical trials with
      adenoviral vectors encoding for cytokines are promising. The other systems await
      further development towards clinical applications. Perspectives for further
      research are discussed in this review.

PMID- 14640951
TI  - Chemical and biological properties of polymer-modified proteins.
AB  - Modification with polymers such as polyethylene glycol (PEG) can increase
      circulating lifetime, reduce immunogenicity and simplify the handling of
      pharmaceutical proteins. These benefits are currently exploited in six marketed
      polymer-modified protein therapeutics and about a dozen product candidates in
      clinical trials. However, traditional protein modification techniques are
      restricted by the limited control over polymer structure and the location and
      number of polymer attachment sites. New technology, in the form of chemical
      protein synthesis and the generation of precision polymers, has been applied to
      generate synthetic erythropoiesis protein (SEP). This promising treatment for
      anaemia has been synthesised with precision polymer modification methodology to
      improve the target protein pharmaceutical. The chemical and biological properties
      of proteins prepared by both traditional and novel approaches are contrasted in
      this discussion of chemical protein synthesis and polymer modification in protein
      drug discovery.

PMID- 14640952
TI  - Bacterial spores as heat stable vaccine vehicles.
AB  - Recently, the first use of bacterial spores as vaccine vehicles was reported,
      showing that mice orally immunised with Bacillus subtilis spores expressing a
      tetanus antigen could be protected against lethal challenge with tetanus toxin.
      Unlike many second generation vaccine systems currently under development, none
      offer the heat stability of bacterial spores or the flexibility for genetic
      manipulation. The current use of Bacillus spores as probiotics for both humans
      and animals may facilitate their eventual licensing as oral vaccines. This review
      reports the progress that has been made in the establishment of bacterial spores
      as vaccine vehicles and outlines the potential advantages of the spore vaccine
      approach.

PMID- 14640953
TI  - Schistosomiasis vaccines.
AB  - While there are many challenges in vaccine development, none is greater than that
      of developing vaccines against large metazoan parasites such as schistosomes, the
      parasitic worms that are responsible for schistosomiasis. Initial optimism
      stemming from the identification of the first vaccine candidate antigens that
      gave protection in animals has been dashed by the failure, as yet, of any of the
      vaccine candidate antigens to enter Phase III clinical trials. Now, despite an
      improved understanding of the biology of the parasites and of the immune
      responses they stimulate in naturally exposed populations, the vaccine effort is
      stalled. The control effort has switched heavily in favour of the wider use of
      conventional chemotherapy with praziquantel, which is now affordable by all but
      the poorest countries. Disagreements among researchers in the schistosome field
      as to whether or not a vaccine is needed have not helped convince funding
      agencies that schistosomiasis vaccines, rather than drugs, should be a priority.
      With the schistosome genome projects at an advanced stage plus the power of the
      proteomics, perhaps it is still too early to call time on schistosome vaccine
      development.

PMID- 14640954
TI  - Defensive applications of gene transfer technology in the face of bioterrorism:
      DNA-based vaccines and immune targeting.
AB  - Gene transfer involves the introduction of an engineered gene into a person's
      cells with the expectation that the protein expressed from the gene will produce
      a therapeutic benefit. Strategies based on this principle have led to the
      approval of > 600 clinical trials and enrollment of approximately 3500 subjects
      worldwide in attempts to treat diseases ranging from cancer to AIDS to cystic
      fibrosis. While gene therapy has met with limited success and still has many
      hurdles to overcome before it sees wide application, it may be useful as a
      defensive strategy against bioterrorism agents including infectious microbes and
      toxins. Although many defensive strategies are possible, immunological strategies
      are currently the most developed and are being actively applied to the
      development of strategies against several of the most virulent potential bio
      weapons. While most of these strategies are not yet ready for human application,
      DNA-based vaccines appear to be among the most promising in the fight against
      bioterrorism.

PMID- 14640955
TI  - 6th World Congress on Inflammation.
AB  - The 6th World Congress on Inflammation was held in the Vancouver Convention and
      Exhibition Center. This biennial meeting was organised by the Inflammation
      Research Association (USA) and Triangle 3 Ltd (UK), under the auspices of the
      International Association of Inflammation Societies. This meeting aimed to
      promote international cooperation amongst inflammation scientists and provide a
      communication network for various inflammation societies from around the world.
      The conference covered the most up-to-date concepts in inflammation, new drugs
      and treatments, and advances in cell biology. However, there were some topics
      which were either novel to many attendees or which provided links to a number of
      presentations, thus underlining their importance. The following is by no means an
      exhaustive review, but merely reflects the authors' interests.

PMID- 14640956
TI  - World conference on lung cancer.
AB  - Lung cancer is the most frequent cause of cancer death. Improving this dismal
      outcome requires cooperation among several specialists. The 10th World Conference
      on Lung Cancer was held in Vancouver, Canada last month. The meeting was
      organised on behalf of the International Association for the Study of Lung Cancer
      (IASLC) and the British Columbia Cancer Agency. This Conference was chaired by
      Nevin Murray and the scientific sessions took place 10 - 14 August, with > 3000
      participating lung cancer experts. The Vancouver programme included > 140 invited
      speakers throughout the 'meet the professor', plenary and interactive sessions,
      as well as 300 oral and 500 poster presentations.

PMID- 14640957
TI  - Structural and functional features of formate hydrogen lyase, an enzyme of mixed
      acid fermentation from Escherichia coli.
AB  - Formate hydrogen lyase from Escherichia coli is a membrane-bound complex that
      oxidizes formic acid to carbon dioxide and molecular hydrogen. Under anaerobic
      growth conditions and fermentation of sugars (glucose), it exists in two forms.
      One form is constituted by formate dehydrogenase H and hydrogenase 3, and the
      other one is the same formate dehydrogenase and hydrogenase 4; the presence of
      small protein subunits, carriers of electrons, is also probable. Other proteins
      may also be involved in formation of the enzyme complex, which requires the
      presence of metal (nickel-cobalt). Its formation also depends on the external pH
      and the presence of formate. Activity of both forms requires F(0)F(1)-ATPase;
      this explains dependence of the complex functioning on proton-motive force. It is
      also possible that the formate hydrogen lyase complex will exhibit its own proton
      translocating function.

PMID- 14640958
TI  - Non-apoptotic functions of caspase-3 in nervous tissue.
AB  - Some enzymes that have been recognized as "apoptotic" so far may be involved in
      important cellular processes not necessarily related to cell death in nervous
      tissue. The activity of caspase-3, an "apoptotic" enzyme, can be measured in
      normally functioning neurons. The results reported by several groups point to the
      possibility that caspases may be involved in nervous tissue function as top
      enzymes in the regulatory proteolytic cascade. A concept on a new mechanism of
      synaptic plasticity modulation involving caspase-3 has been formulated
      postulating a specific role of caspase-3 in normal brain functioning. The idea of
      synaptic plasticity modulation by caspase-3 is in line with data reported
      recently. For example, caspase-3 is possibly involved in the long-term
      potentiation (LTP) phenomenon since proteins that are key players of molecular
      mechanisms of LTP induction and maintenance are caspase-3 substrates.
      Experimental results on blocking LTP by a caspase-3 inhibitor confirm this
      concept.

PMID- 14640959
TI  - Role of arginine 226 in the mechanism of tryptophan indole-lyase from Proteus
      vulgaris.
AB  - In the spatial structure of tryptophanase from Proteus vulgaris the guanidinium
      group of arginine 226 forms a salt bridge with the 3;-oxygen atom of the
      coenzyme. The replacement of arginine 226 with alanine using site-directed
      mutagenesis reduced the affinity of the coenzyme for the protein by one order of
      magnitude compared to the wild-type enzyme. The catalytic activity of the mutant
      enzyme in the reaction with L-tryptophan was reduced 10(5)-fold compared to the
      wild-type enzyme. The rates of the reactions with some other substrates decreased
      10(3)-10(4)-fold. The mutant enzyme catalyzed exchange of the C-alpha-proton in
      complexes with some inhibitors with rates reduced 10(2)-fold compared to the wild
      type enzyme. Absorption and circular dichroism spectra of the mutant enzyme and
      the enzyme-inhibitor complexes demonstrate that the replacement of arginine 226
      with alanine does not significantly affect the tautomeric equilibrium of the
      internal aldimine, but it leads to an alteration of the optimal conformation of
      the coenzyme-substrate intermediates.

PMID- 14640960
TI  - Expression and refolding of tobacco anionic peroxidase from E. coli inclusion
      bodies.
AB  - Coding DNA of the tobacco anionic peroxidase gene was cloned in pET40b vector.
      The problem of 11 arginine codons, rare in procaryotes, in the tobacco peroxidase
      gene was solved using E. coli BL21(DE3) Codon Plus strain. The expression level
      of the tobacco apo-peroxidase in the above strain was approximately 40% of the
      total E. coli protein. The tobacco peroxidase refolding was optimized based on
      the earlier developed protocol for horseradish peroxidase. The reactivation yield
      of recombinant tobacco enzyme was about 7% with the specific activity of 1100
      1200 U/mg towards 2,2;-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS). It
      was shown that the reaction of ABTS oxidation by hydrogen peroxide catalyzed by
      recombinant tobacco peroxidase proceeds via the ping-pong kinetic mechanism as
      for the native enzyme. In the presence of calcium ions, the recombinant
      peroxidase exhibits a 2.5-fold decrease in the second order rate constant for
      hydrogen peroxide and 1.5-fold decrease for ABTS. Thus, calcium ions have an
      inhibitory effect on the recombinant enzyme like that observed earlier for the
      native tobacco peroxidase. The data demonstrate that the oligosaccharide part of
      the enzyme has no effect on the kinetic properties and calcium inhibition of
      tobacco peroxidase.

PMID- 14640961
TI  - Active dimeric form of inorganic pyrophosphatase from Escherichia coli.
AB  - A dimeric form can be obtained from native hexameric Escherichia coli inorganic
      pyrophosphatase (E-PPase) by destroying the hydrophobic intersubunit contacts,
      and it has been shown earlier to consist of the subunits of different trimers.
      The present paper is devoted to the kinetic characterization of such a "double
      decked" dimer obtained by the dissociation of either the native enzyme or the
      mutant variant Glu145Gln. The dimeric form of the native inorganic
      pyrophosphatase was shown to retain high catalytic efficiency that is in sharp
      contrast to the dimers obtained as a result of the mutations at the intertrimeric
      interface. The dimeric enzymes described in the present paper, however, have lost
      the regulatory properties, in contrast to the hexameric and trimeric forms of the
      enzyme.

PMID- 14640962
TI  - Isolation and properties of major components of Penicillium canescens
      extracellular enzyme complex.
AB  - The composition of the enzyme complex secreted by Penicillium canescens was
      investigated. A scheme for purification of the main components of the complex by
      chromatofocusing on a Mono P column was developed. It was found that along with
      beta-galactosidase, the major components of the complex were endo-beta-1,4
      xylanase (31 kD, pI 8.2-9.3), alpha-L-arabinofuranosidase (60 kD, pI 7.6),
      arabinoxylan-arabinofuranohydrolase (70 kD, pI 3.8-4.0), and endo-beta-1,3/1,4
      glucanase (40 kD, pI 4.4). The substrate specificity, pH and temperature activity
      optima, adsorbability, thermal stability, and ability for synergic interaction of
      the isolated enzymes were studied.

PMID- 14640963
TI  - H2O2-induced platelet aggregation and increase in intracellular Ca2+
      concentration are blocked by inhibitors of intracellular signaling.
AB  - Inhibitors of signaling enzymes such as guanosine-5;-O-2-thiodiphosphate,
      aristolochic acid, aspirin, indomethacin, and trifluoperazine block H2O2-induced
      platelet aggregation and H2O2-induced increase in the intracellular concentration
      of Ca2+. These findings suggest that the effect of H2O2 on platelets is
      associated with activation of signal pathways responsible for increase in the
      concentration of intracellular Ca2+. On H2O2-induced platelet aggregation, the
      concentration of cAMP in the cytoplasm decreases and that of cGMP increases.

PMID- 14640964
TI  - Isolation and characterization of glutamyl endopeptidase 2 from Bacillus
      intermedius 3-19.
AB  - The culture filtrate of Bacillus intermedius 3-19 was used for isolation by
      chromatography on CM-cellulose and Mono S columns of a proteinase that is
      secreted during the late stages of growth. The enzyme is irreversibly inhibited
      by the inhibitor of serine proteinases diisopropyl fluorophosphate, has two pH
      optima (7.2 and 9.5) for casein hydrolysis and one at pH 8.5 for Z-Glu-pNA
      hydrolysis. The molecular weight of the enzyme is 26.5 kD. The K(m) for Z-Glu-pNA
      hydrolysis is 0.5 mM. The temperature and pH dependences of the stability of the
      proteinase were studied. The enzyme was identified as glutamyl endopeptidase 2.
      The N-terminal sequence (10 residues) and amino acid composition of the enzyme
      were determined. The enzyme hydrolyzes Glu4-Gln5, Glu17-Asp18, and Cys11-Ser12
      bonds in the oxidized A-chain of insulin and Glu13-Ala14, Glu21-Arg22, Cys7-Gly8,
      and Cys19-Gly20 bonds in the oxidized B-chain of insulin.

PMID- 14640965
TI  - Conformational differences between native and recombinant horseradish peroxidase
      revealed by tritium planigraphy.
AB  - Significant conformational differences between native and recombinant horseradish
      peroxidase have been shown by tritium planigraphy, which includes a method of
      thermal activation of tritium followed by amino acid analysis of the protein
      preparation. Comparison of radioactivity distribution among the amino acid
      residues with the theoretical (calculated) accessibility shows that the
      recombinant enzyme is characterized by high hydrophobicity and compactness of
      folding. The protective role of oligosaccharides in native enzyme has been
      confirmed. An unexpected result of the study is a finding on high accessibility
      of a catalytic histidine residue in solution. An effect of low dose (3 Gy) of
      irradiation on the accessibility of amino acid residues has been unequivocally
      demonstrated. The data can be interpreted as swelling of the compact folding and
      increase in the surface hydrophilicity of the recombinant enzyme. In the case of
      native enzyme, irradiation does not cause remarkable changes in the accessibility
      of amino acid residues indicating the possible extensive radical modification of
      the native enzyme in the life-course of the cell. The catalytic histidine is an
      exception. It becomes inaccessible after the enzyme irradiation, while its
      accessibility in the recombinant enzyme increases. An additional observation of a
      5-fold decrease in the rate constant towards hydrogen peroxide points to the
      destructive effect of irradiation on the hydrogen bond network in the distal
      domain of the native enzyme molecule and partial collapse of the active site
      pocket.

PMID- 14640966
TI  - Properties of antigenomic hepatitis delta virus ribozyme that consists of three
      RNA oligomer strands.
AB  - A three-strand ribozyme, a derivative of antigenomic hepatitis delta virus (HDV)
      ribozyme, which consists of subfragments of 16 (L), 17 (S), and 33 nucleotides
      (B), has been constructed. The ternary B-L-S complex formed by the subfragments
      in stoichiometric ratio was able to catalyze a self-cleavage reaction. Kinetics
      of this reaction exhibited biphasic behavior and the same parameters as in the
      case of natural cis-ribozyme. Study of kinetics of reaction initiated by adding
      various reaction components and the study of binary complex formation between
      subfragments B and L, B and S, and also ternary B-L-S complex formation revealed
      that: 1) in the presence of Mg2+, B and S form a stoichiometric complex, L and S
      do not form complex at all, while B and L form 2 types of complexes, probably B-L
      and 2B-L; and addition of S subfragment prevented the formation of the latter
      complex; 2) the reaction initiated by S subfragment proceeds much slower than
      that initiated by other components pointing to the possibility that in the
      absence of S L may form a nonproductive complex with B, which is slowly displaced
      by S followed by productive ternary complex formation. Dissociation constants for
      binary B-L, B-S and ternary B-L-S complexes have been estimated.

PMID- 14640967
TI  - Interaction of keratin K1 with nucleic acids on the cell surface.
AB  - The interaction of surface proteins from A431 cells and cellular extracts with
      nucleic acids was investigated using affinity modification with 32P-labeled
      reactive oligonucleotide derivatives. Proteins with molecular weights of 68, 46,
      38, and 28 kD as well as several low molecular weight proteins capable of binding
      to nucleic acids were found on the surface of intact cells. It was demonstrated
      that a protein with molecular weight of 68 kD is exposed at the cell surface,
      since the treatment of cells with trypsin results in the cleavage of this
      protein. Disruption of the integrity of the cell membrane (scrapping, treatment
      with trypsin, or permeabilization of the cell membrane with streptolysin O or
      saponin) disrupts the interaction of the reactive oligonucleotides with the cell
      surface proteins. Affinity modification of the cytosolic and membrane-cytosolic
      cell fractions with labeled oligonucleotides results in the modification of a
      large number of proteins, where proteins with molecular weights of 68, 46, 38,
      and 28 kD can be found as minor components. Surface oligonucleotide-binding
      proteins with molecular weight of ~68 kD were isolated by affinity chromatography
      after the modification of intact A431 cells with a reactive oligonucleotide
      derivative. The isolated surface oligonucleotide-binding proteins from A431 cells
      were sequenced, and one of the proteins was identified as keratin K1.

PMID- 14640968
TI  - Transport of Cl- across the plasma membrane during pollen grain germination in
      tobacco.
AB  - The role of Cl- transport across the plasma membrane was studied in an early step
      of pollen grain germination in tobacco Nicotiana tabacum L. The Cl- channel
      blockers, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and niflumic acid,
      completely suppress the germination with IC(50) approximately 8 micro M. At this
      concentration NPPB reduces the rate of Cl- efflux out of pollen grain by 1.8-fold
      in the interval 5-12 min, and niflumic acid reduces the rate 1.2-fold. 4,4;
      Diisothiocyanatostilbene-2,2;-disulfonic acid, a known inhibitor of Cl- channels
      and antiporters, completely suppresses germination as well (IC(50) = 240 micro
      M), but has no effect on the rate of Cl- efflux. Inhibitors of chloride co
      transporters, such as furosemide, bumetanide, and bis(1,3-dibutylbarbituric
      acid)pentamethine oxonol, suppress the germination by less than 50%. This set of
      data suggests that NPPB-sensitive anion channels are involved in the activation
      of pollen grains in the early stage of germination.

PMID- 14640969
TI  - Synergy of in vitro thrombolytic action of combinations of recombinant
      staphylokinase and single-chain urokinase-type plasminogen activator.
AB  - Kinetics of lysis of human plasma clots immersed in plasma were studied in vitro
      at 37 degrees C under the influence of recombinant staphylokinase, single-chain
      urokinase-type plasminogen activator (scu-PA), and their simultaneous and
      consecutive combinations. Staphylokinase and scu-PA caused concentration- and
      time-dependent lysis of the clots; 32 nM staphylokinase and 75 nM scu-PA
      separately caused 50% lysis in 4 h. At these equally effective concentrations
      staphylokinase in 4 h induced a significantly lesser exhaustion of the plasma
      plasminogen, alpha(2)-antiplasmin, and fibrinogen than scu-PA. Combinations of
      staphylokinase (<30 nM) and scu-PA (<75 nM) rendered synergic thrombolytic action
      on the clots. The synergy of thrombolytic action was more pronounced on the
      simultaneous addition of the two agents than on their consecutive addition, scu
      PA 30 min after staphylokinase. In 4 h after the addition, staphylokinase (25 nM)
      or scu-PA (15 nM) induced 24% and 2% lysis, respectively, whereas the
      simultaneous and consecutive combination of the same concentrations of these
      agents induced 58% and 50% lysis, respectively. The simultaneous combination of
      15 nM staphylokinase and 15 nM scu-PA resulted in maximal 3.8-fold increase in
      the thrombolytic effect as compared to the expected total effect of the
      individual agents. Synergic combinations of the two agents caused lesser
      exhaustion of plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen as
      compared with the expected total effect of these agents used separately. Thus,
      simultaneous and consecutive combinations of staphylokinase and scu-PA in a
      relatively narrow range of their concentrations possessed synergistic fibrin
      selective thrombolytic action on the plasma clot in vitro.

PMID- 14640970
TI  - Activity and stability of native and modified subtilisins in various media.
AB  - The activity and stability of native subtilisin 72, its complex with poly(acrylic
      acid), and subtilisin covalently attached to poly(vinyl alcohol) cryogel were
      studied in aqueous and organic media by hydrolysis of specific chromogenic
      peptide substrates. Kinetic parameters of the hydrolysis of Glp-Ala-Ala-Leu-pNA
      by native subtilisin and its complex with poly(acrylic acid) were determined.
      Based on the comparative study of stability of native and modified subtilisins in
      media of various compositions, it was established that covalent immobilization of
      subtilisin on poly(vinyl alcohol) cryogel is the most effective approach to
      improve enzyme stability in water as well as in mixtures with low water content.

PMID- 14640971
TI  - Urea induced inactivation and unfolding of arginine kinase from the sea cucumber
      Stichopus japonicus.
AB  - Urea titration was used to study the inactivation and unfolding equilibrium of
      arginine kinase (AK) from the sea cucumber Stichopus japonicus. Both fluorescence
      spectral and circular dichroism spectral data indicated that an unfolding
      intermediate of AK existed in the presence of 1.0 to 2.0 M urea. This was further
      supported by the results of size exclusion chromatography. The spectral data
      suggested that this unfolding intermediate shared many structural characteristics
      with the native form of AK including its secondary structure, tertiary structure,
      as well as its quaternary structure. Furthermore, according to the residual
      activity curve, this unfolding intermediate form still retained its catalytic
      function although its activity was lower than that of native AK. Taken together,
      the results of our study give direct evidence that an intermediate with partial
      activity exists in unfolding equilibrium states of AK during titration with urea.

PMID- 14640972
TI  - PRELI (protein of relevant evolutionary and lymphoid interest) is located within
      an evolutionarily conserved gene cluster on chromosome 5q34-q35 and encodes a
      novel mitochondrial protein.
AB  - The characterization of mitochondrial proteins is important for the understanding
      of both normal cellular function and mitochondrial disease. In the present study
      we identify a novel mitochondrial protein, PRELI (protein of relevant
      evolutionary and lymphoid interest), that is encoded within the evolutionarily
      conserved MAD3/PRELI/RAB24 gene cluster located at chromosome 5q34-q35. Mouse
      Preli is expressed at high levels in all settings analysed; it is co-expressed
      with Rab24 from a strong bi-directional promoter, and is regulated independently
      from the S-phase-specific Mad3 gene located at its 3' end. PRELI contains a stand
      alone 170 amino acid PRELI/MSF1p' motif at its N-terminus. This domain is found
      in a variety of proteins from diverse eukaryotes including yeast, Drosophila and
      mammals, but its function is unknown, and the subcellular location of higher
      eukaryotic PRELI/MSF1P' proteins has not been determined previously. We show here
      that PRELI is located in the mitochondria, and by using green-fluorescent-protein
      fusion proteins we identify a mitochondrial targeting signal at its N-terminus.

PMID- 14640973
TI  - Bicarbonate enhances alpha-synuclein oligomerization and nitration: intermediacy
      of carbonate radical anion and nitrogen dioxide radical.
AB  - alpha-Synuclein, a neuronal presynaptic protein, has been reported to undergo
      oligomerization to form toxic Lewy bodies in neurodegenerative disorders. One of
      the proposed mechanisms for aggregation of alpha-synuclein involves oxidative and
      nitrative modifications. In the present study, we show that addition of 3
      morpholino-sydnonimine chloride (SIN-1) or slow infusion of pre-formed
      peroxynitrite (ONOO-) to mixtures containing alpha-synuclein and HCO3- markedly
      enhanced both nitration and aggregation of alpha-synuclein through dityrosine
      formation. Bicarbonate-dependent peroxidase activity of Cu,Zn-superoxide
      dismutase (SOD1) also induced covalent aggregation of alpha-synuclein via a CO3*-
      dependent mechanism. Nitrone spin traps completely inhibited CO3*--mediated
      oxidation/nitration and aggregation of alpha-synuclein. Conversely, alpha
      synuclein inhibited CO3*--induced spin adduct formation. Independent evidence for
      CO3*--mediated oxidation and dimerization of alpha-synuclein was obtained from UV
      photolysis of [(NH3)5CoCO3]+, which generates authentic CO3*-. Irradiation of
      [(NH3)5CoCO3]+ and NO2- in the presence of alpha-synuclein yielded nitration and
      aggregation products that were similar to those obtained from a SIN-1 (or slowly
      infused ONOO-) and HCO3- or a myeloperoxidase/H2O2/NO2- system. Hydrophobic
      membranes greatly influenced alpha-synuclein aggregation and nitration in these
      systems. We conclude that both CO3*- and NO2* could play a major role in the
      nitration/aggregation of alpha-synuclein.

PMID- 14640974
TI  - Overexpression of phospholipase D prevents actinomycin D-induced apoptosis
      through potentiation of phosphoinositide 3-kinase signalling pathways in Chinese
      hamster ovary cells.
AB  - To examine the roles of PLD (phospholipase D) in the regulation of the apoptotic
      process, PLD1 and PLD2 were stably overexpressed in S1P3-CHO cells [CHO (Chinese
      hamster ovary) cells expressing the S1P (sphingosine 1-phosphate) receptor S1P3].
      Treatment of S1P3-CHO cells with ActD (actinomycin D) induced apoptosis, as shown
      by the occurrence of nuclear fragmentation and the caspase-dependent proteolytic
      cleavage of PARP [poly(ADP-ribose) polymerase] and protein kinase Cd.
      Overexpression of either PLD1 or PLD2 protected S1P3-CHO cells from ActD-induced
      apoptosis, as demonstrated by an increased number of viable cells and inhibition
      of PARP and protein kinase Cd cleavage. However, in the early phase of apoptosis,
      ActD induced an increase in PLD activity and activation of key factors in the
      cell-survival signalling pathways, such as PI3K (phosphoinositide 3-kinase), Akt,
      p70S6K (p70 S6 kinase) and ERK (extracellular-signal-regulated kinase).
      Furthermore, the ActD-induced activation of these survival signalling enzymes was
      potentiated by overexpression of either PLD1 or PLD2. The PI3K inhibitor LY294002
      inhibited the ActD-induced activation of Akt and p70S6K, and completely abolished
      the effects of PLD1 or PLD2, whereas inhibition of ERK activity by the MEK
      inhibitor U0126 had a milder effect. The ActD-induced activation of p70S6K and
      ERKs was blocked by 1-butanol, but not by t-butanol; similar to S1P, exogenous
      PLD suppressed the ActD-induced events in the apoptosis signalling pathways.
      These results show that, in S1P3-CHO cells, increased expression of PLDs prevents
      ActD-induced apoptosis by enhanced activation of the PI3K signalling pathways.

PMID- 14640975
TI  - Isomerization of the uncomplexed actinidin molecule: kinetic accessibility of
      additional steps in enzyme catalysis provided by solvent perturbation.
AB  - The effects of increasing the content of the aprotic dipolar organic co-solvent
      acetonitrile on the observed first-order rate constant (k(obs)) of the pre-steady
      state acylation phases of the hydrolysis of N-acetyl-Phe-Gly methyl thionester
      catalysed by the cysteine proteinase variants actinidin and papain in sodium
      acetate buffer, pH 5.3, were investigated by stopped-flow spectral analysis. With
      low acetonitrile content, plots of k(obs) against [S]0 for the actinidin reaction
      are linear with an ordinate intercept of magnitude consistent with a five-step
      mechanism involving a post-acylation conformational change. Increasing the
      acetonitrile content results in marked deviations of the plots from linearity
      with a rate minimum around [S]0=150 microM. The unusual negative dependence of
      k(obs) on [S]0 in the range 25-150 microM is characteristic of a rate-determining
      isomerization of the free enzyme before substrate binding, additional to the five
      step mechanism. There was no evidence for this phenomenon nor for the post
      acylation conformational change in the analogous reaction with papain. For this
      enzyme, however, acetonitrile acts as an inhibitor with approximately
      uncompetitive characteristics. Possible mechanistic consequences of the
      differential solvent-perturbed kinetics are indicated. The free enzyme
      isomerization of actinidin may provide an explanation for the marked difference
      in sensitivity between this enzyme and papain of binding site-catalytic site
      signalling in reactions of substrate-derived 2-pyridyl disulphide reactivity
      probes.

PMID- 14640976
TI  - The nuclear tRNA aminoacylation-dependent pathway may be the principal route used
      to export tRNA from the nucleus in Saccharomyces cerevisiae.
AB  - Nuclear tRNA export in Saccharomyces cerevisiae has been proposed to involve
      three pathways, designated Los1p-dependent, Los1p-independent nuclear
      aminoacylation-dependent, and Los1p- and nuclear aminoacylation-independent.
      Here, a comprehensive biochemical analysis was performed to identify tRNAs
      exported by the aminoacylation-dependent and -independent pathways of S.
      cerevisiae. Interestingly, the major tRNA species of at least 19 families were
      found in the aminoacylated form in the nucleus. tRNAs known to be exported by the
      export receptor Los1p were also aminoacylated in the nucleus of both wild-type
      and mutant Los1p strains. FISH (fluorescence in situ hybridization) analyses
      showed that tRNA(Tyr) co-localizes with the U18 small nucleolar RNA in the
      nucleolus of a tyrosyl-tRNA synthetase mutant strain defective in nuclear
      tRNA(Tyr) export because of a block in nuclear tRNA(Tyr) aminoacylation.
      tRNA(Tyr) was also found in the nucleolus of a utp8 mutant strain defective in
      nuclear tRNA export but not nuclear tRNA aminoacylation. These results strongly
      suggest that the nuclear aminoacylation-dependent pathway is principally
      responsible for tRNA export in S. cerevisiae and that Los1p is an export receptor
      of this pathway. It is also likely that in mammalian cells tRNAs are mainly
      exported from the nucleus by the nuclear aminoacylation-dependent pathway. In
      addition, the data are consistent with the idea that nuclear aminoacylation is
      used as a quality control mechanism for ensuring nuclear export of only mature
      and functional tRNAs, and that this quality assurance step occurs in the
      nucleolus.

PMID- 14640977
TI  - Alternative quinone substrates and inhibitors of human electron-transfer
      flavoprotein-ubiquinone oxidoreductase.
AB  - Electron-transfer flavoprotein (ETF)-ubiquinone (2,3-dimethoxy-5-methyl-1,4
      benzoquinone) oxidoreductase (ETF-QO) is a membrane-bound iron-sulphur
      flavoprotein that participates in an electron-transport pathway between eleven
      mitochondrial flavoprotein dehydrogenases and the ubiquinone pool. ETF is the
      intermediate electron carrier between the dehydrogenases and ETF-QO. The steady
      state kinetic constants of human ETF-QO were determined with ubiquinone
      homologues and analogues that contained saturated n-alkyl substituents at the 6
      position. These experiments show that optimal substrates contain a ten-carbon
      atom side chain, consistent with a preliminary crystal structure that shows that
      only the first two of ten isoprene units of co-enzyme Q10 (CoQ10) interact with
      the protein. Derivatives with saturated alkyl side chains are very good
      substrates, indicating that, unlike other ubiquinone oxidoreductases, there is
      little preference for the methyl branches or rigidity of the CoQ side chain. Few
      of the compounds that inhibit ubiquinone oxidoreductases inhibit ETF-QO.
      Compounds found to act as inhibitors of ETF-QO include 2-n-heptyl-4
      hydroxyquinoline N-oxide, a naphthoquinone analogue, 2-(3-methylpentyl)-4,6
      dinitrophenol and pentachlorophenol. 2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone (DBMIB), which inhibits the mitochondrial bc1 complex and the
      chloroplast b6 f complex in redox-dependent fashion, can serve as an electron
      acceptor for human ETF-QO. The observation of simple Michaelis-Menten kinetic
      patterns and a single type of quinone-binding site, determined by fluorescence
      titrations of the protein with DBMIB and 6-(10-bromodecyl)ubiquinone, are
      consistent with one ubiquinone-binding site per ETF-QO monomer.

PMID- 14640979
TI  - Copper stimulates trafficking of a distinct pool of the Menkes copper ATPase
      (ATP7A) to the plasma membrane and diverts it into a rapid recycling pool.
AB  - MNK (Menkes copper-translocating P-type ATPase, or the Menkes protein; ATP7A)
      plays a key role in regulating copper homoeostasis in humans. MNK has been shown
      to have a dual role in the cell: it delivers copper to cuproenzymes in the Golgi
      compartment and effluxes excess copper from the cell. These roles can be achieved
      through copper-regulated trafficking of MNK. It has previously been shown to
      undergo trafficking from the trans -Golgi network to the plasma membrane in
      response to elevated copper concentrations, and to be endocytosed from the plasma
      membrane to the trans -Golgi network upon the removal of elevated copper.
      However, the fundamental question as to whether copper influences trafficking of
      MNK to or from the plasma membrane remained unanswered. In this study we utilized
      various methods of cell-surface biotinylation to attempt to resolve this issue.
      These studies suggest that copper induces trafficking of MNK to the plasma
      membrane but does not affect its rate of internalization from the plasma
      membrane. We also found that only a specific pool of MNK can traffic to the
      plasma membrane in response to elevated copper. Significantly, copper appeared to
      divert MNK into a fast-recycling pool and prevented it from recycling to the
      Golgi compartment, thus maintaining a high level of MNK in the proximity of the
      plasma membrane. These findings shed new light on the cell biology of MNK and the
      mechanism of copper homoeostasis in general.

PMID- 14640978
TI  - Role of transient receptor potential canonical 6 (TRPC6) in non-transferrin-bound
      iron uptake in neuronal phenotype PC12 cells.
AB  - Cells take up transferrin-bound iron or NTBI (non-transferrin-bound iron). After
      treatment with NGF (nerve growth factor), PC12 cells exhibited a neuronal
      phenotype and an increase in the NTBI uptake (55Fe2+ or 55Fe3+). We loaded the
      cells with the dye calcein, whose fluorescence increases in the presence of Ca2+
      but is quenched with Fe2+ or Fe3+. When examined using calcein fluorescence or
      radioactive iron, DAG (diacylglycerol)-stimulated NTBI entry was more in NGF
      treated PC12 cells compared with untreated cells. All experiments were performed
      at 1.5 mM extracellular Ca2+. Nramp2 (natural-resistance-associated macrophage
      protein 2) mRNA expression did not change after the NGF treatment. Expression of
      the bivalent cation entry protein TRPC6 (transient receptor potential canonical
      6) was detected only in the NGF-treated cells. To verify that increased NTBI
      uptake depended on TRPC6, we examined whether transfecting HEK-293 (human
      embryonic kidney 293) cells with TRPC6 also increased the NTBI (55Fe) uptake. We
      also cotransfected HEK-293 cells with two plasmids, one expressing TRPC6 and the
      other expressing the fluorescent protein DsRED2 to identify the transfected
      cells. Challenging the calcein-loaded HEK-293 cells (which intrinsically express
      the a1-adrenergic receptors) with phenylephrine or a cell-permeant DAG increased
      the fluorescence signal more rapidly in transfected cells compared with
      untransfected cells. However, when iron (Fe2+ and Fe3+) was added before adding
      phenylephrine or DAG, the fluorescence intensity decreased more rapidly in
      transfected cells compared with untransfected cells, thereby indicating a greater
      stimulation of the NTBI uptake in cells expressing TRPC6. We postulate that the
      increase in the NTBI entry into neuronal PC12 cells is through TRPC6, a pathway
      that is unique since it is receptor-stimulated. Since neuronal cells express
      TRPC6, this pathway may have a role in neurotoxicity.

PMID- 14640980
TI  - Lipid dynamics in yeast under haem-induced unsaturated fatty acid and/or sterol
      depletion.
AB  - In the yeast Saccharomyces cerevisiae, UFA (unsaturated fatty acids) and
      ergosterol syntheses are aerobic processes that require haem. We took advantage
      of a strain affected in haem synthesis ( hem1 Delta) to starve specifically for
      one or the other of these essential lipids in order to examine the consequences
      on the overall lipid composition. Our results demonstrate that reserve lipids
      (i.e. triacylglycerols and steryl esters) are depleted independently of haem
      availability and that their UFA and sterol content is not crucial to sustain
      residual growth under lipid depletion. In parallel to UFA starvation, a net
      accumulation of SFA (saturated fatty acids) is observed as a consequence of haem
      biosynthesis preclusion. Interestingly, the excess SFA are not mainly stored
      within triacylglycerols and steryl esters but rather within specific phospholipid
      species, with a marked preference for PtdIns. This results in an increase in the
      cellular PtdIns content. However, neutral lipid homoeostasis is perturbed under
      haem starvation. The contribution of two lipid particle-associated proteins
      (namely Tgl1p and Dga1p) to this process is described.

PMID- 14640981
TI  - SIPP1, a novel pre-mRNA splicing factor and interactor of protein phosphatase-1.
AB  - We have identified a polypeptide that was already known to interact with
      polyglutamine-tract-binding protein (PQBP)-1/Npw38 as a novel splicing factor and
      interactor of protein phosphatase-1, hence the name SIPP1 for splicing factor
      that interacts with PQBP-1 and PP1 (protein phosphotase 1). SIPP1 was inhibitory
      to PP1, and its inhibitory potency was increased by phosphorylation with protein
      kinase CK1. Two-hybrid and co-sedimentation analysis revealed that SIPP1 has two
      distinct PP1-binding domains and that the binding of SIPP1 with PP1 involves a
      RVXF (Arg-Val-Xaa-Phe) motif, which functions as a PP1-binding sequence in most
      interactors of PP1. Enhanced-green-fluorescent-protein-tagged SIPP1 was targeted
      exclusively to the nucleus and was enriched in the nuclear speckles, which
      represent storage/assembly sites of splicing factors. We have mapped a nuclear
      localization signal in the N-terminus of SIPP1, while the proline-rich C-terminal
      domain appeared to be required for its subnuclear targeting to the speckles.
      Finally, we found that SIPP1 is also a component of the spliceosomes and that a
      SIPP1-fragment inhibits splicing catalysis by nuclear extracts independent of its
      ability to interact with PP1.

PMID- 14640982
TI  - Palmitoylation is not required for trafficking of human anion exchanger 1 to the
      cell surface.
AB  - AE1 (anion exchanger 1) is a glycoprotein found in the plasma membrane of
      erythrocytes, where it mediates the electroneutral exchange of chloride and
      bicarbonate, a process important in CO2 removal from tissues. It had been
      previously shown that human AE1 purified from erythrocytes is covalently modified
      at Cys-843 in the membrane domain with palmitic acid. In this study, the role of
      Cys-843 in human AE1 trafficking was investigated by expressing various AE1 and
      Cys-843Ala (C843A) mutant constructs in transiently transfected HEK-293 cells.
      The AE1 C843A mutant was expressed to a similar level to AE1. The rate of N
      glycan conversion from high-mannose into complex form in a glycosylation mutant
      (N555) of AE1 C843A, and thus the rate of trafficking from the endoplasmic
      reticulum to the Golgi, were comparable with that of AE1 (N555). Like AE1, AE1
      C843A could be biotinylated at the cell surface, indicating that a cysteine
      residue at position 843 is not required for cell-surface expression of the
      protein. The turnover rate of AE1 C843A was not significantly different from AE1.
      While other proteins could be palmitoylated, labelling of transiently transfected
      HEK-293 cells or COS7 cells with [3H]palmitic acid failed to produce any
      detectable AE1 palmitoylation. These results suggest that AE1 is not
      palmitoylated in HEK-293 or COS7 cells and can traffic to the plasma membrane.

PMID- 14640986
TI  - Molecular epidemiology of prostate cancer: androgens and polymorphisms in
      androgen-related genes.
AB  - In most western countries prostate cancer is the most commonly diagnosed non-skin
      cancer in men. Despite its high morbidity and mortality the etiology of prostate
      cancer remains obscure. The involvement of androgens has been examined
      extensively in prostate carcinogenesis but the results of most epidemiological
      studies remain inconclusive. This review focuses on current perspectives of
      androgen levels and polymorphisms in androgen-related genes. Racial differences
      in genetic polymorphisms that have a role in the biosynthesis and metabolism of
      androgens may partly account for racial differences in prostate cancer risk.
      Reasons are also given for inconsistent results in molecular epidemiological
      studies and insights and directions for future research are discussed. The
      development of a polygenic model for prostate cancer, incorporating multiple loci
      from the individual genes, may maximize the chance of identifying individuals
      with high-risk genotypes, resulting in better preventive, diagnostic, and
      therapeutic strategies.

PMID- 14640983
TI  - Activation of the DNA-binding ability of latent p53 protein by protein kinase C
      is abolished by protein kinase CK2.
AB  - p53 is one of the most important regulators of cell proliferation and
      differentiation and of programmed cell death, triggering growth arrest and/or
      apoptosis in response to different cellular stress signals. The sequence-specific
      DNA-binding function of p53 protein can be activated by several different stimuli
      that modulate the C-terminal domain of this protein. The predominant mechanism of
      activation of p53 sequence-specific DNA binding is phosphorylation at specific
      sites. For example, phosphorylation of p53 by PKC (protein kinase C) occurs in
      undamaged cells, resulting in masking of the epitope recognized by monoclonal
      antibody PAb421, and presumably promotes steady-state levels of p53 activity in
      cycling cells. In contrast, phosphorylation by cdk2 (cyclin-dependent kinase
      2)/cyclin A and by the protein kinase CK2 are both enhanced in DNA-damaged cells.
      We determined whether one mechanism to account for this mutually exclusive
      phosphorylation may be that each phosphorylation event prevents modification by
      the other kinase. We used non-radioactive electrophoretic mobility shift assays
      to show that C-terminal phosphorylation of p53 protein by cdk2/cyclin A on Ser315
      or by PKC on Ser378 can efficiently stimulate p53 binding to DNA in vitro, as
      well as binding of the monoclonal antibody Bp53-10, which recognizes residues 371
      380 in the C-terminus of p53. Phosphorylation of p53 by CK2 on Ser392 induces its
      DNA-binding activity to a much lower extent than phosphorylation by cdk2/cyclin A
      or PKC. In addition, phosphorylation by CK2 strongly inhibits PKC-induced
      activation of p53 DNA binding, while the activation of p53 by cdk2/cyclin A is
      not affected by CK2. The presence of CK2-mediated phosphorylation promotes PKC
      binding to its docking site within the p53 oligomerization domain, but decreases
      phosphorylation by PKC, suggesting that competition between CK2 and PKC does not
      rely on the inhibition of PKC-p53 complex formation. These results indicate the
      crucial role of p53 C-terminal phosphorylation in the regulation of its DNA
      binding activity, but also suggest that antagonistic relationships exist between
      different stress signalling pathways.

PMID- 14640987
TI  - Effective treatment of bone metastases from a neuroendocrine tumour of the
      pancreas with high activities of Indium-111-pentetreotide.
AB  - OBJECTIVE: To evaluate therapy with high doses of (111)Indium pentetreotide in a
      patient with bone metastases from a carcinoid of the pancreas. CASE REPORT: A 55
      Year-old male presented in November 1990 with stomach ache with dorsal
      irradiation. Ultrasonography and computed tomography (CT-) scans of the abdomen
      revealed a tumour of the tail of the pancreas and liver metastases. Histological
      examination revealed a neuroendocrine tumour. Surgery and polychemotherapy were
      initiated and after seven cycles a tumour regression of 30% was achieved. During
      follow-up multiple metastases were seen upon bone scintigraphy for which
      treatment with high doses Indium-111-octreotide was initiated. MATERIALS AND
      METHODS: The patient underwent eight cycles, with one cycle every 5 weeks. Each
      treatment consisted of an i.v. injection of 6 GBq Indium-111-pentetreotide.
      Comparing the results of the first and the last post-treatment scintigraphy, a
      regression of the number and intensity of uptake in the lesions was found. Bone
      scintigraphy showed a regression of the skeletal lesions as well, while X-ray, CT
      scan and chromogranin-A levels showed stable disease. CONCLUSION: Results from
      the treatment of our patient indicate that the use of high dose radiolabelled
      somatostatin analogues could be of significant use, even in the case of bone
      metastases. To our knowledge, this is the first report describing therapeutic
      effects on bone metastases from a neuroendocrine tumour.

PMID- 14640988
TI  - Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on
      thyroid function and volume evaluated by a randomized clinical trial.
AB  - OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD)
      might possess a radioprotective effect, leading to a higher rate of recurrence of
      hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical
      trial was performed to clarify whether resumption of methimazole after (131)I
      influences the final outcome of this treatment. METHODS: We assigned 149 patients
      with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD)
      or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy,
      all patients were rendered euthyroid by methimazole, which was discontinued 4
      days before the (131)I therapy. RESULTS: During the follow-up period of 12
      Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had
      recurrence of hyperthyroidism in the +ATD group; the respective numbers in the 
      ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum
      free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval
      (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95%
      CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup
      that remained euthyroid during follow-up, thyroid Volume reduction, assessed by
      ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)]
      than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No
      radioprotective effect could be demonstrated, with regard to final thyroid
      function, for the resumpton of methimazole 7 days after (131)I therapy. Although
      resumption of methimazole slightly reduced the magnitude of shrinkage of the
      goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the
      early period after radiation favours this regimen.

PMID- 14640989
TI  - The usefulness of 99mTc-SestaMIBI scan in the diagnostic evaluation of thyroid
      nodules with oncocytic cytology.
AB  - OBJECTIVE: To assess the relevance of (99m)Tc-SestaMIBI (MIBI) scan in the
      diagnostic evaluation of thyroid nodules with oncocytic cytology. SUBJECTS AND
      METHODS: Twenty-four patients with a single (or prevalent) 'cold' solid nodule
      with Hurthle cells (HC) at fine needle aspiration cytology (FNAC) were studied.
      Cytological diagnosis of oncocytic metaplasia (OM) or HC tumor (HCT) was made
      when HC on the smear were comprised 10-75%, or >75%. Nodules concentrating MIBI
      at early and late (2 h after washout) stages were considered MIBI-positive. In
      all cases histological findings were obtained after total thyroidectomy. RESULTS:
      FNAC was malignant or suspect for malignancy in 16 cases (six HCT and 10 OM) and
      not suspect in eight (two HCT and six OM). Histological examination revealed 14
      malignant tumors (11 HCT and three OM), and 10 benign thyroid lesions (three HCT
      and seven OM). Sensitivity of FNAC for malignancy was 92.8% and specificity was
      70.0%; HCT were identified by FNAC in only 35.7% and OM in 70.0% of cases. No
      significant difference in MIBI positivity was found between malignant and benign
      thyroid nodules. The highest percentage of MIBI positivity was found in HCT
      (78.5%), but MIBI-positive nodules were also observed in thyroid lesions with HC
      metaplasia (40.0%). CONCLUSIONS: MIBI scintiscan has no value in differentiating
      malignant from benign HC thyroid neoplasias. Most HCT are MIBI-positive, but this
      scan is not sufficiently specific to differentiate true HC neoplasias from other
      thyroid lesions showing HC at FNAC, although an MIBI-negative scan strongly
      supports the absence of true HCT.

PMID- 14640990
TI  - Circulating IGF-I levels in monitoring and predicting efficacy during long-term
      GH treatment of GH-deficient adults.
AB  - OBJECTIVE: To investigate the effects of long-term GH in GH-deficient adults, as
      predicted by IGF-I levels. METHODS: Patients received GH, 5 microg/kg per day for
      1 Month and 10 microg/kg per day for another 12-30 Months. Changes in body
      composition, cardiac structure/function, serum lipids and quality of life were
      measured. RESULTS: There was a significant increase in lean body mass (LBM) (2.21
      kg; P<0.0001) after 6 Months, which was sustained throughout treatment. A larger
      increase occurred in males than females (2.97 vs 1.19 kg; P<0.0001). Total fat
      mass was reduced (2.56 kg; P<0.0001 (3.26 kg males, 1.63 kg females)).
      Responsiveness to GH varied greatly, but LBM changes correlated with IGF-I
      changes (P<0.004). Furthermore, thinner patients experienced greater and
      progressive LBM increases. There was an increase in ejection fraction (3.85+/
      9.95%; P=0.0002) after 6 Months, sustained to 18 Months. These cardiac effects
      were equal for males and females, and did not correlate with IGF-I levels. Serum
      low-density lipoprotein/high-density lipoprotein ratios decreased within 6
      Months, and were sustained thereafter. Quality of life improved significantly
      after 6 Months, an effect that was sustained/enhanced as treatment continued. No
      major adverse events were identified. CONCLUSIONS: Improved body composition is
      both reflected by IGF-I changes and predicted inversely by baseline adiposity.
      Other effects of GH replacement on cardiac function, dyslipidaemia and quality of
      life, however, do not correlate with circulating IGF-I concentrations. Our
      findings validate the importance of sustained GH therapy, but caution on the
      interpretation of IGF-I levels in monitoring the long-term effects of GH
      treatment.

PMID- 14640991
TI  - Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in
      previously untreated GH-deficient adults.
AB  - OBJECTIVE: Previous studies evaluating the lipolytic effect of GH have in general
      been performed in subjects on chronic GH therapy. In this study we assessed the
      lipolytic effect of GH in previously untreated patients and examined whether the
      negative effect of enhanced lipolysis on glucose metabolism could be counteracted
      by acute antilipolysis achieved with acipimox. METHODS: Ten GH-deficient (GHD)
      adults participated in four experiments each, during which they received in a
      double-blind manner: placebo (A); GH (0.88+/-0.13 mg) (B); GH+acipimox 250 mg
      b.i.d. (C); and acipimox b.i.d. (no GH) (D), where GH was given the night before
      a 2 h euglycemic, hyperinsulinemic clamp combined with infusion of [3
      (3)H]glucose and indirect calorimetry. RESULTS: GH increased basal free fatty
      acid (FFA) levels by 74% (P=0.0051) and insulin levels by 93% (P=0.0051). This
      resulted in a non-significant decrease in insulin-stimulated glucose uptakes
      (16.61+/-8.03 vs 12.74+/-5.50 micromol/kg per min (s.d.), P=0.07 for A vs B). The
      rates of insulin-stimulated glucose uptake correlated negatively with the FFA
      concentrations (r=-0.638, P<0.0001). However, acipimox caused a significant
      improvement in insulin-stimulated glucose uptake in the GH-treated patients
      (17.35+/-5.65 vs 12.74+/-5.50 micromol/kg per min, P=0.012 for C vs B). The
      acipimox-induced enhancement of insulin-stimulated glucose uptake was mainly due
      to an enhanced rate of glucose oxidation (8.32+/-3.00 vs 5.88+/-2.39 micromol/kg
      per min, P=0.07 for C vs B). The enhanced rates of glucose oxidation induced by
      acipimox correlated negatively with the rate of lipid oxidation in GH-treated
      subjects both in basal (r=-0.867, P=0.0093) and during insulin-stimulated (r=
      0.927, P=0.0054) conditions. GH did not significantly impair non-oxidative
      glucose metabolism (6.86+/-5.22 vs 8.67+/-6.65 micromol/kg per min, P=NS for B vs
      A). The fasting rate of endogenous glucose production was unaffected by GH and
      acipimox administration (10.99+/-1.98 vs 11.73+/-2.38 micromol/kg per min, P=NS
      for B vs A and 11.55+/-2.7 vs 10.99+/-1.98 micromol/kg per min, P=NS for C vs B).
      On the other hand, acipimox alone improved glucose uptake in the untreated GHD
      patients (24.14+/-8.74 vs 16.61+/-8.03 micromol/kg per min, P=0.0077 for D vs A)
      and this was again due to enhanced fasting (7.90+/-2.68 vs 5.16+/-2.28
      micromol/kg per min, P=0.01 for D vs A) and insulin-stimulated (9.78+/-3.68 vs
      7.95+/-2.64 micromol/kg per min, P=0.07 for D vs A) glucose oxidation.
      CONCLUSION: The study of acute administration of GH to previously untreated GHD
      patients provides compelling evidence that (i) GH-induced insulin resistance is
      mainly due to induction of lipolysis by GH; and (ii) inhibition of lipolysis can
      prevent the deterioration of insulin sensitivity. The question remains whether GH
      replacement therapy should, at least at the beginning of therapy, be combined
      with means to prevent an excessive stimulation of lipolysis by GH.

PMID- 14640992
TI  - Insulin sensitivity and glucose tolerance improve in patients with acromegaly
      converted from depot octreotide to pegvisomant.
AB  - AIM AND METHOD: Insulin resistance leading, in some cases, to glucose intolerance
      is an important contributory factor to the cardiovascular morbidity and mortality
      associated with acromegaly. The aim of this study was to document changes in
      insulin sensitivity (IS) in a group of seven patients with acromegaly (three
      male, four female, mean+/-s.d. age 59+/-13 Years) treated initially with a stable
      dose of depot octreotide (OT; median dose 30 mg four times weekly, range 10-30
      mg) for a median of 18 Months (range 16-19 Months) and who were then transferred
      to treatment with pegvisomant (median dose 15 mg daily, range 10-20 mg) for a
      median of 8 Months (range 7-9 Months). IS was assessed by homeostatic model
      assessment (HOMA) using fasting glucose and insulin concentrations and by a short
      insulin tolerance test (sITT). Body composition was assessed by dual energy X-ray
      absorptiometry. RESULTS: Mean+/-s.d. serum IGF-I concentrations during therapy
      with OT and with pegvisomant were not statistically different (283+/-119 ng/ml on
      OT vs 191+/-39 ng/ml on pegvisomant (P=0.4)). However, mean+/-s.d. fasting plasma
      glucose fell from 6.2+/-1.0 mmol/l on OT to 5.2+/-0.6 mmol/l on pegvisomant
      (P=0.017) and was lower on pegvisomant in all seven patients. In four patients,
      fasting plasma glucose fell from values diagnostic of diabetes mellitus or
      impaired fasting glucose on OT to within the normal range on pegvisomant. Mean+/
      s.d. peripheral IS (by sITT) increased from 139+/-39 micromol/l per min on OT to
      169+/-59 micromol/l per min on pegvisomant (P=0.037). Mean+/-s.d. IS (by HOMA %S)
      was unchanged over the course of the study (149.1+/-43.7% on OT vs 139.9+/-76.6%
      on pegvisomant, P=0.28). Mean+/-s.d. pancreatic beta-cell secretory function
      (HOMA %B) improved significantly on pegvisomant compared with OT (49.4+/-19.2% vs
      82.4+/-43.5%, P=0.01). No statistically significant change in total fat (P=0.3),
      % fat (P=0.28) or circulating non-esterified fatty acids (P=0.35) was observed.
      CONCLUSIONS: IS and glucose tolerance improved in patients converted from OT
      therapy to pegvisomant, without a change in body composition and even when serum
      IGF-I concentrations remained equally well controlled. This may be an important
      factor in the choice of medical therapy for patients with acromegaly.

PMID- 14640993
TI  - Impaired adrenocortical function in very low birth weight infants after multiple
      pregnancies.
AB  - OBJECTIVE: To evaluate the differences in adrenal function between very low birth
      weight (VLBW) infants from singleton and multiple pregnancies. DESIGN AND
      METHODS: Forty infants of birth weights less than 1500 g underwent an ACTH test.
      Thirty infants born from singleton pregnancies (singleton group) and ten born
      from multiple pregnancies (multiple group) were enrolled. A baseline blood sample
      was drawn for cortisol measurement and thereafter serum cortisol was measured 1
      and 2 h after an i.v. injection of ACTH. RESULTS: In multiple pregnancies, the
      median basal cortisol level of the infants was significantly lower than that in
      the singletons. The median cortisol level at 1 and 2 h after administration of
      ACTH was significantly lower in infants from multiple gestations than in
      singletons. Of infants from the multiple gestation group six, and of the
      singleton infants 12, had baseline cortisol levels lower than the reference
      values (P=0.48). One hour after ACTH stimulation all multiple and 53% of the
      singleton group infants showed a subnormal (<500 nmol/l, P=0.007) cortisol
      response. Two hours after ACTH, nine multiple group patients and 43% of the
      singletons had subnormal (<500 nmol/l, P=0.01) stimulated cortisol levels.
      CONCLUSIONS: We have concluded that VLBW infants from multiple gestations seem to
      be at an increased risk of insufficient postnatal adrenocortical function. In the
      future, specific attention should be paid to evaluate further newborn infants
      from multiple pregnancies with regard to a possible benefit of hydrocortisone
      substitution in stressful clinical situations.

PMID- 14640994
TI  - Is the plasma ACTH concentration a reliable parameter in the insulin tolerance
      test?
AB  - OBJECTIVE: The insulin tolerance test (ITT) is an established standardized test
      for the evaluation of the hypothalamic-pituitary-adrenal axis. While a peak
      cortisol value of >18 microg/dl is usually interpreted as a sufficient response
      to the ITT, the plasma ACTH response has not yet been standardized. METHODS: We
      evaluated retrospectively the peak plasma ACTH concentrations during 140 ITTs in
      125 patients with suspected pituitary insufficiency and prospectively in 15
      healthy subjects. RESULTS: All healthy subjects had a peak cortisol concentration
      >/=18 microg/dl; 32 of 125 tests in the patients showed an insufficient cortisol
      response (peak cortisol concentration <18 microg/dl). The peak stimulated ACTH
      concentration in patients with secondary adrenal insufficiency (SAI) was 49.2+/
      37.2 pg/ml (mean+/-s.d.) vs 130.9+/-89.3 pg/ml in patients without SAI, and
      110.9+/-55.4 pg/ml in normal subjects (P<0.001). There was a weak, but
      significantly positive correlation between the peak ACTH and peak cortisol
      concentrations (rho=0.446, P<0.001), but there was also a very wide spread of the
      values. Defining a cut-off value for the peak plasma ACTH concentration with a
      sufficient sensitivity and specificity to identify patients with an impaired
      hypothalamic-pituitary-adrenal (HPA) axis was not possible. A peak plasma ACTH
      <20 pg/ml as a cut-off value had a sensitivity of 25% and a specificity of 98%
      for SAI. A cut-off value of a peak plasma ACTH <140 pg/ml had a sensitivity of
      97% but a low specificity of 39%. CONCLUSIONS: Although there is a significant
      positive correlation between the peak ACTH and the peak cortisol concentrations,
      we conclude that there is no additional benefit in determining the ACTH
      concentrations during an ITT. Because of the strong variations of the values, the
      peak ACTH concentration is a poor parameter for the evaluation of the HPA axis.

PMID- 14640995
TI  - Hepatic steatosis in Cushing's syndrome: a radiological assessment using computed
      tomography.
AB  - OBJECTIVE: Hepatic steatosis may occur in association with insulin resistance and
      obesity, two features commonly seen in Cushing's syndrome (CS). The aim of this
      report is to assess the prevalence of hepatic steatosis in patients with active
      CS using computed tomography (CT) and to identify any associations between
      hepatic steatosis, endocrine and biochemical variables and body fat distribution.
      PATIENTS AND MEASUREMENTS: We identified 50 patients with active CS in whom
      appropriate CT was available to allow measurement of liver and spleen
      attenuation. In 26 patients, abdominal fat measurements were also available.
      Serum markers of CS and liver function tests were recorded. RESULTS: Ten of 50
      patients had a liver-to-spleen CT attenuation ratio (L/S) of less than 1,
      indicating hepatic steatosis. There was a significant negative correlation
      between both liver attenuation and L/S ratio with total abdominal fat area,
      visceral fat area, the percentage of visceral fat and the visceral to
      subcutaneous fat ratio; the strongest negative correlation was found between
      visceral fat area and L/S ratio (r=-0.638, P<0.001, n=26). L/S ratio positively
      correlated with alkaline phosphatase levels (r=+0.423, P=0.044, n=23) but with no
      other serum marker of CS activity or liver enzyme. CONCLUSIONS: We have
      demonstrated hepatic steatosis on CT in 20% of patients with active CS. The
      presence of hepatic steatosis was significantly correlated with total abdominal
      fat area and visceral fat area.

PMID- 14640996
TI  - Elevated plasma endothelin as an additional cardiovascular risk factor in
      patients with Cushing's syndrome.
AB  - BACKGROUND: Recently the pathophysiological role of endothelin (ET) has been
      presumed in a number of adrenal disorders such as primary hyperaldosteronism,
      pheochromocytoma and adrenocortical insufficiency. AIM: The aim of the present
      study was to evaluate circulating ET-1 levels in patients with endogenous
      Cushing's syndrome. METHODS AND RESULTS: Plasma ET-1 levels were determined by
      highly sensitive RIA. Thirteen untreated subjects with Cushing's syndrome were
      studied: eight women and five men of mean age 44.2+/-9.5 Years (s.d.). In ten of
      them, Cushing's disease had been diagnosed and three had adrenal adenomas. ET-1
      was 3-fold higher in the patient group than in age-matched healthy controls
      (n=13): 1.59+/-0.78 vs 0.46+/-0.20 pmol/l respectively, P<0.001. In adrenal
      adenoma patients, ET-1 was not significantly higher than in the Cushing's disease
      subjects (1.84+/-0.67 vs 1.51+/-0.83 pmol/l respectively, P>0.05). In three
      patients who died of severe cardiovascular complications, plasma ET-1 was
      significantly higher than in the remaining patients (2.34+/-0.35 pmol/l, P<0.05).
      A positive correlation was found between the total cholesterol (6.94+/-1.75
      mmol/l) and ET-1 levels in the patients with Cushing's syndrome: r=+0.73, P<0.02.
      No correlation was observed, however, between the levels of ET-1 and blood
      pressure (183+/-37/106+/-18 mmHg), plasma cortisol levels (455.2+/-74.5 nmol/l)
      or urinary cortisol excretion (1463+/-726 nmol/24 h). The successful treatment
      and correction of hypercortisolism in seven patients led to insignificant
      reduction in plasma ET from 1.34+/-0.69 to 0.73+/-0.53 pmol/l, P>0.05.
      CONCLUSION: Our results clearly demonstrate that the ET system is activated in
      Cushing's syndrome. Elevated plasma ET-1 levels probably play a role in the
      pathogenesis of accelerated and early atherosclerosis development in this
      disorder.

PMID- 14640997
TI  - Increases in plasma levels of atrial and brain natriuretic peptides after running
      a marathon: are their effects partly counterbalanced by adrenocortical steroids?
AB  - OBJECTIVE: Long-distance running results in considerable stress. Little evidence
      exists about the role of the atrial and brain natriuretic peptides, ANP and BNP,
      deriving from the myocardium. The aim of our study was to investigate the
      influence of running 42.195 km on changes in circulating natriuretic propeptides
      and adrenocortical steroids. DESIGN AND METHODS: We studied 17 male and 2 female
      runners (age: 28-62 Years) participating in a marathon. Blood samples were
      obtained before and immediately after the competition. proANP(1-98) and proANP(1
      30) as well as Nt-proBNP(8-29) were determined by enzyme immunoassays. RESULTS:
      Runners finished the competition between 2 h 58 min and 4 h 25 min. We observed a
      more pronounced increase in proANP(1-98) (+58%) and proANP(1-30) (+99%, both
      P<0.001) compared with Nt-proBNP(8-29) (+6%; P=0.005). Increases in proANP(1-30)
      positively correlated with runners' age (r=0.53; P=0.02). We also observed a
      marked increase in cortisol (+73%) and especially in aldosterone (+431%, both
      P<0.001). CONCLUSIONS: Cardiac strain during long-distance running may explain
      the pronounced increase in proANP. Other explanations for the observed rise in
      plasma levels might be a change in the permeability of myocardial cells and an
      impaired clearance. A rise in adrenocortical steroids may compensate for the
      negative influence of ANP on natriuresis and blood pressure. Positive effects of
      ANP during a marathon could be the regulation of body temperature by influencing
      sweat glands as well as the stimulation of lipolysis compensating for the
      enormous energy demand.

PMID- 14640998
TI  - Computed tomography assessment of fat distribution in male and female patients
      with Cushing's syndrome.
AB  - OBJECTIVE: Our aims were to describe the abdominal fat distribution in male
      patients with Cushing's syndrome (CS) on computerised tomography (CT), to compare
      our findings with non-cushingoid patients, to validate previous reports of
      increased visceral fat in female patients with CS and to identify any
      correlations between fat distribution and biochemical findings. DESIGN:
      Retrospective and observational. PATIENTS: Appropriate CT scans were identified
      in 31 patients (seven male) with active CS. MEASUREMENTS: Total, visceral and
      subcutaneous fat areas were obtained. The percentage of visceral fat and the
      visceral to subcutaneous fat ratio (V:S ratio) were calculated. Biochemical data
      were recorded. Control data of fat distribution were obtained from the
      literature. RESULTS: There was a significant increase in the V:S ratio in male
      patients with CS when compared with non-cushingoid controls (1.175+/-0.59 vs
      0.77+/-0.39, 95% confidence interval (CI) 0.0817-0.728). There was a significant
      increase in the V:S ratio in female patients with CS (0.845+/-0.53 vs 0.38+/
      0.19, 95% CI 0.269-0.661). There was no difference in the V:S ratio between male
      and female patients with CS (1.175+/-0.59 vs 0.845+/-0.53, 95% CI -0.144-0.804).
      No significant correlations between fat distribution and glucose levels,
      circulating cortisol, ACTH or lipids were found. CONCLUSIONS: Our data
      demonstrate an increase in visceral fat distribution in both male and female
      patients with CS, with the abolition of the normal male to female difference in
      visceral fat. Increased visceral fat may increase the risk of the metabolic
      syndrome in this group of patients.

PMID- 14640999
TI  - Birthsize, gestational age and adrenal function in adult life: studies of
      dexamethasone suppression and ACTH1-24 stimulation.
AB  - OBJECTIVE: Several studies show that low birthweight is associated with long-term
      alterations in the function of the hypothalamic-pituitary-adrenal axis (HPAA). We
      recently reported that the relationship between birthweight and fasting serum
      cortisol concentrations differed according to the gestational age of the babies,
      suggesting that both hypercortisolism and hypocortisolism could be a consequence
      of impaired fetal growth. We have now extended these findings by examining the
      relationship between birthweight, gestational age and tests of adrenal
      suppression and stimulation. DESIGN: Prospective birth cohort study. SUBJECTS AND
      METHODS: We studied 165 women (mean age 71.3 Years) born at term in Helsinki,
      Finland, between 1924 and 1933, whose body size and gestational age at birth were
      recorded. These women underwent an overnight 0.25 mg dexamethasone suppression
      test followed by a 1 microg ACTH(1-24) stimulation test. RESULTS: In all women
      combined, low birthweight was associated with lower total (P=0.03) and free
      (P=0.02) cortisol concentrations following dexamethasone. However, these
      relationships were dependent on gestational age at birth, interactions between
      the effects of birth size and gestational age on dexamethasone responsiveness
      being statistically significant. To demonstrate these interactions, we divided
      the study population into two groups according to gestational age. In subjects
      born at 40 weeks of gestation or more, low birthweight was strongly associated
      with enhanced dexamethasone suppression (P=0.003 for total and P=0.0004 for free
      cortisol), while in subjects born before 40 weeks of gestation there was no
      association. There was, however, no correlation between birth size and the
      adrenal response to ACTH(1-24). CONCLUSIONS: These findings reinforce our
      suggestions that events during prenatal life may lead to both up-regulation and
      down-regulation of the HPAA.

PMID- 14641000
TI  - Do patients with multiple endocrine neoplasia syndrome type 1 benefit from
      periodical screening?
AB  - OBJECTIVE: To determine the benefit of periodical clinical screening of carriers
      of a mutation in the multiple endocrine neoplasia type 1 (MEN-1) gene, because
      any useful discussion requires more concrete data. DESIGN AND METHODS: Our study
      population consisted of all the patients with MEN-1 (n=58) who were treated at
      the University Medical Centre Utrecht, The Netherlands, during the period 1975
      2003, and their affected relatives (n=29). Records of affected individuals who
      died were analysed for morbidity, cause of death and age at death. We discuss our
      results in the light of the literature on MEN-1 regarding the benefit of
      screening. RESULTS: Over a period of 28 Years, we identified 87 individuals
      affected with MEN-1, from 16 families. A mutation in the MEN-1 gene was detected
      in 57%, 18% were obligate carriers, and in 24% the diagnosis was only clinically
      confirmed. Thirty individuals died, 17 from MEN-1-related causes, including
      malignancies (n=12: pancreatic islet cell tumours n=6 and carcinoid tumours n=6),
      the Zollinger-Ellison syndrome (n=4) and Cushing's disease (n=1). The remaining
      patients died of causes probably related to MEN-1 (n=3), unrelated to MEN-1 (n=7)
      or of unknown causes. Mean ages at death from MEN-1 were 55.4 Years for men and
      46.8 Years for women, in both cases significantly lower than the mean age at
      death in the average Dutch population (P<0.05). CONCLUSIONS: We feel that the
      significantly increased risk of premature death found in patients with MEN-1
      justifies the periodical clinical screening of carriers of the MEN-1 gene
      mutation. Early detection and treatment of abnormalities will probably reduce
      this risk.

PMID- 14641001
TI  - Endogenous sex hormones in men aged 40-80 years.
AB  - OBJECTIVE: To determine the relationship between aging, life-style factors and
      health-related factors and endogenous sex hormone levels. DESIGN: Cross-sectional
      study of 400 independently living men between 40 and 80 Years of age. METHODS:
      After exclusion of subjects who were not physically or mentally able to visit the
      study center, 400 men were randomly selected from a population-based sample.
      Total testosterone (TT), bioavailable testosterone (BT) (i.e. not bound to sex
      hormone-binding globulin (SHBG)), SHBG, estradiol (E(2)) and
      dehydroepiandrosterone-sulfate (DHEA-S) were investigated for their relationship
      with age, body mass index (BMI), waist circumference, smoking, physical activity
      and general health status. Multivariate models using ANCOVA analyses were used to
      examine the contribution of life-style factors to sex hormone variability.
      RESULTS: TT, BT and DHEA-S decreased with age; 0.2, 0.7 and 1.2%/Year
      respectively. SHBG showed an increase with age of 1.1%/Year. No changes with age
      were found for E(2). General health status modified the association of TT and
      SHBG with age (P interaction 0.10 and 0.002 respectively). Increased BMI and
      waist circumference were associated with decreased TT, BT, SHBG and DHEA-S and
      increased E(2) (all P<0.01). Current smoking, lower alcohol intake and a higher
      physical activity score were associated with higher TT and SHBG levels.
      CONCLUSION: This study showed the important determinants of sex hormones were
      age, BMI, waist circumference, smoking, general health status and physical
      activity. Furthermore, it can be concluded that general health status modified
      the effect between sex hormones and age. For future observational studies it
      should be taken into account that the above-mentioned determinants may alter the
      association between sex hormones and diseases and related conditions.

PMID- 14641002
TI  - Vitamin D receptor polymorphisms: no association with type 1 diabetes in the
      Finnish population.
AB  - OBJECTIVE: The effect of polymorphisms of the vitamin D receptor (VDR) gene on
      susceptibility to type 1 diabetes has recently been investigated extensively.
      Several findings on positive disease associations have been observed and, in
      addition, a protective effect of vitamin D supplementation has been reported.
      DESIGN: We studied the effect of three vitamin D receptor gene polymorphisms
      (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control
      series (more than 2000 controls and about 1000 patients) from the Finnish
      population. METHODS: A combination of case-control and affected-family based
      approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and
      VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction.
      RESULTS: A few borderline significant associations were observed with both
      approaches used. In the case-control association analyses we found significant
      differences between cases and controls in frequencies of VDRB (P=0.024, all
      subjects and P=0.016, HLA DQB1*0302-positive subjects) and VDRF (P=0.0063, Turku
      cohort). In the total family set a decreased (39.3%) transmission of the VDRA
      VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1
      2 to sons was seen (P=0.0059 and P=0.024 respectively). Transmission of the
      haplotype 2-2-1 to daughters was decreased (37.6%, P=0.022). Interestingly, we
      also observed significant differences in allele frequencies of the polymorphisms
      studied between populations from three different regions in Finland. CONCLUSIONS:
      All these differences disappeared after correction for multiple testing. We
      conclude that the single nucleotide polymorphisms analysed are unlikely to be
      associated with type 1 diabetes in the Finnish population.

PMID- 14641003
TI  - Androgen receptor gene exon 1 CAG repeat polymorphism in Finnish patients with
      childhood-onset type 1 diabetes.
AB  - OBJECTIVE: Animal models suggest that androgen receptor gene polymorphisms might
      affect disease predisposition in human immune-mediated diabetes. The aim of this
      study was to investigate the effect of the human androgen receptor gene exon 1
      CAG repeat polymorphisms on type 1 diabetes (T1D) susceptibility. DESIGN AND
      METHODS: A combined strategy of case-control and family-based approaches was
      used. Affected sibling pair families (n=120), nuclear families (n=645) and
      cohorts of sporadic cases (n=208) and controls (n=1381) were genotyped for
      androgen receptor gene exon 1 CAG repeat polymorphism. An automated fluorescence
      based DNA fragment-sizing method was used. RESULTS: The distribution of CAG
      repeat alleles did not differ significantly between patients and controls.
      However, short repeat alleles (7-14) were more prevalent among cases in girls
      compared with controls (8.77% vs 5.91%; P=0.03). Long repeat alleles (19-28) were
      less frequent among HLA DR3-positive diseased boys than in DR3-positive control
      boys (32.6% vs 40.6%; P=0.011). The differences were not significant after
      adjustment for multiple comparisons. Transmission of CAG repeat alleles was not
      different from expected in the total material. However, transmissions to girls
      deviated from the expected value significantly (extended transmission
      disequilibrium test (ETDT) 37.82; P=0.0016). A decreased transmission of the
      alleles with 13, 20 and 26 repeats to girls was observed (T%0, P=0.046; T%25.5,
      P=0.0003, T%0, P=0.025). CONCLUSION: The results do not support a common role for
      the androgen receptor gene exon 1 CAG repeat in T1D susceptibility; however, an
      effect of a disease variant in linkage disequilibrium could be detected.

PMID- 14641004
TI  - Sex hormones, inflammation and the metabolic syndrome: a population-based study.
AB  - OBJECTIVE: Mild hypoandrogenism in men is associated with features of the
      metabolic syndrome, but the association with the metabolic syndrome itself using
      an accepted definition has not been described. DESIGN: Men with the metabolic
      syndrome were identified and testosterone and sex hormone-binding globulin (SHBG)
      levels were determined in a population-based cohort of 1896 non-diabetic middle
      aged Finnish men. RESULTS: Calculated free testosterone and SHBG were 11% and 18%
      lower (P<0.001) in men with the metabolic syndrome (n=345, World Health
      Organisation definition). After categorisation by tertiles and adjusting for age
      and body mass index, total and free testosterone and SHBG were inversely
      associated with concentrations of insulin, glucose, triglycerides, C-reactive
      protein (CRP) and CRP-adjusted ferritin and positively associated with high
      density lipoprotein cholesterol. Men with free testosterone levels in the lowest
      third were 2.7 (95% confidence interval (CI) 2.0-3.7) times more likely to have
      the metabolic syndrome in age-adjusted analyses, and 1.7 (95% CI 1.2-2.4) times
      more likely even after further adjusting for body mass index. Exclusion of men
      with cardiovascular disease did not alter the association. The inverse
      association of SHBG with the metabolic syndrome was somewhat stronger.
      CONCLUSIONS: Low testosterone and SHBG levels were strongly associated not only
      with components of the metabolic syndrome, but also with the metabolic syndrome
      itself, independently of body mass index. Furthermore, sex hormones were
      associated with inflammation and body iron stores. Even in the absence of late
      stage consequences such as diabetes and cardiovascular disease, subtle
      derangements in sex hormones are present in the metabolic syndrome, and may
      contribute to its pathogenesis.

PMID- 14641005
TI  - The molecular machinery of Keilin's respiratory chain.
AB  - Keilin's classic paper of 1925 [Keilin (1925) Proc. R. Soc. London Ser. B 100,
      129-151], achieved with simple, but elegant, techniques, describes the cytochrome
      components of the respiratory chain and their roles in intracellular respiration
      and oxygen consumption. Since that time, a tremendous amount of work has
      clarified the intricate details of the prosthetic groups, cofactors and proteins
      that comprise the respiratory chain and associated machinery for ATP synthesis.
      The work has culminated in advanced crystallographic and spectroscopic methods
      that provide structural and mechanistic details of this mitochondrial molecular
      machinery, in many instances to atomic level. I review here the current state of
      understanding of the mitochondrial respiratory chain in terms of structures and
      dynamics of the component proteins and their roles in the biological electron and
      proton transfer processes that result in ATP synthesis. These advances, together
      with emerging evidence of further diverse roles of mitochondria in health and
      disease, have prompted a new era of interest in mitochondrial function.

PMID- 14641006
TI  - Modular proteins at the cell surface.
AB  - Many proteins, including cell-surface receptors, extracellular matrix (ECM)
      proteins and intracellular signalling systems, are constructed from a relatively
      small number of domains or modules. Modularity provides biological systems with a
      convenient way of presenting binding sites on a stable protein scaffold, in the
      correct position for function; it also allows regulation by module rearrangement.
      Knowledge about modular proteins is increasing rapidly because of good databases
      and more systematic approaches to protein expression and structure determination.
      There have been a number of important recent structures of modular proteins at
      the cell surface, including the low-density-lipoprotein receptor, epidermal
      growth factor receptor and an integrin. These and other studies show how the main
      task of structural biology has moved from determination of module structures to
      the task of assessing how modular proteins are regulated and how they bind their
      various ligands. These aspects are illustrated here by recent studies of modular
      proteins carried out in our laboratory and elsewhere. Examples will include
      studies of ECM proteins, such as fibronectin, and proteins associated with focal
      adhesion complexes that involve fibronectin, integrins and various intracellular
      modular proteins, such as focal adhesion kinase, Src family kinases, talin and
      paxillin.

PMID- 14641007
TI  - The glucose-fatty acid cycle: a physiological perspective.
AB  - Glucose and fatty acids are the major fuels for mammalian metabolism and it is
      clearly essential that mechanisms exist for mutual co-ordination of their
      utilization. The glucose-fatty acid cycle, as it was proposed in 1963, describes
      one set of mechanisms by which carbohydrate and fat metabolism interact. Since
      that time, the importance of the glucose-fatty acid cycle has been confirmed
      repeatedly, in particular by elevation of plasma non-esterified fatty acid
      concentrations and demonstration of an impairment of glucose utilization. Since
      1963 further means have been elucidated by which glucose and fatty acids
      interact. These include stimulation of hepatic glucose output by fatty acids,
      potentiation of glucose-stimulated insulin secretion by fatty acids, and the
      cellular mechanism whereby high glucose and insulin concentrations inhibit fatty
      acid oxidation via malonyl-CoA regulation of carnitine palmitoyltransferase-1.
      The last of these mechanisms, discovered by Denis McGarry and Daniel Foster in
      1977, provides an almost exact complement to the mechanism described in the
      glucose-fatty acid cycle whereby high concentrations of fatty acids inhibit
      glucose utilization. These additional discoveries have not detracted from the
      important of the glucose-fatty acid cycle: rather, they have reinforced the
      importance of mechanisms whereby glucose and fat can interact.

PMID- 14641008
TI  - Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.
AB  - HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids
      from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes,
      catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated
      phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The
      anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels,
      accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL
      by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in
      primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in
      vitro activation as well as translocation from the cytosol to the lipid droplet,
      whereas the role of the third PKA site remains elusive. Adipocytes isolated from
      homozygous HSL-null mice, generated in our laboratory, exhibit completely blunted
      catecholamine-induced glycerol release and reduced fatty acid release, suggesting
      the presence of additional, although not necessarily hormone-activatable,
      triacylglycerol lipase(s). Basal hyperinsulinaemia, release of exaggerated
      amounts of insulin during glucose challenges and retarded glucose disposal during
      insulin tolerance tests suggest that HSL-null mice are insulin resistant. Liver,
      adipose tissue and skeletal muscle appear all to be sites of impaired insulin
      sensitivity in HSL-null mice.

PMID- 14641009
TI  - Fatty acid recycling in adipocytes: a role for glyceroneogenesis and
      phosphoenolpyruvate carboxykinase.
AB  - FA (fatty acid) recycling in adipose tissue appears to be an important pathway
      for regulating FA release into the blood during fasting. Re-esterification
      requires G3P (glycerol 3-phosphate), which cannot be synthesized from glucose
      because glycolysis is much reduced under such circumstances. In addition, G3P can
      scarcely originate from glycerol since glycerol kinase has a very low activity in
      white adipose tissue. It was shown about 35 years ago that a metabolic pathway
      named glyceroneogenesis, which allows G3P synthesis from non-carbohydrate
      precursors like pyruvate, lactate or amino acids, is activated during fasting.
      The major enzyme in this pathway was shown to be PEPCK-C [cytosolic
      phosphoenolpyruvate carboxykinase (GTP); EC 4.1.1.32]. The present review
      analyses the mechanisms by which a series of hormones and nutrients affect PEPCK
      C gene transcription and glyceroneogenesis and describes evidence for
      dysregulation of this pathway in type 2 diabetes.

PMID- 14641010
TI  - Roles of PPARdelta in the control of muscle development and metabolism.
AB  - PPARdelta (peroxisome proliferator-activated receptor delta)-specific agonists
      decrease plasma lipids and insulinaemia in obese animals. As skeletal muscle is
      one of the major organs for fatty acid catabolism, we have investigated the roles
      of the nuclear receptor in the control of muscle development and lipid
      metabolism, by using two approaches. We have used C(2)C(12) myotubes in which the
      PPARdelta activity was altered by overexpression of either native or dominant
      negative (DN) mutant forms of PPARdelta. Treatment of C(2)C(12) cells by specific
      PPARdelta agonists promotes expression of genes for proteins of fatty acid
      catabolism and increases fatty acid oxidation. These responses were increased in
      C(2)C(12)-PPARdelta cells and impaired in C(2)C(12)-PPARdeltaDN cells. We also
      constructed animal models with muscle-specific expression of PPARdelta (Cre/Lox
      approach). The effects of muscle-specific alteration of PPARdelta activity were
      studied on muscle development and metabolism as well as on body fat mass. These
      experiments indicated that PPARdelta plays a crucial role in myofibre typing
      determination and regulation of muscle oxidative capabilities, and that muscle
      specific overexpression of the nuclear receptor leads to reduction of adipocyte
      size and body fat mass. These data strongly suggest that PPARdelta controls fatty
      acid catabolism in muscle and that its activation by synthetic agonists could
      prevent or correct obesity and type 2 diabetes.

PMID- 14641011
TI  - Myocardial carnitine palmitoyltransferase I as a target for oxidative
      modification in inflammation and sepsis.
AB  - CPT I (outer membrane carnitine palmitoyltransferase I) is a crucial enzyme in
      myocardial substrate selection. Two isoforms exist in the heart, the liver (L-)
      and muscle (M-) isoforms, which have different kinetic characteristics and alter
      in relative amounts during the neonatal/weaning/adult transition. CPT I is a
      point for control and regulation of fatty acid oxidation via modulation of its
      activity by malonyl-CoA, the concentration of which is set by acetyl-CoA
      carboxylase, AMP-activated protein kinase and malonyl-CoA decarboxylase in
      response to, for example, alterations in glucose supply. Systemic inflammatory
      responses and sepsis lead to myocardial dysfunction as part of multiple system
      organ failure. We have shown that: (i) myocardial CPT I activity is inhibited
      during neonatal sepsis; (ii) on the basis of inhibitor studies this inhibition
      appears to be of M-CPT I rather than L-CPT I; (iii) nitration of M-CPT I occurs,
      probably by peroxynitrite, and this may be responsible for the decrease in CPT I
      activity; (iv) myocardial CPT I activity is also inhibited in another model of
      systemic inflammatory response, namely intestinal ischaemia/reperfusion injury,
      but this can prevented by whole-body moderate hypothermia. Inhibition of M-CPT I
      would be predicted to alter myocardial substrate selection but there are several
      questions that remain to be answered.

PMID- 14641012
TI  - Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with
      hyperinsulinism: a novel glucose-fatty acid cycle?
AB  - Hyperinsulinism of infancy is caused by inappropriate insulin secretion in
      pancreatic beta-cells, even when blood glucose is low. Several molecular defects
      are known to cause hyperinsulinism of infancy, such as K(ATP) channelopathies and
      regulatory defects of glucokinase and glutamate dehydrogenase. Although defects
      of fatty acid oxidation have not previously been known to cause hyperinsulinism,
      patients with deficiency in SCHAD (short-chain 3-hydroxyacyl-CoA dehydrogenase;
      an enzyme of mitochondrial beta-oxidation) have hyperinsulinism. A novel link
      between fatty acid oxidation and insulin secretion may explain hyperinsulinism in
      these patients.

PMID- 14641013
TI  - Mechanism of glucose sensing in the small intestine.
AB  - Sensing nutrients is a fundamental task for all living cells. For most eukaryotic
      cells glucose is a major source of energy, having significant and varied effects
      on cell function. Interest in identifying mechanisms by which cells sense and
      respond to variations in glucose concentration has increased recently. The
      epithelial cells lining the intestinal tract are exposed, from the luminal
      domain, to an environment with continuous and massive fluctuations in the levels
      of dietary monosaccharides. Enterocytes therefore have to sense and respond to
      the significant changes in the levels of luminal sugars, and regulate the
      expression of the intestinal glucose transporter (Na+/glucose co-transporter,
      SGLT1) accordingly. Our data, using a combination of in vivo and in vitro model
      systems, suggest that glucose in the lumen of the intestine is sensed by a
      glucose sensor residing on the external face of the enterocyte luminal membrane.
      Glucose binds to the sensor and generates an intracellular signal leading to
      enhancement in the expression of SGLT1. The generated signal is independent of
      glucose metabolism and is likely to operate via a G-protein-coupled receptor and
      cAMP/protein kinase A signalling cascade.

PMID- 14641014
TI  - Regulation of pyruvate dehydrogenase complex activity by reversible
      phosphorylation.
AB  - PDC (pyruvate dehydrogenase complex) catalyses the oxidative decarboxylation of
      pyruvate, linking glycolysis to the tricarboxylic acid cycle. Regulation of PDC
      determines and reflects substrate preference and is critical to the 'glucose
      fatty acid cycle', a concept of reciprocal regulation of lipid and glucose
      oxidation to maintain glucose homoeostasis developed by Philip Randle. Mammalian
      PDC activity is inactivated by phosphorylation by the PDKs (pyruvate
      dehydrogenase kinases). PDK inhibition by pyruvate facilitates PDC activation,
      favouring glucose oxidation and malonyl-CoA formation: the latter suppresses LCFA
      (long-chain fatty acid) oxidation. PDK activation by the high mitochondrial
      acetyl-CoA/CoA and NADH/NAD(+) concentration ratios that reflect high rates of
      LCFA oxidation causes blockade of glucose oxidation. Complementing glucose
      homoeostasis in health, fuel allostasis, i.e. adaptation to maintain
      homoeostasis, is an essential component of the response to chronic changes in
      glycaemia and lipidaemia in insulin resistance. We develop the concept that the
      PDKs act as tissue homoeostats and suggest that long-term modulation of
      expression of individual PDKs, particularly PDK4, is an essential component of
      allostasis to maintain homoeostasis. We also describe the intracellular signals
      that govern the expression of the various PDK isoforms, including the roles of
      the peroxisome proliferator-activated receptors and lipids, as effectors within
      the context of allostasis.

PMID- 14641015
TI  - Fatty acid-induced insulin resistance: role of insulin receptor substrate 1
      serine phosphorylation in the retroregulation of insulin signalling.
AB  - Insulin resistance, when combined with impaired insulin secretion, contributes to
      the development of type 2 diabetes. Insulin resistance is characterized by a
      decrease in the insulin effect on glucose transport in muscle and adipose tissue.
      Tyrosine phosphorylation of IRS-1 (insulin receptor substrate 1) and its binding
      to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin
      signalling cascade leading to insulin-stimulated glucose transport. Various
      studies have implicated lipids as a cause of insulin resistance in muscle.
      Elevated plasma fatty acid concentrations are associated with reduced insulin
      stimulated glucose transport activity as a consequence of altered insulin
      signalling through PI 3-kinase. Modification of IRS-1 by serine phosphorylation
      could be one of the mechanisms leading to a decrease in IRS-1 tyrosine
      phosphorylation, PI 3-kinase activity and glucose transport. Recent findings
      demonstrate that non-esterified fatty acids, as well as other factors such as
      tumour necrosis factor alpha, hyperinsulinaemia and cellular stress, increase the
      serine phosphorylation of IRS-1 and identified Ser(307) as one of the
      phosphorylated sites. Moreover, several kinases able to phosphorylate this serine
      residue have been identified. These exciting results suggest that Ser(307)
      phosphorylation is a possible hallmark of insulin resistance in biologically
      insulin-responsive cells or tissues. Identification of IRS-1 kinases could enable
      rational drug design in order to selectively inhibit the activity of the relevant
      enzymes and generate a novel class of therapeutic agents for type 2 diabetes.

PMID- 14641016
TI  - Bypassing the glucose/fatty acid cycle: AMP-activated protein kinase.
AB  - The AMPK (AMP-activated protein kinase) cascade plays a key role in regulating
      energy metabolism. Conditions which cause a decrease in the ATP/AMP ratio lead to
      activation of AMPK. Once activated, AMPK initiates a series of responses that act
      to restore the energy balance of the cell. In skeletal muscle, activation of AMPK
      increases both glucose uptake and fatty acid oxidation, raising the possibility
      that AMPK can bypass the glucose/fatty acid cycle. This review focuses on the
      role of AMPK in the regulation of glucose and fatty acid metabolism in muscle.
      Recently, naturally occurring mutations within the gamma isoforms have been
      identified which lead to altered metabolic regulation in cardiac and skeletal
      muscle and suggest an important role for the kinase in regulating glycogen
      metabolism.

PMID- 14641017
TI  - Extending the glucose/fatty acid cycle: a glucose/adipose tissue cycle.
AB  - It is now recognized that the WAT (white adipose tissue) produces a variety of
      bioactive peptides, collectively termed "adipokines". Alteration of WAT mass in
      obesity or lipoatrophy affects the production of most adipose secreted factors.
      Since both conditions are associated with insulin resistance, the idea has
      emerged that certain adipokines might influence insulin action. Among these,
      tumour necrosis factor alpha, interleukin-6 and resistin are increased in the
      obese state and interfere negatively with insulin-mediated processes. Conversely,
      leptin and adiponectin exert an insulin-sensitizing effect, at least in part by
      favouring tissue fatty-acid oxidation through AMP-activated kinase activation.
      Obesity-induced insulin resistance has been linked to leptin resistance and
      decreased plasma adiponectin, while administration of leptin and adiponectin
      normalizes plasma levels in lipoatrophic mice and reverses insulin resistance.
      Thiazolidinedione anti-diabetic agents increase endogenous adiponectin production
      in rodents and humans, supporting the idea that drugs targeting adipokines might
      represent a new therapeutic approach to sensitize peripheral tissues to insulin.

PMID- 14641018
TI  - AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates
      pyruvate dehydrogenase in vivo and improves blood glucose control in obese
      (fa/fa) Zucker rats.
AB  - PDH (pyruvate dehydrogenase) is a key enzyme controlling the rate of glucose
      oxidation, and the availability of gluconeogenic precursors. Activation of PDH in
      skeletal muscle and liver may increase glucose uptake and reduce glucose
      production. This study describes the properties of AZD7545, a novel, small
      molecule inhibitor of PDHK (PDH kinase). In the presence of PDHK2, AZD7545
      increased PDH activity with an EC(50) value of 5.2 nM. In rat hepatocytes, the
      rate of pyruvate oxidation was stimulated 2-fold (EC(50) 105 nM). A single dose
      of AZD7545 to Wistar rats increased the proportion of liver PDH in its active,
      dephosphorylated form in a dose-related manner from 24.7 to 70.3% at 30 mg/kg;
      and in skeletal muscle from 21.1 to 53.3%. A single dose of 10 mg/kg also
      significantly elevated muscle PDH activity in obese Zucker (fa/fa) rats. Obese,
      insulin-resistant, Zucker rats show elevated postprandial glucose levels compared
      with their lean counterparts (8.7 versus 6.1 mM at 12 weeks old). AZD7545 (10
      mg/kg) twice daily for 7 days markedly improved the 24-h glucose profile, by
      eliminating the postprandial elevation in blood glucose. These results suggest
      that PDHK inhibitors may be beneficial agents for improving glucose control in
      the treatment of type 2 diabetes.

PMID- 14641019
TI  - AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2.
AB  - The PDH (pyruvate dehydrogenase) multi-enzyme complex catalyses a key regulatory
      step in oxidative glycolysis. Phosphorylation of the E1 subunit of the complex on
      serine residues results in the inactivation of enzyme activity. A family of four
      dedicated PDH kinase isoenzymes exists, each of which displays a distinct tissue
      specific expression profile. AZD7545 is one of a series of PDH kinase inhibitors
      developed for the treatment of type 2 diabetes. The isoenzyme-selectivity profile
      of AZD7545 and related compounds is described and the consequences for their in
      vivo mode of action are discussed.

PMID- 14641020
TI  - VEGF signalling: integration and multi-tasking in endothelial cell biology.
AB  - The central role of VEGF (vascular endothelial growth factor A) in angiogenesis
      is dependent upon its ability to co-ordinately regulate multiple endothelial
      functions. The multifunctionality of VEGF at the cellular level results from its
      ability to initiate a diverse, complex and integrated network of signalling
      pathways via its major receptor, kinase-insert-domain-containing receptor (KDR).
      Activation of phospholipase C-gamma, protein kinase C, Ca(2+), ERK (extracellular
      signal-regulated protein kinase), Akt, Src, focal adhesion kinase and calcineurin
      pathways has been implicated in mediating multiple VEGF functions, including
      survival, proliferation, migration, vascular permeability, tubulogenesis, NO and
      prostanoid synthesis, and gene expression. NO and prostanoids in turn play
      paracrine and autocrine roles in linking post-receptor signalling to biological
      functions. Integration between biologically important signalling cascades occurs
      at several points. Akt and ERK, for example, are key junction points linking
      together signal transduction involved in survival and NO generation, and
      proliferation and prostanoid biosynthesis. Together, the multiplicity, functional
      versatility and integration of VEGF signalling provide a useful framework for
      understanding the mechanisms underlying the endothelial biological response to
      this key factor.

PMID- 14641021
TI  - Mechanisms controlling EGF receptor endocytosis and degradation.
AB  - Activated EGF (epidermal growth factor) receptors are removed from the cell
      surface via endocytosis and subsequent degradation in the lysosome. This
      ultimately attenuates EGF receptor signals and diminishes the level of cell
      activation. The mechanisms underlying the EGF receptor down-regulation are
      beginning to be elucidated at the molecular level. Recent reports have indicated
      that receptor monoubiquitination and networks of protein-protein interactions
      control distinct steps in EGF receptor internalization, endosomal trafficking and
      sorting for lysosomal degradation. The emerging importance of the ubiquitin
      ligase Cbl and the adaptor molecule CIN85 (Cbl-interacting protein of 85 kDa) in
      the regulation of these pathways is discussed in detail.

PMID- 14641022
TI  - The anti-apoptotic response of the Gq/11-coupled muscarinic receptor family.
AB  - It is now clear that G-protein-coupled receptors can regulate programmed cell
      death (apoptosis) through a variety of mechanisms that are dependent on cell type
      and receptor subtype. Here we present evidence that the G(q/11)-coupled subtypes
      of the muscarinic receptor family (namely M(1), M(3) and M(5)-muscarinic receptor
      subtypes) are able to protect against apoptotic cell death. In particular we
      demonstrate that the C-terminal tail of the M(3)-muscarinic receptor is an
      essential structural element for signalling to the anti-apoptotic pathway.
      Removal of the distal portion of the C-terminal tail results in a receptor that
      is coupled normally to the G(q/11)/phospholipase C pathway and the mitogen
      activated protein kinase pathway, but is unable to couple to the anti-apoptotic
      pathway. Furthermore, a poly-basic region conserved within the C-terminal tail of
      the G(q/11)-coupled muscarinic receptor subtypes appears to be the structural
      determinant of coupling to the anti-apoptotic pathway.

PMID- 14641023
TI  - The role of ERK2 docking and phosphorylation of PDE4 cAMP phosphodiesterase
      isoforms in mediating cross-talk between the cAMP and ERK signalling pathways.
AB  - PDE4 cAMP phosphodiesterases are widely expressed enzymes that serve as major
      regulators of cAMP signalling in cells. They provide targets for therapeutics
      having anti-inflammatory and cognitive-enhancing properties. ERK2 (extracellular
      signal-regulated kinase 2) interacts with the PDE4 catalytic unit by binding to a
      KIM (kinase interaction motif) docking site located on an exposed beta-hairpin
      loop and an FQF (Phe-Gln-Phe) specificity site located on an exposed alpha-helix.
      These flank a site that allows phosphorylation by ERK, the functional outcome of
      which is orchestrated by the N-terminal UCR1/2 (upstream conserved region 1 and
      2) modules. The three classes of PDE4 isoforms differ in these regulatory
      modules, allowing phosphorylation by ERK to lead to either inhibition or
      activation. ERK inhibition of long isoforms is regulated by a unique feedback
      control whereby elevated cAMP levels cause PKA (protein kinase A) to
      phosphorylate UCR1 and ablate the inhibitory action of ERK. PDE4 isoforms can
      also be found in complex with beta-arrestins where they provide a novel part of
      the cellular desensitization mechanism to receptor-mediated cAMP signalling.
      Stimulation of the beta(2)-adrenoceptor recruits beta-arrestins with bound PDE4,
      delivering an enzyme capable of degrading cAMP at its site of synthesis at the
      plasma membrane. Use of dominant negative PDE4 isoforms identifies that a major
      role of recruited PDE4 is to regulate plasma membrane PKA activity involved in
      phosphorylating the beta(2)-adrenoceptor. Recruited PDE4 thus desensitizes the
      ability of the beta(2)-adrenoceptor to activate ERK via G(i).

PMID- 14641024
TI  - Protease-activated receptor 2: activation, signalling and function.
AB  - PARs (protease-activated receptors) are a family of four G-protein-coupled
      receptors for proteases from the circulation, inflammatory cells and epithelial
      tissues. This report focuses on PAR(2), which plays an important role in
      inflammation and pain. Pancreatic (trypsin I and II) and extrapancreatic (trypsin
      IV) trypsins, mast cell tryptase and coagulation factors VIIa and Xa cleave and
      activate PAR(2). Proteases cleave PAR(2) to expose a tethered ligand that binds
      to the cleaved receptor. Despite this irreversible activation, PAR(2) signalling
      is attenuated by beta-arrestin-mediated desensitization and endocytosis, and by
      lysosomal targeting and degradation, which requires ubiquitination of PAR(2).
      beta-Arrestins also act as scaffolds for the assembly of multi-protein signalling
      complexes that determine the location and function of activated mitogen-activated
      protein kinases. Observations of PAR(2)-deficient mice support a role for PAR(2)
      in inflammation, and many of the effects of PAR(2) activators promote
      inflammation. Inflammation is mediated in part by activation of PAR(2) in the
      peripheral nervous system, which results in neurogenic inflammation and
      hyperalgesia.

PMID- 14641025
TI  - Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation
      and vascular remodelling.
AB  - AngII (angiotensin II) and its G-protein-coupled AT(1) receptor play critical
      roles in mediating cardiovascular diseases such as hypertension, atherosclerosis
      and restenosis after vascular injury. It is widely believed that AngII promotes
      these diseases by inducing vascular remodelling that involves hypertrophy,
      hyperplasia and migration of VSMCs (vascular smooth muscle cells). We have shown
      that transactivation of an ErbB family receptor, EGFR (epidermal growth factor
      receptor; ErbB1), is essential for VSMC hypertrophy and migration induced by
      AngII. However, the precise signal transduction mechanism by which AngII
      transactivates EGFR/ErbB1 and whether other ErbBs are also required for AngII
      function remains unclear. Recent studies suggest an involvement of a
      metalloprotease-dependent ErbB family ligand production in the transactivation.
      Here, we will discuss the roles and mechanisms of AngII/AT(1) receptor in
      promoting ErbB receptors transactivation in VSMCs. Further elucidation of this
      ErbB activation machinery not only will give us a better understanding of the
      critical molecular mechanism underlying vascular remodelling stimulated by AngII,
      but will also contribute to development of novel treatment strategies for
      cardiovascular diseases.

PMID- 14641026
TI  - EGFR signal transactivation in cancer cells.
AB  - The EGFR (epidermal growth factor receptor) plays a key role in the regulation of
      essential normal cellular processes and in the pathophysiology of
      hyperproliferative diseases such as cancer. Recent investigations have
      demonstrated that GPCRs (G-protein-coupled receptors) are able to utilize the
      EGFR as a downstream signalling partner in the generation of mitogenic signals.
      This cross-talk mechanism combines the broad diversity of GPCRs with the
      signalling capacities of the EGFR and has emerged as a general concept in a
      multitude of cell types. The molecular mechanisms of EGFR signal transactivation
      involve processing of transmembrane growth factor precursors by metalloproteases
      which have been recently identified as members of the ADAM (a disintegrin and
      metalloprotease) family of zinc-dependent proteases. Subsequently, the EGFR
      transmits signals to prominent downstream pathways, such as mitogen-activated
      protein kinases, the phosphoinositide 3-kinase/Akt pathway and modulation of ion
      channels. Analysis of GPCR-induced EGFR activation in more than 60 human
      carcinoma cell lines derived from different tissues has demonstrated the broad
      relevance of this signalling mechanism in cancer. Moreover, EGFR signal
      transactivation was linked to diverse biological processes in human cancer cells,
      such as cell proliferation, migration and anti-apoptosis. Together with
      investigations revealing the importance of this GPCR-EGFR cross-talk mechanism in
      cardiac hypertrophy, Helicobacter pylori -induced pathophysiological processes
      and cystic fibrosis, these findings support an important role for GPCR ligand
      dependent EGFR signal transactivation in diverse pathophysiological disorders.

PMID- 14641027
TI  - Lysophosphatidic acid: mitogen and motility factor.
AB  - LPA (lysophosphatidic acid), the simplest of al glycerophospholipids, is a potent
      inducer of cell proliferation, migration and survival. It does so by activating
      its cognate G-protein-coupled receptors, four of which have been identified. LPA
      receptors couple to at least three distinct G-proteins and thereby activate
      multiple signal transduction pathways, particularly those initiated by the small
      GTPases Ras, Rho and Rac. Our recent work has shown that LPA signals Rac
      activation via the Tiam1 GDP/GTP exchange factor and thereby stimulates cell
      migration. Here we discuss recent progress in our understanding of LPA action.

PMID- 14641028
TI  - Stress-induced ATP release from and growth modulation of human lens and retinal
      pigment epithelial cells.
AB  - ATP release has been shown to occur following stimulation in several cellular
      systems. This study was undertaken to determine if lens and retinal epithelial
      cells release ATP in response to physiological stresses and to elucidate a
      possible role for ATP. Analysis of human aqueous humour samples showed a mean ATP
      level of 37.8+/-7.7 nM. Hyper-osmotic stress induced a dose- and time-dependent
      release of ATP. Both cell types were found to proliferate in serum-free medium,
      and the addition of ATP and adenosine at concentrations as low as 0.1 nM
      inhibited growth. Gene profiling also demonstrated the presence of the
      ectonucleotidases CD39 and CD73 and the A1 adenosine receptor on both cell types.

PMID- 14641029
TI  - Exogenous and intracellularly generated sphingosine 1-phosphate can regulate
      cellular processes by divergent pathways.
AB  - S1P (sphingosine 1-phosphate) is the ligand for a family of specific G-protein
      coupled receptors that regulate a wide variety of important cellular functions,
      including vascular maturation, angiogenesis, cell growth, survival, cytoskeletal
      rearrangements and cell motility. However, S1P also may have intracellular
      functions. In this review, we discuss two examples that clearly indicate that
      intracellularly generated and exogenous S1P can regulate biological processes by
      divergent pathways.

PMID- 14641030
TI  - Receptor tyrosine kinase-GPCR signal complexes.
AB  - The formation of complexes between growth factor receptors and members of a
      family of G-protein-coupled receptors whose natural ligands are S1P (sphingosine
      1-phosphate) and LPA (lysophosphatidic acid) represents a new signalling entity.
      This receptor complex allows for integrated signalling in response to growth
      factor and/or S1P/LPA and provides a mechanism for more efficient activation (due
      to integrated close-proximity signalling from both receptor classes) of the
      p42/p44 MAPK (mitogen-activated protein kinase) pathway. This article provides
      information on the molecular events at the interface between receptor tyrosine
      kinases and S1P/LPA receptors. Examples include the PDGF (platelet-derived growth
      factor)-induced tyrosine phosphorylation of G(i)alpha, released upon S1P(1)
      receptor activation, which is required for initiation of the p42/p44 MAPK
      pathway. Critical to this event is the formation of endocytic vesicles containing
      functionally active PDGFbeta receptor-S1P(1) receptor complexes, which are
      internalized and relocated with components of the p42/p44 MAPK pathway. We also
      report examples of cross-talk signal integration between the Trk A (tropomyosin
      receptor kinase A) receptor and the LPA(1) receptor in terms of the NGF (nerve
      growth factor)-dependent regulation of the p42/p44 MAPK pathway. NGF induces
      recruitment of the LPA(1) receptor to the nucleus (delivery might be Trk A
      dependent), whereupon the LPA(1) receptor may govern gene expression via novel
      nuclear signalling processes.

PMID- 14641031
TI  - Maintaining the permeability barrier during protein trafficking at the
      endoplasmic reticulum membrane.
AB  - Many proteins are translocated across or integrated into a cellular membrane
      without disrupting its integrity, although it is difficult to imagine how such
      macromolecular transmembrane movement can occur without simultaneously allowing
      significant small-molecule and ion diffusion across the bilayer. Recent studies
      have identified some molecular mechanisms that are involved in maintaining the
      permeability barrier of the endoplasmic reticulum membrane during co
      translational protein translocation and integration. These mechanisms are both
      simple and direct in concept, but are operationally complex and require the co
      ordinated and regulated interaction of several multicomponent complexes.

PMID- 14641032
TI  - Getting to the membrane: how is co-translational protein targeting to the
      endoplasmic reticulum regulated?
AB  - Co-translational protein targeting to the endoplasmic reticulum requires the
      signal-recognition particle, its cognate receptor and the translocation channel.
      Co-ordination of the targeting process necessitates the interaction of these
      components with each other and with the ribosome. These interactions are
      regulated by three GTPases, which act in concert, ensuring the fidelity of the
      targeting process.

PMID- 14641033
TI  - Biogenesis of tail-anchored proteins.
AB  - A group of integral membrane proteins, known as C-tail anchored, is defined by
      the presence of a cytosolic N-terminal domain that is anchored to the
      phospholipid bilayer by a single segment of hydrophobic amino acids close to the
      C-terminus. The mode of insertion into membranes of these proteins, many of which
      play key roles in fundamental intracellular processes, is obligatorily post
      translational, is highly specific and may be subject to regulatory processes that
      modulate the protein's function. Recent work has demonstrated that tail-anchored
      proteins translocate their C-termini across the endoplasmic reticulum membrane by
      a mechanism different from that used for Sec61-dependent post-translational
      signal-peptide-driven translocation. Here we summarize recent results on the
      insertion of tail-anchored proteins and discuss possible mechanisms that could be
      involved.

PMID- 14641034
TI  - Intramembrane proteolysis and post-targeting functions of signal peptides.
AB  - Signal sequences are the addresses of proteins destined for secretion. In
      eukaryotic cells, they mediate targeting to the endoplasmic reticulum membrane
      and insertion into the translocon. Thereafter, signal sequences are cleaved from
      the pre-protein and liberated into the endoplasmic reticulum membrane. We have
      recently reported that some liberated signal peptides are further processed by
      the intramembrane-cleaving aspartic protease signal peptide peptidase. Cleavage
      in the membrane-spanning portion of the signal peptide promotes the release of
      signal peptide fragments from the lipid bilayer. Typical processes that include
      intramembrane proteolysis is the regulatory or signalling function of cleavage
      products. Likewise, signal peptide fragments liberated upon intramembrane
      cleavage may promote such post-targeting functions in the cell.

PMID- 14641035
TI  - Making membrane proteins at the mammalian endoplasmic reticulum.
AB  - Whereas protein biogenesis at the endoplasmic reticulum is well understood in the
      case of secretory proteins and simple membrane proteins, much less is known about
      the synthesis of multi-spanning integral membrane proteins. While it is clear
      that the multiple membrane-spanning domains of these proteins must be inserted
      into the lipid bilayer during biosynthesis, the mechanism by which their
      integration is achieved and their subsequent folding/assembly are poorly defined.
      In this review, we summarize our current understanding of protein synthesis at
      the endoplasmic reticulum and highlight specific features that are relevant to
      the biogenesis of multi-spanning membrane proteins.

PMID- 14641036
TI  - Organization of translocon complexes in ER membranes.
AB  - Protein translocation in the ER (endoplasmic reticulum) and N-glycosylation are
      fundamental processes essential for the normal functioning of eukaryotic cells.
      They are the initial steps in the intracellular pathway that are followed by
      secretory proteins and membrane proteins of the endomembrane system and the
      plasma membrane. The translocation and concurrent N-glycosylation of these
      proteins take place on a large molecular machine, the TC (translocon complex),
      which is associated with membrane-bound polysomes. Segregation of TCs into a
      differentiated domain of the ER, the rough ER, may increase the efficiency of
      protein synthesis on membrane-bound polysomes. Our research is concerned with the
      assembly, functional organization and dynamics of the TCs in the ER, and their
      contribution to the functioning and the morphological appearance of this
      organelle. We hypothesize that the TCs form higher-order structures defining the
      rough domain of the ER. These structures, which are immobilized or diffuse slowly
      in the plain of the ER membrane, may be formed and stabilized by mRNAs
      interconnecting the TCs, by cytoskeletal elements and/or by hypothetical proteins
      that form links between the TCs. We have established the M3/18 cell line, which
      expresses the GFP (green fluorescent protein)-Dad1 fusion protein quantitatively
      and functionally incorporated into the OST (oligosaccharyltransferase). GFP-Dad1
      can be used as a reporter molecule for the lateral mobility of the TCs since the
      OST is tightly associated with the complex. As determined by FRAP (fluorescence
      recovery after photobleaching), the lateral mobility of GFP-Dad1-tagged TCs was
      much more restricted than expected from the estimated size of the TC and can be
      affected by the functional state of the TCs. Currently, we are studying the
      possible involvement of cytoskeletal elements in the organization of the TCs. Our
      data suggest that microtubules also play a role in the immobilization of the TCs.

PMID- 14641037
TI  - How does the translocon differentiate between hydrophobic sequences that form
      part of either a GPI (glycosylphosphatidylinositol)-anchor signal or a stop
      transfer sequence?
AB  - Newly synthesized proteins entering the eukaryotic secretory pathway may be
      attached to the lipid membrane by essentially one of two mechanisms. They may
      either contain a hydrophobic stop transfer sequence that directs their
      integration into the bilayer with the consequence that the polypeptide spans the
      membrane either one or several times, or alternatively the polypeptide chain may
      be modified by the covalent addition of a lipid anchor resulting in the
      attachment of the protein to the membrane via the lipid moiety. The major pathway
      for the covalent addition of a lipid anchor involves the post-translational
      attachment of GPI (glycosylphosphatidylinositol) to the C-terminus. Proteins
      modified in this way contain a specific signal that is recognized by the GPI
      anchor processing machinery. Hence both the integration of protein directly into
      the lipid bilayer and the addition of GPI anchors require the presence of
      sequences within the polypeptide chain to target the proteins to these pathways.
      This article will describe the main characteristics of these signals and their
      similarities and will discuss how the translocon may play a crucial role in their
      recognition.

PMID- 14641038
TI  - Retrograde transport of toxins across the endoplasmic reticulum membrane.
AB  - Several protein toxins, including the A chain of the plant protein ricin (RTA),
      enter mammalian cells by endocytosis and catalytically modify cellular components
      to disrupt essential cellular processes. In the case of ricin, the process
      inhibited is protein synthesis. In order to reach their cytosolic substrates,
      several toxins undergo retrograde transport to the ER (endoplasmic reticulum)
      before translocating across the ER membrane. To achieve this export, these toxins
      exploit the ERAD (ER-associated protein degradation) pathway but must escape, at
      least in part, the normal degradative fate of ERAD substrates in order to
      intoxicate the cell. Toxins that translocate from the ER have an unusually low
      lysine content that reduces the likelihood of ubiquitination and ubiquitin
      mediated proteasomal degradation. We have changed the two lysyl residues normally
      present in RTA to arginyl residues. Their replacement in RTA did not have a
      significant stabilizing effect on the protein, suggesting that the endogenous
      lysyl residues are not sites for ubiquitin attachment. However, when four
      additional lysyl residues were introduced into RTA in a way that did not
      compromise the activity, structure or stability of the toxin, degradation was
      significantly enhanced. Enhanced degradation resulted from ubiquitination that
      predisposed the toxin to proteasomal degradation. Treatment with the proteasomal
      inhibitor lactacystin increased the cytotoxicity of the lysine-enriched RTA to a
      level approaching that of wild-type RTA.

PMID- 14641039
TI  - Experiment and computer-aided simulation: complementary tools to understand
      exercise metabolism.
AB  - During the last two decades the concept of the MLSS (maximal lactate steady
      state) has been established. The MLSS detects the highest level of the BLC (blood
      lactate concentration) and the corresponding workload (MLSS workload) that can be
      maintained over time without continual BLC accumulation. In spite of a lack of
      experimental and/or theoretical foundation, it has been speculated that the level
      of the MLSS may decrease with increasing performance capacity. The potential
      inter-relationship between performance capacity and BLC response to prolonged
      constant workload will be analysed based on a recent study, which provided
      evidence that the MLSS is independent of performance whereas MLSS workload
      increases with performance capacity, and by a computer-aided simulation. The
      simulated model modifies and combines previous theories put forward to explain
      the response of BLC to exercise and incorporates a theory about limiting factors
      of oxygen transport to the muscle cell. Simulations consider the BLC response to
      selected prolonged constant workloads while paying special respect to changes in
      body structure and substrate utilization, which are generally accepted as
      limiting factors of performance capacity. This complex modulation of appearance
      and disappearance of lactate during constant prolonged exercise seems to support
      the experimental results, which indicated independence between MLSS and
      performance capacity.

PMID- 14641040
TI  - Nutritional status, metabolic responses to exercise and implications for
      performance.
AB  - Diet can significantly influence exercise performance. Diet alone will not ensure
      successful performance in sport, but it plays a permissive role in allowing
      sustained intensive training with limited risk of illness and injury. Diet may
      also promote adaptations to training by stimulating synthesis and breakdown of
      the specific proteins that respond to the training stimulus. Protein synthesis
      and breakdown are both stimulated for some time after exercise, and protein
      ingestion before, during or immediately after exercise will enhance the
      fractional synthetic rate. Carbohydrate and fat are key energy substrates during
      exercise, and acute nutritional manipulation will affect both substrate selection
      and exercise performance.

PMID- 14641041
TI  - Modulation of carbohydrate and fat utilization by diet, exercise and environment.
AB  - At rest and during exercise carbohydrate and fat are the predominant substrates.
      They are oxidized simultaneously but the relative contribution of these two
      substrates is dependent on a variety of factors including the exercise intensity
      and duration, diet, environmental conditions and training status. Changes in
      carbohydrate metabolism during the transition from rest to exercise and from low-
      to high-intensity exercise are mainly due to allosteric regulation. The factors
      that up-regulate fat metabolism in the transition to moderate-intensity exercise
      and the factors that result in a down-regulation of fat metabolism at higher
      intensities are incompletely understood. Substrate use is further modulated by
      the endocrine milieu (e.g. catecholamines, insulin, cortisol) and possibly
      cytokines (e.g. interleukin-6). With increasing duration of exercise there are
      marked increases in fat metabolism and decreases in carbohydrate metabolism and
      this has been ascribed mainly to substrate availability. Both acute food intake
      and chronic diets also have profound effects on substrate utilization. An
      increase in carbohydrate intake will rapidly suppress fat metabolism and increase
      carbohydrate metabolism whereas such an adaptation to a high-fat diet may take
      several days. The environmental conditions can also alter substrate use; high
      ambient temperatures can increase glycogen breakdown as a result of increased
      body core temperature and increased circulation catecholamines. Low temperatures
      can also increase carbohydrate metabolism, especially when shivering. In addition
      to these factors adaptation to training, in particular endurance training, will
      reduce the reliance on carbohydrate metabolism and increase fat oxidation,
      especially from intramuscular triacylglycerol stores.

PMID- 14641042
TI  - Regulation of PDH activity and isoform expression: diet and exercise.
AB  - During exercise in human skeletal muscle, the proportion of carbohydrate derived
      acetyl-CoA is determined at least in part by the activity of the PDH (pyruvate
      dehydrogenase) complex. Inhibition of the complex is achieved through reversible
      phosphorylation of the E1 subunit by a family of PDH kinase isoforms (PDK1-4)
      while dephosphorylation and activation of the complex is catalysed by a pair of
      intrinsic PDH phosphatases (PDP1 and 2). In general, the relative activity of the
      kinases and phosphatases is determined by a host of intramitochondrial effectors
      which signal energy charge, substrate and product accumulation, muscle
      contraction and nutritional status. This review focuses on advances in our
      understanding in human skeletal muscle of the regulatory signals and changes in
      gene expression which are important during acute exercise and exercise training,
      as well as in prolonged situations of altered nutritional status.

PMID- 14641043
TI  - Insulin signalling, exercise and cellular integrity.
AB  - Although the effects of exercise on insulin sensitivity are generally positive,
      eccentric exercise presents a paradox because it induces a transient state of
      insulin resistance that persists for up to 48 h after the exercise bout.
      Excessive eccentric contractions, such as prolonged downhill running, or marathon
      running, causes muscle damage and disruption of the integrity of the cell. Down
      regulation of insulin receptor tyrosine phosphorylation and subsequent steps in
      the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)
      associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation
      and activity and glucose transporter (GLUT-4) protein content, are evident in
      skeletal muscle after eccentric exercise. Furthermore, increased tumour necrosis
      factor alpha (TNF-alpha) secretion from monocytes is associated with the decrease
      in PI3K activity after this type of exercise. Recent studies have shown that TNF
      alpha can increase IRS-1 serine/threonine phosphorylation, which impairs IRS-1
      docking to the insulin receptor, and this inhibits insulin signalling. Thus a
      unifying hypothesis to explain insulin resistance after eccentric exercise may
      include inflammation arising from the disruption of muscle-cell integrity,
      leading to an acute-phase response that includes TNF-alpha, with the latter
      inhibiting insulin signalling and subsequent metabolic events. In contrast,
      exercise training increases insulin signalling and GLUT-4 expression, decreases
      TNF-alpha expression in skeletal muscle, and is associated with enhanced insulin
      sensitivity. These observations highlight the complexity of the cellular and
      molecular adaptations to exercise. Understanding these adaptations is essential
      in order to establish a sound theoretical basis for recommending exercise as a
      therapeutic intervention for insulin resistance and type 2 diabetes.

PMID- 14641044
TI  - The renin-angiotensin system and physical performance.
AB  - Many of us recognize that some individuals seem "gifted" in sporting ability. We
      may also have noted the association of such elite performance with past parental
      success, recognizing intuitively the role of inherited traits. With the expansion
      of molecular biology and associated technologies, we now find ourselves better
      able to explore these genetic influences. This article examines the role of the
      renin-angiotensin system in regulating physical performance, based on data
      arising from candidate gene-association studies. In particular, the association
      of angiotensin-converting enzyme genotype with performance-related phenotypes
      will be addressed. Finally, we will briefly discuss the applicability of this
      data to disease states such as heart failure.

PMID- 14641045
TI  - Transgenic models--a scientific tool to understand exercise-induced metabolism:
      the regulatory role of AMPK (5'-AMP-activated protein kinase) in glucose
      transport and glycogen synthase activity in skeletal muscle.
AB  - The AMPK (5'AMP-activated protein kinase) is becoming recognized as a critical
      regulator of energy metabolism. However, many of these effects in muscle
      metabolism have been ascribed to AMPK based on the use of the unspecific
      activator AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside). Using
      mouse models in which AMPK activity has been specifically blocked (kinase dead)
      or knocked out we and others have been able to conduct studies gaining more
      conclusive data on the role of AMPK in muscle metabolism. In this mini-review
      focus is on AMPK and its regulatory role for glucose transport and GS (glycogen
      synthase) activity in skeletal muscle, indicating that AMPK is a GS kinase in
      vivo which might influence GS activity during exercise and that AMPK is involved
      in AICAR/hypoxia-induced glucose transport but not or only partially in
      contraction-stimulated glucose transport.

PMID- 14641046
TI  - Using mitochondria-targeted molecules to study mitochondrial radical production
      and its consequences.
AB  - The production of ROS (reactive oxygen species) by the mitochondrial respiratory
      chain contributes to a range of pathologies, including neurodegenerative
      diseases, ischaemia/reperfusion injury and aging. There are also indications that
      mitochondrial ROS production plays a role in damage response and signal
      transduction pathways. To unravel the role of mitochondrial ROS production in
      these processes, we have developed a range of mitochondria-targeted probe
      molecules. Covalent attachment of a lipophilic cation leads to their accumulation
      into mitochondria, driven by the membrane potential. Molecules developed so far
      include antioxidants designed to intercept mitochondrial ROS and reagents that
      specifically label mitochondrial thiol proteins. Here we outline how
      mitochondrial ROS formation and its consequences can be investigated using these
      probes.

PMID- 14641047
TI  - Mitochondrial matrix reactive oxygen species production is very sensitive to mild
      uncoupling.
AB  - Mitochondria produce ROS (reactive oxygen species) as a by-product of aerobic
      respiration. Several studies in mammals and birds suggest that the most
      physiologically relevant ROS production is from complex I following reverse
      electron flow, and is highly sensitive to membrane potential. A study of
      Drosophila mitochondria respiring glycerol 3-phosphate revealed that membrane
      potential-sensitive ROS production from complex I following reverse electron flow
      was on the matrix side of the inner membrane. A 10 mV decrease in membrane
      potential was enough to abolish around 70% of the ROS produced by complex I under
      these conditions. Another important ROS generator in this model, glycerol-3
      phosphate dehydrogenase, produced ROS mostly to the cytosolic side; this ROS
      production was totally insensitive to a small decrease in membrane potential (10
      mV). Thus mild uncoupling may be particularly significant for ROS production from
      complex I on the matrix side of the mitochondrial inner membrane.

PMID- 14641048
TI  - Novel peptoids for the detection and suppression of reactive oxygen and nitrogen
      species.
AB  - Novel peptoids useful for the detection and suppression of various components
      contributing to oxidative stress and for elucidation of the interplay between
      these species are presented. Oxidative stress involves redox-active metal ion
      activation/generation of RONS (reactive oxygen and nitrogen species). For
      detection of RONS, the peptoid probes consist of a conjugate designed to (1)
      complex redox-active and non-redox-active metal ions, and (2) differentiate
      between RONS based upon the reaction products following RONS attack on the probe.
      For suppression of RONS, subtle modifications in peptoid structure impart
      catalase and superoxide dismutase activities to the peptoids upon ferric or
      cupric ion complexation.

PMID- 14641049
TI  - Oxidative stress and aging--the use of superoxide dismutase/catalase mimetics to
      extend lifespan.
AB  - To date, more than 40 genes have been identified in the nematode Caenorhabditis
      elegans, which, when mutated, lead to an increase in lifespan. Of those tested,
      all confer an increased resistance to oxidative stress. In addition, the lifespan
      of C. elegans can also be extended by the administration of synthetic superoxide
      dismutase/catalase mimetics. These compounds also appear to confer resistance to
      oxidative damage, since they protect against paraquat treatment. The protective
      effects of these compounds are apparent with treatment during either development
      or adulthood. These findings have demonstrated that pharmacological intervention
      in the aging process is possible and that these compounds can provide important
      information about the underlying mechanisms. To date, such interventions have
      targeted known processes rather than screening compound libraries because of the
      limitations of assessing lifespan in nematodes. However, we have recently
      developed a microplate-based assay that allows for a rapid and objective score of
      nematode survival at rates many times higher than previously possible. This
      system now provides the opportunity to perform high-throughput screens for
      compounds that affect nematode survival in the face of acute oxidative stress and
      will facilitate the identification of novel drugs that extend nematode lifespan.

PMID- 14641050
TI  - Cell respiration and formation of reactive oxygen species: facts and artefacts.
AB  - It is generally taken as an established fact that mitochondrial respiration is
      associated with the generation of small amounts of ROS (reactive oxygen species).
      There are many arguments supporting this side activity. A major argument is the
      particular physico-chemical configuration of dioxygen, which prevents the
      transfer of a pair of electrons. Instead, oxygen is reduced by the successive
      transfer of single electrons, necessarily leading to intermediates with odd
      electrons. The high rate of turnover of oxygen in the respiratory chain in
      combination with the existence of single-electron carriers supports the concept
      of mitochondria as the major cellular ROS generator. Experimental evidence on the
      ability of mitochondria to generate ROS was, however, based essentially on in
      vitro experiments with isolated mitochondria. A variety of structural and
      functional alterations associated with the removal of mitochondria from the cell,
      as well as the routinely applied ROS detection methods, may lead to artefactual
      deviation of odd electrons to dioxygen. We therefore checked these correlations
      in view of ROS formation, including the often reported effect of the membrane
      potential on the establishment of a redox couple with oxygen out of sequence. For
      this purpose we developed novel methods to prove the authenticity of mitochondria
      for ROS generation in the living cell. Based on our experiments, we can exclude
      spontaneous release of ROS from mitochondria. However, we describe conditions
      under which mitochondria can be transformed to mild ROS generators. The site of
      single-electron deviation to dioxygen was found to be ubiquinol interacting with
      the Rieske iron-sulphur protein and low-potential cytochrome b of the bc (1)
      complex.

PMID- 14641051
TI  - Cytochrome c, an ideal antioxidant.
AB  - Generation of DeltaPsi (membrane potential) by cytochrome oxidase proteoliposomes
      oxidizing superoxide-reduced cytochrome c has been demonstrated. XO+HX (xanthine
      oxidase and hypoxanthine) were used to produce superoxide. It was found that the
      generation of DeltaPsi is completely abolished by cyanide (an uncoupler) or by
      superoxide dismutase, and is enhanced by nigericin. Addition of ascorbate after
      XO+HX causes a further increase in DeltaPsi. On the other hand, XO+HX added after
      ascorbate do not affect DeltaPsi, indicating that superoxide does not have
      measurable protonophorous activity. The half-maximal cytochrome c concentration
      for DeltaPsi generation supported by XO+HX was found to be approx. 1 microM.
      These data and the results of some other researchers can be rationalized as
      follows: (1) O(2) accepts an electron to form superoxide; (2) cytochrome c
      oxidizes superoxide back to O(2); (3) an electron removed from the reduced
      cytochrome c is transferred to O(2) by cytochrome oxidase in a manner that
      generates Deltamicro(H(+)) (transmembrane difference in electrochemical H(+)
      potential). Thus cytochrome c mediates a process of superoxide removal, resulting
      in regeneration of O(2) and utilization of the electron involved previously in
      the O(2) reduction. It is important that cytochrome c is not damaged during the
      antioxidant reaction, in contrast with many other antioxidants.

PMID- 14641052
TI  - Possible role of free oxidation processes in the regulation of reactive oxygen
      species production in plant mitochondria.
AB  - The non-coupled substrate oxidation mediated by components of the electron
      transport chain that are not coupled to energy accumulation (such as plant
      alternative oxidase and rotenone-insensitive NADH dehydrogenases) and uncoupled
      respiration are peculiar features of plant mitochondria. The physiological
      significance of such energy-wasting oxidation processes is still debated. It is
      proposed that non-coupled oxidation could regulate the level of reduction of
      components of the electron transport chain and the rate of one-electron reduction
      of oxygen, thereby affecting the rate of formation of reactive oxygen species.

PMID- 14641053
TI  - The irony of manganese superoxide dismutase.
AB  - The manganese and iron SODs (superoxide dismutases) form a superfamily of closely
      related antioxidant defence metalloenzymes. MnSOD requires Mn (not Fe) for
      activity. However, when MnSOD is expressed in Escherichia coli grown in medium
      supplemented with ferrous salts, Fe substitutes for Mn in the active site,
      reflecting relatively indiscriminate uptake of either Mn or Fe and a surprisingly
      low selectivity for the identity of the bound metal ion. X-ray crystallographic
      studies on Fe-substituted MnSOD show that the substrate access channel is blocked
      by solvent (hydroxide), providing a structural explanation for the observed metal
      specificity of the catalytic activity. The mechanism of metal binding has been
      investigated in vitro using recombinant thermophilic SODs. The thermophilic
      Thermus thermophilus MnSOD expressed in E. coli was isolated as the metal-free
      apoprotein when heat treatment was eliminated from the purification procedure.
      While incubation of the purified MnSOD apoprotein with metal salts at ambient
      temperatures did not restore SOD activity, re-activation could be achieved by
      heating the protein with Mn salts at elevated temperatures. This in vitro
      thermally triggered metal uptake is non-specific for the metal ion; both Mn and
      Fe bind, but only Mn restores catalytic activity. Formation of the metal complex
      is essentially irreversible under these conditions. The metallation process is
      strongly temperature-dependent, suggesting that there are substantial activation
      barriers to metal uptake at ambient temperatures that are overcome by a
      transition in the apoprotein structure under physiological conditions. Two
      mechanisms may be proposed for SOD metallation: one involving subunit
      dissociation and another involving domain separation. Thermally triggered metal
      binding by thermophilic SODs is providing new insight into the metallation
      mechanism of the SOD apoprotein, which is likely to be conserved over this family
      of enzymes.

PMID- 14641054
TI  - Prokaryotic Cu,Zn superoxide dismutases.
AB  - The Cu,ZnSODs (Cu,Zn superoxide dismutases) comprise a class of ubiquitous
      metalloenzymes that catalyse the dismutation of the superoxide radical anion into
      oxygen and hydrogen peroxide. The dismutation reaction involves two successive
      encounters of the superoxide anion with a catalytic copper centre hosted by the
      enzyme at the dead end of a narrow protein channel. Cu,ZnSOD is found in all
      eukaryotic species as a homodimeric enzyme of approx. 2x16 kDa. Cu,ZnSODs are
      also widely distributed in the prokaryotic phyla, and are found in the
      periplasmic space of bacterial pathogens, where they are likely to play a
      defensive role against extracellular oxidative stress, particularly with respect
      to phagocytic processes. The crystallographic structures of prokaryotic Cu,ZnSODs
      have shown that the core structural organization of the enzyme is based on a
      flattened antiparallel beta-barrel, composed of eight strands arranged in a Greek
      key topological order, which usually forms a dimeric structure through the
      interaction of residues provided by beta-strands 4f and 5e with the 2,3 and 7,8
      loops. The interface residues are arranged to form a closed ring, which surrounds
      a central cavity filled by water molecules that are arranged differently
      depending on the species. The interface variability of residues and solvent
      structure observed in bacterial enzymes permits fine tuning of the subunit
      association that results in the presence of monomeric and dimeric species, and
      confers a particular protein flexibility that gives rise to long-range
      communications between different region of the enzyme.

PMID- 14641056
TI  - Iron superoxide dismutases: structure and function of an archaic enzyme.
AB  - Iron and manganese superoxide dismutases are phylogenetically closely related.
      They are compared by in silico analysis with regard to their metal specificity
      and their three-dimensional structure. Special attention is given to the
      structure and properties of superoxide dismutases from archaeal prokaryotes. The
      mechanism and the extreme thermostability of superoxide dismutase from Sulfolobus
      acidocaldarius are discussed on the basis of its high-resolution X-ray structure.
      An alternating-site mechanism and an evolutionary origin of superoxide dismutases
      under the environmental conditions on the early Earth are proposed.

PMID- 14641055
TI  - Role of prokaryotic Cu,Zn superoxide dismutase in pathogenesis.
AB  - Several bacterial pathogens possess sodC genes that encode periplasmic or
      membrane-associated Cu,Zn superoxide dismutases. Since professional phagocytes
      generate large amounts of reactive oxygen species to control the growth of
      invading micro-organisms, Cu,Zn superoxide dismutase might protect infectious
      bacteria from oxy-radical damage and facilitate their survival within the host.
      This idea has gained support from studies showing that sodC -null mutants of
      different bacteria are less virulent than their parental wild-type strains, and
      from the discovery that, despite apparent dispensability for growth under
      laboratory conditions, various pathogens (including several highly virulent
      Salmonella strains) possess multiple copies of sodC. Our studies indicate that
      Cu,Zn superoxide dismutase effectively protects bacteria from phagocytic killing,
      and that the role in infection of the redundant sodC genes may vary in distinct
      Salmonella enterica serovars. More unexpectedly, we have found that Cu,Zn
      superoxide dismutase also modulates bacterial survival within epithelial cells,
      where bacterial killing appears to be mediated by an NAD(P)H oxidase resembling
      the enzyme complex typical of phagocytes. Finally, a striking feature of Cu,Zn
      superoxide dismutases from bacterial pathogens is their apparent ability to
      exploit the structural versatility of the enzyme to modulate its function. In
      fact, several enzyme variants exhibit unique properties that may lead to the
      acquisition of novel specialized functions distinct from superoxide dismutation.

PMID- 14641057
TI  - Rotting by radicals--the role of cellobiose oxidoreductase?
AB  - Cellobiose oxidoreductase is a flavocytochrome secreted by wood-rotting fungi.
      The structure and functional role of the enzyme are reviewed, and a mechanism
      through which the enzyme produces superoxide, ferrous iron and hydrogen peroxide
      is proposed. The reactions of hydroxyl radicals formed by Fenton chemistry are
      discussed in the context of lignocellulose biodegradation.

PMID- 14641058
TI  - Kinetics of superoxide scavenging by glutathione: an evaluation of its role in
      the removal of mitochondrial superoxide.
AB  - Superoxide radicals are produced in trace amounts by the mitochondrial
      respiratory chain. Most are removed rapidly by superoxide dismutase in the
      matrix. Superoxide is also known to react with glutathione. Reported values of
      the rate constant for this reaction range from 10(2) to in excess of 10(5) M(
      1).s(-1). The magnitude of this rate constant has important physiological
      implications because, if it is at the upper end of the reported range, a
      significant proportion of mitochondrial superoxide will evade removal by
      superoxide dismutase, and will oxidize glutathione to the potentially harmful
      glutathionyl radical. Using EPR spectroscopy to monitor competition between
      glutathione and the spin trap 5,5-dimethyl-1-pyrroline N-oxide for reaction with
      superoxide, we have estimated that the rate constant for the reaction between
      superoxide and glutathione is only approximately 200 M(-1).s(-1). Hence
      superoxide dismutase will always out-compete glutathione for reaction with the
      superoxide radical, thereby preventing formation of the glutathionyl radical.

PMID- 14641059
TI  - The enzymatic defence against glycation in health, disease and therapeutics: a
      symposium to examine the concept.
AB  - Glycation of proteins, nucleotides and basic phospholipids by glucose, glyoxal,
      methylglyoxal, 3-deoxyglucosone and other saccharide derivatives is potentially
      damaging to the proteome and mutagenic. It is now recognized that there is an
      enzymatic defence against glycation--a group of enzymes that suppress the
      physiological levels of potent glycating agents and repair glycated proteins:
      glyoxalase I, aldehyde reductases and dehydrogenases, amadoriase and fructosamine
      3-phosphokinase. The enzymatic defence against glycation influences morbidity and
      the efficiency of drug therapy in certain diseases. Improved understanding of the
      balance between glycation and the enzymatic anti-glycation defence will advance
      disease diagnosis and therapy.

PMID- 14641060
TI  - Glyoxalase I--structure, function and a critical role in the enzymatic defence
      against glycation.
AB  - Glyoxalase I is part of the glyoxalase system present in the cytosol of cells.
      The glyoxalase system catalyses the conversion of reactive, acyclic alpha
      oxoaldehydes into the corresponding alpha-hydroxyacids. Glyoxalase I catalyses
      the isomerization of the hemithioacetal, formed spontaneously from alpha
      oxoaldehyde and GSH, to S -2-hydroxyacylglutathione derivatives [RCOCH(OH)-SG-
      >RCH(OH)CO-SG], and in so doing decreases the steady-state concentrations of
      physiological alpha-oxoaldehydes and associated glycation reactions.
      Physiological substrates of glyoxalase I are methylglyoxal, glyoxal and other
      acyclic alpha-oxoaldehydes. Human glyoxalase I is a dimeric Zn(2+) metalloenzyme
      of molecular mass 42 kDa. Glyoxalase I from Escherichia coli is a Ni(2+)
      metalloenzyme. The crystal structures of human and E. coli glyoxalase I have been
      determined to 1.7 and 1.5 A resolution. The Zn(2+) site comprises two
      structurally equivalent residues from each domain--Gln-33A, Glu-99A, His-126B,
      Glu-172B and two water molecules. The Ni(2+) binding site comprises His-5A, Glu
      56A, His-74B, Glu-122B and two water molecules. The catalytic reaction involves
      base-catalysed shielded-proton transfer from C-1 to C-2 of the hemithioacetal to
      form an ene-diol intermediate and rapid ketonization to the thioester product. R 
      and S-enantiomers of the hemithioacetal are bound in the active site, displacing
      the water molecules in the metal ion primary co-ordination shell. It has been
      proposed that Glu-172 is the catalytic base for the S-substrate enantiomer and
      Glu-99 the catalytic base for the R-substrate enantiomer; Glu-172 then
      reprotonates the ene-diol stereospecifically to form the R-2
      hydroxyacylglutathione product. By analogy with the human enzyme, Glu-56 and Glu
      122 may be the bases involved in the catalytic mechanism of E. coli glyoxalase I.
      The suppression of alpha-oxoaldehyde-mediated glycation by glyoxalase I is
      particularly important in diabetes and uraemia, where alpha-oxoaldehyde
      concentrations are increased. Decreased glyoxalase I activity in situ due to the
      aging process and oxidative stress results in increased glycation and tissue
      damage. Inhibition of glyoxalase I pharmacologically with specific inhibitors
      leads to the accumulation of alpha-oxoaldehydes to cytotoxic levels; cell
      permeable glyoxalase I inhibitors are antitumour and antimalarial agents.
      Glyoxalase I has a critical role in the prevention of glycation reactions
      mediated by methylglyoxal, glyoxal and other alpha-oxoaldehydes in vivo.

PMID- 14641061
TI  - Enzymatic deglycation with amadoriase enzymes from Aspergillus sp. as a potential
      strategy against the complications of diabetes and aging.
AB  - The Amadori compound is the major single modification of the extracellular matrix
      by the Maillard reaction in vivo. It is also a source of biologically active
      glycoxidation products and the formation of glucosepane, the major protein cross
      link found in biological tissues so far. For this reason, introduction of
      deglycating enzymes as anti-aging strategy would be desirable. This article
      provides an update on amadoriase enzymes from fungi which, one day, will
      hopefully help prevent the in vivo consequences of glycation.

PMID- 14641062
TI  - Fructosamine 3-kinase, an enzyme involved in protein deglycation.
AB  - The in vivo formation of fructosamines following non-enzymatic reaction of
      proteins with glucose (i.e. glycation) was first described almost 30 years ago.
      Until recently, the only known fate of fructosamines in mammalian cells was their
      spontaneous conversion into advanced glycation end products. The identification
      in human erythrocytes of a new enzyme, fructosamine 3-kinase, disclosed the
      existence of a so-far unsuspected intracellular metabolism of these compounds.
      Fructosamine 3-kinase phosphorylates with high affinity both low-molecular-mass
      and protein-bound fructosamines on the third carbon of their deoxyfructose
      moiety, leading to the formation of fructosamine 3-phosphates. The latter are
      unstable and spontaneously decompose into inorganic phosphate and 3
      deoxyglucosone, with concomitant regeneration of the unglycated amine. The
      presence of proteins related to fructosamine 3-kinase in many prokaryotic and
      eukaryotic genomes suggests that this 'deglycation' process is not restricted to
      mammals.

PMID- 14641063
TI  - Alpha-oxoaldehyde metabolism and diabetic complications.
AB  - The factors responsible for variable susceptibility to diabetic nephropathy are
      not clear. According to the non-enzymatic glycation hypothesis, diabetes-related
      tissue damage occurs due to a complex mixture of toxic products, including alpha
      oxoaldehydes, which are inherently toxic as well as serving as precursors for
      advanced glycation end-products. Protective mechanisms exist to control this
      unavoidable glycation, and these are determined by genetic or environmental
      factors that can regulate the concentrations of the reactive sugars or end
      products. In diabetes these protective mechanisms become more important, since
      glycation stress increases, and less efficient defence systems against this
      stress could lead to diabetic complications. Some of these enzymatic control
      mechanisms, including those that regulate alpha-oxoaldehydes, have been
      identified. We have observed significant increases in production of the alpha
      oxoaldehydes methylglyoxal and 3-deoxyglucosone in three human populations with
      biopsy-proven progression of nephropathy. The increase in methylglyoxal could be
      secondary to defects in downstream glycolytic enzymes (such as glyceraldehyde-3
      phosphate dehydrogenase) that regulate its production, or in detoxification
      mechanisms such as glyoxalase. Other mechanisms, however, appear to be
      responsible for the observed increase in 3-deoxyglucosone levels. We present
      results of our studies on the mechanisms responsible for variable production of
      alpha-oxoaldehydes by measuring the activity and characteristics of these enzymes
      in cells from complication-prone and -resistant diabetic patients. New
      therapeutic interventions designed to control these endogenous mechanisms could
      potentially enhance protection against excessive glycation and prevent or reverse
      complications of long-term diabetes.

PMID- 14641064
TI  - Role of genetic variability in systems of receptor-mediated and enzymatic defence
      against glycation in the long-term consequences of diabetes mellitus.
AB  - Diabetes mellitus is the most common metabolic disease, and has late
      complications that are due to chronic hyperglycaemia. Altered carbohydrate and
      lipid metabolism together with impaired detoxification of carbonyl substrates and
      impaired trapping of oxygen radicals are responsible for cell damage in diabetes.
      Variable functional capacity of detoxifying systems could contribute to differing
      susceptibility to the development of complications. Identification of genetic
      variants responsible for modulating relevant intermediate phenotypes in diabetics
      could help to define individual risk profiles and to modify therapeutic strategy
      accordingly.

PMID- 14641065
TI  - Aldose reductase and the importance of experimental design.
AB  - Kinetic studies on the AR (aldose reductase) protein have shown that it does not
      behave as a classical enzyme in relation to ring aldose sugars. As with non
      enzymatic glycation reactions, there is probably a free-radical element involved
      derived from monosaccharide autoxidation. In the case of AR, there is free
      radical oxidation of NADPH by autoxidizing monosaccharides, which is enhanced in
      the presence of the NADPH-binding protein. Thus any assay for AR based on the
      oxidation of NADPH in the presence of autoxidizing monosaccharides is invalid,
      and tissue AR measurements based on this method are also invalid, and should be
      reassessed. AR exhibits broad specificity for both hydrophilic and hydrophobic
      aldehydes that suggests that the protein may be involved in detoxification. The
      last thing we would want to do is to inhibit it. ARIs (AR inhibitors) have a
      number of actions in the cell which are not specific, and which do not involve
      them binding to AR. These include peroxy-radical scavenging and effects of metal
      ion chelation. The AR/ARI story emphasizes the importance of correct experimental
      design in all biocatalytic experiments. Developing the use of Bayesian utility
      functions, we have used a systematic method to identify the optimum experimental
      designs for a number of kinetic model data sets. This has led to the
      identification of trends between kinetic model types, sets of design rules and
      the key conclusion that such designs should be based on some prior knowledge of K
      (m) and/or the kinetic model. We suggest an optimal and iterative method for
      selecting features of the design such as the substrate range, number of
      measurements and choice of intermediate points. The final design collects data
      suitable for accurate modelling and analysis and minimizes the error in the
      parameters estimated, and is suitable for simple or complex steady-state models.

PMID- 14641066
TI  - Protecting the genome: defence against nucleotide glycation and emerging role of
      glyoxalase I overexpression in multidrug resistance in cancer chemotherapy.
AB  - Glycation of nucleotides in DNA forms AGEs (advanced glycation end-products).
      Nucleotide AGEs are: the imidazopurinone derivative dG-G [3-(2'-deoxyribosyl)-6,7
      dihydro-6,7-dihydroxyimidazo[2,3-b]purin-9(8)one], CMdG ( N (2)
      carboxymethyldeoxyguanosine) and gdC (5-glycolyldeoxycytidine) derived from
      glyoxal, dG-MG [6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one],
      dG-MG(2) [ N (2),7-bis-(1-hydroxy-2-oxopropyl)deoxyguanosine] and CEdG [ N (2)-(1
      carboxyethyl)deoxyguanosine] derived from methylglyoxal, and dG-3DG [ N (2)-(1
      oxo-2,4,5,6-tetrahydroxyhexyl)deoxyguanosine] derived from 3-deoxyglucosone and
      others. Glyoxal and methylglyoxal induce multi-base deletions, and base-pair
      substitutions - mostly occurring at G:C sites with G:C-->C:G and G:C-->T:A
      transversions. Suppression of nucleotide glycation by glyoxalase I and aldehyde
      reductases and dehydrogenases, and base excision repair, protects and recovers
      DNA from damaging glycation. The effects of DNA glycation may be most marked in
      diabetes and uraemia. Mutations arising from DNA glycation may explain the link
      of non-dietary carbohydrate intake to incidence of colorectal cancer.
      Overexpression of glyoxalase I was found in drug-resistant tumour cells and may
      be an example of an undesirable effect of the enzymatic protection against DNA
      glycation. Experimental overexpression of glyoxalase I conferred resistance to
      drug-induced apoptosis. Glyoxalase I-mediated drug resistance was found in human
      leukaemia and lung carcinoma cells. Methylglyoxal-mediated glycation of DNA may
      contribute to the cytotoxicity of some antitumour agents as a consequence of
      depletion of NAD(+) by poly(ADP-ribose) polymerase, marked increases in
      triosephosphate concentration and increased formation of methylglyoxal. S - p 
      Bromobenzylglutathione cyclopentyl diester is a cell-permeable glyoxalase I
      inhibitor. It countered drug resistance and was a potent antitumour agent against
      lung and prostate carcinoma. Glyoxalase I overexpression was also found in
      invasive ovarian cancer and breast cancer.

PMID- 14641067
TI  - Glyoxalase I inhibitors in cancer chemotherapy.
AB  - Several recent developments suggest that the GSH-dependent glyoxalase enzyme
      system deserves renewed interest as a potential target for antitumour drug
      development. This summary focuses on the design and development of new classes of
      tumoricidal agents that specifically target this elementary detoxification
      pathway in order to induce elevated concentrations of cytotoxic methylglyoxal in
      tumour cells. Special emphasis is placed on structure- and mechanism-based
      inhibitors of GlxI (glyoxalase I), the first enzyme in the pathway. A new class
      of bivalent transition-state analogues is described that simultaneously bind the
      active site on each subunit of the homodimeric human GlxI, resulting in K (i)
      values as low as 1 nM. Also described is a new family of bromoacyl esters of GSH
      that function as active-site-directed irreversible inhibitors of GlxI. Newer
      prodrugs for delivering the GSH-based inhibitors into tumour cells include
      reactive sulphoxide esters that undergo acyl exchange with endogenous GSH to give
      the inhibitors, and polymethacrylamide esters of the inhibitors that are
      potentially tumour-selective on the basis of the "enhanced permeability and
      retention effect". Finally, a preliminary evaluation of the efficacy of selected
      GlxI inhibitors in tumour-bearing mice is given.

PMID- 14641068
TI  - Glycation in food and metabolic transit of dietary AGEs (advanced glycation end
      products): studies on the urinary excretion of pyrraline.
AB  - Pyrraline [epsilon-(2'-formyl-5'-hydroxymethyl-pyrrolyl)-L-norleucin] belongs to
      the group of AGEs (advanced glycation end-products) formed in the final stage of
      the Maillard reaction in foods and in vivo. As it is generally accepted that AGEs
      are pathophysiologically relevant in aging and in diseases such as diabetes and
      uraemia, physiological consequences resulting from the ingestion of dietary AGEs
      are discussed, but balance studies for well defined AGEs are still lacking. The
      aim of our study was to investigate the influence of nutrition on the urinary
      excretion of pyrraline. After the first day without dietary restrictions, seven
      healthy volunteers were asked, starting on the morning of day 2, to ingest a diet
      virtually free of Maillard compounds (i.e. no cooked or roasted foods, no bakery
      products, no coffee, etc.). Dietary control was stopped on the morning of day 5.
      We collected 24 h urine samples for these 5 days, which were analysed for free
      pyrraline by reverse-phase HPLC with UV detection at 297 nm. We found that
      urinary excretion of free pyrraline was directly affected by the composition of
      the diet, decreasing from 4.8+/-1.1 mg/day on day 1 to levels of 1.6, 0.4 and 0.3
      mg/day on days 2, 3 and 4 respectively, followed by a significant increase to
      3.2+/-1.4 mg/day on the 5th day. The results of this work prove, for the first
      time, that urinary excretion of pyrraline is strongly dependent on its dietary
      intake. Thus the influence of nutrition should be taken into consideration in
      studies directed to the physiological role of glycation compounds.

PMID- 14641069
TI  - Renal clearance of glycation adducts: anti-glycation defence in uraemia and
      dialysis.
AB  - Increased plasma concentrations of free AGEs (advanced glycation end products) in
      uraemia are due to impaired renal clearance exacerbated by dietary load and
      breakdown of the elevated protein-bound AGEs. Increased protein-bound AGEs most
      probably reflect increased synthesis due to the increased oxidative and carbonyl
      stress of uraemia, which is exacerbated by the dialysis procedure. Use of
      biocompatible peritoneal dialysis fluids and haemodialysis membranes will be
      beneficial, but strategies to further reduce AGE formation are required. These
      should focus on the hydroimidazalone AGEs, which are quantitatively the most
      important, and not only on the conventionally monitored AGEs N (epsilon)
      carboxymethyl-lysine and pentosidine.

PMID- 14641070
TI  - Toxicity of glyoxals--role of oxidative stress, metabolic detoxification and
      thiamine deficiency.
AB  - Glyoxals are reactive alpha-oxoaldehydes that are formed endogenously from
      sugars, the levels of which are increased in various pathological conditions
      associated with hyperglycaemia and thiamine deficiency. However, the molecular
      cytotoxic mechanisms of glyoxal are not known. Results presented here and in the
      other studies cited provide a glimpse into the cytotoxicity mechanisms involved
      and their pathological implications. We found that glyoxal (10 microM) markedly
      increased the susceptibility of hepatocyte glutathione (GSH) to oxidation by
      hydrogen peroxide (H(2)O(2)) and markedly increased cytotoxicity by compromising
      the cellular antioxidant enzyme system. At higher concentrations, glyoxal was
      cytotoxic towards hepatocytes, which can be attributed to GSH depletion,
      oxidative stress and mitochondrial toxicity. Aminoguanidine or penicillamine
      protected the hepatocytes. Glyoxal cytotoxicity was prevented by increasing
      glyoxal metabolism with thiamine or NAD(P)H generators, and was increased in GSH-
      or thiamine-deficient hepatocytes. It was also found that feeding rats reduced
      thiamine levels in a diet high in simple sugars increased the number of aberrant
      crypt foci/colon in the absence of clinical evidence of beriberi. This was
      associated with decreased plasma thiamine and low erythrocyte transketolase
      activity. Western diets, which are frequently poor in thiamine and high in
      sugars, could result in increased levels of endogenous glyoxals, which in turn
      may lead to a predisposition to AGE (advanced glycation end-product)-related
      pathologies and neoplastic conditions.

PMID- 14641071
TI  - Removal of advanced glycation end products in clinical renal failure by
      peritoneal dialysis and haemodialysis.
AB  - AGEs (advanced glycation end products) accumulate markedly in the plasma of human
      subjects with renal failure. We investigated the efficiency of removal of AGEs
      from the circulation by PD (peritoneal dialysis) and HD (haemodialysis) therapy.
      Free AGEs were measured by LC-MS/MS in blood plasma before dialysis, in dialysis
      fluid effusate after a 2-12 h dwell time in the peritoneal cavity of PD subjects,
      and in the HD dialysate before and after HD therapy. In clinical uraemia, the
      concentrations of free AGEs in blood plasma were increased up to 50-fold. For
      example, levels of MG-H1 (methylglyoxal-derived hydroimidazolone) were: normal
      controls, 110+/-46 nM; PD subjects, 1876+/-676 ( P <0.01); HD subjects, 5496+/
      1138 nM ( P <0.001). In PD subjects, the AGE concentration in the effusate
      increased with increasing dwell time, reaching a maximum at a concentration
      higher than that in plasma for some AGEs at 4-12 h. This may reflect AGE
      formation in the peritoneal cavity. In HD, AGE concentrations in HD fluid were
      decreased markedly from the start to the end of a dialysis session, except that
      levels of the methylglyoxal-derived AGEs N (epsilon)-(1-carboxyethyl)lysine and
      MG-H1, and of pentosidine, remained 5-fold higher than control levels. Inadequate
      clearance of free AGEs may be linked to the increased risk of cardiovascular
      disease in patients with renal failure.

PMID- 14641072
TI  - Anti-AGEing defences against Alzheimer's disease.
AB  - Accumulation of insoluble protein deposits and their cross-linking by AGEs
      (advanced glycation end products) in the brain is a feature of aging and
      neurodegeneration, especially in AD (Alzheimer's disease). In AD, two types of
      fibrillar protein aggregates are present: extracellular deposits (plaques)
      consisting mainly of Abeta (beta-amyloid peptide), and intracellular deposits
      (tangles) composed predominantly of microtubule-associated protein tau. Both
      plaques and tangles are modified by AGEs, which occurs particularly at lysine and
      arginine residues. Interaction of a synthetic amyloid plaque (fibrillar Abeta)
      with microglia leads to a strong pro-inflammatory response, indicating that
      priming of immune cells with beta-amyloid potentiates their response to secondary
      stimuli such as AGE and cytokines such as interferon-gamma. Formation of
      hyperphosphorylated and cross-linked microtubule-associated protein tau
      aggregates, especially tau dimers as the first step in tangle formation, can be
      induced in vitro by the combination of okadaic acid, a PP2A phosphatase
      inhibitor, and methylglyoxal. These results suggest that excess production of
      reactive carbonyl compound ("carbonyl stress") and subsequent AGE formation can
      contribute to cross-linking of protein fibrils and to pathological pro
      inflammatory signalling, which all contribute to pathological changes and
      dementia progression in AD. However, the human brain has developed the glyoxalase
      system, a most effective defence system to scavenge small dicarbonyl compounds
      such as glyoxal and methylglyoxal. Very importantly, this system needs GSH as a
      rate-limiting cofactor. Since GSH is limited under conditions of oxidative stress
      and inflammation, supplementation with antioxidants such as lipoic acid, vitamin
      E or flavonoids could indirectly strengthen the anti-glycation defence system in
      AD. In addition, synthetic carbonyl scavengers and anti-inflammatory drugs could
      also be valuable drugs for the "anti-glycation" treatment of AD.

PMID- 14641073
TI  - Role of methylglyoxal adducts in the development of vascular complications in
      diabetes mellitus.
AB  - Various theories have been proposed to explain the hyperglycaemia-induced
      pathogenesis of vascular complications of diabetes, including detrimental effects
      of AGEs (advanced glycation end products) on vascular tissues. Increased
      formation of the very reactive dicarbonyl compound MGO (methylglyoxal), one of
      the side-products of glycolysis, and MGO-derived AGEs seem to be implicated in
      the development of diabetic vascular complications. Although the exact role of
      MGO and MGO adducts in the development of vascular complications is unknown,
      receptor-mediated activation of vascular cells by the MGO-arginine adduct
      hydroimidazolone, as well as intracellular modifications of protein by MGO, seem
      to be involved. The aim of this mini-review is to assess to what extent MGO is
      related to vascular complications in diabetes.

PMID- 14641074
TI  - Protein modification by advanced Maillard adducts can be modulated by dietary
      polyunsaturated fatty acids.
AB  - Advanced Maillard adducts, such as N epsilon-(carboxymethyl)lysine and N epsilon
      (carboxyethyl)lysine, can be formed efficiently in vitro from both peroxidation
      of polyunsaturated fatty acids and glycolysis intermediates. In an attempt to
      differentiate the in vivo influence of the two pathways in these modifications,
      Wistar rats were chronically fed with specially designed diets rich in saturated
      or unsaturated fats. The degree of fatty acid unsaturation of all analysed organs
      (liver, kidney, brain) was altered by these dietary stresses. Protein
      glycoxidative and lipoxidative modifications were measured by GC/MS. In
      accordance with fatty acid profiles, concentrations of N epsilon
      (malondialdehyde)lysine in these tissues were significantly increased in animals
      fed the unsaturated fat diet. In contrast, N epsilon-(carboxymethyl)lysine and N
      epsilon-(carboxyethyl)lysine concentrations were strongly dependent on the tissue
      analysed; although the unsaturated fat diet increased their levels significantly
      in brain, levels were unchanged in kidney and decreased in liver. These later
      results could be interpreted on the basis that polyunsaturated fatty acids
      decrease the expression of several glycolytic enzymes in liver. Globally, these
      data suggest that tissue-specific metabolic characteristics play a key role in
      the degree of cellular protein modification by Maillard reactions, e.g. by
      modulation of the concentration of glycolysis intermediates or via specific
      defensive systems in these organs.

PMID- 14641075
TI  - Bacterial production of methylglyoxal: a survival strategy or death by
      misadventure?
AB  - The production of MG (methylglyoxal) in bacterial cells must be maintained in
      balance with the capacity for detoxification and protection against this
      electrophile. Excessive production of MG leads to cell death. Survival of
      exposure to MG is best understood in the Gram-negative bacteria. The major
      mechanism of protection is the spontaneous reaction of MG with GSH to form
      hemithiolacetal, followed by detoxification by the glyoxalase system leading to
      the production of D-lactate. The KefB and KefC glutathione-gated K(+) efflux
      systems are integrated with the activity of the glyoxalase system to regulate the
      cytoplasmic pH in response to exposure to electrophiles. Bacteria only produce MG
      when an imbalance occurs in metabolism. Operation of the MG bypass enables cells
      to adapt, such that balance is restored to metabolism. Excessive production of MG
      is an adaptive ploy, which, if it fails, has fatal consequences. On this basis
      one might define MG-induced loss of life as "death by misadventure" rather than
      suicide!

PMID- 14641076
TI  - Anti-glycation defences in yeast.
AB  - Saccharomyces cerevisiae is an outstanding cellular model for metabolic studies
      in glycation. Due to its high glycolytic activity, it produces methylglyoxal, a
      highly reactive intracellular glycation agent, at a rate of approx. 0.1% of the
      glycolytic flux. We investigated methylglyoxal metabolism in Saccharomyces
      cerevisiae cells, using haploid null mutants. Growth studies showed that the most
      sensitive strains to 2-oxoaldehydes were the null mutants for GSH1 and GLO1,
      coding for glutathione synthase I and glyoxalase I respectively. The GRE3 null
      mutant, lacking aldose reductase activity, is as sensitive as the control strain.
      Kinetic modelling and computer simulation of this type of experiment were also
      performed, and we concluded that the most important parameters for controlling
      the intracellular concentration of methylglyoxal are the activity of glyoxalase I
      and the GSH concentration. Moreover, our model predicts an intracellular steady
      state concentration of methylglyoxal of approx. 2 microM. Our results show that
      the glyoxalase pathway is the main detoxification pathway for 2-oxoaldehydes in
      yeast, and is likely to be the key enzymatic anti-glycation agent in these cells.

PMID- 14641077
TI  - Role of lipids in chemical modification of proteins and development of
      complications in diabetes.
AB  - Hyperglycaemia is the major risk factor for the development of complications in
      both Type I and Type II diabetes; however, there is growing evidence from several
      clinical trials that dyslipidaemia, including hypertriglyceridaemia, is a
      significant and independent risk factor for diabetic complications. In this
      paper, we propose that chemical modification of proteins by lipids may be a
      underlying pathogenic mechanism linking dyslipidaemia to diabetic complications.
      Thus the major AGEs (advanced glycation end-products) in tissues, such as
      carboxymethyl-lysine, carboxyethyl-lysine and hydroimidazolones, may, in fact, be
      ALEs (advanced lipoxidation end-products), derived from lipids. Increased lipid
      peroxidation and accelerated ALE formation, possibly catalysed by hyperglycaemia
      and oxidative stress, may be the mechanistic link between dyslipidaemia and
      diabetic complications. If correct, this proposal would suggest that inhibition
      or reversal of glycation, which is a central theme of this symposium, may not be
      sufficient for protection against diabetic complications.

PMID- 14641078
TI  - Quantitative screening of protein biomarkers of early glycation, advanced
      glycation, oxidation and nitrosation in cellular and extracellular proteins by
      tandem mass spectrometry multiple reaction monitoring.
AB  - Glycation of proteins forms fructosamines and AGEs (advanced glycation end
      products). Oxidative and nitrosative stress leads to the formation of oxidative
      and nitrosative modifications. The modified amino acid residues formed in these
      processes are biomarkers of protein damage: some are risk markers and some may be
      risk factors for disease development. We developed a method for the concurrent
      quantitative measurement of 16 biomarkers indicative of protein glycation,
      oxidation and nitrosation damage using LC-MS/MS (LC with tandem MS detection).
      Underivatized analytes were detected free in physiological fluids and in
      enzymatic hydrolysates of cellular and extracellular proteins. Hydroimidazolones
      were the most important glycation biomarkers, and methionine sulphoxide was the
      most important oxidative biomarker quantitatively; 3-nitrotyrosine was the
      biomarker of nitrosation. Quantitative screening showed high levels of AGEs in
      cellular protein and moderate levels in protein of blood plasma. Levels of 3
      nitrotyrosine were typically 100-fold lower than this. The major glycation
      adducts in blood plasma had high renal clearances in normal healthy human
      subjects, whereas methionine sulphoxide and 3-nitrotyrosine had low renal
      clearances due to further metabolism. Physiological AGEs in blood plasma were
      eliminated from the circulation in the kidney and not in the liver. LC-MS/MS
      peptide mapping was also used to locate the protein biomarkers. These studies
      reveal that advanced glycation is a significant modification of cellular and
      extracellular protein. The enzymatic defences against glycation, antioxidants and
      proteasomal protein degradation inside cells are probable factors regulating
      biomarker levels of cellular protein.

PMID- 14641080
TI  - Mass spectrometric analysis of glucose-modified ribonuclease.
AB  - RNase A (1 mM) was incubated with glucose (0.4 M) at 37 degrees C for up to 14
      days in phosphate buffer (0.2 M, pH 7.4), digested with trypsin and analysed by
      LC-MS. The major sites of fructoselysine formation were Lys(1), Lys(7), Lys(37)
      and Lys(41). Three of these sites (Lys(7), Lys(37) and Lys(41)) were also the
      major sites of N epsilon-(carboxymethyl)lysine formation.

PMID- 14641079
TI  - Accumulation of fructosyl-lysine and advanced glycation end products in the
      kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats.
AB  - The accumulation of AGEs (advanced glycation end products) in diabetes mellitus
      has been implicated in the biochemical dysfunction associated with the chronic
      development of microvascular complications of diabetes--nephropathy, retinopathy
      and peripheral neuropathy. We investigated the concentrations of fructosyl-lysine
      and AGE residues in protein extracts of renal glomeruli, retina, peripheral nerve
      and plasma protein of streptozotocin-induced diabetic rats and normal healthy
      controls. Glycation adducts were determined by LC with tandem MS detection. In
      diabetic rats, the fructosyl-lysine concentration was increased markedly in
      glomeruli, retina, sciatic nerve and plasma protein. The concentrations of N
      (epsilon)-carboxymethyl-lysine and N (epsilon)-carboxyethyl-lysine were increased
      in glomeruli, sciatic nerve and plasma protein, and N(epsilon)-carboxymethyl
      lysine also in the retina. Hydroimidazolone AGEs derived from glyoxal,
      methylglyoxal and 3-deoxylglucosone were major AGEs quantitatively. They were
      increased in the retina, nerve, glomeruli and plasma protein. AGE accumulation in
      renal glomeruli, retina, peripheral nerve and plasma proteins is consistent with
      a role for AGEs in the development of nephropathy, retinopathy and peripheral
      neuropathy in diabetes. High-dose therapy with thiamine and Benfotiamine
      suppressed the accumulation of AGEs, and is a novel approach to preventing the
      development of diabetic complications.

PMID- 14641081
TI  - Enzymatic deglycation--a new paradigm or an epiphenomenon?
AB  - Following the discovery of FN3K (fructosamine 3-kinase), and more recently of
      FN3KRP (FN3K-related protein), research in our laboratory has been focused on
      testing the enzymatic deglycation hypothesis and investigating the roles of FN3K
      and FN3KRP. Thus far, using human erythrocytes as a model system, we have
      obtained the following evidence of enzymatic deglycation: (a) production of GHb
      (glycated haemoglobin) by D-glucose in intact erythrocytes is 5-fold lower than
      in haemolysates; (b) glycation of GHb by D-glucose in intact erythrocytes is 5
      fold lower than that by L-glucose; (c) inhibition of ATP production in
      erythrocytes leads to an acceleration in the rate of GHb production by D-glucose;
      and (d) inhibition of FN3K in erythrocytes by a competitive inhibitor increases
      the accumulation of GHb. In spite of these data supporting the enzymatic
      deglycation hypothesis, some outstanding issues remain. These include, among
      others, the fact that while the apparent deglycation mechanism does not operate
      on L-glucose, semi-purified FN3K appears to be able to use both D- and L
      fructosamines as substrates. Moreover, analysis of the fructoselysine 3-phosphate
      content of haemoglobin from diabetic subjects suggests that, in addition to FN3K,
      another deglycating mechanism may be operative in human erythrocytes. Elucidation
      of these issues is a challenge in the evolving field of deglycation research.
      Most important, however, is the question of whether enzymatic deglycation is
      truly an important defence mechanism or merely an epiphenomenon.

PMID- 14641082
TI  - Modulation of in vivo 3-deoxyglucosone levels.
AB  - Fructoselysine 3-phosphate is synthesized in vivo by the recently discovered
      fructoseamine-3-kinase (F3K) from fructoselysine and ATP and decomposes to
      lysine, P(i) and 3-deoxyglucosone (3DG). This pathway appears to dominate 3DG
      production in vivo, making it possible to modulate 3DG levels by stimulating or
      inhibiting the reaction. Present inhibitors are non-reacting substrate analogues
      with relatively high K (i) values and can inhibit F3K sufficiently in vivo to
      reduce 3DG in diabetic rat plasma by approx. 50%. Stimulation of the F3K pathway
      by feeding glycated casein causes an increase of 10-20-fold in plasma levels of
      3DG and 3-fold in kidney tubules. Consequences of this increase were studied in
      two systems: the Eker rat, a model of susceptible kidney tubules; and birth rates
      in two rat strains. In both cases substantial pathological effects were observed.
      In the Eker rats, an approx. 3-fold increase in kidney lesions was observed ( P
      <0.00001). In both Fischer 344 and Sprague-Dawley rats, birth rates were reduced
      by 56% ( P <0.0001) and 12% ( P <0.015) respectively. These results suggest that
      inhibition of F3K is a promising new therapeutic target for diabetic
      complications, as well as other 3DG-dependent pathologies.

PMID- 14641083
TI  - Application of monoclonal antibody libraries for the measurement of glycation
      adducts.
AB  - Immunological approaches have been used to demonstrate the presence of advanced
      glycation end-products (AGEs) in several human and experimental animal tissues.
      We previously prepared polyclonal and monoclonal anti-AGE antibodies by
      immunizing AGE-modified proteins such as BSA and RNase. Although these antibodies
      contributed to demonstrate the presence of AGE-modified protein in vivo, the
      epitope structure of these antibodies had not been identified. We subsequently
      prepared several antibodies against AGE structures such as pentosidine,
      pyrraline, 3-deoxyglucosone imidazolone and N epsilon-(carboxyethyl)lysine by
      immunizing single AGE structures. These structure-specific antibodies have
      greatly helped broaden our understanding of AGE structures in aging and age
      enhanced disease process. Monoclonal anti-AGE antibody is also used for the
      identification of major AGE structures in some pathological tissues, such as
      human atherosclerosis lesions. Based on the strategy, we successfully identified
      a novel AGE structure named glycolaldehyde-pyridine, which is the major antigenic
      AGE derived from glycolaldehyde. Therefore a monoclonal antibody library for AGE
      structures has served an important role in the elucidation of the biological
      significance of AGE.

PMID- 14641084
TI  - Reactive oxygen species in oncogenic transformation.
AB  - Ever since ROS (reactive oxygen species) were shown to meet the criteria of true
      signalling molecules, such as regulated production and a specific biological
      function, many efforts have been made to understand the precise role of ROS. The
      function of ROS in pathological mechanisms is taking a more and more central role
      in various fields of biomedical research, including neurobiology, cardiology and
      cancer. An elevated oxidative status has been found in many types of cancer
      cells, and the introduction of chemical and enzymological antioxidants can
      inhibit tumour cell proliferation, pointing to a critical role of ROS in
      mediating loss of growth control. The present review describes ROS-regulated
      mechanisms that are associated with cancer and tumour invasiveness. The cellular
      processes that are linked to these ROS functions are mitogenic signalling and
      cell motility, while ROS have also been implicated in apoptosis and cellular
      senescence, two mechanisms regarded as being anti-tumorigenic. This "two-faced"
      character of free radicals will be discussed and placed in the context of the
      physiological conditions of the tumour cell, the different molecular backgrounds,
      and the specific ROS. More detailed understanding of the signalling pathways
      regulated by ROS in tumour cells will open up new prospects for chemo- or gene
      therapeutic interventions.

PMID- 14641085
TI  - Sprouty: a controversial role in receptor tyrosine kinase signalling pathways.
AB  - Sprouty was first identified in Drosophila as a novel antagonist of the
      fibroblast growth factor signalling pathway. Sprouty proteins comprise a big
      family, members of which are characterized by a cysteine-rich domain which
      confers inhibitory activity, whereas differences in the N-terminal region may be
      responsible for functional divergence. The role of Sprouty in RTK (receptor
      tyrosine kinase) signalling pathways is still controversial. Sprouty may
      negatively or positively regulate RTK signalling via differential interaction
      with different signalling molecules, and hence exert different mechanism of
      action.

PMID- 14641086
TI  - Vascular endothelial dysfunction in aging: loss of Akt-dependent endothelial
      nitric oxide synthase phosphorylation and partial restoration by (R)-alpha-lipoic
      acid.
AB  - Aging is the single largest risk factor for cardiovascular diseases, which in
      turn are the leading cause of death of individuals over the age of 65 years. In
      part, this risk is due to a profound loss of vasomotor function of the major
      conduit arteries, primarily because of lower levels of endothelial-derived nitric
      oxide. The mechanisms involved in vascular dysfunction are not entirely
      understood, but age-related alterations in eNOS (endothelial nitric oxide
      synthase) activity appear to be a likely source of the aging lesion. However, age
      related changes in cell signalling that ultimately affect eNOS phosphorylation
      and its activity have not been explored. Results in our laboratory indicate that
      levels of eNOS phosphorylation in aortas from aged F344xBN rats (28-30 months
      old) are almost 50% lower than in aortas from young animals (3 months old). Lower
      eNOS phosphorylation is directly attributable to loss of constitutive Akt/protein
      kinase B activity. The decline in eNOS phosphorylation can be partially restored
      by treating old rats with (R)-alpha-lipoic acid. These results thus suggest that
      age-related changes in eNOS phosphorylation may be a significant factor in the
      overall loss of vasomotor function in the elderly.

PMID- 14641087
TI  - Rapid S-nitrosothiol metabolism by platelets and megakaryocytes.
AB  - RSNOs (S-nitrosothiols) regulate platelet and megakaryocyte function, and may act
      in vivo as a nitric oxide reservoir. There is a discrepancy between the
      spontaneous rate of NO release from different RSNO compounds and their
      pharmacological effects, implying that target cells may mediate biological
      activity either by metabolism of RSNOs or by displaying cell surface receptors.
      In the present study, we sought evidence for rapid cell-mediated metabolism of
      RSNOs. Exposure of platelets to GSNO (S-nitrosoglutathione) for as little as 5 s
      inhibited thrombin-induced platelet aggregation by >95%; however, AlbSNO (S
      nitrosoalbumin) was much less effective over these short time periods. Incubation
      of 1 microM GSNO or AlbSNO with platelets and megakaryocytes resulted in a 25-34%
      loss of RSNO recoverable from the supernatant (P <0.02) within 30 s. This rapid
      cell-mediated RSNO decay did not progress further over 5 min, and could not be
      accounted for by release of free NO. The gamma-glutamyl transpeptidase inhibitor
      acivicin (100 microM) partially decreased GSNO decay, whereas the membrane
      impermeable thiol-blocking agent 5,5'-dithiobis-(2-nitrobenzoic acid) (100
      microM) completely blocked cell-mediated GSNO decay and partially blocked AlbSNO
      decay. Our results highlight differences between high- and low-molecular-mass
      RSNOs with regard to their rapid metabolism/uptake and subsequent cellular
      responses, and indicate a critical role for extracellular thiols in RSNO
      metabolism by platelets and megakaryocytes.

PMID- 14641088
TI  - Co-localization of cell surface receptors at high spatial resolution by single
      particle fluorescence imaging.
AB  - Dual-wavelength single-particle fluorescence imaging has been used to quantify
      the co-localization of receptors and/or ligands on cells by widefield microscopy.
      Methods for correction of chromatic aberration and identification of
      submicroscopic artefacts are presented, with data for the lipopolysaccharide/CD14
      and MHC class II/CD74 systems.

PMID- 14641089
TI  - Unravelling Nature's networks.
AB  - Dramatic progress has been made recently in determining the genetic and molecular
      composition of cells. This has prompted the development of new approaches to the
      challenge of understanding how basic cellular mechanisms are coordinated to
      produce the dazzling complexity of living systems. To face this challenge fully,
      it is critical not only to know what genes and proteins are expressed in cells,
      but also to understand the spatiotemporal dynamics of their networks of
      interactions. The sheer scale and complexity of cellular interaction networks
      necessitates a multi-disciplinary effort in which sophisticated experimental
      techniques are employed in combination with computational analysis and
      mathematical modelling. Such approaches are beginning to provide insight into
      basic structures and mechanisms, and promise to become critical to the post
      genomic mission of understanding the cell as a complex dynamical system.

PMID- 14641090
TI  - Signalling networks, inflammation and innate immunity.
AB  - We have been analysing the signalling systems that couple to receptors of the TIR
      (Toll/interleukin-1 receptor) family, which signal through a common cytoplasm
      region; the TIR domain. These systems are of both practical and fundamental
      biological significance, being central to the pathogenesis of chronic
      inflammatory diseases such as atherosclerosis, to host defence throughout the
      biological world, and are ancient in the context of life on earth, having
      originated more than 1 billion years ago: prior to the divergence of plants and
      animals. TIR domain receptors couple to at least two sets of well-characterized
      pathways: those leading to the activation of inhibitory kappaB kinase
      complexes/nuclear factor kappaB, and those leading to the activation of mitogen
      activated protein kinase/AP-1/ATF-2 etc. We have been investigating these systems
      using a combination of expression screening methods to identify new components,
      and real-time green fluorescent protein-based techniques to observe execution of
      signalling programmes in real time. Our data reveal that there is a very large
      level of cell-to-cell variation in signal programme execution even in clonal
      populations and that at least one mechanism for dealing with this heterogeneity
      is the assembly of signal transduction components into large multiprotein
      complexes.

PMID- 14641091
TI  - Systems biology markup language: Level 2 and beyond.
AB  - The SBML (systems biology markup language) is a standard exchange format for
      computational models of biochemical networks. We continue developing SBML
      collaboratively with the modelling community to meet their evolving needs. The
      recently introduced SBML Level 2 includes several enhancements to the original
      Level 1, and features under development for SBML Level 3 include model
      composition, multistate chemical species and diagrams.

PMID- 14641092
TI  - Extracting meaning from microarray data.
AB  - Gene expression is complex: many mRNAs change in abundance in response to a new
      condition. But while some of these expression changes may be direct, many may be
      downstream, indirect effects. One of the major problems of microarray data
      analysis is distinguishing between these changes. Some of the most common methods
      of analysis are discussed, in the context of their ability to distinguish between
      direct and indirect expression changes. The application of modular control
      analysis to microarray data in order to partition and quantify the importance of
      mRNA clusters in mediating responses is described.

PMID- 14641093
TI  - Interpreting correlations in metabolomic networks.
AB  - Correlations, as observed between the concentrations of metabolites in a
      biological sample, may be used to gain additional information about the
      physiological state of a given tissue. In this mini-review, we discuss the
      integration of these observed correlations into metabolomic networks and their
      relationships with the underlying biochemical pathways.

PMID- 14641094
TI  - Deriving statistical models for predicting peptide tandem MS product ion
      intensities.
AB  - Improved search algorithms and scoring functions are required before the
      identification of peptide tandem MS data can be considered to be fully reliable
      and automatable. The development of models that can accurately predict product
      ion spectra from a peptide sequence would certainly help achieve this goal, but
      this firstly requires a better understanding of the process of fragmentation of
      peptides in the gas-phase. We summarize recent developments in this area and show
      that the prediction of product ion spectra is feasible and should improve the
      identification of peptide tandem MS data, especially for peptides that currently
      give low or insignificant scores with current search algorithms.

PMID- 14641095
TI  - Integrating functional genomics data.
AB  - Functional annotation of fully sequenced genomes is still a major issue. High
      throughput data sets could be used to provide more and better functional
      annotations. However differences in data quality need to be taken into account.
      For this purpose these high-throughput data sets need to be integrated so that
      the data quality can be assessed, hypotheses can be prioritized and existing
      annotations can be improved and extended.

PMID- 14641096
TI  - Identification of surrogate markers for determining drug activity using
      proteomics.
AB  - In a high proportion of human carcinomas overexpression of the EGFR (epidermal
      growth factor receptor), a receptor tyrosine kinase, represents a potential
      target for cancer treatment. EGFR is induced to dimerize through ligand binding
      which activates the tyrosine kinase activity of the receptor. This catalyses the
      transfer of ATP's gamma-phosphate to hydroxyl groups of tyrosine residues on the
      receptor, creating binding sites that recruit downstream signalling proteins. New
      drugs, SMTKIs (small-molecule tyrosine kinase inhibitors), have been designed to
      inhibit the tyrosine kinase activity of the receptor, producing an anti-tumour
      effect. The development of surrogate markers to determine the drug activity of
      these new inhibitors would be of great benefit in drug evaluation and in the
      subsequent management of patient disease. This review describes current
      treatments of cancer using tyrosine kinase inhibitors and the use of proteomic
      analysis to identify possible markers of activity of these new drugs.

PMID- 14641097
TI  - On the structure of protein-protein interaction networks.
AB  - We present a simple model for the underlying structure of protein-protein
      pairwise interaction graphs that is based on the way in which proteins attach to
      each other in experiments such as yeast two-hybrid assays. We show that data on
      the interactions of human proteins lend support to this model. The frequency of
      the number of connections per protein under this model does not follow a power
      law, in contrast to the reported behaviour of data from large-scale yeast two
      hybrid screens of yeast protein-protein interactions. Sampling sub-graphs from
      the underlying graphs generated with our model, in a way analogous to the
      sampling performed in large-scale yeast two-hybrid searches, gives degree
      distributions that differ subtly from the power law and that fit the observed
      data better than the power law itself. Our results show that the observation of
      approximate power law behaviour in a sampled sub-graph does not imply that the
      underlying graph follows a power law.

PMID- 14641098
TI  - Supervised classification for gene network reconstruction.
AB  - One of the central problems of functional genomics is revealing gene expression
      networks - the relationships between genes that reflect observations of how the
      expression level of each gene affects those of others. Microarray data are
      currently a major source of information about the interplay of biochemical
      network participants in living cells. Various mathematical techniques, such as
      differential equations, Bayesian and Boolean models and several statistical
      methods, have been applied to expression data in attempts to extract the
      underlying knowledge. Unsupervised clustering methods are often considered as the
      necessary first step in visualization and analysis of the expression data. As for
      supervised classification, the problem mainly addressed so far has been how to
      find discriminative genes separating various samples or experimental conditions.
      Numerous methods have been applied to identify genes that help to predict
      treatment outcome or to confirm a diagnosis, as well as to identify primary
      elements of gene regulatory circuits. However, less attention has been devoted to
      using supervised learning to uncover relationships between genes and/or their
      products. To start filling this gap a machine-learning approach for gene networks
      reconstruction is described here. This approach is based on building classifiers-
      functions, which determine the state of a gene's transcription machinery through
      expression levels of other genes. The method can be applied to various cases
      where relationships between gene expression levels could be expected.

PMID- 14641099
TI  - Analysis and modelling of signal transduction pathways in systems biology.
AB  - There is general agreement that a systems approach is needed for a better
      understanding of causal and functional relationships that generate the dynamics
      of biological networks and pathways. These observations have been the basis for
      efforts to get the engineering and physical sciences involved in life sciences.
      The emergence of systems biology as a new area of research is evidence for these
      developments. Dynamic modelling and simulation of signal transduction pathways is
      an important theme in systems biology and is getting growing attention from
      researchers with an interest in the analysis of dynamic systems. This paper
      introduces systems biology in terms of the analysis and modelling of signal
      transduction pathways. Focusing on mathematical representations of cellular
      dynamics, a number of emerging challenges and perspectives are discussed.

PMID- 14641100
TI  - A probabilistic model for the extraction of expression levels from
      oligonucleotide arrays.
AB  - In this work we present a probabilistic model to estimate summaries of Affymetrix
      GeneChip probe level data. Comparisons with two different models were made both
      on a publicly available dataset and on a study performed in our laboratory,
      showing that our model performs better for consistency of fold change.

PMID- 14641101
TI  - Petri Net representations in systems biology.
AB  - The mathematical structures known as Petri Nets have recently become the focus of
      much research effort in both the structural and quantitative analysis of all
      kinds of biological networks. This review provides a very brief summary of these
      interesting new research directions.

PMID- 14641102
TI  - Reverse engineering of genetic networks with Bayesian networks.
AB  - This paper provides a brief introduction to learning Bayesian networks from gene
      expression data. The method is contrasted with other approaches to the reverse
      engineering of biochemical networks, and the Bayesian learning paradigm is
      briefly described. The article demonstrates an application to a simple synthetic
      toy problem and evaluates the inference performance in terms of ROC (receiver
      operator characteristic) curves.

PMID- 14641103
TI  - Reconstructing gene networks: what are the limits?
AB  - To fully realize the benefits of high-throughput post-genomic technologies it is
      necessary to reconstruct and analyse the complicated network of interactions
      through which most genes operate. We briefly summarize the mathematical
      frameworks that can be used to model such networks, and the types of algorithms
      available for their reconstruction. We then focus on dynamic models, typically
      described using differential equations, and explain the two main reconstruction
      approaches in current use. We discuss the data requirements of these algorithms
      and ask how well they correspond to current microarray data.

PMID- 14641104
TI  - Modelling the controls of the eukaryotic cell cycle.
AB  - The eukaryotic cell-division cycle is regulated by three modules that control
      G(1)/S, G(2)/M and meta/anaphase transitions. By using mathematical modelling, we
      show the dynamic characteristics of these individual modules and we also assemble
      them together into a comprehensive model of the eukaryotic cell-division cycle.
      With this comprehensive model, we also discuss the mechanisms by which different
      checkpoint pathways stabilize different cell-cycle states and inhibit the
      transitions that drive cell-cycle progression.

PMID- 14641105
TI  - Folic acid does not improve endothelial function in healthy hyperhomocysteinaemic
      subjects.
AB  - Folic acid supplementation lowers total plasma homocysteine (tHcy) and improves
      endothelial function in individuals with coronary artery disease (CAD) and in
      those with additional CAD risk factors. In the present study, we assessed whether
      endothelial function is impaired in healthy subjects with hyperhomocysteinaemia
      but without other CAD risk factors and whether folic acid supplementation
      improves endothelial function in these subjects. Flow-mediated dilatation (FMD)
      of the brachial artery was performed on 26 healthy subjects, age 49 +/- 2 years
      (mean +/- S.E.M.), with high tHcy (15.6 +/- 1.5 micromol/l) and 16 healthy age
      matched subjects with low tHcy (7.9 +/- 0.6 micromol/l; P < 0.001). Subjects with
      high tHcy were then randomized to receive 5 mg/day of folic acid or placebo for 8
      weeks in a double-blind cross-over trial with a 4-week washout. FMD was not
      associated with tHcy and was not different between high and low tHcy groups (7.0
      +/- 0.6% compared with 6.6 +/- 1.2%, P = 0.76). Treatment with folic acid
      decreased tHcy by 34% in hyperhomocysteinaemic subjects ( P = 0.02 compared with
      placebo), but had no effect on FMD (+ 0.5 +/- 0.6% compared with -0.7 +/- 0.5%; P
      = 0.17 compared with placebo). In healthy subjects with hyperhomocysteinaemia,
      but without additional cardiovascular risk, endothelial function is unimpaired
      and folic acid supplementation has no additional effect.

PMID- 14641106
TI  - Haemodynamic effects of hyperbaric hyperoxia in healthy volunteers: an
      echocardiographic and Doppler study.
AB  - In the present study, we observed the haemodynamic changes, using
      echocardiography and Doppler, in ten healthy volunteers during 6 h of compression
      in a hyperbaric chamber with a protocol designed to reproduce the conditions as
      near as possible to a real dive. Ambient pressure varied from 1.6 to 3 atm (1
      atm=101.325 kPa) and partial pressure of inspired O2 from 1.2 to 2.8 atm.
      Subjects performed periods of exercise with breathing through a closed-circuit
      self-contained underwater breathing apparatus (SCUBA). Subjects did not eat or
      drink during the study. Examinations were performed after 15 min and 5 h. After
      15 min, stroke volume (SV), left atrial (LA) diameter and left ventricular (LV)
      end-diastolic diameter (LVEDD) decreased. Heart rate (HR) and cardiac output (CO)
      did not vary, but indices of the LV systolic performance decreased by 10% and the
      LV meridional wall stress increased by 17%. After 5 h, although weight decreased,
      the serum protein concentration increased. Compared with values obtained after 15
      min, SV and CO decreased, but LV systolic performance, LA diameter, LVEDD and LV
      meridional wall stress remained unchanged. Compared with the reference values
      obtained at sea level, total arterial compliance decreased, HR remained unchanged
      and CO decreased. In conclusion, hyperbaric hyperoxia results in significant
      haemodynamic changes. Initially, hyperoxia and the SCUBA system are responsible
      for reducing LV preload, increasing LV afterload and decreasing LV systolic
      performance, although CO did not change. Prolonged exposure resulted in a further
      decrease in LV preload, because of dehydration, and in a further increase in LV
      afterload, due to systemic vasoconstriction, with the consequence of decreasing
      CO.

PMID- 14641108
TI  - Probing Zn2+-binding effects on the zinc-ribbon domain of human general
      transcription factor TFIIB.
AB  - The general transcription factor, TFIIB, plays an important role in the assembly
      of the pre-initiation complex. The N-terminal domain (NTD) of TFIIB contains a
      zinc-ribbon motif, which is responsible for the recruitment of RNA polymerase II
      and TFIIF to the core promoter region. Although zinc-ribbon motif structures of
      eukaryotic and archaeal TFIIBs have been reported previously, the structural role
      of Zn2 binding to TFIIB remains to be determined. In the present paper, we report
      NMR and biochemical studies of human TFIIB NTD, which characterize the structure
      and dynamics of the TFIIB Zn2-binding domain in both Zn2-bound and -free states.
      The NMR data show that, whereas the backbone fold of NTD is pre-formed in the apo
      state, Zn2 binding reduces backbone mobility in the b-turn (Arg28-Gly30), induces
      enhanced structural rigidity of the charged-cluster domain in the central linker
      region of TFIIB and appends a positive surface charge within the Zn2-binding
      site. V8 protease-sensitivity assays of full-length TFIIB support the Zn2
      dependent structural changes. These structural effects of Zn2 binding on TFIIB
      may have a critical role in interactions with its binding partners, such as the
      Rpb1 subunit of RNA polymerase II.

PMID- 14641107
TI  - A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95.
AB  - Using a yeast interaction screen to search for proteins that interact with cyclin
      D3 in thyroid gland, we identified the cAMP-dependent AKAP95 (protein kinase A
      anchoring protein 95). AKAP95 is a scaffolding protein that primarily co
      fractionates with the nuclear matrix, whereas a minor fraction associates with
      chromatin in interphase cells. In co-transfected Chinese-hamster ovary cells,
      AKAP95 strongly interacted with the three D-type cyclins, but not with CDK4
      (cyclin-dependent kinase 4) or with p27kip1. CDK4 displaced the interaction
      between cyclin D3 and AKAP95, suggesting that AKAP95 could not be the elusive
      bridging adaptor between D-type cyclins and CDK4 or play a role in the regulation
      of cyclin D3-CDK4 activity. Interaction between endogenous AKAP95 and cyclin D3
      or cyclin D1 was detected in canine thyrocytes, human fibroblasts and NIH-3T3
      cells. As both AKAP95 and cyclins D were recently reported to associate with
      minichromosome maintenance proteins [Eide, Tasken, Carlson, Williams, Jahnsen,
      Tasken and Collas (2003) J. Biol. Chem. 278, 26750-26756; Gladden and Diehl
      (2003) J. Biol. Chem. 278, 9754-9760], we hypothesize that the interaction
      between AKAP95 and D-type cyclins might serve to facilitate the emerging
      regulatory role of cyclin D-CDK4 in the formation of the prereplication complex
      at the DNA replication origins.

PMID- 14641109
TI  - The porcine taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21) gene:
      evolution by gene duplication and gene conversion.
AB  - Porcine taurochenodeoxycholic acid 6alpha-hydroxylase, cytochrome P450 4A21
      (CYP4A21), differs from other members of the CYP4A subfamily in terms of
      structural features and catalytic activity. CYP4A21 participates in the formation
      of hyocholic acid, a species-specific primary bile acid in the pig. The CYP4A21
      gene was investigated and found to be approx. 13 kb in size and split into 12
      exons. The intron-exon organization of the CYP4A21 gene corresponds to that of
      CYP4A fatty acid hydroxylase genes in other species. Comparison with a genomic
      segment of a pig CYP4A fatty acid hydroxylase gene ( CYP4A24 ) revealed a
      sequence identity with CYP4A21 that extends beyond the exons, indicating a common
      origin by gene duplication. A pronounced sequence identity was found also within
      the proximal 5'-flanking regions, whereas the patterns of mRNA expression of
      CYP4A21 and CYP4A fatty acid hydroxylases in pig liver differ. Sequence
      comparison aiming to elucidate the origin of the unique features of CYP4A21
      revealed a region of decreased sequence identity from exon 6 to exon 8, strongly
      suggesting that gene conversion could have contributed to the evolution of
      CYP4A21.

PMID- 14641110
TI  - Peroxisomal-proliferator-activated receptor alpha activates transcription of the
      rat hepatic malonyl-CoA decarboxylase gene: a key regulation of malonyl-CoA
      level.
AB  - MCD (malonyl-CoA decarboxylase), which catalyses decarboxylation of malonyl-CoA,
      is known to play an important role in the regulation of malonyl-CoA
      concentration. Recently, it has been observed that the expression of MCD is
      significantly decreased in the hearts of the PPARalpha (peroxisome-proliferator
      activated receptor alpha) (-/-) mice, where the rate of fatty-acid oxidation is
      decreased by the increased malonyl-CoA level [Campbell, Kozak, Wagner, Altarejos,
      Dyck, Belke, Severson, Kelly and Lopaschuk (2002) J. Biol. Chem. 277, 4098-4103].
      This suggests that MCD may be transcriptionally regulated by PPARalpha. To
      investigate whether PPARalpha is truly responsible for transcriptional regulation
      of the rat MCD gene, transient reporter assay was performed in CV-1 cells. The
      promoter activity was increased by 17-fold in CV-1 cells co-transfected with
      PPARalpha/retinoid X receptor alpha expression plasmid. In sequence analysis of
      the promoter region, three putative PPREs (PPAR response elements) were
      identified, and promoter deletion analysis showed that PPRE2 and PPRE3 were
      functional. Electrophoretic mobility-shift assays revealed that
      PPARalpha/retinoid X receptor alpha heterodimer indeed bound to the two PPREs,
      and the binding specificity of PPARalpha on PPRE was also confirmed by
      experiments with mutated oligonucleotides. These results indicate that the
      elements behaved as a responsive site to PPARalpha activation. MCD mRNA levels in
      WY14643-treated rat hepatoma cells as well as in the liver of fenofibrate-fed
      Otsuka Long-Evans Tokushima fatty rats were also found to be increased,
      suggesting that PPARalpha can activate the rat hepatic MCD transcription by
      binding to the PPREs in the promoter. We propose that MCD performs an important
      role in understanding the regulatory mechanism between activated PPARalpha and
      fatty-acid oxidation by altering the malonyl-CoA concentration.

PMID- 14641111
TI  - Superactivity and conformational changes on alpha-chymotrypsin upon interfacial
      binding to cationic micelles.
AB  - The catalytic behaviour of alpha-CT (alpha-chymotrypsin) is affected by cationic
      micelles of CTABr (hexadecyltrimethylammonium bromide). The enzyme-micelle
      interaction leads to an increase in both the V(max) and the affinity for the
      substrate p -nitrophenyl acetate, indicating higher catalytic efficiency for
      bound alpha-CT. The bell-shaped profile of alpha-CT activity with increasing
      CTABr concentrations suggests that the micelle-bound enzyme reacts with the free
      substrate. Although more active with CTABr micelles, the enzyme stability is
      essentially the same as observed in buffer only. Enzyme activation is accompanied
      by changes in alpha-CT conformation. Changes in tertiary structure were observed
      by the increase in intensity and the red shift in the alpha-CT tryptophan
      fluorescence spectrum, suggesting the annulment of internal quenching and a more
      polar location of tryptophan residues. Near-UV CD also indicated the transfer of
      aromatic residues to a more flexible environment. CTABr micelles also induces an
      increase in alpha-helix, as seen by far-UV CD and FTIR (Fourier-transform
      infrared) spectroscopies. The far-UV CD spectrum of alpha-CT shows an increase in
      the intensity of the positive band at 198 nm and in the negative band at 222 nm,
      indicating an increased alpha-helical content. This is in agreement with FTIR
      studies, where an increase in the band at 1655 cm(-1), corresponding to the alpha
      helix, was shown by fitting analysis and difference spectroscopy. Spectral
      deconvolution indicated a reduction in the beta-sheet content in micelle-bound
      alpha-CT. Our data suggest that the higher catalytic efficiency of micelle-bound
      alpha-CT results from significant conformational changes.

PMID- 14641112
TI  - Fructoselysine 3-epimerase, an enzyme involved in the metabolism of the unusual
      Amadori compound psicoselysine in Escherichia coli.
AB  - The frl (fructoselysine) operon encodes fructoselysine 6-kinase and
      fructoselysine 6-phosphate deglycase, allowing the conversion of fructoselysine
      into glucose 6-phosphate and lysine. We now show that a third enzyme encoded by
      this operon catalyses the metal-dependent reversible interconversion of
      fructoselysine with its C-3 epimer, psicoselysine. The enzyme can be easily
      assayed through the formation of tritiated water from [3-3H]fructoselysine.
      Psicoselysine supports the growth of Escherichia coli, causing the induction of
      the three enzymes of the frl operon. No growth on fructoselysine or psicoselysine
      was observed with Tn5 mutants in which the putative transporter (FrlA) or
      fructoselysine 6-phosphate deglycase (FrlB) had been inactivated, indicating the
      importance of the frl operon for the metabolism of both substrates. The ability
      of E. coli to grow on psicoselysine suggests the occurrence of this unusual
      Amadori compound in Nature.

PMID- 14641113
TI  - Nickel, chromium and cobalt in consumer products: revisiting safe levels in the
      new millennium.
AB  - The transition metals nickel (Ni), chromium (Cr) and cobalt (Co) are common
      causes of allergic contact dermatitis (ACD). Given the high frequency with which
      these allergens can be associated with hand eczema in those responsible for
      domestic work, it has been suggested that contamination of household consumer
      products with these metals may be of relevance to the causation/chronicity of
      hand dermatitis. Dose-response studies using 48 h occlusive patch test conditions
      in sensitized individuals show that >/=90% of sensitized patients fail to react
      below 1 p.p.m., even on irritated skin. Assessment under more realistic exposure
      conditions has shown that in the presence of irritants and/or following repeated
      exposures, such individuals rarely react to levels below 10 p.p.m. On the basis
      of this information, it was recommended a decade ago that household (and other
      consumer) products should not contain more than 5 p.p.m. of each of Ni, Cr or Co
      and that, for an even greater degree of protection, the ultimate target level
      should be 1 p.p.m. The data generated since the original recommendations were
      made serve to reinforce the validity of these recommendations. Indeed, it is our
      view that typically the level of each of these transition metals should not
      normally exceed 1 p.p.m. Then, where consumer products meet this guideline fully,
      modern quantitative risk assessment shows clearly that elicitation of ACD is
      highly improbable, and the chance of the induction of sensitization is even
      lower.

PMID- 14641114
TI  - A patch test study of 27 crude drugs commonly used in Chinese topical
      medicaments.
AB  - Chinese topical medicaments (CTMs) are commonly used in Taiwan and in Southeast
      Asia. However, a systematic evaluation of contact sensitization potential from
      CTM has not been carried out to our knowledge. This study was undertaken to
      investigate the incidence of contact sensitivity to the components of CTM in
      patients with contact dermatitis from CTM. A screening series of 27 crude drugs
      most commonly used in CTM as well as a modified European standard series was
      patch tested in 30 patients. The herbs with the most frequent positive reactions
      were Flos Caryophylli (see text), Radix Angelicae Pubescentis (see text), Cortex
      Cinnamomi (see text), Cortex Radix Acanthopanacis (see text), Caulis Impatientis
      (see text), Resina Draconis/Sanguis Draconis (see text), Fructus Cnidii (see
      text), Radix Gentiana Macrophyllae (see text), and Rhizoma Ligustici Chuanxiong
      (see text). Concomitant allergy to colophonium was found in most of these
      positive reactions. Reducing the concentration and simplifying the compositions
      of these components, as well as replacement with those of low allergenicity in
      CTM, such as Rhizoma Arisaematis (see text), Herba Lycopodii (see text), Radix
      Cyathulae Officinalis (see text), Rhizoma Pinelliae (see text), Radix Angelicae
      Dahuricae (see text), Herba Dendrobii (see text), Secretio Moschus (see text),
      and Stigmata Croci (see text), may be advocated. A precise labelling of the
      dosage of each component and the exact chemical compounds in CTM products could
      further improve the safety and therapeutic effects of CTM in the future.

PMID- 14641115
TI  - Patch testing with oxidized R-(+)-limonene and its hydroperoxide fraction.
AB  - R-(+)-Limonene is an ubiquitous allergen in our environment. It is one of the
      most widely used fragrance materials not only in fine fragrances but also most
      often incorporated in domestic and occupational products. Although the non
      oxidized R-(+)-limonene itself is not allergenic, it easily forms allergenic
      products due to autoxidation during handling and storage. 2273 patients at 4
      dermatological clinics in Europe were patch tested between 1997 and 1999 in 2
      steps. First, the oxidation mixture of R-(+)-limonene and 1 selected allergen
      fraction of the mixture, the limonene hydroperoxides, were tested in 2 different
      vehicles in consecutive patients. A diverging frequency of positive patch test
      reactions was observed in the 4 clinics. 3.8% of the consecutive patients tested
      reacted to oxidized R-(+)-limonene in 2 clinics, 6.5% in the 3rd, whereas 0.3% in
      the 4th clinic. In 2 of the centres, different but significant concomitant
      positive response rates to other allergens were observed; e.g. to fragrance
      materials and to colophonium. However, in the total test population, 57% of the
      limonene-allergic subjects did not react to any of the fragrance allergy markers
      used in the standard series. In the 2nd step, patients showing positive reactions
      were retested, also including additional separate allergens of the limonene
      oxidation mixture (carvone and limonene oxide). 60% of the limonene-allergic
      patients showed positive results at retesting. The limonene hydroperoxide
      fraction was proved to be the most important allergen of the oxidation mixture,
      showing positive reactions in around 60% of the limonene-allergic patients at
      both test sessions. Testing limonene oxide and carvone separately resulted in
      very few positive reactions. 3% oxidized R-(+)-limonene in non-stabilized
      petrolatum is most suitable when using only 1 test preparation for diagnosis of
      contact allergy to oxidized limonene. Our data give clinical support to the
      European classification of R-(+)-limonene, containing oxidation products, as a
      skin sensitizer.

PMID- 14641116
TI  - Specific immunoglobulin E in patients with immediate persulfate hypersensitivity.
AB  - Persulfate salts may cause contact urticaria, allergic and irritant contact
      dermatitis, rhinitis and asthma. The mechanism of the immediate reactions has
      been unclear. Positive prick test, skin application and nasal and bronchial
      provocations identify immediate allergy. There is only 1 previous report of
      specific binding of immunoglobulin E (IgE) to ammonium persulfate demonstrated by
      radioallergosorbent test (RAST). In the present study, fresh 2% ammonium and
      potassium persulfate solutions were used for prick testing. Patients with
      positive prick tests were further evaluated with open skin application,
      immunospot and RAST. Prick testing with persulfate salts was performed in a total
      of 138 patients. 7 patients had a positive reaction to at least 1 persulfate
      salt. 6 of the patients had had skin symptoms, urticaria, eczema or angioedema,
      because of contact with hair bleaches. Open application on healthy skin was
      performed in 4 patients, and 3 out of them had urticarial reactions. The sera of
      5 patients were investigated with immunospot and RAST. On immunospot, specific
      binding of IgE to human serum albumin (HSA)-conjugated ammonium and potassium
      persulfate was found in 2 patients. 1 immunospot-positive patient also had a
      positive RAST to ammonium persulfate-HSA conjugate. The mechanism of immediate
      hypersensitivity to persulfates thus seems to be IgE-mediated at least in some
      patients.

PMID- 14641117
TI  - Assessment of irritant skin reactions using electrical impedance--a comparison
      between 2 laboratories.
AB  - To assess interlaboratory variability in the measurement of skin electrical
      impedance (IMP), we evaluated irritant reactions to sodium lauryl sulfate (SLS)
      (2%) and nonanoic acid (NAA) (40%) in 2 laboratories. We studied the patch test
      responses in 40 healthy male and female volunteers between 20 and 30 years of age
      (20 in each laboratory) with an instrument for measuring IMP. 2 other
      bioengineering methods and visual scoring were also used to facilitate further
      illumination of any findings. A strict protocol including all details of the
      measurement procedure was carefully implemented in both laboratories. The skin
      reactions were evaluated at 23 h and at 3, 7 and 14 days after exposure. Our
      findings show that both irritants caused distinct dynamic responses detectable
      with the bioengineering techniques. Interestingly, the IMP baseline values varied
      between the 2 laboratories. Moreover, at early stages in the development of
      irritation (day 1), the irritants induced changes in IMP indices in the opposite
      direction, which accords with the concept of various IMP patterns of contact
      dermatitis caused by different irritants. Although the absolute values of IMP
      differed in both laboratories, the dynamic response patterns were the same.

PMID- 14641118
TI  - Citral a fragrance allergen and irritant.
AB  - Citral is a well known contact allergen and a contact irritant. Routine patch
      testing in the past may have been restricted because of possible irritant (IR)
      patch test responses. 586 consecutive patients, with hand eczema, were patch
      tested with a selection of fragrances including citral 2% petrolatum and the
      European standard series. 28 of the patients showed a positive patch test
      reaction (+ to +++) to citral and 82 at least 1 IR patch test reaction and no
      positive patch test reaction to citral. A statistically significant association
      between a positive patch test reaction to citral and positive patch test
      reactions to other fragrances compared with IR reactions (n = 82) was
      established. The difference regarding fragrance history found between those with
      IR and positive reactions to citral was not significant. Citral could be an
      allergen and/or irritant, worthy of further more extensive studies.

PMID- 14641119
TI  - Utility of historical vehicle-control data in the interpretation of the local
      lymph node assay.
AB  - The accepted approach to the interpretation of local lymph node assay (LLNA) data
      requires comparison of responses in the test groups with background activity
      found in concurrent vehicle-treated controls. However, of established value in
      the interpretation of toxicity test data is the use of historical control values
      that provide one criterion against which to judge the integrity of individual
      experiments. Specifically, the availability of robust and relevant historical
      control data permits examination of whether, in any individual experiment,
      control values fall within the expected range. With the most commonly used
      vehicle employed in the LLNA, acetone/olive oil (4 : 1) (v/v), the mean values,
      standard deviations and normal ranges are increasingly well established for a
      given laboratory, although there is some variation between laboratories,
      particularly with regard to expected ranges. Against this background, it is
      possible to identify (and, if appropriate, eliminate) a concurrent vehicle
      control value that falls well outside the expected range. To explore critically
      the potential merits of this approach, one specific example is examined in
      detail.

PMID- 14641120
TI  - Neutrophilic dermatosis of the dorsal hands elicited by thermal injury.

PMID- 14641121
TI  - Contact dermatitis from geraniol in washing-up liquid.

PMID- 14641122
TI  - Lichen nitidus-like allergic contact dermatitis - a clinicopathological study.

PMID- 14641123
TI  - Multiple contact allergens in a violinist.

PMID- 14641124
TI  - Near-fatal delayed hypersensitivity reaction to cloxacillin.

PMID- 14641125
TI  - Allergic contact dermatitis from a condensate of boric acid, monoethanolamine and
      fatty acids in a metalworking fluid.

PMID- 14641126
TI  - Allergic contact dermatitis due to glycyrrhizic acid as an ingredient of a hair
      restorer.

PMID- 14641128
TI  - Metamizole-induced acute generalized exanthematous pustulosis.

PMID- 14641127
TI  - Acute generalized exanthematous pustulosis induced by ranitidine hydrochloride.

PMID- 14641129
TI  - Pigmented contact cheilitis from ricinoleic acid in lipsticks.

PMID- 14641130
TI  - Contact allergy to various ingredients of topical medicaments.

PMID- 14641131
TI  - Systemic contact dermatitis from tamsulosin.

PMID- 14641132
TI  - Allergic contact dermatitis from rectified camphor oil in Earex ear drops.

PMID- 14641133
TI  - Corticosteroid cross-reactivity.

PMID- 14641135
TI  - The development of integrated haematopathology laboratories: a new approach to
      the diagnosis of leukaemia and lymphoma.
AB  - The diagnosis and monitoring of leukaemia and lymphoma requires the effective
      integration of a wide range of diagnostic techniques and expertise. The need to
      develop this type of service that crosses traditional boundaries of laboratory
      specialities is being recommended in national guidance. The Haematological
      Malignancy Diagnostic Service based within the Leeds Teaching Hospitals NHS Trust
      was established in 1993 to provide specialist laboratory services for the
      diagnosis of haematological malignancy for Yorkshire and Humberside in the UK.
      The department uses a wide range of methodologies including morphology,
      immunocytochemistry, flow cytometry and molecular genetics [fluorescent in situ
      hybridization (FISH) and polymerase chain reaction (PCR)] in a systematic and co
      ordinated way. We describe how the department was established, its current
      working practices and highlight the advantages of an integrated laboratory for
      diagnosis of tumours of the haematopoietic system.

PMID- 14641136
TI  - Haemoglobinometry in general practice.
AB  - Haemoglobinometry as a primary point-of-care test is well established. This study
      was undertaken to assess whether haemoglobinometry by itself provides an adequate
      haematological screening procedure in general practice. In a series of 500
      sequential blood counts received by the central hospital laboratory from local
      doctors, 405 (81%) had a normal haemoglobin. Full blood counts on these samples
      showed 15% with one or more blood count parameters outside 2SD of normal
      reference values, including increased MCV, low MCV with low MCH and MCHC,
      leucocytosis with neutrophilia, a few cases with neutropenia, lymphopenia,
      monocytosis or eosinophilia. When the limits were set at 3SD, these abnormalities
      were found in only 7.6% of the cases. Calculation of test utility gave a positive
      predictive value of 0.83, a negative predictive value of 0.85, with a likelihood
      ratio of 14.3 and an overall diagnostic reliability of 84%. It was concluded that
      haemoglobin alone is a valuable primary screening test and a full blood count is
      required only when anaemia is present or when the patient's history and clinical
      signs indicate the need for such further investigation. Using this protocol it is
      unlikely that any serious error will be made in diagnosing a clinically
      significant condition; the main limitation is failure to diagnose pre-anaemic
      iron deficiency.

PMID- 14641137
TI  - Immature granulocyte detection by the SE-9000 haematology analyser during
      pregnancy.
AB  - The objective of this study was to determine the nature of the alarm for immature
      granulocytes appearing in haemograms from pregnant women, as detected by the
      immature cell information channel (IMI) of the SE-9000 automated haematology
      analyser. Of all tests run on pregnant women in a 4-month period (n = 698), the
      first 100 haemograms with immature granulocyte alarms (14.33%) were collected.
      Each of these samples was then stained with Wright-Giemsa stain. The following
      variables were also analysed: age of the mother, trimester and days of gestation,
      type of delivery, weight and sex of the baby, and Apgar score. Most pregnant
      women were in the third trimester of gestation (82%) when an alarm was noted on
      the IMI channel. Of the patients, 62% had normal deliveries. The most frequent
      complication was obstructed delivery (23%). Mean percentages by microscopic
      counts of band cells, metamyelocytes, and myelocytes were 2.99, 0.45, and 0.19%,
      respectively. There was a statistically significant correlation for all cell
      types between the SE-9000 and the manual count method. No association was
      observed between the presence of immature granulocytes and the clinical variables
      analysed. The SE-9000 analyser shows high sensitivity in the IMI channel for
      detection of immature forms.

PMID- 14641138
TI  - Soluble transferrin receptor: a discriminating assay for iron deficiency.
AB  - The distinction between iron deficiency anaemia (IDA) and the anaemia that
      accompanies infection, inflammation or malignancy, commonly termed the anaemia of
      chronic disease (ACD), is often difficult, as the conventional laboratory indices
      of iron status are often influenced by acute phase responses. In recent years,
      the soluble transferrin receptor (sTfR) has been introduced as a sensitive, early
      and highly quantitative new marker of iron depletion, increasing in proportion to
      tissue iron deficit. Unlike conventional laboratory tests, the sTfR is not an
      acute phase reactant and remains normal in patients with chronic disease. In this
      study TfR concentrations were compared with the gold standard of iron stores,
      bone marrow iron. The sTfR concentration was shown to be the most efficient test
      in predicting bone marrow iron stores in 20 patients with ACD (75% efficiency)
      and in 18 patients with rheumatoid arthritis (RA) (94% efficiency). Measurement
      of sTfR may be a useful addition in the differential diagnosis of ACD and IDA.

PMID- 14641139
TI  - Rapid diagnosis of alpha(o)-thalassemia using the relative quantitative PCR and
      the dissociation curve analysis.
AB  - A method for diagnosis of alpha(o)-thalassemia was developed based on detection
      of accumulated PCR product using SYBR Green I, a double-stranded DNA binding dye,
      and a fluorescence-detecting thermocycler. Primers were designed to specifically
      amplify - -SEA and - -Thai deletions of alpha(o)-thalassemia. Albumin was
      selected as the reference gene. The comparative CT method was used to quantitate
      the target gene relative to the albumin gene. Dissociation curve analysis was
      used as a qualitative tool to distinguish different types of alpha(o)
      thalassemia. In this study, the melting temperatures of the - -Thai and - -SEA
      deletions were 83 and 86 degrees C, respectively. Application of the assay for
      the diagnosis of alpha(o)-thalassemia heterozygotes and homozygotes is reported.
      The assay is highly robust and amenable to high throughput. It is thus a useful
      tool for the rapid detection of alpha(o)-thalassemia in populations with a high
      frequency of alpha(o)-thalassemia, - -SEA and - -Thai deletions.

PMID- 14641140
TI  - Red cell osmotic fragility studies in hemoglobin C-beta thalassemia: osmotically
      resistant microspherocytes.
AB  - Typically certain features of red cell morphology predict the results of osmotic
      fragility testing. Microspherocytes generally have increased and target cells
      decreased fragility. Blood smears in homozygous hemoglobin C disease show an
      interesting admixture of microspherocytes and target cells. Yet osmotic fragility
      studies generally show only reduced fragility and no population of fragile cells
      to correspond with the spherocytes. The present study demonstrates that the red
      cells of patients with hemoglobin C-beta thalassemia share many characteristics
      with hemoglobin C red cells, including the decreased osmotic fragility of all
      cells despite the presence of both spherocytes and target cells. These
      paradoxically osmotically resistant spherocytes probably arise because of
      cellular dehydration due to a K-Cl transport system which may be activated by
      binding of hemoglobin C to the red cell membrane.

PMID- 14641141
TI  - Experience with eosin-5'-maleimide as a diagnostic tool for red cell membrane
      cytoskeleton disorders.
AB  - The diagnosis of hereditary spherocytosis (HS) is based on red cell morphology
      and other conventional tests such as osmotic fragility, autohemolysis and
      acidified glycerol lysis. However, milder cases are at times difficult to
      diagnose. Confirmation by red blood cell (RBC) membrane protein analysis is not
      possible in most laboratories. Recently, a flow cytometric method has been
      described for quantitating the fluorescence intensity of intact red cells after
      incubation with the dye eosin-5'-maleimide (EMA), which binds specifically to the
      anion transport protein (band-3) at lysine-430. This has been shown to be an
      effective screening test for red cell membrane disorders. We evaluated the
      usefulness of this approach for screening membrane protein disorders such as HS
      and hereditary elliptocytosis (HE) and its value in discriminating this group
      from other hemolytic anemias, such as glucose-6-phosphate dehydrogenase (G6PD)
      deficiency, beta-thalassemia trait, sickle cell anemia and autoimmune hemolytic
      anemia. Fluorescence intensity, expressed in mean channel fluorescence (MCF)
      units, was determined using a Becton Dickinson FACS Caliber flow cytometer.
      Membrane protein analysis was carried out by sodium dodecyl sulfate
      polyacrylamide gel eletrophoresis (SDS-PAGE). RBCs from patients with HS and HE
      gave significantly lower MCF values (P < 0.001) than the normal control group and
      other patient groups. The diagnosis of HS in four cases was confirmed by RBC
      membrane protein electrophoresis and all showed a deficiency of spectrin. The
      advantage of the EMA dye method are its specificity for membrane disorders, as
      well as being a simple, user-friendly and rapid method which is inexpensive,
      provided a flow cytometer is available.

PMID- 14641142
TI  - Subclassification of HbS syndrome: is it necessary?
AB  - Sickle beta-thalassaemia (S beta-thalassaemia) is a condition, which results from
      coinheritance of a sickle cell gene and a beta-thalassaemia gene. The clinical
      phenotype depends on the type of beta-thalassaemia gene (beta+ or beta(o)). There
      are several similarities in clinical and haematological features, which sometimes
      pose a difficulty in correct diagnosis. A definitive diagnosis is required in
      order to initiate early supportive treatment in patients with homozygous sickle
      cell disease (SS disease) and to define the later clinical course. Forty-seven
      cases of haemoglobin sickle syndrome (HbS syndrome) were studied. The clinico
      haematological features and high-performance liquid chromatography (HPLC) results
      from 17 patients with S beta-thalassaemia were compared with those of SS disease
      (10 patients). Splenomegaly was more commonly found in patients with S beta
      thalassaemia. Among the haematological features, red blood cell counts and HbA2
      levels were significantly higher in patients with S beta-thalassaemia, while red
      cell indices, such as MCV, MCH were significantly lower than those seen SS
      disease. MCHC, PCV total haemoglobin (Hb), HbS, A and HbF were similar in the two
      groups.

PMID- 14641143
TI  - Nonmyeloablative stem cell transplantation with fludarabine and cyclophosphamide
      for patients with hematologic malignancies.
AB  - We conducted a multi-center phase I/II trial of nonmyeloablative stem cell
      transplantation for patients with hematologic malignancies. The aim of this trial
      was to assess the safety and feasibility of this treatment modality for older or
      younger patients with significant organ dysfunction, who could not be treated
      with conventional high dose chemoradiotherapy. Twelve patients were treated with
      a conditioning regimen consisting of fludarabine and cyclophosphamide, followed
      by peripheral blood stem cell transplantation from human leukocyte antigen (HLA)
      identical siblings. Nonhematologic toxicities were mild. Median time to absolute
      neutrophils above 0.5 x 10(9)/l, 1.0 x 10(9)/l and platelets above 50 x 10(9)/l
      were 8, 10 and 12 days, respectively. Donor dominant hematopoiesis was achieved
      in all patients, with or without donor leukocyte infusion. The cumulative
      incidence of acute and chronic graft-versus-host disease (GVHD) was 75 and 56%,
      respectively. Only one patient experienced early death within 100 days, caused by
      acute GVHD complicated by fungal infection. All patients except one achieved
      complete remission. With a median follow-up of 330 days, expected progression
      free survival is 75%. Overall survival is 76%. Our study confirms that
      nonmyeloablative stem cell transplantation with cyclophosphamide and fludarabine
      conditioning is a safe and promising treatment for elderly patients with
      hematologic malignancies. A further study in large-scale setting is warranted.

PMID- 14641144
TI  - Adhesion molecule expression by bone marrow CD34-positive cells in aplastic
      anemia before and after immunosuppressive therapy.
AB  - Appropriate adhesion between bone marrow stem cells and the marrow
      microenvironment is necessary for hematopoiesis, since signals that promote
      maturation or apoptosis are transmitted from stromal cells to stem cells. In
      aplastic anemia (AA), interferon-gamma produced by stromal cells has more
      influence on the pathogenesis of marrow failure than interferon-gamma produced by
      lymphocytes. We evaluated the expression of cell adhesion molecules, such as very
      late antigen-4 (CD49d), and -5 (CD49e) or c-kit receptor (CD117), by CD34
      positive bone marrow cells in patients with AA who achieved hematological
      complete remission after immunosuppressive therapy. Before treatment, CD34
      positive cells showed markedly higher expression of CD49d and CD49e than cells
      from healthy controls, indicating the strong adhesion of stem cells to the bone
      marrow stroma. Expression of CD49d and CD49e was significantly decreased,
      reaching normal levels, after hematological recovery. These findings suggest that
      changes in adhesion molecule expression by stem cells are important in the
      pathology of AA.

PMID- 14641145
TI  - Echis time, under-carboxylated prothrombin and vitamin K status in intensive care
      patients.
AB  - Vitamin K deficiency is a known cause of coagulopathy in hospitalized patients,
      but the extent of the problem has not been well assessed. This noninterventional,
      prospective observational study of 35 adults was undertaken in the intensive care
      unit (ICU) and examined the incidence of and the methods for diagnosing vitamin K
      deficiency. Measurements of prothrombin time, Echis time and plasma
      concentrations of under-carboxylated prothrombin (proteins induced in vitamin K
      absence or antagonism, PIVKA-II), vitamin K1 and ferritin were made during the 48
      h after admission to the unit and repeated if coagulopathy developed later.
      Plasma vitamin K1 was low in 15 admissions (43%), in 11 cases of patients with
      coagulopathy and in four cases without coagulopathy. PIVKA-II was present in 12
      cases (34%), of whom four had low vitamin K1 levels. All of the eight patients
      with raised PIVKA-II but normal vitamin K concentration were hyperferritinaemic.
      We conclude that low plasma vitamin K levels, suggestive of low tissue stores,
      are common in intensive care patients with or without coagulopathy. As 34% of
      patients had a raised PIVKA-II, this suggests that vitamin K stores may be
      insufficient to maintain full gamma-carboxylation of prothrombin and emphasize
      the need to anticipate vitamin K deficiency in the ICU setting by appropriate
      supplementation.

PMID- 14641146
TI  - False positive Kleihauer tests and unnecessary administration of anti-D
      immunoglobulin.
AB  - This obstetric case shows two false negative Kleihauer tests and two persistently
      positive Kleihauer tests leading to unnecessary administration of anti-D
      immunoglobulin. A diagnosis of hereditary persistence foetal haemoglobin (HPFH)
      was only confirmed by access to flow cytometry making use of both anti-HbF and
      anti-D labels. The case highlights the importance of a high index of clinical
      suspicion for HPFH and the importance of access to flow cytometry estimation of
      minor RhD red cell populations postnatally in RhD-negative mothers.

PMID- 14641147
TI  - An interesting presentation of intrathoracic extramedullary hematopoiesis in a
      patient with thalassemia intermedia.
AB  - Extramedullary hematopoiesis (EMH) occurs as a compensatory mechanism for bone
      marrow dysfunction in severe thalassemia. In addition to the more common
      locations, such as liver, spleen and lymph nodes, a mass of EMH may occasionally
      occur in the thorax. Intrathoracic EMH is usually asymptomatic. A 69-year-old
      woman who initially presented with hematuria, dysuria, and left inguinal pain was
      found to have paravertebral masses in the thorax. Histopathologic examination of
      a CT-guided needle aspiration biopsy of the masses showed the presence of
      trilineage hematopoiesis. We present this unusual case, in which EMH was
      diagnosed by chance in an elderly patient with no symptoms related to
      thalassemia.

PMID- 14641148
TI  - Ethnic variation in von Willebrand factor levels can influence the diagnosis of
      von Willebrand disease.

PMID- 14641149
TI  - Age-related macular disease: an ongoing challenge.

PMID- 14641151
TI  - Iris colour, ethnic origin and progression of age-related macular degeneration.
AB  - AIM: To investigate the relationship between iris colour, ethnic origin and the
      progression of age-related macular degeneration (AMD). METHODS: Participants were
      recruited from the population-based Melbourne Visual Impairment Project or the
      prospective, randomized, double-masked Vitamin E, Cataract and Age-Related
      Macular Degeneration study. From these two cohorts, 171 participants aged between
      52 and 93 years who were identified as having early AMD features at their
      baseline examination (1992-1995) were followed for an average of 6.8 years (until
      2001) to determine the progression rate of early AMD. The participants' iris
      colour was categorized as light, intermediate or dark. Ethnic origin was
      categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants'
      grandparents' country of birth. RESULTS: In total, 53 (31%) of the 171
      participants showed signs of AMD progression. Participants with light iris colour
      had twofold the risk of AMD progression of those with dark or intermediate iris
      colours, although the age-adjusted and multivariate-adjusted associations were
      not significant (both P = 0.13). Age-adjusted and multivariate comparisons of
      Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable
      but non-significant association with progression of AMD (P= 0.22 and P= 0.14,
      respectively). CONCLUSION: Individuals with light iris colour or of Anglo-Saxon
      ethnic origin had a strong tendency to greater progression of AMD. A larger
      sample is required to confirm these clinically important, but statistically non
      significant, associations.

PMID- 14641152
TI  - Macular hole surgery with or without indocyanine green stained internal limiting
      membrane peeling.
AB  - BACKGROUND: To compare the anatomical and visual outcome in primary idiopathic
      macular hole surgery with or without indocyanine green (ICG) stained internal
      limiting membrane (ILM) peeling. METHODS: The medical records of the last 40
      consecutive eyes receiving primary idiopathic macular hole surgery with gas as
      internal tamponade performed by a single surgeon were retrospectively reviewed
      and analysed. All eyes had a follow-up period of at least 6 months. In the
      initial 22 consecutive eyes, no ILM peeling was performed (non-ILM peeling
      group). The subsequent 18 eyes underwent surgery with ICG-stained ILM peeling
      (ILM peeling group). RESULTS: The primary anatomical closure rates were 88.9% and
      59.1% in the ILM peeling group and non-ILM peeling group, respectively. The
      difference was statistically significant (Fisher's exact test, P = 0.038).
      Improvement in visual acuity was more marked in the ILM peeling group than in the
      non-ILM peeling group, with a mean improvement of 3.6 and 1.3 lines, respectively
      (two-tailed t-test, P = 0.036). There were significantly more cases with
      improvement of two or more lines of visual acuity after surgery, with 66.7% in
      the ILM peeling group and 31.8% non-ILM peeling group (Chi-square test P =
      0.028). However, there was no significant difference in the final postoperative
      logMAR best-corrected visual acuity between the two groups (two-tailed t-test, P
      = 0.073). CONCLUSIONS: Based on this study, ICG-stained ILM peeling seems to
      improve the anatomical and visual outcome in primary idiopathic macular hole
      surgery. Further studies in this aspect are warranted.

PMID- 14641153
TI  - Photodynamic therapy in practice: a review of the results of the first 12 months
      experience with verteporfin at the Royal Victorian Eye and Ear Hospital.
AB  - PURPOSE: To review the 12-month results of the first 136 eyes treated with
      photodynamic therapy (PDT) with verteporfin at a single institution, and to
      determine if this treatment when used in the broader community could reproduce
      the results achieved in the Treatment of Age-related Macular Degeneration (AMD)
      with PDT (TAP) study. METHODS: A record of all patients who first received PDT
      with verteporfin at The Royal Victorian Eye and Ear Hospital between the time of
      its introduction in February 2000 and February 2001 was prospectively maintained.
      The medical charts of these cases were reviewed and fluorescein angiograms were
      graded. Eyes with AMD were classified into three groups: TAP comparable if they
      had predominantly classic subfoveal choroidal neovascularization (CNV) and visual
      acuity between 6/12 and 6/60; VIP comparable if they had occult but no classic
      subfoveal CNV and visual acuity better than 6/36; and PDT ineligible if they fell
      outside recommended eligibility guidelines of the TAP/VIP studies. The main
      outcome measure was visual acuity change, with total number of treatments a
      secondary outcome variable. RESULTS: A total of 136 eyes of 130 patients began
      PDT during this period. The baseline angiogram and clinical data were available
      for 123 eyes (90%), and these were reviewed. Fourteen eyes had non-AMD related
      CNV, while 109 eyes of 105 patients had AMD. Of the 109 AMD related lesions, 72
      (66%) were TAP comparable, six (5.5%) were VIP comparable and 31 (28%) were PDT
      ineligible. At the 12-month visit the proportion of TAP comparable eyes with same
      or better vision was 36/72 (50%), compared to 13/31 (42%) of the PDT ineligible
      eyes (P = 0.45). Only 30/72 (42%) of the TAP comparable eyes were still
      undergoing regular angiographic and clinical assessment (similar to the TAP
      protocol) at the time of the 12 month visit. The number of these who had same or
      better vision at 12 months was 17/30 (57%) compared to 19/42 (44%) TAP comparable
      eyes without regular angiographic follow up to 12 months (P = 0.37).
      CONCLUSDIONS; When used according to the guidelines established by the TAP study,
      the visual acuity results with PDT approached those achieved in the TAP study.
      When eyes were either enrolled outside the TAP study eligibility guidelines, or
      were not actively followed up over the 12-month period as per TAP study
      guidelines, the visual outcome was similar to natural history of CNV secondary to
      AMD.

PMID- 14641154
TI  - Associations between glaucomatous visual field loss and participation in
      activities of daily living.
AB  - PURPOSE: This study investigated the association between visual field loss and
      participation in daily activities in individuals with glaucoma. METHODS: Seventy
      nine patients were recruited from the Royal Victorian Eye and Ear Hospital.
      Visual fields were assessed using the Esterman binocular visual field tests and
      participation in daily activities was assessed using the Impact of Vision
      Impairment (IVI) questionnaire. Visual acuity and contrast sensitivity were also
      measured. RESULTS: There was no independent relationship between visual field
      loss and IVI score (r = -0.20; P = 0.09), except for the mobility domain (r =
      0.25; P = 0.03). Mobility was the most affected domain of the IVI (mean = 1.2).
      Over a quarter of the patients reported experiencing moderate to severe
      restriction with mobility activities despite relatively minor binocular field
      loss. CONCLUSION: Mobility is the area in which glaucoma patients encounter
      difficulties even when the visual field and visual acuity are relatively good.
      Questions related to mobility could be asked to identify those patients who need
      rehabilitation.

PMID- 14641156
TI  - Corneal endothelial status in the subtypes of primary angle closure glaucoma.
AB  - PURPOSE: To study the corneal endothelium and pachymetry in eyes with different
      subtypes of primary angle closure glaucoma (PACG), as compared to controls.
      METHODS: A cross-sectional study was conducted on 30 consecutive patients in each
      subtype of PACG, subacute, acute and chronic, and 30 age and refraction matched
      controls. The parameters recorded included gonioscopy, optic disc evaluation,
      applanation tonometry, specular microscopy and central ultrasonic pachymetry.
      RESULTS: The mean endothelial cell counts in the four groups were as follows:
      subacute PACG 2396 +/- 271 cells/mm2, acute PACG 1597 +/- 653 cells/mm2, chronic
      PACG 2229 +/- 655 cells/mm2 and controls 2461 +/- 321 cells/mm2. The mean
      endothelial cell count in the fellow eyes of subacute PACG, acute PACG and
      chronic PACG patients was 2294 +/- 305 cells/mm2, 2388 +/- 226 cells/mm2 and 2108
      +/- 203 cells/mm2, respectively (NS). The acute PACG patients had significantly
      lower endothelial cell counts (P < 0.001) as compared to the other three groups.
      Eyes in which the acute attack of angle closure persisted for less than 72 h had
      a mean endothelial cell count of 2016 +/- 306 cells/mm2, as compared to 759 +/-
      94.4 cells/mm2 in eyes with an attack lasting for 72 h or more (P < 0.001). The
      endothelial count was also significantly lower in eyes with chronic PACG as
      compared to control eyes (P < 0.001). There was increased pleomorphism and
      polymegathism of the corneal endothelial cells seen in eyes with resolved acute
      and chronic PACG. The mean central corneal thickness was 531.4 +/- 25.3 microm in
      eyes with subacute PACG, 567.9 +/- 37.3 microm in eyes with acute PACG, 526.4 +/-
      31.9 microm in eyes with chronic PACG and 525 +/- 12.6 microm in control eyes.
      The acute PACG eyes had a significantly higher corneal thickness (P < 0.001) when
      compared to all the other groups. CONCLUSION: There is a significant decrease in
      the corneal endothelial cell density in eyes that have had an acute attack of
      angle closure glaucoma and in eyes with chronic PACG. The endothelial cell
      population in eyes with sub-acute PACG and in the fellow eyes of all subtypes of
      PACG is not significantly different from the normal population.

PMID- 14641155
TI  - Long-term efficacy of mycophenolate mofetil in the control of severe intraocular
      inflammation.
AB  - PURPOSE: To assess whether the previously demonstrated short-term efficacy of the
      immunosuppressant mycophenolate mofetil (MMF; CellCept, Roche) is maintained in
      the long-term management of refractory uveitis. METHODS: The study was an open
      label, non-comparative retrospective series of 14 patients with refractory
      uveitis and treated with MMF for a mean of >33 months. Mycophenolate mofetil was
      given at a dosage of 1 g (oral) twice daily. Indications included prednisolone
      reduction, additive agent with cyclosporin, or replacement therapy (azathioprine
      or methotrexate). The intraocular inflammatory response, side-effects, and
      toxicity were monitored. RESULTS: Intraocular inflammation remained under control
      in 10 patients, unchanged in three and deteriorated in one patient. Transient
      side-effects included tiredness, headache and dizziness (one patient each,
      lasting less than 2 weeks from the time of MMF introduction). Mycophenolate
      mofetil was stopped in one patient because of absence of prolonged clinical
      improvement. Vision improved in 25% (7 eyes), did not change in 50% (14 eyes),
      but was reduced in 25% (7 eyes). CONCLUSIONS: Mycophenolate mofetil is safe for
      long-term usage and is recommended for treatment of refractory panuveitis or
      posterior uveitis with uncontrolled inflammation despite high prednisolone
      maintenance dosage (>15 mg/day) or toxicity or lack of efficacy of other immuno
      suppressive agents. However, MMF is less effective for refractory uveitis
      unresponsive to azathioprine.

PMID- 14641157
TI  - Prescribing trends in infectious keratitis: a survey of New Zealand
      ophthalmologists.
AB  - PURPOSE: To obtain an overview of the treatment of infectious diseases of the
      cornea by New Zealand ophthalmologists and to analyse the data in the context of
      evidence-based treatment recommendations. METHODS: A questionnaire was sent to
      all New Zealand ophthalmologists. It comprised 23 multiple-choice questions
      pertaining to the characteristics of the respondents, the nature of their
      practice and their prescribing preferences in infectious conjunctivitis and
      keratitis. RESULTS: Of the 93 ophthalmologists surveyed, 80.6% returned the
      questionnaire. Of those in clinical practice, 91.4% regularly treated patients
      with corneal disease. A subspecialty interest in cornea was stated by 12.5% of
      these. This paper reports observations for adenoviral conjunctivitis and
      adenoviral, Herpes simplex, varicella zoster, bacterial, acanthamoebal and fungal
      keratitis. In some conditions prescribing practice varied dramatically, such as
      in adenoviral conjunctivitis where 50% of respondents prescribed a corticosteroid
      and 51.6% an antibiotic, whereas 37.5% prescribed only lubrication or no topical
      treatment. In other conditions there was a high degree of agreement between
      ophthalmologists; indeed, all ophthalmologists treated Herpes simplex dendritic
      keratitis with topical acyclovir. No statistically significant differences in
      prescribing habits were identified between subspecialist and non-subspecialist
      groups, although some important clinical differences emerged. There were
      occasional marked differences in response when the age group of respondents was
      considered, particularly in relation to the management of adenoviral infections
      and bacterial keratitis. CONCLUSIONS: The findings of this survey suggest that
      the majority of New Zealand ophthalmologists generally follow international
      guidelines for the management of infectious keratitis. The identified variations
      in management provide a foundation for informed clinical debate and the
      development of treatment guidelines, in line with evidence-based recommendations.

PMID- 14641158
TI  - Serum melatonin levels following enucleation and transpupillary thermotherapy in
      patients with choroidal melanoma.
AB  - PURPOSE: To study serum melatonin levels in patients with choroidal melanoma
      preoperatively and following enucleation and transpupillary thermotherapy.
      METHODS: Forty patients with preoperative choroidal melanoma were included in the
      study. Of these, 15 patients underwent enucleation (group 1) and 25 patients
      received transpupillary thermotherapy (group 2). A further 20 patients without
      melanoma acted as age-matched controls. Serum melatonin levels were determined 1
      day preoperatively, and at the first and sixth months postoperatively using
      ELISA. RESULTS: Preoperative serum melatonin levels were highest in group 2
      followed by group 1, but this was not statistically significant compared to
      controls. Postoperatively, a constant decrease of serum melatonin was observed in
      both groups after the first month, which reached statistical significance at the
      sixth month (P = 0.003). Also, a significant regression in tumour thickness was
      documented in group 2 (P = 0.003). Three patients in group 1 developed hepatic
      metastases. CONCLUSIONS: Patients with choroidal melanomas had higher levels of
      serum melatonin compared to individuals without tumours. Smaller tumours were
      associated with more elevated melatonin levels compared to larger tumours. Serum
      melatonin levels fell considerably following enucleation and transpupillary
      thermotherapy.

PMID- 14641159
TI  - Three horizontal muscle squint surgery for large angle infantile esotropia.
AB  - BACKGROUND: To report the long-term outcome of a series of 49 patients who
      underwent three horizontal muscle squint surgery for large angle infantile
      esotropia. METHODS; The patient records were retrospectively reviewed of 49 (24
      girls [49%], 25 boys) consecutive patients with infantile esotropia of angle > or
      =60 Delta, who had undergone three horizontal muscle surgery performed by one
      surgeon (author GG). Surgery consisted of bilateral medial rectus recession
      combined with graded unilateral lateral rectus resection. Surgeries were carried
      out over a 6-year period with a mean follow-up period of 32.9 months (3.7-71.8
      months). RESULTS: Using Kaplan-Meier life-table analysis, cumulative surgical
      success (orthotropia +/-10 Delta) was 93.9% at 1 week, 91.8% at 2 and 6 months,
      87.7% at 12 and 18 months, 79.9% at 2 years, 77.1% at 3, 4 and 5 years, and 70.6%
      at 6 years. The mean preoperative deviation was 68.7 Delta. The mean age at
      surgery was 12.9 months. The failure rate was independent of preoperative
      deviation. Prevalence of residual esotropia (>10 Delta) varied from 2.0% at 1
      week to 17.0% at 6 years. Similarly the prevalence of consecutive exotropia (>10
      Delta) varied from 4.0% at 1 week to 12.4% at 6 years. CONCLUSION; Operating in a
      graded fashion on three horizontal muscles in children with large angle infantile
      esotropia has a high success rate, even over long-term follow up. Based on the
      study's results, amounts of surgery for a given angle of strabismus are proposed.

PMID- 14641161
TI  - Measurement of the economic impact of visual impairment from age-related macular
      degeneration in Australia.
AB  - The purpose of this report was to: (i) outline the potential value of health
      economic studies into age-related macular degeneration (AMD); (ii) provide an
      overview of health economic studies pertinent to AMD; and (iii) outline the basic
      frame work of cost-of-illness studies (a useful first step in applying economic
      methods). The detection and management of sensory loss in the elderly plays a key
      role in the Australian Government's Healthy Ageing Strategy. Age-related macular
      degeneration is currently the leading cause of blindness in elderly Australians.
      Although a large proportion of AMD cases remain untreatable, the introduction of
      photo-dynamic therapy provides a relatively expensive and possibly cost-effective
      innovation for others. Antioxidant therapy has also been proven effective in
      reducing progression of early to late disease. The discipline of economics can
      contribute to an understanding of AMD prevention and treatment through: (i)
      describing the current burden of disease; (ii) predicting the changes in the
      burden of disease over time, and (iii) evaluating the efficiency of different
      interventions. Cost-of-illness studies have been performed in many fields of
      medicine. Little work, however, has been done on describing the economic impact
      from AMD. A number of different economic evaluation methods can be used in
      judging the efficiency of possible interventions to reduce the disease burden of
      AMD. Although complementary in nature, each has specific uses and limitations.
      Studies of the economic impact of eye diseases are both feasible and necessary
      for informed health care decision-making.

PMID- 14641160
TI  - In vivo effects of fluoroquinolones on rabbit corneas.
AB  - PURPOSE: The use of topical fluoroquinolones to treat microbial keratitis is
      associated with an increased incidence of corneal perforation compared to other
      standard treatments. This study examined the effects of topical fluoro-quinolones
      on corneal collagen and keratocytes in intact rabbit corneas and corneas with an
      epithelial defect. METHODS: Studies consisted of one group of intact corneas and
      one group of corneas where a 6-mm epithelial defect was created with a surgical
      scrape. Within each group, eyes were randomly assigned to one of four topical
      medications (0.3% ciprofloxacin, 0.3% ofloxacin, fortified antibiotics (1.36%
      tobramycin, 5% cefrazolin) or Tears Naturale (Alcon Laboratories, Frenchs Forest,
      NSW, Australia). Two drops were instilled hourly for 48 h and then 2-hourly for
      an additional 48 h. At 96 h the corneas were removed and processed for light
      microscopy, immunohistology for collagen IV, V and VI, and apoptosis staining.
      RESULTS: In intact rabbit corneas there was no demonstrable difference between
      treatment groups. In corneas with an epithelial defect, both fluoroquinolones
      delayed epithelial healing when compared to fortified antibiotics or tears.
      Keratocyte loss was seen in all groups and was greatest in the ofloxacin group.
      Median stromal thickness with keratocyte loss were: ofloxacin 30%; ciprofloxacin
      10%; fortified antibiotics 7.5%; and tears 15% (ofloxacin vs tears, Mann-Whitney
      = 16.0, P = 0.09). Keratocyte loss did not correlate with the amount of
      demonstrable apoptosis. Collagens IV, V and VI showed no differences between
      treatments. CONCLUSIONS: These results suggest that ofloxacin is potentially
      cytotoxic to corneal keratocytes. Such an effect could lead to the observed
      increased incidence of corneal perforation in microbial keratitis.

PMID- 14641163
TI  - Thioridazine retinopathy.

PMID- 14641164
TI  - Idiopathic polypoidal choroidal vasculopathy in a Caucasian man: problems of
      diagnosis and treatment.

PMID- 14641165
TI  - A large macular hole in a young patient with Best's disease.

PMID- 14641166
TI  - Splendore-Hoeppli phenomenon causing ptosis.

PMID- 14641167
TI  - Visual loss in a patient with lamotrigine-induced cicatrizing conjunctivitis.

PMID- 14641168
TI  - Trends in beta irradiation for pterygium in Queensland.

PMID- 14641169
TI  - Cataract and naturopathic remedies.

PMID- 14641171
TI  - Breaking the species barrier: use of SCID mouse-human chimeras for the study of
      human infectious diseases.
AB  - Mouse-human chimeras have become a novel way to model the interactions between
      microbial pathogens and human cells, tissues or organs. Diseases studied with
      human xenografts in severe combined immunodeficient (SCID) mice include
      Pseudomonas aeruginosa infection in cystic fibrosis, group A streptococci and
      impetigo, bacillary and amoebic dysentery, and AIDS. In many cases, disease in
      the human xenograft appears to accurately reproduce the disease in humans,
      providing a powerful model for identifying virulence factors, host responses to
      infection and the effects of specific interventions on disease. In this review,
      we summarize recent studies that have used mouse-human chimeras to understand the
      pathophysiology of specific bacterial and protozoan infections.

PMID- 14641172
TI  - Genome sequencing and comparative genomics of tropical disease pathogens.
AB  - The sequencing of eukaryotic genomes has lagged behind sequencing of organisms in
      the other domains of life, archae and bacteria, primarily due to their greater
      size and complexity. With recent advances in high-throughput technologies such as
      robotics and improved computational resources, the number of eukaryotic genome
      sequencing projects has increased significantly. Among these are a number of
      sequencing projects of tropical pathogens of medical and veterinary importance,
      many of which are responsible for causing widespread morbidity and mortality in
      peoples of developing countries. Uncovering the complete gene complement of these
      organisms is proving to be of immense value in the development of novel methods
      of parasite control, such as antiparasitic drugs and vaccines, as well as the
      development of new diagnostic tools. Combining pathogen genome sequences with the
      host and vector genome sequences is promising to be a robust method for the
      identification of host-pathogen interactions. Finally, comparative sequencing of
      related species, especially of organisms used as model systems in the study of
      the disease, is beginning to realize its potential in the identification of
      genes, and the evolutionary forces that shape the genes, that are involved in
      evasion of the host immune response.

PMID- 14641173
TI  - Drosophila S2 cells: an alternative infection model for Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive facultative intracellular bacterial
      pathogen that infects humans and animals. Its pathogenic strategy involves the
      expression of virulence proteins that mediate intracytosolic growth and cell-to
      cell spread. A key virulence protein is the cholesterol-dependent cytolysin,
      listeriolysin O (LLO), which is largely responsible for mediating escape from the
      phagosome into the host cytosol. To study further the host processes exploited
      during L. monocytogenes infection, we sought to develop Drosophila S2 cells as a
      model for infection. Here, we show that S2 cells share a number of properties
      with mammalian cell culture models of infection. As with mouse macrophages, LLO
      was required for phagosomal escape from S2 cells. Furthermore, vacuolar escape
      was dependent on their acidification via the ATPase proton pumps, as bafilomycin
      A1 treatment sharply decreased escape. However, unlike in mouse macrophages, LLO
      mutants replicated in the phagosome of S2 cells. Drosophila cells are cholesterol
      auxotrophs, and exogenous cholesterol increased the infection rate of L.
      monocytogenes (LLO independent) and also augmented the efficiency of vacuolar
      escape (LLO dependent). With available genetic tools such as RNA interference, S2
      cells could become an important model in the study of host-pathogen interactions.

PMID- 14641174
TI  - Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is
      independent of the bacterial vacA and cag status.
AB  - Following reports that a VacA+cag+ toxigenic but not a VacA-cag- non-toxigenic
      Helicobacter pylori strain induced homotypic phagosome fusion in murine
      macrophages, we addressed that phenomenon in human cells. Mononuclear phagocytes
      and epitheloid cells were challenged with H. pylori strains of different vacA and
      cag genotypes and with VacA- and Cag- isogenic mutants, and chased in the absence
      or presence of signal transduction modulators. Electron microscopy revealed that,
      in monocytes: (i) homotypic phagosome fusion was frequently induced by all live
      H. pylori strains investigated but not by exogenous VacA; (ii) phagosomes
      containing bacteria fused, but not those containing latex beads; (iii) fusion
      resulted in communal compartments resembling giant multivesicular bodies; and
      (iv) formation of these compartments was blocked by inhibiting the host cell
      regulators PI 3-kinase, phospholipase C and p42 MAP kinase. Whereas some
      internalized bacteria remained viable 1 h after uptake, none survived a 24 h
      period. In contrast to monocytes, infected epitheloid cells rarely developed
      communal compartments. In combination, these results demonstrate that, in human
      monocytes, the H. pylori-induced homotypic phagosome fusion depends on neither
      the vacuolating cytotoxin VacA nor the cag pathogenicity island of H. pylori and
      does not result in prolonged intracellular survival.

PMID- 14641175
TI  - Exploration of host-pathogen interactions using Listeria monocytogenes and
      Drosophila melanogaster.
AB  - The facultative intracellular bacterial pathogen Listeria monocytogenes is
      capable of replicating within a broad range of host cell types and host species.
      We report here the establishment of the fruit fly Drosophila melanogaster as a
      new model host for the exploration of L. monocytogenes pathogenesis and host
      response to infection. Listeria monocytogenes was capable of establishing lethal
      infections in adult fruit flies and larvae with extensive bacterial replication
      occurring before host death. Bacteria were found in the cytosol of insect
      phagocytic cells, and were capable of directing host cell actin polymerization.
      Bacterial gene products necessary for intracellular replication and cell-to-cell
      spread within mammalian cells were similarly found to be required within insect
      cells, and although previous work has suggested that L. monocytogenes virulence
      gene expression requires temperatures above 30 degrees C, bacteria within insect
      cells were found to express virulence determinants at 25 degrees C. Mutant
      strains of Drosophila that were compromised for innate immune responses
      demonstrated increased susceptibility to L. monocytogenes infection. These data
      indicate L. monocytogenes infection of fruit flies shares numerous features of
      mammalian infection, and thus that Drosophila has the potential to serve as a
      genetically tractable host system that will facilitate the analysis of host
      cellular responses to L. monocytogenes infection.

PMID- 14641176
TI  - Role of macrophage phospholipase D in natural and CpG-induced antimycobacterial
      activity.
AB  - The present study addresses the differential ability of macrophages to control
      intracellular growth of non-pathogenic Mycobacterium smegmatis (Msm) and
      pathogenic M. tuberculosis (MTB). Results reported herein show that 3 h post
      infection, intracellular Msm, but not MTB, was significantly killed by
      macrophages. As the role of human macrophage phospholipase D (PLD) in the
      activation of antimicrobial mechanisms has been documented, we hypothesised the
      role of such enzyme in antimycobacterial mechanisms. To this aim, macrophage PLD
      activity was analysed at different times after exposure with either pathogenic
      MTB or non-pathogenic Msm. Results showed that, starting from 15 min after
      mycobacterial exposure, MTB did not induce macrophage PLD activity, whereas the
      environmental non-pathogenic Msm stably increased it. The direct contribution of
      PLD in intracellular mycobacterial killing was also analysed by inhibiting
      enzymatic activity with ethanol or calphostin C. Results show that PLD inhibition
      significantly increases intracellular Msm replication. In order to see whether
      the innate PLD-mediated antimicrobial mechanisms against MTB are also induced
      after CpG ODN stimulation, the role of PLD has been analysed in the course of CpG
      mediated intracellular MTB killing. CpG DNA increased PLD activity in both
      uninfected and MTB-infected macrophages, and the inhibition of PLD activity
      resulted in a significant reduction of CpG-induced MTB killing. Taken together,
      our data suggest a relationship between host PLD activation and the macrophage
      ability to control intracellular mycobacterial growth.

PMID- 14641177
TI  - BFA-sensitive and insensitive exocytic pathways in Entamoeba histolytica
      trophozoites: their relationship to pathogenesis.
AB  - Entamoeba histolytica manifests its pathogenicity through several cellular
      processes triggered by external stimuli that activate signal transduction
      pathways. The intense secretory activity resulting from stimulation is not
      correlated with a typical endoplasmic reticulum (ER) or Golgi organization, and
      little is known in this parasite about endocytic/exocytic pathways. The
      interactions of trophozoites with fibronectin (FN) and cultured mammalian cells,
      which elicit secretory activities, were chosen to study mechanisms that regulate
      cytoplamic traffic. Results showed that Brefeldin A (BFA) induced redistribution
      of the vesicular network recognized by antibodies against amoebic proteins PDI
      and ERD2. Furthermore, BFA diminished traffic to the plasma membrane of the beta1
      integrin-like FN receptor and the heavy subunit of the Gal/GalNAc lectin,
      required for adhesion to FN and target cells, respectively. However, BFA did not
      prevent thiol-proteinase secretion or inhibit the traffic of de novo synthesized
      proteinases. These data suggest that two distinct transport systems occur in E.
      histolytica, one similar to classical membrane protein transport and another
      independent of BFA and inducible by external stimuli. Actin-myosin contractility
      of the cortical cytoskeleton seems necessary for the final release of exported
      proteinases and the proper function of the surface proteins involved in adhesion.

PMID- 14641178
TI  - Intracellular activities of Salmonella enterica in murine dendritic cells.
AB  - Dendritic cells (DC) efficiently phagocytose invading bacteria, but fail to kill
      intracellular pathogens such as Salmonella enterica serovar Typhimurium (S.
      Typhimurium). We analysed the intracellular fate of Salmonella in murine bone
      marrow-derived DC (BM-DC). The intracellular proliferation and subcellular
      localization were investigated for wild-type S. Typhimurium and mutants deficient
      in Salmonella pathogenicity island 2 (SPI2), a complex virulence factor that is
      essential for systemic infections in the murine model and intracellular survival
      and replication in macrophages. Using a segregative plasmid to monitor
      intracellular cell division, we observed that, in BM-DC, S. Typhimurium
      represents a static, non-dividing population. In BM-DC, S. Typhimurium resides in
      a membrane-bound compartment that has acquired late endosomal markers. However,
      these bacteria respond to intracellular stimuli, because induction of SPI2 genes
      was observed. S. Typhimurium within DC are also able to translocate a virulence
      protein into their host cells. SPI2 function was not required for intracellular
      survival in DC, but we observed that the maturation of the Salmonella-containing
      vesicle is different in DC infected with wild-type bacteria and a strain
      deficient in SPI2. Our observations indicate that S. Typhimurium in DC are able
      to modify normal processes of their host cells.

PMID- 14641179
TI  - TashHN, a Theileria annulata encoded protein transported to the host nucleus
      displays an association with attenuation of parasite differentiation.
AB  - The intracellular apicomplexan parasite, Theileria annulata, manipulates its
      bovine host cell by over-riding the cells natural apoptotic response and inducing
      proliferation of the infected leukocyte. We have recently identified a T.
      annulata encoded family of polypeptides (TashATs) with characteristics that
      indicate that they are involved in control of host cell gene expression. Here we
      present data on another member of this family, TashHN, showing that it is located
      to the parasite and host cell nucleus. Immunoblot analysis demonstrated that,
      unlike TashAT2 and 3, TashHN displays three forms, the largest of which is
      enriched in the host nuclear fraction and appears to be phosphorylated. Northern
      and 5 prime race analyses identified multiple TashHN RNA species in infected
      cells that have retained the ability to differentiate. These transcripts showed
      subtly different kinetics, but all decreased during differentiation to the
      merozite, and two showed reduced levels prior to down-regulation of the other
      TashATs. In addition, analyses of multiple cell lines that have become severely
      attenuated in their potential to differentiate, indicated a substantial increase
      in TashHN expression, with host nuclear reactivity particularly enhanced.

PMID- 14641180
TI  - Activation of NF-kappaB and IL-8 by Yersinia enterocolitica invasin protein is
      conferred by engagement of Rac1 and MAP kinase cascades.
AB  - Yersinia enterocolitica triggers activation of the nuclear factor (NF)-kappaB and
      production of the proinflammatory chemokine interleukin (IL)-8 in intestinal
      epithelial cells. This activation is due to adhesion of the bacteria via their
      outer membrane protein invasin to the host cells. Using Clostridium difficile
      toxins that specifically inactivate small GTPases, and transfection of inhibitory
      proteins of the Rho-GTPases, we demonstrate that Rac1, but not Cdc42 or Rho, is
      required for activation of NF-kappaB by invasin. Invasin activated the mitogen
      activated protein kinases (MAPK) p38 and c-Jun N-terminal protein kinase (JNK)
      but not extracellular signal regulated kinase (ERK). The functional relevance of
      these pathways for invasin-mediated IL-8 expression was assessed by protein
      kinase inhibitors and dominant-negative kinase mutants. While NF-kappaB and JNK
      contribute to IL-8 transcription, p38 MAPK also acts through stabilization of IL
      8 mRNA, as confirmed by quantitative RT-PCR and electrophoretic mobility shift
      assays. Transfection experiments with I-kappaB kinase (IKK)1 and IKK2 mutants
      indicate that the release of NF-kappaB from its cytoplasmic inhibitor I-kappaB
      and its translocation into the nucleus is mediated by these kinases. Our data
      identify Rac1 as a key intermediate in invasin-triggered IL-8 synthesis and
      demonstrate that maximum IL-8 induction involves several MAP kinase cascades.

PMID- 14641181
TI  - BopB is a type III secreted protein in Bordetella bronchiseptica and is required
      for cytotoxicity against cultured mammalian cells.
AB  - The cytotoxicity of Bordetella bronchiseptica to infected cells is known to be
      dependent on a B. bronchiseptica type III secretion system. Although the precise
      mechanism of the type III secretion system is unknown, BopN, BopD and Bsp22 have
      been identified as type III secreted proteins. In order to identify other
      proteins secreted via the type III secretion machinery in Bordetella, a type III
      mutant was generated, and its secretion profile was compared with that of the
      wild-type strain. The results showed that the wild-type strain, but not the type
      III mutant, secreted a 40-kDa protein into the culture supernatant. This protein
      was identified as BopB by the analysis of its N-terminal amino acid sequence.
      Severe cytotoxicity such as necrosis was induced in L2 cells by infection with
      the wild-type B. bronchiseptica. In contrast, this effect was not observed by the
      BopB mutant infection. The haemolytic activity of the BopB mutant was greatly
      impaired compared with that of the wild-type strain. The results of a digitonin
      assay strongly suggested that BopB was translocated into HeLa cells infected with
      the wild-type strain. Taken together, our results demonstrate that Bordetella
      secretes BopB via a type III secretion system during infection. BopB may play a
      role in the formation of pores in the host plasma membrane which serve as a
      conduit for the translocation of effector proteins into host cells.

PMID- 14641183
TI  - Paediatric radiotherapy in Australia and New Zealand: an anachronism in 2003?
AB  - This report reviews the activities of the Paediatric Special Interest Group of
      the Royal Australian and New Zealand College of Radiologists in terms of its
      involvement with the Australian and New Zealand Children's Cancer Study Group and
      its research and educational activities. Examples of when and how radiotherapy is
      currently used in the management of paediatric malignancies are provided. Some
      thoughts for the future of both paediatric radiotherapy and our subspecialty are
      also presented.

PMID- 14641184
TI  - A 5-year audit of 778 neonatal renal scans (Part 1): perplexing pyelectasis and
      suggested protocol for investigation.
AB  - In this 5-year review of 778 neonatal renal scans seen in an Obstetric Hospital,
      most infants were referred because of antenatal ultrasound findings, 92% with
      fetal pyelectasis. The results were classified according to the ultrasound
      findings. The majority of neonates (76%) had a normal postnatal scan. A number
      had vesicoureteric reflux (VUR) found on a micturating cystourethrogram.
      Persistant mild to moderate pyelectasis or hydronephrosis (15%) proved to be a
      normal variant in many infants, but had a similar appearance to those with an
      early obstructive cause (1%). Pyelectasis has proved to be a poor predictor of
      VUR. A protocol outlining paediatric management for neonates with persisting
      pyelectasis is included. There were 59 infants (8%) with a miscellaneous group of
      renal anomalies, many with a characteristic antenatal ultrasound appearance
      suggesting the diagnosis. These infants have been separately reported and
      illustrated (Part 2). Overall, 13% of infants were found to have significant
      findings of obstruction, VUR or miscellaneous anomalies affecting management.

PMID- 14641185
TI  - A 5-year audit of 778 neonatal renal scans (Part 2). Miscellaneous anomalies in
      59 infants: a pictorial presentation.
AB  - In this 5-year review of 778 neonatal renal scans seen in an obstetric hospital,
      Mercy Hospital for Women, Melbourne, most infants were referred because of
      antenatal ultrasound findings. Ninety-two percent of these had fetal pyelectasis.
      The results were classified on the ultrasound findings. The majority of neonates
      (76%) had a normal postnatal scan. A number had vesicoureteric reflux found on
      micturating cystourethrogram. Persisting mild/moderate pyelectasis or
      hydronephrosis (15%) proved to be a normal variant in many infants, but had a
      similar appearance to those with an early obstructive cause (1%). There were 59
      infants (8%) with a miscellaneous group of renal anomalies, many with a
      characteristic antenatal ultrasound appearance suggesting the diagnosis. Review
      of these 59 infants illustrates the anomalies seen and reports the associated
      investigations and subsequent outcome in most cases.

PMID- 14641186
TI  - Acute contrast reaction management by radiologists: a local audit study.
AB  - Consultant radiologists and trainees must possess knowledge of optimal acute
      management of anaphylactic/anaphylactoid contrast reactions because patient
      survival depends upon prompt initial management. The aim of the present study is
      to assess the knowledge of first-line management of these reactions among
      radiologists. Within one working day, and without prior knowledge, radiology
      consultants and trainees within four teaching hospitals in a major Australian
      capital city were asked to complete a confidential questionnaire regarding acute
      resuscitation management. Scenarios were presented of an adult who developed life
      threatening symptoms of anaphylaxis immediately after intravenous contrast
      administration, ventricular fibrillation and profound bradycardia. Questions were
      asked with regards to adrenaline, corticosteroid, antihistamines, intravenous
      volume expansion, cardio-pulmonary rescuscitation and knowledge of the emergency
      telephone number. Sites were assessed for presence of an anaphylaxis management
      chart and also when each participant last completed a resuscitation course. Forty
      two participants were recruited. Overall, 53% of questions were answered
      correctly. Only 43% knew the adrenaline dose and if an incorrect dose was
      administered it was more likely to be an overdose. Notable inadequacies were also
      discovered with corticosteroid, atropine, antihistamine doses and intravenous
      fluid use. Only 26% had completed a resuscitation course in the past 2 years.
      Forty-five percent knew the emergency telephone number and 55% of rooms using
      intravenous contrast contained an immediately visible chart for contrast reaction
      management. Radiologist and trainee knowledge of immediate life-threatening
      contrast reaction management is deficient. Severe contrast reactions are uncommon
      with today's use of non-ionic contrast, but they still occur. Experience in the
      management of anaphylaxis can only come from regular, compulsory training.

PMID- 14641187
TI  - Cranial CT interpretation by senior emergency department staff.
AB  - The aims of the present study were to determine the rate of misinterpretation of
      non-contrast cranial CT scans by emergency specialists and trainees compared with
      specialist radiologists, and the proportion of misinterpretations that is
      consequential. A 12-month prospective blinded cohort study was performed. One
      hundred and ninety of 1,282 scans (14.8%) were misinterpreted, and 78 of these
      (41.1%) were of potential or actual consequence. We conclude that the performance
      of senior emergency department staff in non-contrast cranial CT interpretation is
      no better than moderately good, and a large proportion of misinterpretations are
      of potential or actual clinical consequence.

PMID- 14641188
TI  - Perianal infections: reader agreement and diagnostic performance of fat
      suppressed contrast-enhanced MRI.
AB  - We aimed to determine the diagnostic performance of the contrast-enhanced fat
      suppression technique in the detectability of perianal infections and to compare
      this technique with different MR sequences used for this purpose. Thirty
      consecutive patients with clinically suspected anorectal infections were examined
      with fast spin-echo (FSE) T2-weighted, short-inversion-time inversion recovery
      (STIR), and fat-suppressed and non-fat-suppressed T1-weighted spoiled gradient
      echo (SGE) (in-phase) dynamic contrast-enhanced sequences. The results of MRI
      were correlated with the findings of surgery, which was considered as the
      standard of reference. Receiver-operating-characteristic curves were
      reconstructed to describe and compare the diagnostic value of each MR technique.
      The values of kappa were used as a measure of observer reliability. Diagnostic
      performances of STIR, FSE T2-weighted and fat-suppressed and non-fat-suppressed,
      contrast-enhanced SGE T1-weighted techniques showed statistically insignificant
      differences in detection of perianal infections. There was almost perfect
      interobserver agreement regarding the presence of lesions on each MR technique.
      Fat-suppressed, contrast-enhanced SGE T1-weighted MRI showed adequate diagnostic
      performance in the detection of perianal infections. However, its significance is
      not different from the other MR sequences used for the present study.

PMID- 14641189
TI  - Skull fracture as a herald of intracranial abnormality in children with mild head
      injury: is there a role for skull radiographs?
AB  - The aim of the present study is to assess if skull fracture is a useful predictor
      of intracranial abnormality in children with minor head injury (MHI) and to
      evaluate the usefulness of skull radiographs. Retrospective review of CT scans
      and skull X-rays (SXR) of children <14 years of age with blunt head injury and
      correlation with the Glascow Coma Score definition of MHI (GCS > 12/15 or > 9/11)
      over a 1-year period was done. Three-hundred and eighty-one patients were
      included with a mean age of 6 years. Thirty-one percent of patients had
      intracranial abnormality. Forty-nine percent of all patients had fractures either
      on CT or SXR and 49% of these had intracranial abnormality on CT. Eighty-five
      percent of patients with drainable collections had associated fractures. Twenty
      three percent of MHI had abnormalities on CT, of which 32% were drainable
      collections. All patients with MHI who had drainable collections showed a
      fracture. Some protocols for paediatric head injury recommend CT for all patients
      while others rely on clinical indicators. In developing countries, CT is neither
      widely available nor accessible, and preselection of patients is necessary. We
      demonstrated that omitting CT in MHI could result in missed intracranial
      abnormalities. All MHI with drainable collections had fractures. Fractures
      identified on SXR can be added to the clinical indications for CT in MHI and can
      improve detection of 'silent' drainable collections.

PMID- 14641190
TI  - MRI and preoperative embolization of a nasal cavity haemangioma in a child.
AB  - Haemangiomas are common benign tumours of the head and neck region in children.
      The nasal cavity, however, is an extremely rare site for such lesions in
      childhood. We present the typical MRI features of a nasal cavity haemangioma in a
      12-year-old girl. Biopsy was avoided because of the MRI diagnosis and
      preoperative embolization of the mass was performed.

PMID- 14641191
TI  - Ultrasonic fetal weight estimation and tolerance to measurement error: a
      comparative analysis.
AB  - The objective of the present study was to test the hypothesis that volumetric
      formulae for fetal weight estimation are more tolerant to measurement error than
      exponential models. A mathematical model of normal fetal growth was constructed,
      using published British reference standards for biometric variables. Observed
      measurements were computer-generated by contaminating reference measurements with
      error terms according to their published coefficients of variation. The error in
      weight estimation was computed as the percentage difference between weight
      estimates derived from the observed biometric variables and the true
      measurements. A total of nine weight estimation formulae were tested. Campbell's
      formula appeared to be most affected by observational errors, especially before
      38 weeks. In this range, they varied up to 9%. The most tolerant was Shepard's
      formula, with errors of only approximately 2.8%. Other formulae showed errors of
      approximately 5-6%. With the exception of Campbell's formula, the effect of
      gestational age was minimal. There was no correlation between percentage error
      and fetal size. Combining ultrasound biometric variables into a fetal weight
      estimate does not always exaggerate the errors of the original measurements.
      There were no significant differences between volumetric and exponential
      formulae.

PMID- 14641192
TI  - Role of radiology in the treatment of malignant hilar biliary strictures 2: 10
      years of single-institution experience with percutaneous treatment.
AB  - We reviewed the results of percutaneous intervention of hilar biliary malignancy
      over a 10-year period at a single institution: the Royal Melbourne Hospital.
      Ninety-nine patients (100 treated in total) were included. Information was
      retrieved by retrospective examination of patient notes and radiology, combined
      with interviews with family and relevant physicians. Sixty-nine patients were
      treated with insertion of semipermanent stents, 19 had external drain tubes, and
      25 received percutaneous access for Iridium brachytherapy. Adequate drainage was
      achieved in 87% of the patients stented, and percutaneous access was successful
      in 96% of patients planned for brachytherapy. Of those patients undergoing
      endoprosthesis insertion, early complications occurred in 39% and late
      complications in 23%. Average survival for the entire patient population was
      227.3 days, with a median of 167 days. Longer survival times (213 vs 142 days)
      and lower complication rates (44 vs 64%) are observed with metal stents in
      comparison with plastic stents. Percutaneous intervention is an important
      treatment option in hilar biliary malignancy, particularly in patients unfit for
      surgery. Reasonable survival with good palliation is the most common outcome, and
      most patients do not require further intervention.

PMID- 14641193
TI  - Mammographic features of breast cancer in young symptomatic women.
AB  - The present study provides a descriptive analysis of the mammographic appearance
      of breast cancer in women aged 30-39 years presenting with symptoms, based on 65
      cancers confirmed with histology. We correlate the findings with clinical
      presentation and histological findings. We describe, categorize and illustrate
      the different lesions seen on mammography. Our study shows that
      microcalcification, with or without associated masses, is a dominant feature of
      breast cancer visualized on mammography in women in this age group.

PMID- 14641194
TI  - Views of Australian and New Zealand radiation oncologists and registrars about
      evidence-based medicine and their access to Internet based sources of evidence.
AB  - In order to determine the views of Australian and New Zealand (ANZ) radiation
      oncologists and registrars about evidence-based medicine (EBM) and their access
      to, and use of, Internet-based EBM resources such as MEDLINE and the Cochrane
      Library, a self-administered postal survey was sent out in December 2000. A total
      of 191 of 243 practicing ANZ radiation radiation oncologists (138) and registrars
      (53) responded (78.6% response rate). The main outcome measures were: (i) views
      about EBM and its promotion; (ii) previous EBM training; (iii) extent of Internet
      access and level of MEDLINE use and access to online medical journals; (iv)
      awareness of the Cochrane Library and other EBM resources; and (v) self
      assessment of common EBM technical terms. The results of the survey found that
      most (82.7%) indicated a positive view of themselves towards the current
      promotion of EBM. However, significantly fewer perceived their colleagues were as
      positive (chi2 = 35.2, d.f. = 1, P < 0.001). Most (84.8%) considered research
      findings 'useful' in day-to-day management of patients. The majority (70.2%) of
      respondents never had attended an EBM course; however, most indicated interest in
      such training. The majority (73.8%) reported having accessed MEDLINE or another
      bibliographic database in the previous month. Seventy-seven respondents (40.3%)
      reported that, in the past month, a literature search/article had influenced
      their practice. Only a minority (28.3%) used the Cochrane Library. Self
      assessment of most of the 12 EBM terms was generally high. For radiation
      oncologists, past attendance at an EBM course was significantly associated with a
      better overall self-assessment of these 12 terms (chi2 = 10.59, d.f. = 1, P =
      0.001). These findings reveal strong support for EBM among ANZ radiation
      oncologists and registrars with most regularly accessing the Internet for
      evidence. However, lack of awareness of some relevant EBM related resources,
      particularly the Cochrane Library, remains a challenge. Our findings invite a
      concerted effort by those promoting EBM to ensure clinicians have both the skills
      and knowledge to practice EBM.

PMID- 14641195
TI  - Type of consent does not influence patient recall of serious potential radiation
      toxicity of adjuvant breast radiotherapy.
AB  - In a sample of 174 women who had received verbal consent (n = 35), general
      written consent (n = 34) or detailed toxicity-specific written consent (n = 105),
      no significant differences were found in recall of serious potential toxicities
      by consent type. Age younger than 70 years and employment outside of the home
      were significantly associated with better recall. Factors not significantly
      associated with different recall rates were work status, use of interpreters for
      consent, time elapsed from treatment or the extent of radiotherapy (tangents only
      vs other). Overall recall was poor. Twenty-eight percent of women could not
      correctly recall if their treatment risked any of four nominated complications
      (lymphoedema, pneumonitis, rib fracture or brachial plexopathy). Significant
      numbers of women erroneously attributed a number of 'complications' or symptoms
      to radiotherapy.

PMID- 14641196
TI  - Australian prostate-specific antigen outcome and toxicity following radiation
      therapy for localized prostate cancer.
AB  - The objective of the present study was to examine prostate-specific antigen
      relapse free survival (PSA-RFS) and morbidity following 'conventional' radical
      radiation therapy for prostate cancer in two Australian regional treatment
      services. Four hundred and eighty men with clinically localized prostate cancer
      were treated between 1993 and 1997 at Liverpool and Westmead Hospitals using a
      standardized 4-field, CT-planned radiotherapy technique. Principal endpoints were
      PSA-RFS (American Society for Therapeutic Radiology and Oncology guidelines
      definition) and late rectal and urinary morbidity (Radiation Therapy Oncology
      Group/European Organisation for Research and Treatment of Cancer criteria). The
      median follow up of patients from the end of RT was 55 months. Prospectively,
      they were divided into three prognostic categories: (i) high risk T3 or 4 and/or
      PSA > 20 ng/mL and/or Gleason score 8-10 (40% of cohort); (ii) intermediate risk
      T1 or 2 and PSA 10-20 ng/mL and/or Gleason score 7 (33% of cohort); and (iii) low
      risk T1 or 2 and PSA < 10 ng/mL and Gleason score < 6 (27% of cohort). The 5-year
      actuarial PSA-RFS was 53% for the whole patient group. The 4-year rates were 32,
      56 and 75% for high, intermediate and low risk groups, respectively. On
      multivariate analysis, T-stage, Gleason score, pre-RT-PSA were strong independent
      predictors of PSA-defined outcome. Late (grade 2) rectal and urinary morbidity
      occurred at some point in time in the post-RT period in 8.0 and 5.8% of patients,
      respectively. These results confirm that low Gleason score, low T stage,
      presenting PSA < 10 ng/mL and nadir < 1 ng/mL remain the strongest predictors of
      a good outcome. Long-term toxicity was very acceptable. However, further
      improvement in outcome is desirable, and with the adoption of new technology
      allowing escalation of radiotherapy doses such an expectation might be achieved.

PMID- 14641197
TI  - How safe is Australian radiotherapy?
AB  - Many incidents and near-incidents are known to occur in Australian radiation
      oncology departments. The vast majority of incidents are minor in nature;
      however, a small percentage represent major threats to good patient care,
      administrative structures and public confidence. A small, but regular, number of
      incidents result in ad hoc local and/or state committees of enquiry or tort
      actions, and inevitably have substantial personal and departmental repercussions.
      Apart from some local databases on treatment-delivery incidents maintained by
      radiation therapists, no systematic data collection or analysis of treatment
      incidents exists for radiation oncology in Australia. The present paper argues
      the case for a prospective, systematic approach to the recording and analysis of
      treatment-related incidents and near incidents. Major barriers to such a scheme,
      including fear of litigation, misuse of information and lack of understanding on
      the nature of an incident are discussed.

PMID- 14641198
TI  - Cystosarcoma phyllodes: our institutional experience.
AB  - Twenty-six patients of Cystosarcoma phyllodes, treated between July 1994 and July
      2001, were analysed retrospectively. Median age at presentation was 38 years
      (range 13-61 years). Mean size of the lesion was 6 cm. There were 77% left-sided
      lesions and 23% right-sided lesions. Histologically, 58% lesions were benign, 11%
      borderline and 31% malignant lesions. All patients underwent definitive surgical
      procedure in the form of wide local excision or mastectomy. Four patients
      received postoperative radiotherapy. Median follow-up period was 35 months. Six
      patients showed recurrence, and four of these were malignant. Median disease-free
      survival period was 34 months.

PMID- 14641199
TI  - Hemimegalencephaly with tuberous sclerosis: a longitudinal imaging study.
AB  - Hemimegalencephaly is a rare cerebral malformation characterized by asymmetry of
      the hemispheres and cortical dysplasias. We report clinical and imaging findings
      in a child with hemimegalencephaly involving the right cerebral hemisphere with
      associated manifestations of tuberous sclerosis complex. Gross abnormal
      myelination pattern and gyral abnormalities were seen in the enlarged hemisphere.
      Subsequent scans showed atrophy of the frontoparietal region in the enlarged
      hemisphere and normal growth of the opposite hemisphere exceeding the size of the
      abnormal hemisphere in the frontoparietal region. A few white-matter lesions that
      were seen in the normal hemisphere on neonatal scan were difficult to appreciate
      on subsequent MR studies. The white-matter lesions were better seen in the
      neonatal period, whereas cortical tubers were better detected at a later age.

PMID- 14641200
TI  - Extramedullary fat fluid level on MRI as a specific sign for osteomyelitis.
AB  - The role of MR in the early diagnosis of acute osteomyelitis is well known. In
      the context of florid cellulitis, abnormalities of marrow signal are not
      uncommon, although they are often non-specific. Marrow oedema and enhancement in
      the context of deep cellulitis might reflect either reactive marrow oedema or
      true osteomyelitis. More specific signs lend favour to the diagnosis of
      osteomyelitis: these include focal bone destruction, periosteal reaction and
      sequestra. The observation of an extramedullary fat-fluid sign is also a specific
      sign for osteomyelitis, as illustrated in the following case report. This sign is
      an indication of cortical breach and, thus, in the setting of infection and in
      the absence of trauma confirms the presence of osteomyelitis. To our knowledge,
      this additional specific sign of osteomyelitis has not been previously reported
      on MR.

PMID- 14641201
TI  - Unsuspected bilateral central acetabular fractures diagnosed with nuclear
      scintigraphy.
AB  - Unsuspected bilateral undisplaced acetabular fractures were diagnosed on a three
      phase bone scan in a patient unable to weight-bear after an epileptic seizure.

PMID- 14641202
TI  - Small bowel CT fat density target sign in chronic radiation enteritis.
AB  - On CT, a thickened intestinal wall configured with a middle layer of low
      attenuation surrounded on each side by layers of higher attenuation has been
      termed the target sign. The presence of fat within the submucosal layer of the
      small intestine is a well-known manifestation of Crohn's disease, but has not
      been reported in other chronic intestinal diseases. We describe CT findings of
      fat density target sign in a patient with prior radiation.

PMID- 14641203
TI  - Follicular lymphoid hyperplasia simulating intussusception in a 6-year-old boy:
      clinical, radiological and histopathological findings.
AB  - We report the case of a 6-year-old boy who initially presented with recurrent
      abdominal pain. Diagnostic imaging, including ultrasound and CT, showed findings
      typical of an ileocecal intussusception with abdominal lymphadenopathy.
      Sonographically, the morphological appearance of the intussusception did not
      change during a 4-week follow-up period. Surgery was performed on the tentative
      diagnosis of a tumour versus lymphoma. Upon laparatomy, intussusception was ruled
      out and a large, broad-based tumour of the caecum was palpable. The
      histopathology after ileocecal resection revealed follicular lymphoid
      hyperplasia. Where there is radiological suspicion of an intussusception in
      children with no or insignificant symptoms, follicular lymphoid hyperplasia
      should be included in the differential diagnosis.

PMID- 14641204
TI  - Endovascular treatment for bilateral vertebral arteriovenous fistulas in
      neurofibromatosis 1.
AB  - We report a rare case of a 36-year-old woman with neurofibromatosis 1 (NF1) with
      bilateral vertebro-vertebral arteriovenous fistulas. The patient presented with
      quadriparesis and had neck pain. Angiography revealed vertebral arteriovenous
      fistulas bilaterally with dilated epidural venous plexuses compressing the
      cervical cord resulting in quadriparesis. Endovascular treatment using coils and
      balloons resulted in successful occlusion of both fistulas. At 6-months
      postembolization, the patient had improved significantly and is now able to walk
      with support.

PMID- 14641205
TI  - Isolated intrapetrous carotid canal atraumatic internal carotid artery
      dissection: MRI and digital subtraction angiography findings.
AB  - A case of spontaneous internal carotid artery (ICA) dissection confined to the
      intrapetrous carotid canal that was confirmed by angiography and magnetic
      resonance imaging is presented. Isolated dissection involving the intrapetrous
      ICA is rare; however, whenever arterial dissection is a consideration, specific
      review of imaging in this region is warranted.

PMID- 14641206
TI  - Intractable massive ascites following radical gastrectomy, treatment with local
      intraperitoneal administration of OK-432 using a unified CT and fluoroscopy
      system.
AB  - The case of a patient who developed intractable massive ascites caused by hepatic
      lymphorrhea derived from surgical injury to the hepatoduodenal ligament is
      presented. OK-432 was injected intraperitoneally through a catheter advanced to
      near the hepatoduodenal ligament, so as to expose this site to a high
      concentration of OK-432. Under ultrasound guidance, it was difficult to reach
      this site due to massive ascites, and so we performed this procedure under CT and
      fluoroscopic guidance using a unified CT and angiography system. Subsequently,
      local administration of OK-432 on five separate occasions resulted in resolution
      of the ascites. We ascribe this favourable result to the use of this unified CT
      and angiography system to advance the catheter to the suitable site, making
      possible the local administration of OK-432.

PMID- 14641207
TI  - Atrial septal aneurysm: MRI and echocardiography correlation.
AB  - A case of a patient with atrial septal aneurysm with findings in echocardiography
      and MRI is described.

PMID- 14641208
TI  - Anomalous communication of external carotid and vertebral arteries with
      associated intracranial parenchymal arteriovenous malformation: magnetic
      resonance angiography and angiographic findings.
AB  - A case of anomalous communication of the external carotid and vertebral arteries
      via a pro-atlantal intersegmental artery (PIA) with an associated intracranial
      parenchymal arteriovenous malformation (AVM) is presented. The course of the PIA
      is displayed by both conventional catheter angiography and by MR angiography
      (MRA). To our knowledge, neither an associated intracranial parenchymal AVM nor
      depiction of this congenital anomaly on MRA has been previously described. We
      also briefly review the embryology and anatomy of this anomaly.

PMID- 14641209
TI  - Subperiosteal aneurysmal bone cyst with associated bone marrow oedema: an unusual
      appearance.
AB  - A case of a subperiosteal aneurysmal bone cyst with adjacent bone marrow oedema
      is presented. Aneurysmal bone cysts have been well documented in the published
      literature; however, relatively few have been observed in a subperiosteal
      location, and associated bone marrow oedema in the absence of a demonstrable
      pathological fracture is a rare finding. Aneursymal bone cyst should be
      considered in the differential diagnosis of subperiosteal bone lesions and may be
      associated with bone marrow oedema.

PMID- 14641216
TI  - Bonded training places: evidence-based policy or a stab in the dark?

PMID- 14641217
TI  - Cognitive behavioural therapy: a study of rural general practitioners'
      understanding and expectations.
AB  - INTRODUCTION: Cognitive behavioural therapy (CBT) has been extensively used to
      manage depression and anxiety. It has been offered to general practitioners (GPs)
      as a technique suited to primary care. METHODS AND RESULTS: Forty-two GPs, who
      had participated in workshops on CBT, in rural Victoria, were surveyed about
      their use, expectations and understanding of CBT. Most of the GPs either
      occasionally or regularly used CBT. Respondents expressed concern that CBT would
      lengthen their consultations, while recognising its usefulness in their practice
      and capacity to enhance doctor-patient communication. CONCLUSIONS: The GPs in
      this study, while regarding CBT as an appropriate technique in general practice,
      expressed both broad outcome expectations from its use and concerns about its
      time management impact. This study indicates the need for further research on the
      role of CBT in rural general practice.

PMID- 14641218
TI  - Removing the roadblocks to medical and health student training in rural hospitals
      in Victoria.
AB  - OBJECTIVE: To assess the extent of undergraduate health student placements in
      regional hospitals in northern Victoria in 1999, prior to substantial changes in
      rural undergraduate medical education in Australia. METHOD: Cross sectional
      postal survey with telephone follow-up in north-east Victoria. Subjects were all
      17 regional and rural hospitals involved in health student teaching in North-east
      Victoria. Main outcome measures were the numbers, duration and discipline of
      health students placements and reported barriers to such placements. RESULTS:
      Large regional hospitals accounted for two-thirds of all undergraduate health
      student placements. Smaller sites placed few allied health students. Barriers to
      a larger, more sustainable system of rural placements and rotations included
      accommodation shortages and funding constraints, particularly in smaller rural
      hospitals. CONCLUSIONS: Adequate resourcing of placements of a meaningful
      duration, stronger institutional support, and improved resourcing of regional
      accommodation is required to facilitate a larger, more systematic and sustainable
      system of medical and health student placements in rural areas.

PMID- 14641219
TI  - Screening for diabetic retinopathy in remote Australia: a program description and
      evaluation of a devolved model.
AB  - OBJECTIVES: To describe the diabetic retinopathy screening program operating in
      the Kimberley and evaluate recruitment into and the quality and timeliness of,
      the screening procedure. METHOD: Review of the documents relating to the
      Kimberley diabetic retinopathy screening program and analysis of Kimberley
      diabetic retinopathy screening database. RESULTS: The Kimberley Public Health
      Unit developed and maintains a program of training, credentialing and ongoing
      professional development for retinal camera practitioners and a Kimberley-wide
      database of retinal photographs taken for diabetic retinopathy screening. As a
      result of this program, diabetic retinopathy screening is available in or close
      to most diabetics' home towns/communities and 58% had undergone retinopathy
      screening in the preceding 2 years. Over 90% of sets of photographs were of
      excellent or adequate quality. There was a positive relationship between
      credentialing and photograph quality and timeliness of photographs being sent
      away for reporting. CONCLUSIONS: Quality diabetic retinopathy screening, at
      prevalences comparable to, or higher than, other urban and rural populations, can
      be achieved in a remote area.

PMID- 14641220
TI  - Rural general practitioner experience of work-related violence in australia.
AB  - AIMS: To identify prevalence, precipitants and risk factors of violence and
      aggression towards Australian rural general practitioners (GPs). METHOD: Six
      focus groups were held with GPs from rural Western Australia and from two rural
      Divisions of General Practice in New South Wales and Victoria. A questionnaire
      was developed and all GPs in these three geographical areas were surveyed.
      RESULTS: The survey results showed that 73% of respondents had experienced some
      form of violent or aggressive behaviour from patients and 20% had been subjected
      to physical abuse during their careers as rural doctors. Physical abuse mostly
      occurred after hours and in a hospital or multipurpose centre. Violence and
      aggression were often associated with patient drug and alcohol intoxication and
      psychological disorders. CONCLUSION: Workplace violence and aggression against
      rural GPs is a frequent problem. Adequate funding and safe facilities for after
      hours care and training for GPs in managing dangerous situations should be
      provided.

PMID- 14641221
TI  - Rural general practitioner apprehension about work related violence in australia.
AB  - AIMS: To identify levels of Australian rural general practitioners' apprehension
      about violence, factors effecting apprehension and the effect of apprehension on
      service provision. METHOD: Six focus groups were held with rural GPs from Western
      Australia, New South Wales and Victoria. A questionnaire was developed on the
      basis of the focus group data and all GPs in these three areas were surveyed.
      RESULTS: The results indicated GPs were more apprehensive about providing after
      hours care than during business hours. Significant gender differences were found
      with women being more often apprehensive than men and more likely to withdraw
      after hours services. CONCLUSION: This study shows that that levels of
      apprehension about violence affect GPs' willingness to provide after hours
      services. Future provision of general practice after hours services and home
      visits in rural areas requires the availability of a safe working environment to
      reduce GPs' apprehension about workplace violence.

PMID- 14641222
TI  - Evidence-based practice in rural and remote clinical practice: where is the
      evidence?
AB  - OBJECTIVE: To critically review the evidence regarding barriers to implementing
      research findings in rural and remote settings, and the ways those barriers have
      been addressed. DESIGN: A systematic review that included searching several
      electronic databases, Internet sites and reference lists of relevant articles,
      assessment of methodological quality of the studies, and data extraction and
      analysis where possible. Eligibility for the review was not limited by study
      design. SETTINGS/PARTICIPANTS: Studies that reported on: (1) barriers to the
      implementation of evidence by health professionals in rural and remote areas, or
      (2) interventions for implementing evidence-based practice or an element of
      evidence-based practice in rural and remote areas. RESULTS: There were no
      experimental data available on the implementation of research findings in rural
      and remote clinical settings. The small amounts of empirical research undertaken
      (surveys) showed that some of the problems experienced by general practitioners
      were exacerbated by rural and remote location, particularly with relation to
      isolation, lack of time and locum cover, and poor information technology
      infrastructure. CONCLUSION: There is a paucity of empirical literature on
      implementing evidence-based practice in rural and remote settings. This is in
      contrast to the large amount of literature available on implementing evidence in
      other clinical settings. A clear finding from the literature was that getting
      evidence into practice needs to be context-specific and yet very little research
      has been conducted into the rural and remote context. Research is needed into how
      evidence can be implemented in contextually specific ways in rural and remote
      areas.

PMID- 14641223
TI  - Community perception of rural hospital conversion/closure: re-conceptualising as
      a critical incident.
AB  - BACKGROUND: In this article, a consideration of the role and meaning of the rural
      hospital is contextualised within the health reform environment in Saskatchewan
      (Canada). Individual and community perceptions of the impact of the
      conversion/closure of a rural hospital are often unheard and more often unheeded.
      Some researchers suggest hospital conversion/closure is a devastating event in
      the life of rural communities, yielding long-lasting medical, economic and
      psychological consequences. METHOD: This article examines the concept of critical
      incidents with the intent of proposing a working definition of the concept.
      Lazarus and Folkman's (1984) construct of appraisal provides the framework for
      discussion and re-conceptualisation of critical incidents. RESULTS AND
      CONCLUSIONS: The recommendation is to consider the adoption of an alternate
      definition of critical incident shifting away from professional or external
      delineation of an event's meaning. The proposed definition states that a critical
      incident is any external event that alters an individual's or community's life
      from the perspective of that individual or community. Finally, the
      conversion/closure of a rural hospital is considered within this re
      conceptualised 'critical incident' definition.

PMID- 14641224
TI  - Approaching primary health care through 'Country Week': the impact of a rural
      placement program on the student learning experience.

PMID- 14641226
TI  - Rural and remote medicine: comes of age.

PMID- 14641227
TI  - Cancer inpatients morphine usage: a new England area survey.
AB  - This is a one year study of the use of morphine in cancer patients in 10
      inpatient facilities in the New England Area Health Service in the north-west of
      New South Wales. The study explored 170 admissions relating to 122 patients, most
      of whom were cared for by their general practitioners. The use of morphine in
      these cancer patients was compared with the recommendations made by the expert
      working group of the European Association of Palliative Care.1 Those items which
      matched the recommendations included the initial doses for new users of morphine
      and the subcutaneous route being the preferred parenteral route. The data in this
      study differed from the recommendations in that only half of the patients
      received the immediate release morphine when first given oral morphine, only 43%
      had orders for immediate release oral morphine for breakthrough pain (with a
      variable frequency) and a significant number of orders for parenteral and
      immediate release oral morphine for breakthrough pain were outside the
      recommended doses (100% and 86.2%, respectively). Written orders for immediate
      release oral and parenteral morphine involved a dose range in significant numbers
      while only 30% of patients had orders for parenteral morphine for breakthrough
      pain. There was a low use of fixed interval variable dose (FIVD) morphine charts
      despite these being available in most facilities.

PMID- 14641228
TI  - Impact of lead transport on children's blood and environmental lead levels.
AB  - INTRODUCTION: A lead monitoring project was established in 1996 to monitor the
      environmental and health effects of lead being transported through a remote town
      in tarpaulin-covered trucks. METHODS: Dust samples from sites on the transport
      route were collected at 3-6 monthly intervals between 1996 and 1999. Annual blood
      lead testing clinics, offering voluntary testing to children, were conducted from
      1997 to 1999. RESULTS: Of the 55 dust samples analysed, only nine contained
      particles of lead concentrate and these were present at very low levels. During
      the project 167 children were tested. The geometic mean of blood lead levels in
      1997, 1998 and 1999 were 4.5 micro g/dL, 5.0 micro g/dL and 5.1 micro g/dL,
      respectively (all within the normal range). Residence on the transport route was
      not associated with higher lead levels (P > 0.05). CONCLUSIONS: Lead transport
      was not associated with any detectable environmental contamination or increase in
      children's blood lead levels.

PMID- 14641229
TI  - First year of practice visits for the Rural Depression Anxiety Research and
      Treatment General Practice program.
AB  - OBJECTIVE: To describe the first 12 months activities of a key component of a
      General Practice Psychiatry program - the GP practice visit. DESIGN:
      Questionnaire to evaluate effects on participating general practitioners
      practice. SETTING: Rural group general practices. SUBJECTS: Thirty-two general
      practitioners in the Loddon Campaspe Southern Mallee region in Victoria.
      INTERVENTIONS: Practice visits involved a combination of each of three key
      activities: primary consultation, secondary consultation and/or case discussion
      and formal teaching. RESULTS: General practitioners reported a variety of changes
      in their practice as a result of the visits. CONCLUSION: Practice visits appear
      to be a useful means of influencing GP's practice. Further work is required to
      determine whether such changes are accompanied by demonstrable benefits in
      patient outcome. WHAT IS ALREADY KNOWN: Several models to assist GPs effectively
      manage mental health problems have been described. These models require regular
      contact and so have had limited utility in rural settings. WHAT THIS STUDY ADDS:
      This study suggests that infrequent contact or input, based on well established
      models, can alter GP's clinical behaviour.

PMID- 14641230
TI  - Balancing hospital and community treatment: effectiveness of an extended-hours
      community mental health team in a semi-rural region of australia.
AB  - OBJECTIVE: To examine the effectiveness of the introduction of a community mental
      health team on consumer psychosocial outcomes. DESIGN: Longitudinal panel design.
      SETTING: District general hospital in a semi-rural region of Australia. NUMBERS:
      Two matched groups (n = 37 in each group) MAIN OUTCOME MEASURE: These included:
      Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), Rosenberg
      Self-Esteem, Life Skills Profile as well as self-report. RESULTS: The study found
      that the introduction of the new service resulted in few significant differences
      in consumer outcomes. CONCLUSIONS: The paper argues that because the state was
      the only specialist mental health service provider and it was unable to offer
      assertive community treatment, hospital care remained central. Evidence that a
      substantial proportion of consumers and carers preferred hospital to community
      care is placed against this background. The paper argues that in regions like
      these, where community-based services are likely to remain underdeveloped, it may
      be best to maintain quality hospital services and to target community services
      more precisely on what is achievable rather than developing community services at
      the expense of hospital care. WHAT IS ALREADY KNOWN: Studies on the efficacy of
      assertive community treatment suggest that it can lead to improved consumer
      outcomes. However, these studies are usually in urban settings and involve
      experimental teams. In many rural and regional areas community treatment teams
      offer standard rather than assertive community care. It is therefore important to
      investigate the effectiveness of community treatment teams in rural and regional
      Australia. WHAT THIS STUDY ADDS: This study suggests that in rural and regional
      areas characterised by limited resources, it is too much to expect community
      treatment teams to have a measurable impact on consumer outcomes. In these
      settings hospital care remains at the heart of the service. This means that
      regions such as these need to focus their community services on what is
      achievable given the level of resources and social ecology. For example, they may
      need to consider offering either crisis intervention or rehabilitation services
      and to rely on innovations, such as telehealth or strategic alliances with other
      service providers to fill the gap.

PMID- 14641231
TI  - Identifying musculoskeletal conditions among rural indigenous peoples.
AB  - OBJECTIVE: To critically review the methodological properties of previous
      musculoskeletal studies among Indigenous populations. In particular, non
      rheumatic, musculoskeletal conditions of mechanical origin are examined as these
      appear to be commonly related to syndromes of pain and disability. DESIGN:
      Systematic review. SETTING: Rural, Indigenous communities throughout the world.
      SUBJECTS: Indigenous peoples aged 16 and over living in rural communities. MAIN
      OUTCOME MEASURE: Minimum requirements for methodologically sound musculoskeletal
      health research according to previously published criteria. RESULTS: Due to
      methodological limitations in the 14 studies reviewed, only five methodologically
      acceptable studies were found. CONCLUSION: Given the paucity of methodologically
      sound musculoskeletal studies among Indigenous populations, the true prevalence
      of musculoskeletal conditions in these communities remains largely unknown.

PMID- 14641232
TI  - Getting the balance right? GPs who chose to stay in rural practice.
AB  - BACKGROUND: Despite major challenges to the retention of rural GPs in Australia,
      little is known about why some rural GPs stay long-term within their communities.
      METHOD: A group of rural GPs interviewed as part of another study about 10 years
      ago were re-interviewed to explore their attitudes to their reasons for staying.
      RESULTS: Eighteen of the original group of 23 could be contacted and 13 were
      interviewed. Factors that appeared to promote staying in rural practice were:
      strong attachment to the community; and practice arrangements that allow for
      adequate time off-call and for holidays. However, several GPs were stressed and
      some had considered leaving. The stressors were similar to those identified in
      earlier research, including overwork and having to send children to boarding
      school. CONCLUSION: Personal and professional support arrangements within the
      community appear to be associated with decisions by rural GPs to remain in
      practice for substantial periods of time. Retention strategies should focus on
      facilitation of local integration. WHAT IS ALREADY KNOWN: Some doctors stay for
      prolonged periods of time in rural practice, although most leave after a few
      months or years. The reasons why rural doctors stay have until now not been
      explored. WHAT THIS STUDY ADDS: Rural doctors who stay for prolonged periods of
      time, defined in this study as 10 or more years, have established personal and
      professional support networks that have provided protection from the more
      negative aspects of rural professional life.

PMID- 14641233
TI  - Health career promotion in the New England area of New South Wales: a program to
      support high school career advisers.
AB  - OBJECTIVE: To facilitate the area's high school careers advisers' ability to
      effectively promote health careers to students. DESIGN: Three cross sectional
      evaluation surveys at the end of each one-day workshop. SETTING: Conference rooms
      in three regional centres (Armidale, Moree and Tamworth, New South Wales).
      SUBJECTS: Twenty-two high school careers advisers. INTERVENTION: One-day
      workshop. MAIN OUTCOME MEASURES: High school careers advisers' self-rated
      assessment in terms of the effective delivery of appropriate information and
      opportunities to network. RESULTS: Participants agreed that the workshop conveyed
      relevant information (3.8), were of high standard (3.5) and enabled them to
      identify students wanting to pursue health careers (2.9). Networking between
      health professionals and career advisers was rated as the most beneficial aspect
      by a majority of participants (60%). The scenario was rated as a useful tool to
      educate advisers about health careers (3.8). CONCLUSION: Collaborative workshops
      between advisers and health professionals are useful in facilitating networks to
      promote health careers in high schools in rural areas. The use of a farm injury
      scenario as a learning tool was effective in educating advisers about health
      careers. WHAT IS ALREADY KNOWN: Previous research carried out in the USA6 and
      Australia demonstrated that high school careers advisers needed to target high
      school students earlier in their studies before senior subjects were decided and
      that about a quarter of careers advisers indicated poor knowledge about health
      careers.10 WHAT THIS STUDY ADDS: Provision of practical support to high school
      careers advisers, such as distributing a mentorship directory and up-to-date
      health career kits as well as facilitating networking with health professionals
      constitute effective means to promote health careers to high school students.

PMID- 14641234
TI  - Barriers to managing mental health in Western Australia.
AB  - OBJECTIVE: To explore the views of community-care and mental health workers on
      barriers to the management of mental health problems in rural Western Australia,
      and how these could be addressed. DESIGN: Qualitative content analysis of semi
      structured interviews. SETTING: Community and mental health services in
      Esperance. SUBJECTS: One hundred per cent of relevant mental health workers, 86%
      of community health professionals and representatives from a wide range of
      community organisations were interviewed (n = 38). MAIN OUTCOME MEASURES: The
      views of community-care and mental health workers on barriers to the management
      of mental health, and how these could be addressed. RESULTS: Barriers included
      confusion about the role of mental health services, limited after-hours access
      and help for those in situational crisis, communication problems between
      services, differences in working practices and difficulties in dealing with the
      stigma of mental illness in rural communities. Suggested solutions were an
      expansion of counselling services and multi-agency shared care with clinical
      streams for adults, those aged > 65 and children. CONCLUSION: This study revealed
      a number of barriers that are being addressed through a memorandum of
      understanding between services. WHAT IS ALREADY KNOWN: Initiatives to foster
      collaboration between rural mental health services and general practitioners have
      not included other providers of primary care. We wished to explore the views of
      community-care and mental health workers on barriers to the management of mental
      health problems in rural Western Australia and how these could be addressed. WHAT
      THIS STUDY ADDS: We identified a number of barriers to collaboration between
      mental health and community-based services, including poor communication,
      difficulties with referral and cultural differences between services. Of all
      these themes, the most significant was the lack of communication at individual,
      case management and organisational levels.

PMID- 14641235
TI  - ACRRM: practice analysis.

PMID- 14641236
TI  - A metric linkage disequilibrium map of a human chromosome.
AB  - We used LDMAP (Maniatis et al. 2002) to analyse SNP data spanning chromosome 22
      (Dawson et al. 2002), to obtain a whole-chromosome metric LD map. The LD map,
      with map distances analogous to the centiMorgan scale of linkage maps, identifies
      regions of high LD as plateaus ('blocks') and characterises steps which define
      the relationship between these regions. From this map we estimate that block
      regions comprise between 32% and 55% of the euchromatic portion of chromosome 22
      and that increasing marker density within steps may increase block coverage.
      Steps are regions of low LD which correspond to areas of variable recombination
      intensity. The intensity of recombination is related to the height of the step
      and thus intense recombination hot-spots can be distinguished from more randomly
      distributed historical events. The LD maps are more closely related to the high
      resolution linkage map (Kong et al. 2002) than average measures of rho with
      recombination accounting for between 34% and 52% of the variance in patterns of
      LD (r=0.58 - 0.71, p=0.0001). Step regions are closely correlated with a range of
      sequence motifs including GT/CA repeats. The LD map identifies holes in which
      greater marker density is required and defines the optimal SNP spacing for
      positional cloning, which suggests that some multiple of around 50,000 SNPs will
      be required to efficiently screen Caucasian genomes. Further analyses which
      investigate selection of informative SNPs and the effect of SNP allele frequency
      and marker density will refine this estimate.

PMID- 14641237
TI  - A 34 bp deletion within TSC2 is a rare polymorphism, not a pathogenic mutation.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome due to
      mutations in either TSC1 or TSC2. Previous reports have identified a mutation
      consisting of a 34 bp deletion affecting portions of exon 38 and the adjacent
      intron 38 of TSC2. We found this genetic variation in 4 of 800 TSC patients
      screened for mutations in TSC1 and TSC2. In every case, the variant was present
      in one unaffected parent of the sporadically affected TSC child. By RT-PCR
      analysis of RNA samples from two additional families with this genetic variant,
      we demonstrate that the allele with the deletion generates about 50% normal RNA
      transcript, and 50% RNA transcript including intron 38. In addition, there is no
      correlation between the extent of splicing and clinical status of family members.
      We also excluded the possibility of mosaicism in the parents with this variant.
      We conclude that this deletion is a rare polymorphism that does not cause TSC,
      but may be a modifier of the TSC phenotype.

PMID- 14641238
TI  - SELPLG gene polymorphisms in relation to plasma SELPLG levels and coronary artery
      disease.
AB  - P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand)
      constitute a receptor/ligand complex that is likely to be involved in the
      development of atherosclerosis and its complications. While the genetic
      variability of P-selectin has already been investigated in depth, that of the
      SELPLG gene has not yet been extensively explored. The coding and regulatory
      sequences of the SELPLG were screened and nine polymorphisms were identified. The
      identified polymorphisms were genotyped in the AtheroGene study, a case-control
      study of coronary artery disease (CAD). Haplotype analysis revealed that two
      polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma
      SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD
      risk.

PMID- 14641239
TI  - Identification of Native American founder mtDNAs through the analysis of complete
      mtDNA sequences: some caveats.
AB  - In this study, a detailed analysis of both previously published and new data was
      performed to determine whether complete, or almost complete, mtDNA sequences can
      resolve the long-debated issue of which Asian mtDNAs were founder sequences for
      the Native American mtDNA pool. Unfortunately, we now know that coding region
      data and their analysis are not without problems. To obtain and report reasonably
      correct sequences does not seem to be a trivial task, and to discriminate between
      Asian and Native American mtDNA ancestries may be more complex than previously
      believed. It is essential to take into account the effects of mutational hot
      spots in both the control and coding regions, so that the number of apparent
      Native American mtDNA founder sequences is not erroneously inflated. As we report
      here, a careful analysis of all available data indicates that there is very
      little evidence that more than five founder mtDNA sequences entered Beringia
      before the Last Glacial Maximum and left their traces in the current Native
      American mtDNA pool.

PMID- 14641240
TI  - An analysis of consanguinity and social structure within the UK Asian population
      using microsatellite data.
AB  - We analysed microsatellite genotypes sampled from the Pakistani and Indian
      communities in Nottingham, UK, to investigate the genetic consequences of
      substructuring mediated by traditional marriage customs. The application of a
      recently developed likelihood approach identified significant levels of
      population substructure within the Pakistani community as a whole, as well as
      within the finer divisions of castes and biradheri. In addition, high levels of
      cryptic or unacknowledged consanguinity were detected within subgroups of this
      community, including biradheri. The Indian sample showed no significant evidence
      of either substructure or consanguinity. We demonstrate that estimates of disease
      gene frequencies can be inaccurate unless they are made jointly with estimates of
      population substructure and consanguinity ((theta congruent to FST) and C). The
      magnitude of these estimates also highlights the importance of accounting for the
      finer scale of social structuring when making decisions regarding the risk of
      recessive disorders in offspring.

PMID- 14641241
TI  - Maternal effect: an additional mechanism maintaining balanced polymorphisms of
      haemoglobinopathies?
AB  - The malarial hypothesis presupposes that carriers of sickle cell trait and beta
      thalassaemia are born in accordance with Mendelian inheritance and later favoured
      by an environmental factor. However, an eventual distortion favouring the
      transmission of the mutant allele is also a plausible hypothesis. The Mendelian
      proportion was tested in the progeny of 201 sickle cell trait (AS) and 138 beta
      thalassaemia (AT) probands married to individuals with normal haemoglobin (AA).
      An excess of births of heterozygotes in the offspring of the 107 AS mothers (144
      AS:89 AA, chi2=12.98; p<0.001) and 95 AT mothers (117 AT:66 AA, chi2=14.21;
      p<0.001) married to homozygous normal fathers was observed, but not for births to
      the reverse parental combinations (103 AS: 101 AA, chi2=0.019; p=0.89 and 57
      AT:42 AA, chi2=2.27; p=0.13). Such data reveal a statistically significant
      maternal effect favouring the transmission of haemoglobin S and beta-thalassaemia
      alleles. Obviously, prezygotic and postzygotic mechanisms of distortion cannot be
      ignored and need further investigation. However, the selective embryonic survival
      of AS and AT conceptuses of heterozygotic mothers, with an excess of unrecognized
      very early embryonic deaths among the AA conceptuses is a very attractive
      hypothesis that should also be taken into consideration.

PMID- 14641242
TI  - SNP subset selection for genetic association studies.
AB  - Association studies for disease susceptibility genes rely on the high density of
      SNPs within candidate genes. However, the linkage disequilibrium between SNPs
      imply that not all SNPs identified in the candidate region need be genotyped.
      Here we develop several approaches to SNP subset selection, which can
      substantially reduce the number of SNPs to be genotyped in an association study.
      We apply clustering algorithms to pairwise linkage disequilibrium measures, with
      SNP subsets determined for different cut-off values of Delta using nearest and
      furthest neighbour clusters. Alternatively, SNP subsets may be determined by the
      proportion of haplotypes they identify. We also show how power calculations,
      based on the average power to identify a SNP as the disease susceptibility
      mutation using haplotype-based or logistic regression based statistical analyses,
      can be used to choose SNP subsets. All these methods provide a ranking method for
      subsets of a specific size, but do not provide criteria for overall choice of SNP
      subset size. We develop such criteria by incorporating power calculations into a
      decision analysis, where the choice of SNP subset size depends on the genotyping
      costs and the perceived benefits of identifying association. These methods are
      illustrated using eleven SNPs in the MMP2 gene.

PMID- 14641243
TI  - Power of linkage disequilibrium mapping to detect a quantitative trait locus
      (QTL) in selected samples of unrelated individuals.
AB  - We considered a strategy to map quantitative trait loci (QTLs) using linkage
      disequilibrium (LD) when the QTL and marker locus were multiallelic. The strategy
      involved phenotyping a large number of unrelated individuals and genotyping only
      selected individuals from the two tails of the trait distribution. Power to
      detect trait-marker association was assessed as a function of the number of QTL
      and marker alleles. Two patterns of LD were used to study their influence on
      power. When the frequency of the QTL allele with the largest effect and that of
      the marker allele linked in coupling were equal, power was maximum. In this case,
      increasing the number of QTL alleles reduced the power. The maximum difference in
      power between the two LD patterns studied was approximately 30%. For low QTL
      heritabilities (h2QTL<0.1) and single trait studies we recommend selecting around
      5% of the upper and lower tails of the trait distribution.

PMID- 14641244
TI  - Quantifying the intragenic distribution of human disease mutations.
AB  - A wide variety of functional domains exist within human genes. Since different
      domains vary in their roles regarding overall gene function, the ability for a
      mutation in a gene region to produce disease varies among domains. We tested two
      hypotheses regarding distributions of mutations among functional domains by using
      (1) sets of single nucleotide disease mutations for six genes (CFTR, TSC2, G6PD,
      PAX6, RS1, and PAH) and (2) sets of polymorphic replacement and silent mutations
      found in two genes (CFTR and TSC2). First, we tested the null hypothesis that
      sets of mutations are uniformly distributed among functional domains within
      genes. Second, we tested the null hypothesis that disease mutations are
      distributed among gene regions according to expectations derived from the
      distribution of evolutionary conserved and variable amino acid sites throughout
      each gene. In contrast to the mainly uniform distribution of sets of silent and
      polymorphic mutations, sets of disease mutations generally rejected the null
      hypotheses of both uniform and evolutionary-influenced distributions. Although
      the disease mutation data showed a better agreement with the evolutionary-derived
      expectations, disease mutations were found to be statistically overabundant in
      conserved domains, and under-represented in variable regions, even after
      accounting for amino acid site variability of domains over long-term evolutionary
      history. This finding suggests that there is a non-additive influence of amino
      acid site conservation on the observed intragenic distribution of disease
      mutations, and underscores the importance of understanding the patterns of
      neutral amino acid substitutions permitted in a gene over long-term evolutionary
      history.

PMID- 14641245
TI  - Admixture mapping using interval transmission/disequilibrium tests.
AB  - Family-based studies of genetic association and linkage play a key role in
      mapping susceptibility genes of complex human diseases. Recent admixture between
      genetically differentiated populations can result in high levels of linkage
      disequilibrium even at far apart loci. This has been capitalized upon to reduce
      the burden of genotyping in a genomewide association scan. Here the authors
      describe an alternative approach for admixture mapping. The genome is divided
      into several non-overlapping intervals and the information of the markers in the
      same interval is integrated--the 'interval transmission/disequilibrium test'
      (ITDT). This method requires information in the form of the marker allele
      frequencies in the founding populations. However, computer simulations show that
      the performances of ITDT are hardly affected by imprecise allele-frequency
      information. Simulations also show that an interval-by-interval scan using ITDT
      perform much better than a conventional marker-by-marker scan using TDT, even
      under conditions where the admixture process occurred over many generations and
      the individuals in the admixed populations show considerable variation in
      admixture proportion. Hence the ITDT is a promising new genomewide scan method.

PMID- 14641246
TI  - Tests for candidate-gene association using case-parents design.
AB  - In the case-parents design for testing candidate-gene association, the
      conditional likelihood method based on genotype relative risks has been developed
      recently. A specific relation of the genotype relative risks is referred to as a
      genetic model. The efficient score tests have been used when the genetic model is
      correctly specified under the alternative hypothesis. In practice, however, it is
      usually not able to specify the genetic model correctly. In the latter situation,
      tests such as the likelihood ratio test (LRT) and the MAX3 (the maximum of the
      three score statistics for dominant, additive, and recessive models) have been
      used. In this paper, we consider the restricted likelihood ratio test (RLRT). For
      a specific genetic model, simulation results demonstrate that RLRT is
      asymptotically equivalent to the score test, and both are more powerful than the
      LRT. When the genetic model cannot be correctly specified, the simulation results
      show that RLRT is most robust and powerful in the situations we studied. MAX3 is
      the next most robust and powerful test. The TDT is the easiest statistic to
      compute, compared to MAX3 and RLRT. When the recessive model can be eliminated,
      it is also as robust and powerful as RLRT for other genetic models.

PMID- 14641247
TI  - Logistic regression models for polymorphic and antagonistic pleiotropic gene
      action on human aging and longevity.
AB  - In this paper, we apply logistic regression models to measure genetic association
      with human survival for highly polymorphic and pleiotropic genes. By modelling
      genotype frequency as a function of age, we introduce a logistic regression model
      with polytomous responses to handle the polymorphic situation. Genotype and
      allele-based parameterization can be used to investigate the modes of gene action
      and to reduce the number of parameters, so that the power is increased while the
      amount of multiple testing minimized. A binomial logistic regression model with
      fractional polynomials is used to capture the age-dependent or antagonistic
      pleiotropic effects. The models are applied to HFE genotype data to assess the
      effects on human longevity by different alleles and to detect if an age-dependent
      effect exists. Application has shown that these methods can serve as useful tools
      in searching for important gene variations that contribute to human aging and
      longevity.

PMID- 14641248
TI  - Accelerated gene counting for haplotype frequency estimation.
AB  - Current implementations of the EM algorithm for estimating haplotype frequencies
      from genotypes on proximal loci require computational resources that grow as
      nh2k, where n is the number of individuals genotyped and h is the number of
      haplotypes possible on k loci. For diallelic loci hk=2k. We present an approach
      whose computational requirement grows as n2t where t is the largest number of
      loci at which an individual in the sample is heterozygous. The method is
      illustrated by haplotype frequency estimation from a sample of 45 individuals
      genotyped at 26 single nucleotide polymorphisms in the PIK3R1 gene.

PMID- 14641249
TI  - A note on including phenotypic information from monozygotic twins in variance
      components QTL linkage analysis.
AB  - Williams & Blangero (1999) derived closed form expressions for the power of a
      univariate variance components test of linkage for a variety of pedigree
      structures. We have extended their results by investigating the effect of
      including monozygotic twins in the design on the power to detect linkage.
      Specifically, we determined the power associated with a pedigree of size three,
      where individuals one and two were monozygotic twins and individual three was a
      full sibling to the twins. The power of this sampling unit was uniformly greater
      than the power obtained from a sib-pair under the same genetic model. The reason
      for this was that addition of a second monozygotic twin provided another estimate
      of the sibling correlation for the particular IBD class. In addition, when the
      total heritability of the trait was <50%, the number of individuals that needed
      to be phenotyped was less than that with sib-pairs alone. However, a pedigree
      consisting of a monozygotic pair and sibling was never as informative as a sib
      trio, presumably because the sib-trio provided information about allele sharing
      between three individuals, whereas the monozygotic twins and sibling unit only
      provided one such relationship. We conclude that including a monozygotic twin in
      the analysis is an economical strategy, since only one twin needs to be
      genotyped.

PMID- 14641250
TI  - Testing the genetic relation between two individuals using a panel of frequency
      unknown single nucleotide polymorphisms.
AB  - The author proposes a method to test the genetic relation between two individuals
      using a panel of SNPs. The method does not require information about the allele
      frequencies, and as such it can be used to test any pair of individuals from any
      population(s).

PMID- 14641253
TI  - Glaucoma surgery: lest we forget.

PMID- 14641254
TI  - Nordic research in ophthalmology.
AB  - PURPOSE: To provide an overview of some of the current activities in eye research
      in the Nordic countries. METHODS: The presentations at the biannual Nordic
      Congress of Ophthalmology, held in Tampere, Finland in 2002, were reviewed and
      the contributions found most noteworthy are included in this article along with a
      limited discussion of each research field. However, space requirements prevented
      the inclusion of many interesting scientific contributions. RESULTS: Important
      contributions in various subfields of eye research and ophthalmology are
      reviewed. These include cornea, cataract, paediatric ophthalmology, glaucoma,
      diabetic eye disease, age-related macular degeneration, physiology and
      pharmacology and oncology. CONCLUSIONS: Eye research is very active in the Nordic
      countries and significant contributions are being made to ophthalmology in
      several fields on a world scale. We hope to continue to review Nordic
      contributions to eye research after each Nordic Congress of Ophthalmology and
      plan to make the reviews more systematic and comprehensive in the future.

PMID- 14641255
TI  - Deep sclerectomy in patients with capsular glaucoma.
AB  - PURPOSE: To compare the results of deep sclerectomy in capsular glaucoma (CG)
      with those in primary open-angle glaucoma (POAG). METHODS: This consecutive,
      prospective study comprised 24 CG patients (28 eyes) and 25 POAG patients (29
      eyes) who underwent deep sclerectomy. Two different implants were used: either an
      absorbable collagen implant (Aqua-Flow) or a non-absorbable hydrophilic acrylic
      implant (T-Flux). The number of glaucoma medications, intraocular pressure (IOP)
      and complications were compared postoperatively. The definition of complete
      success was IOP below 19 mmHg without therapy. RESULTS: After a mean follow-up of
      19.9 +/- 10.9 months (range 6-36 months) in the CG group and 16.2 +/- 10.0 months
      (range 6-36 months) in the POAG group, complete success was seen in 60.7% and in
      37.9% of eyes, respectively (p=0.085). After adjustments for disparities in
      baseline characteristics, survival analysis demonstrated that success rates were
      better over time in CG eyes than in POAG eyes (p=0.038). At all time-points,
      except at 24 months, the IOP was lower in the CG group than in the POAG group.
      This difference was statistically significant at 1 week (p=0.050) and 3 months
      (p=0.006). At 18 months, the mean decrease in number of medications was 77.3% in
      the CG group and 65.9% in the POAG group (not statistically significant).
      Levelled hyphema occurred more frequently in CG eyes (35.7%) than in POAG eyes
      (13.8%). CONCLUSION: Capsular glaucoma patients had significantly higher success
      rates over time than POAG patients following deep sclerectomy with implant.

PMID- 14641256
TI  - Complications of Neodymium:YAG laser goniopuncture after deep sclerectomy.
AB  - PURPOSE: To study the complications of Neodymium:YAG (Nd:YAG) goniopuncture after
      deep sclerectomy with collagen implant (DSCI). METHODS: All patients who
      underwent a Nd:YAG goniopuncture after a successful DSCI for primary open-angle
      glaucoma were included in a non-randomized clinical study. RESULTS: Nd:YAG
      goniopuncture was performed in 31 patients. The mean time from surgery to
      goniopuncture was 3.2 +/- 3.2 months. The mean intraocular pressure (IOP) before
      goniopuncture was 32.0 +/- 10.8 mmHg (SD); the mean IOP 1-2 hours after
      goniopuncture was 16.5 +/- 6.3 mmHg. After a mean follow-up of 5.4 +/- 2.8
      months, the mean IOP was 17.8 +/- 11.6 mmHg. Three patients had a spontaneous
      iris prolapse after Nd:YAG goniopuncture and consequently high IOP. No signs of
      severe hypotension were observed. CONCLUSION: There are potentially serious
      complications relating to Nd:YAG goniopuncture after deep sclerectomy. However,
      further studies are needed to determine the safest time and level of IOP at which
      to perform Nd:YAG goniopuncture.

PMID- 14641257
TI  - Needling revision of failed filtering blebs after trabeculectomy: a retrospective
      study.
AB  - PURPOSE: To determine the efficacy and safety of needling revision of failed
      filtering blebs. METHODS: We reviewed retrospectively 26 eyes that had undergone
      needling revision for a failed trabeculectomy. The needling revisions were
      performed either with adjunctive use of Mitomycin C, 5-Fluorouracil or without
      antimetabolites. The procedure was usually performed as a clinic procedure, using
      a 27-gauge needle. RESULTS: The mean follow-up time was 14.5 +/- 11.3 months
      (range 6.0-48.0 months). Intraocular pressure (IOP) decreased from 28.8 +/- 6.8
      mmHg (range 19.0-40.0 mmHg) to 15.3 +/- 5.2 mmHg (range 7.0-35.0 mmHg). Twelve
      eyes (46.2%) achieved success, defined as IOP < or = 18 mmHg without medication;
      11 eyes (42.3%) achieved qualified success, defined as IOP < or = 18 mmHg with
      antiglaucomatous medication, and three of 26 eyes (11.5%) were classified as
      failures. The success rate after the initial needling was 64% at 6 months and the
      same after 1 year and 2 years. The success rate after one or more needlings was
      96% at 6 months and 77% at 1 year and 2 years. Complications developed in six of
      the 26 eyes (23.1%). These involved transient corneal epithelial defects in three
      eyes (11.5%), temporary conjunctival wound leak in two eyes (7.7%), and
      development of bullous keratopathy in one high risk eye (3.8%). CONCLUSION: Our
      results are comparable to the results of other studies. Needling revision appears
      to be a useful tool in the management of glaucoma.

PMID- 14641258
TI  - The effects of chronic smoking on the ocular surface and tear characteristics: a
      clinical, histological and biochemical study.
AB  - PURPOSE: To investigate the effects of chronic smoking on the ocular surface and
      tear characteristics. METHODS: The Schirmer I-test, tear film break-up time, rose
      Bengal staining scores, impression cytology, tear lysozyme concentration, eye
      irritation symptoms, and eye irritation indices were determined for 44 eyes in 44
      healthy, chronic smokers who had smoked six or more cigarettes per day for the
      previous year. Thirty-seven eyes in 37 healthy, non-smokers were assessed in the
      same masked manner for comparison. Cytological specimens were obtained from the
      temporal interpalpebral bulbar conjunctiva by 'impression' technique. Goblet
      cells were counted in the specimens obtained and squamous metaplasia was graded
      following epithelial cell morphology assessment. RESULTS: In chronic smokers, we
      found decreased tear film break-up time (p=0.022) and tear lysozyme concentration
      (p=0.013), and increased Schirmer I-test values (p=0.047), squamous metaplasia
      scores (p=0.016), eye irritation scores (p<0.001) and eye irritation indices
      (p=0.013), as compared with the control group. There were no statistically
      significant differences in goblet cell counts (p=0.710) or rose Bengal staining
      scores (p=0.827). CONCLUSION: These findings suggest that chronic smoking has a
      negative effect on the ocular surface and affects some tear characteristics. The
      chronic ocular irritative effects of cigarette smoking may lead to defects in
      ocular surface defence.

PMID- 14641259
TI  - Myopia and natural lighting extremes: risk factors in Finnish army conscripts.
AB  - PURPOSE: To establish whether features of environmental lighting in far northern
      latitudes might be associated with prevalence of myopia. METHODS: Using both
      questionnaires and military medical examinations, this cross-sectional survey of
      Finnish conscripts assessed both light exposure and conventional risk factors for
      myopia. RESULTS: While myopia was not associated with the month of birth, there
      was a trend towards a higher prevalence of myopia among conscripts living above
      the Arctic Circle, consistent with the hypothesis that ambient lighting might
      influence refractive development. Other novel associations with myopia were
      decreased sunglasses use and brown iris colour. As indicated by other reports,
      myopia was found to be associated with family history, education and nearwork.
      CONCLUSION: Although constraints inherent in surveying this military population
      may have limited our ability to detect associations, the positive findings
      suggest that studying northern populations may prove useful in clarifying any
      potential role of the light/dark cycle in refractive development.

PMID- 14641260
TI  - Topical versus peribulbar anaesthesia for cataract surgery.
AB  - BACKGROUND: To assess and compare the efficacy and safety of topical versus
      peribulbar anaesthesia in patients undergoing routine cataract surgery. METHODS:
      The unicentre, prospective, randomized, clinical interventional trial included
      140 consecutive patients undergoing routine cataract surgery performed by one of
      two surgeons. The patients were randomly distributed to either peribulbar
      anaesthesia or topical anaesthesia. To assess intraoperative pain, each patient
      was asked immediately after surgery to quantitate his/her pain using a 10-point
      pain rating scale. RESULTS: The study groups did not differ significantly in pain
      score (p=0.54), duration of surgery (p=0.52), anaesthesia-related intraoperative
      difficulties (p=0.17), postoperative visual acuity (p=0.94), overall
      intraoperative surgical complication rate, blood pressure rise (p=0.16) or blood
      oxygen saturation (p=0.74) CONCLUSIONS: Patient comfort and surgery-related
      complications did not differ between topical anaesthesia and peribulbar
      anaesthesia. As there are no significant differences between the two techniques
      in terms of subjective pain experienced by patients, intraoperative complications
      and postoperative visual outcome, and in view of the minimally invasive character
      of topical anaesthesia compared to peribulbar anaesthesia, the present study
      suggests the use of topical anaesthesia for routine cataract surgery.

PMID- 14641261
TI  - Computer-assisted training system for pars plana vitrectomy.
AB  - PURPOSE: To evaluate whether microsurgical steps in vitreoretinal surgery can be
      taught by a computer-assisted training system. METHODS: This prospective,
      randomized experimental study included 14 ophthalmic residents and medical
      students who were completely inexperienced in microsurgery. They were randomized
      into two groups. The study group underwent training programmes in a computer
      assisted training system for simulation of pars plana vitrectomy. The control
      group did not participate in any in vitro training. In the second phase of the
      study, participants of both groups performed a pars plana vitrectomy in three pig
      eyes, which included picking a metallic foreign body from the retinal surface.
      RESULTS: The amount of retinal detachment and the number of retinal defects at
      the end of the vitrectomies were smaller, the time needed to remove the foreign
      body was shorter, the number of retinal lesions associated with the foreign body
      removal was lower, and the mark given was better in the trained study group than
      in the untrained group. The relatively small number of study participants did not
      allow the differences between the study and control groups to reach the 5% level
      of error probability. CONCLUSIONS: In an animal model, training by a computer
      based medical work station for simulation of pars plana vitrectomy showed better
      outcome measures for trained study participants compared with untrained study
      participants. Future studies may show whether further refinements of such
      training programmes will result in statistically significantly better results in
      surgical outcome parameters.

PMID- 14641263
TI  - Corneal penetration of levofloxacin into the human aqueous humour: a comparison
      with ciprofloxacin.
AB  - PURPOSE: To compare aqueous humour levels of levofloxacin and ciprofloxacin
      following topical application to patients scheduled for cataract surgery.
      METHODS: A total of 59 patients undergoing cataract surgery were randomly
      assigned to topical treatment with either levofloxacin 0.5% or ciprofloxacin 0.3%
      eye drops, at one drop every 15 min for four doses immediately prior to surgery.
      Aqueous humour samples were collected by paracentesis and analysed for drug
      content. RESULTS: The (geometric) mean aqueous humour concentration of
      levofloxacin was 0.728 microg/ml; that of ciprofloxacin was 0.080 microg/ml.
      CONCLUSIONS: Levofloxacin achieves 9.1 times the aqueous humour concentration of
      ciprofloxacin. It could be considered a better choice than ofloxacin or
      ciprofloxacin for topical ophthalmic use.

PMID- 14641262
TI  - Clinical evaluation of an eccentric infrared photorefractor: the PowerRefractor.
AB  - PURPOSE: To evaluate the viability of the PowerRefractor as a screening tool for
      examining refractive errors in large samples of children. METHODS: The
      variability of the PowerRefractor was estimated using four patients. The
      refractive error was determined using cyclopentolate and tropicamide as
      cycloplegic agents and compared to that determined in a non-cycloplegic
      situation. In a second study, the data provided by the PowerRefractor were
      compared to results obtained by autorefractor or retinoscopy for 150 children
      aged from 6 months to 5 years. RESULTS: Variability study. Statistical analysis
      showed a statistically significant difference between cycloplegic and non
      cycloplegic refraction for spherical and cylindrical refractive errors (p<0.0001
      in all cases). There was no significant difference between the measurements made
      using tropicamide and cyclopentolate (p=0.33 and p=0.18, respectively).
      Comparison study. In 142 of 150 patients the difference between data obtained by
      the PowerRefractor and an autorefractor was within 1 D (spherical equivalent).
      However, there was a considerable difference between the data generated by the
      two methods in the remaining eight patients (up to 16 D). CONCLUSIONS: The
      PowerRefractor proved to be a reliable tool for estimating refractive errors in
      young children. The apparatus is easy to handle and the simultaneous examination
      of both eyes makes the PowerRefractor ideal for obtaining data on refractive
      errors in large samples.

PMID- 14641264
TI  - Outcome of zone 1 retinopathy of prematurity.
AB  - PURPOSE: To describe the outcome in a series of patients with pre-threshold and
      threshold zone 1 retinopathy of prematurity. METHODS: We performed a
      retrospective analysis of 12 babies, 24 eyes, with zone 1 retinopathy of
      prematurity, treated between 1992 and 2002 with diode laser treatment. RESULTS:
      Ten out of the 12 babies had an unfavourable outcome. The only patients with
      successful anatomical outcomes were those treated before threshold disease
      occurred. All babies had developmental delay or neurological disability.
      CONCLUSION: Zone 1 retinopathy of prematurity has a poor anatomical and visual
      prognosis and many of the babies in our study had developmental delay and
      neurological disability. Earlier treatment may improve the visual outcome.

PMID- 14641265
TI  - The influence of sex hormones on ocular blood flow in women.
AB  - PURPOSE: To investigate the influence of sex hormones on ocular haemodynamics,
      blood flow velocities in the ophthalmic and central retinal arteries and serum
      levels of sex hormones were measured in pre- and postmenopausal women. METHODS:
      Colour Doppler imaging (CDI) was used to determine the flow velocities (peak
      systolic velocity [PSV] and end-diastolic velocity [EDV]) and the resistive index
      (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32
      postmenopausal women, who had never received hormone replacement therapy. Serum
      levels were measured for oestradiol, free testosterone and follicle-stimulating
      hormone. The CDI parameters were compared between the two groups and the
      influence of serum levels of oestradiol and testosterone on blood flow velocities
      and the resistive indices were analysed. RESULTS: After correcting for age and
      mean arterial blood pressure, an analysis of covariance disclosed a significantly
      lower EDV (p=0.02) and a significantly higher RI (p=0.01) in the central retinal
      artery of postmenopausal women compared with premenopausal women. Partial
      correlation analysis, controlling for age, revealed significant correlations
      between the CDI parameters and serum levels of oestradiol and testosterone. For
      premenopausal women, PSV (r=0.58, p=0.04) and EDV (r=0.73, p=0.006) in the
      ophthalmic artery correlated positively with serum oestradiol levels. The RI in
      the central retinal artery decreased with increasing oestradiol levels in both
      groups (premenopausal r= -0.40, p=0.04; postmenopausal r= -0.32, p=0.05). Peak
      systolic velocity in the central retinal artery correlated negatively (r= -0.49,
      p=0.04), whereas the RI correlated positively (r=0.53, p=0.02) with testosterone
      levels in the premenopausal group. Postmenopausal women with higher testosterone
      levels had lower EDV (r= -0.53, p=0.007) in the central retinal artery and higher
      RI in both vessels (ophthalmic artery r=0.48, p=0.01; central retinal artery
      r=0.61, p=0.002). CONCLUSION: Our data provide evidence of a relationship between
      serum sex hormone levels and blood flow velocities and resistive indices in
      retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular
      haemodynamics, whereas testosterone may act as an antagonistic to the effects of
      oestrogen.

PMID- 14641266
TI  - Melanoma-associated spongiform scleropathy: biochemical changes and possible
      relation to tumour extension.
AB  - PURPOSE: To investigate biochemical changes of the sclera in eyes with melanoma
      associated spongiform scleropathy (MASS), and to analyse possible relationships
      between these changes and tumour extension. METHODS: Sections from 364 eyes,
      enucleated for choroidal and ciliary body melanoma, were examined for MASS and
      scleral tumour extension. Biochemical analysis was also performed on eight
      scleral specimens with MASS and eight specimens (controls) from morphologically
      normal sclera of the same eyes. The scleral thickness of each specimen was
      measured. Samples were delipidized, dried and weighed. The weight ratios of
      collagen-related amino acids were calculated based on quantitation by liquid
      chromatography. Amounts of glycosaminoglycans (GAGs) were determined by
      electrophoresis. RESULTS: Melanoma-associated spongiform scleropathy was seen in
      140 eyes (38.5%). Tumour scleral extension was observed in 82 eyes. Of these 82
      eyes, 75 (91.5%) had MASS (p<0.05). Biochemically, the majority of the main amino
      acids of the scleral collagen and total proteins were significantly lower in
      areas with MASS than in the control specimens. Specific GAGs and total GAGs were
      found in significantly higher concentrations in areas with MASS than in the
      control specimens. Scleral thickness was also significantly higher in areas with
      MASS than in the control specimens. CONCLUSIONS: The reduced content of collagen
      manifested by decreased amino acids and total proteins indicates collagen
      degradation in the vicinity of the tumour. The concomitant excessive deposition
      of GAGs accumulates water and may cause loosening of the already degraded
      collagen bundles, giving a histopathological picture of MASS. These changes could
      facilitate tumour cell migration and may explain the high incidence of MASS in
      eyes with scleral tumour extension.

PMID- 14641267
TI  - Regulation mechanisms of retinal pigment epithelial cell migration by the TGF
      beta superfamily.
AB  - PURPOSE: To investigate the expression of specific receptors, signal transducers
      and the effect of transforming growth factor-beta (TGF-beta) on retinal pigment
      epithelium (RPE) migration and proliferation. METHODS: Human RPE cell line D407
      was used in all experiments. The effect of TGF-beta on migration and
      proliferation were studied using a wound healing model and [3H]-thymidine
      incorporation, respectively. The expression of RNA related to the TGF-beta
      superfamily receptors and SMAD1-4 were assayed by reverse transcriptase
      polymerase chain reaction (RT-CPR). The effects of TGF-beta on the intracellular
      position of SMAD were studied by immunoperoxidase and immunofluorescence.
      RESULTS: Transforming growth factor-beta 4 nm and activin A 0.36 nm stimulated
      RPE migration. There was no effect on proliferation. RNA for TGF-beta receptors
      types 1 and 2, and SMAD1-4 were detected in RPE culture. Transforming growth
      factor-beta signal transducer SMAD2 but not SMAD1 moved from the cytoplasm to the
      nucleus after TGF-beta stimulation. CONCLUSION: Transforming growth factor-beta
      can regulate RPE cell migration through specific signal transduction pathways.

PMID- 14641268
TI  - The influence of ageing on the insulin signalling system in rat lacrimal and
      salivary glands.
AB  - PURPOSE: Ageing adversely affects the structure and function of lacrimal and
      salivary glands (LG and SG) and leads to marked insulin resistance that
      correlates with reduced insulin signal transduction. The aim of this study was to
      investigate whether ageing affects insulin signal transduction in LG and SG in
      vivo. METHODS: Male Wistar rats aged 20 months and 2 months (control group) were
      compared (n=8/group). Samples were removed under anaesthesia after i.v. injection
      of insulin, homogenized, immunoprecipitated with anti-insulin receptor (IR), Shc
      and STAT-1 antibodies and immunoblotted with antiphosphotyrosine antibody.
      RESULTS: The 20-month-old rats were significantly hyperinsulinaemic and presented
      a reduced rate of blood glucose disappearance in response to insulin, compared to
      the 2-month-old rats. The level of phosphorylation determined by densitometry in
      the older group of rats showed that ageing significantly reduced insulin-induced
      IR phosphorylation in LG and SG and STAT-1 phosphorylation in SG, compared to in
      the control group, but did not alter Shc phosphorylation. CONCLUSIONS: Ageing
      influences insulin signal transduction in the LG and SG of rats. Considering the
      major anabolic actions of insulin, these observations may help to explain the
      mechanisms of LG and SG dysfunctions observed in ageing.

PMID- 14641269
TI  - Recurrent subretinal haemorrhages and progressive lacquer cracks in a high myope.

PMID- 14641270
TI  - Intravitreal triamcinolone acetonide for the treatment of chronic pseudophakic
      cystoid macular oedema.
AB  - PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide for
      chronic pseudophakic cystoid macular oedema (CME) resistant to medical treatment.
      METHODS: Six eyes of six patients with chronic pseudophakic CME, aged 58-74 years
      (average 66 years), made up the study population. All eyes had persistent CME
      despite having received medical treatment for at least 3 months. Intravitreal
      injection of 4 mg (0.1 ml) triamcinolone acetonide was offered to treat macular
      oedema. The visual and anatomic responses were observed as well as potential
      complications related to the injection procedure and corticosteroid medication.
      RESULTS: The follow-up period was between 6 and 10 months (mean 8.5 months).
      Baseline central macular thickness averaged 504 microm. At 1 month, a reduction
      in the mean central macular thickness of 52% from 504 microm to 264 microm was
      obtained. At 3 and 6 months, the mean central macular thicknesses were 240 microm
      and 232 microm, respectively. Five of the six eyes maintained a visual gain of 15
      or more letters from baseline at 6 months. During follow-up no patient had
      intraocular pressure (IOP) exceeding 21 mmHg. No injection-related complications
      were encountered. CONCLUSIONS: Intravitreal triamcinolone acetonide is a
      promising therapeutic method for chronic pseudophakic CME resistant to medical
      treatment. Further study with a longer follow-up period and larger series is
      warranted to assess the treatment's longterm efficacy and safety and the need for
      retreatment.

PMID- 14641271
TI  - Neuroretinitis associated with cat-scratch disease in Japanese patients.
AB  - PURPOSE: To clarify the prevalence and clinical profile of neuroretinitis
      associated with cat-scratch disease (CSD) in Japan. METHODS: Japanese patients
      were searched using a computer web site, Japana Centra Revuo Medicina. Location
      of patients, medical history, systemic and intraocular findings, treatments and
      visual outcome were examined. RESULTS: We reviewed 15 eyes of 14 patients,
      including our own case. Incidences of the disease were more common in summer than
      in winter and presented in the warmer parts of Japan. All patients had been
      previously healthy and had been exposed to cats or flea bites. Of the 14
      patients, 13 (93%) had febrile illness and seven of these (54%) had
      lymphadenopathy. Uveitis and macular stars were observed in 11 of 15 eyes (73%).
      Most patients were treated with antibiotics and systemic steroids and visual
      prognoses were good. CONCLUSIONS: The clinical features of CSD-associated
      neuroretinitis in Japan are similar to those in other countries. Its distribution
      may correlate with the prevalence of Bartonella henselae-seropositive cats in
      Japan.

PMID- 14641272
TI  - Amnion-shielded trabeculectomy.

PMID- 14641273
TI  - Infectious crystalline keratopathy histopathological characteristics.

PMID- 14641274
TI  - The immediate approach anterior capsulorhexis (IAAC) in cataract surgery:
      contribution to safety and efficacy.

PMID- 14641275
TI  - Early onset versus delayed onset capsular blockage syndrome.

PMID- 14641276
TI  - Intravitreal crystalline triamcinolone acetonide as an additional tool in pars
      plana vitrectomy for complicated proliferative vitreoretinopathy?

PMID- 14641277
TI  - Prepapillary venous loops and choroidal veins tortuosity.

PMID- 14641278
TI  - A 7-year follow-up of severe ocular trauma following a bomb explosion.

PMID- 14641279
TI  - Filamentary keratitis improved by blepharoptosis surgery: two cases.

PMID- 14641280
TI  - Detection of the Epstein-Barr virus genome in the anterior chamber of a patient
      with chronic keratouveitis.

PMID- 14641281
TI  - Mitomycin C trabeculectomy in an eye with cicatricial conjunctiva following
      amniotic membrane transplantation.

PMID- 14641282
TI  - Transscleral cyclophotocoagulation versus cyclocryotherapy in treatment of
      neovascular glaucoma: a retrospective analysis.

PMID- 14641283
TI  - Did squinting cause the 'Durerblick'?

PMID- 14641288
TI  - Gastroesophageal reflux before and after Helicobacter pylori eradication. A
      prospective study using ambulatory 24-h esophageal pH monitoring.
AB  - The aim of this study was to assess prevalence of GERD before and after
      Helicobacter pylori (HP) eradication utilizing 24-h esophageal pH/manometry
      studies. Helicobacter pylori status was confirmed by the Campylobacter like
      organism test. Those testing positive underwent 24-h pH/manometry followed by HP
      eradication therapy and urea breath test. Patients were followed up at 6 months
      and then at 1 year when they underwent a repeat 24-h pH/manometry. Twenty
      patients, 10 with non-ulcer dyspepsia (NUD) and 10 with duodenal ulcer (DU) were
      enrolled, though only 10 patients attended for a repeat 24-h pH/manometry study.
      The patients were well matched, though patients with NUD had a significantly
      higher symptom score at entry compared with the DU group (8.5 vs 5.7, P < 0.05).
      The pH and esophageal manometry data were similar in the two groups. Overall nine
      patients (45%; DU = 5, NUD = 4) had evidence of GERD prior to HP eradication and
      it persisted one year after cure of the infection. The reflux disease occurred in
      the presence of normal LES pressure (mean 15.6 +/- 3.3 mmHg). New onset GERD was
      uncommon after cure of HP infection, occurring in only one patient with NUD.
      Overall HP eradication had no impact on percentage of time pH < 4 (4.69 +/- 3 vs
      4.79 +/- 3), episodes > 5 min (9.8 +/- 16 vs 15.5 +/- 25.3) and Johnson DeMeester
      Score (16.8 +/- 7.5 vs 26.8 +/- 18). In addition successful cure of HP produced
      no significant changes in LES pressure (17.9 +/- 3.8 mmHg vs 19.3 +/- 4.6 mmHg),
      and other esophageal manometry data. Half of HP-positive patients with NUD and DU
      have evidence of GERD before HP eradication. This persists after successful cure
      of the infection. New onset GERD occurs very uncommonly one year after HP
      eradication.

PMID- 14641289
TI  - Barrett's esophagus: combined treatment using argon plasma coagulation and
      laparoscopic antireflux surgery.
AB  - The treatment of Barrett's esophagus is still controversial. Actually, the only
      method to prevent the development to cancer is endoscopic surveillance, which
      ensures good results in terms of long-term survival. An ideal treatment capable
      of destroying columnar metaplasia, followed by squamous epithelium regeneration
      could potentially result in a decrease of the incidence of adenocarcinoma.
      Recently most ablative techniques were used, such as photodynamic therapy,
      ablation therapy with Nd-YAG laser or argon plasma coagulation and endoscopic
      mucosal resection. We started a prospective study in January 1998, enrolling 94
      patients affected by Barrett's esophagus and candidates for antireflux repair in
      order to assess the effectiveness and the results of endoscopic coagulation with
      argon plasma combined with surgery in the treatment of uncomplicated Barrett's
      esophagus. All patients underwent endoscopic treatment with argon plasma; we
      observed complete response in 68 patients (72.34%), 27 of them (39.7%) underwent
      antireflux surgery and the other 41 continued medical therapy. Post-operatively
      19 patients (70%) underwent regular surveillance endoscopies and in two cases
      metaplasia recurred. The final objective of these combined treatments should be
      the complete eradication of metaplastic mucosa. Our experience was that argon
      plasma coagulation combined with antireflux surgery or proton pump inhibitor
      therapy gave satisfactory results, even if follow-up is too short to evaluate the
      potential evolution of metaplasia to cancer. For this reason, we recommend that
      this technique should be done only in specialized centres and that these patients
      continue their endoscopic surveillance program.

PMID- 14641290
TI  - Heller's esophagomyotomy with or without a 360 degrees floppy Nissen
      fundoplication for achalasia. Long-term results from a prospective randomized
      study.
AB  - Heller's esophagomyotomy relieves dysphagia but does not restore esophageal
      peristalsis. The myotomy may induce reflux and the addition of a 360 degrees
      fundoplication may be hazardous with regard to the remaining aperistaltic
      esophagus. The aim of this prospectively randomized clinical trial was to compare
      the outcome for patients with uncomplicated achalasia who underwent an anterior
      Heller's esophagomyotomy (H group) with or without an additional floppy Nissen
      fundoplication (H + N group). Between 1984 and 1995, 20 patients were
      prospectively randomized to one or other of the performed operations, 10 patients
      per group. Esophagitis including Barrett's esophagus (n = 2) was seen under
      medical treatment, in 6 of 9 in the H group but none in the H + N group. No
      patient in the H + N group required postoperative continuous acid-reducing drugs.
      Twenty-four-hour esophageal pH-studies in median 3.4 years after surgery showed
      pathological reflux expressed as a percentage of time below pH 4 of 13.1% in the
      H group compared to 0.15% (P < 0.001) in H + N group. One patient with recurrent
      dysphagia in the H + N group later had an esophagectomy. The remaining patients
      reported significant improvement of dysphagia without symptoms of reflux at 8.0
      years follow-up. Heller's esophagomyotomy eliminates dysphagia, but can induce
      advanced reflux that requires medical treatment. The addition of a 360 degrees
      fundoplication eliminates reflux without adding dysphagia in the majority of
      patients and can be recommended for most patients with uncomplicated achalasia.

PMID- 14641291
TI  - Prokinetic effect of cisapride on pedicled stomach, small bowel and colon grafts
      replacing the esophagus after esophageal resection.
AB  - Cisapride is a potent third generation prokinetic agent acting on postganglionic
      receptors by increasing the release of acetylcholine. In a prospective, self
      controlled study the prokinetic action of cisapride was tested on pedicled
      stomach, jejunum and colon grafts used for substitute after esophageal resection.
      Between 1995 and 1998 15 patients with gastric pull up, 10 patients with colon
      replacement or bypass and eight patients with free jejunum transplant or jejunum
      replacement were evaluated. Esophageal transit scintigraphy was performed before
      and after cisapride administration. From the time-activity curves, the half-life
      of radiolabeled bolus in the esophagus was calculated and preadministration and
      postadministration half-lives were compared. Cisapride significantly reduced the
      half-life of radiolabeled bolus in the substitute in the case of stomach and
      jejunum replacement, while for colon replacement the results were dispersed too
      widely to yield significant difference. Cisapride exerts prokinetic effect on
      pedicled stomach and jejunum substitutes after esophageal resection.

PMID- 14641292
TI  - Multiport staging laparoscopy in esophageal and cardiac carcinoma.
AB  - Between February 1993 and September 2000, 320 patients with esophageal cancer
      were referred to our oesophagogastric unit. One hundred and thirty-three
      consecutive patients with histologically proven carcinoma of the esophagus were
      assessed with a view to resection using multiport staging laparoscopy. Multiport
      staging laparoscopy was performed as a short stay/day case procedure in 133
      patients with esophageal and oesophagogastric junctional carcinoma. Multiple
      ports were used to inspect the liver, omentum, peritoneal surfaces, coeliac/left
      gastric lymph nodes and obtain biopsies and cytology. Satisfactory assessment was
      possible in 127 cases (95%). Laparoscopy detected incurable disease in 31
      patients (24%), some of whom had more than one contraindication to surgery,
      including hepatic metastases (n = 10), peritoneal metastases (n = 12) and
      malignant small volume ascites (n = 5). Lymph node metastases were confirmed
      histologically by biopsy at laparoscopy in 26 patients (fixed nodes, n = 14;
      mobile nodes, n = 12). Sensitivity for the detection of liver and peritoneal
      metastases was 100%, and lymph node metastases were 83%. Specificity for
      detection of hepatic metastases was 99%, 100% for peritoneal metastases and 82%
      for lymph node metastases. Ninety-nine patients proceeded to definitive surgery
      and only two were unresectable. Multiport laparoscopic assessment of metastases
      in patients with esophageal carcinoma avoids unnecessary surgery and allows for
      more efficient use of theatre and intensive care time.

PMID- 14641293
TI  - Mutation of the p53 gene predicts lymph node metastases in Japanese patients with
      esophageal carcinoma: DNA and immunohistochemical analyses.
AB  - We evaluated the clinicopathologic significance of p53 gene mutations, including
      a comparison of DNA analysis and immunohistochemical examination, in Japanese
      patients with esophageal squamous cell carcinoma, a highly aggressive cancer.
      Genomic DNA isolated from 76 tumors without preoperative treatment was subjected
      to polymerase chain reaction and sequencing. Associations were sought between p53
      mutations and clinicopathologic characteristics. Cases also were investigated
      immunohistochemically to detect abnormal p53 protein accumulation. Overexpression
      of p53 protein occurred in 51 cases (67.1%), while gene mutations in the examined
      exons were found in only 14 (18.4%). By multivariate analysis, p53 mutation
      predicted detection of eight or more lymph node metastases. Mutations of the p53
      gene may not only participate in the initiation of esophageal cancer, but also
      may promote lymph node metastasis. Unlike gene mutations, p53 protein
      overexpression did not predict nodal metastasis extent.

PMID- 14641294
TI  - High level concentration of pyrimidine nucleoside phosphorylase in esophageal
      squamous cell carcinoma but no correlation with clinicopathological parameters.
AB  - Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine
      to 5'-fluorouracil, which exerts an anticancer effect before being catabolized by
      dihydropyrimidine dehydrogenase (DPD). Recently, PyNPase has been shown to be
      identical to a potent angiogenic factor, platelet-derived endothelial cell growth
      factor. We analyzed the concentration of PyNPase and DPD in 33 patients with
      esophageal squamous cell carcinoma in fresh-frozen samples by enzyme-linked
      immunosorbent assay. In addition, we evaluated the clinical significance and
      prognostic value of PyNPase expression in esophageal carcinoma. The PyNPase
      concentration of tumor tissue was statistically higher than that of normal tissue
      of the esophagus (248 +/- 146 U/mg protein vs 73 +/- 63 U/mg protein, P =
      0.0001), whereas DPD showed no difference (90 +/- 62 U/mg protein vs 88 +/- 62
      U/mg protein, P = 0.825). The ratio of PyNPase to DPD of tumor tissue was
      statistically higher than that of normal tissue of the esophagus (3.3 vs 0.95, P
      = 0.0001). There were no significant differences between the group with high
      tumor to normal tissue ratios of PyNPase concentration and the low-ratio group in
      terms of the tumor length, depth, lymph node metastasis, lymph vessel invasion,
      vascular invasion, stage and survival. In conclusion, 5'-deoxy-5-fluorouridine
      may be effective on esophageal carcinoma and PyNPase concentration in esophageal
      carcinoma may not be a useful prognostic marker for patients with esophageal
      squamous cell carcinoma.

PMID- 14641295
TI  - Effects of nitric oxide synthase inhibitor to esophagus in a feline esophagitis
      model.
AB  - The present study explores the effects of nitric oxide synthase inhibitor on
      esophageal motility in a feline model with esophagitis. Perfusion of the
      esophagus with acid produced inflammatory changes of esophageal mucosa. The
      esophageal motility was measured before and after the perfusion. One group of
      cats was given nitric oxide inhibitor orally at the same time as the perfusion of
      acid. The control group was given water instead. Esophagitis impairs the motility
      of the esophagus. However, the esophageal motility of the cats that were given
      nitric oxide synthase inhibitor decreased less than that of the control group.
      The results suggested that during esophagitis there is an alteration of the
      nitric oxide synthase/nitric oxide pathway in the esophagus, which may be one of
      the important mechanisms of esophageal motility dysfunction.

PMID- 14641296
TI  - Telescopic esophageal anastomosis: operative technique, clinical experiences.
AB  - The authors reconstructed the continuity of the alimentary tract by performing
      telescopic esophagogastrostoma in 208 patients who underwent either esophageal
      resection or total gastrectomy. The substance of the telescopic technique is to
      invaginate the distal section of any oral tubular organ to the lumen of an aboral
      tubular one and to fix it there. In case of telescopic esophageal anastomosis a
      10-15 mm long esophageal segment is invaginated into the gastric tube or jejunum.
      A 3-4 mm wide serosal surface of the wall of the distal anastomosing organ straps
      the esophagus circularly. Ninety-six transthoracic and 12 transhiatal
      esophagectomies, 19 partial esophageal resections, four esophageal bypasses, and
      77 total or extended total gastrectomies were reconstructed using telescopic
      anastomosis. Undisturbed healing could be observed in 67 patients after
      esophageal operations and in 46 patients of total gastrectomies. Anastomosis
      leakage occurred in 12 of 108 patients (11.1%) after cervical
      esophagogastrostomy. Leakage could be observed in 7 of 44 patients (15.9%) after
      end to side and in 5 of 64 patients (7.8%) in case of end to end esophago
      gastrostoma. There were no failures after two cases of cervical esophago
      ileocolostoma and 21 of esophagogastrostomas in the thoracic position. All of the
      59 intra-abdominal anastomoses healed without complication. Thirteen of 131
      patients (9.9%) died after esophageal operations and four of 77 (5.2%) after
      gastrectomies. There were no mortal complications due to anastomotic leakage. The
      telescopic anastomosis is a safe alternative method in cases of total gastrectomy
      or esophageal operation.

PMID- 14641297
TI  - A new philosophy in esophageal reconstruction with colon. Thirty-years
      experience.
AB  - The author reports a personal series of 347 patients with colon interposition
      grafting as an esophageal substitute, the majority of them carried out for
      corrosive pharyngoesophageal strictures (284) followed by malignancy (54). A
      personal philosophy is exposed, based on increased flexibility in the choice of
      the type of colic interposition depending on the pattern of blood supply. This
      mobile policy called 'balanced operation' is opposed to the classic rigid
      approach based on the use of a single procedure of esophagocoloplasty. The
      author's choice is the ileocecum with long ileal loop (65 cm), favoring
      preservation of the ileocecal valve, and conferring an antireflux mechanism. In
      particular cases the cecum may be removed and an ileal graft carried out. If this
      arrangement is not feasible one should slide toward the left in a clockwise
      direction performing a left colon interposition (iso- or antiperistaltic).
      Overall mortality was of 16 cases (4.6%). Morbidity is analyzed and different
      particular arrangements like continuous colic loop, superlong graft, Roux-en-Y
      procedure are described. A general outline of pharyngeal reconstruction in
      corrosive strictures is presented.

PMID- 14641298
TI  - Mediastinal bronchial artery aneurysm with hematemesis.
AB  - Mediastinal bronchial artery aneurysm is a rare condition which can lead to
      potentially fatal hemorrhage. In most cases it presents respiratory symptoms due
      to rupture into pleural parenchyma. But when it develops mediodorsally and
      compresses the esophagus, it may cause dysphagia or hematemesis. Here we report a
      case of mediastinal bronchial artery aneurysm which presented with hematemesis.
      Computed tomography and endoscopic ultrasound showed what seemed to be a
      submucosal tumor on the esophagus. We were able to correctly diagnose the
      aneurysm using magnetic resonance imaging and probe thoracoscopy, and were able
      to successfully treat with transluminal artery embolization.

PMID- 14641299
TI  - Esophageal cancer associated with right aortic arch: report of two cases.
AB  - Esophageal carcinoma associated with a right aortic arch is very rare. In such
      cases, the dissection of right paratracheal lymph nodes is difficult. Herein, we
      report two cases of thoracic esophageal carcinoma with right aortic arch, for
      which the left door open method was used to provide a good surgical view.
      Postoperative chemotherapy and radiotherapy were used for both cases and no
      evidence of recurrence or metastasis has been noted in the 24-month postoperative
      period.

PMID- 14641300
TI  - Humoral hypercalcemia of malignancy due to bipartite squamous cell/small cell
      carcinoma of the esophagus immunoreactive for parathyroid hormone related
      protein.
AB  - We report the case of a 63-year-old man who presented with weakness, fatigue,
      dehydration, confusion, abdominal pain, congestive heart failure and
      hypercalcemia. He expired and autopsy revealed an exulcerating carcinoma of the
      esophagus, invading the esophageal wall and metastasizing to the lungs, skin and
      lymph nodes. Histology demonstrated an epithelial tumor consisting of two
      components with transition between the two. One component was a keratinizing
      squamous cell carcinoma, whereas the other component consisted of pleomorphic
      small cells. The hypercalcemia was assumed to be due to parathyroid hormone
      related protein (PHRP), which was demonstrated by immunohistochemistry only in
      the pleomorphic small cells and not in the squamous cells. PHRP induced humoral
      hypercalcemia of malignancy is most often associated with squamous cell
      carcinomas. The finding that in our case, the pleomorphic small cell component
      was PHRP immunopositive and the squamous cell component showed no
      immunoreactivity, is intriguing and remains unexplained.

PMID- 14641301
TI  - Thoracoscopic enucleation of a leiomyoma of the upper thoracic esophagus.
AB  - The authors present two cases of leiomyoma of the upper esophagus. Both of the
      cases presented with dysphagia, and one patient complained of pyrosis. An upper
      gastrointestinal endoscopy showed midesophageal narrowing without mucosal
      irregularity, suggestive of leiomyoma. The patients were successfully treated by
      thoracoscopic enucleation of the leiomyoma, using four thoracic trocars. In one
      patient (Case 1), the azygus vein had to be divided. Both of the patients are
      asymptomatic in the late-postoperative period.

PMID- 14641302
TI  - Two cases of superficial basaloid squamous carcinoma of the esophagus.
AB  - . Basaloid squamous carcinoma of the esophagus is very rare. We report two cases
      of basaloid squamous carcinoma of the esophagus. Both tumors histologically
      consisted of solid cell nests with intervening fibromyxoid stroma. In some tumor
      nests were comprised of pseudoglandular structures containing myxoid matrix, and
      displayed focal immunoreactivity for laminin. Thoracic esophagectomy with lymph
      node dissection was followed by intrathoracic esophagogastrostomy in both
      patients. The patients had uneventful postoperative courses. Regular periodic
      follow-up showed no evidence of recurrence or metastasis in the 22-month
      postoperative period.

PMID- 14641303
TI  - Delayed aortic rupture after radiochemotherapy and esophagectomy for esophageal
      cancer.
AB  - Spontaneous rupture of major vessels is a known though rare complication in
      treatment of patients with esophageal cancer, but its pathophysiology is not very
      well understood. We herein report about the sudden death of a 42-year-old man due
      to spontaneous aortic rupture, 11 days after transthoracic esophagectomy. Because
      of a locally advanced squamous cell carcinoma of the distal esophagus, which was
      considered irresectable at the time of presentation, the patient had received one
      course of chemotherapy followed by synchronous chemoradiation (60 Gy, 5
      fluorouracil and cisplatin) prior to surgery. We discuss the patho-anatomic
      findings of the postmortem examination concerning alterations of the aortic wall
      and the potential correlations with aggressive radiochemotherapy protocols.

PMID- 14641304
TI  - Isolated esophageal atresia and perinatal risk factors.

PMID- 14641306
TI  - Chemoprevention for Barrett's esophagus trial. Design and outcome measures.
AB  - Barrett's esophagus is a premalignant condition in which normal squamous
      epithelium of the esophagus is replaced by metaplastic columnar epithelium. It is
      a known risk factor for the development of esophageal adenocarcinoma. With the
      incidence of esophageal adenocarcinoma rising, it is reasonable to study
      Barrett's esophagus as a potential target for therapy that may prevent, delay
      and/or reverse ongoing tumorigenic processes. Epidemiologic and animal studies
      support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the
      chemoprevention of several cancers, including esophageal cancer. Cyclo-oxygenase
      2 (COX-2) inhibitors are a new class of NSAIDs that inhibit prostaglandin
      synthesis by selectively blocking the COX-2 enzyme. The COX-2 enzyme has been
      reported to be over-expressed in premalignant and malignant states, including in
      Barrett's esophagus and esophageal adenocarcinoma. The Chemoprevention for
      Barrett's Esophagus Trial (CBET) is a phase IIb, multicenter, randomized, double
      masked, placebo-controlled study of the selective COX-2 inhibitor, celecoxib, in
      patients with Barrett's dysplasia. The sample size is 200 patients with high or
      low grade Barrett's dysplasia. Celecoxib is administered orally, 200 mg twice per
      day; the dosing schedule for placebo is the same. Randomization is stratified by
      dysplasia grade and by clinic. Endoscopy with biopsies is performed at specified
      time intervals according to the highest grade of dysplasia determined at
      randomization. The primary outcome measure is the change from baseline to 1 year
      in the proportion of biopsies exhibiting dysplasia. Secondary outcomes include
      change from baseline in the maximal grade, extent and surface area of dysplasia.
      Tertiary outcomes will include measurements of various relevant biomarkers.

PMID- 14641307
TI  - Utility of esophageal biopsy in the diagnosis of nonerosive reflux disease.
AB  - This study evaluated the accuracy of esophageal biopsy for the diagnosis of
      nonerosive reflux disease (NERD) in adults. Thirty-five patients with reflux
      symptoms and a normal endoscopy were prospectively evaluated using esophageal
      biopsies, 24-h ambulatory pH monitoring and symptomatic response 4 weeks after an
      increase in antireflux therapy. Biopsies were scored for the total number of
      typical histologic reflux features seen. Patients were considered to have NERD if
      both pH-metry was positive and step-up therapy was successful. Biopsies were then
      compared to this predefined gold standard. Biopsy was most sensitive (62%) but
      poorly specific (27%) when one or more histologic reflux features were seen. A
      threshold of three or more histologic features improved the specificity (91%) but
      reduced sensitivity (31%). Response to step-up therapy was associated with 100%
      sensitivity and 100% negative predictive value when compared to biopsy and pH
      metry as an alternate combined gold standard. In conclusion, biopsy is
      insensitive in diagnosing NERD but reasonably specific if three or more typical
      histologic reflux features are present.

PMID- 14641308
TI  - Efficacy of esomeprazole in controlling reflux symptoms, intraesophageal, and
      intragastric pH in patients with Barrett's esophagus.
AB  - Barrett's esophagus is a metaplastic condition associated with gastroesophageal
      reflux disease and an increased risk for adenocarcinoma. Acid plays a significant
      role in the development and progression of Barrett's esophagus and high dose
      proton pump inhibitor (PPI) therapy is often needed. The aim of this study is to
      assess the efficacy of esomeprazole, a new potent PPI, on symptom relief and
      intraesophageal and intragastric acid suppression in patients with Barrett's
      esophagus (BE). Patients were evaluated by standardized questionnaires and dual
      sensor 24-h pH monitoring while receiving esomeprazole at a dose (40-80 mg/day)
      needed for control of symptoms. Analyses of intraesophageal and intragastric pH
      profiles were then made. Thirteen patients, mostly men, were studied. All
      tolerated esomeprazole (40-80 mg/day) with good symptom control. Sixty-two
      percent of patients with BE had abnormal intraesophageal pH profiles despite
      adequate symptom control on esomeprazole which was associated with significant
      breakthrough of intraesophageal acid control, particularly at night. Low
      nocturnal intragastric pH correlated highly with nocturnal intraesophageal acid
      reflux (P = 0.004) and there was a relative failure of nocturnal intragastric
      acid control with esomeprazole. A high percentage of patients with BE continue to
      exhibit pathologic GERD and low intragastric pH despite esomeprazole for reflux
      symptom control. For an antisecretory treatment aimed at chemoprevention of
      esophageal adenocarcinoma to be effective, higher PPI dosing confirmed by pH
      monitoring may be necessary.

PMID- 14641309
TI  - Impaired visceral sensitivity to acid reflux in patients with Barrett's
      esophagus. The role of esophageal motility*.
AB  - Patients with Barrett's esophagus have been reported to have impaired visceral
      sensitivity to acid perfusion and distension compared with non-Barrett's
      refluxers, but the mechanism is poorly understood. Esophageal motility and
      clearance mechanisms may be important, and this study explored the relationship
      of motility with symptoms. Seventy-four patients with Barrett's esophagus were
      compared with 216 patients with gastro-esophageal reflux disease (GERD) with
      abnormal acid reflux scores, and 50 symptomatic patients who had normal acid
      exposure. All patients had esophageal manometry and 24-h pH monitoring. Thirty
      six Barrett's patients also had 24-h bile reflux monitoring. Symptoms were
      assessed by Symptom Index (SI) during 24-h pH monitoring. Barrett's patients with
      normal motility had a significantly lower SI than GERD patients for similar acid
      exposure (P < 0.001). Barrett's patients with abnormal motility had higher acid
      exposure than those with normal motility (P < 0.05), but the SI values for this
      group was not significantly different from the GERD patients. SI and Bile reflux
      in Barrett's esophagus was not significantly different in patients with normal or
      abnormal motility. Barrett's patients had less sensitivity than GERD patients for
      similar acid exposure. Normal motility in Barrett's esophagus is associated with
      the poorest sensitivity and the presence of increased acid exposure is required
      in order to achieve sensitivity levels comparable with GERD patients.

PMID- 14641310
TI  - Treatment of patients with achalasia with botulinum toxin: a multicenter
      prospective cohort study.
AB  - Botulinum toxin (BT) injection is an alternative treatment of achalasia. The aim
      of the study was to examine outcomes of patients treated with BT in the Czech
      Republic. Since 1997, 49 patients with achalasia have been treated with BT. We
      prospectively evaluated the effect of BT injection on 41 patients during a median
      follow-up of 24 months (range 9-62). Esophageal manometry was performed before
      and at 3-5 months after the injection. In 16 patients, BT was injected from the
      antegrade angle only (subgroup A), in 15 patients, BT was injected from both
      retrograde and antegrade angles (subgroup B) and, in 10 patients, BT injection
      was combined with subsequent balloon dilatation (subgroup C). Immediate clinical
      response was achieved in 93% of patients. Clinical remission was sustained beyond
      3 months in 83% of patients (responders). Fourteen responders (41%) did not
      experience a relapse during the median of 22 months. Twenty responders (59%)
      experienced symptomatic relapse approximately 8 months after the injection. Ten
      relapsers underwent BT reinjection, five (50%) of them were asymptomatic for
      another 14 months. The remaining five (50%) patients reported a second relapse
      approximately 6 months after the reinjection. Median duration of the symptom-free
      period was 11.5 months after the first BT injection, and 10.5 months after the
      second (P = 0.21). We did not find any significant predictor of a favorable
      outcome; responders tended to be older and to have a lower basal lower-esophageal
      sphincter pressure. Patients in subgroup C were more likely to be in remission at
      1 and 2 years as compared with patients in subgroup A. BT injection is an
      effective treatment of achalasia in the short term. However, almost 70% of
      patients experience a relapse within 2 years. BT injection should therefore be
      reserved for patients at risk for more invasive procedures or for patients who
      prefer this treatment.

PMID- 14641311
TI  - Paraesophageal hiatal hernias in children.
AB  - Hiatal hernia is a rare condition, which may be a cause of important clinical
      problems either as a mediastinal mass or as a cause of failure of the antireflux
      mechanism. Nineteen patients treated for paraesophageal hiatal hernias were
      included in the study. We investigated demographic data, diagnostic studies and
      symptoms of the patients together with the type of operation and outcome.
      Respiratory and gastrointestinal complaints were the prominent symptoms in most
      patients. Plain X-ray, contrast radiological study and esophagoscopy were used in
      the diagnostic workup. Surgical repair was performed via thoracic, abdominal or
      thoraco-abdominal approaches. Concomitant antireflux procedures were performed in
      13 patients. Hiatal hernias in children may be asymptomatic or may present with a
      variety of symptoms or dramatic complications. Because of the risk of
      complications, surgical treatment is necessary shortly after diagnosis. Repair of
      the hiatus combined with antireflux surgery seems to yield satisfactory results.

PMID- 14641312
TI  - K-ras codon 12 mutations of the super-minute dysplasia in Barrett's esophagus by
      DNA extraction using a microdissection method.
AB  - The aim of this study was to clarify the histogenesis of Barrett's cancer. First,
      28 lesions of the super-minute dysplasia <or= 1 mm in diameter were detected by
      pathological examinations for Barrett's esophagus. Secondly, the K-ras codon 12
      mutations in these super-minute neoplasias of the Barrett's esophagus were
      examined by DNA extraction using a microdissection. It was found that seven of 28
      (25%) super-minute dysplasia lesions in the Barrett's esophagus showed K-ras
      mutation, and were a single mutation, with AGT being detected in three lesions
      and GAT being detected in four lesions. Also, these dysplasia lesions could be
      divided into two groups according to p53-LI. Two among three lesions with p53-LI
      over 90%, which were considered to be morphologically high grade dysplasia or
      intramucosal adenocarcinoma, showed K-ras mutations (both lesions: GGT-->AGT),
      and 5 among 25 lesions with an average p53-LI of 58%, which were considered to be
      morphologically low grade dysplasia, showed K-ras mutation (four lesions: GGT-
      >GAT, 1 lesion: GGT-->AGT). This current study shows that some dysplasia lesions
      have K-ras mutations in their initial condition, whether these atypical tubule
      lesions are low grade dysplasia or high grade dysplasia (intramucosal
      adenocarcinoma), and supports the dysplasia-carcinoma sequence in the
      histogenesis of Barrett's cancer and synchronously suggests that there is a
      different route to it.

PMID- 14641313
TI  - Oral immune tolerance to tumor specific antigens may confer growth advantage to
      esophageal and gastric cancers.
AB  - Oral administration of antigens induces antigen-specific systemic immune
      tolerance (Oral Tolerance). We postulate that the poorer prognosis of foregut
      cancers might, in part be explained by the systemic immune tolerizing effect of
      tumor specific antigens shed into and processed by the gut immune system thus
      conferring a growth advantage specific to individual cancers. Immunocompetent
      Balb/c mice were fed by gavage, either tumor tissue (JBS/CarB) in phosphate
      buffered saline (PBS) or PBS alone, daily for 14 days. On day 15 either
      subcutaneous tumors were induced or animals were immunized with cells in
      adjuvant. JBS tumors appeared earlier and grew faster in the JBS tumor fed mice
      than in either the PBS (P = 0.025) or CarB (P = 0.168) fed animals. The delayed
      type hypersensitivity response in tolerized mice was significantly abrogated (P <
      0.01) compared to controls. These experiments demonstrate antigen specific oral
      immune tolerance for tumors, which is reflected in a faster growth rate and
      impaired delayed type hypersensitivity response. Similar mechanisms may be
      operational in human esophagogastric malignancy and may in part explain their
      poorer outcome.

PMID- 14641314
TI  - Association between esophageal squamous cell carcinoma and human papillomavirus
      detected by Hybrid Capture II assay.
AB  - From July 1999 to July 2000, 40 patients from the Surgical Oncology and
      Gastroenterology Departments of Irmandade da Santa Casa de Misericordia de Porto
      Alegre were enrolled in a prospective study in order to find the frequency of
      human papillomavirus DNA (HPV-DNA) in esophageal squamous cell carcinoma. They
      were compared to 10 normal individuals (controls). Digene Inc. (Digene
      Corporation, Gaithersburg MD, USA) Hybrid Capture II assay, a chemoluminescent
      method, was used in both groups. The samples were collected from the tumor group
      by endoscopic biopsy in 20 cases, and by surgical specimens in the other 20
      cases; the control group all underwent endoscopic biopsies. The cut-off point in
      the analytical assay for HPV-DNA was 1.0 pg/mL. Digene Corp. Hybrid Capture II
      assay tests HPV-DNA and differentiates high and low-risk for malignization virus
      groups. Gender, age, location of the tumor in esophagus and degree of
      differentiation on histology were also analyzed. There was one positive case
      (1.14 pg/mL), a 2.5% frequency of low-risk HPV-DNA type in the esophageal
      squamous cell carcinoma group (CI 95%: 0.00-7.34%). This group of patients
      consisted of 30 male and 10 female individuals, similar to the distribution seen
      in large series of such patients from the Brazilian population. The mean age was
      63 years. Endoscopic samples of 10 patients who underwent endoscopic biopsy
      procedure for aleatory reasons, with normal looking esophageal mucosa, were
      tested to detect HPV-DNA, as controls. There was one positive case (1.17 pg/mL)
      of high-risk HPV-DNA type, resulting in a 10% positive rate. HPV-DNA is rarely
      found in esophageal squamous cell carcinomas: we found a 2.5% frequency, with
      confidence interval of 0-7.34%; and this is in the same range of controls (10%
      frequency, with CI: 9.1-10.9%). Both patients had a viral load quite near the 1.0
      pg/mL cut-off point.

PMID- 14641315
TI  - Experimental examination of the healing process of telescopic esophageal
      anastomosis.
AB  - The basis of telescopic anastomosis is old, only the practical details of it have
      changed and improved. The telescopic anastomosis technique is successfully
      applied in our practice for reconstruction of gastrectomy and esophageal
      resection. The reason for this study was that data about the healing process of
      telescopic anastomosis had not been found in the literature. We used four groups
      of mongrel dogs for our experiments: Group A (n = 3) received 20 mm-long
      invaginations with a survival time of 7 days; Group B (n = 3) received 10 mm-long
      invaginations with a survival time of 21 days; Group C (n = 3) received 20 mm
      long invaginations with a survival time of 21 days; Group D (n = 3) received 30
      mm-long invaginations with a survival time of 21 days. At the end of the above
      survival times we removed the anastomosing area, measured the bursting pressures
      and performed morphological and histological examinations. In each case we also
      performed an anastomosis exactly the same as a completely healed anastomosis and
      its pressure tolerance was measured (0 day). The pressure tolerance within the
      anastomosis rises gradually and independently of the length of the invaginated
      esophageal part. Anastomosis leakage did not occur. The invaginated esophageal
      part did not suffer any damage. The muscular wall of the intragastric part of the
      esophagus became covered by the mucosa of the stomach during the healing process
      and it joined with the esophageal mucosa at the edge of the free end of the
      esophagus.

PMID- 14641316
TI  - Comparative anatomical study of the anterior and posterior mediastinum as access
      routes after esophagectomy.
AB  - Esophagectomy is the main option for treatment of esophageal cancer. Among the
      subjects of surgical interest is the use of anterior versus posterior mediastinum
      to permit reconstruction of the alimentary tract. We performed postmortem
      measurements in order to analyze the lengths of both routes. For each route
      (anterior and posterior) we performed two measurements. The first one was called
      anatomical route and the second was named as surgical route. Both routes begin at
      the cricoid cartilage. The anatomical route goes to the celiac axis and the
      surgical route goes to the gastroduodenal artery. Our results show that in both
      routes the posterior mediastinum is a shorter way to reach the cervical region.

PMID- 14641317
TI  - Long-term survivors of advanced esophageal cancer without surgical treatment: a
      multicenter questionnaire survey in Kyushu, Japan.
AB  - Since the introduction of recent improvements in adjuvant therapy for esophageal
      cancer, some patients have demonstrated good prognosis. In the present study, we
      analyzed 3- and 5-year survivors of advanced esophageal cancer who did not
      undergo any surgical treatment. Between 1990 and 1998, 831 patients were admitted
      to 14 university hospitals and one cancer center associated with the membership
      of the Kyushu study group for adjuvant therapy of esophageal cancer. Twelve
      (1.4%) of the patients were 3-year survivors and 13 (1.6%) were 5-year survivors.
      The reasons for non-operation were refusal (eight patients), tumor-related
      factors (11 patients), and host-related factors (six patients). With a single
      exception, all patients had locally advanced tumors. Almost all long-term
      survivors had fewer than five lymph node metastases, in regions limited to the
      neck and/or mediastinum. Radiation therapy was combined with chemotherapy for 16
      of the 25 patients, and chemotherapy-based cisplatin was used for 15 of these 16
      patients. Fifteen of the patients remain alive; 10 died seven of them from
      esophageal cancer. Chemoradiation therapy was effective for some patients with
      locally advanced esophageal cancer, particularly in the absence of or with few
      lymph node metastases. To improve the prognosis of patients with advanced
      esophageal cancer who, for various causes, cannot undergo surgical treatment, a
      new protocol for adjuvant therapy is required.

PMID- 14641318
TI  - Esophagogastrectomy without pyloroplasty.
AB  - There is no consensus on the need for pyloroplasty after esophagectomy or
      proximal gastrectomy with an esophagogastrostomy and vagotomy. Arguments for
      routine pyloroplasty include prevention of postoperative delayed gastric
      emptying. Arguments against include prevention of postoperative dumping syndrome
      and bile reflux esophagitis. The purpose of this study was to assess clinical
      outcomes of patients undergoing esophagogastrectomy without routine pyloroplasty.
      All patients undergoing esophagogastrectomy or proximal gastrectomy with
      esophagogastrostomy from October 1996 to September 2002, inclusive were reviewed
      for age, gender, diagnosis, type of resection, pathology, short-term
      complications, long-term complications, remedial procedures performed, and
      postoperative gastric emptying scintigraphy. 58 patients were studied.
      Postoperative mortality was 6.9%, and anastomotic leak rate 12.1%. Eleven
      patients (19%) had symptomatic gastroparesis, two required pyloric balloon
      dilation and one a pyloroplasty. No patients complained of dumping symptoms;
      reflux requiring medical intervention occurred in seven (12.1%), and anastomotic
      stricture requiring dilation occurred in five (8.6%). Omitting a pyloroplasty
      does not lead to a high frequency of symptomatic delayed gastric emptying.
      Maintaining the pylorus may protect patients from dumping syndrome, and bile
      reflux esophagitis with its potential noxious effects on the remaining esophageal
      mucosa.

PMID- 14641319
TI  - Validity of intraoperative pathological diagnosis of paratracheal lymph node as a
      strategy for selection of patients for cervical lymph node dissection during
      esophagectomy.
AB  - The aim of this paper is to examine whether intraoperative examination of
      paratracheal nodes can indicate cervical node dissection and whether this
      approach is valid. From 1988 to 1997, 76 patients with thoracic esophageal
      squamous cell carcinoma received esophagectomies with and without cervical lymph
      node (LN) dissection based on the results of intraoperative pathological
      diagnosis from selective checking of paratracheal LN. We retrospectively examined
      the outcomes for the patients and the micro metastasis in the dissected lymph
      node using cytokeratin staining. Three of the seven patients with cervical LN
      dissection were detected as having cervical LN metastasis by postoperative
      hematoxylin-eosin or cytokeratin staining. Five (7%) of the 69 patients without
      cervical LN dissection had cervical LN recurrence after the operation. Four of
      the seven patients who were diagnosed as having metastasis or micro metastasis in
      paratracheal LN by postoperative examination had cervical LN recurrence after the
      operation. In conclusion, the esophagectomy with and without cervical LN
      dissection for thoracic esophageal squamous cell carcinoma based on the results
      of intraoperative pathological diagnosis from selective checking of paratracheal
      LN was not fully acceptable. The reliability of intraoperative pathological
      diagnosis of selective checking may improve by increasing the number of checked
      LN and the detection of micro metastasis.

PMID- 14641320
TI  - Small cell carcinoma of the esophagus; clinicopathological and
      immunohistochemical analysis of six cases.
AB  - Small cell carcinoma arising in the esophagus is a relatively rare disease. In
      the more common small cell carcinoma of the lung, the diagnostic significance of
      several new markers has been recently reported. This study used
      immunohistochemical techniques in addition to clinicopathological analysis, in
      order to clarify the utility of newer markers as biological parameters or as
      diagnostic tools. Six patients with small cell carcinoma of the esophagus were
      clinicopathologically analyzed. Immunohistochemical staining was performed using
      primary antibodies for bombesin, CD56 and CD57 in addition to conventional
      endocrine markers chromogranin A, neuron specific enolase and synaptophysin. All
      patients died within 2 years of surgery due to cancer recurrence, whether or not
      they had received adjuvant therapy. Pathological stages ranged from IIa to IVb
      and lymph node metastasis was observed in five cases. Of the six cases, four
      showed a positive reaction for bombesin and five were positive for CD57. In
      contrast, no cases revealed a positive reaction for CD56. The one case to survive
      24 months after surgery was not shown to express bombesin, CD56 or CD57. Small
      cell carcinoma of the esophagus demonstrated an unfavorable prognosis. The study
      suggested that in this disease, bombesin and CD57 (but not CD56) were useful as
      biological markers, predicting clinical outcome rather than having diagnostic
      significance.

PMID- 14641321
TI  - Aortoesophageal fistula of uncommon origin: perforation of a Barrett's ulcer.
AB  - Aortoesophageal fistulas are life-threatening conditions of which over half are
      secondary to thoracic aortic aneurysms. Four cases related to perforation of a
      Barrett's ulcer have been described so far, accounting for less than 1% of
      published aortoesophageal fistulas. We report a fifth case, which presented with
      severe hypotension, anemia and hematemesis. The patient underwent emergency
      esophagectomy and aortic closure but postoperatively required aortic
      endoprosthesis for residual bleeding. This case highlights the great diagnostic
      and therapeutic challenge associated with perforated Barrett's ulcer.

PMID- 14641322
TI  - Esophageal carcinoma with tracheal stenosis due to tumor invasion and long
      survival after chemoradiotherapy.
AB  - For patients who have esophageal carcinoma with tracheal invasion surgery is
      usually not indicated because operative complications are considerable and the
      prognosis is poor. We experienced complete regression of a large esophageal
      carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal
      fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to
      the lower thoracic esophagus, and was combined with chemotherapy using cisplatin
      and 5-fluorouracil. The tumor decreased markedly in size and the tracheal
      stenosis resolved. The patient has survived for 4 years, although second primary
      early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years
      after his initial chemoradiotherapy. Although the prognosis of advanced
      esophageal carcinoma with invasion of other organs is usually poor, the effect of
      chemoradiotherapy can sometimes be dramatic and a good result can be achieved in
      such patients.

PMID- 14641323
TI  - Mucoepidermoid carcinoma of the esophagus treated by endoscopic mucosal
      resection.
AB  - Mucoepidermoid carcinoma is a mixed cell tumor with both adenocarcinomatous and
      squamous components. We report a rare case of superficial mucoepidermoid
      carcinoma of the esophagus with mucosal gastric cancer. Endoscopic mucosal
      resection was performed on a 67-year-old man with a slight but defined depressed
      lesion of the thoracic esophagus and two lesions of mucosal gastric cancer.
      Histological examination revealed that the lesion of the esophagus was a
      mucoepidermoid carcinoma and the two lesions of the stomach were well
      differentiated adenocarcinoma. Since the mucoepidermoid carcinoma had only
      slightly invaded the submucosal layer, it was thought to arise from the ductal
      epithelium of the esophageal gland or the stratified squamous epithelium of the
      esophagus. Radiation therapy with a total dose of 60 Gy was performed and there
      has been no recurrence or metastasis to other organs during 36 months of follow
      up.

PMID- 14641324
TI  - Intercostal drain migration post esophagectomy.
AB  - A 38-year-old man underwent an Ivor-Lewis esophagectomy for a squamous carcinoma
      at the lower third of his esophagus. On the fifth postoperative day one liter of
      turbid fluid appeared from the intercostal drain and there was a right-sided
      pleural effusion on the chest radiograph. A contrast swallow demonstrated a leak
      at the distal part of the gastric staple line. This leak was managed
      conservatively and subsequent contrast swallows failed to show any leakage
      despite the persistent drainage from the drain. At gastroscopy, the intercostal
      drain was seen to have eroded through the stomach wall. The drain was
      repositioned and the patient was discharged from hospital 5 days later. We
      believe this to be the first report of an intercostal drain migration into the
      stomach after an elective esophagectomy.

PMID- 14641325
TI  - Esophageal involvement as an uncommon modality of relapse of Hodgkin lymphoma.
AB  - We present a case of systemic Hodgkin's lymphoma, relapsed with esophageal
      involvement after 3 years of complete remission. The importance of an accurate
      diagnostic work-up is emphasized. Esophagectomy and chemotherapy followed by bone
      marrow transplantation allowed a complete response and the long-term survival of
      the patient.

PMID- 14641326
TI  - Cellular and molecular mechanisms of development of the external genitalia.
AB  - The limb and external genitalia are appendages of the body wall. Development of
      these structures differs fundamentally in that masculine development of the
      external genitalia is androgen dependent, whereas development of the limb is not.
      Despite this fundamental difference in developmental regulation, epithelial
      mesenchymal interactions play key roles in the development of both structures,
      and similar regulatory molecules are utilized as mediators of morphogenetic cell
      cell interactions during development of both the limb and external genitalia.
      Given the relatively high incidence of hypospadias, a malformation of penile
      development, it is appropriate and timely to review the morphological, endocrine,
      and molecular mechanisms of development of the genital tubercle (GT), the
      precursor of the penis in males and the clitoris in females. Morphological
      observations comparing development of the GT in humans and mouse emphasize the
      validity of the mouse as an animal model of GT development and validate the
      results of experimental studies. Accordingly, the use of mutant mice provides
      important insights into the roles of specific regulatory molecules in development
      of the external genitalia. While our current understanding of the morphological
      and molecular mechanisms of mammalian external genitalia development is still
      rudimentary, this review summarizes the current state of our knowledge and
      whenever possible draws from the rich experimental embryology literature on other
      relevant organs such as the developing limb. Future research on the hormonal and
      molecular mechanisms of GT development may yield strategies to prevent or reduce
      the incidence of hypospadias and to elucidate the molecular genetic mechanisms of
      GT morphogenesis, especially in relation to common organogenetic pathways
      utilized in other organ systems.

PMID- 14641327
TI  - Beyond homeosis--HOX function in morphogenesis and organogenesis.
AB  - Hox genes encode conserved transcription factors expressed along the antero
      posterior axis of vertebrates and invertebrates. In both phyla, HOX proteins
      control the formation of specific structures in the segments where they are
      expressed. Because of the global effect they have on segment morphology, the Hox
      genes are said to control segment identity. Here we review the data available on
      how HOX proteins regulate their downstream targets and how they mediate the
      formation of segment-specific structures. Within the segment, the information
      provided by HOX proteins, tissue-specific transcription factors, and signaling
      pathway effectors becomes integrated at the enhancer of the target genes,
      resulting in their localized activation. In general, HOX proteins regulate the
      morphogenesis of specific organs indirectly by activating networks of
      transcription factors and signaling molecules, but they can also directly
      regulate the so-called realizator genes: genes that control the cell behaviors
      that induce morphogenesis. Here we review some of the Hox-activated networks, the
      most interesting realizator genes known to date, and summarize how organogenesis
      is affected in Hox mutants. These examples reveal that only a fraction of the
      transformations caused by Hox mutations are in fact homeotic (leading to the
      morphological transformation of a structure present in one segment into that
      present in another segment). In the cases where Hox gene mutants do not cause
      homeotic transformations, the wild-type function of the Hox gene is to activate
      specific cell behaviors (cell proliferation, survival, shape changes, and
      rearrangements) that lead to the morphogenesis of particular organs. This second
      non-homeotic function is common to vertebrates and invertebrates, and we argue
      that it may actually constitute the original HOX function.

PMID- 14641328
TI  - Beta-catenin/Tcf activation partially mimics the transforming activity of Wnt-1
      in Rat-1 fibroblasts.
AB  - We have previously demonstrated that Wnt-1 induction of cytosolic beta-catenin
      and Tcf/Lef transcriptional activation correlate with enhanced proliferation,
      survival, and post-confluent growth in Rat-1 fibroblasts. To examine whether beta
      catenin mediates the biological responses to Wnt-1 in this context, we
      characterized Rat-1 clonal cell lines expressing different levels of a mutant,
      stabilized beta-catenin (beta-cateninS37A). Clonal lines exhibit elevated
      cytosolic and nuclear beta-cateninS37A and Tcf transcriptional activation,
      comparable to that elicited by Wnt-1 expression. However, expression of beta
      cateninS37A does not promote growth of Rat-1 cells in serum-free conditions and
      only partially promotes growth post-confluence, when compared to that induced by
      Wnt-1 expression. As ectopic expression of beta-cateninS37A only partially mimics
      Wnt-1 effects on Rat-1 cells, we conclude that Wnt-1 signaling elicits
      biochemical events that act in addition to beta-catenin/Tcf signaling to promote
      cell growth.

PMID- 14641329
TI  - Distinct expression patterns of splicing isoforms of mNumb in the endocrine
      lineage of developing pancreas.
AB  - The pancreas is composed of three tissues: endocrine, exocrine, and duct. The
      endocrine/exocrine lineages diverge from the ductal lineage before E12.5 in mice,
      and then further separate into endocrine and exocrine precursors. These processes
      are regulated by differential activation of Notch1-mediated signaling, which is
      required to repress the expression of the pro-endocrine gene neurogenin3 (ngn3)
      in the exocrine lineage. Mammalian Numb (mNumb) is an ortholog of Drosophila Numb
      (dNumb), which is likely to be an intracellular inhibitor of Notch signaling, and
      has four splicing isoforms: PTBS-PRRS, PTBL-PRRS, PTBS-PRRL, and PTBL-PRRL. Here
      we developed an anti-PRRL antibody, which recognizes only the PRRL forms of
      mNumb. We then performed immunohistochemical analyses using anti-PRRL together
      with anti-pan Numb, which recognizes all the isoforms of mNumb, antibodies that
      determine the spatio-temporal expression pattern of mNumb in the mouse fetal
      pancreas. mNumb PRRS and PRRL were first expressed in identical cells in the
      early stage of pancreatic development (i.e., E10.5), but gradually became biased.
      At the stage of endocrine and exocrine divergence, mNumb PRRS continued to be
      expressed in endocrine lineage cells, whereas PRRL was down-regulated during
      endocrine differentiation. Even after the endocrine/exocrine divergence, notch1
      expression was sustained in endocrine lineage, where ngn3 was expressed. These
      results agree with the notion that mNumb PRRS has an inhibitory effect on Notch
      signaling, indicating its potential roles in the differentiation of pancreatic
      endocrine lineage. In addition, islet cells, which are produced from ductal
      tissue, were immunostained by the anti-panNb antibody. Our present results will
      contribute to the understanding of the mechanisms of islet development from
      ductal tissue.

PMID- 14641330
TI  - Nasal capsular cartilage is required for rat transpalatal suture morphogenesis.
AB  - In the cranial vault, suture morphogenesis occurs when the growing cranial bones
      approximate and overlap or abut one another. Patency of developing sutures is
      regulated by the underlying dura mater. Once cranial sutures form, bone growth
      proceeds from the sutures in response to growth signals from the rapidly
      expanding neurocranium. Facial sutures do not develop in contact with the dura
      mater. It was therefore hypothesized that facial suture morphogenesis and bone
      growth from facial sutures are regulated by tissues with an equivalent role to
      the dura mater. The present study was designed to test this hypothesis by
      characterizing the morphology and growth factor expression in developing
      transpalatal (TP) sutures and their surrounding tissues, and then assessing the
      role of the overlying nasal capsular (NC) cartilages in maintaining suture
      patency. TP sutures develop as overlapping sutures, similar to cranial coronal
      sutures, and expression of Tgf-betas in TP sutures was similar to their
      distribution in cranial coronal sutures. To establish whether NC cartilages play
      a role in regulating TP suture morphogenesis, fetal rat TP sutures were cultured
      with associated attached NC cartilages or with NC cartilages removed. Sutures
      cultured for upward of 5 days with intact NC cartilages remained patent and
      maintained their cellular and fibrous components. However, in the absence of NC
      cartilages, the cellular nature of the sutures was not maintained and they became
      progressively acellular, with bony bridging across the suture. This finding is
      similar to that for cranial vault sutures cultured in the absence of dura mater,
      indicating that NC cartilages play an equivalent role to dura mater in
      maintaining the patency of developing sutures. These studies indicate that tissue
      interactions likely regulate morphogenesis of all cranial and facial sutures.

PMID- 14641331
TI  - Regulation of heart size in Xenopus laevis.
AB  - The region with the potential to form the heart has traditionally been called the
      heart field. This region can be approximated by, but is not identical to, the
      expression domain of the early cardiac gene Nkx2.5. The region expressing Nkx2.5
      does not change in size, although there are major shape changes and a subdivision
      of the region into non-myogenic and myogenic lineages. Using a variety of embryo
      manipulations, we have sought to determine whether cellular interactions could
      change the size of the initial Nkx2.5-expressing region and thus change the size
      of the heart. We have shown that if the heart is isolated from the dorsal half of
      the embryo, the volume of tissue expressing myocardial differentiation markers
      increases, indicating that signals restricting the size of the heart come from
      the dorsal side. Despite the change in myocardial volume, the non-myogenic heart
      lineages are still present. The ability of dorsal tissues to restrict the size of
      the heart is further demonstrated by fusing two Xenopus embryos shortly after
      gastrulation, generating twinned embryos where the heart of one embryo would
      develop adjacent to different tissues of the second embryo. The final size of the
      differentiated heart was markedly reduced if it developed in close proximity to
      the dorso-anterior surface of the head but not if it developed adjacent to the
      flank or belly. In all cases, the manipulations that restricted the size of the
      myocardium also restricted the expression of Nkx2.5 and GATA-4, both key
      regulatory genes in the cardiogenic pathway. These results provide evidence for a
      model in which signals from dorso-anterior tissues restrict the size of the heart
      after gastrulation but before neural fold closure.

PMID- 14641332
TI  - No smoking gun: findings from a national survey of office-based cosmetic surgery
      adverse event reporting.
AB  - BACKGROUND: Because of recent press reports of adverse outcomes, office-based
      cosmetic surgery has come under intense scrutiny and associated legislative
      regulatory action. OBJECTIVE: To assess the safety of office-based cosmetic
      surgery through a national survey of state agencies that collect information on
      adverse patient outcomes. METHODS: Medical boards or other responsible
      authorities were contacted in 48 states to obtain records on adverse outcomes
      from cosmetic surgery procedures performed in an office-based setting. RESULTS:
      Five states were able to provide complete information regarding 13 cases of
      adverse outcomes that resulted from office-based cosmetic surgery procedures.
      Thirteen states had incomplete information or were unable to provide information.
      The remaining states reported no adverse outcomes. Information collected by state
      agencies varies greatly and is inadequate to define the safety of office-based
      cosmetic surgery practice. CONCLUSIONS: The need to regulate physician office
      surgery on the basis of hospital privileges and office certification is not
      supported by current data. Mandatory reporting of adverse outcomes from office
      based surgery is warranted to identify modifiable risk factors and to reduce the
      risk of adverse outcomes.

PMID- 14641333
TI  - Skin cancer in an atomic veteran: cause or coincidence?
AB  - BACKGROUND: Some military personnel who were exposed to ionizing radiation during
      atomic weapons tests subsequently developed skin cancer, but the cause-effect
      relationship is unclear. OBJECTIVE: To explore the possible relationship between
      exposure to atomic tests and the development of skin cancer. METHODS: We reviewed
      available literature regarding the effects of radiation on the skin and the case
      history of a patient in whom more than 300 basal cell carcinomas developed over a
      30-year period after exposure to radiation during atomic testing. RESULTS AND
      CONCLUSIONS: Ionizing radiation can cause skin cancer, usually basal cell
      carcinoma. In some veterans of atomic testing, skin cancer may have been
      initiated by ionizing radiation and promoted by ultraviolet radiation. We
      conclude that exposure to ionizing radiation during atomic weapons testing
      contributed to the excessive number and location of basal cell carcinomas in our
      patient.

PMID- 14641334
TI  - Axillary basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) rarely occurs in the axilla. Only 18 cases
      have been reported in the world literature. OBJECTIVES: To report our
      institution's 11-year experience with axillary BCC. METHODS: A review of patient
      charts and biopsy specimens is given. RESULTS: We report 14 patients with 15
      axillary BCCs. The average patient age was 65.6. The average lesion size was 10.8
      mm. Nine patients had a personal history of skin cancer at sun-exposed sites. One
      patient had basal cell nevus syndrome. A history of ionizing radiation and severe
      sunburn involving the axilla was each seen in separate patients. No other
      predisposing factors for developing BCC were identified, such as immune
      suppression or a history of other malignancies. Histologic subtypes of all tumors
      were considered less aggressive, and only one tumor recurred. CONCLUSIONS:
      Axillary BCC is rare. Factors other than ultraviolet radiation likely contribute
      to the development of BCC, especially at sun-protected sites. Performing a
      periodic and complete cutaneous examination that includes sun-protected sites is
      important, especially in patients who have a history of skin cancer.

PMID- 14641335
TI  - Mohs tissue mapping and processing: a survey study.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is the most reliable, conservative,
      and tissue-sparing approach to the management of cutaneous malignancies. The
      concept of MMS is simple, but its technique, which involves a series of
      suboperations, is complex. OBJECTIVE: To define which techniques of Mohs tissue
      mapping and processing are presently employed by members of the American College
      of Mohs Micrographic Surgery and Cutaneous Oncology. METHODS: Five hundred eighty
      surveys of eight questions regarding different techniques used in Mohs tissue
      mapping and processing were mailed out to Mohs micrographic surgeons registered
      with the American College of Mohs Micrographic Surgery and Cutaneous Oncology. A
      total of 310 responses (53%) were collected between October and December 2002.
      The results were tabulated and analyzed. RESULTS: Most Mohs micrographic surgeons
      personally prepare the map of the tissue in relationship to the patient (66.5%).
      A hand-drawn picture with standard orientations is most frequently used to map
      and orient a tissue specimen (69.4%). Histotechnicians usually prepare the tissue
      specimen for cryostat processing (63.5%). A heat extractor and/or tissue cuts or
      "slits" are the preferred methods used to flatten tissue by 52.9% of respondents.
      Hematoxylin and eosin is the stain that is most commonly used (82.6%).
      Approximately 50% of Mohs micrographic surgeons cut the excised specimen from the
      first stage into two separate pieces. Each tissue piece is then commonly
      processed into three to six representative serial sections per glass slide
      (68.1%). These sections are most commonly cut at 5 to 6 microm (53.9%) and less
      frequently at 4 microm (21.9%). CONCLUSION: There is variability in mapping and
      processing techniques employed Mohs micrographic surgeons and their
      histotechnicians. As long as the integrity of each step of Mohs tissue mapping
      and processing is preserved, the high cure rate of the technique should be
      maintained.

PMID- 14641336
TI  - Delayed full-thickness skin grafts revisited.
AB  - BACKGROUND: There are many options for the management of surgical defects after
      Mohs micrographic surgery (MMS). For patients with complex defects who are not
      candidates for immediate grafting or who lack appropriate donor skin for a flap
      or who do not desire to undergo a major flap procedure, delayed full-thickness
      skin grafting (FTSG) may be an option. OBJECTIVE: To determine the role and
      usefulness of delayed FTSG in the management of Mohs surgical defects. METHODS:
      The records of 70 patients, seen over a 5-year period, who had their Mohs
      surgical defects repaired with a FTSG or who were scheduled for a delayed FTSG,
      were reviewed, along with their accompanying photographs (when available). The
      outcome of immediate and delayed FTSG was compared in terms of (1) graft loss,
      (2) epidermal sloughing, (3) thickening and/or irregularity, (4) contour
      correction, (5) hypopigmentation/hyperpigmentation, (6) persistent erythema, and
      (7) need for surgical revision. RESULTS: Twenty-seven patients underwent
      immediate FTSG, and 20 patients underwent delayed FTSG on an average 3.6 weeks
      after Mohs surgery. Twenty patients, originally scheduled for a delayed FTSG,
      were allowed to heal by second intention, with a very satisfactory cosmetic
      result in most instances. When patients undergoing immediate FTSG were compared
      with those undergoing delayed FTSG, there was essentially no difference in the
      two groups, as judged by the parameters cited previously here. CONCLUSION:
      Delayed skin grafting is often a viable option for patients undergoing Mohs
      surgery who are not candidates for immediate FTSG or who lack appropriate donor
      skin for a flap or who do not desire a major flap repair. It also has the added
      advantage in that as these patients are monitored in preparation for delayed
      grafting, it quite often becomes obvious that a significant proportion (more than
      50%) can be allowed to heal by second intention with a satisfactory cosmetic
      result.

PMID- 14641337
TI  - A modified running subcuticular suturing technique for the closure of defects
      after Mohs micrographic surgery.
AB  - BACKGROUND: The running subcuticular suturing technique is useful for the closure
      of surgical defects with minimal tension. OBJECTIVE: To determine the safety and
      efficacy of a modified running subcuticular suturing technique for the closure of
      facial wounds produced by Mohs micrographic surgery. METHODS: Five patients
      between the ages of 58 and 92 years, each with one Mohs defect on the face, were
      studied. One half of each defect was repaired with simple interrupted sutures,
      and the other half was repaired using the modified running subcuticular
      technique. RESULTS: There were no major differences in cosmetic outcome of the
      surgical sites at suture removal and at 1-week and 3-month follow-up
      examinations. No surgical complications occurred in any of the patients studied.
      CONCLUSION: We demonstrate that the modified running subcuticular suturing
      technique may be a safe and effective alternative for the primary, layered
      closure of defects from Mohs micrographic surgery.

PMID- 14641338
TI  - A training model for cutaneous surgery.
AB  - BACKGROUND: Training models are necessary for development of many skills in
      medical education. OBJECTIVE: To develop a training model for improvement of
      simple surgical procedure skills. METHODS: A convex, rectangular, smooth-surfaced
      wooden plate covered by first cotton material and then polyethylene stretch film
      was used. Skins of rats that had been used previously for experimental studies
      were attached on the wooden plate. In order to see efficacy of our model, we
      decided to use it in a cutaneous surgery workshop. Theoretical and practical
      information about surgical sutures, punch biopsy, excisional biopsy, rotational
      flap, and Z-plasty procedures was given to the participant physicians. Surgical
      skills of participants were scored before and after the practical part of
      workshop. RESULTS: Thirty-three physicians were enrolled voluntarily to the
      workshop. All participants showed statistically significant increase in scores (P
      < 0.05). CONCLUSION: The similarity to human skin and the easy setup make this
      training model an ideal teaching tool to improve the skills of physicians for
      simple cutaneous surgery.

PMID- 14641339
TI  - Longitudinal nail biopsy: utility in 20-nail dystrophy.
AB  - BACKGROUND: Twenty-nail dystrophy (TND) is an inflammatory disorder of the nail
      unit. It is frequently encountered in childhood and is believed to be a common
      clinical manifestation of several nail pathologies. Varying associations and
      histopathologic features have been reported previously. OBJECTIVES: To evaluate
      the clinical and histopathologic profile of TND and the utility of longitudinal
      nail biopsy (LNB) for the same. METHODS: Thirty-two consecutive patients with TND
      were screened clinically. The histopathologic features of skin and longitudinal
      nail biopsies were also evaluated. The efficacy of nail unit biopsy was thereby
      assessed. RESULTS: Young males in the 10- to 20-year-old age group were most
      commonly affected (52%). Alopecia areata was the most commonly associated
      dermatosis (22%). LNB revealed a specific diagnosis of either psoriasis or lichen
      planus in 52% of the cases, whereas the rest showed nonspecific histologic
      changes (spongiotic trachyonychia). Scarring was a major risk associated with
      LNB, as evident in 28% of the patients studied. CONCLUSIONS: These data reveal
      the clinical profile and common associations of TND. They also confirm the
      diagnostic utility of nail biopsy in TND patients and advocate this procedure in
      cases in which the clinical diagnosis is otherwise obscure. However, it cannot be
      recommended in the routine evaluation of patients with a relatively benign
      disorder such as TND. Furthermore, nail biopsy is proven to be a relatively
      simple and useful procedure.

PMID- 14641340
TI  - Androgenetic alopecia: combining medical and surgical treatments.
AB  - BACKGROUND: Medical treatment or surgical reconstruction is used separately to
      treat androgenetic alopecia. Two drug molecules (5% minoxidil solution and oral
      finasteride 1 mg) have proven efficacy to stabilize hair loss and promote hair
      regrowth. Microtransplant of one to three hair follicular unit grafts can provide
      a definitive hair restoration with a natural appearance. OBJECTIVES: Aesthetic
      results can be optimized with a combination of drugs and transplantation of
      follicular unit grafts. The Dynamic Multifactorial Classification is used to
      select suitable candidates for this combined approach and also to assess follow
      up results. RESULTS: Dynamic Multifactorial Classification assists the evaluation
      of the natural history of androgenetic alopecia evolution and also the effects of
      treatment. Regression of male androgenetic alopecia from Hamilton type V to type
      III can be achieved by combining drugs with hair grafts. CONCLUSION: Improvement
      of investigative methods and especially the Dynamic Multifactorial Classification
      makes it easier for a patient to follow the results of treatment adapted to their
      case.

PMID- 14641341
TI  - Endovenous laser surgery of the incompetent greater saphenous vein with a 980-nm
      diode laser.
AB  - BACKGROUND: In recent years, the minimal endoluminal invasive alternatives
      against surgical ligation and stripping for the treatment of incompetent greater
      saphenous vein (GSV) have been explored. Endovenous laser surgery is one of these
      endoluminal alternatives, and its clinical results are being reported at up to 3
      years. OBJECTIVE: To evaluate the safety and efficacy of a 980-nm diode laser for
      the elimination of the incompetent GSV. METHOD: Fifteen limbs in 12 patients with
      incompetent GSV were treated via an endovenous route with a 980-nm laser under
      local anesthesia in an outpatient setting. The effects were evaluated clinically
      along with duplex ultrasound at 1, 4, and 12 weeks after the treatment to
      determine efficacy and possible complications. RESULTS: Complete occlusion and
      retraction of treated GSV in all patients were observed during the 12 weeks of
      the postoperative period. There have been no significant complications to be
      concerned. CONCLUSION: The endovenous 980-nm diode laser surgery is a relatively
      simple, safe, office-based procedure that is expected to promise favorable
      results while a long-term follow-up is awaited.

PMID- 14641342
TI  - Extra-fine insulin syringe needle: an excellent instrument for the evacuation of
      subungual hematoma.
AB  - BACKGROUND: The most commonly used treatment method for subungual hematoma is
      nail trephining, which has some disadvantages. OBJECTIVE: To introduce a very
      simple and well-tolerated treatment technique for this common problem. METHODS:
      We used an extra-fine, 29-gauge insulin syringe for evacuation. We inserted the
      needle very close to the nail plate to minimize pain. We drained the blood from
      the hyponychium under the nail plate using this extra-fine needle. RESULTS: The
      technique described herein is very fast and simple, and the patients tolerate it
      well. It is particularly successful for the treatment of smaller subungual
      hematomas of the second, third, and fourth toenails, in which the trephining is
      harder. CONCLUSION: For these reasons, we suggest this technique as a practical
      alternative to the traditional nail trephining methods.

PMID- 14641343
TI  - Liposuction using dilute local anesthesia.

PMID- 14641344
TI  - Counterpoint.

PMID- 14641345
TI  - Squamous cell carcinoma arising in a Leishmania scar.
AB  - BACKGROUND: The appearance of squamous cell carcinoma (SCC) in chronic scar
      lesions of various etiologies has been reported. Here we present a case of SCC
      developing in a Leishmania scar after 59 years. OBSERVATIONS: An Iranian female
      presented with a SCC that arose when she was 3 years of age in a scar that was
      secondary to cutaneous Leishmania. CONCLUSIONS: SCC should be included as a rare
      but late sequela of cutaneous Leishmania.

PMID- 14641346
TI  - Treatment of squamous cell carcinoma with intralesional 5-Fluorouracil.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) has been used topically and intralesionally to
      treat lesions related to squamous cell carcinoma (SCC) such as actinic keratosis,
      Bowen's disease, and keratoacanthoma. OBJECTIVE: We sought to determine whether
      intralesional 5-FU might be effective in treating a patient with SCC. METHODS: A
      patient with SCC at the junction of the right alar crease and right nasolabial
      fold was treated with eight weekly injections of 5-FU, with doses ranging from
      0.8 to 2.4 mL. RESULTS: A repeat biopsy after the eighth treatment showed total
      clearance of the cancer, and the patient has remained free of recurrence during a
      5-month follow-up period. CONCLUSION: This modality may provide patients with SCC
      in cosmetically important locations or in areas that require complex surgery the
      advantage of a nonsurgical cure.

PMID- 14641347
TI  - Atypical cellular neurothekeoma.
AB  - BACKGROUND: Neurothekeoma is a distinctive neoplasm that in the past was often
      lumped into the broad category of benign peripheral nerve sheath tumors. Atypical
      cellular neurothekeoma is a rare variant of this neoplasm. This atypical variant
      is characterized by features that can include the following: large sizes (up to 6
      cm), deep penetration extending into skeletal muscle and/or subcutaneous fat,
      diffusely infiltrative borders, vascular invasion, high mitotic rate, and marked
      cytologic pleomorphism. METHODS: In this report, we describe the clinical,
      histopathologic, and immunohistochemical features of a case of atypical cellular
      neurothekeoma in a 34-year-old woman. RESULTS: This neoplasm demonstrated both
      the cellular subtype and intermediate subtype. In the cellular area, cells
      demonstrated rounded or ovoid nucleus with abundant cytoplasm. Mitotic activity
      ranged from 8 to 12 per 10 high-powered fields, and few individual cell necroses
      were present. In the intermediate area, cells were arranged as smaller nests with
      admixed abundant mucin. Mitotic activity ranged from 1 to 2 per 10 high-powered
      fields. These cells were negative for S100, epithelial membrane antigen, and
      smooth muscle actin. CONCLUSION: Dermatologists should be aware of the features
      of atypical cellular neurothekeoma. Although the atypical features raise concern
      about the malignant potential of this lesion, previous cases show that complete
      surgical excision of these lesions is curative.

PMID- 14641348
TI  - Cryptococcal necrotizing fasciitis with multiple sites of involvement in the
      lower extremities.
AB  - BACKGROUND: Cryptococcal necrotizing fasciitis that is localized to the lower
      extremities is very rare. OBJECTIVE: We describe a case of a renal transplant
      recipient who presented with necrotizing fasciitis of the legs caused by
      Cryptococcus neoformans, a fungus that is rarely associated with this disease.
      METHODS: This is a case report with literature review. RESULTS: The patient was
      hospitalized, and the site of infection was debrided to the level of the
      periosteum. Cultures and histopathologic examination of biopsy material revealed
      an invasive deep-seated infection with a fungal organism that was consistent with
      C. neoformans. After 21 days on parenteral amphotericin B (Ambisome; Er-Kim
      Pharmaceuticals) treatment, the patient was switched to oral itraconazole
      (Itraspor; Janssen-Cilag Pharmaceuticals) 200 mg/day. He was discharged after 30
      days of hospitalization with his wounds completely healed. He continued on oral
      fluconazole for a total course of 6 weeks. CONCLUSION: Systemic fungal infections
      continue to be an important cause of morbidity and mortality in transplant
      recipients. The insidious nature and atypical manifestations of these infections
      often delay diagnosis and therapy. In immunosuppressed patients, persistent fever
      that does not respond to antibacterial therapy should alert the physician to the
      possibility of fungal infection.

PMID- 14641349
TI  - Treatment of Dowling-Degos disease with Er:YAG-laser: results after 2.5 years.

PMID- 14641350
TI  - Re.: The anatomic sites of postliposuction fat deposition.

PMID- 14641351
TI  - Bilateral rhombic flaps for defects on the nasal dorsum and supra-tip.

PMID- 14641352
TI  - Prediction of irritancy in the human skin irritancy model and occupational
      setting.
AB  - It is of great importance to find ways to lower the incidence of chronic irritant
      contact dermatitis. In this process, it is crucial to have insight in the factors
      that can predict irritancy. This review offers a survey of recent findings in the
      field of skin irritancy testing, discussed in the context of renowned, older
      work. Extrinsic and intrinsic factors that may determine the outcome of irritancy
      testing in the human skin model are considered. In recent decades, there has been
      increasing interest in factors influencing the development of occupational
      dermatitis by means of prospective cohort studies. This promising new area of
      investigation is discussed separately.

PMID- 14641353
TI  - Nordic Occupational Skin Questionnaire (NOSQ-2002): a new tool for surveying
      occupational skin diseases and exposure.
AB  - Occupational skin diseases are among the most frequent work-related diseases in
      industrialized countries. Good occupational skin disease statistics exist in few
      countries. Questionnaire studies are needed to get more data on the epidemiology
      of occupational skin diseases. The Nordic Occupational Skin Questionnaire Group
      has developed a new questionnaire tool - Nordic Occupational Skin Questionnaire
      (NOSQ-2002) - for surveys on work-related skin disease and exposures to
      environmental factors. The 2 NOSQ-2002 questionnaires have been compiled by using
      existing questionnaires and experience. NOSQ-2002/SHORT is a ready-to-use 4-page
      questionnaire for screening and monitoring occupational skin diseases, e.g. in a
      population or workplace. All the questions in the short questionnaire (NOSQ
      2002/SHORT) are included in the long version, NOSQ-2002/LONG, which contains a
      pool of questions to be chosen according to research needs and tailored to
      specific populations. The NOSQ-2002 report includes, in addition to the
      questionnaires, a comprehensive manual for researchers on planning and conducting
      a questionnaire survey on hand eczema and relevant exposures. NOSQ-2002
      questionnaires have been compiled in English and translated into Danish, Swedish,
      Finnish and Icelandic. The use of NOSQ-2002 will benefit research on occupational
      skin diseases by providing more standardized data, which can be compared between
      studies and countries.

PMID- 14641354
TI  - Angioedema and dysphagia caused by contact allergy to inhaled budesonide.
AB  - Inhaled corticosteroids may cause various adverse effects ranging from irritation
      to severe anaphylactic reactions and systemic contact dermatitis. We report a 43
      year-old woman who developed sore throat, swelling of the lips and oral cavity
      and dysphagia, 2 weeks after the use of budesonide spray (Budefat) for treatment
      of bronchial asthma. The symptoms occurred with a delay of 3-4 h after the
      treatment x2 daily. There were no immediate reactions on prick and intracutaneous
      testing with the commercial product used by the patient. However, marked pruritic
      infiltration developed within 24 h, progressing to coalescing eczematous lesions
      over the following 2 days. In addition, severe oedema of the right upper eyelid
      was observed. On patch testing, budesonide was strongly positive at day 2 and 3
      in a concentration ranging from 1% to 10 p.p.m. (in petrolatum). Other
      corticosteroids of group A, B, C and D were completely negative. Repeated open
      application tests with amcinonide and triamcinolone acetonide cream on the
      ventral aspect of the upper arm were negative. Bronchial exposure to alternative
      sprays containing beclomethasone dipropionate (group D), fluticasone-17-
      propionate (D) and dexamethasone-21-isonicotinate (C) was well tolerated. In
      conclusion, this case is instructive, because the symptoms which developed after
      a short period of corticosteroid inhalation suggested a type I allergy. Testing
      proved a severe type IV contact allergy restricted to budesonide (group B),
      without cross-reactions to major corticosteroids of other groups.

PMID- 14641355
TI  - Efficacy of dexpanthenol in skin protection against irritation: a double-blind,
      placebo-controlled study.
AB  - Dexpanthenol is popular in treating various dermatoses and in skin care, but few
      controlled clinical trials have been performed. We investigated the efficacy of
      dexpanthenol in skin protection against irritation in a randomized, prospective,
      double-blind, placebo-controlled study. 25 healthy volunteers (age 18-45 years)
      were treated for the inner aspect of both forearms with either Bepanthol
      Handbalsam containing 5% dexpanthenol or placebo x2 daily for 26 days. From day
      15-22, sodium lauryl sulfate (SLS) 2% was applied to these areas x2 daily.
      Documentation comprised sebumetry, corneometry, pH value and clinical appearance
      (photographs). 21 volunteers completed the study, 3 were excluded because of non
      compliance and 1 experienced a non-study-related, severe, adverse event. Only
      corneometry yielded a statistically significant difference, with decreased values
      following SLS challenge at the placebo sites (P < 0.05). Intraindividual
      comparisons showed superior results at the dexpanthenol-treated sites in 11 cases
      and in only 1 case at the placebo site. 6 volunteers experienced an irritant
      contact dermatitis, with more severe symptoms at the placebo site in 5 cases. In
      conclusion, dexpanthenol exhibits protective effects against skin irritation. The
      initiation of a study to evaluate the efficacy of dexpanthenol in preventing
      irritant occupational contact dermatitis under real workplace conditions is
      validated.

PMID- 14641356
TI  - Patch testing with components of water-based metalworking fluids.
AB  - Water-based metalworking fluids (MWFs) may cause both irritant and allergic
      contact dermatitis. Several well-known MWF allergens are available for patch
      testing, but considering the wide variety of possible components used in MWF, our
      diagnostic arsenal covers only a small part of potential allergens. We therefore
      selected 13 frequently used MWF components that might be sensitizers and had not
      yet been tested routinely. In 5 centres, 233 dermatitis patients with present or
      past occupational exposure to MWF were patch tested with this and other panels.
      Only 7 patients showed positive reactions to the study panel. Allergic reactions
      to the emulsifier diglycolamine [syn. 2-(2-aminoethoxy) ethanol] were seen in 5
      patients, and 1 patient each reacted positively to 2-amino-2-ethyl-1,3
      propanediol (AEPD) and methyldiethanolamine (MDEA). Clinical relevance of the
      reactions to diglycolamine was unequivocally proven by its presence in the MWF
      from the patients' workplace in 3 cases. Diglycolamine seems to be an important
      MWF allergen, independently from monoethanolamine and diethanolamine. A test
      concentration of 1% petrolatum (pet.) appears to be appropriate. The importance
      of AEPD and MDEA as MWF allergens still remains to be established. The lack of
      positive test reactions to the other MWF components tested may be due to their
      low-sensitizing potential or too low a patch test concentration being used.

PMID- 14641357
TI  - The irritation potential and reservoir effect of mild soaps.
AB  - Identification and reduction of external noxious factors is one key point in the
      strategy for the treatment and reduction of contact dermatitis. A wide variety of
      soaps on the market are claimed to be suitable for the use on sensitive skin due
      to their mildness. The aim of the present study was to illustrate possible
      differences in the irritation potential of 8 products and to investigate whether
      surfactant residues may form an irritant reservoir on the skin. The study was
      double-blind, randomized using healthy human volunteers. The inherent capacity of
      the products to induce irritation was determined using conventional patch test
      technique, whereas detection of potential surfactant residues on the skin was
      done using a methodology developed in the 1960s for detection of the
      corticosteroid reservoir in the stratum corneum. The method comprised the release
      of active substance from the stratum corneum reservoir by occlusion of the skin
      with an aluminium chamber, followed by evaluation of the biological response. In
      the present study, the soap-treated area was rinsed with water and then occluded.
      Instrumental measurements of the transepidermal water loss and superficial skin
      blood flow served as indicators of the injurious effects of the products. The
      results showed large differences in irritation potential between the products,
      and some of them demonstrated considerable damaging effect. Moreover, the study
      proved the presence of barrier-impairing residues on the skin after rinsing with
      water. Subclinical skin damage can make the skin vulnerable to further irritation
      and delay recovery of chronic irritant contact dermatitis.

PMID- 14641358
TI  - The association between ambient air conditions (temperature and absolute
      humidity), irritant sodium lauryl sulfate patch test reactions and patch test
      reactivity to standard allergens.
AB  - To support the decision as to whether erythematous patch test reactions to
      allergens are irritant or allergic, sodium lauryl sulfate (SLS, 0.5% in water)
      has been added to the standard patch tests since July 1996 in the Dortmund
      Department of Dermatology. Data on 1600 patients patch tested up until June 2001,
      as well as standardized data on ambient temperature and humidity obtained by the
      German Meteorological Service, were included in a logistic regression analysis
      taking age, sex and atopy as potential confounders into account. The pattern of
      association was heterogeneous: while doubtful reactions to nickel sulfate were
      significantly associated with dry/cold weather conditions, but not with SLS
      reactivity, the opposite was observed for lanolin alcohol, benzocaine and
      Myroxylon pereirae resin (balsam of Peru). Doubtful reactions to other allergens,
      namely formaldehyde, fragrance mix or p-phenylenediamine, were associated with
      both factors. For several other allergens of the standard series, no distinct,
      significant pattern could be discerned. In conclusion, meteorological conditions
      and SLS reactivity independently contribute information on individual
      irritability at the time of patch testing, and both should be considered.

PMID- 14641359
TI  - Hair dye allergy due to 3-nitro-p-hydroxyethyl-aminophenol.

PMID- 14641360
TI  - Allergic contact stomatitis from BIS-GMA and epoxy resins in dental bonding
      agents.

PMID- 14641361
TI  - Airborne photocontact dermatitis due to the insecticide phoxim.

PMID- 14641362
TI  - Contact dermatitis due to disodium ethylenediamine- tetraacetic acid in cosmetics
      and shampoo.

PMID- 14641363
TI  - Occupational contact dermatitis from chrysanthemum in a mortician.

PMID- 14641364
TI  - Decrease in nickel allergy in Germany and regulatory interventions.

PMID- 14641365
TI  - D-Limonene contact dermatitis from hand cleansers.

PMID- 14641366
TI  - Occupational contact urticaria from the solid-phase peptide synthesis coupling
      agents HATU and HBTU.

PMID- 14641368
TI  - Stethoscope earpiece-induced chemical depigmentation.

PMID- 14641367
TI  - Allergic contact dermatitis from the epoxy resin plasticizer diglycidyl ether of
      propylene glycol.

PMID- 14641369
TI  - Increased positive patch test reactivity to methyldibromo glutaronitrile.

PMID- 14641370
TI  - Contact vitiligo appearing after allergic contact dermatitis from aromatic
      reactive diluents in an epoxy resin system.

PMID- 14641371
TI  - Anaphylactic reaction elicited by patch testing with diclofenac.

PMID- 14641372
TI  - Recurrence of pemphigus foliaceus after allergic contact dermatitis from triple
      antibiotic ointment.

PMID- 14641373
TI  - Prediction of heart failure post myocardial infarction: comparison of ejection
      fraction, transmitral filling parameters, and the index of myocardial
      performance.
AB  - Following an acute myocardial infarction (MI), the development of congestive
      heart failure (CHF) has been associated with a reduced ejection fraction (EF),
      pseudonormal or restrictive diastolic filling, and an increased index of
      myocardial performance (IMP). STUDY OBJECTIVES: To determine the comparative
      predictive value of EF, transmitral filling parameters, and IMP for the
      development of CHF following a first MI. DESIGN AND SETTING: A retrospective
      analysis of consecutive echocardiographic and Doppler studies in patients
      admitted for their first acute MI from the years 1988 through 1992. We studied
      109 patients following their first MI with two-dimensional and Doppler within 24
      hours of MI. We divided patients into those who developed CHF within 15 days (43
      patients) and without CHF (66 patients). RESULTS: Patients who developed CHF had
      greater LV dilatation, lower EF (27.7%+/- 10.2% vs 45.6%+/- 13.2%, P < 0.001),
      higher E/A, shorter deceleration times (DCT; 157 +/- 69 msec vs 248 +/- 105 msec,
      P < 0.001), and increased IMP. Utilizing multiple logistic regression, EF
      (strongest predictor), DCT, and IMP were predictive of CHF. Nineteen patients in
      the no CHF group developed late CHF and had lower EFs (30.5%+/- 13.1% vs 50.5%+/-
      9.8%, P < 0.001), higher E/A and shorter DCTs (161 +/- 39 msec vs 283 +/- 103
      msec, P < 0.001). EF, DCT, and E/A were predictive of late CHF in patients
      without initial CHF. For patients admitted with a first MI, the EF, DCT, and to a
      lesser extent IMP predicted who would ultimately develop CHF. An EF < 40% or a
      DCT < 200 msec correctly predicted CHF in 60 of 62 patients. CONCLUSION: We
      conclude that the early and ultimate development of CHF following a first MI were
      associated with an moderately reduced EF < 40%, pseudonormal diastolic filling
      indices, and an increased IMP.

PMID- 14641374
TI  - Increased volume reduction of late left-atrial emptying for patients with
      pseudonormal mitral inflow: an analysis for differentiation between normal and
      pseudonormal mitral inflow.
AB  - This study was designed to define the role of left atrial (LA) wall motion during
      left ventricular (LV) diastolic phase for patients with pseudonormal mitral
      inflow. We perform the M-mode of posterior aortic, indicating LA, wall motion,
      and Doppler echocardiography following cardiac catheterization among 71 patients
      with a ratio of early (E) to late mitral flow (A) >1. The amplitude of total LA
      wall motion (TM), early LA rapid emptying (EM), and late LA emptying (AM) during
      the LV diastolic phase were all derived from M-mode analysis. Study patients were
      classified into two distinct groups according to the LV end-diastolic pressure
      (EDP): patients with a LVEDP value < 15 mmHg (n = 36, normal group), and patients
      with a LVEDP value > or = 15 mmHg (n = 35, pseudonormal group). Values of AM (4.7
      +/- 1.2 vs 5.5 +/- 1.2 mm) and AM/TM (0.43 +/- 0.07 vs 0.55 +/- 0.08) for the
      normal and pseudonormal groups, respectively, were significantly higher for the
      pseudonormal group, whereas EM (6.6 +/- 1.8 vs 4.8 +/- 1.4 mm), TM (11 +/- 3 vs
      10 +/- 2 mm), EM/AM (1.41 +/- 0.46 vs 0.91 +/- 0.28), EM/TM (0.58 +/- 0.10 vs
      0.48 +/- 0.07) were significantly higher for the normal group. Among these
      parameters, AM/TM correlated best with the time constant of LV isovolumic
      relaxation (r = 0.77, P < 0.001). Using an AM/TM ratio value of >0.5 as an
      indicator of LV diastolic function abnormality, the sensitivity, specificity,
      positive predictive values, and negative predictive values for the detection of
      pseudonormalization were 85%, 94%, 94%, and 87%, respectively. These findings
      suggest that the increased volume reduction of late LA emptying (AM/TM) during LV
      diastolic phase assessed by M-mode echocardiography is useful for evaluating
      pseudonormal mitral inflow.

PMID- 14641375
TI  - Effect of atrial septal mobility on transcatheter closure of interatrial
      communications.
AB  - BACKGROUND: Transcatheter techniques have evolved as alternatives to surgical
      closure of interatrial communications due to its less invasive nature and low
      morbidity. The technique may be limited by the inability to deploy the device
      and, thus, may be complicated by significant residual shunting. Mobile or
      redundant septal tissue has been implicated as a possible cause of unsuccessful
      closure. METHODS: To determine if atrial septal hypermobility precludes
      successful transcatheter device closure of interatrial communications, 69
      patients (mean age 46.4 +/- 17.5 years [male:female ratio 34:35]) with
      periprocedural transesophageal echocardiograms were reviewed. Septal excursion
      was defined as the maximal transit of the interatrial septum between either side
      of the plane connecting the superior and inferior attachment points. Unsuccessful
      closure was defined as subsequent cardiac surgery to close the defect, inability
      to deploy the device, recurrent attempts at closure, device malalignment,
      residual shunting greater than mild in degree on follow-up transthoracic study,
      and procedural complications. RESULTS: Reasons for closure were the following:
      embolic events (n = 48); platypnea/orthodeoxia (n = 15); atrial septal defect
      with right ventricular dilatation and paroxysmal atrial tachycardia (n = 2);
      atrial septal defect (n = 3); and prophylactic patent foramen ovale closure in a
      scuba diver (n = 1). Successful closure occurred in 76% of patients (n = 53).
      Compared with those patients with successful transcatheter closure, the mean
      septal excursion in patients with failed closure was 0.66 +/- 0.56 cm versus 0.76
      +/- 0.47 cm (P = not significant [NS]). CONCLUSION: Our results do not support
      the concern that exaggerated septal mobility compromises successful device
      closure of interatrial communications.

PMID- 14641376
TI  - Live three-dimensional echocardiography of the human fetus.
AB  - The purpose of this study was to investigate the feasibility of using a new three
      dimensional ultrasound system to perform fetal echocardiographic examination in
      real time. The device consisted of a Philips Sonos 7500 (Andover, MA) ultrasound
      system and a 4 MHz, 4X matrix transducer. The study was approved by the
      Institutional Review Board and was performed with the informed consent of the
      mother. The study population consisted of 12 singleton fetuses with gestational
      ages of 16-37 weeks. Of these, ten fetuses had normal cardiac anatomy, one had
      complete atrioventricular septal defect, and the other a thickened tricuspid
      valve. The system allowed comprehensive visualization of fetal cardiac anatomy
      and color Doppler flow unattainable by two-dimensional approaches. This
      preliminary investigation suggests that live three-dimensional fetal
      echocardiography could be a significant tool for prenatal diagnosis and
      assessment of congenital heart disease in the human fetus.

PMID- 14641377
TI  - Echocardiographic study of an intravenous leiomyoma: case report and review of
      the literature.
AB  - Intravenous leiomyoma is a rare tumor of smooth muscle with invasion to veined
      channels that affects women at reproductive age. The case of a 45-year-old woman
      is described, with history of oophorectomy and hysterectomy, in addition to
      abdominal surgery due to mesenteric tumor. Several months later, the patient
      developed syncope and dyspnea secondary to pulmonary embolism. Echocardiographic
      study reported a mass in right side of heart proceding from inferior vena cava.
      The patient underwent tumor surgical resection from left iliac vein and
      histologic study concluded intravascular leiomyomatosis.

PMID- 14641378
TI  - Review of methods for texture analysis of myocardium from echocardiographic
      images: a means of tissue characterization.
AB  - This review discusses the definition of texture and identifies its utility in
      echocardiography for characterization of tissue. Methods used for quantification
      of texture in echocardiography and other disciplines are discussed. Several
      methodologies, particularly the wavelet method of texture quantification, seem to
      be promising. Image texture analysis appears to be a fertile area for research in
      echocardiography.

PMID- 14641379
TI  - Aortoventricular fistula and abscess caused by vancomycin-resistant enterococcus
      in a hemodialysis patient.

PMID- 14641380
TI  - Descending aorta obstruction secondary to left subclavian stent: an uncommon
      source of emboli.

PMID- 14641381
TI  - Live three-dimensional echocardiographic assessment of mitral stenosis.
AB  - In the present study, we describe our experience in using live three-dimensional
      transthoracic echocardiography in the assessment of mitral stenosis.

PMID- 14641382
TI  - Live three-dimensional transthoracic echocardiographic assessment of coronary
      arteries.
AB  - In the present study, we are illustrating some of the adult patients in whom live
      three-dimensional transthoracic echocardiography was found useful in assessing
      proximal and mid-coronary arteries.

PMID- 14641383
TI  - Innovations in transesophageal echocardiographic imaging.
AB  - Over the last three decades, the continuing development of transesophageal
      echocardiography (TEE) has represented a major advance in our ability to
      visualize cardiovascular structures with ultrasound. TEE serves as a valuable
      complement to transthoracic echocardiography (TTE) by allowing: images to be
      obtained with less attenuation from structures such as the lung, muscle, bone,
      and soft tissue; high resolution visualization of structures not well seen by
      TTE, such as left atrial appendage, descending thoracic aorta, and prosthetic
      heart valves; and assessment of hemodynamics and flow disorders in greater
      detail. This article provides a brief overview of current as well as emerging
      clinical applications of transesophageal echocardiography.

PMID- 14641384
TI  - Esophageal Doppler: noninvasive cardiac output monitor.
AB  - In this article we describe the esophageal Doppler, a noninvasive, instantaneous
      cardiac output monitor. Its reliability has been demonstrated to be comparable to
      that of other current techniques used in the clinical arena to measure cardiac
      output. It helps guiding intravascular fluid resuscitation by quantifying the
      increase in flow in response to fluid challenges and by indicating the plateau of
      the patient's cardiac function curve. When the plateau has been reached, further
      fluid loading may result in congestion without improvement in systemic flow.
      Thus, measuring cardiac output is the only way to determine the upper limit for
      fluid intake. In addition, a strategy based on cardiac output optimization has
      proven beneficial in high-risk surgical patients.

PMID- 14641385
TI  - Current state of intraoperative echocardiography.
AB  - Intraoperative use of echocardiography is becoming more prevalent and is now
      considered an essential part of modern cardiac surgery. Echocardiography can be
      performed intraoperatively using transesophageal, epicardial or epiaortic, and
      substernal approaches. These techniques have a variety of applications in
      evaluating myocardial and valvular function, assessing aortic atheroma, and
      determining adequacy of various kinds of repair and reconstruction. Future
      applications will most likely involve more compact equipment, the implementation
      of epicardial and transesophageal real-time three-dimensional echocardiography,
      and better use of provocative methods of intraoperative testing.

PMID- 14641386
TI  - Use of intracardiac echocardiography to guide catheter closure of atrial
      communications.
AB  - Intracardiac echocardiography (ICE) is slowly replacing transesophageal
      echocardiography as the preferred imaging tool to guide device closure of atrial
      septal defects and patent foramen ovale. This article is a brief review of the
      literature related to ICE, the technical aspects ICE imaging, techniques for
      obtaining the standard views, and the future directions of this methodology.

PMID- 14641391
TI  - On bed baths and conceptual models of nursing.

PMID- 14641393
TI  - Minor illness education for parents of young children.
AB  - BACKGROUND: A number of previous studies on minor illness have concentrated on
      nurse-led clinics and the role of nurse practitioners. This study examines the
      effect of a minor illness education programme which aimed to increase parents'
      confidence and knowledge in managing childhood illnesses. AIM: The primary aim of
      this study was to evaluate the effectiveness of a home visit and booklet in
      providing education to parents about minor infant illnesses. DESIGN: A randomized
      controlled trial was conducted. The intervention involved a home visit to discuss
      parents' concerns and provide advice and information, and a booklet advising
      parents what to do and when to consult about infant illnesses. METHOD: A total of
      120 parents of 6 week old babies were identified over a 6 month period, using
      health visitors' caseloads, and randomized to an intervention group (60), that
      received a visit and a booklet, or a control group (60) that received standard
      care. Groups were compared on entry to the study and at 7 months, in terms of
      parental knowledge and confidence about childhood illnesses, the intended use of
      home care activities, intention to consult professionals and actual use of health
      services. Data were collected by self-completed questionnaire and case note
      review. FINDINGS: The educational intervention resulted in a reduction in visits
      to the child health clinic but had little effect on use of other services.
      Parents in the intervention group showed a general trend towards greater
      certainty about the home care options they would choose, and a reduction in
      intention to consult a doctor. However, they also indicated a feeling of reduced
      confidence and knowledge. CONCLUSION: The trial showed no effect on use of
      services but did demonstrate reduction in parents' intentions to consult a
      doctor, which appeared to be because of increased certainty about home care.
      However, it is of concern that they indicated feeling less confident and
      knowledgeable. It is not possible to clarify whether this represented anxiety
      that was constructive, enhancing decision-making or was destructive. Further work
      into the role of education in parental decision-making, anxiety levels and
      enhancement of confidence is required.

PMID- 14641394
TI  - Early detection and treatment of postnatal depression in primary care.
AB  - BACKGROUND: Postnatal depression has a relatively high incidence and gives rise
      to considerable morbidity. There is sound evidence supporting the use of the
      Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal
      depression. AIM: This paper reports on a project developed by two health visitors
      and a community mental health nurse working in the United Kingdom. The aim of the
      project was to improve the early detection and treatment of postnatal depression
      in the population of the general practice to which they were attached. METHOD:
      The health visitors screened for postnatal depression in the course of routine
      visits on four occasions during the first postpartum year. Women identified as
      likely to be suffering from postnatal depression were offered 'listening visits'
      as a first-line intervention, with referral on to the general practitioner and/or
      community mental health nurse if indicated. FINDINGS: Data collected over 3 years
      showed that the project succeeded in its aim of enhancing early detection and
      treatment of postnatal depression. These findings replicate those of other
      studies. The data also showed that a substantial number of women were identified
      for the first time as likely to be suffering from postnatal depression at 12
      months postpartum. Women screened for the first time at 12 months were at greater
      risk than those who had been screened earlier than this. CONCLUSIONS: Health
      visitors should screen for postnatal depression throughout the period of their
      contact with mothers, not solely in the immediate postnatal period. It is
      particularly important to screen women who, for whatever reason, were not
      screened when their child was younger. The knowledge and skills needed to use the
      Edinburgh Postnatal Depression Scale and provide first-line intervention and
      onward referral can be developed at practitioner level through close
      collaborative working.

PMID- 14641395
TI  - Adherence to diabetes control recommendations: impact of nurse telephone calls.
AB  - BACKGROUND: Type 2 diabetes mellitus is increasing in incidence and research has
      shown that normalization of blood glucose levels can moderate the risk of
      microvascular and neurological complications. AIM: The purpose of this study was
      to investigate the effect of nurse telephone calls on glycosylated haemoglobin
      (HbA1c) levels and adherence to diabetes control recommendations. METHODS: A
      randomized design with control and experimental groups being assessed pre- and
      post intervention was used to assess the effectiveness of nurse telephone calls.
      Twenty patients were randomly assigned to an intervention group and 16 to a
      control group. The goal of the intervention was to keep blood glucose
      concentrations close to the normal range (HbA1c < 7%). The intervention was
      applied to the intervention group for 12 weeks, and consisted of continued
      education and reinforcement of diet, exercise, medication adjustment
      recommendations, as well as frequent self-monitoring of blood glucose levels.
      Telephone intervention was performed twice per week for the first month and then
      weekly for the second and third month. Participants were requested to write self
      management logs including blood glucose levels, diet and an exercise diary. A
      dietitian analysed the diet diaries and participants were informed about their
      results by telephone or mail. All medication adjustments were communicated to
      participants' doctors. The HbA1c and diabetes adherence were measured before and
      after the intervention. RESULTS: Patients in the intervention group had a mean
      decrease of 1.2% in HbA1c levels and those in the control group had a mean
      increase of 0.6% in HbA1c levels. The intervention group had greater diet and
      blood glucose testing adherence than the control group. CONCLUSION: These
      findings indicate that a nurse telephone intervention can improve HbA1c, and diet
      and blood glucose testing adherence.

PMID- 14641396
TI  - 'Being positive': perceptions of patients with cancer and their nurses.
AB  - BACKGROUND: A review of popular literature reveals a constant message about the
      healing power of 'being positive'. While there are studies that have examined the
      link between psychosocial factors such as attitude and cancer survival, very
      little has been reported about the perceptions of patients and nurses on the
      meaning of 'being positive'. AIM: To explore the meaning of 'being positive' for
      patients undergoing cancer treatment and for nurses who care for them. METHODS: A
      qualitative, descriptive approach within the paradigm of constructivist inquiry
      was used. Semi-structured interviews were conducted with a self-selected
      convenience sample of 11 patients and eight nurses. The interviews addressed the
      following key concepts: definitions of 'being positive' and being negative; how
      these attributes are manifest in cancer patients; and factors influencing patient
      attitudes. FINDINGS: Patients defined 'being positive' as maintaining some sort
      of normality without letting cancer have a detrimental effect on daily living.
      Nurses identified hope, acceptance, fighting spirit and looking on the bright
      side as definitions of 'being positive'. Nurses and patients identified
      environment and support of family, friends and health professionals as factors
      that influence patient attitudes. Patients also identified other peoples'
      attitudes as important. CONCLUSIONS: 'Being positive' must be acknowledged as
      central to being able to cope with cancer and its treatment. The ability of
      nurses to care for patients with cancer and help them to remain positive will be
      improved if they develop a better understanding of the meaning of 'being
      positive' for patients, and how other peoples' attitudes affect their state of
      mind.

PMID- 14641397
TI  - Anxiety and well-being in older people after discharge from hospital.
AB  - BACKGROUND: A previous study using the State-Trait Anxiety Inventory (STAI) has
      documented a very high prevalence of anxiety symptoms among older inpatients. The
      STAI produced two main concepts on factor analysis -'Nervousness' and 'Well
      being'- and high scores on both caused the high overall score in these patients.
      AIM: To investigate how the scorings on the STAI evolve after discharge in older
      patients in order to understand better the reasons for their high scorings while
      in hospital. METHODS: Sixty-three patients who had been scored on the STAI during
      their stay in an elder care department were followed up at 1-3 and 12 months
      after discharge. Data were analysed by ancova for unbalanced designs. RESULTS:
      The mean STAI sum score increased significantly (3.5 points adjusted for the
      baseline scoring, age and gender, P < 0.001) from the first follow-up while in
      hospital to 1-3 months after discharge, with no significant change between the
      second and the last follow-up. This increase resulted primarily from a
      significant worsening of the score on 'well-being'. The score on 'nervousness'
      remained unchanged. Age did not influence the scores, while females scored
      higher. No interaction effects were observed, indicating that the evolvement of
      nervousness and anxiety after discharge is independent of gender and age. Item
      analysis showed that the worsening of the score on 'well-being' in these patients
      during the first 1-3 months after discharge was primarily caused by a lower score
      on the item 'I feel secure'. CONCLUSION: The study does not support the
      hypothesis that a high level of nervousness and lack of well-being among
      hospitalized older patients results from acute illness and hospitalization. The
      worsening in the score on well-being after discharge of such patients is
      primarily caused by low levels of feelings of security. This represents a
      challenge to nurses providing home-based care.

PMID- 14641398
TI  - Misrepresenting random sampling? A systematic review of research papers in the
      Journal of Advanced Nursing.
AB  - AIM: This paper discusses the theoretical limitations of the use of random
      sampling and probability theory in the production of a significance level (or P
      value) in nursing research. Potential alternatives, in the form of randomization
      tests, are proposed. BACKGROUND: Research papers in nursing, medicine and
      psychology frequently misrepresent their statistical findings, as the P-values
      reported assume random sampling. In this systematic review of studies published
      between January 1995 and June 2002 in the Journal of Advanced Nursing, 89 (68%)
      studies broke this assumption because they used convenience samples or entire
      populations. As a result, some of the findings may be questionable. DISCUSSION:
      The key ideas of random sampling and probability theory for statistical testing
      (for generating a P-value) are outlined. The result of a systematic review of
      research papers published in the Journal of Advanced Nursing is then presented,
      showing how frequently random sampling appears to have been misrepresented.
      Useful alternative techniques that might overcome these limitations are then
      discussed. REVIEW LIMITATIONS: This review is limited in scope because it is
      applied to one journal, and so the findings cannot be generalized to other
      nursing journals or to nursing research in general. However, it is possible that
      other nursing journals are also publishing research articles based on the
      misrepresentation of random sampling. The review is also limited because in
      several of the articles the sampling method was not completely clearly stated,
      and in this circumstance a judgment has been made as to the sampling method
      employed, based on the indications given by author(s). CONCLUSION: Quantitative
      researchers in nursing should be very careful that the statistical techniques
      they use are appropriate for the design and sampling methods of their studies. If
      the techniques they employ are not appropriate, they run the risk of
      misinterpreting findings by using inappropriate, unrepresentative and biased
      samples.

PMID- 14641399
TI  - Becoming a web-based learner: registered nurses' experiences.
AB  - AIMS: The purpose of the study was to describe Registered Nurses' experiences
      when taking a web-based course from either the workplace or home, and the impact
      of their learning on clinical practice. RATIONALE: Little is known about the web
      based learners' experience, particularly when courses are accessed from the
      nursing practice setting. Even less is known about whether nurses transfer their
      web-based learning to clinical practice. METHODS: A qualitative design employing
      focus group interviews was used. Participants included hospital and community
      nurses from three Canadian provinces and one territory. Data were collected at
      three points over a 6-month period and analysed using a thematic analysis
      process. These findings emanate from a larger study using survey method and focus
      group interviews. RESULTS: The focus group interviews captured the hurdles nurses
      faced during the first weeks when they struggled with technology, re-framed their
      views of teaching and adjusted to web-based learning from home and work. These
      first stressful weeks were followed by a period during which nurses developed
      relationships with the teacher and peers that enabled them to focus on learning
      and prevented attrition. Most nurses reported the web course was convenient and
      that they would be interested and comfortable using technology for learning and
      work purposes in the future. Six weeks after the course was completed, nurses
      articulated a number of ways the course had improved their practice. CONCLUSION:
      Initial weeks in a web-based course can be very challenging for novice Internet
      users, however, most nurses who completed the course reported a positive learning
      experience. Nurses, employers and educators should evaluate computer skills,
      computer access and the learning environment when preparing for web-based
      learning.

PMID- 14641400
TI  - Critical thinking disposition of Hong Kong Chinese and Australian nursing
      students.
AB  - BACKGROUND: Critical thinking is frequently cited as a desirable professional
      attribute and a highly valued educational outcome. Despite the abundance of
      literature on the subject, validation of the critical thinking construct in
      different cultural populations is under-researched. AIM: The purpose of this
      study was to compare the critical thinking dispositions of Hong Kong Chinese and
      Australian nursing students. DESIGN: A cross-sectional design was used with two
      groups of nursing students in two universities, one in Hong Kong and the other in
      Australia. Critical thinking disposition was measured using the California
      Critical Thinking Disposition Inventory (CCTDI). RESULTS: Significant differences
      were detected in critical thinking disposition between the two groups of students
      (P < 0.05), with the Hong Kong Chinese students failing to show a positive
      disposition toward critical thinking on the CCTDI total mean score, while the
      Australian students showed a positive disposition. Similarities and differences
      were also noted between the groups in CCTDI subscale mean scores. CONCLUSION: The
      findings contribute to knowledge of critical thinking by demonstrating
      differences and similarities between Hong Kong Chinese and Australian nursing
      students. The study raises questions about the effects of institutional,
      educational, professional and cultural factors on the disposition to think
      critically.

PMID- 14641401
TI  - Training needs of midwifery assistants.
AB  - BACKGROUND: Increasingly in the United Kingdom (UK) assistants are being
      introduced as part of the midwifery workforce. However, there appears to be
      little standardization in the qualifications and training provided. AIM: The aim
      of this study was to investigate what an educational programme for midwifery
      assistants should contain. RESEARCH METHODS: A total of 100 qualified midwives
      and 58 midwifery students were asked to complete a mailed questionnaire and
      subsequently 20 of these respondents were interviewed. RESULTS: Respondents
      identified three levels of competencies that midwifery assistants should possess.
      They also acknowledged that midwives required specific training in how best to
      supervise assistants. Respondents maintained that each assistant should have a
      clinically-based midwifery mentor and that rotation around different clinical
      areas should be included as part of a training programme. Furthermore, it was
      stressed that because midwives initiate, teach and supervise assistants, they
      should have a key role in planning training programmes and in the teaching and
      assessment processes. Nonetheless, it was accepted that such a role could divert
      the midwife from valuable contact time with the mother and baby, the opposite of
      what the introduction of assistants was intended to do. CONCLUSIONS: Before
      working in clinical areas midwifery assistants need practice-based training that
      focuses on skills development. Communications and interpersonal skills should be
      included in the training as should placement experience in a variety of clinical
      settings. Midwives have a role in providing this training, and in mentoring and
      supervising midwifery assistants, but it is accepted that this could add to their
      workloads. Developments of this kind need to be evaluated, especially in terms of
      the impact on direct care by midwives.

PMID- 14641404
TI  - The legendary beginning of the International Consultation on Interstitial
      Cystitis.

PMID- 14641403
TI  - Proceedings of the International Consultation on Interstitial Cystitis. March 28
      30, 2003. Kyoto, Japan.

PMID- 14641402
TI  - Review of research on the health of caregiving grandparents.
AB  - AIM: To provide a critical review of research literature on the health of
      grandparents raising grandchildren, and identify directions for future research.
      METHODS: Approaches used to access the research studies for this review included
      a comprehensive search using relevant electronic databases and a thorough
      examination of the references in each published study. FINDINGS: All studies but
      one were published after 1990. Samples consisted primarily of African-American
      and Caucasian grandmothers in the United States of America. Earlier studies
      tended to describe health and other related concepts while more recent studies
      began to examine relationships between concepts. Most of the studies had a cross
      sectional design and only one evaluated interventions. Inconsistencies in the
      results of these studies were prevalent. CONCLUSIONS: Evaluation studies,
      longitudinal designs, and more varied study samples including cross-cultural
      comparisons are needed to advance knowledge about grandparent caregivers' health.

PMID- 14641405
TI  - Interstitial cystitis, gynecologic pelvic pain, prostatitis, and their
      epidemiology.
AB  - AIM: To determine a uniform definition of interstitial cystitis (IC) and to
      develop a strategy on how to study its epidemiology. METHODS: Initially, the
      committee reviewed the literature regarding the definition of IC currently being
      used and information regarding its epidemiology. The committee held three 1-hour
      hearings and discussions on the opinions of invited IC specialists. The issues
      were presented and discussed. Consensus was sought when possible. The committee
      members met and summarized the gist of the three sessions. RESULTS: A consensus
      emerged as to what constitutes IC. Interstitial cystitis must have the elements
      of chronic pelvic pain and urinary frequency and/or urgency. It was also the
      recommendation that the term IC be retained followed by chronic pelvic pain
      syndrome represented by the acronym IC/CPPS. A strategy on the epidemiologic
      study of IC/CPPS was also recommended. CONCLUSIONS: A consensus from this
      workshop has emerged in terms of defining the component of IC, the preferred
      terminology, and the strategy to study its epidemiology.

PMID- 14641406
TI  - Research criteria versus clinical criteria for interstitial cystitis.
AB  - In March 2003 experts on interstitial cystitis (IC) from around the world met in
      Kyoto, Japan for a series of workshops intended to define areas of agreement and
      difference in the approach to this disease. This workshop explored the diagnostic
      criteria IC in the clinical and research settings. The NIDDK criteria are used
      almost universally for research but there is tremendous disparity in the clinics
      and no consensus at all as to the best practice in diagnosing IC for clinical
      purposes. Throughout the world many physicians use the NIDDK research criteria
      for clinical diagnosis; in some countries this is standard. Undoubtedly, this
      mandates under-diagnosis and denies treatment to many patients. Still, a majority
      feel that one diagnostic system is mandatory to promote clarity in communication.
      The group called for two initiatives to help advance this area of controversy:
      (1) a large-scale, prospective study critically examining the role of cystoscopy,
      bladder distention, and biopsy in the diagnosis of IC; (2) a concerted effort to
      develop a single evidence-based guideline or algorithm that would be flexible
      enough to meet the needs of clinicians, researchers, and patients.

PMID- 14641407
TI  - Pathology of interstitial cystitis.
AB  - In this workshop the participants were asked to consider the role of pathology in
      the diagnosis and management of interstitial cystitis (IC). Currently, the NIDDK
      definition of IC is made on clinical criteria; bladder biopsy is not required for
      the clinical work-up and histology is not used as a diagnostic criterion. The
      literature review described the most common pathological findings to be
      epithelial denudation or ulceration, mononuclear inflammation, edema, congestion,
      hemorrhage, and mast cell activation. These pathological changes were not
      universal or specific with 55% of IC subjects in one study having histology that
      was normal and indistinguishable from control subjects. Presentations were made
      which generally confirmed an association between abnormal pathology and more
      severe disease as determined by symptoms, cystoscopic capacity, and prognosis.
      During the workshop it was clear that whether or not a biopsy was performed
      depended on a number of factors, for example, country of origin, the research
      interest of the unit, and the desire to exclude malignancy on histological
      grounds. The consensus, which was not unanimous, was that bladder biopsy was a
      non-mandatory test in the clinical work-up of the patient with IC but that urine
      cytology should be performed. It was discussed that bladder biopsy be an optional
      test and particularly relevant when one was suspicious of other conditions and in
      IC research. It was hoped that bladder biopsy pathology will give clues to
      contributory pathogenic processes such as epithelial dysfunction and
      inflammation; and in the future, with the help of molecular biology, may help
      determine etiology.

PMID- 14641408
TI  - The place of cystoscopy and hydrodistension in the diagnosis of interstitial
      cystitis: a potpourri of opinions emanating from an International Consultation on
      IC in Kyoto, Japan, March 28-30, 2003.
AB  - The place of cystoscopy and hydrodistension in the diagnosis of interstitial
      cystitis (IC) was discussed by an international and Japanese panel of IC
      researchers. Cysto and hydrodistension (HD) has been traditionally regarded as
      pivotal to the diagnostic process. To assess the experts' opinions a
      questionnaire was circulated which revealed that 20 of the 31 responders regarded
      cysto and HD to remain as an important inclusion criterion in the diagnosis of IC
      (with 8 undecided and 3 against the inclusion). The questionnaire further
      demanded opinions about the specificity of the known IC changes at cysto and HD,
      correlation with the clinical picture, false positives, and methodology of the
      examination.

PMID- 14641409
TI  - Summary of the Urodynamics Workshops on IC Kyoto, Japan.

PMID- 14641410
TI  - Clinical symptoms scale for interstitial cystitis for diagnosis and for following
      the course of the disease.

PMID- 14641411
TI  - Current and future directions in diagnostic markers in interstitial cystitis.
AB  - Interstitial cystitis (IC) is a chronic bladder disorder of unknown etiology that
      is often diagnosed by symptom criteria with or without cystoscopic findings.
      Several potential diagnostic markers have recently been described that may
      facilitate diagnosis of this disorder. A summary of the literature and a
      discussion regarding these biomarkers is provided, along with a brief discussion
      of new biomarkers presented at the meeting.

PMID- 14641412
TI  - Future research needs for the definition/diagnosis of interstitial cystitis.
AB  - In Workshop 8 at the International Conference on Interstitial Cystitis (Kyoto
      March 2003, future research needs for the definition/diagnosis of interstitial
      cystitis (IC) were discussed by the participants. To structure discussions a
      study proposal was used. This workshop decided that research should focus on
      identifying and validating classification criteria for the diagnosis of IC. This
      might well be done in a (multi-centre) study with a control group of urge
      frequency patients without pain (OAB?). However, before doing so standards should
      be defined as on how to perform and interpret vaginal examination, urodynamic
      investigation, cystoscopy under anesthesia, potassium sensitivity test, and
      histopathology in these patients.

PMID- 14641413
TI  - Systemic aspects of interstitial cystitis, immunology and linkage with autoimmune
      disorders.
AB  - It is recognized that interstitial cystitis (IC) is often associated with a
      number of diseases such as allergies, irritable bowel syndrome, fibromyalgia,
      inflammatory bowel disease (Crohn's disease and ulcerative colitis), systemic
      lupus erythematosus, and Sjogren's syndrome. The prevalence of allergies in IC is
      reported to be between 40 and 80% of patients. The background of the association
      is not known and does not seem to be the result of a generalized allergic
      constitution. Some report that treatment of allergy sometimes has a beneficial
      effect on bladder symptoms. An increased expression of certain growth factors (PD
      ECGF, FGF, and VEGF) has been found in the bladder of IC patients. In addition,
      the expression of CD44 was significantly higher in ulcer type IC than in non
      ulcer type. In general, these growth factors are soluble and diffusible under
      normal conditions but proteoglycans such as CD44 could bind to these growth
      factors. This may promote the accumulation of growth factors at the sites of
      inflammation. CD44 expression in ulcer type IC could explain the prolonged and
      stronger expression of GAG-binding growth factors that promote inflammation. In
      the Rotterdam study, a strong association between IC and Sjogren's syndrome is
      recognized. In this study, 28% of IC patients have definite or probable Sjogren's
      syndrome. This association is much stronger than is generally recognized. This
      could be due to difficulties in diagnosing Sjogren's syndrome since a diagnosis
      usually requires a high index of suspicion.

PMID- 14641414
TI  - Interstitial cystitis and frequency-urgency syndrome (OAB syndrome).

PMID- 14641415
TI  - The basics behind bladder pain: a review of data on lower urinary tract
      sensations.
AB  - Interstitial cystitis is a syndrome consisting of frequency, urgency, and bladder
      pain that increases with bladder filling and improves temporarily after voiding.
      The exact cause or causes are not as yet fully understood. This leads to
      uncertainty in diagnosis and treatment. There is need for more knowledge, and to
      acquire this for more research. The fact that the condition causes pain, a
      pathologic stimulation of sensory fibres, makes understanding the basic sensory
      mechanisms in the lower urinary tract in normal and pathologic conditions
      mandatory. In this article we review the data on bladder sensation from the last
      25 years and the possible relation with painful bladder syndrome.

PMID- 14641416
TI  - Significance of complications of allergic diseases in young patients with
      interstitial cystitis.
AB  - BACKGROUND: It was found that about one-half of interstitial cystitis (IC)
      patients have complications of allergic diseases. However, significance of the
      complications have not been studied. PATIENTS AND METHODS: Thirty-four patients
      (age range 20 to 39 years old) meeting the diagnostic criteria of NIDDK
      established in 1987 were selected. Clinical allergic tests and significance of
      complications of allergic diseases were examined. RESULTS: Eighty-six percent of
      young patients had complications of allergic diseases. In two patients, IC was a
      part of generalized allergic diseases. In 25 patients, IC was suggested to have
      some association with allergy. Of these 25 patients, there were alternating
      symptoms or proportionally changing symptoms of allergy and IC in 15 patients,
      and the number of eosinophils increased in six patients. Seven IC patients were
      considered to have developed allergic diseases only by chance without apparent
      association. CONCLUSIONS: Complications of allergic diseases are frequent,
      particularly in young IC patients. The results suggest the involvement of allergy
      in about 80% of IC patients with complications of allergic diseases. In only 6%
      of patients, IC was a part of generalized allergic disease.

PMID- 14641417
TI  - International survey on interstitial cystitis.

PMID- 14641420
TI  - Chelating agents in root canal treatment: mode of action and indications for
      their use.
AB  - Chelating agents were introduced into endodontics as an aid for the preparation
      of narrow and calcified root canals in 1957 by Nygaard-Ostby. A liquid solution
      of ethylenediaminetetraacetic acid (EDTA) was thought to chemically soften the
      root canal dentine and dissolve the smear layer, as well as to increase dentine
      permeability. Although the efficacy of EDTA preparations in softening root
      dentine has been debated, chelator preparations have regained popularity
      recently. Almost all manufacturers of nickel-titanium instruments recommend their
      use as a lubricant during rotary root canal preparation. Additionally, a final
      irrigation of the root canal with 15-17% EDTA solutions to dissolve the smear
      layer is recommended in many textbooks. This paper reviews the relevant
      literature on chelating agents, presents an overview of the chemical and
      pharmacological properties of EDTA preparations and makes recommendations for
      their clinical use.

PMID- 14641421
TI  - Biocompatibility of resin-based materials used as pulp-capping agents.
AB  - AIM: To evaluate and compare the response of pulps of rats capped with resin
      modified glass-ionomer cement (RMGIC) or self-etching adhesive system.
      METHODOLOGY: Class I cavities were prepared on the occlusal surface of 54
      maxillary first molars of 27 rats. Pulp exposure was performed on the cavity
      floor. The following resin-based materials were applied as pulp-capping agents:
      G1, Clearfil Liner Bond 2V (CLB 2V; Kuraray Co., Japan); G2, Vitrebond (VIT;
      3M/ESPE, USA). In group 3 (control group), a calcium hydroxide/saline paste (CH;
      Labsynth, Brazil) was used. The cavities were restored with amalgam. After 7, 30
      and 60 days, the animals were sacrificed and the jaws were processed for
      microscopic evaluation. RESULTS: Despite the inflammatory response caused by the
      experimental and the control materials at 7 days, pulpal healing associated with
      calcified barrier formation was observed at 60 days following the pulp therapy.
      Both resin-based materials promoted a large zone of cell-rich fibrodentine matrix
      deposition on the pulp horn related to the pulp exposure site, which was larger
      to VIT than to CLB 2V specimens. Tertiary dentine underneath the fibrodentine
      matrix was deposited by a layer of elongated pulpal cells. The remaining pulpal
      tissue exhibited normal histological characteristics. In the control group,
      healing and dentine-bridge formation was observed at 30 days. Pulpal breakdown
      occurred only when bacterial infection occurred. CONCLUSION: Both experimental
      pulp-capping agents allowed pulpal healing characterized by cell-rich
      fibrodentine and tertiary dentine deposition as well as calcified barrier
      formation.

PMID- 14641422
TI  - Effect of nitric oxide synthase inhibitor (L-NAME) on substance P-induced
      vasodilatation in the dental pulp.
AB  - AIM: To investigate the vasodilator mechanisms of pulpal vessels, especially the
      involvement of nitric oxide (NO), during pulpal inflammation. METHODOLOGY: Eleven
      cats were prepared for intra-arterial administration of test agents through a
      lingual artery. The pulpal blood flow was measured by laser Doppler flowmetry
      from ipsilateral mandibular canine teeth. By using the NO synthase (NOS)
      inhibitor N(G)-nitro L-arginine methyl ester (L-NAME), the effects of L-NAME on
      various vasodilators, such as Substance P (SP)-, calcitonin-gene related peptide
      (CGRP)-, and papaverine-induced vasodilatation, were compared in vivo in 11
      feline dental pulps. RESULTS: L-NAME pretreatment potentiates SP-induced
      vasodilatation for a duration of approximately 5 h. The increase of pulpal blood
      flow ranged from 91.47 to 109.91%, which was significantly different from SP
      injection alone (48.79%, P < 0.05). Other vasodilators such as CGRP and
      papaverine did not respond to L-NAME pretreatment. CONCLUSIONS: This study
      demonstrates that NOS inhibitor L-NAME administration alone has insignificant
      effects on pulpal blood flow, although L-NAME pretreatment can potentiate SP
      induced vasodilatation, probably via increased activity in the enzyme guanylate
      cyclase. CGRP and papaverine did not respond to L-NAME pretreatment, indicating
      that they are not mediated via an endothelium-dependent mechanism.

PMID- 14641423
TI  - The influence of organic load on the antimicrobial activity of different
      concentrations of NaOCl and chlorhexidine in vitro.
AB  - AIM: To evaluate bacterial growth after contact with sodium hypochlorite (NaOCl;
      1 and 5%) and chlorhexidine (CHX; 0.12, 0.5 and 1%) in vitro with or without the
      addition of organic material (bovine serum albumin (BSA) 0.5%). METHODOLOGY:
      Bacterial samples (American Type Culture Collection (ATCC)) of Staphylococcus
      aureus, Enterococcus faecalis, Escherichia coli, Porphyromonas gingivalis and
      Fusobacterium nucleatum were kept in contact with each irrigating solution for
      varying intervals of time: immediately (t0), 5 min (t5), 15 min (t15) and 30 min
      (t30). Each test was repeated 10 times. In half of the specimens, 0.5% BSA was
      added as organic material in an attempt to simulate the organic tissue present in
      the root canal system. Bacterial growth under appropriate condition of incubation
      was evaluated and compared for each microorganism at all time intervals. RESULTS:
      A 0.12% CHX solution did not eliminate E. faecalis at any time interval. One
      percent CHX eliminated all strains, as did both NaOCl concentrations. BSA did not
      interfere substantially with the antimicrobial activity of any of the irrigating
      solutions. CONCLUSIONS: Under the condition of this study, a 0.12% CHX solution
      was ineffective at killing E. faecalis.

PMID- 14641424
TI  - Lymphangiogenesis in human dental pulp.
AB  - AIM: To investigate the impact of inflammation on lymphangiogenesis in human
      dental pulp. METHODOLOGY: Eleven samples of dental pulp without inflammation and
      11 dental pulps with moderate to intense mononuclear cell inflammatory infiltrate
      associated with dentine caries were selected. The streptavidin-biotin complex
      stain was used to detect CD31, vascular endothelial growth factor receptor-3
      (VEGFR-3) and alpha-smooth muscle actin. The number of lymphatic vessels was
      obtained by counting the number of vessels positive for CD31 and VEGFR-3 and
      negative for alpha-smooth muscle actin. RESULTS: The results demonstrated that
      the mean number (+/-SD) of vessels positive for CD31 and VEGFR-3 (lymphatic
      vessels) in the group with inflammation (6.09 +/- 1.81) was statistically higher
      (P = 0.0123) than the mean number in the group without inflammation (3.73 +/-
      2.20). CONCLUSION: Increased co-immunostaining of CD31 and VEGF-3 in vessels
      associated with human dental pulp inflammation occurred, which suggests
      lymphangiogenesis.

PMID- 14641425
TI  - Comparative in vivo analysis of the sealing ability of three endodontic sealers
      in post-prepared root canals.
AB  - AIM: To compare the sealing ability of the endodontic sealers AH Plus, Sealer 26
      and Endofill in premolar teeth of dogs exposed to the oral cavity after post
      preparation. METHODOLOGY: Forty teeth with two canals each underwent root canal
      cleaning and shaping. Before filling, the canals were randomly distributed into
      three groups according to the sealer to be used: Group 1 - AH Plus; Group 2 -
      Sealer 26; and Group 3 - Endofill (Dentsply, Industria e Comercio Ltda.).
      Immediately after filling, the gutta percha and sealer were partially removed
      from the canals, leaving material only in the apical third of the root. The teeth
      were temporarily sealed with glass ionomer sealer for 72 h to ensure setting. The
      coronal seal was then removed and the canals were exposed to the oral cavity for
      45 days. The animals were euthanased and their mandibles and maxillae were
      removed. After abundant irrigation with distilled water, the canals were dried
      and filled with India ink. The teeth were sealed again for 96 h before
      extraction. The roots of the extracted premolars were separated and stored in
      labelled test tubes. The roots were cleared and the extent of dye penetration was
      measured with a 20x stereoscopic magnifying lens. RESULTS: Statistical analysis
      revealed that there were significant differences between the sealers studied (P <
      0.001). Means for the extent of dye penetration for AH Plus, Endofill and Sealer
      26 were, respectively, 0.13, 2.27 and 3.08 mm. CONCLUSIONS: After 45 days
      exposure to the oral cavity, none of the sealers was capable of preventing
      leakage and coronal dye penetration. There were significant differences between
      the sealers studied, in terms of mean dye penetration.

PMID- 14641426
TI  - Incidence of rotary ProFile instrument fracture and the potential for bypassing
      in vivo.
AB  - AIM: To determine the incidence of rotary ProFile instrument fracture and the
      potential for bypassing in molar teeth in vivo. METHODOLOGY: Four hundred and
      nineteen maxillary and mandibular first and second molars (1457 canals) were
      cleaned and shaped by two endodontists with new and used sets of nickel-titanium
      ProFile.04 taper rotary instruments. Each set of instruments was used in five
      molars and was steam-autoclaved before use. The canals were instrumented using
      passive instrumentation and a crown-down preparation technique. Instruments were
      examined both before and after use to evaluate whether breakage or deformation
      had occurred. All canals were instrumented to at least a size 30 at the working
      length. RESULTS: Nineteen instruments demonstrated visible signs of plastic
      deformation and were discarded and replaced, whilst 21 instruments underwent
      intracanal fracture during treatment. Amongst these, 14 fractured in the apical
      third, whilst the remaining seven fractured in the middle third. Seven
      instruments were bypassed, and treatment was completed. There was a significantly
      greater number of instrument fractures with the size 20 ProFile than with the
      other sizes, especially after the second time of use (P < 0.05). CONCLUSIONS:
      Prolonged clinical use of ProFile nickel-titanium instruments increased their
      fracture rate. One-third of fractured instruments were bypassed.

PMID- 14641427
TI  - The relationship of intracanal medicaments to postoperative pain in endodontics.
AB  - AIM: To investigate the relationship of postoperative pain to three different
      medicaments placed in the root canal after a complete biomechanical debridement
      of the root canal system in patients presenting for emergency relief of pain.
      METHODOLOGY: Two hundred and twenty-three teeth belonging to 221 patients
      presenting as emergencies to the Royal Dental Hospital of Melbourne were included
      in the study. Inclusion was limited to patients with a diagnosis of pulp necrosis
      and acute apical periodontitis. All teeth underwent conventional root canal
      treatment, which involved the instrumentation to the apices of each canal at the
      first visit. Canals were instrumented using a stepback technique and hand-files
      along with irrigants using Milton's (1% sodium hypochlorite) solution followed by
      15% EDTAC. The canals were dried and one of the following three medicaments was
      inserted into the canal in random sequence: Group 1: Ledermix paste (Lederle
      Pharmaceuticals, Division of Cyanamid, Wolfratshausen, Germany); Group 2: calcium
      hydroxide paste (Calcipulpe, Septodont, France); and Group 3: no dressing. Before
      dismissal, the preoperative pain experienced on the previous night was recorded
      using a visual analogue pain scale. Patients were then instructed to record the
      degree of pain experienced 4 h after treatment and daily for a further 4 days.
      RESULTS: The mean score pain for all three groups was between 42 and 48 prior to
      treatment being commenced. After 4 days, the pain score for Group 2 was 10, for
      Group 3 was 7 and for Group 1 was 4. Mean preoperative pain level was 44.4 (of a
      maximum 100) for all groups, and declined by 50% (to 22.1) after 24 h. Patients
      in Group 1 (Ledermix) experienced significantly less (P = 0.04) postoperative
      pain than those in the other two groups. There was no significant difference
      between Group 2 (calcium hydroxide) and Group 3 (no dressing). CONCLUSION: Under
      the conditions of this study, painful teeth with acute apical periodontitis that
      had been dressed with Ledermix paste gave rise to less pain than that experienced
      by patients who had a dressing of calcium hydroxide or no dressing at all.
      Ledermix is an effective intracanal medicament for the control of postoperative
      pain associated with acute apical periodontitis, with a rapid onset of pain
      reduction.

PMID- 14641428
TI  - Comparison of MicroSeal and System B/Obtura II obturation techniques.
AB  - AIM: To compare the proportion of gutta-percha, sealer and voids following the
      filling of simulated root canals in plastic blocks using two warm gutta-percha
      techniques. METHODOLOGY: Ten simulated root canals in plastic blocks were
      prepared using System GT Rotary Files and a.02 taper size 40 Quantec rotary
      nickel-titanium instrument and then filled with MicroSeal and Kerr EWT sealer. A
      further 10 simulated canals were prepared solely with System GT Rotary Files and
      obturated with System B/Obtura II and Kerr EWT sealer. All blocks were sectioned
      at 1 mm intervals. The sectioned root fillings were photographed through a
      stereomicroscope and the resultant slides scanned. The images were analysed using
      adobe photoshop 6.0 to give the proportions of gutta-percha, sealer or void at
      each level. The data were analysed using unpaired Student's t-test and Mann
      Whitney U-test. RESULTS: The MicroSeal technique produced a dense homogeneous
      gutta-percha fill at the apical 1 and 2 mm levels similar to the System B/Obtura
      II technique, but further coronally the sealer became mixed into the MicroFlow
      gutta-percha producing a heterogeneous mass with significantly less (P < 0.05)
      solid gutta-percha in the root filling compared to System B/Obtura II. The
      MicroSeal technique generally had more pooling of cement than the System B
      technique, however, this was only significantly different (P < 0.05) at the 4 mm
      level. The System B/Obtura II obturation gave an average of 99.27% +/- 1.09 gutta
      percha fill at all levels. CONCLUSIONS: The MicroSeal technique produced a
      heterogeneous fill consisting of the MicroFlow Master Cone and gutta-percha from
      the MicroFlow Cartridge mixed with sealer. The System B/Obtura II technique
      produced a homogeneous fill at all levels.

PMID- 14641429
TI  - Root canal preparation with FlexMaster: asessment of torque and force in relation
      to canal anatomy.
AB  - AIM: To investigate physical parameters of FlexMaster nickel-titanium instruments
      while preparing curved canals in maxillary molars in vitro. METHODOLOGY: A torque
      testing platform was used to prepare root canals in 11 extracted human maxillary
      molars with FlexMaster rotary instruments. Peak torque and force was registered
      along with numbers of rotations required to shape the canals. Canals were divided
      into 'wide' and 'constricted' groups depending on canal volumes assessed by
      microcomputed tomography. Resistance to cyclic fatigue was also tested. Mean
      scores for each instrument type were calculated and statistically compared using
      anova and Scheffe post hoc tests. RESULTS: Mean torque varied between 0.1 +/- 0.1
      and 0.8 +/- 0.5 N cm while mean force ranged from 4.2 +/- 2.0 to 7.3 +/- 3.5 N.
      Mean numbers of rotations totalled up to 18. All three variables registered
      showed weak correlations to preoperative canal volumes (P < 0.01) and differed
      significantly between 'wide' and 'constricted' canals (P < 0.001). Numbers of
      rotations to fracture in a cyclic fatigue test were between 348 and 1362.
      CONCLUSION: FlexMaster instruments generated low torque scores and were highly
      resistant to cyclic fatigue, whilst three instruments fractured in extremely
      narrow canals. Consequently, more research is required to limit fracture
      incidence and to optimize instrumentation guidelines.

PMID- 14641430
TI  - Comparison of neurotoxicity of root canal sealers on spontaneous bioelectrical
      activity in identified Helix neurones using an intracellular recording technique.
AB  - AIM: To evaluate the neurotoxic effects of two endodontic sealers, AH-26 and Roth
      801, on firing excitability and action potential configuration of F1 neural cells
      in the suboesophageal ganglia of Helix aspersa. METHODOLOGY: A conventional
      intracellular current clamp technique was used to study the blocking effects of
      AH-26 and Roth 801 on ionic currents underlying the action potential of F1 nerve
      cells. The sealers were prepared according to the manufacturers' directions and
      were applied to the bathing media in two ways: invasive (0.05 mL of total mixture
      of each sealer was applied at a distance of 3 mm from the cell), or gradual (0.05
      mL of the extract of each dissolved mixture of sealers in normal Ringers solution
      was perfused). RESULTS: When applied in an invasive mode, both sealers reduced
      the duration, the amplitude of action potentials and the amplitude of after
      hyperpolarization potentials significantly and led to dramatic changes in action
      potential configuration. In the gradual mode of application, AH-26 showed a
      biphasic action; it first increased the excitability and then decreased the
      action potential parameters, while Roth 801 exhibited solely blocking effects.
      CONCLUSIONS: Both sealers had significant inhibitory effects on excitability of
      F1 neuronal cells.

PMID- 14641431
TI  - Visual endodontics & traumatology.

PMID- 14641434
TI  - Root-canal shaping with manual and rotary Ni-Ti files performed by students.
AB  - AIM: To investigate root-canal shaping with manual and rotary Ni-Ti files
      performed by students. METHODOLOGY: Thirty undergraduate dental students prepared
      150 simulated curved root canals in resin blocks with manual Ni-Ti files with a
      stepback technique and 450 simulated curved canals with rotary Ni-Ti files with a
      crowndown technique. Incidence of fracture, preparation length, canal shape and
      preparation time were investigated. Questionnaires were then issued to the
      students for them to note their experience of the two preparation methods.
      RESULTS: Zips and elbows occurred significantly (P < 0.001) less frequently with
      rotary than with manual preparation. The correct preparation length was achieved
      significantly (P < 0.05) more often with rotary files than with manual files.
      Instrument fractures were recorded in only 1.3% of cases with both rotary and
      manual preparation. The mean time required for manual preparation was
      significantly (P < 0.001) longer than that required for rotary preparation. Prior
      experience with a hand preparation technique was not reflected in an improved
      quality of the subsequent rotary preparation. Approximately 83% of the students
      claimed to have a greater sense of security in rotary than in manual preparation.
      Overall 50% felt that manual and engine-driven preparation should be given equal
      status in undergraduate dental education. CONCLUSIONS: Inexperienced operators
      achieved better canal preparations with rotary instruments than with manual
      files. No difference in fracture rate was recorded between the two systems.

PMID- 14641435
TI  - The effect of cleaning procedures on fracture properties and corrosion of NiTi
      files.
AB  - AIM: To evaluate the effect of repeated cleaning procedures on fracture
      properties and corrosion of nickel-titanium (NiTi) files. METHODOLOGY: New NiTi
      instruments were subjected to 2, 5 and 10 cleaning cycles with the use of either
      diluted bleach (1% NaOCl) or Milton's solution (1% NaOCl plus 19% NaCl) as
      disinfectant. Each cleaning cycle consisted of scrubbing, rinsing and immersing
      in NaOCl for 10 min followed by 5 min of ultrasonication. Files were then tested
      for torsional failure and flexural fatigue, and observed for evidence of
      corrosion using scanning electron microscope (SEM). Four brands of NiTi files
      were immersed in either Milton's solution or diluted bleach overnight and
      evaluated for corrosion. RESULTS: Up to 10 cleaning cycles did not significantly
      reduce the torque at fracture or number of revolutions to flexural fatigue (P >
      0.05, two-way anova), although decreasing values were noted with increasing
      number of cleaning cycles using Milton's solution. No corrosion was detected on
      the surface of these files. Files immersed in 1% NaOCl overnight displayed a
      variety of corrosion patterns. The extent of corrosion was variable amongst
      different brands of files and amongst files in each brand. Overall, Milton's
      solution was much more corrosive than diluted bleach. Corrosion of file handles
      was often extreme. CONCLUSIONS: Files can be cleaned up to 10 times without
      affecting fracture susceptibility or corrosion, but should not be immersed in
      NaOCl overnight. Milton's solution is much more corrosive than bleach with the
      same NaOCl concentration.

PMID- 14641436
TI  - Effect of different irrigation solutions and calcium hydroxide on bacterial LPS.
AB  - AIM: To evaluate the effect of biomechanical preparation with different
      irrigating solutions and calcium hydroxide dressing in dog root canals containing
      bacterial endotoxin (lipopolysaccharides; LPS). METHODOLOGY: One hundred and
      forty premolar roots from seven dogs were filled with Escherichia coli LPS for 10
      days (three roots were lost during histological processing). The following
      irrigating solutions were used for biomechanical preparation: 1% (group I, n =
      20), 2.5% (group II, n = 19) and 5% sodium hypochlorite (group III, n = 19), 2%
      chlorhexidine digluconate (group IV, n = 20) and physiological saline solution
      (group V, n = 19). In group VI (n = 20), the LPS solution was maintained in the
      root canal during the entire experiment and in group VII (n = 20), after
      biomechanical preparation with saline solution, the root canals were filled with
      a calcium hydroxide dressing (Calen; control). After 60 days, the animals were
      sacrificed and the following parameters of periapical disease were evaluated: (a)
      inflammatory infiltrate, (b) periodontal ligament thickness, (c) cementum
      resorption and (d) bone resorption. Scores were given and data were analysed
      statistically with the Kruskal-Wallis and Dunn tests (P < 0.05). RESULTS:
      Histopathological evaluation showed that groups I-VI had more inflammatory
      infiltrate, greater periodontal ligament thickening and greater cementum and bone
      resorption (P < 0.05) compared to group VII, which received the calcium hydroxide
      intracanal dressing. CONCLUSIONS: Biomechanical preparation with the irrigating
      solutions did not inactivate the effects of the endotoxin but the calcium
      hydroxide intracanal dressing did appear to inactivate the effects induced by the
      endotoxin in vivo.

PMID- 14641437
TI  - Root-canal preparation with FlexMaster: canal shapes analysed by micro-computed
      tomography.
AB  - AIM: To evaluate the relative performance of FlexMaster nickel-titanium
      instruments shaping maxillary molar root canals in vitro. METHODOLOGY: Extracted
      human maxillary molars were scanned, before and after root-canal shaping, with
      FlexMaster, employing micro-computed tomography (microCT) at a resolution of 36
      microm. Canals were three-dimensionally reconstructed and evaluated for volume,
      surface area, 'thickness' (diameter), canal transportation and prepared surface.
      Based on median canal volume, the canals were divided into 'wide' and
      'constricted' groups. Comparisons were made between mesiobuccal (mb), distobuccal
      (db) and palatal (p), as well as 'wide' and 'constricted' canals, using anova and
      Scheffe post-hoc tests. RESULTS: Volume and surface area increased significantly
      and similarly in mb, db and p canals, and no gross preparation errors were found.
      Mean root-canal diameters, 5 mm coronal to the apex, increased from 0.45 to 0.65
      mm, from 0.41 to 0.56 mm and from 0.79 to 0.85 mm for mb, db and p canals,
      respectively. Apical canal transportation ranged from 0.01 to 0.29 mm and was
      independent of canal type; 'wide' canals had a significantly higher (P < 0.05)
      proportion of unprepared surfaces than 'constricted' canals had. CONCLUSIONS:
      FlexMaster instruments shaped curved and narrow root canals in maxillary molars
      to sizes 40 and 45 without significant shaping errors. Canal anatomy had an
      insignificant impact on preparation, indicating that FlexMaster instruments were
      able to shape 'constricted' canals as well as 'wide' ones.

PMID- 14641438
TI  - Comparative study of root-canal preparation using Lightspeed and Quantec SC
      rotary NiTi instruments.
AB  - AIM: To compare several parameters of root-canal preparation using two different
      rotary nickel-titanium (NiTi) instruments: Lightspeed (Lightspeed Inc, San
      Antonio, TX, USA) and Quantec SC (Tycom, Irvine, USA). METHODOLOGY: Fifty
      extracted mandibular molars with root-canal curvatures between 20 degrees and 40
      degrees were embedded into a muffle system. All root canals were prepared to size
      45 followed by a stepback in 1-mm increments to size 70 (Lightspeed) or 45
      (Quantec SC), using a high-torque motor at 1300 or 350 r.p.m. respectively. In
      both groups, irrigation was performed with 2 mL NaOCl (3%) after each instrument
      size. RC-Prep (Premier, PA, USA) was used as a chelating agent. The following
      parameters were evaluated: straightening of curved root canals, postoperative
      root-canal diameter, working safety (instrument fractures, perforations, apical
      blockages, loss of working length (WL)), cleaning ability and working time.
      Cleanliness of the root-canal walls was investigated under SEM using 5-score
      indices for debris and smear layer. Statistical analysis was performed using the
      Wilcoxon's test (P < 0.05) for straightening and Fisher's exact test (P < 0.05)
      for comparison of cross-sections, contact between pre- and postoperative
      diameter, root-canal cleanliness and working time. RESULTS: Both NiTi systems
      maintained the curvature well: the mean degree of straightening was 1.8 degrees
      for Lightspeed and 1.7 degrees for Quantec SC; differences were not significant.
      Procedural incidents occurred with Quantec SC in 12 root canals (three fractures,
      four apical blockages and five cases of loss of WL), preparation with Lightspeed
      resulted in five fractures, one apical blockage and five cases of loss of WL (11
      incidents). Following preparation with Lightspeed, 55.5% of the root canals had a
      round diameter, 25% an oval and 19.5% an irregular diameter; Quantec SC
      preparations resulted in a round diameter in 51.5%, oval shape in 33.3% and
      irregular cross-sections in 15.2% of the cases. Mean working time was similar for
      Quantec SC (161 s) and Lightspeed (155 s); the difference was not significant.
      For debris, Lightspeed and Quantec achieved 64 and 63% for scores 1 and 2,
      respectively. For smear layer, Lightspeed and Quantec achieved only 13.3 and
      27.4% for scores 1 and 2, respectively. Differences were not significant for
      either debris or smear layer. CONCLUSIONS: Both systems respected original root
      canal curvature well and prepared acceptable diameter forms. The cleaning ability
      was judged not satisfactory for both systems. Both systems showed deficiencies in
      working safety.

PMID- 14641439
TI  - Coronal pulp size in molars: a study of bitewing radiographs.
AB  - AIM: To: (i) study coronal pulp dimensions in human first molar teeth; (ii)
      investigate the effects of restorations on pulp size; (iii) determine differences
      in dimensions between teeth of Mongoloid patients and teeth of other ethnic
      groups; and (iv) record the presence of pulp stones. METHODOLOGY: Bitewing
      radiographs of 121 subjects (mean age, 20.9 years) were taken under standardized
      conditions. The films were digitally scanned and nine measurements were made from
      the image of each first molar. The data were analysed in terms of presence or
      absence of restorations and in terms of racial group. Differences were examined
      using Student's t-test, Pearson correlations and Levene's test. RESULTS: A total
      of 445 teeth were analysed. Large crowns were correlated to large pulps. Teeth
      restored with occlusal and proximal restorations had significantly smaller pulps
      (P = 0.044 and 0.004, respectively), but no difference was found in pulp area in
      the clinical crown between the restoration types. Mongoloid crowns were shorter
      and more bulbous. Pulp areas of maxillary molars and pulp widths at the cervix of
      mandibular molars were significantly larger in Mongoloids. The pulp area in the
      clinical crown correlated to pulp horn height for Mongoloids and others and for
      maxillary and mandibular teeth. No differences were found between the heights of
      pulp horns in the Mongoloid and other teeth. Four of the pulp measurements
      demonstrated sexual dimorphism. Stones were present in almost 10% of the
      subjects, representing 4% of the tooth pulps examined. CONCLUSION: Even teeth
      with shallow occlusal restorations had reduced pulp spaces. There were
      significant differences in pulp and crown dimensions between the teeth of
      Mongoloid patients and those of other patients.

PMID- 14641440
TI  - An in vitro study of the torsional properties of new and used K3 instruments.
AB  - AIM: To compare torque and angle of rotation at fracture of new and used K3
      rotary instruments. The relation between size of instrument and torque at
      fracture was also investigated. METHODOLOGY: Nickel-titanium (Ni-Ti).06 K3 rotary
      instruments were used in a crown-down manner at 300 r.p.m. to prepare canals in
      resin blocks. The torque and angle of rotation at fracture of new and the used Ni
      Ti.06 K3 rotary instruments (sizes 15-40) were determined according to ANSI/ADA
      Specification no. 28. Analysis of variance was used to compare the torque and
      angle of rotation at fracture amongst the different sizes of the new instruments
      and between new instruments and instruments of the same size, which had been used
      in resin blocks (alpha = 0.05). The relationship between torque at fracture and
      size of instrument was subjected to regression analysis. RESULTS: Torque at
      fracture of the new instruments increased significantly with the diameter. The
      used instruments (sizes 15, 20, 30, 35 and 40) had lower torque at fracture
      compared to the new ones (P < 0.0001). The means of angle of rotation at fracture
      between the different sizes of new instruments were significantly different (P <
      0.0001) except for sizes 15-20 (P = 0.2561). The used instruments (sizes 20-40)
      had lower angle of rotation at fracture compared to the new ones (P < 0.05). A
      linear relationship was found between the size of the file and the torque at
      fracture for the new instruments (r2 = 0.84; P < 0.0001) and the used ones (r2 =
      0.82; P < 0.0001). CONCLUSIONS: In general, the results suggested that the torque
      and angle of rotation at fracture were significantly affected by the repeated use
      of.06 K3 instruments in resin blocks.

PMID- 14641441
TI  - In vitro fracture resistance of root-filled teeth using new-generation dentine
      bonding adhesives.
AB  - AIM: To compare the fracture resistance of root-filled premolar teeth restored
      with new-generation dentine bonding adhesives. METHODOLOGY: Sixty extracted
      single-rooted human maxillary premolar teeth were used. Access cavities were
      prepared, and the roots were instrumented with K-files to an apical size 50 using
      a step-back technique. Root fillings were accomplished using gutta percha (Sure
      Endo, Seoul, Korea) and AH Plus root canal sealer (Dentsply DeTrey, Konstanz,
      Germany) using the lateral condensation technique. The teeth were then randomly
      divided into six groups of 10 teeth each. A mesiodistocclusal (MOD) cavity was
      prepared in the teeth to the level of the canal orifices so that the thickness of
      the buccal wall of the teeth measured 2 mm at the occlusal surface and 3 mm at
      the cemento-enamel junction. Preparations were restored using the following
      adhesive systems: Etch & Prime 3.0 (Degussa AG, Hanau, Germany), Clearfil SE Bond
      (Kuraray, Osaka, Japan), Prompt L-Pop (ESPE, Seefeld, Germany), Panavia F
      (Kuraray, Osaka, Japan), Optibond Plus (Kerr, Orange, CA, USA) and Admira Bond
      (Voco, Cuxhaven, Germany); all preparations except those of the Panavia F and
      Admira Bond groups were further restored with resin composites. The Panavia F
      group was restored with amalgam and the Admira Bond group with Ormocer (Voco,
      Cuxhaven, Germany). The teeth were mounted in a Universal Testing Machine
      (Hounsfield, Surrey, UK), and the buccal walls were subjected to a slowly
      increasing compressive force until fracture occurred. The force of fracture of
      the walls of each tooth was recorded and the results in the various groups were
      compared. Statistical analysis of the data was accomplished using one-way anova.
      RESULTS: There was no significant difference in the fracture resistance of any of
      the test groups. CONCLUSIONS: In this laboratory study, the type of dentine
      bonding agents had no influence in the fracture resistance of teeth.

PMID- 14641442
TI  - Induction of interleukin-8 gene expression by black-pigmented Bacteroides in
      human pulp fibroblasts and osteoblasts.
AB  - AIM: To investigate the effect of black-pigmented Bacteroides on the expression
      of interleukin (IL)-8 gene in human pulp fibroblasts and osteoblasts.
      METHODOLOGY: The supernatants of Porphyromonas endodontalis, P. gingivalis and
      Prevotella intermedia were used to evaluate IL-8 gene expression in human pulp
      fibroblasts and osteoblasts. The levels of mRNAs were measured by the
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.
      RESULTS: Investigations of the time-dependence of IL-8 mRNA expression in black
      pigmented Bacteroides-treated pulp fibroblasts and osteoblasts revealed a rapid
      accumulation of the transcript after 2 h of exposure, and remained elevated
      throughout the 24-h incubation period. In addition, IL-8 mRNA gene expression was
      also found in human osteoblasts stimulated with black-pigmented Bacteroides.
      However, black-pigmented Bacteroides was found to be more effective in the
      induction of IL-8 mRNA gene expression in osteoblasts than in pulp fibroblasts (P
      < 0.05). CONCLUSIONS: Black-pigmented Bacteroides are capable of amplifying the
      local immune response and promoting pulpal/periapical tissue inflammation by
      stimulating pulp fibroblasts and osteoblasts to express IL-8.

PMID- 14641443
TI  - Bacterial status in root-filled teeth exposed to the oral environment by loss of
      restoration and fracture or caries--a histobacteriological study of treated
      cases.
AB  - AIM: To describe histological and microbiological findings in teeth where root
      fillings had been exposed to caries and the oral environment for a prolonged
      period. METHODOLOGY: For inclusion in the study, only teeth with a follow-up
      period of 3 years or more and those that had been without proper restoration for
      at least a period of 3 months were considered. Some root fillings had been
      without restoration for several years. In all, 39 roots representing 32 teeth
      were examined by histology. RESULTS: The majority of the specimens were without a
      discernible periapical bone lesion as assessed by radiography. Osteolytic lesions
      were seen with five roots. Longitudinal tissue sections stained with a modified
      Brown/Brenn staining technique revealed presence of stainable bacteria in
      abundance at the canal entrance and in dentinal tubules but were absent mid-root
      and apically in all but two specimens. Soft tissue attached to the root tip and
      in apical ramifications displayed distinct inflammatory cell infiltrates,
      suggesting microbial exposure in 7 of the 39 roots examined. In all other
      specimens, inflammatory cell infiltrates were either nonexistent or sparse and
      then associated with extruded sealer material. CONCLUSIONS: Well-prepared and
      filled root canals resist bacterial penetration even upon frank and long-standing
      oral exposure by caries, fracture or loss of restoration.

PMID- 14641444
TI  - Annual Congress for the British Society for Immunology, 2-5 Dec 2003, Harrogate,
      United Kingdom. Abstracts.

PMID- 14641466
TI  - A new karyotype of Oligoryzomys (Sigmodontinae, Rodentia) from central Brazil.
AB  - A new karyotype of the genus Oligoryzomys was described for specimens collected
      in Brazilian Cerrado in Tocantins and Goias States. Conventional staining, G-, C
      banding, and Ag-NOR staining techniques were used for describe this karyotype
      with 2n=70, AN=74 or 76. The chromosome complement, with the highest diploid
      number known among Oligoryzomys species, differs from all others previously
      reported. This small sized Oligoryzomys species can be differentiated from other
      Brazilian Oligoryzomys not only by chromosomal complement, but also in some
      morphological attributes. The new species is apparently restricted in
      distribution and endemic of Brazilian Cerrado, occurring only in Rio Tocantins
      basin.

PMID- 14641467
TI  - Highly variable social organisation of colonies in the ant Formica cinerea.
AB  - Social organisation of colonies was examined in the ant Formica cinerea by
      estimating the coefficient of genetic relatedness among worker nest mates. The
      estimates based on microsatellite genotypes at three loci ranged from values
      close to zero to 0.61 across the populations studied in Finland. These results
      showed that a fundamental feature of colonies, the number of reproductive queens,
      varied greatly among the populations. Colonies in some populations had a single
      queen, whereas the nests could have a high number number of queens in other
      populations. There was a weak but non-significant correlation between the genetic
      and metric distance of nests within two populations with intermediate level of
      relatedness. Differentiation among nearby populations (within the dispersal
      distance of individuals) in one locality indicated limited dispersal or founder
      effects. This could occur when females are philopatric and stay in the natal
      polygynous colony which expands by building a network of nest galleries within a
      single habitat patch.

PMID- 14641468
TI  - Karyotype evolution in South American subterranean rodents Ctenomys magellanicus
      (Rodentia: Octodontidae): chromosome rearrangements and (TTAGGG)n telomeric
      sequence localization in 2n=34 and 2n=36 chromosomal forms.
AB  - Ctenomys is the most numerous genus of South American subterranean rodents and
      one of the most karyotypically diverse clades of mammals known. Ctenomys
      magellanicus is the southernmost species of the group and the only one living in
      Isla Grande de Tierra del Fuego (Argentina). This species presents two
      chromosomal forms, i.e. 2n=34, and 2n=36 (FN=68). Recent studies suggest that
      genetic divergence between both karyotypic forms resulted from a chromosomal
      speciation process. In order to identify the chromosomal rearrangement involved
      in the process of karyotype evolution in this species, we used chromosome banding
      techniques and fluorescence in situ hybridization with a telomeric probe to
      metaphase chromosomes of the two chromosomal forms of Ctenomys magellanicus.
      Chromosome analysis of Giemsa-stained and G-banding preparations showed that Cm34
      and Cm36 karyotypes differ in one rearrangement involving chromosomes A9 from
      Cm34 and B12 and B17 from Cm36. In addition FISH analysis showed that all of the
      chromosomes from both chromosomal forms exhibit a telomeric-only distribution
      pattern of the (TTAGGG)n sequence, indicating that none of the chromosomal forms
      of Ctenomys magellanicus has true telocentric chromosomes. Our results suggest
      that a chromosome fission event would have occurred during the process of
      karyotype evolution in this species.

PMID- 14641469
TI  - Genetic diversity in wild Spanish populations of Thinopyrum junceum and
      Thinopyrum junceiforme using endosperm proteins and PCR-based markers.
AB  - The genetic variation of sixteen wild, Spanish populations of Thinopyrum junceum
      and Thinopyrumjunceiforme and their interspecific relationships were analyzed.
      The relationships between these species and the diploids T. bessarabicum and T.
      elongatum were also investigated. The number of phenotypes and the composition of
      bands yielded by the electrophoretic separation of endosperm proteins were used
      to estimate intra- and interpopulational variability. DNA polymorphism generated
      by 24 arbitrary 10-mer primers and 14 specific 20-mer primers was used to
      determine interpopulational variability and interspecific relationships.
      Jaccard's coefficient of similarity was used to analyze presence and absence data
      in the DNA polymorphism and endosperm protein determinations of individual
      plants. Pearson's product-moment correlation coefficient was used to analyse
      interpopulational variation using endosperm protein band frequency data.
      Dendrograms were constructed using an unweighted pair group method with
      arithmetical average (UPGMA). The high level of intrapopulational variability
      found in T. junceum and T. junceiforme was inconsistent with the traditional
      classification of these species as self-pollinating. The level of
      interpopulational variation varied according to the degree of polymorphism of the
      corresponding markers. The endosperm proteins and random amplified polymorphic
      DNAs (RAPDs) proved to be the most polymorphic markers to those used although
      only the former were able to distinguish between the different populations.
      Interspecific relationships were consistently confirmed by all the PCR-based
      markers, and were also in agreement with the results of other authors.

PMID- 14641470
TI  - Higher-order repeats in the satellite DNA of the cave beetle Pholeuon proserpinae
      glaciale (Coleoptera: Cholevidae).
AB  - The present study characterizes the satellite DNA of the cave beetle Pholeuon
      proserpinae glaciale which represent about 3-5 % of its genome, and which is
      composed of monomers of 266 bp and 70.5 % A-T. Concerted evolution seems to act
      on a higher-order repeat, a dimer, composed of two types of 266-bp monomers that
      differ in three diagnostic sites. These dimers show a striking nucleotide
      identity (98.7 % similarity) suggesting strong homogenization processes. The
      presence of particular mutations shared by several dimers represents an early
      expansion of these types of repeats as proposed by the molecular drive model.
      Moreover, evidence of gene conversion tracts in P. proserpinae glaciale, which
      also could be the result of unequal sister chromatid exchange, would suggest that
      recombination is involved in the homogenization of stDNA sequences. The presence
      of a 17-bp-motif repeated six times, along another one of 31-bp repeated twice
      which also have embedded one 17-bp-motif, suggest that monomers have originated
      from those basic motifs.

PMID- 14641471
TI  - Karyotypic analysis of two algae species Scenedesmus incrassatulus Bohl and
      Scenedesmus antennatus Breb (Chlorophyta, Chlorococcales).
AB  - The karyotypes (number, morphology and size of the chromosomes) of two algae
      species of Scenedesmus genus, S. incrassatulus and S. antennatus, were studied.
      The karyotype of S. incrassatulus (n=4) was asymmetric, characterized by two
      large metacentric, one large submetacentric and one small metacentric
      chromosomes. The karyotype assembly of S. antennatus (n=6) reveals two
      metacentrics and four submetacentrics. This karyotype was symmetric. The general
      chromosomal formulae of both species, as well as the total average metaphase
      length of their haploid set are presented. The results of chromosomal studies of
      other related species are compared and discussed. Data from the karyotypic
      analysis showed that S. incrassatulus, S. antennatus and S. obliquus are separate
      biological species from taxonomical point of view.

PMID- 14641472
TI  - Timing of first feeding and life-history strategies in salmon: genetic data.
AB  - To investigate the relationship between genetic composition and some
      physiological traits of interest (age at smoltification, precocious maturation in
      male parr) in early and late first feeding Atlantic salmon, genetic variation at
      6 isozyme and 8 microsatellite loci was examined. Early and late first feeding
      salmon showed different allelic and genotypic distributions at both isozyme and
      microsatellite loci. A positive relation between enzymatic loci heterozygosity
      and precocious active alimentation and earlier smoltification (S1 cf. S2) were
      also found.

PMID- 14641473
TI  - Inheritance and expression of stripe rust resistance in common wheat (Triticum
      aestivum) transferred from Aegilops tauschii and its utilization.
AB  - Stripe rust is one of the most destructive diseases for wheat crops in China. Two
      stripe rust physiological strains, i.e. CYR30 (intern. name: 175E191) and CYR31
      (intern. name: 293E175) have been the dominant and epidemic physiological strains
      since 1994. One Aegilops tauschii accession (SQ-214) from CIMMYT was found immune
      from or highly resistant to Chinese new stripe rust races CYR30 and CYR31 at
      adult stage. SQ-214 was crossed with a highly susceptible Ae. tauschii accession
      As-80. Analysis of data from F1-F2 populations of SQ-214/As-80 revealed that the
      resistance was controlled by a single dominant gene. To exploit the resistance
      for wheat breeding, SQ-214 was crossed with Chinese Spring (CS) and backcrossed
      by two Chinese commercial wheat varieties MY26 and SW3243. The resistance from SQ
      214 was suppressed in the F1 hybrids (CS/SQ-214) and the F2 population of CS/SQ
      214//MY26. However, the resistance of SQ-214 was expressed in several F2
      individuals of CS/SQ-214//SW3243. Eleven advanced lines with high level of
      resistance to the Chinese stripe rust CYR30 and CYR31 have been developed. This
      result suggested that SW3243 does not suppress the expression of the Chinese
      stripe rust and should be used as wheat germplasm for exploiting resistance of
      Ae. tauschii in wheat breeding. The gliadin electrophoretic pattern of the eleven
      advanced lines with high stripe rust resistances was compared with their parents
      SQ-214, CS and SW3243 by acid polyacrylamide gel electrophoresis. The omega
      gliadin bands of Gli-Dt1 in Ae. tauschii SQ-214 were transferred to some advanced
      lines and freely expressed in common wheat genetic background. One of advanced
      lines possesses a null Gli-D1 allele, where the omega-gliadin bands encoding by
      the Gli-D1 allele were absent. The potential utilization of this advanced line
      for wheat quality and stripe rust resistance breeding is also discussed in this
      paper.

PMID- 14641474
TI  - Genetic diversity in Tanzanian Arabica coffee using random amplified polymorphic
      DNA (RAPD) markers.
AB  - DNA from Coffea arabica leaves was used for RAPD analysis and a total of 144 leaf
      samples collected from 16 provenances in five regions of Tanzania were analysed.
      Ten arbitrary 10 mer primers were employed in the analysis and they produced a
      total of 86 fragments. Fragment sizes ranged from 100-1400 bp. The resulting
      dissimilarity matrix revealed values ranging from 0.11 to 1, while the average
      was 0.66. The cophenetic matrix and the original dissimilarity matrix showed a
      significant correlation of 78%. Mean dissimilarity values within provenances
      showed a fairly uniform trend despite the large range from 0.31 to 0.65. The
      dendrogram based on genetic distances but showed two clusters with grouping of
      provenances similar to the dendrogram generated by Jaccard's coefficient.
      Bootstrap analysis showed low values, despite this, the resulting dendrogram
      grouped all provenances according to their geographical origin. The standard
      genetic distances were fairly uniform implying a narrow genetic base in the
      cultivated Arabica coffee.

PMID- 14641475
TI  - Evidence for a second gene for primary microcephaly at MCPH5 on chromosome 1.
AB  - Primary microcephaly has been mapped to five loci on different chromosomes. We
      present here the fine mapping of one of the loci, MCPH5, to a region of only 0.58
      Mb located at the 1q31.3-1q32.1 junction. A genome scan was performed on five
      families from the Netherlands and Jordania, with 14 patients affected by
      microcephaly. A maximum LOD score of 4.78 was found for marker D1S1660 at the
      MCPH5 locus. Haplotype analysis suggests that the gene causing microcephaly is
      located between markers D1S3469 and D1S1660, which excludes the previously
      reported ASPM gene.

PMID- 14641476
TI  - Inversion polymorphisms and natural selection in Trimerotropis pallidipennis
      (Orthoptera).
AB  - Grasshoppers have been much less studied than Drosophila when it comes to
      inversion polymorphisms, despite the occurrence of this rearrangement in several
      species of grasshoppers. In the present study, 354 males from a natural
      population of the New World species Trimerotropis pallidipennis, polymorphic for
      6 pericentric inversions in 4 chromosome pairs, were sampled at the beginning and
      at the end of the adult life span. This sampling, along with the fact that
      generations in this grasshopper are annual and discrete, was done to detect
      differential adult male longevity among karyotypes and departures from formal
      null models, such as gametic phase equilibrium. These methods allow the detection
      of natural selection taking place in the wild. The comparison between age classes
      showed that some inversions were significantly more frequent in one sample, thus
      revealing the operation of natural selection. Gametic phase disequilibrium was
      detected in the sample of aged males but not in the sample of young ones.
      Furthermore, here we aim to detect the phenotypic targets of longevity selection
      by examining morphometric characters, in order to have a clearer idea of the
      relation between inversions and natural selection in this species. These results
      corroborate previous studies that suggested that the inversions are involved in
      natural selection, and an adaptive model has been proposed for the pattern of
      inversion frequencies throughout several populations at different altitudes and
      latitudes.

PMID- 14641477
TI  - Homology of primate DNA fragments for estrous-associated oviductal glycoprotein.
AB  - In this study, the DNA fragments encoded for oviduct EGP were amplified by PCR
      method. Corresponding sequences from chimpanzee, orangutan and human were
      similarly amplified, but we failed to amplify the corresponding DNA sequences
      from: spider monkey, salmon and several different species of rodents, bandicoot,
      sheep and pig. Through analyzing the restriction enzyme map and the DNA sequence
      of the amplified fragments from primates, the data suggest that monkey and human
      DNA encoded for EGP are genetically more closely related to one another than each
      of them to other species.

PMID- 14641478
TI  - Non-destructive genetic sampling in fish. An improved method for DNA extraction
      from fish fins and scales.
AB  - DNA-based studies have been one of the major interests in conservation biology of
      endangered species and in population genetics. As species and population genetic
      assessment requires a source of biological material, the sampling strategy can be
      overcome by non-destructive procedures for DNA isolation. An improved method for
      obtaining DNA from fish fins and scales with the use of an extraction buffer
      containing urea and further DNA purification with phenol-chloroform is described.
      The methodology combines the benefits of a non-destructive DNA sampling and its
      high efficiency. In addition, comparisons with other methodologies for isolating
      DNA from fish demonstrated that the present procedure also becomes a very
      attractive alternative to obtain large amounts of high-quality DNA for use in
      different molecular analyses. The DNA samples, isolated from different fish
      species, have been successfully used on random amplified polymorphic DNA (RAPD)
      experiments, as well as on amplification of specific ribosomal and mitochondrial
      DNA sequences. The present DNA extraction procedure represents an alternative for
      population approaches and genetic studies on rare or endangered taxa.

PMID- 14641479
TI  - Angiotensin converting enzyme gene polymorphism and traditional Sasang
      classification in Koreans with cerebral infarction.
AB  - Sasang constitutional medicine is a major branch of Korean traditional oriental
      medicine. Constitutions of Sasang medicine refer to Taeyangin, Taeumin, Soyangin,
      and Soumin. The differences of disease severity to be shown in the constitution
      may be due to genetic factors. Therefore, we examined interrelationship among
      cerebral infarction, CI, angiotensin converting enzyme (ACE) gene polymorphism,
      and Sasang constitutional classification. We investigated the association between
      ACE genotype and CI by case-control study in a Korean population. We also
      classified CI patients and control group into groups according to Sasang
      constitutional medicine. 208 CI patients and 643 controls without CI were
      examined. ACE genotype was determined by 7.5 % polyacrylamide gel separation
      after DNA amplification. The ACE/DD genotype was not associated with CI. The
      frequency of Taeumin of Sasang constitutional medicine in patients with CI was
      significantly higher than that in controls (chi2=41.202, p<0.001). However, the
      Taeumin constitution did not enhance the relative risk for CI in the subjects
      with ACE/DD genotype. Although we did not find any association between ACE gene
      polymorphism and CI in Koreans, there were significant differences in allele
      frequencies between Koreans and Europeans, but not Japanese and Chinese
      populations. Furthermore, we first attempted to evaluate the efficacy of Sasang
      constitutional medicine, and to find an association with CI.

PMID- 14641480
TI  - Mapping of quantitative trait loci controlling timing of bud flush in Salix.
AB  - Dormancy release is an important phenological stage, which determines plant
      growth and survival in northern temperate regions. Spring bud flushing was
      studied in a Salix pedigree (n=82) derived from a cross between the male hybrid
      clone "Bjorn" (Salix viminalis x Salix schwerinii) and the female clone "78183"
      (Salix viminalis). The timing of bud flush was recorded outdoors in two
      consecutive years (1998, 1999) and indoor in the spring of 1998. Timing of bud
      flush was found to be under moderately strong genetic control (clonal mean
      heritabilities ranging from 0.43 to 0.72). Phenotypic correlations between height
      growth and bud flushing were negative but non-significant (r=0.1-0.3). Using a
      Salix linkage map composed of 325 AFLP and 38 RFLP markers, six quantitative
      trait loci (QTLs) and three unmapped marker loci associated with timing of bud
      flush were detected. Four QTLs were detected in the field experiment while two
      QTLs and three unmapped marker loci were identified in the indoor experiment. One
      QTL associated with indoor bud flushing coincided with one of the QTL detected
      from the field data. Individual QTL explained 6-16% of the phenotypic variance
      [corrected]. None of the bud flush QTLs coincided with QTLs controlling height
      growth identified previously in the same pedigree.

PMID- 14641481
TI  - Influence of spatial structure on genetic isolation in Plebejus argus populations
      (Lepidoptera: Lycaenidae).
AB  - Populations of Plebejus argus were sampled in southwest Finland, both on the
      mainland and on islands, and in and around the Donana National Park in southwest
      Spain. A total of 453 individuals coming from 14 locations were investigated
      using allozyme electrophoresis on a total of 10 polymorphic allozyme loci.
      Contrary to earlier studies, all conducted in Britain, our samples showed little
      differentiation between sampled locations. In Spain, the populations of the
      Donana area showed no differentiation despite being up to 36 km apart; only the
      population to the south of the Guadalquivir river showed a significant difference
      to the others. In Finland the population on one island showed marked genetic
      differentiation from all the others, which showed little or no difference from
      each other. No isolation-by-distance effect could be detected in either system.
      We hypothesise that emigration-immigration events are more frequent in the
      Spanish and Finnish populations than in the British ones. We did, however, find
      two isolated populations, one in Spain and one in Finland; both were small and
      geographically isolated and shared evident drift.

PMID- 14641482
TI  - Transferability of microsatellite and sequence tagged site markers in Oryza
      species.
AB  - The genus Oryza comprises 22 species which are potentially useful as a source of
      genetic variability that can be introgressed into the worldwide cultivated rice,
      Oryza sativa. Molecular markers are useful tools for monitoring gene
      introgressions and for detecting polymorphism among species. In this study, cross
      amplification was estimated among 28 accessions of 16 Oryza species, representing
      the genomes AA, BB, CC, BBCC and CCDD, using 59 microsatellite (OG, OS and RM
      series) and 15 STS (Sequence Tagged Sites) markers. All markers amplified at
      least one Oryza species, indicating different levels of transferability across
      species. Markers based on microsatellite sequences amplified 37 % of the
      accessions, with an average of 6.58 alleles per locus and an average polymorphism
      information content (PIC) of 70 %. For STS markers, the amplification level was
      53.3 %, and the average number of alleles and PIC values were 1.6 and 10 %,
      respectively. These Results showed that although the STS markers detected a
      reduced level of genetic diversity, the transferability was higher, indicating
      that they can be used for genetic analysis when evaluating less genetically
      related species of Oryza. Among the microsatellite markers, an analysis of
      species with an AA genome showed that the OG markers produced the highest level
      of polymorphic loci (54.6 %), followed by RM markers (48 %). Highly polymorphic
      and transferable molecular markers in Oryza can be useful for exploiting the
      genetic resources of this genus, for detecting allelic variants in loci
      associated with important agronomic traits, and for monitoring alleles
      introgressed from wild relatives to cultivated rice.

PMID- 14641483
TI  - Quantitative variation of four morphological traits in Drosophila melanogaster
      under larval crowding.
AB  - Effects of three different larval densities (low, intermediate and high) on
      phenotypic and genetic variation of four morphological traits (thorax and wing
      length, sternopleural and abdominal bristle number) were studied in Drosophila
      melanogaster using the isofemale line technique. Phenotypic variation was found
      to increase at high larval density in all traits examined. Environmental variance
      for three traits (exception was sternopleural bristle number) and fluctuating
      asymmetry for both bilateral traits were also increased under high density
      conditions. For estimates of genetic variability (among isofemale lines variance,
      heritability and evolvability), no statistically significant differences among
      density regimes were detected. However, the trends in changes of these estimates
      across densities indicated a possibility for enhanced genetic variation under
      larval crowding for all traits except abdominal bristle number. For the latter
      trait, genetic variation seemed not to be dependent on density regime. Generally,
      two metric traits (thorax and wing length) were more affected by larval crowding
      than two meristic ones (sternopleural and abdominal bristle number). The Results
      are in complete agreement with those previously obtained for D. melanogaster
      using extreme temperatures as stress-factors.

PMID- 14641484
TI  - Karyotypic characterization of representatives from Melolonthinae (Coleoptera:
      Scarabaeidae): karyotypic analysis, banding and fluorescent in situ hybridization
      (FISH).
AB  - Meiotic chromosomes of Phyllophaga (Phytalus) vestita, Phyllophaga (Phyllophaga)
      aff capillata and Lyogenys fuscus (Melolonthinae) were analyzed by conventional
      staining, C-banding, fluorochromes, silver nitrate and FISH. The three species
      had a diploid number of 2n=20 and a sex mechanism of the (Xyp; XYp) parachute
      type. P. (Phytalus) vestita,P. (Phyllophaga) aff capillata and Lyogenys fuscus
      showed pericentromeric constitutive heterochromatin (CH) in all autosomal
      bivalents and on X chromosomes. Staining with CMA3 and DAPI fluorochromes showed
      that the CH of P. (Phytalus) vestita is not specifically rich in AT and GC-base
      pairs, whereas in P. (Phyllophaga) aff capillata the sex bivalent and one
      autosomal pair were found to be enriched in GC base pairs with CMA3, and in
      Lyogenys fuscus CH was positive for DAPI. Silver nitrate staining revealed
      nucleolar remnants in all three species. However, FISH obtained a precise
      identification of nucleolar organizing regions with an rDNA 18S and 25S probe. A
      signal of hybridization was seen in each species, being detected in the X
      chromosome of P. (Phytalus) vestita and Lyogenys fuscus, and in a small autosomal
      bivalent of P. (Phyllophaga) aff capillata.

PMID- 14641485
TI  - Ag-staining pattern, FISH and ISH with rDNA probes in the rice field eel
      (Monopterus albus Zuiew) chromosomes.
AB  - The present paper reports the Results of rice field eel (Monopterus albus Zuiew)
      chromosomal analysis by Ag-staining techniques, FISH and ISH with 18S rDNA. Both
      the Ag-NORs and the hybridization signals were observed on the pericentromeric
      region of chromosome pairs 3 and 7. The Ag-NORs and the hybridization signals on
      homologous chromosomes 3 and 7 were corresponding to each other. And rDNA genes
      were mapped to bivalents 3q12-q24 and 7q14-q26. No heteromorphic sex chromosome
      pair was identified. The Results obtained were discussed with respect to the
      feature of Ag-NORs and the position of rDNA genes on chromosome pairs 3 and 7.

PMID- 14641486
TI  - Chromosomal divergence and maintenance of sympatric Characidium fish species
      (Crenuchidae, Characidiinae).
AB  - Cytogenetic studies were performed in two syntopic species of Characidium, C.
      lauroi and Characidium sp. cf. C. alipioi, from Ribeirao Grande, Paraiba do Sul
      river basin. Both species have diploid number 2n=50 chromosomes, but differ in
      chromosome shape, C-banding pattern and location of nucleolar organizing regions.
      In Characidium sp. cf. C. alipioi a new type of ZW sex chromosome system composed
      of equal sized metacentric chromosomes is reported for the first time in the
      genus Characidium. Species of Characidium with a sex chromosome system form a
      monophyletic group. Variations in this system are interpreted as resulting from
      geographic isolation among allopatric species.

PMID- 14641487
TI  - Inheritance and diversity of simple sequence repeat (SSR) microsatellite markers
      in various families of Picea abies.
AB  - A large number of sequence-specific SSRs were screened by using electrophoresis
      on metaphore agarose gels with the bands visualized by ethidium bromide staining.
      Many SSRs appeared as codominant and many as dominant markers, with presence or
      absence of bands. A simple Mendelian inheritance pattern for most codominant and
      dominant SSR loci was found. For many codominant SSR markers, null alleles were
      detected. The proportion of dominant microsatellites detected in this study
      (close to 50 %) was much higher than that commonly reported in many other
      studies. A high proportion of dominant markers together with a high frequency of
      codominant markers with null alleles may represent two important limitations for
      the use of microsatellites in different studies. On the other hand, many
      polymorphic codominant SSR microsatellite markers were found to be highly
      repeatable, and can be used for population studies, seed certification, quality
      control of controlled crosses, paternity analysis, pollen contamination, and
      mapping of QTL in related families. In this paper, we report on the inheritance
      pattern and diversity of codominant and dominant SSR microsatellites in seven
      families of Picea abies sharing a common mother.

PMID- 14641488
TI  - Multivariate analysis of diversity of tef (Eragrostis tef (Zucc.) Trotter)
      germplasm from western and southern Ethiopia.
AB  - Sixty tef germplasm populations consisting of 3,000 panicle-derived lines from
      six western and southern regions of Ethiopia were evaluated for 17 pheno-morphic
      and agronomic traits on pellic Vertisols at Debre Zeit Agricultural Research
      Center during the 1999 main season. The objectives were to study the extent and
      pattern of variation of the germplasm with respect to regions and altitude zones,
      to classify the populations into relatively homogenous groups and to identify the
      major traits contributing to the overall diversity of the populations. At 75 %
      similarity level, the 60 populations aggregated into nine complexes of two to 10,
      with 12 populations remaining un-grouped. Five principal components (PC)
      extracted about 81 % of the gross variance among the populations. About 40 % of
      the variance accounted for by the first PC alone resulted largely from variations
      in diameters of the two basal culm internodes, grain yield and number of
      spikelets/panicle, shoot phytomass and grain yield/plant, and number of culm
      internodes. The entire regional as well as the clinal (altitude zone) variation
      was explained by five and two PCs, respectively. The discriminant analyses
      depicted about 77 % correct grouping of the 47 populations into nine clusters and
      about 62 % and 68 % correct origin-based classification of the germplasm in terms
      of altitude zones and regions, respectively. In general, the study demonstrated
      the existence of regional and clinal (altitude zone) variation patterns in the
      tef germplasm populations. The broad trait variation in the germplasm implies
      ample opportunities for genetic improvement of tef through selection and
      hybridization.

PMID- 14641489
TI  - Qualitative inheritance of water-stress induced apical sterility in wheat
      (Triticum aestivum).
AB  - Grain number per unit area is an effective component of grain yield in bread
      wheat. Water-stress induced apical sterility (tip sterility) reduces the number
      of grains and, consequently, the grain yield in semi-arid regions with a shortage
      of available water during the pre-anthesis period. Crosses between apical sterile
      and apical fertile varieties and selection lines were made and F1, BC1, and F2
      populations were subjected to moderate water-stress to study the inheritance of
      this character. The F2 and BC1 plants were qualitatively categorised into two
      phenotypes and tested for monohybrid and dihybrid segregation hypotheses. All the
      spikes of F1 plants obtained from crosses between apical fertile and apical
      sterile varieties were fully fertile indicating apical fertility is dominant to
      apical sterility. The F2 segregation Results from crosses between apical fertile
      lines and Y82187 suggested two complementary dominant genes segregating
      independently were involved in tolerance to water-stress induced apical
      sterility. In other words, two dominant genes determine apical fertility in these
      crosses and if one of these loci is homozygous, recessive waterstress will induce
      apical sterility. One F2 population segregated for both apical sterility and
      vernalisation response. Semi-winter plants had more sterile spikelets and the
      result of chi-square test confirmed monhybrid segregation for vernalisation
      response.

PMID- 14641490
TI  - Inversion polymorphism in Drosophila subobscura from two different habitats from
      the mountain of Goc.

PMID- 14641491
TI  - Innovation and diffusion in health library and information services.

PMID- 14641492
TI  - Evaluating digital libraries in the health sector. Part 1: measuring inputs and
      outputs.
AB  - This is the first part of a two-part paper which explores methods that can be
      used to evaluate digital libraries in the health sector. In this first part, some
      approaches to evaluation that have been proposed for mainstream digital
      information services are examined for their suitability to provide models for the
      health sector. The paper summarizes some major national and collaborative
      initiatives to develop measures for digital libraries, and analyses these
      approaches in terms of their relationship to traditional measures of library
      performance, which are focused on inputs and outputs, and their relevance to
      current debates among health information specialists. The second part* looks more
      specifically at evaluative models based on outcomes, and models being developed
      in the health sector.

PMID- 14641493
TI  - Access for all? A survey of health librarians in the north-west of England on
      provision of information to patients.
AB  - This study examined the role that health librarians could play in helping
      patients to find information. A questionnaire survey was sent out to 50 health
      librarians in the north-west of England. It examined the following: the type of
      library and users, access to information for patients, librarians' attitudes to
      provision of information to patients and their knowledge of other sources
      available to their users. Ninety-seven per cent of librarians said that they
      could recommend quality information sources to patients, but many suggested that
      there were practical problems in allowing patients to use health libraries due to
      lack of appropriate resources, facilities and funding. Advantages of health
      library involvement in patient information include having a local point of
      contact for patients and the ability of librarians to find, evaluate and organize
      good-quality resources. However, health library staff may not have enough time to
      answer enquiries from the public and may lack training in dealing with patients.
      Innovation, especially in developing on-line services, could offer a way to
      provide a service without overloading the physical requirements of a library.
      Librarians could also collaborate with other staff to improve patient
      information.

PMID- 14641494
TI  - Perceptions of the authority of health information. Case study: digital
      interactive television and the Internet.
AB  - As part of a Department of Health funded project nearly 2000 people were surveyed
      as to their use of two digital health information services, one on the Web and
      the other on digital interactive television (DiTV). The website was of a
      commercial company-Surgerydoor-and the DiTV service NHS based. This paper
      concentrates on the issue of trust in digital health information. Two of the main
      findings were that advertising was found to have an effect on trust, though the
      quality and type of advertising will impact in different ways on trustworthiness.
      DiTV subscribers who had either used the Living Health channel which carried NHS
      branded health information or had heard of the service, were more likely to say
      that the NHS was a symbol of trust for them compared with DiTV subscribers who
      had not used the service.

PMID- 14641495
TI  - Working together: supporting projects through action learning.
AB  - Recent years have seen tremendous growth in knowledge management projects within
      the NHS. Project staff must acquire rapidly a wide range of task-related skills.
      Conventional training courses may be inappropriately timed or unavailable to
      project staff. Action learning provides a group-based means of meeting skills
      deficits associated with project management and delivery. This paper describes an
      action learning set for project staff on five knowledge management projects
      within Trent Region. A brief evaluation aimed to identify most and least useful
      and most and least enjoyable features of the action learning set. Comments on the
      facilitation and the content of the action learning sessions are analysed. Action
      learning is feasible in meeting the training needs of project staff. It may also
      provide a means of meeting the shared learning needs of communities of practice
      within a virtual environment. Knowledge management does not merely involve
      management and delivery within innovative projects but also requires exploiting
      shared learning across projects.

PMID- 14641496
TI  - A recruitment and retention study of staff working in National Health Service
      libraries in the north-west of England.

PMID- 14641497
TI  - A pilot study on the use of inter-library loans by clinical staff.

PMID- 14641498
TI  - Using research in practice.

PMID- 14641499
TI  - Learning and teaching.

PMID- 14641503
TI  - CME in the European Journal of Neurology.

PMID- 14641504
TI  - Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in
      conditions affecting the cerebral vasculature.
AB  - Pathologic processes affecting the brain vessels may damage cerebral vasodilatory
      capacity. Early detection of cerebral dysfunction plays an important role in the
      prevention of cerebrovascular diseases. In recent decades acetazolamide (AZ) has
      frequently been used for this purpose. In the present work the mechanism of
      action and the previous studies are reviewed. The authors conclude that AZ tests
      are useful in cerebrovascular research. Further investigations are recommended to
      prove how impaired reserve capacity and reactivity influence the stroke risk in
      patients and whether these tests may indicate therapeutic interventions.

PMID- 14641505
TI  - Cost of a recurrent vs. cost of first-ever stroke over an 18-month period.
AB  - When assessing the cost-effectiveness of the secondary prevention of stroke, it
      is not well known whether the cost of a recurrent brain infarction (BI) is
      different from a first-ever BI. In a cohort of 435 consecutive prevalent cases of
      BI (including both recurrent and first-ever BI) we collected medical and socio
      economic variables. Handicap was measured with the Rankin scale. Only the direct
      medical costs were considered over an 18-month period from a societal
      perspective. We compared first-ever to recurrent BI. Of the 435 patients 20.5%
      had a recurrent BI. The length of the initial hospitalization and the
      distribution of the patients into the three classes of handicap (Rankin 0-2, 3,
      and 4-5) were similar in the first-ever and recurrent BI groups. The average
      total cost of a first-ever BI was euro 19 725 (95% CI, 17 950-21 501) and euro 18
      560 (95% CI, 15 798-21 322) for a recurrent BI (P = 0.48). There were no
      differences between the two groups when the costs were compared by handicap
      levels (P = 0.17) or when the costs were compared for each type of expenditure
      (initial hospitalization, rehabilitation, ambulatory services) except for long
      term care, because of the small number of cases. This study suggests that the
      costs of recurrent BI are roughly similar to the costs of first-ever BI, which
      may be helpful when studying the cost-effectiveness of secondary stroke
      prevention trials.

PMID- 14641506
TI  - MRI correlates of executive dysfunction in patients with ischaemic stroke.
AB  - Executive dysfunction (ED) may lead to problem behaviour and impaired activities
      of daily living in many neuropsychiatric disorders, but the neuroanatomical
      correlates of ED are still not well known. Different aspects of executive
      functions were studied by widely used neuropsychological tests in 214 elderly
      patients 3 months after ischaemic stroke, and a sum score of eight different
      measures was counted in each patient. The number and site of brain infarcts as
      well as severity and location of white matter lesions (WMLs) and brain atrophy on
      magnetic resonance imaging were recorded and compared between patients with and
      without ED. ED was present in 73 (34.1%) of the 214 patients. The mean frequency
      of brain infarcts in the brain and in the left hemisphere was higher in the
      patients with ED. Lesions affecting the frontal-subcortical circuits (e.g.
      pallidum, corona radiata or centrum semiovale) were more frequent in patients
      with ED than in those without. Also, patients with pontine brain infarcts
      frequently had ED, but this may have been due to more extensive ischaemic changes
      in these patients in general. Mean number of brain infarcts affecting the pons
      and posterior centrum semiovale on the left side, moderate to severe medial
      temporal atrophy, the Fazekas white matter score, the Mini-Mental State
      Examination score and low education were independent correlates of ED. Brain
      infarcts and WML affecting the frontal-subcortical circuits or the pons may
      increase risk for ED in stroke patients.

PMID- 14641507
TI  - Long-term safety and cognitive effects of galantamine in the treatment of
      probable vascular dementia or Alzheimer's disease with cerebrovascular disease.
AB  - The relationship between cholinergic dysfunction and cognitive and functional
      impairment in patients with vascular dementia (VaD) and Alzheimer's disease (AD)
      with cerebrovascular disease (CVD) suggests a potential role for cholinomimetic
      therapy. Initial studies of galantamine demonstrated cognitive, behavioral, and
      functional benefits in these populations. 326 patients with VaD or AD with CVD
      who completed an initial 12-month trial were treated with galantamine 24 mg/day
      in a 24-month, open-label extension. This interim analysis was performed at month
      12 of the open-label extension (248 completed the trial). Galantamine (up to 24
      months total) was well tolerated in both groups. The most frequently reported
      adverse events, characteristic of older dementia patients, included depression,
      agitation, and insomnia. Gastrointestinal adverse events were less common than
      initially, indicating declining incidence with long-term therapy. Patients taking
      galantamine for the entire study demonstrated the least cognitive decline on AD
      Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo
      initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of
      galantamine were evident in both groups; cognitive baseline levels were
      maintained for approximately 21 months in VaD patients and for 12 months in
      patients with AD with CVD. Long-term (up to 24 months) galantamine therapy in
      patients with VaD and AD with CVD is well tolerated and associated with prolonged
      maintenance of cognitive function.

PMID- 14641508
TI  - Ictal limb dystonia in temporal lobe epilepsy. an invasive video-EEG finding.
AB  - The aim of the investigation was to evaluate the ictal EEG in the putamen and the
      temporal and frontal lobes during contralateral ictal limb dystonia (ID). Ten
      epilepsy surgery candidates participated in the study. All of them were
      investigated using intracerebral and/or subdural electrodes. In four of the
      patients, the putamen was investigated with diagonal depth electrodes (patients 1
      4), in six of the patients, both the temporal and frontal lobes were investigated
      (patients 5-10). All of the investigated contacts were located contralateral to
      the side of the ictal dystonia. All of the patients suffered from temporal lobe
      epilepsy (TLE); in patient 10, both temporal and frontal seizure types were
      recorded. A total of 20 complex partial seizures (CPS) were analysed. ID was
      never an early symptom in the course of CPS. Slow activity was recorded in the
      putamen in all 10 seizures of the four patients in whom the putamen was
      investigated (patients 1-4). In five of these seizures, there was a time-locked
      change in the ictal EEG in relation to the ID (slowing of activity in three
      seizures; acceleration in two seizures). At the time of the onset of ID, several
      cortical regions were involved in the ictal discharge, within both the
      contralateral temporal and frontal lobes. In all 10 seizures of the six patients
      in whom both the temporal and frontal lobes on the contralateral side were
      evaluated (patients 5-10), the ictal paroxysmal discharge was noted in both lobes
      (i.e. frontal and temporal) at the time of ID onset. We can conclude that ID is a
      late symptom in TLE. Widespread activation of the contralateral temporal and
      frontal lobes is needed for the appearance of ID; however, the critical region
      responsible for the genesis of ID was not revealed. Although there are some non
      specific changes in the putamen contralateral to ID, the changes were never
      epileptic in type. The putamen probably collaborates in the genesis of ID, but it
      does not generate the epileptic discharge during its course.

PMID- 14641509
TI  - Anomia for people's names, a restricted form of transient epileptic amnesia.
AB  - A 37-year-old man consulted after two episodes of transient anomia for people's
      names over a period of 6 months. The first episode lasted about 10 min and was
      restricted to an inability to remember his 2-year-old son's first name. The
      second, was limited to an inability to recall his daughter's first name for 5 min
      with clear abnormal experiential quality. Witnessed descriptions of the attacks
      confirmed the absence of any other cognitive impairment or motor automatisms. The
      neurological examination was normal except for hyposmia. Inter-ictal cognitive
      evaluation was normal apart from the anomia for people's names or retrieval of
      names of familiar people in his childhood on definition and on famous faces
      naming test. A wake electroencephalograph showed left temporal epileptiform
      abnormalities, following hyperpnea. On magnetic resonance imaging, quantitative
      analysis revealed a mildly decreased volume of the left hippocampus. The
      diagnosis of transient epileptic amnesia (TEA) was considered and the patient did
      not recur for 6 months under lamotriginum. Thus anomia for people's names may be
      the sole clinical manifestation of TEA. Such a clinical presentation may easily
      be overlooked. Treatment may prevent further recurrence and the installation of
      more important and permanent autobiographical memory impairment. Our observation
      may suggest an isolated system not only for people's knowledge, but for people's
      naming. It is consistent with the notion of proper name as pure referring
      expression.

PMID- 14641510
TI  - Guillain-Barre syndrome in southern Taiwan: clinical features, prognostic factors
      and therapeutic outcomes.
AB  - To determine the clinical features, prognostic factors, and therapeutic results
      of Guillain-Barre syndrome (GBS) in order to improve the therapeutic strategy for
      this disease. We retrospectively reviewed the electrodiagnostic study and medical
      records of patients with GBS admitted to Chang Gung Memorial Hospital, Kaohsiung,
      between January 1986 and December 2000. Outcomes and prognosis were followed-up
      after 1 year. Ninety-six patients were enrolled in this study. According to the
      clinical and electrophysiological findings, 77 patients were acute inflammatory
      demyelinating polyradiculoneuropathy, seven were Miller Fisher syndrome, and six
      were axonal forms, and six were unclassified. At a follow-up of 1 year, 61
      patients (64%) recovered, 30 (31%) had residua and five (5%) died. Amongst these
      30 had residua, including unassisted gait in 19, assisted gait in four, and
      wheel/bed bound in seven. According to the statistical analysis, disabilities at
      the nadir (P < 0.0001) and at admission (P = 0.014) were significant prognostic
      factors. Variables used for the stepwise logistic regression, and the results
      revealed that after analysis for all the above variables, only disability at the
      nadir (P < 0.0001) was independently associated with the treatment failure rate.
      Our study revealed 27% of cases in need of respiratory support during
      hospitalization, and 5% of hospital-treated patients die from the complications.
      Furthermore, 31% had residua at a follow-up of 1 year or more. If prognostic
      factors are considered, disability at the nadir during hospitalization
      demonstrates consistently poor therapeutic outcomes. Therefore, early diagnosis,
      choice of appropriate treatment, and preventing complications during acute stages
      are essential to maximize the potential for survival.

PMID- 14641511
TI  - Volumetric quantitation by MRI in primary progressive multiple sclerosis: volumes
      of plaques and atrophy correlated with neurological disability.
AB  - In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic
      resonance imaging (MRI) differ from abnormalities in other subtypes of multiple
      sclerosis (MS). It was investigated whether the extent of brain and spinal cord
      MRI abnormalities is reflected in the neurological disability in PPMS. Focal and
      diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS
      (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI
      segmentation and volumetric analysis. The measurements were related to
      neurological disability as expressed by the expanded disability status scale
      (EDSS), the regional functional scoring system (RFSS), the arm index and the
      ambulation index. Plaques in T1- and/or T2-weighted images were seen in all
      brains, while spinal plaques were detected in 23 of 28 patients (82%). The total
      volumes of brain and spinal cord were significantly smaller in patients than in
      controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in
      the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P
      = 0.004, respectively). No correlations were detected between MRI measurements
      and total EDSS score, but relative brain atrophy correlated inversely with the
      total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P
      = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although
      the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P
      = 0.001), no correlations were found between EDSS subscores and spinal cord
      atrophy. These findings show that marked atrophy of brain and spinal cord
      detected by volumetric quantitation correlates with neurological disability. This
      observation indicates the importance of neurodegenerative events in PPMS.

PMID- 14641512
TI  - A retrospective, observational study comparing the four available
      immunomodulatory treatments for relapsing-remitting multiple sclerosis.
AB  - We performed an observational, retrospective analysis of outcome in a sequential
      cohort of patients with relapsing-remitting multiple sclerosis (RRMS) in
      Argentina. Patients treated for 16 months with interferon beta-1a (Avonex; 30
      micrograms intramuscularly, once a week), interferon beta-1a (Rebif); 44
      micrograms subcutaneously, thrice weekly), interferon beta-1b (Betaferon; 250
      micrograms subcutaneously, every other day) or glatiramer acetate (Copaxone; 20
      mg subcutaneously daily) were compared with a non-treated group of patients. The
      different treatment groups were similar in baseline demographic and clinical
      variables. A significant fall in the annual relapse rate was observed for all
      four treatments, with the largest effect observed with glatiramer acetate (81%
      reduction in relapse rate, compared with pre-treatment values). The proportion of
      patients remaining relapse-free for the entire 16-month treatment period varied
      from 37% in untreated patients to 83% in the glatiramer acetate treated group. No
      statistically significant changes in disability scores were observed over the
      treatment period. This first such comparative study in Latin America shows that
      treatment of multiple sclerosis patients with immunomodulatory therapies in the
      context of current standards of care in Argentina provides clinically important
      benefit, and suggest that some of these therapies may be better than others.

PMID- 14641513
TI  - Polyneuropathy associated with IgG/IgA monoclonal gammopathy: a clinical and
      electrophysiological study of 15 cases.
AB  - Peripheral neuropathy has been widely reported in patients with monoclonal
      gammopathy (MG), more frequently immunoglobulin M (IgM) or IgG than IgA.
      Nevertheless, it remains unclear whether this association has clinical or
      pathogenic relevance. In order to clarify the possible role of IgG/IgA MG in
      neuropathy, we studied the clinical and electrophysiological features of 15
      consecutive patients with polyneuropathy and IgG/IgA-MG, and compared them to
      those of 40 patients with polyneuropathy associated with IgM-MG, previously
      reported. Nine middle-aged patients (60%) had a chronic progressive or relapsing
      demyelinating polyneuropathy (DP) that was clinically and electrophysiologically
      indistinguishable from classic chronic inflammatory demyelinating polyneuropathy
      (CIDP) and frequently responded to immunosuppressive treatments, both
      characteristics supporting a dysimmune process. Six older patients (40%) had a
      chronic axonal distal polyneuropathy similar to the so-called chronic cryptogenic
      sensory polyneuropathy: there was no clear relationship with the MG in these
      patients and the response to immunosuppressive treatments was poor. Several
      features allowed us to distinguish between polyneuropathies associated with
      IgG/IgA-MG (IgG/IgA-PN) considered together and polyneuropathies associated with
      IgM-MG (IgM-PN). In the first group, the proportion of patients with a
      predominantly sensory clinical picture (27%) was less than that in the second
      group (75%), and there were fewer changes in nerve conduction studies. In
      addition, we found that the nine patients with DP associated with IgG/IgA-MG
      (IgG/IgA-DP) differed from the 31 with DP associated with IgM-MG (IgM-DP):
      clinical and electrophysiological studies clearly showed that the demyelinating
      pattern was more heterogeneous in IgG/IgA-DP than in IgM-DP. The spectrum of
      polyneuropathies associated with IgG/IgA-MG is heterogeneous, including DP, which
      is similar to classic CIDP, and axonal polyneuropathy, in which the pathogenic
      role of the MG remains elusive. In addition, IgG/IgA-DP differ from IgM-DP on
      clinical and electrophysiological grounds, suggesting probable different
      physiopathological mechanisms.

PMID- 14641514
TI  - Cost-utility analysis of intravenous immunoglobulin and prednisolone for chronic
      inflammatory demyelinating polyradiculoneuropathy.
AB  - The aim of this study was to provide an incremental cost-effectiveness analysis
      comparing intravenous immunoglobulin (IVIg) and prednisolone treatment for
      chronic inflammatory demyelinating polyradiculoneuropathy. Patients were
      recruited to a double-blind randomized crossover trial from nine European centres
      and received either prednisolone or IVIg during the first 6-week treatment period
      on which the economic evaluation was based. A societal perspective was adopted in
      measuring service use and costs, although the costs of lost employment were not
      included. The main outcome measure in the economic evaluation was the number of
      quality adjusted life years (QALYs) gained, with change in a 11-point disability
      scale used to measure clinical outcomes. Service use and quality of life data
      were available for 25 patients. Baseline costs were controlled for using a
      bootstrapped multiple regression model. The cost difference between the two
      treatments was estimated to be euro 3754 over the 6-week period. Health-related
      quality of life, as measured by the EuroQol EQ-5D instrument, increased more in
      the IVIg group but the difference was not statistically significant. Using a net
      benefit approach it was shown that the probability of IVIg being cost-effective
      in comparison with prednisolone was 0.5 or above (i.e. was more likely to be cost
      effective than cost-ineffective) only if one QALY was valued at over euro 250
      000. The cost-effectiveness of IVIg is greatly affected by the price of IVIg and
      the amount administered. The impact of later side-effects of prednisolone on long
      term costs and quality of life are likely to reduce the cost per QALY of IVIg
      treatment.

PMID- 14641515
TI  - Reduced jaw opening from paradoxical activity of mandibular elevator muscles
      treated with botulinum toxin.
AB  - The aim of the study was the effect of injections with botulinum toxin A (BTX-A)
      on reduced jaw opening, caused by paradoxical, antagonistic activity of jaw
      elevator muscles after brain stem lesions. The study included a male (51 years)
      and a female (69 years) patient. Subjective assessment, clinical recordings,
      muscle blocks and electromyography (EMG) were used to diagnose paradoxical
      activity, and to plan, guide and evaluate the treatment. The paradoxical
      innervation pattern was unilateral in the male and bilateral in the female. The
      paradoxical activity during jaw opening amounted to 24-109% of the level during
      maximum biting, and bursts of paradoxical activity were also present during
      chewing. EMG-guided blocks and later BTX-A injections of the affected muscles
      increased the opening by 9-23 mm from pre-treatment values of 15-18 mm, and
      normalized chewing. The study proved BTX-A to be an effective treatment for
      reduced jaw opening caused by paradoxical activity. Treatment was optimized by
      EMG evaluation of the current activity of the jaw elevator muscles, permitting
      individual treatment plans with longer intervals between BTX-A injections and
      lower doses than with conventional treatment for oromandibular dystonia. Thus the
      treatment only had to be repeated one to two times per year to maintain
      acceptable jaw mobility.

PMID- 14641516
TI  - Disease severity and outcome in thymoma myasthenia gravis: a long-term
      observation study.
AB  - Thymomas occurring in myasthenia gravis (MG) are usually of the cortical subtype
      and are usually treated by thymectomy. However, the factors that influence MG
      outcome in thymoma MG patients are not known. In a long-term study, MG severity
      and treatment was observed in 24 thymoma and 24 non-thymoma MG patients for up to
      30 years, and the occurrence of muscle autoantibodies was assayed. The rate of
      complete stable remission was low and did not differ between the two groups.
      There was no significant difference in MG severity between thymoma and non
      thymoma MG patients at any time during the study. Titin and ryanodine receptor
      (RyR) antibody occurrence was significantly higher in thymoma MG patients. Four
      thymoma (all titin and RyR antibody positive) and two non-thymoma (both titin and
      one RyR antibody positive) MG patients died from MG-related respiratory
      insufficiency. Seventy percent of thymoma and 75% of non-thymoma MG patients were
      treated with immunosuppressive drugs. The number of patients who received
      plasmapheresis did not differ in those who were treated because of acute MG
      deterioration, irrespective of planned surgery.This study shows equal MG severity
      and outcome in thymoma and non-thymoma MG, but the presence of RyR antibodies in
      thymoma MG and titin/RyR in non-thymoma MG indicates a less favorable prognosis.

PMID- 14641517
TI  - HLA class II genotypes in Mexican Mestizo patients with myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune, heterogeneous disorder, characterized by the
      presence of antibodies against acetylcholine receptors at the neuromuscular
      junction. There is a strong evidence that an individual's genetic composition is
      an important predisposing factor for the development of the disease. To correlate
      HLA class II genotypes with thymic pathology in Mexican Mestizo patients who had
      been subjected to thymectomy. HLA class II genes were analyzed in 60 patients and
      in 99 healthy ethnically matched controls. Thymic hyperplasia, atrophy, thymoma,
      and normal histology were encountered in 56, 33, 8 and 2% of patients,
      respectively. HLA-DR11 was significantly increased in patients with thymoma
      compared with healthy controls (pC = 0.001, OR = 13.35, 95% CI 3.5-51.3),
      compared with the subgroup of hyperplasia patients (pC = 0.005, OR = 15.5, 95% CI
      2.78-95.58) and with the atrophy subgroup (pC = 0.04, OR = 10.5, 95% CI 1.75
      70.95). This study provides the evidence of an association between HLA class II
      alleles with clinical and genetic heterogeneity in myasthenia gravis,
      particularly in those with thymoma (HLA-DR11).

PMID- 14641519
TI  - Cortical lesions associated with transient neurological symptoms - not always a
      matter of cause and effect.
AB  - The occurrence of transient recurrent stereotypical neurological events mandates
      the exclusion of an underlying brain lesion. When imaging studies demonstrate the
      presence of a structural brain lesion, a cause and effect relationship between
      the two entities is assumed, and the decision for surgical intervention may then
      follow almost automatically. We describe five patients with transient
      neurological events suspected as being seizures that were referred for surgery
      because of an associated structural brain lesion. Video electroencephalographic
      recordings revealed that the events that brought these patients to neurosurgical
      attention were non-epileptic seizures. None of these patients underwent surgical
      intervention, and all were referred for behavioral therapy. Therefore, even in
      the presence of a confirmed brain lesion, the presenting paroxysmal events may be
      of a non-organic origin and should not necessarily be assumed to be caused by the
      concomitantly existing structural abnormality.

PMID- 14641518
TI  - Human African trypanosomiasis: quantitative and qualitative assessment of
      intrathecal immune response.
AB  - Quantitative and qualitative techniques for assessment of the intrathecal humoral
      immune response in human African trypanosomiasis were compared, and their
      diagnostic potential for detection of the meningo-encephalitic stage of the
      disease was evaluated. Total and trypanosome specific immunoglobulin G (IgG) and
      IgM intrathecal synthesis were studied in paired cerebrospinal fluid (CSF) and
      blood samples of 38 trypanosomiasis patients and in three controls using Reiber's
      formulae. The presence of CSF-specific oligoclonal IgG and of trypanosome
      specific antibodies was determined using iso-electric focusing followed by
      immunoblotting and antigen-driven immunoblots. The intrathecal IgG fraction (16%
      positive) and oligoclonal IgG detection (24% positive) were insensitive for
      detection of an intrathecal humoral immune response. Trypanosome-specific IgG
      synthesis, reflected by the IgG antibody index (AI) (26% positive), was confirmed
      by the presence of oligoclonal specific IgG (47% positive), but the latter was
      more sensitive. Although the detection technique failed for oligoclonal IgM, the
      intrathecal IgM fraction (42% positive) and the IgM AI (32% positive) indicated
      that the meningo-encephalitic stage of the disease is characterized by a dominant
      intrathecal IgM response, which was higher than the IgG response. The highest
      combination of diagnostic sensitivity and specificity for the meningo
      encephalitic stage of trypanosomiasis was observed for quantitative IgM
      determinations.

PMID- 14641520
TI  - Jaw-opening dystonia (Brueghel's syndrome) associated with cavum septi pellucidi
      and Verga's ventricle - a case report.
AB  - Jaw-opening dystonia (oromandibular dystonia with jaw-opening; Brueghel's
      syndrome) is a rare condition, and only a limited number of cases have been
      reported in the literature. However, many patients may remain undiscovered or
      misdiagnosed, like a patient described previously. A case (40-year-old man) of
      jaw-opening dystonia (oromandibular dystonia with jaw-opening; Brueghel's
      syndrome) is reported. In this case, brain anomalies, cavum septi pellucidi and
      Verga's ventricle, were observed on magnetic resonance imaging of the brain. This
      case and a review of the literature indicate the presence of organic factors in
      the etiology of Brueghel's syndrome. The etiological relationship of brain
      anomalies in Bruegel's syndrome is discussed.

PMID- 14641521
TI  - Left internal carotid artery dissection presenting with headache, Collet-Sicard
      syndrome and sustained hypertension.
AB  - The baroreflex maintains blood pressure through the glossopharyngeal (IX) cranial
      nerve. We report a 54-year-old man who developed a left sided headache,
      hoarseness, dysarthria, dysphagia, and sustained hypertension from a left
      internal carotid artery dissection. We hypothesise that interruption of the left
      IX nerve caused hypertension in this patient.

PMID- 14641522
TI  - Results of carpal tunnel release.
AB  - We evaluated, by means of a prospective study, the results of carpal tunnel
      release both clinically and electrophysiologically in 188 patients with a carpal
      tunnel syndrome. A questionnaire was completed by patient and surgeon pre- and
      post-operatively (6 and 12 months after operation), when physical examination,
      electromyography and nerve conduction tests were also performed. Full pre- and
      post-operative results were available for 136 patients and 82% of the patients
      were satisfied with the results of the operation. Symptoms caused by median nerve
      compression showed the greatest improvement and no fixed patterns with regard to
      unsatisfactory results were found. If pain persisted in the wrist, many patients
      considered the operation to have been unsuccessful. Electrophysiological
      improvement occurred in all patients and at 12 months follow-up, median nerve
      conduction was normal in 21% of cases. Thus distal sensory latency remained
      abnormal in 79% of the patients, emphasizing the need for caution when recurrence
      of carpal tunnel syndrome is diagnosed in such cases.

PMID- 14641523
TI  - A C77G point mutation in CD45 exon 4, which is associated with the development of
      multiple sclerosis and increased susceptibility to HIV-1 infection, is
      undetectable in Japanese population.
AB  - HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one
      outcome of Human T-cell lymphotropic virus type 1 (HTLV-1) infection. It remains
      unknown why the majority of infected people remain healthy whereas only
      approximately 2-3% develop disease. Recently, heterozygous state of CD45 exon 4
      mutation (C77C wild type and C77G mutant) was reported to be associated with
      development of multiple sclerosis in German patients and increased susceptibility
      to HIV-1 infection in the United Kingdom. To investigate whether this mutation is
      associated with the development of HAM/TSP, we studied a group of 164 HAM/TSP
      patients and 108 asymptomatic HTLV-1 carriers in Kagoshima (HTLV-1 endemic area
      in Southern Japan) by using PCR-RFLP and subsequent direct sequencing analysis.
      All 272 subjects showed homozygosity in the CD45 exon 4, suggesting that this
      mutation is absent or very rare in Japanese population.

PMID- 14641524
TI  - Multiple progressive intracerebral hemorrhages due to an angiosarcoma: a case
      report.
AB  - Identification of intracerebral hemorrhage (ICH) and the underlying cause is a
      common clinical problem. Rare causes of ICH can be particularly difficult to
      diagnose. We describe a man on oral anticoagulation with multiple progressive
      ICHs, who initially showed no signs of a malignant disease. After normalisation
      of all coagulation tests, the ICHs continued to spread. Autopsy examination
      revealed an angiosarcoma. Multiple progressive ICHs caused by an angiosarcoma
      that mainly affects the brain have not yet been described. In the presence of
      normal coagulation tests, further progression of ICH should raise questions about
      common causes of ICH such as oral anticoagulation in our case.

PMID- 14641525
TI  - Choreoathetosis related to lithium intoxication.
AB  - A 76-year old woman was admitted because of severe gait ataxia and dysarthric
      speech that had worsened over the last 24 h. The patient was initially suspected
      of having repeated transitory ischemic attacks (TIAs) as her daughter reported a
      similar episode that had happened 3 weeks prior to admission. The onset of
      spontaneous twisting, choreoathetotic movements of both hands and arms and
      worsening of symptoms one hour after admission together with a history of lithium
      therapy lead to the correct diagnosis and appropriate treatment.

PMID- 14641526
TI  - Neurological findings in a case of coma secondary to Datura stramonium poisoning.

PMID- 14641527
TI  - Headache and musculoskeletal symptoms.

PMID- 14641529
TI  - Hashimoto's encephalopathy: a treatable cause of mental impairment, stroke and
      seizures.

PMID- 14641530
TI  - Intrathecal antibody production against Borrelia burgdorferi in a patient with
      relapsing-remitting multiple sclerosis.

PMID- 14641531
TI  - SIADH and seizure associated with immunoglobulin therapy.

PMID- 14641538
TI  - The CD36 protein functions as an immunogenic domain of the RT8 alloantigen.
AB  - Completely concordant distributions of Cd36 and Rt8 deletion/null and wild-type
      alleles among inbred and congenic strains, together with Western blot analysis of
      RT8/CD36 proteins, indicated that the CD36 protein functions as an immunogenic
      domain of the RT8 alloantigen.

PMID- 14641539
TI  - The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region:
      no association with inflammatory bowel disease.
AB  - Genetic predisposition has been suggested to play an important role in the
      pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have
      identified a Crohn's disease susceptibility locus on chromosome 14 (14q11-12;
      IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that
      has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5
      and IL-13. The IL-25 gene is located within this susceptibility region at
      14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine
      response, we hypothesized that genetic alterations within the IL-25 gene might
      contribute to IBD. First, direct sequencing of the coding regions of the IL-25
      gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a
      newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this
      polymorphism was further investigated in 151 patients with Crohn's disease, 111
      patients with ulcerative colitis, and 119 healthy controls to determine its
      clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any
      significant differences between patients with Crohn's disease or ulcerative
      colitis and controls. Genoytype-phenotype relations in patients with Crohn's
      disease showed a comparable distribution of the c424C/A polymorphism in all
      subgroups of the Vienna classification. In summary, our data indicate that
      genetic alterations in the coding regions of the IL-25 gene are unlikely to play
      a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be
      investigated for a potential association with other chronic inflammatory and
      inherited disorders such as autoimmune diseases.

PMID- 14641540
TI  - Rapid denaturing high-performance liquid chromatography (DHPLC) for mutation
      scanning of the transforming growth factor beta3 gene using a novel proof-reading
      polymerase.
AB  - We have utilized a novel variation on the conventional denaturing high
      performance liquid chromatography (DHPLC) technology, which we term rapid DHPLC,
      combining changes in instrumentation, cartridge technology and analysis
      conditions to enable significant increases in throughput to be achieved. In
      addition, the use of a novel proof-reading polymerase for sample amplification
      with a low misincorporation rate enables simplification of the DHPLC patterns and
      hence enhanced mutation detection recognition. This scheme for increasing DHPLC
      throughput has been tested by scanning the transforming growth factor (TGF) beta3
      gene for the presence of mutations for which there is limited published or on
      line data available regarding the presence of gene polymorphisms. TGFbeta
      isoforms have multiple roles in cell division, growth, proliferation,
      transformation and differentiation. TGFbeta3 is a TGFbeta cytokine isoform, and
      has an important role in embryogenesis, cell differentiation and wound healing.
      The TGFbeta3 gene consists of seven exons and six introns spanning 43 000 bp of
      the human genome on chromosome 14q23-24. The rapid DHPLC approach enabled
      scanning of all seven exons and part of the promoter region (1000 bp upstream
      from exon 1 in the 5'-flanking regions) of the TGFbeta3 gene in 95 Caucasian
      individuals in only 8 days, in comparison to the 17 days it would have previously
      taken. Mutations were clearly identified in the promoter region of the TGFbeta3
      gene but were absent from the exonic regions. Understanding the genetic
      variations affecting the TGFbeta3 gene is important as this molecule has multiple
      regulatory functions on a variety of cell types.

PMID- 14641541
TI  - Cytokine polymorphism frequencies in the Greek Cypriot population.
AB  - There is considerable evidence to suggest that several cytokine genes are
      polymorphic, resulting in differential transcription and protein expression
      levels among individuals. It has also been demonstrated that ethnicity can be a
      determinant for distinctive cytokine polymorphism frequencies. In this study, we
      evaluated the distribution of cytokine gene polymorphisms in 100 healthy Greek
      Cypriot subjects, using polymerase chain reaction-sequence-specific primers (PCR
      SSP) typing analysis. Cytokine gene polymorphisms were determined for
      transforming growth factor (TGF) beta1 codon 10 (TGFbetac10; C to T), TGFbeta1
      codon 25 (TGFbetac25; G to C), tumour necrosis factor alpha (TNFalpha) promoter 
      308 (G to A), interleukin (IL)-6 promoter -174 (G to C), IL-10 promoter -1082 (G
      to A), IL-10 promoter -819 (C to T), IL-10 promoter -592 (C to A) and interferon
      gamma (IFNgamma) intron 1 +874 (A to T). Frequencies for the above cytokine
      genotypes were calculated for the Greek Cypriot population.

PMID- 14641542
TI  - Promoter polymorphisms of the CD14 gene are not associated with bronchial asthma
      in Caucasian children.
AB  - Several studies have investigated the association of a promoter polymorphism in
      CD14 with atopic phenotypes. We screened this and another polymorphism in 182
      asthmatic children and found no association with asthma. Furthermore, there was
      substantial linkage disequilibrium of the polymorphisms. Thus CD14 does not play
      a major role in the development of asthma in our population of Caucasian
      children.

PMID- 14641543
TI  - No linkage or association of five polymorphisms in the interleukin-4 receptor
      alpha gene with atopic asthma in Italian families.
AB  - The literature contains conflicting reports on the association of common variants
      of the interleukin (IL)-4 receptor alpha (IL4RA) gene with atopic asthma. The
      purpose of the present study was to investigate the linkage and association of
      several gene polymorphisms with atopic asthma in a large series of well
      characterized individuals. Analysis of five polymorphisms (I50V, E375A, C406R,
      S478P and Q551R) of the IL4RA gene was performed in 823 individuals from 182
      families with atopic asthmatic children from north-east Italy. The subjects were
      tested for clinical asthma, total serum IgE level, skin prick test positivity to
      common aeroallergens, and bronchial hyperresponsiveness to methacholine. The
      frequency of the polymorphisms was similar to that reported for other
      populations. The 375, 406, 478 and 551 polymorphisms were in linkage
      disequilibrium, as previously reported. No linkage or transmission disequilibrium
      was observed in the families between any mutation and any of the phenotypes
      investigated. No multipoint haplotype was associated with any phenotype. In
      conclusion, the IL4RA gene does not seem to play an important role in genetic
      predisposition to atopic asthma in the population tested.

PMID- 14641544
TI  - Association between an interleukin-13 promoter polymorphism and atopy.
AB  - Several studies indicate genetic involvement of Th2 cytokines in allergic
      diseases. Interleukin (IL)-13 has been mapped to the cytokine cluster on
      chromosome 5q31-33, which has been associated with atopic conditions. Recently,
      an association was reported between the T allele in a promoter polymorphism in
      the IL-13 gene (C to T exchange) at position -1055 and allergic asthma in a
      population study in the Netherlands. This observation was apparently confirmed in
      a case-control study using probands and spouses from a Dutch asthma family study,
      but the polymorphism in that study was reported to occur at position -1111. In
      the present study, we established that this polymorphism is located at position 
      1024 relative to the ATG translation initiation codon, and investigated whether
      it confers a genetic predisposition to atopic conditions and the Th1 condition
      multiple sclerosis (MS) in Caucasian subjects. We confirmed the association
      between the IL-13 -1024TT genoype and inhalation allergy (P = 2.4E-02). By
      combining the data from the three studies, we demonstrated a strong association
      (P = 1.09E-05) between the IL-13 -1024 marker and inhalation allergy.
      Furthermore, we showed for the first time that this association also exists in
      atopic dermatitis (P = 2.0E-02). No association with MS was found.

PMID- 14641545
TI  - Geographic patterns of functional categories of HLA-DRB1 alleles: a new approach
      to analyse associations between HLA-DRB1 and disease.
AB  - Because specific amino acids found within the peptide-binding cleft of human
      leukocyte antigen (HLA) molecules have been implicated in HLA/disease
      associations, an approach which consists in grouping the alleles according to
      their functional properties at the protein level may enable us to better
      understand HLA associations than the conventional allelic classification. In this
      study, we applied this methodology to investigate the associations between HLA
      DRB1 and rheumatoid arthritis. The alleles were first classified into seven
      functional categories [restrictive supertype patterns (RSPs)], among which three
      were known to be significantly associated with susceptibility (one category) or
      resistance (two categories) to rheumatoid arthritis. The frequencies of these
      categories were then estimated in 104 population samples previously tested for
      HLA-DRB1, and their variability was analysed spatially on a worldwide scale by
      applying an original methodology for detecting discontinuities in geographically
      patterned data. RSP frequencies were also compared to known values of rheumatoid
      arthritis prevalence in some populations. The results indicated that the three
      RSP frequency distributions were geographically structured, and that these
      patterns could generally be explained by the history of human migrations.
      However, the peculiar pattern observed for RSP 'A' (conferring susceptibility to
      rheumatoid arthritis) indicated a possible association with some latitude
      dependent disease. Furthermore, the very high correlation coefficient found
      between RSP 'A' frequencies and rheumatoid arthritis prevalence confirmed the
      significant disease association of this functional category. In contrast, the
      putative protective effect of the other RSPs ('De' and 'Q') was not detectable at
      the worldwide level, but may be significant in specific geographic areas. This
      study shows that population genetic diversity analyses based on a functional
      grouping of HLA alleles provide an efficient way to explore the mutual influence
      of HLA genetic variation and disease.

PMID- 14641546
TI  - Analysis of Fc gamma receptor II (CD32) polymorphism in populations of African
      and South Asian ancestry reveals east-west geographic gradients of allele
      frequencies.
AB  - Analysis of FcgammaRIIA alleles in Pakistanis and in Trinidadians of South Asian,
      African and mixed ancestry revealed no significant differences between
      Trinidadian South Asians and Pakistanis. H131 homozygotes were more common among
      Trinidadian South Asians than among Africans and those of mixed ancestry.
      Comparison with other populations revealed east-west geographic gradients of
      allele frequencies.

PMID- 14641547
TI  - Nomenclature for factors of the HLA system, update July 2003.

PMID- 14641548
TI  - Nomenclature for factors of the HLA system, update August 2003.

PMID- 14641549
TI  - Organic anion-transporting polypeptide (OATP) transporter family and drug
      disposition.
AB  - Drug transporters are increasingly recognized as a key determinant of drug
      disposition. Recent studies have revealed that targeted expression of drug uptake
      and efflux transporters to specific cell membrane domains allows for the
      efficient directional movement of many drugs in clinical use. While the role of
      certain efflux transporters such as MDR1 (P-glycoprotein) in drug disposition has
      been extensively studied, emerging evidence suggests that uptake transporters may
      also be important to the intestinal absorption and renal or hepatic elimination
      of drugs. Members of the organic anion-transporting polypeptide (OATP) family of
      drug uptake transporters have been found capable of transporting a large array of
      structurally divergent drugs. Moreover, expression of OATP isoforms in the
      gastrointestinal tract, liver and kidney, as well as at the level of the blood
      brain barrier, has important implications for our understanding of the factors
      governing drug absorption, elimination and tissue penetration.

PMID- 14641550
TI  - Importance of P-glycoprotein for drug disposition in humans.
AB  - The ATP-binding cassette transporter P-glycoprotein is now recognized as an
      important determinant for disposition of multiple drugs. The use of P
      glycoprotein-expressing cell lines, the generation of P-glycoprotein knockout
      mice as well as studies in animals and humans contributed to a better
      understanding on the role of active transport processes for drug disposition. P
      glycoprotein is located in tissues with excretory function such as intestine,
      liver and kidney. Moreover, due to its expression in important blood-tissue
      barriers (blood-brain and blood-testis barriers), in lymphocytes and in placenta
      it limits tissue penetration of its substrates. Induction and inhibition of P
      glycoprotein have now been identified as important underlying mechanisms of drug
      interactions in humans. Using selected examples, this review summarizes currently
      available data on the impact of P-glycoprotein for bioavailability of drugs, drug
      interactions and drug effects.

PMID- 14641551
TI  - The effects of fruit juices on drug disposition: a new model for drug
      interactions.
AB  - Grapefruit juice produces mechanism-based inhibition of intestinal drug
      metabolism when consumed in normal quantities. This can produce clinically
      important increases in oral drug bioavailability when coadministered with
      substrates of cytochrome p450 3A4 (CYP3A4) that undergo high presystemic
      metabolism. Furanocoumarins such as bergamottin and 6',7'-dihydroxybergamottin
      have been identified as probable active constituents. Grapefruit juice may also
      inhibit intestinal P-glycoprotein-mediated efflux transport of drugs such as
      cyclosporine to increase its oral bioavailability. However, grapefruit juice does
      not enhance the absorption of digoxin, a prototypical P-glycoprotein substrate,
      likely because it has high inherent oral bioavailability. Grapefruit and other
      fruit juices have recently been shown to be potent in vitro inhibitors of a
      number of organic anion-transporting polypeptides (OATPs). These juices were also
      found to decrease the absorption of the nonmetabolized OATP substrate,
      fexofenadine. Taken together, the data support inhibition of intestinal uptake
      transporters by fruit juices to decrease drug bioavailability. This would
      represent a new mechanism for food-drug interactions. These findings with
      grapefruit and other fruit juices continue to enhance our understanding of the
      complex nature of food-drug interactions, and their possible influence on the
      clinical effects of medications.

PMID- 14641552
TI  - Pharmacogenetics of cytochrome p4502D6: genetic background and clinical
      implication.
AB  - Interindividual differences in the pharmacokinetics of a number of drugs are
      often due to hereditary polymorphisms of drug-metabolizing enzymes. Most
      important is cytochrome p4502D6 (CYP2D6), also known as debrisoquine/sparteine
      hydroxylase. It catalyzes hydroxylation or demethylation of more than 20% of
      drugs metabolized in the human liver, such as neuroleptics, antidepressants, some
      beta-blockers and many others like codeine. About 7%-10% of Caucasians lack any
      CYP2D6 activity due to deletions and frame-shift or splice-site mutations of the
      gene. About 1%-3% of Middle-Europeans, but up to 29% of Ethiopians display gene
      duplications, leading to elevated so-called ultrarapid metabolization rates.
      Meanwhile there is now a much better understanding of the genetic background of
      poor, intermediate, extensive and ultrarapid metabolizers, enabling a more
      precise DNA genotyping-based prediction of plasma levels. Since there is evidence
      that deteriorated drug elimination partly accounts for drug side-effects, CYP2D6
      genotyping could contribute to an individualized and therefore optimized drug
      therapy.

PMID- 14641553
TI  - Clinical relevance of genetic polymorphisms in the human CYP2C9 gene.
AB  - Cytochrome p450 (CYP) 2C9 hydroxylates about 16% of drugs in current clinical
      use. Of special interest are those with a narrow therapeutic index, such as S
      warfarin, tolbutamide and phenytoin, where impairment in CYP2C9 metabolic
      activity might cause difficulties in dose adjustment as well as toxicity. Single
      nucleotide polymorphisms (SNP) in the CYP2C9 gene have increasingly been
      recognized as determinants of the metabolic phenotype that underlies
      interindividual and ethnic differences. Apart from the wild-type protein CYP2C9*1
      at least five allelic variants produce allozymes with reduced or deficient
      metabolic activity. Among white populations only CYP2C9*2 and CYP2C9*3 variants
      are of significance, with allelic frequencies of 0.08-0.14 and 0.04-0.16,
      respectively. In contrast, in Africans (African-Americans and Ethiopians) and
      Asians both variants are much less frequent (0.005-0.04), and CYP2C9*2 has not
      yet been detected in Asians. CYP2C9*4 has been exclusively identified in Japanese
      patients, and CYP2C9*5 and *6 were only found among African-Americans with a low
      allelic frequency of 0.017 and 0.006, respectively. Furthermore in Japanese a
      CYP2C9 promotor variant of four linked SNPs was correlated with reduced intrinsic
      clearance of phenytoin in vitro. Subjects who are carriers of one or more variant
      alleles may be at risk for adverse drug reactions/toxicities when prescribed
      drugs extensively metabolized by CYP2C9.

PMID- 14641555
TI  - Crosslinks in Neurophysiology and Epilepsy: A Symposium in Honour of Fernando H.
      Lopes da Silva. Noordwijk, The Netherlands, September 29, 2000.

PMID- 14641556
TI  - Induced oscillations in the alpha band: functional meaning.
AB  - The phenomena of event-related desynchronization (ERD) and synchronization (ERS)
      reflect the dynamics of neural networks and can be observed on different scalp
      locations at the same moment of time. Whereas on one cortical area a focal 10-Hz
      ERD can be found, other areas can display a 10-Hz ERS. This phenomenon is called
      focal ERD/surround ERS and is interpreted as a correlate of an activated cortical
      area (ERD) and simultaneously deactivated or inhibited other areas. The induced
      oscillations (ERS) are dominant in the 10- to 13-Hz band and very likely mediated
      by thalamic gating.

PMID- 14641558
TI  - Noninvasive methods for evaluating the localization and propagation of epileptic
      activity.
AB  - There are multiple approaches to analyzing the scalp EEG to obtain information on
      the intracerebral generators of epileptic activity. We review here a few of these
      methods, as they have been applied in various research projects carried out at
      the Montreal Neurological Institute. The areas covered include the validation of
      dipole models of epileptic spikes and of seizure discharges, the EEG microscope
      of Kobayashi, the analysis of rapid spread of epileptic seizures, and the
      recently developed method of combining EEG and functional magnetic resonance
      imaging to obtain activation regions at the time of spikes.

PMID- 14641557
TI  - Sleep oscillations developing into seizures in corticothalamic systems.
AB  - PURPOSE: The aim of this article is to discuss the neuronal substrates of sleep
      oscillations leading to seizures consisting of spike-wave (SW) complexes at 2-4
      Hz, mimicking those seen in absence epilepsy, or SW and polyspike-wave (PSW)
      complexes at 1.5-2.5 Hz, often associated with fast runs at 10-15 Hz, as in the
      Lennox-Gastaut syndrome. METHODS: Extracellular recordings were done in
      permanently implanted animals during the natural waking-sleep cycle. Single and
      dual simultaneous recordings from cortical neurons, cortical and thalamic
      neurons, or cortical neurons and glial cells were performed in cats under
      ketamine-xylazine anesthesia. RESULTS: (a) The minimal substrate of SW seizures
      is the neocortex because such seizures may occur in thalamectomized animals, in
      which spindles are absent. In intact-brain animals, SW seizures are initiated in
      neocortex and spread to the thalamus after a few seconds. The majority of
      thalamocortical (TC) neurons are steadily hyperpolarized throughout the cortical
      SW seizures. (b) In the Lennox-Gastaut syndrome, the paroxysmal depolarizing
      shifts (PDSs) associated with the EEG "spike" of SW/PSW complexes contain an
      important inhibitory component, whereas the hyperpolarization during the EEG
      "wave" component is not due to gamma-aminobutryic acid (GABA)ergic inhibitory
      postsynaptic potentials (IPSPs) but is ascribed to a mixture of disfacilitation
      and K+ currents. As is also the case with seizures consisting of pure SW
      complexes, the majority of TC neurons are hyperpolarized during the cortical
      paroxysms and disinhibited after the cessation of cortical seizures. CONCLUSIONS:
      Seizures with SW complexes and of the Lennox-Gastaut type preferentially evolve
      from sleep oscillations. They are initiated in neocortex and spread to the
      thalamus after a few seconds. The majority of TC neurons are inhibited during
      these seizures.

PMID- 14641559
TI  - Toward a neurodynamical understanding of ictogenesis.
AB  - Although considerable information on cellular and network mechanisms of epilepsy
      exists, it is still not understood why, how, and when the transition from
      interictal to ictal state takes place. The authors review their work on nonlinear
      EEG analysis and provide consistent evidences that dynamical changes in the
      neural activity allows the characterization of a preictal state several minutes
      before seizure onset. This new neurodynamical approach of ictogenesis opens new
      perspectives for studying the basic mechanisms in epilepsy as well as for
      possible therapeutic interventions.

PMID- 14641560
TI  - Models and mechanisms of experimental epilepsies.
AB  - PURPOSE: To review the value of experimental models of epilepsy to help us
      understand the underlying basic neuronal mechanisms. METHODS: The methods
      addressed here include a variety of acute and chronic experimental epilepsies and
      their investigation in vitro, in vivo, and in computer simulations. RESULTS:
      Epileptic discharges are emergent properties of neuronal networks, depending
      crucially on intrinsic neuronal properties, and on the structural and functional
      organisation of the synaptic networks that interconnect them. Fast oscillations
      are another emergent property of these networks; while they are involved in
      normal function, they can play a crucial role in the initiation of at least some
      kinds of focal seizure. DISCUSSION: Brief "interictal" epileptic events are now
      relatively well understood. Rather less so are the mechanisms of chronic
      epileptic foci, and particularly of the prolonged hypersynchronous
      hyperexcitability characteristic of focal seizures, but here too progress is
      being made, offering the prospect of better targeted treatments.

PMID- 14641561
TI  - Temporal lobe epileptogenesis and epilepsy in the developing brain: bridging the
      gap between the laboratory and the clinic. Progression, but in what direction?
AB  - The origins of human mesial temporal lobe epilepsy and hippocampal sclerosis are
      still not well understood. Hippocampal sclerosis and temporal lobe
      epileptogenesis involve a series of pathologies including hippocampal neuronal
      loss and gliosis, axonal reorganization, and maybe hippocampal neoneurogenesis.
      However, the causality of these events is unclear as well as their relation to
      the factors that may precipitate epileptogenesis. Significant differences between
      temporal lobe epileptogenesis in the adult and immature brain may require
      differential approaches. Hereditary factors also may participate in some cases of
      hippocampal sclerosis. The key point is to identify the significance of these age
      dependent changes and to design preventive treatments. Novel strategies for the
      prevention and treatment of mesial temporal lobe epilepsy and hippocampal
      sclerosis may include rational use of neuroprotective agents, hormonotherapy,
      immunizations, and immunotherapy.

PMID- 14641562
TI  - Advances in understanding the process of epileptogenesis based on patient
      material: what can the patient tell us?
AB  - Many different types of epileptic seizures and epileptic syndromes exist. The
      process of epileptogenesis and the progressive nature of epilepsy, however, can
      most easily be investigated in the acquired epilepsies, in which a brain insult
      presumably gives rise to changes in neuronal systems that ultimately become
      capable of generating spontaneous ictal events. Invasive in vivo and in vitro
      research can be carried out in patients with acquired epileptogenic lesions in
      the course of epilepsy surgery; however, such studies are possible only for those
      epileptic conditions that can be treated surgically, and can be used only to
      examine an end stage of the epileptogenic process. Consequently, experimental
      animal models of human epileptic conditions are still required to study
      mechanisms by which specific cerebral insults initiate the epileptogenic process
      and the progression of an epileptic disturbance. Most current parallel
      human/animal invasive research has been focused on temporal lobe epilepsy, and
      particularly that form associated with hippocampal sclerosis, the most common
      human epileptogenic lesion. Studies indicate that epileptogenesis in this
      condition is initiated by specific types of cell loss and neuronal
      reorganization, which results not only in enhanced excitation, but also in
      enhanced inhibition, predisposing to hypersynchronization. Even within this
      single, well-studied epileptic disorder, evidence is found for more than one type
      of ictal onset, and individual seizures can demonstrate a transition from one
      ictal mechanism to another. Recent in vivo and in vitro parallel, reiterative
      investigations in patients with mesial temporal lobe epilepsy, and in rats with
      intrahippocampal kainate-induced hippocampal seizures, have revealed the presence
      of interictal epileptiform events, termed "fast ripples," which appear to be
      unique in tissue capable of generating spontaneous seizures. Pursuit of the
      fundamental mechanisms underlying these abnormalities should elucidate the
      neurobiologic basis of epileptogenicity in this disorder. Furthermore, if these
      events are markers for epileptogenicity, they may have clinical value for
      diagnosis and pharmacologic, as well as surgical, treatment. Further research is
      needed to determine if these observations are relevant to other types of
      epilepsies.

PMID- 14641563
TI  - Epilepsies as dynamical diseases of brain systems: basic models of the transition
      between normal and epileptic activity.
AB  - PURPOSE: The occurrence of abnormal dynamics in a physiological system can become
      manifest as a sudden qualitative change in the behavior of characteristic
      physiologic variables. We assume that this is what happens in the brain with
      regard to epilepsy. We consider that neuronal networks involved in epilepsy
      possess multistable dynamics (i.e., they may display several dynamic states). To
      illustrate this concept, we may assume, for simplicity, that at least two states
      are possible: an interictal one characterized by a normal, apparently random,
      steady-state of ongoing activity, and another one that is characterized by the
      paroxysmal occurrence of a synchronous oscillations (seizure). METHODS: By using
      the terminology of the mathematics of nonlinear systems, we can say that such a
      bistable system has two attractors, to which the trajectories describing the
      system's output converge, depending on initial conditions and on the system's
      parameters. In phase-space, the basins of attraction corresponding to the two
      states are separated by what is called a "separatrix." We propose, schematically,
      that the transition between the normal ongoing and the seizure activity can take
      place according to three basic models: Model I: In certain epileptic brains
      (e.g., in absence seizures of idiopathic primary generalized epilepsies), the
      distance between "normal steady-state" and "paroxysmal" attractors is very small
      in contrast to that of a normal brain (possibly due to genetic and/or
      developmental factors). In the former, discrete random fluctuations of some
      variables can be sufficient for the occurrence of a transition to the paroxysmal
      state. In this case, such seizures are not predictable. Model II and model III:
      In other kinds of epileptic brains (e.g., limbic cortex epilepsies), the distance
      between "normal steady-state" and "paroxysmal" attractors is, in general, rather
      large, such that random fluctuations, of themselves, are commonly not capable of
      triggering a seizure. However, in these brains, neuronal networks have abnormal
      features characterized by unstable parameters that are very vulnerable to the
      influence of endogenous (model II) and/or exogenous (model III) factors. In these
      cases, these critical parameters may gradually change with time, in such a way
      that the attractor can deform either gradually or suddenly, with the consequence
      that the distance between the basin of attraction of the normal state and the
      separatrix tends to zero. This can lead, eventually, to a transition to a
      seizure. RESULTS: The changes of the system's dynamics preceding a seizure in
      these models either may be detectable in the EEG and thus the route to the
      seizure may be predictable, or may be unobservable by using only measurements of
      the dynamical state. It is thinkable, however, that in some cases, changes in the
      excitability state of the underlying networks may be uncovered by using
      appropriate stimuli configurations before changes in the dynamics of the ongoing
      EEG activity are evident. A typical example of model III that we discuss here is
      photosensitive epilepsy. CONCLUSIONS: We present an overview of these basic
      models, based on neurophysiologic recordings combined with signal analysis and on
      simulations performed by using computational models of neuronal networks. We pay
      especial attention to recent model studies and to novel experimental results
      obtained while analyzing EEG features preceding limbic seizures and during
      intermittent photic stimulation that precedes the transition to paroxysmal
      epileptic activity.

PMID- 14641565
TI  - Classification of the myoclonic epilepsies.
AB  - The myoclonic epilepsies are a collection of syndromes in which myoclonic
      seizures are a prominent feature. Proper classification of a patient's syndrome
      is critical for appropriate treatment and prognosis. However, classification of
      such syndromes is often difficult because the terminology used to describe
      seizures can be confusing and inconsistent. Myoclonic epilepsy syndromes can be
      epileptic or nonepileptic and can also be divided into inherited and acquired
      forms. Progressive myoclonic epilepsy (PME) syndromes are the most severe of the
      myoclonic epilepsies. Diagnosis of PME syndromes on clinical grounds can be
      difficult, but advances in genetic testing have made diagnoses more accurate.
      Some other benign myoclonic epilepsy syndromes also have identified gene markers,
      which can aid in diagnosis. To accurately classify a patient's epilepsy syndrome,
      clinicians should use all available clinical laboratory tools appropriately.
      Improved accuracy of diagnosis for patients with myoclonic epilepsies should lead
      to more dependable prognoses and more effective treatment.

PMID- 14641566
TI  - Clinical presentations and phenomenology of myoclonus.
AB  - The term "myoclonus" has been used to describe heterogeneous phenomena involving
      sudden movements, but there is no generally accepted, precise definition of
      myoclonus. Myoclonus can often be classified based on electroencephalographic
      (EEG) and/or electromyographic (EMG) data. Some myoclonic epilepsy syndromes,
      including juvenile myoclonic epilepsy, may frequently be misdiagnosed because of
      failure to obtain a complete patient history and/or failure to appreciate
      characteristic EEG changes. A good understanding of the features associated with
      myoclonic disorders (particularly the myoclonic epilepsies) and of features
      associated with other neurologic disorders that are often confused with myoclonic
      disorders is an invaluable aid in obtaining an accurate diagnosis and will
      ultimately help in determining the best course of treatment for patients.

PMID- 14641567
TI  - Recent developments in the quest for myoclonic epilepsy genes.
AB  - Understanding the latest advances in the molecular genetics of the epilepsies is
      important, as it provides a basis for comprehending the new practice of
      epileptology. Epilepsies have traditionally been classified and subtyped on the
      basis of clinical and neurophysiologic concepts. However, the complexity and
      variability of phenotypes and overlapping clinical features limit the resolution
      of phenotype-based classification and confound epilepsy nosology. Identification
      of tightly linked epilepsy DNA markers and discovery of epilepsy-causing
      mutations provide a basis for refining the classification of epilepsies. Recent
      discoveries regarding the genetics surrounding certain epilepsy types (including
      Lafora's progressive myoclonic epilepsy, the severe myoclonic epilepsy of infancy
      of Dravet, and idiopathic generalized epilepsies) may be the beginning of a
      better understanding of how rare Mendelian epilepsy genes and their genetic
      architecture can explain some complexities of the common epilepsies.

PMID- 14641568
TI  - Treatment strategies for myoclonic seizures and epilepsy syndromes with myoclonic
      seizures.
AB  - Despite the availability of numerous treatment options, the diagnosis and
      treatment of myoclonic seizures continue to be challenging. Based on clinical
      experience, valproate and benzodiazepines have historically been used to treat
      myoclonic seizures. However, many more treatment options exist today, and the
      clinician must match the appropriate treatment with the patient's epilepsy
      syndrome and its underlying etiology. Comorbidities and other medications must
      also be considered when making decisions regarding treatment. Rarely, some
      antiepileptic drugs may exacerbate myoclonic seizures. Most epileptic myoclonus
      can be treated pharmacologically, but some cases respond better to surgery, the
      ketogenic diet, or vagus nerve stimulation. Because myoclonic seizures can be
      difficult to treat, clinicians should be flexible in their approach and tailor
      therapy to each patient.

PMID- 14641569
TI  - The future of microbial genomics.

PMID- 14641570
TI  - Integrated regulation in response to aromatic compounds: from signal sensing to
      attractive behaviour.
AB  - Deciphering the complex interconnecting bacterial responses to the presence of
      aromatic compounds is required to gain an integrated understanding of how
      aromatic catabolic processes function in relation to their genome and
      environmental context. In addition to the properties of the catabolic enzymes
      themselves, regulatory responses on at least three different levels are
      important. At a primary level, aromatic compounds control the activity of
      specific members of many families of transcriptional regulators to direct the
      expression of the specialized enzymes for their own catabolism. At a second
      level, dominant global regulation in response to environmental and physiological
      cues is incorporated to subvert and couple transcription levels to the energy
      status of the bacteria. Mediators of these global regulatory responses include
      the alarmone (p)ppGpp, the DNA-bending protein IHF and less well-defined systems
      that probably sense the energy status through the activity of the electron
      transport chain. At a third level, aromatic compounds can also impact on
      catabolic performance by provoking behavioural responses that allow the bacteria
      to seek out aromatic growth substrates in their environment.

PMID- 14641571
TI  - Heavy metal tolerance and metal homeostasis in Pseudomonas putida as revealed by
      complete genome analysis.
AB  - The genome of Pseudomonas putida KT2440 encodes an unexpected capacity to
      tolerate heavy metals and metalloids. The availability of the complete
      chromosomal sequence allowed the categorization of 61 open reading frames likely
      to be involved in metal tolerance or homeostasis, plus seven more possibly
      involved in metal resistance mechanisms. Some systems appeared to be duplicated.
      These might perform redundant functions or be involved in tolerance to different
      metals. In total, P. putida was found to bear two systems for arsenic (arsRBCH),
      one for chromate (chrA), four to six systems for divalent cations (two cadA and
      two to four czc chemiosmotic antiporters), two systems for monovalent cations:
      pacS, cusCBA (plus one cryptic silP gene containing a frameshift mutation), two
      operons for Cu chelation (copAB), one metallothionein for metal(loid) binding,
      one system for Te/Se methylation (tpmT) and four ABC transporters for the uptake
      of essential Zn, Mn, Mo and Ni (one nikABCDE, two znuACB and one mobABC). Some of
      the metal-related clusters are located in gene islands with atypical genome
      signatures. The predicted capacity of P. putida to endure exposure to heavy
      metals is discussed from an evolutionary perspective.

PMID- 14641572
TI  - Proteome reference map of Pseudomonas putida strain KT2440 for genome expression
      profiling: distinct responses of KT2440 and Pseudomonas aeruginosa strain PAO1 to
      iron deprivation and a new form of superoxide dismutase.
AB  - The genome sequence of Pseudomonas putida strain KT2440, a nutritionally
      versatile, saprophytic and plant root-colonizing Gram-negative soil bacterium,
      was recently determined by K. E. Nelson et al. (2002, Environ Microbiol 4: 799
      808). Here, we present a two-dimensional gel protein reference map of KT2440
      cells grown in mineral salts medium with glucose as carbon source. Proteins were
      identified by matrix-assisted laser desorption ionization time-of-flight (MALDI
      TOF) analysis, in conjunction with an in-house database developed from the genome
      sequence of KT2440, and approximately 200 two-dimensional gel spots were
      assigned. The map was used to assess the genomic response of KT2440 to iron
      limitation stress and to compare this response with that of the closely related
      facultative human pathogen Pseudomonas aeruginosa strain PAO1. The synthesis of
      about 25 proteins was affected in both strains, including four prominent
      upregulated ferric uptake regulator (Fur) protein-dependent proteins, but there
      were also striking differences in their proteome responses, for example in the
      expression of superoxide dismutases (Sod), which may indicate important roles of
      iron-responsive functions in the adaptation of these two bacteria to different
      lifestyles. The Sod enzyme of KT2440 was shown to be a novel heterodimer of the
      SodA and SodB polypeptides.

PMID- 14641573
TI  - Chaotropic solutes cause water stress in Pseudomonas putida.
AB  - Low water availability is the most ubiquitous cause of stress for terrestrial
      plants, animals and microorganisms, and has a major impact on ecosystem function
      and agricultural productivity. Studies of water stress have largely focused on
      conditions that affect cell turgor, i.e. induce osmotic stress. We show that
      chaotropic solutes that do not affect turgor reduce water activity, perturb
      macromolecule-water interactions and thereby destabilize cellular macromolecules,
      inhibit growth, and are powerful mediators of water stress in a typical soil
      bacterium, Pseudomonas putida. Chaotropic solute-induced water stress resulted
      mostly in the upregulation of proteins involved in stabilization of biological
      macromolecules and membrane structure. Many environmental pollutants and
      agricultural products are chaotropic chemicals and thus constitute a previously
      unrecognised but common form of biological stress in water bodies and soils.

PMID- 14641574
TI  - The sigma54 regulon (sigmulon) of Pseudomonas putida.
AB  - sigma54 is unique among the bacterial sigma factors. Besides not being related in
      sequence with the rest of such factors, its mechanism of transcription initiation
      is completely different and requires the participation of a transcription
      activator. In addition, whereas the rest of the alternative sigma factors use to
      be involved in transcription of somehow related biological functions, this is not
      the case for sigma54 and many different and unrelated genes have been shown to be
      transcribed from sigma54-dependent promoters, ranging from flagellation, to
      utilization of several different carbon and nitrogen sources, or alginate
      biosynthesis. These genes have been characterized in many different bacterial
      species and, only until recently with the arrival of complete genome sequences,
      we have been able to look at the sigma54 functional role from a genomic
      perspective. Aided by computational methods, the sigma54 regulon has been studied
      both in Escherichia coli, Salmonella typhimurium and several species of the
      Rhizobiaceae. Here we present the analysis of the sigma54 regulon (sigmulon) in
      the complete genome of Pseudomonas putida KT2440. We have developed an improved
      method for the prediction of sigma54-dependent promoters which combines the
      scores of sigma54-RNAP target sequences and those of activator binding sites. In
      combination with other evidence obtained from the chromosomal context and the
      similarity with closely related bacteria, we have been able to predict more than
      80% of the sigma54-dependent promoters of P. putida with high confidence. Our
      analysis has revealed new functions for sigma54 and, by means of comparative
      analysis with the previous studies, we have drawn a potential mechanism for the
      evolution of this regulatory system.

PMID- 14641575
TI  - In vivo functional genomics of Pseudomonas aeruginosa for high-throughput
      screening of new virulence factors and antibacterial targets.
AB  - Pseudomonas aeruginosa is a model for studying opportunistic pathogens that are
      highly resistant to most classes of antibiotics and cause chronic pulmonary
      infections. We have developed and adapted a multiplex polymerase chain reaction
      based signature-tagged mutagenesis (STM) for high-throughput screening of a
      collection of 7968 P. aeruginosa mutants in a rat model of chronic respiratory
      infection. After three rounds of screening, a total of 214 mutants, representing
      transposition events into 148 open reading frames, were shown to be attenuated in
      lung infection and were retained for further analysis. As proof of concept
      supporting this technology, we identified 11 insertions in typical virulence
      genes such as those coding for pili implicated in motility, attachment and
      swarming, alginate synthesis and its expression, a mucus transcription regulator,
      extracellular enzymes such as alkaline protease, esterase and amino peptidase, a
      rhamnosyl surfactant transferase and a lipopolysaccharide glycosyl transferase.
      Detailed analysis of the 148 STM mutants, including seven auxotrophs, revealed
      insertions in 21 of the 26 known gene classes used to characterize sequenced
      bacterial genomes. We noted that at least 46% of STM mutants identified had
      insertions in hypothetical proteins or proteins of unknown function and that
      approximately 40% of all STM mutants had insertions in surface proteins including
      the outer membrane, the periplasm and the inner membrane. Interestingly, 11 STM
      mutants attenuated for lung infection were also identified in microarray and
      transcriptome for quorum sensing and mucoidy production. The remaining 130
      mutants were systematically analysed for their capability to express fully known
      virulence factors. In addition, testing the ability of these mutants to infect
      alternative model host Drosophila melanogaster revealed 36 STM mutants defective
      in protease, twitching motility, swimming and swarming. Finally, we identified
      many genes, the activity of which in respiratory infection was not fully
      appreciated.

PMID- 14641576
TI  - Characterization of a new solvent-responsive gene locus in Pseudomonas putida F1
      and its functionalization as a versatile biosensor.
AB  - A new gene cluster, designated sepABC and a divergently transcribed sepR, was
      found downstream of the two-component todST phosphorelay system that regulates
      toluene degradation (the tod pathway) in Pseudomonas putida F1 (PpF1). The
      deduced amino acid sequences encoded by sepABC show a high homology to bacterial
      proteins known to be involved in solvent efflux or multidrug pumps. SepA, SepB
      and SepC are referred to be periplasmic, inner membrane and outer membrane efflux
      proteins respectively. Effects on growth of various PpF1 mutants compared to that
      of the wild type in the presence of toluene indicated a possible protective role
      of the solvent efflux system in a solvent-stressed environment. Growth tests with
      the complemented mutants confirmed the involvement of the Sep proteins in
      conferring solvent tolerance. The sepR gene encodes a 260-residue polypeptide
      that is a member of the E. coli IclR repressor protein family. The repressor role
      of SepR was established by conducting tests with a sep-lacZ transcriptional
      fusion in Escherichia coli and PpF1, expression of SepR as a maltose-binding
      fusion protein in a DNA binding assay, and mRNA analysis. Southern hybridization
      experiments and analysis of the P. putida KT2440 genome sequence indicated that
      sepR is a relatively rare commodity compared to homologues of the sepABC genes.
      We developed a whole-cell bioluminescent biosensor, PpF1G4, which contains a
      chromosomally based sep-lux transcriptional fusion. The biosensor showed
      significant induction of the sepABC genes by a wide variety of aromatic
      molecules, including benzene, toluene, ethylbenzene, and all three isomers of
      xylene (BTEX), naphthalene, and complex mixtures of aliphatic and aromatic
      hydrocarbons. PpF1G4 represents a second-generation biosensor that is not based
      on a catabolic promoter but is nonetheless inducible by aromatic pollutants and
      moreover functional under nutrient-rich conditions.

PMID- 14641577
TI  - Conservation of the response regulator gene gacA in Pseudomonas species.
AB  - The response regulator gene gacA influences the production of several secondary
      metabolites in both pathogenic and beneficial Pseudomonas spp. In this study, we
      developed primers and a probe for the gacA gene of Pseudomonas species and
      sequenced a 425 bp fragment of gacA from ten Pseudomonas strains isolated from
      different plant-associated environments. Polymerase chain reaction analysis and
      Southern hybridization showed that gacA is highly conserved within the genus
      Pseudomonas: multiple strains of different Pseudomonas species all responded
      positively to the probe, whereas no response was obtained from 18 other strains
      representing 14 species that belong to eight different genera of Gram-negative
      bacteria other than Pseudomonas. Furthermore, from a total of approximately 550
      indigenous bacterial isolates obtained from the rhizosphere of wheat, all
      isolates that hybridized with the gacA probe were classified as Pseudomonas spp.
      by group-specific primers. Isolates that did not respond with the gacA probe and
      primers were identified as bacterial genera other than Pseudomonas, including
      Stenotrophomonas, Cryseomonas and Comamonas spp. These results indicate that gacA
      can be used as a complementary genetic marker for detection of Pseudomonas spp.
      in environmental samples. Phylogenetic relationships inferred from the newly
      sequenced gacA fragments and the sequences of gacA homologues present in the
      databases, showed six distinct clusters that correspond to the following
      bacterial families: Pseudomonaceae, Enterobacteriaceae, Alteromonadaceae,
      Vibrionaceae, Burkholderia and Xanthomonas. Within the Pseudomonadaceae and
      Enterobacteriaceae, polymorphisms within gacA and its homologues allowed
      identification of six and five subclusters respectively. Comparison of the gacA
      gene and GacA protein-based trees with the tree inferred from 16S rDNA sequences
      yielded a similar overall clustering. These results suggest that gacA and its
      homologues may provide complementary markers for phylogenetic studies of
      Pseudomonas spp. and Gram-negative bacteria other than Pseudomonas.

PMID- 14641578
TI  - Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates
      from the airways of young children with cystic fibrosis.
AB  - Pseudomonas aeruginosa strains from the chronic lung infections of cystic
      fibrosis (CF) patients are phenotypically and genotypically diverse. Using strain
      PAO1 whole genome DNA microarrays, we assessed the genomic variation in P.
      aeruginosa strains isolated from young children with CF (6 months to 8 years of
      age) as well as from the environment. Eighty-nine to 97% of the PAO1 open reading
      frames were detected in 20 strains by microarray analysis, while subsets of 38
      gene islands were absent or divergent. No specific pattern of genome mosaicism
      defined strains associated with CF. Many mosaic regions were distinguished by
      their low G + C content; their inclusion of phage related or pyocin genes; or by
      their linkage to a vgr gene or a tRNA gene. Microarray and phenotypic analysis of
      sequential isolates from individual patients revealed two deletions of greater
      than 100 kbp formed during evolution in the lung. The gene loss in these
      sequential isolates raises the possibility that acquisition of pyomelanin
      production and loss of pyoverdin uptake each may be of adaptive significance.
      Further characterization of P. aeruginosa diversity within the airways of
      individual CF patients may reveal common adaptations, perhaps mediated by gene
      loss, that suggest new opportunities for therapy.

PMID- 14641579
TI  - Identification of quorum-sensing regulated proteins in the opportunistic pathogen
      Pseudomonas aeruginosa by proteomics.
AB  - The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic human
      pathogen which is responsible for severe nosocomial infections in
      immunocompromised patients and is the major pathogen in cystic fibrosis. The
      bacterium utilizes two interrelated quorum-sensing (QS) systems, which rely on N
      acyl-homoserine lactone (AHL) signal molecules, to control the expression of
      virulence factors and biofilm development. In this study, we compared the protein
      patterns of the intracellular, extracellular and surface protein fractions of the
      PAO1 parent strain with those of an isogenic lasI rhlI double mutant by means of
      two-dimensional gel electrophoresis (2-DE). This analysis showed that the
      intensities of 23.7% of all detected protein spots differed more than 2.5-fold
      between the two strains. We only considered those protein spots truly QS
      regulated that were changed in the mutant in the absence of signal molecules but
      were rescued to the wild-type situation when the medium was supplemented with
      AHLs. These protein spots were characterized by MALDI-TOF peptide mapping. Twenty
      seven proteins were identified that were previously reported to be AHL
      controlled, among them several well-characterized virulence factors. For one of
      the identified proteins, the serine protease PrpL, a biochemical assay was
      established to verify that expression of this factor is indeed QS regulated.
      Furthermore, it is shown that the quorum-sensing blocker C-30 specifically
      interferes with the expression of 67% of the AHL-controlled protein spots of the
      surface fraction, confirming the high specificity of the compound. Importantly,
      20 novel QS-regulated proteins were identified, many of which are involved in
      iron utilization, suggesting a link between quorum sensing and the iron
      regulatory system. Two of these proteins, PhuR and HasAp, are components of the
      two distinct haem-uptake systems present in P. aeruginosa. In agreement with the
      finding that both proteins are positively regulated by the QS cascade, we show
      that the lasI rhlI double mutant grows poorly with haemoglobin as the only iron
      source when compared with the wild type. These results add haemoglobin
      utilization to the list of phenotypes controlled through QS in P. aeruginosa. The
      surprisingly high number of AHL-regulated proteins relative to the number of
      regulated genes suggests that quorum-sensing control also operates via post
      transcriptional mechanisms. To strengthen this hypothesis we investigated the
      role of quorum sensing in the post-translational modification of HasAp, an
      extracellular protein required for the uptake of free and haemoglobin-bound haem.

PMID- 14641582
TI  - Scaling up: the next challenge in environmental microbiology.
AB  - Great strides have recently been made in identifying and characterizing the
      staggering diversity of microorganisms conducting primary and secondary
      production, nutrient transformation and mineralization processes that underlie
      ecosystem and regional biogeochemical, trophodynamic and ecological change. We
      are now faced with the challenge of assigning and coupling function to structure
      in highly complex and interactive microbial communities mediating such change.
      Previous and ongoing ecophysiological work has shown that microbial processes
      controlled by environmental variables and limiting resources are highly specific
      in terms of what, when, where and why they are active, not to mention how they
      impact ecosystem dynamics. As such, it is imperative that we assess the
      activities and roles of key microbial 'players' along the appropriate
      environmental scales and gradients catalysing ecological change. Here, we discuss
      conceptual and technical challenges for some key microbially mediated
      environmental processes, problems and extremes that require synthesizing our
      growing knowledge of microbial community structure with emerging knowledge of
      function in aquatic ecosystems. We emphasize the importance of assessing
      ecological change over a range of relevant time scales that vary from minutes to
      millennia and spatial scales that range from microscale aggregates to ocean
      basins.

PMID- 14641583
TI  - Diversity of bacteriorhodopsins in different hypersaline waters from a single
      Spanish saltern.
AB  - Haloarchaeal rhodopsins are a diverse group of transmembrane proteins that use
      light energy to drive several different cellular processes. Two rhodopsins,
      bacteriorhodopsin and halorhodopsins, are H+ and Cl- ion pumps, respectively, and
      two rhodopsins, sensory rhodopsin I and II, regulate phototaxis.
      Bacteriorhodopsin is of special interest as it is a non-chlorophyll-based type of
      phototrophy (i.e. generation of chemical energy from light energy). However, very
      little is known about the diversity and distribution of rhodopsin genes in
      hypersaline environments. Here, we have used environmental PCR and cloning
      techniques to directly retrieve rhodopsin genes from three different salinity
      ponds located in a sea salt manufacturing facility near Alicante, Spain. Our
      survey resulted in the discovery of previously concealed variation including what
      is hypothesized to be bacteriorhodopsin genes from the uncultivated square
      morphotype that dominates these environments. In some instances, identical genes
      were discovered in seemingly different habitats suggesting that some haloarchaea
      are present over widely varying concentrations of salt.

PMID- 14641584
TI  - Multiple species of the dinophagous dinoflagellate genus Amoebophrya infect the
      same host species.
AB  - Populations of the dinoflagellate Dinophysis norvegica in the Baltic Sea and in
      the adjacent North Sea are infected by the endoparasite Amoebophrya sp. The high
      diversity recently unveiled within the genus Amoebophrya brings uncertainty about
      their identities. We applied molecular biology techniques--18S rDNA sequencing
      and fluorescent in situ hybridization (FISH)--to compare this host-parasite
      system from both environments. The North Sea Amoebophrya sp. 18S rDNA sequence
      was 89% identical to the previously described Baltic Sea Amoebophrya sp.
      sequence, suggesting they are different species. In spite of that, a
      phylogenetical analysis placed the North Sea parasite sequence in a well
      supported cluster with other Amoebophrya sp. sequences. The D. norvegica 18S rDNA
      sequences from both environments were 100% identical, indicating that the hosts
      have not evolved independently. A DNA probe designed for the Baltic Sea
      Amoebophrya sp. 18S rRNA was used in FISH assays on infected D. norvegica
      populations from both environments. The probe stained all infected cells from the
      Baltic sample, whereas none from the North Sea were stained. The results indicate
      that D. norvegica is released from one parasite when entering the Baltic Sea, and
      become less infected by an alternative parasite species.

PMID- 14641585
TI  - The significance of organic carbon compounds for in situ metabolism and
      chemotaxis of phototrophic consortia.
AB  - The significance of organic carbon substrates for the chemotaxis and physiology
      of phototrophic consortia was investigated in a dense chemocline community of
      Pelochromatium roseum. For the first time, the monopolar monotrichous
      flagellation of the central bacterium could be visualized. In situ, intact motile
      P. roseum consortia were strongly attracted by sulphide and 2-oxoglutarate, which
      indicated a potential role of these compounds in the metabolism of P. roseum. In
      chemocline water samples, 2-[14C(U)]-oxoglutarate was utilized at nanomolar
      concentrations (half saturation constant of uptake Kt < or = 10-40 nM), and at a
      maximum uptake rate of Vmax approximately 6 nM h-1. The calculated turnover of 2
      oxoglutarate at in situ concentrations was approximately 6 h.
      Microautoradiography of chemocline water samples revealed that 87.5% of the P.
      roseum consortia incorporated 2-oxoglutarate when both light and sulphide were
      present, whereas uptake was detected in less than 1.4% of the consortia if either
      light or sulphide were absent. Because the green sulphur bacterial epibionts in
      P. roseum have been shown to grow autotrophically, 2-oxoglutarate most likely is
      taken up and utilized by the central bacterium. Thus, our results indicate that
      incorporation of 2-oxoglutarate by the central bacterium is regulated by the
      metabolic state of the green sulphur bacterial epibionts.

PMID- 14641586
TI  - Effect of growth temperature on cellular fatty acids in sulphate-reducing
      bacteria.
AB  - The effect of growth temperature on the cellular fatty acid composition of
      sulphate-reducing bacteria (SRB) was studied in 12 species belonging to eight
      genera including psychrophiles and mesophiles. Most of these species were of
      marine origin. The investigated SRB with the exception of four Desulfobacter
      species exhibited only a minor increase in the proportion of cis-unsaturated
      fatty acids (by < or = 5% per 10 degrees C) when the growth temperature was
      decreased; psychrophiles maintained their typically high content of cis
      unsaturated fatty acids (around 75% of total fatty acids) nearly constant. The
      four Desulfobacter species, however, increased the proportion of cis-unsaturated
      among total fatty acids significantly (by > or =14% per 10 degrees C; measured in
      late growth phase) with decreasing growth temperature. The ratio between
      unsaturated and saturated fatty acids in Desulfobacter species changed not only
      with the growth temperature, but also with the growth state in batch cultures at
      constant temperature. Changes of cellular fatty acids were studied in detail with
      D. hydrogenophilus, the most psychrotolerant (growth range 0-35 degrees C) among
      the mesophilic SRB examined. Desulfobacter hydrogenophilus also formed cis-9,10
      methylenehexadecanoic acid (a cyclopropane fatty acid) and 10-methylhexadecanoic
      acid. At low growth temperature (12 degrees C), the relative amount of these
      fatty acids was at least threefold lower; this questions the usefulness of 10
      methylhexadecanoic acid as a reliable biomarker of Desulfobacter in cold
      sediments.

PMID- 14641587
TI  - Diverse microbial communities inhabiting ferromanganese deposits in Lechuguilla
      and Spider Caves.
AB  - Lechuguilla Cave is an ancient, deep, oligotrophic subterranean environment that
      contains an abundance of low-density ferromanganese deposits, the origin of which
      is uncertain. To assess the possibility that biotic factors may be involved in
      the production of these deposits and to investigate the nature of the microbial
      community in these materials, we carried out culture-independent, small subunit
      ribosomal RNA (SSU rRNA) sequence-based studies from two sites and from manganese
      and iron enrichment cultures inoculated with ferromanganese deposits from
      Lechuguilla and Spider Caves. Sequence analysis showed the presence of some
      organisms whose closest relatives are known iron- and manganese
      oxidizing/reducing bacteria, including Hyphomicrobium, Pedomicrobium,
      Leptospirillum, Stenotrophomonas and Pantoea. The dominant clone types in one
      site grouped with mesophilic Archaea in both the Crenarchaeota and Euryarchaeota.
      The second site was dominated almost entirely by lactobacilli. Other clone
      sequences were most closely related to those of nitrite-oxidizing bacteria,
      nitrogen-fixing bacteria, actinomycetes and beta- and gamma-Proteobacteria.
      Geochemical analyses showed a fourfold enrichment of oxidized iron and manganese
      from bedrock to darkest ferromanganese deposits. These data support our
      hypothesis that microorganisms may contribute to the formation of manganese and
      iron oxide-rich deposits and a diverse microbial community is present in these
      unusual secondary mineral formations.

PMID- 14641588
TI  - Arsenate transport and reduction in the hyper-tolerant fungus Aspergillus sp.
      P37.
AB  - Aspergillus sp. P37 is able to grow at arsenate concentrations of 0.2 M--more
      than 20-fold higher than that withstood by reference microorganisms such
      Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. This paper
      examines the transport of arsenate and phosphate and the reduction of arsenate in
      Aspergillus sp. P37. These properties were compared with the corresponding
      properties of the archetype strain Aspergillus nidulans TS1. Both uptake and
      efflux of arsenate were inhibited by carbonyl cyanide-p
      trifluoromethoxyphenylhydrazone, suggesting that the transport system(s) is(are)
      membrane-potential dependent. As uptake of arsenate and phosphate are higher in
      Aspergillus sp. P37 than in A. nidulans, the increase in arsenate resistance
      cannot be accounted for by a change in uptake. Cells of both strains loaded with
      arsenic slowly released the oxyanion. Speciation of the arsenic in the medium
      showed an enhanced level of arsenate reduction in Aspergillus sp. P37. These data
      suggest that increased arsenate reduction is at least in part responsible for the
      hyper-tolerant phenotype of this fungus.

PMID- 14641589
TI  - Isolation of Halobacterium salinarum retrieved directly from halite brine
      inclusions.
AB  - Halite crystals were selected from a 186 m subsurface core taken from the
      Badwater salt pan, Death Valley, California to ascertain if halophilic Archaea
      and their associated 16S rDNA can survive over several tens of thousands of
      years. Using a combined microscope microdrill/micropipette system, fluids from
      brine inclusions were aseptically extracted from primary, hopper texture, halite
      crystals from 8 and 85 metres below the surface (mbls). U-Th disequilibrium
      dating indicates that these halite layers were deposited at 9,600 and 97,000
      years before present (ybp) respectively. Extracted inclusions were used for
      polymerase chain reaction (PCR) analysis with haloarchaea-specific 16S rDNA
      primers or placed into haloarchaea culture medium. Enrichment cultures were
      obtained from 97 kyr halite crystal inclusion fluid and haloarchaea-containing
      prepared crystals (positive controls), whereas inclusions from crystals of 9.6
      kyr halite and the haloarchaea-free halite crystals (negative controls) resulted
      in no growth. Phylogenetic analysis (16S rDNA) of the 97 kyr isolate, designated
      BBH 001, revealed a homology of 100% with Halobacterium salinarum. DNA-DNA
      hybridization experiments confirmed that BBH 001 was closely related to H.
      salinarum (81-75% hybridization) and its ascription to this haloarchaea species.
      The described method of retrieving particle-containing brine from fluid
      inclusions offers a robust approach for assessing the antiquity of microorganisms
      associated with evaporites.

PMID- 14641590
TI  - Distribution of chloropigments in suspended particulate matter and benthic
      microbial mat of a meromictic lake, Lake Kaiike, Japan.
AB  - We investigated the distribution of chloropigments in a small meromictic lake,
      Lake Kaiike, south-west Japan. In the water-column, concentrations of Chl a
      related to cyanobacteria, BChl a related to purple sulphur bacteria, and three
      types of BChl e homologues (BChls e1, e2 and e3) related to brown-coloured green
      sulphur bacteria, were maximal at the redox boundary. Below the redox boundary,
      absolute concentrations of Chl a and BChl a gradually decreased with depth,
      whereas BChls e remained rather constant. Suspended particulate matter (SPM) at
      the deeper region of the anoxic water-column was enriched in highly alkylated
      BChl e homologues compared with SPM at the redox boundary. The shift in the
      relative content of highly alkylated BChl e homologues beneath the boundary was
      associated with community related adaptation of brown-coloured green sulphur
      bacteria to changes in light quality/quantity, resulting from the optical
      absorption and reflectance of SPMs in the overlying water-column. Benthic
      microbial mats were characterized by high abundances of BChls e, in which highly
      alkylated homologues were substantially abundant. This suggests that the BChls e
      in the microbial mat may be derived from the low-light adapted brown-coloured
      green sulphur bacteria forming the bacterial mat.

PMID- 14641592
TI  - Diversity of fungi in organic soils under a moorland--Scots pine (Pinus
      sylvestris L.) gradient.
AB  - The conservation and regeneration of native Scots pine (Pinus sylvestris L.)
      woodlands is being actively encouraged by conservation agencies in the UK because
      of their high biodiversity value. In the present study, the consequences of
      regeneration on terrestrial fungal communities was determined in three parallel
      transects running from open moorland, through an intermediate zone showing
      seedling colonization, into a mature Scots pine forest at Abernethy Forest,
      Cairngorm, Scotland. Soil cores were taken at 18 m intervals along each 180 m
      transect, and the diversity of the soil fungal community was investigated by DGGE
      and sequence analysis of ITS fragments PCR-amplified from DNA extracted from
      soil. Analysis of DGGE profiles generated for two of the three transects
      indicates a clear shift in the community from the moorland region of the
      transects to the forest region. Whereas a few bands were present at all sampling
      points across the transects, the majority of bands were unique to either the
      moorland or forest samples. FASTA database searches of ITS sequence data
      generated from excised DGGE bands revealed the closest species match for each
      band. In some cases, the similarity of ITS sequences to database sequences was
      poor, but the remaining sequences were most closely related to ITS sequences of
      both mycorrhizal and non-mycorrhizal fungi. The data are discussed in relation to
      the effect of native pine woodland expansion on the soil fungal community.

PMID- 14641591
TI  - Sampling strategy in molecular microbial ecology: influence of soil sample size
      on DNA fingerprinting analysis of fungal and bacterial communities.
AB  - Assessing soil microbial community structure by the use of molecular techniques
      requires a satisfactory sampling strategy that takes into account the high
      microbial diversity and the heterogeneous distribution of microorganisms in the
      soil matrix. The influence of the sample size of three different soil types
      (sand, silt and clay soils) on the DNA yield and analysis of bacterial and fungal
      community structure were investigated. Six sample sizes from 0.125 g to 4 g were
      evaluated. The genetic community structure was assessed by automated ribosomal
      intergenic spacer analysis (A-RISA fingerprint). Variations between bacterial (B
      ARISA) and fungal (F-ARISA) community structure were quantified by using
      principal component analysis (PCA). DNA yields were positively correlated with
      the sample size for the sandy and silty soils, suggesting an influence of the
      sample size on DNA recovery, whereas no correlation was observed in the clay
      soil. B-ARISA was shown to be consistent between the different sample sizes for
      each soil type indicating that the sampling procedure has no influence on the
      assessment of bacterial community structure. On the contrary for F-ARISA
      profiles, strong variations were observed between replicates of the smaller
      samples (<1 g). Principal component analysis analysis revealed that sampling
      aliquots of soil > or =1 g are required to obtain robust and reproducible
      fingerprinting analysis of the genetic structure of fungal communities. However,
      the smallest samples could be adequate for the detection of minor populations
      masked by dominant ones in larger samples. The sampling strategy should therefore
      be different according to the objectives: rather large soil samples (> or =1 g)
      for a global description of the genetic community structure, or a large number of
      small soil samples for a more complete inventory of microbial diversity.

PMID- 14641593
TI  - Microsite-dependent changes in methanogenic populations in a boreal oligotrophic
      fen.
AB  - Wetlands, including peatlands, are the main source of natural methane emission.
      Well-defined fen microsites have different methane emissions rates, but it is not
      known whether the methane-producing Archaea communities vary at these sites.
      Possible horizontal variations of communities, in a natural oligotrophic fen,
      were analysed by characterizing the methanogens from two well-defined microsites:
      Eriophorum lawn and Hummock. Community structures were studied at two different
      layers of the fen, showing, respectively, high and low methane production. The
      structure of methanogen populations was determined using molecular techniques
      targeting the 16SrRNA gene and combined denaturing gradient gel electrophoresis
      (DGGE) and restriction fragment length polymorphism (RFLP) analysis. Results
      subjected to non-metric multidimensional scaling (MDS), diversity indices
      calculation and phylogenetic analysis revealed that upper layer communities
      changed with site while deeper layer communities remained the same. Phylogenetic
      analyses revealed six different clusters of sequences grouping with only two
      known orders of methanogens. Upper layers of Hummock were dominated by sequences
      clustering with members of Methanomicrobiales and sequences dominating the upper
      part of the Eriophorum lawn were related to members of the order
      Methanosarcinales. Novel methanogenic sequences were found at both sites at both
      depths. Vegetation characterizing the microsites probably influences the
      microbial communities in the layers of the fen where methane is produced.

PMID- 14641594
TI  - Targeting clusters of transferred genes in Thermotoga maritima.
AB  - We screened a Thermotoga sp. strain RQ2 lambda library for genes present in that
      strain but absent from the closely related completely sequenced relative
      Thermotoga maritima strain MSB8, by using probes generated in an earlier genomic
      subtraction study. Five lambda insert fragments were sequenced, containing,
      respectively, an archaeal type ATPase operon, rhamnose biosynthetic genes, ORFs
      with similarity to an arabinosidase, a Thermotoga sp. strain RQ2-specific alcohol
      dehydrogenase and a novel archaeal Mut-S homologue. All but one of these
      fragments contained additional Thermotoga sp. strain RQ2-specific sequences not
      screened for, suggesting that many such strain-specific genes will be found
      clustered in the genome. Moreover, phylogenetic analyses, phylogenetic
      distribution and/or G + C content suggests that all the Thermotoga sp. strain RQ2
      specific sequences in the sequenced lambda clones have been acquired by lateral
      gene transfer. We suggest that the use of strain-specific small insert clones
      obtained by subtractive hybridization to target larger inserts for sequencing is
      an efficient, economical way to identify environmentally (or clinically) relevant
      interstrain differences and novel gene clusters, and will be invaluable in
      comparative genomics.

PMID- 14641595
TI  - Linking autotrophic activity in environmental samples with specific bacterial
      taxa by detection of 13C-labelled fatty acids.
AB  - A method for the detection of physiologically active autotrophic bacteria in
      complex microbial communities was developed based on labelling with the stable
      isotope 13C. Labelling of autotrophic nitrifying, sulphur-oxidizing and iron
      oxidizing populations was performed in situ by incubation with NaH[13C]O3.
      Incorporated label into fatty acid methyl esters (FAMEs) was detected and
      quantified using gas chromatography-mass spectrometry in single ion monitoring
      mode. Before the analyses of different environmental samples, the protocol was
      evaluated in pure culture experiments. In different environmental samples a
      selective labelling of fatty acids demonstrated which microbial taxa were
      responsible for the respective chemolithoautotrophic activity. The most strongly
      labelled fatty acids of a sample from a sulphide treating biofilter from an
      animal rendering plant were cis-7-hexadecenoic acid (16:1 cis7) and 11-methyl
      hexadecanoic acid (16:0 11methyl), which are as-yet not known for any sulphide
      oxidizing autotroph. The fatty acid labelling pattern of an experimental
      biotrickling filter sample supplied with dimethyl disulphide clearly indicated
      the presence and activity of sulphide-oxidizing bacteria of the genus
      Thiobacillus. For a third environmental sample from an acid mining lake sediment,
      the assignment of autotrophic activity to bacteria of the genus Leptospirillum
      but not to Acidithiobacillus could be made by this method, as the fatty acid
      patterns of these bacteria show clear differences.

PMID- 14641596
TI  - Indigenous and contaminant microbes in ultradeep mines.
AB  - Rock, air and service water samples were collected for microbial analyses from
      3.2 kilometres depth in a working Au mine in the Witwatersrand basin, South
      Africa. The approximately metre-wide mined zone was comprised of a carbonaceous,
      quartz, sulphide, uraninite and Au bearing layer, called the Carbon Leader,
      sandwiched by quartzite and conglomerate. The microbial community in the service
      water was dominated by mesophilic aerobic and anaerobic, alpha-, beta- and gamma
      Proteobacteria with a total biomass concentration approximately 10(4) cells ml(
      1), whereas, that of the mine air was dominated by members of the Chlorobi and
      Bacteroidetes groups and a fungal component. The microorganisms in the Carbon
      Leader were predominantly mesophilic, aerobic heterotrophic, nitrate reducing and
      methylotrophic, beta- and gamma-Proteobacteria that were more closely related to
      service water microorganisms than to air microbes. Rhodamine WT dye and
      fluorescent microspheres employed as contaminant tracers, however, indicated that
      service water contamination of most of the rock samples was < 0.01% during
      acquisition. The microbial contaminants most likely originated from the service
      water, infiltrated the low permeability rock through and accumulated within
      mining-induced fractures where they survived for several days before being mined.
      Combined PLFA and terminal restriction fragment length profile (T-RFLP) analyses
      suggest that the maximum concentration of indigenous microorganisms in the Carbon
      Leader was < 10(2) cells g(-1). PLFA, 35S autoradiography and enrichments suggest
      that the adjacent quartzite was less contaminated and contained approximately
      10(3) cells gram(-1) of thermophilic, sulphate reducing bacteria, SRB, some of
      which are delta-Proteobacteria. Pore water and rock geochemical analyses suggest
      that these SRB's may have been sustained by sulphate diffusing from the adjacent
      U-rich, Carbon Leader where it was formed by radiolysis of sulphide.

PMID- 14641597
TI  - Cell density related H2 consumption in relation to anoxic Fe(0) corrosion and
      precipitation of corrosion products by Shewanella oneidensis MR-1.
AB  - In the absence of oxygen, a protective H2 film is formed around an Fe(0) surface,
      inhibiting the electron flow from this surface. Our study of anoxic corrosion of
      Fe(0) beads revealed that, in the presence of Shewanella oneidensis MR-1, H2
      removal and precipitation of Fe mineral particles on the cell surface are
      determining processes for corrosion. These two biologically mediated processes
      were governed by cell density. H2 removal by Shewanella oneidensis was detected
      at cell concentrations of 1.0 x 10(6) live cells ml-1 and higher and H2 was
      electron donor for denitrification of NO3-. The removal of the protective H2
      layer from Fe(0) beads by Shewanella oneidensis, resulted in an increase of Fe
      release out of the Fe(0) beads from 153 +/- 25 mg l(-1) to 196 +/- 7 mg l-1 after
      20 h. When the cell concentration exceeded 1.0 x 10(8) live cells ml-1,
      precipitation of iron minerals on the cell surface was characteristic for the
      greatest percentage of MR-1 cells, whereas micrometre-scale iron precipitates not
      associated with culturable cell biomass significantly decreased in number.
      Addition of supernatant of a corrosion assay with high cell concentration induced
      metabolic activity in a corrosion assay with low cell concentration, resulting in
      increased H2 consumption and Fe release from Fe(0) beads. Homoserine lactone-like
      molecules were detected in the supernatant by a bio-assay, suggesting the
      involvement of a quorum-sensing regulatory mechanism.

PMID- 14641598
TI  - Experimental epizootiology of Zoophthora anhuiensis (Entomophthorales) against
      Myzus persicae (Homoptera: Aphididae) with a description of a modified Gompertz
      model for aphid epizootics.
AB  - Epizootiological features of Zoophthora anhuiensis, a fungal pathogen specific to
      aphids in southern China, were studied in six aptera colonies of Myzus persicae
      at 16 regimes of temperature (T = 10, 15, 20 and 25 degrees C) and relative
      humidity (H = 90%, 95%, 98% and 100% RH) with initially infected proportion (Ip)
      of 0.5 in experiment (Expt) 1 or at a fixed regime of 15 degrees C and 100% RH
      with a variable Ip of 0.17-1.00 in Expt 2. Mycosis-caused mortalities (Mp) varied
      with aphid densities (D) over time after colony initiation (t) were well fitted
      to a Gompertz growth model modified to include the variables T, H, Ip and D in
      the form of Mp = 91.72exp[-5.282exp[-(0.0095T + 0.0128H/T-0.5407D2/H)t]] for Expt
      1 (r2 = 0.94) or Mp = 95.49exp[-4.314exp[-(0.1479Ip + 0.1636/D)t]] for Expt 2 (r2
      = 0.97). These variables were effective in determining the rate of epizootic
      development in the M. persicae colonies. Based on the observed and fitted
      results, Z. anhuiensis was most adaptive to cool climate or season and
      epizootiologically was subject to a minimal effect of RH at an optimum of
      approximately 15 degrees C. However, the humidity became determinant for
      epizootic progress at higher temperatures. Interactive effects of the variables
      and application of the fitted models for predicting epizootic development in
      field situations are discussed.

PMID- 14641599
TI  - Phylogenetic analysis of the microbial populations in the wild herbivore
      gastrointestinal tract: insights into an unexplored niche.
AB  - At present, there is little information on the phylogenetic diversity of
      microbial species that inhabit the gastrointestinal tracts of wildlife. To
      increase understanding in this area, we initiated a characterization of the
      bacterial diversity in the digestive tracts of three wild African ruminant
      species namely eland (Taurotragus oryx), Thompson's gazelle (Gazella rufifrons)
      and Grant's gazelle (Gazella granti), together with a domesticated ruminant
      species, zebu cattle (Bos indicus), and a non-ruminant species, zebra (Equus
      quagga). Bacterial diversity was analysed by PCR amplification, sequencing and
      phylogenetic analysis of 16S ribosomal DNA (rDNA) sequences. A total of 252 full
      length 16S rDNA sequences averaging 1,500 base pairs (bp) in length, and an
      additional 27 partial sequences were obtained and subject to phylogenetic
      analysis. Using a 98% criterion for similarity, all except for one of the
      sequences were derived from distinct phylotypes. At least 24 distinct operational
      taxonomic units (OTU's) could be identified, with the majority of these sequences
      representing hitherto uncharacterized species and genera. The sequences were
      generally affiliated with four major bacterial phyla, the majority being members
      of the Firmicutes (low G+C Gram-positives) related to the genera Clostridium and
      Ruminococcus. By contrast, with earlier studies using 16S rDNA sequences to
      assess biodiversity in Bos taurus dairy cattle, Gram-negative bacteria in the
      Bacteroidales (Prevotella-Bacteroides group) were poorly represented. The lack of
      redundancy in the 16S rDNA dataset from the five African ungulate species, and
      the presence of novel sequences not previously described from the
      gastrointestinal tract of any animal species, highlights the level of diversity
      that exists in these ecosystems and raises the question as to the functional role
      of these species in the gastrointestinal tract.

PMID- 14641601
TI  - Pediatric allergy training.

PMID- 14641603
TI  - Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children.
AB  - Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to
      allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces
      IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in
      the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non
      atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses
      can be observed in peripheral blood in both atopic and non-atopic asthmatic
      children but not in healthy control children. The aim of the present study was to
      determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma secretion induced from
      peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens
      (timothy, cat, birch, dog and house dust mite) in asthmatic children with and
      without sensitization. The study included 13 atopic asthmatic, 5 non-atopic
      asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with
      allergens and cytokine production was measured with enzyme-linked immunosorbent
      assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were
      more commonly observed in both atopic and non-atopic asthmatics than in controls.
      Children with atopic, but not non-atopic, asthma produced higher levels of
      allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more
      IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia
      associated IL-5 responses are induced by cat and dog allergen in both atopic and
      non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated
      only with atopic asthma, probably due to their IgE-inducing properties.

PMID- 14641604
TI  - Reduced IL-2-induced IL-12 responsiveness in atopic children.
AB  - Atopy may be associated with a reduced T-cell function particularly regarding
      maturation of T helper 1 (Th1) responses. We hypothesized that atopic children
      may have a reduced capacity to up-regulate the beta2 subunit of the interleukin
      12 (IL-12) receptor (IL-12Rbeta2, the signal-transducing component). The study
      included 38 children followed from birth to the age of 7 years. Twenty one had a
      cumulative history of atopic disease, whereas 17 had none. Sixteen out of 21
      children also had atopic symptoms within the past year (current), out of whom 10
      children had atopic airway symptoms. The expression of IL-12Rbeta2 mRNA was
      analyzed by quantitative real-time PCR and the secretion of interferon-gamma (IFN
      gamma), IL-5 and IL-10 was assessed by enzyme-linked immunosorbent assay (ELISA).
      Children with current atopic airway symptoms and high levels of total IgE up
      regulated IL-12Rbeta2 mRNA expression less than non-atopic children with low IgE
      levels after IL-2 stimulation. This was accompanied by a low IL-2- and IL-12
      induced IFN-gamma production, possibly reflecting the reduced capacity of atopic
      children to up-regulate the IL-12 receptor. As IL-2 is needed to initiate and
      sustain immune responses and IL-12 promotes Th1 responses, this may contribute to
      the Th2-skewed pattern in atopic children.

PMID- 14641605
TI  - Adenoidectomy during early life and the risk of asthma.
AB  - The objective of the study was to evaluate the risk of asthma in children who had
      undergone an adenoidectomy, an operation frequently performed on children with
      glue ear or recurrent otitis media. Two surveys were carried out, a nation-wide
      questionnaire returned by 483 individuals (survey A) and a survey of hospital
      discharge records involving 1616 children who had undergone an adenoidectomy and
      161 control children who had undergone probing of the nasolacrimal duct due to
      congenital obstruction (survey B). The questionnaire (survey A) showed that an
      adenoidectomy before the age of 4 years was associated with asthma (OR 3.19, 95%
      CI 1.25; 8.13) and with allergy to animal dust (OR 2.50, 95% CI 1.27; 4.95). In
      survey B, asthma diagnosis was retrieved from the national asthma register. It
      showed also that adenoidectomy at an early age was associated with an increased
      risk of asthma (OR 6.74, 95% CI 2.99; 15.2). There was an association between
      asthma and adenoidectomy, even before adenoidectomy had actually been performed.
      The risk of asthma was highest among children who had had adenoidectomy because
      of recurrent otitis media. The observed association between an adenoidectomy and
      asthma may be explained by an underlying factor predisposing to both recurrent
      otitis media and asthma.

PMID- 14641606
TI  - Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants.
AB  - Respiratory infections in infancy may protect against developing Th2-mediated
      allergic disease (hygiene hypothesis). To estimate the relative contribution of
      particular viruses to the development of the immune system and allergic disease,
      we investigated longitudinally the prevalence of respiratory viral infections in
      infants. One hundred and twenty-six healthy infants were included in this
      prospective birth cohort study in their first year of life. Physical examination
      was performed and nasal brush samples were taken during routine visits every 6
      months and during an upper respiratory tract infection (URTI) (sick visits). The
      prevalence of respiratory viral infections in infants with URTI, infants with
      rhinitis without general malaise and infants without nasal symptoms was studied.
      Rhinovirus was the most prevalent pathogen during URTI and rhinitis in 0- to 2
      year-old infants ( approximately 40%). During URTI, also respiratory syncytial
      virus ( approximately 20%) and coronavirus ( approximately 10%) infections were
      found, which were rarely detected in infants with rhinitis. Surprisingly, in 20%
      of infants who did not present with nasal symptoms, rhinovirus infections were
      also detected. During routine visits at 12 months, a higher prevalence of
      rhinovirus infections was found in infants who attended day-care compared with
      those who did not. We did not observe a relation between breast-feeding or
      smoking by one or both parents and the prevalence of rhinovirus infections. The
      parental history of atopy was not related to the prevalence of rhinovirus
      infection, indicating that the genetic risk of allergic disease does not seem to
      increase the chance of rhinovirus infections. In conclusion, rhinovirus infection
      is the most prevalent respiratory viral infection in infants. It may therefore
      affect the maturation of the immune system and the development of allergic
      disease considerably.

PMID- 14641607
TI  - Mold-specific immunoglobulin G antibodies in a child population.
AB  - The determination of immunoglobulin G (IgG) antibodies to molds has been used as
      an objective evidence of significant mold exposure. Until present, no data have
      been published on antibody responses to molds in healthy children living in
      normal housing conditions. The microbe-specific IgG antibody concentrations of 21
      molds and 3 actinobacteria were determined by enzyme-linked immunosorbent assay
      (ELISA) in 103 1- to 6-year-old children (12.4% of the population of that age),
      and in 111 7- to 14-year-old school children (12.1%). The international standard
      sera were available, and the IgG concentrations of the test sera could be
      expressed in mg/l. On average, IgG concentrations increased in relation to age
      until the age of 6-7 years. At school age the increase still continued but more
      slowly. Actinobacteria were the only exceptions; all three tested strains
      Sreptomyces albus, S. griseus and S. halstedii resulted in rather high
      concentrations until 3 years of age. If the children lived in a farm, mold
      specific IgG concentrations increased at an earlier age than in other children.
      The results between farmers' children and other children differed significantly
      before school age for 20 of the 24 microbes tested, the four exceptions being the
      3 actinobacteria and the mold Aspergillus versicolor. The reference values must
      be age related, and separate references are needed for farmers' children before
      school age.

PMID- 14641608
TI  - Assessment of quality of life in children with peanut allergy.
AB  - Children with a peanut allergy (PA) are faced with food and social restrictions
      due to the potentially life-threatening nature of their disease, for which there
      is no cure or treatment. This inevitably impacts upon their quality of life
      (QoL). QoL of 20 children with PA and 20 children with insulin-dependent diabetes
      mellitus (IDDM) was measured using two disease-specific QoL questionnaires
      (higher scores correspond to a poorer QoL). One questionnaire was designed by us
      and the other was adapted from the Vespid Allergy QoL questionnaire. We gave
      subjects cameras to record how their QoL is affected over a 24-h period. Response
      rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA
      and IDDM subjects, respectively. Children with a PA reported a poorer quality of
      life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40
      for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (p</=0.001) in
      questionnaire 2. PA children reported more fear of an adverse event and more
      anxiety about eating, especially when eating away from home. Photographs fell
      into seven common categories: food, management, environment, away from home,
      physical activities, restaurant and people. Most photographs related to food and
      management issues and revealed difficulties for both groups regarding food
      restrictions. PA subjects felt more threatened by potential hazards within their
      environment, felt more restricted by their PA regarding physical activities, and
      worried more about being away from home. However, they felt safe when carrying
      epinephrine kits and were positive about eating at familiar restaurants. The QoL
      in children with PA is more impaired than in children with IDDM. Their anxiety
      may be considered useful in some situations, promoting better adherence to
      allergen avoidance advice and rescue plans.

PMID- 14641609
TI  - Bronchial hyper-responsiveness and atopy in urban, peri-urban and rural South
      African children.
AB  - Twenty years ago, the prevalence of atopic sensitization and bronchial hyper
      responsiveness (BHR) in Xhosa children in a rural location in South Africa was
      very low. The aim of this study was to document the current prevalence of these
      two indices by comparing traditional rural Xhosa children, recently urbanized
      Xhosa children and established city white children, and to consider factors that
      may account for the observed increase in all of these groups. One thousand four
      hundred and fifty-seven school children aged 10-14 years from the rural Transkei,
      from a recently urbanized peri-urban area and from urban Cape Town areas were
      studied using a questionnaire. Four hundred and eighteen children had histamine
      challenges, and 492 tests for atopy were also conducted. As determined by
      bronchial challenge with histamine, 17% of rural and 34.4% of recently urbanized
      Xhosa children had increased BHR, a marked increase from the 0.03% and 3.17%
      prevalence of increased BHR previously found using the exercise challenge. The
      prevalence of increased BHR in white urban children was 33%. Sensitization to one
      or more aero-allergens, as indicated by CAP RAST tests, was present in 36.6% of
      the rural Xhosa children with normal BHR and in 62.5% of those with increased
      BHR, a striking increase from that of previous studies. Atopic sensitization to
      one or more aero-allergens, as indicated by a skin prick test (SPT), was found in
      42.3% of the recently urbanized Xhosa children and 45% of urbanized white
      children. We have also documented sensitization to house dust mites in the rural
      Xhosa children for the first time. Passive cigarette smoking was not identified
      as a risk factor for increased BHR or atopy. Wood smoke in the indoor environment
      did not play a role in the rural Xhosa children's BHR. Ascaris infection does not
      appear to play any modifying role in the development of increased BHR in the
      rural or urban children. We have found that increases in BHR in the rural and
      recently urbanized Xhosa children develop independently of increases in atopy.
      Our results challenge the 'hygiene' hypothesis as a complete explanation for the
      recent dramatic worldwide increases in allergic diseases.

PMID- 14641610
TI  - Low-dose theophylline in childhood asthma: a placebo-controlled, double-blind
      study.
AB  - Regular anti-inflammatory treatment is essential in treating persistent asthma.
      Most commonly, inhaled corticosteroids (ICS) are used. However, especially in
      children, there is concern about the long-term safety of ICS such that doses
      should be kept to a minimum. The use of theophylline has decreased because of
      frequent side-effects in therapeutic doses. In adults, there have been reports
      about an immunomodulatory effect of low-dose theophylline. To study the clinical
      and immunomodulatory effect in children, 36 patients (mean age 12.5 SD 2.4 years)
      with moderate, persistent asthma on regular ICS were recruited into a placebo
      controlled, double-blind study. After a 6-week run-in period, patients received
      either theophylline 10 mg/kg bodyweight or placebo for 12 weeks. Diary cards,
      lung function, peripheral blood lymphocyte subpopulations and serum eosinophil
      cationic protein (sECP) were assessed. In the treatment group, mean serum
      theophylline was 7.1 mg/l. There was no change in symptoms or use of rescue
      medication. Mean (SD) peak expiratory flow (PEF) increased from 86% (24) to 95%
      (18) predicted. sECP decreased from 43.2 microg/l (32.5) to 26.5 microg/l (16.9)
      (p = 0.02). Lymphocyte subpopulations did not change. The study failed to show a
      beneficial clinical or an immunomodulatory effect of theophylline when used in
      low doses. These results do not support a more important role of theophylline in
      the long-term treatment of moderate childhood asthma.

PMID- 14641611
TI  - Urinary leukotriene E4 levels in children with allergic rhinitis treated with
      specific immunotherapy and anti-IgE (Omalizumab).
AB  - Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal
      anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral
      leukocytes stimulated with allergen in children with allergic rhinitis undergoing
      allergen immunotherapy. The aim of this study was to investigate the effect of
      anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene
      E4 (LTE4) levels. Children and adolescents with sensitization to birch and grass
      pollens and suffering from seasonal allergic rhinitis were included in a phase
      III, placebo-controlled, multicenter clinical study. Within the four-arm study,
      patients were randomized to receive SIT for either birch or grass pollen and to
      receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen
      season. From a total population of 225 children, we collected three urine samples
      in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range 7.2
      17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n = 9):
      SIT (grass or birch) + placebo]. Urine samples were collected before, during and
      at the end of treatment. Endogenous urinary LTE4 was separated by high
      performance liquid chromatography (HPLC) and determined by enzyme immunoassay
      with a specific antibody. No differences in urinary LTE4 concentrations were
      observed between the anti-IgE and the placebo groups before (A: 35.2; B: 36.5
      nmol/mol creatinine), during (A: 27.0; B: 29.3) and after treatment (A: 28.9; B:
      26.5 nmol/mol creatinine). We conclude that urinary LTE4 levels are not helpful
      in monitoring patients treated with anti-IgE and SIT.

PMID- 14641612
TI  - Cumulative prevalence of atopic eczema and related skin symptoms in a well-baby
      clinic: a retrospective cohort study.
AB  - The aim of the study was to assess the frequency and treatment policy of atopic
      eczema (AE) and related skin symptoms including rash, redness, dryness and itch
      in 0- to 5-year-old children. Health records of 320 children born in 1994 were
      systematically studied. The main results were that 77% of children suffered from
      skin symptoms during their first 5 years while the cumulative prevalence of AE
      was 16%, and 11% of children with skin symptoms were referred to a specialist. AE
      and related skin symptoms were common in the first 5 years of life, and were
      mostly temporary and responsive to topical treatment. Well-baby clinics play a
      key role in the treatment of skin-symptomatic children.

PMID- 14641613
TI  - Management of an anaphylactoid reaction to methotrexate with a stepwise graded
      challenge.
AB  - We report the management of a 15-year-old boy with an anaphylactic or
      anaphylactoid response to his first dose of methotrexate during induction therapy
      for acute lymphoblastic leukemia (ALL). Because weekly methotrexate therapy is an
      important component of continuation chemotherapy for pediatric ALL, a stepwise
      graded challenge was employed to achieve drug tolerance.

PMID- 14641614
TI  - Asthma-like syndrome in a teenager.

PMID- 14641616
TI  - Development and evaluation of a one-tube seminested PCR assay for the detection
      and identification of Penicillium marneffei.
AB  - A one-tube seminested polymerase chain reaction (PCR) assay was developed to
      detect and identify Penicillium marneffei DNA coding for 18S rRNA both from
      purified DNA and from clinical samples. DNA from 120 strains of organisms and 19
      blood samples from AIDS patients was amplified with F3, CPL1 and PM primers.
      Under optimized conditions, these primers detected 100% specifically amplified
      products of 251 and 331 bp from all P. marneffei DNA preparations (47 strains)
      and from two blood samples of AIDS patients suspected to suffer from
      penicilliosis marneffei. The assay was sensitive to detect as little as 10 pg
      purified DNA, which is equivalent to 250 cells. This PCR assay might be useful as
      an alternative test, if a rapid diagnosis of penicilliosis marneffei is needed.

PMID- 14641615
TI  - Invasive fungal infections are responsible for one-fifth of the infectious deaths
      in children with ALL.
AB  - The following report will discuss in detail all lethal invasive fungal infections
      (IFI) that occurred in a group of 2021 children with acute lymphoblasic leukaemia
      (ALL). The German ALL-Berlin-Frankfurt-Muenster (BFM) study group is one of the
      largest cooperation for the treatment of childhood ALL. Between 1995 and 2000,
      2021 children with ALL received chemotherapy according to the German BFM 95
      protocols (ALL-BFM 95). This population was retrospectively screened, whether a
      lethal fungal infection occurred: totally, in this group, 43 of 2021 (2.1%)
      children died because of infections. Nine of 43 (21%) patients died in the
      context of an IFI: six fatal Aspergillus infections and three fatal yeast
      infections were reported. The following report will focus on the nine children
      with ALL who died from IFI. The underlying risk factors (RF) included neutropenia
      (seven of nine patients) and steroid medication (nine of nine patients). Seven of
      nine children had additional medical complications (e.g. liver failure,
      haemolytic uraemic syndrome and acute renal failure). In six of nine children the
      fungal infection was progressive despite intravenous antimycotic therapy, three
      patients received no antifungal therapy, as IFI was not considered. The
      progression of IFI despite antimycotic therapy illustrates the inherent problems
      of diagnosis and the need for innovative therapeutic modalities. The high
      percentage (21%) of death from IFI among lethal infections in paediatric ALL
      patients illustrates the relevance of fungi in this group of patients. On the
      contrary, the total number of IFI in paediatric ALL patients remains to be
      determined, as only lethal infections were included in this report.

PMID- 14641617
TI  - Sinonasal aspergillosis in immunocompetent Indian children: an eight-year
      experience.
AB  - A retrospective study of 40 otherwise healthy children suffering from paranasal
      aspergillosis is presented. Fifteen percentage of this group was under 10 years
      of age. The clinical characteristics were marked facial deformity, orbital
      involvement (52.5%) and skull base erosion (12.5%). Ethmoid sinus was the
      commonest sinus to be affected. Aspergillus serology was positive in 35% and
      fungal culture grew the organism in 40%. Histopathology revealed allergic or non
      invasive fungal infections without any tissue invasions. Surgery was performed in
      all except one case. Recurrence was 15% treated by revision surgery and
      antifungal therapy.

PMID- 14641618
TI  - Prosthetic joint infections with osteomyelitis due to Candida albicans.
AB  - We report the case of a 78-year-old woman who suffered from a severe soft tissue
      and bone infection of her left knee 3 years after a total knee-joint replacement
      without loosening of her endoprosthesis. Cultures from joint aspiration and
      tissue specimen identified Staphylococcus aureus and Candida albicans. Direct
      microscopic examination of vital spongy bone and fibrous tissue revealed
      microabscesses and seeds of yeasts inside the fatty marrow and interface. After
      removal of the prosthesis several soft tissue and bone specimens were taken
      during planned re-operations. The histological examination showed no
      morphological changing, no reduction or extinction of the yeast cells under
      fluconazole therapy with a dosage of 6 mg kg(-1) body weight (400 mg daily).
      Curing of the fungal infection with eradication of the yeasts in the bony
      specimens was achieved with higher doses of 12 mg kg(-1) body weight (800 mg day(
      1)) over a 2 month regimen in combination with repeated surgical debridements.

PMID- 14641619
TI  - Performance of Bacticard Candida compared with the germ tube test for the
      presumptive identification of Candida albicans.
AB  - Bacticard Candida was compared with the germ tube test for the rapid, presumptive
      identification of Candida albicans. This test kit detects the enzymatic
      activities l-proline aminopeptidase and beta-galactosaminidase in yeast colonies
      grown on culture media. Candida albicans produces both enzymes whereas other
      yeasts produce only one or neither of the enzymes. We evaluated 536 isolates
      including eight genera and 33 species of medically important yeasts, including
      228 C. albicans and 36 C. dubliniensis. Both tests did not discriminate between
      C. albicans and C. dubliniensis isolates. The sensitivity and specificity for the
      Bacticard Candida test were 97.8 and 96.5%, respectively. Bacticard Candida and
      germ tube tests detected 246 (93.2%), and 256 (97%) C. albicans plus C.
      dubliniensis isolates. There were eight false-positive results with BactiCard
      Candida kit and four false-positive results with the germ tube test. Positive and
      negative predictive values for Bacticard Candida enzymatic test were 95.3 and
      98.4%, respectively, while 97.4 and 98.1% for the germ tube test, its specificity
      being 98.1% and efficiency 97% (97.7% for germ tube). We have observed slightly
      lower values of sensitivity and specificity than those reported by others using
      the BactiCard test kit. Bacticard Candida provides a rapid and accurate
      alternative to the germ tube test for the presumptive identification of C.
      albicans.

PMID- 14641620
TI  - In vitro cariogenic potential of Candida albicans.
AB  - The adherence and dissociation of Candida albicans, C. tropicalis, Streptococcus
      mutans and S. sanguis to six substrates including hydroxylapatite (HAP) which
      exhibit various hydrophobicity, was examined by the use of a bioluminescent
      adenosine triphosphate (ATP) assay. Dissolution of HAP by C. albicans or S.
      mutans was determined spectrophotometrically by the use of o-cresolphthalein
      complexone. In the adherence of C. tropicalis, S. mutans and S. sanguis, the
      amount of adherent cells correlated with the hydrophobicity of the substrates. In
      contrast, the adherence of C. albicans to HAP was extraordinary high, although
      the adherence of the fungi also correlated with the hydrophobicity of the
      substrates, except for HAP. The yeasts attached to HAP was effectively removed by
      high concentration of either phosphate or calcium ions. The amount of calcium
      release from HAP caused by C. albicans and S. mutans was 113 microg ml(-1) (final
      pH = 3.45), and 5.4 microg ml(-1) (final pH 4.81), respectively and the maximum
      growth of C. albicans and S. mutans was 10(7) cfu ml(-1) and 7.4 x 10(12) cfu ml(
      1), respectively. The results, taken together, suggest that C. albicans adhere to
      HAP specifically through electrostatic interaction, and that, in a much smaller
      number (1.0/7.4 x 10(5)), C. albicans possesses the ability to dissolve HAP to a
      greater extent (approximately 20-fold) when compared with S. mutans.

PMID- 14641621
TI  - Candida albicans strain carriage in patients and nursing staff of an intensive
      care unit: a study of morphotypes and resistotypes.
AB  - Candida albicans carriage of patients and nursing staff of an intensive care unit
      (ICU) was studied over an 8-month period. Swabs were taken at weekly intervals
      from multiple sites from patients. None of the patients had clinical Candida
      infection at the time of the first sampling. The hands and mouth of the nursing
      staff were sampled at fortnightly intervals. Of the 68 patients investigated for
      varying periods, 37 (54%) yielded C. albicans from one or more body sites,
      resulting in the isolation of 269 strains. Nosocomial acquisition of C. albicans
      was recorded in seven (19%) patients. The frequency of C. albicans isolation
      increased with extended stay in ICU. Sixteen of the 180 samples taken from hands
      and mouth of nursing staff, yielded C. albicans, 12 of which came from the mouth.
      Morphotyping of 88 randomly selected strains of C. albicans originating from 31
      patients yielded 34 morphotypes. There appeared to be no preference for any
      morphotype to colonize a particular anatomic site. Based on the susceptibility
      results, nine resistotypes were recognized. No correlation was apparent between
      any specific morphotype and resistotype patterns. The differences in morphotype
      and resistogram patterns of C. albicans isolates originating from same patients
      over a period of time suggest that some of the patients were colonized with more
      than one strain. Similarities in the morphotype and resistotype patterns of C.
      albicans strains isolated from patients and nursing staff tend to suggest
      possibility of exogenous acquisition.

PMID- 14641622
TI  - Genotyping of clinical Rhodotorula mucilaginosa isolates by pulsed field gel
      electrophoresis.
AB  - Identification and typing of fungal isolates is a prerequisite for control and
      prevention of nosocomial infections. As the discriminatory power of phenotypic
      methods is not sufficient for epidemiological purposes, genotyping methods such
      as DNA fingerprinting, random amplification of polymorphic DNA (RAPD) analysis,
      or pulsed field gel electrophoresis (PFGE) are preferred. To our knowledge, this
      study is the first application of PFGE for typing Rhodotorula mucilaginosa
      strains. The PFGE patterns of six clinical isolates produced two different
      karyotypes, which were confirmed by RAPD analysis. Five strains isolated from
      bloodstream infections from three different institutions showed the same
      karyotype and RAPD patterns, while the urological specimen differed slightly.

PMID- 14641623
TI  - Experimental evaluation of antifungal and antiseptic agents against Rhodotorula
      spp.
AB  - We studied the susceptibility of 21 strains of Rhodotorula rubra and nine strains
      of R. glutinis to eight antifungals and tested eight antiseptic agents on one
      strain of R. rubra. The tested strains were susceptible to ketoconazole, 5
      fluorocytosine, amphotericin B, and nystatin, intermediate to econazole and
      resistant to fluconazole, itraconazole and miconazole. After 5-min contact, six
      of the eight antiseptic agents tested showed a fungicidal activity on the tested
      R. rubra strain.

PMID- 14641624
TI  - High prevalence of foot diseases in Europe: results of the Achilles Project.
AB  - OBJECTIVE: To provide an insight into the prevalence of foot disease in Europe,
      and to include an assessment of the prevalence of predisposing factors and their
      correlation with foot disease. DESIGN: Large population-based survey conducted in
      16 European countries. SETTING: The project consisted of two parts (study I and
      study II), in which all patients presenting to general practitioners and
      dermatologists over a defined time period were invited to participate. Patients.
      In study I, 70,497 patients presenting to dermatologists or general practitioners
      were recruited, and in study II 19,588 patients presenting to dermatologists were
      recruited. MAIN OUTCOME MEASURE: The feet of all participants were examined for
      signs of foot disease. The assessors also recorded relevant details such as the
      age and sex of patients, and the presence of predisposing factors for foot
      disease. In addition, patients in study II were offered a free mycological
      examination of the toenails and skin on the feet. RESULTS: In study I, 57.0% of
      patients had at least one foot disease. In study II, 61.3% had at least one foot
      disease. The proportions of patients with fungal foot disease and non-fungal foot
      disease in study I were 34.9% and 38.4%, respectively, and in study II were 40.6%
      and 41.7%, respectively. Orthopedic conditions and metatarsal corns were the most
      frequently reported non-fungal foot diseases, and onychomycosis and tinea pedis
      were the most frequently observed fungal infections. CONCLUSIONS: This large
      scale survey suggests that the prevalence of fungal and non-fungal foot disease
      is higher than previously estimated.

PMID- 14641625
TI  - Action mechanisms of modern antifungal agents and resulting problems in the
      management of onychomycosis.
AB  - Successful treatment of onychomycosis in the infection site depends not only on
      achieving the minimal inhibitory concentration (MIC) of the antifungal agent,
      usually determined on fresh, proliferating fungal strains, but also on the
      effectivity against fungal spores dormant in nail keratin. Ciclopiroxolamine and
      terbinafine were investigated for their fungicidal properties against
      proliferating and dormant dermatophyte strains. While ciclopiroxolamine was 100%
      effective against Trichophyton mentagrophytes (50 microg ml(-1)) and Microsporum
      canis (5 microg ml(-1)) both in the proliferative and dormant phase after 5 days
      of incubation, the same result was achieved under identical test conditions with
      0.002 microg ml(-1) terbinafine using T. mentagrophytes as test organism in the
      proliferative and 2.0 microg ml-1 in the dormant phase. The terbinafine
      concentrations of 0.52 microg g(-1) measured in the nail are well below 2.0. This
      explains the high treatment failure and relapse rates observed under monotherapy
      of toenail onychomycosis even with modern antifungals. Consequently, combined
      therapy is recommended, beginning with atraumatic removal of the affected
      toenails and continuing with an antifungal nail lacquer combined with a systemic
      antifungal.

PMID- 14641626
TI  - Successful treatment of Acremonium fungemia with voriconazole.
AB  - We report two cases of Acremonium fungemia with proven involvement of the skin
      and probably of the lung in patients who were both undergoing chemotherapy, one
      for mantle cell lymphoma and the other for acute lymphoblastic leukemia. Both
      patients failed amphotericin B deoxycholate treatment and were successfully
      treated with voriconazole with very mild toxicity.

PMID- 14641627
TI  - Cutaneous sporotrichosis: an unusual clinico-pathologic and therapeutic
      presentation.
AB  - This report presents a number of unusual clinico-histopathologic and therapeutic
      features in a culture proven case of cutaneous sporotrichosis. These include
      lymphocutaneous sporotrichosis involving face; its dissemination in an otherwise
      healthy patient; its histology mimicking cutaneous cryptococcosis; two episodes
      of severe purulent inflammatory reaction bordering the lesion during therapy with
      saturated solution of potassium iodide; no therapeutic response to potassium
      iodide therapy and rapid healing of lesion with high-dose of fluconazole.

PMID- 14641628
TI  - Disseminated trichosporonosis in China.
AB  - A 20-year-old female patient presented with erythematous plaques on the nose
      which were progressively spreading to the trunk and the extremities, sometimes
      with erosions and scars. The patient was misdiagnosed as having seborrhoeic
      dermatitis and subacute cutaneous lupus erythematosus. The histopathological
      biopsy revealed mycotic infectious granuloma. Samples taken from skin lesions and
      other locations grew Trichosporon asahii in cultures. The identification was
      confirmed by molecular biological methods. The patient was treated successfully
      with liposomal amphotericin B in combination with fluconazole orally.

PMID- 14641629
TI  - Skin infection caused by Scedosporium apiospermum.
AB  - A woman with a skin infection because of Scedosporium apiospermum, in the
      interdigital spaces of her feet is presented. The minimum inhibition
      concentration values (MIC, microg ml(-1)) of this isolated mould for
      itraconazole, amphotericin B and terbinafine after 48 h were determined as 1, 8
      and 16, respectively. The patient was treated successfully with oral terbinafine
      and topical clotrimazole.

PMID- 14641632
TI  - Simulation in clinical learning.

PMID- 14641633
TI  - Setting up a clinical skills learning facility.
AB  - OBJECTIVE: This paper outlines the considerations to be made when establishing a
      clinical skills learning facility. CONSIDERATIONS: Establishing a clinical skills
      learning facility is a complex project with many possible options to be
      considered. A number of professional groups, undergraduate or postgraduate, may
      be users. Their collaboration can have benefits for funding, uses and promotion
      of interprofessional education. Best evidence and educational theory should
      underpin teaching and learning. The physical environment should be flexible to
      allow a range of clinical settings to be simulated and to facilitate a range of
      teaching and learning methods, supported by computing and audio-visual resources.
      Facilities should be available to encourage self-directed learning. The skills
      programme should be designed to support the intended learning outcomes and be
      integrated within the overall curriculum, including within the assessment
      strategy. Teaching staff may be configured in a number of ways and may be drawn
      from a variety of backgrounds. Appropriate staff development will be required to
      ensure consistency and quality of teaching with monitoring and evaluation to
      assure appropriate standards. Patients can also play a role, not only as passive
      teaching material, but also as teachers and assessors. Clinical, diagnostic and
      therapeutic equipment will be required, as will models and manikins. The latter
      will vary from simple part task trainers to highly sophisticated human patient
      simulators. Care must be taken when choosing equipment to ensure it matches
      specified requirements for teaching and learning. CONCLUSION: Detailed planning
      is required across a number of domains when setting up a clinical skills learning
      facility.

PMID- 14641634
TI  - Patient simulation for training basic and advanced clinical skills.
AB  - INTRODUCTION: Patient simulators are increasingly used in the education and
      training of healthcare professionals. This paper describes the history of human
      patient simulator development, the features of contemporary simulators, the
      acquisition of basic and advanced clinical skills using patient simulators, and
      the benefits, cost, limitations and effectiveness of this innovative learning
      modality. SIMULATOR DEVELOPMENT: The development of human patient simulators
      began in the late 1960s, and accelerated in the late 1980s and early 1990s.
      Several simulator systems are now professionally manufactured, commercially
      available, and used at hundreds of medical centres, universities and colleges in
      the USA and throughout the world. Contemporary patient simulators have many
      clinical features, and look and respond to interventions with ever-increasing
      degrees of realism because sophisticated physiological and pharmacological models
      automatically control many features. SIMULATOR USE IN MEDICAL EDUCATION:
      Simulators are used to teach basic skills, such as respiratory physiology and
      cardiovascular haemodynamics, and advanced clinical skills, e.g. management of
      difficult airways, tension pneumothorax, pulmonary embolism and shock. BENEFITS,
      COSTS AND LIMITATIONS: The simulation laboratory offers distinct educational
      advantages, especially for learning how to recognise and to treat rare, complex,
      clinical problems. Costs of simulator-based educational programmes include
      facility, equipment and personnel. Current limitations include clinical realism
      of the patient manikin and faculty development.

PMID- 14641635
TI  - Low- to high-fidelity simulation - a continuum of medical education?
AB  - CONTEXT: Changes in medical training and culture have reduced the acceptability
      of the traditional apprenticeship style training in medicine and influenced the
      growth of clinical skills training. Simulation is an educational technique that
      allows interactive, and at times immersive, activity by recreating all or part of
      a clinical experience without exposing patients to the associated risks. The
      number and range of commercially available technologies used in simulation for
      education of health care professionals is growing exponentially. These range from
      simple part-task training models to highly sophisticated computer driven models.
      AIM: This paper will review the range of currently available simulators and the
      educational processes that underpin simulation training. The use of different
      levels of simulation in a continuum of training will be discussed. Although
      simulation is relatively new to medicine, simulators have been used extensively
      for training and assessment in many other domains, most notably the aviation
      industry. Some parallels and differences will be highlighted.

PMID- 14641636
TI  - Development of foetal and neonatal simulators at the University of Porto.
AB  - BACKGROUND: Human error can be expected to play a significant role in adverse
      outcomes in perinatal acute care. In acute care of the adult, simulator based
      training is recommended and used to improve patient safety. AIMS: Our general
      goal is to develop model-driven foetal and neonatal educational simulators and
      curricula. The specific objectives of this paper are to introduce the reader to
      the perinatal acute care context and simulator design considerations, as well as
      to give initial results and describe ongoing developments. A brief description of
      adult simulators and simulation engines is followed by a more detailed
      description of a foetal distress simulator (FDS) and of models for a neonatal
      simulator developed at the University of Porto. Ongoing developments involve the
      modelling of foetal baroreflexes, the effect of uterine contractions, and an
      adapted method for estimating foetal heart rate variability parameters. RESULTS:
      We present FDS simulation results reflecting the changes in oxygen supply to the
      foetus and the foetal heart rate in response to a reduction in uterine blood
      flow. We also present a structural diagram of a model for the educational
      simulation of congenital heart disease and preliminary simulation results
      reflecting a patent ductus arteriosus. CONCLUSION: We expect that, after initial
      clinical and educational validation, the presented models and simulators will
      play a role in simulator-based educational programmes contributing to increased
      perinatal safety.

PMID- 14641637
TI  - Developing professional clinical skills for practice - the results of a
      feasibility study using a reflective approach to intimate examination.
AB  - OBJECTIVES: To develop a student-selected component (SSC) for junior medical
      students, to evaluate the feasibility of incorporating the development of skills
      in carrying out an intimate examination, whilst developing professional thinking
      skills using a reflective approach. SUBJECTS: The student selected component was
      designed for a maximum of 6 students over a 4-week period in Phase 2 (year 2 and
      3) of the undergraduate medical curriculum. SETTING: The Clinical Skills Centre,
      the Faculty of Medicine Nursing and Dentistry, University of Dundee, Scotland,
      UK. METHODS: The SSC consisted of a weekly patient clerking from the ward, an
      analysis of the clinical and communication skills for any intimate examinations
      the patient would require, and practice using simulators and simulated patients.
      Students were supported by timed periods of structured reflection, which enabled
      them to discuss ethical issues and their own professional conduct related to
      carrying out an intimate examination. The SSC was evaluated on 3 levels; student
      satisfaction, learning professional thinking using a reflective approach, and
      observing behaviour change in relation to skill development, using a ward
      simulation exercise. RESULTS: The evaluation at the levels of student
      satisfaction, learning professional thinking and changes in behaviour associated
      with intimate examination demonstrated that the SSC had been well received by the
      students, who felt they had improved their skills in intimate examinations in the
      context of a ward simulation exercise, in parallel with their professional
      thinking skills. CONCLUSION: It is possible to develop the professional thinking
      of junior medical students at the same time as developing their technical
      competence in relation to intimate examinations. It may be advantageous to
      introduce students early to this reflective approach, using simulation to promote
      the integration of theory with practice.

PMID- 14641638
TI  - Adoption and integration of simulation-based learning technologies into the
      curriculum of a UK Undergraduate Education Programme.
AB  - CONTEXT: At a time of significant changes in medical education world-wide, the
      international dimensions and global issues relating to the application of new
      learning technologies have been recognised. OBJECTIVE: The aim of this paper is
      to describe the adoption and integration within the curriculum in one United
      Kingdom (UK) medical school of 'Harvey', the Cardiology Patient Simulator, and
      the UMedic multimedia computer-based cardiology curriculum - resources developed
      in a medical school in the USA. PARTICIPANTS: The integration of the resources
      into the curriculum is described by 3 teachers actively involved in the
      cardiology curriculum of the UK medical school and 3 teachers associated with the
      development of resources in the USA. ASPECTS CONSIDERED: The review considers the
      adoption of Harvey and UMedic in the UK in programmes in relation to: curricular
      issues, training needs, learning outcomes, curriculum content and sequences of
      content, educational strategies, teaching and learning methods, assessment,
      communication about the curriculum and management of the curriculum. CONCLUSIONS:
      Learning resources, in the form of simulators and computer-based learning
      modules, developed in one country can be successfully adopted and implemented in
      another. Facets that facilitated the adoption included close liaison between the
      developers of the resources in the USA and the implementers in the UK, and
      careful and systematic planning including in-depth integration of the simulation
      based resources into the required curriculum rather than their relegation to a
      peripheral ad hoc position. The successful use of simulators such as Harvey
      requires the presence of a 'champion', a clinician educator and a supporting
      administrative staff who ensure the simulator's appropriate use.

PMID- 14641639
TI  - Learning the skills of flexible sigmoidoscopy - the wider perspective.
AB  - BACKGROUND: Nurse-led gastrointestinal endoscopy is a priority clinical area in
      the UK. Endoscopic procedures are challenging to learn, requiring a combination
      of technical competence (manipulating a flexible endoscope and interpreting the
      findings) and interpersonal skills (engaging effectively with a conscious patient
      who is frequently apprehensive). This paper explores the potential of an
      innovative, scenario-based approach which links a simulated patient with a
      computer-driven virtual reality (VR) training device for flexible sigmoidoscopy.
      Within this safe yet realistic quasi-clinical environment, learners carry out the
      procedure while interacting with the 'patient'. Communication skills are assessed
      by simulated patients, while quantitative performance data relating to the
      procedure is generated automatically by the VR simulator. METHODS: This pilot
      study took place within a nurse practitioner endoscopy course. A mixed
      methodology combined qualitative and quantitative data (observation and interview
      studies, communication rating scales and a range of computer-generated output
      measures from the VR simulator) in a multifaceted evaluation. RESULTS: Seven
      nurses took part in the study. Participants found the scenarios to be a
      convincing and powerful learning experience. All experienced high levels of
      anxiety. Simulated patients identified strengths in participants' communication
      skills, together with areas for development. Simulator-based practice led to an
      improvement in objective performance measures. DISCUSSION: Scenario-based
      training provides a powerful learning experience, allowing participants to build
      their technical expertise and apply it within a holistic clinical context without
      the risk of causing harm. We used this pilot study as a springboard for
      discussions over wider implications of procedure-based skills training, locating
      it within the literature on expertise and situated learning.

PMID- 14641640
TI  - Integrating human factors into the medical curriculum.
AB  - BACKGROUND: The study of human factors is a scientific discipline that deals with
      the interactions between human beings and the elements of a system. This is
      important because shortcomings in these areas, if unchecked, can result in
      adverse outcomes. Research into human factors in industries where safety is
      paramount has provided the basis of countermeasures against human error. Adverse
      outcomes in medicine resulting from human error exact a high cost in both patient
      suffering and financial outlay. CRM TRAINING: One of the approaches used to
      minimise the effect of human error is to train people in a set of knowledge,
      skills and attitudes that underpin the domain-specific competencies for that
      profession. These are referred to as non-technical skills (NTS). In aviation,
      such an approach has been shown to be both translatable from the training
      environment to the workplace and effective in reducing adverse outcomes.
      DISCUSSION: Medicine has incorporated this style of training, usually centred
      around simulator-based courses, but as yet in a piecemeal, episodic fashion which
      relies on participants volunteering to attend courses. Unlike other industries
      there is no systematic approach to linking the content of this teaching with the
      more conventional range of topics. As a consequence it is difficult to assess the
      impact of human factors training in medicine. This is partly because very little
      work has been done to date in identifying the key non-technical skills required
      in medicine, and the overall experience of workplace based assessment is limited.
      Lessons from other high reliability organisations may help to address the main
      challenges of developing the content, integrating it into the curriculum,
      reinforcing the concepts in the workplace through staff development and
      establishing its role in summative assessment.

PMID- 14641641
TI  - The use of clinical simulations in assessment.
AB  - CONTEXT: Simulation-based testing methods have been developed to meet the need
      for assessment procedures that are both authentic and well-structured. It is
      widely acknowledged that, although the authenticity of a procedure may be a
      contributing factor to its validity, authenticity alone never is a sufficient
      factor. AIM: In this paper we describe the mainstream development of various
      simulation-based approaches, with their strengths and weaknesses. The purpose is
      not to provide a review based on an extensive meta-analysis but to present
      crucial factors in the development of these methods and their implications for
      current and future developments. METHOD: The description of these simulation
      based instruments uses a subdivision according to the layers of Miller's pyramid.
      Written and computer-based simulations are aimed at measuring the 'knows how'
      layer, observation-based techniques such as standardised patient-based
      examinations and objective structured clinical examinations target the 'shows
      how' layer and performance practice measures assess performance at the 'does'
      layer. CONCLUSION: In all simulations, case specificity was found to pose the
      most prominent threat to reliability, while too much structure threatened to
      trivialise the assessment. The conclusion is that authentic and reliable
      assessment is predicated on a wise balance between efficiency and adequate
      content sampling.

PMID- 14641642
TI  - The quality of a simulation examination using a high-fidelity child manikin.
AB  - PURPOSE: Developing quality examinations that measure physicians' clinical
      performance in simulations is difficult. The goal of this study was to develop a
      quality simulation examination using a high-fidelity child manikin in evaluating
      paediatric residents' competence about managing critical cases in a simulated
      emergency room. Quality was determined by evidence of the reliability, validity
      and feasibility of the examination. In addition, the participants' responses
      regarding its realism, effectiveness and value are presented. METHOD: Scenario
      scripts and rating instruments were carefully developed in this study. Experts
      were used to validate the case scenarios and provide evidence of construct
      validity. Eighteen paediatric residents, 'working' as pairs, participated in a
      manikin-based simulation pre-test, a training session and a post-test. Three
      independent raters rated the participants' performance on task-specific technical
      skills, medications used and behaviours displayed. At the end of the simulation,
      the participants completed an evaluation questionnaire. RESULTS: The manikin
      based simulation examination was found to be a realistic, valid and reliable
      tool. Validity (i.e. face, content and construct) of the test instrument was
      evident. The level of inter-rater concordance of participants' clinical
      performance was good to excellent. The item analysis showed good to excellent
      internal consistency on all the performance scores except the post-test technical
      score. CONCLUSIONS: With a carefully designed rating instrument and simulation
      operation, the manikin-based simulation examination was shown to be reliable and
      valid. However, a further refinement of the test instrument will be required for
      higher stake examinations.

PMID- 14641644
TI  - New gene for CMT.

PMID- 14641645
TI  - Carpal tunnel syndrome and oral contraceptive drugs: risk or protective factor?

PMID- 14641646
TI  - Richard P. Bunge memorial lecture. Nerve injury and repair--a challenge to the
      plastic brain.
AB  - Repair and reconstruction of major nerve trunks in the upper extremity is a very
      challenging surgical problem. Today, there is no surgical repair technique that
      can assure recovery of tactile discrimination in the hand of an adult patient
      following nerve repair. In contrast, young individuals usually attain a complete
      recovery of functional sensibility. The outcome from nerve repair depends mainly
      on central nervous system factors including functional cortical reorganizational
      processes caused by misdirection in axonal outgrowth. Deafferentation due to
      local anesthetic block, amputation or nerve transection in the upper extremity
      leads to very rapid cortical synaptic remodeling, resulting in a distorted
      cortical hand representation as well as in enlarged and overlapping cortical
      receptive fields. Sensory relearning programs are aimed at refinement of these
      receptive fields to normalize the distorted hand map and improve processing at a
      high-order cortical level in the context of the 'new language spoken by the
      hand'. As peripheral nerve repair techniques cannot be further refined, there is
      a need for new and improved strategies for sensory relearning following nerve
      repair. We propose the utilization of multimodal capacity of the brain, using
      another sense (hearing) to substitute for lost hand sensation and to provide an
      alternate sensory input from the hand early after transection. The purpose was to
      modulate cortical reorganizations due to deafferentation to preserve cortical
      hand representation. Preliminary results from a prospective clinical randomized
      study indicate that the use of a Sensor Glove System, which stereophonically
      transposes the friction sound elicited by active touch, results in improved
      recovery of tactile discrimination in the nerve-injured hand. Future strategies
      for treatment of nerve injuries should promote cellular methods to minimize post
      traumatic nerve cell death and to improve axonal outgrowth rate and orientation,
      but high on the agenda are new strategies for refined sensory relearning
      following nerve repair.

PMID- 14641647
TI  - Mechanism of mitochondrial dysfunction in diabetic sensory neuropathy.
AB  - Symmetrical sensory polyneuropathy, the most common form of diabetic neuropathy
      in humans, is associated with a spectrum of structural changes in peripheral
      nerve that includes axonal degeneration, paranodal demyelination, and loss of
      myelinated fibers--the latter probably the result of a dying-back of distal
      axons. Mitochondrial dysfunction has recently been proposed as an etiological
      factor in this degenerative disease of the peripheral nervous system. Lack of
      neurotrophic support has been proposed as a contributing factor in the etiology
      of diabetic neuropathy based on studies in animal models of Type I diabetes. We
      have recently demonstrated that insulin and neurotrophin-3 (NT-3) modulate
      mitochondrial membrane potential in cultured adult sensory neurons. We therefore
      tested the hypothesis that diabetes-induced mitochondrial dysfunction is caused
      by impairments in neurotrophic support. We have used real-time fluorescence video
      microscopy to analyze mitochondrial membrane potential in cultured adult sensory
      neurons isolated from normal and diabetic rats. Diabetes caused a significant
      loss of mitochondrial membrane potential in all sub-populations of sensory
      neurons which can be prevented by in vivo treatment with insulin or NT-3. The
      mechanism of insulin and NT-3-dependent modulation of mitochondrial membrane
      potential involves the activation of the phosphoinositide 3 kinase (PI 3 kinase)
      pathway. Downstream targets of PI 3 kinase, such as Akt and the transcription
      factor cAMP response element-binding protein (CREB), are activated by insulin and
      NT-3 and regulate sensory neuron gene expression. These alterations in gene
      expression modulate critical components of metabolite pathways and the electron
      transport chain associated with the neuronal mitochondrion. Our results show that
      in adult sensory neurons, treatment with insulin can elevate the input of
      reducing equivalents into the mitochondrial electron transport chain, which leads
      to greater mitochondrial membrane polarization and enhanced ATP synthesis.

PMID- 14641648
TI  - Experimental strategies to promote functional recovery after peripheral nerve
      injuries.
AB  - The capacity of Schwann cells (SCs) in the peripheral nervous system to support
      axonal regeneration, in contrast to the oligodendrocytes in the central nervous
      system, has led to the misconception that peripheral nerve regeneration always
      restores function. Here, we consider how prolonged periods of time that injured
      neurons remain without targets during axonal regeneration (chronic axotomy) and
      that SCs in the distal nerve stumps remain chronically denervated (chronic
      denervation) progressively reduce the number of motoneurons that regenerate their
      axons. We demonstrate the effectiveness of low-dose, brain-derived neurotrophic
      and glial-derived neurotrophic factors to counteract the effects of chronic
      axotomy in promoting axonal regeneration. High-dose brain-derived neurotrophic
      factor (BDNF) on the other hand, acting through the p75 receptor, inhibits axonal
      regeneration and may be a factor in stopping regenerating axons from forming
      neuromuscular connections in skeletal muscle. The immunophilin, FK506, is also
      effective in promoting axonal regeneration after chronic axotomy. Chronic
      denervation of SCs (>1 month) severely deters axonal regeneration, although the
      few motor axons that do regenerate to reinnervate muscles become myelinated and
      form enlarged motor units in the reinnervated muscles. We found that in vitro
      incubation of chronically denervated SCs with transforming growth factor-beta re
      established their growth-supportive phenotype in vivo, consistent with the idea
      that the interaction between invading macrophages and denervated SCs during
      Wallerian degeneration is essential to sustain axonal regeneration by promoting
      the growth-supportive SC phenotype. Finally, we consider the effectiveness of a
      brief period of 20 Hz electrical stimulation in promoting the regeneration of
      axons across the surgical gap after nerve repair.

PMID- 14641649
TI  - Effects of FK506 on regeneration and macrophages in injured rat sciatic nerve.
AB  - Effects of FK506 [5.0 mg/kg body weight (BW), subcutaneous, daily] on nerve
      regeneration and presence of macrophages in lesioned rat sciatic nerves were
      studied. Models of autologous nerve graft or a nerve crush lesion were used and
      regeneration was evaluated by immunocytochemistry (also used to detect ED1/ED2
      macrophages) and sensory pinch reflex test, respectively. Treatment with FK506
      did not increase regeneration distance or regeneration rate in the autologous
      nerve grafts. However, regeneration distances after nerve crush were
      significantly longer following treatment with FK506. The number of macrophages
      (ED1/ED2) in nerve grafts increased over time, but treatment with FK506 had
      limited effects only in the presence of ED2 macrophages. Present and previously
      published studies may imply that there is a time-related and type-of-injury
      related profile of FK506's pro-regenerative effect.

PMID- 14641650
TI  - Digital electron microscopic examination of human sural nerve biopsies.
AB  - Diabetic peripheral polyneuropathy is characterized by axonal degeneration and
      regeneration as well as by Schwann cell and microvascular changes. These changes
      have been described at both the light (LM) and the electron microscopic (EM)
      levels; however, EM has not been applied to large clinical trials. Our goal was
      to adapt the rigorous techniques used for quantifying human biopsies with LM
      image analysis to accommodate ultrastructural analyses. We applied digital image
      capture and analysis to the ultrastructural examination of axons in sural nerve
      biopsies from diabetic patients enrolled in a multicenter clinical trial. The
      selection of sural nerve biopsies was based on the quality of specimen fixation,
      absence of physical distortion, and nerve fascicle size (> or =100,000; < or
      =425,000 microm2). Thin sections were collected on formvar-coated slot grids,
      stabilized with carbon and scanned on a Phillips CM100 transmission electron
      microscope. Digital images were captured with a Kodak Megaplus 1.6 camera. A
      montage was constructed using software derived from aerial mapping applications,
      and this virtual image was viewed by EM readers. Computer-assisted analyses
      included identification and labeling of individual axons and axons within
      regenerating clusters. The average density of regenerating myelinated axon
      clusters per mm2 was 65.8 +/- 5.1, range of 0-412 (n = 193). These techniques
      increase the number of samples that may be analyzed by EM and extend the use of
      this technique to clinical trials using tissue biopsies as a primary endpoint.

PMID- 14641651
TI  - Effects of gadolinium and tetrodotoxin on the response of slowly adapting type I
      mechanoreceptors to mechanical stimulation in frog dorsal skin.
AB  - To elucidate the excitatory mechanism of mechanoreceptors innervating the frog
      skin, we examined the effects of gadolinium (Gd3+) and tetrodotoxin (TTX) on the
      response of single-unit activity of slowly adapting type I mechanoreceptors to
      mechanical stimulation topically applied to the receptive field (RF). Recordings
      were made from 46 fibers responding to mechanical stimulation with von Frey
      hairs, which caused an irregular firing pattern with slow adaptation. Application
      of a mechanically gated channel blocker, Gd3+ (30 microM), and a Na+ channel
      blocker, TTX (3 microM), caused the suppression of discharge rates, which was
      characterized by the conversion of a slowly adapting to a rapidly adapting
      discharge pattern. The administration of a high-voltage-activated (HVA) Ca2+
      channel blocker, Cd2+ (100 microm), inhibited the unit discharge and caused the
      conversion of a slowly adapting to a rapidly adapting discharge pattern. Tonic
      discharges evoked by anodal electrical stimulation were inhibited by the
      application of Gd3+ or TTX. Electron microscopic examination showed that the
      cytoplasm of Merkel cells seen in the RF contained numerous Merkel granules.
      These results suggest that the excitatory mechanism of frog cutaneous
      mechanoreceptors may be mediated by the activation of Gd(3+)-sensitive stretch
      activated channels in the Merkel cell-neurite complex, which are related to the
      Na+ influx via voltage-gated Na+ channels and/or the Ca2+ influx through HVA Ca2+
      channels.

PMID- 14641652
TI  - Guidelines for the diagnosis and treatment of chronic inflammatory demyelinating
      polyneuropathy.

PMID- 14641655
TI  - The use of fluorescein-enhanced quantitative light-induced fluorescence to
      monitor de- and re-mineralization of in vitro root caries.
AB  - The use of fluorescein-enhanced quantitative light-induced fluorescence (QLF) in
      the detection of in vitro root caries demineralization and reminerlization was
      investigated. Fourteen previously extracted human premolar roots were selected
      and determined to be caries-free. Cementum was removed and nail varnish applied
      leaving an exposed window. Positive and negative controls were selected. During a
      demineralizing regimen, roots were removed at regular intervals (12, 48, 72 and
      120 h) and immersed in sodium fluorescein (0.2 mg L(-1)). Following gentle
      rinsing, each root was examined using QLF before being returned to the
      demineralizing solution. Following 120 h, each tooth was sectioned through the
      lesion and one-half retained for transverse micro radiography (TMR) analysis. The
      remaining half were subjected to a remineralizing regimen undergoing the same
      fluorescein and QLF examinations at 7, 28 and 36 days. Results showed that QLF
      effectively monitored demineralization/remineralization of root dentine as
      represented by fluorescein penetration. TMR analysis showed good correlations
      with QLF (DeltaZ/DeltaQ) after demineralization (r = 0.89) and remineralization
      (r = 0.84). The technique could represent an in vivo method for root caries
      detection and classification.

PMID- 14641656
TI  - Dimensional stability and dehydration of a thermoplastic polycarbonate-based and
      two PMMA-based denture resins.
AB  - This study compared the dimensional stability and dehydration of a thermoplastic
      polycarbonate denture base resin with two conventional polymethyl methacrylate
      denture base resins. Maxillary complete dentures were fabricated from the three
      denture materials and the accuracy of fit along the posterior palatal border of
      the cast used in processing was measured. Measurements were conducted at five
      palatal locations immediately after processing and at 7 and 30 days during
      immersion in water (23 degrees C) and at 7 and 30 days during dehydration (23
      degrees C, 65-75% relative humidity). Percentage mass loss during dehydration was
      determined with an electronic balance. The thermoplastic material was separately
      compared with each of the conventional resins using a modified Welch two-sample t
      test, with a Bonferroni correction for P values. For mean palatal dimensional
      change, the thermoplastic resin was generally not statistically different from
      the conventional resins after processing and during immersion (P > or = 0.06),
      but was generally less than the conventional resins during dehydration (P < or =
      0.02). For mean percentage mass loss, the thermoplastic resin consistently showed
      much smaller, statistically significant values compared with the conventional
      resins (P < 0.001). It was concluded that the thermoplastic resin should show
      dimensional changes in service comparable with the conventional resins, but less
      dimensional change caused by dehydration.

PMID- 14641657
TI  - Corrosion susceptibility of titanium covered by dental cements.
AB  - Titanium has become a material of great interest in prosthodontics in recent
      years because of its excellent biocompatibility, corrosion resistance and
      desirable physical and mechanical properties. In this study, we determined the
      influence of dental cements on the passivation of titanium. We developed
      experimental electrodes that associate titanium and dental cements. Polarization
      resistance of titanium electrodes has been determined for uncovered metal and
      electrodes covered with five different dental cements. Coverage with zinc
      eugenate led to more resistance to corrosion, but fluorinated composite such as
      glass-ionomer and zinc phosphate coverage increased the corrosion susceptibility.

PMID- 14641658
TI  - Reliability and temporal variation of masseter muscle thickness measurements
      utilizing ultrasonography.
AB  - Muscle thickness may now be measured in the clinic by ultrasonography. The
      purpose of this study was to test (i) whether the position of the transducer on
      the muscle affects muscle thickness measurements and (ii) whether measurements
      from identical locations vary over time. Muscle thickness of one masseter muscle
      side was measured in each of 30 volunteers. Measurements were recorded at five
      different locations on the lateral surface of each muscle. Four measurement
      sessions were performed, and two sets of measurements were recorded at each
      session. Spatial position of the transducer had a clear effect on the muscle
      thickness measurements (P < 0.0001). Measurements made at the most upper and
      middle level were less and greater (P < 0.0001), respectively, than those made at
      the upper, lower, and most lower levels. Measurements from various positions did
      not differ (P > 0.05) when made at the same level. Masseter thickness
      measurements recorded at a given site were consistent across all of the testing
      sessions (P=0.575). The data suggest that reliable interpretation of longitudinal
      measurements of masseter thickness obtained with ultrasonography requires
      accurate repositioning of the transducer. Ultrasonography may be used to
      investigate the effect of specific treatment modalities on masseter thickness
      measurements.

PMID- 14641659
TI  - Relationship between the craniofacial complex and size of the resorbed mandible
      in complete denture wearers.
AB  - A cephalometric study was conducted on 34 complete denture wearers to examine the
      relationship between the area of the mandible and the skeletal facial form, the
      area of the mandible and the gonial angle, and the area of the mandible and the
      length of the mandible. No significant correlation was found between the area of
      the mandible and the skeletal facial types or the gonial angle. A statistically
      significant correlation (P < 0.0028) was found between the length of the mandible
      and the area of the mandible. Residual resorption of the mandible appears to be
      independent of skeletal facial form and the gonial angle.

PMID- 14641660
TI  - In vitro comparison of the efficacy of Carisolv and conventional rotary
      instrument in caries removal.
AB  - The purpose of this in vitro study was to compare the efficacy of a new
      chemomechanical caries removal agent, Carisolv (MediTeam AB, Savedalen, Sweden),
      with conventional slow-speed rotary instrument (bur). Fourteen extracted human
      molar teeth with deep dentine caries and no enamel coverage were selected for the
      study. Their laser fluorescence values were over 30 (DIAGNOdent; KaVo, Biberach,
      Germany). After the teeth were sectioned through the centre of the carious
      lesion, one half was removed with conventional drilling (bur); the other half was
      removed with Carisolv gel. Removal of carious dentine was continued until the
      lesion was deemed caries-free by visual and tactile criteria. The preparation
      time for each caries removal technique was also noted. The two halves of each
      tooth were fixed in 10% buffered-formaldehyde for 1 week. They were then
      decalcified, dehydrated and embedded in paraffin blocks for histological studies.
      After taking serial sections of 5 microm thickness, sections were mounted on
      glass slides, deparaffinized, dehydrated and stained with toluidine blue for
      observation under a light microscope. Each section was examined for the presence
      of bacteria. Complete removal of caries was achieved in 13 (93%) of 14
      conventionally prepared teeth, and 5 (36%) of 14 chemomechanically prepared teeth
      (P < 0.05). Mean (+/-SD) time for caries removal was 272 s (+/-53.3) with
      Carisolv, and 116 s (+/-49.4) with drilling. The results of this study suggest
      that conventional rotary instrument (bur) was more effective than Carisolv in
      removal of carious tissue and also takes shorter time.

PMID- 14641661
TI  - Clinical evaluation of low-level laser therapy and fluoride varnish for treating
      cervical dentinal hypersensitivity.
AB  - The aim of this study was to evaluate in vivo the use of low-level galium
      aluminium-arsenide (GaAlAs) (BDP 600) laser and sodium fluoride varnish
      (Duraphat) in the treatment of cervical dentine hypersensitivity. Twelve
      patients, with at least two sensitive teeth were selected. A total of 60 teeth
      were included in the trial. Prior to desensitizing treatment, dentine
      hypersensitivity was assessed by a thermal stimulus and patients' response to the
      examination was considered to be a control. The GaAlAs laser (15 mW, 4 J/cm2) was
      irradiated on contact mode and fluoride varnish was applied at cervical region.
      The efficiency of the treatments was assessed at three examination periods:
      immediately after first application, 15 and 30 days after the first application.
      The degree of sensitivity was determined following predefined criteria. Data were
      submitted to analysis and no statistically significant difference was observed
      between fluoride varnish and laser. Considering the treatments separately, there
      was no significant difference for the fluoride varnish at the three examination
      periods, and for laser therapy, significant difference (P < 0.05) was found
      solely between the values obtained before the treatment and 30 days after the
      first application. It may be concluded that both treatments may be effective in
      decreasing cervical dentinal hypersensitivity. Moreover, the low-level GaAlAs
      laser showed improved results for treating teeth with higher degree of
      sensitivity.

PMID- 14641662
TI  - Validity of a laser fluorescence system (DIAGNOdent) for detection of occlusal
      caries in third molars: an in vitro study.
AB  - The aim of this study was to compare the validity of the measurements of the
      laser fluorescence device, KaVo DIAGNOdent, with the result of polarized light
      microscopy in the detection of occlusal fissure caries in extracted third molars.
      Ten impacted, surgically removed, and 25 extracted third molars with
      macroscopically intact occlusal surfaces were selected. The DIAGNOdent
      measurements of the occlusal test site were recorded by two observers at
      intervals of 2 days. The teeth were then sectioned at the specified test sites
      for histological examinations. Prepared specimens were evaluated under the
      polarized light microscopy and all images were scored with the caries
      classification of D1 (sound and fissure lesion in the half of the outer enamel),
      D2 (enamel decay) and D3 (dentin decay) level (gold standard). The kappa value
      for the inter-observer repeatability was calculated and the value 0.83 for the
      first measurements and 0.67 for the second measurement were
      obtained,respectively. Inter-observer correct classification percentages were
      88.5 and 77.1 for the first and second measurements, respectively. The kappa
      value for intra-observer repeatability was 0.79 for the first observer and 0.75
      for the second observer. Intra-observer correct classification percentage values
      were 85.7 and 82.8 for the first and second observer, respectively. Value of
      specificity for the detection of enamel caries at D1 level was 0.74 and
      sensitivity values at D2 and D3 levels were 0.66 and 1.00, respectively. The
      present study indicates that the DIAGNOdent provides not only almost perfect
      agreement but also sufficient repeatability at D1, D2, D3 levels and better
      specificity at D1 level as well as lower sensitivity at D2 level and excellent
      sensitivity at D3 level.

PMID- 14641663
TI  - The effect of the gonial angle, ramus length, age and gender on the
      temporomandibular opening index.
AB  - Linear mouth opening is often used to assess the limitation of mandibular
      movement. However, this has a number of limitations. It is dependent on variables
      such as age, gender and ramus length. A new measure of movement has been
      developed previously, called the temporomandibular opening index (TOI). Forty-two
      subjects who did not exhibit signs and symptoms of temporomandibular disorder
      (TMD) were recruited to this study. The relationship of age, gender, gonial
      angle, ramus length and the TOI was studied. Linear regression analysis showed
      that the TOI was not dependent on gender (P > 0.644), gonial angle (P > 0.327),
      ramus length (P > 0.248) and age (P > 0.690). The index may therefore be a better
      measure of mandibular movement.

PMID- 14641664
TI  - Symptoms and signs of temporomandibular disorders and oral parafunctions among
      Saudi children.
AB  - This study aimed to record the prevalence of signs and symptoms of
      temporomandibular disorders (TMD) and oral parafunctions among Saudi children. A
      questionnaire and a clinical examination of signs and symptoms of TMD were
      performed on 1940 stratified randomly selected schoolchildren. The sample was
      divided into three groups, 505 with primary, 737 with mixed and 734 with
      permanent dentition. The prevalence of TMD signs was found to be 20.7% and the
      most common sign of TMD was joint sounds (11.8%). The second most common sign was
      restricted mouth opening (5.3%). Muscle and temporomandibular joint (TMJ) pain as
      well as deviation upon jaw opening appeared infrequently. TMJ sounds were
      significantly increasing with age (P < 0.05). TMD symptoms as reported by the
      parents were evident in 24.2% of the returned questionnaires (1113). The most
      common symptoms were headache (13.6%) and pain on chewing (11.1%). The incidence
      of headache was found to be significantly increasing from primary to permanent
      dentition (P < 0.01). No sex difference in the prevalence of any symptom was
      reported. Nail biting was the most common oral parafunction (27.7%) while bruxism
      was the least common (8.4%). All parafunctions except bruxism were significantly
      related to age. Cheek biting and thumb sucking were reported more in females than
      in males. The importance of a screening examination for symptoms and signs of TMD
      should not be overlooked in the clinical assessment of the pediatric patient.

PMID- 14641665
TI  - Role of mastication and swallowing in the control of autonomic nervous activity
      for heart rate in different postures.
AB  - Mastication and swallowing increase the heart rate, and posture change and
      respiration also modulate the heart rate. To clarify the role of mastication and
      swallowing in the modulation of the autonomic nervous activity, we investigated
      how they interact with modulation of the heart rate by changing body positions
      and respiration in young healthy subjects. R-R intervals of electrocardiogram at
      rest were significantly changed with different body positions, compared with
      supine and standing. A net shortening by mastication of a chewing gum base was
      similar in various postures. Respiration induced a periodic change in the R-R
      intervals, depending on the body postures, but mastication did not markedly
      change them in each posture. Dry swallowing at rest and spontaneous swallowing
      during the mastication in the sitting position induced a similar transient
      shortening and suppressed the respiration-induced changes after the swallowing.
      The net transient shortening by dry swallowing at rest was similar in the
      different postures. These results suggest that signals from mastication and
      swallowing are summated with those from body positions and respiration for
      shortening the R-R intervals and that signals from swallowing suppress the
      respiration-induced periodic changes.

PMID- 14641666
TI  - Inhibition of demineralization in vitro around fluoride releasing materials.
AB  - Replacement of restorations because of secondary caries is a continuing problem
      in restorative dentistry. This investigation assessed the capacity of fluoride
      releasing restorative materials to resist caries in vitro when used in roots.
      Class 5 cavities were prepared in buccal and lingual surfaces of 30 extracted
      premolars and restored with one of three polyacid modified resin composites (F
      2000, Hytac and Compoglass F), a resin modified glass-ionomer cement (Fuji II LC)
      a conventional glass ionomer (Ketac-Fil), and a resin composite (Z-100). After 5
      weeks in an acid gel for caries-like lesion formation, the teeth were sectioned
      longitudinally and examined with polarized light. The results showed that
      restoration of caries with polyacid modified resin composites and resin modified
      glass ionomer cements may be of great importance in the prevention of secondary
      caries around the restorations in roots. Clinical Relevance Light cured fluoride
      releasing restorations may inhibit caries-like lesions. Inhibition of
      demineralization in vitro around fluoride releasing materials.

PMID- 14641668
TI  - Crown retention with use of different sealing systems on prepared dentine.
AB  - The purpose of this in vitro study was to evaluate crown retention after using
      different sealing systems on prepared dentine. Ca(OH)2 suspension was used in
      comparison with three adhesive bonding systems (Gluma Desensitizer, Optibond FL,
      Prompt L-Pop). Extracted human premolars were uniformly prepared with the use of
      a special parallelometer (11 degrees taper, 4 mm axial length). Groups of 20
      teeth each were treated with each sealing system. Then crowns were fabricated and
      temporarily cemented twice. Finally the abutments were cleaned and the crowns
      were cemented with a glass-ionomer cement Ketac-Cem. Subgroups of 10 crowns were
      removed with a universal testing machine following storage in distilled water
      either for 3 days or for 150 days. Prior to dislodging, the crowns of both groups
      were subjected to chewing simulation. The mean dislodgement stresses in MPa were
      between 4.9 and 6.9. A range test of Student-Newmann-Keuls revealed significant
      differences between Ca(OH)2 and Optibond FL (P < 0.05), while the storage time
      had no significant effect. The level of microleakage increased significantly with
      storage time (P < 0.05). It is concluded, that the use of Gluma Desensitizer and
      Prompt L-Pop did not affect crown retention as compared with Ca(OH)2, thus may be
      used in combination with glass-ionomer cement to desensitize prepared teeth.

PMID- 14641669
TI  - Pressure-pain threshold of oral mucosa and its region-specific modulation by pre
      loading.
AB  - Once subjected to denture wearing, oral mucosa has to withstand mechanical loads
      of various levels and durations. However, how this load affects oral mucosal
      sensitivity is unknown. This study investigated the pressure-pain threshold (PPT)
      of oral mucosa with or without pre-loading. An electric pressure algometer was
      developed specifically for measuring the PPT of oral mucosa. Measurements of 10
      dentulous maxillae showed that the baseline PPT (BPPT) of the palatal site was
      4.9- and 3.7-fold greater than that of the labial or buccal sites, respectively.
      The PPT of the labial site decreased significantly compared with its BPPT after 2
      s-100% BPPT and 5 s-100% BPPT pre-loading. The PPT of the palatal site increased
      after 5 s-50% BPPT and 5 s-80% BPPT and 0.2 s-100% BPPT and 2 s-100% BPPT pre
      loading. The PPT of the buccal site did not change after all levels and durations
      of pre-loadings tested. These results indicated the disproportionate modulation
      of oral mucosal PPT following various loads, suggesting that oral mucosa
      possesses region-specific psychophysical tolerance to mechanical stimuli.

PMID- 14641670
TI  - Association between condylar position, joint morphology and craniofacial
      morphology in orthodontic patients without temporomandibular joint disorders.
AB  - The present study investigated condylar position and joint morphology in
      adolescent patients and elucidated the possible association between the joint
      structure and condylar position, and craniofacial morphology. Sixty-five
      adolescent patients were selected as subjects and their tomograms and lateral
      cephalograms were analysed. No significant differences in joint spaces were found
      between the right and left temporomandibular joints. Both the condyles in this
      population were located slight anteriorly in the glenoid fossa. With respect to
      the association between condylar position, joint morphology and craniofacial
      morphology, the ramus plane angle also exhibited significant negative
      correlations with posterior, lateral and medial joint spaces. Furthermore, there
      was a significant negative correlation between the gonial angle and the anterior
      joint space. These findings imply that the condyle was likely to show more
      posterior position in the glenoid fossa when the mandible exhibited clockwise
      rotation. In conclusion, the condyle in the adolescent subjects showed a
      symmetrical anterior position relative to the glenoid fossa. In addition, the
      joint spaces and it ratios were significantly related to the craniofacial
      morphology associated with vertical dimension. It is suggested that the condylar
      position may be affected by craniofacial growth pattern.

PMID- 14641671
TI  - Influence of liquid temperature and flow rate on enamel erosion and surface
      softening.
AB  - Enamel erosion and softening are based on chemical processes which could be
      influenced by many factors including temperature and acid flow rate. Knowledge of
      the influence of these variables could have relevance to research experiments and
      clinical outcomes. Both parameters were investigated using an ultrasonication and
      profilometry method to assess erosion depth and surface softening of enamel. The
      influence of temperature was studied by eroding polished human enamel samples at
      4, 20, 35 or 50 degrees C for 2 h. Secondly, different liquid flow conditions
      were established by varying acid agitation. Additionally, a slow laminar flow and
      a jet of citric acid, to simulate drinking through a straw, were applied to
      specimens. Erosion depth increased significantly with acid temperature from 11.0
      microm at 4 degrees C to 35.8 microm at 50 degrees C. Surface softening increased
      much more slowly and plateaued at 2.9 microm to 3.5 microm after 35 degrees C. A
      strong dependence of erosion on liquid flow was revealed. In unstirred conditions
      only 8.6 microm erosion occurred, which increased to 22.2 microm with slow
      stirring and 40.9 microm with fast stirring. Surface softening did not increase
      correspondingly with its largest extent at slow stirring at 3.4 microm.The
      implication of these data are: first, the conditions for erosion experiments in
      vitro or in situ need to be specified for reliable comparisons between studies.
      Secondly, erosion of teeth by soft drinks are likely to be influenced both by the
      temperature of the drink and individual drinking habits.

PMID- 14641672
TI  - Plasma treatment increased shear bond strength between heat cured acrylic resin
      and self-curing acrylic resin.
AB  - Self-curing acrylic resin is generally used for the repair of a fractured denture
      base. However, re-fracture of the repaired denture base resin often occurs
      because of poor bonding strength between the base resin and self-curing repair
      resin. The effect of plasma treatment on the shear bond strength between heat
      cured acrylic resin and the self-cured acrylic was examined. It was revealed that
      plasma irradiation is effective in increasing the shear bond strength. Plasma
      irradiation does not cause environmental pollution, as it does not require
      chemicals. It is a useful method to increase adhesive strength between heat cured
      acrylic resin and self-curing acrylic resin.

PMID- 14641673
TI  - Effects of chemical disinfectants on the transverse strength of denture base
      acrylic resins.
AB  - The disinfection of dental prostheses by immersion in a chemical solution should
      be capable of rapid inactivation of pathogenic microorganisms, without causing
      any adverse effect on the denture base resins. This study evaluated the effect of
      disinfection immersion on the transverse strength of two heat-cured resins. The
      denture base resins (Lucitone 550 and QC 20) were polymerized according to the
      manufacturers' instructions. After polymerization, the specimens were polished,
      and then stored in water at 37 degrees C for 50 +/- 2 h prior immersion in one of
      the following solutions for 10 min: 4% chlorhexidine, 1% sodium hypochlorite and
      3.78% sodium perborate. The specimens were submitted to disinfection twice,
      simulating when dentures come from the patient and before being returned to the
      patient. Ten specimens were made for each group. The transverse strength was
      evaluated by a 3-point bend test. The flexural strength of the two denture base
      acrylic resins evaluated remained unaffected after immersion in the three
      solutions evaluated. In general, the QC 20 resin specimens exhibited lower
      transverse strength than the Lucitone 550 resin specimens, regardless of
      immersion solutions.

PMID- 14641674
TI  - Effect of fluorosis on dentine shear bond strength of a self-etching bonding
      system.
AB  - The purpose of this study was to investigate the effect of dental fluorosis on
      shear bond strength of a composite material to dentine. Forty human premolar
      teeth were classified according to the severity of fluorosis using the Thylstrup
      and Fejerskov index and were divided into four groups (TFI scores of 0, 3, 4 and
      5) of 10 teeth. Non-fluorosed teeth (TFI score of 0) served as the control group.
      A self-etching light-cured bonding system, Clearfil SE Bond, and a micro-hybrid
      light-cured composite, Clearfil AP-X were selected for the study. Buccal surfaces
      of mounted teeth were ground flat to expose the dentine. Composite cylinders, 4
      mm diameter and 4 mm length, were bonded to the treated dentine surfaces. Shear
      bond strength was measured with an universal testing machine at a cross-head
      speed of 0.5 mm min-1. After failure, the fracture surfaces were examined under a
      stereo microscope. The mean bond strength was 24.37 +/- 3.54 MPa for non
      fluorosed teeth and varied between 22.72 +/- 3.52 and 27.02 +/- 5.91 MPa for
      fluorosed teeth. The difference between the mean values for bond strength was not
      statistically significant (P > 0.05). Adhesive mode of failure was most prevalent
      in non-fluorosed teeth. It can be concluded that fluorosis does not affect the
      shear bond strength of composite material to human dentine.

PMID- 14641675
TI  - Relationship between occlusal curvatures and mandibular deviation in orthodontic
      patients with temporomandibular disorders.
AB  - The aim of this study was to investigate the relationships between occlusal
      curvature (OC) and frontal craniofacial morphology in patients with and without
      temporomandibular disorders (TMD), using frontal cephalograms and a sophisticated
      measuring device (XYZAX S400A). Thirty-seven female orthodontic patients (mean
      age 24.0 years) were divided into a TMD group (n = 25) and no-TMD group (n = 12).
      In the TMD group, the lateral OCs of the mandibular second premolar, and first
      and second molars were significantly deeper on the deviated side than on the non
      deviated side, and the anteroposterior OCs of the mandibular second premolar and
      first molar were also significantly shallower on the deviated side. In the no-TMD
      group, however, there were no significant differences in OCs between deviated and
      non-deviated sides. The differences between right and left lateral OCs in the
      mandibular second premolar and first and second molars, as well as the
      anteroposterior OCs in the mandibular first and second molars, showed significant
      correlations with mandibular deviation in the TMD group. On the other hand, in
      the no-TMD group, there was no significant correlation between OCs and mandibular
      deviation. The above results suggest that OCs might try to compensate for
      mandibular deviation in patients with TMD.

PMID- 14641676
TI  - Influence of number and position of flasks in the monomer release, Knoop hardness
      and porosity of a microwave-cured acrylic resin.
AB  - Simultaneous irradiation of multiple flasks may have deleterious effects on the
      polymerization of microwave cured-acrylic resins. This study evaluated the effect
      of the number and position of flasks in the monomer release, Knoop hardness and
      porosity of a microwave-cured acrylic resin. Samples were made of Acron MC(R)
      (AMC, GC Dent. Ind. Corp.) processed at 500 W. The following associations of the
      number and position of the flasks were tested: one simple flask centrally placed
      on the turning plate (I, control); two flasks, one in the centre (IIa) and the
      other peripherally placed in the plate (IIb); two flasks centrally, one above
      (IIIa) and the other below (IIIb). The processing time varied according to the
      number of flasks: 3 or 4.5 min for one or two flasks, respectively. For monomer
      release, each specimen (n = 12) was put in an assay glass tube containing 6 mL of
      deionized water that was changed daily. Monomer levels were obtained by
      spectrophotometry at 206 nm. For hardness test (n = 10), 12 indentations were
      made in the surface of each specimen. Immersing the polished specimens in
      permanent ink and counting the porous in a stereo light microscope verified the
      porosity. Monomer release was significant before 24 h: GI = 263.1(153.3)a, GIIa =
      236.9(180.2)a, GIIb = 441.5(446.2)a, GIIIa = 1216.6(857.9)b. Tukey test showed no
      statistically significant differences among the groups for porosity and hardness.
      Monomer release was affected by the position of the flask (P < 0.05).

PMID- 14641678
TI  - Report on the determination of occlusal vertical dimension and centric relation
      using swallowing in edentulous patients.
AB  - When constructing a complete denture, the correct vertical dimension of occlusion
      (VDO) and centric relation (CR) can be difficult to determine. The aim of this
      study was to compare the swallowing technique used to determine the
      maxillomandibular relationship with a conventional technique. Fifteen edentulous
      patients were selected, each having a complete denture. The VDO and CR were
      assessed using acrylic base plates and a Boley gauge. First, the VDO was
      established by means of the vertical dimension of rest (VDR) and interocclusal
      rest space, and the CR was obtained by mandibular manipulation. Secondly, the VDO
      and the antero-posterior mandibular position were determined using swallowing.
      All measurements were repeated three times and the average was calculated. The
      results showed that (i). the VDO determined by means of the swallowing method was
      reproducible and significantly higher than the one established from the VDR (P <
      0.01), and (ii). the swallowing position was located 2 mm anterior to CR (P <
      0.01) and was moderately reproducible. This study suggests that swallowing can be
      used to determine the vertical position but no as a reference position in the
      sagittal plane.

PMID- 14641677
TI  - Correlation between maximum bite force and craniofacial morphology of young
      adults in Indonesia.
AB  - The present study was conducted to evaluate the relationship between maximum bite
      force and craniofacial morphology. Sixty-four Indonesian female dental students
      aged 19-27 years with normal occlusion served as the subjects. The Dental
      Prescale System was used to measure the maximum bite force using a pressure
      sensitive sheets while craniofacial morphology measurements were determined from
      conventional lateral radiograms. The antero-posterior and right-left position of
      the occlusal load centre (the OLC) were measured also. Stepwise multiple
      regression analysis was performed to evaluate the relationship between bite force
      and craniofacial morphology while correlation analysis was used to evaluate the
      antero-posterior position of the OLC related to craniofacial morphology. Fifty
      five per cent of the bite force could be explained by variations in the posterior
      facial height, gonial angle, antero-posterior size of the maxilla, and posterior
      length of the cranial base. The result showed a larger bite force implies a
      greater posterior facial height, smaller gonial angle, larger maxilla and
      straighter posterior length of the cranial base. This study suggests that among
      Indonesians, maximum bite force could be explained by craniofacial morphology as
      found in Caucasians. In addition, we proposed a clinical standard of the OLC for
      the comprehensive evaluation of occlusion.

PMID- 14641679
TI  - Effect of non-vital tooth bleaching on microleakage of coronal access
      restorations.
AB  - This study evaluated the effect of non-vital tooth bleaching on microleakage of
      composite resin/bovine tooth interface at different post-bleaching times. A total
      of 320 teeth were cleaned. A pulp chamber access cavity was made at the lingual
      surface of each tooth. The teeth were randomly divided into four groups: SPH -
      sodium perborate + 30% hydrogen peroxide; SPW - sodium perborate + distilled
      water; CP-37% carbamide peroxide; and CON-distilled water (control). The
      bleaching agents were replaced every 7 days, over 4 weeks. Following bleaching
      procedures, the groups were divided into four subgroups (n = 20), according to
      the post-bleaching times: 0 (baseline), 7, 14 and 21 days. After that, the
      cavities were restored with an adhesive system (Single Bond; 3M Co., St Paul, MN,
      USA) and a composite resin (Z100/3M). The specimens were thermocycled, stained
      with 2% methylene blue solution (pH 7), and sectioned longitudinally. The teeth
      were evaluated blind and independently by three previously calibrated examiners,
      to provide representative scores. The data were submitted to Kruskal-Wallis and
      multiple comparison tests (alpha=0.05). At baseline and 7 days, the SPH group
      showed a higher degree of dye penetration than the CON (P=0.04). At 14 and 21
      days, there were no differences among groups. The association of sodium perborate
      with 30% hydrogen peroxide or with water may affect the sealing ability of
      composite resin restorations performed up to 7 days after bleaching procedures.

PMID- 14641680
TI  - Expression of c-Fos protein in the trigeminal nuclear complex resulting from
      quantified force application to the rat molar.
AB  - This study was conducted to investigate the expression and distribution of c-Fos
      like immunoreactive neurones (Fos-neurones), in the rat trigeminal sensory
      nuclear complex, produced by mechanical forces with various magnitudes and
      durations applied to the left upper first molar. The magnitudes of forces applied
      to the tooth were 25, 50 and 100 g and the duration was 2 h. A quantified force
      of 100 g was also applied to the upper molar for varying durations [short-time (1
      2 min)], 2, 4, 8 and 12 h. Fos-neurones distributed in the bilateral superficial
      laminae of the subnucleus caudalis, and the ipsilateral dorsomedial part of
      subnucleus oralis (Sp5Odm). The number of Fos-neurones increased in the
      subnucleus caudalis (Sp5C) according to the force magnitude. In the Sp5C, the
      number of Fos-neurones exhibited maximum level, 2 or 4 h after the application.
      In the Sp5Odm, however, the number of Fos-neurones reached the maximum level at 8
      h. These data suggest that the change in the number of nociceptive neurones in
      Sp5C reflect changes in encoding the magnitude of force to tooth, and that the
      nature of pain response to orthodontic forces might have some relation to the
      delayed expression of c-Fos protein in the Sp5Odm.

PMID- 14641681
TI  - Length of the occlusal glide during chewing in children with primary dentition.
AB  - Chewing is one of the most important functions of the mandible, but, to date,
      there are very few studies of this function in children. The purpose of this
      study was to quantify the length of the occlusal glide at the lower incisal point
      during gum chewing in children with primary dentition. Eleven girls with primary
      dentition were selected for this study. Mandibular excursions with occlusal
      contacts and gum chewing movement were measured using an optoelectronic system
      that can measure mandibular movement with six degrees-of-freedom at a sampling
      frequency of 100 Hz. A curved mesh diagram of incisor coordinates during
      mandibular excursions was established to calculate the length of the occlusal
      glide for each subject. The occlusal glide lengths of children were compared with
      previously reported results for adults. The estimated length of the occlusal
      glide during closing was significantly shorter in children than in adults,
      contrary to that during opening. This result suggests that children have a
      characteristic chewing pattern that differs from adults.

PMID- 14641682
TI  - The effects of HEMA-monomer and air atmosphere treatment of glass fibre on the
      transverse strength of a provisional fixed partial denture resin.
AB  - This study focused on some mechanical properties such as the transverse strength,
      the maximal deflection, and the modulus of elasticity of resin reinforced with
      two different types of agents-treated and with untreated glass fibre, and without
      fibre. A Teflon mould was used to prepare six groups of specimens. Two different
      types of chemical modification agents, hydroxyethyl-methacrylate (HEMA)-monomer
      and air atmosphere were applied to create hydrophilic surfaces on the glass
      fibres. The flow rate was kept at two different levels, 25 and 60 mL min-1. The
      discharge powers of the surface treatment process were 15 or 20 W. The fibres
      were exposed to glow discharge conditions for the periods of 10 or 15 min.
      Without fibre specimens were the control group. The provisional resin was same in
      all groups. All the specimens were subjected to transverse testing with a cross
      head speed of 5 mm min-1. The three-point load test was used to record the load
      of the fracture for each specimens. The Kruskal-Wallis analysis of variance was
      used to compare the transverse strength, the maximal deflection and the modulus
      of elasticity. The differences in the transverse strength and the maximal
      deflection between the six groups were found statistically significant but the
      modulus of elasticity was not statistically significant. The transverse strength
      of HEMA-monomer (group A) was shown the highest value (66.3 MPa). For without
      fibre group, the value was 52.9 MPa. This difference was statistically
      significant when the Mann-Whitney U-test was used for comparing. Repairing or
      remaking provisional restorations can be a time-consuming endeavour. The added
      strength of the polymethyl methacrylate with the fibre can reduce clinical
      failures of provisional fixed partial dentures. The surface treatment process was
      increased the transverse strength and the maximal deflection. The clinical
      implication of chemical modification agents-coated fibres is reduced incidence of
      fixed provisional restoration failure.

PMID- 14641683
TI  - Post-partum endomyometritis diagnosis and treatment: a review.
AB  - Over the past 80 years, obstetrical treatment strategies devised to control
      current problems have resulted in the emergence of new types of infection. These,
      in turn, have caused modifications in diagnostic techniques and treatment
      specifics. Currently, the two most obvious changes influencing post-partum
      infection care are shortened post-partum hospital care, and the widespread use of
      intra-partum antibiotics to prevent early onset Group B streptococcal sepsis in
      the newborn. In the present review, risk factors for post-partum infection are
      delineated and strategies for prophylaxis and treatment are given.

PMID- 14641684
TI  - Sling operations in the treatment of stress urinary incontinence: how to adjust
      sling tension.
AB  - AIM: To find an objective method of adjusting sling tension in order to avoid
      postoperative urinary obstruction. METHODS: Thirty-five female patients with type
      II/III and type III stress urinary incontinence were treated using a sling
      procedure. Pubovaginal fascial slings were implanted in 20 patients and
      polytetrafluoroethylene patch slings with nylon sutures were implanted in 15
      patients. During the procedures the urinary bladder was partially full and the
      patients, who were under spinal or epidural anesthesia, were asked to cough and
      strain. The proper tension that effectively prevents urine leakage was selected
      and the corresponding suture length was marked. An objective new method to adjust
      sling tension was used. As part of this method, the abdominal bulge index is
      added to the suture length before tying. RESULTS: Short-term follow-up of 6-12
      months showed that 33 of 35 patients reported no leakage of urine (94%). Two
      patients had unsatisfactory urge incontinence. We did not encounter postoperative
      urinary retention in any patient. No significant post-voiding residual urine was
      reported. None of our patients in this series have complained of difficulties
      during micturition or the need to strain during voiding. CONCLUSION: Proper
      adjustment of sling tension using the abdominal bulge index has eliminated
      postoperative urinary retention and obstructed urine flow, including any
      appreciable amount of post-voiding residual urine. This method has been found to
      be both objective and reproducible.

PMID- 14641685
TI  - Compliance with hormone replacement therapy at Songklanagarind Hospital.
AB  - AIM: To determine compliance with hormone replacement therapy (HRT) over a 2-year
      period, reasons for discontinuing HRT and the factors associated with non
      compliance. METHODS: A total of 202 women attending the menopause clinic at
      Songklanagarind Hospital and taking HRT were included in this retrospective
      study. Compliance was assessed for each 6-month interval within the first 2
      years. Reasons for discontinuation were requested from women who had stopped
      using HRT. RESULTS: Compliance rates with HRT for the study group were 57.9% at 6
      months, 42.6% at 12 months, 35.1% at 18 months and 32.7% at 24 months. The main
      reasons for discontinuing HRT were improvement of climacteric symptoms (20.9%),
      fear of cancer (16.4%) and irregular bleeding (11.9%). Logistic regression
      analysis revealed a significant increase in the risk of non-compliance of HRT
      among agriculturists or untrained workers (OR 4.7, 95% CI 1.2-18.8; reference,
      government employees), those with delayed onset of treatment (>1 years; OR 3.0,
      95% CI 1.1-8.0; reference, 0-3 months) and those prescribed HRT for climacteric
      symptoms or reasons other than oophorectomy or ovarian failure (OR 18.2-41.6
      depending on reasons). Agriculturists or untrained workers who delayed onset of
      treatment for climacteric symptoms had the highest expected non-compliance rate
      of 0.95%. CONCLUSION: Long-term compliance of HRT was not good at Songklanagarind
      menopause clinic. More attention has to be paid to the counseling of patients
      about HRT. Agricultural or untrained workers, late starting HRT, and presence of
      climacteric complaints were the significant factors for poor HRT compliance.

PMID- 14641686
TI  - Hyalinizing spindle cell tumor with giant rosettes of the omentum.
AB  - We report the first case of a hyalinizing spindle cell tumor with giant rosettes
      of the omentum. The mesenchymal tumor arises from a multiplication of
      fibroblastic cells containing large rosette-like structures composed of a central
      collagen core surrounded by plump oval to spindle tumor cells. A 38-year-old
      woman exhibited the symptom of abdominal pain in the right side, with a
      correlated sensation of a mass in the same area. A tumor consisting of both solid
      and cystic cytologic features was subsequently diagnosed, on the right side of
      the uterus. Her serum level of CA-125 was only slightly elevated. Surgical
      intervention indicated that the tumor originated from lower pole of the omentum
      and the histological diagnosis was hyalinizing spindle cell tumor with giant
      rosettes. The metastatic potential of this type of tumor is considered similar to
      that of the metastatic low-grade fibromyxoid sarcoma, which indicated the need
      for careful clinical follow up of this case.

PMID- 14641687
TI  - Schistosoma mansoni pseudo-cyst as a cause of chronic pelvic pain.
AB  - A case of mansoni schistosomiasis causing peritoneal inflammation and chronic
      iliac pain is reported. The patient complained of iliac pain for 6 months.
      Physical examination and sonographic evaluation found a tumor in the left iliac
      fosse. A pseudocyst was removed from the pelvic region. The histopathology
      confirmed the diagnosis of S. mansoni. This is a rare case of S. mansoni in the
      pelvic cavity.

PMID- 14641688
TI  - Leiomyoma of the vagina: an unusual presentation.
AB  - Vaginal leiomyomas are rare. They usually arise from the anterior vaginal wall.
      We report a case of a vaginal leiomyoma arising from the right lateral wall that
      presented as a gluteal swelling with pus discharging per vagina, creating a
      clinical dilemma in diagnosis. Preoperative imaging and biopsy may help to rule
      out malignancy. The size of the tumor necessitated abdominoperineal approach and
      hysterectomy for better surgical access. To the best of our knowledge such a
      clinical presentation of a vaginal leiomyoma has not been reported in the
      literature.

PMID- 14641689
TI  - Imperforate hymen: report of an unusual familial occurrence.
AB  - Imperforate hymen is an uncommon obstructive anomaly of the female reproductive
      tract, which usually presents with intermittent and cyclical abdominal pain.
      Although it is usually sporadic, four cases of familial occurrence of imperforate
      hymen have been reported so far. Imperforate hymen is seldom associated with
      complications if it is detected early. In view of the possible familial
      occurrence, it is important to have a high index of suspicion in women who
      present with imperforate hymen. A detailed menstrual history of other female
      family members is necessary to enable early detection.

PMID- 14641690
TI  - Facial and body blood contamination in major gynecologic surgeries.
AB  - AIM: To determine the incidence of facial and body blood contamination in various
      major gynecologic surgeries. METHODS: A prospective study was conducted over a 6
      month period on 122 major gynecologic surgeries (abdominal and vaginal) to
      determine the incidence of blood splashes on masks, goggles (or spectacles), body
      and feet of surgeons and assistants. RESULTS: The overall incidence of blood
      splashes was 49.18%, 59.5%, 28.68% and 22.95% on surgeons masks, goggles, body
      and feet, respectively. This incidence was significantly higher (P < 0.05) than
      for first assistants, who showed an incidence of blood splashes of 35.24% (mask),
      38.13% (goggles), 20.49% (body) and 9.83% (feet). The lowest incidence of
      splashes was seen on second assistants, with 22.1% (mask), 24.73% (goggles),
      10.52% (body) and 7.36% (feet). There was no significant difference in the facial
      splash rate between major abdominal and vaginal surgeries, but body and feet
      contamination was significantly higher in major vaginal surgeries (P < 0.05).
      CONCLUSION: There is a very high risk of facial and body blood contamination in
      major gynecologic surgeries, putting the surgeon and assistants at risk of
      acquiring viral disease. Routine use of universal precautions in all gynecologic
      surgeries is strongly recommended.

PMID- 14641691
TI  - Single dose nasal 17beta-estradiol administration reduces sympathovagal balance
      to the heart in postmenopausal women.
AB  - AIM: Long-term estrogen replacement therapy has favorable results on autonomic
      cardiovascular functions in postmenopausal women. Although acute estrogen
      administration has beneficial modulations on autonomic tone in animal studies,
      there are still controversies about the effects of acute estrogen on autonomic
      modulation to the heart in humans. The aim of this double-blind study was to
      investigate the acute effects of intranasal 17beta-estradiol administration on
      autonomic control of heart rate. METHODS: Nineteen postmenopausal women with
      typical hormone profiles were crossover randomized to 300 micro g nasal 17beta
      estradiol (Aerodiol, Servier, Chambray-les-Tours, France) or an identical placebo
      at least 5 days apart. Both time domain and frequency domain heart rate
      variability (HRV) parameters were obtained during controlled respiration (CR) and
      handgrip exercise (HGE), before and 45 min after 17beta-estradiol or placebo
      administration. RESULTS: Baseline HRV parameters were similar for each occasion.
      Time domain indices obtained after 17beta-estradiol administration were not
      significantly different from results obtained with the placebo. In frequency
      domain parameters, 17beta-estradiol administration resulted in a reduced low
      frequency to high frequency ratio (LF/HF ratio) when compared with the placebo
      during CR (0.72 +/- 0.09 vs 1.00 +/- 0.15, P < 0.05) but not during HGE (3.03 +/-
      0.37 vs 2.86 +/- 0.30, P > 0.05). CONCLUSION: A single intranasal 17beta
      estradiol administration acutely reduced sympathovagal balance to the heart
      during the course of parasympathetic maneuver in healthy postmenopausal women.

PMID- 14641692
TI  - Successful management of a pregnant woman with heterozygous protein C deficiency
      using activated protein C concentrate.
AB  - Heterozygous protein C deficiency frequently causes deep vein thrombosis during
      pregnancy. We report the successful management of delivery using activated
      protein C concentrate in a patient with heterozygous protein C deficiency, who
      developed deep vein thrombosis in mid gestation.

PMID- 14641693
TI  - Effect of insulin on rat ovarian leptin expression by immunohistochemical
      staining.
AB  - AIM: Leptin and insulin may interact in regulating ovarian steroid synthesis. The
      objective of this study was to investigate immunohistochemical staining of leptin
      in normal rat ovarian tissues and in rats treated with insulin and insulin plus
      human chorinoic gonadotropin (hCG). METHODS: Paraffin blocks of rat ovarian
      tissues from a previous study, in which 18 adult, female Wistar rats with an
      average weight of 250 g were divided into three groups to receive either saline
      solution, human insulin (2 U/day) or human insulin (2 U/day) plus hCG (4 U/day)
      for 4 weeks, were used in this study to compare the effects on leptin staining.
      The results were analysed using a semiquantitative scoring system, such as mild,
      moderate and strong. RESULTS: No staining was observed in granulosa cells and
      theca interna cells of normal ovarian tissues. Theca externa cells had mild
      staining intensity (+), corpus luteum had moderate (+ +) and stroma had mild (+)
      staining intensity. Histological structure was impaired in the insulin group,
      luteinized cells had mild staining, there was no difference in other cell groups.
      Only theca externa cells of the developing follicles were stained in insulin plus
      hCG group, luteinized cells again had mild staining. CONCLUSIONS: Besides
      damaging the rat ovarian structure, insulin reduced staining intensity of leptin
      in luteinized cells. Insulin may stimulate ovarian steroid synthesis not only
      through its own receptors, but also by acting on the leptin expression of these
      cells.

PMID- 14641694
TI  - Changes in serum concentrations of tumor necrosis factor alpha and adhesion
      molecules in normal pregnant women and those with pregnancy-induced hypertension.
AB  - AIM: To study whether serum tumor necrosis factor alpha gene (TNFalpha) and
      adhesion molecule levels are indicators of the onset of pregnancy-induced
      hypertension (PIH), we compared levels of these molecules between normal pregnant
      women and PIH patients from the first to the third trimester. METHODS: We
      serially measured serum concentrations of TNFalpha, soluble intercellular
      adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), soluble vascular
      cell adhesion molecule-1 (sVCAM-1) and soluble P-selectin (sP-selectin) using
      enzyme immunoassay kits in 10 normal pregnant women and 10 pregnant women who
      developed PIH late in gestation. RESULTS: Serum TNFalpha, sICAM-1 and sE-selectin
      levels in PIH affected women were significantly higher from the first trimester
      compared with those in normal pregnancy. sVCAM-1 and sP-selectin levels were not
      significantly changed. CONCLUSION: Serum TNFalpha, sE-selectin and sICAM-1 levels
      might be effective indicators of the onset of PIH.

PMID- 14641695
TI  - Prenatal diagnosis for placental steroid salfatase deficiency with fluorescence
      in situ hybridization: a case of X-linked ichthyosis.
AB  - X-linked ichthyosis (XLI) is a relatively common genetic disorder that occurs in
      about one in every 2000-6000 male births. Clinically, XLI is characterized by a
      generalized scaling of the skin, with large, polygonal, dark brown scale, and
      more prominent on the extensor aspects of the limbs. It is known that an
      undetectable maternal serum, unconjugated estriol, associated with placental
      steroid sulfatase (STS) deficiency, may be the cause of cause of XLI. In most
      case, STS deficiency is caused by a complete or partial deletion of the STS gene
      mapped on chromosome Xp22.3. We describe here the prenatal detection of a male
      fetus affected with STS deficiency as a result of an undetectable unconjugated
      estriol in the second-trimester maternal serum screening. Microdeletion of the
      STS gene was confirmed by fluorescence in situ hybridization analysis of cultured
      amniotic fluid.

PMID- 14641696
TI  - Anemia in pregnancy.

PMID- 14641698
TI  - Lipid peroxidation and vitamin E status in gestational diabetes mellitus.
AB  - AIM: To investigate any correlation between plasma levels of lipid peroxides,
      antioxidant nutrient (alpha-tocopherol) and oxidized high-density lipoprotein
      (HDL) in patients with gestational diabetes and those with a normal pregnancy and
      the incidence of pre-eclampsia. METHODS: Sixty pregnant women attending an
      antenatal clinic were recruited for the study and were divided into two groups.
      Thirty women with gestational diabetes mellitus were recruited in the study
      group. The glucose-tolerance-test criteria, using 100 g of glucose taken orally,
      as laid down by the American College of Obstetricians and Gynecologists (1994)
      for diagnosis of gestational diabetes mellitus was used. Thirty gestation-matched
      pregnant women with normal glucose tolerance test results were recruited as
      controls. A 10 mL venous blood sample was collected from each subject at the time
      of recruitment and thereafter at 4 week intervals until the time of delivery.
      Samples were analyzed for malondialdehyde thiobarbituric acid reactive, oxidized
      HDL-cholesterol and alpha-tocopherol. The incidence of pre-eclampsia and its
      correlation with antioxidant and lipid peroxide levels were compared in both the
      groups. RESULTS: Ten subjects out of 30 in the study group and three subjects out
      of 30 in the control group developed pre-eclampsia. The incidence of preterm
      labor in both the groups was same (16.66%). The mean lipid peroxide level was
      lower in the study group at recruitment and later the levels kept falling,
      whereas levels of alpha-tocopherol and oxidized-HDL were higher in the study
      group and kept on rising at follow up. CONCLUSION: Gestational diabetes is not
      associated with increased levels of lipid peroxides and decreased levels of alpha
      tocopherol.

PMID- 14641699
TI  - Pheochromocytoma associated with pregnancy.
AB  - Pheochromocytoma associated with pregnancy is rare with potentially lethal
      consequences. Antepartum diagnosis improves the maternal and perinatal outcome.
      The issue of mode of delivery is unresolved. Its definitive treatment is surgical
      resection preceded by medical management. Surgical resection may be done during
      caesarean section as is reported in the present case.

PMID- 14641700
TI  - Ovarian endodermal sinus tumor in a 76-year-old woman.
AB  - A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm
      right ovarian tumor was discovered. On histopathological examination, she was
      diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient
      was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of
      disseminated disease four years later.

PMID- 14641701
TI  - Fetal hemorrhage associated with congenital intestinal atresia.
AB  - We encountered two cases of severe intrauterine hemorrhage associated with
      congenital intestinal atresia. In both cases, the first sign that necessitated
      immediate clinical management was the abnormal fetal heart rate patterns,
      represented by prolonged bradycardias and late decelerations. This occurred
      immediately after the onset of labor. An emergency cesarean section was performed
      on both patients and, despite being born with severe anemia, the condition of the
      infants was excellent. We found that continuous fetal heart rate monitoring
      should be performed if polyhydramniosis suspected, when the fetus is diagnosed
      with congenital intestinal atresia and when changes in intrauterine pressure are
      clinically expected, such as at the onset of labor or after amniocentesis.

PMID- 14641702
TI  - B-Lynch Brace Suturing in primary post-partum hemorrhage during cesarean section.
AB  - Primary atonic post-partum hemorrhage during lower segment cesarean section,
      which was not controlled by ecbolics--oxytocin, methylergometrine, 15-methyl
      prostaglandinF2alpha--was managed by applying a B-Lynch Brace Suture. The test of
      potential efficacy was the control of hemorrhage by bimanual uterine compression.
      Six primigravida patients at their term gestation, who underwent emergency
      cesarean section, all except one under spinal anesthesia, received this type of
      suture. Interestingly, in every case hemorrhage was controlled successfully with
      the compression suture. None of them received blood or blood products
      transfusions or developed disseminated intravascular coagulopathy. Postoperative
      recovery was good and all patients are in follow-up to assess their future
      reproductive activity. B-Lynch Brace Suturing is an invaluable procedure for the
      control of atonic primary post-partum hemorrhage following cesarean delivery.

PMID- 14641703
TI  - The outcomes of assisted reproductive technology cycles in patients with one or
      two ovaries.
AB  - AIM: To provide a comparison between the follicular response to ovulation
      induction, and the pregnancy rate of women with a single or two ovaries,
      undergoing assisted reproductive technology. METHODS: To evaluate the outcome of
      assisted reproductive technology, 46 treatment cycles in women with one ovary
      were compared to 123 cycles in women with two ovaries. RESULTS: The mean age of
      the patients in the two groups were not similar (34.4 +/- 3.8 and 33.1 +/- 4.0,
      respectively). The one ovary-group had significantly higher mean baseline
      Follicle Stimulating Hormone levels and required more ampoules for induction.
      Although the induction period was longer in the one-ovary group, the outcome of
      the assisted reproductive technology in both groups was similar. The maximum E2
      levels on the day of Human Chorionic Gonadotropin administration were
      significantly lower in the one-ovary group, although endometrial thickness
      appeared to be the same in both groups. The patients with two ovaries had a
      significantly higher mean number of mature or immature oocytes aspirated, as well
      as embryos transferred. Although there was no statistical difference between the
      two groups following assisted reproductive technology, the pregnancy rate in the
      two-ovary group was more than double that of the one-ovary group. CONCLUSION: The
      potential for success after in vitro fertilization is not impaired in women with
      one ovary.

PMID- 14641704
TI  - Cotyledonary-like placenta associated with severe intrauterine growth
      restriction.
AB  - There have been no previous reports of human placentas mimicking the cotyledonary
      placenta of ruminants. We report a case of cotyledonary-like placenta associated
      with severe intrauterine growth restriction. A woman pregnant for the first time
      was referred to our hospital at 27 weeks' gestation because of severe
      intrauterine growth restriction. Characteristics of the placenta in the patient
      were examined by ultrasonographical and histopathological techniques.
      Ultrasonography revealed that a hypo-echoic area intermingled with small
      segmented tissues in the placenta. The hypo-echoic area changed in size and shape
      according to uterine contractions. At 31 weeks' gestation, a caesarean section
      was performed because of non-reassuring fetal status. A female baby weighing 814
      g was delivered. The placenta, which weighed 260 g, contained several long stem
      villi running over a distance of 6 to 7 cm without branching into intermediate or
      terminal villi. Small villous tissues had developed only at the tips of these
      stem villi. The present case shows an extraordinarily abnormal development of the
      villous trees in the placenta, which may have caused fetal IUGR and non
      reassuring fetal status.

PMID- 14641705
TI  - Complete hydatidiform mole in a triplet pregnancy coexisting two viable fetuses:
      case report and review of the literature.
AB  - We report a rare case of a complete hydatidiform mole with two or more coexisting
      fetuses where both infants survived without complications. A male infant weighing
      1258 g and a female infant weighing 880 g were delivered without complications
      and discharged 95 days after the birth. The analysis of DNA microsatellite
      polymorphisms indicated that the mole was of paternal origin and probably
      homozygous. The mother suffered from multiple pulmonary metastasis of the
      hydatidiform mole which was detected 3 days after the surgery and was
      successfully treated with methotrexate. A complete hydatidiform mole with two or
      more coexisting fetuses produces a dilemma between immediate termination and
      pregnancy continuation. Although the present case resulted in a favorable
      outcome, a review of the 14 reported cases suggests that the high fetal loss rate
      (90%) must be a consideration in the decision regarding management of such a
      pregnancy.

PMID- 14641706
TI  - Cardiac failure caused by severe pre-eclampsia with placental abruption, and its
      treatment with anti-hypertensive drugs.
AB  - Pre-eclampsia is the abnormality of blood circulation in late pregnancy, often
      caused by renal failure, hemolysis, elevated liver enzyme, low platelet syndrome,
      and eclampsia. We present a case of severe pre-eclampsia with placental abruption
      in a 24-year-old woman, pregnant for the first time. The patient was diagnosed
      with congestive heart failure, which came as a result of pre-eclampsia. Anti
      hypertensive drugs were used for its treatment.

PMID- 14641707
TI  - In utero diagnosis of an aneurysm of the vein of Galen causing hydrocephalus and
      heart failure.
AB  - A prenatally diagnosed aneurysm of the vein of Galen was presented in the fetus
      of a patient referred to our hospital at 31 weeks of gestation. Ultrasonography
      demonstrated polyhydramnios, cardiomegaly, dilatation of the right atrium and
      superior vena cava, tricuspid valve regurgitation, hydrocephalus, and a large
      hypoechoic mass with blood flow in the suboccipital region. Skin edema was shown
      thereafter. A 3262-g male was delivered by cesarean at 35 weeks of gestation.
      Computed tomography imaging demonstrated a large mass in the suboccipital region,
      after which thrombocytopenia appeared and the neonate died at 18 days of age.

PMID- 14641708
TI  - Fetal hepatic hemangioma representing non-reassuring pattern in fetal heart rate
      monitoring.
AB  - To the best of our knowledge, this is the first report of a non-reassuring fetal
      pattern caused by a hepatic hemangioma that was found during fetal heart rate
      monitoring. A 37 weeks' gestation, a 32-year-old-woman was referred to our
      hospital for evaluation of a rapidly growing fetal abdominal tumor. Fetal heart
      rate monitoring revealed a non-reassuring pattern, and a cesarean section was
      performed as a result. Examination of the 2820 g female infant suggested a
      hepatic hemangioma accompanying an intratumor hemorrhage and coagulopathy. The
      infant died 2 days after birth. The autopsy confirmed that the cause of death was
      a result of a hepatic hemangioma. Frequent monitoring of fetuses and ultrasound
      examinations are necessary for determining the timing of delivery and for a
      favorable prognosis.

PMID- 14641710
TI  - JSOG Best Paper Award 2002: 1.

PMID- 14641709
TI  - Preventable but not prevented: the reality of cervical cancer.
AB  - INTRODUCTION: The incidence of invasive cervical cancer has decreased in the last
      50 years in the developed countries substantially due to the use of routine pap
      smears. However, in the Asia-Oceanic region it continues to be high as screening
      programs are not established. Credit for starting cytology services in India goes
      to Professor P.N. Wahi of Agra. He became Founder President when about 34
      cytologists got together in 1970 to form the Indian Academy of Cytologists. Since
      then cytology has spread through all parts of India. The Cytology Clinic in Cama
      & Albless Hospital was started in the same year. Since then over 100000 women
      have been screened. Approximately 1200 cases of pre- and early cancers have been
      detected and treated. Since 1982 we are aware of the important role of human
      papillomavirus infection. We diagnose it by cytology and colposcopy and
      histology. Facilities for polymerase chain reaction, in-situ hybridization and
      other virology studies are not available to us. CO2 laser treatment is found
      particularly useful in multicentric human papillomavirus disease. SCREENING FOR
      THE STATE OF MAHARASHTRA: Since 1984 we have planned for a screening program for
      our State. We have a population of 78.9 million. Approximately 15 million women
      in the age group of 35-64 years have to be screened. The health care
      infrastructure is good with 36 medical colleges and over 35 district hospitals.
      Screening is planned in phases. Trained personnel are the key to a successful
      program. In the final analysis, cervical cancer is not just a biomedical disease.
      It has socio-cultural and economic implications.

PMID- 14641711
TI  - Relationship between Fertilizing Ability of Ejaculated Human Spermatozoa and Its
      Chromatin Heterogeneity.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between the
      fertilizing ability of ejaculated human sperm and its chromatin heterogeneity.
      METHOD: We used the D-AO staining method (acridine orange epifluorescence
      accompanied by diamide, a thiol oxidizing agent) to analyze the sperm chromatin
      structure of infertile patients with IVF-ET treatment. SDS-PAGE was performed to
      analyze the sperm nuclear proteins collected from patients with immature sperm
      (stained red with D-AO staining) and proven fertile men. RESULTS: 1. It was
      suggested that D-AO staining allowed the immature sperm to be divided into two
      groups. One was immature sperm, which had disturbance of S-S formation in the
      epididymides, and the other was sperm that which had an abnormal exchange process
      of nuclear proteins in the testes. 2. The stainability after D-AO staining showed
      no correlation with the findings of semen analysis. 3. The fertilization rate of
      IVF-ET was significantly correlated to the percentage of green sperm staining
      with D-AO staining. 4. In the pregnant group after IVF-ET, it was noticed that
      sperm of the green type with D-AO staining was increased in comparison with the
      non-pregnancy group. 5. The fertilization rate in the group of the sperm stained
      red with D-AO staining was increased to 73.5% by ICSI. 6. Definite differences
      were noticed between the protein components of the patients with immature sperm
      and those of the proven fertile men by analysing with SDS-PAGE. CONCLUSION: D-AO
      staining was an efficient method for evaluating the fertilizing ability of human
      ejaculated sperm, and to determine an appropriate ART tool such as ICSI.

PMID- 14641713
TI  - JSOG Best Paper Award 2002: 4.

PMID- 14641712
TI  - Study on the Mechanism of the Bone Formation Process by 17beta-estradiol during
      Rat Bone Marrow Stromal Cell Culture.
AB  - The aim of this study is to clarify the mechanism of bone formation by using
      17beta-estradiol (E2) during rat bone marrow stromal cell culture. Stromal cells
      were separated from female rat femora (seven weeks old), and were cultured in an
      Eagle Minimal Essential Medium (MEM) containing 15% fetal calf serum (FCS). After
      confluence, the cells were subcultured in a MEM containing 15% FCS (sex steroids
      removed by charcoal treatment) with dexamethasone, Na betaglycerophosphate and
      ascorbic acid phosphate for 18 days. They were then cultured in medium containing
      E2 or insulin-like growth factor-Iota (IGF-Iota) alone or with anti-IGF-Iota
      antibody. On the 14th day, the formation of white colored nodules showing
      positive ALP activity in ALP staining and showing calcium deposition in alizarin
      red S staining was observed in each culture system, indicating the beginning of
      calcification. The addition of E2 (10-7M or 10-8M), or IGF-Iota (10 and 100
      ng/ml) enhanced ALP activity and calcium content significantly, but 17alpha
      estradiol did not. Anti-IGF-Iota antibody significantly inhibited enhancing
      effects of E2 and IGF-Iota on ALP activity and calcium deposition. Incubating
      with E2 alone (10-8M), the medium IGF-Iota concentration and IGF-I mRNA
      expression in the cells were significantly increased on days 10~14, but the
      expression of IGF-Iota receptor mRNA had not changed. These results suggest that
      E2 participates in bone formation by promoting IGF-Iota production in the bone
      marrow stromal cells just before calcification starts.

PMID- 14641714
TI  - Congresses/Meetings of Obstetrics and Gynecology.

PMID- 14641717
TI  - Interdisciplinary team leadership: a revisionist approach for an old problem?
AB  - Understanding of interdisciplinary teamwork is evolving. During health care
      restructuring, leaders across organizations have challenging responsibilities
      when work groups must integrate changing organizational values with new modes of
      service delivery. In this environment, a well-functioning interdisciplinary team
      in which clinicians work as member-leaders has the potential to further
      organizational change and foster improvements in patient outcomes. In this paper
      it is argued that the term interdisciplinary team leadership should be embraced
      cautiously as it may be a revisionist approach to an old problem, namely a means
      to modify existing theories of leadership that have been vague and continue to be
      poorly understood despite considerable effort to explicate knowledge over several
      decades. Preliminary research suggests that interdisciplinary team leadership is
      a model of shared leadership that requires more development if it is to become
      the cornerstone of interdisciplinary team practice in a radically reforming
      health sector. Stewardship is proposed as a potential philosophy for
      interdisciplinary team leadership, and a new, shared leadership role of practice
      leader is suggested.

PMID- 14641718
TI  - The importance of leadership in the development of an integrated team.
AB  - AIM: To provide a personal perspective on the role of leadership within the
      development of an integrated team. BACKGROUND: The government white paper Valuing
      People recently proposed that collaborative working is essential in service
      delivery for people with a learning disability. This has led to the development
      of the integrated team to respond the often complex needs of people with a
      learning disability. METHOD: A situational analysis is used to outline the
      history, and the changes within learning disability services. The role of self,
      team development and leadership are then explored in achieving future change and
      objectives. CONCLUSION: Transformational skills are essential in the development
      of team working, however, understanding and commitment to the process of
      collaboration is required by all agencies and at all levels in order to implement
      change. Nurses are placed in influential positions within the change process.

PMID- 14641719
TI  - Health Visitors' experiences of Family Group Conferences in relation to child
      protection planning: a phenomenological study.
AB  - AIMS AND BACKGROUND: The purpose of this study was to explore Health Visitors'
      experiences of Family Group Conferences as part of Child Protection Planning in
      Hampshire, England. The aim was to identify good practice, recognizing the
      challenges of the approach and enabling recommendations for improved
      collaboration to be framed. The Family Group Conferences model is based on
      partnership, decision-making and family involvement and presents an alternative
      to case conferences. METHODS: A Husserlian phenomenological approach was adopted,
      using taped semi-structured interviews with four health visitors who had
      experience of Family Group Conferences. Colaizzi's seven stages of
      phenomenological analysis were used. FINDINGS: The four key categories related to
      the ability of the Family Group Conference model to empower families; the need
      for health visitors to receive appropriate education and training;
      organizational; and professional issues. Health visitors believed that Family
      Group Conferences could empower families, but they felt unprepared to attend.
      Concerns were identified regarding confidentiality and responsibility. Although
      the health visitors supported the principles underpinning Family Group
      Conferences, they were unsure about how to put theory into practice. The need for
      more education and training was strongly supported to enable the model to move
      from marginal to mainstream use. They also considered that Family Group
      Conferences could threaten interagency working, associated with issues relating
      to professional responsibility. CONCLUSIONS: The results identified training and
      procedural issues that need to be addressed if Family Group Conferences are to be
      introduced successfully within mainstream child protection practice. Insights
      from this study have led to inclusion of Family Group Conferences in the local
      child protection guidelines, with emphasis applied to interdisciplinary working,
      empowerment of families and professional staff, and education and training.

PMID- 14641720
TI  - Leading interprofessional practice: a conceptual framework to support
      practitioners in the field of learning disability.
AB  - One of the key challenges for practitioners in present day health and social care
      has been responding effectively in the interprofessional teamwork setting, where
      collaboration is at the centre of professional activity. For whilst practitioners
      are expected to work interprofessionally there often remains limited attention to
      the actual process of interprofessional practice itself, within organizational
      strategy, local workforce development planning and individual continuing
      professional development. These concerns were a driver for this research with
      practitioners in the field of learning disability which resulted in the
      development of a conceptual framework for interprofessional practice. This paper
      sets out the process of conceptual framework development, underpinned by the
      concepts of knowledge of learning disabilities, contextual socialisation,
      empowerment, conflict management, transforming capability and interprofessional
      reflection on action. The researcher suggests that the framework may offer
      clinical leaders in learning disabilities and a range of other practice settings
      a tool to facilitate individual practitioner development, enabling as it does,
      the identification of a range of critical factors which impact on the outcomes of
      interprofessional practice intervention.

PMID- 14641721
TI  - Challenges and leadership strategies for managers of nurse practitioners.
AB  - AIM: The aim of this paper is to report on the findings from our research into
      the recent introduction of nurse practitioners in Alberta, Canada. Through an
      organizational research perspective, we identify the critical role of health care
      managers in developing a sustainable nurse practitioner role. BACKGROUND:
      Previous literature has focused on nurse practitioners themselves as the key
      factor in their integration into the health care system. Although they are
      qualified and organizationally well placed, managers of nurse practitioners have
      been overlooked as a critical part of implementation strategies. KEY ISSUES: We
      interviewed 25 nurse practitioners and seven of their managers. Through our data
      analysis we identified three major challenges for managers: (1) clarifying the
      reallocation of tasks; (2) managing altered working relationships within the
      team; (3) continuing to manage the team in an evolving situation. Associated with
      these challenges, we propose leadership strategies that managers may find useful
      as they work through the consequences of introducing the nurse practitioner role.
      These strategies are: * encourage all team members to sort out 'who does what'; *
      ensure that task reallocation preserves job motivating properties; * give
      consideration to how tasks have been allocated when issues identified as
      'personal conflict' arise; * pay attention to all perspectives of the working
      relationships within the team; * facilitate positive relationships between team
      members; * lead from a 'balcony' perspective; * work with the team to develop
      goals that are not over focused on the nurse practitioner; * regularly share with
      other managers the experiences and lessons learned in introducing nurse
      practitioners. CONCLUSION: For managers to be most effective, they need to
      address three challenges that are of a managerial, not clinical, nature. By
      implementing specific leadership strategies, managers of nurse practitioners can
      facilitate the introduction of the new role and improve its sustainability in
      health organizations.

PMID- 14641722
TI  - Comparison of competence assessments made by nurse managers and practising
      nurses.
AB  - This study compares nurse and manager assessments of nurse competence in a
      university hospital setting. Although managers carry out annual reviews, few
      studies have examined the agreement between the competence assessments made by
      practising nurses and their managers. Using a pretested 73-item questionnaire,
      consisting of seven competence categories, we compared self-assessments and
      manager assessments of the level of nurse competence on a Visual Analogue Scale
      of 0-100 and the frequency of using competencies by using statistical analyses.
      Managers assessed the overall level of competence (70.8 +/- 19.3 vs. 63.9 +/-
      13.7) (mean +/- SD) and the level of competence in five competence categories
      significantly higher than the nurses themselves. A high degree of agreement was
      found between the assessments for the frequency of using competencies. These
      results can be used to encourage nurses and to improve the quality of care in
      different hospital work environments.

PMID- 14641726
TI  - Abstracts of the Meeting of the International Society for Neurochemistry, August
      2003.

PMID- 14641723
TI  - The role of the support worker in nursing homes: a consideration of key issues.
AB  - The aim of this paper is to critically consider the role of the support worker in
      the nursing home sector and with particular reference to the United Kingdom
      situation. With the expansion of the nursing home sector, there is an increasing
      population of support workers in this field. Literature in this paper covers the
      period between 1989 and 2002, beginning with the build up to the introduction of
      the National Health Service and Community Care Act (available at:
      http://www.hmso.gov.uk), which necessitated a major shift between public and
      private sector employment. The findings of this paper indicate limited research,
      investigating the role of support workers in general and specifically those
      working in the nursing home sector. The literature suggests that the majority of
      the role focuses on direct patient care, however, a lack of role clarification
      was evident and differences emerged between the views of support workers and
      Registered Nurses regarding the place of support workers in the care process. In
      particular, support workers saw their role as similar to that of the Registered
      Nurse, although Registered Nurse regarded 'basic nursing care' as the key remit
      of the support worker role. The paper also indicated inadequate preparation and
      subsequent supervision of support workers. These key findings indicate that role
      clarification, appropriate preparation and a process of continuing development
      require careful consideration by managers if the positive contribution of this
      group of care workers is to be fully realized. Furthermore, while there exists no
      central source of funding to finance the role preparation and mentorship of
      support workers, training provision will remain ad hoc. Obtaining core funding
      would allow for the training and education of support workers to become standard
      practice, which, in turn, is more likely to lead to improvements in the planning
      and resourcing of care provision. Equally, further research is needed if the
      support worker role is to be used effectively and efficiently within the
      expanding nursing home sector.

PMID- 14641785
TI  - Occurrence of hepatitis viruses in wild-born non-human primates: a 3 year (1998
      2001) epidemiological survey in Gabon.
AB  - Hepatitis B and C infections are endemic in human population in central Africa,
      particularly in Gabon. The aim of this study was to determine the prevalence of
      hepatitis B virus (HBV) and eventual occurrence of hepatitis C virus (HBC)
      related strains in a variety of wild-born non-human primates living in Gabon and
      Congo. Plasma samples were screened for HBV and HCV markers. A non-invasive
      method of DNA extraction from faeces followed by specific HBV-DNA amplification
      was developed to study this infection in wild troops of chimpanzees and gorillas.
      No HCV infection in non-human primates, wild-born or captive, was detected among
      596 samples tested. No HBV infection could be detected in samples tested and
      obtained from Cercopithecidae. In contrast, 14.7 and 42.2% of wild-born
      chimpanzees in Gabon and Congo were infected with HBV or had evidence of past HBV
      infection. At Centre International de Recherches Medicales (CIRMF) Primate
      Centre, 32.1% of chimpanzees and gorillas were HBV positive or had evidence of
      past infection. In the cases with past infection, 5.9% wild-born and 8.3% at
      CIRMF harboured HBV-DNA despite the presence of neutralizing HbsAb. Together with
      previous findings, we confirm the high HBV prevalence not only in humans but also
      in chimpanzees and gorillas in Gabon and Congo.

PMID- 14641786
TI  - Leptin, body composition, adrenal and gonadal hormones among captive male
      baboons.
AB  - Morphometric and hormonal measures were collected from 21 captive savanna baboons
      (Papio cynocephalus) maintained at the Tulane National Primate Research Center in
      order to determine age-related patterns in leptin levels over the life course as
      well as their relationships to body composition and adrenal and gonadal steroids.
      Comparison of leptin levels between peri-pubertal, adolescent, young adult, and
      fully mature males show lower levels among adolescent as compared with young
      adult males (P = 0.05 by Kruskal-Wallis ANOVA). In addition, abdominal fat varied
      among age groups (P = 0.003 by Kruskal-Wallis ANOVA) with the peri-pubertal
      animals lower than the adolescents, young adults, and prime adults. However
      leptin was not related to any measure of body composition, including abdominal
      fat, or to adrenal hormones (dehydroepiandrosterone, dehydroepiandrosterone
      sulfate, and cortisol) or gonadal hormones (testosterone and estradiol). Age
      related changes in leptin appear similar to those reported for captive rhesus
      macaques, while the failure to find an association between leptin and abdominal
      fat is interestingly different. These results confirm elevated levels of leptin
      in captive baboons compared with their wild counterparts and suggest that they
      result from changes in fetal development.

PMID- 14641787
TI  - Characterization of semen from olive baboons.
AB  - Electroejaculation is an accepted method of semen collection from non-human
      primates and is typically performed using direct penile or rectal probe electro
      stimulation. Six mature male olive baboons (Papio anubis) were subjected to
      rectal probe electro-stimulation procedure that yielded 65 usable ejaculates in
      69 attempts over a period of 16 weeks. The four non-usable ejaculates consisted
      of seminal fluid without sperm cells and thus were not analysed. The analysis of
      ejaculate volume, concentration, % motility, liquefaction times, and morphology
      in this study has provided information on the quality of semen samples. It is
      anticipated that this analysis will provide valuable information for male
      fertility studies and the development of an in vitro fertilization (IVF) system
      in the olive baboon as a model for human IVF.

PMID- 14641788
TI  - Genetic analysis of the Saimiri breeding colony of the Pasteur Institute (French
      Guiana): development of a molecular typing method using a combination of nuclear
      and mitochondrial DNA markers.
AB  - Saimiri (Cebidae) groups a complex of species and subspecies, which present a
      large morphological plasticity. Genetic analysis is complicated by the absence of
      consensus on classification criteria and the paucity of molecular tools available
      for the genus. As the squirrel monkey is widely used in biomedical research,
      breeding centers have been established, but the genetic make up and diversity of
      many of the existing colonies is unknown precluding a rationale breeding policy.
      To develop a genetic typing strategy for the Saimiri breeding colony of Pasteur
      Institute of French Guiana, we have used Cytochrome b, a mitochondrial marker,
      and nuclear microsatellites. Cytochrome b sequences from wild-caught Saimiri
      boliviensis, Saimiri sciureus sciureus and S. s. collinsi reference specimens and
      captive animals identified 11 haplotypes, grouped into three distinct clades. An
      estimate of genetic variability within each captive morphotype, and of the extent
      of molecular divergence between the Bolivian, Guyanese and Brazilian breeds was
      obtained from the analysis of three nuclear microsatellites. Taxon-specific
      microsatellites enabled typing of F0-F3 animals, but did not differentiate
      Brazilian from Guyanese animals. Three locus microsatellite analysis of a
      representative sample from each generation showed no trend for loss of
      heterozygosity, and identified hybrid animals between Bolivian and the two others
      sub-species. These data provide novel evidence for taxonomic classification and a
      rationale strategy to further type the whole colony.

PMID- 14641789
TI  - A survey for helminth parasites in feral New World non-human primate populations
      and its comparison with parasitological data from man in the region.
AB  - A survey for helminth parasites in feral New World non-human primates was
      conducted and compared with parasitological data from man in the region. A total
      of 835 fecal samples were collected from feral Aotus nancymae, A. vociferans,
      Saguinus labiatus, S. mystax, Saimiri boliviensis peruviensis, S. sciureus
      macrodon, Lagothrix lagotricha and Cacajao calvus rubicundus. In addition, adult
      parasites were collected from necropsies performed on monkeys that died during
      quarantine and in captivity. Helminth parasites shared by non-human primates and
      man in Peru were Ancylostoma braziliensis and Ascaris lumbricoides, found in a
      captive L. lagotricha; Necator americanus, found in a captive C. calvus
      rubicundus; Hymenolepis diminuta, found in feral Aotus spp. and S. mystax; and a
      single Trichuris spp. specimen found in a feral S. sciureus macrodon.

PMID- 14641790
TI  - Use of a telemetry system to examine recovery of the cardiovascular system after
      excitement induced by handling stress in a conscious cynomolgus monkey (Macaca
      fascicularis).
AB  - The aim of this study was to determine the time required for the cardiovascular
      system of a conscious cynomolgus monkey, in which a telemetry had been implanted,
      to recover from excitement induced by handling stress. With enforcement of
      guidelines regarding safety pharmacological studies, cardiovascular studies in
      primates have become more important. However, as macaque monkeys are promptly
      excited under experimental procedures, it is often difficult to evaluate the drug
      effects on the cardiovascular system. Therefore, we tested monkey chair restraint
      and intravenous injection of saline. After monkey chair restraint and intravenous
      injection, approximately 30 minutes were required for recovery of both heart rate
      and blood pressure to their pre-treatment level; however, ECG parameters such as
      PR, QRS interval, and QTc did not drastically change. Based on our current
      results and with sufficient consideration of autonomic nervous effects, accurate
      evaluation of drug effects on the cardiovascular system should now be possible.

PMID- 14641792
TI  - Imbalance of plasma membrane ion leak and pump relationship as a new aetiological
      basis of certain disease states.
AB  - The basis for life is the ability of the cell to maintain ion gradients across
      biological membranes. Such gradients are created by specific membrane-bound ion
      pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules
      passive forces equilibrate (dissipate) ion gradients. The
      cholesterol/phospholipid ratio of the membrane and the degree of saturation of
      phospholipid fatty acids are important factors for membrane molecular order and
      herewith a determinant of the degree of non-specific membrane leakiness. Other
      operative principles, i.e. specific ion channels can be opened and closed
      according to mechanisms that are specific to the cell. Certain compounds called
      ionophores can be integrated in the plasma membrane and permit specific inorganic
      ions to pass. Irrespective of which mechanism ions leak across the plasma
      membrane the homeostasis may be kept by increasing ion pumping (ATPase activity)
      in an attempt to restore the physiological ion gradient. The energy source for
      this work seems to be glycolytically derived ATP formation. Thus an increase in
      ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This
      can be measured as an accumulation of breakdown products of ATP and end-products
      of anaerobic glycolysis (lactate). In certain disease entities, the balance
      between ATP formation and ion pumping may be disordered resulting in a decrease
      in inter alia (i.a.) cellular energy charge, and an increase in lactate formation
      and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an
      excessive leakage of potassium ions, leading to electrocardiographic (ECG)
      changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by
      adenosine). Cocksackie B3 infections, a common agent in myocarditis might also
      induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized
      by the formation of extracellular amyloid deposits in the brain of patients.
      Perturbation of cellular membranes by the amyloid peptide during the development
      of Alzheimer's disease is one of several mechanisms proposed to account for the
      toxicity of this peptide on neuronal membranes. We have studied the effects of
      the peptide and fragments thereof on 45Ca2+-uptake in human erythrocytes and the
      energetic consequences. Treatment of erythrocytes with the beta 1-40 peptide,
      results in qualitatively similar nucleotide pattern and decrease of energy charge
      as the treatment with Ca2+-ionophore A23187. Finally, in recent studies we have
      revealed and published in this journal that a rare condition, Tarui's disease or
      glycogenosis type VII, primarily associated with a defect M-subunit of
      phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+
      into erythrocytes.

PMID- 14641793
TI  - Do anticoagulants improve survival in patients presenting with venous
      thromboembolism?
AB  - Anticoagulants have been available since around 1940 and have become the standard
      of treatment for venous thromboembolism (VTE) for over four decades. However, as
      with other treatments which became established before the evidence-based era,
      there is a paucity of evidence from randomized controlled trials validating their
      effectiveness in preventing the most feared complication of VTE, recurrent fatal
      pulmonary embolism (PE). Only two such trials have been performed, the results of
      which conflict. The bulk of data supporting their use are derived from three
      sources. First, studies of thromboprophylaxis, and comparisons of shorter and
      longer courses of anticoagulants in high-risk patients with established VTE have
      clearly demonstrated their effectiveness in primary and late secondary
      prevention. Given that heparin has an immediate onset of action, anticoagulants
      should therefore also be effective in early secondary prevention, the proposed
      mechanism of action in the acute treatment of VTE. Secondly, studies of
      inadequately treated patients have consistently shown higher recurrence rates
      than in those adequately treated. Finally, comparisons of outcomes in untreated
      and treated historical series, and of untreated historical series to treated
      series in the modern era have shown substantially lower rates of fatal PE in
      anticoagulated patients. Because these differences are so marked, harmonize with
      our current understanding of the mechanism of action of anticoagulants and are
      supported by other evidence, it is much more likely that they at least partly
      reflect the effectiveness of anticoagulants as opposed to being explicable purely
      in terms of accumulated biases and a changing distribution of disease severity.

PMID- 14641794
TI  - Obstructive and restrictive lung disease and functional limitation: data from the
      Third National Health and Nutrition Examination.
AB  - OBJECTIVE: To determine functional limitations in adults with obstructive or
      restrictive lung disease or respiratory symptoms. DESIGN: Cross-sectional study.
      SUBJECTS: Adult participants in phase 2 of the Third National Health and
      Nutrition Examination Survey, 1991-94. METHODS: We classified subjects using
      spirometric criteria into the following mutually exclusive categories using the
      forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC), the
      FEV1/FVC ratio and the presence of respiratory symptoms: severe obstruction,
      moderate obstruction, mild obstruction, respiratory symptoms only, restrictive
      lung disease and no lung disease. We developed regression models to predict
      functional limitations (unable to walk a quarter of a mile, unable to lift 10
      pounds, needs help with daily activities) that controlled for age, race, sex,
      education, smoking status, body mass index and comorbid conditions. RESULTS:
      Severe and moderate obstruction were associated with an increased risk of being
      unable to walk a quarter of a mile [odds ratio (OR) 8.4, 95% confidence interval
      (CI) 3.6, 19.9 and OR 2.4, 95% CI 1.4, 4.0]. Restrictive lung disease and the
      presence of respiratory symptoms in the absence of lung function impairment were
      also associated with an increased risk of this outcome (OR 2.8, 95% CI 1.4, 5.6
      and OR 2.8, 95% CI 2.0, 3.9). Similar results were obtained for the outcomes of
      being unable to lift 10 pounds or needing help with daily activities.
      CONCLUSIONS: The presence of obstructive or restrictive lung disease, or
      respiratory symptoms in the absence of lung function impairment is associated
      with increased functional impairment.

PMID- 14641795
TI  - Use of alpha-blockers and the risk of hip/femur fractures.
AB  - OBJECTIVE: To study the association between use of alpha-blockers and risk of
      hip/femur fractures. DESIGN: Population-based case-control study. SETTING:
      General Practice Research Database. SUBJECTS: Cases were defined as men, aged 40
      years and older with a first diagnosis for hip/femur fracture. Controls were
      matched 1 : 1 on gender, year of birth and general practitioner-practice.
      RESULTS: In all, 4571 cases and an equal number of controls were identified.
      Current use of alpha-blockers (prazosin, doxazosin, indoramin, terazosin,
      alfuzosin and tamsulosin) was compared with non-use of alpha-blockers. Current
      use of alpha-blockers on the index date was associated with an increased risk of
      hip/femur fracture [adjusted odds ratio (OR) 1.9, 95% confidence interval (CI):
      1.1-3.0] in the overall analysis. The effect was particularly strong for first
      prescriptions within a treatment episode (adjusted OR 5.1, 95% CI: 1.0-31.7) and
      during the first month of treatment (adjusted OR 4.1, 95% CI: 0.7-23.9).
      Stratification according to indication of use showed that current use of alpha
      blockers was not associated with hip/femur fracture in men with a diagnosis of
      benign prostatic hyperplasia (adjusted OR 1.0, 95% CI: 0.4-2.5), but was
      associated in men who used alpha-blockers for cardiovascular disease (adjusted OR
      2.8, 95% CI: 1.4-5.4). CONCLUSION: Current use of alpha-blockers was associated
      with an increased risk of hip/femur fracture and with the start of a new
      treatment episode. The effect seemed to be confined to patients who used alpha
      blockers for cardiovascular disease. Caution with respect to first-dose effects
      related to the initiation of a new episode of alpha-blocker treatment is advised.

PMID- 14641796
TI  - Waist circumference, waist-hip ratio and body mass index and their correlation
      with cardiovascular disease risk factors in Australian adults.
AB  - OBJECTIVES: To compare body mass index (BMI), waist circumference and waist-hip
      ratio (WHR) as indices of obesity and assess the respective associations with
      type 2 diabetes, hypertension and dyslipidaemia. DESIGN AND SETTING: A national
      sample of 11 247 Australians aged > or =25 years was examined in 2000 in a cross
      sectional survey. MAIN OUTCOME MEASURES: The examination included a fasting blood
      sample, standard 2-h 75-g oral glucose tolerance test, blood pressure
      measurements and questionnaires to assess treatment for dyslipidaemia and
      hypertension. BMI, waist circumference and WHR were measured to assess overweight
      and obesity. RESULTS: The prevalence of obesity amongst Australian adults defined
      by BMI, waist circumference and WHR was 20.8, 30.5 and 15.8% respectively. The
      unadjusted odds ratio for the fourth vs. first quartile of each obesity
      measurement showed that WHR had the strongest relationship with type 2 diabetes,
      dyslipidaemia (women only) and hypertension. Following adjustment for age,
      however, there was little difference between the three measures of obesity, with
      the possible exceptions of hypertension in women, where BMI had a stronger
      association, and dyslipidaemia in women and type 2 diabetes in men, where WHR was
      marginally superior. CONCLUSIONS: Waist circumference, BMI and WHR identified
      different proportions of the population, as measured by both prevalence of
      obesity and cardiovascular disease (CVD) risk factors. Whilst WHR had the
      strongest correlations with CVD risk factors before adjustment for age, the three
      obesity measures performed similarly after adjustment for age. Given the
      difficulty of using age-adjusted associations in the clinical setting, these
      results suggest that given appropriate cut-off points, WHR is the most useful
      measure of obesity to use to identify individuals with CVD risk factors.

PMID- 14641797
TI  - Expression of Th1 markers by lung accumulated T cells in pulmonary sarcoidosis.
AB  - OBJECTIVES: The balance between Th1 and Th2 T cells, classified by virtue of
      their cytokine production can in an immune response influence the phenotype and
      progression of several clinical diseases. In this study, we examined the
      expression of Th1 associated chemokine and cytokine receptors CXCR3, CCR5, and
      interleukin (IL)-12R, IL-18R, respectively, as well as of the Th2 associated
      chemokine receptors CCR4 and CXCR4 on CD4+ and CD8+ T cells. SUBJECTS: Eighteen
      patients with untreated pulmonary sarcoidosis. MATERIALS AND METHODS: We used
      monoclonal antibodies and flow cytometry to analyse the expression of chemokine
      receptors CXCR3, CXCR4, CCR4 CCR5 and cytokine receptors IL-12R, IL-18R in
      combination with anti-CD4 and anti-CD8 mAbs in bronchoalveolar lavage fluid (BAL)
      and peripheral blood lymphocytes (PBL) from sarcoidosis patients. RESULTS: There
      were significantly more BAL CD4+ T cells expressing CXCR3, CCR5, IL-12R and IL
      18R compared with paired PBL CD4+ T cells. In contrast, the Th2 associated
      chemokine receptors CXCR4 and CCR4 were expressed by a fewer percentage of BAL
      CD4+ compared with PBL CD4+ T cells. There was a positive correlation between the
      percentage of BAL lymphocytes and the number of CXCR3 and CCR5 expressing CD4+
      BAL T cells. Also, the number of CD4+ IL-18R+ BAL fluid cells correlated
      negatively with disease duration. CONCLUSIONS: The lung accumulation of CXCR3,
      CCR5, IL-12R and IL-18R expressing T cells is in line with previous reports
      showing elevated levels in the lung of the corresponding ligands in sarcodosis.
      Blocking such ligands and/or receptors may develop into a future immunomodulatory
      therapy.

PMID- 14641798
TI  - Fracture risk associated with smoking: a meta-analysis.
AB  - OBJECTIVES: To assess fracture risk associated with smoking. DESIGN: Systematic
      review. DATA SOURCES: Cohort, case-control, and cross-sectional studies
      identified by searching PubMed and EMBASE, and by recursive screening of
      reference lists. SUBJECTS: Fifty studies including 512 399 subjects were
      included. MAIN OUTCOME MEASURE: Fracture occurrence in current, previous, and
      never smokers. RESULTS: Fracture risk was significantly increased in current
      smokers for all fracture types combined (pooled relative risk 1.26, 95% CI 1.12
      1.42) and for hip (1.39, 95% CI 1.23-1.58) and spine fractures (1.76, 95% CI 1.10
      2.82), but not for wrist fractures (0.86, 95% CI 0.46-1.60). In previous smokers
      the estimate was significantly lower for as well all types of fractures (1.02,
      95% CI 0.85-1.22, P = 0.03 compared with current smokers), as for hip fractures
      (1.19, 95% CI 1.06-1.34, P = 0.04). There was a trend towards higher risk
      estimates in previous smokers for hip fractures in case-control studies than in
      cohort studies. A similar difference between case-control and cohort studies was
      not present for current smokers. There was a geographical heterogeneity: the risk
      of hip fractures associated with current smoking increased with latitude, i.e.
      the risk was higher in Northern Europe and the USA than in Southern Europe and
      countries close to the equator. CONCLUSIONS: Smoking is associated with an
      increased overall fracture risk, an increased risk of hip and spine but not wrist
      fractures. Cessation of smoking seems associated with a decrease in fracture
      risk. The impact of smoking varied geographically with an increase with latitude.

PMID- 14641799
TI  - Aspirin in the prevention of progressing stroke: a randomized controlled study.
AB  - OBJECTIVES: In acute stroke, progression has a severe impact on patient outcome
      and no effective treatment is known. The main objective was to evaluate the
      efficacy of aspirin for prevention of stroke progression thereby improving
      outcome. DESIGN: The trial was randomized, double-blind and placebo-controlled.
      SETTING: The patients were treated in stroke units of four hospitals in Sweden.
      SUBJECTS: Patients with ischaemic stroke but not complete paresis were included.
      No antiplatelet drugs were allowed within the last 72 h before onset. Delay until
      first trial dosage was maximized to 48 h. The trial was designed to detect a 20%
      reduction of the rate of stroke progression, which was estimated to take place in
      20% of cases. Totally, 441 patients (220 aspirin, 221 placebo) completed the
      trial. Baseline comparisons between the groups showed no differences.
      INTERVENTIONS: Aspirin (325 mg) or placebo was given once daily for five
      consecutive days. MAIN OUTCOME MEASURES: Neurological assessments were carried
      out three times daily during the treatment period to detect progression of at
      least two points in the Scandinavian Stroke Supervision Scale. Patient outcome
      was followed up at discharge and at 3 months. RESULTS: Aspirin treatment did not
      significantly reduce the frequency of stroke progression. Amongst aspirin-treated
      patients, stroke progression occurred in 15.9% as compared with 16.7% in the
      placebo group, which is less frequent than expected. The relative risk was 0.95
      (95% CI 0.62-1.45) in the treatment group. As regards patient outcome at
      discharge and after 3 months, aspirin treatment did not show any difference.
      CONCLUSION: No positive effect of aspirin, of the expected size, could be shown
      on the frequency of stroke progression or patient outcome.

PMID- 14641800
TI  - Blunted increase in plasma adenosine levels following dipyridamole stress in
      dilated cardiomyopathy patients.
AB  - BACKGROUND: Heart failure is characterized by chronically increased adenosine
      levels, which are thought to express a protective anti-heart failure activation
      of the adenosinergic system. The aim of the study was to assess whether the
      activation of adenosinergic system in idiopathic dilated cardiomyopathy (IDC) can
      be mirrored by a blunted increase in plasma adenosine concentration following
      dipyridamole stress, which accumulates endogenous adenosine. METHODS: Two groups
      were studied: IDC patients (n = 19, seven women, mean age 60 +/- 12 years) with
      angiographically confirmed normal coronary arteries and left ventricular ejection
      fraction <35%; and normal controls (n = 15, six women, mean age 68 +/- 5 years).
      Plasma adenosine was assessed by high-performance liquid chromatography methods
      in blood samples from peripheral vein at baseline and 12 min after dipyridamole
      infusion (0.84 mg kg-1 in 10 min). RESULTS: At baseline, IDC patients showed
      higher plasma adenosine levels than controls (276 +/- 27 nM L-1 vs. 208 +/- 48 nM
      L-1, P < 0.001). Following dipyridamole, IDC patients showed lower plasma
      adenosine levels than controls (322 +/- 56 nM L-1 vs. 732 +/- 250 nM L-1, P <
      0.001). The dipyridamole-induced percentage increase in plasma adenosine over
      baseline was 17% in IDC and 251% in controls (P < 0.001). By individual patient
      analysis, 18 IDC patients exceeded (over the upper limit) the 95% confidence
      limits for normal plasma adenosine levels at baseline, and all 19 exceeded (below
      the lower limit) the 95% confidence limits for postdipyridamole plasma adenosine
      levels found in normal subjects. CONCLUSION: Patients with IDC have abnormally
      high baseline adenosine levels and--even more strikingly--blunted plasma
      adenosine increase following dipyridamole infusion. This is consistent with a
      chronic activation of the adenosinergic system present in IDC, which can be
      measured noninvasively in the clinical theatre.

PMID- 14641801
TI  - Peroxisome proliferator activated receptor delta genotype in relation to
      cardiovascular risk factors and risk of coronary heart disease in
      hypercholesterolaemic men.
AB  - OBJECTIVES: Peroxisome proliferator activated receptor delta (PPARD) is a
      transcription factor implicated in the regulation of genes involved in
      cholesterol metabolism. We recently discovered a common polymorphism in the 5'
      untranslated region (5'-UTR) of the human PPARD, +294T/C, that is associated with
      an increased plasma low-density lipoprotein cholesterol (LDL-C) concentration in
      healthy subjects. Whether the +294C allele is associated with LDL-C elevation
      independently of the background lipoprotein phenotype and whether it confers
      increased risk of coronary heart disease (CHD) is unknown. Against this
      background, we investigated the relationships between the PPARD polymorphism and
      plasma lipoprotein concentrations and the risk for contracting CHD in the West of
      Scotland Coronary Prevention Study (WOSCOPS). DESIGN: A nested case-control study
      of participants in a randomized double-blind placebo-controlled trial of
      pravastatin in mildly-to-moderately hypercholesterolaemic men. SUBJECTS: A total
      of 580 cases of incident CHD and 1160 individuals who remained free of CHD
      (controls). MAIN OUTCOME MEASURES: Plasma lipoprotein concentrations and risk of
      CHD according to PPARD genotype. RESULTS: Individuals carrying the rare PPARD
      +294C allele had a significantly lower high-density lipoprotein cholesterol (HDL
      C) concentration than subjects homozygous for the common T-allele. Homozygous
      carriers of the C-allele also showed a tendency towards higher risk of CHD
      compared with homozygous carriers of the T-allele. In addition, a gene-gene
      interaction involving the PPARD polymorphism and the PPAR alpha L162V
      polymorphism may influence the plasma LDL-C concentration. CONCLUSIONS: PPARD
      plays a role in cholesterol metabolism in man.

PMID- 14641802
TI  - A young man with a renal colic.
AB  - We report the case of a 35-year-old man with no cardiovascular morbidity,
      presenting with acute flank pain, microscopic haematuria and normal blood
      pressure. Initially diagnosed as a ureteral colic, the patient was recovered 6
      weeks later with severe hypertensive crisis. Further investigations revealed a
      massive renal infarction secondary to medial fibromuscular dysplasia (FMD).
      Several aspects of this presentation are intriguing. Renal infarcts are usually
      seen in older patients having cardiac problems and/or major atheromatous plaques.
      In addition, FMD is mainly observed in young females and rarely progresses to
      renal artery occlusion. Furthermore, in this case, FMD remained silent until the
      acute renal infarction occurred, despite a significant kidney size reduction at
      the time of diagnosis. Finally, the observation of a delayed hypertensive
      response to a major renovascular insult provides incentives to discuss possible
      pathophysiological mechanisms involved in renovascular hypertension.

PMID- 14641804
TI  - Increasing impact.

PMID- 14641805
TI  - Review article: breaking new ground with Rett syndrome.

PMID- 14641806
TI  - Nurse recognition of early deviation in development in home videos of infants
      with Rett disorder.
AB  - BACKGROUND: In the genetic Rett disorder (RD), infants make some progress then
      suffer a dramatic developmental regression, usually before 2 years of age. Home
      videos, taken before the problems are recognized, offer an objective source for
      detecting early signs. METHODS: Thirty-six health visitors and midwives were
      invited to view brief examples from home videos of a cohort of 14 infants with RD
      and 11 control infants with normal development in the first year of life, and to
      indicate, by pressing a button, points in the recordings which aroused their
      suspicion of developmental deviation. They were then invited to comment on their
      selection. The participants were blind as to whether any individual example
      showed an infant with normal development or one with some form of developmental
      disturbance. RESULTS: From the first month of life and throughout the first year,
      infants with RD received more button presses than controls (46%, 361 out of 778
      viewings) in comparison with the control group (12%, 67 of 558). The consistent
      nature of the health professionals' comments made possible their categorization
      under four headings: appearance, posture, movement and contact. In the first
      month of life, the hand postures of infants with RD received particular comment
      from midwives (23 out of 37 comments overall on posture). CONCLUSIONS: The
      present study strongly suggests the presence of early signs of developmental
      deviation in infants with RD, although, in most cases, formal developmental
      screening procedures have failed to detect these before the ages of 12 or 18
      months.

PMID- 14641807
TI  - Validity of a performance assessment of activities of daily living for people
      with developmental disabilities.
AB  - BACKGROUND: Since clients with different types of developmental disabilities
      often experience difficulties in activities of daily living (ADL), it is critical
      that assessments of ADL are evaluated in order to ensure that one can make valid
      judgements based on the results of the appraisal. The purpose of the present
      study was to evaluate the validity of a specific performance assessment
      instrument, the Assessment of Motor and Process Skills (AMPS), when used by
      occupational therapists with clients with developmental disabilities. Unlike
      global ADL assessments, the AMPS is used not only to evaluate the level of ADL
      dependence, but also to estimate the quality of each specific action performed
      when a person is performing ADL tasks. METHODS: Data were gathered from 1724
      participants with different developmental disabilities, including intellectual
      disability (ID), cerebral palsy and spina bifida. Many-Facet Rasch (MFR) analysis
      was used to examine person-response validity, and task and item scale validity.
      RESULTS: Goodness-of-fit statistics showed that the tasks and items had
      acceptable scale validity. The participants had acceptable person-response
      validity on the ADL motor scale, but had slightly lower than expected levels of
      person-response validity on the ADL process scale. The results indicate that
      clients with more severe forms of ID may have a higher proportion of different
      performance profiles in ADL than is expected by the MFR model of the AMPS. Since
      the proportion of participants who did not meet the criteria was only 3% lower
      than expected and in accordance with other studies, the difference may not be
      clinically meaningful. Otherwise, the results indicated that the AMPS is a valid
      tool when used with clients with developmental disabilities. CONCLUSIONS: Further
      research is needed to evaluate the use of the AMPS in clinical assessment and
      intervention planning for this group of clients.

PMID- 14641808
TI  - An audit of investigations into allegations of abuse involving adults with
      intellectual disability.
AB  - BACKGROUND: The present paper describes the results of an audit of referrals to a
      psychology service requesting specialist assistance in the investigation of
      allegations of abuse. METHODS: The referrals were over a 2-year period and case
      notes and records were reviewed to analyse the nature of the allegation, the
      characteristics of the victims or perpetrators, and the process of the
      investigation and its outcome. RESULTS: Twenty-six people were referred for
      investigation into allegations of sexual or physical abuse. The referrals were
      for assistance with an investigative interview (n = 12), capacity to give consent
      to a sexual relationship (n = 8) and competence to give evidence in court (n =
      6). The referrals were all in relation to adults, covering a range of ages and
      degrees of intellectual disability. CONCLUSIONS: The process of the
      investigations suggested that a number of barriers still exist which can make
      decision-making in relation to the alleged abuse extremely difficult. Resolution
      of the allegations through the criminal justice system was also problematic.

PMID- 14641809
TI  - Long-term prognosis of children with Down's syndrome and leukaemia: a 34-year
      nation-wide experience.
AB  - BACKGROUND: Although the characteristics of leukaemia in patients with Down's
      syndrome (DS) have been well documented, little is known about the long-term
      results of treatment. METHOD: Retrospectively from 1968 to 1981 and prospectively
      from 1982 to 2002, the present authors collected data on every child with DS in
      Finland who had been diagnosed with leukaemia between 1968 and 1994. RESULTS:
      Forty-one children with DS had acute leukaemia: 28 had acute lymphoblastic
      leukaemia (ALL); and 13 had acute non-lymphoblastic leukaemia (ANLL). The median
      age of the subjects at diagnosis was 3.8 years (range = 0-15.9 years). Patients
      with ANLL were significantly younger (P = 0.001) and all patients under 2 years
      of age had ANLL. Out of the 28 patients with ALL, 23 (82%) entered primary
      remission, and of these 23 individuals, 10 remained alive and in continuous
      remission (CR) after a median of 11.6 years (range = 8.9-20.0 years). Out of the
      13 patients with ANLL, five (38%) entered remission and four remained in CR after
      a median of 16.0 years (range = 9.1-19.2 years). Treatment -related toxicities
      were common: eight patients with ALL and two with ANLL died of septicaemia.
      Actuarial, event-free survival rates at 5 years were 53% and 43% for adequately
      treated subjects with ALL and ANLL, respectively. CONCLUSIONS: Standard leukaemia
      chemotherapy is effective in patients with DS. However, because toxicities are
      unacceptably frequent, specific anti-leukaemia regimens are needed for subjects
      with DS design.

PMID- 14641810
TI  - Risk factors for self-injurious behaviours among 222 young children with autistic
      disorders.
AB  - The aim of this study was to identify risk factors for self-injurious behaviours
      (SIBs) in children with autistic disorders. The occurrence of SIB was examined in
      comparison with the following variables: chronological age, sex, adaptive skills,
      speech level, associated medical condition, degree of autism and parental social
      class. The subjects were 222 children aged under 7 years and all of them
      fulfilled the ICD-10 criteria for infantile autism. Retrospective data were
      collected on demographic characteristics and medical condition. Children were
      assessed in terms of speech, degree of autism and adaptive skills in
      communication, socialization and daily living skills domains. Results indicated
      that 50% of the children experienced SIB and 14.6% had severe SIBs. Lower
      chronological age, associated perinatal condition, a higher degree of autism and
      a higher daily living skills delay were risk factors of SIBs but parental class,
      sex and epilepsy were not.

PMID- 14641812
TI  - Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories,
      perhaps nutriceuticals and beyond.
AB  - We suggest a putative benefit from timing nutriceuticals (substances that are
      both nutrients and pharmaceuticals) such as antioxidants for preventive or
      curative health care, based on the proven merits of timing nutrients, drugs, and
      other treatments, as documented, i.a., in India. The necessity of timing
      melatonin, a major antioxidant, is noted. A protocol to extend the scope of
      chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader
      time structures, chronomes, for earliest diagnoses, for example detection of
      vascular disease risk, is recommended. The study of rhythms and broader chronomes
      leads to a dynamic functional genomics, guided by imaging in time of free
      radicals and antioxidants, amongst many other variables.

PMID- 14641813
TI  - Modulation of antineoplastic activity of cyclophosphamide by Alstonia scholaris
      in the Ehrlich ascites carcinoma-bearing mice.
AB  - Alterations in the neoplastic activity of cyclophosphamide (CPA) by the extract
      of Alstonia scholaris(ASE) were studied in mice transplanted with Ehrlich ascites
      carcinoma (EAC). The tumor-bearing animals were injected with various doses of
      ASE and 25 mg/kg of CPA (1/10th of the LD50 dose). The combination of 120 mg/kg
      of ASE with 25 mg/kg of CPA was most effective, as it caused the highest tumor
      regression and enhanced the mean survival time (MST) and the average survival
      time (AST) up to 42 and 40.7, as against the 29 and 27.5 of CPA alone,
      respectively. Similarly, when 120 mg/kg of ASE was combined with different doses
      of CPA (3.125 to 50 mg/kg), a dose-dependent increase in the anticancer activity
      was observed up to 25 mg/kg of CPA. However, a further increase in the CPA dose
      up to 37.5 or 50 mg/kg resulted in toxic side effects and death. The best effect
      was observed when 120 mg/kg of ASE was combined with 25 mg/kg followed by 12.5
      mg/kg of CPA, as evident by the greater tumor remission, when compared with the
      concurrent doses of either drug alone. The administration of 120 mg/kg of ASE 6 h
      before the administration of 25 mg/kg of CPA resulted in a drastic decline in the
      glutathione levels and increased the lipid peroxidation considerably when
      compared with either drug alone.

PMID- 14641817
TI  - Cancer prevention and therapy: strategies and problems.
AB  - During the next years, molecular diagnostic science and the pharmaceutical
      industry will face increasing demand for personalized medicine. Therapeutic
      treatments should be tailored to the needs of individual patient. Patients will
      inquire for information about potential tumor detection at an early stage when
      disease can be more likely to be arrested or cured with specific regimens of drug
      therapy. To respond to this demand, science and industry need to modulate
      therapeutic approaches to the continuous development of cancer. Now more than
      ever, it is necessary to fill the knowledge hiatus between the "beginning" and
      the "end" of cancer development, i.e we need to critically analyze the extensive
      multi-step process of cancer development that still remains poorly understood.

PMID- 14641818
TI  - Effects of regulatory domains of specific isoforms of protein kinase C on growth
      control and apoptosis in MCF-7 breast cancer cells.
AB  - Protein kinase C (PKC) is a multigene family consisting of at least 11 isoforms
      that play key roles in growth control and tumorigenesis. To understand the roles
      of specific isoforms of PKC in breast cancer, we generated derivatives of the
      human breast cancer cell line MCF-7 that stably overexpress dominant negative
      mutants (REG) of PKC-alpha, -epsilon, or -zeta, which encode only the regulatory
      domains of the respective isoforms. When stimulated to re-enter the cell cycle
      after serum starvation, the MCF-7/PKC-alpha-REG cell line exhibited enhanced cell
      cycle progression in comparison to the control cell line. These cells also showed
      increased sensitivity to growth inhibition and induction of apoptosis in response
      to various cytotoxic stimuli, including serum starvation, tamoxifen, and gamma
      radiation. Western blot analysis indicated that the MCF-7/PKC-alpha-REG cell line
      displayed marked decreases in the levels of the cyclin-dependent kinase inhibitor
      p21CIP1 and the anti-apoptotic protein bcl-2. Similar, but less striking, effects
      were seen in the MCF-7/PKC-epsilon-REG cell line, and the MCF-7/PKC-zeta-REG cell
      line showed minimal changes, when compared to the control cells. Taken together,
      these results suggest that the endogenous PKC-alpha in MCF-7 cells plays a
      critical role in regulating cell-cycle control and apoptosis, in part through
      upregulating the expression of p21CIP1 and bcl-2. Therefore, inhibitors of PKC
      alpha may potentiate the activity of cytotoxic agents in the therapy of breast
      cancer.

PMID- 14641819
TI  - Modulation of resistance to idarubicin by the cyclosporin PSC 833 (valspodar) in
      multidrug-resistant cells.
AB  - Idarubicin (IDA) is an anthracycline anticancer drug utilized in the treatment of
      acute leukemias. There are conflicting data published with regard to the cross
      resistance of IDA in multidrug-resistant (MDR) cells expressing P-glycoprotein (P
      gp). We evaluated the cytotoxicity and cellular accumulation of IDA in a panel of
      anthracycline-selected MDR cell lines. Leukemia K562/R7 cells and sarcoma MES
      SA/Dx5 cells expressing high levels of the MDR1 (ABCB1) gene were resistant to
      IDA (42-fold and 150-fold, respectively). In both of these cell lines, resistance
      to IDA was equivalent to that for doxorubicin, the drug used to select for the
      MDR variants. The P-gp inhibitor PSC 833 (valspodar) at 2 microM completely
      restored sensitivity to IDA. IDA accumulation was decreased 12-fold in MES-SA/Dx5
      cells vs parental cell line, and drug uptake was restored to control levels by
      PSC 833. Reduced intracellular IDA was correlated with P-gp content by flow
      cytometry. Experiments in NIH3T3 murine cells transfected with the human MDR1
      gene substantiated the findings of cross-resistance to IDA and reversal of
      resistance by PSC 833. Our data indicate that IDA is a high-affinity substrate
      for P-gp.

PMID- 14641820
TI  - Molecular identification and characterization of rat Abcc1 cDNA: existence of two
      splicing variants and species difference in drug-resistance profile.
AB  - The human ABCC1 gene, a member of the ATP-binding cassette transporter super
      family, plays a critical role in conferring cancer cell resistance to
      chemotherapeutic drugs. In the present study, we have cloned the full-length cDNA
      of rat Abcc1 and evaluated its significance in drug resistance. Analysis using
      the currently available genome database revealed that the rat Abcc1 gene is
      located on rat chromosome 13 and consists of at least 30 exons. The rat Abcc1
      cDNA cloned from the spleen was 4981-bp long, within which two additional
      splicing variants were discovered. The rat Abcc1 gene is expressed in a wide
      variety of organs, with the highest expression being observed in the spleen.
      Human embryonic kidney 293 cells were transfected with the rat Abcc1/pcDNA3.1
      vector to stably express rat Abcc1. Overexpression of rat Abcc1 elicited high
      resistance to etoposide. In contrast to the hitherto known drug-resistance
      profile of human ABCC1, rat Abcc1 did not significantly confer cellular
      resistance to anthracyclins or Vinca alkaloids. Our results strongly suggest that
      there is a significant species difference between human ABCC1 and rat Abcc1 in
      their contribution to the drug-resistance profile.

PMID- 14641821
TI  - Andrographolide, a potential cancer therapeutic agent isolated from Andrographis
      paniculata.
AB  - Andrographis paniculata plant extract is known to possess a variety of
      pharmacological activities. Andrographolide, the major constituent of the extract
      is implicated towards its pharmacological activity. We studied the cellular
      processes and targets modulated by andrographolide treatment in human cancer and
      immune cells. Andrographolide treatment inhibited the in vitro proliferation of
      different tumor cell lines, representing various types of cancers. The compound
      exerts direct anticancer activity on cancer cells by cell-cycle arrest at G0/G1
      phase through induction of cell-cycle inhibitory protein p27 and decreased
      expression of cyclin-dependent kinase 4 (CDK4). Immunostimulatory activity of
      andrographolide is evidenced by increased proliferation of lymphocytes and
      production of interleukin-2. Andrographolide also enhanced the tumor necrosis
      factor-alpha production and CD marker expression, resulting in increased
      cytotoxic activity of lymphocytes against cancer cells, which may contribute for
      its indirect anticancer activity. The in vivo anticancer activity of the compound
      is further substantiated against B16F0 melanoma syngenic and HT-29 xenograft
      models. These results suggest that andrographolide is an interesting
      pharmacophore with anticancer and immunomodulatory activities and hence has the
      potential for being developed as a cancer therapeutic agent.

PMID- 14641822
TI  - Abnormal ocular pigment deposition and glaucoma in the dog.
AB  - The combined occurrence of ocular pigment deposition and glaucoma has been
      described in Cairn Terriers. Recently, this condition was also observed in two
      other breeds: the Boxer (two cases) and the Labrador Retriever (one case). Six
      dogs were referred to the Ophthalmology section of the Department of Clinical
      Sciences of Companion Animals and to a private referral clinic because of
      glaucoma or blindness in one or both eyes. In five cases ophthalmic examination
      showed pigment depositions in the sclera around the entire circumference of the
      perilimbal zone. Eight enucleated eyes (four eyes of two Cairn Terriers, three
      eyes of two Boxers and one eye of a Labrador Retriever) were examined
      microscopically. All eyes showed the same findings: an extensive infiltration of
      large melanin-containing cells with an eccentric nucleus, located in the iris,
      ciliary body, retina, choroids and sclera. Transmission electron microscopy of
      two of the examined eyes revealed that the morphology of most of these cells was
      consistent with melanophages. While reports in the veterinary literature
      concerning this condition are limited the cells concerned have been described to
      be melanocytes. Further research is needed to conclusively identify the cell
      type. As described in the present report, the histologic and transmission
      electron microscopic findings suggest a different etiology of the ocular pigment
      deposition and glaucoma compared with the pigment dispersal syndrome in humans.

PMID- 14641823
TI  - Normal ocular features, conjunctival microflora and intraocular pressure in the
      Canadian beaver (Castor canadensis).
AB  - OBJECTIVE: The aim of the study was to assess the ocular features, normal
      conjunctival bacterial and fungal flora, and intraocular pressure (IOP) in the
      Canadian beaver (Castor canadensis). SAMPLE POPULATION: Sixteen, apparently
      healthy beavers with no evidence of ocular disease, and live-trapped in regions
      throughout Prince Edward Island. PROCEDURES: The beavers were sedated with
      intramuscular ketamine (12-15 mg/kg). Two culture specimens were obtained from
      the ventral conjunctival sac of both eyes of 10/16 beavers for aerobic and
      anaerobic bacterial and fungal identifications. The anterior ocular structures of
      all beavers were evaluated using a transilluminator and slit lamp biomicroscope.
      Palpebral fissure length (11/16 beavers), and horizontal and vertical corneal
      diameters (10/16 beavers) were measured. IOPs were measured in both eyes of 11/16
      beavers using applanation tonometry. Both eyes of 3/16 beavers and one eye of
      1/16 beavers were dilated using topical tropicamide prior to sedation to effect
      timely maximal dilation. Culture specimens and IOPs were not evaluated in these
      four animals. Indirect ophthalmoscopy was performed on 7/8 eyes of these four
      beavers. RESULTS: Conjunctival specimens from all eyes cultured positively for
      one or more isolates of aerobic bacteria. The most common isolate was Micrococcus
      spp. (five beavers; 9/20 eyes). Other isolates included a Gram-positive
      coccobacilli-like organism (four beavers; 7/20 eyes), Aeromonas hydrophila (three
      beavers; 4/20 eyes), Staphylococcus spp. (three beavers; 4/20 eyes), Gram
      positive bacilli (one beaver; 2/20 eyes), Enterobacter spp. (two beavers; 2/20
      eyes), Streptococcus spp. (two beavers; 2/20 eyes), aerobic diphtheroids (one
      beaver; 1/20 eyes), and Pseudomonas spp. (one beaver; 1/20 eyes). Clostridium
      sordellii (one beaver; 1/20 eyes) and Peptostreptococcus spp. (one beaver; 1/20
      eyes) were the sole anaerobic bacteria isolated. All conjunctival specimens were
      negative for growth of fungi. Ophthalmic examinations revealed the normal beaver
      eye and ocular adnexa included dorsal and ventral puncta, a vestigial third
      eyelid, and a circular pupil. Average palpebral fissure length was 9.36 mm (SD =
      1.00) for both eyes. Mean horizontal and vertical corneal diameters of both eyes
      were 9.05 mm (SD = 0.64) and 8.45 mm (SD = 0.69), respectively. Mean IOP for the
      right and left eyes were 17.11 mmHg (SD = 6.39) and 18.79 mmHg (SD = 5.63),
      respectively. Indirect ophthalmoscopic examinations revealed normal anangiotic
      retinas. CONCLUSIONS: Gram-positive aerobes were most commonly cultured from the
      conjunctival sac of normal beavers, with Micrococcus spp. predominating. The
      overall mean IOP in ketamine-sedated beavers was 17.95 mmHg. The beaver, an
      amphibious rodent, has an anangiotic retina.

PMID- 14641824
TI  - Effects of topical administration of 1% brinzolamide on normal cat eyes.
AB  - OBJECTIVE: To evaluate the effect of short-term daily topical administration of
      1% brinzolamide on the intraocular pressure (IOP) of healthy domestic cats with
      normotensive eyes and to assess the potential for negative side effects of drug
      administration. ANIMALS: Twelve privately owned adult domestic cats without
      physical or ocular abnormalities. PROCEDURE: Normal variation in IOP was
      determined on day 1. Cats were then treated on days 2-8 with a topical placebo
      (artificial tear solution) OU q 12 h. On days 9-15 the cats were treated q 12 h
      with 1% brinzolamide in one randomly selected eye and the placebo in the
      contralateral eye. All medications (drug and placebo) were administered twice
      daily at 7 a.m. and 7 p.m. On days 16-22 the cats received no topical
      medications. IOP, horizontal pupil size in mm and assessment of conjunctival
      hyperemia were noted OU on days 1, 8, 15 and 22 at 5 time points (9 a.m., 11
      a.m., 1 p.m., 3 p.m. and 5 p.m.). Mixed linear regression models were used to
      compare the IOP of each eye at all time periods for each cat, controlling for age
      and weight. RESULTS: Mean IOP was not significantly altered in any eye at any
      time point during the treatment period compared with pretreatment, baseline, or
      follow-up evaluations. Conjunctival hyperemia and miosis were not detected in
      either eye at any time point. Conclusions and clinical relevance Short-term q 12
      h administration of 1% brinzolamide did not significantly reduce IOP in this
      small sample population of normotensive cats under these study conditions. No
      clinically relevant side effects were noted with brinzolamide administration.

PMID- 14641825
TI  - Superficial, nonhealing corneal ulcers in horses: 23 cases (1989-2003).
AB  - OBJECTIVE: To characterize superficial, nonhealing corneal ulcers in the horse
      and to assess the affect of age, breed, sex, inciting cause of the ulcer, and
      treatment on healing time of these ulcers. DESIGN: Retrospective study. ANIMALS:
      Twenty-three horses with superficial, nonhealing corneal ulcerations. PROCEDURE:
      Medical records from 1989 to 2003 of horses diagnosed with superficial,
      nonhealing corneal ulcers were reviewed. Signalment, duration of clinical signs,
      ophthalmic abnormalities, treatment and response to treatment were recorded.
      Horses were treated, in addition to medical therapy, using debridement,
      debridement and grid keratotomy, superficial keratectomy, and superficial
      keratectomy with conjunctival graft placement. RESULTS: Mean age +/- SD of horses
      was 13.7 +/- 5.8 years. The mean time of presence of the corneal ulceration was
      38.9 +/- 21.3 days. Mean time to complete re-epithelialization of the corneal
      ulcers after treatment was 20 +/- 14.7 days. Horses treated with debridement
      alone, grid keratotomy and superficial keratectomy healed in a mean time of 15.3
      +/- 14.6 days, 16 +/- 12.6 days, and 22.8 +/- 6.7 days, respectively. CONCLUSIONS
      AND CLINICAL RELEVANCE: Horses treated with a single debridement at initial
      evaluation healed in a significantly shorter time period than horses treated with
      grid keratotomy or superficial keratectomy. The latter two procedures may be
      beneficial in the treatment of nonhealing ulceration in horses, but the results
      of this study suggest that these procedures should only be performed following
      failure of the ulcer to heal after epithelial debridement.

PMID- 14641826
TI  - Bartonella vinsonii subspecies berkhoffi as a possible cause of anterior uveitis
      and choroiditis in a dog.
AB  - A 2-year old, neutered, female spaniel mixed breed was referred to the North
      Carolina State University Veterinary Teaching Hospital for evaluation of
      bilateral anterior uveitis. The dog was febrile and, in addition to anterior
      uveitis, multifocal hyporeflective lesions were present in the tapetal fundus of
      both eyes. The antibody titer for Bartonella vinsonii subspecies berkhoffi was
      positive (1 : 512). Aqueous paracentesis was performed for PCR in an attempt to
      detect B. vinsonii in the eye but was unsuccessful. The ocular manifestations of
      Bartonella infection in humans are currently expanding as more sensitive
      serologic and PCR techniques are being developed to identify Bartonella spp. In
      addition to optic neuritis and neuroretinitis, retinochoroidal lesions are one of
      the most common manifestations of B. henselae infection, and are frequently
      accompanied by vitreous or anterior segment inflammation. Diagnosis of a
      Bartonella infection in humans can be made on serology alone, in conjunction with
      ocular examination findings. The ultimate proof of B. vinsonii (berkhoffi) as a
      direct cause of ocular disease would be detection of the infectious agent in the
      eye. However, it is unknown at this time whether Bartonella causes ocular disease
      primarily, secondarily via an autoimmune reaction, or both. Due to the
      difficulties associated with culture of Bartonella spp. and the limitations of
      PCR, serology is currently the most useful tool for screening dogs for possible
      Bartonella spp. infection. In the case presented here, even though the PCR was
      negative, the clinical signs of anterior uveitis and choroiditis might reasonably
      be associated with B. vinsonii (berkhoffi) seroreactivity, which was repeatable
      on three separate occasions. Clinical improvement was also accompanied by a post
      treatment decrease in B. vinsonii (berkhoffi) seroreactivity, potentially
      supporting resolution of Bartonella infection in this dog. This is the first
      reported case of a possible association between uveitis, choroiditis and
      Bartonella infection in the dog, without clinical manifestations of other organ
      or tissue involvement. Future studies based on PCR analysis of intraocular fluids
      may clarify the involvement of B. vinsonii (berkhoffi) in dogs with intraocular
      inflammatory disease. Furthermore, performing fluorescein angiography in dogs
      with elevated Bartonella titers may also prove useful in the identification and
      characterization of lesions.

PMID- 14641827
TI  - Tonometry in adult yellow-footed tortoises (Geochelone denticulata).
AB  - OBJECTIVE: To determine intraocular pressure (IOP) in adult yellow-footed
      tortoises using applanation tonometry. ANIMALS: Fifteen healthy adult captive
      yellow-footed tortoises (eight males and seven females). PROCEDURES: Intraocular
      pressures were estimated for tortoises by using an applanation tonometer after
      topical anesthesia. Body length, measured from nuchal to anal scutes, ranged from
      27.5 to 57.2 cm. Five measurements from each eye were obtained by a single
      observer in an ambient temperature of approximately 30 degrees C. RESULTS: Mean
      +/- SEM IOP of 30 eyes of 15 yellow-footed tortoises was 14.2 +/- 1.2 mmHg. Range
      of IOP was 6-30 mmHg for tortoises. Significant differences were detected neither
      between right and left eyes (P = 0.357) of individual tortoises, nor between
      males and females (P = 0.524). Observer's readability was good (intraclass
      coefficient = 0.65), and IOP did not change over the ordered five measurements.
      CONCLUSIONS: There was no significant difference in IOP between males and females
      in this specie. Tonometry values for normal eyes may represent a useful
      diagnostic methodology for recognition and treatment of ocular diseases in
      reptiles.

PMID- 14641828
TI  - Changes in antibiotic resistance in equine bacterial ulcerative keratitis (1991
      2000): 65 horses.
AB  - OBJECTIVE: To document changes in antibiotic resistance of organisms in cases of
      equine bacterial ulcerative keratitis over a 10-year time period. DESIGN: A
      retrospective study. PARTICIPANTS: Medical records of equine patients with
      bacterial ulcerative keratitis seen at the University of Florida's VMTH for the
      years 1991-2000 were reviewed. MATERIALS AND METHODS: All cases of equine
      bacterial ulcerative keratitis for the above mentioned years were examined.
      Bacterial isolates were identified and subjected to Kirby-Bauer disc diffusion
      method sensitivity tests. Antibiotics used in the sensitivity tests included
      bacitracin, ampicillin, gentamicin, chloramphenicol, polymyxin B, trimethoprim
      sulfa, neomycin, kanamycin, carbenicillin, tobramycin and enrofloxacin. RESULTS:
      A total of 65 bacterial isolates were subjected to sensitivity testing. Of these
      isolates, Pseudomonas aeruginosa accounted for 14 of the bacterial isolates
      (22%), Streptococcus equi subspecies zooepidemicus accounted for 13 of the
      bacterial isolates (20%), and Staphylococcus aureus accounted for four of the
      isolates (6%). A statistically significant increase in resistance of Pseudomonas
      aeruginosa isolates to the antibiotics gentamicin and tobramycin was found
      between the isolates from 1992 to 1998 and those from 1999 to 2000. An increase
      in resistance of Streptococcus equi subspecies zooepidemicus to gentamicin was
      found between the isolates from 1993 to 1997 and those from 1998 to 2000.
      CONCLUSIONS: Streptococcus equi subspecies zooepidemicus and Pseudomonas
      aeruginosa were the most common organisms isolated from cases of equine bacterial
      keratitis referred to the University of Florida's VMTH for the years 1991-2000.
      There appears to be an increase in resistance of Streptococcus equi subspecies
      zooepidemicus to gentamicin over the past 10 years. In addition, there is a
      significant increase in resistance of Pseudomonas aeruginosa to both gentamicin
      and tobramycin over the same time period.

PMID- 14641829
TI  - Effect of topical tropicamide on tear production as measured by Schirmer's tear
      test in normal dogs and cats.
AB  - OBJECTIVE: To evaluate the effect of a single dose of topical 1% tropicamide on
      tear production as measured by the Schirmer tear test (STT) in the normal dog and
      cat. MATERIAL AND METHODS: Twenty-eight dogs and 32 cats received 50 micro l : l
      of 1% tropicamide in one eye and the opposite eye served as the control. STTs
      were performed immediately before instillation of tropicamide and then at 1, 4, 8
      and 24 h post drug instillation. STT results were compared between the control
      and treated eyes at the different times. RESULTS: Aqueous tear production in
      dogs, measured by STT, was not significantly reduced. The mean +/- SEM STTs for
      the baseline time for control and tropicamide-treated eyes were 19.9 +/- 0.8 and
      20.3 +/- 0.8 mm wetting/min, respectively. For the control eyes, the subsequent
      mean +/- SEM STT levels were 20.3 +/- 0.9 (1 h), 21.1 +/- 0.8 (4 h), 20.1 +/- 0.9
      (8 h), and 18.7 +/- 0.7 (24 h). For the tropicamide-treated eyes, the subsequent
      mean +/- SEM STT levels were 19.4 +/- 0.9 (1 h), 19.3 +/- 0.9 (4 h), 20.0 +/- 0.9
      (8 h), and 18.4 +/- 0.8 (24 h). Aqueous tear production of both eyes was
      significantly reduced in cats at 1 h but returned to baseline by 4 h post
      tropicamide instillation. The mean +/- SEM STT levels for the baseline time in
      cats for control and tropicamide-treated eyes were 14.9 +/- 0.8 and 14.7 +/- 0.8
      mm wetting/min, respectively. Subsequent mean +/- SEM STT levels for the control
      eyes were 6.4 +/- 1.1 (1 h), 11.9 +/- 1.0 (4 h), 13.9 +/- 0.8 (8 h), and 16.4 +/-
      1.0 (24 h). For the tropicamide-treated eyes, the subsequent mean +/- SEM STT
      levels were 5.3 +/- 0.8 (1 h), 10.2 +/- 0.8 (4 h), 14.7 +/- 1.0 (8 h), and 16.6
      +/- 1.0 (24 h). CONCLUSION: Single dose 1% tropicamide does not significantly
      lower tear production rates, as measured by the STT, in normal dogs. However, in
      normal cats single doses of 1% tropicamide in one eye cause significant
      reductions in tear production of both eyes at 1 h that recovered to baseline
      levels by 4 h.

PMID- 14641830
TI  - Detection of anti-lens crystallin antibody in dogs with and without cataracts.
AB  - OBJECTIVE: To determine if antilens crystallin (ALC) serum and aqueous humor
      antibodies were present in normal dogs and dogs with cataracts, whether antibody
      incidence varied with stage of cataract, and whether antibody titer had a
      relationship to the presence of lens-induced uveitis. METHODS: Serum and aqueous
      humor samples were obtained from normal dogs and dogs with cataracts. Lens
      crystallin was separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE),
      and antilens crystallin antibodies were detected by Western immunoblot analysis.
      An indirect ELISA using crystallin protein as antigen was also used to detect
      antilens crystallin antibodies in serum and aqueous humor. Test groups included
      normal, incipient, immature, mature, hypermature and diabetic cataract. RESULTS:
      SDS-PAGE identified bands with molecular weights of lens crystallin subunits.
      Western immunoblotting demonstrated reaction between canine serum and these
      protein bands. The five canine serum samples that reacted with crystallin
      subunits on Western blots had corresponding reactivity on the ELISA. All aqueous
      humor samples (30) were negative. Serum ALC antibodies were detected in 59.3%
      (16/27) of controls, 66.7% (16/24) of incipients, 50.0% (10/20) of immatures,
      37.9% (11/29) of matures, 28.6% (6/21) of hypermatures, and 26.7% (4/15) of
      diabetics. Serum ALC antibodies were detected in 43.1% (47/109) of all cataract
      samples. There was a statistically significant negative association between the
      presence (P = 0.004) and maturity (P = 0.004) of cataract and presence of ALC
      serum antibodies. In the immature and hypermature cataract groups, there was a
      statistically significant negative association between ALC serum antibody titer
      and severity of uveitis (95% confidence interval). CONCLUSIONS: There is a
      negative association between the presence (P = 0.004) and maturity (P = 0.004) of
      cataract and presence of ALC serum antibodies.

PMID- 14641831
TI  - The effect of topical administration of atropine sulfate on the normal equine
      pupil: influence of age, breed and gender.
AB  - OBJECTIVES: The purpose of this study was to determine the influence of age,
      breed and gender on vertical pupil diameter (VPD) following a single dose of 1%
      atropine sulfate ophthalmic solution in the normal equine eye. ANIMALS STUDIED:
      Thirty-two horses of various ages, breeds and genders were included. The horses
      had no history or clinical signs of ophthalmic disease. All horses studied had
      darkly pigmented irides. PROCEDURES: Two milligrams of 1% atropine sulfate
      ophthalmic solution was topically administered as a single dose in the right eye
      of each horse on Day 0. The VPD (mm) was measured in both eyes using digital
      calipers prior to treatment and every 24 h after administration for 2 weeks (Days
      1-14). Duration of effect on VPD was then calculated for treated and untreated
      eyes. Data were also analyzed for effect of age, breed and gender on mean VPD,
      maximum VPD and time to maximum VPD. RESULTS: The VPD in the treated eye was
      significantly elevated compared to baseline measurements and compared to the
      untreated eye at all time points. Arabians had a greater mean VPD at Day 0 and on
      several days following treatment. Females had greater mean VPD compared to males
      on 5 out of 15 days. CONCLUSIONS: Duration of mydriasis after administration of
      1% atropine sulfate ophthalmic solution in the normal equine eye is greater than
      14 days. Horses of the Arabian breed and female horses may be more sensitive to
      effects of cholinergic blockade in the eye.

PMID- 14641832
TI  - Orbital cellulitis associated with Toxocara canis in a dog.
AB  - Reports of Toxocara canis ocular larva migrans are uncommon in animals, with only
      a few cases reported. Most reports involve larval migration into the retina and
      choroid, with parasitic invasion of the orbit reported only in experimental
      studies. This is the first clinical case of Toxocara canis infection in the
      retrobulbar region of a 10-year-old, cross-bred male dog presenting with
      unilateral orbital cellulitis. Ophthalmic signs included protrusion of the
      nictitating membrane, chemosis, exophthalmos and hypertropia. The parasite was
      diagnosed by histologic and parasitologic examination of orbital tissues, which
      were removed during enucleation.

PMID- 14641833
TI  - Granulomatous conjunctivitis in an ostrich.
AB  - Ostriches lack meibom glands, but have small lacrimal glands ventral to the
      lateral canthus, with ductules that open into the inside of the lower eyelid.
      Chalazion is a chronic granulomatous inflammation of the meibom glands that may
      develop from blockage of the ductules into the conjunctiva. A 2-year-old female
      ostrich presented with chronic granulomatous conjunctivitis, with clinical and
      histopathologic findings similar to chalazion of other species. The granulomatous
      dacryoadenitic mass was excised and no recurrence occurred at 4 months. This is
      the first case of chronic granulomatous conjunctivitis reported in the ostrich.

PMID- 14641837
TI  - Editorial: One more roast leg of mutton? A novel view of dietary fat.

PMID- 14641838
TI  - Socio-economic factors associated with the purchasing of insecticide-treated nets
      in Afghanistan and their implications for social marketing.
AB  - Malaria is often a major health problem in war-torn countries in the tropics
      owing to the collapse of health services and the vulnerability of displaced
      populations to epidemics. Insecticide-treated nets (ITN) represent one of the few
      options for obtaining protection against malaria in unstable settings deficient
      in health infrastructure. Social marketing of subsidized ITN by a consortium of
      non-governmental organizations began in Afghanistan in 1993 and has continued
      every year since then despite regular political turmoil. Almost 350,000 nets have
      been sold and approximately 1.2 million people protected. In 2000 we examined the
      determinants of ITN purchasing among households in Nangarhar province, eastern
      Afghanistan, as part of an effort to increase ITN uptake. The survey was
      conducted using a structured questionnaire to collect data on socio-economic
      characteristics and malaria beliefs and practices among more than 400 net-owning
      and non-net-owning households. A composite socio-economic index was created using
      principal components analysis, and survey households were divided into socio
      economic quartiles. ITN were 4.5 times more likely to be purchased by families
      from the richest quartile and 2.3 times more likely to be purchased from the
      upper-middle quartile than from the two lower quartiles. Even so, a significant
      minority from the lower quartiles did prioritize and buy ITN. In conflict
      affected countries where livelihoods are compromised, it is necessary to target
      subsidies at the most impoverished to make ITN affordable and to improve overall
      coverage.

PMID- 14641839
TI  - Malaria parasitaemia in relation to HIV status and vitamin A supplementation
      among pre-school children.
AB  - OBJECTIVES: To ascertain whether malaria parasitaemia in children is associated
      with HIV status. To examine the effect of vitamin A supplementation on malaria
      parasitaemia in children. METHODS: We studied the cross-sectional associations
      between HIV status and malaria parasitaemia among 546 children 6-60 months of age
      who participated in a double-blind, randomized clinical trial of vitamin A
      supplementation. Prevalence ratios and 95% confidence intervals (CI) were
      estimated for the presence of malaria parasites at baseline by HIV status in uni-
      and multivariate models that adjusted for sociodemographic and environmental
      variables. Among children with malaria, correlates of high parasite loads were
      identified. Next, we examined the effect of vitamin A supplementation on the risk
      of malaria parasitaemia and high parasite density at 4-8 months of the first dose
      in a subset of children. RESULTS: The prevalence of malaria parasitaemia was
      11.4% among HIV-infected children, compared with 27.6% among uninfected. After
      adjusting for season, anaemia, use of bednets, maternal education and indicators
      of socioeconomic status, we found some evidence for lower prevalence of
      parasitaemia among HIV positive compared with HIV-negative children (prevalence
      ratio=0.56; 95% CI=0.29, 1.09; P=0.09). Other important correlates of malaria
      parasitaemia at baseline included low level of maternal education, poor quality
      of water supply, and the presence of animals at home. Vitamin A supplementation
      did not have a significant effect on malaria parasitaemia at 4-8 months of follow
      up, overall or within levels of potential effect modifiers. CONCLUSION: HIV
      infection appears to be negatively correlated with malaria parasitaemia in this
      group of children. Investing in women's education is likely to decrease the
      prevalence of malaria parasitaemia in children. Vitamin A supplementation does
      not seem to have an effect on malaria parasitaemia in this population; possible
      benefits against clinical episodes and severe malaria deserve further
      examination.

PMID- 14641840
TI  - Prevalence of antibodies to the circumsporozite protein of Plasmodium vivax in
      five different regions of Korea.
AB  - Malaria has recently re-emerged in the Republic of Korea (ROK), but only few
      malaria seroprevalences were reported. We obtained 1014 serum samples from
      inhabitants of five regions of ROK during the high transmission season between
      June and August in 2001. The levels of anti-circumsporozoite protein (CSP)
      antibody were assessed in samples using an indirect enzyme-linked immunosorbent
      assay (ELISA). The highest IgG seroreactivity against Plasmodium vivax
      recombinant CSP antigen was found among male residents of Cheolwon gun (13.5%),
      then Incheon (4.7%). The IgG seroreactivity from other regions ranged from 0.0%
      to 2.0%. These epidemiological data of seroprevalence in five regions of Korea
      showed a similar pattern to the annual incidence of malaria in these respective
      regions. The prevalence of antibodies increased with age, suggesting that the age
      and area-related prevalence patterns reflected differences in the inoculation
      rates between age groups and geographic regions. Seroprevalence and annual
      incidence were positively correlated in some areas of Korea.

PMID- 14641841
TI  - Molecular assessment of drug resistance in Plasmodium falciparum from Bahr El
      Gazal province, Sudan.
AB  - AIMS: To assess resistance to chloroquine (CQ) and sulphadoxine/pyrimethamine
      (SP) in a Sudanese parasite population. METHODS: Recurrent security problems in
      Akuem, Sudan, prevented us from conducting a classical in vivo treatment efficacy
      study. Instead we genotyped key mutations in the chloroquine resistance
      transporter (pfcrt), the multidrug resistance gene (pfmdr1), dihydrofolate
      reductase (dhfr) and dihydropteroate synthase (dhps). We genotyped the K76T
      mutation in pfcrt and the N86Y mutation in (pfmdr) by restriction digestion of
      fluorescent end-labelled polymerase chain reaction (PCR) products, while we
      genotyped codons 16, 51, 59, 108 and 164 in dhfr and codons 436, 437, 540, 581
      and 613 in dhps by primer extension in 100 blood samples. RESULTS: Sixty-three
      percent of parasites carried the 76T mutation at pfcrt critical for CQ
      resistance, while 31% carried the 86Y mutation at pfmdr that is associated with,
      although not essential, for CQ resistance. We found five dhfr alleles: 60% of
      infections contained wild-type dhfr alleles, 3% had one mutation, 34% had two
      mutations, while 3% had three mutations. We found three dhps alleles: 47% were
      wild type, 44% had one mutation, while 9% had two mutations. CONCLUSIONS: We
      expect high levels of treatment failure (RI-RIII) with CQ (20-40%) and predict
      efficient treatment with SP. However, dhfr alleles with three mutations (51I,
      59R, 108N) are present as are dhps alleles with two mutations (437G, 540E).
      Successful treatment with SP is therefore likely to be short-lived.

PMID- 14641842
TI  - Evaluation of the Abbott Cell-Dyn 4000 hematology analyzer for detection and
      therapeutic monitoring of Plasmodium vivax in the Republic of Korea.
AB  - The Cell-Dyn 4000 automated hematology analyzer (CD4000) has the ability to
      detect malaria patients, but it remained unclear whether it could detect
      persistent malaria post-treatment. To investigate this, we used the CD4000 to
      evaluate 68 Korean patients with Plasmodium vivax malaria, and control groups of
      50 patients with fever and 50 asymptomatic patients. The results from the
      instrument-generated scatter plot (derived by laser light depolarization) were
      compared with microscopy results. During the initial diagnosis, the sensitivity
      of the CD4000 in detecting malaria was 91.2%. On day 3 of follow-up, the CD4000
      results matched those from microscopy by 96.7%. Malaria was not detected by
      either method beyond 14 days post-presentation. Interestingly, the atypical
      depolarizing events, which typify the presence of malaria in the analyzer, were
      highly correlated with the levels of parasitaemia in serially diluted samples of
      the leucocyte-depleted blood, and the CD4000 detected parasites down to the level
      of 288 +/- 17.7/microl. Our findings suggest that the phenomenon of atypical
      light depolarization could be influenced by parasitaemia levels, and be used as a
      screening method for P. vivax malaria patients, as well as for the therapeutic
      monitoring.

PMID- 14641843
TI  - The impact of six rounds of single-dose mass administration of diethylcarbamazine
      or ivermectin on the transmission of Wuchereria bancrofti by Culex
      quinquefasciatus and its implications for lymphatic filariasis elimination
      programmes.
AB  - Lymphatic filariasis (LF) is targeted for global elimination. Transmission
      interruption through repeated annual single-dose mass administration of anti
      filarial drugs is the mainstay of the LF elimination strategy. This study
      examined the ability of six rounds of mass administration of diethylcarbamazine
      (DEC) or ivermectin (IVM) to interrupt transmission of Wuchereria bancrofti by
      Culex quinquefasciatus, the predominant parasite and vector species,
      respectively. After six rounds of mass drug administration (MDA), received by 54
      75% of the eligible population (> or =15 kg body weight), the resting vector
      infection and infectivity rates fell by 83% and 79% in the DEC arm, 85% and 84%
      in the IVM arm and 31% and 45% in the placebo arm, respectively. The landing
      vector infection and infectivity rates fell by 83% and 94% in the DEC arm, 63%
      and 75% in the IVM arm and 1% each in the placebo arm, respectively. The filarial
      larval load per resting mosquito declined by 92% and 93% and per landing mosquito
      by 83% and 69% in the DEC and IVM arms, respectively. The annual infective biting
      rate (AIBR) fell from 735 to 93 (87%) in the DEC arm, 422 to 102 (76%) in the IVM
      arm and 472 to 398 (16%) in the placebo arm. The annual transmission potential
      (ATP) declined from 2514 to 125 (95%), 1212 to 241 (80%) and 1547 to 1402 (9%) in
      the DEC, IVM and placebo arms, respectively. However, mosquitoes with infection
      [microfilaria/larva 1/larva 2 (Mf/L1/L2)] were found in all study villages. Three
      of five villages in the IVM arm and two of five in the DEC arm recorded no
      resting mosquitoes with infective-stage (L3) larva. Although the ATP, after six
      rounds of MDA, fell substantially and remained at 125 and 241 in the DEC and IVM
      arms, respectively, the cumulative exposure to infective stage larvae (ATP)
      during the treatment period of 6 years was as high as 2995 in the DEC arm and
      1522 in the IVM arm, because of considerable level of transmission during the
      initial (1-3) rounds of MDA. We conclude that (i) six rounds of MDA, even with 54
      75% treatment coverage, can reduce LF transmission very appreciably; (ii) better
      treatment coverage and a few more rounds of MDA may achieve total interruption of
      transmission; (iii) high vector densities may partly nullify the reductions
      achieved in vector infection and infectivity rates by MDA and (iv) achievement of
      'true zero' Mf prevalence in communities and 0% infection rate (mosquitoes with
      Mf/L1/L2) in mosquitoes may be necessary to totally interrupt Culex-transmitted
      LF.

PMID- 14641844
TI  - Inadvertent exposure of pregnant women to ivermectin and albendazole during mass
      drug administration for lymphatic filariasis.
AB  - The current strategy for the interruption of transmission of lymphatic filariasis
      in areas where the disease is co-endemic with onchocerciasis is repeated annual
      mass treatment of endemic communities with ivermectin and albendazole. These
      drugs are not recommended for use in pregnancy. Pregnant women are excluded on
      the basis of their last menses. This exclusion criterion based on recall carries
      some inherent errors, leading sometimes to inadvertent exposure of foetuses to
      these drugs. This study set out to document the extent of inadvertent exposure of
      pregnant women to albendazole and ivermectin and assess the relative risk of
      congenital malformations because of inadvertent treatment with these drugs in
      early pregnancy. The study was conducted in the Ahanta West District of Ghana.
      Local pregnancy revelation norms were studied, followed by a household survey of
      women aged 15-45 years to assess drug administration coverage. All infants born
      within 42 weeks of the mass drug treatment were examined to document any
      congenital malformations. Mothers who had lost any such infants responded to a
      verbal autopsy to ascertain the probable cause of death. Health facilities and
      local Traditional Birth Attendants were also visited to review maternity records.
      Of 2985 women of childbearing age (15-49 years) who were interviewed, 343 were
      pregnant during the mass drug administration. The sensitivity of the last
      menstrual period in detecting pregnancy and thus being excluded from treatment
      was 0.854 (293 of 343). Some pregnant women 50 of 343 (14.6%) had thus been
      inadvertently treated. This represents 1.7% of women in fertile age group (15-49
      years). Of the six children found with some congenital malformations in these
      communities, one had been exposed to the drugs in-utero. The relative risk for
      congenital malformation after exposure was 1.05 (P=1.0). Two of nine reported
      spontaneous abortions had been exposed to the drugs (P=0.62). We conclude that
      the local mode of excluding pregnancy in the current programme, while not
      perfect, is sufficiently effective and reliable for such a public health
      intervention; and importantly, that there is no evidence of a higher risk of
      congenital malformation or abortions in those who are inadvertently exposed.

PMID- 14641845
TI  - Treatment costs and work time loss due to episodic adenolymphangitis in lymphatic
      filariasis patients in rural communities of Orissa, India.
AB  - OBJECTIVE: To determine the economic loss in terms of treatment costs and loss of
      productive time because of acute episodes of adenolymphangitis (ADL) caused by
      lymphatic filariasis (LF) in a rural population of coastal Orissa, India.
      METHODS: Data on expenditure on treatment and loss of work along with other
      epidemiological information were collected through a 1-year surveillance of 113
      acute episodes of ADL from 72 individuals of the study population (5.42%). The
      activity patterns of patients for 24 h of one episode were documented, and data
      on age- and sex-matched controls were also collected. Standardized Z-test, paired
      t-test, logistic and multiple regressions were used. RESULTS: Those patients who
      did incur expenses spent Indian Rupees 92 on average (approximately US$ 1.85) on
      each episode. The ADL episodes curtailed the productive activity of patients.
      Patients (88%) were unable to attend to any economic activity compared with 47%
      of controls who had no history of disease. Similarly during 55% of episodes,
      females (vs. 8% of controls) could not attend to any domestic work. The mean
      number of hours spent on economic or domestic activities was significantly lower
      among patients. Disease status and sex had significant influence on total
      absenteeism from gainful employment; and similarly, age, family type and disease
      status influenced total domestic work hours among women. CONCLUSIONS: The results
      demonstrate the extent of the economic burden caused by acute LF and provide
      justification for strengthening the ongoing LF elimination programme.

PMID- 14641846
TI  - Interactions between Schistosoma haematobium and Schistosoma mansoni in humans in
      north Cameroon.
AB  - OBJECTIVES: To analyse the relationships between the frequency of ectopic
      localizations of Schistosoma haematobium and S. mansoni eggs. METHODS: Studies
      were conducted in 11 villages in north Cameroon, around Bessoum, a village where
      an epidemic of bloody diarrhoea caused by S. mansoni occurred in 1997. RESULTS:
      The results revealed infection prevalence rates of 70.5% for S. haematobium and
      30.8% for S. mansoni. Interestingly, S. mansoni eggs were found in 14.5% of the
      urine samples and S. haematobium eggs in 3% of the stool samples. These ectopic
      eliminations of schistosome eggs resulted from sexual interactions between the
      two species of schistosomes, and from a spill-over of high infection loads. The
      clinical study showed that the morbidity was lower in individuals with mixed
      infections and high loads of S. haematobium than in those with S. mansoni
      infections only, suggesting a possible lowering effect of S. haematobium
      infection on S. mansoni morbidity. DISCUSSION: The results obtained in human
      populations are discussed in relation to the known schistosome interspecific
      interactions in animal models.

PMID- 14641847
TI  - Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000.
AB  - In the African meningitis belt, the recurrent meningococcal meningitis epidemics
      are generally caused by serogroup A. In the past 20 years, other serogroups have
      been detected, such as X or W135, which have caused sporadic cases or clusters.
      We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X
      that occurred in Niamey between 1995 and 2000. They represented 3.91% of the
      meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A.
      Meningococcal meningitis cases were detected using the framework of the routine
      surveillance system for reportable diseases organized by the Ministry of Public
      Health of Niger. The strains were isolated and determined by the reference
      laboratory for meningitis in Niamey (CERMES) and further typed at the WHO
      collaborating center of the Pharo in Marseille and at the National Reference
      Center for the Meningococci at the Institut Pasteur. Reference laboratories in
      Marseille and Paris characterized 47 isolates having the antigenic formula
      (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to
      meningococcus serogroup X did not present any clinical or epidemiological
      differences to those due to serogroup A. The seasonal incidence was classical;
      93.3% of the cases were recorded during the dry season. The mean age of patients
      was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was
      11.9% without any difference related to age or sex. The increasing incidence of
      the serogroup X was not related to the decrease of serogroup A, but seemed
      cyclic, and evolved independently of the recurrence of both serogroups A and C.

PMID- 14641848
TI  - Application of synthetic peptides to the diagnosis of neurocysticercosis.
AB  - We tested the possible diagnostic utility of five Taenia saginata oncosphere
      derived synthetic peptides in T. solium neurocysticercosis (NC). The five
      peptides correspond to protein sequences with high antigenic indexes that were
      cloned from a T. saginata oncosphere cDNA library. The test samples consisted of
      cerebrospinal fluid (CSF) samples randomly collected from patients referred from
      Mexican and Brazilian neurological institutes. Indirect enzyme-linked
      immunosorbent assays (ELISA) were carried out with the peptides either
      unconjugated or coupled to carrier proteins, and were compared with results
      obtained using T. solium cyst fluid as a positive control. For active
      inflammatory NC, the higher sensibility (93%) and specificity (85%) was obtained
      with peptides HP6-2 and Ts45W-1, respectively, coupled to ovalbumin, in both
      Mexican and Brazilian patients. Examining the results of the individual peptide
      assays in combination, in some instances, improved the sensitivity to 100%.

PMID- 14641849
TI  - Control trial of Lutzomyia longipalpis s.l. in the Island of Margarita,
      Venezuela.
AB  - The incidence of the American visceral leishmaniasis (AVL) in the Island of
      Margarita, a major tourist centre in Venezuela, has been increasing between 1998
      and 2001. Lutzomyia longipalpis s.l. is the recognized vector, which was found
      naturally infected with Leishmania spp, indistinguishable from the parasites
      recovered from dogs and children. In 1999-2000, we conducted a control trial in
      Santa Ana del Valle and Las Cabreras, which have similar epidemiological and
      ecological conditions. The trial was based on intradomestic residual spraying of
      lambda-cyhalothrin, E.C., 25 mg/m2 and spatial fogging of fenitrothion around the
      houses at 30 g/ha. Sandfly abundance was recorded using Centers for Disease
      Control (CDC) traps indoors and outdoors. We found significantly reduced sandfly
      populations in the target locality. Wall bioassays showed that the residual
      effect of the insecticide lasts for about 3 months. We believe that indoor
      spraying with lambda-cyhalothrin three times a year, at a dose slightly greater
      than 25 mg/m2, might reduce the L. longipalpis s.l. population to a level low
      enough for achieving a significant reduction of the indoor transmission, thus
      protecting small children from the disease.

PMID- 14641850
TI  - Detection and characterization of human rotavirus among children with diarrhoea
      in Botswana.
AB  - This study reports the detection, for the first time, of human rotavirus in
      stools of children and the molecular characterization of isolated circulating
      strains in Botswana. We collected 249 stool samples between 1999 and 2001 from
      children with diarrhoea in three health districts of Botswana and examined them
      for the presence of rotavirus antigens and particles. Group A rotavirus antigen
      was detected in 43 of 249 (17%) of the samples tested by enzyme-linked
      immunosorbent assay. Of the 43 children shedding rotaviruses, 37 (86%) were
      infants < or =2 years of age. The presence of rotavirus particles was also
      confirmed by direct electron microscopy. The characteristic 11 segments of the
      double-stranded RNA mobility pattern of rotavirus were demonstrated by
      polyacrylamide electrophoresis in 20 of 43 (47%) of the rotavirus-positive
      samples. The predominant electrophoretic pattern detected was the long (L)
      electrophoretype 14 of 20 (70%) followed by the short (S) electrophoretype five
      of 20 (25%). One strain had a mixed (L/S) pattern. Of the 26 samples subjected to
      subgrouping by enzyme immuno assay, eight were typed as subgroup-II specific and
      seven were subgroup I. The predominant VP7 genotypes detected were G1 (59%). Two
      mixed strains of G1 + G3 (5%) and G1 + G2 (5%) were also detected. VP4 genotypes
      in circulation were: P[4] (5%), P[6] (33%) and P[8] (33%). Mixed P-types P[4 + 6]
      (5%) and P[6 + 8] (18%) were also detected. Rotavirus strains G1 P[8] and GI P[6
      + 8] were the most common cause of diarrhoea in our study area.

PMID- 14641851
TI  - The use of formal and informal curative services in the management of paediatric
      fevers in four districts in Kenya.
AB  - OBJECTIVE: To assess the sources, costs, timing and types of treatment for fevers
      among children under 5 years of age in four ecologically distinct districts of
      Kenya. METHODS: Structured questionnaires were administered to caretakers of one
      randomly selected child aged <5 years per homestead to establish whether the
      child had had a fever within the last 14 days and the types, sources, costs, and
      timing of treatment. Drug charts of common proprietary anti-malarial and
      antipyretic drugs in Kenya were used as visual aids. RESULTS: A total of 2655
      fevers were reported among 6287 (42.2%) children with significant differences
      between the four districts (P<0.01). A substantial number of fevers remained
      untreated (28.1%) across all districts and more fevers were treated in Greater
      Kisii than any other district (P<0.01). The median delay to any treatment was 2
      days [inter-quartile range (IQR): 2, 4]. The informal retail sector had no
      transport costs associated with it and charged less for drugs than all the other
      sectors. Most antimalarial treated fevers occurred in the formal public sector
      (52.6%). Only 2.3% of fevers were treated within 24 h of onset with a sulphur
      pyrimethamine drug, the nationally recommended first-line drug for the management
      of uncomplicated malaria. CONCLUSIONS: The Abuja target of ensuring that 60% of
      childhood fevers are treated with appropriate antimalarial drugs within 24 h of
      onset by 2010 is largely unmet and a major investment in improving prompt access
      to antimalarial drugs will be required to achieve this.

PMID- 14641852
TI  - Short communication: Prevalence of Entamoeba histolytica and Entamoeba dispar in
      northern Ghana.
AB  - Since the redescription of the potentially invasive Entamoeba histolytica,
      separating it from the morphologically identical non-invasive Entamoeba dispar,
      there is a need for the reassessment of epidemiological data on amoebiasis. In
      this context we conducted a descriptive survey on the presence of E. histolytica
      and E. dispar in a rural area in northern Ghana. We found a high prevalence
      (39.8%) of the E. histolytica/E. dispar complex with microscopy, but E.
      histolytica and E. dispar-specific DNA amplification using real-time polymerase
      chain reaction identified only one E. histolytica case and revealed a
      considerably higher prevalence of E. dispar (82.8%).

PMID- 14641853
TI  - Health services analysis as a tool for evidence-based policy decisions: the case
      of the Ministry of Health and Social Security in Mexico.
AB  - OBJECTIVES: To describe the strengths and weaknesses of two Mexican health care
      providers for poor populations [Ministry of Health (MoH) and Social Security
      (SS)] in order to facilitate policy decisions about the future of the two
      systems. METHODOLOGY: In four Mexican states we conducted (i) a household
      interview survey in 10 724 households; (ii) a user satisfaction survey in 1319
      households; (iii) a satisfaction survey of 236 health workers; (iv) in-depth
      interviews with 190 health workers; (v) 188 focus-group discussions with
      different population groups; (vi) a document analysis. RESULTS: Both systems
      serve populations with similar characteristics of poverty. The availability of
      resources was better in the MoH system; SS care was better concerning process
      indicators (family planning, antenatal care; in-service delivery of drugs, staff
      productivity, user satisfaction and staff motivation), efficiency and
      effectiveness (reduction of morbidity and mortality). Possible explanatory
      factors for the better performance of the SS system were strong supervision,
      regular communication, joint data analysis and annual population surveys.
      CONCLUSION: Better service organization makes a difference regarding efficiency
      and effectiveness. Policy-makers, deciding on which kind of health services are
      best for the poor, should take into account health services' analyses.

PMID- 14641856
TI  - Recombinant FVIIa for intractable hemorrhage: more questions than answers.

PMID- 14641857
TI  - Broadening the spectrum of patient groups at risk for transfusion-associated
      GVHD: implications for universal irradiation of cellular blood components.

PMID- 14641858
TI  - Toward a coalition against transfusion-associated GVHD.

PMID- 14641859
TI  - It's time to end RBC shortages.

PMID- 14641860
TI  - Thirty-five years of Rh prophylaxis.

PMID- 14641861
TI  - Transfusion-associated GVHD after fludarabine therapy in a patient with systemic
      lupus erythematosus.
AB  - BACKGROUND: Fludarabine, a purine antimetabolite with potent immunosuppressive
      properties, has previously been associated with the development of transfusion
      associated GVHD (TA-GVHD) in patients with hematologic malignancies. Its role as
      a risk factor for TA-GVHD in patients without underlying leukemia or lymphoma is
      uncertain. STUDY DESIGN AND METHODS: A 42-year-old female with refractory lupus
      nephritis received three monthly cycles of fludarabine (30 mg/m2/day on Days 1-3)
      and cyclophosphamide (500 mg/m2 on Day 1). Three months after the last dose of
      fludarabine, she received 2 units of packed RBCs and 6 units of pooled random
      platelets, none of which were irradiated. Two weeks later, fever, rash,
      aminotransferase elevations, hyperbilirubinemia, and pancytopenia developed.
      RESULTS: Marrow biopsy showed severe aplasia and skin biopsy was consistent with
      GVHD. Allele-level HLA typing on circulating lymphocytes revealed extra HLA
      alleles not present in her pretreatment sample, but identical to the HLA
      haplotypes of an unrelated platelet donor. Treatment with antithymocyte globulin,
      cyclosporine, and prednisone was followed by preparatory conditioning for a PBPC
      transplant from an HLA-identical sibling, but the patient died of disseminated
      candidiasis before transplant. CONCLUSIONS: Fludarabine and other purine analogs
      are increasingly used in the treatment of disorders other than hematologic
      malignancy, such as autoimmune disease. The occurence of TA-GVHD after
      fludarabine therapy in a patient with lupus strongly suggests that this drug is
      sufficiently immunoablative to be an independent risk factor for TA-GVHD.
      Irradiation of blood components should be considered in all patients who receive
      fludarabine therapy.

PMID- 14641862
TI  - Transfusion-associated GVHD: 10 years' experience at the American University of
      Beirut-Medical Center.
AB  - BACKGROUND: Although rare, transfusion-associated GVHD (TA-GVHD) is a fatal
      complication of blood transfusion in which active lymphocytes from the donor
      attack and destroy recipient organs and tissues. STUDY DESIGN AND METHODS: A
      search of patient records was carried out at the American University of Beirut
      Medical Center, looking for patients who developed TA-GVHD over a 10-year period
      extending from 1991 to 2001. Relevant information was collected and analyzed.
      RESULTS: A total of 10 records were found as a result of this search. All were
      immunocompetent and received fresh nonleukoreduced, nonirradiated blood. The
      majority received the transfusion at outside periphery hospitals. They received
      different treatment modalities. The mortality rate was 100 percent. CONCLUSION:
      TA-GVHD is a serious complication with very high mortality. Effective prevention
      guidelines should be established in Lebanon including irradiation and the
      creation of a central blood bank.

PMID- 14641863
TI  - Immunochemical detection of prion protein on dipsticks prepared with crystalline
      bacterial cell-surface layers.
AB  - BACKGROUND: Transmissible spongiform encephalopathy (TSE) represents a spectrum
      of diseases affecting humans and animals. A definitive diagnosis of TSEs is only
      possible by postmortem identification of pathologic prion protein in brain tissue
      that has been treated with protease. The pathologic protein is detected by
      Western blot analysis or ELISA methods. The bovine spongiform encephalopathy
      crisis and occurrence of a new variant of CJD has increased demand for rapid and
      simple assays. STUDY DESIGN AND METHODS: A dipstick assay has been developed for
      prion diagnosis based on a sandwich ELISA specific for prion protein, and
      crystalline bacterial cell-surface layers (S-layers) were used as an
      immobilization matrix. The usefulness of the dipstick assay was evaluated by
      determining the detection limit, comparison with other methods, and analysis of
      CJD samples. RESULTS: The sensitivity of the prion dipsticks was similar to that
      published for time-resolved fluorescence ELISA methods. After protease treatment,
      pathologic prion protein could be detected specifically. CONCLUSION: The dipstick
      assay is a sensitive and specific test useful for the detection of prion protein.
      The simplicity of the S-layer dipstick lends itself to a variety of potential
      applications including field diagnostics.

PMID- 14641864
TI  - TRALI after the transfusion of cross-match-positive granulocytes.
AB  - BACKGROUND: TRALI is a serious complication of transfusion. WBC antibodies have
      been associated with TRALI. The importance of such antibodies for the transfusion
      of granulocytes is unknown. CASE REPORT: A patient with hematologic malignancy
      and neutropenia-associated pneumonitis received 2 units of granulocytes despite a
      positive serologic cross- match. She developed severe TRALI after the second
      transfusion. RESULTS: The recipient's serum was reactive with immobilized HLA
      class I antigens from donor cells in a glycoprotein-specific assay. With an
      absorption-elution technique, at least anti-HLA-A2 could be identified as one of
      the donor-reactive antibodies in the recipient's serum. CONCLUSION: Granulocyte
      reactive antibodies are associated with TRALI in an alloimmunized patient
      receiving granulocyte transfusions. Performing a cross-match procedure may be
      helpful in preventing severe pulmonary reactions. Additional data are required to
      determine whether cross-matching as a regular practice in granulocyte
      transfusions would be beneficial for patients.

PMID- 14641865
TI  - Similar levels of infectivity in the blood of mice infected with human-derived
      vCJD and GSS strains of transmissible spongiform encephalopathy.
AB  - BACKGROUND: The possible transmission of variant CJD (vCJD) through blood
      transfusion or use of plasma-derived products prompted this study comparing
      infectivity in murine models of vCJD and Gerstmann-Straussler-Scheinker (GSS)
      disease, a non-vCJD form of transmissible spongiform encephalopathy (TSE). STUDY
      DESIGN AND METHODS: RIII/Fa/Dk (RIII) or Swiss-Webster (Swiss) mice were
      inoculated intracerebrally (IC) with mouse-adapted strains of vCJD or GSS
      (Fukuoka-1) of similar infectivity. Groups of RIII mice were euthanized 17 weeks
      after inoculation (during the incubation period), and another 23 weeks after
      inoculation (when symptomatic). Blood was collected, separated into components,
      and inoculated into groups of healthy mice; brains and spleens from all mice were
      harvested and tested for the presence of PrPres by Western blot using 6H4 MoAb.
      RESULTS: Levels of 20-30 infectious doses per mL were present in buffy coat and
      plasma during both the incubation and symptomatic stages of disease; PLT pellet
      infectivity was lower (10 ID/mL) and RBCs were not infectious. The disease was
      transmitted more efficiently by IV than IC inoculation of plasma, but there was
      no difference observed with inoculation of buffy coat. The incubation period was
      shorter after IC inoculation of GSS- than vCJD-brain inocula. The amount of
      PrPres in spleens was similar for both TSE agents, but was slightly lower in
      brains of vCJD than GSS mice. CONCLUSION: Infectivity was detected in blood
      components of mice infected with a human-derived strain of vCJD during both the
      preclinical and clinical phases of disease in a similarly low range of
      concentrations as in mice infected with a human-derived nonvariant strain (GSS,
      Fukuoka-1). Other measures of virulence, including brain infectivity titers,
      incubation periods, and the accumulation of PrPres in spleens and brains, were
      also comparable in both experimental models.

PMID- 14641866
TI  - Collection of two units of leukoreduced RBCs from a single donation with a
      portable multiple-component collection system.
AB  - BACKGROUND: A portable automated component collection system that produces double
      (2) units of leukoreduced RBCs (DRBCs) from a single donation was evaluated. This
      study analyzed quality of the collected and final products, the efficacy of
      automated leukoreduction, and donor safety. STUDY DESIGN AND METHODS: The system
      was used to collect 120 DRBCs. WBCs were removed from 90 products with machine
      controlled filtration. DRBCs were collected in ACD-A and stored in AS-1 for 42
      days at 1 to 6 degrees C. Pre- and postprocedure donor vital signs and
      hematologic parameters were measured. Procedure time, product characteristics,
      and adverse events were also recorded. In vitro studies were performed on all
      products on Day 0 and at end of storage. In vivo recoveries of 28 leukoreduced
      and 9 nonleukoreduced products were measured on Day 42. RESULTS: Day 0 mean
      percentage of hemolysis for leukoreduced and nonleukoreduced units was 0.05
      percent. DRBCs had residual WBC counts of less than 1 x 106 cells per unit and
      mean RBC recovery after filtration of 91.9 +/- 2.7 percent. Mean 24-hour recovery
      after infusion for leukoreduced units at end of storage was 80.9 +/- 6.9 percent
      and nonleukoreduced units was 77.6 +/- 5.8 percent (p> 0.05). No clinically
      significant changes in donor vital signs or serious adverse events were observed.
      CONCLUSIONS: The quality of leukoreduced RBCs collected with this portable
      automated component collection system met or exceeded FDA requirements. This
      automated system is safe and effective for collection and processing of 2 units
      of RBCs suitable for transfusion.

PMID- 14641867
TI  - Transcript level of erythroid differentiation-related factor, a candidate
      surrogate marker for transmissible spongiform encephalopathy diseases in blood,
      shows a broad range of variation in healthy individuals.
AB  - BACKGROUND: In 2001, it was demonstrated that the expression of the erythroid
      differentiation-related factor (EDRF) is reduced in lymphatic tissues of rodents
      and cattle as well as in whole blood of sheep that suffer from transmissible
      spongiform encephalopathy. STUDY DESIGN AND METHODS: To determine whether the
      normal range of EDRF expression varies in healthy individuals, mRNA levels were
      measured in whole blood samples from 106 healthy blood donors by quantitative
      real-time RT-PCR. Furthermore, the correlations of transcript levels with
      individual physical characteristics were analyzed. In addition, EDRF expression
      was examined in total RNA samples from a lymph node and the intestine. RESULTS:
      The data show that EDRF mRNA levels in healthy persons vary within a total range
      of 2 log units as well as they display a weak correlation with body height.
      Furthermore, it was found that EDRF is also expressed in lymph nodes and the
      intestine. CONCLUSION: Owing to its broad range of variation, measuring the EDRF
      expression does not seem to be a good surrogate marker, unless an altered
      expression is distinctively different from the varying level in healthy humans.

PMID- 14641868
TI  - Recombinant FVIIa in the management of uncontrolled hemorrhage.
AB  - BACKGROUND: Recombinant FVIIa (rFVIIa/NovoSeven) is a novel hemostatic agent
      originally developed to treat patients with hemophilia who had developed
      inhibitors. Several case reports have suggested that rFVIIa may be effective in
      treating patients without a pre-existing bleeding disorder who have uncontrolled
      bleeding. STUDY DESIGN AND METHODS: Data on the efficacy and safety of rFVIIa in
      the treatment of massive hemorrhage were obtained retrospectively from the
      NovoSeven extended-use data collection system. RESULTS: A total of 40 patients
      received rFVIIa for uncontrolled bleeding, and in these patients, bleeding
      stopped or decreased in 32 (80%). Blood product usage was significantly decreased
      after rFVIIa administration. Thromboembolic events occurred in three patients
      with additional risk factors for thrombosis. Of 40 patients, 23 (57.5%) died.
      Bleeding was the direct cause of death in seven cases (all within 24 hr of
      administration of rFVIIa). The remaining 16 deaths were the result of sepsis,
      multi-organ failure, or the underlying disease. CONCLUSIONS: In this
      retrospective study of data voluntarily submitted to a web-based drug
      surveillance program, we present preliminary results on the use of rFVIIa in
      nonhemophilia patients with bleeding. Although some efficacy is suggested, there
      was a high mortality rate from nonhemorrhagic causes. Randomized controlled
      trials are needed to properly assess the role of rFVIIa in the management of
      hemorrhage.

PMID- 14641869
TI  - Higher Hb level is associated with better early functional recovery after hip
      fracture repair.
AB  - BACKGROUND: The benefits and indications for blood transfusion are controversial.
      One possible reason to transfuse is to improve functional recovery after major
      surgery. However, the data linking improved function with higher Hb concentration
      are limited. STUDY DESIGN AND METHODS: A: retrospective cohort study was
      performed in 5793 patients at least 60 years old undergoing hip fracture repair
      at 20 academic and community hospitals. The primary outcome was distance walked
      at the time of discharge from the hospital. The mean postoperative Hb
      concentration was the main exposure variable and was defined as the average value
      from Day 1 after surgery to discharge. We used robust regression to assess the
      association between postoperative Hb level with distance walked, controlling for
      other preoperative variables that could influence functional recovery. RESULTS:
      On bivariate analysis, the predicted distance walked at discharge in feet (95%
      CI) increased with higher Hb levels (7 g/dL, 56 feet [42-70]; 8 g/dL, 61 feet [54
      68]; 9 g/dL, 67 feet [64-70]; 10 g/dL, 74 feet [72-77]; 11 g/dL, 83 feet [80-85];
      12 g/dL, 92 feet [87-96]). After adjustment for other factors associated with
      ability to walk, higher average postoperative Hb level was independently
      associated with walking greater distance (p < 0.001). CONCLUSIONS: Higher
      postoperative Hb level may improve functional recovery after hip fracture repair.
      If confirmed with clinical trials, this finding would provide a rationale to
      maintain higher Hb concentrations in elderly patients recovering from surgery.

PMID- 14641870
TI  - Evaluation of a new whole-blood filter that allows preparation of platelet
      concentrates by platelet-rich plasma methods.
AB  - BACKGROUND: A novel WBC-reduction in-line whole-blood (WB) filter that does not
      retain platelets was evaluated to assess the filtration performance and, after
      processing WB by the platelet-rich plasma (PRP) method, to analyze the storage
      quality of filtered platelet concentrate (PC) units. STUDY DESIGN AND METHODS: To
      analyze the filter retention, blood was collected from random donors into
      quadruple blood packs with an integral in-line filter (Imuflex WB-SP, Terumo; n =
      25) or in standard triple bag systems (n = 30). To assess the in vitro storage
      characteristics of platelets, 26 WB units were pooled in pairs and redistributed
      into 13 units that underwent WBC reduction and 13 units that were not WBC
      reduced. In all cases, WB was separated into RBCs, PCs, and plasma by the PRP
      method and platelet function was compared. RESULTS: The filtration procedure led
      to RBC and PC WBC-reduced products that met the AABB and European requirements.
      The average filtration time was 30 minutes, the filter retained about 45 mL of
      WB, and there was no further loss of RBCs during the fractionation procedure. In
      vitro PC storage characteristics of the filtered units were similar to those of
      the nonfiltered units. CONCLUSION: A 4- and 3-log WBC reduction was observed in
      RBC and PC units that were produced by the PRP method, with a mean residual WBC
      content of 0.24 +/- 0.38 x 106 and 0.02 +/- 0.03 x 106 per unit, respectively.
      The procedure, performed under relatively simple logistics, results in good
      quality, standard components that may reduce costs and ease the process of WBC
      reduction in transfusion services.

PMID- 14641871
TI  - Molecular bases of the antigens of the Lutheran blood group system.
AB  - BACKGROUND: Lutheran is a complex blood group system consisting of 18 identified
      antigens. There are four pairs of allelic antigens, whereas others are
      independently expressed antigens of a high frequency. Lutheran antigens are
      carried by the Lutheran glycoproteins, which are a product of a single gene LU.
      STUDY DESIGN AND METHODS: Genomic DNA from 21 individuals of 12 Lutheran
      phenotypes was used for PCR amplification of selected LU exons that were directly
      sequenced and compared to control DNA of a common Lutheran phenotype. RESULTS:
      Lutheran phenotypes were mostly caused by single-nucleotide polymorphisms within
      LU, resulting in single amino acid changes. The following mutations were
      observed: in LU:-4, G524A, Arg175Gln; in LU:-5, G326A, Arg109His; in LU:-6,9,
      C824T, Ser275Phe; in LU:-8,14, T611A, Met204Lys; in LU:-13, three point mutations
      (C1340T, Ser447Leu, C1671T silent mutation for Ser557 and A1742T, Gln581Leu); in
      LU:-16, C679T, Arg227Cys; in LU:-17, G340A, Glu114Lys; and in LU:-20, C905T,
      Thr302Met. Two LU:-12 samples had differing results: one individual had a
      deletion 99GCGCTT, Arg34 and Leu35, whereas the second LU:-12 sample had a point
      mutation G419A, Arg140Gln. CONCLUSION: The results revealed the genetic
      background of 11 Lutheran antigens and suggested their placement on the Lutheran
      glycoprotein.

PMID- 14641872
TI  - Mutations in GYPB exon 5 drive the S-s-U+(var) phenotype in persons of African
      descent: implications for transfusion.
AB  - BACKGROUND: The S-s-U- phenotype in African Americans is due to a GYPB deletion,
      however the molecular basis for the S-s-U+var phenotype is poorly understood.
      Variable reactivity of S-s-U+var RBCs with monoclonal anti-He or by anti-U has
      been demonstrated, however the underlying molecular bases for this phenotype
      remain to be established. STUDY DESIGN AND METHODS: Hemagglutination was
      performed on 104 S-s- blood samples using monoclonal anti-He and anti-U. GYPB was
      sequenced from selected samples. Allele and exon-specific PCR analysis was used
      to identify wild-type and mutant alleles. RESULTS: The RBCs of 49-percent S-s-
      samples were identified as S-s-U+var by hemagglutination. Sequencing analysis of
      41 samples revealed 1) a point mutation at +5 (g > t) of intron 5 that resulted
      in skipping of exon 5 in 34 samples; 2) two mutations (208G > T and 230C > T)
      caused partial skipping of exon 5 in four samples due to activation of a cryptic
      3' splice site that resulted from a C > G transversion at nt251 present in all
      GYPB*S alleles and most GYPB*s alleles tested. Three samples were heterozygous
      for the mutated alleles. DISCUSSION: The S-s-U+var phenotype arises from changes
      in or around GYPB exon 5. The weak expression of U and in most examples, He, may
      be due to low levels of normal transcription of the variant gene or to
      posttranscriptional down regulation.

PMID- 14641873
TI  - Applications of DNA-based assays in blood group antigen and antibody
      identification.

PMID- 14641878
TI  - Reflectance spectroscopy can quantify cutaneous haemoglobin oxygenation by oxygen
      uptake from the atmosphere after epidermal barrier disruption.
AB  - BACKGROUND: The supply of oxygen to the viable skin tissue within the upper
      layers is not only secured by the cutaneous blood vascular system, but to a
      significant part also by oxygen diffusion from the atmosphere through the horny
      layer. The aim of this study was to examine whether changes in haemoglobin
      oxygenation can be observed within the isolated perfused bovine udder skin used
      as a skin model by removing the upper horny layer by adhesive tape stripping.
      METHODS: Diffuse reflectance spectroscopy in the visible spectral range was used
      for non-invasive characterisation of haemoglobin oxygenation in skin under in
      vitro conditions. Mid-infrared attenuated total reflectance spectroscopy was
      employed for analysing the surface layer of the stratum corneum with respect to
      keratin, water and lipid components. Skin barrier disruption was achieved by
      repeated stripping of superficial corneocyte layers by adhesive tape. RESULTS AND
      CONCLUSION: Significant changes in skin haemoglobin oxygenation were observed for
      skin areas with reduced lipid concentration and a reduced stratum corneum layer,
      as determined from the quantitative evaluation of the diffuse reflectance skin
      spectra. The result can be interpreted as an increase of oxygen diffusion after
      the removal of the upper horny layer.

PMID- 14641879
TI  - Tribological testing of skin products: gender, age, and ethnicity on the volar
      forearm.
AB  - BACKGROUND/PURPOSE: Few studies have focused on the simultaneous measurement of
      the friction and electrical properties of skin. This work investigates the
      feasibility of using these measurements to differentiate between the effects of
      chemicals commonly applied to the skin. In addition, this study also compares the
      condition of the skin and its response to application of chemicals across gender,
      ethnicity, and age at the volar forearm. METHOD: Friction and electrical tests
      were performed on 59 healthy volunteers with the UMT Series Micro-Tribometer
      (UMT). A 13-mm-diameter copper cylindrical friction/electrical probe was pressed
      onto the skin with a weight of 20 g and moved across the skin at a constant
      velocity of 0.4 mm/s. Each volunteer served as his or her own control. The
      friction and electrical impedance measurements were performed for polyvinylidene
      chloride occlusion and for the application of glycerin and petrolatum. RESULTS:
      No differences were found across age, gender, or ethnicity at the volar forearm.
      Polyvinylidene chloride (PVDC) occlusion showed a small increase in the friction
      and a small decrease in the electrical impedance; petrolatum increased the
      friction by a greater amount but its effect on the impedance was comparable to
      PVDC occlusion; glycerin increased the friction by an amount comparable to
      petrolatum, but it decreased the impedance to a much greater degree than
      petrolatum or the PVDC occlusion. An amplitude/mean measurement of the friction
      curves of glycerin and petrolatum showed that glycerin has a significantly higher
      amplitude/mean than petrolatum. CONCLUSION: The properties of the volar forearm
      appear to be independent of age, gender, and ethnicity. Also, the simultaneous
      measurement of friction and electrical impedance was useful in differentiating
      between compounds administered to the skin.

PMID- 14641880
TI  - The connection between in vitro water uptake and in vivo skin moisturization.
AB  - BACKGROUND/PURPOSE: Humectancy or hygroscopy is the water absorption tendency of
      a substance from the surroundings. Our interest, from the clinical point of view,
      consists of correlating this tendency in vitro and its effect in vivo for the
      development of drugs and formulations for the treatment of dry skin syndrome or
      diseases accompanied by dry skin. METHOD: In vitro, water absorption was measured
      using the comparative isopiestic method. This method is based on bringing the
      vapor of the water to isothermal equilibrium between a reference system and the
      material to be studied. The in vivo model on guinea-pigs for the dry skin
      syndrome tested the therapeutic ability of mono-, di- and tri-glycerols to
      provide moisture to dry skin leading to healing. The moisture content in the
      stratum corneum was measured with a Corneometer CM 825 PC that measures merely
      the presence of high dielectric material (humectant or water), whereas the
      Mexameter MX 16 measures a pathological parameter - the erythema. RESULTS: Adding
      hydroxyl groups to a consecutive set of polyhydroxyalkanes increases the
      humectancy of the polyols in vitro. This elevation was found to be linear at low
      relative humidities (Relative humidity=31.9% and 37 degrees C). In vivo, moisture
      was returned to normal within a week in all three groups. However, only glycerol
      managed to abolish the erythema within 7 days. CONCLUSION: A rise in water
      absorption ability in vitro, at a rate of about 0.25 mol water per hydroxyl group
      was revealed in a consecutive set of glycerols (mono-, di- and tri-glycerols).
      One would expect that the better humectant is a material, i.e. in which the
      higher its physical ability to hold water in vitro the more effective it will be
      in recovering skin dryness. We have found, however, that glycerol, which has the
      lowest humectant activity in vitro, from the set of glycerols, di- and tri
      glycerol, has been proven to be the best for eliminating the signs of skin
      dryness. Accordingly, we propose to distinguish between the in vitro humectancy
      (i.e. the water uptake of a material), and its in vivo moisturizing effect, i.e.
      its ability to cure skin dryness and erythema. This finding supports our
      conclusion that the connection between in vitro humectancy and in vivo
      moisturization is not a simple correlation.

PMID- 14641881
TI  - Geometrical capillary network analysis.
AB  - BACKGROUND: Skin microcirculation, especially the superficial network, can be
      assessed by a computer capillary video microscope system. The study of morphology
      and dynamics of microcirculation must include all dynamic and cooperative
      processes between the capillaries. For characterizing capillary ensembles, the
      statistical and geometrical properties of the network need to be explored.
      METHODS: The microvaculature of the skin and the microcirculation were
      investigated by combining videocapillaroscopy (VCP) and image processing
      techniques based on computational geometry and graph theory. Our goal was to
      characterize the capillary network in noisy pictures of the scalp. Different
      geometric methods were developed, based on proximity parameters (distance and
      surface) in order to circumscribe and construct this network. RESULTS: By
      studying the distribution of these parameters, extreme values or outliers, which
      usually correspond to artifact subregions in the pictures could be eliminated.
      Different algorithms were developed and has been implemented in an image
      processing software (Capilab Toolbox). CONCLUSION: This computerized system is
      capable of real-time processings, increasing the quality of videocapillaroscope
      images and minimizing the disturbance of artifacts. The algorithms presented here
      are easy to implement and can process any kind of images of the skin, even in the
      scalp. In association with an example-based detection system, this method can be
      generalized to other stimuli in the same conditions.

PMID- 14641882
TI  - Assessment of skin viability: is it necessary to use different methodologies?
AB  - BACKGROUND/AIM: Skin is complex and may display variable structural and metabolic
      change 'ex vivo'. The present study aimed to follow measures of skin viability
      and evaluate their usefulness as markers of viability. MATERIALS AND METHODS: We
      evaluated the viability of skin samples fresh or after being frozen and
      subsequently thawed. Assessments included histopathological appearance, lactate
      dehydrogenase (LDH) activity, oxygen consumption and skin pH. RESULTS:
      Morphological investigations of fresh and frozen skin samples using light and
      electron microscopy showed samples with relatively well-defined epidermis and
      dermis. Frozen samples showed some sign of stratum corneum fragmentation,
      although this was not obvious. LDH activity measured in fresh samples kept at 4
      degrees C was low, but it was stable up to 7 days. Fresh samples kept at 32
      degrees C had a comparable LDH activity to the ones kept in the fridge up to 4
      days. Frozen samples, thawed and then kept at 4 degrees C showed a stable LDH
      activity after 24 h of incubation. However, frozen samples incubated at 32
      degrees C demonstrated a high variability in results, with up to 800 U/L of LDH
      activity after 5 days of incubation. Freshly excised as well as freshly thawed
      samples showed the highest respiration rates. Fresh and thawed samples stored for
      a long period of time had a significantly lower (sometimes non-existent) oxygen
      consumption rate. Our results also showed an increase in the oxygen consumption
      rate of fresh samples being incubated at 32 degrees C for 24 h. The oxygen
      consumption rate for all samples reached a plateau within the 15-min measurement
      period and even the fresh samples did not deplete all the oxygen from the medium.
      Skin samples ex vivo showed a significantly higher pH than human skin in vivo,
      and when incubated for 46 h at 32 degrees C, fresh samples had a significantly
      lower pH than frozen samples. All protocols were reproducible and freshly excised
      and freshly thawed skin samples showed the highest rates of viability.
      CONCLUSION: ex vivo skin shows variation of several parameters over time. It is
      recommended to use two or three techniques for evaluation of skin viability
      including at least oxygen measurement and an enzyme assay.

PMID- 14641883
TI  - Skin biophysical properties of a population living in Valais, Switzerland.
AB  - BACKGROUND/PURPOSE: Switzerland has one of the highest rates of skin diseases and
      particularly skin cancer, in Europe. Skin elastosis, roughness and atopy are also
      frequent. High UV exposure and prevalence of light skin individuals could be the
      cause. Valais, in Southern Switzerland, is a mountain region with elevated sun
      irradiation and low air humidity, an ideal location to study the effect of the
      environment and life style on skin biophysical characteristics. The purpose of
      the study was to measure skin biophysical parameters non-invasively on healthy
      subjects living in Valais, and to correlate the measures with their life style.
      METHODS: One hundred and ten women were examined between October 2001 and
      February 2002. Measures of skin hydration, sebum content, pH and visco-elasticity
      were taken in a closed environment with constant temperature and controlled air
      humidity, utilizing commercially available non-invasive devices. Subjects were
      interviewed using a questionnaire and data on personal traits and life style were
      collected. Correlations between subject's skin parameters and life style were
      statistically examined. RESULTS: On average we observed low values of skin
      capacitance that identify subjects with dry skin. Measures of skin visco
      elasticity ratios were also particularly low, while skin pH and sebum content
      were in the normal range. Age was correlated with a decrease of skin elasticity
      and sebum content, but there was no correlation with hydration or pH.
      CONCLUSIONS: We confirm, as reported in other studies, the effect of age on skin
      elasticity and sebum content and we identify, for the first time, a region with a
      population characterized by particularly low levels of skin hydration and skin
      visco-elasticity. Although people examined were free of skin diseases, we believe
      that protection from the sun and treatment of skin with hydrating products need
      to be emphasized as a prevention strategy, in regions such as Valais, with high
      sun irradiation and low humidity.

PMID- 14641884
TI  - Objective assessment of involved surface area in patients with psoriasis.
AB  - BACKGROUND/AIMS: Although difficult, it is essential to assess the disease
      severity of psoriasis objectively. The visual grading method currently used for
      assessing the involved surface area in patients with psoriasis, which is included
      on the Psoriasis Area and Severity Index (PASI) scoring system, is a subjective
      method. The aim of this study was to establish the reliable objective method, in
      estimating the involved surface area in patients with psoriasis. METHODS: Thirty
      patients with psoriasis participated in this study. The skin lesions of each
      patient were estimated using the visual grading method and an image analysis
      system. RESULTS: The differences between five dermatologists' estimates of the
      involved surface area obtained from the visual grading method were highly
      significant (P<0.05, Kruskal-Wallis test). The comparison between the visual
      grading method and the image analysis system showed that the involved areas
      measured by the visual grading method were significantly higher than those from
      the image analysis (P<0.05, Wilcoxon signed rank test). CONCLUSIONS: The visual
      grading method was neither objective nor reproducible. On the other hand, the
      image analysis system can be used as an objective method of measuring the
      involved surface area of patients with psoriasis. Therefore, the image analysis
      system can be used as a standard for the assessment of the involved area of
      patients with psoriasis.

PMID- 14641885
TI  - SkinChip, a new tool for investigating the skin surface in vivo.
AB  - BACKGROUND/AIMS: Non-invasive methods used for characterizing skin micro-relief
      and skin surface hydration were developed in the 1980s. Although they allowed
      some progress in the knowledge of skin properties, they are not completely
      satisfactory in many aspects. Today, new technologies are emerging that may
      address such issues. METHODS: We adapted the technology produced by the ST
      Microelectronics Company for sensing fingerprint for the measurement of skin
      surface properties. Accordingly, we developed acquisition software for obtaining
      routinely the distribution of skin surface capacitance along different body
      sites. Image analysis softwares were also processed for collecting both the main
      orientations of the micro-relief lines and their density. The average value of
      skin capacitance is also obtained. RESULTS: The images allow a highly precise
      observation of the skin topography that can be easily quantified in terms of line
      density and line orientation. The mean gray levels of the images appear much
      closely correlated to the Corneometer values. CONCLUSION: This new device appears
      to be a very convenient way for characterizing the properties of the skin
      surface. With regard to hydration, it usefully provides both the average value
      and the hydration chart of the investigated skin zones.

PMID- 14641886
TI  - Melanoma and seborrheic keratosis differentiation using texture features.
AB  - PURPOSE: To explore texture features in two-dimensional images to differentiate
      seborrheic keratosis from melanoma. METHODS: A systematic approach to consistent
      classification of skin tumors is described. Texture features, based on the second
      order histogram, were used to identify the features or a combination of features
      that could consistently differentiate a malignant skin tumor (melanoma) from a
      benign one (seborrheic keratosis). Two hundred and seventy-one skin tumor images
      were separated into training and test sets for accuracy and consistency.
      Automatic induction was applied to generate classification rules. Data analysis
      and modeling tools were used to gain further insight into the feature space.
      RESULT AND CONCLUSIONS: In all, 85-90% of seborrheic keratosis images were
      correctly differentiated from the malignant skin tumors. The features
      correlation_average, correlation_range, texture_energy_average and
      texture_energy_range were found to be the most important features in
      differentiating seborrheic keratosis from melanoma. Over-all, the seborrheic
      keratosis images were better identified by the texture features than the melanoma
      images.

PMID- 14641888
TI  - Communicating about the risks and benefits of genetically modified foods: the
      mediating role of trust.
AB  - Recent research suggests that public attitudes toward emerging technologies are
      mainly driven by trust in the institutions promoting and regulating these
      technologies. Alternative views maintain that trust should be seen as a
      consequence rather than a cause of such attitudes. To test its actual role,
      direct as well as mediating effects of trust were tested in an attitude change
      experiment involving 1,405 consumers from Denmark, Germany, Italy, and the United
      Kingdom. After prior attitudes to genetic modification in food production had
      been assessed, participants received different information materials (either
      product-specific information or balanced/general information about genetic
      modification in food production) and were asked to evaluate different types of
      genetically modified foods (either beer or yoghurt). The information materials
      were attributed to different information sources (either an industry association,
      a consumer organization, or a government source). After completion, perceived
      risk and perceived benefit were assessed, and participants indicated their trust
      in the information sources to which the materials had been attributed. Direct and
      trust-mediated attitude change effects were estimated in a multi-sample
      structural equation model. The results showed that information provision had
      little effect on people's attitudes toward genetically modified foods, and that
      perceptions of information source characteristics contributed very little to
      attitude change. Furthermore, the type of information strategy adopted had almost
      no impact on postexperimental attitudes. The extent to which people trusted the
      information sources appeared to be driven by people's attitudes to genetically
      modified foods, rather than trust influencing the way that people reacted to the
      information. Trust was not driving risk perception-rather, attitudes were
      informing perceptions of the motivation of the source providing the information.

PMID- 14641887
TI  - Basal electrical impedance in relation to sodium lauryl sulphate-induced skin
      reactions--a comparison of patients with eczema and healthy controls.
AB  - BACKGROUND: Identification of subjects at risk for contact dermatitis by
      screening tests is desirable in order to adjust the preventive measures to
      individual skin susceptibility. The present study aimed to examine the effects of
      basic physiological features, such as baseline electrical impedance (IMP) and
      transepidermal water loss (TEWL), on reactivity to sodium lauryl sulphate (SLS).
      METHODS: On the basis of two previous studies, we re-evaluated the experimental
      irritant skin reactions (50 microL of 2% SLS in large Finn Chambers for 24 h) on
      the volar forearms of 29 patients with eczema and 19 healthy controls. RESULTS:
      We found definite differences in the baseline values of IMP, between the patients
      and the controls. Moreover, patients with eczema showed higher TEWL and lower MIX
      values on day 3 after exposure to SLS, which may indicate differences in SLS
      reactivity. After the study, the biophysical parameters of the eczema patients
      did not return to baseline, which suggests that their skin heals more slowly than
      that of normal subjects. CONCLUSIONS: Our findings indicate that the IMP
      technique may help to 'detect' chemically vulnerable skin. However, more studies
      are needed to determine the value of the basal electrical impedance parameters in
      assessing the risk of developing irritant contact dermatitis.

PMID- 14641889
TI  - Simulation modeling of anthrax spore dispersion in a bioterrorism incident.
AB  - Recent events have increased awareness of the risk posed by terrorist attacks.
      Bacillus anthracis has resurfaced in the 21st century as a deadly agent of
      bioterrorism because of its potential for causing massive civilian casualties.
      This analysis presents the results of a computer simulation of the dispersion of
      anthrax spores in a typical 50-story, high-rise building after an intentional
      release during a bioterrorist incident. The model simulates aerosol dispersion in
      the case of intensive, small-scale convection, which equalizes the concentration
      of anthrax spores over the building volume. The model can be used to predict the
      time interval required for spore dispersion throughout a building after a
      terrorist attack in a high-rise building. The analysis reveals that an aerosol
      release of even a relatively small volume of anthrax spores during a terrorist
      incident has the potential to quickly distribute concentrations that are
      infectious throughout the building.

PMID- 14641890
TI  - Dose-response and risk assessment of airborne hexavalent chromium and lung cancer
      mortality.
AB  - This study evaluates the dose-response relationship for inhalation exposure to
      hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate
      production facility, and provides estimates of the carcinogenic potency. The data
      were analyzed using relative risk and additive risk dose-response models
      implemented with both Poisson and Cox regression. Potential confounding by birth
      cohort and smoking prevalence were also assessed. Lifetime cumulative exposure
      and highest monthly exposure were the dose metrics evaluated. The estimated
      lifetime additional risk of lung cancer mortality associated with 45 years of
      occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was
      0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI:
      0.00143, 0.00302) for the additive risk model assuming a linear dose response for
      cumulative exposure with a five-year lag. Extrapolating these findings to a
      continuous (e.g., environmental) exposure scenario yielded an environmental unit
      risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a
      cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for
      the additive risk model. The relative risk model is preferred because it is more
      consistent with the expected trend for lung cancer risk with age. Based on
      statistical tests for exposure-related trend, there was no statistically
      significant increased lung cancer risk below lifetime cumulative occupational
      exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average
      monthly exposure did not exceed the current Permissible Exposure Limit (52
      microg/m3). It is acknowledged that this study had limited power to detect
      increases at these low exposure levels. These cancer potency estimates are
      comparable to those developed by U.S. regulatory agencies and should be useful
      for assessing the potential cancer hazard associated with inhaled Cr(VI).

PMID- 14641891
TI  - Correlations between parameters in risk models: estimation and propagation of
      uncertainty by Markov Chain Monte Carlo.
AB  - Monte Carlo simulation has become the accepted method for propagating parameter
      uncertainty through risk models. It is widely appreciated, however, that
      correlations between input variables must be taken into account if models are to
      deliver correct assessments of uncertainty in risk. Various two-stage methods
      have been proposed that first estimate a correlation structure and then generate
      Monte Carlo simulations, which incorporate this structure while leaving marginal
      distributions of parameters unchanged. Here we propose a one-stage alternative,
      in which the correlation structure is estimated from the data directly by
      Bayesian Markov Chain Monte Carlo methods. Samples from the posterior
      distribution of the outputs then correctly reflect the correlation between
      parameters, given the data and the model. Besides its computational simplicity,
      this approach utilizes the available evidence from a wide variety of structures,
      including incomplete data and correlated and uncorrelated repeat observations.
      The major advantage of a Bayesian approach is that, rather than assuming the
      correlation structure is fixed and known, it captures the joint uncertainty
      induced by the data in all parameters, including variances and covariances, and
      correctly propagates this through the decision or risk model. These features are
      illustrated with examples on emissions of dioxin congeners from solid waste
      incinerators.

PMID- 14641892
TI  - Prediction of human blood: air partition coefficient: a comparison of structure
      based and property-based methods.
AB  - In recent years, there has been increased interest in the development and use of
      quantitative structure-activity/property relationship (QSAR/QSPR) models. For the
      most part, this is due to the fact that experimental data is sparse and obtaining
      such data is costly, while theoretical structural descriptors can be obtained
      quickly and inexpensively. In this study, three linear regression methods, viz.
      principal component regression (PCR), partial least squares (PLS), and ridge
      regression (RR), were used to develop QSPR models for the estimation of human
      blood:air partition coefficient (logPblood:air) for a group of 31 diverse low
      molecular weight volatile chemicals from their computed molecular descriptors. In
      general, RR was found to be superior to PCR or PLS. Comparisons were made between
      models developed using parameters based solely on molecular structure and linear
      regression (LR) models developed using experimental properties, including
      saline:air partition coefficient (logPsaline:air) and olive oil:air partition
      coefficient (logPolive oil:air), as independent variables, indicating that the
      structure-property correlations are comparable to the property-property
      correlations. The best models, however, were those that used rat logPblood:air as
      the independent variable. Haloalkane subgroups were modeled separately for
      comparative purposes and, although models based on the congeneric compounds were
      superior, the models developed on the complete set of diverse compounds were of
      acceptable quality. The structural descriptors were placed into one of three
      classes based on level of complexity: topostructural (TS), topochemical (TC), or
      three-dimensional/geometrical (3D). Modeling was performed using the structural
      descriptor classes both in a hierarchical fashion and separately. The results
      indicate that highest quality structure-based models, in terms of descriptor
      classes, were those derived using TC descriptors.

PMID- 14641893
TI  - Weighing health benefit and health risk information when consuming sport-caught
      fish.
AB  - Fish consumers may incur benefits and risks from eating fish. Health advisories
      issued by states, tribes, and other entities typically include advice about how
      to limit fish consumption or change other behaviors (e.g., fish cleaning or
      cooking) to reduce health risks from exposure to contaminants. Eating fish,
      however, may provide health benefits. Risk communicators and fish consumers have
      suggested the importance of including risk comparison information, as well as
      health risk-benefit comparisons in health advisory communications. To improve
      understanding about how anglers fishing in waters affected by health advisories
      may respond to such risk-risk or risk-benefit information, we surveyed Lake
      Ontario (NY, USA) anglers. We interviewed by telephone 4,750 anglers, 2,593 of
      which had fished Lake Ontario in the past 12 months and were sent a detailed mail
      questionnaire (1,245 responded). We posed questions varying the magnitude of
      health risks and health benefits to be gained by fish consumption, and varied the
      population affected by these risks and benefits (anglers, children, women of
      childbearing age, and unborn children). Respondents were influenced by health
      benefit and health risk information. When risks were high, most respondents would
      eat less fish regardless of the benefit level. When risks were low, the magnitude
      of change in fish consumption was related to level of benefit. Responses differed
      depending on the question wording order, that is, whether "risks" were posed
      before "benefits." For a given risk-benefit level, respondents would give
      different advice to women of childbearing age versus children, with more
      conservative advice (eat less fish) provided to women of childbearing age.
      Respondents appeared to be influenced more strongly by risk-risk comparisons
      (e.g., risks from other foods vs. risks from fish) than by risk-benefit
      comparisons (e.g., risks from fish vs. benefits from fish). Risk analysts and
      risk communicators should improve efforts to include risk-risk and risk-benefit
      comparisons in communication efforts, and to clarify to whom the health risks and
      benefits from fish consumption may accrue.

PMID- 14641894
TI  - Health risk assessment after decontamination of the beaches polluted by the
      wrecked ERIKA tanker.
AB  - Following the wreck of the oil tanker ERIKA off the north-west coast of France in
      December 1999, cleaning up of the beaches involved considerable work, which in
      any case could not be perfect. This raised the question of the short- and long
      term health risks for the future bathers related to the toxicity of the remaining
      oil polycyclic aromatic hydrocarbons (PAHs). This risk assessment study was
      conducted to help health authorities plan risk management policies and inform the
      public. Thirty-six beaches were selected, representing a sample of the most
      frequently encountered topographic and beach usage situations; seven "control"
      beaches, unspoiled by ERIKA, were also investigated. Samples of water and sand
      were taken from each site, as well as from the surface of rocks. The 16 PAHs
      selected by the U.S. EPA were quantified in each environment. Several scenarios
      of exposure were contemplated: (1) a child between 2 and 4 years accidentally
      ingesting a small ball of fuel, (2) a child daily exposed throughout his holiday
      time stay, (3) an adult (including a pregnant woman) spending his/her holidays on
      the coast, (4) an adult working on the beach, (5) and an adult practicing water
      sports. Among the available and significant toxicological values, the most
      conservative ones were selected for computing risks. The sand and water, after
      decontamination, were slightly polluted (respectively, 7.8 microg/kg and 23.3
      ng/l of total 16 PAHs), with values similar to those found in the control
      beaches. By contrast, the rocky areas in some places were still highly polluted
      (up to 23 mg/kg on the surface layer). No lethal risk was found for a young child
      who had accidentally ingested a small ball of fuel. The life-long excess risks
      for skin cancer and for all other cancers were about 10-5 in scenarios including
      contact with the polluted rocks. In all other cases, excess risks were
      considerably lower. The hazard quotient for teratogenic effects was very small,
      except in scenarios where pregnant women would walk among rocks containing high
      pollution levels. In conclusion, exposure was mainly associated with polluted
      water among children, and with spoiled rocks for adults. Despite uncertainties,
      mainly dealing with the prediction of long-term risks following a short-term
      exposure, this study showed that beaches where pollution was no longer visible
      after decontamination did not entail any significant health risks and could be
      opened to the public.

PMID- 14641896
TI  - A model for optimization of biomarker testing frequency to minimize disease and
      cost: example of beryllium sensitization testing.
AB  - A common problem with medical surveillance programs using biomarkers is
      determining the optimal frequency of testing to minimize adverse health effects
      and cost. In the case of beryllium-exposed workers, frequency of testing for
      beryllium sensitization may be especially important. Recent studies indicate a
      lack of dose response for beryllium sensitization, but do support a dose response
      for the development of chronic beryllium disease (CBD). Though unproven, this
      implies that early identification of sensitization and immediate removal from
      exposure may reduce development of CBD. A model is proposed to project the
      optimal frequency of sensitization testing using the current beryllium lymphocyte
      proliferation test (BeLPT) to minimize disease-related costs, assuming that a
      positive BeLPT will precede CBD. Conversion rates for cumulative exposure to
      disease development were adapted from the literature and used with testing costs
      and cost of disease estimates in the model. The model was run assuming several
      test frequency regimes. Results support the use of periodic testing in line with
      the annual schedule proposed in the Final Chronic Beryllium Disease Prevention
      Program Rule (1999) following initial testing within three months of first
      beryllium exposure. The financial and health benefits of reducing the time from
      exposure to detection of early disease was also explored with the model and
      demonstrated as a highly desirable characteristic for an alternative test or
      improved BeLPT. Limitations of the approach are discussed as well as options for
      adapting this biomarker optimization methodology to consider biomarkers of other
      exposure-associated diseases.

PMID- 14641897
TI  - The impact of cytochrome P450 2E1-dependent metabolic variance on a risk-relevant
      pharmacokinetic outcome in humans.
AB  - Risk assessments include assumptions about sensitive subpopulations, such as the
      fraction of the general population that is sensitive and the extent that
      biochemical or physiological attributes influence sensitivity. Uncertainty
      factors (UF) account for both pharmacokinetic (PK) and pharmacodynamic (PD)
      components, allowing the inclusion of risk-relevant information to replace
      default assumptions about PK and PD variance (uncertainty). Large numbers of
      human organ donor samples and recent advances in methods to extrapolate in vitro
      enzyme expression and activity data to the intact human enable the investigation
      of the impact of PK variability on human susceptibility. The hepatotoxicity of
      trichloroethylene (TCE) is mediated by acid metabolites formed by cytochrome P450
      2E1 (CYP2E1) oxidation, and differences in the CYP2E1 expression are hypothesized
      to affect susceptibility to TCE's liver injury. This study was designed
      specifically to examine the contribution of statistically quantified variance in
      enzyme content and activity on the risk of hepatotoxic injury among adult humans.
      We combined data sets describing (1) the microsomal protein content of human
      liver, (2) the CYP2E1 content of human liver microsomal protein, and (3) the in
      vitro Vmax for TCE oxidation by humans. The 5th and 95th percentiles of the
      resulting distribution (TCE oxidized per minute per gram liver) differed by
      approximately sixfold. These values were converted to mg TCE oxidized/h/kg body
      mass and incorporated in a human PBPK model. Simulations of 8-hour inhalation
      exposure to 50 ppm and oral exposure to 5 micro g TCE/L in 2 L drinking water
      showed that the amount of TCE oxidized in the liver differs by 2% or less under
      extreme values of CYP2E1 expression and activity (here, selected as the 5th and
      95th percentiles of the resulting distribution). This indicates that differences
      in enzyme expression and TCE oxidation among the central 90% of the adult human
      population account for approximately 2% of the difference in production of the
      risk-relevant PK outcome for TCE-mediated liver injury. Integration of in vitro
      metabolism information into physiological models may reduce the uncertainties
      associated with risk contributions of differences in enzyme expression and the UF
      that represent PK variability.

PMID- 14641898
TI  - Probabilistic framework for the estimation of the adult and child toxicokinetic
      intraspecies uncertainty factors.
AB  - Human health risk assessments use point values to develop risk estimates and thus
      impart a deterministic character to risk, which, by definition, is a probability
      phenomenon. The risk estimates are calculated based on individuals and then,
      using uncertainty factors (UFs), are extrapolated to the population that is
      characterized by variability. Regulatory agencies have recommended the
      quantification of the impact of variability in risk assessments through the
      application of probabilistic methods. In the present study, a framework that
      deals with the quantitative analysis of uncertainty (U) and variability (V) in
      target tissue dose in the population was developed by applying probabilistic
      analysis to physiologically-based toxicokinetic models. The mechanistic
      parameters that determine kinetics were described with probability density
      functions (PDFs). Since each PDF depicts the frequency of occurrence of all
      expected values of each parameter in the population, the combined effects of
      multiple sources of U/V were accounted for in the estimated distribution of
      tissue dose in the population, and a unified (adult and child) intraspecies
      toxicokinetic uncertainty factor UFH-TK was determined. The results show that the
      proposed framework accounts effectively for U/V in population toxicokinetics. The
      ratio of the 95th percentile to the 50th percentile of the annual average
      concentration of the chemical at the target tissue organ (i.e., the UFH-TK)
      varies with age. The ratio is equivalent to a unified intraspecies toxicokinetic
      UF, and it is one of the UFs by which the NOAEL can be divided to obtain the
      RfC/RfD. The 10-fold intraspecies UF is intended to account for uncertainty and
      variability in toxicokinetics (3.2x) and toxicodynamics (3.2x). This article
      deals exclusively with toxicokinetic component of UF. The framework provides an
      alternative to the default methodology and is advantageous in that the evaluation
      of toxicokinetic variability is based on the distribution of the effective target
      tissue dose, rather than applied dose. It allows for the replacement of the
      default adult and children intraspecies UF with toxicokinetic data-derived values
      and provides accurate chemical-specific estimates for their magnitude. It shows
      that proper application of probability and toxicokinetic theories can reduce
      uncertainties when establishing exposure limits for specific compounds and
      provide better assurance that established limits are adequately protective. It
      contributes to the development of a probabilistic noncancer risk assessment
      framework and will ultimately lead to the unification of cancer and noncancer
      risk assessment methodologies.

PMID- 14641899
TI  - Public meetings and risk amplification: a longitudinal study.
AB  - This article offers longitudinal data tracking people who did and did not attend
      a series of public meetings in an upstate New York rural community grappling with
      the expansion of an existing solid waste landfill and remediation of an adjacent
      inactive hazardous waste site. Before and after the public meetings, mailed
      questionnaires measured risk perceptions and perceived credibility of risk
      managers (here, the state government agencies and the responsible industry)
      conducting the meetings. Respondents at each measurement point included meeting
      attendees and nonattendees, with some fluctuation over time when attendees at one
      measurement point were nonattendees at the next and vice versa. The results from
      the first survey indicate that following the first two public meetings, attendees
      perceived greater risks from the waste sites than did nonattendees; attendees
      also perceived the risk managers as less credible. After the third public
      meeting, the results showed that attendees' risk perceptions remained steady;
      however, perceptions of government agency credibility significantly decreased.
      After the fourth public meeting, the survey found that attendees' risk
      perceptions were again not significantly different, whereas perceptions of
      government agency credibility increased significantly. The industry's credibility
      also increased, though only among attendees who had attended the most recent
      public meeting, not among attendees who had attended both the third and fourth
      public meetings. For nonattendees, risk perceptions and credibility ratings did
      not change. The discussion examines how distinctive characteristics of
      communication at each public meeting may have resulted in different effects and
      proposes hypotheses for future research.

PMID- 14641900
TI  - Risk perception in a developing country: the case of Chile.
AB  - In this work we characterize risk perception in Chile, based on the psychometric
      paradigm, exploring the difference between perceived social and personal risk.
      For this purpose, we conducted a survey including 54 hazards, 16 risk attributes,
      and 3 risk constructs. The survey, divided into four parts, was administered to
      508 residents of Santiago, Chile. Using factor analysis, three main factors,
      which accounted for 80% of the sample's variance, were identified: factor 1,
      commonly called "Dread Risk" in the literature, explained 37% of variance; factor
      2, "Unknown Risk," explained 28%; and factor 3, which we called "Personal
      Effect," explained 15% of the variance. On average, individuals perceived
      themselves as less exposed to risk and with more control and knowledge about them
      than the general population. OLS regression models were used to test the
      association of perceived risk with the three main factors. For social risk,
      factor 1 had the greatest explanatory power, while factor 2 had a negative sign.
      For personal risk, only factors 2 and 3 were significant, with factor 3 having
      the greatest explanatory power. Risk denial (defined as the difference between
      perceived personal and social risk) was associated with factors 1 and 2 only,
      with factor 2 having a negative sign. The difference between desired and actual
      regulation levels proved positive for all hazards, thus indicating that Chileans
      are dissatisfied with the current regulation level for all the hazards analyzed.
      The comparison of data at the aggregate and at the individual subject's level
      suggests that while the aggregate analysis overestimates the magnitude of the
      correlations it still reflects the tendency of the individual responses.

PMID- 14641901
TI  - Risk communication and foodborne illness: message sponsorship and attempts to
      stimulate perceptions of risk.
AB  - Foodborne illness represents a serious health hazard in the United States. Since
      foodborne illness can often be prevented by an individual's behavior, messages
      aimed at promoting safe food-handling behaviors should be a major tool to reduce
      the incidence of foodborne illness. This article argues that to achieve adoption
      of safe food-handling practices in the home, food-safety messages should both
      stimulate risk perceptions and promote self-efficacy, feelings that one can
      successfully enact recommended behaviors. A content analysis of nationally
      distributed food-safety messages questioned if messages incorporated these
      features. Since food-safety communicators operate in complex environments with
      multiple and sometimes competing objectives, this study also questioned if
      sponsorship of foodborne illness prevention messages was related to the amount of
      content designed to alter risk perceptions associated with foodborne illness.
      Results of the quantitative content analysis found that copywriters generally
      included content designed to stimulate risk perception about foodborne illness
      but virtually ignored self-efficacy needs of the audience. A marked difference in
      tendencies to stimulate risk perceptions was found based on sponsorship. Both in
      volume and proportion, results show that governmentally sponsored messages more
      aggressively attempted to heighten risk perceptions associated with foodborne
      illness than did messages sponsored by privately funded communicators.

PMID- 14641902
TI  - Model uncertainty and choices made by modelers: lessons learned from the
      International Atomic Energy Agency model intercomparisons.
AB  - The treatment of uncertainties associated with modeling and risk assessment has
      recently attracted significant attention. The methodology and guidance for
      dealing with parameter uncertainty have been fairly well developed and
      quantitative tools such as Monte Carlo modeling are often recommended. However,
      the issue of model uncertainty is still rarely addressed in practical
      applications of risk assessment. The use of several alternative models to derive
      a range of model outputs or risks is one of a few available techniques. This
      article addresses the often-overlooked issue of what we call "modeler
      uncertainty," i.e., difference in problem formulation, model implementation, and
      parameter selection originating from subjective interpretation of the problem at
      hand. This study uses results from the Fruit Working Group, which was created
      under the International Atomic Energy Agency (IAEA) BIOMASS program (BIOsphere
      Modeling and ASSessment). Model-model and model-data intercomparisons reviewed in
      this study were conducted by the working group for a total of three different
      scenarios. The greatest uncertainty was found to result from modelers'
      interpretation of scenarios and approximations made by modelers. In scenarios
      that were unclear for modelers, the initial differences in model predictions were
      as high as seven orders of magnitude. Only after several meetings and discussions
      about specific assumptions did the differences in predictions by various models
      merge. Our study shows that parameter uncertainty (as evaluated by a
      probabilistic Monte Carlo assessment) may have contributed over one order of
      magnitude to the overall modeling uncertainty. The final model predictions ranged
      between one and three orders of magnitude, depending on the specific scenario.
      This study illustrates the importance of problem formulation and implementation
      of an analytic-deliberative process in risk characterization.

PMID- 14641903
TI  - Distribution of arsenic and copper in sediment pore water: an ecological risk
      assessment case study for offshore drilling waste discharges.
AB  - Due to the hydrophobic nature of synthetic based fluids (SBFs), drilling cuttings
      are not very dispersive in the water column and settle down close to the disposal
      site. Arsenic and copper are two important toxic heavy metals, among others,
      found in the drilling waste. In this article, the concentrations of heavy metals
      are determined using a steady state "aquivalence-based" fate model in a
      probabilistic mode. Monte Carlo simulations are employed to determine pore water
      concentrations. A hypothetical case study is used to determine the water quality
      impacts for two discharge options: 4% and 10% attached SBFs, which correspond to
      the best available technology option and the current discharge practice in the
      U.S. offshore. The exposure concentration (CE) is a predicted environmental
      concentration, which is adjusted for exposure probability and bioavailable
      fraction of heavy metals. The response of the ecosystem (RE) is defined by
      developing an empirical distribution function of predicted no-effect
      concentration. The pollutants' pore water concentrations within the radius of 750
      m are estimated and cumulative distributions of risk quotient (RQ=CE/RE) are
      developed to determine the probability of RQ greater than 1.

PMID- 14641904
TI  - Risk modeling, assessment, and management of lahar flow threat.
AB  - The 1991 eruption of Mount Pinatubo in the Philippines is considered one of the
      most violent and destructive volcanic activities in the 20th century. Lahar is
      the Indonesian term for volcanic ash, and lahar flows resulting from the massive
      amount of volcanic materials deposited on the mountain's slope posed continued
      post-eruption threats to the surrounding areas, destroying lives, homes,
      agricultural products, and infrastructures. Risks of lahar flows were identified
      immediately after the eruption, with scientific data provided by the Philippine
      Institute of Volcanology, the U.S. Geological Survey, and other research
      institutions. However, competing political, economic, and social agendas
      subordinated the importance of scientific information to policy making. Using
      systemic risk analysis and management, this article addresses the issues of
      multiple objectives and the effective integration of scientific techniques into
      the decision-making process. It provides a modeling framework for identifying,
      prioritizing, and evaluating policies for managing risk. The major considerations
      are: (1) applying a holistic approach to risk analysis through hierarchical
      holographic modeling, (2) applying statistical methods to gain insight into the
      problem of uncertainty in risk assessment, (3) using multiobjective trade-off
      analysis to address the issue of multiple decisionmakers and stakeholders in the
      decision-making process, (4) using the conditional expected value of extreme
      events to complement and supplement the expected value in quantifying risk, and
      (5) assessing the impacts of multistage decisions. Numerical examples based on ex
      post data are formulated to illustrate applications to various problems. The
      resulting framework from this study can serve as a general baseline model for
      assessing and managing risks of natural disasters, which the Philippines' lead
      agency-the National Disaster Coordinating Council (NDCC)-and other related
      organizations can use for their decision-making processes.

PMID- 14641905
TI  - Comparative risk and policy analysis in environmental health.
AB  - There is increasing interest in the integration of quantitative risk analysis
      with benefit-cost and cost-effectiveness methods to evaluate environmental health
      policy making and perform comparative analyses. However, the combined use of
      these methods has revealed deficiencies in the available methods, and the lack of
      useful analytical frameworks currently constrains the utility of comparative risk
      and policy analyses. A principal issue in integrating risk and economic analysis
      is the lack of common performance metrics, particularly when conducting
      comparative analyses of regulations with disparate health endpoints (e.g., cancer
      and noncancer effects or risk-benefit analysis) and quantitative estimation of
      cumulative risk, whether from exposure to single agents with multiple health
      impacts or from exposure to mixtures. We propose a general quantitative framework
      and examine assumptions required for performing analyses of health risks and
      policies. We review existing and proposed risk and health-impact metrics for
      evaluating policies designed to protect public health from environmental
      exposures, and identify their strengths and weaknesses with respect to their use
      in a general comparative risk and policy analysis framework. Case studies are
      presented to demonstrate applications of this framework with risk-benefit and air
      pollution risk analyses. Through this analysis, we hope to generate discussions
      regarding the data requirements, analytical approaches, and assumptions required
      for general models to be used in comparative risk and policy analysis.

PMID- 14641908
TI  - A DNA element recognised by the molybdenum-responsive transcription factor ModE
      is conserved in Proteobacteria, green sulphur bacteria and Archaea.
AB  - BACKGROUND: The transition metal molybdenum is essential for life. Escherichia
      coli imports this metal into the cell in the form of molybdate ions, which are
      taken up via an ABC transport system. In E. coli and other Proteobacteria
      molybdenum metabolism and homeostasis are regulated by the molybdate-responsive
      transcription factor ModE. RESULTS: Orthologues of ModE are widespread amongst
      diverse prokaryotes, but not ubiquitous. We identified probable ModE-binding
      sites upstream of genes implicated in molybdenum metabolism in green sulphur
      bacteria and methanogenic Archaea as well as in Proteobacteria. We also present
      evidence of horizontal transfer of nitrogen fixation genes between green sulphur
      bacteria and methanogenic Archaea. CONCLUSIONS: Whereas most of the archaeal
      helix-turn-helix-containing transcription factors belong to families that are
      Archaea-specific, ModE is unusual in that it is found in both Archaea and
      Bacteria. Moreover, its cognate upstream DNA recognition sequence is also
      conserved between Archaea and Bacteria, despite the fundamental differences in
      their core transcription machinery. ModE is the third example of a
      transcriptional regulator with a binding signal that is conserved in Bacteria and
      Archaea.

PMID- 14641909
TI  - Identification and phylogenetic analysis of Dictyostelium discoideum kinesin
      proteins.
AB  - BACKGROUND: Kinesins constitute a large superfamily of motor proteins in
      eukaryotic cells. They perform diverse tasks such as vesicle and organelle
      transport and chromosomal segregation in a microtubule- and ATP-dependent manner.
      In recent years, the genomes of a number of eukaryotic organisms have been
      completely sequenced. Subsequent studies revealed and classified the full set of
      members of the kinesin superfamily expressed by these organisms. For
      Dictyostelium discoideum, only five kinesin superfamily proteins (Kif's) have
      already been reported. RESULTS: Here, we report the identification of thirteen
      kinesin genes exploiting the information from the raw shotgun reads of the
      Dictyostelium discoideum genome project. A phylogenetic tree of 390 kinesin motor
      domain sequences was built, grouping the Dictyostelium kinesins into nine
      subfamilies. According to known cellular functions or strong homologies to
      kinesins of other organisms, four of the Dictyostelium kinesins are involved in
      organelle transport, six are implicated in cell division processes, two are
      predicted to perform multiple functions, and one kinesin may be the founder of a
      new subclass. CONCLUSION: This analysis of the Dictyostelium genome led to the
      identification of eight new kinesin motor proteins. According to an exhaustive
      phylogenetic comparison, Dictyostelium contains the same subset of kinesins that
      higher eukaryotes need to perform mitosis. Some of the kinesins are implicated in
      intracellular traffic and a small number have unpredictable functions.

PMID- 14641910
TI  - Microarray analysis of tumor necrosis factor alpha induced gene expression in
      U373 human glioblastoma cells.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF) is able to induce a variety of
      biological responses in the nervous system including inflammation and
      neuroprotection. Human astrocytoma cells U373 have been widely used as a model
      for inflammatory cytokine actions in the nervous system. Here we used cDNA
      microarrays to analyze the time course of the transcriptional response from 1 h
      up to 12 h post TNF treatment in comparison to untreated U373 cells. TNF
      activated strongly the NF-kappaB transcriptional pathway and is linked to other
      pathways via the NF-kappaB target genes JUNB and IRF-1. Part of the TNF-induced
      gene expression could be inhibited by pharmacological inhibition of NF-kappaB
      with pyrrolidine-dithiocarbamate (PDTC). NF-kappaB comprises a family of
      transcription factors which are involved in the inducible expression of genes
      regulating neuronal survival, inflammatory response, cancer and innate immunity.
      RESULTS: In this study we show that numerous genes responded to TNF (> 880 from
      7500 tested) with a more than two-fold induction rate. Several novel TNF
      responsive genes (about 60% of the genes regulated by a factor > or = 3) were
      detected. A comparison of our TNF-induced gene expression profiles of U373, with
      profiles from 3T3 and Hela cells revealed a striking cell-type specificity. SCYA2
      (MCP-1, CCL2, MCAF) was induced in U373 cells in a sustained manner and at the
      highest level of all analyzed genes. MCP-1 protein expression, as monitored with
      immunofluorescence and ELISA, correlated exactly with microarray data. Based on
      these data and on evidence from literature we suggest a model for the potential
      neurodegenerative effect of NF-kappaB in astroglia: Activation of NF-kappaB via
      TNF results in a strongly increased production of MCP-1. This leads to a
      exacerbation of neurodegeneration in stoke or Multiple Sclerosis, presumably via
      infiltration of macrophages. CONCLUSIONS: The vast majority of genes regulated
      more than 3-fold were previously not linked to tumor necrosis factor alpha as a
      search in published literature revealed. Striking co-regulation for several
      functional groups such as proteasome and ribosomal proteins were detected.

PMID- 14641911
TI  - The molecular basis of lung cancer: molecular abnormalities and therapeutic
      implications.
AB  - Lung cancer is the number one cause of cancer-related death in the western world.
      Its incidence is highly correlated with cigarette smoking, and about 10% of long
      term smokers will eventually be diagnosed with lung cancer, underscoring the need
      for strengthened anti-tobacco policies. Among the 10% of patients who develop
      lung cancer without a smoking history, the environmental or inherited causes of
      lung cancer are usually unclear. There is no validated screening method for lung
      cancer even in high-risk populations and the overall five-year survival has not
      changed significantly in the last 20 years. However, major progress has been made
      in the understanding of the disease and we are beginning to see this knowledge
      translated into the clinic. In this review, we will summarize the current state
      of knowledge regarding the cascade of events associated with lung cancer
      development. From subclinical DNA damage to overt invasive disease, the
      mechanisms leading to clinically and molecularly heterogeneous tumors are being
      unraveled. These lesions allow cells to escape the normal regulation of cell
      division, apoptosis and invasion. While all subtypes of non-small cell lung
      cancer have historically been treated the same, stage-for-stage, recent
      technological advances have allowed a better understanding of the molecular
      classification of the disease and provide hypotheses for molecular early
      detection and targeted therapeutic strategies.

PMID- 14641912
TI  - Innate immune defences in the human endometrium.
AB  - The human endometrium is an important site of innate immune defence, giving
      protection against uterine infection. Such protection is critical to successful
      implantation and pregnancy. Infection is a major cause of preterm birth and can
      also cause infertility and ectopic pregnancy. Natural anti-microbial peptides are
      key mediators of the innate immune system. These peptides, between them, have
      anti-bacterial, anti-fungal and anti-viral activity and are expressed at
      epithelial surfaces throughout the female genital tract. Two families of natural
      anti-microbials, the defensins and the whey acidic protein (WAP) motif proteins,
      appear to be prominent in endometrium. The human endometrial epithelium expresses
      beta-defensins 1-4 and the WAP motif protein, secretory leukocyte protease
      inhibitor. Each beta-defensin has a different expression profile in relation to
      the stage of the menstrual cycle, providing potential protection throughout the
      cycle. Secretory leukocyte protease inhibitor is expressed during the secretory
      phase of the cycle and has a range of possible roles including anti-protease and
      anti-microbial activity as well as having effects on epithelial cell growth. The
      leukocyte populations in the endometrium are also a source of anti-microbial
      production. Neutrophils are a particularly rich source of alpha-defensins,
      lactoferrin, lysozyme and the WAP motif protein, elafin. The presence of
      neutrophils during menstruation will enhance anti-microbial protection at a time
      when the epithelial barrier is disrupted. Several other anti-microbials including
      the natural killer cell product, granulysin, are likely to have a role in
      endometrium. The sequential production of natural anti-microbial peptides by the
      endometrium throughout the menstrual cycle and at other sites in the female
      genital tract will offer protection from many pathogens, including those that are
      sexually transmitted.

PMID- 14641914
TI  - Health-related quality of life improves with treatment-related GERD symptom
      resolution after adjusting for baseline severity.
AB  - Severity and frequency of gastroesophageal reflux disease (GERD) related symptoms
      are associated with impaired health-related quality of life (HRQL). This study
      evaluated the association between baseline heartburn severity and endpoint HRQL
      of patients treated for heartburn and the relationship between complete
      resolution of heartburn symptoms and HRQL outcomes after controlling for baseline
      severity. We completed a secondary analysis of clinical symptom and HRQL data
      from three clinical trials in adult patients receiving either omeprazole or
      ranitidine treatment for GERD. HRQL was assessed using the Psychological General
      Well-Being Index (PGWB) in each of the three clinical trials, and two of the
      trials also included the Medical Outcomes Study Sleep disturbance scale.
      Gastrointestinal symptoms were evaluated using either the Gastrointestinal
      Symptom Rating Scale or a modified version of the scale. Baseline heartburn
      severity (none/minor, mild, moderate or severe) was defined based on patient
      reported symptoms. Analysis of covariance (ANCOVA) models were used to compare
      mean HRQL scores by baseline level of heartburn symptom severity and whether or
      not patients experienced complete heartburn resolution. At baseline, PGWB scores
      were significantly worse (p < 0.05) for patients with more severe heartburn
      symptoms. There were no statistically significant baseline severity by symptom
      resolution interactions in any of the ANCOVA models. For all three trials and
      across all follow-up assessments, mean PGWB scores were statistically
      significantly higher for patients with completely resolved heartburn symptoms
      versus those whose symptoms were unresolved (all p-values < 0.05). Few
      significant effects were observed for sleep disturbance scores. While the
      severity of heartburn symptoms at the start of medical treatment for GERD is not
      associated with improvements in HRQL in subsequent weeks of treatment, complete
      resolution of symptoms is associated with improvements in psychological well
      being.

PMID- 14641915
TI  - Cultural issues in using the SF-36 Health Survey in Asia: results from Taiwan.
AB  - BACKGROUND: The feasibility of using the SF-36 in non-Western cultures is
      important for researchers seeking to understand cultural influences upon health
      status perceptions. This paper reports on the performance of the Taiwan version
      of the SF-36, including the implications of cultural influences. METHODS: A total
      of 1191 volunteered subjects from the general population answered the translated
      SF-36 Taiwan version, which was developed following IQOLA project protocols.
      RESULTS: Results from tests of scaling assumptions and reliability generally were
      satisfactory. Convergent validity, as assessed by comparing the SF-36 to a mental
      health oriented inventory, was acceptable. Results of principal components
      analysis were similar to US results for many scales. However, differences were
      seen for the Vitality scale which was a stronger measure of mental health than
      physical health in Taiwan. Results are compared to those from other Asian studies
      and the U.S. CONCLUSION: The results raise important questions regarding cultural
      influences in international studies of health status assessment. Further research
      into the conceptualization and components of mental health in Asian countries is
      warranted.

PMID- 14641916
TI  - Generating neutralizing antibodies, Th1 response and MHC non restricted
      immunogenicity of HIV-I env and gag peptides in liposomes and ISCOMs with in
      built adjuvanticity.
AB  - For enhancing immunogenicity and develop vaccine strategies using peptide based
      constructs against HIV-1, a chimeric peptide containing V3 loop and transmembrane
      sequence of gp41 with two glycine motifs as spacer was constructed. The V3-gp41,
      gp41 peptide and p17 and p24 peptides separately or in a cocktail were entrapped
      with or without MA729 as an immunoadjuvant in liposomes or ISCOMs. The
      immunogenicity, antigen induced T-cell proliferation and cytokine profiles of
      various formulations were studied in four different inbred strains of mice of H
      2d, H-2b, H-2k and H-2q haplotypes, keeping alum as a control adjuvant. Both
      liposomes and ISCOM preparations elicited high titer and long lasting antibody
      response (60 days and above). When compared to the alum formulation, the
      liposomes co-entrapped with MA729 produced high antibody levels, comparable with
      that induced by ISCOMs. Peptide in alum, liposomes and ISCOMs enhanced both
      antigen specific IgG2a and IgG2b isotypes and high T-cell stimulation index.
      Peptide formulations also induced antibodies with high affinity and in vitro
      neutralizated the formation of HIV-1 syncytia. T-cell supernatants contained high
      levels of IFN-gamma and IL-2. Thus formulation in these adjuvants induced a
      predominant Th1 like response with MA729 as a versatile novel delivery vehicle
      for stimulating the appropriate arm of the immune response that can selectively
      modulate MHC class I or MHC class II response. The above peptide can be of wide
      vaccination interest as a means to improve immune responses to several other HIV
      1 antigens and may serve as candidates for vaccine development.

PMID- 14641917
TI  - The role of ATP and adenosine in the control of hepatic blood flow in the rabbit
      liver in vivo.
AB  - BACKGROUND: The role of adenosine and ATP in the regulation of hepatic arterial
      blood flow in the "buffer response" was studied in vitro and in a new in vivo
      model in the rabbit. The model achieves portal-systemic diversion by insertion of
      a silicone rubber prosthesis between the portal vein and inferior vena cava and
      avoids alterations in systemic haemodynamics. RESULTS: Hepatic arterial (HA)
      blood flow increased in response to reduced portal venous (PV) blood flow, the
      "buffer response", from 19.4 (3.3) ml min-1 100 g-1 to 25.6 (4.3) ml min-1 100 g
      1 (mean (SE), p < 0.05, Student's paired t-test). This represented a buffering
      capacity of 18.7 (5.2) %. Intra-portal injections of ATP or adenosine (1
      micrograms kg-1-0.5 mg kg-1) elicited immediate increases in HA blood flow to
      give -log ED50 values of 2.0 and 1.7 mg kg-1 for ATP and adenosine respectively.
      Injection of ATP and adenosine had no measurable effect on PV flow. In vitro,
      using an isolated dual-perfused rabbit liver preparation, the addition of 8
      phenyltheophylline (10 MicroMolar) to the HA and PV perfusate significantly
      inhibited the HA response to intra-arterial adenosine and to mid-range doses of
      intra-portal or intra-arterial ATP (p < 0.001). CONCLUSIONS: It is suggested that
      HA vasodilatation elicited by ATP may be partially mediated through activation of
      P1-purinoceptors following catabolism of ATP to adenosine.

PMID- 14641918
TI  - Analysis of CUL-5 expression in breast epithelial cells, breast cancer cell
      lines, normal tissues and tumor tissues.
AB  - BACKGROUND: The chromosomal location of CUL-5 (11q 22-23) is associated with LOH
      in breast cancer, suggesting that CUL-5 may be a tumor suppressor. The purpose of
      this research was to determine if there is differential expression of CUL-5 in
      breast epithelial cells versus breast cancer cell lines, and normal human tissues
      versus human tumors. The expression of CUL-5 in breast epithelial cells (HMEC,
      MCF-10A), and breast cancer cells (MCF-7, MDA-MB-231) was examined using RT-PCR,
      Northern blot analysis, and Western blot analysis. The expression of mRNA for
      other CUL family members (CUL-1, -2, -3, -4A, and -4B) in these cells was
      evaluated by RT-PCR. A normal human tissue expression array and a cancer
      profiling array were used to examine CUL-5 expression in normal human tissues and
      matched normal tissues versus tumor tissues, respectively. RESULTS: CUL-5 is
      expressed at the mRNA and protein levels by breast epithelial cells (HMEC, MCF
      10A) and breast cancer cells (MCF-7, MDA-MB-231). These cells also express mRNA
      for other CUL family members. The normal human tissue expression array revealed
      that CUL-5 is widely expressed. The cancer profiling array revealed that 82%
      (41/50) of the breast cancers demonstrated a decrease in CUL-5 expression versus
      the matched normal tissue. For the 50 cases of matched breast tissue there was a
      statistically significant approximately 2.2 fold decreased expression of CUL-5 in
      tumor tissue versus normal tissue (P < 0.0001). CONCLUSIONS: The data demonstrate
      no apparent decrease in CUL-5 expression in the breast cancer cell lines (MCF-7,
      MDA-MB-231) versus the breast epithelial cells (HMEC, MCF-10A). The decrease in
      CUL-5 expression in breast tumor tissue versus matched normal tissue supports the
      hypothesis that decreased expression of CUL-5 may play a role in breast
      tumorigenesis.

PMID- 14641920
TI  - Inadequate physician knowledge of the effects of diet on blood lipids and
      lipoproteins.
AB  - BACKGROUND: To assess the nutrition knowledge of physicians on the basic effects
      of diet on blood lipids and lipoproteins. METHODS: Anonymous mailed dietary
      knowledge surveys to 6000 randomly selected physicians in the United States
      licensed in either Internal Medicine or Cardiology. RESULTS: Response rate: 16%
      (n = 639). Half of the physicians did not know that canola oil and 26% did not
      know olive oil were good sources of monounsaturated fat. Ninety-three percent
      (84% of cardiologists vs. 96% of internists; p < 0.001) did not know that a low
      fat diet, in general, would increase blood triglycerides. Approximately three
      quarters (70% of cardiologists vs. 77% of internists; p < 0.01) did not know a
      low-fat diet would decrease HDL-c and almost half (45%) thought that a low-fat
      diet would not change HDL-c. CONCLUSIONS: If physicians are to implement dietary
      and cholesterol management guidelines, they will likely need to become more
      knowledgeable about nutrition.

PMID- 14641919
TI  - The relationship between wall shear stress distributions and intimal thickening
      in the human abdominal aorta.
AB  - PURPOSE: The goal of this work was to determine wall shear stress (WSS) patterns
      in the human abdominal aorta and to compare these patterns to measurements of
      intimal thickness (IT) from autopsy samples. METHODS: The WSS was experimentally
      measured using the laser photochromic dye tracer technique in an anatomically
      faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35
      year-old subject. IT was quantified as a function of circumferential and axial
      position using light microscopy in ten human autopsy specimens. RESULTS: The
      histomorphometric analysis suggests that IT increases with age and that the
      distribution of intimal thickening changes with age. The lowest WSS in the flow
      model was found on the posterior wall inferior to the inferior mesenteric artery,
      and coincided with the region of most prominent IT in the autopsy samples. Local
      geometrical features in the flow model, such as the expansion at the inferior
      mesenteric artery (common in younger individuals), strongly influenced WSS
      patterns. The WSS was found to correlate negatively with IT (r2 = 0.3099; P =
      0.0047). CONCLUSION: Low WSS in the abdominal aorta is co-localized with IT and
      may be related to atherogenesis. Also, rates of IT in the abdominal aorta are
      possibly influenced by age-related geometrical changes.

PMID- 14641921
TI  - Nutrition support to patients undergoing gastrointestinal surgery.
AB  - Nutritional depletion has been demonstrated to be a major determinant of the
      development of post-operative complications. Gastrointestinal surgery patients
      are at risk of nutritional depletion from inadequate nutritional intake, surgical
      stress and the subsequent increase in metabolic rate. Fears of postoperative
      ileus and the integrity of the newly constructed anastomosis have led to
      treatment typically entailing starvation with administration of intravenous
      fluids until the passage of flatus. However, it has since been shown that prompt
      postoperative enteral feeding is both effective and well tolerated. Enteral
      feeding is also associated with specific clinical benefits such as reduced
      incidence of postoperative infectious complications and an improved wound healing
      response. Further research is required to determine whether enteral nutrition is
      also associated with modulation of gut function. Studies have indicated that
      significant reductions in morbidity and mortality associated with perioperative
      Total Parenteral Nutrition (TPN) are limited to severely malnourished patients
      with gastrointestinal malignancy. Meta-analyses have shown that enteral nutrition
      is associated with fewer septic complications compared with parenteral feeding,
      reduced costs and a shorter hospital stay, so should be the preferred option
      whenever possible. Evidence to support pre-operative nutrition support is
      limited, but suggests that if malnourished individuals are adequately fed for at
      least 7-10 days preoperatively then surgical outcome can be improved. Ongoing
      research continues to explore the potential benefits of the action of glutamine
      on the gut and immune system for gastrointestinal surgery patients. To date it
      has been demonstrated that glutamine-enriched parenteral nutrition results in
      reduced length of stay and reduced costs in elective abdominal surgery patients.
      Further research is required to determine whether the routine supplementation of
      glutamine is warranted. A limitation for targeted nutritional support is the lack
      of a standardised, validated definition of nutritional depletion. This would
      enable nutrition support to be more readily targeted to those surgical patients
      most likely to derive significant clinical benefit in terms of improved post
      operative outcome.

PMID- 14641922
TI  - Vitamin A, carotenoid and vitamin E plasma concentrations in children from Laos
      in relation to sex and growth failure.
AB  - BACKGROUND: Deficiencies of vitamin A and its precursors, the carotenoids are
      common problems in developing countries. Plasma levels of these components are
      used as biomarkers of their availability. The study was conducted to evaluate
      whether blood plasma obtained from capillaries can be compared with plasma
      obtained from venous blood with regard to its levels of retinol, carotenoids and
      alpha-tocopherol and secondly to apply this technique to evaluate the levels of
      these components in children in a region with possible deficiencies. METHODS: The
      survey was conducted in a region of Laos in 81 children (age 35 to 59 months).
      Dietary intake was assessed by a questionnaire. Retinol, carotenoids and alpha
      tocopherol were determined by HPLC. Blood plasma was obtained either from
      capillary blood collected into microcapillaries and for reasons of methodological
      comparison in 14 adults from venous blood. RESULTS: The comparison between
      capillary and venous blood revealed that all components except zeaxanthin were 9
      23 % higher in plasma obtained from capillary blood. Results in Laotian children
      showed that all investigated components except retinol were significantly lower
      (P < 0.01) compared to European children of slightly older age. Contrary to
      children in Europe, most components were significantly lower in boys compared to
      girls. In children from Laos, lutein was the dominant carotenoid, while in
      children in Europe, beta-carotene was dominant. Within the Laotian children only
      a few differences were observed between stunted and non-stunted children and
      between children from lowland areas and high land areas. CONCLUSIONS: Results
      show that in consideration of slightly lower levels than in venous blood,
      capillary blood can be used to evaluate retinol, carotenoids and alpha-tocopherol
      as biomarkers of intake or status and to evaluate the possible effect of diet on
      absolute and relative carotenoid composition in children from Europe and Laos.
      Observed sex related differences might not be related to diet and would need
      further investigation.

PMID- 14641923
TI  - Trimetazidine improves left ventricular function in diabetic patients with
      coronary artery disease: a double-blind placebo-controlled study.
AB  - BACKGROUND: Patients with diabetic cardiomyopathy have an impaired myocardial
      glucose handling and distal distribution of coronary atherosclerosis.
      Trimetazidine, an anti-ischemic metabolic agent, improves myocardial glucose
      utilization though inhibition of fatty acid oxidation. Aim of the present study
      was to evaluate whether the metabolic effect of trimetazidine on left ventricular
      function in patients with diabetic cardiomyopathy. METHODS: 32 patients (24 males
      and 8 females, mean (SE) age = 67 +/- 6 years) with type 2 diabetes and ischemic
      cardiomyopathy were randomized to receive either trimetazidine (20 mg, t.d.s.) or
      placebo (t.d.s.) for six months in a randomized parallel study. Patients
      performed an echocardiogram at baseline and after 6 months. RESULTS: Demographic
      data were comparable between the two groups. After six month baseline left
      ventricular end-diastolic diameters increased from 62.4 +/- 1.7 to 63 +/- 2.1 mm
      in the placebo group, while decreased from 63.2 +/- 2.1 to 58 +/- 1.6 mm (p <
      0.01 compared to baseline) in the trimetazidine group. Compared to baseline, left
      ventricular ejection fraction increased by 5.4 +/- 0.5% (p < 0.05) in the
      trimetazidine group while remained unchanged in the placebo group -2.4 +/- 1.1%
      (NS), p < 0.01 between groups. A significant improvement in wall motion score
      index and in the E/A wave ratio was detected in patients treated with
      trimetazidine, but not in those receiving placebo. CONCLUSION: in diabetic
      patients with ischemic heart disease trimetazidine added to standard medical
      therapy has beneficial effect on left ventricular volumes and on left ventricular
      ejection fraction compared to placebo. This effect may be related to the effect
      of trimetazidine upon cardiac glucose utilization.

PMID- 14641924
TI  - A computer decision aid for medical prevention: a pilot qualitative study of the
      Personalized Estimate of Risks (EsPeR) system.
AB  - BACKGROUND: Many preventable diseases such as ischemic heart diseases and breast
      cancer prevail at a large scale in the general population. Computerized decision
      support systems are one of the solutions for improving the quality of prevention
      strategies. METHODS: The system called EsPeR (Personalized Estimate of Risks)
      combines calculation of several risks with computerisation of guidelines
      (cardiovascular prevention, screening for breast cancer, colorectal cancer,
      uterine cervix cancer, and prostate cancer, diagnosis of depression and suicide
      risk). We present a qualitative evaluation of its ergonomics, as well as it's
      understanding and acceptance by a group of general practitioners. We organised
      four focus groups each including 6-11 general practitioners. Physicians worked on
      several structured clinical scenarios with the help of EsPeR, and three senior
      investigators leaded structured discussion sessions. RESULTS: The initial
      sessions identified several ergonomic flaws of the system that were easily
      corrected. Both clinical scenarios and discussion sessions identified several
      problems related to the insufficient comprehension (expression of risks,
      definition of familial history of disease), and difficulty for the physicians to
      accept some of the recommendations. CONCLUSION: Educational, socio-professional
      and organisational components (i.e. time constraints for training and use of the
      EsPeR system during consultation) as well as acceptance of evidence-based
      decision-making should be taken into account before launching computerised
      decision support systems, or their application in randomised trials.

PMID- 14641925
TI  - The feasibility of using pattern recognition software to measure the influence of
      computer use on the consultation.
AB  - BACKGROUND: A key feature of a good general practice consultation is that it is
      patient-centred. A number of verbal and non-verbal behaviours have been
      identified as important to establish a good relationship with the patient.
      However, the use of the computer detracts the doctor's attention away from the
      patient, compromising these essential elements of the consultation. Current
      methods to assess the consultation and the influence of the computer on them are
      time consuming and subjective. If it were possible to measure these
      quantitatively, it could provide the basis for the first truly objective way of
      studying the influence of the computer on the consultation. The aim was to assess
      whether pattern recognition software could be used to measure the influence and
      pattern of computer use in the consultation. If this proved possible it would
      provide, for the first time, an objective quantitative measure of computer use
      and a measure of the attention and responsiveness of the general practitioner
      towards the patient. METHODS: A feasibility study using pattern recognition
      software to analyse a consultation was conducted. A web camera, linked to a data
      gathering node was used to film a simulated consultation in a standard office.
      Members of the research team enacted the role of the doctor and the patient,
      using pattern recognition software to try and capture patient-centred, non-verbal
      behaviour. As this was a feasibility study detailed results of the analysis are
      not presented. RESULTS: It was revealed that pattern recognition software could
      be used to analyse certain aspects of a simulated consultation. For example,
      trigger lines enabled the number of times the clinician's hand covered the
      keyboard to be counted and wrapping recorded the number of times the clinician
      nodded his head. It was also possible to measure time sequences and whether the
      movement was brief or lingering. CONCLUSION: Pattern recognition software enables
      movements associated with patient-centredness to be recorded. Pattern recognition
      software has the potential to provide an objective, quantitative measure of the
      influence of the computer on the consultation.

PMID- 14641926
TI  - Fistulotomy and drainage of deep postanal space abscess in the treatment of
      posterior horseshoe fistula.
AB  - BACKGROUND: Posterior horseshoe fistula with deep postanal space abscess is a
      complex disease. Most patients have a history of anorectal abscess drainage or
      surgery for fistula-in-ano. METHODS: Twenty-five patients who underwent surgery
      for posterior horseshoe fistula with deep postanal space abscess were analyzed
      retrospectively with respect to age, gender, previous surgery for fistula-in-ano,
      number of external openings, diagnostic studies, concordance between preoperative
      studies and operative findings for the extent of disease, operating time, healing
      time, complications, and recurrence. RESULTS: There were 22 (88%) men and 3 (12%)
      women with a median age of 37 (range, 25-58) years. The median duration of
      disease was 13 (range, 3-96) months. There was one external opening in 12 (48%)
      patients, 2 in 8 (32%), 3 in 4 (16%), and 4 in 1 (4%). Preoperative diagnosis of
      horseshoe fistula was made by contrast fistulography in 4 (16%) patients, by
      ultrasound in 3 (12%), by magnetic resonance imaging in 6 (24%), and by physical
      examination only in the remainder (48%). The mean +/- SD operating time was 47 +/
      10 min. The mean +/- SD healing time was 12 +/- 3 weeks. Three of the 25
      patients (12%) had diabetes mellitus type II. Nineteen (76%) patients had
      undergone previous surgery for fistula-in-ano, while five (20%) had only perianal
      abscess drainage. Neither morbidity nor mortality developed. All patients were
      followed up for a median of 35 (range, 6-78) months and no recurrence was
      observed. CONCLUSIONS: Fistulotomy of the tracts along the arms of horseshoe
      fistula and drainage of the deep postanal space abscess with posterior midline
      incision that severs both the lower edge of the internal sphincter and the
      subcutaneous external sphincter and divides the superficial external sphincter
      into halves gives excellent results with no recurrence. When it is necessary,
      severing the halves of the superficial external sphincter unilaterally or even
      bilaterally in the same session does not result in anal incontinence. Close
      follow-up of patients until the wounds completely healed is essential in the
      prevention of premature wound closure and recurrence.

PMID- 14641927
TI  - From evidence to best practice in the management of fractures of the distal
      radius in adults: working towards a research agenda.
AB  - BACKGROUND: Fracture of the distal radius is a common clinical problem,
      particularly in older white women with osteoporosis. We report our work towards
      evidence-based and patient-centred care for adults with these injuries. METHODS:
      We developed a systematic programme of research that built on our systematic
      review of the evidence of effectiveness of treatment interventions for these
      fractures. We devised schemata showing 'typical' care pathways and identified
      over 100 patient management questions. These depicted the more important
      decisions taken when progressing along each care pathway. We compiled a
      comprehensive document summarising the evidence available for each decision point
      from our reviews of randomised trials of treatment interventions. Using these
      documents, we undertook a formal and structured consultation process involving
      key players, including a patient representative, to obtain their views on the
      available evidence and to establish a research agenda. The resulting feedback was
      then processed and interpreted, using systematic methods. RESULTS: Some evidence
      from 114 randomised trials was available for 31 of the 117 patient management
      questions. However, there was sufficient evidence to base some conclusions of
      effectiveness for particular interventions in only five of these. Though only 60%
      of those approached responded, the responses received from the consultation group
      were often comprehensive and provided important insights into treatment practice
      and policy. There was a clear acceptance of the aims of the project and, aside
      from some suggestions for the more explicit inclusion of secondary prevention and
      management of complications, of the care pathways scheme. Though some respondents
      stressed that randomised trials were not always appropriate, there was no direct
      overall criticism of the evidence document and underlying processes. We were able
      to identify important core themes that underpin management decisions and research
      from the feedback of the consultation exercise. CONCLUSIONS: Overall, this
      project is an important advance towards evidence-based and patient-centred
      management of adults with distal radial fractures. It exposes the serious
      deficiency in the available evidence but also provides a template for further
      action. As well as being a valuable basis for viewing and informing current
      practice, the insights gained from this project should inform a future research
      agenda.

PMID- 14641928
TI  - Primary ciliary dyskinesia (Siewert's/Kartagener's syndrome): respiratory
      symptoms and psycho-social impact.
AB  - BACKGROUND: Although the pathophysiological defect in primary ciliary dyskinesia
      (PCD; Siewert's/Kartagener's syndrome) is now well characterised, there are few
      studies of the impact of the condition upon health function, particularly in
      later life. This study assesses the health impact of the condition in a large
      group of patients. In addition, it assesses the similarity in age of diagnosis,
      symptoms and problems of those with situs inversus (PCD-SI) and those with situs
      solitus (PCD-SS). METHODS: Postal questionnaire sent to members of the UK Primary
      Ciliary Dyskinesia Family Support Group. The questionnaire contained the St.
      George's Respiratory Questionnaire (SGRQ) and the SF-36 questionnaire for
      assessing health status. RESULTS: 93 questionnaires were returned, representing a
      66% response rate. Replies were received from similar numbers of PCD-SI and PCD
      SS. Individuals with PCD-SI did not show a significant tendency to be diagnosed
      earlier, and neither did they show any difference in their symptoms, or the
      relationship of symptoms to age. Respiratory symptoms were fairly constant up
      until the age of about 25, after which there was a slow increase in symptoms, and
      a decline in health status, patients over the age of 40 being about one and a
      half standard deviations below the mean on the physical component score of the
      PCS. Patients diagnosed earlier in life, and hence who had received more
      treatment for their condition, had better scores on the SGRQ Impact and Activity
      scores. CONCLUSIONS: PCD is a chronic condition which has a progressively greater
      impact on health in the second half of life, producing significant morbidity and
      restriction of life style. Early diagnosis, and hence earlier treatment, may
      improve symptoms and the impact of the condition.

PMID- 14641929
TI  - Household item ownership and self-rated health: material and psychosocial
      explanations.
AB  - BACKGROUND: There has been an ongoing debate whether the effects of socioeconomic
      factors on health are due to absolute poverty and material factors or to relative
      deprivation and psychosocial factors. In the present analyses, we examined the
      importance for health of material factors, which may have a direct effect on
      health, and of those that may affect health indirectly, through psychosocial
      mechanisms. METHODS: Random national samples of men and women in Hungary (n =
      973) and Poland (n = 1141) were interviewed (response rates 58% and 59%,
      respectively). The subjects reported their self-rated health, socioeconomic
      circumstances, including ownership of different household items, and perceived
      control over life. Household items were categorised as "basic needs", "socially
      oriented", and "luxury". We examined the association between the ownership of
      different groups of items and self-rated health. Since the lists of household
      items were different in Hungary and Poland, we conducted parallel identical
      analyses of the Hungarian and Polish data. RESULTS: The overall prevalence of
      poor or very poor health was 13% in Poland and 25% in Hungary. Education,
      material deprivation and the number of household items were all associated with
      poor health in bivariate analyses. All three groups of household items were
      positively related to self-rated health in age-adjusted analyses. The relation of
      basic needs items to poor health disappeared after controlling for other
      socioeconomic variables (mainly material deprivation). The relation of socially
      oriented and luxury items to poor health, however, persisted in multivariate
      models. The results were similar in both datasets. CONCLUSIONS: These data
      suggest that health is influenced by both material and psychosocial aspects of
      socioeconomic factors.

PMID- 14641930
TI  - High vitamin B12 level and good treatment outcome may be associated in major
      depressive disorder.
AB  - BACKGROUND: Despite of an increasing body of research the associations between
      vitamin B12 and folate levels and the treatment outcome in depressive disorders
      are still unsolved. We therefore conducted this naturalistic prospective follow
      up study. Our aim was to determine whether there were any associations between
      the vitamin B12 and folate level and the six-month treatment outcome in patients
      with major depressive disorder. Because vitamin B12 and folate deficiency may
      result in changes in haematological indices, including mean corpuscular volume,
      red blood cell count and hematocrit, we also examined whether these indices were
      associated with the treatment outcome. METHODS: Haematological indices,
      erythrocyte folate and serum vitamin B12 levels were determined in 115
      outpatients with DSM-III-R major depressive disorder at baseline and serum
      vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression
      Rating Scale was also compiled, respectively. In the statistical analysis we used
      chi-squared test, Pearson's correlation coefficient, the Student's t-test,
      analysis of variance (ANOVA), and univariate and multivariate linear regression
      analysis. RESULTS: Higher vitamin B12 levels significantly associated with a
      better outcome. The association between the folate level and treatment outcome
      was weak and probably not independent. No relationship was found between
      haematological indices and the six-month outcome. CONCLUSION: The vitamin B12
      level and the probability of recovery from major depression may be positively
      associated. Nevertheless, further studies are suggested to confirm this finding.

PMID- 14641931
TI  - X-linked hyper IgM (HIGM1) in an African kindred: the first report from South
      Africa.
AB  - BACKGROUND: The objective of this study was to describe the clinical and
      molecular features of the first South African family with X-linked hyper-IgM
      syndrome (HIGM1). METHODS: Diagnoses were based on immunoglobulin results and the
      absence of CD40 ligand (CD40L) expression on activated T-cells. Complete
      molecular characterisation involved CD40L cDNA sequencing, and genomic DNA
      analysis by polymerase chain reaction amplification, restriction enzyme digestion
      and sequencing. A PCR-based diagnostic assay was established for carrier
      detection and prenatal diagnosis in this family. RESULTS: There were originally
      six children, three males and three females. The eldest boy died after being
      diagnosed with hypogammaglobulinaemia, before HIGM1 was considered. This disorder
      was diagnosed in the second eldest boy at the age of 5 years, after failing to
      detect CD40L expression on his activated T-cells. A deficiency of CD40L was also
      confirmed in the youngest male at the age of 5 years. Both younger brothers have
      since died of infections relating to HIGM1. Molecular investigation showed that
      exon 3 was deleted from the CD40L mRNA of the affected males. Genomic DNA
      analysis identified a 1.5 kilobase deletion, spanning exon 3 and including
      extended flanking intronic sequence. Carrier status in the mother was confirmed
      by RT-PCR of her CD40L mRNA. Genetic analysis of the three female children was
      deferred because they were below the legal consenting age of 18 years. A PCR
      based assay for genomic DNA was established for easy identification of female
      carriers and affected males in the future. CONCLUSIONS: This study confirmed the
      diagnosis of HIGM1 in the first South African family to be investigated and
      identified a novel mutation in the CD40L gene.

PMID- 14641932
TI  - Previously unidentified changes in renal cell carcinoma gene expression
      identified by parametric analysis of microarray data.
AB  - BACKGROUND: Renal cell carcinoma is a common malignancy that often presents as a
      metastatic-disease for which there are no effective treatments. To gain insights
      into the mechanism of renal cell carcinogenesis, a number of genome-wide
      expression profiling studies have been performed. Surprisingly, there is very
      poor agreement among these studies as to which genes are differentially
      regulated. To better understand this lack of agreement we profiled renal cell
      tumor gene expression using genome-wide microarrays (45,000 probe sets) and
      compare our analysis to previous microarray studies. METHODS: We hybridized total
      RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix
      U133A and U133B arrays. We removed samples with technical defects and removed
      probesets that failed to exhibit sequence-specific hybridization in any of the
      samples. We detected differential gene expression in the resulting dataset with
      parametric methods and identified keywords that are overrepresented in the
      differentially expressed genes with the Fisher-exact test. RESULTS: We identify
      1,234 genes that are more than three-fold changed in renal tumors by t-test, 800
      of which have not been previously reported to be altered in renal cell tumors. Of
      the only 37 genes that have been identified as being differentially expressed in
      three or more of five previous microarray studies of renal tumor gene expression,
      our analysis finds 33 of these genes (89%). A key to the sensitivity and power of
      our analysis is filtering out defective samples and genes that are not reliably
      detected. CONCLUSIONS: The widespread use of sample-wise voting schemes for
      detecting differential expression that do not control for false positives likely
      account for the poor overlap among previous studies. Among the many genes we
      identified using parametric methods that were not previously reported as being
      differentially expressed in renal cell tumors are several oncogenes and tumor
      suppressor genes that likely play important roles in renal cell carcinogenesis.
      This highlights the need for rigorous statistical approaches in microarray
      studies.

PMID- 14641933
TI  - vCJD risk in the Republic of Ireland.
AB  - BACKGROUND: The Republic of Ireland has the second highest incidence of BSE
      worldwide. Only a single case of vCJD has been identified to date. METHODS: We
      estimate the total future number of clinical cases of vCJD using an established
      mathematical model, and based on infectivity of bovine tissue calculated from UK
      data and on the relative exposure to BSE contaminated meat. RESULTS: We estimate
      1 future clinical case (95% CI 0-15) of vCJD in the Republic of Ireland. Irish
      exposure is from BSE infected indigenous beef products and from imported UK beef
      products. Additionally, 2.5% of the Irish population was exposed to UK beef
      through residing in the UK during the 'at-risk' period. The relative proportion
      of risk attributable to each of these three exposures individually is 2:2:1
      respectively. CONCLUSIONS: The low numbers of future vCJD cases estimated in this
      study is reassuring for the Irish population and for other countries with a
      similar level of BSE exposure.

PMID- 14641934
TI  - A novel mutation of the calcium sensing receptor gene is associated with chronic
      pancreatitis in a family with heterozygous SPINK1 mutations.
AB  - BACKGROUND: The role of mutations in the serine protease inhibitor Kazal type 1
      (SPINK1) gene in chronic pancreatitis is still a matter of debate. Active SPINK1
      is thought to antagonize activated trypsin. Cases of SPINK1 mutations, especially
      N34S, have been reported in a subset of patients with idiopathic chronic
      pancreatitis. However, the inheritance pattern is still unknown. Some cases with
      N34S heterozygosity have been reported with and without evidence for CP
      indicating neither an autosomal recessive nor dominant trait. Therefore SPINK1
      mutations have been postulated to act as a disease modifier requiring additional
      mutations in a more complex genetic model. Familial hypocalciuric hypercalcemia
      (FHH) caused by heterozygous inactivating mutations in the calcium sensing
      receptor (CASR) gene is considered a benign disorder with elevated plasma calcium
      levels. Although hypercalcemia represents a risk factor for pancreatitis,
      increased rates of pancreatitis in patients with FHH have not been reported thus
      far. METHODS: We studied a family with a FHH-related hypercalcemia and chronic
      pancreatitis. DNA samples were analysed for mutations within the cationic
      trypsinogen (N29I, R122H) and SPINK1 (N34S) gene using melting curve analysis.
      Mutations within CASR gene were identified by DNA sequencing. RESULTS: A N34S
      SPINK1 mutation was found in all screened family members. However, only two
      family members developed chronic pancreatitis. These patients also had FHH caused
      by a novel, sporadic mutation in the CASR gene (518T>C) leading to an amino acid
      exchange (leucine->proline) in the extracellular domain of the CASR protein.
      CONCLUSION: Mutations in the calcium sensing receptor gene might represent a
      novel as yet unidentified predisposing factor which may lead to an increased
      susceptibility for chronic pancreatitis. Moreover, this family analysis supports
      the hypothesis that SPINK1 mutations act as disease modifier and suggests an even
      more complex genetic model in SPINK1 related chronic pancreatitis.

PMID- 14641935
TI  - Enhanced spontaneous activity of the mu opioid receptor by cysteine mutations:
      characterization of a tool for inverse agonist screening.
AB  - BACKGROUND: The concept of spontaneous- or constitutive-activity has become
      widely accepted and verified for numerous G protein-coupled receptors and this
      ligand-independent activity is also acknowledged to play a role in some
      pathologies. Constitutive activity has been reported for the mu opioid receptor.
      In some cases the increase in receptor basal activity was induced by chronic
      morphine administration suggesting that constitutive activity may contribute to
      the development of drug tolerance and dependence. Constitutively active mutants
      represent excellent tools for gathering information about the mechanisms of
      receptor activation and the possible physiological relevance of spontaneous
      receptor activity. The high basal level of activity of these mutants also allows
      for easier identification of inverse agonists, defined as ligands able to
      suppress spontaneous receptor activity, and leads to a better comprehension of
      their modulatory effects as well as possible in vivo use. RESULTS: Cysteines 348
      and 353 of the human mu opioid receptor (hMOR) were mutated into alanines and
      Ala348,353 hMOR was stably expressed in HEK 293 cells. [35S] GTPgammaS binding
      experiments revealed that Ala348,353 hMOR basal activity was significantly higher
      when compared to hMOR, suggesting that the mutant receptor is constitutively
      active. [35S] GTPgammaS binding was decreased by cyprodime or CTOP indicating
      that both ligands have inverse agonist properties. All tested agonists exhibited
      binding affinities higher for Ala348,353 hMOR than for hMOR, with the exception
      of endogenous opioid peptides. Antagonist affinity remained virtually unchanged
      except for CTOP and cyprodime that bound the double mutant with higher
      affinities. The agonists DAMGO and morphine showed enhanced potency for the
      Ala348,353 hMOR receptor in [35S] GTPgammaS experiments. Finally, pretreatment
      with the antagonists naloxone, cyprodime or CTOP significantly increased
      Ala348,353 hMOR expression. CONCLUSION: Taken together our data indicate that the
      double C348/353A mutation results in a constitutively active conformation of hMOR
      that is still activated by agonists. This is the first report of a stable CAM of
      hMOR with the potential to screen for inverse agonists.

PMID- 14641936
TI  - Measuring information integration.
AB  - BACKGROUND: To understand the functioning of distributed networks such as the
      brain, it is important to characterize their ability to integrate information.
      The paper considers a measure based on effective information, a quantity
      capturing all causal interactions that can occur between two parts of a system.
      RESULTS: The capacity to integrate information, or Phi, is given by the minimum
      amount of effective information that can be exchanged between two complementary
      parts of a subset. It is shown that this measure can be used to identify the
      subsets of a system that can integrate information, or complexes. The analysis is
      applied to idealized neural systems that differ in the organization of their
      connections. The results indicate that Phi is maximized by having each element
      develop a different connection pattern with the rest of the complex (functional
      specialization) while ensuring that a large amount of information can be
      exchanged across any bipartition of the network (functional integration).
      CONCLUSION: Based on this analysis, the connectional organization of certain
      neural architectures, such as the thalamocortical system, are well suited to
      information integration, while that of others, such as the cerebellum, are not,
      with significant functional consequences. The proposed analysis of information
      integration should be applicable to other systems and networks.

PMID- 14641937
TI  - Incorporation of gene-specific variability improves expression analysis using
      high-density DNA microarrays.
AB  - BACKGROUND: The assessment of data reproducibility is essential for application
      of microarray technology to exploration of biological pathways and disease
      states. Technical variability in data analysis largely depends on signal
      intensity. Within that context, the reproducibility of individual probe sets has
      not been hitherto addressed. RESULTS: We used an extraordinarily large replicate
      data set derived from human placental trophoblast to analyze probe-specific
      contribution to variability of gene expression. We found that signal variability,
      in addition to being signal-intensity dependant, is probe set-specific.
      Importantly, we developed a novel method to quantify the contribution of this
      probe set-specific variability. Furthermore, we devised a formula that
      incorporates a priori-computed, replicate-based information on probe set- and
      intensity-specific variability in determination of expression changes even
      without technical replicates. CONCLUSION: The strategy of incorporating probe set
      specific variability is superior to analysis based on arbitrary fold-change
      thresholds. We recommend its incorporation to any computation of gene expression
      changes using high-density DNA microarrays. A Java application implementing our T
      score is available at http://www.sadovsky.wustl.edu/tscore.html.

PMID- 14641938
TI  - Pyrosequencing trade mark : A one-step method for high resolution HLA typing.
AB  - While the use of high-resolution molecular typing in routine matching of human
      leukocyte antigens (HLA) is expected to improve unrelated donor selection and
      transplant outcome, the genetic complexity of HLA still makes the current
      methodology limited and laborious. Pyrosequencing trade mark is a gel-free,
      sequencing-by-synthesis method. In a Pyrosequencing reaction, nucleotide
      incorporation proceeds sequentially along each DNA template at a given nucleotide
      dispensation order (NDO) that is programmed into a pyrosequencer. Here we
      describe the design of a NDO that generates a pyrogram unique for any given
      allele or combination of alleles. We present examples of unique pyrograms
      generated from each of two heterozygous HLA templates, which would otherwise
      remain cis/trans ambiguous using standard sequencing based typing (SBT) method.
      In addition, we display representative data that demonstrate long read and linear
      signal generation. These features are prerequisite of high-resolution typing and
      automated data analysis. In conclusion Pyrosequencing is a one-step method for
      high resolution DNA typing.

PMID- 14641939
TI  - Integration of gene expression, clinical, and epidemiologic data to characterize
      Chronic Fatigue Syndrome.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or
      diagnostic laboratory abnormalities and it is unclear if it represents a single
      illness. The CFS research case definition recommends stratifying subjects by co
      morbid conditions, fatigue level and duration, or functional impairment. But to
      date, this analysis approach has not yielded any further insight into CFS
      pathogenesis. This study used the integration of peripheral blood gene expression
      results with epidemiologic and clinical data to determine whether CFS is a single
      or heterogeneous illness. RESULTS: CFS subjects were grouped by several clinical
      and epidemiological variables thought to be important in defining the illness.
      Statistical tests and cluster analysis were used to distinguish CFS subjects and
      identify differentially expressed genes. These genes were identified only when
      CFS subjects were grouped according to illness onset and the majority of genes
      were involved in pathways of purine and pyrimidine metabolism, glycolysis,
      oxidative phosphorylation, and glucose metabolism. CONCLUSION: These results
      provide a physiologic basis that suggests CFS is a heterogeneous illness. The
      differentially expressed genes imply fundamental metabolic perturbations that
      will be further investigated and illustrates the power of microarray technology
      for furthering our understanding CFS.

PMID- 14641940
TI  - Integrated strategies to tackle the inequitable distribution of doctors in
      Thailand: four decades of experience.
AB  - Inequitable distribution of doctors with high concentration in urban cities
      negatively affects the public health objective of Health for All. Thus it is one
      of the main concerns for most health policy makers, particularly in developing
      countries. This paper aims to summarize strategies to solve inequitable
      distribution of human resources for health (HRH) between urban and rural areas,
      by using four decades of experience in Thailand as a case study for analysis.

PMID- 14641941
TI  - Steroidal regulation of uterine resistance to bacterial infection in livestock.
AB  - Postpartum uterine infections reduce reproductive efficiency and have significant
      animal welfare and economic consequences. Postpartum uterine infections are
      classified as nonspecific, but Arcanobacterium pyogenes and Escherichia coli are
      usually associated with them in cattle and sheep. Pyometra is the most common
      type of uterine infection in dairy cattle, and it is detected almost exclusively
      in cows with active corpora lutea. Luteal progesterone typically down-regulates
      uterine immune functions and prevents the uterus from resisting infections.
      Progesterone also can down-regulate uterine eicosanoid synthesis. This seems to
      be a critical event in the onset of uterine infections, because eicosanoids can
      up-regulate immune cell functions in vitro. In addition, exogenous prostaglandin
      F2 alpha stimulates uterine secretion of prostaglandin F2 alpha and enhances
      immune functions in vivo. Thus, one may hypothesize that eicosanoids can override
      the negative effects of progesterone and that the up-regulatory effects of
      exogenous prostaglandin F2 alpha allow the uterus to resolve an infection,
      regardless of progesterone concentrations. Based on the results of studies to
      test that hypothesis, cows, sheep, and pigs in various physiological statuses are
      resistant to intrauterine infusions of Arcanobacterium pyogenes and Escherichia
      coli, unless progesterone concentrations are increased. In sheep and pigs,
      exogenous prostaglandin F2 alpha stimulates uterine production of prostaglandin
      F2 alpha and allows the uterus to resolve Arcanobacterium pyogenes-Escherichia
      coli-induced infections, even when progesterone is maintained at luteal phase
      concentrations before and after treatment. Prostaglandin F2 alpha is a
      proinflammatory molecule that stimulates the production of various
      proinflammatory cytokines, and it may enhance uterine production of leukotriene
      B4. Proinflammatory cytokines and leukotriene B4 enhance phagocytosis and
      lymphocyte functions. Even though there are clear associations among
      prostaglandin F2 alpha, leukotriene B4, proinflammatory cytokines, phagocytosis,
      and lymphocyte functions, the mechanism of action of exogenous prostaglandin F2
      alpha in overriding the down-regulatory effects of progesterone and resolving
      uterine infections has not been elucidated. Defining this mechanism should yield
      new prevention and treatment strategies for uterine infections that do not rely
      on antibiotic and antimicrobial compounds.

PMID- 14641942
TI  - Out of the box. Public health nutrition.

PMID- 14641943
TI  - Red palm oil as a source of vitamin A for mothers and children: impact of a pilot
      project in Burkina Faso.
AB  - OBJECTIVE: To demonstrate the effectiveness of the commercial introduction of red
      palm oil (RPO) as a source of vitamin A (VA) for mothers and children in a non
      consuming area, as a dietary diversification strategy. DESIGN: A pre-post
      intervention design (no control area) was used to assess changes in VA intake and
      status over a 24-month pilot project. SETTING AND SUBJECTS: The pilot project
      involved RPO promotion in 10 villages and an urban area in east-central Burkina
      Faso, targeting approximately 10 000 women and children aged <5 years. A random
      sample of 210 mother-child (12-36-months-old) pairs was selected in seven out of
      the 11 pilot sites for the evaluation. RESULTS: After 24 months, RPO was
      reportedly consumed by nearly 45% of mothers and children in the previous week.
      VA intake increased from 235+/-23 microg retinol activity equivalents (RAE) to
      655+/-144 microg RAE in mothers (41 to 120% of safe intake level), and from 164+/
      14 microg RAE to 514+/-77 microg RAE in children (36 to 97%). Rates of serum
      retinol <0.70 micromol l(-1) decreased from 61.8+/-8.0% to 28.2+/-11.0% in
      mothers, and from 84.5+/-6.4% to 66.9+/-11.2% in children. Those with a lower
      initial concentration of serum retinol showed a higher serum retinol response
      adjusted for VA intake. CONCLUSIONS: Commercial distribution of RPO was effective
      in reducing VA deficiency in the pilot sites. While it is promising as part of a
      national strategy, additional public health and food-based measures are needed to
      control VA malnutrition, which remained high in the RPO project area.

PMID- 14641944
TI  - Risk factors of obesity among Brazilian adolescents: a case-control study.
AB  - OBJECTIVE: To study risk factors associated with overweight and obesity among
      adolescents enrolled in private high schools in the city of Pelotas, southern
      Brazil. METHOD: This was a case-control study. The subjects were 264 overweight
      (body mass index (BMI) > or =85th percentile of the National Center for Health
      Statistics (NCHS) reference population) and 264 non-overweight (BMI >5th and
      <85th NCHS percentiles) adolescents identified by means of an anthropometric
      survey which included 1608 students. The adolescents were weighed, measured and
      interviewed about food habits and physical activity at school. Parents provided
      their own weights and heights when contacted by telephone, and parental BMI was
      calculated. RESULTS: Hierarchical multiple conditional logistic regression showed
      that overweight and obesity were positively associated with mother's (odds ratio
      (OR) 2.86, 95% confidence interval (Cl) 1.43-5.74) and father's (OR 2.43, 95% Cl
      1.37-4.30) BMI >/=30 kg m(-2), being overweight before 10 years of age (OR 2.26,
      95% Cl 1.30-3.90) and the habit of dieting (OR 3.53, 95% Cl 1.76-7.22). Having
      more than three meals per day was found to be a protective factor against
      overweight and obesity (OR 0.54, 95% Cl 0.29-1.00). CONCLUSION: The present study
      showed that a family history of obesity, overweight during childhood and the
      habit of dieting for weight-loss purposes are factors associated with obesity
      during adolescence. The habit of having more than three daily meals turned out to
      be a protective factor against overweight. These results suggest the necessity
      for early intervention at the family and general community levels aimed at the
      prevention of obesity through actions directed towards the modification of
      established behaviours.

PMID- 14641945
TI  - Sociodemographic variations in obesity among Ghanaian adults.
AB  - OBJECTIVES: To determine the sociodemographic associations of obesity in Ghana.
      DESIGN: A cross-sectional descriptive study was conducted on a sample of 6300
      adults aged 25 years and over who were selected by random cluster sampling.
      SETTING: Two urban (high-class and low-class suburbs) and a rural community in
      Accra, Ghana. SUBJECTS AND METHODS: In total, 4731 (1857 males, 2874 females)
      subjects participated. Demographic data were obtained by a questionnaire and
      height and weight were determined with subjects in light clothing and without
      shoes. RESULTS: The overall crude prevalence of overweight and obesity was 23.4
      and 14.1%, respectively. The rates of overweight (27.1 vs. 17.5%) and obesity
      (20.2 vs. 4.6%) were higher in females than males. Obesity increased with age up
      to 64 years. There were more overweight and obesity in the urban high-class
      residents compared with the low-class residents and in urban than rural subjects.
      Overweight and obesity were highest among the Akan and Ga tribes and relatively
      low among Ewes. Subjects with tertiary education had the highest prevalence of
      obesity (18.8%) compared with less literate and illiterate subjects (12.5-13.8%).
      Subjects whose jobs were of a sedentary nature had higher levels of obesity (15%)
      than subjects whose jobs involved heavy physical activity (10%). Subjects who did
      not engage in leisure-time physical activity were more obese than those who had
      three or more sessions of leisure-time physical activity per week (15.3 vs.
      13.5%). CONCLUSIONS: Overweight and obesity are common among residents in the
      Accra area. Older age, female gender, urban, high-class residence, sedentary
      occupation and tertiary education were associated with higher levels of obesity.
      Policies and programmes that promote healthy lifestyles may prove beneficial.

PMID- 14641946
TI  - Empowered women, social networks and the contribution of qualitative research:
      broadening our understanding of underlying causes for food and nutrition
      insecurity.
AB  - OBJECTIVE: To investigate underlying causes for food and nutrition insecurity in
      black South African households and to gain understanding of the factors
      contributing to better nutrition security, with emphasis on household
      organisation, gender and intra-household dynamics and social networks. DESIGN,
      SETTING AND SUBJECTS: Within a larger cross-sectional survey that investigated
      the impact of urbanisation on the health of black South Africans, 166 people,
      mostly women, were interviewed on household food security. Methods used were
      structured face-to-face interviews, in-depth interviews, observation, interviews
      with key informants and a sociodemographic questionnaire. Information was
      collected from 1998 to 2000 in 15 rural and urban areas of the North West
      Province, South Africa. RESULTS: Three-quarters of households in this sample are
      chronically food-insecure. Families are disrupted, due to migrant work, poverty
      and increasing societal violence, and half of households are female-headed.
      Certain categories of female-headed households and households based on
      partnership relationships, despite more limited resources, achieve a better or an
      equal economic status and better nutrition security than those households led by
      men, with the latter often being considered an economic liability. The reliance
      on and fostering of social ties and networks appear to be of central
      significance. CONCLUSION: Gender and intra-household relations, as well as social
      networks and income from informal sector activities, are often not uncovered by
      conventional statistical methods. Qualitative research can reveal the unexpected
      and furthermore empowers people, as their voices are heard.

PMID- 14641947
TI  - Evaluating the potential health gain of the World Health Organization's
      recommendation concerning vegetable and fruit consumption.
AB  - OBJECTIVE: The World Health Organization (WHO) recommends a daily intake of at
      least 400 g of vegetables and fruit. The aim of this paper was to evaluate the
      public health benefit of meeting this WHO recommendation by applying a
      statistical method that combines estimated intake distributions and simulated
      intake changes. DESIGN AND SETTING: The benefit of an increased consumption of
      vegetables and fruit was quantified by the preventable proportion of diseases.
      This proportion was estimated by a general formula derived in the paper that
      incorporates individual relative risks. Three different strategies of increasing
      usual intake were simulated and compared. The first strategy assumes that all
      individuals increase their intake by the same amount, the second assumes a
      constant increase among low consumers, and the third simulates individual
      increments necessary to meet the WHO recommendation. Calculations were made for
      three different scenarios with varying relative risks. RESULTS: The third
      simulation strategy turned out to be the most appropriate one to quantify the
      potential health gain of the current dietary recommendation. Applying this
      strategy to prevent cancer, the proportion of preventable cases was country
      specific. Estimates for France and Sweden were 21.9% and 19.3%, respectively,
      which are somewhat lower than the non-specific figure published by the World
      Cancer Research Fund. CONCLUSIONS: To improve estimates of the preventable
      proportion of diseases, the estimation formula presented here can be applied. Its
      application requires intake data to estimate the initial intake distribution in
      the population and to simulate adequate dietary changes.

PMID- 14641948
TI  - Social inequalities in infant feeding during the first year of life. The
      Longitudinal Study of Child Development in Quebec (LSCDQ 1998-2002).
AB  - OBJECTIVE: The aim of this paper is to describe the source and the scope of
      social inequalities in infant feeding practices. It examines the extent to which
      different recommendations are followed in different social groups and highlights
      the main factors influencing the total adherence to three recommendations at the
      population level. DESIGN, SETTING AND SUBJECTS: The study follows a
      representative sample (n=2103) of the children born in 1998 in the province of
      Quebec (Canada). Detailed information on breast-feeding and complementary feeding
      was collected at 5 and 17 months by face-to-face interviews with the mother. The
      independent variables were mother's age, mother's education level, poverty level,
      family type, socio-economic status (SES) and living area. Odds ratios (adjusted
      for baby's rank in the family, birth weight and premature birth) are presented
      for breast-feeding, and for formula and cows' milk consumption, at different
      ages. The adherence to a combined indicator cumulating three recommendations
      (breast-fed at birth, complementary food at 4 months or later and cows' milk at 9
      months or later) is also presented. RESULTS: The analysis indicates that
      adherence to the recommendations is low in Quebec. Breast-feeding initiation,
      duration and its exclusivity improved with mother's age and education level and
      SES. Adherence to the different recommendations was interrelated, indicating an
      accumulation of bad nutritional circumstances for children in low-SES families.
      The odds of being fed in accordance with the three studied recommendations, when
      living in a family with the highest SES, was 2.3 times higher than when living in
      a family with the lowest SES. When living with a highly educated mother, the odds
      ratio was 2.7 times higher than when living with a low-educated mother. For
      mother's age, the odds ratio reached 3.7 for children from mothers aged > or =35
      years, in comparison with children from mothers < or =24 years old. When SES or
      mother's education level was combined with mother's age, the children in the best
      situation were >8 more times likely than the least privileged children to be fed
      in accordance with these recommendations. Living area was not related with infant
      feeding during the first year of life. CONCLUSIONS: Breast-feeding and nutrition
      could be related with different health and cognitive outcomes in childhood and
      later in life. Consequently, social disparities in diet during infancy could play
      a role in the development of social and health inequalities more broadly observed
      at the population level. Intervention to improve adherence to breast-feeding and
      nutrition recommendations in infancy should be prioritised and evaluated for its
      impact on the reduction on infant diet inequalities over time.

PMID- 14641949
TI  - Iodine prophylaxis around the Semipalatinsk Nuclear Testing Site, Republic of
      Kazakstan.
AB  - OBJECTIVE: This study aimed to clarify the iodine deficiency status in the
      Semipalatinsk region that has been contaminated by radioactive fallout from
      nuclear testing during the period of the former USSR. DESIGN: Based on the Japan
      Kazakstan joint project of adult cancer screening around the Semipalatinsk
      Nuclear Testing Site (SNTS), from May to October 2002 spot urine specimens were
      collected at random in each village. Separately, children aged 5-15 years from
      around the SNTS were chosen at random and spot urine specimens were collected
      from them. SETTING: Area contaminated by radioactive fallout around the SNTS,
      Republic of Kazakstan. SUBJECTS: A total of 2609 adults aged >40 years from 16
      settlements in three regions and one city, and 298 children aged 5-15 years from
      two regions and one city. RESULTS: Median urinary iodine concentrations of adults
      and children in all regions were in the range of 116.0-381.7 and 127.7-183.0
      microg l(-1), respectively. The highest prevalence of values <50 microg l(-1)
      (14.1%) did not exceed 20%. Distributions within each group, adults and children,
      showed almost the same pattern, except for one region where more than 50% of
      adults had urinary iodine concentration >100 microg l(-1). CONCLUSIONS: In
      agreement with our previous studies, the urinary iodine concentration data showed
      no clear evidence of iodine deficiency around the SNTS. Kazakstan is
      geographically and nutritionally at moderate risk of iodine deficiency disorders
      without fortification or iodine replacement by iodised salt. The socio-medical
      prophylaxis against iodine deficiency has been successfully maintained in East
      Kazakstan.

PMID- 14641950
TI  - Food, alcohol and cigarette availability and consumption in Almaty, Kazakstan:
      results and appraisal of a rapid assessment.
AB  - OBJECTIVES: (1) To develop a useful tool to measure food, alcohol and tobacco
      items; (2) to document the availability of these items in Almaty, Kazakstan; (3)
      to describe the relationship between consumption and availability; and (4) to
      identify possible relationships between availability and health outcomes in the
      city and region. DESIGN: A survey of 648 vendors in Almaty, Kazakstan was
      conducted over one month from December 1999 to January 2000. Vendors identified
      which items they sold from a list of 61 food, alcohol and tobacco items. SETTING:
      Vendors were approached in three of the six regions of Almaty, Kazakstan. Regions
      canvassed included Auzov, one of the three 'sleeping regions'; Medeo, one of the
      two downtown regions; and Turksib, a more suburban/rural area of the city.
      RESULTS: There was a significant correlation between alcohol and cigarette
      consumption and availability. The relative availability of items was numerically
      and spatially consistent throughout the city. Fruits and vegetables occurred
      infrequently (<20% of sites) and in relative isolation from the rest of the
      system, while candy and cigarettes occurred with a higher relative frequency (75
      80% of sites). Maps of vendors showed clusters around geographical features such
      as major roads and intersections. CONCLUSIONS: Combining a checklist and mapping
      tools provides a model of consumer item availability that can help identify
      priorities for public health and urban planning professionals. The wide
      availability of cigarettes, alcohol, candy, coffee and tea, and limited
      availability of fruits, vegetables and whole grains, is likely to support
      increasing rates of chronic disease in Almaty.

PMID- 14641951
TI  - Lactose digestion in pregnant African-Americans.
AB  - OBJECTIVE: This paper reports on the status of lactose digestion during early and
      late pregnancy and at 8 weeks postpartum in an African-American population. The
      hypothesis is that lactose digestion and milk tolerance do not change throughout
      pregnancy and do not differ from those of non-pregnant African-American women.
      DESIGN AND SUBJECTS: This longitudinal study determined lactose digestion after
      ingesting 240 ml of 1% fat milk containing 12 g of lactose at: (1) early
      pregnancy, prior to 16 weeks (n=148); (2) late pregnancy, 30-35 weeks (n=77); and
      (3) 8 weeks postpartum (n=93). One hundred and one comparably matched non
      pregnant African-American women served as controls. RESULTS: Prevalence of
      lactose digestion, as measured by breath hydrogen, was 80.2% in the control
      women, 66.2% in early pregnancy, 68.8% in late pregnancy and 75.3% postpartum.
      The prevalence of women reporting symptoms was approximately 20% regardless of
      lactose absorption status. However, the control women reported significantly more
      symptoms than did the pregnant women. CONCLUSIONS: This study indicates that
      there is no significant change in lactose digestion during pregnancy. The
      prevalence of lactose intolerance for the pregnant African-American women studied
      is similar to that for non-pregnant African-American women and similar to
      previous prevalence reports in adult African-Americans. There was no change in
      the tolerance of lactose noted during pregnancy in these women. There were,
      however, fewer symptoms reported by the lactose-maldigesting pregnant women.

PMID- 14641952
TI  - Refined sugar intake in Australian children.
AB  - OBJECTIVE: To estimate the intake of refined sugar in Australian children and
      adolescents, aged 2-18 years. DESIGN: Foods contributing to total sugar intake
      were identified using data from the National Nutrition Survey 1995 (NNS95), the
      most recent national dietary survey of the Australian population. The top 100
      foods represented means of 85% (range 79-91%) and 82% (range 78-85%) of total
      sugar intake for boys and girls, respectively. Using published Australian food
      composition data (NUTTAB95), the proportion of total sugar being refined sugar
      was estimated for each food. Where published food composition data were not
      available, calculations from ingredients and manufacturer's information were
      used. SUBJECTS: The NNS95 assessed the dietary intake of a random sample of the
      Australian population, aged 2-18 years (n=3007). RESULTS: Mean daily intakes of
      refined sugar ranged from 26.9 to 78.3 g for 2-18-year-old girls, representing
      6.6-14.8% of total energy intake. Corresponding figures for boys were 27.0 to
      81.6 g and 8.0-14.0%, respectively. Of the 10 highest sources of refined sugar
      for each age group, sweetened beverages, especially cola-type beverages, were the
      most prominent. CONCLUSION: Refined sugar is an important contributor to dietary
      energy in Australian children. Sweetened beverages such as soft drinks and
      cordials were substantial sources of refined sugar and represent a potential
      target for campaigns to reduce refined sugar intake. Better access to information
      on the amounts of sugar added to processed food is essential for appropriate
      monitoring of this important energy source.

PMID- 14641953
TI  - Micronutrient intakes, micronutrient status and lipid profiles among young people
      consuming different amounts of breakfast cereals: further analysis of data from
      the National Diet and Nutrition Survey of Young People aged 4 to 18 years.
AB  - OBJECTIVE: To examine associations between breakfast cereal consumption and the
      dietary habits, nutrient intakes and nutritional status of young people,
      considering both nutrient adequacy and safety issues (fortification). METHODS:
      Using archived data from 1688 children in the (British) National Diet and
      Nutrition Survey of Young People aged 4 to 18 years, nutrient intakes and status
      were compared across thirds of breakfast cereal consumption (T1 to T3), adjusted
      for age and energy intake. Cereals provided on average 2%, 6% and 12% of energy
      in T1, T2 and T3, respectively, for boys; 1%, 4% and 10%, respectively, for
      girls. RESULTS: Intakes of iron, B vitamins and vitamin D were around 20-60%
      higher in T3 compared with T1, with significant linear relationships observed for
      iron, thiamin, riboflavin and folate (T1<T2<T3). After excluding low energy
      reporters and the unwell, 14% of girls had iron intakes below the Lower Reference
      Nutrient Intake and this varied fivefold between T1 and T3 (27%, 12% and 5%;
      P=0.0001). High consumers of breakfast cereals (T3) had better folate, vitamin
      B12 and riboflavin status and lower total and low-density lipoprotein
      cholesterol. There was also an association with thiamin and vitamin B6 status in
      girls. However, iron status (haemoglobin, ferritin and transferrin saturation)
      was not significantly different between groups, possibly due to lower meat
      intakes in T3. Total iron intakes were within tolerable levels (maximum of 32 mg
      day(-1) in one girl taking supplements). CONCLUSIONS: The nutritional benefits of
      breakfast cereals are demonstrated in status measurements as well as in nutrient
      intakes in this study. Concerns about excessive iron intakes from fortification
      appear unjustified.

PMID- 14641954
TI  - Reproducibility and validity of a food-frequency questionnaire for use among low
      income Brazilian workers.
AB  - OBJECTIVES: To assess the reproducibility and validity a 127-item, habitual
      intake, food-frequency questionnaire (FFQ), developed for low-income and low
      literacy Brazilian workers, by comparison with a 24-hour dietary recall (24-HDR).
      DESIGN: The FFQ and 24-HDR were interviewer-administered at the local workplace
      to each subject twice, with a period of 6 months between estimates; and four 24
      HDRs were conducted during the 4-month period between the two FFQs (FFQ1 and
      FFQ2). Reproducibility was tested by comparing mean nutrient intakes from the two
      FFQs. Validity was determined by comparing the mean nutrient intakes from the
      FFQs with the corresponding averages of the six 24-HDRs (reference method).
      SETTING: Goiania City, in Central West Brazil. SUBJECTS: The study was based on
      104 (62 women and 42 men) subjects, aged 18 to 60 years, who were randomly
      selected. RESULTS: Dietary intake from the FFQ was higher than from the 24-HDR.
      Reproducibility was assessed by Pearson correlation coefficients for nutrients
      from FFQ1 and FFQ2, and ranged from 0.23 for retinol to 0.69 for total energy
      (mean 0.52). Intra-class coefficients for nutrients averaged by the 24-HDRs
      ranged from 0.29 for vitamin C to 0.76 for total energy; retinol was not
      significant. In the validation study, correlation between the FFQ and the 24-HDR
      ranged between 0.21 for vitamin C and 0.70 for total energy (mean 0.50).
      Adjusting for total energy lowered the coefficients, except for calcium, retinol
      and vitamin C. Coefficients increased with attenuation, ranging from 0.35 for
      carbohydrate to 0.65 for calcium. CONCLUSIONS: Results indicate that this
      questionnaire had satisfactory reproducibility and reasonable validity.

PMID- 14641955
TI  - Quantitative approaches to nutrient density for public health nutrition.
AB  - Nutrient density, the vitamin or mineral content of a food or diet per unit
      energy, has long been a useful concept in the nutritional sciences. However, few
      nutritionists have applied the idea in quantitative, population-based nutrition
      planning and assessment. This paper discusses the conceptual issues related to
      the calculation of a nutrient density value that, if consumed, should meet the
      nutrient needs of most individuals in a population or sub-population, and
      outlines several methods for estimating this value. The paper also discusses the
      potential influence on the estimate's validity of factors such as skewed
      distributions and correlated energy intake and nutrient requirement.

PMID- 14641956
TI  - Competency development needs of the Australian public health nutrition workforce.
AB  - OBJECTIVES: To assess factors affecting competency development of the Australian
      public health nutrition workforce and investigate competency development
      intentions, barriers and self-reported training needs. DESIGN: Cross-sectional
      study using self-administered mail- or email-delivered questionnaire. SETTING AND
      SUBJECTS: Two hundred and forty practitioners working in designated community and
      public health nutrition positions in the Australian health system. RESULTS: An
      87% questionnaire response rate was achieved. The profile of the sample included
      female practitioners (95%) within the age range of 26-45 years (67%), from
      dietetic backgrounds (75%) and employed in state health departments as community
      dietitians/nutritionists (52%) or public health nutritionists (32%). Only 14% had
      completed higher degree qualifications but most (80%) reported an intention to do
      so in the future. Entry-level dietetic education was considered by most
      respondents (57%) to be inadequate preparation for public health nutrition
      practice but considered it had utility as a precursor for public health nutrition
      competency development because of its strong grounding in nutrition knowledge,
      basic research skills and problem-solving. On-the-job learning was the most
      prominent competency development influence reported by this workforce.
      Flexibility in teaching and learning approaches is needed to facilitate workforce
      participation in further competency development. The main competency development
      needs focused on analytical and policy process competencies; however, there was a
      general need expressed for competency development across many competency areas.
      CONCLUSIONS: These data provide intelligence to inform public health nutrition
      workforce development, particularly that relating to continued professional
      development amongst the existing workforce.

PMID- 14641958
TI  - Does breakfast-club attendance affect schoolchildren's nutrient intake? A study
      of dietary intake at three schools.
AB  - Lack of breakfast has been implicated as a factor contributing to children's poor
      diets and school performance. Breakfast-club schemes, where children are provided
      with breakfast in school at the start of the school day, have been initiated by
      the Department of Health in schools throughout England, UK. The aim of the
      present study was to compare the energy and nutrient intakes of schoolchildren
      who attended breakfast clubs (attendee subjects) with those who did not (control
      subjects). Three different schools were studied, involving a total of 111
      children aged between 9 and 15 years. There were fifty-nine attendee and fifty
      two control subjects. The two groups were matched for eligibility for school
      meals. All subjects completed a 3 d weighed food diary for estimation of nutrient
      intake. Height and weight were measured and BMI calculated. Nutrient intake data
      were analysed using a general linear model with age as a covariate. The
      demographic and anthropometric characteristics of the attendee and control
      subjects were similar. Children who attended breakfast clubs had significantly
      greater intakes of fat (% energy), saturated fat (% energy) and Na than control
      subjects. Thus, in these schools breakfast-club participation was not associated
      with superior nutrient intake or improvements in dietary pattern.

PMID- 14641959
TI  - Prebiotics affect nutrient digestibility but not faecal ammonia in dogs fed
      increased dietary protein levels.
AB  - An increased protein content and less digestible protein sources in the diet can
      induce bad faecal odour. The present study investigated the effect of adding
      prebiotics to dog diets enriched with animal-derived protein sources on apparent
      digestibilities and faecal ammonia concentration. In three subsequent periods
      eight healthy beagle dogs were fed a commercial dog diet that was gradually
      supplemented by up to 50 % with meat and bone meal (MBM), greaves meal (GM) or
      poultry meal (PM) respectively. Afterwards, 3 % fructo-oligosaccharides or 3 %
      isomalto-oligosaccharides were substituted for 3 % of the total diet.
      Supplementation with animal-derived protein sources did not decrease the apparent
      N digestibility significantly but oligosaccharides did. On the other hand the
      bacterial N content (% DM) in the faeces was highest in the oligosaccharide
      groups followed by the protein-supplemented groups and lowest in the control
      groups. When the apparent N digestibility was corrected for bacterial N no
      significant differences were noted anymore except for the GM group where the
      corrected N digestibility was still lower after oligosaccharide supplementation.
      The amount of faecal ammonia was significantly increased by supplementing with
      protein or oligosaccharides in the MBM and GM groups but not in the PM group.
      When apparent N digestibility is interpreted, a correction for bacterial N should
      be taken into account, especially when prebiotics are added to the diet.
      Oligosaccharides did not reduce the faecal ammonia concentrations as expected.

PMID- 14641960
TI  - Monounsaturated n-9 fatty acids and adipocyte lipolysis in rats.
AB  - To investigate the role of the monounsaturated n-9 fatty acids (MUFA) in the
      lipolytic activity of adipocytes, a study was carried out in which an increase in
      MUFA was produced in the tissues by two different methods; by the dietary
      enrichment of oleic acid or by producing an essential fatty acid deficiency
      syndrome. For this, forty-five male Sprague-Dawley rats were fed with a normal
      energy diet and were subdivided into three groups. The diets varied in the type
      of dietary fat; palmitic acid, olive oil, or soyabean oil+palmitic acid. At the
      end of the study measurements were taken of weight, plasma leptin, tissue
      concentration of fatty acids, fat-cell size in the epididymal and the omental
      adipose tissues, adipocyte lipolytic activity of both tissues after stimulation
      with adrenaline, and the capacity of insulin to inhibit lipolysis. The baseline
      and adrenaline-stimulated lipolytic activity were greater and the anti-lipolytic
      capacity of insulin lower in the animals undergoing an increase in MUFA in the
      tissues (palmitic-acid and olive-oil diets). The area under the curve of
      glycerol, used as an indicator of lipolytic activity, was positively correlated
      with the concentration of MUFA and negatively with polyunsaturated fatty acids in
      the adipose tissues. It is concluded that an increase in tissue MUFA, however
      obtained, induces an increase in lipolytic activity.

PMID- 14641961
TI  - Early post-hatching starvation delays p70 S6 kinase activation in the muscle of
      neonatal chicks.
AB  - Chicken muscle ribosomal protein S6 kinase (S6K1) has been recently characterised
      and its enzymic activity is regulated by the nutritional and hormonal (insulin)
      status in vivo. The regulation of S6K1 is still unknown in neonatal chicks. The
      present study aimed to compare the activation of S6K1 in early-feeding (EF) and
      48 h-delayed-feeding (DF) chicks from hatching to 4 d of age. During post
      hatching starvation, S6K1 activity remained at the basal level measured in the
      control-hatched chicks. The maximum S6K1 activity was recorded on the first day
      of feeding with an increase of about 2.5-fold in the EF and DF chicks (P<0.01).
      S6K1 activity was correlated with plasma insulin level, suggesting a probable
      insulin-dependent S6K1 activation. The feeding-induced increase in S6K1 activity
      was related to its Thr389 residue phosphorylation. A similar pattern for protein
      kinase B phosphorylation was observed, upstream from S6K1. The S6K1 pathway was
      stimulated to the same extent in the EF and DF chicks, which indicates that post
      hatching starvation did not increase S6K1 activation. It is concluded that muscle
      S6K1 is activated as soon as food is available without improvement in the
      response of the S6K1 pathway after post-hatching starvation.

PMID- 14641962
TI  - Tomatoes have natural anti-thrombotic effects.
AB  - The prevention of arterial thrombotic diseases has a high priority in developed
      countries. An inappropriate diet may be an important risk factor for thrombotic
      events. The daily intake of an anti-thrombotic diet may offer a convenient and
      effective way of prevention. The aim of the present study was to test tomato
      extracts for anti-thrombotic effects and to identify those varieties that have
      such an effect. A shear-induced platelet-function test (haemostatometry) was used
      to test anti-thrombotic potential in vitro. Extracts from those tomato varieties
      that showed a significant anti-thrombotic activity in vitro were further assessed
      in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99
      4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4
      inhibited not only platelet-rich thrombus formation but also had a thrombolytic
      effect. It is concluded that haemostatometry can detect and classify the anti
      thrombotic potential of fruits and vegetables and offers a simple way of
      screening for such effects.

PMID- 14641963
TI  - Effects of dietary cis 9, trans 11-18:2, trans 10, cis 12-18:2, or vaccenic acid
      (trans 11-18:1) during lactation on body composition, tissue fatty acid profiles,
      and litter growth in mice.
AB  - Cis 9, trans 11 (c 9, t11)-18:2 and trans 10, cis 12 (t10, c12)-18:2 are the
      major conjugated linoleic acid (CLA) isomers in dietary supplements which reduce
      milk fat content in nursing women. The present study evaluated the effects of
      each CLA isomer or vaccenic acid on body composition and tissue fatty acids
      during lactation in mice. Dams were fed 30 g rapeseed oil (control)/kg diet or 20
      g control plus 10 g 18:0, trans 11-18:1 (t11-18:1), c 9, t11-18:2, or t10, c12
      18:2. Dietary t10, c12-18:2 reduced food intake by 18 % and carcass fat weight of
      the dams by 49 % compared with the other treatments. Milk fat percentage ranked
      by treatment was 18:0>t11-18:1=c 9, t11-18:2>t10, c12-18:2. The sum of saturated
      12:0 to 16:0 in milk fat was lower when c 9, t11-18:2 was fed compared with the
      control, 18:0, or t11-18:1 treatments. Dietary t10, c12-18:2 caused further
      reductions in milk fat 12:0 to 16:0. The proportion of CLA isomers was 3-fold
      greater in milk fat than in the carcasses of the dams. The pups nursing from the
      dams fed t10, c12-18:2 had the lowest body weights and carcass fat, protein, and
      ash contents. Nursing from the dams fed c 9, t11-18:2 also resulted in lower
      carcass fat compared with the 18:0 or t11-18:1 treatments. The ratios of cis 9
      16:1:16:0 or cis 9-18:1:18:0, proxies for Delta(9)-desaturase activity, were
      markedly lower in the carcasses of the dams and pups fed t10, c12-18:2. The ratio
      of 20:4n-6:18 : 2n-6, a proxy for Delta(6)- and Delta(5)-desaturase and elongase
      activity, in the liver of the dams and pups fed t10, c12-18:2 also was lower.
      Dietary t11-18:1 enhanced the content of c 9, t11-18:2 in milk fat and carcasses.
      As in previous studies, the reduction in food intake by t10, c12-18:2 could not
      entirely account for the marked decrease in carcass fat content and milk fat
      concentration. T10, c12-18:2 probably had a negative effect on Delta(9)
      desaturase and mammary de novo fatty acid synthesis. Although these effects need
      to be confirmed in lactating women, the results suggest that the consumption of
      supplements containing t10, c12-18:2 should be avoided during the nursing period.

PMID- 14641964
TI  - The influence of high-carbohydrate meals with different glycaemic indices on
      substrate utilisation during subsequent exercise.
AB  - The present study was designed to examine the effects of mixed high-carbohydrate
      meals with different glycaemic indices (GI) on substrate utilization during
      subsequent exercise. Nine healthy male recreational runners (age 26.8 (sem 1.1)
      years, body mass 74.7 (sem 2.4) kg, VO2max 58.1 (sem 1.7) ml/kg per min)
      completed three trials: high-glycaemic-index meal (HGI), low-glycaemic-index meal
      (LGI) and fasting (FAST), separated by 7 d. The test meals contained 2 g
      carbohydrate/kg body mass, they were isoenergetic and the GI values were 77.4,
      36.9 and 0.0 respectively. In each trial, subjects consumed the test meal 3 h
      before performing a 60 min run at 65 % VO2max on a motorized treadmill. Ingestion
      of the HGI and LGI resulted in hyperglycaemia and hyperinsulinaemia during the
      postprandial period compared with the FAST (P<0.05). The incremental area under
      the curve for plasma glucose was 2-fold higher for HGI compared with LGI (108.7
      v. 48.9 mmol/l per min). In contrast, plasma non-esterified fatty acid
      concentrations were significantly lower following HGI and LGI compared with FAST
      (P<0.05). During the subsequent submaximal exercise, plasma glucose declined to
      below the fasting value in HGI compared with LGI and FAST (P<0.05). The estimated
      total fat oxidation was significantly higher for the LGI than the HGI during
      exercise (P<0.05). In summary, both pre-exercise carbohydrate meals resulted in
      lower rates of fat oxidation during subsequent exercise than when subjects
      performed exercise in the fasting state. However, the LGI resulted in a higher
      rate of fat oxidation during exercise than following the consumption of the HGI.

PMID- 14641965
TI  - Butyrate is only one of several growth inhibitors produced during gut flora
      mediated fermentation of dietary fibre sources.
AB  - Dietary fibre sources are fermented by the gut flora to yield short-chain fatty
      acids (SCFA) together with degraded phytochemicals and plant nutrients. Butyrate,
      a major SCFA, is potentially chemoprotective by suppressing the growth of tumour
      cells and enhancing their differentiation. Conversely, it could lead to a
      positive selection pressure for transformed cells by inducing glutathione S
      transferases (GST) and enhancing chemoresistance. Virtually nothing is known
      about how butyrate's activities are affected by other fermentation products. To
      investigate such interactions, a variety of dietary fibre sources was fermented
      with human faecal slurries in vitro, analysed for SCFA, and corresponding SCFA
      mixtures were prepared. HT29 colon tumour cells were treated for 72 h with
      individual SCFA or complex samples. The growth of cells, GST activity, and
      chemoresistance towards 4-hydroxynonenal were determined. Fermentation products
      inhibited cell growth more than the corresponding SCFA mixtures, and the SCFA
      mixtures were more active than butyrate, probably due to phytoprotectants and to
      propionate, respectively, which also inhibit cell growth. Only butyrate induced
      GST, whereas chemoresistance was caused by selected SCFA mixtures, but not by all
      corresponding fermentation samples. In summary, fermentation supernatant
      fractions contain compounds that: (1) enhance the anti-proliferative properties
      of butyrate (propionate, phytochemical fraction); (2) do not alter its capacity
      to induce GST; (3) prevent chemoresistance in tumour cells. It can be concluded
      that fermented dietary fibre sources are more potent inhibitors of tumour cell
      growth than butyrate alone, and also contain ingredients which counteract the
      undesired positive selection pressures that higher concentrations of butyrate
      induce in tumour cells.

PMID- 14641966
TI  - The effect of feeding structured triacylglycerols enriched in eicosapentaenoic or
      docosahexaenoic acids on murine splenocyte fatty acid composition and leucocyte
      phagocytosis.
AB  - The effects of altering the type of n-3 polyunsaturated fatty acid (PUFA) in the
      mouse diet on the ability of monocytes and neutrophils to perform phagocytosis
      were investigated. Male weanling mice were fed for 7 d on one of nine diets which
      contained 178 g lipid/kg and which differed in the type of n-3 PUFA and in the
      position of these in dietary triacylglycerol (TAG). The control diet contained
      4.4 g alpha-linolenic acid/100 g total fatty acids. In the other diets,
      eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) replaced a proportion
      (50 or 100 %) of the alpha-linolenic acid, and were in the sn-2 or the sn-1(3)
      position of dietary TAG. There were significant increases in the content of n-3
      PUFA in spleen-cell phospholipids when EPA or DHA was fed. These increases were
      largely independent of the position of EPA or DHA in dietary TAG except when EPA
      was fed at the highest level, when the incorporation was greater when it was fed
      in the sn-2 than in the sn-1(3) position. There was no significant effect of
      dietary DHA on monocyte or neutrophil phagocytic activity. Dietary EPA dose
      dependently decreased the number of monocytes and neutrophils performing
      phagocytosis. However, when EPA was fed in the sn-2 position, the ability of
      active monocytes or neutrophils to engulf bacteria was increased in a dose
      dependent fashion. This did not occur when EPA was fed in the sn-1(3) position.
      Thus, there appears to be an influence of the position of EPA, but not of DHA, in
      dietary TAG on its incorporation into cell phospholipids and on the activity of
      phagocytic cells.

PMID- 14641967
TI  - Iron absorption from ferrous fumarate in adult women is influenced by ascorbic
      acid but not by Na2EDTA.
AB  - Ascorbic acid and Na2EDTA enhance Fe absorption from the water-soluble Fe
      compound FeSO4 but their effect on poorly water-soluble Fe compounds such as
      ferrous fumarate is less well established. In the present study, the effects of
      ascorbic acid and Na2EDTA on Fe absorption from ferrous fumarate were evaluated
      in adult women (ten women/study) from the erythrocyte incorporation of Fe stable
      isotopes ((57)Fe or (58)Fe) 14 d after administration. Two separate studies were
      made with test meals of Fe-fortified infant cereal (5 mg Fe/meal). Data were
      evaluated by paired t tests and the results are presented as geometric means. In
      study 1a, the comparison between Fe absorption from ferrous fumarate- and FeSO4
      fortified cereal showed that adult women absorb Fe as well from ferrous fumarate
      as from FeSO4 (3.0 and 3.1 % respectively, P=0.85). After addition of Na2EDTA
      (Na2EDTA:fortification Fe molar ratio of 1:1), Fe absorption from FeSO4 was
      significantly higher than from ferrous fumarate (5.3 v. 3.3 % respectively,
      P<0.01; study 1b). In study 2, Fe absorption was compared from ferrous fumarate
      fortified meals with and without ascorbic acid added at a 4:1 molar ratio
      (relative to fortification Fe) and the results showed that ascorbic acid
      increased Fe absorption from ferrous fumarate significantly (6.3 v. 10.4 %,
      P=0.02). The results of the present studies show that Fe absorption from ferrous
      fumarate is enhanced by ascorbic acid but not by Na2EDTA, thus emphasising that
      not all findings from Fe absorption studies made with FeSO4 can be extrapolated
      to Fe compounds with different solubility properties.

PMID- 14641968
TI  - Number of days, number of subjects, and sources of variation in longitudinal
      intervention or crossover feeding trials with multiple days of measurement.
AB  - Dietary studies are often conducted as longitudinal intervention or crossover
      trials using multiple days of measurement on each subject during each of several
      measurement periods, and determining the required numbers of days and subjects is
      important in designing these studies. Linear mixed statistical models were used
      to derive equations for precision, statistical power and sample size (number of
      days and number of subjects) and to obtain estimates of between-subject, period
      to-period, and day-to-day variation needed to apply the equations. Two cohorts of
      an on-going exercise intervention study, and a crossover study of Olestra, each
      with 14 d of measurement/subject per period, were used to obtain estimates of
      variability for energy and macronutrient intake. Numerical examples illustrate
      how the equations for calculating the number of days or number of subjects are
      applied in typical situations, and sample SAS code is given. It was found that
      between-subject, period-to-period, and day-to-day variation all contributed
      significantly to the variation in energy and macronutrient intake. The ratio of
      period-to-period and day-to-day standard deviations controls the trade-off
      between the number of days and the number of subjects, and this remained
      relatively stable across studies and energy and macronutrient intake variables.
      The greatest gains in precision were seen over the first few measurement days.
      Greater precision and fewer required days were noted in the study (Olestra) that
      exerted greater control over the subjects and diets during the feeding protocol.

PMID- 14641969
TI  - Feeding difficulties in disabled children leads to malnutrition: experience in an
      Indian slum.
AB  - The aim of the present study was to explore the nature, extent and probable
      causes of nutritional deficiencies among children with disabilities living in
      Dharavi, a slum in Mumbai, India. A cross-sectional study was conducted to
      investigate whether the nutritional status of children with disabilities, aged 2
      6 years (n 141), was worse than that of non-disabled sibling controls (n 122) and
      neighbour controls (n 162). Data on food patterns, anthropometry, micronutrient
      status and feeding difficulties reported by parents were collected. The mean
      weight for age of the children with disabilities (-2.44 (SD 1.39) Z scores; n
      120) was significantly lower (P<0.05) compared with the sibling (-1.70 (SD 1.20)
      Z scores; n 109) and neighbour (-1.83 (SD 1.290) Z scores; n 162) control groups.
      The children with disabilities had significantly lower (P<0.05) mean haemoglobin
      levels (92 (SD 23) g/l; n 134) compared with siblings (102 (SD 18) g/l; n 103)
      and neighbours (99 (SD 18) g/l; n 153). Relative risk (RR) analysis indicated
      that the disabled children with feeding difficulties were significantly more
      likely (P<0.05) to be malnourished, by the indicator of weight for age (RR 1.1;
      95 % CI 1.08, 1.20) compared with the disabled children without a feeding
      difficulty. They were also significantly more likely to be malnourished using the
      indicators of height for age (RR 1.3; 95 % CI 1.19, 1.43) and weight for height
      (RR 2.4; 95 % CI 1.78, 3.23) compared with the disabled children without a
      feeding difficulty. Feeding difficulties were identified as a risk factor for
      vulnerability to inadequate nutritional status among children with disabilities.

PMID- 14641970
TI  - Daily protein intakes and eating patterns in young and elderly French.
AB  - An adequate level of protein intake is required to limit the gradual body protein
      loss observed during ageing. Different factors (cohort age, sex, life conditions)
      may modify protein intake and distribution. However the precise amounts, as well
      as their daily distribution which affects protein utilisation and N retention,
      are unknown in both young and elderly individuals. The hypothesis was tested that
      protein intake and its distribution over daily meals could be different between
      the young and elderly. The consumption of six different protein-rich food groups
      by 292 healthy individuals aged 20-30 and 65-75 years was determined throughout
      each day for 1 week. The data of the total protein intake and protein intakes at
      each meal were analysed by ANOVA for each sex separately, using age group as the
      independent factor. The average protein intake of men was lower in the older age
      group whilst the opposite trend was seen in women. The distribution of protein
      intake was different between the two age groups: 56.5 % of the daily protein was
      eaten at lunch by the elderly but only 47 % (P<0.0001) by the younger subjects.
      In the elderly subjects, those eating larger amounts consumed a greater
      proportion of protein-rich foods at dinner than those eating small amounts (30.4
      v. 26.2 %, P=0.05). A high level of protein intake was related to a higher meat
      product consumption in both the elderly and young individuals. In conclusion, the
      pattern of protein intake differs significantly between age groups and sexes.

PMID- 14641971
TI  - Total-diet study: dietary intakes of macro elements and trace elements in Italy.
AB  - The present study provides the dietary intakes of macro elements (Ca, Mg, Na, K,
      P) and trace elements (Fe, Zn, Cu, Se) from the Italian total diet. The
      contribution of the most representative food groups of the total diet (cereals
      and cereal products, vegetables, fruit, milk and dairy products, meat and meat
      products, fish) to the daily intakes of these nutrients was also evaluated. The
      Italian total diet was formulated following the 'market-basket' approach. Cereals
      represented the primary sources of Cu (35 %), Fe (30 %) and Mg (27 %). About 89 %
      of the total daily intake of Fe was derived from plant foods. The vegetables food
      group was the main source of dietary K (27 %). Most of the Ca (59 %) and P (27 %)
      was derived from the milk-and-dairy food group. Of the dietary Zn, 41 % was
      provided by meat, which, together with the fish food group, was the primary
      source of Se (20 %). The adequacy of the Italian total diet with respect to
      nutritional elements was assessed by comparing the daily intakes with the average
      requirement values of the Italian recommended dietary allowances. The present
      findings indicated that the dietary patterns of the Italian total diet were
      generally consistent with current Italian dietary recommendations for both macro
      and trace elements. The major concern was for Ca, for which daily intake was 76 %
      of the average recommendation for the Italian population. It should not be ruled
      out that there could be a potential risk of inadequate Fe intake in some segments
      of the population.

PMID- 14641972
TI  - Nutritional status of preschool Senegalese children: long-term effects of early
      severe malnutrition.
AB  - The prevalence of malnutrition remains high in many developing countries.
      However, data relating to the long-term effects of severe malnutrition,
      specifically, serum levels of biochemical indicators of nutritional status, are
      still scarce in the literature. Hence the present study aimed to investigate the
      nutritional, biological and growth status of Senegalese preschool children
      previously hospitalised for severe malnutrition. The study involved twenty-four 7
      year-old children who had suffered from marasmus 5 years earlier, twenty-four
      siblings living in the same household, and nineteen age-matched children living
      in the centre of Dakar. The siblings were of similar age to the post-marasmic
      children. Anthropometry, serum biochemical indicators of nutritional status,
      growth factors, and haematological and mineral parameters were measured. The
      prevalence of stunting and wasting was the same in the post-marasmic children as
      in the siblings. Body-fat and fat-free-mass (FFM) deficits in both groups were
      corroborated by abnormally low concentrations of transthyretin, osteocalcin,
      insulin-like growth factor (IGF)-1, and insulin-like growth factor-binding
      protein (IGFBP)-3. FFM was positively and significantly correlated with
      concentrations of IGF-1 and IGFBP-3. In the post-marasmic children, height for
      age was also correlated with IGF-1. Of the post-marasmic children, 53 % had Fe
      deficiency anaemia, as did 35 % of the siblings and 29 % of the controls. No
      significant associations were found between the serum concentrations of Ca, Cu,
      K, Mg, Na, P, Se, Zn and growth retardation. At 5 years after nutritional
      rehabilitation, the post-marasmic children remained stunted with nutritional
      indices significantly lower than the control children. However, these children
      were doing as well as their siblings except for minor infections.

PMID- 14641973
TI  - Body composition and physical activity in New Zealand Maori, Pacific and European
      children aged 5-14 years.
AB  - Body fatness and the components of energy expenditure in children aged 5-14 years
      were investigated. In a group of seventy-nine healthy children (thirty-nine
      female, forty male), mean age 10.0 (sd 2.8) years, comprising twenty-seven Maori,
      twenty-six Pacific Island and twenty-six European, total energy expenditure (TEE)
      was determined over 10 d using the doubly-labelled water method. Resting
      metabolic rate (RMR) was measured by indirect calorimetry and physical activity
      level (PAL) was calculated as TEE:RMR. Fat-free mass (FFM), and hence fat mass,
      was derived from the (18)O-dilution space using appropriate values for FFM
      hydration in children. Qualitative information on physical activity patterns was
      obtained by questionnaire. Maori and Pacific children had a higher BMI than
      European children (P<0.003), but % body fat was similar for the three ethnic
      groups. The % body fat increased with age for girls (r 0.42, P=0.008), but not
      for boys. Ethnicity was not a significant predictor of RMR adjusted for FFM and
      fat mass. TEE and PAL, adjusted for body weight and age, were higher in Maori
      than European children (P<0.02), with Pacific children having intermediate
      values. PAL was inversely correlated with % body fat in boys (r -0.43, P=0.006),
      but was not significantly associated in girls. The % body fat was not correlated
      with reported time spent inactive or outdoors. Ethnic-related differences in
      total and activity-related energy expenditure that might account for higher
      obesity rates in Maori and Pacific children were not seen. Low levels of physical
      activity were associated with increased body fat in boys but not in girls.

PMID- 14641974
TI  - Energy balance in patients with chronic obstructive pulmonary disease.

PMID- 14641976
TI  - Effect of temperature on the development of the aquatic stages of Anopheles
      gambiae sensu stricto (Diptera: Culicidae).
AB  - Global warming may affect the future pattern of many arthropod-borne diseases,
      yet the relationship between temperature and development has been poorly
      described for many key vectors. Here the development of the aquatic stages of
      Africa's principal malaria vector, Anopheles gambiae s.s. Giles, is described at
      different temperatures. Development time from egg to adult was measured under
      laboratory conditions at constant temperatures between 10 and 40 degrees C. Rate
      of development from one immature stage to the next increased at higher
      temperatures to a peak around 28 degrees C and then declined. Adult development
      rate was greatest between 28 and 32 degrees C, although adult emergence was
      highest between 22 and 26 degrees C. No adults emerged below 18 degrees C or
      above 34 degrees C. Non-linear models were used to describe the relationship
      between developmental rate and temperature, which could be used for developing
      process-based models of malaria transmission. The utility of these findings is
      demonstrated by showing that a map where the climate is suitable for the
      development of aquatic stages of A. gambiae s.s. corresponded closely with the
      best map of malaria risk currently available for Africa.

PMID- 14641977
TI  - Host-specific Wolbachia strains in widespread populations of Phlebotomus
      perniciosus and P. papatasi (Diptera: Psychodidae), and prospects for driving
      genes into these vectors of Leishmania.
AB  - A single strain of Wolbachia (alpha-proteobacteria, Rickettsiales) was found in
      widespread geographical populations of each of two Phlebotomus species, within
      which there was no indication of 'infectious speciation'. The two strains were
      identified by sequencing a fragment of wsp (a major surface protein gene),
      amplified by polymerase chain reaction from DNA extracted from the body parts of
      individual sandflies. Infection rates were high in the males and females of both
      sandflies, but they were lower for the B-group wPrn strain of Wolbachia in
      Phlebotomus perniciosus Newstead (60.3% overall) than for the A-group wPap strain
      in P. papatasi (Scopoli) (81.7%). Infections were frequent in the thorax, where
      Leishmania develops infective forms, as well as in the abdomen, where Wolbachia
      must infect the reproductive tissues to ensure its vertical transmission. These
      findings were related to knowledge of the population biology of Wolbachia in
      other insects, leading to the conclusion that this endosymbiont could be useful
      for driving transgenes through wild populations of both sandflies. This will
      require characterizing the cytoplasmic incompatibility phenotypes of Wolbachia
      sandfly combinations, as well as estimating for them the incidence of paternal
      transmission and the fidelity of maternal transmission. Paternal transmission is
      one explanation for finding a single Wolbachia strain associated with all
      mitochondrial haplotypes and lineages of each sandfly species. However, this
      distribution pattern could also result from multiple horizontal transmissions or
      the failure of wsp to provide strain markers.

PMID- 14641978
TI  - Seasonal variation in the effectiveness of the leaf-feeding beetle Zygogramma
      bicolorata (Coleoptera: Chrysomelidae) and stem-galling moth Epiblema strenuana
      (Lepidoptera: Tortricidae) as biocontrol agents on the weed Parthenium
      hysterophorus (Asteraceae).
AB  - Variation in the effectiveness of biocontrol agents on the weed Parthenium
      hysterophorus L. was evaluated at two properties (Mount Panorama and Plain Creek)
      in Queensland, Australia for four years (1996-2000) using a pesticide exclusion
      experiment. At Mount Panorama, higher levels of defoliation by the leaf-feeding
      beetle Zygogramma bicolorata Pallister and galling by the moth Epiblema strenuana
      Walker in 1996-97 coincided with an above average summer rainfall, but in the
      following three years with below average summer rainfall the defoliation and
      galling levels were significantly lower. Biocontrol had significant negative
      impact on the weed only in 1996-97 with no major impact in the following three
      years. At Plain Creek, galling by E. strenuana was evident in all the four years,
      but varied significantly between years due to non-synchrony between P.
      hysterophorus germination and E. strenuana emergence. At Plain Creek biocontrol
      had limited impact on the weed in 1996-97 and 1997-98, with no significant impact
      in the following two years. Over the 4-year period, defoliation and galling
      resulted in 70% reduction in the soil seed bank at Mount Panorama, but the
      reduction in the soil seed bank at Plain Creek due to galling was not
      significant. Effectiveness of Z. bicolorata and E. strenuana was dependent on
      weather conditions and as a result had only limited impact on the weed in three
      out of four years.

PMID- 14641979
TI  - Aphids do not avoid resistance in Australian lupin (Lupinus angustifolius, L.
      luteus) varieties.
AB  - Laboratory bioassays and field trials were used to characterize resistance to
      three aphid species (Myzus persicae (Sulzer), Acyrthosiphon kondoi Shinji, Aphis
      craccivora (Koch) in two aphid-resistant varieties (Kalya, Tanjil) and one
      susceptible variety (Tallerack) of Lupinus angustifolius L., and in one resistant
      variety (Teo) and one susceptible variety (Wodjil) of L. luteus L. Host selection
      tests in the glasshouse showed that alates of all three species preferred L.
      luteus to L. angustifolius, but provided no evidence that alates selected
      susceptible varieties over resistant. These results were supported by a field
      trial, which showed no difference in the number of colonizing A. kondoi alates
      collected from the resistant and susceptible lines of each lupin species, but
      there were significantly more late-instar nymphs and apterous adults on the
      susceptible lines. In laboratory host suitability experiments, there was much
      greater suppression of aphid growth and survival on Teo than on Kalya and Tanjil.
      In field trials, the numbers of aphids were generally lower on resistant compared
      to susceptible lines of both lupin species with one notable exception: M.
      persicae numbers were not lower on the resistant variety Tanjil compared to the
      susceptible variety Tallerack (L. angustifolius). These results suggest that the
      resistance mechanisms in both lupin species do not affect the selection of hosts
      by colonizing aphids, but rather are affecting the growth, survival and possibly
      reproduction of aphids after settling.

PMID- 14641980
TI  - The influence of soil heterogeneity on exploratory tunnelling by the subterranean
      termite Coptotermes frenchi (Isoptera: Rhinotermitidae).
AB  - The exploration of sand-filled arenas by workers of an entire colony of the
      Australian, subterranean foraging, tree-nesting termite, Coptotermes frenchi Hill
      was investigated under laboratory conditions. The first experiment tested whether
      termite exploration of sand was influenced by the presence of gaps or objects in
      the sand. Gaps and objects were chosen to represent soil heterogeneity in the
      urban environment: gaps to represent tunnels dug by other animals, perspex strips
      to represent cables and pipes, and wood strips to represent roots. Termites
      always chose to explore gaps thoroughly before they began tunnelling in the sand.
      Significantly more and longer tunnels were excavated from the end of gaps at the
      far end of the arenas, and relatively little tunnelling occurred around and along
      objects. Termite density was significantly greater around and along wood compared
      with perspex blocks. The second experiment tested whether termite exploratory
      tunnelling was influenced by soil moisture. The termites tunnelled slowly in dry
      sand, but after discovering a patch of wet sand, increased tunnelling five-fold
      until it was completely explored, after which activity declined. Energy and water
      conservation may be behind these patterns of exploratory tunnelling as well as
      those seen in large field studies, but caution is urged when interpreting small
      scale laboratory experiments to explain large scale field data.

PMID- 14641981
TI  - The causes and processes of the mid-summer population crash of the potato aphids
      Macrosiphum euphorbiae and Myzus persicae (Hemiptera: Aphididae).
AB  - Populations of many phloem-feeding aphid species in temperate regions increase
      exponentially in early summer and then 'disappear', usually over a time-scale of
      a few days, in July. To understand these dynamics, empirical investigation of the
      causes and modelling of the processes underlying population change are required.
      Numbers of the aphids Myzus persicae(Sulzer) and Macrosiphum euphorbiae (Thomas),
      monitored over three years in commercial potato fields in the UK, increased to a
      maximum of 2-2.5 per leaflet on 16 July in 1999 and 2001, and then declined to <
      0.25 per leaflet by 26 July. In 2000, aphid numbers remained very low (< 0.25 per
      leaflet) throughout the season. The onset of the crash in aphid numbers (16-19
      July in 1999 and 2001) was consistently associated with changes in the phloem
      amino acid composition of potato leaflets. Natural enemies, including syrphids,
      parasitoids, coccinellids, chrysopids and entomopathogenic fungi, increased in
      abundance throughout the sampling period. The incidence of winged emigrant aphids
      prior to the crash was low (< 10%). Experimental manipulation during 2001
      demonstrated that, during the crash period, the fecundity of aphids (caged on
      leaves to exclude natural enemies) was depressed by 25-45% relative to earlier in
      the season, and that presence of natural enemies reduced aphid numbers by up to
      68%. Using these data, an excitable medium model was constructed, which provided
      a robust description of aphid population dynamics in terms of plant development
      induced changes in aphid fecundity and temporal change in natural enemy pressure.

PMID- 14641982
TI  - Termite colony ontogeny: a long-term assessment of reproductive lifespan, caste
      ratios and colony size in Reticulitermes flavipes (Isoptera: Rhinotermitidae).
AB  - Thirty Reticulitermes flavipes (Kollar) colonies established by alates collected
      from two separate field sites were raised in the laboratory for eight years.
      Twenty-one of the colonies were founded by alates from one field source and nine
      from another, providing demographic data from two unrelated parental lineages.
      Colony totals ranged from 3620 to 11641 individuals, with no significant
      difference in size between lineages. Soldier caste proportion of the colony total
      and mean wet weights for workers, soldiers and kings were significantly different
      between the two lineages. This suggests that at least a portion of the
      variability observed in caste ratios and body size may be heritable. One founding
      reproductive had died in five of the colonies (17%); none lost both parents. The
      queenless colonies contained exclusively female replacement reproductives
      (neotenics); the kingless colony contained a female-skewed mixture of male and
      female neotenics. All the nests that lost a founding parent contained
      significantly more pre-alate nymphs than the nests with both a king and a queen.
      Comparisons with published reports of ontogenetic patterns in other termites and
      social insects are discussed.

PMID- 14641983
TI  - Genetic variation of Marchalina hellenica (Hemiptera: Margarodidae) sampled from
      different hosts and localities in Greece.
AB  - Random amplified polymorphic DNA (RAPD) analysis was applied to 120 individuals
      of Marchalina hellenica (Gennadius) representing six populations collected in
      northern, central and southern mainland Greece. One population was sampled on one
      species of fir tree and the others on two species of pine trees. Four random
      decamer primers were used to evaluate genetic variation among the populations
      examined. The results revealed intra- and interpopulation polymorphism both
      related to host type and region of origin. Phylogenetic analysis based on genetic
      distances estimated by the RAPD frequencies revealed an important genetic
      differentiation in samples collected on fir trees in southern Greece and to a
      lesser extent in samples from pine trees in central and northern Greece.
      Furthermore, considerable subdivision and restricted gene flow among the
      populations examined were observed. The results are discussed in relation to the
      biology and geographical distribution of M. hellenica in Greece.

PMID- 14641984
TI  - Feeding site selection by workers of the Formosan subterranean termite
      Coptotermes formosanus (Isoptera: Rhinotermitidae) - a re-analysis of field data
      from a mark-recapture study.
AB  - During the early stages of the development of termite baits, dyed paper was
      placed in specified feeding stations to ascertain whether a slow-acting toxicant
      could be placed in a few bait stations to be delivered to the entire colony
      members of the Formosan subterranean termite, Coptotermes formosanus Shiraki.
      Feeding frequency data, as measured by the dye concentration in individual
      termites, suggested the absence of feeding site fidelity. However, these results
      were often misinterpreted as random movement of termites that were marked and
      released for population estimate studies, or the random search of food in soil by
      subterranean termites. A computer simulation program was constructed to re
      examine this feeding frequency data, and confirmed the earlier conclusion that
      the lack of feeding site fidelity was the most likely explanation for the data.

PMID- 14641985
TI  - Host selection behaviour by adults of legume and cereal breeding populations of
      Sitophilus oryzae (Coleoptera: Curculionidae).

PMID- 14641986
TI  - Desipramine treatment reduces the long-term behavioural and neurochemical
      sequelae of early-life maternal separation.
AB  - Primate and rodent models of maternal separation have shown that repeated
      postnatal separation of young from the mother results in long-term changes to
      neurohormonal systems relevant to depression. To date, however, it remains
      unclear whether rodents that experience postnatal maternal separation display
      specific behavioural or biochemical features of depression in adulthood and
      whether these changes can be prevented by treatment with antidepressant drugs. We
      report here that maternally separated mice showed significantly shorter swim
      times on the forced swim test and significantly lower levels of brain-derived
      neurotrophic factor in dentate gyrus and CA3 regions of the hippocampus compared
      to control mice when assessed in adulthood. Neither of these differences was
      apparent in maternally separated mice that received chronic treatment with the
      antidepressant desipramine after maternal separation. These results suggest that
      intervention following early stress may eliminate the long-term vulnerability to
      behavioural and biochemical dysfunction that occurs following this early chronic
      stress.

PMID- 14641988
TI  - The impact of gefitinib on epidermal growth factor receptor signaling pathways in
      cancer.
AB  - The ErbB family of receptor tyrosine kinases, of which the epidermal growth
      factor receptor (EGFR) is the prototype, is associated with the formation and
      malignant progression of most of the common solid tumors. These molecules play a
      key role in a complex network of signal transduction pathways that function in
      normal development as well as in neoplastic transformation. The EGFR and other
      family members are therefore promising targets for new anticancer therapies. In
      normal tissues, EGFR-tyrosine kinase (TK) activity is strictly controlled.
      However, in tumor cells, there are multiple mechanisms that can lead to increased
      or inappropriate EGFR-TK activity, including altered expression of EGFR, its
      ligand, or interacting molecules; decreased deactivation through phosphatases or
      downregulation; or mutation of the EGFR protein. Novel therapeutic approaches
      aimed at inhibiting increased EGFR-TK activity include antibodies that block the
      extracellular ligand-binding site, antibody or ligand fusion proteins that
      specifically target toxins to the tumor cells, or small-molecule TK inhibitors
      (TKIs) that act intracellularly to block downstream signal transduction from
      EGFR. Studies have shown that such blockade can lead to reduced cellular
      proliferation, inhibition of survival signals, and inhibition of tumor metastasis
      and angiogenesis. Additionally, some agents, including EGFR antibodies and TKIs
      such as gefitinib have been demonstrated to be effective against various human
      solid tumors in preclinical models and have shown activity in advanced non-small
      cell lung cancer and other solid tumors.

PMID- 14641989
TI  - Biologically targeted treatment of non-small-cell lung cancer: focus on epidermal
      growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) has emerged in recent years as a key
      target of molecular therapy for solid tumors. The postembryonic role of EGFR is
      normally limited. In cancer, however, abnormal EGFR-tyrosine kinase (TK) activity
      plays a central role in many of the processes involved in tumor progression, such
      as proliferation, angiogenesis, invasiveness, decreased apoptosis, and loss of
      differentiation. Several different approaches have been taken to inhibit EGFR
      mediated activity in tumor cells, including monoclonal antibodies directed at the
      ligand-binding portion of the EGFR and small-molecule agents that directly
      inhibit the intracellular TK domain of EGFR. Two of these TK inhibitors,
      gefitinib and erlotinib (OSI-774, Tarceva ), have shown antitumor activity and
      good tolerability across several tumor types in early dose-finding clinical
      trials, particularly for non-small-cell lung cancer (NSCLC). In heavily
      pretreated patients with advanced NSCLC, gefitinib showed clinically significant
      tumor responses and symptom relief with good tolerability. Based on these
      results, gefitinib has now been approved for the third-line treatment of advanced
      NSCLC. The use of gefitinib in standard treatment programs or combined with other
      molecular targeted agents may substantially improve the outlook for patients with
      NSCLC or other types of solid tumors

PMID- 14641990
TI  - Pharmacokinetic evaluation of gefitinib when administered with chemotherapy.
AB  - Gefitinib is a small-molecule agent specifically targeted to inhibit the
      epidermal growth factor receptor-tyrosine kinase (EGFR-TK). Tumor responses have
      been achieved with gefitinib treatment in large, randomized monotherapy trials.
      In preclinical studies, gefitinib has shown additive and even supra-additive
      antitumor effects when combined with different cytotoxic agents. In phase I
      clinical trials, gefitinib was found to be well tolerated, with clinical efficacy
      observed well below the maximum tolerated dose. The pharmacokinetics of gefitinib
      allow it to be administered as a once-daily oral tablet. Several phase I studies
      have investigated the safety of gefitinib at daily doses of 250 mg or 500 mg in
      combination with chemotherapy agents for first-line treatment of a variety of
      common solid tumors. The potential for drug interactions between gefitinib and
      cytotoxic agents was evaluated through pharmacokinetic assessments. A randomized,
      crossover study investigated the interaction of gefitinib and
      carboplatin/paclitaxel in the treatment of advanced non-small-cell lung cancer
      (NSCLC). A second trial with an open-label design studied the combination of
      gefitinib with cisplatin/gemcitabine in patients with a variety of solid tumors,
      including NSCLC. In both pilot studies, the addition of gefitinib to chemotherapy
      did not increase the exposure of any of the chemotherapy agents tested. However,
      increased exposure to gefitinib was seen with the carboplatin/paclitaxel regimen.
      The addition of gefitinib to these chemotherapy regimens was generally well
      tolerated, and there was no apparent increase in higher-grade toxicity.
      Additional trials are evaluating gefitinib treatment in combination with
      chemotherapy.

PMID- 14641991
TI  - Molecular targeted agents in non-small-cell lung cancer.
AB  - Although advances in chemotherapy have provided some improvement in overall
      survival for patients with advanced non-small-cell lung cancer (NSCLC), outcomes
      remain poor. Several targeted therapies for lung cancer are in development, and
      it is hoped that these new approaches will continue to improve survival for
      patients with advanced NSCLC. These new therapies are targeted specifically to
      the molecular pathways and processes that characterize tumor growth and
      progression, including uncontrolled cell growth, invasion, metastasis,
      angiogenesis, and resistance to apoptosis. Some molecules, such as protein kinase
      C and the epidermal growth factor receptor-tyrosine kinase, play central roles in
      cellular activity and are involved in many of the different signaling pathways
      underlying malignant transformation. Other molecules are dedicated to a specific
      process, such as the role of vascular endothelial growth factor in angiogenesis.
      New approaches use a variety of technologies to target these molecules, including
      small-molecule inhibitors, antibodies, and antisense oligonucleotides, among
      others. Many of these therapies are currently being tested alone or in
      combination with each other and with standard treatments for a variety of tumors.
      This article summarizes data on treatment of NSCLC with some of the agents that
      are the furthest along in clinical development. It is possible to envision a
      future in which a combination of therapies treat lung cancer on multiple fronts,
      significantly enhancing tumor responses and improving survival beyond current
      expectations.

PMID- 14641992
TI  - Adjuvant systemic therapies in early-stage non-small-cell lung cancer.
AB  - Even when diagnosed at the earliest stages, non-small-cell lung cancer (NSCLC)
      has often begun to metastasize, leading to frequent systemic relapses and a poor
      prognosis. There is an urgent need for effective adjuvant systemic therapy in
      conjunction with surgery to reverse or control further growth of micrometastases
      in early-stage NSCLC. Several approaches have been investigated in the search for
      such a therapy, including various chemotherapies, applied preoperatively or
      postoperatively, chemopreventive agents, and molecular-targeted agents. This
      article presents an overview of clinical trials for these adjunctive therapies,
      including completed trials and trials whose results are anticipated. Although
      standard postoperative chemotherapy has been found to offer little benefit,
      likely because of the acquisition of resistance in advanced tumors, some clinical
      trials with neoadjuvant or alternative chemotherapies have produced encouraging
      results. Targeted agents such as the epidermal growth factor receptor/tyrosine
      kinase inhibitor gefitinib have shown early promise for effective disease
      control. A combination of these new approaches and standard therapy for NSCLC may
      improve long-term survival in patients with lung cancer

PMID- 14641993
TI  - Primary and secondary prevention of non-small-cell lung cancer: the SPORE Trials
      of Lung Cancer Prevention.
AB  - The aims of chemoprevention in lung cancer are to prevent the appearance of
      disease (primary prevention) and to stop or reverse the progression of
      premalignant lesions (secondary prevention). Until recently, there was little
      hope that these goals could be attained. However, the results achieved with
      tamoxifen in the prevention of breast cancer, and the emergence of new therapies
      specifically targeted to molecules involved in the pathogenesis of lung cancer
      have set the stage for investigation of these agents for chemoprevention of lung
      cancer. Two of these new molecular targeted agents are gefitinib, an inhibitor of
      epidermal growth factor receptor-tyrosine kinase activity, and tipifarnib
      (R115777, Zarnestra ), an inhibitor of the farnesyltransferase enzyme, which is
      required for the proper localization and function of the ras oncogene. Tumor
      responses and disease stabilization have been achieved with both agents in
      clinical trials. In the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL)-1
      and IDEAL-2 phase II trials, gefitinib was demonstrated to be effective for
      disease control in patients with advanced non-small-cell lung cancer. The SPORE
      (Specialized Program of Research Excellence) Trials of Lung Cancer Prevention
      (STOP) are 2 parallel studies that will investigate the potential effectiveness
      of gefitinib and tipifarnib in preventing the appearance and progression of
      premalignant lesions in former or current smokers with a history of smoking
      related cancer. These trials should provide information not only about the
      potential role of gefitinib and tipifarnib in lung cancer chemoprevention, but
      also about the molecular changes that underlie tumorigenesis and that may serve
      as markers of disease progression. The STOP trial objectives are to evaluate the
      effect of gefitinib and tipifarnib on histologic and biologic parameters in
      patients with evidence of sputum atypia, to evaluate various parameters as
      potential predictors of the effectiveness of these agents, and to evaluate the
      tolerability of these agents over a 6-month course of treatment. Histologic
      response, defined as prevention of appearance or progression of premalignant
      lesions, is the primary endpoint of these trials. New targeted molecular
      therapies such as gefitinib and tipifarnib may offer the opportunity to make
      chemoprevention a viable treatment modality in lung cancer as well as in other
      human solid tumors.

PMID- 14641994
TI  - Denaturing high-performance liquid chromatography for the detection of mutations
      and polymorphisms in UBE3A.
AB  - Angelman syndrome (AS) is caused by maternal deficiency of UBE3A, the gene
      encoding E6-AP ubiquitin-protein ligase. Our objectives were to develop
      conditions for denaturing high-performance liquid chromatography (dHPLC) analysis
      of UBE3A and to compare the sensitivity to direct genomic sequencing. Genomic DNA
      was obtained from 17 Angelman patients with known mutations and from 120 normal
      controls. DNA was amplified for the 10 coding exons and 6 upstream noncoding
      exons of UBE3A. Using dHPLC, the mutations previously identified in 17 Angelman
      patients were all easily detected using a single dHPLC condition for most exon
      containing fragments. An analysis of all 16 exons in 120 normal controls
      identified 15 other DNA alterations of varying frequency, all of which are
      assumed to be benign. We conclude that dHPLC is a reliable and convenient method
      for detecting mutations in UBE3A causing Angelman syndrome. No disease-causing
      mutations were found in the noncoding exons.

PMID- 14641995
TI  - Screening for DMD/BMD deletion carriers by fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) serves as an excellent alternative for
      direct detection of heterozygous deletions. Using a set of exon-specific cosmid
      DNA probes representing 18 exons, one-color FISH on metaphase and interphase
      preparations was performed to identify Duchenne/Becker muscular dystrophy
      (DMD/BMD) deletion carriers. The peripheral blood samples from 9 normal male or
      female controls and 5 females of independent DMD/BMD families, as well as 2
      amniotic fluid specimens and 2 chorionic villus samples (CVS) from normal
      pregnant females, were analyzed. Expected signals were displayed in 72-100% of
      peripheral blood lymphocyte metaphases or interphases, 60-70% of amniocyte
      interphases, and 95-99% of chorionic villus cell interphases. One suspected
      female was identified as a deletion carrier and two were excluded. The results
      indicated that metaphase and interphase FISH were both useful for detection of
      heterozygous deletions. FISH, in combination with other available techniques,
      allowed efficient screening of DMD/BMD deletion carriers. The study also offered
      preliminary results in support of an approach to prenatal diagnosis of potential
      fetal carriers.

PMID- 14641996
TI  - Calcium release from sarcoplasmic reticulum is facilitated in human myotubes
      derived from carriers of the ryanodine receptor type 1 mutations Ile2182Phe and
      Gly2375Ala.
AB  - Malignant hyperthermia (MH) is caused by increased calcium release from
      sarcoplasmic reticulum, triggered by volatile anesthetics or depolarizing muscle
      relaxants. Numerous mutations associated with MH have been detected in the
      skeletal muscle type ryanodine receptor gene (RyR1), but so far facilitated
      calcium release has only been demonstrated for a few of them. This is a
      prerequisite for confirming the causative role of an RyR1 mutation for MH.
      Calcium release from sarcoplasmic reticulum induced by 4-chloro-m-cresol (4CmC),
      caffeine, and halothane was determined in human myotubes by calcium imaging. The
      RyR1 Ile2182Phe mutation and the RyR1 Gly2375Ala mutation have been identified in
      individuals susceptible to MH. In myotubes of individuals carrying the RyR1
      Ile2182Phe or the RyR1 Gly2375Ala mutation, the EC(50) for caffeine and halothane
      was reduced; in the Ile2182Phe myotubes, the EC(50) for 4CmC was also reduced,
      all consistent with facilitated calcium release from the sarcoplasmic reticulum.
      From these data we conclude that both mutations are pathogenic for MH.

PMID- 14641997
TI  - High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts
      cystic fibrosis genetic testing.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 1,000
      different mutations in the cystic fibrosis transmembrane conductance regulator
      gene (CFTR). To determine the frequency of 70 common worldwide CFTR mutations in
      155 Euro-Brazilian CF patients and in 38 Afro-Brazilian CF patients, we used
      direct PCR amplification of DNA from a total of 386 chromosomes from CF patients
      born in three different states of Brazil. The results show that screening for
      seventy mutations accounts for 81% of the CF alleles in Euro-Brazilians, but only
      21% in the Afro-Brazilian group. We found 21 different mutations in Euro
      Brazilians and only 7 mutations in Afro-Brazilians. The frequency of mutations
      and the number of different mutations detected in Euro-Brazilians are different
      from Northern European and North American populations, but similar to Southern
      European populations; in Afro-Brazilians, the mix of CF-mutations is different
      from those reported in Afro-American CF patients. We also found significant
      differences in detection rates between Euro-Brazilian (75%) and Afro-Brazilian CF
      patients (21%) living in the same state, Minas Gerais. These results, therefore,
      have implications for the use of DNA-based tests for risk assessment in
      heterogeneous populations like the Brazilians. Further studies are needed to
      identify the remaining CF mutations in the different populations and regions of
      Brazil.

PMID- 14641998
TI  - A rapid and noninvasive method for detecting tissue-limited mosaicism: detection
      of i(12)(p10) in buccal smear from a child with Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome (PKS), a rare disorder, is characterized by tissue
      limited or tissue-specific mosaicism. The characteristic chromosome abnormality
      associated with PKS is i(12p), which is seen predominantly in skin fibroblast
      cultures. Diagnosis of i(12p) has been carried out on buccal smears before and
      was shown to be an easy and feasible method. All previously published studies
      used alpha-satellite probes for the diagnosis and as such have several pitfalls.
      Our approach, using dual-color, locus-specific probes, has high specificity and
      sensitivity for the diagnosis of i(12p). Using statistical analysis, we have also
      confirmed that the signal pattern in interphase nuclei is consistent with
      isochromosome 12p.

PMID- 14641999
TI  - Genetic testing for hemochromatosis: attitudes and acceptability among young and
      older adults.
AB  - Hemochromatosis is a genetic disorder of iron overload common in persons of
      northern European descent. We examined attitudes about testing for
      hemochromatosis in 118 young adults (YA) (19.7 years +/- 1.9) and 50 older adults
      (OA) (58.5 years +/- 13.7). Participants read about hemochromatosis and two
      related tests: transferrin saturation measurement (iron test) and HFE genotyping
      (HFE test). Interest in each test and attitudes about genetic testing were
      assessed. More than 80% of all participants were willing to undergo either test,
      if offered. A majority preferred the iron test because of the information it
      provides about current health. A majority of participants identified at least one
      benefit of genetic testing, with improved health through early
      detection/prevention being most common. YA were more likely to report
      disadvantages of genetic testing (p < 0.001) and were more concerned about
      potential negative psychological effects (p < 0.005). OA were more concerned
      about potential discrimination (p < 0.0001). These findings suggest that young
      and older adults view genetic testing as beneficial and would accept HFE testing
      were it offered as part of a screening program.

PMID- 14642000
TI  - Rapid prenatal testing for human beta-glucuronidase deficiency (MPS VII).
AB  - Prenatal diagnosis for the lysosomal storage disorders is typically achieved by
      enzymatic analysis of the relevant lysosomal enzyme in cultured amniocytes or
      chorionic villi. While prenatal diagnosis of some genetic diseases can be done by
      analysis of pertinent metabolites in amniotic fluid, there are few data regarding
      prenatal diagnosis of lysosomal disorders by enzyme analysis of amniotic fluid.
      Prenatal diagnosis by enzyme analysis of amniotic fluid has the potential
      advantage of providing a more rapid prenatal test result. In this study we
      describe an assay for the prenatal diagnosis of the mucopolysaccharidosis beta
      glucuronidase deficiency (MPS VII; MIM #253220) using amniotic fluid and we
      confirm its reliability in detecting an affected fetus in an at-risk pregnancy by
      enzyme analysis of cultured amniocytes and fetal fibroblasts. Because MPS VII is
      rare and few instances of prenatal diagnosis for this and nearly all other
      lysosomal disorders have been accomplished by enzyme analysis of amniotic fluid,
      confirmation of results obtained from enzyme analysis of amniotic fluid should be
      carried out by enzyme or mutation analysis using cultured amniocytes or chorionic
      villus specimens.

PMID- 14642001
TI  - Sex chromosome analysis in Turner Syndrome by a pentaplex PCR assay.
AB  - In this study, we describe a pentaplex PCR to determine the parental origin of
      the X chromosome and the presence of mosaicism, via amplification of four
      polymorphic markers located along the X chromosome (DXS10011, DXS6807, HUMARA,
      DXS101) and the X-Y amelogenin marker, in 41 families having a daughter with
      Turner Syndrome. Our results confirmed the cytogenetic findings and we found that
      the parental origin of the single X chromosome to be maternal in 84% of cases.

PMID- 14642002
TI  - Denaturing high-performance liquid chromatography quickly and reliably detects
      cardiac ion channel mutations in long QT syndrome.
AB  - Multiple mutations in several ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1,
      KCNE2, and KCNJ2) have been shown to cause autosomal dominant long QT syndrome
      (LQTS), a familial cardiac disorder that causes syncope, seizures, and sudden
      death. Due to their multiple loci and considerable size, mutation detection in
      these genes represents a challenge that is only partially met by the conventional
      screening method of single-stranded conformational polymorphism (SSCP). The
      recently introduced denaturing high-performance liquid chromatography (dHPLC)
      offers a promising new method for a fast and sensitive analysis of PCR-amplified
      DNA fragments. To test the applicability of dHPLC in the molecular diagnosis of
      LQTS, we first assessed a cohort of 192 patients from our International LQTS
      Registry for 14 previously identified mutations (including 10 different missense
      mutations, 1-bp, 2-bp, 3-bp, and 9-bp deletion mutations), and 2 polymorphisms in
      the LQTS potassium and sodium channel genes. Applying empirically determined exon
      specific melting profiles, all mutations (including four previously undetectable
      by SSCP) were readily identified by dHPLC. We conclude that the dHPLC technology
      is a highly sensitive and efficient method for the molecular analysis of LQTS,
      and the same PCR amplicons developed for SSCP testing can be directly used for
      dHPLC assay.

PMID- 14642003
TI  - High incidence of two methylenetetrahydrofolate reductase mutations (C677T and
      A1298C) in Hispanics.
AB  - Mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and coagulation
      factors II and V genes have been found at high frequencies in European and
      American Caucasian populations and are associated with increased risk for
      thrombophilia, premature coronary artery disease, and a variety of adverse
      pregnancy outcomes. Hispanic populations in the United States exhibit high levels
      of some of these conditions, so we initiated a population-based study to
      determine the frequency of these mutations (MTHFR C677T and A1298C, Factor II
      G20210A and Factor V G1691A) in this group. We find comparable frequencies of the
      Factors II and V mutations, but a high incidence of the two MTHFR mutations in a
      diverse sample of American Hispanics compared to those reported in Caucasians.
      Prospective studies of Hispanic women with these mutations and pregnancy outcomes
      will establish if there is a causal relationship.

PMID- 14642004
TI  - Characterization of genomic variants in CSH1 and GH2, two candidate genes for
      Silver-Russell syndrome in 17q24-q25.
AB  - Silver-Russell syndrome (SRS) is a syndrome of severe pre- and postnatal growth
      retardation and typical dysmorphic features. Rare chromosomal aberrations have
      been reported in SRS; among these are two balanced translocations involving 17q24
      q25. Recently, we described a patient with a paternally inherited heterozygous
      deletion of the chorionic somatomammotropin hormone 1 (CSH1) gene. The CSH1 gene
      is member of the growth hormone (GH) gene cluster on 17q, which consists of two
      growth hormone genes and three CSH genes. Genomic alterations in the GH cluster
      are well known, causing different phenotypes depending on the size of the
      deletion and the genes involved. By screening 63 SRS cases with marker D17S254,
      we have detected 2 further patients with a heterozygous deletion in the GH
      cluster. Quantitative analysis using restriction assays confirmed these findings.
      Additionally, in a cohort of 17 patients with isolated intrauterine and postnatal
      growth retardation, we detected a further patient to be carrier of a CSH1
      deletion. Screening of 141 unrelated controls revealed hemizygosity in one person
      for which data on growth were not available. We additionally analyzed our cohort
      of SRS patients for mutations in CSH1 and its 3' neighbour GH2. However, analyses
      failed to reveal any pathogenic mutation. While the central role of GH1 in human
      growth is well established, the physiological roles of CSH1 and other components
      of the cluster are unclear. The increased prevalence of hemizygosity of CSH1 in
      our population in comparison to controls indicates a role for CSH1
      haploinsufficiency in the etiology of growth retardation. Investigation of CSH1
      deletions in further SRS and growth retarded patients will enable us to establish
      under which circumstances haploinsufficiency of CSH1 is likely to result in
      clinical changes.

PMID- 14642005
TI  - Plasminogen activator inhibitor-1 polymorphism in women with pre-eclampsia.
AB  - We determined whether or not genetic variability in the promoter region of the
      gene encoding plasminogen activator inhibitor-1 (PAI1) contributes to individual
      differences in susceptibility to the development of preeclampsia. The study
      involved 133 preeclamptic and 115 healthy control pregnant women who were
      genotyped for a single-nucleotide insertion/deletion polymorphism (4G/5G) at
      position -675 in the PAI1 gene promoter. Furthermore, the frequencies of the
      alleles in the general middle-aged population are presented for comparison. Chi
      square analysis was used to assess genotype and allele frequency differences
      between preeclamptic women and controls. A similar allelic distribution of PAI1
      4G/5G polymorphism was observed in the two groups, with the frequency of the
      variant 4G allele being 50.4% in the preeclampsia group and 54.3% in the control
      group (p = 0.377; OR = 0.85, 95% CI = 0.60-1.22). Accordingly, the genotype
      distribution of the PAI1 4G/5G polymorphism in the preeclamptic and control
      groups was found to be similar (p = 0.68). Overall, this genotype data on fertile
      women is almost identical to that in the general middle-aged Finnish population.
      The 4G/5G polymorphism of the PAI1 gene promoter is unlikely to be a major
      genetic predisposing factor as regards preeclampsia in subjects from eastern
      Finland. These results are not suggestive of an important contribution of the
      PAI1 genotype on preeclampsia across populations.

PMID- 14642006
TI  - Validation of dHPLC for molecular diagnosis of beta-thalassemia in Southern
      Italy.
AB  - Beta-thalassemia, the most common hereditary anemia in the Mediterranean area,
      results from over 200 causative mutations in the beta-globin locus. The aim of
      this study was to validate a denaturing high-performance liquid chromatography
      (dHPLC)-based assay for postnatal and prenatal molecular diagnosis of beta
      thalassemia in Southern Italy. Sixty beta-thalassemic patients, affected either
      by thalassemia intermedia or thalassemia major, were analyzed in a blind study.
      We also carried out prenatal molecular diagnosis in 12 couples at-risk for having
      affected offspring. Chorionic villi samples were subjected to dHPLC analysis upon
      molecular characterization of the parental beta-globin alleles. Direct sequence
      analysis was used to validate each result, showing an accuracy rate of 100% for
      dHPLC. Overall, our protocol was able to identify the responsible mutations in
      all 96 analyzed subjects (including 12 prenatals in at-risk pregnancies),
      detecting the eight most common mutations in Southern Italy. Three rare mutations
      (one of which, reported here for the first time) that standard mutation detection
      methods failed to reveal, were also identified. dHPLC assay proved to be a
      reliable, rapid, and sensitive method for detecting both common and rare
      mutations within the beta-globin gene. Because of this property our protocol has
      the potential to be implemented for mutational screening in different areas of
      high prevalence for beta-thalassemia.

PMID- 14642008
TI  - Obsessive-Compulsive disorder, Tourette's disorder, or pediatric autoimmune
      neuropsychiatric disorders associated with Streptococcus in an adolescent?
      Diagnostic and therapeutic challenges.

PMID- 14642009
TI  - Opportunity from crisis: how medical cost offset helps our patients and may help
      save the system.

PMID- 14642011
TI  - The Joaquim Puig-Antich legacy.

PMID- 14642012
TI  - Growth hormone response to growth hormone-releasing hormone and clonidine in
      young monkeys: correlation with behavioral characteristics.
AB  - Blunted growth hormone (GH) release in response to stimulation by a secretagogue
      has been widely reported in both children and adults with anxiety and depressive
      disorders. Blunted GH responsiveness appears to be a stable characteristic of an
      individual, suggesting that it may be useful as a biological marker that would
      allow early recognition of these disease processes. Another potential biological
      marker for anxiety disorders is the temperamental construct of behavioral
      inhibition. Children identified as being behaviorally inhibited early in life are
      more likely than less inhibited children to suffer from anxiety disorders later
      in life (Biederman et al. 1993; Hirshfeld et al. 1992). If blunted GH
      responsiveness to pharmacological challenge and behavioral inhibition are markers
      of anxiety and depressive disorders, then it would follow that they would coexist
      in a subset of individuals. However, such prospective studies in clinically
      normal young children are difficult to perform. Therefore, in this study, we
      examined GH responsiveness and temperament in a group of 38 young rhesus monkeys
      (ages 3-6 months). Monkeys received an intravenous dose of 10 microg/kg of growth
      hormone-releasing hormone (GHRH) and 5 microg/kg of clonidine, combined, to
      assess GH response to stimulation. Behavioral reactivity in a fearful situation
      was assessed using the Human Intruder Test developed by Kalin et al. (1991). This
      test measures response to a potentially threatening stimulus (a human stranger
      making direct eye contact). Results showed a population distribution of GH
      response to GHRH and clonidine ranging from 120 ng/mL/90 minutes to 3,000
      ng/mL/90 minutes. There was no difference in GH response in males versus females
      or any significant effect of age on GH response. There was a significant
      correlation between GH responsiveness and the time spent reacting to the intruder
      in the Human Intruder Test. Monkeys with lower GH responsiveness reacted less to
      the intruder (p < 0.01). Additionally, when monkeys were classified based on
      their reactivity in the Human Intruder Test, behaviorally nonreactive monkeys had
      significantly lower GH responsiveness than behaviorally reactive monkeys (p <
      0.005). These data provide evidence that there are inherent differences in GH
      responsiveness to stimulation in young rhesus monkeys and that low GH
      responsiveness is linked to low behavioral reactivity, which may be a form of
      behavioral inhibition. Further studies will be necessary to determine if the
      characteristics of low GH responsiveness and low behavioral reactivity predict an
      increased propensity to develop anxious or depressive behaviors over the course
      of the life span.

PMID- 14642013
TI  - Measuring mood and complex behavior in natural environments: use of ecological
      momentary assessment in pediatric affective disorders.
AB  - This article describes the theoretical background and methodology of ecological
      momentary assessment (EMA) and reports results from a pilot study using EMA
      techniques in 16 children and adolescents with affective disorders and 5 subjects
      who were healthy and at low risk to develop future affective disorders. Multiple
      daily assessments of the subjects' mood, thoughts, and behaviors were performed
      in their natural environments using brief interviews on cellular phone calls by
      the study staff and by wrist actigraphy. The pilot results demonstrated that the
      EMA methodology is feasible in this population, as 17 of 21 subjects were able to
      complete the entire 8-week protocol. The potential usefulness of the EMA
      methodology is illustrated by specific case reports. Potential applications of
      the EMA methodology to the study of neurobehavioral systems and the
      pathophysiology of pediatric affective disorders are discussed.

PMID- 14642014
TI  - Definitions of rapid, ultrarapid, and ultradian cycling and of episode duration
      in pediatric and adult bipolar disorders: a proposal to distinguish episodes from
      cycles.
AB  - OBJECTIVE: To propose terminology to distinguish cycles from episodes in children
      and adults with bipolar disorder (BP). METHODS: To examine current definitions of
      rapid cycling and episodes in both child and adult BP, an Internet search of the
      MEDLINE database was conducted. RESULTS: Investigations of rapid cycling in
      adults used the terms cycle and episode interchangeably to describe discrete
      periods of mood disorders. Two studies of children and one study of adults with
      BP, however, reported cycles occurring daily (ultradian cycling) or every few
      days (ultrarapid cycling). Without definitions to differentiate cycles from
      episodes, determining the overall duration of illness in subjects who experience
      ultrarapid or ultradian cycling is not possible. For example, a child cycled
      twice a day, every day, for 365 days (1 year). With the terminology currently in
      use, it is unclear whether this should be described as a single episode that had
      a duration of 365 days or as approximately 730 episodes (2 cycles per day x 365
      days), each less than 24 hours in duration. Moreover, adults with BP may have
      more intermittent pathology than children (e.g., adults may cycle 4 days per
      week, versus children may cycle 7 days per week). CONCLUSION: The following
      definitions are proposed. (1) Episodes will be defined by (a) the duration from
      onset to offset of a period of at least 2 weeks in length during which only one
      mood state persists or (b) the duration from onset to offset of a period of
      ultrarapid or ultradian cycling for at least 2 weeks. (2) Cycles will be defined
      by mood switches occurring daily or every few days during an episode. Further
      research will be needed to elucidate potential differences between child and
      adult cycling patterns.

PMID- 14642015
TI  - Does stimulant treatment place children at risk for adult substance abuse? A
      controlled, prospective follow-up study.
AB  - The sensitization hypothesis posits a neuroadaptation model in which exposure to
      stimulants results in dopamine system alterations that, in turn, increase
      sensitivity to the reinforcing effects of the previously experienced drug. This
      study examines whether stimulant treatment in childhood confers increased risk
      for substance use and abuse in later life, as the model predicts. Children, ages
      7-12 years, with developmental reading disorders but no other psychiatric
      diagnoses were randomly assigned to methylphenidate treatment (n = 43) or
      matching placebo (n = 66) for 12-18 weeks. At 16-year follow-up (mean age 26
      years), 94% of probands and 129 normal comparisons were evaluated by trained
      clinicians who were blind to group and treatment status. There were no
      significant differences between groups on the prevalence of substance use
      disorder (abuse or dependence) for any of the seven drug categories studied.
      There were no significant group differences among substance abusers regarding age
      at onset, duration, or number of episodes of substance abuse and dependence.
      Significantly more normals (60%) than treated (46%) and untreated probands (41%)
      ever used stimulants in adolescence or adulthood. Findings from this randomized
      trial contradict the notion that stimulant treatment in childhood leads to
      substance use or abuse in later life. The sensitization hypothesis is not
      supported.

PMID- 14642016
TI  - Growth hormone response to guanfacine in boys with attention deficit
      hyperactivity disorder: a preliminary study.
AB  - OBJECTIVE: This preliminary study evaluated a method for assessing central
      noradrenergic function in children via the growth hormone response to a single
      dose of the alpha-2 adrenergic receptor agonist guanfacine and examined whether
      this measure distinguishes between attention deficit hyperactivity disorder
      (ADHD) boys with and without reading disabilities (RD). METHODS: Plasma growth
      hormone was assessed before and after the oral administration of guanfacine and
      placebo in boys with ADHD who were divided into subgroups based on the presence
      (n = 3) or absence (n = 5) of RD. RESULTS: Guanfacine and placebo conditions did
      not differ at baseline, but peak growth hormone was significantly higher
      following guanfacine. The increase in growth hormone following guanfacine was
      significantly greater in boys without RD as compared to those with RD, with no
      overlap between the groups. CONCLUSIONS: Consistent with findings using
      peripheral measures of noradrenergic function, these preliminary data suggest
      that ADHD boys with and without RD may differ in central noradrenergic function.

PMID- 14642017
TI  - Quetiapine treatment of children and adolescents with Tourette's disorder.
AB  - OBJECTIVE: The purpose of this study was to investigate the short-term safety and
      effectiveness of quetiapine in the treatment of children and adolescents with
      Tourette's disorder. METHODS: This was an 8-week, open-label trial that included
      12 subjects with a mean age of 11.4 +/- 2.4 years. The subjects were seen every
      week throughout the study. RESULTS: Clinical responses, as measured by the
      Turkish version of the Yale Global Tic Severity Scale, revealed a statistically
      significant reduction in tic scores ranging from 30-100%. Mean dose of quetiapine
      at the end of the study was 72.9 +/- 22.5 mg/day. Three subjects complained of
      sedation in the first week of treatment. CONCLUSIONS: The favorable results of
      this open-label study should be interpreted with caution due to the uncontrolled
      nature of the study. Spontaneous waxing and waning of symptoms should also be
      considered. Further controlled studies are required.

PMID- 14642018
TI  - A 1-year open-label trial of olanzapine in school-age children with
      schizophrenia.
AB  - OBJECTIVE: To determine the response of children with childhood-onset
      schizophrenia to a 1-year prospective, open-label trial of olanzapine. METHODS:
      Twenty children (age range 6-15 years) with childhood-onset Diagnostic and
      Statistical Manual of Mental Disorders (fourth edition) schizophrenia
      participated. The treating clinician was free to vary or discontinue dosing and
      use additional medications. Symptoms were assessed by the Brief Psychiatric
      Rating Scale-Child version (BPRS-C), Scale for the Assessment of Positive
      Symptoms, and Scale for the Assessment of Negative Symptoms. Extrapyramidal
      symptoms, akathisia, temperature, and weight were monitored. RESULTS: BPRS-C
      subscales of thought disturbance and psychomotor excitation, and the Scale for
      the Assessment of Positive Symptoms demonstrated significant decreases by 6 weeks
      of treatment; BPRS-C anxiety and the Scale for the Assessment of Negative
      Symptoms (SANS) showed significant improvement after 1 year of treatment. Seventy
      four percent of subjects were considered treatment responders, with a greater
      than 20% reduction in total BPRS-C score and overall impairment of mild or
      better. Weight gain (body mass index) was above that expected for normal
      development in every child. No child developed neuroleptic-related dyskinesias.
      Seventy-four percent (n = 14) of patients completed this 1-year, open-label
      trial. Of the 5 subjects who discontinued, weight gain was noted as the reason
      for 4 subjects. CONCLUSIONS: Olanzapine appears useful in the treatment of
      childhood-onset schizophrenia, although there may be a delayed onset of benefit
      for anxiety and negative symptoms. Weight gain is problematic, but the emergence
      of dyskinesias may be rare. Additional controlled trials are indicated.

PMID- 14642019
TI  - Olanzapine treatment in chronic drug-resistant childhood-onset schizophrenia: an
      open-label study.
AB  - The use of typical antipsychotics is limited in children with schizophrenia,
      owing to the high rate of response failure and early appearance of extrapyramidal
      syndromes as well as tardive and withdrawal dyskinesia. The aim of the present
      study was to examine the effectiveness of the atypical antipsychotic olanzapine
      in the treatment of childhood-onset schizophrenia. The study sample included nine
      children hospitalized for schizophrenia who had proven refractory to treatment
      with at least two antipsychotic drugs. Olanzapine was administered after a 2-week
      washout period in gradually increasing doses to a maximum of 5 mg/day on day 5
      and 10 mg/day in week 3; six patients received up to 20 mg/day as of week 5. The
      duration of the study was 12 weeks. Patient psychiatric status was measured with
      three scales at onset of therapy and thereafter once weekly. Patients also
      underwent regular blood, laboratory, and liver function tests, and we also
      monitored their blood pressure and weight and performed electrocardiography and
      electroencephalography. A reduction in all psychopathology scores was obtained at
      12 weeks from baseline. All extrapyramidal symptoms of previous medications
      resolved, and there were no new incidents. Side effects were mild. There were no
      adverse changes in blood chemistry, hematological tests, or electrocardiography
      parameters, but the treatment was associated with a significant weight gain (6.10
      +/- 3.25 kg). At 1-year follow-up, the improvement in psychiatric symptoms was
      sustained in eight children. We conclude that olanzapine may have potential as a
      first-line drug in the treatment of drug-resistant childhood-onset schizophrenia.
      Large-scale, double-blind, placebo-controlled comparative studies are needed to
      clarify the role of the various atypical antipsychotics in both treatment
      resistant and treatment-naive populations with psychotic symptoms/disorders.

PMID- 14642020
TI  - Effectiveness, safety, and tolerability of risperidone in adolescents with
      schizophrenia: an open-label study.
AB  - Data on risperidone's efficacy and tolerability in adolescents with schizophrenia
      are scarce. We found only one prospective, open-label study in this population.
      The aim of this open-label, prospective study was to estimate the effectiveness,
      safety, and tolerability of risperidone treatment in adolescents with first
      episode schizophrenia. Subjects were adolescent inpatients diagnosed with
      Diagnostic and Statistical Manual of Mental Disorders (fourth edition) first
      episode schizophrenia by the Kiddie Schedule for Affective Disorders and
      Schizophrenia for School-Age Children-Present Episode version. Most of the
      patients (10/11) were drug naive. Improvement was assessed during the first 6
      weeks of treatment using the Positive and Negative Syndrome Scale (PANSS), the
      Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression (CGI)
      scale. Side effects were monitored using the Abnormal Involuntary Movement Scale,
      the Simpson-Angus Scale, the Barnes Akathisia Rating Scale, and the Udvalg for
      Kliniske Undersogelser Side Effect Rating Scale. Eleven adolescents between 15.5
      and 20 years of age (mean = 17.27, SD = 1.27 years) were included in this study.
      Risperidone in an average dose of 3.14 mg/day (SD = 1.60 mg/day) produced a
      significant improvement on the total PANSS score (28%, p < 0.01), BPRS score
      (30.11%, p < 0.01), and CGI-Severity score (31.36%, p < 0.01). Risperidone was
      ineffective in the treatment of negative signs as assessed by the PANSS. The
      major side effects were extrapyramidal side effects, somnolence, depression, and
      weight gain. In conclusion risperidone appears to be a safe, acceptably
      tolerated, and effective antipsychotic medication for the treatment of adolescent
      onset schizophrenia.

PMID- 14642021
TI  - An open trial of fluoxetine for adolescents with bulimia nervosa.
AB  - OBJECTIVE: This open clinical trial examined the feasibility, tolerability, and
      efficacy of treating adolescents who suffer from bulimia nervosa with fluoxetine.
      METHODS: Ten adolescents, ages 12-18 years received 8 weeks of fluoxetine 60
      mg/day with supportive psychotherapy. Primary outcome measures included
      frequencies of binge eating and purging and ratings on the Clinical Global
      Impressions-Improvement scale (CGI-I). Secondary outcome measures included self
      report measures of eating disorder, depression, and anxiety symptoms. Safety and
      tolerability of this dose of fluoxetine were also assessed. RESULTS: Average
      weekly binges decreased significantly from 4.1 +/- 3.8 to 0 (p < 0.01). Average
      weekly purges decreased significantly from 6.4 +/- 5.2 to 0.4 +/- 0.9 (p <
      0.005). All patients improved on the CGI-I scale, with 20% rated as much
      improved, 50% improved, and 30% slightly improved. All subjects tolerated the 60
      mg dose of fluoxetine, and there were no dropouts due to adverse effects from the
      medication. DISCUSSION: Fluoxetine is generally well tolerated and may be an
      effective treatment option for adolescents with bulimia nervosa.

PMID- 14642022
TI  - The Kutcher Adolescent Depression Scale: assessment of its evaluative properties
      over the course of an 8-week pediatric pharmacotherapy trial.
AB  - OBJECTIVE: Self-report instruments commonly used to assess depression in
      adolescents have limited or unknown psychometric properties in this age group. We
      report the evaluative properties of the Kutcher Adolescent Depression Scale
      (KADS), a self-report scale designed specifically for identifying depressed
      adolescents and for monitoring symptom severity over time. METHODS: One hundred
      and six adolescents with major depression disorder (MDD) enrolled in an 8-week,
      double-blind, placebo-controlled study of paroxetine. Efficacy assessments were
      conducted on days 0 (baseline), 7, 14, 21, 28, 42, and 56 using the self-rated
      KADS and the clinician-rated Children's Depression Rating Scale-Revised (CDRS-R),
      Clinical Global Impression (CGI) of severity, and Global Assessment of
      Functioning (GAF) scale. The data were initially examined to establish which of
      the 16 KADS items showed greatest sensitivity to change. Subsequent analyses then
      compared the evaluative properties of three versions of the KADS: the full-length
      KADS, a six-item subscale previously established as a screening tool, and an 11
      item subscale optimized for sensitivity to change. RESULTS: Within-subject
      correlations among subjects' KADS scores and their clinician-rated scale scores
      showed that clinician-rated changes in severity were significantly better
      corroborated by the 11-item KADS (mean correlations with the CDRS-R, CGI, and
      GAF: r = 0.69, 0.60, and -0.70, respectively) than by the six-item KADS (r =
      0.62, 0.56, and -0.63, respectively) and at least as well corroborated as by the
      full-length KADS (r = 0.64, 0.56, and -0.67, respectively). Furthermore, in terms
      of mean percentage change in scores from day 0 to day 56, the 11-item KADS (59%)
      significantly outperformed the full-length KADS (46%) and all three clinician
      rated scales (43%, 37%, and 29%, respectively) and at least matched the
      performance of the six-item KADS (56%). CONCLUSIONS: These results suggest that
      the 11-item self-rated KADS is a sensitive measure of treatment outcome in
      adolescents diagnosed with MDD.

PMID- 14642023
TI  - Diagnosis and measurement of anxiety disorder in adolescents: a review of
      commonly used instruments.
AB  - As part of a comprehensive review of clinical research tools used in adolescent
      psychiatric disorders, a survey of 200 recent studies of adolescent anxiety
      (publication dates of December 1994 to May 2001) identified 70 different
      diagnostic and symptom measurement instruments. The design features and
      psychometric properties of the 15 most commonly used instruments were reviewed,
      and their strengths and weaknesses were evaluated. The conclusions arising from
      this review are: (1) too many different instruments are being used by
      investigators; (2) more than 20% of studies did not report the use of
      developmentally appropriate (i.e., child/adolescent-specific) diagnostic
      instruments; (3) another 15% of these studies relied on diagnostic instruments
      that demonstrate substantial weaknesses in reliability and validity; (4) the
      concordance between anxiety disorder diagnoses from different interview schedules
      is unknown; (5) the relative validity of diagnoses and ratings of anxiety
      severity based on information yielded by parents versus information yielded by
      adolescents is unclear; (6) clinician-rated symptom severity scales specific to
      anxiety disorder are rarely utilized; (7) the most commonly used self-report
      measures discriminate poorly between anxiety and depression, and their items are
      not indexed to specific anxiety disorders; and (8) some newer self-report anxiety
      instruments discriminate well between anxiety and depression and have diagnostic
      validity for specific anxiety disorders.

PMID- 14642024
TI  - Clozapine-induced neutropenia in children: management with lithium carbonate.
AB  - Clozapine, an atypical antipsychotic, is the most effective medication for
      treatment-resistant schizophrenia, but its use is limited by the high risk of
      neutropenia and agranulocytosis. In children, the rate of clozapine-induced
      neutropenia is even higher than in adults. We report two cases of children 7- and
      12-years old diagnosed with very early onset schizophrenia, who developed
      neutropenia when treated with clozapine. In both cases addition of lithium
      carbonate elevated the white blood count (WBC) allowing clozapine rechallenge.
      WBC and total neutrophil count remained stable long-term with coadministration of
      clozapine (400-425 mg per day) and lithium with the blood level of 0.8-1.1
      microg/mL. This report supports the use of adjunct lithium for clozapine-induced
      neutropenia as a safe and successful strategy in children.

PMID- 14642025
TI  - Shockwave lithotripsy: anecdotes and insights.
AB  - Shockwave lithotripters have evolved considerably since the introduction of the
      Dornier HM3 machine 20 years ago. Although shockwave lithotripsy (SWL) remains
      the preferred treatment for the majority of symptomatic upper urinary-tract
      calculi, newer lithotripters are not as effective and may have a higher risk of
      side effects. Lack of progress in lithotripter evolution is attributable to
      inadequate understanding of how and why shockwaves produce effects on stone and
      tissue. Current knowledge suggests that stones fragment by the mechanisms of
      compression fracture, spallation, squeezing, and acoustic cavitation, while
      tissue damage from shockwaves is secondary to cavitation and non-cavitational
      forces such as sheer stress. It appears likely that most tissue damage from
      shockwaves is caused by cavitation. As the understanding of SWL matures, new
      lithotripter designs may emerge that truly represent an improvement on the
      original Dornier HM3 machine.

PMID- 14642026
TI  - Robotic surgery: urologic implications.
AB  - Current medical robots have nothing in common with the anthropomorphic robots in
      science fiction classics. They are in fact, manipulators, working on a master
      slave principle. Robots can be defined as "automatically controlled multitask
      manipulators, which are freely programmable in three or more spaces." The success
      of robots in surgery is based on their precision, lack of fatigue, and speed of
      action. This review describes the theory, advantages, disadvantages, and clinical
      utilization of mechanical and robotic arm systems to replace the second assistant
      and provide camera direction and stability during laparoscopic surgery. The
      Robotrac system (Aesculap, Burlingame, CA), the First Assistant (Leonard Medical
      Inc, Huntingdon Valley, PA), AESOP (Computer Motion, Goleta, CA), ZEUS (Computer
      Motion), and the da Vinci (Intuitive Surgical, Mountain View, CA) system are
      reviewed, as are simple mechanical-assist systems such as Omnitract (Minnesota
      Scientific, St. Paul, MN), Iron Intern (Automated Medical Products Corp., New
      York, NY), the Bookwalter retraction system (Codman , Somerville, NJ), the
      Surgassistant trade mark (Solos Endoscopy, Irvine, CA), the Trocar Sleeve
      Stabilizer (Richard Wolf Medical Instruments Corp., Rosemont, IL), and the
      Endoholder (Codman, Somerville, NJ).

PMID- 14642027
TI  - Conversion of an HM3 lithotripter into a research device.
AB  - PURPOSE: To describe the conversion of a Dornier HM3 lithotripter into a research
      device and evaluate its performance. MATERIALS AND METHODS: A used HM3
      lithotripter was donated to our university by the St. Thomas' Hospital in London.
      It was disassembled, shipped to our laboratory, partially assembled, and modified
      as a research lithotripter. Pressure measurements at several positions and kidney
      stone model fragmentation tests were performed to evaluate the modified system.
      Results were compared with information published by other authors and data
      obtained in our laboratory using another electrohydraulic research lithotripter.
      RESULTS: Pressure records showed typical lithotripter waveforms with a rapid rise
      to about 50 MPa, followed by decay to a negative peak of approximately 9 MPa.
      Maximum compressional peaks were obtained at F2 and 25 mm below F2. Kidney stone
      model fragmentation was typical for electrohydraulic shockwave lithotripters.
      CONCLUSIONS: Comparison of pressure measurements with data obtained by other
      authors on the same lithotripter several years ago indicate that the pressure
      waveform has not changed significantly. A much smaller water tank, a small X-Y-Z
      positioner, and no X-ray imaging system facilitate the use of this shockwave
      generator for in vitro experiments with small samples such as vials containing
      cell suspensions, having the advantage of a reliable, well-known, and well
      characterized commercial shockwave generator.

PMID- 14642028
TI  - Small-bowel perforation after shockwave lithotripsy.
AB  - A 51-year-old woman with a history of stone disease sustained two 3 x 2-mm ileal
      perforations during SWL (6000 shockwaves; 0.33-0.42 mJ/mm2) for a 14 x 8-mm left
      sided midureteral stone. Low energy levels should be applied when ureteral stones
      are treated by SWL with the patient prone.

PMID- 14642029
TI  - Management of ureteral stones with pneumatic lithotripsy: report of 500 patients.
AB  - PURPOSE: To evaluate the results of pneumatic lithotripsy (PL) with ureteroscopy
      in the treatment of ureteral stones. PATIENTS AND METHODS: We reviewed,
      retrospectively, the records of 500 patients (366 male, 134 female) with ureteral
      calculi treated by PL with the Swiss Lithoclast. Of these patients, 124 (24.8%)
      were treated primarily and 376 (75.2%) were treated secondarily after
      unsuccessful extracorporeal shockwave lithotripsy (SWL). The results were
      evaluated 3 months after treatment by excretory urography, ultrasonography, or
      both. RESULTS: The over-all stone-free and fragmentation rates were 94.6% and
      96.8%, respectively. These values were 97.1% and 98.5% for stones <or=10 mm and
      83.7% and 89.1% for stones >10 mm, respectively. The main complications were
      stone migration (2.0%), urosepsis (3.0%), and ureteral perforation (1.4%).
      CONCLUSIONS: While SWL is generally excepted as a first-line treatment option in
      ureteral stones because of its noninvasive nature, in situ lithotripsy, and
      especially PL, has higher success rates with minimal morbidity. Thus, PL seems to
      be a good alternative in patients in whom SWL was unsuccessful or not indicated
      and in patients who need early stone removal.

PMID- 14642030
TI  - Urinary stone size: comparison of abdominal plain radiography and noncontrast CT
      measurements.
AB  - BACKGROUND AND PURPOSE: To compare urinary stone size as measured by abdominal
      plain radiography (AXR) with stone size as measured by noncontrast three
      dimensional spiral CT in patients with acute renal colic. PATIENTS AND METHODS:
      Patients presenting to the emergency room of a single institution with urinary
      stones that were visible on both AXR and noncontrast spiral CT were identified.
      Two radiologists blinded to the clinical outcomes separately and randomly
      reviewed all films and measured maximum longitudinal (craniocaudal) and
      transverse (anteroposterior) stone diameters. The two-tailed paired Student's t
      test was used to compare the sizes of each stone on AXR and CT. RESULTS: Over a 1
      year period, 22 patients were identified with a total of 31 urinary stones
      visible on both AXR and CT. Nineteen stones were located in the kidney, three in
      the midureter, and nine in the distal ureter. The mean stone size by AXR was 6.1
      mm (range 2-13 mm; SD +/- 1.95) in the longitudinal axis and 5.3 mm (range 2-11
      mm; SD +/- 1.50) in the transverse axis. The mean stone size by CT was 6.9 mm
      (range 3-12 mm; SD +/- 1.95) in the longitudinal axis and 6.1 mm (range 2-11 mm;
      SD +/- 1.50) in the transverse. The differences between AXR and CT measurements
      did not attain significance in either the longitudinal (p = 0.67) or the
      transverse (p = 0.25) axis. CONCLUSIONS: A CT scan provides estimates of stone
      size that are consistently greater than those of AXR in both the longitudinal and
      transverse axes. However, for stones between 2 and 13 mm in maximum diameter,
      these differences do not attain significance. In patients with a history of
      radiopaque stones in this size range, therefore, AXR may provide useful size data
      for clinical decision-making without concern about significant disparities
      between the two modalities. As AXRs are more expeditiously obtained, incur less
      direct costs, and expose patients to significantly lower doses of radiation than
      CT scans, they remain a useful adjunctive study in the work-up of
      nephrolithiasis.

PMID- 14642031
TI  - Laparoscopy-assisted robotic radical cystoprostatectomy with ileal conduit
      urinary diversion for muscle-invasive bladder cancer: initial two cases.
AB  - BACKGROUND AND PURPOSE: The use of the da Vinci robot is being investigated in
      the discipline of urologic surgery. We describe our experience with its use
      during radical cystoprostatectomy in two patients with organ-confined bladder
      cancer. PATIENTS AND METHODS: Laparoscopic radical cystoprostatectomy with ileal
      conduit urinary diversion was performed using the da Vinci robot. Both patients
      were informed about this new approach, and informed consent was obtained.
      RESULTS: There were no intraoperative or postoperative complications. The
      operative time was 10 and 12 hours. A clear liquid diet was started on the third
      postoperative day. Final histopathology examination in both patients revealed
      T(3a)N(0)M(0) transitional-cell carcinoma. The hospital stay was 6 days. Both
      patients returned to normal activity within 2 weeks. CONCLUSION: Robot-assisted
      laparoscopic radical cystoprostatectomy with ileal conduit urinary diversion for
      muscle-invasive bladder cancer is feasible.

PMID- 14642032
TI  - Variables affecting deflection of a new third-generation flexible
      ureteropyeloscope (DUR-8 elite).
AB  - BACKGROUND AND PURPOSE: We performed an ex vivo study to measure the effects of
      various factors on the deflection angles of a new flexible ureteroscope with
      active primary and secondary deflections. MATERIALS AND METHODS: Active primary
      and secondary deflections in different sequences were measured initially without
      working devices (baseline measures). Nine different working instruments were then
      placed in the working channel, and alterations in ureteroscope deflectability
      were measured. RESULTS: Baseline measures showed excellent angles of deflections,
      consistent with the manufacturer's reporting. Among the wires tested, only the
      stiff wire had a negative (minor) impact on deflectability. There were similar
      minimal decreases of deflection with baskets. The 1.6F electrohydraulic
      lithotripsy (EHL) probe had minimal influence on deflectability compared with the
      3.0F EHL probe. The 200-microm and 365-microm laser fibers significantly (>20
      degrees ) decreased the angles of deflection. CONCLUSIONS: In spite of the
      changes in deflectability with almost all working instruments, there were no
      significant decreases in the angles with most of them. The sequence is important
      in obtaining optimal deflection.

PMID- 14642033
TI  - Controversial cases in endourology.

PMID- 14642034
TI  - Comparison of urinary stone and stent encrustation: biochemical analysis.
AB  - PURPOSE: To compare biochemical analysis of stent encrustation with that of
      urinary stones from the same patient. PATIENTS AND METHODS: Any patient
      presenting from February to December 2000 with a symptomatic ureteral or renal
      calculus that necessitated stenting and delayed calculus retrieval was enrolled
      in the study. The stent and stone were sent to the same laboratory for
      qualitative and semiquantitative chemical analysis. A total of 50 stents and
      matched calculi were available for comparison; four stents were excluded because
      they had insufficient encrustation for analysis. RESULTS: Two patients had open
      ureterolithotomy; the remainder were treated by endoscopic or percutaneous means.
      Every stone containing calcium oxalate had a stent that was positive for calcium
      oxalate. Four uric acid stones were available for comparison, and three of the
      four matched stents tested positive for uric acid. CONCLUSION: Biochemical
      analysis of urinary stent encrustation is a good predictor of urinary stone
      composition, especially for calcium oxalate-containing stones. Uric acid stent
      encrustation is likely to occur in patients with uric acid stones.

PMID- 14642035
TI  - Color Doppler ultrasonography in the diagnosis of vascular abnormalities
      associated with ureteropelvic junction obstruction.
AB  - PURPOSE: To determine if color Doppler ultrasonography is able to identify
      vascular abnormalities linked to ureteropelvic junction (UPJ) obstruction.
      PATIENTS AND METHODS: We used color Doppler scanning in 21 patients to determine
      whether there were aberrant vessels. RESULTS: The study detected 11 aberrant
      vessels, resulting in 10 true positives and 9 true negatives. Thus, the overall
      diagnostic accuracy was 90.4%. CONCLUSION: Color Doppler ultrasonography is
      reliable in the preoperative diagnosis of aberrant vessels associated with UPJ
      obstruction.

PMID- 14642036
TI  - Experience with laparoscopic splenectomy for ABO-incompatible living related
      renal transplantation.
AB  - PURPOSE: To determine whether laparoscopic splenectomy for ABO-incompatible
      living related renal transplantation is safe and effective. PATIENTS AND METHODS:
      From July 2000 to May 2002, laparoscopic splenectomy was performed on the day of
      transplantation in 10 patients undergoing ABO-incompatible living related renal
      transplantation. Perioperative and postoperative data, including operative time,
      blood loss, and complications, were evaluated. RESULTS: The mean operative time
      was 79 minutes. Intraoperative blood loss ranged from 25 mL to 600 mL (mean 130
      mL). Transfusion was not required in any case. One patient required open
      conversion because of bleeding from the splenic hilum. The serum amylase value
      was slightly elevated postoperatively in four patients but normalized with
      conservative treatment. One patient had bleeding from a trocar port wound, which
      was likewise treated conservatively. No complications, including postoperative
      renal dysfunction or fatal infections, that were considered attributable to the
      laparoscopic procedure were noted. CONCLUSIONS: Laparoscopic splenectomy
      performed simultaneously with renal transplantation is a safe and efficacious
      procedure for ABO-incompatible living related renal transplantation.

PMID- 14642037
TI  - Novel technique for diagnosis and management of Fraley's syndrome: helical CT
      with three-dimensional volume rendering.
AB  - We report on the diagnosis and minimally invasive management of Fraley's syndrome
      using helical CT with volume-rendering techniques in an 18-year-old patient.
      Three-dimensional images were generated rapidly and allowed safe planning and
      execution of a laser infundibulotomy of the upper-pole calix. After 24 months of
      follow-up, the patient remains pain free.

PMID- 14642038
TI  - Laparoscopic management of hydronephrosis in a woman with rare genitourinary
      anomalies: unicornous uterus, contralateral agenesis of the kidney, and
      contralateral ectopic ovary in the groin.
AB  - A 40-year-old woman had infected right-sided hydronephrosis and rare
      genitourinary anomalies-a dextroposed unicornous uterus-as the cause of the
      hydronephrosis, which had to be mobilized laparoscopically by dissecting the scar
      tissue. Furthermore, the patient had left-sided agenesis of the kidney and a left
      sided ectopic ovary with a rudimentary tube in the inner inguinal canal.

PMID- 14642039
TI  - Randomized, single-blind comparison of sidehole and end-hole v end-hole ureteral
      catheters.
AB  - BACKGROUND AND PURPOSE: Flexible 5F, open-ended ureteral catheters are currently
      available only with an end hole, which can lead to difficulties during retrograde
      pyelography and when aspirating urine for culture or cytology, as the hole
      frequently sucks up urothelium or debris and becomes occluded. We compared the
      traditional end-hole ureteral catheter with a catheter having a sidehole as well.
      PATIENTS AND METHODS: Twenty-two patients requiring aspiration of urine from the
      renal pelvis for cytology study or culture or to empty the collecting system
      during retrograde pyelography or prior to percutaneous nephrolithotomy were
      enrolled. Both end-hole-only and end-hole + sidehole catheters were employed in
      each patient, but the order of use was randomized, and the endourologist was
      blinded to the catheter type. Catheters were placed in the renal pelvis under
      fluoroscopy, and the renal collecting system was filled with 5 mL of contrast
      medium. The catheters were compared on volume aspirated initially, volume
      aspirated after repositioning, and ease of use judged on a three-item adjectival
      scale. RESULTS: The end-hole + sidehole catheters were able to aspirate more
      fluid initially (5.1 mL v 2.6 mL; P < 0.001) and after repositioning (6.0 mL v
      3.4 mL; P < 0.001). In addition, blinded urologists rated these catheters easier
      to use (12.0 v 3.0; maximum score 15; P < 0.001). CONCLUSIONS: The addition of a
      sidehole to ureteral catheters offers significant advantages to the endourologist
      seeking to aspirate urine from the upper collecting system for culture or
      cytology or during retrograde pyelography and in preparation for stone removal.
      The sidehole prevents occlusion of the catheter when it sucks up the urothelium
      and provides more efficient drainage of the upper tract.

PMID- 14642040
TI  - Retroperitoneoscopic nephropexy for symptomatic nephroptosis.
AB  - PURPOSE: Recently, laparoscopic nephropexy has been performed using a
      transperitoneal approach. We evaluated the efficacy of a retroperitoneoscopic
      technique for symptomatic nephroptosis. PATIENTS AND METHODS: Three men and two
      women with right nephroptosis underwent retroperitoneal laparoscopic nephropexy.
      Their symptoms were right flank pain, gross hematuria, or both. The mean body
      mass index was 18.7. Surgery consisted of complete dissection of the kidney,
      after which three sutures were placed between the renal capsule at the posterior
      lateral edge and the psoas or quadratus lumborum muscle. Silk sutures were used
      in all five patients. RESULTS: Retroperitoneoscopic nephropexy was successful
      with no intraoperative complications. The mean operative time was 167 minutes,
      and the mean estimated blood loss was <10 mL in all five patients. The mean
      convalescence period was 19.6 days. A postoperative urogram with the patients
      both supine and erect revealed an improvement in renal function, decreased
      displacement of the kidney (less than one vertebral body), or both. All patients
      were satisfied with the clinical outcome during an average of 18 months of follow
      up. CONCLUSIONS: Retroperitoneoscopic nephropexy is feasible for patients with
      symptomatic nephroptosis. We recommend nonabsorbable materials such as silk for
      fixation of the kidney to the psoas or quadratus lumborum muscle.

PMID- 14642041
TI  - Hand port-site metastasis of renal-cell carcinoma following hand-assisted
      laparoscopic radical nephrectomy: case report.
AB  - A 66-year-old man underwent hand-assisted laparoscopic radical nephrectomy (HALN)
      for a 10 x 7-cm, stage T(2)N(0)M(0) right-sided renal-cell carcinoma. Nine months
      later, tumor recurrence was noted at the previous hand port site. This is the
      first case report of such a metastasis. Possible mechanisms for tumor metastasis
      are reviewed, and preventive strategies are suggested.

PMID- 14642042
TI  - Management of adult Leydig-cell testicular tumors: assessing the role of
      laparoscopic retroperitoneal lymph node dissection.
AB  - BACKGROUND AND PURPOSE: Leydig-cell tumors represent <5% of malignant testicular
      tumors in adults. Orchiectomy is curative in approximately 90% of cases; however,
      the remaining men can develop metastases refractory to chemotherapy and
      radiation. We evaluated the role of laparoscopic retroperitoneal lymph node
      dissection (RPLND) in adult Leydig-cell tumors. PATIENTS AND METHODS: Between
      1999 and 2001, laparoscopic RPLND was performed with four transperitoneal ports
      within a unilateral template for six patients with pure Leydig-cell tumors.
      Presenting signs and symptoms, operative time, blood loss, intraoperative
      complications, postoperative complications, length of hospitalization, pathology
      reports, ejaculatory function, and survival were reviewed retrospectively.
      RESULTS: Laparoscopic RPLND was successful, without open conversions or
      reinterventions. Two vascular injuries occurred during dissection; additional
      intraoperative complications were not observed. Postoperatively, one patient
      developed erysipelas, but no other postoperative complications were recorded. The
      mean operative time was 190 minutes, and the mean length of hospitalization was
      4.3 days. Pathologic analysis of lymph nodes revealed no evidence of metastatic
      Leydig-cell tumor. At 12 months' mean follow-up (range 3-29 months), no
      recurrences have been identified. CONCLUSIONS: Laparoscopic RPLND is a safe,
      minimally invasive procedure for Leydig-cell tumors. Additional clinical
      experience is required to evaluate its effectiveness for pathologic stage II
      tumors and to determine if a therapeutic advantage can be realized with a
      protocol employing laparoscopic RPLND for adult Leydig-cell tumors.

PMID- 14642043
TI  - Laparoscopic ablation of giant renal cyst.
AB  - We report a case of a symptomatic giant (18 x 10 x 8-cm) renal cyst in a 40-year
      old woman that was marsupialized laparoscopically and excised. The surgical
      technique, based on progressive decompression of the cyst, is fully described.
      Excellent results were achieved. The recent application of laparoscopic ablation
      of different types of renal cysts is reviewed. This minimally invasive technique,
      when properly mastered, is highly effective and offers results similar to those
      of open surgery. It is associated with definitive postoperative advantages and is
      the treatment of choice for very large renal cysts, especially those located
      anteriorly, when sclerotherapy is ineffective or is contraindicated.

PMID- 14642044
TI  - Vattikuti Institute Prostatectomy: a single-team experience of 100 cases.
AB  - PURPOSE: To analyze the outcomes of the first 100 patients undergoing robotic
      radical prostatectomy by a single surgical team. PATIENTS AND METHODS: From
      August 2001 to May 2002, we performed robotic radical prostatectomy in 100
      patients with localized prostate cancer. The mean age was 60 +/- 0.67 years
      (SEM), the body mass index 27.5 +/- 0.35, the preoperative prostate specific
      antigen concentration 7.2 +/- 0.86 ng/mL, and follow-up 5.5 +/- 0.24 months.
      Thirty-eight patients also underwent pelvic lymph node dissection. We used the da
      Vinci surgical system and a subperitoneal approach (the Vattikuti Institute
      Prostatectomy; VIP). This is a prospective outcomes analysis of these patients.
      RESULTS: The mean operating time was 195 +/- 5.0 minutes, and the mean blood loss
      was 149 +/- 11.8 mL. No patient required blood transfusion. The stages of the
      cancers were pT(2a) in 21, pT(2b) in 64, pT(3a) in 5, pT(3b) in 9, and pT(3b)N(1)
      in 1. The positive surgical margin rate was 15%. At 1, 3, and 6 months, the
      continence rates were 37%, 72%, and 92%, respectively, and the potency rates were
      11%, 32%, and 59%. CONCLUSION: The VIP is a safe operation with excellent
      operative parameters, low morbidity, and good surgical margins. The early
      functional results are promising.

PMID- 14642045
TI  - Contact neodymium: YAG laser ablation of recurrent urethral strictures using a
      side-firing fiber.
AB  - PURPOSE: We evaluated the 2-year follow-up results of contact vaporization of
      recurrent urethral strictures using a side-firing Nd:YAG laser fiber. PATIENTS
      AND METHODS: A total of 21 male patients with recurrent benign urethral
      strictures 5 to 20 mm in length were treated with Nd:YAG laser in the contact
      mode using a side-firing probe. An initial urethrotomy was made at the 12 o'clock
      position by retrograde vaporization of the scarred tissue through the total
      length of the stricture with the aid of a metal guidewire. Then all the scarred
      tissue was gradually vaporized circumferentially until an adequate channel had
      been created and healthy normal tissue was visible. RESULTS: The mean operation
      time was 35 minutes (range 20-55 minutes). No significant bleeding or serious
      complication was seen in the perioperative or postoperative period. Hospital stay
      and catheterization time were 48 hours or less in all cases. The success rates at
      6, 12, and 24 months were 76%, 67%, and 52%, respectively. The morbidity of the
      laser treatment was minimal. CONCLUSIONS: The contact Nd:YAG laser is a safe
      treatment modality for recurrent urethral strictures. In view of the moderately
      durable successful results, it may be considered a last attempt at a minimally
      invasive treatment before making the decision for open urethroplasty.

PMID- 14642046
TI  - Advantages of transurethral rotoresection versus standard transurethral resection
      in the management of benign hyperplasia of the prostate.
AB  - BACKGROUND AND PURPOSE: The endourologic community is in search of safer and
      efficient alternatives to conventional transurethral resection of the prostate
      (TURP). This research compared the efficacy of two transurethral resection
      techniques - conventional loop and rotoresection - in the surgical management of
      benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From January 2000
      through December 2001, we randomized 128 BPH patients aged 55 to 74 years
      (average 61.4 +/- 2.7 years), all complaining of symptoms for prostatism for 1 to
      14 years (average 4.5 +/- 1.5 years), to either transurethral rotoresection
      (TURotor; N = 58) or TURP (N = 70). The mean ages in the two groups were 67.53 +/
      7.21 years and 62.93 +/- 6.43 years, respectively. The diagnosis of BPH was made
      on the basis of patient history, International Prostate Symptom Score (IPSS),
      digital rectal examination, transrectal ultrasonography, uroflowmetry, and serum
      prostate specific antigen (PSA) concentration. Three months after surgery, we
      again measured the residual urine volume, uroflow, IPSS, and prostate size by
      ultrasonography. RESULTS: The TURotor took 30.1 +/- 10.2 minutes with an
      intraoperative blood loss of 130 +/- 25 mL. During the immediate postoperative
      period, an insignificant amount of blood was visible in the urine and irrigation
      fluid. We removed the catheter at 1.8 +/- 0.69 days. At 3 months' follow-up, the
      maximum uroflow rate (Q(max)) had increased to 19.87 +/- 6.77 mL/sec, and the
      residual urine volume had fallen to 38.75 +/- 18.84 mL. The average TURP lasted
      42.1 +/- 13.2 minutes, or almost 30% longer than TURotor. The intraoperative
      blood loss averaged 21050 mL. The catheter was removed in 2.2 +/- 0.78 days. At 3
      months, the Q(max) was 20.78 +/- 6.56 mL/sec, and the average amount of residual
      urine had fallen to 35.48 +/- 8.71 mL. CONCLUSION: Rotoresection is a promising
      alternative to conventional TURP because it affords almost bloodless, 30% faster
      removal of prostate tissue.

PMID- 14642047
TI  - Use of fibrin glue and gelfoam to repair collecting system injuries in a porcine
      model: implications for the technique of laparoscopic partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: One of the challenges of laparoscopic partial
      nephrectomies is the repair of a collecting system injury. We hypothesized that
      fibrin glue plus Gelfoam could be sufficient to repair such injuries. MATERIALS
      AND METHODS: Four pigs (eight kidneys) underwent collecting system injuries of
      various lengths (3, 5, and 10 mm) (N = 8 each) during partial nephrectomy.
      Gelfoam soaked in the fibrin glue was applied to seal the collecting system and
      parenchymal defects. After 1 hour of passive filling, the renal pelvis was
      distended at supraphysiologic pressure to the point of leakage. Each repair site
      was examined for urinary extravasation during the physiologic and active phases
      of filling. RESULTS: Hemostasis was achieved, and all collecting system injuries,
      regardless of size, were free of urinary leakage at physiologic pressures.
      Moreover, all defects maintained a seal at supraphysiologic pressures of at least
      50 cm H(2)O. CONCLUSION: The combined use of fibrin glue and Gelfoam is an
      effective means to obtain hemostasis and seal collecting system injuries up to 10
      mm at physiologic pressures and up to 50 cm H(2)O in the acute setting. Our hope
      is that this technique can facilitate both laparoscopic and open partial
      nephrectomies. New technologies will be employed in an attempt to obtain better
      seating of the sealant plug in the future. Survival studies are in progress.

PMID- 14642048
TI  - Evaluation of heat shock protein 70 expression in renal parenchyma subjected to
      shockwave lithotripsy.
AB  - PURPOSE: In this experimental study in a rabbit model, renal parenchymal heat
      shock protein 70 (hsp70) levels were assessed in an attempt to evaluate the
      traumatic effects of high-energy shockwaves (HESW), which have been found to
      induce transient ischemia during the procedure. MATERIALS AND METHODS: Eighteen
      white New Zealand rabbits, each weighing 3 to 5 kg, were included in the study.
      The animals were divided into three groups, and various numbers of shockwaves
      (1000, 1500, or 2000) were applied to the same kidney of all animals under
      fluoroscopic localization with a Stonelith V5 lithotripter. Untreated
      contralateral kidneys were evaluated as controls. Following HESW application, the
      treated and untreated kidneys were removed surgically after 24 hours or 7 days.
      Tissue hsp70 levels were assessed by an immunohistochemistry method. RESULTS:
      During early follow-up (24 hours), both treated and untreated kidneys
      demonstrated moderate to severe hsp70 positivity. The number of positive tubules
      increased as the number of shockwaves increased, and positivity became more
      evident, possibly because of a higher degree of tissue damage. Contralateral
      kidneys demonstrated a limited degree of hsp70 positivity, although it was not as
      evident as in the treated kidneys. Assessment of tissue hsp70 levels during late
      follow-up (7 days) demonstrated moderate or limited degrees of positivity in the
      treated kidneys. Limited or no positivity could be demonstrated in the untreated
      kidneys during this period. CONCLUSIONS: Taking the known traumatic effects of
      HESW and the results of this study into account, the increasing positivity of
      hsp70 in parallel with the increasing number of shockwaves led us to think about
      a possible limited degree of ischemia induced by this procedure, as the traumatic
      effects of HESW were pronounced, as judged by tissue hsp70 positivity.

PMID- 14642049
TI  - Current status and perspective of diagnosis and treatment of thoracolumbar
      fracture in China.
AB  - Since the late 20th century owing to the improvement of spinal surgery
      techniques, the diagnosis and treatment of thoracolumbar fracture have been
      perfected more and more. Although the advent of modern spinal surgery in China
      was late, we have gained some advanced achievements owing to various
      international communications benefited from the open policy. Therefore, it is
      essential to evaluate the current status and perspective of diagnosis and
      treatment of thoracolumbar fracture. There are several issues we would like to
      discuss here.

PMID- 14642050
TI  - Therapeutic effect of nimodipine on experimental brain injury.
AB  - OBJECTIVE: To study the therapeutic effect of nimodipine on experimental brain
      injury. METHODS: Experimental and control rabbits were subjected to a closed head
      injury. In one group nimodipine was given intravenously and the effect evaluated
      by electron microscopy, brain water content, calcium levels, transcranial
      Doppler, and intracranial pressure monitoring. RESULTS: In rabbits treated with
      nimodipine the level of neuronal cytosolic free calcium was markedly decreased.
      There were less cellular damage and less spasm of the middle cerebral artery seen
      on electron microscopy. No difference regarding intracranial pressure changes
      between the two groups was noted. CONCLUSIONS: Nimodipine has a protective action
      on brain injury by blocking a series of pathological reactions induced by
      neuronal calcium overload, and by reducing the spasm of brain vessels and
      improving cerebral blood flow.

PMID- 14642051
TI  - Biomechanical study on the suture strength of ligament in cruciate ligament
      reconstruction.
AB  - OBJECTIVE: To test the suture strength on the tendon or ligament end and evaluate
      the stitch in the reconstruction of cruciate ligament and its clinical
      application. METHODS: Twenty-four specimens of patellar tendon with free ends
      were divided into 3 groups: Group I (3 Krackow stitches), Group II (2 Krackow
      stitches) and Group III (2 Krackow stitches with the first stitch passing through
      the tendon tissue as a modified Krackow stitch). These 3 groups were further
      divided into 6 subgroups according to different suture materials, No 1 Ethilon or
      stainless steel wire (phi=0.4 mm). Tensile test was undertaken to find out the
      least stitches with efficient suture pattern. RESULTS: Two Krackow locking
      stitches had stronger strength than 0.4 mm-diameter stainless steel wire. The
      fixation strength of 2 stitches with No 1 Ethilon was more than 80 N, superior to
      the failure strength of the material itself. The same strength was maintained if
      the first stitch was across the tendon tissue transversely. There was no
      statistically significant difference in the suture strength between 2 and 3
      Krackow locking stitches. CONCLUSIONS: The suture strength is greater than the
      failure strength of the suture material. Less suture exposure can be achieved
      when the first stitch is across the tendon tissue while maintaining a comparable
      strength to other sutures. To attain higher suture strength, stronger materials
      or multiple strands rather than more stitches are preferred. Therefore, a rapid
      early rehabilitation of range of motion (ROM) is possible and reliable in
      practice.

PMID- 14642052
TI  - Effect of nitric oxide synthase inhibitor on proteoglycan metabolism in repaired
      articular cartilage in rabbits.
AB  - OBJECTIVE: To study the effect of nitric oxide synthase inhibitor, S-methyl
      thiocarbamate (SMT), on proteoglycan metabolism in repaired articular cartilage
      in rabbits. METHODS: Twenty-four male New Zealand white rabbits, aged 8 months
      and weighing 2.5 kg+/-0.2 kg, were used in this study. Cartilage defects in full
      thickness were created on the intercondylar articular surface of bilateral femurs
      of all the rabbits. Then the rabbits were randomly divided into 3 groups (n=8 in
      each group). The defects in one group were filled with fibrin glue impregnated
      with recombinant human bone morphogenetic protein-2 (rhBMP-2, BMP group), in one
      group with fibrin glue impregnated with rhBMP-2 and hypodermic injection with SMT
      (SMT group) and in the other group with nothing (control group). All the animals
      were killed at one year postoperatively. The tissue sections were stained with
      safranine O-fast green and analyzed by Quantiment 500 system to determine the
      content of glycosaminoglycan through measuring the percentage of safranine O
      stained area, the thickness of cartilages and the mean gray scale (average stain
      intensity). Radiolabelled sodium sulphate (Na(2)(35)SO(4)) was used to assess the
      proteoglycan synthesis. RESULTS: At one year postoperatively, the percentage of
      safranine O-stained area, the mean gray scale and the cartilage thickness of the
      repaired tissues in SMT group were significantly higher than those of BMP group
      (P<0.01) and the control group (P<0.05). Result of incorporation of
      Na(2)(35)SO(4) showed that the proteoglycan synthesis in SMT group was higher
      than those of BMP group and the control group (P<0.01). CONCLUSIONS: SMT, a
      nitric oxide synthase inhibitor, can significantly increase the content of
      glycosaminoglycan and proteoglycan synthesis, and computer-based image analysis
      is a reliable method for evaluating proteoglycan metabolism.

PMID- 14642053
TI  - The in vitro myelin formation in neurospheres of human neural stem cells.
AB  - OBJECTIVE: To explore the culture conditions of human neural stem cells and to
      investigate the ultrastructure of neurospheres. METHODS: The cells from the
      embryonic human cortices were mechanically dissociated. N2 medium was adapted to
      culture and expand the cells. The cells were identified by immunocytochemistry
      and EM was applied to examine the ultrastructure of neurospheres. RESULTS: The
      neural stem cells from human embryonic brains were successfully cultured and
      formed typical neurospheres in suspension, and most of the cells expressed
      vimentin, which was a marker for neural progenitor cells, and the cells could
      differentiate into neurons, astrocytes and oligodendrocytes. In vitro myelin
      formation in neurospheres were observed at an early stage of culture.
      CONCLUSIONS: Human neural stem cells can be cultured from embryonic brains, can
      form the typical neurospheres in suspension in vitro and have the ability of
      myelinating, and may be potential source for transplantation in treating myelin
      disorders.

PMID- 14642054
TI  - Cerebral perfusion SPECT imaging for assessment of the effect of hyperbaric
      oxygen therapy on patients with postbrain injury neural status.
AB  - OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy on patients
      with postbrain injury neural status. METHODS: Two to 4 courses of HBO therapy
      and/or medications were used to treat 320 patients who were randomly divided into
      two groups. Assessment was made with (99m)Tc-ethyl cysteinate dimer ( (99m)Tc
      ECD) single photon emission computed tomography (SPECT) before and after
      treatment. RESULTS: There was a significant difference between the HBO therapy
      group and the non-HBO therapy group. HBO therapy was superior to medication
      treatment alone in the recovery of clinical symptoms, control of epilepsy, and
      resolution of hydrocephalus (P<0.01). CONCLUSIONS: HBO therapy has specific
      curative effects on patients with postbrain injury neural status, and (99m)Tc-ECD
      SPECT could play an important role in diagnosing postbrain injury neural status
      and monitoring the therapeutic effects of HBO.

PMID- 14642055
TI  - Effect of substance P on gene expression of transforming growth factor beta-1 and
      its receptors in rat's fibroblasts.
AB  - OBJECTIVE: To investigate the effect of substance P (SP) on gene expression of
      transforming growth factor beta-1 (TGFbeta-1), transforming growth factor
      receptor-1 (TGFR-1) and transforming growth factor receptor-2 (TGFR-2) in
      fibroblasts cultured in vitro from rat's granulation tissues. METHODS: The
      fibroblasts from the granulation tissues in the skeletal muscle of rat's hind
      limbs injured by formaldehyde were cultured in vitro. When different
      concentrations (10(-9)-10(-5) mol/L) of SP were added into the culture medium,
      the changes of gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the cultured
      fibroblasts were observed with reverse transcription polymerase chain reaction at
      different intervals (0, 3, 6, 12 and 24 hours after incubation). RESULTS: The
      gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts cultured from
      rat's granulation tissues was up-regulated by SP. The peak level of the mRNA
      expression was found at 10(-8) mol/L SP and the up-regulation effect was not
      found at 10(-5) mol/L and 10(-6) mol/L. The peak levels of gene expression of
      TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts treated with SP were achieved at
      6 and 12 hours, respectively. CONCLUSIONS: SP has up-regulation effect on the
      gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in fibroblasts from rat's
      granulation tissues in vitro, and the effect is related to different stimulating
      concentrations of SP. It may be concerned with proliferation and differentiation
      of fibroblasts and formation of scar tissues during wound healing.

PMID- 14642056
TI  - The analysis of epidemiological characteristics of road traffic crashes in a
      mountain city in western China.
AB  - OBJECTIVE: To study the epidemiological characteristics and preventive methods of
      road traffic crashes in a mountain city in western China through sampling
      investigation of traffic crashes in different regions of Chongqing city in recent
      years. METHODS: Two police teams of traffic management in downtown, two teams in
      suburb, one team in county and one freeway team were randomly selected, and road
      traffic crashes between 1988 and 1997 were investigated and analyzed. RESULTS: A
      total of 13121 road traffic crashes with 6201 crashes with casualties were
      analyzed. The incidence of crashes was higher in May, June and July, and on
      Friday and Wednesday and at 8:00-12:00 and 14:00-18:00 within a day. Casualties
      were 44.0% in pedestrians and 42.5% in passengers of total casualties. The deaths
      and severe injuries in pedestrians were 59.1% of total deaths and 56.4% of total
      severe injuries. The age of drivers and passengers were mainly at 18-30 years,
      followed by 31-40 years. People over 60 years old accounted for 24.1% of total
      pedestrian casualty. Head injury was the most common reason for deaths. The main
      reasons for these crashes were improper driving and violating traffic laws.
      Violating traffic laws by pedestrian was one of the main reasons for pedestrian
      casualty. CONCLUSIONS: The crashes are related to the characteristics of
      geography, climate, society activity of people, and the sense of traffic safety,
      the basic traffic construction and management in Chongqing. The traffic casualty
      of pedestrian is a big problem in Chongqing. To prevent and decrease road traffic
      injuries effective methods should be worked out and propaganda on traffic safety
      and traffic management should be strengthened according to different
      characteristics of different regions. To strengthen the first aid and treatment
      of cranium-brain injury and chest-back injury is also helpful in decreasing
      traffic deaths.

PMID- 14642057
TI  - Effect of methylprednisolone on reperfusion injury in severe uncontrolled
      hemorrhagic shock.
AB  - OBJECTIVE: To study the effect of methylprednisolone (MP) on reperfusion injury
      in severe uncontrolled hemorrhagic shock and explore the possible mechanism
      involved. METHODS: Twelve dogs were randomly divided into two groups, control
      group (Group I, n=6) and MP group (Group II, n=6). The animals were bled
      continuously from a femoral artery catheter to produce uncontrolled hemorrhagic
      shock models. Resuscitation with lactated Ringer's (LR) solution was initiated
      when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained
      at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when
      resuscitation began. While in Group I, normal saline (NS) was injected instead.
      The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured
      before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min
      (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output
      (CO) levels were recorded concomitantly. RESULTS: Infusion volume and hemorrhage
      volume shed from the superior mesenteric artery in Group I were higher than those
      in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased
      progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD
      levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise
      increase was present. At T(4), blood SOD level was significantly higher in Group
      II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower
      in Group II than in Group I. During reperfusion, MAP was more steady in Group II
      than in Group I and survival rate after 120 min (at T(4)) was higher in Group II
      than in Group I (P<0.05). CONCLUSIONS: MP has a protective effect on severe
      uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism
      mainly involves the anti-lipid peroxidation activity of MP.

PMID- 14642058
TI  - Effect of decoy-oligodeoxynucleotides on expression of inflammation mediators in
      pMPhi cells from rats.
AB  - OBJECTIVE: To study the effect of decoy-oligodeoxynucleotides (decoy-ODNs) in
      dumbbell shape with the oligodeoxynucleotide sequence similar to nuclear factor
      kappa B (NF-kappaB) cis-elements on expression of inflammation mediators in pMPhi
      cells from rats. METHODS: With carriers of cationic liposomes, decoy-ODNs were
      transfected into pMPhi cells of rats. Then the inhibiting effects of the decoy
      ODNs on tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and IL-10
      were analyzed. RESULTS: Decoy-ODNs could decrease the expression of TNFalpha and
      IL-6 in dose-dependent fashion but had weaker inhibiting effect on IL-10.
      CONCLUSIONS: Decoy-ODNs targeting NF-kappaB can decrease the expression of
      inflammatory mediators in pMPhi cells from rats.

PMID- 14642059
TI  - A correlative study between prevalence of chondromalacia patellae and sports
      injury in 4068 students.
AB  - OBJECTIVE: To study the prevalence of chondromalacia patella among college
      students and the correlation with sports injury. METHODS: 354 students from
      gymnastic department and 429 from nongymnastic department with knee joint pain
      were selected. 184 students from gymnastic department and 342 from nongymnastic
      department were checked randomly by a surgeon. 77 patients (37 males, 40 females)
      from gymnastic department and 119 patients (62 males, 57 females) from
      nongymnastic department were diagnosed as chondromalacia patellae. The amount of
      exercise and the occurrence of sports injury were investigated in each student.
      All data were analyzed with SPSS 10.0 statistical software. RESULTS: The
      prevalence of chondromalacia patella was 20.1% in female students and 11.6% in
      male students from gymnastic department, and 5.61% in female students and 4.92%
      in male students from nongymnastic department. The amount of exercise and the
      occurrence of sports injury to the knee joint in students from gymnastic
      department were greater than those from nongymnastic department. CONCLUSIONS: In
      both female and male students, the prevalence of chondromalacia patella is higher
      in gymnastic department than nongymnastic department. Sports injury is an
      important cause of chondromalacia patella.

PMID- 14642060
TI  - The diagnosis and treatment of severe cerebral fat embolism.
AB  - OBJECTIVE: To improve the diagnosis and treatment of severe cerebral fat embolism
      (SCFE). METHODS: The data of nine patients with SCFE were retrospectively
      analyzed. The manifestations of the central nerve system, respiratory system and
      hemorrhage were recorded, at the same time, accessory examination including
      arterial oxygen, fat macroglobules in venous blood and image examination was
      adapted. The patients were treated with exopexy, pharmocotherapy and
      oxygentherapy. RESULTS: Two of the nine patients died of severe complications,
      the other seven recovered without severe sequela. CONCLUSIONS: Gurd standard
      should be improved for early diagnosis of SCFE. If svere complications can be
      prevented, patients who receive early treatment will have favourable prognosis.

PMID- 14642061
TI  - Diagnosis and treatment of traumatic tricuspid valve insufficiency.
AB  - Traumatic tricuspid valve insufficiency (TTVI) is a relatively uncommon disease.
      To summarize the experience in the diagnosis and treatment of TTVI, we have
      analyzed the clinical data of 3 patients with TTVI who were admitted to the
      department of cardiac surgery of our hospital between April 1997 to April 2002.
      Relevant literatures have also been reviewed.

PMID- 14642062
TI  - Spontaneous diuresis and negative fluid balance predicting recovery and survival
      in patients with trauma-hemorragic shock.
AB  - Most patients with trauma-hemorragic shock, prior to ICU admission, have been
      resuscitated and stabilized in the emergency room (ER) and/or operation room
      (OR). Many of them suffer from systemic edema. This extra-vascular fluid is
      caused by massive infusion of fluid and blood for the maintenance of blood
      pressure. During the recovery stage, the patients exhibit spontaneous diuresis
      followed by negative fluid balance. Urine volumes of some patients are more than
      10000 ml/d. Do we need to maintain a balance between daily input and output of
      water at this situation? There are many references in the medical literature and
      textbooks about fluid resuscitation and the principles in maintaining the balance
      between input and output of water, but rarely about when and how to restrict it,
      that is, when and how to permit a negative balance. In this retrospective review,
      we examined the resuscitation records of 205 patients with systemic edema after
      trauma-hemorragic shock.

PMID- 14642063
TI  - [The relation between peripheral arterial occlusive disease and cardiovascular
      diseases in elderly population: a cross-section study in Wanshoulu area,
      Beijing].
AB  - OBJECTIVE: To investigate the prevalence of cardiovascular diseases (CVD) in the
      elderly with peripheral arterial occlusive disease (PAOD) and the prevalence of
      PAOD in the elderly with high cardiovascular factors. METHODS: A questionnaire
      survey was conducted, physical examination and electrocardiography were
      undertaken, blood pressure at the ankle artery and brachial artery was taken, and
      peripheral blood was drawn to determine the triglyceride, cholesterol, high
      density lipoprotein, low density lipoprotein, and fasting blood glucose among
      2,124 persons aged 60 approximately 95 (mean age 68.54 +/- 5.43), 943 males and
      1,183 females, in Wanshoulu area, Beijing. PAOD was defined as an ankle-arm index
      (AAI) < or = 0.9. RESULTS: (1) The prevalence rate of PAOD was 15.91% (16.42%
      after being standardized). (2) The prevalence rates of essential hypertension,
      hyperlipidemia, coronary heart disease, and diabetes mellitus in the elderly
      population with PAOD were 55.8%, 54.3%, 41.0%, and 25.4% respectively, among
      which the prevalence rates of hypertension, coronary heart disease, and diabetes
      were significantly higher in the population with PAOD than in the population
      without PAOD (P < 0.01, P < 0.05, and P < 0.05 respectively), The prevalence
      rates of hypertension in the female PAOD population and the prevalence rate of
      coronary heart disease in the male PAOD population were significantly higher than
      those in the populations without PAOD respectively (P < 0.001 and P < 0.01). The
      prevalence rate of CVD in the population with PAOD was 1.36 approximately 1.63
      times higher than that in the population without PAOD. (3) The prevalence rate of
      PAOD was 17.55% in the elderly population with single CVD risk factor (U =
      3.8661, P < 0.001), 20.33% in those with double risk factors, and 22.14% in those
      with triple factors (chi(2) = 7.240 8, P < 0.05) respectively. CONCLUSION: The
      prevalence of PAOD in Wanshoulu area is similar to that in the developed
      countries, suggesting that PAOD is also one of the common diseases in elderly
      population in China. The prevalence of CVD in the population with PAOD is
      significantly higher than that in the population without PAOD. The PAOD
      prevalence increases along with the increase of cardiovascular risk factors. PAOD
      in elderly population.

PMID- 14642064
TI  - [Genetic association of vitamin D receptor polymorphisms with primary biliary
      cirrhosis and autoimmune liver diseases on Chinese].
AB  - OBJECTIVE: To study the association between the polymorphisms of vitamin D
      receptor (VDR) gene and autoimmune liver diseases and (AIH) and primary biliary
      cirrhosis (PBC) in Chinese. METHODS: PCR-RELP was used to investigate the
      polymorphisms in exon 2, and exon 7 to exon 9 of VDR among 49 AIH patients, 58
      PBC patients, and 160 healthy controls, all Chinese. VDR polymorphisms were
      assessed by FokI, BsmI, ApaI, and TaqI endonucleases restriction fragment length
      polymorphism analysis after specific polymerase chain reaction (PCR)
      amplification. RESULTS: The distribution of VDR gene polymorphism in Chinese was
      similar to those in Koreans and Japanese, and different from those in the Germans
      and Spaniards. The percentage of ff phenotype carriers was significantly higher
      in the AIH patients than in the healthy controls (34.7% vs. 48.1%, chi(2) = 5.47,
      P = 0.019) and the percentage of Ff phenotype carriers was lower in the AIH
      patients than in the healthy controls (34.7% vs. 48.1%, P = 0.057). The
      percentage of Bb phenotype carriers was significantly lower in the PBC patients
      than in the healthy controls (5.2% vs. 17.5%, P = 0.021) and. the percentage of
      bb phenotype carriers was significantly higher in the PBC patients than in the
      healthy controls (94.8% vs. 80.6%, chi(2) = 6.52, P = 0.01). We also detected a
      significant association of the BsmI polymorphisms in PBC patients in comparison
      with controls (P = 0.01). Furthermore we found the difference in the FokI, BsmI,
      ApaI, and TaqI genotype distribution between Chinese health controls and
      Caucasian health controls. CONCLUSION: There is a significant association between
      FokI polymorphism and AIH and a significant association between the BsmI
      polymorphisms and PBC in Chinese.

PMID- 14642065
TI  - [Study on Calpain10 gene polymorphism in Chinese type 2 diabetes families].
AB  - OBJECTIVE: To detect the Calpain10 gene polymorphisms in North China families
      with type 2 diabetes and to investigate their association with type 2 diabetes.
      METHODS: PCR-RFLP method was used to test the polymorphisms of Calpain10 SNP43
      (G/A) and SNP19 (1/2) in 801 individuals from 218 type 2 diabetes mellitus (DM)
      families, 211 type 2 diabetes patients without family history, and 127 normal
      control subjects in northern China. RESULTS: (1) The Calpain 10 SNP43 "G" allele
      frequency was 91.9% in the type 2 diabetic patients without family history, 92.7%
      in the probands from the type 2 diabetes families without linkage between the
      onset of DM and SNP43 site, and 95.3% in the probands from type 2 diabetes
      families with linkage evidence at SNP43, all significantly higher than that in
      the controls (85.8%, chi(2) = 6.39, df = 1,P = 0.011; chi(2) = 8.437,df = 1, P <
      0.01); and chi(2) = 16.49, df = 1, P < 0.01). The distribution of polymorphism of
      the SNP19 site was not significantly different between the patients and control
      subjects. (2) Logistic regression analysis adjusted by BMI, sex and age showed
      that SNP43 G/G genotype was associated with type 2 diabetes. The odds ratios of
      the three group were OR = 1.78, P = 0.045; OR = 2.53, P = 0.008; OR = 4.32, P =
      0.000 respectively. CONCLUSION: SNP43 site of Calpain10 gene is related to type 2
      diabetes. Calpain 10 gene may be a related gene of type 2 diabetes in Chinese.

PMID- 14642066
TI  - [A novel keratin 17 gene mutation in a Chinese pedigree of delayed-onset
      pachyonychia congenita type II].
AB  - OBJECTIVE: To detect the keratin 17 gene mutation in a Chinese pedigree of
      typical delayed-onset pachyonychia congenita type II (PC-II) and to explore the
      relationship between the genetic mutation and the phenotype of PC-II. METHODS:
      The DNA was extracted from the blood samples of 19 patients with PC-II in four
      generations in the pedigree, 1 unaffected member of the pedigree, and 50 un
      related normal persons. Nested PCR was used to amplify the mutation hot spot in
      the exon 1 of keratin 17 gene. The PCR products were directly sequenced to detect
      the mutation. RESULTS: Sequencing of the PCR products revealed that the codon 109
      (AAC) was mutated as GAC in the nine affected members of the pedigree, causing
      the substitution of asparagine by aspartic acid in codon 109 (N109D) located in
      the 1A domain of keratin 17 gene. No such mutation was found in the unaffected
      member of the pedigree and the 50 unrelated controls. CONCLUSION: The novel
      missense mutation (N109D) located in the second half of 1A domain of keratin 17
      gene underlies the affected members' phenotype, delayed-onset pachyonychia
      congenita type II.

PMID- 14642067
TI  - [Analysis on GST-Pi genetic polymorphism in children with acute leukemia].
AB  - OBJECTIVES: To study the frequency distribution patterns of the genetic
      polymorphisms for glutathione S-transferase Pi (GST-Pi) in children with acute
      leukemia, and explore the possible relationship of GST-Pi gene mutation to the
      vulnerability of children with leukemia and the chemotherapeutic response.
      METHOD: Direct DNA sequencing was applied to detect the genotype polymorphism in
      85 healthy children as the control group and 120 children with acute leukemia.
      The distribution difference of the genotypes between them was analyzed. RESULTS:
      Gene mutation rate of GST-Pi exon5 was 47.5% in children with acute leukemia,
      significantly higher than that of 31.8% in the control group (OR = 1.944, 95% CI
      1.088-3.473), and this polymorphism distribution pattern was similar to that
      reported abroad. The mutation rate was much higher in ALL group than in others
      groups and was not significantly between the AML children and the control group.
      The overall mutation rate of B-lineage ALL (60.3%) was markedly higher than that
      of T-ALL (47.1%), but the homozygous mutation rate of the latter group (17.6%)
      was much higher than that of the former group (3.4%) (P < 0.05). The average
      survival time of the children with wild type exon5 was 24 months, longer than
      that of the mutation group (17.6 months), however with no statistical difference
      (P > 0.05). The genotype of exon5 had no effect on the survival time of AML
      children. No Ala(114)Val variant genotype of GST-Pi exon6 reported in literatures
      was found in this study, but two new mutant genotypes were discovered. A/G
      hybridity at 99 loci of exon6 was found in one healthy child and such hybrid
      genotype did not result in amino acid alteration. G-->T/G bases hybridity at 103
      loci of exon6 occurred in two children with leukemia, leading to GAC of Asp
      (aspartic acid) replaced by TAC of Try (tyrosine) at 147 loci of the protein
      peptide chain, producing Asp(147) Try hybrid mutation with a genotypic frequency
      of 1.7%. CONCLUSION: The gene mutation of GST-Pi exon5 is one of the potential
      vulnerable factors in leukemogenesis of the Chinese children and the genetic
      polymorphism of exon6 in Chinese is greatly different from that in other races.
      The role of the newly discovered variant genotype Asp(147) Try in leukemogenesis
      remains to be further studied.

PMID- 14642068
TI  - [Three-dimensional CT angiography with volume rendering for the detection of
      intracranial aneurysms].
AB  - OBJECTIVE: To evaluate the value of three-dimensional CT angiography (3D-CTA)
      with volume rendering (VR) for the detection of intracranial aneurysm. METHODS:
      Axial CT images were obtained by helical CT scanning on 45 patients with
      intracranial aneurysms, 15 males and 30 females, aged 63.9 (33-79 years). The
      primitive data were entered into the Silicon Graphics O2 board to be treated. VR
      technique was adopted to reconstruct 3D-CTA imaging, aided by multiplanar
      reformation to obtain the total volume of aneurysm. Among the 45 patients 25
      underwent DSA simultaneously, 21 underwent clamping of aneurysm, and 3 underwent
      GDC thrombosis. RESULTS: Fifty-nine intracranial aneurysms were detected in 45
      patients by 3D-CTA, including 32 small aneurysms (< or = 5 mm). 3D-CTA with VR
      well demonstrated aneurysms and provided useful information including the site,
      shape, size and spatial relationship to the surrounding vessels and bony
      structures. CONCLUSION: A quick, reliable, and relatively noninvasive diagnostic
      tool for intracranial aneurysms, 3D-CTA with VR delineates the aneurysmal
      morphology in detail, and provides useful information for choosing and planning
      microsurgical or endovascular treatment.

PMID- 14642069
TI  - [Preoperative etiological diagnosis of hemifacial spasm: a comparative study
      between magnetic resonance tomographic angiography and intra-operative findings].
AB  - OBJECTIVE: To summarize retrospectively the value of magnetic resonance
      tomographic angiography (MRTA) in the preoperative etiological diagnosis for
      hemifacial spasms (HFS). METHODS: 336 cases of HFS, 127 male and 209 female, aged
      46.2 (16-75), with a course of 1-29 years (6.2 years on average) and with the
      unilateral symptoms except one case were subjected to routine MRTA check up
      preoperatively. The MRTA findings were compared with the operative findings.
      RESULTS: Pre-operative evaluation by MRTA discerned 273 offending vessels with a
      positive rate of 81.3%, which were completely consistent with the intra-operative
      findings. The false positive and false negative rates were 8.0% and 9.8%
      respectively. Three cases of HFS due to secondary cause were found: one of CPA
      meningioma at the cerebellopontine angle and two cases of cholesteatoma.
      CONCLUSION: MRTA imaging provides more useful information concerning the etiology
      of hemifacial spasm than any other available diagnostic modalities. It is an
      effective and reliable means for pre-operative evaluation of the existence and
      sources of offending vessels in hemifacial spasm patients, and thus benefits the
      planning and guiding of intra-operative manipulation.

PMID- 14642070
TI  - [Epidemiologic study of admitted children with Kawasaki disease in Beijing from
      1995 to 1999].
AB  - OBJECTIVE: To evaluate the epidemiologic picture of Kawasaki disease (KD) in
      Beijing and its suburbs. METHODS: A questionnaire form and diagnostic guideline
      for KD were sent to all hospitals with pediatric inpatient beds throughout
      Beijing and its suburbs. Pediatricians were asked to review the medical records
      and report all patients with KD diagnosed during the 5-year period from January,
      1995, to December, 1999. RESULTS: A total of 710 patients with KD were reported
      from 37 (95%) of 39 hospitals with pediatric inpatient beds. The incidence rates
      of KD were 18.2 (1995), 21.1 (1996), 18.6 (1997), 30.6 (1998) and 27.8 (1999) per
      100,000 children < 5 years of age. The male:female ratio was 1.7:1. The age at
      onset ranged from 1 month to 13.4 years (with median of 2.3 years), with 85.2% <
      5 years old. The disease occurred more frequently in spring and summer and less
      frequently in autumn and early winter. Lymph node enlargement was the least
      common clinical sign, and its incidence decreased from 1995 to 1999. Cardiac
      abnormalities were found in 21.5% of patients and were more prevalent in patients
      diagnosed 10 days or longer after the onset. No patients died in the acute stage.
      CONCLUSIONS: The incidence of KD in Beijing is lower than that reported in Japan,
      similar to the incidence in the United States and higher than in those other
      Western countries. The age and gender distribution and increasing trend in
      incidence are similar to those in previous reports, but seasonal distribution is
      unique.

PMID- 14642071
TI  - [Prevalence of allergic respiratory disorders and skin prick test in Beijing
      urban and suburban children: a comparative study].
AB  - OBJECTIVE: To investigate the prevalence of allergic respiratory disorders and
      allergens in Beijing urban and suburban children. METHODS: Using the
      International Study of Asthma and Allergies in Childhood Phase III Protocol, a
      questionnaire survey was conducted among 7,077 junior middle school students,
      3,531 males and 3,546 females, aged 13-14, of 11 urban schools and 10 suburban
      schools in Beijing by random cluster sampling. Skin prick test with 13 common
      allergens was conducted among 2,126 from the 7,077 students by random cluster
      sampling. RESULTS: The prevalence rates of anamnestic asthma, asthma in recent 12
      months, asthma after exercise in recent 12 months, and dry cough during night in
      recent 12 months were 12.4%, 7.2%, 25.6%, and 19.3% respectively in the urban
      students; all significantly higher than those in the suburban students (4.5%,
      4.3%, 12.5%, and 8.3% respectively, all P < 0.01). The rates of anamnestic nasal
      symptoms without common cold, present nasal symptoms without common cold, and
      those nasal symptoms complicated with itching eyes and lacrimation were 41.6%,
      35.6%, and 10.3% respectively in urban students, and 21.3% all significantly
      higher than those in the suburban students (21.3%, 12.3%, and 3.3% respectively,
      all P < 0.05). The positive rates of the 13 main allergens were significantly
      higher in the urban students than in the suburban students (all P < 0.01). The
      positive rate of Dermatophagoides farinae and D. pteronyssinus, cat hair, and
      Blatella germanica were 20.4%, 16.9%, 10.8%, and 11.0% respectively in the urban
      students, all significantly higher than those in the suburban students (3.7%,
      2.7%, 3.7%, and 2.7% respectively, all P < 0.01). CONCLUSION: The prevalence
      rates of allergic disorders have been increased in comparison with those in the
      last decade in Beijing junior middle school students, especially those in the
      urban area and may be due to the changes of environments and living styles.

PMID- 14642072
TI  - [The correlation study of CT enhancement, intratumoral microvessel density and
      pathological grades in pancreatic carcinoma].
AB  - OBJECTIVE: The purpose of this work was to study the correlation of pancreatic
      phase CT enhancement, intratumoral microvessel density (MVD) and
      histopathological grades in pancreatic carcinoma and to evaluate the relationship
      between CT enhancement degree and the malignancy degree of pancreatic carcinoma.
      METHODS: 34 patients with pancreatic carcinoma underwent CT scanning before
      resection. The enhancement degrees and forms of tumor were observed in pancreatic
      phase. The operational sample was stained with HE and CD34 marked by
      immunohistochemistry. MVD and histopathological grades of pancreatic carcinoma
      were examined. CT enhancement of the tumor, MVD counting in hot spots areas of
      neoplastic parenchymal cells and pathological grades of pancreatic carcinoma were
      comparatively analyzed. RESULTS: Highly differentiated pancreatic adenocarcinoma
      was identified in 16 patients, moderately differentiated tumor in 7 and poorly
      differentiated tumor in 11. Isodensity CT enhancement was demonstrated in 13
      cases, slight low density enhancement in 9, slight low density enhancement along
      with small cyst lesion in 9 and slight low density enhancement along with large
      cyst lesion in 3. The counting of MVD with CD34 marked by immunohistochemistry in
      hot spot areas of neoplastic parenchyma cells were small in 10 cases, medium in
      16 and large in 8. The pathological grades correlated with CT enhancement of
      tumor (r = 0. 785 7, P < 0.001). The pathological grade correlated with MVD
      counting of tumor (r = 0.361 3, P < 0.05). The CT enhancement of tumor correlated
      with MVD (r = 0.676 8, P < 0.001). CONCLUSION: There was obvious and significant
      correlation between CT enhancement, pathological grades MVD numbers in the hot
      spot areas of tumor. The malignant degree of pancreatic carcinoma was inversely
      proportional to the extent of CT enhancement and inversely proportional to MVD
      numbers in the hot spot areas of tumor.

PMID- 14642073
TI  - [Myocardial protective effect of L-carnitine in cardioplegia solution on patients
      undergoing heart valve replacement operation].
AB  - OBJECTIVE: To investigate the myocardial protective effect of L-carnitine as an
      ingredient of cardiac arresting solution in the process of heart valve
      replacement operation. METHODS: 69 cases undergoing heart valve replacement with
      cardiopulmonary bypass (CPB), 47 males and 22 females, aged 48.17 +/- 14.22 (16
      approximately 74 years), were divided into 3 groups: test group I (n = 22, 12 g/L
      L-carnitine was put in the St. Thomas II cold crystal cardiac arresting liquid),
      test group II (n = 24, 6 g/L L-carnitine was put in the St. Thomas II cold
      crystal cardiac arresting liquid), and control group (n = 23, no L-carnitine was
      put in the St. Thomas II cold crystal cardiac arresting liquid). Before
      operation, 20 minutes after the beginning of shunt, after the finish of shunt,
      and 8 hours, one day, 3 days, and 7 days after operation venous blood was drawn
      to test the serum cardial tropnin I (cTnI), aspartate transaminase, lactate
      dehydrogenase, creatine kinase (CK) and CK-MB isozyme. Heart color
      ultrasonography was conducted to test the cardiac index (CI) and left heart
      ejecting fraction (EF) one day before operation and 7 days after operation.
      Before shunt and by the end of intracardiac procedure a bit of myocardial tissue
      was taken to undergo electron microscopy. The amounts of vaso-active drugs, such
      as dopamine and dobutamine, used postoperatively, and the postoperative cardiac
      auto-rebeating rate were recorded. RESULTS: The Amounts of vaso-active drugs used
      after operation was 329 +/- 54 mg in the test group I and 339 +/- 47 mg in the
      test group II, both significantly less than in the control group (669 +/- 56 mg,
      both P < 0.01) without a significant difference between the 2 test groups. Since
      the end of CPB to 3 days after operation, the serum levels of cTnI, aspartate
      transaminase, lactate dehydrogenase, CK and CK-MB isozyme were significantly
      lower in the 2 test groups than in the control group (P < 0.05 or P < 0.01). The
      serum level of cTnI in test group I was significantly lower than in the test
      group II (5.71 +/- 1.14 ng/ml vs 7.87 +/- 1.89 ng/ml 1 day postoperatively (P <
      0.05), and 5.01 +/- 0.89 ng/ml vs 7.53 +/- 1.43 ng/ml 3 days postoperatively (P <
      0.05). The postoperative cardiac auto-rebeating rate was 87.9% in the test group
      I and 74.3% in the test group II, both significantly higher than that in the
      control group (45.7%, P < 0.05 and P < 0.01). Heart color ultrasonogram showed
      that 7 days postoperatively the CI index was 2.86 +/- 0.55 and 2.74 +/- 0.56 in
      the 2 test groups, significantly higher than that in the control group (2.11 +/-
      0.35, both P < 0.05), and the left heart EF were 64.3 +/- 8.6 and 59.1 +/- 6.7 in
      the 2 test groups, both significantly higher than that in the control group (51.7
      +/- 4.9, both P < 0.05). Electron microscopy showed only slight swelling of
      mitochondria in the cardial cell and the myocardial fiber was intact by the end
      of operation in the 2 test groups without significant difference between these 2
      groups, however, in the control group swelling of mitochondria with vesicle
      formation, fissure of part of mitochondrial ridges, and disappearance of glycogen
      particles were found. CONCLUSION: Antegrade coronary perfusion of L-carnitine has
      a good protective effect on myocardium and is worth spreading for heart valve
      replacement patients with cardiopulmonary bypass.

PMID- 14642074
TI  - [Expression of estrogen sulfotransferase in breast tissues and the regulation of
      ESTmRNA by estrogen].
AB  - OBJECTIVE: To detect the expression of estrogen sulfotransferase (EST) in breast
      tissues, and to investigate its significance in breast carcinogenesis and the
      relationship between EST mRNA and estrogen. METHODS: Seven specimens of normal
      human breast tissues from patients with benign breast diseases were implanted
      subcutaneously into athymic nude mice, one specimen divided into many pieces to
      be implanted into 2 groups of mice, totalling 14 mice. Then the 14 mice were
      divided into 2 groups: as control and the other injected intramuscularly with
      estradiol benzoate (B-E(2)) every other day for 6 weeks. Six weeks after, the
      implanted tissues were taken out. Reverse transcription polymerase chain reaction
      (RT-PCR) was used to detect the expression of EST mRNA in 24 specimens of breast
      cancer, 6 specimens of normal breast tissues around the breast fibroadenoma, all
      resected during operation, and the specimens of implanted normal breast tissues
      from the mice (control group and B-E(2) group). The protein expression of
      estrogen receptor (ER) was detected by immunohistochemistry in the 24 specimens
      of breast cancer. RESULTS: EST mRNA was expressed in all normal human breast
      tissues and the expression was increased in the grafts from mice of B-E(2) group.
      However, the specimens of breast cancer showed decrease or absence of EST mRNA
      expression. CONCLUSION: EST mRNA expression is decreased or lost in breast cancer
      tissues. EST mRNA can be regulated by estrogen in normal breast tissues.

PMID- 14642075
TI  - [Suppression of HCT116 growth of cells by Gadd45].
AB  - OBJECTIVE: To study the mechanism of suppression of growth of HCT116 human colon
      carcinoma cells by Gadd45 gene. METHODS: HCT116 human colon carcinoma cells were
      transfected with pTRE-Gadd45 vector so as to establish Gadd45-inducible cell line
      that was cultured in medium with tetracycline. Then tetracycline was withdrawn.
      The number of cell clones was counted. Flow cytometry was used to detect the
      percentages of cells at the G1, S, and G2-M phases. TUNEL technique was used to
      detect the apoptosis of cells. Western blotting was used to analyze the
      expression of Gadd45 protein, and apoptosis-related proteins: poly-ADP-ribose
      polymerase (PARP), and caspase 3 protein. RESULTS: Gadd45 protein was not
      expressed in the HCT116 cells cultured in the medium with tetracycline, however,
      it was expressed with a gradually increased level in the cells cultured in the
      medium from which tetracycline was withdrawn, The clone formation rate of HCT116
      cells was 100% in the medium with tetracycline, however, was only 14.2% in the
      medium with tetracycline withdrawal, with a suppression rate of more than 85%.
      The percentage of cells in G(2)-M phase was significantly increased in the cells
      cultured in the medium with tetracycline withdrawal. 24-36 hours after the
      withdrawal of tetracycline, PARP and caspase 3 protein were activated remarkably.
      CONCLUSION: High expression of Gadd45 inhibits the growth of HCT116 cells,
      through inducing G2-M arrest and activating apoptotic pathway.

PMID- 14642076
TI  - [Production of aldosterone by rat mesangial cell and the accumulation of
      extracellular matrix induced by aldosterone].
AB  - OBJECTIVE: To investigate whether aldosterone (Aldo) may be synthesized by
      glomerular mesangial cells and whether Aldo promotes the synthesis of fibronectin
      (FN) and type IV collagen in mesangial cells. METHODS: Rat mesangial cells (RMC)
      were cultured and then divided into 4 groups: control group, AngII group (AngII
      of the concentrations of 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L was
      added), losartan group (AngII 1 type inhibitor losartan and AngII were added),
      and KCL group (KCL of the concentrations of 7 and 9 mmol/L was added). 48 hours
      after the RNAs of the cells in different groups were collected to detect the Aldo
      synthesized by the RMCs themselves. Another RMCs were cultured and divided into 4
      groups: control group, Aldo group (Aldo of the concentration of 10(-7) mol/L was
      added), spironolactone + Aldo group (spironolactone 10(-9) mol/L and Aldo 10(-7)
      mol/L were added), and spironolactone group (spironolactone 10(-9) mol/L was
      added). RT-PCR was used to detect the expression of the Aldo synthase CYP11B2,
      mineralocorticoid receptor (MR), and 11 beta-hydroxysteroid dehydrogenase (11
      beta-HSD2 (an enzyme required for MR ligand specificity) mRNAs and proteins. The
      level of Aldo in the incubation medium was detected by radioimmunoassay. After
      being exposed to 10(-7) mol/L Aldo for 24 h, the level of FN and type IV collagen
      in the incubation medium were examined by ELISA and Western blotting
      respectively. RESULTS: CYP11B2, MR, and 11 beta-HSD2 mRNA expressions were
      detectable in RMCs by RT-PCR and confirmed by sequencing. The concentration of
      Aldo in the incubation medium was 1.605 pg/10(6) cells. The mRNA expression of
      CYP11B2 was significantly up-regulated by both AngII and potassium.
      Immunocytochemistry showed that MR and 11 beta-HSD2 were distributed in both the
      cytoplasm and the nucleolus. After treatment of 10(-7) mol/L Aldo for 24 hours,
      the concentration of FN was 74 +/- 16 ng/ml, significantly higher than the
      baseline value (12.4 +/- 1.9 ng/ml, P < 0.05) and those of spironolactone group
      and spironolactone + Aldo groups (17.8 +/- 3.6 ng/ml and 25.9 +/- 5.3 ng/ml
      respectively); and the level of type IV collagen was 136% +/- 14%, significantly
      higher than the baseline level (100%, P < 0.05), and those of spironolactone
      group and spironolactone + Aldo groups (112% +/- 33% and 102% +/- 10%
      respectively). CONCLUSION: RMCs synthesize Aldo. Aldosterone also acts on RMCs,
      leading to extracellular matrix accumulation AngII and potassium are involved in
      the regulation of local production of aldosterone.

PMID- 14642077
TI  - [C3d molecular adjuvant increases the immunity of human chorionic gonadotropin
      beta DNA contraceptive vaccination and changes its immune response from Th1 to
      Th2].
AB  - OBJECTIVE: To testify the effect of C3d molecular adjuvant on the immunogenicity
      of human chorionic gonadotropin beta (hCG beta) DNA vaccination as well as the
      mode of immune response. METHODS: BALB/c mice aged 6 weeks were immunized
      intramuscularly two times at an interval of 3 weeks with by the plasmid pcDNA3
      (A1-3 groups), pcDNA3-hCG beta (B-3 groups), pcDNA3-hCG beta-C3d3 (C1-3 groups),
      or pCMV4-hCG beta-C3d3 (D1-3 groups), at dosage of 5 pmol, 10 pmol, and 20 pmol,
      respectively. Three weeks after the second vaccination the animals were killed,
      specimens of their peripheral blood were extracted to determine the anti-hCG beta
      antibody titer by indirect ELISA. Their spleen cells were harvested and
      stimulated in vitro by hCG antigen for 24 hours. The Th1/Th2 cytokines in the
      culture supernatant were determined by ELISA. RESULTS: At the dosage of 20 pmol,
      C3d molecular adjuvant significantly enhanced the anti-hCG beta antibody titer.
      The utmost anti-hCG beta antibody titer of C3 group was 1:450, 9 times higher
      than that of B3 group, and the utmost anti-hCG beta antibody titer of D3 group
      was 1:12 150, 243 times higher than that of B3 group. Stimulated in vitro by
      5,000 IU hCG beta antigen, the splenic cells of the C3 and D3 immunization group
      produced significantly lower IL-2, INF-gamma and TNF-alpha than those of the B3
      immunization group (P < 0.01 or P < 0.05). The IL-4 level of the C3 group was
      higher than that of the B3 group while the IL-10 level of the D3 group was
      significantly higher than that of the B3 group (P < 0.01). CONCLUSIONS: The C3d
      molecular adjuvant increases significantly the hCG beta immunogenicity of hCG
      beta DNA vaccination; meanwhile decreases the secretion of Th1 cytokines (IL-2,
      INF-gamma, and TNF-alpha), and increases the expression of Th2 cytokines (IL-4
      and IL-10) in response to hCG antigen. So C3d changes the anti-hCG immune
      response from Th1 type to Th2 type.

PMID- 14642078
TI  - [Detection of human papillomavirus type 16 E6 mRNA in carcinomas of upper
      digestive tract].
AB  - OBJECTIVE: To investigate the relationship between human papillomavirus (HPV)
      infection and the development of upper digestive tract carcinomas. METHODS: In
      situ hybridization (ISH) technique was used to detect the expression of HPV16 E6
      mRNA in 40 specimens of esophageal squamous cell carcinoma, 74 specimens of
      gastric cardiac adenocarcinoma, 40 specimens of adenocarcinoma of gastric corpus,
      62 specimens of adenocarcinoma of gastric antrum, all resected during operation,
      and 58 specimens of normal tissues of gastric mucosa, obtained by endoscopy.
      RESULTS: The positive rate of HPV16 E6 mRNA was 70% (28/40) in esophageal
      squamous cell carcinomas, 67.6% (50/74) in gastric cardiac adenocarcinomas, 47.5%
      (19/40) in adenocarcinoma of gastric corpus, 35.5% (22/62) in adenocarcinoma of
      gastric antrum, and 20% (10/50) in normal tissues of gastric mucosa respectively,
      without a significant difference between esophageal squamous cell carcinoma and
      gastric cardiac adenocarcinoma (P = 0.955). The positive rate in gastric
      adenocarcinoma was significantly lower than that in gastric cardiac
      adenocarcinoma (P < 0.05) or in esophageal squamous cell carcinomas (P < 0.01).
      The positive rate in normal tissue of gastric mucosa was significantly lower than
      those in gastric adenocarcinoma (P < 0.05) in gastric cardiac adenocarcinoma (P <
      0.01), and in esophageal squamous cell carcinoma (P < 0.01). The positive rate in
      gastric cardiac carcinomas was negatively correlated with TNM stage (P < 0.05).
      However, there was no correlation between HPV16 and gender, age, tumor size,
      depth of penetration, differentiation, lymph node metastasis, vascular invasion
      and prognosis of these patients with gastric cardiac carcinoma (all P > 0.05).
      CONCLUSION: HPV infects not only squamous epithelium, but also glandular
      epithelium. HPV16 may be an etiologic factor in the development of upper
      digestive tract carcinomas, especially esophageal and cardiac carcinomas.

PMID- 14642079
TI  - [The association of sulfotransferase1A1 His allele and breast cancer in Han
      ethnic Chinese women].
AB  - OBJECTIVE: To assess the relationship between SULT1A1 Arg213His polymorphism and
      breast cancer in Hans of Chinese women, as well as the interaction of the
      polymorphism and related risk factor of breast cancer. METHODS: Distribution of
      Arg213His polymorphism of the SULT1A1 gene was detected by using PCR-RFLP in 209
      cases of breast cancer and 426 matched healthy controls. The OR of susceptibility
      of SULT1A1 genotypes to breast cancer and the r value of interaction with
      exposure factors using multivariate logistic regression. RESULTS: (1) There was
      no significant difference in genotype of Arg/Arg, Arg/His and His/His of SULT1A1
      between case and control (P = 0.12). The frequency of His allele was 13.6% and
      9.5% in were determined case and control, respectively, P = 0.03; (2) Compared
      with Arg/Arg genotype, the risk of Arg/His and His/His was increased, P for trend
      = 0.04; The OR of His allele (Arg/His + His/His) was 2.60 (95% CI: 1.12 - 6.05, P
      = 0.04); (3) As for the interaction between gene and related exposure factors,
      His allele strengthen the effect of endogenous estrogen exposure (interaction
      index r > 1), and weaken the effect of factors related to exposure of some
      procarcinogen in dietary (r < 1), both being multiplicative interaction model.
      CONCLUSION: SULT1A1 His allele is positively associated with the risk of breast
      cancer, and an interaction exist between this allele and related exposure
      factors.

PMID- 14642080
TI  - [Analysis of anti-proliferation of curcumin on human breast cancer cells and its
      mechanism].
AB  - OBJECTIVE: To study the suppressive effects of curcumin on breast carcinoma cells
      and the mechanism. METHODS: Estrogen receptor (ER) positive human breast cancer
      line MCF-7 and ER negative human breast cancer line MDA-MB-231 were cultured 17
      beta estradiol and curcumin were added into the culture. Northern blot
      hybridization and Western blots were performed to detect the expression of mRNA
      and protein. The human ERE promoter activity was analyzed by transient
      transfection with CAT-reporter constructs. Invasion experiments were conducted
      with a Matrigel invasion chamber. RESULTS: Curcumin inhibit the proliferation in
      both estrogen receptor (ER) positive MCF-7 cells and ER negative MDA-MB-231
      cells. Curcumin's antiproliferative effects are estrogen dependent in ER positive
      MCF-7 cells. Curcumin inhibits the expression of ER downstream genes including
      pS2 and TGF-alpha (transforming growth factor-alpha) in ER-positive MCF-7 cells,
      and this inhibition is also dependent on the presence of estrogen. In addition,
      curcumin exerts strong anti-invasive effects in vitro which was not estrogen
      dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive
      effects appeared to be mediated through the down-regulation of MMP-2 (matrix
      metalloproteinase) and the up-regulation of TIMP-1 (tissue inhibitor of
      metalloproteinase). Curcumin inhibited the transcript levels of two major
      angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic
      fibroblast growth factor) in ER-negative MDA-MB-231 cells. CONCLUSION: Curcumin
      exerts multiple suppressive effects on breast carcinoma cells;it's mechanism of
      chemoprevention is pleiotropic.

PMID- 14642081
TI  - [The clinical significance of the expression of four cell cycle regulators in
      breast papillomotosis].
AB  - OBJECTIVE: To investigate the clinical significance of the protein expression of
      4 cell cycle regulators in papillomatosis of the breast. METHODS:
      Immunohistochemistry was used to examine the protein expression of CyclinD1, p16,
      E2F-1 and Rb in 4 groups (196 cases) with mild papillomatosis (MP), moderate
      papillomatosis (MoP), serious papillomatosis (SP) and ductal carcinoma in situ
      (DCIS). RESULTS: There were significant difference of the positive rate and the
      intensity of CyclinD1, p16, E2F-1 and Rb expression among the groups,
      respectively (chi(2) were 16.702, 20.742, 40.335, 42.317; 19.120, 29.469, 45.080,
      46.920, P < 0.01. Meaning time there were significant difference in the
      expression of these 4 factors between MoP and SP (P < 0.05). There was
      significance of E2F-1 or Rb expression between SP and DCIS (P < 0.01), but there
      was no significance to be found in the expression of CyclinD1 or p16 between the
      two groups (P > 0.05). Rb was screened as the highest risk factor by Odd Risk
      Logistic Analysis. CONCLUSION: CyclinD1, p16, E2F-1 and Rb played the important
      roles from MP into SP and then DCIS. E2F-1 and Rb can be used as the assistant
      indicators on the differentiation of SP and DCIS. Rb may be helpful in screening
      high risk cases from SP or MoP.

PMID- 14642082
TI  - [Association of herpes simplex virus type2 infection with dyslipidemia in
      Chinese].
AB  - OBJECTIVE: To investigate the relationship between herpes simplex virus type 2
      (HSV-2) infection and dyslipidemia. METHODS: ELISA was used to detect the
      specific IgG to HSV-2 in the samples of peripheral blood collected in succession
      from 1 244 inpatients, 408 with dyslipidemia and 836 controls without
      dyslipidemia. Univariate and multivariate analyses were preformed. RESULTS: No
      significant differences were found in sex and smoking status between the patients
      with and without dyslipidemia (both P > 0.05). However, the body mass index was
      significantly higher in the patients with dyslipidemia than in those without
      dyslipidemia (24.9 +/- 6.6 vs 23.9 +/- 7.6, P = 0.001). Diabetes and hypertension
      were more frequently found in patients with dyslipidemia in comparison with those
      without dyslipidemia (both P < 0.05). The prevalence of HSV-2 IgG seropositivity
      was significantly higher in the patients with dyslipidemia than those without
      dyslipidemia (38.2% vs 30.6%, P = 0.007). Binary Logistic regression analysis
      showed an association of HSV-2 IgG seropositivity with dyslipidemia, after
      adjustment for confoundings, the odds ratio for dyslipidemia was 1.34 (95%
      confidence interval, 1.04 to 1.72; P = 0.025) for HSV-2 IgG seropositivity. Other
      traditional risk factors, body mass index [adjusted OR 1.03 (1.01 - 1.05), P =
      0.002], hypertension [adjusted OR 1.39 (1.09 - 1.79), P = 0.008] and diabetes
      [adjusted OR 1.50 (1.05 - 2.15), P = 0.028]. CONCLUSION: HSV-2 infection is an
      independent risk factor for dyslipidemia, and HSV-2 infection may increase the
      risk of dyslipidemia.

PMID- 14642083
TI  - [Laboratory and clinical study of levofloxacin against Helicobacter pylori].
AB  - OBJECTIVE: To assess antibacterial activity of levofloxacin to Helicobacter
      pylori (Hp) strains In Vitro and In Vivo. METHODS: The Minimum inhibitory
      concentration (MIC) for 52 clinical isolates was detected by agar dilution method
      and was compared with those of amoxicillin and clarithromycin. To examine the
      effects of pH variation on the susceptibility of Hp to levofloxacin, Mueller
      Hinton agar with 7% defibrinated sheep blood was adjusted to a pH range of 4.0,
      5.0, 7.0 by adding hydrochloric acid. 85 Hp-positive Patients with chronic active
      gastritis or active peptic ulcer disease were consecutively recruited in a
      prospective, open-label study. The enrolled patients were randomised to receive a
      seven-day course of omeprazole 20 mg bid plus amoxicillin 1000mg bid and
      levofloxacin 200mg bid. Their Hp status was assessed by (13)C-urea breath test
      and/or endoscopy 4 - 6 weeks after the end of treatment. RESULTS: The resistant
      rates of strains to levofloxacin, amoxicillin and clarithromycin were 1.9%, 11.5%
      and 25%, respectively. A dual-resistance to amoxicillin and clarithromycin was
      demonstrated in five Hp strains (9.6%), which were all susceptible to
      levofloxacin. The prevalence of strains with resistance to levofloxacin was lower
      than that of strains with resistance to clarithromycin (P < 0.01), and was no
      statistically different with amoxicillin (P > 0.05). The activity of levofloxacin
      was diminished under acidic environment (P < 0.01). 84 enrolled patients
      completed the study. 76 patients (PP and ITT analysis, 91.7%; 90.6%) become Hp
      negative. Slight side-effects occurred in 5 patients (5.9%). CONCLUSION: In the
      present study, we report a high rate of resistance to amoxicillin and
      clarithromycin in this region. Omeprazole/levofloxacin-based triple therapy,
      including amoxicillin, is attractive because they combine a high eradication
      efficacy with an excellent tolerability and safety profile.

PMID- 14642084
TI  - [Association between polymorphisms in the microsomal epoxide hydrolase (mEH) gene
      and chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the association between polymorphisms in the microsomal
      epoxide hydrolase (mEH) gene and susceptibility to chronic obstructive pulmonary
      disease (COPD) in a Chinese population. METHODS: Polymerase chain reaction (PCR)
      and restriction fragment length polymorphism (RFLP) were performed to genotype
      mEH polymorphisms in exon3 (Tyr113-->His) and exon4 (His139-->Arg) in 100 COPD
      patients and 100 age and sex matched healthy controls. RESULTS: (1) The
      proportion of mEH heterozygotes in exon3 was significantly higher in the patients
      with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR)
      adjusted by age, sex, body mass index (BMI) and cigarettes years was 2.96 (95% CI
      1.24 - 7.09). (2) There was no marked difference in very slow activity genotype
      versus other genotypes between COPD patients and controls. (3) When COPD patients
      were nonsmokers, the OR of very slow activity genotype versus other genotypes was
      more than 1.00, and when COPD patients were smokers (Current smokers and ex
      smokers), the OR was less than 1.00. CONCLUSIONS: (1) mEH heterozygotes in exon3
      might be associated with the susceptibility to COPD in China. (2) The interaction
      might be existed between mEH genotype and smoke.

PMID- 14642085
TI  - [The risk factors of failed extubation after cardiac surgery in infants].
AB  - OBJECTIVE: To investigate the risk factors of failed extubation (FE) after
      cardiac surgery in infants. METHODS: 227 infants (< 1 year of age) who underwent
      congenital heart surgery in the period between January 2001 and December 2002
      were included in this study. Logistic regression analysis was used to assess the
      risk factors of failed extubation. Odds Ratio was used to suppose the degree of
      relationship between FE and risk factors. RESULTS: Out of the 227 infants
      undergoing congenital heart operations, 30 (13.22%) cases failed at the
      extubation. Risk factors for failed extubation included postoperative duration of
      ventilation (EOR = 12.0; 95% CI = 4.04 - 35.71; P = 0.000 9), postoperative
      pneumonia (EOR = 5.33; 95% CI = 1.81 - 15.68; P = 0.002) and preoperative
      pulmonary hypertension (EOR = 2.80; 95% CI = 1.21 - 10.45; P = 0.041).
      Postoperative pneumonia and preoperative pulmonary hypertension were the 2
      independent risk factors for failed extubation (P < 0.05). CONCLUSIONS:
      Postoperative pneumonia and preoperative pulmonary hypertension are major risk
      factors for failed extubation after congenital heart surgery in infants. To
      prevent and to treat postoperative pneumonia and pulmonary hypertensive crises
      will be beneficial to the successful extubation.

PMID- 14642086
TI  - [Eosinophilic cystitis in children:a report of six cases and review of
      literature].
AB  - OBJECTIVE: Eosinophilic cystitis is a very rare tumor-like inflammatory disease
      especially in children. It can involve any portion of the bladder and interfere
      with its function. Here we present 6 pediatric cases and review the literature.
      METHODS: Six children, with mean age of 8.3 years, were referred to our clinic.
      Their major complaints included voiding urgency, frequency, dysuria, enuresis,
      intermittent hematuria and abdominal pain. Ultrasound, CT scan and voiding
      cystourethrogram (VCUG) showed diffuse thickening of bladder wall and a filling
      defect lesion. They all suggested the possibility of bladder tumor. The final
      diagnosis of eosinophilic cystitis was made by cystoscopic tissue biopsy or open
      surgery. Patients underwent bladder autoaugmentation, mass resection or mere oral
      administration of corticosteroid and antibiotics respectively. RESULTS: 5 among 6
      patients were followed up for 5 - 28 months. Their voiding complaints and image
      changes gradually disappeared. Up to now, there is no relapse. CONCLUSIONS: The
      clinical presentation of eosinophilic cystitis includes irritative voiding
      symptoms, hematuria and abdominal pain. Tumor-like changes could be found in the
      imagination examinations. A biopsy is mandatory to establish the diagnosis.
      Treatment in general varies from the removal of the antigenic stimulus, if
      identifiable, to administration of corticosteroid and antibiotics. When patients
      fail to respond to the medication treatment, the opening operation could be
      required.

PMID- 14642087
TI  - [Study of cooperation of tumor suppressor p33(ING1b) with p53 gene in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the cooperation effect of p33(ING1b), coded protein of
      the novel tumor-suppressor gene ING1b, with p53 gene on the cell growth, cell
      cycle arrest, apoptosis and expression of the p53 downstream gene p21(WAF1/CIP1)
      in hepatocellular carcinoma. METHODS: Recombinant plasmids pcDNA3-INGIb
      containing sense p33(ING1b) cDNA, and pCMV-wtp53 containing sense p53 gene, and
      were transfected into HepG2, PLC/PRF/5 and Hep3B hepatoma cell lines with
      different p53 endogenous expression status using lipofecTAMINE method.
      Recombinant plasmids pcDNA3-alphaING1b containing antisense p33(ING1b) cDNA, pCMV
      alphawtp53 containing antisense p53 gene, and plain vector as control were
      transfected into the cells. Forty-eight hours after transfection, the apoptosis
      rates were detected and cell cycle arrest were analyzed by flow cytometry. The
      expression of p33(ING1b) and wtp53 proteins were detected by Western blot. The
      luciferase gene reporter plasmid drived by p21(WAF1/CIP1) promoter was also
      transfected into the cells to analyze the activation of p21(WAF1/CIP1) gene in
      hepatoma cells. Then 6% ethanol was added into the in DMEM culture medium and all
      of the above experiments were repeated. RESULTS: After the p33(ING1b) gene was
      transfected, the apoptosis rate of HepG2 cells which express endogenous wtp53 was
      enhanced (22.53%), the number of cells arrested in G(0)/G(1) phase was increased
      (67.45%), and the activation of p21(WAF1/CIP1) promoter reached the highest level
      (13.08) (all P < 0.01). In the PLC/PRF/5 cells which express endogenous mutant
      p53, after combined p33(ING1b) and wtp53 gene transfection the percentage of
      cells arrested in G(0)/G(1) phase (78.16%) and the activation of p21(WAF1/CIP1)
      promoter (12.99) were higher than those in the experiment groups transfected with
      p33(ING1b) or wtp53 gene alone (both P < 0.01), however, the difference in
      apoptosis rate was not statistically significant (P > 0.05). After 6% ethanol
      treatment, apoptosis rate of PLC/PRF/5 cells transfected with combined p33(ING1b)
      and wtp53 gene was increased significantly (42.8%). The apoptosis rate and cell
      cycle arrest were not significantly different between the Hep3B cells with
      deletion of wtp53 which were transfected with p33(ING1b) and wtp53 gene and those
      of the control group (P > 0.05), however, the activity of the p21(WAF1/CIP1)
      promoter was activated in the combined transfectlion group (10.32, P < 0.01).
      CONCLUSION: p33(ING1b) cooperate with wtp53 in the process of inhibiting hepatoma
      cell growth, inducing apoptosis, and activating p53 downstream gene
      p21(WAF1/CIP1), and after chemical inducing reagent treatment the cooperation
      between p33(ING1b) and wtp53 gene is enhanced.

PMID- 14642088
TI  - [p120(ctn) tyrosine phosphorylation are involved in the biologic behavior changes
      of hepatocellular carcinoma cells].
AB  - OBJECTIVE: In hepatocellular carcinoma cells, the tyrosine phosphorylation of
      p120(ctn) was stimulated by epidermal growth factor (EGF) to investigate the
      relationship between the tyrosine phosphorylation of p120(ctn) and the
      translocation of p120(ctn), also the relationship between the tyrosine
      phosphorylation of p120(ctn) and the biological behaviour of hepatocellular
      carcinoma cells. The role of p120(ctn) in the cell adhesion and signaling of
      hepatocellular carcinoma is to be investigated. METHODS: In BEL-7404 human
      hepatocellular carcinoma cells, the tyrosine phosphotyrosine of p120(ctn)
      stimulated by EGF were detected by immunoprecipitation (IP) and Immunoblotting
      (IB). The cellular distribution and translocation of p120(ctn) and beta-catenin
      were detected and examined by indirect intracellular immunofluorescence. Cell
      morphology and cell adhesion potential were also detected using correspondent
      methods. Antisense nucleotide of p120(ctn) was transfected into BEL-7404 cells.
      RESULTS: The tyrosine phosphorylation of p120(ctn) was enhanced after EGF
      treatment than control, especially at 20min after EGF treatment; When BEL-7404
      cells were transfected with antiseuse nucleotide of p120(ctn) before EGF
      treatment, the tyrosine phosphorylation of p120(ctn) stimulated by EGF was
      obviously lowered. We also observed that the tyrosine phosphorylation of
      p120(ctn) stimulated by EGF was accompanied by the nuclear translocation of
      p120(ctn); the similar translocation was also observed in beta-catenin after EGF
      stimulation. At the meantime, cell adhesion potential was reduced after EGF
      treatment and cell morphology became thin, elongated and irregular, speudopods
      increased. CONCLUSIONS: In BEL-7404 cells,the tyrosine phosphorylation of
      p120(ctn) could be stimulated by EGF, which was accompanied by the nuclear
      accumulation of p120(ctn). The tyrosine phosphorylation of p120(ctn) stimulated
      by EGF was also in correlation with the changes of cell adhesion and cell
      morphology. The results indicated that the tyrosine phosphorylation of p120(ctn)
      cell correlated with the translocation of p120(ctn) and the biological behavior
      of cells.

PMID- 14642089
TI  - [Functional significance of CD40 and CD40 ligand linking on human lung cells].
AB  - OBJECTIVE: To determine the possible functional significance of CD40 and CD40
      ligand (CD154) linking on human lung carcinomas and to assess the potential of
      CD40 as a therapeutic target. METHODS: We evaluated the effect of CD40L on the
      surface expression of major histocompatibility complex class I (MHC-I), Fas,
      bcl2, CD54, epidermal growth factor receptor (EGFR), p-glucoprotein (PGP), lung
      related protein (LRP), cell cycle, cell apoptosis and growth kinetics of 7 lung
      cancer cell lines (including 1 CD40-transfected cell line GLC-82/CD40) by gene
      cloning, Western blotting, and flow cytometry etc. RESULTS: Significant increased
      expression of MHC-I, CD54 and Fas was observed in 4 tumor lines expressing high
      levels of CD40 after CD40L (0.1 micro g/ml) linked to CD40. CD40L (0.1 micro g/ml
      or greater) in the fifth day was found to significantly inhibit the proliferation
      of 4 cell lines expressing high levels of CD40, decreased the percentage of
      aneuploid cell, and inhibited S-phase cells entering G2/M phase. The effect of
      CD40 cross-linking was reversible. CD40-moderate and low and negative tumor did
      not respond to CD40L. All of 7 cell lines show no significant changes in
      apoptosis in either the experimental (CD40L pulsed) or control (medium only) cell
      cultures. CONCLUSION: Expression of CD40 on lung tumors cells expressing high
      level of CD40 (including CD40-transfected cells) may represent a potential
      therapeutic target.

PMID- 14642090
TI  - [Mechanism of the mitogen-activated protein kinase phosphatase-5 regulating the
      growth and invasion of a human prostate cancer cell line].
AB  - OBJECTIVE: To investigate the effects of mitogen-activated protein kinase
      phosphatase-5 (MKP5) on the biological behaviors of cell and the activation of
      mitogen-activated protein kinase (MAPK) induced by P2Y purinergic receptor
      agonist ATP in the prostate cancer cell line 1E8. METHODS: 1E8 cells were
      cultured. The recombinant plasmid pcDL-SRalpha296-MKP5 containing the human wild
      type MKP5 cDNA and blank vector pcDL-SRalpha were co-transfected with pcDNA3
      vector plasmid into the 1E8 cells respectively to get strong expression clones.
      RT-PCR was used to detect the expression of MKP5 mRNA. ATP, MEK inhibitor PD
      98059, and p38 inhibitor SB 203580 were added into the culture. Then the total
      protein was extracted, SDS-PAGE and Western blotting were used to detect the
      activation of p38 and ERK1/2 induced by ATP with phosphospecific antibodies
      directed against the dually phosphorylated, active forms of p38 and ERK1/2. The
      in vitro growth curve was drawn, soft agar colony formation test was made, and
      Matrigel membrane-penetrating experiment was made to test the invasion ability of
      1E8 cells. RESULTS: The activity of p38 and that of ERK1/2 of the 1E8 cells
      untreated by ATP were almost undetected. ATP time-dependently stimulated the
      activities of ERK1/2 and p38 kinases, inhibited the in vitro growth and colony
      formation on soft agar, and promoted the in vitro invasion of 1E8 cells. MKP5
      transfection effectively inhibited the p38 activity induced by ATP and blocked
      the effects by ATP stimulation on 1E8 cells. The activity of p38 kinase was
      significantly decreased both in the control and MKP5 transfected cells that were
      pretreated with SB203580 and then with ATP with an inhibition rates of 83.14% and
      58.00% (P < 0.001 and P = 0.003). The growth of cells transfected with MKP5 was
      significantly inhibited (P < 0.001) and further inhibited by addition of ATP. The
      inhibition of growth of MKP5-transfected cells by ATP could be partially reversed
      by pretreatment of PD98059 (P < 0.05). The number of cells transfected with MKP5
      that penetrated the membrane was significantly less than that of the control
      cells (P = 0.000 9). ATP increased the penetrating ability of different cells
      (all P < 0.01), and this action was partially inhibited by MKP5 transfection and
      addition of SB203580 (P < 0.001), but not by the addition of PD98059. ATP
      treatment decreased the colony formation on soft agar of different cells,
      especially of the MKP5 transfected cells (P < 0.001). Such action was partially
      reversed by SB203580 and PD98059. CONCLUSION: The p38 and ERK1/2 pathways exert
      different effects on the in vitro growth, invasion and colony formation of 1E8
      prostate cancer cells related to ATP. The p38 pathway may be more important in
      the invasive capability of 1E8 cells. MKP5 plays an important role in the
      regulation of p38 action.

PMID- 14642091
TI  - [Transplantation of fetal cardiomyocyte regenerates infarcted myocardium in
      rats].
AB  - OBJECTIVE: To investigate the feasibility and efficiency of fetal cardiomyocyte
      transplantation into the rat model of myocardial infarction. METHODS:
      Cardiomyocytes were isolated from aborted human embryos aged 12 - 16 weeks and
      cultured for 5 days to confirm their viability. Rat model of extensive myocardial
      infarction (MI) was established in 18 male Wistar rats by ligating the descending
      anterior branch of left coronary artery and the 18 rats were randomly divided
      into 2 groups: transplantation group (n = 7, 2 x 10(6) fetal cardiomyocytes were
      transplanted into the myocardial scar) and culture medium injection group (n = 6,
      culture medium was injected into the myocardial scar) 5 days after extensive MI
      was caused. Another 6 rats undergoing sham operation were used as controls.
      Echocardiography was performed before and 60 +/- 3 days after the implantation to
      assess the left ventricular (LV) remodeling and cardiac function. Then the rats
      were killed and their heart were harvested to undergo HE staining,
      immunohistochemical examination with antibody against human alpha-actin smooth
      muscle (SMA) isoform, and light microscopy. RESULTS: Light microscopy revealed
      the presence of engrafted human fetal cardiomyocytes in the infarcted myocardium
      and the presence of nascent intercalated disks connecting the engrafted fetal
      cardiomyocytes and the host myocardium. The engrafted fetal cardiomyocytes were
      SMA positive. Serial echocardiography revealed that cell transplantation
      prevented scar thinning, LV further dilatation and dysfunction while the control
      animals developed scar thinning, significant LV dilatation accompanied by
      progressive deterioration in LV contractility. CONCLUSION: Fetal cardiomyocytes
      can be implanted and survive in the infarcted myocardial cells, thus preventing
      the scar thinning, and LV further dilatation and dysfunction.

PMID- 14642092
TI  - [Effects of aldosterone and spironolactone on the proliferation and collagen
      synthesis of hepatic stellate cells in rats].
AB  - OBJECTIVE: To investigate the effects of aldosterone and spironolactone on the
      proliferation and collagen synthesis of hepatic stellate cells. METHODS: Rat HSC
      were incubated with aldosterone or spironolactone, an aldosterone receptor
      antagonist at different concentrations. The proliferation of HSC was measured by
      (3)H-thymidine incorporation, and the collagen synthesis by (3)H-Proline. The
      changes of HSC cycle were analyzed by FCM. RESULTS: At dose of 10(-4) mol/L, ALD
      increased the incorporation of (3)H-TdR and (3)H-Pro (P < 0.05), but didn't at
      the lower doses. Spironolactone significantly inhibited HSC proliferation and
      collagen synthesis. The effective concentration was among 10(-4) mol/L - 10(-6)
      mol/L, and in dose-dependent manner. The percentage of G(1) phase of the cell
      cycle was significantly increased, and the cell proliferation suppression of
      spironolactone is associated with cell arrest in G(1) phase. Co-stimulation with
      aldosterone and spironolactone did not have significant effects on HSC
      proliferation and collagen synthesis compared with the control group. CONCLUSION:
      The proliferation and collagen synthesis of HSC might be enhanced by ALD at
      higher concentration, but was inhibited by spironolactone.

PMID- 14642093
TI  - [The observation of bone mineral density by dual energy X-ray absorptiometry and
      histology during fracture healing at the femoral fracture site of rat].
AB  - OBJECTIVE: To dynamically observe the bone mineral density and histology changes
      during fracture healing at the femoral fracture site, and to study the role of
      monitoring fracture healing by dual energy X-ray absorptiometry (DEXA). METHODS:
      60 female 3-month-old SD rats were used to establish right femoral fracture
      model. The fractured and contralateral unfractured femorals were scanned by Dual
      Energy X-ray absorptiometry in 2, 4, 6, 8, 10 and 12 weeks postoperatively. The
      callus of each rat was examined by light microscope at the same time. RESULTS:
      The value of bone mineral density at rat femoral fracture site was significantly
      increased post-osteotomy, showing a clear healing trend. The bone mineral density
      at fracture site was 29.5%, 48.3%, 85.3%, 105.2% of the value obtained of the
      control limb 2, 4, 6 and 8 weeks postoperatively. There was a compatibility on
      time between bone mineral density and histology. The BMD of distal metaphysis
      remained reduced until 12 weeks. CONCLUSION: The change of bone mineral density
      at the fracture site exhibited positive correlation with the histology of
      fracture healing, bone mineral density can accurately quantify the extent of
      mineralization of callus at the fracture site. DEXA can be used as a new
      technique in monitoring fracture healing.

PMID- 14642094
TI  - [The role and significance of retrohepatic tunnel and the liver hanging tape
      passed through the tunnel in difficult hepatectomies].
AB  - OBJECTIVE: To explore the role and significance of liver hanging tape passed
      through the retrohepatic tunnel developed by dissecting the tissue plane between
      anterior surface of the inferior vena cava (IVC) and caudate lobe, in order to be
      substitute for control of in- and out-flow blood vessels in difficult
      hepatectomies. METHODS: Retrohepatic tunnel was developed by dissecting the
      anterior surface of the retrohepatic portion of the IVC, 7 difficult
      hepatectomies were performed with the use of liver hanging tape and hemostatic
      plate. RESULTS: Liver hanging tape was placed successfully in 7 cases. VIII
      segmentectomy, right hemihepatectomy, left hemihepatectomy and right trilobectomy
      plus complete caudate lobectomy were performed, there was no complication related
      to this maneuver. CONCLUSION: It is feasible for placing liver hanging tape
      through the retrohepatic tunnel. In addition, it has extensive indications and
      minimal influence on hemodynamic response. It is a better way for the difficult
      hepatectomy and for harvesting the liver graft in living related liver
      transplantation.

PMID- 14642095
TI  - [The variation of T-cell clonal repertoire in patients with systemic lupus
      erythematosus (SLE) following autologous peripheral blood hematopoietic stem cell
      transplantation].
AB  - OBJECTIVE: Analyze the variation of T cell receptor(beta) (TCRbeta) CDR3 gene
      expressing repertoire in systemic lupus erythematosus (SLE) patients before and
      after autologous peripheral blood hematopoietic stem cell transplantation
      (APBSCT), to search the pathogenesis of SLE and characteristics of T cell
      reconstitute immune after APBSCT. METHODS: Reverse transcriptase - polymerase
      chain reaction (RT-PCR) amplified 25 subfamily genes of TCRbeta prom peripheral
      blood lymphocytes (PBLs) of SLE patient with APBSCT and run denaturation
      polyacrylamide sequencing gel electrophoresis, set up a map of TCRbetaCDR3 gene
      expressing repertoire. The bands of TCRbeta gene repertoire in the
      electrophoresis gel can be used to analyze the variety of T cell clones which
      expanded and disappeared in cases of SLE. Cut the bands and sequencing. Compare
      sequences of TCRbetagenes in normal and abnormal T cell clones to understand the
      relationship between TCRbeta gene and autoimmune diseases. RESULTS: In the normal
      control group, TCRbeta gene repertoires show more than 10 bands in each of 25
      TCRbetaV families, characterized as Gaussian distribution. TCRbeta gene
      repertoire in the 8 patients with SLE were abnormally. Four patients expressed
      TCRbetaV13.1 gene preferentially. Three patients had TCRbetaV8, TCRbetaV9 and
      TCRbetaV18 genes over expressed. These over expressive genes represented the
      oligoclonal expansion of T cell populations. After APBSCT the TCRbeta gene
      repertoires regained CDR3 polymorphism in 5 patients, some of them recovered to
      normal completely. The sequencing analyse show dense and strong band in map of
      TCRbeta gene repertoires were T cell monoclonal or oligoclonal expansion
      frequently. In a case of SLE an amino acid sequence of TCRbetaV8 CDR3 was same to
      a sequence of disease correlative T cell clone with ankylosing spondylitis that
      had been reported in a literature before. CONCLUSION: SLE patients have
      oligoclonal expansion of T cell that related with the pathogenesis of autoimmune
      disease. After APBSCT, T cell clones recover to normal distribution. T cell
      clones that related with disease have been suppressed during immunological
      reconstitution. It may be a main reason the SLE get remission after
      transplantation.

PMID- 14642096
TI  - [Prospective study of pamidronate disodium in treatment of Paget's disease of
      bone].
AB  - OBJECTIVE: To determine the efficacy of pamidronate disodium (pamidronate) in
      treatment of Paget's disease of bone. METHODS: Intravenous drip of pamidronate
      was given at the dose of 30 - 60 mg per day for 2 - 3 weeks with a total dosage
      of 90 - 270 (168 +/- 84) mg to 5 patients with Paget's disease of bone, 2 males
      and 3 females, aged 27 - 74 (61 on average) with the course of disease of 4 - 48
      years (24 years on average), all of them having multiple bone lesions, 2 being in
      grade 4 of pain assessment and bedridden and 3 being in grade 3 with impaired
      mobility. Pain assessment, biochemical markers of bone turnover, including serum
      alkaline phosphatase (ALP), carboxy-terminal propeptide of type I collagen
      (PICP), carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and
      urinary hydroxyproline (HOP), and side effects of pamidronate were observed
      before treatment, by the end of treatment, and 4, 12, 24, and 48 weeks after
      treatment. RESULTS: The Pagetic bone pain was significantly reduced by the end of
      treatment in all patients. The degree of pain assessment declined from grade 4 to
      grade 2 in 2 patients, and from grade 3 to grade 1 in 3 patients. The mobility
      was markedly improved without bone pain 12 weeks after treatment and relief of
      pain lasted for 1 year in all patients. Serum ALP, PICP, ICTP and urinary HOP
      concentrations were significant decrease by the end of treatment. Moreover, the
      mean percentage decreases for above biochemical markers at 12 and 24 weeks after
      treatment were 50% or over. The values of serum ALP, PICP, ICTP and urinary HOP
      decreased from 398 u/L (median), 818 ng/L (median), (29 +/- 14) ng/L and (71 +/-
      16) mg/24 h urine respectively to 159 u/L, 129 ng/L, (12 +/- 4) ng/L and (34 +/-
      7) mg/24 h urine respectively 48 weeks after treatment (all P < 0.05). Side
      effects, including a transient increase in body temperature, skin eruption and
      pruritus, and a transient increase of serum aspartate aminotransferase
      concentration, were negligible. CONCLUSION: Intravenous infusion of pamidronate
      is effective on Paget's disease of bone. Pamidronate of the dose of 90 - 270 mg
      administered within 2 - 3 weeks produces a year-long remission. Side effects of
      pamidronate are slight and transient.

PMID- 14642097
TI  - [Inquire into factors influencing recurrence following resection of carcinoma of
      the head of pancreas].
AB  - OBJECTIVE: Inquire into factors influencing recurrence following resection of
      carcinoma of the head of pancreas to raise survival rate of pancreatic cancer.
      METHODS: We performed a retrospective review of 56 pancreatic resections with
      carcinoma of the head of pancreas operated from January 1995 to December 1998. 35
      patients tolerated the Whipple operadure in comparison with 21 patients received
      the extended radical operation contemporaneously. All patients were followed up
      more than 3 years to find out factors influencing recurrence following resection
      of carcinoma of the head of pancreas. RESULTS: Deaths within 3-years after
      operation were due to recurrence, the cumulative rate of death from recurrence
      51.4% in the Whipple procedure and 42.9% in the Extended radical operative
      procedure, significant difference in two groups. CONCLUSION: Tumour size exceed 4
      cm with severe retropancreatic invasion, lymph node involvement surpass the
      second group are at high risk for recurrence.

PMID- 14642098
TI  - [The clinical significance of expression of cyclooxygenase-2 gene in breast
      cancer].
AB  - OBJECTIVE: To investigate the expressions of Cyclooxygenase-2 (COX-2) gene and
      protein in breast cancer, and understand its clinical significance. METHODS:
      Reverse transcription-PCR, immunohistochemistry were used to assess the
      expression of COX-2 in 30 cancerous tissues, paired tissues adjacent to breast
      cancers and 6 normal tissues far from neoplasm. RESULTS: Strong expression of COX
      2 mRNA was detected in 86% of breast cancers with range of 0 - 1.180 with
      reference to the expression of beta-actin gene, and increased expression in
      paired tissues adjacent to cancers with range of 0 - 0.652, but nearly no
      expression in normal tissues. There were significant difference expression of COX
      2 mRNA between cancers and paired tissues adjacent to cancers or normal tissues.
      Immunohistochemical analysis showed that COX-2 were expressed in 80% malignant
      epithelial cells, and 58% of paired tissues adjacent to cancers, no expression in
      normal tissues. CONCLUSION: Expressions of COX-2 gene and protein elevated not
      only in most human breast cancers, but also in paired tissues adjacent to
      cancers. Up-regulation of COX-2 is relatively early event in mammary
      carcinogenesis, nonsteroidal anti-inflammatory drugs and selective COX-2
      inhibitors may be useful in the chemoprevention and therapy of human breast
      cancer.

PMID- 14642099
TI  - [Age-specific reference ranges for serum prostate-specific antigen in Chinese
      men].
AB  - OBJECTIVE: To evaluate the age-specific reference ranges for serum prostate
      specific antigen in Chinese men. METHODS: Serum tPSA and fPSA were measured by
      enzyme-linked immunosorbent assay (ELISA) and fPSA/tPSA ratio was calculated in
      1,096 health Chinese men of 23 - 85 years old. The relationship between age and
      PSA indexes was analyzed with simple linear regression. RESULTS: The recommended
      age-specific reference range (95th percentile) for serum PSA for Chinese were:
      1.20 microg/L for 20-29 years; 1.21microg/L for 30-39 years; 1.23 microg/L for 40
      49 years; 2.35 microg/L for 50-59 years; 3.20 microg/L for 60-69 years; 3.39
      microg/L for >or= 70 years. The serum PSA concentration correlated directly with
      age. The age-specific reference range was lower for Chinese men than not only for
      white and black men, but also for Japanese and Koreans men. CONCLUSION: The age
      specific reference ranges for serum PSA are lower significantly for Chinese men
      than for black, white men, even for Japanese and Koreans men. Study the normal
      upper limit of PSA and the age-specific reference ranges for serum prostate
      specific antigen in Chinese men is very important.

PMID- 14642100
TI  - [Long-term outcome of bronchoplastic procedures in the treatment of lung cancer].
AB  - OBJECTIVE: To assess the value of bronchoplastic procedures in surgical treatment
      for bronchogenic carcinoma. METHODS: Bronchoplastic procedures were performed in
      78 patients with bronchogenic carcinoma from August 1976 to December 2002. There
      were 67 patients with squamous cell carcinoma (86%). Of the total, 57 patients
      underwent sleeve resection of the right upper lobe (including 2 undergoing
      bronchoplasty and angioplasty; 2 undergoing partial carinal plus lobar
      resection); 1 patient had sleeve bilobectomy of the right upper and middle lobes;
      2 patients had sleeve bilobectomy of the right middle and lower lobes. Sleeve
      resection of the left upper lobe was accomplished in 12 patients (including 3,
      undergoing bronchoplasty and angioplasty), 5 patients had sleeve lobectomy of the
      left lower lobe. Postoperative pathological staging: 47 in stage I (60.2%), 23 in
      stage II (29.5%), 8 in stage III (10.3%). RESULTS: No operative death occurred in
      30 days. Complications were noted in 5 patients (6.6%), including pneumonia (2
      patients) and atelectasis (3 patients). The overall 5-year survival for 78
      patients was 57.8% (26/45), 43% (6/14) respectively. The 5-year survival for
      patients in stage I, II and III was 68.7% (22/32), 36.4% (4/11) and 0 (0/2)
      respectively. CONCLUSION: Bronchoplastic procedures for bronchogenic carcinoma
      extends operative indication to some patients with complication rates comparable
      to pneumonectomy and improve life quality.

PMID- 14642101
TI  - [Reversion of ovarian carcinoma metastasis by adeno-associated virus-mediated
      gene transfer of nm23H1 in orthotopic implantation model].
AB  - OBJECTIVE: To explore the feasibility of reverse effect of recombinant nm23H(1)
      adeno-associated virus (rAAV-nm23H(1)) in ovarian carcinoma metastatic orthotopic
      implantation nude model. METHODS: Using DNA recombination technique to construct
      AAV main plasmid pUF(1)-nm23H(1). rAAV-nm23H(1) and rAAV-Laz were produced by co
      transfection of rAAV system in package cell 293 by phosphate-calcium deposit
      method, and then the transfection efficiency was measured. The titer was measured
      by dot hybridization. Ovarian carcinoma cell line SW626 was used in the
      establishment of the ovarian carcinoma orthotopic implantation nude model. The
      biologic feature of the model was observed and the expression of nm23H(1) in the
      tumor was measured by Western blot. Three groups of ovarian carcinoma orthotopic
      implantation nude model were applied by PBS (as control) (12 mice), rAAV-Laz (13
      mice), rAAV-nm23H(1) (13 mice) intraperitoneally on the day 10 after
      transplantation. Then the effect of rAAV-nm23H(1) on survival and liver
      metastatic incident rates in models were observed. RESULTS: rAAV-nm23H(1) and
      rAAV-Laz were constructed and identified successfully. The titers were both 1 x
      10(10) virus particles/ml. The transfection efficiency was 70%. The observation
      of biological feature showed the orthotopic implantation model was metastatic.
      The expression of nm23H(1) in AAV-nm23H(1) group was higher significantly than
      control and rAAV-Laz group (P < 0.05). Survival time of rAAV-nm23H(1) group was
      136.67 days, compared with blank control group 106.67 days and rAAV-Laz group
      107.06 days. Kaplan-Meier analysis showed rAAV-nm23H(1) group survived longer
      than control and rAAV-Laz group (P = 0.0051, P = 0.018 P < 0.05). The control and
      rAAV-Laz groups showed no statistically difference in survival time (P = 0.059 P
      > 0.05). The metastatic incident rate of control, rAAV-Laz and rAAV-nm23H(1)
      group was 75%, 61.5%, and 30.8% respectively, the rate of rAAV-nm23H(1) group was
      lower significantly than that of control and rAAV-Laz group (P = 0.03, P = 0.01).
      There was no significant difference between control and rAAV-Laz group in liver
      metastatic rate (P > 0.05). CONCLUSION: SW626 line which expressed lower level of
      nm23H(1) showed high-frequency metastasis properties, rAAV-nm23H(1) could reverse
      its metastasis in ovarian carcinoma orthotopic transplantation model.

PMID- 14642102
TI  - [Clinical application of tissue engineered bone repair of human
      craniomaxillofacial bone defects].
AB  - OBJECTIVE: To explore the feasibility of tissue engineered bone formation in
      human being using human bone marrow stromal cells (hBMSCs) and the possibility of
      clinical repair of craniomaxillofacial bone defects with tissue engineered bone.
      METHODS: Total 11 patients of cranial defects and aperture piriformis bone
      depression were included in this study. The hBMSCs were isolated by Percoll
      gradient centrifugation from patient's bone marrow aspirated from iliac crest.
      The hBMSCs were cultured in vitro and induced to become osteogenic cells in the
      DMEM medium containing 10% self-serum, beta-glycerophosphate (10 nmol/L)
      dexamethasone (10(-8) mol/L), L-2-ascorbic acid (50 micro mol/L), and 1, 25
      (OH)(2)VD(3)(10 nmol/L). Induced hBMSCs of passage 3 were harvested and seeded
      onto partly demineralized allogenic bone matrix (pDBM) to form a cell-scaffold
      construct and in vitro co-culture for 1 week. The defects were repaired with the
      cell-scaffold construct. In 3 cases of aperture piriformis bone depression, one
      side was repaired with hBMSC/pDBM, while the other side was repaired by pDBM
      alone. All cases were followed up for 1, 3, 6 months post-operation as short-term
      evaluation and 1 to 2.5 years post-operation as long-term evaluation by three
      dimensional computerized tomography (3D-CT) and clinical examination. In 2 cases
      who received secondary surgery, extra engineered bone tissue and control pDBM
      were harvested at the implantation sites for histological examination and
      immunohistochemistry. RESULTS: 3D-CT demonstrated that engineered bone was formed
      in 3 to 6 months post-operation. Additionally, formed bone maintained stable up
      to 1 - 2 years without absorption. Histologically, engineered bones revealed
      their structures similar to that of normal bone in HE staining. Interestingly,
      endochondral ossification was also observed in engineered bone.
      Immunohistochemistry shows positive staining of osteonectin and osteocalcin in
      engineered and normal bones. In contrast, implanted pDBM was completely degraded
      in 3 - 6 months as revealed by 3D-CT. Histologically, degraded pDBM and fibrous
      tissue were observed in the sites where pDBM alone was implanted. CONCLUSIONS:
      Tissue engineered bone can be formed in human being. Engineered bone can be used
      to repair clinical bone defect with satisfactory result. Furthermore, the result
      of this study proves that tissue engineered bone is possible for clinical
      application.

PMID- 14642103
TI  - [Immunohistochemical localization and expression of fibromodulin in the
      periodontium].
AB  - OBJECTIVE: To study the distribution and expression of fibromodulin in normal
      periodontium, so as to understand its role in periodontal tissue homeostasis.
      METHODS: Five normal male Lewis rats were killed and their bilateral mandibular
      first molars with surrounding alveolar bones and gingival tissues were taken out.
      Human gingival fibroblasts, fibroblasts of periodontal ligament, and osteoblasts
      were cultured. Immunohistochemistry with anti-fibromodulin, anti-decorin, anti
      biglycan, anti-type I collagen, and anti-type III collagen antibodies and RT-PCR
      were used to detect the tissue distribution and cellular localization of
      fibromodulin and related proteoglycans, decorin and biglycan, and type I and type
      III collagens. RESULTS: Fibromodulin was strongly expressed in the suprabasal
      gingival epithelium, periodontal ligament, alveolar bone, gingival and
      periodontal fibroblasts as well as their matrices. Strong expression was noted in
      the area close to oral gingival aspect and the interfaces of periodontal ligament
      alveolar bone and periodontal-ligament-cementum. Decorin was strongly expressed
      in the area close to the gingival sulcus in gingival tissue. Biglycan was stained
      evidently in gingival epithelium. Fibromodulin, decorin and biglycan mRNAs were
      strongly expressed in osteoblasts. mRNAs of type I and type III collagens were
      strongly expressed in gingival fibroblasts. CONCLUSION: Fibromodulin may interact
      with other small proteoglycans to regulate the network formation of periodontal
      collagen fibers, and may be involved in mineralization of the alveolar bone and
      cementum.

PMID- 14642104
TI  - [Transdifferentiation of stem cell antigen-1 positive cells from murine fetal
      liver into renal cells: an experimental study].
AB  - OBJECTIVE: To explore the plasticity and potential of transdifferentiation of
      stem cell antigen-1 positive cells (Scan-1(+) cells) from murine fetal liver into
      renal cells. METHODS: The Scan-1(+) cells from the livers of male murine fetuses
      aged 14.5 days were separated with Magnetic cell sorting (MACS) technology. 2 x
      10(3) Scan-1(+) cells from the male murine fetuses of the same litter were
      transplanted through the caudal vein into 6 female mice of the same line aged 8 -
      12 weeks irradiated with the lethal dosage of gamma ray from (60)Co source (10
      Gy). 6 mice were transplanted with adult wale mariue bone marrow sca-1(+) cells
      and used as experimental controls. Three mice just undergoing irradiation without
      transplantation was used as blank controls. Sixty days after the transplantation
      the mice were killed and their kidneys were taken out. Fluorescence in situ
      hybridization (FISH) test with Y chromosome probe was used to detect cells
      originated from the source of male donors. Histochemistry with biotin-labeled
      ricinus communis agglutinin (RCA) and vimentin and immunohistochemistry with
      antibody of white blood cell common antigen CD45 and antibody of macrophage
      F(4/80) were used. RESULTS: 3 control mice and 2 of the 6 mice transplanted with
      fetal liver cells died 12, 14, and 15 days and 20 and 26 days respectively after
      irradiation. In the mice transplanted with Sca-1(+) cells only one died 14 days
      after irradiation and the remaining mice survived to the date to be sampled. FISH
      technique showed cells with Y chromosome in the epithelium of renal tubules of
      the female mice transplanted with Sca-1(+) cells. RCA(+)/CYP(1A2)(+)/CD(45)(
      )/F(4/80)(-) and vimentin(+)/CD(45)(-)/F(4/80)(-) cells were found in the
      epithelial cells of renal tubules and glomeruli respectively. CONCLUSION: Scan
      1(+) cells most of which are hematopoietic stem cells from murine fetal liver can
      transdifferentiate into renal cells.

PMID- 14642105
TI  - [Expression of midkine and its relationship with HBV infection in hepatocellular
      carcinomas].
AB  - OBJECTIVE: To investigate expression of midkine (MK) in hepatocellular carcinoma
      (HCC) and its relationship with HBV infection. METHODS: Expression of MK mRNA, MK
      protein and HBV DNA were determined in 62 cases of human HCC and 10 cases of
      controls with in situ hybridization and immunohistochemistry. RESULTS: Positive
      rates of MK mRNA and MK protein in carcinoma tissue were 74.2% and 75.8%
      respectively, which were higher than in paratumorous liver tissue and normal
      controls (P < 0.01). Positive rate of HBV DNA in the nuclei of carcinoma tissue
      (62.9%) were higher than in paratumorous liver tissue (6.5%) (P < 0.01). There
      was a significant relationship between expression of MK mRNA and MK protein in
      the carcinoma tissue and HBV DNA in the nuclei of carcinoma tissue. CONCLUSIONS:
      HCC overexpresses MK at the mRNA and protein level. The overexpression of the MK
      protein might be correlated with the existence of HBV DNA in the nuclei of
      carcinoma tissue.

PMID- 14642106
TI  - [Type I hereditary protein C deficiency due to C5498T mutation in protein C
      gene].
AB  - OBJECTIVE: To identify the gene mutation in a Chinese pedigree of type I
      hereditary protein C deficiency. METHODS: The plasma levels of protein C activity
      (PC:A), protein C antigen (PC:Ag), protein S activity, and anti-thrombin activity
      (AT:A) of the propositus, male, aged 7, and 11 members of the pedigree were
      detected using ELISA and chromogenic assay respectively. All of the nine exons
      and intron-exon boundaries of protein C gene of the propositus were analyzed by
      direct sequencing of the corresponding amplified PCR products in DNA from the
      propositus. Restriction enzyme site analysis was used to confirm the mutation.
      RESULTS: The plasma concentrations of protein C activity and antigen of the
      propositus were 26% and 1.43 g/L respectively. The PC:Ag and PC:A of his father
      were normal. Decreased PC:A level was seen in his mother and 4 of his maternal
      pedigree. PS:A and AT:A were all normal in all of the pedigree members. A C5498T
      heterozygous mutation in exon 3, resulting in the substitution of Arg for Trp at
      the 15th amino acid, was identified in the propositus and 8 of his relatives.
      This mutation was confirmed by restriction enzyme site analysis. Mutations C/T at
      position 2405, A/G at position 2418, and A/T at position 2583 in the protein C
      promoter region were confirmed in the propositus and all members of the pedigree.
      CONCLUSION: C5498T heterozygous mutation in exon 3 of protein C gene, first
      reported in China, leads to type I hereditary.

PMID- 14642107
TI  - [Retrospective analysis of 304 cases of malignant lymphomas in pathology: study
      and practice of the WHO classification of lymphoid neoplasms].
AB  - OBJECTIVE: To evaluate the practical application of the WHO classification of
      lymphoid neoplasms, and to investigate the relative frequency and geographic
      distribution of the subtypes of lymphoma. METHODS: The pathological specimens of
      304 cases with lymphoma diagnosed during the period 1994 approximately 2002 in
      the First Hospital of Peking University were retrospectively studied. The
      histopathologic, immunophenotypic and clinical data were reviewed and reappraisal
      was performed according to the WHO classification. RESULTS: There were 20 cases
      (6.6%) of Hodgkin's lymphoma (HL) and 284 cases (93.4%) of non-Hodgkin's lymphoma
      (NHL). In the 284 NHL cases, B-cell neoplasms accounted for 60.2% and T/NK-cell
      neoplasms for 39.1%. On subtyping, diffuse large B-cell lymphoma, extranodal NK/T
      cell lymphoma of nasal type, unspecified peripheral T-cell lymphoma, extranodal
      marginal zone B-cell lymphoma of MALT type, angioimmunoblastic T-cell lymphoma
      and follicular lymphoma were the most common 6 subtypes and amounted to 88.03% of
      NHL. The distribution of NHL subtype in this group showed important difference
      from those in some areas in the world. Extranodal NK/T cell lymphoma of nasal
      type and other peripheral T-cell lymphoma had a higher frequency, but B-small
      lymphocytic lymphoma and follicular lymphoma were less common in this group than
      in Western countries. CONCLUSION: The new WHO classification may be applicable to
      the diagnosis and subtyping of most lymphomas, making the pathological diagnosis
      easier to practise. A correct diagnosis of ML may be reached by combination of
      clinic, histological and immunological features.

PMID- 14642108
TI  - [Autologous transplantation of recombinant interleukine-2 activated bone marrow
      for acute promyelocytic leukemia].
AB  - OBJECTIVE: To explore the benefit of autologous transplantation of interleukine-2
      activated bone marrow (ABM) in acute promyelocytic leukemia (APL) as
      consolidation therapy. METHODS: 31 patients with APL, 27 in first complete
      remission (CR1), 3 in CR2, and 1 in partial remission (PR) after the second
      relapse, were treated with autologous transplantation of ABM. The conditioning
      regimens included MACC protocol (Melphalan, Ara-C, CTX, and CCNU) in 26 patients
      and TBI + CY protocol in 5 patients. The PML/RARa fusion gene was measured by
      fluorescence in situ hybridization. Kaplan-Meier survival analysis model was used
      to estimate the disease-free survival (DFS) rate at 5 years post-transplantation
      and COX regression model was used to analyze the DFS-influencing factors,
      including sex, PML/RARa positive state, pre-transplantation state (CR1, CR2, or
      PR), white blood cell (WBC) count, and platelet (PBC) count. RESULTS: The 27
      patients in CR1 had a DFS time of 3 to 113 months (with a mean DFS time of 46
      months), and a 5-year DFS rate of 100%; none of them suffered a relapse after
      transplantation. One of the 3 patients in CR2 relapsed in 19 months after the
      transplantation and the other two patients had been in DFS state for 7 and 33
      months respectively. The patient in PR obtained CR and relapsed 8 months after
      the transplantation. All the patients showed reconstitution of hematopoiesis.
      None of the patients died of transplantation-related complication. Multivariate
      analysis showed that long-term survival was correlated with the pre
      transplantation statues and not with sex, positivity of PML/RARa, and WBC and PBC
      counts. CONCLUSION: Autologous transplantation of ABM reduces the relapse and
      increases the long-term survival in the patients with APL in CR, especially in
      CR1.

PMID- 14642109
TI  - [Clinical features and misdiagnosis of anti-Jo-1 syndrome: analysis of 33 cases].
AB  - OBJECTIVE: To evaluate the clinical features and causes of misdiagnosis of anti
      Jo-1 syndrome. METHODS: The data of 33 polymyositis (PM)/dermatomyositis (DM)
      patients with anti-Jo-1 antibody hospitalized from January 1997 to June 2002 in
      Peking Union Medical College Hospital were reviewed retrospectively. The initial
      symptom, clinical and laboratory characteristics, diagnosis, efficacy of therapy
      and follow-up were studied. RESULTS: 51.5% of the patients developed lung
      impairment and 24.2% of the patients developed arthritis/arthralgia before the
      onset of PM/DM, only 5 patients had the typical rash, and/or myalgia and muscle
      weakness as the initial symptoms (15.2%). Patients with anti-Jo-1 syndrome were
      usually misdiagnosed as with rheumatoid arthritis (27.3%), idiopathic pulmonary
      fibrosis (12.1%), and pneumonia (15.2%). Anti-Jo-1 syndrome was associated with
      inflammatory myositis (100%), interstitial lung disease (ILD) (93.9%), fever
      (60.6%), polyarthritis/polyarthralgia (54.5%), Raynaud's phenomenon (21.2%), and
      sclerodactyly (21.2%). The muscle symptom was relatively mild and the symptom of
      ILD was relatively severe. Treatment of corticosteroid plus immunosuppressive
      drugs was effective in achieving initial remission, while relapse was frequent.
      CONCLUSION: Few patients with anti-Jo-1 syndrome have the episode of classical
      myositis as initial symptom. Lung impairment, especially ILD, and joint
      involvement are more common in early phase of the disease.

PMID- 14642110
TI  - [Living donor liver transplantation treatment of Wilson's disease complicated
      with neuropathy].
AB  - OBJECTIVE: To investigate living donor liver transplantation for Wilson disease
      with neurologic features. METHODS: From Jan 2001 to Mar 2003, fifteen cases of
      living donor liver transplantation were performed for Wilson Disease (WD), five
      of those were complicated with neurologic features. A retrospective analysis was
      given for cooper metabolism and neurologic features. RESULTS: All operation were
      living related liver transplantation and donors were mothers. Four left lobes
      with hepatic middle vein and one right lobe without hepatic middle vein were
      harvested from donors, and graft volume to recipient body weight ratio was 0.79
      approximately 1.08. One patient occurred hepatic artery thrombosis and performed
      retransplantation later, the other recipients recovered satisfactorily. All
      patients showed Extrapyramidal sign and three patients companying with language
      handicap and dyskinesia alleviated postoperation follow-up between 2 and 16
      months. All recipients are alive and remain well, and none have developed signs
      of recurrent WD. CONCLUSION: Living donor liver transplantation is effective
      treatment for WD complicated with nervous system symptom, ceruloplasmin is normal
      and Kayser-Fleischer ring and nervous system symptom are to various extents.

PMID- 14642111
TI  - [Identification of a novel inheritable CCM1 gene mutation of 671del AT in a
      Chinese family with cerebral cavernous malformation].
AB  - OBJECTIVE: To investigate the hereditary characters of familial cerebral
      cavernous malformation (FCCM) and the novel gene mutation in a Chinese family.
      METHODS: Head MRI examination and clinical neurological check were performed on a
      Chinese family with one proband of FCCM, female, 27 years old, and 16 family
      members, 9 males and 12 females, and 19 controls, including patients with
      sporadic CCM and other diseases and healthy persons. DNA was extracted from the
      white blood cells of the peripheral blood of the subjects. PCR and DNA direct
      sequencing were used to detect the mutation in CCM1 gene. RESULTS: Head MRI found
      11 FCCM patients in the 16 family members of the proband (69%), the youngest one
      being 4 years old, including multiple intracranial lesions in 7 patients and
      single lesion in 4. Relevant clinical manifestations were found in 6 out of the
      11 family members. Nucleotide sequence analysis of the proband and other affected
      family members revealed a deletion frameshift mutation of A and T at nucleotides
      (nt) 671 and 672 in exon 13 of the CCM1 gene, resulting in truncated encoding
      KRIT1 protein. No mutation was detected in the healthy family members and the
      controls. CONCLUSION: A novel inheritable CCM1 gene mutation of 671del AT has
      been found in patients with FCCM.

PMID- 14642112
TI  - [Gamma knife radiosurgery for trigeminal schwannomas].
AB  - OBJECTIVE: To evaluate the role of gamma knife (GK) in the treatment of
      trigeminal schwannomas. METHODS: From June 1994 to June 2000, 38 patients with
      trigeminal schwannoma treated with GK radiosurgery were reviewed. GK was the
      primary treatment modality in 30 cases and followed microsurgery in 8 cases. Of
      the 38 tumors, 12 had small cysts within the tumors, the rest were solid. The
      mean diameter of the 38 tumors was 32 mm (range: 16 approximately 48 mm) and the
      tumors ranged in volume from 2 to 33 cm(3) (with a mean mean volume of 9 cm(3)).
      The maximum dose irradiated to tumor was 20 to 33 Gy (mean: 26 Gy), the tumor
      margin dose ranged from 11 to 15 Gy (mean: 13 Gy). RESULTS: 35 patients had been
      followed for 26 to 98 months (mean: 65 months). 20 had been followed more than 60
      months. Mild numbness or diplopia relieved completely in 12 patients after GK
      treatment. Improvement of neurological deficits was seen in 11, unchanged
      dysfunction or slightly worsening of trigeminal nerve deficits in 9. Three
      patients had mild worsened symptoms at different time because of tumor
      progression. Tumor growth control: tumor disappeared after GK treatment was
      observed in 5 cases from 18 to 36 months after, a marked decrease in volume was
      observed in 24 cases, unchange in 2 cases and increase in 3 cases at 5, 26, and
      60 months after respectively. One patient with resolved symptom refused to have
      MRI examination for more than 6 years. Of the three increased tumors, one
      recurrent malignant schwannoma elapsed 26 months after GK treatment. The second
      was a small tumor and started to progress 5 years after, but after second GK
      treatment, the tumor decreased again. The third was large tumor and was
      subtotally removed through surgery because of tumor swelling 5 months after. At
      last follow-up, the residual tumor remained stable. The control rate of the 35
      tumors was 91% (32/35). CONCLUSION: Small and middle-size trigeminal schwannomas
      are the best candidates for GK radiosurgery. The control dose is 13 to 14 Gy.

PMID- 14642113
TI  - [The application of intravascular ultrasound imaging in identifying the visceral
      artery in aortic dissection].
AB  - OBJECTIVE: To study the role of intravascular ultrasound (IVUS) imaging in
      identifying the visceral artery in aortic dissection. METHODS: Twenty-two
      patients with aortic dissection were studied by IVUS via a femoral approach. The
      relationship between the visceral artery origin and the true and false lumens
      were differentiated by IVUS. The detection rate of visceral artery by IVUS was
      compared with those of CT and digital subtraction angiography (DSA). The cause of
      visceral ischemia was determined by the relationship between the intimal flap and
      the visceral artery origin in IVUS findings, and compared with routine
      examinations. RESULTS: The outer wall of the true lumen had a three layer
      structure while that of the false lumen had only one layer structure in IVUS
      imaging. There was an acute angle between the outer wall of the false lumen and
      the intimal flap at the true and false lumen junction. The thrombosis in the
      false lumen could be detected by IVUS. These features can assist in the
      differentiation of the true and false lumen. The relationship between the
      visceral artery origin and the true and false lumen could be determined in 81 out
      of 84 arteries, among which 54 were originated from the true lumen, and 27 from
      the false lumen. The detecting rate of visceral arteries by IVUS was 96.4%,
      higher than CT (70.2%) and DSA (84.5%), chi(2) = 20.74 and 6.91, P < 0.01. Static
      narrowing in 6 arteries and dynamic narrowing in 1 artery were visualized by
      IVUS, while only 2 static narrowings could be detected by CT. CONCLUSIONS: IVUS
      has an advantage over routine examinations at detecting visceral artery origin
      and clarifying the mechanism of visceral ischemia.

PMID- 14642114
TI  - [Expression of urokinase-type plasminogen activator and its receptor in plasma of
      patients with cerebral infarction].
AB  - OBJECTIVE: To measure the urokinase-type plasminogen activator (UPA) and its
      receptor (UPAR) in the plasma of patients with cerebral infarction and to study
      the effects of UPA and UPAR on cerebral infarction. METHODS: ELISA sandwich
      method was used to measure the plasma levels of UPA and UPAR in 89 patients with
      acute cerebral infarction, subdivided into mild, moderate and severe subgroups
      according to the modified Edinburgh-Scandinavia stroke scale (mESSS), and 30
      patients with other disease and 30 healthy persons as controls. RESULTS: Within 2
      days after the onset of cerebral infarction the UPA and UPAR levels were (1663.7
      +/- 384.2) ng/L and (1 375.3 +/- 303.0) ng/L respectively, both significantly
      higher than those of the patients with other diseases [(1 033.0 +/- 122.7) ng/L
      and (978.3 +/- 120.0) ng/L respectively (P = 0.038 and P = 0.000)] and those of
      the normal control group [(1 005.0 +/- 128.9) ng/L and (904.7 +/- 158.6) ng/L
      respectively, both P = 0.000]. Two weeks after the onset of stroke, the plasma
      UPA level was (1 185.5 +/- 384.6) ng/L, not significantly different from those of
      the 2 control groups (both P > 0.05); while the plasma UPAR level in the cerebral
      infarction was (1 159.3 +/- 261.2) ng/L, significantly higher than those in the 2
      control groups (P < 0.01). Within 2 days after the onset of infarction the plasma
      UPA and UPAR levels of the severe subgroup were (1 938.9 +/- 256.5) ng/L and (1
      510.8 +/- 378.7) ng/L respectively, both significantly higher than those of the
      moderate subgroup [(1 593.7 +/- 204.8) ng/L and (1 296.6 +/- 151.2) ng/L
      respectively, both P < 0.01] and those of the mild subgroup [1 358.5 +/- 175.9]
      ng/L and (1 226.8 +/- 98.3) ng/L respectively, both P < 0.01], Two weeks after
      the onset of stroke,the plasma UPA and uPAR levels of the severe subgroup
      remained significantly higher than those of the mild subgroup [(1 152.6 +/-
      170.3) ng/L vs (1 041.9 +/- 187.0) ng/L, (P < 0.05)] and [(1 186.4 +/- 158.3)
      ng/L vs (1 053.9 +/- 109.4) ng/L, (P < 0.01)]. In addition, the plasma UPA and
      UPAR levels of the patients who died from cerebral infarction at last were the
      highest among all the groups. CONCLUSION: The plasma levels pf UPA and UPAR
      increase in patients with cerebral infarction and may be related with the
      severity of disease. The UPA and UPAR genes may play an important role via
      proteolytic degradation of the extracellular matrix and basement membrane during
      the development of cerebral infarction.

PMID- 14642115
TI  - [Prognostic value of MRI and 1H MRS in patients with temporal lobe epilepsy].
AB  - OBJECTIVE: To evaluate the prognostic value of hippocampal MRI scan, MRI
      volumetry and 1H MRS in patients with temporal lobe epilepsy (TLE). METHODS: 50
      intractable TLE patients operated in Huashan hospital were studied. Before
      surgery, traditional MRI scans were used to exclude tumor and vascular
      malformation of the brain. All patients were examined by tilted coronal images
      which were perpendicular to the long axis of the hippocampus, using T1-weighted,
      T2-weighted and FLAIR sequence. MRI volumetric measurement of both hippocampal
      formation were performed. 38 patients also took 1H MRS scan. Unilateral anterior
      temporal lobectomy was performed in all patients and pathology showed different
      degrees of hippocampal sclerosis. The prognosis was categorized into three grades
      with grade I being assigned to the group of good outcome, and grade II and III
      being assigned to the bad outcome group. Correlative analysis between the results
      of several examinations and the prognosis were performed respectively. RESULTS:
      MRI-positive cases with hippocampal scans were about 84% of the 50 cases.
      Hippocampal atrophy, increase of signal intensity or the loss of internal
      morphological structure were detected. 98% of the MRI-positive patients had good
      outcome, and 38% of the MRI-negative patients had good outcome. The prognosis
      between MRI-positive group and MRI-negative group had significant difference
      (chi(2) = 23.00, P = 0.000). Among the right-side operated cases, the average
      hippocampal volume on the operated side of the bad outcome group was larger than
      that of the good outcome group. While among the left-side operated cases, the
      hippocampal volume on the non-operated side of the bad outcome group was smaller
      than that of the good outcome group. Significant differences were found in
      statistics respectively. In both groups, prognosis was found to be statistically
      related to the DHF value (difference of bilateral hippocampal volume). The DHF
      value of the good outcome group was larger than that of the bad outcome group. 38
      patients took 1H MRS examination. The average NAA/(Cr + Cho) ratio on the
      operated side of the patients in the bad outcome group was greater than that of
      the good outcome group. The average NAA/(Cr + Cho) ratio on the contralateral
      side of the patients in the bad outcome group was lower than that of the good
      outcome group. But no significant differences were found in statistics
      respectively. 90% cases of MRS unilateral abnormalities had good outcome, while
      77% cases of MRS bilateral abnormalities had good outcome. But no statistically
      significant difference was found among different groups (chi(2) = 0.493, P =
      0.781). CONCLUSION: Hippocampal MRI scan, MRI volumetry and 1H MRS may be used as
      prognostic tools in TLE patients before surgery. The combination of several
      noninvasive methods before surgery can help choose suitable patients for surgery,
      and, as a result, improve surgical outcome.

PMID- 14642116
TI  - [Directional development and differentiation of mouse embryonic stem cells into
      hepatocytes in vitro].
AB  - OBJECTIVE: To investigate the mechanism and regulation of differentiation from
      embryonic stem (ES) cells to hepatocytes in vitro and to find a new source of
      cell types for hepatocytes replacement therapies in the treatment of hepatic
      failure. METHODS: ES cells of BALB/c mice were cultured and maintained
      undifferentiated in gelatin-coated dishes in Dubecco's modified Eagle's medium
      (DMEM) containing 1 000 U/L leukaemia inhibitory factor (LIF). Then, the ES cells
      were cultured in DMEM without LIF so as to develop into embryonic bodies (EBs).
      For directional differentiating, EBs were put into 24-well tissue culture dish
      and differentiate into cells with different forms. On day 7 to day 11 acid
      fibroblast growth factor (aFGF) with terminal concentration of 100 ng/ml was
      added, and on day 11 to day 15 hepatocyte growth factor (HGF) terminal
      concentration of 20 ng/ml was added. EBs in culture without growth factor was
      used as controls. The development and differentiation status was observed by
      inversion microscope dynamically. The concentrations of alpha-fetoprotein (AFP)
      and albumin (ALB) in the supernatants were determined by radioimmunoassay on the
      1st to 15th day since the ES cells were inoculated. Immunocytochemistry (ICC) was
      used to detect the expression of hepatic proteins such as AFP, ALB, cytokeratin 8
      (CK8) and cytokeratin 18 (CK18) in the cells on the days 7, 8, 9, 10, 11, 12, 13,
      14, and 15. The number of ALB positive cells was counted. The ALB positive rate
      was calculated as the differentiation ratio of hepatic cells. RESULTS: ES cells
      remained undifferentiated and grew to ES clones in the DMEM containing LIF and
      developed to EBs in the medium without LIF. AFP was detected firstly in the
      medium on day 8 with a concentration of 3.4 ng/ml and the concentration increased
      to be 22.8 ng/ml at day 15; ALB was detected firstly in the medium on day 11 with
      a concentration of 0.2 microg/ml and the concentration increased to be 2.2
      microg/ml on day15. ICC showed that AFP, ALB, CK8, and CK18 began to be expressed
      on day 8, day 10, day 10, and day 11 respectively. The ICC-positive cells have
      the ultrastructures consistent with those of the normal mouse hepatocytes. The
      ratio of hepatic differentiation was 30%. CONCLUSION: ES cells can differentiate
      directionally into hepatocytes when cultured in gelatin-coated dish and medium
      with aFGF and HGF. This ES cell differentiating system provides enough functional
      hepatocytes and may be a good new source of differentiated cell types for
      hepatocytes replacement therapies in treatment of hepatic failure.

PMID- 14642117
TI  - [Transfection of nuclear factor-kappaB decoy oligodeoxynucleotides prevents
      ischemic acute renal failure in rats].
AB  - OBJECTIVE: To investigate the effect of nuclear factor kappaB (NF-kappaB) decoy
      oligodeoxynucletides (ODN) on acute ischemic renal failure (iARF). METHODS: The
      right kidney was resected and the left renal artery was isolated so as to
      establish the animal model of iARF in 18 SD rats. Then the 18 rats were divided
      into 3 groups of 6 rats to be infused into the left renal artery with protamine
      liposome (PL)-wrapped NF-kappaB decoy ODN (NF-kappaB group), scrambled ODN
      (scrambled group), or nothing (iARF group) and then underwent clamping of the
      left renal artery for 60 minutes. Another six rats underwent sham operation with
      infusion of normal saline and without clamping of the renal artery (sham group).
      Twenty-four hours later, blood was extracted from the inferior vena cava to
      detect the serum creatinine (Cr) and blood urine nitrogen (BUN). Normal saline
      was infused into the aorta to lavage the kidney. Then the kidney was taken to
      undergo histologic examination and examination of NF-kappaB/DNA binding activity,
      monocyte/macrophage (M/MPhi) infiltration and MCP-1 gene and protein expression.
      RESULTS: In the rats injected with PL-wrapped NF-kappaB decoy ODN fluorescence
      was mainly distributed in the glomeruli 2 hours after injection of NF-kappaB
      decoy ODN, mainly in the renal tubules 12 hours later, and remarkably subsided
      after 24 hours. In the rats injected with un-wrapped NF-kappaB decoy ODN, no
      fluorescence was seen at any time point. After 24 h of reperfusion, compared with
      sham-operated animals, the serum Scr and BUN levels of the iARF group were about
      10-times and 5 times those of the sham operation group (256 micromol/L +/- 84
      micromol/L vs. 25 micromol/L +/- 5 micromol/L and 43 mmol/L +/- 13 mmol/L vs.
      8.45 mmol/L +/- 1.07 mmol/L respectively. both P < 0.001), the NF-kappaB/DNA
      binding activity was markedly elevated [with the median values 1.75 vs. 0.15
      relative density unit (RDU), P < 0.005], the renal tubular damage score was
      significantly higher (3.63 +/- 0.15 vs. 0.00 +/- 0.00 scores, P < 0.01), M/MPhi
      infiltration and the expression of MCP-1 gene were also increased. In comparison
      with the iARF group, the serum Cr level of the NF-kappaB decoy ODN treatment
      group was significantly lowered by 70% (79 micromol/L +/- 21 micromol/L vs. 256
      micromol/L +/- 84 micromol/L, P < 0.01), the renal tubular damage score was
      markedly lower (1.85 +/- 0.15 vs. 3.63 +/- 0.15 scores, P < 0.01), and the M/MPhi
      infiltration and MCP-1 gene expression were inhibited. CONCLUSION: NF-kappaB
      plays a critical role in renal ischemia/reperfusion injury and NF-kappaB decoy
      ODN reduces the renal dysfunction and injury associated with I/R of the kidney.
      In vivo transfection of NF-kappaB decoy ODN provides a novel therapeutic strategy
      for iARF.

PMID- 14642118
TI  - [Glutamate-neuroexcitotoxicity protective study of monoclonal antibody against
      human NMDA receptor key subunit].
AB  - OBJECTIVE: To study if monoclonal antibody against human NMDA receptor key
      subunit (NR1) may protect neurons from excitotoxicity. METHODS: We cultured
      primary hippocampal neurons from 10 newborn rats and made the glutamate
      excitotoxicity model, examined the ratio of surviving neuron (Trypan blue dye
      staining) and LDH assay to study the protective effects of mAbN1, There were 2
      plates in parallel per group, the experiments were repeated 4 times. RESULTS: 0.3
      micro mol/L mAbN1 could protect cultured hippocampal neurons from
      neuroexcitotoxicity induced by 500 micro mol/L glutamate with increased survival
      rate 35%. Epitope peptide could block the protection of mAbN1, which suggests
      that the protection of mAbN1 is specific. CONCLUSION: mAbN1 is a novel NMDAR
      blocker with in vitro neuroprotective activity which may provide a basis for
      antibody therapy of neuroexcitotoxicity.

PMID- 14642119
TI  - [Adenovirus mediate FGF receptor gene transfer inhibits accelerated graft
      arteriosclerosis in rat aortic transplants].
AB  - OBJECTIVE: To evaluate the efficacy of adenovirus mediated fibroblast growth
      factor (FGF) receptor gene transfer in inhibition of accelerated graft
      arteriosclerosis (AGA) in rat aorta transplantation model. METHODS: The PCR
      product of rat sFGFR-1 cDNA was cloned into pCMV1-flag vector, then flag-sFGFR
      was cloned into pAdvs6a to construct recombinant vector pAv3flag-sFGFR1. The
      abdominal aorta was injected with buffer containing 5 x 10(9) pfu Adv3-sFGFR-1
      and then resected in 30 DA rats. A section of abdominal aorta was resected in 30
      PVG rats and the abdominal aorta of DA rats was transplanted. Av3-Nall and normal
      saline of the same volume were injected into the abdominal aortae of and rats as
      experimental controls and blank controls. Six rats were killed 5, 30, 60, and 90
      days after the operation respectively. The transplanted aorta was harvested. RT
      PCR was performed to detect the expression of sFGFR-1 gene with pCMV-Flag-sFGFR1
      cDNA as positive control and the abdominal aorta RNA of non-transfected rats as
      negative control. Immunohistochemistry and HE staning were used to detect the
      localization and expression of sFGFR-1, and the morphology and cytology of the
      transplanted vessels. RESULTS: A construct encoding the FGFR1 ectodomain produced
      secreted sFGFR1 protein, which bound [(125)I]FGF-2 with high affinity and
      specificity, and inhibited FGF-2 stimulated 3T3 fibroblast proliferation in
      vitro. Gene transfer of sFGFR1 into rat aortic grafts, using an adenoviral
      vector, resulted in expression of sFGFR1 protein in endothelium and adventitia.
      Neointimal formation 60 and 90 days after transplantation was inhibited (P =
      0.013) in aortic allograft transduced with sFGFR1, compared to allograft
      transduced with Null virus and saline. CONCLUSION: FGFs play a causal role in the
      development of AGA in the rat aortic transplant model and postulate that targeted
      interruption of FGF function could similarly reduce neointimal formation in
      transplant setting.

PMID- 14642120
TI  - [The roles of dopamine 4 receptor in MPTP-induced gastrointestinal mucosal injury
      in rats].
AB  - OBJECTIVE: Using the dopamine 4 receptor (D(4)) agonist quinpirole (Q.) and
      antagonist clozapine (C.) to investigate the role of D(4) in MPTP induced
      gastrointestinal injury in rat. METHODS: SD rats were randomly divided into 8
      groups (n = 5 approximately 9 each group): NS as control; Q. 0.5 mg/kg; Q. 1
      mg/kg; C. 10 mg/kg; Q. 0.5 mg/kg + MPTP; Q. 1 mg/kg + MPTP; and MPTP l mg/100 g.
      After treated with the different chemicals, the gastric and duodenal mucosa
      lesion index (LI) was recorded. Gastric and duodenal mucosa was collected to
      assay NO and iNOS by spectrophotometer. RESULTS: (1) MPTP peritoneal injection
      induced significant gastro-duodenal mucosa injury; both gastric and duodenal LI
      were 5 approximately 6-fold higher than control group (P < 0.01). (2) Q. or C.
      used alone showed no effect on gastro-duodenal mucosa, Q. used before MPTP could
      resist the MPTP-induced mucosa injury, especially in duodenum (P < 0.01). This
      effectiveness is dose dependent. C. had no effect on gastro-duodenal mucosa
      protection. (3) The mucosal NO concentration and iNOS activity in MPTP group were
      lower than that in control, especially in duodenum (P < 0.05). They were negative
      correlated with LI. CONCLUSION: MPTP peritoneal injection induced significant
      gastro-duodenal mucosa injury in rat, mediated partially by decreasing the
      activity of mucosa iNOS and NO concentration. D(4) agonist Q. could resist the
      effectiveness of MPTP-induced mucosa injury, while the antagonist C. had no
      effect.

PMID- 14642121
TI  - [Effect of endotoxin-induced uveitis on GATA-3 expression and ACAID development].
AB  - OBJECTIVE: To investigate the changes of the GATA-3 expression and development of
      anterior chamber associated immune deviation (ACAID) after anterior chamber (AC)
      injection of interphotoreceptor retinoid binding protein (IRBP) under ocular
      inflammation. METHODS: ACAID was induced by injection of IRBP into the AC of 30
      Spar-Dawley (SD) rats. Then the animals were divided into -4 days group, -24
      hours group, 0 hour group, 3 days group, and 7 days group according to the
      lipopolysaccharide (LPS) injection 4 days and 24 hours before, or 0 hour, 3 days
      and 7 days after IRBP inoculation respectively. 6 rats were used as controls 8
      days after IRBP injection, Serum interleukin-4 (IL-4) was evaluated to count the
      development of ACAID; Western blot and RT-PCR were used to determine the protein
      and mRNA levels of GATA-3 expression. RESULTS: In -24 hours group and 0 hour
      group, the ocular inflammation reached a maximum 24 hours after LPS injection; on
      8 days after IRBP inoculation, serum IL-4 couldn't be detected and GATA-3
      expression were not changed both on mRNA and protein levels compared with control
      group. In -4 days group, the ocular inflammation was subsided gradually 24 hours
      and disappeared 96 hours after LPS injection; serum IL-4 and GATA-3 expression
      were significantly elevated 8 days after IRBP injection. In 7 days group, the
      serum IL-4 and GATA-3 expression in spleen increased 8 days after IRBP
      inoculation. CONCLUSION: In ocular inflammation, the up-regulation of GATA-3
      expression is inhibited and ACAID development is blocked after antigen was
      injected into anterior chamber. Once GATA-3 is up-regulated, LPS injection cannot
      affect ACAID development.

PMID- 14642122
TI  - [The role of lipopolysacchride-binding protein in the pathogenesis of animal
      model of acute necrotizing pancreatitis].
AB  - OBJECTIVE: To explore the pathogenic role of lipopolysacchride-binding protein
      (LBP) in the pathogenesis of acute necrotizing pancreatitis (ANP) by applying
      anti-LBP antibody to the animal model of ANP in mice. METHODS: Sixty BALB/c mice
      were randomly divided into four groups, including ANP group (n = 18), ANP treated
      with anti-LBP antibody group (n = 18), anti-LBP antibody group (n = 18) and
      normal control (n = 6). ANP model was induced by seven times administration of
      cerulein (50 micro g/kg.body weight), challenged by lipopolysaccharide (LPS) (5
      mg/kg) intravenous injection. Treatment with anti-LBP antibody was started 15
      minutes before LPS injection in ANP treated with anti-LBP antibody group. Anti
      LBP antibody group only received intravenous injection of anti-LBP antibody,
      normal saline was administrated intraperitoneally instead of cerulein and LPS. At
      9 h, 12 h and 24 h after the first injection of cerulein (or saline), the serum
      levels of amylase and lactate dehydrogenase (LDH) were measured. The severity of
      pancreatitis was evaluated by histological scoring system. Intrapancreatic TNF
      alpha, IL-1beta, ICAM-1 and E-selectin mRNA expressions were studied by semi
      quantitative RT-PCR. The activation of nuclear factor-kappaB (NF-kappaB) in the
      pancreas was investigated by the methods of immunohistochemistry and Western
      blot. The activity of PMN myeloperoxidase (MPO) was determined by
      zymohistochemistry. RESULTS: Compared with the ANP group, a marked elevation of
      serum amylase was observed 9 h and 12 h after cerulein administration and a
      marked elevation of serum LDH was observed 24 h after cerulein administration in
      the ANP treated with anti-LBP antibody group. Histologically, treatment with anti
      LBP group increased the severity of pancreatic injury including edema at 9 h and
      12 h after, and inflammatory cell infiltration and necrosis 24 h after.
      Intrapancreatic TNF-alpha, IL-1beta, ICAM-1 and E-selectin mRNA levels were
      increased. The activity of MPO was increased significantly 12 h and 24 h after in
      the anti-LBP antibody group. Immunohistochemistry and Western blotting showed up
      regulation of NF-kappaB. However, there was no significant difference in serum
      parameters and pathologic scoring results between LBP antibody group and normal
      control. CONCLUSION: LBP plays a protective role in the pathogenesis of ANP, and
      this action may be mediated by inhibiting of NF-kappaB activation and down
      regulation of proinflammatory mediators.

PMID- 14642123
TI  - [Effects of macrophage infiltration and related gene expression on the
      pathogenesis of early abdominal aortic aneurysm].
AB  - OBJECTIVE: To detect the pathogenic mechanism of early abdominal aortic aneurysm
      (AAA). METHODS: Pig elastinase was perfused into the abdominal aortae of 40
      Wistar rats to construct AAA animal models. The diameter of abdominal aorta was
      measured and then the abdominal aorta was harvested from 10 rats on the
      postoperative days 3, 7, 14, and 28 respectively. The thoracic aorta was used as
      control. HE staining, elastic staining, and CD68 (macrophage specific antigen)
      immunohistochemical staining were used to detect the distribution of elastic
      fiber and macrophage infiltration in aortic tissue. In situ hybridization was
      applied to investigate the mRNA expression of monocyte chemotactic protein-1 (MCP
      1) and matrix metalloproteinase-2 (MMP-2). RESULTS: Three days after the
      operation, the expansion of abdominal aorta began to be seen and peaked 2 weeks
      after operation. Disruption of elastic fiber began to be found in the wall of
      abdominal aorta since 3 approximately 7 days after operation, and reached the
      maximum 2 weeks postoperatively. CD68 positive cell was not found in the wall of
      normal thoracic aorta and began to be found in the wall of abdominal aorta 3
      approximately 7 days after operation. The expression of CD68 protein peaked on
      the day 14 with a significant difference from that on day 3 (t = 5.13, P < 0.01).
      The number of CD58 positive cells was remarkably decreased 4 weeks after
      operation in comparison with that 2 weeks after operation (t = 4.27, P < 0.01).
      The mRNA expression rates of MCP-1 and MMP-2 in the wall of abdominal aorta were
      at their maximal values, (31.5 +/- 5.7)% and (35.2 +/- 7.8)%, on the
      postoperative days 7 and 14 respectively, significantly higher than those at
      other time points (all P < 0.01). The MCP-1 and MMP-2 positive cells began to
      decrease since the 4th postoperative week. CONCLUSION: Macrophage infiltration is
      parallel to MMP-2 mRNA expression and elastic fiber disruption in aortic tissue.
      MCP-1 mRNA expression, as a promoting factor, induces the macrophage
      infiltration, thus contributing to the development and progression of AAA.

PMID- 14642126
TI  - The revival of the ancient drug--arsenic.

PMID- 14642124
TI  - Consensus for the management of severe acute respiratory syndrome.

PMID- 14642127
TI  - Effect of arsenic trioxide on cytokine expression by acute promyelocytic leukemia
      cells.
AB  - OBJECTIVE: To detect the expression of cytokines by acute promyelocytic leukemia
      (APL) cells before and after exposure to arsenic trioxide. METHODS: Diagnoses
      were performed according to the FAB cytological classification criteria and
      cytogenetic criteria. Bone marrow or blood samples from APL patients were
      collected in heparinized tubes, then primary APL cells were separated by
      traditional Ficoll-Hypaque density centrifugation and purified after adherence to
      plastic surfaces. IL-1(beta), IL-6, IL-8, TNF alpha and G-CSF levels in the
      leukemia cell culture supernatants were detected by ELISA. At the same time,
      nitro blue tetrazolium (NBT) reduction test was used to detect the
      differentiation of APL cells. RESULTS: After 96 hours exposure to arsenic
      trioxide, 10 - 6 mol/L in vitro or 10 mg/d in vivo, APL cells showed a
      significant increase of IL-1(beta) (P < 0.05) and G-CSF (P < 0.05) production,
      and a significant decrease of IL-6 (P < 0.05) and IL-8 (P < 0.05). However, there
      was no obvious variation of TNF alpha when compared with APL cells without
      exposure to arsenic trioxide. On the other hand, the proliferation ratio of APL
      cells in vitro was statistically correlated to the IL-1(beta) secretion ratio or
      G-CSF secretion ratio. The cell number ratio in patients with detectable IL
      1(beta) or G-CSF was higher than that without detectable IL-1(beta) or G-CSF.
      CONCLUSION: IL-1(beta) and G-CSF secretion may play an important role in the
      proliferation of APL cells after exposure to arsenic trioxide.

PMID- 14642128
TI  - Arsenic trioxide inhibits p-glycoprotein expression in multidrug-resistant human
      leukemia cells that overexpress the MDR1 gene.
AB  - OBJECTIVE: To investigate the effects of arsenic trioxide (As(2)O(3)) on the
      apoptosis and p-glycoprotein (P-gp) expression of multidrug-resistant human
      leukemia cells. METHODS: Human multidrug-resistant leukemia cell line K562/ADM
      overexpressing the MDR1 gene, was used as the target cells. The cell
      proliferating activity was assessed using the MTT colorimetric assay.
      Cytomorphology was investigated under light, confocal and electron microscopes.
      DNA fragmentation was examined using agarose gel electrophoresis, while p-gp
      expression, cell cycle status and sub-G1 cells were determined using flow
      cytometry. RESULTS: Zero point five to 20 micromol/L As(2)O(3) inhibited the
      proliferation of K562/ADM cells, and K562/ADM cells were more sensitive to
      As(2)O(3) than the parental K562 cells. As(2)O(3)-induced apoptosis of K562/ADM
      cells was determined by the observance of typical morphological changes and the
      appearance of DNA ladder and sub-G1 cell populations. As(2)O(3) significantly
      inhibited the P-gp expression of K562/ADM cells, and synergistically enhanced the
      sensitivity of the drug-resistant cells to adriamycin. CONCLUSIONS: As(2)O(3)
      induces growth-inhibition and apoptosis, down-regulates P-gp expression and
      exerts a synergistic effect in combination with adriamycin in multidrug-resistant
      leukemia cells.

PMID- 14642129
TI  - Efficiency of adenoviral vector mediated CTLA4Ig gene delivery into mesenchymal
      stem cells.
AB  - OBJECTIVE: To prevent Graft-versus-host disease (GVHD) in rat model, we evaluated
      the feasibility of mesenchymal stem cells (MSCs) as a gene transfer target and
      studied the efficiency of recombinant adenovirus mediated gene therapy. METHODS:
      We constructed the recombinant adenovirus containing CTLA4Ig gene. Rat MSCs of
      passages 3-5 were infected by the adenovirus, and the transfection efficiency was
      monitored by GFP markers. We performed flow cytometric analysis,
      immunohistochemical and Western blotting analysis to identify the CTLA4Ig
      expression. The gene transferred MSCs were tested for their ability to inhibit
      the allogeneic lymphocyte response in vitro and to prevent GVHD in a rat model.
      RESULTS: Recombinant adenovirus pAd-CTLA4Ig was correctly constructed and
      confirmed. After MSCs were infected by the adenovirus, the CTLA4Ig protein was
      detected not only in transgenic MSCs, but also in the culture medium. In a mixed
      lymphocytes response (MLR) test, the transgenic MSCs could significantly inhibit
      the allogeneic lymphocyte response compared with the control groups (P < 0.05). A
      model of GVHD was developed by transplanting bone marrow cells and spleen
      lymphocytes of F344 rats to lethally irradiated SD rats. The onset of GVHD could
      be ameliorated or prevented by co-administration of transgenic MSCs. All the rats
      in the control groups suffered severe acute GVHD. CTLA4Ig expression was observed
      in the liver, intestine, kidney and spleen 30 days post-transplantation.
      CONCLUSIONS: Our results indicate that adenoviral vectors could efficiently
      transfer CTLA4Ig gene into MSCs and sustain long-term stable expression in vitro
      and in vivo.

PMID- 14642130
TI  - Induction of T-cell immunity against leukemia by dendritic cells pulsed with
      total RNA isolated from leukemia cells.
AB  - OBJECTIVES: To assess the feasibility and efficacy of eliciting leukemia-specific
      T-cell responses in syngeneic mice in vitro and in vivo using dendritic cells
      (DCs) pulsed with total RNA from leukemia cells. METHODS: DCs generated from bone
      marrow culture in vitro in the presence of combined cytokines were pulsed with
      cellular total RNA isolated from cultured L615 cells by cationic lipid 1,2
      dioleoyloxy-3-(trimethylammonium) propane (DOTAP). T-cell responses were
      evaluated by in vitro proliferation, and cytotoxicity assay. And in vivo immune
      protection and prognosis of mice with leukemia were studied. RESULTS: DCs pulsed
      with total RNA isolated from cultured L615 cells (DCs/RNA) were remarkably
      effective in stimulating L615-specific T-cell response in vitro, but did not
      cross-react with other leukemia cells from syngeneic mice. Vaccination of naive
      mice with viable DCs/RNA vaccine was able to partly protect from challenge with a
      lethal dose of live L615 cells, leading to low leukemia incidence and overall
      survival prolongation. Statistically significant survival was also observed in a
      low lethal dose of L615-bearing mice that received treatment using viable DCs/RNA
      vaccine alone, suggesting that systemic administration of IL-2 could enhance the
      anti-tumor efficacy of leukemia RNA/DCs vaccine. CONCLUSIONS: These data support
      the use of DCs/RNA vaccine as a feasible and effective route to elicit leukemia
      immunity against unidentified leukemia-associated antigens for treatment of
      leukemia-bearing animals.

PMID- 14642131
TI  - LPS-induced NF-kappa B activation requires Ca2+ as a mediator in isolated
      pancreatic acinar cells of rat.
AB  - OBJECTIVE: To investigate the effect of Ca(2+) on lipopolysaccharide (LPS)
      induced NF-kappa B activation in pancreatic acinar cells and the role of NF-kappa
      B in LPS-induced acinar cell injury. METHODS: Male rat pancreatic acinar cells
      were isolated by collagenase digestion, then exposed to varying concentrations of
      LPS (from 1 to 20 mg/L) in the presence or absence of EGTA. At various time
      points (30 minutes, 1 hour, 2 hours, 4 hours and 10 hours) after treatment with
      the agents, cell viability was determined by MTT. Nuclear translocation of NF
      kappa B's subunit p65 was visualized by immunofluorescence staining and nuclei
      protein was extracted to perform EMSA which was used to assay the activity of NF
      kappa B binding to the DNA sequence containing the recognition site of NF-kappa
      B. RESULTS: LPS induced cell damage in a time- and concentration-dependent manner
      while EGTA attenuated LPS-induced cell damage (P < 0.05). NF-kappa B p65
      immunofluorescence staining had increased intensity in the cytoplasm and
      indicated that nuclear translocation occurred within 30 minutes and its zenith
      was reached at 1 hour after LPS (10 mg/L) treatment. Testing of NF-kappa B DNA
      binding activity showed the same alteration phase as p65 immunofluorescence
      staining. NF-kappa B activation preceded the pathological alteration of
      pancreatic acinar cells. The Ca(2+) chelator EGTA inhibited LPS-induced NF-kappa
      B activation. CONCLUSIONS: NF-kappa B activation is an important early event in
      LPS-induced injury to pancreatic acinar cells. Ca(2+) is an important mediator in
      the process of LPS-induced NF-kappa B activation.

PMID- 14642132
TI  - CsA downregulates IFN-gamma gene transcription after liver transplantation by
      inhibiting NF-kappa B activity.
AB  - OBJECTIVE: To investigate the relationship between NF-kappa B activity and IFN
      gamma gene expression, as well as the histopathological changes following liver
      transplants, both with and without cyclosporin A (CsA) treatment. METHODS: Sixty
      male Wistar and Thirty male SD rats were subjected to orthotopic liver
      transplants. Fourty-five of the Wistar rats were used as recipients, and were
      divided into 3 groups: group I, syngeneic control (Wistar-to-Wistar); group II,
      acute rejection (SD-to-Wistar); and group III: acute rejection treated with
      cyclosporin A by intramuscular injection (SD-to-Wistar + CSA). After the liver
      transplants, electrophoretic gel mobility shift assay was used to analyze NF
      kappa B activity in the splenocytes of recipient rats, and RT-PCR was used to
      measure IFN-gamma gene expression in grafted liver specimens. In addition,
      histopathological examinations were performed to assess the severity of acute
      liver rejection. RESULTS: In group I, low levels of NF-kappa B activity were only
      detectable on day 5 and 7 post-transplant, and only weak IFN-gamma mRNA
      expression was observed at all time points. By contrast, both high NF-kappa B
      activity and high expression levels of IFN-gamma mRNA were detected at all time
      points in group II. In group III, NF-kappa B activity and IFN-gamma mRNA
      expression were significantly inhibited, as compared to group II (P < 0.05). A
      good correlation was found between NF-kappa B activity and IFN-gamma mRNA
      expression (r = 0.815). In addition, NF-kappa B activity and IFN-gamma mRNA
      expression mirrored histopathological changes in all three experimental groups.
      CONCLUSIONS: Changes in IFN-gamma mRNA expression levels after liver
      transplantation are at least partially due to changes in levels of NF-kappa B
      activity. CsA appears to downregulate NF-kappa B activity, thus inhibiting IFN
      gamma gene transcription. Blocking the NF-kappa B mediated transcription pathway
      may be of benefit in preventing liver transplant rejection.

PMID- 14642133
TI  - Growth inhibiting effects of terazosin on androgen-independent prostate cancer
      cell lines.
AB  - OBJECTIVE: To study the effects of an alpha(1)-adrenoceptor antagonist, terazosin
      on the androgen-independent prostate cancer cell lines PC-3 and DU145. METHODS:
      Two androgen independent cell lines, PC-3 and DU145, were used to determine cell
      viability, colony-forming ability, as well as cell cycle distribution, after
      exposure to terazosin. Western blot analysis was used to determine the expression
      of p21WAF1 and p27KIP1. RESULTS: This study shows that terazosin inhibits not
      only prostate cancer cell growth but also its colony forming ability, both of
      which are main targets of clinical treatment. In addition, terazosin is shown to
      inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of
      p27(KIP1). CONCLUSION: This study provides evidence that the alpha(1)
      adrenoceptor antagonist terazosin may have therapeutic potential in the treatment
      of advanced hormone refractory prostate cancer.

PMID- 14642134
TI  - Protective effects of alpha 1-antitrypsin on acute lung injury in rabbits induced
      by endotoxin.
AB  - OBJECTIVE: To investigate whether pretreatment with alpha(1)-antitrypsin (AAT)
      can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. METHODS:
      Thirty-two healthy adult New Zealand rabbits were anaesthetized, tracheotomized
      and mechanically ventilated. They were then randomly divided into four groups (n
      = 8): (1) Infusion of Escherichia coli endotoxin [Lipopolysaccharide (LPS) 500
      microg/kg] without AAT (Group LPS). (2) Infusion of AAT 120 mg/kg at 15 minutes
      after LPS (Group LAV). (3) Infusion of AAT 120 mg/kg without endotoxin (Group
      AAT). (4) Infusion of saline 4 ml/kg as control (Group NS). Arterial blood gases,
      peripheral leukocyte counts and airway pressure were recorded every hour for
      eight hours. Physiologic intrapulmonary shunting (Qs/Qt) was measured every four
      hours. After eight hours, blood samples were collected for measurement of plasma
      concentration and activity of AAT. Then, the animals were sacrificed, and
      bronchoalveolar lavage fluid (BALF) was collected for measurement of
      concentrations of total protein (TP), interleukin-8 (IL-8), tumor necrosis factor
      (TNF alpha, the activities of NE and AAT, total phospholipids (TPL) and
      disaturated phosphatidylcholine (DSPC). In addition, the wet-to-dry lung weight
      ratio (W/D) was measured. RESULTS: The infusion of endotoxin induced decreases in
      arterial oxygen pressure (PaO(2)), peripheral leukocyte counts, total respiratory
      compliance (TLC) and the increases in peak pressure (P(peak)), Qs/Qt compared
      with the baseline values (P < 0.05). The increased plasma concentration but
      reduced activity of AAT was also found in contrast to that in Group NS (P <
      0.05). In the BALF, the activity of AAT, TPL, DSPC/TPL were lower than those in
      Group NS (P < 0.05), but the concentrations of albumin, IL-8, TNF alpha, the
      activity of NE and the ratio of W/D were higher than those in Group NS (P <
      0.05). The pretreatment of AAT attenuated the deterioration of oxygenation, the
      reduction of compliance and the deterioration of other physiological and
      biochemical parameters mentioned above. CONCLUSION: Pretreatment with AAT could
      attenuate endotoxin-induced lung injury in rabbits. Those beneficial effects of
      AAT might be due, in part, to reduction in the levels of mediators that could
      activate neutrophils, in addition to the direct inhibitory effect on neutrophil
      elastase.

PMID- 14642135
TI  - Triclabendazole in the treatment of Paragonimiasis skrjabini.
AB  - OBJECTIVE: To observe triclabendazole effect on Paragonimus skrjabini in
      experimentally infected rats,and to develop a new drug for treating
      paragonimiasis. METHODS: Metacercariae of Paragonimus skrjabini were isolated
      from crabs (Sinopotamon) collected from endemic area. Wistar rats were infected
      intraperitoneally. One and two months after infection, they were treated with
      triclabendazole at the dosage of 300 mg.kg(-1).2 d(-1), 450 mg.kg(-1).3 d(-1) and
      600 mg.kg(-1).3 d(-1) respectively. Five patients with Paragonimus skrjabini were
      treated, with Triclabendazole dosage of 10 mg/kg bid x 3 days. RESULTS: The worm
      reduction rates were 50.3%, 80.8% and 86.7% respectively one month after
      completion of treatment. Dead worms of sesame size recovered from muscles, liver,
      abdominal cavity, chest cavity and lung were greatly diminished in size and
      weight in comparison with that of the control group. Many large (about 1 cm)
      black-colored distended worm cysts were found in the lungs of the control rats.
      Usually there were two adult worms pairs with numerous eggs in each worm cyst.
      Most worm cysts in the treated groups of rats were changed into hemorrhagic
      necrotic patches. All five patients were cured. CONCLUSION: Triclabendazole was
      highly active against Paragonimus skrjabini in rats experimentally infected and
      patients.

PMID- 14642137
TI  - The role of prourokinase gene in protecting vein grafts from intimal hyperplasia.
AB  - OBJECTIVE: To study the duration of prourokinase gene expression in vein grafts
      and the role of the prourokinase gene in protecting vein grafts from neointimal
      hyperplasia. METHODS: Fifty-four Wistar rats were used in this study. In each
      rat, the jugular vein was excised and distended for 30 minutes using a solution
      containing either Adv(5)-CMV (control group) or Adv(5)-CMV/Pro-UK (treatment
      group). Next, the jugular vein was reversed and interposed into the divided
      carotid artery of the same rat. On the 14th day after transfection, vein grafts
      of the control group were collected in order to perform a fibrinolysis test for
      prourokinase (Pro-UK) activity. On the 2nd, 7th, 14th, 28th, and 60th day, the
      vein grafts of the treatment group were likewise collected in order to detect
      prourokinase activity. On the 28th day, the vein grafts of both groups were
      explanted to evaluate the (3)H-TDR incorporation so that pathologic analysis
      could be performed. RESULTS: Pro-UK activity could not be detected in the control
      group, while in the treatment group, the Pro-UK activity could be detected from
      the 2nd day onwards, peaking on the 7th day and declining from the 14th day, but
      yet persisting at a low level for a further month. The amount of (3)H-TDR
      incorporated in the control group was higher than that in the treatment group.
      Pathologic analysis demonstrated that vein grafts of both groups exhibited wall
      thickening, but that the degree of graft neointimal hyperplasia and reduction of
      the graft lumen was greater in the control group than that in the treatment
      group. The occlusion rate of grafts in the control group was 20%. All grafts in
      the treatment group were patent. CONCLUSIONS: Pro-UK gene transfer before vein
      grafting in vitro results in a high level of gene expression in the vein graft
      from the 7th day to 14th day. And its gene expression in the vein graft could
      reduce neointimal hyperplasia in the vein graft.

PMID- 14642139
TI  - Effects of BmkTXK beta on electrophysiological properties of rabbit atrial
      myocytes.
AB  - OBJECTIVE: To investigate the effects of BmkTXK(beta), a newly purified 'long
      chain' peptide inhibitor of K(+) channels from the Chinese scorpion Buthus
      martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit
      atrial myocytes. METHODS: The standard whole-cell patch-clamp technique was used
      to study the effects of multiple concentrations of BmkTXK(beta) on potassium
      currents and action potentials. RESULTS: BmkTXK(beta) produced concentration
      dependent prolongation of action potential duration at 20%, 50%, and 90%
      repolarization (APD(20,50,90)) without any use-dependence. Meanwhile, it had no
      significant effect on RMP, APA, or V(max) (n = 9). At a dose of 1 micro mol/L,
      BmkTXK(beta) decreased I(to) by 41.4% (n = 10, P < 0.01) at a membrane potential
      of +50 mV [from (13.63 +/- 0.87) pA/pF to (7.98 +/- 0.78) pA/pF]. I(to) was
      reduced significantly with an IC(50) value of 1.82 micromol/L (95% confidence
      interval: 1.47 - 2.17 micro mol/L), in a clear concentration-dependent manner.
      BmkTXK(beta) blocked I(Ks) and I(Ks),tail with an IC(50) of 20.15 micromol/L and
      a 95% confidence interval of 16.93 - 23.37 micromol/L. At a concentration of 10
      micromol/L, BmkTXK(beta) blocked both I(Ks) (mean reduction 37.3% +/- 4.2%, P <
      0.01, n = 7) and I(Ks), tail (mean reduction 35.8% +/- 4.1%, P < 0.01, n = 7). At
      0 mV, 10 micromol/L BmkTXK(beta) inhibited both I(Kr) (mean reduction 40.5% +/-
      2.6%, P < 0.01, n = 6) and I(Kr), tail (mean reduction 42.3% +/- 2.9%, P < 0.01,
      n = 6). Blocking of I(Kr) by BmkTXK(beta) occurred in a concentration-dependent
      manner, with an IC(50) of 17.21 micromol/L (95% confidence interval: 14.76-19.66
      micromol/L). An absence of effects on I(K1) was observed for BmkTXK(beta), with
      no change in reversal-potential (n = 6, P > 0.05). CONCLUSIONS: BmkTXK(beta)
      exerts direct blocking effects on several potassium channels involved in cardiac
      repolarization, and has a strong effect on prolonging the repolarization of
      rabbit cardiomyocytes without reverse frequency dependence. This finding suggests
      that BmkTXK(beta) could be a promising class III drug for anti-arrhythmic therapy
      without the risk of proarrhythmia.

PMID- 14642140
TI  - Effects of thyroxine on cardiac function and lymphocyte beta-adrenoceptors in
      patients with chronic congestive heart failure.
AB  - OBJECTIVE: To explore the effects of thyroid hormone (TH) on cardiac function and
      peripheral lymphocyte beta-adrenoceptors (beta-ARs) of patients with chronic
      congestive heart failure (CHF). METHODS: Twenty-eight patients with class III or
      IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy
      (ICM) were randomly divided into groups A and B. L-thyroxine (L-T(50)) was
      administered to group B. Exercise tolerance, chest X-rays, and echocardiographic
      parameters were obtained before and after one month of treatment, Ficoll-hypaque
      solution was used to separate peripheral lymphocytes, and (125)I-pindolol
      radioligand binding was used to measure beta-AR levels in peripheral lymphocytes.
      RESULTS: L-T(50) therapy improved cardiac output [CO, (2.98 +/- 0.31)L/min vs
      (3.24 +/- 0.28) L/min, P < 0.01], left ventricular ejection fraction (LVEF,
      26.21% +/- 3.21% vs 37.93% +/- 9.01%, P < 0.01), and decreased isovolumetric
      relaxation time (IVRT, 0.12 +/- 0.04 vs 0.10 +/- 0.02, P < 0.01). Serum TH levels
      and the maximal number of beta-AR binding sites (beta(max)) in peripheral
      lymphocytes were lower in patients with CHF than in normal healthy people, but L
      T(50) administration induced a beta-AR up-regulation on peripheral lymphocyte
      surfaces. L-T(50) was well tolerated without episodes of ischemia or arrhythmia.
      There was no significant change in heart rate or metabolic rate. CONCLUSION: TH
      administration improves cardiac function and beta-AR expression in peripheral
      lymphocytes of patients with CHF.

PMID- 14642141
TI  - Linkage analysis of five Chinese families with arrhythmogenic right ventricular
      cardiomyopathy using microsatellite genetic markers.
AB  - OBJECTIVE: To explore the linkage relationship between specific genetic markers
      and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees.
      METHODS: The microsatellite genetic markers D2S152, D14S252, and D10S1664 were
      studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal
      population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal
      population was amplified using PCR techniques. Denaturing polyacrylamide
      sequencing gel (4%) electrophoresis was used to detect microsatellite repeat
      polymorphisms. Gels were silver-stained. A classical linkage analysis program was
      used assuming models of autosomal dominance and recession. RESULTS: The logarithm
      of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees
      were 2.174, -0.589, -infinity, - (indicating that linkage is not supported in
      this mode), and -infinity respectively in autosomal dominant model (recombination
      fraction = 0.000 respectively)and were -infinity, -infinity, -infinity, 
      infinity, and 0.182 respectively in the autosomal recessive model. The LOD scores
      of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -infinity, -,
      and 0 respectively in autosomal dominant model, and were -infinity, -0.812, 
      infinity, -infinity, and 0.087 respectively in autosomal recessive model. The LOD
      scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -,
      and 0.602 respectively in autosomal dominant model and were -, -infinity, 
      infinity, -infinity, and - infinity respectively in autosomal recessive model.
      CONCLUSIONS: The LOD score for D2S152 in the LW pedigree was 2.174, indicating
      that the chance of linkage is about 150:1. This suggests that there is a possible
      ARVC-related gene near this marker. There were no clear linkage relationships
      between ARVC and D10S1664 and D14S252 in this family, and no linkages between
      ARVC and any of the three genetic markers in the other four families. These
      results also suggest that there is genetic heterogeneity in LW and in the other
      pedigrees.

PMID- 14642142
TI  - Plasminogen activator inhibitor-1 4G/5G gene polymorphism in patients with
      myocardial or cerebrovascular infarction in Tianjin, China.
AB  - OBJECTIVE: To investigate the association between the plasminogen activator
      inhibitor-1 (PAI-1) 4G/5G gene polymorphism and the occurrence of myocardial and
      cerebrovascular infarctions in individuals from Tianjin, China. METHODS: The PAI
      1 genotype was determined using allele-specific polymerase chain reaction (AS
      PCR) in 56 myocardial infarction (MI) patients, 54 cerebrovascular infarction
      (CI) patients and 83 unrelated healthy controls. All subjects' clinical features
      and plasma PAI-1 activity levels were determined. RESULTS: The PAI-1 genotype
      distribution frequency of the single guanine deletion/insertion 4G/5G
      polymorphism (located -675 bp upstream from the start of transcription)
      significantly differed between the patients and healthy controls. In the MI
      group, the 4G/4G-genotype frequency was increased, but the 4G/5G-genotype is
      decreased when compared to the control group. In the CI group, both the 4G/4G-
      and 4G/5G -genotypes occurred at a lower frequency than those in the control
      group (P < 0.001). The plasma PAI-1 activity level in the MI group was lowered as
      the presence of the 4G allele decreases. In the CI group, the frequency of 5G/5G
      was much higher than that of the control group (P < 0.001). The plasma PAI-1
      activity level in the CI group was elevated as the presence of the 5G allele
      increased. Furthermore, positive correlation between triglyceride, glucose levels
      and PAI-1 activity were found in all three groups (P < 0.001). CONCLUSIONS: The
      PAI-1 4G/5G gene polymorphism is associated with a higher risk of MI and CI in
      individuals in Tianjin, China. The deletion/insertion polymorphism is probably an
      important hereditary risk factor for heart diseases. Moreover, triglyceride and
      glucose levels of plasma have functional importance in regulating PAI-1 activity.

PMID- 14642143
TI  - The effect of theophylline on sleep-disordered breathing in patients with stable
      chronic congestive heart failure.
AB  - OBJECTIVE: To determine the prevalence of sleep-disordered breathing in patients
      with stable, optimally treated chronic congestive heart failure and the effect of
      short-term oral theophylline therapy on periodic breathing in these patients.
      METHODS: Patients with stable, optimally treated chronic congestive heart failure
      were monitored by polysomnography during nocturnal sleep. The effects of
      theophylline therapy on periodic breathing associated with stable heart failure
      were observed before and after treatment. RESULTS: Patients were divided into two
      groups. Group I (n = 21) consisted of individuals with 15 episodes of apnea and
      hypopnea [as determined by the apnea-hypopnea index (AHI)] per hour or less;
      Group II (n = 15, 41.7%) individuals had an index of more than 15 episodes per
      hour. In group II, the AHI varied from 16.8 to 78.8 (42.6 +/- 15.5) in which the
      obstructive AHI was 11.1 +/- 8.4 and the central AHI was 31.5 +/- 9.6. Group II
      had significantly more arousals (36.8 +/- 21.3 compared with 19.4 +/- 11.2 in
      group I) that were directly attributable to episodes of apnea and hypopnea, lower
      arterial oxyhemoglobin saturation (76.7% +/- 4.6% compared with 86.5% +/- 2.8%)
      and lower left ventricular ejection fraction (24.2% +/- 8.8% compared with 31.5%
      +/- 10.6%). Thirteen patients with compensated heart failure and periodic
      breathing received theophylline orally (at an average dose of 4.3 mg/kg) for five
      to seven days. After treatment, the mean plasma theophylline concentration was
      (11.3 +/- 2.5) micro g/ml. Theophylline therapy resulted in significant decreases
      in the number of AHI (20.8 +/- 13.2 vs. 42.6 +/- 15.5; P < 0.001) and the number
      of episodes of central apnea-hypopnea per hour (10.1 +/- 7.6 vs. 31.5 +/- 9.6; P
      < 0.001). Furthermore, the percentage of total sleep time during which arterial
      oxyhemoglobin saturation (SaO(2)) was less than 90 percent (8.8% +/- 8.6% vs.
      23.4% +/- 24.1%; P < 0.05) and the arousals per hour (18.7 +/- 21.2 vs. 36.8 +/-
      21.3; P < 0.05) were also lower. There were no significant differences in the
      characteristics of sleep or obstructive AHI before and after theophylline
      treatment. CONCLUSIONS: The prevalence of sleep-disordered breathing (mainly
      periodic respiration or cheyne-stokes respiration with central sleep apnea) is
      high in patients with stable chronic congestive heart failure. The sleep
      disordered breathing episodes are associated with severe nocturnal arterial blood
      oxyhemoglobin desaturation and excessive arousals. In these patients, oral
      theophylline therapy may reduce the number of episodes of central apnea and
      hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal
      sleep.

PMID- 14642144
TI  - A comparative study of clinical manifestations caused by tuberculosis in
      immunocompromised and non-immunocompromised patients.
AB  - OBJECTIVE: To characterize the differences between clinical manifestations in
      immunocompromised patients (ICPs) and non-immunocompromised patients (non-ICPs)
      with tuberculosis. METHODS: Underlying diseases, clinical presentations,
      misdiagnosis, treatment and prognosis, etc, were analyzed retrospectively in 115
      tuberculosis patients, including 39 ICPs and 76 non-ICPs. RESULTS: Compared with
      non-ICPs, the individuals who were ICP had more expectoration (64.1% vs 35.5%),
      pulmonary moist rale (41.0% vs 9.2%), miliary pulmonary tuberculosis (30.8% vs
      2.6%), pleural effusion (48.7% vs 25.0%) and lymphadenopathy (18.0% vs 4.0%).
      ICPs had less lung cavity (15.4% vs 22.4%) and pleural thickening (15.4% vs
      23.7%) compared to non-ICPs. Pulmonary tuberculosis in ICPs was prone to be
      misdiagnosed as pneumonia (23.1% vs 6.6%). Pulmonary tuberculosis was found in
      the apicoposterior segment (SI + SII) in more cases in non-ICPs (21.7%, 10/46)
      than ICPs (10.3%, 3/29). The diagnostic value of tuberculin skin test and
      adenosine deaminase in pleural effusions was limited in ICPs. ICPs had
      significantly poorer prognoses than non-ICPs. CONCLUSION: The clinical
      manifestations of ICPs with tuberculosis are atypical, misdiagnosis often occurs,
      resulting in a worse prognosis.

PMID- 14642145
TI  - Diffuse panbronchiolitis complicated with thymoma: a report of 2 cases with
      literature review.
AB  - OBJECTIVE: Diffuse panbronchiolitis, a distinct clinical entity of unknown
      etiology, has been reported originally and primarily in Japanese and rarely in
      non-Japanese populations. Macrolide therapy is effective for this once dismal
      disease. Diffuse panbronchiolitis complicated with thymoma is uncommon; only 2
      cases have been reported to date. The aims of this study were to describe the
      clinical profiles, assess the response to macrolide therapy, and to discuss the
      possible pathogenesis of diffuse panbronchiolitis in this setting. METHODS: The
      clinical profiles, macrolide therapy response of diffuse panbronchiolitis
      complicated with encapsulated thymoma in 2 histologically confirmed cases were
      described and discussed with the 2 cases reported in the literature: one
      complicated with encapsulated thymoma, another with invasive thymoma. RESULTS: Of
      the 2 cases, both had negative PPD skin testing and abnormal serum levels of
      various immunoglobulins, 1 had positive anti-nuclear antibody, but none had
      elevated cold hemagglutinin titers, and both had an excellent response to
      macrolide therapy. Of the 2 cases reported in the literature, both had negative
      PPD or tuberculin skin testing, 1 had severe hypogammaglobulinemia, 1 had
      elevated IgA, 1 had positive anti-DNA, 1 had elevated cold hemagglutinin titers,
      but both died of respiratory failure in spite of macrolide therapy in 1 case.
      CONCLUSIONS: Prognosis for diffuse panbronchiolitis complicated with thymoma may
      depend on the nature of the thymoma and on the disease course. Macrolide therapy
      is also effective if administered early in the disease course and if the thymoma
      is cured. Immunological factors may play an important role in the pathogenesis of
      diffuse panbronchiolitis in this setting.

PMID- 14642146
TI  - Glutamic acid decarboxylase 65 autoantibody levels discriminate two subtypes of
      latent autoimmune diabetes in adults.
AB  - OBJECTIVE: To compare the clinical characteristics between type 2 diabetes
      mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) with different
      titers of glutamic acid decarboxylase autoantibody (GADA) and to define the two
      distinct subtypes of LADA. METHODS: Sera of 750 patients with an initial
      diagnosis of T2DM from central south of China were screened for GADA using a
      radioligand assay. The distribution and frequency of GADA levels were described.
      Two hundred and ninety-five patients were divided into the T2DM group (n = 233)
      and the LADA group (n = 62) to compare the age of onset, body mass index,
      HbA(1c), C-peptide, hypertension, dyslipidemia and chronic diabetic
      complications. Furthermore, LADA patients with different GADA titers were
      subdivided to analyze the same indexes as the above. RESULTS: The prevalence of
      LADA (defined as GADA > or = 0.05, namely GADA positive) was 9.7% in the 750
      initially diagnosed type 2 diabetic patients. Compared with T2DM, LADA patients
      were younger at their ages of onset, had lower C-peptide and body mass index, and
      also had less cases with hypertension and with dyslipidemia. However, only
      patients with high titer of GADA had poorer beta cell functions and less diabetic
      complications compared to T2DM and low GADA titer of LADA patients. Patients with
      low GADA titer were similar to T2DM patients, except that they were prone to
      develop ketosis more frequently. CONCLUSIONS: Two clinically distinct subtypes of
      LADA can be identified by GADA levels in patients initially-diagnosed as type 2
      diabetes. Patients with high titer of GADA (GADA > or = 0.5) subsequently develop
      more insulin dependency, which are classified as LADA-type 1; while those with
      lower GADA titer (0.05 < or = GADA < 0.5) and having clinical and metabolic
      phenotypes of type 2 diabetes are classified as LADA-type 2.

PMID- 14642147
TI  - Is the human dystrophin gene's intron structure related to its intron
      instability?
AB  - OBJECTIVE: To study the human dystrophin gene molecular deletion mechanism, we
      analyzed breakpoint regions within junction fragments of deletion-type patients
      and investigated whether the dystrophin gene's intron structure might be related
      to intron instability. METHODS: Junction fragments corresponding to exon 46 and
      51 deletions were cloned. The breakpoint regions were sequenced, and the features
      of introns with available Genebank sequences were analyzed. RESULTS: An analysis
      of junction fragment sequences corresponding to exon 46 and 51 deletions showed
      that all 5' and 3' breakpoints are located within repeat sequences. No small
      insertions, small deletions, or point mutations are located near the breakpoint
      junctions. By analyzing the secondary structure of the junction fragments, we
      demonstrated that all junction fragment breakpoints are located in non-matching
      regions of single-stranded hairpin loops. A high concentration of repetitive
      elements is found to be a key feature of many dystrophin introns. In total, 34.8%
      of the overall dystrophin intron sequences is composed of repeat sequences.
      CONCLUSION: Repeat elements in many dystrophin gene introns are the key to their
      structural bases and reflect intron instability. As a result of the primary DNA
      sequences, single-stranded hairpin loops form, increasing the instability of the
      gene, and forming the base for breaks in the DNA. The formation of the single
      stranded hairpins can result in reattachment of two different breakpoints,
      producing a deletion.

PMID- 14642148
TI  - Clinical spectrum of diffuse crescentic glomerulonephritis in Chinese patients.
AB  - OBJECTIVE: To investigate retrospectively the incidence, distribution of primary
      disease and clinicopathologic characteristics of diffuse crescentic
      glomerulonephritis (DCGN) in Chinese patients. METHODS: One hundred and seventy
      two consecutive patients diagnosed as having DCGN out of 9828 cases of non
      transplanting renal biopsies over sixteen years, were studied. DCGN is
      categorized into three types according to immunopathologic characteristics. The
      incidence of this disease, its primary diseases, clinical characteristics and
      serum antineutrophil cytoplasmic antibodies (ANCAs) were analyzed. RESULTS: The
      distribution of patients among the three classifications was 8.7% type I, 68.6%
      type II and 22.7% type III. Clinically, the majority of patients (69.8%)
      presented rapidly progressive glomerulonephritis (RPGN), but 30.2% manifested a
      chronic nephritic syndrome or chronic renal failure. In terms of related
      conditions, 93% were anemic, 61.6% had hypertension, 50.6% oliguria, 45.3%
      nephrotic syndrome, 43% uremic syndrome and 39.5% displayed gross hematuria.
      Those patients who were positive in serum for ANCAs had predominantly type III
      DCGN. Two cases with anti-GBM-antibody crescentic glomerulonephritis and three
      with lupus nephritis were also positive for ANCAs in serum. CONCLUSION: DCGN is
      not rare in Chinese patients. A majority of patients in our study presented with
      RPGN, but 30.2% manifested a chronic renal failure. Lupus patients with DCGN that
      were positive for ANCAs had more severe vasculitic lesions.

PMID- 14642149
TI  - Impact of acute rejection episodes on long-term renal allograft survival.
AB  - OBJECTIVE: To assess the impact of the number, and time of acute rejection (AR)
      and outcome of anti-rejection therapy on the long-term survival of renal
      allografts and the relative risk factors. METHODS: The Kaplan-Meier analysis and
      log-rank test were used to calculate the survival rates of patients and grafts in
      no acute rejection group (NAR, 895 patients), 1 rejection episode group (1AR,
      183), 2 and more than 2 rejection episodes group (2AR, 17), acute rejection group
      [AR (1AR + 2AR), 200], early acute rejection group (within 90 days after
      transplantation, EAR, 125), late acute rejection group (91 days later, LAR, 58),
      completely AR reversed group (CAR, 105), and incompletely AR reversed group (IAR,
      68). The relative risk factors were analyzed by the Cox proportional hazards
      regression. RESULTS: The 5- and 10-year survival rates of renal allografts were
      75.4% and 17.1% in AR and 93.2% and 86.5% in the NAR group (P < 0.0001). The long
      term graft survival was much lower in the 2AR group than in the NAR or 1AR groups
      (P < 0.0001 and P = 0.002, respectively). It was similar in either the NAR or CAR
      groups (P = 0.31), but it was significantly lower (P < 0.0001) in the IAR group.
      Multivariate Cox regression analysis revealed that the outcome of anti-rejection
      therapy is an important risk factor affecting the long-term survival of
      allografts. CONCLUSIONS: AR is significantly associated with poor long-term
      survival of renal allografts. But the long-term graft survival of patients with
      one acute rejection but completely reversed is not significantly different from
      that of patients without acute rejection.

PMID- 14642150
TI  - Retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria.
AB  - OBJECTIVE: To report our experiences in retroperitoneoscopic renal pedicle
      lymphatic stripping for chyluria. METHODS: Six cases of filarial chyluria were
      admitted to our hospital from November 2001 to June 2002. Of these cases, 4 were
      men and 2 women, with age ranging from 34 to 52 years (mean, 42 years). Diagnosis
      was made by using urine test for the presence of chyle and fat globule,
      cystoscopy, excretory urogram and retrograde pyelography. Chyluria was found on
      the left renal unit in 2 cases and on the right side in 4 cases. The technique of
      retroperitoneoscopic management of chyluria consisted of nephrolympholysis, hilar
      vessel stripping and ureterolympholysis. RESULTS: Operative time ranged from 69
      to 120 minutes (mean, 95 minutes). Intraoperative blood loss was 50-180 ml (mean,
      85 ml). Chyluria disappeared in all patients immediately after operation. Mild
      hematuria occurred in 4 cases within 12 hours and disappeared at 24 hours.
      Subcutaneous emphysema around the lesions was found in 2 cases and was
      spontaneously absorbed 3 days after the treatment. There was no lymphatic leak at
      the lesions. The patients were discharged from the hospital 5-9 days after the
      treatment. All patients gained weight and their haemoglobin and serum protein
      increased by 13.5 g/L and 3.66 g/L respectively. No chyluria recurrence was
      reported during 1-1.6 years follow-up. CONCLUSIONS: Retroperitoneoscopic renal
      pedicle lymphatic disconnection for chyluria is a safe, effective and efficient
      surgical procedure with minimal invasion, less pain, lower morbidity, short
      hospital stay and rapid recovery.

PMID- 14642151
TI  - Clinical investigation on gastric oxalate absorption.
AB  - OBJECTIVE: To study the stomach role in exogenous oxalate absorption. METHODS:
      The kinetic variation of urinary oxalate excretion (mg/min) in 10 healthy adults
      and 8 patients who underwent total gastrectomy was investigated before and after
      an oral spinach oxalate load. The bioavailability of the oxalate load in the
      healthy adults was calculated and compared with that in the patients. RESULTS:
      The oxalate content in the oral spinach load was 2567-2670 mg. The urinary
      oxalate excretion (mg/min) in the 10 healthy adults increased significantly 20
      minutes after loading (this increase was compared against their basic oxalate
      excretion level of 0.0331 +/- 0.0203). Further observations after loading
      include: a first peak of oxalate excretion 40 minutes after loading; an oxalate
      excretion level double that of the basic level after 60 minutes (0.0732 +/-
      0.0294) and a second peak appearing at 3 hours (P < 0.01). A "first peak" (0.063%
      +/- 0.062%) was not in any of the patients who underwent a total gastrectomy.
      Furthermore, a bioavailability of oxalate, which was 50% lower than that in the
      healthy subjects, appeared 60 minutes after loading (0.098% +/- 0.071%, P <
      0.01). CONCLUSIONS: The stomach is a powerful oxalate absorption organ under
      normal physiological conditions. Further investigation on the relationship
      between stomach dysfunction and urinary calcium oxalate formation is needed.

PMID- 14642152
TI  - Patient controlled intravenous analgesia with tramadol for labor pain relief.
AB  - OBJECTIVE: To evaluate the safety and analgesic efficacy of patient controlled
      intravenous analgesia (PCIA) with tramadol, and to compare its benefits and risks
      with combined spinal-epidural analgesia (CSEA)+ patient controlled epidural
      analgesia (PCEA). METHODS: Eighty American Society of Anesthesiologist (ASA) I-II
      at term parturients in active labor were randomly divided into 3 groups: the
      control group (n = 30) received no analgesia; group A (n = 30) received spinal
      administration with ropivacaine 2.5 mg and fentanyl 5 microg, then with PCEA;
      group B (n = 20) received 1 mg/kg tramadol loading dose i.v. PCIA with 0.75%
      tramadol and it included: PCA dose 2 ml, lockout time 10 minutes, background
      infusion 2 ml/h, total dose no more than 400 mg. The intensity of pain was
      evaluated using Visual Analogue Scale (VAS). RESULTS: Both group A and B showed
      good pain relief. VAS pain scores were significantly decreased in group A and B
      compared with those in the control group (P < 0.01). In comparison with group B,
      the VAS pain scores decreased in group A (P < 0.05). The onset times of analgesia
      in group A were shorter than those in group B (P < 0.05). Apgar scores in group B
      were lower than those in group A (P < 0.05). The periods of second stage of labor
      in group A were longer than those in the control group and group B (P < 0.05).
      The cesarean delivery rate was significantly higher in the control group (16.7%)
      than in group A (3.3%) and group B (5.0%), but it did not differ between group A
      and B. There were no significant differences in vital signs, fetal heart rate,
      degree of motor block, and uterine contractions among the 3 groups. CONCLUSIONS:
      PCIA with tramadol is now a useful alternative when patients are not candidates
      for CSEA for labor, or do not want to have a neuraxial block anesthesia. However,
      sometimes it may not provide satisfactory analgesic effect.

PMID- 14642153
TI  - IL-10 polymorphism is associated with increased incidence of severe sepsis.
AB  - OBJECTIVE: To investigate whether three biallelic polymorphisms at positions 
      592, -819 and -1082 in the promoter region of the IL-10 gene are associated with
      increased incidence of severe sepsis. METHODS: The IL-10 -592, -819 and -1082
      polymorphisms were typed using polymerase chain reaction followed by digestion
      with the restriction enzymes RsaI, MaeIII and MnlI, respectively. RESULTS:
      Patients with severe sepsis were more likely to have IL-10 -1082 allele 1,
      compared with controls (P < 0.05). Genotype distribution of the IL-10 -1082
      polymorphism significantly differed between patients and controls (P < 0.05).
      However, the allele frequencies and genotype distribution of the IL-10 -1082
      polymorphism did not differ between surviving and dead patients (P > 0.05). No
      significant differences in the genotype distribution and allele frequencies of
      the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with
      severe sepsis and healthy controls, nor between surviving and dead patients (P >
      0.05). CONCLUSIONS: The polymorphism at position -1082 in the promoter region of
      the IL-10 gene may be associated with susceptibility to severe sepsis. In
      contrast, the other two highly linked IL-10 polymorphisms are not associated with
      incidence or the outcome of severe sepsis.

PMID- 14642154
TI  - Advances in antithrombin therapy for ST-elevation myocardial infarction.
AB  - Thrombin is a pivotal molecule in acute myocardial infarction (MI) because of its
      extensive procoagulant and prothrombotic actions. Antithrombin therapy is an
      important component of the pharmacotherapy for acute MI. The standard agent used
      in clinical practice, unfractionated heparin (UFH), is associated with the
      disadvantages of variable anticoagulant effect, inability to inhibit clot-bound
      thrombin, neutralization by platelet factor 4, and the propensity to cause
      thrombocytopenic complications. Novel thrombin inhibitors have been developed to
      overcome these disadvantages. Although possessing the property of inhibiting both
      fluid-phase and clot-bound thrombin, the direct thrombin inhibitor hirudin has
      been shown to give marginal benefits over UFH as adjunct to fibrinolysis in ST
      elevation MI. Bivalirudin, another direct thrombin inhibitor, is able to reduce
      reinfarction in patients treated with streptokinase and is a new anticoagulant
      treatment option in this setting. The pharmacokinetic characteristics of better
      availability, longer half-life, and dose-independent clearance together with the
      ability of inhibiting both thrombin generation and activity make the low
      molecular-weight heparins (LMWHs) an attractive alternative to UFH. The favorable
      benefit/risk profile of the LMWHs as adjunct to different generations of
      fibrinolytic agents is setting the stage for larger clinical trials to confirm
      their role as the antithrombin agent of choice for STEMI.

PMID- 14642155
TI  - The effect of arsenic trioxide on QT interval prolongation during APL therapy.
AB  - OBJECTIVE: To investigate the cardiac effect of QT interval prolongation in the
      treatment of acute promyelocytic leukemia (APL) with arsenic trioxide
      (As(2)O(3)), and the relationship between QT and serum arsenic concentration.
      METHODS: Blood serum arsenic concentrations of thirty APL patients were
      determined at 2 hours, 4 hours, 8 hours, and 24 hours after As(2)O(3) injection
      using atomic fluorophotometry. Cardiac functions were measured simultaneously
      using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually
      measured, and then corrected using Bazett's formula (QTc). QT dispersion (QTd)
      was also calculated. In order to assess the effects of arsenic on the symptoms of
      anemia, twenty-four anemia patients were divided into two groups on the basis
      hemoglobin concentration: Group 1 (Hb > or = 90 g/L), and Group 2 (60 g/L < or =
      Hb < 90 g/L). QTc and QTd of these patients were also manually measured. RESULTS:
      All QT intervals of APL patients treated with As(2)O(3) injection were prolonged
      [32.2 ms (27, 41 ms); P < 0.05], but the changes of QTd were not prominent [3 ms
      (-8, 7 ms), P > 0.05]. There was a delay of 2 hours in maximum QTc following
      peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic
      groups were not prominent. CONCLUSIONS: As(2)O(3) can prolong QTc intervals in
      APL patients, but the effects are delayed compared to peak serum arsenic
      concentrations. As(2)O(3) has no prolongation effect on QTd. Mild and moderate
      anemia do not effect QTc and QTd.

PMID- 14642156
TI  - Effect of micronized fenofibrate on vascular endothelial function in patients
      with hypertriglyceridemia.
AB  - OBJECTIVE: To investigate the effect of micronized fenofibrate on vascular
      endothelial function in patients with hypertriglyceridemia. METHODS: Using high
      resolution ultrasound, we measured flow- and nitroglycerin-induced dilatation of
      the brachial artery in 30 patients with hypertriglyceridemia before and after
      treatment with micronized fenofibrate at a dose of 200 mg once daily for 4 weeks.
      Simultaneously, both serum lipid and plasma endothelin (ET) levels were
      determined. RESULTS: After micronized fenofibrate therapy, serum triglyceride
      (TG) levels decreased significantly (P < 0.05). Plasma ET levels also decreased
      markedly [(82.66 +/- 15.46) microg/L vs. (106.22 +/- 19.16) microg/L, P < 0.001].
      Flow-induced vasodilatation was much improved (11.0% +/- 9.0% vs 2.7% +/- 2.0%, P
      < 0.01). However, no significant changes in vasodilatation occurred in response
      to nitroglycerin (16.2% +/- 6.0% vs 15.0% +/- 5.0%, P > 0.05) in patients with
      hypertriglyceridemia. CONCLUSIONS: Micronized fenofibrate can improve impaired
      endothelium-dependent vasodilatation in patients with hypertriglyceridemia.
      Improving endothelial function may also be the mechanism responsible for the
      beneficial effects of micronized fenofibrate.

PMID- 14642157
TI  - Evaluation of transisthmus conduction interval in predicting bidirectional block
      after ablation of typical atrial flutter.
AB  - OBJECTIVE: To determine whether the extent of prolongation of the transisthmus
      interval after ablation predicts complete bidirectional block. METHODS: Since
      1996 to 2002, 30 consecutive patients underwent ablation procedures for isthmus
      dependent atrial flutter. There were 23 males and 7 females [mean age (47.85 +/-
      9.35) years]. With the use of fluoroscopic view of anatomy, radiofrequency
      ablation was performed during coronary sinus pacing at a cycle length of 600 ms.
      RESULTS: Bidirectional block was achieved with ablation in 29 (97%) of 30
      patients. The transisthmus intervals before ablation and after complete
      transisthmus block were (73.82 +/- 13.01) ms and (140.47 +/- 20.48) ms,
      respectively, in the clockwise direction (P < 0.0001), and (77.63 +/- 8.36) ms
      and (138.17 +/- 15.55) ms, respectively, in the counterclockwise direction (P <
      0.0001). A period of incomplete isthmus block was observed during 17 (58%) of the
      29 ablation procedures. The clockwise transisthmus intervals during incomplete
      block [(107.65 +/- 21.33) ms] were (45.5 +/- 8.7)% longer than the baseline
      transisthmus intervals. An increase in the transisthmus interval by > or = 50% in
      both directions after ablation predicted complete bidirectional block with 100.0%
      sensitivity and 83.3% specificity. The positive and negative predictive values
      were 90.6% and 100.0%, respectively. The diagnostic accuracy of a > or = 50%
      prolongation in the transisthmus interval was 83.3%. CONCLUSION: The analysis of
      transisthmus interval is a valuable method for determining complete bidirectional
      isthmus block.

PMID- 14642158
TI  - Molecular diagnosis of Down's syndrome.
AB  - OBJECTIVE: To establish a new diagnostic method for Down's syndrome using
      polymerase chain reaction (PCR). METHODS: DNA extracted from five healthy
      individuals and five Down's syndrome patients was amplified in six specific
      tetranucleotide repeat loci on chromosome 21 using PCR. An accurate diagnosis was
      made by analyzing allelic distribution at each locus. RESULTS: All Down's
      syndrome patients were identified as having at least two loci with three alleles,
      while none of the healthy individuals had three alleles. In addition, when two
      alleles were identified for a particular locus in the Down's syndrome samples, it
      was more likely that the intensity ratio between the two alleles was close to
      2:1. CONCLUSION: The molecular method can provide a fast, accurate, and
      economical alternation for the traditional cytogenetic diagnostic method for
      Down's syndrome.

PMID- 14642159
TI  - Protective effects of vitamin B12, ginseng saponin, and folic acid against murine
      fetal deformities caused by hyperthermia.
AB  - OBJECTIVE: To investigate the protective effects of vitamin B(12), ginseng
      saponin, and folic acid on mouse embryos subjected to high heat. METHODS: Mice
      were used for the experiment. RESULTS: After exposure of pregnant mice to high
      heat, the rates of teratism, stillbirth, and fetal absorption were markedly lower
      in mice treated with ginseng saponin and folic acid following heat exposure than
      in untreated mice. There were no significant differences in these rates when
      comparing mice treated with vitamin B(12) with the untreated mice. CONCLUSIONS:
      Ginseng saponin and folic acid can lessen injuries to murine embryos caused by
      high heat, while vitamin B(12) has little protective effect against high
      temperature except for promoting overall embryonic growth.

PMID- 14642160
TI  - The relationship between tumor necrosis factor-alpha gene polymorphisms and acute
      severe pancreatitis.
AB  - OBJECTIVE: To investigate the relationship between the presence of the TNF2
      allele and plasma concentrations of tumor necrosis factor-alpha (TNF alpha) and
      soluble TNF receptor (sTNF-R) with the development of acute severe pancreatitis
      (ASP) and severe sepsis. METHODS: Genomic DNA was prepared from peripheral blood
      leukocytes. The TNF1 and TNF2 biallelic polymorphisms were identified by
      analyzing NcoI-digested DNA fragments obtained from PCR products. Plasma levels
      of TNF alpha and sTNF-R were measured by EASIA. RESULTS: The overall TNF2 allele
      frequency in ASP patients was comparable to that found in healthy volunteers
      (29.2% vs. 29.3%, P > 0.05). Severe sepsis occurred in 26 of 72 patients.
      Patients with severe sepsis showed a significantly higher prevalence of TNF2 than
      those without (46.2% vs. 19.6%, P < 0.05). Plasma TNF alpha, sTNF-R I, and sTNF-R
      II levels were (36 +/- 31) pg/ml, (5.4 +/- 3.5) ng/ml, and (11.2 +/- 7.8) ng/ml,
      respectively, in patients with severe sepsis, and (31 +/- 25) pg/ml, (4.6 +/-
      3.8) ng/ml, and (8.8 +/- 6.6) ng/ml in non-severe sepsis subjects. Differences in
      TNF levels were not statistically significant between patients with ASP and
      control group (P > 0.05). Moreover, there was no correlation between TNF2 allele
      frequency and TNFalpha levels [(37 +/- 31) pg/ml vs. (31 +/- 25) pg/ml in TNF2
      group and TNF1 group, respectively, P > 0.05]. CONCLUSIONS: Our results suggest
      that there is no relationship between ASP and the TNF2 allele, but that the TNF2
      allele is associated with a susceptibility to severe sepsis as a result of ASP.

PMID- 14642161
TI  - Treatment of six cases of left renal nutcracker phenomenon: surgery and
      endografting.
AB  - OBJECTIVE: A retrospective study was undertaken to examine therapeutic strategies
      used in 6 patients with left renal venal nutcracker phenomenon. METHODS: Three
      patients underwent surgical transposition of the superior mesenteric artery.
      Three patients underwent endograft stent implantations with intervention.
      RESULTS: All 6 cases were completely relieved of left renal vein compression
      after the operations, leading to improved clinical symptoms and normal urine
      tests. CONCLUSIONS: Transposition of the superior mesenteric artery is a feasible
      method, but leads to complications and great trauma. Treating left renal venal
      nutcracker phenomenon with endografting techniques is minimally invasive in
      certain cases, and seems to have a prospective future.

PMID- 14642162
TI  - Pituitary involvement in Wegener's granulomatosis: a case report and review of
      the literature.

PMID- 14642163
TI  - Juxtaglomerular cell tumor of the kidney: a clinicopathological analysis of five
      cases.

PMID- 14642164
TI  - [Study on the gene mutation of TIGR in primary open angle glaucoma, their
      relatives and normal controls in Chongqing].
AB  - OBJECTIVE: To study trabecular meshwork induced glucocorticoid response protein
      (TIGR) gene mutation in primary open angle glaucoma (POAG), their relatives and
      normal controls in Chongqing. METHODS: (1) The coding sequence of TIGR was
      screened for sequence alterations using polymerase chain reaction (PCR) followed
      by single-strand conformation polymorphism (SSCP). (2) Samples corresponding to
      bands of altered mobility were sequenced. (3) The sequence alterations were
      analyzed by bioinformatics. RESULTS: (1) In 15 POAG, TIGR gene mutation was found
      in 5 cases. In 10 POAG relatives, 2 TIGR gene mutations were found. No TIGR gene
      mutation was found in 20 normal persons in Chongqing. (2) The mutation sites
      Ser55Thr, Asp247Stop and in 49021 c-t alteration discovered in the present study
      have not been reported previously. The 63155 c-t alternation has been reported as
      a polymorphism site previously. (3) Bioinformatics analysis indicated that the
      mutations in structural domain could lead to the changes in the amino acid
      sequence coded, second structure of protein, isoelectric point and antigen
      binding site. CONCLUSIONS: We found that the TIGR gene mutations is closely
      related to the occurrence of JOAG in Chongqing. The relatives of POAG patients
      may have a higher incidence of TIGR gene mutation as compared with the controls.
      Furthermore, after analyzed by bioinformatics, we found that the alteration of
      structure and biological activity of TIGR protein resulted from gene mutation may
      be one of the important changes that leading to the occurrence of POAG.

PMID- 14642165
TI  - [Pathological study on the deep scleral flap and external trabecular membrane
      obtained from non-penetrating trabecular surgery].
AB  - OBJECTIVE: To study the anatomic background of non-penetrating trabecular surgery
      (NPTS) and to explore the resistant site of aqueous outflow in primary open-angle
      glaucoma. METHODS: NPTS was performed in 18 eyes of 12 cases (10 males, 2
      females) with POAG. The age of these patients ranged from 42 to 65 years old. The
      deep scleral flap and external trabecular membrane were obtained during the
      surgical procedure and were examined by light microscope, scanning electron
      microscope (SEM) and transmission electron microscope (TEM). RESULTS: The
      beginning part of the collection canal in the outer wall of the Schlemm's canal
      were very narrow, and there was electron dense material (so-called plaques)
      around the outer wall of the Schlemm's canal. The external trabecular membrane
      consisted of adjacent trabecular meshwork and part of the corneoscleral
      trabecular meshwork. The number of the trabecular cells was decreased and a large
      amount of electron dense materials were deposited in the adjacent trabecular
      meshwork. The holes of the corneoscleral trabecular meshwork was small and
      irregular. In the corneoscleral trabecular meshwork, the trabecular lamellae was
      thicken, the amount of elastic-like fibers was increased and the trabecular
      cells, especially the nucleus, were enlarged. In the advanced stage of POAG, a
      great amount of electron dense material was deposited in the corneoscleral
      trabecular meshwork and the inter-trabecular spaces was blocked. CONCLUSIONS: The
      deep scleral flap of NPTS contains the outer wall of Schlemm's canal and the
      external trabecular membrane, which consists of the inner wall of the Schlemm's
      canal, the adjacent trabecular meshwork and part of the corneoscleral trabecular
      meshwork. The main resistant site of aqueous outflow in POAG lies in the adjacent
      trabecular meshwork and in part of the corneoscleral trabecular meshwork. The
      outer wall of the Schlemm's canal is another important resistant site for aqueous
      outflow.

PMID- 14642166
TI  - [Treatment of open angle glaucoma with deep sclerectomy combined with laser
      trabecular puncture].
AB  - OBJECTIVE: To study the effect of deep sclerectomy combined with laser trabecular
      puncture for the treatment of open angle glaucoma (OAG). METHODS: Deep
      sclerectomy was performed in 32 eyes of 32 patients with moderate to advanced
      stages of OAG. After the exposure of external wall of Schlemm's canal and the
      remaining trabecula, the intraocular optic fiber of diode laser photocoagulator
      was directed to the trabecula-limbus near the anterior edge of the scleral spur.
      Two or three punctures, approximately 0.5 mm in diameter, were performed with
      laser beam under direct visualization until aqueous humor was extravasated
      slowly. The scleral flap was closed with one or two sutures. Postoperative
      observation included intraocular pressure (IOP), intraocular tissue reaction, the
      appearance of filtering bleb, gonioscopy and ultrasound biomicroscopy. The follow
      up period was 4 to 24 months (7.94 +/- 6.20) months. RESULTS: The anterior
      chamber was recovered shortly after the operation and the visual acuity remained
      the same in all eyes. At the end of follow-up period, the postoperative IOP
      (14.86 +/- 4.15) mm Hg was lower than the preoperative IOP (29.68 +/- 5.76) mm
      Hg, the difference was statistically significant (t = 7.415, P < 0.001). Diffuse
      and obvious filtering blebs were found in all eyes after the operation, including
      27 functional blebs and 5 blebs that disappeared 2 to 3 months later. Iris was
      burned slightly in 2 cases, pigment was released and appeared in the anterior
      chamber temporarily. No laser injury occurred in the cornea and the lens. High
      IOP was found in 2 cases after long-term follow-up and could be controlled by
      antiglaucoma medication. CONCLUSIONS: Deep sclerectomy with laser trabecular
      puncture can effectively reduce the IOP, without the occurrence of serious
      complications that commonly seen after the trabeculectomy. It is an effective
      surgical method for the treatment of OAG.

PMID- 14642167
TI  - [Study of agreement of optic nerve head topography parameters].
AB  - OBJECTIVE: To evaluate the interobserver and intraobserver agreement of
      parameters of optic nerve head by Heidelberg Retina Tomograph (HRT). METHODS:
      Optic nerve heads from 50 eyes (30 subjects) were imaged with the HRT. Three
      ophthalmologists majoring in glaucoma traced the disc margin with a contour line.
      One of these observers, repeatedly traced the disc margin with contour line in
      triplicate at three different times. Eleven topographic parameters of optic nerve
      head (including disc area, cup area, cup/disc area ratio, rim area, cup volume,
      rim volume, mean cup depth, maximum cup depth, cup shape measure, mean retinal
      nerve fiber layer thickness, sectional area of retinal nerve fiber layer) were
      analyzed with HRT software (version 2.01). Intraclass coefficients (ICC) and
      agreement of result estimation (kappa value) were calculated. RESULTS: The ICCs
      results among three observers on 12 parameters of optic nerve head topography
      were 0.976 - 0.999, which showed almost perfect agreement; and the kappa value
      were 0.649 approximately 0.767, which showed substantial agreement. The ICC of
      the same observer in different times were 0.983 approximately 0.999, which showed
      almost perfect agreement; and the Kappa values were 0.810 approximately 0.951,
      which showed substantial agreement. CONCLUSIONS: Tracing the optic nerve head
      with contour line on HRT image is substantial to almost perfect within both
      interobserver and intraobserver in experienced ophthalmologist. This procedure is
      suitable for clinical diagnosis and follow-up observation of glaucoma.

PMID- 14642168
TI  - [Trabeculectomy with amniotic membrane transplantation and combining suture lysis
      of scleral flap in complicated glaucoma].
AB  - OBJECTIVE: To study and evaluate the outcome of trabeculectomy with amniotic
      membrane transplantation combining suture lysis of scleral flap in complicated
      glaucoma. METHODS: This operation was performed in 48 patients (67 eyes) with
      complicated glaucoma. Amniotic membrane was implanted under the scleral flap and
      the conjunctival flap and combined with suture lysis for scleral flap to control
      the outflow of the aqueous humor. RESULTS: Follow-up period ranged from 5 to 38
      months (mean 19.5 months). The intraocular pressure (IOP) was lowered from (43.86
      +/- 7.12) mm Hg (preoperative IOP) to postoperative (19.63 +/- 2.57) mm Hg
      (postoperative IOP) in neovascular glaucoma (t = 4.96, P < 0.001); from (40.31 +/
      4.79) mm Hg to (18.09 +/- 2.21) mm Hg in glaucoma after IOL implant (t = 3.54, P
      < 0.05); from (37.94 +/- 5.63) mm Hg to (20.14 +/- 3.15) mm Hg in aphakic
      glaucoma (t = 5.12, P < 0.05); from (32.48 +/- 3.98) mm Hg to (16.54 +/- 1.84) mm
      Hg in juvenile glaucoma (t = 4.23, P < 0.01); from (36.01 +/- 4.13) mm Hg to
      (18.11 +/- 3.40) mm Hg in uveitic glaucoma (t = 4.47, P < 0.01); from (34.43 +/-
      5.28) mm Hg to (18.31 +/- 1.52) mm Hg in glaucoma after failure of conventional
      filtering operation (t = 2.05, P < 0.05). Statistical significant difference was
      found in the IOP before and after the operation. The rate of formation of
      functional bulb was 80.6%. There were no reject reaction and severe
      complications. CONCLUSION: Trabeculectomy with amniotic membrane transplantation
      combining suture lysis of scleral flap is a useful method in complicated
      glaucoma.

PMID- 14642169
TI  - [The neuroprotective effect of erigeron breviscapus (vant) hand-mazz on retinal
      ganglion cells after optic nerve crush injury].
AB  - OBJECTIVE: To investigate whether a Chinese herbal medicine, erigeron breviscapus
      (vant) hand-mazz (EBHM), can protect the retinal ganglion cells (RGC) damaged by
      calibrated optic nerve crush injury. METHODS: Forty-two Sprague-Dawley rats were
      randomly divided into two groups. Calibrated optic nerve crush injury model was
      induced in the right eyes by a special designed optic nerve clip. The left eyes
      served as a control. All 42 rats were randomly divided into 2 groups. Group A
      consisted of the rats with calibrated optic nerve crush injury and group B
      consisted of rats with calibrated optic nerve crush injury treated with EBHM. In
      group B, EBHM solution was given once after the crush injury. According to the
      time interval between the optic nerve crush and the sacrifice, both groups A and
      B were further divided into three subgroups (day 4, day 14 and day 21).
      Therefore, there were 7 rats in each subgroup. Three days before sacrifice, 3%
      fast blue was injected into superior colliculi bilaterally. The eyes were
      enucleated after the rat was sacrificed, and flat mounts of the retina from both
      eyes were prepared on a slide and observed under a fluorescence microscope. Four
      photos with 400 x magnification were taken from each of the four quadrants of the
      retina 1 mm away from the optic disc. The labeled RGC were counted by a
      computerized image analyzer. The labeled RGC rate was used for statistical
      analysis (the labeled RGC rate = number of RGC in injured eye/control eye x
      100%). RESULTS: In group A, the labeled RGC rate was (77.79 +/- 7.11)%, (63.76 +/
      3.79)% and (54.66 +/- 4.75)% on day 4, day 14 and day 21, respectively. In group
      B, the labeled RGC rate was (80.13 +/- 12.03)%, (78.17 +/- 9.19)% and (83.59 +/-
      12.61)% on day 4, day 14 and day 21, respectively. In group B, which was treated
      with EBHM after injury, the labeled RGC rate was significantly higher than that
      of group A on day 14 and day 21. CONCLUSIONS: In the experimental optic nerve
      crush model in rats, EBHM therapy can increase the survival rate of the RGC and
      can rescue and/or restore the injured RGC.

PMID- 14642170
TI  - [Use of indocyaine green staining technique for phacoemulsification in white
      cataract].
AB  - OBJECTIVE: To evaluate the efficiency and safety of indocyaine green (ICG)
      staining technique using in white cataract phacoemulsification. METHODS: In a
      prospective clinical study, 105 eyes with white senile cataract were divided into
      two groups: capsular-staining group using ICG (n = 55) and noncapsular-staining
      group (n = 50). The time for performing the circular continuous capsulorrhexis
      (CCC), the number of radial tears of anterior capsule, the number of the rupture
      of capsular bag and the incidence of IOL in-the-bag fixation during the operation
      were recorded. We also measured the intraocular pressure and observed the changes
      of corneal endothelial cells, the anterior chamber flare and the keratic
      precipitation before surgery, 1 day and 3 months after surgery, respectively. The
      results of these two groups were compared. The quantitative results were analyzed
      with two-tailed student's t-test, while the qualitative results were analyzed
      with chi-square test. RESULTS: In operations performed with ICG staining
      technique, the CCC could be performed more quickly, no radial tears of the
      anterior capsule or rupture of capsular bag occurred and all IOL could be fixed
      in the bag. No statistically significant difference could be detected in the
      occurrence of these four aforementioned changes between these two groups. None of
      these patients had an elevation of intraocular pressure. The anterior chamber
      flare, the corneal endothelial cell density, the percentage of hexagonal cells
      and the corneal thickness showed no statistically significant difference between
      these two groups before and after surgery. CONCLUSION: Indocyaine green dye
      staining is a safe and useful technique in the white cataract
      phacoemulsification. We suggested to use ICG staining technique in the white
      cataract phacoemulsification.

PMID- 14642171
TI  - [Study of bcl-X(L) protection on retinal photoreceptors from apoptosis in vitro].
AB  - OBJECTIVE: To assess the effect of bcl-X(L), an anti-apoptotic gene, on glutamate
      induced apoptosis in cultured retinal photoreceptors. METHODS: Glutamate-induced
      apoptosis in cultured retinal photoreceptors was established. The experiment was
      divided into three groups: control, glutamate treatment and rAd-gfp-bcl-X(L) +
      glutamate transfection group, the protection of bcl-X(L) on retinal
      photoreceptors from apoptosis was evaluated. 6.5 x 10(12) pfu/L rAd-gfp-bcl-X(L)
      were transfected into retinal photoreceptors in the rAd-gfp-bcl-X(L) + glutamate
      group 48 h before Glutamate-induced apoptosis was established. The positive
      photoreceptors with green fluorescence were identified under fluorescence
      microscopy. The expression of Bcl-X(2) protein in rAd-gfp-bcl-X(L) transfected
      and non-transfected neurons were assessed by immunohistochemistry assay. DNA
      fragment was detected by agarose gel electrophoresis. Nuclei were revealed by
      hoechst33258 staining. RESULTS: rAd-mediated gene delivery can transfect retinal
      photoreceptors effectively. Increased expression of Bcl-X(L) protein was
      demonstrated in the rAd-transfecting neurons. Transfection of bcl-X(L)
      significantly decreased the number of apoptotic retinal photoreceptors in vitro.
      CONCLUSION: Transfection of bcl-X(L) protects cultured retinal photoreceptors
      from apoptosis induced by glutamate. Transfection the gene of bcl-X(L) may be a
      potential gene therapy for retinal degenerative diseases.

PMID- 14642172
TI  - [Effects of supplementation of different kinds of iodine on the antioxidative
      ability of retina in iodine deficient rats].
AB  - OBJECTIVE: To study the effects of iodine supplementation (in different kinds and
      doses) on the antioxidative ability of retina in iodine deficient rats. METHODS:
      One hundred and twenty eight iodine deficient Wistar rats were randomly divided
      into four groups, normal dose of iodate, normal dose of iodide, high dose of
      iodate and high dose of iodide. Concentration of serum thyroid hormones,
      including total TT(3) and total TT(4), were estimated by radioimmunoassay. GSH
      Px, SOD, TAOC activities and MDA content in the retina were determined using
      biochemical methods in the 22nd week of iodine supplementation. RESULTS:
      Statistical analysis showed that a significant difference in TT(3) level of serum
      was observed between animals treated with different doses. Serum TT(3) level in
      the groups treated with high doses was significantly higher than those with
      normal doses. However, no statistical difference could be detected at TT(4) level
      between animals treated with different doses. Different kind of iodine did not
      affect the level of thyroid hormones. Statistical analysis showed that a
      difference in SOD activity of retina was observed between animals treated with
      different doses. SOD activity in the groups with normal doses was significantly
      higher than that in groups with larger doses. Retina TAOC activity was
      significantly higher in groups treated with iodide than that in groups of iodate.
      Although there was no statistical difference in GSH-Px activity between different
      groups, it showed the same tendency as the SOD and TAOC activities, i.e. GSH-Px
      activity in the groups of normal doses was higher than that in the groups of high
      doses. GSH-Px activity in groups of iodide was higher than that in the groups of
      iodate. There was no significant difference in MDA content among these four
      groups. CONCLUSIONS: Different iodine and doses have certain effects on the
      antioxidative ability of retina in iodine deficient rat. The rats supplemented
      potassium iodide at normal dose showed higher antioxidative ability of the retina
      than those of the others.

PMID- 14642173
TI  - [Experimental study on promoting the engraftment of hematopoietic stem/progenitor
      cell by all-trans retinoic acid].
AB  - OBJECTIVE: To explore the effect of all-trans retinoic acid (RA) on the
      engraftment of unrelated umbilical cord blood stem/progenitor cell
      transplantation (UCBT) in murine model. METHODS: 1 x 10(6) and 0.5 x 10(6)
      nucleated cells (NC) from C57BL/6 (H-2(b)) fetal and neonatal peripheral blood
      (FNPB) were separately transfused into lethally cyclophosphamide (380 mg/kg, ip)
      treated BALB/C (H-2(d)) recipients, 15 mg.kg(-1).d(-1) and 5 mg.kg(-1).d(-1) RA
      (15 mg and 5 mg RA) were administrated respectively 2 days before and after UCBT.
      Hematopoiesis and immune recovery, graft versus host disease (GVHD), engraftment
      and survival rates were then observed. RESULTS: Hematopoiesis and immune recovery
      occurred faster in RA treated than in untreated mice (P < 0.05). Acute GVHD was
      absent. The levels of engraftment were higher in both 15 mg and 5 mg RA treated
      mice than those in untreated controls (P < 0.05). In 1 x 10(6) NC transfused
      mice, 15 mg and 5 mg RA could significantly increased the 30 and 60 days survival
      rates from 41.67% (without RA) to 72.23% and 70.83%, respectively (P < 0.05). In
      0.5 x 10(6) cells transfused mice, 15 mg and 5 mg RA increased the survival rate
      from 14.29% (without RA) to 42.86% and 43.48%, respectively (P < 0.05), which
      were comparable to that of being transfused 1 x 10(6) cells without RA treatment
      (P > 0.05). CONCLUSION: RA enhances the engraftment of umbilical cord blood
      stem/progenitor cells in murine model for UCBT. This might provide an
      experimental evidence of RA in clinical UCBT.

PMID- 14642174
TI  - [Dynamic changes of cytokines in G-CSF mobilized peripheral blood].
AB  - OBJECTIVE: To investigate the level and significance of interleukin-8 (IL-8),
      soluble intercellular adhesion molecule (sICAM-1) and soluble vascular cell
      adhesion molecule-1 (sVCAM-1) in patients peripheral blood (PB) during
      mobilization for peripheral blood stem cells harvesting. METHODS: The levels of
      IL-8, sICAM-1 and sVCAM-1 in patients were dynamically assayed by ELISA during
      the mobilization procedure and the number of CD(34)(+) cell, white blood cell
      (WBC) and platelet (BPC) by flow cytometric analysis and hematometry
      respectively. Colony formation was assayed by using semisolid methycellulose
      culture. RESULTS: There was a significant increase in plasma levels of IL-8 and
      both adhesion molecules [IL-8 (247.4 +/- 84.2) microg/L (P < 0.01); sICAM-1
      (530.3 +/- 286.1) microg/L (P = 0.002 7); sVCAM-1 (575.3 +/- 350.4) microg/L (P =
      0.001 3)] during the mobilization process; furthermore, IL-8 and sVCAM-1
      concentration in the patient's plasma was paralleled to the numbers of CD(34)(+)
      cell, CFU-GM, WBC and BPC (P < 0.001). CONCLUSION: The levels of IL-8, sICAM-1
      and sVCAM-1 in the patient's plasma were correlated to the PB number of CD(34)(+)
      cells, CFU-GM, WBC and BPC during the mobilization process. It suggested that
      analysis of IL-8, and sVCAM-1 dynamic changes may serve as markers for CD(34)(+)
      cells.

PMID- 14642175
TI  - [Experimental study on blocking immune escape of leukemia cells in the recipient
      after bone marrow transplantation].
AB  - OBJECTIVE: To investigate whether murine soluble Fas gene transfected marrow
      graft could block the immune escape of leukemia cells, so as to eliminate the
      residual leukemia cells and reduce relapse after bone marrow transplantation
      (BMT). METHODS: The murine leukemia/lymphoma models were established by
      inoculating female C57BL/6 mice (H-2b) with 10(5) EL4 cells/mouse through caudal
      vein. Donors of BM grafts were C57BL/6 male mice. Bone marrow mononuclear cells
      (BMMCs) were transfected with sFas or EGFP by adenovirus (adsFas or adEGFP) 24
      hours before BMT (group D or E). The following three groups were set
      simultaneously: group A, no BMMCs transplanted; group B, BMMCs transplanted with
      no adenoviruses transfection; group C, EL4 cells transfusion only. Hematopoietic
      reconstitution, generation of leukemia/lymphoma and the survival rate were
      observed in all the groups after BMT. RESULTS: The spleen indices examined 11
      days after BMT were not obviously different among group B, D and E (P > 0.05),
      but in group A were significantly lower than those in the groups B, D, E (P <
      0.01). The leukocyte and platelet counts on day 30 after BMT were recovered in
      group B and D, but were very low in group C and E. The Y-chromosomes appeared 2
      months after BMT. Bone marrow pictures in group B and D were almost normal, but
      in group C and E had plenty of lymphoblast-like tumor cells. Tumors were
      obviously revealed in the mice of group C and E by histopathology examination,
      but did not in group B and D. The survival rate was 0 in group A, 100% in group B
      and D, 12.5% in group C and 6.25% in group E. Compared with that in group E, the
      survival was significantly increased in the sFas group (P < 0.01). CONCLUSIONS:
      Graft transfected with sFas gene prolonged the post-BMT survival of
      leukemia/lymphoma mice. The transfection of sFas might block the effect of the
      immune escape of EL4 cells through FasL.

PMID- 14642176
TI  - [Detection of cytomegalovirus infection by polymerase chain reaction in
      hematopoietic stem cell transplantation recipients].
AB  - OBJECTIVE: To evaluate the detection of cytomegalovirus (CMV) by polymerase chain
      reaction (PCR) for predicting the development of CMV disease. METHODS: One
      hundred and thirty one allo-HSCT patients performed in the past 2 years were
      analyzed retrospectively. PCR-CMV was used to monitor CMV viremia and vireuria
      once a week after transplantation. RESULTS: In the dynamic detection, CMV viremia
      was positive for at least one chance in 89 patients, vireuria did in 99 patients.
      Thirty-seven patients developed CMV disease with an accumulative incidence of
      32.5%. The incidence of CMV disease was 15.6% in plasma CMV-PCR negative group,
      31.3% in positive once group, and 47.3% in positive over twice group. There was
      significant difference among the three groups (P = 0.0126). The incidence of CMV
      disease was 24.8% in urine CMV-PCR negative group, 43.5% in positive once group,
      and 33.0% in positive over twice group, being no significant difference among
      them (P = 0.845). On analysis, viremia could predict the development of CMV
      disease: the PPV (positive predictive value) is 40.5%, NPV (negative predictive
      value) is 84.4%, sensitivity is 75.0%, and specificity is 69.2%. CONCLUSIONS:
      Detected by CMV-PCR, MCV viremia may predict the development of CMV disease, but
      MCV vireuria cannot.

PMID- 14642177
TI  - [Seventeen cases of nonmyeloablative stem cell transplantation using a
      conditioning regimen containing fludarabine].
AB  - OBJECTIVE: To explore the efficiency and toxicity of non-myeloablative stem cell
      transplantation (NAST) for hematological disease. METHODS: Seventeen patients,
      including 3 acute myeloid leukemia, 6 chronic myelogenous leukemia, 4 severe
      aplastic anemia, 2 non-Hodgkin's lymphoma, 1 multiple myeloma and 1
      myelodysplastic syndromes received NAST from HLA-identical sibling donors.
      Peripheral blood stem cells were mobilized by G-CSF 300 microg/12 hours x 5 d.
      (2.15 -10.01) x 10(6) CD(34)(+) cells/kg were transplanted. A non-myeloablative
      conditioning regimen included fludarabine 30 mg.m(-2).d(-1) x 6 d;busulfan 4
      mg.kg(-1).d(-1) x 2 d or cyclophosphamide 50 mg.kg(-1).d(-1) x 2 d and
      antilymphocytic globulin 12 approximately 15 mg.kg(-1).d(-1) x 4 d. Cyclosporin A
      was used to prevent graft versus host disease (GVHD) alone and no G-CSF was
      administered after NAST. RESULT: Hematopoiesis reconstitution resumed on day 8 to
      day 19 (average of day 13). Severe mucositis was absent. Hepatic venoocclusive
      disease did not occur. Infectious complications were rare. Acute and chronic GVHD
      each occurred in 5 patients. Idiopathic pneumonia was developed in 5 patients. In
      the follow-up duration of 120 to 425 days, 16 of the 17 cases had a stable mixed
      or complete chimerical states. Fourteen of 17 patients are alive. CONCLUSION:
      NAST is an effective therapy in the treatment of hematological diseases with less
      complications, less blood transfusion and lower cost.

PMID- 14642178
TI  - [Comparison of conditioning regimens containing or no fludarabine in
      nonmyeloablative allogeneic peripheral blood stem cell transplantation].
AB  - OBJECTIVE: To investigate the therapeutic effect of conditioning regimen
      containing fludarabine in nonmyeloablative allogeneic peripheral blood stem cells
      transplantation (NAST) in the treatment of hematological diseases. METHODS:
      Thirty-six patients with acute leukaemia, severe aplastic anaemia, MDS and
      myelofibrosis received NAST from HLA matched donors' G-CSF mobilized peripheral
      blood stem cells after nonmyeloabalative conditioning. The conditioning regimen
      consisted of CTX, Ara-C, CsA, anti-CD(3) antibody or anti-thymocyte globulin and
      with or without fludarabine. GVHD prophylaxis was performed with cyclosporine
      combined methotrexate (no MMF group, n = 5) or mycophenolate mofetil (MMF group,
      n = 31). RESULTS: All of the treatment was generally well tolerated and all cases
      achieved engrafted of the donor cells. In fludarabine group, engraftment was
      observed in 87.5% (14/16) patients with complete donor chimerism, graft failure
      was 12.5% (2/16) and in no fludarabine group, 80% (16/20) and 20% (4/20),
      respectively. The incidence of acute GVHD (grade I - IV) was 27.8% (10/36) and
      chronic GVHD 22.2% (8/36). In fludarabine group, grade I - II aGVHD was 37.5%, in
      no fludarabine group, 20%. cGVHD was 12.5% in fludarabine group and in no
      fludarabine group 30%, respectively. Interstitial pneumonia (IP) was observed in
      16.7% (6/36) of the patients, being 18.7% (3/16) and 15% (3/20) in fludarabine
      and no fludarabine group, respectively. Overall survival rate was 80.5% (29/36)
      with a median follow-up of 13 months. CONCLUSIONS: There was no significant
      difference between fludarabine based (n = 16) and non-fludarabine based
      conditioning regimen (n = 20) in NAST for the treatment of hematological
      diseases, regarding for incidence of GVHD, IP, engraftment and survival.

PMID- 14642179
TI  - [Clinical study of a new protocol for acute graft-versus host disease prophylaxis
      in HLA-haploidentical bone marrow transplantation (BMT)].
AB  - OBJECTIVE: To explore the feasibility of a new protocol for acute graft versus
      host disease (aGVHD) prophylaxis in haploidentical bone marrow transplantation.
      METHODS: Thirty-eight high-risk leukemia patients underwent haploidentical G-CSF
      primed bone marrow transplantation without ex-vivo T cell depletion, the donors
      were given G-CSF 250 microg/d for 7 days prior to marrow harvest. All patients
      received a same chemo-radiation conditioning regimen, including cytarabin,
      cyclophosphamide and total body irradiation (TBI). GVHD prophylaxis regimen
      consisted of ATG, CsA, MTX, Mycophenolate mofetil (MMF) and anti-CD(25)
      monoclonal antibody (MoAb). RESULTS: All patients achieved engraftment of a
      median of 19 and 22 days for neutrophil and platelet, respectively. Cytogenetic
      analysis showed 100% donor hematopoietic cells in all recipients after
      transplantation. One of the twenty patients (5%) experienced grades II - IV acute
      GVHD. The recovery of CD(3)(+)CD(8)(+) T cells, CD(19)(+) cells and CD(56)(+)
      cells after transplantation was within 3 approximately 12 months. Of the 20
      patients, 16 were alive with minimal and limited chronic GVHD and karnofsky score
      over 90% in a median follow-up of 9 months. Disease free survival (DFS) rates was
      (80 +/- 9)%. CONCLUSION: G-CSF priming marrow graft along with sequential
      immunosuppressants, especially the addition of anti-CD(25) MoAb for aGVHD
      prophylaxis could achieve excellent engraftment, proper immune reconstitution and
      very low incidence of grade II - IV GVHD. The new protocol is effective and
      feasible in preventing severe acute GVHD and improving DFS.

PMID- 14642180
TI  - [Study on the in vivo effect of rhG-CSF on peripheral T lymphocyte].
AB  - OBJECTIVE: To investigate the mechanisms of in vivo rhG-CSF affecting T
      lymphocyte. METHODS: Peripheral blood and apheresis graft were obtained from
      sibling donors before and after G-CSF administration. Proliferation of peripheral
      blood mononuclear cells (MNC) stimulated by PHA before and after removing
      monocyte by plastic-adherence was detected by MTT test. Absolute number of MNC,
      costimulating molecules expression on antigen presenting cells (monocyte and B
      lymphocyte) and the number of CD(14)(+) cells before and after plastic-adherence
      treatment were analyzed by flow cytometry. RESULTS: After rhG-CSF administration,
      absolute peripheral blood monocyte counts increased by 4.2 +/- 1.74 times. By
      removing monocytes, proliferation of T cells after rhG-CSF administration partly
      restored, but remained 20.58% lower than that before G-CSF treatment. CD(86) co
      stimulating factor expression on monocyte declined (66.96 +/- 13.87)% and mean
      fluorescence intensity (MIF) decreased (31.31 +/- 12.91)% after rhG-CSF
      administration. Expression of CD(80) on B lymphocyte decreased (45.77 +/-
      26.58)%. CONCLUSIONS: The increased number of monocytes after rhG-CSF
      administration suppressed T-cell proliferation, which was partly the mechanism of
      the T-cell hyporesponsiveness. The fact that monocyte and B lymphocyte expressed
      low level of B(7) co-stimulating factor suggested that antigen present cells
      might also mediate the alteration of T-cell proliferation.

PMID- 14642181
TI  - [Identification of differentially expressed genes in Lin-CD34- and Lin-CD34+
      cells].
AB  - OBJECTIVE: To identify genes that differentially expressed in Lin(-)CD(34)(-) and
      Lin(-)CD(34)(+) cells. METHODS: With Lin(-)CD(34)(-) cells as tester and Lin(
      )CD(34)(+) cells as driver, cDNA subtractive library for Lin(-)CD(34)(-) cells
      was constructed using suppression subtractive hybridization technique. Part of
      clones in the library were sequenced and the homologue analysis was conducted
      against the DNA database in GenBank. RESULTS: 593 clones containing an average of
      300 - 500 bp insert were identified. Of them, 53 randomly selected ESTs were
      sequenced. Homologue analysis revealed that 37 ESTs represented 10 known genes,
      and the other 16 ESTs represented 4 novel sequences. CONCLUSION: Part of
      specifically expressed genes in Lin(-)CD(34)(-) cells were identified, which
      maybe related to Lin(-)CD(34)(-) cells' specific characteristics.

PMID- 14642182
TI  - [Inhibition of tumor angiogenesis in nude mice by adenovirus-mediated PF4 p17-70
      cDNA transfection].
AB  - OBJECTIVE: To investigate the in vivo effect of modified platelet factor 4 (PF4)
      p17-70 cDNA on tumor angiogenesis in nude mice. METHODS: The p17-70 cDNA was
      cloned into the AdEasy system to transfect packing cell line 293 and produce
      viral particles encoding p17-70cDNA (Ad p17-70). The integration of p17-70 cDNA
      was confirmed by RT-PCR and the P17-40 peptide Western blot. The biological
      activity of purified recombinant adenovirus was determined by umbilical veinal
      endothelial cell proliferation assay in vitro and in vivo tumor angiogenesis
      suppression of nude mice bearing human head and neck carcinoma. RESULTS: p17-70
      significantly inhibited in vitro proliferation of endothelial cells being 58%
      lower than that of empty vector and reduced tumor volume in vivo. The tumor mass
      was (0.086 +/- 0.054) g, (0.171 +/- 0.076) g and (0.195 +/- 0.067) g, the tumor
      volume was (16.7 +/- 5.2) mm(3), (36.5 +/- 23.7) mm(3) and (41.5 +/- 12.2) mm(3)
      in p17-70 cDNA transfected group, empty vector group and PBS group, respectively.
      Immunohistochemical staining demonstrated a decreased number of blood vessels in
      the tumors. CONCLUSION: P17-70 peptide mediated by adenoviral vector could
      inhibit the endothelial proliferation in vitro and the tumor growth in vivo.

PMID- 14642184
TI  - Anxiety on the Watchtower: The Hospital Epidemiologist and Emerging Infectious
      Diseases.

PMID- 14642183
TI  - [Low dose methotrexate combined with GM-CSF induced differentiation of U937
      cells].
AB  - OBJECTIVE: To explore the effect of methotrexate on acute monoblastic leukemia
      cells, and the potential role of low-dose methotrexate in the treatment of
      monoblastic leukemia. METHODS: By using U937 cell line as a model, the induced
      differentiation of MTX or GM-CSF or their combination was detected by NBT
      reduction test, morphological observation and CD(14) expression. TRAP-ELISA was
      used for measuring telomerase activity. RESULTS: After incubation with 20 nmol/L
      methotrexate for 24, 48, 72 and 96 hours, the size of the U937 cells increased,
      the nuclear/plasma ratio gradually decreased, NBT reductive test became positive,
      and CD(14) positive cells increased from 3% to 20% after 72 hours incubation,
      indicating partial differentiation. Treatment of U937 cells with 100 U/ml GM-CSF
      alone failed to induce differentiation. However, GM-CSF combined with low-dose
      methotrexate resulted in 63% of differentiated cells after 72 hours incubation,
      and telomerase activity of the U937 cells decreased from 2.11 (before treatment)
      to 1.48, 0.77, 0.24 (after treatment for 24, 48, 72 hrs respectively). The extent
      of the decrease of telomerase activity was in proportion with the degree of
      differentiation. CONCLUSION: Monoblastic leukemia might be treated with low-dose
      methotrexate plus GM-CSF as a differentiation induction regimen.

PMID- 14642185
TI  - Community-acquired Methicillin-resistant Staphylococcus aureus: Epidemiology and
      Potential Virulence Factors.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been isolated from
      patients in the community. Some of these strains may have origins in the
      hospital, but others appear to be novel and unrelated to known hospital strains.
      Community MRSA strains have several distinguishing characteristics that may
      enable them to more readily colonize and infect otherwise healthy individuals.
      This article reviews recent publications addressing the epidemiology of MRSA in
      the community, risk factors associated with carriage, potentially associated
      virulence factors, and concepts of strain fitness as they pertain to MRSA. MRSA
      likely will be an increasingly important pathogen in the community.

PMID- 14642186
TI  - Epidemiology and Prevention of Infections Related to Endoscopy.
AB  - Contaminated endoscopes are the most common cause of device-related nosocomial
      outbreaks in the United States. Because almost all outbreaks are related to
      breaches in reprocessing techniques, it is crucial that endoscope cleaning and
      disinfection are performed carefully. Key elements that should be emphasized are
      availability of and adherence to guidelines, thorough staff training, and
      ensuring proper equipment is used in the reprocessing. Encouraging endoscopists
      to notify infection control when they see unexpected postprocedure complications
      and document which endoscopes are used in each case are key elements in limiting
      the impact of outbreaks.

PMID- 14642187
TI  - Nosocomial Transmission of SARS.
AB  - Severe acute respiratory syndrome is a newly emerged infectious disease with
      moderately high transmissibility. Nosocomial outbreaks were responsible for the
      propagation of the epidemic worldwide. Health care workers (HCW) are at
      particular high risk because of their close contact with patients, involvement in
      medical procedures, and handling of excreta/fomites. Good hospital organization
      and appropriate infection control strategies are essential to prevent/interrupt
      disease transmission from patients to HCWs (and vice versa) and among inpatients
      and HCWs themselves. Education and training should target broadly to all HCWs.

PMID- 14642188
TI  - Estrogen Replacement Therapy to Prevent Recurrent Urinary Tract Infection in
      Postmenopausal Women.

PMID- 14642189
TI  - Antibiotic-associated Vulvovaginal Candidiasis.
AB  - Vulvovaginal candidiasis (VVC) is one of the most common causes of vaginitis, and
      its incidence has increased markedly during the past three decades. The
      widespread overuse of antibiotics has been suggested as one of the major factors
      contributing to the increasing incidence of VVC. However, evidence supporting
      this association has been limited because few studies with rigorous scientific
      methodology have been conducted. Moreover, existing data regarding the risk for
      developing VVC after antibiotic use are conflicting. This review examines the
      available information in the literature regarding antibiotic-associated VVC, its
      incidence, and its potential mechanisms. Implications for clinical practice and
      research are also discussed.

PMID- 14642190
TI  - Immune Regulation and Its Role in the Pathogenesis of Candida Vaginitis.
AB  - The pathogenesis of vulvovaginal candidiasis, which is caused by Candida
      albicans, is poorly understood. Despite a strong protective role for cell
      mediated immunity (CMI) against other mucosal candidal infections, numerous
      studies in humans and most animal models have revealed little to no role for CMI
      or other forms of acquired immunity against vaginal candidal infections. Studies
      suggest that this may be because of immunoregulatory mechanisms that inhibit more
      profound adaptive immune responses rather than the simple lack of responsiveness.
      Such regulatory mechanisms significantly influence the pathogenesis of Candida
      vaginitis.

PMID- 14642191
TI  - Erosive Vulvovaginitis.
AB  - The presence of erosive changes in the vulva, vagina, or both areas constitutes a
      major diagnostic and therapeutic challenge for clinicians. Often, biopsy is
      required to obtain an accurate diagnosis. Despite the wide differential
      diagnosis, therapeutic options often are limited, although new treatment
      modalities have been recently introduced.

PMID- 14642192
TI  - Impact of Changing Patterns of Antimicrobial Resistance in Uropathogens: Emerging
      Treatment and Strategies.
AB  - Urinary tract infection (UTI) is common, especially in women, and the
      microbiology of UTI is predictable. Over the past decade, numerous reports have
      documented increasing resistance among uropathogens to first-line agents for the
      treatment of UTI, especially trimethoprim/sulfamethoxazole (TMP/SMX). It is
      recommended that TMP/SMX should not be administered as empiric therapy for UTI in
      communities where resistance rates exceed 20%. However, reliable data regarding
      the true prevalence of resistance in a community are often lacking. Preliminary
      work has suggested that recent antimicrobial use is an important risk factor for
      infection with a TMP/SMX-resistant isolate. A better understanding of the
      epidemiology of resistance is needed to aid therapeutic decisions and devise
      interventions to reduce or slow emerging resistance.

PMID- 14642193
TI  - Molecular Epidemiology of Acute, Uncomplicated Urinary Tract Infections in Young
      Women.
AB  - Molecular biological methods, a relatively new addition to the epidemiologist's
      tool chest, are now applied to the study of urinary tract infection (UTI). By
      combining sound epidemiologic methods and the ability to genetically stratify UTI
      causing Escherichia coli, recent studies have added to our understanding of UTI.
      These advancements include the possible identification of outbreaks of community
      acquired UTI, the contribution of person-to-person transmission of E. coli to the
      risk for UTI in young women, and changes in the community prevalence and
      distribution of UTI caused by drug-resistant organisms. The application of
      molecular methods to future UTI research studies may yield novel approaches to
      UTI prevention.

PMID- 14642194
TI  - Cardiovascular Complications in Patients with HIV Infection.
AB  - As advances in early diagnosis and aggressive therapy, as well as better
      supportive care, become available to a larger number of patients with HIV
      infection, survival is being prolonged, and more patients are experiencing
      cardiac abnormalities. The most common cardiac manifestations of HIV disease are
      dilated cardiomyopathy, myocarditis, pericardial effusion, endocarditis,
      pulmonary hypertension, HIV-associated malignant neoplasms, and drug-related
      cardiotoxicity. The introduction of highly active antiretroviral therapy (HAART)
      regimens has substantially modified the course of HIV disease by lengthening
      survival and improving quality of life of HIV-infected patients. However, early
      data have raised concerns about HAART being associated with an increase in
      peripheral and coronary arterial disease. This review discusses the principal HIV
      associated cardiovascular manifestations and emphasizes new knowledge about their
      prevalence, pathogenesis, and treatment.

PMID- 14642195
TI  - Management of Antiretroviral Therapy in Neonates, Children, and Adolescents.
AB  - There have been tremendous advances in the prevention of mother-to-child
      transmission of HIV and treatment of HIV-infected children and adolescents.
      Although multiple classes of anti-HIV drugs are available that can control viral
      replication and stabilize immune function when used in combination, patients and
      their providers also must manage complex and frequently toxic regimens. This
      article summarizes official National Institutes of Health guidelines for the
      prevention of perinatal HIV infection and the management of pediatric and
      adolescent HIV infection, and provides the most current updates on indications
      for therapy, recommended first-line therapy, criteria for changing therapy,
      salvage therapy, and novel management strategies.

PMID- 14642196
TI  - Expatriate clinics and medical evacuation companies are a growth industry
      worldwide.
AB  - Globalization and the growth of tourism, which now includes "adventure" visits to
      very remote regions, has created new employment but also new problems. For
      example, elderly tourists break their hips where there is no competent orthopedic
      surgeon, a traveler gets bitten by a cobra in rural Cambodia where there is not
      even an "Ambu" bag to keep him oxygenated, and a tour guide develops high
      altitude cerebral edema on a remote Nepalese mountain. What would we do without
      organizations that are capable of removing such victims rapidly and safely to a
      place able to provide appropriate medical care? Fortunately, several well-staffed
      and well-equipped air ambulance companies stand ready almost worldwide to help 24
      hours a day. Medical assistance firms, which sell their own travel insurance
      and/or act as agents of large insurance companies, are also at hand and have
      offices in major cities worldwide. They have 24-hour telephone numbers and are
      prepared to advise a sick or injured traveler where he or she should go to obtain
      competent medical care. Most of these firms have regional medical advisors in
      strategic locations who maintain a network of contacts. They can ensure that an
      ill traveler is receiving appropriate care and will act as quality controllers.
      They are also able to advise whether medical evacuation to a higher level of care
      is needed and where the traveler should be evacuated to.

PMID- 14642197
TI  - Antimosquito precautions and medical chemoprophylaxis in French children with
      malaria.
AB  - BACKGROUND: France is the European country with the highest number of imported
      malaria cases (7,500 in 2000). The aim of this prospective study was to evaluate
      the nature and efficacy of prophylactic measures in children under 15 years of
      age referred for malaria. METHODS: Post travel questionnaires were given to the
      parents of malarial children in the emergency room. The study took place in two
      university hospitals in Marseilles, southern France, from August to October 2001.
      RESULTS: Eighty-eight children under 15 years of age were included in this 3
      month period. Most of them had been infected in Comoro archipelago. Almost two
      thirds used bed nets, but only 47% did so every night. Sprayed bed nets were used
      by 23%. Average compliances with cutaneous repellents, bedroom repellents and
      long-sleeved clothing were 32%, 24% and 26%, respectively. Air conditioners were
      uncommon. Only 22% of the children used chemoprophylaxis correctly, according to
      French recommendations. Five percent did not use any chemoprophylaxis, and 61%
      reported non recommended drug use. Although all the children traveled to
      chloroquine-resistant areas, chemoprophylaxis with mefloquine was less common
      than that with chloroquine + proguanil. No child fully complied with French
      recommendations concerning both anti mosquito measures and chemoprophylaxis.
      CONCLUSIONS: Insufficient use of antimalaria precautions by traveling families is
      associated with the high incidence of pediatric imported malaria in southern
      France. Travelers' education should be increased to allow the optimization of
      malaria prophylaxis.

PMID- 14642198
TI  - Imported malaria in Kuwait (1985-2000).
AB  - BACKGROUND: The objective of this study was to document the status of malaria
      infection and effect of preventive measures on the epidemiologic profile of
      imported malaria cases in Kuwait during 1985-2000. METHODS: The study included
      screening of two groups of individuals for malaria infection by microscopy; (1)
      all migrant workers from malaria-endemic countries on their first entry to
      Kuwait; and (2) all suspected malaria cases already residing in the country. The
      study period was divided into pre-war (1985-1990), postwar (1992-1997) and
      proactive preventive (1998-2000) periods. During the proactive preventive period,
      the home countries were also involved in screening for malaria infection in all
      prospective immigrants to Kuwait. RESULTS: The annual incidence of malaria cases
      detected during the pre-war, postwar and proactive preventive periods ranged
      between 465 and 1,229, 654 and 1,379, and 248 and 393, respectively. Plasmodium
      vivax infection was detected in 71% of the cases and P. falciparum in 27%. The
      number of malaria cases detected increased to >1,300 after the war during 1992
      1993. However, the number of malaria cases dropped significantly to less than 400
      during 1998-2000 (p80%) of malaria patients were young male adults between 21 and
      40 years of age. The data on drug resistance were not well defined, due to
      limited testing. CONCLUSION: This study suggests that the proactive preventive
      program to screen all prospective immigrants for malaria infection in their home
      countries significantly reduced the numbers of imported infections to <400
      cases/year, a drop of 52.6%. In addition, it also identified a group of settled
      immigrants, the majority of whom were at high risk for acquisition of malaria
      infection during their visit to home countries. There is an urgent need to target
      this group for prevention strategies such as education/information and other
      preventive measures against malaria infection.

PMID- 14642199
TI  - Travel in pregnancy: pregnant women's experiences and knowledge of health issues.
AB  - BACKGROUND: Long-distance travel is becoming increasingly common, and there are
      few evidence-based recommendations for pregnant women in this area. We aimed to
      investigate our patients in the third trimester to establish how common foreign
      travel was, how much knowledge they had, and where they had obtained information.
      METHODS: We performed a questionnaire survey of our patients in the third
      trimester in 2001 at the time of a routine ultrasound scan. All women booked to
      deliver in our unit were included. RESULTS: We received 138 out of a possible 151
      replies, and over half had traveled abroad in this pregnancy. Over a third of the
      trips were outside Europe. Over a third of the women traveled without sufficient
      insurance. Only a third sought advice prior to travel, and the commonest people
      consulted were their general practitioner and midwife. In general, knowledge on
      the subject was good, and was better among those who traveled. However, a third
      of the total group, and a quarter of those who traveled, did not know that air
      travel increased the risk of venous thromboembolism. CONCLUSIONS: Long-distance
      travel is common in pregnancy, and women are not always adequately prepared in
      terms of insurance and travel advice. More studies are required to provide
      evidence-based guidelines for this increasingly large proportion of women.

PMID- 14642200
TI  - Formation of edema and fluid shifts during a long-haul flight.
AB  - BACKGROUND: More than 1.5 billion passengers travel by aircraft every year. Leg
      edema, as a sign of venous stasis, is a well-known problem among passengers
      during and after long-haul flights. Until now, no studies have been done on the
      development of leg edema and fluid shifts under real flight conditions. The aim
      of our study was to evaluate edema formation in the leg and to investigate
      possible fluid shifts to the interstitial space under real flight conditions.
      METHODS: Twenty participants, 10 without risk and 10 with moderate risk for
      venous thrombosis, were selected. They flew from Vienna to Washington, flight
      time 9 h, and returned 2 days later. Investigations were done 48 h before the
      flight, between the fifth and eighth flight hour on board to Washington and back
      to Vienna, immediately after arrival in Vienna, and 1 and 3 days after arrival.
      Plethysmographic measurements were carried out using an optoelectronic scanner
      system (Perometer). Thickness of the skin was measured at the forehead and in
      front of the tibia. RESULTS: There were no differences in all measurements
      between both groups. The volume of the leg increased from 8242 +/- 1420 mL to
      8496 +/- 1474 mL after the flight (p <.001). Volume accumulation was distributed
      to the lower leg as well as to the thigh. Skin thickness in front of the tibia
      increased significantly during the flight (p <.05), and remained elevated 1 day
      after arrival. CONCLUSION: We have demonstrated that long-haul flights induce
      significant fluid accumulation in the lower extremity, involving the lower leg
      and thigh. This increase in tissue thickness was maintained for some days after
      the flights.

PMID- 14642201
TI  - Travel health advice for backpackers.
AB  - There has been an increasing trend for people to travel internationally, further
      afield, but fewer people are now going on programmed package tours. One of these
      groups of travelers comprises backpackers, who are distinct from endurance hikers
      or trekkers and longer-term and more remote expeditioners. Backpackers comprise
      individuals who travel alone or in a small group on a limited budget, and usually
      stay in hostels (hostelers), campsites, or similar low-cost accommodation, and
      carry their belongings in personal load-carrying equipment, most notably
      backpacks. Individual travel through backpacking, especially hosteling, appears
      to have become more popular for three probable reasons: travelers are seeking
      more cost-effective means of traveling and accommodation; they are looking to
      travel to regions where there is less likelihood of meeting fellow travelers; and
      they are looking for travel with more risk attached.

PMID- 14642202
TI  - Evaluation of malaria chemoprophylaxis in Bahrain.
AB  - The Kingdom of Bahrain is an archipelago located in the Arabian Gulf with a
      population of 650,000. A well-established network of 21 primary health care
      centers provide free health care for all residents, including citizens and
      expatriates. Patients requiring special investigation, consultation with
      specialists or admission are referred to the Salmaniya Medical Complex (SMC),
      which provides secondary and tertiary care. Malaria is a medical condition
      referred to SMC for medical care. Advice on appropriate prophylactic antimalarial
      regimens is a service provided by and limited to a public health advisory body,
      including the Public Health Directorate in the Ministry of Health, and a mini
      clinic known as a vaccination clinic located at one of the 21 primary health
      centers spread across the country. This clinic is staffed by a trained nurse; it
      provides services such as vaccination and malaria chemoprophylaxis advice. The
      recommended prophylactic drugs have to be purchased by the travelers from private
      pharmacies; they are considered to be over-the-counter (OTC) medications.

PMID- 14642203
TI  - The health of host communities: missing from printed travel health advice.
AB  - Travelers are becoming increasingly used to the need to seek appropriate health
      advice before embarking on trips, particularly to developing countries. Travel
      health advice is given in various ways and through various media.1 Printed
      material often accompanies a travel health professional's oral explanations.
      Leaflets, booklets, brochures and other printed material have been used for a
      long time. Some are customized by the travel health provider, some are produced
      by commercial bodies such as the pharmaceutical industry or travel goods
      producers, and some are given out by health authorities. All are either
      distributed by the health professional or are accessible to travelers for
      collection in clinics, in surgeries, in pharmacies or on the web.

PMID- 14642204
TI  - Plasmodium vivax malaria in spite of atovaquone/proguanil (malarone) prophylaxis.
AB  - A 70-year-old male scientist, who had returned 5 weeks earlier from Ethiopia, was
      admitted to the hospital with symptoms consistent with malaria. On physical
      examination, he had orthostatic hypotension. He was dehydrated and showed a mild
      clinical delirium. Abdominal examination revealed a possible spleen tip, and he
      had petechial lesions bilaterally below his knees. Laboratory data revealed his
      white blood cell count to be 4,500/mL, with 67% polymorphonuclear cells and 15%
      band forms. The hemoglobin level was 13.9 g/dL, and the platelet count was low,
      at 32,000/mL.

PMID- 14642205
TI  - The use of a rapid diagnostic test to determine malaria as a cause of death.
AB  - In a world of growing international travel, deaths due to imported infections,
      such as malaria, occasionally occur and can present diagnostic dilemmas. This
      report describes the novel use of a diagnostic test for a tropical disease in the
      postmortem examination of the cause of death.

PMID- 14642206
TI  - Cutaneous and medullar gnathostomiasis in travelers to Mexico and Thailand.
AB  - Gnathostomiasis is a rare nematode disease acquired by travelers to endemic
      areas. The most common clinical presentations are cutaneous forms; however,
      neurologic involvement can also occur. We present two cases of gnathostomiasis,
      one of them with severe neurologic complications, in Spanish travelers to
      Thailand and Mexico, who consumed local food and became infected.

PMID- 14642207
TI  - Pretravel health advice for asplenic individuals.

PMID- 14642213
TI  - Personal and family food choice schemas of rural women in upstate New York.
AB  - OBJECTIVE: The purpose of this study was to gain conceptual understanding of the
      cognitive processes involved in food choice among low- to moderate-income rural
      women. DESIGN: This interpretivist study used grounded theory methods and a
      theory-guided approach. PARTICIPANTS/SETTING: Sixteen women aged 18 to 50 years
      from varied household compositions were purposefully recruited in an upstate New
      York rural county. METHODS: Semi-structured interviews were conducted. Verbatim
      transcripts were analyzed using the constant comparative method. RESULTS: Study
      participants held both personal and family food choice schemas characterized by
      food meanings and behavioral scripts. Food meanings encompassed self-reported
      beliefs and feelings associated with food. Food choice scripts described
      behavioral plans for regularized food and eating situations. Five personal food
      choice schemas (dieter, health fanatic, picky eater, nonrestrictive eater,
      inconsistent eater) and 4 family food choice schemas (peacekeeper, healthy
      provider, struggler, partnership) emerged. CONCLUSIONS AND IMPLICATIONS: The
      findings advance conceptual understanding of the cognitive processes involved in
      food choice by demonstrating the existence of different food choice schemas for
      personal and family food choice situations. Further study is needed on food
      choice schemas in different populations in various food and eating situations.

PMID- 14642214
TI  - Applying the theory of planned behavior to predict dairy product consumption by
      older adults.
AB  - OBJECTIVE: The purpose of this study was to explain intention to consume dairy
      products and consumption of dairy products by older adults using the Theory of
      Planned Behavior (TPB). The factors examined were attitudes, subjective norms,
      and perceived behavioral control. DESIGN: A cross-sectional questionnaire was
      administered. SETTING: Community centers with congregate dining programs, group
      classes, and recreational events for older adults. SUBJECTS: One hundred and
      sixty-two older adults (mean age 75 years) completed the questionnaire. Subjects
      were mostly women (76%) and white (65%), with about half having less than a high
      school education or completing high school. VARIABLES MEASURED: Variables based
      on the TPB were assessed through questionnaire items that were constructed to
      form scales measuring attitudes, subjective norms, perceived behavioral control,
      and intention to consume dairy products. Dairy product consumption was measured
      using a food frequency questionnaire. ANALYSIS: Regression analyses were used to
      determine the association between the scales for the 3 variables proposed in the
      TPB and intention to consume and consumption of dairy products; the alpha level
      was set at.05 to determine the statistical significance of results. RESULTS:
      Attitudes toward eating dairy products and perceived behavioral control
      contributed to the model for predicting intention, whereas subjective norms did
      not. Attitudes toward eating dairy products were slightly more important than
      perceived behavioral control in predicting intention. In turn, intention was
      strongly related to dairy product consumption, and perceived behavioral control
      was independently associated with dairy product consumption. CONCLUSIONS AND
      IMPLICATIONS: These results suggest the utility of the TPB in explaining dairy
      product consumption for older adults. Nutrition education should focus on
      improving attitudes and removing barriers to consumption of dairy products for
      older adults.

PMID- 14642215
TI  - Development and validation of a self-efficacy measure for fat intake behaviors of
      low-income women.
AB  - OBJECTIVE: To develop a valid self-efficacy measure for eating low-fat diets in
      low-income women. DESIGN: Cognitive interviews followed by self-administered
      questionnaires. PARTICIPANTS/SETTINGS: 206 (6 + 200) nonpregnant black and white
      women participating in Head Start and the Special Supplemental Nutrition Program
      for Women, Infants and Children (WIC) in Wisconsin. VARIABLES MEASURES: A 13-item
      self-efficacy measure for eating low-fat diets. ANALYSIS: Content analysis and
      factor analyses. RESULTS: After cognitive interviews, 3 items were removed from a
      draft instrument. Factor analyses were carried out using data from 200
      questionnaires that were randomly selected from a pool of 487 respondents: 100
      for exploratory factor analysis (EFA) and 100 for confirmatory factor analysis
      (CFA). Based on EFA, the 10-item pool was further reduced to 8 items, and 3
      domains emerged: negative affect, positive affect, and availability. The results
      of CFA showed excellent model fit to the data (chi 2/df = 1.2, non-normed fit
      index = 1.0, comparative fit index = 1.0, incremental fit index = 1.0, root mean
      square error of approximate =.046). This measure demonstrated excellent
      reliabilities (Cronbach alpha : .82-.92; composite reliability: .92-.99) and
      construct and convergent validities. CONCLUSIONS AND IMPLICATIONS: Information
      obtained from this revised instrument can be used among low-income women to
      measure self-efficacy for eating low-fat diets. This is an important step in
      developing more targeted and thus more effective education messages to help low
      income women modify their fat intake behaviors.

PMID- 14642216
TI  - Development and testing of a nutrition-teaching self-efficacy scale for
      elementary school teachers.
AB  - OBJECTIVE: To develop and validate the Nutrition-Teaching Self-Efficacy Scale
      (NTSES) and investigate the time spent teaching nutrition and the nutrition
      teaching self-efficacy of Maryland elementary school teachers. DESIGN: A
      questionnaire collected information on teacher demographics. The NTSES was
      adapted from science- and health-teaching self-efficacy scales, reviewed by
      experts, and pretested with elementary teachers. Both were converted to an on
      line format for distribution statewide. Eighty elementary school teachers
      participated. ANALYSIS: Cronbach alpha and factor analysis established internal
      consistency and were used to refine the NTSES. Analysis of variance and
      independent sample t tests were used to compare mean scores on the NTSES and
      subscales to time spent teaching nutrition. RESULTS: The NTSES was determined to
      be a valid measure of nutrition-teaching self-efficacy. Higher nutrition-teaching
      self-efficacy scores were associated with spending more time teaching nutrition
      (P <.03). CONCLUSIONS AND IMPLICATIONS: The NTSES is a useful tool for
      determining nutrition-teaching self-efficacy in this population and is
      recommended as part of nutrition education needs assessments among teachers.
      Higher nutrition-teaching self-efficacy may result in more time spent teaching
      nutrition.

PMID- 14642217
TI  - Using a theory-driven approach to design a professional development workshop.
AB  - The objective of this study was to show how a theory- driven approach to program
      planning was used to design and evaluate a professional development workshop. Our
      method was to demonstrate modeling of theory use as a teaching strategy. The
      Theory of Planned Behavior was used to structure all components of a 6-hour
      workshop. This workshop significantly increased participants' intention to use
      theory in designing programs (P <.0001). Educators can apply the methods
      demonstrated here to systematically use theory in the development,
      implementation, and evaluation of their workshops, staff training, and curricular
      materials for professionals and consumers.

PMID- 14642218
TI  - Application of modern biotechnology to food and agriculture: food systems
      perspective.
AB  - The purpose of this article is to provide nutrition educators with an
      introduction to a range of considerations and forces that are driving the
      application of modern biotechnology in the food and fiber sector based on a food
      systems perspective. In doing so, the following issues are critically assessed:
      (1) the global debate on how to regulate genetically engineered (GE) foods and
      crops, (2) cultural differences in public perceptions of GE foods, and (3)
      evaluation of selected GE traits against the principles of social, economic, and
      ecological sustainability, including the potential of modern agricultural
      biotechnology to enhance global food security. Where appropriate, we also review
      other agricultural technologies and the broader political, social, and economic
      contexts in which these technologies have been introduced. Finally, we offer
      recommendations for how multiple stakeholder groups, including policy makers,
      biotechnology advocates, and nutrition educators, can move toward a more informed
      dialogue and debate on this issue.

PMID- 14642219
TI  - The Nutritional SCATTERGORIES game: adding zest to a nutrition course.

PMID- 14642220
TI  - Recipe development project using commodity food products.

PMID- 14642221
TI  - Making new foods fun for kids.

PMID- 14642223
TI  - [Transitional bladder carcinoma TaG1: role of the EGFr tyrosin kinase activation
      in the cellular proliferation].
AB  - BACKGROUND AND OBJECTIVE: The purpose of this work was to study if the expression
      of EGFr oncoprotein and the rate of tumoral cell proliferation in TaG1
      transitional bladder carcinoma were related and if this relationship influences
      the potential aggressivity of the neoplasia. PATIENTS AND METHOD: Twenty-eight
      patients with TaG1 (non-invasive papillary and well differentiated) transitional
      bladder carcinoma were randomly selected. EGFr was determined by a
      semiquantitative immunohistochemical method in three intensity levels. The
      proliferative tumoral cell activity was determined by the PCNA index, that is,
      the relation between the total number of tumor cells and the number of tumor
      cells with nuclear PCNA-immunoreactivity expressed in percentage. RESULTS: The
      rate of cellular tumour proliferation (PCNA index) was significantly higher in
      those tumors with EGFr's greater expression (p=0.005). The EGFr expression was
      associated with tumor recurrence (p=0.012). CONCLUSIONS: The major expression of
      EGFr oncoprotein in tumours with higher rate of cell proliferation indicates that
      it may be influenced by the activity of such oncoprotein. The binding of a ligand
      to the EGFr leads to intracellular tumor proliferation, hence possibly favouring
      a more aggressive biological behavior.

PMID- 14642224
TI  - [Generic drug prescription at discharge from a hospital emergency service].
AB  - BACKGROUND AND OBJECTIVE: Drug prescription at hospital discharge often implies
      continuation of the treatment in primary health care. The aim of this study was
      to assess prescription of generics at discharge from a hospital emergency
      service. MATERIAL AND METHOD: Longitudinal and retrospective study, on a random
      sample of medical reports in a hospital emergency service during one year (August
      2000 to July 2001). Information on the medical specialty, prescribed generic
      drugs and marked availability of the corresponding generic drugs pharmaceutical
      specialties was collected. Factors associated with generic prescription were
      analyzed by means of logistic regression analysis. RESULTS: A sample of 1,245
      medical reports was selected in which 2,315 drugs were prescribed. Although
      generic drugs were available for 33.3% (CI 95%, 31.4-35.2) of prescriptions, 9.5%
      (95% CI, 8.3-10.7) of prescribed drugs were generics. The average price of
      trademark prescribed medicines, for which there was a generic equivalent, was
      7.09 Euros (95% CI, 6.54-7.63 Euros), and that of the corresponding generic
      versions was 5.08 Euros (95% CI, 4.68-5.48 Euros). Variables associated with
      generic drug prescription included the particular study period (OR=1.35; 95% CI,
      0.99-1.84), the medical specialty of the prescriber (OR=1.40; 95% CI, 1.05-1.86),
      availability of generic drugs (OR=1.76; 95% CI, 1.30-2.39) and low price of
      prescribed drugs (OR=2.67; 95% CI, 1.80-3.98). CONCLUSION: In spite of the
      availability of generic drugs, prescription of generic drugs at discharge of this
      hospital emergency service was low. Prescription and use of generic drugs should
      be promoted in hospitals.

PMID- 14642225
TI  - [Appropriateness and complexity of the psychiatric emergencies in a general
      hospital].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to provide data about the
      characteristics of consultations in a Psychiatric Emergency Unit of a General
      Hospital. PATIENTS AND METHOD: We evaluated prospectively all patients attended
      in the Psychiatric Emergency Unit of the Hospital Clinic of Barcelona over a
      period of 40 days. A standardized registry was applied. RESULTS: The sample
      consisted of 1,054 cases (52.9% women and 47.1% men). The most frequent reason
      for consultation was anxiety (33.4%). Some medication was administered in 59.4%
      cases and 20.5% of patients were hospitalized. The consultation was considered
      appropriate in 60.1% cases. Complementary exams were performed in 28.9% patients.
      In 21.7% cases, the patient had to be studied by more than one specialist.
      CONCLUSIONS: Consultations to a Psychiatric Emergency Unit may be complex, and
      therefore it seems reasonable that a general hospital has to be the ideal
      location for these units.

PMID- 14642226
TI  - [Antioxidant and fat intake in patients with polinic asthma].
AB  - BACKGROUND AND OBJECTIVE: The aim of our work was to evaluate the dietary intake
      of patients with asthma. PATIENTS AND METHOD: A total of 54 subjects with asthma
      were enrolled (average age 23.59 +/- 9.6 years). In all patients, we determined
      weight, height and the body mass index and a three days nutritional questionnaire
      was administered. RESULTS: The total calories intake was normal. Distribution of
      calories was: 39.7% carbohydrates, 19.4% proteins and 40.9% lipids. Low intakes
      of vitamin A, D, E, thiamine and folic acid were detected, and an adequate intake
      of vitamin K, C, niacin and B12 was observed. The mineral intake showed an
      increase in calcium and a decrease in magnesium, zinc, iodine and selenium. The
      intake of polyunsaturated omega-9 fatty acids was 34.8(12.7) g/day, that of
      polyunsaturated omega-6 fatty acids was 5.7(3.1) g/day, and the intake of
      polyunsaturated omega-3 fatty acids was 0.85(0.31) g/day. Saturated fats
      represented a 18.4%. The omega6/omega3 ratio was 6.63. CONCLUSIONS: Asthmatic
      patients have a low intake of vitamins A and E but an increase in the intake of
      saturated fatty acids.

PMID- 14642227
TI  - [The new European regulation on herbal traditional drugs. Application to the
      Spanish regulation].

PMID- 14642228
TI  - [Hartveit labyrinth and pseudoangiomatosis stromal hyperplasia of the breast: a
      new route in mammary tumoral dissemination?].

PMID- 14642229
TI  - [Strongyloides stercoralis: risk factors for disseminated infection].

PMID- 14642230
TI  - [Benefits of physical activity and harms of inactivity].
AB  - Epidemiological research has consistently shown that physical activity decreases
      the risk of coronary heart disease, hypertension and stroke. The finding that a
      low level of physical activity is a major determinant of the growing epidemics of
      obesity is also firm and consistent. The direct association existing between a
      sedentary lifestyle and the incidence of diabetes mellitus is solid and of great
      importance for public health. Additional benefits from a a physically active
      lifestyle are a reduction in the incidence and prevalence of osteoporosis, lower
      risk of falls and fractures in the elderly, and a lower risk of anxiety and
      depression. Although evidence is less consistent, low levels of physical activity
      have been related to a higher risk of colon, breast and lung cancer. Some
      preliminary evidence relates physical activity with a lower risk of dementia.
      During the last three decades a huge amount of epidemiological research has led
      to uniform conclusions about the benefits of a physically active lifestyle. In
      spite of this fact, the prevalence of sedentary lifestyles is rising. Therefore,
      health promotion interventions are urgently needed to reach the objective of
      engaging in regular and moderate physical activity for at least 30 minutes per
      day in most, preferably all, days of the week.

PMID- 14642231
TI  - [Postpartum depression].

PMID- 14642232
TI  - [A secure job for ever].

PMID- 14642233
TI  - [Web pages citation and error 404].

PMID- 14642234
TI  - [Epidemic nephropathy in Spain: first imported case].

PMID- 14642235
TI  - [Folate usage to prevent neural tube defects among population attended in a
      reference hospital].

PMID- 14642236
TI  - [Ventriculoencephalitis due to coinfection of cytomegalovirus and HHV-6 diagnosed
      in a living AIDS patients].

PMID- 14642237
TI  - [Adult living donor liver transplantation. Analysis of the first 30 cases].
AB  - INTRODUCTION: In the last 2-3 years, adult living donor liver transplantation
      (ALDLT) has been developed on an international scale, multiplying the number of
      procedures performed. Despite this, analysis of the results is still incomplete.
      The aim of the present study was to perform a descriptive analysis of the results
      after the first 3 years of the initiation of the program. MATERIAL AND METHODS:
      During this period, 30 ALDLT were performed. In all procedures, right lobe grafts
      were used. The mean age of donors and recipients was 31.8 and 52.7 years,
      respectively. The main indication for liver transplantation was liver cirrhosis
      due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child
      Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma.
      RESULTS: Donors: The mean volume of the remnant liver was 632 cc (40.5% of the
      previous hepatic mass). Ten donors (33%) presented complications. The most
      frequent complication was biliary fistula (20%) and three patients required
      reintervention. The mean length of hospital stay among donors was 11.7 days.
      Recipients: The mean weight of the graft was 775 g, with a mean difference
      between graft weight and that of the recipient of 1.11. Fifteen recipients (50%)
      presented biliary leaks and nine of these (30%) required reintervention. There
      were no graft losses for technical reasons. Four patients died. With a median
      follow-up of 14 months, actuarial survival at 18 months was 92.9%. CONCLUSION:
      ALDLT is an effective method for reducing the number of patients on the waiting
      list. The probability of survival is similar to that of cadaveric
      transplantation. Biliary complications in the recipient constitute a problem, the
      long-term repercussions of which remain to be resolved.

PMID- 14642238
TI  - [Evaluation of a rapid test (ImmunoCard STAT! HpSA) for Helicobacter pylori
      detection in stools].
AB  - INTRODUCTION: The use of a rapid diagnostic technique may be extremely useful for
      the management of Helicobacter pylori infection. A new immunochromatographic in
      office test (ImmunoCard STAT! HpSA, Meridian Diagnosis Inc, Cincinnati, Ohio,
      USA) for the detection of H. pylori in feces has recently become available. The
      aim of the present study was to evaluate the diagnostic reliability and
      reproducibility of the ImmunoCard STAT! HpSA test in patients with dyspepsia.
      PATIENTS AND METHODS: Sixty-three dyspeptic patients were enrolled. H. pylori
      status was determined by CLO-test and Giemsa staining of antral biopsy. Patients
      with a positive result for both tests were considered infected and those with a
      negative result for both tests were considered not infected. Fecal H. pylori
      antigen was tested twice by ImmunoCard STAT! HpSA. The sensitivity, specificity,
      positive predictive value and negative predictive value of each determination
      were calculated. The concordance between the two determinations was evaluated
      using Kappa statistics. RESULTS: Of the 63 patients, 46 were infected by H.
      pylori. Sensitivity, specificity and positive and negative predictive values were
      89-91%, 86-93%, 96-98% and 72-75%, respectively. The correlation coefficient
      between determinations was 0.845. CONCLUSION: The new ImmunoCard STAT! HpSA test
      shows good sensitivity and reproducibility. Therefore, it could be highly useful
      in the management of H. pylori infection.

PMID- 14642239
TI  - [Diaphragmatic hernia of Morgagni-Larrey in adults: analysis of 10 cases].
AB  - Congenital diaphragmatic hernia of Morgagni-Larrey is a rare entity that usually
      presents on the right side. These hernias, occurring in the anterior midline
      through the sternocostal hiatus of the diaphragm, are usually discovered
      incidentally when the patient has reached adulthood, or when they become
      symptomatic due to intestinal involvement (occlusive symptoms) or when
      respiratory dysfunction occurs. We present 10 patients (mean age: 69 years) with
      symptomatic sternocostal hernia and intestinal occlusion. In 7 patients, the
      hernia was located on the right (Morgagni's hernia) and in three it was located
      on the left (Larrey's hernia). Most of the patients presented important
      associated comorbidity, mainly cardiovascular and neoplastic. Surgical treatment
      consisted of reduction of the contents of the herniated sac and hernia repair
      through simple suture with or without mesh for reinforcement, mainly through the
      abdominal approach. Mortality in this series was nil. The infrequency of this
      entity and its diagnosis mainly in adults, with a high prevalence of
      circumstances favoring abdominal hernias, suggest that an embryological defect of
      the sternocostal foramina of Morgagni or Larrey are an essential element in the
      physiopathology of these processes.

PMID- 14642240
TI  - [Purtscher's retinopathy: a rare complication of acute non-alcoholic
      pancreatitis].
AB  - Purtscher's retinopathy is a rare complication of acute alcoholic pancreatitis
      that is characterized by the development of cotton-wool exudates and retinal
      hemorrhages located around the optic disk. Its development is due to ischemic
      phenomena in the posterior pole of the retina due to microemboli in the retinal
      arterioles and capillaries. This complication is not related to a poorer
      prognosis of acute pancreatitis and the retinopathy usually has a favorable
      outcome with disappearance of the ophthalmic lesions and restoration of visual
      acuity after 4-6 weeks in most cases. However, some patients may show residual
      lesions, especially if optical atrophy occurs. We present a 40-year-old woman
      with loss of visual acuity due to Purtscher's retinopathy during the course of
      mild acute idiopathic pancreatitis.

PMID- 14642241
TI  - [Ulcerative colitis associated with idiopathic thrombocytopenic purpura].
AB  - Multiple hematological anomalies have been described in association with chronic
      inflammatory bowel disease. Idiopathic thrombocytopenic purpura is an autoimmune
      disease characterized by the presence of isolated thrombopenia with a normal or
      increased number of megakaryocytes in bone marrow and absence of splenomegaly.
      Several case reports of idiopathic thrombocytopenic purpura associated with
      chronic inflammatory bowel disease, mostly ulcerative colitis, have been
      published in the literature. The pathogenic mechanism through which these
      entities are associated is unknown. Several treatments have been used, varying
      from short courses of steroids to the use of immunosuppressive agents and
      splenectomy, depending on the severity of the symptoms. We describe the case of a
      woman with ulcerative colitis and idiopathic thrombocytopenic purpura, in which
      the latter first presented when the patient was undergoing treatment with
      corticosteroids and cyclosporin, one of the therapeutic options for controlling
      thrombopenic purpura. Platelet deficiency persisted despite treatment with
      azathioprine and colectomy, also described as a possible curative treatment.

PMID- 14642242
TI  - [Gastrointestinal bleeding after endoscopic treatment of polypoid hamartoma
      (adenoma of Brunner's glands)].
AB  - The incidence of polypoidal tumors in the duodenum is scarce and Brunner's gland
      tumors represent 11% of these proliferations. Brunner's gland polypoid hamartoma
      or adenoma is a highly infrequent benign polypoid proliferation of Brunner's
      glands that is usually asymptomatic, although gastrointestinal bleeding or
      intestinal obstruction may sometimes occur. We present the case of a woman with
      an incidental diagnosis of duodenal polypoid hamartoma. The lesion was resected
      with polypectomy loop and at 48 h, the patient presented gastrointestinal
      bleeding as a complication. We describe the endoscopic treatment of the lesion
      and this complication.

PMID- 14642243
TI  - [Role of the hepatitis B virus X protein (HBx) in immune response and tumoral
      progression].

PMID- 14642244
TI  - [Intraductal papillary mucinous tumor of the pancreas: a more unknown than
      infrequent entity].

PMID- 14642245
TI  - [Clinical guideline on the management of the patient with dyspepsia].

PMID- 14642246
TI  - [Gastroduodenal tuberculosis: a cause of pyloric stenosis].

PMID- 14642247
TI  - [Primary biliary cirrhosis and pregnancy: benefit of ursodeoxycholic acid
      therapy].

PMID- 14642248
TI  - [Clear cell hepatocarcinoma].

PMID- 14642249
TI  - [Advanced liver fibrosis secondary to methotrexate treatment].

PMID- 14642250
TI  - [Infectious diseases and inmigration].

PMID- 14642251
TI  - [Health in the immigrant population: prevalence of latent tuberculosis, hepatitis
      B, hepatitis C, human immunodeficiency virus and syphilis infection].
AB  - INTRODUCTION: To describe the prevalence of infectious diseases in immigrants.
      METHODS: The Mantoux tuberculin skin test and serology testing for hepatitis B,
      hepatitis C, HIV and syphilis were performed in 488 immigrants. RESULTS: A
      positive reaction to the Mantoux (> or = 10 mm) was found in 19.1% of individuals
      from Africa, 9.6% from Eastern Europe and 5.8% from South America (p < 0.001).
      With regard to hepatitis B, 2.5% of the Africans, 2.1% of the Eastern Europeans
      and none of the South Americans were carriers of the virus (p 5 0.02).
      CONCLUSIONS: The prevalence of infectious diseases in immigrants varies according
      to their country of origin.

PMID- 14642253
TI  - [Timing of bacterial colonization in severe burns: is strict isolation
      necessary?].
AB  - INTRODUCTION: Infection is still one of the main causes of mortality in severe
      burn patients. Strict isolation has been used for the prevention of infection,
      but the efficacy of this measure is debatable. The aim of this study was to
      determine the timing of bacterial colonization in these patients and to ascertain
      whether strict isolation is indicated. METHODS: Thirty consecutive children with
      severe burns were studied. Patients were only barrier-nursed during dressing
      changes. On admission and twice weekly over the entire hospital stay, burn,
      sputum, gastric aspirates, feces, and blood samples were obtained for culture.
      All isolates were tested for specific biotypes. Results were studied with linear
      regression and repeated measures ANOVA to determine the timing of colonization
      and cross-colonization between patients. RESULTS: On admission, normal cutaneous
      flora were isolated from burn cultures of all patients. The remaining cultures
      were negative. After one week, gastric aspirates were found to be colonized by
      gram-negative bacteria and fungi. This was followed by colonization of feces,
      burn, and sputum cultures. Biotype identification showed unidirectional
      colonization from the gastrointestinal tract to burns and upper airway. There
      were no cross infections between patients. CONCLUSIONS: Microbial colonization in
      severe burn patients was endogenous in nature and there were no cross infections.
      Thus, strict isolation is not necessary in burn centers, except during outbreaks
      of multi-resistant microorganisms.

PMID- 14642252
TI  - [Immunological, virological and clinical response in patients infected with HIV
      after highly active antiviral therapy with nelfinavir: prospective cohort study].
AB  - INTRODUCTION: To assess the long-term effectiveness, safety and response-related
      factors in a cohort of HIV-infected persons receiving antiretroviral therapy
      containing nelfinavir. Design and setting. Prospective, non-randomized
      multicenter study. METHOD: A total of 792 patients were included: 254 (32.1%)
      treatment-naive patients and 538 (67.9%) patients previously treated with
      protease inhibitors who were switched to a nelfinavir-containing regimen due to
      virological failure or intolerance. Factors related to virological response and
      to treatment failure were assessed by standard survival techniques and Cox
      proportional risk models. RESULTS: Nelfinavir was well tolerated; treatment had
      to be interrupted in only 57 patients (7.1%) because of toxicity. During a median
      follow-up of 12 months, 31 patients (3.9%) experienced a new AIDS-defining event
      or death, and 463 (58.4%) showed immunological response. Overall, 52% patients
      achieved plasma HIV-1 RNA levels below 500 copies/mL (57% of naive and 49% of
      previously treated patients), but a high rate of virological rebound (24% and
      49%, respectively) was observed. Low baseline viral load and few prior treatments
      were factors related to virological response. Naive treatment status and a high
      increase in CD4 cell count were predictive of longer viral response. CONCLUSIONS:
      Highly active antiretroviral therapy with a nelfinavir-containing regimen was
      associated with favorable virological response in nearly half of previously
      treated patients, and most experienced clinical and immunological benefits.
      Nevertheless, the limited duration of virological response indicates the need for
      new alternative drugs.

PMID- 14642254
TI  - [Meningococcal disease: clinicopathological correlation].
AB  - INTRODUCTION: Clinicopathological correlation studies of cases admitted as
      meningococcal disease are scarce, although they can serve to elucidate clinically
      obscure cases. METHODS: A descriptive approach was used to analyze 42 necropsies
      following clinical diagnosis of meningococcal disease, verifying the agreement
      between histopathological and clinical findings evaluated according to three
      clinical forms of meningococcal disease (MD) in children and adults: septicemic
      meningococcal disease (MD-S), meningococcal disease with meningitis and
      septicemia (MD-MS), and meningococcal disease with meningitis/meningoencephalitis
      alone (MD-M). RESULTS: Of the total, 81% met the confirmatory clinical criteria;
      56% were 14 years of age or less and 44% were over 14 years. The principal causes
      of death included multiple organ failure (59%) (associated with shock in 65% of
      cases); cerebral edema (29%); and myocarditis (12%). There was a high
      clinicopathological correlation between septic shock and diffuse adrenal
      hemorrhage (77%) and between respiratory failure and pulmonary alterations (77%),
      and a low correlation between heart failure and cardiac involvement (27%) and
      between diarrhea and enteritis (25%). Myocarditis and disseminated fibrin
      thrombi, especially in the skin, lungs, and kidneys, predominated in the MD-S and
      MD-MS forms, while diffuse adrenal hemorrhage and enteritis predominated in MD-S.
      The correlations between the clinical and pathological diagnoses of the MD forms
      were: MD-S, 17/11 (65%), MD-MS, 14/14 (100%), and MD-M, 3/2 (67%). CONCLUSION:
      There was significant correlation between clinical and pathological diagnoses (P
      <.0001) according to the various forms of MD. However, histopathological analysis
      did not differentiate between the MD-S and MD-MS forms, which merely represented
      variations in severity.

PMID- 14642255
TI  - [Seroprevalence of infection due to Echinococcus granulosus in the population of
      Castilla and Leon (Spain)].
AB  - INTRODUCTION: Human hydatidosis is a prevalent zoonotic disease in the Castilla y
      Leon region of Spain. The aim of this study is to investigate the seroprevalence
      of Echinococcus granulosus infection in this region. METHODS: We studied 4824
      serum samples from a random, representative population of healthy individuals
      from each province of Castilla y Leon, obtained over one year. An indirect enzyme
      immunoassay developed in our laboratory was used to determine the presence of IgG
      antibodies against Echinococcus granulosus in these samples. RESULTS: IgG
      antibodies against Echinococcus granulosus were detected in 3.4% (164/4824) of
      samples studied, with a range of 1.26% to 7.10%, depending on the province.
      Antibody seroprevalence increased significantly with age, but there was no
      significant sex-related difference (3.66% men vs. 3.14% women). CONCLUSION: The
      seroprevalence of Echinococcus granulosus infection in Castilla y Leon is still
      high. These data contribute to hydatidosis surveillance within the control
      program for this disease.

PMID- 14642256
TI  - [Vertebral osteomyelitis due to Candida spp].
AB  - INTRODUCTION: Vertebral osteomyelitis is rarely caused by Candida species;
      therefore, a high index of suspicion is required for its diagnosis. METHODS: We
      describe three cases of vertebral osteomyelitis due to Candida spp. diagnosed
      over a seventeen-year period. RESULTS: Among 110 episodes of vertebral
      osteomyelitis, three were caused by Candida spp. All three patients had risk
      factors for Candida infection: diabetes mellitus (2), immunosuppression (2),
      central venous catheters (3), antibiotic use (2) and parenteral nutrition (2).
      Radiographic studies and culture of vertebral specimens established the diagnosis
      in two patients. Blood cultures were positive in the third patient, who had
      aortic infectious endocarditis. Two of the three cases achieved clinical cure
      with medical treatment and the third relapsed after six months of therapy with
      fluconazole. CONCLUSION: Candidal vertebral osteomyelitis is an uncommon disease
      that should be suspected in patients with risk factors for candidemia.

PMID- 14642257
TI  - [Guidelines for the treatment of infection due to Aspergillus spp].
AB  - These guidelines, which are based on recommendations established by several drug
      agencies, analyze various aspects of the clinical management of invasive
      aspergillosis in immunosuppressed patients.

PMID- 14642258
TI  - [Antiparasite therapy].
AB  - The lack of any parasite vaccine makes prevention against parasitic diseases to
      be based, as in the past, in ecological measures such as the environmental health
      and vector control to interrupt the biological cycle; on the other hand, it is
      also based in anti-parasite drugs. Once the disease has been acquired it is just
      possible to take medication. Studies on the way of action allow to understand
      more about the physiology of the parasite and, on the other hand, to understand
      better the physiology of the parasite allows to design new more effective drugs.
      However, the vast majority of these new drugs have been obtained thanks to
      intelligent and selective screening of generic molecules more than from the
      result of the knowledge of the biochemistry of the parasite. Despite all this, it
      is well known the mechanisms of action of many antiparasite drugs which have led
      us, when possible, to the discussion about possible targets to give an idea of
      how the rational approximation to design new medicaments is done.

PMID- 14642259
TI  - [Thai woman with hematuria y eosinophilia].

PMID- 14642260
TI  - [Parotid tumor in a patient with AIDS].

PMID- 14642261
TI  - [Endocarditis due to Lactobacillus acidophilus in a patient with structural heart
      disease].

PMID- 14642262
TI  - [Enterocolitis due to methicillin-resistant Staphylococcus aureus].

PMID- 14642263
TI  - [First case of acute pericarditis due to catalase-negative Staphylococcus
      aureus].

PMID- 14642264
TI  - [Preliminary assessment of new antigen detection methods for prompt diagnosis of
      syncytial respiratory virus].

PMID- 14642265
TI  - [Isolation and identification of Plesiomonas shigelloides: three cases of
      diarrhea].

PMID- 14642266
TI  - Lost in space: misregulated positional cues create tripotent neural progenitors
      in cell culture.
AB  - In a widely held view of vertebrate CNS development, neurons, astrocytes, and
      oligodendrocytes arise from a common tripotent progenitor cell. However,
      tripotent progenitors have never been detected in developing embryos. In this
      issue of Neuron, Gabay et al. show that tripotent progenitors can be created in
      vitro by deregulation of normal dorsoventral positional cues.

PMID- 14642267
TI  - Less means more: inhibition of spontaneous firing triggers persistent increases
      in excitability.
AB  - Modulation of intrinsic excitability is an alternative to classical synaptic
      plasticity for implementing activity-dependent changes in neuronal networks. In
      this issue of Neuron, Nelson et al. reveal a new form of plasticity of intrinsic
      excitability that can be triggered rapidly when synaptic inhibition reduces
      spontaneous firing, resulting in persistent enhancement of firing rate and
      neuronal gain.

PMID- 14642268
TI  - Attention-grabbing motion in the human brain.
AB  - Visual motion signals can be derived either through a lower-order mechanism in
      which motion detectors register changes in luminance over space and time or
      through a higher-order mechanism that tracks salient features as they change
      position. A recent fMRI study by Claeys and colleagues reports a new area of the
      human brain that responds to the motion of salient features and to apparent
      motion.

PMID- 14642269
TI  - Caught in the act: alpha-synuclein is the culprit in Parkinson's disease.
AB  - Previous reports on Parkinson's disease indicate that genetic mutations in alpha
      synuclein result in the aberrant accumulation of this protein, causing toxic gain
      of function leading to the development of Parkinson's. A recent report on the
      Iowan kindred, an extended pedigree with an autosomal dominant form of this
      disease, provides new mechanistic insight into Parkinson's disease by showing
      that an elevation in wild-type alpha-synuclein protein is sufficient to develop
      the early-onset form of the disorder. This review discusses how insights gained
      from these studies of alpha-synuclein may direct future research into Parkinson's
      disease.

PMID- 14642270
TI  - Tau phosphorylation, tangles, and neurodegeneration: the chicken or the egg?
AB  - Pathological aggregation of the microtubule-associated protein tau is a common
      feature of many neurodegenerative diseases. Although tau aggregation is
      associated with abnormal tau phosphorylation, the role of phosphorylation in the
      initiation of neurodegeneration has been unclear. Now, several animal models and
      data from human patients provide converging evidence that aberrant tau
      phosphorylation can cause a neurodegenerative phenotype similar to that seen in
      human neurodegenerative diseases.

PMID- 14642271
TI  - Retinoids run rampant: multiple roles during spinal cord and motor neuron
      development.
AB  - Learning how the incredible diversity of neurons in the vertebrate central
      nervous system (CNS) is generated is a central focus of developmental
      neuroscience. Three studies in the September 25, 2003, issue of Neuron bring us
      closer to this goal by revealing how the interplay between Fibroblast Growth
      Factor (FGF), retinoic acid (RA), and Sonic hedgehog (Shh) signaling regulate
      progression of spinal cord progenitor cells through various phases of development
      and specify particular types of spinal motor neurons (MNs).

PMID- 14642273
TI  - Aberrant Cdk5 activation by p25 triggers pathological events leading to
      neurodegeneration and neurofibrillary tangles.
AB  - Cyclin-dependent kinase 5 (Cdk5) and its regulatory subunit p35 are integral
      players in the proper development of the mammalian central nervous system.
      Proteolytic cleavage of p35 generates p25, leading to aberrant Cdk5 activation.
      The accumulation of p25 is implicated in several neurodegenerative diseases. In
      primary neurons, p25 causes apoptosis and tau hyperphosphorylation. Current mouse
      models expressing p25, however, fail to rigorously recapitulate these phenotypes
      in vivo. Here, we generated inducible transgenic mouse lines overexpressing p25
      in the postnatal forebrain. Induction of p25 preferentially directed Cdk5 to
      pathological substrates. These animals exhibited neuronal loss in the cortex and
      hippocampus, accompanied by forebrain atrophy, astrogliosis, and caspase-3
      activation. Endogenous tau was hyperphosphorylated at many epitopes, aggregated
      tau accumulated, and neurofibrillary pathology developed progressively in these
      animals. Our cumulative findings provide compelling evidence that in vivo
      deregulation of Cdk5 by p25 plays a causative role in neurodegeneration and the
      development of neurofibrillary pathology.

PMID- 14642274
TI  - Deregulation of dorsoventral patterning by FGF confers trilineage differentiation
      capacity on CNS stem cells in vitro.
AB  - The CNS is thought to develop from self-renewing stem cells that generate
      neurons, astrocytes, and oligodendrocytes. Other data, however, have suggested
      that astrocytes and oligodendrocytes are generated from separate progenitor
      populations. To reconcile these observations, we have prospectively isolated
      progenitors that do or do not express Olig2, an oligodendrocyte bHLH
      determination factor. Both Olig2(-) and Olig2(+) progenitors can behave as
      tripotential CNS stem cells (CNS-SCs) in vitro. Growth in FGF-2 causes induction
      of Olig2 in the former population, permitting oligodendrocyte differentiation;
      extinction of Olig2 in the latter cells permits astrocyte differentiation. The
      induction of Olig2 by FGF-2 is mediated, in part, via endogenous Sonic Hedgehog.
      These data indicate that clonogenic competence to generate neurons, astrocytes,
      and oligodendrocytes reflects a deregulation of dorsoventral patterning during
      expansion in vitro, raising the question of whether such trifatent cells actually
      exist in vivo.

PMID- 14642276
TI  - The orientation and molecular movement of a k(+) channel voltage-sensing domain.
AB  - Voltage-gated channels operate through the action of a voltage-sensing domain
      (membrane segments S1-S4) that controls the conformation of gates located in the
      pore domain (membrane segments S5-S6). Recent structural studies on the bacterial
      K(v)AP potassium channel have led to a new model of voltage sensing in which S4
      lies in the lipid at the channel periphery and moves through the membrane as a
      unit with a portion of S3. Here we describe accessibility probing and disulfide
      scanning experiments aimed at determining how well the K(v)AP model describes the
      Drosophila Shaker potassium channel. We find that the S1-S3 helices have one end
      that is externally exposed, S3 does not undergo a transmembrane motion, and S4
      lies in close apposition to the pore domain in the resting and activated state.

PMID- 14642275
TI  - FAK deficiency in cells contributing to the basal lamina results in cortical
      abnormalities resembling congenital muscular dystrophies.
AB  - Targeted deletion of focal adhesion kinase (fak) in the developing dorsal
      forebrain resulted in local disruptions of the cortical basement membrane located
      between the neuroepithelium and pia-meninges. At disruption sites, clusters of
      neurons invaded the marginal zone. Retraction of radial glial endfeet, midline
      fusion of brain hemispheres, and gliosis also occurred, similar to type II
      cobblestone lissencephaly as seen in congenital muscular dystrophy.
      Interestingly, targeted deletion of fak in neurons alone did not result in
      cortical ectopias, indicating that fak deletion from glia is required for
      neuronal mislocalization. Unexpectedly, fak deletion specifically from meningeal
      fibroblasts elicited similar cortical ectopias in vivo and altered laminin
      organization in vitro. These observations provide compelling evidence that FAK
      plays a key signaling role in cortical basement membrane assembly and/or
      remodeling. In addition, FAK is required within neurons during development
      because neuron-specific fak deletion alters dendritic morphology in the absence
      of lamination defects.

PMID- 14642277
TI  - Interaction between extracellular Hanatoxin and the resting conformation of the
      voltage-sensor paddle in Kv channels.
AB  - In voltage-activated potassium (Kv) channels, basic residues in S4 enable the
      voltage-sensing domain to move in response to membrane depolarization and thereby
      trigger the activation gate to open. In the X-ray structure of the KvAP channel,
      the S4 helix is located near the intracellular boundary of the membrane where it
      forms a "voltage-sensor paddle" motif with the S3b helix. It has been proposed
      that the paddle is lipid-exposed and that it translocates through the membrane as
      it activates. We studied the interaction of externally applied Hanatoxin with the
      voltage-sensor paddle in Kv channels and show that the toxin binds tightly even
      at negative voltages where the paddle is resting and the channel is closed.
      Moreover, measurements of gating charge movement suggest that Hanatoxin interacts
      with and stabilizes the resting paddle. These findings point to an extracellular
      location for the resting conformation of the voltage-sensor paddle and constrain
      its transmembrane movements during activation.

PMID- 14642278
TI  - Regulating the conducting states of a mammalian serotonin transporter.
AB  - Serotonin transporters (SERTs), sites of psychostimulant action, display multiple
      conducting states in expression systems. These include a substrate-independent
      transient conductance, two separate substrate-independent leak conductances
      associated with Na(+) and H(+), and a substrate-dependent conductance of variable
      stoichiometry, which exceeds that predicted from electroneutral substrate
      transport. The present data show that the SNARE protein syntaxin 1A binds the N
      terminal tail of SERT, and this interaction regulates two SERT-conducting states.
      First, substrate-induced currents are absent because Na(+) flux becomes strictly
      coupled to 5HT transport. Second, Na(+)-mediated leak currents are eliminated.
      These two SERT-conducting states are present endogenously in thalamocortical
      neurons, act to depolarize the membrane potential, and are modulated by molecules
      that disrupt SERT and syntaxin 1A interactions. These data show that protein
      interactions govern SERT activity and suggest that both cell excitability and
      psychostimulant-mediated effects will be dependent upon the state of association
      among SERT and its interacting partners.

PMID- 14642279
TI  - A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired
      in TRPC2 mutant mice: mechanism of pheromone transduction.
AB  - Vomeronasal sensory neurons play a crucial role in detecting pheromones, but the
      chemoelectrical transduction mechanism remains unclear and controversial. A major
      barrier to the resolution of this question has been the lack of an activation
      mechanism of a key transduction component, the TRPC2 channel. We have identified
      a Ca(2+)-permeable cation channel in vomeronasal neuron dendrites that is gated
      by the lipid messenger diacylglycerol (DAG), independently of Ca(2+) or protein
      kinase C. We demonstrate that ablation of the TRPC2 gene causes a severe deficit
      in the DAG-gated channel, indicating that TRPC2 encodes a principal subunit of
      this channel and that the primary electrical response to pheromones depends on
      DAG but not Ins(1,4,5)P(3), Ca(2+) stores, or arachidonic acid. Thus, a
      previously unanticipated mechanism involving direct channel opening by DAG
      underlies the transduction of sensory cues in the accessory olfactory system.

PMID- 14642280
TI  - Glial cells maintain synaptic structure and function and promote development of
      the neuromuscular junction in vivo.
AB  - To investigate the in vivo role of glial cells in synaptic function, maintenance,
      and development, we have developed an approach to selectively ablate perisynaptic
      Schwann cells (PSCs), the glial cells at the neuromuscular junction (NMJ), en
      masse from live frog muscles. In adults, following acute PSC ablation, synaptic
      structure and function were not altered. However, 1 week after PSC ablation,
      presynaptic function decreased by approximately half, while postsynaptic function
      was unchanged. Retraction of nerve terminals increased over 10-fold at PSC
      ablated NMJs. Furthermore, nerve-evoked muscle twitch tension was reduced. In
      tadpoles, repeated in vivo observations revealed that PSC processes lead nerve
      terminal growth. In the absence of PSCs, growth and addition of synapses was
      dramatically reduced, and existing synapses underwent widespread retraction. Our
      findings provide in vivo evidence that glial cells maintain presynaptic structure
      and function at adult synapses and are vital for the growth and stability of
      developing synapses.

PMID- 14642281
TI  - Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA
      receptors.
AB  - Activity-dependent targeting of NMDA receptors (NMDARs) is a key feature of
      synapse formation and plasticity. Although mechanisms for rapid trafficking of
      glutamate receptors have been identified, the molecular events underlying chronic
      accumulation or loss of synaptic NMDARs have remained unclear. Here we
      demonstrate that activity controls NMDAR synaptic accumulation by regulating
      forward trafficking at the endoplasmic reticulum (ER). ER export is accelerated
      by the alternatively spliced C2' domain of the NR1 subunit and slowed by the C2
      splice cassette. This mRNA splicing event at the C2/C2' site is activity
      dependent, with C2' variants predominating upon activity blockade and C2 variants
      abundant with increased activity. The switch to C2' accelerates NMDAR forward
      trafficking by enhancing recruitment of nascent NMDARs to ER exit sites via
      binding of a divaline motif within C2' to COPII coats. These results define a
      novel pathway underlying activity-dependent targeting of glutamate receptors,
      providing an unexpected mechanistic link between activity, mRNA splicing, and
      membrane trafficking during excitatory synapse modification.

PMID- 14642283
TI  - Long-lasting increases in intrinsic excitability triggered by inhibition.
AB  - Although experience-dependent changes in neural circuits are commonly assumed to
      be mediated by synaptic plasticity, modifications of intrinsic excitability may
      serve as a complementary mechanism. In whole-cell recordings from spontaneously
      firing vestibular nucleus neurons, brief periods of inhibitory synaptic
      stimulation or direct membrane hyperpolarization triggered long-lasting increases
      in spontaneous firing rates and firing responses to intracellular depolarization.
      These increases in excitability, termed firing rate potentiation, were induced by
      decreases in intracellular calcium and expressed as reductions in the sensitivity
      to the BK-type calcium-activated potassium channel blocker iberiotoxin. Firing
      rate potentiation is a novel form of cellular plasticity that could contribute to
      motor learning in the vestibulo-ocular reflex.

PMID- 14642282
TI  - Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression.
AB  - PSD-95 is a major scaffolding protein of the postsynaptic density, tethering NMDA
      and AMPA-type glutamate receptors to signaling proteins and the neuronal
      cytoskeleton. Here we show that PSD-95 is regulated by the ubiquitin-proteasome
      pathway. PSD-95 interacts with and is ubiquitinated by the E3 ligase Mdm2. In
      response to NMDA receptor activation, PSD-95 is ubiquitinated and rapidly removed
      from synaptic sites by proteasome-dependent degradation. Mutations that block PSD
      95 ubiquitination prevent NMDA-induced AMPA receptor endocytosis. Likewise,
      proteasome inhibitors prevent NMDA-induced AMPA receptor internalization and
      synaptically induced long-term depression. This is consistent with the notion
      that PSD-95 levels are an important determinant of AMPA receptor number at the
      synapse. These data suggest that ubiquitination of PSD-95 through an Mdm2
      mediated pathway is critical in regulating AMPA receptor surface expression
      during synaptic plasticity.

PMID- 14642284
TI  - Encoding of vibrissal active touch.
AB  - Mammals acquire much of their sensory information by actively moving their
      sensory organs. Yet, the principles of encoding by active sensing are not known.
      Here we investigated the encoding principles of active touch by rat whiskers
      (vibrissae). We induced artificial whisking in anesthetized rats and recorded
      from first-order neurons in the trigeminal ganglion. During active touch, first
      order trigeminal neurons presented a rich repertoire of responses, which could
      not be inferred from their responses to passive deflection stimuli. Individual
      neurons encoded four specific events: whisking, contact with object, pressure
      against object, and detachment from object. Whisking-responsive neurons fired at
      specific deflection angles, reporting the actual whiskers' position with high
      precision. Touch-responsive neurons encoded the horizontal coordinate of objects'
      position by spike timing. These findings suggest two specific encoding-decoding
      schemes for horizontal object position in the vibrissal system.

PMID- 14642285
TI  - A higher order motion region in human inferior parietal lobule: evidence from
      fMRI.
AB  - The proposal that motion is processed by multiple mechanisms in the human brain
      has received little anatomical support so far. Here, we compared higher- and
      lower-level motion processing in the human brain using functional magnetic
      resonance imaging. We observed activation of an inferior parietal lobule (IPL)
      motion region by isoluminant red-green gratings when saliency of one color was
      increased and by long-range apparent motion at 7 Hz but not 2 Hz. This higher
      order motion region represents the entire visual field, while traditional motion
      regions predominantly process contralateral motion. Our results suggest that
      there are two motion-processing systems in the human brain: a contralateral lower
      level luminance-based system, extending from hMT/V5+ into dorsal IPS and STS, and
      a bilateral higher-level saliency-based system in IPL.

PMID- 14642286
TI  - Functional imaging of perceptual learning in human primary and secondary
      somatosensory cortex.
AB  - Cellular mechanisms underlying synaptic plasticity are in line with the Hebbian
      concept. In contrast, data linking Hebbian learning to altered perception are
      rare. Combining functional magnetic resonance imaging with psychophysical tests,
      we studied cortical reorganization in primary and secondary somatosensory cortex
      (SI and SII) and the resulting changes of tactile perception before and after
      tactile coactivation, a simple type of Hebbian learning. Coactivation on the
      right index finger (IF) for 3 hr lowered its spatial discrimination threshold. In
      parallel, blood-oxygen level-dependent (BOLD) signals from the right IF
      representation in SI and SII enlarged. The individual threshold reduction was
      linearly correlated with the enlargement in SI, implying a close relation between
      altered discrimination and cortical reorganization. Controls consisting of a
      single-site stimulation did not affect thresholds and cortical maps. Accordingly,
      changes within distributed cortical networks based on Hebbian mechanisms alter
      the individual percept.

PMID- 14642287
TI  - Both of us disgusted in My insula: the common neural basis of seeing and feeling
      disgust.
AB  - What neural mechanism underlies the capacity to understand the emotions of
      others? Does this mechanism involve brain areas normally involved in experiencing
      the same emotion? We performed an fMRI study in which participants inhaled
      odorants producing a strong feeling of disgust. The same participants observed
      video clips showing the emotional facial expression of disgust. Observing such
      faces and feeling disgust activated the same sites in the anterior insula and to
      a lesser extent in the anterior cingulate cortex. Thus, as observing hand actions
      activates the observer's motor representation of that action, observing an
      emotion activates the neural representation of that emotion. This finding
      provides a unifying mechanism for understanding the behaviors of others.

PMID- 14642288
TI  - Components of visual prior entry.
AB  - The prior entry hypothesis contends that attention accelerates sensory
      processing, shortening the time to perception. Typical observations supporting
      the hypothesis may be explained equally well by response biases, changes in
      decision criteria, or sensory facilitation. In a series of experiments conducted
      to discriminate among the potential mechanisms, observers judged the simultaneity
      or temporal order of two stimuli, to one of which attention was oriented by
      exogenous, endogenous, gaze-directed, or multiple exogenous cues. The results
      suggest that prior entry effects are primarily caused by sensory facilitation and
      attentional modifications of the decision mechanism, with only a small part
      possibly due to an attention-dependent sensory acceleration.

PMID- 14642289
TI  - Spontaneous representations of small numbers of objects by rhesus macaques:
      examinations of content and format.
AB  - The project of comparative cognition benefits from common measures across
      species. We report here on five experiments using the violation of expectancy
      looking time measure with free-ranging rhesus macaques (Macaca mulatta), each
      designed to build on current knowledge concerning spontaneous representations of
      number. Each subject, tested in only one experimental condition, watched as
      eggplants were placed behind a screen one at a time, after which the screen was
      removed revealing an outcome that either matched or did not match the number
      placed there. Subjects looked longer at impossible than possible outcomes in
      1+1=2 or 3, 1 small+1 small=1 big or 2 small, 2+1=2 or 3, and 2+1=3 or 4
      conditions. They failed in 2+1+1=4 or 3 or 5 and in 1+1+1=2 or 3 conditions. This
      pattern of results closely matches that observed across several previous studies
      of human infants. The data allow us to test among four different proposals
      concerning the format and content of the mental representations underlying
      looking in these experiments. Object file representations are favored over: (i)
      low-level perceptual representations, (ii) representations of continuous
      variables such as volume or surface area, and (iii) analog magnitude
      representations of number. We conclude by considering exactly how the object
      tracking system revealed in these and other related experiments does and does not
      represent number, and how it might be one evolutionary precursor of the human
      specific system of number representations.

PMID- 14642290
TI  - Spatial updating of environments described in texts.
AB  - People update egocentric spatial relations in an effortless and on-line manner
      when they move in the environment, but not when they only imagine themselves
      moving. In contrast to previous studies, the present experiments examined
      egocentric updating with spatial scenes that were encoded linguistically instead
      of perceived directly. Experiment 1 demonstrated that, regardless of the mode of
      rotation (physical or imagined), egocentric updating takes place in a deliberate
      and backward fashion when the locations of objects are anchored in a mental
      framework. Experiment 2 involved only imagined rotations and showed that results
      remained unchanged when spatial labels were removed from the scene descriptions.
      Experiment 3 provided evidence that physical rotations--but not imagined
      rotations--lead to on-line updating of egocentric relations, provided that the
      objects of the scene are represented in a sensorimotor framework. The present
      results suggest that physical movements and sensorimotor encoding are both
      prerequisites of effortless egocentric updating.

PMID- 14642291
TI  - Developmental continuity in the processes that underlie spatial recall.
AB  - This study investigated whether children's spatial recall performance shows three
      separable characteristics: (1) biases away from symmetry axes (geometric
      effects); (2) systematic drift over delays; and (3) biases toward the exemplar
      distribution experienced in the task (experience-dependent effects). In
      Experiment 1, the location of one target within each geometric category was
      varied. Children's responses showed biases away from a midline axis that
      increased over delays. In Experiment 2, multiple targets were placed within each
      category at the same locations used in Experiment 1. After removing geometric
      effects, 6-year-olds'--but not 11-year-olds'--responses were biased toward the
      average remembered location over learning. In Experiment 3, children responded to
      one target more frequently than the others. Both 6- and 11-year-olds showed
      biases toward the most frequent target over learning. These results provide a
      bridge between the performance of younger children and adults, demonstrating
      continuity in the processes that underlie spatial memory abilities across
      development.

PMID- 14642292
TI  - Midazolam amnesia and retrieval from semantic memory: Developing methods to test
      theories of implicit memory.
AB  - Studies of organic anterograde amnesia have been central to the development of
      theories of implicit memory. Pharmacological amnesia provides an additional
      method for exploring implicit memory, allowing for the experimental manipulation
      of amnesia and the testing of more participants. A significant concern with
      pharmacological amnesia is whether its cognitive effects are specific to explicit
      memory. The current research examines the effects of the benzodiazepine,
      midazolam, on retrieval from semantic memory and encoding in explicit memory. We
      focus on midazolam because it holds significant advantages over other
      benzodiazepines in inducing pharmacological amnesia and prior research suggests
      it may be useful for testing theories of implicit memory. Our results demonstrate
      that midazolam does not impair accuracy of retrieval from semantic categories,
      even when it produces anterograde amnesia for retrieved category items on a later
      recall test. These results suggest ways midazolam can be used to help test
      theories of implicit memory.

PMID- 14642293
TI  - Category-specific visual agnosia: lesion to semantic memory versus extra-lesional
      variables in a case study and a connectionist model.
AB  - There is a current debate on the causes of category-specific agnosia. The aim of
      this study was to examine the effects of lesional and extra-lesional variables on
      object recognition. Extra-lesional variables, such as visual complexity or
      familiarity, are factors that influence recognition. Using a connectionist model
      based on study, we provide evidence that extra-lesional variables can yield
      dissociations in the recognition rate of different categories. Furthermore, it is
      shown that lesional and extra-lesional variables can interact (p < .01) when both
      are simultaneously modeled. Category-specific agnosia might thus result from
      complex interactions.

PMID- 14642294
TI  - Cognition and affective style: Individual differences in brain electrical
      activity during spatial and verbal tasks.
AB  - Relations between brain electrical activity and performance on two cognitive
      tasks were examined in a normal population selected to be high on self-reported
      measures of Positive or Negative Affectivity. Twenty-five right-handed women,
      from an original pool of 308 college undergraduates, were the participants. EEG
      was recorded during baseline and during psychometrically matched spatial and
      verbal tasks. As predicted, participants who were high in Positive Affectivity
      performed equally well on the verbal and spatial tasks, while participants who
      were high in Negative Affectivity had spatial scores that were lower than their
      verbal scores. There were no group differences in baseline EEG. Both groups
      exhibited left central activation (i.e., alpha suppression) during the verbal and
      spatial tasks. When EEG data were analyzed separately for the group high in
      Positive Affectivity, there was evidence of parietal activation for the spatial
      task relative to the verbal task. The EEG data for the group high in Negative
      Affectivity had comparable EEG power values during verbal and spatial tasks at
      parietal scalp locations. These data suggest that, within a selected normal
      population, differences in affective style may interact with cognitive
      performance and with the brain electrical activity associated with that
      performance.

PMID- 14642295
TI  - The valence-specific laterality effect in free viewing conditions: The influence
      of sex, handedness, and response bias.
AB  - The right hemisphere has often been viewed as having a dominant role in the
      processing of emotional information. Other evidence indicates that both
      hemispheres process emotional information but their involvement is valence
      specific, with the right hemisphere dealing with negative emotions and the left
      hemisphere preferentially processing positive emotions. This has been found under
      both restricted (Reuter-Lorenz & Davidson, 1981) and free viewing conditions
      (Jansari, Tranel, & Adophs, 2000). It remains unclear whether the valence
      specific laterality effect is also sex specific or is influenced by the
      handedness of participants. To explore this issue we repeated Jansari et al.'s
      free-viewing laterality task with 78 participants. We found a valence-specific
      laterality effect in women but not men, with women discriminating negative
      emotional expressions more accurately when the face was presented on the left
      hand side and discriminating positive emotions more accurately when those faces
      were presented on the right-hand side. These results indicate that under free
      viewing conditions women are more lateralised for the processing of facial
      emotion than are men. Handedness did not affect the lateralised processing of
      facial emotion. Finally, participants demonstrated a response bias on control
      trials, where facial emotion did not differ between the faces. Participants
      selected the left-hand side more frequently when they believed the expression was
      negative and the right-hand side more frequently when they believed the
      expression was positive. This response bias can cause a spurious valence-specific
      laterality effect which might have contributed to the conflicting findings within
      the literature.

PMID- 14642296
TI  - Ear advantage and consonance of dichotic pitch intervals in absolute-pitch
      possessors.
AB  - Left-right asymmetry in the central processing of musical consonance was
      investigated by dichotic listening tasks. Two piano tones paired at various pitch
      intervals (1-11 semitones) were presented one note in each ear to twenty absolute
      pitch possessors. As a result, a weak overall trend for left ear advantage (LEA)
      was found, as is characteristic of trained musicians. Second, pitches of
      dissonant intervals were more difficult to identify than those of consonant
      intervals. Finally, the LEA was greater with dissonant intervals than with
      consonant intervals. As the tones were dichotically presented, the results
      indicated that the central auditory system could distinguish between consonant
      and dissonant intervals without initial processing of pitch-pitch relations in
      the cochlea.

PMID- 14642297
TI  - The thalamus and basal ganglia: What is exactly where? A reply to
      'Neuropsychological consequences of right thalamic injury: case study and
      review,' MJ Summers, Brain and Cognition 50 (2002).
AB  - The present paper re-analyzes anatomical and clinical data of a previous case
      report (Summer, 2002). In this case study, a patient with severe
      neuropsychological and behavioral impairments is described and it is claimed that
      these impairments are causally linked to an right thalamic lesion. A simple
      method how to perform a lesion analysis is introduced which shows that PD's
      lesion was a striatocapsular hematoma, and not a thalamic bleeding. The results
      of this anatomical re-analysis challenge the original behavioral-lesion
      hypothesis and emphasize the importance to provide appropriate data on brain
      lesions and clinical findings in neuropsychological case reports.

PMID- 14642298
TI  - To imitate or not to imitate? How the brain can do it, that is the question!
AB  - In this paper the authors discuss the most prominent views addressing the issue
      of how we imitate actions. It is argued that the existing theories lay along a
      continuum, with the direct mapping approach at one end (Butterworth, 1990; Gray,
      Neisser, Shapiro, & Kouns, 1991) the Active Intermodal Matching approach (Melzoff
      & Moore, 1997) in the middle, and the goal-directed theory (Bekkering,
      Wohlshager, & Gattis, 2000) and the dual route theory (Rumiati & Tessari, 2002)
      at the opposite end. Interestingly the latter views can account for behaviors
      that cannot be explained by invoking the direct mapping or the Active Intermodal
      Matching approach.

PMID- 14642299
TI  - Pantomimes are special gestures which rely on working memory.
AB  - The case of a patient is reported who presented consistently with overt deficits
      in producing pantomimes in the absence of any other deficits in producing
      meaningful gestures. This pattern of spared and impaired abilities is difficult
      to reconcile with the current layout of cognitive models for praxis. This patient
      also showed clear impairment in a dual-task paradigm, a test taxing the co
      ordination aspect of working memory, though performed normally in a series of
      other neuropsychological measures assessing language, visuo-spatial functions,
      reasoning function, and executive function. A specific working memory impairment
      associated with a deficit of pantomiming in the absence of any other disorders in
      the production of meaningful gestures suggested a way to modify the model to
      account for the data. Pantomimes are a particular category of gestures,
      meaningful, yet novel. We posit that by their very nature they call for the
      intervention of a mechanism to integrate and synthesise perceptual inputs
      together with information made available from the action semantics (knowledge
      about objects and functions) and the output lexicon (stored procedural
      programmes). This processing stage conceived as a temporary workspace where
      gesture information is actively manipulated, would generate new motor programmes
      to carry out pantomimes. The model of gesture production is refined to include
      this workspace.

PMID- 14642300
TI  - Motor facilitation following action observation: a behavioural study in
      prehensile action.
AB  - Previous research has shown that the observation of actions and the execution of
      actions activate common neural systems. More recently, we have presented data
      showing that action observation of prehension primes subsequent execution
      (Castiello, Lusher, Mari, Edwards, & Humphreys, 2002). In the current paper we
      examined action priming under conditions in which the size of the prime did not
      predict the size of the target (only 20% of trials were valid). We demonstrated
      reliable priming under these conditions, consistent with the effect occurring
      automatically. In addition, we show priming even when observers saw just the
      object rather than the object and a reaching action on the prime trial. We
      discuss the findings in relation to the role of mirror neurons and object
      affordances.

PMID- 14642301
TI  - Off-line authorship effects in action perception.
AB  - Does the perception of our actions differ from the perception of other
      individuals' actions when we observe them, like other individual's actions, in an
      offline perspective? Previous studies, using recognition as well as prediction
      judgments, suggest that it does even if the stimulus information is reduced to a
      single moving point-light. Here, we assessed whether this difference also affects
      the timing of actions. This was tested in two experiments, using a specific
      synchronization task. After some practice, self-generated action events were
      anticipated faster than other action events, provided that the anticipation could
      not be accomplished sufficiently well on the basis of easily detectable cues. The
      results are discussed with regard to the previous findings of off-line authorship
      effects in action perception.

PMID- 14642302
TI  - New insights on sensorimotor integration: from hand action to speech perception.
AB  - In the last two decades the integrative role of the frontal premotor cortex (a
      mosaic of agranular/disgranular areas lying in front of the primary motor cortex)
      have been more and more elucidated. Among its various functions, sensorimotor
      transformation, and action representation storage, also for nonstrictly motor
      purposes, are the most intriguing properties of this region, as shown by several
      researches. In this article we will mainly focus on the ventro-rostral part of
      the monkey premotor cortex (area F5) in which visual information describing
      objects and others' acting hands are associated with goal-directed motor
      representations of hand movements. We will describe the main characteristics of
      F5 premotor neurons and we will provide evidence in favor of a parallelism
      between monkeys and humans on the basis of new experimental observations.
      Finally, we will present some data indicating that, both in humans and in
      monkeys, action-related sensorimotor transformations are not restricted to visual
      information but concern also acoustic information.

PMID- 14642303
TI  - From cells to signaling cascades: manipulation of innate immunity by Toxoplasma
      gondii.
AB  - The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus
      for cell-mediated immunity, and IL-12-dependent IFN-gamma induction is vital in
      resistance to the parasite. Dendritic cells, neutrophils and macrophages are
      important sources of IL-12 during infection. T. gondii possesses two mechanisms
      for triggering IL-12. One is dependent upon the common adaptor protein MyD88, and
      is likely to involve Toll-like receptors. The other is a more unusual pathway
      that involves triggering through CCR5 by a parasite cyclophilin molecule.
      Countering these potent pro-inflammatory activities, T. gondii has several
      mechanisms to down-regulate immunity. Intracellular infection causes a blockade
      in the NFkappaB macrophage signaling pathway, correlating with reduced capacity
      for IL-12 and TNF-alpha production. The parasite also prevents STAT1 activity,
      resulting in decreased levels of IFN-gamma-stimulated MHC surface antigen
      expression. Furthermore, infection also induces resistance to apoptosis through
      inhibition of caspase activity. Extracellular pathways of suppression involve
      soluble mediators such as IL-10 and lipoxins that have potent IL-12 down
      regulatory effects. The balance of pro-inflammatory and anti-inflammatory
      signaling which T. gondii engages is likely dictated by requirements for a stable
      host-parasite interaction. First, there is a need for Toxoplasma to induce an
      immune response robust enough to allow host survival and establish long-term
      chronic infection. Second, the parasite must avoid immune-elimination and
      induction of pro-inflammatory pathology that can cause lethality if unchecked.
      The widespread distribution of T. gondii and the normally innocuous nature of
      infection indicate the skill with which the parasite achieves the two seemingly
      contrary goals.

PMID- 14642304
TI  - Avian HSC emergence, migration, and commitment toward the T cell lineage.
AB  - To date three sites of emergence of hemopoietin cells have been identified during
      early avian development: the yolk sac, the intraaortic clusters and recently the
      allantois. However, the contributions of the hematopoietic stem cell (HSC)
      populations generated by these different sites to definitive hematopoiesis and
      their migration routes are not fully unraveled. Experimental embryology as well
      as the establishment of the genetic cascades involved in HSC emergence help now
      to draw a better scheme of these processes.

PMID- 14642305
TI  - Porin of Shigella dysenteriae enhances mRNA levels for Toll-like receptor 2 and
      MyD88, up-regulates CD80 of murine macrophage, and induces the release of
      interleukin-12.
AB  - Sera of patients convalescing from shigellosis reacted strongly and specifically
      with the 38,000 Da monomer of porin of Shigella dysenteriae type 1. Since human,
      the only natural host of S. dysenteriae type 1, recognized the protein through
      humoral immune response, it is of great significance to study the surface-exposed
      outer membrane antigen as an adjuvant. Porin treatment of CD11b+ peritoneal
      cavity (PerC) MPhi of BALB/c mouse was found to up-regulate CD80 on cell surface
      and had no effect on CD86 expression. The surface expression of CD80 got
      increased by 1.6-fold in the presence of gamma interferon (IFN-gamma) supporting
      selective regulation of the B7-1 (CD80) member of the B7 family. MPhi released
      7.25 pg of interleukin-12 (IL-12) in the presence of porin. The protein in
      combination with IFN-gamma augmented profoundly the release of IL-12 by 2.6-fold.
      Porin-mediated induction of IL-12 release would therefore influence Th1-type
      response, known to be preferentially triggered due to up-regulation of CD80
      expression. Treatment of PerC MPhi by the protein showed an increase of mRNA for
      both Toll-like receptor (TLR)2 and myeloid differentiation factor 88 (MyD88) by 2
      and 2.3-fold respectively, emphasizing that TLR2 is essential for recognition of
      S. dysenteriae type 1 porin. Understanding the mechanism of adjuvanticity of
      porin of S. dysenteriae type 1 is a necessary step towards the development of a
      better adjuvant against shigellosis.

PMID- 14642306
TI  - Polyene and cytokine treatment of experimental aspergillosis.
AB  - The aim of the present study was to assess the efficacy of amphotericin B (AMB),
      AMB-intralipid admixture (AMB-IL) or nystatin-IL formulation (Ny-IL) in
      combination with granulocyte colony stimulating factor (G-CSF) in treatment of
      experimental murine aspergillosis. ICR mice were immunosuppressed by
      cyclophosphamide and 3 days later inoculated intravenously (i.v.) with
      Aspergillus fumigatus. Treatment was initiated 2 h later and administered for 5
      consecutive days (polyenes, i.v.; G-CSF, intraperitoneally). Combination therapy,
      particularly G-CSF with AMB or AMB-IL, significantly increased the survival rate
      (up to 87.3%) and prolonged the mean survival time (MST) (up to 28.8 days) in
      comparison to untreated controls (0% survival, MST 6.7 days) and to treatment
      with polyenes alone (up to 51.5% survival, MST 18.4 days). These data indicate
      that combination therapy could be beneficial for management of disseminated
      aspergillosis in humans.

PMID- 14642307
TI  - Immunomodulation by Yersinia enterocolitica: comparison of live and heat-killed
      bacteria.
AB  - This study compared the immunomodulating properties of viable and killed Yersinia
      enterocolitica O9 in BALB/c mice. At 10 days after infection by the intragastric
      route, ex vivo assays showed a suppression of spleen cell proliferation in
      response to Salmonella lipopolysaccharide, concanavalin A and heat-killed
      yersiniae. Mice infected with Y. enterocolitica O9 for 10 days resisted the
      challenge with a lethal dose of Listeria monocytogenes. In contrast, intravenous
      administration of heat-killed yersiniae did not modify the ability of spleen
      cells to proliferate in response to lipopolysaccharide or concanavalin A, and
      proliferation in response to killed yersiniae was significantly increased. By 3
      days after administration of a single dose of heat-killed yersiniae, the
      resistance of mice to L. monocytogenes challenge was significantly increased. Our
      findings show profound differences in immunomodulation by viable and heat-killed
      yersiniae, but suggest that killed yersiniae retain interesting immunomodulating
      properties.

PMID- 14642308
TI  - Large-scale validation of a latex agglutination test for diagnosis of
      tuberculosis.
AB  - Large-scale validation of a simple latex agglutination test for the diagnosis of
      tuberculosis is described. Soluble antigens extracted from a non-pathogenic
      saprophytic mycobacterium, Mycobacterium w, which shares antigenic determinants
      with Mycobacterium tuberculosis, were covalently linked to carboxylated
      polystyrene latex beads. Batch to batch reproducibility of coated latex was
      ensured. Latex reagents were standardized to overcome non-specific agglutination.
      Reagents of the test are stable for 1 year at 4 degrees C. A total of 1,058 serum
      samples of pulmonary and extrapulmonary tuberculosis patients or patients with
      other pulmonary diseases and healthy controls living in endemic areas were
      tested. Sensitivity of 94% for pulmonary tuberculosis and 87% for extrapulmonary
      tuberculosis was obtained. Specificity is 92.2% for healthy controls and patients
      with other respiratory diseases. We conclude that the latex agglutination test
      can be utilized for mass screening for both pulmonary and extrapulmonary
      tuberculosis where diagnosis by existing methods is much more difficult.

PMID- 14642309
TI  - DNA prime-protein boost immunization in monkeys: efficacy of a novel construct
      containing functional domains of Plasmodium cynomolgi CS and TRAP.
AB  - We report the efficacy of a bimodal immunization regimen that involved priming
      with naked DNA (multiple doses) followed by a booster with recombinant protein in
      rhesus monkeys with a chimeric construct containing the N-terminus of
      thrombospondin-related adhesive protein and the C-terminus of circumsporozoite
      protein of Plasmodium cynomolgi. The vaccinated animals developed high titer
      antibodies against the chimeric antigen, the two components of the hybrid and the
      native proteins of sporozoites. The peripheral blood mononuclear cells isolated
      from the vaccinated animals had significant in vitro T cell proliferation
      activity when stimulated with the recombinant chimeric protein. Furthermore,
      following challenge with 1000 P. cynomolgi sporozoites, the peak and total
      parasitemia were significantly lower in vaccinated animals than in the control
      animals.

PMID- 14642310
TI  - Induced Helicobacter pylori vacuolating cytotoxin VacA expression after initial
      colonisation of human gastric epithelial cells.
AB  - To study the effect of initial colonisation on Helicobacter pylori gene
      expression, altered H. pylori gene transcription during co-culture with human
      gastric epithelial cells was determined. Therefore, an insertion library of H.
      pylori with random chromosomal fusions to a promoterless cat gene was grown in
      the presence of HM02 gastric epithelial cells and varying levels of
      chloramphenicol. One H. pylori transformant was chloramphenicol-resistant in the
      presence, but chloramphenicol-susceptible in the absence of gastric epithelial
      HM02 cells. This transformant had the promoterless cat gene inserted into the
      HP0887 gene, which encodes the vacuolating cytotoxin VacA, an important virulence
      factor of H. pylori. Reverse transcriptase polymerase chain reaction on cDNA of
      this transformant confirmed vacA upregulation near HM02 cells. These results show
      the applicability of this technique to study H. pylori gene regulation in its
      natural environment.

PMID- 14642311
TI  - Phytomonas serpens, a tomato parasite, shares antigens with Trypanosoma cruzi
      that are recognized by human sera and induce protective immunity in mice.
AB  - The immune cross-reactivity between Trypanosoma cruzi, the protozoan that causes
      Chagas' disease, and Phytomonas serpens, a trypanosomatid that infects tomatoes,
      was studied. Sera from patients with Chagas' disease presented a strong
      reactivity with P. serpens antigens by conventional serological assays such as
      indirect immunofluorescence (IIF) and direct agglutination test (DAT), confirmed
      after cross-absorption experiments. The results show that this protozoan is
      highly immunogenic and that rabbit and mouse hyperimmune serum raised against T.
      cruzi or P. serpens was able to recognize both T. cruzi and P. serpens antigens
      in immunofluorescence and agglutination assays. The antigenic cross-reactivity
      between T. cruzi and P. serpens was also demonstrated in vivo. BALB/c mice
      immunized by the intraperitoneal or oral route with P. serpens and later
      challenged with a lethal inoculum of T. cruzi blood forms showed a significant
      decrease in parasitemia and increase in survival compared to controls. A
      practical implication of these findings is that the ingestion by humans or
      animals of living plant trypanosomatids present in naturally infected edible
      fruits could potentially prime the immune response to T. cruzi antigens and
      interfere with the development of T. cruzi infection.

PMID- 14642312
TI  - Epitope mapping of pneumococcal surface protein A of strain Rx1 using monoclonal
      antibodies and molecular structure modelling.
AB  - Pneumococcal surface protein A (PspA) is an antigenic variable vaccine candidate
      of Streptococcus pneumoniae. Epitope similarities between PspA from the American
      vaccine candidate strain Rx1 and Norwegian clinical isolates were studied using
      PspA specific monoclonal antibodies (mAbs) made against clinical Norwegian
      strains. Using recombinant PspA/Rx1 fragments and immunoblotting the epitopes for
      mAbs were mapped to two regions of amino acids, 1-67 and 67-236. The discovered
      epitopes were visualized by modelling of the PspA:Fab part of mAb in three
      dimensions. Flow cytometric analysis showed that the epitopes for majority of
      mAbs were accessible for antibody binding on live pneumococci. Also, the epitopes
      for majority of the mAbs are widely expressed among clinical Norwegian isolates.

PMID- 14642313
TI  - The effects of streptozotocin-induced diabetes on brucellosis of rats.
AB  - It is believed that an infection is more common and runs a more protracted course
      in people with diabetes. In clinical practice, it is important to be aware of
      these associations, as the prognosis is often dependent upon prompt recognition
      and appropriate treatment. To show the course of brucellosis in the diabetic
      state, a model of Brucella melitensis infection was used in the setting of
      streptozotocin-induced diabetes in rat. B. melitensis infection proceeded more
      severely in diabetic rats and the severity of diabetes affected the prognosis.
      However, no association was found between B. melitensis and insulin using in
      vitro and in vivo experiments. Our study illustrates that B. melitensis infection
      in diabetes should be taken seriously.

PMID- 14642315
TI  - Perinatal health indicators for Europe: an introduction to the PERISTAT project.

PMID- 14642314
TI  - Extensive MHC class I-restricted CD8 T lymphocyte responses against various yeast
      genera in humans.
AB  - The human cellular immune response against 14 distantly related yeast species was
      analyzed by intracellular cytokine staining of lymphocytes after ex vivo
      stimulation of whole blood. While the CD4 T cell response was marginal, extensive
      MHC class I-restricted CD8 T cell responses were detected against a number of
      species including spoiling, environmental and human pathogenic yeasts. The yeast
      specific CD8 T cells expressed interferon-gamma but lacked expression of CD27 and
      CCR7, indicating that they were end-differentiated effector memory cells. Mainly
      intact yeast cells rather than spheroplasts were able to induce cytokine
      expression in T cells demonstrating that the dominant immunogens were located in
      the yeast cell wall. Together these data underline the importance of the cellular
      immune response in protecting humans against yeast and fungal infections. And,
      from another perspective, recombinant yeast suggests itself as a potential
      vaccine candidate to efficiently induce antigen-specific CD8 T cell responses.

PMID- 14642316
TI  - Selecting an indicator set for monitoring and evaluating perinatal health in
      Europe: criteria, methods and results from the PERISTAT project.
AB  - The PERISTAT project was charged with developing an indicator set for monitoring
      and describing perinatal health in Europe as part of the European Commission's
      Health Monitoring Programme, run by the Directorate General for Health and
      Consumer Protection (DG-SANCO), which is working towards the establishment of a
      comprehensive health monitoring system at the community level. To develop its
      recommendations, the PERISTAT project carried out an extensive review of existing
      perinatal health indicators and then implemented a DELPHI consensus process with
      its scientific advisory committee, a panel composed of clinicians,
      epidemiologists and statisticians, as well as with a panel of midwives. Consensus
      was achieved on 10 core and 23 recommended indicators using methods that drew on
      and consolidated previous work in this field. Twelve of these indicators were
      targeted for further development and the other 21 for immediate implementation. A
      feasibility study, reported in the rest of this issue, was put into place to
      assess these recommendations.

PMID- 14642317
TI  - The availability of perinatal health indicators in Europe.
AB  - This paper uses the results of the PERISTAT feasibility study to assess the
      extent to which the participating countries of Europe were able to provide data
      to construct the core and recommended indicators of perinatal health defined in
      the project. After describing the approaches used for data collection in
      participating countries, this paper describes the extent to which they were able
      to provide the data requested to construct the indicators. It documents data
      sources within each country and their characteristics. The paper then discusses
      influences on the agenda, particularly the extent to which data collection occurs
      as a by-product of other processes such as civil registration and the
      administration of health care and how these processes can both enable and impede
      data collection. It closes by suggesting how data collection in Europe can be
      improved in order to widen the scope of the agenda for compiling perinatal
      indicators.

PMID- 14642318
TI  - Methodological difficulties in the comparison of indicators of perinatal health
      across Europe.
AB  - The main purpose of this article is to point out common pitfalls that can confuse
      comparative analyses of indicators of perinatal health and to discuss ways to
      overcome or minimize these difficulties. The challenge is to distinguish 'real'
      variations in the value of an indicator from variations due to differences in
      registration practices and definitions and from random variation. The first
      section presents the major properties that are desirable in indicators of
      perinatal health status and perinatal health care in Europe to be used for
      comparative purposes. The second section provides specific examples of the types
      of methodological difficulties encountered in European cross-country comparisons
      due to variations in the definition, measurement and construction of indicators.
      The conclusion discusses the PERISTAT project's responses to these difficulties
      and how these methodological constraints impact on the selection of an
      appropriate indicator set for Europe today.

PMID- 14642319
TI  - Characteristics of the childbearing population in Europe.
AB  - OBJECTIVE: To report the distribution and availability of the indicators
      describing the population of childbearing women in Europe and to assess the
      impact of the difference in the distribution of two of these indicators (age and
      multiple births) on some outcome indicators. METHODS: The six PERISTAT indicators
      of population characteristics were computed using data from a survey of data
      providers in Europe. For maternal age and multiple births, the impact on health
      outcome was simulated for the extremes of the distribution using indirect
      standardised rates. RESULTS: Data availability is good for basic demographic
      indicators (age, parity, multiple births), but less complete for indicators of
      social characteristics (education, smoking, country of birth). Further, common
      definitions are not used for the latter. Simulations of the impact of maternal
      age on health outcome found that variation in the maternal age distribution may
      cause trisomy 21 rates to differ by nearly 20% and maternal mortality ratios by
      nearly 50%. CONCLUSION: Indicators of basic population characteristics are not
      collected routinely in every country. The crude distribution of these indicators
      is essential for international comparisons. Interpretation of comparative data
      would be improved by collection of health outcomes and service use by maternal
      characteristics.

PMID- 14642320
TI  - European indicators of health care during pregnancy, delivery and the postpartum
      period.
AB  - OBJECTIVES: To describe variation across Europe in PERISTAT indicators of health
      care in the perinatal period, and to assess the comparability of these
      indicators. STUDY DESIGN: The PERISTAT feasibility study provides the source for
      this descriptive study, covering 15 European countries. Comparative analysis
      includes descriptions of births following management of sub-fertility, timing of
      first antenatal visit, onset of labour, mode of delivery, place of birth, preterm
      births in units without NICU, and breast-feeding uptake. RESULTS: There is broad
      variation in the availability to provide data on perinatal indicators, and in
      perinatal health care across the European Union. CONCLUSIONS: This paper
      describes the challenge of identifying indicators that are meaningful and robust
      for the full distribution of health care systems represented in the European
      Union. Further work is needed to ensure that the implementation of each indicator
      is comparable across member states.

PMID- 14642321
TI  - Indicators of fetal and infant health outcomes.
AB  - OBJECTIVE: To assess the ability of the member states of the European Union to
      produce the indicators recommended by the PERISTAT project on perinatal health
      indicators and to provide an overview of fetal and infant health outcomes for
      these countries according to the information now available. METHODS: We used data
      from the PERISTAT survey of data providers to compute PERISTAT indicators of
      fetal and infant health. RESULTS: National data on fetal mortality are available
      for all countries, but vary in their definitions. To adjust for these differences
      in definition, PERISTAT recommends presenting rates by gestational age and birth
      weight. Not all countries can provide neonatal mortality data by gestational age,
      birth weight or plurality, as recommended by PERISTAT. Few countries in Europe
      can report infant mortality rates by birth weight and gestational age. The other
      recommended indicators are available to varying degrees. CONCLUSIONS: This
      overview, which shows that Europe can produce a variety of indicators for
      monitoring the health of its new-borns, indicates that some key dimensions of
      perinatal health cannot now be measured with routine health statistics and
      reveals important disparities in health outcomes throughout Europe. For most
      indicators, the highest values are between 50 and 100% higher than the lowest
      values. The reasons for these variations and their importance for the
      surveillance of perinatal health are discussed.

PMID- 14642322
TI  - Maternal health outcomes in Europe.
AB  - OBJECTIVES: To use PERISTAT data on indicators of maternal mortality and
      morbidity to explore maternal health outcomes in Europe, and to discuss the
      implications of variations in the data sources for these indicators. STUDY
      DESIGN: The PERISTAT feasibility study provides the source for this descriptive
      study, covering 15 European countries. Maternal mortality ratios are calculated,
      and data to describe maternal mortality by age, cause of death and mode of
      delivery are pooled for the countries that provided data. RESULTS: Data presented
      show an increased risk of maternal death among older mothers and for caesarean
      sections compared with other modes of delivery, and the three most prevalent
      causes of maternal deaths reported were embolism, hypertensive diseases of
      pregnancy, and haemorrhage. CONCLUSIONS: Variations in maternal mortality ratios
      reflect different data sources with varying levels of ascertainment in addition
      to differences in the number of maternal deaths. Further development is needed to
      construct comparable indicators of maternal morbidity.

PMID- 14642323
TI  - Fullerene derivatives: an attractive tool for biological applications.
AB  - The fullerene family, and especially C60, has very appealing photo-, electro
      chemical and physical properties, which can be exploited in many and different
      biological fields. Fullerene is able to fit inside the hydrophobic cavity of HIV
      proteases, inhibiting the access of substrates to the catalytic site of the
      enzyme. It can be used as radical scavenger; in fact some water-soluble
      derivatives are able to reduce ROS concentrations. At the same time, if exposed
      to light, fullerene can produce singlet oxygen in high quantum yields. This
      action, together with the direct electron transfer from excited state of
      fullerene and DNA bases, can be used to cleave DNA. In this review we report the
      most recent aspects of fullerene biological applications.

PMID- 14642324
TI  - Comparison of the efficiency of various methods for the synthesis of models of
      metabolites: example of 4a-methylhexahydronaphtalenones.
AB  - In order to examine the biotransformations of xenobiotics, it is essential to
      realize studies of metabolism of drugs in living animals. It is generally
      difficult to extract quantitatively the metabolites from biological media or
      excreta. Alternative methods have then been developed. Application of such
      techniques to 4a-methylhexahydronaphthalenones, which constitute starting
      material for the stereospecific synthesis of terpenoids or steroids, is
      particularly demonstrative. By biosynthetical ways, it was not possible to access
      with good yields to all the metabolites obtained in vivo. A novel methodology,
      based on the use of a manganoporphyrin catalyst, allowed to synthesize large
      amounts of several models of metabolites corresponding to those which had been
      isolated in living rats. Only one of the metabolites obtained in vivo could not
      be synthesized by this biomimetic system. This proved that alternative methods
      are precious to obtain models with good yields, but need to be validated by
      controls in living animals.

PMID- 14642325
TI  - A quantum chemical and statistical study of flavonoid compounds (flavones) with
      anti-HIV activity.
AB  - The molecular orbital semi-empirical method AM1 was employed to calculate a set
      of molecular properties (variables) of 22 flavonoid compounds (flavones) with
      anti-HIV-1 activity and nine new compounds were proposed for anti-HIV-1 activity
      prediction. Pattern recognition techniques, principal component analysis (PCA),
      hierarchical cluster analysis (HCA), stepwise discriminant analysis (SDA) and K
      nearest neighbor (KNN), were employed in order to reduce dimensionality and
      investigate which subset of variables could be more effective for classifying the
      flavones according to their degree of anti-HIV-1 activity. The PCA, HCA, SDA and
      KNN studies showed that the variables log P (partition coefficient), molecular
      volume (VOL) and electron affinity (EA) are responsible for the separation
      between anti-HIV-1 active and inactive compounds. The prediction study was done
      with a new set of nine analog compounds by using the PCA, HCA, SDA and KNN
      methods and only one of them was predicted as active against HIV-1.

PMID- 14642326
TI  - Quantitative relationship between rat intestinal absorption and Abraham
      descriptors.
AB  - Literature data on the intestinal absorption of 158 drug and drug-like compounds
      in rats have been collected, and Abraham descriptors for the set of drugs have
      been calculated using the method of Platts and Abraham et al. Results show that
      there is a significant relationship between rat intestinal absorption and the
      Abraham descriptors. In agreement with the human intestinal absorption model, the
      dominant descriptors in the rat model are the drug hydrogen bond acidity and
      basicity. In order to compare the absorption models in humans and rats, the
      absorption model developed from rats was used to predict the absorption in
      humans. The rat intestinal absorption model is similar to the human absorption
      model, and data on rats can effectively be used to predict human intestinal
      absorption.

PMID- 14642327
TI  - Synthesis and in vitro anti-protozoal activity of a series of benzotropolone
      derivatives incorporating endocyclic hydrazines.
AB  - The preparation and evaluation as potential anti-protozoal agents of molecules
      bearing an endocyclic hydrazine moiety is presented. The synthetic route to this
      new series of compounds is straightforward, involving a hetero Diels-Alder
      reaction between different benzotropolone esters and diethyl azodicarboxylate
      (DEAD). While they show limited or no in vitro activity against Leishmania
      donovani, Plasmodium falciparum and Trypanosoma brucei rhodesiense, several of
      the compounds have activities against Trypanosoma cruzi in the 15.8-41.0 microM
      range. These activities are comparable to that of benznidazole (IC50 6.0 microM),
      the main chemotherapy employed in the treatment of T. cruzi infections. In
      addition, all but one of the new bicyclic hydrazine esters are virtually non
      toxic, one of the most important drawbacks of currently available trypanocidal
      drugs.

PMID- 14642328
TI  - Polysubstituted pyrazoles, part 5. Synthesis of new 1-(4-chlorophenyl)-4-hydroxy
      1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived ring systems. A
      novel class of potential antitumor and anti-HCV agents.
AB  - A novel series of 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazole-3-carboxylic acid
      hydrazide analogs and some derived 4-substituted-1,2,4-triazolin-3-thiones, 2
      substituted-1,3,4-thiadiazole and 2-substituted-1,3,4-oxadiazoles has been
      synthesized. Ten of the newly synthesized compounds were selected by the National
      Cancer Institute (NCI)-in vitro-disease oriented antitumor screening to be
      evaluated for their antitumor activity. Seven compounds, namely 7a-c, 9, 11, 13
      and 14, exhibited potential and broad spectrum antitumor activity against most of
      the tested subpanel tumour cell lines (GI50<100 microM). Compounds 14 (GI50, TGI,
      and LC50 MG-MID values of 0.08, 15.8 and 64.6 microM, respectively) and 11 (GI50,
      TGI, and LC50 MG-MID values of 0.20, 11.7 and 87.1 microM, respectively) proved
      to be the most active members in this study with potential activity against all
      the tested subpanel tumour cell lines and particular effectiveness on the
      leukaemia subpanel at both the GI50 (0.03 and 0.09 microM, respectively) and the
      TGI levels (35.2 and 28.1 microM, respectively). Moreover, compound 14 exhibited
      a super sensitivity profile towards about 26 different cancer cell lines with
      GI50 values lying in the nanomolar concentration range (GI50 values<0.01 microM).
      In addition, compounds 2-5, 6a-d, 7a, 8-11, 12a, 13, 14 were investigated for
      their in vitro effect on the replication of hepatitis-C virus (HCV) in HepG2
      hepatocellular carcinoma cell line infected with the virus using the reverse
      transcription-polymerase chain reaction (RT-PCR) technique. The results revealed
      that compounds 2 and 5 were capable of inhibiting the replication of both the HCV
      RNA (+) and (-) strands at 10-100 microg mL(-1) concentration range.

PMID- 14642329
TI  - 3D-QSAR studies of indole derivatives as phosphodiesterase IV inhibitors.
AB  - The 3D-QSAR studies of some indole derivatives as phosphodiesterase (PDE) type IV
      inhibitors was performed by Comparative Molecular Field Analysis (CoMFA) and
      Comparative Molecular Similarity Indices Analysis (CoMSIA) methods to determine
      the factors required for the activity of these compounds. The global minimum
      energy conformer of the template molecule, 3 the most active molecule of the
      series, was obtained by simulated annealing method and used to build the
      structures of the molecules in the dataset. The CoMFA model produced
      statistically significant results with cross-validated and conventional
      correlation coefficients of 0.494 and 0.986 respectively. The combination of
      steric, electrostatic and hydrophobic fields in CoMSIA gave the best results with
      cross-validated and conventional correlation coefficients of 0.541 and 0.967
      respectively. The predictive ability of CoMFA and CoMSIA were determined using a
      test set of seven indole derivatives giving predictive correlation coefficients
      of 0.56 and 0.59 respectively indicating good predictive power. Further, the
      robustness of the models was verified by bootstrapping analysis. Based upon the
      information derived from CoMFA and CoMSIA, we have identified some key features
      that may be used to design new indole derivatives and predict their PDE IV
      affinities prior to synthesis.

PMID- 14642330
TI  - N6-cycloalkyl-2-phenyl-3-deaza-8-azaadenines: a new class of A1 adenosine
      receptor ligands. A comparison with the corresponding adenines and 8-azaadenines.
AB  - Several 9-benzyl-N6-cycloalkyl-2-phenyladenines, 9-benzyl-N6-cycloalkyl-2-phenyl
      8-azaadenines and 4-cycloalkylamino-1-benzyl-6-phenyl-1H-1,2,3-triazolo[4,5
      c]pyridines were prepared and assayed as A1 adenosine receptor ligands. The 1H
      1,2,3-triazolo[4,5-c]pyridines were obtained starting from N,N-diethyl-1-benzyl-4
      carboxyamido-5-methyl-1H-1,2,3-triazole by lithiation in anhydrous
      tetrahydrofurane in the presence of benzonitrile. The usual work up afforded the
      isolation of 1-benzyl-6-phenyl-1H-1,2,3-triazolo[4,5-c]pyridin-4-one which was
      treated with phosphorous oxychloride and cycloalkylamines. Some compounds showed
      high affinity and selectivity and the trend of Ki values corresponds to the
      series of 9-benzyl-N6-cycloalkyl-2-phenyladenines and 9-benzyl-N6-cycloalkyl-2
      phenyl-8-azaadenines, therefore they can be considered bioisosteres. The affinity
      data permitted us to ascertain the role and the importance of the N3 in the
      adenine or 8-azaadenine moiety in the receptor binding and to study the dimension
      of the receptor lipophilic pocket which is filled by the N6 substituent of
      adenosine derivatives.

PMID- 14642331
TI  - Synthesis, structural characterization and in vitro antitumor activity of 4
      dimethylaminopyridinium (6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides.
AB  - Previously, we have described a novel series of low molecular weight cancer
      specific antitumor agents with aminium N-(1,1-dioxo-1,4,2-benzodithiazin-3
      yl)arylsulfonamidate structure. In an attempt to determine some of the structural
      features that account for the cytotoxic activity of such aminium salts, a novel
      series of 4-dimethylaminopyridinium (1,1-dioxo-1,4,2-benzodithiazin-3
      yl)methanides (6-19) has been synthesized by the reactions of 3-methylthio-1,4,2
      benzodithiazine1,1-dioxides with 4-DMAP and some active methylene compounds. The
      in vitro antitumor activity of these compounds has been tested in the National
      Cancer Institute (NCI), and relationships between structure and antitumor
      activity are discussed. Among the aminium salts 4-dimethylamino-pyridinium 4
      chlorobenzoyl cyano (6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3
      yl)methanide (9) was superior to other pyridinium salts in terms of both
      remarkable activity (log GI50 and logTGI<-8.00) and high selectivity for the lung
      HOP-92 and melanoma UACC-257 cell lines.

PMID- 14642332
TI  - Synthesis of 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives
      as potential antimicrobial agents.
AB  - In the present study, a series of 1-ethyl/benzyl-6-fluoro-7-(substituted
      piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid were synthesized and
      characterized by IR, 1H-NMR, mass spectral and elemental analysis. The in vitro
      antibacterial and antifungal activities of the compounds were evaluated by paper
      disc diffusion method. The minimum inhibitory concentrations (MIC) of the
      compounds were also determined by agar streak dilution method. The in vivo
      antibacterial activity of the compounds against Escherichia coli was also
      evaluated by mouse protection test. All the compounds exhibited significant
      antibacterial and weak antifungal activities. The in vivo antibacterial activity
      (ED50) against E. coli was 50-160 mg kg(-1) in the order of 7<9<8<10. 1-ethyl-6
      fluoro-7-(2,5-dioxo-piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
      (7) was found to exhibit the most potent in vitro antimicrobial activity with MIC
      of 4.1, 3.1, 3.1, 2.4, 1, 1, 25 and >100 microg mL(-1) against Staphylococcus
      aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, E. coli,
      Klebsiella pneumoniae, Candida albicans and Aspergillus niger.

PMID- 14642333
TI  - Synthesis and biological activities of diflunisal hydrazide-hydrazones.
AB  - Several diflunisal hydrazide-hydrazone derivatives namely 2',4'-difluoro-4
      hydroxybiphenyl-3-carboxylic acid [(5-nitro-2-furyl/substitutedphenyl)methylene]
      hydrazide (3a-o) have been synthesised. Methyl 2',4'-difluoro-4-hydroxybiphenyl-3
      carboxylate (1) and 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide
      (2) were also synthesised and used as intermediate compounds. All synthesised
      compounds were screened for their antimycobacterial activity against
      Mycobacterium tuberculosis H37 Rv, antimicrobial activities against various
      bacteria, fungi and yeast species. Compound 3a have shown activity against
      Staphylococcus epidermis HE-5 and Staphylococcus aureus HE-9 at 18.75 and 37.5
      microg mL(-1), respectively. Compound 3o have exhibited activity against
      Acinetobacter calcoaceticus IO-16 at a concentration of 37.5 microg mL(-1),
      whereas Cefepime, the drug used as standard, have been found less active against
      the microorganisms mentioned above. The synthesised compounds were found to
      provide 12-34% inhibition of mycobacterial growth of M. tuberculosis H37 Rv in
      the primary screen at 6.25 microg mL(-1). Anticonvulsant activity of the
      compounds were also determined by maximal electroshock (MES) and subcutaneous
      metrazole (scMET) tests in mice and rats following the procedures of
      antiepileptic drug development (ADD) program of the National Institutes of Health
      (NIH). Compound 3k showed 25% protection against MES induced seizures in p.o. rat
      screening at a dose level of 30 mg kg(-1) whereas 3n and 3o showed neurotoxicity
      after 4 and 0.5 h at a dose level of 100 and 300 mg kg(-1), respectively.

PMID- 14642334
TI  - Hydrogen bond interactions of a series of N-substituted TXA2 receptor
      antagonists.
AB  - A series of N-substituted sulphonamide based thromboxane A2 (TXA2) receptor
      antagonists were synthesised with the objective to explore the role of hydrogen
      bond donation properties in the binding of these ligands to the TXA2 receptor.
      Pharmacological evaluation of these compounds revealed that the binding affinity
      decreased significantly with the removal of the hydrogen bond donor. This
      indicates that a hydrogen bond donor is important for the binding of these
      antagonists to the TXA2 receptor.

PMID- 14642335
TI  - Synthesis and antineoplastic activity of 2-alkylaminoethyl derivatives of various
      steroidal oximes.
AB  - Various steroidal oxime ether derivatives in androstene and estrane series have
      been synthesized and evaluated for the antineoplastic activity at National Cancer
      Institute, Bethesda, Maryland, USA. O-alkylation of the oximes by various
      alkylaminoethyl halides gave the oxime ether derivatives. The 17alpha
      ethynylandrostene derivatives 29 (DPJ-684), 30 (DPJ-685), 31 (DPJ-686) and
      estrane derivatives 35 (DPJ-531) and 36 (DPJ-532) were among the small percentage
      of compounds, which have been screened by NCI for in vivo hollow fiber assay by
      virtue of their activity against one or more human tumour cell lines in 60 cell
      line in vitro prescreen. The preliminary in vivo reports of hollow fiber assays
      have been referred to the Biological Evaluation Committee for Cancer Drugs for
      considering these compounds for further detailed in vivo testing.

PMID- 14642336
TI  - Synthesis and anti-microbial activities of choline-like quaternary ammonium
      chlorides.
AB  - New choline-like quaternary ammonium chlorides were obtained. The work-up
      procedure of synthesis was quick and efficient. The obtained chlorides showed
      anti-microbial activities. Quaternary ammonium chlorides derivatives of deanol
      esters exhibited strong activity and wide anti-bacterial spectra, similar to the
      activity of benzalkonium chloride. The relationship between chemical structure
      and anti-microbial activity was analyzed by the QSAR method.

PMID- 14642338
TI  - Evaluation of outcomes from deep sternal wound complications.

PMID- 14642340
TI  - Competition and stoichiometry: coexistence of two predators on one prey.
AB  - The competitive exclusion principle (CEP) states that no equilibrium is possible
      if n species exploit fewer than n resources. This principle does not appear to
      hold in nature, where high biodiversity is commonly observed, even in seemingly
      homogenous habitats. Although various mechanisms, such as spatial heterogeneity
      or chaotic fluctuations, have been proposed to explain this coexistence, none of
      them invalidates this principle. Here we evaluate whether principles of
      ecological stoichiometry can contribute to the stable maintenance of biodiverse
      communities. Stoichiometric analysis recognizes that each organism is a mixture
      of multiple chemical elements such as carbon (C), nitrogen (N), and phosphorus
      (P) that are present in various proportions in organisms. We incorporate these
      principles into a standard predator-prey model to analyze competition between two
      predators on one autotrophic prey. The model tracks two essential elements, C and
      P, in each species. We show that a stable equilibrium is possible with two
      predators on this single prey. At this equilibrium both predators can be limited
      by the P content of the prey. The analysis suggests that chemical heterogeneity
      within and among species provides new mechanisms that can support species
      coexistence and that may be important in maintaining biodiversity.

PMID- 14642341
TI  - The evolution of strong reciprocity: cooperation in heterogeneous populations.
AB  - How do human groups maintain a high level of cooperation despite a low level of
      genetic relatedness among group members? We suggest that many humans have a
      predisposition to punish those who violate group-beneficial norms, even when this
      imposes a fitness cost on the punisher. Such altruistic punishment is widely
      observed to sustain high levels of cooperation in behavioral experiments and in
      natural settings. We offer a model of cooperation and punishment that we call
      STRONG RECIPROCITY: where members of a group benefit from mutual adherence to a
      social norm, strong reciprocators obey the norm and punish its violators, even
      though as a result they receive lower payoffs than other group members, such as
      selfish agents who violate the norm and do not punish, and pure cooperators who
      adhere to the norm but free-ride by never punishing. Our agent-based simulations
      show that, under assumptions approximating likely human environments over the
      100000 years prior to the domestication of animals and plants, the proliferation
      of strong reciprocators when initially rare is highly likely, and that
      substantial frequencies of all three behavioral types can be sustained in a
      population. As a result, high levels of cooperation are sustained. Our results do
      not require that group members be related or that group extinctions occur.

PMID- 14642342
TI  - The competitive dynamics of metapopulations subject to the Allee-like effect.
AB  - It is well recognized that individuals of many species can benefit from the
      presence of conspecifics, a concept broadly referred to as the Allee effect. At
      the metapopulation level, there is an analogous but essentially different
      phenomenon called the Allee-like effect that leads to metapopulation extinction
      thresholds at low habitat occupancy. But so far not adequate attention has been
      paid to this phenomenon. In this paper, the Allee-like effect is introduced into
      a metapopulation model of one species and also that of a three-state two-species
      competitive system. Phase plane analysis is used to investigate the dynamics of
      these models. We demonstrate that the Allee-like effect alone could lead to
      multiple stable states in three-state two-species competitive systems at the
      metapopulation level, and the number of stable states decrease as the Allee-like
      effect becomes more severe. Severe Allee-like effects may make coexistence
      impossible and may even lead to the extinction of both species even if their
      initial habitat occupancies are high and suitable habitats are enough. It is
      especially noticeable that depending on their initial conditions one species may
      exclude the other one that subjects to a weaker Allee-like effect than the
      former, while the second species always excludes the first one when both species
      are assumed to be in the absence of the Allee-like effect. We also investigate
      the habitat destructive effect on the Allee-like system mentioned above. Research
      indicates that the existence of the Allee-like effect makes a metapopulation more
      susceptible to habitat destruction. All in all, the Allee-like effect is probably
      a destabilizing factor that, together with habitat destruction, would affect the
      continuous existence of species. These conclusions may have important
      implications for conservation and metacommunity organization.

PMID- 14642343
TI  - Coalescent process with fluctuating population size and its effective size.
AB  - We consider a Wright-Fisher model whose population size is a finite Markov chain.
      We introduce a sequence of two-dimensional discrete time Markov chains whose
      components describe the coalescent process and the fluctuation of population
      size. For the limiting process of the sequence of Markov chains, the relationship
      of the expectation of coalescence time to the harmonic and the arithmetic means
      of population sizes is shown, and the Laplace transform of the distribution of
      coalescence time is calculated. We define the coalescence effective population
      size (cEPS) by the expectation of coalescence time. We show that cEPS is strictly
      larger (resp. smaller) than the harmonic (resp. arithmetic) mean. As the
      population size fluctuates more quickly (resp. slowly), cEPS is closer to the
      harmonic (resp. arithmetic) mean. For the case of a two-valued Markov chain, we
      show the explicit expression of cEPS and its dependency on the sample size.

PMID- 14642344
TI  - Estimating variability in models for recurrent epidemics: assessing the use of
      moment closure techniques.
AB  - The major role played by demographic stochasticity in determining the dynamics
      and persistence of childhood diseases, such as measles, chickenpox and pertussis,
      has long been realized. Techniques which can be used to estimate the magnitude of
      this stochastic effect are of clear importance. In this study, we assess and
      compare the use of two moment closure approximations to estimate the variability
      seen about the average behavior of stochastic models for the recurrent epidemics
      seen in childhood diseases. The performance of the approximations are assessed
      using analytic techniques available for the simplest epidemiological model and
      using numerical simulations in more complex settings. We also present
      epidemiologically important extensions of previous work, considering variability
      in the SEIR model and in situations for which there is seasonal variation in
      disease transmission. Important implications of stochastic effects for the
      dynamics of childhood diseases are highlighted, including serious deficiencies of
      deterministic descriptions of dynamical behavior.

PMID- 14642345
TI  - Analytic solution of Hubbell's model of local community dynamics.
AB  - Recent theoretical approaches to community structure and dynamics reveal that
      many large-scale features of community structure (such as species-rank
      distributions and species-area relations) can be explained by a so-called neutral
      model. Using this approach, species are taken to be equivalent and trophic
      relations are not taken into account explicitly. Here we provide a general
      analytic solution to the local community model of Hubbell's neutral theory of
      biodiversity by recasting it as an urn model, i.e. a Markovian description of
      states and their transitions. Both stationary and time-dependent distributions
      are analysed. The stationary distribution-also called the zero-sum multinomial-is
      given in closed form. An approximate form for the time-dependence is obtained by
      using an expansion of the master equation. The temporal evolution of the
      approximate distribution is shown to be a good representation for the true
      temporal evolution for a large range of parameter values.

PMID- 14642346
TI  - Age-structured population growth rates in constant and variable environments: a
      near equilibrium approach.
AB  - General measures summarizing the shapes of mortality and fecundity schedules are
      proposed. These measures are derived from moments of probability distributions
      related to mortality and fecundity schedules. Like moments, these measures form
      infinite sequences, but the first terms of these sequences are of particular
      value in approximating the long-term growth rate of an age- structured population
      that is growing slowly. Higher order terms are needed for approximating faster
      growing populations. These approximations offer a general nonparametric approach
      to the study of life-history evolution in both constant and variable
      environments. These techniques provide simple quantitative representations of the
      classical findings that, with fixed expected lifetime and net reproductive rate,
      type I mortality and early peak reproduction increase the absolute magnitude of
      the population growth rate, while type III mortality and delayed peak
      reproduction reduce this absolute magnitude.

PMID- 14642347
TI  - On stochastic logistic population growth models with immigration and multiple
      births.
AB  - This paper develops a stochastic logistic population growth model with
      immigration and multiple births. The differential equations for the low-order
      cumulant functions (i.e., mean, variance, and skewness) of the single birth model
      are reviewed, and the corresponding equations for the multiple birth model are
      derived. Accurate approximate solutions for the cumulant functions are obtained
      using moment closure methods for two families of model parameterizations, one for
      badger and the other for fox population growth. For both model families, the
      equilibrium size distribution may be approximated well using the Normal
      approximation, and even more accurately using the saddlepoint approximation. It
      is shown that in comparison with the corresponding single birth model, the
      multiple birth mechanism increases the skewness and the variance of the
      equilibrium distribution, but slightly reduces its mean. Moreover, the type of
      density-dependent population control is shown to influence the sign of the
      skewness and the size of the variance.

PMID- 14642348
TI  - Cultural niche construction and the evolution of small family size.
AB  - A model of cultural niche construction with two culturally transmitted traits is
      examined. The frequency of individuals with a certain general predisposition,
      which is transmitted vertically, plays a role as the cultural background, or the
      cultural niche, of the population. The cultural background determines the rate of
      oblique, relative to vertical, transmission of another cultural trait that
      affects fertility of individuals. It is assumed that individuals with fewer
      offspring are more likely to achieve social roles that influence the succeeding
      generation and are therefore overrepresented as transmitters in the process of
      oblique transmission. Our model suggests that even a slight overrepresentation of
      those with fewer offspring can drive the evolution of small family size, provided
      that the rate of oblique transmission depends strongly on the cultural
      background. In addition, our model may help to explain the time lag between the
      decrease in death rates and the subsequent decrease in birth rates during the
      demographic transition of industrializing societies.

PMID- 14642349
TI  - Mortality rate versus age.
AB  - A theory of the variation of mortality rate with age is presented. It leads to
      the logistic law, which levels off at old ages.

PMID- 14642350
TI  - Induction of a hypermetabolic state in cultured hepatocytes by glucagon and H2O2.
AB  - Stress hormones and pro-inflammatory cytokines are putative signals triggering
      increased energy expenditure or "hypermetabolism" commonly observed in
      inflammatory states. Cytokines also cause the release of reactive oxidants by
      immune cells resident in tissues in vivo. Therefore, we hypothesized that
      oxidative stress plays a role in the induction of hypermetabolism. We examined
      the effect of glucagon (1.0 nM), a catabolic stress hormone, and the oxidant
      H(2)O(2) (1.0 mM) on the metabolism of stable hepatocyte cultures for 4 days.
      Combined H(2)O(2) and glucagon treatment, but not H(2)O(2) or glucagon used
      alone, increased the hepatocyte oxygen uptake rate 25% above control untreated
      cells after a lag-time of 72 h. The same treatment also increased the expression
      of mitochondrial uncoupling protein-2 (UCP2). These effects were significantly
      inhibited by the antioxidant N-acetylcysteine (5mM) and the pentose phosphate
      pathway (PPP) inhibitor dehydroepianderosterone (200 microM). Glucagon alone
      induced urea synthesis and H(2)O(2) alone induced the PPP. These findings show,
      for the first time, that oxidative stress, in combination with glucagon,
      increases metabolic energy expenditure in cultured cells, and that this effect
      may be mediated by UCP-2. Furthermore, the results implicate the PPP in the
      induction of the hypermetabolic response.

PMID- 14642351
TI  - A comparison of the properties of a Bcl-xL variant to the wild-type anti
      apoptosis inhibitor in mammalian cell cultures.
AB  - The overexpression of bcl-2 and its homologues is a widely used strategy to
      inhibit apoptosis in mammalian cell culture systems. In this study, we have
      evaluated the Bcl-2 homologue, Bcl-x(L) and compared its effectiveness to a Bcl
      x(L) mutant lacking most of the non-conserved unstructured loop domain, Bcl
      x(L)Delta (deletion of amino acids 26 through 83). The cell line, Chinese hamster
      ovary (CHO), was genetically modified to express constitutively Bcl-x(L) or the
      Bcl-x(L) variant and subjected to model apoptotic insults including Sindbis virus
      (SV) infection, gradual serum withdrawal, and serum deprivation. When cells were
      engineered to overexpress Bcl-x(L)Delta, cell death due to the SV was inhibited,
      and Bcl-x(L)Delta provided comparable protection to the wild-type Bcl-x(L) even
      though expression levels were much lower for the mutant. Furthermore, the cells
      expressing Bcl-x(L)Delta continued to proliferate following infection while CHO
      bcl-x(L) ceased proliferation immediately following infection. As a result, total
      production of a heterologous protein encoded on the SV was highest in cell lines
      expressing Bcl-x(L)Delta. Cells expressing the variant Bcl-x(L) also continued to
      proliferate and showed increased viable cell numbers following gradual serum
      withdrawal. In contrast, wild-type Bcl-x(L) expressing CHO cells were found to
      arrest growth but maintain viability following serum withdrawal. Interestingly,
      CHO cells expressing Bcl-x(L)Delta were also able to recover and return to rapid
      growth rates much faster than either the wild-type CHO-bcl-x(L) or CHO following
      the replenishment of fresh complete medium containing 10% FBS. Confocal imaging
      of yellow fluorescent protein (YFP) fused to the N terminus of Bcl-x(L) and Bcl
      x(L)Delta indicated dense aggregates of the Bcl-x(L)Delta while the wild-type
      protein was distributed throughout the cell in a manner resembling transmembrane
      localization. As an alternative to complete removal of the loop domain, Bcl-x(L)
      variants were created in which aspartate residues containing potential caspase
      recognition sites within the loop domain of Bcl-x(L) were removed. Cell
      populations expressing various Bcl-x(L)-Asp mutants were exposed to an apoptotic
      spent medium stimulus, and the cells expressing these Bcl-x(L) variants provided
      increased viabilities as compared to cells containing wild-type Bcl-x(L) protein.
      These studies indicate that modification of anti-apoptotic genes can affect
      multiple cellular properties including response to apoptotic stimuli and cell
      growth. This knowledge can be valuable in the design of improved apoptosis
      inhibitors for biotechnology applications.

PMID- 14642352
TI  - Genetic engineering of Escherichia coli for production of tetrahydrobiopterin.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor for various enzymes in
      mammals. In vivo, it is synthesized from GTP via the three-step pathway of GTP
      cyclohydrolase I (GCHI), 6-pyruvoyl-tetrahydropterin synthase (PTPS) and
      sepiapterin reductase (SPR). BH4 is a medicine used to treat atypical
      hyperphenylalaninemia. It is currently synthesized by chemical means, which
      consists of many steps, and requires costly materials and complicated procedures.
      To explore an alternative microbial method for BH4 production, we utilized
      recombinant DNA technology to construct recombinant Escherichia coli (E. coli)
      strains carrying genes expressing GCHI, PTPS and SPR enzymes. These strains
      successfully produced BH4, which was detected as dihydrobiopterin and biopterin,
      oxidation products of BH4. In order to increase BH4 productivity we made further
      improvements. First, to increase the de novo GTP supply, an 8-azaguanine
      resistant mutant was isolated and an additional guaBA operon was introduced.
      Second, to augment the activity of GCHI, the folE gene from E. coli was replaced
      by the mtrA gene from Bacillus subtilis. These modifications provided us with a
      strain showing significantly higher productivity, up to 4.0 g of biopterin/L of
      culture broth. The results suggest the possibility of commercial BH4 production
      by our method.

PMID- 14642353
TI  - Coordinate expression of multiple bacterial carotenoid genes in canola leading to
      altered carotenoid production.
AB  - Carotenoids have drawn much attention recently because of their potentially
      positive benefits to human health as well as their utility in both food and
      animal feed. Previous work in canola (Brassica napus) seed over-expressing the
      bacterial phytoene synthase gene (crtB) demonstrated a change in carotenoid
      content, such that the total levels of carotenoids, including phytoene and
      downstream metabolites like beta-carotene, were elevated 50-fold, with the ratio
      of beta- to alpha-carotene being 2:1. This result raised the possibility that the
      composition of metabolites in this pathway could be modified further in
      conjunction with the increased flux obtained with crtB. Here we report on the
      expression of additional bacterial genes for the enzymes geranylgeranyl
      diphosphate synthase (crtE), phytoene desaturase (crtI) and lycopene cyclase
      (crtY and the plant B. napus lycopene beta-cyclase) engineered in conjunction
      with phytoene synthase (crtB) in transgenic canola seed. Analysis of the
      carotenoid levels by HPLC revealed a 90% decrease in phytoene levels for the
      double construct expressing crtB in conjunction with crtI. The transgenic seed
      from all the double constructs, including the one expressing the bacterial crtB
      and the plant lycopene beta-cyclase showed an increase in the levels of total
      carotenoid similar to that previously observed by expressing crtB alone but
      minimal effects were observed with respect to the ratio of beta- to alpha
      carotene compared to the original construct. However, the beta- to alpha-carotene
      ratio was increased from 2:1 to 3:1 when a triple construct consisting of the
      bacterial phytoene synthase, phytoene desaturase and lycopene cyclase genes were
      expressed together. This result suggests that the bacterial genes may form an
      aggregate complex that allows in vivo activity of all three proteins through
      substrate channeling. This finding should allow further manipulation of the
      carotenoid biosynthetic pathway for downstream products with enhanced agronomic,
      animal feed and human nutritional values.

PMID- 14642354
TI  - The effects of alternate optimal solutions in constraint-based genome-scale
      metabolic models.
AB  - Genome-scale constraint-based models of several organisms have now been
      constructed and are being used for model driven research. A key issue that may
      arise in the use of such models is the existence of alternate optimal solutions
      wherein the same maximal objective (e.g., growth rate) can be achieved through
      different flux distributions. Herein, we investigate the effects that alternate
      optimal solutions may have on the predicted range of flux values calculated using
      currently practiced linear (LP) and quadratic programming (QP) methods. An
      efficient LP-based strategy is described to calculate the range of flux
      variability that can be present in order to achieve optimal as well as suboptimal
      objective states. Sample results are provided for growth predictions of E. coli
      using glucose, acetate, and lactate as carbon substrates. These results
      demonstrate the extent of flux variability to be highly dependent on
      environmental conditions and network composition. In addition we examined the
      impact of alternate optima for growth under gene knockout conditions as
      calculated using QP-based methods. It was observed that calculations using QP
      based methods can show significant variation in growth rate if the flux
      variability among alternate optima is high. The underlying biological
      significance and general source of such flux variability is further investigated
      through the identification of redundancies in the network (equivalent reaction
      sets) that lead to alternate solutions. Collectively, these results illustrate
      the variability inherent in metabolic flux distributions and the possible
      implications of this heterogeneity for constraint-based modeling approaches.
      These methods also provide an efficient and robust method to calculate the range
      of flux distributions that can be derived from quantitative fermentation data.

PMID- 14642355
TI  - Metabolic engineering for microbial production of shikimic acid.
AB  - Shikimic acid is a high valued compound used as a key starting material for the
      synthesis of the neuramidase inhibitor GS4104, which was developed under the name
      Tamiflu for treatment of antiviral infections. An excellent alternative to the
      isolation of shikimic acid from fruits of the Illicium plant is the fermentative
      production by metabolic engineered microorganisms. Fermentative production of
      shikimic acid was most successfully carried out by rational designed Escherichia
      coli strains by blocking the aromatic amino acid pathway after the production of
      shikimic acid. An alternative is to produce shikimic acid as a result of
      dephosphorylation of shikimate-3-phosphate. Engineering the uptake of carbon, the
      regulatory circuits, central metabolism and the common aromatic pathway including
      shikimic acid import that have all been targeted to effect higher productivities
      and lower by-product formation are discussed.

PMID- 14642356
TI  - Review of the role of anticonvulsant prophylaxis following brain injury.
AB  - Anticonvulsants were once routinely used as prophyllaxis for all head injuries.
      There has been a decline in their recent use. The evidence for use of prophylaxis
      is reviewed. Questions postulated will be answered with the best available
      evidence.

PMID- 14642357
TI  - Ergot of rye-the first specific for migraine.
AB  - Over the past decade the various triptan derivatives have been accepted as the
      most effective available agents for relieving migraine attacks. Prior to that,
      for a period of half a century, ergotamine was the only 'specific' available for
      this purpose. In 1918, Stoll had isolated it from the various alkaloids present
      in extracts of the sclerotia of the fungus Claviceps purpurea (ergot), which grow
      on rye and, to a lesser extent, on other grasses. By 1925 ergotamine was
      beginning to be used to treat migraine attacks. However, as ergotamine was
      present in extracts of ergot, which had been used to treat migraine first in
      Italy in 1862, and then by Edward Woakes (1868) in England, and after him by
      Albert Eulenburg in Germany (1883), the drug had actually come into unrecognised
      use for the disorder more than half a century before ergotamine itself was known
      to exist. Unfortunately, because of ergotamine's chemical and pharmacokinetic
      properties, extracts of ergot of rye were incapable of producing consistent
      therapeutic results, so that general acceptance that the first specific substance
      for migraine treatment existed had to wait until pure ergotamine was available
      for administration.

PMID- 14642358
TI  - John William Springthorpe, 1855-1933. Early Australian epileptologist and keeper
      of the flame for neurosciences.

PMID- 14642359
TI  - Anaesthesia for awake craniotomy: a modern approach.

PMID- 14642360
TI  - Dexamethasone in the treatment of subarachnoid hemorrhage revisited: a
      comparative analysis of the effect of the total dose on complications and
      outcome.
AB  - The benefit of dexamethasone in aneurysmal subarachnoid hemorrhage (SAH) is
      unproven. This actual study re-examined the impact on complications and outcome.
      Two hundred and forty-two patient records were analyzed. Dexamethasone had been
      prescribed individually. Group A consisted of patients in WFNS-grade I to III
      that were given at least 12mg/day dexamethasone for at least five days. All other
      patients in WFNS-grade I to III were assigned to group B. Groups C and D resulted
      from WFNS-grades IV and V, subdivided according to dexamethasone medication as
      groups A and B. Hydrocephalus and re-hemorrhage were significantly less frequent
      in group A than B (19% vs. 37%, P=0.011, and 3% vs. 13%, P=0.037, respectively).
      Favorable outcomes (Glasgow Outcome Scale, GOS 4 and 5) were more frequent in
      group A than B (99% vs. 85%; P=0.003). Frequencies of vasospasm and infections
      did not differ. In groups C and D significant differences were demonstrated for
      frequencies of hydrocephalus (C: 16%, D: 57%; P=0.006) and complications other
      than infection (C: 33%, D: 79%; P=0.002). Favorable outcomes were more frequent
      in group C than D (79% vs. 47%; P=0.046). Frequencies of vasospasm and infections
      did not differ.

PMID- 14642361
TI  - Akinetic mutism following stroke.
AB  - This is an appraisal of the varied clinical presentation and the neural substrate
      for akinetic mutism following stroke. The diagnosis is important as akinetic
      mutism is often misdiagnosed as depression, delirium and locked-in-syndrome. This
      is a descriptive study of eight selected patients with akinetic mutism following
      infarction/haemorrhage in different regions of the brain with characteristic
      syndromes. They involved the critical areas namely, the frontal (cingulate gyrus,
      supplementary motor area and dorso-lateral border zone), basal ganglia (caudate,
      putamen), the mesencephalon and thalamus. The disorders of speech and
      communication took different forms. The speech disorder included verbal inertia,
      hypophonia, perseveration, softened and at times slurred. The linguistic
      disturbances were fluent, non-fluent, anomia and transcortical (motor, mixed)
      aphasias. The findings were related to what is known about the neuroanatomic
      location of the lesions and the role of the frontal-subcortical circuitry in
      relation to behaviour. Akinetic mutism could be explained by damage to the
      frontal lobe and or interruption of the complex frontal subcortical circuits.

PMID- 14642362
TI  - A quarter of a century of neurosurgery: the value of a relational database to
      document trends in neurosurgical practice of a tertiary referral hospital.
AB  - OBJECTIVE AND IMPORTANCE: Increasing interest in evidence-based medicine has
      created a demand for accurate and accessible information on activity and trends
      in clinical practice. A database of all neurosurgery admissions at a teaching
      hospital maintained by a scientist has been utilised to examine changes in
      practice and complications from 1977 to 2001. METHODS: A relational database, set
      up in 1982, now contains an unbroken record of all neurosurgical admissions at
      Royal North Shore Hospital (RNSH) since 1976. It supplies information for
      morbidity and mortality meetings, research and administrative purposes. A total
      of 23,766 admissions from 1977 to 2001 were examined. Statistical analysis of
      trends in age, gender, length of stay (LOS), diagnostic mix, surgery rates and
      complications in admissions was based on diagnostic groupings. RESULTS:
      Proportions of vascular admissions rose and of trauma admissions fell. Mean age
      increased significantly for tumour, trauma and spinal patients; geometric mean
      LOS declined significantly for tumour, spine, vascular, cranial nerve and
      peripheral nerve groups. Concurrently, inpatient death rate fell significantly
      for tumour and vascular patients. Deep vein thrombosis (DVT) rose significantly
      for trauma, vascular, tumour, spinal and infection patients; pulmonary embolism
      (PE) rose significantly for tumour, trauma and spinal patients. There was no
      significant change in wound infection rate at approximately 3.5% of all operated
      patients. Wound haematoma rates fell significantly from 4.0% to 2.9% while the
      rate of postoperative cerebrospinal fluid (CSF) leak rose significantly from 0.5%
      to 2.0% of all operated patients. CONCLUSION: The value of the database is
      demonstrated by its ability to provide analysis which shows statistically
      significant changes over time. Declining death rate and LOS indicate improved
      efficiency in managing patients, but these are offset by rising rates of CSF
      leak, DVT and PE. Such rises reflect the changing patterns of casemix and surgery
      performed, and increasing financial pressures on hospital departments.

PMID- 14642363
TI  - PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination
      in patients with glioblastoma.
AB  - Dissemination of glioblastomas is often observed, but the underlying mechanism is
      not well clarified especially from the genetic viewpoints. The present study
      examined whether PTEN gene mutations and MIB-1 labeling index (LI) correlate with
      the dissemination in 39 consecutive patients with glioblastomas. Dissemination
      was defined as leptomenigeal enhancement by magnetic resonance imaging performed
      in all patients every 2-3 months. We examined PTEN mutations in 26 patients using
      cDNA-based direct sequencing and MIB-1 LI in 38 patients. Median survival time of
      the 39 patients was 16.2 months. Dissemination was found in 17 of 39 patients
      (43.6%). PTEN mutation was significantly associated with dissemination
      (P=0.0140), and higher MIB-1 LI (> or =35%) resulted in earlier dissemination
      (P=0.0156). Kaplan-Meier survival plots showed a significantly poorer survival
      for patients with PTEN mutation (P=0.0012). The results indicate that the
      evaluation of PTEN mutation and MIB-1 LI are useful to predict dissemination and
      prognosis of glioblastomas.

PMID- 14642364
TI  - Cerebellopointine angle medulloblastoma.
AB  - Cerebellopontine angle (CPA) medulloblastoma is a rare tumour. To date, only 19
      cases have been reported over a period of 8 years, we have treated 14 cases of
      CPA medulloblastomas. This is first and the largest series of CPA
      medulloblastomas reported in the world literature.

PMID- 14642365
TI  - Stable ratio of ipsilateral to contralateral sensory motor cortex activity
      despite varying effort and peripheral nerve block.
AB  - BACKGROUND: Ipsilateral sensory motor cortex (SMC) activation can occur during
      hand movements following cerebral injury. We studied the effect of increasing
      task difficulty and temporary peripheral paralysis on patterns of motor system
      activation. METHODS: Six healthy subjects completed a functional MRI paradigm of
      right finger abduction with four stages; light resistance, strong resistance,
      imagined movement and attempted abduction after ulnar nerve blockade. Activation
      maps compared images acquired during rest and task, while region of interest
      analysis measured numbers of activated pixels. RESULTS: All subjects showed some
      ipsilateral SMC activation. Across all subjects and all tasks involving hand
      movement, contralateral activation was proportional to ipsilateral activation
      (2.1:1; r=0.86). CONCLUSIONS: The relationship between ipsilateral and
      contralateral SMC activation remained stable despite differing effort or hand
      paralysis. The contralateral and ipsilateral SMC appear to act in a coordinated
      fashion during unilateral hand movements.

PMID- 14642366
TI  - Interstitial glycerol increase in microdialysis after glycerol enema.
AB  - Microdialysis allows the measurement of extracellular concentrations of various
      endogenous substances, such as excitotoxic amino acids or metabolic end products.
      Recent advances in microdialysis techniques have led to widespread use in
      patients with brain disorders. Microdialysis has proved to be a useful tool for
      monitoring cerebral biochemical metabolism and secondary brain damage in severe
      head injury, subarachnoid haemorrhage, stroke, and epilepsy. In our neurosurgical
      intensive care unit, microdialysis was performed on 42 patients. Four patients
      received a glycerol enema for therapy of a paralytic ileus. A glycerol peak was
      observed in both intracerebral and subcutaneous microdialysis occurring three to
      four hours after the glycerol enema in all four patients. The highest glycerol
      value was 1187micromol/l cerebral and 2997micromol/l in the subcutaneous tissue.
      Our study indicates that besides the measurement of serum osmolality and serum
      glycerol level, microdialysis may be an additional valuable tool to control
      glycerol therapy in patients with cerebral oedema and elevated intracranial
      pressure.

PMID- 14642367
TI  - The importance of the journal club for neurosurgical trainees.
AB  - The enormous volume of published literature in the field of neurosurgery
      represents an impossible task for the trainee or consultant neurosurgeon to
      digest. The aim of this paper is to review the views of current accredited
      trainees as to how best achieve the goals of information acquisition in
      combination with a heavy clinical workload. The views of 22 accredited trainees
      in the field of neurosurgery in Australia and New Zealand are reviewed. The
      recommendations from this study are that journal clubs are paramount to
      neurosurgical training for acquisition of new information, the frequency of
      meetings should be monthly and papers discussed should be those that impact
      significantly on management and standard of care and be founded on evidence-based
      medicine criteria.

PMID- 14642368
TI  - Images in neuroscience. Devic's disease.

PMID- 14642369
TI  - Evaluation of the behaviour of a thermal diffusion sensor in a high field
      strength magnetic resonance system: an experimental study.
AB  - Patients with acute brain pathology requiring ferromagnetic bio-medical implants
      for on-going invasive monitoring are largely excluded from the benefits of MRI
      scanning. We evaluated the behaviour of a thermal diffusion cortical blood flow
      (TD-CBF) sensor both in vitro (phantom gelatin model) and in vivo environments in
      a high field strength MRI system. Two baboons underwent cranial subdural
      implantation of 2 TD-CBF sensors/hemisphere and a single left parietal sensor was
      implanted subcortically to determine any deleterious effects. Using standard MRI
      sequences, artefact size, thermal effects, current generation, movement and
      reliability of recordings were assessed during scanning. The deflection forces
      were negligible, no observable thermal effects were demonstrated, while wide
      fluctuations in cerebral blood flow recordings were recorded. Mean image artefact
      size for implanted sensors was 6 times larger than in vitro. Patients with an
      implanted TD-CBF sensor may be safely imaged provided the device is disconnected.
      The MRI images obtained are of an acceptable quality.

PMID- 14642370
TI  - Carcinoid associated encephalitis successfully treated with tryptophan.
AB  - This case report describes the rare phenomenon of encephalopathy associated with
      massive carcinoid tumor. Extensive investigation failed to reveal an obvious
      cause but a presumptive diagnosis of tryptophan deficiency was made and she was
      commenced on tryptophan dietary supplements. A rapid and complete response
      resulted. This case report discusses this unusual case and reviews the literature
      regarding carcinoid associated encephalopathy.

PMID- 14642371
TI  - Ligamentum flavum cyst.
AB  - INTRODUCTION: Although magnetic resonance imaging (MRI) of ligamentum flavum and
      other spinal cysts have been well described, the role of contrast enhancement in
      this diagnosis has been neglected. We describe such a case and correlate the MRI
      findings with the histopathology. CASE REPORT: A 71-years-old woman was admitted
      with of neurogenic lumbar claudication. X-rays of the lumbar spine showed
      degenerative changes with scoliosis. Lumbar magnetic resonance imaging
      demonstrated a L3/4 extradural cystic mass. An L3 laminectomy was performed and
      the mass excised. The histopathological diagnosis was consistent with a
      ligamentum flavum cyst. Postoperatively, the patient's symptoms resolved
      completely. CONCLUSION: The possibility of a ligamentum flavum cyst should be
      considered whenever a hyperintense extradural mass with a peripheral hypointense
      rim on T2 weighted and slightly contrast enhanced peripheral rim on T1 weighted
      MRI is identified in a patient with degenerative changes of the lumbar spine.

PMID- 14642372
TI  - Pitch perception abnormality as a side effect of carbamazepine.
AB  - Carbamazepine (CBZ) is frequently used to treat patients with epilepsy,
      neuralgia, psychiatric diseases, etc. We prescribe it with care due to its side
      effects, mainly such as dizziness, sleepiness and cerebellar symptoms. But pitch
      perception abnormality is an uncommon side effect. We describe the case of a 12
      year-old girl who exhibited half tone lowered pitch perception abnormality caused
      by CBZ. As CBZ acts as a central nervous system (CNS) inhibitor, we speculate
      that CBZ inhibits CNS and patients misperceive notes. We must prescribe CBZ with
      care to prevent pitch perception abnormalities.

PMID- 14642373
TI  - Treatments of multi-invasive giant prolactinoma.
AB  - We present a 68-year-old male patient with an exceptionally aggressive tumour
      which invaded to the skull base, cavernous sinus, nasopharynx, sphenoid sinus,
      pituitary fossa, bilateral parasellar regions, premedullary cistern, and left
      infratemporal fossa. Headache was the only symptom. The serum prolactin level was
      95,973 ng/ml. The patient was treated by right subfrontal craniotomy with removal
      of the tumour. Because it did not respond well to surgical treatment and the
      electron micrograph showed abundant secretory granules in some parts of the
      specimen, post-operative radiotherapy and bromocriptine therapy were instituted.
      After combined therapies and a long-term follow-up, only little residual
      pituitary tumour was seen with serum prolactin progressively dropped to 717 ng/ml
      with no obvious symptoms. The histological findings, the ideal treatments and the
      clinical course of multi-invasive giant prolactinoma will be discussed.

PMID- 14642374
TI  - Gross total surgical removal of malignant glioma from the medulla oblongata:
      report of two adult cases with reference to surgical anatomy.
AB  - Surgery was performed on the medulla oblongata of two adult patients with
      malignant glioma. Gross total resection of the tumors, located laterally or
      medially in the upper half of the medulla respectively, was achieved. The patient
      with the medially located tumor experienced significant postoperative
      neurological deterioration including sleep apnea. The other patient with the
      laterally located tumor showed symptomatic improvement without respiratory
      complications. The patient with an anaplastic astrocytoma survived approximately
      4 years and the patient with a glioblastoma multiforme approximately 2 years.
      Although the upper half of the medulla is more critical than the lower half, a
      lateral approach to the upper half of the medulla appears to be relatively safer
      than a medial approach. Some cases of focal malignant gliomas in the medulla may
      be amenable to gross total resection in order to achieve improved outcome.
      Surgery can be undertaken when a tumor is unilateral and its margin appears
      relatively clear on magnetic resonance images.

PMID- 14642375
TI  - Identical cerebral aneurysms in siblings: report of two families.
AB  - Two pairs of sisters with identical cerebral aneurysms are reported. In the first
      family, a sibship of three, the two female members presented with subarachnoid
      haemorrhages from identical, left internal carotid artery bifurcation aneurysms.
      The subarachnoid haemorrhage occurred in one of the sisters at the age of 20 and
      at the age of 50 in the other. The remaining healthy sibling, a 40-year-old male,
      underwent elective cerebral angiography, which was normal. The other sibship, two
      48-year-old female identical twins, had identical right middle cerebral artery
      aneurysms. The first twin became symptomatic after subarachnoid haemorrhage. The
      aneurysm in her identical twin was identified by screening angiography. There
      were no verified subarachnoid haemorrhages among the parents and grandparents in
      either family. No systemic anomalies were identified and collagen type 3
      deficiencies were excluded. The identical location of these familial aneurysms,
      particularly in view of the relatively rare location in the first family,
      suggests that local factors in the developing vascular tree may play a role in
      the pathogenesis of saccular aneurysms in addition to systemic anomalies
      affecting the general structure of cerebral vascular walls.

PMID- 14642376
TI  - Improvement of generalised dystonia by olanzapine treatment.
AB  - This is the first report on generalised dystonia beneficially treated by
      olanzapine. A 63-year-old Taiwanese man with intractable general dystonia was
      treated with olanzapine starting at a dose of 2.5 mg/day to the maximal dose of
      15 mg/day. Clinically, there was slow, but steady, improvement in his dystonia
      and disability after olanzapine treatment. Evaluation of his dystonia 3 months
      later revealed 70% improvement on dystonic movement and 60% on disability on the
      Burke-Fahn-Marsden Dystonia Scale. The result suggests that treatment with
      olanzapine can be an alternative therapy for patients with generalised dystonia.

PMID- 14642377
TI  - A distal anterior cerebral artery aneurysm in infant: disappearance and
      reappearance of the aneurysm.
AB  - The incidence of intracranial aneurysms in childhood is rare, especially in
      infancy. Spontaneous thrombosis of a cerebral aneurysm in a child is very rare,
      particularly in a non-giant aneurysm. We report a case of a 1-month-old girl with
      a distal anterior cerebral artery aneurysm which disappeared spontaneously after
      subarachnoid hemorrhage and reappeared 6 months later. Surgical resection of the
      aneurysm was performed and she discharged uneventfully 10 days later.
      Histological examination revealed an aneurysm with a fibrous muscular layer,
      absence of the internal elastic lamina and partial hypertrophy of the intimal
      layer. Though the pathogenesis of this aneurysm is uncertain, two hypotheses are
      discussed.

PMID- 14642378
TI  - Single choroid plexus metastasis 16 years after nephrectomy for renal cell
      carcinoma: case report and review of the literature.

PMID- 14642379
TI  - Intracranial epithelioid schwannoma - a case report.
AB  - We report a case of an intracranial epithelioid schwannoma. Epithelioid
      schwannoma is a low-grade malignant peripheral nerve sheath tumor that occurs
      most commonly in the limbs and inguinal region. Association with cranial nerves
      has been reported to be rare and in almost all cases has only involved
      extracranial distal branches.

PMID- 14642380
TI  - Surgery improves vision and cosmetic appearance of an adult patient with fibrous
      dysplasia of the frontal bone.
AB  - A 31-year-old woman with fibrous dysplasia (FD) of the left forehead was
      reported. Visual acuity impairment and diplopia were slowly progressive for 6
      months associated with marked protrusion of her left forehead. Removal of left
      forehead lesion including the orbital ridge and total decompression of the optic
      canal and superior orbital fissure improved these visual symptoms dramatically.
      Reconstructive cranioplasty using artificial bone made by hydroxyapatite
      (Apaceram) was very satisfactory in cosmetic appearance. Surgical indication and
      neuroradiological findings of cranial FD are discussed as well as a review of the
      literatures.

PMID- 14642382
TI  - Gene expression profile of oxidant stress and neurodegeneration in transgenic
      mice deficient in alpha-tocopherol transfer protein.
AB  - Alpha-tocopherol transfer protein (TTP) regulates the retention and secretion of
      alpha-tocopherol (alpha-T) by the liver. Deletion of the TTP gene (Ttpa) in mice
      results in systemic deficiency of alpha-T and neurological dysfunctions described
      in patients with mutated Ttpa. We have explored genome-wide changes in mRNAs from
      brain cortex and liver of Ttpa-deficient (Ttpa(-/-)) mice and wild-type
      (Ttpa(+/+)) mice. Selective inductions of genes regulated by antioxidant response
      elements were detected in Ttpa(-/-) livers compared to Ttpa(+/+) livers,
      suggesting increased oxidant stress in Ttpa(-/-) livers. The activation of cell
      proliferation pathways in Ttpa(-/-) livers was indicated by the induction of
      genes that encode growth factor-binding proteins, mitogen-activated protein
      kinase kinase 3, and apoptosis inhibitor 6. The induction of synuclein-alpha and
      repression of synuclein-beta genes was detected in Ttpa(-/-) cortex. This may
      predispose Ttpa(-/-) cortex to increased formation of synuclein-alpha aggregates
      and Lewy body, often associated with oxidant stress. Cortex of Ttpa(-/-) mice
      revealed repression of genes encoding synaptic proteins, protein kinase C family
      members, and myelin proteins. A 13-fold decrease in the expression of retinoic
      acid receptor-related orphan receptor-alpha mRNA predicts staggerer-like
      phenotype (ataxia and deficits of motor coordination) of Ttpa(-/-) mice. The
      repression of specific genes that determine synaptic plasticity and neuronal
      development may account for suppressed electrophysiological activities of cortex
      and impaired behavior in Ttpa(-/-) mice.

PMID- 14642383
TI  - Cellular responses to H(2)O(2) and bleomycin-induced oxidative stress in L6C5 rat
      myoblasts.
AB  - In muscle cells, reactive oxygen species (ROS) are continually generated. It is
      believed that these molecules have a well-established role as physiological
      modulators of skeletal muscle functions, ranging from development to metabolism
      and from blood flow to contractile functions. Moreover, ROS may contribute to the
      development of muscle fatigue, inflammation, and degeneration, and may be
      implicated in many muscle diseases. The aim of the present study was to verify
      the role of short or prolonged exposure to oxidative stress, generated by
      different concentrations of H(2)O(2), on growth, chromosomal aberrations, and
      apoptosis induced in cultured L6C5 rat muscle cells used as model for myoblasts.
      Our results indicate that, in L6C5 cells, reactive oxygen intermediates (ROI) can
      activate distinct cell pathways leading to cell growth induction and development
      of resistant phenotype, or to chromosomal aberrations, cell cycle arrest, or cell
      death. The positive vs. negative effects of H(2)O(2)-altered redox potential in
      myoblasts are strictly related to the intensity of oxidative stress, likely
      depending on the types and number of cellular targets involved. Among these, DNA
      molecules appear to be very sensitive to breakage by H(2)O(2), although DNA
      damage is not directly responsible for ROI-induced apoptosis in L6C5 rat
      myoblasts.

PMID- 14642384
TI  - An improved HPLC measurement for GSH and GSSG in human blood.
AB  - The pathophysiological sequelae of oxidative/nitrosative stress are notoriously
      difficult to quantify. Despite these impediments, the medical significance of
      oxidative/nitrosative stress has become increasingly recognized to the point that
      it is now considered to be a component of virtually every disease. The level of
      oxidative stress can be quantified in blood by the measurement of the increase in
      glutathione disulfide (GSSG) and the decrease in the GSH/GSSG ratio, which has
      been shown to be altered in a variety of human diseases such as lung
      inflammation, amyotrophic lateral sclerosis, chronic renal failure, malignant
      disorders, and diabetes. Among the proposed methods for GSH/GSSG detection, the
      amino group derivatization with 2,4-dinitrofluorobenzene followed by HPLC
      separation has the advantage of allowing evaluation of both parameters within a
      single run contemporaneously. However, it has been shown that the application of
      this method on blood samples is not reproducible. In this report, we offer an
      explanation for these experimental limits and suggest some modifications that
      allow the application of this method to blood samples. The modified method has a
      low detection limit (0.5 microM, i.e., 1.4 pmoles) and a high reproducibility
      with a within-run imprecision of less than 2%. It could have a wide application
      as it is simple, virtually artifact-free, and not time-consuming, especially for
      large-scale screening studies.

PMID- 14642385
TI  - Nitric oxide promotes strong cytotoxicity of phenolic compounds against
      Escherichia coli: the influence of antioxidant defenses.
AB  - The induction of mutagenic and cytotoxic effects by simple phenolics, including
      catechol (CAT), 3,4-dihydroxyphenylacetic acid (DOPAC), hydroquinone (HQ), and
      2,5-dihydroxyphenylacetic (homogentisic) acid (HGA), appears to occur through an
      oxidative mechanism based on the ability of these compounds to undergo
      autoxidation, leading to quinone formation with the production of reactive oxygen
      species. This is supported by the detection of such adverse effects in plate
      assays using Escherichia coli tester strains deficient in the OxyR function, but
      not in OxyR(+) strains. The OxyR protein is a redox-sensitive regulator of genes
      encoding antioxidant enzymes including catalase and alkyl hydroperoxide
      reductase, which would eliminate hydrogen peroxide. Methyl-substituted phenolics
      such as 4-methylcatechol (MCAT) and methylhydroquinone (MHQ) produced, in
      addition to oxidative toxicity, marked cytotoxic effects against OxyR(+) cells,
      thus revealing a mechanism of toxicity not mediated by hydrogen peroxide that
      could involve quinones and quinone methides arising from MCAT and MHQ oxidation.
      Quinone compounds could also be responsible for the enhanced cytotoxicity of
      certain phenolics when combined with a nitric oxide (NO(*)) donor such as
      diethylamine/NO (DEA/NO). Phenolics scavenge NO(*) and, in turn, NO(*) oxidizes
      phenolics to form their quinone derivatives. In OxyR(+) cells, where the
      oxidative toxicity is inhibited, DEA/NO promoted exceptional increases in the
      cytotoxicity of CAT and 3,4-dihydroxycinnamic (caffeic) acid (CAF), which both
      exhibited very low oxidative cytotoxicity, as well as in that of MCAT, HQ, and
      MHQ. In contrast, DEA/NO failed to promote toxicity by DOPAC and HGA, probably
      due to their ability to undergo oxidative polymerization, leading to the
      formation of melanins. Spectroscopic studies demonstrated quinone generation from
      the oxidation of CAF, HQ, and MHQ by DEA/NO. The o-quinone derived from CAF was
      rather unstable and decomposed during its isolation. For the generation of toxic
      quinones, e.g., to be used as therapeutic agents producing antitumor or
      antibacterial effects, the isolation step could be avoided with the method
      proposed. It combines quinone precursors, i.e. phenolic compounds, with an
      oxidant such as NO(*).

PMID- 14642386
TI  - In situ detection and localization of lipid peroxidation in individual bovine
      sperm cells.
AB  - Reactive oxygen species (ROS) have been implicated in many pathologies, including
      sub- and infertility. Freeze/thawing of sperm samples is routinely performed in
      the cattle breeding industries in order to perform artificial insemination. This
      freeze/thaw procedure is known to induce ROS in sperm samples. Lipid peroxidation
      in fresh and frozen/thawed sperm cells was assessed by mass spectrometric
      analysis of the main endogenous phospholipid class, phosphatidylcholine, and by
      fluorescence techniques using the lipid peroxidation reporter probe C11
      BODIPY(581/591). Peroxidation as reported by the fluorescent probe, clearly
      corresponded with the presence of hydroxy- and hydroperoxyphosphatidylcholine in
      the sperm membranes, which are early stage products of lipid peroxidation. This
      allowed us, for the first time, to correlate endogenous lipid peroxidation with
      localization of this process in living sperm cells. Lipid peroxidation was
      particularly strong in the midpiece and tail of frozen/thawed spermatozoa and
      significantly less intense in the head. Induction of peroxidation in fresh sperm
      cells with the lipid soluble ROS tert-butylhydroperoxide gave an even more
      pronounced effect, demonstrating antioxidant activity in the head of fresh sperm
      cells. Furthermore, we were able to show that spontaneous peroxidation was not a
      result of cell death, as only a pronounced subpopulation of living cells showed
      peroxidation after freeze/thawing.

PMID- 14642387
TI  - Antioxidant activity of a Schiff base of pyridoxal and aminoguanidine.
AB  - We recently reported that PL-AG, a Schiff base of pyridoxal and aminoguanidine,
      was more effective than aminoguanidine (AG), a well-known anti-diabetic
      complication compound, in preventing nephropathy in diabetic mice and presented
      brief data indicating the antioxidant activity of the adduct. In the present
      study, we additionally investigated the inhibitory activity of PL-AG in
      comparison with that of AG against in vitro and in vivo oxidation. PL-AG was more
      potent than AG and reference compounds such as pyridoxal and pyridoxamine in any
      of the five antioxidant activities examined in vitro, i.e., hydrogen peroxide
      scavenging, hydroxyl radical-scavenging, superoxide radical-scavenging, ascorbic
      acid-autoxidation inhibitory, and low-density lipoprotein (LDL)-oxidation
      inhibitory activities, the last two of which were assessed in the presence of
      Cu(2+). Unlike AG, PL-AG did not show the pro-oxidant activity. The inhibitory
      activity of PL-AG against lipid peroxidation in diabetic rats was higher than
      that of AG, for example, the amounts of malondialdehyde in erythrocytes (nmol/g
      hemoglobin; mean +/- SD) in normal, untreated diabetic, AG-treated diabetic, and
      PL-AG-treated diabetic rats were 3.53 +/- 0.35, 4.99 +/- 0.23, 4.65 +/- 0.45, and
      4.06 +/- 0.35, respectively. A fluorescent substance different from PL-AG was
      found in the plasma and urine of rats treated with PL-AG. The chemical structure
      of this substance, i.e., oxidized PL-AG, was determined by a combination of
      nuclear magnetic resonance, mass, and infrared spectrometry. AG dramatically
      decreased the pyridoxal phosphate level in the diabetic rat liver, whereas PL-AG
      only moderately affected it. Our results indicate that the antioxidant activity
      of PL-AG is due to its chelation with transition metal ions and to scavenging of
      reactive oxygen species. They also suggest that PL-AG is more promising for the
      treatment of diabetic complications than AG.

PMID- 14642388
TI  - Red blood cells upregulate cytoprotective proteins and the labile iron pool in
      dividing human T cells despite a reduction in oxidative stress.
AB  - We have recently reported that red blood cells (RBC) promote T cell growth and
      survival by inhibiting activation-induced T cell death. In the present study, we
      have examined parameters of oxidative stress and intracellular iron in activated
      T cells and correlated these data with the expression of ferritin, heme oxygenase
      1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of
      RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified
      proteins, suggesting that RBC efficiently counteracted ROS production on the
      activated T cells. Flow cytometry and immunodetection demonstrated that T cells
      dividing in the presence of RBC had increased levels of intracellular ferritin
      rich in L-subunits and HO-1 along with a downmodulation in CD71 expression.
      Finally, using the fluorescent iron indicator calcein and flow cytometry
      analysis, we were able to show that a relative amount of the labile iron pool
      (LIP) was upregulated in T cells growing in the presence of RBC. These findings
      are consistent with a typical response to iron overload. However, neither heme
      compounds nor ferric iron reproduced the levels of expansion and survival of T
      cells induced by intact RBC. Altogether, these data suggest that RBC inhibit
      apoptosis of activated T cells by a combination of ROS scavenging and
      upregulation of cytoprotective proteins such as ferritin and HO-1, which may
      counteract a possible toxic effect of the increased intracellular free iron.

PMID- 14642389
TI  - Neutrophil myeloperoxidase chlorinates and nitrates soy isoflavones and enhances
      their antioxidant properties.
AB  - Soy isoflavones and other polyphenolics have a number of potentially important
      beneficial effects on the pro-oxidant aspects of chronic inflammation. The impact
      of inflammatory cell-specific metabolism of polyphenolics, which can include
      halogenation and nitration, on the properties of these compounds has not been
      examined. Using either human neutrophils or differentiated human leukemia cells
      (HL-60) stimulated with phorbol ester to elicit a respiratory burst, the
      hypothesis that local generation of reactive oxygen and nitrogen species may
      metabolize and modify the biological properties of the soy isoflavones was
      examined. Coincubation of the stimulated cells with genistein or daidzein had no
      effect on the respiratory burst. Medium from stimulated cells in the presence of
      the isoflavones and NO(2)(-) increased the inhibition of copper-induced LDL
      oxidation. Mass spectrometry analysis of this medium revealed that
      monochlorinated, dichlorinated, and nitrated isoflavones, formed through a
      myeloperoxidase-dependent mechanism, were present. The consumption of genistein
      in the presence of cells was both extensive and rapid with > 95% of the genistein
      converted to either the chlorinated or nitrated metabolites within 30 min.
      Chemically synthesized 3'-chlorogenistein and 3'-chlorodaidzein increased the
      inhibition of LDL oxidation by approximately 4-fold and 2-fold over genistein and
      daidzein, respectively. These results lead to the hypothesis that inflammatory
      cell-specific metabolism of polyphenolics can modify the properties of these
      compounds at the local site of inflammation.

PMID- 14642390
TI  - Inhibition of poly(ADP-RIBOSE) polymerase (PARP) by nitric oxide and reactive
      nitrogen oxide species.
AB  - The poly(ADP-ribose) polymerase (PARP) family of nuclear enzymes is involved in
      the detection and signaling of single strand breaks induced either directly by
      ionizing radiation or indirectly by the sequential action of various DNA repair
      proteins. Therefore, PARP plays an important role in maintaining genome
      stability. Because PARP proteins contain two zinc finger motifs, these enzymes
      can be targets for reactive nitrogen oxide intermediates (RNOS) generated as a
      result of nitric oxide (NO) biosynthesis in an aerobic environment. The effects
      of RNOS on the activity of purified PARP were examined using donor compounds.
      Both NO and nitroxyl (HNO) donors were found to be inhibitory in a similar time
      and concentration manner, indicating that PARP activity can be modified under
      both nitrosative and oxidative conditions. Moreover, these RNOS donors elicited
      comparable PARP inhibition in Sf21 insect cell extract and intact human MCF-7
      cancer cells. The concentrations of donor required for 90% inhibition of PARP
      activity produce RNOS at a similar magnitude to those generated in the cellular
      microenvironment of activated leukocytes, suggesting that cellular scavenging of
      RNOS may not be protective against PARP modification and that inhibition of PARP
      may be significant under inflammatory conditions.

PMID- 14642391
TI  - Ascorbic acid recycling in human erythrocytes is induced by smoking in vivo.
AB  - Tobacco smoke contains large numbers of radicals that burden the antioxidant
      defense and, thus, lower plasma antioxidants, in particular vitamin C or ascorbic
      acid, is commonly observed among smokers. Ascorbic acid recycling describes the
      process in which ascorbic acid is oxidized to dehydroascorbic acid by various
      pathways and subsequently reduced back to ascorbic acid intracellularly, e.g., in
      erythrocytes, thereby preserving the ascorbic acid pool. In humans who are unable
      to synthesize ascorbic acid, and in smokers in particular, who are prone to
      oxidation, this process must be very efficient and of great importance. It has
      previously been reported that isolated erythrocytes subjected to tobacco smoke in
      vitro had significantly lower ascorbic acid recycling as compared to controls. In
      contrast to these findings, we now report that freshly isolated erythrocytes from
      long-term smokers (n = 39) display a significantly increased rate of ascorbic
      acid recycling in vivo as compared to those isolated from nonsmokers (n = 31; p
      <.0001). Preliminary data suggests that the increase results from induction of
      dehydroascorbic acid reductase activity rather than from differences in energy
      status, glutathione content, or altered transport capacity. The induction of
      ascorbic acid recycling as a potential adaptation mechanism of the antioxidant
      defense to oxidative insults is discussed.

PMID- 14642392
TI  - Effect of cigarette smoke on oral peroxidase activity in human saliva: role of
      hydrogen cyanide.
AB  - Peroxidase activity in human saliva is composed of salivary peroxidase (80%), of
      salivary glandular origin, and myeloperoxidase (20%), of leukocyte origin. The
      term oral peroxidase (OPO) is used here to denote the total activity of both
      peroxidase species. Using the 2-nitrobenzoic acid-thiocyanate assay, OPO activity
      was measured in the saliva of nonsmokers after exposure to gas-phase cigarette
      smoke (CS) in an in vitro system using three puffs of CS in 1 h. A marked
      decrease of 76% of activity was observed following three puffs of CS. In order to
      elucidate the mechanism by which CS caused loss of OPO activity, several oxidants
      and antioxidants were applied to saliva in vitro in the presence and absence of
      CS. No protection for CS-induced loss of OPO activity occurred in the presence of
      glutathione, N-acetylcysteine, ascorbic acid, or Desferal. Exposure of saliva to
      purified aldehydes present in CS did not significantly affect OPO loss of
      activity. Similarly, ascorbic acid in the presence of FeCl(3) and nicotine also
      had no effect on OPO activity. Exposure of OPO to cyanate at levels present in CS
      caused a 65-70% loss of OPO activity, which was reversible after 24 h of
      dialysis. Moreover, hydroxocobalamin, a known cyanate chelator, could prevent CS-
      and potassium cyanide-induced inactivation of OPO by 70-90%. The results show
      that hydrogen cyanide, known to be present in microgram amounts per cigarette, is
      likely to be the species in CS responsible for loss of salivary OPO activity. The
      finding of reduced salivary OPO levels after CS exposure may represent a
      contributory mechanism for CS-related compromises in antimicrobial defenses in
      the aerodigestive tract.

PMID- 14642393
TI  - Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels.
AB  - Preeclampsia is a common ( approximately 7% of all pregnancies) disorder of human
      pregnancy in which the normal hemodynamic response to pregnancy is compromised.
      Despite many years of intensive research, the pathogenesis of preeclampsia is
      still not fully understood. The objective of the present study was to investigate
      the concentration of coenzyme Q10 in normal pregnancy and preeclampsia. Pregnant
      women (n = 18), women with preeclampsia (n = 12), and nonpregnant normotensive
      women (n = 22) were included. Plasma levels of coenzyme Q10 were measured by high
      performance liquid chromatography. Plasma coenzyme Q10 levels were significantly
      higher in normal pregnant women (mean = 1.08, SEM = 0.08 umol/l; p <.005) in
      comparison to nonpregnant women (mean = 0.86, SEM = 0.16 umol/l) and women with
      preeclampsia (mean = 0.7, SEM = 0.03 umol/l; p <.0001). These results
      demonstrated that during preeclampsia there is a significant decrease in plasma
      levels of coenzyme Q10 compared to normal pregnant women, and compared to those
      who are not pregnant.

PMID- 14642394
TI  - Nitric oxide induces apoptosis via hydrogen peroxide, but necrosis via energy and
      thiol depletion.
AB  - We investigated the mechanisms by which two nitric oxide (NO) donors,
      diethylenetriamine/NO adduct (DETA/NO) and S-nitrosoglutathione (GSNO), induced
      cell death in a J774 macrophage cell line. Both NO donors induced caspase
      activation within 6 h, but only DETA/NO-induced caspase activation was sensitive
      to inhibition of p38 and was completely prevented by antioxidants catalase,
      ascorbate, dehydroascorbate, or N-acetylcysteine, suggesting that DETA/NO-induced
      apoptosis may be mediated by H(2)O(2). Consistent with this, DETA/NO acutely
      stimulated reactive oxygen species (ROS) production by mitochondria and cells,
      and inhibited catalase-mediated H(2)O(2) breakdown in cells. After prolonged, 24
      h exposure of cells to DETA/NO, inactivation of caspases occurred, which was
      accompanied by an increase in necrosis. DETA/NO-induced necrosis was insensitive
      to caspase inhibitors, but was partially prevented by catalase or N
      acetylcysteine, and was preceded by inhibition of glyceraldehyde-3-phosphate
      dehydrogenase and a decrease in cellular adenosine triphosphate (ATP). GSNO was
      even more potent in inhibiting glycolysis and switching apoptosis to necrosis. In
      cells depleted of glutathione, GSNO and DETA/NO induced rapid necrosis, which
      resulted from rapid depletion of ATP due to inhibition of glycolysis. Glycolytic
      intermediate 3-phosphoglycerate decreased DETA/NO-induced necrosis and increased
      apoptosis. We conclude that: (i). NO-induced apoptosis is mediated by H(2)O(2);
      (ii). NO-induced necrosis is mediated by energy failure speeded by thiol
      depletion.

PMID- 14642395
TI  - The oral iron chelator ICL670A (deferasirox) does not protect myocytes against
      doxorubicin.
AB  - The oral iron chelating agent ICL670A (deferasirox) and the clinically approved
      cardioprotective agent dexrazoxane (ICRF-187) were compared for their ability to
      protect neonatal rat cardiac myocytes from doxorubicin-induced damage.
      Doxorubicin is thought to induce oxidative stress on the heart muscle through
      iron-mediated oxygen radical damage. While dexrazoxane was able to protect
      myocytes from doxorubicin-induced lactate dehydrogenase release, ICL670A, in
      contrast, depending upon the concentration, synergistically increased or did not
      affect the cytotoxicity of doxorubicin. This occurred in spite of the fact that
      ICL670A quickly and efficiently removed iron(III) from its complex with
      doxorubicin, and rapidly entered myocytes and displaced iron from a fluorescence
      quenched trapped intracellular iron-calcein complex. Continuous exposure of
      ICL670A to either myocytes or Chinese hamster ovary (CHO) cells resulted in
      cytotoxicity while treatment of CHO cells with the ferric complex of ICL670A did
      not. These results suggest that ICL670A was cytotoxic either by removing or
      withholding iron from critical iron-containing proteins. Electron paramagnetic
      resonance spectroscopy was used to show that neither ICL670A nor its ferric
      complex were able to generate free radicals in either oxidizing or reducing
      systems suggesting that its cytotoxicity is not due to radical generation.

PMID- 14642396
TI  - Beta-carotene cleavage products after oxidation mediated by hypochlorous acid--a
      model for neutrophil-derived degradation.
AB  - After beta-carotene failed in certain clinical efficacy trials, there is evidence
      that the carotenoid might even be harmful, especially to smokers, when given in
      high dosages. These negative effects might be mediated in part also by carotenoid
      cleavage products (CPs) having a high reactivity towards biomolecules. The
      authors postulate that in certain tissues oxidative, nonenzymatic cleavage of
      carotenoids is carried out primarily by oxidants liberated by polymorphonuclear
      leukocytes (PML). In this study, we show that beta-carotene is degraded by
      stimulated PML in vitro. This gives the pathophysiological meaning to our further
      experiments in which beta-carotene degradation by hypochlorous acid and
      consecutive CP formation were investigated. While formation of apo-carotenals
      under these conditions has been studied before, this was not the case for short
      chain products. Performing gas chromatography mass spectrometry, we were able to
      identify for the first time 5,6-epoxi-beta-ionone, ionene, beta-cyclocitral, beta
      ionone, dihydroactinidiolide, and 4-oxo-beta-ionone as CPs formed after
      degradation of beta-carotene mediated by hypochlorous acid. Our findings may be
      of biological relevance because beta-carotene CPs are highly reactive and,
      therefore, potentially toxic.

PMID- 14642397
TI  - Hyperglycemia increases mitochondrial superoxide in retina and retinal cells.
AB  - Oxidative stress is believed to play a significant role in the development of
      diabetic retinopathy. In this study, we have investigated the effects of elevated
      glucose concentration on the production of superoxide anion by retina and retinal
      cells, the cellular source of the superoxide, the effect of therapies that are
      known to inhibit diabetic retinopathy on the superoxide production, and the role
      of the superoxide in cell death in elevated glucose concentration. Superoxide
      release was measured from retinas collected from streptozotocin-diabetic rats (2
      months) treated with or without aminoguanidine, aspirin, or vitamin E, and from
      transformed retinal Muller cells (rMC-1) and bovine retinal endothelial cells
      (BREC) incubated in normal (5 mM) and high (25 mM) glucose. Diabetes (retina) or
      incubation in elevated glucose concentration (rMC-1 and BREC cells) significantly
      increased superoxide production, primarily from mitochondria, because an
      inhibitor of mitochondrial electron transport chain complex II normalized
      superoxide production. Inhibition of reduced nicotinamine adenine dinucleotide
      phosphate (NADPH) oxidase or nitric oxide synthase had little or no effect on the
      glucose-induced increase in superoxide. Treatment of diabetic animals with
      aminoguanidine, aspirin, or vitamin E for 2 months significantly inhibited the
      diabetes-induced increase in production of superoxide in the retinas. Despite the
      increased production of superoxide, no increase in protein carbonyls was detected
      in retinal proteins from animals diabetic for 2-6 months or rMC-1 cells incubated
      in 25 mM glucose for 5 d unless the activities of calpain or the proteosome were
      inhibited. Addition of copper/zinc-containing superoxide dismutase to the media
      of rMC-1 and BREC cells inhibited the apoptotic death caused by elevated glucose.
      Diabetes-like glucose concentration increases superoxide production in retinal
      cells, and the superoxide contributes to impaired viability and increased cell
      death under those circumstances. Three therapies that inhibit the development of
      diabetic retinopathy all inhibit superoxide production, raising a possibility
      that these therapies inhibit retinopathy in part by inhibiting a hyperglycemia
      induced increase in superoxide production.

PMID- 14642398
TI  - Cytosolic and mitochondrial ROS in staurosporine-induced retinal cell apoptosis.
AB  - In this study, we investigated the involvement of reactive oxygen species (ROS)
      and calcium in staurosporine (STS)-induced apoptosis in cultured retinal neurons,
      under conditions of maintained membrane integrity. The antioxidants idebenone
      (IDB), glutathione-ethylester (GSH/EE), trolox, and Mn(III)tetrakis (4-benzoic
      acid) porphyrin chloride (MnTBAP) significantly reduced STS-induced caspase-3
      like activity and intracellular ROS generation. Endogenous sources of ROS
      production were investigated by testing the effect of the following inhibitors: 7
      nitroindazole (7-NI), a specific inhibitor of the neuronal isoform of nitric
      oxide synthase (nNOS); arachidonyl trifluoromethyl ketone (AACOCF(3)), a
      phospholipase A(2) (PLA(2)) inhibitor; allopurinol, a xanthine oxidase inhibitor;
      and the mitochondrial inhibitors rotenone and oligomycin. All these compounds
      decreased caspase-3-like activity and ROS generation, showing that both
      mitochondrial and cytosolic sources of ROS are implicated in this mechanism. STS
      induced a significant increase in intracellular calcium concentration
      ([Ca(2+)](i)), which was partially prevented in the presence of IDB and GSH/EE,
      indicating its dependence on ROS generation. These two antioxidants and the
      inhibitors allopurinol and 7-NI also reduced the number of TdT-mediated dUTP nick
      end labeling-positive cells. Thus, endogenous ROS generation and the rise in
      intracellular calcium are important inter-players in STS-triggered apoptosis.
      Furthermore, the antioxidants may help to prolong retinal cell survival upon
      apoptotic cell death.

PMID- 14642399
TI  - Oxidation and nitrosylation of oxyhemoglobin by S-nitrosoglutathione via nitroxyl
      anion.
AB  - The reaction between low molecular weight S-nitrosothiols and hemoglobin is often
      used to synthesize S-nitrosohemoglobin, a form of hemoglobin suggested to be
      involved in the regulation of vascular oxygen delivery. However, this reaction
      has not been studied in detail, and several groups have reported a variable co
      formation of oxidized methemoglobin (metHb) during synthesis. This study examines
      the mechanism of metHb formation and shows that nitrosylhemoglobin (HbNO) can
      also be formed. Generation of metHb and HbNO is largely dependent on the presence
      of protein thiol groups. We present evidence for a mechanism for the formation of
      metHb and HbNO involving the intermediacy of nitroxyl anion. Specifically, the
      reaction of nitroxyl with S-nitrosothiols to liberate nitric oxide and reduced
      thiol is proposed to be central to the reaction mechanism.

PMID- 14642400
TI  - Fibrates in 2003: therapeutic action in atherogenic dyslipidaemia and future
      perspectives.
AB  - OBJECTIVES: To explore the therapeutic potential of fibrates to attenuate
      premature atherosclerosis and cardiovascular disease in the atherogenic
      dyslipidemias typical of Type II diabetes, Metabolic Syndrome, and the Type IIB
      (mixed) lipid phenotype; such dyslipidemias frequently feature peripheral
      insulinoresistance. BACKGROUND: Recent epidemiological data reveal that a marked
      increase in the prevalence of Type II diabetes, obesity and the Metabolic
      Syndrome has occurred on a worldwide scale. Dyslipidemia is an integral component
      of the metabolic perturbations which characterise these disorders, and is
      intimately associated with premature atherosclerosis and elevated cardiovascular
      risk. The atherogenic dyslipidemias of Type II diabetes, the Metabolic Syndrome
      and mixed (IIB) hyperlipidemia feature moderate to marked elevation of
      triglyceride-rich lipoproteins, low HDL-C cholesterol levels, and a dense LDL
      phenotype; equally, they feature an inflammatory state. Fibrates, agonists of
      PPARalpha, act to modulate the expression of key genes of lipid transport and
      metabolism in organs such as the liver and adipose tissue; equally, they exert
      pleiotropic, anti-inflammatory effects downregulating expression of genes
      encoding acute phase proteins and inflammatory cytokines. By inducing elevation
      of HDL-C levels, reduction in triglyceride-rich lipoproteins and a shift in the
      dense LDL phenotype to receptor-active, buoyant LDL, and by diminishing the
      inflammatory state, fibrates act to attenuate the atherosclerotic burden in
      atherogenic dyslipidemia. Such actions translate into significant clinical
      benefit as demonstrated by the reduction in cardiovascular morbi-mortality
      observed in both primary and secondary intervention trials (VA-HIT, Helsinki
      Heart Study, SENDCAP, DAIS, BECAIT). CONCLUSIONS: Fibrate therapy represents a
      cost effective approach to the clinical management of a wide spectrum of
      atherogenic dyslipidemias involving low HDL-C and elevated TGRL levels, and which
      include Type II diabetes and the Metabolic Syndrome. Optimised clinical
      application of these lipid modulating, anti-inflammatory drugs in these disorders
      in the context of either monotherapy or in combination with low dose statin is,
      therefore, warranted.

PMID- 14642401
TI  - Inhibition of arterial cells proliferation in vivo in injured arteries by
      hyaluronan fragments.
AB  - It has been demonstrated previously that administration of high levels of high
      molecular mass hyaluronan (hyaluronic acid, HA) to rats was able to reduce in a
      significant way neointima formation in the injured arteries. In the present
      study, our aim was to verify whether small forms of HA (4-16 saccharides) are
      still able to reduce the proliferative response of ASMC to aortic injury. Treated
      rats received a total of 8 injections of a fixed dose of HA fragments (27 mg/kg
      rat contained in a volume of 550 microl). Two injections were given on the day of
      balloon catheter injury (BCI): one, intravenous, 10 min before BCI and one,
      subcutaneous, immediately after the BCI. The others injections (subcutaneous)
      were at 2, 4, 6, 8, 10 and 12 days after BCI. Control rats received an equivalent
      volume of the dissolving buffer containing only hyaluronidase, which has been
      destroyed before injection to rats. Neointima formation was analysed 14 days
      after the BCI. Intima-media wet weight and DNA content were significantly reduced
      in rats receiving HA fragments in comparison to controls (2P=0.01 for wet weight
      and 0.03 for DNA). This finding was confirmed by the histomorphometric study
      which showed that both neointima area and the ratio neointima/neointima+media
      were significantly decreased in treated rats (2P=0.03 for intima area and 0.049
      for the ratio). Our data showed thus and for the first time that administration
      of HA fragments with a very low molecular mass (4-16 saccharides) reduces the
      proliferative reaction of aorta to injury in vivo. In conclusion, HA fragments,
      which are components with an excellent safety profile, may offer hope for the
      prevention of restenosis after angioplasty.

PMID- 14642402
TI  - Oxidised lipoproteins may promote inflammation through the selective delay of
      engulfment but not binding of apoptotic cells by macrophages.
AB  - During normal tissue homeostasis apoptotic cells (AC) are rapidly recognised and
      engulfed by neighbouring cells or macrophages (Mphi), thus preventing an
      inflammatory response. Conversely, in chronically inflamed tissues, including the
      atherosclerotic artery and rheumatoid joint, removal of AC is defective despite
      the co-localisation of seemingly adequate numbers of Mphi. Mechanisms preventing
      removal of AC in vivo remain obscure, but might include oxidised low-density
      lipoprotein (ox-LDL), which is abundant in chronic inflammatory lesions. Although
      implicated in their pathogenesis, defining the role of ox-LDL on inflammatory
      processes has proved complicated. In fact, seemingly contradictory results have
      previously been described, though these may in part reflect the heterogeneous
      nature of ox-LDL applied in these studies. We wished to investigate the effect of
      physiologically representative ox-LDL on the binding and engulfment of apoptotic
      vascular smooth muscle cells (VSMC) and fibroblasts, as these have previously
      been shown to co-localise with Mphi in chronically inflamed tissues in vivo. We
      show that Mphi recognition of AC in vitro is not affected at physiological levels
      of ox-LDL. However, engulfment of intact AC is dramatically reduced/delayed.
      Importantly, in the absence of ox-LDL rapid phagocytosis of intact AC suppresses
      Mphi inflammatory cytokine release. In striking contrast, in the presence of ox
      LDL, despite binding of AC to Mphi, release of IL-6 and MCP-1 is no longer
      suppressed. We propose that ox-LDL could maintain an inflammatory response by
      inhibiting the engulfment of AC, required for Mphi de-activation. This mechanism
      may contribute to chronic persisting inflammation in the atherosclerotic artery
      and rheumatoid joint.

PMID- 14642403
TI  - Smoking-dependent association between paraoxonase 1 M/L55 genotype and coronary
      atherosclerosis in males: an autopsy study.
AB  - High-density lipoprotein-associated paraoxonase 1 (PON1) enzyme can retard the
      oxidation of lipids. The methionine for leucine substitution at position 55
      (M/L55) of the PON1 protein is associated with lower (MM genotype) or higher (ML
      or LL genotype) expression of the gene affecting serum level of PON1. We studied
      the association of the PON1 M/L55 genotype with the extent of atherosclerosis in
      an autopsy series of Finnish males. Areas of the coronary arteries and the aorta
      covered with fatty streaks and fibrotic and complicated lesions were measured
      from a total of 700 cases. Carriers of the MM genotype (14.4% of subjects) had
      larger percentual areas of fatty streaks in their left anterior descending
      coronary artery (P=0.014) and right coronary artery (P=0.004), as well as in
      thoracic (P<0.001) and abdominal aorta (P=0.010) compared to carriers of the LL
      or ML genotype. A PON1 genotype-by-smoking interaction was observed on the area
      of fatty streaks in left anterior descending coronary artery (P=0.011) and right
      coronary artery (P=0.005); the association between fatty streaks and MM genotype
      was evident only among non-smokers, whereas in smokers this association was
      abolished. The areas of more advanced atherosclerotic lesions did not vary
      significantly between the genotype groups. These data suggest that the genetic
      variation of PON1 affects the formation of early atherosclerotic lesions and that
      the effect is modified by smoking.

PMID- 14642404
TI  - Different migratory and proliferative properties of smooth muscle cells of
      coronary and femoral artery.
AB  - In the human coronary arteries, the intima begins to thicken from early
      adolescence and shows progressive thickening with age. We compared the response
      to vascular injury of the coronary and femoral arteries using a canine model.
      Both incorporation of 5-bromo-2'-deoxyuridine (BrdU) and neointimal formation
      after balloon injury were significantly greater in the coronary artery than in
      the femoral artery. Also, the proliferative and migratory activities of coronary
      smooth muscle cells (SMCs) were significantly greater than those of femoral SMCs
      in vitro. The level of phosphorylated myosin light chain (phospho-MLC) was higher
      in coronary SMCs than in femoral SMCs. Y-27632, a specific inhibitor of Rho
      kinase, significantly inhibited the PDGF-induced migration of both coronary and
      femoral SMCs. In contrast, the migration of coronary SMCs, but not femoral SMCs,
      was inhibited by ML-9, a specific inhibitor of myosin light chain kinase (MLCK).
      These findings suggest that the contribution of Rho-kinase and MLCK differs
      between the different arteries. They also suggest that a neointima develops more
      easily in the coronary artery than in the femoral artery because of the greater
      proliferative and migratory activity of coronary SMCs. Differential activation of
      MLC might partly explain the increased proliferation and migration of coronary
      SMCs.

PMID- 14642405
TI  - Mice deficient in apolipoprotein E but not LDL receptors are resistant to
      accelerated atherosclerosis associated with obesity.
AB  - The aims of this study were to determine whether mice induced to become obese
      also exhibited accelerated atherosclerosis, and to determine whether obesity
      itself or dyslipidemia associated with obesity enhanced atherosclerosis. Wild
      type (C57BL/6) mice and mice deficient for the low density lipoprotein receptor
      (LDLR-/-) or apolipoprotein E (apoE-/-) were fed a low fat, rodent chow diet or a
      high fat, high sucrose (diabetogenic) diet to induce obesity. As compared with
      wild-type mice, diabetogenic diet-fed LDLR-/- mice became more obese and
      developed severe dyslipidemia. Consequently, atherosclerotic lesions were
      increased in the LDLR-/- mice 3.7-fold over chow fed values. ApoE-/- mice showed
      weight gain profiles similar to those observed for wild-type mice. However, no
      differences in plasma lipid levels, lipoprotein profiles or atherosclerotic
      lesion areas were observed between chow-fed and diabetogenic diet-fed apoE-/-
      mice. These data demonstrate that lipid storage and partitioning as mediated by
      the low density lipoproteins (LDL) receptor or apoE-/- have profound and opposing
      consequences for dyslipidemia and atherosclerosis susceptibility associated with
      obesity.

PMID- 14642406
TI  - Regulation of selenoprotein GPx4 expression and activity in human endothelial
      cells by fatty acids, cytokines and antioxidants.
AB  - Phospholipid hydroperoxide glutathione peroxidase (GPx4) is the only antioxidant
      enzyme known to directly reduce phospholipid hydroperoxides within membranes and
      lipoproteins, acting in conjunction with alpha-tocopherol to inhibit lipid
      peroxidation. Peroxidation of lipids has been implicated in a number of
      pathophysiological processes, including inflammation and atherogenesis. We
      investigated the relative positive and negative effects of specific
      polyunsaturated fatty acids (PUFAs) and inflammatory cytokines on the activity
      and gene expression of the selenium-dependant redox enzyme GPx4. In human
      umbilical vein endothelial cells (HUVEC), GPx4 mRNA levels and activity were
      increased optimally by 114 nM selenium (as sodium selenite). Docosahexaenoic acid
      (DHA) and conjugated linoleic acid (CLA) further increased mRNA levels whereas
      arachidonic acid (ARA) had no effect; enzyme activity was decreased by DHA, was
      unaffected by CLA or was increased by ARA. GPx4 protein levels increased with
      selenium, ARA and DHA addition but not with CLA. Interleukin-1beta (IL-1beta)
      increased GPx4 mRNA, protein and activity whereas TNFalpha at 1 ng/ml increased
      activity while at 3 ng/ml it reduced activity and mRNA. Conversely, alpha
      tocopherol reduced mRNA levels without affecting activity. These results indicate
      that lipids, cytokines and antioxidants modulate GPx4 in a complex manner that in
      the presence of adequate selenium, may favour protection against potentially
      proatherogenic processes.

PMID- 14642407
TI  - Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in
      apolipoprotein-E-deficient mice.
AB  - Anti-angiogenic therapy reduces both plaque growth and intimal neovascularization
      in apolipoprotein-E-deficient mice (apoE-/-). Vascular endothelial growth factor
      (VEGF) has been suggested as playing a role in the development of
      atherosclerosis. We examined the hypothesis that VEGF and VEGF receptor-2 (VEGFR
      2) expression is upregulated in apoE-/- and, since it could be driven by
      oxidative stress, tested whether dietary supplementation with vitamins C and E
      could downregulate it.Two-month-old apoE-/- received vitamin C combined with
      alpha- or beta-tocopherol for 4 weeks. Aortic VEGF and VEGFR-2 expression were
      measured by RT-qPCR and western blot.ApoE-/- showed significantly higher
      expression of aortic VEGF and VEGFR-2 mRNA (P<0.001) and protein (P<0.001) than
      wild-type mice, as well as increased plasma VEGF (P<0.001). Vitamin C and alpha
      tocopherol significantly reduced aortic VEGF and VEGFR-2 expression in apoE-/-
      (P<0.001), circulating VEGF (P<0.01) and plasma lipid peroxidation (P<0.01). apoE
      /- receiving vitamin C and beta-tocopherol showed diminished lipid peroxidation
      and VEGFR-2, but only partial reduction of VEGF expression. These data
      demonstrate that augmented VEGF and VEGFR-2 expression in apoE-/- vasculature can
      be downregulated by vitamins C and E, at least partially through oxidative stress
      reduction. This novel mechanism could contribute to explaining the beneficial
      effects of antioxidant vitamins in experimental atherosclerosis.

PMID- 14642408
TI  - Metabolic risk markers in an overweight and normal weight population with
      oversampling of carriers of the IRS-1 972Arg-variant.
AB  - The relationship between the Gly972Arg polymorphism in the insulin receptor
      substrate-1 (IRS-1) gene and metabolic risk markers is not clear, possibly due to
      small sample sizes. Modification by body mass index (BMI) has also been
      suggested. Our aim was therefore to quantify the association of this 972Arg
      variant with insulin, glucose and lipid levels in overweight and non-overweight
      subjects with oversampling of subjects with the 972Arg-variant. We first
      genotyped 3684 subjects selected from a large population-based cohort (n
      approximately 23000) according to BMI (26-40 or 18-24 kg/m(2)). Next, we examined
      600 of these subjects for fasting metabolic risk markers according to BMI-group
      and genotype. Subjects with the 972Arg-variant had significantly higher insulin
      concentrations (4.09 pmol/l or 9.6%, P=0.024) and lower triglyceride levels (0.13
      mmol/l or 11%, P=0.001) compared with non-carriers when adjusted for age, sex,
      waist-to-hip ratio, BMI, alcohol consumption, physical activity and cigarette
      smoking. These associations were more pronounced in the high BMI-group, although
      the interactions were not statistically significant. Our large population-based
      sample shows that the IRS-1 Gly972Arg polymorphism relates to higher fasting
      insulin levels and lower triglyceride levels. The impact of this genotype and its
      modification by overweight may be smaller than suggested previously.

PMID- 14642409
TI  - Arterial stiffness is rapidly induced by raising the plasma homocysteine
      concentration with methionine.
AB  - Homocysteine appears to be causally related to cardiovascular disease and shown
      to induce endothelial dysfunction. An adverse effect on large elastic arteries
      has not been reported. In 18 healthy middle-aged subjects, systemic arterial
      compliance (SAC) was measured over 5h after a standard methionine load. Arterial
      pressure waves from the carotid artery and aortic flow were measured non
      invasively and SAC calculated. Differences in mean SAC values when plasma
      homocysteine concentrations were raised with a methionine containing meal and on
      another day when a control meal was eaten were highly significant. SAC fell
      (arterial stiffness increased) by 22% at 2.5h and by 19% at 5h (treatment x time
      interaction: P=0.003 and 0.004, respectively). Adjustment for confounders (age,
      arterial pressure, BMI, LDL cholesterol) did not affect conclusions. Thus,
      arterial stiffness in the central elastic arterial system increased rapidly at
      high plasma homocysteine concentrations.

PMID- 14642410
TI  - Antiatherothrombotic effects of nicotinic acid.
AB  - Cardiovascular event reduction in hypercholesterolemic subjects appropriately
      emphasizes the prominent role of statin therapy; however, niacin (nicotinic acid)
      is also an effective lipid-altering agent that prevents atherosclerosis and
      reduces cardiovascular events. Niacin has multifarious lipoprotein and anti
      atherothrombosis effects that improve endothelial function, reduce inflammation,
      increase plaque stability, and diminish thrombosis. Niacin reduces the
      atherogenicity of low-density lipoprotein (LDL) by changing the distribution of
      small LDL to large LDL subclass, and the susceptibility of LDL to oxidative
      modification. It is the most effective agent for increasing high-density
      lipoprotein cholesterol. Moreover, it favorably alters high-density lipoprotein
      composition, increasing apolipoprotein AI relative to apolipoprotein AII. Niacin
      reduces blood viscosity through a variety of mechanisms, thus improving blood
      flow and perfusion through stenotic segments of the vasculature. Finally, niacin
      has cardioprotective effects that may limit ischemia-reperfusion injury. By
      preserving glycolysis during periods of ischemia and improving subendocardial
      blood flow during reperfusion, niacin can improve the functional recovery of the
      myocardium.

PMID- 14642411
TI  - Influence of hydrogenated fat and butter on CVD risk factors: remnant-like
      particles, glucose and insulin, blood pressure and C-reactive protein.
AB  - Dietary trans fatty acids/partially-hydrogenated fat has been associated with
      increased risk of developing cardiovascular disease (CVD), possibly greater than
      predicted from changes in lipoprotein levels. To explore this issue further
      potential risk factors were assessed in subjects provided with each of six diets
      in randomized order containing as the major source of fat: soybean oil, semi
      liquid margarine, soft margarine, shortening, traditional stick margarine or
      butter. Plasma fatty acid profiles reflected diet, with triglyceride and
      phospholipid subfractions affected to a greater extent than cholesteryl ester.
      Non-fasting LDL-cholesterol levels were 144+/-27, 141+/-27, 146+/-26, 148+/-30,
      151+/-29 and 165+/-31 mg/dl (P<0.001) and total cholesterol/HDL-cholesterol
      ratios were 5.50+/-1.25, 5.54+/-1.50, 5.69+/-1.29, 5.82+/-1.40, 6.11+/-1.30 and
      5.94+/-1.43 (P=0.011), respectively, whereas other lipoprotein levels were not
      significantly different. Remnant-like particles levels were unaffected by dietary
      fat, either in the fasting or non-fasting state. Differences in fasting insulin
      and glucose levels were small and would not be predicted to have a large impact
      on glucose homeostasis. There was no significant effect of dietary fat type on C
      reactive protein levels or blood pressure. These data suggest that, as previously
      demonstrated, the major CVD risk factor adversely affected by dietary trans fatty
      acids/partially-hydrogenated fat is LDL-cholesterol levels and total
      cholesterol/HDL-cholesterol ratios.

PMID- 14642412
TI  - Normalization of daytime triglyceridemia by simvastatin in fasting
      normotriglyceridemic patients with premature coronary sclerosis.
AB  - Postprandial hyperlipidemia is associated with premature coronary sclerosis in
      fasting normolipidemic subjects. Self-determined daytime capillary triglyceride
      (cTG) profiles were compared between 26 fasting normotriglyceridemic patients
      with premature coronary artery disease (CAD) and 26 controls matched for gender,
      age and BMI. Daytime triglyceridemia was calculated as total area under the cTG
      curve (cTG-AUC). Total and LDL cholesterol were not different between CAD
      patients (5.4+/-0.8 mmol/l and 3.6+/-0.7 mmol/l, respectively) and controls
      (5.0+/-0.9 mmol/l and 3.3+/-0.8 mmol/l, respectively). Patients with CAD were
      characterized by a 44% higher cTG-AUC than matched controls (P<0.01). Using
      logistic regression analysis, cTG-AUC was the strongest predictor of the presence
      of CAD (P<0.001). Adding apo AI to the model improved the predictive power from
      71 to 77%. Sixteen patients were studied after increasing doses of simvastatin up
      to 80 mg/day. Although the target for LDL cholesterol was reached by simvastatin
      20mg/day, significant effects on cTG-AUC were found only by higher doses of
      simvastatin. Simvastatin 40 mg/day decreased cTG-AUC by 28% (P<0.05 versus
      baseline), reaching comparable values as in controls, without further improvement
      with simvastatin 80 mg/day (26% reduction versus baseline; P<0.05). Daytime
      triglyceridemia is linked to premature coronary sclerosis in fasting
      normotriglyceridemic patients. A higher dose of simvastatin was needed to
      normalize daytime triglyceridemia than was required to "normalize" LDL
      cholesterol.

PMID- 14642413
TI  - Influence of Chlamydia pneumoniae infection on aortic stiffness in healthy young
      men.
AB  - Though Chlamydia pneumoniae infection has been implicated in the pathogenesis of
      atherosclerosis, its role in early atherogenesis has not been well elucidated. To
      clarify whether C. pneumoniae infection was related to early atherogenesis, we
      evaluated the association between serological detection of C. pneumoniae
      antibodies and aortic stiffness in 102 healthy young male volunteers (mean age
      27.1+/-0.4 years). Serum C. pneumoniae IgA and IgG antibodies were measured by
      the enzyme-linked immunosorbent assay (ELISA). Aortic stiffness was estimated
      using the brachial-ankle pulse wave velocity (PWV). No significant differences
      were observed between IgA seropositive and seronegative groups with regard to
      conventional cardiovascular risk factors. However, the mean PWV value was
      significantly higher in the IgA seropositive group than the seronegative group.
      Analyses of subgroups according to C-reactive protein (CRP) level showed that
      those subjects with IgA seropositivity and a high CRP level (>0.17 mg/l) had the
      highest PWV values. Multivariate logistic regression analysis revealed that a
      combination of C. pneumoniae IgA seropositivity and a high CRP level was an
      independent predictor of high values of PWV. These results suggest that C.
      pneumoniae infection might contribute to early atherogenesis, which might be
      associated with chronic inflammation.

PMID- 14642414
TI  - The hypertriglyceridemic waist phenotype among women.
AB  - BACKGROUND: Elevated plasma triglycerides (TG) and waist girth
      (hypertriglyceridemic waist (HTGW)) has been associated with elevated insulin,
      small dense low-density lipoprotein (sLDL) particles, and Apo B in men. The HTGW
      has not been reported for women and the effect of cardiorespiratory fitness
      ("fitness") on associations between HTGW and coronary risk factors is unknown.
      PURPOSE: To determine the prevalence of HTGW and the influence of fitness on the
      relationship between HTGW and coronary risk among 137 healthy women (54+/-9 year;
      body mass index (BMI)=28+/-6 kg/m(2)). METHODS: HTGW was defined as waist girth
      >88 cm and TG >150 mg/dl. The metabolic triad was defined as insulin >31 pmol/l,
      Apo B >69 mg/dl and LDL-C >84 mg/dl. Fitness was assessed with a maximal
      treadmill exercise test. RESULTS: The sample prevalence of HTGW (n=15) was 11%
      (95% CI=5.7-16.0%). Apo B (P=0.04) and insulin (P=0.0001) increased across
      quintiles of waist girth, and LDL-C (P=0.004) increased across quintiles of TG.
      Metabolic triad prevalence was highest (67%, n=10) among HTGW women and lowest
      (22%, n=26) among non-HTGW women. A trend for higher coronary heart disease CHD
      risk factors was observed among HTGW compared with non-HTGW women. Among the HTGW
      group, a trend for lower CHD risk factors was observed among fit (>or=6.5 METs,
      n=7) versus unfit women (<6.5 METs, n=8). Sample size limitations prohibited
      meaningful tests of significant differences in CHD risk factors when stratified
      simultaneously on HTGW and fitness status. CONCLUSIONS: HTGW is associated with
      increased coronary risk factors similarly among women as reported for men. Higher
      fitness may improve the CHD risk profile among women with HTGW.

PMID- 14642415
TI  - Modulation of HDL metabolism by probucol in complete cholesteryl ester transfer
      protein deficiency.
AB  - Probucol, an antioxidative and hypolipidemic agent, has been postulated to
      increase reverse cholesterol transport by enhancing cholesteryl ester transfer
      protein (CETP) activity. However, its clinical implication in CETP deficient
      patients has not been fully defined. To characterize the effects of probucol in
      the absence of CETP, we evaluated the changes in lipid profile, lipid
      peroxidation, and paraoxonase 1 (PON1) activity in two complete CETP deficient
      patients, caused by treatment with probucol. When the patients were not receiving
      probucol, low-density lipoprotein (LDL) particles were smaller and high-density
      lipoprotein (HDL) particles were larger in these patients than in controls.
      Treatment with probucol (500 mg/day) resulted in the decrease in the levels of
      HDL-C and apolipoprotein (apo) A-I up to 22%. The size of HDL particles became
      smaller. LDL cholesterol concentration did not change in one patient, while it
      decreased by 47% in the other. PON1 activity/HDL-C, which was about 40% lower in
      the patients before treatment than in controls with the matching PON1 genotype,
      increased by 30% during the treatment. Lag time for LDL and HDL in both cases
      became prolonged more than 1.8 times after administration of probucol. This study
      demonstrated for the first time that probucol reduces HDL-C even in humans with
      complete CETP deficiency. Probucol treatment in these patients was also
      associated with protection of lipoproteins against oxidative stress, suggesting a
      clinical benefit of this drug even in such a state.

PMID- 14642416
TI  - Site-specific progression of carotid artery intimal-medial thickness.
AB  - PURPOSE: To characterize the intercorrelation of changes in intimal-medial
      thickness (IMT) among carotid artery sites and examine the influence of diabetes
      and sex on these correlations. METHODS: Ultrasonographic IMT measurements from
      the near and far walls of common and internal segments in the arteries of 1207
      participants of the Insulin Resistance Atherosclerosis Study (IRAS) were analyzed
      to estimate the underlying correlations of IMT changes (average of 5.2 years)
      among artery sites after correction for measurement error. RESULTS: Differences
      in IMT progression associated with diabetes and sex were evident at all sites.
      IMT changes were strongly correlated between left and right arteries (r=0.32
      0.73) and near and far walls (r=0.42-0.87). Correlations of IMT changes at
      corresponding sites of internal versus common segments were reduced from r=0.32
      among normal individuals to r=0.09 among those with diabetes, but were similar
      for women and men. CONCLUSIONS: IMT progression is a diffuse process involving
      all carotid artery sites. Diabetes does not influence the bilateral and radial
      nature of progression, but reduces the correlation between distal sites within an
      artery. Pooling measurements across arteries and walls often yields the most
      efficient analyses.

PMID- 14642417
TI  - Molecular dynamics in ferroelectric 4-aminopyridinium tetrachloroantimonate(III),
      [4-NH2C5H4NH][SbCl4].
AB  - Proton spin-lattice relaxation time and second moment of polycrystalline [4
      NH2C5H4NH][SbCl4] have been determined at 160-400 K, at 90 and 25 MHz. The
      temperature dependence of the second moment indicates that the cation is in the
      "frozen" state over that temperature range, while at higher temperatures it
      oscillates at an angle of 135 degrees to the pseudo-six-fold axis of the aromatic
      ring. Weak influence of different phase transitions on the temperature
      dependences of relaxation times T1 and T1D can be explained in terms of molecular
      dynamics.

PMID- 14642418
TI  - Unusual observation of nitrogen chemical shift anisotropies in tetraalkylammonium
      halides by 14N MAS NMR spectroscopy.
AB  - 14N Magic-angle spinning (MAS) NMR spectra for a number of polycrystalline,
      symmetrical tetraalkylammonium halides with short alkyl chains (C2H(5)- to n
      C4H(9)-) have been recorded following a careful setup of the experimental
      conditions. Analysis of the spectra demonstrates the presence of 14N chemical
      shift anisotropies (CSAs) on the order of |delta sigma| = 10-30 ppm along with
      14N quadrupole coupling constants in the range of 10-70 kHz. The magnitude and
      sign of the CSAs determined from 14N MAS NMR are confirmed by recording and
      analysis of the corresponding slow-speed spinning (500-650 Hz) 15N CP/MAS NMR
      spectra. Most interestingly, it is observed experimentally and demonstrated
      theoretically and by simulations, that these CSAs are reflected in the spinning
      sideband (ssb) intensities of the 14N MAS spectra at much higher spinning speeds
      than can be applied to retrieve the corresponding 15N CSAs from the ssb pattern
      in the 15N CP/MAS spectra.

PMID- 14642419
TI  - Solid-state NMR studies of the adsorption and photooxidation of ethanol on mixed
      TiO2--SnO2 photocatalysts.
AB  - In situ solid-state NMR methodologies have been used to investigate the
      photocatalytic oxidation of ethanol (CH3CH2OH) over a series of SnO2-based
      photocatalysts. The adsorption of ethanol on commercially available SnO2 powder
      was studied using both cross-polarization 13C NMR and REDOR experiments, and
      showed the formation of two surface ethanol species, hydrogen-bonded ethanol at
      surface hydroxyl groups and ethanol chemisorbed to the SnO2 surface (Sn-
      OCH2CH3). 13C NMR of the adsorbed ethanol was used to characterize the surface of
      monolayer SnO2--TiO2 coupled photocatalysts supported on porous Vycor glass. In
      situ solid-state NMR studies showed that the photooxidation of ethanol over the
      monolayer photocatalysts was slower than that over a supported TiO2 monolayer
      photocatalyst due to the build-up of reaction intermediates such as acetic acid
      on the catalyst surface. 119Sn NMR experiments characterized the tin species on
      the porous Vycor glass support.

PMID- 14642420
TI  - Magnetic alignment in nominally non-magnetic hexagonal metal hydrides: NMR.
AB  - Powders of three hexagonal metal-hydrides or -deuterides are found to align in
      4.4-8.3 T magnetic fields used for NMR. The field-alignment is unexpected, since
      all three systems have very small susceptibilities, as demonstrated by sharp NMR
      lines. The extent of alignment runs from nearly complete to barely detectable in
      ZrBe2(H,D)x, LuD3, and YD3, respectively. The preferred alignment direction in
      ZrBe2(H,D)x is with the crystallites' c-axis perpendicular to B, while the c-axis
      and B tend to be parallel in LuD3 and YD3. The susceptibilities chi parallel and
      chi perpendicular are determined from bulk magnetization measurements in aligned
      ZrBe2H1.4 powder. The alignment must be considered for proper analysis of NMR
      spectra in these and related materials.

PMID- 14642421
TI  - The transient processes in multi-pulse nitrogen-14 NQR.
AB  - It has been demonstrated that transient processes, observed in a single crystal
      of NaNO2 acted upon by pulse sequences MW-2 and MW-4 and their modifications with
      180 degrees flip angle of the pulses (Solid State Nucl. Magn. Resonance 10 (1997)
      63; Sov. Phys.-JETP 88(5) (1999) 1580), which manifest themselves in the
      oscillating form of the NQR signals envelope, can be explained in the frames of a
      two-particle model. It has been proved that the nature of echo signals in the
      effective field of multi-pulse sequences received by the inversion of the phase
      of the sequence pulses or by introducing an additional 180 degrees pulse is
      connected with re-focusing of accumulated digressions of the flip angle from the
      ideal 180 degrees pulse. Experimental results of observing single and multiple
      echoes in a number of powdered nitrogenated substances in the effective field of
      various sequences at room temperature have been presented.

PMID- 14642422
TI  - 29Si and 19F MAS NMR spectra of isolated 29Si(19F)2 and 29Si(19F)3 spin systems:
      experiments and simulations.
AB  - We consider 29Si and 19F MAS NMR spectra of isolated 29Si(19F)2 and 29Si(19F)3
      spin systems in two organosilicon compounds of the type RR'SiF2 and RSiF3(R,R' =
      organic ligands). Experimental spectra are analysed by means of numerical
      simulations. It is found that the SiF3 group in RSiF3 is reorienting rapidly
      around the molecular Si-C bond direction in the solid state. The two 19F
      shielding tensors in RR'SiF2 have strongly differing orientations relative to the
      two Si-F bond directions in the molecule. Possibilities and limitations of
      straightforward MAS NMR approaches for the full characterisation of 29Si(19F)2
      and 29Si(19F)3 spin systems and other dipolar coupled two and three-spin systems
      are discussed.

PMID- 14642423
TI  - Intracerebroventricular injection of apelin-13 reduces food intake in the rat.
AB  - Apelin is a peptide recently identified as a ligand for the APJ receptor, a
      receptor located in tissues such as the small intestine and in the hypothalamus.
      Apelin has been detected in adipose tissue, gastrointestinal tract, heart and
      stomach. Recent reports suggest a role for apelin in the regulation of blood
      pressure and the control of body fluid homeostasis. The present studies examined
      the consequences on food intake of intravenous (IV) and intracerebroventricular
      (ICV) injection of apelin-13 in the Wistar rat. IV injection of 10 nmol of apelin
      13 did not cause any change in food intake in either fed or 24-h fasted rats. ICV
      injection of 1 and 3 nmol of apelin-13 resulted in a reduction in food intake in
      both fed and fasted rats. The earliest reduction in food intake occurred at 4 h
      post-injection in fed rats. In fasted rats, food intake was reduced at 24-h post
      injection only. These data provide evidence of a possible role for apelin-13 in
      the control of food intake.

PMID- 14642424
TI  - Role of the nitric oxide/cyclic GMP pathway and ascorbic acid in 3
      morpholinosydnonimine (SIN-1)-induced increases in dopamine secretion from PC12
      cells. A microdialysis in vitro study.
AB  - We showed previously, using in vitro microdialysis, that activation of the nitric
      oxide (NO)/cyclic GMP pathway was the underlying mechanism of exogenous NO
      induced dopamine (DA) secretion from PC12 cells. In this study, infusion of the
      potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1, 1.0 mM for 60
      min) induced a long-lasting decrease in dialysate DA+3-methoxytyramine (3-MT) in
      dialysates from PC12 cell suspensions. Ascorbic acid (0.2 mM) co-infusion allowed
      SIN-1 to increase dialysate DA+3-MT. SIN-1+ascorbic acid effects were abolished
      by Ca(2+) omission. Infusion of high K(+) (75 mM) induced a 2.5-fold increase in
      dialysate DA+3-MT. The increase was inhibited by SIN-1 co-infusion. Conversely,
      co-infusion of ascorbic acid (0.2 mM) with SIN-1+high K(+) resulted in a 3.5 fold
      increase in dialysate DA+3-MT. The L-type Ca(2+) channel inhibitor nifedipine
      selectively inhibited the DA+3-MT increase pertaining to high K(+), while the
      soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3]quinoxalin-1
      one selectively inhibited the increase pertaining to SIN-1 effects. These results
      suggest that activation of the NO/sGC/cyclic GMP pathway is the underlying
      mechanism of extracellular Ca(2+)-dependent effects of SIN-1 on DA secretion from
      PC12 cells. Extracellular Ca(2+) entry occurs through nifedipine-insensitive
      channels. Ascorbic acid is a key determinant in modulating the distinct profiles
      of SIN-1 effects.

PMID- 14642425
TI  - Circadian heme oxygenase activity in the hamster suprachiasmatic nuclei.
AB  - Entrainment of mammalian circadian rhythms requires the activation of specific
      signal transduction pathways in the hypothalamic suprachiasmatic nuclei (SCN). We
      have tested the participation of heme oxygenase (HO) in the SCN, by assessing HO
      specific activity at different time points and photic conditions. HO activity was
      determined by the conversion of hemin to bilirubin. HO enzymatic activity in the
      SCN was significantly higher during the night than during the day; this
      difference persisted when animals were placed under constant darkness, suggesting
      an endogenous circadian control. HO inhibition by Zn-protoporphyrin did not
      affect light-induced phase shifts in vivo, suggesting that the enzyme is not
      necessary for light input to the clock.

PMID- 14642426
TI  - The inhibitory effect of ginseng saponins on the stress-induced plasma
      interleukin-6 level in mice.
AB  - The effect of ginseng saponins on plasma interleukin-6 (IL-6) in non-stressed and
      immobilization-stressed mice were investigated. Ginseng total saponins,
      ginsenosides Rb2, Rg1 and Rd administered intraperitoneally attenuated the
      immobilization stress-induced increase in plasma IL-6 level. But,
      intracerebroventricular injection of each ginsenoside did not affect plasma IL-6
      level induced by immobilization stress. Ginsenosides Rb2, Rd and Rg1
      significantly decreased norepinephrine and/or epinephrine-induced increase of IL
      6 level in macrophage cell line (RAW 264.7). Thus, it can be suggested that the
      inhibitory action of ginseng saponins against the immobilization stress-induced
      increase of plasma IL-6 level would be in periphery; at least in part, mediated
      by blocking norepinephrine- and/or epinephrine-induced increase of IL-6 level in
      macrophage rather than in the brain. Ginseng saponins might be proposed as a
      possible candidate in the research or therapeutic modulation of stress-related
      disorders.

PMID- 14642427
TI  - Concomitant distribution shift of glial GABA transporter and S100 calcium-binding
      proteins in the rat retina after kainate-induced excitotoxic injury.
AB  - The goal of this study was to elucidate the involvement of neuronal and glial
      calcium-binding proteins in the stimulation of gamma-aminobutyric acid (GABA)
      transport system by kainate-induced excitotoxicity in the rat retina. We used
      immunohistochemical method to assess the localization of GABA reuptake and
      calcium-binding proteins. After systemic administration of kainate, the neuronal
      GABA transporter does not show an association with calbindin D-28K. However, the
      localization of the GAT-3 transport system in Muller glial cells is closely
      correlated with the S100 proteins interacting with glial fibrillary acidic
      protein (GFAP) in response to kainate injury. Furthermore, we demonstrate that
      kainate-mediated excitotoxicity induced concomitant distribution shift of glial
      GABA transporter, S100 proteins and GFAP in the distal processes and endfeet of
      glial cells during the first 48 h.

PMID- 14642428
TI  - Effective treatment with fucoidin for perinatal hypoxic-ischemic encephalopathy
      in rats.
AB  - Leukocyte-endothelial adhesion is a key step to initiate post-ischemic
      reperfusion injury in many organs. In this study, we found that the expressions
      of P-selectin mRNA and protein were increased in the ipsilateral hemisphere with
      a peak at 8 h after hypoxia-ischemia in immature brain. Such temporal profiles of
      P-selectin expression followed by hypoxia-ischemia are consistent with a role in
      the subsequent brain injury. Because fucoidin is known to inhibit P/L-selectin
      mediated leukocyte adhesion, we examined whether the treatment of fucoidin
      attenuates hypoxia-ischemia-induced neural damages. Treatment with fucoidin
      exhibited a substantial neuroprotective effect in a dose-dependent manner and
      inhibited the leukocyte adhesion significantly, as revealed by myeloperoxidase
      activity. These results suggest that anti-adhesion strategy may be an effective
      therapeutic application for the perinatal hypoxic-ischemic encephalopathy.

PMID- 14642429
TI  - Microneurographic study of C fiber discharges induced by CO2 laser stimulation in
      humans.
AB  - We investigated C-fiber discharges and cerebral potentials evoked by weak CO(2)
      laser beams applied to a tiny skin area in five healthy subjects.
      Microneurography was performed from the peroneal nerve in the right popliteal
      area. Cerebral potentials were recorded from the Cz electrode referred to linked
      earlobes. The mean conduction velocity of five stable single units was 1.1+/-0.3
      m/s. The mean latency of the positive peak of cerebral potentials was 1327.4+/
      46.2 ms. These findings indicated that this new stimulation method selectively
      activated C-fiber nociceptors of the skin.

PMID- 14642430
TI  - Neuronal expression of cell cycle-related proteins after brain ischaemia in man.
AB  - The death of neurons after brain ischaemia may be associated with activation of
      cyclin-dependent kinases (CDKs) and upregulation of cyclins, reflecting aberrant
      entry of neurons into the cell cycle. Little has been published on the expression
      of cell cycle proteins after brain ischaemia in man. Well-characterized antisera
      were therefore used to examine the neuronal expression of CDK2, CDK4 and cyclins
      A, D1 and E in sections of brain from patients who had experienced cardiac arrest
      or focal brain infarction, and died 3.5 h to 9 days later. Scattered neurons
      contained elevated levels of cyclin D1, CDK2 and, to a lesser extent, CDK4, but
      little or no cyclin A or E. Present findings indicate that brain ischaemia
      induces the entry of some neurons from G0 into the G1 phase of the cell cycle,
      and suggest a potential therapeutic role for CDK inhibitors in ischaemic stroke.

PMID- 14642431
TI  - Corticospinal excitability in patients with unilateral sciatica.
AB  - Patients suffering from sciatica may develop altered patterns of corticospinal
      drive to muscles of the leg. Electromyographic recordings were made bilaterally
      from tibialis anterior and lateral gastrocnemius muscles during transcranial
      magnetic stimulation of the motor cortex from nine patients with unilateral
      sciatica and seven healthy controls. The mean thresholds for eliciting motor
      evoked potentials (MEPs) and the silent period were higher in the patients than
      in the control subjects. In addition, there was a positive correlation between
      the patients' self rated score of disability (the Oswestry Disability Index) and
      their threshold for MEPs and the silent period. This study suggests that the
      chronic pain experienced by the patients leads to a reduction in corticospinal
      drive to the legs. These changes might help to relax muscles close to the
      perceived site of pain and so alleviate symptoms. Investigation of these patients
      following remedial treatment will allow us to establish if the changes are
      transient in nature.

PMID- 14642432
TI  - Increased corticortropin-releasing hormone release in ovariectomized rats'
      paraventricular nucleus: effects of electroacupuncture.
AB  - Utilizing push-pull perfusion, we examined secretary profiles of corticotropin
      releasing hormone (CRH) in the nucleus paraventricularis (PVN) of freely moving
      intact (INT) and ovariectomized (OVX) rats, and in the meanwhile the effects of
      electroacupuncture (EA) on the release patterns of CRH were observed. The PVN was
      perfused with artificial cerebrospinal fluid between 08:00 and 12:00 h, and
      perfusates were collected every 10 min. The average CRH output was significantly
      larger in OVX rats than that in INT and INT with EA (INT+EA) groups.
      Interestingly enough, the CRH output showed a significant elevation in OVX with
      EA (OVX+EA) group during the EA procedure and further increase immediately after
      the EA. It is the first time to present the temporal profiles of CRH secretion in
      the PVN of OVX and OVX+EA rats.

PMID- 14642433
TI  - Treadmill exercise suppresses food-deprivation-induced increase of nitric oxide
      synthase expression in rat paraventricular nucleus.
AB  - Exercise is known to potentially affect the eating patterns. In the present
      study, the effect of treadmill exercise on the expressions of nitric oxide
      synthase (NOS) and neuronal nitric oxide synthase (nNOS) in the paraventricular
      nucleus (PVN) of food-deprived rats was investigated using nicotinamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nNOS
      immunohistochemistry. The present results showed that food deprivation increased
      NOS and nNOS expressions in the PVN of the hypothalamus and treadmill exercise
      suppressed food deprivation-induced enhancing of NOS and nNOS expressions in the
      PVN. The most suppressive effect of treadmill exercise on the expressions of NOS
      and nNOS were observed in the heavy-intensity exercise group. Based on the
      present study, it is possible that treadmill exercise alleviates desire for food
      under food-deprivation conditions via modulation of NOS expression.

PMID- 14642434
TI  - Genetic influences on prepulse inhibition of startle reflex in humans.
AB  - Prepulse inhibition (PPI) is a suppression of the startle reflex that occurs when
      an intense startling stimulus is preceded by a weaker 'prepulse' stimulus. PPI
      deficits have been implicated in the biological bases of schizophrenia and some
      other neuropsychiatric disorders and proposed as a possible biological marker
      (endophenotype) for genetic studies. However, little is known about the genetic
      determination of PPI in humans. We examined acoustic eye-blink startle reflex and
      PPI in 142 young female twins (40 monozygotic and 31 dizygotic pairs) and
      conducted a biometrical genetic analysis using structural equation modeling. PPI
      showed significant heritability suggesting that over 50% of PPI variance in this
      sample can be attributed to genetic factors. Baseline startle magnitude showed
      higher heritability (about 70%).

PMID- 14642435
TI  - Lack of association between TrkA single nucleotide polymorphisms and sporadic
      Alzheimer's disease in a Japanese population.
AB  - Nerve growth factor and its receptor with tyrosine kinase activity (TrkA) have
      been implicated in the development of Alzheimer's disease (AD). Entire coding
      regions of TrkA gene harboring exons 1 through 17 were sequenced in 114 patients
      with sporadic AD and 112 control subjects in a Japanese population, and six known
      and two novel single nucleotide polymorphisms were identified, but no mutation
      associated with sporadic AD was identified. Concurrently, case-control analysis
      of TrkA gene A1674G polymorphism in 534 patients with sporadic AD and 454 control
      subjects has revealed no significant differences in TrkA genotype or allele
      frequencies even after stratification for Apolipoprotein E epsilon4 carrier
      statuses. Thus, the TrkA genotype does not appear to influence the risk of
      developing sporadic AD in a Japanese population.

PMID- 14642436
TI  - The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt
      ligands, is associated with the susceptibility to schizophrenia.
AB  - Neurodevelopmental abnormalities have been reported in studies on the
      pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a
      variety of processes in neurodevelopment, and the frizzled proteins have been
      identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3
      (FZD3) is required for formation of the neural crest and for development of major
      fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a
      positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3
      gene in patients with schizophrenia and control subjects in the Japanese
      population. We found a significant association between schizophrenia and the FZD3
      gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest
      that dysregulation of the Wnt-signaling pathway may be involved in the
      susceptibility to schizophrenia.

PMID- 14642437
TI  - Amyotrophic lateral sclerosis: disease stage related changes of tau protein and
      S100 beta in cerebrospinal fluid and creatine kinase in serum.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to
      progressive cell death of upper and lower motor neurons and reactive
      astrogliosis. Two proteins which may be relevant in this respect (tau and S100
      beta) were studied in cerebrospinal fluid (CSF) next to routine parameters in 20
      patients with sporadic ALS and 20 age-matched controls. Serum levels of creatine
      kinase (CK) were also determined to monitor the muscular involvement. S100 beta
      showed a significant decrease in CSF over the disease course (P=0.024). CSF tau
      as well as serum CK were elevated in 70% of the ALS patients. While highest CSF
      tau levels were found rather in the early disease stages, serum CK showed a shift
      of the peak values to several months later. Elevation of the CSF/serum albumin
      quotient occurred in 20% of the cases most likely representing a non-specific
      finding in ALS.

PMID- 14642438
TI  - Nicastrin gene in familial and sporadic Alzheimer's disease.
AB  - Nicastrin is a protein recently discovered associated to presenilins and involved
      in the production of amyloid beta peptide that accumulates in Alzheimer's disease
      (AD) brain. In this study the nicastrin gene was examined for unknown mutations
      and polymorphisms in 104 patients with familial AD (52 early-onset and 52 late
      onset), 174 sporadic AD and 191 healthy neurological controls of Italian origin.
      The scanning of the nicastrin gene identified a missense mutation (N417Y) in two
      patients with sporadic AD, in an early-onset familial AD and in a young control
      subject. Furthermore, we found two silent mutations and four intronic
      polymorphisms, three of them co-segregating in a single haplotype. We found some
      differences in the distribution of genotype alterations in the AD population
      compared to the controls. However, our data together with other evidence did not
      support the pathological role of missense mutation N417Y.

PMID- 14642439
TI  - Increased TNFalpha production and Cox-2 activity in organotypic brain slice
      cultures from APPsw transgenic mice.
AB  - beta-Amyloid (Abeta) peptides are the principal component of senile plaques and
      vascular deposits in Alzheimer's disease and are derived from the proteolytic
      cleavage of the beta-amyloid precursor protein (APP). We have previously shown
      that synthetic Abeta can stimulate cyclooxygenase-2 (Cox-2) activity in brain
      organotypic slice cultures. In the present study, we used brain slices from
      transgenic APP Swedish (TgAPPsw) mice and control littermates of different age
      groups to determine the effect of APP overexpression on the levels of
      prostaglandin and tumor necrosis factor alpha (TNFalpha) release. The production
      of eicosanoid and TNFalpha was increased as a function of age in organotypic
      brain slice culture from TgAPPsw mice compared to age matched control
      littermates. We also showed that the selective Cox-2 inhibitor NS-398 reduces the
      production of eicosanoid and TNFalpha in organotypic brain slice cultures of
      TgAPPsw mice. In conclusion, our data suggest that either activity or expression
      of Cox-2 is increased in TgAPPsw mice brains as a function of age, contributing
      to an increased production of pro-inflammatory eicosanoids and TNFalpha.

PMID- 14642440
TI  - Glutamic acid decarboxylase (GAD)67, but not GAD65, is constitutively expressed
      during development and transiently overexpressed by activity in the granule cells
      of the rat.
AB  - gamma-Aminobutyric acid (GABA)-mediated neurotransmission from the granule cells
      to CA3 is transiently expressed during the first 3 weeks of age in the rat. In
      the adult, seizures provoke this inhibitory signaling to reappear. To gain
      insight into the origin of GABA in these cells, we explored the expression of
      both isoforms of glutamic acid decarboxylase (GAD, 65 and 67 kDa), during
      development and after seizures in the adult rat. We found that GAD(67), but not
      GAD(65), is expressed in the mossy fibers of developing rats. In adults, GAD(67)
      is no longer detectable, unless seizures are induced. By contrast, GAD(65) is
      neither expressed in granule cells nor in their mossy fibers at any age nor after
      seizures, despite the presence of GAD(65) mRNA, confirmed by reverse
      transcription-polymerase chain reaction in situ.

PMID- 14642441
TI  - The human central nervous system needs time to organize task-specific covariation
      of finger forces.
AB  - We studied how the central nervous system (CNS) organizes outputs of effectors in
      a redundant motor task. During four-finger ramp force production, finger forces
      show positive covariations across trials at low forces, which turn into negative
      covariations at a critical force value (F(CR)). Subjects performed such tasks
      with different target amplitudes and durations of the ramp. F(CR) showed
      significant linear relations to the rate of force change. The slopes of the
      relations varied across subjects corresponding to a critical time (T(CR)) ranging
      from 0.13 to 0.84 s. Across subjects, T(CR) showed no relation to maximal force
      production; T(CR) increased with the ramp duration. We conclude that the CNS
      needs a certain time to organize stabilization of total force by a negative
      covariation among finger forces.

PMID- 14642442
TI  - Brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in Parkinson's
      disease and age of onset.
AB  - Given the implications with respect to neuronal survival and the decreased level
      of the protein in the striatal region in Parkinson's disease (PD), brain-derived
      neurotrophic factor (BDNF) may be a candidate gene conferring susceptibility to
      PD. In a recent study of a Japanese population, a functional BDNF Val66Met
      polymorphism was associated with PD, however, an analogous investigation of a
      western population did not replicate this finding. In the present study of a
      Chinese sample, we have investigated the associations between the BDNF
      polymorphism and susceptibility to PD and PD onset age. The distribution of the
      BDNF genotypes and alleles did not differ significantly comparing PD patients and
      controls. Further, the onset age was not significantly different comparing the
      three BDNF genotype groups. Thus, our negative findings suggest that it is
      unlikely that the BDNF Val66Met polymorphism plays a major role in the
      pathogenesis of PD in the Chinese population. Other BDNF genetic variants, and
      the association of these variants with PD symptomatology or treatment response,
      may merit further investigation.

PMID- 14642443
TI  - Selective dendrite-targeting of mRNAs of NR1 splice variants without exon 5:
      identification of a cis-acting sequence and isolation of sequence-binding
      proteins.
AB  - Both protein and mRNA for the NR1 subunit of N-methyl-D-aspartate receptors are
      present in neuronal dendrites and undergo changes in distribution following
      synaptic excitation. However, the expression of all exonic splice variants of NR1
      in dendrites has not been determined. In the present study, antibodies against
      the exon 5 (ex5) peptide sequence labeled proteins mostly in the soma of
      hippocampus neurons, whereas antibodies against ex21 or ex22 labeled cell bodies
      and dendrites. Antisense cRNAs for ex5 hybridized with mRNAs in cell bodies,
      whereas cRNAs for ex21 with mRNAs in both cell bodies and dendrites. Antisense
      DNA to a 24-base sequence identified as being present only in the 5'-UTR of cDNAs
      lacking ex5 (ex5(-)), hybridized with mRNAs in soma and dendrites and this
      labeling was coincident, mostly, with RNA granules. Insertion of the 24-base DNA
      ahead of that for enhanced green fluorescent protein (EGFP) increased the
      transport of EGFP mRNA and the expression of EGFP in neurites of neurons in
      culture. Fluorescent sense mRNA that contained the 24-base sequence bound to
      proteins in dendrites and to two proteins, 60 and 70 kDa, in brain microsomes.
      Proteins of similar size were also labeled by [32P]CTP-mRNA for NR1-(1a), which
      contains the 24-base 5'-UTR sequence, but not for NR1-(2b), which does not.
      Biotinylated 24-base sense mRNA was used to purify from brain microsomes two RNA
      binding proteins (60 and 70 kDa). We concluded that the 24-base sequence in 5'
      UTR of ex5(-) mRNA functioned as a cis-acting, dendrite-targeting element
      recognized selectively by two microsome proteins.

PMID- 14642444
TI  - Chronic carbamazepine treatment increases myristoylated alanine-rich C kinase
      substrate phosphorylation in the rat cerebral cortex via down-regulation of
      calcineurin A alpha.
AB  - Carbamazepine (CBZ) is generally used as a mood-stabilizing drug for the
      treatment of bipolar disorders. However, little is known about the molecular
      mechanisms of CBZ actions in the brain, which account for this therapeutic
      profile. In the present study, we examined the effects of chronic CBZ treatment
      on the protein kinase C (PKC) pathway. Male Wistar rats received injections of
      CBZ once daily for 3-5 weeks. The protein levels of PKC isozymes, calcineurin
      Aalpha subunit (CaN-Aalpha) and myristoylated alanine-rich C kinase substrate
      (MARCKS), and phosphorylation of MARCKS in the rat cerebral cortex were
      determined by immunoblot analysis. The content of CaN-Aalpha mRNA was determined
      by Northern blot analysis. Nomicr; significant changes were observed in PKC
      alpha, beta, gamma, delta and epsilon in the cytosol and membrane fractions after
      5 weeks of CBZ treatment. There were no significant changes in the actin-binding
      PKCepsilon. Interestingly, phosphorylation of MARCKS was increased more than
      twofold, while no significant changes were observed in MARCKS protein level in
      the cytosol fraction. Furthermore, CaN-Aalpha was significantly decreased at both
      the protein and mRNA levels. The level of MARCKS phosphorylation is reportedly
      regulated by the balance between PKC-mediated phosphorylation and CaN-mediated
      dephosphorylation. Our results indicate that chronic CBZ treatment increases
      MARCKS phosphorylation via decreasing the content of CaN-Aalpha. Phosphorylation
      of MARCKS has been reported to play an important role in the release of
      neurotransmitters, such as noradrenaline and serotonin. Therefore, the increase
      in phosphorylation of MARCKS observed only after chronic CBZ treatment may be
      related to the mood-stabilizing effects of CBZ.

PMID- 14642445
TI  - Investigation of the subunit composition and the pharmacology of the
      mitochondrial ATP-dependent K+ channel in the brain.
AB  - Selective activation of mitoK(ATP) channels can protect the brain or cultured
      neurons against a variety of anoxic or metabolic challenges. However, little is
      known about the subunit composition or functional regulation of the channel
      itself. In the present study, we sought to characterize the mitoK(ATP) channel in
      the mouse brain using overlapping approaches. First, we determined that
      mitochondria contain the pore-forming Kir6.1 and Kir6.2 subunits with Western
      blotting, immunogold electron microscopy and the identification of mitochondrial
      transport sequences. In contrast, we found no evidence for the presence of either
      known sulfonylurea receptors (SUR1 or SUR2) in the mitochondria. However, the ATP
      dependent K (K(ATP)) channel inhibitor glibenclamide specifically binds to
      mitochondria in both neurons and astrocytes, and small molecular weight SUR2-like
      proteins were concentrated in mitochondria. In addition to mice, similar results
      were found in rats and pigs. Second, live respiring mitochondria were stained
      with the membrane potential sensitive dye MitoFluorRed and visualized by confocal
      microscopy. We investigated the effects of pharmacological closing and opening of
      the channel with glibenclamide and the specific mitoK(ATP) openers diazoxide and
      BMS-191095. Closing of the channel inhibited the energization of the
      mitochondria, which was reversed by the application of the mitoK(ATP) openers. We
      also found that blocking mitochondrial peroxynitrite formation with FP15 has a
      similar effect to blocking the mitoK(ATP) channels. We conclude that brain
      mitochondria contain functional K(ATP) channels. The pore-forming subunit of the
      channel can be either Kir6.1 or Kir6.2, and the SUR subunit may be a SUR2 splice
      variant or a similar protein.

PMID- 14642446
TI  - Hyperglycolysis is exacerbated after traumatic brain injury with fentanyl vs.
      isoflurane anesthesia in rats.
AB  - Despite common use of narcotics in the clinical management of severe traumatic
      brain injury (TBI), in experimental models rats treated with fentanyl have
      exhibited worse functional outcome and more CA1 hippocampal death than rats
      treated with standard isoflurane anesthesia. We hypothesized that greater post
      traumatic excitotoxicity, reflected by cerebral glucose utilization (CMRglu), may
      account for detrimental effects of fentanyl vs. isoflurane. Rats were
      anesthetized with either isoflurane (1% by inhalation) or fentanyl (10 mcg/kg iv
      bolus then 50 mcg/kg/h infusion). 14C-deoxyglucose autoradiography was performed
      45 min after controlled cortical impact (CCI) to left parietal cortex (n=4 per
      anesthetic group) or in uninjured rats after 45 min of anesthesia (n=3 per
      anesthetic group). Uninjured rats treated with fentanyl vs. isoflurane showed 35
      45% higher CMRglu in all brain structures (p<0.05) except CA3. After TBI in rats
      treated with isoflurane, CMRglu increased significantly only in ipsilateral CA1
      and ipsilateral parietal cortex (p<0.05 vs. isoflurane uninjured). Conversely,
      after TBI in rats treated with fentanyl, CMRglu increased markedly and
      bilaterally in CA1 and CA3 (p<0.05 vs. fentanyl uninjured), but not ipsilateral
      parietal cortex. In contralateral CA1, CMRglu was nearly two times greater after
      TBI in fentanyl vs. isoflurane treated rats (p<0.05). Hyperglycolysis was
      exacerbated in CA1 and CA3 hippocampus after TBI in rats treated with fentanyl
      vs. isoflurane anesthesia. This post-traumatic hyperglycolysis suggests greater
      excitotoxicity and concurs with reports of worse functional outcome and more CA1
      hippocampal death after TBI with fentanyl vs. isoflurane anesthesia.

PMID- 14642447
TI  - Oral uridine pro-drug PN401 decreases neurodegeneration, behavioral impairment,
      weight loss and mortality in the 3-nitropropionic acid mitochondrial toxin model
      of Huntington's disease.
AB  - Huntington's disease (HD) is associated with decreased activity of mitochondrial
      succinate dehydrogenase (complex II). De novo biosynthesis of uridine nucleotides
      is directly coupled to the respiratory chain. Cells with impaired mitochondrial
      function become uridine auxotrophs and can be maintained with high micromolar
      concentration of uridine and pyruvate. The therapeutic role of pyrimidines and
      possible changes in uridine content has not been assessed in neurological
      diseases involving mitochondrial dysfunction in vivo. Oral administration of
      PN401 delivers much higher levels of uridine to the circulation than oral
      administration of uridine itself. Administration of complex II inhibitor 3
      nitropropionic acid (3NP) induced neuronal damage in the striatum, substantia
      nigra and/or thalamus in 80% of the mice and led to 38% mortality. Treatment with
      PN401 almost completely prevented the neuronal damage due to 3NP and completely
      prevented mortality. In two subsequent experiments, 3NP-induced weight loss,
      mortality and behavioral impairment in rotarod performance and spontaneous motor
      activity were attenuated by treatment with oral PN401. 3NP did not reduce
      forebrain total uridine nucleotides (TUN), though higher doses of PN401
      associated with optimal neuroprotection did elevate TUN to supranormal levels.
      Thus, oral PN401 treatment has neuroprotective effects in a HD model of
      mitochondrial dysfunction and the mechanism is more complex than correction of a
      pyrimidine deficit.

PMID- 14642448
TI  - Differential effects of NK1 receptors in the midbrain periaqueductal gray upon
      defensive rage and predatory attack in the cat.
AB  - This study utilized anatomical and behavioral-pharmacological methods to
      determine the role of NK(1)-Substance P receptors in the midbrain periaqueductal
      gray (PAG) in defensive rage behavior in cats. For behavioral pharmacological
      experiments, monopolar stimulating electrodes were implanted in the medial
      hypothalamus for elicitation of defensive rage behavior and cannula-electrodes
      were implanted in the PAG for microinjections of receptor compounds.
      Microinjections of the NMDA antagonist, AP-7 (2 nmol), into the dorsal PAG
      blocked defensive rage elicited by medial hypothalamic stimulation, thus
      establishing the PAG as a synaptic region that receives hypothalamic inputs
      linked to defensive rage behavior. Microinjections of the NK(1) agonist, GR73632,
      into the same injection sites facilitated defensive rage in a dose-dependent
      manner, and also induced spontaneous hissing in five cats. The effects of GR73632
      were reduced by pretreatment of the PAG with the NK(1) antagonist, GR82334 (16
      nmol), microinjected into the same sites. Microinjections of GR73632 (8 nmol)
      into the PAG also suppressed predatory attack elicited by stimulation of the
      lateral hypothalamus. Immunohistochemical methods utilized to detect Substance P
      and Fos immunoreactivity revealed that neurons in the PAG activated after
      defensive rage-inducing medial hypothalamic stimulation lie in the same region as
      Substance-P-immunoreactive processes. Fos immunoreactivity was highest in the
      dorsomedial aspect of the rostral PAG after medial hypothalamic stimulation. Cats
      that were unstimulated or that exhibited predatory attack after lateral
      hypothalamic stimulation had low c-fos expression levels in the PAG. Substance P
      immunoreactivity was high throughout the dorsal PAG. The results indicate that
      NK(1) receptors in the PAG potentiate defensive rage and suppress predatory
      aggression in the cat.

PMID- 14642449
TI  - Circadian variations in expression of the trkB receptor in adult rat hippocampus.
AB  - The expression of brain-derived neurotrophic factor (BDNF) in the central nervous
      system (CNS) and the expression of its high-affinity trkB receptor on neuron
      surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and
      protein) and trkB mRNA shows circadian oscillations in rat hippocampal
      homogenates. We investigated circadian variations in trkB expression in specific
      areas of the adult rat hippocampal formation by immunohistochemistry. In sets of
      two experiments performed in the spring, 39 2-month-old male Wistar rats were
      accustomed to a 12-h light-12-h dark cycle for 2 weeks. Three animals were then
      sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal
      formation were obtained and processed for trkB immunohistochemistry. Cell
      staining intensity was assessed by image analysis of different hippocampal areas
      on five sections per animal. Circadian rhythmicity was evaluated by the cosinor
      method. Statistically significant circadian variations in trkB expression were
      found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the
      hippocampus, with highest expression during the first half of the dark (activity)
      period. These findings suggest a relationship between trkB expression and the
      physiological neuronal activation of wakefulness. TrkB receptor expression in the
      hippocampal regions studied was continuous and changes were gradual over the 24-h
      cycle, suggesting that more complex regulatory mechanisms also intervened.

PMID- 14642450
TI  - Effect of alpha 2-adrenoceptor blockade on lithium action in the rat brain.
AB  - The inhibitory effect of different concentrations of lithium (0.15-10 x 10(-3) M)
      on cAMP production induced by isoprenaline (1 x 10(-4) M) after the blockade of
      alpha(2)-adrenoceptors in the rat cerebral cortex was investigated. Low lithium
      concentrations (0.3-0.6 x 10(-3) M) exerted a significant inhibitory effect after
      yohimbine (1 x 10(-5) M) addition, but had no effect when isoprenaline alone or
      prazosin (1 x 10(-7) M) was added. The recovery of [3H]yohimbine binding after
      irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
      (EEDQ) was evaluated in cortical membranes to study how alpha(2)-adrenoceptor
      repopulation affects the action of lithium on the adenylyl cyclase-cAMP system.
      When the density of alpha(2)-adrenoceptors was lower than 21%, lithium showed a
      significant inhibitory effect at all concentrations tested. However, at higher
      densities, increased concentrations of lithium were required to inhibit cAMP
      production. Our results suggest that the inhibitory effect of lithium on cAMP
      levels in the rat brain is conditioned by alpha(2D)-adrenoceptors.

PMID- 14642451
TI  - Expression of bone morphogenetic proteins in the brain during normal aging and in
      6-hydroxydopamine-lesioned animals.
AB  - Bone morphogenetic proteins (BMPs), BMP receptors (BMPRs), and endogenous BMP
      antagonists have been found to be critically important for the development of the
      central nervous system (CNS) and peripheral organs in mammals. There is also
      increasing evidence that this system has significant activity in the adult CNS.
      Accordingly, we studied the regional distribution of endogenous BMP ligand
      proteins, receptors, and antagonists during aging and after lesion of the
      midbrain dopamine pathways produced by 6-hydroxydopamine (6-OHDA). We found that
      there were only small changes in the levels of these molecules as a function of
      age. Interestingly, levels of BMP 7 and noggin, a BMP antagonist, were uniquely
      elevated in substantia nigra. Moreover, after lesions of the midbrain dopamine
      system by 6-hydroxydopamine, there was a marked reduction in levels of all BMP
      ligands, receptors and antagonists bilaterally in both substantia nigra and
      hippocampus. There were also differential changes in BMP ligands, receptors, and
      antagonists in the cortex and striatum after such lesions. Taken together, our
      results indicate significant expression of BMP-related molecules in the adult and
      aging brain, and suggest a dynamic and differential regulation of these molecules
      after perturbations.

PMID- 14642452
TI  - Cilostazol reduces brain lesion induced by focal cerebral ischemia in rats--an
      MRI study.
AB  - To investigate the effects of cilostazol on the hemispheric ischemic lesion, we
      monitored the apparent diffusion coefficient (ADC) and T2 images by MRI
      techniques in comparison with histology at the terminal of and after 24-h
      reperfusion following 2-h occlusion of middle cerebral artery (MCA). The ADC
      values of tissue water and T2-weighted images were quantified by high field
      magnetic resonance. No significant difference was observed by ADC image among
      vehicle and cilostazol treatment groups when measured during MCA occlusion. Oral
      treatment with cilostazol 30 mg/kg two times at 5 min and 4 h significantly
      suppressed the hemispheric lesion area and volumes when detected by ADC, T2
      images and histology, but 3 and 10 mg/kg cilostazol were without effect.
      Cilostazol (30 mg/kg) significantly reduced the increased cerebral water content
      at the ischemic hemisphere compared with vehicle group. In line with these
      results, the neurological deteriorations were much improved in the cilostazol
      treated group. Taken together, it is concluded that post-treatment with
      cilostazol exerts a potent protective effect against cerebral infarct size by
      reducing the cytotoxic edema.

PMID- 14642453
TI  - Increased auditory startle response and reduced prepulse inhibition of startle in
      transgenic mice expressing a double mutant form of amyloid precursor protein.
AB  - Prepulse inhibition (PPI), a form of sensorimotor gating, occurs when an auditory
      startle response is markedly inhibited by a preceding sub-threshold stimulus
      (prepulse). Deficits in PPI have been demonstrated in patients with certain
      psychiatric disorders, such as schizophrenia, and in laboratory animals following
      specific pharmacological manipulations. Patients with Alzheimer's disease (AD)
      have not been tested in PPI, but have been shown to have abnormal sensory gating
      in another paradigm. Transgenic (Tg) CRND8 mice, which model Alzheimer's disease,
      carry the Swedish and Indiana familial Alzheimer's disease mutations of the human
      amyloid precursor protein gene and show age-related increases in beta-amyloid
      (Abeta) production, as well as plaque deposition. The present experiment
      investigated auditory startle threshold and PPI in TgCRND8 mice at various ages.
      In two longitudinal studies, PPI was examined in male TgCRND8 mice and non
      transgenic (non-Tg) controls at 6-8 weeks of age (pre-plaque), and every 2 weeks
      thereafter until all mice were at least 16 weeks old (post-plaque). In a cross
      sectional study, three different age sets of nai;ve TgCRND8 and non-Tg mice were
      tested: 10-12, 12-14, and 15-17 weeks old. In all three studies, TgCRND8 mice
      consistently and robustly demonstrated an enhanced response to a range of
      auditory startle stimuli compared to non-Tg mice. In addition, the TgCRND8 mice
      exhibited modest reductions in PPI, compared to non-Tg controls. These PPI
      deficits were present at pre- and post-plaque time points and did not appear to
      intensify with age; thus, they do not seem to correlate with the known
      neuropathology of TgCRND8 mice.

PMID- 14642454
TI  - Modulation of social learning in rats by brain corticotropin-releasing factor.
AB  - In order to investigate the impact of brain stress-related neuropeptide tone on
      learning and memory performance, juvenile recognition ability was examined in
      adult female rats using a social memory test following pharmacological
      inactivation and activation of corticotropin-releasing factor (CRF) systems. In
      particular, administration of a competitive CRF receptor antagonist [0.2, 1 or 5
      microg intracerebroventricular doses of D-Phe CRF (12-41)], dose dependently
      impaired learning performance over a 30-min delay to 27% of vehicle controls
      values. In complementary fashion, forgetting produced by a 120-min delay that
      impaired social recognition performance to 29% of 30-min delay control levels was
      reversed by administration of a 1-microg dose of the CRF binding protein ligand
      inhibitor, r/h CRF (6-33), although a higher 5 microg dose exerted non-specific
      effects on social investigation. These findings suggest that brain CRF systems
      are physiologically relevant for social memory capacity in the absence of
      stressor exposure.

PMID- 14642455
TI  - Different brain structures mediate drinking and sleep suppression elicited by the
      somatostatin analog, octreotide, in rats.
AB  - When injected into the cerebral ventricles, the somatostatin analog, octreotide
      (OCT) elicits prompt drinking, vasopressin secretion and increases in blood
      pressure that are attributed to the activation of the intracerebral
      angiotensinergic system. In addition, OCT induces sleep responses that might be
      mediated by an inhibition of hypothalamic neurons producing growth hormone
      releasing hormone (GHRH). OCT (0.02 microg in 0.2 microl) was microinjected into
      various brain sites to determine the structures inducing drinking and/or sleep
      suppression in response to OCT in rats. Drinking (>1 ml water in 10 min) was
      elicited in 17 rats out of 86 tested. The positive drinking sites resided in or
      around the subfornical organ (SFO) and the paraventricular nucleus. Both
      structures are part of the reported angiotensinergic dipsogenic circuit of the
      brain. These microinjections failed to elicit consistent sleep effects. Sleep
      suppression (>10% recording time in hour 1) was observed after injection of OCT
      either into the arcuate nucleus (n=7), where the majority of GHRHergic neurons
      reside, or into the medial preoptic area/anterior hypothalamus (n=8), where GHRH
      acts to promote sleep. Administration of OCT into far lateral sites of the
      lateral preoptic area and lateral hypothalamus stimulated sleep in hour 1 (n=10),
      perhaps via inhibiting cholinergic neurons previously implicated in arousal. The
      results are consistent with the hypothesis that somatostatin is involved in the
      regulation of both water intake and sleep, and suggest that different structures,
      and therefore different somatostatinergic neuronal pools, mediate these actions.

PMID- 14642456
TI  - Induction of brain glucose uptake by a factor secreted into cerebrospinal fluid.
AB  - It is well established that the carotid body receptors (CBR), at the bifurcation
      of the carotid artery, inform the brain of changes in the concentration of CO(2)
      and O(2) in arterial blood. More recent work suggests that these receptors are
      also extremely sensitive to blood glucose levels suggesting that they may play an
      important role as sensors of blood components important for brain energy
      metabolism. Much less is known about changes in brain glucose metabolism in
      response to CBR activation. Here we show that 2-8 min after local injection of
      sodium cyanide (NaCN) into the CBR or after electrical stimulation of the carotid
      sinus nerve in dogs and rats, brain glucose uptake increased fourfold.
      Cerebrospinal fluids (CSF) transferred from dogs, 2-8 min after CBR stimulation,
      into the cisterna magna of non-stimulated dogs or rats induced a similar increase
      in brain glucose uptake. CSF from stimulated dogs was also active when injected
      intravenously in anesthetized or awake rats. The activity was destroyed when the
      stimulated CSF was heated to 100 degrees C or treated with trypsin. We conclude
      that a peptide important for brain glucose regulation appears in the CSF shortly
      after CBR stimulation.

PMID- 14642457
TI  - Zen and the art of medical image registration: correspondence, homology, and
      quality.
AB  - Nonrigid registration (NRR) is routinely used in the study of neuroanatomy and
      function and is a standard component of analysis packages such as SPM. There
      remain many unresolved correspondence problems that arise from attempts to
      associate functional areas with specific neuroanatomy and to compare both
      function and anatomy across patient groups. Problems can result from ignorance of
      the underlying neurology which is then compounded by unjustified inferences drawn
      from the results of NRR. Usually the magnitude, distribution, and significance of
      errors in NRR are unknown so the errors in correspondences determined by NRR are
      also unknown and their effect on experimental results cannot easily be
      quantified. In this paper we review the principles by which the presumed
      correspondence and homology of structures is used to drive registration and
      identify the conceptual and algorithmic areas where current techniques are
      lacking. We suggest that for applications using NRR to be robust and achieve
      their potential, context-specific definitions of correspondence must be developed
      which properly characterise error. Prior knowledge of image content must be
      utilised to monitor and guide registration and gauge the degree of success. The
      use of NRR in voxel-based morphometry is examined from this context and found
      wanting. We conclude that a move away from increasingly sophisticated but context
      free registration technology is required and that the veracity of studies that
      rely on NRR should be keenly questioned when the error distribution is unknown
      and the results are unsupported by other contextual information.

PMID- 14642458
TI  - Evaluation of voxel-based morphometry for focal lesion detection in individuals.
AB  - Voxel-based morphometry (VBM) is an automated statistical technique used to
      detect regional differences in tissue density and tissue amount based on
      spatially standardized structural magnetic resonance (MR) images. Developed
      initially to discern differences between groups of subjects, VBM is now being
      used to characterize structural abnormalities in individual brains. While VBM
      performance has been qualitatively assessed for this purpose, to date no
      quantitative validation study has been performed. This study evaluated several
      commonly used variants of VBM for detecting structural differences at the
      individual level by assessing their performance in MR images of 10 subjects with
      stable focal brain lesions. Results were quantitatively compared to expert
      tracings of the lesions, the current gold standard for lesion detection and
      delineation. Additionally, analyses using two sets of simulated lesion data were
      performed to examine the relative impact of the underlying processing steps on
      VBM results. Performance metrics revealed that (1) for this application, VBM had
      low sensitivity; (2) detection sensitivity was altered by model parameterization;
      (3) underperformance was due to the adverse influence of lesions on the
      preprocessing steps and to insufficient statistical power; and (4) VBM could not
      satisfactorily delineate the spatial extent of lesions, even in simulations that
      avoided preprocessing artifacts. In its current form, VBM is not a suitable stand
      alone technique for detecting or spatially characterizing focal lesions.

PMID- 14642459
TI  - Connectivity analysis with structural equation modelling: an example of the
      effects of voxel selection.
AB  - Structural equation modelling (SEM) of neuroimaging data is commonly applied to a
      network of distributed brain regions. We applied SEM to an fMRI dataset to
      identify condition-specific effects in a simple experiment composed of visual
      stimulation and baseline conditions. The visual network was composed of three
      well-defined anatomical regions (V1, V2, and V5) and three path connections (V1 -
      > V2, V1 --> V5, and V2 --> V5). This network was used to test four hypotheses:
      (1) whether the condition-specific effects for all three connections vary
      according to the data selected for modelling; (2) whether the "summary" measures
      that are often used are indeed appropriate; (3) whether measures taken from the
      voxel timecourse can reliably predict the condition-specific effects for each one
      of the three path connections, and (4) whether all voxels within an anatomical
      region yield equivalent SEM outcomes. There was some variability in the
      significance of the condition-specific effects across randomly selected voxels
      within regions. However, the SEM outcome from the "summary" measures was
      comparable to the most frequent pattern of condition-specific effects. Magnitude,
      delay, spread, and goodness-of-fit measures taken from a gamma fit to the voxel
      time courses predicted reliably the significance of the SEM condition-specific
      effects for each connection. This result enabled us to identify spatially
      coherent regions at the boundaries of V2 that displayed different condition
      specific effects from those seen in the majority of the voxels. Although the
      generality of these results awaits further investigation, this example highlights
      a number of important issues for SEM. We have provided further evidence that the
      SEM outcome does vary somewhat according to the voxels selected and that,
      although the use of summary measures can give a generalised view of the
      connectivity pattern, they could fail to capture functional differences within
      specialised areas.

PMID- 14642460
TI  - Geometric atlas: modeling the cortex as an organized surface.
AB  - Recent atlases of the cortical surface are based on a modelization of the
      cerebral cortex as a topological sphere. This captures effectively its
      organization as a regular bidimensional sheet of layers parallel to the surface
      and with perpendicular cortical columns. Yet, while in the vertical direction
      cortices are almost the same throughout phylia, in the sense of its surface the
      cerebral cortex is one of the most variable and distinctive parts of the nervous
      system. Indeed, gyri and sulci appear to have a crucial organizing role in an
      architectonic, connectional, and functional sense. This organization is not
      explicitly captured by the surface model of the cortex. We propose a geometric
      model of the cortical anatomy based on flat representations of principal sulci
      obtained from surface reconstructions of MRI data, and on neuroanatomical and
      theoretical considerations concerning the folding patterns of the cortex. The
      cortex is modeled by a sphere where primary sulci are included as axes. The
      arrangement of the axes is a simplification of the arrangement of principal sulci
      observed in flat stereographic representations of the whole cortical surface. The
      position of secondary and tertiary sulci is then defined by a field of
      orientations parallel and orthogonal to the axes. We consider the use of the
      geometric model as a synthetic reference cortex for addressing reconstructions of
      cortical surfaces. We present a method which establishes a bijection between the
      geometric model and a cortical surface reconstruction by using the axes of the
      model as boundary conditions for a set of partial differential equations solved
      over both surfaces. Using the geometric model as atlas provides a natural
      parameterization of the cortical surface that, unlike angular coordinates, allows
      for a localization based on the surface distance to its main organizing landmarks
      and folding patterns.

PMID- 14642461
TI  - From will to action: sequential cerebellar contributions to voluntary movement.
AB  - The cerebellum is known to be involved in numerous motor related functions, but
      recent observations suggest that it also performs fundamental operations on
      nonmotor functions such as perception and cognition. Assuming that the cerebellum
      has to be consulted in a limited window of time, cerebellar activation should
      occur in a time-dependent manner in respect to the corresponding telencephalic
      areas. This hypothesis was tested by combining a simple motor task with the
      demand of a self-paced delay using event-related functional magnetic resonance
      imaging. Evaluation with a time-shifted canonical hemodynamic response function
      revealed spatially and temporally separated cerebral and cerebellar activation
      accompanying the entire process--from conscious planning to final motor output-
      within a time frame of 6 s. The cerebral activations spread from the anterior
      cingulate cortex through the supplementary motor and premotor area to the primary
      motor and sensory cortices. This cascade was temporally in parallel with
      cerebellar activations propagating from the neo- to the spinocerebellum. An early
      lateral cerebellar recruitment 3 s prior movement onset confirms its involvement
      in cognitive processing. A later medial activation occurring close to movement
      onset most probably reflects spinocerebellar kinesthetic feedback. Between these
      two points a striking lateromedial succession was found, which is in line with
      the hypothesis of the existence of multiple internal models residing in the
      cerebellum, each communicating with its own corresponding telencephalic region.

PMID- 14642462
TI  - Spatiotemporal characteristics of hemodynamic changes in the human lateral
      prefrontal cortex during working memory tasks.
AB  - The prefrontal cortex (PFC) is widely believed to subserve mental manipulation
      and monitoring processes ascribed to the central executive (CE) of working memory
      (WM). We attempted to examine and localize the CE by functional imaging of the
      frontal cortex during tasks designed to require the CE. Using near-infrared
      spectroscopy, we studied the spatiotemporal dynamics of oxygenated hemoglobin
      (oxy-Hb), an indicator of changes in regional cerebral blood flow, in both sides
      of lateral PFC during WM intensive tasks. In most participants, increases in oxy
      Hb were localized within one subdivison during performance of the n-back task,
      whereas oxy-Hb increased more diffusely during the random number generation (RNG)
      task. Activation of the ventrolateral PFC (VLPFC) was prominent in the n-back
      task; both sustained and transient dynamics were observed. Transient dynamics
      means that oxy-Hb first increases but then decreases to less than 50% of the peak
      value or below the baseline level before the end of the task. For the RNG task
      sustained activity was also observed in the dorsolateral PFC (DLPFC), especially
      in the right hemisphere. However, details of patterns of activation varied across
      participants: subdivisions commonly activated during performance of the two tasks
      were the bilateral VLPFCs, either side of the VLPFC, and either side of the DLPFC
      in 4, 2, and 4 of the 12 participants, respectively. The remaining 2 of the 12
      participants had no regions commonly activated by these tasks. These results
      suggest that although the PFC is implicated in the CE, there is no stereotyped
      anatomical PFC substrate for the CE.

PMID- 14642463
TI  - Performing allocentric visuospatial judgments with induced distortion of the
      egocentric reference frame: an fMRI study with clinical implications.
AB  - The temporary improvement of visuospatial neglect during galvanic vestibular
      stimulation (Scand. J. Rehabil. Med. 31 (1999)117) may result from correction of
      the spatial reference frame distorted by the responsible lesion. Prior to an
      investigation of the neural basis of this effect in neurological patients,
      exploration of the neural mechanisms underlying such procedures in normals is
      required to provide insight into the physiological basis thereof. Despite their
      clinical impact, the neural mechanisms underlying the interaction of galvanic
      (and other) vestibular manipulations with visuospatial processing (and indeed the
      neural bases of how spatial reference frames are computed in man) remain to be
      clarified. We accordingly used fMRI in normal volunteers to investigate the
      effect of galvanically induced interference with the egocentric spatial reference
      frame on the neural processes underlying allocentric visuospatial (line
      bisection) judgments. A significant specific interaction of galvanic vestibular
      stimulation with the neural mechanisms underlying allocentric visuospatial
      judgments was observed in right posterior parietal and ventral premotor cortex
      only. Activation of these areas previously found to be damaged in visuospatial
      neglect suggests that these effects reflect the increased processing demands when
      compensating for the distorted egocentric spatial reference frame while
      maintaining accurate performance during the allocentric spatial task. These
      results thus implicate right posterior parietal and right ventral premotor cortex
      in the computation of spatial reference frames. Furthermore, our data imply a
      specific physiological basis for the temporary improvement of visuospatial
      neglect in patients with right hemisphere lesions during galvanic vestibular
      stimulation and may thus impact upon the rehabilitation of neglect: understanding
      the interaction of galvanic vestibular stimulation with allocentric visuospatial
      judgments in healthy volunteers may lead to the more effective deployment of such
      techniques in neurological patients.

PMID- 14642464
TI  - Cortical capacity constraints for visual working memory: dissociation of fMRI
      load effects in a fronto-parietal network.
AB  - Working memory (WM) capacity limitations and their neurophysiological correlates
      are of special relevance for the understanding of higher cognitive functions.
      Evidence from behavioral studies suggests that restricted attentional resources
      contribute to these capacity limitations. In an event-related functional magnetic
      resonance imaging (fMRI) study, we probed the capacity of the human visual WM
      system for up to four complex nonnatural objects using a delayed discrimination
      task. A number of prefrontal and parietal areas bilaterally showed increased
      blood oxygen level-dependent activity, relative to baseline, throughout the task
      when more than one object had to be held in memory. Monotonic increases in
      response to memory load were observed bilaterally in the dorsolateral prefrontal
      cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely,
      activity in the frontal eye fields (FEFs) and in areas along the intraparietal
      sulcus (IPS) peaked when subjects had to maintain only two or three objects and
      decreased in the highest load condition. This dissociation of memory load effects
      on cortical activity suggests that the cognitive operations subserved by the IPS
      and FEF, which are most likely related to attention, fail to support visual WM
      when the capacity limit is approached. The correlation of brain activity with
      performance implies that only the operations performed by the DLPFC and pre-SMA,
      which support an integrated representation of visual information, helped subjects
      to maintain a reasonable level of performance in the highest load condition.
      These results indicate that at least two distinct cortical subsystems are
      recruited for visual WM, and that their interplay changes when the capacity limit
      is reached.

PMID- 14642465
TI  - Frontal activations associated with accessing and evaluating information in
      working memory: an fMRI study.
AB  - To investigate the involvement of frontal cortex in accessing and evaluating
      information in working memory, we used a variant of a Sternberg paradigm and
      compared brain activations between positive and negative responses (known to
      differentially tax access/evaluation processes). Participants remembered two
      trigrams in each trial and were then cued to discard one of them and maintain the
      other one as the target set. After a delay, a probe letter was presented and
      participants made decisions about whether or not it was in the target set.
      Several frontal areas--anterior cingulate (BA32), middle frontal gyrus (bilateral
      BA9, right BA10, and right BA46), and left inferior frontal gyrus (BA44/45)-
      showed increased activity when participants made correct negative responses
      relative to when they made correct positive responses. No areas activated
      significantly more for the positive responses than for the negative responses. It
      is suggested that the multiple frontal areas involved in the test phase of this
      task may reflect several component processes that underlie more general frontal
      functions.

PMID- 14642466
TI  - Neural correlates of the prolonged salience of painful stimulation.
AB  - Pain is a unique class of sensory experience from the perspective of salience.
      Nonpainful somatosensory stimuli usually require behavioral relevance or
      voluntary attention to maintain salience. In contrast, painful stimuli tend to
      have sustained salience even without explicit behavioral relevance or voluntary
      attention. We have previously identified a frontal-parietal-cingulate network of
      regions responding transiently to nonpainful sensory events. This network is
      sensitive to the task relevance and novelty of sensory events and likely
      represents the salience of events in the sensory environment. Since pain can
      remain salient for a prolonged period, we hypothesized that this network should
      show transient responses to the onset or offset of a nonpainful stimulus, but
      sustained responses throughout the duration of a painful stimulus. To test this
      hypothesis, we used functional MRI to examine the response of these regions to
      sustained (60-s) periods of painful and nonpainful transcutaneous electrical
      nerve stimulation. As predicted, the temporoparietal, inferior frontal, and
      anterior cingulate cortex showed only transient responses to the onset or offset
      of nonpainful stimulation, but a sustained response throughout the duration of
      painful stimulation. These regions therefore show tonic responses to stimuli with
      tonic salience, supporting a general role for these areas in representing
      stimulus salience. The thalamus and putamen also responded tonically throughout
      painful but not nonpainful stimulation. Previous studies have implicated the
      basal ganglia in supporting voluntary sustained attention. Our findings suggest
      that the basal ganglia may play a more general role in supporting sustained
      salience, whether through voluntary or involuntary mechanisms.

PMID- 14642467
TI  - LORETA imaging of P300 in schizophrenia with individual MRI and 128-channel EEG.
AB  - We investigated the characteristics of P300 generators in schizophrenics by using
      voxel-based statistical parametric mapping of current density images. P300
      generators, produced by a rare target tone of 1500 Hz (15%) under a frequent
      nontarget tone of 1000 Hz (85%), were measured in 20 right-handed schizophrenics
      and 21 controls. Low-resolution electromagnetic tomography (LORETA), using a
      realistic head model of the boundary element method based on individual MRI, was
      applied to the 128-channel EEG. Three-dimensional current density images were
      reconstructed from the LORETA intensity maps that covered the whole cortical gray
      matter. Spatial normalization and intensity normalization of the smoothed current
      density images were used to reduce anatomical variance and subject-specific
      global activity and statistical parametric mapping (SPM) was applied for the
      statistical analysis. We found that the sources of P300 were consistently
      localized at the left superior parietal area in normal subjects, while those of
      schizophrenics were diversely distributed. Upon statistical comparison,
      schizophrenics, with globally reduced current densities, showed a significant
      P300 current density reduction in the left medial temporal area and in the left
      inferior parietal area, while both left prefrontal and right orbitofrontal areas
      were relatively activated. The left parietotemporal area was found to correlate
      negatively with Positive and Negative Syndrome Scale total scores of
      schizophrenic patients. In conclusion, the reduced and increased areas of current
      density in schizophrenic patients suggest that the medial temporal and frontal
      areas contribute to the pathophysiology of schizophrenia, the frontotemporal
      circuitry abnormality.

PMID- 14642468
TI  - Reliability of functional localization using fMRI.
AB  - Neuroimaging researchers increasingly take advantage of the known functional
      properties of brain regions to localize them and probe changes in their activity
      under different conditions. The utility of this approach depends in part on the
      reliability of the methods used to define these regions of interest. Two
      operations may affect the reliability of functionally identified regions:
      spatially normalizing data to a stereotactic atlas and statistically combining
      data across participants to form a composite region (as opposed to identifying
      individual regions for each participant). The effect of these two operations on
      reliability was evaluated for two functionally identifiable regions: the MT
      complex and the frontal eye fields. Spatial normalization had almost no effect on
      within-subject reliability, while grouping across participants negatively
      affected retest measures of the activation and location of regions defined on
      separate occasions. We conclude that, for typical sample sizes and numbers of
      observations per subject, functional localization is most reliable when performed
      for each individual using data in atlas space.

PMID- 14642469
TI  - The functional neuroanatomy of visual conjunction search: a parametric fMRI
      study.
AB  - Visual conjunction search is proposed to be a multicomponent process which
      involves scaling and successive shifts of attention in space as well as object
      identification. Here, we first mapped brain areas sustaining the proposed
      attentional subprocesses and then tested whether their activity was modulated by
      search load, i.e., the number of shifts, as predicted by serial search models.
      Search load was manipulated indirectly by precueing a varying number of locations
      at which relevant objects were shown. Multiple subregions within the
      intraparietal sulcus (IPS) and the prefrontal cortex were activated after cueing.
      Activity in the right posterior IPS was modulated by the distance of attention
      shifts and in the left posterior IPS by "zooming out" to cover a large region of
      the visual field. More anterior subregions of the left IPS responded to object
      identification irrespective of the need for serial scanning. Corresponding
      regions in the right IPS were modulated parametrically with respect to search
      load, along with the right temporoparietal junction. These results support a
      functional segregation of subregions of the IPS. The posterior regions
      participate in large-scale shifts and scaling of the attentional focus and the
      anterior regions in object identification and rapid serial shifts during search.
      The sustained activation in the frontal eye fields after cueing suggests a role
      in maintaining attention in the periphery. Together with the findings in early
      visual areas from this experiment (Muller et al., 2003) the current observations
      are best accounted for by hybrid models of visual conjunction search, where
      parallel processing in visual and temporoparietal regions and serial scanning
      controlled by the right IPS cooperate.

PMID- 14642470
TI  - In vivo tracing of major rat brain pathways using manganese-enhanced magnetic
      resonance imaging and three-dimensional digital atlasing.
AB  - The magnetic resonance imaging (MRI)-detectable T1 contrast agent manganese
      (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and
      monkeys. We have tested to what extent this in vivo method is useful for three
      dimensional (3-D) survey of connectivity patterns in the rat somatosensory
      system. A commonly available 3 T human clinical MRI scanner was used to trace
      neural pathways following focal injection of manganese chloride (MnCl2) in the
      somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant
      signal enhancement in major projection systems, including corticocortical,
      corticostriatal, corticothalamic, corticotectal, corticopontine, and
      corticospinal pathways. To facilitate the assignment of anatomic localization to
      the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D
      digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison
      using the digital model allowed demonstration of a corticothalamic 3-D
      topographic organization in agreement with previously published two-dimensional
      topographic schemes based on classical neural tracing data. We conclude that
      anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization
      across multiple brain regions. The method allows a higher data throughput for 3-D
      studies of large-scale brain connectivity than conventional methods based on
      tissue sectioning.

PMID- 14642471
TI  - White matter fiber tracking in patients with space-occupying lesions of the
      brain: a new technique for neurosurgical planning?
AB  - The technique of fiber tracking based on diffusion tensor imaging offers the
      unique possibility of localizing the white matter pathways of the brain in vivo.
      In patients with cerebral tumors or space-occupying lesions of the brain, these
      pathways are often damaged or significantly displaced. Knowledge of the exact
      location of the lesion with respect to clinically eloquent white matter pathways
      is of great value to the neurosurgeon in planning the appropriate surgical
      strategy. We present here preliminary findings using the fiber tracking technique
      in four patients with space-occupying lesions and discuss the potential and
      limitations of the technique for lesion localization and neurosurgical planning.

PMID- 14642472
TI  - Early lateralization and orientation tuning for face, word, and object processing
      in the visual cortex.
AB  - Event-related potential (ERP) studies of the human brain have shown that object
      categories can be reliably distinguished as early as 130-170 ms on the surface of
      occipito-temporal cortex, peaking at the level of the N170 component. Consistent
      with this finding, neuropsychological and neuroimaging studies suggest major
      functional distinctions within the human object recognition system, particularly
      in hemispheric advantage, between the processing of words (left), faces (right),
      and objects (bilateral). Given these observations, our aim was to (1)
      characterize the differential response properties of the N170 to pictures of
      faces, objects, and words across hemispheres; and (2) test whether an effect of
      inversion for highly familiar and monooriented nonface stimuli such as printed
      words can be observed at the level of the N170. Scalp EEG (53 channels) was
      recorded in 15 subjects performing an orientation decision task with pictures of
      faces, words, and cars presented upright or inverted. All three categories
      elicited at the same latency a robust N170 component associated with a positive
      counterpart at centro-frontal sites (vertex-positive potential, VPP). While there
      were minor amplitude differences at the level of the occipital medial P1 between
      linguistic and nonlinguistic categories, scalp topographies and source analyses
      indicated strong hemispheric and orientation effects starting at the level of the
      N170, which was right lateralized for faces, smaller and bilateral for cars, and
      as large for printed words in the left hemisphere as for faces. The entire
      N170/VPP complex was accounted for by two dipolar sources located in the lateral
      inferior occipital cortex/posterior fusiform gyrus. These two locations were
      roughly equivalent across conditions but differed in strength and lateralization.
      Inversion delayed the N170 (and VPP) response for all categories, with an
      increasing delay for cars, words, and faces, respectively, as suggested by source
      modeling analysis. Such results show that early processes in object recognition
      respond to category-specific visual information, and are associated with strong
      lateralization and orientation bias.

PMID- 14642473
TI  - Functional topography of the secondary somatosensory cortex for nonpainful and
      painful stimuli: an fMRI study.
AB  - The regional activity of the contralateral primary (SI) and the bilateral
      secondary (SII) somatosensory areas during median nerve stimulations at five
      intensity levels (ranging from nonpainful motor threshold to moderate pain) was
      studied by means of functional magnetic resonance imaging (fMRI). The aim was to
      characterize the functional topography of SII compared to SI as a function of the
      stimulus intensity. Results showed that the galvanic stimulation of the median
      nerve activated the contralateral SI at all stimulus intensities. When considered
      as a single region, SII was more strongly activated in the contralateral than in
      the ipsilateral hemisphere. When a finer spatial analysis of the SII responses
      was performed, the activity for the painful stimulation was localized more
      posteriorly compared to that for the nonpainful stimulation. This is the first
      report on such a SII segregation for transient galvanic stimulations. The
      activity (relative signal intensity) of this posterior area increased with the
      increase of the stimulus intensity. These results suggest a spatial segregation
      of the neural populations that process signals conveyed by dorsal column-medial
      lemniscus (nonpainful signals) and neospinothalamic (painful signals) pathways.
      Further fMRI experiments should evaluate the functional properties of these two
      SII subregions during tasks involving sensorimotor integration, learning, and
      memory demands.

PMID- 14642475
TI  - Dynamic functional changes associated with cognitive skill learning of an adapted
      version of the Tower of London task.
AB  - In this study, we used a modified version of the Tower of London (TOL) planning
      task, in conjunction with positron emission tomography, to examine the neural
      substrates mediating cognitive skill learning. Twelve healthy, right-handed
      participants solved a total of 90 different TOL problems. They were scanned on
      four occasions during the fast learning stage as well as in a condition designed
      to control for internally guided movements. Practice of the TOL task resulted in
      a significant decrease in planning, execution, and total time taken to solve the
      problems. Consistent with the results of previous studies, early performance of
      the TOL task was associated with increased blood flow activity in the
      dorsolateral prefrontal, orbitofrontal, and parietal cortices on the left, as
      well as in the caudate nucleus, cerebellum, and premotor cortex, bilaterally.
      Interestingly, however, activity in the left caudate nucleus was maintained from
      the beginning to the end of the learning process, suggesting that this structure
      plays a role in this type of cognitive skill learning. In addition, correlational
      analyses revealed that improved performance on the TOL task was associated with a
      significant decrease of activity in the medial orbitofrontal and frontopolar
      cortices over the course of learning, areas thought to be involved in decision
      making, guessing, and monitoring of feedback information. In sum, the results
      lend further support to the idea that the learning of cognitive skills requiring
      planning and working memory capacities is mediated through a fronto-striatal
      network.

PMID- 14642474
TI  - Three-dimensional anatomical characterization of the developing mouse brain by
      diffusion tensor microimaging.
AB  - Investigation of three-dimensional (3D) morphometry of developing brains has been
      hindered by a lack of imaging modalities that can monitor the 3D evolution of
      various anatomical structures without sectioning and staining processes. In this
      study, we combined magnetic resonance microimaging and diffusion tensor imaging
      techniques to accomplish such visualization. The application of this approach to
      developing mouse embryos revealed that it could clearly delineate early critical
      structures such as neuroepithelium, cortical plate, and various axonal
      structures, and follow their developmental evolution. The technique was applied
      to the study of the Netrin-1 mutant, allowing verification of its anatomical
      phenotype.

PMID- 14642476
TI  - Latency (in)sensitive ICA. Group independent component analysis of fMRI data in
      the temporal frequency domain.
AB  - Independent component analysis (ICA), a data-driven approach utilizing high-order
      statistical moments to find maximally independent sources, has found fruitful
      application in functional magnetic resonance imaging (fMRI). A limitation of the
      standard fMRI ICA model is that a given component's time course is required to
      have the same delay at every voxel. As spatially varying delays (SVDs) may be
      found in fMRI data, using an ICA model with a fixed temporal delay for each
      source will have two implications. Larger SVDs can result in the splitting of
      regions with different delays into different components. Second, smaller SVDs can
      result in a biased ICA amplitude estimate due to only a slight delay difference.
      We propose a straightforward approach for incorporating this prior temporal
      information and removing the limitation of a fixed source delay by performing ICA
      on the amplitude spectrum of the original fMRI data (thus removing latency
      information). A latency map is then estimated for each component using the
      resulting component images and the raw data. We show that voxels with similar
      time courses, but different delays, are grouped into the same component.
      Additionally, when using traditional ICA, the amplitudes of motor areas are
      diminished due to systematic delay differences between visual and motor areas.
      The amplitudes are more accurately estimated when using a latency-insensitive ICA
      approach. The resulting time courses, the component maps, and the latency maps
      may prove useful as an addition to the collection of methods for fMRI data
      analysis.

PMID- 14642477
TI  - Identifying regional activity associated with temporally separated components of
      working memory using event-related functional MRI.
AB  - This study describes the neural circuitry underlying temporally separated
      components of working memory (WM) performance-stimulus encoding, maintenance of
      information during a delay, and the response to a probe. While other studies have
      applied event-related fMRI to separate epochs of WM tasks, this study differs in
      that it employs a methodology that does not make any a priori assumptions about
      the shape of the hemodynamic response (HDR). This is important because no one
      model of the HDR is valid across the range of activated brain regions and
      stimulus types. Systematic modeling inaccuracies may lead to the misattribution
      of activity to adjacent events. Twelve healthy subjects performed a numerical
      version of the Sternberg Item Recognition Paradigm adapted for rapid presentation
      event-related fMRI. This paradigm emphasized maintenance rather than manipulative
      WM processes and used a subcapacity WM load. WM trials with different delay
      lengths were compared to fixation. The HDR of the entire WM trial for each trial
      type was estimated using a finite impulse response (FIR). Regional activity
      associated with the Encode, Delay, and Probe epochs was identified using
      contrasts that were based on the FIR estimates and by examining the HDRs. Each
      epoch was associated with a distinct but overlapping pattern of regional
      activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal
      ganglia was exclusively associated with the probe. This suggests that
      frontostriatal neural circuitry participates in selecting an appropriate response
      based on the contents of WM.

PMID- 14642478
TI  - Subthreshold high-frequency TMS of human primary motor cortex modulates
      interconnected frontal motor areas as detected by interleaved fMRI-TMS.
AB  - To elucidate changes in human brain activity evoked by repetitive transcranial
      magnetic stimulation (rTMS), sub- and suprathreshold rTMS (4 Hz, 10 s) over the
      left primary sensorimotor cortex (M1/S1) was interleaved with blood-oxygenation
      level-dependent (BOLD) echo-planar imaging of primary and secondary motor areas.
      Suprathreshold rTMS over left M1/S1 caused marked increases in BOLD signal in the
      stimulated area and SMA-proper in seven of eight subjects. By contrast, we found
      no change in BOLD signal in the stimulated M1/S1, when rTMS was given at
      intensities that were subthreshold for inducing motor responses in the
      contralateral hand. However, five of eight subjects showed consistent increases
      in BOLD MRI signal in the SMA-proper and, to a lesser extent, in bilateral
      lateral premotor cortex (LPMC) during subthreshold rTMS. A decrease in BOLD MRI
      signal was found in contralateral (right) M1/S1 in 6/8 subjects across all
      conditions. No significant changes were observed in the pre-SMA. The results
      support the notion that BOLD MRI responses to suprathreshold rTMS over M1/S1 are
      dominated by neuronal activity related to reafferent processing of TMS-induced
      hand movements. At subthreshold intensity, a short train of high-frequency rTMS
      seems to predominantly modulate activity of corticocortical connections which
      link the stimulated area with remote frontal premotor areas.

PMID- 14642479
TI  - Additional neuromagnetic source activity outside the auditory cortex in duration
      discrimination correlates with behavioural ability.
AB  - In magneto- and electroencephalographic experiments on an oddball paradigm we
      compared the components of the auditory evoked fields and potentials of "attend"
      with "nonattend" conditions in 17 subjects. The former consisted of the
      performance of a duration discrimination task, where we observed augmented
      activity for the auditory sustained response. A multiple source analysis showed
      this effect mainly stemming from a third source outside the auditory cortices.
      The dipole moment of this specific activation was increased by 150% under the
      attend condition. Having anatomical 3D MRI data sets of 12 subjects the likely
      location of the third source was shown to be within the area of the precuneus or
      the posterior cingulate gyrus, which, along with its waveform, suggests it to be
      a CNV equivalent. Further, the dipole moment is correlated significantly to the
      subjects' psychometrically derived discriminative abilities.

PMID- 14642480
TI  - "Gating" effects of simultaneous peripheral electrical stimulations on human
      secondary somatosensory cortex: a whole-head MEG study.
AB  - The secondary somatosensory cortex (SII) is strongly involved in the processing
      of somatosensory tactile and nociceptive sensations. We investigated the effect
      on SII responses of simultaneous painful and nonpainful electrical stimulations
      delivered to the thumb and little finger. According to the "bimodal" (i.e.,
      nociceptive, tactile) organization of SII, it was expected that simultaneous
      painful and nonpainful stimulations would lead to modality interference with a
      marked reduction ("gating") of somatosensory evoked fields (SEFs) generated in
      SII. Eight different stimulus conditions were studied. Two conditions were
      simultaneous "unimodal" (thumb and little finger nonpainful; thumb and little
      finger painful) and two conditions were simultaneous "bimodal" (thumb nonpainful
      and little finger painful; thumb painful and little finger nonpainful). As a
      reference, four conditions included stimulations at single sites (thumb
      nonpainful, little finger nonpainful, thumb painful, little finger painful). The
      gating phenomenon was defined as the percentage of difference between the
      intensities of SII activation after simultaneous compared to the sum of the
      separate stimulations. Results showed that simultaneous stimulations induced
      gating effects on SEFs generated by SII. No significant gating differences were
      observed after the two unimodal stimulations, suggesting a negligible effect of
      global energy on gating. Instead, the gating effects on bilateral SII activity
      were stronger after simultaneous bimodal when compared to unimodal stimulations.
      Our findings hint that there could be a greater level of integration/convergence
      of painful and nonpainful stimuli in SII with respect to SI. Future studies
      should explore if it could have an important role in exploring pain relief.

PMID- 14642481
TI  - Diffusion tensor imaging detects and differentiates axon and myelin degeneration
      in mouse optic nerve after retinal ischemia.
AB  - Both axon and myelin degeneration have significant impact on the long-term
      disability of patients with white matter disorder. However, the clinical
      manifestations of the neurological dysfunction caused by white matter disorders
      are not sufficient to determine the origin of neurological deficits. A
      noninvasive biological marker capable of detecting and differentiating axon and
      myelin degeneration would be a significant addition to currently available tools.
      Directional diffusivities derived from diffusion tensor imaging (DTI) have been
      previously proposed by this group as potential biological markers to detect and
      differentiate axon and myelin degeneration. To further test the hypothesis that
      axial (lambdaparallel) and radial (lambdaperpendicular) diffusivities reflect
      axon and myelin pathologies, respectively, the optic nerve was examined serially
      using DTI in a mouse model of retinal ischemia. A significant decrease of
      lambdaparallel, the putative DTI axonal marker, was observed 3 days after
      ischemia without concurrently detectable changes in lambdaperpendicular, the
      putative myelin marker. This result is consistent with histological findings of
      significant axonal degeneration with no detectable demyelination at 3 days after
      ischemia. The elevation of lambdaperpendicular observed 5 days after ischemia is
      consistent with histological findings of myelin degeneration at this time. These
      results support the hypothesis that lambdaparallel and lambdaperpendicular hold
      promise as specific markers of axonal and myelin injury, respectively, and,
      further, that the coexistence of axonal and myelin degeneration does not confound
      this utility.

PMID- 14642482
TI  - Relation of cognitive reserve and task performance to expression of regional
      covariance networks in an event-related fMRI study of nonverbal memory.
AB  - Cognitive reserve (CR) has been established as a mechanism that can explain
      individual differences in the clinical manifestation of neural changes associated
      with aging or neurodegenerative diseases. CR may represent individual differences
      in how tasks are processed (i.e., differences in the component processes), or in
      the underlying neural circuitry (of the component processes). CR may be a
      function of innate differences or differential life experiences. To investigate
      to what extent CR can account for individual differences in brain activation and
      task performance, we used fMRI to image healthy young individuals while
      performing a nonverbal memory task. We used IQ estimates as a proxy for CR.
      During both study and test phase of the task, we identified regional covariance
      patterns whose change in subject expression across two task conditions correlated
      with performance and CR. Common brain regions in both activation patterns were
      suggestive of a brain network previously found to underlie overt and covert
      shifts of spatial attention. After partialing out the influence of task
      performance variables, this network still showed an association with the CR,
      i.e., there were reserve-related physiological differences that presumably would
      persist were there no subject differences in task performance. This suggests that
      this network may represent a neural correlate of CR.

PMID- 14642483
TI  - Neural substrates participating in acquisition of facial familiarity: an fMRI
      study.
AB  - The amygdala is related to recognition of faces and emotions, and functional
      magnetic resonance imaging (fMRI) studies have reported that the amygdala is
      habituated over time with repetition of facial stimuli. When subjects are
      presented repeatedly with unfamiliar faces, they come to gradually recognize the
      unfamiliar faces as familiar. To investigate the brain areas participating in the
      acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted
      an fMRI study in 16 healthy subjects. During the task periods, the subjects were
      instructed to see presented unfamiliar faces repeatedly and to judge whether the
      face was male or female or whether the face had emotional valences. The
      experiment consisted of nine sessions. To clarify the brain areas that showed
      increasing or decreasing activation as the experimental session proceeded, we
      analyzed the fMRI data using specified linear covariates in the face recognition
      task from the first session to the ninth session. Imaging data were investigated
      on a voxel-by-voxel basis for single-group analysis according to the random
      effect model using Statistical Parametric Mapping. The bilateral posterior
      cingulate cortices showed significant increases in activity as the experimental
      sessions proceeded, while the activation in the right amygdala and the left
      medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an
      important role in the acquisition of facial familiarity.

PMID- 14642484
TI  - A neural mass model for MEG/EEG: coupling and neuronal dynamics.
AB  - Although MEG/EEG signals are highly variable, systematic changes in distinct
      frequency bands are commonly encountered. These frequency-specific changes
      represent robust neural correlates of cognitive or perceptual processes (for
      example, alpha rhythms emerge on closing the eyes). However, their functional
      significance remains a matter of debate. Some of the mechanisms that generate
      these signals are known at the cellular level and rest on a balance of excitatory
      and inhibitory interactions within and between populations of neurons. The
      kinetics of the ensuing population dynamics determine the frequency of
      oscillations. In this work we extended the classical nonlinear lumped-parameter
      model of alpha rhythms, initially developed by Lopes da Silva and colleagues
      [Kybernetik 15 (1974) 27], to generate more complex dynamics. We show that the
      whole spectrum of MEG/EEG signals can be reproduced within the oscillatory regime
      of this model by simply changing the population kinetics. We used the model to
      examine the influence of coupling strength and propagation delay on the rhythms
      generated by coupled cortical areas. The main findings were that (1) coupling
      induces phase-locked activity, with a phase shift of 0 or pi when the coupling is
      bidirectional, and (2) both coupling and propagation delay are critical
      determinants of the MEG/EEG spectrum. In forthcoming articles, we will use this
      model to (1) estimate how neuronal interactions are expressed in MEG/EEG
      oscillations and establish the construct validity of various indices of nonlinear
      coupling, and (2) generate event-related transients to derive physiologically
      informed basis functions for statistical modelling of average evoked responses.

PMID- 14642485
TI  - Stimulus symmetry affects the bisection of figures but not lines: evidence from
      event-related fMRI.
AB  - Many geometric shapes retain their symmetry when bisected, but appear
      asymmetrical when misbisected. We have previously shown that this correspondence
      can guide the accuracy and speed of perceptual bisection (Landmark) judgments.
      Using event-related fMRI, here we examined whether the behavioural effects of
      symmetry are also evident at the neural level. The data showed that the
      presence/absence of symmetry modulates the activity of right anterior cingulate
      gyrus, an area associated with a variety of higher level attentional functions. A
      previous visual half-field study also showed that bisected lines are apprehended
      more quickly and accurately than misbisected lines in right, but not left, visual
      field. We were able to localise this advantage to right superior temporal gyrus.
      Significantly, we found no evidence that symmetry played a role in apprehending
      the midpoint of the line stimuli traditionally used to assess visual neglect. The
      data clarify the effects of visual symmetry on bisection behaviour, and highlight
      novel dissociations within the neural systems thought to underline Landmark
      performance.

PMID- 14642486
TI  - Is the brain cortex a fractal?
AB  - The notion of fractal has been largely used to describe geometrical properties of
      complex objects in biology and medicine. In the present study the question is
      addressed whether the human cerebral cortex is self-similar in a statistical
      sense, which is commonly referred to as being a fractal. A new calculational
      method is presented, which is volumetric and based on the fast Fourier transform
      (FFT) of segmented three-dimensional high-resolution magnetic resonance images.
      The analysis covers a wide range of spatial scales from the size of the whole
      cortex to the ultimate pixel size. Results obtained in six subjects confirm the
      fractal nature of the human cerebral cortex down to a spatial scale of 3 mm. The
      obtained fractal dimension is D = 2.80 +/- 0.05, which is in reasonable agreement
      with previously reported results. Deployment of FFT enables a simple
      interpretation of the results and yields a high performance, which is necessary
      to analyze the entire cortex. Thus the FFT-based analysis of segmented MR images
      offers a comprehensive approach to study neurodevelopmental and neurodegenerative
      changes in the fractal geometry of the cerebral cortex.

PMID- 14642487
TI  - Quantitative assessment of P-glycoprotein function in the rat blood-brain barrier
      by distribution volume of [11C]verapamil measured with PET.
AB  - The blood-brain barrier (BBB) is a functional barrier that hampers the delivery
      of various drugs to the brain by its physicoanatomical properties and by the
      presence of ATP-driven drug efflux pumps, such as P-glycoprotein (P-gp). The aims
      of this study were (1) to study whether the distribution volume (DV) is useful
      for quantification of (labeled) P-gp substrate kinetics over the BBB and (2) to
      study how brain DV is affected by P-gp modulation. We measured the kinetics of
      the P-gp substrate [11C]verapamil (0.1 mg/kg) in rat brains using positron
      emission tomography (PET) and arterial blood sampling. Cyclosporin A (CsA) at 0,
      10, 15, 25, 35, and 50 mg/kg of body weight was used as a P-gp modulator. The
      [11C]verapamil kinetics were very well described by DV, computed by
      noncompartmental Logan analysis. Logan analysis resulted in excellent fits of
      dynamic PET data, revealing the reversible behavior of [11C]verapamil and its
      associated DV. The DV in unmodulated rats was 0.65 ml/ml +/- 0.23 (mean +/- SD).
      After modulation with 10, 15, 25, 35, and 50 mg/kg of CsA, DV values increased to
      0.82 +/- 0.06, 1.04 +/- 0.20, 2.85 +/- 0.51, 2.91 +/- 0.64, and 3.77 +/- 1.23,
      respectively. The [11C]Verapamil kinetics were saturable at modulation levels
      above 25 mg/kg of CsA. The data fitted well by a four-parameter Hill plot (R2 =
      0.79). In conclusion, the DV of [11C]verapamil is a valid and potent tool to
      measure the kinetics of (labeled) P-gp substrates in vivo at the BBB. The brain
      DV of [11C]verapamil increases dose dependently by P-gp modulation. Quantitative
      insight into in vivo P-gp modulation may be a promising step toward assessment of
      P-gp substrate delivery to human brains.

PMID- 14642488
TI  - Binaural specialisation in human auditory cortex: an fMRI investigation of
      interaural correlation sensitivity.
AB  - A listener's sensitivity to the interaural correlation (IAC) of sound plays an
      important role in several phenomena in binaural hearing. Although IAC has been
      examined humans, little is known about the neural basis of sensitivity to IAC in
      humans. The present study employed functional magnetic resonance imaging to
      measure blood oxygen level-dependent (BOLD) activity in auditory brainstem and
      cortical structures in human listeners during presentation of band-pass noise
      stimuli between which IAC was varied systematically. The stimuli evoked
      significant bilateral activation in the inferior colliculus, medial geniculate
      body, and auditory cortex. There was a significant positive relationship between
      BOLD activity and IAC which was confined to a distinct subregion of primary
      auditory cortex located bilaterally at the lateral extent of Heschl's gyrus.
      Comparison with published anatomical data indicated that this area may also be
      cytoarchitecturally distinct. Larger differences in activation were found between
      levels of IAC near unity than between levels near zero. This response pattern is
      qualitatively compatible with previous measures of psychophysical and
      neurophysiological sensitivity to IAC. extensively in neurophysiological studies
      in animals and in psychophysical studies in

PMID- 14642489
TI  - Instruction-specific brain activations during episodic encoding. a generalized
      level of processing effect.
AB  - In a within-subject design we investigated the levels-of-processing (LOP) effect
      using visual material in a behavioral and a corresponding PET study. In the
      behavioral study we characterize a generalized LOP effect, using pleasantness and
      graphical quality judgments in the encoding situation, with two types of visual
      material, figurative and nonfigurative line drawings. In the PET study we
      investigate the related pattern of brain activations along these two dimensions.
      The behavioral results indicate that instruction and material contribute
      independently to the level of recognition performance. Therefore the LOP effect
      appears to stem both from the relative relevance of the stimuli (encoding
      opportunity) and an altered processing of stimuli brought about by the explicit
      instruction (encoding mode). In the PET study, encoding of visual material under
      the pleasantness (deep) instruction yielded left lateralized frontoparietal and
      anterior temporal activations while surface-based perceptually oriented
      processing (shallow instruction) yielded right lateralized frontoparietal,
      posterior temporal, and occipitotemporal activations. The result that deep
      encoding was related to the left prefrontal cortex while shallow encoding was
      related to the right prefrontal cortex, holding the material constant, is not
      consistent with the HERA model. In addition, we suggest that the anterior medial
      superior frontal region is related to aspects of self-referential semantic
      processing and that the inferior parts of the anterior cingulate as well as the
      medial orbitofrontal cortex is related to affective processing, in this case
      pleasantness evaluation of the stimuli regardless of explicit semantic content.
      Finally, the left medial temporal lobe appears more actively engaged by elaborate
      meaning-based processing and the complex response pattern observed in different
      subregions of the MTL lends support to the suggestion that this region is
      functionally segregated.

PMID- 14642490
TI  - Interactive specification of regions of interest on brain surfaces.
AB  - We describe Surface Editor-a tool for interactive specification of regions of
      interest (ROIs) on brain surfaces. The tool allows users to define subsurfaces by
      tracing around areas within a triangle-mesh brain surface. The input to the
      program is a triangle-mesh representation of a brain volume and a set of user
      defined input points on the mesh. The program connects each pair of successive
      input points with a polyline that results from the intersection of the mesh with
      a plane that is approximately normal to the mesh. The polyline comprises coplanar
      line segments. The boundary of an ROI is a connected set of polylines that
      intersects triangle edges to form a continuous path. To validate Surface Editor
      we demonstrated that the program could be used to interactively delineate gyri on
      brain surfaces, and we showed that paths that the program generated were
      comparable to paths that a user generated and to shortest paths.

PMID- 14642491
TI  - The musician's brain: functional imaging of amateurs and professionals during
      performance and imagery.
AB  - We compared activation maps of professional and amateur violinists during actual
      and imagined performance of Mozart's violin concerto in G major (KV216).
      Execution and imagination of (left hand) fingering movements of the first 16 bars
      of the concerto were performed. Electromyography (EMG) feedback was used during
      imagery training to avoid actual movement execution and EMG recording was
      employed during the scanning of both executed and imagined musical performances.
      We observed that professional musicians generated higher EMG amplitudes during
      movement execution and showed focused cerebral activations in the contralateral
      primary sensorimotor cortex, the bilateral superior parietal lobes, and the
      ipsilateral anterior cerebellar hemisphere. The finding that professionals
      exhibited higher activity of the right primary auditory cortex during execution
      may reflect an increased strength of audio-motor associative connectivity. It
      appears that during execution of musical sequences in professionals, a higher
      economy of motor areas frees resources for increased connectivity between the
      finger sequences and auditory as well as somatosensory loops, which may account
      for the superior musical performance. Professionals also demonstrated more
      focused activation patterns during imagined musical performance. However, the
      auditory-motor loop was not involved during imagined performances in either
      musician group. It seems that the motor and auditory systems are coactivated as a
      consequence of musical training but only if one system (motor or auditory)
      becomes activated by actual movement execution or live musical auditory stimuli.

PMID- 14642492
TI  - Gating of somatosensory evoked magnetic fields during the preparatory period of
      self-initiated finger movement.
AB  - The temporal change in somatosensory evoked magnetic fields (SEFs) in the
      preparatory period of self-initiated voluntary movement was investigated. The SEF
      following stimulation of the right median nerve was recorded, using a 204-channel
      whole-head MEG system, in nine healthy subjects during a self-initiated extension
      of the right index finger every 5 to 7 s. The preparatory period before finger
      movement was divided into six subperiods, and the MEG signals following the
      stimulation in each subperiod were averaged separately. SEFs were also recorded
      in the resting state. The ECD strengths for N20m and P60m were not significantly
      changed in any subperiod before movement compared with those in the resting
      state. The ECD strength for P30m was significantly smaller 500 ms or less before
      movement than during the resting state and 1,500 ms or less before movement
      compared to that during the period from 3,000 to 4,000 ms before movement. Thus,
      we confirmed that the SEF components were attenuated even during a period of self
      initiated voluntary movement. The modulation started at least 1,500 ms before
      movement and was greater for the P30m than the N20m component. These findings
      suggested that motor-associated cortices attenuated SEF components by a
      centrifugal gating process.

PMID- 14642493
TI  - Auditory-evoked magnetic field codes place of articulation in timing and
      topography around 100 milliseconds post syllable onset.
AB  - This study demonstrates by means of magnetic source imaging how consonants and
      vowels that constitute a syllable differently affect the neural processing within
      the auditory cortex. We recently identified a topographically separate processing
      for mutually exclusive place features in isolated vowels (Obleser et al., in
      press). Does this mapping principle also hold for stop consonants with differing
      places of articulation? How is the N100m response to consonant-vowel (CV)
      syllables affected by the congruency of place information in the consonant and
      the vowel? Moreover, how is the N100m affected by coarticulation, i.e., the
      spreading of place features to adjacent phonemes? By systematically varying
      phonological information in the consonant as well as in the vowel of CV
      syllables, we were able to reveal a difference in N100m syllable source location
      along the anterior-posterior axis due to mutually exclusive places of
      articulation in the vowel of the syllable. We also found a change in source
      orientation rather than source location due to the same mutually exclusive
      features in the onset of the syllable. Furthermore, the N100m time course of the
      brain response delivered important complementary information to identify the
      phonological features present in the speech signal. Responses to all syllable
      categories originated in the perisylvian region anterior to the source of a band
      passed noise stimulus. The systematic variation of both consonantal and vocalic
      place features and the study of their interaction on auditory processing proves
      to be a valuable method to gain more insight into the elusive phenomenon of human
      speech recognition.

PMID- 14642494
TI  - Assessment of the impact of model-based scatter correction on [18F]-FDG 3D brain
      PET in healthy subjects using statistical parametric mapping.
AB  - It is recognized that scatter correction can supply more accurate absolute
      quantification, and that iterative reconstruction results in better noise
      properties and significantly reduces streak artefacts; however, it is not
      entirely clear whether they produce significant changes in [18F]-FDG distribution
      of reconstructed 3D brain PET images relative to not scatter corrected images and
      analytic reconstruction procedures. The current study assesses the effect of
      model-based scatter correction using the single-scatter simulation algorithm and
      iterative reconstruction in 3D brain PET studies, using statistical parametric
      mapping (SPM) analysis. The study population consisted of 14 healthy volunteers
      (6 males, 8 females; age 63-80 years). PET images were reconstructed using an
      analytic 3DRP reprojection algorithm with (SC) and without explicit scatter
      correction (NSC), as well as using an iterative ordered subset-expectation
      maximization (OSEM) algorithm. Calculated attenuation correction was performed
      assuming uniform attenuation (mu = 0.096 cm(-1)) for brain tissues when data are
      precorrected for scatter. The broad-beam attenuation coefficient (mu = 0.06 cm(
      1)) determined from phantom studies was applied to NSC images. The images were
      coregistered and normalized using the default [15O]-H2O template supplied with
      SPM99 and an [18F]-FDG template. A t statistic image for the contrast condition
      effect was then constructed. The contrast comparing SC to NSC images suggest that
      regional brain metabolic activity decreases significantly in the frontal gyri, in
      addition to the middle temporal and postcentral gyri. On the other hand, activity
      increases in the cerebellum, thalamus, insula, brainstem, temporal lobe, and the
      frontal cortex. No significant changes were detected when comparing images
      reconstructed using analytic and iterative algorithms. It is concluded that, for
      some cerebral areas, significant differences in [18F]-FDG distribution arise when
      images are reconstructed with and without explicit SC. This needs to be
      considered when interpreting [18F]-FDG 3D brain PET images after applying SC.

PMID- 14642495
TI  - Optical imaging of the retinotopic organization of V1 in the common marmoset.
AB  - We examined the retinotopic mapping of the visual world in the primary visual
      cortex of the marmoset monkey using differential optical imaging. Two sets of
      complementary stripe-like locations were visually stimulated in turn. Their
      difference depicts the cortical representations of continuous bands of visual
      space. By rotating the sets of stripe-like locations it is possible to map
      different spatial axes. Analogous to the macaque we found that the V1/V2 border
      represented the vertical meridian, while horizontal, 45-, and 135-degree angled
      stripes of space were also represented in a continuous manner. We developed a new
      automatic method of calculating local measures of cortical magnification from our
      optical retinotopic maps. Using this method we found no evidence of any local
      anisotropies in cortical representation. Overall our results indicate that space
      is mapped isotropically in the primary visual cortex of the common marmoset.

PMID- 14642496
TI  - Automated method for extracting response latencies of subject vocalizations in
      event-related fMRI experiments.
AB  - For functional magnetic resonance imaging studies of the neural substrates of
      language, the ability to have subjects performing overt verbal responses while in
      the scanner environment is important for several reasons. Most directly, overt
      responses allow the investigator to measure the accuracy and reaction time of the
      behavior. One problem, however, is that magnetic resonance gradient noise
      obscures the audio recordings made of voice responses, making it difficult to
      discern subject responses and to calculate reaction times. ASSERT (Adaptive
      Spectral Subtraction for Extracting Response Times), an algorithm for removing MR
      gradient noise from audio recordings of subject responses, is described here. The
      signal processing improves intelligibility of the responses and also allows
      automated extraction of reaction times. The ASSERT-derived response times were
      comparable to manually measured times with a mean difference of -8.75 ms
      (standard deviation of difference = 26.2 ms). These results support the use of
      ASSERT for the purpose of extracting response latencies and scoring overt verbal
      responses.

PMID- 14642497
TI  - Activation of cortical areas in music execution and imagining: a high-resolution
      EEG study.
AB  - Neuroimaging studies have shown that execution of a musical sequence on an
      instrument activates bilateral frontal opercular regions, in addition to
      bilateral sensorimotor and supplementary motor areas. During imagining activation
      of the same areas without primary sensorimotor areas was shown. We recorded EEG
      from 58 scalp positions to investigate the temporal sequence and the time course
      of activation of these areas while violin players prepared to execute, executed,
      prepared to imagine, or imagined a musical sequence on a violin. During the
      preparation for the sequence in three of seven musicians investigated the
      bilateral frontal opercular regions became active earlier than the motor areas
      and in one of them simultaneously with the motor areas. In two of the musicians a
      rather variable pattern of activation was observed. The frontal opercular regions
      were also strongly involved throughout the period of music execution or
      imagining. The supplementary motor area was involved in both preparation for the
      sequence and during execution and imagining of the sequence. The left primary
      sensorimotor area was involved in the preparation and termination of the musical
      sequence for both execution and imagining. The right sensorimotor area was
      strongly involved in the preparation for and during the execution of the
      sequence. We conclude that the bilateral frontal opercular regions are crucial in
      both preparation for and during music execution and imagining. They may have
      "mirror neurone" properties that underlie observation or imagining of one's own
      performance. The motor areas are differentially activated during the preparation
      and execution or imagining the sequence.

PMID- 14642498
TI  - Hemodynamic responses in visual, motor, and somatosensory cortices in
      schizophrenia.
AB  - Recent advances in functional neuroimaging allow comparisons between individuals
      with schizophrenia and control groups. Previous studies of schizophrenia have
      used blocked task paradigms and, more recently, "rapid event-related" designs in
      which stimuli of different types are presented close together in an intermixed
      fashion. The validity of between-group comparisons in both of these types of
      paradigms depends on excluding the possibility that observed functional response
      differences are attributable to altered hemodynamic responses in individuals with
      schizophrenia. The goal of the current study was to begin a systematic
      examination of the hemodynamic response in schizophrenia. We administered a
      flashing checkerboard paradigm with a motor response to 17 individuals with
      schizophrenia and 24 healthy controls. Both groups showed robust activation of
      visual, motor, somatosensory, and supplementary motor regions. For the most part,
      the individuals with schizophrenia demonstrated intact peak amplitude, variance,
      latency, and linear summation properties in regions activated by this task. We
      did find some evidence for increased variability in the amplitude and latency of
      the hemodynamic responses in the visual and somatosensory cortices, although the
      magnitudes of these group differences were relatively small. These results begin
      to validate the interpretation of functional neuroimaging studies of
      schizophrenia in terms of neuronal as opposed to vascular mechanisms.

PMID- 14642499
TI  - Resting-state brain glucose utilization as measured by PET is directly related to
      regional synaptophysin levels: a study in baboons.
AB  - It is classically recognized that regional cerebral glucose consumption (CMRglc),
      as measured by positron emission tomography (PET) and [18F]-2-fluorodeoxyglucose
      (FDG), is a precise index of the integrated local neuronal activity. However,
      despite extensive use of the FDG-PET method, the significance of the measured
      CMRglc has been little addressed so far. In the present study, we aimed for the
      first time to test whether resting-state CMRglc is directly related to synaptic
      density. To this end, we investigated in the baboon the relationships between
      CMR(glc) and the levels of synaptophysin (SY), a presynaptic protein classically
      used to assess synaptic density. CMR(glc), measured in vivo by FDG-PET at the
      resting-state, and SY levels, assessed postmortem by the Western blot technique,
      were quantified in seven brain areas of five baboons. By applying these two
      techniques to the same animals, we found significant positive correlations
      between CMR(glc) and SY levels, across all regions and all animals, as well as
      within individual baboons. These findings strongly support the hypothesis that
      resting-state CMR(glc) reflects integrated synaptic activity.

PMID- 14642500
TI  - MRI correlates of pathology in parkinsonism: segmented inversion recovery ratio
      imaging (SIRRIM).
AB  - The two commonest, clinically well-defined, forms of parkinsonism are idiopathic
      Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Both involve,
      inter alia, pathological changes in the substantia nigra pars compacta (SN(C)).
      In PD there is neuronal loss with associated Lewy body pathology and microglial
      activation. Three morphological features have been identified [Brain 114 (1991),
      2283; Greenfield's Neuropathology 2 (1997), 289]. First, there is a gradient of
      pathological change such that the lateral segments are more affected than the
      medial. Second, there is thinning of the pigmented tissue, and third, there is a
      broadening of the overall structure in a dorsal-ventral direction, possibly
      caused by the migration of melanin-laden macrophages [Greenfield's Neuropathology
      2 (1997), 289]. In contrast, PSP is characterized pathologically by intraneuronal
      neurofibrillary tangles. There are two morphological features in the SN(C) [Brain
      114 (1991), 2283]. First, the gradient of pathological change is in the opposite
      direction to that of PD (i.e., the medial segments are more affected than the
      lateral). Second, there is atrophy. Any technique sensitive to neuropathology
      should be capable of detecting these features. We have previously reported on a
      new approach to detecting signal change in the substantia nigra in PD. This makes
      use of a ratio of images acquired by two distinct inversion recovery sequences
      [J. Neurol, Neurosurg. Psychiatry 67 (1999), 815; Am. J. Neuroradiol. 21 (2000)
      697]. The prior work suggests that the technique is sensitive to, but not
      necessarily specific for, PD. We present here a preliminary report on an
      extension of the work. This is a semiautomated segmentation analysis that enables
      the substantia nigra to be displayed as an isolated structure. The technique is
      now given the acronym SIRRIM (segmented inversion recovery ratio imaging). In
      contrast to our earlier work, it allows for a more accurate assessment of the
      gross abnormalities. We report typical SIRRIM images of the SN(C). Images are
      shown for three subjects: a normal control, a patient with PD, and a "disease
      control" (a patient with PSP). In these examples all three morphological features
      of PD, as well as both morphological features of PSP, have radiological
      correlates. These preliminary findings suggest that SIRRIM may be specific for
      both diseases.

PMID- 14642502
TI  - Diagnosis of compressive neuropathies in patients with fibromyalgia.
AB  - The hand surgeon relies on the Tinel sign in the physical examination of the
      patient suspected of having a peripheral nerve entrapment. Fibromyalgia is
      recognized by the American College of Rheumatology as a condition characterized
      by having tender points on physical examination. This article reviews the
      location of the 9 bilateral critical diagnostic fibromyalgia points as they
      relate to known sites of anatomic entrapment of peripheral nerves in the upper
      extremity. The interpretation of this article is that the Tinel sign may be used
      with validity to identify the site of a peripheral nerve compression in the upper
      extremity in the patient with fibromyalgia.

PMID- 14642503
TI  - Impact of impaired wrist motion on hand and upper-extremity performance(1).
AB  - PURPOSE: To quantify and compare the disabilities caused by reduced and absent
      wrist motion using objective measurements of task performance and perceived
      disability, and to assess the compensatory motions of the shoulder, elbow,
      forearm, and trunk caused by impaired wrist motion. METHODS: A clinical study of
      21 normal subjects was done to measure physical performance and to assess wrist
      function under conditions of reduced (30 degrees flexion and 30 degrees
      extension) and nearly absent wrist motion using established physical tests and
      questionnaires (Disabilities of the Arm, Shoulder, and Hand [DASH], Patient Rated
      Wrist Evaluation [PRWE], and a study-specific survey). The clinical study also
      measured compensatory motions of the shoulder, elbow, forearm, and trunk.
      RESULTS: Average times to perform the Jebsen test and activities of daily living
      (ADLs) test increased for both motion-restricted conditions of the wrist but did
      not differ significantly between the conditions. Questionnaire scores regarding
      function were significantly worse for both motion-restricted conditions and
      poorest for nearly absent motion. Average compensatory motions in the extremity
      and trunk statistically increased for both motion-restricted conditions but were
      not marked and did not differ between the conditions. High variability among
      subjects occurred in all physical tests and questionnaires for both motion
      restricted conditions. CONCLUSIONS: Perceived disability from reduced wrist
      motion appeared greater than measured functional loss using common physical tests
      and outcome surveys.

PMID- 14642504
TI  - Management of the scaphoid during four-corner fusion-a cadaveric study.
AB  - PURPOSE: To examine the effects of scaphoid retention, inclusion, and excision on
      wrist motion and radiolunate contact characteristics in a cadaveric model after
      simulated 4-corner fusion with rigid internal fixation. METHODS: Seven fresh
      frozen cadaveric upper extremities were examined. For all surgical manipulations
      the motion was measured and contact characteristics were assessed using ultra-low
      prescale pressure-sensitive film. RESULTS: Compared with the intact specimen,
      simple 4-corner fusion with scaphoid retention led to a significant decrease in
      extension, radial deviation, and ulnar deviation, but no change in radiolunate
      contact characteristics. After 4-corner fusion there was no significant
      difference in motion or radiolunate contact characteristics between scaphoid
      retention and scaphoid inclusion. After 4-corner fusion scaphoid excision allowed
      significantly greater radial deviation compared with scaphoid retention and
      scaphoid inclusion. Compared with the intact specimen 4-corner fusion with
      scaphoid excision also led to a significant increase in radiolunate contact area
      and mean contact pressure. CONCLUSIONS: When performing 4-corner arthrodesis in
      the absence of radioscaphoid arthritis, scaphoid excision may improve motion at
      the cost of increased mean radiolunate contact pressure.

PMID- 14642505
TI  - Surgical outcome of radial osteotomy for Kienbock's disease-minimum 10 years of
      follow-up.
AB  - PURPOSE: Long-term results of radial osteotomy for Kienbock's disease seldom are
      seen in the literature. The purpose of this study was to report the minimum 10
      year results and to compare them with the 5-year results to determine whether the
      favorable intermediate-term results were maintained. METHODS: Twenty-five
      patients who underwent radial osteotomy were followed-up for a mean period of
      14.5 years. They were examined for pain, grip strength, and wrist range of motion
      (ROM). Through a review of clinical records, 5-year postoperative results were
      collected. The carpal height ratio and Stahl's index were measured and the x-rays
      were inspected for osteoarthritic changes. We devised an original lunate grade to
      evaluate radiologic improvement of the ischemic lunate. Overall results were
      evaluated using Cooney's wrist function score and Nakamura's scoring system for
      Kienbock's disease. The long-term results were compared with both the
      preoperative status and the 5-year results. RESULTS: Pain, ROM, and grip strength
      were improved significantly after surgery, and the results were maintained for a
      long period. Carpal height ratio and Stahl's index did not show significant
      improvements but ischemic lunate showed certain radiologic improvements with time
      by the lunate grade system. Osteoarthritic changes were observed in 54% of
      patients at 5 years and in 73% of patients at the final follow-up evaluation, but
      the arthrosis generally was mild and did not affect the clinical results.
      Cooney's wrist function score was excellent or good in 96% of the patients, and
      the results with Nakamura's scoring system for Kienbock's disease were excellent
      or good in 68% of the patients at the final follow-up evaluation. The percentages
      were the same 5 years after surgery. CONCLUSIONS: Radial osteotomy for Kienbock's
      disease is a reasonable treatment option and clinical improvement lasts for a
      long period of time. Although radiologic improvement was not drastic, the inner
      structure such as sclerotic change or bone cysts of the lunate improved with
      time, indicating healing of the ischemic lunate. Severe osteoarthritic change or
      proximal migration of the capitate can be avoided.

PMID- 14642506
TI  - Results of the cemented SR trapeziometacarpal prosthesis in the treatment of
      thumb carpometacarpal osteoarthritis.
AB  - PURPOSE: The purpose of this study was to analyze our experience in the treatment
      of trapeziometacarpal (TMC) osteoarthritis with a cemented surface replacement
      arthroplasty. METHODS: We did a retrospective study of 19 patients with 20 hands
      operated on with this technique, with a follow-up evaluation of 33 months. We
      analyzed the preoperative stage, the postoperative clinical results, measured the
      radiographic changes found at the end of the study, and correlated all these data
      with a statistical study. For statistical analysis chi(2) test and Student t-test
      were used. The level of significance was set at a p value of.05 or less. RESULTS:
      With an average follow-up period of 33 months (range, 24-45 mo) the following
      rates were obtained: 55% loosenings and 15% ankylosis owing to periprosthetic
      calcifications (70% of failures of the technique). Four patients (20%) needed a
      revision surgery (a salvage procedure with a dynamic ligament reconstruction
      arthroplasty). In the subjective functional evaluation only 8 cases of 19
      patients (40%) maintained an excellent/good result at the end of the study.
      CONCLUSIONS: In our group of patients the cemented surface replacement TMC
      prosthesis was not an adequate surgical option for the treatment of TMC
      osteoarthritis. Further studies are necessary to clarify the role of this
      surgical technique in this pathology.

PMID- 14642507
TI  - Carpal bone postures and motions are abnormal in both wrists of patients with
      unilateral scapholunate interosseous ligament tears.
AB  - PURPOSE: The recent ability to measure 3-dimensional in vivo carpal kinematics
      has facilitated the noninvasive study of complex carpal bone motion. METHODS: In
      this study we examined the flexion/extension carpal kinematics of both wrists in
      8 patients with unilateral scapholunate interosseous ligament (SLIL) tears by
      using computed tomographic (CT) imaging and a markerless bone registration
      technique. Carpal bone neutral posture and flexion/extension motion of both
      wrists of the injured patients were compared with the same parameters in wrists
      of 10 uninjured male and female volunteers (normals). RESULTS: The neutral
      posture of the injured scaphoid and lunate were significantly more extended than
      those of normals. In these patients, however, the postures of the scaphoid and
      lunate in the contralateral uninjured wrists also were abnormal and were similar
      to those of the injured wrist. In addition, extension of the lunate and flexion
      of the scaphoid in both the injured and uninjured wrist were significantly
      different from normal but not different from each other. CONCLUSIONS: This study
      was unable to attribute altered carpal posture and motion to SLIL tears because
      abnormalities were found in both wrists of patients with unilateral injury. The
      etiology of abnormal wrist kinematics in the asymptomatic wrist of patients with
      unilateral tears of the scapholunate ligament is not known.

PMID- 14642508
TI  - Assessment of midcarpal deformity of the wrist using the triangulation method.
AB  - PURPOSE: The purpose of this study is to present an alternative method for static
      radiologic assessment of the wrist for midcarpal instability (ie, palmar
      intercalated segmental instability [PISI] and dorsal intercalated segmental
      instability [DISI]). The triangulation method uses 3 anatomic landmarks observed
      on the standard lateral x-ray of the wrist. METHODS: A total of 125 normal
      lateral radiographs were measured to determine the normal range for the dorsal
      limb (DL) to palmar limb (PL) ratio. A 2-step process of performing triangulation
      is described. The first step is nonspecific screening of the radiograph and
      defines values greater than 1.0 as having a DISI deformity and values less than
      0.5 as having a PISI deformity. The second step is used only for borderline
      values, which takes the position of the wrist into consideration and uses a
      normagram (reference chart) to match the DL:PL ratio with the radiometacarpal
      (RM) angle. RESULTS: The average lateral wrist position was 8.4 degrees of
      extension (-8.4). The average DL:PL ratio was 0.75 +/- 0.09 (range, 0.93-0.57).
      CONCLUSIONS: Based on these data we defined DISI deformity of the wrist as DL:PL
      ratios greater than 1.0, and ratios less than 0.5 representing PISI deformities.
      The triangulation method of assessing midcarpal alignment of the carpus is a
      practical and simple alternative to the traditional static radiologic method of
      assessing midcarpal instability of the wrist.

PMID- 14642509
TI  - Influence of the pronator quadratus and supinator muscle load on DRUJ stability.
AB  - PURPOSE: To determine the effects of altering the load contributions of the
      pronator quadratus and supinator muscles on in vitro distal radioulnar joint
      (DRUJ) stability during pronation and supination and before and after ulnar head
      excision. METHODS: Multiple pronation trials were conducted with incremental
      loading of the pronator quadratus relative to the pronator teres muscle;
      supination trials were similarly conducted with incremental loading of the
      supinator relative to the biceps muscle. All trials were conducted using an upper
      limb apparatus capable of simulating muscle/tendon loading and displacement.
      Stability measurements included dorsal-volar translations of the radius relative
      to the ulna and DRUJ diastasis and convergence. RESULTS: Increased pronator
      quadratus loading did not affect intact DRUJ stability but effects were noted
      after ulnar head excision when the forearm was positioned between neutral and
      full pronation. Incremental loading of the supinator muscle did not modify DRUJ
      stability in the intact or ulnar head excised state. CONCLUSIONS: Pronator
      quadratus muscle activity aggravates forearm instability after ulnar head
      excision. Immobilization of the forearm in mid- to full supination should
      minimize pronator quadratus activity and optimize soft-tissue healing. This
      information may be useful to develop in vitro muscle-loading scenarios and
      analytical forearm models.

PMID- 14642510
TI  - Computer-assisted distal radius osteotomy.
AB  - PURPOSE: To establish the accuracy, precision, and clinical feasibility of a
      novel technique of computer-assisted distal radius osteotomy for the correction
      of symptomatic distal radius malunion. METHODS: Six patients underwent a computer
      assisted distal radius osteotomy and were followed-up for an average of 25
      months. Objective radiographic measurements and functional outcomes, as measured
      by clinical examination including grip strength and range of motion, and
      Disability of the Arm, Shoulder and Hand (DASH) questionnaires, were used.
      RESULTS: The mean radiographic parameters included an increase of radial
      inclination to 21 degrees from 12 degrees (normal, 23 degrees ). Dorsal and volar
      tilt (malunion) were corrected to 9 degrees from -30 degrees and 21 degrees,
      respectively (normal, 10 degrees ). Ulnar variance was corrected to 1.9 mm from
      7.5 mm (normal, +1.5 mm). Normal is defined as the average of the contralateral
      limb radiographs. The mean clinical outcome measures at an average of 25 months
      included a DASH global score of 14, a DASH individual item average score of 1.6,
      and an average affected side grip strength of 79% when compared with the
      unaffected side. CONCLUSIONS: The results of the computer-assisted technique were
      comparable with published results of traditional non-computer-assisted opening
      wedge osteotomy techniques. This technique allows a surgeon to accurately and
      precisely recognize and correct 3-dimensional deformities of the distal radius
      including axial malalignment (supination). The technique has the added benefit of
      reducing radiation exposure to the patient and surgical team because fluoroscopy
      is not used during the procedure. Additional benefits of the computer-assisted
      technique include the ability to perform multiple surgical simulations to
      optimize the alignment plan, and it serves as an excellent teaching tool for less
      experienced surgeons.

PMID- 14642511
TI  - A biomechanical evaluation of lateral plating of distal radial shaft fractures.
AB  - PURPOSE: In this ex vivo biomechanical study we compared the maximum
      anterior/posterior bending moment, maximum torque, torsional stiffness, and twist
      angle at failure of distal radial shaft (Galeazzi) fractures stabilized with
      lateral plating (LP) and anterior plating (AP) and subjected to 4-point
      anterior/posterior bending and torsion. METHODS: Simulated fractures (oblique
      osteotomy between the middle and distal thirds of each radius) were created in 21
      pairs of fresh, unembalmed, cadaver radii. One radius from each pair was
      stabilized with AP (n = 21); the contralateral radius was stabilized with LP (n =
      21). Eleven pairs of specimens were tested to failure in torsion; the remaining
      10 pairs were tested to failure in 4-point anterior/posterior bending.
      Differences between plating groups were checked for significance using paired t
      tests. RESULTS: AP fixation was stronger in torsion (12.8 +/- 5.6 N-m) and
      anterior/posterior bending (40.1 +/- 25.7 N-m) than LP fixation (10.7 +/- 5.6 N-m
      and 36.0 +/- 30.5 N-m, respectively), although the differences were not
      significant. Similarly there was no significant difference in twist angle at
      failure (29 degrees +/- 13 degrees vs 23 degrees +/- 10 degrees ) or in torsional
      stiffness (0.6 +/- 0.2 N-m/ degrees vs 0. 6 +/- 0.2 N-m/ degrees ) between AP and
      LP fixations, respectively. CONCLUSIONS: Because LP fixation was not mechanically
      superior to AP fixation and required additional tendon elevation and dissection
      of the dorsal sensory nerve and possibly of the lateral antebrachial cutaneous
      nerves, AP fixation appears to be the preferable treatment for Galeazzi
      fractures.

PMID- 14642512
TI  - Prospective evaluation of biceps to triceps and deltoid to triceps for elbow
      extension in tetraplegia.
AB  - PURPOSE: The purpose of this study was to evaluate and compare the deltoid to
      triceps and biceps to triceps transfers for restoration of elbow extension in
      young persons with tetraplegia. METHODS: This was a prospective randomized study.
      Sixteen arms of 9 subjects between 8 and 20 years of age with cervical-level
      spinal cord injuries were assigned randomly to undergo either a deltoid to
      triceps transfer or a biceps to triceps transfer. All arms were followed-up
      prospectively for at least 2 years after surgery. RESULTS: Elbow extension was
      restored in 8 arms via the deltoid and in 8 arms via the biceps transfers. At the
      24-month follow-up evaluation 7 of the 8 biceps transfers produced antigravity
      strength (grade 3 or better); in contrast only one arm with the deltoid transfer
      was able to extend against gravity. There was a considerable but subclinical loss
      (no subject appreciated any functional deficit) of elbow flexion torque after
      both transfers. Three months after surgery the deltoid group showed a 51% loss of
      elbow flexion torque and the biceps group showed a 52% loss of elbow flexion
      torque. By 24 months after surgery both groups improved but still showed a loss
      of flexion torque (deltoid 32%, biceps 47%). After gaining elbow extension the
      subjects in both groups rated the performance of most activities of daily living
      (ADL) and all self-selected activities as better, as measured on the Modified
      University of Minnesota Tendon Transfer Functional Improvement Questionnaire and
      the Canadian Occupational Performance Measure, respectively. Likewise all
      subjects were more satisfied with performance of their goals after undergoing
      elbow extension reconstruction. CONCLUSIONS: This study showed the benefits of
      restoring elbow extension in persons with tetraplegia and provided support for
      the biceps transfer as an alternative to the deltoid to triceps transfer in
      individuals with good brachialis and supinator strength.

PMID- 14642513
TI  - The noncircular shape of the radial head.
AB  - PURPOSE: The purpose of this study was to define the shape of the radial head by
      identifying the relationship between precisely defined axes of the radial head.
      METHODS: An anatomic study was done to define the shape of the radial head and
      specifically the relationship between the long and the short axis. Twenty-seven
      cadaveric upper extremities were used. The x and y axes of the radial head were
      defined in relationship to the radial notch of the ulna, with the forearm in
      neutral position. Outer diameters of the x and y axis were measured. These were
      compared with the actual maximum and minimum diameters of the radial head. X and
      y diameters of the articulating surface of the radial head also were measured.
      RESULTS: Paired 1-tailed Student's t-tests were used to compare the x and y
      diameters of the radial head. Regression analysis of x and y diameters of the
      radial head was done to identify a correlation between these parameters.Paired 1
      tailed Student's t-tests showed a significant difference between X and Y
      diameters of the radial head. Regression analysis of x and y diameters of the
      radial head showed a strong correlation between these 2 axes. CONCLUSIONS: The
      radial head is not round. A strong correlation exists between the x and y
      diameters of the radial head. The orientation of the long axis is perpendicular
      to the radial notch with the forearm in neutral rotation. This finding will make
      it possible to approach the anatomy of the radial head more closely when
      designing radial head prostheses. The definition of the axes can be used as a
      guide when implanting the radial head prosthesis.

PMID- 14642514
TI  - Biomechanics of the Steindler flexorplasty surgery: a computer simulation study.
AB  - PURPOSE: Our goal was to investigate the capacity of a Steindler flexorplasty to
      restore elbow flexion to persons with C5-C6 brachial plexus palsy. In this
      procedure the origin of the flexor-pronator mass is moved proximally onto the
      humeral shaft. We examined how the choice of the proximal attachment site for the
      flexor-pronator mass affects elbow flexion restoration, especially considering
      possible side effects including limited wrist and forearm motion owing to passive
      restraint from stretched muscles. METHODS: A computer model of the upper
      extremity was used to simulate the biomechanical consequences of various surgical
      alterations. Unimpaired, preoperative, and postoperative conditions were
      simulated. Seven possible transfer locations were used to investigate the effects
      of choice of transfer location. RESULTS: Each transfer site produced a large
      increase in elbow flexion strength. Transfer to more proximal attachment sites
      also produced large increases in passive resistance to wrist extension and
      forearm supination. CONCLUSIONS: To reduce detrimental side effects while
      achieving clinical goals our theoretical analysis suggests a transfer to the
      distal limit of the traditional transfer region.

PMID- 14642515
TI  - Synovial sheath cell migratory response to flexor tendon injury: an experimental
      study in rats.
AB  - PURPOSE: We aimed to investigate the degree of participation of synovial sheath
      cells in the process of tendon healing by selective cell labeling and direct
      observation of migrational pathways. METHODS: We designed a novel rat animal
      model that employed vital dye staining of synovial sheath cells. The flexor
      digitorum profundus (FDP) tendon was removed from its sheath and vital dye was
      applied directly to the synovial sheath cells. A window was cut in the removed
      tendon before being returned to the sheath, thus placing a tendon injury adjacent
      to the labeled synovial sheath cells. The synovium remained intact at all times,
      and labeling was confirmed to be localized to the synovium. The migrational
      response of the synovial sheath cells to the tendon injury was observed by
      harvesting the tendons at 1, 3, 5, and 7 days (n = 6 for each time period) after
      injury and assessing tendon response with frozen sections under ultraviolet
      microscopy. RESULTS: Labeled synovial sheath cells were observed within the
      substance of the healing tendon 24 hours after injury, with numbers increasing
      with time for up to 5 days, but decreasing by day 7. CONCLUSIONS: This study
      confirms that in the rat model synovial sheath cells move into the healing tendon
      area and then migrate into the tendon core.

PMID- 14642516
TI  - Effects of superficialis tendon repairs on lacerated profundus tendons within or
      proximal to the A2 pulley: an in vivo study in chickens.
AB  - PURPOSE: In a flexor tendon injury model in chickens we undertook a study to
      evaluate effects of the flexor digitorum superficialis (FDS) tendon repairs on
      excursions, work of flexion, and adhesions of the repaired flexor digitorum
      profundus (FDP) tendon after their injuries within or proximal to the equivalent
      of the A2 pulley and early tendon motion. METHODS: Thirty-five leghorn chickens
      were divided into 3 groups. In group 1 the FDS and FDP tendons of the long toes
      on both sides were transected in the area covered by the pulley. In group 2 the
      tendons were transected proximal to the pulley. In the first 2 groups, both
      tendons were repaired on the left feet, and only the profundus was repaired with
      superficialis excision on the right. The operated toes underwent simulated
      passive flexion for 3 weeks and results were evaluated 8 weeks after surgery.
      Chickens in group 3 were unoperated and served as the controls. RESULTS: When the
      tendons were cut within the pulley the FDP excursions and work of flexion were
      significantly better in the toes in which the FDS was excised than in those with
      both tendon repairs. When they were cut proximal to the pulley the repairs of
      both tendons had outcomes similar to that with excision of the FDS. Adhesions
      were more severe when both tendons were repaired under the pulley as compared
      with those after repair of a single tendon. CONCLUSIONS: This study showed
      different effects of the surgical repair or excision of the FDS on the FDP tendon
      within or proximal to a major pulley. Repair of both tendons worsens the gliding
      of the FDP tendon and increases adhesions within the major pulley; however,
      repair of both tendons yields outcomes equivalent to that after repair of only
      the FDP tendon proximal to the pulley.

PMID- 14642517
TI  - Tendon transfers for thumb opposition: a biomechanical study of pulley location
      and two insertion sites.
AB  - PURPOSE: The purpose of this biomechanical study was to test 5 proximal tendon
      pulley sites or routes of tendon transfer and 2 distal tendon insertion sites
      that are used commonly for performing a thumb opposition transfer. METHODS: Five
      fresh-frozen cadaver arms were used to test (1) an around flexor carpi ulnaris
      (FCU) pulley, (2) an FCU loop pulley, (3) a Guyon's canal pulley, (4) a junction
      of the distal edge of the transverse carpal ligament and the ulnar border of the
      palmar aponeurosis (Royle-Thompson pulley), and (5) a palmar thenar subcutaneous
      transfer (Camitz). Two tendon insertion sites were tested: a palmar radial
      insertion into the abductor pollicis brevis and a dorsal ulnar insertion into the
      thumb proximal phalanx. RESULTS: The Guyon's canal and Royle-Thompson pulleys
      produced the greatest amount of approximation of the thumb pulp to the fifth
      metacarpal head. The around the FCU pulley, FCU loop pulley, and Camitz transfer
      produced the greatest palmar abduction. The Guyon's canal and Royle-Thompson
      pulleys were the most mechanically efficient pulleys, producing the least amount
      of transmitted force. The palmar radial insertion site produced better thumb
      opposition, metacarpophalangeal joint abduction, metacarpophalangeal joint
      flexion, and approximation of the thumb pulp to the fifth metacarpal head.
      CONCLUSIONS: We conclude that the choice of the proximal pulley used may depend
      on the needs of the transfer, and a palmar radial thumb insertion is more
      effective than the dorsal ulnar insertion.

PMID- 14642518
TI  - Ultrasound visualization of central slip injuries of the finger extensor
      mechanism.
AB  - PURPOSE: To evaluate the ability of ultrasound to detect a central tear of the
      finger extensor tendon mechanism. METHODS: Twelve fresh-frozen and thawed cadaver
      fingers were used. All fingers had a midradial incision with exposure of the
      extensor mechanism over the proximal interphalangeal joint. Six fingers had a
      sharp transection of the central slip. The other 6 fingers were used as sham
      dissection controls. All fingers had the exposure closed by suture and then were
      examined by a musculoskeletal ultrasonographer. RESULTS: All 12 fingers were
      identified correctly as either sham controls with intact central slips or as
      injury models that had a transected central slip. Thus there was a sensitivity of
      100% a specificity of 100%, and a positive predictive value of 1.000, which were
      statistically significant. CONCLUSIONS: Diagnostic ultrasound is a very accurate
      noninvasive study that can identify central slip injuries in the extensor
      mechanism of the finger. We recommend that clinically suspected cases of
      boutonniere injury be scanned by high-frequency ultrasound to confirm the
      diagnosis and allow either early initiation of splinting or eliminate the need
      for prolonged splinting required for this injury.

PMID- 14642519
TI  - Supernumerary extensor pollicis longus tendon: a case report.
AB  - We report a rare case in which the extensor pollicis longus (EPL) tendon was
      separated into 2 slips at the site of origin, ran an abnormal course across the
      wrist, and combined in the vicinity of the metacarpophalangeal (MCP) joint; the
      tendon on the radial side passed through another tendon sheath between the first
      and second compartments and the tendon on the ulnar side passed over the extensor
      retinaculum.

PMID- 14642520
TI  - Redefining the "Arcade of Struthers".
AB  - PURPOSE: To define the anatomy and presence of the arcade of Struthers, its
      anatomic variations, and potential sites of compression of the ulnar nerve.
      METHODS: In 11 fresh specimen dissections, the ulnar nerve was followed from the
      brachial plexus through the anterior compartment into the posterior compartment
      through the intermuscular septum and the arcade of Struthers on to the cubital
      tunnel. The arcade was identified, dissected, measured, and photographed. All
      anatomic variations were documented. RESULTS: The arcade of Struthers and
      intermuscular septum were present in all 11 specimens. The arcade was not merely
      an opening in the septum nor was it a short band as typically described: the
      arcade was better described as a fibrous canal with an average length of 5.7 cm.
      Its openings at either end were 3.9 and 9.6 cm proximal to the medial epicondyle.
      The structural components of the canal consisted of the fibrous tissue of the
      intermuscular septum, the internal brachial ligament, the deep fascia of the
      triceps, and the epimysium of the triceps muscle itself. The ulnar nerve was
      bound tightly within the entire canal in one case. In all specimens the nerve had
      an hourglass indentation at the proximal opening of the canal between the
      intermuscular septum and the internal brachial ligament. CONCLUSIONS: The arcade
      of Struthers consists of a fibrous canal. The tightest point is the proximal end
      of the canal at the intermuscular septum that represents the clinically relevant
      site of entrapment or compression of the ulnar nerve.

PMID- 14642521
TI  - Neuroma prevention by end-to-side neurorraphy: an experimental study in rats.
AB  - PURPOSE: The successful treatment of painful neuromas remains a difficult goal to
      attain. In this report we explore the feasibility of neuroma prevention by
      insertion of the proximal end of a nerve through an end-to-side neurorraphy into
      an adjacent mixed nerve to provide a pathway and target for axons deprived of
      their end organ. METHODS: Experiments were performed on a total of twenty 250-g
      Sprague-Dawley rats. Two groups of 10 animals were prepared. Group A served as an
      anatomic control. In group B the right saphenous nerve was transected and
      implanted end-to-side through an epineurial window into the tibial nerve distal
      to the trifurcation of the sciatic nerve. After 12 weeks the corresponding
      sensory neurons were identified by retrograde labeling techniques and
      histomorphometric analysis of the proximal and distal tibial nerve segments, and
      regular histology of the end-to-side site were performed. RESULTS: The results of
      the retrograde labeling of the corresponding sensory neuron pool of the saphenus
      nerve showed extensive labelling of the L1 to L3 spinal ganglions after
      intracutaneous tracer application of the planta pedis. The morphology of the end
      to-side coaptation site and histomorphologic analysis prove that sensory neurons
      penetrate the perineurial sheath and axons regenerate along the tibial Schwann
      cell tubes toward their targets. CONCLUSIONS: Axons of a severed peripheral nerve
      that are provided with a pathway and target through an end-to-side coaptation
      will either be pruned or establish some type of end-organ contact so that a
      neuroma can be prevented. Whether these axons will lead to disturbing sensations
      such as paresthesia or dysesthesia in the newly found environment or remain
      silent codwellers, this experiment cannot answer. Long-term results of future
      clinical work will have to decide whether the prevention of the neuroma through
      end-to-side coaptation will be an appropriate therapy for this difficult problem.

PMID- 14642522
TI  - Responsiveness of Dupuytren's disease fibroblasts to 5 alpha-dihydrotestosterone.
AB  - PURPOSE: We recently showed that androgen receptors are expressed in Dupuytren's
      contracture. The aim of the present work was to test the responsiveness of
      Dupuytren's fibroblasts to 5 alpha-dihydrotestosterone (5 alpha-DHT), the active
      form of testosterone. RESULTS: Cultured palmar fascia cells from 10 patients with
      Dupuytren's contracture and 4 normal subjects were exposed to 5 alpha-DHT (10 or
      100 ng/mL) for 1, 3, 7, and 15 days. Their phenotype was analyzed
      immunohistochemically for alpha-smooth muscle actin and androgen receptor
      expression and proliferation rates were studied. RESULTS: At 15 days the higher
      concentration of 5 alpha-DHT induced an increase in Dupuytren's fibroblast
      proliferation, whereas anti-alpha-smooth muscle actin exhibited the strongest
      expression. At the same time point androgen receptor expression decreased with
      the lower concentration and disappeared altogether with the higher dose of 5
      alpha-DHT. CONCLUSIONS: The palmar fascia is a target tissue for androgen action
      via androgen receptors. Further studies are required to determine whether control
      of androgen receptor may control the evolution of Dupuytren's disease.

PMID- 14642523
TI  - Anatomy and pathomechanics of ring and small finger carpometacarpal joint
      injuries.
AB  - PURPOSE: The purpose of this study was to detail the pathomechanics and
      pathoanatomy of fracture dislocations of the ring finger and small finger
      carpometacarpal (CMC) joint by duplicating the pathomechanics of the fist blow.
      METHODS: A custom-made jig was used to position 20 fresh-frozen cadaver upper
      extremities in forearm neutral rotation, 90 degrees of elbow flexion, 20 degrees
      of wrist extension, and 20 degrees and 30 degrees of flexion at the ring and
      small finger CMC joint, respectively. First 7.7 kg of weight were dropped from a
      height of 0.76 m to 1.1 m to axially load the ring and small metacarpal (MC)
      heads through a custom-made apparatus. Fluoroscopic examination before and after
      loading, and detailed dissection after loading, were used to identify any osseous
      and/or ligamentous injuries. RESULTS: The most common fractures were a dorsal
      capitate fracture and a middle MC dorsal base fracture. The most common
      combinations of fractures were the dorsal capitate and dorsal hamate fractures.
      Multiple fractures often were identified in a number of locations including
      dorsally: the capitate, hamate, and index through small metacarpal bases, and
      volarly: the hook of the hamate and the middle through the small MC bases.
      CONCLUSIONS: The patterns of injuries encountered at the ring and small CMC
      joints can be explained by the direction and force of the applied load, position
      of the CMC joint at the time of loading, and the constraints imposed by specific
      CMC ligaments. A detailed analysis of the fracture patterns and associated
      ligament anatomy suggests that the typical ring and small carpometacarpal
      fracture dislocations are a more complex combination of fractures than identified
      by plain radiographs alone. The complexity of these injuries is greater than
      previously recognized and is most likely the result of a combination of axial
      load and shear stresses resulting in carpal fractures and ligament avulsions as
      well as fracture dislocations. This study suggests that computed tomography may
      be the preferred diagnostic imaging method for complete assessment of these
      injuries.

PMID- 14642524
TI  - The biomechanical properties of the finger metacarpophalangeal joints to varus
      and valgus stress.
AB  - PURPOSE: The purpose of this study was to determine the normal biomechanical
      properties of the passive capsuloligamentous structures about the finger
      metacarpophalangeal (MCP) joints subjected to dynamic varus/valgus loading and to
      equate these findings to the clinical situation. METHODS: The finger MCP joints
      from 9 fresh-frozen cadaver hands were tested in a custom-designed testing
      apparatus that applied a varus/valgus force in each direction. Testing was
      performed at 0 degrees, 30 degrees, 60 degrees, and 90 degrees of MCP joint
      flexion. Load-displacement curves were generated for each specimen. A nonlinear
      hysteresis curve was apparent on loading and unloading. A region of collateral
      ligament laxity was identified whereby minimal torque (< 0.5 Nm) caused
      progressive joint angulation. Subsequently incremental load was required to
      produce further joint angulation. The slope of this region was used to calculate
      early and late collateral ligament stiffness. RESULTS: The index and long fingers
      showed a significant decrease in the region of collateral ligament laxity between
      0 degrees and 90 degrees. The long finger collateral ligament laxity also
      diminished significantly between 30 degrees and 90 degrees. The collateral
      ligament laxity did not significantly change in the ring and small digits
      throughout MCP joint flexion. The early or late phase of collateral ligament
      stiffness was not affected by the amount of MCP joint flexion across any of the
      digits, except in late radial collateral ligament stiffness of the long finger
      between 0 degrees and 60 degrees. CONCLUSIONS: The additional stability and
      clinical observation of tightening of the MCP in flexion appears related to the
      decreased laxity of the collateral ligaments and not to alterations in the
      biomechanical properties of the collateral ligaments.

PMID- 14642525
TI  - Enchondroma protuberans of the phalanx: a case report.
AB  - Enchondroma protuberans, which is defined as an exophytic enchondroma of a long
      bone, is a rare condition. There have been 6 previously reported cases with only
      1 case occurring in the hand. We report a case of an enchondroma protuberans of
      the ring finger middle phalanx treated by marginal excision of the soft-tissue
      component, intramedullary curettage, and placement of calcium phosphate cement.
      There was no evidence of local recurrence at the 1-year follow-up examination.

PMID- 14642526
TI  - Bcl-2 antisense oligodeoxynucleotide increases the sensitivity of leukemic cells
      to arsenic trioxide.
AB  - Cell culture, tissue chemistry and flow cytometry were used to determine whether
      antisense bcl-2 oligodeoxynucleotides enhanced the sensitivity of leukemia cells
      to arsenic trioxide. A combination of arsenic trioxide with antisense bcl-2
      oligodeoxynucleotides inhibited cell growth, induced apoptosis and induced bcl-2
      protein expression in K562 and NB4 leukemic cells more significantly than either
      arsenic trioxide or the oligodeoxynucleotides on their own (P<0.01). Thus, bcl-2
      antisense oligodeoxynucleotides increase the sensitivity of leukemic cells to
      arsenic trioxide. Combined use of the two agents could be a novel and attractive
      strategy in leukemia treatment.

PMID- 14642527
TI  - FasL-induced downregulation of CD28 expression on jurkat cells in vitro is
      associated with activation of caspases.
AB  - Ligation of CD28, which is present on the majority of CD4(+)T cells, promotes
      proliferation and immune responses. However, expression of CD28 declines with
      aging, and apoptosis may contribute to this decline. We have investigated the
      molecular mechanism underlying the decrease in CD28 expression in Jurkat T cells
      cultured with FasL. FasL blocks expression of CD28 at the transcriptional level.
      This correlates with activation of caspase cascades: active caspase-3 can be
      detected and inhibitors of caspase-3 and caspase-8 increase CD28 promoter
      activity and CD28 expression. These findings are consistent with the hypothesis
      that apoptosis plays a key role in the age-related decline of CD28 expression and
      hence in immunosenescence.

PMID- 14642528
TI  - Calcium ions as a factor of cell-cell cooperation in hepatocyte cultures.
AB  - Ultradian protein synthesis rhythm was used as a marker of cell cooperation in
      synchronous dense and non-synchronous sparse hepatocyte cultures. Phenylephrine
      (2 microM, 2 min), an alpha (1)-adrenoreceptor agonist, which exerts
      [Ca(2+)](cyt)elevation from intracellular stores, affected protein synthesis
      rhythm in sparse cultures, i.e. initiated cooperative activity of the cells. The
      same effect was produced by 2,5-di(tertiary-butyl)-1,4-benzohydroquinone (10
      microM, 2 min), which increases [Ca(2+)](cyt)by a non-receptor pathway.
      Pretreatment of dense cultures with the intracellular calcium chelator, 1,2-bis
      (2-aminophenoxy) ethane-N,N,N',N'- tetraacetic acid (acetoxymethyl) ester (BAPTA
      AM) at 10-20 microM for, 30-60 min resulted in loss of the rhythm of protein
      synthesis, i.e. loss of cooperative activity between the cells. The medium
      conditioned by control dense cultures initiated rhythm in sparse cultures,
      whereas the conditioned medium of cultures pretreated with BAPTA-AM did not.
      [Ca(2+)](cyt)increase is known to occur with monosialoganglioside GM1 treatment.
      By ELISA estimation, the GM1 content in 3 h conditioned medium was similar in
      control dense cultures to that in cultures pretreated with BAPTA-AM. Bearing in
      mind data on the Ca(2+)-dependence of vesicle formation and shedding, the
      conditioned medium was separated by 150000 g centrifugation to supernatant
      containing monomers and micelles, and a pellet containing vesicular form of
      gangliosides. Only the latter initiated cooperative activity of the cells of
      sparse cultures. These cultures were also synchronized by GM1-containing
      liposomes at lower concentrations than added free GM1, 0.0003 and 0.06 microM
      respectively. Thus, GM1 and calcium are both involved in cell-cell
      synchronization. Activation of gangliosides, including GM1 and elevation of
      [Ca(2+)](cyt,)is known to lead to changes of protein kinase activity and protein
      phosphorylation resulting in modulation of oscillations in protein metabolism.

PMID- 14642529
TI  - Involvement of myosin in intracellular motility and cytomorphogenesis in
      Micrasterias.
AB  - Myosin was detected on Western blots of Micrasterias denticulata extracts by use
      of antibodies from different sources. Inhibitors with different targets of the
      actomyosin system, such as the myosin ATPase-blockers N-ethylmaleimide (NEM) and
      2,3-butanedione monoxime (BDM), or the myosin light chain kinase inhibitor 1-(5
      iodonaphthalene-1-sulfonyl)-1H-hexhydro-1,4-diazapine (ML7), had similar effects
      on intracellular motility during cell development in the green alga Micrasterias,
      thus pointing towards a participation of myosin in these processes. The drugs
      markedly altered the mode of postmitotic nuclear migration, slowed down
      cytoplasmic streaming, changed cell pattern development and prevented normal
      chloroplast distribution and spreading into the growing semicell. In addition, an
      increase and dilatations in ER cisternae and marked morphological changes of the
      Golgi system were observed by transmission electron microscopy after exposure of
      growing cells to BDM. Neither BDM nor ML7 exhibited any effect on the
      distribution or arrangement of the cortical F-actin network nor on the F-actin
      basket around the nucleus, characteristic of untreated growing Micrasterias cells
      (J Cell Sci 107 (1994) 1929). This is particularly interesting since BDM caused
      disintegration of the microtubule system co-localized to the F-actin cage during
      normal nuclear migration. Together with the fact that other microtubules not
      connected to the F-actin system remained uninfluenced by BDM, this observation is
      evidence of an integrative function of myosin between the cytoskeleton elements.

PMID- 14642530
TI  - Impact of glafenine hydrochloride on human endothelial cells and human vascular
      smooth muscle cells: a substance reducing proliferation, migration and
      extracellular matrix synthesis.
AB  - The aim of this study was to examine the effects of glafenine hydrochloride (a
      nonsteroidal anti-inflammatory drug) on proliferation, clonogenic activity, cell
      cycle, migration, and the extracellular matrix protein tenascin of human aortic
      smooth muscle cells (haSMCs) and human endothelial cells (ECs) in vitro.HaSMCs
      and ECs were seeded in tissue culture flasks. The cells were treated for 4 days
      with glafenine hydrochloride (10 microM, 50 microM, 100 microM). Half of the
      treated groups were incubated again with glafenine hydrochloride, the other half
      received medium free of glafenine hydrochloride every 4 days until day 20. The
      growth kinetics and clonogenic activity were assessed. Cell cycle distribution
      was investigated by FACS, migratory ability was evaluated, and effects on
      extracellular matrix synthesis were assessed by immunofluorescence. Glafenine
      hydrochloride inhibited the proliferation and clonogenic activity of haSMCs and
      ECs in a dose-dependent manner. A block in the G2/M phase and a reduction in the
      G1 phase occurred. The migratory ability of haSMCs was impaired in a dose
      dependent manner and the extracellular matrix protein tenascin was reduced. As
      glafenine hydrochloride has the ability to fully inhibit proliferation and to
      partially inhibit migration in haSMCs, it could be an interesting substance for
      further research in the field of restenosis therapy.

PMID- 14642532
TI  - Syndecan-2 expression enhances adhesion and proliferation of stably transfected
      Swiss 3T3 cells.
AB  - Syndecans (heparan sulfate proteoglycans) participate in cell-cell and cell
      matrix adhesion and are co- and low-affinity receptors for growth factors and
      enzymes, respectively. We examined the influence of stable syndecan-2 expression
      in Swiss 3T3 cells on cell-adhesion and proliferation. Higher syndecan-2
      expression changed cell morphology and increased spreading and adhesion in these
      cells and proliferation induced by FCS and FGF-2. This emphasizes the role of
      syndecan-2 in the integration of signals from soluble and insoluble factors.

PMID- 14642531
TI  - Polarised secretion of cytokines in primary human microvascular endothelial cells
      is not dependent on N-linked glycosylation.
AB  - Human microvascular endothelial cells (HMVEC) grow in monolayers on Transwell
      filters and restrict permeability between the apical and basolateral media. We
      show that these cell monolayers are capable of sorting labelled endogenous
      proteins, including chemokines, growth factors and cytokines, to either the
      apical or basolateral media. IL-8 and GMCSF were secreted predominantly into the
      apical medium, whereas MIC-1 was secreted into the basolateral medium. This
      polarity did not correlate with glycosylation, as IL-8 and MIC-1 are both N
      glycosylated, but were sorted to opposite sides of the cell. IL-6 is not
      glycosylated and did not display significant polarity in secretion. Similarly,
      the polarity of secretion of endogenous glycoproteins was not related to their
      glycosylation.

PMID- 14642533
TI  - Upregulation of CYP2e1 and CYP3a activities in histamine-deficient histidine
      decarboxylase gene targeted mice.
AB  - Histamine is a biogenic amine with multiple physiological functions. Its
      importance in allergic inflammation is well characterized; moreover, it plays a
      role in the regulation of gastric acid production, various hypothalamic
      functions, such as food uptake, and enhancing TH2 balance during immune
      responses. Using histidine decarboxylase gene targeted (HDC(-/-)) BALB/c mice, we
      studied the effect of the absence of histamine on four cytochrome p450 enzyme
      activities. Their selective substrates were measured: ethoxyresorufin O
      dealkylase activity of CYP1A, pentoxyresorufin O-dealkylase activity of CYP2B,
      chlorzoxazone 6-hydroxylase activity of CYP2E1 and ethylmorphine N-demethylase
      activity of CYP3A. The results indicate a significant elevation of CYP2E1 and
      CYP3A activities, however, no change in CYP1A and CYP2B activities was seen in
      HDC targeted mice compared to wild type controls with identical genetic
      backgrounds.

PMID- 14642534
TI  - Differential Ca(2+)responses induced by thrombin and thrombin-receptor agonist
      peptides in HSY-EA1 cells.
AB  - We examined the mechanism by which protease-activated receptor (PAR)-1 is
      desensitized by comparing the effect of thrombin and the soluble agonist peptide
      SFLLRN on Ca(2+)responses in HSY-EA1 cells. Thrombin-induced increases in
      cytosolic Ca(2+)concentrations ([Ca(2+)](i)) returned to basal levels within 60
      s, but SFLLRN generated a sustained [Ca(2+)](i)elevation. Interestingly, thrombin
      desensitized cells partially retained their ability to respond to SFLLRN. We
      desensitized PAR-2 by pretreating cells with SLIGKV to confirm that this response
      was not due to PAR-2, which can recognize SFLLRN. The highly specific PAR-1
      agonist peptide TFLLR also increased [Ca(2+)](i)in PAR-2-desensitized cells
      pretreated with thrombin. These observations indicate that thrombin disarms PAR-1
      from further proteolytic activation, but leaves the receptor responsive for non
      tethered ligands.

PMID- 14642536
TI  - Multiple neurotrophic signalling: certain TGF molecules are involved in retinal
      development and maturation, but do they complement one another's actions?

PMID- 14642535
TI  - Hydrogen peroxide-induced apoptosis in pc12 cells and the protective effect of
      puerarin.
AB  - In this study, the effect of puerarin on hydrogen peroxide-induced apoptosis in
      PC12 cells was studied. Exposure of cells to 0.5mM H(2)O(2)may cause significant
      viability loss and apoptotic rate increase. When c-Myc, Bcl-2 and Bax expression
      and caspase-3 activity were measured, using Ac-DEVD-AMC as a substrate, the
      changes in these apoptosis regulatory and effector proteins suggested that the
      elevation of c-Myc, decrease in Bcl-2:Bax protein ratio, and caspase-3 activation
      all play a key role in apoptosis. When cells were treated with puerarin prior to
      0.5 mM H(2)O(2)treatment, a reduction in viability loss and apoptotic rate was
      seen. In addition, c-Myc expression decreased and Bcl-2:Bax ratio increased.
      Puerarin also reduced the H(2)O(2)-induced elevation of caspase-3 activation.
      These results suggest that puerarin can protect neurons against oxidative stress.
      It can block apoptosis in its early stages via the regulation of anti- and pro
      apoptotic proteins, as well as by the attenuation of caspase-3 activation in
      H(2)O(2)-induced PC12 cells.

PMID- 14642537
TI  - Storage and integration in the processing of filler-gap dependencies: an ERP
      study of topicalization and wh-movement in German.
AB  - We recorded event-related brain potentials (ERPs) during the processing of
      unambiguous German sentences containing different types of filler-gap dependency.
      Both topicalization constructions and wh-questions were found to elicit a left
      anterior negativity (LAN) prior to the processing of the subcategorizing verb,
      relative to a gap-free control condition. At the subcategorizing verb, sentences
      containing a wh-dependency produced a parietal positivity (P600) relative to
      topicalization structures. These results support the claim that separable parsing
      processes are involved in the processing of syntactic dependencies, with working
      memory based processes being reflected in an LAN, and the relative difficulty of
      integrating the filler with its subcategorizer reflected in a P600. Integration
      cost but not memory cost was found to be influenced by the type of filler-gap
      dependency involved.

PMID- 14642538
TI  - Slowly progressive pure dysgraphia with late apraxia of speech: a further variant
      of the focal cerebral degeneration.
AB  - We report a longitudinal neuropsychological investigation of a patient with
      slowly progressive pure dysgraphia. Cognitive analysis of writing errors
      suggested a selective impairment of the graphemic buffer. After about seven
      years, the patient developed an apraxia of speech. No other linguistic or
      generalized cognitive impairment occurred subsequently, so that, twelve years
      after the beginning of the disease, the patient showed complete independence in
      daily life and still remained professionally active. Functional neuroimaging
      revealed hypoperfusion confined to left fronto-temporal lobe. This well
      recognizable syndrome does not fit any of the cases described previously in the
      literature. This report therefore, adds another variant to heterogeneous clinical
      spectrum of focal neurodegenerative disorders, further suggesting the opportunity
      of their distinction from pathological processes leading to dementia.

PMID- 14642539
TI  - The unification of mind: Integration of hemispheric semantic processing.
AB  - Seventy-six participants performed a visual half-field lexical decision task at
      two different stimulus onset asynchronies (50 or 750 ms). Word targets were
      primed either by a highly associated word (e.g., CLEAN-DIRTY), a weakly
      associated word (e.g., CLEAN-TIDY), or an unrelated word (e.g., CLEAN-FAMILY)
      projected to either the same or opposite visual field (VF) as the target. In the
      short SOA, RVF-left hemisphere primes resulted in high associate priming
      regardless of target location (ipsilateral or contralateral to the prime) whereas
      LVF-right hemisphere primes produced both high and low associate priming across
      both target location conditions. In the long SOA condition, contralateral priming
      patterns converged, demonstrating only high associate priming in both VF
      locations. The results of this study demonstrate the critical role of
      interhemispheric transfer in semantic processing and indicate a need to elaborate
      current models of semantic processing.

PMID- 14642540
TI  - Age constraints on first versus second language acquisition: evidence for
      linguistic plasticity and epigenesis.
AB  - Does age constrain the outcome of all language acquisition equally regardless of
      whether the language is a first or second one? To test this hypothesis, the
      English grammatical abilities of deaf and hearing adults who either did or did
      not have linguistic experience (spoken or signed) during early childhood were
      investigated with two tasks, timed grammatical judgement and untimed sentence to
      picture matching. Findings showed that adults who acquired a language in early
      life performed at near-native levels on a second language regardless of whether
      they were hearing or deaf or whether the early language was spoken or signed. By
      contrast, deaf adults who experienced little or no accessible language in early
      life performed poorly. These results indicate that the onset of language
      acquisition in early human development dramatically alters the capacity to learn
      language throughout life, independent of the sensory-motor form of the early
      experience.

PMID- 14642541
TI  - Temporal parameters as cues to phrasal boundaries: a comparison of processing by
      left- and right-hemisphere brain-damaged individuals.
AB  - Two experiments were conducted to examine the ability of left- (LHD) and right
      hemisphere-damaged (RHD) patients and normal controls to use temporal cues in
      rendering phrase grouping decisions. The phrase "pink and black and green" was
      manipulated to signal a boundary after "pink" or after "black" by altering pre
      boundary word durations and pause durations at the boundary in a stepwise
      fashion. Stimuli were presented to listeners auditorily along with a card with
      three alternative groupings of colored squares from which to select the presented
      alternative. Results revealed that normal controls were able to use both temporal
      cues to identify the intended grouping. In contrast, LHD patients required longer
      than normal pause durations to consistently identify the intended grouping,
      suggesting a higher than normal threshold for perception of temporal prosodic
      cues. Surprisingly, the RHD patients exhibited great difficulty with the task,
      perhaps due to the limited acoustic cues available in the stimuli.

PMID- 14642542
TI  - Pervasive influence of semantics in letter and category fluency: a
      multidimensional approach.
AB  - We used multidimensional statistical procedures to study semantic and lexical
      processes underlying word retrieval in verbal-fluency performance. Forty healthy
      participants were given a two-choice letter task (i.e., generate items beginning
      with the letter 'A' or 'F', in any order) and a two-choice category task (i.e.,
      generate animal or fruit names, in any order). Using correspondence analysis
      (CoA) and hierarchical clustering (HC), we found evidence of prominent semantic
      organization in both letter and category fluency. For example, a striking
      categorical segregation between animate and inanimate entities emerged during the
      letter task. Analysis of inter-item times revealed strong sequential priming
      effects in both tasks. Taken together, these results indicate that semantic
      facilitation is pervasive in word retrieval processes, even in the letter-fluency
      task, and therefore suggest that the traditional view of letter fluency as a
      purely phonemically based task should be revised. Finally, our findings may help
      explain patterns of verbal-fluency measures obtained in focal brain lesion
      patients.

PMID- 14642543
TI  - Time course of brain activation during graphemic/phonologic processing in
      reading: an ERP study.
AB  - The present study sought to investigate the time course of brain activation
      during grapheme-to-phoneme conversion and phonologic processing of legal Italian
      syllables. To this goal, we monitored a group of right-handed native Italian
      volunteers performing a phonologic decision task (same/different judgments). ERPs
      were recorded from 28 scalp sites during silent reading. Analysis of ERP latency
      showed faster responses to same syllables than to different ones as early as 105
      ms at left temporal electrode site and 160 ms at frontal sites. The first effect
      of phonologic/graphemic incongruity on the amplitude of ERPs was observed at
      lateral occipital/posterior temporal sites (N185), where physiologic responses
      were enhanced to incongruous syllables.

PMID- 14642544
TI  - Word frequency and laterality effects in lexical decision: right hemisphere
      mechanisms.
AB  - Three experiments investigated the role of the right cerebral hemisphere in the
      word frequency effect observed in visual word recognition. The experiments
      examined lexical decisions to low and high frequency words as well as non-words
      in a divided visual field paradigm. Experiment 1 showed a significant word
      frequency effect only for left visual field presentation. Experiment 2 provided a
      partial replication of the results of Experiment 1 with a different set of words.
      In Experiment 3, case alternation was implemented to investigate a possible
      explanation of the findings. Results of the first experiment were replicated in
      the condition without case alternation. In the case-alternated condition, the
      word frequency effect was significant only for right visual field presentations.
      The present findings emphasize the need to consider that information processing
      strategies relevant to hemispheric asymmetries might account in part for the word
      frequency effect.

PMID- 14642545
TI  - Word superiority, pseudoword superiority, and learning to read: a comparison of
      dyslexic and normal readers.
AB  - Identification of letters embedded in briefly presented words (e.g., TABLE),
      pseudowords (e.g., TOBLE), and illegal nonwords (e.g., TPBFE) was measured using
      the Reicher-Wheeler paradigm. Children diagnosed as dyslexic and showing a clear
      disadvantage in recognizing and reading aloud words and pseudowords (compared to
      chronological age-matched controls) showed a pattern of results that was
      qualitatively identical to both reading age and chronological age control
      children. In all three groups a small nonsignificant advantage was obtained for
      letter identification in words compared to pseudowords, and a massive advantage
      for letter identification in pseudowords compared to illegal nonwords. A group of
      adult participants tested with the same materials showed the classic word
      superiority effect as well as a pseudoword advantage over illegal nonwords. These
      results suggest that the pseudoword superiority effect is subtended by
      regularities operating at the level of sublexical orthographic representations
      (orthotactic constraints). This phenomenon could provide a useful tool for future
      investigations of the development of orthotactic constraints during reading
      acquisition.

PMID- 14642546
TI  - The bilingual Loch Ness Monster raises its non-asymmetric head again-or, why
      bother with such cumbersome notions as validity and reliability? Comments on
      Evans et al. (2000).
AB  - All of the experimental studies of the past 25 years combined and the meta
      analyses of their findings have not advanced our knowledge of the lateralization
      of language in bilingual speakers one bit. We are left with a clutter of
      inherently uninterpretable contradictory results. Successive studies do not
      contribute a single brick to the edifice or a single piece to the puzzle-only
      more confusion. study is no exception. So far, there has been no demonstration of
      the validity of any experimental paradigm claiming to measure degree of language
      laterality in bilingual speakers. Experimentation is pointless unless the nature
      of what is alleged to be lateralized is clearly defined and the validity of the
      measures employed has been established. Because of the lack of validity of the
      paradigms used in bilingual laterality studies, experiments and meta-analyses of
      their findings cannot have any scientific significance. Like their predecessors,
      Evans et al. pay lip service to a number of methodological problems, but ignore
      their implications and simply carry on anyway. The authors ought to demonstrate,
      rather than assume, that degree of visual half-field advantage for single words
      corresponds to degree of lateralization of any component of language (even if
      only of words).

PMID- 14642547
TI  - Educational level, socioeconomic status and aphasia research: a comment on Connor
      et al. (2001)--effect of socioeconomic status on aphasia severity and recovery.
AB  - Is there a relation between socioeconomic factors and aphasia severity and
      recovery? describe correlations between the educational level and socioeconomic
      status of aphasic subjects with aphasia severity and subsequent recovery. As
      stated in the introduction by, studies of the influence of educational level and
      literacy (or illiteracy) on aphasia severity have yielded conflicting results,
      while no significant link between socioeconomic status and aphasia severity and
      recovery has been established. In this brief note, we will comment on their
      findings and conclusions, beginning first with a brief review of literacy and
      aphasia research, and complexities encountered in these fields of investigation.
      This serves as a general background to our specific comments on, which will be
      focusing on methodological issues and the importance of taking normative values
      in consideration when subjects with different socio-cultural or socio-economic
      backgrounds are assessed.

PMID- 14642548
TI  - Trends in incidence rates for obesity-associated cancers in the US.
AB  - The purpose of this study was to assess the possible impact of rising prevalence
      of obesity in US adults (since the late 1970s) on incidence rates (1973-1999) for
      cancers strongly associated with obesity, and to estimate the number of incident
      cancers (in 2002) potentially attributable to obesity. Data from a group of high
      quality population-based cancer registries, regarded as generally representative
      of the unknown cancer rates in the entire US, were used to obtain average annual
      age-standardized incidence rates (ASIRs) per 100,000 from 1973 to 1975 through
      1997-1999 for selected obesity-related cancers. Temporal increases in ASIRs were
      evident during the entire period for kidney and adenocarcinomas of the esophagus
      and gastric cardia, while during the 1990's the decline in ASIRs for
      adenocarcinoma of the uterine corpus was reversed and the ASIRs for breast cancer
      continued to increase for age 50+ years, suggesting a potential impact of rising
      obesity prevalence rates. An estimated 41,383 new cancers (about 3.2% of all
      cancers) diagnosed in the US in 2002 may be potentially attributable to obesity.
      Further analytic epidemiologic studies are needed to assess the risks of other
      cancers in relation to both obesity and body fat distribution.

PMID- 14642549
TI  - A dietary enzyme: alpha-methylacyl-CoA racemase/P504S is overexpressed in colon
      carcinoma.
AB  - Epidemiological studies have shown that consumption of red meat increases the
      risk of developing colon cancer. An enzyme, alpha-methylacyl CoA racemase
      (AMACR), also known as P504S, plays an important role in peroxisomal beta
      oxidation of branched-chain fatty acids from red meat and dairy products. High
      expression of AMACR was recently found in prostate cancer. In this study, we
      investigated expression of AMACR in 242 cases of colonic tumors including 176
      colorectal carcinomas, 38 colon adenomas and 28 hyperplastic (non-neoplastic)
      polyps by immunohistochemical analysis. The mRNA levels of AMACR expression in
      normal and colon cancer tissues were assessed by real-time PCR. Significant up
      regulation of AMACR mRNA was found in colon carcinomas compared to normal tissue.
      There was very low or no expression of AMACR protein in normal colon, but AMACR
      was highly expressed in 76 and 75% of well and moderately differentiated colon
      carcinomas, respectively, and in 79% of adenomas. In contrast, only 4% of
      hyperplastic polyps expressed AMACR. Since this enzyme is involved in the
      metabolism of branched-chain fatty acids from beef, milk and dairy products, our
      results provide important molecular information regarding a possible link between
      diet and development of colon cancer. AMACR may also serve as a molecular marker
      for colon cancers and its precursor lesions.

PMID- 14642550
TI  - Predictability of lymph node metastases by preoperative nuclear morphometry in
      squamous cell carcinoma of the tongue.
AB  - AIM: This study was undertaken to assess the predictability of lymph node
      metastases by analyzing preoperative nuclear morphometry of squamous cell
      carcinoma of the tongue. METHODS: Twenty-eight cases of well-differentiated
      squamous cell carcinoma (13 cases with metastasized lymph nodes, 15 node-negative
      cases) were examined. Using a computerized image system, the mean nuclear area,
      the nuclear perimeter, the circular rate, the largest to the smallest dimension
      ratio (LS ratio) of the nuclei, and the coefficient of variation of the nuclear
      area (NACV) were measured. The relationship between these results and the lymph
      node involved was evaluated retrospectively. RESULTS: The nuclear area and
      perimeter were significantly higher in cases with metastasized lymph nodes than
      in node-negative cases (P<0.05). The circular rate was also higher in cases with
      no metastasized lymph nodes than in node-positive cases (P<0.05). The LS ratio
      was higher in cases with metastasized lymph nodes than in node-negative cases
      (P=0.072). The NACV value was also higher in cases with metastasized lymph nodes
      than in node-positive cases, which showed no significant differences (P=0.322).
      CONCLUSIONS: Preoperative quantitative estimations of nuclear features could
      provide a feasible criterion for the prediction of lymph node metastases in
      squamous cell carcinoma of the tongue.

PMID- 14642551
TI  - Molecular and histopathologic predictors of distant failure in endometrial
      cancer.
AB  - A case-cohort study was designed to correlate various histopathologic and
      molecular variables with distant failure in endometrial cancer by analyzing
      phenotypic and molecular indices in hysterectomy specimens. From an overall
      population of 283 patients with endometrial cancer, we selected a cohort
      including all 49 patients who experienced any recurrence and 76 randomly chosen
      patients without recurrence. Expression of nuclear proliferating cell nuclear
      antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined
      with digital image analysis, and cell membrane HER-2/neu and bcl-2 were
      quantitated visually. Ploidy and DNA indices were determined with flow cytometry.
      Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated
      because of technical inadequacies. Distant failures were defined as primary
      recurrences that developed outside the pelvis or vagina. Median follow-up was 91
      months. Distant failures occurred in 13% of the patients. Cervical stromal
      invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes,
      positive peritoneal cytology, lymphovascular invasion, grade 3 histology,
      nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining,
      aneuploidy, S-phase fraction > or =9%, proliferative index > or =14%, and DNA
      index > or =1.5 significantly (P<0.05) predicted distant failures. However, a
      logistic regression model identified only p53 (OR=43.73; P<0.005), lymphovascular
      invasion (OR=11.59; P<0.001), and cervical stromal invasion (OR=11.29; P=0.001)
      as cogent predictors of distant failures. Only 3% of patients without any of
      these three predictors developed distant failures compared with 36% of those with
      at least one of the three (P<0.01). Thus, locoregional therapy may be
      insufficient when at least one of these predictors is present.

PMID- 14642552
TI  - A randomized trial of telephone counseling to promote screening mammography in
      two HMOs.
AB  - Tailored telephone counseling (TTC) is effective in increasing utilization of
      screening mammography, but has received limited testing on a large scale in a
      contemporary HMO setting in which most eligible women get regular screening. We
      conducted a randomized controlled trial comparing TTC to an active control
      (mailed reminders) among women aged 50-80 enrolled in two HMOs in New England
      (n=12,905). Over a 1-year period counselors attempted to contact women in the
      intervention arm who had not had a mammogram within the last 15 months. The
      absolute increase in mammography use due to the intervention was 4.9% (OR 1.3,
      95% CI 1.0-1.6) in one HMO and 3.1% (OR 1.2, 95% CI 1.0-1.3) in the other. We
      estimated that one additional woman was screened for each 10.9 women eligible for
      counseling. An intervention process analysis documented a high level of
      acceptance of TTC and identified subgroups that could be targeted for counseling
      to improve the efficiency of TTC.

PMID- 14642553
TI  - Effectiveness of a dynamic breast examination training model to improve clinical
      breast examination (CBE) skills.
AB  - Despite the potential utility of clinical breast examination (CBE), doctors'
      palpation skills are often inadequate and difficult to train. CBE sensitivity
      ranges from 39-59%, in part because current training does not effectively teach
      tactile skills. To address CBE training limitations, we developed a breast
      examination training model with 15 dynamically controlled lumps, set to desired
      hardness within underlying rib and muscle structures, in a silicone breast. In an
      experiment of 48 medical students, training with the dynamic model increased lump
      detection by 1.35 lumps compared to 0.60 lumps for a traditional breast model
      (P=0.008), reduced false positives by -0.70 lumps compared to +0.42 lumps
      (P=0.0277), and demonstrated skill transfer with a 1.17 lump detection
      improvement on the traditional device compared to only a 0.17 lump detection
      improvement by traditional device trainees on the dynamic device (P<0.001).
      Findings demonstrate the advantage of the dynamic model over conventional models
      in training CBE tactile skills.

PMID- 14642554
TI  - Determinants of participation of women in a cervical cancer visual screening
      trial in rural south India.
AB  - The efficacy of a single round of screening of visual inspection with acetic acid
      (VIA) on cervical cancer incidence and mortality is investigated in a cluster
      randomized controlled trial in south India. Women aged 30-59 years in 113
      clusters in Dindigul District were randomized to VIA screening by nurses (57
      clusters, 48,225 eligible women) and to a control group (56 clusters, 30,167
      women). 30,577 (63.4%) eligible women participated in screening. Younger,
      educated, married, multiparous, low-income women and those who have had tubal
      sterilization had a higher compliance with screening. Of the 2069 women diagnosed
      with CIN and invasive cancer, 1498 (72.4%) received treatment. Young women, those
      who practiced contraception and women with high-grade precursor lesions and
      invasive cancers were more likely to comply with treatment. In summary, our study
      indicates that women accept screening with VIA by nurses and a moderate level of
      compliance with screening and treatment can be reached through appropriate
      service delivery systems including health education activities, personal
      invitations, clinics in proximity to the target women, and testing and treatment
      in the same session. Our results imply that integration of screening activities
      with primary health services seems to have the potential to replicate most of
      these service delivery conditions in routine programs.

PMID- 14642555
TI  - Follow-up care of women with an abnormal cytology in a low-resource setting.
AB  - STUDY PURPOSE: We ascertained the follow-up care after an abnormal cytology
      (Papanicolaou) screening in the San Marti;n region of Peru and assessed the
      status of women who had not received adequate care. BASIC PROCEDURES: We
      identified women with an abnormal cytology and assessed their medical records,
      laboratory registries, death certificates and interviewed them at home. Re
      screening, diagnosis and treatment were offered. MAIN FINDINGS: Only 46 (25%) of
      the 183 women identified received appropriate follow-up care. At re-screening 31
      (34%) had a normal result, 9 (10%) were diagnosed with CIN1 and 50 (56%) had CIN2
      or worse. PRINCIPAL CONCLUSIONS: In this setting, follow-up care after an
      abnormal cytology was very poor and could explain the lack of impact of cervical
      cancer screening. Women with an abnormal cytology constitute a high-risk group
      that should be a priority for health services.

PMID- 14642556
TI  - Prevalence and persistence of human papillomavirus in postmenopausal age women.
AB  - Little is known about the prevalence and persistence of human papillomavirus
      (HPV) in older women, or about the association between hormone replacement
      therapy (HRT) use and HPV detection. Like oral contraceptives, HRT hormones may
      upregulate viral expression and subsequent risk of genital cancer. Postmenopausal
      women seeking routine gynecologic care were evaluated for HPV infection, testing
      cervical/vaginal cytology by PCR/DNA sequencing. The prevalence of HPV was 14%;
      6% had oncogenic types and 5.8% had persistent infection. Although risk of HPV
      detection was non-significantly elevated after adjustment for age and HPV-related
      risk factors among current (adjusted odds ratio (OR)=2.3) and past (adjusted
      OR=3.2) hormone users compared to never users, past users had a significantly
      higher risk using combination HRT regimens with increasing duration (adjusted
      OR=1.8 per year; 95% confidence interval (CI)=1.1-3.1). These findings suggest
      that a significant percentage of older women are infected with HPV. This may put
      them at increased risk of genital cancers with longer use of HRTs. Additional
      studies are needed.

PMID- 14642557
TI  - Induction of cell cycle arrest and apoptosis in human cervix carcinoma cells
      during therapy by cisplatin.
AB  - The aim of the therapy of human malignancies is the inhibition of cell
      proliferation and/or induction of apoptosis. We studied the kinetics of the
      morphological and biochemical changes in HeLa cells during chemotherapy by
      cisplatin (CP). Apoptosis was evaluated by scoring of cells exhibiting changes
      characteristic for early and late stages of apoptosis as determined by Hoechst
      33258 staining and by examination of positive reaction for activated caspase-3.
      Expression and intracellular localization of distinct proteins was analyzed by
      immunoblotting of subcellular fractions and segregation of nucleoli by
      immunocytochemistry. Chromatin fragmentation characteristic for apoptosis was
      observed in single cells after 3h cisplatin. A strong cytoplasmic accumulation of
      cytochrome C detected by immunoblotting 6h post-treatment was accompanied by an
      activation of caspase-9. Neither inhibition of cell division nor blocking of DNA
      replication preceded the onset of apoptosis. Our results show that after short
      treatment by CP, cell proliferation and apoptosis concomitantly occurred.

PMID- 14642558
TI  - Helicobacter pylori seroprevalence in patients with cirrhosis of the liver and
      hepatocellular carcinoma.
AB  - BACKGROUND: Infection by Helicobacter hepaticus causes chronic hepatitis and
      hepatocellular carcinoma (HCC) in mice, and Helicobacter pylori (H. pylori)
      genomic sequences have been demonstrated in the liver of patients with HCC. H.
      pylori infection reportedly occurs with high frequency in patients with cirrhosis
      but none of the studies has investigated it in subjects with cirrhosis and
      superimposed HCC. In this case-control study, we searched for the seroprevalence
      of H. pylori infection in patients with HCC. PATIENTS AND METHOD: Forty-six
      patients (30 males, 16 females, mean age 69 years) with HCC and hepatitis C virus
      (HCV)-related cirrhosis were compared to 46 sex and age (+/-1 year) matched
      patients presenting consecutively to the Emergency Department of Molinette
      Hospital of Torino. All subjects were tested for presence in serum of IgG
      antibodies against H. pylori and the result was analyzed using the chi-square
      test. RESULTS: H. pylori seropositivity was more prevalent among patients with
      HCC (36/46, 78.2%) than in controls (25/46, 54%) (P<0.05) (OR 3.02, 95%
      confidence interval ). Twenty-five out of 30 (83.3%) male patients showed
      seropositivity at a variance with 16/30 (53%) in the controls (P<0.05); 11 out of
      16 (68.7%) female patients were seropositive versus 9 out of 16 (56.2%) control
      subjects (P=n.s.). CONCLUSION: Seroprevalence of antibodies to H. pylori was
      found to be higher in patients with HCC than in controls.

PMID- 14642559
TI  - Characteristics and prognosis of hepatocellular carcinoma detected in sustained
      responders to interferon therapy for chronic hepatitis C.
AB  - Interferon (IFN) therapy allows the eradication of hepatitis C virus (HCV) in
      some part of patients with chronic hepatitis C which is major cause of
      hepatocellular carcinoma (HCC). To clarify characteristics and prognoses of HCC
      detected in these patients (sustained responders to IFN), we compared HCC in
      sustained responders with HCC detected in patients without a sustained response
      (non-sustained responders). Characteristics and prognoses were compared in nine
      cases of HCC detected in sustained responders after IFN therapy and 61 cases of
      HCC detected in non-sustained responders at one of five our institutions. HCC in
      sustained responders often were larger (P=0.0051), less differentiated tumor
      (P=0.0084) than HCC in non-sustained responders when it was detected. No
      differences were observed in overall survival rate between sustained responders
      and non-sustained responders, but disease-free survival was higher in cases of
      HCC in sustained responders (P=0.0494). HCC detected in sustained responders
      often appear more advanced when detected than HCC in non-sustained responders,
      but recurrence seems to be less frequent when the initial HCC is treated
      sufficiently.

PMID- 14642560
TI  - Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in
      terminally differentiated myocytes and proliferating fibroblasts from the rat
      heart.
AB  - Nucleotide excision repair (NER) is the principal pathway for the removal of a
      wide range of DNA helix-distorting lesions. Two NER subpathways have been
      identified, i.e. global genome repair (GGR) and transcription-coupled repair
      (TCR). Little is known about the expression of NER pathways in differentiated
      cells. We assessed the repair of UV-induced cyclobutane pyrimidine dimers (CPD)
      and 6-4-photoproducts (6-4 PP) in terminally differentiated myocytes and
      proliferating fibroblasts isolated from the hearts of neonatal rats. Myocytes and
      fibroblasts were found to carry out efficient removal of 6-4 PP but display poor
      repair of CPD by GGR. Furthermore, both cell types were found to carry out TCR of
      CPD, thus mimicking the repair phenotype of established rodent cell lines. The
      inefficient repair of CPD at the genome overall level occurs in the absence of
      massive apoptosis, but goes along with an undetectable level of transcription of
      the p48 gene, known to be mutated in xeroderma pigmentosum group E (XP-E)
      patients and recently proposed to be essential for repair of CPD in nonexpressed
      DNA. Taken together, the results suggest that primary non-dividing cardiac
      myocytes and proliferating fibroblasts from rat heart selectively remove CPD from
      the transcribed strand of transcriptionally active genes. GGR of CPD is poor due
      to the absence of p48 expression.

PMID- 14642561
TI  - Deficiency of Caenorhabditis elegans RecQ5 homologue reduces life span and
      increases sensitivity to ionizing radiation.
AB  - Gene expression and RNA interference phenotypes were investigated for a
      Caenorhabditis elegans homologue (Ce-RCQ-5) of human RecQ5 protein. Expression of
      the mRNA was observed by in situ hybridization from earliest embryogenesis and
      gradually decreased during late embryogenesis. Ce-RCQ-5 was immuno-localized in
      the nuclei of embryos, germ cells, and oocytes and also in the nuclei of various
      somatic cells of larvae and adults. Despite ubiquitous expression in
      postembryonic cells, RCQ-5 protein expression was highest in intestinal cells,
      which was confirmed by tagging the gene expression with green fluorescence
      protein. When endogenous Ce-rcq-5 gene expression was inhibited by RNA
      interference, no clear phenotypes were observed during development. However, C.
      elegans life span was reduced by 37% due to RNA interference of rcq-5 gene,
      suggesting its possible role in maintenance of genomic stability, as has been
      ascribed to other RecQ family DNA helicases. In addition, C. elegans became
      significantly more sensitive to ionizing radiation after inhibition of rcq-5 gene
      expression, indicating an involvement of C. elegans RCQ-5 in a cellular response
      to DNA damage, possibly in DNA repair.

PMID- 14642562
TI  - MEC1-dependent phosphorylation of yeast RPA1 in vitro.
AB  - Replication protein A (RPA) is a conserved single-stranded DNA (ssDNA) binding
      protein with well-characterized roles in DNA metabolism. RPA is phosphorylated in
      response to genotoxic stress and is required for efficient checkpoint function,
      although these aspects of RPA function are not well understood. We have
      investigated the association between RPA and the checkpoint kinase Mec1 in yeast.
      RPA and Mec1 were found to be physically associated during unperturbed cell
      growth and in response to DNA damage. Using a Mec1 immunoprecipitate (IP)-kinase
      assay, we show that the two large subunits, RPA1 and RPA2, are good substrates
      for Mec1 kinase. The major phosphorylation site of RPA1 was further investigated
      as it was found to be localized to its amino terminus (RPA1N), which is a non
      ssDNA binding domain implicated in regulatory function. This phosphorylation site
      mapped to serine 178 and phosphorylation-defective mutant protein, expressed from
      rfa1-S178A, showed reduced physical interaction with Mec1. Phenotypic analysis in
      vivo revealed that the rfa1-S178A mutation affected the kinetics of RPA1 and
      Rad53 phosphorylation but did not otherwise affect the checkpoint response. We
      suggest that phosphorylation of RPA1N by Mec1 may function together with other
      checkpoint events to regulate the checkpoint response.

PMID- 14642563
TI  - Immunofluorescent localization of the murine 8-oxoguanine DNA glycosylase (mOGG1)
      in cells growing under normal and nutrient deprivation conditions.
AB  - OGG1 is a major DNA glycosylase in mammalian cells, participating in the repair
      of 7,8-dihydro-8-oxoguanine (8-oxoguanine, 8-oxoG), the most abundant known DNA
      lesion induced by endogenous reactive oxygen species in aerobic organisms. 8-oxoG
      is therefore often used as a marker for oxidative DNA damage. In this study,
      polyclonal and monoclonal antibodies were raised against the purified wild-type
      recombinant murine 8-oxoG DNA glycosylase (mOGG1) protein and their specificity
      against the native enzyme and the SDS-denatured mOGG1 polypeptide were
      characterized. Specific antibodies directed against the purified wild-type
      recombinant mOGG1 were used to localize in situ this DNA repair enzyme in
      established cell lines (HeLa cells, NIH3T3 fibroblasts) as well as in primary
      culture mouse embryo fibroblasts growing under either normal or oxidative stress
      conditions. Results from these studies showed that mOGG1 is localized to the
      nucleus and the cytoplasm of mammalian cells in culture. However, mOGG1 levels
      increase and primarily redistribute to the nucleus and its peripheral cytoplasm
      in cells exposed to oxidative stress conditions. Immunofluorescent localization
      results reported in this study suggest that susceptibility to oxidative DNA
      damage varies among mammalian tissue culture cells and that mOGG1 appears to
      redistribute once mOGG1 cell copy number increases in response to oxidative DNA
      damage.

PMID- 14642564
TI  - Bufalin influences the repair of X-ray-induced DNA breaks in Chinese hamster
      cells.
AB  - The bufadienolide bufalin, a component of the Chinese medicine chan'su, has been
      reported to selectively inhibit the growth of various lines of human cancer
      cells, due at least in part to its specific effect on topoisomerase (topo) II. We
      have treated Chinese hamster ovary (CHO) cells with doses of bufalin that result
      in a dramatic reduction in both the level and catalytic activity of topo II
      without any concomitant induction of DNA damage, as assessed by the comet assay.
      When cells were pre-treated with bufalin and then irradiated with X-rays, a
      follow-up study revealed that the kinetics of DNA repair was clearly affected,
      with a general delay in the restoration of DNA to the situation observed in non
      irradiated controls. The possible involvement of topo II in radiation damage
      repair is discussed.

PMID- 14642565
TI  - Altered translesion synthesis in E. coli Pol V mutants selected for increased
      recombination inhibition.
AB  - Replication of damaged DNA, also termed as translesion synthesis (TLS), involves
      specialized DNA polymerases that bypass DNA lesions. In Escherichia coli,
      although TLS can involve one or a combination of DNA polymerases depending on the
      nature of the lesion, it generally requires the Pol V DNA polymerase (formed by
      two SOS proteins, UmuD' and UmuC) and the RecA protein. In addition to being an
      essential component of translesion DNA synthesis, Pol V is also an antagonist of
      RecA-mediated recombination. We have recently isolated umuD' and umuC mutants on
      the basis of their increased capacity to inhibit homologous recombination.
      Despite the capacity of these mutants to form a Pol V complex and to interact
      with the RecA polymer, most of them exhibit a defect in TLS. Here, we further
      characterize the TLS activity of these Pol V mutants in vivo by measuring the
      extent of error-free and mutagenic bypass at a single (6-4)TT lesion located in
      double stranded plasmid DNA. TLS is markedly decreased in most Pol V mutants that
      we analyzed (8/9) with the exception of one UmuC mutant (F287L) that exhibits
      wild-type bypass activity. Somewhat unexpectedly, Pol V mutants that are
      partially deficient in TLS are more severely affected in mutagenic bypass
      compared to error-free synthesis. The defect in bypass activity of the Pol V
      mutant polymerases is discussed in light of the location of the respective
      mutations in the 3D structure of UmuD' and the DinB/UmuC homologous protein Dpo4
      of Sulfolobus solfataricus.

PMID- 14642566
TI  - The transcription factor, NFI/CTF plays a positive regulatory role in expression
      of the hSMUG1 gene.
AB  - SMUG1 is a recently discovered uracil-DNA glycosylase with the ability to remove
      uracil from single-stranded as well as double-stranded DNA. SMUG1 also has the
      capacity to excise oxidized pyrimidine bases such as 5-hydroxymethyluracil and 5
      formyluracil from DNA. Very little is known about the regulation of this enzyme.
      Therefore, we undertook this study to begin to elucidate the mechanisms of hSMUG1
      gene expression. Northern blot analysis performed on mRNAs derived from different
      cell lines reveals that the steady-state levels of hSMUG1 transcript are about 10
      fold lower relative to UDG. In addition to the 1.6kb transcript known to encode a
      functional hSMUG1 protein, an alternate 0.7kb transcript was uncovered that
      contains an open reading frame. Interestingly, this alternate transcript is
      missing a carboxy-terminal domain which is necessary for catalytic activity.
      Utilizing a luciferase reporter assay system we show that significant promoter
      activity is associated with a 2000bp region, located immediately upstream of the
      first transcribed, non-translated exon. 5' deletion analysis of this 2000bp
      region reveals that there are both negative and positive regulatory elements that
      control expression of SMUG1. Using electrophoretic mobility shift analysis we
      show that a number of DNA-protein complexes are formed within the region (-705 to
      -604) of positive regulation. At least two of these complexes contain the
      transcription factor NFI/CTF as demonstrated by oligonucleotide competition
      studies with NFI/CTF consensus sequence containing both protein-binding half
      sites. We further demonstrate that purified NFI-C protein will bind to this
      positive regulatory region within the hSMUG1 gene. DNase I footprint analysis
      reveals that the 3' half-site is protected when using crude nuclear extract as a
      protein source. However, the introduction of mutations into either or both of the
      half-sites indicates that the individual half-sites contribute to NFI/CTF
      binding. Overexpression of NFI-C in NIH-3T3 cells results in an increase in SMUG1
      enzyme activity. Collectively, these data indicate that the NFI/CTF consensus
      site may function as a cis-element in the SMUG1 promoter and that this
      transcription factor contributes to the positive regulation of SMUG1 gene
      expression.

PMID- 14642567
TI  - Chromosome instability and tumor predisposition inversely correlate with BLM
      protein levels.
AB  - Independent mouse models for Bloom syndrome (BS) exist, each thought to disrupt
      Blm gene function. However, animals bearing these alleles exhibit distinct
      phenotypes. Blm(tm1Ches) and Blm(tm1Grdn) homozygous mutant animals exhibit
      embryonic lethality while in another, Blm(tm3Brd), homozygosity yields viable,
      fertile animals with a cancer predisposition. Further characterization reveals
      the Blm(tm3Brd) allele to be a hypomorph, producing a diminished quantity of
      normal mRNA and protein. The Blm(tm3Brd) allele produces sufficient normal
      protein to rescue Blm(tm1Ches) lethality. Evaluation of viable animals reveals an
      inverse correlation between the quantity of Blm protein and the level of
      chromosome instability and a similar genotypic relationship for tumor
      predisposition indicating that Blm protein is rate limiting for maintaining
      genomic stability and the avoidance of tumors.

PMID- 14642568
TI  - Rescue of Xrcc1 knockout mouse embryo lethality by transgene-complementation.
AB  - Xrcc1 knockout embryos show increased DNA breakage and apoptosis in tissues of
      the embryo proper prior to death at embryonic day E6.5. An additional deficiency
      in Trp53 allows Xrcc1(-/-) embryos to enlarge slightly and initiate gastrulation
      although ultimately death is delayed by less than 24h. Death presumably results
      from DNA damage that reaches toxic levels in the post-implantation mouse embryo.
      To investigate the level of XRCC1 protein needed for successful mouse
      development, we derived Xrcc1 transgene-complemented Xrcc1(-/-) mice that express
      Xrcc1 within the normal range or at a greatly reduced level (<10% normal). The
      greatly reduced XRCC1 protein level destabilized the XRCC1 partner protein DNA
      ligase III (LIG3) but still allowed for successful mouse development and healthy,
      fertile adults. Fibroblasts from these animals exhibited almost normal alkylation
      sensitivity measured by differential cytotoxicity. Thus, a large reduction of
      both XRCC1 and DNA ligase III has no observable effect on mouse embryogenesis and
      post-natal development, and no significant effect on cellular sensitivity to DNA
      alkylation. The presence of XRCC1, even at reduced levels of expression, is
      therefore capable of supporting mouse development and DNA repair.

PMID- 14642569
TI  - Expression of Deinococcus radiodurans PprI enhances the radioresistance of
      Escherichia coli.
AB  - PprI, a newly identified gene switch responsible for extreme radioresistance of
      Deinococcus radiodurans, plays a central regulatory role in multiple DNA damage
      repair and protection pathways in response to radiation stress [Biochem. Biophy.
      Res. Commun. 306 (2003) 354]. To evaluate whether PprI also functions in the
      radioresistance in other organisms, D. radiodurans PprI protein (Deira-PprI) was
      expressed in Escherichia coli. The complemented E. coli strain showed an increase
      of approximately 1.6-fold radioresistance with a high dose of gamma irradiation.
      Immunoblotting assays showed that the expression of Deira-PprI in E. coli
      resulted in a significant increase in RecA protein expression following high dose
      ionizing radiation. The expression of Deira-PprI protein also significantly
      enhanced the scavenging ability of free radicals by inducing the enzymatic
      activity of KatG. These results indicate that exogenous expression of Deira-PprI
      promotes DNA repair and protection pathways and enhances the radioresistance of
      E. coli.

PMID- 14642570
TI  - Developmental retinal apoptosis in Ku86-/- mice.
AB  - The nonhomologous DNA end-joining pathway (NHEJ), a major pathway for repairing
      DNA double-strand breaks (DSBs), is essential for maintaining genomic stability.
      Knockout animals for components in this pathway demonstrate a distinct pattern of
      cell death in the developing brain. Here we demonstrate that cell death is also
      present in the developing retina of E14.5 Ku86-deficient mouse embryos,
      suggesting that the increase in cell death in the retina is associated with
      chromosome breaks. In the adult retina, we do not find continuing apoptosis, but
      interestingly, we find decreased numbers of total neuronal cells. This suggests
      that the increased retinal apoptosis during embryogenesis causes the reduction in
      cell numbers observed in the adult retina. This analysis of the retina provides
      the first opportunity to formally test the hypothesis that embryonic apoptosis
      accounts for reduced total cell numbers in adult Ku86-/- mice.

PMID- 14642571
TI  - Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4
      endonuclease complex formation and nuclear localization.
AB  - The Saccharomyces cerevisiae Mms4 and Mus81 proteins form a specific complex,
      which functions as an endonuclease specific for branched DNA molecules and
      protects cells from killing by DNA alkylation damage, but not damage induced by
      ionizing radiations. In an effort to further understand the structure and
      functions of the Mus81-Mms4 complex, we attempted to define domains required for
      complex formation and nuclear localization through deletion and mutagenesis
      analyses. Combined yeast two-hybrid and co-immunoprecipitation experiments
      indicate that the C-terminal 100 amino acids of both Mus81 and Mms4 are required
      and sufficient for heterodimer formation. However, a single amino acid
      substitution in Mms4 in the N-terminal region is able to abolish the interaction,
      which suggests that the three-dimensional structure is also important for Mms4 to
      interact with Mus81. By fusion to green fluorescent protein and in vivo
      subcellular localization studies, we demonstrate that Mms4 and Mus81 are nuclear
      proteins and can be localized to the nucleus independently. Deletion analyses
      indicate that one of two putative nuclear localization signals (residues 244-263)
      in Mms4 is required for localization, whereas the N-terminal half of Mus81 is
      necessary and sufficient for its localization to the nucleus.

PMID- 14642572
TI  - Arsenite and its biomethylated metabolites interfere with the formation and
      repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and
      Fpg.
AB  - The underlying mechanisms of arsenic carcinogenicity are only poorly understood
      and especially the role of biomethylation is still a matter of debate. Besides
      the induction of oxidative DNA damage the interference with DNA repair processes
      have been proposed to contribute to arsenic-induced carcinogenicity. Within the
      present study the effects of arsenite and its mono- and dimethylated trivalent
      and pentavalent metabolites on BPDE-induced DNA adduct formation and repair has
      been investigated and compared in cultured human lung cells. Whereas only
      arsenite and MMA(III) increased BPDE-DNA adduct formation, arsenite (>/=5
      microM), the trivalent (>/=2.5 microM) and the pentavalent (>/=250 microM)
      metabolites diminished their repair at non-cytotoxic concentrations. As potential
      molecular targets, interactions with the zinc finger domain of the human XPA
      protein (XPAzf) and the Escherichia coli zinc finger protein Fpg, involved in NER
      and BER, respectively, have been investigated. All trivalent arsenicals were able
      to release zinc from XPAzf; furthermore, MMA(III) and DMA(III) inhibited the
      activity of isolated Fpg. Altogether the results suggest that besides arsenite,
      especially the trivalent methylated metabolites may contribute to diminished NER
      at low concentrations.

PMID- 14642574
TI  - Photo-induced DNA cleavage reaction characteristics of propargylic sulfones
      possessing anthraquinone chromophore.
AB  - DNA cleavage potency of propargylic sulfones possessing anthraquinone chromophore
      1 under UV-irradiation was evaluated in comparison with the dark reaction. 1
      showed inefficient DNA cleavage activity, while having considerably strong DNA
      binding ability. This result is accounted for by spatial conditions that the
      activated alkylating allenic site of intercalated 1 could not effectively
      approach to DNA bases, most probably guanine moiety, and thereby led to
      insufficient DNA strand cleavage. In contrast, the DNA cleavage activity of 1 was
      notably enhanced upon UV-irradiation (lambda(ex)=365 nm) followed by incubation.
      Under UV-irradiation, further DNA cleavage were occurred primary at 5'-G of GG
      steps within DNA. A DNA cleavage mechanism for 1, by which photo-induced one
      electron oxidation of 5'-G of GG steps may occur along with ordinary alkylation,
      has been proposed.

PMID- 14642575
TI  - Structural requirements of flavonoids for inhibition of protein glycation and
      radical scavenging activities.
AB  - To clarify the structural requirements of flavonoids for formation of advanced
      glycation end-products (AGEs), various flavonoids were examined. The results
      suggested the following structural requirements of flavonoids for the inhibition
      of AGEs formation: (1). as the hydroxyl groups at the 3'-, 4'-, 5-, and 7
      positions increased in number, the inhibitory activities became stronger; (2).
      the activities of flavones were stronger than those of corresponding flavonols,
      flavanones, and isoflavones; (3). methylation or glucosylation of the 4'-hydroxyl
      group of flavones, flavonols, and flavanones reduced activity; (4). methylation
      or glycosylation of the 3-hydroxyl group of flavonols tended to increase
      activity; (5). glycosylation of the 7-hydroxyl group of flavones and isoflavones
      reduced activity. In addition, various flavonoids with strong AGEs formation
      inhibitory activity tended to exhibit strong scavenging activity for 1,1-diphenyl
      2-picrylhydrazyl and superoxide anion radicals, with several exceptions.

PMID- 14642576
TI  - 3-D-QSAR study and molecular docking of methionyl-tRNA synthetase inhibitors.
AB  - The three-dimensional quantitative structure-activity relationships of 57 2
      [(aminopropyl)amino]-4(1H)-quinolinone analogues as Staphylococcus aureus
      methionyl-tRNA synthetase (MetRS) inhibitors with excellent antibacterial profile
      were investigated and docking studies were performed. The CoMFA analysis provided
      a model with a q(2) value of 0.579 and an r(2) value of 0.970, in which the good
      correlation between the MetRS inhibitory activities (IC(50)) and the steric and
      electrostatic molecular fields around the analogues was examined. Two inhibitors
      (1 and 17) were docked into the binding pocket of Escherichia coli MetRS imported
      from the X-ray crystal structure of the MetRS-methionine complex, and the details
      of their interaction with the amino acids of the active site are discussed.

PMID- 14642577
TI  - Synthesis of a [2-pyridinyl-18F]-labelled fluoro derivative of (-)-cytisine as a
      candidate radioligand for brain nicotinic alpha4beta2 receptor imaging with PET.
AB  - In recent years, there has been considerable effort to design and synthesize
      radiotracers suitable for use in Positron Emission Tomography (PET) imaging of
      the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new
      fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2
      fluoropyridinyl)cytisine (3, K(i) values of 24 and 3462 nM for the alpha4beta2
      and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical
      steps from (-)-cytisine and labelled with fluorine-18 (T(1/2): 119.8 min) using
      an efficient two-step radiochemical process [(a). nucleophilic heteroaromatic
      ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative,
      (b). TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67
      GBq) of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3, 2-3 Ci/micromol or 74
      111 GBq/micromol) were easily obtained in 70-75 min starting from a 100 mCi (3.7
      GBq) aliquot of a cyclotron-produced [18F]fluoride production batch (20-45% non
      decay-corrected yield based on the starting [18F]fluoride). The in vivo
      pharmacological profile of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) was
      evaluated in rats with biodistribution studies and brain radioactivity monitoring
      using intracerebral radiosensitive beta-microprobes. The observed in vivo
      distribution of the radiotracer in brain was rather uniform, and did not match
      with the known regional densities of nAChRs. It was also significantly different
      from that of the parent compound (-)-[3H]cytisine. Moreover, competition studies
      with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not
      reduce brain uptake of the radiotracer. These experiments clearly indicate that (
      )-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) does not have the required
      properties for imaging nAChRs using PET.

PMID- 14642578
TI  - Synthesis of new glycyrrhetinic acid (GA) derivatives and their effects on
      tyrosinase activity.
AB  - To synthesize glycyrrhetinic acid (GA) derivatives (3, 4, 5, 10, 13, 14, 15, and
      16), we first removed the ketonic group in the C-11 position, and the carboxylic
      function at the C-30 position was kept intact, reduced to an alcohol, or
      transformed to an aldehyde corresponding derivatives 10 and 13. Glycyrrhetinic
      acid (GA) derivatives (3, 4, 5, 15, and 16) were coupled with 4-amino
      piperpyridine derivatives (12 and 14) and 4-fluorobenzyl bromide at C-30
      carboxylic acid position of glycyrrhetinic acid. In subsequent tyrosinase assays,
      we found that GA derivatives 4, 5, and 16 were not active at early time points,
      but strongly inhibited tyrosinase activity at late time points. Of the GA
      derivatives examined, derivative 5 was most active, with an IC(50) value of 50
      microM after 2 h reaction. IC(50) values of derivatives 4 and 16 were 120 and 170
      microM, respectively. Further kinetic data indicated that these derivatives are
      slow-binding inhibitors of tyrosinase. The time-dependent inhibition was reversed
      when vitamin C or kojic acid was used, that is, both compounds showed active
      inhibition at early time points. These results suggest that GA derivatives are
      much more stable than vitamin C or kojic acid, although their intrinsic
      inhibitory potentials are relatively low. Higher stability and activity suggest
      that GA derivative 5 might be a useful candidate for skin whitening.

PMID- 14642579
TI  - Quantitative structure-activity relationship study on sulfanilamide schiff's
      bases: carbonic anhydrase (CA) inhibitors.
AB  - The paper deals with quantitative structure-activity studies on a group of
      sulfanilamide Schiff's base inhibitors of carbonic anhydrase (CA) using distance
      based topological indices. The regression analysis of the data has shown that the
      activities of the compounds used in inhibiting Carbonic AnhydraseII (CAII)
      activity can be modeled excellently in multi-parametric model in that some
      indicator parameters are also involved. The results are discussed critically.

PMID- 14642580
TI  - Synthesis of glycosylated beta-amino hydroxamates as new class of antimalarials.
AB  - Glycosylated beta-amino acids (3-18, 38, 39), obtained by hydrolysis of
      glycosylated beta-amino esters on reaction with hydroxylamine hydrochloride in
      presence of DIC/DCC afforded glycosyl beta-amino hydroxamates (19-34, 40, 41) in
      fair to good yields. Compounds (19-34, 40, 41) were screened against human
      malarial parasite Plasmodium falciparum in vitro for their schizontocidal
      activity. Compounds (19, 24, 26, 28, 40 and 41) exhibited good activity at 2
      microg/mL concentrations.

PMID- 14642581
TI  - Ultrasensitive assay of azithromycin in medicine and bio-fluids based on its
      enhanced luminol-H(2)O(2) chemiluminescence reaction using flow injection
      technique.
AB  - A simple flow injection chemiluminescence method with synergistic enhancement has
      been investigated for the rapid and sensitive determination of azithromycin. The
      synergistic action was significant in the chemiluminescence system of luminol
      hydrogen peroxide with azithromycin as an enhancer. The enhanced
      chemiluminescence intensity was linear with the concentration of azithromycin
      over the range from 0.1 pg x mL(-1) to 1.0 ng x mL(-1) (r(2=)0.9988) with a
      detection limit (3sigma) of 0.04 pg x mL(-1). At a flow rate of 2.0 mL x min(-1),
      a complete analytical process could be performed within 0.5 min, including
      sampling and washing, with a relative standard deviation of less than 3.0%. The
      proposed method was applied successfully in the assay of azithromycin in
      pharmaceutical preparations, human urine and serum without any pre-treatment
      procedure.

PMID- 14642582
TI  - Synthetic ceramide analogues as skin permeation enhancers: structure-activity
      relationships.
AB  - The study presents new information about the structure-activity relationships of
      the skin permeation enhancers. A series of ceramide analogues including eight
      different polar head groups and six different chain lengths was synthesised. The
      compounds were evaluated as permeation enhancers in vitro using porcine skin. The
      physico-chemical parameters of the tested compounds obtained by computer
      modelling were used to evaluate, by multiple linear regression, the enhancement
      ratios (ERs) of the compounds. The regression analysis suggests that the hydrogen
      bonding ability of the compounds is inversely related to the ER values and that
      the molecular size and lipophilicity must be well balanced. In the studied
      enhancers having the same chain length, the enhancement activity is dependent
      only on their permeability coefficients. This finding confirms the Warner's
      hypothesis that the polar head of an enhancer is responsible for the permeation
      and anchoring of the molecule into the stratum corneum lipids and that it does
      not influence the mechanism of action. For the specific action of enhancers, that
      is disordering of the intercellular lipid packing, the length of the hydrophobic
      chain(s) and not the lipophilicity is important. Furthermore, the examination of
      the FTIR spectra indicated that the most active substances possess the most
      ordered chains. The described relationships could bring more rational approaches
      in designing new potent enhancers for transdermal formulations.

PMID- 14642583
TI  - 4-alkylidene-azetidin-2-ones: novel inhibitors of leukocyte elastase and
      gelatinase.
AB  - In addition to their antibiotic potency, beta-lactams have recently been
      investigated as inhibitors of serine proteinase such as leukocyte elastase (LE),
      released by inflammatory cells. We describe the synthesis of a series of 4
      alkylidene-beta-lactams, and investigate how substitutions on C-3, C-4, and N-1
      of the beta-lactam ring affect the activity of human LE and gelatinases MMP-2 and
      MMP-9. LE activity was measured using a chromogenic substrate, while gelatin
      zymography assay was used to evaluate gelatinase activity. We demonstrate that C
      4 unsaturation on the beta-lactam ring determines the degree of biological
      activity, with a selectivity over LE by 3-[1-(tert-butyldimethylsilyloxy)-ethyl]
      derivatives (lowest IC(50) was 4 microM), and over gelatinase MMP-2 by C-3
      unsubstituted 4-[1-ethoxycarbonyl]-ethylidene-beta-lactams (lowest IC(50) was 60
      microM). (3S)-3-[(1R)-1-hydroxyethyl]-4-(1-ethoxycarbonyl)-ethylidene-azetidin-2
      one inhibits gelatinase MMP-9. The compounds tested showed no cytotoxicity
      against NIH-3T3 murine fibroblasts. This is the first example of beta-lactams
      inhibiting metallo-proteinases instrumental in cancer invasion and angiogenesis.
      These molecules are good candidates for prototype drugs showing selective
      antibiotic, anti-inflammatory, and anti-invasion properties.

PMID- 14642584
TI  - Synthesis, radiosynthesis and in vivo evaluation of 5-[3-(4-benzylpiperidin-1
      yl)prop-1-ynyl]-1,3-dihydrobenzoimidazol-2-[(11)C]one, as a potent NR(1A)/2B
      subtype selective NMDA PET radiotracer.
AB  - Recently, a new series of potent and highly subtype-selective 1
      (heteroarylalkynyl)-4-benzylpiperidine antagonists of the NMDA receptors has been
      described by Pfizer Laboratories. In this series, 5-[3-(4-benzylpiperidin-1
      yl)prop-1-ynyl]-1,3-dihydrobenzoimidazol-2-one (1) was identified as a selective
      antagonist for the NR1(A)/2B subtype, displaying IC(50) values for inhibition of
      the NMDA responses of 5.3 nM for this subtype (compared to NR1(A)/2A: 35 microM
      and NR1(A)/2C>100 microM) and was active in rat at a relatively low dosage
      (10mg/kg po). Derivative 1 has been synthesized in four chemical steps in good
      overall yield and labelled with carbon-11 at its benzoimidazolone ring using
      [(11)C]phosgene. The pharmacological profile of [(11)C]-1 was evaluated in vivo
      in rats with biodistribution studies and brain radioactivity monitored with
      intracerebral radiosensitive beta-microprobes. The brain uptake of [(11)C]-1 was
      extremely low (0.07% I.D./mL on average at 30 min) and rather uniform across the
      different brain structures. This in vivo brain regional distribution of [(11)C]-1
      did not match with autoradiographic or binding data obtained with other NR2B
      subtype-selective NMDA ligands. Competition studies with ifenprodil (20 mg/kg,
      ip, 30 min before the radiotracer injection) failed to demonstrate specific
      binding of the radiotracer in the brain. In view of these results, and especially
      considering the low brain penetration of the radiotracer, [(11)C]-1 does not have
      the required properties for imaging NMDA receptors using positron emission
      tomography.

PMID- 14642585
TI  - Indolizines as novel potent inhibitors of 15-lipoxygenase.
AB  - 15-Lipoxygenase (15-LO) has been implicated in oxidation of low-density
      lipoproteins (LDL) and this enzyme may be involved in the development of
      atherosclerosis. We have examined 1-substituted indolizines as possible
      inhibitors of 15-LO from soy beans and from rabbit reticulocytes. Most compounds
      studied were significantly more active as inhibitors of 15-LO from soy beans than
      quercetin. The indolizines were slightly less potent inhibitors of the mammalian
      enzyme, but we found good correlation between inhibitory activity against both 15
      LO enzymes studied. Several of the compounds were only weak DPPH scavengers and
      they may therefore be regarded as so-called non antioxidant inhibitors of 15-LO.

PMID- 14642586
TI  - Rat brain guanosine binding site. Biological studies and pseudo-receptor
      construction.
AB  - Rat brain guanosine binding sites were studied by (i). a pharmacological approach
      to confirm the hypothesis of the existence of specific G-coupled receptors for
      guanosine (1) and, for the first time, delineate a structure-activity
      relationship for a series of guanosine derivatives; (ii). a molecular modelling
      approach to design a pseudo-receptor construction. GTP and its non-hydrolysable
      analogue Gpp[NH]p decreased [3H]-guanosine binding to rat brain membranes.
      Gpp[NH]p 30 and 100 microM induced a dose-dependent decrease in [3H]-guanosine
      affinity and PTX pretreatment of rat brain membranes caused a 50% reduction in
      binding. In slices from rat brain cortex, guanosine induced a dose-dependent
      increase in intracellular cAMP. This increase is specific for guanosine, since
      neither the pretreatment with adenosine deaminase nor the A(1) and A(2) adenosine
      receptor antagonists were able to modify the guanosine-induced cAMP accumulation.
      The structure-activity relationship showed that the potency order of the best
      substances able to displace 50 nM [3H]-guanosine was guanosine (1)=6
      thioguanosine (3)>8-bromoguanosine (4)>inosine (10)>7-methylguanosine (6)=3'
      deoxyguanosine (9)>2'-deoxyguanosine (8)=guanine (11)=6-thioguanine (12)>>N(2)
      methylguanosine (5). The competition studies confirmed that [3H]-guanosine site
      was distinct from the well characterized ATP and adenosine binding sites. The
      present results are rationalized in terms of a putative pseudo-receptor construct
      which includes all the relevant physicochemical interaction between guanosine
      analogues and their putative binding sites. This construct will be useful for the
      in silico screening of compound libraries in search for new potent and
      structurally diverse pharmacological tools.

PMID- 14642587
TI  - Novel naphthalimide hydroperoxide photonucleases: the role of thiocyclic-fused
      area and the difference in spectra, photochemistry and photobiological activity.
AB  - Novel five- and six-membered thiocyclic-fused naphthalimide hydroperoxides (7, 8)
      as photonucleases were designed, synthesized via unusual isomerization in Pschorr
      cyclization and photooxygenation. The five-membered 7 was able to induce single
      strand nicks in duplex DNA pH independently (7.0-8.5) at 0.5 microM under 366 nm,
      while the six-membered 8 could photonick the duplex DNA pH dependently (7.0-8.5)
      at 5 microM under 450 nm and showed 'time-controlled' photo-bioactivity. Their
      thiocycles and the angular conjugated plane have contributions to their binding
      affinity with DNA and photocleaving efficiency.

PMID- 14642588
TI  - Synthesis and opioid activity of N,N-dimethyl-Dmt-Tic-NH-CH(R)-R' analogues:
      acquisition of potent delta antagonism.
AB  - N,N-Dimethylation of the H-Dmt-Tic-NH-CH(R)-R' series of compounds produced no
      significant affect on the high delta-opioid receptor affinity (K(i)=0.035-0.454
      nM), but dramatically decreased that for the micro-opioid receptor. The effect of
      N-methylation was independent of the length of the linker (R); however, the
      bioactivities were affected by the chemical composition of the third aromatic
      group (R'): phenyl (Ph) (5'-8') elicited a greater reduction in micro-affinity
      (40-70-fold) compared to analogues containing 1H-benzimidazole-2-yl (Bid) (9
      fold). The major consequences of N,N-dimethylation on in vitro bioactivity were:
      (i). a loss of delta-agonism coupled with the appearance of potent delta
      antagonism (4'-7') (pA(2)=8.14-9.47), while 1 exhibited only a 160-fold decreased
      delta agonism (1') and the delta antagonism of 8 enhanced >10-fold (pA(2)=10.62,
      8'); and (ii). a consistent loss of micro-affinity resulted in enhanced delta
      opioid receptor selectivity. With the exception of compound 1', the change in the
      hydrophobic environment at the N-terminus and formation of a tertiary amine by
      N,N-dimethylation in analogues of the Dmt-Tic pharmacophore produced potent delta
      selective antagonists.

PMID- 14642589
TI  - Enhanced antitumor activity [correction for activitiy] of trans(+/-)-1,2
      diaminocyclo- hexaneglutamatoplatinum(II) formulated with stealth liposome.
AB  - The antitumor platinum(II) compound, [Pt(dach)(Glu)] (dach=trans(+/-)-1,2
      diaminocyclohexane, Glu=glutamate) was formulated with a stealth liposome to
      improve its biological activity. Liposomes were composed of PC/PEG2000-PE/CH
      (PC=1,2-diacyl-glycero-3-phosphocholine; PEG2000-PE=poly(ethylene glycol)2000-1,2
      diacyl-glycero-3-phosphoethanolamine; CH=cholesterol) involving different acyl
      moieties of phospholipids such as DO (dioleoyl), DM (dimyristoyl) or DS
      (distearoyl) group. Among the different acyl groups in the stealth liposomes, the
      DM formulation was optimal for the preparation of the liposomal [Pt(dach)(Glu)]
      at the mole ratio of DMPC/PEG2000-DMPE/CH=50/5/45 and at the weight ratio of
      drug/lipid=1/20, which is represented as L-[Pt(dach)(Glu)]. In vitro cytotoxicity
      was examined in sensitive A2780 and ME180 and their cisplatin-resistant A2780/PDD
      and ME180/PDD cancer cells. L-[Pt(dach)(Glu)] was 2 approximately 3 times more
      cytotoxic than the free complex [Pt(dach)(Glu)] and cisplatin in sensitive cells,
      and 4 approximately 8 times more cytotoxic in resistant cells. Thus, the
      resistance index of L-[Pt(dach)(Glu)] was 1.3 approximately 2 while those of the
      free complex and cisplatin were 5 approximately 6, which indicates that L
      [Pt(dach)(Glu)] overcome the cisplatin resistance in both resistant cells. In
      vivo antitumor activity was assayed against the L1210/S leukemia. The optimal
      activities (% T/C) of the free complex and L-[Pt(dach)(Glu)] were >459/20 and
      >442/200 mg/kg, respectively. Considering the amount of the platinum complex in L
      [Pt(dach)(Glu)], the liposomal [Pt(dach)(Glu)] displayed 2-fold higher drug
      potency than the free complex. The biodistribution experiment using LE52 tumor
      bearing mouse showed excellent lung targeting property of L-[Pt(dach)(Glu)].

PMID- 14642590
TI  - Novel 6-hydroxy-3-morpholinones as cornea permeable calpain inhibitors.
AB  - A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and
      the hydroxy group of P(2) site form a cyclic hemiacetal, was identified as
      calpain inhibitors. The placement of isobutyl group at the 2-position of the 3
      morpholinone was the most effective modification for inhibiting micro- and m
      calpains. Substitutions of benzyl at the 5-position in the S-configuration had
      virtually no effect on inhibitory activity. Several compounds showed appreciable
      selectivity for calpains over cathepsin B. NMR experiments demonstrated that the
      representative 6-hydroxy-3-morpholinone 10a (SNJ-1757) was more stable to
      nucleophilic attack than the corresponding aldehyde inhibitor 24. Furthermore, 6
      hydroxy-3-morpholinone 10a proved to have better corneal permeability than
      aldehyde inhibitor 24 in an in vitro experiment.

PMID- 14642591
TI  - Cyclic phosphinamides and phosphonamides, novel series of potent matrix
      metalloproteinase inhibitors with antitumour activity.
AB  - The design, synthesis, and structure-activity relationship (SAR) of a series of
      novel nonpeptidic cyclic phosphon- and phosphinamide-based hydroxamic acids as
      inhibitors of matrix metalloproteinases MMP-1, MMP-3, and MMP-9 are presented.
      Based on modelling studies and X-ray analysis, a model of the binding mode of
      these novel compounds in the MMP active site was obtained. This model provided a
      rational explanation for the observed SAR data, which included a systematic study
      of different S1' directed substituents, zinc-complexing groups, chirality, and
      variation of the cyclic phosphon- and phosphinamide rings. The in vivo effect of
      four compounds in a human fibrosarcoma mouse model (HT1080) was evaluated and
      compared to that of a reference compound, Prinomastat. Inhibition of tumour
      growth was observed for all four compounds.

PMID- 14642592
TI  - Heterocyclic rimantadine analogues with antiviral activity.
AB  - 2-(1-Adamantyl)pyrrolidines 6, 7, 2-(1-adamantyl)piperidines 10, 12a-c, 15a,b and
      2-(1-adamantyl)hexahydroazepines 19, 21, 22 were synthesized and tested for their
      antiviral activity against influenza A, B viruses and the human immunodeficiency
      virus type 1 (HIV-1) and type 2 (HIV-2). The synthetic procedure followed for the
      preparation of the parent piperidine 10 represents a general method for the
      synthesis of 2-alkyl- or cycloalkyl-substituted piperidine alkaloids. Parent
      aminoadamantanes 6, 10 and 19 contain the 1-aminoethyl pharmacophore group of
      rimantadine drug 2, extended into a saturated nitrogen heterocycle: pyrrolidine,
      piperidine and hexahydroazepine, respectively. The ring size effect in anti
      influenza A activity was investigated. Rimantadine analogues 6 and 10 were,
      respectively, 6- and 4-fold more active than the drug Rimantadine 2, whereas the
      hexahydroazepine derivative 19 was inactive. Thus, enlargement from a 5
      (pyrrolidine)- or 6-(piperidine)- to a 7-(hexahydroazepine)- membered
      heterocyclic ring dramatically reduced the anti-influenza virus A activity.
      Substitution of piperidine 10 with a dialkyaminoethyl group led to the active
      compounds 15a and 15b: compound 15a was active against influenza A virus whereas
      both 15a and 15b were active against HIV-1.

PMID- 14642593
TI  - QSAR study on some pyridoacridine ascididemin analogues as anti-tumor agents.
AB  - Pyridoacridine ascididemin analogues have been reported as anticancer agents for
      their interesting antitumor activity against human cancer cells. A quantitative
      structure-activity relationship (QSAR) analysis of ascididemin analogues was
      attempted using the physicochemical parameters and the electrotopological state
      atom (ETSA) indices. This study indicates that the electron withdrawing
      substituents with higher MR (molar refractivity) value at R(1) position favor the
      anti-tumor activity and the presence of NHR (R is hydrogen or alkyl group) at the
      R(3) position has contribution to the anti-tumor activity. ETSA indices have been
      incorporated as independent variable in the QSAR model with physicochemical
      parameters. It clearly suggests the importance of atoms 2, 3, 4, 5, 6 and 7 to
      the anti-tumor activity.

PMID- 14642594
TI  - Synthesis and structure-activity relationships of 2-amino-8-hydroxyadenines as
      orally active interferon inducing agents.
AB  - Recently, we have reported the 8-hydroxyadenine derivatives (2-4) as a novel
      class of interferon (IFN) inducing agents. In the present study, a series of 8
      hydroxyadenines, which possess various amino moieties at the adenine C(2)
      position, were synthesized and evaluated for their ability to induce endogenous
      IFN in comparison to the known active agent, Imiquimod. Among the compounds
      prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of
      adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o
      induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of
      Imiquimod, and showed a good oral bioavailability (F=81%).

PMID- 14642596
TI  - QSAR study on 5-lipoxygenase inhibitors using distance-based topological indices.
AB  - QSAR study on a large set of 5-lipoxygenase inhibitors has been carried out using
      distance-based topological indices. Regression analysis of the data has indicated
      that an excellent model is obtained when these topological indices are combined
      with some classical molecular descriptors. The obtained models are critically
      discussed and examined.

PMID- 14642595
TI  - Synthesis of 4-amino-6-(hetero)arylalkylamino-1,2,4-triazolo[4,3-a]quinoxalin-1
      one derivatives as potent A(2A) adenosine receptor antagonists.
AB  - In previous papers (Colotta, V. et al. Arch. Pharm. Pharm. Med. Chem. 1999, 332,
      39. Colotta, V. et al. J. Med. Chem. 2000, 43, 1158) we reported the synthesis
      and binding affinity at bovine (b) A(1) and A(2A) and human (h) A(3) adenosine
      receptors (ARs) of the 4-amino-6-benzylamino-2-phenyl-1,2,4-triazolo[4,3
      a]quinoxalin-1-one (compound A) which resulted in a potent and selective A(2A) AR
      antagonist. Compound A provided the lead compound of a series of 6- or 8
      (hetero)arylalkylamino-4-amino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one
      derivatives (compounds 1-20) which are the object of this paper. Most of the
      newly synthesized compounds are inactive at hA(3) ARs while they possess both
      nanomolar bA(2A) affinities and different degrees of bA(2A) versus bA(1)
      selectivity. The binding data show that hydrophilic substituents on the benzyl
      moiety are the most profitable for bA(2A) receptor affinity. Furthermore, their
      steric hindrance seems to play an important role for the bA(2A) AR interaction,
      thus suggesting that the 6-aralkylamino moiety of these ligands interacts with a
      size-limited binding pocket of this AR subtype. Thus, the SAR studies provided us
      some new insights about the structural requirements of the bA(2A) AR recognition
      site.

PMID- 14642597
TI  - 1,2,4-thiadiazole: a novel Cathepsin B inhibitor.
AB  - A novel class of Cathepsin B inhibitors has been developed with a 1,2,4
      thiadiazole heterocycle as the thiol trapping pharmacophore. Several compounds
      with different dipeptide recognition sequence (i.e., P1'-P2'=Leu-Pro-OH or P2
      P1=Cbz-Phe-Ala) at the C5 position and with different substituents (i.e., OMe,
      Ph, or COOH) at the C3 position of the 1,2,4-thiadiazole ring have been
      synthesized and tested for their inhibitory activities. The substituted
      thiadiazoles 3a-h inhibit Cat B in a time dependent, irreversible manner. A
      mechanism based on active-site directed inactivation of the enzyme by disulfide
      bond formation between the active site cysteine thiol and the sulfur atom of the
      heterocycle is proposed. Compound 3a (K(i)=2.6 microM, k(i)K(i)=5630 M(-1)s(-1))
      with a C3 methoxy moiety and a Leu-Pro-OH dipeptide recognition sequence, is
      found to be the most potent inhibitor in this series. The enhanced inhibitory
      potency of 3a is a consequence of its increased enzyme binding affinity (lower
      K(i)) rather than its increased intrinsic reactivity (higher k(i)). In addition,
      3a is inactive against Cathepsin S, is a poor inhibitor of Cathepsin H and is
      >100-fold more selective for Cat B over papain.

PMID- 14642598
TI  - Discovery of 2-phenyl-3-sulfonylphenyl-indole derivatives as a new class of
      selective COX-2 inhibitors.
AB  - 2-Sulfonylphenyl-3-phenyl-indole derivatives have been reported to be highly
      potent and selective COX-2 inhibitors previously. In this paper, the regio
      isomeric analogues-2-phenyl-3-sulfonylphenyl-indoles were identified as potent
      and selective COX-2 inhibitors. This work led to the discovery of compounds 4a
      and 8a possessing higher activity than Celecoxib on cellular assay.

PMID- 14642599
TI  - Comparative molecular field analysis and QSAR on substrates binding to cytochrome
      p450 2D6.
AB  - In this study, we utilized comparative molecular field analysis (CoMFA) to gain a
      better understanding of the steric and electrostatic features of the cytochrome
      p450 2D6 (CYP2D6) active site. The training set consists of 24 substrates with
      reported K(M) values from liver microsomal CYP2D6 spanning an activity range of
      almost three log units. The low energy conformers were fit by root mean square
      (RMS) to minaprine at the site of metabolism and to the protonated nitrogen. In
      this manner, we constructed two CoMFA models, one model with a distance
      constraint and another without. The model with the distance parameter (non-cross
      validated R(2)=0.99) was approximately equal to the CoMFA without a distance
      parameter (non-cross-validated R(2)=0.98). Validation of our CoMFA was
      accomplished by predicting the K(M) values of 15 diverse CYP2D6 substrates not in
      the original training set resulting in a predictive R(2)=0.62. Finally, we also
      pursued correlations of pK(a) and log P with CYP2D6 substrate K(M) in an effort
      to investigate other physicochemical properties.

PMID- 14642600
TI  - A novel series of complexones with bis- or biazole structure as mixed ligands of
      paramagnetic contrast agents for MRI.
AB  - We describe the syntheses, physicochemical properties and biological evaluation
      of a novel series of complexones containing bis- or biazoles moieties and two
      iminodiacetic acid units as novel ligands for paramagnetic lanthanides. The
      complexones were prepared by reaction of the corresponding 1,1'-bishaloethylbi-
      or bispyrazoles with methyl iminodiacetate and subsequent NaOH hydrolysis. 1,1'
      Bisbromoethyl precursors were obtained by direct alkylation with an excess of 1,2
      dibromoethane, or by heating the corresponding alcohol in HCl. Sigmoidal binding
      isotherms and MO calculations supported as most stable structures in solution,
      those containing two Gd(III) atoms bound per molecule of complexone with half
      saturation values S(0.5) (M(-1), 22 degrees C, pH 7.2) in the range 6.5 10(
      6)<S(0.5)<36.1 10(-6). Relaxivity properties [r(1), r(2), s(-1) mM(-1) Gd(III)]
      determined at 1.5 Tesla gave values (12.0<r(1)<17.7, 12.2<r(2)<20), improving
      significantly the relaxivities of reference compounds such as Gd(III)EDTA (5.2,
      5.6) or Gd(III)DTPA (4.30, 4.30). These improvements involve mainly increased
      hydration and slower rotational motions. In vitro toxicity experiments are
      reported.

PMID- 14642602
TI  - Evolution of liver transplantation for hepatocellular carcinoma.

PMID- 14642603
TI  - Cardiovascular complications in liver diseases.

PMID- 14642604
TI  - Extensive changes in liver gene expression induced by hereditary tyrosinemia type
      I are not normalized by treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3
      cyclohexanedione (NTBC).
AB  - BACKGROUND: Hereditary Tyrosinemia type I, caused by deficiency of
      fumarylacetoacetate hydrolase (FAH), is characterized by liver and kidney damage.
      Administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione
      (NTBC) corrects the tyrosinemia phenotype, but does not prevent development of
      hepatocellular carcinoma. AIM: To gain insight into the pathophysiological
      changes associated with liver damage induced by tyrosinemia and the preventive
      action of NTBC on these changes. METHODS: Differential gene expression patterns
      in livers of tyrosinemia-affected and healthy mice, and of tyrosinemia-affected
      and NTBC-treated Fah-/- mice were investigated by suppression subtractive
      hybridization. RESULTS: Transcripts encoding proteins playing a role in protein
      turnover, growth and proliferation, RNA processing, and signal transduction were
      primarily induced in tyrosinemia-affected livers. Transcripts mainly contributing
      to the profile of suppressed genes encode proteins that are secreted by the
      liver, or are necessary for intermediate metabolism. NTBC treatment fails to
      normalize the tyrosinemia-induced alterations in expression of transcripts
      encoding proteins involved in protein turnover, signal transduction, and cell
      growth and proliferation. CONCLUSIONS: The failure of NTBC to normalize liver
      gene expression of Fah-/- mice may play a role in rendering the tyrosinemia
      affected liver susceptible to development of hepatocellular carcinoma under NTBC
      treatment.

PMID- 14642605
TI  - Specific, functional effector/memory CD8+ T cells are found in the liver post
      vaccination.
AB  - BACKGROUND: The liver efficiently eliminates activated CD8+ T blasts. It is
      unknown if vaccine-primed CD8+ T blasts migrate to and establish functional CD8+
      T cell immunity in the liver post-immunization. AIMS: We tested, if functional
      CD8+ T cell populations can be detected in the liver post-vaccination. METHODS:
      Murine CD8+ T cells with different epitope/restriction specificities were primed
      by intramuscular injection of protein- or DNA-based vaccines. The kinetics of
      appearance in the liver, as well as the surface phenotype and functional
      competence of intrahepatic, specific CD8+ T cell populations was tested. RESULTS:
      High numbers of specific CD8+ T cells appear in the liver after vaccination that
      are activated (CD69+ CD44+), express effector functions (CD27lo/CD28lo phenotype,
      interferon gamma secretion, specific cytolytic reactivity), but show no evidence
      of apoptosis (annexin V-, B220lo, similar numbers/kinetics in primed, congenic
      lpr/lpr mice). Specific CD8+ T cells from the liver adoptively transferred into a
      naive, syngeneic host successfully reconstitute specific CD8+ T cell immunity.
      CONCLUSIONS: Specific, functionally competent CD8+ effector/memory T cell
      populations are established in the liver for months post-vaccination.

PMID- 14642606
TI  - Preferential accumulation of CD103+ T cells in human livers; its association with
      extrathymic T cells.
AB  - BACKGROUND/AIMS: CD103, a mucosal integrin alphaEbeta7, binds to E-cadherin
      expressed on hepatocytes and bile duct epithelium in the liver. Although CD103+ T
      cells are enriched in intestinal intraepithelial lymphocytes, the localization of
      those cells in the liver is unknown. METHODS: We investigated whether CD103+
      cells are present in human livers, and how they are associated with the
      intrahepatic development of T cells by flow cytometry and immunohistochemistry.
      RESULTS: Human livers contain significantly (P<0.001) higher percentages of
      CD103+ cells in CD4+ and CD8+ T cells (25.7+/-13.5 and 27.1+/-19.3%,
      respectively) than peripheral blood lymphocytes. Moreover, CD103+ cells in the
      liver, but not in peripheral blood, contained T cells with intermediate
      expression level of T cell receptor alphabeta. Those cells consist of mostly CD4+
      and CD4-CD8- cells, and expressed low level of CD56 and interleukin-2 receptor
      beta chain in most of the population. These characteristics are distinct from
      natural killer T cells, which have been thought to be extrathymic T cells in
      human livers. Moreover, intrahepatic CD103+ cells expressed mRNA for
      recombination-activating gene-1, -2 and pre T cell receptor-alpha detected by
      reverse transcription-polymerase chain reaction. CONCLUSIONS: CD103+ T cells are
      preferentially accumulated in human livers, and those T cells show
      characteristics of extrathymic T cells.

PMID- 14642607
TI  - Haemochromatosis-associated HFE genotypes in English blood donors: age-related
      frequency and biochemical expression.
AB  - BACKGROUND/AIMS: There are limited data on the frequency and biochemical
      expression of the haemochromatosis-associated mutations C282Y and H63D in healthy
      people. METHODS: We genotyped (bi-directional PCR amplification of specific
      alleles method) and performed serum iron studies in randomly selected English
      male blood donors (<4 previous units donated) in four age bands <30, 30-40, 40-50
      and >50 years. RESULTS: In 6261 subjects, frequency of C282Y homozygosity (+/+)
      was 0.3%, C282Y/H63D compound heterozygosity (+/-) 2.0%, and H63D and C282Y
      heterozygosity +/-, 21.7 and 10.4%, respectively. Genotype distribution was
      within Hardy-Weinberg equilibrium in each age band. C282Y +/- frequency fell from
      11.7% in subjects <30 years to 8.2% in subjects >50 (Chi2 7.19; P<0.005). No such
      trend was seen for C282Y +/+. In C282Y +/+ subjects, median serum ferritin was
      247 (range 60-2449) microg/l and exceeded >500 microg/l in only two of 18
      subjects. Compared to wild/wild (-/-) subjects, C282Y and H63D +/- subjects had
      slightly higher serum iron and lower unsaturated iron binding concentrations,
      similar overall serum ferritin values but higher serum ferritin values in
      subjects who had previously donated blood. CONCLUSIONS: C282Y +/+ shows limited
      biochemical expression and no trend towards age-related attrition. C282Y and H63D
      +/- may protect against iron deficiency.

PMID- 14642608
TI  - NCX-1000, a nitric oxide-releasing derivative of ursodeoxycholic acid,
      ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic
      resistance in the isolated and perfused rat liver.
AB  - BACKGROUND/AIMS: We studied whether acute administration of NCX-1000, a nitric
      oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), to animals with
      established liver cirrhosis decreases intrahepatic resistance and modulates
      hepatic vascular hypereactivity to norepinephrine (NE). METHODS: Four-week bile
      duct ligated (BDL) cirrhotic and control, sham-operated, rats were treated orally
      with 28 mg/kg per day NCX-1000 or 15 mg/kg per day UDCA for 5 days. Isolated
      normal and cirrhotic livers were perfused with NE, from 10 nM to 30 microM, in a
      recirculating system. RESULTS: NCX-1000 administration to BDL cirrhotic rats
      decreased portal pressure (P<0.01) without affecting mean arterial pressure and
      heart rate. In the isolated perfused liver system, administration of NE resulted
      in a dose-dependent increase of intrahepatic resistance. Vasoconstriction caused
      by 30 microM NE was reduced by 60% in animals treated with NCX-1000 (P<0.001),
      while UDCA was uneffective. The same portal pressure lowering effect was
      documented in cirrhotic and sham operated rats. Administration of NCX-1000 to BDL
      and sham operated rats resulted in a similar increase of nitrite/nitrate and cGMP
      concentrations in the liver. CONCLUSIONS: By selectively delivering NO to the
      liver, NCX-1000 increases cGMP concentrations and effectively counteracts the
      effect of endogenous vasoconstrictors on the hepatic vascular tone.

PMID- 14642609
TI  - A liver-specific nitric oxide donor improves the intra-hepatic vascular response
      to both portal blood flow increase and methoxamine in cirrhotic rats.
AB  - BACKGROUND/AIMS: A decreased intra-hepatic nitric oxide (NO) production
      participates on the pathogenesis of portal hypertension in cirrhosis. We tested
      the hemodynamic effects of a liver-specific NO donor (NCX-1000) derived from
      ursodeoxycholic acid in portal hypertensive cirrhotic rats. METHODS: After a 14
      day treatment with ursodeoxycholic acid or NCX-1000 by gavage, ascitic cirrhotic
      rats (CCl4-induced) were used in two studies: (1) in vivo mean arterial pressure
      (MAP), portal pressure (PP) and superior mesenteric artery (SMA) blood flow
      measurements before and during progressive blood volume expansion (blood
      infusion); and (2) in situ liver perfusion to obtain dose/response curves to
      methoxamine (alpha1-adrenergic agonist) and flow/pressure curves. RESULTS: Basal
      heart rate, MAP, and PP were similar in both groups. During blood infusion,
      similar MAP and SMA flow increases were observed in both groups; however, PP
      increase observed in control rats was blunted in NCX-1000 treated rats (P=0.015).
      In liver perfusions, flow/pressure curves were similar in both groups; however,
      NCX-1000-treated livers showed a lower response to methoxamine (P=0.016). cGMP
      concentration in NCX-1000-treated livers was higher (P=0.015) than in controls.
      CONCLUSIONS: Treatment with a liver-specific NO donor improves the portal system
      adaptability to portal blood flow increase and ameliorates the intra-hepatic
      response to methoxamine in cirrhotic rats.

PMID- 14642610
TI  - Improvement of prognostic power of the Child-Pugh classification of liver
      cirrhosis by hyaluronan.
AB  - BACKGROUND/AIMS: Modifications of the Child-Pugh classification of liver
      cirrhosis by incorporation of hyaluronan were tested to improve the prognostic
      power for long term evaluation of liver cirrhosis in 126 patients observed over a
      period of 10 years. METHODS: Serum concentrations of HA were determined at study
      entry. Statistical analysis included Kaplan-Meier life tables and stepwise
      multivariant Cox-regression analysis for each parameter of Child-Pugh
      classification and hyaluronan. Prognostic models were developed by exchanging
      prothrombin time, albumin and encephalopathy by HA in different combinations.
      RESULTS: Based on a good single correlation between hyaluronan (0.62) and
      clinical course (P<0.01) we conclude that models with hyaluronan instead of
      albumin or encephalopathy and with or without shifted threshold values of
      bilirubin and albumin are superior for the prediction of the long term prognosis.
      In Cox-regression analysis, apart from hyaluronan and bilirubin, no other
      parameters contributed to an improvement. CONCLUSIONS: We conclude that a
      modification of the Child-Pugh classification of liver cirrhosis by inclusion of
      HA significantly improves the predictive power of CP, especially in alcoholic
      etiology. A prospective validation of the newly defined scores needs to be done
      in the future.

PMID- 14642611
TI  - Hemostatic effect of activated recombinant factor VII (rFVIIa) in liver disease:
      studies in an in vitro model.
AB  - BACKGROUND/AIMS: There is clinical evidence for the efficacy of activated
      recombinant factor VII (rFVIIa) in patients with cirrhosis. The exact mechanism
      of action of rFVIIa in this clinical condition is unknown. We have explored
      effects of rFVIIa on hemostasis in cirrhotic patients using an in vitro perfusion
      technique. METHODS: Blood samples were drawn from control donors or from 11
      patients previously diagnosed with cirrhosis (seven Child-Pugh B and four Child
      Pugh C) and anticoagulated with low molecular weight heparin. rFVIIa was added to
      blood samples at therapeutic concentrations (0.5 or 1 microg/ml of plasma) and
      blood was recirculated through annular chambers containing damaged vascular
      segments. Presence of platelets and fibrin on the subendothelium were
      morphometrically quantified. RESULTS: Cirrhotic patients showed a diminished
      platelet interaction with the subendothelium compared to healthy donors (17.3%
      (9.28-28.88%) vs. 26.16% (19.96-54.5%), P<0.05). After addition of rFVIIa to
      cirrhotic samples, no differences in platelet covered surface were observed.
      However, fibrin formation was significantly improved after the addition of rFVIIa
      (from 51.81% (3.02-86.68%) to 86.94% (30.03-93.18%) and 89.05% (45.65-93.84%),
      respectively, P<0.05). CONCLUSIONS: Our data confirm a defective interaction of
      platelets with the subendothelium in cirrhotic patients. rFVIIa improved local
      fibrin formation at damaged sites and this mechanism could explain the beneficial
      action of rFVIIa in cirrhotic patients.

PMID- 14642612
TI  - Apoptosis of hepatic stellate cells in carbon tetrachloride induced acute liver
      injury of the rat: analysis of isolated hepatic stellate cells.
AB  - BACKGROUND/AIMS: Analysis of isolated hepatic stellate cells (HSCs) from the
      injured liver may provide direct information on HSC apoptosis. However, it has
      not been established whether apoptotic HSCs would be isolated using the usual
      density gradient centrifugation method. The aim of this study was to observe the
      serial pattern of proliferation and apoptosis in isolated HSCs in comparison with
      that of liver tissue sections in CCl4 induced acute liver injury. METHODS: Male
      Sprague-Dawley rats were treated with a single intraperitoneal injection of
      carbon tetrachloride (CCl4) and were killed at various time points after the
      treatment. RESULTS: HSC proliferation showed a maximal increase at 32 h after
      CCl4 injection. Apoptosis of HSC, examined by quantitative analysis of annexin-V
      fluorescein isothiocyanate (FITC)staining, showed the maximal increase at 64 h.
      Apoptosis of HSC in liver tissue sections examined by counting desmin and Tdt
      mediated-dUTP biotin nick end labeling (TUNEL) double staining cells, peaked at
      64 h. The number of TUNEL positive HSCs in liver tissue sections correlated
      significantly with annexin-V-FITC binding of isolated HSC. CONCLUSIONS: Studying
      apoptosis using apoptotic HSCs isolated by a usual density gradient
      centrifugation method from injured tissue sections would be feasible since it
      correlated with in vivo apoptosis of HSC.

PMID- 14642613
TI  - Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in the severely
      obese.
AB  - BACKGROUND/AIMS: Insulin resistance and systemic hypertension are predictors of
      advanced fibrosis in obese patients with non-alcoholic fatty liver disease
      (NAFLD). Genetic factors may also be important. We hypothesize that high
      angiotensinogen (AT) and transforming growth factor-beta1 (TGF-beta1) producing
      genotypes increase the risk of liver fibrosis in obese subjects with NAFLD.
      METHODS: One hundred and five of 130 consecutive severely obese patients having a
      liver biopsy at the time of laparoscopic obesity surgery agreed to have genotype
      analysis. Influence of specific genotype or combination of genotypes on the stage
      of hepatic fibrosis was assessed after controlling for known risk factors.
      RESULTS: There was no fibrosis in 70 (67%), stages 1-2 in 21 (20%) and stages 3-4
      fibrosis in 14 (13%) of subjects. There was no relationship between either high
      AT or TGF-beta1 producing genotypes alone and hepatic fibrosis after controlling
      for confounding factors. However, advanced hepatic fibrosis occurred in five of
      13 subjects (odds ratio 5.7, 95% confidence interval 1.5-21.2, P=0.005) who
      inherited both high AT and TGF-beta1 producing polymorphisms. CONCLUSIONS: The
      combination of high AT and TGF-beta1 producing polymorphisms is associated with
      advanced hepatic fibrosis in obese patients with NAFLD. These findings support
      the hypothesis that angiotensin II stimulated TGF-beta1 production may promote
      hepatic fibrosis.

PMID- 14642614
TI  - Sub-lethal oxidative stress triggers the protective effects of ischemic
      preconditioning in the mouse liver.
AB  - BACKGROUND/AIMS: While ischemic preconditioning confers significant protection
      against subsequent prolonged periods of ischemia, the mechanisms triggering
      protection remain speculative. We hypothesize that a sub-lethal oxidative stress
      during ischemic preconditioning induces defense mechanisms preventing subsequent
      lethal injury. METHODS: We used mouse models of partial and total hepatic
      ischemia for 75 min. Ischemic preconditioning consisted of 10-min ischemia and 15
      min reperfusion prior to the prolonged ischemic insult. RESULTS: Tissue levels of
      peroxides increased about three times after 10 min of ischemia and normalized
      within 15 min of reperfusion. This limited oxidative stress during ischemic
      preconditioning prevented the negative effects of subsequent prolonged ischemia
      as assessed by AST-levels, TUNEL-staining of hepatocytes and animal survival. N
      Acetylcysteine inhibited the mild oxidative burst of ischemic preconditioning,
      and fully reversed the protective effects of preconditioning. The protective role
      of a sub-lethal oxidative stress was supported by the benefit of delivery of an
      H2O2-analog through the portal vein prior to a long ischemic insult. This
      challenge conferred similar protection as ischemic preconditioning. CONCLUSIONS:
      We conclude that the mild burst of oxidative stress generated during ischemic
      preconditioning triggers protective mechanisms against subsequent, otherwise
      lethal, ischemic injury. The pathway possibly includes enhancement of natural
      anti-oxidative stress mechanisms.

PMID- 14642615
TI  - Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in
      mice.
AB  - BACKGROUND/AIMS: Hepatic steatosis sensitizes the liver to injury and
      inflammation by unclear mechanisms. Because Fas has been linked to liver injury
      and inflammation, Fas expression and sensitization to Fas signaling was examined
      in models of hepatic steatosis. METHODS: Mice were fed a carbohydrate diet while
      control animals received standard chow. Sensitization to Fas was examined
      following administration of Jo2 antibody. For the in vitro experiments, HepG2
      cells were incubated with or without a mixture of long chain fatty acids (2:1
      oleate:palmitate). Sensitization of the cells to Fas was examined using the CH11
      antibody. RESULTS: Mice fed a high caloric diet developed hepatic steatosis,
      hyperlipidemia, insulin resistance, and hyperleptinemia, all features of the
      human syndrome. Fas expression in hepatocytes was increased as compared to lean
      animals and was coupled to cytotoxic signaling. Indeed, hepatocyte apoptosis,
      liver injury and chemokine generation were all accentuated in obese animals
      following administration of Jo-2, a Fas agonist. Hep G2 cells cultured in the
      presence of free fatty acids also developed 'cellular steatosis', upregulated Fas
      expression and were more sensitive to apoptosis by a Fas agonist. CONCLUSIONS:
      Collectively, these data implicate Fas as a link between obesity associated fatty
      liver and increased susceptibility to liver damage.

PMID- 14642616
TI  - Prometheus--a new extracorporeal system for the treatment of liver failure.
AB  - BACKGROUND/AIMS: Extracorporeal detoxification systems for supportive therapy of
      liver failure have recently gained much interest. We herein report results from
      the first clinical application of Prometheus, a new liver support system in which
      albumin-bound substances are directly removed from blood by special adsorber. In
      a simultaneous step, high-flux hemodialysis is performed. We assessed safety,
      adsorber efficiency and clinical efficacy of the Prometheus system. METHODS:
      Eleven patients with acute-on-chronic liver failure and accompanying renal
      failure were treated with Prometheus on 2 consecutive days for >4 h. RESULTS:
      Prometheus treatment significantly improved serum levels of conjugated bilirubin,
      bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no
      significant changes in hemoglobin and platelet levels, whereas leucocytes
      increased without signs of systemic infection. No treatment-related complications
      except a blood pressure drop in two patients with systemic infection were noted.
      In one patient (Child-Pugh score: 15) Prometheus treatment could not be completed
      due to onset of uncontrolled bleeding 16 h after dialysis. CONCLUSIONS:
      Prometheus is a safe supportive therapy for patients with liver failure. A
      significant improvement of the biochemical milieu was observed already after two
      treatments. Prospective controlled studies with the Prometheus system are
      necessary to evaluate hard clinical end-points.

PMID- 14642617
TI  - Expression of ephrin-B1 in hepatocellular carcinoma: possible involvement in
      neovascularization.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is, in general, a hypervascular
      tumor. Ephrin/Eph molecules have recently been reported as possible regulators of
      angiogenesis. We aimed to clarify the role of ephrin-Bs (B1-B3) in the
      progression of HCC. METHODS: Ephrin-Bs transcripts in 26 HCC and their
      corresponding non-tumor liver tissues were analyzed by the quantitative reverse
      transcription-polymerase chain reaction. We established ephirn-B1 overexpressing
      cell in a human HCC cell line, PLC/PRF/5 cell, and their in vivo growth monitored
      after subcutaneous injection into nude mice. Neovascularization in the inoculated
      tumors was evaluated by the immunohistochemical staining of CD31. The migration
      and proliferation of human umbilical vein endothelial cells (HUVECs) in response
      to soluble ephrin-B1-Fc was examined. RESULTS: The expression of the ephrin-B1
      transcript but not -B2 and -B3 transcripts was significantly higher in HCC
      tissues than in non-tumor tissues (P<0.05). The ephrin-B1 overexpressing cells
      developed tumors more rapidly than controls in vivo (P<0.05), although in vitro
      cell growth was not affected. The tumor vessel number significantly increased in
      the ephrin-B1 overexpressing tumors (P<0.0001). In addition, in vitro studies
      revealed that ephrin-B1 induced migration and proliferation of HUVECs.
      CONCLUSIONS: Ephrin-B1 may be involved in in vivo tumor progression by promoting
      neovascularization in HCC.

PMID- 14642618
TI  - In human hepatocellular carcinoma in cirrhosis proliferating cell nuclear antigen
      (PCNA) is involved in cell proliferation and cooperates with P21 in DNA repair.
AB  - BACKGROUND: Proliferating cell nuclear antigen (PCNA) is a nuclear protein
      involved in DNA-synthesis and repair. During DNA-synthesis and repair the only
      active PCNA fraction is tightly bound to DNA. Similarly, during DNA-repair, a
      fraction of p21 colocalizes with PCNA in a detergent-insoluble form. AIM: The aim
      of the study was to analyze to what extent the presence of DNA-bound PCNA and p21
      correlates with cell proliferation and DNA-repair in hepatocellular carcinoma
      (HCC). METHODS: Twenty-six HCCs and surrounding cirrhosis were studied. The DNA
      bound and detergent-soluble fractions of PCNA and p21 were analyzed by
      immunoblotting. P53 and Ki67-Labeling Index (Ki67-LI) were evaluated by
      immunocytochemistry. RESULTS: Soluble fractions of PCNA and p21 were found in all
      samples. One out of 26 cirrhotic samples displayed a DNA-bound fraction of PCNA
      while no case expressed DNA-bound p21. Fourteen HCCs showed a DNA-bound PCNA
      fraction. A highly significant correlation was found between Ki67-LI and DNA
      bound PCNA but not with detergent-soluble PCNA. DNA-bound p21 and PCNA,
      indicating ongoing DNA repair activity, were present in 6 of these 14 HCCs and
      correlated with a high histological grade and high Ki67-LI. CONCLUSIONS: Our
      results suggest that in HCC PCNA participates both in DNA synthesis and repair
      and that highly proliferating HCCs may display a sustained DNA-repair.

PMID- 14642619
TI  - Molecular features of non-B, non-C hepatocellular carcinoma: a PCR-array gene
      expression profiling study.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) usually develops following
      chronic liver inflammation caused by hepatitis C or B virus. Through expression
      profiling in a rare type of HCC, for which the causes are unknown, we sought to
      find key genes responsible for each step of hepatocarcinogenesis in the absence
      of viral influence. METHODS: We used 68 non-B, non-C liver tissues (20 HCC, 17
      non-tumor, 31 normal liver) for expression profiling with PCR-array carrying 3072
      genes known to be expressed in liver tissues. To select the differentially
      expressed genes, we performed random permutation testing. A weighted voting
      classification algorithm was used to confirm the reliability of gene selection.
      We then compared these genes with the results of previous expression profiling
      studies. RESULTS: A total of 220 differentially expressed genes were selected by
      random permutation tests. The classification accuracies using these genes were
      91.8, 92.0 and 100.0% by a leave-one-out cross-validation, an additional PCR
      array dataset and a Stanford DNA microarray dataset, respectively. By comparing
      our results with previous reports on virus-infected HCC, four genes (ALB, A2M,
      ECHS1 and IGFBP3) were commonly selected in some studies. CONCLUSIONS: The 220
      differentially expressed genes selected by PCR-array are potentially responsible
      for hepatocarcinogenesis in the absence of viral influence.

PMID- 14642620
TI  - Different hepatitis C virus dynamics of free-virions and immune-complexes after
      initiation of interferon-alpha in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: To elucidate the mechanisms of action of interferon (IFN)
      against hepatitis C virus (HCV), we studied the serum HCV dynamics of free
      virions (FV) and immune-complexes (IC) in patients treated with IFN. METHODS: FV
      and IC were separated by immunoprecipitation using anti-human immunoglobulin and
      quantified serially using real-time detection-polymerase chain reaction. RESULTS:
      Initially [1st phase (0-24 h)], the FV decreased more rapidly compared to IC
      [exponential decay slope (EDS)=1.78+/-0.42 vs. 0.99+/-0.31 log10/day, P<0.001;
      half-life=5.65+/-2.02 vs. 12.5+/-2.83 h, P<0.0001], but at the 2nd phase (1-14
      days), half-life of FV was significantly longer than that of IC (101+/-117 vs.
      14.2+/-1.08 h, P<0.005). Regarding response to IFN, the decline slope was not
      significantly different at the 1st phase, but at the 2nd phase, the FV-HCV RNA
      decreased more slowly in non-responders than in sustained responders to IFN
      (EDS=0.05+/-0.02 vs. 0.34+/-0.19 log10/day, P<0.005; half-life=186+/-112 vs.
      15.3+/-1.85 h, P<0.005). CONCLUSIONS: The presence of escape mutants from the
      neutralizing antibodies may be involved in resistance to IFN. Analyzes of FV- and
      IC-HCV dynamics are useful for predicting the IFN efficacy and understanding the
      mechanism of IFN action in chronic hepatitis patients.

PMID- 14642621
TI  - Alcohol and hepatitis C virus core protein additively increase lipid peroxidation
      and synergistically trigger hepatic cytokine expression in a transgenic mouse
      model.
AB  - BACKGROUND/AIMS: Alcohol consumption accelerates the appearance of liver fibrosis
      and hepatocellular carcinoma in patients with chronic hepatitis C virus (HCV)
      infection, but the mechanisms of these interactions are unknown. We therefore
      investigated the effects of chronic ethanol consumption in HCV core protein
      expressing transgenic mice. METHODS: Ethanol was progressively added (up to 20%)
      to the drinking water that was given ad libidum. RESULTS: In vivo fatty acid
      oxidation was not inhibited by ethanol consumption and/or HCV core expression.
      Both chronic ethanol consumption and HCV core expression decreased hepatic
      lipoprotein secretion and caused steatosis, but had no additive effects on
      lipoprotein secretion or steatosis. However, chronic ethanol consumption and HCV
      core protein additively increased lipid peroxidation and acted synergistically to
      increase the hepatic expression of transforming growth factor-beta (TGF-beta)
      and, to a less extent, tumor necrosis factor-alpha (TNF-alpha). CONCLUSIONS: HCV
      core protein expression and chronic alcohol consumption have no effects on in
      vivo fatty acid oxidation and do not additively impair hepatic lipoprotein
      secretion, but additively increase hepatic lipid peroxidation and synergistically
      increase hepatic TNF-alpha and TGF-beta expression. These effects may be involved
      in the activation of fibrogenesis and the development of hepatocellular carcinoma
      in patients cumulating alcohol abuse and HCV infection.

PMID- 14642622
TI  - Dynamics of plasma hepatitis B virus levels after highly active antiretroviral
      therapy in patients with HIV infection.
AB  - BACKGROUND/AIMS: The optimal strategy to prescribe highly active antiretroviral
      therapy (HAART) in patients infected with both hepatitis B virus (HBV) and human
      immunodeficiency virus (HIV) remains unsettled. This study aimed to compare the
      HBV dynamics between HBeAg-positive and HBeAg-negative coinfected patients
      treated with lamivudine-containing HAART. METHODS: We retrospectively analyzed
      the serial changes of plasma HBV DNA levels in 24 HBsAg-positive HIV-infected
      patients who entered the HAART program. A polymerase chain reaction-based assay,
      capable of quantifying as few as 400 HBV copies/ml, was used. The median follow
      up time was 18 months. RESULTS: HAART containing lamivudine 300 mg/day
      effectively suppressed plasma HBV-DNA to 10(-3)-10(-5)-fold of the baseline
      levels, but a multi-phasic decay of HBV DNA was observed. The later phases became
      flat, as a persistent residual HBV viremia, in eight of the studied 10 HBeAg
      positive patients; in contrast, residual HBV viremia was not observed in the 10
      HBeAg-negative patients studied (8/10 vs. 0/10, P=0.0007, Fisher's exact test).
      HAART without lamivudine did not suppress plasma HBV DNA levels in the remaining
      four patients. CONCLUSIONS: HAART containing lamivudine 300 mg/day effectively
      suppress HBV replication in HBeAg-negative HIV/HBV-coinfected patients.
      Nevertheless, residual HBV replication persisted in most HBeAg-positive
      coinfected patients.

PMID- 14642623
TI  - Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C
      virus infection. A multicenter Italian study.
AB  - BACKGROUND/AIMS: This study assess prevalence, risk factors, and clinical and
      virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV)
      infection. METHODS: We evaluated 837 hepatitis B surface antigen positive
      patients, prospectively enrolled in 14 Italian units. RESULTS: Anti-HCV was
      present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4%
      (>30-50) and 14% (>50). Independent predictors of dual infection were age >42
      years, history of I.V. drug use (IDU), blood transfusion and residence in the
      South of the country. The strength of the association with IDU was high, but this
      exposure accounted for five coinfection cases only. Cirrhosis was present in 107
      of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus
      coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol
      use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16
      (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both
      HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six
      (16.7%) tested negative for both. CONCLUSIONS: This study depicts the
      epidemiological and clinical burden of dual HBV/HCV infection in Italy.

PMID- 14642624
TI  - In overweight patients with chronic hepatitis C, circulating insulin is
      associated with hepatic fibrosis: implications for therapy.
AB  - BACKGROUND/AIMS: Host factors such as increased body mass index (BMI) and
      genotype-specific viral factors contribute to the development of steatosis in
      patients with chronic hepatitis C (HCV). We hypothesized that host metabolic
      factors associated with increased BMI may play a role in disease progression.
      METHODS: Fasting serum was collected from 160 patients with chronic HCV at the
      time of liver biopsy and 45 age, gender and BMI matched controls, and assessed
      for levels of insulin, c-peptide and leptin. RESULTS: Patients with viral
      genotype 3 had more severe steatosis (P=0.0001) and developed stages 1 and 2
      fibrosis at a younger age (P<0.05) than patients with genotype 1. For both
      genotypes, overweight patients had significantly more steatosis and increased
      insulin and leptin levels. In contrast to lean patients, there was a
      statistically significant increase in circulating insulin levels with increasing
      fibrosis in overweight patients with chronic HCV (P=0.03). Following multivariate
      analysis, insulin was independently associated with fibrosis (P=0.046) but not
      inflammation (P=0.83). There was no association between serum leptin levels and
      stage of fibrosis. CONCLUSIONS: Increasing circulating insulin levels may be a
      factor responsible for the association between BMI and fibrosis in patients with
      HCV, irrespective of viral genotype.

PMID- 14642625
TI  - Fibrogenic impact of high serum glucose in chronic hepatitis C.
AB  - BACKGROUND/AIMS: There is considerable variability in the rate of fibrosis
      progression in patients with chronic hepatitis C, most of which is related to
      factors so far unknown. We tested the hypothesis that high serum glucose and
      overweight might contribute to this variability. METHODS: Seven hundred and ten
      patients with chronic hepatitis C with a known duration of infection and no
      hepatitis B virus or human immunodeficiency virus coinfection were studied.
      Significant fibrosis was defined as bridging fibrosis including cirrhosis.
      Variables were tested for their association with significant fibrosis. RESULTS:
      In univariate analyses both serum glucose and body mass index were associated
      with fibrosis. In multivariate analyses, age at infection, duration of infection,
      serum glucose and daily alcohol intake but not body mass index were independently
      associated with significant fibrosis. Patients with high serum glucose had been
      contaminated at an older age and had features of the metabolic syndrome,
      including steatosis more frequently, as well as faster fibrosis progression
      rates. High serum glucose was associated with intermediate and advanced, but not
      with early, fibrosis stages. A high serum glucose was associated with a higher
      relative risk for significant fibrosis than overweight. CONCLUSIONS: High serum
      glucose, is an independent co-factor of fibrosis in chronic hepatitis C with a
      higher pro-fibrogenic impact than overweight.

PMID- 14642626
TI  - When and how to treat acute hepatitis C?
AB  - BACKGROUND: Appropriate treatment of acute hepatitis C is still a matter of
      controversy due to the lack of large controlled trials. AIM: To assess the
      effectiveness of interferon as treatment for acute hepatitis C by meta-analysis.
      METHODS: MEDLINE search (1985-2002) was supplemented with manual searches of
      reference lists. Studies were included if they were controlled trials comparing
      interferon to no treatment and if they included patients with either post
      transfusion or sporadic acute hepatitis C. Twelve trials were analyzed (414
      patients). The outcome assessed was the sustained virological response (SVR) rate
      (undetectable hepatitis C virus RNA in serum at least 6 months after cessation of
      therapy). RESULTS: Interferon significantly increased the SVR (risk difference
      49%; 95% confidence interval 32.9-65%) in comparison to no treatment. The risk
      difference of SVR increased from 5 to 90% when trials were ordered by increasing
      interferon weekly dose. Delaying therapy by 8-12 weeks after the onset of disease
      does not compromise the SVR rate. CONCLUSIONS: Current evidence is sufficient to
      recommend interferon treatment of patients with acute hepatitis C. A later
      initiation of therapy yields the same likelihood of response as early treatment.
      A daily induction dose during the 1st month is the best option of treatment.

PMID- 14642627
TI  - Core promoter/pre-core mutations are associated with lamivudine-induced HBeAg
      loss in chronic hepatitis B with genotype C.
AB  - BACKGROUND/AIMS: To clarify the factors associated with the efficacy of
      lamivudine. METHODS: Variables including basic core promoter (BCP) and pre-core
      (PreC) mutations were evaluated in 60 chronic hepatitis B e antigen (HBeAg)
      positive patients with genotype C. Thirty patients were treated with lamivudine
      and the remaining 30 patients were age- and sex-matched controls. RESULTS: Severe
      fibrosis was significantly more frequent in patients with the BCP-mutant/PreC
      wild (MW) and BCP-mutant/PreC-mutant (MM) patterns compared to BCP-wild/PreC-wild
      (WW) pattern (P=0.02). The cumulative rates of HBeAg loss at 6, 12 and 18 months
      were significantly higher in the lamivudine group (14.2, 36.3, and 60.9%)
      compared with the control group (17.6, 17.6, and 24.5%, P=0.03), and was
      especially pronounced in patients with the MW pattern (P=0.04). The rate of
      lamivudine-related HBeAg loss was significantly lower in patients with the WW
      pattern (P=0.03). Factors correlating with HBeAg loss were histological fibrosis
      and activity, hepatitis B virus-DNA levels, BCP/PreC mutation and lamivudine
      therapy. Multivariate analysis revealed BCP/PreC mutations and fibrosis were
      independent factors for HBeAg loss. CONCLUSIONS: With specific reference to the
      genotype C, we found earlier HBeAg loss was expected in patients carrying MM and
      MW patterns, while the efficacy of lamivudine was limited in patients with the WW
      pattern.

PMID- 14642628
TI  - Intrahepatic T cell survival versus death: which one prevails and why?

PMID- 14642629
TI  - Decreasing hepatic vascular tone by liver-specific NO donors: wishful thinking or
      a promising reality?

PMID- 14642630
TI  - Screening for hepatocellular carcinoma in cirrhosis.

PMID- 14642631
TI  - Selection of a hepatitis B virus strain resistant to adefovir in a liver
      transplantation patient.
AB  - BACKGROUND/AIMS: In contrast to lamivudine, adefovir dipivoxil (ADV) therapy is
      associated with delayed and infrequent selection of drug resistant hepatitis B
      virus (HBV). METHODS: A 52 year-old man was treated with lamivudine for an HBV
      recurrence on his liver graft. A viral breakthrough was observed and the patient
      received ADV. Serum HBV DNA decreased rapidly and lamivudine was discontinued
      while ADV monotherapy was maintained. Serum HBV DNA levels remained suppressed
      until a second breakthrough was observed. Lamivudine was then reintroduced
      together with ADV, and serum HBV DNA became undetectable by polymerase chain
      reaction. RESULTS: Sequence analyses of the HBV polymerase gene revealed a
      sequential selection of lamivudine resistance mutations L180M+M204V, followed by
      a reversion to wild-type, and subsequently the selection of a novel adefovir
      resistance mutation N236T. Phenotypic analyses in cell culture assays
      demonstrated that the HBV isolates at the time of ADV breakthrough had reduced
      susceptibility to ADV. This mutant remained sensitive to lamivudine, entecavir
      and emtricitabine in vitro. CONCLUSIONS: We describe the first case of sequential
      selection of lamivudine and adefovir resistant strains of HBV in a liver
      transplantation patient. The selection of the N236T polymerase mutant was
      associated with resistance to ADV but remained sensitive to lamivudine in vitro
      and in vivo.

PMID- 14642632
TI  - Images in Hepatology. Ciliated hepatic foregut cyst.

PMID- 14642633
TI  - Ductopenic hepatitis related to Enalapril.

PMID- 14642634
TI  - Severe toxic hepatitis related to chlormethiazole.

PMID- 14642635
TI  - Ursodeoxycholic acid and histological progression in primary biliary cirrhosis.

PMID- 14642636
TI  - Fatal liver failure with atorvastatin.

PMID- 14642639
TI  - Electrical stimulation of the dorsal periaqueductal gray decreases volume of the
      brain infarction independently of accompanying hypertension and
      cerebrovasodilation.
AB  - We investigated whether selective stimulation of neurons of the
      sympathoinhibitory ventral periaqueductal gray (VPAG), or sympathoexcitatory
      dorsal periaqueductal gray (DPAG), differentially modulates CBF and EEG and
      exerts neuroprotection. Electrical stimulation of either regions of PAG
      comparably elevated AP and CBF, whereas chemical stimulation with the D,L
      homocysteine produced either sympathoinhibition accompanied by decrease in CBF
      from ventral region or sympathoexcitation accompanied by increase in CBF from
      dorsal region in nonspinalized rats. The CBF effects evoked from DPAG and VPAG by
      chemical stimulation were preserved in spinalized rats supporting that the evoked
      CBF responses result directly from stimulation and are not secondary to AP
      changes. Stimulation of either region, whether chemical or electrical,
      synchronized the EEG. To explore whether PAG stimulation might protect the brain
      against ischemic injury, in other rats the VPAG or DPAG were stimulated for 1 h
      (50 Hz, 1 s on/1 s off, 75-100 microA) and the middle cerebral artery occluded 72
      h later. Stimulation of the DPAG, but not VPAG, significantly reduced infarction
      volumes relative to sham-stimulated controls as determined 24 h after occlusion.
      Elevations of AP and CBF did not differ between groups. We conclude: (a).
      intrinsic neurons of D- and VPAG differentially regulate CBF; (b). neurons of
      DPAG are neuroprotective independently of changes in CBF and/or AP. The DPAG
      effect on infarct volume may be related to the central neuroprotective pathway
      evoked by stimulation of the cerebellar FN.

PMID- 14642640
TI  - AMPA-induced dark cell degeneration of cerebellar Purkinje neurons involves
      activation of caspases and apparent mitochondrial dysfunction.
AB  - Cerebellar Purkinje neurons (PNs) are selectively vulnerable to AMPA (alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepriopionic acid)-induced delayed neurotoxicity
      known as dark cell degeneration (DCD) that is expressed as cytoplasmic and
      nuclear condensation, neuron shrinkage, and failure of physiology. The present
      study was initiated to determine whether AMPA-receptor-induced DCD in PNs is
      associated with Bax translocation to the mitochondria, cytochrome C release from
      the mitochondria, changes in mitochondrial potential, and activation of
      representative initiator and executor caspases that include caspase-9, caspase-3,
      and caspase-7. AMPA consistently and rapidly hyperpolarized mitochondria as
      reflected by an increase in MitoTracker Red CMS Ros fluorescence. Increases in
      Bax immunoreactivity were quantitatively and temporally variable and Bax failed
      to localize to mitochondria. Additionally, we observed a marked increase in
      immunoreactivity of cytochrome C although its release from mitochondria was not
      apparent. Mitochondrial membrane hyperpolarization and increases in cytochrome C
      immunoreactivity preceded caspase activation. Immunohistochemical analyses
      revealed the active form of caspases-3 and -9 were markedly and significantly
      increased in PNs following 30 microM AMPA, and caspase-9 activation preceded
      caspase-3. Increases in active caspase-7 immunoreactivity were less frequently
      encountered in PNs. Thus DCD shares some characteristics of apoptotic programmed
      cell death, but lacks typical mitochondrial pathophysiology associated with
      classic apoptosis. These findings suggest that AMPA-induced DCD is a form of
      active PCD that lies on a spectrum between classical apoptosis and passive
      necrosis.

PMID- 14642641
TI  - Interaction between discrete and rhythmic movements: reaction time and phase of
      discrete movement initiation during oscillatory movements.
AB  - This study investigates a task in which discrete and rhythmic movements are
      combined in a single-joint elbow rotation. Previous studies reported a tendency
      for the EMG burst associated with the discrete movement to occur around the
      expected burst associated with the rhythmic movement (e.g., [Exp. Brain Res. 99
      (1994) 325; J. Neurol. Neurosurg. Psychiatry 40 (1977) 1129; Hum. Mov. Sci. 19
      (2000) 627]). We document this interaction between discrete and rhythmic
      movements in different task variations and suggest a model consisting of rhythmic
      and discrete pattern generators that reproduces the major results. In the
      experiment, subjects performed single-joint elbow oscillatory movements (2 Hz).
      Upon a signal, they initiated a movement that consisted of a shift in the
      midpoint of the oscillation (MID), a shift in the amplitude of the oscillation
      (AMP), or a combination of both (MID + AMP). These shifting movements were
      performed either in a reaction time or in a self-paced fashion. The tendency for
      the EMG bursts associated with the discrete and rhythmic movements to synchronize
      was found similarly in all three tasks and instruction conditions, but the
      synchronization was most pronounced in the self-initiated discrete movement.
      Reaction time was increased for the combined task (MID + AMP), indicating higher
      control demands due to a combination of discrete and rhythmic components. This
      EMG burst synchronization was reproduced in a model based on a half-center
      oscillator with activation signals that produce either rhythmic or discrete
      activity. This activity was interpreted as torques driving a simple limb model.
      Summation of discrete and rhythmic activation signals of the pattern generators
      was sufficient to simulate the EMG burst synchronization. Further, simulation
      data reproduced the modulation of the reaction time as a function of the phase of
      the discrete movement.

PMID- 14642642
TI  - Calcium current in type I hair cells isolated from the semicircular canal crista
      ampullaris of the rat.
AB  - The low voltage gain in type I hair cells implies that neurotransmitter release
      at their afferent synapse should be mediated by low voltage activated calcium
      channels, or that some peculiar mechanism should be operating in this synapse.
      With the patch clamp technique, we studied the characteristics of the Ca(2+)
      current in type I hair cells enzymatically dissociated from rat semicircular
      canal crista ampullaris. Calcium current in type I hair cells exhibited a slow
      inactivation (during 2-s depolarizing steps), was sensitive to nimodipine and was
      blocked by Cd(2+) and Ni(2+). This current was activated at potentials above -60
      mV, had a mean half maximal activation of -36 mV, and exhibited no steady-state
      inactivation at holding potentials between -100 and -60 mV. This data led us to
      conclude that hair cell Ca(2+) current is most likely of the L type. Thus, other
      mechanisms participating in neurotransmitter release such as K(+) accumulation in
      the synaptic cleft, modulation of K(+) currents by nitric oxide, participation of
      a Na(+) current and possible metabotropic cascades activated by depolarization
      should be considered.

PMID- 14642643
TI  - Increased brain uptake and CSF clearance of 14C-glutamate in spontaneously
      hypertensive rats.
AB  - Blood-to-brain and blood-to-CSF transport kinetics of 14C-glutamate in the
      spontaneously hypertensive rats (SHR) were studied using the in situ brain
      perfusion technique. Also, clearance of 14C-glutamate from CSF of SHR was studied
      using the ventriculo-cisternal (VC) perfusion technique. Blood-to-brain and blood
      to-CSF transport kinetics showed greater rate of maximal transport into both
      brain and CSF of SHR compared to normotensive Wistar Kyoto (WKY) rats (p>0.05).
      Uptake into CSF of WKY and uptakes into brains of WKY and SHR did not show any
      significant diffusion (K(d)) of 14C-glutamate (p<0.05). However, some diffusion
      of 14C-glutamate only into CSF of SHR was observed, 0.031+0.006 microl min(-1) g(
      1). Clearance of 14C-glutamate from CSF was greater in the SHR (28.33+/-6.9
      microl min(-1)) compared to that in WKY rats (19.42+/-4.7 microl min(-1)).
      However, 14C-glutamate uptake by brain from CSF side was not significantly
      different between SHR and WKY rats (p>0.05). These results suggest that the
      greater blood-to-brain and blood-to-CSF entry of 14C-glutamate during
      hypertension may be balanced by greater removal of 14C-glutamate from CSF back to
      blood.

PMID- 14642644
TI  - Memantine attenuates the increase in striatal preproenkephalin mRNA expression
      and development of haloperidol-induced persistent oral dyskinesias in rats.
AB  - Tardive dyskinesia (TD) is a serious motor side effect of long-term neuroleptic
      treatment that may persist after drug withdrawal. Alterations in striatal
      enkephalinergic neurons due to excessive glutamatergic activity is a possible
      pathogenetic mechanism. We studied the effect of the NMDA antagonist memantine in
      a rat model of TD, in which vacuous chewing movements (VCM) were induced by 20
      weeks of haloperidol administration. The striatal density of preproenkephalin
      mRNA was measured and the number of neurons estimated. Haloperidol induced
      persistent VCM that was associated with increased striatal expression of
      preproenkephalin mRNA. Memantine inhibited the development of haloperidol-induced
      persistent VCM and attenuated the increase in preproenkephalin mRNA expression.
      This suggests that glutamate-mediated up-regulation of striatal enkephalin plays
      a role in the development of haloperidol-induced persistent oral dyskinesias.

PMID- 14642645
TI  - Purkinje cell activity during learning a new timing in classical eyeblink
      conditioning.
AB  - During classical eyeblink conditioning, animals acquire adaptive timing of the
      conditioned response (CR) to the interstimulus interval (ISI) between the
      conditioned stimulus (CS) and the unconditioned stimulus (US). To investigate
      this coding of the timing by the cerebellum, we analyzed Purkinje cell activities
      during acquisition of new timing after we shifted the ISI. Decerebrate guinea
      pigs were conditioned to an asymptotic level of learning using a delay paradigm
      with a 250-ms ISI. A 350-ms tone and a 100-ms electrical shock were used as the
      CS and US, respectively. As reported previously in other species, Purkinje cells
      in the simplex lobe exhibited three types of responses to the CS: excitatory,
      inhibitory, or a combination of the two. After we increased the ISI to 400 ms,
      the frequency of the CR stayed at an asymptotic level, but the latency of the CR
      peak became gradually longer. Two types of cells were observed, based on changes
      in the nature of their response to the CS; one changed its type of response in
      parallel with learning the new timing, while the other did not. There was no
      correlation between the type of response before and after we changed the ISI. In
      some cells, the peak latency of activities became longer or shorter, while the
      type of response did not change. These results suggest that some Purkinje cells
      code the timing of the CR, but do not play a consistent role in shaping the CR
      over a range of ISIs.

PMID- 14642646
TI  - Acute effects of 3,4-methylenedioxymethamphetamine on striatal single-unit
      activity and behavior in freely moving rats: differential involvement of dopamine
      D(1) and D(2) receptors.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused amphetamine
      derivative that increases dopamine (DA) and serotonin release via a reverse
      transport mechanism. Changes in the activity of striatal neurons in response to
      increased DA transmission may shape the behavioral patterns associated with
      amphetamine-like stimulants. To determine how the striatum participates in MDMA
      induced locomotor activation, we recorded the activity of >100 single units in
      the striatum of freely moving rats in response to a dose that increased motor
      activation (5.0 mg/kg). MDMA had a predominantly excitatory effect on neuronal
      activity that was positively correlated with the magnitude of locomotor
      activation. Categorizing neurons according to baseline locomotor responsiveness
      revealed that MDMA excited significantly more neurons showing movement-related
      increases in activity compared to units that were non-movement-related or
      associated with movement-related decreases in activity. Further analysis revealed
      that the drug-induced striatal activation was not simply secondary to the
      behavioral change, indicating a primary action of MDMA on striatal motor
      circuits. Prior administration of SCH-23390 (0.2 mg/kg), a D(1) antagonist,
      resulted in a late onset of MDMA-induced locomotion, which correlated positively
      with delayed neuronal excitations. Conversely, prior administration of
      eticlopride (0.2 mg/kg), a D(2) antagonist, completely abolished MDMA-induced
      locomotion, which paralleled its blockade of MDMA-induced excitatory neuronal
      responses. Our results highlight the importance of striatal neuronal activity in
      shaping the behavioral response to MDMA, and suggest that DA D(1) and D(2)
      receptors have distinct functional roles in the expression of MDMA-induced
      striatal and locomotor activation.

PMID- 14642647
TI  - Characterization of the chick carrageenan response.
AB  - The present study characterized carrageenan inflammatory nociception in the 7-day
      old domestic chick. The time course effects of foot withdrawal latency to a
      thermal stimulus and edema were examined over a 6-h period following an
      intraplantar carrageenan (0.0-1.0%) injection. Carrageenan-induced hyperalgesia
      and edema had a similar course of action, enduring for approximately 6 h, with a
      peak effect at approximately 2 h post carrageenan injection. Carrageenan
      inflammation was produced in a robust concentration dependent manner. Carrageenan
      hyperalgesia was induced at all concentrations tested and no carrageenan
      concentration effects were discerned. In a subsequent series of experiments we
      challenged the carrageenan inflammation model with systemic administration of the
      opioid agonist morphine, the nonsteroidal anti-inflammatory drug naproxen or the
      steroidal antiinflammatory drug dexamethasone. Morphine produced a dose dependent
      attenuation of carrageenan hyperalgesia but had no effect upon carrageenan
      inflammation. Naproxen produced a moderate attenuation of carrageenan
      inflammation and hyperalgesia. Dexamethasone dramatically attenuated both
      carrageenan hyperalgesia and inflammation. Collectively, these experiments
      characterize the chick carrageenan response and demonstrate the potential of the
      chick carrageenan inflammation model as a less expensive adjunct model of
      inflammatory nociception.

PMID- 14642648
TI  - Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine
      during early memory consolidation in the day-old chick.
AB  - Passive avoidance learning is with advantage studied in day-old chicks trained to
      distinguish between beads of two different colors, of which one at training was
      associated with aversive taste. During the first 30-min post-training, two
      periods of glutamate release occur in the forebrain. One period is immediately
      after the aversive experience, when glutamate release is confined to the left
      hemisphere. A second release, 30 min later, may be bilateral, perhaps with
      preponderance of the right hemisphere. The present study showed increased pool
      sizes of glutamate and glutamine, specifically in the left hemisphere, at the
      time when the first glutamate release occurs, indicating de novo synthesis of
      glutamate/glutamine from glucose or glycogen, which are the only possible
      substrates. Behavioral evidence that memory is extinguished by intracranial
      administration at this time of iodoacetate, an inhibitor of glycolysis and
      glycogenolysis, and that the extinction of memory is counteracted by injection of
      glutamine, supports this concept. A decrease in forebrain glycogen of similar
      magnitude and coinciding with the increase in glutamate and glutamine suggests
      that glycogen rather than glucose is the main source of newly synthesized
      glutamate/glutamine. The second activation of glutamatergic activity 30 min after
      training, when memory is consolidated into stable, long-term memory, is
      associated with a bilateral increase in pool size of glutamate/glutamine. No
      glycogenolysis was observed at this time, but again there is a temporal
      correlation with sensitivity to inhibition by iodoacetate and rescue by
      glutamine, indicating the importance of de novo synthesis of glutamate/glutamine
      from glucose or glycogen.

PMID- 14642649
TI  - Effects of subtypes of adrenergic and angiotensinergic antagonists on the water
      and sodium intake induced by adrenaline injected into the paraventricular
      nucleus.
AB  - The present experiments were conducted to investigate the role of the alpha(1A)-,
      alpha(1B)-, beta(1)-, beta(2)-adrenoceptors, and the effects of losartan and
      CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors,
      respectively) on the water and sodium intake elicited by paraventricular nucleus
      (PVN) injection of adrenaline. Male Holtzman rats with a stainless steel cannula
      implanted into the PVN were used. The ingestion of water and sodium was
      determined in separate groups submitted to water deprivation or sodium depletion
      with the diuretic furosemide (20 mg/rat). 5-Methylurapidil (an alpha(1A)
      adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected
      into the PVN produced a dose-dependent increase, whereas cyclazosin (an alpha(1B)
      adrenergic antagonist) and atenolol (a beta(1)-adrenergic antagonist) do not
      affect the inhibitory effect of water intake induced by adrenaline. On the other
      hand, the PVN administration of adrenaline increased the sodium intake in a dose
      dependent manner. Previous injection of the alpha(1A) and beta(1) antagonists
      decreased, whereas injection of the alpha(1B) and beta(2) antagonists increased
      the salt intake induced by adrenaline. In rats with several doses of adrenaline
      into PVN, the previous administration of losartan increased in a dose-dependent
      manner the inhibitory effect of adrenaline and decreased the salt intake induced
      by adrenaline, while PVN CGP42112A was without effect. These results indicate
      that both appetites are mediated primarily by brain AT(1) receptors. However, the
      doses of losartan were more effective when combined with the doses of CGP42112A
      than given alone p<0.05, suggesting that the water and salt intake effects of PVN
      adrenaline may involve activation of multiple angiotensin II (ANG II) receptors
      subtypes.

PMID- 14642650
TI  - Injury and strain-dependent dopaminergic neuronal degeneration in the substantia
      nigra of mice after axotomy or MPTP.
AB  - We studied the effects of axotomy or neurotoxin on the survival of substantia
      nigra pars compacta (SNpc) neurons in two strains of mice, FVB/N or C57BL/6.
      Fluoro gold (FG) was injected into both striata of the mice to retrogradely label
      the nigrostriatal neuronal population. Ten days later, these neurons were
      axotomized in the medial forebrain bundle (MFB) unilaterally or N-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) was administered intraperitonealy for 2 days to
      produce bilateral degeneration. MFB transection or MPTP administration produced a
      progressive loss of FG-labeled and tyrosine hydroxylase immunolabeled (TH+)
      neurons in both strains. Relative to control, 72% of SNpc neurons died 4 weeks
      after axotomy in C57BL/6 mice and 50% died after axotomy in FVB/N mice. MPTP
      resulted in death of 80% of SNpc neurons in C57BL/6 mice but only 40% in the FVB
      strain 4 weeks after MPTP administration. In this more sensitive strain, MPTP
      cell death was associated with positive staining for terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) and nuclear condensation. In
      contrast, no TUNEL staining was detected in SNpc after MPTP in FVB/N mice.
      Further, while similar kinetics and extent of cell death accompanied axotomy,
      axotomy-induced cell death was TUNEL negative in both FVB/N and C57BL/6 mice.
      Double staining for TUNEL and microtubule associated protein 2 confirmed that the
      majority of the TUNEL positive cells were neurons. These data indicate that
      genetic factors and the type of lesion play an important role in determining
      death of dopaminergic neurons after injury.

PMID- 14642651
TI  - Immunohistochemical study on the distribution of insulin-like growth factor I
      (IGF-I) receptor in the central nervous system of SOD1(G93A) mutant transgenic
      mice.
AB  - In the present study, we used the SOD1(G93A) mutant transgenic mice as an in vivo
      model of ALS and performed immunohistochemical studies to investigate the changes
      of insulin-like growth factor I (IGF-I) receptor in the central nervous system.
      IGF-I receptor-immunoreactive astrocytes were detected in the spinal cord,
      brainstem, central gray and cerebellar nuclei of SOD1(G93A) transgenic mice. In
      contrast to transgenic mice, no IGF-I receptor-immunoreactive astrocytes were
      observed in any brain region of wtSOD1 transgenic mice although a few moderately
      stained neurons were observed. In the hippocampal formation of SOD1(G93A)
      transgenic mice, IGF-I receptor immunoreactivity was increased in the pyramidal
      cells of the CA1-3 regions and granule cells of the dentate gyrus. The present
      study provides the first evidence that IGF-I receptor immunoreactivity was
      increased in reactive astrocytes in the central nervous system of SOD(G93A)
      transgenic mice, suggesting that reactive astrocytes may play an important role
      in the pathogenesis and progress of ALS. The mechanisms underlying the increased
      immunoreactivity for IGF-I receptor, and the functional implications of these
      increases, require elucidation.

PMID- 14642652
TI  - Specific localization of signal transducer and activator of transcription 1
      immunoreactivity in oxytocin neurons of the rat hypothalamus.
AB  - The transcription factor STAT1 participates in signaling pathways and cellular
      responses triggered by several cytokines, growth factors and hormones. The
      present work demonstrates for the first time the immunohistochemical distribution
      of STAT1 in the rat hypothalamus. STAT1 immunoreactivity was observed in somas,
      dendrites and axons of neurons throughout the supraoptic and paraventricular
      nuclei and co-localized specifically with oxytocin. These findings indicate that
      STAT1 is positioned to participate in specific neuroendocrine regulation in the
      nonpathological rat brain.

PMID- 14642653
TI  - GABA(A) receptor subunit and gephyrin protein changes differ in the globus
      pallidus in Huntington's diseased brain.
AB  - Immunoreactivity of GABA(A) receptor subunits and the receptor anchoring protein
      gephyrin was investigated in the human globus pallidus using antibodies raised
      against the alpha(1) and gamma(2) subunits of the GABA(A) receptor complex and
      gephyrin. The results revealed increased GABA(A) receptor subunit
      immunoreactivity and unchanged levels of gephyrin immunoreactivity in
      Huntington's diseased (HD) globus pallidus (GP). The results demonstrate that
      gephyrin immunoreactivity did not change in unison with GABA(A) receptor changes
      in HD, suggesting that the receptor anchoring protein gephyrin is unaltered and
      maintains a stable lattice structure in the face of GABA(A) receptor changes in
      HD.

PMID- 14642655
TI  - Improved Hidden Markov Model training for multiple sequence alignment by a
      particle swarm optimization-evolutionary algorithm hybrid.
AB  - Multiple sequence alignment (MSA) is one of the basic problems in computational
      biology. Realistic problem instances of MSA are computationally intractable for
      exact algorithms. One way to tackle MSA is to use Hidden Markov Models (HMMs),
      which are known to be very powerful in the related problem domain of speech
      recognition. However, the training of HMMs is computationally hard and there is
      no known exact method that can guarantee optimal training within reasonable
      computing time. Perhaps the most powerful training method is the Baum-Welch
      algorithm, which is fast, but bears the problem of stagnation at local optima. In
      the study reported in this paper, we used a hybrid algorithm combining particle
      swarm optimization with evolutionary algorithms to train HMMs for the alignment
      of protein sequences. Our experiments show that our approach yields better
      alignments for a set of benchmark protein sequences than the most commonly
      applied HMM training methods, such as Baum-Welch and Simulated Annealing.

PMID- 14642656
TI  - Evolutionary computation method for pattern recognition of cis-acting sites.
AB  - This paper develops an evolutionary method that learns inductively to recognize
      the makeup and the position of very short consensus sequences, cis-acting sites,
      which are a typical feature of promoters in genomes. The method combines a Finite
      State Automata (FSA) and Genetic Programming (GP) to discover candidate promoter
      sequences in primary sequence data. An experiment measures the success of the
      method for promoter prediction in the human genome. This class of method can take
      large base pair jumps and this may enable it to process very long genomic
      sequences to discover gene specific cis-acting sites, and genes which are
      regulated together.

PMID- 14642657
TI  - A permutation-based genetic algorithm for the RNA folding problem: a critical
      look at selection strategies, crossover operators, and representation issues.
AB  - This paper presents a Genetic Algorithm (GA) to predict the secondary structure
      of RNA molecules, where the secondary structure is encoded as a permutation. More
      specifically, the proposed algorithm predicts which specific canonical base pairs
      will form hydrogen bonds and build helices, also known as stems. Since RNA is
      involved in both transcription and translation and also has catalytic and
      structural roles in the cell, determining the structure of RNA is of fundamental
      importance in helping to determine RNA function. We introduce a GA where a
      permutation is used to encode the secondary structure of RNA molecules. We
      discuss results on RNA sequences of lengths 76, 210, 681, and 785 nucleotides and
      present several improvements to our algorithm. We show that the Keep-Best
      Reproduction operator has similar benefits as in the traveling salesman problem
      domain. In addition, a comparison of several crossover operators is provided. We
      also compare the results of the permutation-based GA with a binary GA,
      demonstrating the benefits of the newly proposed representation.

PMID- 14642658
TI  - Inference of Euler angles for single-particle analysis by means of evolutionary
      algorithms.
AB  - Single-particle analysis is one of the methods for structural studies of protein
      and macromolecules; it requires advanced image analysis of electron
      micrographics. Reconstructing three-dimensional (3D) structure from microscope
      images is not an easy analysis because of the low image resolution of images and
      lack of the directional information of images in 3D structure. To improve the
      resolution, different projections are aligned, classified, and averaged.
      Inferring the orientations of these images is so difficult that the task of
      reconstructing 3D structures depends upon the experience of researchers. But
      recently, a method to reconstruct 3D structures was automatically devised. In
      this paper, we propose a new method for determining Euler angles of projections
      by applying genetic algorithms. We empirically show that the proposed approach
      has improved the previous one in terms of computational time and acquired
      precision.

PMID- 14642659
TI  - Flexible ligand docking using evolutionary algorithms: investigating the effects
      of variation operators and local search hybrids.
AB  - The docking of ligands to proteins can be formulated as a computational problem
      where the task is to find the most favorable energetic conformation among the
      large space of possible protein-ligand complexes. Stochastic search methods such
      as evolutionary algorithms (EAs) can be used to sample large search spaces
      effectively and is one of the commonly used methods for flexible ligand docking.
      During the last decade, several EAs using different variation operators have been
      introduced, such as the ones provided with the AutoDock program. In this paper we
      evaluate the performance of different EA settings such as choice of variation
      operators, population size, and usage of local search. The comparison is
      performed on a suite of six docking problems previously used to evaluate the
      performance of search algorithms provided with the AutoDock program package. The
      results from our investigation confirm that the choice of variation operators has
      an impact on the search-capabilities of EAs. The introduced DockEA using the best
      settings found obtained the overall best docking solutions compared to the
      Lamarckian GA (LGA) provided with AutoDock. Furthermore, the DockEA proved to be
      more robust than the LGA (in terms of reproducing the results in several runs) on
      the more difficult problems with a high number of flexible torsion angles.

PMID- 14642660
TI  - A memetic-aided approach to hierarchical clustering from distance matrices:
      application to gene expression clustering and phylogeny.
AB  - We propose a heuristic approach to hierarchical clustering from distance matrices
      based on the use of memetic algorithms (MAs). By using MAs to solve some variants
      of the Minimum Weight Hamiltonian Path Problem on the input matrix, a sequence of
      the individual elements to be clustered (referred to as patterns) is first
      obtained. While this problem is also NP-hard, a probably optimal sequence is easy
      to find with the current advances for this problem and helps to prune the space
      of possible solutions and/or to guide the search performed by an actual
      clustering algorithm. This technique has been successfully applied to both a
      Branch-and-Bound algorithm, and to evolutionary algorithms and MAs. Experimental
      results are given in the context of phylogenetic inference and in the
      hierarchical clustering of gene expression data.

PMID- 14642661
TI  - Analysis of gene expression profiles: an application of memetic algorithms to the
      minimum sum-of-squares clustering problem.
AB  - Microarrays have become a key technology in experimental molecular biology since
      they allow monitoring of gene expression for more than 10,000 genes in parallel
      producing huge amounts of data. In the exploration of transcriptional regulatory
      networks, an important task is to cluster gene expression data to identify groups
      of genes with similar patterns and hence similar function. In this paper, memetic
      algorithms (MAs)-evolutionary algorithms incorporating local search-are proposed
      for minimum sum-of-squares clustering (MSSC). In a fitness landscape analysis, it
      is shown that the MSSC problem has correlation structure exploitable by MAs. The
      proposed MAs are shown to be superior to multi-start k-means as well as five
      other clustering algorithms from the bioinformatics literature including
      hierarchical algorithms and self-organizing maps. Although the fitness values of
      the different clustering solutions lie close together, it is shown that the
      solutions differ significantly from each other in terms of cluster memberships
      which is extremely important for the biological interpretation of the clustering
      results.

PMID- 14642662
TI  - Reliable classification of two-class cancer data using evolutionary algorithms.
AB  - In the area of bioinformatics, the identification of gene subsets responsible for
      classifying available disease samples to two or more of its variants is an
      important task. Such problems have been solved in the past by means of
      unsupervised learning methods (hierarchical clustering, self-organizing maps, k
      mean clustering, etc.) and supervised learning methods (weighted voting approach,
      k-nearest neighbor method, support vector machine method, etc.). Such problems
      can also be posed as optimization problems of minimizing gene subset size to
      achieve reliable and accurate classification. The main difficulties in solving
      the resulting optimization problem are the availability of only a few samples
      compared to the number of genes in the samples and the exorbitantly large search
      space of solutions. Although there exist a few applications of evolutionary
      algorithms (EAs) for this task, here we treat the problem as a multiobjective
      optimization problem of minimizing the gene subset size and minimizing the number
      of misclassified samples. Moreover, for a more reliable classification, we
      consider multiple training sets in evaluating a classifier. Contrary to the past
      studies, the use of a multiobjective EA (NSGA-II) has enabled us to discover a
      smaller gene subset size (such as four or five) to correctly classify 100% or
      near 100% samples for three cancer samples (Leukemia, Lymphoma, and Colon). We
      have also extended the NSGA-II to obtain multiple non-dominated solutions
      discovering as much as 352 different three-gene combinations providing a 100%
      correct classification to the Leukemia data. In order to have further confidence
      in the identification task, we have also introduced a prediction strength
      threshold for determining a sample's belonging to one class or the other. All
      simulation results show consistent gene subset identifications on three disease
      samples and exhibit the flexibilities and efficacies in using a multiobjective EA
      for the gene subset identification task.

PMID- 14642663
TI  - Artificial neural networks for species identification by taxonomists.
AB  - This paper is a study of the value of applying artificial neural networks (ANNs),
      specifically a multilayer perceptron (MLP), to identification of higher plants
      using morphological characters collected by conventional means. A practical
      methodology is thus demonstrated to enable botanical or zoological taxonomists to
      use ANNs as advisory tools for identification purposes. A comparison is made
      between the ability of the neural network and that of traditional methods for
      plant identification by means of a case study in the flowering plant genus
      Lithops N.E. Brown (Aizoaceae). In particular, a comparison is made with
      taxonomic keys generated by means of the DELTA system. The ANN is found to
      perform better than the DELTA key generator, for conditions where the available
      data is limited, and species relatively difficult to distinguish.

PMID- 14642664
TI  - Evolutionary optimization, backpropagation, and data preparation issues in QSAR
      modeling of HIV inhibition by HEPT derivatives.
AB  - Artificial neural networks (ANNs) can be utilized to generate predictive models
      of quantitative structure-activity relationships between a set of molecular
      descriptors and activity. Evolutionary computation provides a means to
      appropriately search for the set of weights and bias terms associated with
      artificial neural networks that minimize selected functions of the error between
      the actual and desired outputs. This method is demonstrated by evolutionary
      training of artificial neural networks capable of predicting anti-HIV activity
      for a set of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
      derivatives. The results of this work further confirm the growing indication that
      evolutionary computation can outperform backpropagation as a method of artificial
      neural network training. The results also indicate the degree to which bias in
      the initial training and testing data can affect performance and the importance
      of bootstrapping.

PMID- 14642665
TI  - Searching for discrimination rules in protease proteolytic cleavage activity
      using genetic programming with a min-max scoring function.
AB  - This paper presents an algorithm which is able to extract discriminant rules from
      oligopeptides for protease proteolytic cleavage activity prediction. The
      algorithm is developed using genetic programming. Three important components in
      the algorithm are a min-max scoring function, the reverse Polish notation (RPN)
      and the use of minimum description length. The min-max scoring function is
      developed using amino acid similarity matrices for measuring the similarity
      between an oligopeptide and a rule, which is a complex algebraic equation of
      amino acids rather than a simple pattern sequence. The Fisher ratio is then
      calculated on the scoring values using the class label associated with the
      oligopeptides. The discriminant ability of each rule can therefore be evaluated.
      The use of RPN makes the evolutionary operations simpler and therefore reduces
      the computational cost. To prevent overfitting, the concept of minimum
      description length is used to penalize over-complicated rules. A fitness function
      is therefore composed of the Fisher ratio and the use of minimum description
      length for an efficient evolutionary process. In the application to four protease
      datasets (Trypsin, Factor Xa, Hepatitis C Virus and HIV protease cleavage site
      prediction), our algorithm is superior to C5, a conventional method for deriving
      decision trees.

PMID- 14642667
TI  - Model selection methodology in supervised learning with evolutionary computation.
AB  - The expressive power, powerful search capability, and the explicit nature of the
      resulting models make evolutionary methods very attractive for supervised
      learning applications in bioinformatics. However, their characteristics also make
      them highly susceptible to overtraining or to discovering chance relationships in
      the data. Identification of appropriate criteria for terminating evolution and
      for selecting an appropriately validated model is vital. Some approaches that are
      commonly applied to other modelling methods are not necessarily applicable in a
      straightforward manner to evolutionary methods. An approach to model selection is
      presented that is not unduly computationally intensive. To illustrate the issues
      and the technique two bioinformatic datasets are used, one relating to metabolite
      determination and the other to disease prediction from gene expression data.

PMID- 14642666
TI  - Petri net modeling of high-order genetic systems using grammatical evolution.
AB  - Understanding how DNA sequence variations impact human health through a hierarchy
      of biochemical and physiological systems is expected to improve the diagnosis,
      prevention, and treatment of common, complex human diseases. We have previously
      developed a hierarchical dynamic systems approach based on Petri nets for
      generating biochemical network models that are consistent with genetic models of
      disease susceptibility. This modeling approach uses an evolutionary computation
      approach called grammatical evolution as a search strategy for optimal Petri net
      models. We have previously demonstrated that this approach routinely identifies
      biochemical network models that are consistent with a variety of genetic models
      in which disease susceptibility is determined by nonlinear interactions between
      two DNA sequence variations. In the present study, we evaluate whether the Petri
      net approach is capable of identifying biochemical networks that are consistent
      with disease susceptibility due to higher order nonlinear interactions between
      three DNA sequence variations. The results indicate that our model-building
      approach is capable of routinely identifying good, but not perfect, Petri net
      models. Ideas for improving the algorithm for this high-dimensional problem are
      presented.

PMID- 14642668
TI  - [Analgesic physical therapy. Present clinical data].
AB  - Analgesic electrotherapy is now based on more consistent scientific data; the
      biological action of the electric current, of the electromagnetic radiations and
      of the mechanical vibrations is better approached. But the randomized control
      trials still provide contradictory results concerning the analgesic efficiency of
      the cryotherapy, the TENS, the pulsed electro-magnetic fields, the ultrasound and
      laser therapy, the shock waves; iontophoresis, short waves, microwaves,
      infrasound vibrations are very few investigated. The analgesic electrotherapy
      cannot be recommended nor prohibited; physical agents represent only therapeutic
      options. On the basis of the scientific data and of their personal experience,
      the therapists can use them. More controlled clinical investigations of higher
      methodological levels are still required.

PMID- 14642669
TI  - [Aging with spinal cord injury].
AB  - OBJECTIVE: Literature review of the data on aging with spinal cord injury.
      METHOD: Interrogation on Medline using the following keywords: aging, spinal cord
      injuries, paraplegia, quadriplegia, mortality, morbidity, quality of life,
      survival, health status. RESULTS: The expectation of life of the spinal cord
      injury patients improved even though it remains even lower than that of the
      general population. The effects of aging add to the specific complications which
      are numerous and alter almost every function. Respiratory complications became
      the first cause of death especially for tetraplegics. Urinary and cutaneous
      complications remain important as well as osteo-articular pathologies (particular
      upper limbs) whose consequences can be serious on the functional capacities.
      Studies on the quality of life show that adaptation to the handicap is done in a
      continuous way and a long time after the initial phase of rehabilitation. They
      underline the importance of professional resources, psychological reactions and
      previous experiences of the spinal cord injury patients in appreciating the
      quality of life after the traumatism. CONCLUSION: The specificities of the aging
      of the spinal cord injury patients require to be well known and underline the
      importance and the necessity of an adequate and specific follow-up. On a more
      general plan, they imply a reflection on the strategies of initial
      rehabilitation, not to compromise the future of these spinal cord injury
      patients.

PMID- 14642670
TI  - [Aging of injured spinal cord].

PMID- 14642671
TI  - [Detrusor activity and motor neurons firing during micturition: analysis by means
      of modeling of urodynamic tracings].
AB  - BACKGROUND: To use a computer assisted analysis of urodynamic tracings (VBN
      method) in order to propose a quantitative description of the relationship
      between detrusor activity and firing of efferent motor neurons. METHODS: Modeling
      of the nervous control implies three definitions of the detrusor excitation: (1)
      related to the contractile force (EF), (2) related to the calcium turnover (ECa)
      and (3) ratio of firing motor neurons (rr). The associate variables have been
      computed from each uroflow recording of healthy volunteers (male and female) and
      patients (107 men with lower urinary tract symptoms due to benign prostatic
      enlargement and 138 women with stress urinary incontinence). RESULTS: A "standard
      excitation" governs all the voidings of healthy volunteers. For 47% of male
      patients and 75% of female patients, a non-standard excitation is observed:
      beginning as the standard excitation, then sudden break at a time tc (9.7 +/- 2.5
      s for male and 4.0 +/- 2.7 s for women). rr has an all-or-none value in case of
      standard excitation and exhibits a two steps behavior with after tc: = 0.53 +/-
      0.21 for men and 0.41 +/- 0.18 for women (non-significant despite the difference
      in the origin of disease). CONCLUSION: VBN computer analysis of urodynamic
      tracings allows to propose a description of the detrusor nervous control: (1) an
      on-off nervous order rules the "standard" detrusor activity, and (2) a feedback,
      which probably starts at the urethral level, acts to switch an on-off reduction
      of the detrusor activity in the other cases.

PMID- 14642672
TI  - [Consequences and prediction of hamstring muscle injury with concentric and
      eccentric isokinetic parameters in elite soccer players].
AB  - OBJECTIVE: To know if isokinetic parameters identify previous hamstring (H)
      injury and predict a new muscle injury in high-level soccer player. METHOD:
      Concentric (con) and eccentric (ecc) isokinetic torque was measured at the
      angular speed of 60 degrees /s in 28 elite soccer players (23 years +/- 3.3; 74
      kg +/- 7.5; 178 cm +/- 6.5). First, 11 players, victims of 15 moderate or major
      hamstring injuries in the preceding 2 years, were compared with 17 players
      without previous hamstring injury. Comparisons were carried out from isokinetic
      knee flexors-extensors ratios [Hcon/Qcon and Hecc/Qcon] and bilateral knee
      flexors ratios [Hcon/Hcon and Hecc/Hecc]. Secondly, all the population was
      followed during 12 months and the isokinetic muscular profile of players who
      presented a recurrence or a new hamstring muscle injury was analysed. RESULTS: A
      concentric ratio hamstring-to-quadriceps lower than 0.6 and a hamstring asymmetry
      of more than 10% do not allow to identify previous hamstring injury. On the other
      hand, the mixed ratio eccentric hamstring-to-concentric quadriceps lower than 0.6
      represents the best indicator (probability: 77.5%). The rate of recurrence is 30%
      (three cases of 10) and the rate of new hamstring muscle injury is 31% (five
      cases of 16) (P > 0.05). One of the five injured soccer players presented a
      concentric ratio hamstring-to-quadriceps lower than 0.6 and no player presented a
      mixed ratio lower than 0.6. However, four of the five injured players presented a
      concentric and an eccentric asymmetry. But, it is the strongest side, which
      presented a new hamstring muscle injury. CONCLUSION: The mixed ratio eccentric
      hamstring-to-concentric quadriceps lower than 0.6 identify a previous hamstring
      injury despite the resumption of competitive soccer. However, this ratio and the
      others isokinetic studied parameters do not predict a recurrence or a new
      hamstring muscle injury.

PMID- 14642673
TI  - [Benefit of rotational exercises for patients with Meniere's syndrome, method
      used by the ENT department of St-Luc university clinic].
AB  - OBJECTIVE: To date, the effectiveness of balanced rehabilitation for patients
      with Meniere's syndrome has not been unanimously acknowledged by all physicians
      and physiotherapists. The purpose of this study is to assess the therapeutic
      efficacy of rotational exercises in the treatment of disequilibrium for patients
      with unilateral Meniere's syndrome. METHODOLOGY: Rotational stimuli were used to
      symmetrize and reduce postrotatory nystagmic response. Three reference sources
      were used to assess the efficacy of this management: vestibulospinal function
      tests: pre- and post-treatment results at the Romberg test, the Unterberger
      Fukuda stepping test, the Babinski-Weil test, and gait testing with eyes closed;
      rotational tests: pre- and post-treatment results; and the self-perceived impact
      of vertigo: assessed by the Dizziness Handicap Inventory (DHI) and a scale based
      on the guidelines of the Japanese Society of Equilibrium Research (JSER, 1993).
      The JSER scale provides quantitative vertigo evaluation; the DHI reflects the
      patient's perceptual evaluation of handicap. RESULTS: Patients required 11
      sessions (mean value) to attain subjective improvement. Of the 23 patients, only
      seven required optokinetic stimulation (mean requirement: three sessions).
      Rotational tests and dynamic tests of the vestibulospinal function improved. The
      DHI and JSER results show that patients' post-rehabilitation perceptual
      evaluation significantly improved. CONCLUSION: The objective and subjective
      measures of disequilibrium in patients with unilateral Meniere's syndrome were
      significantly improved.

PMID- 14642676
TI  - Choice of prosthetic heart valves:update for the next generation.
AB  - Intervention for valvular heart disease poses unique clinical challenges in
      cardiology because the diseases are of relatively low prevalence, the
      interventions do not lend themselves to randomized comparative trials, and
      important clinical end points are assessed only after decades of follow-up. In
      addition, continuing advances in prosthetic heart valve technology make follow-up
      a moving target because long-term data by definition are available only for older
      prostheses. Newer tissue and mechanical prostheses afford superior hemodynamics
      compared with their older counterparts, and data suggest that durability and
      patient mortality are superior with newer compared with older bioprostheses.
      Arbitrary cutoffs dictating valve choice based predominantly on patient age may
      not give appropriate weight to individual patient perspectives. In educating and
      counseling patients regarding choices in heart valve prostheses, the clinician
      should help the patient weigh the relative merits for the individual patient of
      projected mortality, valve durability, and requirement for anticoagulation, with
      associated freedom from re-operation, hemorrhagic and thromboembolic risk, and
      impact on lifestyle.

PMID- 14642677
TI  - The next generation of prosthetic heart valves needs a proven track record of
      patient outcomes at > or =15 to 20 years.
AB  - Currently, a selection of good, albeit not perfect, prosthetic heart valves
      (PHVs) with data on patient outcomes with follow-up times of 15 to 20 years or
      longer is available. The "next generation" of PHVs have some interesting
      features, but there are no data on patient outcomes at > or =15 to 20 years. The
      history of PHVs is that: 1) major advances have come in small increments, and 2)
      extrapolations made from early results were not correct at long term, and when
      this occurred, patients paid the price in terms of mortality and morbidity. Thus,
      great enthusiasm from early results and premature prediction may be
      inappropriate. The data on long-term outcomes are needed and in 2003 one should
      preferentially select a PHV with proven long-term results.

PMID- 14642678
TI  - Validation of Mayo Clinic risk adjustment model for in-hospital complications
      after percutaneous coronary interventions, using the National Heart, Lung, and
      Blood Institute dynamic registry.
AB  - OBJECTIVES: We sought to validate the recently proposed Mayo Clinic risk score
      model for complications after percutaneous coronary interventions (PCI), using an
      independent data set. BACKGROUND: The Mayo Clinic risk score has eight simple
      clinical and angiographic variables for the prediction of complications defined
      as either death, Q-wave myocardial infarction, emergent or urgent coronary artery
      bypass graft surgery, or cerebrovascular accident after PCI. External validation
      using an independent data set is lacking. METHODS: A total of 3,264 patients
      undergoing PCI at each of the 17 sites in the National Heart, Lung, and Blood
      Institute's Dynamic Registry during two enrollment periods (July 1997 to February
      1998 and February to June 1999) were studied. Logistic regression was used to
      model the calculated risk score and major procedural complications. The expected
      number of complications, with 95% confidence bounds (CBs), was also calculated.
      RESULTS: There were 96 (2.94%) observed procedural complications, and the Mayo
      Clinic risk score predicted 93.5 events (2.86%; 95% CB 2.32% to 3.41%; p = NS).
      The Hosmer-Lemeshow goodness-of-fit p value was 0.28, and the area under the
      receiver operating curve was 0.76, indicating excellent overall discrimination.
      There were no statistical differences between observed and predicted procedural
      complications using the Mayo Clinic risk score among the most selected high- and
      low-risk subgroups. CONCLUSIONS: Eight variables were combined into a convenient
      risk scoring system that accurately predicts cardiovascular complications after
      PCI. The Mayo clinic predictive model for procedural complications yielded
      excellent results when applied to a multi-center external data set.

PMID- 14642679
TI  - Risk score for percutaneous coronary intervention: forewarned is forearmed.

PMID- 14642680
TI  - Arterial remodeling patterns before intervention predict diffuse in-stent
      restenosis: an intravascular ultrasound study.
AB  - OBJECTIVES: The aim of this retrospective study was to determine the predictors
      of diffuse in-stent restenosis (ISR) among the lesions causing the first ISR by
      intravascular ultrasound (IVUS) studies. BACKGROUND: Although some predictors of
      diffuse ISR have been reported, parameters on IVUS relating to diffuse ISR are
      not well characterized. METHODS: We classified 52 ISR lesions that had undergone
      successful stent implantation and led to restenosis into two types--focal and
      diffuse ISR--using quantitative coronary angiography. Restenosis was defined as >
      or =50% diameter stenosis, and diffuse ISR as lesion length > or =10 mm at follow
      up. The remodeling index (RI) was defined as the vessel area at the target lesion
      divided by that of averaged reference segments. RESULTS: There were no
      significant differences in patient, angiographic, and procedural characteristics
      between the focal (n = 25) and diffuse (n = 27) ISR groups. Baseline RI was
      significantly greater in the diffuse ISR group (1.03 +/- 0.18 vs. 0.88 +/- 0.24,
      p = 0.0159). Negative remodeling, defined as RI <0.9, was detected in 60% of the
      focal ISR group and in only 26% of the diffuse ISR group. By logistic regression
      analysis, baseline RI was the only independent predictor of diffuse ISR (p =
      0.0341). Moreover, volumetric analyses revealed that lesions developing into
      diffuse ISR had less capacity to compensate for further plaque growth.
      CONCLUSIONS: Among the first ISR lesions, baseline positive remodeling was the
      most powerful predictor of diffuse ISR. Measuring pre-interventional arterial
      remodeling patterns by IVUS may be helpful to stratify lesions at higher risk.

PMID- 14642681
TI  - Clinical and angiographic correlates and outcomes of suboptimal coronary flow
      inpatients with acute myocardial infarction undergoing primary percutaneous
      coronary intervention.
AB  - OBJECTIVES: The purpose of this study was to determine the clinical and
      angiographic correlates and outcomes of patients with suboptimal coronary flow
      after primary percutaneous coronary interventions (PCI). BACKGROUND: The clinical
      and angiographic correlates and outcomes of Thrombolysis in Myocardial Infarction
      (TIMI) < or =2 flow in patients treated with primary PCI are not known. METHODS:
      We evaluated 3,362 patients with ST elevation myocardial infarction enrolled in
      various Primary Angioplasty in Myocardial Infarction trials, who underwent
      primary PCI. RESULTS: Post-procedural final TIMI < or =2 flow occurred in 232
      (6.9%) patients. Multivariate analysis identified age > or =70 years (odds ratio
      [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), diabetes (OR 1.9; 95% CI,
      1.3 to 2.7), symptom onset to emergency room presentation (OR 1.1; 95% CI, 1.1 to
      1.2); initial TIMI < or =1 flow (OR 3.2; 95% CI, 1.9 to 5.5), and left
      ventricular ejection fraction <50% (OR 1.7; 95% CI, 1.2 to 2.4) as independent
      correlates of final TIMI < or =2 flow. In-hospital (composite of reinfarction,
      ischemic target vessel revascularization, or death, as well as these events
      individually) and one-year (reinfarction and/or death) events occurred more
      frequently in patients with TIMI < or =2 flow. The Cox proportional hazards model
      identified TIMI < or =2 flow to be independently associated with one-year
      mortality (hazard ratio 3.8, 95% CI, 2.5 to 5.7). CONCLUSIONS: Final TIMI < or =2
      flow, although uncommon after primary PCI, was strongly associated with hospital
      and one-year adverse events. The clustering of final TIMI < or =2 flow in high
      risk groups may partially explain the poor prognosis of these patients. Awareness
      of these risk factors may be useful to clinicians to triage and treat patients
      undergoing primary PCI.

PMID- 14642682
TI  - Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction
      and inflammatory markers in patients with coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to determine whether selective
      cyclooxygenase-2 (COX-2) inhibition with rofecoxib can modulate endothelial
      dysfunction and levels of circulating inflammatory markers in patients with
      established coronary artery disease (CAD). BACKGROUND: Expression of COX-2 is
      upregulated in atherosclerosis. Thus, it has been hypothesized that COX-2 may
      contribute to atherogenesis by producing eicosanoids, which mediate vascular
      inflammation and endothelial dysfunction. METHODS: In a randomized, double-blind,
      placebo-controlled, parallel-design trial, we studied the vascular effects of
      rofecoxib on brachial artery vasoreactivity and inflammatory markers in 60
      patients with angiographically proven CAD who were taking concomitant low-dose
      aspirin. Patients were randomly assigned to receive either rofecoxib (25 mg/day;
      n = 30) or placebo (n = 30) for eight weeks. Brachial artery endothelium
      dependent flow-mediated dilation (FMD), endothelium-independent nitroglycerin
      mediated dilation (NMD), and inflammatory markers (i.e., high-sensitivity C
      reactive protein [CRP], soluble intercellular adhesion molecule-1 [sICAM-1], and
      soluble interleukin-6 receptor [sIL-6r]) were measured at baseline and after
      eight-week follow-up. RESULTS: Baseline clinical characteristics were similar in
      the two groups. After eight weeks of treatment, FMD did not significantly change
      in either the rofecoxib or placebo group (4.0 +/- 3.0% to 4.0 +/- 3.8% vs. 2.7 +/
      2.7% to 3.1 +/- 2.7%, respectively; p = 0.6 by two-way analysis of variance).
      Similarly, NMD remained unchanged in both groups. Levels of CRP, sICAM-1, and sIL
      6r were not significantly altered in either the rofecoxib or placebo group.
      CONCLUSIONS: The addition of selective COX-2 inhibition with rofecoxib did not
      appear to have any favorable or adverse effects on endothelial dysfunction or
      vascular inflammation in patients with CAD using concomitant low-dose aspirin.

PMID- 14642683
TI  - Coxibs and the endothelium.

PMID- 14642684
TI  - The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma
      agonist, on markers of endothelial cell activation, C-reactive protein, and
      fibrinogen levels in non-diabetic coronary artery disease patients.
AB  - OBJECTIVES: We sought to assess the effect of rosiglitazone on markers of
      endothelial cell activation and acute-phase reactants in non-diabetic patients
      with coronary artery disease (CAD). BACKGROUND: Inflammation plays a key role in
      all stages of atherosclerosis and in the genesis of acute coronary syndromes.
      Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, is
      used in the treatment of type 2 diabetes mellitus, and previous data suggest that
      it may have anti-inflammatory effects on atherosclerosis. METHODS: Patients with
      stable, angiographically documented CAD without diabetes mellitus were
      investigated. Patients were randomized in a double-blind manner to receive
      treatment with placebo or rosiglitazone (4 mg/day for 8 weeks followed by 8
      mg/day for 4 weeks) for 12 weeks. Eighty-four patients completed the study.
      Fasting glucose, insulin, lipid profile, markers of endothelial activation, and
      inflammatory markers were measured at baseline and after 12 weeks. RESULTS:
      Rosiglitazone treatment resulted in a significant reduction in E-selectin (p =
      0.03), von Willebrand factor (p = 0.007), C-reactive protein (p < 0.001),
      fibrinogen (p = 0.003) and the homeostasis model of insulin resistance index (p =
      0.02), compared with placebo. Significant elevations in low-density lipoprotein
      and triglyceride levels were observed in the rosiglitazone group (p < 0.01).
      Within the rosiglitazone-treated group, reductions in C-reactive protein and von
      Willebrand factor were significantly correlated with a reduction in insulin
      resistance. CONCLUSIONS: Rosiglitazone significantly reduces markers of
      endothelial cell activation and levels of acute-phase reactants in CAD patients
      without diabetes. Potential underlying mechanisms include insulin sensitization
      and direct modification of transcription within the vessel wall.

PMID- 14642685
TI  - Peroxisome proliferator-activated receptors as therapeutic targets in
      inflammation.

PMID- 14642686
TI  - Heart rate variability and cardiac troponin I are incremental and independent
      predictors of one-year all-cause mortality after major noncardiac surgery in
      patients at risk of coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to determine whether perioperative
      measurements of heart rate variability (HRV) and cardiac troponin I (cTnI) add
      additional prognostic information to established risk scores for first-year
      mortality in patients at risk of coronary artery disease (CAD) undergoing major
      noncardiac surgery. BACKGROUND: In cardiac-risk patients undergoing major
      noncardiac surgery, the short- and long-term prognoses are mainly influenced by
      perioperative cardiac complications. Heart rate variability and cTnI are
      important prognostic markers in patients with congestive heart failure and
      myocardial infarction. METHODS: In a prospective study, 173 patients with CAD or
      at high risk of CAD undergoing major noncardiac surgery were followed up for one
      year. The main outcome measure was all-cause mortality. In addition to clinical
      parameters and established risk scores, HRV and cTnI were assessed
      perioperatively. RESULTS: Twenty-eight (16%) patients died within one year.
      Multivariate logistic regression analysis revealed three findings that were
      independently associated with death within the first year after surgery: the
      revised cardiac risk index (odds ratio 6.2 [95% confidence interval 1.6 to 25],
      depressed HRV before induction of anesthesia (16.2 [2.8 to 94]), and elevation of
      cTnI on postoperative day 1 or 2 (9.8 [3.0 to 32]). CONCLUSIONS: Depressed HRV
      before induction of anesthesia and elevated cTnI postoperatively are independent
      and powerful predictors of one-year mortality for patients at risk of CAD
      undergoing major noncardiac surgery and add incremental prognostic information to
      established risk scores that only consider preoperative information.

PMID- 14642687
TI  - A new oral therapy for long QT syndrome: long-term oral potassium improves
      repolarization in patients with HERG mutations.
AB  - OBJECTIVES: We sought to determine whether oral potassium supplementation safely
      increases serum K(+) and results in sustained improvement of repolarization
      parameters in long QT syndrome type 2 (LQT2) subjects. BACKGROUND: Mutations in
      HERG (LQT2), the gene encoding the rapid delayed rectifier K(+) current I(Kr),
      account for a significant proportion of congenital long QT syndrome (LQTS). The
      magnitude of I(Kr) is paradoxically increased by an increase in extracellular
      K(+). We tested the hypothesis that long-term oral potassium supplementation
      results in a mild, sustainable increase in serum K(+) that improves
      repolarization abnormalities in subjects with LQT2. METHODS: After an initial
      evaluation consisting of electrocardiography, electrolytes, blood urea nitrogen,
      and creatinine, escalating doses of potassium chloride (KCl) and spironolactone
      were administered to eight subjects with six distinct HERG mutations. Medications
      were continued for four weeks, at which time, the final evaluation was
      undertaken. Beta-adrenergic blocking therapy was maintained. RESULTS: The
      subjects ranged in age from 11 to 52 years. The average daily KCl and
      spironolactone dose was 3.3 +/- 1.5 mEq/kg and 3.5 +/- 1.2 mg/kg, respectively,
      and this regimen resulted in an increase in serum K(+) from 4.0 +/- 0.3 to 5.2 +/
      0.3 mEq/l. There were no serious complications associated with therapy. The
      increase in serum K(+) resulted in a decrease in the corrected QT interval from
      526 +/- 94 to 423 +/- 36 ms (mean +/- SD; lead V(2)). Both QT dispersion and T
      wave morphology improved in most subjects. CONCLUSIONS: Long-term oral potassium
      administration increases serum K(+) in patients with LQT2. This can be achieved
      safely and results in improvement in repolarization. Further studies are
      warranted to determine whether this will reduce the incidence of life-threatening
      events in LQTS patients.

PMID- 14642688
TI  - Potassium and long QT syndrome: a new look at an old therapy.

PMID- 14642689
TI  - Expression of angiotensin II receptors in human left and right atrial tissue in
      atrial fibrillation with and without underlying mitral valve disease.
AB  - TIVES: We postulated a change of angiotensin II receptor subtype expression in
      patients with lone atrial fibrillation (AF) and AF with underlying mitral valve
      disease (MVD) both compared with sinus rhythm (SR). BACKGROUND: Atrial
      fibrillation is a progressive disease associated with electrical and structural
      remodeling. Angiotensin II (ANGII) is involved in the process of myocardial
      remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2
      (AT(1) and AT(2)). METHODS: Left atrial (LA) and right atrial (RA) tissue samples
      were obtained from patients with AF or SR with or without underlying MVD. The
      AT(1) and AT(2) protein levels were measured by quantitative Western blotting
      techniques. RESULTS: The AT(1) protein level in the LA was significantly
      increased in patients with AF (all forms) compared with SR (p < 0.05), whereas
      AT(2) expression was not significantly altered. Comparison of the subgroups
      revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or
      without MVD. Additionally, investigations of ANGII receptor subtypes in the RA
      did not exhibit any significant changes either in AT(1) or in AT(2) in patients
      with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor
      subtype expression in LA. CONCLUSIONS: Atrial fibrillation is associated with an
      up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the
      AT(2) expression in the atrium. Because we found an enhanced expression of
      AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of
      AF in the LA.

PMID- 14642690
TI  - Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure
      diagnosis in primary care: a randomized, controlled trial.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of amino
      terminal pro-brain natriuretic peptide (N-BNP) on the diagnostic accuracy of
      heart failure (HF) in primary care. BACKGROUND: The accurate diagnosis of
      patients with suspected HF presenting in primary care is difficult. Amino
      terminal pro-brain natriuretic peptide is present in high levels in cardiac
      dysfunction and may improve the diagnostic accuracy of HF in primary care.
      METHODS: The Natriuretic Peptides in the Community Study was a prospective,
      randomized controlled trial of the effect of N-BNP on the accuracy of HF
      diagnosis. Patients presenting to their general practitioner (GP) with symptoms
      of dyspnea and/or peripheral edema were included. The GPs formulated an initial
      diagnosis based on clinical assessment. All patients underwent a full cardiologic
      assessment that included echocardiography and N-BNP. Each patient was randomized
      to the BNP group (GP received the N-BNP result) or the control group (GP did not
      receive the N-BNP result). Patients were then reviewed by their GP, and their
      diagnosis was reviewed. The primary end point was the accuracy of the GPs'
      diagnoses compared with the panel standard. RESULTS: A total of 305 patients were
      included; mean age was 72 years, 65% were female. Seventy-seven patients met the
      panel criteria for HF. The diagnostic accuracy improved 21% in the BNP group and
      8% in the control group (p = 0.002). The main impact of N-BNP measurement on
      diagnostic accuracy was the GPs' correctly ruling out HF. The number needed to
      diagnose by N-BNP measurement was seven patients. CONCLUSION: This study
      demonstrates that N-BNP measurement significantly improves the diagnostic
      accuracy of HF by GPs over and above customary clinical review.

PMID- 14642691
TI  - Comparing symptoms of depression and anxiety as predictors of cardiac events and
      increased health care consumption after myocardial infarction.
AB  - OBJECTIVES: We sought to compare symptoms of depression and anxiety as predictors
      of incomplete recovery after a first myocardial infarction (MI). BACKGROUND:
      Depressive symptoms have been related to post-MI mortality and health care
      consumption, but little is known about the effect of anxiety. We wanted to
      examine the effect of emotional distress on health care consumption and whether
      depressive symptomatology is a better predictor of prognosis than anxiety.
      METHODS: Subjects were 318 men (mean age 58 years) who completed the depression,
      anxiety, and hostility scales from the 90-item symptom check list after they
      survived a first MI. RESULTS: After an average follow-up of 3.4 years, there were
      25 cardiac events (fatal or non-fatal MI). Symptoms of both depression (hazard
      ratio [HR] 2.32, 95% confidence interval [CI] 1.04 to 5.18; p = 0.039) and
      anxiety (HR 3.01, 95% CI 1.20 to 7.60; p = 0.019) were associated with cardiac
      events, adjusting for age, left ventricular ejection fraction, and use of
      antidepressants. However, a multivariate analysis including all three negative
      emotions indicated that symptoms of anxiety (HR 2.79, 95% CI 1.11 to 7.03; p =
      0.029) explained away the relationship between depressive symptoms and cardiac
      events. Regarding health care consumption, anxiety (OR 2.00, 95% CI 1.24 to 3.22;
      p = 0.005), but not depression/hostility, was a predictor of cardiac
      rehospitalization and frequent visits at the cardiac outpatient clinic.
      CONCLUSIONS: Symptoms of depression and anxiety were associated with cardiac
      events. Anxiety was an independent predictor of both cardiac events and increased
      health care consumption and accounted for the relationship between depressive
      symptoms and prognosis. Symptoms of anxiety need to be considered in the risk
      stratification and treatment of post-MI patients.

PMID- 14642692
TI  - Anxiety, depression, and prognosis after myocardial infarction: is there a causal
      association?

PMID- 14642693
TI  - Depressive symptoms are the strongest predictors of short-term declines in health
      status in patients with heart failure.
AB  - OBJECTIVES: The purpose of this study was to assess whether depressive symptoms
      are independently associated with changes in heart failure (HF)-specific health
      status. BACKGROUND: Depression is common in patients with HF, but the impact of
      depressive symptoms on the health status of these patients over time is unknown.
      METHODS: We conducted a multicenter prospective cohort study of outpatients with
      HF. Data from 460 patients who completed a baseline Medical Outcomes Study
      Depression Questionnaire and both a baseline and follow-up (6 +/- 2 weeks) Kansas
      City Cardiomyopathy Questionnaire (KCCQ) were analyzed. The KCCQ measures HF
      specific health status, including symptoms, physical and social function, and
      quality of life. Multivariable regression was used to evaluate depressive
      symptoms as a predictor of change in KCCQ scores, adjusting for baseline KCCQ
      scores and other patient variables. The primary outcome was change in KCCQ
      summary scores (range 0 to 100; higher scores indicate better health status; 5
      points is a clinically meaningful change). RESULTS: Approximately 30% (139/460)
      of the patients had significant depressive symptoms at baseline. Depressed
      patients had markedly lower baseline KCCQ summary scores (beta = -19.6; p <
      0.001). After adjustment for potential confounders, depressed patients were at
      risk for significant worsening of their HF symptoms, physical and social
      function, and quality of life (average change in KCCQ summary score = -7.1
      points; p < 0.001). Depressive symptoms were the strongest predictor of decline
      in health status in the multivariable models. CONCLUSIONS: Depressive symptoms
      are a strong predictor of short-term worsening of HF-specific health status. The
      recognition and treatment of depression may be an important component of HF care.

PMID- 14642694
TI  - Transient ischemic dilation ratio of the left ventricle is a significant
      predictor of future cardiac events in patients with otherwise normal myocardial
      perfusion SPECT.
AB  - OBJECTIVES: This study evaluated the prognostic value of transient ischemic
      dilation (TID) of the left ventricle (LV) in patients with normal stress
      myocardial perfusion single photon emission computed tomography (MPS).
      BACKGROUND: The prognostic value of TID in patients with an otherwise normal MPS
      has not been defined. METHODS: We identified 1,560 patients who had normal stress
      MPS (436 vasodilator and 1,124 exercise stress), and no rest LV enlargement
      (Population 1) and followed up for 2.30 +/- 0.67 years for hard events (HE)
      (cardiac death or myocardial infarction) and soft events (SE)
      (revascularization). Prediction of first HE or SE (total events [TE]) was
      evaluated by multivariable Cox analysis, which was also applied to a broader
      group of 2,037 patients (including patients with minimal defects (Population 2).
      RESULTS: In Population 1, there were 13 HE, 36 SE, and 42 TE. Patients in the
      highest TID quartile (TID > or =1.21) had a higher TE rate than others,
      regardless of stress type. By multivariable analysis, highest TID quartile was
      predictive of TE (p = 0.008). Other independent predictors of TE were age,
      typical angina, and diabetes. In Population 2, TID was also predictive of TE.
      CONCLUSIONS: An entirely normal stress MPS study does not always imply an
      excellent prognosis. In patients with otherwise normal MPS, TID is an independent
      and incremental prognostic marker of TE even after significant clinical variables
      -age, typical angina, and diabetes--are accounted for. When TID is present,
      caution in making low-risk prognostic statements may be warranted, especially in
      patients with typical angina, the elderly, and diabetics. Our findings also
      appear to apply to the broader population of "normal" MPS, which included
      patients with minimal perfusion defects.

PMID- 14642696
TI  - Therapy with nitrates: increasing evidence of vascular toxicity.

PMID- 14642695
TI  - Role for peroxynitrite in the inhibition of prostacyclin synthase in nitrate
      tolerance.
AB  - OBJECTIVES: We tested whether in vivo nitroglycerin (NTG) treatment causes
      tyrosine nitration of prostacyclin synthase (PGI(2)-S), one of the nitration
      targets of peroxynitrite, and whether this may contribute to nitrate tolerance.
      BACKGROUND: Long-term NTG therapy causes tolerance secondary to increased
      vasoconstrictor sensitivity and increased vascular formation of reactive oxygen
      species. Because NTG releases nitric oxide (NO), NTG-induced stimulation of
      superoxide production should increase vascular nitrotyrosine levels, compatible
      with increased formation of peroxynitrite, the reaction product from NO and
      superoxide. METHODS: New Zealand White rabbits and Wistar rats were treated with
      NTG (0.4 mg/h for 3 days). Tolerance was assessed with isometric tension studies.
      Vascular peroxynitrite levels were quantified with luminol-derived
      chemiluminescence (LDCL) and peroxynitrite scavengers, such as uric acid and
      ebselen. As a surrogate parameter for the assessment of the activity of cyclic
      guanosine monophosphate-dependent kinase-I (cGK-I; the final signaling pathway
      for NO), the phosphorylation of the vasodilator-stimulated phosphoprotein (P
      VASP) at serine 239 was analyzed. RESULTS: Nitroglycerin treatment increased
      LDCL, and the inhibitory effect of uric acid and ebselen on LDCL was augmented in
      tolerant rings. Immunoprecipitation of 3-nitrotyrosine-containing proteins and
      immunohistochemistry analysis identified PGI(2)-S as a tyrosine-nitrated protein.
      Accordingly, conversion of ((14)C)-PGH(2) into 6-keto-PGF(1 alpha) (=PGI(2)-S
      activity) was strongly inhibited. In vitro incubation of tolerant rings with
      ebselen and uric acid markedly increased the depressed P-VASP levels and improved
      NTG sensitivity of the tolerant vasculature. CONCLUSIONS: Nitroglycerin-induced
      vascular peroxynitrite formation inhibits the activity of PGI(2)-S as well as NO,
      cGMP, and cGK-I signaling, which may contribute to vascular dysfunction in the
      setting of tolerance.

PMID- 14642697
TI  - Nebivolol and its 4-keto derivative increase nitric oxide in endothelial cells by
      reducing its oxidative inactivation.
AB  - OBJECTIVES: The objective of the present study was to elucidate the vasodilator
      mechanisms of nebivolol, a high selective beta(1)-receptor antagonist with
      antioxidant properties. BACKGROUND: Oxidative inactivation of nitric oxide (NO)
      is regarded as an important cause of its decreased biological activity. METHODS:
      Oxidative stress was induced through the binding of oxidized (ox)-low-density
      lipoprotein (LDL) to its specific endothelial receptor, called "lectin-like
      oxidized LDL receptor-1" (LOX-1), in bovine and human endothelial cells and in
      Chinese hamster ovary cells stably expressing bovine LOX-1 (BLOX-1-CHO cells).
      Reactive oxygen species (ROS), superoxide (O(2)(*-)), and NO were measured in
      cells by flow cytometry. RESULTS: Nebivolol and its 4-keto derivative prevented
      in a dose-dependent manner the increase of ROS (p < 0.001) and O(2)(*-) (p <
      0.001) in bovine aortic endothelial cells (BAECs), human umbilical vein
      endothelial cells (HUVECs), and BLOX-1-CHO cells stimulated with ox-LDL. Atenolol
      had no effect. The incubation of HUVECs and BAECs with ox-LDL reduced basal and
      bradykinin-induced NO and nitrite concentration (p from <0.001 to <0.01).
      Nebivolol and its 4-keto derivative prevented the reduction of basal and
      stimulated NO and nitrite concentration (p from <0.001 to <0.01) while atenolol
      had no effect. The preincubation of BAECs with blocking anti-LOX-1 monoclonal
      antibody (LOX-1 mAb) significantly counteracted the effect of ox-LDL on
      stimulated generation of NO (p < 0.001), but the effect was significantly lower
      than that of nebivolol and its 4-keto derivative alone (p < 0.01). CONCLUSIONS:
      In conclusion, the findings of the present study indicate that nebivolol
      increases NO also by decreasing its oxidative inactivation.

PMID- 14642698
TI  - Involvement of reactive oxygen species in angiotensin II-induced endothelin-1
      gene expression in rat cardiac fibroblasts.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of angiotensin
      II (Ang II) on fibroblast proliferation and endothelin-1 (ET-1) gene induction,
      focusing especially on reactive oxygen species (ROS)-mediated signaling in
      cardiac fibroblasts. BACKGROUND: Angiotensin II increases ET-1 expression, which
      plays an important role in Ang II-induced fibroblast proliferation. Angiotensin
      II also stimulates ROS generation in cardiac fibroblasts. However, whether ROS
      are involved in Ang II-induced proliferation and ET-1 expression remains unknown.
      METHODS: Cultured neonatal rat cardiac fibroblasts were stimulated with Ang II,
      and then [(3)H]thymidine incorporation and the ET-1 gene expression were
      examined. We also examined the effects of antioxidants on Ang II-induced
      proliferation and mitogen-activated protein kinase (MAPK) phosphorylation to
      elucidate the redox-sensitive pathway in fibroblast proliferation and ET-1 gene
      expression. RESULTS: Both AT(1) receptor antagonist (losartan) and ET(A) receptor
      antagonist (BQ485) inhibited Ang II-increased DNA synthesis. Endothelin-1 gene
      was induced with Ang II as revealed by Northern blotting and promoter activity
      assay. Angiotensin II increased intracellular ROS levels, which were inhibited
      with losartan and antioxidants. Antioxidants further suppressed Ang II-induced ET
      1 gene expression, DNA synthesis, and MAPK phosphorylation. PD98059, but not
      SB203580, fully inhibited Ang II-induced ET-1 expression. Truncation and
      mutational analysis of the ET-1 gene promoter showed that AP-1 binding site was
      an important cis-element in Ang II-induced ET-1 gene expression. CONCLUSIONS: Our
      data suggest that ROS are involved in Ang II-induced proliferation and ET-1 gene
      expression. Our findings imply that the combination of AT(I) and ET(A) receptor
      antagonists plus antioxidants may be beneficial in preventing the formation of
      excessive cardiac fibrosis.

PMID- 14642699
TI  - Time course of the interaction between tadalafil and nitrates.
AB  - OBJECTIVES: This study was designed to determine the time course of nitrate
      interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half
      life (t(1/2)) of 17.5 h. BACKGROUND: The PDE5 inhibitors augment the blood
      pressure (BP)-lowering effects of nitrates, yet the time course of this
      interaction is unclear. Recent guidelines from the American College of
      Cardiology/American Heart Association recommend that nitrates be withheld for 24
      h after taking sildenafil (t(1/2) = 4 h). METHODS: Male subjects (n = 150)
      received seven consecutive daily doses of placebo or tadalafil (20 mg). On day 7
      and beyond, subjects received repeated doses of sublingual nitroglycerin (0.4 mg)
      after the last dose of placebo or tadalafil. After a 10- to 21-day washout
      period, subjects crossed over to either placebo or tadalafil, and nitrate dosing
      was repeated. RESULTS: In response to nitroglycerin at 4, 8, and 24 h, standing
      systolic BP fell below 85 mm Hg in more subjects on tadalafil compared with
      placebo (p < 0.05), with no difference in the response to nitroglycerin at 48,
      72, and 96 h (p > 0.2). Similar observations were made for standing diastolic BP
      <45 mm Hg, decrease in systolic BP >30 mm Hg, and decrease in diastolic BP >20 mm
      Hg. Nitroglycerin also evoked greater mean maximal decreases in standing systolic
      BP at 8 and 24 h after taking tadalafil versus placebo (p < 0.02), with no
      significant difference at 48, 72, or 96 h (p > 0.49). CONCLUSIONS: The
      hemodynamic interaction between tadalafil and sublingual nitroglycerin lasted 24
      h, but was not seen at 48 h and beyond. Similar to other PDE5 inhibitors,
      tadalafil should not be administered in combination with organic nitrates.

PMID- 14642700
TI  - Angiotensin-converting enzyme polymorphism (I/D) and coronary heart disease in
      young adults.

PMID- 14642703
TI  - "Send them to the library"?

PMID- 14642704
TI  - Medical complications of eating disorders: an update.

PMID- 14642705
TI  - Eating disorders in adolescent boys: a review of the adolescent and young adult
      literature.
AB  - Although a number of studies have investigated eating disorders in adolescence
      and the topic has been thoroughly reviewed, these studies have typically focused
      on females, only to state that the approach and treatment should be similar in
      males. Recently, there have been a number of studies that have explored gender
      differences in eating disorders. In this article, we review the literature
      pertaining to two DSM-IV-defined disorders (anorexia nervosa and bulimia
      nervosa), a DSM-IV-defined research disorder (binge eating disorder), and two DSM
      PC-defined disorders (dieting/body image and purging/binge-eating behaviors),
      highlighting those findings that pertain to disordered eating in adolescent boys.

PMID- 14642706
TI  - Assessment of factors affecting the validity of self-reported health-risk
      behavior among adolescents: evidence from the scientific literature.
AB  - We reviewed the existing empirical literature to assess cognitive and situational
      factors that may affect the validity of adolescents' self-reports of alcohol and
      other drug use, tobacco use, behaviors related to unintentional injuries and
      violence, dietary behaviors, physical activity, and sexual behavior.
      Specifically, we searched for peer-reviewed journal articles published in 1980 or
      later that examined the factors affecting self-report of the six categories of
      behavior listed above. We also searched for studies describing objective measures
      for each behavior. Self-reports of each of six types of health-risk behaviors are
      affected by both cognitive and situational factors. These factors, however, do
      not threaten the validity of self-reports of each type of behavior equally. The
      importance of assessing health-risk behaviors as part of research activities
      involving adolescents necessitates the use of self-report measures. Researchers
      should familiarize themselves with the threats to validity inherent in this type
      of assessment and design research that minimizes these threats as much as
      possible.

PMID- 14642707
TI  - Perceptions of the at-risk nonsmoker: are potential intervention topics being
      overlooked?
AB  - This study assesses how adolescent nonsmokers, at-risk smokers, and smokers
      differ in perceptions of smoking harms, benefits, and safety. While small
      differences exist when comparing attitudes and knowledge concerning short- and
      long-term benefits of smoking, large differences arise when attitudes and
      knowledge concerning the short-term benefits and the safety of casual smoking are
      compared.

PMID- 14642708
TI  - Validation of the Perkins Adolescent Risk Screen (PARS).
AB  - PURPOSE: To examine the initial psychometric properties for the PARS, a brief
      interview used to screen for 16 items of adolescent risk and protective factors.
      METHODS: Participants included 193 adolescents, attending public middle and high
      schools or a university-based Adolescent Clinic. Participants completed a PARS
      interview, as well as a battery of questionnaires. Approximately 31% of
      participants received a second PARS interview from an independent rater to assess
      inter-rater consistency. RESULTS: Descriptive statistics revealed that
      participants, on average, were rated as low to moderate risk for health-related
      difficulties across all PARS items. Descriptive statistics also showed important
      risk patterns in this sample of adolescents (e.g., 1/5 of sample not exercising
      at all). Factor analysis yielded a total of five factors (Risk Factors,
      Protection Factors, Relationships/Mood, Motivation Issues, Weight Issues),
      accounting for 58% of the variance in PARS item scores. Satisfactory levels of
      internal consistency and inter-rater agreement for the PARS score were found.
      Convergent and divergent validity of PARS scores were supported by correlations
      obtained with similar and dissimilar measures, respectively. A significant age
      group difference was obtained in the total PARS score, with adolescents aged 17
      19 years obtaining higher scores than did adolescents aged 14-16 years. No
      significant gender differences were found. CONCLUSIONS: Our results support the
      initial psychometric properties (i.e., reliability, validity) of the PARS as a
      measure of health risk and protective factors in adolescents. The PARS is a
      brief, efficient means of obtaining important health risk information from
      adolescents throughout periodic routine health care visits.

PMID- 14642709
TI  - High school students' attitudes about firearms policies.
AB  - PURPOSE: To examine high school students' attitudes about firearm policies and to
      compare their attitudes with those of adults. METHODS: The Hamilton Youth and
      Guns Poll is the first national survey of high school students about their
      attitudes concerning firearm policies. Questions were asked of 1005 sophomores,
      juniors, and seniors about their actual (i.e., direct) exposure (e.g., presence
      of a gun in the home) and about their social (i.e., indirect) exposure (e.g.,
      whether the student could get a gun) to firearms and related violence. Population
      weights were applied, and multivariate logistic regression was used to examine
      the relationship between demographic and exposure variables and opinions about
      firearm policies. RESULTS: Most high school students supported more restrictive
      firearm policies. Opinions varied little by demographic variables with the
      exception of gender. Females were significantly more supportive of most firearm
      policies. Actual exposure was a more consistent predictor than social exposure.
      Students living in a home with a gun, particularly a handgun, were less likely to
      support most restrictive gun policies. CONCLUSIONS: Most high school students in
      the United States favor stringent policies governing firearms. Adolescents'
      attitudes about firearm policies parallel those of adults.

PMID- 14642710
TI  - Acculturation and the health and well-being of U.S. immigrant adolescents.
AB  - PURPOSE: To examine the association of acculturation, as measured by language
      spoken at home, with the health, psychosocial, school, and parental risk factors
      of adolescents of various racial/ethnic groups. METHODS: Using the U.S. component
      of the 1997-98 World Health Organization Study of Health Behavior in School
      Children, bivariate and multiple logistic regression analyses were conducted of
      records for adolescents in four racial/ethnic groups to explore the relationship
      between the language spoken at home and outcome variables regarding health status
      and risks, psychosocial and school risk factors, and parental factors. Data were
      analyzed using Software for the Statistical Analysis of Correlated Data (SUDAAN).
      RESULTS: Adolescents of all racial and ethnic groups who primarily speak a
      language other than English at home are at elevated risk for psychosocial risk
      factors such as alienation from classmates and being bullied, and parental risk
      factors such as feeling that their parents are not able or willing to help them.
      Those who speak a combination of languages are also at risk for being bullied and
      for high parental expectations. Language spoken at home is generally not
      associated with health and safety measures for adolescents across racial/ethnic
      groups. CONCLUSIONS: Adolescents whose primary language at home is not English
      experience higher psychosocial, school, and parental risks than non-Hispanic
      white English-speakers. New immigrant youths of all races and ethnic groups would
      potentially benefit from preventive and risk-reduction services.

PMID- 14642711
TI  - Adolescents and genetic testing: what do they think about it?
AB  - PURPOSE: To examine adolescents' attitudes toward screening for hereditary
      disorders. METHODS: A survey was distributed among 672 students in grades 10 to
      12 attending a public suburban high school. The first part of the survey
      consisted of information about three diseases: familial breast cancer, Tay-Sachs
      disease, and hypercholesterolemia. The second part was a questionnaire developed
      by the authors, which explored students' attitudes toward testing for these
      diseases. Comparisons between and within groups were performed using X2 analysis.
      RESULTS: Out of the 672 surveys distributed, 361 were returned (54% response
      rate). Mean age of participants was 17 +/- 1 years. Most girls (67%) wanted to be
      tested for familial breast cancer. Girls were significantly more willing than
      boys to be tested for Tay-Sachs disease (23% vs. 13%, p <.002) and for
      hypercholesterolemia (54% vs. 39%, p <.001). Girls who had a relative with breast
      cancer were significantly more willing to be tested than other girls (p <.05).
      Individuals in the ethnic risk groups for Tay-Sachs disease were significantly
      more willing to be tested than those not in the ethnic risk groups (p <.001).
      However, only 33% of those in the ethnic risk groups for Tay-Sachs disease stated
      that they would either "definitely" or "probably" wish to be tested. Students who
      had a family history of high cholesterol were significantly more willing to be
      tested than those without a family history (70% vs. 34%, p <.0001). About 81% of
      the students with a family history of high cholesterol had never been referred
      for cholesterol testing. Only about 25% of participants stated that their
      attitude toward genetic testing was affected by concerns that genetic information
      might be misused by insurance companies/employers. CONCLUSIONS: The main
      motivator for genetic testing is having someone in the family affected by the
      disease in question. Adolescent girls are more willing to be tested for genetic
      diseases than are boys.

PMID- 14642712
TI  - Eating disorders in adolescents: position paper of the Society for Adolescent
      Medicine.

PMID- 14642713
TI  - The Kaprun cable car fire disaster--aspects of forensic organisation following a
      mass fatality with 155 victims.
AB  - In November 2000, a tunnel-bound cable car in Kaprun caught fire, with the
      subsequent death of 155 persons. No passenger list was in existence and bodies
      were burnt to such an extent that morphological identification was not feasible.
      A full post-mortem examination was performed on all bodies. All bodies were
      positively identified within 19 days after the incident by DNA analysis. Cause of
      death was determined to be carbon monoxide poisoning in combination with
      suffocation due to inhalation of smoke. The organisational aspects of processing
      are portrayed.

PMID- 14642714
TI  - Image-guided virtual autopsy findings of gunshot victims performed with multi
      slice computed tomography and magnetic resonance imaging and subsequent
      correlation between radiology and autopsy findings.
AB  - Because the use of radiology in modern forensic medicine has been, until today,
      mostly restricted to conventional X-rays, which reduces a 3D body to a 2D
      projection, a detailed 3D documentation of a gunshot's wound ballistic effects
      was not possible. The aim of our study was to evaluate whether the progress in
      imaging techniques over the last years has made it possible to establish an
      observer-independent and reproducible forensic assessment using multi-slice
      computed tomography (MSCT) and magnetic resonance imaging (MRI) technologies for
      the documentation and analysis of gunshot wounds. The bodies of eight gunshot
      victims were scanned by MSCT and by MRI; the data of these imaging techniques
      were post-processed on a workstation, interpreted and subsequently correlated
      with the findings of classical autopsy. With the spiral CT and MRI examinations
      and the subsequent 2D multi-planar reformation (MPR) and 3D shaded surface
      display (SSD) reconstruction, the entire gunshot-created complex skull fractures
      and brain injuries (such as wound channels and deeply-driven bone splinters)
      could be documented in complete and graphic detail. CT and MRI also documented
      vital reaction to the gunshot by demonstrating air emboli in the heart and blood
      vessels and the classic pattern of blood aspiration to the lung. Gunshot residues
      deposited within and under the skin were visible. In conclusion, we think that
      the radiological methods of MSCT and MRI have the potential to become a routine
      "virtual autopsy" tool in the future. Bullets and relevant histological samples
      from specific sites then might be won in image-guided minimally invasive fashion
      via percutaneous biopsy. The rapid application of developing radiological methods
      may lead to new horizons in forensic documentation and intravital as well as
      postmortem examination.

PMID- 14642715
TI  - Optimized conditions for simultaneous determination of opiates, cocaine and
      benzoylecgonine in hair samples by GC--MS.
AB  - The present paper describes a qualitative and quantitative method for the
      simultaneous detection of opiates, cocaine and benzoylecgonine from human hair
      samples. Every step of the analytical procedure was studied to find the optimized
      conditions. Nine different incubation systems were examined. The influence of
      different pH values of samples on the isolation of analytes from the incubation
      media by Bond Elut cartridges and the stability of the compounds of interest in
      the different incubation media and conditions were investigated. The extracting
      power of different incubation media was studied as well. The phosphate buffer 0.1
      N at pH 5 was chosen as the extraction medium in an optimized procedure for
      simultaneous determination of opiates, cocaine and benzoylecgonine in hair
      samples. The method developed was validated. Recoveries were 90% for morphine
      (M), 81% for 6-monoacetylmorphine (6-AM), 90% for codeine (CD), 86% for cocaine
      (C) and 90% for benzoylecgonine (BE). Relative standard deviation for inter-day
      precision was better than 12%. The limits of detection resulted as 0.05 ng/mg for
      M and C, as 0.08 for 6-AM and as 0.2 ng/mg for BE. Forty hair samples collected
      from drug abusers admitted to centers for detoxification treatment were analyzed
      obtaining 23 positive results for opiates and/or cocaine. Twelve hair specimens
      longer than 10 cm were analyzed following a sectional approach. In the six
      positive cases, it was interesting to find that the 6-AM/M ratio generally
      decreased for each sample from the proximal segment to the distal segments.
      Moreover, the 6-AM/M ratio was generally lower than 1 in the intermediate and
      distal segments.

PMID- 14642716
TI  - The persistence of human scalp hair on clothing fabrics.
AB  - This study reports the persistence behaviour of human scalp hairs under a number
      of different circumstances. The effects of artificial dyeing of hairs, the
      presence or absence of roots and different types of fabrics on the persistence of
      hair on a variety of garments were investigated. The garments were made from
      cotton, polycotton, cotton/acrylic, polyester and wool. The results indicated
      that neither artificial dyes nor the presence or absence of roots had
      statistically significant effects on the persistence of hair. In contrast, the
      type of fabric had a major impact and it was found that, generally, hairs persist
      longer on rougher fabrics. The rate of loss of hairs from non-woollen fabrics
      during normal wear was found to follow an exponential decay curve. In contrast,
      the rate of loss from the woollen garments was quite linear, indicating a
      constant, even loss, and thus suggests that a different process is involved in
      the persistence of hairs on woollen garments from that on non-woollen garments.
      The speed at which hair was lost from fabrics decreased in the order polyester,
      cotton/acrylic, polycotton, cotton, smooth wool, rough wool, so that wool gives
      the best chance of recovering samples of hair. Due to the uniqueness of each
      case, it is advised that caution be used when making any interpretations and
      before drawing any conclusions.

PMID- 14642717
TI  - Cell line DNA typing in forensic genetics--the necessity of reliable standards.
AB  - The incorporation of reference DNA is crucial to the validation of any DNA typing
      protocol. This paper aims to provide a panel of reference DNAs for actual
      forensic profiling strategies, i.e. autosomal and gonosomal STR typing as well as
      mtDNA sequencing. We have characterised three human lymphoid cell lines, GM9947,
      GM9948 and GM3657, and considered 58 autosomal and gonosomal microsatellites as
      well as the mitochondrial control region sequence. Well-established markers and
      STRs recently developed for forensic use were involved. K562 DNA samples which we
      purchased from two different suppliers were also analysed. They revealed
      conflicting results with regard to the ChrX STR marker genotype. Hence, we
      suggest that K562 is no longer used for the calibration of profiling techniques.
      Our investigation establishes a panel of one female and two male DNA samples as
      an STR allelic ladder calibration tool and offers information on six alleles of
      each autosome (AS) marker, three alleles of each X chromosome (ChrX) marker and
      two alleles of each ChrY marker. In addition, sequences of the mitochondrial
      control region of the three DNAs are communicated in order to provide sequencing
      quality control.

PMID- 14642718
TI  - The evaluation of a synthetic long bone structure as a substitute for human
      tissue in gunshot experiments.
AB  - Our goal was to compare experimental gunshot wounds in our non-biological bone
      model with similarly created wounds in swine bones, and evaluate the results. The
      design of the synthetic (polyurethane) bone was patterned after human bone
      structure, with a compact outer layer covering a porous inner layer. Ordnance
      gelatin, as substitute bone marrow, was injected into the bone's hollow core. To
      simulate the periostium, the bone was covered with a layer of latex. Then the
      bone was embedded in gelatin used to simulate surrounding soft tissue. For
      comparison, fresh swine bones were also embedded in gelatin, and fired upon under
      the same guidelines. All gunshots were high-speed filmed. In our experimental
      study, gunshot wounds to swine bones, and to our synthetic, non-biological bones
      were compared. The results (the comparison between the biological swine bones and
      the non-biological model bones) in regard to the following points are absolutely
      equal: the loss of velocity and energy after striking bone, bone fragmentation,
      bullet deformation, and the penetrating wound channel. Continuing studies with
      our synthetic bone model will bring about an even greater understanding of the
      mechanisms of "bullet-bone interaction". For this reason, we have extended our
      variety of bone models to include other skeletal structures such as skull, spine,
      pelvis and flat bones for further gunshot experiments.

PMID- 14642719
TI  - Methods used for the killing and preservation of blowfly larvae, and their effect
      on post-mortem larval length.
AB  - A record of the length of the largest larvae collected from a corpse can be used
      to estimate the age of the oldest larvae present and, therefore, give an estimate
      of minimum time since death. Consequently, factors that affect post-mortem larval
      length will impact on any estimate of PMI based on it. Methods used to kill and
      preserve larvae are known to affect post-mortem length. This study looks at the
      effects of different preservatives, and variations in the protocol used for
      killing larvae by immersion in a hot water bath = [hot water killed; HWK], on the
      length of dead larvae of two common blowfly species. Post-feeding third instar
      Calliphora vomitoria and Lucilia sericata larvae were either HWK in boiling water
      and then placed in 80% ethanol or 10% formaldehyde solution, or placed live into
      the preservatives. For both species, choice of preservative and method of killing
      significantly affected post-mortem length. There were significant interspecific
      differences in their response to identical methods of killing and preservation.
      Additional experiments were carried out where C. vomitoria larvae were HWK in
      water at 80 and 100 degrees C for 1, 30, 60 and 90 s duration. Both temperature
      and duration significantly affected post-mortem length. Maximum length was
      attained after at least 60 s immersion. The amount of post-mortem decomposition
      that occurred after the larvae were placed in preservative could be greatly
      reduced by increasing the duration of immersion and/or increasing the water
      temperature. For the HWK larvae, it was possible to record their length
      immediately after death and before they had been placed in preservative. This
      data revealed that where 80% ethanol was used as a preservative the larvae
      expanded in the preservative. The timing of this expansion was investigated with
      a sample of C. vomitoria, HWK at 100 degrees C for 30 s and recording post-mortem
      length immediately after death and again after 3, 6, 9, 12, 24, 27, 30 and 33 h
      storage in 80% ethanol. Maximum length was recorded after 12 h storage and the
      rate of expansion was highest during the first 3 h in this preservative. After
      long-term storage (290 days), larvae killed and preserved in the same way were on
      average 0.7% longer than immediately after death and 0.6% (0.11 mm) smaller than
      when last measured (after 28 days storage).

PMID- 14642720
TI  - Subendocardial small infarct in the superior ventricular septum as a cause of
      sudden death.
AB  - In autopsy files from April 1999 to April 2001, five cases showed macroscopic
      subendocardial small infarct above 1 cm diameter in the superior ventricular
      septum (SVS) near the atrioventricular (AV) junction, and all five were finally
      considered to be sudden cardiac death after full investigation. All these small
      infarcts in these Japanese patients were located at the posterior site of the
      SVS, an area mainly nourished by branches which ramified from the AV node artery
      and which branched from the right coronary artery (RCA). Four of the five showed
      acute (A) or subacute (SA) foci in or around the healed (H) lesion and surviving
      myocytes were visible in infarcts, in all cases, which suggested a recurrent or
      chronic prolonged ischemia in the territory. Four of the five had a significant
      stenosis of the RCA and in the other one, there was an anomalous origin of the
      RCA. As all five had also small artery disease in the SVS, small infarct of the
      posterior SVS may have formed by hemodynamic impairment in the territory of the
      AV node artery caused by RCA disorders. We consider the evidence of macroscopic
      small infarct of the posterior SVS greatly aids in determining the cause of
      sudden death in forensic autopsy and may be notable lesion for discussing the
      pathogenesis of sudden cardiac death with RCA disorder.

PMID- 14642721
TI  - Gunshot residue patterns on skin in angled contact and near contact gunshot
      wounds.
AB  - The goal of this study was the reproduction of shape and pattern of gunshot
      residues in near contact and contact gunshot wounds by a series of experimental
      gunshots on a skin and soft tissue model. The aim was to investigate the shape
      and direction of soot deposits with regard to the muzzle according to different
      muzzle-target angles, firing distances, type of ammunition and weapon and barrel
      length. Based on a review of the literature and on the results of the experiments
      the authors could make the following statements of gunshot residues in angled
      contact and close contact gunshot: (1) gunshot residues on the target surface can
      be differentiated in a "inner" and "outer powder soot zone"; (2) the outer powder
      soot zone is much less visible than the inner powder soot zone and may lack on
      human skin; (3) with increasing muzzle target distance both inner and outer
      powder soot halo increase in size and decrease in density; (4) in angled shots
      the inner powder soot halo shows an eccentric, elliptic shape which points
      towards the muzzle, regardless of ammunition, calibre and barrel length; (5) the
      outer powder soot points away from the muzzle in angled contact and close contact
      shots.

PMID- 14642722
TI  - Multivariate chemometrics for the forensic discrimination of blue ball-point pen
      inks based on their Vis spectra.
AB  - Fifty blue ball-point pen inks of five different brands were examined on the
      basis of the Vis spectrum of their ethanolic solutions with a view to achieving
      good discrimination between them. Samples were dissolved in absolute ethanol and
      their absorbance values in the range of 400-750 nm, after appropriate
      transformations, were used as variables in the multivariate statistical
      techniques of cluster analysis (CA), principal component analysis (PCA) and
      discriminant analysis (DA). These techniques were used successively so that an
      effective and meaningful discriminant model was calculated in the final step. The
      initial 351 variables (log10 transformed ink absorption values at each
      wavelength) were subjected to a K-means CA over the objects (samples) and only 20
      variables were retained. Principal component analysis was used to detect any
      outliers (four samples were removed) and the remaining samples were re-subjected
      to PCA to decide how many variables to enter into DA and whether original
      variables or components should be used. It was found that the first three
      principal components (in accordance with the Kaiser criterion) were good
      descriptors of the 20 original variables (96.97% of the data variance was
      explained) and their use as latent variables in DA lead to low average variable
      redundancy (33.6%) in the discriminant model. The calculated model had a Wilks'
      lambda of 8.98 x 10(-5) and was statistically significant at the P = 0.05 level.
      The post hoc classification of the training dataset was 100% correct. From the DA
      results and the component loadings it was found that discrimination was achieved
      on the basis of differences in the shape of the absorption bands as well as their
      relative intensities. The method was therefore deemed appropriate for supporting
      exclusionary forensic purposes.

PMID- 14642723
TI  - Morphological and chemical analysis of magic mushrooms in Japan.
AB  - Morphological and toxicological analyses were performed on hallucinogenic
      mushrooms that are currently circulated in Japan. Scanning electron microscope
      (SEM) indicated a three-dimensional microstructures in the mushrooms. The
      complementary use of SEM with an optical microscope was effective for observing
      characteristic tissues, such as basidiomycetes, spores, cystidia and basidia.
      Hallucinogenic alkaloids were extracted with methanol and determined by high
      performance liquid chromatography (HPLC) with a UV detector set at 220 nm. The
      psilocin/psilocybin contents in Psilocybe cubensis were in the range of 0.14
      0.42%/0.37-1.30% in the whole mushroom (0.17-0.78%/0.44-1.35% in the cap and 0.09
      0.30%/0.05-1.27% in the stem), respectively. The hallucinogenic alkaloids in
      Copelandia were 0.43-0.76%/0.08-0.22% in the whole mushroom (0.64-0.74%/0.02
      0.22% in the cap and 0.31-0.78%/0.01-0.39% in the stem). It thus appears that P.
      cubensis is psilocybin-rich, whereas Copelandia is psilocin-rich.

PMID- 14642724
TI  - Growing cannabis with naphthalene in Rome.
AB  - A young Italian male was investigated for possession of illicit marijuana in
      Rome. In his house, police found 80 cannabis plants, the plants were different
      sizes and located in a room with ultraviolet light, naphthalene, as a grey-white
      powder, was also found in his house. The man indicated that he used it for
      cannabis cultivation.

PMID- 14642725
TI  - Quantification of RNA degradation by semi-quantitative duplex and competitive RT
      PCR: a possible indicator of the age of bloodstains?
AB  - In vitro RNA degradation is a complex and non-linear process which can serve as
      indicator for the quality and age of stains. We have developed a semi
      quantitative duplex reverse transcription-polymerase chain reaction (RT-PCR)
      assay which, in combination with competitive RT-PCR using an external standard,
      allows quantification of RNA degradation levels. Using this method, we have
      investigated 106 bloodstains stored up to 15 years. The distribution of the peak
      area quotients of standard and target messenger-RNA (mRNA) as measured by laser
      induced fluorescence capillary electrophoresis was closely correlated with the
      age of the samples. Further statistical analysis showed that bloodstains with age
      differences of 5 years and more exhibit statistical significant variances in peak
      area quotients of both housekeeping genes included in this study, beta-actin and
      cyclophilin. This can be of value when evidence from old cases is re
      investigated. Our data show, that, although RNA continues to be degraded in dried
      bloodstains, mRNA suitable for RT-PCR can be isolated from samples stored for at
      least 15 years.

PMID- 14642726
TI  - Co-amplification of ENFSI-loci D3S1358, D8S1179 and D18S51: validation of new
      primer sequences and allelic distribution among 2874 individuals.
AB  - The present communication presents a new triplex PCR co-amplifying three loci
      (D3S1358, D8S1179 and D18S51) recommended for STR typing by the European Network
      of Forensic Science Institutes (ENFSI). Twenty-two different primers were tested
      to optimise the PCR. Four of the six primer sequences finally chosen were self
      selected, the fifth was a published one and the sixth derived from a commercially
      available multiplex kit. Using this PCR-setup, even minimum amounts of genomic
      DNA are sufficient to analyse the STR loci D3S1358, D8S1179 and D18S51 in
      parallel. Especially in forensic casework, where DNA is mostly limited and often
      contaminated with enzyme inhibitors, this new PCR proved to be very advantageous.
      To demonstrate the reliability, buccal swabs from 2874 persons were typed not
      only with the new triplex PCR but also with a commercially available multiplex
      kit.

PMID- 14642727
TI  - An unusual fatal injury due to tyre burst: a case report.
AB  - A 20 year-old male driver of a heavy duty crane, employed in an industry located
      in an industrial area on the outskirts of Delhi was fatally injured while
      repositioning an ill-fitted locking rim of a crane tyre (Fig. 1). The inner tube
      of the crane tyre had accidentally burst, dislodging the loose iron-locking rim,
      which hit the individual with a great force resulting in multiple injuries. He
      died on his way to the hospital.

PMID- 14642728
TI  - Meckel's diverticulum and intestinal obstruction--report of a fatal case.
AB  - Meckel's diverticulum is an uncommon cause of intestinal obstruction in adult
      life. Rarely Meckel's diverticulum is complicated by a mesodiverticular band,
      which is believed to be a remnant of a vitelline artery. When this abnormality
      occurs it is associated with high mortality. We present a case of a 48-year-old
      man with increasing abdominal pain and vomiting for 3 days. Meckel's diverticulum
      was not taken into diagnostic consideration, and the man died. Autopsy revealed a
      Meckel's diverticulum with a mesodiverticular band and intestinal obstruction.
      Histological examination of cross sections of the mesodiverticular band showed
      the presence of an artery. Because of the high mortality of this rare anatomic
      anomaly in adults, we find the case of interest.

PMID- 14642729
TI  - Population data for 11 STR loci in northeast China Han.
AB  - Allele frequencies for the nine tetrameric short tandem repeats (STR) loci
      D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, and D7S820 (AmpFlSTR
      Profiler Plus PCR amplification kit, PE Applied Biosystems) and two pentameric
      STR loci Penta D and Penta E (PowerPlex 16 system, Promega Corporation) were
      determined in a population sample of unrelated China Han.

PMID- 14642730
TI  - STR data for the AmpFlSTR SGM Plus and Profiler loci from Taiwan.
AB  - Allele frequencies for the 15 STRs included in the AmpFlSTR SGM Plus and Profiler
      kit (D3S1358, VWA, D16S539, D2S1338, D8S1179, D21S11, D18S51, D19S433, THO1, FGA,
      TPOX, CSF1PO, D5S818, D13S317 and D7S820) were obtained from a sample of 597
      unrelated individuals living in Taiwan. All loci, except for D8S1179 and D5S818,
      are in Hardy-Weinberg equilibrium.

PMID- 14642731
TI  - Y-chromosome STR haplotypes of Han ethnic group in Xi'an (NW China).
AB  - Allele and haplotype frequencies of six Y-chromosomal STR loci, namely DYS393,
      DYS19, DYS389II, DYS390, DYS391, and DYS385, were determined from 114 healthy
      unrelated males of Han ethnic group in Xi'an (NW China).

PMID- 14642732
TI  - Y chromosome STRs in Croatians.
AB  - Eight Y chromosome short tandem repeat (STR) polymorphisms (DYS19, DYS388,
      DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) were analyzed in the sample of
      457 unrelated Croatian men. A general STR allelic frequency pattern in Croatians
      corresponds to other European populations with the exception of the loci DYS19
      and DYS389II. The most frequent DYS19 allele was 16, while at the DYS389II the
      most frequent were alleles 30 and 31. The most frequent Y chromosome haplotype
      (16-13-13-31-24-11-11-13) was found in 33 individuals (7.22%). One hundred and
      seventy-four haplotypes (38.07%) were observed in single copies.

PMID- 14642733
TI  - STR Data for the AmpFlSTR Identifiler loci in three ethnic groups (Malay,
      Chinese, Indian) of the Malaysian population.
AB  - Allele frequencies for the 15 STR loci in the AmpFlSTR Identifiler kit were
      determined and compared for the three main ethnic groups of the Malaysian
      population comprising 210 Malays, 219 Chinese and 209 Indians. Blood was placed
      on FTA paper and DNA was purified in-situ.

PMID- 14642734
TI  - Environmental tobacco smoke in the workplace: markers of exposure, polymorphic
      enzymes and implications for disease state.
AB  - Studies focusing directly on tobacco smoke have tended to center on the
      differences in effect between smokers and non-smokers and many hundreds of such
      studies have been performed. In this review, we examine the current literature
      specifically concerning workplace exposure to environmental tobacco smoke (ETS)
      and its impact on individuals, particularly non-smokers and never smokers. The
      paper deals with quantifying and minimizing ETS exposures in a working
      environment, the effect of polymorphisms and other genetic factors that influence
      health outcomes after exposure to ETS and the association of occupational ETS
      exposure to disease-specific biomarkers.

PMID- 14642735
TI  - The inhibitory effects of flavonoids and antiestrogens on the Glut1 glucose
      transporter in human erythrocytes.
AB  - Flavonoids and isoflavonoids are potent inhibitors of glucose efflux in human
      erythrocytes. Net changes of sugars inside the cells were measured by right angle
      light scattering. The inhibitory potency of hydroxylated flavonoids depends on
      the pH of the medium. The apparent affinity is maximal at low pH where the
      molecule is in the undissociated form. The following K(i)-values at pH 6.5 in
      microM have been obtained: phloretin 0.37+/-0.03, myricetin 0.76+/-0.42,
      quercetin 0.93+/-0.28, kaempferol 1.33+/-0.17, isoliquiritigenin 1.96, genistein
      3.92+/-0.62, naringenin 8.88+/-1.88, 7-hydroxyflavone 17.58+/-3.15 and daidzein
      18.62+/-2.85. Flavonoids carrying hydroxyl groups are weak acids and are
      deprotonated at high pH-values. From spectral changes pK-values between 6.80
      (naringenin) and 7.73 (myricetin) have been calculated. No such pK-value could be
      obtained from quercetin which was rather unstable at alkaline pH. Flavone itself
      without a hydroxyl group does not demonstrate any absorbance changes at different
      pH-values and no significant change in inhibition of glucose transport with pH
      (K(i)-value around 35 microM). In this respect it is similar to the antiestrogens
      diethylstilbestrol, tamoxifen and cyclofenil with K(i)-values for glucose efflux
      inhibition of 2.61+/-0.30, 6.75+/-2.03 and 3.97+/-0.54 microM. Except for
      phloretin, the flavonoids investigated have planar structures. The inhibitory
      activity in glucose efflux of planar flavonoids increases exponentially with the
      number of hydroxyl groups in the molecule.

PMID- 14642736
TI  - Biotransformation of tamoxifen in a human endometrial explant culture model.
AB  - Although long-term tamoxifen therapy is associated with increased risk of
      endometrial cancer, little is known about the ability of endometrial tissue to
      biotransform tamoxifen to potentially reactive intermediates, capable of forming
      DNA adducts. The present study examined whether explant cultures of human
      endometrium provide a suitable in vitro model to investigate the tissue-specific
      biotransformation of tamoxifen. Fresh human endometrial tissue, microscopically
      uninvolved in disease, was cut into 1 x 2-mm uniform explants and incubated with
      media containing either 25 or 100 microM tamoxifen in a 24-well plate.
      Metabolites were analyzed by reversed-phase HPLC using postcolumn, online,
      photochemical activation and fluorescence detection. Three metabolites, namely,
      alpha-hydroxytamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen were
      identified in culture medium and tissue lysates. N-desmethyltamoxifen was found
      to be the major metabolite in both tissue and media extracts of tamoxifen-exposed
      explants. Incubations of tamoxifen with recombinant human cytochrome P-450s
      (CYPs) found that CYP2C9 and CYP2D6 produced all three of the above tamoxifen
      metabolites, while CYP1A1 and CYP3A4 catalyzed the formation of alpha
      hydroxytamoxifen and N-desmethyltamoxifen, and CYP1A2 and CYP1B1 only formed the
      alpha-hydroxy metabolite. CYP2D6 exhibited the greatest activity for the
      formation of all three tamoxifen metabolites. Western immunoblots of microsomes
      from human endometrium detected the presence of CYPs 2C9, 3A, 1A1 and 1B1 in
      fresh endometrium, while CYPs 2D6 and 1A2 were not detected. Immunohistochemical
      (IHC) analysis also confirmed the presence of CYPs 2C9, 3A and 1B1 in fresh human
      endometrium and in viable tissue cultured for 24 h with or without tamoxifen.
      Together, the results support the use of explant cultures of human endometrium as
      a suitable in vitro model to investigate the biotransformation of tamoxifen in
      this target tissue. In addition, the results support the role of CYPs 2C9, 3A,
      1A1 and 1B1 in the biotransformation of tamoxifen, including the formation of the
      DNA reactive alpha-hydroxytamoxifen metabolite, in human endometrium.

PMID- 14642737
TI  - Genetic alterations in the Catnb gene but not the H-ras gene in hepatocellular
      neoplasms and hepatoblastomas of B6C3F(1) mice following exposure to
      diethanolamine for 2 years.
AB  - The present study characterized the immunohistochemical localization of beta
      catenin protein in hepatocellular neoplasms and hepatoblastomas in B6C3F(1) mice
      exposed to diethanolamine (DEA) for 2 years and evaluated genetic alterations in
      the Catnb and H-ras genes which are known to play important roles in the
      pathogenesis of liver malignancies. Genomic DNA was isolated from paraffin
      sections of each liver tumor. Catnb exon 2 (corresponds to exon 3 in human)
      genetic alterations were identified in 18/18 (100%) hepatoblastomas from DEA
      exposed mice. Deletion mutations (15/18, 83%) were identified more frequently
      than point mutations (6/18, 33%) in hepatoblastomas. Eleven of 34 (32%)
      hepatocellular adenomas and carcinomas from DEA treated mice had mutations in
      exon 2 of the beta-catenin gene, while only 1 of 10 spontaneous neoplasms had a
      deletion mutation of codon 5-6. Common to all liver neoplasms (hepatocellular
      adenomas, carcinomas and hepatoblastomas) was membrane staining for the beta
      catenin protein, while cytoplasmic and nuclear staining was observed only in
      hepatoblastomas. The lack of H-ras mutations in hepatocellular neoplasms and
      hepatoblastomas suggests that the ras signal transduction pathway is not involved
      in the development of liver tumors following DEA exposure which is different from
      that of spontaneous liver tumors that often contain H-ras mutations.

PMID- 14642738
TI  - In vitro metabolism of zolmitriptan in rat cytochromes induced with beta
      naphthoflavone and the interaction between six drugs and zolmitriptan.
AB  - Zolmitriptan is a novel and highly selective 5-HT(1B/1D) receptor agonist used as
      an acute oral treatment for migraine. There are few reports regarding the in
      vitro metabolism of zolmitriptan. Previous studies indicated zolmitriptan was
      metabolized via CYP1A2 in human hepatic microsomes. In order to study the enzyme
      kinetics and drug interaction, the metabolism of zolmitriptan and possible drug
      drug interactions were investigated in rat hepatic microsomes induced with
      different inducers. An active metabolite, N-demethylzolmitriptan, was detected
      and another minor, inactive metabolite that was reported in human hepatic
      microsomes was not detected in this study. The enzyme kinetics for the formation
      of N-demethylzolmitriptan from zolmitriptan in rat liver microsomes pretreated
      with BNF were 96+/-22 microM (K(m)), 11+/-3 pmol min(-1)mg protein(-1) (V(max)),
      and 0.12+/-0.02 microl min(-1)mg protein(-1) (CL(int)). Fluvoxamine and
      diphenytriazol inhibited zolmitriptan N-demethylase activity catalyzed by CYP1A2
      (K(i)=3.8+/-0.3 and 3.2+/-0.1 microM, respectively). Diazepam and propranolol
      elicited a slight inhibitory effect on the metabolism of zolmitriptan (K(i)=70+/
      11 and 90+/-18 microM, respectively). Cimetidine and moclobemide produced no
      significant effect on the metabolism of zolmitriptan. Fluvoxamine yielded a
      k(inactivation) value of 0.16 min(-1), and K(i) of 57 microM. The results suggest
      that rat hepatic microsomes are a reasonable model to study the metabolism of
      zolmitriptan, although there is a difference in the amount of minor, inactive
      metabolites between human hepatic microsomes and rat liver microsomes. The
      results of the inhibition experiments provided information for the interactions
      between zolmitriptan and drugs co-administrated in clinic, and it is helpful to
      explain the drug-drug interactions of clinical relevance on enzyme level. This
      study aso demonstrated that fluvoxamine may be a mechanism-based inactivator of
      CYP1A2.

PMID- 14642740
TI  - Spectral interactions of tetrachlorobiphenyls with hepatic microsomal cytochrome
      p450 enzymes.
AB  - This study investigated the spectral interactions of hepatic microsomal
      cytochrome p450 (CYP) enzymes with four symmetrical polychlorinated biphenyls
      (PCBs): 2,2',4,4'-tetrachlorobiphenyl (PCB 47); 2,2',5,5'-tetrachlorobiphenyl
      (PCB 52); 2,2',6,6'-tetrachlorobiphenyl (PCB 54); and 3,3',4,4'
      tetrachlorobiphenyl (PCB 77). The PCBs were selected to explore structure
      activity relationships and the effect of the chlorination pattern on PCB-CYP
      spectral interactions. To examine CYP enzyme specificity, difference spectra were
      measured with hepatic microsomes prepared from control, phenobarbital (PB)-, 3
      methylcholanthrene (MC)-, and dexamethasone (DEX)-treated rats in the absence and
      presence of CYP-specific antibodies. The four PCB congeners elicited a type I
      spectral change with all hepatic microsomal preparations. The binding efficiency
      of the PCBs was highest with microsomes from PB-treated rats. The largest
      absorbance change and highest binding efficiency were observed with PCB 54, the
      most non-coplanar congener tested. Antibody inhibition and CYP immunoquantitation
      data showed that the PCBs bind to CYP1A, CYP2B, CYP2C and CYP3A enzymes to
      varying degrees. For example, PCB 47, 52, and 54 bind preferentially to CYP2B and
      to a lesser extent to CYP3A enzymes in microsomes from PB-treated male rats; PCB
      52 binds primarily to CYP3A enzymes in microsomes from DEX-treated female rats;
      and PCB 54 binds to CYP3A and to CYP2C enzymes in microsomes from control male
      rats. The study demonstrated that the extent of PCB-CYP binding interaction was
      dependent on the chlorination pattern of the PCB and on the relative abundance of
      individual CYP enzymes in hepatic microsomes.

PMID- 14642739
TI  - Effects of dietary soy and estrous cycle on adrenal cytochrome p450 1B1
      expression and DMBA metabolism in adrenal glands and livers in female Sprague
      Dawley rats.
AB  - Cytochrome p450 1B1 (CYP1B1) has been shown to be important in the bioactivation
      of 7,12-dimethylbenz[a]anthracene (DMBA) to an adrenal toxin in rats. We
      investigated the effects of diet and stage of estrous cycle on CYP1B1 expression
      in rat adrenal glands and on DMBA metabolism by rat adrenal and hepatic
      microsomes. Female Sprague-Dawley (SD) rats were placed on either standard soy
      containing NIH-31 rat chow or soy- and alfalfa-free 5K96 diet from postnatal day
      (PND) 21 until sacrifice at PND50+/-5. Stage of estrous at sacrifice was assessed
      by vaginal cytology and confirmed by histological examination of the vagina.
      Dietary soy at the level present in NIH-31 diet did not affect serum estrogen and
      progesterone levels. Immunohistochemical analysis confirmed that CYP1B1 was
      exclusively expressed in the zona fasciculata and zona reticularis in adrenal
      cortex, which are the regions vulnerable to DMBA-induced adrenal necrosis.
      Adrenal CYP1B1 protein expression, 3H-DMBA depletion, and formation of DMBA-3,4-,
      and -8,9-dihydrodiols by adrenal microsomes were greater in animals fed 5K96
      diet, and the stage of the estrous cycle affected these parameters only in the
      soy-free 5K96 diet. In hepatic microsomes, the formation of DMBA-3,4-dihydrodiol,
      7-hydroxy- and 12-hydroxy-DMBA were lower in animals fed NIH-31 diet than in
      those fed 5K96 diet. Thus, dietary soy and the estrous cycle appear to regulate
      adrenal CYP1B1 expression and DMBA metabolism by both adrenal and hepatic
      microsomes. The use of different basal diets containing variable levels of soy
      components may affect certain toxicity assessments.

PMID- 14642741
TI  - The effect of inducing agents on the metabolism of trypanocidal diamidines by
      isolated rat hepatocytes.
AB  - This study has investigated the effect of phenobarbitone (PB), 3
      methylcholanthrene (3-MC), and deltamethrin (DM) on the metabolism of two
      trypanocidal diamidines; pentamidine isethionate and diminazene aceturate in
      freshly isolated Sprague-Dawley rat hepatocytes. There were significant increases
      in the total cytochrome p450 content of hepatocytes obtained from rats pre
      treated with PB and 3-MC, whereas pre-treatment with DM did not produce any
      significant induction of cytochrome p450. However, pre-treatment of rats with
      each of the three agents led to inhibition of pentamidine metabolism following a
      3h incubation of pentamidine (100 microM) with freshly isolated rat hepatocytes
      (5 x 10(6) cells ml(-1)). Pre-treatment with 3-MC caused the highest inhibitory
      effect on pentamidine metabolism (8-fold inhibition), compared with PB (4.8-fold)
      and DM (2.2-fold). Six previously reported phase I metabolites of pentamidine
      were identified in cells from all the pre-treated animals as well as controls.
      When compared to the control group, there were significant differences between
      the profiles of the three major metabolites of pentamidine, 1,5-di(4'
      amidinophenoxy)-2-pentanol, 1,5-di(4'-amidinophenoxy)-3-pentanol and 5-(4'
      amidinophenoxy) pentanoic acid, in hepatocytes from the DM and 3-MC pre-treated
      rats, whereas no significant differences were observed in the cells from the PB
      pre-treated group. In contrast, diminazene was not metabolised with the same
      experimental conditions. Differences in the metabolic profiles of pentamidine and
      its metabolites as a result of concomitant exposure to environmental xenobiotics
      could have important toxicological and pharmacological implications for patients
      that receive the drug.

PMID- 14642742
TI  - A cost of disease resistance: paradigm or peculiarity?

PMID- 14642743
TI  - Tracing the dawn of Plasmodium falciparum with mitochondrial genome sequences.

PMID- 14642744
TI  - Diversity of retrotransposable elements in compact pufferfish genomes.

PMID- 14642745
TI  - Why are some human disease-associated mutations fixed in mice?

PMID- 14642746
TI  - Protein interaction: same network, different hubs.

PMID- 14642747
TI  - Arthropod and mollusk defensins--evolution by exon-shuffling.
AB  - Arthropod and mollusk defensins are secreted antibacterial proteins that exhibit
      similarity in sequence, mode of action and structure and are expressed
      ubiquitously. Comparison of the gene organization of a newly cloned scorpion
      defensin gene, with that of other arthropods and the mussel, revealed that all
      exons and introns, aside from the exon encoding the mature protein, differ widely
      in number, size and sequence. This variability suggests that the exon encoding
      the mature defensin has undergone exon-shuffling and integrated downstream of
      unrelated leader sequences during evolution. Unlike other exon-shuffling events,
      in which modules are added into existing proteins, arthropod and mollusk
      defensins represent the first instance of exon-shuffling of autonomous modules.

PMID- 14642748
TI  - Eukaryotic genes in Mycobacterium tuberculosis? Possible alternative
      explanations.

PMID- 14642749
TI  - Epidemiology, cancer genetics and microarrays: making correct inferences, using
      appropriate designs.

PMID- 14642750
TI  - The genome reduction hypothesis and the phylogeny of eukaryotes.

PMID- 14642751
TI  - Gradients and thresholds: BMP response gradients unveiled in Drosophila embryos.
AB  - Bone morphogenetic proteins (BMP) direct dorsal-ventral patterning in both
      invertebrate and vertebrate embryos, with strong evolutionary conservation of
      molecular components of the pathway. Dorsal-ventral patterning of the early
      Drosophila embryo is a powerful experimental system to probe mechanisms of BMP
      gradient formation and interpretation. Recent studies have found that spatial
      patterns of activated BMP signal transducers in Drosophila go through an
      unexpected transition: a shallow gradient of weak responses at mid
      cellularization changes to a step gradient of stronger responses in cellularized
      embryos. The transition between two gradients of different shape yields new
      insights into the progression of Drosophila dorsal-ventral patterning and raises
      new issues about the mechanisms of gradient formation.

PMID- 14642752
TI  - Mitochondrial genomes: anything goes.

PMID- 14642753
TI  - A decade of progress in plant molecular phylogenetics.
AB  - Over the past decade, botanists have produced several thousand phylogenetic
      analyses based on molecular data, with particular emphasis on sequencing rbcL,
      the plastid gene encoding the large subunit of Rubisco (ribulose bisphosphate
      carboxylase). Because phylogenetic trees retrieved from the three plant genomes
      (plastid, nuclear and mitochondrial) have been highly congruent, the "Angiosperm
      Phylogeny Group" has used these DNA-based phylogenetic trees to reclassify all
      families of flowering plants. However, in addition to taxonomy, these major
      phylogenetic efforts have also helped to define strategies to reconstruct the
      "tree of life", and have revealed the size of the ancestral plant genome,
      uncovered potential candidates for the ancestral flower, identified molecular
      living fossils, and linked the rate of neutral substitutions with species
      diversity. With an increased interest in DNA sequencing programmes in non-model
      organisms, the next decade will hopefully see these phylogenetic findings
      integrated into new genetic syntheses, from genomes to taxa.

PMID- 14642754
TI  - The DNA double helix fifty years on.
AB  - This year marks the 50th anniversary of the proposal of a double helical
      structure for DNA by James Watson and Francis Crick. The place of this proposal
      in the history and development of molecular biology is discussed. Several other
      discoveries that occurred in the middle of the twentieth century were perhaps
      equally important to our understanding of cellular processes; however, none of
      these captured the attention and imagination of the public to the same extent as
      the double helix. The existence of multiple forms of DNA and the uses of DNA in
      biological technologies is presented. DNA is also finding increasing use as a
      material due to its rather unusual structural and physical characteristics as
      well as its ready availability.

PMID- 14642755
TI  - Simulating cellular dynamics through a coupled transcription, translation,
      metabolic model.
AB  - In order to predict cell behavior in response to changes in its surroundings or
      to modifications of its genetic code, the dynamics of a cell are modeled using
      equations of metabolism, transport, transcription and translation implemented in
      the Karyote software. Our methodology accounts for the organelles of eukaryotes
      and the specialized zones in prokaryotes by dividing the volume of the cell into
      discrete compartments. Each compartment exchanges mass with others either through
      membrane transport or with a time delay effect associated with molecular
      migration. Metabolic and macromolecular reactions take place in user-specified
      compartments. Coupling among processes are accounted for and multiple scale
      techniques allow for the computation of processes that occur on a wide range of
      time scales. Our model is implemented to simulate the evolution of concentrations
      for a user-specifiable set of molecules and reactions that participate in
      cellular activity. The underlying equations integrate metabolic, transcription
      and translation reaction networks and provide a framework for simulating whole
      cells given a user-specified set of reactions. A rate equation formulation is
      used to simulate transcription from an input DNA sequence while the resulting
      mRNA is used via ribosome-mediated polymerization kinetics to accomplish
      translation. Feedback associated with the creation of species necessary for
      metabolism by the mRNA and protein synthesis modifies the rates of production of
      factors (e.g. nucleotides and amino acids) that affect the dynamics of
      transcription and translation. The concentrations of predicted proteins are
      compared with time series or steady state experiments. The expression and
      sequence of the predicted proteins are compared with experimental data via the
      construction of synthetic tryptic digests and associated mass spectra. We present
      the mathematical model showing the coupling of transcription, translation and
      metabolism in Karyote and illustrate some of its unique characteristics.

PMID- 14642756
TI  - Investigating protein domain combinations in complete proteomes.
AB  - Protein-related information is more accumulated rather than reduced to a
      synthetic view. Itemising properties of protein sequences is informative, so is
      the list of ingredients to do some cooking, but without a recipe, that is,
      quantification and chronology, understanding is incomplete. If the goal of
      accumulating information is to discover or reveal the function and related
      biochemical mechanisms, information has to be weighed and ordered. As a
      guideline, the weight of a piece of information should reflect how often it
      consistently occurs in various contexts. We propose a common sense approach to
      quantify and put data and information into perspective. Complete bacterial
      proteomes are individually mapped with the Pfam-A database of domains and protein
      family signatures in an attempt to assess the modularity of proteins at the level
      of a single proteome and the implications of a modular description of proteins
      for a functional interpretation. Poorly annotated proteins in the most documented
      bacteria (E. coli and B. subtilis) were considered in an attempt to formulate
      hypothesis on the basis of domain/module content.

PMID- 14642757
TI  - Detection of potential positive regulatory motifs of transcription in yeast
      introns by comparative analysis of oligonucleotide frequencies.
AB  - We conducted a comparative statistical analysis of tetra- through hexanucleotide
      frequencies in two sets of introns of yeast genes. The first set consisted of
      introns of genes that have transcription rates higher than 30 mRNAs/h while the
      second set contained introns of genes whose transcription rates were lower than
      or equal to 10 mRNAs/h. Some oligonucleotides whose occurrence frequencies in the
      first set of introns are significantly higher than those in the second set of
      introns were detected. The frequencies of occurrence of most of these detected
      oligonucleotides are also significantly higher than those in the exons flanking
      the introns of the first set. Interestingly some of these detected
      oligonucleotides are the same as well known "signature" sequences of
      transcriptional regulatory elements. This could imply the existence of potential
      positive regulatory motifs of transcription in yeast introns.

PMID- 14642758
TI  - Use of essential and molecular dynamics to study gammaB-crystallin unfolding
      after non-enzymic post-translational modifications.
AB  - Essential and Molecular Dynamics (ED/MD) have been used to model the
      conformational changes of a protein implicated in a conformational disease-
      cataract, the largest cause of blindness in the world-after non-enzymic post
      translational modification. Cyanate modification did not significantly alter
      flexibility, while the Schiff's base adduct produced a more flexible N-terminal
      domain, and intra-secondary structure regions, than either the cyanate adduct or
      the native structure. Glycation also increased linker flexibility and disrupted
      the charge network. A number of post-translational adducts showed structural
      disruption around Cys15 and increased linker flexibility; this may be important
      in subsequent protein aggregation. Our modelling results are in accord with
      experimental evidence, and show that ED/MD is a useful tool in modelling
      conformational changes in proteins implicated in disease processes.

PMID- 14642759
TI  - The PRALINE online server: optimising progressive multiple alignment on the web.
AB  - We introduce the online server for PRALINE
      (http://ibium.cs.vu.nl/programs/pralinewww/), an iterative versatile progressive
      multiple sequence alignment (MSA) tool. PRALINE provides various MSA optimisation
      strategies including weighted global and local profile pre-processing, secondary
      structure-guided alignment and a reliability measure for aligned individual
      residue positions. The latter can also be used to optimise the alignment when the
      profile pre-processing strategies are iterated. In addition, we have modelled the
      server output to enable comprehensive visualisation of the generated alignment
      and easy figure generation for publications. The alignment is represented in five
      default colour schemes based on: residue type, position conservation, position
      reliability, residue hydrophobicity and secondary structure; depending on the
      options set. We have also implemented a custom colour scheme that allows the user
      to select which colour will represent one or more amino acids in the alignment.
      The grouping of sequences, on which the alignment is based, can also be
      visualised as a dendrogram. The PRALINE algorithm is designed to work more as a
      toolkit for MSA rather than a one step process.

PMID- 14642760
TI  - DNA barcoding of parasites and invertebrate disease vectors: what you don't know
      can hurt you.

PMID- 14642761
TI  - Soil-transmitted helminth infections: updating the global picture.

PMID- 14642763
TI  - Did Herodotus describe the first airborne use of mosquito repellents?

PMID- 14642762
TI  - Topical application of DEET for schistosomiasis.

PMID- 14642764
TI  - Are hydrothermal vents oases for parasitic protists?

PMID- 14642765
TI  - Programmed cell death in parasitic protozoans that lack mitochondria.

PMID- 14642766
TI  - An enduring association? Microfilariae and immunosuppression [correction of
      immunosupression] in lymphatic filariasis.

PMID- 14642767
TI  - Costs of immune defense: an enigma wrapped in an environmental cloak?

PMID- 14642768
TI  - The 14-3-3 protein: a key molecule in parasites as in other organisms.

PMID- 14642769
TI  - Phylogenetics and sequence analysis--some problems for the unwary.

PMID- 14642770
TI  - Plasmodium vivax under the microscope: the Aotus model.

PMID- 14642771
TI  - Diacylglycerol pyrophosphate phosphatase in Saccharomyces cerevisiae.
AB  - Diacylglycerol pyrophosphate (DGPP) phosphatase in the yeast Saccharomyces
      cerevisiae is a Mg(2+)-independent and N-ethylmaleimide-insensitive 34-kDa
      vacuolar membrane-associated enzyme. It catalyzes the dephosphorylation of DGPP
      to form phosphatidate (PA) and then removes the phosphate from PA to form
      diacylglycerol (DAG). The enzyme is a member of the lipid phosphate phosphatase
      superfamily that contains a three-domain lipid phosphatase motif required for
      catalytic activity. Expression of the DPP1 gene, which encodes DGPP phosphatase,
      is induced by zinc depletion, by inositol supplementation, and when cells enter
      the stationary phase. Induction by zinc depletion is mediated by the
      transcription factor Zap1p, which binds to a zinc-responsive element in the DPP1
      promoter. Repression of DPP1 expression is mediated by the transcription factor
      Gis1p, which binds to three post-diauxic shift elements in the promoter.
      Regulation of DPP1 correlates with the expression of DGPP phosphatase activity
      and the cellular levels of DGPP and PA.

PMID- 14642772
TI  - Characterization and partial purification of protein fatty acyltransferase
      activity from rat liver.
AB  - The acylation of proteins through the addition of palmitate to cysteine residues
      is a common posttranslational modification for a variety of proteins, but the
      enzymology of this reversible modification has resisted elucidation. We developed
      a strategy to purify protein fatty acyltransferase (PAT) activity from rat livers
      that took advantage of recent knowledge on the cellular location and inhibition
      of PAT activity. We determined that three different thiolases have PAT activity
      in the presence of imidazole and therefore started the purification with a plasma
      membrane fraction to minimize the contamination with these enzymes. After
      detergent extraction of the plasma membrane fraction, the PAT activity was
      enriched about 90-fold by sequential chromatography including affinity
      chromatography to a cerulenin-based inhibitor of palmitoylation. The partially
      purified PAT activity (1) was lost with treatments to degrade or denature
      proteins, (2) could acylate tubulin, Galpha(i) and RGS16 and (3) showed a
      preference for palmitate and to a lesser degree other long-chain fatty acids.
      This purification procedure is a significant advance over previous efforts at PAT
      purification and a starting point for a proteomic approach for identification of
      mammalian PAT.

PMID- 14642773
TI  - Regulation of triacylglycerol hydrolase expression by dietary fatty acids and
      peroxisomal proliferator-activated receptors.
AB  - Triacylglycerol hydrolase (TGH) is an enzyme that catalyzes the lipolysis of
      intracellular stored triacylglycerol (TG). Peroxisomal proliferator-activated
      receptors (PPAR) regulate a multitude of genes involved in lipid homeostasis.
      Polyunsaturated fatty acids (PUFA) are PPAR ligands and fatty acids are produced
      via TGH activity, so we studied whether dietary fats and PPAR agonists could
      regulate TGH expression. In 3T3-L1 adipocytes, TGH expression was increased 10
      fold upon differentiation, compared to pre-adipocytes. 3T3-L1 cells incubated
      with a PPARgamma agonist during the differentiation process resulted in a 5-fold
      increase in TGH expression compared to control cells. Evidence for direct
      regulation of TGH expression by PPARgamma could not be demonstrated as TGH
      expression was not affected by a 24-h incubation of mature 3T3-L1 adipocytes with
      the PPARgamma agonist. Feeding mice diets enriched in fatty acids for 3 weeks did
      not affect hepatic TGH expression, though a 3-week diet enriched in fatty acids
      and cholesterol increased hepatic TGH expression 2-fold. Two weeks of clofibrate
      feeding did not significantly affect hepatic TGH expression or microsomal
      lipolytic activities in wild-type or PPARalpha-null mice, indicating that
      PPARalpha does not regulate hepatic TGH expression. Therefore, TGH expression
      does not appear to be directly regulated by PPARs or fatty acids in the liver or
      adipocytes.

PMID- 14642774
TI  - Divergent effects of eicosapentaenoic and docosahexaenoic acid ethyl esters, and
      fish oil on hepatic fatty acid oxidation in the rat.
AB  - The physiological activity of fish oil, and ethyl esters of eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) affecting hepatic fatty acid oxidation was
      compared in rats. Five groups of rats were fed various experimental diets for 15
      days. A group fed a diet containing 9.4% palm oil almost devoid of n-3 fatty
      acids served as a control. The test diets contained 4% n-3 fatty acids mainly as
      EPA and DHA in the form of triacylglycerol (9.4% fish oil) or ethyl esters (diets
      containing 4% EPA ethyl ester, 4% DHA ethyl ester, and 1% EPA plus 3% DHA ethyl
      esters). The lipid content of diets containing EPA and DHA ethyl esters was
      adjusted to 9.4% by adding palm oil. The fish oil diet and ethyl ester diets,
      compared to the control diet containing 9.4% palm oil, increased activity and
      mRNA levels of hepatic mitochondrial and peroxisomal fatty acid oxidation
      enzymes, though not 3-hydroxyacyl-CoA dehydrogenase activity. The extent of the
      increase was, however, much greater with the fish oil than with EPA and DHA ethyl
      esters. EPA and DHA ethyl esters, compared to the control diet, increased 3
      hydroxyacyl-CoA dehydrogenase activity, but fish oil strongly reduced it. It is
      apparent that EPA and DHA in the form of ethyl esters cannot mimic the
      physiological activity of fish oil at least in affecting hepatic fatty acid
      oxidation in rat.

PMID- 14642775
TI  - Induction of distinct sets of secretory phospholipase A(2) in rodents during
      inflammation.
AB  - Although the expression of the prototypic secretory phospholipase A(2) (sPLA(2)),
      group IIA (sPLA(2)-IIA), is known to be up-regulated during inflammation, it
      remains uncertain if other sPLA(2) enzymes display similar or distinct profiles
      of induction under pathological conditions. In this study, we investigated the
      expression of several sPLA(2)s in rodent inflammation models. In
      lipopolysaccharide (LPS)-treated mice, the expression of sPLA(2)-V, and to a
      lesser extent that of sPLA(2)-IID, -IIE, and -IIF, were increased, whereas that
      of sPLA(2)-X was rather constant, in distinct tissues. 12-O-Tetradecanoylphorbol
      13-acetate (TPA)-induced mouse ear edema, in which the expression of sPLA(2)-IID,
      -IIF and -V was increased, was significantly reduced by YM-26734, a competitive
      sPLA(2)-IIA inhibitor that turned out to inhibit sPLA(2)-IID, -IIE, -V and -X as
      well. In contrast, sPLA(2)-IIA was dominant in carageenin-induced pleurisy in
      rats, where the accumulation of exudate fluids and leukocytes was significantly
      ameliorated by YM-26734. These results indicate that distinct sPLA(2)s can
      participate in inflammatory diseases according to tissues, animal species, and
      types of inflammation.

PMID- 14642776
TI  - Copper-induced oxidative damage on astrocytes: protective effect exerted by human
      high density lipoproteins.
AB  - In the present study, we confirmed that copper ions induce oxidative damage in
      human astrocytes in culture, as demonstrated by the significant increase in the
      levels of hydroperoxides and in the fluorescence intensity of the fluorescent
      probe dichloro-dihydrofluorescein diacetate (H(2)DCFDA). The compositional
      changes were associated with a significant decrease in cell viability in
      astrocytes treated with 10 microM Cu(++) with respect to control cells.
      Astrocytes incubated with copper ions in the presence of high density
      lipoproteins (HDL) isolated from plasma of normolipemic subjects showed lower
      levels of hydroperoxides and a higher cell viability with respect to cells
      oxidized alone. Moreover, a significant decrease in the levels of hydroperoxides
      was observed in oxidized astrocytes treated with HDL. These results demonstrate
      that HDL exert a protective role against lipid peroxidation. The protective
      effect could be related to the ability of HDL to bind metal ions at the
      lipoprotein surface and/or to a stimulation of the efflux of lipid hydroperoxides
      from cell membranes as demonstrated in other cell types. Oxidative damage of
      astrocytes was induced at a copper concentration similar to that observed in
      cerebrospinal fluid (CSF) of patients affected by neurodegenerative diseases such
      as Alzheimer's (AD) and Parkinson's diseases (PD). Lipoprotein particles similar
      for density and chemical composition to plasma HDL were recently isolated in
      human CSF, therefore, the protective role exerted by HDL against Cu(++)-induced
      oxidative damage of astrocytes could be of physiological relevance.

PMID- 14642777
TI  - Role of Cl- currents in rat aortic smooth muscle activation by prostaglandin F2
      alpha.
AB  - The aim of this study was to determine the role of Cl(-) channel activation in
      prostaglandin F(2 alpha)-stimulated aortic contraction and in membrane
      depolarization during stimulation with prostaglandin F(2 alpha) in an aortic
      smooth muscle cell line (A7r5). The Cl(-) channel antagonists 5-nitro-2-(3
      phenylpropylamino) benzoic acid (NPPB), indanyloxyacetic acid-94 (IAA-94) and
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) were found to decrease
      (P<0.05) the maximum tension generated by rat thoracic aortic segments during
      stimulation with prostaglandin F(2 alpha) and to shift the concentration-response
      relationship to the right. In the presence of Nifedipine and Cesium, rat aorta
      derived A7r5 smooth muscle cells demonstrated outwardly rectifying voltage
      dependent currents that were inhibited by NPPB, IAA-94 and DIDS. Both inward and
      outward currents were enhanced (P<0.05) following addition of prostaglandin F(2
      alpha) (4 micromol/l, final concentration) to the bath solution and this increase
      was completely inhibited by NPPB. In the absence of Cesium, the addition of
      prostaglandin F(2 alpha) (4 micromol/l) to the extracellular bath solution either
      depolarized or hyperpolarized the cell membrane depending on the equilibrium
      potential for Cl(-) ions. Our results indicate that altered Cl(-) conductance is
      an important mechanism mediating membrane depolarization and contraction of
      aortic smooth muscle cells during stimulation with prostaglandin F(2 alpha).
      Given the significant role that prostaglandin F(2 alpha) and its biologically
      active isomers, the F(2) isoprostanes, play in the control of vascular tone
      during hypoxic and oxidative stress in the systemic circulation, alterations in
      Cl(-) channel function and expression may represent an important mechanism in the
      pathogenesis of abnormal blood flow regulation in disease states.

PMID- 14642778
TI  - Cyclopentyladenosine and some of its low-efficacy derivatives inhibit striatal
      synaptosomal release of acetylcholine to a similar degree.
AB  - The application of adenosine A(1) receptor agonists in regard to cerebral
      disorders is hampered by serious cardiovascular side effects. This problem might
      be circumvented by using low-efficacy agonists (partial agonists). The objective
      of the present study was to characterize the effects of the full agonist N(6)
      cyclopentyladenosine (CPA) and its low-efficacy derivatives 3'-deoxy-CPA (3
      DCPA), 8-propylamino-CPA (8-PCPA) and 8-butylamino-CPA (8-BCPA) on the 4
      aminopyridine (4AP)-evoked release of [3H]-acetylcholine in a rat striatal
      synaptosomal system. The reason for studying these partial agonists in particular
      was their established low cardiovascular side effect profile. CPA reached a
      concentration-dependent maximal inhibition of the evoked acetylcholine release of
      38+/-3%. 3-DCPA and 8-PCPA inhibited the acetylcholine release by 29+/-5% and
      38+/-3%, respectively. On the other hand, 8-BCPA only diminished the
      acetylcholine release by 19+/-3%. This inhibitory effect was reversible upon
      coadministration of the nonselective adenosine antagonist theophylline, but not
      by the selective adenosine A(2A) receptor antagonist 7-(2-phenylethyl)-5-amino-2
      (2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261). It is
      concluded that some partial adenosine A(1) receptor agonists behave as full
      agonists with respect to the inhibition of acetylcholine release, while lacking
      profound cardiovascular side effects. These preliminary results encourage further
      investigation of their tissue selectivity and therapeutic potential in vivo.

PMID- 14642779
TI  - Immunohistochemical detection of the calcitonin receptor-like receptor protein in
      the microvasculature of rat endothelium.
AB  - Calcitonin-gene-related peptide and adrenomedullin have similar and potent
      vascular effects, which appear to be mediated by the G protein-coupled calcitonin
      receptor-like (CRL) receptor. Using immunohistochemical and Western blot
      analyses, we have obtained novel evidence that CRL receptor is expressed in the
      rat vascular endothelium using an antibody to rat CRL receptor that we have
      raised and fully characterised. These results are an important basis for further
      studies aimed at determining the so far ill-defined functional significance of
      the extensive distribution of CRL receptor in the vascular endothelium.

PMID- 14642780
TI  - Lipopolysaccharide activates Akt in vascular smooth muscle cells resulting in
      induction of inducible nitric oxide synthase through nuclear factor-kappa B
      activation.
AB  - Bacterial lipopolysaccharide and other immunostimulants induce gene expression of
      an isoform of nitric oxide synthase (iNOS) in vascular smooth muscle cells. This
      process is dependent on nuclear factor-kappa B (NF-kappa B) activation. The aim
      of this study was to investigate whether the NF-kappa B and Akt signaling
      pathways converge to induce iNOS in lipopolysaccharide-stimulated vascular smooth
      muscle cells. Treatment of vascular smooth muscle cells with lipopolysaccharide
      plus interferon-gamma (LPS/IFN) caused activation of Akt and NF-kappa B. LPS/IFN
      caused activation of the iNOS promoter and transcription of iNOS mRNA/protein,
      resulting in NO production. A pharmacological inhibitor of the phosphoinositide 3
      kinase (PI3K)-Akt pathway, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
      (LY294002), inhibited phosphorylation of Akt and suppressed activation of NF
      kappa B by attenuating the phosphorylation and degradation of I kappa B. LY294002
      thereby inhibited LPS/IFN-induced iNOS expression and NO production. Another
      inhibitor of the PI3K-Akt pathway, wortmannin, also inhibited NO production in
      VSMC. LY294002 similarly inhibited interleukin-1 beta- or tumor necrosis factor
      alpha-induced NO production. The data indicate that lipopolysaccharide or
      cytokine stimulation of vascular smooth muscle cells leads to activation of the
      PI3K-Akt pathway, which then activates the NF-kappa B pathway. Thus, the PI3K-Akt
      pathway controls the expression of iNOS in lipopolysaccharide- and cytokine
      stimulated vascular smooth muscle cells.

PMID- 14642781
TI  - Modulation of mitogen-activated protein kinases by 6-nitro-7-hydroxycoumarin
      mediates apoptosis in renal carcinoma cells.
AB  - 6-Nitro-7-hydroxycoumarin has previously been shown to be a selective anti
      proliferative agent capable of activating p38, stress-activated protein kinase
      (SAPK) and mitogen-activated protein (MAP) kinase in the human renal cell
      carcinoma cell line, A-498. Here, the role of p38 MAP kinase was further
      investigated in relation to its participation in 6-nitro-7-hydroxycoumarin
      induced apoptosis. 6-Nitro-7-hydroxycoumarin was shown to alter cell cycle
      progression, leading to the appearance of a sub-G(1) peak, containing hypodiploid
      DNA, accompanied by increases in both poly(ADP-ribose)polymerase cleavage and
      decreased expression of cyclin D1. Drug treatment also lead to a rise in the
      expression in the cyclin-dependent kinase inhibitor, p21(WAF1/CIP1), and the
      appearance of inter-nucleosomal DNA cleavage and morphological changes,
      consistent with apoptotic cell death. Using a p38 MAP kinase inhibitor, SB203580,
      caused expression of p21(WAF1/CIP1) to be suppressed and both cleaved poly(ADP
      ribose)polymerase and the numbers of apoptotic cells were decreased. In summary,
      this study shows the participation of p38 MAP kinase in 6-nitro-7-hydroxycoumarin
      induced apoptosis of A-498 cells and suggests that targeting of p38 may represent
      a novel mechanism to inhibit renal cell carcinoma and that coumarin type drugs
      require further investigation as potential anticancer agents directed against
      renal cell carcinoma.

PMID- 14642782
TI  - Inhibiting caspase-8 after injury reduces hypoxic-ischemic brain injury in the
      newborn rat.
AB  - A broad spectrum caspase inhibitor reduces brain injury. Will a caspase-8
      inhibitor provide protection? Seven-day-old rat pups had the right carotid artery
      ligated, then were subjected to 2.5 h of 8% oxygen. Caspase-8 activity in the
      right cortex was measured enzymatically. Caspase-8 activity was increased at 12
      and 24 h after injury and IETD-CHO, (Ac-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu
      Leu-Ala-Pro-Ile-Glu-Thr-Asp-CHO, CHO is aldehyde) a cell permeable caspase-8
      inhibitor, given by i.c.v. injection after the hypoxic period eliminated this
      increase with significant effect at 15 and 50 microg/pup (1.7 micromol/kg).
      Thirty pups were randomly assigned to receive 50 microg/pup of IETD-CHO or
      vehicle i.c.v. immediately after the hypoxic period. The loss of brain weight in
      the right hemisphere 22 days after injury was 29+/-5% in the vehicle-treated
      animals and 12+/-5% in the IETD-CHO-treated animals (P<0.05). Inhibiting caspase
      8 activity after hypoxic-ischemic brain injury reduces brain injury.

PMID- 14642783
TI  - Activation of spinal orexin-1 receptor produces anti-allodynic effect in the rat
      carrageenan test.
AB  - Orexin-A and orexin-1 receptors are found in the dorsal root ganglion cells and
      the spinal dorsal horn and this suggests that orexin-A is involved in the spinal
      nociceptive transmission. The authors examined the effect of intrathecally
      administered orexin-A on the level of mechanical allodynia and thermal
      hyperalgesia induced by paw carrageenan injection in the rat. Intrathecal
      injection of 0.3 and 3 nmol of orexin-A suppressed the level of mechanical
      allodynia, but not that of thermal hyperalgesia, and the effect of orexin-A on
      mechanical allodynia was antagonized by the pretreatment of 1-(2-methylbenzoxazol
      6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride, SB-334867, a selective orexin
      1 receptor antagonist. These data suggest that the activation of spinal orexin-1
      receptor modulates the mechanical information transmission, but not thermal
      information transmission, in the spinal cord during carrageenan test.

PMID- 14642784
TI  - Low doses of nitroparacetamol or dexketoprofen trometamol enhance fentanyl
      antinociceptive activity.
AB  - We have reported that subeffective doses of the nonsteroidal anti-inflammatory
      drug (NSAID) dexketoprofen trometamol enhances micro-opioid receptor agonist
      fentanyl antinociception. The aim of this study was to assess if this effect can
      also be observed with other new cyclooxygenase-inhibitors such as
      nitroparacetamol, and in responses to high intensity electrical stimulation (wind
      up). Single motor units were recorded in male Wistar rats under alpha-chloralose
      anaesthesia. The antinociceptive effect of fentanyl was studied alone and in the
      presence of subeffective doses of dexketoprofen trometamol or nitroparacetamol.
      In responses to noxious mechanical stimulation, the potency of fentanyl was
      enhanced by more than threefold in the presence of the NSAIDs and no significant
      recovery was observed after 45 min. The opioid antagonist naloxone and the
      alpha(2)-adrenoceptor antagonist atipamezol did not reverse the effect. The
      enhancement of the effect of fentanyl in wind-up was lower though significant. We
      conclude that the co-administration of subeffective doses of new cyclooxygenase
      inhibitors and the micro-opioid receptor agonist fentanyl should be considered as
      a potential pain therapy.

PMID- 14642785
TI  - Aglycemia and ischemia depress spinal synaptic transmission via inhibitory
      systems involving NMDA receptors.
AB  - The effects of in vitro aglycemia (glucose-free) and ischemia (glucose-free and
      O(2)-free) were examined on the dorsal root-evoked ventral root spinal
      monosynaptic and polysynaptic reflexes in neonatal rat spinal cords. Aglycemia
      and ischemia depressed the reflexes in a time-dependent manner and abolished them
      by 35 min. The depression by ischemia began immediately while that by aglycemia
      began after 15 min. The NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric
      acid (APV), blocked the depression induced by aglycemia completely and that by
      ischemia partially. Strychnine (glycine(A) receptor antagonist) or bicuculline
      (GABA(A) receptor antagonist) blocked the aglycemia-induced depression of the
      reflexes. In the case of ischemia, strychnine but not bicuculline, blocked the
      depression partially. The results indicate that aglycemia and ischemia depress
      the synaptic transmission involving NMDA receptors. Aglycemia involves both gamma
      aminobutyric acid-ergic and glycinergic inhibitory transmission while ischemia
      involves other additional mechanisms.

PMID- 14642786
TI  - Effect of drugs active at adenosine receptors upon chronic stress-induced
      hyperalgesia in rats.
AB  - Hyperalgesia and altered activities of enzymes involved in nucleotide hydrolysis
      are observed after exposure to repeated restraint in rats. Here, we investigated
      the effect of an adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine (CPA,
      3.35 mg/kg, i.p.), adenosine A(1) receptor antagonist, 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX, 0.8 mg/kg, i.p.) as well the effect of an adenosine
      reuptake blocker, dipyridamole (5 mg/kg, i.p.), on nociception in chronically
      stressed and control rats. We repeatedly submitted rats to restraint for 40 days.
      Nociception was assessed with a tail-flick apparatus. The control group presented
      increased tail-flick latencies after administration of CPA and dipyridamole, but
      this effect was not observed in the stressed group. DPCPX by itself had no effect
      on nociception. The analgesic effect of CPA and dipyridamole observed in the
      control group was reverted by DPCPX. These results indicate the involvement of
      adenosine A(1) receptor in the antinociception observed in control animals and
      suggest that the pain signaling induced by chronic stress presents a different
      modulation involving the adenosinergic system.

PMID- 14642787
TI  - Morphine-induced decrease in mechanical allodynia is mediated by central, but not
      peripheral, opioid receptors in rats with inflammation.
AB  - The aim of this study was to investigate the mechanism underlying the effect of
      morphine on allodynia to complete Freund's adjuvant-induced inflammation in rats.
      Morphine (5 mg/kg, i.v.) markedly inhibited the mechanical stimulation-induced
      nociceptive reflex of the gastrocnemius muscle in the inflamed hind-limb, and the
      inhibition was blocked by naloxone (1 mg/kg). Teased fiber recordings were made
      from the tibial nerve innervating the inflamed hindpaw. Morphine at the same dose
      did not affect the spontaneous firing rate of A-type fibers, whereas it markedly
      decreased the spontaneous firing of C-type fibers. The present data suggested
      that the central, but not peripheral, plasticity triggered by inflammation
      induced facilitation of A(beta) fibers plays an important role in morphine
      induced alleviation of allodynia, whereas activation of opioid receptor
      expression on the peripheral terminals of C fibers may contribute to morphine
      induced alleviation of persistent pain of inflammation.

PMID- 14642788
TI  - In-depth characterization of CGRP receptors in human intracranial arteries.
AB  - The purpose of the present study was to characterize the effects of human (h)
      alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries
      from man and to investigate the presence of mRNA for the calcitonin receptor like
      receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3,
      in cerebral and middle meningeal arteries with and without endothelium, in
      microvessels and in the endothelial cells isolated from the human basilar artery.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of
      CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with
      and without endothelium as well as in microvessels and in the endothelial cells.
      Human and rat alpha- and beta-CGRP, amylin, adrenomedullin and [acetamidomethyl
      Cys(2,7)]human CGRP induced strong concentration-dependent relaxation of human
      cerebral and middle meningeal arteries. Removal of the endothelium neither
      changed the maximum relaxant response nor the pIC(50) values for alpha- and beta
      CGRP as compared to the responses in arteries with an intact endothelium. Human
      alpha-CGRP-(8-37) caused a shift of h alpha- and h beta-CGRP-induced relaxations
      in cerebral and middle meningeal arteries. Calculation of pK(B) values revealed
      that h alpha-CGRP-(8-37) could not significantly discriminate between relaxations
      induced by h alpha-CGRP (pK(B) around 6.8) and h beta-CGRP (pK(B) around 5.4).
      There was no significant difference in pK(B) value of h alpha-CGRP-(8-37) on h
      beta-CGRP-induced relaxation of human cerebral and middle meningeal arteries with
      and without endothelium. In conclusion, our molecular and pharmacological data
      support the existence of a single type of CGRP(1) receptors in the human
      intracranial circulation.

PMID- 14642789
TI  - Blockade of cell adhesion by a small molecule selectin antagonist attenuates
      myocardial ischemia/reperfusion injury.
AB  - Reperfusion injury is related closely to inflammatory reactions such as the
      activation and accumulation of neutrophils. We investigated the efficacy of a
      novel small molecule selectin antagonist (bimosiamose) in a rat model of
      transient left coronary artery occlusion (30 min) and reperfusion (24 h).
      Treatment with bimosiamose (25 mg/kg, intravenously at reperfusion) showed a
      significant reduction in infarction area/area at risk of approximately 41%
      compared to vehicle control (P=0.01) and preserved the left ventricular function.
      The accumulation of polymorphonuclear neutrophils at the site of area at risk was
      decreased significantly, accompanied by 78% reduction of the myeloperoxidase
      activity. Parallel-plate flow chamber analysis revealed that bimosiamose showed a
      significant inhibition in rolling (62%, P<0.001) and adhesion (38%, P<0.05) of HL
      60 cells to activated human umbilical vein endothelial cells compared with
      vehicle control. This study demonstrates for the first time that bimosiamose, a
      novel small molecule selectin antagonist, attenuates significantly
      ischemia/reperfusion injury.

PMID- 14642790
TI  - The phytoestrogen genistein enhances endothelium-independent relaxation in the
      porcine coronary artery.
AB  - Genistein, a phytoestrogen, possesses cardioprotective effects. Responses to
      genistein (0.1-100 microM) were assessed in 9,11-dideoxy-9 alpha, 11 alpha
      methanoepoxy prostaglandin F(2 alpha) (U46619)-contracted porcine coronary
      arterial rings, with significant relaxations at high concentrations. At
      concentrations with little relaxation, genistein (0.3-3 microM) did not affect
      relaxation produced by bradykinin and the calcium ionophore, A23187. In contrast,
      sodium nitroprusside- and cromakalim-induced relaxations were enhanced by
      genistein (3 microM). N(omega)-nitro-L-arginine methyl ester (L-NAME) (300
      microM) or Triton X-100 (0.5%) did not affect the enhancement of relaxation by
      genistein. The tyrosine kinase inhibitor, tyrphostin 23 (30 microM), had no
      effect on sodium nitroprusside-elicited relaxation. In summary, genistein relaxed
      porcine coronary artery at relatively high concentrations. At a physiologically
      relevant concentration (3 microM), it is devoid of significant vascular effect,
      but enhanced endothelium-independent relaxations. This effect of genistein does
      not involve the nitric oxide synthase (NOS) pathway and the endothelium, and is
      mediated through a mechanism different from tyrosine kinase inhibition.

PMID- 14642791
TI  - Direct effects of proton pump inhibitors on histamine release from rat
      enterochromaffin-like cells.
AB  - Enterochromaffin-like (ECL) cells play a central role in the regulation of
      gastric acid secretion. Previous studies have shown that proton pump inhibitors
      accelerate histamine release from ECL cells through the effects of gastrin.
      However, direct effects of proton pump inhibitors on ECL cells have not been
      demonstrated to date because the indirect effects of gastrin are difficult to
      suppress. We investigated the direct effects of proton pump inhibitors medication
      on ECL cells using an elutriation system. ECL cells were stimulated with gastrin
      or rabeprazole, and histamine release from ECL cells was measured. Rabeprazole
      increased histamine release through a pathway that differed from that of gastrin.
      The histamine increase was likely due to an acceleration of vesicular monoamine
      transporter 2 (VMAT2). Rabeprazole increased histamine release from ECL cells
      directly via VMAT2, but did not affect the total amount of histamine in the
      cells. The results suggest that patients receiving proton pump inhibitors for
      extended periods must be monitored extensively because gastric tumor
      proliferation may be promoted by increased histamine release from ECL cells.

PMID- 14642792
TI  - The role of renal sympathetic nervous system in the pathogenesis of ischemic
      acute renal failure.
AB  - We investigated the role of renal sympathetic nervous system in the progression
      of ischemia/reperfusion-induced acute renal failure in rats. Acute renal failure
      was induced by clamping the left renal artery and vein for 45 min followed by
      reperfusion, 2 weeks after the contralateral nephrectomy. Renal venous plasma
      norepinephrine concentrations markedly and significantly increased immediately
      after reperfusion, thereafter, the increased level declined but remained higher
      even at 24 h after reperfusion. Renal sympathetic nerve activity was
      significantly augmented during the renal ischemia. Renal denervation or the
      administration of pentolinium, a ganglion blocking agent, (5 mg/kg i.v.) at 5 min
      before ischemia attenuated the ischemia/reperfusion-induced renal dysfunction and
      histological damage, such as proteinaceous casts in tubuli and tubular necrosis.
      The elevation of renal venous norepinephrine levels after reperfusion was
      suppressed by renal denervation or pentolinium treatment. Thus, a surgical or
      pharmacological blockade of renal sympathetic nerve prevents the progression of
      ischemia/reperfusion-induced acute renal failure, thereby suggesting that renal
      sympathetic nervous system plays an important role in the development of the
      ischemic acute renal failure.

PMID- 14642793
TI  - Impaired gastric ulcer healing in diabetic rats: role of heat shock protein,
      growth factors, prostaglandins and proinflammatory cytokines.
AB  - Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little
      is known about the influence of diabetic conditions on the healing of gastric
      ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was
      used to induce diabetes mellitus in rats. Four weeks after streptozotocin
      injection, gastric ulcers were induced using the acetic acid method, and 10 days
      later, the healing rate and the gastric blood flow (GBF) were measured by
      planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major
      groups of rats with gastric ulcers were used: (1) vehicle (saline); (2)
      streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4)
      streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and
      release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non
      selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and
      rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay
      in ulcer healing ( approximately by 300%), accompanied by a decrease in the
      gastric mucosal blood flow was observed. The prolongation of the healing in
      diabetic animals was associated with an increase in gastric mucosal expression
      and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the
      vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion
      molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP
      70). Administration of insulin reversed the delay in ulcer healing and
      significantly decreased the expression of IL-1 beta and TNF-alpha, while
      producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an
      inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic
      rats, counteracted the increase in the area of gastric ulcer induced by
      streptozotocin, raised significantly gastric blood flow and suppressed the plasma
      TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the
      mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the
      rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats,
      and these changes were significantly augmented in diabetic animals. We conclude
      that: (1) Experimental diabetes dramatically impairs ulcer healing, depending
      upon the increased release of proinflammatory cytokines and the attenuation of
      angiogenesis that can limit the ulcer healing effects of locally produced HSP 70
      and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic
      rats, mainly due to the enhancement of angiogenesis and reduction in expression
      of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs
      such as aspirin prolonged ulcer healing under diabetic conditions due to
      suppression of endogenous prostaglandins and the fall in the microcirculation at
      the ulcer margin and these effects were mimicked by selective, so called "safe"
      COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important
      sources of prostaglandins that are essential in the ulcer healing in diabetes.

PMID- 14642794
TI  - Effect of 15-deoxy-delta 12,14-prostaglandin J2 on acute lung injury induced by
      lipopolysaccharide in mice.
AB  - 15-Deoxy-delta(12,14)-prostaglandin J(2) (15d-prostaglandin J(2)) has received
      attention for its anti-inflammatory properties. The present study investigated
      the efficacy of 15d-prostaglandin J(2) on acute lung injury induced by
      lipopolysaccharide in mice. ICR mice were administered with 15d-prostaglandin
      J(2) (10 microg/kg, 100 microg/kg, or 1 mg/kg) before intratracheal challenge
      with lipopolysaccharide (125 microg/kg). Treatment with 15d-prostaglandin J(2)
      did not ameliorate rather enhanced at a dose of 1 mg/kg the neutrophilic lung
      inflammation and pulmonary edema by lipopolysaccharide. The enhancement was
      concomitant with the increased lung expression of interleukin-1 beta, macrophage
      inflammatory protein-1 alpha, and macrophage chemoattractant protein-1. 15d
      prostaglandin J(2) increased the nuclear protein expression of peroxisome
      proliferator-activated receptor (PPAR)-gamma and inhibited the nuclear
      localization of nuclear factor-kappa B related to lipopolysaccharide. 15d
      prostaglandin J(2) increased the phosphorylation of c-Jun in the presence or
      absence of lipopolysaccharide. Our data suggest that 15d-prostaglandin J(2) may
      not be useful but potentially harmful for the therapeutic option of acute lung
      injury.

PMID- 14642795
TI  - Effects of cilomilast on dendritic cell function in contact sensitivity and
      dendritic cell migration through skin.
AB  - The phosphodiesterase 4 inhibitor cilomilast demonstrated strong inhibitory
      effects in a model of allergic contact dermatitis. In this study, we examined
      whether this inhibitory effect is at least partly due to modulation of dendritic
      cell function. Bone marrow-derived dendritic cells were pulsed with the
      sensitizer toluene-2,4-diisocyanate and administered subcutaneously to
      nonsensitized mice. Five days later, the mice were challenged with a low dose of
      toluene-2,4-diisocyanate onto the ears. In contrast to sham-treated mice, mice
      obtaining toluene-2,4-diisocyanate pulsed dendritic cells showed a significant
      increase in ear swelling. This swelling was not influenced when the dendritic
      cells were pre-incubated with cilomilast. When cilomilast was administered
      systemically simultaneously to the application of toluene-2,4-diisocyanate pulsed
      cells, there was an impaired allergic reaction provoked 5 days later.
      Additionally, a topical treatment with cilomilast resulted in a significant
      inhibition of skin dendritic cell migration. These results indicate that the
      antigen-presenting function of dendritic cells is not influenced by cilomilast
      but the dendritic cell T cell interaction and dendritic cell migration is
      modulated.

PMID- 14642796
TI  - The cyclo-oxygenase-2 inhibitor, rofecoxib, attenuates mucosal damage due to
      colitis induced by trinitrobenzene sulphonic acid in rats.
AB  - Cyclo-oxygenase-2 overexpression has been described in experimental colitis.
      However, there are controversial findings suggesting that its inhibition by
      selective cyclo-oxygenase-2 inhibitors not only may have a beneficial effect on
      experimental colitis, but also exacerbate the inflammation-associated colonic
      injury. Thus, the role of cyclo-oxygenase-2 inhibitors in the possible modulation
      of colon inflammation is controversial and remains uncertain. In this study, we
      evaluated the effects of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, on
      the extent and severity of ulcerative colitis caused by intracolonic
      administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats. The
      lesions and the inflammatory response were assessed by histology and measurement
      of myeloperoxidase activity. Interleukin-1 beta, prostaglandin E(2) and D(2)
      levels in colon mucosa and the immunohistochemical expression of the cyclo
      oxygenases-1 and -2 were also studied. Finally, we investigated the effects of
      rofecoxib on apoptosis of colonocytes by the appearance of DNA fragmentation.
      Inflammation following TNBS was characterized by increased colonic wall
      thickness, oedema, diffuse inflammatory cell infiltration in the mucosa, and
      necrosis. Increased myeloperoxidase activity, as an index of neutrophil
      infiltration in the mucosa, and interleukin-1 beta levels were also measured in
      the colon. Administration of rofecoxib significantly (P<0.05) reduced the colonic
      damage, the degree of neutrophil infiltration, and interleukin-1 beta levels. In
      addition, apoptosis was significantly increased in TNBS-treated rats, but not in
      rofecoxib plus TNBS-treated rats. We concluded that rofecoxib seems to have
      beneficial effects in TNBS-induced colitis by diminishing the initial stage of
      inflammation, probably by a mechanism related to inhibition of prostaglandin E(2)
      by the cyclo-oxygenase-2 pathway. The data suggest that cyclo-oxygenase-2
      selective inhibitors may have a therapeutic role in ulcerative colitis.

PMID- 14642797
TI  - Effect of inducible nitric oxide synthase inhibition by aminoguanidine on insulin
      like growth factor binding protein-3 in adjuvant-induced arthritic rats.
AB  - This study was designed to investigate whether nitric oxide (NO) mediates changes
      in insulin-like growth factor binding protein-3 (IGFBP-3) levels in rats with
      adjuvant-induced arthritis. Male Wistar rats were injected with complete Freund's
      adjuvant, and 20 days afterwards arthritic and control rats were injected daily
      with an inhibitor of inducible NO synthase (iNOS), aminoguanidine, or vehicle for
      8 days. The increase in serum levels of IGFBP-3 induced by arthritis was
      exacerbated by aminoguanidine treatment. Arthritis increased IGFBP-3 mRNA levels
      in the kidney but not in the liver. The inhibition of iNOS did not modify IGFBP-3
      gene expression in the kidney or in the liver in arthritic rats. However, the
      inhibitory effect of arthritis on the proteolysis of IGFBP-3 in serum was
      potentiated by aminoguanidine administration. These results indicate that
      arthritis increases serum IGFBP-3 by increasing its synthesis in the kidney and
      decreasing its proteolysis in serum and that these effects are not mediated by
      NO.

PMID- 14642798
TI  - Resiniferatoxin reversibly blocks adjuvant-induced thermal hyperalgesia in the
      rat.
AB  - The role of capsaicin-sensitive sensory afferents and mast cells in complete
      Freund's adjuvant (CFA)-induced thermal hyperalgesia and edema was investigated
      in rats. A single systemic injection of resiniferatoxin produced a reversible
      prevention of adjuvant-induced thermal hyperalgesia which lasted several days. In
      addition, resiniferatoxin markedly reduced the early edema. Chronic degranulation
      of mast cells with compound 48/80 also reduced the thermal hyperalgesia and
      edema, especially in the early phase of inflammation. Co-pretreatment with
      resiniferatoxin and compound 48/80 induced effects similar to those of
      resiniferatoxin alone. The data support the involvement of capsaicin-sensitive
      fibers in the adjuvant-induced inflammation.

PMID- 14642800
TI  - The impact of budesonide and other inhaled corticosteroid therapies in the
      management of asthma in children and adults.
AB  - BACKGROUND: Since the recognition that asthma is characterized by extensive
      inflammation of the airways, the use of inhaled corticosteroids (ICSs) as
      controller therapy has become central to successful disease management. As the
      prevalence of asthma increases worldwide, there is concern about increasing
      numbers of patients with untreated or undertreated asthma, which may lead to
      deterioration in disease control, with direct effects on morbidity and mortality
      rates. The costs attributed to asthma translate into a considerable economic
      burden, from the direct costs of medical treatment to the costs incurred through
      lost work or school days. International treatment guidelines currently recommend
      early intervention with ICS therapy to improve lung function and disease control.
      OBJECTIVE: This article reviews the role of therapy with ICSs, particularly
      budesonide, in improving the management of asthma in patients of all ages and in
      reducing the economic and social burdens of this disease. RESULTS: Randomized,
      controlled clinical studies confirm the efficacy of early intervention with ICSs
      in patients with mild persistent asthma. Regular use of an ICS can reduce the
      number of exacerbations and hospitalizations in patients of all ages and with all
      disease severities. CONCLUSIONS: Budesonide has a well-established efficacy and
      safety profile. Its once-daily dosing may contribute to improved adherence and
      cost-effectiveness.

PMID- 14642801
TI  - Expected characteristics of an ideal, all-purpose inhaled corticosteroid for the
      treatment of asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are well established as the mainstay
      of asthma therapy. A number of ICSs are now available, each with unique
      pharmacokinetic/pharmacodynamic profiles and physical characteristics. OBJECTIVE:
      This article reviews the key characteristics of an ideal ICS and uses examples of
      existing agents to indicate the extent to which therapies reach these goals.
      RESULTS: Improved therapeutic efficacy in an ICS may be offset by an increase in
      systemic effects. The ideal characteristics of an ICS include optimal clinical
      efficacy and no toxicity in combination with a convenient and easy-to-use inhaler
      device. To achieve this optimal profile, an ICS should have the following: a high
      affinity for and potency at the glucocorticoid receptor; prolonged retention in
      the lung; minimal or no oral bioavailability (ie, high first-pass inactivation);
      and rapid, complete systemic inactivation. The formulation and type of inhaler
      device are also important considerations: they should provide deposition in the
      lung in both large and small airways with no absorption effects outside the lung.
      ICSs should be evaluated for administration with several different delivery
      devices to ensure ease of use by patients of all ages with different asthma
      severities. An ICS that can be administered QD is also likely to improve patient
      adherence by simplifying the treatment regimen. CONCLUSION: An ideal ICS should
      have a large therapeutic margin, be used safely and effectively for long periods,
      be administered QD, be suitable for use in patients of all ages and asthma
      severities, and offer both control and prevention of asthma symptoms and
      exacerbations.

PMID- 14642802
TI  - The role of intracellular esterification in budesonide once-daily dosing and
      airway selectivity.
AB  - BACKGROUND: Since their introduction in the 1970s, inhaled corticosteroids (ICSs)
      have been used to control airway inflammation associated with asthma. Budesonide
      is one of the ICSs recommended as first-line therapy for mild to moderate
      persistent asthma. OBJECTIVE: This article describes the esterification of
      budesonide and how it results in prolonged, location-specific retention of drug
      in the airways, allowing once-daily dosing. RESULTS: Studies conducted over the
      past decade have shown that budesonide forms reversible fatty acid esters within
      the cells of airway tissue, resulting in the formation of an intracellular depot
      pool of inactive drug. As the intracellular concentration of free budesonide
      decreases, these budesonide esters are hydrolyzed back to their active state.
      This process increases budesonide's retention in the airways, prolongs its
      duration of action, and lowers the risk of systemic effects. CONCLUSIONS: By
      extending budesonide's local anti-inflammatory effect and increasing its airway
      selectivity, the esterification process appears to contribute to the drug's
      efficacy, particularly during once-daily administration. Reducing the number of
      required daily inhalations may increase patient compliance with asthma therapy,
      although this remains to be evaluated.

PMID- 14642803
TI  - Review of the unique properties of budesonide.
AB  - BACKGROUND: The aim of inhaled corticosteroid (ICS) therapy for asthma is to
      attain high therapeutic activity in the airways while keeping the risk of
      systemic adverse effects relatively low. However, the physicochemical and
      pharmacokinetic properties of various ICSs affect this ratio, thereby influencing
      their ability to fulfill the requirements of an ideal agent. OBJECTIVE: This
      article reviews the physical and pharmacokinetic properties of budesonide,
      outlining how they, safety data, and use of different inhalation devices enable
      budesonide to meet many of the clinical requirements of an ideal ICS for the
      treatment of asthma. RESULTS: ICS efficacy is influenced by lipophilicity, lung
      deposition, and retention in airway tissue, whereas the rate of elimination
      determines systemic activity. Budesonide is retained in the airways to a greater
      extent than other ICSs because of an esterification process that increases its
      lipophilicity. The prolonged retention of budesonide in the airways may
      contribute to its efficacy when administered QD. In addition to a pressurized
      metered-dose inhaler, budesonide is available as a dry-powder inhaler and in
      nebulized form, which can be used by asthma patients aged > or =6 months.
      CONCLUSIONS: When combined with delivery devices suitable for a spectrum of
      patient groups, the physical and pharmacokinetic properties of budesonide lend it
      many of the characteristics of an ideal ICS, including favorable efficacy and
      tolerability profiles.

PMID- 14642804
TI  - Therapeutic margin of budesonide in patients with mild to severe asthma.
AB  - BACKGROUND: The therapeutic margin of a drug is the difference between the
      optimal effective dose and the dose at which unacceptable adverse effects occur.
      This margin is particularly important in the case of therapies that are used long
      term for the control of chronic illnesses, such as inhaled corticosteroids (ICSs)
      in the treatment of asthma. Because data from controlled clinical studies
      indicate that the available ICSs have similar clinical efficacy, the safety
      profile is central to differentiating between them on the basis of their
      therapeutic margins. The main safety concern with long-term use and high doses of
      ICSs is systemic exposure that could result in such unwanted effects as cortisol
      suppression, a reduction in the final adult height of pediatric patients, and
      decreased bone mineral density. OBJECTIVE: This article reviews data from
      clinical trials, including long-term prospective studies, to compare the
      therapeutic margin of budesonide with those of other second-generation ICSs and
      to determine whether there are variations in the therapeutic margin with
      different delivery devices, severities of disease, or patient age. RESULTS: Based
      on the tolerability data for budesonide from short-term (6-12 wk) and long-term
      (1-9 y) studies in patients with mild to moderate persistent asthma, the dose
      response and dose-tolerability curves for budesonide delivered by dry-powder
      inhaler can be plotted in parallel. The margin between these curves-the
      therapeutic margin-is favorable and consistent in pediatric and adult patients
      and at all degrees of asthma severity. Fewer tolerability data are available for
      other ICSS. CONCLUSION: Whereas budesonide has clinical efficacy similar to that
      of other currently available ICSs, it has a good safety profile-and hence a
      favorable therapeutic margin-that is supported by long-term clinical data.
      Budesonides favorable therapeutic margin is probably a result of its
      pharmacokinetic and physical properties.

PMID- 14642805
TI  - Preclinical properties of budesonide: translation to the clinical setting.
AB  - BACKGROUND: Since the introduction of inhaled corticosteroids (ICSs) nearly 30
      years ago, the management of asthma has been transformed. It is now understood
      that asthma is primarily a disease of chronic inflammation, even in its milder
      forms, and that to delay treatment may lead to deterioration in lung function.
      International treatment guidelines for asthma recommend early intervention with a
      potent ICS, with the greatest benefit observed when treatment is started within 2
      years of the onset of symptoms. Each of the currently available ICSs has distinct
      physical and pharmacokinetic properties and is delivered via different devices.
      OBJECTIVE: This article brings together the findings and concepts presented in
      this supplement. It provides an overview of budesonide's predicted clinical
      efficacy and tolerability in patients with asthma based on its physical
      properties and pharmacokinetic and pharmacodynamic characteristics. CONCLUSIONS:
      Budesonide's physical properties and pharmacokinetic and pharmacodynamic profiles
      help predict its clinical efficacy and tolerability when used as early
      intervention in asthma. Study results indicate that lung deposition of budesonide
      is increased by delivery via dry-powder inhaler, enhancing the drug's efficacy in
      patients with newly diagnosed mild persistent asthma. The preclinical, clinical,
      and safety data support budesonide's predicted performance in the clinical
      setting.

PMID- 14642806
TI  - Calcium distributions in human hair by ToF-SIMS.
AB  - Calcium distributions on internal and external surfaces of longitudinally
      sectioned hairs were analysed with Time-of-Flight Secondary Ion Mass Spectrometry
      (ToF-SIMS). Externally, calcium deposits were observed at the cuticle scale
      edges. Internal sections showed that the bulk of calcium exists within or just
      inside the cuticle layer. The medulla may or may not be enriched and other
      localised concentrations exist in one of two forms; either associated with
      granular structures or the hair proteins. Calcium appears to show an affinity for
      proteins with low sulfur content.

PMID- 14642807
TI  - FT-IR study of heterologous protein expression in recombinant Escherichia coli
      strains.
AB  - Two recombinant Escherichia coli strains expressing different levels of an
      interferon fusion protein as inclusion bodies have been studied by Fourier
      transform infrared (FT-IR) microspectroscopy. A marker band at 1628 cm(-1)
      allowed monitoring of the protein expression by direct analysis of cell pellets
      in a rapid, non-invasive and quantitative way. The results demonstrate that FT-IR
      microspectroscopy is a technique of potential biotechnological interest for
      studying inclusion body formation.

PMID- 14642808
TI  - Diagnosis of enzyme inhibition based on the degree of inhibition.
AB  - In this work, a method for the diagnosis of kinetic inhibition, based on the
      dependence of the degree of inhibition (epsilon(i)) on the inhibitor
      concentration [I] and on the substrate concentration [S], is presented. Because
      the degree of inhibition is a ratio between rates, kinetic data are normalized by
      the introduction of an internal control-the rate of the uninhibited reaction.
      Therefore, the error associated with the kinetic measurements decreases and less
      experimental measurements are necessary to achieve the diagnosis. The process
      described, which uses graphical and/or non-linear fitting procedures, allows
      distinguishing between 20 different kinds of inhibition, including not only
      linear and hyperbolic, but also parabolic and rational 2,2 inhibitions. Rational
      2,2 indicates a new type of inhibition corresponding to an incomplete parabolic
      inhibition, i.e. mechanistically it corresponds to an inhibitor that binds to two
      inhibition sites producing enzymatic complexes that are still active. In spite of
      its comprehensiveness, the diagnosis process is greatly facilitated by the
      division of the diagnosis of the inhibition in a step-by-step procedure, where
      only two rival models are evaluated in each step. In the non-linear fittings, the
      choice between rival models uses a test based on information statistics theory,
      the Akaike information criterion test, in order to penalize complex models that
      tend to be favoured in fittings. Finally, equations that allow the determination
      of inhibition kinetic constants were also deduced. The formalism presented was
      tested by examining inhibition of acid phosphatase by phosphate (a linear
      competitive inhibitor).

PMID- 14642809
TI  - Beneficial properties of single-domain antibody fragments for application in
      immunoaffinity purification and immuno-perfusion chromatography.
AB  - We explored the possibility to apply single-domain antibodies from Camelidae for
      immunoaffinity purification of the ice structuring protein (ISP) from Lolium
      perenne, which modifies ice crystal growth and therefore has potential
      application in medicine, biotechnology, agriculture and (frozen) foods. Using
      phage display together with an appropriate selection method, a group of candidate
      fragments was isolated from a llama-derived immune library. Affinity
      chromatography using a purposely selected antibody coupled to a matrix yielded a
      completely pure and functional ISP. Due to the extreme refolding capabilities and
      physical stability of single-domain antibodies, the affinity matrix could be
      regenerated more than 2000 times without loss of capacity, while the fragment's
      monomeric nature permitted an efficient elution of antigen. The results of this
      study show that highly pure proteins can be recovered from biological material in
      a single-step process.

PMID- 14642810
TI  - Identification of Translin/Trax complex as a glucose response element binding
      protein in liver.
AB  - Previously, we found a novel protein factor in the livers of rats fed a high
      carbohydrate diet, which binds to the major late transcription factor (MLTF)-like
      site within the glucose response element (GRE) of the liver-type pyruvate kinase
      (L-PK) gene [J. Biol. Chem. 274 (1999) 1100]. This factor, termed glucose
      response element binding protein (GRBP), exists in both liver cytosol and
      nucleus. In order to identify GRBP, we purified to homogeneity cytosolic GRBP
      from rat liver extract and identified it as a Translin/Trax heteromeric complex.
      Based on partial amino acid sequences, we have cloned full-length rat cDNAs of
      both Translin and Trax. The nuclear and the cytosolic Translin/Trax complex were
      both large polymers of 240 and 420 kDa, respectively. The molar ratio of
      Translin/Trax in the polymers was 2:1 in the liver cytosols. The nuclear and
      cytosolic Translin/Trax complexes as well as expressed His-tagged Translin bound
      to double- and single-stranded MLTF sites of the GRE of L-PK gene more avidly
      than to single-stranded Bcl-CL1, which was initially thought to be specific for
      Translin. Our findings indicate that the Translin/Trax complex constitutes the
      previously described GRBP, and that this complex binds the GRE of the L-PK gene
      with high affinity. The precise physiologic role of GRBP, however, remains
      unclear.

PMID- 14642811
TI  - Expression and secretion of ficolin beta by porcine neutrophils.
AB  - Ficolins are collagenous lectins that bind N-acetylglucosamine (GlcNAc) as well
      as some bacterial surfaces, and may have opsonic and complement-activating
      functions. Ficolin alpha in porcine plasma binds Actinobacillus pleuropneumoniae
      serotype 5 (APP) in a GlcNAc-dependent manner. In the present study, we
      discovered that porcine neutrophils, but not platelets or mononuclear cells,
      contained a different ficolin that migrated as a 39-kDa band on SDS-PAGE and
      resembled a minor component of plasma ficolins that binds APP. However,
      neutrophil ficolins (pI range 6.4-7.4) were readily distinguished from plasma
      ficolin alpha (pI 5.2-5.8) by 2D PAGE. Neutrophil ficolin was consistent with
      ficolin beta by pI and peptide mass fingerprinting with matrix-assisted laser
      desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Porcine
      neutrophils expressed ficolin beta, but not ficolin alpha, as determined by RT
      PCR. Ficolin beta was present in the membrane and cytoplasmic fractions of
      nonactivated neutrophils, but the majority of ficolin beta was secreted upon
      activation with PMA. Ficolin alpha readily bound to intact APP, but ficolin beta
      did not under the same conditions. These studies demonstrate that neutrophils
      express ficolin beta and secrete it when activated; however, ficolin beta may
      have different binding functions than ficolin alpha.

PMID- 14642812
TI  - The biosynthesis of cysteine and homocysteine in Methanococcus jannaschii.
AB  - The pathway for the biosynthesis of cysteine and homocysteine in Methanococcus
      jannaschii has been examined using a gas chromatography-mass spectrometry (GC-MS)
      stable isotope dilution method to identify and quantitate the intermediates in
      the pathways. The first step in the pathway, and the one responsible for
      incorporation of sulfur into both cysteine and methionine, is the reaction
      between O-phosphohomoserine and a presently unidentified sulfur source present in
      cell extracts, to produce L-homocysteine. This sulfur source was shown not to be
      sulfide. The resulting L-homocysteine then reacts with O-phosphoserine to form L
      cystathionine, which is cleaved to L-cysteine. The pathway has elements of both
      the plant and mammalian pathways in that the sulfur is first incorporated into
      homocysteine using O-phosphohomoserine as the acceptor and the resulting
      homocysteine, via transsulfuration, supplies the sulfur for cysteine formation.
      The pathway leading to these two amino acids represents an example of metabolic
      thrift where the preexisting cellular metabolites O-phosphohomoserine and O
      phosphoserine are used as the ultimate source of the carbon framework for the
      biosynthesis of these amino acids. These findings explain the absence of
      identifiable genes in the genome of this organism for the biosynthesis of
      cysteine and homocysteine.

PMID- 14642813
TI  - Combination effects of complement regulatory proteins and anti-complement
      polymer.
AB  - We previously reported the development of a "cytomedicine" that consists of cells
      trapped in alginate-poly-L-lysine-alginate (APA) microcapsules and agarose
      microbeads. The functional cells that are entrapped in semipermeable polymer are
      completely isolated from cellular immune system. However, the ability of
      cytomedicine to isolate cells from the humoral immune system, which plays an
      essential role in xenograft rejection, is low. Therefore, the goal of the present
      study was to develop a novel cytomedicine that could protect the entrapped cells
      from injury of the complement system. We investigated the applicability of the
      complement regulatory protein (CRP), Crry, to cytomedicine. Crry-transfected
      cells entrapped within agarose microbeads resisted injury by complement to a
      degree, while entrapment of Crry transfected cells within agarose microbeads
      containing polyvinyl sulfate (PVS), a novel cytomedical device with anti
      complement activity, clearly protected against complement attack. These data
      indicate that the combination of a CRP and a cytomedical device with anti
      complement activity is a superior device for cytomedical therapy.

PMID- 14642814
TI  - Characterization of a trypsin-like serine protease of activated B cells mediating
      the cleavage of surface proteins.
AB  - Activated B cells may cleave their surface receptors due to the proteolytic
      activity on the cell membrane or in its vicinity. We attempted to isolate and
      characterize the protease(s) responsible for this cleavage. Zymograms prepared
      from the supernatant and the plasma membrane fraction of activated human B cells
      and BL41/95 cell line exhibited a 85-90 kDa doublet band with protease activity,
      while that of resting B cells did not. Soybean trypsin inhibitor (STI), Nalpha-p
      tosyl-L-lysine chloromethyl ketone (TLCK) and EDTA treatment abolished the
      activity of this protease. The excess of Zn(2+) ions in EDTA did not restore the
      enzymatic activity, while it was completely recovered in the presence of Ca(2+).
      We affinity-purified a 85-90 kDa protease from the supernatant of BL41/95 cells
      using STI coupled to Sepharose 4B beads, and measured its kinetic parameters. For
      the arginyl substrate K(M) was 358+/-59 microM and for the lysyl substrate 582+/
      103 microM. TLCK and benzamidine inhibited the protease at micromolar, while STI
      at nanomolar concentrations. Both the inhibition profile and the substrate
      specificity suggest that it is a trypsin-like serine protease. We assume that the
      85-90 kDa serine protease expressed on and secreted by activated B cells and
      BL41/95 cell line is responsible for the cleavage of various membrane proteins,
      including Fcgamma receptors; thus it may play a crucial role in regulating B
      cell's function.

PMID- 14642815
TI  - A cold-adapted endo-arabinanase from Penicillium chrysogenum.
AB  - Previously, three arabinan-degrading enzymes were isolated from Penicillium
      chrysogenum 31B. Here we describe another arabinan-degrading enzyme, termed Abnc,
      from the culture filtrate of the same organism. Analysis of the reaction products
      of debranched arabinan by high-performance anion-exchange chromatography (HPAEC)
      revealed that Abnc cleaved the substrate in an endo manner and that the final
      major product was arabinotriose. The molecular mass of Abnc was estimated to be
      35 kDa by SDS-PAGE. Enzyme activity of Abnc was highest at pH 6.0 to 7.0. The
      enzyme was stable up to 30 degrees C and showed optimum activity at 30 to 40
      degrees C. Compared with a mesophilic counterpart from Aspergillus niger, Abnc
      exhibited a lower thermal stability and optimum enzyme activity at lower
      temperatures. Production of Abnc in P. chrysogenum was found to be strongly
      induced by arabinose-containing polymers and required a longer culture time than
      did other arabinanase isozymes in this strain.

PMID- 14642816
TI  - Growth and membrane polarization in Pseudomonas aeruginosa UG2 grown in
      randomized microgravity in a high aspect ratio vessel.
AB  - Growth and membrane polarization of Pseudomonas aeruginosa UG2 cells grown under
      randomized microgravity (RMG) and 1xg were measured in a high aspect ratio vessel
      (HARV) and also in batch cultures mixed at 12 and 150 rpm in Erlenmeyer shake
      flasks. Membrane polarization was measured using the fluorescent probe, 1,6
      diphenyl-1,3,5-hexatriene (DPH). No differences were observed in the growth
      curves or membrane polarization values (about 0.300) under all three culture
      conditions. However, the net effect of RMG at the single cell level may be still
      unknown. It may be possible that RMG effects are species-dependent or bacterial
      cells with a small mass and volume may be near the threshold where RMG exerts a
      minimal effect.

PMID- 14642817
TI  - LC/ESI-MS analysis of two elastin cross-links, desmosine and isodesmosine, and
      their radiation-induced degradation products.
AB  - In this work, the effect of Fenton reaction on two elastin cross-linked amino
      acids, desmosine (DES) and isodesmosine (IDE), in the absence or presence of
      different wavelength radiations generated from artificial sources has been
      evaluated using LC/ESI-MS. Irradiation as well as incubation of DES or IDE
      solutions in the presence of Fe(2+) and H(2)O(2) resulted in products with m/z
      497.1 and 481.1 for [M+H](+). A strongly dose-dependent degradation of both amino
      acids was observed upon exposure to UVB at doses ranging from 0 to 3 J/cm(2) and
      a moderate dose-dependent degradation upon exposure to UVA at doses 10 times
      higher than that of UVB. A significant time-dependent degradation of DES and IDE
      was also observed upon exposure of these amino acids to a lamp emitting visible
      light similar to sunlight. Exposure of both amino acids to IR radiation (520 W)
      for 8 h did not cause significant degradation.

PMID- 14642818
TI  - Inhibition of human colon carcinoma cell growth by ammonia: a non-cytotoxic
      process associated with polyamine synthesis reduction.
AB  - Ammonia, produced by bacterial degradation of unabsorbed and endogenous
      nitrogenous compounds, is found to be present at millimolar concentrations in the
      colon lumen. From in vivo animal experiments, this metabolite has been shown to
      alter colonic epithelial cell morphology and to increase compensatory cell
      proliferation when present in excess. In this in vitro study, using the human
      colon adenocarcinoma HT-29 Glc(-/+) cell line treated with increasing doses of
      NH(4)Cl, we found that 20 mM NH(4)Cl, a concentration close to that found in the
      large intestine lumen, was able to increase the volume of vacuolar lysosomes and
      to repress HT-29 Glc(-/+) cell proliferation. This growth-inhibitory effect was
      not correlated with decrease of cell viability, with modification of cell
      differentiation and change of the cell distribution in the different cell cycle
      phases, thus indicating a proportional slowdown in all cell cycle phases. In
      contrast to what is found in healthy colonocytes, ammonia was not metabolized by
      HT-29 cells into carbamoyl-phosphate (carbamoyl-P) and citrulline, indicating
      that ammonia was likely acting on cells by itself. This agent was shown to
      markedly reduce cellular ornithine decarboxylase (ODC) activity resulting in a
      threefold decrease in the capacity of HT-29 cells to synthetize polyamines, these
      latter metabolites being strictly necessary for cell growth. The unexpected
      finding that ammonia is acting as an antimitotic agent against tumoral HT-29
      colonic cells may be related to the inability of these cells to metabolize this
      compound.

PMID- 14642819
TI  - Cyclin-dependent kinase 11(p110) activity in the absence of CK2.
AB  - Cyclin-dependent kinase (CDK)11(p110), formerly known as PITSLRE, is a
      serine/threonine kinase whose catalytic activity has been associated with
      transcription and RNA processing. To further evaluate the regulation of
      CDK11(p110) catalytic activity, interacting proteins were identified by liquid
      chromatography and tandem mass spectrometry (LC-MS/MS). Following the
      immunoprecipitation of CDK11(p110) from COS-7 cells, the serine/threonine kinase
      CK2 was identified by LC-MS/MS. These results were extended through the
      observation that CDK11(p110) serves as a substrate for CK2 and the identification
      of a phosphorylation site on CDK11(p110) at Ser227 by LC-MS/MS. To obtain
      CDK11(p110) devoid of CK2, CDK11(p110) was expressed in High Five insect cells
      and secreted into the media due to the presence of a honeybee melittin signal
      sequence encoded at the amino-terminus of CDK11(p110). Recombinant CDK11(p110)
      was purified from the media and phosphorylation of histone H1 subsequently
      demonstrated. After demonstrating retention of CDK11(p110) kinase activity, it
      was evaluated for activity on the carboxyl-terminal domain (CTD) of the largest
      subunit of RNA polymerase II (RNAP II), but only CK2 was found to phosphorylate
      the CTD.

PMID- 14642820
TI  - Nucleotide and deduced amino acid sequences of a high-molecular-mass subtilisin
      from an alkaliphilic Bacillus isolate.
AB  - A high-molecular-mass subtilisin was found in culture broth of the alkaliphilic
      Bacillus sp. strain KSM-KP43. The gene encoding the enzyme (FT protease) was
      determined using a mixed primer designed from the N-terminal amino acid (aa)
      sequence of the purified enzyme. The determined nucleotide sequence of the gene
      consisted of a 2427-bp open reading frame (ORF) that encoded a putative prepro
      peptide (152 aa) and a mature enzyme (656 aa; 68,506 Da). The deduced aa of the
      mature enzyme revealed a moderate homology to a subtilisin-type proteinase from
      Bacillus halodurans and a minor extracellular protease, Vpr, from Bacillus
      subtilis with 64% and 57% identity, respectively. The molecular mass of the
      purified recombinant FT protease was approximately 72 kDa as judged by both SDS
      polyacrylamide gel electrophoresis (PAGE) and gel filtration. FT protease showed
      maximal activity toward glutaryl-Ala-Ala-Pro-Leu-p-nitroanilide at pH 10.5 and at
      45 degrees C. The enzyme was rapidly inactivated by incubation over 45 degrees C
      for 15 min at both pH 7 and 10. Calcium ions were slightly protective for
      thermoinactivation of the enzyme.

PMID- 14642821
TI  - Photosensitized inactivation of T7 phage as surrogate of non-enveloped DNA
      viruses: efficiency and mechanism of action.
AB  - We investigated the efficiency and the mechanism of action of a tetraphenyl
      porphyrin derivative in its photoreaction with T7 phage as surrogate of non
      enveloped DNA viruses. TPFP was able to sensitize the photoinactivation of T7
      phage in spite of the lack of its binding to the nucleoprotein complex. The
      efficiency of TPFP photosensitization was limited by the aggregation and by the
      photobleaching of porphyrin molecules. Addition of sodium azide or 1,3-dimethyl-2
      thiourea (DMTU) to the reaction mixture moderated T7 inactivation, however,
      neither of them inhibited T7 inactivation completely. This result suggests that
      both Type I and Type II reaction play a role in the virus inactivation. Optical
      melting studies revealed structural changes in the protein part but not in the
      DNA of the photochemically treated nucleoprotein complex. Polymerase chain
      reaction (PCR) also failed to demonstrate any DNA damage. Circular dichroism (CD)
      spectra of photosensitized nucleoprotein complex indicated changes in the
      secondary structure of both the DNA and proteins. We suggest that damages in the
      protein capsid and/or loosening of protein-DNA interaction can be responsible for
      the photodynamic inactivation of T7 phage. The alterations in DNA secondary
      structure might be the result of photochemical damage in phage capsid proteins.

PMID- 14642823
TI  - Detachment and sonoporation of adherent HeLa-cells by shock wave-induced
      cavitation.
AB  - The interaction of lithotripter-generated shock waves with adherent cells is
      investigated using high-speed optical techniques. We show that shock waves
      permeabilize adherent cells in vitro through the action of cavitation bubbles.
      The bubbles are formed in the trailing tensile pulse of a lithotripter-generated
      shock wave where the pressure drops below the vapor pressure. Upon collapse of
      cavitation bubbles, a strong flow field is generated which accounts for two
      effects: first, detachment of cells from the substrate; and second, the temporary
      opening of cell membranes followed by molecular uptake, a process called
      sonoporation. Comparison of observed cell detachment with results from a
      theoretical model considering peeling cell detachment by a wall jet-induced shear
      stress shows reasonable agreement.

PMID- 14642822
TI  - Antibacterial activity and mechanism of action of tick defensin against Gram
      positive bacteria.
AB  - Defensins are a major group of antimicrobial peptides and are found widely in
      vertebrates, invertebrates and plants. Invertebrate defensins have been
      identified from insects, scorpions, mussels and ticks. In this study, chemically
      synthesized tick defensin was used to further investigate the activity spectrum
      and mode of action of natural tick defensin. Synthetic tick defensin showed
      antibacterial activity against many Gram-positive bacteria but not Gram-negative
      bacteria and low hemolytic activity, characteristic of invertebrate defensins.
      Furthermore, bactericidal activity against pathogenic Gram-positive bacteria
      including Bacillus cereus, Enterococcus faecalis and methicillin-resistant
      Staphylococcus aureus was observed. However, more than 30 min was necessary for
      tick defensin to completely kill bacteria. The interaction of tick defensin with
      the bacterial cytoplasmic membrane and its ability to disrupt the membrane
      potential was analyzed. Tick defensin was able to disrupt the membrane potential
      over a period of 30-60 min consistent with its relatively slow killing.
      Transmission electron microscopy of Micrococcus luteus treated with tick defensin
      showed lysis of the cytoplasmic membrane and leakage of cellular cytoplasmic
      contents. These findings suggest that the primary mechanism of action of tick
      defensin is bacterial cytoplasmic membrane lysis. In addition, incomplete cell
      division with multiple cross-wall formation was occasionally seen in tick
      defensin-treated bacteria showing pleiotropic secondary effects of tick defensin.

PMID- 14642824
TI  - "In vitro" effect of cumene hydroperoxide on hepatic elongation factor-2 and its
      protection by melatonin.
AB  - We have examined by immunoblotting the effect of three oxidant compounds on the
      level of hepatic elongation factor-2 (eEF-2). Rat liver homogenates were exposed
      to cumene hydroperoxide (CH), 2-2'-azobis (2-aminopropane) dihydrochloride (AAPH)
      and H(2)O(2). Only CH treatment produced the disappearance of eEF-2, probably due
      to a phenomena of peptide bond cleavage. The direct implication of free radical
      species in this process is evident because of the fact that the inclusion of a
      free radical scavenger such as melatonin prevented the eEF-2 depletion. The
      results also suggest that the disappearance of eEF-2 induced by CH can be linked
      to a lipid peroxidant process, which could account for the decline of protein
      synthesis in aging and other circumstances where lipid peroxidation is high.

PMID- 14642825
TI  - Serotonin 2C receptors within the basolateral amygdala induce acute fear-like
      responses in an open-field environment.
AB  - Several studies indicate a role for the serotonin 2 subfamily (5-HT(2A), 5
      HT(2B), 5-HT(2C)) in mediation of fear and anxiety responses. The current study
      began to examine the effects of stimulating 5-HT(2C) receptors within the
      basolateral (BLA) or central nucleus of the amygdala (CeA) on acute fear-like
      responses in rats. Bilateral intra-BLA infusions of mCPP (3-3000 pmol), a mixed 5
      HT(2) agonist, produced ultrasonic vocalization and reduced exploratory behavior
      while increasing the latency to investigate a novel object. These responses were
      attenuated by SB-242084, a 5-HT(2C)-specific antagonist. Furthermore, a selective
      5-HT(2C) agonist, IL-639, produced a similar repertoire of behavioral effects
      with the exception of effects on time spent in the center of an open-field arena.
      Finally, infusions of mCPP into the CeA produced no anxiogenic behaviors
      suggesting that 5-HT(2C) receptors primarily within the BLA are responsible for
      many of the acute fear-like responses reported here. To characterize further the
      neural circuits associated with 5-HT(2C)-mediated fear responses, we assessed c
      fos mRNA expression after intra-BLA infusions of mCPP, IL-639 or their vehicles.
      Whereas the overall regional pattern of c-fos mRNA induction for the two
      compounds was distinct, c-fos activation was confined primarily to limbic nuclei
      with the medial prefrontal cortex as a common regional target of each drug. These
      results suggest that activation of 5-HT(2C) receptors within the BLA influences
      the activity of limbic circuits involved in the expression of acute innate fear
      responses.

PMID- 14642826
TI  - 17beta-Estradiol extends ischemic thresholds and exerts neuroprotective effects
      in cerebral subcortex against transient focal cerebral ischemia in rats.
AB  - Neuroprotective effects of estrogens are demonstrated consistently in the
      cerebral cortex, but not in subcortical areas. In the present study, transient
      middle cerebral artery occlusions (MCAO) were induced for various duration, and
      protective effects of estrogen treatment on the cerebral cortex and subcortex
      were evaluated. MCAO was induced for 30, 40 or 60 min in ovariectomized rats.
      Animals were treated with 17beta-estradiol (E2) or vehicle (OVX) 2 h before MCAO
      and sacrificed 24 h after the indicated duration of MCAO. Ischemic lesion was
      evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin
      staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) staining. E2 treatment reduced the magnitude and delayed the appearance
      of the total ischemic lesion area and largely prevented TUNEL staining in the
      cortex. In the subcortex, E2 treatment prevented the ischemic lesion in the 30
      min group, reduced lesion area in the 40-min group, but had no effect on ischemic
      lesion area in the 60-min group. E2 treatment significantly decreased apoptotic
      cell number in the subcortical area at 30 and 40 min, but not at 60 min of MCAO.
      This study demonstrated that estrogen treatment can protect the cerebral
      subcortex in a severity-dependent manner, suggesting that the lack of protective
      effects of estrogen treatment in the subcortex is not due to the lack of estrogen
      receptors. Further, this study indicates that estrogens could be used as a
      neuroprotectant to prolong the therapeutic window of thrombolysis and prolong the
      time of cerebral circulation intervention for neurosurgical procedure.

PMID- 14642827
TI  - Neurosphere and neurosphere-forming cells: morphological and ultrastructural
      characterization.
AB  - Despite recent advances in our understanding of neural stem cell (NSC) biology,
      the free-floating structures generated by these cells in vitro, the
      "neurospheres", have not been fully characterized. To fill this gap, we examined
      neurospheres and neurosphere-derived NSCs by confocal microscopy, electron
      microscopy (EM) and cytofluorimetry. Here, we show that neurospheres and
      neurosphere-forming cells are morphologically and functionally heterogeneous.
      Confocal microscopy reveals differences in cell size, viability, cytoplasmic
      content and in the presence and distribution of active mitochondria. By electron
      microscopy, neurospheres appear as complex structures in which biological events
      such as mitosis, apoptosis and even phagocytosis are influenced by NSCs
      localization within the architecture of the neurosphere. NSCs derived from
      neurospheres are not synchronized and are represented in all phases of the cell
      cycle. Cytofluorimetric studies demonstrate NSCs' heterogeneity in cell size by
      forward scatter (FSC) analysis, and in cytoplasmic granularity by side scatter
      (SSC) profiling. These findings may contribute to our understanding of the
      morphogenesis of the neurospheres, particularly as this process relates to the
      high environmental adaptability of the NSCs and the reported existence of
      different subpopulations of neural stem cells.

PMID- 14642828
TI  - Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin.
AB  - The integration of 'long-term' adiposity signaling with the 'short-term' meal
      related signal cholecystokinin (CCK) is proposed to involve descending
      hypothalamic projections to areas of the caudal brainstem (CBS) that regulate the
      amount of food consumed during a single meal. One such projection extends from
      cell bodies in the hypothalamic paraventricular nucleus (PVN) to the nucleus
      tractus solitarius (NTS), where cells that respond to peripheral CCK are
      concentrated. Candidate neuronal cell types that may comprise this PVN-NTS
      projection includes those expressing corticotropin-releasing hormone (CRH) or
      oxytocin. We therefore sought to determine whether oxytocin or CRH axons are
      preferentially located in close anatomical proximity to neurons of the NTS that
      are activated by peripheral administration of CCK, as determined by
      immunocytochemical staining for Fos protein. Rats received injections of either
      an anorexic dose of CCK (8 nmol/kg, i.p.) or vehicle and were perfused 2 h later
      with 4% paraformaldehyde. Immunocytochemistry was performed on cryostat sections
      (14 microm) of caudal brainstem, using a polyclonal antibody to Fos protein and
      either a monoclonal antibody to oxytocin or a polyclonal antibody to CRH. As
      expected, CCK administration significantly increased the numbers of Fos-positive
      neurons by 489% (p<0.01) and 400% (p<0.01), respectively, in the medial and
      gelatinosus subdivisions of the NTS. These same regions received dense oxytocin
      axon innervation, whereas CRH immunoreactivity was not as prevalent in these
      areas. In areas outside the NTS, such as the dorsal motor nucleus of the vagus
      (DMV), Fos activation was absent despite a dense oxytocin and CRH innervation. To
      investigate whether CCK-induced reductions of food intake require intact oxytocin
      signaling, we performed a separate study in which CCK injection was preceded by
      injection into the fourth ventricle of an oxytocin receptor antagonist
      [d(CH(2))(5), Tyr (Me)(2), Orn(8)]-vasotocin (OVT). This study showed CCK was 23%
      and 22% less effective at inhibiting food intake at 30 min (p<0.05) and 1 h
      (p<0.05) food intake, respectively, in the presence of OVT. Taken together, the
      data indicate that oxytocin axons within the descending pathway from the PVN to
      the NTS are anatomically positioned to interact with NTS neurons that respond to
      vagally mediated peripheral CCK signals such as those that occur following
      ingestion of a meal. These findings support the hypothesis that oxytocin exerts a
      tonic stimulatory effect on the response of key neurons within the NTS to CCK and
      further reduce meal size.

PMID- 14642829
TI  - The neuronal nitric oxide synthase inhibitor, TRIM, as a neuroprotective agent:
      effects in models of cerebral ischaemia using histological and magnetic resonance
      imaging techniques.
AB  - Most neuroprotective compounds that appear promising in the pre-clinical phase of
      testing are subsequently dismissed as relatively ineffective when entered into
      large-scale clinical trials. Many pre-clinical studies of potential
      neuroprotective candidates evaluate efficacy in only one or possibly two
      different models of ischaemia. In this study we examined the effects of 1,2
      trifluoromethylphenyl imidazole (TRIM), a novel neuronal nitric oxide synthase
      (nNOS) inhibitor, in three models of cerebral ischaemia (global gerbil, global
      rat and focal rat). In addition, to follow the progression of the pathology, we
      also compared traditional histology methods with more advanced magnetic resonance
      imaging (MRI) as endpoint measures for neurological damage and neuroprotection.
      TRIM (50 mg/kg i.p.) prevented ischaemia-induced hippocampal damage following
      global ischaemia in gerbils when administered before or immediately post
      occlusion, but failed to protect when administration was delayed until 30 min
      post-occlusion. Further studies indicated that the compound (administered at 50
      mg/kg, i.p., immediately after occlusion) also protected in a rat four-vessel
      occlusion (4-VO) model using both histological and diffusion-weighted (DW)
      imaging techniques. In a final study, TRIM (50 mg/kg i.p. 30 min after occlusion)
      provided a significant reduction in infarct volume at 4 and 24 h as measured
      using diffusion-weighted (DW) and proton density (PD)-weighted magnetic resonance
      imaging (MRI). This was confirmed using histological techniques. These studies
      confirm that nNOS inhibitors may have utility in stroke and provide evidence that
      combined magnetic resonance and histological methods can provide a powerful
      method of assessing neuronal damage in rodent models of cerebral ischaemia.

PMID- 14642830
TI  - Pharmacokinetics of L-dopa in plasma and extracellular fluid of striatum in
      common marmosets.
AB  - L-3, 4-Dihydroxyphenylalanine (L-dopa) has been widely used for the treatment of
      Parkinson's disease (PD), but its pharmacokinetics in the striatum have hardly
      been investigated, especially in primates. In this study, we examined the
      concentration of L-dopa in plasma and in the extracellular fluid (ECF) of the
      striatum in common marmosets using microdialysis and high-performance liquid
      chromatography (HPLC) with electrochemical detection. With a clinically
      therapeutic dosage of L-dopa/benserazide (20/5 mg/kg, p.o.), the t(max) of L-dopa
      was 30 min in plasma and 60-90 min in ECF of striatum. Mean C(max) was 20.3
      microM in plasma and 442.9 nM in ECF of striatum, which is about 2.2% of that in
      plasma. The L-dopa concentration in ECF is much lower than those previously
      applied during in vivo studies for L-dopa toxicity.

PMID- 14642831
TI  - Areal and synaptic interconnectivity of prelimbic (area 32), infralimbic (area
      25) and insular cortices in the rat.
AB  - This study investigated the interconnectivity of areas in the medial prefrontal
      and insular cortices in the rat. The areas studied were the prelimbic (PL, area
      32) and infralimbic (IL, area 25) cortices and the dorsal anterior agranular
      insular (AId) and regions of posterior insular cortex (PI-comprising the
      agranular, dysgranular and granular fields). Following injections of the
      anterograde tracer biotinylated dextran amine (BDA) into layers 2-5 of each area,
      labelled axonal varicosities were found ipsilaterally in the other cortical
      areas. The most prominently labelled pathways were PL-->AId, AId-->PL, IL-
      >AId/PI, and PI-->IL. Qualitative and quantitative examinations of the laminar
      distribution of labelled axonal varicosities in the terminal fields indicated the
      existence of topographically organised 'feed-forward' (insular to PL/IL) and
      'feed-back' (PL/IL to insular) pathways. The identity of the post-synaptic
      targets innervated by the PL/IL to AId pathways were investigated
      ultrastructurally. An analysis of 250 anterogradely labelled synaptic boutons
      (taken from layers 2/3) indicated that spine heads (presumed to originate from
      pyramidal cells) were the principal (88-93%) targets; all identified synaptic
      junctions were asymmetric. The results define an interconnected network of
      reciprocal pathways between cortical areas processing general and specific
      'viscerosensory' information (AId and PI) and medial areas involved in cognitive
      (PL) and visceromotor (IL) functions. The data provide important aspects of the
      cortical circuitry underlying the integration of cognitive and emotional
      processing mechanisms, not only in rats, but also in primates.

PMID- 14642832
TI  - Galectin-1 is involved in the potentiation of neuropathic pain in the dorsal
      horn.
AB  - Galectin-1 is one of the endogenous-galactoside-binding lectins, suggested to be
      involved in a variety of functions, such as neurite outgrowth, synaptic
      connectivity, cell proliferation and apoptosis. This protein is expressed in the
      dorsal root ganglion (DRG) and the spinal cord in the developing and adult rats,
      especially intensely in small DRG neurons. In the present study, we examined
      whether galectin-1 is colocalized with TrkA or c-Ret mRNA in small DRG neurons
      and the effect of axotomy on the expression of galectin-1 in the spinal cord.
      About 20% of the DRG neurons showed intense galectin-1-immunoreactivity (IR). Of
      the intensely galectin-1-IR DRG neurons, 93.9% displayed c-Ret mRNA positive
      signals. On the other hand, only 6.8% displayed TrkA mRNA positive signals.
      Galectin-1-IR was increased in the dorsal horn at 1 to 2 weeks after axotomy.
      Intrathecal administration of anti-recombinant human galectin-1 antibody (anti
      rhGAL-1 Ab) partially but significantly attenuated the upregulation of substance
      P receptor (SPR) in the spinal dorsal horn and the mechanical hypersensitivity
      induced by the peripheral nerve injury. These data suggest that endogenous
      galectin-1 may potentiate neuropathic pain after the peripheral nerve injury at
      least partly by increasing SPR in the dorsal horn.

PMID- 14642833
TI  - Fetal brain regional responses to cerebral hypoperfusion: modulation by estrogen.
AB  - We have previously demonstrated that cerebral hypoperfusion stimulates several
      physiological and molecular responses which are components of homeostatic
      reflexes. Physiological increases in fetal plasma estradiol concentration
      modulate fetal brain responsiveness to hypotension. In the present study, we
      tested the effect of cerebral hypoperfusion and/or estradiol on the expression of
      Fos, the protein product of the gene c-fos in late-gestation fetal sheep. We
      hypothesized that estrogen and cerebral hypoperfusion alone would augment Fos
      abundance in various brain regions, including the hypothalamus and brainstem, and
      that estrogen would augment or otherwise modify the Fos response to cerebral
      hypoperfusion. Singleton or twin fetuses of time-dated pregnant ewes were
      chronically catheterized and fitted with an extravascular balloon occluder around
      the brachiocephalic artery using aseptic techniques. In one-half of the fetuses,
      we implanted a pellet subcutaneously which released estradiol at a rate of 5 mg
      in 21 days. Fetuses were studied at least 5 days after surgery (124-128 days'
      gestation, term is approximately 147 days). One-half of the fetuses were
      subjected to a 10-min period of brachiocephalic occlusion (BCO). One hour after
      the start of the experiment, the ewe and fetus were euthanized and the fetal
      brain was rapidly recovered, dissected, and frozen in a polypropylene tube in an
      acetone/dry ice bath. Brain tissue was homogenized in a boiling lysis buffer, and
      protein concentrations measured using the Bradford method. Extracted proteins
      were electrophoresed on 7.5% polyacrylamide gels, transferred to nitrocellulose
      membranes, and probed for Fos. In most brain regions, estradiol or BCO altered
      the expression of Fos. Analyzed by two-way analysis of variance, there was a
      statistically significant (p<0.05) interaction between estradiol and BCO in
      brainstem, cerebellum, and hippocampus, nearly significant in hypothalamus
      (p=0.07) and not statistically significant in cerebral cortex. In these regions
      with statistically significant interactions, the expression of Fos in response to
      the combined treatment of estradiol and BCO was less than the sum of responses to
      either treatment alone. We conclude that estradiol has a potent action on the
      fetal brain which is identifiable in the brainstem, cerebellum, and hippocampus
      and that it modulates the Fos response to cerebral hypoperfusion. The measurement
      of regional Fos responses using Western blot reveals a negative interaction
      between estrogen and BCO which might result from alterations in cerebral blood
      flow or metabolism.

PMID- 14642834
TI  - Muscimol prevents NMDA antagonist neurotoxicity by activating GABAA receptors in
      several brain regions.
AB  - N-Methyl-D-aspartate (NMDA) glutamate receptor antagonists are being developed as
      therapeutic agents for several clinical conditions. However, the ability of these
      agents to produce neurotoxicity and psychosis can compromise their clinical
      usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state may play a
      role in neurodegenerative and psychotic disorders. A better understanding of the
      mechanism underlying these adverse effects should allow for the safer use of
      these agents and might clarify mechanisms underlying certain clinical disorders.
      NRHypo neurotoxicity is mediated by a complex disinhibition mechanism in which
      NMDA antagonists abolish GABAergic inhibition, resulting in the simultaneous
      excessive release of acetylcholine and glutamate onto the vulnerable
      retrosplenial cortex (RSC) neurons. Systemically administered GABAergic agents
      are potent protectors against NRHypo neurotoxicity. To determine where in brain
      GABAergic agents could be acting to protect against NRHypo neurotoxicity, we
      injected the GABAergic agonist, muscimol, into different brain regions of rats
      treated systemically with a neurotoxic dose of the potent NMDA antagonist, MK
      801. We report that muscimol injections into the anterior thalamus or diagonal
      band of Broca provide substantial protection, suggesting that disinhibition of
      neurons in these regions underlies NRHypo neurotoxicity. Muscimol injections into
      the RSC also provide substantial protection possibly by directly inhibiting the
      vulnerable RSC neuron. Injections of muscimol into other areas known to project
      to the RSC (ventral orbital cortex, anterior cingulate cortex and subiculum)
      provide only minimal protection. We conclude that GABAergic agents prevent NRHypo
      neurotoxicity mainly by activating GABA receptors in the anterior thalamus,
      diagonal band of Broca and RSC.

PMID- 14642835
TI  - Development of a postnatal 3-day-old rat model of mild hypoxic-ischemic brain
      injury.
AB  - Improvements in both obstetric and paediatric care have been responsible for a
      continuing reduction in mortality in extremely premature infants. However, higher
      survival rates have been at the expense of more long-term neurological damage.
      Various animal models have been developed to study the effect of hypoxic-ischemic
      insults on the brain. However, established models like the postnatal day 7 rat
      model represent damage found in term infants rather than in preterm infants of 24
      28 weeks' gestation, and produce a severe form of injury resulting in high
      mortality rates. In this study we developed a reliable model of minor hypoxic
      ischemic brain injury in postnatal day 3 rats. At this maturity, the pattern of
      damage represents that expected in a preterm infant suffering a non-lethal
      perinatal insult. We found that minor changes in duration of insult and both
      temperature and humidity produced wide fluctuations in the degree of injury
      observed. By maintaining strict control over experimental conditions including
      duration of insult, temperature and humidity, we produced a reliable model of
      minor injury primarily affecting all five areas of the cerebral cortex, and also
      the thalamus (area 7) and basal ganglia (area 8). Differences were significant
      compared to normal controls and sham-operated animals (p<0.05). These areas
      represent the primary motor, insular, visual and temporal cortices. The overall
      mortality rate in this study was 12.3%.

PMID- 14642836
TI  - Hydroxyapatite-coated tendon chitosan tubes with adsorbed laminin peptides
      facilitate nerve regeneration in vivo.
AB  - On the inner surface of tendon chitosan tubes having a triangular shape and a
      hydroxyapatite coating (t-chitosan/HAp tube), laminin-1 and laminin peptides
      (YIGSR, IKVAV) have been adsorbed in order to develop nerve growth conduits. The
      mechanical property, biocompatibility and efficacy of these tubes for nerve
      regeneration were examined. Step-1: bridge grafting (15 mm) into the sciatic
      nerve of Sprague-Dawley (SD) rats was carried out using either t-chitosan or t
      chitosan/HAp tubes having either a circular or triangular cross section (N=12 in
      each group). Specimens were taken after 2-, 4-, 6- and 8-week post-implantation
      (N=3 in each group) for histology determinations. Step-2: t-chitosan/HAp tubes
      having a triangular cross section with adsorbed laminin-1, CDPGYIGSR or
      CSRARKQAASIKVAVSAD, as well as control tubes without pre-adsorption were used for
      implantation (N=18 in each group). Isografting was also carried out (N=6).
      Histological evaluation was carried out similarly as in Step-1. Furthermore,
      evoked muscle and sensory nerve action potentials were recorded, and the
      percentage of myelinated axon area measured at 10 mm distance of the distal
      anastomosed site in the experimental, control and isograft groups after 12 weeks
      (N=6 in each group). The results of histological findings, as well as mechanical
      properties, suggest that a triangular tube shape with a HAp coating benefits
      nerve regeneration. The effect of laminin peptides (YIGSR, followed by IKVAV) to
      enhance the growth of regenerating axons has been found comparable with intact
      laminin-1. Although histological regeneration in both the YIGSR- and laminin-1
      treated t-chitosan/HAp tubes matches the isografts, the functional recovery is
      however delayed.

PMID- 14642837
TI  - NMDA-evoked consumption and recovery of mitochondrially targeted aequorin
      suggests increased Ca2+ uptake by a subset of mitochondria in hippocampal
      neurons.
AB  - Activation of NMDA receptors produces large increases in cytosolic Ca(2+) that
      are taken up into mitochondria. We used recombinant aequorin targeted to
      mitochondria to report changes in matrix Ca(2+) in rat hippocampal neurons in
      culture. Upon binding Ca(2+), aequorin emits a photon in a one-shot reaction that
      consumes the indicator. Here we show that stimulation with NMDA produced a
      mitochondrial Ca(2+) response that rapidly inactivated. However, following a 30
      min recovery period the response was restored, suggesting the presence of a pool
      of indicator that was not exposed to high Ca(2+) during the initial stimulus. We
      speculate that aequorin distant from the Ca(2+) source was protected from
      microdomains of high Ca(2+) near the plasmalemma and that this aequorin moved,
      either by movement of individual mitochondria or via the mitochondrial tubular
      network, to replenish consumed indicator during the recovery time. A large Ca(2+)
      increase in a subset of mitochondria could produce local changes in energy
      metabolism, regional Ca(2+) buffering, and foci that initiate neurotoxic
      processes.

PMID- 14642838
TI  - Heat shock protects PC12 cells against MPP+ toxicity.
AB  - A mild heat shock preconditioning has been shown to induce thermotolerance and
      protection against a number of cytotoxic agents that may induce cell death by
      either apoptosis or necrosis. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      is a neurotoxin that selectively targets dopaminergic cells of the substantia
      nigra and, as such, it is often used to induce neuronal cell death in models of
      Parkinson's disease. PC12 cells were heat-shocked for 1 h at 41.5 degrees C. This
      led to a rapid induction of Hsp25 and Hsp70. Levels of these proteins remained
      elevated for at least 24 h post heat shock. Treatment of PC12 cells with 1-methyl
      4-phenylpyridinium (MPP(+)), the active metabolite of MPTP, resulted in cell
      death. Morphological analysis and the lack of caspase activity suggested that
      cell death was by necrosis. Heat shocking the cells 6 h prior to addition of
      MPP(+) significantly inhibited the induction of cell death by MPP(+). These
      results indicated that heat shock is protective against MPP(+) neurotoxicity in
      PC12 cells.

PMID- 14642839
TI  - Mitochondrial hyperpolarization after transient oxygen-glucose deprivation and
      subsequent apoptosis in cultured rat hippocampal neurons.
AB  - Mitochondrial membrane potential (MMP) regulates the production of high-energy
      phosphate and apoptotic cascade, both occurring after ischemic impact. The timed
      profile of MMP differing from grading ischemic impact has to be determined.
      Primary rat hippocampal cultures were exposed to oxygen-glucose deprivation (OGD)
      for 30, 60, and 90 min and then were reoxygenated. MMP was expressed as a voltage
      dependent dye, JC-1 fluorescence, under confocal microscopy. Cell viability was
      assessed by calcein AM and ethidium homodimer, each at 3 hours and 24 hours after
      30, 60, and 90 min of OGD. The appearance of apoptosis was also evaluated by the
      TUNEL method at 24 hours. Hyperpolarization of MMP (2.31+/-0.94 normalized JC-1
      fluorescence ratio between red and green) was observed during reoxygenation after
      30 min OGD, while 60 min OGD induced depolarization (0.66+/-0.22, Valinomycin
      (potassium ionophore)-induced depolarization: 0.53+/-0.19). The fluorescence of
      mitochondria became weak after 90 min OGD. Most of the neurons were shrunken
      after 90 min and neurons were TUNEL-positive 24 hours after 30 min OGD, although
      most neurons were viable at 3 hours. A longer period of OGD induced necrosis, and
      most neurons remained viable after only 3 hours. Our data present that the short
      (30 min) OGD induced hyperpolarization of MMP during reoxygenation, while a
      longer OGD (60 or 90 min) induced depolarization and acute necrosis. Neurons were
      still viable even during hyperpolarization of mitochondria, but this
      hyperpolarization appears to be linked to subsequent apoptotic change.

PMID- 14642840
TI  - Coeruleotrigeminal inhibition of nociceptive processing in the rat trigeminal
      subnucleus caudalis.
AB  - It has been accepted that the descending system from the nucleus locus coeruleus
      (LC)/nucleus subcoeruleus (SC) plays a significant role in spinal nociceptive
      processing. The present study was designed to examine modulation of nociceptive
      processing in the caudal part of the trigeminal sensory nuclear complex, the
      trigeminal subnucleus caudalis which is generally considered to be involved in
      the relay of oral-facial nociceptive information. Experiments were performed on
      anesthetized Sprague-Dawley rats. The site of LC/SC stimulation was confirmed by
      histology using potassium ferrocyanide to produce a Prussian blue reaction
      product marking the iron deposited from the stimulating electrode tip. Only data
      from rats which had electrode placements in the LC/SC were used. Electrical
      stimulation was delivered at a stimulus intensity below 100 microA in the present
      study. Stimulation at sites inside the LC/SC produced a reduction of both
      spontaneous activity and responses of subnucleus caudalis neurons to somatic
      input, especially nociceptive input. Increasing stimulation frequency in the
      LC/SC resulted in an increase in inhibitory effects on nociceptive responses of
      subnucleus caudalis neurons. At three of nine sites outside the LC/SC, electrical
      stimulation was effective on descending inhibition. A significant difference in
      the inhibitory effects was observed when the inhibitory effects were compared
      between sites of stimulation inside the LC/SC and three effective sites of
      stimulation outside the LC/SC. These findings suggest that nociceptive processing
      in the subnucleus caudalis is under the control of the descending modulation
      system from the LC/SC. To understand the effects of repetitive stimulation with
      high frequency on fine unmyelinated LC/SC fibers, the existence of recurrent
      collateral excitation in the LC/SC may be considered.

PMID- 14642841
TI  - Choline acetyltransferase-immunoreactive neurons in the retina of adult and
      developing lampreys.
AB  - The presence of choline acetyltransferase-immunoreactive (ChATir) amacrine cells
      is reported for the first time in the retinas of three species of lamprey
      (Lampetra fluviatilis, Ichthyomyzon unicuspis, and Petromyzon marinus). In the
      three species, the ChATir cells were mainly distributed in the inner plexiform
      layer (IPL), which in lampreys extends from the inner nuclear layer (INL) to the
      inner limiting membrane. These cells had a bipolar, triangular or stellate
      appearance, and gave rise to processes coursing in the inner plexiform layer. In
      transforming lampreys, ChATir processes formed two asymmetrical inner and outer
      subplexuses in the inner plexiform layer, which is reminiscent of the
      distribution of processes of ChATir cells in the On and Off sublaminae reported
      in jawed vertebrates. The larval retina lacked ChAT immunoreactivity, and ChATir
      cells and processes appeared at early metamorphosis throughout the retina,
      exhibiting in late transforming stages an organization similar to that of adults.
      This first report of ChATir cells in the lamprey retina indicates that the
      appearance of cholinergic circuits in the retina of vertebrates occurred before
      the divergence of the agnathan and gnathostome lines.

PMID- 14642842
TI  - Sleep alterations in an experimental orofacial pain model in rats.
AB  - This study sought to assess sleep patterns in rats injected with Freund's
      adjuvant (FA) in the temporomandibular joint (TMJ) as a potential experimental
      orofacial pain model. Pain response to indomethacin was also assessed. Rats were
      implanted with electrodes to record electrocorticogram and eletromyogram signals.
      After a baseline (B) recording, they were injected with Freund's adjuvant
      (orofacial pain group, n=8) or saline (sham group, n=8) in the temporomandibular
      joint, and their sleep was monitored over two 12-h light periods. In the second
      phase of the study, after injecting Freund's adjuvant, indomethacin was
      administered (1 mg/kg p.o.) at 12- intervals, and sleep patterns were recorded
      for two additional light periods. The orofacial pain group showed a reduction in
      sleep efficiency during the two light periods compared with the baseline
      recording and with the sham group (p<0.001). Increases in sleep and paradoxical
      sleep (PS) latencies of approximately 200% and 420%, respectively, were observed,
      as well as an increase in the number of awakenings during both periods (p<0.001).
      Treatment with indomethacin increased sleep efficiency (p<0.001) and paradoxical
      sleep time (p<0.001). The number of awakenings (p<0.001) and sleep (p<0.001) and
      paradoxical sleep latencies (p<0.001) were reduced reestablishing the normal
      sleep pattern. The results showed the reliability and usefulness of the
      temporomandibular joint pain model to characterize sleep disturbances related to
      pain and its response to indomethacin.

PMID- 14642843
TI  - D-chiro-Inositol enhances effects of hypothalamic toxin gold-thioglucose.
AB  - D-chiro-Inositol (DCI) enhances reproductive function in insulin-resistant women
      with polycystic ovarian disease and enhances the effects of insulin in the
      periphery, suggesting that this compound may act in part by sensitizing the
      hypothalamus to effects of insulin. Effects of gold-thioglucose (GTG) to produce
      hypothalamic lesions and subsequent obesity are insulin-dependent, suggesting
      that responses to GTG may be a marker of hypothalamic sensitivity to insulin. To
      assess these hypotheses, the present study assessed if DCI would enhance the
      ability of a subthreshhold dose of GTG to produce hypothalamic lesions and
      subsequent obesity. At the subthreshhold dose used (0.4 mg/kg i.p.), injection of
      GTG produced no subsequent effect on body weight compared to saline; similarly,
      at the dose of DCI used (10 mg/kg/day in drinking water), DCI produced no effect
      on body weight. In contrast, when given to mice exposed to DCI, this dose of GTG
      produced significant increase in body weight and evidence of an enhanced medial
      arcuate hypothalamic lesion.

PMID- 14642844
TI  - Moxonidine and central alpha2 adrenergic receptors in sodium intake.
AB  - Central injections of the alpha(2) adrenergic/imidazoline receptor agonist
      moxonidine inhibit water and NaCl intake in rats. In the present study, we
      investigated the possible involvement of central alpha(2) adrenergic receptors on
      the inhibitory effect of moxonidine in 0.3 M NaCl intake induced by 24 h sodium
      depletion. Male Holtzman rats with stainless-steel cannulas implanted into the
      lateral ventricle (LV) were used. Sodium depletion was produced by the treatment
      with the diuretic furosemide (20 mg/kg of body weight) injected subcutaneously
      +24 h of sodium-deficient diet. Intracerebroventricular (icv) injections of
      moxonidine (20 nmol/1 microl) reduced sodium depletion-induced 0.3 M NaCl intake
      (6.6+/-1.9 ml/120 min vs. vehicle: 12.7+/-1.7 ml/120 min). Pre-treatment with the
      alpha(2) adrenoreceptor antagonists RX 821002 (80 nmol/1 microl), SK&F 86466 (640
      nmol/1 microl) and yohimbine (320 nmol/3 microl) injected icv abolished the
      inhibitory effect of icv moxonidine on sodium depletion-induced 0.3 M NaCl intake
      (13.3+/-1.4, 15.7+/-1.7 and 11.8+/-2.2 ml/120 min, respectively). The results
      show that the activation of alpha(2) adrenoreceptors is essential for the
      inhibitory effect of central moxonidine on sodium depletion-induced NaCl intake.

PMID- 14642845
TI  - The hypothalamic paraventricular nucleus and carotid receptors modulate
      hyperglycemia induced by hemorrhage.
AB  - The aim of this study was to assess the role of cholinergic transmission in the
      paraventricular nucleus of the hypothalamus (PVN) and carotid body receptors in
      mediating a rise in plasma glucose levels in response to hemorrhagic hypotension
      in rats. Methylatropine (1x10(-9) mol) or 0.15 M NaCl (0.2 microl) was injected
      into the PVN of Wistar rats weighing 250-300 g bearing a chronic jugular catheter
      for blood sampling and hemorrhage (1.2 ml/100 g/2 min). Polyethylene cannulae (PE
      10) were inserted into the left femoral artery for cardiovascular monitoring. In
      the other experimental protocol, hemorrhage was performed on rats submitted to
      bilateral carotid receptor denervation (H-CD). The results show that the
      hyperglycemic response to hemorrhage was decreased by either methylatropine (H
      MA) treatment or bilateral carotid receptor denervation (10.3+/-0.4 mM, control,
      n=15 vs. 7.7+/-0.2 mM, H-MA, n=12, and 7.6+/-0.3 mM, H-CD, n=5, p<0.01).
      Furthermore, methylatropine did not affect the recovery of blood pressure after
      hemorrhage-induced hypotension, suggesting that the metabolic and pressor
      adjustments have different efferent pathways. Our data demonstrate that
      cholinergic input from the PVN and carotid receptors (chemo- and/or
      baroreceptors) might participate in the same neural pathway activated by
      hemorrhage-induced hypotension that produces hyperglycemia.

PMID- 14642846
TI  - Copper binding to PrPC may inhibit prion disease propagation.
AB  - Although it has been well established that PrP(C), the normal isoform of PrP(Sc),
      is a copper-binding protein, the role of this metal in the function of PrP(C) as
      well as in prion disease pathology remains unclear. Here, we show that when
      scrapie-infected neuroblastoma cells were cultured in the presence of copper, the
      accumulation of PrP(Sc) in these cells was markedly reduced. In addition, our
      results indicate that when normal neuroblastoma cells were cultured in the
      presence of copper ions, they could no longer bind and internalize PrP(Sc). In
      another set of experiments, copper was added to the drinking water of normal and
      scrapie-infected hamsters. Our results show that administration of copper to
      normal hamsters induced cerebellar PrP(C) accumulation. Most important, a
      significant delay in prion disease onset was observed when scrapie-infected
      hamsters were treated with copper. As shown before for neuroblastoma cells, also
      in vivo most of the copper-induced accumulation of PrP(C) was intracellular. We
      hypothesized that PrP(C) internalization by copper may hinder PrP(Sc) interaction
      with this molecule, and thereby affect prion disease propagation.

PMID- 14642847
TI  - Differential effects of glucose on dehydroascorbic acid transport and
      intracellular ascorbate accumulation in astrocytes and skeletal myocytes.
AB  - Skeletal muscle and brain are major sites of glucose transport and ascorbate
      (vitamin C) storage. Ascorbate is oxidized to dehydroascorbic acid (DHAA) when
      used as an enzyme cofactor or free radical scavenger. We evaluated the hypothesis
      that glucose regulates DHAA uptake and reduction to ascorbate (i.e., recycling)
      by skeletal muscle cells and cerebral astrocytes. DHAA uptake was inhibited
      partially by glucose added simultaneously with DHAA. Comparison of wild type L6
      skeletal muscle cells with an L6-derived cell line (D23) deficient in
      facilitative hexose transporter isoform 3 (GLUT3), indicated that both GLUT3 and
      facilitative hexose transporter isoform 1 (GLUT1) mediate DHAA uptake.
      Preincubation of muscle cells with glucose inhibited the rates of glucose and
      DHAA uptake, and decreased the intracellular concentration of ascorbate derived
      from recycling of DHAA. In contrast, glucose preincubation did not depress GLUT1
      protein and activity levels or DHAA recycling in astrocytes. These results
      establish that glucose downregulates subsequent recycling of DHAA by skeletal
      muscle cells but not astrocytes.

PMID- 14642848
TI  - Peripheral nerve regeneration in RGD peptide incorporated collagen tubes.
AB  - This paper describes the regeneration of lesioned sciatic nerve with collagen
      tubes incorporated with RGD cell-adhesive peptide. Collagen implants of 14 mm
      were grafted to bridge a gap length of 10 mm nerve defect in a rat model. The
      regenerated tissues were analyzed histomorphologically. The number of myelinated
      axons in the regenerated mid-graft of the RGD peptide incorporated groups was
      statistically significant (p<0.05) than control collagen tube and autograft
      control after 30 days postoperatively. After 90 days of implantation, the mean
      counts were still statistically significant in the case of RGD peptide group than
      control collagen and autograft groups. Immunofluorescence studies demonstrated
      the staining of S100 proteins in the peripherally located cells indicating the
      proliferation of Schwann cells in the early days of regeneration. The staining
      pattern of integrin-alphaV was observed mostly in the perineurial regions in
      close proximity to the RGD peptide incorporated collagen tubes. Other studies
      like sciatic functional index, conduction velocity at 90 days postoperatively
      suggest complete regeneration of lesioned nerves with RGD incorporated collagen
      implants.

PMID- 14642849
TI  - Expression of IKKalpha mRNA in the suprachiasmatic nucleus and circadian rhythms
      of mice lacking IKKalpha.
AB  - In our previous study, quantitative trait locus (QTL) analysis using mice with
      abnormal circadian rhythm detected a suggestive QTL, which affects the length of
      free-running period, on the distal region of Chromosome 19. Among the candidate
      genes, we have focused on Ikkalpha gene and found that Ikkalpha mRNA is expressed
      in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN) in the
      present study. Expression of Ikkalpha mRNA in the SCN indicated the possibility
      that IKKalpha is involved in the regulation of circadian clock. Therefore, to
      examine the role of IKKalpha in the regulation of circadian rhythms, we have
      further examined wheel-running activity rhythms under light-dark cycle and
      constant darkness, and circadian response to light. However, we could not detect
      any statistically significant difference between IKKalpha(+/-) mice and wild type
      mice. Roles of IKKalpha in the regulation of circadian system remains to be
      clarified in the future study.

PMID- 14642850
TI  - The effect of repetitive transcranial magnetic stimulation on long-term
      potentiation in rat hippocampus depends on stimulus intensity.
AB  - We investigated the effect of repetitive transcranial magnetic stimulation (rTMS)
      on long-term potentiation (LTP) in the rat hippocampus. Rats were magnetically
      stimulated at a rate of 1000 pulses/day for 7 days by a round coil, in which the
      peak magnetic fields at the center of the coil were 0.75 and 1.00 T. LTP
      enhancement was observed only in the 0.75-T rTMS group, while no change was
      observed in the 1.00-T rTMS group. These results suggest that the effect of rTMS
      on LTP depends on the stimulus intensity.

PMID- 14642851
TI  - Bilateral splanchnicotomy does not affect lipopolysaccharide-induced fever in
      rats.
AB  - Intraperitoneal capsaicin desensitizes sensory fibers traveling within both the
      vagus and splanchnic nerves. Because capsaicin desensitization blocks the first
      phase of lipopolysaccharide (LPS) fever, whereas surgical vagotomy does not,
      splanchnic mediation of the first phase was proposed. However, all phases of the
      febrile response of splanchnicotomized rats to intravenous LPS (10 microg/kg)
      were similar to those of sham-operated controls. Hence, the splanchnic nerve is
      likely uninvolved in LPS fever.

PMID- 14642852
TI  - 5-HT7 receptors increase the excitability of rat hippocampal CA1 pyramidal
      neurons.
AB  - In the CA1 area of rat hippocampal slices, a combined application of 5-CT, a
      potent 5-HT(1A) and 5-HT(7) receptor agonist, and WAY 100635, a selective 5
      HT(1A) receptor antagonist, resulted in a reversible increase of the CA1
      extracellular population spike amplitude. In whole-cell recording from identified
      pyramidal neurons, the effects of 5-CT applied in the presence of WAY 100635
      involved a reduction of the slow afterhyperpolarization (sAHP) and the frequency
      adaptation of action potential firing, which could be blocked by a specific 5
      HT(7) receptor antagonist SB 269970. The results indicate that the activation of
      5-HT(7) receptors increases the excitability of hippocampal CA1 pyramidal cells.

PMID- 14642853
TI  - Intracerebroventricular injection of muscimol, baclofen or nipecotic acid
      stimulates food intake in layer-type, but not meat-type, chicks.
AB  - This study was designed to compare the effects of muscimol (GABA(A) agonist),
      baclofen (GABA(B) agonist) and nipecotic acid (GABA uptake inhibitor) on food
      intake in two chicken strains (meat-type and layer-type chicks). The
      intracerebroventricular (ICV) injection of all GABA agents induced hyperphagia in
      layer-type chicks. However, in broiler chicks, there were similar tendencies with
      muscimol and nipecotic acid but not significantly different. Conversely, ICV
      injection of baclofen depressed feeding of broiler chicks. These results suggest
      that there are some differences in central GABAergic systems between these
      strains of chicks, but GABAergic systems have an important role in the regulation
      of food intake in neonatal chicks.

PMID- 14642855
TI  - Classification, epidemiology and aetiology.
AB  - Intestinal failure and its most important cause, short-bowel syndrome (SBS), are
      rare clinical entities leading to a vast complex of symptoms and complications
      with significant morbidity and mortality. Both conditions occur as the result of
      a massive reduction in enteral nutrient absorptive capacity. Disease
      manifestation is based on aetiological and anatomical characteristics such as
      remaining intestinal length and the presence of a functionally intact colon.
      Congenital and perinatal conditions, for example, intestinal atresia, necrotizing
      enterocolitis (NEC) and intestinal volvulus are the most important causes in
      children. The aetiology in adults is based on diseases inducing loss of
      intestinal function or loss of intestinal surface area after extensive surgical
      resections. The most frequent causes are mesenteric infarction, radiation
      enteritis and Crohn's disease. Knowledge of the epidemiology of intestinal
      failure and SBS is limited, being mainly based on the extrapolated figures of
      home parenteral nutrition centres and single-centre studies. At present, the
      incidence of SBS is estimated to be 2-5 per million.

PMID- 14642856
TI  - Indications for specific therapy in the rehabilitation of patients with the short
      bowel syndrome.
AB  - Diarrhoea, malabsorption and malnutrition characterize the short-bowel syndrome.
      Following the initial intestinal resection, complications such as fistulas and
      intra-abdominal abscesses may occur, but these usually resolve with appropriate
      surgical care. All residual intestine should be placed in continuity before
      serious attempts at rehabilitation with oral feedings are initiated. Small hourly
      oral feedings composed of food items high in complex carbohydrate and low in fat
      are started when appropriate and the diet is gradually increased as intestinal
      adaptation occurs. The goal during this process is to prevent diarrhoea and allow
      the formation of semiformed stools. With time, parenteral nutrition (PN) can be
      reduced, and the time required depends on both length of residual bowel and the
      particular anatomy involved-for example, the presence or absence of the colon. A
      programme of optimal diet plus growth hormone (0.1 mg/kg) and oral glutamine (30
      g/day) enhances the adaptive process and allows many patients independence from
      PN. However, those with extremely short segments of jejuno-ileum (<50 cm) and no
      colon have excessive fluid and electrolyte losses, and intestinal transplantation
      may be the only therapy which allows such patients to be independent of PN.

PMID- 14642857
TI  - Hepatobiliary, renal and bone complications of intestinal failure.
AB  - Abnormal liver function tests in patients with intestinal failure (IF) may be due
      to the underlying disease, IF or the treatments given (including parenteral
      nutrition (PN)). PN-related liver disease in children usually relates to
      intrahepatic cholestasis and in adults to steatosis. Steatosis may be consequent
      upon an excess of carbohydrate, lipid or protein, or upon a deficiency of a
      specific molecule. Pigment-type gallstones are common in adults and children with
      IF; these develop from biliary sludge that forms during periods of gallbladder
      stasis. Ileal disease/resection, parenteral nutrition, surgery, rapid weight loss
      and drugs all increase the risk of developing gallstones. Gallstone formation may
      be prevented by reducing gallbladder stasis (oral/enteral feeding or prokinetic
      agents), altering bile composition, or by means of a prophylactic
      cholecystectomy. Calcium oxalate renal stones are common in patients with a short
      bowel and retained functioning colon and are consequent upon increased absorption
      of dietary oxalate; they are prevented by a low-oxalate diet. An osteopathy may
      occur with long-term parenteral nutrition.

PMID- 14642858
TI  - Mortality and economics in short bowel syndrome.
AB  - The incidence of patients with short-bowel syndrome (SBS) has increased over the
      years due to progress of intensive care medicine and parenteral nutrition
      techniques. These techniques have significantly improved the prognosis of
      neonates, children and adults who have lost major parts of their intestinal
      tract. Long-term survival is possible and does not depend primarily on the length
      of the remaining bowel but on complications such as parenteral nutrition
      associated cholestasis, recurrent septicaemia, central venous catheter
      infections, and the motility of the remaining intestine. Thus, the overall
      related mortality in infants with SBS ranges from 15 to 25%, and in adults from
      15 to 47%, depending on the age of the patients, the underlying disease, and the
      duration on total parenteral nutrition. Home parenteral nutrition (HPN)
      significantly decreases the complication rate and improves the psychological
      situation of the patient. Additionally, HPN reduces in-hospital cost
      significantly. Nevertheless, the annual costs/patient are between $100000 and
      $150000. The mortality rate of SBS patients on HPN is about 30% after 5 years,
      which is still lower than the 5-year survival rate of intestinal grafts, and it
      is about equal to patients' survival after intestinal transplantation. However,
      the overall costs of a successful intestinal transplantation are already lower
      after 2 years when compared with the cost of a prolonged HPN programme.

PMID- 14642859
TI  - Intestinal absorption in health and disease--sugars.
AB  - Carbohydrates are mostly digested to glucose, fructose and galactose before
      absorption by the small intestine. Absorption across the brush border and
      basolateral membranes of enterocytes is mediated by sodium-dependent and 
      independent membrane proteins. Glucose and galactose transport across the brush
      border occurs by a Na(+)/glucose (galactose) co-transporter (SGLT1), whereas
      passive fructose transport is mediated by a uniporter (GLUT5). The passive exit
      of all three sugars out of the cell across the basolateral membrane occurs
      through two uniporters (GLUT2 and GLUT5). Mutations in SGLT1 cause a major defect
      in glucose and galactose absorption (glucose-galactose Malabsorption), but
      mutations in GLUT2 do not appear to disrupt glucose and galactose absorption.
      Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is
      another exit pathway for glucose and galactose that may involve exocytosis. There
      are no known defects of fructose absorption.

PMID- 14642860
TI  - Intestinal absorption in health and disease: micronutrients.
AB  - The main theme of this chapter concerns the precise biochemical mechanisms
      involved in stages up to, and including, gastrointestinal absorption of vitamins
      and certain selected minerals. Essential data regarding sequential events,
      immediately following absorption of these micronutrients, are also included.
      There is reference to water-soluble vitamins that are, in general, either
      coenzymes in various metabolic reactions or carriers of certain biochemical
      groupings. In contrast, fat-soluble vitamins frequently function as integral
      components of cell membranes; they, too, receive ample attention. It is
      appropriate, nevertheless, to recognize that some minerals required in very small
      amounts are closely allied biochemically with particular vitamins; these specific
      associations are apportioned emphasis at relevant places in the text. Although
      predominant discussion centres on the physiological state, clinical reference is
      necessarily made to gastrointestinal disorders in which imbalance of vitamins and
      minerals consequently results in an additional detrimental impact on health.

PMID- 14642861
TI  - Adaptation following intestinal resection: mechanisms and signals.
AB  - The intestine has an inherent ability to adapt morphologically and functionally
      in response to internal and external environmental changes. The functional
      adaptations encompass modifications of the brush border membrane fluidity and
      permeability, as well as up- or down-regulation of carrier-mediated transport.
      Intestinal adaptation improves the nutritional status following the loss of a
      major portion of the small intestine, following chronic ingestion of ethanol,
      following sublethal doses of abdominal irradiation, in diabetes, in pregnancy and
      lactation, with ageing, and with fasting and malnutrition. Following intestinal
      resection, morphological and functional changes occur depending upon the extent
      of the intestine removed, the site studied, and the lipid content of the diet.
      Therefore, intestinal adaptation has important implications in the survival
      potential and welfare of the host. An understanding of the mechanisms of, and
      signals for, intestinal adaptation in the experimental setting forms the basis
      for the use of management strategies in humans with the short-bowel syndrome.

PMID- 14642862
TI  - Enteral and parenteral nutrition in the care of patients with short-bowel
      syndrome.
AB  - Short-bowel syndrome is a challenging entity for the gastroenterologist,
      requiring integration of medical, nutritional, surgical and psychological
      therapies. Treatment must be based on the patient's age, remaining
      gastrointestinal anatomy, baseline nutritional status and underlying general
      health as well as the numerous complications which may arise. This chapter
      reviews physiological alterations that occur with short-bowel syndrome and how
      therapies can be tailored to most adequately meet the needs of these patients.
      Emphasis on early stages of therapy to enhance intestinal adaptation is focused
      on as management during this time has a significant impact on the long-term
      outcome of these patients.

PMID- 14642863
TI  - Surgical approaches and intestinal transplantation.
AB  - The surgical treatment of short-bowel syndrome has been traditionally based on
      the correction of mechanical obstruction, which is responsible for bacterial
      overgrowth syndrome, or on intestinal expansion procedures. Since the
      introduction of clinical intestinal transplantation by Lillehei in 1964, there
      have been remarkable advances in the immunosuppressive regimens to control
      rejection and in preservation techniques, monitoring and critical care. Newer and
      more powerful immunosuppressants have helped to transform intestinal
      transplantation into a clinical reality-transplantation can now be a life-saving
      procedure for patients with intestinal failure. It is currently indicated in the
      event of life-threatening complications of an underlying disease or from total
      parenteral nutrition (TPN). Rehabilitation in successful cases is excellent.

PMID- 14642864
TI  - Experimental approaches: dietary and hormone therapy.
AB  - Patients who suffer from intestinal failure depend on parenteral support to
      maintain nutritional equilibrium. In this chapter, recommendations for evaluation
      the absorptive capacity of patients with intestinal failure are defined, and the
      evidence and magnitude of the effect of dietary and hormone therapy is given.
      Regarding dietary advice, the effects of employment of diets with various
      carbohydrate:fat ratios in short-bowel syndrome (SBS) patients with and without a
      preserved colon is presented. Focus has been placed on the use of growth hormone
      but also on the use of a novel intestinotrophic hormone, glucagon-like peptide 2,
      in the promotion of intestinal adaptation in SBS patients. Overall, the ultimate
      aim in the treatment of SBS patients is to optimize remnant intestinal function,
      thereby eliminating the need for parenteral support and improving quality of life
      in these patients.

PMID- 14642866
TI  - Effect of insulin and contraction up on glucose transport in skeletal muscle.
AB  - The major glucose transporter protein expressed in skeletal muscle is GLUT4. Both
      muscle contraction and insulin induce translocation of GLUT4 from the
      intracellular pool to the plasma membrane. The intracellular pathways that lead
      to contraction- and insulin-stimulated GLUT4 translocation seem to be different,
      allowing the attainment of a maximal effect when acting together. Insulin
      utilizes a phosphatidylinositol 3-kinase-dependent mechanism, whereas the
      exercise signal may be initiated by calcium release from the sarcoplasmic
      reticulum or from autocrine- or paracrine-mediated activation of glucose
      transport. During exercise skeletal muscle utilizes more glucose than when at
      rest. However, endurance training leads to decreased glucose utilization during
      sub-maximal exercise, in spite of a large increase in the total GLUT4 content
      associated with training. The mechanisms involved in this reduction have not been
      totally elucidated, but appear to cause the decrease of the amount of GLUT4
      translocated to the plasma membrane by altering the exercise-induced enhancement
      of glucose transport capacity. On the other hand, the effect of resistance
      training is controversial. Recent studies, however, demonstrated the improvement
      in insulin sensitivity correlated with increasing muscle mass. New studies should
      be designed to define the molecular basis for these important adaptations to
      skeletal muscle. Since during exercise the muscle may utilize insulin-independent
      mechanisms to increase glucose uptake, the mechanisms involved should provide
      important knowledge to the understanding and managing peripheral insulin
      resistance.

PMID- 14642867
TI  - Cytoskeletal modulation of electrical and mechanical activity in cardiac
      myocytes.
AB  - The cardiac myocyte has an intracellular scaffold, the cytoskeleton, which has
      been implicated in several cardiac pathologies including hypertrophy and failure.
      In this review we describe the role that the cytoskeleton plays in modulating
      both the electrical activity (through ion channels and exchangers) and mechanical
      (or contractile) activity of the adult heart. We focus on the 3 components of the
      cytoskeleton, actin microfilaments, microtubules, and desmin filaments. The
      limited visual data available suggest that the subsarcolemmal actin cytoskeleton
      is sparse in the adult myocyte. Selective disruption of cytoskeletal actin by
      pharmacological tools has yet to be verified in the adult cell, yet evidence
      exists for modulation of several ionic currents, including I(CaL), I(Na),
      I(KATP), I(SAC) by actin microfilaments. Microtubules exist as a dense network
      throughout the adult cardiac cell, and their structure, architecture, kinetics
      and pharmacological manipulation are well described. Both polymerised and free
      tubulin are functionally significant. Microtubule proliferation reduces
      contraction by impeding sarcomeric motion; modulation of sarcoplasmic reticulum
      Ca(2+) release may also be involved in this effect. The lack of effect of
      microtubule disruption on cardiac contractility in adult myocytes, and the
      concentration-dependent modulation of the rate of contraction by the disruptor
      nocodazole in neonatal myocytes, support the existence of functionally distinct
      microtubule populations. We address the controversy regarding the stimulation of
      the beta-adrenergic signalling pathway by free tubulin. Work with mice lacking
      desmin has demonstrated the importance of intermediate filaments to normal
      cardiac function, but the precise role that desmin plays in the electrical and
      mechanical activity of cardiac muscle has yet to be determined.

PMID- 14642868
TI  - Segmentation and zooid formation in animals with a posterior growing region: the
      case for metabolic gradients and Turing waves.
AB  - The discovery of periodic propagation of anteriorly moving pulses/stripes of gene
      expression in the presomitic mesoderm (PSM) of vertebrates has given new life to
      the clock and wavefront model, and other models of morphogenesis based on a
      molecular oscillator where the time periodicity is translated into spatial
      periodicity. Instead we suggest that segmentation, somitogenesis and metamerism
      in vertebrates and in invertebrates with a posterior growing region are based on
      a Turing-Child metabolic gradient that is progressively shifted posteriorly with
      the PSM as elongation, segmentation and somitogenesis proceed. This gradient
      corresponds to anteriorly propagating metabolic front in the PSM that drives the
      anteriorly propagating mRNA synthesis and which, together with mRNA degradation,
      explains stripe formation and spatial periodicity.The process of segmentation has
      been compared to zooid formation. We show that for annelids the metabolic profile
      behaves as a Turing field in the sense that an increase in the length of the
      system or a decrease of the Turing wavelength results in an additional peak in
      the posterior growing region as predicted by Turing theory. In particular, it is
      shown that the metabolic gradient that drives the segmentation is based on a
      Turing system.

PMID- 14642869
TI  - Differences in male and female injury severities in sport-utility vehicle,
      minivan, pickup and passenger car accidents.
AB  - This research explores differences in injury severity between male and female
      drivers in single and two-vehicle accidents involving passenger cars, pickups,
      sport-utility vehicles (SUVs), and minivans. Separate multivariate multinomial
      logit models of injury severity are estimated for male and female drivers. The
      models predict the probability of four injury severity outcomes: no injury
      (property damage only), possible injury, evident injury, and fatal/disabling
      injury. The models are conditioned on driver gender and the number and type of
      vehicles involved in the accident. The conditional structure avoids bias caused
      by men and women's different reporting rates, choices of vehicle type, and their
      different rates of participation as drivers, which would affect a joint model of
      all crashes. We found variables that have opposite effects for the genders, such
      as striking a barrier or a guardrail, and crashing while starting a vehicle. The
      results suggest there are important behavioral and physiological differences
      between male and female drivers that must be explored further and addressed in
      vehicle and roadway design.

PMID- 14642870
TI  - Traffic safety assessment and development of predictive models for accidents on
      rural roads in Egypt.
AB  - This paper starts by presenting a conceptualization of indicators, criteria and
      accidents' causes that can be used to describe traffic safety. The paper provides
      an assessment of traffic safety conditions for rural roads in Egypt. This is done
      through a three-step procedure. First, deaths per million vehicle kilometers are
      obtained and compared for Egypt, three other Arab countries and six of the G-7
      countries. Egypt stands as having a significantly high rate of deaths per 100
      million vehicle kilometers. This is followed by compiling available traffic and
      accident data for five main rural roads in Egypt over a 10-year period (1990
      1999). These are used to compute and compare 13 traffic safety indicators for
      these roads. The third step for assessing traffic safety for rural roads in Egypt
      is concerned with presenting a detailed analysis of accident causes. The paper
      moves on to develop a number of statistical models that can be used in the
      prediction of the expected number of accidents, injuries, fatalities and
      casualties on the rural roads in Egypt. Time series data of traffic and
      accidents, over a 10 years period for the considered roads, is utilized in the
      calibration of these predictive models. Several functional forms are explored and
      tested in the calibration process. Before proceeding to the development of these
      models three ANOVA statistical tests are conducted to establish whether there are
      any significant differences in the data used for models' calibration as a result
      of differences among the considered five roads.

PMID- 14642871
TI  - Computerized coding of injury narrative data from the National Health Interview
      Survey.
AB  - OBJECTIVE: To investigate the accuracy of a computerized method for classifying
      injury narratives into external-cause-of-injury and poisoning (E-code)
      categories. METHODS: This study used injury narratives and corresponding E-codes
      assigned by experts from the 1997 and 1998 US National Health Interview Survey
      (NHIS). A Fuzzy Bayesian model was used to assign injury descriptions to 13 E
      code categories. Sensitivity, specificity and positive predictive value were
      measured by comparing the computer generated codes with E-code categories
      assigned by experts. RESULTS: The computer program correctly classified 4695
      (82.7%) of the 5677 injury narratives when multiple words were included as
      keywords in the model. The use of multiple-word predictors compared with using
      single words alone improved both the sensitivity and specificity of the computer
      generated codes. The program is capable of identifying and filtering out cases
      that would benefit most from manual coding. For example, the program could be
      used to code the narrative if the maximum probability of a category given the
      keywords in the narrative was at least 0.9. If the maximum probability was lower
      than 0.9 (which will be the case for approximately 33% of the narratives) the
      case would be filtered out for manual review. CONCLUSIONS: A computer program
      based on Fuzzy Bayes logic is capable of accurately categorizing cause-of-injury
      codes from injury narratives. The capacity to filter out certain cases for manual
      coding improves the utility of this process.

PMID- 14642872
TI  - Corporate cost of occupational accidents: an activity-based analysis.
AB  - The systematic accident cost analysis (SACA) project was carried out during 2001
      by The Aarhus School of Business and PricewaterhouseCoopers Denmark with
      financial support from The Danish National Working Environment Authority. Its
      focused on developing and testing a method for evaluating occupational costs of
      companies for use by occupational health and safety professionals. The method was
      tested in nine Danish companies within three different industry sectors and the
      costs of 27 selected occupational accidents in these companies were calculated.
      One of the main conclusions is that the SACA method could be used in all of the
      companies without revisions. The evaluation of accident cost showed that 2/3 of
      the costs of occupational accidents are visible in the Danish corporate
      accounting systems reviewed while 1/3 is hidden from management view. The highest
      cost of occupational accidents for a company with 3.600 employees was estimated
      to approximately US$ 682.000. The paper includes an introduction regarding
      accident cost analysis in companies, a presentation of the SACA project
      methodology and the SACA method itself, a short overview of some of the results
      of the SACA project and a conclusion. Further information about the project is
      available at http://www.asb.dk/saca.

PMID- 14642873
TI  - Selecting exposure measures in crash rate prediction for two-lane highway
      segments.
AB  - A critical part of any risk assessment is identifying how to represent exposure
      to the risk involved. Recent research shows that the relationship between crash
      count and traffic volume is non-linear; consequently, a simple crash rate
      computed as the ratio of crash count to volume is not proper for comparing the
      safety of sites with different traffic volumes. To solve this problem, we
      describe a new approach for relating traffic volume and crash incidence.
      Specifically, we disaggregate crashes into four types: (1) single-vehicle, (2)
      multi-vehicle same direction, (3) multi-vehicle opposite direction, and (4) multi
      vehicle intersecting, and define candidate exposure measures for each that we
      hypothesize will be linear with respect to each crash type. This paper describes
      initial investigation using crash and physical characteristics data for highway
      segments in Michigan from the Highway Safety Information System (HSIS). We use
      zero-inflated-Poisson (ZIP) modeling to estimate models for predicting counts for
      each of the above crash types as a function of the daily volume, segment length,
      speed limit and roadway width. We found that the relationship between crashes and
      the daily volume (AADT) is non-linear and varies by crash type, and is
      significantly different from the relationship between crashes and segment length
      for all crash types. Our research will provide information to improve accuracy of
      crash predictions and, thus, facilitate more meaningful comparison of the safety
      record of seemingly similar highway locations.

PMID- 14642874
TI  - An accident waiting to happen: a spatial approach to proactive pedestrian
      planning.
AB  - There are about 75,000 pedestrian crashes in the United States each year.
      Approximately 5000 of these crashes are fatal, accounting for 12% of all roadway
      deaths. On college campuses, pedestrian exposure and crash-risk can be quite
      high. Therefore, we analyzed pedestrian crashes on the campus of the University
      of North Carolina at Chapel Hill (UNC) as a test case for our spatially-oriented
      prototype tool that combines perceived-risk (survey) data with police-reported
      crash data to obtain a more complete picture of pedestrian crash-risk. We use
      spatial analysis techniques combined with regression models to understand factors
      associated with risk. The spatial analysis is based on comparing two
      distributions, i.e. the locations of perceived-risk with police-reported crash
      locations. The differences between the two distributions are statistically
      significant, implying that certain locations on campus are perceived as
      dangerous, though pedestrian crashes have not yet occurred there, and there are
      actual locations of police-reported crashes that are not perceived to be
      dangerous by pedestrians or drivers. Furthermore, we estimate negative binomial
      regression models to combine pedestrian and automobile exposure with roadway
      characteristics and spatial/land use information. The models show that high
      exposure, incomplete sidewalks and high crosswalk density are associated with
      greater observed and perceived pedestrian crash-risk. Additionally, we found that
      people perceive a lower risk near university libraries, stadiums, and academic
      buildings, despite the occurrence of crashes.

PMID- 14642875
TI  - The effect of crash experience on changes in risk taking among urban and rural
      young people.
AB  - A 20-month prospective study was conducted to investigate the effect of
      motorcycle crash experience on changes in risk taking among 2514 urban and 2304
      rural students in Taiwan. Risk taking was assessed using a 14-item self
      administered questionnaire at the beginning and end of the study. A risk-taking
      score for each student at the initial and the last follow-up assessments was
      generated from adding up points across all 14 items. For exposure variables, the
      study documented past motorcycle crash history at the initial assessment and
      collected detailed information about any motorcycle crash involvement that
      occurred during the study period. A general linear mixed model was applied to
      assess the effects of prior and recent crash involvements on the path of risk
      taking behavior. The results show that at the initial assessment, students with
      crash experience had higher risk-taking levels than those without crash
      experience. However, crash experience, irregardless of whether it was measured in
      terms of crash history prior to the study, crash frequency, time elapsed since
      the last crash, or crash severity, did not significantly change the risk-taking
      path among students, even though its effect differed between urban and rural
      areas.

PMID- 14642876
TI  - Effect of repeal of the national maximum speed limit law on occurrence of
      crashes, injury crashes, and fatal crashes on Utah highways.
AB  - Speed limits were increased in Utah and other States after repeal of the national
      maximum speed limit law (NMSL) in 1995. This study analyzed effects of the
      increased speed limit on Utah highways on crash rates, fatality crash rates, and
      injury crash rates. Annual (1992-1999) rates of crashes, fatality crashes, and
      injury crashes for the following highway categories were calculated: urban
      Interstate segments (current speed limit 60-65 miles per hour (mph)); rural
      Interstate segments (current speed limit 70-75 mph); 55 mph rural non-Interstate
      highway segments; and high-speed non-Interstate highways (current speed limit 60
      65 mph). Data were analyzed using autoregressive integrative moving average
      intervention time series analysis techniques. There were significant increases in
      total crash rates on urban (60-65 mph) Interstate segments (confounded by
      extensive ongoing highway construction on these highways), and in fatal crash
      rates on high-speed (60-65 mph) rural non-Interstate segments. The following
      variables were unaffected: total, fatality, and injury crash rates on rural
      Interstate segments; fatality and injury crash rates on urban Interstate
      segments; total and injury crash rates on high-speed non-Interstate segments.
      These results show an adverse effect on crash occurrence for subsets of crash
      types and highways, but do not show a major overall effect of NMSL repeal and
      increased speed limit on crash occurrence on Utah highways.

PMID- 14642877
TI  - The Manchester Driver Behaviour Questionnaire: a cross-cultural study.
AB  - The aim of the present study was to investigate if the original factorial
      structure of the Manchester Driver Behaviour Questionnaire (DBQ) was replicated
      in Finland and The Netherlands. A postal questionnaire survey of drivers was
      carried out in Britain, Finland and The Netherlands. Exploratory factor analysis
      together with target (Procrustes) rotation and factorial agreement indexes were
      calculated to investigate the applicability of Finnish and Dutch versions of DBQ.
      Results of the factor comparisons showed that the DBQ four-factor structures
      found in Finland and The Netherlands were congruent but not perfect with the
      target structure found in Britain. Reliabilities of the scales were around the
      same level as in the British data. In addition to the four first-order factors,
      two second-order factors (deliberate violations and unintentional errors) were
      found in all three countries which supports the original structure by Reason et
      al. Issues related to cross-cultural use of traffic behaviour questionnaires are
      discussed.

PMID- 14642878
TI  - The involvement of drugs in drivers of motor vehicles killed in Australian road
      traffic crashes.
AB  - A multi-center case-control study was conducted on 3398 fatally-injured drivers
      to assess the effect of alcohol and drug use on the likelihood of them being
      culpable. Crashes investigated were from three Australian states (Victoria, New
      South Wales and Western Australia). The control group of drug- and alcohol-free
      drivers comprised 50.1% of the study population. A previously validated method of
      responsibility analysis was used to classify drivers as either culpable or non
      culpable. Cases in which the driver "contributed" to the crash (n=188) were
      excluded. Logistic regression was used to examine the association of key
      attributes such as age, gender, type of crash and drug use on the likelihood of
      culpability. Drivers positive to psychotropic drugs were significantly more
      likely to be culpable than drug-free drivers. Drivers with Delta(9)
      tetrahydrocannabinol (THC) in their blood had a significantly higher likelihood
      of being culpable than drug-free drivers (odds ratio (OR) 2.7, 95% CI 1.02-7.0).
      For drivers with blood THC concentrations of 5 ng/ml or higher the odds ratio was
      greater and more statistically significant (OR 6.6, 95% CI 1.5-28.0). The
      estimated odds ratio is greater than that for drivers with a blood alcohol
      concentration (BAC) of 0.10-0.15% (OR 3.7, 95% CI 1.5-9.1). A significantly
      stronger positive association with culpability was seen with drivers positive to
      THC and with BAC > or =0.05% compared with BAC > or =0.05 alone (OR 2.9, 95% CI
      1.1-7.7). Strong associations were also seen for stimulants, particularly in
      truck drivers. There were non-significant, weakly positive associations of
      opiates and benzodiazepines with culpability. Drivers positive to any
      psychoactive drug were significantly more likely to be culpable (OR 1.8, 95% CI
      1.3-2.4). Gender differences were not significant, but differences were apparent
      with age. Drivers showing the highest culpability rates were in the under 25 and
      over 65 age groups.

PMID- 14642879
TI  - Trends of behavioral risk factors in motor vehicle crashes in Utah, 1992-1997.
AB  - OBJECTIVE: Measure changes in the prevalence of behavioral factors including
      police-reported fatigue and alcohol intoxication, as well as self-reported
      seatbelt use, and assess their effect on hospitalization or death after a motor
      vehicle crash. METHODS: Probabilistic linkage was used to match drivers in motor
      vehicle crashes with hospital discharge records for the years 1992-1997.
      Frequencies of specific behavioral factors were evaluated using the Cochran
      Armitage test for trend. Odds ratios and corresponding 95% confidence intervals
      were calculated using generalized estimating equations (GEEs) with crash and
      driver characteristics as independent variables and hospitalization or death as
      the dependent variable. RESULTS: The analysis database consisted of 450,286 crash
      driver records, which linked to 4219 (0.9%) hospitalizations or deaths. There was
      an increasing trend for self-reported seatbelt use among crash-involved drivers
      from 80.5% in 1992 to 89.3% in 1997 (P<0.001). Police-reported alcohol
      intoxication among crash-involved drivers showed a decreasing trend from 2.4% in
      1992 to 1.5% in 1997 (P<0.001). There was no trend for police-reported fatigue
      related crashes. Odds ratios of hospitalization or death for seatbelt use,
      alcohol involvement, and fatigue were significant and did not fluctuate
      considerably between 1992 and 1997. Seatbelt use offered a protective effect from
      hospitalization or death, while alcohol intoxication and fatigue contributed to
      increased likelihood of hospitalization or death. CONCLUSIONS: These results
      suggest that while some improvement has been made in decreasing seatbelt non-use
      and driver alcohol intoxication among crash-involved drivers, no improvement has
      been made in reducing fatigue-related crashes.

PMID- 14642880
TI  - Passenger seating position and the risk of passenger death or injury in traffic
      crashes.
AB  - OBJECTIVE: To estimate the association of passenger seat position with the risk
      of death and serious injury for passengers in traffic crashes. METHODS: Using
      1993-2000 data from the National Highway Traffic Safety Administration's
      Crashworthiness Data System (CDS), the risk ratio for death and serious injury
      was estimated for rear seat passengers compared with front seat passengers in
      motor vehicle crashes. RESULTS: The adjusted risk ratio for death of passengers
      in the rear seat in a crash was 0.61 (95% confidence interval (CI) 0.46-0.81).
      Rear seat passenger position was also associated with a decrease in the risk of
      death and serious injury compared with the front seat passenger position: risk
      ratio=0.67 (95% CI 0.57-0.78). CONCLUSION: We estimated that the rear seat
      passenger position may reduce the risk of death in a motor vehicle crash by about
      39% and reduce the risk of death or serious injury in a crash by 33%, compared
      with the front seat passenger position. If the associations that we report are
      causal, sitting in the rear seat, compared with the front seat, may prevent about
      4 in 10 passenger deaths, or 3 in 10 passenger deaths and injuries, that might
      otherwise occur.

PMID- 14642882
TI  - Driver behaviour during flashing green before amber: a comparative study.
AB  - The paper discusses the results of extensive measurements of drivers' stopping
      behaviour during signal programmes with and without flashing green before amber.
      Ten locations in Switzerland, Austria, and Germany were recorded with a video
      camera and analysed using an image-processing system. About 5000 cycles were
      documented. The analysis shows that the flashing green increases the number of
      early stops, as drivers tend to underestimate the duration of the time to the end
      of amber. Discrete choice models of the stopping behaviour are estimated for
      inclusion in suitable microsimulation models of traffic flow. The model results
      show that speed and distance to stop line, and their interaction (potential time
      to the stop line with unchanged speed) explain the stopping process.

PMID- 14642881
TI  - Boarding and alighting injury experience with different station platform and car
      entranceway designs on US commuter railroads.
AB  - Commuter railroad systems in the US employ three combinations of station
      platforms and car entranceways. These are high-level platforms with remotely
      controlled doors and level entranceway (HL-RC), low-level platforms (just above
      the rail) with steps and remotely controlled doors (LL-RC), and a mixture of the
      two platform types with a correspondingly more complex, partly manual, door and
      entranceway arrangement (ML-MO). Much controversy exists over which type of
      platform/entranceway is better. This seemingly small feature significantly
      impacts many performance characteristics of these systems, including cost, speed,
      and boarding and alighting accidents. Northeastern systems are generally moving
      toward the mixed platform design or all high-level platforms, while systems
      elsewhere are generally selecting the low-level design. Data on actual accident
      experience for 1995-2000 are analyzed to determine the effect of
      platform/entranceway type on passenger and employee injuries. Passenger injury
      rates on systems with the HL-RC design are lowest, with LL-RC systems next, and
      ML-MO systems having the highest rates. Employee injury rates are the least on LL
      RC systems, but higher on ML-MO and HL-RC systems. Systems with a mixture of high
      and low platforms (ML-MO) experience a higher overall (combined passenger and
      employee) injury rate than the other two designs. The implications of these
      results for both the modernization of existing systems and the design of new
      systems, in the US and abroad, are discussed.

PMID- 14642883
TI  - A qualitative assessment methodology for road safety policy strategies.
AB  - This paper proposes a qualitative assessment methodology that is comprised of a
      cluster analysis and an autoregression analysis that assess the effects of
      various road safety strategies implemented in Hong Kong over the last 10 years.
      The cluster analysis is first used to group over a hundred road safety projects
      and programs into a smaller set of meaningful road safety policy strategy
      clusters. These strategies, together with the trend factor, seasonal pattern, car
      crashworthiness and meteorological data are then used in the autoregression
      analysis to relate to the fatality and casualty rates of drivers, passengers,
      motorcyclists, and pedestrians. This method allows the evaluation of the overall
      effects of the road safety strategies, and the effects and relative significance
      of each individual strategy. The evaluation method is described, and the main
      findings of the study are discussed.

PMID- 14642884
TI  - The fatality and injury risk of light truck impacts with pedestrians in the
      United States.
AB  - In the United States, passenger vehicles are shifting from a fleet populated
      primarily by cars to a fleet dominated by light trucks and vans (LTVs). Because
      light trucks are heavier, stiffer, and geometrically more blunt than passenger
      cars, they pose a dramatically different type of threat to pedestrians. This
      paper investigates the effect of striking vehicle type on pedestrian fatalities
      and injuries. The analysis incorporates three major sources of data, the Fatality
      Analysis Reporting System (FARS), the General Estimates System (GES), and the
      Pedestrian Crash Data Study (PCDS). The paper presents and compares pedestrian
      impact risk factors for sport utility vehicles, pickup trucks, vans, and cars as
      developed from analyses of US accident statistics. Pedestrians are found to have
      a two to three times greater likelihood of dying when struck by an LTV than when
      struck by a car. Examination of pedestrian injury distributions reveals that,
      given an impact speed, the probability of serious head and thoracic injury is
      substantially greater when the striking vehicle is an LTV rather than a car.

PMID- 14642886
TI  - Cysteine-rich antimicrobial peptides of the cattle tick Boophilus microplus:
      isolation, structural characterization and tissue expression profile.
AB  - Antimicrobial peptides (AMPs) are components of the immune system of both
      vertebrate and invertebrate animals. This study describes the isolation, primary
      structure, cDNA cloning, and tissue expression profile of two cysteine-rich AMPs
      from the hemolymph of the cattle tick Boophilus microplus. A 10,204 Da
      polypeptide, with six cysteine residues and no sequence similarity to any known
      molecule, was isolated from the cell-free hemolymph. Because of its sequence
      originality, this peptide was named microplusin. The second AMP was isolated from
      the hemocytes of B. microplus. This peptide, with a molecular mass of 4285 Da and
      six cysteines, is a defensin with similarity to the insect defensin family
      members. The cDNA cloning established that microplusin is synthesized as a
      prepeptide while the tick defensin is synthesized as a prepromolecule.
      Interestingly, despite the fact that microplusin and defensin have been isolated
      from different compartments, their gene expression was found to have similar
      tissue distribution.

PMID- 14642885
TI  - Exocytosis of a complement component C3-like protein by tunicate hemocytes.
AB  - This study investigates the exocytic responses of invertebrate hemocytes to
      pathogen-associated antigens. It demonstrates that a homologue of complement
      component C3, a key defensive protein of the innate immune system, is expressed
      by phagocytic hemocytes (non-refractile vacuolated cells) of the tunicate, Styela
      plicata. C3-like molecules are localized in sub-cellular vesicles and are rapidly
      exocytosed after stimulation with bacterial, fungal or algal cell surface
      molecules. Signal transduction analysis indicated that the induced secretion of
      C3-like molecules is mediated by a G-protein dependent signaling pathway, which
      modulates tubulin microtubules. All of this evidence indicates that hemocytes can
      contribute to host defense responses by rapidly exocytosing C3-like proteins at
      sites of infection.

PMID- 14642887
TI  - Continuous development precludes radioprotection in a colonial ascidian.
AB  - Colonial organisms provide a unique experimental system for stem cell biology.
      The colonial Urochordate Botryllus schlosseri reproduces sexually as well as by
      continuous asexual budding. Adjacent colonies with a shared histocompatibility
      allele undergo vascular fusion and establish a common blood circulation,
      performing natural transplantation. Fused colonies become chimeras, often with
      complete somatic replacement of the host cell genotype by the fused parabiont. We
      attempted to establish a radioprotection assay for the somatic stem cells that
      induce long-term chimerism in Botryllus. We demonstrate over a range of radiation
      doses that neither autologous nor allogeneic cell transplantation enhances
      survival of host colonies. This suggests that high mitotic index associated with
      continuous asexual development leads to radiosensitivity of organs and structures
      essential to survival during engraftment. We observe that radiation induces
      uncontrolled epithelial cell proliferation in abnormally terminated buds,
      suggesting that stem cells are not required for the initial stages of bud
      development.

PMID- 14642888
TI  - Molecular characterization and IFN signal pathway analysis of Carassius auratus
      CaSTAT1 identified from the cultured cells in response to virus infection.
AB  - Type I interferon (IFN) exerts its pleiotropic effects mainly through the JAK
      STAT signaling pathway, which is presently best described in mammals. By
      subtractive suppression hybridization, two fish signaling factors, JAK1 and
      STAT1, had been identified in the IFN-induced crucian carp Carassius auratus L.
      blastulae embryonic (CAB) cells after treatment with UV-inactivated grass carp
      hemorrhagic virus (GCHV). Further, the full-length cDNA of STAT1, termed CaSTAT1,
      was obtained. It contains 2926 bp and encodes a protein of 718 aa. CaSTAT1 is
      most similar to rat STAT1 with 59% identity overall and displays all highly
      conserved domains that the STAT family possesses. Like human STAT1beta, it lacks
      the C-terminus acting as transcriptional activation domain in mammals. By
      contrast, only a single transcript was detected in virus-induced CAB cells.
      Expression analysis showed that CaSTAT1 could be activated by stimulation of CAB
      cells with poly I:C, active GCHV, UV-inactivated GCHV or CAB IFN, and displayed
      diverse expression patterns similar to that of mammalian STAT1. Additionally, the
      expression of an antiviral gene CaMx1 was also induced under the same conditions,
      and expression difference between CaSTAT1 and CaMx1 was revealed by induction of
      CAB IFN. These results provide molecular evidence supporting the notion that the
      fish IFN signaling transduction pathway is similar to that in mammals. Fish IFN
      exerts its multiple functions, at least antiviral action, through a JAK-STAT
      pathway.

PMID- 14642889
TI  - Production and mechanism of secretion of interleukin-1beta from the marine fish
      gilthead seabream.
AB  - Mammalian interleukin-1beta (IL-1beta) is a secretory cytokine lacking a signal
      peptide, which does not follow the classical endoplasmic reticulum to Golgi
      pathway of secretion. Its post-translational processing by IL-1beta-converting
      enzyme (ICE) and subsequent release from activated macrophages requires ATP
      acting on P2X7 receptors. Little information is available on the production and
      release of fish IL-1beta, but the IL-1beta gene sequences reported to date lack a
      conserved ICE recognition site. We show for the first time that
      lipopolysaccharide (LPS)/macrophage-activating factor/bacterial DNA (VaDNA)
      primed immune cells of the marine fish gilthead seabream (Sparus aurata)
      accumulate intracellular IL-1beta as a approximately 30 kDa polypeptide (proIL
      1beta). The combination of LPS and VaDNA was found to be synergistic, suggesting
      that each ligand is recognized by a different pattern recognition receptor. More
      importantly, addition of extracellular ATP does not promote IL-1beta secretion by
      immune cells and fails to induce phosphatidylserine flip. In contrast, gilthead
      seabream SAF-1 fibroblasts shed microvesicles containing a 22 kDa IL-1beta form
      within 30 min of activation with ATP. Notably, the post-translational processing
      of IL-1beta by SAF-1 cells is abrogated by a specific ICE inhibitor.

PMID- 14642890
TI  - 2E3, a new marker that selectively identifies porcine CD4+ naive T cells.
AB  - We describe a novel antigen recognized by mAb 2E3 selectively expressed in the
      periphery by a subset of porcine CD4+ T cells. Both, CD4+CD8alpha- and
      CD4+CD8alphalow T cell subpopulations express this antigen. CD4+2E3+ T cells show
      phenotypical and functional characteristics of nai;ve cells. The majority of them
      are CD29low, CD45RAhigh, CD49dlow, CD11alow, CD18low, and SLA-II-. After mitogen
      activation CD4+2E3+ T cells express high levels of IL-2 mRNA, but only traces of
      IFN-gamma or IL-4 mRNA. Indeed a minor percentage of cells stained positive for
      IFN-gamma when assessed by flow cytometry. Moreover, CD4+2E3+ T cells did not
      proliferate in response to the recall antigen lysozyme, although they did
      efficiently to the mitogen ConA. By contrast, CD4+2E3- T cells show phenotypical
      and functional characteristics of primed cells. They express markers associated
      to a memory phenotype, respond to the recall antigen lysozyme, and produce high
      amounts of IFN-gamma and IL-4.

PMID- 14642891
TI  - The equine thymus microenvironment: a morphological and immunohistochemical
      analysis.
AB  - We characterized herein the microarchitecture of the equine thymus along with
      post-natal development (6 months-->18 years). Thymuses showed an involutional
      process, beginning before the puberty and defined by five histological grades,
      which consider the progressive cortical thymocyte depletion, shrinkage and
      rearrangement of the epithelial network and increase in extracellular matrix
      (ECM). A second feature of the equine thymus was the presence of eosinopoiesis,
      erythropoiesis, mastocytopoiesis and plasmacytogenesis. Additionally, lymphatic
      vessels, full of lymphocytes, were particularly prominent. Distribution of ECM
      proteins was heterogeneous, being denser in the medulla, as well as basement
      membranes of capsule, septa and perivascular spaces, thus similar to the patterns
      seen in other mammals. In vitro, horse thymic nurse cells produce ECM proteins,
      which are relevant in thymocyte/epithelial cell interactions. In conclusion, the
      equine thymus presents morphological and involutional characteristics similar to
      other mammals, exhibiting particular features, as prominent non-lymphoid
      hematopoiesis and lymphatic vessels.

PMID- 14642892
TI  - Sequence analysis of the MHC class II DRB alleles in Alpine chamois (Rupicapra r.
      rupicapra).
AB  - This study characterises the expressed MHC class II DRB gene and its genetic
      variation in exon 2 among 59 Alpine chamois (Rupicapra r. rupicapra) from several
      locations in the Eastern Alps plus one population in the Western Alps. The
      expressed DRB gene contains all the expected characteristics including all of the
      conserved residues found in other mammalian species. The isolated expressed DRB
      gene from chamois can be considered orthologous to MHC class II DRB genes in
      other mammalian species. Cattle primers yielded exon 2 sequences of 284 bp
      length. Sequence analysis revealed 19 DRB exon 2 alleles among 59 chamois.
      Alleles exhibited a high degree of nucleotide and amino acid polymorphism, with
      most amino acid variations occurring at positions forming the peptide-binding
      sites. A significantly higher rate of non-synonymous (dN = 0.053+/-0.0132) than
      synonymous (dS = 0.007+/-0.003) substitutions indicated positive selection for
      diversity in the DRB locus.

PMID- 14642894
TI  - Relative image size, not eye position, determines eye dominance switches.
AB  - A recent paper examined eye dominance with the eyes in forward and eccentric gaze
      [Vision Res. 41 (2001) 1743]. When observers were looking to the left, the left
      eye tended to dominate and when they were looking to the right, the right eye
      tended to dominate. The authors attributed the switch in eye dominance to extra
      retinal signals associated with horizontal eye position. However, when one looks
      at a near object on the left, the image in the left eye is larger than the one in
      the right eye, and when one looks to the right, the opposite occurs. Thus,
      relative image size could also trigger switches in eye dominance. We used a cue
      conflict paradigm to determine whether eye position or relative image size is the
      determinant of eye-dominance switches with changes in gaze angle. When eye
      position and relative image size were varied independently, there was no
      consistent effect of eye position. Relative image size appears to be the sole
      determinant of the switch.

PMID- 14642895
TI  - Events before the flash Do influence the flash-lag magnitude.
AB  - The flash-lag effect occurs when a flash abreast of a smoothly moving object is
      perceived to spatially lag the moving object. The postdiction accounts of this
      effect assume either that the flash "resets" motion detectors [Science 287 (2000)
      2036], or that position information is not computed for moving objects until it
      is needed [Trends in the Neurosciences 25 (2002) 293], the latter view having
      also been proposed by Brenner and Smeets [Vision Research 40 (2000) 1645].
      According to these accounts, events occurring before the flash should not change
      the magnitude of the flash-lag effect. In our experiment, pre-exposure of the
      moving object as a stationary stimulus, for as little as 50 ms before the flash
      occurred, significantly reduced the flash-lag effect.

PMID- 14642896
TI  - Illusory reversal of temporal order: the bias to report a dimmer stimulus as the
      first.
AB  - When two objects are presented in rapid succession, observers find it difficult
      to discriminate their temporal order. Below certain limit (e.g., 20-70 ms), the
      rate of correct temporal order judgement is reported to be about 50% (i.e., close
      to chance level). However we have found stimulus conditions where order
      discrimination drops significantly below chance level: the stimulus that is
      presented as the second is reported as the first. It is necessary that the
      stimuli are very brief, spatially overlapping, clear-cut backward and forward
      masking is absent, stimulus onset asynchronies are very short, and luminance
      contrast of the following stimulus is considerably lower than luminance contrast
      of the first stimulus. The higher the contrast ratio, the stronger the order
      reversal effect. However, because also in the conditions where the two stimuli
      are presented synchronously, the dimmer target is perceived as the first, the
      effect should be attributed to some implicit bias which enforces subjects to
      regard a more contrasted stimulus as the one that appears subsequent to the less
      contrasted stimulus.

PMID- 14642897
TI  - Uptake and esterification of vitamin A by RCS rat retinal pigment epithelial
      cells in primary culture.
AB  - We investigated the capacity of Royal College of Surgeons (RCS) rat retinal
      pigment epithelial (RPE) cells to take up all-trans-retinol (ROL) (vitamin A) and
      to metabolize it into retinyl esters (RE). Cultures of RPE cells were established
      from RCS and control newborn rats. All-trans-ROL was delivered to the apical
      surface of the RPE monolayer. Retinoids were analyzed by high-performance liquid
      chromatography. The cellular retinol-binding protein type I (CRBP-I) was assessed
      by Western blotting. Before supplementation with ROL, RE were lower in RCS rats.
      After ROL supplementation, esters increased and reached values that were similar
      in the two strains, but the increase, expressed relative to the initial value,
      was higher in RCS rats. The uptake of ROL and the level of CRBP-I were greater in
      RCS rats. Our results provide evidence of a functional retinol esterifying enzyme
      in cultured RCS RPE cells and suggest that CRBP-I could play a role in the uptake
      and esterification of ROL in the RPE cells.

PMID- 14642898
TI  - Sensitivity to curvatures in orientation-based texture segmentation.
AB  - Texture segregation has long been attributed to changes in the distribution of
      elementary features across the visual field [Nature 290 (12) (1981) 91; Biol.
      Cybernet. 54 (1986) 245]. The study of orientation, a conspicuous feature, has
      led to models of orientation-based texture segmentation (OBTS) that depend on the
      magnitude of one or two orientation gradients [Vis. Res. 31 (4) (1991) 679; Vis.
      Res. 31 (6) (1991) 1073] and influenced further by the relative configuration
      between the orientation textons and the global orientation edge [Percept.
      Psychophys. 52 (4) (1992) 255; Vis. Res. 35 (20) (1995) 2863]. Here we show that
      these models are at best partial and that the notion of orientation gradient has
      been incompletely used in the study of OBTS. To do so, we first study the
      behavior of orientation in orientation-defined texture patches. Geometrical
      analysis identifies two texture curvatures and reveals the incompleteness of
      previous stimuli. Psychophysical experimentation then demonstrates that
      segmentation is strongly affected by discontinuities in these curvatures.
      Importantly, we show that this sensitivity to curvature is independent of the
      orientation gradients and inconsistent with the simple configural considerations
      proposed in the past.

PMID- 14642899
TI  - Pulling the other one: 1st- and 2nd-order visual information interact to
      determine perceived location.
AB  - We demonstrate that the 1st- and 2nd-order characteristics of a visual stimulus
      can have a profound influence on each other in terms of perceived position. We
      use the parameter of spatial separation to selectively manipulate the effect of
      one characteristic upon the other. 1st-order features have their largest effect
      upon the perceived position of 2nd-order structure when separation is small,
      whilst the reciprocal effect is maximal at large separations. Implications for
      models of 1st- and 2nd-order interaction are discussed.

PMID- 14642900
TI  - In search of an elusive hard threshold: a test of observer's ability to order sub
      threshold stimuli.
AB  - The contrast transducer function (d' vs. contrast) for sine gratings was claimed
      to come up from some non-zero contrast value rather than from the origin. This
      implies that there is a point (a hard threshold) on the grating contrast axis
      below which observers could not distinguish between presentations containing
      gratings and those containing a homogeneous field. We studied the ability to
      order sub-threshold square wave gratings and found, to the contrary, that
      observers were able to do this no matter how low the contrasts. At the same time,
      the observers failed to order the sub-threshold gratings when they were of the
      same contrast. The latter is inconsistent with signal detection theory which
      predicts that an observer's judgements are based on the same ordered set of
      sensory states irrespective of whether the stimuli differ or are the same. On the
      other hand, these data can be reconciled with the notion of a threshold if the
      latter is thought of as a fuzzy rather than a sharp margin on the contrast axis.

PMID- 14642901
TI  - Illusory surfaces affect the integration of local motion signals.
AB  - A 2IFC paradigm was used to measure speed discrimination thresholds for pairs of
      Gabor patches. When one of these patches was phenomenally placed over an illusory
      surface (IS), we observed higher thresholds relative to control conditions
      without ISs. Additional controls demonstrated that this effect was due to the
      placement of the patch on a different phenomenal depth plane rather than to the
      mere presence of an IS. We conclude that (i) ISs can affect the long-range
      integration of local motion signals, and (ii) long-range motion integration obeys
      a coplanarity principle.

PMID- 14642902
TI  - Brightness assimilation in bullseye displays.
AB  - In simultaneous brightness contrast displays, a gray target square G(B) bordered
      by black appears brighter than an identical gray target square G(W) bordered by
      white. Here we demonstrate that this effect can be reversed if G(B) is surrounded
      by bands that alternate outward from black to white, while G(W) is surrounded by
      bands that alternate outward from white to black. With these simple "bullseye"
      displays assimilation generally occurs--G(B) appears darker than G(W).
      Experiments 1 and 2 used a 2AFC design with a 2.2 s display duration. The results
      of these experiments indicate that (i) substantial assimilation occurs for target
      Weber contrasts (relative to the gray background) of -0.25, 0, and 0.25, but
      assimilation was maximal when target contrast was -0.25 and decreased as target
      contrast increased, (ii) assimilation effects were the same whether the width of
      the four surround bands was 20% of the target or 40% of the target, and (iii)
      assimilation occurs with as few as 2 surround-bands and the magnitude of the
      effect increases slightly as the number of bands increase. When experiment 1 was
      re-run using the method of matching (experiment 3), however, the results changed
      dramatically: (moderate) assimilation effects were found only when target
      contrast was -0.25; when target contrast was 0.25, there was a brightness
      contrast effect; when target contrast was 0, there was no illusion. Assimilation
      effects in bullseye displays are not predicted by the CSF model described in
      DeValois and DeValois [Spatial Vision, Oxford University Press, New York, 1988],
      the anchoring model of Gilchrist et al. [Psychological Review, 106(4) (1999)
      795], or Blakeslee and McCourt's [Vision Research 39 (1999) 4361] ODOG model. We
      propose that this assimilation effect is the result of a contrast inhibition
      mechanism similar to that proposed by Chubb et al. [Proceedings for the National
      Academy of Science, vol. 86, 1989, p. 9631] to underlie contrast effects.

PMID- 14642903
TI  - Eye movements in reading isolated words: evidence for strong biases towards the
      center of the screen.
AB  - Three experiments were conducted that compared the eye movement pattern to a
      peripheral word or letter string as a function of the position of an initial
      fixation stimulus relative to the center of the screen and the straight-ahead
      position. Results revealed a strong bias of the eye behavior towards the center
      of the screen, but not towards the straight-ahead position. Saccades were greater
      in length, and landed closer to the center of words/strings when launched from a
      position left of center than when launched from either center or right part of
      the screen. In addition, the initial saccade launch site was deviated to the
      right, or to the left of the initial fixation stimulus depending on where
      relative to the center of the screen the fixation stimulus was displayed. Data
      were interpreted with the assumption that saccades are programmed in a visual
      reference framework, with saccade amplitude being computed in relative
      coordinates. Further research will determine whether the observed bias
      generalizes to text reading.

PMID- 14642904
TI  - Electrochemistry of nano-scale bacterial surface protein layers on gold.
AB  - The mechanism of the recrystallization of nano-scale bacterial surface protein
      layers (S-layers) on solid substrates is of fundamental interest in the
      understanding and engineering of biomembranes and e.g. biosensors. In this
      context, the influence of the charging state of the substrate had to be
      clarified. Therefore, the electrochemical behaviour of the S-layers on gold
      electrodes has been investigated by in-situ electrochemical quartz microbalance
      (EQMB) measurements, scanning force microscopy (SFM) and small-spot X-ray
      photoelectron spectroscopy (SS-XPS) of potentiostatically emersed substrates. It
      was shown that the negatively charged bonding sites of the S-layer units (e.g.
      carboxylates) can bond with positively charged Au surface atoms in the positively
      charged electrochemical double layer region positive of the point of zero charge
      ( approximately -0.8 V vs. saturated mercury-mercurous sulphate electrode).
      Surface conditions in other potential regions decelerated the recrystallization
      and fixation of S-layers. Time-resolved in-situ and ex-situ measurements
      demonstrated that two-dimensional S-layer crystal formation on gold electrodes
      can occur within few minutes in contrast to hours common in self-assembled
      monolayer (SAM) generation. These results proved that the recrystallization and
      fixation of 2D-crystalline S-layers on an electronic conductor can be influenced
      and controlled by direct electrochemical manipulation.

PMID- 14642905
TI  - Electrical breakdown of human erythrocytes: a technique for the study of electro
      haemolysis.
AB  - This paper describes a technique suitable for investigating the electromechanical
      breakdown properties of erythrocyte cells. The cells were exposed to square wave
      electric pulses of precise duration and voltage. The erythrocytes were suspended
      in normal isotonic saline between two opposing platinum electrodes. A red LED
      light source and photodiode detector system were positioned orthogonally to the
      electrodes to record changes in the light transmission that occur immediately
      after applying an electric pulse. The light transmitted through the electrically
      treated erythrocyte suspension could be monitored continuously. Experiments were
      conducted to explore the inter-relationship between the critical voltage and
      pulse length for haemolysis. Human blood taken from "healthy" donors underwent
      haemolysis at a critical field strength of 304 kV/m for a 5 micros pulse and 292
      kV/m for a 50 micros pulse. The relationship of critical pulse length and
      critical voltage for the blood samples was found to be inversely linear.

PMID- 14642906
TI  - Impedance analysis of phosphatidylcholine membranes modified with gramicidin D.
AB  - Electrochemical impedance spectroscopy (EIS) was used to the study of gramicidin
      D (GD) dimerization and to transport of monovalent cations across lipid bilayers
      by the dimers. Phosphatidylcholine (PC) membranes were studied, unmodified and
      modified with very low GD concentrations in the presence of various potassium ion
      concentrations. A new method was proposed to determine the parameters used to
      describe the gramicidin dimer: gramicidin surface concentration (c(GG)), area
      occupied by individual channel (A(G)) and gramicidin dimerization equilibrium
      constant (K(GG)). It was shown that electrochemical impedance spectroscopy
      measurements of lipid bilayer membranes yielded the K(GG) and A(G) values of the
      same order of magnitude as other measurement techniques.

PMID- 14642907
TI  - Electrochemical and electrocatalytic properties of myoglobin and hemoglobin
      incorporated in carboxymethyl cellulose films.
AB  - Protein-CMC films were made by casting a solution of myoglobin (Mb) or hemoglobin
      (Hb) and carboxymethyl cellulose (CMC) on pyrolytic graphite electrodes. In pH
      7.0 buffers, Mb and Hb incorporated in CMC films gave a pair of well-defined and
      quasi-reversible cyclic voltammetric peaks at about -0.34 V vs. SCE,
      respectively, characteristic of heme Fe(III)/Fe(II) redox couples of the
      proteins. The electrochemical parameters such as apparent standard heterogeneous
      electron transfer rate constants (k(s)) and formal potentials (E degrees ') were
      estimated by square wave voltammetry with nonlinear regression analysis. In
      aqueous solution, stable CMC films absorbed large amounts of water and formed
      hydrogel. Scanning electron microscopy of the films showed that interaction
      between Mb or Hb and CMC would make the morphology of dry protein-CMC films
      different from the CMC films alone. Positions of Soret absorbance band suggest
      that Mb and Hb in CMC films retain their secondary structure similar to the
      native states in the medium pH range. Trichloroacetic acid, nitrite, oxygen, and
      hydrogen peroxide were catalytically reduced at protein-CMC film electrodes.

PMID- 14642908
TI  - Investigation of electrochemical properties of FMN and FAD adsorbed on titanium
      electrode.
AB  - The electrochemical properties (such as the values of the formal potentials, the
      dependence of the formal potentials on solution pH, the reversibility of the
      electrochemical process) of flavin mononucleotide (FMN) and flavin adenine
      dinucleotide (FAD) adsorbed on a titanium electrode were dependent on the
      electrolyte. The formal potentials of adsorbed FMN and FAD in phosphate, HEPES
      and PIPES buffers at pH 7 were similar to those for dissolved flavins (-460 to 
      480 mV vs. SCE) and changed linearly with a slope of about 52 mV per pH unit in
      the pH region 3 to 8. In TRIS buffer, the formal potentials of adsorbed FMN and
      FAD were also pH-dependent, however, with invariance in the pH range 4.5 to 5.5.
      In non-buffered solutions (KCl, LiCl, NaCl, CsCl, CaCl(2), Na(2)SO(4) at
      different concentrations), the electrochemical behavior of adsorbed FMN and FAD
      differed from that of dissolved flavins and was dependent on the electrolyte
      (especially at pH 4.5 and pH 5). Under certain conditions (electrolyte,
      concentration, pH), a two-step oxidation of FMN could be observed.

PMID- 14642909
TI  - Studies on electrochemical properties and scavenge of superoxide anion in aprotic
      media by using carbon nanotubes powder microelectrode.
AB  - Multiwall carbon nanotubes (MWCNTs) are filled in the cavity at the tip of a
      microelectrode to form a carbon nanotubes powder microelectrode (CNTs-PME). CNTs
      PME was used to study electrochemical properties of superoxide anion in aprotic
      media. The reversibility of the oxygen/superoxide anion couple (O(2)/O(2)(.-)) at
      the different powder microelectrode in different aprotic media was compared by
      cyclic voltammetry (CV). The result indicated that the nearly reversible redox
      process of the O(2)/O(2)(.-) couple was obtained at a CNTs-PME. The heterogeneous
      electron transfer rate constant (k(s)) can be measured by steady-state
      voltammogram and the result is 4.7 x 10(-3) cm s(-1), suggesting that the
      electrode reaction is a nearly reversible process as expected. The scavenging
      activities of bilirubin, alpha-tocopherol (vitamin E), are examined, and the
      experimental results confirm that alpha-tocopherol is the better scavenger toward
      O(2)(.-) between them.

PMID- 14642910
TI  - Sequential-injection stripping analysis of nifuroxime using DNA-modified glassy
      carbon electrodes.
AB  - The voltammetric behavior of nifuroxime was investigated comparing stationary
      voltammetric methods with the recently proposed sequential-injection stripping
      analysis (SISA), by using cyclic voltammetry (CV) and differential-pulse
      voltammetry at bare and DNA-modified glassy carbon (GC) electrodes. In cyclic
      voltammetry, reduction of nifuroxime at DNA-modified electrodes gives rise to a
      well-defined peak, and in contrast to bare GC surfaces, a re-oxidation peak could
      be observed. Optimization of the pre-concentration process at the DNA-modified
      surface led to a significant enhancement of the voltammetric current response, a
      better defined peak shape and an improved dynamic range. Based on this optimized
      voltammetric procedure, SISA has been evaluated for the determination of
      nifuroxime. The flow-system significantly facilitates the regeneration of the DNA
      modified electrode surface, hence diminishing problems related to accumulation
      and memory effects. The linear detection range could be extended to 65 microM
      with a detection limit (3 s) of 0.68 microM, which corresponds to an absolute
      amount of 21 ng nifuroxime.

PMID- 14642911
TI  - Sub-microsecond, intense pulsed electric field applications to cells show
      specificity of effects.
AB  - Application of sub-microsecond duration (60-300 ns), intense (15-60 kV/cm) pulsed
      electric fields (sm/i-PEF) to six types of human cells was examined for its
      effects on individual cell surface membrane permeability and membrane potential.
      With short (60 ns) pulses, increasing percentages of Jurkat cells showed
      propidium iodide (PI) uptake at progressively shorter post-pulse times as the
      pulse train increased from 1 to 10 sequential pulses, while human blood
      polymorphonuclear leukocytes (PMN) were unresponsive to these short pulses
      regardless of train size. With 300 ns pulses, a similar pattern (increasing
      percentages of cells taking up PI, and progressively shorter times of onset after
      pulse applications as pulse train size increased) was seen with both Jurkat cells
      and PMN, but the patterns for both effects were different. Jurkat cell size did
      not appear to influence the responsiveness of this cell type. Comparisons of sm/i
      PEF-induced PI uptake by human monocyte-derived macrophages vs. aged human
      mononuclear cells, human trunk skin (HTS) cells vs. fresh human mononuclear cells
      and human macrophages vs. HTS cells showed similar overall effects, but with
      differences between the patterns for each cell type compared (except the
      macrophages vs. HTS cells comparison). Application of sm/i-PEFs also caused
      different patterns of membrane potential loss in Jurkat cells vs. PMN. Jurkat
      cells developed significant decreases in t heir membrane potential only following
      the highest intensity pulse applications examined, i.e., 300 ns, 60 kV/cm x5,
      while PMN showed this effect over the entire range of pulse intensities (300 ns,
      15-60 kV/cm, x5) applied. These data indicate that sm/i-PEF applications can have
      "specificity" (i.e., achieve different levels of effect in different cell types),
      that cell size does not appear to be the major factor determining sm/i-PEF
      effects in either Jurkat cells or PMN, that heterogeneous sm/i-PEF effects on
      cells tend to become homogeneous with increasing pulse train size, and that
      specificity of sm/i-PEF applications effects can occur at either end of the sm/i
      PEF intensity spectrum examined.

PMID- 14642912
TI  - Energetics and mechanisms of high efficiency of charge separation and electron
      transfer processes in Rhodobacter sphaeroides reaction centers.
AB  - Effects of environmental changes due to D(2)O/H(2)O substitution and cryosolvent
      addition on the energetics of the special pair and the rate constants of forward
      and back electron transfer reactions in the picosecond-nanosecond time domain
      have been studied in isolated reaction centers (RC) of the anaxogenic purple
      bacterium Rhodobacter sphaeroides. The following results were obtained: (i).
      replacement of H(2)O by D(2)O or addition of either 70% (v/v) glycerol or 35%
      (v/v) DMSO do not influence the absorption spectra; (ii). in marked contrast to
      this invariance of absorption, the maxima of fluorescence spectra are red shifted
      relative to control by 3.5, 6.8 and 14.5 nm for RCs suspended in glycerol, D(2)O
      or DMSO, respectively; (iii). D(2)O/H(2)O substitution or DMSO addition give rise
      to an increase of the time constants of charge separation (tau(e)), and Q(A)(-)
      formation (tau(Q)) by a factors of 2.5-3.1 and 1.7-2.5, respectively; (iv).
      addition of 70% glycerol is virtually without effect on the values of tau(e) and
      tau(Q); (v). the midpoint potential E(m) of P/P(+) is shifted by about 30 and 45
      mV towards higher values by addition of 70% glycerol and 35% DMSO, respectively,
      but remains invariant to D(2)O/H(2)O exchange; and (vi). an additional fast
      component with tau(1)=0.5-0.8 ns in the kinetics of charge recombination
      P(+)H(A)(-)-->P*(P)H(A) emerges in RC suspensions modified either by D(2)O/H(2)O
      substitution or by DMSO treatment. The results have been analysed with special
      emphasis on the role of deformations of hydrogen bonds for the solvation
      mechanism of nonequilibrium states of cofactors. Reorientation of hydrogen bonds
      provides the major contribution of the very fast environmental response to
      excitation of the special pair P. The Gibbs standard free energy gap between 1P*
      and P(+)B(A)(-) due to solvation is estimated to be approximately 70, 59 and 48
      meV for control, D(2)O- and DMSO-treated RC samples, respectively.

PMID- 14642913
TI  - Monitoring of water content and water distribution in ischemic hearts.
AB  - We determined water content and water distribution by fitting dielectric spectra
      of ischemic canine hearts between 5 MHz and 3 GHz with a newly developed model
      which describes heart cells and subcellular organelles as rotational ellipsoids
      filled with electrolyte enclosed by an isolating membrane. The fraction of dry
      material is modelled by spherical particles with a small dielectric permittivity.
      Free model parameters were water content, cell volume fraction, and the
      conductivity of the electrolytes. Resulting model parameters were compared to
      data from tissue desiccation and to conductivity changes produced by protons and
      lactate ions. We investigated hearts in two states: during ischemia after
      interruption of blood flow (pure ischemia, PI, n=5) and during ischemia after
      resuscitation with Tyrode's solution (IAR, n=14). The difference between water
      content determined by tissue desiccation and by dielectric spectroscopy was less
      than 0.5%. During 360 min of ischemia, water content in IAR decreased from 85+/
      1.6% to 83+/-2.2% and in PI from 80+/-0.8% to 78+/-1.5%. Cellular volume fraction
      in IAR increased from 0.47+/-0.045 to 0.63+/-0.031 and in PI from 0.62+/-0.014 to
      0.73+/-0.013, which is consistent with published morphometric data. After 180 min
      of ischemia, the increase of the cytosolic conductivity was 0.14+/-0.02 S/m as
      calculated from the dielectric spectrum and was similar to the conductivity
      increase which was roughly estimated on the basis of tissue lactate
      concentration. In conclusion, dielectric spectroscopy combined with our model
      analysis facilitates the monitoring of water content and distribution by means of
      nondestructive surface probes.

PMID- 14642914
TI  - Electromagnetic acceleration of the Belousov-Zhabotinski reaction.
AB  - Acceleration of the Belousov-Zhabotinski (BZ) reaction, in stirred homogeneous
      solutions, by low frequency electromagnetic (EM) fields has provided new insights
      into EM interaction mechanisms. The acceleration varies inversely with the basal
      reaction rate, indicating that the applied magnetic field and the intrinsic
      chemical driving forces affect the same electron transfer reaction. The amplitude
      and frequency dependence of the EM field interactions are also consistent with
      interaction during electron transfer. A mechanism based on interaction with
      moving electrons offers a way of explaining the ability of EM fields to stimulate
      gene expression, in particular the stress response, since electrons have been
      shown to move in DNA.

PMID- 14642918
TI  - Adolescent oncology--a homeland for the "lost tribe".

PMID- 14642915
TI  - Theoretical analysis of the thermal effects during in vivo tissue
      electroporation.
AB  - Tissue electroporation is a technique that facilitates the introduction of
      molecules into cells by applying a series of short electric pulses to specific
      areas of the body. These pulses temporarily increase the permeability of the cell
      membrane to small drugs and macromolecules. The goal of this paper is to provide
      information on the thermal effects of these electric pulses for consideration
      when designing electroporation protocols. The parameters investigated include
      electrode geometry, blood flow, metabolic heat generation, pulse frequency, and
      heat dissipation through the electrodes. Basic finite-element models were created
      in order to gain insight and weigh the importance of each parameter. The results
      suggest that for plate electrodes, the energy from the pulse may be used to
      adequately estimate the heating in the tissue. However, for needle electrodes,
      the geometry, i.e. spacing and diameter, and pulse frequency are critical when
      determining the thermal distribution in the tissue.

PMID- 14642919
TI  - Where should teenagers with cancer be treated?
AB  - Cancer in teenagers is relatively uncommon. Few health professionals in oncology
      are familiar with caring for teenagers, although most would acknowledge them as a
      characterisable clientele with specific needs different to those of others with
      cancer, whether younger or older. Many of those diagnosed with cancer between 13
      and 20 years of age will be cured, often after intensive, toxic and life-changing
      treatment. The provision of the highly specialised medical and nursing care
      needed for cancer treatment must go alongside meeting the specific needs
      associated with this age group, an age of transition from childhood to adulthood.
      Care provision for teenagers must therefore address the treatment, information,
      educational, social and other support requirements of teenagers and their
      families. This must be done through the work of a highly specialised, experienced
      multidisciplinary team. A dedicated Teenage Cancer Unit (TCU) provides an
      appropriate environment in which teenagers may feel comfortable and from which
      such a multidisciplinary team can function. Such units cannot provide every
      aspect of a teenager's care throughout their cancer journey so must work in
      harmony with other agencies, particularly those in the community. TCUs are most
      successful when they are of sufficient size to ensure a critical mass of staff
      and experience. Not all teenagers with cancer will be treated on a TCU and other
      models that can meet both medical and age-specific needs are required.

PMID- 14642920
TI  - Who should be treating adolescents and young adults with acute lymphoblastic
      leukaemia?
AB  - Although several cancers have a peak incidence during adolescence and young
      adulthood, the patients in this age group are arbitrarily referred to either
      paediatric or adult oncologists and, consequently, treated on different
      protocols. Recent reports show that paediatric oncologists are more likely to
      enroll patients in clinical trials, and that adolescents who are treated on
      paediatric protocols have a better outcome than their counterparts who are
      managed by adult oncologists. These observations were also noted in adolescents
      with acute lymphoblastic leukaemia (ALL), a disease with a bimodal peak incidence
      in early childhood and late adulthood. Recently, investigators have become aware
      that patients in the adolescent and young adult age group might be falling
      through the cracks because of the rigid organisation of the medical care system.
      In this article, I present some of the current challenges in the treatment of ALL
      in adolescents and young adults and propose strategies to improve outcome in
      these patients.

PMID- 14642921
TI  - The management of cancer in the older adolescent.
AB  - Cancer in adolescents 15-19 years of age occurs at nearly twice the rate observed
      in 5- to 14-year-olds, but as of yet they have no explicit organisation for
      research and care, such as that structured for younger paediatric patients.
      Adolescents with cancer must be recognised as a subgroup of oncology patients
      with specific characteristics and needs requiring dedicated interest and
      management. The need is made most evident as outcome data indicates that
      adolescents are lagging behind in survival gains made in recent decades by both
      children and adults with cancer. Improvements in the overall survival, quality of
      care and quality of survival of adolescents with cancer will only occur by
      surmounting the challenges, discussed in this review, unique to this group of
      patients.

PMID- 14642922
TI  - Cancer survival in European adolescents and young adults.
AB  - Survival of patients aged 15-24 years, diagnosed with cancer during the period of
      1990-1994, is described within Europe. Data on 15101 patients, extracted from the
      files of the 56 adult cancer registries included in the EUROCARE-3 database,
      representing 20 European countries, were analysed and compared. Five-year
      survival for 'all cancers combined' was 75% in males (ranging from 59% in Estonia
      to 89% in Iceland), and 78% in females (ranging from 59% in Estonia to 89% in
      Norway). The Northern European countries (except Denmark) and Austria had the
      highest survival figures, while survival in the Eastern European countries was
      lower than the European average. Denmark, UK, and the pool of the central
      European countries, had intermediate survival figures. Haemopoietic tumours were
      the most common malignancies: 5-year survival was high for Hodgkin's disease
      (89%), intermediate for non-Hodgkin's lymphoma (68%) and lower for acute
      lymphoblastic leukaemia (ALL) (47%) and acute myeloblastic leukaemia (AML) (39%).
      Five-year survival for gonadal germ cell cancers, the second most common
      malignancy in young adults, was 90%. Five-year survival for the other cancers
      under consideration was as follows: 89% for skin melanoma, 66% for all Central
      Nervous System (CNS) tumours, 57% for bone tumours, 58% for osteosarcoma, 42% for
      Ewing's sarcoma, 57% for soft-tissue sarcomas, 99% for thyroid carcinoma, 82% for
      uterine cervical carcinoma, and 83% for ovarian carcinoma. For more 'adult
      specific tumours', 5-year survival was good for colon (77%) and lung (60%)
      cancers, and less favourable, compared with adults, for breast cancer (68%).
      Adolescents (15-19 years) had significantly worse survival than young adults (20
      24 years) for all malignancies combined. Survival for Hodgkin's lymphoma, CNS
      tumours, melanoma and colon cancer showed marked regional variability. Since many
      of the tumours occurring in young adults are curable, these results should
      encourage, without delay, efforts to identify obstacles to improving outcome and
      reducing geographical inequalities in survival for this group of patients.

PMID- 14642923
TI  - Trends in cancer mortality at age 15 to 24 years in Europe.
AB  - Trends in death certification rates from all cancers and seven selected cancer
      sites (bone sarcoma, soft-tissue sarcoma, ovary, testis, non-Hodgkin's lymphomas,
      Hodgkin's disease, leukaemias) were analysed for the population aged 15-24 years
      in Europe and, for comparative purposes, in the United States of America (USA)
      and Japan over the period of 1965-1998. Overall, there was a decrease in total
      cancer mortality of approximately 40% for both sexes. The declined mortality is
      largely attributable to better treatments and inclusion in multicentre clinical
      trials. The degree of improvement was similar in Japan and the USA, but was less
      in Eastern European countries, reflecting delays in the application of effective
      treatments, and limited involvement in large, well-designed clinical trials for
      these curable cancers in Eastern Europe.

PMID- 14642924
TI  - Incidence of malignant disease by morphological type, in young persons aged 12-24
      years in England, 1979-1997.
AB  - Cancer incidence data are generally presented in terms of primary site, but this
      method is inappropriate for cancers in young persons. We have used a morphology
      based classification system to produce national incidence rates for cancers in
      persons aged 12-24 years by detailed diagnostic sub-type. The overall incidence
      rates for malignant disease in young persons aged 12-14, 15-19 and 20-24 years
      were 10.1, 14.4 and 22.6 per 100000 population, respectively. The three most
      frequent cancer types in 12-14-year-olds were leukaemias, lymphomas and central
      nervous system (CNS) tumours. In 15-19-year-olds, lymphomas were most frequent
      and leukaemias second with carcinomas third. In 20-24-year-olds, lymphomas were
      again most frequent, but carcinomas and germ cell tumours were second and third.
      There was also variation with age in the ratios of rates in males and females.
      These changing incidence patterns have aetiological implications and provide
      clues for future hypothesis-based research.

PMID- 14642925
TI  - Breast cancer in adolescents and young women.
AB  - Breast cancer is very rare in adolescents and very young women. Less than 1% of
      all breast cancer cases occur before the age of 30 years (Natl Cancer Inst Monogr
      16 (1994) 69). Invasive breast cancer occurring in women before the age of 35
      years has a more aggressive biological behaviour and is associated with a worse
      prognosis than in older premenopausal women. Breast cancers in these young women
      are more frequently poorly differentiated, oestrogen-receptor (ER)-negative, have
      lymphovascular invasion and high proliferating fractions. Breast-conserving
      surgery in women <35 years old is associated with a higher risk of local
      recurrence than in older women. All young women should be considered at moderate
      high risk by virtue of their age alone and offered adjuvant therapy. The long
      term toxicity of adjuvant therapies is a particular concern when treating these
      women. The implications of possible fertility impairment and premature menopause
      require consideration when discussing adjuvant chemotherapy and endocrine
      therapy. Adolescents and young women are particularly vulnerable to emotional
      distress and psychosocial problems and should be provided with appropriate
      support. Young women who are at a potential high-risk of developing breast cancer
      such as those with germline mutations of BRCA1, BRCA2, TP53, PTEN or who have
      previously received mantle irradiation for Hodgkin's disease need close follow-up
      and are candidates for screening from a young age.

PMID- 14642926
TI  - Central nervous system tumours in adolescents.
AB  - Adolescents with brain tumours have been, and in most cases still are,
      haphazardly assigned, on referral, to either 'paediatric' or 'adult'-based
      treatment centres. In this age group, there is therefore a history of
      inconsistent treatment, delivery of inappropriate 'maturity-related' care and a
      reduced chance of gathering vital biological, clinical and treatment-related
      information germane to this group of patients and their tumours. These days,
      adolescents with brain tumours should be actively targeted for recruitment into
      clinical trials and admission into dedicated neuro-oncology centres or programmes
      that can deliver the necessary and age appropriate multidisciplinary management.

PMID- 14642927
TI  - Melanoma in children and adolescents.
AB  - Childhood and adolescent melanoma is rare, accounting for only 1.3% for all cases
      of cancer in patients under the age of 20 years. However, in 15-19 year olds,
      melanoma accounts for up to 7% of all cancers. Review of reported cases in this
      age group reveals that predisposing 'paediatric' conditions such as a giant
      congenital melanocytic naevi or xeroderma pigmentosum are rarely present.
      Furthermore, inactivating germ-line mutations of the gene CDKN2A have only been
      reported in 1.5% of cases of early onset melanoma. Epidemiological studies
      suggest that interactions between solar exposure, development of naevi,
      pigmentary traits, and a family history of melanoma are the main determinants of
      melanoma development during the first 20 years of life. As yet, there are no
      available staging or treatment strategies for this group of patients so treatment
      recommendations are based on the adult experience. To improve our understanding
      of the natural history of melanoma and to identify the most appropriate therapies
      for young patients with this disease, practising physicians are encouraged to
      enroll their patients, especially those with advanced stage disease, in
      cooperative group trials which incorporate newer staging systems and promising
      therapies.

PMID- 14642928
TI  - Palliative care in adolescents.
AB  - Specialist Palliative Care's involvement in adolescent cancer is relatively new.
      The challenges are not so much to do with the technicalities of symptom control,
      but in walking the fine line with patients and families as they wrestle with
      transitions into an adulthood that will not happen and attempts to pack a lost
      future into a few months or years whilst coping with arduous and often futile
      treatments that attempt to buy some more time. The article explores some
      underlying principles and the model of care that has emerged at this specialist
      centre for adolescent care.

PMID- 14642929
TI  - Douglas House: a 'respice' for young people.

PMID- 14642930
TI  - Fatigue in adolescents with and following a cancer diagnosis: developing an
      evidence base for practice.
AB  - Although fatigue has been a focus for research in adult cancer care for some
      time, the same cannot be said for adolescent oncology practice. This paper
      summarises the literature concerning fatigue in adolescents with, and following,
      cancer diagnoses, drawing on data from four empirical studies. Fatigue is
      multidimensional, multifactorial and highly subjective, but can be managed to
      enhance self-caring and coping strategies. All of the studies reviewed within
      indicate that fatigue is a troublesome symptom, which impacts on quality of life.
      From this review, we set up a research study. This paper provides a brief report
      of preliminary data from this study drawn from a group of adolescents in late
      remission from childhood cancer. These data are used to evaluate the utility of
      focus groups as a method of data collection in exploring the concept of fatigue
      in adolescents. Concurring with the studies we reviewed, findings from the
      preliminary data suggest that fatigue is a highly subjective and 'abnormal'
      phenomenon that holds a variety of implied meanings and associated metaphors
      connected with past experiences of childhood cancer. The focus group proved to be
      a viable research method to facilitate mutual disclosure and provoke discussion.
      Recognition of the research challenges with adolescents, where there is the
      potential for a range of meanings for the experience of fatigue, is an important
      finding for future studies.

PMID- 14642931
TI  - The benefits and drawbacks of treatment in a specialist Teenage Unit--a patient's
      perspective.

PMID- 14642932
TI  - Bridging the gaps: transition for young people with cancer.

PMID- 14642933
TI  - The Teenage Cancer Trust--advocating a model for teenage cancer services.

PMID- 14642935
TI  - [The new program for residents in obstetrics and gynecology: implications for
      training and practice of our future specialists?].

PMID- 14642936
TI  - [Oocytes in vitro maturation: results and future in humans].
AB  - Mature oocytes are rare and highly specialized cells. In vitro maturation of
      human oocytes is an emerging assisted reproductive technology allowing to produce
      more mature oocytes without ovarian stimulation. Whereas in vitro maturation is
      technically more demanding than conventional in vitro fertilization for the
      laboratory, it carries many potential advantages, for example, in terms of lower
      treatment heaviness and removal of risk of severe ovarian hyperstimulation
      syndrome for the patients. Although the technology is still experimental, oocytes
      in vitro maturation has been successfully used and pregnancies and live births
      have been reported. Despite these successes, the overall efficiency of in vitro
      maturation remains low and this procedure must still be improved. The different
      steps of in vitro maturation process are shown and discussed as well as results
      in terms of pregnancy and live birth rates.

PMID- 14642937
TI  - [Clinical management of non palpable breast lesions: experience about a series of
      176 consecutive cases].
AB  - OBJECTIVE: To propose a rational attitude to treat infraclinic breast lesions
      about a 176-case retrospective analysis. PATIENTS AND METHODS: Between January
      and December 2000, 176 patients were addressed for an infraclinic breast lesion.
      The epidemiologic and mammographic data, diagnostic management and histological
      results were collected. RESULTS: Patients were addressed for an ACR 2 lesion in
      0.8% of cases, ACR 3: 34.8%, ACR 4: 43.2% and ACR 5: 21.2%. One hundred and
      sixteen patients underwent a stereotactic macrobiopsy: 55 Advanced Breast Biopsy
      Instrumentation (ABBI), 61 Minimal Invasive Breast Biopsy (MIBB). Histologically,
      59.5% were benign, 33.6% malignant, 2.6% borderline and 4.3% suspicious or non
      contributive. Forty-two patients underwent an open surgical biopsy.
      Histologically 56.1% were benign, 41.5% malignant and 2.4% borderline. Eighteen
      patients were controlled by mammography. Among ACR 3s there were 90% of benign
      lesions and 46% of malignancy in ACR 4s. Patients with malignant, borderline or
      suspicious result in stereotactic biopsy, underwent one-time surgery in 97% vs
      55% in surgical biopsy (P < 0.0001). DISCUSSION AND CONCLUSION: Infraclinic
      breast lesions must be radiologically classified with the ACR classification.
      Stereotactic macrobiopsies are reserved for ACR 4 and ACR 5 lesions. Because of
      their reliability, practice of macrobiopsies avoids surgery in about 50% of ACR 4
      lesions which correspond to benign lesions. When the result is malignant, it
      allows most of times surgical procedure one-time.

PMID- 14642938
TI  - [Routine use of ST-segment of fetal electrocardiogram for monitoring labor. A
      year's experience (preliminary results)].
AB  - OBJECTIVES: Two randomized trials found that monitoring labor by analyzing the
      fetal electrocardiogram (STAN) appears to offer better sensitivity and
      specificity in screening for metabolic acidosis than cardiotocography (CTG) does.
      We report here the results of a descriptive study of 173 cases between 1 June
      2001 and 31 May 2002, the objectives of which were twofold: to determine the
      number of possible false negatives (defined by neonatal metabolic acidosis with a
      pH less than 7.05 and base deficit (BD) greater than 12 mmol/l, in the absence of
      a STAN decisions event more than 30 min before birth), and to assess whether STAN
      indicated the need for operative intervention too late in cases of fetal
      distress. PATIENTS AND METHODS: Our study was conducted on an at-risk population
      with CTG changes. STAN was used with a scalp electrode to monitor labor according
      to a protocol based upon the FIGO CTG classification and the clinical
      instructions used in the Swedish trial. Accordingly, we compared two groups: in
      group 1, a STAN decision event required a rapid conclusion to labor, while in
      group 2, the absence of any STAN decision event meant that labor continued,
      despite the changes in the tracing. RESULTS: We found seven cases with a neonatal
      pH less than 7.05, but only one may involve a false negative by this method. The
      mean arterial pH and the number of fetuses born with an arterial pH less than
      7.10 did not differ significantly between the two groups, nor were there any
      significant differences in the mean BD at birth, or the number of children with a
      BD greater than 12 mmol/l. CONCLUSION: The results appear to indicate that use of
      STAN with the usual CTG enables an appropriate response to cases of fetal
      distress, but it remains difficult to determine the real benefits that can be
      expected from this method in France. Longer assessment in our population is
      required before we can assess its actual advantages.

PMID- 14642939
TI  - [Towards a single embryo transfer: predictive value of uterine and embryological
      parameters in assisted reproduction outcome].
AB  - OBJECTIVE: The transfer of a single embryo would avoid obstetrical and neonatal
      complications due to multiple pregnancies. We studied the clinical value of both
      uterine and embryological parameters to define precise conditions allowing a
      single embryo transfer without decreasing pregnancy rates. PATIENTS AND METHODS:
      Endometrial parameters expressed by a uterine score together with biological
      criteria of 131 in vitro fertilization or intracytoplasmic sperm injection
      attempts were retrospectively analysed. RESULTS: Two hundred and sixty-two day-3
      embryos were replaced through 131 transfers. Fifty-seven pregnancies were induced
      and 16 twins were obtained. The clinical pregnancy rate was 35.9% and the
      embryonic implantation rate 24.0%. After the transfer of two embryos, successful
      implantation was determined by the occurrence of top-quality embryos and
      simultaneously by a receptive endometrium. The uterine pulsatility index was
      significantly decreased for twin compared to singleton pregnancies. DISCUSSION
      AND CONCLUSION: This study confirms that a uterine score constitutes a powerful
      tool for evaluating the uterine receptivity. This parameter has to be taken into
      account as well as the embryonic quality, in order to optimise the success rate.
      Young patients with at least two top-quality embryos available, a high uterine
      score and a low pulsatility index, have a high risk of multiple births and are
      suitable for a single-embryo transfer.

PMID- 14642940
TI  - [Pap test: liquid-based--thin-layer. A new method: results].
AB  - OBJECTIVES: Evaluation of the thin-layer technique we have developed. PATIENTS
      AND METHOD: An adequate shaking, a calibration and a centrifugation in liquid
      phase are the essential and specific stages of this technique. More than 160 000
      samples were prepared according to this methodology in eight years. RESULTS: The
      immediate profit of the technique is the increase of the number of interpretable
      samples: 99.9%. First years: net increase of the lesion detection rate in
      comparison with conventional cervical smear. 1.7 versus 0.9% for the low-grade
      lesions; 1.0 versus 0.4% for the high-grade lesions. After three years the
      detection rate of low-grade lesions remained high: 1.7% while the ASCUS/AGUS and
      high-grade lesions decreased to reach, respectively, 1.1 and 0.4%. DISCUSSION AND
      CONCLUSION: The quality of the thin-layer preparation, the best approach of the
      endocervical pathology, and the possibility to identify rare events, allowed us
      at first to increase detection of lesions. After three years of "picking up" of
      lesions forgotten by conventional cervical smear, the rate of high-grade lesions
      stabilised in 0.4%. Thus, it is advisable to take into account the notion of time
      as for the estimate of the lesion rate when using thin-layer technique compared
      with that of conventional cervical smear.

PMID- 14642942
TI  - [About two complications of ovarian drilling by fertiloscopy].
AB  - Two complications of ovarian drilling by fertiloscopy are described about two
      patients with polycystic ovary syndrome. Ovarian drilling by fertiloscopy is a
      new minimally invasive surgery, but this procedure is not without risks. It
      requires larger studies with longer follow-up to evaluate effectiveness and
      risks.

PMID- 14642941
TI  - [Endometrial ossification: about one case].
AB  - The ossification of the endometrium is a rare disease. The common feature in most
      reported cases is previous history of abortion with retention of foetal bones.
      However, the physiopathology is unknown. Clinical presentation may include
      secondary infertility as well as chronic inflammation of endometrium. About one
      recent observation and with help of publications, we will discuss
      physiopathology, symptomatology and therapeutics of this disease.

PMID- 14642943
TI  - [Sexual abuse: what gynaecologists hear].
AB  - For the last decade, it has become impossible for us to ignore the reality,
      frequency and psychopathological consequences of sexual abuses, even if those
      seldom constitute the official motive of patients' consultation. Many victims
      still hold to their secret. Hints such as behavior in our consultation rooms, way
      of expressing gynecological problems and certain sexual troubles should enable us
      to perceive their suffering. As for its cause, some patients, given enough time
      and empathy, will be able to open up and reveal it. It will take a long time as
      well as the help of other specialists to find the path towards repairing the
      damage.

PMID- 14642944
TI  - [Management of cervical intra-epithelial neoplasm during pregnancy].
AB  - Approximately 30% of women diagnosed with cervical cancer are in their
      childbearing years. Prenatal care provides an excellent opportunity for cervical
      cancer screening. The incidence of abnormal Pap smear has been reported in 5-8%
      of pregnant women. But we must know that Pap smears have cytologic modifications
      because of pregnancy. All abnormal smears have to be referred to colposcopic
      examination. The squamocolumnar junction is visualized in almost 100% of cases.
      The sensitivity of colposcopy is nearly 87% with complete concordance in 72.6%.
      Colposcopically directed biopsies have a good correlation with the final
      diagnosis with very minimal risks for both mother and fetus. The high rate of
      complications (hemorrhage, abortion, premature labor) and residual lesions in
      half of cases do not encourage conization during pregnancy. The final treatment
      is carried out after delivery. The only absolute indication for conization in
      pregnancy is to rule out microinvasive disease or make the diagnosis of invasive
      carcinoma when such a diagnosis will alter the timing of delivery but also when
      there is a no satisfactory colposcopy and a high-grade Pap smear. In these cases
      conization is performed for diagnostic and not therapeutic purpose. We must be
      aware of the high rate of loss of follow-up (6-33%).

PMID- 14642945
TI  - [Digital mammography].
AB  - Digital mammography is an irreversible evolution which will gradually replace
      analog mammography. Detector technology differs among manufacturers. Expected
      clinical advantages are improved diagnostic performances, improved
      reproducibility, dose reduction, dedicated applications (CAD), archiving and
      telemammography. Limiting problems are at cost, reorganization of the breast
      imaging unit and the medical workflow.

PMID- 14642946
TI  - [Tamoxifen, endometrial cancer and levonorgestrel intra-uterine device].
AB  - Although the adjuvant tamoxifen benefit/risk rate is unquestionable in breast
      cancer treatment, the increase of endometrial cancer in chemoprevention is about
      to be a real problem. In the studies currently published metrorragia in the main
      signal. Levonogestrel intra-uterine device has not proved its efficacy for the
      decrease of this risk.

PMID- 14642947
TI  - [A law to limit embryo transfer in ART?].

PMID- 14642948
TI  - [Thrombophilia and pregnancy. Prevention of thrombotic maternal and placental
      risks (March 2003)].

PMID- 14642949
TI  - [Can breast cancer be prevented by chemotherapy in 2003? Gynecol Obstet Fertil
      2003;31:327-336].

PMID- 14642950
TI  - [Can breast cancer be prevented by chemotherapy in 2003? Gynecol Obstet Fertil
      2003;31:327-336].

PMID- 14642951
TI  - [Problems raised by the gynaecologic management of women with BRCA 1 & 2
      mutations.Gynecol Obstet Fertil 2003;31:370-377].

PMID- 14642954
TI  - Endometriosis from thelarche to midteens: pathogenesis and prognosis, prevention
      and pedagogy.
AB  - John Huffman, a founder of the subspecialty of pediatric and adolescent
      gynecology in North America, first related the diagnosis of endometriosis to
      thelarche. Subsequently, endometriosis was diagnosed in early puberty between
      thelarche and menarche. Based on solid evidence, we suggest that the theory of
      embryonic mullerian rests be added to currently accepted theories of pathogenesis
      of endometriosis. This article argues for recognition of embryonic mullerian
      rests as the pathogenesis of some cases of endometriosis not explained by
      accepted theories. Along with Huffman, we propose that thelarche be recognized as
      a developmental benchmark, after which endometriosis is included in the
      differential diagnosis of chronic pelvic pain. Thus, in an effort to refocus
      research and patient care to early adolescence, this review is limited to
      endometriosis occurring in young women from thelarche to their sixteenth
      birthday. Relating endometriosis to thelarche has fundamental implications for
      pathogenesis, early diagnosis, prognosis, treatment, education, and long-term
      care of adolescents.

PMID- 14642955
TI  - Different shapes in different cultures: body dissatisfaction, overweight, and
      obesity in African-American and caucasian females.
AB  - OBJECTIVE: Body dissatisfaction and medical issues arising at both ends of the
      weight continuum are discussed from a cultural perspective. More specifically, a
      possible aesthetic preference and physical tolerance for increased adiposity
      among African-American females is discussed, as contrasted with that of Caucasian
      females. CONCLUSION: This mini-review of the existing literature suggests many
      avenues for future research in the cross-cultural aspects of body
      dissatisfaction, overweight, and obesity. Among these suggestions are (1)
      educating children and adolescents about excessive weight, (2) assessing cultural
      perceptions of overweight and obesity among African-Americans, (3) understanding
      the developmental trajectory of body dissatisfaction in females, and (4) placing
      more emphasis on the cross-cultural representation and psychological influence of
      the female body image in the media.

PMID- 14642956
TI  - Importance and knowledge of oral contraceptives in antepartum, low-income,
      African American adolescents.
AB  - STUDY OBJECTIVE: To assess motivation, sense of self-efficacy and knowledge of
      oral contraceptives (OC) in antepartum, African-American Adolescents and young
      adults following OC counseling. METHODS: Gravid African-American females, less
      than 25 years of age, receiving prenatal care at the Prentice Ambulatory Clinic
      at Northwestern Memorial Hospital were eligible for this study. Participants were
      enrolled after 34 weeks gestation, received one session of standardized OC
      counseling and then completed a series of questions regarding importance,
      confidence and knowledge of OCs. RESULTS: Forty-three adolescents and young
      adults participated in this study. Almost all participants agreed that it was
      important to plan their next pregnancy and to avoid unplanned pregnancies. On
      average, participants were extremely confident they could take a pill each day.
      Yet, while most were confident that they knew what to do if they missed one pill,
      only 37% actually knew what to do if they missed one pill. CONCLUSION: Despite
      high motivation and confidence in their ability to take OCs following pregnancy,
      many in this cohort did not fully understand the counseling that they had
      received. It is important for clinicians to bear in mind that patients may
      express motivation and confidence about using OCs, but still lack knowledge of
      the more complex and critical aspects of OC use. Additional education and support
      are needed in high-risk populations to ensure effective contraceptive knowledge.

PMID- 14642957
TI  - Recurrent, purulent vaginal discharge associated with longstanding presence of a
      foreign body and vaginal stenosis.
AB  - A 13-year-old presented with malodorous, purulent, vaginal discharge following
      each menses for the last three months since menarche. This discharge resolved
      following antibiotic therapy but recurred with each menses. On exam, the patient
      was found to have a blind ending vagina with a small, midline perforation.
      Ultrasound and MRI examinations done prior to surgery did not identify the
      vaginal foreign body. She was taken to the operating room for examination under
      anesthesia and vaginoscopy. During surgery this area was found to be comprised of
      dense adhesions which nearly obliterated the distal vagina. The vaginal adhesions
      were lysed and a plastic foreign body was discovered in the upper vagina. After
      removing the foreign body the superior vagina was undermined, pulled down, and
      sutured to normal inferior vagina. A Mentor mold was placed in the vagina to
      maintain patency.

PMID- 14642958
TI  - Evaluation of irregular menses in perimenarcheal girls: a pilot study.
AB  - Acyclic vaginal bleeding in girls within three years of menarche is most commonly
      attributed to an immature hypothalamic-pituitary-ovarian axis. Assuming this
      diagnosis may preclude the practitioner from performing more definitive studies
      and thereby diagnosing other, treatable causes of menstrual irregularities. A
      retrospective chart review of 178 girls presenting to an inner-city hospital
      based adolescent clinic within three years of menarche was performed. Personal
      and family medical and menarcheal history was assessed, and findings on physical
      and laboratory examination performed were evaluated. Of the 178 girls still
      perimenarcheal at presentation, 47 were the focus of this study. Of these, 39 had
      no significant findings on physical examination, while 3 had signs of functional
      ovarian hyperandrogenism (FOH) including obesity, hirsutism, and moderate acne
      with corresponding LH/FSH ratios>3, although pelvic ultrasound examination
      revealed normal ovaries. Four of the 39 patients with normal physical exams had
      LH/FSH testing done, and 1 of the 4 had an abnormal LH/FSH ratio, indicating
      possible FOH. Two of the 47 patients were pregnant. Other laboratory
      abnormalities included microcytic, hypochromic anemia in patients, and an
      elevated Erythrocyte Sedimentation Rate in a patient later diagnosed with a
      rheumatologic disorder. Those perimenarcheal girls presenting with irregular
      menses and findings including obesity, acne, or pallor, were likely to have
      treatable causes of menstrual irregularities. In one of the four girls with a
      normal physical examination, hormonal testing indicated possible FOH, thus
      suggesting that hormonal evaluation of perimenarcheal girls with menstrual
      irregularities may be justified, as it may reveal previously unsuspected
      pathology.

PMID- 14642959
TI  - To know that we know what we know: perceived knowledge and adolescent sexual risk
      behavior.
AB  - STUDY OBJECTIVE: To examine the relationship between perceived knowledge about
      sex and adolescent sexual behaviors. DESIGN: Secondary analysis of the 2001
      Minnesota Student Survey. Bivariate and multivariate relationships between
      perceived knowledge about sex and sexual behaviors were examined. SETTING:
      Minnesota. PARTICIPANTS: 83,481 9(th) and 12(th) grade public school students.
      MAIN OUTCOME MEASURES: Students' report of sexual experience and sexual
      behaviors. RESULTS: Students with low perceived knowledge were less likely to be
      sexually experienced (OR=0.22, CI=0.17-0.29, females, OR=0.70, CI=0.59-0.82,
      males, P=0.00). Among sexually active students, those with low perceived
      knowledge also had significantly higher odds of engaging in risky sexual
      behaviors. Sexually experienced females with low perceived knowledge were more
      likely to report not talking with their partners about STIs (OR=1.83, CI=1.1
      3.16, P=0.02), a history of pregnancy (OR=2.87, CI=1.59-5.18, P=0.00), and had
      higher numbers of male (P=0.03) and female (P=0.00) sexual partners. Sexually
      experienced males with low perceived knowledge were more likely to report not
      talking with their partners about pregnancy (OR=1.43, CI=1.11-1.84, P=0.01),
      pregnancy involvement (OR=2.22, CI=1.65-2.95, P=0.00), inconsistent use of birth
      control (OR=1.30, CI= 1.01-1.68, P=0.04), inconsistent use of condoms (OR=1.79,
      CI=1.38-2.32, P=0.00), not using a condom at last intercourse (OR=1.58, CI=1.22
      2.04, P=0.00), and had a higher numbers of male (P=0.00) and female (P=0.00)
      sexual partners. CONCLUSIONS: Perceived knowledge may be a salient antecedent of
      adolescent sexual risk behavior. Health care providers and programs should
      incorporate the construct of perceived knowledge into their assessments of and
      interventions targeted at adolescents.

PMID- 14642960
TI  - Opinions in pediatric and adolescent gynecology. Does oral contraceptive therapy
      do more harm than good in adolescents who are receiving chemotherapy?

PMID- 14642961
TI  - Ovarian torsion: to pex or not to pex? Case report and review of the literature.
AB  - STUDY OBJECTIVE: We report the case of a 7-year-old girl who underwent
      laparoscopic ovariopexy for a suspected ovarian torsion after a previous
      oophorectomy. We consider the role of elective ovariopexy of the contralateral
      ovary in the case of adnexal torsion. DESIGN: Case study and review of the
      literature. RESULT: There was evidence to suggest a very recent adnexal torsion
      and an unusually long ovarian pedicle, with a possible familial linkage. The
      patient underwent laparoscopic ovariopexy for the remaining normal ovary, which
      was found to be loosely twisted at operation. After detorsion, ovariopexy was
      performed laparoscopically, by suturing the ovary to the back of uterus. There
      are no other descriptions in the literature of a familial linkage with ovarian
      torsion. CONCLUSION: The case presented reminds doctors of the strong possibility
      of ovarian torsion in young girls presenting with pelvic pain. Laparoscopic
      ovariopexy for the contralateral ovary should be considered in all women with
      evidence of torsion, including children and adolescents, as is standard for
      testicular torsion.

PMID- 14642962
TI  - Management quandary. Irregular menses in adolescents.

PMID- 14642963
TI  - Pelvics, paps, and HPV.

PMID- 14642967
TI  - Animal behavior models of the mechanisms underlying antipsychotic atypicality.
AB  - This review describes the animal behavior models that provide insight into the
      mechanisms underlying the critical differences between the actions of typical vs.
      atypical antipsychotic drugs. Although many of these models are capable of
      differentiating between antipsychotic and other psychotropic drugs, only a few
      seem to be able to differentiate between typical and atypical antipsychotics,
      such as the paw test and the phencyclidine (PCP)-induced disruption of prepulse
      inhibition (PPI) of startle in rats. Moreover, there is an urgent need for animal
      models focusing more on the negative and the cognitive symptoms. Hence, improved
      animal models are crucial for developing better treatments for schizophrenia.

PMID- 14642968
TI  - Half a century of antipsychotics and still a central role for dopamine D2
      receptors.
AB  - A review of the history of antipsychotics reveals that while the therapeutic
      effects of chlorpromazine and reserpine were discovered and actively researched
      almost concurrently, subsequent drug development has been restricted to drugs
      acting on postsynaptic receptors rather than modulation of dopamine release. The
      fundamental property of atypical antipsychotics is their ability to produce an
      antipsychotic effect in the absence of extrapyramidal side effects (EPS) or
      prolactin elevation. Modulation of the dopamine D2 receptor remains both
      necessary and sufficient for antipsychotic drug action, with affinity to the D2
      receptor being the single most important discriminator between a typical and
      atypical drug profile. Most antipsychotics, including atypical antipsychotics,
      show a dose-dependent threshold of D2 receptor occupancy for their therapeutic
      effects, although the precise threshold is different for different drugs. Some
      atypical antipsychotics do not appear to reach the threshold for EPS and
      prolactin elevation, possibly accounting for their atypical nature. To link the
      biological theories of antipsychotics to their psychological effects, a
      hypothesis is proposed wherein psychosis is a state of aberrant salience of
      stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine
      system, dampen the salience of these symptoms. Thus, antipsychotics do not excise
      psychosis: they provide the neurochemical platform for the resolution of
      symptoms. Future generations of antipsychotics may need to move away from a "one
      size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects
      of schizophrenia. At least in theory a preferred approach would be the
      development of specific treatments for the different dimensions of schizophrenia
      (e.g., positive, negative, cognitive, and affective) that can be flexibly used
      and titrated in the service of patients' presenting psychopathology.

PMID- 14642969
TI  - The dopamine D4 receptors and mechanisms of antipsychotic atypicality.
AB  - The dopamine D4 receptor (D4) is a target for most common neuroleptic
      medications. After its initial discovery, it was found to possess the highest
      affinity of all dopamine receptor subtypes for the archetypical, atypical,
      antipsychotic clozapine. Nevertheless, initial clinical trials have not provided
      evidence that this receptor is a primary target for antipsychotic drugs.
      Considering the accumulated in vivo evidence that at least a subgroup of
      psychotic patients have altered dopamine signaling, all dopamine receptor
      subtypes likely contribute to the phenotypic expression of schizophrenia. New
      insights into the function of this receptor and its role in the modulation of
      excitatory signaling support the view that this dopamine receptor may affect
      attention and cognition. In this review, the authors outline some recent
      developments that provide insight into D4 receptor physiology, function and its
      possible relationship to schizophrenia treatment.

PMID- 14642970
TI  - Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality.
AB  - Amisulpride clearly has the clinical profile of an atypical antipsychotic,
      characterised in particular by its lower propensity to induce extrapyramidal side
      effects as well as its greater efficacy in treating negative symptoms compared
      with classical neuroleptics. In addition to the clinical advantages over
      classical neuroleptics, it has also been demonstrated that the clinical profile
      of amisulpride is comparable to that of other modern atypical neuroleptics.
      Animal data also allow the conclusion to be drawn that amisulpride has an
      atypical profile. For example, amisulpride does not provoke catalepsy which is
      characteristic of postsynaptic D2 blockade in the rat. The induction of catalepsy
      in animal models is usually seen as an indicator of the propensity to induce
      extrapyramidal side effects in patients. In relation to the widely accepted
      hypothesis that the inclusion of 5-HT2A antagonism in addition to D2 antagonism
      is of great relevance for the atypicality of an antipsychotic, and given the fact
      that amisulpride lacks 5-HT2A antagonism, the pharmacological explanation of the
      clinically well-proven atypicality of amisulpride is of great interest. Based on
      basic research and in vivo imaging studies, two mechanisms in particular seem to
      explain the atypicality of amisulpride: preferential action on limbic D2/D3
      receptors and preferential blockade of presynaptic D2/D3 receptors. In addition,
      the fast dissociation hypothesis can contribute to the explanation of the
      atypical clinical profile of amisulpride. The relevance of the D3 blockade in the
      context of atypicality is not yet completely clear.

PMID- 14642971
TI  - Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic
      atypicality.
AB  - The neurotransmission mediated by the excitatory amino acids (EAA) glutamate
      (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its
      role in neurodevelopment and neurotoxicity, its complex interactions with
      dopaminergic and other neurotransmitter systems and its pivotal importance in
      recent models of schizophrenia. Accumulating evidence indicates that modulation
      of glutamatergic neurotransmission may play an important role in the mechanisms
      of action of atypical antipsychotic drugs. The principles of the phencyclidine
      (PCP) model of schizophrenia suggest that conventional neuroleptics cannot
      counteract all aspects of schizophrenia symptomatology, while a more favorable
      outcome, including anti-negative and cognitive symptoms effects, would be
      expected with the use of treatment modalities targeting glutamatergic
      neurotransmission. Clozapine and other presently used atypical antipsychotics
      differ from conventional neuroleptics in the way they affect various aspects of
      glutamatergic receptors function. In this context, a specific hypothesis
      suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA)
      subtype of GLU receptors has been postulated. Furthermore, the results of the
      first generation of clinical trials with glycine (GLY) site agonists of the NMDA
      receptor in schizophrenia suggest that this type of compounds (1) have efficacy
      and side effects profiles different than those of conventional neuroleptics and
      (2) differ in their synergic effects when used in addition to conventional
      neuroleptics versus clozapine and possibly additional atypical antipsychotics.
      These findings (1) bring further support to the hypothesis that glutamatergic
      effects may play an important role in the mechanism of action of atypical
      antipsychotics, (2) help explain the unique clinical profile of clozapine, and
      (3) suggest that GLY site agonists of the NMDA receptor may represent a new class
      of atypical antipsychotic medication. Future research in this area is bound to
      bring about a better understanding of the role of glutamatergic neurotransmission
      manipulation in the pharmacotherapy of psychosis and the development of novel
      pharmacological strategies targeting GLU brain systems.

PMID- 14642972
TI  - Muscarinic mechanisms of antipsychotic atypicality.
AB  - The interactions of the atypical antipsychotic drugs (APD) clozapine, olanzapine,
      risperidone, quetiapine and ziprasidone with muscarinic receptors were reviewed.
      Only clozapine and olanzapine have marked affinity for muscarinic receptors in
      radioligand binding studies; however, the affinity of these compounds is
      considerably lower than classical muscarinic antagonists. Although functional
      assays in cell lines transfected with muscarinic receptors suggest that
      olanzapine and clozapine have weak partial agonist activity at muscarinic
      receptors, particularly M4 receptors, studies in vitro and in vivo indicate that
      the compounds function as antagonists. In animal studies and in humans, clozapine
      has pronounced antimuscarinic effects whereas olanzapine has weak antimuscarinic
      effects. However, olanzapine significantly occupies central muscarinic receptors
      in humans. Overall, the role of muscarinic receptors in the antipsychotic effects
      of clozapine and olanzapine is controversial and complex.

PMID- 14642973
TI  - Alpha-adrenoceptor modulation hypothesis of antipsychotic atypicality.
AB  - Although all currently used antipsychotic drugs act as dopamine (DA) D2 receptor
      antagonists, clozapine, the prototype for atypical antipsychotics, shows superior
      efficacy, especially regarding negative and cognitive symptoms, in spite of a
      significantly reduced central D2 receptor occupancy compared with typical
      (conventional) antipsychotic drugs. Clozapine, as well as several other
      atypicals, displays significant affinities also for several other
      neurotransmitter receptors, including other dopaminergic receptors, alpha
      adrenergic receptors and different serotonergic and cholinergic receptors, which
      in several ways may contribute to the clinical effectiveness of the drugs.
      Preclinical and clinical results suggest a dysregulated mesocorticolimbic DA
      system in schizophrenia, with an impaired prefrontal DA projection, which may
      relate to negative and cognitive symptoms, concomitant with an overactive or
      overreactive striatal DA projection, with bearing on psychotic (positive)
      symptomatology. Available data suggest that blockage of alpha1-adrenoceptors by
      antipsychotics may contribute to suppress positive symptoms, especially in acute
      schizophrenia, whereas alpha2-adrenoceptor blockage, a prominent effect of
      clozapine and, to some extent, risperidone but not other antipsychotics, may
      rather be involved in relief of negative and cognitive symptoms. Whereas alpha1
      adrenoceptor blockage may act by suppressing, at the presynaptic level, striatal
      hyperdopaminergia, alpha2-adrenoceptor blockage may act by augmenting and
      improving prefrontal dopaminergic functioning. Thus, the prominent alpha1- and
      alpha2-adrenoceptor blocking effects of clozapine may generally serve to
      stabilize dysregulated central dopaminergic systems in schizophrenia, allowing
      for improved efficacy in spite of a reduced central D2 receptor occupancy
      compared with typical antipsychotic drugs.

PMID- 14642974
TI  - Serotonin receptors: their key role in drugs to treat schizophrenia.
AB  - Serotonin (5-HT)-receptor-based mechanisms have been postulated to play a
      critical role in the action of the new generation of antipsychotic drugs (APDs)
      that are usually referred to as atypical APDs because of their ability to achieve
      an antipsychotic effect with lower rates of extrapyramidal side effects (EPS)
      compared to first-generation APDs such as haloperidol. Specifically, it has been
      proposed by Meltzer et al. [J. Pharmacol. Exp. Ther. 251 (1989) 238] that potent
      5-HT2A receptor antagonism together with weak dopamine (DA) D2 receptor
      antagonism are the principal pharmacologic features that differentiate clozapine
      and other apparent atypical APDs from first-generation typical APD. This
      hypothesis is consistent with the atypical features of quetiapine, olanzapine,
      risperidone, and ziprasidone, which are the most common treatments for
      schizophrenia in the United States and many other countries, as well as a large
      number of compounds in various stages of development. Subsequent research showed
      that 5-HT1A agonism may be an important consequence of 5-HT2A antagonism and that
      substitution of 5-HT1A agonism for 5-HT2A antagonism may also produce an atypical
      APD drug when coupled with weak D2 antagonism. Aripiprazole, the most recently
      introduced atypical APD, and a D2 receptor partial agonist, may also owe some of
      its atypical properties to its net effect of weak D2 antagonism, 5-HT2A
      antagonism and 5-HT1A agonism [Eur. J. Pharmacol. 441 (2002) 137]. By contrast,
      the alternative "fast-off" hypothesis of Kapur and Seeman [Am. J. Psychiatry 158
      (2001) 360] applies only to clozapine and quetiapine and is inconsistent with the
      "slow" off rate of most atypical APDs, including olanzapine, risperidone and
      ziprasidone. 5-HT2A and 5-HT1A receptors located on glutamatergic pyramidal
      neurons in the cortex and hippocampus, 5-HT2A receptors on the cell bodies of DA
      neurons in the ventral tegmentum and substantia nigra and GABAergic interneurons
      in the cortex and hippocampus, and 5-HT1A receptors in the raphe nuclei are
      likely to be important sites of action of the atypical APDs. At the same time,
      evidence has accumulated for the important modulatory role of 5-HT2C and 5-HT6
      receptors for some of the effects of some of the current APDs. Thus, 5-HT has
      joined DA as a critical target for developing effective APDs and led to the
      search for novel drugs with complex pharmacology, ending the exclusive search for
      single-receptor targets, e.g., the D3 or D4 receptor, and drugs that are
      selective for them.

PMID- 14642975
TI  - Psychological manifestations of obesity.

PMID- 14642976
TI  - Exaggerated perception of normal physiological responses to stress and
      hypercapnia in young women with numerous functional somatic symptoms.
AB  - OBJECTIVE: This study tested whether functional somatic symptoms are associated
      with exaggerated increases in self-reported anxiety and somatic complaints in
      response to stress and CO(2)-enriched air breathing, and whether this association
      exists in parallel to or in the absence of exaggerated physiological responses.
      METHODS: Out of 499 young somatically healthy undergraduate women, 18
      participants high in functional somatic symptoms (HSS group) and 18 participants
      low in symptoms (LSS) were selected. They were submitted to mental stress, mild
      physical exercise and relaxation during conditions of normal breathing, breathing
      compressed normal air, and breathing compressed 5% CO(2)-enriched air. In all
      conditions, self-reported anxiety and somatic symptoms and respiratory and
      autonomic responses were assessed. RESULTS: HSS participants reported, as
      compared to LSS, more tenseness, anxiety, and somatic symptoms at baseline and
      increased responses to mental stress and during 5% CO(2) breathing, but not in
      response to exercise. However, no evidence was found for a corresponding
      exaggerated respiratory or autonomic response. CONCLUSIONS: A young, female, and
      nonclinical population with numerous functional somatic symptoms and high levels
      of anxiety is characterized by an exaggerated perception of a normal
      physiological response.

PMID- 14642977
TI  - Challenges to conventional thinking about mind and body.

PMID- 14642978
TI  - Correlations between trait anxiety, personality and fatigue: study based on the
      Temperament and Character Inventory.
AB  - OBJECTIVE: In our study, we explored the associations among anxiety, the
      dimensions of Cloninger's theoretically based and empirically validated
      psychobiological model of personality (Temperament and Character Inventory, TCI)
      and fatigue in order to clarify the personality risk factors for fatigue.
      METHODS: Fifth-year students (n=89) and freshmen (n=162) at Saga Medical School
      and psychiatric outpatients of Saga Medical School Hospital (n=101) were
      investigated with the State-Trait Anxiety Inventory (STAI, Japanese version), the
      TCI (Japanese version), the General Health Questionnaire (GHQ-30) and the self
      rating Fatigue Symptom Checklist (FSC), which describe fatigue along three
      subscales (general, physical and psychological fatigue). Correlation and ANOVA
      analyses were performed in this study. RESULTS: The analysis identified a
      significant relation (P<.0005) between trait anxiety and fatigue. The TCI
      dimension of harm avoidance (HA) is positively correlated with both trait anxiety
      and fatigue (general fatigue, psychological fatigue and physical fatigue). The
      character dimension of self-directedness is negatively correlated with both trait
      anxiety and fatigue. CONCLUSIONS: There is an inherent relationship among trait
      anxiety, the temperament dimension of harm avoidance, character dimension of self
      directedness and fatigue. The TCI dimensions, harm avoidance and self
      directedness, might be considered as predictors for fatigue-related disorders.

PMID- 14642979
TI  - Prevalence of irritable bowel syndrome among university students: the roles of
      worry, neuroticism, anxiety sensitivity and visceral anxiety.
AB  - OBJECTIVE: Relationships between presence of irritable bowel syndrome (IBS) and
      generalized anxiety disorder (GAD), chronic worry, neuroticism, anxiety
      sensitivity and anxiety about visceral sensations were examined among university
      students. METHODS: College student participants were administered self-report
      diagnostic measures of IBS and GAD, the Penn State Worry Questionnaire (PSWQ),
      the Neuroticism subscale of the Eysenck Personality Questionnaire, the Anxiety
      Sensitivity Index (ASI) and five additional items designed to measure visceral
      anxiety. RESULTS: The prevalence of IBS and its associated characteristics among
      students were similar to previous community survey studies, with the exception of
      lower symptom severity in the university sample. IBS was associated with a higher
      frequency of GAD and greater worry, neuroticism, anxiety sensitivity and visceral
      anxiety. Logistic regression analyses further showed that the measure of anxiety
      specific to visceral sensations was the strongest predictor of IBS diagnostic
      status. CONCLUSIONS: While various aspects of anxiety appear related to IBS,
      specific anxiety about visceral sensations appears to be the most significant
      factor. Implications of the associations between anxiety-related variables,
      particularly anxiety about visceral sensations, are discussed.

PMID- 14642980
TI  - Effect of nortriptyline and paroxetine on measures of chaos of heart rate time
      series in patients with panic disorder.
AB  - Tricyclic antidepressants have notable cardiac side effects, and this issue has
      become important due to the recent reports of increased cardiovascular mortality
      in patients with depression and anxiety. Several previous studies indicate that
      serotonin reuptake inhibitors (SRIs) do not appear to have such adverse effects.
      Apart from the effects of these drugs on routine 12-lead ECG, the effects on beat
      to-beat heart rate (HR) and QT interval time series provide more information on
      the side effects related to cardiac autonomic function. In this study, we
      evaluated the effects of two antidepressants, nortriptyline (n=13), a tricyclic,
      and paroxetine (n=16), an SRI inhibitor, on HR variability in patients with panic
      disorder, using a measure of chaos, the largest Lyapunov exponent (LLE) using pre
      and posttreatment HR time series. Our results show that nortriptyline is
      associated with a decrease in LLE of high frequency (HF: 0.15-0.5 Hz) filtered
      series, which is most likely due to its anticholinergic effect, while paroxetine
      had no such effect. Paroxetine significantly decreased sympathovagal ratios as
      measured by a decrease in LLE of LF/HF. These results suggest that paroxetine
      appears to be safer in regards to cardiovascular effects compared to
      nortriptyline in this group of patients.

PMID- 14642981
TI  - Detecting panic disorder in medical and psychosomatic outpatients: comparative
      validation of the Hospital Anxiety and Depression Scale, the Patient Health
      Questionnaire, a screening question, and physicians' diagnosis.
AB  - OBJECTIVES: To compare the validity of detecting panic disorder using the
      Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire
      (PHQ), a screening question, and physicians' diagnosis, and to test whether
      modified evaluation algorithms improve the operating characteristics of these
      questionnaires. Additionally, patient and physician acceptability of the
      screening questionnaires was investigated. METHODS: The total sample of 499
      patients comprised 348 medical outpatients and 151 psychosomatic outpatients. The
      Structured Clinical Interview for DSM-IV (SCID) was the criterion standard for
      the presence of a panic disorder. Sensitivity, specificity, predictive values,
      and overall accuracy were compared for the different measures. The conditional
      test characteristics were calculated based on the observed prevalence of panic
      disorder in the medical and psychosomatic subsample, respectively. RESULTS: Panic
      disorder was diagnosed in 4.3% of the medical outpatients and in 19.2% of the
      psychosomatic outpatients. The HADS, PHQ, and screening question achieved good
      operating characteristics. In contrast, physicians detected only 15% of cases
      with panic disorder. Modified evaluation algorithms of the questionnaires lead to
      an improvement of test characteristics. Of all measures, the PHQ had the best
      operating characteristics. The use of screening questionnaires was accepted by
      96% of the patients and 97% of the physicians. CONCLUSIONS: The questionnaires as
      well as the screening question performed well in detecting panic disorder. Thus,
      the integration of these highly accepted measures into clinical evaluation is
      suggested. Recommendations for the selection of specific evaluation algorithms
      are given.

PMID- 14642982
TI  - Serum lipids responses to a respite from occupational and domestic demands in
      subjects with varying levels of stress.
AB  - OBJECTIVES: To investigate the effect of a temporary respite from domestic and
      job demands on serum lipid concentrations in subjects with high and low levels of
      perceived demands. METHODS: 111 females and 42 males (mean age 57.1+/-9.8)
      staying at a health resort for 3 weeks and receiving spa treatments participated
      in the study. Serum cholesterol (CHOL), high-density lipoprotein cholesterol (HDL
      c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and LDL/HDL
      were measured at the beginning and end of the stay. In addition, levels of
      perceived demands were assessed. Data were analysed with MANCOVA for repeated
      measures with known confounding variables as covariates. RESULTS: Subjects with a
      higher level of perceived demands had higher levels of CHOL, LDL/HDL and TG and
      lower levels of HDL-c. In response to the respite, subjects experiencing more
      demands showed a greater decrease of LDL-c (P<.01) and LDL/HDL (P<.001). Sex
      moderated these stress-related respite effects for HDL-c (P<.01) and LDL/HDL
      (P<.005), high demand males showing a smaller decrease in HDL and a greater
      decrease in LDL/HDL than females in response to the respite. CONCLUSIONS: The
      results indicate that a respite from chronic demands may reduce LDL-c and LDL/HDL
      in chronically stressed individuals.

PMID- 14642983
TI  - Possible variances of blood urea nitrogen, serum potassium and phosphorus levels
      and interdialytic weight gain accounted for compliance of hemodialysis patients.
AB  - OBJECTIVES: The aim of this study was to assess the possible variances of blood
      urea nitrogen (BUN), serum potassium (SK) and serum phosphorus (SPO(4)) levels
      and interdialytic weight gain (IWG) accounted for compliance of uremic patients
      on hemodialysis (HD). METHODS: BUN, SK and SPO(4) levels and IWG of uremic
      patients (n=310) regularly undergoing three HD sessions per week for more than 1
      year in Japan were assessed. Patients suffering from problems influencing dietary
      intake and those with malnutrition were excluded. The variances accounted for
      self-efficacy for health-related behavior and avoidance-oriented coping (AOC)
      with stress were assessed by hierarchical multiple regression analyses. RESULTS:
      BUN and SPO(4) levels were not significantly (P<.05) associated with self
      efficacy or AOC. SK levels and IWG were significantly (P<.05) associated with
      self-efficacy and/or AOC. The variances of SK levels and IWG accounted for self
      efficacy and/or AOC, independent of age, sex, duration of HD and facilities, were
      1.6% and 5.0%, respectively. CONCLUSIONS: Although the variances of SK levels and
      IWG accounted for self-efficacy and/or AOC were rather small, the significance of
      their relationships may suggest that intervention for self-efficacy or AOC could
      improve compliance and reduce SK levels and IWG of uremic patients on HD.

PMID- 14642984
TI  - Adaptive defense use and resting blood pressure in a population-based sample.
AB  - OBJECTIVES: There is an accumulating body of research related to the
      psychosomatic study of blood pressure. One variable that has received attention
      is defense use. We examined the relation between defense use and blood pressure
      in men and women of different ages. METHODS: A random sample of 667 participants
      was selected from a population-based study. Resting blood pressure was obtained,
      and each participant was rated for defense use by a trained observer using
      Defense-Q. An Adaptive Defense Profile (ADP) score was calculated for each
      participant, and this score was related to blood pressure. RESULTS: Regression
      analyses revealed a significant main effect for the ADP score for both diastolic
      and systolic blood pressure. Those persons with higher ADP scores had lower
      diastolic and systolic blood pressure. As well, a significant Age x Sex x ADP
      score interaction was found for diastolic blood pressure. Older women with a less
      ADP score had higher diastolic blood pressure. CONCLUSIONS: These findings
      suggest the continued investigation of defense use and blood pressure.

PMID- 14642985
TI  - Alternative medicine and allergies: life satisfaction, health locus of control
      and quality of life.
AB  - OBJECTIVES: Little is known on psychosocial characteristics of subjects with
      allergies who use or do not use alternative medicine (AM). We aimed to assess
      health-related quality of life (QoL), life satisfaction and health locus of
      control of adults with allergies and to compare users and nonusers of AM in a
      population-based setting. METHODS: In a population-based nested case control
      study, computer-assisted telephone interviews were performed in subjects (n=351,
      age median 46 years, response 76.1%) who had reported allergies (hay fever,
      asthma, atopic eczema and food hypersensitivity) in a previous survey. Questions
      on health-related QoL and evaluated instruments measuring life satisfaction
      ("Questions on Life Satisfaction" (FLZ(M))) and health locus of control
      ("Fragebogen zur Erhebung von Kontrolluberzeugungen zu Krankheit und Gesundheit"
      (KKG)) were applied. RESULTS: A total of 93 subjects (26.6%), who were younger
      and better educated than the remaining participants (n=257), reported experiences
      with AM. General and health-related life satisfaction was not statistically
      different between users (71.5 and 71.6) and nonusers (68.5 and 67.0) of AM.
      Nonusers scored significantly higher for fatalistic externality (21.6) than users
      (19.0) of AM (P=.005, adjusted age, gender and school education). The impact on
      overall health-related QoL was significantly higher for users (11.7) than
      nonusers (10.3) of AM. This difference was also significant for the domains
      "physical," "psychological," "friends and family" and "leisure activities"
      (adjusted P<.001). CONCLUSIONS: Users and nonusers of AM with allergies can be
      distinguished by psychosocial characteristics such as health locus of control and
      QoL.

PMID- 14642986
TI  - Use of complementary therapy among internal medical inpatients. Prevalence, costs
      and association with mental disorders and physical diseases.
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of
      complementary therapy/medicine (CT) use among internal medical inpatients.
      Furthermore, to examine the association between the use of CT and (a) mental
      disorders, (b) physical diseases, and (c) use of health care. METHODS: A total of
      294 consecutive medical inpatients were interviewed about their use of CT. A
      stratified subsample of 157 people was assessed for current mental disorders,
      using an extensive, standardized, semistructured interview (Schedules for
      Clinical Assessment in Neuropsychiatry version 2.1 [SCAN]). Health care use was
      assessed by use of national patient registers. RESULTS: There were 22.5% CT
      utilizers. More females than males used CT (P=.033). CT utilization was not
      associated with age, mental disorders, life-threatening or chronic physical
      diseases or with use of health care services. CONCLUSIONS: The use of CT is
      common among medical inpatients. More research is needed to understand why a
      significant proportion of patients seeks CT.

PMID- 14642987
TI  - Alexithymia in parents of daughters with eating disorders: its relationships with
      psychopathological and personality variables.
AB  - OBJECTIVES: The purpose of this research was to investigate alexithymia among
      parents of a daughter with eating disorders (EDs) and to relate alexithymia to
      personality and psychopathology characteristics. METHODS: Parents of 73 women
      with ED (20 with anorexia nervosa, restrictive subtype (ANR), 23 with anorexia
      nervosa, bulimic subtype (ANB) and 30 with bulimia nervosa (BN)) and parents of
      72 normal women were evaluated with the Toronto Alexithymia Scale (TAS-20), the
      Eysenck Personality Questionnaire, the Beck Depression Inventory and the Self
      Rating Anxiety Scale. RESULTS: The parents of daughters with ED show higher
      scores in the TAS-20 and its factors than the controls. TAS-20 scores of parents
      are associated with neuroticism, anxiety and depression. CONCLUSIONS: Alexithymia
      in parents of daughters with an ED could be a trait of personality, but it could
      also be a state due to distress. Alexithymia should be taken into account in
      order to help these parents express emotions.

PMID- 14642988
TI  - Is there a reliable factorial structure in the 20-item Toronto Alexithymia Scale?
      A comparison of factor models in clinical and normal adult samples.
AB  - OBJECTIVES: The 20-item Toronto Alexithymia Scale (TAS-20) is the most widely
      used instrument for measuring alexithymia. However, different studies did not
      always yield identical factor structures of this scale. The present study aims at
      clarifying some discrepant results. METHODS: Maximum likelihood confirmatory
      factor analyses of a German version of the TAS-20 were conducted on data from a
      clinical sample (N=204) and a sample of normal adults (N=224). Five different
      models with one to four factors were compared. RESULTS: A four-factor model with
      factors (F1) "Difficulty identifying feelings" (F2), "Difficulty describing
      feelings" (F3), "Low importance of emotion" and (F4) "Pragmatic thinking" and a
      three-factor model with the combined factor "Difficulties in identifying and
      describing feelings" described the data best. Factors related to "externally
      oriented thinking" provided no acceptable level of reliability. CONCLUSIONS:
      Results from the present and other studies indicate that the factorial structure
      of the TAS-20 may vary across samples. Whether factor structures different from
      the common three-factor structure are an exception in some mainly clinical
      populations or a common phenomenon outside student populations has still to be
      determined. For a further exploration of the factor structure of the TAS-20 in
      different populations, it would be important not only to test the fit of the
      common three-factor model, but also to consider other competing solutions like
      the models of the present study.

PMID- 14642989
TI  - Life events, perceived stress and antibody response to influenza vaccination in
      young, healthy adults.
AB  - OBJECTIVES: Chronic stress has been associated with impaired response to
      influenza vaccination in the elderly. This study investigated whether mild,
      intermittent stress experienced by young, healthy adults has a similar effect.
      METHODS: Antibody and psychological status were determined prevaccination and 5
      weeks and 5 months later; a fourfold increase in antibody to at least one viral
      strain was considered protective. RESULTS: At 5 months, unprotected participants
      reported significantly more life events and tended to report more perceived
      stress than those who were protected. CONCLUSIONS: Psychological stress is
      detrimental to long-term maintenance of antibody levels following vaccination in
      young, healthy adults.

PMID- 14642990
TI  - Recurrent brief depression in celiac disease.

PMID- 14642991
TI  - The impact of temporal lobe surgery on cure and mortality of drug-resistant
      epilepsy: summary of a workshop.
AB  - The Third International Spring Epilepsy Research Conference took place in
      Georgetown, Cayman Islands from April 26 to May 3, 2003. One workshop discussed
      the impact of epilepsy surgery on seizure outcome and mortality of antiepileptic
      drug (AED)-resistant temporal lobe epilepsy. This article summarizes the
      information presented at this workshop. Although two-thirds of adult patients
      undergoing epilepsy surgery become seizure-free with continued AED treatment,
      current clinical experience shows that seizure recurrence occurs in one-third of
      patients when AEDs are withdrawn under medical supervision. Additional seizure
      recurrence occurring after AED taper, poor drug compliance and even while
      patients continue on AEDs after surgery leave only approximately one-third of
      patients cured after temporal lobe resection. Mostly because so many patients
      prefer to stay on AEDs although they are free of disabling seizures after
      surgery, a randomised controlled trial of AED discontinuation is needed to
      determine if in fact only one-third of patients are cured after surgery. Based on
      the functional anatomy of temporal lobe surgery two hypotheses are presented why
      only a minority of patients are cured after surgery. The type and the prognostic
      significance of seizures after surgery is discussed. Recent studies have
      suggested that successful temporal lobe surgery may be able to normalize the
      increased standard mortality ratio (SMR) of drug-resistant temporal lobe
      epilepsy. However, pre-existing differences in SMR between those cured and those
      not cured by temporal lobe surgery and other unresolved methodological issues
      make it difficult at present to fully evaluate the impact of surgery on
      mortality. Future studies are thus warranted to specifically address the impact
      of temporal lobe surgery on cure and mortality.

PMID- 14642992
TI  - How effective is surgery to cure seizures in drug-resistant temporal lobe
      epilepsy?
AB  - It is well recognized that two-thirds of patients with drug-resistant temporal
      lobe epilepsy will be free of disabling seizures with continued medical treatment
      after temporal resection. Seizure recurrence has been noted during a five-year
      follow-up in approximately one-third of these seizure-free patients mostly but
      not exclusively following planned complete discontinuation of antiepileptic drugs
      (AEDs). This leaves one-third of patients without disabling seizures and without
      AEDs several years after surgery. Despite improvements in seizure frequency or
      severity, seizures persist in another third of patients undergoing surgery.
      Although cure (five years without any seizures and off AEDs) is the ultimate aim
      of epilepsy surgery, the percentage of patients cured by surgery cannot be well
      defined at the moment. We need a long-term randomized controlled trial on AED
      discontinuation in seizure-free patients followed by long-term open extension to
      determine if only one in three adult patients with drug-resistant temporal lobe
      epilepsy is cured by surgical intervention.

PMID- 14642993
TI  - Why does surgery fail to cure limbic epilepsy? Seizure functional anatomy may
      hold the answer.
AB  - Surgery for the mesial temporal lobe epilepsy syndrome is highly effective in
      controlling seizures in as many as 80% of the patients who undergo this
      procedure. However, the majority of the patients with successful operations still
      require medications to control their seizures. Only a small minority are able to
      stop medications and remain seizure free, patients who would be considered cured.
      Why are so few patients cured by this procedure? The answer may lie in the
      relation of the critical seizure circuits to the tissue that is actually
      resected. In this paper we will discuss two hypotheses for the functional anatomy
      of limbic epilepsy in light of what is known about the pathology and physiology
      of limbic epilepsy. Combining the clinical and scientific observations with these
      constructs for seizure initiation may lead us to a better understanding of this
      particular epilepsy syndrome as well as to more effective surgical approaches.

PMID- 14642994
TI  - Seizures after epilepsy surgery.
AB  - This article reviews types and prognostic significance of seizures that occur
      after epilepsy surgery, so-called postsurgical seizures.

PMID- 14642995
TI  - Does epilepsy surgery lower the mortality of drug-resistant epilepsy?
AB  - Drug-resistant epilepsy has proved to be associated with an increased
      standardized mortality ratio (SMR), primarily due to seizure-related fatalities
      including sudden unexpected death (SUDEP). Recent studies have suggested that the
      surgical cure of temporal lobe epilepsy (TLE) was likely to normalize the SMR of
      patients suffering from refractory TLE. However, these studies raise a number of
      methodological issues, which have not always been fully addressed. Some
      conclusions have relied on previously reported data, indicating a SMR of
      approximately 5, and a SUDEP incidence of 9/1000 patient-years in drug-resistant
      epilepsy. In fact, as shown in this review, SMR varied considerably, from 2 to
      16, in the various series of patients with refractory epilepsy, whereas the
      average SUDEP incidence in the same populations was calculated at 3.7/1000
      patient-years. Other conclusions were based on the comparison of either
      surgically and medically treated patients, or cured and non-cured operated
      patients. In both situations, the two groups included a different proportion of
      excellent and poor surgical candidates. The biological differences that
      distinguish these two populations might explain part of the differences observed
      in their mortality rate, regardless of the effect of surgery. In particular,
      temporal-plus epilepsies involving the insula, the frontal orbital, or the
      frontal operculum region, might favour ictal arrhythmias, central apnoea and
      secondary generalization, which in turn would increase the risk of SUDEP. Future
      studies are thus warranted to specifically address these issues.

PMID- 14642996
TI  - Levetiracetam does not alter body weight: analysis of randomized, controlled
      clinical trials.
AB  - INTRODUCTION: Increases in body weight gain are important, and clinically
      significant adverse effects of several antiepileptic drugs (AED) including
      valproate and gabapentin. Weight gain may contribute to medication non
      compliance, discontinuation, and importantly, may have secondary medical
      implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment
      of partial seizures. The objective of the present evaluation was to examine the
      effects of LEV treatment on body weight in adult patients. METHODS: We analyzed
      data derived from four prospective, placebo-controlled randomized, clinical
      trials conducted in both in the US and Europe. Patients included in the present
      analysis were both men and women, greater than 16 years old, and who had LEV
      exposure for at least 1 month. Body weight was measured at baseline and at the
      final LEV study visit. Data are analyzed for all patients, by gender, body mass
      index (BMI), duration of LEV exposure and by concomitant AED treatment. Wilcoxan
      Signed Rank, or Rank Sum test used where appropriate, with significance assigned
      at P<0.05. Data are presented as mean values+/-1 S.D. RESULTS: Nine-hundred and
      seventy patients (age=37.5 years, 54% men/46% women) were evaluated. There were
      no significant differences in baseline demographics between LEV (n=631) or
      placebo (n=339) treated patient groups. Mean LEV dose and duration of treatment
      were 2053 mg/day (maximum dose of 4000 mg/day) and 125 days (maximum=181 days),
      respectively. Concomitant AED therapy included CBZ, PHT, VPA, PB, GBP, LTG, and
      VGB. For LEV-treated patients, no significant changes in body weight were noted.
      Mean body weight at baseline versus final study visit for LEV was 74.3+/-16.6 kg
      and 74.3+/-16.6 kg, respectively. For placebo-treated patients, baseline versus
      end of treatment weight was 72.4+/-15.4 kg and 72.7+/-15.9 kg, respectively,
      representing a slight, yet clinically trivial increase. Clinically significant
      weight change as defined as >7% change from baseline weight, occurred in 9% of
      LEV-treated patients (4.5% had increase in weight/4.5% decrease) versus 9.4%
      (5.9% had increase/3.5% decrease) in placebo-treated patients. Weight changes
      were not significantly different between groups. Neither baseline BMI, gender, or
      background AEDs, appeared to predispose to significant weight change for LEV
      treated patients. CONCLUSIONS: We conclude that treatment with LEV at clinically
      relevant dosages is not associated with significant weight change. LEV would,
      therefore, appear to be a weight neutral AED.

PMID- 14642997
TI  - Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy.
AB  - Myoclonic astatic epilepsy (MAE) is a genetically determined condition of
      childhood onset characterized by multiple generalized types of seizures including
      myoclonic astatic seizures, generalized spike waves and cognitive deterioration.
      This condition has been reported in a few patients in generalized epilepsy with
      febrile seizures plus (GEFS+) families and MAE has been considered, like severe
      myoclonic epilepsy of infancy (SMEI), to be a severe phenotype within the GEFS+
      spectrum. Four genes have been identified in GEFS+ families, but only three
      (SCN1A, SCNlB, GABRG2) were found in MAE patients within GEFS+ families. We
      analysed these three genes in a series of 22 sporadic patients with MAE and found
      no causal mutations. These findings suggest that MAE, unlike SMEI, is not
      genetically related to GEFS+. Although MAE and SMEI share the same types of
      seizures, only SMEI patients are sensitive to fever. This is probably its main
      link to GEFS+. A different family of genes is likely to account for MAE.

PMID- 14642998
TI  - Tolerability of levetiracetam in elderly patients with CNS disorders.
AB  - The purpose of this analysis was to compare treatment-emergent adverse events
      (TEAE) related to use of levetiracetam (LEV) reported by young and elderly
      patients with anxiety and cognitive disorders, and young epilepsy patients. The
      LEV database includes reports of TEAE from trials of patients with diagnoses of a
      cognitive disorder (N=719), an anxiety disorder (N=1510), or localization-related
      epilepsy (N=1023) who participated in clinical trials lasting up to 16 weeks.
      Patients were grouped as young (<65 years) or elderly (> or = 65 years). The most
      common TEAE occurring most frequently in the LEV-treated groups were abdominal
      pain, asthenia, headache, anorexia, weight loss, dizziness, insomnia, somnolence,
      and tremor. The only significant differences in TEAE were seen between young and
      elderly groups with anxiety disorders (>3% higher for LEV than for placebo
      treated patients) in headache (5.2% elderly, -0.9% young, P=0.041), and tremor
      (5.2 and -0.5%, respectively, P=0.022) and between young anxiety patients and
      young epilepsy patients for somnolence (-0.7 and 5.4%, respectively, P=0.036).
      For the other TEAEs there was no evidence for consistent differences between
      young and elderly patients and between patients with different CNS disorders.
      Overall, LEV was well tolerated by all patient groups. The favorable adverse
      event profile suggests that LEV might be suitable for use by elderly patients.

PMID- 14642999
TI  - Assessment of copper status in epileptic patients treated with anticonvulsant
      drugs by measuring the specific oxidase activity of ceruloplasmin.
AB  - Significant increases in serum levels and decreases in hair copper levels have
      been previously described in epileptic patients treated with anticonvulsant
      drugs. A condition not directly related to copper nutriture, such as chronic
      treatment with these drugs, could increase the serum concentrations of copper and
      ceruloplasmin and would mask a possible copper deficiency produced by drug
      increased biliary copper excretion. Serum immunoreactive ceruloplasmin
      concentration and its oxidase activity were determined in 90 adult epileptic
      patients treated with phenobarbital (n=60), phenytoin (n=70), carbamazepine
      (n=33) and valproic acid (n=8). The levels of ceruloplasmin and oxidase activity
      were significantly higher (P<0.001) than in an age and gender-matched control
      group (n=49). The significant correlations (P<0.01) between ceruloplasmin and the
      urinary excretion of D-glucaric acid, serum gamma-glutamyltransferase (GGT) and
      drug score in the patients group, would suggest that phenobarbital-type enzyme
      inducing agents may increase the hepatic synthesis of ceruloplasmin. In 11
      patients with a beta-globulin migrating GGT isoform (GGT3), a sensitive marker of
      cholestasis, the levels of ceruloplasmin, oxidase activity and total GGT activity
      were significantly higher (P<0.05) than in the group of 79 patients without the
      GGT3 isoform; consequently, in some cases a drug-induced cholestasis may also
      contribute to the increase of serum copper and ceruloplasmin. The values obtained
      for the specific oxidase activity of ceruloplasmin (activity per unit mass of
      enzyme protein) suggest that in the most of the cases, chronic administration of
      phenobarbital, phenytoin, carbamazepine or valproic acid, does not produce
      marginal or moderate copper deficiency.

PMID- 14643000
TI  - Characterization of a 6p21 translocation breakpoint in a family with idiopathic
      generalized epilepsy.
AB  - The idiopathic generalized epilepsies (IGE), for which a genetic cause is widely
      accepted, account for 20-30% of all epilepsies. Mapping these epilepsies is
      difficult, but progress in the positional cloning of idiopathic epilepsy genes
      responsible for monogenic forms provide emerging evidence that many idiopathic
      epilepsies are caused by mutations in genes coding for ion channels. Here, we
      show the characterization of a balanced translocation present in three members of
      a nuclear family, two of them affected with IGE. The translocation involved
      chromosome 6p21 [t(4;6) (q35;p21)], a region in which a susceptibility locus for
      IGE (EJM1) has been reported. Fluorescence in situ hybridization analysis with
      YACs and PACs resulted in the identification of a PAC clone that included the
      6p21 translocation breakpoint. The genomic sequence of this PAC clone contains
      two 2-pore potassium channel genes, TALK-1 and TALK-2. We characterized the
      genomic organization of both genes, including three different isoforms of TALK-1,
      and investigated them in IGE patients, finding some polymorphisms in the coding
      sequence of TALK-1A.

PMID- 14643001
TI  - The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the
      extracellular levels of amino acids and energy metabolites in a model of iron
      induced posttraumatic epilepsy.
AB  - This study investigates astrocytic glutamate uptake in the iron-induced animal
      model of posttraumatic epilepsy. Since formation of free radicals may be involved
      in epileptogenesis after brain trauma and hemorrhage the effects of the nitrone
      radical scavenger alpha-phenyl-tert-N-butyl nitrone (PBN) were also studied.
      Animals received an intracortical iron injection, or were sham-operated. They
      were given PBN intraperitoneally or saline as control. Twenty-four hours after
      lesion, brain tissue was collected and the level of glial glutamate transporter
      (GLT-1) was analyzed using immunoblotting. The extracellular concentrations of
      amino acids and energy metabolites were measured using microdialysis. The results
      showed significantly decreased levels of GLT-1 (70 kDa), higher basal levels of
      glutamate, and lower levels of glutamine as well as low arginine/citrulline
      ratios at the lesion compared to controls. PBN significantly attenuated the
      decrease of 70 kDa GLT-1 in the lesioned animals and attenuated the alterations
      in amino acid levels but not to a significant level. PBN also increased the
      arginine/citrulline ratios indicating reduced nitric oxide synthase activity. Our
      results suggest that astrocytic uptake of glutamate is oxidatively impaired in
      iron-induced epileptogenesis and that the administration of a radical scavenger
      can attenuate this process.

PMID- 14643002
TI  - Gene expression profile analyses of cortical dysplasia by cDNA arrays.
AB  - Cortical dysplasia (CD) is a well-recognized cause of intractable epilepsy,
      especially in children and is characterized histologically by derangements in
      cortical development and organization. The objective of this study was to expand
      the current knowledge of altered gene expression in CD as a first step towards in
      the identification of additional genes operative in the evolution of CD. Surgical
      specimens were obtained from eight patients (4 males and 4 females; age range 2
      38 years; mean 15 years) with a pathologic diagnosis of CD. Nondysplastic
      temporal neocortex was obtained from a 2-year-old boy with intractable epilepsy
      and medial temporal lobe ganglioglioma. After total RNA isolation from frozen
      brain tissues, we carried out gene expression profiling using a cDNA expression
      array. Differences in gene expressions between CD and the nondysplastic neocortex
      were confirmed by semi-quantitative conventional reverse transcription-PCR. Three
      genes (recombination activating gene 1 (RAG1), heat shock 60 kDa protein 1 (HSP
      60), and transforming growth factor beta1 (TGF beta1)) were found to be up
      regulated more than two-fold in CD, whereas four genes (phosphoinositide-3-kinase
      regulatory subunit polypeptide 1 [p85 alpha] (PI3K), frizzled homolog 2
      [Drosophila], Bcl-2/adenovirus E1B 19 kDa interacting protein (NIP3), and glia
      maturation factor beta (GMF beta)) were down-regulated to less than 50% of their
      normal levels. Interestingly, the majority of genes showing altered expression
      were associated with apoptosis. Our study demonstrates diverse changes in gene
      expression in CD. However, it remains to be shown which of these are causally
      related to the evolution of CD.

PMID- 14643003
TI  - Electrobehavioral characteristics of epileptic rats following photothrombotic
      brain infarction.
AB  - The goal of this study was to characterize the electroencephalographic (EEG) and
      behavioral properties of young adult rats during extended video-EEG monitoring
      following photothrombotic brain infarction. Two-month-old male Sprague-Dawley
      rats underwent photothrombotic brain infarction of the left sensorimotor cortex
      with the photosensitive dye rose bengal (n=10) or were used as controls (n=9).
      Qualitative and quantitative EEG analysis was performed on digital video-EEG
      records obtained during 6 months of recording. The main finding of this study was
      that 5/10 (50%) lesioned animals developed focal epileptic seizures ipsilateral
      to the cortical infarct characterized by rhythmic spike-wave discharges with or
      without behavioral change. Epileptic animals demonstrated increased delta, theta,
      and low beta-range power ipsilateral to the infarct that reliably distinguished
      them from lesioned nonepileptic and control animals. Lesioned animals (epileptic
      and nonepileptic) also demonstrated a distinct pattern of focal rhythmic theta
      activity before or after generalized high beta-range discharges. Electrical and
      behavioral characteristics common to both lesioned and control animals included:
      (1) focal rhythmic theta activity in either hemisphere; (2) focal low beta-range
      discharges in either hemisphere; (3) generalized high beta-range discharges; (4)
      absence seizures; (5) generalized pseudoperiodic spike discharges associated with
      mild multifocal body jerks; (6) tonic-clonic seizures (one nai;ve control; one
      lesioned animal). Cresyl violet staining of lesioned animals' brains showed
      consistent infarcts of the sensorimotor cortex extending to the subcortical white
      matter. These results provide an expanded electrobehavioral description of young
      adult rats following photothrombotic brain infarction and augment further
      investigation into the molecular, cellular, and network alterations that
      contribute to the establishment of post-stroke epilepsy.

PMID- 14643004
TI  - No evidence for a seriously increased malignancy risk in LGI1-caused epilepsy.
AB  - The Leucine-rich Glioma Inactivated-1 (LGI1) gene is supposed to be a tumor
      suppressor gene involved in glial tumors. Mutations in this gene were recently
      found to cause autosomal dominant lateral temporal lobe epilepsy (ADLTE). We have
      now analysed the comorbidity in a large Norwegian ADLTE family. No evidence was
      found that LGI1 is a high-penetrance tumor suppressor gene associated with a
      serious risk for malignancies in ADLTE families.

PMID- 14643006
TI  - Direct cell-cell contact required for neurotrophic effect of chromaffin cells on
      neural progenitor cells.
AB  - Previous studies showed that neural progenitor cultures could be maintained
      without exogenously added FGF-2 when co-cultured with chromaffin cells. In
      addition, progenitor cells displayed dramatically increased neuronal
      differentiation in the presence of chromaffin cells. These findings suggested an
      approach to improved neural progenitor transplant outcomes using co
      transplantation or administration of chromaffin cell-derived factors. The aim of
      this study was to determine whether the observed survival and differentiation
      effects were due to diffusible factors or required direct cell-cell contact (DC).
      Rat neural progenitors were cultured under six different conditions: (1) Standard
      N2 media with FGF-2; (2) N2 without FGF-2; (3) N2 with FGF+conditioned media (CM)
      from chromaffin cultures; (4) N2 without FGF-2+CM; (5) Transwells (TW),
      progenitor+chromaffin cells grown together but separated by a membrane allowing
      movement of diffusible agents but preventing direct contact; (6) direct contact
      co-cultures of progenitors and chromaffin cells. Cultures were evaluated for
      survival, proliferation, and differentiation. Cultures with FGF-2 proliferated
      and formed floating neurospheres while those grown in N2 without FGF-2 failed to
      thrive. Those grown either with CM or in transwells showed significantly improved
      survival. Survival was comparable to the exogenous FGF groups when progenitors
      were allowed direct contact with chromaffin cells. Proliferation was low in all
      cultures except those receiving exogenous FGF-2. Direct contact co-cultures
      exhibited a marked increase in beta-tubulin III+ processes compared to all other
      groups, indicating differentiation towards a neuronal phenotype. The results of
      this study suggest that diffusible agents produced by chromaffin cells can
      sustain viable progenitor cells in vitro even in the absence of added FGF-2 but
      that the effects on progenitor cell neuronal differentiation require direct cell
      cell contact.

PMID- 14643007
TI  - Dexamethasone exposure during the neonatal period alters ORL1 mRNA expression in
      the hypothalamic paraventricular nucleus and hippocampus of the adult rat.
AB  - Dexamethasone is commonly used to limit the severity of chronic lung disease in
      premature infants with severe respiratory distress syndrome. Recent literature
      has demonstrated an association between dexamethasone exposure in critically ill
      premature neonates and later development of cerebral palsy. However, the majority
      of children exposed to dexamethasone in the neonatal period do not develop
      cerebral palsy or global developmental delay, and other more subtle effects of
      early life glucocorticoid exposure may go unnoticed. Presently, little is known
      regarding possible effects of early dexamethasone exposure on development of
      neuropeptide systems that are sensitive to glucocorticoid modulation. One such
      system is the pain-related opioid system that interacts with the stress-related
      limbic-hypothalamic pituitary adrenal (LHPA) axis. In the present study, a
      neonatal rat model was used to expose newborn rats to dexamethasone. Using a
      within-litter design, on postnatal days P3 through P6, pups were either handled,
      or they received a daily intramuscular injection of saline or dexamethasone.
      Adult animals were sacrificed on day of life P120, their brains were removed and
      quick-frozen. Using in situ hybridization histochemistry, mRNA expression of the
      opioid receptor-like (ORL1) receptor was measured in the paraventricular nucleus
      of the hypothalamus (PVN) and the hippocampal formation. In dexamethasone-treated
      adult male rats, ORL1 mRNA expression was increased in the PVN and dentate gyrus,
      but decreased in area CA1, when compared to handled and vehicle controls. These
      results suggest that prolonged glucocorticoid receptor (GR) occupation in the
      neonatal period leads to permanent alterations in ORL1 expression in the LHPA
      stress axis of the adult rat.

PMID- 14643008
TI  - Cell death in the nasal septum of normal and naris-occluded rats.
AB  - Blocking airflow through an external naris of a newborn rat results in a thinning
      of the olfactory mucosa by postnatal day (P) 20, at least partially due to a
      reduction in mitotic rates. We employed the TUNEL method to examine patterns of
      cell death. By P20-30, significant differences in the numbers of labeled profiles
      were found in the middle 50% of the tissue, a region primarily containing
      olfactory sensory cells.

PMID- 14643009
TI  - Manipulating transmitter release at the neuromuscular junction of neonatal rats
      alters the expression of ChAT and GAP-43 in motoneurons.
AB  - During early postnatal development, motoneurons innervating rat hindlimb muscles
      die following injury to the sciatic nerve. However, prematurely enhancing
      transmitter release from nerve terminals of neonatal rats renders motoneurons
      less vulnerable to nerve injury, whereas reducing transmitter release increases
      their susceptibility to injury. Thus, alterations in transmitter release may have
      an influence on motoneuron phenotype. Here we investigated the relationship
      between the vulnerability of motoneurons to injury, and the expression of
      proteins associated with axonal growth and neuromuscular transmission. We
      examined the effect of agents that affect transmitter release from nerve
      terminals and that have been shown to influence the expression of transmitter and
      growth related proteins in developing motoneurons in response to nerve injury. In
      newborn rats, implants containing either 4-aminopyridine (4-AP), to increase
      transmitter release, or magnesium sulphate (MgSO4), to decrease release, were
      applied to the soleus muscle in one hindlimb. The effect of these treatments on
      the activity of choline acetyltransferase (ChAT) in nerve terminals in the soleus
      muscle was measured using a radiochemical assay. Levels of GAP-43 in sciatic
      nerve were also assessed, by Western blot analysis. The results showed that
      during normal development, there was a gradual increase in ChAT activity during
      the second week of postnatal development, whereas GAP-43 levels declined sharply
      between postnatal days 12-14. However, following 4-AP treatment, there was a
      dramatic increase in ChAT activity in nerve terminals contacting the treated
      soleus muscles and the levels of GAP-43 in the sciatic nerve declined at an
      earlier age than normal. Conversely, following treatment with MgSO4 the normal
      increase in ChAT activity that occurs during the second postnatal week was
      delayed, and GAP-43 levels in the sciatic nerve were maintained for significantly
      longer than normal. Thus, manipulating transmitter release from nerve terminals
      in neonatal rats alters the normal pattern of expression of transmitter and
      growth related proteins in developing motoneurons. This alteration in protein
      expression may influence both the maturation of motoneurons and their ability to
      withstand nerve injury.

PMID- 14643010
TI  - Changes in the postnatal development on nitric oxide system induced by serotonin
      depletion.
AB  - Serotonin (5-HT) is expressed early during central nervous system (CNS)
      development and plays an important role during this period. Nitric oxide (NO) is
      also involved in neuronal development. Morphological and functional relationships
      between NO and 5-HT, demonstrated as alterations of the nitrergic system, were
      observed after a 5-HT depletion. It has been hypothesized that NO may be related
      to the neuronal damage induced by some 5-HT neurotoxins. A parachloroamphetamine
      (PCA) treatment is able to damage ascending 5-HT fibers proceeding from the
      dorsal raphe nucleus (DRN) and depletes 5-HT storage in neuronal somata. In order
      to study the effects of a 5-HT depletion on the nitrergic system during postnatal
      development, Wistar rat pups were injected subcutaneously twice, on postnatal day
      (PND) 3 and PND4 with PCA. Neuronal nitric oxide synthase (nNOS) immunoreactivity
      and NADPH diaphorase reactivity were performed on brain sections from PND5, 7,
      12, 19, 29 and 62 animals. After the treatment, we found an increased NADPH-d
      staining and nNOS immunoreactivity in striatum, frontal cortex and hippocampus
      along the different studied time periods. Interestingly, the expression of both
      NO markers was higher when 5-HT depletion was more evident, suggesting a very
      close relationship between 5-HT and NO systems during postnatal development.

PMID- 14643011
TI  - Spatial and temporal patterns of expression of Noggin and BMP4 in embryonic and
      postnatal rat hippocampus.
AB  - Recent studies indicate that bone morphogenetic protein-4 (BMP4) and Noggin not
      only play an important role in the early development of the nervous system, but
      may also play a role in postnatal central nervous system (CNS) development. In
      this study, we examined the relative levels and localization of Noggin and BMP4
      mRNA in the hippocampus of rats of different developmental stages with reverse
      transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH).
      RT-PCR showed that the temporal changes in the levels of expression of Noggin and
      BMP4 were different. The peak level of expression of Noggin mRNA was observed at
      embryonic day 13 (E13), subsequently gradually declined at 1-3 months (P1-3M)
      postnatal, and was detected only at a low level at P18M. In contrast, the
      expression of BMP4 mRNA increased gradually during embryonic development, reached
      a maximal level at 3 weeks (W) postnatal, and declined only slightly through
      P18M. In situ hybridization revealed that at embryonic stages, Noggin mRNA was
      localized throughout all hippocampal regions, whereas at early postnatal ages,
      Noggin mRNA was primarily localized in the anterior subiculum. At embryonic and
      early postnatal stages, no significant BMP4 mRNA expression was detectable in the
      hippocampus. At later postnatal ages, however, Noggin and BMP4 mRNA expression
      was observed in similar patterns. At 1-3 months postnatal, expression of BMP4 was
      observed mainly in the dentate gyrus and in the CA1-CA3 pyramidal cell layers.
      Lower hybridization signals were observed in the hilus and subiculum. Taken
      together, our results demonstrate that Noggin and BMP4 are expressed in embryonic
      and postnatal hippocampus, and that the temporal and spatial patterns of their
      expression are developmentally regulated. These data suggest that Noggin and BMP4
      play important roles in hippocampal development.

PMID- 14643012
TI  - The sensitivity of sodium channels in immature and mature rat CA1 neurones to the
      local anaesthetics procaine and lidocaine.
AB  - Sodium currents were recorded in CA1 hippocampal cells from new-born (P(4-10))
      and older (P(>22)) rats, using whole-cell voltage clamp techniques. The effects
      of local anaesthetics (procaine and lidocaine) were studied in both cell
      populations. Parameters defining steady-state inactivation, removal of
      inactivation and the affinity of the anaesthetic molecules to the inactivated
      state were determined at both stages of maturation. Procaine and lidocaine
      induced a hyperpolarizing shift in steady-state inactivation curves, and slowed
      the rate of recovery from the inactivated state. Procaine disclosed differences
      between immature and older cells in what concerns block of the closed (resting)
      channels, drug affinity and binding to the inactivated state, i.e. the binding
      rate of procaine was found higher and the affinity lower in younger cells. The
      characteristics of procaine and lidocaine block on CA1 sodium currents differed
      in some particular aspects: magnitude of block on resting channels, shift in the
      voltage dependence and voltage sensitivity of steady-state inactivation, slow
      recovery from inactivation and use-dependent block.

PMID- 14643013
TI  - Quantitative features of the nucleus rotundus in the brain of pre- and post-hatch
      chicks.
AB  - The nucleus rotundus (ROT) is a major relay station in the tectofugal pathway of
      the avian visual system. In this study, some quantitative features of ROT in
      developing chicks were analysed using new stereological methods. Total neuron
      number (N) and mean volume (V) of ROT were estimated by the optical fractionator
      method and by the Cavalieri principle, respectively. Neuronal density of neurons
      in ROT was calculated from these data. The eyes of the chick embryo are not
      normally stimulated by light until days E19/20. Therefore in this study, chicks
      at three developmental stages were investigated: on the 17th embryonic day (E17),
      that is before light stimulation of the visual system, at the time of hatch (0
      day, stimulated by light) and 10 days after hatch (10-day). The results showed
      that N was reduced by 27% between E17 and 0-day, and 7.8% between 0- and 10-day
      while neuronal density was reduced by 15% and 32% over the same periods. It is
      concluded that the reduction of neuronal density during the pre-hatch period may
      be due to neuron loss, whereas the post-hatch decrease of neuronal density may be
      the result of an increase in ROT total volume. Cell loss was more prominent in
      the pre-hatch than in the post-hatch period. Estimates of neuronal density in the
      developing ROT are not useful indicators of developmental status, since they do
      not relate to total neuron number.

PMID- 14643014
TI  - p21ras activation following hypoxia-ischemia in the newborn rat brain is
      dependent on nitric oxide synthase activity but p21ras does not contribute to
      neurologic injury.
AB  - Hypoxia-ischemia (HI) in the perinatal period is associated with significant
      infant mortality and neurologic morbidity. Increase in the activity of nitric
      oxide synthase (NOS) and increased release of nitric oxide (NO) are cardinal
      events in the pathophysiology of stroke and perinatal asphyxia. Cell culture
      studies suggest that the GTP-binding protein p21ras (Ras) is activated by NO in
      an NMDA-receptor-dependent pathway. These findings imply that Ras may be
      activated in vivo by NO released in response to glutamate stimulation during HI.
      The contribution of downstream Ras activation to neurologic injury after
      perinatal HI is unknown. We used a postnatal day 7 rat model of perinatal hypoxia
      ischemia to determine the response of Ras to HI, the role of NO in Ras activation
      and the effect of Ras inhibition on neurologic injury in vivo. Ras is activated
      in both hippocampus and cortex within 2 h after HI. This increase is prevented by
      treatment with the NOS inhibitor, aminoguanidine (AG) and by a farnesyl/protein
      transferase inhibitor, manumycin (MAN). Inhibition of NOS, but not Ras,
      significantly reduces neurologic injury after a 7-day recovery period. This data
      suggests that Ras is activated during the initiation of the cellular response to
      HI in both hippocampus and cortex and that this activation is NO-dependent. Ras
      does not, however, contribute to the pathophysiologic NO-dependent mechanisms of
      neurologic injury in this model.

PMID- 14643015
TI  - Ontogenesis and regulation of cholesterol metabolism in the central nervous
      system of the mouse.
AB  - These studies characterized the ontogenesis and regulation of cholesterol
      turnover in the central nervous system (CNS) of mice. During the first 3 weeks
      after birth, the CNS grew rapidly and equaled 5% of body weight. The cholesterol
      pool in this tissue expanded at a rate of 0.26 mg/day and the CNS synthesized
      sterol at a rate of 0.28 mg/day. In mature mice between 13 and 26 weeks of age,
      there was a marked decrease in these parameters including a reduction in the
      relative size of the CNS to 1.7% of body weight, a decrease in the rate of sterol
      accretion to 0.012 mg/day, and a reduction in the rate of cholesterol synthesis
      to 0.035 mg/day. Deletion of the NPC1 and CYP46A1 proteins markedly altered
      cholesterol metabolism in the CNS. However, changes in the plasma cholesterol
      concentration or loss of function of ATP-binding cassette AI transporter (ABCA1),
      scavenger receptor class B, type I (SR-BI), low-density lipoprotein receptor
      (LDLR), APOE or APOAI had no effect on sterol turnover in the brain. Thus, during
      early development, cholesterol comes entirely from local synthesis. In the adult,
      however, synthesis exceeds the need for structural cholesterol so that there is a
      constant excretion of sterol from the CNS into the plasma at a rate of about
      0.023 mg/day.

PMID- 14643016
TI  - Spatiotemporal patterns of gene expression during fetal monkey brain development.
AB  - Human DNA microarrays are used to study the spatiotemporal patterns of gene
      expression during the course of fetal monkey brain development. The 444 most
      dynamically expressed genes in four major brain areas are reported at five
      different fetal ages. The spatiotemporal profiles of gene expression show both
      regional specificity as well as waves of gene expression across the developing
      brain. These patterns of expression are used to identify statistically
      significant clusters of co-regulated genes. This study demonstrates for the first
      time in the primate the relevance, timing, and spatial locations of expression
      for many developmental genes identified in other animals and provides clues to
      the functions of many unknowns. Two different microarray platforms are used to
      provide high-throughput cross validation of the most important gene expression
      changes. These results may lead to new understanding of brain development and new
      strategies for treating and repairing disorders of brain function.

PMID- 14643017
TI  - Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during
      the differentiation of specific subsets of telencephalic neurons.
AB  - We have performed a screen combining subtractive hybridization with PCR to
      isolate genes that are regulated when neuroepithelial (NE) cells differentiate
      into neurons. From this screen, we have isolated a number of known genes that
      have not previously been associated with neurogenesis, together with several
      novel genes. Here we report that one of these genes, encoding a guanine
      nucleotide exchange factor (GEF), is regulated during the differentiation of
      distinct neuronal populations. We have cloned both rat and mouse GEF genes and
      shown that they are orthologs of the human gene, MR-GEF, which encodes a GEF that
      specifically activates the small GTPase, Rap1. We have therefore named the rat
      gene rat mr-gef (rmr-gef) and the mouse gene mouse mr-gef (mmr-gef). Here, we
      will collectively refer to these two rodent genes as mr-gef. Expression studies
      show that mr-gef is expressed by young neurons of the developing rodent CNS but
      not by progenitor cells in the ventricular zone (VZ). The expression pattern of
      mr-gef during early telencephalic neurogenesis is strikingly similar to that of
      GABA and the LIM homeobox gene Lhx6, a transcription factor expressed by
      GABAergic interneurons generated in the ventral telencephalon, some of which
      migrate into the cortex during development. These observations suggest that mr
      gef encodes a protein that is part of a signaling pathway involved in
      telencephalic neurogenesis; particularly in the development of GABAergic
      interneurons.

PMID- 14643018
TI  - Epigenetic factors differentially influence postnatal maturation of serotonin (5
      HT) innervation in cerebral cortex of gerbils: interaction of rearing conditions
      and early methamphetamine challenge.
AB  - The effects of disjunctive environmental deprivation combined with a single
      methamphetamine (MA) challenge on postnatal maturation of the serotonin (5-HT)
      innervation pattern in cerebral cortex of gerbils were studied. Gerbils were
      assigned to either enriched (ER) or impoverished (IR) environmental rearing
      conditions. On postnatal day 110, 5-HT was immunostained. The 5-HT innervation
      pattern of the brain was qualitatively evaluated and provided in graphic form.
      The densities of 5-HT fibres were quantified in areas of prefrontal, insular,
      frontal, parietal, and entorhinal cortices of the right hemisphere using digital
      image analysis. The early MA challenge led to an overshoot of the fibre density
      in medial and orbital prefrontal cortex and entorhinal cortex of ER animals. IR
      animals mostly resisted MA effects except of a restraint of the innervation of
      the insular cortex. In comparison to enriched rearing, restricted rearing caused
      overshoot maturation of 5-HT innervation in insular and entorhinal cortices. The
      present data provide evidence for a region-specific postnatal vulnerability of
      the maturing 5-HT innervation, namely in association cortices. In contrast, both
      sensory and motor cortices showed no significant changes at all. The results are
      discussed in context with previously presented findings of alterations of the
      cortical dopamine innervation depending on both epigenetic factors. In
      conclusion, both experimental variables together give new insight into raphe
      cortical plasticity that may contribute to a better understanding of the role of
      5-HT fibre systems in structural maturation of the cortex. Postnatal environment
      may be involved in individual vulnerability of a variety of mental disorders
      during adolescence and aging.

PMID- 14643019
TI  - NADPH-diaphorase positivity in the rostral migratory stream of the developing
      rat.
AB  - The NADPH-diaphorase (NADPH-d) histochemical technique is commonly used to
      localize the nitric oxide (NO)-producing enzyme NO synthase (NOS) in neural
      tissues. In this study, we have used NADPH-d histochemistry to examine the spatio
      temporal appearance of nitrergic cells in the rat rostral migratory stream (RMS)
      during postnatal development. The presence of NADPH-d-positive cells was evident
      from postnatal day 10.

PMID- 14643020
TI  - Effects of nicotine infusion on the metabolism of the tobacco carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rats.
AB  - The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is a lung carcinogen in the rat and believed to be a causative agent for
      lung cancer in smokers. To exert its carcinogenic potential NNK is metabolically
      activated by cytochrome P450-catalyzed alpha-hydroxylation. Nicotine and NNK
      share metabolic pathways. The purpose of this study was to determine whether
      nicotine alters the fraction of NNK undergoing activation to carcinogenic
      metabolites. Rats received acute (36 h) or chronic (2 week) s.c. infusions of
      nicotine at rates producing serum nicotine concentrations 2-3 times the usual
      venous nicotine concentrations measured in smokers. A single dose of [5-3H]-NNK
      was administered i.p. 24 h prior to the end of each infusion. Urine was collected
      for 24 h thereafter and NNK metabolites quantified by radioflow HPLC. Neither
      acute nor chronic nicotine infusion had any effect on the extent of NNK
      metabolism by alpha-hydroxylation. These data suggest that nicotine infusion, at
      rates simulating the higher doses of nicotine replacement therapy now being
      studied for smoking cessation, neither induces nor inhibits NNK metabolism
      appreciably and therefore should not alter the formation of carcinogenic NNK
      metabolites.

PMID- 14643021
TI  - Chemopreventive effect of JTE-522, a selective cyclooxygenase-2 inhibitor, on 1,
      2-dimethylhydrazine-induced rat colon carcinogenesis.
AB  - Selective COX-2 inhibitors have been suggested to be an effective strategy in the
      prevention of colon cancer without the adverse side effects of non-selective,
      nonsteroid anti-inflammatory drugs. The present experiment was designed to assess
      the potential chemopreventive properties of JTE-522, a new selective
      cyclooxygenase-2 inhibitor, on the induction of 1,2-dimethylhydrazine (DMH)
      induced colonic aberrant crypt foci (ACF), a marker of rat colon carcinogenesis.
      A total of 80 male F344 rats were treated with 3 or 10 mg/kg of body weight JTE
      522 or vehicle by oral gavage five times weekly from the start of the experiment.
      One week later, rats received s.c. injections of saline or 20 mg/kg of body
      weight DMH once weekly for four successive weeks. At the end of 12 weeks after
      the start of experiment, all rats were sacrificed and colons were evaluated for
      ACF. 10 mg/kg JTE522 significantly suppressed the total ACF/colon. No inhibitory
      effect was observed in the 3 mg/kg JTE-522 treatment group. This result suggests
      that JTE-522 possesses chemopreventive activity against colon carcinogenesis.

PMID- 14643022
TI  - Expression of CYP3A4 in human breast tumour and non-tumour tissues.
AB  - Cytochrome P450 3A4 (CYP3A4), a member of multigene superfamily of enzymes, plays
      a major role in the activation of procarcinogens such as polycyclic hydrocarbon
      dihydrodiols, aflatoxins and heterocyclic amines as well as of several drugs
      including tamoxifen which is used in breast cancer therapy. Using
      immunohistochemistry, the cellular distribution and the level of expression of
      CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast
      tissue in 25 pairs of samples obtained from females with infiltrating ductal
      carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic
      positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of
      normal breast tissues. Cytoplasmic staining was present in invasive ductal
      carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal
      epithelium and myoepithelium. Only focal staining was noted in some of the non
      epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4
      staining was assessed semiquantitatively the mean staining score values of CYP3A4
      were found to be significantly higher in tumours compared to that of normal
      breast tissues. These results show that CYP3A4 protein is expressed in both
      tumour and normal breast tissue with an increased expression in tumours.

PMID- 14643023
TI  - Modulation of doxorubicin sensitivity by a novel organic compound, oxalyl bis (N
      phenyl) hydroxamic acid on acetyl aminofluorene-induced preneoplastic
      hepatocytes.
AB  - Development of biochemical modulators and application of the same with anticancer
      drugs is a current approach of modern cancer chemotherapy. We report the effect
      of two novel hydroxamic acid derivatives, viz. oxaly bis (N-phenyl) hydroxamic
      acid (OBPHA) and succinyl bis (N-phenyl) hydroxamic acid (SBPHA) on doxorubicin
      sensitivity and on P-glycoprotein (P-gp) in acetyl amino fluorene (AAF) induced
      preneoplastic hepatocytes in vitro. OBPHA increases doxorubicin sensitivity in
      AAF induced preneoplastic hepatocytes compared to normal hepatocytes. SBPHA, with
      an additional -CH(2)-CH(2)- group than OBPHA does not modulate the sensitivity of
      doxorubicin. The mechanism of action of OBPHA and SBPHA and their in vivo
      toxicity on male Swiss mice has been studied. OBPHA in combination with
      doxorubicin (i.e. OBPHA+doxorubicin) has higher antitumour activity compared to
      doxorubicin alone group; in consequence, OBPHA may decrease the dose related side
      effect of doxorubicin.

PMID- 14643024
TI  - Protoporphyrin IX-accumulation in human tumor cells following topical ALA- and h
      ALA-application in vivo.
AB  - The fluorescence monitoring represents an innovative approach to detect tumor
      tissue by photosensitizer-mediated fluorescence. Therefore, information on
      cellular uptake, tumor selectivity and accumulation properties of
      photosensitizers are of essential interest. In this study we compared the
      accumulation properties of two photosensitizer precursors, the 5-aminolaevulinic
      acid (ALA) and a hexylester of ALA (h-ALA), in vivo using the hen's egg model and
      the human larynx carcinoma cell line HEp-2. The formation of the actual
      photosensitizer, protoporphyrin IX (PpIX), was determined both qualitatively and
      quantitatively. The intensity of the excited PpIX-fluorescence was observed as an
      indicator for the presence of PpIX after topical ALA- and h-ALA-applications.
      PpIX-fluorescence was measured using spatially resolved fluorescence
      spectroscopy.

PMID- 14643025
TI  - Time and dose-dependent radiosensitization of the glioblastoma multiforme U251
      cells by the EGF receptor tyrosine kinase inhibitor ZD1839 ('Iressa').
AB  - Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes
      unregulated cell growth and inhibits apoptosis, is believed to contribute to
      clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the
      EGFR signalling pathways may offer an attractive therapeutic target to increase
      the cytotoxic effects of radiotherapy. We report the effects of ZD1839
      ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation
      sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In
      radiation survival experiments, 5 microM of ZD1839 had a significant
      radiosensitizing effect and increased cell death was observed at doses of 5Gy in
      the presence of ZD1839. Dose and schedule of drug administration in combination
      with radiation appeared to be a crucial element to obtain radiosensitization of
      the cells. These studies suggest novel therapeutic strategies in the treatment of
      GBM.

PMID- 14643026
TI  - Polymorphisms in prostate-specific antigen (PSA) gene, risk of prostate cancer,
      and serum PSA levels in Japanese population.
AB  - Recent studies have indicated that the prostate-specific antigen (PSA) gene
      polymorphisms may be associated with the risk of prostate cancer in Caucasian
      populations. To verify the association, we examined the PSA polymorphisms at
      positions -158 and -252 in 300 prostate cancer cases, 216 benign prostatic
      hyperplasia (BPH) cases, and 266 controls by the PCR-restriction fragment length
      polymorphism analysis. Regarding the PSA polymorphism at position -158, the A
      allele was less common in the Japanese population (A 0.22, G 0.78) than that in
      other ethnic populations (A 0.37-0.52, G 0.48-0.63). No significant associations
      were found between the polymorphism and the risks of prostate cancer (P=0.530)
      and BPH (P=0.740) and between the polymorphism and the serum PSA level (P=0.626).
      As for the polymorphism at position -252, no significant results were also found.
      In conclusion, the PSA polymorphisms may not be associated with the risk of
      prostate cancer development and its disease progression and the risk of BPH in
      Japanese men, and may also be not related to the serum PSA level in Japanese men
      with prostate cancer.

PMID- 14643027
TI  - Sulfotransferase 1A1 (SULT1A1) polymorphism and bladder cancer risk: a case
      control study.
AB  - Sulfotransferases (SULT) catalyze both the bioactivation and detoxification of a
      wide range of promutagens and procarcinogens. SULT1A1 appears to be an important
      phenol SULT because of its abundance and distribution in many tissues and wide
      substrate specificity. The SULT1A1 gene possesses a G-->A polymorphism that
      results in an Arg to His amino acid substitution, and the His(213) allele has
      been shown to have low activity and low thermal stability. Because of its
      functional role and published data showing the influence of Arg213His
      polymorphism on the risk of some cancers, we hypothesized that the His(213)
      allele of the SULT1A1 gene may modify bladder cancer risk. To test this
      hypothesis, we determined the SULT1A1 Arg213His genotypes in 384 incident bladder
      cancer patients and 386 healthy frequency-matched controls. A comprehensive
      epidemiologic interview was conducted on all participants to collect personal
      information, such as demographics and smoking status. The Arg/His and His/His
      genotypes were more common in the controls than the cases (P=0.035), resulting in
      a His(213) allele frequency of 35.0% in controls and 28.8% in cases. When
      individuals with the His(213) allele genotypes (Arg/His+His/His) were combined
      and compared to individuals with the Arg/Arg genotype, we observed a
      statistically significant reduced risk of bladder cancer (OR=0.72; 95% CI 0.54
      0.97). When we examined the data by gender, there was a statistically significant
      reduced risk of bladder cancer only in women (OR=0.42; 95% CI 0.23-0.78) and not
      in men (OR=0.84; 95% CI 0.60-1.19) with the His(213) genotypes. In addition,
      there was a reduced bladder cancer risk in never smokers (OR=0.59; 95% CI 0.36
      0.98) with the His(213) allele genotypes, but not in former (OR=0.82; 95% CI 0.54
      1.25) or current smokers (OR=0.68; 95% CI 0.29-1.58). The His(213) allele
      genotypes also appeared to provide some protective benefit for current and former
      smokers, as compared to those with the Arg/Arg genotype. In conclusion, this
      study provides epidemiologic evidence of a reduced bladder cancer risk associated
      with the SULT1A1 His(213) polymorphism. Further studies are warranted to
      elucidate the function of this SULT1A1 polymorphism with regard to organ
      specificity, gene-environment interactions, and the gender-related difference we
      observed.

PMID- 14643028
TI  - Alteration of expression or phosphorylation status of tob, a novel tumor
      suppressor gene product, is an early event in lung cancer.
AB  - Tob is a member of the Tob/BTG family, a novel class of anti-proliferative
      proteins. To investigate the involvement of tob as a tumor suppressor gene in
      human lung cancer, we analyzed the expression of tob mRNA and protein in lung
      cancer tissue and adjacent normal lung tissue. Immunohistochemical analysis using
      anti-Tob antibody showed decreased expression of Tob in 72% (31/43) of lung
      cancer tissues. Furthermore, 95% (19/20) of squamous cell carcinoma patients
      showed an apparent decrease in Tob in cancer tissues, associated with smoking
      status. The phosphorylated form of Tob, an inactive form of Tob, was detected in
      76% (16/21) of cancer tissues of adenocarcinoma patients, but not in normal
      alveolar epithelial cells. Either a decrease in Tob expression or an accumulation
      of phosphorylated Tob was observed from early clinical stages, even in bronchial
      dysplasia, a premalignant lesion of squamous cell carcinoma. The above findings
      suggest that the disruption of anti-proliferative Tob plays a distinct part in
      the early stage of lung carcinogenesis.

PMID- 14643029
TI  - Effect of conjugated linoleic acid isomers on growth factor-induced proliferation
      of human breast cancer cells.
AB  - We evaluated the effect of conjugated linoleic acid (CLA) isomers on the growth
      factor-induced proliferation of human breast cancer MCF-7 cells. When MCF-7 cells
      were cultured in RPMI 1640 medium supplemented with 1% fetal bovine serum (FBS),
      CLA inhibited the proliferation and notably cis9, trans11 (c9,t11)-CLA showed the
      strongest effect. However, cells barely grew when cultured with 1% charcoal
      treated FBS (cFBS). Proliferation was promoted in cFBS cultured cells by the
      addition of 17beta-estradiol (E2), insulin, and epidermal growth factor (EGF).
      Trans10, cis12 (T10,c12)-CLA inhibited cell proliferation induced by E2 and
      insulin, but not by EGF. T10,c12-CLA also exhibited cell-killing activity when
      cells were induced with insulin. On the other hand, c9,t11-CLA was shown to have
      no effect on MCF-7 cell proliferation induced by and of these three growth
      factors. In conclusion, although both c9, t11 and t10, c12-CLA can inhibit the
      proliferation of MCF-7 cells, our results suggested that they have separate
      mechanisms and different targets of actions.

PMID- 14643030
TI  - Changes in the number of HSF1 positive granules in the nucleus reflects heat
      shock semiquantitatively.
AB  - PURPOSE: The purpose of this study is to examine the changes in the number of
      HSF1 granules in the nucleus caused by different degree of heat stress. MATERIALS
      AND METHODS: A human esophageal cancer cell line, TE-2, was used. HSF1 granules
      were examined in an immunofluorescence study, and the changes in the average
      number of HSF1 granules after heat alone or heat in combination with KNK437, Hsp
      inhibitor, were evaluated. A band shift of HSF1 was also determined by western
      blot. RESULTS: HSF1 granules appeared soon after the start of heating at 43
      degrees C and reached a peak at 60 min and gradually disappeared after
      discontinuation of heat. In the fractionated heat treatment, preheating (43
      degrees C, 30 min) suppressed the increase in the number of the granules during
      the second heating, but suppression of Hsp72 by KNK437 resulted in increase in
      the number of granules. Continued heating at 43 degrees C with or without KNK437
      maintained the number of the granules at the peak level during heat treatment.
      The band shift of HSF1 examined by western blot correlated with the changes in
      the number of granules. The number of granules also reflected the degree of
      stress according to different temperature. CONCLUSION: The number of HSF1
      granules in the nucleus well reflected heat stress, and was almost consistent
      with phosphorylation of HSF1. The number of HSF1 granules would be a useful tool
      for evaluating different degrees of heat stress semiquantitatively.

PMID- 14643031
TI  - Methylation of ASC/TMS1, a proapoptotic gene responsible for activating
      procaspase-1, in human colorectal cancer.
AB  - ASC/TMS1, a proapoptotic activator of procaspase-1, was reported to be aberrantly
      methylated in human breast cancer. We found that ASC was methylated in three of
      five human colon cancer cell lines lacking ASC protein expression. Demethylation
      treatment of these cell lines lacking ASC with 5-aza-2'-deoxycytidine partially
      restored ASC expression. Methylated ASC was also detected in six of ten
      colorectal cancer tissues. Although clear down-regulation of ASC in the whole
      region of a tumor tissue was hardly observed by immunostaining with anti-ASC mAb,
      complete suppression of ASC was identified in a minor population of the
      colorectal tumor cells. The biological significance of ASC methylation inducible
      ASC suppression in colorectal cancer will be discussed.

PMID- 14643032
TI  - Increased serum levels of interleukin-6 in malnourished patients with colorectal
      cancer.
AB  - Peri-operative serum levels of interleukin-6 (IL-6) were determined in 62
      patients who underwent resection of colorectal cancer to clarify the relationship
      between nutritional status and IL-6 response. Patients were divided into two
      groups based on creatinine height index: malnourished group (n=13) and normally
      nourished group (n=49). The preoperative median serum level of IL-6 in the
      malnourished group was significantly higher than in the normally nourished group
      (P=0.041). The postoperative median serum level of IL-6 in the malnourished group
      also tended to be higher. In conclusion, the peri-operative IL-6 response may be
      activated in malnourished colorectal cancer patients.

PMID- 14643034
TI  - Cervical ripening with oral misoprostol at term.
AB  - OBJECTIVES: To determine the efficacy of 200 microg single dose oral misoprostol
      as a cervical priming agent at term. METHODS: In this double-blind randomized
      trial, 156 pregnant women requiring induction of labor with gestational age of 37
      42 weeks and Bishop score < or =5, were randomized to receive either 200 microg
      of misoprostol or a placebo, orally. Labor was induced with intravenous oxytocin
      infusion 12 h after oral medication if the patient did not go into labor. The
      primary outcome was the change in the Bishop score 12 h after oral medication.
      The secondary outcomes were the timings starting from the drug administration to
      the onset of uterine activity, interval between oral medication and delivery,
      oxytocin need for induction, mode of delivery, frequency of side effects, and
      neonatal and maternal outcome. The chi-square or Fisher exact test, Student's t
      test, and Mann-Whitney U-test were used for analysis of the data. RESULTS: There
      were no significant differences in maternal characteristics or indications of
      induction. The Bishop score 12 h after oral medication significantly improved in
      the misoprostol group compared with the control group [55 (70%)>8 vs. 4 (5%)>8;
      P<0.001]. The induction rate was significantly reduced in the misoprostol group
      (P<0.001). The interval between oral medication and the onset of uterine activity
      was significantly shorter in the misoprostol group (P<0.001). The interval
      between oral medication and delivery was also significantly shorter in the
      misoprostol group (P<0.001). The cesarean delivery rate was significantly lower
      in the misoprostol group (P<0.001). There were no differences between the groups
      with respect to the incidence of tachysystole, hyperstimulation, adverse neonatal
      or maternal outcome. CONCLUSIONS: Oral administration of 200 microg single dose
      of misoprostol is an effective agent not only for cervical priming but also for
      induction of labor at term. Furthermore, it reduces the rate of cesarean
      deliveries.

PMID- 14643035
TI  - Pregnancy outcomes in foreign-born and US-born women.
AB  - OBJECTIVES: To compare pregnancy outcomes between foreign-born women and women
      born in the United States (US-born). METHODS: A retrospective cohort study (1991
      2001) of all deliveries at Grady Memorial Hospital in Atlanta, Georgia. RESULTS:
      Among 49,904 deliveries, 27% were to foreign-born mothers representing 164
      countries grouped into eight geographic regions. Compared with US-born women,
      foreign-born women had a higher mean birthweight (3315 vs. 3083 g), and a lower
      risk of preterm delivery (RR 0.46, 95% CI 0.43-0.49), perinatal mortality (RR
      0.40, 95% CI 0.36-0.45), hypertension (RR 0.31, 95% CI 0.23-0.41), and HIV
      infection (RR 0.13, 95% CI 0.10-0.18). However, foreign-born women had an
      increased risk of diabetes (RR 1.63, 95% CI 1.48-1.79), perineal laceration (RR
      1.71; 95% CI 1.66-1.76), and postpartum hemorrhage (RR 1.10; 95% CI 1.05-1.15).
      CONCLUSIONS: Foreign-born women have better health behaviors, pregnancy outcomes,
      and a lower risk of infectious diseases than US-born women, but they have a
      higher risk of certain medical conditions and obstetric complications.

PMID- 14643036
TI  - Indwelling urinary catheters in cesarean delivery.
AB  - OBJECTIVES: A prospective randomized study was used to determine the effect of
      urinary bladder catheterization on first-void discomfort, time of ambulation,
      hospital stay, and urinary tract infection in women undergoing cesarean delivery.
      METHODS: We randomly assigned 270 women delivered by cesarean section to urinary
      bladder catheterization or no catheterization. Prospective methods were used to
      assess patient discomfort with the first postoperative void after, time of
      ambulation, time of hospital stay, and need for recatheterization. RESULTS: Of
      135 women who did not receive an indwelling urinary catheter after cesarean
      delivery, six (4.4%) patients needed postoperation urinary catheterization. The
      time of first postoperative voiding was 8-11 h in 54 (42.5%) of cases. The
      ambulation time in the uncatheterized group was 6.8 h, vs. 12.9 h in the control
      group. Uncatheterized patients had a shorter hospital stay. Urinary tract
      infection was not assessed in this study. CONCLUSIONS: Routine use of indwelling
      urinary catheter in cesarean delivery patients with a stable hemodynamic
      condition is not necessary.

PMID- 14643037
TI  - Laparoscopic oxidized cellulose (Surgicel) application for small uterine
      perforations.
AB  - OBJECTIVES: To test the efficacy and safety of laparoscopic oxidized cellulose
      application at the uterine perforation site. METHODS: In a prospective study over
      a 3.5-year period a total of 30 women undergoing combined surgical termination of
      pregnancy and laparoscopic sterilization who had a small uterine perforation were
      recruited. Oxidized cellulose (Surgicel) was inserted and attached to the
      perforation site with a laparoscope. The end point was sealing of the perforation
      and complete hemostasis. Laparotomy was performed if hemostasis was not achieved.
      RESULTS: The mean age, parity and gestation were 31.4 years, 3.8 and 9.3 weeks.
      The perforations occurred in the fundal region (60%), anterior wall (16.7%),
      posterior wall (13.3%), upper lateral wall (3.3%) and lower lateral wall (6.7%).
      Mean size of perforations, respectively according to site were 4.3 mm, 3.2 mm,
      3.4 mm, 3 mm and 3.5 mm in the five groups. Laparoscopic oxidized cellulose
      application was successful in all women with fundal, anterior, posterior and
      upper lateral uterine wall perforations. In two women with perforations on the
      lower lateral wall, due to excessive blood loss, oxidized cellulose fell off;
      laparotomy was performed and hemostasis was achieved with sutures. All 28
      laparoscopically-treated women were discharged on the next day in good condition
      with no complications. CONCLUSIONS: Laparoscopic oxidized cellulose application
      appears to be a safe and effective treatment for small uterine perforations that
      are bleeding moderately.

PMID- 14643038
TI  - Doppler flow and arterial location in ovarian tumors.
AB  - OBJECTIVES: This prospective study investigated the clinical evaluation of
      transvaginal color Doppler ultrasonography in the diagnosis of ovarian tumors.
      METHODS: Transvaginal ultrasonography (morphological assessment, DePriest's
      index) and color Doppler analysis were performed for 31 malignant and 64 benign
      tumors ovarian tumors. Serum tumor markers such as CA125, CA72-4, and STN were
      measured. RESULTS: Sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were as follows: DePriest's index, 90.3%, 73.4%,
      62.2%, 94.0%, 78.9%; CA125, 70.4%, 87.7%, 73.1%, 86.2%, 82.1%; minimum pulsatile
      index combined with detection of location of arterial blood flow, 83.9%, 98.4%,
      96.3%, 92.6%, 93.7%, respectively. In cases where arterial blood flow was
      recognized, malignant tumors had significantly fewer diastolic notches, while
      benign tumors had many diastolic notches. The difference in the presence of
      diastolic notch between malignant and benign tumors was significant (P<0.0004).
      CONCLUSIONS: For diagnosis of ovarian tumors, transvaginal color Doppler analysis
      combined with detection of arterial location is more useful than other
      procedures.

PMID- 14643040
TI  - Induction of labor with vaginal misoprostol for second trimester termination of
      pregnancy in the scarred uterus.
AB  - OBJECTIVES: To assess the safety of vaginal misoprostol for second trimester
      pregnancy termination in patients with a history of cesarean section. METHODS: A
      consecutive series of 593 women with pregnancies of 14-26 weeks were studied. A
      cohort of 56 cases had undergone previous cesarean section delivery. The 528
      cases who had no history of prior uterine surgery served as the controls. The
      termination was carried out according to the regimen used at the time of
      enrollment, either 600 microg applied at every 6 or every 12 h, or 800 microg
      applied at every 12 h using the vaginal route. RESULTS: The median induction to
      abortion time in the previous cesarean section group (15.1 h) was not
      significantly different from that of the controls (15.8 h). The median total
      dosage of misoprostol used was the same for both groups (1200 microg). The rates
      of incomplete abortion and analgesia usage were significantly higher in the
      previous cesarean section group as compared with the controls. CONCLUSIONS:
      Vaginal misoprostol was effective for the second trimester pregnancy termination
      but the safety of misoprostol in the scarred uterus cannot be assumed from this
      study. A large series is needed to reach the power to see the difference.

PMID- 14643039
TI  - Dysmenorrhea treatment with a single daily dose of rofecoxib.
AB  - OBJECTIVES: To investigate the efficacy of single daily doses of rofecoxib, a
      selective inhibitor of cyclooxygenase-2, in dysmenorrhea. METHODS: Fifty-five
      patients were included in this randomized, placebo-controlled, cross-over study.
      Patients were randomized to use placebo, naproxen sodium (550 mg), 25 and 50 mg
      doses of rofecoxib in various orders. Pain intensity, analgesic efficacy of
      drugs, total number of pills used and side effects were evaluated. RESULTS:
      Rofecoxib with daily single doses of 25 and 50 mg decreased the pain intensity in
      a manner similar to naproxen sodium. Most of the patients (85.45% and 96.46%)
      evaluated the analgesic efficacy of rofecoxib as 'perfectly effective'. Rofecoxib
      was found to be effective for pain relief both in primary and secondary
      dysmenorrhea. Gastrointestinal adverse effects were less than those with naproxen
      sodium. CONCLUSIONS: A 'one a day' dose of 25 mg rofecoxib is an effective choice
      with lower gastrointestinal adverse effects than naproxen sodium.

PMID- 14643041
TI  - Complications of cervical cerclage in women with cervical incompetence.

PMID- 14643042
TI  - Maternal mortality in the last decade at a university hospital in Turkey.

PMID- 14643043
TI  - Epidural analgesia for painful myomas refractory to medical therapy during
      pregnancy.

PMID- 14643044
TI  - Oral tinidazole treatment during pregnancy and teratogenesis.

PMID- 14643045
TI  - Albumin in vaginal fluid is a marker of infection in early pregnancy.

PMID- 14643046
TI  - Venous thromboembolism in pregnancy and the puerperium in Sudanese women.

PMID- 14643047
TI  - HPV testing and visual inspection for cervical cancer screening in resource-poor
      regions.

PMID- 14643048
TI  - Knowledge, attitudes and practices of rural women in South Africa regarding the
      Pap smear.

PMID- 14643049
TI  - Granulocyte-macrophage colony stimulating factor prior to chemotherapy for
      advanced epithelial ovarian cancer.

PMID- 14643050
TI  - Magnetic resonance imaging in sclerosing stromal tumor of the ovary.

PMID- 14643051
TI  - Intimate partner violence among infertile women.

PMID- 14643052
TI  - Female sexual assault in Nigeria.

PMID- 14643053
TI  - An audit of the management of induced abortion in England and Wales.
AB  - OBJECTIVES: To assess the quality of care provided to women undergoing induced
      abortion. METHODS: The design was a single round audit questionnaire aimed at the
      providers of abortion services throughout England and Wales (NHS hospitals,
      clinics under NHS, agency agreements and private units. The levels of care were
      assessed against agreed audit criteria. RESULTS: Responses were received from 240
      (74%) of the 324 units providing abortion care in England and Wales. These units
      undertook 80% of the 176,000 termination procedures. Generally standards of care
      were appropriate, but there were clear areas for improvement including choice of
      method, infection screening, and delays in referral. A number of unnecessary
      investigations were still evident, including cross-matching, while lower doses
      and alternative drug regimens might reduce costs. Only half of the units audited
      procedures and complications. CONCLUSIONS: This audit was carried out prior to
      the publication of the RCOG evidence-based guideline and a further round of audit
      to assess the impact of the guideline should now be considered.

PMID- 14643054
TI  - Unmet need for contraception in Kuwait: a developing country without a family
      planning program.

PMID- 14643055
TI  - Conversion from white to brown adipocytes: a strategy for the control of fat
      mass?
AB  - Understanding the mechanisms governing the acquisition of white and brown
      adipocyte phenotypes might have implications for the physiopathology of, and
      therapeutic strategies for obesity. Peroxisome proliferator-activated recetor
      gamma (PPARgamma) and its coactivators, PGC-1alpha and SRC-1, influence brown
      adipocyte metabolism and development. Ectopic expression of PGC-1alpha induces
      the expression of brown adipocyte genes in human white adipocytes. The changes in
      gene expression promote stimulation of fatty acid oxidation. There is now
      evidence to support the concept of an alteration in energy balance through a
      conversion of white to brown adipose tissue.

PMID- 14643056
TI  - At the crossroads of skeletal responses to estrogen and exercise.
AB  - The recent observation that mice deficient in estrogen receptor alpha (ERalpha)
      have an impaired response to mechanical strain suggests that ERalpha plays an
      important role in mediating the response of the skeleton to mechanical loading as
      well as to estrogen. In view of previous findings that estrogen deficiency leads
      to a fall in ERalpha numbers, postmenopausal bone loss might result from the
      impaired response of bone to mechanical strain caused by deficient ERalpha
      signalling.

PMID- 14643057
TI  - Is aldosterone synthesized in the CNS regulated and functional?
AB  - The enzymes involved in the synthesis of aldosterone are also expressed in areas
      other than the adrenal gland, including the brain. Aldosterone acts in the brain
      to produce several cardiovascular effects, some of which might result from
      aldosterone that is synthesized locally and that acts in a paracrine or autocrine
      manner. Ye and co-workers recently showed that the mRNA expression of the genes
      for the last enzyme of the aldosterone pathway, aldosterone synthase, is
      regulated by sodium depletion, as is the case in the adrenal gland. However, the
      message for aldosterone synthase in the brain is not increased by chronic
      angiotensin II stimulation or decreased by a high sodium diet, as it is in the
      adrenal gland. This suggests that aldosterone produced in the brain has
      regulatory implications different to those of the circulating steroid and thus
      its regulation is different.

PMID- 14643059
TI  - The role of leptin receptor signaling in feeding and neuroendocrine function.
AB  - The adipose-derived hormone leptin regulates energy balance and neuroendocrine
      function, and resistance to its appetite-suppressing effects might underlie
      common forms of obesity. Understanding the intracellular signaling pathways and
      hypothalamic neural circuitry by which leptin controls satiety and body weight is
      central to our understanding of leptin resistance and the identification of
      potential therapeutic targets. Here, we review the mechanisms by which leptin
      activates intracellular signaling and the roles of two specific leptin-activated
      signals [phosphatidylinositol 3-kinase and signal transducer and activator of
      transcription-3 (STAT3)] in the regulation of body weight and neuroendocrine
      function. The pathway by which leptin activates STAT3 is particularly intriguing
      because it is crucial for the regulation of feeding but dispensable for the
      control of reproductive and growth axes.

PMID- 14643060
TI  - On the association of succinate dehydrogenase mutations with hereditary
      paraganglioma.
AB  - Hereditary paraganglioma (PGL) is characterized by the development of slow
      growing, highly vascularized tumors that can present either as hormonally silent
      head and neck tumors or as abdominal pheochromocytomas. PGL tumors are caused by
      germline inactivating heterozygous mutations in the SDHB, SDHC and SDHD genes,
      which encode three of the four subunits of succinate dehydrogenase (SDH;
      succinate:ubiquinone oxidoreductase; mitochondrial complex II). Here, potential
      mechanisms by which SDH mutations could lead to tumor development are discussed.
      Mechanisms that lead to variations in the prevalence, penetrance and expressivity
      of SDH subunit mutations remain to be clarified to improve the clinical
      management of PGL patients. Recently, germline mutations in the FH gene, the
      product of which (fumarate hydratase) catalyzes the conversion of fumarate to
      malate in the Krebs cycle, have been detected in a distinct hereditary tumor
      syndrome, which is characterized by uterine and skin leiomyomatosis and papillary
      renal cancer. Although the exact mechanisms of tumorigenesis in both disorders
      are unknown, SDH and FH could be involved in the control of cell proliferation
      under normal physiological conditions in the affected tissue types. Whereas SDH
      might be involved in hypoxic proliferation of paraganglia, FH might play an
      important role in the regulation of ammonium metabolism in smooth muscle cells.

PMID- 14643061
TI  - New organs from our own tissues: liver-to-pancreas transdifferentiation.
AB  - Recent advances in pancreatic islet transplantation emphasize the potential of
      this approach for the long-term control of blood glucose levels in diabetic
      patients. However, tissue-replacement therapy will become widely available as a
      treatment for diabetes only when new sources of islets and insulin-producing
      cells are found. Here, we review recent evidence that documents the potential of
      mature liver as a source of tissue for generating a functional endocrine
      pancreas, by ectopic expression of pancreatic transcription and differentiation
      factors. When key events in the transconversion process have been identified,
      using the liver as a source of pancreatic tissue might provide a valuable
      approach for replacing impaired beta cell function in diabetics.

PMID- 14643062
TI  - SR-BI and cholesterol uptake into steroidogenic cells.
AB  - Scavenger receptor class B, type I (SR-BI) is a receptor for high-density
      lipoprotein (HDL) that mediates cellular uptake of HDL cholesteryl ester (HDL CE)
      and is the major route for cholesterol delivery to the steroidogenic pathway. SR
      BI is localized in specialized microvillar channels in the plasma membrane that
      retain HDL and are sites of selective uptake of HDL CE. The formation of
      microvillar channels in the adrenal gland requires SR-BI and is regulated by
      adrenocorticotropin hormone. SR-BI-mediated uptake of HDL CE is a two-step
      process that requires high-affinity binding of HDL followed by transfer of CE to
      the membrane. CE uptake is followed by hydrolysis to free cholesterol by a
      neutral CE hydrolase. In this review, we describe new information on the
      mechanism of transfer of cholesterol from plasma HDL to the steroidogenic pathway
      in endocrine cells.

PMID- 14643063
TI  - Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans.
AB  - In humans, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-HSD and 5alpha
      reductase activities in androgen target tissues, such as the prostate and skin,
      convert dehydroepiandrosterone, androstenedione and testosterone into the most
      potent natural androgen dihydrotestosterone (DHT). This androgen is converted
      mainly in situ into two phase I metabolites, androsterone (ADT) and androstane
      3alpha,17beta-diol (3alpha-DIOL), which might be back converted to DHT. Here, we
      discuss the recent findings regarding the characterization of specific UDP
      glucuronosyltransferases (UGTs), UGT2B7, B15 and B17, responsible for the
      glucuronidation of these metabolites. The tissue distribution and cellular
      localization of the UGT2B transcripts and proteins in humans clearly indicate
      that these enzymes are synthesized in androgen-sensitive tissues. It is
      postulated that the conjugating activity of UGT enzymes is the main mechanism for
      modulating the action of steroids and protecting the androgen-sensitive tissues
      from deleteriously high concentrations of DHT, ADT and 3alpha-DIOL.

PMID- 14643065
TI  - Brain imaging in stuttering: where next?

PMID- 14643066
TI  - Stuttering: a dynamic motor control disorder.
AB  - The purpose of this review is to determine what neural mechanisms may be
      dysfunctional in stuttering. Three sources of evidence are reviewed. First,
      studies of dynamic inter-relationships among brain regions during normal speech
      and in persons who stutter (PWS) suggest that the timing of neural activity in
      different regions may be abnormal in PWS. Second, the brain lesions associated
      with acquired stuttering are reviewed. These indicate that in a high percentage
      of cases, the primary speech and language regions are not affected but lesions
      involve other structures, such as the basal ganglia, which may modulate the
      primary speech and language regions. Third, to characterize the motor control
      disorder in stuttering, similarities and differences from focal dystonias such as
      spasmodic dysphonia (SD) and Tourette's syndrome (TS) are reviewed. This review
      indicates that the central control abnormalities in stuttering are not due to
      disturbance in one particular brain region but rather a system dysfunction that
      interferes with rapid and dynamic speech processing for production. EDUCATIONAL
      OBJECTIVES: The reader will be able to describe: (1) the similarities and
      differences between stuttering and other speech motor control disorders, (2)
      which brain lesions are most likely to produce acquired stuttering in adults, and
      (3) what type of brain abnormality most likely underlies stuttering.

PMID- 14643067
TI  - Towards a functional neural systems model of developmental stuttering.
AB  - This paper overviews recent developments in an ongoing program of brain imaging
      research on developmental stuttering that is being conducted at the University of
      Texas Health Science Center, San Antonio. This program has primarily used H(2)15O
      PET imaging of different speaking tasks by right-handed adult male and female
      persistent stutterers, recovered stutterers and controls in order to isolate the
      neural regions that are functionally associated with stuttered speech. The
      principal findings have emerged from studies using condition contrasts and
      performance correlation techniques. The emerging findings from these studies are
      reviewed and referenced to a neural model of normal speech production recently
      proposed by Jurgens [Neurosci. Biobehav. Rev. 26 (2002) 235]. This paper will
      report (1) the reconfiguration of previous findings within the Jurgens Model; (2)
      preliminary findings of an investigation with late recovered stutterers; (3) an
      investigation of neural activations during a treatment procedure designed to
      produce a sustained improvement in fluency; and (4) an across-studies comparison
      that seeks to isolate neural regions within the Jurgens Model that are
      consistently associated with stuttering. Two regions appear to meet this
      criterion: right anterior insula (activated) and anterior middle and superior
      temporal gyri (deactivated) mainly in right hemisphere. The implications of these
      findings and the direction of future imaging investigations are discussed.
      EDUCATIONAL OBJECTIVES: The reader will learn about (1) recent uses of H(2)15O
      PET imaging in stuttering research; (2) the use of a new neurological model of
      speech production in imaging research on stuttering; and (3) initial findings
      from PET imaging investigations of treated and recovered stutterers.

PMID- 14643068
TI  - Common features of fluency-evoking conditions studied in stuttering subjects and
      controls: an H(2)15O PET study.
AB  - We used H(2)15O PET to characterize the common features of two successful but
      markedly different fluency-evoking conditions -- paced speech and singing -- in
      order to identify brain mechanisms that enable fluent speech in people who
      stutter. To do so, we compared responses under fluency-evoking conditions with
      responses elicited by tasks that typically elicit dysfluent speech (quantifying
      the degree of stuttering and using this measure as a confounding covariate in our
      analyses). We evaluated task-related activations in both stuttering subjects and
      age- and gender-matched controls. Areas that were either uniquely activated
      during fluency-evoking conditions, or in which the magnitude of activation was
      significantly greater during fluency-evoking than dysfluency-evoking tasks
      included auditory association areas that process speech and voice and motor
      regions related to control of the larynx and oral articulators. This suggests
      that a common fluency-evoking mechanism might relate to more effective coupling
      of auditory and motor systems -- that is, more efficient self-monitoring,
      allowing motor areas to more effectively modify speech. These effects were seen
      in both PWS and controls, suggesting that they are due to the sensorimotor or
      cognitive demands of the fluency-evoking tasks themselves. While responses seen
      in both groups were bilateral, however, the fluency-evoking tasks elicited more
      robust activation of auditory and motor regions within the left hemisphere of
      stuttering subjects, suggesting a role for the left hemisphere in compensatory
      processes that enable fluency. EDUCATIONAL OBJECTIVES: The reader will learn
      about and be able to: (1) compare brain activation patterns under fluency- and
      dysfluency-evoking conditions in stuttering and control subjects; (2) appraise
      the common features, both central and peripheral, of fluency-evoking conditions;
      and (3) discuss ways in which neuroimaging methods can be used to understand the
      pathophysiology of stuttering.

PMID- 14643069
TI  - Preliminary results of a functional MRI study of brain activation patterns in
      stuttering and nonstuttering speakers during a lexical access task.
AB  - An fMRI study examining lexical access and lexical generation in nine non
      stuttering and seven stuttering speakers is presented. Lexical access was
      examined during a word description task that was presented auditorily while
      subjects "silently" thought of the target words. Participants alternated between
      four 30-s rest blocks and four 30-s "active" blocks. Activation patterns were
      assessed utilizing a standard subtraction paradigm, where the activation during
      the rest blocks was subtracted from the activation during the active blocks. High
      levels of variability characterized activation patterns within both speaker
      groups. Group comparisons using random effects statistical analyses did not
      identify significant differences between the groups when corrected for multiple
      comparisons. Analyses were subsequently conducted by comparing the trends in the
      group activation patterns between the speaker groups using fixed (corrected) and
      random effects (uncorrected) analyses. Non-stuttering control speakers activated
      primarily left hemisphere cortical speech and language areas while the stuttering
      speakers appeared to produce more bilateral activation. Discussion of these
      results focuses on the specific within- and between-hemispheric activation
      patterns and possible interpretations of these patterns. EDUCATIONAL OBJECTIVES:
      The reader will learn about: (1) issues related to interpreting brain activation
      findings in stuttering speakers; (2) the role and neurological substrates of
      lexical access during speech production in non-stuttering and stuttering
      speakers; (3) the basics of functional MRI; and (4) the brain activation areas
      involved during a silent lexical retrieval task in non-stuttering and stuttering
      speakers.

PMID- 14643070
TI  - A positron emission tomography study of short- and long-term treatment effects on
      functional brain activation in adults who stutter.
AB  - Previous studies have shown that fluency-inducing techniques, such as choral
      speech, result in changes in neural activation as measured by functional
      neuroimaging. In the present study, positron emission tomography was used to
      investigate the effects of intensive behavioural treatment, followed by a 1-year
      maintenance program, on the pattern of cortical and subcortical activation in
      stuttering adults during silent and oral reading of single words. The results
      indicate changes in activation lateralisation, as well as a general reduction in
      over-activation, especially in the motor cortex, following treatment. The results
      are discussed in light of previous functional imaging studies with stuttering
      adults. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to
      describe the: (1) use of functional neuroimaging PET in the study of stuttering;
      (2) differences in neural activation between stuttering and non-stuttering
      adults; and (3) effects of behavioural fluency treatment on cortical and
      subcortical activations in stuttering speakers.

PMID- 14643071
TI  - The nature and treatment of stuttering as revealed by fMRI A within- and between
      group comparison.
AB  - This article reviews some of our recent functional magnetic resonance imaging
      (fMRI) studies of stuttering. Using event-related fMRI experiments, we
      investigated brain activation during speech production. Results of three studies
      comparing persons who stutter (PWS) and persons who do not stutter (PWNS) are
      outlined. Their findings point to a region in the right frontal operculum (RFO)
      that was consistently implicated in stuttering. During overt reading and before
      fluency shaping therapy, PWS showed higher and more distributed neuronal
      activation than PWNS. Immediately after therapy differential activations were
      even more distributed and left sided. They extended to frontal, temporal, and
      parietal regions, anterior cingulate, insula, and putamen. These over-activations
      were slightly reduced and again more right sided two years after therapy. Left
      frontal deactivations remained stable over two years of observation, and
      therefore possibly indicate a dysfunction. After therapy, we noted higher
      activations in persons who stutter moderately than in those who stutter severely.
      These activations might reflect patterns of compensation. We discuss why these
      findings suggest that fluency-inducing techniques might synchronize a disturbed
      signal transmission between auditory, speech motor planning, and motor areas.
      EDUCATIONAL OBJECTIVES: The reader will learn about and be able to: (1) identify
      regions of brain activations and deactivations specific for PWS; (2) describe
      brain activation changes induced by fluency shaping therapy; and (3) discuss the
      correlation between stuttering severity and brain activation.

PMID- 14643072
TI  - Brain imaging and stuttering: some reflections on current and future
      developments.

PMID- 14643073
TI  - Overview of the DIG trial.
AB  - Congestive heart failure is a major public health problem in the United States,
      Canada, and other Western countries. The Digitalis Investigation Group (DIG)
      trial was a randomized, double-blind placebo-controlled trial that evaluated the
      effects of digoxin on all-cause mortality and on hospitalization for heart
      failure in patients with heart failure and left ventricular ejection fraction <
      or =0.45 with normal sinus rhythm. It was designed as a large simple trial. There
      were 6800 patients entered into the main study over a 31.5-month recruitment
      period at 302 participating centers in the United States and Canada. All patients
      were followed for a minimum of 28 months. In order for this study to succeed,
      many groups had to work together successfully. In this supplement, we present
      practical aspects of organizing and conducting a large simple trial such as DIG.

PMID- 14643074
TI  - The role of the data coordinating center in the DIG trial.
AB  - The Digitalis Investigation Group (DIG) trial was a large simple trial (LST)
      begun in 1990 as a collaboration between the National Heart, Lung, and Blood
      Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program
      (CSP). Its primary objective was to determine whether digitalis had beneficial,
      harmful, or no effect on total mortality in patients with congestive heart
      failure and an ejection fraction < or =0.45. The Perry Point VA CSP Coordinating
      Center served as the trial's data coordinating center (DCC). The DCC was involved
      in all phases of the study from planning and design, organization and start-up,
      and patient recruitment and follow-up through closeout, final analyses, and
      manuscript preparation. While DCC responsibilities for an LST are basically the
      same as for other multicenter randomized clinical trials, their size and the
      inclusion of many inexperienced research sites can add a complexity that the DCC
      must be prepared to handle from the beginning. This paper describes the role of
      the DCC in the DIG trial.

PMID- 14643075
TI  - The role of the pharmacy coordinating center in the DIG trial.
AB  - Large simple trials (LSTs) emerged in response to the need for large sample sizes
      to answer important clinical questions in which treatments have a moderate effect
      on clinical endpoints. Between 1991 and 1996 the National Heart, Lung, and Blood
      Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program
      conducted an LST entitled "Digitalis Investigation Group (DIG): Trial to Evaluate
      the Effect of Digitalis on Mortality in Heart Failure." The VA Cooperative
      Studies Program Clinical Research Pharmacy Coordinating Center served as the DIG
      pharmacy coordinating center (PCC). As a direct result of involvement in the DIG
      trial, the PCC identified the need for an increased emphasis on computerization
      and automated support of clinical trials, especially LSTs.

PMID- 14643076
TI  - The use of regional coordinating centers in large clinical trials: the DIG trial.
AB  - The Digitalis Investigation Group (DIG) trial was a large simple clinical trial
      that involved 302 participating centers in the United States and Canada. In order
      to encourage participation by Canadian investigators, to provide additional help
      to what were expected to be largely research-inexperienced investigators in
      Canada, and to provide the study's data coordinating center with resources in
      Canada to deal with potentially different rules, regulations, and cultural
      differences, regional coordinating centers were established in four regions of
      Canada: the maritime provinces, Quebec, Ontario, and western Canada. Canadian
      centers recruited significantly better than their U.S. counterparts and had
      slightly better retention and follow-up. While it is not possible to declare that
      the regional coordinating centers were responsible for this improvement, it is
      believed that these regional centers did play a role. This role included being
      able to identify investigators who could be expected to do well, providing one-on
      one training and instruction to investigators, and being able to solve problems
      and implement change in the relatively fewer centers in their regions. The
      regional coordinating center also reduced the intensity of the workload on the
      data coordinating center by serving as the primary point of contact for Canadian
      investigators. The use of regional coordinating centers in studies with a large
      number of participating centers is highly recommended.

PMID- 14643077
TI  - The role of the data coordinating center in the IRB review and approval process:
      the DIG trial experience.
AB  - Before any clinical trial can begin to recruit patients, participating clinical
      centers must obtain approval from their institutional review board (IRB). When
      studies are federally funded, such as by the U.S. Department of Health and Human
      Services (DHHS), centers must also have or obtain a federal compliance agreement
      from the Office of Human Research Protections (formerly the Office for Protection
      from Research Risks [OPRR]). The Digitalis Investigation Group trial was a large,
      international, double-blind, DHHS-funded randomized trial on the effect of
      digoxin on mortality in heart failure. Due to the anticipated number of centers
      (>200), the study's data coordinating center (DCC) was requested to assume
      additional responsibilities that included: (1) acting as a liaison between the
      OPRR and all study centers; (2) reviewing and correcting all assurance statements
      before submission to the OPRR; (3) reviewing and approving all centers' informed
      consent forms; and (4) helping the many research-inexperienced centers to
      establish IRBs or to locate an IRB in their region that would accept IRB
      responsibility for them. Although a heavy burden was placed on the DCC, the IRB
      and OPRR approval process was probably shortened by many weeks at those centers
      not already possessing a federal compliance agreement. This enabled the study to
      be completed on schedule and within budget.

PMID- 14643078
TI  - Lessons learned from the DIG trial.
AB  - The Digitalis Investigation Group (DIG) trial was the first large simple trial
      conducted by the National Heart, Lung, and Blood Institute in conjunction with
      the Department of Veterans Affairs. A large simple trial is a major undertaking.
      Simplification at the sites requires careful planning and discipline. Lessons
      learned from the DIG trial were: (1) keep a large simple trial very simple and
      keep all study procedures very simple; (2) ancillary studies are important and
      can complement a large simple trial but require careful advanced planning; (3)
      anticipate special needs when shipping study drugs internationally; (4) regional
      coordinating centers can be very useful; (5) recruit as many capable sites as
      possible; (6) provide research-inexperienced sites/investigators with extra help
      to obtain federalwide assurance statements from the Office for Human Research
      Protections and institutional review board approvals; (7) adequately reimburse
      sites for the work completed; (8) maintain investigator enthusiasm; (9) monitor
      the slow performers and sites with numerous personnel changes; (10) choose an
      endpoint that is easy to ascertain; (11) keep the trial simple for participants;
      and (12) plan early for closeout and for activities between the end of the trial
      and publication of results.

PMID- 14643079
TI  - Using conditional mutagenesis to study the brain.
AB  - Conditional genetic modifications are used to determine how individual molecules
      contribute to the function of defined neuronal circuits in the mouse brain. Among
      various techniques for these genetic modifications, the tetracycline
      transactivator and the Cre-loxP systems have proved to be most successful in
      recent years. Here we describe the basic principles, recent developments, and
      potential applications of these methodologies. We discuss their impact on the
      study of general brain function and their use for modeling different brain
      disorders.

PMID- 14643080
TI  - Automatic activation of the semantic network in schizophrenia: evidence from
      event-related brain potentials.
AB  - BACKGROUND: Language disorder associated with schizophrenia might be due to
      disturbances in both automatic activation and mechanisms of controlled attention.
      The contribution of each process to semantic memory dysfunction has not been
      determined for schizophrenia, and the semantic priming paradigm is well-suited
      for addressing this question. In the present report, event-related potentials
      (ERPs) elicited under conditions assumed to reveal automatic activation (short
      prime-target interval and low proportion of related words) are compared directly
      with ERPs elicited under conditions associated with controlled processing (long
      prime-target interval and high proportion of related words). METHODS: Visual ERPs
      were recorded during a lexical decision task, in which semantic relationship
      (associated and unassociated words), expectancy (relatedness proportions), and
      prime-target interval (250- and 850-msec inter-stimulus intervals [ISIs]) were
      varied. Diagnosis and expectancy were between-subjects factors; semantic
      relationship and ISI were repeated measures. The N400 priming effect (enhanced
      negativity to unassociated words) was compared between 34 male normal control
      subjects tested once and 37 male schizophrenia inpatients evaluated during their
      participation in a double-blind haloperidol maintenance therapy and placebo
      replacement protocol. RESULTS: The N400 priming effect for patients was
      significantly reduced during both pharmacologic phases, compared with controls.
      During haloperidol treatment, however, patients showed a significant N400 priming
      effect over the anterior scalp region and additionally under the automatic
      activation condition. The N400 priming effect was enhanced under the controlled
      processing condition for control subjects; this effect was not observed for
      patients. N400 amplitude elicited under the rapid presentation rate (250-msec
      ISI) differed between medicated patients and controls; groups did not differ for
      the 850-msec ISI. CONCLUSIONS: Findings suggest that automatic activation and
      mechanisms of controlled attention are both disrupted during semantic memory
      access for schizophrenia patients. Pharmacologic agents, such as haloperidol,
      might enhance automatic activation of the semantic network in this patient
      population, as indexed by the N400 component of the ERP.

PMID- 14643081
TI  - Reduced laterality of the source locations for generators of the auditory steady
      state field in schizophrenia.
AB  - BACKGROUND: Reduced hemispheric asymmetry of evoked field generators in
      schizophrenia in secondary auditory cortex has been replicated with mixed
      success. This disparity is possibly due to the complex nature of the 100-msec
      generators typically investigated. In this study, we evaluated a source located
      in primary auditory cortex, responsible for the steady-state response, to
      determine whether similar asymmetries were present. METHODS: Contralateral evoked
      fields were recorded with a 37-channel neuromagnetometer in response to 40-Hz
      pulse trains. Dipole models were used to localize the sources in both hemispheres
      of schizophrenic subjects (n = 17) and normal control subjects (n = 18). RESULTS:
      Control subjects were asymmetrically lateralized, with sources in the right
      hemisphere approximately 6 mm further anterior than those on the left. In
      contrast, schizophrenic subjects showed no significant difference between
      hemispheres. CONCLUSIONS: The findings support theories linking schizophrenia to
      disturbed asymmetry of temporal lobe function. The steady-state response, having
      a more discrete Heschl's gyrus generator location, may be better suited for
      evaluating auditory asymmetry.

PMID- 14643082
TI  - Levels-of-processing effect on word recognition in schizophrenia.
AB  - BACKGROUND: Individuals with schizophrenia have difficulty organizing words
      semantically to facilitate encoding. This is commonly attributed to
      organizational rather than semantic processing limitations. By requiring
      participants to classify and encode words on either a shallow (e.g.,
      uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of
      processing paradigm eliminates the need to generate organizational strategies.
      METHODS: This paradigm was administered to 30 patients with schizophrenia and 30
      healthy comparison subjects to test whether providing a strategy would improve
      patient performance. RESULTS: Word classification during shallow and deep
      encoding was slower and less accurate in patients. Patients also responded slowly
      during recognition testing and maintained a more conservative response bias
      following deep encoding; however, both groups showed a robust levels-of
      processing effect on recognition accuracy, with unimpaired patient performance
      following both shallow and deep encoding. CONCLUSIONS: This normal levels-of
      processing effect in the patient sample suggests that semantic processing is
      sufficiently intact for patients to benefit from organizational cues. Memory
      remediation efforts may therefore be most successful if they focus on teaching
      patients to form organizational strategies during initial encoding.

PMID- 14643083
TI  - Prepulse inhibition deficits of the startle reflex in neonatal ventral
      hippocampal-lesioned rats: reversal by glycine and a glycine transporter
      inhibitor.
AB  - BACKGROUND: Neonatal ventral hippocampal (NVH) lesions in rats induce behavioral
      abnormalities at adulthood thought to simulate some aspects of the positive,
      negative, and cognitive deficits classically observed in schizophrenic patients.
      Such lesions induce a postpubertal emergence of prepulse inhibition (PPI)
      deficits of the startle reflex reminiscent of the sensorimotor gating deficits
      observed in a majority of schizophrenic patients. To study the potential
      involvement of the glycinergic neurotransmission in such deficits, we
      investigated the capacity of glycine (an obligatory N-methyl-D-aspartate [NMDA]
      receptor co-agonist) and ORG 24598 (a selective glycine transporter 1 inhibitor)
      to reverse NVH lesion-induced PPI deficits in rats. METHODS: Ibotenic acid was
      injected bilaterally into the ventral hippocampus of 7-day-old pups. Prepulse
      inhibition of the startle reflex was measured at adulthood. RESULTS: Glycine (.8
      and 1.6 g/kg IP) and ORG 24598 (10 mg/kg IP) fully and partially reversed lesion
      induced PPI deficits, respectively. CONCLUSIONS: These findings confirm that an
      impaired glutamatergic neurotransmission may be responsible for PPI deficits
      exhibited by NVH-lesioned rats and support the hypoglutamatergic hypothesis of
      schizophrenia. They also suggest that drugs acting either directly at the NMDA
      receptor glycine site or indirectly on the glycine transporter 1 could offer
      promising targets for the development of novel therapies for schizophrenia.

PMID- 14643085
TI  - Functional and effective frontotemporal connectivity and genetic risk for
      schizophrenia.
AB  - BACKGROUND: Functional neuroimaging and electrophysiologic studies have found
      disturbed frontotemporal interaction in schizophrenia. We sought to determine
      whether abnormalities of frontotemporal connectivity are trait markers of genetic
      risk for schizophrenia. METHODS: We investigated 64 schizophrenia patients, 79 of
      their clinically unaffected siblings, and 88 unrelated normal controls with an
      auditory oddball electroencephalogram (EEG) evoked potential paradigm. We
      measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of
      functional connectivity); and 2) we performed structural equation modeling of the
      effective connectivity between the frontal P300 and temporoparietal P300
      amplitude. RESULTS: Schizophrenic patients and their siblings showed a reduction
      of frontotemporal coherence. At peak activation during the P300 time-window, a
      negative ("inhibitory") frontotemporal path coefficient was found in normal
      controls, whereas a positive coefficient was seen in schizophrenic patients with
      siblings being intermediate. Intra-class correlations between sib-pairs and
      relative risk estimates of the applied connectivity measures were non
      significant. Topographic correlation matrix analyses suggested that the altered
      functional and effective frontotemporal connectivity indirectly reflect regional
      abnormalities of increased activation variance. CONCLUSIONS: Impaired interaction
      of the frontotemporal macro-circuit indirectly reflects genetically determined
      abnormalities of frontal and temporoparietal microcircuits. The reasons why
      frontotemporal connectivity appears to be a poor predictor of genetic risk for
      schizophrenia are discussed.

PMID- 14643086
TI  - Raclopride studies of dopamine release: dependence on presynaptic integrity.
AB  - BACKGROUND: Raclopride and dopamine (DA) compete for in vivo binding to the D(2)
      receptors. Thus, measurements of raclopride binding provide a method to evaluate
      endogenous release in a variety of conditions. Amphetamine elicits DA release,
      provoking a rapid increase in synaptic DA and leading to a reduction in
      raclopride binding, which outlasts the temporary increase in extracellular DA
      concentrations by several hours. The mechanism responsible for the decrease in
      raclopride binding is still unclear. METHODS: We used a multiple ligand
      concentration receptor assay method in normal monkeys and in monkeys with varying
      degrees of lesion of the DA nigrostriatal terminals to measure the density and
      affinity of D(2) receptors after methamphetamine challenge. RESULTS: The reduced
      raclopride binding can be accounted for by a decreased affinity of the ligand to
      the receptors. There is a direct, nonlinear relationship between the presynaptic
      storage capacity and the change in raclopride binding after methamphetamine.
      CONCLUSIONS: This observation may bear important implications for the
      understanding of diseases such as schizophrenia in which the marked increase in
      amphetamine-induced displacement of raclopride compared with normal control
      subjects suggests increased release of DA from presynaptic stores and potential
      abnormalities in presynaptic DA function.

PMID- 14643084
TI  - Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance
      diffusion tensor imaging study.
AB  - Evidence suggests that a disruption in limbic system network integrity and, in
      particular, the cingulate gyrus (CG), may play a role in the pathophysiology of
      schizophrenia; however, the cingulum bundle (CB), the white matter tract
      furnishing both input and output to CG, and the most prominent white matter fiber
      tract in the limbic system, has not been evaluated in schizophrenia using the new
      technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate
      diffusion in the CB in 16 male schizophrenia patients and 18 male control
      subjects, group-matched for age, parental socioeconomic status, and handedness.
      We acquired 4-mm-thick coronal slices through the entire brain. Maps of
      fractional anisotropy (FA) were generated to quantify diffusion within the left
      and right CB on eight slices that included the central portion of the CB. Results
      showed group differences, bilaterally, in area and mean FA for CB, where patients
      showed smaller area and less anisotropy than controls. For patients, decreased
      left CB correlated significantly with attention and working memory measures as
      assessed by the Wisconsin Card Sorting Test. These data provide strong evidence
      for CB disruptions in schizophrenia, which may be related to disease-related
      attention and working memory abnormalities.

PMID- 14643087
TI  - Do schizotypal symptoms mediate the relationship between genetic risk for
      schizophrenia and impaired neuropsychological performance in co-twins of
      schizophrenic patients?
AB  - BACKGROUND: Neurocognitive deficits and symptoms of schizotypal personality
      disorder are both elevated in the first-degree relatives of schizophrenic
      patients, but their relationship to each other and their potential common genetic
      source remain unclear. METHODS: Fifty unaffected co-twins of schizophrenic
      patients and 123 control twins were assessed with a neuropsychological battery
      and structured clinical interviews. RESULTS: Working memory was influenced by
      genetic risk for schizophrenia but not schizotypal symptoms. Nearly all other
      domains were influenced by schizotypy symptoms but only in the co-twins of
      schizophrenic patients. Schizotypy symptoms in the absence of a family history
      did not seem to be related to impaired neurocognitive functioning. CONCLUSIONS:
      Schizotypy symptoms in those with genetic risk for schizophrenia are associated
      with increased risk for cognitive deficits. Some neurocognitive deficits might
      covary with subpsychotic symptoms due to a shared genetic factor. Community
      ascertained schizotypal individuals might not be appropriate for modeling
      underlying genetic risk for schizophrenia.

PMID- 14643088
TI  - Tumor necrosis factor-alpha gene promoter polymorphisms in chronic schizophrenia.
AB  - BACKGROUND: Alterations in cytokine levels in patients with schizophrenia have
      been documented. Polymorphisms in these cytokine genes are thus potential genetic
      markers for schizophrenia. The aim of this study was to investigate four
      biallelic polymorphisms in the tumor necrosis factor-alpha (TNFalpha) gene
      promoter in relation to susceptibility to schizophrenia. METHODS: Three hundred
      two patients and 152 control subjects were genotyped and frequencies of genotypes
      and alleles were compared for the -1031T/C, -863C/A, -857C/T, and -308G/A
      polymorphisms. Genotype and allele frequencies were compared between controls and
      patients. RESULTS: There were statistically significant differences in genotype
      distribution and allele frequencies for the -308 polymorphism (p <.001). Genotype
      distribution and allele frequencies of the other three polymorphisms were not
      different between patients and reference controls. CONCLUSIONS: The -308
      polymorphism or another genetic variant in linkage disequilibrium with it could
      be a susceptibility factor for chronic schizophrenia.

PMID- 14643089
TI  - Decrease of serotonin receptor 2C in schizophrenia brains identified by high
      resolution mRNA expression analysis.
AB  - BACKGROUND: RNA expression profiling can provide hints for the selection of
      candidate susceptibility genes, for formulation of hypotheses about the
      development of a disease, and/or for selection of candidate gene targets for
      novel drug development. We measured messenger RNA expression levels of 16
      candidate genes in brain samples from 55 schizophrenia patients and 55 controls.
      This is the largest sample so far used to identify genes differentially expressed
      in schizophrenia brains. METHODS: We used a sensitive real-time polymerase chain
      reaction methodology and a novel statistical approach, including the development
      of a linear model of analysis of covariance type. RESULTS: We found two genes
      differentially expressed: monoamine oxidase B was significantly increased in
      schizophrenia brain (p =.001), whereas one of the serotonin receptor genes,
      serotonin receptor 2C, was significantly decreased (p =.001). Other genes,
      previously proposed to be differentially expressed in schizophrenia brain, were
      invariant in our analysis. CONCLUSIONS: The differential expression of serotonin
      receptor 2C is particularly relevant for the development of new atypical
      antipsychotic drugs. The strategy presented here is useful to evaluate
      hypothesizes for the development of the disease proposed by other investigators.

PMID- 14643091
TI  - Hippocampal deformities in the unaffected siblings of schizophrenia subjects.
AB  - BACKGROUND: Neuroanatomical abnormalities have been reported in schizophrenia
      subjects and their relatives and may be related to genetic vulnerability. The
      objective of this study was to further elucidate hippocampal deformities as a
      marker of genetic vulnerability for schizophrenia. METHODS: Magnetic resonance
      scans were collected in 13 pairs of schizophrenics and their unaffected siblings
      from families with multiple affected members, in 12 schizophrenics from families
      without another affected member, and in 10 healthy controls. Hippocampal volume
      and shape were compared using large-deformation high-dimensional brain mapping.
      RESULTS: Decreases in hippocampal volume, covaried for total cerebral volume,
      were observed in the schizophrenia subjects from families with multiple affected
      members, as well as in their unaffected siblings. Shape analysis demonstrated
      that both groups of schizophrenia subjects, as well as the unaffected siblings,
      could be distinguished from the controls; however, no significant difference in
      hippocampal shape was found between the schizophrenia subjects and their
      unaffected siblings. Visualization of the pattern of hippocampal shape deformity
      in both groups of schizophrenia subjects and in the unaffected siblings showed
      inward deformities of the head of the hippocampus. CONCLUSIONS: Deformations of
      hippocampal anatomy may be related to the genetic vulnerability of acquiring
      schizophrenia.

PMID- 14643090
TI  - Dementia rating and nicotinic receptor expression in the prefrontal cortex in
      schizophrenia.
AB  - BACKGROUND: The etiology of dementia that occurs in patients with schizophrenia
      is not well understood. Nicotinic acetylcholine receptors have been implicated in
      cognitive function, and deficits in these receptors have been reported in
      schizophrenia. METHODS: The present study investigates possible associations of
      nicotinic receptor subunit expression in the dorsal lateral prefrontal cortex, an
      area known to be affected in schizophrenia, and dementia rating. RESULTS: alpha7
      immunoreactivity was reduced by 20% to 28% and [(3)H]epibatidine binding was
      increased twofold in groups of patients with schizophrenia compared to normal
      control subjects matched for age, postmortem delay, and low levels of brain
      nicotine and cotinine. In contrast, no significant differences in alpha4, alpha3,
      or beta2 immunoreactivity or alpha7 messenger RNA expression were observed in
      schizophrenia patients compared with control subject values. Clinical dementia
      ratings in patients with schizophrenia were correlated with neither
      [(3)H]epibatidine binding nor nicotinic receptor subunit expression. CONCLUSIONS:
      These data indicate no relationship between the trend for reduced neocortical
      alpha7 subunit protein expression in schizophrenia and dementia. Further
      investigations are required to establish whether the reduction in alpha7 protein
      in the dorsal lateral prefrontal cortex is associated with clinical features
      other than dementia in schizophrenia.

PMID- 14643092
TI  - Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled
      crossover trial.
AB  - BACKGROUND: There is no evidence from randomized, controlled trials that
      demonstrate effectiveness for any pharmacological treatment in clozapine
      resistant schizophrenia. Since the introduction of chlorpromazine, all
      antipsychotics with proven efficacy on positive symptoms have been dopamine
      antagonists, but recent experimental data suggest that ketamine-induced positive
      schizophreniform symptoms in healthy subjects can be controlled by a glutamate
      antagonist lamotrigine. The hypothesis tested was that lamotrigine is more
      effective than placebo in the treatment of positive schizophrenic symptoms when
      combined with clozapine. METHODS: Thirty-four hospitalized treatment-resistant
      patients having chronic schizophrenia participated in a double-blind, placebo
      controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually
      added to their ongoing clozapine treatment. Clinical assessments were made by the
      Positive and Negative Syndrome Scale at the beginning and end of each treatment
      period. RESULTS: In intention-to-treat analysis, lamotrigine treatment was more
      effective in reducing positive (effect size.7, p =.009) and general
      psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was
      observed in negative symptoms. CONCLUSIONS: These results provide the first
      evidence from a randomized controlled trial of an effective pharmacological
      treatment with an anticonvulsant agent in treatment-resistant schizophrenia and
      indicate that both positive and general psychopathological symptoms in patients
      with schizophrenia can be controlled by a drug that is not a dopamine antagonist.
      The results are in line with previous experimental data suggesting that excessive
      glutamate neurotransmission contributes to the positive symptoms of
      schizophrenia.

PMID- 14643093
TI  - Clozapine treatment attenuated somatic and affective signs of nicotine and
      amphetamine withdrawal in subsets of rats exhibiting hyposensitivity to the
      initial effects of clozapine.
AB  - BACKGROUND: Based on the phenomenologic similarity between symptoms of drug
      withdrawal and the negative symptoms of schizophrenia (e.g., anhedonia), we
      hypothesized that treatment with clozapine may be effective against nicotine and
      amphetamine withdrawal. METHODS: A rate-independent discrete-trial threshold
      procedure was used to assess brain stimulation reward in rats prepared with
      electrodes in the lateral hypothalamus. Somatic signs of nicotine withdrawal were
      also assessed. RESULTS: Clozapine administration (.75 or 1.5 mg/kg) during
      nicotine or amphetamine withdrawal did not affect the threshold elevations
      associated with drug withdrawal. The.75 mg/kg clozapine dose reversed the
      increased number of somatic signs of nicotine withdrawal. Ten days of clozapine
      treatment (3 mg/kg/b.i.d.) before exposure to nicotine prevented the threshold
      elevations in a subset of rats and the increases in somatic signs in all
      subjects. Fourteen-day pretreatment with clozapine (6 mg/kg/day) decreased the
      duration of amphetamine withdrawal. CONCLUSIONS: Correlational analyses indicated
      that the ability of clozapine to prevent the affective aspects of drug withdrawal
      depended on low sensitivity to acute clozapine under baseline conditions. The
      results are consistent with the clinical situation where clozapine is partially
      effective against the negative symptoms of schizophrenia and more effective in
      some individuals than others. These results indicate that lack of sensitivity to
      the initial negative effects of clozapine may predict its a subsequent
      therapeutic response. Finally, the data suggest that there may be commonalities
      in the neurosubstrates mediating affective aspects of drug withdrawal and the
      negative symptoms of schizophrenia.

PMID- 14643094
TI  - Genome-wide scan and conditional analysis in bipolar disorder: evidence for
      genomic interaction in the National Institute of Mental Health genetics
      initiative bipolar pedigrees.
AB  - BACKGROUND: In 1989 the National Institute of Mental Health began a collaborative
      effort to identify genes for bipolar disorder. The first 97 pedigrees showed
      evidence of linkage to chromosomes 1, 6, 7, 10, 16, and 22 (Nurnberger et al
      1997). An additional 56 bipolar families have been genotyped, and the combined
      sample of 153 pedigrees studied. METHODS: Three hierarchical affection status
      models were analyzed with 513 simple sequence repeat markers; 298 were common
      across all pedigrees. The primary analysis was a nonparametric genome-wide scan.
      We performed conditional analyses based on epistasis or heterogeneity for five
      regions. RESULTS: One region, on 16p13, was significant at the genome-wide p <.05
      level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12) showed
      nominally significant linkage findings (p </=.01). Conditional analysis assuming
      epistasis identified a significant increase in linkage at four regions. Families
      linked to 6q24 showed a significant increase in nonparametric logarithms of the
      odds (NPL) scores at 5q11 and 7q21. Epistasis also was observed between 20p12 and
      13q21, and 16p13 and 9q21. CONCLUSIONS: The findings are presented in rank order
      of nominal significance. Several of these regions have been previously implicated
      in independent studies of either bipolar disorder or schizophrenia. The strongest
      finding is at 16p13 at D16S748 with an NPL of 3.3, there is evidence of epistasis
      between this locus and 9q21. Application of conditional analyses is potentially
      useful in larger sample collections to identify susceptibility genes of modest
      influence that may not be identified in a genome-wide scan aimed to identify
      single gene effects.

PMID- 14643095
TI  - State and trait influences on mood regulation in bipolar disorder: blood flow
      differences with an acute mood challenge.
AB  - BACKGROUND: Even in remission, patients with bipolar disorder (BD) remain
      sensitive to external stressors that can trigger new episodes. Imitating such
      stressors by the controlled transient exposure to an emotional stimulus may help
      to identify brain regions modulating this sensitivity. METHODS: Transient sadness
      was induced in 9 euthymic and in 11 depressed subjects with BD. Regional blood
      flow (rCBF) changes were measured using (15)O-water positron emission tomography.
      RESULTS: Common changes in both groups were increased rCBF in anterior insula and
      cerebellum and decreased rCBF in dorsal-ventral-medial frontal cortex, posterior
      cingulate, inferior parietal, and temporal cortices. Decreases in dorsal ventral
      medial frontal cortices occurred in both groups, but subjects in remission showed
      a greater magnitude of change. Unique to remitted subjects with BD were rCBF
      increases in dorsal anterior cingulate and in premotor cortex. Lateral prefrontal
      rCBF decreases were unique to depressed subjects with BD. At baseline, remitted
      subjects showed a unique increase in dorsal anterior cingulate and orbitofrontal
      cortex. CONCLUSIONS: Common rCBF changes in remitted and depressed subjects
      identifies potential sites of disease vulnerability. Unique cingulate and
      orbitofrontal changes both at baseline and with induced sadness seen in the
      absence of prefrontal rCBF decreases may identify regional interactions important
      to the euthymic state in this population.

PMID- 14643096
TI  - Amygdala hyperreactivity in borderline personality disorder: implications for
      emotional dysregulation.
AB  - BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are
      fundamental aspects of borderline personality disorder (BPD). The amygdala plays
      important roles in modulating vigilance and generating negative emotional states
      and is often abnormally reactive in disorders of mood and emotion. The aim of
      this study was to assess amygdala reactivity in BPD patients relative to normal
      control subjects. We hypothesized that amygdala hyperreactivity contributes to
      hypervigilance, emotional dysregulation, and disturbed interpersonal relations in
      BPD. METHODS: Using functional magnetic resonance imaging, we examined neural
      responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression
      (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV
      diagnosed BPD patients and the normal control subjects were assessed by a
      clinical research team in a medical school psychiatry department. RESULTS:
      Borderline patients showed significantly greater left amygdala activation to the
      facial expressions of emotion (vs. a fixation point) compared with normal control
      subjects. Post-scan debriefing revealed that some borderline patients had
      difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS:
      Pictures of human emotional expressions elicit robust differences in amygdala
      activation levels in borderline patients, compared with normal control subjects,
      and can be used as probes to study the neuropathophysiologic basis of borderline
      personality disorder.

PMID- 14643097
TI  - Magnetic resonance imaging study of corpus callosum abnormalities in patients
      with bipolar disorder.
AB  - BACKGROUND: This study was conducted to further examine the hypothesis of
      abnormalities in size of corpus callosum in subjects with bipolar disorder.
      METHODS: Sixteen right-handed DSM-IV bipolar I patients and 27 right-handed
      healthy control subjects were studied. A 1.5-T GE Signa magnet was used, and
      three-dimensional gradient echo imaging (spoiled gradient recall acquisition) was
      conducted. Area measurements of corpus callosum were obtained blindly, with a
      semi-automated software, by a well-trained rater. RESULTS: Right-handed bipolar I
      patients had significantly smaller total corpus callosum, genu, posterior body,
      and isthmus areas compared with right-handed healthy control subjects (analysis
      of covariance with age, gender, and intracranial volume as covariates, p <.05).
      Partial correlation analyses, controlled for intracranial volumes, found a
      significant inverse relationship between age and total callosal, genu, anterior
      body, isthmus, and circularity in healthy control subjects (p <.05) but not in
      bipolar patients (p >.05). CONCLUSIONS: Smaller callosal areas may lead to
      altered inter-hemispheric communication and be involved in the pathophysiology
      and cognitive impairment found in bipolar disorder.

PMID- 14643098
TI  - Association study of the human FZD3 locus with schizophrenia.
AB  - The FZD3 protein is a transmembrane receptor for secreted Wnt glycoproteins
      involved in the Wnt signal transduction cascades. The alteration of Wnt signal
      transduction cascades has been thought to be involved in producing the
      cytoarchitectural defects observed in schizophrenia. Because the human FZD3 gene
      is mapped to chromosome 8p21, which is a potential region containing a gene for
      schizophrenia, it may play a role in conferring susceptibility to the disease.
      This study was conducted with the detection of three single nucleotide
      polymorphisms (SNPs) located within the FZD3 locus by using the polymerase chain
      reaction-based restriction fragment length polymorphism (RFLP) analysis among 246
      schizophrenic family trios of Chinese Han descent.The transmission disequilibrium
      test (TDT) demonstrated that the three SNPs all showed a preferential
      transmission with a p value ranging from.0003-.000007. The global chi-squared
      test for haplotype transmission also showed a strong association (chi(2) = 48.84,
      df = 7, p <.000001).The strong association between the FZD3 locus and
      schizophrenia suggests that the gene itself may play a role in underlying
      schizophrenia, although a nearby gene responsible for predisposing to the illness
      cannot be ruled out.

PMID- 14643099
TI  - The amygdala and schizophrenia: a volumetric magnetic resonance imaging study in
      first-episode, neuroleptic-naive patients.
AB  - BACKGROUND: The attempts to evaluate amygdaloid volumes using magnetic resonance
      imaging (MRI) in patients with schizophrenia have yielded highly divergent
      results. METHODS: Volumes of the amygdala were measured in 22 healthy
      participants and 18 neuroleptic-naive patients with first-episode schizophrenia,
      while controlling for intracranial area, gender, age, and handedness. RESULTS:
      Persons with schizophrenia presented significantly lower amygdaloid volumes
      bilaterally. No significant correlations were found between the amygdaloid
      volumes and either the duration of the disease or the symptom severity.
      CONCLUSIONS: Amygdaloid volume anomalies are already present in the early phases
      of schizophrenia.

PMID- 14643101
TI  - Application of reproductive biotechnology in animals: implications and
      potentials. Applications of reproductive cloning.
AB  - The development of new methods of nuclear transfer in mammals is creating many
      new opportunities in research, medicine and agriculture. The method of cloning is
      repeatable and has been established in many laboratories worldwide. However, the
      present procedure is inefficient with fewer than 4% of embryos becoming viable
      offspring. A considerable improvement in efficiency is required before wide scale
      use for livestock improvement. The opportunity to introduce precise genetic
      changes to livestock is available for the first time through the use of gene
      targeting procedures in cultured cells that are used as nuclear donors. This has
      potential application in the production of organs for transplantation to humans,
      studies of human genetic disease and basic research in to the control of gene
      expression and function.

PMID- 14643102
TI  - Sexing mammalian sperm--intertwining of commerce, technology, and biology.
AB  - Sperm from many mammalian species can be sexed by flow cytometry/cell sorting at
      about 90% accuracy without damaging them unduly. However, because sperm are
      evaluated one at a time, in series, the number of sexed sperm produced per unit
      time is limited. Furthermore, the equipment required currently is expensive, in
      the order of 300,000 US dollars per machine. Despite these limitations,
      commercialization of this technology has begun with bovine semen, in part by
      inseminating cattle with relatively low number of sperms. No other approach to
      sexing sperm in any practical way is likely to be available within the next few
      years. The constraints for commercial application of sexed sperm in cattle can be
      somewhat lowered fertility, the high costs of equipment and skilled personnel,
      and costs of intellectual property such as licensing fees and royalty payments.
      Most economic analyses indicate that farmers can afford to pay 10-20 US dollars
      more per dose of sexed sperm than unsexed sperm if costs must be recouped by
      selling milk or meat. When the product is breeding stock or for certain niche
      applications, a higher price for sexed semen may be justified. Sexed sperm will
      be used more broadly in cattle only when improved production and/or efficiency
      can compensate for the extra costs of purchasing sexed sperm.

PMID- 14643103
TI  - Advances in deep uterine insemination: a fruitful way forward to exploit new
      sperm technologies in cattle.
AB  - After clarifying regions of the female tract wherein spermatozoa are stored and
      the egg is fertilised, proposals are made for a modified site of sperm deposition
      in cattle. A deep pre-ovulatory insemination into the ipsilateral horn of the
      uterus-the side of the ovulatory follicle-should improve establishment of viable
      spermatozoa in the caudal region of the oviduct isthmus, the so-called functional
      sperm reservoir. Suppressed motility within viscous secretions and binding of
      sperm heads to endosalpingeal microvilli are features of this phase of storage.
      Activation and release of such spermatozoa would be prompted by imminent
      ovulation and associated ovarian endocrine programming by both local and systemic
      routes. Potential advantages of deep insemination include: (1) raising the
      fertility of genetically valuable bulls whose non-return rates are sub-optimal;
      (2) reducing the number of spermatozoa in each insemination dose; (3) exploiting
      the limited numbers of sex-selected sperm cells (X- and Y-chromosome-bearing
      spermatozoa) available from flow cytometry; (4) breeding from valuable but
      oligospermic bulls. Putative disadvantages might include: (1) rectal palpation of
      the ovaries to identify the pre-ovulatory follicle; (2) damage to or even
      perforation of the uterine wall by the insemination device; (3) the risk of
      polyspermic fertilisation; (4) specific training in the technique for non
      clinically qualified inseminators. Each of these reservations receives comment.
      In conclusion, a modified technique of insemination should be feasible under
      commercial conditions, could be coupled with new sperm technologies, and would
      give a boost to the artificial insemination industry.

PMID- 14643105
TI  - The potential for improving the growth and development of cultured farm animal
      oocytes.
AB  - Previous predictions that the technologies for producing genetically engineered
      large animal embryos containing genes for faster growth rates, leaner carcasses,
      greater disease resistance and improved lactational performance would be
      available early in the twenty-first century have been, for the most part,
      realized. The animal industries have been slow to adopt these technological
      advances and it cannot be said that any of them are currently having great impact
      on animal agriculture worldwide. A major reason for this is the inefficiencies of
      the techniques for superovulation, ovum recovery, in vitro fertilization, nuclear
      transfer, cloning and embryo transfer. Although improvements in these techniques
      can be expected, the best hope for increasing the impact of embryo transfer
      technologies on the animal industries lies in developing ways to mature, harvest,
      store and fertilize in vitro the large numbers of primordial oocytes present in
      the ovaries of all farm animals. Although limited progress has been made in the
      culture of bovine primordial oocytes, it is clear that much more research is
      needed to achieve success in this important area.

PMID- 14643104
TI  - A review of in vitro gamete maturation and embryo culture and potential impact on
      future animal biotechnology.
AB  - This review considers the relationship of in vitro gamete maturation and embryo
      culture to the future development of animal biotechnology. The areas reviewed are
      oocyte maturation in vitro and embryo culture and their importance for successful
      in vitro embryo production. The rapidly developing area of spermatogonial cell
      transplantation and culture is also reviewed. The scientific milestones leading
      to the development of each area, the problems and prospects for future
      development and the possible significance of major advances in each area are
      discussed.

PMID- 14643106
TI  - A history of farm animal embryo transfer and some associated techniques.
AB  - Events over the last 125 years that have been particularly important to the
      development of embryo transfer in farm animals are reviewed, arguing that an
      appreciation of the history of a discipline helps shape its future. Special
      attention is paid to how the motivations of the scientists involved have changed
      over time, and how these changes have influenced the practical application of
      embryo transfer to animal breeding.

PMID- 14643107
TI  - The current status and future of commercial embryo transfer in cattle.
AB  - A commercially viable cattle embryo transfer (ET) industry was established in
      North America during the early 1970s, approximately 80 years after the first
      successful embryo transfer was reported in a mammal. Initially, techniques for
      recovering and transferring cattle embryos were exclusively surgical. However, by
      the late 1970s, most embryos were recovered and transferred nonsurgically.
      Successful cryopreservation of embryos was widespread by the early 1980s,
      followed by the introduction of embryo splitting, in vitro procedures, direct
      transfer of frozen embryos and sexing of embryos. The wide spread adoption of
      ethylene glycol as a cryoprotectant has simplified the thaw-transfer procedures
      for frozen embryos. The number of embryos recovered annually has not grown
      appreciably over the last 10 years in North America and Europe; however, there
      has been significant growth of commercial ET in South America. Within North
      America, ET activity has been relatively constant in Holstein cattle, whereas
      there has been a large ET increase in the Angus breed and a concomitant ET
      decrease in some other beef breeds. Although a number of new technologies have
      been adopted within the ET industry in the last decade, the basic procedure of
      superovulation of donor cattle has undergone little improvement over the last 20
      years. The export-import of frozen cattle embryos has become a well-established
      industry, governed by specific health regulations. The international movement of
      embryos is subject to sudden and dramatic disturbances, as exemplified by the
      2001 outbreak of foot and mouth disease in Great Britain. It is probable that
      there will be an increased influence of animal rights issues on the ET industry
      in the future. Several companies in North America are currently commercially
      producing cloned cattle. The sexing of bovine semen with the use of flow
      cytometry is extremely accurate and moderate pregnancy rates in heifers have been
      achieved in field trials, but sexed semen currently is available in only a few
      countries and on an extremely limited basis. As of yet, all programs involving
      the production of transgenic cattle are experimental in nature.

PMID- 14643108
TI  - Transgenic animals in biomedicine and agriculture: outlook for the future.
AB  - Transgenic animals are produced by introduction of 'foreign' deoxyribonucleic
      acid (DNA) into preimplantation embryos. The foreign DNA is inserted into the
      genetic material and may be expressed in tissues of the resulting individual.
      This technique is of great importance to many aspects of biomedical science
      including gene regulation, the immune system, cancer research, developmental
      biology, biomedicine, manufacturing and agriculture. The production of transgenic
      animals is one of a number of new and developing technologies that will have a
      profound impact on the genetic improvement of livestock. The rate at which these
      technologies are incorporated into production schemes will determine the speed at
      which we will be able to achieve our goal of more efficiently producing
      livestock, which meets consumer and market demand.

PMID- 14643109
TI  - Application of transgenesis in livestock for agriculture and biomedicine.
AB  - Microinjection of foreign DNA into pronuclei of a fertilized oocyte has
      predominantly been used for the generation of transgenic livestock. This
      technology works reliably, but is inefficient and results in random integration
      and variable expression patterns in the transgenic offspring. Nevertheless,
      remarkable achievements have been made with this technology. By targeting
      expression to the mammary gland, numerous heterologous recombinant human proteins
      have been produced in large amounts which could be purified from milk of
      transgenic goats, sheep, cattle and rabbit. Products such as human anti-thrombin
      III, alpha-anti-trypsin and tissue plasminogen activator are currently in
      advanced clinical trials and are expected to be on the market within the next few
      years. Transgenic pigs that express human complement regulating proteins have
      been tested in their ability to serve as donors in human organ transplantation
      (i.e. xenotransplantation). In vitro and in vivo data convincingly show that the
      hyperacute rejection response can be overcome in a clinically acceptable manner
      by successful employing this strategy. It is anticipated that transgenic pigs
      will be available as donors for functional xenografts within a few years.
      Similarly, pigs may serve as donors for a variety of xenogenic cells and tissues.
      The recent developments in nuclear transfer and its merger with the growing
      genomic data allow a targeted and regulatable transgenic production. Systems for
      efficient homologous recombination in somatic cells are being developed and the
      adaptation of sophisticated molecular tools, already explored in mice, for
      transgenic livestock production is underway. The availability of these
      technologies are essential to maintain "genetic security" and to ensure absence
      of unwanted side effects.

PMID- 14643110
TI  - Positive, accurate animal identification.
AB  - Positive, accurate identification of animals and their products would be very
      helpful in livestock commerce, prevention of theft and fraud and in tracing
      animals and products to origin. Food safety, animal health, and prevention of
      epidemics, would be enhanced by combining identification with location.
      Identification may be by electronic chips, iris or retinal scans, antibody or DNA
      analysis. A cross listing of one or more means in a central repository would
      facilitate tracing origin of animals and build confidence in transactions of all
      kinds.

PMID- 14643111
TI  - In war games, who wins?

PMID- 14643112
TI  - Can we pull the plug on warfarin in atrial fibrillation?

PMID- 14643113
TI  - A tale of two viruses: hepatitis C in the age of HAART.

PMID- 14643114
TI  - European Council waters down European Parliament's drug-regulatory legislation.

PMID- 14643115
TI  - Dementia with Lewy bodies.

PMID- 14643116
TI  - Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared
      with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III):
      randomised controlled trial.
AB  - BACKGROUND: Warfarin prevents ischaemic stroke in patients with non-valvular
      atrial fibrillation, but dose adjustment, coagulation monitoring, and bleeding
      risk limit its use. The oral direct thrombin inhibitor ximelagatran represents a
      potential alternative. We aimed to establish whether ximelagatran is non-inferior
      to warfarin, within a margin of 2% per year, for prevention of stroke and
      systemic embolism. METHODS: We randomised 3410 patients with atrial fibrillation
      and one or more stroke risk factors to open-label warfarin (adjusted-dose,
      international normalised ratio [INR] 2.0-3.0) or ximelagatran (fixed-dose, 36 mg
      twice daily); patients were recruited from 259 hospitals, doctor's offices, or
      health-care clinics. Primary analysis was based on masked event assessment and
      was by intention to treat. Primary endpoint was stroke or systemic embolism.
      FINDINGS: During 4941 patient-years of exposure (mean 17.4 months, SD 4.1), 96
      patients had primary events (56 in the warfarin group vs 40 in the ximelagatran
      group). The primary event rate by intention to treat was 2.3% per year with
      warfarin and 1.6% per year with ximelagatran (absolute risk reduction 0.7% [95%
      CI -0.1 to 1.4], p=0.10; relative risk reduction 29% [95% CI -6.5 to 52]). Rates
      of disabling or fatal stroke, mortality, and major bleeding were similar between
      groups, but combined minor and major haemorrhages were lower with ximelagatran
      than with warfarin (29.8% vs 25.8% per year; relative risk reduction 14% [4 to
      22]; p=0.007). Raised serum alanine aminotransferase was more common with
      ximelagatran. INTERPRETATION: In high-risk patients with atrial fibrillation,
      fixed-dose oral ximelagatran was at least as effective as well-controlled
      warfarin for prevention of stroke and systemic embolism.

PMID- 14643117
TI  - Cortical abnormalities in children and adolescents with attention-deficit
      hyperactivity disorder.
AB  - BACKGROUND: Results of structural brain imaging studies of patients with
      attention-deficit hyperactivity disorder have shown subtle reductions in total
      brain volume and in volumes of the right frontal lobe and caudate nucleus.
      Although various conventional volumetric and voxel-based methods of image
      analysis have been used in these studies, regional brain size and grey-matter
      abnormalities have not yet been mapped over the entire cortical surface in
      patients with this disorder. We aimed to map these features in patients with
      attention-deficit hyperactivity disorder. METHODS: We used high-resolution MRI
      and surface-based, computational image analytic techniques to map regional brain
      size and grey-matter abnormalities at the cortical surface in a group of 27
      children and adolescents with attention-deficit hyperactivity disorder and 46
      controls, who were group-matched by age and sex. FINDINGS: Abnormal morphology
      was noted in the frontal cortices of patients with attention-deficit
      hyperactivity disorder, with reduced regional brain size localised mainly to
      inferior portions of dorsal prefrontal cortices bilaterally. Brain size was also
      reduced in anterior temporal cortices bilaterally. Prominent increases in grey
      matter were recorded in large portions of the posterior temporal and inferior
      parietal cortices bilaterally. INTERPRETATION: The frontal, temporal, and
      parietal regions are heteromodal association cortices that constitute a
      distributed neural system, which subserves attention and behavioural inhibition.
      We have identified region-specific anatomical abnormalities in cortical
      components of attentional systems, which may help better account for the symptoms
      of attention-deficit hyperactivity disorder.

PMID- 14643118
TI  - Calciphylaxis.

PMID- 14643119
TI  - Effect of antiretroviral therapy on liver-related mortality in patients with HIV
      and hepatitis C virus coinfection.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the
      prognosis of HIV infection. However, replication of hepatitis C virus (HCV) is
      not inhibited by HAART, and treatment-related hepatotoxicity is common. To
      clarify the effect of HAART in HIV/HCV-coinfected patients, we studied liver
      related mortality and overall mortality in 285 patients who were regularly
      treated during the period 1990-2002 at our department. METHODS: Survival was
      analysed retrospectively by Kaplan-Meier and Cox's regression analyses after
      patients (81% haemophiliacs) had been stratified into three groups according to
      their antiretroviral therapy (HAART n=93, available after 1995; treatment
      exclusively with nucleoside analogues n=55, available after 1992; or no
      treatment, n=137). FINDINGS: Liver-related mortality rates were 0.45, 0.69, and
      1.70 per 100 person-years in the HAART, antiretroviral-treatment, and untreated
      groups. Kaplan-Meier analysis of liver-related mortality confirmed the
      significant survival benefit in patients with antiretroviral therapy (p=0.018),
      and regression analysis identified HAART (odds ratio 0.106 [95% CI 0.020-0.564]),
      antiretroviral treatment (0.283 [0.103-0.780]), CD4-positive T-cell count (0.746
      [0.641-0.868] per 0.05x10(9) cells/L), serum cholinesterase (0.962 [0.938-0.986]
      per 100 U/L), and age (1.065 [1.027-1.105] per year) as independent predictors of
      liver-related survival. Severe drug-related hepatotoxicity was seen in five
      patients treated with nucleoside analogues alone and 13 treated with HAART. No
      patient died from drug-related hepatotoxicity. INTERPRETATION: In addition to
      improved overall survival, antiretroviral therapy significantly reduced long-term
      liver-related mortality in our patients. This survival benefit seems to outweigh
      by far the associated risks of severe hepatotoxicity.

PMID- 14643120
TI  - Azoospermia in patients heterozygous for a mutation in SYCP3.
AB  - BACKGROUND: Many cases of male infertility are diagnosed as idiopathic,
      reflecting poor understanding of the molecular defects underlying the
      abnormality. As more gene mutations causing male infertility in mice become
      known, there are improving prospects that knowledge about the genetic aetiology
      of human male infertility can be expanded. Sycp3 encodes a component of the
      synaptonemal complex. A null mutation of Sycp3 in mice causes azoospermia with
      meiotic arrest. We tested the hypothesis that mutation of the human testis
      specific SYCP3 is associated with human non-obstructive azoospermia. METHODS:
      Human SYCP3 was isolated on the basis of homology between mouse Sycp3 cDNA and
      human genome sequences at the aminoacid level. Tissue-specific expression of
      SYCP3 was analysed by PCR of human cDNA. Samples of DNA from 19 azoospermic
      patients with maturation arrest and 75 normal fertile control men were screened
      for mutations in the SYCP3 gene by sequence analysis of the gene. The functional
      significance of the mutations found was analysed by a protein interaction study
      of the wild-type and truncated SYCP3 proteins. FINDINGS: We identified in two
      patients a 1 bp deletion (643delA) that results in a premature stop codon and
      truncation of the C-terminal, coiled-coil-forming region of the SYCP3 protein.
      The mutant protein showed greatly reduced interaction with the wild-type protein
      in vitro and interfered with SYCP3 fibre formation in cultured cells.
      INTERPRETATION: We suggest that SYCP3 has an essential meiotic function in human
      spermatogenesis that is compromised by the mutant protein via dominant negative
      interference.

PMID- 14643121
TI  - Abdominal pain, hypertension, and thrombocytopenia.

PMID- 14643122
TI  - Mental health of detained asylum seekers.
AB  - Asylum seekers arriving in the USA are likely to be held in detention for months
      or years pending adjudication of their asylum claims. We interviewed 70 asylum
      seekers detained in New York, New Jersey, and Pennsylvania. We used self-report
      questionnaires to assess symptoms of anxiety, depression, and post-traumatic
      stress disorder. At baseline, 54 (77%) participants had clinically significant
      symptoms of anxiety, 60 (86%) of depression, and 35 (50%) of post-traumatic
      stress disorder; all symptoms were significantly correlated with length of
      detention (p=0.004, 0.017, and 0.019, respectively). At follow-up, participants
      who had been released had marked reductions in all psychological symptoms, but
      those still detained were more distressed than at baseline. Our findings suggest
      detention of asylum seekers exacerbates psychological symptoms.

PMID- 14643123
TI  - Association of intercellular adhesion molecule-1 gene with type 1 diabetes.
AB  - Intercellular adhesion molecule-1 (ICAM-1) functions via its ligands, the
      leucocyte integrins, in adhesion of immune cells to endothelial cells and in T
      cell activation. The third immunoglobulin-like extracellular domain binds
      integrin Mac-1 and contains a common non-conservative aminoacid polymorphism,
      G241R. Phenotypically, ICAM-1 has been associated with type 1 diabetes, a T-cell
      mediated autoimmune disease. We assessed two independent datasets, and noted that
      R241 was associated with lower risk of type 1 diabetes than is G241 (3695
      families, relative risk 0.91, p=0.03; 446 families, 0.60, p=0.006). Our data
      indicate an aetiological role for ICAM-1 in type 1 diabetes, which needs to be
      confirmed in future genetic and functional experiments.

PMID- 14643124
TI  - Influenza.
AB  - Although most influenza infections are self-limited, few other diseases exert
      such a huge toll of suffering and economic loss. Despite the importance of
      influenza, there had been, until recently, little advance in its control since
      amantadine was licensed almost 40 years ago. During the past decade, evidence has
      accrued on the protection afforded by inactivated vaccines and the safety and
      efficacy in children of live influenza-virus vaccines. There have been many new
      developments in vaccine technology. Moreover, work on viral neuraminidase has led
      to the licensing of potent selective antiviral drugs, and economic decision
      modelling provides further justification for annual vaccination and a framework
      for the use of neuraminidase inhibitors. Progress has also been made on
      developing near-patient testing for influenza that may assist individual
      diagnosis or the recognition of widespread virus circulation, and so optimise
      clinical management. Despite these advances, the occurrence of avian H5N1, H9N2,
      and H7N7 influenza in human beings and the rapid global spread of severe acute
      respiratory syndrome are reminders of our vulnerability to an emerging pandemic.
      The contrast between recent cases of H5N1 infection, associated with high
      mortality, and the typically mild, self-limiting nature of human infections with
      avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular
      correlates of pathogenicity and underlines the need for continuing international
      research into pandemic influenza. Improvements in animal and human surveillance,
      new approaches to vaccination, and increasing use of vaccines and antiviral drugs
      to combat annual influenza outbreaks are essential to reduce the global toll of
      pandemic and interpandemic influenza.

PMID- 14643125
TI  - Learning from experience?

PMID- 14643126
TI  - CD2-associated protein and glomerular disease.
AB  - CONTEXT: Proteinuria is a major cause of progression in renal disease. The
      glomerular ultrafiltration barrier, containing highly differentiated podocytes,
      normally restricts protein access to the urine. Patients with urinary protein in
      the nephrotic range (>3.5 g daily) often have effaced podocyte foot-processes.
      Slit diaphragms span the gaps between foot processes as a barrier to
      macromolecules. Nephrin and podocin are slit-diaphragm proteins identified in
      families with congenital nephrotic syndromes. CD2-associated protein (CD2AP) is
      an adapter protein originally identified as a novel ligand interacting with the T
      cell-adhesion protein CD2. CD2AP knockout (-/-) mice develop a congenital
      nephrotic syndrome with podocyte foot-process effacements and die at 6 weeks of
      age from renal failure. CD2AP localises to the slit diaphragm and links nephrin
      and podocin to phosphoinositide 3-OH kinase; this complex has cell-signalling
      properties. STARTING POINT: The CD2AP +/- heterozygous mice developed by Jeong
      Kim and colleagues (Science 2003; 300: 1298-300) are haploinsufficient and
      develop glomerular changes at 9 months of age with a histological pattern similar
      to that in human focal segmental glomerulosclerosis. These researchers found that
      2 of 30 African-American patients with idiopathic focal segmental
      glomerulosclerosis had a CD2AP mutation that ablated expression of one allele.
      WHERE NEXT? Further studies should address the normal distribution of the CD2AP
      heterozygous mutation in different ethnic populations, because the association
      with human idiopathic focal segmental glomerulosclerosis could be accidental.
      Decreased expression of CD2AP in podocytes of individuals with the CD2AP
      heterozygous mutation would help to understand how the haploinsufficiency
      translates into increased susceptibility to renal disease. Transfection of
      podocytes with mutated CD2AP or study of cultured podocytes from CD2AP +/- mice
      would provide further insight into whether the nephrin-podocin-CD2AP signal
      transduction pathway is altered and leads to increased apoptosis of podocytes.
      Assuming that a decrease in CD2AP attenuates clearance of glomerular immune
      complexes, patients with other types of idiopathic glomerulonephritis should also
      have a CD2AP mutation. However, first studies looking at the most common form of
      glomerulonephritis, IgA nephropathy, have failed to show decreased renal CD2AP
      expression.

PMID- 14643127
TI  - Preoperative assessment.
AB  - Although anaesthetic and surgical procedures should be individualised for every
      patient, in practice many preoperative protocols and routines are used generally.
      In this article, we aim to emphasise: why preoperative assessment is important;
      how it should be done, and by whom; what can be expected; and the importance of
      test selection based on patients' needs and on scientific evidence of
      effectiveness. We outline the roles of preoperative medical assessment in
      otherwise healthy patients. Clinical history, preoperative questionnaires,
      physical examination, routine tests, individual risk-assessment, and fasting
      policies are investigated by review of published work. Cost of routine
      preoperative assessment, the anaesthetist's legal responsibility, and
      patients'views in the preoperative process are also considered. A thorough
      clinical preoperative assessment of the patient is more important than routine
      preoperative tests, which should be requested only when justified by clinical
      indications. Moreover, this practice eliminates unnecessary cost without
      compromising the safety and quality of care. Education and training of medical
      doctors should be more scientifically guided, emphasising the relevance of
      effectiveness, and cost-effectiveness in clinical decision-making and
      complemented by audit.

PMID- 14643128
TI  - HIV-associated adipose redistribution syndrome as a selective autonomic
      neuropathy.
AB  - Abnormal body-fat distribution in HIV-1-associated adipose redistribution
      syndrome (HARS) remains unexplained at present. White adipose tissue is
      controlled by humoral factors and by neural regulation. Sympathetic innervation
      stimulates lipolysis, whereas parasympathetic innervation has an anabolic
      influence on white adipose tissue. Results of neuroanatomical studies showed a
      clear somatotopy with respect to autonomic control of white adipose tissue by
      both the sympathetic and parasympathetic branch, with separate sets of autonomic
      neurons innervating either the subcutaneous or the visceral fat compartment.
      Thus, the CNS is likely to be a key player in regulation of body-fat
      distribution. We propose that HARS is mediated by effects of antiretroviral
      treatment on the CNS and could indicate a change in autonomic balance resulting
      in redistribution of adipose tissue.

PMID- 14643129
TI  - One standard, not two.

PMID- 14643130
TI  - One standard, not two.

PMID- 14643131
TI  - Making national DNA databases safer.

PMID- 14643132
TI  - Diagnostic criteria for polymyositis and dermatomyositis.

PMID- 14643134
TI  - Diabetes and the global burden of non-communicable disease.

PMID- 14643135
TI  - Argument for partial nicotine deregulation.

PMID- 14643136
TI  - Global burden of COPD in Japan and Asia.

PMID- 14643137
TI  - The greatest threat to women's health.

PMID- 14643138
TI  - High-titre measles vaccine and female mortality.

PMID- 14643139
TI  - Biomedical publications in an unstable region: the Arab world, 1988-2002.

PMID- 14643140
TI  - Human thermostat.

PMID- 14643141
TI  - Influenza vaccination coverage in Japan.

PMID- 14643142
TI  - Prevention campaigns for cardiovascular disease.

PMID- 14643144
TI  - E-mail and patients: a medicolegal minefield.

PMID- 14643145
TI  - A pointed observation.

PMID- 14643146
TI  - Assessment in medical training.

PMID- 14643149
TI  - Poison jars.

PMID- 14643151
TI  - Hunting for the real cancer genes.

PMID- 14643152
TI  - Drug designers learn their ABC.

PMID- 14643153
TI  - Harnessing chromium in the fight against diabetes.

PMID- 14643156
TI  - Investment decisions in pharmaceutical R&D projects.

PMID- 14643157
TI  - Vaccine discovery research by reverse engineering.

PMID- 14643158
TI  - Biotechnology discovery productivity: a note of caution.

PMID- 14643159
TI  - Controlled release technologies for drug delivery.

PMID- 14643161
TI  - Angiogenesis and bone repair.
AB  - The intimate connection, both physical and biochemical, between blood vessels and
      bone cells has long been recognized. Genetic, biochemical, and pharmacological
      studies have identified and characterized factors involved in the conversation
      between endothelial cells (EC) and osteoblasts (OB) during both bone formation
      and repair. The long-awaited FDA approval of two growth factors, BMP-2 and OP-1,
      with angiogenic and osteogenic activity confirms the importance of these two
      processes in human skeletal healing. In this review, the role of osteogenic
      factors in the adaptive response and interactive function of OB and EC during the
      multi-step process of bone repair will be discussed.

PMID- 14643162
TI  - Pharmacokinetic and pharmacodynamic considerations in gene therapy.
AB  - During gene therapy the concentration of plasmid DNA or oligonucleotides in the
      plasma can be quite different from their concentrations in the nucleus or cytosol
      where they exert their actions. For a better understanding of the apparent
      discrepancies between pharmacokinetics (PK) and pharmacodynamics (PD), a new
      concept for intracellular PK with an emphasis on the final efficacy of gene
      transcription is needed. Here, the conventional PK and intracellular PK and PD of
      non-viral gene delivery systems are discussed, together with a new concept,
      referred to as controlled intracellular disposition, which integrates these
      factors to gain a better understanding of gene expression in the nucleus. The
      importance of optimizing the system from a transcriptional point of view in the
      nucleus is also discussed. These new concepts must be integrated to develop an
      optimized non-viral gene delivery system.

PMID- 14643163
TI  - In vitro trans-monolayer permeability calculations: often forgotten assumptions.
AB  - In designing effective therapeutic strategies, novel drugs must exhibit favorable
      pharmacokinetic properties. The physicochemical characteristics of a drug, such
      as pK(a), molecular weight, solubility and lipophilicity, will influence the way
      the drug partitions from the aqueous phase into membranes, and thus, will
      influence its ability to cross cellular barriers, such as the lining of the
      gastrointestinal tract and the blood-brain barrier. Physicochemical
      characteristics also influence the degree to which a drug is able to cross a
      barrier layer, and the route by which it does this; whether transcellular (across
      the cells)-by diffusion, carrier-mediated transport or transcytosis-or
      paracellular-by diffusing through the tight junctions between the cells. The in
      vitro model systems that are currently employed to screen the permeation
      characteristics of a drug often represent a compromise between high throughput
      with low predictive potential and low throughput with high predictive potential.
      Here, we will examine the way in which in vitro cellular permeability assays are
      often performed and the assumptions that are implied but sometimes forgotten, and
      we will make simple suggestions for improving the methodological techniques and
      mathematical equations used to determine drug permeability.

PMID- 14643164
TI  - Combinatorial chemistry.

PMID- 14643166
TI  - Effect of a novel NK1 receptor selective antagonist (NKP608) on citric acid
      induced cough and airway obstruction.
AB  - The effects of an orally administered novel and selective NK1 antagonist, NKP608,
      on cough and airway obstruction, induced by citric acid in guinea pigs, were
      investigated. Guinea pigs were pre-treated with 0.03, 0.3 and 1 mg kg(-1) of
      NKP608, the NK2 antagonist, SR48968 or both 2 h prior to challenge with citric
      acid (0.6 M) for a 10 min period. Guinea pigs pre-treated with 0.03, 0.3 and
      1mgkg(-1) of NKP608 exhibited a significant reduction of 77, 74 and 79%,
      respectively, in the numbers of cough compared to vehicle pre-treated animals
      (P<0.05). SR48968, 10 mg kg(-1), alone did not significantly affect the citric
      acid-induced cough but when co-administered with 1 mg kg(-1) of NKP608, there was
      a significant 90% reduction in cough. NKP608 did not significantly reduce the
      citric acid-induced increase in Penh at any of the doses used. SR48968
      significantly reduced the citric acid induced airway obstruction by about 50%.
      However, when SR48968 was co-administered with NKP608, there was a greater (73%)
      decrease in the airway obstruction compared with SR48968 alone. These data show
      that NKP608, a selective NK1 receptor antagonist, is a potent inhibitor of citric
      acid induced cough in guinea pigs and may therefore have value in the therapy of
      clinical cough.

PMID- 14643165
TI  - Development of cell adhesion molecule antagonists as therapeutics for asthma and
      COPD.
AB  - Airway inflammation is a hallmark of respiratory diseases such as asthma and
      chronic obstructive pulmonary disease. Cell adhesion molecules play critical
      roles in the recruitment and migration of cells to sites of inflammation. Not
      surprisingly, these receptors have garnered the attention of the pharmaceutical
      industry as targets for the development of drugs to treat inflammatory and
      autoimmune diseases. Although several potential cell adhesion targets exist,
      development of compounds for pulmonary indications has centered around the
      selectins and the integrin VLA-4. In vitro and in vivo studies have implicated
      these receptors in the recruitment of inflammatory cells to the lung as well as
      to key cellular activation pathways. Several first generation compounds are
      currently in clinical development for asthma. Positive data from a phase II
      clinical trial using an inhaled formulation of a selectin antagonist has recently
      been reported. Initial results from clinical trials using first generation VLA-4
      antagonists have been less promising but additional trials with more fully
      optimized compounds are underway. Results from these trials will provide insight
      into what the future holds for this exciting new class of drugs to treat
      pulmonary diseases.

PMID- 14643167
TI  - Serotonin uptake and metabolism by cultured guinea pig airway smooth muscle
      cells.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is synthesized and released in the airways
      by pulmonary neuroendocrine cells located in the vicinity of airway smooth muscle
      (ASM). The aim of this study was to determine whether ASM cells contribute to the
      inactivation of serotonin, and investigate the role of the serotonin transporter
      (SERT) and monoamine oxidase (MAO) in this process. Cultured guinea pig tracheal
      smooth muscle cells, maintained in culture medium containing serotonin for 1-4
      days, induced a decrease in 5-HT and increase in 5-HIAA in the culture medium.
      Changes in indole concentrations were prevented by fluvoxamine and iproniazid.
      Na+-sensitive [3H]-serotonin uptake into cultured ASM cells was time- and
      concentration-dependent (Km, 561 nM; Vmax, 1.06 pmol/mg protein/min), and
      inhibited by clomipramine (IC50, 13.7 nM), fluvoxamine (IC50, 0.16 microM) and
      fluoxetine (IC50, 0.32 microM). Western blot analysis with an anti-SERT antibody
      revealed a single 115 kDa immunoreactive band in ASM cell lysates. The results of
      this study suggest that ASM contributes to the uptake and metabolism of serotonin
      via SERT and MAO, respectively, and may therefore play a role in the inactivation
      of endogenous serotonin generated within the airway wall.

PMID- 14643168
TI  - Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in
      patients with COPD. Double-blind, randomized, multicenter, placebo-controlled
      study (the AMETHIST Trial).
AB  - The objective of this prospective, randomized, double-blind, placebo-controlled,
      multicenter parallel-group study was to evaluate the effect of long-term ambroxol
      treatment in preventing exacerbations of chronic obstructive pulmonary disease
      (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria
      with value of FEV1 between > or =60 and 80% of predicted and history of one or
      more exacerbations in the previous year were recruited by 26 Respiratory Medicine
      Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg
      twice daily or placebo. The percentage of patients free from exacerbation at 6
      months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56%
      with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with
      more severe baseline symptoms, ambroxol therapy was associated with a significant
      higher percentage of patients free from exacerbation compared to placebo: 63 vs.
      38% (p=0.038). In conclusion, we did not find a significant difference between
      long-term ambroxol therapy and placebo, in preventing exacerbations in patients
      with COPD. In patients with more severe respiratory symptoms at baseline,
      however, we observed a significant difference in the cumulative exacerbation-free
      persistence between ambroxol and placebo, suggesting that long-term muco
      regulatory therapy with ambroxol could be useful in highly symptomatic patients
      with COPD.

PMID- 14643169
TI  - The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and
      their combination in patients with COPD.
AB  - The aim of this double-blind, double-dummy, cross-over, randomized, pilot study
      was to compare the acute bronchodilator efficacy of a single dose of formoterol
      with that of tiotropium in patients with stable chronic obstructive pulmonary
      disease (COPD). Because the potential of tiotropium for additive effects is yet
      unknown, the acute effects of adding this anticholinergic agent to formoterol
      were also explored. A total of 20 outpatients with stable COPD were enrolled.
      Single doses of 12 microg formoterol, 18 microg tiotropium, and 12 microg
      formoterol+18 microg tiotropium were given. Serial measurements of FEV1 were
      performed over 24 h. Formoterol, either alone or in combination with tiotropium,
      elicited a significantly faster onset of action and showed a trend for a greater
      maximum bronchodilation than tiotropium alone. At 24 h, mean FEV1 continued to be
      significantly higher than pre-dosing value following tiotropium and
      formoterol+tiotropium. These findings indicate that formoterol and tiotropium
      have different profiles that make both agents attractive alternatives in the
      treatment of stable COPD. Since tiotropium ensures prolonged bronchodilation,
      whereas formoterol adds fast onset and a greater peak effect, the two drugs
      appear complementary.

PMID- 14643170
TI  - Inhibition of chemokine production from human airway smooth muscle cells by
      fluticasone, budesonide and beclomethasone.
AB  - Human airway smooth muscle cells (HASMC) contribute to the process of airway wall
      remodelling in asthma by virtue of their secretory functions. This study was
      performed to investigate the effectiveness of the commonly used steroids
      beclomethasone, budesonide and fluticasone in downregulating HASMC production of
      RANTES and IL-8. HASMC (n=5) were cultured from dissected bronchi using
      collagenase digestion. Confluent HASMC were exposed to TNFalpha and IL-1beta (10
      ng/ml) for 24 h. All stimulations were set with and without pre-treatment with
      beclomethasone, budesonide or fluticasone for 2 h at concentrations of 10(-9)-10(
      6)M. IL-8 and RANTES mRNA expression was assessed by RT-PCR and protein secretion
      was determined by ELISA. Pre-treatment with beclomethasone, budesonide or
      fluticasone reduced TNFalpha- and IL-1beta-stimulated IL-8 and RANTES release
      from HASMC in a dose dependent manner. However, beclomethasone was 22-28% less
      effective than fluticasone and budesonide in inhibiting chemokine production.
      TNFalpha- and IL-1beta-induced RANTES and IL-8 expression was reduced on the
      transcriptional level by pre-treatment with fluticasone and budesonide. The
      results suggest that the topical steroids fluticasone, budesonide and to a lesser
      extent beclomethasone may have beneficial effects on airway inflammation in
      asthma by reducing RANTES and IL-8-induced leukocyte infiltration into the airway
      wall.

PMID- 14643171
TI  - Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.
AB  - In this study, we determined the effect of inhaled nitric oxide (NO) on the acute
      lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung.
      Typical acute lung injury was induced successfully by PMA during 60 min of
      observation. PMA (2 microg/kg) elicited a significant increase in microvascular
      permeability, (measured using the capillary filtration coefficient Kfc), lung
      weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and
      protein concentration of the bronchoalveolar lavage fluid. Pretreatment with
      inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the
      parameters reflective of lung injury increased significantly except PAP (P<0.05).
      Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM)
      attenuated the detrimental effect of inhaled NO in PMA-induced lung injury,
      except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced
      acute lung injury except for PAP. These experimental data suggest that inhaled NO
      significantly exacerbated acute lung injury induced by PMA in rats. L-NAME
      attenuated the detrimental effect of inhaled NO.

PMID- 14643172
TI  - Inhaled milrinone for the improvement of contractility of fatigued diaphragm in
      dogs: a dose-ranging study.
AB  - The present study was undertaken to evaluate the efficacy of inhaled milrinone on
      contractility of fatigued diaphragm in dogs. Animals were divided into four
      groups of seven each. In each group, diaphragmatic fatigue was induced by
      intermittent supramaximal bilateral electrophrenic stimulation at a frequency of
      20 Hz applied for 30 min. Immediately after the end of a fatigue-producing
      period, Group I received inhaled vehicle; Group II received inhaled milrinone 0.1
      mg/ml (1 mg); Group III received inhaled milrinone 0.2 mg/ml (2 mg); Group IV
      received 0.5 mg/ml (5 mg). Study drug was administered for 30 min. Diaphragmatic
      contractility was assessed by transdiaphragmatic pressure (Pdi). After the
      fatigue-producing period, in each group, Pdi at low-frequency (20 Hz) decreased
      from baseline values (P<0.05), and Pdi at high-frequency (100 Hz) stimulation did
      not change. In Groups III and IV, during milrinone inhalation, Pdi at both
      stimuli increased from fatigued values (P<0.05). The increase in Pdi was more in
      Group IV than in Group III (P<0.05). Compared with Group I, Pdi to each stimulus
      did not change in Group II. In conclusion, inhaled milrinone, in doses more than
      0.2 mg/ml, is effective for improving contractility of fatigued diaphragm in
      dogs.

PMID- 14643173
TI  - Protective effect of D-003 on experimental spinal cord ischemia in rabbits.
AB  - D-003 is a natural mixture of long chain aliphatic acids isolated and purified
      from sugar cane wax. It possesses antiplatelet and antithrombotic effects as well
      as decreases plasma and serum levels of thromboxane B(2) (TxB(2)), meanwhile
      significantly and markedly raises prostacyclin (PgI(2)) levels in rats. This
      study was undertaken to investigate the effects of D-003 on spinal cord injury in
      rabbits. New Zealand rabbits were treated during 10 days with D-003 (25 and 200
      mg kg(-1)) and ASA (2 mg kg(-1)) before spinal cord ischemia. Animals were
      subjected to 20 min of aortic occlusion and 24h of reperfusion. Clinical symptoms
      and histopathological changes of spinal cord were observed. The PgI(2) levels in
      thoracic aorta were quantified by bioassay. D-003 (25 and 200 mg kg(-1))
      significantly increased the mean scores reached 4h after reperfusion, although no
      dose relation was observed. Twenty-four hours after reperfusion, no deaths
      occurred in both sham and D-003 treated groups, meanwhile in positive controls
      and ASA the mortality rate was 38.5% and 7.69% respectively. In addition, 100% of
      sham, 69% and 77% of rabbits treated with D-003 at 25 and 200 mg kg(-1),
      respectively, did not show histopathological changes. By the contrary, 100% of
      positive control animals showed severe damage and ASA-treated rabbits showed only
      a partial protection. Animals treated with both doses of D-003 showed PgI(2)
      levels significantly larger than those of positive and negative controls, an
      effect dose-related, while ASA 2 mg kg(-1) did not change PgI(2) values. The
      increase of PgI(2) levels achieved in the D-003 treated animals could be an
      important mechanism in the protection against the spinal cord ischemia.

PMID- 14643174
TI  - 15-Lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer.
AB  - The localization of 15-lipoxygenase-1 (15-LO-1) in human colorectal carcinoma and
      normal adjacent tissue was examined using immunohistochemistry. In normal
      tissues, 15-LO-1 was strongly localized in the mucosal epithelium. Conversely, in
      tumor tissues, staining for 15-LO-1 was dispersed throughout the tissue, weak in
      neoplastic epithelium, and strong in stromal inflammatory cells. The addition of
      50 microM 13(S)-hydroxyeicosatetraenoic acid (HODE), resulted in decreased cell
      proliferation after 72 h, but lower concentrations (5 or 10 microM) had no effect
      compared to vehicle treated Caco-2 cells. In addition, 13(S)-HODE had no effect
      on apoptosis or differentiation of the Caco-2 cells. Microarray analyses of RNA
      from Caco-2 cells treated with 5 microM 13(S)-HODE revealed changes in 17 genes.
      HCT-116 colorectal cells were stably transfected with 15-LO-1. In athymic nude
      mice, transplantable tumors derived from 15-LO-1 HCT-116 cells were smaller than
      tumors derived from vector HCT-116 cells. These data demonstrate that 13(S)-HODE
      induces changes in gene expression and has anti-tumorigenic effects.

PMID- 14643176
TI  - Occlusion of infusion vessels on gamma-linolenic acid infusion.
AB  - gamma-Linolenic acid (GLA) is known to have selective tumoricidal action. In this
      study, the effect of lithium salt of GLA conjugated to iodized lymphographic oil
      (LGIOC) was injected intra-arterially close to the origin of tumor-feeding
      vessel(s) was studied. Four patients with stage 4 cancer disease (2 with
      hepatocellular carcinoma, 1 with giant cell tumor of the bone, and one with renal
      cell carcinoma), were selected for the study. Angiography, radiography and
      computed axial tomography were performed prior to and immediately after the
      injection of LGIOC and at periodic intervals. All four patients tolerated the
      treatment well. The most significant observation was the complete occlusion of
      the tumor-feeding vessels after LGIOC injection. Follow-up angiograms performed
      in all the patients showed occlusion of the tumor-feeding vessels is more or less
      permanent. A significant reduction in the size of the tumor was also observed in
      these patients. LGIOC showed occlusion of tumor-feeding vessels after infusion,
      and further studies are needed to confirm these preliminary results.

PMID- 14643175
TI  - Influence of interleukin-1alpha and COX-2 over the metabolism of arachidonic acid
      and glucose in isolated uterus of restricted diet rats.
AB  - Isolated uteri from rats fed with a normal diet convert [14C]arachidonate into
      eicosanoids: PGE(2), PGF(2alpha), TXB(2) and 6-keto-F(1alpha). Restricted diet
      (50% of the normal diet, during 25 days) diminishes the levels of PGE(2),
      PGF(2alpha) and TXB(2). The addition of Interleukin-1alpha to the Krebs-Ringer
      bicarbonate medium increases sharply the production of eicosanoids. Inhibitors of
      nitric oxide synthase, Nomega-nitro-L-arginine methyl ester or aminoguanidine, do
      not prevent eicosanoids increase. Conversely, NS-398 (a selective inhibitor of
      COX-2) blocks the increase of eicosanoids while PGE(2) blocks eicosanoids
      production mediated by IL-1alpha. Other experiments with uteri of underfed rats
      confirm that interleukin-1alpha produces an increase in the glucose metabolism.
      The addition of Nomega-nitro-L-arginine methyl ester, aminoguadinine or NS-398
      blocked such stimulation. It is concluded that Interleukin-1alpha produces an
      increase of glucose metabolism in uteri isolated from underfed rats by two
      different mechanisms, both involving COX-2: (1) nitric oxide independent and (2)
      nitric oxide dependent.

PMID- 14643177
TI  - Epidermal growth factor modulation of prostaglandins and nitrite biosynthesis in
      rat fetal membranes.
AB  - The production of prostaglandins (PGs) and nitric oxide (NO) by amnion tissue may
      play a significant role in parturition. It is thought that epidermal growth
      factor (EGF) may be one of the fetal signals that governs the initiation of
      labor. The aim of the present study was to investigate the effect of EGF in vivo
      on the PGs and nitrite production of rat fetal membranes. We have evaluated the
      regulation of PGs and nitrite production in rat fetal membranes ex vivo. The
      intra-uterine administration of EGF 500 ng in day 21 of pregnancy induced
      increases in PGE(2) (P<0.001) and PGF(2alpha) (P<0.01) compared to the control
      fetal membranes from pregnant rats on day 22. Also, this dose of EGF diminished
      nitrate production significantly (P<0.01). We found that fetal membranes at term
      (days 18-22 of gestation) expressed EGF-R. The NO donor, nitroprussiate 300 and
      600 microM, elicited an inhibitory effect on the PGE(2) and PGF(2alpha)
      stimulated synthesis. On the other hand, indomethacin 10(-6) and 10(-7)M, a non
      selective cyclooxygenase inhibitor, reverted the inhibitory effect exerted by
      EGF. Hence, rat fetal membranes were found to express epidermal growth factor
      receptors and, under the effect of EGF, PGs and nitrites production pathways
      interact probably to prevent a toxic effect caused by an exacerbated synthesis of
      these mediators.

PMID- 14643178
TI  - Alpha-linolenic acid supplementation during human pregnancy does not effect
      cognitive functioning.
AB  - Increasing evidence suggests a positive association between docosahexaenoic acid
      (DHA, 22:6n-3) and cognitive performance. In addition, pregnancy is associated
      with a reduction of the DHA status and cognitive deficits. In the current study,
      cognition was assessed in pregnant women receiving a margarine enriched with
      alpha-linolenic acid (ALA, 18:3n-3, the ultimate dietary precursor of DHA) and
      some linoleic acid (LA, 18:2n-6, to prevent a possible reduction in n-6 fatty
      acids). A control group received a margarine enriched with LA only. ALA
      supplementation hardly affected the maternal DHA status and no significant
      differences were found in cognitive performance between the two groups. This
      indicates that ALA supplementation during pregnancy does not affect cognitive
      performance during and 32 weeks after gestation. At week 14 of pregnancy and 32
      weeks after delivery, higher plasma DHA levels were associated with lower
      cognitive performance as indicated by longer reaction times on the finger
      precuing task (partial correlation coefficients 0.3705 and 0.4633, respectively,
      P<0.01). Since this could imply an unexpected adverse association between DHA and
      certain aspects of cognitive functioning this certainly needs further
      investigation.

PMID- 14643179
TI  - Phosphatidyl choline fatty acid remodeling in the hepatic cell nuclei.
AB  - This study was performed to determine whether fatty acids incorporated into liver
      cell nuclei phosphatidylcholine (PtdCho) could be remodeled in the isolated
      nuclear. For this reason, rat liver cell nuclei were incubated in vitro with [1
      14C]20:4n-6-CoA. PtdCho molecular species with the highest specific activity had
      an unsaturated fatty acid at sn-1 and sn-2 positions (20:4-20:4>18:2-20:4>18:1
      20:4). 16:0-20:4 and 18:0-20:4 PtdChos showed a minor specific activity. When
      labeled nuclei were reincubated in the absence of labeled substrate with the
      addition of cytosol, ATP and CoA, the specific activity of 20:4-20:4, 18:2-20:4
      and 18:1-20:4 species decreased, while that of 16:0-20:4 and 18:0-20:4 increased.
      In conclusion, the asymmetric fatty acid distribution of saturated fatty acids at
      sn-1 position, and unsaturated fatty acids at sn-2 position of nuclear PtdCho
      molecular species was re-established by an acyl-CoA-dependent remodeling process.

PMID- 14643180
TI  - Exchange of unsaturated fatty acids between adipose tissue and atherosclerotic
      plaque studied with artificial neural networks.
AB  - The linoleic C18:2 (n-6) and linolenic C18:3 (n-3) are recognized as essential
      components of the diet. Free radical peroxidation of essential fatty acids (EFAs)
      present in lipoproteins produces oxidized low-density lipoproteins which play a
      critical role in the development of atherosclerosis. The accumulation of EFAs in
      the vascular wall and correlations between their content in the adipose tissue
      and atherosclerotic plaque have been confirmed. The present study was undertaken
      to determine the usefulness of a neural network for studying the exchange between
      tissues of linoleic, alpha-linolenic, and arachidonic acids-three fatty acids
      with a well-understood metabolism. Atheromatous plaques, adipose tissue, and
      serum were obtained from 31 patients who underwent surgery due to atherosclerotic
      stenosis of the abdominal aorta, iliac or femoral arteries. Fatty acids were
      extracted and separated as methyl esters using gas chromatography. Statistical
      analysis was done with STATISTICA neural networks package. Several correlations
      reported previously were corroborated and factors modifying the content of
      individual EFAs in adipose tissue and atherosclerotic plaque were revealed.
      Artificial neural networks (ANNs) were used to determine factors modifying the
      content of linoleic, alpha-linolenic, and arachidonic acids in human atheromatous
      plaques. The mechanism of exchange of some fatty acids between the adipose
      tissue, atheromatous plaque, and plasma is discussed. The results provide
      evidence for an effective mechanism of tissue uptake and turnover of linoleic
      acid. Reduced plasma levels of this acid are compensated by release from adipose
      tissue and atheromatous plaque. While alpha-linolenic acid is continuously taken
      up by the plaque, adipose tissue absorbs this acid to a certain level only. The
      dynamics of exchange of arachidonic acid between adipose tissue and atheromatous
      plaque reflects a minor role for adipose tissue in determining plaque content of
      this acid, suggesting that "de novo" synthesis is the chief source of arachidonic
      acid in plaques.

PMID- 14643181
TI  - Involvement of eicosanoids in the hypothermic response to lipopolysaccharide
      during endotoxemia in rats.
AB  - Hypothermia is one of the prominent features of the acute phase response to
      endotoxin (LPS). This study was undertaken to elucidate the effects of the COX
      inhibitor Indomethacin (INDO) and the selective FLAP inhibitor MK-886 on LPS
      induced hypothermia, mortality and increase in production of hypothalamic
      prostaglandin E(2) (PGE(2)) and leukotriene during endotoxemia. It has been
      demonstrated that INDO and MK-886 significantly attenuate the hypothermia induced
      by LPS, but MK-886 has a lesser (protective) effect than INDO. Only INDO was
      found to attenuate significantly the hyperthermic response to LPS. Furthermore,
      INDO significantly reduced the elevation in hypothalamic PGE(2) levels. MK-886
      significantly reduced the elevation in hypothalamic leukotriene production only
      when LPS was given in a dose of 1mg/kg. Both drugs failed to reduce the elevation
      in plasma TNF-alpha and mortality induced by LPS. We conclude that in rats,
      febrile response to endotoxin involves many inflammatory mediators. However, it
      seems that PGE(2) and leukotrienes do not have a pivotal role in the mechanism of
      LPS-induced mortality.

PMID- 14643183
TI  - Effects of dispersal mechanisms on spatio-temporal development of epidemics.
AB  - The nature of pathogen transport mechanisms strongly determines the spatial
      pattern of disease and, through this, the dynamics and persistence of epidemics
      in plant populations. Up to recently, the range of possible mechanisms or
      interactions assumed by epidemic models has been limited: either independent of
      the location of individuals (mean-field models) or restricted to local contacts
      (between nearest neighbours or decaying exponentially with distance). Real
      dispersal processes are likely to lie between these two extremes, and many are
      well described by long-tailed contact kernels such as power laws. We investigate
      the effect of different spatial dispersal mechanisms on the spatio-temporal
      spread of disease epidemics by simulating a stochastic Susceptible-infective
      model motivated by previous data analyses. Both long-term stationary behaviour
      (in the presence of a control or recovery process) and transient behaviour (which
      varies widely within and between epidemics) are examined. We demonstrate the
      relationship between epidemic size and disease pattern (characterized by spatial
      autocorrelation), and its dependence on dispersal and infectivity parameters.
      Special attention is given to boundary effects, which can decrease disease levels
      significantly relative to standard, periodic geometries in cases of long-distance
      dispersal. We propose and test a definition of transient duration which captures
      the dependence of transients on dispersal mechanisms. We outline an analytical
      approach that represents the behaviour of the spatially-explicit model, and use
      it to prove that the epidemic size is predicted exactly by the mean-field model
      (in the limit of an infinite system) when dispersal is sufficiently long ranged
      (i.e. when the power-law exponent a</=2).

PMID- 14643182
TI  - Acceleration of superoxide generation in polymorphonuclear leukocytes and
      inhibition of platelet aggregation by alk(en)yl thiosulfates derived from onion
      and garlic in dogs and humans.
AB  - We recently identified sodium n-propyl thiosulfate (NPTS) and sodium 2-propenyl
      thiosulfate (2PTS) from boiled onion and garlic, respectively, as causative
      agents of hemolytic anemia in dogs. We present here data concerning the effects
      of these alk(en)yl thiosulfates on superoxide (O(2)(-)) generation in peripheral
      polymorphonuclear leukocytes (PMNs) and on adenosine 5'-diphosphate (ADP)-induced
      platelet aggregation in dogs and humans in vitro. Both NPTS and 2PTS increased
      O(2)(-) generation significantly (P<0.05 at 1mM NPTS, P<0.005 at 0.1 and 1mM
      2PTS) and reduced its reaction time significantly (P<0.05 between 0.01 and 1mM
      NPTS and at 1mM 2PTS) in canine PMNs stimulated by phorbol 12-myristate 13
      acetate, compared with the control without alk(en)yl thiosulfates. However, a
      tendency to return to the control level was observed at 10mM of the alk(en)yl
      thiosulfates in both O(2)(-) generation and its reaction time. Although NPTS and
      2PTS did not exert any significant effect on the O(2)(-) generation in human
      PMNs, 2PTS reduced its reaction time significantly (P<0.05) at 1 and 10mM
      compared with the control, showing that 2PTS accelerated O(2)(-) generation in
      human PMNs. The difference in effects on O(2)(-) generation may be due to that in
      susceptibility to alk(en)yl thiosulfates between canine and human PMNs. On the
      other hand, NPTS and 2PTS were shown to significantly inhibit ADP-induced
      platelet aggregation at 0.01mM (P<0.01) in canine platelets and at 0.001-0.1mM
      (P<0.05) in human platelets. In contrast, the maximal aggregation percentage
      returned to the control level at 1mM of alk(en)yl thiosulfates in both canine and
      human platelets. From these results, we conclude that NPTS and 2PTS have the
      potential to promote immune functions and prevent cardiovascular diseases.

PMID- 14643184
TI  - Growth of mixed cultures on mixtures of substitutable substrates: the operating
      diagram for a structured model.
AB  - The growth of mixed microbial cultures on mixtures of substrates is a problem of
      fundamental biological interest. In the last two decades, several unstructured
      models of mixed-substrate growth have been studied. It is well known, however,
      that the growth patterns in mixed-substrate environments are dictated by the
      enzymes that catalyse the transport of substrates into the cell. We have shown
      previously that a model taking due account of transport enzymes captures and
      explains all the observed patterns of growth of a single species on two
      substitutable substrates (J. Theor. Biol. 190 (1998) 241). Here, we extend the
      model to study the steady states of growth of two species on two substitutable
      substrates. The model is analysed to determine the conditions for existence and
      stability of the various steady states. Simulations are performed to determine
      the flow rates and feed concentrations at which both species coexist. We show
      that if the interaction between the two species is purely competitive, then at
      any given flow rate, coexistence is possible only if the ratio of the two feed
      concentrations lies within a certain interval; excessive supply of either one of
      the two substrates leads to annihilation of one of the species. This result
      simplifies the construction of the operating diagram for purely competing
      species. This is because the two-dimensional surface that bounds the flow rates
      and feed concentrations at which both species coexist has a particularly simple
      geometry: It is completely determined by only two coordinates, the flow rate and
      the ratio of the two feed concentrations. We also study commensalistic
      interactions between the two species by assuming that one of the species excretes
      a product that can support the growth of the other species. We show that such
      interactions enhance the coexistence region.

PMID- 14643185
TI  - The role of density-dependent dispersal in source-sink dynamics.
AB  - I investigate two aspects of source-sink theory that have hitherto received
      little attention: density-dependent dispersal and the cost of dispersal to
      sources. The cost arises because emigration reduces the per capita growth rate of
      sources, thus predisposing them to extinction. I show that source-sink
      persistence depends critically on the interplay between these two factors. When
      the emigration rate increases with abundance at an accelerating rate, dispersal
      costs to sources is the lowest and risk of source-sink extinction the least. When
      the emigration rate increases with abundance at a decelerating rate, dispersal
      costs to sources is the highest and the risk of source-sink extinction the
      greatest. Density-independent emigration has an intermediate effect. Thus,
      density-dependent dispersal per se does not increase or decrease source-sink
      persistence relative to density-independent dispersal. The exact mode of
      dispersal is crucial. A key point to appreciate is that these effects of
      dispersal on source-sink extinction arise from the temporal density-dependence
      that dispersal induces in the per capita growth rates of source and sink
      populations. Temporal density-dependence due to dispersal is beneficial at low
      abundances because it rescues sinks from extinction, and detrimental at high
      abundances because it drives otherwise viable sources to extinction. These
      results are robust to the nature of population dynamics in the sink, whether
      exponential or logistic. They provide a means of assessing the relative costs and
      benefits of preserving sink habitats given three biological parameters.

PMID- 14643186
TI  - A kinetic model of telomere shortening in infants and adults.
AB  - We have previously demonstrated that telomeres shorten more rapidly in peripheral
      mononuclear cells (PBMC) of infants than in adults (Zeichner et al., Blood 93
      (1999) 2824). Here we describe a mathematical model that allows quantification of
      telomere dynamics both in infants and in adults. In this model the dependence of
      the telomere dynamics on age is accounted by assuming proportionality between the
      body growth, as approximated by the Gompertz equation, and the increase in the
      number of PBMCs. The model also assumes the existence of two subpopulations of
      PBMC with significantly different rates of division. This assumption is based on
      the results from a previous analysis of in vitro data for telomere dynamics in
      presence of telomerase inhibitors and our recent data obtained by measurements of
      BrdU incorporation in T lymphocytes in humans (Kovacs et al., J. Exp. Med. 194
      (2001) 1731). The average telomere length of PBMC was calculated as the average
      length of these two subpopulations. The model fitted our experimental data well
      and allowed to derive a characteristic time of conversion of the rapidly
      proliferating cells to slowly proliferating cells on the order of 20 days. The
      half-life of the slowly proliferating cells was estimated to be about 6 months,
      which is in good agreement with data obtained by independent methodologies.
      Comparison of the one-population and two-subpopulations models demonstrated that
      one population model cannot explain the observed parameters of the terminal
      restriction fragment (TRF) dynamics while two-subpopulations model does. These
      results suggest that the rapid telomere shortening in infants is largely
      determined by the faster PBMC turnover compared to adults. This may have major
      implications for elucidation of the HIV pathogenesis in infants. One can
      speculate that the more rapid course of the HIV disease in infants is due to the
      existence of rapidly dividing cells, which are susceptible to HIV infection. In
      addition, these results could have implications for understanding of mechanisms
      of aging.

PMID- 14643187
TI  - Phenotypic plasticity can potentiate rapid evolutionary change.
AB  - Using a computational model of string-like haploid genotypes, we verify the
      conjecture (J. Theor. Biol. 188 (1997) 153) that phenotypic plasticity can speed
      up evolution. The corresponding real-life situation was realized by Waddington in
      experiments carried out on the fruit fly Drosophila. Waddington found that after
      selecting for an environmentally induced trait over a number of generations, a
      new, true-breeding phenotype resulted that was absent in the starting population.
      The phenomenon, termed 'genetic assimilation', continues to attract interest
      because of the rapidity of the effect and because of its seemingly Lamarckian
      implications. By making use of a genetic algorithm-based approach developed
      previously, we show that conventional Darwinian selection acting on regulatory
      genes can account for genetic assimilation. The essential assumption in our model
      is that a structural gene can be in either of three allelic states. These
      correspond to its being (a) 'on' or 'off' constitutively or (b) in a plastic
      state in which the probability that it is 'on' or 'off' is influenced by
      regulatory loci in a dosage-dependent manner.

PMID- 14643188
TI  - Coexistence of a sexual and an unisexual form stabilized by parasites.
AB  - An unisexual species (either parthenogenetic or gynogenetic form) often coexists
      sympatrically with a closely related anisogamous sexual species, forming a
      unisexual complex. This is puzzling because, all else being equal, a sexual
      population with the two-fold cost of sex (or the cost of producing males) cannot
      coexist with a unisexual population. This suggests that some ecological processes
      are at work to make possible the coexistence of the unisexual complex. Field and
      laboratory studies suggest that parasitism in a gynogenetic complex of the
      Japanese crucian carp (Carassius auratus) may play an important role in realizing
      the coexistence by giving frequency-dependent benefit to sexual population. Here,
      we study the simple dynamics of host-parasite interactions in which non-specific
      immune reaction of a sexual host is more effective than that of an unisexual
      host. We simply assume that the infective individuals are sterile. Stable
      coexistence of a unisexual species with their sexual relative is possible if
      pathogens are virulent and if the susceptibility of the unisexual form is more
      than twice as high as that of the sexual form. The coexistence is more difficult,
      when the fertility of males is relatively low in gynogenetic complexes. This
      implies that the coexistence of gynogenetic complexes is more difficult than that
      of parthenogenetic complexes in which parthenogenesis has no constraint on males.
      We conclude that parasitism is a promising candidate mechanism for the
      coexistence of unisexual complexes.

PMID- 14643189
TI  - Analysis of a one-dimensional random walk with irreversible losses at each step:
      applications for protein movement on DNA.
AB  - We analysed a one-dimensional random walk between two points when the migrating
      particle could be irreversibly lost (dissociated) from the system at each step of
      the process. We show that in the case of losses at each step the average number
      of steps made by the particle that reaches the final point does not obey
      quadratic dependence on the distance between the starting and the final points:
      for long distances this dependence is linear. This is because losses "select" for
      shorter pathways between the starting and the final points. We applied this
      analysis to protein translocations within long DNA molecules.

PMID- 14643190
TI  - Evolutionary dynamics of invasion and escape.
AB  - Whenever life wants to invade a new habitat or escape from a lethal selection
      pressure, some mutations may be necessary to yield sustainable replication. We
      imagine situations like (i) a parasite infecting a new host, (ii) a species
      trying to invade a new ecological niche, (iii) cancer cells escaping from
      chemotherapy, (iv) viruses or microbes evading anti-microbial therapy, and also
      (v) the repeated attempts of combinatorial chemistry in the very beginning of
      life to produce self-replicating molecules. All such seemingly unrelated
      situations have a common structure in terms of Darwinian dynamics: a replicator
      with a basic reproductive ratio less than one attempts to find some mutations
      that allow indefinite survival. We develop a general theory, based on multitype
      branching processes, to describe the evolutionary dynamics of invasion and
      escape.

PMID- 14643191
TI  - Cell sorting by differential cell motility: a model for pattern formation in
      Dictyostelium.
AB  - In the slug stage of the cellular slime mold Dictyostelium discoideum, prespore
      cells and four types of prestalk cells show a well-defined spatial distribution
      in a migrating slug. We have developed a continuous mathematical model for the
      distribution pattern of these cell types based on the balance of force in
      individual cells. In the model, cell types are assumed to have different
      properties in cell motility, i.e. different motive force, the rate of resistance
      against cell movement, and diffusion coefficient. Analysis of the stationary
      solution of the model shows that combination of these parameters and slug speed
      determines the three-dimensional shape of a slug and cell distribution pattern
      within it. Based on experimental data of slug motive force and velocity
      measurements, appropriate sets of parameters were chosen so that the cell-type
      distribution at stationary state matches the distribution in real slugs. With
      these parameters, we performed numerical calculation of the model in two
      dimensional space using a moving particle method. The results reproduced many of
      the basic features of slug morphogenesis, i.e. cell sorting, translocation of the
      prestalk region, elongation of the slug, and its steady migration.

PMID- 14643192
TI  - Estimating local interaction from spatiotemporal forest data, and Monte Carlo
      bias correction.
AB  - We point out a general problem in fitting continuous time spatially explicit
      models to a temporal sequence of spatial data observed at discrete times. To
      illustrate the problem, we examined the continuous time Markov model for forest
      gap dynamics. A forest is assumed to be apportioned into discrete cells (or
      sites) arranged in a regular square lattice. Each site is characterized as either
      a gap or a non-gap site according to the vegetation height of trees. The model
      incorporates the influence of neighboring sites on transition rate: transition
      rate from a non-gap to a gap site increases linearly with the number of neighbors
      that are currently in the gap state, and vice versa. We fitted the model to the
      spatiotemporal data of canopy height observed at the permanent plot in Barro
      Colorado Island (BCI). When we used the approximate maximum likelihood method to
      estimate the parameters of the model, the estimated transition rates included a
      large bias-in particular, the strength of interaction between nearby sites was
      underestimated. This bias originated from the assumption that each transition
      between two observation times is independent. The interaction between sites at
      local scale creates a long chain of transitions within a single census interval,
      which violates the independence of each transition. We show that a computer
      intensive method, called Monte Carlo bias correction (MCBC), is very effective in
      removing the bias included in the estimate. The global and local gap densities
      measuring spatial aggregation of gap sites were computed from simulated and real
      gap dynamics to assess the model. When the approximate likelihood estimates were
      applied to the model, the predicted local gap density was clearly lower than the
      observed one. The use of MCBC estimates, suggesting a strong interaction between
      sites, improved this discrepancy.

PMID- 14643193
TI  - Kinetic analysis of the attachment of a biological particle to a surface by
      macromolecular binding.
AB  - Motivated by the problem of microbial deposition, a dynamic model is developed
      for the attachment of a Brownian particle to a surface mediated by colloidal
      forces as well as macromolecular bridging. The model predicts the attachment
      probability of the particle to the surface based upon the free energy as a
      function of fluctuating bond number and separation distance from the surface.
      From this model, the mean first-passage time approach is used to predict the mean
      time required for the particle moving from the unattached state to the attached
      state based on the properties of the binding macromolecules. This approach
      provides an analytical approximation for mean transition time from the secondary
      energy minimum as well as the attachment rate constant for the general case where
      neither binding nor particle diffusion are necessarily rate-limiting.

PMID- 14643194
TI  - Three-dimensional reconstruction of hibiscus chlorotic ringspot virus.
AB  - Hibiscus chlorotic ringspot virus (HCRSV) is a positive-sense, single-stranded
      RNA virus, which belongs to the Tombusviridae family and infects plants of the
      Hibiscus genus, including kenaf, a woody plant of agricultural importance. These
      icosahedral viruses have a capsid consisting of 180 copies of coat protein (CP)
      arranged with T=3 symmetry. The CP consists of an internal RNA-binding domain, a
      shell-forming domain and a protruding domain. The HCRSV virion was reconstructed
      to about 12A resolution from cryo-EM images using the program EMAN. The structure
      had the arrangement of 90 dimers of protruding domains characteristic of the
      Tombusviridae. Reconstructions were also made from negatively stained samples,
      and showed essentially the same features. In addition, a particle of a different,
      "smooth" appearance was also identified in the negatively stained samples. These
      particles were slightly smaller and lacked protruding domains. Biochemical
      analysis confirmed the presence of two protein products: a 37 kDa protein
      identified as HCRSV CP and a 54 kDa protein that appeared to be of non-HCRSV
      origin.

PMID- 14643195
TI  - Cellulose orientation at the surface of the Arabidopsis seedling. Implications
      for the biomechanics in plant development.
AB  - In diffuse growing cells the orientation of cellulose fibrils determines
      mechanical anisotropy in the cell wall and hence also the direction of plant and
      organ growth. This paper reports on the mean or net orientation of cellulose
      fibrils in the outer epidermal wall of the whole Arabidopsis plant. This outer
      epidermal wall is considered as the growth-limiting boundary between plant and
      environment. In the root a net transverse orientation of the cellulose fibrils
      occurs in the elongation zone, while net random and longitudinal orientations are
      found in subsequent older parts of the differentiation zone. The position and the
      size of the transverse zone is related with root growth rate. In the shoot the
      net orientation of cellulose fibrils is transverse in the elongating apical part
      of the hypocotyl, and longitudinal in the fully elongated basal part. Leaf
      primordia and very young leaves have a transverse orientation. Throughout further
      development the leaf epidermis builds a very complex pattern of cells with a
      random orientation and cells with a transverse or a longitudinal orientation of
      the cellulose fibrils. The patterns of net cellulose orientation correlate well
      with the cylindrical growth of roots and shoots and with the typical planar
      growth of the leaf blade. On both the shoot and the root surface very specific
      patterns of cellulose orientation occur at sites of specific cell
      differentiation: trichome-socket cells complexes on the shoot and root hairs on
      the root.

PMID- 14643196
TI  - Nanostructural features of demosponge biosilica.
AB  - Recent interest in the optical and mechanical properties of silica structures
      made by living sponges, and the possibility of harnessing these mechanisms for
      the synthesis of advanced materials and devices, motivate our investigation of
      the nanoscale structure of these remarkable biomaterials. Scanning electron and
      atomic force microscopic (SEM and AFM) analyses of the annular substructure of
      demosponge biosilica spicules reveals that the deposited material is
      nanoparticulate, with a mean particle diameter of 74+/-13 nm. The nanoparticles
      are deposited in alternating layers with characteristic etchant reactivities.
      Further analyses of longitudinally fractured spicules indicate that each
      deposited layer is approximately monoparticulate in thickness and exhibits
      extensive long range ordering, revealing an unanticipated level of nanoscale
      structural complexity. NMR data obtained from differentially heated spicule
      samples suggest that the etch sensitivity exhibited by these annular domains may
      be related to variation in the degree of silica condensation, rather than
      variability in the inclusion of organics. In addition, AFM phase imaging in
      conjunction with results obtained from HF and alkaline etching experiments
      suggest that at various stages in spicule biosynthesis, regions of unusually low
      silica condensation are deposited, indicating a possible interruption in normal
      spicule formation. While this discovery of nanoparticulate silica aggregation in
      demosponge skeletal elements is likely to reflect the intrinsic kinetic tendency
      of silica to form such particles during polycondensation, the heirarchical
      organization of these nanoparticles is biologically unique.

PMID- 14643197
TI  - Three-dimensional microarchitecture of the plates (primary, secondary, and
      carinar process) in the developing tooth of Lytechinus variegatus revealed by
      synchrotron X-ray absorption microtomography (microCT).
AB  - This paper reports the first noninvasive, volumetric study of entire cross
      sections of a sea urchin tooth in which the individual calcite structural
      elements could be resolved. Two cross-sectionally intact fragments of a
      Lytechinus variegatus tooth were studied with synchrotron microCT (microcomputed
      tomography) with 1.66 microm voxels (volume elements). These fragments were from
      the plumula, that is the tooth zone with rapidly increasing levels of mineral;
      one fragment was from a position aboral of where the keel developed and the
      second was from the zone where the keel was developing. The primary plates,
      secondary plates, carinar process plates, prisms, and elements of the lamellar
      needle complex were resolved. Comparison of the microCT data with optical
      micrographs of stained thin sections confirmed the identifications and measured
      dimensions of the characteristic microarchitectural features. The interplay of
      reinforcing structures (plates and prisms) was more clearly revealed in the
      volumetric numerical data sets than in single or sequential slices. While it is
      well known that the primary plates and prisms in camarodont teeth are situated to
      improve resistance to bending (which can be termed primary bending), the data
      presented provide a new understanding of the mechanical role of the carinar
      process plates, that is, a geometry consistent with that required in the keel to
      resist lateral or transverse bending of the tooth about a second axis. The
      increase in robustness of teeth incorporating lateral keel reinforcement suggests
      that the relative development of carinar processes (toward a geometry similar to
      that of L. variegatus) is a character which can be used to infer which sea
      urchins among the stirodonts are most primitive and among the camarodonts which
      are more primitive.

PMID- 14643198
TI  - Automated three-dimensional reconstruction of keyhole limpet hemocyanin type 1.
AB  - We have reconstructed a three-dimensional map of keyhole limpet hemocyanin
      isoform 1 (KLH1), using our automated data collection software, Leginon,
      integrated with particle selection algorithms, and the SPIDER reconstruction
      package. KLH1, a 7.9 MDa macromolecule, is an extracellular respiratory pigment
      composed of two asymmetric decamers, and presents an overall D(5) point-group
      symmetry. The reconstruction is in agreement with previous data published on
      molluscan hemocyanins. The reconstructed map (11.3A resolution, 3sigma criterion)
      was used to fit an available X-ray crystallography structure of Octopus dofleini
      Odg, solved at 2.3A [J. Mol. Biol. 278 (4) (1998) 855], with satisfactory
      results. The results validate the approach of automating the cryoEM process and
      demonstrate that the quality of the images acquired and the particles selected is
      comparable to those obtained using manual methods. Several problems remain to be
      solved however before these results can be generalized.

PMID- 14643199
TI  - Crystal structure of SecB from Escherichia coli.
AB  - The chaperone SecB from Escherichia coli is primarily involved in passing
      precursor proteins into the Sec system via specific interactions with SecA. The
      crystal structure of SecB from E. coli has been solved to 2.35 A resolution. The
      structure shows flexibility in the crossover loop and the helix-connecting loop,
      regions that have been implicated to be part of the SecB substrate-binding site.
      Moreover conformational variability of Trp36 is observed as well as different
      loop conformations for the different monomers. Based on this, we speculate that
      SecB can regulate the access or extent of its hydrophobic substrate-binding site,
      by modulating the conformation of the crossover loop and the helix-connecting
      loop. The structure also clearly explains why the tetrameric equilibrium is
      shifted towards the dimeric state in the mutant SecBCys76Tyr. The buried cysteine
      residue is crucial for tight packing, and mutations are likely to disrupt the
      tetramer formation but not the dimer formation.

PMID- 14643200
TI  - Projection structure of the bacterial oxalate transporter OxlT at 3.4A
      resolution.
AB  - OxlT is a bacterial transporter protein with 12 transmembrane segments that
      belongs to the Major Facilitator Superfamily of transporters. It facilitates the
      exchange of oxalate and formate across the membrane of the Gram-negative
      bacterium Oxalobacter formigenes. From an electron crystallographic analysis of
      two-dimensional, tube-like crystals of OxlT, we have previously determined the
      three-dimensional structure of this transporter at 6.5 A resolution. Here, we
      report conditions to obtain crystalline, two-dimensional sheets of OxlT with
      diameters exceeding 2 microm. Images of the crystalline sheets were recorded at
      liquid nitrogen temperatures on a transmission electron microscope equipped with
      a field-emission gun, operated at 300 kV. Computed optical diffraction patterns
      from the best images display measurable reflections to about 3.4A, and electron
      diffraction patterns show spots to about 3.2 A resolution in the best cases. As
      in the case of the tube-like crystals, the new crystalline sheets also belong to
      the p22(1)2(1) symmetry group. However, the unit cell dimensions of 102.7A x 67.3
      A are significantly smaller in one direction than those previously observed with
      the tube-like crystals that display unit cell dimensions of 100.3A x 79.0 A.
      Different regions of OxlT are involved in intermolecular contacts in the two
      types of crystals, and the improved resolution of the sheet crystals appears to
      be mainly attributable to this tighter packing of the monomers within the unit
      cell.

PMID- 14643201
TI  - The relations between neurite development and the subcellular structures of
      hippocampal neuron somata.
AB  - The relations between neurite development and the subcellular structures of the
      hippocampal neuron somata have been studied with atomic force microscopy (AFM).
      The conformation of the neuron was achieved by the synapse-like structures found
      by AFM scanning along a neurite of the cell. Hippocampal neuron somata were
      divided into two or three subcellular parts by one or two horizontal grooves. The
      upper parts increased while the middle and the lower parts decreased with the
      number and the length of the neurites and the formation of the neurosynapse-like
      structures. When neurites sufficiently developed, the middle parts were lost and
      the lower parts became very small. Mitosis inhibitors could prevent the formation
      of such subcellular structures of hippocampal neuron somata, which was
      accompanied by the loss of ability to form synapse-like structures. These results
      suggest that the upper parts are responsible for neuritogenesis while the middle
      and the lower parts only have indirect effect on it.

PMID- 14643202
TI  - The crystal structure of murine p97/VCP at 3.6A.
AB  - p97/VCP is a member of the AAA ATPase family and has roles in both membrane
      fusion and ubiquitin dependent protein degradation. Here, we present a 3.6A
      crystal structure of murine p97 in which D2 domain has been modelled as poly
      alanine and the remaining approximately 100 residues are absent. The resulting
      structure illustrates a head-to-tail packing arrangement of the two p97 AAA
      domains in a natural hexameric state with D1 ADP bound and D2 nucleotide free.
      The head-to-tail packing arrangement observed in this structure is in contrast to
      our previously predicted tail-to-tail packing model. The linker between the D1
      and D2 domains is partially disordered, suggesting a flexible nature. Normal mode
      analysis of the crystal structure suggests anti-correlated motions and distinct
      conformational states of the two AAA domains.

PMID- 14643203
TI  - Extended knobs-into-holes packing in classical and complex coiled-coil
      assemblies.
AB  - This year marks the 50th anniversary of Crick's seminal paper on the packing of
      alpha-helices into coiled-coil structures. The central tenet of Crick's work is
      the interdigitation of side chains, which directs the helix-helix interactions;
      so called knobs-into-holes packing. Subsequent determinations of coiled-coil
      protein sequences and structures confirmed the key features of Crick's model and
      established it as a fundamental concept in structural biology. Recently, we
      developed a program, SOCKET, to recognise knobs-into-holes packing in protein
      structures, which we applied to the Protein Data Bank to compile a database of
      coiled-coil structures. In addition to classic structures, the database reveals 4
      helix bundles and larger helical assemblies. Here, we describe how the more
      complex structures can be understood by extending Crick's principles for classic
      coiled coils. In the simplest case, each helix of a 2-stranded structure
      contributes a single seam of (core) knobs-into-holes to the helical interface. 3
      , 4-, and 5-Stranded structures, however, are best considered as rings of helices
      with cycles of knobs-into-holes. These higher-order oligomers make additional
      (peripheral) knobs-into-holes that broaden the helical contacts. Combinations of
      core and peripheral knobs may be assigned to different sequence repeats offset
      within the same helix. Such multiple repeats lead to multi-faceted helices, which
      explain structures above dimers. For instance, coiled-coil oligomer state
      correlates with the offset of the different repeats along a sequence. In
      addition, certain multi-helix assemblies can be considered as conjoined coiled
      coils in which multi-faceted helices participate in more than one coiled-coil
      motif.

PMID- 14643204
TI  - Analytical methods and software tools for macromolecular microscopy.

PMID- 14643205
TI  - Iplt--image processing library and toolkit for the electron microscopy community.
AB  - We present the foundation for establishing a modular, collaborative, integrated,
      open-source architecture for image processing of electron microscopy images,
      named iplt. It is designed around object oriented paradigms and implemented using
      the programming languages C++ and Python. In many aspects it deviates from
      classical image processing approaches. This paper intends to motivate developers
      within the community to participate in this on-going project. The iplt homepage
      can be found at http://www.iplt.org.

PMID- 14643206
TI  - On the three-dimensional reconstruction of icosahedral particles.
AB  - The problem of reconstructing an isolated particle from its projections, using
      spherical harmonics to represent the scattering density, is reformulated. A
      technique that makes explicit and efficient use of the symmetry to describe the
      angular part of the scattering density is developed in full detail for the
      particular case of icosahedral symmetry. It provides a very concise method, where
      the effort is concentrated in the determination of the radial part of the Fourier
      transform of the particle scattering density. The method allows individual-image
      model-independent view determination. An illustrative numerical example is given.

PMID- 14643207
TI  - A statistical approach to computer processing of cryo-electron microscope images:
      virion classification and 3-D reconstruction.
AB  - The scattering density of the virus is represented as a truncated weighted sum of
      orthonormal basis functions in spherical coordinates, where the angular
      dependence of each basis function has icosahedral symmetry. A statistical model
      of the image formation process is proposed and the maximum likelihood estimation
      method computed by an expectation-maximization algorithm is used to estimate the
      weights in the sum and thereby compute a 3-D reconstruction of the virus
      particle. If multiple types of virus particle are represented in the boxed images
      then multiple 3-D reconstructions are computed simultaneously without first
      requiring that the type of particle shown in each boxed image be determined.
      Examples of the procedure are described for viruses with known structure: (1). 3
      D reconstruction of Flockhouse Virus from experimental images, (2). 3-D
      reconstruction of the capsid of Nudaurelia Omega Capensis Virus from synthetic
      images, and (3). 3-D reconstruction of both the capsid and the procapsid of
      Nudaurelia Omega Capensis Virus from a mixture of unclassified synthetic images.

PMID- 14643208
TI  - 2D fast rotational matching for image processing of biophysical data.
AB  - In 3D single particle reconstruction, which involves the translational and
      rotational matching of a large number of electron microscopy (EM) images, the
      algorithmic performance is largely dependent on the efficiency and accuracy of
      the underlying 2D image alignment kernel. We present a novel fast rotational
      matching kernel for 2D images (FRM2D) that significantly reduces the cost of this
      alignment. The alignment problem is formulated using one translational and two
      rotational degrees of freedom. This allows us to take advantage of fast Fourier
      transforms (FFTs) in rotational space to accelerate the search of the two angular
      parameters, while the remaining translational parameter is explored, within a
      limited range, by exhaustive search. Since there are no boundary effects in FFTs
      of cyclic angular variables, we avoid the expensive zero padding associated with
      Fourier transforms in linear space. To verify the robustness of our method,
      efficiency and accuracy tests were carried out over a range of noise levels in
      realistic simulations of EM images. Performance tests against two standard
      alignment methods, resampling to polar coordinates and self-correlation,
      demonstrate that FRM2D compares very favorably to the traditional methods. FRM2D
      exhibits a comparable or higher robustness against noise and a significant gain
      in efficiency that depends on the fineness of the angular sampling and linear
      search range.

PMID- 14643209
TI  - A fast reconstruction algorithm for electron microscope tomography.
AB  - We have implemented a Fast Fourier Summation algorithm for tomographic
      reconstruction of three-dimensional biological data sets obtained via
      transmission electron microscopy. We designed the fast algorithm to reproduce
      results obtained by the direct summation algorithm (also known as filtered or R
      weighted backprojection). For two-dimensional images, the new algorithm scales as
      O(N(theta)M log M)+O(MN log N) operations, where N(theta) is the number of
      projection angles and M x N is the size of the reconstructed image. Three
      dimensional reconstructions are constructed from sequences of two-dimensional
      reconstructions. We demonstrate the algorithm on real data sets. For typical
      sizes of data sets, the new algorithm is 1.5-2.5 times faster than using direct
      summation in the space domain. The speed advantage is even greater as the size of
      the data sets grows. The new algorithm allows us to use higher order spline
      interpolation of the data without additional computational cost. The algorithm
      has been incorporated into a commonly used package for tomographic
      reconstruction.

PMID- 14643210
TI  - Focal pair merging for contrast enhancement of single particles.
AB  - A common technique in transmission electron microscopy is the collection of a
      focal pair, in which the first, close to focus image contains higher resolution
      information at lower contrast, and the second, far from focus image has high
      contrast but less reliable high-resolution information. Typically these second
      micrographs are used for purposes of particle selection, orientation estimate or
      micrograph evaluation. We introduce a technique for merging the information from
      both images, including signal to noise ratio weighting, contrast transfer
      function correction, and optional Weiner filtration. This produces a composite
      image with reduced contrast transfer function artifacts and optimized contrast.
      This technique is useful in numerous cases where low-contrast images are
      produced, such as small particles, proteins solubilized in detergent or projects
      with high-resolution goals when the first image is taken very close to focus.

PMID- 14643211
TI  - Automated determination of parameters describing power spectra of micrograph
      images in electron microscopy.
AB  - The current theory of image formation in electron microscopy has been semi
      quantitatively successful in describing data. The theory involves parameters due
      to the transfer function of the microscope (defocus, spherical aberration
      constant, and amplitude constant ratio) as well as parameters used to describe
      the background and attenuation of the signal. We present empirical evidence that
      at least one of the features of this model has not been well characterized.
      Namely the spectrum of the noise background is not accurately described by a
      Gaussian and associated "B-factor;" this becomes apparent when one studies high
      quality far-from focus data. In order to have both our analysis and conclusions
      free from any innate bias, we have approached the questions by developing an
      automated fitting algorithm. The most important features of this routine, not
      currently found in the literature, are (i). a process for determining the cutoff
      for those frequencies below which observations and the currently adopted model
      are not in accord, (ii). a method for determining the resolution at which no more
      signal is expected to exist, and (iii). a parameter-with units of spatial
      frequency-that characterizes which frequencies mainly contribute to the signal.
      Whereas no general relation is seen to exist between either of these two
      quantities and the defocus, a simple empirical relationship approximately relates
      all three.

PMID- 14643212
TI  - Fast 3D motif search of EM density maps using a locally normalized cross
      correlation function.
AB  - Three-dimensional motif search is becoming increasingly important both in the
      search for molecular signatures within a tomographic reconstruction, at low
      resolution, and in the search for atomic structures within high-resolution cryo
      EM maps of macromolecular complexes. The present work describes the
      implementation of a fast local correlation algorithm suitable for template
      matching in the SPIDER environment. Two examples are given, one in each of the
      areas of application: (i). within a 7.8A single-particle reconstruction of the
      Escherichia coli ribosome, four proteins and one RNA structure were located with
      high accuracy; (ii). within a cryo-tomogram of sarcoplasmic reticulum vesicles,
      ryanodine receptors were located in positions that agreed with expert knowledge.

PMID- 14643213
TI  - FEMME database: topologic and geometric information of macromolecules.
AB  - FEMME (Feature Extraction in a Multi-resolution Macromolecular Environment:
      http://www.biocomp.cnb.uam.es/FEMME/) database version 1.0 is a new
      bioinformatics data resource that collects topologic and geometric information
      obtained from macromolecular structures solved by three-dimensional electron
      microscopy (3D-EM). Although the FEMME database is focused on medium resolution
      data, the methodology employed (based on the so-called alpha-shape theory) is
      applicable to atomic resolution data as well. The alpha-shape representation
      allows the automatic extraction of structural features from 3D-EM volumes and
      their subsequent characterisation. FEMME is being populated with 3D-EM data
      stored in the electron microscopy database EMD-DB (http://www.ebi.ac.uk/msd/).
      However, and since the number of entries in EMD-DB is still relatively small,
      FEMME is also being populated in this initial phase with structural data from PDB
      and PQS databases (http://www.rcsb.org/pdb/ and pqs.ebi.ac.uk/, respectively)
      whose resolution has been lowered accordingly. Each FEMME entry contains
      macromolecular geometry and topology information with a detailed description of
      its structural features. Moreover, FEMME data have facilitated the study and
      development of a method to retrieve macromolecular structures by their structural
      content based on the combined use of spin images and neural networks with
      encouraging results. Therefore, the FEMME database constitutes a powerful tool
      that provides a uniform and automatic way of analysing volumes coming from 3D-EM
      that will hopefully help the scientific community to perform wide structural
      comparisons.

PMID- 14643214
TI  - Applications of a bilateral denoising filter in biological electron microscopy.
AB  - Due to the sensitivity of biological sample to the radiation damage, the low dose
      imaging conditions used for electron microscopy result in extremely noisy images.
      The processes of digitization, image alignment, and 3D reconstruction also
      introduce additional sources of noise in the final 3D structure. In this paper,
      we investigate the effectiveness of a bilateral denoising filter in various
      biological electron microscopy applications. In contrast to the conventional low
      pass filters, which inevitably smooth out both noise and structural features
      simultaneously, we found that bilateral filter holds a distinct advantage in
      being capable of effectively suppressing noise without blurring the high
      resolution details. In as much, we have applied this technique to individual
      micrographs, entire 3D reconstructions, segmented proteins, and tomographic
      reconstructions.

PMID- 14643215
TI  - Interactive fitting augmented by force-feedback and virtual reality.
AB  - The synthesis of low-resolution electron microscopy data with high-resolution
      molecular structures has become a common routine in the modeling of biomolecular
      assemblies. In contrast to algorithmic "black box" solutions, the interactive
      "fitting by eye" takes advantage of an expert's structural or biochemical
      knowledge and can be used with very noisy experimental data. In the solution
      proposed in this paper, we support the expert user in an interactive fitting
      session by haptic rendering and virtual reality. The quantitative and tactile
      feedback facilitates and objectifies the otherwise unrestrained modeling. We
      introduce a highly accurate reduced representation of the gradient of the cross
      correlation coefficient that sustains force updates for haptic rendering at
      sufficiently high refresh rates.

PMID- 14643216
TI  - Volumetric feature extraction and visualization of tomographic molecular imaging.
AB  - Electron tomography is useful for studying large macromolecular complex within
      their cellular context. The associate problems include crowding and complexity.
      Data exploration and 3D visualization of complexes require rendering of tomograms
      as well as extraction of all features of interest. We present algorithms for
      fully automatic boundary segmentation and skeletonization, and demonstrate their
      applications in feature extraction and visualization of cell and molecular
      tomographic imaging. We also introduce an interactive volumetric exploration and
      visualization tool (Volume Rover), which encapsulates implementations of the
      above volumetric image processing algorithms, and additionally uses efficient
      multi-resolution interactive geometry and volume rendering techniques for
      interactive visualization.

PMID- 14643217
TI  - Low-resolution structure refinement in electron microscopy.
AB  - A real-space structure refinement method, originally developed for macromolecular
      X-ray crystallography, has been applied to protein structure analysis by electron
      microscopy (EM). This method simultaneously optimizes the fit of an atomic model
      to a density map and the stereo-chemical properties of the model by minimizing an
      energy function. The performance of this method is characterized at different
      resolution and signal-to-noise ratio conditions typical for EM electron density
      maps. A multi-resolution scheme is devised to improve the convergence of the
      refinement on the global energy minimum. Applications of the method to various
      model systems are demonstrated here. The first case is the arrangement of FlgE
      molecules in the helical filament of flagellar hook, in which refinement with
      segmented rigid bodies improves the density correlation and reduces severe van
      der Waals contacts among the symmetry-related subunits. The second case is a
      conformational analysis of the NSF AAA ATPase in which a multi-conformer model is
      used in the refinement to investigate the arrangement of the two ATPase domains
      in the molecule. The third case is a docking simulation in which the crystal
      structure of actin and the NOE data from NMR experiments on the dematin headpiece
      are combined with a low-resolution EM density map to generate an atomic model of
      the F-actin-dematin headpiece structure.

PMID- 14643218
TI  - An improved algorithm for anisotropic nonlinear diffusion for denoising cryo
      tomograms.
AB  - Cryo-electron tomography is an imaging technique with an unique potential for
      visualizing large complex biological specimens. It ensures preservation of the
      biological material but the resulting cryotomograms are extremely noisy.
      Sophisticated denoising techniques are thus essential for allowing the
      visualization and interpretation of the information contained in the
      cryotomograms. Here a software tool based on anisotropic nonlinear diffusion is
      described for filtering cryotomograms. The approach reduces local noise and
      meanwhile enhances both curvilinear and planar structures. In the program a novel
      solution of the partial differential equation has been implemented, which allows
      a reliable estimation of derivatives and, furthermore, reduces computation time
      and memory requirements. Several criteria have been included to automatically
      select the optimal stopping time. The behaviour of the denoising approach is
      tested for visualizing filamentous structures in cryotomograms.

PMID- 14643219
TI  - Issues of resolution and polymorphism in single-particle reconstruction.
AB  - Three-dimensional reconstruction from electron microscopic (EM) images of
      isolated macromolecular complexes is being employed by many laboratories. This
      approach is extremely powerful and continues to improve in resolution. In the
      absence of stereochemical constraints that can be used to assess the quality of a
      reconstruction, as exist in X-ray crystallography, several other measures have
      typically been used. A very useful assessment of quality can be made in the
      comparison between the projections of the three-dimensional reconstruction and
      averages generated from classes of images. The main quantitative measure has been
      that of resolution statistics, typically based upon Fourier shell correlations.
      We show, using only simulated noise for images, that impressive resolution
      statistics are generated that can even extend the apparent resolution of the
      starting model. When truly independent reconstructions are generated starting
      from different initial models, however, such artefacts are not possible. We also
      show, using real images of DnaB rings, that in the presence of polymorphism
      artefactual reconstructions can be generated whose projections match class
      averages. These averages, however, are themselves artefactual as they involve
      heterogeneous images. The issues presented here need to be considered when single
      particle EM reconstructions are evaluated.

PMID- 14643220
TI  - Windex: a toolset for indexing helices.
AB  - We describe here a set of procedures and algorithms that may be used as an aid in
      determining the indexing rule of a helical specimen. Crystallizing macromolecules
      into helical arrays has the potential to speed up and simplify the process of
      three-dimensional reconstruction of the macromolecular structure. The process of
      helical reconstruction has been largely automated except for the critical first
      step of indexing the helical diffraction pattern. This is quite often the rate
      limiting step in the overall process, particularly in the case of large helical
      tubes, which have complicated helical diffraction patterns that may vary from
      tube to tube. We have developed a set of procedures, supported by a graphical
      user interface, that provide a straightforward and semi-automated approach to
      indexing a helical structure. The new procedures have been tested using a number
      of helical specimens, including TMV, acto-myosin, decorated microtubules, and a
      variety of helical tubes of a bacterial membrane protein.

PMID- 14643221
TI  - GUI programs for processing individual images in early stages of helical image
      reconstruction--for high-resolution structure analysis.
AB  - A set of programs equipped with graphical user interface has been developed for
      processing individual images in early stages of the three-dimensional helical
      image reconstruction procedure. These programs can be used for initial screening
      of suitable image area, straightening the object image, determination of box
      parameters including the repeat distance, determination of the out-of-plane tilt
      and initial editing of the layer-line data. These tasks are difficult to automate
      and therefore very time-consuming. The programs, developed by adopting the
      concept of the layer-line indexing [Ultramicroscopy 84 (2000) 1-14], are
      effective for processing many images of filamentous molecular assemblies and
      especially tubular crystals having various helical classes. Using these programs,
      higher-resolution signals can be extracted more reliably and quickly, and the
      time required for processing each image can be reduced to 1/2-1/10. Here also
      presented is an overview on helical image reconstruction for high-resolution
      structure analysis.

PMID- 14643222
TI  - Cross-correlation and merging of crystallographic reflections derived from
      cryoelectron micrographs of 3D crystals: application to the Limulus acrosomal
      bundle.
AB  - A method is described for merging in reciprocal space of electron microscopic
      data from three-dimensional crystals of the acrosomal bundle. Permutation of
      indices was required to find the proper alignment of data from different bundles.
      The method utilizes a statistical evaluation of the significance of the cross
      correlation results to indicate the proper order for merging. The three
      dimensional (3D) merging is a reference-free operation that does not depend on
      choosing a "zero-tilt" user-defined starting point. Results from the merging are
      given and the merged 3D data to 9.5A resolution is evaluated for coherence.
      General issues such as statistical significance of cross-correlation function
      peaks, symmetry evaluation, and phase coherence as a function of amplitude are
      discussed.

PMID- 14643223
TI  - Three-dimensional diffractive imaging for crystalline monolayers with one
      dimensional compact support.
AB  - The use of a compact support constraint along the beam direction is considered as
      a solution to the phase problem for diffraction by two-dimensional protein
      crystals. Specifically we apply the iterative Gerchberg-Saxton-Fienup algorithm
      to simulated three-dimensional transmission electron diffraction data from
      monolayer organic crystals. We find that oversampling along the reciprocal
      lattice rods (relrods) normal to the monolayer alone does not solve the phase
      problem in this geometry in general. However, based on simulations for a
      crystalline protein monolayer (lysozyme), we find that convergence is obtained in
      three dimensions if phases are supplied from a few high resolution electron
      microscope images recorded at small tilts to the beam direction. In the absence
      of noise, amplitude-weighted phase residuals of around 5 degrees, and a cross
      correlation coefficient of 0.96 between the true and estimated potential are
      obtained if phases are included from images at tilts of up to 15 degrees. The
      performance is almost as good in the presence of noise at a level that is
      comparable to that commonly observed in electron crystallography of proteins. The
      method should greatly reduce the time and labor needed for data acquisition and
      analysis in cryo-electron microscopy of organic thin crystals by avoiding the
      need to record images at high tilt angles.

PMID- 14643224
TI  - Diffraction imaging of single particles and biomolecules.
AB  - Theory predicts that with a very short and very intense X-ray pulse, the image of
      a single diffraction pattern may be recorded from a large macromolecule, a virus,
      or a nanocluster of proteins without the need for a crystal. A three-dimensional
      data set can be assembled from such images when many copies of the molecule are
      exposed to the beam one by one in random orientations. We outline a method for
      structure reconstruction from such a data set in which no independent information
      is available about the orientation of the images. The basic requirement for
      reconstruction and/or signal averaging is the ability to tell whether two noisy
      diffraction patterns represent the same view of the sample or two different
      views. With this knowledge, averaging techniques can be used to enhance the
      signal and extend the resolution in a redundant data set. Based on statistical
      properties of the diffraction pattern, we present an analytical solution to the
      classification problem. The solution connects the number of incident X-ray
      photons with the particle size and the achievable resolution. The results are
      surprising in that they show that classification can be done with less than one
      photon per pixel in the limiting resolution shell, assuming Poisson-type photon
      noise in the image. The results can also be used to provide criteria for
      improvements in other image classification procedures, e.g., those used in
      electron tomography or diffraction.

PMID- 14643225
TI  - EMDep: a web-based system for the deposition and validation of high-resolution
      electron microscopy macromolecular structural information.
AB  - This paper describes the design and implementation of a Web-based deposition
      system, EMDep, for macro-molecular volumes determined by electron microscopy and
      deposited at the European Bioinformatics Institute (EBI) for inclusion in the
      Electron Microscopy Data Base (EMDB). EMDep is a flexible and portable system
      (http://www.ebi.ac.uk/msd-srv/emdep/) that allows for the acceptance and
      validation of data, by an interactive depositor-driven operation. The system
      takes full advantage of the knowledge and expertise of the experimenters, rather
      than relying on the database curators, for the complete and accurate description
      of the structural experiment and its results.

PMID- 14643226
TI  - Web portal to an image database for high-resolution three-dimensional
      reconstruction.
AB  - The exponential increase of image data in high-resolution reconstructions by
      electron cryomicroscopy (cryoEM) has posed a need for efficient data management
      solutions in addition to powerful data processing procedures. Although relational
      databases and web portals are commonly used to manage sequences and structures in
      biological research, their application in cryoEM has been limited due to the
      complexity in accomplishing the dual tasks of interacting with proprietary
      software and simultaneously providing data access to users without database
      knowledge. Here, we report our results in developing web portal to SQL image
      databases used by the Image Management and Icosahedral Reconstruction System
      (IMIRS) to manage cryoEM images for subnanometer-resolution reconstructions.
      Fundamental issues related to the design and deployment of web portals to image
      databases are described. A web browser-based user interface was designed to
      accomplish data reporting and other database-related services, including user
      authentication, data entry, graph-based data mining, and various query and
      reporting tasks with interactive image manipulation capabilities. With an
      integrated web portal, IMIRS represents the first cryoEM application that
      incorporates both web-based data reporting tools and a complete set of data
      processing modules. Our examples should thus provide general guidelines
      applicable to other cryoEM technology development efforts.

PMID- 14643227
TI  - A second generation apparatus for time-resolved electron cryo-microscopy using
      stepper motors and electrospray.
AB  - We describe here a second generation apparatus for studying transient reaction
      conformations in macromolecules and their complexes by electron cryo-microscopy.
      Reactions are trapped by rapid freezing in times ranging from a few milliseconds
      to tens of seconds after initiation. Blotting of the electron microscope grid and
      freezing it in liquid ethane uses computer controlled microstepping motors. For
      the fastest time resolution, a blotted grid containing a thin film of one
      reactant is sprayed with small droplets containing a second reactant just before
      freezing. The spray is produced electrically (electrospray), which gives a dense
      cloud of droplets <1 microm in diameter from the 1-2 microl of solution required
      per grid. A second method in which two solutions are first mixed by turbulent
      flow and then blotted prior to freezing is used for reactions with time courses
      >1s.

PMID- 14643228
TI  - Variability in goethite surface site density: evidence from proton and carbonate
      sorption.
AB  - Goethite is a representative iron oxide in natural environments due to its
      abundance and thermodynamic stability and may be responsible for many surface
      mediated processes, including ion retention and mobility in aqueous settings. A
      large variability in morphologies and specific surface areas of goethite crystals
      exists but little work has been done to compare surface reactivity between them.
      The present work offers experimental evidence for the existence of an inverse
      relationship between sorption capacity for protons and carbonate ions and
      specific surface area of goethite for three synthetic goethite preparations
      spanning surface area differences by a factor of 2. An explanation for this was
      found by assuming a variable reactive site density between preparations in direct
      relationship to their sorption capacity based on congruency of carbonate sorption
      computed on a per-site basis. Previous evidence of maximum sorption capacities
      supports this explanation, and site density ratios between the goethites studied
      here were obtained. Triple layer surface complexation modeling was successful in
      describing adsorption data for all goethite preparations using equal
      stoichiometries. A new formulation of standard state for activities of surface
      species based on a 1.0 mole fraction of sites on the solid allowed transformation
      of the conventional molar concentration-based affinity constants to values based
      on site occupancy. In this fashion, by applying the appropriate site density
      ratios, a single set of affinity constant values was found that described
      accurately the adsorption data for all preparations.

PMID- 14643229
TI  - Study of the adsorption of fibrinogen on gold-coated silicon wafer by an
      impedance method.
AB  - In 0.1 mol/l KH(2)PO(4)-Na(2)HPO(4) (pH 7.80) buffer solution, the potential of
      zero charge (PZC) and the open circuit potential of gold-coated silicon were
      determined to be about -0.6 and +0.10 V (vs SCE), respectively. The open circuit
      potential was higher than the PZC, which indicated that the surface of the gold
      coated electrode had a positive charge. The ellipsometry experiment showed that
      the adsorption of fibrinogen onto the gold-coated silicon wafer surface arrived
      at a saturated state when the adsorption time exceeded 50 min. The percentage of
      surface without adsorbed protein, theta, was about 63%. This means that the
      proportion of surface actually occupied by fibrinogen was only about 37% after
      the adsorption arrived at saturation. The solution/protein capacitance value was
      determined in an impulse state around -0.59 V (vs SCE) and was stable (4.2x10(-5)
      F) at other potentials.

PMID- 14643230
TI  - Sodium stearate adsorption onto titania pigment.
AB  - The interaction of sodium stearate with titania pigment particles from aqueous
      suspension has been investigated using thermal analysis and infrared spectroscopy
      combined with electrochemical studies. Thermogravimetric analysis (TGA) was used
      both to determine the adsorption isotherm and to investigate the interaction
      behavior. Monolayer coverage is determined to be 0.95 mg/m(2); however, unlike
      the case with organic solvents, multilayer adsorption occurs. Diffuse reflectance
      infrared Fourier transform (DRIFT) spectroscopy, combined with TGA, revealed that
      the surface monolayer is chemically bound. DRIFT spectroscopic data also
      indicated that the stearate bridged across two aluminum atoms. Subsequent
      stearate layers were physisorbed to the stearate monolayer and were readily
      removed with acetone washing.

PMID- 14643231
TI  - Further insights into the role of carbon surface functionalities in the mechanism
      of phenol adsorption.
AB  - The presented study describes the temperature as well as pH dependence of phenol
      adsorption (and adsorption kinetics) on four carbons with different chemical
      compositions of the surface layer but almost identical porosity. In the first
      part, it is shown, applying the most sophisticated method of carbon porosity
      characterization (i.e., the method of Do and co-workers-ND method), that the
      porosity does not change much after the chemical modification of carbons. Then it
      is shown that the ND method leads to the same results as the DFT (density
      functional theory) does. Next, the TPD results for D43/1 carbons (initial,
      modified with HNO(3), fuming H(2)SO(4), and with NH(3)) are described. The TPD
      results for carbon modified with fuming sulphuric acid has not been reported yet
      by others. The deconvolution of peaks is performed. The obtained results,
      together with those already published, lead to the chemical structures of surface
      functionalities for all studied carbons. The thermogravimetric analysis of phenol
      adsorption shows that the amount of chemically bonded molecules is small. Then it
      is shown that the adsorption at the acidic pH (1.5) level is lower for all
      studied carbons than that at the neutral one. The description of the isotherms
      applying adsorbability, quasi-Freundlich and DA models, together with enthalpy
      measurements, lead to the mechanism of phenol adsorption at both pH values. The
      mechanism is, furthermore, confirmed by some empirical correlations. The analysis
      of the average hysteresis on adsorption-desorption isotherms as well as the
      comparison of phenol adsorption in oxic and anoxic conditions leads to the
      mechanism of irreversible phenol adsorption. It is suggested that the
      irreversibility is caused by two effects: the creation of strong complexes
      between phenol and surface carbonyl and lactones as well as by the
      polymerization. The last effect is due to the ability of carbon to adsorb the
      oxygen from solution and form superoxo ions. Finally, the kinetics is considered.
      The analytical solution of Fick's law of diffusion for adsorption in cylindrical
      particles is applied, the diffusion coefficients are calculated. It is shown that
      phenol diffusion is mixed between a surface process and a pore one. The obtained
      energy of diffusion is correlated with the values of the physicochemical
      parameters of studied carbons. As a final point, it is concluded that the
      mechanism of phenol adsorption is not only determined by so called "pi-pi
      interactions" and "donor-acceptor complex formation" but also by (strongly
      depending on temperature) the "solvent effect" balancing the influence of the two
      mentioned factors on this mechanism.

PMID- 14643232
TI  - Skim and cream natural rubber particles: colloidal properties, coalescence and
      film formation.
AB  - Cream and skim fractions of freshly tapped natural rubber latex have been studied
      using atomic force microscopy and scanning electric potential microscopy to
      elucidate the topology and charge properties in film formation. Elemental
      distribution maps of the particles have also been obtained using electron energy
      loss imaging in a low-energy transmission electron microscope. The two rubber
      fractions are obtained by centrifugation. The cream fraction is stable while
      rapid coagulation occurs in the skim fraction. After removal of the coagulum, no
      further coagulation occurs and the remaining skim rubber particles are stable.
      The rubber particles from the cream rubber particles contain higher amount of
      adsorbed protein-phospholipid materials compared to those in the "self-cleaned"
      skim fraction. This difference in membrane property has a significant impact on
      the spreading of the cis-1,4-polyisoprene cores, their coalescence and film
      formation behavior. Coalescence of cream particles appears to be hindered by the
      membrane materials, forming a rough film that retains the topology of individual
      particles. Skim particles coalesce more readily, forming relatively smooth films.

PMID- 14643233
TI  - Influence of surface and bulk structures of acrylic PSA films onto their tack
      properties.
AB  - PSA films are obtained by coalescence of latices synthesized by free-radical
      emulsion polymerization of methyl methacrylate (MMA) and 2-ethylhexyl acrylate
      (EHA). For the same overall 50/50 molar composition, the polymer particles have
      well-defined structures when the feed composition and the feed mode (using batch
      or semicontinuous processes) are adjusted. The characterizations of the film
      structures by surface (tapping mode AFM) and bulk (DSC, rheology) analyses argue
      for the conservation of the initial particle structure when coalescence occurs.
      The influence of the chemical heterogeneity on the tack properties of the films
      is investigated to extend the study of these original acrylic PSA films up to
      relevant structure-property correlations.

PMID- 14643234
TI  - Structure and catalytic properties of nanosized alumina supported platinum and
      palladium particles synthesized by reaction in microemulsion.
AB  - Mixtures of nanosized platinum and palladium particles have been prepared by
      reduction of salt-containing microemulsion droplets using hydrazine as the
      reducing agent. To avoid possible negative effects of the presence of sulfur
      compounds during the preparation the microemulsion was made using the sulfur-free
      nonionic polyoxyethylene 4 lauryl ether surfactant. Transmission electron
      microscopy showed that the as-prepared mixtures contained crystalline platinum
      particles of fairly homogeneous size (20 to 40 nm) with adsorbed amorphous
      palladium particles 2 to 5 nm in size. Catalyst samples were prepared by
      depositing the nanoparticles on a gamma-Al(2)O(3) support followed by heating in
      air at 600 degrees C. Alloyed particles of platinum and palladium with sizes
      ranging from 5 to 80 nm were obtained during the heating. The majority of the
      particles had the fcc structure and their compositional range was dependent upon
      the Pt:Pd molar ratio of the microemulsion. A catalyst prepared from a
      microemulsion with a 20:80 Pt:Pd molar ratio showed the highest catalytic
      activity for CO oxidation, while pure platinum and palladium catalysts showed
      higher sulfur resistance. These results differ from the performance of
      conventional wet-impregnated catalysts, where a 50:50 Pt:Pd molar ratio resulted
      in the highest catalytic activity as well as the highest sulfur resistance.

PMID- 14643235
TI  - Controlling synthesis of silver nanowires and dendrites in mixed surfactant
      solutions.
AB  - Using a simple wet chemical route, high-yield silver nanowires with an average
      diameter of 25+/-5 nm and length up to several microm and dendrites with a long
      central backbone and symmetrically ramified secondary branches have been
      successfully obtained by reducing AgNO(3) with L-ascorbic acid (AsA) in the mixed
      surfactant solutions of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl
      sulfate (SDS). It was found that the architecture of silver nanocrystals was
      drastically influenced by the concentrations of ascorbic acid. At a given high
      concentration, a nonequilibrium system was easily built, which favored the
      formation of fractals. When the concentration was lowered, one-dimensional silver
      nanowires were successfully obtained. In addition, the presence of electrolyte
      (NaCl) plays an important role in the preparation of silver nanowires,
      influencing the silver crystallization process in surprising ways.

PMID- 14643236
TI  - Strain fields at contacts between small particles.
AB  - Stress fields between interacting small particles ( approximately 100 nm) have
      been investigated by transmission electron microscopy. The background for these
      TEM observations is discussed in terms of adhesion stress fields (due to surface
      forces), the action of an applied point force, possibly magnetic, and
      dislocations or misfit strains due to an unfavorable matching of crystal lattices
      at the grain boundary. A further explanation might be sought along the line
      "squeezed-in oxide" which can be visualized as a coherent particle or a
      dislocation loop. Accompanying theoretical calculations have been performed and
      compared with the experimental results.

PMID- 14643237
TI  - Suspended particles surrounded by an inhomogeneously charged permeable membrane.
      Solution of the Poisson-Boltzmann equation by means of the network method.
AB  - The Poisson-Boltzmann equation is numerically solved for a suspended spherical
      particle surrounded by a permeable membrane that contains an inhomogeneous
      distribution of fixed charges. The calculations are carried out using the network
      simulation method, which makes it possible to solve the problem in the most
      general case, extending previous results (J.P. Hsu, Y.C. Kuo, J. Membrane Sci.
      108 (1995) 107). Approximate analytical expressions for the counterion
      concentration and the electric potential in the membrane are also presented,
      together with criteria that determine their ranges of validity. The limiting case
      of a distribution of fixed charges in the membrane that reduces to a surface
      charge is also analyzed. It is shown that the solution for this case, considering
      a vanishingly small radius of the core, reduces to a superposition of solutions
      corresponding to a charged impermeable particle suspended in an electrolyte
      solution and to a cavity filled with a charged electrolyte solution.

PMID- 14643238
TI  - Heteroflocculation of binary latex dispersions of similar chemistry but varying
      size.
AB  - The stability of dilute bimodal (diameter:100 and 200 nm) model latex dispersions
      is studied as a function of electrolyte concentration and particle number
      fraction by measuring perikinetic aggregation with dynamic light scattering. A
      formally correct expression for the effective, doublet stability ratio of a
      bimodal system is derived that accounts for the difference in the particle size
      and hence, extends the derivation by Hogg and co-workers [Trans. Faraday Soc. 62
      (1966) 1638]. Including the particle size ratio predicts slightly lower stability
      ratios for polydisperse but chemically similar systems. Stability ratios for
      binary mixtures of model colloidal latices are extracted from aggregation
      measurements in the fractal aggregation regime and are compared to predictions
      based on DLVO calculations of the potential. The results suggest that the
      composition of the aggregates is dependent on the relative stability of the two
      components (and consequently, on electrolyte concentration) and is richer in the
      least stable component.

PMID- 14643239
TI  - Dithiol-mediated incorporation of CdS nanoparticles from reverse micellar system
      into Zn-doped SBA-15 mesoporous silica and their photocatalytic properties.
AB  - CdS nanoparticles, as prepared in reverse micellar systems, were incorporated
      into alkanedithiol-modified Zn-doped SBA-15 mesoporous silica (dtz.sbnd;ZnSBA-15;
      pore diameter, ca. 4 nm), which were themselves prepared via hydrolysis of
      tetraethylorthosilicate (TEOS) in the presence of Zn(NO(3))(2) and triblock
      copolymer, as a nonsurfactant template and pore-forming agent, followed by
      contact with dithiol molecules. A particle-sieving effect for the dtz.sbnd;ZnSBA
      15 was observed, in that the incorporation of the nanoparticles was remarkably
      decreased with increasing the nanoparticle size. The resulting CdSz.sbnd;ZnSBA-15
      composite was then used as photocatalysts for the generation of H(2) from 2
      propanol aqueous solution. Under UV irradiation (lambda>300 nm), a high
      photocatalytic activity was observed for this composite material. This is
      effected by electron transfer from the photoexcited ZnS (dithiol-bonded Zn on SBA
      15) to CdS nanoparticles. The photocatalytic activity is increased with a
      decrease in the number of methylene groups in the dithiol molecules, according to
      the rank order 1,10-decanedithiol < 1,6-hexanedithiol < 1,2-ethanedithiol.

PMID- 14643240
TI  - Stern-layer parameters of alumina suspensions.
AB  - The specific adsorption of Mg(+2) and S(2)O(-2)(8) ions onto the gamma-alumina
      particle surface has been demonstrated. An estimation algorithm based upon the
      correlation between electrophoretic mobility and conductivity increment
      experimental data, employing a dynamic Stern-layer theory, has been developed and
      used to get the adsorption parameters into the Stern layer for different gamma
      alumina/Mg(+2) and S(2)O(-2)(8) aqueous solutions interface.

PMID- 14643241
TI  - Treatment of radioactive wastes: an X-ray absorption spectroscopy study of the
      reaction of technetium with green rust.
AB  - Technetium is a long-lived product of nuclear fission that readily forms the
      soluble pertechnetate anion [TcO(4)](-). Green rusts (layered hydrous oxides
      containing both Fe(II) and Fe(III) and with interlayer sulfate or carbonate
      anions) concentrate >99.8% of 99Tc, present as [TcO(4)](-), from aqueous
      solution, even in the presence of high concentrations of NaNO(3), a common
      constituent of radioactive waste streams. The mechanism of removal from solution
      is apparently reduction and formation of strong Tc(IV) surface complexes. X-ray
      absorption spectroscopy shows that [TcO(4)](-) is indeed reduced by reaction with
      both sulfate- and carbonate-form green rusts and is found in a TcO(2)-like
      environment. On contact with air, the green rusts oxidize to poorly crystalline
      goethite but the Tc environment is unchanged. There is no increase in Tc
      solubility associated with oxidation of the host green rust. This behavior
      suggests that green rusts may be useful in the treatment of Tc-containing waste
      streams, in groundwater cleanup, and in restricting Tc migration from
      repositories.

PMID- 14643242
TI  - Diffuse reflectance FT-IR spectroscopic study of interactions of alpha
      Al2O3/molten alkali nitrate coexisting systems.
AB  - The diffuse reflectance spectra of alpha-Al(2)O(3)/molten MNO(3) (M=K(+), Li(+))
      coexisting systems have been measured for the investigation of the
      physicochemical properties of molten nitrate at the interface of aluminum oxide.
      In the region of overtone and combination modes from 3000 to 1700 cm(-1), the
      absorption band nu(3)+nu(4) decreases with increasing specific surface area of
      alpha-Al(2)O(3) powder for the potassium mixtures. Gaussian resolution of
      nu(3)+nu(4) also exhibits changes in band positions of components with the
      variation in the alumina specific surface area and the nitrate melt content. The
      second-order derivative of the spectra in the region from 1700 to 950 cm(-1)
      shows a set of peaks at 1645, 1554-1516, and 1452 cm(-1) characteristic of a
      coordinated nitrate ion. The peak at 1337 cm(-1) suggests a possible formation of
      nitrite species. The maxima of nu(3)+nu(4), nu(1)+nu(2), and nu(1)+nu(4) shift
      toward lower frequencies with increasing temperature above the nitrate melting
      point. This information shows that the intramolecular bonds of NO(3)(-) are
      affected. These perturbations are attributed to the effect of the solid phase
      interacting with the liquid phase. The interaction between solid and liquid
      phases affects the geometry of the ionic species and, therefore, influences the
      electrical properties of nitrate ions.

PMID- 14643243
TI  - Effect of sodium dodecyl sulfate on the rate of hydrogen evolution at a cathode.
AB  - The effect of H(2) evolution on the mass-transfer coefficient of cathode
      reduction of potassium ferricyanide at a mercury cathode was studied with the aim
      of (i) comparing the mass transfer behavior at a Hg cathode with that at solid
      electrodes under gas-evolving conditions and (ii) testing the effect of anionic
      surface-active agent on the mass transfer behavior of an H(2)-evolving Hg
      cathode. It is found that the mass transfer coefficient at the Hg cathode was
      much higher than the value at a solid cathode. The mass transfer coefficient at
      H(2)-evolving Hg was found to decrease in the presence of sodium dodecyl sulfate
      (SDS) surfactant by an amount ranging from 58.8 to 76%, depending on the H(2)
      discharge rate and the SDS concentrations.

PMID- 14643244
TI  - Potential distribution around a polyelectrolyte-coated spherical particle in a
      salt-free medium.
AB  - Simple analytic approximate expressions for the solution to the Poisson-Boltzmann
      equation around a spherical particle coated with an ion-penetrable
      polyelectrolyte layer in a salt-free medium containing counterions only are
      derived. The results of the calculation of the potential distribution using the
      approximate solution are found to be in good agreement with exact numerical
      results. It is shown that as in the case of a charged rigid particle, there is a
      certain critical value of the particle charge, separating two cases, that is, the
      low-particle-charge case and the high-particle-charge case. In the low-charge
      case the potential is essentially the same as if counterions were absent and thus
      the potential is proportional to the particle charge. In the high-charge case
      counterion condensation occurs in the polyelectrolyte layer region, so that the
      dependence of the potential on the particle charge is considerably suppressed.

PMID- 14643245
TI  - Characterization of silica-pillared derivatives from aluminum-containing
      kanemite.
AB  - A series of aluminum-containing kanemite (Al-kanemite) samples with several Si/Al
      molar ratios were synthesized. The Al-kanemite samples were pillared with silica.
      X-ray diffractograms showed that the layered structure of the Al-kanemite samples
      was maintained at Si/Al= infinity approximately 10 but was broken at Si/Al = 5,
      2.5, and 1. 29Si MAS NMR spectra of the Al-kanemite samples, except for that of
      Si/Al = 1, mainly showed peaks of Q(3) sites, which were attributed to
      Si(OSi)(3)(OH) groups, although peaks assigned to Si(OAl)(OSi)(2)(OH) were also
      seen. The 27Al MAS NMR spectra indicated that the Al-kanemite samples had only
      four-coordinate aluminum atoms. The FTIR spectra of pyridine adsorbed on the
      pillared Al-kanemite derivatives revealed Lewis acid sites on the surface. The
      nitrogen adsorption isotherms of the derivatives were classified as type I
      (Langmuir) absorption isotherms. Using the alpha(s) method, the specific surface
      areas of the derivatives were 572-756 m(2)g(-1), and the pore sizes were
      calculated as 1.25-1.83 nm. The pillared Al-kanemite derivatives had slit-shaped
      micropore structures.

PMID- 14643246
TI  - Physicochemical evaluation of PLA nanoparticles stabilized by water-soluble MPEO
      PLA block copolymers.
AB  - Different water-soluble MPEO-PLA diblock copolymers with various alpha-methoxy
      omega-hydroxyl polyethylene (MPEO) and poly(lactic acid) (PLA) block lengths have
      been synthesized. Their surface-active properties were evidenced by surface
      tension (water/air) measurements. In each case the surface tension leveled down
      above a critical polymer concentration, which was attributed to the formation of
      a dense polymer layer at the liquid-air interface. The applicability of
      copolymers as emulsion stabilizers in the preparation of PLA nanospheres by an
      o/w emulsion/evaporation technique was then investigated. Four copolymers
      presenting sufficient water solubility and good surfactive properties were used
      to prepare PLA nanospheres with MPEO chains firmly anchored at the particle
      surface. The effect of polymer concentration in emulsion on particle size and
      surface coverage was examined. Whatever the copolymer characteristics, it was
      found that the optimal concentration to obtain a large amount of MPEO at the
      particle surface was similar (around 2 g/l). The effect of the copolymer
      composition on MPEO layer characteristics and on colloidal stability was also
      evaluated. The conformation of MPEO blocks at the PLA particle surface is
      discussed in relation to the layer thickness and the surface area occupied per
      molecule.

PMID- 14643247
TI  - Pattern formation in thin liquid films with charged surfactants.
AB  - The dynamic evolution of positively charged surfactants at the interface of a
      thin film resting atop a negatively charged base is investigated. The lubrication
      approximation is used to develop coupled equations governing the dynamic
      evolution of such a system in the presence of charge effects coupled with van der
      Waals forces. The equations are investigated numerically and analytically, and,
      for certain parameter ranges, pattern formation is observed reminiscent of that
      accompanying thermocapillary-driven thin films. Spatial nonuniformities in the
      charge of the underlying substrate are also studied as a possible tool for film
      rupture wavelength selection.

PMID- 14643248
TI  - Interaction of elastic bodies via surface forces. 2. Exponential decay.
AB  - Our goal is to study theoretically the effect of deformation on the exponentially
      decaying interaction of two elastic solids separated by a thin liquid film. The
      deformed shape of the surfaces and the contribution of the elasticity to the
      total force, i.e., an additional term present between elastic bodies, are
      calculated from continuum elastic theory via a new asymptotic technique. Both the
      deformation and the contribution of the elasticity to the force are found to be
      significant on the length scale over which the surface force acts. The surface
      deformation is exponentially decaying with a decay length equal to that of the
      original surface interaction. It is especially important for large and/or rapidly
      changing force. The contribution of the elasticity is also exponentially
      decaying, but with half the decay length. Its strength depends on the elastic
      constants and size of the solids and on the magnitude and gradient of the
      original surface force. Depending on how the separation is detected, it can
      appear either as an attractive or as a repulsive contribution to the force. Our
      results open the possibility of recalculating the measured force to the
      interaction free energy.

PMID- 14643249
TI  - Permeation of electrolyte water-methanol solutions through a Nafion membrane.
AB  - The volume flux through a cation-exchange membrane (Nafion 117) separating two
      equal electrolyte water-methanol solutions as a function of the pressure
      difference was determined under different experimental conditions. The results
      show that permeation rates through the membrane are strongly dependent on the
      methanol content of the solutions, thus the value of the flux increases when the
      methanol percentage increases. The effect of the electrolyte concentration of the
      solution on the membrane permeability is less important, although its influence
      becomes significant at low electrolyte concentration and high methanol content on
      solvent. This behavior is explained in terms of the amount of solvent sorbed by
      the membrane. Typical flux behaviors observed with pressure difference are linear
      at low pressures, exhibiting a positive deviation at higher pressure difference
      values.

PMID- 14643250
TI  - Studies of mixed surfactant solutions of cationic dimeric (gemini) surfactant
      with nonionic surfactant C12E6 in aqueous medium.
AB  - The interaction between the alkanediyl-alpha,omega-type cationic gemini
      surfactant, [(C(16)H(33)N(+)(CH(3))(2)(CH(2))(4)N(+)(CH(3))(2)C(16)H(33))2Br(-)],
      16-4-16 and the conventional nonionic surfactant
      [CH(3)(CH(2))(10)CH(2)(OCH(2)CH(2))(6)OH], C(12)E(6) in aqueous medium has been
      investigated. The critical micelle concentrations of different mixtures have been
      measured by surface tension using a du Nouy tensiometer in aqueous solution at
      different temperatures (303, 308, and 313 K). Maximum surface excess (Gamma(max))
      and minimum area per molecule (A(min)) were evaluated from a surface tension vs
      log(10)C (C is concentration) plot. The cmc value of the mixture was used to
      compute beta(m), the interaction parameter. The beta(sigma), the interaction
      parameter at the monolayer air-water interface, was also calculated. We observed
      synergism in 16-4-16/C(12)E(6) system at all concentration ratios. The micelle
      aggregation number (N(agg)) has been measured using a steady state fluorescence
      quenching method at a total surfactant concentration approximately 2 mM at 25
      degrees C. The micropolarity and the binding constant (K(sv)) of mixed systems
      were determined from the ratio of intensity of peaks (I(1)/I(3)) of the pyrene
      fluorescence emission spectrum. The micellar interiors were found to be
      reasonably polar. We also found, using Maeda's concept, that the chain-chain
      interactions are very important in this system.

PMID- 14643251
TI  - Phase transport of HCl, HFeCl4, water, and crude oil components in acid-crude oil
      systems.
AB  - A model describing the transport of HCl and HFeCl(4) from a water phase to a
      crude oil phase and subsequent sludge formation is proposed. Crude oil phase
      transfer compounds (PTCs) that are basic in nature facilitate transport of acid
      to the crude oil phase. These crude oil PTCs are able to migrate to the acid-oil
      interface and form acid-base complexes that can return to the oil phase. Once in
      the crude phase, these protonated compounds have a propensity to form aggregates.
      Growth of small aggregates into larger aggregates eventually generates a
      precipitate known as acid-sludge. Under certain conditions the model predicts the
      amount of acid-sludge formed to be proportional to the acid activity, or acidity
      function H(0), in the water phase. This relation was confirmed experimentally.
      Furthermore, the total amount of phase-transported acid is proportional to the
      base content of the crude oil. In strong HCl formulations containing Fe(3+), the
      acid HFeCl(4) is formed in small amounts that can be transported to the crude oil
      phase. In principle, the behavior of HFeCl(4) is similar to that of HCl. It was
      shown that HCl and HFeCl(4) compete for basic, or receptor, sites and that
      exchange between these two acids is reversible. The antisludging agent
      dodecylbenzenesulfonic acid, DBSA, intervenes through the same mechanism; that
      is, it competes for receptor sites with HCl and HFeCl(4). Exchange between
      HCl/HFeCl(4) and DBSA was also shown to be reversible.

PMID- 14643252
TI  - Morphological change of gold-dendrimer nanocomposites by laser irradiation.
AB  - Gold-dendrimer nanocomposites are prepared in aqueous solutions in the presence
      of poly(amidoamine)dendrimers (PAMAM) (generation 3 and 5) or
      poly(propyleneimine)dendrimers (PPI) (generation 3 and 4) by wet chemical NaBH(4)
      method. Thus prepared gold-dendrimer nanocomposites are irradiated by laser at
      532 nm. UV-vis absorption spectroscopy and transmission electron microscopy
      reveal that the gold nanoparticles grow with the laser irradiation time as well
      as the fluence of the laser; in particular, the gold nanoparticles prepared at
      lower concentrations of PAMAM dendrimer as well as lower generations of PAMAM
      grow significantly. On the other hand, in the case of PPI dendrimers, the gold
      nanoparticles hardly grow by irradiation. In addition, dynamic light-scattering
      measurements show that the laser irradiation markedly promotes the association of
      the gold-PAMAM G3 dendrimer nanocomposites compared to that of the gold-PAMAM G5
      dendrimer nanocomposites, while the sizes of association for the gold-PPI G3, G4
      dendrimer nanocomposites hardly change by laser irradiation.

PMID- 14643254
TI  - Quantification of substratum contact required for initiation of Colletotrichum
      graminicola appressoria.
AB  - Colletotrichum graminicola, like many plant pathogenic fungi develop appressoria
      on germling apices, to facilitate penetration of their host. Induction of these
      structures occurs after contact with the host surface has been established by the
      germling. Surface contact and subsequent development of appressoria by germlings
      of C. graminicola was assessed using interference-reflection microscopy (IRM) and
      microfabricated pillared silicon substrata. Observations with IRM revealed that
      under low nutrient conditions, 90% of the germlings developed appressoria once
      they established 4.5 microm of continuous contact with the substratum. Substrata
      bearing pillars < or =5 microm in width supported < or =10% appressoria; however,
      as pillar width was increased the percentage of appressoria formed increased in a
      sigmoid fashion to a maximum of 80%. The percentage of appressoria produced
      experimentally on these surfaces was compared to data sets generated from a model
      designed to calculate the probability of appressorium development on similar
      pillar arrays at various germ tube contact lengths. These results indicate that
      germ tubes of C. graminicola require more than 4microm of continuous contact with
      a hydrophobic substratum for induction of appressoria.

PMID- 14643255
TI  - Aspergillus nidulans RhoA is involved in polar growth, branching, and cell wall
      synthesis.
AB  - Growth of the filamentous fungus Aspergillus nidulans begins when the conidium
      breaks dormancy and grows isotropically. Eventually a germ tube emerges and the
      axis of growth remains fixed in the primary hypha while new growth axes are
      established basally to form secondary germ tubes and lateral branches. Rho1 is a
      Rho family GTPase that has been shown to be involved in polarity establishment
      and cell wall deposition in Saccharomyces cerevisiae. A gene predicted to encode
      a Rho1 homolog was cloned from A. nidulans and named rhoA. Strains carrying
      ectopic copies of the constitutively active rhoA(G14V) allele or the dominant
      rhoA(E40I) allele were created and characterized. The constitutively active
      rhoA(G14V) strain grew slowly relative to wild type and showed an abnormal
      clustered pattern of branch emergence. The rhoA(G14V) strain also labeled
      intensely with calcofluor, showed elevated levels of cell wall N
      acetylglucosamine and had unusually thick cell walls. The dominant
      rhoA(E40I)strain was accelerated in the emergence of secondary and tertiary germ
      tubes, and lateral branches relative to wild type and showed lysis with prolonged
      incubation. The rhoA(E40I) strain also was hypersensitive to the cell wall
      disrupting agents calcofluor and caspofungin acetate and showed an increase in
      cell wall N-acetylglucosamine levels. Our results suggest that rhoA plays a role
      in polarity, proper branching pattern, and cell wall deposition.

PMID- 14643256
TI  - Contig assembly and microsynteny analysis using a bacterial artificial chromosome
      library for Epichloe festucae, a mutualistic fungal endophyte of grasses.
AB  - We constructed and characterized a bacterial artificial chromosome (BAC) library
      for Epichloe festucae, a genetically tractable fungal plant mutualist. The 6144
      clone library with an average insert size of 87kb represents at least 18-fold
      coverage of the 29 Mb genome. We used the library to assemble a 110kb contig
      spanning the putative ornithine decarboxylase (odc) ortholog and subsequently
      expanded it to 228kb with a single walking step in each direction. Furthermore,
      we evaluated conservation of microsynteny between E. festucae and some model
      filamentous fungi by comparing sequence available from a 43kb region at the end
      of one BAC to publicly available fungal genome sequences. Orthologs to the 13
      contiguous open reading frames (ORFs) identified in E. festucae are syntenic in
      Neurospora crassa and Magnaporthe grisea occurring in small sets of two, three or
      four colinear ORFs. This library is a valuable resource for research into traits
      important for the development and maintenance of a plant-fungus mutualistic
      symbiosis.

PMID- 14643257
TI  - Isolation and disruption of the melanin pathway polyketide synthase gene of the
      softwood deep stain fungus Ceratocystis resinifera.
AB  - Ceratocystis resinifera hyphae produce a black melanin pigment causing a deep
      stain in softwood logs. We exploited the homology of polyketide synthases to
      clone PKS1, a gene responsible for dihydroxynaphthalene-melanin biosynthesis in
      C. resinifera. Sequence analysis indicated that PKS1 has two introns near its
      5(') end and encodes a 2188-amino acid polypeptide with five functional domains:
      beta-ketoacyl synthase, acyl transferase, two acyl carrier proteins and a
      thioesterase/Claisen cyclase. A gene disruption construct designed to replace a
      portion of PKS1 with a hygromycin resistance cassette was transformed into C.
      resinifera through Agrobacterium tumefaciens-mediated transformation. PKS1 null
      mutants had an albino phenotype, and pigmentation was restored by the addition of
      scytalone, a melanin pathway intermediate. The disruption of PKS1 and restoration
      of pigmentation with scytalone confirmed the presence of a dihydroxynaphthalene
      melanin pathway in C. resinifera. The transformation method described in this
      paper is the first reported for a Ceratocystis species.

PMID- 14643258
TI  - Ammonium-induced internalisation of UapC, the general purine permease from
      Aspergillus nidulans.
AB  - The Aspergillus nidulans UapC protein is a high-affinity, moderate-capacity, uric
      acid-xanthine transporter, which also displays a low transport capacity for
      hypoxanthine, adenine, and guanine. It has been previously shown that a
      functional UapC-GFP fusion protein localises at the plasma membrane. Here, we
      demonstrate that ammonium, a preferred nitrogen source, dramatically changes the
      subcellular distribution of UapC. After addition of ammonium, UapC-GFP is removed
      from the plasma membrane and is concentrated into the vacuolar compartment. A
      chimeric gene construct in which an inducible promoter, insensitive to nitrogen
      repression, drives the expression of UapC-GFP, allowed us to demonstrate that the
      ammonium-dependent redistribution of UapC can be dissociated from the
      transcriptional repression of the gene. These results provide further support for
      the occurrence of endocytosis and the lysosomal-endosomal function of the
      vacuolar compartment in A. nidulans.

PMID- 14643259
TI  - Guest, a transposable element belonging to the Tc1/mariner superfamily is an
      ancient invader of Neurospora genomes.
AB  - Guest is a transposable element of the Tc1/mariner superfamily with 30-40bp
      terminal inverted repeats and a TA dinucleotide target site duplication. Guest
      was originally discovered in the St. Lawrence 74A laboratory strain of the
      filamentous fungus Neurospora crassa. In this report, Guest iterations subcloned
      from a cosmid library of the Oakridge 74A strain were used to design PCR primers
      that permitted the detection of Guest in wild isolates of N. crassa. Guest is
      present in N. crassa as multiple copies ranging between 100bp and 2.4kb and is
      present in the mating type locus of several Neurospora species. Bioinformatic
      analysis of the entire N. crassa genome (Oakridge 74A strain) detected 48 Guest
      iterations. All iterations appeared to have been inactivated either by repeat
      induced point mutation or sequence deletion, with the majority being remnants
      less than 400bp in length. The possible involvement of Guest in the evolution of
      the variable region that flanks the mating type idiomorphs in several Neurospora
      species is discussed.

PMID- 14643260
TI  - Phytophthora sojae avirulence genes Avr4 and Avr6 are located in a 24kb,
      recombination-rich region of genomic DNA.
AB  - A cross between two different races (race 7xrace 25) of the soybean root and stem
      rot pathogen Phytophthora sojae was analyzed to characterize the genomic region
      flanking two cosegregating avirulence genes, Avr4 and Avr6. Both genes
      cosegregated in the ratio of 82:17 (avirulent:virulent) in an F(2) population,
      suggestive of a single locus controlling both phenotypes. A chromosome walk was
      commenced from RAPD marker OPE7.1C, 2.0cM distant from the Avr4/6 locus. Three
      overlapping cosmids were isolated which included genetic markers that flank the
      Avr4/6 locus. The chromosome walk spanned a physical distance of 67kb which
      represented a genetic map distance of 22.3cM, an average recombination frequency
      of 3.0kb/cM and 11.7-fold greater than the predicted average recombination
      frequency of 35.3kb/cM for the entire P. sojae genome. Six genes (cDNA clones)
      expressed from the Avr4/6 genomic region encompassed by the cosmid contig were
      identified. Single nucleotide polymorphisms and restriction fragment length
      polymorphisms showed these six genes were closely linked to the Avr4/6 locus.
      Physical mapping of the cDNA clones within the cosmid contig made it possible to
      deduce the precise linkage order of the cDNAs. None of the six cDNA clones appear
      to be candidates for Avr4/6. We conclude that two of these cDNA clones flank a
      physical region of approximately 24kb and 4.3cM that appears to include the
      Avr4/6 locus.

PMID- 14643261
TI  - Aspergillus nidulans hypA regulates morphogenesis through the secretion pathway.
AB  - Aspergillus nidulans hypA encodes a predicted 1474 amino acid, 161.9 kDa
      cytoplasmic peptide. Strains with hypA1 and hypA6 alleles are wild type at 28
      degrees C but have wide, slow-growing hyphae and thick walls at 42 degrees C.
      hypA1 and hypA6 have identical genetic lesions. hypA1 and hypA6 restrictive
      phenotypes have statistically similar morphometry, and strains with either allele
      can conidiate at 42 degrees C. hypA deletion strains require osmotic support and
      have aberrant morphology, but produce viable spores at 28 degrees C. hypA has
      full-length orthologs in filamentous fungi and yeasts and a 200 amino acid region
      with similarity to sequences in plants and animals. The Saccharomyces cerevisiae
      hypA ortholog is TRS120, a regulatory subunit in the TRAPP II complex that
      mediates traffic through the Golgi equivalent. Enzyme secretion is reduced in
      hypA1 cells at 42 degrees C. Endomembranes and cytoplasmic actin arrays in hypA1
      have weak polarity at 42 degrees C and cytoplasmic microtubules have reduced
      number and normal distribution.

PMID- 14643262
TI  - Crossing the boundary between the Balpha and Bbeta mating-type loci in
      Schizophyllum commune.
AB  - In this study, genes of the Schizophyllum commune Balpha and Bbeta mating-type
      loci are shown to be within a few kilobases of each other. The region between the
      nearest Balpha and Bbeta genes contains many short direct repeats. Predicted
      amino acid sequences and activity spectra of three pheromones encoded in the
      Balpha3 mating-type specificity are presented along with a re-evaluation of
      pheromone activity of many previously reported S. commune lipopeptide pheromones.
      This analysis showed that S. commune pheromones belong to five subtypes. Several
      pheromones activate both a Bbeta receptor and a Balpha receptor, a phenomenon
      previously unrecognized. Clues from mating tests and DNA hybridization led to the
      cloning of bar8, the gene encoding the Balpha8 pheromone receptor, Bar8. Bar8 is
      similar in sequence to Bbr1, the Bbeta1 pheromone receptor, and functionally
      identical to it. These data begin to elucidate the enigmatic recombination
      patterns previously encountered at the B mating-type complex.

PMID- 14643263
TI  - Dicarboximide resistance in field isolates of Alternaria alternata is mediated by
      a mutation in a two-component histidine kinase gene.
AB  - Isolates of Alternaria alternata collected from a field site which had previously
      been treated with the dicarboximide fungicide iprodione were found to demonstrate
      a high level of resistance to iprodione and the phenylpyrrole fungicide,
      fludioxonil in plate assays. In order to determine the genetic basis for this
      fungicide resistance a partial length clone of a two-component histidine kinase
      (HK) was isolated from genomic DNA of a fungicide-sensitive A. alternata isolate
      using degenerate primers by PCR. Analysis of the AaHK1 gene structure indicates
      the presence of six 90 amino acid repeat domains upstream of a kinase domain as
      found in the homologous HK genes from other fungal species. Comparison of nucleic
      acid sequences from the fungicide-sensitive and fungicide-resistant A. alternata
      isolates confirmed the presence of mutations leading to premature termination of
      the translated HK protein. The possible role of the two-component HK in the
      development of dicarboximide resistance in A. alternata is discussed.

PMID- 14643264
TI  - 'The patient takes charge'--long term use of the atrial defibrillator.

PMID- 14643265
TI  - A paradigm shift in treatment for atrial fibrillation: from electrical to
      structural therapy?

PMID- 14643266
TI  - Does periodontitis cause heart disease?

PMID- 14643267
TI  - Microvessel haemodynamics: interesting news which is not NO news?

PMID- 14643268
TI  - Treatment of atrial fibrillation with an implantable atrial defibrillator--long
      term results.
AB  - OBJECTIVES: To evaluate the long-term outcome with an implantable atrial
      defibrillator (IAD) in patients with recurrent atrial fibrillation (AF).
      BACKGROUND: Maintenance of sinus rhythm using repeated internal cardioversion
      shocks has been shown to be effective and safe in short-term studies but long
      term follow-up is unknown. METHODS: Since 1995, 136 patients (30 women) with
      symptomatic, drug-refractory atrial fibrillation were implanted with an IAD
      (METRIX, InControl). This analysis was performed after a median of 40 (range 7
      66) months after implantation. RESULTS: In 26 patients, the programmed mode was
      not documented during last follow-up, four patients had died. Of the remaining
      106 patients (mean age 58+/-10, range 34 - 79 years), 39 were actively delivering
      therapy with the device, in 14 patients the device was used to monitor the
      arrhythmia but no shocks were delivered, and in 53 patients it was turned off or
      explanted. Increases in defibrillation thresholds (n=7), patient intolerance of
      multiple cardioversion shocks (n=15), and significant bradycardia requiring dual
      chamber pacing (n=12) were the main reasons for discontinuation of therapy in
      addition to battery depletion (n=19). After explantation, efforts to maintain
      sinus rhythm were continued in 17 patients whereas rate control was attempted in
      36 patients. CONCLUSIONS: A strategy of maintaining sinus rhythm long-term with
      an IAD is feasible in a proportion of patients. However, patient selection is
      critical, and technical improvements (i.e. higher shock energies, dual-chamber
      pacing and additional preventive and anti-tachycardia pacing algorithms) are
      required to increase the number of patients having long term benefit, and
      frequent arrhythmia recurrences and patient intolerance to repeated cardioversion
      shocks remain a major limitation.

PMID- 14643269
TI  - Use of enalapril to facilitate sinus rhythm maintenance after external
      cardioversion of long-standing persistent atrial fibrillation. Results of a
      prospective and controlled study.
AB  - AIMS: This study aimed to assess whether enalapril could improve cardioversion
      outcome and facilitate sinus rhythm maintenance after conversion of chronic
      atrial fibrillation (AF). METHODS AND RESULTS: Patients with chronic AF for more
      than 3 months were assigned to receive either amiodarone (200mg orally 3 times a
      day; group I: n=75) or the same dosage of amiodarone plus enalapril (10mg twice a
      day; group II: n=70) 4 weeks before scheduled external cardioversion. The end
      point was the time to first recurrence of AF. In 125 patients (86.2%), AF was
      converted to sinus rhythm. Group II had a trend to a trend to a lower rate of
      immediate recurrence of AF than group I did (4.3% vs 14.7%, P=0.067). Kaplan
      Meier analysis demonstrated a higher probability of group II remaining in sinus
      rhythm at 4 weeks (84.3% vs 61.3%, P=0.002) and at the median follow-up period of
      270 days (74.3% vs 57.3%, P=0.021) than in group II. CONCLUSIONS: The addition of
      enalapril to amiodarone decreased the rate of immediate and subacute arrhythmia
      recurrences and facilitated subsequent long-term maintenance of sinus rhythm
      after cardioversion of persistent AF.

PMID- 14643270
TI  - Risk factors for cardiovascular disease in patients with periodontitis.
AB  - AIMS: This study compared plasma levels of established risk markers for
      atherosclerosis and indices of inflammation in 50 patients with severe
      periodontitis to those in 46 healthy cases. METHODS AND RESULTS: Full blood
      counts were performed and levels of high density lipoproteins (HDL), total
      cholesterol, haptoglobin, elastase, C-reactive protein (CRP), IL-6, TNFalpha
      receptor-1, alpha-1-antitrypsin and antibodies against human heat shock protein
      (Hsp) 60, mycobacterial Hsp65 and oxLDL were determined. Total cholesterol levels
      were similar in both groups, whereas HDL levels were lower (P=0.007) and the
      lipid profile (total cholesterol/HDL) was consequentially higher (P=0.03) in
      patients. Monocyte counts were elevated (0.56 vs 0.44x10(9)/l; P=0.002) and CRP
      levels were higher in patients, but TNFalpha receptor-1 and elastase levels were
      not. Anti-oxLDL antibody levels were similar, as were levels of haptoglobin, IgG
      anti HSP60, IgA and IgG anti-Hsp65 antibodies. Levels of IgA anti-Hsp60
      antibodies were lower in patients (P=0.0001). Logistic regression analysis
      revealed a relationship between periodontitis and HDL (OR 2.15/0.5mmol/l, P=0.02)
      and body mass index (OR 4.54 P=0.005). CONCLUSIONS: Serological differences in
      subjects with periodontitis, some of which involve established risk factors for
      atherosclerosis, might provide insight into the reported epidemiological
      association between periodontitis and cardiovascular disease.

PMID- 14643271
TI  - Chronic periodontitis, a significant relationship with acute myocardial
      infarction.
AB  - BACKGROUND: Chronic periodontitis (CP) has been associated with cardiovascular
      diseases. The study purposes were to identify the odds of acute myocardial
      infarction (AMI) and CP defined at different thresholds. METHODS AND RESULTS: We
      studied 80 subjects with clinically confirmed AMI and 80 matched control subjects
      with no evidence of cardiovascular disease all receiving a comprehensive
      periodontal examination. Statistical analysis demonstrated a difference in the
      proportion of sites with a periodontal probing depth >/=6.0mm (2.7% for non-AMI
      and 12.1% for AMI group, 95% CI: -2.8 to 0.01, P<0.05) but no difference in the
      extent of gingival bleeding was found between groups. The odds ratio of having
      AMI and periodontitis varied between 9.2:1 to 14.1:1 with the greatest odds ratio
      if bone loss exceeded 4mm at >/=50% of the teeth (OR: 14.1:1, 95% CI: 5.5 to
      28.2, P<0.0001). The odds ratio remained significant also when only non-smokers
      were considered (51 subjects) (OR: 7.0:1, 95% CI: 2.0 to 24.3, P<0.01).
      CONCLUSIONS: Our findings suggest that patients who at routine dental visits
      demonstrate evidence of bone loss around several teeth can predictably be
      identified as being at risk for future AMI. Such subjects should be referred for
      medical and periodontal examinations and treatments.

PMID- 14643272
TI  - The angiotensin converting enzyme inhibitor trandolapril has neutral effect on
      exercise tolerance or functional class in patients with myocardial infarction and
      reduced left ventricular systolic function.
AB  - AIMS: To study the effect of angiotensin-converting enzyme (ACE) inhibitor
      trandolapril on exercise tolerance time (ETT) and New York Heart Association
      (NYHA) classification in patients with reduced left ventricular systolic
      dysfunction (LVSD) after acute myocardial infarction (AMI). METHODS AND RESULTS:
      The TRAndolapril Cardiac Evaluation (TRACE) was a randomized controlled study
      designed to evaluate the effect of trandolapril on mortality in 1749 consecutive
      Danish patients with LVSD after AMI. NYHA class was recorded every 3 months in
      all patients. In a prospective sub-study, 254 patients underwent exercise
      tolerance tests at 1, 3 and 12 months. The two treatment arms showed equal
      improvement in NYHA class both in the entire and exclusively symptomatic
      population over 4 years of follow-up (P=ns). ETT increased equally in both
      treatment arms at 1, 3, 12 months (P=ns). A mean of 12mg/day of furosemide was
      spared in trandolapril arm (P=0.001). CONCLUSIONS: Trandolapril had a mild
      diuretic-sparing effect. These results emphasis the importance of explaining to
      patients that ACE inhibitors provide protection against death and hospitalisation
      for heart failure but do not have any significant effect upon symptoms.

PMID- 14643273
TI  - Walk test at increased levels of heart rate in patients with dual-chamber
      pacemaker and with normal or depressed left ventricular function.
AB  - BACKGROUND: This study focuses the role of heart rate on cardiac output (CO) at
      rest and during walk test in patients with dual-chamber pacemaker and depressed
      or normal left ventricular (LV) function. METHODS AND RESULTS: In nine patients
      with ejection fraction (EF) <50% (group A) and in seven with EF 50% (group B)
      haemodynamics were assessed at rest and during three randomized 6-min walk tests
      at fixed rate of 70, 90, and 110beats.min(-1). All patients had dual-chamber
      pacemaker implanted for complete heart block. Left ventricular function was
      monitored by a radionuclide system. In group A, with increasing pacing-rate from
      70 to 110beats.min(-1), CO did not change both at rest and during walk, whereas
      end-systolic volume (ESV) increased (P<0.05) and stroke volume (SV) decreased
      from 68+/-6 to 47+/-9ml at rest (P<0.0001) and from 112+/-21 to 76+/-17ml during
      walk (P<0.005). In group B, with increasing pacing-rate, CO rose from 6.4+/-0.7
      to 9.1+/-1.6l.min(-1)at rest (P<0.001) and from 10+/-1.5 to 14.1+/-2.2l.min(
      1)during walk (P<0.0001), with no change in ESV and SV. CONCLUSIONS: Increasing
      heart rate in presence of ventricular asynchrony induced by dual-chamber pacing
      has negative effect on cardiac contractility and does not improve CO at rest or
      during physical activity in patients with depressed LV function as occurs in
      those with normal function.

PMID- 14643274
TI  - International variation in the use of evidence-based medicines for acute coronary
      syndromes.
AB  - AIMS: We sought to evaluate international patterns of use and factors influencing
      use of evidence-based medications early after ACS. METHODS AND RESULTS: Using a
      database of 15904 ACS patients enrolled in the SYMPHONY and 2nd SYMPHONY trials
      in 37 countries, we performed descriptive and logistic regression analyses. After
      controlling for other factors, region was significantly associated with the use
      of every class of evidence-based medication, most pronounced for intravenous
      unfractionated heparin (IV UFH), low-molecular-weight heparin (LMWH), angiotensin
      II converting enzyme inhibitors (ACEI) and discharge use of lipid-lowering
      agents. Latin America and Eastern Europe were among the highest users of early
      ACEI, yet the lowest users of discharge lipid-lowering therapy. Relative to the
      United States, all regions except Canada had greater use of LMWH and lower use of
      IV UFH. Compared with patients with acute myocardial infarction, those with
      unstable angina less often received aspirin, beta-blockers, ACEI, or IV UFH.
      Older age was associated with lower use of aspirin, beta-blockers, IV UFH, and
      lipid-lowering agents. CONCLUSIONS: Use of evidence-based therapies for
      management of ACS patients is strongly associated with region. To improve patient
      outcomes, more research is needed to understand this variation, and to institute
      appropriate solutions.

PMID- 14643275
TI  - Haemoglobin-related mortality in patients undergoing percutaneous coronary
      interventions.
AB  - AIMS: It has recently been proposed that anaemia is an independent risk factor
      for development of cardiovascular disease in the general population. The impact
      of anaemia on long-term survival of patients with manifest coronary heart disease
      (CHD) has not been assessed so far. In this study, we examined the influence of
      haemoglobin concentrations on the outcome after percutaneous coronary
      interventions (PCI). METHODS AND RESULTS: In a retrospective cohort study, we
      analysed in-hospital and long-term mortality in all male patients admitted to our
      institution for elective PCI from 1998 to 1999. In 689 cases, complete follow-up
      information could be obtained (98.4%). Depending on their baseline haemoglobin,
      patients were divided in quintiles. In all subgroups, angiographic success after
      PCI (90-94%) was comparably high and in-hospital mortality was low (0-0.7%).
      During follow-up (median 697 days), patients in the lowest haemoglobin quintile
      (</=12.9g/dl) were significantly more likely to suffer from all-cause death
      (22.2%) than those of the other quintiles (3.7-12.1%; estimated mortality rates
      from Kaplan-Meier models, P<0.0001, log rank test). In more detail, we found a U
      shaped relationship between mortality and haemoglobin strata in steps of 1g/dl
      (P<0.0001, log rank test). After adjustment for potential co-variates, patients
      of the lowest haemoglobin quintile showed in Cox regression analysis a markedly
      higher risk for death (adjusted hazard rate ratio (HRR) 4.09, 95% confidence
      interval (CI) 1.52-11.05) compared to the quintile with a haemoglobin
      concentration of 14.6-15.2g/dl. CONCLUSIONS: These results indicate that anaemia
      is associated with markedly reduced survival in patients with CHD after elective
      PCI. Since PCI is a common intervention and anaemia is a frequent condition in
      the general population, strategies for the management of anaemic PCI patients and
      treatment of anaemic patients with CHD should be developed.

PMID- 14643276
TI  - Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease.
      Evidence for a disease specific abnormality of the myocardial interstitium.
AB  - AIMS: Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid
      metabolism, is a cause of idiopathic left ventricular hypertrophy but the
      mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular
      magnetic resonance can detect focal myocardial fibrosis. We hypothesised that
      hyperenhancement would be present in AFD. METHODS AND RESULTS: Eighteen males
      (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD
      underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male
      (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/
      5.7%) of total myocardium; in males, percentage hyperenhancement related to LV
      mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular
      volumes. Lesser hyperenhancement was also found in four (50%) heterozygous
      females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake,
      hyperenhancement occurred in the basal infero-lateral wall where, unlike
      myocardial infarction, it was not sub-endocardial. In two male patients with
      severe LVH (left ventricular hypertrophy) and systolic impairment there was
      additional hyperenhancement in other myocardial segments. CONCLUSIONS: These
      observations suggests that myocardial fibrosis occurs in AFD and may contribute
      to the hypertrophy and the natural history of the disease.

PMID- 14643277
TI  - Hotline sessions of the 25th European Congress of Cardiology.

PMID- 14643278
TI  - Psychosocial functioning of adults with congenital heart disease: a neglected
      area.

PMID- 14643280
TI  - Pesticides in Lebanon: a knowledge, attitude, and practice study.
AB  - Pesticides, despite their known toxicity, are widely used in developing
      countries. Evaluating the pattern of their use would be interesting to assess the
      appropriateness of adequate intervention. Using a standardized questionnaire, a
      knowledge, attitude, and practice study was performed in two Lebanese regions, in
      which a group of agricultural workers was compared to workers of the general
      population and a third group of pesticide distributors. Agricultural workers were
      exposed to pesticides during cropping, mixing, loading, and application (100%).
      They had low pesticide knowledge scales compared to pesticide distributors and to
      the general population workers (P<10(-7)). The preventive measures they took were
      low, and the lower their knowledge was, the lower were the preventive measures
      applied (P<10(-3)). Pesticide safety education is necessary in order to induce
      protective behavior among agricultural workers. The general population may also
      benefit from increasing their awareness regarding pesticides.

PMID- 14643281
TI  - Temporal dynamics of emergency department and hospital admissions of pediatric
      asthmatics.
AB  - Asthma is a chronic disease that can result in exacerbations leading to urgent
      care in emergency departments (EDs) and hospitals. We examined seasonal and
      temporal trends in pediatric asthma ED (1997-1999) and hospital (1986-1999)
      admission data so as to identify periods of increased risk of urgent care by age
      group, gender, and race. All pediatric ED and hospital admission data for
      Maryland residents occurring within the state of Maryland were evaluated.
      Distinct peaks in pediatric ED and hospital asthma admissions occurred each year
      during the winter-spring and autumn seasons. Although the number and timing of
      these peaks were consistent across age and racial groups, the magnitude of the
      peaks differed by age and race. The same number, timing, and relative magnitude
      of the major peaks in asthma admissions occurred statewide, implying that the
      variables affecting these seasonal patterns of acute asthma exacerbations occur
      statewide. Similar gross seasonal trends are observed worldwide. Although several
      environmental, infectious, and psychosocial factors have been linked with
      increases in asthma exacerbations among children, thus far they have not
      explained these seasonal patterns of admissions. The striking temporal patterns
      of pediatric asthma admissions within Maryland, as described here, provide
      valuable information in the search for causes.

PMID- 14643282
TI  - DDT induces DNA damage in blood cells. Studies in vitro and in women chronically
      exposed to this insecticide.
AB  - In this study, DDT-induced DNA damage on blood cells was analyzed both in vitro
      and in vivo. Peripheral blood mononuclear cells (PBMC) were isolated from healthy
      donors and incubated in the presence of three different concentrations (40, 80,
      and 100 microg/mL) of p,p'-DDT, p,p'-DDE, and p,p'-DDD at three different
      treatment times (24, 48, and 72 h). Then, DNA damage was assessed by the single
      cell electrophoresis assay (comet assay) as well as by flow cytometry detection
      of hypodiploid cells (DNA content assay). All compounds induced significant DNA
      damage as shown by the comet assay. Accordingly, cells exposed to DDT, DDE, and
      DDD showed a significant increase in the percentage of hypodiploid cells compared
      with untreated PBMC. In agreement with the in vitro data, a significant
      correlation between blood levels of DDT, DDD, and DDE and DNA damage (comet
      assay) was found in women with different amounts of environmental exposure. This
      association remained significant after controlling for nutritional status,
      smoking habits, alcohol ingestion, and reported exposure to other pesticides.
      Although the precise biological importance remains to be explained, our results
      strongly suggest that DDT and its metabolites are able to induce DNA damage in
      PBMC both in vitro and in vivo.

PMID- 14643283
TI  - Environmental exposure to cooking oil fumes and cervical intraepithelial
      neoplasm.
AB  - The fumes from cooking oil, similar to cigarette smoke, contain numerous
      carcinogens such as polycyclic aromatic hydrocarbons, aromatic amines, nitro
      polycyclic aromatic hydrocarbons, etc. In this study, we examined the association
      between exposure to cooking oil fumes and the risk of cervical intraepithelial
      neoplasm. The study population in this nested case-control study consisted of
      women above the age of 19 years living in Chia-Yi County, located in the
      southwestern Taiwan, who had received pap smear screening between October, 1999,
      and December, 2000 (n=32,466). The potential cases were women having lesions
      greater than cervical intraepithelium neoplasm II (> or =CIN2) reconfirmed by
      cervical biopsy (n=116). The potential controls (case: control=1:2) were age
      matched (+/-2 years) and residence-matched women who had normal pap smears within
      6 months of the cases. In total, 100 cases and 197 controls were completely
      interviewed by public health nurses about cooking methods, ventilation, and other
      potential risk factors. Women who cooked at home in a kitchen (n=269) without the
      presence of a fume extractor at least once a week between the ages of 20 and 40
      had a 2.29 times higher risk [95% confidence interval (CI)=1.08-4.87] of
      developing cervical intraepithelial neoplasm than those who did not cook once a
      week in such a kitchen during the same age span, after adjusting for other
      potential confounders. This finding was further strengthened by the finding that
      women who did not use the fume extractors had a 2.47 times higher risk (95%
      CI=1.15-5.32) of developing cervical intraepithelial neoplasm than women who
      cooked in kitchens with fume extractors that were always switched on while
      cooking. We also found a joint protective effect of fume extractor use among
      women older than 40 years (n=202) if they used the extractors during both age
      spans of their lives, ages 20-40 and >40 years. Comparing our findings on women
      more than 40 years old who used fume extractors during both periods, we found a
      2.05-fold greater risk (95% CI=0.86-4.86) for those who used exhaust fans during
      only one of the two age spans and a 3.46-fold greater risk in those who had not
      used an exhaust fan for either period (95% CI=1.08-11.10) (trend test, P=0.02).
      While exposure to cooking oil fumes may cause cervical intraepithelial neoplasm,
      women can be protected from this risk by always cooking in kitchens equipped with
      fume extractors and by keeping them on while cooking.

PMID- 14643284
TI  - Ecological association of water hardness with prevalence of childhood atopic
      dermatitis in a Japanese urban area.
AB  - The prevalence of symptoms of atopic eczema among Japanese children aged 6-7
      years is the second highest in 56 countries. Reasons for such a high prevalence
      are unknown. This ecological study examined whether the positive association of
      water hardness with atopic dermatitis among British primary-school children also
      exists in Japan. Study subjects were 458,284 of 489,725 children, aged 6-12
      years, in 1,016 public elementary schools in Osaka Prefecture with 44
      municipalities. The study used data on water hardness and chlorine content of the
      water supply; prevalence of atopic dermatitis diagnosed by physicians and
      episodes of wheezing reported by the parents; and potential confounding factors
      by socioeconomic and health care status per municipality. The prevalence of
      atopic eczema was significantly higher in the highest water hardness category
      than that in the lowest (24.4% [n=2,288/9,362] and 22.9% [n=77,408/33,8267],
      respectively; adjusted odds ratio 1.12, 95% confidence interval 1.06-1.18;
      P<0.0001 for trend). A significant and slightly J-shaped relationship between
      chlorine content of the water supply and prevalence of atopic dermatitis was
      observed after adjustment for confounding factors. There were no apparent
      associations of water hardness and chlorine content of the water supply with
      prevalence of wheeze. Water hardness may increase the risk of atopic dermatitis
      among elementary-school children in Japan, as well as in the United Kingdom.

PMID- 14643285
TI  - DDT induces apoptosis in human mononuclear cells in vitro and is associated with
      increased apoptosis in exposed children.
AB  - The aim of the present work was to investigate whether DDT and its metabolites
      are able to induce apoptosis of human peripheral blood mononuclear cells (PBMC)
      both in vitro and in vivo. Cells isolated from healthy individuals were incubated
      in the presence of increasing concentrations of p'p-DDT, p'p-DDE, or p'p-DDD (0
      150 microg/mL) for different intervals. Apoptosis was then determined by flow
      cytometry (DNA cell content analysis) and fluorescence microscopy (Hoechst
      staining). A significant level of apoptosis was induced by DDT, DDD, and DDE at
      80 microg/mL compared to controls, reaching a maximum effect at 100 microg/mL. We
      began to detect apoptosis at 12h, with a maximum effect at 24h of incubation.
      These results were confirmed using the TUNEL assay in cells treated with the
      three compounds tested as well as with o'p-DDT at 100 microg/mL and 24h of
      incubation. Our data demonstrate that DDT and its metabolites are able to induce
      apoptosis of human PBMC in vitro. Therefore, we performed a preliminary study in
      children exposed to this insecticide. When compared to a control population, the
      exposed children had higher levels of DDT, DDD, and DDE in blood and also had a
      higher frequency of apoptosis. In the exposed children, a weak positive
      association was found between the frequency of apoptosis and the exposure to DDT
      and DDE. Our results showed that more studies are needed in people exposed to
      DDT, as apoptosis may cause serious public health effects such as
      immunosuppression.

PMID- 14643286
TI  - Multipathway risk assessment on disinfection by-products of drinking water in
      Hong Kong.
AB  - The lifetime cancer risk and the hazard index of trihalomethanes (THMs) through
      oral ingestion, dermal absorption, and inhalation exposure from tap water in 19
      districts in Hong Kong are estimated. The most dominant THMs are chloroform and
      bromodichloromethane (BDCM) in Hong Kong tap water. Among the three different
      pathways, residents have a higher risk of cancer through oral ingestion than
      through the other two pathways. The lifetime cancer risks through oral ingestion
      and dermal absorption for BDCM make the highest percentage contribution (59%) to
      total risks, followed by chloroform (24%). The chloroform and BDCM are at or
      above the negligible risk level of 10(-6) by a factor of 10 or more in most
      districts. Among the 19 districts, people living in Sai Kung have the highest
      risk of cancer due to the THM exposure through the multipathways, mainly because
      of the exposure to BDCM and dibromochloromethane (DBCM). The total cancer risk
      analysis indicates that each year approximately 10 out of the seven million Hong
      Kong residents could get cancer from the daily intake of water.

PMID- 14643287
TI  - Risk assessment of exposure to volatile organic compounds in different indoor
      environments.
AB  - The lifetime cancer risks of exposure of cooks and food service workers, office
      workers, housewives, and schoolchildren in Hong Kong to volatile organic
      compounds (VOCs) in their respective indoor premises during normal indoor
      activities were assessed. The estimated cancer risk for housewives was the
      highest, and the second-highest lifetime cancer risk to VOC exposure was for the
      groups of food service and office workers. Within a certain group of the
      population, the lifetime cancer risk of the home living room was one to two
      orders of magnitude higher than that in other indoor environments. The estimated
      lifetime risks of food service workers were about two times that of office
      workers. Furthermore, the cancer risks of working in kitchen environments were
      approximately two times higher than the risks arising from studying in air
      conditioned classrooms. The bus riders had higher average lifetime cancer risks
      than those travelling by Mass Transit Railway. For all target groups of people,
      the findings of this study show that the exposures to VOCs may lead to lifetime
      risks higher than 1 x 10(-6). Seven indoor environments were selected for the
      measurement of human exposure and the estimation of the corresponding lifetime
      cancer risks. The lifetime risks with 8-h average daily exposures to individual
      VOCs in individual environments were compared. People in a smoking home had the
      highest cancer risk, while students in an air-conditioned classroom had the
      lowest risk of cancer. Benzene accounted for about or more than 40% of the
      lifetime cancer risks for each category of indoor environment. Nonsmoking and
      smoking residences in Hong Kong had cancer risks associated with 8-h exposures of
      benzene above 1.8 x 10(-5) and 8.0 x 10(-5), respectively. The cancer risks
      associated with 1,1-dichloroethene, chloroform, methylene chloride,
      trichloroethene, and tetrachloroethene became more significant at selected homes
      and restaurants. Higher lifetime cancer risks due to exposure to styrene were
      only observed in the administrative and printing offices and air-conditioned
      classrooms. Higher lifetime cancer risks related to chloroform exposures were
      observed at the restaurant and the canteen.

PMID- 14643288
TI  - Atmospheric concentrations of the Cl atom, ClO radical, and HO radical in the
      coastal marine boundary layer.
AB  - Atmospheric concentrations of chlorine atom (Cl*), chlorine monoxide radical
      (ClO*), and hydroxyl radical (HO*) in the coastal marine boundary layer are
      estimated in this study. A steady-state approach to their concentrations in
      equilibrium with other atmospheric chemical species is used. Measurements of
      atmospheric trace species, HCl, Cl2, HCHO, H2O2, CH3OOH, CH4, CO, SO2, NO, NO2,
      and O3, were performed at four sites in Taiwan during the spring of 1999. The
      results indicate that the concentrations of the Cl* atom and the ClO* and HO*
      radicals decrease significantly with cloud cover. The calculated average daytime
      concentrations of Cl*, ClO*, and HO* are 3 x 10(5), 1 x 10(7), and 6 x 10(5)
      molecules/cm3, respectively. Due to the high reactivity of Cl* with hydrocarbons
      and its concentration level competitive to that of HO*, Cl* should be a
      significant sink for hydrocarbons in these cases.

PMID- 14643289
TI  - A comparison of indoor air pollutants in Japan and Sweden: formaldehyde, nitrogen
      dioxide, and chlorinated volatile organic compounds.
AB  - Indoor and outdoor concentrations of formaldehyde (HCHO), nitrogen dioxide (NO2),
      and selected chlorinated volatile organic compounds (chlorinated VOC) were
      measured in 37 urban dwellings in Nagoya, Japan, and 27 urban dwellings in
      Uppsala, Sweden, using the same sampling procedures and analytical methods.
      Indoor as well as outdoor air concentrations of HCHO, NO2, and chlorinated VOC
      were significantly higher in Nagoya than in Uppsala (P<0.01), with the exception
      of tetrachlorocarbon in outdoor air. In Nagoya, HCHO and NO2 concentrations were
      significantly higher in modern concrete houses than in wooden houses and higher
      in newer (less than 10 years) than in older dwellings (P<0.01), possibly due to
      less natural ventilation and more emission sources in modern buildings. Dwellings
      heated with unvented combustion sources had significantly higher indoor
      concentrations of NO2 than those with clean heating (P<0.05). Moreover, dwellings
      with moth repellents containing p-dichlorobenzene had significantly higher indoor
      concentrations of p-dichlorobenzene (P<0.01). In conclusion, there appear to be
      differences between Nagoya and Uppsala with respect to both indoor and outdoor
      pollution levels of the measured pollutants. More indoor pollution sources could
      be identified in Nagoya than in Uppsala, including construction and interior
      materials emitting VOC, use of unvented combustion space heaters, and moth
      repellents containing p-dichlorobenzene.

PMID- 14643290
TI  - Evidence of histamine receptors in fish brain using an in vivo [14C]2
      deoxyglucose autoradiographic method and an in vitro receptor-binding
      autoradiographic method.
AB  - It was hypothesized that fish possess functioning H1 histamine receptors that
      have the ability to bind agonists and antagonists specific to the H1 histamine
      receptor subtype. For these experiments, a combination of a novel, in vivo 2
      deoxyglucose method and a standard in vitro autoradiography procedure was
      utilized. A regional, statistically significant dose response in neurological
      functioning was observed when fish were exposed to histaminergic agents (i.e., H1
      agonists and antagonists), which created the first neurological profile for the
      H1 histamine receptor in fish brain. The H1 histamine receptor was chosen as a
      characterization receptor in fish because histamine has been linked to a variety
      of neurological functions such as the control of arousal, attention, sensory
      processing, and cognition. Histamine also plays a role in pituitary hormone
      secretion, appetite control, and, potentially, regulation of vestigular
      reactivity. In addition, the fish brain is well characterized structurally, and
      the existence of an H3-like receptor has been documented recently in zebrafish.
      However, to date there is little detailed information about specific localization
      and functioning of the H1 histamine receptor in fish.

PMID- 14643291
TI  - Contamination with nonessential metals from a solid-waste incinerator correlates
      with nutritional and immunological stress in prefledgling black kites (Milvus
      migrans).
AB  - We assessed whether levels of heavy metals in blood have detrimental effects on
      the health of prefledgling black kites (Milvus migrans) exposed to emissions from
      a solid waste incinerator near Madrid, central Spain. As health indexes, we
      considered body mass corrected by structural size as a general indicator of
      nutritional condition and white blood cell counts (especially the
      heterophil:lymphocyte ratio) as an indirect measure of immune function.
      Nutritional condition was positively related to levels of Zn, an essential
      element with a major role in many physiological pathways, while the opposite
      trend was found for the essential Cu, the concentration of which tends to
      increase with decreasing nutritional condition. We found an interaction between
      Zn and Cd, indicating that high levels of Zn produce smaller effects of Cd on
      body mass. Potential immunological stress, expressed as an increase in the
      heterophil:lymphocyte ratio, caused by the toxic Cd increased as levels of Cu
      decreased. Thus, nestlings with low levels of Cu and poor nutritional condition
      suffered more immunological stress due to Cd contamination than nestlings with
      higher levels of Cu. We also found a negative interaction between Zn and Cd,
      indicating a response of essential Zn to increasing levels of Cd, which may be
      indicative of the negative effects of Cd on the immune system. These results
      suggest that the participation of metallothioneins in detoxification and metal
      regulation may also indirectly enhance the adrenal stress response to
      contaminants, probably through a competition of Cd and Zn for Zn binding sites on
      metallothioneins, reducing the ability of Cd to stress the immune system.

PMID- 14643292
TI  - Bisphenol A induces feminization in Xenopus laevis tadpoles.
AB  - To evaluate possible estrogenic effects of bisphenol A (BPA) in an amphibian
      model, Xenopus laevis tadpoles were exposed to BPA and 17beta-estradiol (E2)
      during larval development. After metamorphosis, the gonadal phenotype was
      determined by gross morphology, and testes were further examined histologically
      to validate the results. BPA treatment altered the normal sex ratio toward
      females depending on the BPA concentrations added. Chemical analysis showed a
      time-dependent decline of BPA during semistatic exposure, indicating that BPA is
      taken up and metabolized to some extent by tadpoles. In addition, tadpoles were
      exposed to BPA and E2 for 2 weeks during sensitive stages of sexual
      differentiation. Afterward, the expression of an estrogenic biomarker, estrogen
      receptor (ER) mRNA, was assessed by semiquantitative RT-PCR. Both BPA and E2 up
      regulated ER mRNA significantly. In conclusion, these results show clear evidence
      that BPA induces feminization in X. laevis tadpoles, revealing an estrogenic
      potency of BPA that influences sexual development in amphibians.

PMID- 14643293
TI  - Resistance to imatinib (Glivec): update on clinical mechanisms.
AB  - Imatinib mesylate, an orally administered 2-phenylaminopyrimidine derivative that
      inhibits BCR/ABL tyrosine kinase activity, has shown great promise in the
      treatment of chronic myelogenous leukemia (CML). This small molecule, tyrosine
      kinase inhibitor, has also been shown to be effective against metastatic
      gastrointestinal stromal tumors (GISTs) expressing the stem cell factor (SCF)
      receptor kit. However, the threat of resistance in patients has prompted
      investigators to uncover the mechanisms whereby malignant cells develop
      resistance to imatinib, and has also led to the establishment of strategies
      designed to over-ride imatinib resistance. Here, we provide a comprehensive
      overview of the effectiveness of imatinib in the treatment of chronic,
      accelerated and blast crisis-phase CML, Philadelphia chromosome-positive (Ph+)
      acute lymphoid leukemia (ALL) and metastatic GIST. Established mechanisms of
      resistance to imatinib are discussed, as are novel therapeutic approaches to
      improving drug responsiveness by reversing development of imatinib resistance in
      patients.

PMID- 14643294
TI  - Potential drug targets in cyst-wall biosynthesis by intestinal protozoa.
AB  - Given that resistance to antiprotozoal drugs exists and is likely to increase and
      given that currently no reliable treatments exist for some of these infections,
      efforts to find new targets for chemotherapy must be continued. In the case of
      cyst-forming pathogenic protozoa, one such target might be encystment pathways
      and cyst-wall assembly. Information is increasing on protozoan encystment and, as
      it does, we can begin to answer the question of whether targeting it for
      chemotherapy is a viable drug strategy. Currently, there are significant efforts
      to understand encystment in Giardia and Entamoeba, and potential targets are
      being discovered as work on their encystment mechanisms progress. We know with
      certainty now that Giardia and Entamoeba cyst walls contain unique proteins and
      polysaccharides which differ from those of their hosts and thus make them
      potentially interesting targets for a variety of chemotherapeutic attacks.
      Although we lack detailed information about the other protozoan cyst formers,
      enough evidence exists for Giardia and Entamoeba that it seems prudent to screen
      them with some of the antifungal drugs, especially those that target
      mannoproteins, chitin synthesis, and beta (1, 3) glucan synthesis to ascertain if
      they target elements in these protozoan pathways that are similar to those found
      in fungi.

PMID- 14643295
TI  - Apoptotic pathways activated by histone deacetylase inhibitors: implications for
      the drug-resistant phenotype.
AB  - Histones are abundant proteins that coordinate the organization of eukaryotic
      nucleosomes. Post-translational modifications of histones-acetylation,
      phosphorylation and methylation-locally modulate the higher order nucleosome
      structure. Acetylation and deacetylation of histones occur at their N-terminal
      tails in a dynamic fashion and influence DNA accessibility to factors regulating
      replication, repair and transcription. Acetylation, catalyzed by histone
      acetyltransferases (HATs) on the epsilon-NH(2) group of lysine residues,
      neutralizes the positive charge and thereby triggers transcriptional activation.
      Deacetylation, catalyzed by histone deacetylases (HDACs) on the same lysine
      residues, unmasks the charge and triggers transcriptional repression. Inhibition
      of HDACs has thus a broad effect on chromatin architecture, and possibly on
      protein function, and multiple effects on cell growth. HDAC inhibitors (HDIs) are
      promising as single anti-cancer agents and in combination therapies.
      Understanding of the molecular basis for HDIs action is needed to better design
      the clinical antitumor treatments. The apoptotic pathways induced by HDIs are
      emerging and we provide an overview of the recent findings that regard apoptotic
      key elements. We also propose that transformed cells discern the widespread
      effect of HDIs on chromatin architecture as a genotoxic insult to respond to
      through induction of apoptosis.

PMID- 14643296
TI  - Combination chemotherapy for invasive fungal infections: what laboratory and
      clinical studies tell us so far.
AB  - Despite potential benefits, few objective clinical data (with the exception of
      cryptococcocal meningitis) are available supporting the routine use of
      combination antifungal regimens in patients with invasive mycoses, importantly
      aspergillosis or candidiasis. There is considerable debate on what constitutes
      synergy or antagonism in vitro and whether these laboratory findings are
      translated to beneficial interactions in patients. Given the lack of rigorous
      clinical data, a better understanding of the important concepts for the
      justification of the clinical and pharmacoeconomic threshold of antifungal
      therapy is needed. Such concepts include standardized methods for screening
      antifungal combinations in culture or in animals and collaborative efforts to
      collect clinical data on the efficacy and safety of combination regimens.

PMID- 14643297
TI  - Liposome-based approaches to overcome anticancer drug resistance.
AB  - Drug resistance remains an important obstacle towards better outcomes in the
      treatment of cancer. One general approach to overcome this problem has been to
      inhibit specific resistance mechanisms, such as P-glycoprotein (PGP)-mediated
      drug efflux, using small molecule agents or other therapeutic strategies.
      Alternatively, drug delivery approaches using liposomes or other carriers can in
      principle target drugs to tumor tissue, tumor cells, or even compartments within
      tumor cells. By increasing bioavailability of drugs at sites of action, these
      approaches may provide therapeutic advantages, including enhanced efficacy
      against resistant tumors. Current liposomal anthracyclines have achieved clinical
      use in cancer treatment by providing efficient encapsulation of drug in stable
      and non-reactive carriers, and there is evidence indicating potential benefit in
      some clinical settings involving resistant tumors. Other liposome-based
      strategies include constructs designed to be taken up by tumor cells, as well as
      further modifications to allow triggered drug release. These approaches seek to
      overcome drug resistance by more efficient delivery to tumor cells, and in some
      cases by concomitant avoidance or inhibition of drug efflux mechanisms. Newer
      agents employ molecular targeting, such as immunoliposomes using antibody
      directed binding and internalization. These agents selectively deliver drug to
      tumor cells, can efficiently internalize for intracellular drug release, and can
      potentially enhance both efficacy and safety.

PMID- 14643298
TI  - Drug transport and drug resistance in African trypanosomes.
AB  - Drug resistance in African trypanosomes has been studied for almost a hundred
      years. Beginning with Paul Ehrlich's work that led to the chemoreceptor
      hypothesis, reduction of net drug uptake has emerged as the most frequent cause
      of resistance. This review, therefore, focuses on trypanosomal drug transporter
      genes. TbAT1 encodes purine permease P2, which mediates influx of melarsoprol and
      diamidines. Disruption of TbAT1 in Trypanosoma brucei reduced sensitivity to
      these trypanocides. TbMRPA encodes a putative trypanothione-conjugate efflux
      pump, and overexpression of TbMRPA in T. brucei causes melarsoprol resistance. It
      will be important to determine the role of TbAT1 and TbMRPA in sleeping sickness
      treatment failures.

PMID- 14643299
TI  - On the role of APC-activation for in vitro versus in vivo T cell priming.
AB  - Professional antigen-presenting cells take up antigens for processing and
      presentation in association with MHC class I and II molecules. When APCs receive
      the right stimuli, they undergo a maturation process and migrate to secondary
      lymphoid organs to trigger T cell activation. In this study, we compared side-by
      side in vivo and in vitro activation of T cells. Transgenic CD8(+) T cells
      specific for the p33 epitope, derived from the lymphocytic choriomeningitis virus
      glycoprotein, were labeled with CFSE and injected into syngeneic mice or
      alternatively, co-cultured in vitro with APCs. The p33 epitope was delivered as
      free peptide or genetically fused to virus-like particles. Whereas proliferation
      of specific T cells was comparable in both systems, the production of IFN-gamma
      and the expression of CD25 showed important differences. Induction of effector
      function and expression of activation markers were strongly enhanced in vitro by
      both the free peptide and VLPs. Surprisingly, addition of CpG-containing immune
      stimulating DNA for activation of APCs dramatically increased effector T cell
      differentiation in vitro, whereas no enhancement could be observed in vitro.
      Thus, activation of professional APCs was mandatory for induction of effector
      CD8(+) T cell responses in vivo, while this step was largely dispensable in
      vitro.

PMID- 14643300
TI  - Mechanisms of increased immunogenicity for DNA-based vaccines adsorbed onto
      cationic microparticles.
AB  - Investigation into the mechanism of action of vaccine adjuvants provides
      opportunities to define basic immune principles underlying the induction of
      strong immune responses and insights useful for the rational development of
      subunit vaccines. A novel HIV vaccine composed of plasmid DNA-encoding p55 gag
      formulated with poly-lactide-co-glycolide microparticles (PLG) and cetyl
      trimethyl ammonium bromide (CTAB) elicits both serum antibody titers and
      cytotoxic lymphocyte activity in mice at doses two orders of magnitude lower than
      those required for comparable response to plasmid DNA in saline. Using this
      model, we demonstrated the increase in potency requires the DNA to be complexed
      to the PLG-CTAB microparticles. Furthermore, the PLG-CTAB-DNA formulation
      increased the persistence of DNA at the injection site, recruited mononuclear
      phagocytes to the site of injection, and activated a population of antigen
      presenting cells. Intramuscular immunization with the PLG-CTAB-DNA complex
      induced antigen expression at both the injection site and the draining lymph
      node. These findings demonstrate that the PLG-CTAB-DNA formulation exhibits
      multiple mechanisms of immunopotentiation.

PMID- 14643301
TI  - Accelerated antigen presentation and elicitation of humoral response in vivo by
      FcgammaRIIB- and FcgammaRI/III-mediated immune complex uptake.
AB  - It is well established that activating-type Fc receptors for IgG (FcgammaR), such
      as FcgammaRI and FcgammaRIII, are essential for inducing inflammatory responses,
      whereas a unique inhibitory FcgammaR, FcgammaRIIB, inhibits intracellular
      signaling upon ligation of IgG-immune complexes, and can suppress inflammation
      and autoimmunity. Although antigen presentation is a crucial step for evoking
      inflammatory responses, the contribution of FcgammaRIIB to antigen presentation
      is controversial as to whether it regulates antigen-presenting cells (APC),
      particularly dendritic cells (DC), positively or negatively. In the present
      report, we show that the antigen targeting to both activating-type FcgammaRs,
      FcgammaRI/III, and inhibitory FcgammaRIIB on bone marrow-derived DC and
      macrophages and primary epidermal Langerhans' cells augmented T cell
      proliferation in vitro and elicited humoral responses upon adoptive transfer of
      the antigen-pulsed DC. The DC lacking FcgammaRIIB showed a reduction in IC-uptake
      ability and a decreased T-cell stimulation, and induced less efficient IgG
      production than those of DC from wild-type mice. On the other hand, the DC
      lacking FcR common gamma subunit, which only expresses FcgammaRIIB, showed
      significant up-regulations of IC-uptake, T-cell proliferation, and IgG production
      compared to those of FcgammaR null DC, demonstrating a positive regulation of
      FcgammaRIIB for the efficient antigen presentation of IgG-complexed antigens.
      These results support the therapeutic benefits of antigen-targeting to FcgammaR
      on APC in the various inflammatory disorders.

PMID- 14643302
TI  - Cell cycle block in anergic T cells during tolerance induction.
AB  - The induction of anergy, or T cell unresponsiveness to antigen, is preceded by T
      cell activation and cell division in response to fed antigens. These events
      parallel the activation observed in T cells following sensitization with antigen
      and adjuvant. The events that distinguish eventual sensitization versus tolerance
      remain unclear. Using a T lymphocyte transfer model specific to OVA, we
      demonstrated previously that oral encounter with antigen leads to functional
      anergy. Antigen-specific CD4+ T cells nevertheless become activated and cycle
      briefly after encounter with antigen. In this study, we measured the extent of
      cell cycling of antigen-specific T cells after oral encounter with their antigen.
      Whereas T cells cycle on the average of eight times in 4 days after conventional
      immunization, an abortive proliferation was observed in the draining LN T cells
      after oral encounter with antigen; OVA-specific T cells divided fewer times after
      exposure to fed OVA, compared to T cells in mice immunized with OVA. This
      abortive proliferation is antigen specific and not due to bystander suppression,
      as coadministration of an unrelated antigen that was previously used as a
      tolerogen does not alter the degree of abortive proliferation. Measurement of
      BrdU incorporation in mice that were previously fed ovalbumin indicates that up
      to 3 days following feeding, OVA-specific cells are actively cycling in vivo.
      However, by day 4, they have stopped cycling while identical T cells in OVA
      sensitized mice continue to cycle. Our results indicate either that tolerance is
      a default pathway and a secondary stimulus is required at day 3 to progress to
      sensitization, or that elements that limit cell cycle progression are provided
      for tolerance induction.

PMID- 14643303
TI  - Activation induced differential regulation of stem cell antigen-1 (Ly-6A/E)
      expression in murine B cells.
AB  - Expression of stem cell antigen-1 (Ly-6A/E) is developmentally regulated in
      murine B cells. However, little is known about its modulation during B cell
      activation. We report here the differential regulation of Ly-6A/E expression in
      response to diverse activation signals in mature B cells. Stimulation of resting
      B cells through the antigen receptor (BCR) inhibited, Ly-6A/E surface expression
      in dose dependent manner. Activation induced downregulation of Ly-6A/E is
      specific to BCR mediated signaling events as stimulation of B cells with anti
      CD40, lipopolysaccharide or interferon-gamma induced upregulation of Ly-6A/E
      surface expression. The activation induced differential modulation of Ly-6A/E
      expression is mediated at the mRNA levels. A role for BCR signaling in inhibition
      of Ly-6A/E expression was further confirmed using STAT-1(-/-) B cells, which
      expressed constitutive, but not inducible Ly-6A/E. The BCR induced inhibition of
      Ly-6A/E RNA and surface expression was mimicked by ionomycin, but not phorbol
      myristate acetate, indicating a role for calcium but not protein kinase C
      dependent signaling events. Inhibition of calcineurin reversed the BCR or
      ionomycin inhibited Ly-6A/E expression. Interestingly, in vitro differentiation
      analysis of Ly-6A/E(+) and Ly-6A/E(-) splenic B cells revealed the Ly-6A/E(+)
      cells to be the major source of antibody production, suggesting a potential role
      for Ly-6A/E in B cell differentiation. These studies provide the first evidence
      for activation induced differential modulation and differentiation of Ly-6A/E(+)
      B cells.

PMID- 14643306
TI  - Phenolics with PPAR-gamma ligand-binding activity obtained from licorice
      (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically
      diabetic KK-A(y) mice.
AB  - The EtOAc extract of licorice (Glycyrrhiza uralensis roots) exhibited
      considerable PPAR-gamma ligand-binding activity. Bioassay-guided fractionation of
      the extract using a GAL-4-PPAR-gamma chimera assay method resulted in the
      isolation of two isoflavenes, one of which is a new compound named
      dehydroglyasperin D, an isoflavan, two 3-arylcoumarins, and an isoflavanone as
      the PPAR-gamma ligand-binding active ingredients of licorice. The isoprenyl group
      at C-6 and the C-2' hydroxyl group in the aromatic ring-C part in the isoflavan,
      isoflavene, or arylcoumarin skeleton were found to be the structural requirements
      for PPAR-gamma ligand-binding activity. Glycyrin, one of the main PPAR-gamma
      ligands of licorice, significantly decreased the blood glucose levels of
      genetically diabetic KK-A(y) mice.

PMID- 14643304
TI  - Comparable in vivo efficacy of CD28/B7, ICOS/GL50, and ICOS/GL50B costimulatory
      pathways in murine tumor models: IFNgamma-dependent enhancement of CTL priming,
      effector functions, and tumor specific memory CTL.
AB  - Increasing evidence suggests that B7/CD28 interactions are important in clonal
      expansion and effector function of nai;ve CD4(+) T cells, whereas ICOS/GL50
      interactions may optimize the responses of recently activated T(H) cells. In
      tumor models, it has been shown that engagement of ICOS, like CD28, by its
      ligands can be effective in enhancing tumor immunity. In this report, we have
      directly compared the in vivo efficacy of CD28 vs ICOS activation in the MethA
      fibrosarcoma and B16F1 melanoma tumor models. We studied the efficacy of systemic
      treatment of tumors with murine B7.2-IgG or GL50-IgG fusion proteins, and the
      therapeutic potential of B7.1 or GL50 vaccines given during various phases of the
      antitumor responses. In addition, we compare the efficacy of ICOS-ligand splice
      variants GL50 and GL50B in promoting tumor immunity. We find that each of these
      pathways is equally effective in promoting tumor immunity and that the efficacy
      of both GL50 and B7.1 vaccines is IFN-gamma but not IL-10 dependent. Our results
      suggest that CD28 or ICOS costimulation-based strategies may be equally
      efficacious as adjuvants to conventional cancer treatment.

PMID- 14643307
TI  - KMI-008, a novel beta-secretase inhibitor containing a hydroxymethylcarbonyl
      isostere as a transition-state mimic: design and synthesis of substrate-based
      octapeptides.
AB  - A novel class of substrate-based beta-secretase (BACE1) inhibitors containing a
      hydroxymethylcarbonyl (HMC) isostere was designed and synthesized.
      Phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] was an
      effective transition-state mimic at the P(1) position. Structure-activity
      relationships (SARs) of the P(3)-P(3)' positions of BACE1 inhibitors were
      studied.

PMID- 14643308
TI  - A simple stereoselective synthesis and biological evaluation of FR181157: orally
      active prostacyclin mimetic.
AB  - Synthetic method of a novel prostaglandin (PG) mimetic: FR181175 without PG
      skeleton are described. The key to success is creation of a chiral epoxide using
      Sharpless AD reaction with high ee yield. FR181157 shows high potency and agonist
      efficacy at the IP receptor and has good bioavailability.

PMID- 14643309
TI  - B-ring unsaturated estrogens: biological evaluation of 17alpha-Dihydroequilein
      and novel B-Nor-6-thiaequilenins as tissue selective estrogens.
AB  - The pharmacology and SAR of representative equine estogens is described. 17alpha
      Dihydroequilenin was found to prevent bone loss after 5 weeks of oral
      administration to ovariectomized rats. The stereochemical significance of the D
      ring and the C/D ring juncture was investigated with a series of benzothiophene
      based equilenin analogues.

PMID- 14643310
TI  - Non-peptide alpha(v)beta(3) antagonists: identification of potent, chain
      shortened RGD mimetics that incorporate a central pyrrolidinone constraint.
AB  - Antagonists of the integrin receptor alpha(v)beta(3) are expected to have utility
      in the treatment of osteoporosis through inhibition of bone resorption. A series
      of potent, chain-shortened, pyrrolidinone-containing alpha(v)beta(3) receptor
      antagonists is described. Two sets of diasteromeric pairs of high-affinity
      antagonists demonstrated marked differences in log P values, which translated
      into differing dog pharmacokinetic properties. One member of this set was
      demonstrated to be effective in reducing bone resorption in rats.

PMID- 14643311
TI  - Lysine sulfonamides as novel HIV-protease inhibitors: optimization of the
      Nepsilon-acyl-phenyl spacer.
AB  - A series of Nalpha-isobutyl-Nalpha-arylsulfonamido-(Nepsilon acyl) lysine and
      lysinol derivatives were prepared and evaluated as inhibitors of HIV protease and
      wild type virus. A simple original synthesis was devised to form Nalpha
      (arylsulfonamide)-Nalpha-isobutyl lysine, which could be easily acylated with
      carboxylic acids at the Nepsilon position. A two-atom spacer was found to be
      optimal between this acyl group and a phenyl yielding compounds of sub-nanomolar
      potency on purified enzyme.

PMID- 14643312
TI  - Rational design, synthesis and structure-activity relationships of a cyclic
      succinate series of TNF-alpha converting enzyme inhibitors. Part 1: lead
      identification.
AB  - Rational design based on the broad spectrum MMP inhibitor CGS 27023A led to the
      identification of a novel series of cyclic succinate TACE inhibitors. As a
      mixture of two enantiomers, the lead compound 17b exhibited potent enzyme
      activity (IC(50)=8 nM) in the inhibition of porcine TNF-alpha converting enzyme
      (pTACE) and excellent selectivity over aggrecanase and MMP-1, -2 and -9.

PMID- 14643313
TI  - Rational design, synthesis and structure-activity relationships of a cyclic
      succinate series of TNF-alpha converting enzyme inhibitors. Part 2: lead
      optimization.
AB  - Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-[[4-(4
      quinolinyloxymethyl)anilinyl]carbonyl]-1-cyclohexanecarboxamide) at the
      cyclohexyl ring and the quinoline moiety led to the identification of a series of
      piperidine containing TACE inhibitors with potent activity in the inhibition of
      TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491
      [N-hydroxy-(5S,6S)-1-methyl-6-[[4-(2-methyl-4
      quinolinylmethoxy)anilinyl]carbonyl]-5-piperidinecarboxamide] exhibited an IC(50)
      value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is
      orally bioavailable with an F value of 43% in beagle dogs.

PMID- 14643314
TI  - Fluorescence resonance energy transfer in a novel cyclodextrin-peptide conjugate
      for detecting steroid molecules.
AB  - A novel cyclodextrin conjugated peptide, 1, having two different fluorophores,
      coumarin and pyrene, in the side chains has been designed and synthesized. The
      circular dichroism study reveals that 1 shows typical alpha-helix pattern, and
      forms intramolecular inclusion complex with coumarin. The fluorescence emission
      study shows that the peptide exhibits intramolecular fluorescence resonance
      energy transfer (FRET) without quenching of two fluorophores. We have determined
      the binding constants of 1 for various biologically important steroid molecules
      as guests using the guest-responsive variation in the fluorescence emission
      intensity of coumarin.

PMID- 14643315
TI  - 3-iodo-4-phenoxypyridinones (IOPY's), a new family of highly potent non
      nucleoside inhibitors of HIV-1 reverse transcriptase.
AB  - Building upon the potent anti-HIV-1 activities observed for the 3-dimethylamino-4
      benzylpyridinone 2, and the corresponding 4-aryloxypyridinone analogue 3, a
      concise and efficient route to the 3-iodo-4-aryloxypyridinones 14a-c (IOPY's) was
      developed. This involved reaction of the 4-hydroxy substituted pyridinone 10 with
      the requisite dichloroiodobenzene reagent 11. IOPY compound 14c is active at
      IC(50)=1-45 nM against wild type HIV-1 and a panel of six major simple/double HIV
      mutant strains.

PMID- 14643316
TI  - 6-(2-adamantan-2-ylidene-hydroxybenzoxazole)-O-sulfamate: a potent non-steroidal
      irreversible inhibitor of human steroid sulfatase.
AB  - We report the synthesis and results from the in vitro evaluation of 6-(adamantan
      2-ylidene-hydroxybenzoxazole)-O-sulfamate 1 as an irreversible inhibitor of human
      steroid sulfatase (STS). Highly straightforward, condensation of 2-methyl-6
      hydroxybenzoxazole with 2-adamantanone, subsequent elimination of water and
      sulfamoylation provide the title compound in 45% overall yield from the
      inexpensive 2,4-dihydroxyacetophenone. 1 was found to be a potent irreversible
      inhibitor of purified human steroid sulfatase (STS) and specific for this enzyme
      relative to human arylsulfatases A and B. In cellular assays with human
      keratinocytes, sebocytes and fibroblasts, 1 blocked STS activity with IC(50)
      values in the range of 0.15-0.8 nM, and in MCF-7 breast cancer cells with
      IC(50)=2.3 nM, while it did not bind to estrogen receptors alpha and beta. Thus,
      1 is a candidate for further investigation of its potential as a drug to be used
      in androgen- and estrogen-dependent diseases.

PMID- 14643317
TI  - 4-(4-alkylpiperazin-1-yl)phenyl group: a novel class of basic side chains for
      selective estrogen receptor modulators.
AB  - In the structure-activity relationships of spiro[indene-1,1'-indane] series, the
      4-(4-alkylpiperazin-1-yl)phenyl group was found to be functionally equipotent to
      the 4-(1-piperidinoethoxy)phenyl group, the most widely used basic side chain in
      selective estrogen receptor modulators.

PMID- 14643318
TI  - Novel histone deacetylase inhibitors: design, synthesis, enzyme inhibition, and
      binding mode study of SAHA-based non-hydroxamates.
AB  - In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a
      series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were
      designed and synthesized as (i). substrate (acetyl lysine) analogues (compounds 3
      7), (ii). analogues bearing various functional groups expected to chelate zinc
      ion (compounds 8-15), and (iii). analogues bearing nucleophilic functional groups
      which could bind covalently to HDACs (compounds 16-18). In this series,
      semicarbazide 8b and bromoacetamides 18b,c were found to be potent HDAC
      inhibitors for non-hydroxamates.

PMID- 14643319
TI  - Synthesis and analgesic activity of hydrochlorides and quaternary ammoniums of
      epibatidine incorporated with amino acid ester.
AB  - Hydrochloride derivatives 5a-c and quaternary ammonium derivatives 6a-c of
      epibatidine incorporated with amino acid ester were synthesized and evaluated for
      their in vivo analgesic activity and toxicity. Among all tested compounds,
      compound 6c has the most potent analgesic activity. The quaternary ammonium salts
      6a and 6c showed better analgesic activity than the corresponding hydrochlorides
      5a and 5c. Both 5a-c and 6a-c showed significantly lower toxicity than
      epibatidine itself.

PMID- 14643320
TI  - Catechol-substituted L-chicoric acid analogues as HIV integrase inhibitors.
AB  - HIV integrase catalyzes the integration of HIV DNA copy into the host cell DNA,
      which is essential for the production of progeny viruses. L-Chicoric acid and
      dicaffeoylquinic acids, isolated from plants, are well known potent inhibitors of
      HIV integrase. The common structural features of these inhibitors are caffeic
      acid derivatives connected to tartaric acid or quinic acid through ester bonds.
      In the present study, we have synthesized and tested the inhibitory activities of
      a new type of HIV IN inhibitors, which has catechol groups in place of caffeoyl
      groups in the structure of L-chicoric acid. Upon substitution of catechol groups
      at succinic acid, pyrrole-dicarboxylic acid, maleimide or maleic anhydride, the
      inhibitory activities (IC(50)=3.8-23.6 microM) were retained or remarkably
      increased when compared to parent compound L-chicoric acid (IC(50)=13.7 microM).

PMID- 14643321
TI  - Design and synthesis of statine-containing BACE inhibitors.
AB  - Utilizing structure-based techniques and solid-phase synthesis, statine-based
      tetrapeptide BACE inhibitors were designed and synthesized using a heptapeptide
      BACE transition-state mimetic, 1, as the starting point. Structure-activity
      relationship studies at the P(3), P(2), and P(2)' positions as well as the N
      terminal capping group on scaffold 5 led to the discovery of potent inhibitors
      27, 32, and 34 (IC(50) <100 nM). In addition, computational analysis and the X
      ray structure of BACE-inhibitor 38 are discussed.

PMID- 14643322
TI  - beta-alanine dipeptides as MC4R agonists.
AB  - beta-Alanine derivative 2 (IC(50)=16 nM) and related compounds were found to be
      potent MC4R agonists.

PMID- 14643323
TI  - New cerebrosides from Euphorbia peplis L.: antimicrobial activity evaluation.
AB  - The less polar fraction of the methanolic extract from the plant Euphorbia peplis
      L. exhibited interesting antifungal and antitubercular activity. A complex
      mixture of four glucocerebrosides was responsible for this activity. Two new
      cerebrosides were isolated for the first time from Euphorbiaceae, 4 was assigned
      as 1-O-(beta-D-glucopyranosyl)-(2S,3S,4E,8E)-2N-[(2'R)-2'-hydroxy-hexadecanoyl]-4
      (E), 8 (E)-octadecadiene-1,3-diol and 3 as the 1-O-(beta-D-glucopyranosyl)
      (2S,3S,4R,8Z)-2N-[(2'R)-2'-hydroxytetracosanoyl]-8 (Z)-octadecene-1,3,4-triol.
      The structures were determined on the basis of chemical and spectroscopic
      evidences. Mass spectrometry of dimethyl disulfide derivatives was useful for the
      determination of the double-bond positions in the long-chain bases.

PMID- 14643324
TI  - DAPI derivative: a fluorescent DNA dye that can be covalently attached to
      biomolecules.
AB  - The preparation of a DAPI (4',6-diamidino-2-phenylindole) derivative is
      described. The resulting derivative retains the fluorogenic property upon binding
      to double-stranded DNA. Its ability for bioconjugation through amide linkage is
      demonstrated.

PMID- 14643325
TI  - Successful shape-based virtual screening: the discovery of a potent inhibitor of
      the type I TGFbeta receptor kinase (TbetaRI).
AB  - We describe the discovery, using shape-based virtual screening, of a potent, ATP
      site-directed inhibitor of the TbetaRI kinase, an important and novel drug target
      for fibrosis and cancer. The first detailed report of a TbetaRI kinase small
      molecule co-complex confirms the predicted binding interactions of our small
      molecule inhibitor, which stabilizes the inactive kinase conformation. Our
      results validate shape-based screening as a powerful tool to discover useful
      leads against a new drug target.

PMID- 14643326
TI  - 4-methyl-1,2,4-triazol-3-yl heterocycle as an alternative to the 1-methylimidazol
      5-yl moiety in the farnesyltransferase inhibitor ZARNESTRA.
AB  - Replacement of the 1-methylimidazol-5-yl moiety in the farnesyltransferase
      inhibitor ZARNESTRA series by a 4-methyl-1,2,4-triazol-3-yl group gave us
      compounds with similar structure-activity relationship profiles showing that this
      triazole is potentially a good surrogate to imidazole for farnesyltransferase
      inhibition.

PMID- 14643327
TI  - Substituted azoloquinolines and -quinazolines as new potent farnesyl protein
      transferase inhibitors.
AB  - A series of (4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)azoloquinolines and
      -quinazolines was prepared. These compounds displayed potent Farnesyl Protein
      Transferase inhibitory activity and tetrazolo[1,5-a]quinazolines are promising
      agents for oral in vivo inhibition.

PMID- 14643328
TI  - Synthesis and antiviral evaluation of 3-hydroxy-2-methylpyridin-4-one
      dideoxynucleoside derivatives.
AB  - We describe the synthesis and the antiviral evaluation of novel alpha and beta
      dideoxynucleoside derivatives in which the base has been replaced by a 3-hydroxy
      2-methylpyridin-4-one. The syntheses were successfully achieved by the use of the
      standard Vorbruggen coupling conditions. Moderate activity of these compounds
      were found on herpes simplex virus (HSV) type 1 and type 2.

PMID- 14643329
TI  - 3D-QSAR studies on natural acetylcholinesterase inhibitors of Sarcococca saligna
      by comparative molecular field analysis (CoMFA).
AB  - We have derived a comprehensive structure-activity relationship (SAR) picture for
      a new series of natural acetylcholinesterase inhibitors isolated from Sarcococca
      saligna. A set of 32 previously isolated and tested pregnane-type steroidal
      alkaloids inhibitors were investigated with respect to their IC(50) values
      (pIC(50)) against the AChE enzyme in order to derive CoMFA models using atom
      based alignment. A highly significant CoMFA model was obtained with r(2) value of
      0.974. The q(2) (cross validation r(2)) value also confirms the statistical
      significance of our model.

PMID- 14643330
TI  - Heterocyclic aminopyrrolidine derivatives as melatoninergic agents.
AB  - A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as
      novel melatoninergic ligands. Binding affinity assays were performed on cloned
      human MT(1) and MT(2) receptors, stably expressed in NIH3T3 cells. Compound 16
      was identified as an orally bioavailable agonist at MT(1) and MT(2) melatonin
      receptors with low vasoconstrictive activity.

PMID- 14643331
TI  - Novel 3,4-dihydroquinolin-2(1H)-one inhibitors of human glycogen phosphorylase a.
AB  - The preparation of a series of substituted indoles coupled to six- and seven
      membered cyclic lactams is described and their role as human glycogen
      phosphorylase a inhibitors discussed. The SAR of the indole moiety and lactam
      ring are presented.

PMID- 14643332
TI  - Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural
      requirement for VR1 antagonistic effects.
AB  - A novel non-vanilloid VR1 antagonist consisting of a new vanilloid equivalent
      exhibits excellent analgesic effects as well as highly potent antagonistic
      activities in both capsaicin single channel and calcium uptake assays. In
      addition, the structural requirement for the vanilloid equivalent of the potent
      VR1 antagonist has also been elucidated.

PMID- 14643333
TI  - Antibacterial and antiproliferative activity of cationic fullerene derivatives.
AB  - We examined the antibacterial and antiproliferative activities of alkylated C(60)
      bis(N,N-dimethylpyrrolidinium iodide) derivatives. The fullerene derivatives
      inhibited bacteria and cancer cell growth effectively. However, the fullerene
      derivatives with a long alkyl chain did not show antibacterial activity.

PMID- 14643334
TI  - Synthesis and biological activity of novel 1beta-methylcarbapenems with
      oxyiminopyrrolidinylamide moiety.
AB  - The synthesis and antibacterial activity of novel 1beta-methylcarbapenems 1a-f
      bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are
      described. Most compounds exhibited comparable antibacterial activity to
      meropenem against a wide range of Gram-positive and Gram-negative organisms
      including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent
      and broad spectrum of antibacterial activity and similar stability to DHP-I to
      meropenem. Against clinical isolates of 40 Gram-negative bacterial species
      including MDR and ESBL-producing strains, the selected carbapenem 1a possessed
      excellent in vitro activity except for MDR P. aeruginosa, and was comparable in
      potency to meropenem.

PMID- 14643335
TI  - Stable analogues of geranylgeranyl diphosphate possessing improved geranylgeranyl
      versus farnesyl protein transferase inhibitory selectivity.
AB  - Phosphonoacetamido(oxy) groups have proven to be good mimics of the diphosphate
      portion in geranylgeranyl protein transferase I (GGTase I) inhibitors. The
      introduction of small alkyl groups (Me, Et) into the diphosphate mimic moiety
      caused a further decrease in collateral farnesyl protein transferase (FTase)
      inhibitory activity, thereby improving GGTase I over FTase selectivity.

PMID- 14643336
TI  - Design, synthesis and biological activity of novel dimethyl-[2-[6-substituted
      indol-1-yl]-ethyl]-amine as potent, selective, and orally-bioavailable 5-HT(1D)
      agonists.
AB  - A novel series of highly potent human 5-HT(1D) agonists, dimethyl-[2-[6
      substituted-indol-1-yl]-ethyl]-amine, was synthesized. Structure-activity
      relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6
      yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K(i)=2.4 nM) agonist
      at the human 5-HT(1D) receptor with good selectivity over the other serotonin
      receptor subtypes. This compound demonstrated favorable in vitro metabolic
      stability in human and rat liver microsomes and was found to be orally
      bioavailable in rats (F(po)=51%).

PMID- 14643337
TI  - Synthesis of non-immunosuppressive cyclophilin-Binding cyclosporin A derivatives
      as potential anti-HIV-1 drugs.
AB  - Original cyclosporin A (CsA) derivatives bearing various alkylthio side chains at
      the sarcosine residue 3 (R configuration) and for the most potent and selective
      compounds a 4'-hydroxyl group at the Me-Leucine residue 4 were prepared in one or
      two steps from commercially available CsA. The [2-(dimethyl or diethylamino)
      ethylthio-Sar](3)-[(4'-OH)MeLeu](4)-CsA derivatives 3k and 3l displayed potent in
      vitro anti-HIV-1 (IC(50) approximately 46 nM) and low immunosuppressive
      activities (IC(50)>or=1500 nM).

PMID- 14643338
TI  - Binding of beta-carbolines at 5-HT(2) serotonin receptors.
AB  - A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4
      tetrahydro-beta-carbolines was examined at 5-HT(2A) and 5-HT(2C) serotonin
      receptors. Whereas most of the methoxy-substituted derivatives typically
      displayed affinities similar to their unsubstituted parents, certain
      (particularly 8-substituted) bromo derivatives displayed enhanced affinity. A
      binding profile was obtained for selected beta-carbolines.

PMID- 14643339
TI  - 1-aryl-6,7-methylenedioxy-3H-quinazolin-4-ones as anticonvulsant agents.
AB  - A set of novel 1-aryl-6,7-methylenedioxy-3H-quinazolin-4-(thi)ones (3a-f) has
      been designed and screened as anticonvulsant agents in DBA/2 mice. The new
      compounds are provided with anticonvulsant properties comparable to those of GYKI
      52466. To clarify the mode of action, their affinity for the quinazolinone/2,3
      benzodiazepine site of the AMPA receptor complex has been assayed.

PMID- 14643340
TI  - Design and syntheses of melanocortin subtype-4 receptor agonists: evolution of
      the pyridazinone archetype.
AB  - The discovery and optimization of a new class of non-peptidyl, pyridazinone
      derived melanocortin subtype-4 receptor agonists is disclosed.

PMID- 14643341
TI  - Synthesis and anti-HIV properties of new water-soluble bis
      functionalized[60]fullerene derivatives.
AB  - A new series of bis-functionalized fullerene C(60) derivatives bearing two or
      more solubilizing chains have been evaluated for their activity against HIV-1 and
      HIV-2 strains. Some of the compounds show activity against HIV-1 type in the low
      micromolar range. The effect of the positions of the addends on the C(60) nucleus
      has been investigated, indicating that only trans-2 isomers possess promising
      activity. The presence of a quaternary pyrrolidinium nitrogen is essential to
      increase solubility.

PMID- 14643342
TI  - O-N intramolecular acyl migration strategy in water-soluble prodrugs of taxoids.
AB  - We synthesized a highly water-soluble canadensol prodrug 6 that formed canadensol
      3 by a simple pH-dependent chemical mechanism via the O-N intramolecular acyl
      migration of the isobutyryl group. This prodrug, a 2'-O-isobutyryl isoform of 3,
      has no additional functional auxiliaries released during the conversion to 3.
      This is a significant advantage in toxicology and medical economics, since the
      potential side effects of reported water-soluble auxiliaries and the use of
      detergent for solubilization can be avoided. The solubility of 6 was 2.26 mg mL(
      1) and only the parent drug 3 was released under physiological conditions
      (pH=7.4) while, in acidic medium, the release of 3 slowed until migration was
      completely obstructed at pH=2. In further consideration of this strategy, we
      elucidated the use of an 'O-N acyl-like' migration reaction of the Boc group in
      the design of a docetaxel prodrug. Both O-N migration and undesired hydrolysis of
      the Boc group occurred under physiological conditions, although no oxazolidinone
      formation was observed, suggesting the limitation of our water-soluble prodrug
      strategy to docetaxel.

PMID- 14643343
TI  - Potent anti-metastatic activity of dimeric sesquiterpene thioalkaloids from the
      rhizome of Nuphar pumilum.
AB  - The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar
      pumilum inhibited invasion of B16 melanoma cells across collagen-coated filters
      in vitro. Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group, 6
      hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, and 6
      hydroxythionuphlutine B, showed potent activity with IC(50) values of 0.029,
      0.087, and 0.36 microM, respectively, but dimeric sesquiterpene thioalkaloids
      lacking the 6-hydroxyl group (thiobinupharidine, neothiobinupharidine, syn
      thiobinupharidine sulfoxide, thionuphultine B beta-sulfoxide, and
      neothiobinupharidine beta-sulfoxide) and monomeric sesquiterpene alkaloids
      (nupharidine, deoxynupharidine, 7-epideoxynupharidine, and nupharolutine) showed
      weak activity. The alkaloid fraction (20 mg/kg/d, po) and the principal dimeric
      sesquiterpene thioalkaloid 6-hydroxythiobinupharidine (5 mg/kg/d, po)
      significantly inhibited lung tumor formation by more than 90% 10 days after
      injection of B16 melanoma cells in mice.

PMID- 14643344
TI  - Synthesis of new 3-arylisoquinolinamines: effect on topoisomerase I inhibition
      and cytotoxicity.
AB  - To investigate the structure-activity relationships of 3-arylisoquinolines,
      diverse substituted 3-aryisoquinolinamines were synthesized and tested in vitro
      antitumor activity against four tumor cell lines. Some of the compounds showed
      potent topoisomerase I inhibitory activity. Docking study of 7d with
      topoisomerase I-DNA complex was also performed.

PMID- 14643345
TI  - Synthesis and evaluation of optically pure dioxolanes as inhibitors of hepatitis
      C virus RNA replication.
AB  - A series of optically pure 1,3-dioxolane nucleoside mimics was synthesized by a
      synthetic route that allowed incorporation of a 5R-methyl substituent from
      commercially available starting materials. The pyrrolo[2,3-d]pyrimidine
      heterocycle was chosen as a substitute for the purine derivative. Coupling of the
      pyrrolo[2,3-d]pyrimidine and the dioxolane was performed under solid-liquid phase
      transfer conditions. The ability to inhibit HCV RNA replication was assessed in a
      cell based subgenomic replicon assay. None of the described compounds displayed
      significant anti-HCV activity.

PMID- 14643346
TI  - trans-3,4-dimethyl-4-(3-carboxamidophenyl)piperidines: a novel class of micro
      selective opioid antagonists.
AB  - trans-3,4-Dimethyl-4-(3-carboxamidophenyl)piperidines constitute a novel class of
      micro opioid receptor antagonists. The CONH(2) group was found to be an effective
      isostere of the phenolic OH moiety. Structure-activity relationships at the
      piperidine nitrogen position led to the identification of several ligands
      displaying high affinity toward the cloned human micro opioid receptors, good
      selectivity micro/delta, micro/kappa, and potent in vitro antagonist activity.

PMID- 14643347
TI  - Ureas of 5-aminopyrazole and 2-aminothiazole inhibit growth of gram-positive
      bacteria.
AB  - Ureas of 5-aminopyrazole and 2-aminothiazole emerged as lead compounds from a
      high-throughput screen assaying the growth of Staphylococcus aureus. Structure
      activity relationships were developed for each compound series. Several compounds
      were also tested for activity against drug resistant strains of S. aureus in
      vivo.

PMID- 14643349
TI  - 1,3-dihydrobenzo[c]furan nucleoside analogues: additional studies of the thymine
      derivative.
AB  - The detailed study of the 1,3-dihydrobenzo[c]furan derivative of thymine is
      reported. The lack of anti-HIV activity of this compound in cell culture
      experiments is shown to be related to the inability of the corresponding 5'
      triphosphate derivative to interact efficiently with the reverse transcriptase.

PMID- 14643348
TI  - Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1H
      imidazol-2-yl)-1H-indoles, a systematic SAR evaluation. Part 2.
AB  - We have systematically explored the structure-activity relationship (SAR) for a
      series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a
      serine protease responsible for the degradation of cholecystokinin-8 (CCK-8).
      This SAR evaluation of the core structure 2 suggest a fairly restrictive
      pharmacophore for such related structures, but has yielded a limited set of
      compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC(50)
      4-11 nM).

PMID- 14643350
TI  - Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake.
AB  - A series of naphthalenyloxy-arylpropylamines have been prepared and are
      demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One
      member of this series, duloxetine (Cymbalta) has proven to be effective in
      clinical trials for the treatment of depression.

PMID- 14643351
TI  - Conicamin, a novel histamine antagonist from the mediterranean tunicate Aplidium
      conicum.
AB  - In addition to the known 6-bromo-hypaphorine (2) and plakohypaphorine-A (3), the
      methanol extract of the Mediterranean tunicate Aplidium conicum was shown to
      contain conicamin, a novel indole alkaloid having histamine-antagonistic activity
      which structure was determined to be 1 on the basis of the spectral data.

PMID- 14643352
TI  - Exploration of the bicyclo[3.3.1]nonane system as a template for the development
      of new ligands for the estrogen receptor.
AB  - Three novel structural motifs based on a bicyclo [3.3.1]nonane template were
      examined as new ligands for estrogen receptor (ER). Type III compounds emerged as
      the most promising leads for developing high-affinity ER ligands, but they showed
      little selectivity for either ER subtype. Type II compounds, on the other hand,
      despite their lower affinity, exhibited significant ERbeta binding selectivity.

PMID- 14643353
TI  - Novel mechanism of inhibiting beta-lactamases by sulfonylation using beta
      sultams.
AB  - Beta-sultams are the sulfonyl analogues of beta-lactams and N-acyl beta-sultams
      are novel inactivators of the class C beta-lactamase of Enterobacter cloacae P99.
      The rates of inactivation show a similar pH-rate dependence as that exhibited by
      the beta-lactam antibiotics and with ESIMS data it is suggested that beta-sultams
      sulfonylate the active site serine residue to form a sulfonate ester.

PMID- 14643354
TI  - Microbial transformation of baccatin VI and 1beta-hydroxy baccatin I by
      Aspergillus niger.
AB  - The biotransformation of baccatin VI (1) and 1beta-hydroxybaccatin I (2) with the
      filamentous fungus Aspergillus niger produced four new taxane diterpenoids
      taxumairol S(1) (3), taxumairol T(1) (4) and taxumairol S (5), taxumairol T (6),
      respectively. 1beta-Dehydroxybaccatin VI (7) remained unreacted under the same
      condition.

PMID- 14643355
TI  - N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: the first orexin-2 receptor
      selective non-peptidic antagonist.
AB  - The identification of potent and selective orexin-2 receptor (OX(2)R) antagonists
      is described based on the modification of N-acyl 6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline analogue 1, recently discovered during high throughput
      screening (HTS). Substitution of an acyl group in 1 with tert-Leucine (tert-Leu),
      and introduction of a 4-pyridylmethyl substituent onto the amino function of tert
      Leu improved compound potency, selectivity, and water solubility. Thus, compound
      29 is a promising tool to investigate the role of orexin-2 receptors.

PMID- 14643356
TI  - Structure-activity relationships of indole cytosolic phospholipase A(2)alpha
      inhibitors: substrate mimetics.
AB  - An SAR effort focused on generating cPLA(2)alpha inhibitors using a substrate
      mimetic approach is reported. Indole inhibitors of cPLA(2)alpha with promising
      pharmacokinetic parameters that were active in both an isolated enzyme assay and
      in cell-based assays were discovered. Modeling these compounds into the
      cPLA(2)alpha structure validated the assumptions made at the start of the SAR
      effort.

PMID- 14643357
TI  - Design and pharmacology of peptoids and peptide-peptoid hybrids based on the
      melanocortin agonists core tetrapeptide sequence.
AB  - A series of N-substituted glycine oligomers (peptoids) and peptide-peptoid
      hybrids were synthesized based on the Ac-His-Phe-Arg-Trp-NH(2) tetrapeptide
      template. The compounds were pharmacologically characterized at the mouse
      melanocortin receptors (MC1R, MC3R-MC5R) for agonist activity.

PMID- 14643358
TI  - Novel bicyclic furanopyrimidines with dual anti-VZV and -HCMV activity.
AB  - Several novel bicyclic furanopyrimidine deoxy nucleosides have been designed,
      prepared and evaluated as anti-Varicella Zoster Virus agents. The compounds have
      long ether side chains. Uniquely amongst compounds of this family to date the
      present agents show dual anti- (VZV) and human cytomegalovirus (HCMV) activity.
      The lead compounds inhibit VZV at 10 nM and HCMV at 5 microM.

PMID- 14643359
TI  - An unnatural hydrophobic base, 4-propynylpyrrole-2-carbaldehyde, as an efficient
      pairing partner of 9-methylimidazo[(4,5)-b]pyridine.
AB  - To develop unnatural base pairs that function in replication, we designed 4
      propynylpyrrole-2-carbaldehyde (designated as Pa') and synthesized the nucleoside
      derivatives of Pa'. The base pairing of Pa' with the partner, 9
      methylimidazo[(4,5)-b]pyridine (Q), was compared to that of pyrrole-2
      carbaldehyde (Pa), which was previously developed as a specific pairing partner
      of Q. The thermal stability of a DNA duplex containing the Q-Pa' pair and the
      incorporation efficiency of the Pa' substrate (dPa'TP) into DNA opposite Q by the
      Klenow fragment of Escherichia coli DNA polymerase I were improved, in comparison
      with those of the Q-Pa pair. These improvements result from the increased
      hydrophobicity and stacking stability of Pa' by the introduction of the propynyl
      group to Pa, providing valuable information for the further development of
      unnatural base pairs toward the expansion of the genetic alphabet.

PMID- 14643361
TI  - The downside of categories.
AB  - One of the primary uses of categories is to draw inferences about novel objects
      based on their category membership. In a recent study, Lagnado and Shanks show
      that people make different inferences about an object depending on whether they
      first categorize the object at a general or specific level. Indeed, their
      inference changes even though they have been given no information about the
      object. This finding reveals limitations of category-based induction.

PMID- 14643362
TI  - Superior parietal cortices and varieties of mental rotation.
AB  - Mental rotation is the most distinctly specialized operation of the imagination,
      one characterized precisely enough psychophysically for parametric study, thereby
      making it an optimal prospect for isolating and modeling its neural mechanisms.
      New human brain mapping studies using direct cortical stimulation and repetitive
      transcranial magnetic stimulation isolate an area in right superior parietal
      cortex that appears to be crucial for the mental rotation of objects, but not to
      the mental rotation of one's body.

PMID- 14643363
TI  - Neural representations in human spatial memory.
AB  - Ekstrom et al. report the responses of single neurons recorded from the brains of
      human subjects performing a spatial navigation task in virtual reality. They
      found cells encoding the subject's current location, view and destination. These
      data, and related findings in animals, directly reveal some of the
      representations underlying spatial cognition. They highlight the potential for
      cognitive psychology and systems neuroscience to combine to provide a neuronal
      level understanding of human behaviour.

PMID- 14643367
TI  - Just another view.

PMID- 14643368
TI  - Shared representations between self and other: a social cognitive neuroscience
      view.
AB  - The abilities to identify with others and to distinguish between self and other
      play a pivotal role in intersubjective transactions. Here, we marshall evidence
      from developmental science, social psychology and neuroscience (including
      clinical neuropsychology) that support the view of a common representation
      network (both at the computational and neural levels) between self and other.
      However, sharedness does not mean identicality, otherwise representations of self
      and others would completely overlap, and lead to confusion. We argue that self
      awareness and agency are integral components for navigating within these shared
      representations. We suggest that within this shared neural network the inferior
      parietal cortex and the prefrontal cortex in the right hemisphere play a special
      role in interpersonal awareness.

PMID- 14643369
TI  - Why theories about developmental dyslexia require developmental designs.
AB  - This article examines the importance of developmental designs in dyslexia
      research using a neuroconstructivist framework. According to neuroconstructivism,
      the lowest level of impairment should be identified as early as possible, and
      developmental effects on higher-level cognition examined longitudinally. A number
      of recent studies proposing candidate low-level impairments have not used such
      developmental designs. The role of normal variation in postulated causal factors
      on development is ignored, inadequate control groups are used, and the nature and
      timing of environmental inputs are not measured, even though reading is taught
      systematically and both reading acquisition and dyslexia vary with orthography.
      It is suggested here that only a phonological deficit arising from low-level
      auditory processing problems meets the criteria for a neuroconstructivist
      approach.

PMID- 14643370
TI  - Sensory substitution and the human-machine interface.
AB  - Recent advances in the instrumentation technology of sensory substitution have
      presented new opportunities to develop systems for compensation of sensory loss.
      In sensory substitution (e.g. of sight or vestibular function), information from
      an artificial receptor is coupled to the brain via a human-machine interface. The
      brain is able to use this information in place of that usually transmitted from
      an intact sense organ. Both auditory and tactile systems show promise for
      practical sensory substitution interface sites. This research provides
      experimental tools for examining brain plasticity and has implications for
      perceptual and cognition studies more generally.

PMID- 14643371
TI  - Working memory capacity and its relation to general intelligence.
AB  - Early investigations of working memory capacity (WMC) and reasoning ability
      suggested that WMC might be the basis of Spearman's g. However, recent work has
      uncovered details about the basic processes involved in working memory tasks,
      which has resulted in a more principled approach to task development. As a
      result, claims now being made about the relation between WMC and g are more
      cautious. A review of the recent research reveals that WMC and g are indeed
      highly related, but not identical. Furthermore, WM span tasks involve an
      executive-control mechanism that is recruited to combat interference and this
      ability is mediated by portions of the prefrontal cortex. More combined
      experimental-differential research is needed to understand better the basis of
      the WMC-g relation.

PMID- 14643372
TI  - Synchronous neural oscillations and cognitive processes.
AB  - The central problem for cognitive neuroscience is to describe how cognitive
      processes arise from brain processes. This review summarizes the recent evidence
      that synchronous neural oscillations reveal much about the origin and nature of
      cognitive processes such as memory, attention and consciousness. Memory processes
      are most closely related to theta and gamma rhythms, whereas attention seems
      closely associated with alpha and gamma rhythms. Conscious awareness may arise
      from synchronous neural oscillations occurring globally throughout the brain
      rather than from the locally synchronous oscillations that occur when a sensory
      area encodes a stimulus. These associations between the dynamics of the brain and
      cognitive processes indicate progress towards a unified theory of brain and
      cognition.

PMID- 14643373
TI  - Proceedings of a symposium on molecular and cellular basis of synaptic loss and
      dysfunction in Alzheimer's disease. Orlando, Florida, USA, 2002.

PMID- 14643374
TI  - Synaptic slaughter in Alzheimer's disease.
AB  - Synaptic loss is currently established as the best neurobiological correlate of
      the cognitive deficits of Alzheimer's disease (AD) [Ann. Neurol. 27 (1990) 457;
      Ann. Neurol. 30 (1991) 572]. We provide evidence that still living neurons lose
      synapses in AD, in addition to the synapse loss due to death of neurons. We also
      provide evidence indicating that in addition to loss of synapses, synaptic
      function is also affected in AD by decrements in transcript species related to
      synaptic vesicle trafficking.

PMID- 14643375
TI  - Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies.
AB  - Morphologic studies of the neuropathology in Alzheimer's disease (AD) have
      demonstrated significant loss of synaptic connectivity in many regions of the
      neocortex and hippocampus. The strongest correlation with cognitive decline in AD
      is with the synaptic density. This article discusses the ultrastructural studies
      that have documented changes in synaptic numbers in many areas of association
      cortex and in the hippocampal dentate gyrus molecular layer. Changes in the
      synaptic complex are discussed as a possible compensatory mechanism in response
      to synapse loss and a model is proposed to help relate the significance of these
      synaptic changes. Comparisons are made between results observed with
      ultrastructural technique and those utilizing immunohistochemistry to assess
      changes in synaptic pathology. Possible reasons underlying the synaptic
      neuropathology are discussed.

PMID- 14643376
TI  - Pathology of presynaptic proteins in Alzheimer's disease: more than simple loss
      of terminals.
AB  - Synaptic pathology is receiving increased attention in the study of the
      pathophysiology of Alzheimer's disease. A review of the literature on synaptic
      pathology in Alzheimer's disease was undertaken, focused on five areas. First,
      concerning the molecular substrates of presynaptic terminal changes, not all
      proteins are equally affected. Second, all brain regions in Alzheimer's disease
      do not show equivalent presynaptic protein pathology, hippocampus tended to be
      most affected. Third, relationships between presynaptic and neurofibrillary
      tangle pathology tended to be stronger than relationships with plaques. Fourth,
      broadly speaking, more severe cognitive impairment was associated with more
      severe presynaptic pathology. Finally, the relationship of presynaptic pathology
      and stage of illness appeared complex, with some reports of increased presynaptic
      proteins in earlier phases of illness, but consistent decreases in later phases.
      Detailed studies of presynaptic pathology in transgenic mouse models related to
      Alzheimer's disease may provide important insights concerning these observations.

PMID- 14643377
TI  - Amyloid deposition precedes tangle formation in a triple transgenic model of
      Alzheimer's disease.
AB  - Amyloid-beta (Abeta) containing plaques and tau-laden neurofibrillary tangles are
      the defining neuropathological features of Alzheimer's disease (AD). To better
      mimic this neuropathology, we generated a novel triple transgenic model of AD
      (3xTg-AD) harboring three mutant genes: beta-amyloid precursor protein
      (betaAPPSwe), presenilin-1 (PS1M146V), and tauP301L. The 3xTg-AD mice
      progressively develop Abeta and tau pathology, with a temporal- and regional
      specific profile that closely mimics their development in the human AD brain. We
      find that Abeta deposits initiate in the cortex and progress to the hippocampus
      with aging, whereas tau pathology is first apparent in the hippocampus and then
      progresses to the cortex. Despite equivalent overexpression of the human betaAPP
      and human tau transgenes, Abeta deposition develops prior to the tangle
      pathology, consistent with the amyloid cascade hypothesis. As these 3xTg-AD mice
      phenocopy critical aspects of AD neuropathology, this model will be useful in pre
      clinical intervention trials, particularly because the efficacy of anti-AD
      compounds in mitigating the neurodegenerative effects mediated by both signature
      lesions can be evaluated.

PMID- 14643378
TI  - Use of YFP to study amyloid-beta associated neurite alterations in live brain
      slices.
AB  - Neuritic plaques are one of the defining neuropathological features of
      Alzheimer's disease (AD). These structures are composed of a buildup of fibrils
      of the amyloid-beta (Abeta) peptide (amyloid) surrounded by activated glial cells
      and degenerating nerve processes (dystrophic neurites). To study neuritic plaques
      and possible abnormalities associated with dendrites, axons, and synaptic
      structures, we have developed an acute slice preparation model using PDAPP,
      yellow fluorescent protein (YFP) double transgenic mice (a mouse model with AD
      like pathology that stably expresses YFP in a subset of neurons in the brain).
      With laser scanning confocal microscopy, we have imaged living brain slices from
      PDAPP, YFP double transgenic mice as old as 20 months and have been able to
      visualize axons, dendrites, dendritic spines, and dystrophic neurites for many
      hours. Our initial studies suggest that dystrophic axons and dendrites within
      neuritic plaques are fairly stable structures in the absence of exogenous
      perturbations. This acute slice preparation model should prove to be a useful
      tool to explore the pathophysiology of Abeta-related axonal, dendritic, and
      synaptic dysfunction.

PMID- 14643379
TI  - Clogging of axons by tau, inhibition of axonal traffic and starvation of
      synapses.
AB  - Loss of synapses and dying back of axons are considered early events in brain
      degeneration during Alzheimer's disease. This is accompanied by an aberrant
      behavior of the microtubule-associated protein tau (hyperphosphorylation,
      aggregation). Since microtubules are the tracks for axonal transport, we are
      testing the hypothesis that tau plays a role in the malfunctioning of transport.
      Experiments with various neuronal and non-neuronal cells show that tau is capable
      of reducing net anterograde transport of vesicles and cell organelles by blocking
      the microtubule tracks. Thus, a misregulation of tau could cause the starvation
      of synapses and enhanced oxidative stress, long before tau detaches from
      microtubules and aggregates into Alzheimer neurofibrillary tangles. In
      particular, the transport of amyloid precursor protein is retarded when tau is
      elevated, suggesting a possible link between the two key proteins that show
      abnormal behavior in Alzheimer's disease.

PMID- 14643380
TI  - GSK-3 dependent phosphoepitopes recognized by PHF-1 and AT-8 antibodies are
      present in different tau isoforms.
AB  - It is widely known that the tau protein that forms the aggregates found in
      tauopathies like Alzheimer's disease (AD) is hyperphosphorylated. Many of the
      sites that are hyperphosphorylated in AD can also be found phosphorylated in non
      pathological control brains, although to a lesser extend. Among the different
      kinases that are able to phosphorylate tau in these sites, GSK-3 has emerged as a
      key effector of AD pathogenesis in view of its interaction with many of the
      proteins involved in the ethiology of AD. In this work, we have tested if control
      samples show only a decrease in the amount of phosphorylated tau molecules, or if
      the phosphorylation at different sites occurs in different tau isoforms, whereas
      in the pathological situation a single tau isoform is modified simultaneously at
      the different sites. Our results indicate that the second possibility takes place
      and that the differences in the phosphorylation of different tau isoforms could
      be due to a different subcellular distribution of these different tau isoforms in
      a neuron.

PMID- 14643381
TI  - Age-related regulation of dendritic endocytosis associated with altered clathrin
      dynamics.
AB  - The protein composition of the neuronal plasma membrane is regulated by clathrin
      mediated endocytosis and changes drastically over the neuronal lifespan. Here, we
      utilize the transition out of the period of early postnatal growth as a model
      system to study age-related changes in endocytosis. Previously, we have found
      that the dynamic behavior of endocytic clathrin coats in dendrites changes during
      this period, and that clathrin coat lifetime increases in older neurons. In this
      study, we examine endocytosis in neuronal dendrites by measuring transferrin (Tf)
      uptake, and find that it is markedly reduced in older neurons in culture. This
      decrease was not due to a reduction in transferrin receptor protein levels, nor
      to a decrease in the expression of endocytic proteins. However, imaging of
      endocytosis in living dendrites demonstrated that cargo transport through
      clathrin-coated pits was slower during internalization. Thus, endocytic function
      in dendrites is altered in older neurons, suggesting that as neurons age, protein
      trafficking mechanisms are controlled to complement maturational requirements.

PMID- 14643382
TI  - Mechanisms of translational control in dendrites.
AB  - Synaptogenesis and synaptic plasticity demonstrate the ability of neurons to
      mature and respond to various stimuli. Both of these events require protein
      synthesis, in particular, localized translation within dendrites. Dendrites
      localize specific mRNAs in proximity to dendritic spines and have the capacity to
      actively translate these mRNAs within various 'hotspots' in the dendritic space.
      Rates of dendritic translation are stimulated and inhibited by various agents,
      suggesting that several signaling pathways that modulate localized protein
      synthesis may exist within the dendrite. This review will cover several suggested
      pathways for regulation of dendritic translation and propose a correlation
      between deregulated dendritic translation and disease.

PMID- 14643383
TI  - Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington
      disease.
AB  - N-Methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity has been proposed
      to play a role in Huntington disease (HD), caused by expansion of a polyglutamine
      tract in the protein huntingtin. HD is characterized by selective
      neurodegeneration most severely affecting striatal medium-sized spiny projection
      neurons (MSNs), where expression of the NMDAR subunit NR2B is increased relative
      to other NR2 subunits. Here, we review our data that NR2B-type NMDAR currents are
      selectively potentiated by mutant huntingtin in transfected non-neuronal cells
      and acutely dissociated striatal MSNs from the YAC72 transgenic mouse model of
      HD. As well, we report increased striatal MSN NMDAR-mediated synaptic currents in
      corticostriatal slice recordings from YAC72 compared with wild-type mice. This
      effect was associated with a larger NMDAR- to AMPAR-mediated current ratio,
      suggesting specific potentiation of postsynaptic NMDARs. Enhanced NMDAR current
      likely involves increased surface receptor numbers or activity, since we observed
      no differences between genotypes in striatal NR2B expression. Potentiation of
      NR2B-containing NMDAR current in striatal MSNs expressing mutant huntingtin may
      help explain the exquisite vulnerability of these neurons to degeneration in HD.

PMID- 14643384
TI  - NMDA receptor regulation of nNOS phosphorylation and induction of neuron death.
AB  - Stimulation of NMDA receptors activates neuronal nitric oxide synthase (nNOS) and
      the production of nitric oxide (NO). Dephosphorylation of nNOS increases nNOS
      enzymatic activity. We have examined the regulation of nNOS phosphorylation in
      rat cortical neurons following NMDA receptor activation. We show that nNOS is
      constitutively phosphorylated and that NMDA receptor activation decreases the
      level of nNOS phosphorylation by a mechanism that is blocked specifically by NMDA
      receptor antagonists and inhibitors of the Ca2+-regulated phosphatases
      calcineurin and PP1/PP2A. Using quantitative digital microscopy, we show that
      NMDA receptor activation induces the accumulation of nitrotyrosine, a measure of
      nNOS activity, and TdT-mediated fluorescein-dUTP nick end labeling (TUNEL)
      positivity, a measure of cell death. A calcineurin inhibitor blocked the increase
      in both TUNEL and nitrotyrosine positivity. Notably, TUNEL was increased in those
      neurons that were most strongly positive for nitrotyrosine. We conclude that NMDA
      receptor activation induces death of neurons by a cell autonomous pathway
      involving nNOS dephosphorylation by a calcineurin-dependent mechanism.

PMID- 14643385
TI  - Neurotrophin secretory pathways and synaptic plasticity.
AB  - Neurotrophins and synaptic activity work in conjunction during the process of
      synaptic plasticity. Both are required to stabilize new synaptic structures and
      the loss of either can lead to cognitive impairments, as new information cannot
      be stored efficiently or later recalled. Neurotrophins are becoming recognized as
      mediators of activity-dependent plasticity. The synthesis and release of
      neurotrophins follow neurosecretory pathways. They are synthesized as immature,
      pro-neurotrophin molecules, processed, and then mature forms are secreted. These
      then activate distinct signal tranduction pathways that modify the synapse. High
      frequency stimulation is known to induce long-term potentiation (LTP) and
      synaptic enhancement, however, the stability of these changes requires a bi
      directional communication between the pre- and post-synaptic terminals and
      neurotrophins can function in such a capacity. The NGFXAT somatic mosaic murine
      model demonstrated how neurotrophin and active learning induces a robust synaptic
      reorganization. Synaptic dysfunction decreases efficient neurotransmission or
      neurotrophin production and then precedes overt neurodegeneration. The study of
      synaptic dysfunction and neurotrophin actions with respect to activity will lead
      to future therapeutic interventions of age-related dementias.

PMID- 14643386
TI  - Decreased plasma membrane expression of striatal dopamine transporter in aging.
AB  - Aging in rodents, monkeys, and man is correlated with a reduction in dopamine
      transporter (DAT) ligand binding and DAT function. Using Western blot techniques,
      we investigated whether the source of these age-related changes in DAT was
      correlated with decreases in DAT protein levels in the striatum, substantia nigra
      (SN), nucleus accumbens (NAc), and ventral tegmental area (VTA) of 6, 18, and 24
      month-old male Fischer 344 rats. The relative levels of tyrosine hydroxylase (TH)
      were also determined in each region. In the striatum, we also assessed [3H]-DA
      uptake and DAT plasma membrane expression using a membrane-impermeant biotin
      analog in crude synaptosomes prepared from these age groups. There was no
      significant age-related difference in DAT immunoreactivity per total protein or
      per total TH in striatum, NAc, SN, or VTA. Significant age-related changes in TH
      were only seen in the VTA of the 24-month-old rats (approximately 60% decrease).
      However, [3H]-DA uptake and DAT protein recovered in the biotinylated fraction in
      24-month-old rats were significantly decreased (approximately 30%) compared to 6
      month-old animals in the striatal synaptosomes. These data suggest that age
      related decreases in striatal DAT function and ligand binding are related to a
      decrease in plasma membrane expression of DAT and not a decrease in the steady
      state levels of DAT protein or loss of dopaminergic neuropil.

PMID- 14643387
TI  - Nucleated red blood cell counts: not associated with brain injury or outcome.
AB  - The objective was to determine whether an elevated nucleated red blood cell count
      at birth after perinatal depression is associated with brain injury as measured
      by (1) proton magnetic resonance spectroscopy and (2) abnormal neurodevelopmental
      outcome at 30 months of age. The nucleated red blood cell counts from the first
      24 hours of life were statistically analyzed in 33 term infants enrolled in a
      prospective study of the value of magnetic resonance imaging for the
      determination of neurodevelopmental outcome after perinatal depression. Nucleated
      red blood cell counts were elevated in 13/33 (39%). Abnormal outcome (19/33, 54%)
      was associated with Score for Neonatal Acute Physiology-Perinatal Extension (P =
      0.04), decreased N-acetylaspartate to choline ratio in the basal ganglia (P =
      0.009), and increased lactate to choline ratio in the basal ganglia (P = 0.02),
      but not with cord pH, Apgar score, or nucleated red blood cell value. In a
      logistic regression model, increasing nucleated red blood cell counts did not
      increase the odds of an abnormal outcome at 30 months of age (OR 1.02, P = 0.17).
      In a population of neonates with perinatal depression, the nucleated red blood
      cell count at birth does not correlate with magnetic resonance spectroscopy or 30
      month neurodevelopmental outcome. The nucleated red blood cell count should not
      be used as a surrogate marker for subsequent brain injury.

PMID- 14643388
TI  - New GAA mutations in Japanese patients with GSDII (Pompe disease).
AB  - Glycogen storage disease type II (Pompe disease) is inherited by autosomal
      recessive transmission and caused by a deficiency of acid alpha-glucosidase
      (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen.
      The GAA gene, responsible for this disease, has been mapped to chromosome 17q25.2
      25.3. To date, more than 70 disease-causing mutations have been identified. In
      this study, we present four mutations found in three Japanese patients with the
      juvenile form of glycogen storage disease type II; three of these mutations were
      new (R224W, S619R, and R660H). The pathogenicity of these new mutations was
      verified by the loss of function of the mutant enzymes expressed in COS cells.

PMID- 14643389
TI  - Neonatal bacterial meningitis in southern Taiwan.
AB  - To determine the epidemiologic trends, prognostic factors, and therapeutic
      results of neonatal bacterial meningitis, 60 neonatal patients with culture
      proven neonatal bacterial meningitis were enrolled in this study. To compare
      changes over time, the appearance of disease among the patients was divided into
      two equal periods (1986-1993 and 1994-2001). Group B streptococci were the most
      common causative pathogens, accounting for approximately 32% of the episodes.
      Escherichia coli, the next most common pathogen, was more frequently observed in
      the second period. Seventy-seven percent of gram-negative bacilli isolates were
      resistant to ampicillin. Moreover, oxacillin-resistant Staphylococcus and
      ampicillin-resistant group B streptococci strains occurred in the second periods
      as late-onset neonatal bacterial meningitis. The overall mortality rates for the
      first and second study period were 17% and 8%, respectively. However, if
      individuals with poor outcomes were taken into account, 38% of patients were
      considered treatment failures. Significant prognostic factors included the
      presence of seizures, thrombocytopenia, and high cerebrospinal fluid protein and
      low cerebrospinal fluid glucose concentration. Although the mortality rate was
      significantly reduced in the second period, there has been increasing incidence
      of the emergence of resistant strains presenting a therapeutic challenge. The
      presentation in neonatal bacterial meningitis might be nonspecific, and blood
      culture results were negative in 45% of the episodes. Early diagnosis, choice of
      appropriate antibiotics, and correction of metabolic derangement are essential to
      improving outcomes.

PMID- 14643390
TI  - The use of enoxaparin in children with acute, nonhemorrhagic ischemic stroke.
AB  - The use of low-molecular-weight heparin offers multiple advantages over
      unfractionated heparins in pediatric patients with acute ischemic stroke. The
      safety and efficacy of low-molecular-weight heparin have been demonstrated in
      adults, but less is known about their use in children. This study reviews
      retrospectively the use of low-molecular-weight heparin in children with acute,
      ischemic, nonhemorrhagic strokes. A database search was used to locate all
      children who experienced an ischemic stroke between July 1991 and January 2001
      and who were subsequently treated with low-molecular-weight heparin. Eight
      children were identified (aged 37 months to 17 years; median age, 133 months) who
      were treated with the low-molecular-weight heparin enoxaparin. Enoxaparin was
      used in one case as the sole treatment, in six cases as a bridge to oral
      anticoagulant therapy with warfarin, and in one case as a replacement treatment
      after several days of warfarin therapy. The median duration of treatment with
      enoxaparin was 4 days. During this period, no major bleeding complications were
      observed, and no new thrombi or extensions of thrombi occurred. One patient did
      experience mild oozing at an intravenous site, and another experienced an episode
      of epistaxis. Enoxaparin was discontinued in one patient because of discomfort
      associated with the subcutaneous injections. Although the number of patients was
      limited, it appears that enoxaparin is a safe and efficacious alternative to the
      use of unfractionated heparin in children with acute, nonhemorrhagic ischemic
      stroke.

PMID- 14643391
TI  - The use of botulinum toxin type A treatment in children with spasticity.
AB  - The current modalities in managing spastic children have some limitations; thus,
      alternative therapeutic agents are in need. The purpose of this study is to
      investigate whether intramuscular botulinum toxin type A administration may be an
      alternative agent in the treatment of children with cerebral palsy. Eighteen
      children who were aged between 3 and 17 years and manifested cerebral palsy were
      administered intramuscular botulinum toxin type A with a total dose of 6 U/kg
      body weight. Outcome measurements were determined with four methods, including
      Ashworth Spasticity Scale, standardized videotape assessments, observational gait
      analysis, and walking velocity. Ashworth Spasticity Scale and videotape
      assessments were statistically significant before and after treatment in all
      muscles (P < 0.001). The best improvement in video gait analysis was evident at
      week 8. The botulinum toxin type A injections yielded an improved walking
      velocity at all visits. The observational gait analysis and walking velocity
      demonstrated an improvement after treatment in the gastrocnemius-injected group
      (P < 0.001). In conclusion, intramuscular botulinum toxin type A administration
      may be effective in children with cerebral palsy, especially at week 4 and when
      injected in gastrocnemius.

PMID- 14643392
TI  - Pediatric epilepsy surgery at the University of Alberta: 1988-2000.
AB  - Epilepsy surgery is considered a treatment option for patients with intractable
      seizures. Relatively few studies of efficacy, safety, and long-term outcome are
      available for the pediatric age group. This study describes a 12-year experience
      with pediatric epilepsy surgery at the University of Alberta. Records of
      pediatric epilepsy surgery patients admitted to the Comprehensive Epilepsy
      Program at the University of Alberta between 1988 and 2000 were reviewed. All
      patients received preoperative and postoperative clinical evaluation, seizure
      charts, testing of drug levels, electroencephalogram, computed
      tomography/magnetic resonance imaging, neuropsychologic testing, and long-term
      video electroencephalogram monitoring. The patients were reassessed after surgery
      at 6 weeks, 6 months, and 1 year and then yearly. The duration of follow-up was 1
      year to 12 years. Forty-two patients underwent temporal lobectomies; 35,
      extratemporal resection. The age at surgery ranged from 6 months to 16 years.
      Thirty-two (76%) of temporal lobe patients became seizure-free (Engel Class I) vs
      24 (68%) for the extratemporal group (Engel Class I). One patient (2%) in the
      temporal group had an Engel Class II outcome and one patient (3%) in the
      extratemporal group had the same Engel Class II outcome. Three patients (4%)
      manifested postoperative complications, and there were no deaths. Patients
      reported improvement in cognitive abilities, behavior, and quality of life after
      the surgery. Epilepsy surgery in children is effective and safe. Many children
      are seizure-free after the operation and remain so, although the results of
      temporal lobectomy are better than for extratemporal resections. There are few
      complications, and children often have an improved quality of life.

PMID- 14643393
TI  - Cytokine profile in cerebrospinal fluid of children with echovirus type 4
      meningitis.
AB  - Cytokines play a role in meningeal inflammation and leukocyte recruitment.
      Research has demonstrated that levels of different cytokines are elevated in
      aseptic and viral meningitis. Unfortunately, previous data were confounded by the
      inclusion of multiple viral agents as a study group. The aims of the study were
      to determine the cerebrospinal fluid concentrations of various cytokines in an
      outbreak of a single viral agent and to correlate between cytokine levels and
      leukocytes. Cerebrospinal fluid samples, collected during an outbreak of
      echovirus type 4 meningitis in infants and children in Israel, were tested for
      routine characteristics. In addition, cytokine levels were measured in 71
      meningitis patients and compared with those of 11 nonmeningitis patients.
      Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P < 0.01) and
      interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P < 0.01) were significantly
      higher in patients with meningitis than in the control group, whereas soluble
      intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did
      not differ significantly. In addition, only interleukin-6 levels correlated with
      leukocyte counts in viral meningitis patients. Interleukin-6 was the most
      sensitive and specific characteristic in predicting meningitis in this
      homogeneous group of patients. Furthermore, only interleukin-6 correlated with
      leukocyte counts in the cerebrospinal fluid.

PMID- 14643394
TI  - A simplified diagnostic approach to dizziness in children.
AB  - The objective of the study was to validate the effectiveness of a questionnaire
      and computer-assisted algorithm in diagnosing children with dizziness or vertigo.
      Dizziness and vertigo are common complaints in children, causing an extensive,
      often unnecessary evaluation. A pediatric "dizziness questionnaire" was designed
      and a computer-assisted algorithm was developed to facilitate the diagnostic
      task. A retrospective medical record review was conducted on all children
      presenting to the clinic for dizziness or vertigo throughout a 2-year period. The
      information was used by one investigator to complete the questionnaire and by the
      other, the algorithm. The two diagnoses thus obtained were compared by the third
      investigator to the medical record diagnosis. Sixty-two records were reviewed.
      The final diagnoses were migraine (39%), benign paroxysmal vertigo (15%),
      vestibular neuronitis (14%), and anxiety (13%). In 57 patients (92%), the
      questionnaire-derived diagnosis was identical to the medical record diagnosis. In
      52 patients (84%), the algorithm-derived diagnosis matched the medical record
      diagnosis. The questionnaire and computer-assisted algorithm are reliable
      diagnostic screening tools for children with dizziness or vertigo. When these
      tools combined provide a clear-cut diagnosis, no further evaluation is necessary.

PMID- 14643395
TI  - Reversible infantile hypoglycorrhachia: possible transient disturbance in glucose
      transport?
AB  - Facilitated glucose transporter isoform 1 deficiency syndrome (GLUT1 DS), caused
      by impaired GLUT1-mediated glucose transport into the brain, is characterized by
      hypoglycorrhachia. The defect in the facilitative glucose transporter isoform 1
      (GLUT1) can be confirmed by functional, quantitative, and molecular analyses.
      Diagnostic difficulties arise when these analyses are normal and
      hypoglycorrhachia remains unexplained. Three infants presenting with seizures and
      hypoglycorrhachia at 2, 4, and 6 weeks of age, which suggests GLUT1 deficiency
      syndrome, are reported. The seizures responded to a ketogenic diet in Patients 1
      and 3 and phenobarbitone in Patient 2. Repeated GLUT1 analyses were normal. When
      treatment was discontinued, all patients remained seizure-free and developed
      normally. Subsequent lumbar punctures showed the return to normoglycorrhachia. We
      conclude that these cases might represent a transient disturbance in GLUT1
      mediated glucose transport. The biomolecular basis for this clinical observation
      remains unknown. Though no treatment is required, clinical follow-up and repeated
      lumbar punctures are necessary to distinguish this benign condition from the
      original GLUT1 deficiency syndrome.

PMID- 14643396
TI  - Wavelet analysis for neonatal electroencephalographic seizures.
AB  - Electroencepholographs (EEGs) of neonatal seizures differ from those of children
      and adults. This study evaluated whether wavelet transform analysis, a
      nonstationary frequency analysis of EEG, can recognize and characterize neonatal
      seizures. Twenty-second segments were analyzed from 69 EEG seizures in 15
      neonatal patients whose seizures lasted 10 seconds or longer. The wavelet
      transform results were examined, as were EEG seizure durations and dominant
      frequencies. The wavelet transform results were correlated with the occurrence,
      after an 18-month follow-up, of postneonatal seizures. Wavelet transform analysis
      identified 40 seizures (58%) with a "sustained dominant frequency component" that
      lasted 10 seconds or longer and 29 seizures without a sustained dominant
      frequency component. The mean seizure duration of the 40 seizures with sustained
      dominant frequency components was 63.3 seconds, longer than the mean duration
      (33.6 seconds) of the seizures without sustained dominant frequency components, P
      < 0.01. Eleven patients manifested postneonatal epileptic seizures. Fifty-two EEG
      seizures in these 11 patients revealed more sustained dominant frequency
      components (74%) than 17 seizures in the 4 patients without postneonatal seizures
      (only 12%), P < 0.05. Wavelet transform analysis can identify neonatal EEG
      seizures and characterize their epileptic components. The presence of sustained
      dominant frequency components may predict postneonatal epileptic seizures.

PMID- 14643397
TI  - Transient global amnesia in a young adult with cyanotic heart disease.
AB  - The etiology of transient global amnesia is poorly understood, particularly in
      children and young adults. Transient global amnesia may follow a wide range of
      precipitating events. Proposed causes have included vascular event, seizure, and
      migraine. A young man with cyanotic congenital heart disease experienced an
      episode of transient global amnesia in the setting of polycythemia. Differential
      diagnosis of acute confusional episodes in children should include transient
      global amnesia, as well as confusional migraine, and should include evaluation
      for underlying coagulation abnormalities and polycythemia.

PMID- 14643398
TI  - Cervical myelopathy in an adolescent with Hallervorden-Spatz disease.
AB  - Hallervorden-Spatz disease is a rare neurodegenerative disorder characterized by
      progressive dystonia, rigidity, and dementia. In these patients, chronic repeated
      dystonic movements, especially of the head and neck, can lead to excessive stress
      on the cervical spine, resulting in early degenerative changes and myelopathy.
      This report focuses on a young patient with Hallervorden-Spatz disease who
      presented with C4 to C5 cervical disk extrusion and cord compression because of
      premature spondylotic changes of the cervical spine. Other authors have
      documented cervical spondylosis caused by movement disorders, but there had been
      no reported cases of cervical myelopathy as a complication of Hallervorden-Spatz
      disease. Because these patients already manifest a longstanding and progressive
      neurologic disorder, clinicians may encounter difficulties recognizing the
      symptoms and signs of new cervical pathology, especially if the spondylosis and
      myelopathy has an insidious onset. For follow-up of patients with Hallervorden
      Spatz disease who have multiple disabilities, a multidisciplinary approach with
      active involvement of physiotherapists, occupational and speech therapists,
      experienced nurses, caregivers, and clinicians is recommended. The clinician
      should also monitor the neurologic and functional status of the patient and
      screen for cervical pathology if suspicion arises. Good control of dystonia may
      be helpful in prevention of cervical spondylosis but may be difficult to achieve.
      Treatment modalities for dystonia are also discussed.

PMID- 14643399
TI  - Frontal foramina, Chiari II malformation, and hydrocephalus in a female.
AB  - Reported is a 4-year-old female with Chiari II malformation and congenital
      hydrocephalus associated with lumbosacral myelomeningocele who also presented
      with frontal calvarial foramina depicted by head computed tomographic scans with
      three-dimensional reconstructions. Magnetic resonance demonstrated bilateral and
      symmetric frontal lobe malformation-separated-lip clefts schizencephaly-adjacent
      to the bilateral frontal calvarial foramina. Because the different types of
      malformations evident in this patient do not share the same developmental origin,
      the association of findings is unusual and suggests the occurrence of an unknown
      prenatal factor acting along different stages of central nervous system
      development.

PMID- 14643400
TI  - Severe bilateral carpal tunnel syndrome in juvenile chronic arthritis.
AB  - Carpal tunnel syndrome, although rare, is known to occur in children mainly
      because of genetic or metabolic disorders. The clinical findings are variable and
      include symptoms of burning pain, tingling, numbness, and weakness or atrophy in
      the hands of the patients. It is usually diagnosed by demonstration of prolonged
      distal latency times during the electrodiagnostic studies. Reported here is a
      patient with juvenile chronic arthritis and a diagnosis of severe bilateral
      carpal tunnel syndrome, the first patient reported in the literature, to the best
      of the authors' knowledge.

PMID- 14643401
TI  - Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies.
AB  - Miller Fisher syndrome is characterized by a triad of ataxia, ophthalmoplegia,
      and reduced or absent tendon reflexes, with minimal if any limb weakness. Anti
      GQ1b immunoglobulin G antibodies are present in high titers in most patients.
      Presented is a two-year-old female with Miller Fisher syndrome whose blood serum
      was negative for anti-GQ1b immunoglobulin G antibodies.

PMID- 14643403
TI  - The csgD promoter, a control unit for biofilm formation in Salmonella
      typhimurium.
AB  - Expression of cellulose and curli fimbriae in Salmonella typhimurium is dependent
      on the transcriptional regulator CsgD. Transcription of csgD itself is influenced
      by a variety of regulatory stimuli. Complex nucleoprotein arrangements modulate
      the transcriptional activity of csgD and trigger the transition between the
      planktonic status and biofilm formation.

PMID- 14643404
TI  - Antagonistic interactions among Fusobacterium nucleatum and Prevotella intermedia
      with oral lactobacilli.
AB  - Microbiota residing in oral ecosystems show great complexity because of the
      mutual interdependence of certain microorganisms that might influence their
      presence or absence at a given site. The aim of this work was to evaluate
      possible antagonistic interactions among Fusobacterium nucleatum and Prevotella
      intermedia, isolated from periodontal pockets, and Lactobacillus casei, L.
      salivarius, L. rhamnosus and L. plantarum isolated from saliva. Different tests
      were carried out using each strain as an effector as well as a sensitive strain,
      alternatively: (1) agar diffusion with paper disks embedded with supernatants and
      pellets in different culture media; (b) the well diffusion assay; (c) the double
      layer method; and (d) OD(560) measurements of the kinetic growth of Lactobacillus
      strains in LAPTg broth with different volumes of F. nucleatum supernatant. P.
      intermedia supernatant did not have an inhibitory effect on Lactobacillus growth,
      except for L. casei, when the double plaque method was used. F. nucleatum
      supernatant inhibited growth of all Lactobacillus strains when the well diffusion
      method was used. F. nucleatum inhibited L. casei growth whatever the method used.
      The substance responsible for inhibition was a thermoresistant extracellular
      protein which was hydrolyzed by trypsin-like proteases. None of the species of
      lactobacilli studied inhibited the growth of P. intermedia or F. nucleatum.

PMID- 14643405
TI  - Study on experimental infections of Spiroplasma from the Chinese mitten crab in
      crayfish, mice and embryonated chickens.
AB  - Tremor disease (TD) of the Chinese mitten crab Eriocheir sinensi has become a
      serious disease in the Chinese freshwater culture industry in recent years. The
      agent, belonging to Spiroplasma, was purified from yolk and allantoic fluids of
      chicken embryos and was then inoculated into the body of crayfish, the abdominal
      cavity of ICR mice and the allantoid of chicken embryos, respectively. Thirty
      eight days after the inoculation, the mice and crayfish were dissected and their
      tissues sampled and observed with both the light and electron microscope. No
      infection was detected in mouse or crawfish tissue. But when the different
      tissues from the inoculated embryonated chickens were tested, the agent was
      detected only in the brain of embryonated chickens. This indicated that the agent
      represented a neurotropic characteristic in embryonated chickens, just as it had
      in the crab. This infective characteristic may be due to the development and
      maturation of host immunity.

PMID- 14643406
TI  - Cloning and characterization of a thermostable intracellular alpha-amylase gene
      from the hyperthermophilic bacterium Thermotoga maritima MSB8.
AB  - The gene encoding an intracellular alpha-amylase, AmyB (TM1650), from Thermotoga
      maritima MSB8, a hyperthermophilic bacterium, was cloned and expressed in
      Escherichia coli. The AmyB enzyme hydrolyzed alpha-1,4 starch linkage. The amyB
      gene is 1269 bp in length, encoding a protein of 422 amino acids (calculated
      molecular mass of 50187 Da). The molecular weight of the enzyme was estimated to
      be 50000 Da by SDS-PAGE after starch-nondenaturing-PAGE. The amino acid sequence
      of AmyB showed less than 12% identity to other amylases, but contained four
      regions that are highly conserved among alpha-amylases. The AmyB alpha-amylase
      exhibited maximal enzymatic activity at pH 7.0 and its optimum temperature for
      activity was 70 degrees C. Like the alpha-amylases of many other organisms, the
      thermostability of T. maritima MSB8 alpha-amylase, AmyB expressed in E. coli was
      enhanced in the presence of Ca(2+) (10 mM).

PMID- 14643407
TI  - Differentiation of Fonsecaea pedrosoi mycelial forms into sclerotic cells is
      induced by platelet-activating factor.
AB  - Platelet-activating factor (PAF) has been shown to induce the differentiation of
      several cell types. In this work, we evaluated the effects of PAF on the
      formation of sclerotic cells of Fonsecaea pedrosoi, the major causative agent of
      chromoblastomycosis. Cell differentiation was evaluated by light and electron
      microscopy, which showed that treatment of mycelial forms with PAF results in the
      generation of sclerotic bodies with typical morphological characteristics.
      Biochemical features of PAF-induced sclerotic cells were also analyzed and
      compared with those from sclerotic forms induced by propranolol, a previously
      described differentiating agent of F. pedrosoi. Chemical analyses of lipid and
      carbohydrate components from PAF- or propranolol-induced sclerotic bodies
      revealed that palmitic, stearic, oleic and linoleic acids were the major fatty
      acid components, while glucose, mannose, galactose and rhamnose were detected as
      the principal sugar constituents in these cells. Surface carbohydrate components
      of PAF- and propranolol-induced sclerotic cells were also evaluated, by flow
      cytometry analysis with twelve different lectins. The profile of reactivity of
      PAF- or propranolol-induced fungal cells with lectins was also very similar.
      Hydrolysis of the synthetic substrate p-nitrophenylphosphate by fungal cells
      demonstrated that the addition of PAF or propranolol to the mycelial cultures
      similarly promotes a significant increase in ecto-phosphatase activity. These
      results indicate that the differentiation of F. pedrosoi mycelial cells induced
      by PAF generates authentic sclerotic forms, as confirmed by the analysis of
      morphological and biochemical attributes. Since PAF is synthesized in normal
      conditions by the human host, these observations may have a correlation with the
      differentiation of F. pedrosoi in vivo.

PMID- 14643408
TI  - Proteomic analysis of the benzoate degradation pathway in Acinetobacter sp. KS-1.
AB  - The purpose of this study was to perform proteome analysis of Acinetobacter sp.
      KS-1, a bacterium capable of degrading benzoate as a sole carbon source. In order
      to understand the benzoate degradation pathway used by strain KS-1, proteomes of
      benzoate-cultured and succinate-cultured KS-1 were comparatively analyzed by two
      dimensional gel electrophoresis (2-DE). Eighteen protein spots proteins were
      exclusively induced from the benzoate-cultured strain KS-1. Of these 18 spots,
      two benzoate-degrading enzymes (catechol 1,2-dioxygenase and beta-ketoadipate
      succinyl-CoA transferase) were identified by MS/MS analysis by MALDI-TOF/TOF mass
      spectrometry, which suggests that strain KS-1 degrades benzoate by the beta
      ketoadipate pathway. DEAE-chromatography suggested that strain KS-1 induced only
      one type of catechol 1,2-dioxygenase during benzoate degradation. The catechol
      1,2-dioxygenase was purified using three steps of ammonium sulfate precipitation,
      DEAE-sepharose, and Mono-Q chromatography. The purified catechol 1,2-dioxygenase
      of strain KS-1 had strong dioxygenase activity for 4-methylcatechol as well as
      catechol. Sequencing analysis using N-terminal and internal amino acid sequences
      showed that this catechol 1,2-dioxygenase is highly homologous with catechol 1,2
      dioxygenase of Acinetobacter radioresistens. These results suggest that
      comparative proteomic analysis of biodegrading bacteria cultured under different
      conditions may be a useful initial step toward the elucidation of the aromatic
      compound degradation pathway.

PMID- 14643409
TI  - Isolation and characterization of two exopolysaccharides produced by
      Lactobacillus plantarum EP56.
AB  - A Lactobacillus plantarum strain producing exopolysaccharides (EPSs) was isolated
      from corn silage. When this strain, named L. plantarum EP56, was grown on a
      chemically defined medium, two EPS fractions were isolated. The cell-bound EPS
      fraction (EPS-b) was composed of a single high-molecular-mass polymer of
      8.5x10(5) Da containing glucose, galactose and N-acetylgalactosamine in a molar
      ratio of approximately 3:1:1 and traces of glycerol and phosphoglycerol. The
      released EPS fraction (EPS-r) was composed of the high-molecular-mass bound
      polysaccharide and a second polymer of 4x10(4) Da containing glucose, galactose
      and rhamnose in a molar ratio of 3:1:1 and traces of glycerol and
      phosphoglycerol. EPS-b and EPS-r contained phosphate which contributes to their
      negative net charge. Studies on polysaccharide production and location showed
      that both polymers were synthesized during the exponential growth phase and that
      the EPS-b polymer was progressively released into the culture medium during the
      stationary growth phase. Carbon source and temperature influenced EPS synthesis
      when L. plantarum EP56 was grown in a chemically defined medium. Lactose was the
      most efficient carbon source among the five tested (glucose, galactose, fructose,
      lactose and sucrose). EPS production was also increased when the incubation
      temperature is lowered.

PMID- 14643411
TI  - Complexities of chromium carcinogenesis: role of cellular response, repair and
      recovery mechanisms.
AB  - Certain hexavalent chromium (Cr(VI))-containing compounds are recognized
      occupational human lung carcinogens and may pose an environmental health risk.
      The carcinogenicity of Cr(VI) is targeted to particulate forms of moderate to low
      solubility. Soluble Cr(VI) oxyanions in the immediate cellular microenvironment
      traverse the cell membrane by non-specific anionic transporters. Cr(VI) is
      reductively metabolized within cells by agents including ascorbic acid (Asc),
      glutathione (GSH) and cysteine (Cys). During Cr(VI) reduction, a diverse range of
      genetic lesions are generated including Cr-DNA binary (mono) adducts, Cr-DNA
      ternary adducts, DNA protein crosslinks (DPCs), bi-functional (DNA interstrand
      crosslinks (ICLs)) adducts, single-strand breaks (SSBs) and oxidized bases. Some
      forms of Cr damage, such as ICLs, present physical barriers to DNA
      replication/transcription and, thus, likely promote a terminal cell fate such as
      apoptosis or terminal growth arrest. Other lesions, such as ternary DNA adducts,
      are potentially pre-mutagenic. Cr(VI) exposure elicits a classical DNA damage
      response within cells including activation of the p53 signaling pathway and cell
      cycle arrest or apoptosis. Moreover, Cr(VI) also induces the ATM-dependent DNA
      damage response pathway which is paradoxically required for both apoptosis and
      survival after Cr(VI) insult. In yeast, moderately cytotoxic concentrations of
      Cr(VI) result in an initial G1 arrest and delayed S phase progression, whereas
      less toxic levels of Cr(VI) induce G2 arrest, which requires homologous
      recombination for exit and survival. The past several years has witnessed many
      important advances in our understanding of the genetic/cellular damage produced
      by exposure to Cr(VI). Further information is needed regarding the potential
      involvement of oxygen radicals in Cr genotoxicity, the specific DNA repair
      pathways activated by Cr and the complex signaling mechanisms involved in the
      cellular response to Cr(VI). These pertinent issues must be considered in
      relation to the potential role that each plays in the induction of human
      respiratory tract cancer by particulate Cr(VI) compounds.

PMID- 14643412
TI  - Mechanism of arsenic carcinogenesis: an integrated approach.
AB  - Epidemiological evidence shows an association between inorganic arsenic in
      drinking water and increased risk of skin, lung and bladder cancers. The lack of
      animal models has hindered mechanistic studies of arsenic carcinogenesis in the
      past, but some promising new models for these cancers are now available. The
      various forms of arsenic to which humans are exposed, either directly or via
      metabolism of inorganic arsenic to various methylated forms, further complicate
      the issue of mechanism, since these compounds can have different effects, both
      genotoxic and non-genotoxic. This review will try to integrate all of these
      issues, with a strong bias toward effects that are produced by environmentally
      relevant arsenic concentrations.

PMID- 14643413
TI  - Nickel carcinogenesis.
AB  - Human exposure to highly nickel-polluted environments, such as those associated
      with nickel refining, electroplating, and welding, has the potential to produce a
      variety of pathologic effects. Among them are skin allergies, lung fibrosis, and
      cancer of the respiratory tract. The exact mechanisms of nickel-induced
      carcinogenesis are not known and have been the subject of numerous epidemiologic
      and experimental investigations. These mechanisms are likely to involve genetic
      and epigenetic routes. The present review provides evidence for the genotoxic and
      mutagenic activity of Ni(II) particularly at high doses. Such doses are best
      delivered into the cells by phagocytosis of sparingly soluble nickel-containing
      dust particles. Ni(II) genotoxicity may be aggravated through the generation of
      DNA-damaging reactive oxygen species (ROS) and the inhibition of DNA repair by
      this metal. Broad spectrum of epigenetic effects of nickel includes alteration in
      gene expression resulting from DNA hypermethylation and histone hypoacetylation,
      as well as activation or silencing of certain genes and transcription factors,
      especially those involved in cellular response to hypoxia. The investigations of
      the pathogenic effects of nickel greatly benefit from the understanding of the
      chemical basis of Ni(II) interactions with intracellular targets/ligands and
      oxidants. Many pathogenic effects of nickel are due to the interference with the
      metabolism of essential metals such as Fe(II), Mn(II), Ca(II), Zn(II), or Mg(II).
      Research in this field allows for identification of putative Ni(II) targets
      relevant to carcinogenesis and prediction of pathogenic effects caused by
      exposure to nickel. Ultimately, the investigations of nickel carcinogenesis
      should be aimed at the development of treatments that would inhibit or prevent
      Ni(II) interactions with critical target molecules and ions, Fe(II) in
      particular, and thus avert the respiratory tract cancer and other adverse health
      effects in nickel workers.

PMID- 14643414
TI  - Beryllium: genotoxicity and carcinogenicity.
AB  - Beryllium (Be) has physical-chemical properties, including low density and high
      tensile strength, which make it useful in the manufacture of products ranging
      from space shuttles to golf clubs. Despite its utility, a number of standard
      setting agencies have determined that beryllium is a carcinogen. Only a limited
      number of studies, however, have addressed the underlying mechanisms of the
      carcinogenicity and mutagenicity of beryllium. Importantly, mutation and
      chromosomal aberration assays have yielded somewhat contradictory results for
      beryllium compounds and whereas bacterial tests were largely negative, mammalian
      test systems showed evidence of beryllium-induced mutations, chromosomal
      aberrations, and cell transformation. Although inter-laboratory differences may
      play a role in the variability observed in genotoxicity assays, it is more likely
      that the different chemical forms of beryllium have a significant effect on
      mutagenicity and carcinogenicity. Because workers are predominantly exposed to
      airborne particles which are generated during the machining of beryllium metal,
      ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic
      activity of beryllium should be performed with relevant chemical forms of
      beryllium.

PMID- 14643415
TI  - Cadmium carcinogenesis.
AB  - Cadmium is a heavy metal of considerable environmental and occupational concern.
      Cadmium compounds are classified as human carcinogens by several regulatory
      agencies. The most convincing data that cadmium is carcinogenic in humans comes
      from studies indicating occupational cadmium exposure is associated with lung
      cancer. Cadmium exposure has also been linked to human prostate and renal cancer,
      although this linkage is weaker than for lung cancer. Other target sites of
      cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are
      considered equivocal. In animals, cadmium effectively induces cancers at multiple
      sites and by various routes. Cadmium inhalation in rats induces pulmonary
      adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce
      tumors and/or preneoplastic lesions within the rat prostate after ingestion or
      injection. At relatively high doses, cadmium induces benign testicular tumors in
      rats, but these appear to be due to early toxic lesions and loss of testicular
      function, rather than from a specific carcinogenic effect of cadmium. Like many
      other metals, cadmium salts will induce mesenchymal tumors at the site of
      subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance
      of these is dubious. Other targets of cadmium in rodents include the liver,
      adrenal, pancreas, pituitary, and hematopoietic system. With the exception of
      testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly
      defined. Cadmium can cause any number of molecular lesions that would be relevant
      to oncogenesis in various cellular model systems. Most studies indicate cadmium
      is poorly mutagenic and probably acts through indirect or epigenetic mechanisms,
      potentially including aberrant activation of oncogenes and suppression of
      apoptosis.

PMID- 14643416
TI  - Facilitative mechanisms of lead as a carcinogen.
AB  - The carcinogenicity of lead compounds has received renewed attention because of
      continuing environmental and occupational sources of exposure in many countries.
      The epidemiological evidence for an association between lead exposures and human
      cancer risk has been strengthened by recent studies, and new data on mechanisms
      of action provide biological plausibility for assessing lead as a human
      carcinogen. Both epidemiological and mechanistic data are consistent with a
      facilitative role for lead in carcinogenesis, that is, lead by itself may not be
      both necessary and sufficient for the induction of cancer, but at a cellular and
      molecular level lead may permit or enhance carcinogenic events involved in DNA
      damage, DNA repair, and regulation of tumor suppressor and promoter genes. Some
      of these events may also be relevant to understanding mechanisms of lead-induced
      reproductive toxicity.

PMID- 14643417
TI  - Cobalt and antimony: genotoxicity and carcinogenicity.
AB  - The purpose of this review is to summarise the data concerning genotoxicity and
      carcinogenicity of Co and Sb. Both metals have multiple industrial and/or
      therapeutical applications, depending on the considered species. Cobalt is used
      for the production of alloys and hard metal (cemented carbide), diamond
      polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt
      may result in adverse health effects in different organs or tissues. Antimony
      trioxide is primarily used as a flame retardant in rubber, plastics, pigments,
      adhesives, textiles, and paper. Antimony potassium tartrate has been used
      worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been
      used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and
      in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal
      dust, of which occupational exposure is linked to an increased lung cancer risk,
      is proven to be genotoxic in vitro and in vivo. Possibly, production of active
      oxygen species and/or DNA repair inhibition are mechanisms involved. Given the
      recently provided proof for in vitro and in vivo genotoxic potential of hard
      metal dust, the mechanistic evidence of elevated production of active oxygen
      species and the epidemiological data on increased cancer risk, it may be
      advisable to consider the possibility of a new evaluation by IARC. Both trivalent
      and pentavalent antimony compounds are generally negative in non-mammalian
      genotoxicity tests, while mammalian test systems usually give positive results
      for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo
      potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting
      results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC.
      Human carcinogenicity data is difficult to evaluate given the frequent co
      exposure to arsenic. Possible mechanisms of action, including potential to
      produce active oxygen species and to interfere with DNA repair systems, still
      need further investigation.

PMID- 14643418
TI  - Iron overload and its association with cancer risk in humans: evidence for iron
      as a carcinogenic metal.
AB  - Unlike arsenic, chromium, or nickel, the carcinogenicity of iron is still under
      debate. In this review, evidence for iron as a carcinogenic metal was summarized
      from epidemiological, animal, and cell culture studies. The role of iron in
      various cancers, such as colorectal cancer and liver cancer was presented. Recent
      advancements on the molecular mechanisms of iron carcinogenesis were also
      reviewed. These include: (1) iron autoxidation involving only Fe(2+)+O2 in
      oxidant formation in biological systems and its pH dependency; (2) activation of
      oxidative responsive transcription factors and pro-inflammatory cytokines; and
      (3) iron-induced hypoxia signaling.

PMID- 14643419
TI  - Nitric oxide production by arsenite.
AB  - Arsenic can either enhance or reduce nitric oxide (NO) production, depending on
      the type of cell, the species and dose of arsenical tested. The mechanisms of how
      arsenic increases or decreases NO production remain unclear. Because NO is
      associated with many pathological conditions, it is conceivable that in those
      arsenic-target tissues, the NO production may be upregulated by continuous
      arsenic exposure, and a prolonged over-production of NO may cause inflammation
      hence a pathological condition. A prolonged interference with the normal
      physiological level of NO may also play a role in the initiation, promotion, and
      progression of arsenic-related human cancers. Suppression of NO production has
      been shown to reduce arsenite-induced oxidative DNA damage, inhibition of
      pyrimidine dimer excision, and micronuclei. However, a completely reliable story
      on how NO is involved in arsenic-related human disease is still lacking.

PMID- 14643420
TI  - Signaling by carcinogenic metals and metal-induced reactive oxygen species.
AB  - Epidemiological data indicate that exposure to metal and metalloid species,
      including arsenic(III), chromium(VI), and nickel(II), increases the risk of
      cancer, particularly of the lung and skin. Alterations in normal signal
      transduction as a result of exposure to carcinogenic metals, and to metal
      catalyzed reactive oxygen species (ROS) formation, appear to play an important
      role in the etiology of metal-induced carcinogenesis. Signaling components
      affected by metals include growth factor receptors, G-proteins, MAP kinases, and
      nuclear transcription factors. This article reviews current literature on the
      effects of carcinogenic metals and metal-induced ROS on cancer-related signaling
      pathways. In addition, the mechanisms by which those changes occur, and the role
      of those changes in carcinogenesis are discussed.

PMID- 14643421
TI  - Metallothioneins in human tumors and potential roles in carcinogenesis.
AB  - Metallothioneins (MT) are a group of low-molecular weight, cysteine rich
      intracellular proteins, which are encoded by a family of genes containing at
      least 10 functional isoforms in human. The expression and induction of these
      proteins have been associated with protection against DNA damage, oxidative
      stress and apoptosis. Moreover, MT may potentially activate certain
      transcriptional factors by donating zinc. Although MT is a cytosolic protein in
      resting cells, it can be translocated transiently to the cell nucleus during cell
      proliferation and differentiation. A number of studies have shown an increased
      expression of MT in various human tumors of the breast, colon, kidney, liver,
      lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary
      bladder. However, MT is down-regulated in certain tumors such as hepatocellular
      carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal
      to all human tumors, but may depend on the differentiation status and
      proliferative index of tumors, along with other tissue factors and gene
      mutations. In certain tumors such as germ cell carcinoma, the expression of MT is
      closely related to the tumor grade and proliferative activity. Increased
      expression of MT has also been observed in less differentiated tumors. Thus,
      expression of MT may be a potential prognostic marker for certain tumors. There
      are few reports on the expression of the different isoforms of MT which have been
      analyzed by specific gene probes. They reveal that certain isoforms are expressed
      in specific cell types. The factors which can influence MT induction in human
      tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors
      may be related to hypermethylation of the MT-promoter or mutation of other genes
      such as the p53 tumor suppressor gene. In vitro studies using human cancer cells
      suggest a possible role for p53 and the estrogen-receptor on the expression and
      induction of MT in epithelial neoplastic cells. Some of the evidence supporting a
      role for MT in both intrinsic and acquired drug resistance is critically
      evaluated in this review. Since chemoresistance in human tumors is a
      multifactorial phenomenon, it is difficult to conclude that MT is a more crucial
      factor than others. Therefore, additional experimental data on MT and its
      isoforms in human tumors, are needed to elucidate the biological functions of MT
      during tumor progression, along with other tumor markers.

PMID- 14643422
TI  - Signaling events for metallothionein induction.
AB  - Metallothioneins (MTs) are low molecular weight, cysteine-rich metal-binding
      proteins found in a wide variety of organisms including bacteria, fungi and all
      eukaryotic plant and animal species. They are the single most abundant group of
      intracellular zinc-binding proteins in eukaryotic cells [Prog. Food Nutr. Sci. 14
      (1990) 193]: 5-10% of zinc in human hepatocytes is bound to MTs [Methods Enzymol.
      205 (1991) 613; FEBS Lett. 39 (1974) 229]. A critical physiological role for MTs
      has been suggested to encompass control of zinc availability to proteins
      requiring zinc for activity, but has not been definitively described.
      Nevertheless, a hallmark of MT gene regulation is their pattern of expression in
      different cell types and tissues, and their inducibility by a host of chemical
      and physical agents acting directly or indirectly on multiple cis-acting motifs
      in the regulatory regions of MT genes [Prog. Nucleic Acid. Res. Mol. Biol., 66
      (2001) 357]. The pattern of physical and chemical events regulating basal MT gene
      transcription, and induction or repression of MT gene activity, provides valuable
      insight into the potential functions of MTs. In this review, we describe the
      transcriptional regulatory processes involved in MT gene expression.

PMID- 14643423
TI  - Metal-induced apoptosis: mechanisms.
AB  - The past decade has seen an intense focus on mechanisms of apoptosis. Many
      important observations on the various signaling pathways mediating apoptotic cell
      death have been made and our understanding of the importance of apoptosis in both
      normal growth and development and pathophysiology has greatly increased. In
      addition, mechanisms of metal-induced toxicity continue to be of interest given
      the ubiquitous nature of these contaminants. The purpose of this review is to
      summarize our current understanding of the apoptotic pathways that are initiated
      by metals, mainly established (arsenic, cadmium, chromium, nickel, beryllium) and
      possible (lead, antimony, cobalt) human carcinogens. Increased understanding of
      metal-induced apoptosis is critical to illuminate mechanisms of metal-induced
      carcinogenesis, as well as the potential of metal species (arsenic) as
      chemotherapeutic agents.

PMID- 14643424
TI  - DNA replication, the cell cycle and genome stability.

PMID- 14643425
TI  - Precocious G1/S transitions and genomic instability: the origin connection.
AB  - Both in yeast and in higher eukaryotes, genomic instability often ensues when the
      G1/S transition machinery is deregulated and cells are forced to enter S phase
      prematurely. This case of acquired mutability is particularly important, since a
      majority of genes mutated in human cancers encode factors that influence the G1/S
      transition. The precocious G1/S transition often results in a sub-optimal S
      phase. Moreover, the problems generated in such an S phase can escape detection
      by the cellular surveillance systems, allowing undeterred mitosis. This review
      focuses primarily on budding yeast data, where progress has been made in the past
      couple of years towards a mechanistic understanding of the underlying processes.
      A dual surveillance system is discussed, which relies on the presence of licensed
      but unfired origins and stalled replication forks to deter mitosis until
      replication is complete. Normally, this dual surveillance system allows S phase
      to be flexible in duration in a variety of growth conditions, when the fork
      density and/or fork progression rates can vary widely. However, precocious exit
      from G1 can have a disabling effect on this surveillance system. Premature exit
      from G1 can cut short the licensing of origins and the accumulation of resources
      for the upcoming replication, while giving a cell a false indication that it is
      metabolically ready to conduct S phase.

PMID- 14643426
TI  - Cdc7 kinases (DDKs) and checkpoint responses: lessons from two yeasts.
AB  - Principally characterized for its requirement in the initiation of DNA
      replication, compelling evidence from two yeast model organisms now points to a
      central role for the Dbf4/Cdc7 kinase complex in S-phase checkpoint responses.
      Among the key findings supporting this view are observations that orthologs Dfp1
      (Schizosaccharomyces pombe) and Dbf4 (Saccharomyces cerevisiae) interact with
      equivalent checkpoint kinases Cds1 and Rad53, respectively, and that mutants for
      Dbf4 and Cdc7 in these species are sensitive to genotoxic agents. Recently, these
      findings have been extended through mutational analyses of conserved regions in
      both Dfp1 and Dbf4, leading to the identification of distinct motifs which
      mediate cellular responses to DNA damage and replication fork arrest. The present
      review is a comparative survey of data obtained from studies conducted with S.
      pombe and S. cerevisae, and a consideration of models for the role played by
      Dbf4/Cdc7 in checkpoint responses.

PMID- 14643427
TI  - Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication
      and development.
AB  - Cdc7 kinase plays an essential role in firing of replication origins by
      phosphorylating components of the replication complexes. Cdc7 kinase has also
      been implicated in S phase checkpoint signaling downstream of the ATR and Chk1
      kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C
      DNA content after completion of the ongoing DNA replication. In contrast,
      conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES)
      cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting
      requirement of Cdc7 functions for continuation of ongoing DNA synthesis.
      Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51
      foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53
      becomes highly activated and the cells undergo massive p53-dependent apoptosis.
      Thus, defective origin activation in mammalian cells can generate DNA replication
      checkpoint signals. Efficient removal of those cells in which replication has
      been perturbed, through cell death, may be beneficial to maintain the highest
      level of genetic integrity in totipotent stem cells. Partial, rather than total,
      loss of Cdc7 kinase expression results in retarded growth at both cellular and
      whole body levels, with especially profound impairment of germ cell development.

PMID- 14643428
TI  - The S-phase checkpoint and its regulation in Saccharomyces cerevisiae.
AB  - Cells are never more vulnerable than during DNA replication, which represents a
      major moment of potential genetic instability. Genotoxic insults induce many
      different forms of DNA damage that may interfere with the ability of cells to
      properly duplicate their genome. Primary damage may in turn undergo structural
      transformations during DNA replication, thus generating secondary lesions that
      may be even more dangerous. Cells experiencing replication of damaged DNA or
      replication blocks activate an S-phase checkpoint response that assures the
      fidelity and completion of DNA replication before cells enter M-phase. The S
      phase checkpoint pathway regulates not only progress through the cell cycle but
      also DNA repair and DNA replication itself.

PMID- 14643429
TI  - Checkpoint responses to replication stalling: inducing tolerance and preventing
      mutagenesis.
AB  - Replication mutants often exhibit a mutator phenotype characterized by point
      mutations, single base frameshifts, and the deletion or duplication of sequences
      flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can
      significantly affect the mutator phenotype. Here, we use fission yeast
      (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses
      to replication perturbations induced by replication mutants. Checkpoint
      activation induced by a DNA polymerase mutant, aside from delay of mitotic entry,
      up-regulates the translesion polymerase DinB (Polkappa). Checkpoint Rad9-Rad1
      Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5
      checkpoint complex in response to replication perturbation, recruits DinB onto
      chromatin to generate the point mutations and single nucleotide frameshifts in
      the replication mutator. This chain of events reveals a novel checkpoint-induced
      tolerance mechanism that allows cells to cope with replication perturbation,
      presumably to make possible restarting stalled replication forks. Fission yeast
      Cds1 kinase plays an essential role in maintaining DNA replication fork stability
      in the face of DNA damage and replication fork stalling. Cds1 kinase is known to
      regulate three proteins that are implicated in maintaining replication fork
      stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex;
      Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination
      during replication; and Rad60, a protein required for recombinational repair
      during replication. These Cds1-regulated proteins are thought to cooperatively
      prevent mutagenesis and maintain replication fork stability in cells under
      replication stress. These checkpoint-regulated processes allow cells to survive
      replication perturbation by preventing stalled replication forks from
      degenerating into deleterious DNA structures resulting in genomic instability and
      cancer development.

PMID- 14643430
TI  - Running into problems: how cells cope with replicating damaged DNA.
AB  - The ability of cells to fully and faithfully replicate DNA is essential for
      preventing genomic instability and cancer. DNA is susceptible to damage both in
      resting and in actively replicating cells. Thus, genome duplication necessarily
      involves replication of damaged DNA. The many mechanism cells use to avoid or
      overcome the problems of replicating an imperfect DNA template are discussed.

PMID- 14643432
TI  - Pathways for mitotic homologous recombination in mammalian cells.
AB  - Homologous recombination (HR) is essential for cellular survival in mammals. In
      this review, the substrates for HR, the pathways of repair, and their end
      products (i.e. sister chromatid exchange (SCE), gene conversion, deletions or
      tandem duplications) are discussed. HR is involved in the repair of DNA double
      strand breaks (DSBs) and DNA lesions that occur at replication forks. A classical
      DSB may result in deletions, tandem duplications or gene conversion following two
      end recombination repair. In contrast, a SCE may be the result of one-end
      recombination repair at a collapsed replication fork, i.e. a single-strand break
      converted into a DSB at a replication fork. Recombination repair at a stalled
      replication fork may occur in the absence of a DSB intermediate and may result in
      either SCE or gene conversion. Finally, substrates and pathways involved in
      spontaneous HR are discussed.

PMID- 14643433
TI  - Role of the error-free damage bypass postreplication repair pathway in the
      maintenance of genomic stability.
AB  - The postreplication repair pathway (PRR) is composed of error-free and error
      prone sub-pathways that allow bypass of DNA damage-induced replication-blocking
      lesions. The error-free sub-pathway is also used for bypass of spontaneous DNA
      damage and functions in cooperation with recombination pathways. In diploid yeast
      cells, error-free PRR is needed to prevent genomic instability, which is manifest
      as loss of heterozygosity (LOH) events of increased chromosome loss and
      recombination. Homologous recombination acts synergistically with the error-free
      damage avoidance branch of PRR to prevent chromosome loss. The DNA damage
      checkpoint gene MEC1 acts synergistically with the PRR pathway in maintaining
      genomic stability. Integration of the PRR pathway with other cellular pathways
      for preventing genomic instability is discussed. In diploid strains, the most
      dramatic increase is in the abnormality of chromosome loss when a repair or
      damage detection pathway is defective.

PMID- 14643434
TI  - Regulation of alternative replication bypass pathways at stalled replication
      forks and its effects on genome stability: a yeast model.
AB  - Replication-blocking lesions result in increased genomic instability by stalling
      replication forks. Eukaryotic cells appear to have evolved several surveillance
      and repair/bypass mechanisms to ensure that replication can be resumed at these
      stalled forks. In the yeast Saccharomyces cerevisiae, the helicases Srs2 and Sgs1
      appear to play a role in controlling the processing and stabilization of stalled
      replication forks. These proteins appear to be tightly regulated throughout the
      cell cycle and play a direct role in DNA-damage checkpoints. This allows the
      cells to determine the best mechanism to reestablish replication at the stalled
      fork: by shuttling the lesion into the RAD6-dependent pathway that can lead to
      error-free or error-prone bypass; or by using homologous recombination. Under
      conditions where both the RAD6-dependent pathway and recombination are disabled,
      the cells can bypass the lesion using a novel damage avoidance mechanism that is
      controlled by Mgs1. Replication fork bypass processes appear to be highly
      conserved within eukaryotes, with homologs for SGS1 and MGS1 found in both
      Schizosaccharomyces pombe and mammalian cells.

PMID- 14643431
TI  - Caffeine and human DNA metabolism: the magic and the mystery.
AB  - The ability of caffeine to reverse cell cycle checkpoint function and enhance
      genotoxicity after DNA damage was examined in telomerase-expressing human
      fibroblasts. Caffeine reversed the ATM-dependent S and G2 checkpoint responses to
      DNA damage induced by ionizing radiation (IR), as well as the ATR- and Chk1
      dependent S checkpoint response to ultraviolet radiation (UVC). Remarkably, under
      conditions in which IR-induced G2 delay was reversed by caffeine, IR-induced G1
      arrest was not. Incubation in caffeine did not increase the percentage of cells
      entering the S phase 6-8h after irradiation; ATM-dependent phosphorylation of p53
      and transactivation of p21(Cip1/Waf1) post-IR were resistant to caffeine.
      Caffeine alone induced a concentration- and time-dependent inhibition of DNA
      synthesis. It inhibited the entry of human fibroblasts into S phase by 70-80%
      regardless of the presence or absence of wildtype ATM or p53. Caffeine also
      enhanced the inhibition of cell proliferation induced by UVC in XP variant
      fibroblasts. This effect was reversed by expression of DNA polymerase eta,
      indicating that translesion synthesis of UVC-induced pyrimidine dimers by DNA pol
      eta protects human fibroblasts against UVC genotoxic effects even when other DNA
      repair functions are compromised by caffeine.

PMID- 14643435
TI  - Evidence that yeast SGS1, DNA2, SRS2, and FOB1 interact to maintain rDNA
      stability.
AB  - We and others have proposed that faulty processing of arrested replication forks
      leads to increases in recombination and chromosome instability in Saccharomyces
      cerevisiae. Now we use the ribosomal DNA locus, which is a good model for all
      stages of DNA replication, to test this hypothesis. We showed previously that DNA
      replication pausing at the ribosomal DNA replication fork barrier (RFB) is
      accompanied by the occurrence of double-strand breaks near the RFB. Both pausing
      and breakage are elevated in the hypomorphic dna2-2 helicase mutant. Deletion of
      FOB1 suppresses the elevated pausing and DSB formation. Our current work shows
      that mutation inactivating Sgs1, the yeast RecQ helicase ortholog, also causes
      accumulation of stalled replication forks and DSBs at the rDNA RFB. Either
      deletion of FOB1, which suppresses fork blocking and certain types of rDNA
      recombination, or an increase in SIR2 gene dosage, which suppresses rDNA
      recombination, reduces the number of forks persisting at the RFB. Although dna2-2
      sgs1Delta double mutants are conditionally lethal, they do not show enhanced rDNA
      defects compared to sgs1Delta alone. However, surprisingly, the dna2-2 sgs1Delta
      lethality is suppressed by deletion of FOB1. On the other hand, the dna2-2
      sgs1Delta lethality is only partially suppressed by deletion of rad51Delta. We
      propose that the replication-associated defects that we document in the rDNA are
      characteristic of similar events occurring either stochastically throughout the
      genome or at other regions where replication forks move slowly or stall, such as
      telomeres, centromeres, or replication slow zones.

PMID- 14643436
TI  - Repair of and checkpoint response to topoisomerase I-mediated DNA damage.
AB  - Topoisomerase I (Top1) catalyzes two transesterification reactions: single-strand
      DNA cleavage and religation that are normally coupled for the relaxation of DNA
      supercoiling in transcribing and replicating chromatin. A variety of endogenous
      DNA modifications, potent anticancer drugs and carcinogens uncouple these two
      reactions, resulting in the accumulation of Top1 cleavage complexes. Top1
      cleavage complexes damage DNA and kill cells by generating replication-mediated
      DNA double-strand breaks (DSBs) and by stalling transcription complexes. The
      repair of Top1-mediated DNA lesions involves integrated pathways that are
      conserved from yeasts to humans. Top1-mediated DNA damage and cell cycle
      checkpoint responses can be studied biochemically and genetically in yeast and
      human cells with known genetic defects. Defects in these repair/checkpoint
      pathways, which promote tumor development, explain, at least in part, the
      selectivity of camptothecins and other Top1 inhibitors for cancer cells.

PMID- 14643437
TI  - Comparison of hypoxia-induced replication arrest with hydroxyurea and aphidicolin
      induced arrest.
AB  - Severe levels of hypoxia (oxygen concentrations of less that 0.02%) have been
      shown to induce a rapid S-phase arrest. The mechanism behind hypoxia-induced S
      phase arrest is unclear, we show here that it was not mediated by a shortage of
      nucleosides and was not dependent on p53, p21 or Hif 1alpha status. The drugs
      aphidicolin and hydroxyurea both induce rapid replication arrest and have been
      used throughout the literature to study the ATR-mediated response to stalled
      replication. We have shown previously that hypoxia induces ATR-dependent
      phosphorylation of p53, Chk1 and histone H2AX. Using comet-assays to detect DNA
      damage we found that both aphidicolin and hydroxyurea induced significant levels
      of DNA-damage while hypoxia did not. Here we show that like aphidicolin and
      hydroxyurea, hypoxia induces phosphorylation of Nbs1 at serine 343 and Rad17
      serine 645. Hypoxia-dependent phosphorylation of Nbs1 and Rad17 was ATM
      independent and therefore likely to be a result of the ATR kinase activity. In
      contrast, p53 was phosphorylated differentially in response to the three
      treatments considered here. p53 was phosphorylated at serine 15 in response to
      all three treatments but was only phosphorylated at serine 20 in response to the
      drug treatments. We propose that treatment with either aphidicolin or hydroxyurea
      leads to not only replication arrest but also DNA-damage and therefore both ATM
      and ATR-mediated signaling. In contrast replication arrest induced by severe
      hypoxia is sensed exclusively through ATR, with ATM only having a role to play
      after re-oxygenation.

PMID- 14643438
TI  - Comparison of checkpoint responses triggered by DNA polymerase inhibition versus
      DNA damaging agents.
AB  - To better understand the different cellular responses to replication fork pausing
      versus blockage, early DNA damage response markers were compared after treatment
      of cultured mammalian cells with agents that either inhibit DNA polymerase
      activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA
      damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and
      adozelesin). These agents were compared for their relative abilities to induce
      phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear
      focalization of gamma-H2AX and RPA. Treatment by aphidicolin and HU resulted in
      phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of
      gamma-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop
      replication fork progression, did not abrogate HU-induced gamma-H2AX and RPA
      focalization. This suggests that HU may act on the replication fork machinery
      directly, such that fork progression is not required to trigger these responses.
      The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced
      phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the
      pattern of MMS-induced RPA focalization did not match the BUdR incorporation
      pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is
      not replication fork-dependent. In support of this, MMS was the only reagent used
      that did not induce phosphorylation of Chk1. These results indicate that
      induction of DNA damage checkpoint responses due to adozelesin is both
      replication fork and fork progression dependent, induction by HU is replication
      fork dependent but progression independent, while induction by MMS is independent
      of both replication forks and fork progression.

PMID- 14643439
TI  - Apoptosis-like yeast cell death in response to DNA damage and replication
      defects.
AB  - In budding (Saccharomyces cerevisiae) and fission (Schizosaccharomyces pombe)
      yeast and other unicellular organisms, DNA damage and other stimuli can induce
      cell death resembling apoptosis in metazoans, including the activation of a
      recently discovered caspase-like molecule in budding yeast. Induction of
      apoptotic-like cell death in yeasts requires homologues of cell cycle checkpoint
      proteins that are often required for apoptosis in metazoan cells. Here, we
      summarize these findings and our unpublished results which show that an important
      component of metazoan apoptosis recently detected in budding yeast-reactive
      oxygen species (ROS)-can also be detected in fission yeast undergoing an
      apoptotic-like cell death. ROS were detected in fission and budding yeast cells
      bearing conditional mutations in genes encoding DNA replication initiation
      proteins and in fission yeast cells with mutations that deregulate cyclin
      dependent kinases (CDKs). These mutations may cause DNA damage by permitting
      entry of cells into S phase with a reduced number of replication forks and/or
      passage through mitosis with incompletely replicated chromosomes. This may be
      relevant to the frequent requirement for elevated CDK activity in mammalian
      apoptosis, and to the recent discovery that the initiation protein Cdc6 is
      destroyed during apoptosis in mammals and in budding yeast cells exposed to
      lethal levels of DNA damage. Our data indicate that connections between apoptosis
      like cell death and DNA replication or CDK activity are complex. Some apoptosis
      like pathways require checkpoint proteins, others are inhibited by them, and
      others are independent of them. This complexity resembles that of apoptotic
      pathways in mammalian cells, which are frequently deregulated in cancer. The
      greater genetic tractability of yeasts should help to delineate these complex
      pathways and their relationships to cancer and to the effects of apoptosis
      inducing drugs that inhibit DNA replication.

PMID- 14643440
TI  - G2 and spindle assembly checkpoint adaptation, and tetraploidy arrest:
      implications for intrinsic and chemically induced genomic instability.
AB  - While checkpoints that act in S-phase are essential to the maintenance of genomic
      stability, these checkpoints do not act alone. Additionally, G2 DNA damage
      checkpoints, the spindle assembly checkpoint, and a post-mitotic G1 tetraploidy
      checkpoint act subsequent to DNA replication to ensure genetic fidelity in cell
      division. In this review, we will examine how these checkpoints cooperate in the
      maintenance of genomic stability in response to either DNA damage or cytoskeletal
      disruption. Since the G2 and spindle assembly checkpoints are subject to
      adaptation, we will discuss how the G1 tetraploidy checkpoint acts in concert
      with these checkpoints to mediate stable arrest. We will also probe the
      relationship of these checkpoints by exploring common features of their
      regulation. Finally, the consequences of malfunction of these checkpoints for
      both intrinsic and chemically induced genomic instability will be examined. Among
      these consequences are aneuploidization, extranumerary centrosomes, and
      micronucleation.

PMID- 14643441
TI  - Marginal dietary thiamin deficiency induces the formation of colonic aberrant
      crypt foci (ACF) in rats.
AB  - Thiamin deficiency leads to the endogenous formation of genotoxic alpha
      oxoaldehydes (glyoxals). To evaluate whether marginal deficiency poses a
      carcinogenesis risk we fed rats AIN-76A sucrose-based diets containing thiamin at
      4.9 (control), 1.6 or 1.0 mg/kg diet and examined their colons after 160 days.
      Reduced thiamin increased aberrant crypt foci (ACF) from 1.14+/-0.46 to 3.70+/
      1.17 and 2.60+/-1.02 ACF/colon in the absence of exogenous carcinogen or of
      symptoms of beriberi. Since typical Western diets can provide marginal levels of
      thiamin with high levels of simple sugars, individuals could be exposed to an
      increased risk of colon and perhaps other cancers.

PMID- 14643442
TI  - Chemoprevention of mammary carcinogenesis in female rats by rofecoxib.
AB  - Epidemiological and experimental studies indicate that non-steroidal anti
      inflammatory drugs play role in the prevention of human neoplasia including
      mammary gland cancer. In this study, tumour suppressive effects of a selective
      inhibitor of cyclooxygenase-2 (COX-2) rofecoxib in the prevention of N-methyl-N
      nitrosourea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats
      were evaluated. Rofecoxib was dietary administered in two concentrations-0.01
      mg/1 g (ROFE 0.001%), or 0.05 mg/1 g (ROFE 0.005%). Rofecoxib decreased the
      incidence by 40% (ROFE 0.001%) and by 42.5% (ROFE 0.005%) (P=0.043) when compared
      to the control group. Similarly, tumour frequency and tumour volume decreased
      depending on an increasing rofecoxib dose by 18.5 or 40% (tumour frequency) and
      by 35 or 43% (tumour volume). Rofecoxib shifted the rate of fibroadenomas from
      15% (control group) to 32% (ROFE 0.001%), or 38% (ROFE 0.005%), respectively. The
      present study points to pronounced dose-dependent tumour suppressive effects of
      rofecoxib in mammary carcinogenesis.

PMID- 14643443
TI  - Prepubertal resveratrol exposure accelerates N-methyl-N-nitrosourea-induced
      mammary carcinoma in female Sprague-Dawley rats.
AB  - The major object of this study was to characterize the effect of prepubertal
      trans-3,4',5-trihydroxystilbene (resveratrol) exposure on N-methyl-N-nitrosourea
      (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Prepubertal
      rats (15 to 19 days of age) were treated daily with either 10 or 100 mg/kg
      resveratrol for 5 days, and were compared with resveratrol-untreated animals (30
      rats in each group). Six rats in each group were autopsied at 49 days of age, and
      their growth was evaluated. All remaining rats were given 50 mg/kg MNU, followed
      by monitoring for occurrence of mammary carcinoma. A dose of 100 mg/kg (but not
      10 mg/kg) resveratrol significantly increased incidence of rat with mammary
      carcinomas > or =1 cm and multiplicity (all histologically detected mammary
      carcinomas per rat), but did not affect latency, compared with untreated
      controls. Resveratrol did not affect body weight increase, but 100 mg/kg
      resveratrol caused slightly earlier vaginal opening. Although all rats cycled,
      resveratrol-treated animals exhibited significantly increased irregularity of
      estrous cycle, spending more time in the estrus phase. Thus, short resveratrol
      treatment of prepubertal female rats affected endocrine function, and accelerated
      development of MNU-induced mammary carcinomas.

PMID- 14643444
TI  - Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study
      of oral cancer chemoprevention.
AB  - The anticarcinogenic effect of phenethyl isothiocyanate (PEITC) was examined in
      hamster buccal pouch mucosa exposed to N-nitrosomethylbenzylamine (NMBA).
      Unscheduled DNA synthesis (UDS) and induction of intraepithelial gamma-glutamyl
      transpeptidase (gamma-GT) histochemical foci were assessed as potential
      predictors of anticarcinogenicity. UDS mediated by in vitro exposure to NMBA (at
      10 and 50 mM) was examined in mucosal samples derived following topical exposure
      of pouch mucosa to PEITC at concentrations of 0.5, 5, or 50 mM. In vivo PEITC
      pretreatment reduced NMBA-induced UDS in a dose dependent manner. PEITC treatment
      reduced induction of gamma-GT foci, detected in epithelial wholemounts derived
      over a period of 8-13 weeks of NMBA application, by an average of 96%. PEITC also
      reduced tumor formation by 94%. gamma-GT, in particular, may be a useful
      indicator for identification of effective oral cancer chemopreventive agents and
      combinations of agents.

PMID- 14643445
TI  - Protective antitumor immunity induced by fixed tumor cells in combination with
      adjuvant in a murine hepatoma model.
AB  - We previously reported that fixed tumor sections induced autologous cytotoxic T
      lymphocytes (CTL) from human peripheral blood lymphocytes in vitro. Here, we
      examined whether fixed tumor cells could stimulate in vivo immunity using a
      murine hepatoma model. Vaccination of syngeneic mice with fixed Hepa 1-6 cells in
      combination with OK-432 and tuberculin as an adjuvant resulted in a significant
      increase in survival of mice against live Hepa 1-6 cell challenge. In addition,
      the splenocytes from vaccinated mice secreted CD4(+) T cell-mediated interferon
      gamma (IFN-gamma) and exhibited a specific CTL response. These findings suggest
      that fixed tumor cells combined with an appropriate adjuvant induce effective
      antitumor immunity in vivo.

PMID- 14643446
TI  - N-Caffeoyltyramine arrests growth of U937 and Jurkat cells by inhibiting protein
      tyrosine phosphorylation and inducing caspase-3.
AB  - N-Cinnamoyltyramine, N-caffeoyltyramine, N-feruloyltyramine, and N
      sinapoyltyramine were synthesized and investigated to identify the most potent
      compound with anti-proliferation effect on HL-60, U937 and Jurkat cells. N
      Caffeoyltyramine was the most potent with GI(50)=10 microM. The treatment of the
      cells with N-caffeoyltyramine activated caspase-3 activity, and inhibited the
      growth of cells via decreasing in protein tyrosine kinase activity including
      epidermal growth factor receptor. These data indicate that N-caffeoyltyramine is
      most potent compound, inducing cell death of the cancer cells by inhibiting
      protein tyrosine kinases and activating caspase-3 activity.

PMID- 14643447
TI  - Alteration of urinary profiles of endogenous steroids and polyunsaturated fatty
      acids in thyroid cancer.
AB  - To explore the possible involvement of a relationship between steroids and
      polyunsaturated fatty acids (PUFAs) in thyroid cancer, we studied the
      concentration levels of 21 endogenous urinary androgens and glucocorticoids, and
      6 urinary PUFAs in female patients with thyroid cancer (n=29, 49.4+/-12.6 years)
      and in normal female subjects (n=20, 48.3+/-11.9 years). Using gas chromatography
      mass spectrometry in selected ion-monitoring mode, we performed quantification of
      androgens, glucocorticoids, and PUFAs. In the case of the urinary androgens and
      the glucocorticoids, the concentration of androgens was not altered between
      patients with thyroid cancer and normal controls. However, the concentration of
      glucocorticoid significantly decreased in patients with thyroid cancer compared
      to that of the normal controls. Also, in case of urinary PUFAs, the precursor of
      cholesterol, the concentration of linoleic acid, arachidonic acid, and
      docosahexaenoic acid (DHA) were decreased in patient with thyroid cancer
      (P<0.05). In this results, it can be concluded that the glucocorticoids milieu
      induced from the decreasing urinary concentration of DHA may exert an important
      influence upon thyroid cancer. Consequently, the change of urinary
      glucocorticoids concentration may play an important role in thyroid cancer.

PMID- 14643448
TI  - Farnesyl-O-acetylhydroquinone and geranyl-O-acetylhydroquinone suppress the
      proliferation of murine B16 melanoma cells, human prostate and colon
      adenocarcinoma cells, human lung carcinoma cells, and human leukemia cells.
AB  - Farnesyl-O-acetylhydroquinone (IC(50)=2.5 microM/l) suppressed the proliferation
      of murine B16F10 melanoma cells with a potency much greater than those of
      farnesol (IC(50)=45 microM/l) and farnesyl anthranilate (IC(50)=46 microM/l), its
      alcohol, and ester counterparts with proven anti-tumor activities in vivo.
      Geranyl-O-acetylhydroquinone (IC(50)=5.1 microM/l) also had a much-improved
      activity compared to geraniol (IC(50)=160 microM/l) and geranyl anthranilate
      (IC(50)=30 microM/l). The suppression by farnesyl-O-acetylhydroquinone was
      concentration- and time-dependent and was accompanied by arrest of cell cycle at
      G1 and G2/M phases as shown by flow cytometry. Farnesyl-O-acetylhydroquinone and
      lovastatin had additive impact on B16 cell proliferation. Farnesyl-O
      acetylhydroquinone also suppressed the proliferations of human cancer cells HL
      60, DU145, PC-3, LNCaP, Caco-2, and A549. Our results suggested that farnesyl
      derivatives, suppressors of tumor 3-hydroxy-3-methylglutaryl coenzyme A reductase
      activities, have potential as chemopreventive or chemotherapeutic agents.

PMID- 14643449
TI  - Association between glutathione S-transferase M1 and T1 polymorphisms and
      increased risk for bladder cancer in Korean smokers.
AB  - We evaluated the relationship between polymorphisms in the GSTM1 and GSTT1 genes
      and smoking status in a case-controlled study of a Korean population. The GSTM1
      and GSTT1 genotypes were determined using a polymerase chain reaction (PCR)-based
      method and prognostic factors, such as staging and grading were evaluated for 126
      bladder cancer patients, and 204 control subjects. Smoking represented a high
      risk factor (odds ratio (OR)=4.8, 95% confidence interval (CI)=2.9-8.0) for the
      patients with bladder cancer. The frequency of GSTM1 null individuals was higher
      than in the controls, but the differences were not statistically significant
      (OR=1.56, 95% CI=2.9-8.0). For Korean subjects who smoked more than 1 pack of
      cigarettes per year (PPY), the increased risk of bladder cancer was associated
      with the GSTM1 null genotype (OR=0.5, 95% CI=0.3-0.9). Low-stage bladder tumors
      were more common among the GSTM1 null genotypes (OR=2.3; 95% CI=1.1-5.5). This
      study suggests that in Korean subjects the GSTM1 null genotype may be associated
      with increased risk for bladder cancer, in a manner that appears to depend upon
      smoking status. And also, in bladder cancer patients the GSTM1 null genotype
      appears to be associated with a poorer prognosis with low stage bladder tumors.

PMID- 14643450
TI  - Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL
      tyrosine phosphatases.
AB  - Human PRL-1, PRL-2, and PRL-3 tyrosine phosphatases induce the malignant
      transformation of epithelial cells. We tested the hypothesis that the oncogenic
      effects of PRL occur by increasing cellular proliferation. Cells stably
      transfected with PRL-1 or PRL-2 exhibited 2.7-3.3-fold increases over control
      cells in the rate of DNA synthesis and the proportion of cells in S-phase, and
      they progressed more rapidly from G1 into S. In addition, cells overexpressing
      either PRL-1 or PRL-2 exhibited enhanced cyclin-dependent kinase 2 (CDK2)
      activity and significantly lower p21(Cip1/Waf1) protein levels, and PRL-1
      overexpressing cells had higher cyclin A protein levels than control cells. We
      conclude that PRL phosphatases increase cell proliferation by stimulating
      progression from G1 into S phase, and this process may be dependent on the down
      regulation of the cyclin dependent kinase inhibitor p21(Cip1/Waf1).

PMID- 14643451
TI  - Over-expression of wild-type Securin leads to aneuploidy in human cells.
AB  - Changes in gene expression and aneuploidy are both common features of cancers and
      under- or over-expression of single genes can cause aneuploidy. Securin, which is
      involved in chromatid separation, has transforming activity in vitro and is over
      expressed in many tumours. We have used a GFP-based assay for chromosome loss in
      human cells to investigate the effects of over-expressing Securin. We find that
      over-expression causes a two-fold increase in chromosome loss rate and can thus
      be a direct cause of aneuploidy.

PMID- 14643452
TI  - Isolation of lung tumor specific peptides from a random peptide library:
      generation of diagnostic and cell-targeting reagents.
AB  - Discovery of ligands specific to receptor(s) on a surface of a cancer cell could
      impact clinical issues including functional diagnosis and cell-specific drug
      delivery. Using a phage display approach, we have isolated 20-mer peptide ligands
      that bind to 3 different human lung tumor cell lines, NCI-H1299, NCI-H2009, and
      A549. The panning protocol is unbiased with no selection pressure towards binding
      a particular cellular receptor. The isolated phage bind to their target cells 24
      300 times better than a control phage. Furthermore, the isolated peptides display
      remarkable cell-specificities and are able to discriminate between normal and
      cancerous cells as well as different lung tumor cells. The cell-specificities are
      not coincident with tumor classes indicating that the peptides are able to
      recognize cell-surface features that are not represented within the
      classification of tumor type. The isolated peptides are functional outside of the
      context of the phage and multimerization of the peptide increases its affinity
      for its given cell type, thus expanding their utility in clinical situations.

PMID- 14643453
TI  - Human papillomavirus DNA in sera of cervical cancer patients as tumor marker.
AB  - Persistent infection with human papillomavirus (HPV) has been widely recognized
      to induce carcinoma of the uterine cervix. Viral DNA has been documented to occur
      as tumor DNA in the circulation of patients with primary tumors caused by viral
      infection. The aim of this study was to evaluate the utility of serum HPV DNA as
      tumor marker in cervical cancer patients. Sera taken from 94 cervical cancer
      patients at the date of diagnosis and follow-up serum samples from 24 patients
      were examined for HPV DNA using PCR enzyme immunoassay. Serum samples taken at
      the date of diagnosis were HPV DNA positive in 45% of all investigated samples.
      Sera which were HPV DNA positive at the time of diagnosis became and also
      remained negative after primary treatment in patients without recurrence or
      persistent disease. HPV DNA was positive up to 423 days before the time of
      clinical diagnosis of recurrence in 10 out of 13 cases (median 72 days, range 0
      423 days). Serum HPV DNA seems to reflect biological activity of the tumor. Our
      results indicate that serum HPV DNA might be a useful additional marker for early
      detection of recurrence in cervical cancer patients.

PMID- 14643454
TI  - The rodent prefrontal cortex.

PMID- 14643455
TI  - Do rats have a prefrontal cortex?
AB  - The lack of a single anatomical or functional definition of 'prefrontal cortex'
      has led to different and, in some respects, controversial views on the existence
      of a prefrontal cortex in non-primate mammals, in particular in rats. Until the
      classic paper by Rose and Woolsey [Res. Publ. Assoc. Nerv. Ment. Dis. 27 (1948)
      210], the general idea was that a prefrontal cortex is unique to primate species.
      Rose and Woolsey's 'prefrontal cortex' definition was based upon a single
      anatomical criterion, i.e. the cortical projection area of the mediodorsal
      thalamic nucleus. Single criteria, however, do not appear to be sufficient for
      defining the prefrontal cortex. Therefore, other anatomical and functional
      characteristics are currently used to identify the prefrontal cortex in different
      species. Yet, recently the debate about the nature of the prefrontal cortex in
      non-primate species has been resumed. In the present paper we will compare the
      structural and functional characteristics of the prefrontal cortex of nonhuman
      primates and rats. We will argue that rats have a functionally divided prefrontal
      cortex that includes not only features of the medial and orbital areas in
      primates, but also some features of the primate dorsolateral prefrontal cortex.

PMID- 14643456
TI  - A systems approach to orbitofrontal cortex function: recordings in rat
      orbitofrontal cortex reveal interactions with different learning systems.
AB  - The recognition that certain aspects of prefrontal function can be effectively
      modeled in rats has led to a slow expansion of interest in rat prefrontal cortex
      over the past decade. One of the most promising of these model systems is the
      orbitofrontal cortex of the rat. Rat orbitofrontal cortex is anatomically similar
      to the orbital prefrontal region in primates, and this similarity is borne out by
      behavioral and neurophysiological findings. Here we will present data on
      orbitofrontal cortex function from a number of parallel studies from our
      laboratories that employed single unit recording techniques to probe neural
      encoding in rat orbitofrontal cortex and related parts of the amygdala and the
      hippocampal memory systems. Together, these reports and associated behavioral
      studies suggest that the orbitofrontal region, in both rats and primates, is
      specialized to integrate concrete and abstract sensory constructs with
      information regarding the incentive value of associated outcomes to guide or
      modulate behavior. To the extent that monkey prefrontal function can model
      certain aspects of human prefrontal function, we argue that this model can now be
      extended to the rat orbitofrontal cortex. In addition, we argue that the function
      of orbitofrontal cortex needs to be considered in terms of its interactions with
      other brain systems.

PMID- 14643457
TI  - Did a change in sensory control of skilled movements stimulate the evolution of
      the primate frontal cortex?
AB  - The classical view of the evolution of such skilled movements as use of the hand
      and digits for reaching and grasping posited that these movements had their
      origin in the primate lineage. The hypothesis was that the permissive influence
      of adaptations to an arboreal environment led to the evolution and elaboration of
      these skills. Associated with skilled movements were increases in the size of the
      frontal lobe, temporal lobe, and cerebellum and the elaboration of new
      connections between these structures and other cortical regions, the brainstem,
      and spinal cord. The classical view saw rodents as phylogenetically old and
      relatively unrelated animals, displaying no skilled movements, and whose normal
      repertoire of behavior had little dependence on the frontal lobes. Here, evidence
      is reviewed that shows that the classical view of the origins of skilled
      movements is incorrect. Skilled movements are phylogenetically old, evolved in
      relation to food handling, and are especially well developed in rodents.
      Behavioral evidence also shows that the skilled movements of rodents are
      dependent upon the function of the frontal cortex. Nevertheless, there are
      difference in the sensory control of skilled movement in primates and rodents.
      Skilled movements are largely directed by vision in primates but are directed by
      hapsis/olfaction in rodents. This difference in sensory control suggests that at
      a dividing point between primates and rodents, there was a profound
      behavior/brain transformation. Primates retained the skilled movements
      exemplified in rodents, but brought these movements under visual control.
      Correspondingly, along with many other anatomical changes, the primate frontal
      cortex became relatively larger and move complex under visual influence.

PMID- 14643458
TI  - What the rodent prefrontal cortex can teach us about attention
      deficit/hyperactivity disorder: the critical role of early developmental events
      on prefrontal function.
AB  - The present review surveys a broad range of findings on the functions of the
      rodent prefrontal cortex (PFC) in the context of the known pathophysiology of
      attention-deficit/hyperactivity disorder (ADHD). An overview of clinical findings
      concludes that dysfunction of the right PFC plays a critical role in ADHD and
      that a number of early developmental factors conspire to increase the risk of the
      disorder. Rodent studies are described which go far in explaining how the core
      processes which are deficient in ADHD are mediated by the PFC and that the
      mesocortical dopamine (DA) system plays a central role in modulating these
      functions. These studies also demonstrate a surprising degree of cerebral
      lateralization of prefrontal function in the rat. Importantly, the PFC is highly
      vulnerable to a wide variety of early developmental insults, which parallel the
      known risk factors for ADHD. It is suggested that the regulation of physiological
      and behavioral arousal is a fundamental role of the PFC, upon which many "higher"
      prefrontal functions are dependent or at least influenced. These right
      hemispheric arousal systems, of which the mesocortical DA system is a component,
      are greatly affected by early adverse events, both peri- and postnatally.
      Abnormal development, particularly of the right PFC and its DAergic afferents, is
      suggested to contribute directly to the core deficits of ADHD through
      dysregulation of the right frontostriatal system.

PMID- 14643459
TI  - Recovery from infant medial frontal cortical lesions in rats is reversed by
      cortical lesions in adulthood.
AB  - Previous studies have shown that when the medial prefrontal cortex (mPFC) is
      removed at 7-10 days of age there is a spontaneous filling of the lesion cavity
      and a nearly complete restitution of behaviour. In the current study animals
      received mPFC lesions on postnatal day 10 and on day 160 the tissue occupying the
      mPFC region was again removed. Behavioural performance on the Morris water task
      was compared to animals with either only day 10 mPFC lesions or only day 160 mPFC
      lesions. Rats with the combined day 10 and day 160 lesions or day 160 lesions
      were severely impaired at the task whereas the rats with only day 10 lesions
      showed complete recovery. An analysis of dendritic arborization in pyramidal
      neurons adjacent to the lesion showed increased dendritic arborization in the
      basilar fields in both the P10 groups but this was not associated with functional
      recovery in the animals with the two mPFC lesions. It thus appears that the
      tissue that filled in the mPFC lesions on day 10 was functional.

PMID- 14643460
TI  - C-fos activation patterns in rat prefrontal cortex during acquisition of a cued
      classical conditioning task.
AB  - The prefrontal cortex (PFC) is known to be involved in associative learning;
      however, its specific role in acquisition of cued classical conditioning has not
      yet been determined. Furthermore, the role of regional differences within the PFC
      in the acquisition of cued conditioning is not well described. These issues were
      addressed by exposing rats to either one or four sessions of a cued classical
      conditioning task, and subsequently examining c-fos immunoreactivity in various
      areas of the PFC. Differences in patterns of c-fos immunopositive nuclei were
      found when comparing the PFC areas examined. No significant differences were
      found between rats presented with a temporally contingent conditioned stimulus
      (CS) light and food (paired groups) and those presented with the same stimuli
      temporally non-contingently (unpaired groups). In lateral and orbital PFC, both
      the paired and unpaired groups showed more c-fos immunopositive nuclei than
      control groups exposed only to the behavioral setup (context exposed groups), and
      all groups showed a drop in c-fos immunopositive nuclei from session 1 to session
      4. In dorsal medial PFC, no differences were seen between the paired, unpaired
      and context exposed groups. These groups did, however, differ from naive animals,
      an effect that was not seen in the ventral medial PFC. The results of this study
      do not support a role for the PFC in the acquisition of a cued classical
      conditioning task. The differences seen between paired, unpaired and context
      exposed groups in orbital and lateral PFC could be due to contextual conditioning
      or reward-related effects.

PMID- 14643461
TI  - Learning-related changes in response patterns of prefrontal neurons during
      instrumental conditioning.
AB  - A crucial aspect of organizing goal-directed behavior is the ability to form
      neural representations of relationships between environmental stimuli, actions
      and reinforcement. Very little is known yet about the neural encoding of response
      reward relationships, a process which is deemed essential for purposeful
      behavior. To investigate this, tetrode recordings were made in the medial
      prefrontal cortex (PFC) of rats performing a Go-NoGo task. After task
      acquisition, a subset of neurons showed a sustained change in firing during the
      rewarded action sequence that was triggered by a specific visual cue. When these
      changes were monitored in the course of learning, they were seen to develop in
      parallel with the behavioral learning curve and were highly sensitive to a switch
      in reward contingencies. These sustained changes correlated with the reward
      associated action sequence, not with sensory or reward-predicting properties of
      the cue or individual motor acts per se. This novel type of neural plasticity may
      contribute to the formation of response-reinforcer associations and of behavioral
      strategies for guiding goal-directed action.

PMID- 14643462
TI  - Behavioral and paired-pulse facilitation analyses of long-lasting depression at
      excitatory synapses in the medial prefrontal cortex in mice.
AB  - Accumulative evidence indicates that acute (before extinction) and long-lasting
      (during extinction) depression can occur at excitatory synapses in mouse medial
      prefrontal cortex (mPFC) during re-exposure to a tone (conditioned stimulus: CS),
      previously paired with footshock (unconditioned stimulus: US). As recently shown,
      the long-term depression (LTD)-like plasticity in the mPFC does not interfere
      with extinction of CS-evoked freezing but predicts spontaneous recovery of this
      fear response. Here, the objectives were to investigate: (i). whether a
      resistance to extinction without any prefrontal acute synaptic plasticity could
      produce LTD-like changes, and (ii). by the use of paired-pulse facilitation (PPF)
      analyses, whether pre- or post-synaptic mechanisms were involved in this LTD
      phenomenon. Preliminary analyses indicated that levels of acute depression did
      not correlate with the degree of fear acquisition (effects of number of CS-US
      pairings). As a consequence, mice conditioned with 2CS+ or 2CS+/2CS- (partial
      reinforcement of the CS known to induce resistance to extinction) exhibited CS
      associated freezing without any acute synaptic depression in the mPFC. However,
      during further CS-alone presentations, the 2CS+/2CS- group developed LTD-like
      changes that accompanied their resistance to extinguish freezing to the CS. In
      contrast, the 2CS+ group normally extinguished their conditioned freezing with
      synaptic transmission remaining at baseline levels. PPF analyses revealed that
      facilitation was unchanged following prefrontal LTD. These data, combined with
      our previous findings, (i). support a critical involvement of prefrontal LTD-like
      changes in spontaneous recovery of fear responses, and (ii). suggest a post
      synaptic site for these changes.

PMID- 14643463
TI  - Orbital prefrontal cortex mediates reversal learning and not attentional set
      shifting in the rat.
AB  - It has been demonstrated previously that lesions to medial prefrontal cortex in
      rats impair the shifting of attentional set between perceptual features of
      complex stimuli [J. Neurosci. 20 (2000) 4320], a result that mirrors the deficit
      found in humans and monkeys [Nature 380 (1996) 69; Behav. Neurosci. 110 (1996)
      872; J. Neurosci. 17 (1997) 9285; Neuropsychologia 29 (1991) 993]. These data
      imply functional homology between rat medial prefrontal cortex and primate
      prefrontal cortex.In marmoset monkeys, there is a double dissociation between the
      effects of lesions of lateral prefrontal cortex, which impair shifting of
      attentional set, and lesions of orbital prefrontal cortex, which result in
      impairments of reversal of stimulus-reward contingencies, leaving attentional set
      shifting capacities intact [Nature 380 (1996) 69; Behav. Neurosci. 110 (1996)
      872; J. Neurosci. 17 (1997) 9285]. The present investigation examined whether
      lesions to rat orbital prefrontal cortex would produce deficits in reversal
      learning in the absence of deficits in shifting attentional set, as seen in
      monkeys. Rats were trained to perform an attentional set-shifting task that is
      formally the same as that used in monkeys and humans. In a single session, rats
      performed a series of discriminations, including acquisitions and reversals.
      Damage to orbital prefrontal cortex in the rats did not disrupt the ability to
      acquire, maintain or shift attentional set. We report here the same selective
      impairment in reversal learning in rats as seen in primates with orbital
      prefrontal cortex lesions.

PMID- 14643464
TI  - Dissociable aspects of performance on the 5-choice serial reaction time task
      following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal
      cortex in the rat: differential effects on selectivity, impulsivity and
      compulsivity.
AB  - It is becoming increasingly apparent that multiple functions of the frontal
      cortex such as inhibitory control and executive attention are likely sustained by
      its functionally distinct and interacting sub-regions but the precise
      localization of dissociable executive processes has proved difficult and
      controversial. In the present series of studies, we investigated the behavioural
      effects of bilateral excitotoxic lesions of different regions of the rat
      neocortex in the 5-choice serial reaction time task. Whereas lesions of the
      dorsal anterior cingulate cortex (ACC) impaired performance of the task as
      revealed by a reduction in discriminative accuracy, lesions made to distinct
      ventral regions of the frontal cortex showed selective deficits in inhibitory
      measures of control. Specifically, the infralimbic lesion produced increases in
      premature responding that was accompanied by fast response latencies. By
      comparison, the orbitofrontal lesion showed perseverative tendencies particularly
      when the inter-trial interval was made long and unpredictable, a challenge that
      would normally promote premature responding instead. These different behavioural
      effects following dorsal and ventral lesions of the rodent frontal cortex
      signifies the integrity of the frontal cortex in multiple executive mechanisms
      that work independently and complementarily by which performance is optimized.
      Furthermore, these data provide new insights into the functional organization of
      the rodent frontal cortex with a particular emphasis on localization of function.

PMID- 14643465
TI  - Ventral medial prefrontal cortex and emotional perseveration: the memory for
      prior extinction training.
AB  - Several years ago, we found that lesions of ventral medial prefrontal cortex
      (mPFCv) disrupted performance during the extinction component of a classical fear
      conditioning task without affecting acquisition performance. We called this
      emotional perseveration, hypothesizing that mPFCv may normally act to inhibit
      fear responses to a conditioned stimulus (CS) when the CS no longer signals
      danger. Subsequent studies have supported this hypothesis, showing that mPFCv is
      crucial for the memory of prior extinction training. The present study examined
      the effects of mPFCv lesions made after training. Such lesions resulted in
      reduced freezing to contextual stimuli and normal responding to the CS presented
      alone during a retention test. Rats were then subjected to extinction trials (CS
      without US) over multiple days. In contrast to pre-training lesions, post
      training lesions had little effect on extinction rate. All rats were given
      additional training. Lesioned rats expressed greater fear reactions than
      controls, indicating that prior extinction was less effective in them. Lesioned
      rats also showed resistance to extinction during reextinction trials, confirming
      our earlier finding that lesions made before training weaken the effectiveness of
      extinction trials. These results suggest three conclusions. First, an intact
      mPFCv during acquisition may protect the animal from prolonged responding during
      extinction trials following brain insult. Second, changes in mPFCv may predispose
      subjects toward enhanced fear reactions that are difficult to extinguish when
      reexposed to fearful stimuli, due to a diminished capacity to benefit from the
      fear-reducing impact of prior extinction experience. Third, contextual cues
      processed by mPFCv may influence extinction performance.

PMID- 14643466
TI  - Lesions of the medial prefrontal cortex or nucleus accumbens core do not impair
      inhibitory control in rats performing a stop-signal reaction time task.
AB  - The 'stop-signal' task measures the ability to inhibit a response that has
      already been initiated, i.e. the ability to stop. Human subjects who have been
      classified as 'impulsive', for example, those with attention
      deficit/hyperactivity disorder (ADHD), are slower to react to the stop signal,
      and are often less sensitive to changes in the timing of signals to stop. Imaging
      studies have implicated fronto-striatal circuitry in the mediation of this form
      of response control. We report inhibition functions on the stop-signal reaction
      time (SSRT) task for normal rats, and following damage to the medial prefrontal
      cortex or to the nucleus accumbens core. Neither group of excitotoxic lesions
      produced significant deficits on task performance. Subsequent treatment with D
      amphetamine (0.3 and 1.0mg/kg) resulted in quicker go-trial reaction times (mRT)
      overall, but had no significant effect on SSRT. Neither medial prefrontal cortex
      nor nucleus accumbens lesions had any differential effects on performance
      following D-amphetamine. These results are discussed with respect to the fronto
      striatal circuitry involved in the mediation of behavioural inhibition.

PMID- 14643467
TI  - The role of prelimbic cortex in instrumental conditioning.
AB  - Numerous studies have implicated human and primate prefrontal cortex in the
      ability to hold and manipulate goal or outcome-related information in working
      memory to guide the performance of forthcoming actions. Here we report that cell
      body lesions of prelimbic cortex impair the ability of rats to select an action
      based on previously encoded action-outcome associations. Rats were food deprived
      and trained to press two levers, one delivering food pellets and the other a
      sucrose solution. All rats acquired the lever-press response although the initial
      acquisition in the prelimbic rats was significantly slower than in sham controls.
      Furthermore, whereas in sham-lesioned rats, post-training devaluation of one of
      the two outcomes using a specific satiety procedure produced a selective
      reduction in performance on the lever that in training delivered the prefed
      outcome, prelimbic rats failed to show a selective devaluation effect and
      appeared to reduce performance on both levers non-selectively. Importantly, this
      impairment only emerged in extinction; in subsequent experiments it was found
      that, when a specific action-outcome association was cued either by presentation
      of the outcome itself or by presenting a stimulus previously paired with the
      outcome, rats demonstrated an ability to select the associated action. These
      results suggest that action-outcome encoding may be intact in prelimbic rats and
      that the lesion impaired their ability to retain this learning in working memory
      in order to establish a course of action. Alternatively, the lesion may have
      altered the relative contribution of action-outcome and outcome-action
      associations to instrumental performance. On this account, prelimbic lesions
      affect action-outcome encoding but leave outcome-action associations intact
      providing the basis for outcome-mediated initiation of an action sufficient,
      perhaps, to support acquisition and performance in the lesioned rats.

PMID- 14643468
TI  - The role of the prefrontal cortex in object-place learning: a test of the
      attribute specificity model.
AB  - In order to test an attribute specificity model of prefrontal cortex function,
      rats with lesions in the prelimbic-infralimbic (PL-IL) or anterior cingulate and
      precentral (AC-PC) subregions of the medial prefrontal cortex and controls were
      trained on an object-place paired associate task. Rats with AC-PC lesions
      acquired the task as readily as controls. In contrast, the PL-IL lesioned rats
      did not learn the task. Whenever higher order processing is required to solve a
      task, the data support an attribute-specificity model of prefrontal cortex
      function in that the PL-IL cortices support both object and place attribute
      information in a variety of tasks including object-place paired associate
      learning.

PMID- 14643469
TI  - Inactivation of the infralimbic prefrontal cortex reinstates goal-directed
      responding in overtrained rats.
AB  - Over the course of extended training, instrumental responding in rats shows a
      transition from goal-dependent performance to goal-independent performance, as
      assessed by sensitivity to reward-devaluation induced by taste aversions or
      specific satiety. It has been suggested that this reflects the gradual dominance
      of reflexive, habit-based responding over voluntary, goal-directed actions.
      Previous research suggests that lesions of the medial prefrontal cortex disrupt
      this interaction between goal-directed and habitual responding. More
      specifically, whereas lesions of the prelimbic prefrontal cortex appear to
      disrupt normal goal-directed responding, lesions of the infralimbic prefrontal
      cortex cause animals to remain goal-directed even after substantial overtraining.
      The current experiment explored further the nature of this interaction between
      actions and habits. Rats were given extended training of an instrumental lever
      press response before bilateral intracerebral cannulae giving access to the
      infralimbic cortex were implanted. Following further reminder training all
      animals were given a test of goal sensitivity by specific-satiety devaluation of
      the instrumental outcome, or a matched reward, prior to extinction tests. Before
      these tests, half of the animals received bilateral infusions of muscimol into
      the infralimbic cortex, and the remainder, control vehicle infusions. As expected
      after extended instrumental training, control-infused animals showed habitual
      performance that was not selectively influenced by devaluation of the
      instrumental outcome. In contrast, animals receiving temporary inactivation of
      the infralimbic cortex by muscimol showed selective sensitivity to devaluation of
      the instrumental outcome, indicating a reinstatement of goal-directed responding
      in these animals. This suggests that the development of habitual responding
      reflects the active inhibition of goal-directed responses that are mediated by
      action-outcome associations.

PMID- 14643470
TI  - Thyroglossal duct cysts: presentation and management in children versus adults.
AB  - OBJECTIVES: To determine if the clinical presentation of thyroglossal duct cysts
      (TGDC) varies between children and adults and whether this knowledge helps
      optimize the surgical management. METHODS: We retrospectively identified all
      patients with TGDC managed in our department between 1992 and 2002. We reviewed
      the patients' charts and recorded their gender, age at diagnosis, clinical
      presentation, radiologic imaging, surgical management, post-operative
      complications, and recurrence rate and compared the variables between the
      children and adults. RESULTS: Twenty-one children and 41 adults were treated for
      TGDC. Of the children, 57% were male and 43% were female, whereas 49% of the
      adults were male and 51% were female (P = 0.53). The average age was 6 +/- 5
      years in children and 45 +/- 16 years in adults, which demonstrates a bimodal
      distribution. Forty-three percent of children and 42% of adults presented with an
      infected neck mass (P > 0.99). Among our patients, 96% of the adults and 100% of
      the children underwent a Sistrunk operation. Four children developed a wound
      infection that resolved with antibiotics. One adult developed a haematoma and
      another developed a wound seroma. There was one recurrence among adults and one
      among children, both of whom were treated with a second Sistrunk procedure.
      CONCLUSIONS: There appears to be a bimodal distribution for age at presentation
      of TGDC. Since the differential diagnosis among adults is broader, the
      opportunity for misdiagnosis is greater. However, once the correct diagnosis is
      made, the surgical management and post-operative outcome between adults and
      children is the same.

PMID- 14643471
TI  - Are some septal deformities inherited? Type 6 revisited.
AB  - OBJECTIVE: There has been little research into inherited septal deformities.
      While, Pejic carried out a study some 50 years ago, and Grymer more recently
      suggested that some posterior septal deformities could be inherited, both studies
      lack a precise definition of the types of septal deformities which were
      investigated. The aim of this paper is to investigate the hypothetic influence of
      heredity on the onset of particular types of septal deformities. The authors
      investigated a very particular and well defined type of septal deformity: type 6
      after Mladina's classification. METHODS: The authors studied a group of 22
      children among 779 children aged 7-14, selected at random, suffering from type 6
      septal deformity and their 44 parents. They were examined by means of anterior
      rhinoscopy by two the same ENT specialists in rhinology. The control group
      consisted of 24 children with a straight nasal septum of the same age and sex
      distribution and their 48 parents. The results were compared using Fisher's exact
      probability test. RESULTS: In the studied group type 6 septal deformity was found
      in 21 out of 22 both fathers and mothers of these children. Type 6 was not found
      in any of 48 parents of children with no septal deformity. CONCLUSIONS: There is
      a high positive correlation between the appearance of type 6 septal deformities
      in both mothers and fathers of children with this type of deformity. The high
      correlation in the incidence of type 6 nasal deformity in mothers and their
      children and in fathers and their children suggests that this type of nasal
      deformity is inherited. Most authors hold that only posterior septal deformities
      result from inheritance factors, while anterior deformities result from
      environmental factors, that is, from injury to the nose and the central massif of
      the face. However, our study of type 6 deformities shows that certain types of
      anterior deformities can be inherited.

PMID- 14643472
TI  - The development of sphenoid sinus in Asian children.
AB  - OBJECTIVES: (1) To study the developmental changes of sphenoid sinus in Asian
      children and (2) to test the hypothesis that the sphenoid sinus may be developing
      slower in Asian, by comparing the growth patterns between Asian and Caucasian
      children. MATERIALS AND METHODS: Review of MR imaging of the skull of 220 Asian
      children less than 15 years of age in a tertiary hospital. The results were
      compared to a representative Caucasian study by Szolar et al. [Surg. Radiol.
      Anat., 16 (1994) 193]. RESULTS: Grade 1 sphenoid was present in all children less
      than 6 months old. Conversion from marrow to fat of the sphenoid sinus (Grade 2)
      began at 7 months and was present in patients up to 6 years old. Signs of
      pneumatization (Grade 3) of the sphenoid sinus were first noted in patients at 10
      months old. Almost 100% pneumatization was seen in all the children after 6 years
      old except for one child with Grade 1 sphenoid at 11 years old. Compared to
      Caucasian children, there was a significantly higher proportion of Grade 3 cases
      in Asian children from 0 to 4 years of age (P = 0.05). No difference in the
      distribution of cases was noted from 4 to 8 years (P = 0.466) and 8-15 years (P =
      1.00). CONCLUSION: The developmental changes of the sphenoid sinus in Asian
      children were determined and found to be similar when compared to Caucasian
      children. The findings did not support the hypothesis that the Asian sphenoid
      sinus is developing slower compared to that of the Caucasians.

PMID- 14643473
TI  - Adenoid tissue rhinopharyngeal obstruction grading based on fiberendoscopic
      findings: a novel approach to therapeutic management.
AB  - OBJECTIVE: A grading into four classes of hypertrophied adenoid rhinopharyngeal
      obstructions in children on the basis of fiberendoscopic findings to outline an
      effective therapeutic program according to this classification. METHODS: Ninety
      eight children with chronic nasal obstruction and oral respiration were examined
      by anterior rhinoscopy, and fiberendoscopy. During the investigation, the
      fiberendoscopic images of the choanal openings were divided into four segments
      from the upper choanal border to the nasal floor. In view of clinical findings,
      78 patients also underwent active anterior rhinomanometry. RESULTS: In eight
      patients (8.2%), the fiberendoscopic imaging revealed that the adenoid tissue
      occupied only the upper segment in the rhinopharyngeal cavity (< 25%). Therefore,
      choanal openings were free (first degree obstructions). In 20 patients (20.4%),
      the adenoid tissue was confined to the upper half (< 50%) of the rhinopharyngeal
      cavity (second degree obstructions) and in 63 patients (64.3%) the tissue
      extended over the rhinopharynx (< 75%) with obstruction of choanal openings and
      partial closure of tube ostium (third degree obstructions). Only in seven cases
      (7.14%), the obstruction was almost total. As a consequence, both the tube ostium
      and the lower choanal border could not be observed (fourth degree obstructions).
      CONCLUSIONS: In the first two classes of obstructions, characterized by moderate
      or discrete adenoid hypertrophy, adenoidectomy should not be performed. In these
      conditions, the causes of possible nasal obstructions are usually due to either
      dysmorphic, allergic or phlogistic pathologies. For the fourth degree adenoid
      obstructions, surgery is always recommended. The most important therapeutic
      problems occur in the third degree obstructions which include most patients who
      suffered from hypertrophied adenoids. Moreover, the therapeutic strategy can be
      conditioned not only by nasal respiratory difficulties but also by frequent
      concomitant complications such as otitis, sinusitis, sleep apnea, etc. These
      disorders may be caused by both nasal obstruction and/or phlogistic problems
      (adenoiditis).

PMID- 14643474
TI  - Early stage impacts of tonsillectomy on immune functions of children.
AB  - OBJECTIVE: The purpose of this study was to investigate the changes in the
      humoral and cellular immunity of patients with chronic tonsillitis before and 1
      month after tonsillectomy. PATIENTS AND METHODS: 37 patients scheduled for
      tonsillectomy were enrolled in this study. The levels of CD3+, CD4+, CD8+, CD19+,
      CD25+ and CD16+ + 56+ were measured for cellular immunity, and levels of IgG,
      IgA, IgM, C3 and C4 were measured for humoral immunity in blood samples taken
      from these patients before and 1 month after the operation. RESULTS: The levels
      of CD3+, CD8+ and CD19+ were reduced in post-operative period as compared to pre
      operative period but this was not statistically significant (P > 0.05). However
      it was found that the level of CD4+ was significantly increased while the level
      of CD25+ was reduced (P < 0.05) in the post-operative period. There were
      statistically significant differences between pre- and post-operative levels of
      immunoglobulins, C3 and C4, which were decreased after tonsillectomy (P < 0.05),
      but these levels were comparable with those of the control group. CONCLUSION: The
      results from the present study indicate that humoral and cellular immunity of
      patients undergoing tonsillectomy were decreased in the early period and came to
      normal later. The cellular and humoral immune responses are stimulated in
      patients with tonsillitis, and tonsillectomy removes this stimulus without
      negatively affecting the patient's immune functions.

PMID- 14643476
TI  - Prognostic factors of recidivism in pediatric cholesteatoma surgery.
AB  - OBJECTIVE: To analyze the results on a series of pediatric cholesteatomas, using
      various preoperative factors, including some of the proposed classification
      systems, to identify those factors that influence the postoperative result.
      METHOD: Retrospective review of 118 children with acquired cholesteatoma who
      underwent surgery from January 1978 to October 1999. The median observation
      period was 5 years, range 1-20 years. The rate of recidivism calculated using the
      Kaplan-Meier method and relative risk by the Cox regression model. RESULTS:
      Cholesteatoma in patients less than 8 years old with mastoid involvement had
      significantly higher risk of recidivism than the other groups examined.
      CONCLUSIONS: In this study, cholesteatoma recurred up to 5 years after operation,
      and long-term close follow-up is important especially in cases involving higher
      risk such as younger child with mastoid extension of cholesteatoma.

PMID- 14643475
TI  - Microbiology of otorrhea in children with tympanostomy tubes: implications for
      therapy.
AB  - OBJECTIVE: Based on the prevalence of children with tympanostomy tubes who
      develop otorrhea, an analysis was performed to identify specific prognostic
      indicators in this population to enable clinicians to determine the likelihood of
      specific pathogens and select the best empiric therapy. METHODS: Data from two
      multicenter clinical trials of ofloxacin otic solution 0.3% (OFLX) trials in
      pediatric patients 1-12 years of age were used to develop a statistical model to
      predict the likelihood of external auditory canal (EAC) or nasopharyngeal (NPG)
      pathogens. Data were available for 283 microbiologically evaluable patients.
      Potential indicators included subject age, season of enrollment, ear aspiration,
      cleaning, otorrhea, and granulation tissue. The model used a stepwise logistic
      regression analysis relating the occurrence of NPG or EAC pathogens to the
      potential prognostic indicators. RESULTS: Among the total study population, 42.8
      and 61.5% had NPG and EAC pathogens, respectively; 10.6% had both. The most
      frequently isolated valid pathogens were Streptococcus pneumoniae and Haemophilus
      influenzae. Significant prognostic indicators for NPG pathogens were subject age,
      season of enrollment, and presence of ear odor. Although these indicators were
      similar for EAC and NPG pathogens, the correlation was reversed, i.e. older
      subjects had EAC pathogens, and younger ones (< 2 years) had NPG pathogens; EAC
      pathogens were associated with presence of ear odor and NPG pathogens, with
      absence of ear odor. CONCLUSIONS: A statistically and clinically valid model has
      been developed that has prognostic value for the clinician treating children with
      otorrhea and tympanostomy tubes and serves as an aid in the appropriate choice of
      empiric therapy.

PMID- 14643477
TI  - GJB2 gene mutations causing familial hereditary deafness in Turkey.
AB  - Mutations in Connexin 26 (Cx26) play an important role in autosomal non-syndromic
      hereditary hearing loss. In this study, our objective was to find out the
      significance of Cx26 mutations in Turkish families who had hereditary deafness.
      Fourteen families who had at least two prelingually deaf children per family were
      included in the study. One affected child from each of the 14 families was
      selected for single-stranded conformational polymorphism SSCP analysis. Three PCR
      reactions were used for each subject to amplify the entire Cx26 coding region
      with overlap. PCR products were sequenced on an Applied Biosystems (ABI) model
      3700 automated sequencer. Six of the 14 representative family members (42.9%)
      demonstrated shifts on SSCP and were subsequently sequenced for Exons 1 and 2 of
      GJB2 and were tested for the 432 kb upstream deletion. No mutations were found in
      Exon 1 and no 432 kb deletions were noted. Three different GJB2 mutations were
      found in Exon 2 of the probands, which were 35delG, 299-300delAT, and 487G > A
      (M163V). GJB2 mutations were detected in 21.4% of the families. Two patients were
      homozygous for 35delG and 299-300delAT mutations, and were given a diagnosis of
      DFNB1 deafness (14.3%). Two different polymorphisms, 457G > A (V153I) and 380G >
      AG (R127H) were also found. In conclusion, although GJB2 mutations were detected
      in 21.4% of the families tested, only 14.3% of subject representatives were
      homozygous and therefore deafness caused by Cx26 mutation segregated with DFNB1.
      Thus, contribution of GJB2 mutations appears less significant in familial
      deafness. This necessitates further assessment for the other known gene regions
      as well as a search for new genetic factors in familial type of genetic deafness.

PMID- 14643478
TI  - Anxiety and depression in mothers of speech impaired children.
AB  - OBJECTIVE: In the adult population, anxiety and depression are the most frequent
      emotional disorders. In cases when mothers of speech impaired children are
      affected by these disorders may significantly influence the development of the
      child. The purpose of this study was to assess the prevalence of anxiety and
      depression in mothers of speech impaired children as literature provides only
      little information on this topic. METHODS: Hundred mothers (age 33.4 +/- 5.3
      years, range: 22-47 years) of 100 preschool children (32 girls, 68 boys; age 4.2
      +/- 1.5 years, range 1;3-7;7 years) with a speech impairment were investigated.
      Children with cochlear hearing loss, syndromes or other developmental disorders
      were excluded from the study. To estimate the prevalence of anxiety disorders and
      depression in the mothers the German version of the Hospital Anxiety and
      Depression Scale (HADS) was used. Data from 157 healthy women from the German
      test manual served as controls. Microsoft Excel and Matlab software packages were
      used for description, analysis, and evaluation. The differences in prevalence
      rates were tested by chi2-test and Wilcoxon's rank sum test. RESULTS: Assessed by
      the HADS-depression subscale 11% of the mothers of speech impaired children met
      criteria for depression compared to 2.5% in the control group. The prevalence in
      the study group was significantly higher (P < 1%). The prevalence of anxiety
      disorders did not differ from normative data on a significant level (P > 5%).
      CONCLUSIONS: Screening mothers of speech impaired children for depression is of
      significant clinical interest. For this purpose, the HADS is a suitable test.
      Further studies are necessary to investigate the influence of speech impairment
      and its development on the severity and development of mothers' depression. Up to
      now, no data exist about how fathers of speech impaired children react
      emotionally, so this question has to be focused on in future.

PMID- 14643479
TI  - Magnetic nasal foreign bodies: a result of fashion mania.
AB  - The fashion of body piercing among adults has encouraged children to have similar
      procedures or imitate them by applying small magnets to sustain the jewelery used
      in piercing in position [Emerg. Med. J. 19 (2002) 71]. We present cases of
      children who have placed magnets on their nasal alae that became misplaced on to
      the nasal septum causing severe pain and in some cases nasal bleeding and septal
      perforation. We describe management of these cases.

PMID- 14643480
TI  - Facial nerve anomalies in association with congenital hearing loss.
AB  - OBJECTIVE: Facial nerve (FN) anomalies are exceedingly rare. The association
      between a hearing loss and an anomalous facial nerve has never been touched
      deeply in the literature. The aim of this study is to report facial nerve
      anomalies in patients presenting with congenital hearing loss (COHL) and/or
      facial nerve palsy. METHODS: A retrospective chart review over 10 years from two
      academic tertiary referral centers. Eight patients were diagnosed with facial
      nerve anomalies in association with congenital hearing loss. The age ranged from
      7 months to 13 years. RESULTS: Five patients had conductive congenital hearing
      loss (CCHL). Two had congenital sensorineural hearing loss (CSNHL). The eighth
      patient had a mixed hearing loss (MHL). Surgical findings for patients with
      conductive congenital hearing loss included facial nerve passing inferior to oval
      window (OW) (two patients), facial nerve covering head of stapes (three
      patients), deformed stapes (two patient), deformed incus (two patient), and
      absent incus (one patient). Radiological findings for patients with congenital
      sensorineural hearing loss and mixed hearing loss include, single cavity anomaly
      (one patient), dilated vestibule and superior semicircular canal (one patient),
      and absent internal auditory canal (IAC) (two patients). For patients with
      conductive congenital hearing loss, the radiological findings consistency
      demonstrates a soft tissue opacification in the middle ear. CONCLUSIONS:
      Congenital hearing loss may be associated with facial nerve anomalies. Pediatric
      otolaryngologists should be cautious when exploring patients with conductive
      congenital hearing loss.

PMID- 14643481
TI  - The use of injectable collagen in the management of pediatric vocal unilateral
      fold paralysis.
AB  - Vocal fold paralysis (VFP) is the second most common congenital abnormality that
      affects the larynx. Unilateral cases may be asymptomatic or feature symptoms
      related to laryngeal incompetence, such as aspiration and dysphonia. Management
      has traditionally been conservative as a high percentage of these paralyses
      recover spontaneously. The literature is scant on the acute or chronic management
      of unilateral vocal fold paralysis related symptoms in children. We present a
      series of four children (age 21 days, 5 years, 5 years, and 18 years) with
      unilateral VFP paralysis treated with collagen (Cymmtera) augmentation for
      control of symptoms related to laryngeal incompetence. Two children (age 21 days
      and 5 years) were managed in the acute setting. Follow-up has ranged from 4 to 12
      months, and all have maintained excellent outcomes. Vocal fold augmentation with
      collagen is an effective therapeutic option in the management of symptoms related
      to unilateral VFP and laryngeal incompetence. It decreases the risk of aspiration
      and improves vocal quality. Collagen augmentation can be used in the acute
      setting to decrease aspiration, possibly avoiding a tracheotomy or gastrostomy
      tube placement, or to augment patients with a tracheotomy who are still severely
      aspirating.

PMID- 14643482
TI  - Localized cervical neuroblastoma: prevention of surgical complications.
AB  - OBJECTIVES: The purpose of this study focused on cervical neuroblastoma (NB) was
      to assess the prognosis, define the most suitable methods of investigation, and
      evaluate risk factors for complications following primary surgery. METHODS:
      Between 1990 and 1999, we conducted two consecutive prospective multicentric
      studies (NBL90 and NBL94) on localized NB. Because the first study (1990-1994)
      found surgery-related morbidity and mortality, several surgical risk factors
      (i.e. adhesion to major vessels, size, friability, and dumb bell tumor) were
      defined and used prospectively as criteria of resectability in the second study
      (1994-1999). RESULTS: Of 617 cases included in the two studies, 43 involved
      cervical NB including 17 cervicothoracic tumors. With a median follow-up of 4
      years, overall survival and event-free survival rates were 91 and 81%,
      respectively with no significant difference between cervical or cervicothoracic
      NB. Seventeen patients were included in the second study; surgery was used as the
      first line treatment in 11. Full pre-operative work-up was performed in eight
      patients, demonstrating one or more risk factors in three. The remaining three
      patients underwent emergency surgery with no pre-operative work-up or only
      ultrasound: two developed serious complications. All three patients presenting
      documented risk factors developed post-operative complications versus only two of
      the eight patients who presented no risk factor (n = 5) or were inadequately
      evaluated (n = 3) (P = 0.06). None of the five patients in whom full work-up
      demonstrated no risk factor had post-operative complications (P = 0.02).
      CONCLUSIONS: Cervical neuroblastoma has a favorable prognosis. Surgery is the
      treatment of choice but there is a risk of complications. Appropriate pre
      operative work-up is mandatory to evaluate resectability. The surgical risk
      factors defined for our second study seem to be significant predictors of post
      operative complications.

PMID- 14643483
TI  - The Bcl-2 protein expression in germinal centers of hypertrophied adenoids in
      children.
AB  - The aim of this study was to evaluate Bcl-2 expression in the germinal centers of
      adenoid in children on the assumption that it can be treated as a marker of
      adenoidal tissue function. The study involved 95 children. The patients were
      divided into three age groups: aged up to 5, 5-10 and above 10 years. The
      analysed material were adenoids removed on the grounds of hypertrophy.
      Immunohistochemical analyses were carried out using monoclonal antibodies
      (DAKO/Bcl-2, No. M0887) directed against human Bcl-2 protein. The presence of Bcl
      2 positive lymphocytes within the lymphoid follicles and Bcl-2 immunostaining
      were scored. The immunohistochemical staining showed Bcl-2 positive lymphocytes
      in the examined sections of adenoidal tissue and their characteristic location,
      mainly within the mantle zone. Bcl-2 reactivity was widespread in hyperplastic
      lymphoid tissue, including germinal centers surroundings, scattered cells within
      the germinal centers and the T-cell areas in general. We have not found
      statistically significant correlation between Bcl-2 expression and clinical
      status and change in Bcl-2 expression level according to age. The apoptosis
      presence within the germinal centers and its lack in mantle zone, the
      manifestation of which is Bcl-2 expression, is a sign of a proper lymphocytes
      maturation within lymphoid follicles. It seems that these processes are not
      influenced by age, so the adenoid involution is probably associated with the
      changes in the number of lymphoid follicles rather than change or inhibition of
      the processes that take place in them.

PMID- 14643484
TI  - Thyroid abscess at an adolescent age.
AB  - We report a case of thyroid abscess in a 17-year-old girl. She was presented with
      swelling and pain in the region of the left thyroid lobe. The diagnosis was
      confirmed by ultrasonography and fine needle aspiration. After incision,
      evacuation of the pus and antibiotic treatment manifestations of disease
      disappeared. Barium swallow did not prove any hypopharyngeal fistula. The girl is
      now without any problems for 3 years. The patient had infectious mononucleosis 2
      months prior development of the thyroid abscess. We contemplate that it may had
      changed the immunological state that facilitated this rare inflammation.

PMID- 14643485
TI  - Congenital pharyngolaryngeal band: report of an unusual case of respiratory
      distress.
AB  - Congenital pharyngolaryngeal band (PLB) is an extremely rare congenital
      abnormality, characterized by a fibrous web extending from the nasopharynx to the
      epiglottis. We report a case of unilateral pharyngolaryngeal band in a new-born
      who presented severe airway obstruction and feeding difficulties. The band
      extended from the right postero-inferior part of the nasopharynx to the right
      lateral margin of the larynx. Faucial pillars and tonsil were absent on this
      side. Endoscopic and radiological assessments excluded associated cervicofacial
      abnormality. Two endoscopic laser resection procedures were necessary to liberate
      the larynx from PLB. Clinical and radiological assessment advocated a second
      pharyngeal pouch development failure as the origin to PLB.

PMID- 14643486
TI  - Tuberculosis of zygoma.
AB  - A case of tubercular osteomyelitis of zygoma is reported. It is difficult to
      diagnose because of its rarity unless a high index of suspicion is kept in mind
      more so in an endemic area.

PMID- 14643488
TI  - Hairpin formation in DNA computation presents limits for large NP-complete
      problems.
AB  - Recently, several DNA computing paradigms for NP-complete problems were
      presented, especially for the 3-SAT problem. Can the present paradigms solve more
      than just trivial instances of NP-complete problems? In this paper we show that
      with high probability potentially deleterious features such as severe hairpin
      loops would be likely to arise. If DNA strand x of length n and the 'complement'
      of the reverse of x have l match bases, then x forms a hairpin loop and is called
      a (n,l)-hairpin format. Let gamma=2l/n. Then gamma can be considered as a
      measurement of the stability of hairpin loops. Let p(n,l) be the probability that
      a n-mer DNA strand is a (n,l)-hairpin format, and q(n,l)((m)) be the probability
      that m ones are chosen at random from 4(n) n-mer oligonucleotides such that at
      least one of the m ones is a (n,l)-hairpin format. Then, q(n,l)((m))=1-(1
      p(n,l))(m)=mp(n,l). If we require q(n,l)((m))<a, where a<1, then m<ln(1-a)/ln(1
      p(n,l))=a/p(n,l). It means that we can only solve the instances of size m of NP
      complete problems. Clearly the greater p(n,l), the smaller m, and the smaller a
      the smaller m. In this paper, we show p(n,l) is high. Therefore, the present DNA
      computing paradigms cannot solve large NP-complete problems. For example, if
      n=20, used in Adleman and Lipton's paradigm, gamma=50% and a=50%, then m is
      almost 12.

PMID- 14643489
TI  - The loss of self-boundaries: towards a neuromolecular theory of schizophrenia.
AB  - I start out with the hypothesis that the basic symptoms of schizophrenia are
      caused by a loss of self-boundaries. Phenomenologically, schizophrenic symptoms
      are based on the inability of the brain to delimit conceptual boundaries. At the
      cellular level in the brain, I have in previous work attributed a spatio-temporal
      boundary setting function to the glial cells such that glial cells determine the
      grouping of neurons into functional units. Mutations in genes that result in non
      splicing of introns can produce aberrant versions of neurotransmitter receptors
      that lack protein domains encoded by entire exons and can also have protein
      sequence encoded by introns that have not been properly spliced out. I propose
      that such "chimeric" receptors are generated in glial cells and that they cannot
      interact properly with their cognate neurotransmitters. The glia will then lose
      their inhibitory function with respect to the information processing within
      neuronal networks. The loss of glial boundary-setting may result in a
      'borderless' generalization of information processing such that the structuring
      of the brain in functional domains is almost completely lost. This loss of glial
      boundary setting could be an explanation of the loss of self-boundaries in
      schizophrenia.

PMID- 14643490
TI  - Could a "philosophical fitness landscape" foster Wilsonian consilience in
      biosystems debates?
AB  - A digital interpretation of Edward O. Wilson's principle of "consilience"
      knowledge will grow out of interdisciplinary accommodation-is attempted by
      modeling it with 32 pixels on a "philosophical fitness landscape" (PFL). This
      approach partially answers a need expressed by Wilson to develop useful
      consilience methodology, including maps and other orientation devises. Responding
      also to his call for more imagination, a "virtual roundtable" discussion is
      convened among 13 scientific luminaries to debate the meaning of biological life
      and its origin. This is done to test (subjectively) the null hypothesis that a
      PFL would be insensitive to the diversity of perspectives engaged in such a
      debate. Rejecting the null hypothesis, an argument is made that an appropriate
      PFL might help to foster Wilsonian consilience in biosystems debates, where it is
      needed most.

PMID- 14643491
TI  - Genetic network inference: the effects of preprocessing.
AB  - Clustering of gene expression data and gene network inference from such data has
      been a major research topic in recent years. In clustering, pairwise measurements
      are performed when calculating the distance matrix upon which the clustering is
      based. Pairwise measurements can also be used for gene network inference, by
      deriving potential interactions above a certain correlation or distance
      threshold. Our experiments show how interaction networks derived by this simple
      approach exhibit low-but significant-sensitivity and specificity. We also explore
      the effects that normalization and prefiltering have on the results of methods
      for identifying interactions from expression data. Before derivation of
      interactions or clustering, preprocessing is often performed by applying
      normalization to rescale the expression profiles and prefiltering where genes
      that do not appear to contribute to regulation are removed. In this paper,
      different ways of normalizing in combination with different distance measurements
      are tested on both unfiltered and prefiltered data, different prefiltering
      criteria are considered.

PMID- 14643492
TI  - Constructive effects of fluctuations in genetic and biochemical regulatory
      systems.
AB  - Biochemical and genetic regulatory systems that involve low concentrations of
      molecules are inherently noisy. This intrinsic stochasticity has received
      considerable interest recently, leading to new insights about the sources and
      consequences of noise in complex systems of genetic regulation. However, most
      prior work was devoted to the reduction of fluctuation and the robustness of
      cellular function with respect to intrinsic noise. Here, we focus on several
      scenarios in which the inherent molecular fluctuations are not merely a nuisance,
      but act constructively and bring about qualitative changes in the dynamics of the
      system. It will be demonstrated that in many typical situations biochemical and
      genetic regulatory systems may utilize intrinsic noise to their advantage.

PMID- 14643493
TI  - A study on the interplay between energy and matter transformation: the effect of
      elevated temperatures on the leaf morphology of Vitis vinifera var. Merlot.
AB  - This investigation explores the relationship between increased energy levels and
      leaf morphology. It tests the idea that the causal agent of development is the
      dissipation of energy into transformed matter. The energy under which leaves
      developed was modified by increasing temperatures in grape cordons through
      wrapping them in clear plastic sleeves in the early spring. At the higher
      temperatures, and energy levels, there was a small but statistically significant
      decrease in leaf size and a change in organization the leaves. The decrease in
      leaf size may be due to a reallocation of resources, either to greater shoot
      growth as a previous study demonstrated or to the appearance of more vectors of
      development in the leaves, i.e. the appearance of more developmental subsystems.
      The leaves that grew under the higher temperature regime were more complex,
      perhaps indicating that the grapes on those same vines may produce more complex
      juice, another expression of more developmental subsystems. The change in
      organization in these leaves that developed at higher temperature argues that the
      causal agent in plant development is energy dissipation and the concomitant
      transformation of matter, the latter expressed in the appearance of more growth
      vectors.

PMID- 14643494
TI  - Solving the set cover problem and the problem of exact cover by 3-sets in the
      Adleman-Lipton model.
AB  - Adleman wrote the first paper in which it is shown that deoxyribonucleic acid
      (DNA) strands could be employed towards calculating solutions to an instance of
      the NP-complete Hamiltonian path problem (HPP). Lipton also demonstrated that
      Adleman's techniques could be used to solve the NP-complete satisfiability (SAT)
      problem (the first NP-complete problem). In this paper, it is proved how the DNA
      operations presented by Adleman and Lipton can be used for developing DNA
      algorithms to resolving the set cover problem and the problem of exact cover by 3
      sets.

PMID- 14643495
TI  - Highly sensitive gas chromatographic determination of ethanol in human urine
      samples.
AB  - In order to evaluate recent alcohol consumption, a very sensitive and specific
      gas chromatographic method for ethanol determination in human urine samples was
      developed. The non-invasive method was performed without any pretreatment and
      carried out on a Stabilwax capillary column, 30 m x 0.53 mm x 1.0 microm film
      thickness. Helium was used as carrier gas with a constant inlet pressure of 27.72
      kPa (0.277 bar) and a flame ionization detector (FID). Quantification was
      performed with the use of acetonitrile as an internal standard (IS). The
      calibration curve was linear throughout the concentration range from 0.5 to 500
      mg/l. The calculated intra- and inter-day coefficients of variation were below
      8%. A clear chromatographic separation of ethanol from methanol, acetone, 1
      propanol and 2-propanol was achieved.

PMID- 14643496
TI  - Measurement of carvedilol in plasma by high-performance liquid chromatography
      with electrochemical detection.
AB  - Carvedilol is a beta/alpha1-adrenoceptor blocker. A sensitive method for
      measuring plasma levels of carvedilol in human administrated low doses is needed
      since its plasma concentration is low. We measured carvedilol and carvedilol M21
      aglycon using high-performance liquid chromatography (HPLC) with electrochemical
      detection. The amperometric detector was operated at 930 mV versus Ag/AgCl. Mean
      coefficients of variation (n = 5) for carvedilol and M21-aglycon were 4.0 and
      7.7% (intra) and 6.1 and 6.7% (inter), respectively. The lower limit of
      quantification for each analyte was 0.10 ng/ml (signal-to-noise ratio = 3). This
      lower limit of quantification for carvedilol was sufficient for clinical use.

PMID- 14643497
TI  - Simple liquid chromatography method for the rapid simultaneous determination of
      prednisolone and cortisol in plasma and urine using hydrophilic lipophilic
      balanced solid phase extraction cartridges.
AB  - This article describes the development and validation of a simple solid phase
      extraction (SPE) and HPLC method for the extraction and the specific
      determination of prednisolone and hydrocortisone (cortisol) in both plasma and
      urine using one washing step with Oasis hydrophilic lipophilic balanced (HLB)
      cartridges (1 ml/30 mg, 30 microm). Recoveries of prednisolone and cortisol from
      plasma and urine exceeded 82%. The limit of quantification (LOQ) in plasma and
      urine was 9.9 and 6.7 ng/ml for cortisol, respectively, and 11.6 and 8.0 ng/ml
      for prednisolone, respectively. The intraday and interday precision (measured by
      CV%) for both prednisolone and cortisol in both plasma and urine was always less
      than 7%. The accuracy (measured by relative error %) for both prednisolone and
      cortisol in both plasma and urine was always less than 8%. The advantages of the
      developed method are the use of a one step washing SPE utilising HLB cartridges
      which do not suffer the drying out problems of conventional SPE cartridges and
      the time saving when compared with solvent extraction (SE), in addition to the
      simultaneous determination of prednisolone and cortisol in both plasma and urine.

PMID- 14643498
TI  - Determination of metformin in plasma using a new ion pair solid phase extraction
      technique and ion pair liquid chromatography.
AB  - This article describes the development of the first ion pair solid phase
      extraction technique (IPSPE), which has been applied to the extraction of
      metformin from plasma samples. In addition an ion pair chromatographic method was
      developed for the specific HPLC determination of metformin. Several extraction
      and HPLC methods have been described previously for metformin, however, most of
      them did not solve the problems associated with the high polarity of this drug.
      Drug recovery in the developed method was found to be more than 98%. The limit of
      detection and limit of quantification was 3 and 5 ng/ml, respectively. The
      intraday and interday precision (measured by coefficient of variation, CV%) was
      always less than 9%. The accuracy (measured by relative error, R.E.%) was always
      less than 6.9%. Stability analysis showed that metformin is stable for at least 3
      months when stored at -70 degrees C. The method has been applied to 150 patient
      samples as part of a medication adherence study.

PMID- 14643499
TI  - Measurement of total mirtazapine and normirtazapine in plasma/serum by liquid
      chromatography with fluorescence detection.
AB  - A simple high performance liquid chromatography (HPLC) method for the measurement
      of the new antidepressant mirtazapine and its N-demethyl metabolite,
      normirtazapine, in human plasma or serum during low dose mirtazapine therapy has
      been developed. A Waters Spherisorb S5 SCX column was used with ammonium
      perchlorate (50 mmol/l) in methanol/water (95 + 5 (v/v)), apparent pH 6.7, as
      eluent, and fluorescence detection. Only small volumes of sample (0.2 ml) and
      extraction solvent are used. An interference study found no significant co
      elution with drug or metabolite, although paroxetine co-elutes with the internal
      standard. The recovery of mirtazapine and normirtazapine (mean +/- S.D.) was 79
      +/- 2, and 64 +/- 3%, respectively. The LOD was estimated as 0.5 microg/l, LLOQ
      was 1 microg/l, with a linear response over the concentration range 4-1000
      microg/l (both analytes). The analytes were stable in serum for at least 10
      months when stored at -20 degrees C. Intra- and inter-day accuracy were in the
      range 91-107 and 93-103%, respectively. In clinical samples (n = 14, median
      mirtazapine dose 45 mg per day, range 15-45 mg per day) the median (range)
      mirtazapine and normirtazapine concentrations were 26 (8-40) and 21 (8-32)
      microg/l, respectively.

PMID- 14643500
TI  - Chromatographic determination of the association constant between 8
      methoxypsoralen and modified beta-cyclodextrin: protective effect of
      hydroxypropyl-beta-cyclodextrin on 8-methoxypsoralen toxicity in human
      keratinocytes.
AB  - The retention of 8-methoxypsoralen (8-MOP) on an immobilised hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) column was analysed in HPLC by the determination of its
      Langmuir distribution isotherm. A such method was used to confirm the potential
      drug complexing role of this cyclodextrin. The 8-MOP/HP-beta-CD association
      constant (K) was equal to 29.5 and 18.7 M-1, respectively, at a temperature equal
      to 5 and 25 degrees C, respectively. These association constant values were used
      to determine the cytotoxicity profile of human keratinocyte cell line (HaCaT) in
      relation to the complex concentration. It was showed through these data that HP
      beta-CD had a cytoprotective since a reverse effect of HP-beta-CD on 8-MOP
      cytotoxicity was observed.

PMID- 14643501
TI  - Determination of 8-methoxypsoralen in human plasma, and microdialysates using
      liquid chromatography-tandem mass spectrometry.
AB  - The validation of a LC/MS/MS method for the determination of 8-methoxypsoralen (8
      MOP) in human plasma and microdialysates after topical application is described.
      Plasma samples were extracted by liquid-liquid extraction with diisopropylether
      using 4,5',8-trimethylpsoralen (TMP) as internal standard. Chromatographic
      separation of plasma sample extracts was carried out using a short narrow-bore
      Nucleosil C18 column (30 mm x 2.0 mm i.d.) with acetonitrile/(2 mM ammonium
      acetate buffer, 2 mM acetic acid) (80:20, v/v). For mass spectrometric analysis
      an API 3000 triple quadrupole mass spectrometer was employed. The mass
      transitions used were m/z 217.2-->174.0 for 8-MOP and m/z 229.1-->142.1 for TMP.
      Microdialysis samples diluted with an equal amount of acetonitrile did not
      require any extraction and were analyzed directly on a narrow-bore Nucleosil C18
      column (70 mm x 2.0mm i.d.) with acetonitrile/(2 mM ammonium acetate buffer, 2 mM
      acetic acid) (50:50, v/v) with the mass transition m/z 217.2-->174.0. The assays
      were validated over the concentration ranges of 0.5-50 ng/ml for plasma samples
      and 0.25-50 ng/ml for microdialysates, respectively.

PMID- 14643502
TI  - Simultaneous detection of arginine, asymmetric dimethylarginine, symmetric
      dimethylarginine and citrulline in human plasma and urine applying liquid
      chromatography-mass spectrometry with very straightforward sample preparation.
AB  - Nitric oxide (NO) is synthesized by NO synthase from L-arginine, which can be
      competitively blocked by endogenous inhibitors such as asymmetric
      dimethylarginine (ADMA), but not by symmetric dimethylarginine (SDMA). ADMA is
      degraded by dimethylarginine dimethylaminohydrolase (DDAH) to dimethylamine and
      citrulline. A growing number of published clinical studies documented a strong
      correlation between increased ADMA blood levels and cardiovascular morbidity and
      mortality. We present here a highly sensitive method for the determination of
      this compounds in plasma and urine by means of HPLC-MS. The sample preparation is
      very simple and comprises only protein precipitation and concentration in the
      case of plasma samples and dilution in the case of urine. The samples are
      derivatized automatically with orthophthaldialdehyde and 2-mercaptoethanol, are
      separated on a 250 mm x 4 mm RP18 column by gradient elution with formate
      buffer/methanol and are detected by ESI-MS. The calibration functions are linear
      and cover the range from normal to pathologic concentration values of the
      analytes. The intra-day relative standard deviation (R.S.D.) of the assay for
      ADMA in plasma is 7.5% and the corresponding inter-day R.S.D. is 5.7%. In urine,
      these values for ADMA are 3.8 and 6.4%, respectively. All other analytes in
      plasma as well as in urine exhibit intra-day R.S.D. below 8%. The corresponding
      inter-day R.S.D. are all below 13%.

PMID- 14643503
TI  - Identification of 2,5-dimethoxy-4-ethylthiophenethylamine and its metabolites in
      the urine of rats by gas chromatography-mass spectrometry.
AB  - A simple and specific method based on gas chromatography-selected ion monitoring
      mass spectrometry (GC-SIM-MS) for the analysis of in vivo metabolism of 2,5
      dimethoxy-4-ethylthiophenethylamine (2C-T-2) in rats is described. Three male
      rats were administered 20 mg/kg of 2C-T-2 by intra-peritoneal injection, and 24 h
      urine fractions were collected before and after the administration for analysis.
      After acidic hydrolysis of the urine samples, the metabolites were liquid-liquid
      extraction and analyzed by a quadruple mass spectrometer in the selected ion
      monitoring mode. The findings show that four metabolites of 2-(4-ethylthio-2,5
      dimethoxyphenyl)-ethanol (Mw: 242), 4-ethylthio-2,5-dimethoxyphenyl acetic acid
      (Mw: 256), 1-acetoamino-2-(2-hydroxy-4-ethylthio-5-methoxyphenyl)-ethane (Mw:
      269) and 1-acetoamino-2-(2-methoxy-4-ethylthio-5-hydroxyphenyl)-ethane (Mw: 269)
      are present and the metabolic pathway for 2C-T-2 in the rat is proposed.

PMID- 14643504
TI  - Development and validation of a gas chromatography-mass spectrometry assay for
      hair analysis of amphetamine, methamphetamine and methylenedioxy derivatives.
AB  - A procedure based on gas chromatography-mass spectrometry (GC-MS) is described
      for the determination of amphetamine, methamphetamine, 3,4
      methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA,
      ecstasy), 3,4-methylenedioxyethylamphetamine (MDE or MDEA) and N-methyl-1-(3,4
      methylenedioxyphenyl)-2-butanamine (MBDB) in hair. Hair samples were digested
      with 1 M sodium sulfide at 37 degrees C (by shaking for 3 h and was kept at room
      temperature overnight), and extracted with two sequential extraction procedures:
      liquid-liquid extraction with tert-butyl methyl ether and solid-phase extraction
      with Bond-Elut Certify columns. Extracted analytes were derivatised with N-methyl
      bis(trifluoroacetamide), separated by a 5% phenylmethylsilicone column and
      determined by a mass spectrometer detector in selected ion monitoring mode. A
      good reproducibility (intra-assay R.S.D.=1.5-15.7%), accuracy (intra-assay error
      = 2.0-11.7%) and sensitivity (LOD=0.03-0.08 ng/mg hair) were attained. The method
      was successfully applied to the analysis of the proximal (1 cm) hair segment to
      assess recent self-reported use in "ecstasy" consumers. Otherwise, further
      studies are needed to validate methodology developed in case of amphetamine
      consumption.

PMID- 14643505
TI  - Simultaneous determination of triflusal and its major active metabolite, 2
      hydroxy-4-trifluoromethyl benzoic acid, in rat and human plasma by high
      performance liquid chromatography.
AB  - A rapid, selective and sensitive high-performance liquid chromatography (HPLC)
      method was developed and validated for the simultaneous determination of
      triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic
      acid (HTB), in rat and human plasma. HPLC analysis was carried out using a 5
      microm particle size, C18-bonded silica column and acetonitrile-methanol-water
      (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was
      used as the internal standard. The method involved extraction with an
      acetonitrile-chloroform mixture (60:40, v/v) and evaporation to dryness with
      nitrogen stream. The chromatograms showed good resolution and sensitivity and no
      interferences by plasma constituents. The mean absolute recovery for human plasma
      was 93.5 +/- 4.2% for triflusal and 98.5 +/- 3.1% for HTB. The lower limits of
      quantification of triflusal and HTB in human plasma were 20 and 100 ng/ml,
      respectively. The calibration curves in human plasma were linear over the
      concentration range 0.02-5.0 microg/ml for triflusal and 0.1-200.0 microg/ml for
      HTB with correlation coefficients greater than 0.999 and with inter- or intra-day
      coefficients of variation (CV) not exceeding 10.0%. This assay procedure was
      applied to the study of metabolite pharmacokinetics of triflusal and HTB in rat
      and human.

PMID- 14643506
TI  - Metabolism of verapamil: 24 new phase I and phase II metabolites identified in
      cell cultures of rat hepatocytes by liquid chromatography-tandem mass
      spectrometry.
AB  - Verapamil is a widely prescribed calcium antagonist, but suffers from extensive
      first pass metabolism. Despite its frequent use in drug metabolism a complete
      understanding of its metabolic pathway is still lacking. We thus investigated
      verapamil's metabolism in cultures of primary rat hepatocytes and isolated
      metabolites from cell culture media by solid phase extraction (SPE). In detail,
      we investigated their structure in multiple liquid chromatography-mass
      spectrometry (LC-MSn) experiments and found 25 phase I and 14 phase II
      metabolites. We showed many metabolites to be produced by oxidative dealkylation,
      and several yet unknown metabolites were identified that stem from hydroxylation
      and dealkylation reactions. Furthermore, we identified an array of glucuronides
      and, additionally, a glucoside. Finally, we investigated the enantioselective
      biotransformation of verapamil and found preferential metabolism of the S
      enantiomers. In conclusion, this illustrates again the true complexity of
      verapamil's disposition.

PMID- 14643507
TI  - Enantiomeric determination of the plasma levels of omeprazole by direct plasma
      injection using high-performance liquid chromatography with achiral-chiral column
      switching.
AB  - A direct injection high-performance liquid chromatographic (HPLC) method, with
      column-switching, for the determination of omeprazole enantiomers in human plasma
      is described. A restricted access media (RAM) of bovine serum albumin (BSA) octyl
      column has been used in the first dimension for separation of the analyte from
      the biological matrix. The omeprazole enantiomers were eluted from the RAM column
      onto an amylose tris(3,5-dimethylphenylcarbamate) chiral column by the use of a
      column-switching valve and the enantioseparation was performed using acetonitrile
      water (60:40 v/v) as eluent. The analytes were detected by their UV absorbance at
      302 nm. The validated method was applied to the analysis of the plasma samples
      obtained from 10 Brazilian volunteers who received a 40 mg oral dose of racemic
      omeprazole and was able to quantify the enantiomers of omeprazole in the clinical
      samples analyzed. The assay was able to determine the cytochrome P450 2C19
      phenotype of the subjects participating in this study.

PMID- 14643508
TI  - Glycosylation study of the major genetic variants of human alpha1-acid
      glycoprotein and of their pharmacokinetics in the rat.
AB  - Human alpha1-acid glycoprotein (AAG) is a mixture of at least two genetic
      variants, the A variant and the F1 and/or S variant or variants, which are
      encoded by two different genes. AAG is also an extensively glycosylated protein
      which possesses five N-linked glycans exhibiting substantial heterogeneity in
      their structures. The first objective of this study was to investigate the
      glycosylation of the two major gene products of AAG, i.e. the A variant and a
      mixture of the F1 and S variants (F1*S). To this end, we combined a
      chromatographic method for the fractionation of the AAG variants with a lectin
      binding assay to characterise the glycosylation of purified glycoproteins.
      Secondly, because the oligosaccharides can influence the disposition of AAG, a
      kinetic study of the AAG variants was carried out in the rat. After intravenous
      administration of whole human AAG, the separation and quantification of the AAG
      variants in plasma was performed by application of specific methods by
      isoelectric focusing and immunonephelometry. The binding studies carried out on a
      panel of lectins showed significant differences in the lectin-binding
      characteristics of the separated F1*S and A variants, accounting for differences
      in the degree of branching of their glycan chains and substitution with sialic
      acid and fucose. The plasma concentration-time profiles of the F1*S and A
      variants were biphasic, and only small differences were observed between the
      variants for their initial and terminal half-lives, clearance and distribution
      volume. This indicates that the structural differences between the two AAG gene
      products do not affect their pharmacokinetics in the rat. Specific drug transport
      roles have been previously demonstrated for the F1*S and A variants, calling for
      further investigations into their effects on the disposition of drugs they bind
      in plasma. The present study shows that such investigations are possible without
      being complicated by kinetic differences between these variants.

PMID- 14643509
TI  - High-performance liquid chromatographic mass spectrometric method for the
      determination of ursodeoxycholic acid and its glycine and taurine conjugates in
      human plasma.
AB  - A novel sensitive high-performance liquid chromatography-electrospray mass
      spectrometry method has been developed for the determination of ursodeoxycholic
      acid (UDCA) and its glycine and taurine conjugates, glycoursodeoxycholic acid
      (GDCA) and tauroursodeoxycholic acid (TDCA). The procedure involved a solid phase
      extraction of UDCA, GDCA, TDCA and the internal standard, 23-nordeoxycholic acid
      from human plasma on a C18 Bond Elut cartridge. Chromatography was performed by
      isocratic reverse phase separation with methanol/25 mM ammonium acetate (40/60,
      v/v) containing 0.05% acetic acid on a C18 column with embedded polar functional
      group. Detection was achieved using an LC-MS/MS system. The standard curve was
      linear over a working range of 10-3000 ng/ml for all analytes and gave an average
      correlation coefficient of 0.9992 or better during validation. The absolute
      recovery for UDCA, GDCA, TDCA and the internal standard was 87.3, 83.7, 79.5 and
      95.8%, respectively. This method is simple, sensitive and suitable for
      pharmacokinetics, bioequivalence or clinical studies.

PMID- 14643510
TI  - Development of a capillary electrophoresis method for the determination of
      allopurinol and its active metabolite oxypurinol.
AB  - A simple and sensitive capillary zone electrophoresis method with UV absorbance
      detection is described for the quantitation of allopurinol and its metabolite
      oxypurinol in aqueous solution. The influence of different parameters on
      migration times, peak symmetry, efficiency and resolution was systematically
      investigated; these parameters included the nature and concentration of the
      separation buffer, pH and applied voltage. A buffer consisting of 15 mM 2-[N
      cyclohexylamino]ethanesulfonic acid (CHES) adjusted to pH 8.8 was found to
      provide a very efficient and stable electrophoretic system for the analysis of
      these compounds. The optimized method was validated with respect to precision,
      linearity, limits of detection and quantification, accuracy and robustness. The
      applicability of the assay was demonstrated by analyzing these compounds in serum
      and allopurinol in commercial pharmaceutical preparations.

PMID- 14643511
TI  - Automated solid-phase extraction and liquid chromatographic method for retinoid
      determination in biological samples.
AB  - In this study, a method for partly automated sample preparation and fully
      automated solid-phase extraction method for plasma, kidney and liver samples for
      various retinoids like all-trans-4-oxo-retinoic acid, 13-cis-4-oxo-retinoic acid,
      13-cis-retinoic acid, 9-cis-retinoic acid, all-trans-retinoic acid, retinol and
      retinyl palmitate was established. Plasma, embryo-, kidney-and liver-homogenates
      were automatically mixed and extracted on multiple usage solid-phase (C2)
      extraction cartridges immediately before HPLC analysis. Automated cleaning,
      preconditioning and incorporation of the loaded cartridge to fully automated HPLC
      separation and quantification of the various retinoids in a single HPLC run was
      established. The recovery of the retinoids was generally between 80 and 90%.
      Intra-day repeatability was < 11.7%. As little as 1.2 ng/ml could be quantified
      in lipid-mixture standard samples. This method allows a highly automated sample
      preparation and a fully automated solid-phase extraction with good selectivity
      for the study of endogenous retinoids and retinoids after nutritional
      supplementations and pharmacological applications in several biological samples.

PMID- 14643512
TI  - Two different clean-up procedures for liquid chromatographic determination of
      ochratoxin A in urine.
AB  - This paper describes two different procedures for extraction of ochratoxin A
      (OTA) from urine samples: one using acidic chloroform-methanol mixture, followed
      by solid-phase extraction (SPE) clean-up and the other using commercial Chem Elut
      columns and a chloroform-formic acid mixture. The recovery of OTA using the
      procedure with silica gel columns was 82% with a R.S.D. < 8.4% and the detection
      and quantitation limits were 0.5 and 1.5 ng OTA/ml, respectively. The recovery of
      OTA in the second procedure with urine samples purified only on commercial Chem
      Elut columns was 95% with R.S.D. < 4.0%, and detection and quantitation limits
      0.3 and 0.9 ng/ml, respectively. Both procedures of OTA extraction effectively
      eliminate interfering substances and give reliable and repeatable results.
      However, the procedure with Chem Elut columns gave higher recovery and lower
      detection and quantitation limits. It was successfully applied in determining OTA
      in human urine samples.

PMID- 14643513
TI  - Separation and purification of phosphatidylcholine and phosphatidylethanolamine
      from soybean degummed oil residues by using solvent extraction and column
      chromatography.
AB  - Natural phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were separated
      and purified from soybean degummed oil residues in this work. Crude PC and PE
      were first separated from degummed oil residues by extraction with 95% ethanol,
      and then the crude PC and PE were used as raw materials to prepare high purity PC
      and PE by using column chromatography of silica gel (100-200 mesh) with different
      eluents and elution modes. The high purity PC (content > 90%) was obtained from
      the crude PC by using isocratic elution with methanol as eluent. Compared with
      the methods reported by using isocratic elution with mixed solvents as eluent or
      gradient elution, the procedure proposed exhibits low cost and industry
      potentialities because of some advantages, such as operation simplicity, cheap
      equipment and solvent to be recovered easily. The purity of the PE product
      prepared from the crude PE was more than 75%. The gradient elution was preferable
      to isocratic elution for reducing the elution time and eluent consumption when to
      prepare PE from the crude PE. The effects of loading amount and the flow-rate on
      separation efficiency were also investigated. For obtaining high separation
      efficiency, the loading amount should be less than 2.0 g crude PC or PE/100 g
      silica gel, and the flow-rate should be controlled under 4 ml/min for crude PC
      and 3 ml/min for crude PE, respectively.

PMID- 14643514
TI  - Toxicological detection of the new designer drug 1-(4-methoxyphenyl)piperazine
      and its metabolites in urine and differentiation from an intake of structurally
      related medicaments using gas chromatography-mass spectrometry.
AB  - Studies are described on the toxicological analysis of the piperazine-derived
      designer drug 1-(4-methoxyphenyl)piperazine (MeOPP) in rat urine using gas
      chromatography-mass spectrometry (GC-MS). The authors' systematic toxicological
      analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid
      liquid extraction and microwave-assisted acetylation allowed the detection of
      MeOPP and its metabolites 1-(4-hydroxy phenyl)piperazine and 4-hydroxyaniline in
      rat urine after administration of a single dose corresponding to doses commonly
      taken by drug users. Therefore, this procedure should also be suitable for
      detection of a MeOPP intake in human urine. However, the metabolites of MeOPP are
      not unique and can be produced from other drugs. Therefore, differentiation of
      use of this designer drug from use of the medicaments dropropizine, oxypertine or
      others, which are metabolized to the MeOPP isomer 1-(2-methoxyphenyl)piperazine,
      is discussed.

PMID- 14643515
TI  - Fast liquid chromatography-mass spectrometry glutathione measurement in whole
      blood: micromolar GSSG is a sample preparation artifact.
AB  - We describe a new, fast (6 min) and reliable method to measure reduced or
      oxidized glutathione (GSH) or (GSSG) in whole blood. The method is based on a
      LC/MS measurement in positive electrospray ionization mode after a
      chromatographic separation on a specific column which does not need any counter
      ion in the mobile phase, improving the sensitivity of detection. A 50 microl
      sample of whole blood is sufficient for analysis. We demonstrate that the lack of
      an alkylating agent during the sample preparation brings out an underestimation
      of GSH and an artefactual production of GSSG, corresponding to 2-3% of GSH. The
      simultaneous use of N-ethyl-maleimide and a strong deproteinising acid prevents
      these two drawbacks. This efficient and new method of preparation and analysis
      lets us show that, unexpectedly, GSH is stable in whole blood for some hours and
      that deproteinised samples can be stored without GSH loss for at least three
      weeks at -20 or -80 degrees C. The reference interval, measured on 22 volunteers,
      on blood samples collected either with heparin or with EDTA, is 1310 +/- 118
      microM for GSH and 0.62 microM for GSSG. The within-run precision of this method,
      with gamma glutamyl-glutamic acid as an internal standard, evaluated in three
      successive series (n = 30), lies between 2.1 and 4.8% for a GSH level at 580 or
      1150 microM. The one step sample preparation we propose seems well suited for GSH
      routine measurements in hospital laboratories and avoids any underestimation of
      GSH, a now well accepted biomarker of oxidative stress.

PMID- 14643516
TI  - Testing for kavain in human hair using gas chromatography-tandem mass
      spectrometry.
AB  - A sensitive, specific and reproducible method for the quantitative determination
      of kavain in human hair has been developed. The sample preparation involved a
      decontamination step of the hair with methylene chloride. The hair sample (about
      50 mg) was incubated in 1 ml of methanol for 1 h, in an ultrasonic bath, in
      presence of 20 ng of methaqualone-d7 used as internal standard. The methanolic
      solution was evaporated to dryness, and the residue reconstituted by adding 30
      microl of methanol. A 2 microl aliquot of the extract was injected onto the
      column (Optima5-MS capillary column, 5% phenyl-95% methylsiloxane, 30 m x 0.25 mm
      i.d. x 0.25 mm film thickness) of a Hewlett-Packard (Palo Alto, CA) gas
      chromatograph (5890). Kavain was detected by its parent ion at m/z 230 and
      daughter ions at m/z 111 and 202 through a Finnigan TSQ 700 MS/MS system. The
      assay was capable of detecting 30 pg/mg of kavain (limit of detection (LOD)).
      Linearity was observed for kavain concentrations ranging from 100 to 2000 pg/mg
      with a correlation coefficient of 0.998. Intra-day precision at 400 pg/mg was
      13.7%. The analysis of a segment of hair, obtained from an occasional consumer,
      revealed the presence of kavain at the concentration of 418 pg/mg. A higher
      concentration (1708 pg/mg) was detected in the corresponding pubic hair.

PMID- 14643517
TI  - Liquid chromatographic method for the determination of plasma itraconazole and
      its hydroxy metabolite in pharmacokinetic/bioavailability studies.
AB  - A sensitive and selective high-performance liquid chromatographic method was
      developed for the determination of itraconazole and its active metabolite,
      hydroxyitraconazole, in human plasma. Prior to analysis, both compounds together
      with the internal standard were extracted from alkalinized plasma samples using a
      3:2 (v/v) mixture of 2,2,4-trimethylpentane and dichloromethane. The mobile phase
      comprised 0.02 M potassium dihydrogen phosphate-acetonitrile (1:1, v/v) adjusted
      to pH 3.0. Analysis was run at flow-rate of 0.9 ml/min with excitation and
      emission wavelengths set at 260 and 365 nm, respectively. Itraconazole was found
      to adsorb on glass or plastic tubes, but could be circumvented by prior treating
      the tubes using 10% dichlorodimethylsilane in toluene. Moreover, rinsing the
      injector port with acetonitrile helped to overcome any carry-over effect. This
      problem was not encountered with hydroxyitraconazole. The method was sensitive
      with limit of quantification of 3 ng/ml for itraconazole and 6 ng/ml for
      hydroxyitraconazole. The calibration curve was linear over a concentration range
      of 2.8-720 ng/ml for itraconazole and 5.6-720 ng/ml for the hydroxy metabolite.
      Mean recovery value of the extraction procedure for both compounds was about 85%,
      while the within-day and between-day coefficient of variation and percent error
      values of the assay method were all less than 15%. Hence, the method is suitable
      for use in pharmacokinetic and bioavailability studies of itraconazole.

PMID- 14643518
TI  - Determination of cocaine, benzoylecgonine and cocaethylene in human hair by solid
      phase microextraction and gas chromatography-mass spectrometry.
AB  - The present work describes a highly precise and sensitive method developed to
      detect cocaine (COC), benzoylecgonine (BE, its main metabolite) and cocaethylene
      (CE, transesterification product of the coingestion of COC with ethanol) in human
      head hair samples. The method was based on an alkylchloroformate derivatization
      of benzoylecgonine and the extraction of the analytes by solid-phase
      microextraction (SPME). Gas chromatography-mass spectrometry (GC-MS) was used to
      identify and quantify the analytes in selected ion monitoring mode (SIM). The
      limits of quantification and detection (LOQ and LOD) were: 0.1 ng/mg for COC and
      CE, and 0.5 ng/mg for BE. Good inter- and intra-assay precision was observed. The
      dynamic range of the assay was 0.1-50 ng/mg. The method is not time consuming and
      was shown to be easy to perform.

PMID- 14643519
TI  - Keratinocytes can differentiate into eccrine sweat ducts in vitro: involvement of
      epidermal growth factor and fetal bovine serum.
AB  - BACKGROUND: in addition to formation of an epidermal sheet and dermal
      substitution, reconstruction of skin that possesses functionality is an important
      goal for dermatologists. OBJECTIVE: we attempted to regenerate eccrine sweat
      glands in vitro. METHODS: we constructed skin equivalent models with various
      combination of normal human keratinocytes and fibroblasts and also examined the
      effect of various growth factors. RESULTS: we found that keratinocytes invaded
      the collagen gels and formed eccrine duct-like structures, only when (i) the
      culture media contained at least 15 ng/ml of epidermal growth factor (EGF) and
      fetal bovine serum (FBS), (ii) the keratinocytes were derived from young donors,
      and (iii) fibroblasts were present in the gel. Interestingly, when cultured under
      the same conditions eccrine gland duct cells were unable to invade the gel.
      Immunohistochemical analyses revealed induction of carcinoembryonic antigen by
      EGF at the inner part of the eccrine duct-like structures. Proliferating cell
      nuclear antigen was expressed mainly in basal layers of the epithelia but was not
      observed in the deeply invaded part. Cytokeratin profiles of the reconstructed
      epithelia were consistent with those of the regenerating epidermis and partly
      with the eccrine sweat duct. CONCLUSIONS: although not perfect model, these
      results indicate that 'young' keratinocytes could differentiate into/toward
      eccrine sweat ducts in vitro in the presence of EGF and FBS in cooperation with
      dermal fibroblasts.

PMID- 14643520
TI  - Alterations of immune functions in barrier disrupted skin by UVB irradiation.
AB  - BACKGROUND: While immunologic events elicited by acute barrier disruption or UVB
      irradiation have been studied in detail, the biological sequel of multiple
      insults to the skin is not well understood. OBJECTIVE: Since the skin would
      receive a variety of simultaneous stimuli in daily life, we tested the effects of
      sequential treatments with barrier disruption and UVB exposure on skin immunity.
      METHODS: Earlobes of BALB/c mice received tape-stripping and subsequently low
      dose UVB exposure. Control mice were treated with either tape-stripping or UVB.
      The expression of surface markers and cytokine production in Langerhans cells and
      keratinocytes and the elicitation response of contact hypersensitivity were
      compared. RESULTS: By flow cytometry, tape-stripping augmented the expression of
      MHC class II, CD54, CD80, CD86 and CD40 on Langerhans cells, whereas UVB
      decreased the expression of some of these molecules. Combination of tape
      stripping and UVB induced largely intermediate levels between these two. Upon
      stimulation with L cells expressing CD40L, Langerhans cells from tape-stripped
      and UVB-irradiated earlobes strongly transcribed mRNA for interleukin-1beta
      compared to each treatment. In keratinocytes, tape-stripping or UVB slightly
      upregulated tumor necrosis factor-alpha and interleukin-1alpha production at both
      mRNA and protein levels, whereas these two treatments synergistically increased
      the production of these cytokines. The in vitro hapten-presenting ability of
      Langerhans cells to trinitrophenyl-immune lymph node T cells ranked first in tape
      stripping, second in tape-stripping plus UVB and third in UVB, and so did the
      intensity of elicitation responses in contact hypersensitivity to a hapten,
      picryl chloride. CONCLUSION: It is suggested that barrier disruption and UVB
      antagonize with each other in contact hypersensitivity as a reflection of their
      effects on Langerhans cell antigen-presenting function, but they synergize in
      cytokine production by both Langerhans cells and keratinocytes.

PMID- 14643521
TI  - Analysis of gene mutations in three cases of dermatofibrosarcoma protuberans
      (DFSP): ordinary DFSP, DFSP with fibrosarcomatous lesion (DFSP-FS) and lung
      metastasis of DFSP-FS.
AB  - BACKGROUND: Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet
      derived growth factor B-chain (PDGFB) gene has been pointed out in
      dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have
      been shown to be involved in the fusion with exon 2 of the PDGFB gene. OBJECTIVE:
      We studied the breakpoints of the COL1A1 gene using the tumor specimens from
      three patients with DFSP. METHODS: Reverse transcriptase-polymerase chain
      reaction (PCR) was performed using cultured DFSP tumor cells or frozen tissue.
      Nucleotide sequence analysis was carried out using the PCR products to identify
      the breakpoints. RESULTS: Cases 1, 2 and 3 were diagnosed as ordinary DFSP, DFSP
      with fibrosarcomatous lesion (DFSP-FS) and lung metastasis of DFSP-FS,
      respectively. The COL1A1-PDGFB fusion transcripts were detected from the tumor
      specimens. Sequence analysis revealed that the ends of exons 42, 29 and 38 in the
      COL1A1 gene were fused with the start of exon 2 in the PDGFB gene in case 1, 2
      and 3, respectively. CONCLUSION: This study identified a novel COL1A1 breakpoint,
      namely, exon 42 of the COL1A1 gene. Detection of the aberrant fusion transcript
      seems to be useful at differential diagnosis both in primary and metastatic
      lesions.

PMID- 14643522
TI  - Detection of tyrosinase and tyrosinase-related protein 1 sequences from
      peripheral blood of melanoma patients using reverse transcription-polymerase
      chain reaction.
AB  - BACKGROUND: malignant melanoma has one of the highest rates of metastasis. Unlike
      other solid cancers, no sensitive tumor markers or laboratory tests that can
      provide information of the risk of metastasis and predict the prognosis have yet
      been established. OBJECTIVE: the study was done to establish a RT-PCR sensitive
      and specific enough to detect melanocyte-specific transcripts from peripheral
      blood cells. METHODS: peripheral white blood cells were collected from 30 healthy
      donors and 43 melanoma patients. Melanocyte-specific tyrosinase (TYR) and
      tyrosinase-related protein 1 (TYRP1) were selected as targets of RT-PCR. The
      sensitivity of detection using SK-mel-23 melanoma cells and rates of false
      positiveness using non-melanoma blood were compared between single-step PCR and
      nested PCR. Analysis of melanoma blood samples was carried out by the single-step
      PCR. RESULTS: the nested RT-PCR amplified the TYR and TYRP1 sequences from 14 and
      2 of the 30 healthy bloods, respectively. However, the single-step RT-PCR did not
      amplify TYR or TYRP1 sequences from any of the healthy controls. Our single-step
      RT-PCR detected 1.7 and 0.8 SK-mel-23 melanoma cells per ml blood for TYR and
      TYRP1, respectively. Overall, TYR mRNA was detected in 15 of the 43 melanoma
      patients (34.9%), and TYRP1 mRNA in 16 of the 43 (37.2%). The specificities of
      detection of TYR and TYRP1 were 83.3 and 88.9%, respectively. CONCLUSION: our
      single-step RT-PCR for TYR and TYRP1 mRNAs is more specific than the previous
      nested RT-PCR for TYR and applicable to detect circulating melanoma cells.

PMID- 14643523
TI  - An anti TGF-beta antibody increased the expression of transforming growth factor
      beta, matrix metalloproteinase-1, and elastin, and its effects were antagonized
      by ultraviolet radiation in epidermal keratinocytes.

PMID- 14643524
TI  - Compound heterozygosity for premature termination codon and glycine substitution
      mutations in the COL7A1 gene in Korean siblings with a moderately severe
      phenotype of recessive dystrophic epidermolysis bullosa.

PMID- 14643525
TI  - Differential diagnosis between mycosis fungoides and chronic dermatitis by
      fractal analysis.

PMID- 14643526
TI  - Serum levels of interleukin-18 in subjects affected by occupational allergic
      contact dermatitis.

PMID- 14643527
TI  - Imbalance of peripheral leukocyte and lymphocyte subpopulations in segmental
      vitiligo in Taiwanese.

PMID- 14643528
TI  - Quercetin inhibits fibronectin production by keloid-derived fibroblasts.
      Implication for the treatment of excessive scars.

PMID- 14643529
TI  - Pro-inflammatory cytokine interleukin-1alpha is downregulated during anagen phase
      of hair cycle in vivo.

PMID- 14643530
TI  - [Body mass index charts: what is the matter?].

PMID- 14643531
TI  - [Effectiveness of chest physiotherapy in ventilated children with acute
      bronchiolitis].
AB  - OBJECTIVES: Despite the lack of clinical studies, chest physiotherapy (CP) is
      widely used in children with acute bronchiolitis. The main goal of this study was
      to evaluate its short-term efficacy in children under mechanical ventilation for
      acute bronchiolitis. METHODS: Twenty children were studied. All were under
      mechanical ventilation on a pressure-controlled mode. Oxygen saturation,
      transcutaneous PCO2 and tidal volume were measured before any intervention, after
      endotracheal suction, after CP and endotracheal suction and 1 h later. RESULTS:
      Thirty-eight analyses were performed. Baseline tidal volume, oxygen saturation
      and transcutaneous PCO2 were not modified after endotracheal suction. Immediately
      and 1 h after CP, SpO2 (98% vs. 94.5%), and tidal volume (66 vs. 55 ml)
      significantly increased. CONCLUSION: The increase of O2 saturation and tidal
      volume may be linked to the improvement of bronchial sputum clearance. Further
      studies are needed to estimate the long-term efficacy of CP in acute
      bronchiolitis.

PMID- 14643532
TI  - [The safety and immunogenicity of an heptavalent pneumococcal polysaccharide
      conjugate vaccine (Prevenar) administered in association with a whole-cell
      pertussis-based pediatric combination vaccine (DTP-IPV/PRP-T) to French infants
      with a two-, three-, and four-month schedule].
AB  - Invasive pneumococcal disease is presently a leading cause of mortality due to
      bacterial infectious diseases in French children less than 2 years of age, and
      only the pneumococcal conjugate vaccines induce a protective immune response for
      those within this vulnerable age group. MATERIAL AND METHODS: The safety and
      immunogenicity of a heptavalent pneumococcal polysaccharide conjugate vaccine
      (PREVENAR was tested in French infants immunized with the 2, 3 and 4 month French
      schedule as part of an open, randomized, comparative clinical study, in
      association with a whole-cell pertussis-based pediatric combination vaccine.
      RESULTS: In the PREVENAR plus DTP-IPV/Hib association group, 90.6-100% of
      children achieved a post-dose three threshold IgG concentration of >0.15
      microg/ml against each of the seven pneumococcal serotypes. Regarding
      immunogenicity, no interference with the antibody response to the various
      antigenic components of the DTP-IPV/Hib vaccine was observed. Local reactions
      were significantly less frequent at the PREVENAR injection site than at the DTP
      IPV/Hib injection site; there was no increase in systemic adverse events in the
      vaccine association group compared to the DTP-IPV/Hib alone group, further
      exception of fever >38 degrees C which was more frequently reported in the
      PREVENAR + PENTACOQ group following the second dose of vaccines (56% vs. 35%); no
      serious adverse event could be considered to be related to the PREVENAR
      immunization in this study. CONCLUSION: The heptavalent pneumococcal conjugate
      vaccine is immunogenic when administered at 2, 3 and 4 months. PREVENAR can be
      administered simultaneously with the DTP-IPV/Hib combination vaccine.

PMID- 14643534
TI  - [Pertinence of parental screening for delays of language in children aged four to
      six years].
AB  - This study investigates the relevance of the information provided by parents when
      screening for language delays in pre-school children. METHOD: Parents of 670
      pupils of medium section of nursery school (4-5 years) and of 799 pupils of the
      high section of nursery school (5-6 years) answered questions about their child's
      language and behaviour. Some of these same children passed currently available
      ERTL4 and BREV tasks (in medium section) and BSEDS tasks (in high section). Items
      concerning language delay were selected from the parents' questionnaire by the
      principal component analysis method, and correlation between parental answers to
      these items and the task results were examined. RESULTS: Parents' opinion was
      strongly and specifically correlated with tasks assessing the correct/incorrect
      aspects of speech and expressive language and less strongly with tasks assessing
      vocabulary or comprehension. CONCLUSION: Parents' opinion is useful when
      screening for delays of speech and expressive language in pre-school children.

PMID- 14643533
TI  - [Community acquired pneumonia and influenza in children].
AB  - Children without chronic or serious medical conditions are at increased risk for
      hospitalization during influenza seasons, mainly with respiratory tract
      infections. But influenza virus infections frequently remain undiagnosed, even in
      hospitalized patients. We prospectively studied the rate of concomitant and
      preceding influenza infections in children hospitalized with a community acquired
      pneumonia (CAP). POPULATION AND METHODS: All 1-15-year-old children with CAP
      requiring hospitalization between 1st April 2000 and 2002 had nasopharyngeal
      aspirate for viruses, immunofluorescence and serologies for respiratory
      pathogens. The peak of influenza IgG measured by complement fixation (CF) is
      transient, and a titer of 1/64 or more indicates an acute influenza infection in
      the preceding weeks. Children with chronic disease were excluded and a control
      group of patients from outpatient clinic was measured. RESULTS: Among 33
      previously healthy children (age 4.9 years, range 1.2-14 years), 8 had a
      pneumococcal pneumonia, 10 a pneumonia caused by Mycoplasma pneumoniae (MP), 1 by
      Chlamydia pneumonia, and 8 of unknown origin. In six patients immunofluorescence
      was positive: Respiratory Syncitial Virus, 2, Adenovirus, 1 and Influenza A, 3
      (including a patient with concomitant MP infection). Thirteen of the 33 children
      (39.4%) had evidence of a recent influenza A infection with CF ab > or = 1/64:
      with pneumococcal pneumonia, 5/10 with MP pneumonia, 3/8 with unknown origin
      pneumonia, 9/13 of these previous influenza infections being clinically
      inapparent. Only 1/30 children of control group (3.3%) had CF ab > or = 1/64.
      CONCLUSION: In this study, influenza infection is the direct cause of CAP of
      children in 12% of cases. In other children with CAP, 39.4% of patients had an
      influenza infection in the preceding weeks which leads to secondary infection
      caused by Streptococcus pneumoniae or by MP or other pathogens.

PMID- 14643535
TI  - [Necrobacillosis and Lemierre's syndrome: case report].
AB  - Necrobacillosis (Fusobacterium necrophorum septicaemia) and Lemierre's syndrome
      (human necrobacillosis with cephalic origin) are not widely known by clinicians.
      CASE REPORT: We report the case of a 5-year-old girl, presenting with a
      Lemierre's syndrome consecutive to otitis media. Outcome was favourable under
      metronidazole and amoxicilline therapy for 6 weeks. CONCLUSION: Necrobacillosis
      remains a severe disease including peripheral abscesses (mainly in the lungs and
      the liver), often associated with thrombosis of the internal jugular vein in case
      of Lemierre's syndrome. Prolonged metronidazole and amoxicilline antibiotherapy
      allows nowadays a healthy outcome.

PMID- 14643536
TI  - [Bilateral jugular thrombosis in Lemierre syndrome].
AB  - An adolescent presented with a rhinosinusitis complicated with bilateral jugular
      veins and left superior ophthalmic vein thrombosis and respiratory distress with
      pulmonary hypertension. Blood culture was positive for Haemophilus influenzae and
      sinus puncture for Streptococcus constellatus. Evolution was under control after
      1 week of appropriate antibiotherapy, antithrombotic and anti-inflammatory
      treatment. He had no neurologic, respiratory or ophthalmologic sequelae 6 months
      later. Despite lack of pharyngitis or isolation of anaerobic species on blood
      cultures, the picture was considered compatible with Lemierre syndrome. The risk
      for such a complication should be considered in cases of severe
      otorhinolaryngologic infection in young adults.

PMID- 14643537
TI  - [Dumbbell nephroblastoma: an uncommon cause of spinal cord compression].
AB  - Rarely children with Wilms' tumor develop spinal cord dysfunction by metastatic
      spread into the epidural space or the cord parenchyma. In the case reported here,
      the mechanism of spinal compression was different. CASE REPORT: The authors
      report the clinical course of a 2-month-old boy with retroperitoneal extrarenal
      Wilms' tumor below the left kidney, characterized with a spinal cord compression
      developed through the intervertebral foramina. CONCLUSION: Abdominal tumor,
      usually corresponding to neuroblastoma, may be a nephroblastoma.

PMID- 14643538
TI  - [Acute neonatal appendicitis in an inguinal hernia].
AB  - Acute neonatal appendicitis is a rare surgical emergency. Prognosis depends on
      early diagnosis and management. CASE REPORT: A three and a half-month-old
      premature infant needed an urgent laparotomy because of an occlusive syndrome and
      sepsis with an inflammatory skin reaction. The per-operative diagnosis was
      suppurative acute appendicitis with local peritonitis, the appendix being
      strangulated into the inguinal hernia. DISCUSSION: Neonatal appendicitis
      represents 0.1% of all infantile appendicitis. Fifty percent of such cases occur
      in premature infants. Two clinical presentations exist, whose diagnosis is often
      made during surgery. The abdominal presentation (2/3 of the cases) can mimic
      necrotizing enterocolitis; the diagnosis is often late and evolution leads to
      diffuse peritonitis in the majority of the cases, while the mortality rate is
      higher than 50%. The intra-hernial presentation (1/3 of the cases), instead, is
      usually diagnosed and managed early due to the inguino-scrotal induration, while
      mortality rate is near zero. CONCLUSION: The high frequency of inguinal hernia in
      premature infants should not mask the risk for intra-hernial appendicitis.
      Inguino-scrotal inflammation should evoke the diagnosis. Prognosis depends on
      early and urgent surgical management.

PMID- 14643539
TI  - [Inhaled treatments delivery in children].
AB  - The most efficient method to deliver drugs to the lungs in children is the
      inhaled way. Its success depends on the characteristics of the aerosol, on those
      of the patient, and mainly on the inhalatory system. Before the age of 8 years,
      the most efficient system is the pressurised metered dose inhaler used together
      with a spacer device. Above this age, the use either of the pressurised metered
      dose inhaler, with a spacer device or a breath-actuated inhaler, or of a dry
      powder inhaler is discussed. Nebulisation is rarely indicated, except in cystic
      fibrosis. Demonstration with repeated medical instructions allows adequate
      inhalation technique. Inhaled treatments are efficient when used in diseases
      requiring this type of treatment, when several inhalers with different inhalatory
      techniques are not prescribed together, and when delivery is once or twice daily.
      At last, inhaled way is a new approach for different drugs with an extra
      respiratory activity.

PMID- 14643551
TI  - [Current aspects of tuberculosis in Dakar pediatric area].

PMID- 14643552
TI  - [Prevention strategies of childhood obesity].
AB  - Considering the high prevalence and the increasing trends, obesity is now
      considered as a public health problem in numerous countries. The main aim of the
      National Program of Nutrition and Health is to stop the increasing prevalence of
      childhood obesity. In this frame work, a group of experts has established a new
      presentation of the corpulence curves, adapted for clinical practice, to define
      normal weight and obesity. Weight status is now currently assessed on the basis
      of weight and height measurements, after computing the Quetelet index or body
      mass index (BMI) corresponding to weight (m) divided by square of height
      (weight/height2). As body proportion varies during growth, age must be taken into
      account. Various curves were published. In 1982, based on the French sample of
      the international growth study, BMI curves were published. They were revised in
      1991. The third and 97th centiles define the normal weight range. Overweight is
      defined by BMI values greater than the 97th centile. In the year 2000, a new
      international definition was established. Two centiles were constructed to define
      overweight and obesity. The new BMI charts adapted for clinical practice,
      proposed by the French National program of nutrition and health, include the
      French reference curves plus the centile defining obesity in the international
      definition. Thus, in the new French charts, the area above the 97th centile is
      split in two levels (degree 1 obesity and degree 2 obesity). Drawing the BMI
      curve for each child, like drawing weight and height curves, is a simple act
      which can be done routinely. The age at adiposity rebound (an indicator
      predicting the risk of adult obesity) can be read from the curve. It allows to
      identify an early phase of obesity development, even at the time when overweight
      is not yet clinically visible. When obesity appears clearly, the identification
      is easy. The use of BMI curves is particularly useful in two situations: (1) in
      very young overweight children, the curves allow to identify children who have a
      real risk of developing obesity. (2) By the age of 6 years, when due to normal
      physiological variations, clinical assessment can be misleading. The BMI curves
      allow to identify children at risk. When a child is identified as having a real
      risk of obesity, simple preventive measures, adapted for each subject, could
      avoid a development toward massive obesity, which may become difficult to reduce
      if managed too late.

PMID- 14643553
TI  - [Guidelines for positive tuberculin test].
AB  - Tuberculin skin test is still the only proven method for identifying infection
      wtih M. tuberculosis in persons who do not have active disease. Targeted
      tuberculin testing for latent tuberculosis infection is a strategic component of
      tuberculosis control in low prevalence countries. This report describes
      indication, technical method, interpretation of this test and guidelines when the
      tuberculin test is positive.

PMID- 14643555
TI  - [Prurigo].

PMID- 14643554
TI  - [Chickenpox during pregnancy].
AB  - Varicella during pregnancy is a rare occurrence because of a high rate of
      spontaneous immunisation in the population. When a pregnant woman presents a
      typical rash, maternal complications, mainly respiratory distress, can occur and
      be life threatening. Fetal complications include two types of consequences.
      Before 24 weeks of gestation, transplacental transmission is estimated around 6%,
      with about one third of infected fetuses presenting clinical manifestations.
      Congenital varicella syndrome includes growth retardation, neurological effects
      as microcephaly, limbs malposition, lung or bowel hyperechogenicity. But most
      infected fetuses will not show any anomaly. A very few might develop shingles in
      the first year of life. Peripartum contamination brings a much higher risk of
      transmission (around 25%). Neonatal varicella infection can be life threatening
      for the new born baby, especially if premature. A specific treatment should be
      started as soon as the contamination is discovered. Zoster during pregnancy does
      not lead to a risk of fetal infection.

PMID- 14643556
TI  - [Consensus conference. Management of chronic urticaria].

PMID- 14643559
TI  - Antidepressant prescribing and suicide rate in Northern Ireland.
AB  - PURPOSE: Although antidepressants are the most commonly used treatment for
      depressive illness, there is uncertainty if their use is associated with a
      reduction in suicide rate. Antidepressant prescribing in Northern Ireland has
      increased over fivefold in the decade 1989-1999. The authors sought to explore
      whether this increase was associated with a reduction in suicide rate taking into
      account social and political factors thought also to have an influence on
      suicide. MATERIALS AND METHODS: Factors that have been suggested to influence
      suicide were entered into a linear regression with frequency of suicide and
      undetermined deaths (referred to as suicide rate) as the dependent variable. The
      above factors were antidepressant prescribing, unemployment rate, household
      alcohol expenditure and persons charged with terrorist offences. The rise in
      younger suicides, in recent decades, suggests this analysis should be carried out
      separately for younger (less than 30 years) and older (30 years and above)
      suicides separately. The predictors in the two models are based on aggregate data
      for the total group. RESULT: In the younger group there was no association
      between antidepressant prescribing and suicide. For the older group increased
      antidepressant prescribing was associated with a reduction in suicide rate over
      the 10 years of the study. CONCLUSION: Increasing antidepressant prescribing
      appears to be an effective strategy for reducing suicide. This has been
      demonstrated in older individuals.

PMID- 14643560
TI  - Attitudes towards suicide and suicidal patients among medical students.
AB  - Medical students' attitudes towards suicide and suicidal patients were studied.
      The aim was also to determine whether attitudes differ between students in the
      beginning and end of studies. A questionnaire including own attitudes on death
      and suicide and psychosocial circumstances was filled in by 63% of first and
      final year students (306 of 485). The calculation included a factor analysis on
      items describing the attitudes to suicidal patients. Attitudes towards patients
      became influenced by the knowledge of mental disorders and by biological aspects
      of behaviour during the education. Final year students more often consider
      suicide to be an expression of psychiatric disease and thought that people trying
      to commit suicide were not responsible for their own actions. Thirty-four percent
      and 44% (ns) in the first and last years, respectively, reported suicidal ideas
      some time in their lives. Students with such a history of suicide thoughts were
      less optimistic about the possibility to help. Ongoing depressive/anxious
      symptoms were prevalent in 36/305 (12%) of students, but did not seem to affect
      their attitudes to patients. Female students had sought psychological/psychiatric
      help more often than males (26% and 10%, P < 0.01).

PMID- 14643561
TI  - Exploring the link between character, personality disorder, and
      neuropsychological function.
AB  - Personality deviations and deficits in cognitive executive function are common
      among forensic populations. The present study on incarcerated offenders explored
      whether there are links between the two domains. Personality was assessed using
      the Temperament and Character Inventory (TCI). Neuropsychological performance,
      including visual working memory, attentional set-shifting and planning, were
      tested with the Cambridge Neuropsychological Test Automated Battery (CANTAB).
      Subjects with personality disorders scored high on harm avoidance, and low on
      self-directedness and cooperativeness. Personality disordered offenders did not
      differ from the comparison groups (offenders without personality disorder, and
      non-criminal controls) with regard to CANTAB measures of visual working memory
      (delayed matching to sample, spatial working memory) and planning (Stockings of
      Cambridge), but they made a larger number of errors on the attentional set
      shifting task. Dimensional analysis of the personality and neuropsychological
      variables revealed significant associations between self-directedness and
      cooperativeness on the one hand, and attentional set-shifting on the other.
      Intellectually disabled, non-criminal individuals (marginal mental retardation)
      who performed poorly on attentional set-shifting also scored low on self
      directedness and cooperativeness. The results indicate that poor development of
      certain personality traits may be associated with deficits in neuropsychological
      functioning.

PMID- 14643562
TI  - Frequency and impact of patient suicide on psychiatric trainees.
AB  - The objective of the present study was to conduct a systematic inquiry into the
      frequency and impact of patients' suicide on psychiatric trainees, and the
      availability and usefulness of training courses. Data were collected from 114
      psychiatric trainees of the Dutch-speaking part of Belgium, representing a 70%
      response rate. A self-report questionnaire developed in the UK was adapted to the
      Flemish situation. A Dutch version of the Impact of Event Scale (IES) inquiring
      about post-traumatic stress symptoms was also used. The frequency of suicide
      experience was considerably higher in the present study than in similar studies
      in the USA and the UK. Thirty percent of first year trainees had been confronted
      with patient suicide. Personal and professional impact of patient suicide, as
      well as post-traumatic stress scores were considerably lower in Flemish
      psychiatric trainees. They considered informal support to be of more value than
      formal support to come to terms with the event. Finally, postgraduate training in
      post-suicide management was found to be largely insufficient. The results of the
      present study show that psychiatric trainees in the Dutch-speaking part of
      Belgium are at a high risk of experiencing patient suicide, whereas the impact of
      this experience appears to be relatively low. Only a small minority of trainees
      has received adequate training on procedures to follow after patient suicide.

PMID- 14643563
TI  - The dexamethasone suppression test and DSM-III-R diagnoses in suicide attempters.
AB  - Previous research on hypothalamic-pituitary adrenal (HPA) axis-activity in
      suicide attempter research has shown conflicting outcomes. The design of the
      present study was to test the influence of personality disorders and concominant
      axis I diagnoses on the dexamethasone suppression diagnostic test by use of
      multiple regression analyses. The sample consisted of 184 patients with a recent
      suicide attempt and 42 healthy controls. As expected, the lowest pre- and
      postdexamethasone cortisol levels were found in patients with personality
      disorders axis II, cluster B as compared to the other patients. The results
      remained significant when analysed for covariance with DSM-III-R axis I
      diagnoses, age or sex. Whether these low cortisol levels are due to previous
      experience of extreme stressful events or long-lasting burden, or whether they
      may be a consequence of biogenetic or psychological predisposal of interest,
      remains to be elucidated. Axis I comorbidity needs to be further examined.

PMID- 14643564
TI  - The A1 allele of the DRD2 gene (TaqI A polymorphisms) is associated with
      antisocial personality in a sample of alcohol-dependent patients.
AB  - BACKGROUND: Presence of A1 allele of the DRD2 gene has been associated with a
      predisposition for alcoholism although there are limited data about its
      phenotypic expression in alcoholism. OBJECTIVES: To determine the importance of
      the A1 allele in clinical variables of alcohol dependence. METHODOLOGY: A sample
      of 103 alcohol-dependent males was studied. All patients were recruited
      consecutively from the general hospital and community settings. The diagnostics
      were made with the structured clinical interview for DSM-III-R (SCID); and the
      International Personality Disorder Examination (IPDE). Diagnosis of family
      alcoholism was made by direct interview or with the Research Diagnostic Criteria
      Family History (RDC-FH). The Addiction Severity Index (ASI) and the Severity of
      Alcohol Dependence Scale (SADS) were used to assess alcohol dependence severity.
      Genotyping was done by polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP) methods. RESULTS: Approximately 39% of the sample
      carried the A1 allele (A1+ group). This group had higher prevalences of
      antisocial personality disorder (60% vs. 15.9%); and alcoholism family history
      (72.5% vs. 52.4%). Also A1+ had early onset alcohol abuse and more drinking
      problems. The presence of A1+ was the main factor to explain the diagnosis of
      antisocial personality disorder, but the weight of this factor was not sufficient
      to explain the complications assessed by the ASI. CONCLUSIONS: Our results
      support the existence of an association between the A1 allele and factors
      resulting from dopaminergic deficiency, otherwise denominated reward deficiency
      syndrome.

PMID- 14643565
TI  - MINI International Neuropsychiatric Schedule: clinical utility and patient
      acceptance.
AB  - OBJECTIVE: Clinical diagnosis has been shown to be unreliable compared to
      structured diagnostic schedules. However, clinicians rarely use structured
      diagnostic schedules due to concerns about the feasibility in clinical practice
      and about patient acceptance. Mini International Neuropsychiatric Schedule is a
      short diagnostic instrument validated against SCID and CIDI but its feasibility
      and patient acceptance has not been studied. SUBJECTS AND METHODS: One hundred
      and eleven patients admitted to a partial program were administered Mini
      International Neuropsychiatric Schedule and the interview was timed. A short
      questionnaire was administered to assess patients' views about the interview. For
      a subgroup of patients, diagnoses by both open interviews and Mini International
      Neuropsychiatric Interview (MINI) were available. These were compared to look for
      agreement in primary diagnoses and co-morbid conditions. RESULTS: MINI took an
      average of 16.4 min to administer. Patients' views of MINI were positive. It was
      considered comprehensive enough to cover all patient symptoms and at the same
      time not unduly lengthy. Patients were not bothered by the interview format.
      There was disagreement between MINI primary diagnosis and open diagnosis in 42%
      cases. In 33% the disagreement was of substantial clinical significance. MINI
      diagnosed more co-morbid conditions (average 2.05 compared to 0.5 in open
      interview). CONCLUSIONS: MINI is a short diagnostic interview schedule that can
      be easily incorporated into routine clinical interviews. It has good acceptance
      by patients.

PMID- 14643566
TI  - Body dysmorphic disorder in a sample of cosmetic surgery applicants.
AB  - Body dysmorphic disorder (B.D.D.) consists of a preoccupation with an imagined or
      slight physical defect. This study is the first European report on prevalence and
      several clinical and functional characteristics of patients with B.D.D. in a
      cosmetic surgery setting. Comparisons with defect- and severity-matched subjects
      without B.D.D. were also performed.

PMID- 14643567
TI  - Combined use of platelet serotonergic markers and psychopathological scales as
      diagnostic screening of a psychotic versus a depressive disorder.
AB  - A single case of a patient suffering from a first psychotic episode and the
      differential diagnoses between affective and psychosis is performed throughout
      the combined use of peripheral serotonergic markers and clinical
      psychopathological scales during a 6-months follow-up. The results suggest the
      need of performing further studies combining biological and clinical markers of
      psychiatric disorders.

PMID- 14643568
TI  - Quetiapine in the elderly with parkinsonism and psychosis.
AB  - In the present open prospective study the effects of quetiapine were investigated
      in two elderly patients with parkinsonism and psychosis. Treatment induced a
      marked antipsychotic effect that coincided with an improvement of general motor
      functioning. These findings support the idea that quetiapine may be
      preferentially of use in the elderly with parkinson's disease and psychotic
      symptoms.

PMID- 14643569
TI  - Schedule for affective disorders and schizophrenia for school-age children
      present episode (K-SADS-P): a pilot inter-rater reliability study for Greek
      children and adolescents.

PMID- 14643570
TI  - Likelihood ratios in the diagnosis of renal artery stenosis by magnetic resonance
      angiography compared with renal angiography.
AB  - BACKGROUND: Renal angiography (RA) is considered to be the gold standard for the
      diagnosis of renal artery stenosis (RAS). However, it is invasive and potentially
      harmful; hence there is a need for an optimal noninvasive test. Magnetic
      resonance angiography (MRA) is currently accepted as the optimal noninvasive test
      by many. However, its major drawback is its inability to grade quantitatively the
      degree of stenosis. In this study, likelihood ratios (LR) were used to compare
      the diagnostic accuracy of MRA with that of RA. METHODS: To test the hypothesis
      that semiquantitatively graded MRA would correlate with RA, a retrospective
      analysis was performed to determine the LR of MRA to diagnose RAS compared with
      RA. It was believed that LR > or = 10.0 or < or =0.1 might generate conclusive
      changes from pretest to post-test probabilities. In this study a total of 94
      renal arteries from 48 patients were analyzed for RAS by MRA and RA. Stenoses
      were graded by MRA as mild (<50%), moderate (50% to 75%), or severe (>75%); and
      by RA as <75% or > or =75% stenosis. RESULTS: The LR was 0.13 (95% CI = 0.09 to
      0.19) for mild stenosis, 0.11 (95% CI = 0.08 to 0.15) for moderate stenosis, and
      2.2 (95% CI = 1.9 to 3.1) for severe stenosis by MRA. CONCLUSIONS: Nonsevere
      stenosis can be sufficiently diagnosed by MRA and may not warrant RA. However, it
      may be insufficiently precise to establish severe RAS based on LR results.
      Therefore, for severe RAS by MRA, the decision to obtain RA can be made with the
      help of post-test probability, which is determined using pretest probability and
      LR.

PMID- 14643571
TI  - Expression of endothelial angiotensin II receptor mRNA in pregnancy-induced
      hypertension.
AB  - OBJECTIVE: The normal suppression of vascular sensitivity to angiotensin II (Ang
      II) in pregnancy is lost in pregnancy-induced hypertension (PIH). To examine the
      mechanism, we investigated Ang II receptor subtype 1 (AT1R) and 2 (AT2R)
      expression in human umbilical vein endothelial cells (HUVEC) and vascular smooth
      muscle cells (VSMC). METHODS: The HUVEC and VSMC were incubated with serum from
      normal pregnant women and PIH patients for 0 to 12 h. The AT1R and AT2R mRNA were
      semiquantified as the ratio to glyceraldehyde-3-phosphate dehydrogenase mRNA,
      using multiplex reverse transcription-polymerase chain reaction. The AT1R
      expression was also evaluated by immunocytochemistry. RESULTS: Serum from PIH
      patients significantly increased AT1R mRNA of HUVEC (1.48 +/- 0.44) after a 12-h
      incubation compared with that from normal pregnant women (0.25 +/- 0.14). On the
      other hand, AT2R mRNA of HUVEC incubated with serum from PIH patients (0.14 +/-
      0.02) was significantly decreased compared with HUVEC incubated with serum from
      normal pregnant women (0.31 +/- 0.08). The AT1R mRNA of VSMC was significantly
      increased by serum from both PIH patients and normal pregnant women. The AT1R-to
      AT2R mRNA ratio increased by serum from PIH patients was significantly reduced by
      anti-tumor necrosis factor-alpha (TNF-alpha) antibody (20 microg/mL). Valsartan
      (an AT1R antagonist, at 1 to 10 nmol/L) significantly increased AT2R mRNA of
      HUVEC. Also, immunocytochemistry demonstrated that endothelial AT1R expression
      was strongly increased by PIH sera and reduced by anti-TNF-alpha antibody.
      CONCLUSIONS: Endothelial AT1R expression is increased and AT2R expression is
      decreased in PIH. The TNF-alpha is related to the pathogenesis of PIH by reduced
      AT2R mRNA through an increase of AT1R mRNA.

PMID- 14643572
TI  - The effect of rapid decreases of blood pressure by different mechanisms on
      coronary flow and flow reserve in normal coronary arteries.
AB  - BACKGROUND: Changes in mean blood pressure (MBP) alter coronary blood flow (CBF).
      We evaluated the acute effects of three hypotensive medications on CBF parameters
      in angiographically normal coronary arteries. METHODS: We performed CBF
      measurements using the Doppler wire at rest and during hyperemia produced by
      intracoronary adenosine (18 microg) as follows: 1) in the normal left circumflex
      coronary artery in 20 patients with coronary artery disease (measurements were
      performed without drugs, and after intravenous infusion of nitroprusside [0.5 to
      2 microg/kg/min] and nitroglycerin [10 to 90 microg/min]; drugs were titrated to
      decrease MBP 20% to 25% below the control values, and heart rate was held
      constant using right atrial pacing); and 2) in the normal left anterior
      descending coronary artery in 19 patients without coronary artery disease
      (measurements were performed before and after intravenous clonidine infusion [150
      microg in 5 min]; time-averaged peak velocity [APV], CBF, and coronary flow
      reserve [CFR] were measured). RESULTS: Similar decreases in MBP were obtained in
      the two patient groups. Lumen diameter at the site of Doppler measurements
      increased after all medications (P <.005), whereas CBF did not change
      significantly. The CFR decreased after nitroprusside (1.79 +/- 0.48 v 2.54 +/-
      0.45, P=.000), did not change significantly after nitroglycerin (2.74 +/- 0.43 v
      2.54 +/- 0.45, P =.097), and increased after clonidine (3.12 +/- 0.70 v 2.76 +/-
      0.75, P =.006). CONCLUSIONS: In normal coronary arteries the infusion of three
      hypotensive medications to produce the same decreases in MBP is associated with
      different effects on CFR (increase with clonidine, decrease with nitroprusside,
      and no change with nitroglycerin).

PMID- 14643573
TI  - Impact of renin-angiotensin-aldosterone system gene variants on the severity of
      hypertension in patients with newly diagnosed hypertension.
AB  - BACKGROUND: The severity of hypertension has prognostic significance. Previous
      studies have assessed the relationship between renin-angiotensin-aldosterone
      system (RAAS) genotype and the severity of hypertension in either treated
      patients or those who have only recently discontinued treatment. METHODS: We
      assessed the impact of RAAS genotype on ambulatory and office blood pressure (BP)
      in 231 newly diagnosed hypertensive patients of African ancestry who had never
      received therapy. Subjects were genotyped for variants of the angiotensin
      converting enzyme (insertion/deletion), angiotensinogen (M235T, -20A-->C), and
      aldosterone synthase (CYP11B2)(-344C-->T) genes. RESULTS: The CYP11B2 gene
      polymorphism was associated with systolic BP (SBP). In comparison to subjects
      with at least one copy of the -344C allele (n = 75), patients who were homozygous
      for the -344T allele (n = 156) had both higher ambulatory SBP (150 +/- 1 v 144 +/
      1 mm Hg, P =.002 before and P =.01 after adjusting for multiple genotyping) and
      office SBP (163 +/- 2 v 156 +/- 2 mm Hg, P =.01 before and P =.05 after adjusting
      for multiple genotyping). Neither the angiotensin-converting enzyme
      insertion/deletion nor the angiotensinogen gene polymorphisms were associated
      with ambulatory or office SBP or diastolic BP (DBP). The CYP11B2 gene variant
      also did not affect DBP. CONCLUSION: A variant within the CYP11B2 locus has a
      clinically important impact on the severity of SBP changes in individuals with
      newly diagnosed hypertension who are of African ethnicity.

PMID- 14643574
TI  - Angiotensinogen Met235Thr polymorphism, angiotensin-converting enzyme inhibitor
      therapy, and the risk of nonfatal stroke or myocardial infarction in hypertensive
      patients.
AB  - The ThrThr genotype of the angiotensinogen (AGT) Met235Thr polymorphism has been
      associated with elevated AGT levels, hypertension, increased heart disease risk,
      and improved blood pressure (BP) response to angiotensin-converting enzyme (ACE)
      inhibitors. We hypothesized that risk of stroke or myocardial infarction (MI)
      associated with ACE inhibitor use varies by AGT genotype, with a larger
      protective effect of ACE inhibitors in individuals with the ThrThr genotype than
      individuals who are carriers of the Met allele. METHODS: We conducted a
      population-based case-control study. Participants were health maintenance
      organization members aged 30 to 79 years with treated hypertension. Those who
      survived incident stroke (n = 116) or MI (n = 208) during the study period were
      designated as cases. Control subjects (n = 717) were randomly sampled and
      frequency-matched to MI cases on age, sex, and calendar year. Health history,
      medication use, and AGT genotype were assessed. RESULTS: ThrThr genotype was
      present in 21% of stroke cases, 26% of MI cases, and 19% of control subjects.
      Compared with nonuse, ACE inhibitor use was associated with lower stroke risk
      among Thr homozygotes (odds ratio [OR] = 0.37, 95% CI = 0.14 to 0.99) than among
      Met carriers (OR = 1.4, 95% CI = 0.88 to 2.4; P for interaction =.02). Compared
      with nonuse, ACE inhibitor use was associated with similar MI risk among Thr
      homozygotes (OR = 0.90, 95% CI = 0.62 to 1.3) and among Met carriers (OR = 1.2,
      95% CI = 0.60 to 2.5; P for interaction = 0.5). CONCLUSIONS: In this hypertensive
      population, the association of ACE inhibitor use with risk of nonfatal stroke
      varied by genotype. The protective association between ACE inhibitor use and
      nonfatal stroke risk among individuals with ThrThr genotype was not observed for
      nonfatal MI.

PMID- 14643575
TI  - Alpha-adducin polymorphism, salt sensitivity, nitric oxide excretion, and
      cardiovascular risk factors in normotensive Hispanics.
AB  - BACKGROUND: Genetic and environmental factors determine the blood pressure (BP)
      response to changes in salt intake. Mutations in the alpha-adducin gene may be
      associated with hypertension and salt-sensitive hypertension. We investigated
      whether one alpha-adducin polymorphism, the Gly460Trp (G/T) variant, was
      associated with salt sensitivity, nitric oxide (NO) production; and
      cardiovascular risk factors in healthy adult normotensive Venezuelans. METHODS
      AND RESULTS: Subjects (n = 126) were screened for salt sensitivity. The alpha
      Adducin polymorphism was tested in salt-sensitive (SS) and salt-resistant (SR)
      subjects. The G/T and G/G (wild gene) groups had similar BP levels. The G/T
      subjects had higher LDL-cholesterol (P =.01) and postload glucose AUC (P =.03)
      than G/G individuals. Genotype frequencies were not associated with BP or salt
      sensitivity (G/G, 38.1% SS and 61.9% SR vs G/T, 40.7% SS and 59.3% SR). Shifting
      from high salt to low salt diet produced comparable reductions in systolic BP and
      diastolic BP in G/T and G/G groups. The G/G and G/T groups excreted similar
      amounts of sodium on high and low salt diets. The SR subjects carrying the wild
      or the mutated gene showed no changes in NO metabolite excretion at different
      levels of salt intake. In SS subjects, the level of NO metabolite excretion was
      highly dependent on salt intake. A combination of SS and 460Trp mutation enhanced
      the sodium-dependent modulation of NO production. CONCLUSIONS: In normotensive
      Venezuelans, the alpha-adducin G/T polymorphism was not associated with BP, salt
      sensitivity, or with sodium excretion during sodium loading or restriction. G/T
      was associated with increased LDL-cholesterol and postload glucose levels. In SS,
      G/T was associated with greater salt-dependent modulation of NO excretion.
      However, this larger increase in NO excretion was not associated with a larger
      decrease in BP.

PMID- 14643576
TI  - The limited value of plasma B-type natriuretic peptide for screening for left
      ventricular hypertrophy among hypertensive patients.
AB  - BACKGROUND: Several reports have suggested that plasma B-type natriuretic peptide
      (BNP) levels are elevated in hypertensive patients especially with left
      ventricular (LV) hypertrophy. However, few data have been available concerning
      the utility of plasma BNP measurement to identify LV hypertrophy in hypertensive
      patients in a general population screening context. METHODS: We measured plasma
      BNP concentrations in 1112 volunteers in a health screening program (mean age, 57
      years). All subjects underwent electrocardiography, chest X-ray, and
      echocardiography. Among the sample, 284 subjects were designated as hypertensive
      because they were on antihypertensive drugs or showed elevated systemic blood
      pressure. By echocardiography, 36 of the hypertensive patients showed significant
      LV hypertrophy. RESULTS: There were no significant differences in age and sex
      between the LV hypertrophy and non-LV hypertrophy groups. Plasma BNP levels in
      the LV hypertrophy group were significantly higher than in the non-LV hypertrophy
      group (19.4 +/- 18.9 v 28.2 +/- 28.2 pg/mL; P <.05). However, the ability of
      plasma BNP levels to discriminate between LV hypertrophy and non-LV hypertrophy
      patients was not sufficient as the area under the receiver operating
      characteristic curve was 0.588 (95% CI: 0.528-0.646) with sensitivity of 50.0%
      and specificity of 69.0%. Positive and negative predictive values for detecting
      LV hypertrophy among hypertensive patients were 18.9% and 90.5%, respectively.
      This ability did not improve significantly when the screening was limited to
      patients with untreated LV hypertrophy or concentric LV hypertrophy. CONCLUSIONS:
      Plasma BNP testing in a mass screening setting is of limited use for the
      identification of LV hypertrophy patients among hypertensive patients with
      heterogeneous etiology.

PMID- 14643577
TI  - Direct comparison of the effects of valsartan and amlodipine on renal
      hemodynamics in human essential hypertension.
AB  - BACKGROUND: To elucidate the renoprotective mechanism of AT(1)-receptor blockers,
      we compared the effects of the AT(1)-receptor blocker valsartan with those of the
      calcium channel blocker amlodipine on renal hemodynamics and microcirculation.
      METHODS: A total of 58 patients (50.2 +/- 9.0 years) with mild to moderate
      essential hypertension were included in a randomized, double-blind study to
      receive either valsartan (80 to 160 mg) or amlodipine (5 to 10 mg). Renal plasma
      flow (RPF) and glomerular filtration rate (GFR) were measured before and after 8
      weeks of treatment. Glomerular hydrostatic pressure (P(Glo)) and resistances of
      the afferent (R(A)) and efferent (R(E)) arterioles were calculated according to
      the Gomez formulas. RESULTS: Blood pressure control was similar in both groups.
      RPF did not change with either treatment. In contrast, GFR increased with
      amlodipine (+8 +/- 14 mL/min; P <.01) but was preserved with valsartan.
      Amlodipine caused a more marked increase in the R(E)/R(A) ratio than valsartan
      (+0.26 +/- 0.26 v +0.13 +/- 0.24, P <.05), which was paralleled by an increase in
      P(Glo) in patients treated with amlodipine (+1.9 +/- 4.3 mm Hg; P <.05) but not
      in those treated with valsartan. CONCLUSIONS: At similar blood pressure control,
      valsartan maintained GFR and P(Glo), whereas amlodipine led to glomerular
      hyperfiltration and an increase in P(Glo). The results might explain the
      favorable renal outcome with AT(1)-receptor blocker therapy.

PMID- 14643578
TI  - Antihypertensive effects of two fixed-dose combinations of losartan and
      hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with
      ambulatory systolic hypertension.
AB  - BACKGROUND: The efficacy of losartan (L) in combination with hydrochlorothiazide
      (HCTZ) has been demonstrated to reduce blood pressure. However, there are limited
      data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing
      ambulatory systolic blood pressure. The aim of this study was to compare the
      effects of these treatment approaches in patients with ambulatory systolic
      hypertension. METHODS: Patients were randomized to receive L 50 mg (n = 60) or
      HCTZ 12.5 mg (n = 60) for 6 weeks. Patients were then force-titrated to L 50/HCTZ
      12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force
      titrated to HCTZ 25 mg, respectively. Clinic and 24-h ambulatory blood pressure
      (ABP) were measured at baseline and after each 6-week treatment period. RESULTS:
      We found that L 50 and HCTZ 12.5 induced significant and similar decreases in
      clinic and ABP. The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided
      significantly greater decreases in clinic and ABP than did HCTZ monotherapies.
      The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional
      decreases in systolic/diastolic ABP during daytime (-5.3/-2.0 mm Hg; P <.001 and 
      5.8/-3.4 mm Hg; P <.001) and the other periods of the 24-h interval compared with
      the levels achieved by the previous treatment, indicating a clear dose-response
      relationship. However, increasing the dose of HCTZ from 12.5 mg to 25 mg was not
      associated with additional ABP reductions. CONCLUSIONS: Combinations of L 50/HCTZ
      12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ
      monotherapies, with a clear dose-response relationship with regard to ABP. These
      results support the use of ABP monitoring when assessing the efficacy of
      antihypertensive therapies.

PMID- 14643579
TI  - Blood pressure response to hypoxia: role of nitric oxide synthase.
AB  - BACKGROUND: Chronic exposure to hypobaric hypoxia has been shown to increase
      arterial pressure in genetically normal rats. The associated increase in blood
      pressure is unrelated to the hypoxia-induced erythrocytosis and persists
      indefinitely after restoration of normoxia. It is accompanied by a marked
      reduction in urinary excretion of nitric oxide metabolites (NOx) and is
      ameliorated by L-arginine supplementation. In view of the latter observations, we
      hypothesized that hypoxia-induced hypertension may be associated with
      downregulation of NO synthase (NOS). METHODS: Male Sprague Dawley rats were
      randomized to the hypoxic and control groups. Rats assigned to the hypoxic group
      were placed in chambers with air pressure maintained at 390 mm Hg. Animals
      assigned to the control group were kept in the chamber at 760 mm Hg air pressure.
      Animals were kept in their respective conditions for up to 21 days. Group of
      animals were tested at days 2, 3, 7, and 21. RESULTS: The hypoxic group exhibited
      a steady increase in arterial pressure beginning at day 3. This was accompanied
      by a transient increase followed by a significant decline in kidney NOS-I, NOS
      II, and NOS-III abundance. A similar biphasic change was observed with NOS-II and
      NOS-III in the cardiac and vascular tissues. The changes in NOS abundance in the
      given tissues were associated with parallel changes in nitrotyrosine abundance,
      which reflects local NO production. The latter finding provides functional
      evidence for the changes observed in NOS abundance. CONCLUSIONS: Chronic hypoxia
      induced hypertension in rats is associated with marked downregulation of NOS
      isotypes, which can, in part, account for the previously reported L-arginine
      responsive hypertension in this model.

PMID- 14643580
TI  - Oxidative stress in hypertensive,diabetic, and diabetic hypertensive rats.
AB  - BACKGROUND: Reactive oxygen species play a key role in the formation of
      endothelial dysfunction accompanying diabetes mellitus, hypertension, and other
      cardiovascular diseases. METHOD: This study compares oxidative stress (OS) in
      Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), non-insulin
      dependent Cohen Diabetic rats (CDR), and Cohen Rosenthal diabetic hypertensive
      rats (CRDH), a unique animal model of both diabetes and hypertension. The OS was
      evaluated with a newly developed thermochemiluminiscence (TCL) analyzer (Lumitest
      Ltd., Nesher, Israel) that measures the oxidizability (ie, susceptibility to
      oxidation) of a test sample. RESULTS: The TCL oxidizability test results of sera
      from the different rats groups showed a time-dependent increase in TCL of up to
      145% +/- 7% for WKY, 160% +/- 8% for SHR, 179% +/- 12% for CDR, and 226% +/- 15%
      for CRDH. These results were significant: P <.001 for SHR and CDR and P <.0001
      for CRDH in comparison to WKY. Lipid peroxide levels also increased in each
      strain of rats: to 80 +/- 7.8 nmol/mL in WKY, 104 +/- 10.1 nmol/mL in SHR, 110 +/
      9.4 nmol/mL in CDR, and 167 +/- 11.7 nmol/mL in CRDH. These results were also
      significant: P <.001 for SHR, CDR and CRDH in comparison to WKY. CONCLUSION: The
      combination of hypertension and diabetes is accompanied by higher oxidative
      stress than that seen with either disorder alone.

PMID- 14643581
TI  - The effects of allicin on weight in fructose-induced hyperinsulinemic,
      hyperlipidemic, hypertensive rats.
AB  - BACKGROUND: Commercially available garlic preparations in the form of garlic oil,
      garlic powder and pills are widely used for certain therapeutic purposes,
      including lowering blood pressure and improving lipid profile. Despite the
      impressive effects of garlic most studies are limited by lack of controlled
      methods and suitable double-blinding, and by the use of preparations with unknown
      amounts and chemical identification of the active ingredient. Allicin, a
      synthetic preparation of an active constituent of garlic, was found to lower
      blood pressure, insulin, and triglycerides levels in fructose-fed rats. Thus, it
      was considered important to assess its effect on the weight of the animals.
      METHODS: Male Sprague-Dawley rats weighing 240 to 250 g were fed a fructose
      enriched diet consisting of 21% protein, 5% fat, 60% carbohydrate, 0.49% sodium
      and 0.49% potassium for 5 weeks, which produced hyperinsulinemia, hypertension,
      and hypertriglyceridemia. Group I (controls) rats were fed a diet enriched by
      fructose only; group II was given allicin the last 2 weeks, and group III was
      given allicin the first 3 weeks. The three groups consumed the same amount of
      food. Weight was measured at the beginning of the experiment and after 3 and 5
      weeks on the diet. RESULTS: Weight in the control group rose from 249.4 +/- 10.04
      g to 274.5 +/- 15.5 g after 3 weeks and to 306.9 +/- 22.2 g after 5 weeks. Weight
      in group II rose from baseline 259.1 +/- 12.1 g to 306.9 +/- 22.2 g after 3 weeks
      on fructose alone, and declined slightly to 282.4 +/- 17.4 g after 2 weeks of
      allicin (P <.02). In group III, in which the protocol was reversed, the baseline
      weight of 260.4 +/- 13.25 g rose only to 269.8 +/-15.3 g (P <.431) after 3 weeks
      on fructose and allicin. CONCLUSIONS: The control group that was fed a diet
      enriched by fructose alone continued to gain weight, whereas the groups fed
      allicin did not. The difficulty of preventing weight gain after reaching the
      nadir of weight loss underscores the practical value of allicin for weight
      control.

PMID- 14643582
TI  - Volume expansion enhances plasma endothelin-1.
AB  - We hypothesized that acute volume expansion by saline infusion triggers the
      release of endothelin-1. Bolus intravenous saline infusion (8 mL/min) in six
      groups of conscious Wistar rats and spontaneously hypertensive rats did not
      change mean arterial pressure or heart rate (n = 8 to 12). At 1 min after
      infusion, the plasma endothelin-1 level was significantly increased in Wistar
      rats and in spontaneously hypertensive rats by 42% and 61%, respectively
      (unpaired data). In 12 Wistar rats, the endothelin-1 level increased from 0.68 +/
      0.13 to 1.19 +/- 0.17 fmol/mL (mean +/- SEM, P <.0001, paired data). Thus, acute
      volume load by rapid saline infusion increases plasma endothelin-1 levels.
      Vasoconstriction induced by endothelin-1 may counteract enhanced circumferential
      stretch created by volume expansion.

PMID- 14643583
TI  - Digoxin antibody prevents cerebral hemorrhage-induced hypertension.
AB  - BACKGROUND: Brain injury may induce hypertension. Because serum ouabain-like
      compound (OLC) has vasoconstrictor activity, digoxin antibody antihypertensive
      effects were evaluated using an intracerebroventricular (ICV) hemorrhage rat
      model. METHODS: Four ICV infused Wistar rat groups were studied: control; blood;
      blood plus digoxin antibody, and cerebrospinal fluid-like solution. Tail-cuff
      blood pressure, cumulative sodium balance, and serum OLC were measured. RESULTS:
      The ICV blood infusion increased blood pressure (BP) and OLC without sodium
      balance change. Digoxin antibody prevented BP and OLC rise. Blood pressure was
      positively correlated with OLC in blood and blood plus digoxin antibody rats (R =
      0.63; P <.05). CONCLUSIONS: Cerebral hemorrhage increased OLC and BP, which were
      reversed by digoxin antibody administration.

PMID- 14643584
TI  - Tolerability and treatment compliance with angiotensin II receptor antagonists.
AB  - Several studies and intervention trials performed during the past 30 years have
      provided evidence that hypertension-related cardiovascular risk is not
      irreversible. This is because the reduction in blood pressure (BP) induced by
      antihypertensive drugs has been shown to be accompanied by a clear-cut decrease
      in the rate of cardiovascular events and complications. There is also evidence
      that BP control in the population is far from being optimal, and that no more
      than one quarter of treated hypertensive patients display BP values <140/90 mm
      Hg. The reasons for inadequate BP control are multiple, involving a combination
      of factors such as inadequate compliance with treatment, intolerance to side
      effects of currently prescribed drugs, and insufficient clinical use of
      combination drug treatment. This article focuses on three major areas. It first
      provides an overview of the current status of BP control in treated hypertensive
      persons. It then examines the factors potentially responsible for this
      phenomenon, with particular emphasis on the relevance of the so-called
      "compliance factor." Finally it provides an overview of the tolerability and
      compliance profile of the angiotensin II receptor antagonists, a new class of
      antihypertensive drugs characterized by an efficacy and safety profile.

PMID- 14643585
TI  - Experimental evidence for blood pressure-independent vascular effects of high
      sodium diet.
AB  - The two physiologic mechanisms that may be responsible for the adverse
      cardiovascular effects of long-term high sodium diet without increasing blood
      pressure (BP) are increased blood flow and increased extracellular sodium
      concentration. The first dilates arteries, and the second may impact on vascular
      reactivity and growth. The experimental evidence for these two mechanisms was
      critically reviewed, distinguishing between the administration of physiologically
      relevant and potentially toxic doses of dietary sodium. There is evidence that a
      high sodium diet results in dilatation and reduced distensibility of arteries.
      There is also evidence for an increase of plasma sodium concentration during a
      high-sodium diet (2 to 5 mmol/L) that may be sufficient to stimulate vascular
      reactivity and growth. An increase in transmembrane sodium gradient of vascular
      muscle and increased affinity of receptors for agonists may be the underlying
      mechanisms. Further experimental evidence is needed to convince the scientific
      community that lifelong high sodium intake expedites cardiovascular aging and
      reduces life expectancy independently of its effect on BP.

PMID- 14643586
TI  - Diagnosis of renal artery stenosis: combining gadolinimum-enhanced three
      dimensional magnetic resonance angiography with functional magnetic resonance
      pulse sequences.

PMID- 14643587
TI  - Dental composites based on hybrid and surface-modified amorphous calcium
      phosphates.
AB  - The objectives of this study were to prepare hybrid and surface-modified
      amorphous calcium phosphates (ACPs) as fillers for mineral-releasing dental
      composites, and determine whether the mechanical strength of the composites could
      be improved without decreasing their remineralization potential. ACP was
      hybridized with tetraethoxysilane or zirconyl chloride and surface-treated with 3
      methacryloxypropoxytrimethoxy silane (MPTMS) or zirconyl dimethacrylate (ZrDMA).
      Composites fabricated with unmodified ACP (u-ACP), hybrid or surface-modified ACP
      filler and photo-activated Bis-GMA, TEGDMA and 2-hydroxyethyl methacrylate (HEMA)
      (BTH resin), Bis-GMA, TEGDMA, HEMA and MPTMS (BTHS resin) or Bis-GMA, TEGDMA,
      HEMA and ZrDMA (BTHZ resin) were tested for their remineralizing potential and
      biaxial flexure strength (BFS). Ion releases from all composites were
      significantly above the minimum necessary for reprecipitation of apatite. The BFS
      of unfilled polymers was not adversely affected by immersion in saline solutions.
      The BFS of BTH and BTHS composites deteriorated upon soaking. However, BTHZ
      composites were practically unaffected by exposure to saline solutions. Filler
      hybridization resulted in a modest, but significant, improvement in the BFS (up
      to 24%) of BTHZ composites. Heterogeneous distribution of the ACP on disk
      surfaces was detected by the FTIR microspectroscopy analyses. This might have
      been caused by uncontrolled aggregation of ACP particles that appeared to hinder
      interfacial filler/resin interactions and diminish the mechanical strength of
      composites.

PMID- 14643588
TI  - Dry mechanochemical synthesis of hydroxyapatites from DCPD and CaO: influence of
      instrumental parameters on the reaction kinetics.
AB  - Mechanochemistry is a possible route to synthesize calcium deficient
      hydroxyapatite (CDHA) with an expected molar calcium-to-phosphate (Ca/P) ratio +/
      0.01. To optimize the experimental conditions of CDHA preparation from dicalcium
      phosphate dihydrate (DCPD) and calcium oxide by dry mechanosynthesis reaction, we
      performed the kinetic study varying some experimental parameters. This kinetic
      study was carried out with two different planetary ball mills (Retsch or Fritsch
      Instuments). Results obtained with the two mills led to the same conclusions
      although the values of the rate constants of DCPD disappearance and times for
      complete reaction were very different. Certainly, the origin of these differences
      was from the mills used, thus we investigated the influence of instrumental
      parameters such as the mass and the surface area of the balls or the rotation
      velocity on the mechanochemical reaction kinetics of DCPD with CaO. Results show
      that the DCPD reaction rate constant and the inverse of the time for complete
      disappearance of CaO both vary linearly with (i) the square of the rotation
      velocity, (ii) the square of eccentricity of the vial on the rotating disc and
      (iii) the product of the mass by the surface area of the balls. These
      observations comply with theoretical models developed for mechanical alloying.
      The consideration of these four parameters allows the transposition of
      experimental conditions from one mill to another or the comparison between
      results obtained with different planetary ball mills. These instrumental
      parameters have to be well described in papers concerning mechanochemistry or
      when grinding is an important stage in a process.

PMID- 14643589
TI  - Effects of apatite cements on proliferation and differentiation of human
      osteoblasts in vitro.
AB  - Although apatite cement (AC) and sintered hydroxyapatite (s-HAP) are known to
      show good osteoconductivity, it is not clear whether or not the degree of their
      osteoconductivity is the same. In addition, it has not been clarified whether or
      not it is dependent on the type of AC; conventional AC (c-AC), fast-setting AC
      (fs-AC) or anti-washout AC (aw-AC). The aim of this study was to investigate the
      effects of ACs on cultured human osteoblasts, as they may provide a useful index
      of osteoconductivity. Human osteoblasts were cultured on the surfaces of ACs and
      s-HAP, and were evaluated with respect to cell attachment, proliferation, and
      differentiation. We found that ACs and s-HAP showed similar cell attachment. No
      significant difference between ACs and s-HAP was found with respect to the
      proliferation of osteoblasts. In contrast, we found that the differentiation of
      osteoblasts was enhanced on the surface of ACs compared with that of s-HAP.
      However, there was no difference among the types of AC. We therefore concluded
      that AC may show better osteoconductivity than s-HAP, and that osteoconductivity
      of AC may be similar, regardless of the type of AC.

PMID- 14643590
TI  - Bone-like apatite-forming ability and mechanical properties of poly(epsilon
      caprolactone)/silica hybrid as a function of poly(epsilon-caprolactone) content.
AB  - Effect of poly(epsilon-caprolactone) (PCL) content on the bioactivity and
      mechanical properties of PCL/silica hybrid was investigated. The PCL/silica
      hybrids with different PCL contents were prepared through co-condensation
      reaction with triethoxysilane end capped PCL and tetraethyl orthosilicate. The
      higher the PCL content in the hybrid, the lower the apatite-forming rate and
      showed polymer-like ductile-tough fracture behavior. On the contrary, the lower
      the PCL content in the hybrid, the higher the apatite-forming rate and showed
      ceramic-like hard-brittle fracture behavior. At the intermediate PCL content, the
      apatite-forming rate and its mechanical properties showed also intermediate
      behaviors. The highest tensile strength and Young's modulus could be obtained at
      intermediate PCL content and they were around 20 and 600 MPa, respectively, while
      the strain at failure was around 50%. This new kind of hybrid material is likely
      to have the potential to be used as a bone repairing material because of its
      apatite-forming ability and the mechanical properties comparable to human
      cancellous bone.

PMID- 14643591
TI  - Significance of melt-fraction in HVOF sprayed hydroxyapatite particles, splats
      and coatings.
AB  - Microstructure characterization and property evaluation of high velocity oxy-fuel
      (HVOF) sprayed hydroxyapatite (HA) splats and coatings were conducted in the
      present study as a function of the proportion of melting that occurred in HA
      particles during HVOF spray. In vitro behavior of single and folded HA splats in
      simulated body fluid was also investigated. Results showed that phase composition
      of as-sprayed HA coatings was influenced significantly by the melt fraction in
      HVOF sprayed particles. Melt fraction of the HA powders were experimentally
      determined from particle morphology analysis. It was found that the spray
      parameters and starting powder size influenced the melt fraction of the
      particles. In vitro investigation of individual HA splats made from different HA
      particles revealed decisive role of local phase composition in influencing their
      dissolution/precipitation behavior during the test. Furthermore, Raman
      spectroscopy qualitative inspection on the sprayed HA particles (partial melted)
      revealed that thermal decomposition occurred within the melted part rather than
      the unmelted zone. Young's modulus and micro-hardness of the as-sprayed particles
      and coatings were determined using nano-indentation technique. The resolidified
      zone of the sprayed HA particles exhibited an average Young's modulus value of
      41.25 GPa. The measured values ranged from 23.1 to 65.3 GPa. The unmelted part of
      the HA powders showed a markedly narrower range. Young's modulus value of 83.9
      GPa (+/-9.4 GPa) was recorded for this region. This succinctly highlight the
      difference between the unmelted region and melted regions of a HA particle.
      Young's moduli values measured on HVOF coatings were found to mirror the trend
      found in the spheroidised particles and splats with apt fidelity.

PMID- 14643592
TI  - Biomimetic apatite formation on chemically treated titanium.
AB  - Titanium treated in NaOH can form hydroxycarbonated apatite (HCA) after
      exposition in simulated body fluid (SBF). Generally, titanium is covered with a
      passive oxide layer. In NaOH this passive film dissolves and an amorphous layer
      containing alkali ions is formed on the surface. When exposed to SBF, the alkali
      ions are released from the amorphous layer and hydronium ions enter into the
      surface layer, resulting in the formation of Ti-OH groups in the surface. The
      released Na(+) ions increase the degree of supersaturation of the soaking
      solution with respect to apatite by increasing pH, and Ti-OH groups induce
      apatite nucleation on the titanium surface. The acid etching of titanium in HCl
      under inert atmosphere was examined as a pretreatment to obtain a uniform initial
      titanium surface before alkali treatment. Acid etching in HCl leads to the
      formation of a micro-roughened surface, which remains after alkali treatment in
      NaOH. It was shown by SEM, gravimetric and solution analysis that the apatite
      nucleation was uniform and the thickness of precipitated HCA layer increased
      continuously with time. The treatment of titanium by acid etching in HCl and
      subsequently in NaOH is a suitable method for providing the metal implant with
      bone-bonding ability.

PMID- 14643593
TI  - The biocompatibility of crosslinkable copolymer coatings containing sulfobetaines
      and phosphobetaines.
AB  - The comparison of copolymers containing sulfobetaine or phosphobetaine moieties
      for use as potential biocompatible coatings has been investigated. Two
      statistical copolymers were produced by a free radical polymerisation technique,
      one based on a sulfobetaine and the other on a phosphobetaine, both with a silyl
      group component to allow thermal crosslinking after coating. PMMA and glass discs
      were dip-coated with the polymers and their properties were compared to the
      uncoated controls. Bacterial adhesion to these coated materials was assessed
      using Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas
      aeruginosa. Human macrophages and granulocytes were used to assess the adhesion
      and activation of inflammatory cells whilst mouse 3T3 fibroblast cells were used
      to assess the propensity for the materials to support fibroblast cell adhesion.
      In all cases the polymer coatings reduced cell adhesion with respect to the base
      materials. The phosphobetaine-based copolymer coatings were shown to be markedly
      superior to the sulfobetaine-based copolymer coatings.

PMID- 14643594
TI  - Altered responses of chondrocytes to nanophase PLGA/nanophase titania composites.
AB  - Chondrocyte (cartilage-synthesizing cells) cell density and synthesis of select
      intracellular proteins by chondrocytes were investigated on novel nanophase poly
      lactic/glycolic acid (PLGA) and titania composites in the present in vitro study.
      Nanophase PLGA films were created by chemically treating conventional (or micron
      structured) PLGA films with 10N NaOH for 1h. Titania particle dimensions in
      ceramic compacts were controlled by utilizing either conventional (i.e., micron)
      or nanometer grain size titania. Composites of either conventional or nanophase
      PLGA with either conventional or nanophase titania at 70/30wt% were also created.
      Compared to surfaces with a conventional or micron topography, results provided
      the first evidence of stagnant confluent cell densities on nanostructured
      surfaces at time points between 1 and 7 days. Moreover, compared to surfaces with
      a conventional topography, increased chondrocyte intracellular synthesis of
      alkaline phosphatase and chondrocyte expressed protein-68 (proteins that have
      been correlated with the functions of chondrocytes) were observed on nanophase
      PLGA/nanophase titania composites. The present study, thus, provided the first
      evidence of different chondrocyte responses to nanostructured PLGA/nanophase
      titania composites; in light of other reports demonstrating increased functions
      of bone cells on the same materials, such data indicates that further
      investigation of these materials at the bone-cartilage interface should be
      conducted.

PMID- 14643595
TI  - High-throughput investigation of osteoblast response to polymer crystallinity:
      influence of nanometer-scale roughness on proliferation.
AB  - A high-throughput method for analyzing cellular response to crystallinity in a
      polymer material is presented. Variations in crystallinity lead to changes in
      surface roughness on nanometer length scales, and it is shown that cells are
      exquisitely sensitive to these changes. Gradients of polymer crystallinity were
      fabricated on films of poly(L-lactic acid) using a gradient in annealing
      temperature. The resultant morphologies were characterized using an atomic force
      microscope. Root-mean-square (rms) roughness values ranging from 0.5 to 13 nm
      were created on a single sample. MC3T3-E1 osteoblastic cells were cultured for 1,
      3 and 5 d, and the number of cells was measured using automated fluorescence
      microscopy. It is shown that the rate of proliferation on the smooth regions of
      the films is much greater than that on the rough regions, and a monotonic
      variation in rate is observed as a function of roughness. The critical rms
      roughness, above which a statistically significant reduction in rate of
      proliferation occurs, was approximately 1.1 nm. Fluorescence microscopy
      measurements on immunostained cells indicate there is no significant change in
      cell area, the number or type of adhesions formed, or the degree of actin
      polymerization. Results from enzyme-linked immunofluorescence assays indicated
      that there was no detectable change in adhesion protein accessibility, suggesting
      the cells directly respond to substrate topography. The use of the gradient
      library approach yielded the functional dependence of cell proliferation on
      nanometer-scale roughness and gave a sensitive estimate of the critical roughness
      for which a decrease in proliferation is observed.

PMID- 14643596
TI  - Degradation behaviour of self-reinforced 80L/20G PLGA devices in vitro.
AB  - In vitro degradation of self-reinforced PLGA 80L/20G material and bioabsorbable
      stents was studied in artificial urine and phosphate buffer solution (PBS) to
      define if the media have an effect on the degradation rate in urological
      applications. After six weeks, the Mv of the samples immersed in PBS was 40%
      (16.7 kDa) from the initial value and 57% (24.0 kDa) for the samples immersed in
      artificial urine. The strength loss of samples that were immersed in PBS was
      slower when compared with samples in artificial urine. The bending strength of
      samples immersed 15 weeks in artificial urine was 43% (21.7 MPa) of the bending
      strength of samples immersed in PBS (50.9 MPa), and the shear strength was 13%
      (artificial urine 3.7 MPa, PBS 28.8 MPa), respectively. The maximum compression
      force in PBS was slightly over at the initial level after 2 weeks of immersion.
      It decreased to half (102.2N) of the initial value (204.1N) in 8 weeks, and after
      12 weeks it was 25% (50.8 N) of the initial value. The compression force in
      artificial urine was 35% (66.8 N) of the initial value (193.9 N) after 8 weeks.
      In 12 weeks it had lowered to 26 N in artificial urine, which was 14% of the
      initial value. The degradation rate of self-reinforced L-lactic and glycolic acid
      stents in vitro tests in artificial urine was coinciding with our clinical test.
      Based on these results, it is possible to make a sufficiently accurate in vitro
      model for the degradation rate of bioabsorbable polymers for urological
      applications.

PMID- 14643597
TI  - Changes in the surface oxide composition of Co-Cr-Mo implant alloy by macrophage
      cells and their released reactive chemical species.
AB  - We hypothesized in this study that macrophage cells and their released reactive
      chemical species (RCS) alter the surface oxide composition of Co-Cr-Mo alloys in
      vitro. Alloys were prepared to simulate the clinical conditions and incubated for
      3 days in cell culture medium, medium with macrophage cells and medium with
      activated macrophage cells. X-ray photoelectron spectroscopy was used to evaluate
      the elemental and chemical changes of the surface oxide compositions. The as
      polished and passivated specimens exhibited typical Cr(2)O(3) rich surfaces.
      After 3 days in medium, the major metal peaks were masked by proteins from the
      culture medium, as indicated by the increase in N and C peaks. When cultured with
      cells, the Cr peaks reappeared and the O peak increased in intensity. These peak
      intensities increased further when the cells were activated to release NO and
      other RCS. We speculated that the cells reduced protein depositions and RCS may
      have enhanced alloy surface oxides through the oxidation and nitration reactions.
      These data have demonstrated that surface oxide composition varied with in vitro
      environments. Changes in the composition of the alloy surface oxides over time by
      cells are important to the understanding of host-material interactions and in the
      release of alloy corrosion products.

PMID- 14643598
TI  - Geometrically structured implants for cranial reconstruction made of
      biodegradable polyesters and calcium phosphate/calcium carbonate.
AB  - The aim of this study was the development of a processing pathway for
      manufacturing of biodegradable skull implants with individual geometry. The
      implants on the basis of polylactide and calcium phosphate/calcium carbonate were
      prepared by a combination of hot pressing and gas foaming. On the inside, the
      implant consists of a macroporous and faster degradable material (poly(D,L
      lactide)+CaCO3) to allow the ingrowth of bone cells. The pore size is in the
      range of 200-400 microm. On the outside, the implant consists of a compact and
      slower biodegradable material (poly(L-lactide) and calcium phosphate) to ensure
      mechanical stability and protection. To overcome problems like inflammatory
      reactions caused by acidic degradation products of polylactide, the polyester was
      combined with basic filling materials (calcium salts). The filler neutralises the
      lactic acid produced during polymer degradation and increases the bioactivity of
      the material. The stabilised pH was demonstrated by long-term in vitro pH
      studies. Over a time period of 250 d in demineralised water, the pH was in the
      physiological range. The in vitro biocompatibility was shown by cell cultures
      with human osteoblasts. A good proliferation of the cells was observed over the
      whole test period of 4 weeks.

PMID- 14643599
TI  - Human microvascular endothelial cell growth and migration on biomimetic
      surfactant polymers.
AB  - Successful engineering of a tissue-incorporated vascular prosthesis requires
      cells to proliferate and migrate on the scaffold. Here, we report on a series of
      "ECM-like" biomimetic surfactant polymers that exhibit quantitative control over
      the proliferation and migrational properties of human microvascular endothelial
      cells (HMVEC). The biomimetic polymers consist of a poly(vinyl amine) (PVAm)
      backbone with hexanal branches and varying ratios of cell binding peptide (RGD)
      to carbohydrate (maltose). Proliferation and migration behavior of HMVEC was
      investigated using polymers containing RGD: maltose ratios of 100:0, 75:25 and
      50:50, and compared with fibronectin (FN) coated glass (1 microg/cm2). A radial
      Teflon fence migration assay was used to examine HMVEC migration at 12 h
      intervals over a 48 h period. Migration was quantified using an inverted optical
      microscope, and HMVEC were examined by confocal microscopy for actin and focal
      adhesion organization/ arrangement. Over the range of RGD ligand density studied
      (approximately 0.19-0.6 peptides/nm2), our results show HMVEC migration decreases
      with increasing RGD density in the polymer. HMVEC were least motile on the 100%
      RGD polymer (approximately 0.38-0.6 peptides/nm2) with an average migration of
      0.20 mm2/h in area covered, whereas HMVEC showed the fastest migration of 0.48+/
      0.06 mm2/h on the 50% RGD surface ( approximately 0.19-0.30 peptides/nm2). In
      contrast, cell proliferation increased with increasing surface peptide density;
      proliferation on the 50% RGD surface was 1.5%+/-0.06/h compared with 2.2%+/
      0.07/h on the 100% RGD surface. Our results show that surface peptide density
      affects cellular functions such as growth and migration, with the highest peptide
      density supporting the most proliferation but the slowest migration.

PMID- 14643600
TI  - Physical properties of artificial extracellular matrix protein films prepared by
      isocyanate crosslinking.
AB  - Artificial extracellular matrix proteins, genetically engineered from elastin-
      and fibronectin-derived repeating units, were crosslinked with hexamethylene
      diisocyanate in dimethylsulfoxide. The resulting hydrogel films were transparent,
      uniform, and highly extensible. Their tensile moduli depended on crosslinker
      concentration and spanned the range characteristic of native elastin. The water
      content of the films was low ( approximately 27%), but the temperature-dependent
      swelling behavior of the crosslinked materials was reminiscent of the lower
      critical solution temperature property of the soluble polymers.

PMID- 14643601
TI  - Multi-channeled biodegradable polymer/CultiSpher composite nerve guides.
AB  - Innovative methods to fabricate porous, biodegradable conduits were developed to
      produce nerve guides with multiple longitudinally aligned channels. The geometry
      of the nerve guide's channels was designed to be appropriate for harboring
      neurite extension. Both the coated mandrel and mandrel adhesion techniques permit
      flexibility in the number of channels, channel organization, and channel
      diameters. In this study, the composite nerve guides were comprised of
      poly(caprolactone) (PCL) and porous collagen-based beads (CultiSphers). The
      incorporation of the collagenous beads results in enhanced cortical neuron
      adhesion, viability, and neurite extension as compared to PCL alone.
      Additionally, Schwann cell studies indicated that the PCL/CultiSpher composite is
      a suitable substrate for cell adhesion. Mechanical properties of the
      PCL/CultiSpher material and in vitro degradation rates indicate the potential
      usefulness of this novel composite for use in the fabrication of nerve guides.

PMID- 14643602
TI  - Hydroxyapatite/poly(epsilon-caprolactone) composite coatings on hydroxyapatite
      porous bone scaffold for drug delivery.
AB  - Hydroxyapatite (HA) porous scaffold was coated with HA and polycaprolactone (PCL)
      composites, and antibiotic drug tetracycline hydrochloride was entrapped within
      the coating layer. The HA scaffold obtained by a polymeric reticulate method,
      possessed high porosity ( approximately 87%) and controlled pore size (150-200
      microm). Such a well-developed porous structure facilitated usage in a drug
      delivery system due to its high surface area and blood circulation efficiency.
      The PCL polymer, as a coating component, was used to improve the brittleness and
      low strength of the HA scaffold, as well to effectively entrap the drug. To
      improve the osteoconductivity and bioactivity of the coating layer, HA powder was
      hybridized with PCL solution to make the HA-PCL composite coating. With
      alteration in the coating concentration and HA/PCL ratio, the morphology,
      mechanical properties, and biodegradation behavior were investigated. Increasing
      the concentration rendered the stems thicker and some pores to be clogged; as
      well increasing the HA/PCL ratio made the coating surface be rough due to the
      large amount of HA particles. However, for all concentrations and compositions,
      uniform coatings were formed, i.e., with the HA particles being dispersed
      homogeneously in the PCL sheet. With the composite coating, the mechanical
      properties, such as compressive strength and elastic modulus were improved by
      several orders of magnitude. These improvements were more significant with
      thicker coatings, while little difference was observed with the HA/PCL ratio. The
      in vitro biodegradation of the composite coatings in the phosphate buffered
      saline solution increased linearly with incubation time and the rate differed
      with the coating concentration and the HA/PCL ratio; the higher concentration and
      HA amount caused the increased biodegradation. At short period (<2 h), about 20
      30% drug was released especially due to free drug at the coating surface.
      However, the release rate was sustained for prolonged periods and was highly
      dependent on the degree of coating dissolution, suggesting the possibility of a
      controlled drug release in the porous scaffold with HA+PCL coating.

PMID- 14643603
TI  - Electrospinning of silk fibroin nanofibers and its effect on the adhesion and
      spreading of normal human keratinocytes and fibroblasts in vitro.
AB  - An electrospinning method was used to fabricate silk fibroin (SF) nanofiber
      nonwovens for cell culture of normal human keratinocytes and fibroblasts. The
      electrospinning of regenerated SF was performed with formic acid as a spinning
      solvent. For insolubilization, as-spun SF nanofiber nonwovens were chemically
      treated with an aqueous methanol solution of 50%. Morphology and microstructure
      of as-spun and chemically treated SF nanofibers were investigated by scanning
      electron microscopy and mercury porosimetry. As-spun SF nanofibers exhibited a
      circular cross-section with a smooth surface. From the image analysis, they had
      an average diameter of 80 nm and their diameters ranged from 30 to 120 nm. During
      the chemical treatment for 60 min, porosity of nonwovens composed of SF
      nanofibers decreased from 76.1% up to 68.1%. To assay the cytocompatibility and
      cell behavior onto the electrospun SF nanofibers, cell attachment and spreading
      of normal human keratinocytes and fibroblasts seeded on the SF nanofibers and
      interaction between cells and SF nanofibers were studied. Cell morphology on SF
      nanofibers was examined by scanning electron microscopy. Our results indicate
      that the SF nanofibers may be a good candidate for the biomedical applications,
      such as wound dressing and scaffolds for tissue engineering.

PMID- 14643604
TI  - Contractile forces generated by articular chondrocytes in collagen
      glycosaminoglycan matrices.
AB  - The objective of the study was to directly measure the force of contraction of
      adult articular chondrocytes and to examine their contractile behavior in
      collagen-glycosaminoglycan analogs of extracellular matrix by live cell imaging
      in vitro. The contractile forces generated by passages 2 and 3 adult canine
      articular chondrocytes were measured using a cell force monitor. The contractile
      behavior of the cells was also directly imaged as they were cultured in collagen
      glycosaminoglycan scaffolds. Passage 2 cells seeded in a collagen
      glycosaminoglycan scaffold were capable of generating a force of 0.3 nN/cell.
      Chondrocytes subcultured through a third passage generated a force twice that
      level, paralleling the increase in the alpha-smooth muscle actin (SMA) content of
      the cells as demonstrated by Western blot analysis. Treatment of passage 3 cells
      with staurosporine reduced the force of contraction by approximately one-half,
      reflecting the effects of this agent in reducing the SMA content of the cells and
      disrupting the microfilaments. These values compare with 1 nN previously reported
      for lapine dermal fibroblasts of passage 5-7, using the same apparatus. Direct
      live cell imaging documented the contractile behavior of the articular
      chondrocytes in the collagen-glycosaminoglycan matrix in the time frame in which
      the force was directly measured in the cell force monitor. This imaging
      demonstrated how the cells acted individually and in unison to buckle the
      collagen struts making up the matrix. Adult articular chondrocytes are capable of
      generating a SMA-enabled force of contraction sufficient to model extracellular
      matrix molecules.

PMID- 14643605
TI  - Decreased functions of astrocytes on carbon nanofiber materials.
AB  - Carbon nanofibers possess excellent conductivity properties, which may be
      beneficial in the design of more effective neural prostheses; however, limited
      evidence on their cytocompatibility properties currently exists. The objective of
      the present in vitro study was to determine cytocompatibility properties of
      formulations containing carbon nanofibers pertinent to neural implant
      applications. Substrates were prepared from four different types of carbon
      fibers, two with nanoscale diameters (nanophase, or less than or equal to 100 nm)
      and two with conventional diameters (or greater than 100 nm). Within these two
      categories, both a high and a low surface energy fiber were investigated and
      tested. Carbon fibers were compacted in a manual hydraulic press via a uniaxial
      loading cycle. Astrocytes (glial scar tissue-forming cells) were seeded onto the
      substrates for adhesion, proliferation, and long-term function studies (such as
      total intracellular protein and alkaline phosphatase activity). Results provided
      the first evidence that astrocytes preferentially adhered and proliferated on
      carbon fibers that had the largest diameter and the lowest surface energy. Based
      on these results, composite substrates were also formed using different weight
      percentages (0-25 wt%) of the nanophase, high surface energy fibers in a
      polycarbonate urethane matrix. Results provided the first evidence of decreased
      adhesion of astrocytes with increasing weight percents of the high surface energy
      carbon nanofibers in the polymer composite; this further demonstrates that
      formulations containing carbon fibers in the nanometer regime may limit astrocyte
      functions leading to decreased glial scar tissue formation. Positive interactions
      with neurons, and, at the same time, limited astrocyte functions leading to
      decreased gliotic scar tissue formation are essential for increased neuronal
      implant efficacy.

PMID- 14643606
TI  - Development and characterisation of silver-doped bioactive glass-coated sutures
      for tissue engineering and wound healing applications.
AB  - A novel silver-doped bioactive glass powder (AgBG) was used to coat resorbable
      Vicryl (polyglactin 910) and non-resorbable Mersilk surgical sutures, thereby
      imparting bioactive, antimicrobial and bactericidal properties to the sutures.
      Stable and homogeneous coatings on the surface of the sutures were achieved using
      an optimised aqueous slurry-dipping technique. Dynamic mechanical analysis (DMA)
      was used to investigate the viscoelastic parameters of storage modulus and
      tandelta and thermal transitions of the as-received and composite (coated)
      sutures. The results generally showed that the bioactive glass coating did not
      affect the dynamic mechanical and thermal properties of the sutures. The in vitro
      bioactivity of the sutures was tested by immersion in simulated body fluid (SBF).
      After only 3 days of immersion in SBF, bonelike hydroxyapatite formed on the
      coated suture surfaces, indicating their enhanced bioactive behaviour. Resorbable
      sutures with bioactive coatings as fabricated here, in conjunction with 3-D
      textile technology, may provide attractive materials for producing 3-D scaffolds
      with controlled porosities for tissue engineering applications. The bactericidal
      properties imparted by the Ag-containing glass coating open also new
      opportunities for use of the composite sutures in wound healing and body wall
      repair.

PMID- 14643607
TI  - Improving the expansion and neuronal differentiation of mesenchymal stem cells
      through culture surface modification.
AB  - Poly-D-lysine, poly-L-lysine, collagen, laminin, fibronectin, and Matrigel were
      compared with standard tissue grade polystyrene for their impact on the expansion
      and neuronal differentiation of mesenchymal stem cells (MSCs). Among these
      substrates, adsorption of Matrigel at 5 microg/cm2 did not enhance cell
      proliferation but gave rise to the highest percentage of MSC-derived neuron-like
      cells with the best morphological differentiation. Matrigel at a higher coating
      density of 50 microg/cm2 not only further enhanced the differentiation but also
      significantly improved cell expansion. In contrast, poly-D-lysine did not
      effectively support the growth of MSCs. Hence the expansion and neuronal
      differentiation of MSCs both depend on surface properties of the culture
      substrate. These results could lead to a culture process with improved yield of
      MSC-derived neuron-like cells and to novel biomaterials for tissue engineering.

PMID- 14643608
TI  - In situ crosslinkable hyaluronan hydrogels for tissue engineering.
AB  - We describe the development of an injectable, cell-containing hydrogel that
      supports cell proliferation and growth to permit in vivo engineering of new
      tissues. Two thiolated hyaluronan (HA) derivatives were coupled to four
      alpha,beta-unsaturated ester and amide derivatives of poly(ethylene glycol) (PEG)
      3400. The relative chemical reactivity with cysteine decreased in the order PEG
      diacrylate (PEGDA)>>PEG-dimethacrylate>PEG-diacrylamide>PEG-dimethacrylamide. The
      3-thiopropanoyl hydrazide derivative (HA-DTPH) was more reactive than the 4
      thiobutanoyl hydrazide, HA-DTBH. The crosslinking of HA-DTPH with PEGDA in a
      molar ratio of 2:1 occurred in approximately 9 min, suitable for an in situ
      crosslinking applications. The in vitro cytocompatibility and in vivo
      biocompatibility were evaluated using T31 human tracheal scar fibroblasts, which
      were suspended in medium in HA-DTPH prior to addition of the PEGDA solution. The
      majority of cells survived crosslinking and the cell density increased tenfold
      during the 4-week culture period in vitro. Cell-loaded hydrogels were also
      implanted subcutaneously in the flanks of nude mice, and after
      immunohistochemistry showed that the encapsulated cells retained the fibroblast
      phenotype and secreted extracellular matrix in vivo. These results confirm the
      potential utility of the HA-DTPH-PEGDA hydrogel as an in situ crosslinkable,
      injectable material for tissue engineering.

PMID- 14643609
TI  - Self-assembled extracellular matrix protein networks by microcontact printing.
AB  - Physiological patterns of the extracellular matrix protein, laminin-1, were
      obtained on glass substrates by physisorption-assisted microcontact printing.
      Besides the well-retained antigenicity confirmed by indirect immunofluorescence
      assays, we investigated the supramolecular organization of the proteins by atomic
      force microscopy. We found the characteristic protein self-assembling in
      polygonal networks with well-defined sub-100 nm quaternary structures of laminin.
      The formation of these physiological mesh-like protein matrices was obtained by
      means of one-step soft lithography without any preliminary functionalization of
      glass, which can be exploited for many possible applications for cell cultures
      and biomolecular devices.

PMID- 14643610
TI  - Layer-by-layer microfluidics for biomimetic three-dimensional structures.
AB  - Due to the complex structures of living systems, with size scales spanning from
      the micron to millimeter range, the use of microtechnology to recreate in vivo
      like architecture has exciting potential applications. However, most microscale
      systems are two-dimensional, and few three-dimensional (3-D) systems are being
      explored. We have developed a versatile technique, combining surface engineering
      with layer-by-layer microfluidics technology, to create a 3-D microscale
      hierarchical tissue-like structure. The process involves immobilization of a cell
      matrix assembly, cell-matrix contraction, and pressure-driven microfluidic
      delivery. An aminopropyltriethoxysilane-glutaraldehyde activated chip is used to
      effectively immobilize the cell-matrix assemblies while maintaining cell
      viability. Pressure-driven microfluidics is applied to transport cells-matrices
      with controlled flow rates, determined from dynamic flow imaging. By taking
      advantage of the contraction of the biopolymer matrices by cells, layer-by-layer
      microfluidics can be used to build multilayers of cell-matrix inside a
      microchannel and the thickness of each layer can be controlled down to microscale
      dimensions. Confocal and electron microscopy images of the final structure show a
      hierarchical layered cellular configuration composed of heterogeneous biomimetic
      materials. For a model system, a biomimetic arterial structure is formed using
      three types of vascular cells to mimic the 3-tunic structure found in vivo. This
      approach provides solutions to fabricate hierarchical "neotissues" with
      controlled microarchitectures and 3-D configurations of multiple cell types.

PMID- 14643612
TI  - Sintered hydroxyfluorapatites. Part I: sintering ability of precipitated solid
      solution powders.
AB  - The presence of fluoride within apatites occurring naturally within the body
      provides the basis for investigating the sintering ability of fluoride containing
      hydroxyapatites for use as biomaterials. Hydroxyfluorapatites were synthesized
      and then calcined to produce a 0%, 20%, 40%, 60%, 80% and 100% replacement of the
      hydroxyl ions with fluoride in the hydroxyapatite structure. Fluoride ion
      occupancy within the apatites was found to be about 90% of the anticipated value.
      Pycnometry results revealed a constant true density for powders of low to medium
      fluoride content followed by a rapid increase to the fluorapatite composition.
      Powders were uniaxially pressed, cold-isostatically pressed and sintered at 1150
      degrees C, 1200 degrees C and 1250 degrees C. All hydroxyfluorapatite powders
      displayed a comparable ability for densification except when hydroxyl groups and
      fluoride ions were present at a comparable concentration. The grain size revealed
      that this composition also exhibited the smallest grain size and displayed the
      highest activation energy for grain growth. The lower diffusion created by
      similar amounts of fluoride and hydroxide within the lattice decreases grain
      growth and densification.

PMID- 14643611
TI  - Studies on bone marrow stromal cells affinity of poly (3-hydroxybutyrate-co-3
      hydroxyhexanoate).
AB  - The objective of this study is to investigate the biocompatibility of poly (3
      hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with bone marrow stromal cells in
      vitro. The adsorption of fibronectin on the material was studied by enzyme-linked
      immunosorbent assay. After bone marrow stromal cells were seeded and cultured on
      PHBHHx, their proliferation was investigated by MTT. Differentiation of the cells
      was assessed by measuring alkaline phosphatase activity and by histochemical
      assay. The wettability and thermal property of PHBHHx films were also studied by
      contact angle goniometer, thermogravimetry and differential scanning calorimetry,
      respectively. The results show that bone marrow stromal cells can attach,
      proliferate and differentiate into osteoblasts on PHBHHx films. These results
      suggest that PHBHHx has good affinity with bone marrow stromal cells and may have
      potential applications in bone tissue engineering.

PMID- 14643613
TI  - Sintered hydroxyfluorapatites. Part II: mechanical properties of solid solutions
      determined by microindentation.
AB  - Fluoride substitution within hydroxyapatite is an important occurrence for
      biological apatites and is a promising approach for the chemical modification of
      synthetic hydroxyapatite. Limited information on the influence of fluoride
      substitution for hydroxyl groups on the mechanical properties has provided the
      rationale for this study. Hydroxyfluorapatites with 0%, 20%, 40%, 60%, 80% and
      100% replacement of hydroxyl groups with fluoride ions were assessed for
      hardness, elastic modulus, fracture toughness and brittleness using
      microindentation of sintered pellets. The production of samples with a similar
      grain size and density allowed the influence of fluoride on mechanical properties
      to be determined. It was found that the hardness remains unaffected until 80%
      replacement of hydroxyl groups with fluoride, after which the hardness rapidly
      increases. The elastic modulus increases linearly with fluoride content. Fracture
      toughness is improved with fluoride incorporation into the lattice and reaches a
      peak of 1.8 for a 95% dense sintered pellet with a 60% fluoride replacement,
      followed by a rapid decrease at higher fluoride concentrations. The brittleness
      index is lowered to a minimum at 60%, after which a rapid increase occurs. High
      fluoride levels are unfavourable from a mechanical perspective, are not
      recommended for biomaterials, and can lead to a higher incidence of fracture
      where sodium fluoride, for treatment of osteoporosis, may produce a highly
      fluoridated hydroxyapatite.

PMID- 14643614
TI  - Sintered hydroxyfluorapatites. Part III: sintering and resultant mechanical
      properties of sintered blends of hydroxyapatite and fluorapatite.
AB  - The presence of chemically dissimilar apatites occurs widely in biological
      systems as a result of exposure to chemically enriched media, but also to
      optimize the mechanical properties. The use of mechanical blends of apatites can
      be used to manufacture high temperature processed fluoride containing
      hydroxyapatites with improved properties. Mechanical blends of fluorapatite and
      hydroxyapatite were produced with 0%, 20%, 40%, 60%, 80% and 100% fluorapatite.
      Pellets were sintered at 1150 degrees C, 1200 degrees C and 1250 degrees C and
      the density determined by the Archimedes method. Mechanical properties including
      hardness, elastic modulus and fracture toughness were measured using indentation.
      It was found that mechanical blends of 150 nm sized hydroxyapatite and 300 nm
      sized fluorapatite lead to solid solutions after sintering. The mechanical blends
      do not sinter as effectively as homogeneous hydroxyfluorapatite solid solutions
      and exhibit a minimum density at 80 wt.% fluorapatite. The hardness, elastic
      modulus and brittleness decreases with a higher flourapatite content, attributed
      primarily to a decrease in density. The higher fracture toughness for mechanical
      blends indicates that these materials are more crack resistant and provide a
      means for improving mechanical properties.

PMID- 14643615
TI  - Development of alginate wound dressings linked with hybrid peptides derived from
      laminin and elastin.
AB  - We designed hybrid peptides, SIRVXVXPG (X: A or G), from a laminin-derived
      peptide, SIKVAV, and an elastin-derived peptide, VGVAPG, and tried to develop new
      alginate dressings linked covalently with the hybrid peptides. First, we examined
      the effectiveness of the hybrid peptides for cell attachment and proliferation
      using normal human dermal fibroblasts (NHDF) in vitro. The hybrid peptides
      promoted attachment of NHDF, whereas neither Ac-KSIKVAV nor Ac-KVGVAPG promoted
      attachment. Although all the peptides we examined promoted the proliferation of
      NHDF to some extent, the hybrid peptide-coated plates showed strong NHDF
      proliferative activity, compared with the other peptide. Next, we created
      alginate dressings linked with some of these peptides and examined their
      effectiveness in wound healing using a rabbit ear skin defect model in vivo. Nine
      days after operation, ears with the alginate dressings linked with the hybrid
      peptides showed significantly greater epithelialization and a larger volume of
      regenerated tissue compared to those treated with SIVAV-linked, VGVAPG-linked and
      unlinked alginate dressings. These new alginate dressings linked with the hybrid
      peptides could be promising dressings especially for wounds with impaired
      healing.

PMID- 14643616
TI  - Effect of fabrication pressure on the fatigue performance of Cemex XL acrylic
      bone cement.
AB  - During a cemented arthroplasty, the prepared polymerizing dough of acrylic bone
      cement is subjected to pressurization in a number of ways; first, during delivery
      into the freshly prepared bone bed, second, during packing in that bed (either
      digitally or with the aid of a mechanical device), and, third, during the
      insertion of the prosthesis. Only a few studies have reported on the influence of
      the level of pressurization experienced during these events (which, depending on
      the cementing technique used, has been put at between 8 and 273 kPa) on various
      properties of the cement. That was the focus of the present study, in which the
      fully reversed tension-compression (+/-15 MPa; 5 Hz) fatigue lives (expressed as
      number of cycles to fracture, N(f)) of rectangular cross-sectioned "dog-bone"
      specimens (Type V, per ASTM D 638) fabricated from Cemex XL cement, at pressure
      applied continuously to the cement dough during curing in the specimen mold,
      p=75,150, and 300 kPa, were determined. The N(f) results were analyzed using the
      linearized transformation of the three-parameter Weibull relationship to obtain
      estimates of the Weibull mean, N(WM), which was taken to be the index of fatigue
      performance of the specimen set. Over the range of p studied, N(WM) increased as
      p increased (for example, from 329,118 cycles when p was 75 kPa to 388,496 cycles
      when p was 300 kPa); however, the increase was not significant over any pair of p
      increment steps (Mann-Whitney U-test; alpha<0.05).

PMID- 14643617
TI  - Relationship between biomedical catheter surface properties and lubricity as
      determined using textural analysis and multiple regression analysis.
AB  - In this study, the surface properties of and work required to remove 12
      commercially available and developmental catheters from a model biological medium
      (agar), a measure of catheter lubricity, were characterised and the relationships
      between these properties were examined using multiple regression and correlation
      analysis. The work required for removal of catheter sections (7 cm) from a model
      biological medium (1% w/w agar) were examined using tensile analysis. The water
      wettability of the catheters were characterised using dynamic contact angle
      analysis, whereas surface roughness was determined using atomic force microscopy.
      Significant differences in the ease of removal were observed between the various
      catheters, with the silicone-based materials generally exhibiting the greatest
      ease of removal. Similarly, the catheters exhibited a range of advancing and
      receding contact angles that were dependent on the chemical nature of each
      catheter. Finally, whilst the microrugosities of the various catheters differed,
      no specific relationship to the chemical nature of the biomaterial was apparent.
      Using multiple regression analysis, the relationship between ease of removal,
      receding contact angle and surface roughness was defined as: Work done (N
      mm)=17.18+0.055 Rugosity (nm)-0.52 Receding contact angle ( degrees ) (r=0.49).
      Interestingly, whilst the relationship between ease of removal and surface
      roughness was significant (r=0.48, p=0.0005), in which catheter lubricity
      increased as the surface roughness decreased, this was not the case with the
      relationship between ease of removal and receding contact angle (r=-0.18,
      p>0.05). This study has therefore uniquely defined the contributions of each of
      these surface properties to catheter lubricity. Accordingly, in the design of
      urethral catheters, it is recommended that due consideration should be directed
      towards biomaterial surface roughness to ensure maximal ease of catheter removal.
      Furthermore, using the method described in this study, differences in the
      lubricity of the various catheters were observed that may be apparent in their
      clinical use.

PMID- 14643618
TI  - Roughness induced dynamic changes of wettability of acid etched titanium implant
      modifications.
AB  - Dynamic contact angle analysis (DCA) was used to investigate time-dependent
      wettability changes of sandblasted and acid-etched commercially pure (cp)
      titanium (Ti) implant modifications during their initial contact with aqueous
      systems compared to a macrostructured reference surface. Surface topography was
      analyzed by scanning electron microscopy and by contact stylus profilometry. The
      microstructured Ti surfaces were found to be initially extremely hydrophobic.
      This hydrophobic configuration can shift to a completely wettable surface
      behavior with water contact angles of 0 degrees after the first emersion loop
      during DCA experiments. It is suggested that a hierarchically structured surface
      topography could be responsible for this unexpected wetting phenomenon. Roughness
      spatial and hybrid parameters could describe topographical features interfering
      with dynamic wettability significantly better than roughness height parameters.
      The Ti modifications which shift very sudden from a hydrophobic to a hydrophilic
      state adsorbed the highest amount of immunologically assayed fibronectin. The
      results suggest that microstructuring greatly influences both the dynamic
      wettability of Ti implant surfaces during the initial host contact and the
      initial biological response of plasma protein adsorption. The microstructured
      surfaces, once in the totally wettable configuration, may improve the initial
      contact with host tissue after implantation, due to the drastically increased
      hydrophilicity.

PMID- 14643620
TI  - Preparation of acrylic grafted chitin for wound dressing application.
AB  - Chitin grafted with poly(acrylic acid) (chitin-PAA) was prepared with the aim of
      obtaining a hydrogel characteristic for wound dressing application. The chitin
      PAA films were synthesized at various acrylic acid feed contents to investigate
      its effect on water sorption ability. Acrylic acid (AA) was first linked to
      chitin, acting as the active grafting sites on the chain that was further
      polymerized to form a network structure. The evidences of grafting were found
      from FTIR and solid state 13C NMR spectra. The TGA results exhibited the high
      degradation temperature of the grafted product suggesting the formation of a
      network structure. The degree of swelling (DS) of chitin-PAA films was found in
      the range of 30-60 times of their original weights depending upon the monomer
      feed content. The chitin-PAA film with 1:4 weight ratio of chitin:AA, possessed
      optimal physical properties. The cytocompatibility of the film was investigated
      with a cell line of L929 mouse fibroblasts. The morphology and behavior of the
      cells on the chitin-PAA film were determined after different time periods of
      culture up to 14 days. The L929 cells proliferated and attached well onto the
      film. These results suggested that the 1:4 chitin-PAA has a potential to be used
      as a wound dressing.

PMID- 14643621
TI  - Health and choice: reconciliation needed?

PMID- 14643619
TI  - In vivo behavior of three different injectable hydraulic calcium phosphate
      cements.
AB  - Two dicalcium phosphate dihydrate (DCPD) hydraulic cements and one apatite
      hydraulic cement were implanted in epiphyseal and metaphyseal, cylindrical bone
      defects of sheep. The in vivo study was performed to assess the biocompatibility
      of the DCPD cements, using the apatite cement as control. After time periods of
      2, 4 and 6 months the cement samples were clinically and histologically
      evaluated. Histomorphometrically the amount of new bone formation, fibrous tissue
      and the area of remaining cement were measured over time. In all specimens, no
      signs of inflammation were detectable either macroscopically or microscopically.
      All cements were replaced by different amounts of new bone. The two DCPD-cements
      showed the highest new bone formation and least cement remnants at 6 months,
      whereas the apatite was almost unchanged over all time periods.

PMID- 14643622
TI  - Socio-economic inequalities in health expectancy in Belgium.
AB  - Various international studies have demonstrated socio-economic differences in
      health. Linking the 1991 Census to the National Register and using the Health
      Interview Survey 1997 has enabled assessment of the association between the level
      of education and health in Belgium using the composite indicator 'health
      expectancy'. The Sullivan method was used to calculate health expectancy on the
      basis of current probability of death and prevalence of perceived health. Two
      measures of educational attainment were used: absolute educational attainment and
      the position on a relative hierarchical educational scale obtained by a
      regression-based method. The latter measure enables international comparisons.
      Differences in health expectancy by education were spread over the whole range of
      the educational hierarchy, and were consistently larger among females than males.
      At 25 years of age, the difference in health expectancy between different levels
      of education reached up to 17.8 and 24.7 years in males and females,
      respectively. Compared with people with the highest educational attainment, males
      and females at the lowest level of education spent more than 10 and 20 additional
      years in poor perceived health, respectively. Between ages 25 and 75 years, the
      difference in health expectancy between people with the lowest and highest levels
      of education was 17 years among males and 21 years among females. Compared with
      people at the top of the relative educational scale, males and females at the
      bottom of the scale had 13.6 and 19.7 additional years in poor perceived health,
      respectively. The conclusions of this study in Belgium are consistent with
      studies in other countries. People with a low level of education have shorter
      lives than people with a higher level of education. They also have fewer years in
      good perceived health, and can expect more years in poor health in their shorter
      lives. The inequality in health expectancy seems to be greater in females than
      males.

PMID- 14643623
TI  - Health inequalities in Seville, Spain: use of indicators of social deprivation
      and mortality in small areas.
AB  - OBJECTIVES: To analyse the spatial distribution of social structure and mortality
      in Seville, and to examine the association between various social indicators and
      mortality. METHODS: Small areas of the city were typified on the basis of four
      social indicators, which were used to derive a social index. Overall mortality
      and cause of death were studied in two age groups (1+years and 1-64 years).
      Pearson's correlation coefficient was used to examine the relationship between
      the social indicators and mortality. RESULTS: Significant social and mortality
      differences, particularly in premature mortality of males, were found between the
      areas studied. However, when the basic health zones are grouped together by
      social level, these differences in mortality are not so clear. The social
      indicators that correlate most closely with mortality are unemployment and
      illiteracy. When the social index is used, the correlations are weaker. Premature
      death from trauma in males presents the highest coefficient of correlation with
      unemployment and illiteracy. CONCLUSIONS: The social index used in the present
      study places less emphasis on material differences than those used by Townsend et
      al. and Carstairs and Morris. Also, it was not possible to study mortality by
      individual neighbourhoods in this study. Both factors could have influenced the
      finding that the correlations between both types of indicator are weaker with the
      social index than with unemployment and illiteracy.

PMID- 14643624
TI  - Comparison of health-seeking behaviour between poor and better-off people after
      health sector reform in Cambodia.
AB  - This study compared health-seeking behaviour between poor and better-off people
      after health sector reform in Cambodia. The survey was conducted in the Prek Dach
      Health Centre coverage area, which is located in South-east Cambodia. The study
      population consisted of 257 housewives of reproductive age, selected at random.
      Data were collected through household surveys with a structured questionnaire.
      Data collected included socio-demographic information on the housewives, as well
      as episodes of illness of family members within 30 days prior to the survey. Two
      indicators, the floor area of living space and a rating scale on asset ownership,
      were used to identify poor and very poor people. When a family member became ill,
      subjects most often used home remedies as a first step, followed by self
      medication. Subsequently, people used self-medication or the private health
      sector. Very poor people used the health centre more often than better-off people
      as a first step. For the second step, use of the health centre was also high
      among the poor compared with better-off people, although the difference was not
      statistically significant. Keeping the treatment fees low and abolishing informal
      fees maintained the affordability of health-centre services for the poor.
      However, this benefit diminished quickly with distance from the health centre.
      The significant difference between poor and better-off people disappeared for
      villages situated more than 2 km from the health centre. Thus, the health centre
      in the studied area was shown to be effective in providing primary health care to
      the economically disadvantaged, but only within a limited geographic area.

PMID- 14643625
TI  - The effects of a 12-week group exercise programme on physiological and
      psychological variables and function in overweight women.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of a 12-week
      functional exercise programme on overweight women. METHODS: Twenty-six subjects
      (n=13 exercisers, n=13 controls) aged (mean+/-SD) 63 (+/-4) years completed the
      study. The exercise sessions were carried out twice each week for 12 weeks. The
      variables measured were body mass, body mass index, skin-fold thickness, resting
      blood pressure, total blood cholesterol, chair rise, timed 'up and go' test, 20-m
      walk,lifting a 1- and a 2-kg bag on to a shelf, stair walking, 'sit and reach'
      flexibility test, Life Satisfaction Index and Physical Self-perception Profile
      for Older Adults. The exercise sessions consisted of 40-min sessions during which
      the subjects performed aerobic and strength exercises. RESULTS: Paired analyses
      showed that body mass, body mass index, blood pressure (systolic and diastolic
      values), 'up and go' time, time to complete a 20-m walk, time to lift a 1- and a
      2-kg bag with both the right and left arms onto a shelf, and stair climbing-total
      time and ascent time-decreased significantly in the exercise group. Also, the
      exercise group improved their Life Satisfaction Index score significantly
      compared with the control group. CONCLUSIONS: The results indicate that a
      functional exercise programme has the potential to improve performance in a
      number of physiological variables and functional activities in overweight women.
      The exercise programme enhanced life satisfaction.

PMID- 14643626
TI  - The relationship between parental nutritional status and overweight
      children/adolescents in Rio de Janeiro, Brazil.
AB  - BACKGROUND: The association between overweight parents and overweight
      children/adolescents was investigated in Rio de Janeiro, Brazil between 1995 and
      1996, controlling for the influence of socio-economic and demographic factors.
      METHODS: Data were obtained from a two-stage, residence-based, random sample
      survey of children and adolescents aged 6-19 years and their parents. Body mass
      index (BMI) was used to classify nutritional status. Initially, a logistic
      regression model was built, using an indicator of parental weight (maternal BMI)
      as one of the independent variables and the child/adolescent's BMI as the
      dependent variable. Following that, the association between socio-economic and
      demographic variables and overweight children/adolescents was analysed in a
      univariate analysis. These variables were pre-selected for inclusion in the
      logistic model, provided that their levels of statistical significance were below
      P=0.25, and were added to the model individually according to the order of
      association strength in the univariate analysis. Finally, variables were retained
      in this model at a significance level of P=0.05. RESULTS: This study found that
      20.7% of girls and 26.9% of boys were overweight, with a larger prevalence among
      children aged less than 9 years. In addition to maternal BMI, the predictors of
      overweight children and adolescents were age, gender and the number of people in
      a house. CONCLUSIONS: These results demonstrate the relationship between maternal
      nutritional status and overweight children and adolescents, suggesting that
      obesity-prevention programmes should be focused on the family.

PMID- 14643627
TI  - Refugee participation in health relief services during the post-emergency phase
      in Tanzania.
AB  - INTRODUCTION: While community participation in health activities has been
      examined extensively after Alma-Ata, few studies have focused on beneficiary
      participation in health services in a humanitarian disaster relief programme.
      This research scrutinized refugee participation in encamped health services,
      explored its achievement, and identified the further needs of refugees in pursuit
      of enhanced health services in the camp. METHODS: The study was performed at
      Lugufu Camp, Tanzania, where a health information team (HIT) of Congolese
      refugees actively participated in health services. Structured questionnaires were
      used for this cross-sectional observational study, covering three types of
      respondents: i.e. (1) systematically selected refugee community members (n=576);
      (2) all HIT members (n=48); and all Tanzanian health staff in charge of
      preventive health (n=17). Additional information was also collected through focus
      group discussions. RESULTS: HIT refugees used their own health initiatives, which
      resulted in a growth of self-confidence. There was an evidence of benefits,
      especially in promoting health education, affirmed by an almost established
      consensus among the refugee community, Tanzanian health staff and HIT members
      themselves. However, refugee community members who did not know any HIT members
      had less positive health-seeking behaviours than those who knew one or more HIT
      members, thus showing a need for further dissemination of HIT services.
      CONCLUSIONS: Participation in the health services led the HIT refugees to regain
      the sense that they could contribute to solving peers' health problems with their
      own knowledge and services, and by working together as a team. Beneficiary
      participation is a dynamic process that heightened responsibility and health
      consciousness, along with a concomitant gain in power over their destiny.

PMID- 14643628
TI  - Risk factors for overall and persistent diarrhoea in infancy in Antalya, Turkey:
      a cohort study.
AB  - The aim of this study was to identify factors that influence the incidence of
      diarrhoea in infancy. The study was a prospective cohort study conducted in two
      primary healthcare unit areas in Antalya, Turkey. A total of 204 infants were
      followed until they were aged 1 year. Morbidity surveillance and anthropometric
      measurements were carried out by home visits every 2 months. The average
      incidences were found to be 2.76 episodes per child-year for overall diarrhoea
      and 18.56 episodes per 100 child-years for persistent diarrhoea. Relative risks,
      confidence intervals and logistic regression analyses were used to assess the
      associations. For both overall diarrhoea and persistent episodes, increased risks
      were associated with having an uneducated mother (RR=1.89 and 5.33, respectively)
      and a self-employed father (RR=1.89 and 3.77, respectively). Among environmental
      factors, living in a slum was associated with both overall (RR=1.68) and
      persistent (RR=2.69) diarrhoea, whereas living in a crowded house (RR=1.70),
      having no kitchen (RR=2.27) or having an unhygienic toilet (RR=1.93) were found
      to be significant for overall episodes alone. Factors related to the infant were
      preterm birth (RR=1.64), low birth weight (RR=2.05), and first breastfeed given
      more than 1 h after birth (RR=1.64). Nutritional status was also associated with
      overall or persistent diarrhoea: underweight children (RR=2.15, persistent
      diarrhoea only), stunted children (RR=1.67 and 2.14, respectively) or wasted
      children (RR=1.54 and 3.20, respectively). By logistic regression analysis, both
      overall and persistent diarrhoea were found to be associated with mother's
      education.

PMID- 14643629
TI  - Demand-based water options for arsenic mitigation: an experience from rural
      Bangladesh.
AB  - A supply of safe drinking water is a recognized global concern. The arsenic
      contamination of groundwater in Bangladesh and other countries has furthered this
      concern. Lack of appropriate water options is one of the main barriers to the
      supply of safe drinking water for 30-60 million people who are exposed to the
      risk of drinking arsenic-contaminated water in Bangladesh. This paper describes
      the experience from a water supply programme for arsenic mitigation based on
      demand and participation of 30,000 rural people in Srinagar, a subdistrict of
      Bangladesh. About 85% of the 912 tubewell water samples tested had an arsenic
      content higher than 0.05 mg/l. The project promoted 11 options including
      groundwater, surface-water and rainwater-harvesting household-based options as
      well as community managed technologies. Most people, particularly women, wanted
      piped water, and hand-operated deep tubewells were also requested. Four cluster
      based motorized piped water systems, 20 home-based arsenic-removal options (two
      types) and an arsenic-removal filter plant were installed. The public contributed
      about 49, 25 and 20% of the installation costs of piped water, home-based options
      and filter options, respectively, and 100% of all operation and maintenance
      costs. The household options and filter plant were abandoned within a few weeks.
      Reportedly, those options required too much attention, discharged small volumes
      of water at low rates, were difficult to maintain, and discharged poor-quality
      water. The proportion of families (54%) that drank arsenic-contaminated water
      during the final survey was significantly lower than in the baseline survey
      (87%). For arsenic-affected areas, it is recommended that a cluster-based piped
      water system be given proper consideration when selecting appropriate water
      options rather than household-based options or the development of new low-cost
      options.

PMID- 14643630
TI  - You are what you eat: salt consumption and hypertension.

PMID- 14643634
TI  - Role of fusion protein cleavage site in the virulence of Newcastle disease virus.
AB  - Newcastle disease virus (NDV) causes a highly contagious and economically
      important disease in poultry. Viral determinants of NDV virulence are not
      completely understood. The amino acid sequence at the protease cleavage site of
      the fusion (F) protein has been postulated as a major determinant of NDV
      virulence. In this study, we have examined the role of F protein cleavage site
      sequence in NDV virulence using reverse genetics technology. The sequence G-R-Q-G
      R present at the cleavage site of the F protein of avirulent strain LaSota was
      mutated to R-R-Q-K-R, which is present in the F cleavage site of neurovirulent
      strain Beaudette C (BC). The resultant mutated LaSota V.F. virus did not require
      exogenous protease for infectivity in cell culture, indicating that the F protein
      was cleaved by intracellular proteases. The virulence of the mutant and parental
      viruses was evaluated in vivo by intracerebral pathogenicity index (ICPI) and
      intravenous pathogenicity index (IVPI) tests in chickens. Our results showed that
      the modification of the F protein cleavage site resulted in a dramatic increase
      in virulence from an ICPI value of 0.00 for LaSota to a value of 1.12 for LaSota
      V.F. However, the ICPI value of LaSota V.F. was lower than that of BC, which had
      a value of 1.58. Interestingly, the IVPI tests showed values of 0.00 for both
      LaSota and LaSota V.F. viruses, compared to the IVPI value of 1.45 of BC. In
      vitro characteristics of the viruses were also studied. Our results demonstrate
      that the efficiency of cleavage of the F protein plays an important role if the
      NDV is delivered directly into the brains of chicks, but there could be other
      viral factors that probably affect peripheral replication, viremia, or entry into
      the central nervous system.

PMID- 14643635
TI  - Mycobacterium bovis infection of vitamin D-deficient NOS2-/- mice.
AB  - Vitamin D deficiency is associated with an increased risk for tuberculosis
      infection. Studies using in vitro systems indicate that 1,25-dihydroxyvitamin
      D(3) [i.e. 1,25(OH)(2)D(3)], the most active form of the vitamin, enhances
      mycobacterial killing by increasing nitric oxide (NO) production. To evaluate
      concurrently the role of 1,25(OH)(2)D(3) and NO on the host response to
      tuberculosis infection, mice deficient in NO synthase 2 (NOS2(-/-)) and/or
      vitamin D were aerosol-challenged with Mycobacterium bovis and subsequently
      evaluated for mycobacterial colonization and lesion formation. Infected NOS2(-/-)
      mice developed severe necrotizing pyogranulomatous inflammation of the lungs with
      heavy M. bovis colonization and systemic dissemination of the bacillus.
      Colonization and lung lesion area of NOS2(-/-) mice exceeded that of NOS2(+/+)
      mice. Additionally, disease progression was more rapid in NOS2(-/-) mice than in
      NOS2(+/+) mice. Lung colonization and lesion area of vitamin D deficient mice
      exceeded that of vitamin D replete mice, regardless of NOS2 phenotype. However,
      effects of vitamin D on colonization, but not lesion area, were more pronounced
      in NOS2(+/+) mice than in NOS2(-/-) mice. These findings are consistent with the
      current hypothesis that 1,25(OH)(2)D(3) enhances mycobacterial killing through a
      NO-dependent mechanism. As responses of NOS2(-/-) mice were affected by
      1,25(OH)(2)D(3) deficiency, albeit to a lesser extent than were those of
      NOS2(+/+) mice, NO-independent actions of 1,25(OH)(2)D(3) also likely exist.

PMID- 14643636
TI  - RpoS and RpoN are involved in the growth-dependent regulation of rfaH
      transcription and O antigen expression in Salmonella enterica serovar Typhi.
AB  - We reported earlier that the production of O antigen lipopolysaccharide (LPS) by
      Salmonella enterica serovar Typhi (Salmonella typhi) increases at the onset of
      stationary phase and correlates with a growth-regulated expression of the rfaH
      gene under the control of the alternative sigma factor RpoN (Microbiology 148
      (2002) 3789). In this study, we demonstrate that RpoS also modulates rfaH
      promoter activity as revealed by the absence of growth-dependent regulation of an
      rfaH-lacZ transcriptional fusion and O antigen production in a S. typhi rpoS
      mutant. Introduction of a constitutively expressed rpoN gene into the rpoS mutant
      restored increased production of O antigen during stationary phase, suggesting
      that constitutive production of RpoN could overcome the RpoS defect. Similar
      results were observed when an rpoS rpoN double mutant was transformed with the
      intact rpoN gene. Thus, we conclude that both RpoS and RpoN control the rfaH
      promoter activity and concomitantly, the production of O-specific LPS in S.
      typhi.

PMID- 14643637
TI  - Reduced severity of middle ear infection caused by nontypeable Haemophilus
      influenzae lacking the hemoglobin/hemoglobin-haptoglobin binding proteins (Hgp)
      in a chinchilla model of otitis media.
AB  - Since Haemophilus influenzae lacks enzymes necessary for synthesis of the
      porphyrin ring, it has an absolute growth requirement for a porphyrin source.
      This requirement can be satisfied in vitro by hemoglobin and hemoglobin complexed
      to haptoglobin. The products of the hgp genes mediate the utilization of heme
      from hemoglobin-haptoglobin. These genes are also involved in the use of heme
      from hemoglobin, although additional gene products independently mediate the
      acquisition of heme from this substrate. Different strains of H. influenzae
      possess one to four hgp genes. A nontypeable H. influenzae mutant lacking all the
      hgp genes was constructed and compared to the wild-type strain in a chinchilla
      (Chinchilla lanigera) model of otitis media. Compared to the wild-type strain,
      the hgp-deficient mutant exhibited a significantly delayed onset of detectable
      middle ear infection and significantly reduced duration of infection as assessed
      by both video otoscopy and tympanometry and as evidenced by viable bacterial
      counts in middle ear effusions. In addition, the maximum bacterial load in the
      middle ears of chinchillas infected with the mutant strain was significantly
      reduced when compared to the parent. These data indicate that the
      hemoglobin/hemoglobin-haptoglobin binding proteins are required for bacterial
      proliferation during H. influenzae-induced otitis media in chinchillas.

PMID- 14643638
TI  - Differential expression of three Chlamydia trachomatis hsp60-encoding genes in
      active vs. persistent infections.
AB  - Real time RT-PCR was used to assess expression of the three Chlamydia trachomatis
      hsp60-encoding genes (Ct110, Ct604, Ct755) over time in in vitro systems of
      active vs. persistent infection, and in synovial samples from patients with
      Chlamydia-induced arthritis. In HEp-2 cells actively infected with C. trachomatis
      (serovar K), mRNA from Ct110 (groEL) was apparent by 8 h post-infection (p.i.)
      and increased more than 10-fold through 48 h p.i.; mRNA from Ct604 followed a
      similar pattern. Transcripts from Ct755 were abundant at 8 h p.i. and remained 2
      3-fold higher than those from Ct110 at all times. In persistently infected human
      monocytes in culture, expression of Ct110 and Ct755 was low from 1 to 7d p.i.,
      while mRNA from Ct604 was abundant at 1d p.i. and increased more than 3-fold from
      1 to 3d p.i., as the organism transited to the persistent state. Those mRNA
      levels remained high through 7d p.i. Real time analyses of RNA/cDNA from synovial
      tissue of patients with Chlamydia-associated arthritis showed high Ct604 mRNA
      levels, consistent with results from the in vitro monocyte system of persistence.
      These data demonstrate that each chlamydial hsp60-encoding gene is expressed
      independently, and that the three genes are expressed differentially in active
      vs. persistent infection. The results further suggest that the Ct604 gene product
      may function importantly during chlamydial persistence.

PMID- 14643639
TI  - IFN-gamma induced persistent Chlamydia pneumoniae infection in HL and Mono Mac 6
      cells: characterization by real-time quantitative PCR and culture.
AB  - Growth of Chlamydia pneumoniae during gamma interferon (IFN-gamma) induced
      persistent infection in epithelial (HL) and monocyte-macrophage (Mono Mac 6) cell
      lines was studied by a quantitative real-time PCR and passage. When HL cultures
      were treated with IFN-gamma (25 U/ml), the replication of C. pneumoniae DNA was
      unaffected while differentiation into infectious elementary bodies (EB) was
      strongly inhibited, and in contrast to the untreated cultures, no second cycle of
      infection was observed. The estimated doubling time of C. pneumoniae genomes was
      6-7 h in both IFN-gamma treated and untreated HL cultures. At 72 h post
      inoculation, most infectious EBs were released from untreated cultures, whereas
      in IFN-gamma treated HL cells >90% of C. pneumoniae genomes were in non
      infectious form. A higher dose (1000 U/ml) of IFN-gamma was needed to restrict
      growth of C. pneumoniae in Mono Mac 6 cells. In untreated Mono Mac 6 cultures,
      the growth curve of C. pneumoniae resembled that observed in HL cells, except
      that no second cycle of infection could be detected. In IFN-gamma treated Mono
      Mac 6 cultures, the number of infectious C. pneumoniae EBs recovered decreased
      gradually after 3 days post inoculation, while C. pneumoniae genome load remained
      unaltered suggesting persistence of C. pneumoniae also in these cells.

PMID- 14643640
TI  - Chemokine and cytokine production during Orientia tsutsugamushi infection in
      mice.
AB  - Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative
      agent of scrub typhus which is histopathologically characterized by inflammatory
      manifestations, indicating that rickettsiae induce mechanisms that amplify the
      inflammatory response. To understand the pathogenesis of scrub typhus, we
      examined chemokine and cytokine production after infection with O. tsutsugamushi
      in mice. The mRNAs that were upregulated included lymphotactin, RANTES (regulated
      upon activation, normal T-cell expressed and secreted), macrophage inflammatory
      proteins 1alpha/beta (MIP-1alpha/beta), MIP-2, monocyte chemoattractant protein
      1, lymphotoxin beta, tumor necrosis factor alpha, interleukin-6, gamma
      interferon, transforming growth factor beta1, and migration inhibition factor.
      Peak expression of these chemokines and cytokines was observed between 4 and 8
      days after infection. Gene induction was followed by the secretion of chemokine
      and cytokine proteins. Chemokine profile in infected mice was well correlated
      with kinetics of inflammatory cell infiltration. Thus, O. tsutsugamushi appears
      to be a strong inducer of chemokines and cytokines which may, by the attraction
      and activation of phagocytic leukocytes, significantly contribute to inflammation
      observed in scrub typhus.

PMID- 14643641
TI  - Size-number trade-off and optimal offspring size for offspring produced
      sequentially using a fixed amount of reserves.
AB  - We analysed the nature of size-number trade-off of offspring when multiple
      cohorts of such offspring are produced sequentially using a fixed amount of
      reserves. In the model, we incorporated sink-limitation in the resource
      absorption rate of offspring from the mother tissue and the loss of resources by
      maintenance respiration. We found that the later the initiation of a cohort, the
      greater the cost of producing a cohort with the same size and number of
      offspring. This is due to the loss of resources by maintenance respiration during
      the period from the beginning of reproduction to the initiation of the cohort.
      Also, the extra cost increases with an increase in the specific maintenance
      respiration rate. Thus, resources lost to respiration over time reduces the
      fitness value of producing late cohorts. Hence, it is advantageous to produce all
      offspring simultaneously unless there are fitness advantages of producing
      offspring sequential which overcome this cost or constraints preventing
      simultaneous production. Sequentially offspring production evolves if there is a
      constraint on the number of offspring of each cohort. With this constraint, the
      optimal offspring size decreases with the production sequence of cohorts.

PMID- 14643642
TI  - Integration of kinetic information on yeast sphingolipid metabolism in dynamical
      pathway models.
AB  - For the first time, kinetic information from the literature was collected and
      used to construct integrative dynamical mathematical models of sphingolipid
      metabolism. One model was designed primarily with kinetic equations in the
      tradition of Michaelis and Menten whereas the other two models were designed as
      alternative power-law models within the framework of Biochemical Systems Theory.
      Each model contains about 50 variables, about a quarter of which are dependent
      (state) variables, while the others are independent inputs and enzyme activities
      that are considered constant. The models account for known regulatory signals
      that exert control over the pathway. Standard mathematical testing, repeated
      revisiting of the literature, and numerous rounds of amendments and refinements
      resulted in models that are stable and rather insensitive to perturbations in
      inputs or parameter values. The models also appear to be compatible with the
      modest amount of experimental experience that lends itself to direct comparisons.
      Even though the three models are based on different mathematical representations,
      they show dynamic responses to a variety of perturbations and changes in
      conditions that are essentially equivalent for small perturbations and similar
      for large perturbations. The kinetic information used for model construction and
      the models themselves can serve as a starting point for future analyses and
      refinements.

PMID- 14643643
TI  - Evolution of cannibalism: referring to costs of cannibalism.
AB  - A rational explanation for cannibalism is that it would be favored under
      conditions of crowding of conspecific individuals and/or low availability of
      alternative prey with the fear of starvation, so as to maximize individual
      fitness. Cannibalism has, however, not evolved and is not maintained by a simple
      individual optimization, while it has evolved and is maintained as a game among
      population members. We analysed the attainable state of an evolutionary
      cannibalism game within a framework that reflects the minimum essence of cause
      effect in the cannibalism phenomenon. Cannibalism is predator-prey interaction
      among conspecifics. Immediate direct payoffs (survival in the interaction among
      conspecifics) and indirect payoffs (growth results in potential productivity and
      survival against the threat of starvation) would be included. No morphological
      specialization and no size priority of cannibalism individuals are assumed as
      conservative situations in which we analyse the possibility of cannibalism.
      Cannibalism would be possible under the conservative condition, if initially the
      wild population's cannibalism rate is not sufficiently lower than a threshold
      value. Crowding and/or low availability of alternative prey with the fear of
      starvation facilitates cannibalism evolution. Energy gain from conspecific prey
      would be attenuated by costs of counterattacks by conspecific victims and by
      challenge cost of its own. Discounting net intake energy required in the arms
      race for cannibalism challenge result in a relative disadvantage of having a high
      cannibalism rate and makes an evolutionary equilibrium of low cannibalism rate,
      even when potential profitability of conspecific prey is high.

PMID- 14643644
TI  - The total quasi-steady-state approximation is valid for reversible enzyme
      kinetics.
AB  - The Briggs-Haldane approximation of the irreversible Michaelis-Menten scheme of
      enzyme kinetics is cited in virtually every biochemistry textbook and is widely
      considered the classic example of a quasi-steady-state approximation. Though of
      similar importance, the reversible Michaelis-Menten scheme is not as well
      characterized. This is a serious limitation since even enzymatic reactions that
      go to completion may be reversible. The current work derives a total quasi-steady
      state approximation (tQSSA) for the reversible Michaelis-Menten and delineates
      its validity domain. The tQSSA allows the derivation of uniformly valid
      approximations for the limit of low enzyme concentrations, ET<<ST+KM, and under
      certain more restrictive conditions also for high enzyme concentrations such that
      ST<<ET+KM. Using these simple analytical approximations, a sequential
      experimental-theoretical method is suggested for unambiguously estimating all the
      kinetic parameters of the reversible Michaelis-Menten scheme.

PMID- 14643645
TI  - Effect of selection on the topology of genealogical trees.
AB  - Selection is one of the factors that most influence the shape of genealogical
      trees. Here we report results of simulations of the infinite-sites version of
      Moran's model of population genetics aiming at quantifying how the presence of
      selection affects the branching pattern (topology) of binary genealogical trees.
      In particular, we consider a scenario of purifying or negative selection in which
      all mutations are deleterious and each new mutation reduces the fitness of the
      individual by the same fraction. Analysis of five statistical measures of tree
      balance or symmetry borrowed from taxonomy indicates that the genealogical trees
      of samples of populations in which selection is actuating are in the average more
      asymmetric than neutral trees and that this effect is enhanced by increasing the
      sample size. However, a quantitative evaluation of the power of these balance
      measures to detect a tree topology significantly distinct from the neutral one
      indicates that they are not useful as tests of neutrality of mutations.

PMID- 14643646
TI  - A model of neutralization of Chlamydia trachomatis based on antibody and host
      cell aggregation on the elementary body surface.
AB  - Humoral immunity is that aspect of specific immunity that is mediated by B
      lymphocytes and involves the neutralizing of pathogens by means of antibodies
      attaching to the pathogen's binding sites. Antibodies bind to and block ligand
      sites on the pathogen which prevents these sites from attaching to target cell
      receptors and so cell entry is inhibited. Many studies investigate the role of
      humoral immunity for protection against chlamydial challenge and they have shown
      that neutralization of the chlamydial body requires a large number of attached
      antibodies. Steric hindrance greatly influences the number of available sites
      that may be bound, reducing relative occupancy well below 100%. We model steric
      effects of antibody Fab fragment attachment indicating that they must be taken
      into consideration to accurately model valency, the number of available binding
      sites. We derive a partial differential equation for the number of antibody Fabs
      and host cell receptors that are aggregated to extracellular chlamydial
      elementary bodies. We consider steric effects in describing the size distribution
      of aggregates. Our theory is in good agreement with Monte Carlo simulations of
      binding. We use our theoretical prediction for the valency in a model for the in
      host population dynamics of a chlamydial infection and we fit our model to
      experimental data.

PMID- 14643647
TI  - Optimization modeling of plant root architecture for water and phosphorus
      acquisition.
AB  - An optimization model is presented that examines the relationship between root
      architecture and multiple resource acquisition, specifically water and phosphorus
      in spatially heterogeneous environments. The basal root growth angle of an
      individual common bean plant, which determines the orientation and localization
      of the bulk of the root system, was modeled as the decision variable. The total
      payoff to the plant, the benefit obtained from water and phosphorus acquisition,
      minus the costs of spatial competition between roots, is given as a function of
      the (x,y) coordinates of the basal root in two-dimensional Cartesian space. We
      obtained a general solution and applied it to four unique environmental cases
      which are as follows: (1) the case of uniformly distributed water and phosphorus;
      (2) the case of localized shallow phosphorus; (3) the case of localized deep
      water; and (4) the case of shallow phosphorus and deep water. The general
      solution states that the optimal basal root growth angle will occur at the point
      where the total rate of change in the value of the resources acquired equals the
      total rate of change in cost that results from locating the root deeper in the
      soil. An optimizing plant locates its roots deeper in the soil profile until the
      marginal benefit exactly equals the marginal cost. The model predicts that the
      basal root angle of an optimizing plant will be shallower for Case 2 and deeper
      for Case 3, relative to the basal root angle obtained in the case of uniformly
      distributed water and phosphorus. The optimal basal root angle for Case 4 will
      depend on the marginal rate of substitution of water availability for phosphorus
      availability that occurs with depth. Empirical observations of bean root
      architecture in the greenhouse and in the field confirm model results and are
      discussed. In addition, the potential importance of phenotypic plasticity and
      phenotypic variation are discussed in relation to optimization of traits and
      adaptation to spatially heterogeneous environments.

PMID- 14643648
TI  - Chaos game representation of protein sequences based on the detailed HP model and
      their multifractal and correlation analyses.
AB  - Similar to the chaos game representation (CGR) of DNA sequences proposed by
      Jeffrey (Nucleic Acid Res. 18 (1990) 2163), a new CGR of protein sequences based
      on the detailed HP model is proposed. Multifractal and correlation analyses of
      the measures based on the CGR of protein sequences from complete genomes are
      performed. The Dq spectra of all organisms studied are multifractal-like and
      sufficiently smooth for the Cq curves to be meaningful. The Cq curves of bacteria
      resemble a classical phase transition at a critical point. The correlation
      distance of the difference between the measure based on the CGR of protein
      sequences and its fractal background is also proposed to construct a more precise
      phylogenetic tree of bacteria.

PMID- 14643649
TI  - The relative importance of herbivory and carnivory on the distribution of energy
      in a stochastic tri-trophic food web.
AB  - A three-state, discrete-time Markov chain is used to model the dynamics of energy
      flow in a tri-trophic food web. The distribution of energy in the three trophic
      levels is related to the rates of flow between the trophic levels and calculated
      for the entire range of possible flow values. These distributions are then
      analysed for stability and used to test the idea that plants are resource-limited
      and herbivores are predation-limited. Low rates of death and decomposition, when
      coupled with low rates of herbivory and carnivory, tend to destabilize this food
      web. Food webs with higher rates of death and decomposition are relatively more
      stable regardless of rates of herbivory and carnivory. Plants are more prone to
      resource-limitation and herbivores are, in general, limited by their predators,
      which supports Hairston et al. (Am. Nat. 94 (1960) 421). The rate of
      decomposition often mediates the roles of top-down and bottom-up control of
      energy flow in the food web.

PMID- 14643650
TI  - A quantitative description of the diffusion of noradrenaline in the media of
      blood vessels following its release from sympathetic varicosities.
AB  - A quantitative model is provided which describes how noradrenaline (NAd),
      released from varicosities at the adventitial surface of an artery, either
      diffuses into the media of the vessel to reach the intimal surface, diffuses into
      the volume of solution surrounding the artery, or is removed by the uptake 1
      process in the varicosities. These predictions are then compared with
      experimental evaluations of the extent of changes in NAd to be found at the
      adventitial and intimal surfaces of the rat-tail artery, during and after trains
      of impulses, as determined using amperometry. In the model of the blood vessel
      there is a sequential decrease in the diffusion constant of NAd from the
      surrounding solution, to the adventitia, to the media, to the endothelium, to
      rise again in the lumen of the vessel; there is also an uptake 1 NAd pump in the
      varicosities described by Michaelis-Menten kinetics. This model is shown to
      provide a quantitative account of the spatial and temporal changes in NAd
      observed following trains of impulses at different frequencies of stimulation (5
      40 Hz) for different periods of times (10-40 s). Changes in the spatio-temporal
      distribution of NAd observed following block of the uptake 1 NAd pump were also
      successfully predicted by the model. It is concluded that, within the context of
      the model, there is no need to evoke special mechanisms of buffering at the
      sympathetic varicosities, nor distinctions on the basis that only secreting
      varicosities utilize the uptake 1 mechanism, in order to describe the dynamics of
      NAd distribution in arteries during nerve activity.

PMID- 14643651
TI  - The crystal structure of the carbohydrate-recognition domain of the glycoprotein
      sorting receptor p58/ERGIC-53 reveals an unpredicted metal-binding site and
      conformational changes associated with calcium ion binding.
AB  - p58/ERGIC-53 is a calcium-dependent animal lectin that acts as a cargo receptor,
      binding to a set of glycoproteins in the endoplasmic reticulum (ER) and
      transporting them to the Golgi complex. It is similar in structure to calcium
      dependent leguminous lectins. We have determined the structure of the
      carbohydrate-recognition domain of p58/ERGIC-53 in its calcium-bound form. The
      structure reveals localized but large conformational changes in relation to the
      previously determined metal ion-free structure, mapping mostly to the ligand
      binding site. It reveals the presence of two calcium ion-binding sites located 6A
      apart, one of which has no equivalent in the plant lectins. The second metal ion
      binding site present in that class of lectins, binding Mn(2+), is absent from
      p58/ERGIC-53. The absence of a short loop in the ligand-binding site in this
      protein suggests that it has adapted to optimally bind the high-mannose
      Man(8)(GlcNAc)(2) glycan common to glycoproteins at the ER exit stage.

PMID- 14643652
TI  - Crystal structure of the human liver X receptor beta ligand-binding domain in
      complex with a synthetic agonist.
AB  - LXRbeta belongs to the nuclear hormone receptor superfamily of ligand-activated
      transcription factors. Its natural ligands are supposed to be oxidised
      derivatives of cholesterol. Stimulation of LXRbeta by agonists activates a number
      of genes that are involved in the regulation of lipid metabolism and cholesterol
      efflux from cells. Therefore, LXRbeta may represent a novel therapeutic target
      for the treatment of dyslipidemia and atherosclerosis.Here, we report the X-ray
      crystal structure of the LXRbeta ligand-binding domain in complex with a
      synthetic agonist, T-0901317. This compound occupies the ligand-binding pocket of
      the receptor, forms numerous lipophilic contacts with the protein and one crucial
      hydrogen bond to His435 and stabilises the agonist conformation of the receptor
      ligand-binding domain. The recruitment of the AF2-region of the protein is not
      achieved via direct polar interactions of the ligand with protein side-chains of
      this helical segment, but rather via few hydrophobic contacts and probably more
      importantly via indirect effects involving the pre-orientation of side-chains
      that surround the ligand-binding pocket and form the interface to the AF2-helix.
      On the basis of these results we propose a binding mode and a mechanism of action
      for the putative natural ligands, oxidised derivatives of cholesterol.

PMID- 14643653
TI  - Interaction of the repressor element 1-silencing transcription factor (REST) with
      target genes.
AB  - The repressor element 1-silencing transcription factor (REST) has been proposed
      to restrict expression of repressor element 1 (RE1) bearing genes to
      differentiated neurons by silencing their expression in non-neural tissue. Here,
      we have examined the interaction of REST with the M(4) muscarinic acetylcholine
      receptor gene. We show that REST binds to the RE1 of the M(4) gene in those cell
      lines and brain regions where the M(4) gene is expressed but not in those where
      the M(4) is not expressed. Furthermore, in cells that express M(4), the presence
      of REST represses but is insufficient to silence transcription of M(4). In non
      neural cells REST is absent from the RE1 of the silent M(4) gene and perturbation
      of REST function fails to induce M(4) expression. We propose that REST acts to
      regulate expression levels of some RE1-bearing genes in neural cells, thereby
      playing an important role in defining neuronal activity.

PMID- 14643654
TI  - Separate and coordinate transcriptional control mechanisms link expression of the
      potentially lethal KilB spread locus to the upstream transmission operon on
      Streptomyces plasmid pIJ101.
AB  - Efficient conjugation of the high copy plasmid pIJ101 among members of the
      bacterial genus Streptomyces depends on a single plasmid gene (tra) for initial
      inter-mycelial transfer, and involves three additional pIJ101 functions (spdA,
      spdB, and kilB), which may promote intra-mycelial spread of the plasmid upon its
      entrance into the recipient. The genes tra, spdA, and spdB are co-transcribed as
      part of an operon, whose expression is negatively controlled by the pIJ101
      repressor KorA. Downstream of this transmission operon and in the same
      orientation, the kilB spread gene possesses its own promoter, which is recognized
      by the pIJ101 KorB repressor protein; binding of KorB appears to prevent the
      lethal overexpression of the KilB protein, which otherwise shows a temporally
      increasing pattern of production or accumulation during the streptomycete life
      cycle. To define better the mechanism(s) controlling the concentration of the
      potentially toxic KilB protein in cells, a variety of transcriptional analyses
      involving the kilB promoter and kilB-specific mRNA were performed. These studies
      demonstrated that transcription originating from the kilB promoter on pIJ101 is
      dramatically reduced by KorB binding under non-mating conditions; more
      significantly, however, as judged by evidence of readthrough transcription across
      the kilB promoter region and polarity effects of upstream insertion and deletion
      mutations, kilB was found to be expressed also as part of the transmission operon
      with optimal KilB production being necessarily tied to such co-transcription. Our
      data indicate that the genes tra, spdA, spdB, and kilB comprise an unusual operon
      in which separate tight control of the distal gene (kilB) by the KorB repressor
      is superimposed on coordinate regulation of full operon transcription by KorA.
      Moreover, our results imply that potential interactions between elongating RNA
      polymerase molecules synthesizing transmission operon transcripts and KorB
      repressor bound to the intercistronic kilB promoter region are important for
      modulating kilB expression.

PMID- 14643655
TI  - The refined structure of a protein catenane: the HK97 bacteriophage capsid at
      3.44 A resolution.
AB  - The HK97 bacteriophage capsid is a unique example of macromolecular catenanes:
      interlocked rings of covalently attached protein subunits. The chain mail
      organization of the subunits stabilizes a particle in which the maximum thickness
      of the protein shell is 18A and the maximum diameter is 550A. The electron
      density has the appearance of a balloon illustrating the extraordinary strength
      conferred by the unique subunit organization. The refined structure shows novel
      qualities of the HK97 shell protein, gp5 that, together with the protease gp4,
      guides the assembly and maturation of the virion. Although gp5 forms hexamers and
      pentamers and the subunits exist in different structural environments, the
      tertiary structures of the seven protein molecules in the viral asymmetric unit
      are closely similar. The interactions of the subunits in the shell are
      exceptionally complex with each subunit interacting with nine other subunits. The
      interactions of the N-terminus released after gp5 cleavage appear important for
      organization of the loops that become crosslinked to the core of a neighboring
      subunit at the maturation. A comparison with a model of the Prohead II structure
      revealed that the surfaces of non-covalent contact between the monomers that
      build up hexamers/pentamers are completely redefined during maturation.

PMID- 14643656
TI  - Naturally-occurring modification restricts the anticodon domain conformational
      space of tRNA(Phe).
AB  - Post-transcriptional modifications contribute chemistry and structure to RNAs.
      Modifications of tRNA at nucleoside 37, 3'-adjacent to the anticodon, are
      particularly interesting because they facilitate codon recognition and negate
      translational frame-shifting. To assess if the functional contribution of a
      position 37-modified nucleoside defines a specific structure or restricts
      conformational flexibility, structures of the yeast tRNA(Phe) anticodon stem and
      loop (ASL(Phe)) with naturally occurring modified nucleosides differing only at
      position 37, ASL(Phe)-(Cm(32),Gm(34),m(5)C(40)), and ASL(Phe)
      (Cm(32),Gm(34),m(1)G(37),m(5)C(40)), were determined by NMR spectroscopy and
      restrained molecular dynamics. The ASL structures had similarly resolved stems
      (RMSD approximately 0.6A) of five canonical base-pairs in standard A-form RNA.
      The "NOE walk" was evident on the 5' and 3' sides of the stems of both RNAs, and
      extended to the adjacent loop nucleosides. The NOESY cross-peaks involving U(33)
      H2' and characteristic of tRNA's anticodon domain U-turn were present but weak,
      whereas those involving the U(33) H1' proton were absent from the spectra of both
      ASLs. However, ASL(Phe)-(Cm(32),Gm(34),m(1)G(37),m(5)C(40)) exhibited the
      downfield shifted 31P resonance of U(33)pGm(34) indicative of U-turns; ASL(Phe)
      (Cm(32),Gm(34),m(5)C(40)) did not. An unusual "backwards" NOE between Gm(34) and
      A(35) (Gm(34)/H8 to A(35)/H1') was observed in both molecules. The RNAs exhibited
      a protonated A(+)(38) resulting in the final structures having C(32).A(+)(38)
      intra-loop base-pairs, with that of ASL(Phe)-(Cm(32),Gm(34),m(1)G(37),m(5)C(40))
      being especially well defined. A single family of low-energy structures of
      ASL(Phe)-(Cm(32),Gm(34), m(1)G(37),m(5)C(40)) (loop RMSD 0.98A) exhibited a
      significantly restricted conformational space for the anticodon loop in
      comparison to that of ASL(Phe)-(Cm(32),Gm(34),m(5)C(40)) (loop RMSD 2.58A). In
      addition, the ASL(Phe)-(Cm(32),Gm(34),m(1)G(37),m(5)C(40)) average structure had
      a greater degree of similarity to that of the yeast tRNA(Phe) crystal structure.
      A comparison of the resulting structures indicates that modification of position
      37 affects the accuracy of decoding and the maintenance of the mRNA reading frame
      by restricting anticodon loop conformational space.

PMID- 14643657
TI  - Eclipse-synchrony relationship in Escherichia coli strains with mutations
      affecting sequestration, initiation of replication and superhelicity of the
      bacterial chromosome.
AB  - Initiation of replication from oriC on the Escherichia coli chromosomes occurs
      once and only once per generation at the same cell mass per origin. During rapid
      growth there are overlapping replication cycles, and initiation occurs
      synchronously at two or more copies of oriC. Since the bacterial growth can vary
      over a wide range (from three divisions per hour to 2.5 hours or more per
      division) the frequency of initiation should change in coordination with
      bacterial growth. Prevention of reinitiation from a newly replicated origin by
      temporary sequestration of the hemi-methylated GATC-sites in the origin region
      provides the molecular/genetic basis for the maintenance of the eclipse period
      between two successive rounds of replication. Sequestration is also believed to
      be responsible for initiation synchrony, since inactivation of either the seqA or
      the dam gene abolishes synchrony while drastically reducing the eclipse. In this
      work, we attempted to examine the functional relationship(s) between the eclipse
      period and the synchrony of initiation in E.coli strains by direct measurements
      of these parameters by density-shift centrifugation and flow-cytometric analyses,
      respectively. The eclipse period, measured as a fraction of DNA-duplication
      times, varied continuously from 0.6 for the wild-type E.coli K12 to 0.1 for
      strains with mutations in seqA, dam, dnaA, topA and gyr genes (all of which have
      been shown to cause asynchrony) and their various combinations. The asynchrony
      index, a quantitative indicator for the loss of synchrony of initiation, changed
      from low (synchronous) to high (asynchronous) values in a step-function-like
      relationship with the eclipse. An eclipse period of approximately 0.5 generation
      time appeared to be the critical value for the switch from synchronous to
      asynchronous initiation.

PMID- 14643658
TI  - DNA binding specificity of the replication initiator protein, DnaA from
      Helicobacter pylori.
AB  - The key protein in the initiation of Helicobacter pylori chromosome replication,
      DnaA, has been characterized. The amount of the DnaA protein was estimated to be
      approximately 3000 molecules per single cell; a large part of the protein was
      found in the inner membrane. The H.pylori DnaA protein has been analysed using in
      vitro (gel retardation assay and surface plasmon resonance (SPR)) as well as in
      silico (comparative computer modeling) studies. DnaA binds a single DnaA box as a
      monomer, while binding to the fragment containing several DnaA box motifs, the
      oriC region, leads to the formation of high molecular mass nucleoprotein
      complexes. In comparison with the Escherichia coli DnaA, the H.pylori DnaA
      protein exhibits lower DNA-binding specificity; however, it prefers oriC over non
      box DNA fragments. As determined by gel retardation techniques, the H.pylori DnaA
      binds with a moderate level of affinity to its origin of replication (4nM).
      Comparative computer modelling showed that there are nine residues within the
      binding domain which are possible determinants of the reduced H.pylori DnaA
      specificity. Of these, the most interesting is probably the triad PTL; all three
      residues show significant divergence from the consensus, and Thr398 is the most
      divergent residue of all.

PMID- 14643659
TI  - Formation of a DNA mismatch repair complex mediated by ATP.
AB  - The mismatch repair proteins, MutS and MutL, interact in a DNA mismatch and ATP
      dependent manner to activate downstream events in repair. Here, we assess the
      role of ATP binding and hydrolysis in mismatch recognition by MutS and the
      formation of a ternary complex involving MutS and MutL bound to a mismatched DNA.
      We show that ATP reduces the affinity of MutS for mismatched DNA and that the
      modulation of DNA binding affinity by nucleotide is even more pronounced for MutS
      E694A, a protein that binds ATP but is defective for ATP hydrolysis. Despite the
      ATP hydrolysis defect, E694A, like WT MutS, undergoes rapid, ATP-dependent
      dissociation from a DNA mismatch. Furthermore, MutS E694A retains the ability to
      interact with MutL on mismatched DNA. The recruitment of MutL to a mismatched DNA
      by MutS is also observed for two mutant MutL proteins, E29A, defective for ATP
      hydrolysis, and R266A, defective for DNA binding. These results suggest that ATP
      binding in the absence of hydrolysis is sufficient to trigger formation of a MutS
      sliding clamp. However, recruitment of MutL results in the formation of a dynamic
      ternary complex that we propose is the intermediate that signals subsequent
      repair steps requiring ATP hydrolysis.

PMID- 14643660
TI  - Gene conversion in transposition of Escherichia coli element IS30.
AB  - The mobile element IS30 has dual target specificity, since it can integrate
      adjacent to the inverted repeat (IR) of another IS30 copy or into hot-spot
      sequences characterized by a well-defined consensus showing no similarity to the
      ends of the element. The result of such integrations into these targets is
      different, as gene conversion events take place frequently during insertion next
      to an IR end, while this phenomenon has never been observed in targeting hot-spot
      sequences. Conversion events in IR-targeting cannot be explained exclusively by
      the activity of the transposase, but suggest the involvement of the homologous
      recombination and repair machinery of the host cell. Here, we show that the
      homology between the donor and target sequences is required for conversion and
      the starting point of the process is the site of integration. The frequency of
      conversion depends on the distance of mutations from the end of the targeted
      element. Remarkable bias is found in the role of donor and target DNA, since
      generally the donor sequence is converted depending on the target. Conversion was
      shown to occur also without formation of transposition products. All these data
      are consistent with the idea of the establishment, migration and resolution of a
      Holliday-like cruciform structure, which can be responsible for conversion
      events. To explain the variety of conversion products in IR-targeting, a
      molecular model has been proposed and discussed.

PMID- 14643661
TI  - Comparison of the structure and DNA-binding properties of the E2 proteins from an
      oncogenic and a non-oncogenic human papillomavirus.
AB  - Human papillomaviruses (HPVS) that infect the genital tract can be divided into
      two groups: high-risk HPV types, such as HPV 16 and HPV 18, are associated with
      cancer, low-risk HPV types, such as HPV 6, are associated with benign warts. In
      both high-risk and low-risk HPV types, the papillomavirus E2 protein binds to
      four sites within the viral long control region (LCR) and regulates viral gene
      expression. Here, we present the crystal structure of the minimal DNA-binding
      domain (DBD) from the HPV 6 E2 protein. We show that the HPV 6 E2 DBD is
      structurally more similar to the HPV 18 and bovine papillomavirus type 1 (BPV1)
      E2 proteins than it is to the HPV 16 E2 protein. Using gel retardation assays, we
      show that the hierarchy of E2 sites within the HPV 16 and HPV 6 LCRs are
      different. However, despite these differences in structure and site preference,
      both the HPV 16 and 6 E2 DBDs recognise an extended version of the consensus E2
      binding site derived from studies of the BPV1 E2 protein. In both cases, the
      preferred binding site is 5'AACCGN(4)CGGTT3', where the additional flanking base
      pairs are in bold and N(4) represents a four base-pair central spacer. Both of
      these HPV proteins bind preferentially to E2 sites that contain an A:T-rich
      central spacer. We show that the preference for an A:T-rich central spacer is
      due, at least in part, to the need to adopt a DNA conformation that facilitates
      protein contacts with the flanking base-pairs.

PMID- 14643662
TI  - Assessing the plasticity of DNA target site recognition of the PI-SceI homing
      endonuclease using a bacterial two-hybrid selection system.
AB  - The PI-SceI protein from Saccharomyces cerevisiae is a member of the LAGLIDADG
      family of homing endonucleases that have been used in genomic engineering. To
      assess the flexibility of the PI-SceI-binding interaction and to make progress
      towards the directed evolution of homing endonucleases that cleave specified DNA
      targets, we applied a two-hybrid method to select PI-SceI variants from a
      randomized expression library that bind to different DNA substrates. In
      particular, the codon for Arg94, which is located in the protein splicing domain
      and makes essential contacts to two adjacent base-pairs, and the codons for four
      proximal residues were randomized. There is little conservation of the wild-type
      amino acid residues at the five randomized positions in the variants that were
      selected to bind to the wild-type site, yet one of the purified derivatives
      displays DNA-binding specificity and DNA endonuclease activity that is similar to
      that of the wild-type enzyme. A spectrum of DNA-binding behaviors ranging from
      partial relaxation of specificity to marked shifts in target site recognition are
      present in variants selected to bind to sites containing mutations at the two
      base-pairs. Our results illustrate the inherent plasticity of the PI-SceI/DNA
      interface and demonstrate that selection based on DNA binding is an effective
      means of altering the DNA cleavage specificity of homing endonucleases.
      Furthermore, it is apparent that homing endonuclease target specificity derives,
      in part, from constraints on the flexibility of DNA contacts imposed by hydrogen
      bonds to proximal residues.

PMID- 14643663
TI  - Structure of NFAT bound to DNA as a monomer.
AB  - The nuclear factor of activated T cells (NFAT) is a calcium-dependent
      transcription factor that cooperates with a myriad of partner transcription
      factors to regulate distinct transcription programs. Transcription activation by
      NFAT without the cooperation of co-stimulatory signals in lymphocytes can also
      impose a genetic program of anergy. Although the ternary NFAT1/Fos-Jun/DNA
      complex has been structurally characterized, how NFAT1 recognizes DNA in the
      absence of cooperative partners and how such a binary NFAT/DNA complex may lead
      to the assembly of distinct high-order NFAT transcription complexes are still
      poorly understood. We have determined the crystal structure of the entire Rel
      homology region (RHR) of human NFAT1 (NFATc2) bound to DNA as a monomer. We also
      present footprinting evidence that corroborates the protein-DNA contacts observed
      in the crystal structure. Our structural and biochemical studies reveal the
      mechanism by which the monomeric Rel protein NFAT recognizes its cognate DNA
      site. A remarkable feature of the binary NFAT/DNA complex is the conformational
      flexibility exhibited by NFAT1 in the four independent copies of the NFAT/DNA
      complex in the crystal structure, which may reflect a mechanism by which NFAT1
      interacts with a variety of protein partners as it mediates disparate biological
      responses.

PMID- 14643664
TI  - Closed conformation of the active site loop of rabbit muscle triosephosphate
      isomerase in the absence of substrate: evidence of conformational heterogeneity.
AB  - The active site loop of triosephosphate isomerase (TIM) exhibits a hinged-lid
      motion, alternating between the two well defined "open" and "closed"
      conformations. Until now the closed conformation had only been observed in
      protein complexes with substrate analogues. Here, we present the first rabbit
      muscle apo TIM structure, refined to 1.5A resolution, in which the active site
      loop is either in the open or in the closed conformation in different subunits of
      the enzyme. In the closed conformation described here, the lid loop residues
      participate in stabilizing hydrogen bonds characteristic of holo TIM structures,
      whereas chemical interactions observed in the open loop conformation are similar
      to those found in the apo structures of TIM. In the closed conformation, a number
      of water molecules are observed at the projected ligand atom positions that are
      hydrogen bonded to the active site residues. Additives used during
      crystallization (DMSO and Tris molecules and magnesium atoms) were modeled in the
      electron density maps. However, no specific binding of these molecules is
      observed at, or close to, the active site and the lid loop. To further
      investigate this unusual closed conformation of the apo enzyme, two more rabbit
      muscle TIM structures, one in the same and another in a different crystal form,
      were determined. These structures present the open lid conformation only,
      indicating that the closed conformation cannot be explained by crystal contact
      effects. To rationalize why the active site loop is closed in the absence of
      ligand in one of the subunits, extensive comparison with previously solved TIM
      structures was carried out, supported by the bulk of available experimental
      information about enzyme kinetics and reaction mechanism of TIM. The observation
      of both open and closed lid conformations in TIM crystals might be related to a
      persistent conformational heterogeneity of this protein in solution.

PMID- 14643665
TI  - On the role of structural information in remote homology detection and sequence
      alignment: new methods using hybrid sequence profiles.
AB  - Structural alignments often reveal relationships between proteins that cannot be
      detected using sequence alignment alone. However, profile search methods based
      entirely on structural alignments alone have not been found to be effective in
      finding remote homologs. Here, we explore the role of structural information in
      remote homolog detection and sequence alignment. To this end, we develop a series
      of hybrid multidimensional alignment profiles that combine sequence, secondary
      and tertiary structure information into hybrid profiles. Sequence-based profiles
      are profiles whose position-specific scoring matrix is derived from sequence
      alignment alone; structure-based profiles are those derived from multiple
      structure alignments. We compare pure sequence-based profiles to pure structure
      based profiles, as well as to hybrid profiles that use combined sequence-and
      structure-based profiles, where sequence-based profiles are used in loop/motif
      regions and structural information is used in core structural regions. All of the
      hybrid methods offer significant improvement over simple profile-to-profile
      alignment. We demonstrate that both sequence-based and structure-based profiles
      contribute to remote homology detection and alignment accuracy, and that each
      contains some unique information. We discuss the implications of these results
      for further improvements in amino acid sequence and structural analysis.

PMID- 14643666
TI  - Solution structure of the C-terminal antiparallel coiled-coil domain from
      Escherichia coli osmosensor ProP.
AB  - Bacteria respond to increasing medium osmolality by accumulating organic solutes
      that are compatible with cellular functions. Transporter ProP of Escherichia
      coli, a proton symporter and a member of the major facilitator superfamily,
      senses osmotic shifts and responds by importing osmolytes such as glycine
      betaine. ProP contains a cytoplasmic, C-terminal extension that is essential for
      its activity. A peptide corresponding to the C-terminal extension of ProP forms a
      homodimeric alpha-helical coiled-coil even though some of its heptad a positions
      are not occupied by hydrophobic amino acid residues. Unexpectedly, amino acid
      replacement R488I, occurring at a heptad a position, destabilized the coiled-coil
      formed by the ProP peptide and attenuated the response of the intact transporter
      to osmotic upshifts in vivo. Thus, ProP was proposed to dimerize via an
      antiparallel coiled-coil. We used nuclear magnetic resonance (NMR) spectroscopy
      to determine the structure of the synthetic peptide corresponding to residues 468
      497 of ProP. This region did form an antiparallel coil-coil in which critical
      residue R488 specifies the antiparallel coiled-coil orientation by forming
      stabilizing salt-bridges. Charged residues (both acidic and basic) are clustered
      on the c/g surface of the coiled-coil whereas polar residues are distributed on
      the b/e surface. This causes the structure to be bent, in contrast to other known
      antiparallel coiled-coils (those from the hepatitis delta antigen (PDB ID code
      1A92) and the bovine F(1) ATPase inhibitor protein (PDB ID code 1HF9)). The
      coiled-coil and its possible importance for osmosensing are discussed.

PMID- 14643667
TI  - Origin of unusual phi-values in protein folding: evidence against specific
      nucleation sites.
AB  - phi(f)-value analysis is one of the most common methods to characterize the
      structure of protein folding transition states. It compares the effects of
      mutations on the folding kinetics with the respective effects on equilibrium
      stability. The interpretation of the results usually focuses on a few unusual
      phi(f)-values, which are either particularly high or which are larger than 1 or
      smaller than 0. These mutations are believed to affect the most important regions
      for the folding process. A major uncertainty in experimental phi(f)-values is
      introduced by the commonly used analysis of only a single mutant at various
      positions in a protein (two-point analysis). To test the reliability of two-point
      phi(f)-values we used reference data from three positions in two different
      proteins at which multiple mutations have been introduced. The results show that
      two-point phi(f)-values are highly inaccurate if the difference in stability
      between two variants is less than 7 kJ/mol, corresponding to a 20-fold difference
      in equilibrium constant. Comparison with reported phi(f)-values for 11 proteins
      shows that most unusual phi(f)-values are observed in mutants which show changes
      in protein stability that are too small to allow a reliable analysis. The results
      argue against specific nucleation sites in protein folding and give a picture of
      transition states as distorted native states for the major part of a protein or
      for large substructures.

PMID- 14643668
TI  - The putative helical lid of the Hsp70 peptide-binding domain is required for
      efficient preprotein translocation into mitochondria.
AB  - The mitochondrial Hsp70 (Ssc1) is an essential component of the preprotein import
      machinery, responsible for the unfolding and movement of polypeptide chains
      through the mitochondrial membranes into the matrix. Here, we have analyzed the
      role of the carboxy-terminal variable domain during the protein translocation
      reaction. This segment is thought to form an alpha-helical lid over the substrate
      binding site. Truncated Ssc1 molecules lacking parts or all of the lid region
      showed reduced binding to substrate proteins but were able to interact with the
      co-chaperone Mge1 and the inner membrane anchor Tim44. Deletions of the complete
      lid resulted in a lethal phenotype in vivo, caused by the inability to sustain a
      productive preprotein import function. The translocation defect in vitro was not
      overcome by artificial unfolding of the preprotein prior to the import reaction.
      Despite a reduced substrate affinity, the presence of a minimal lid segment in
      Ssc1 was sufficient to support preprotein import. However, at low reaction
      temperatures or low matrix ATP levels, protein import rates were significantly
      reduced due to an unproductive interaction with the preprotein in transit. We
      conclude that the carboxy-terminal domain performs a crucial role in the import
      process by enhancing the import motor function of Ssc1 during polypeptide
      translocation.

PMID- 14643669
TI  - Computational design and characterization of a monomeric helical dinuclear
      metalloprotein.
AB  - The de novo design of di-iron proteins is an important step towards understanding
      the diversity of function among this complex family of metalloenzymes. Previous
      designs of due ferro (DF) proteins have resulted in tetrameric and dimeric four
      helix bundles having crystallographically well-defined structures and active-site
      geometries. Here, the design and characterization of DFsc, a 114 residue
      monomeric four-helix bundle, is presented. The backbone was modeled using
      previous oligomeric structures and appropriate inter-helical turns. The
      identities of 26 residues were predetermined, including the primary and secondary
      ligands in the active site, residues involved in active site accessibility, and
      the gamma beta gamma beta turn between helices 2 and 3. The remaining 88 amino
      acid residues were determined using statistical computer aided design, which is
      based upon a recent statistical theory of protein sequences. Rather than sampling
      sequences, the theory directly provides the site-specific amino acid
      probabilities, which are then used to guide sequence design. The resulting
      sequence (DFsc) expresses well in Escherichia coli and is highly soluble.
      Sedimentation studies confirm that the protein is monomeric in solution. Circular
      dichroism spectra are consistent with the helical content of the target
      structure. The protein is structured in both the apo and the holo forms, with the
      metal-bound form exhibiting increased stability. DFsc stoichiometrically binds a
      variety of divalent metal ions, including Zn(II), Co(II), Fe(II), and Mn(II),
      with micromolar affinities. 15N HSQC NMR spectra of both the apo and Zn(II)
      proteins reveal excellent dispersion with evidence of a significant structural
      change upon metal binding. DFsc is then a realization of complete de novo design,
      where backbone structure, activity, and sequence are specified in the design
      process.

PMID- 14643670
TI  - Sub-families of alpha/beta barrel enzymes: a new adenine deaminase family.
AB  - No gene coding for an adenine deaminase has been described in eukaryotes.
      However, physiological and genetical evidence indicates that adenine deaminases
      are present in the ascomycetes. We have cloned and characterised the genes coding
      for the adenine deaminases of Aspergillus nidulans, Saccharomyces cerevisiae and
      Schizosaccharomyces pombe. The A.nidulans gene was expressed in Escherichia coli
      and the purified enzyme shows adenine but not adenosine deaminase activity. The
      open reading frames coded by the three genes are very similar and obviously
      related to the bacterial and eukaryotic adenosine deaminases rather than to the
      bacterial adenine deaminases. The latter are related to allantoinases, ureases
      and dihydroorotases. The fungal adenine deaminases and the homologous adenosine
      deaminases differ in a number of residues, some of these being clearly involved
      in substrate specificity. Other prokaryotic enzymes in the database, while
      clearly related to the above, do not fit into either sub-class, and may even have
      a different specificity. These results imply that adenine deaminases have
      appeared twice in the course of evolution, from different ancestral enzymes
      constructed both around the alpha/beta barrel scaffold.

PMID- 14643672
TI  - Dispersal and colonisation, long and short chronologies: how continuous is the
      Early Pleistocene record for hominids outside East Africa?
AB  - This paper examines the evidence for hominids outside East Africa during the
      Early Pleistocene. Most attention has focused recently on the evidence for or
      against a late Pliocene dispersal, ca. 1.8 Ma., of hominids out of Africa into
      Asia and possibly southern Europe. Here, the focus is widened to include North
      Africa as well as southern Asia and Europe, as well as the evidence in these
      regions for hominids after their first putative appearance ca. 1.8 Ma. It
      suggests that overall there is very little evidence for hominids in most of these
      regions before the Middle Pleistocene. Consequently, it concludes that the
      colonising capabilities of Homo erectus may have been seriously over-rated, and
      that even if hominids did occupy parts of North Africa, southern Europe and
      southern Asia shortly after 2 Ma, there is little evidence of colonisation.
      Whilst further fieldwork will doubtless slowly fill many gaps in a poorly
      documented Lower Pleistocene hominid record, it appears premature to conclude
      that the appearance of hominids in North Africa, Europe and Asia was
      automatically followed by permanent settlement. Rather, current data are more
      consistent with the view that Lower Pleistocene hominid populations outside East
      Africa were often spatially and temporally discontinuous, that hominid expansion
      was strongly constrained by latitude, and that occupation of temperate latitudes
      north of latitude 40 degrees was largely confined to interglacial periods.

PMID- 14643673
TI  - A reassessment of living hominoid postcranial variability: implications for ape
      evolution.
AB  - In an analysis of hominoid postcranial variation, 'Evol. Anthrop. 6 (1998) 87'
      argued that many purportedly unique features of the hominoid postcranium are
      actually much more variable than previously reported and in many instances
      overlap with both suspensory (Ateles) and non-suspensory primates. Based on these
      results, it was concluded that parallelism in the living ape postcranium was a
      plausible and even likely possibility given the Miocene hominoid postcranial
      record. However, this analysis did not distinguish whether within-hominoid
      variability or overlap with non-hominoids involved one or all ape taxa, a
      distinction which has potentially important effects on the interpretation of
      results. To address this issue, primate postcranial morphometric data from the
      trunk and forelimb were reanalyzed using three techniques: cladistic analysis,
      principle components analysis, and cluster analysis. Results reveal that these
      postcranial characters distinguish not only suspensory and quadrupedal primates
      but also discriminate hominoids and Ateles from all other taxa, great apes from
      lesser apes and Ateles, cercopithecines from colobines, and cercopithecoids from
      platyrrhines. The majority of hominoid variability and overlap with Ateles occurs
      with Hylobates humeral head and shoulder joint characters related to brachiation.
      This suggests that Hylobates' specializations may skew analyses of hominoid
      postcranial uniqueness and variability, and that great apes are relatively
      similar in their postcranium.

PMID- 14643674
TI  - First Neanderthal remains from Greece: the evidence from Lakonis.

PMID- 14643676
TI  - Expression and localization of components of the histone deacetylases
      multiprotein repressory complexes in the mouse preimplantation embryo.
AB  - DNA methylation had been implicated in the assembly of multiprotein repressory
      complexes that affect chromatin architecture thereby rendering genes inactive.
      Proteins containing methyl binding domains (MBDs) are major components of these
      complexes. MBD3 is a component of the HDAC associated chromatin remodeling
      complex Mi2/NuRD. The addition of MBD2 to the Mi2/NuRD complex creates MeCP1, a
      complex that is known to inactivate methylated promoters. The undermethylated
      state of the mouse preimplantation embryo prompted us to investigate the known
      repressory complexes at this developmental stage. We found individual components
      of Mi2/NuRD: MBD3, Mi2, HDAC1 and HDAC2 to be expressed from a very early stage
      of embryo development and to localize in close proximity with each other and with
      constitutive heterochromatin by the blastula stage. Expression of MBD2, a
      component of MeCP1, starts in the blastula stage. Then it is also found to be in
      proximity with heterochromatin (based on DAPI staining) and with MBD3, Mi2 and
      HDAC1. In contrast, expression of MeCP2, an MBD containing component of a third
      repressory complex (MeCP2/Sin3A), is not seen in the preimplantation embryo. Our
      results suggest that both Mi2/NuRD and MeCP1 complexes are already present at the
      very early stages of embryo development, while a MeCP2 complex is added to the
      arsenal of repressory complexes post-implantation at a stage when DNA methylation
      takes place.

PMID- 14643677
TI  - Pmel17 expression is Mitf-dependent and reveals cranial melanoblast migration
      during murine development.
AB  - In situ hybridization (ISH) analysis of the murine melanosomal gene, Pmel17,
      demonstrated robust expression in the presumptive retinal pigmented epithelium
      (RPE) starting at E9.5, and in neural crest-derived melanoblasts starting at
      E10.5. Pmel17 expression is not detectable in embryos mutated for Microphthalmia
      associated transcription factor (Mitf), demonstrating transcriptional dependence
      of Pmel17 on Mitf in the RPE. Pmel17 expression in dorsal regions precedes
      dopachrome tautomerase (Dct) ISH expression, suggesting Pmel17 identifies
      melanoblasts at an earlier developmental stage. Dorsally localized Pmel17
      positive cells at the forebrain/midbrain and midbrain/hindbrain boundaries at
      E10.5 reveal migratory pathways for cranial melanoblasts that have not been
      previously described in mouse using Dct expression.

PMID- 14643679
TI  - Temporally regulated expression of Lin-28 in diverse tissues of the developing
      mouse.
AB  - The gene lin-28 was originally identified through a mutant of the nematode
      Caenorhabditis elegans displaying defects in developmental timing. It is
      expressed stage-specifically in tissues throughout the animal and is required for
      cell fates to be expressed at the appropriate stage of larval development. lin-28
      encodes a cytoplasmic protein with a unique pairing of RNA-binding motifs.
      Diverse animals possess Lin-28 homologues and mouse Lin-28 is expressed in
      embryos, embryonic stem cells and embryonal carcinoma cells, but not in some
      differentiated cell types. To assess whether mammalian Lin-28 may function as a
      developmental timing regulator, we examined adult and embryonic tissues of the
      mouse for its expression. We observed Lin-28 protein in many diverse tissues of
      the embryo through the period of organogenesis and that it persists in some
      tissues in the adult. In addition to an overall down-regulation during
      embryogenesis, in at least two tissues Lin-28 expression shows temporal
      regulation, as opposed to cell type or tissue-specific regulation: in the
      developing bronchial epithelium, where it is present in the developing lung and
      absent in the adult, and in a subset of cells developing along the crypt-villus
      axis of the intestine. Interestingly, unlike epithelia, cardiac and skeletal
      muscle continuously express Lin-28, suggesting an ongoing need for its activity
      there. We also observed that Lin-28 expression is repressed during the retinoic
      acid-induced differentiation of mouse P19 cells into neuronal cells, suggesting
      that down-regulation of Lin-28 in some tissues may occur in response to hormonal
      signals that govern development.

PMID- 14643678
TI  - Expression of Zfhep/deltaEF1 protein in palate, neural progenitors, and
      differentiated neurons.
AB  - Zfhep/deltaEF1 is essential for embryonic development. We have investigated the
      expression pattern of Zfhep protein during mouse embryogenesis. We show
      expression of Zfhep in the mesenchyme of the palatal shelves, establishing
      concordance of expression with the reported cleft palate of the deltaEF1-null
      mice. Zfhep protein is strongly expressed in proliferating progenitors of the
      nervous system. In most regions of the brain, post-mitotic cells stop expressing
      Zfhep when they migrate out of the ventricular zone (VZ) and differentiate.
      However, in the hindbrain, Zfhep protein is also highly expressed in post-mitotic
      migratory neuronal cells of the precerebellar extramural stream that arise from
      the neuroepithelium adjacent to the lower rhombic lip. Also, Zfhep is expressed
      as cells migrate from a narrow region of the pons VZ towards the trigeminal
      nucleus. Co-expression with Islet1 shows that Zfhep is expressed in motor neurons
      of the trigeminal nucleus of the pons, but not in the inferior olive motor
      neurons at E12.5. Therefore, Zfhep is strongly expressed in a tightly regulated
      pattern in proliferating neural stem cells and a subset of neurons. Zfhep protein
      is also strongly expressed in trigeminal ganglia, and is moderately expressed in
      other cranial ganglia. In vitro studies have implicated Zfhep as a repressor of
      myogenesis, however, we find that Zfhep protein expression increases during
      muscle differentiation.

PMID- 14643680
TI  - Slitrk6 expression profile in the mouse embryo and its relationship to that of
      Nlrr3.
AB  - Slitrk6 is a member of the Slitrk family of proteins, which are integral membrane
      proteins possessing two leucine-rich repeat (LRR) domains and a carboxy-terminal
      domain partially similar to that in the trk neurotrophin receptor proteins. Here,
      I show that Slitrk6 is uniquely expressed in various organs, different from other
      Slitrk genes which are predominantly expressed in neural tissues. In the
      developing mouse embryo, Slitrk6 expression was detected in the otic cyst,
      lateral trunk epidermis and its underlying mesenchymal tissue, limb bud,
      maxillary process, pharyngeal arches, cochlea, retina, tongue, tooth primordium,
      central nervous system (CNS), and the visceral organ primordia including of the
      lung, gastrointestinal tract (particularly in the enteric neurons) and pancreas.
      The expression in these organs occurred in a spatially restricted manner. In the
      CNS, the expression was highly compartmentalized in the dorsal thalamus,
      cerebellum and medulla. The expression compartment in the thalamus in which
      Slitrk6 was expressed was closely related to the Gbx2-expressing prosomere 2.
      Interestingly, the Slitrk6 expression in the CNS, cochlea, tongue, tooth
      primordial, and other organs was partially complementary to the expression of
      Nlrr3, which belongs to another family of neuronal LRR-containing transmembrane
      proteins. The complementary expression of the two proteins in the dorsal thalamus
      persisted from E13.5 to the adult stage.

PMID- 14643682
TI  - Pax gene expression in the developing central nervous system of Ciona
      intestinalis.
AB  - We compare the expression patterns in Ciona intestinalis of three members of the
      Pax gene family, CiPax3/7, CiPax6 and Cipax2/5/8. All three genes are expressed
      in restricted patterns in the developing central nervous system. At the tailbud
      stage, CiPax3/7 is present in three patches in the brain and along the posterior
      neural tube, CiPax6 throughout the anterior brain and along the posterior neural
      tube and CiPax2/5/8 in a restricted region of the posterior brain. Double in situ
      hybridisations were used to identify areas of overlap between the expression of
      different genes. This showed that CiPax3/7 overlaps with the boundaries of CiPax6
      expression in the anterior brain, and with CiPax2/5/8 in the posterior brain. The
      overlap between CiPax3/7 and CiPax2/5/8 is unlike that described in the ascidian
      Halocynthia rorezti.

PMID- 14643681
TI  - ALC (adjacent to LMX1 in chick) is a novel dorsal limb mesenchyme marker.
AB  - During dorsal-ventral (DV) patterning of the vertebrate limb, WNT7A is expressed
      in dorsal limb ectoderm and activates the expression of LMX1 (in chick; Lmx1b in
      mouse) in dorsal limb mesenchyme, resulting in the appropriate development of
      dorsal cell fates. These two genes are the only known factors involved in
      directing dorsal patterning and the molecular events that link these two factors
      or that occur downstream of LMX1/1b are unknown. We have isolated a novel chick
      transcript, ALC (adjacent to LMX1 in chick). ALC is located 5.3 kb from the 5'
      end of LMX1 and is transcribed in the opposite direction. It is expressed in a
      sub-set of tissues expressing LMX1, most notably in the dorsal mesenchyme of the
      limb, and thus is the second gene discovered with such a distribution in the
      limb. Misexpression studies with viral constructs show that ALC is downstream of
      WNT7A but not of LMX1. ALC shows no homology to known genes and its function
      remains to be determined. However, similarly placed transcripts occur in the
      human and mouse genomes, and we demonstrate that a mouse transcript is also
      expressed in dorsal limb mesenchyme.

PMID- 14643683
TI  - Cloning and expression of zebrafish neuronal nicotinic acetylcholine receptors.
AB  - We propose to use the zebrafish (Danio rerio) as a vertebrate model to study the
      role of neuronal nicotinic acetylcholine receptors (nAChR) in development. As a
      first step toward using zebrafish as a model, we cloned three zebrafish cDNAs
      with a high degree of sequence similarity to nAChR beta3, alpha2 and alpha7
      subunits expressed in other species. RT-PCR was used to show that the beta3 and
      alpha2 subunit RNAs were present in zebrafish embryos only 2-5hours post
      fertilization (hpf) while alpha7 subunit RNA was not detected until 8hpf,
      supporting the differential regulation of nAChRs during development. In situ
      hybridization was used to localize zebrafish beta3, alpha2, and alpha7 RNA
      expression. nAChR binding techniques were used to detect the early expression of
      two high-affinity [3H]-epibatidine binding sites in 2 days post-fertilization
      (dpf) zebrafish embryos with IC(50) values of 28.6pM and 29.7nM and in 5dpf
      embryos with IC(50) values of 28.4pM and 8.9nM. These studies are consistent with
      the involvement of neuronal nAChRs in early zebrafish development.

PMID- 14643684
TI  - Bhlhb5 is expressed in the CNS and sensory organs during mouse embryonic
      development.
AB  - Basic loop helix transcription factors have been shown to be implicated in the
      specification of various cell types, and many are involved in different aspects
      of neural development. Here we describe the expression of Bhlhb5, belonging to
      the beta3 subfamily, in mouse embryos ranging from 9 to 16.5dpc. Bhlhb5 is
      initially detected at 9.5dpc in the neural tube, restricted to longitudinal
      ventral columns of neurons, extending from the hindbrain to the caudal spinal
      cord. At later stages the expression is maintained in the central nervous system,
      in particular in the brain, where it is detected in the outer and more mature
      layer of the forming cerebral cortex and in the spinal cord. In addition Bhlhb5
      is expressed in the developing eye and hair follicles, in the epithelial layer of
      the cochlea in the developing inner, and in the nasal epithelium.

PMID- 14643685
TI  - Expression of the Prader-Willi gene Necdin during mouse nervous system
      development correlates with neuronal differentiation and p75NTR expression.
AB  - The expression pattern of Necdin, a gene involved in the etiology of Prader-Willi
      syndrome and a member of the MAGE family of genes, is described during mouse
      nervous system development. Using RNA in situ hybridization, immunohistochemical
      staining, and colocalization with neuronal differentiation markers, we found that
      Necdin RNA and protein are expressed within post-mitotic neurons at all stages
      studied. From E10 to E12, Necdin is detected in all developing neurons, in both
      central and peripheral nervous system, with the highest expression levels in the
      diencephalon and the hindbrain. After E13, Necdin is expressed in specific
      structures of the nervous system, in particular the hypothalamus, the thalamus,
      and the pons, suggesting a specific developmental role therein. In addition,
      Necdin expression is also detected in non-neural tissues, such as the somites,
      the developing limb buds, the first branchial arches, the tong, and the axial
      muscles. Recently, Necdin and other MAGE proteins were found to interact in vitro
      with the intracellular domain of the p75NTR neurotrophin receptor, but this
      interaction has not been validated in vivo. We report here that the spatial and
      temporal expression of p75NTR is included in Necdin expression domain. These
      results are in agreement with Necdin proposed role on cell cycle arrest,
      inhibition of apoptosis and facilitation of neuronal differentiation in vitro,
      and with hypothalamic cellular deficiencies reported in mice with abrogation of
      the Necdin gene. Furthermore, they are also consistent with the putative role of
      Necdin in signaling events promoted by p75NTR during mouse nervous system
      development.

PMID- 14643686
TI  - Developmentally regulated expression of the mouse homologues of the potassium
      channel encoding genes m-erg1, m-erg2 and m-erg3.
AB  - Deciphering the expression pattern of K+ channel encoding genes during
      development can help in the understanding of the establishment of cellular
      excitability and unravel the molecular mechanisms of neuromuscular diseases. We
      focused our attention on genes belonging to the erg family, which is deeply
      involved in the control of neuromuscular excitability in Drosophila flies and
      possibly other organisms. Both in situ hybridisation and RNase Protection Assay
      experiments were used to study the expression pattern of mouse (m)erg1, m-erg2
      and m-erg3 genes during mouse embryo development, to allow the pattern to be
      compared with their expression in the adult. M-erg1 is first expressed in the
      heart and in the central nervous system (CNS) of embryonic day 9.5 (E9.5)
      embryos; the gene appears in ganglia of the peripheral nervous system (PNS)
      (dorsal root (DRG) and sympathetic (SCG) ganglia, mioenteric plexus), in the
      neural layer of retina, skeletal muscles, gonads and gut at E13.5. In the adult m
      erg1 is expressed in the heart, various structures of the CNS, DRG and retina. M
      erg2 is first expressed at E9.5 in the CNS, thereafter (E13.5) in the neural
      layer of retina, DRG, SCG, and in the atrium. In the adult the gene is present in
      some restricted areas of the CNS, retina and DRG. M-erg3 displayed an expression
      pattern partially overlapping that of m-erg1, with a transitory expression in the
      developing heart as well. A detailed study of the mouse adult brain showed a
      peculiar expression pattern of the three genes, sometimes overlapping in
      different encephalic areas.

PMID- 14643687
TI  - Expression of the hyperpolarization-activated cyclic nucleotide-gated cation
      channel HCN4 during mouse heart development.
AB  - HCN4 is a hyperpolarization-activated nucleotide-gated cation channel involved in
      the generation of the I(f) current that drives cardiac pacemaker activity.
      Previous studies have demonstrated that HCN4 is highly expressed in a restricted
      manner in adult sinoatrial (SA) node [Eur. J. Biochem. 268 (2001) 1646]. However,
      its developmental expression pattern is unknown. We have examined expression of
      HCN4 mRNA during mouse heart development. HCN4 mRNA was first detected in the
      cardiac crescent at embryonic day (ED) 7.5. At ED 8 it was symmetrically located
      in the most caudal portion of the heart tube, the sinus venosus where pacemaker
      activity has previously been reported [Am. J. Physiol. 212 (1967) 407]. With
      further development, HCN4 expression became asymmetrically distributed, occupying
      the dorsal wall of the right atria, and was progressively restricted to the
      junction of the right atrial appendage and the superior vena cava. The site of
      HCN4 expression in late embryonic heart coincided with the location of the SA
      node in postnatal and adult heart [Cardiovasc. Res. 52 (2001) 51]. Our results
      suggest that HCN4 may be a unique marker of the developing SA node.

PMID- 14643689
TI  - The cyclooxygenase-2 product prostaglandin E2 modulates cardiac contractile
      function in adult rat ventricular cardiomyocytes.
AB  - Prostaglandin E(2) (PGE(2)), a product of the cyclooxygenase-2 pathway, has been
      shown to increase cardiac output and modulate cardiac contractile function.
      However, whether the cardiac contractile response of PGE(2) is due to its action
      on single ventricular myocytes has not been elucidated. To assess the mechanical
      effect of PGE(2) at the cellular level, adult rat ventricular myocytes were
      isolated and stimulated to contract at 0.5Hz. Mechanical and intracellular Ca(2+)
      properties were evaluated using an IonOptix Myocam analog-to-digital optical
      detection system. Contractile and intracellular Ca(2+) properties were evaluated
      as peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)),
      maximal velocity of shortening or relengthening (+/-dL/dt) and Ca(2+)-induced
      intracellular Ca(2+) fluorescence release (CICR), baseline intracellular Ca(2+)
      levels and intracellular Ca(2+) decay rate (tau). PGE(2) (10(-8) to 10(-3)M)
      elicited an augmentation in PS but had no effect on TPS, TR(90), +/-dL/dt, CICR
      and tau. High concentration of PGE(2) (10(-5)M or higher) reduced the baseline
      intracellular Ca(2+) levels. These data indicate that the myocardial contractile
      response of PGE(2) may be due to its direct cardiac contractile action at the
      single ventricular myocyte level, probably through a mechanism independent of
      intracellular Ca(2+) release.

PMID- 14643690
TI  - Gastroprotective and anti-inflammatory effects of resin from Protium heptaphyllum
      in mice and rats.
AB  - The natural resin collected from the trunk wood of Protium heptaphyllum is used
      in folk medicine to treat inflammatory conditions and to hasten wound repair. In
      the search of new potential anti-inflammatory agents with gastroprotective
      property, the present study evaluated its effects in experimental models of
      gastric ulcer and inflammation. In mice, the resin (200 and 400 mg/kg)
      significantly attenuated the gastric damage induced by ethanol or acidified
      ethanol (HCl/ethanol), in a manner similar to N-acetyl-L-cysteine (NAC), a
      replenisher of sulfhydryls. Unlike NAC the resin failed to restore the ethanol
      induced depletion of non-protein sulfhydryl content, indicating a different
      mechanism of gastroprotection. However, in 4-h pylorus-ligated rats, the resin
      significantly reduced the total acidity without much change in gastric secretory
      volume. In rats, at similar doses the resin did not modify the hind-paw edema
      induced by carrageenan, but effectively reduced the formation of cotton pellet
      induced granuloma, suggesting its inhibitory effect on collagen formation but not
      on acute edema. Furthermore, the vascular permeability increase induced by acetic
      acid was significantly reduced in mice that received 400 mg/kg resin. The resin
      demonstrated no overt toxicity in mice up to an oral dose of 5 g/kg.
      Phytochemical analysis revealed the presence of alpha- and beta-amyrins as
      principal triterpenoid constituents of resin, which were previously described to
      have anti-ulcer property. These findings indicate the potential gastroprotective
      and anti-inflammatory property of P. heptaphyllum resin and further support its
      popular use in gastrointestinal disorders.

PMID- 14643691
TI  - American ginseng leaf: ginsenoside analysis and hypoglycemic activity.
AB  - Previous studies showed that both American ginseng root and American ginseng
      berry extracts possess hypoglycemic properties. In this study, we investigated
      whether American ginseng leaves also have similar capabilities. We first analyzed
      the chemical constituents of American ginseng leaf and determined the content of
      six major ginsenosides, i.e., Rb(1), Rb(2), Rc, Rd, Re, and Rg(1), by high
      performance liquid chromatography (HPLC). Subsequently, we evaluated the
      hypoglycemic effect of American ginseng leaf extract (AGLE) in diabetic ob/ob
      adult mice. Animals received daily intraperitoneal injections of AGLE 50, 150
      mg/kg or vehicle for 12 consecutive days. Fasting blood glucose levels,
      intraperitoneal glucose tolerance test (IPGTT), body weight and temperature were
      measured. On day 5, the 150 mg/kg AGLE group had significantly lower fasting
      blood glucose levels compared to vehicle-treated mice (223.0+/-13.9 mg/dl versus
      258.0+/-14.0 mg/dl, P<0.05), while the blood glucose levels in 50 mg/kg group did
      not decrease significantly. On day 12, the glucose levels in both AGLE-treated
      groups were reduced significantly compared to vehicle group (180.0+/-10.0 mg/dl
      and 220.2+/-19.3 versus 268.0+/-10.0 mg/dl, P<0.01 and <0.05, respectively).
      IPGTT data showed that both AGLE 150 and 50 mg/kg groups significantly increased
      the glucose disposal on day 12 compared to the vehicle group. In addition, body
      weight decreased in ob/ob mice after AGLE treatment, and these body weight
      changes were accompanied by significant increases in body temperature (P<0.05).
      Our results suggest that AGLE possesses a significant anti-hyperglycemic and
      thermogenic activity and may prove to be beneficial in improving the management
      of type 2 diabetes.

PMID- 14643692
TI  - Studies on the anti-inflammatory effect of fluoxetine in the rat.
AB  - The anti-inflammatory activity of fluoxetine, a selective serotonin reuptake
      inhibitor (SSRI), was studied on the carrageenan-induced paw inflammation in the
      rat. Fluoxetine (10-60 mg kg(-1)) given intraperitoneally (i.p.) 30 min before
      carrageenan, displayed marked anti-inflammatory activity, inhibiting paw oedema
      by 38.6-77.7% at 2 h post-carrageenan. Fluoxetine administered at time of
      carrageenan injection or 30 min after carrageenan challenge, markedly inhibited
      the paw oedema response. Rats administered daily fluoxetine (20 mg kg(-1), i.p.)
      showed significantly decreased inflammatory response to subplantar carrageenan
      when examined on the 5th and 14th day of fluoxetine injection. Fluoxetine (10 or
      20 mg kg(-1), i.p.) co-administered with indomethacin (IND) (20 mg kg(-1), i.p.),
      celecoxib (10 mg kg(-1), i.p.) or rofecoxib (4.5 mg kg(-1), i.p.) before
      carrageenan reduced the anti-oedema effect of indomethacin or celecoxib, but had
      additive effect to that of rofecoxib. The anti-oedema effects of fluoxetine and
      melatonin or the tricyclic antidepressant imipramine were additive. In contrast,
      administration of both fluoxetine and the heterocyclic antidepressant trazodone
      had no greater anti-inflammatory effect than fluoxetine alone. The anti-oedema
      effect of fluoxetine was partially suppressed by the opioid antagonist naloxone
      (4 mg kg(-1), i.p.). Fluoxetine (360 or 720 microg per paw) given into the rat
      paw with carrageenan reduced the oedema response by 25.4 and 35.3% 4 h post
      carrageenan, respectively. It is suggested that fluoxetine alone or co
      administered with either imipramine or melatonin would be of benefit in the
      sitting of neuropathic or inflammatory pain conditions. Both the serotonergic and
      the opioid systems are likely to be involved in the modulating action of
      fluoxetine on peripheral inflammation.

PMID- 14643693
TI  - Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of
      Ginkgo biloba in the rat.
AB  - Ginkgo biloba extract (GbE) was assessed in models of acute inflammation induced
      by carrageenan, formalin or capsaicin in the rat, in models of nociceptive pain,
      such as hot-plate (55 degrees C) latency, tail-electric stimulation assay and
      capsaicin-induced paw licking and in the model of acute gastric damage induced by
      indomethacin. The agent showed marked anti-inflammatory activity in the
      carrageenan model of paw oedema. When given subcutaneously (s.c.) (25 and 50 mg
      kg(-1)) 30 min before challenge, GbE inhibited paw oedema with a maximal effect
      of 43.7 and 56.9%, respectively, at 2h post-carrageenan. Significant inhibition
      of oedema was also observed when GbE (50 mg kg(-1), s.c.) was given 30 min after
      carrageenan challenge. The agent was also active p.o. in acute inflammation
      caused by carrageenan. The administration of GbE with indomethacin, rofecoxib,
      celecoxib, dexamethasone or melatonin resulted in an additive effect. GbE (50 mg
      kg(-1), s.c.) caused significant inhibition of formalin-induced paw oedema, but
      did not reduce the capsaicin-induced paw oedema. In tests of nociception, GbE
      (25, 50 or 100 mg kg(-1)) decreased in dose-dependent manner the capsaicin
      induced hind paw licking time and was similarly effective in the hot-plate assay
      of nociception. In contrast, when assessed in the tail-electric stimulation test,
      GbE was only effective in the highest dose (100 mg kg(-1)). In pylorus-ligated
      rats, GbE (25 or 50 mg kg(-1)) increased gastric acid secretion, but reduced
      gastric mucosal damage caused by IND. Results suggest that GbE may be of clinical
      value as an anti-inflammatory and analgesic drug alone or in conjunction with
      NSAIDs.

PMID- 14643694
TI  - Nimodipine attenuates biochemical, behavioral and histopathological alterations
      induced by acute transient and long-term bilateral common carotid occlusion in
      rats.
AB  - Restoration of blood flow to an ischemic brain region is associated with
      generation of reactive oxygen species with consequent reperfusion injury. Chronic
      cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid
      arteries in rats is associated with behavioral and histopathological alterations.
      Nimodipine, a dihydropyridine calcium channel antagonist, has potent vasodilatory
      effect on cerebral vessels and increases cerebral blood flow. We analyzed whether
      nimodipine reduces injury caused by transient forebrain ischemia and long-term
      cerebral hypoperfusion. Bilateral common carotid occlusion for 30 min followed by
      45 min reperfusion resulted in a two-fold increase in lipid peroxidation and
      superoxide dismutase activity. Nimodipine pretreatment (4 mg/kg, i.p.) brought
      down these levels by 30 and 23%, respectively. Long-term cerebral hypoperfusion
      in rats caused a propensity towards anxiety and listlessness (open field
      paradigm) accompanied by deficits of learning and memory (Morris' water maze
      testing). Additionally, histopathological observation in hypoperfused brains
      revealed reactive changes in the form of perivascular inflammation, gliosis and
      astrocytosis. Nimodipine treatment significantly alleviated these changes in
      behavioral and histopathological parameters. Our data confirm the protective role
      of nimodipine in ischemia reperfusion injury. Moreover, it suggests the
      beneficial role of nimodipine in cerebrovascular insufficiency states and
      dementia.

PMID- 14643695
TI  - Effects of steroid hormones on (Na+, K+)-ATPase activity inhibition-induced
      amnesia on the step-through passive avoidance task in gonadectomized mice.
AB  - Inhibition of sodium-potassium adenosine 5'-triphosphatase ((Na(+), K(+))-ATPase)
      activity causes edema and cell death in the central nervous system, and
      impairment of learning and memory. Several sex steroid hormones have a protective
      effect against neuronal cell damage and the hypofunction of learning and memory.
      To examine the possible roles and mechanism of action of steroid hormones against
      amnesia induced by ouabain, an inhibitor of (Na(+), K(+))-ATPase, gonadectomized
      male mice were administrated ouabain (0.1 microg per mouse) intracisternally
      (i.cist.), and the learning and memory abilities of the mice were assessed by a
      step-through passive avoidance task. Subcutaneous (s.c.) administration of 17beta
      estradiol (betaE2; 10 microg kg(-1)) or testosterone (TES; 1 mg kg(-1)) improved
      the memory impairment induced by ouabain, while administration of
      dihydrotestosterone (1 mg kg(-1)) or corticosterone (COR) (1 mg kg(-1)) did not.
      Treatment with the estradiol receptor antagonists, tamoxifen (TAM) (10 mg kg(-1);
      s.c. or 0.1 microg; i.cist.) and 4-hydroxytamoxifen (10 mg kg(-1); s.c.), or the
      androgen receptor antagonist, cyproterone (10 mg kg(-1); s.c. or 1 microg;
      i.cist.), did not influence the protective effect of betaE2 or TES on ouabain
      induced amnesia. Moreover, we studied the effects of several free radical
      scavengers-17alpha-estradiol (10 microg kg(-1); s.c.), alpha-tocopherol (VE: 200
      mg kg(-1); per os (p.o.), ascorbic acid (VC: 200 mg kg(-1); p.o.), or VE+VC (200
      mg kg(-1) each; p.o.)-on ouabain-induced amnesia, and compared those effects with
      that of betaE2. The administration of free radical scavengers had no significant
      effect on memory impairment. These results indicate that betaE2 and TES
      ameliorate the amnesia induced by inhibition of (Na(+), K(+))-ATPase activity,
      and that the protective effect of betaE2 is caused by a non-genomic, rather than
      a genomic effect or a radical scavenging action. Additionally, the ameliorative
      effect of TES does not appear to involve free radical scavenging, but its
      aromatization to estrogen could contribute to the non-genomic action of betaE2.

PMID- 14643696
TI  - Cancer chemopreventive effect of phenothiazines and related tri-heterocyclic
      analogues in the 12-O-tetradecanoylphorbol-13-acetate promoted Epstein-Barr virus
      early antigen activation and the mouse skin two-stage carcinogenesis models.
AB  - In continuation of our search for novel agents, we have investigated 29
      phenothiazines and related tri-heterocyclic compounds as potential cancer
      chemopreventive agents in a short-term in vitro assay of Epstein-Barr virus early
      antigen (EBV-EA) activation induced by the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA). Among the evaluated compounds,
      chlorpromazine, phenoxazine, ethylpropazine, 9-oxo-9H-thioxanthene-3-carbonitrile
      10,10-dioxide, thiothixene and phenothiazine showed profound inhibition of EBV-EA
      in the in vitro assay. This activity was influenced by a modification of the
      phenothiazine ring. Replacement of nitrogen in the phenothiazine ring with sulfur
      atoms decreased the anti-tumor activity. Overall analysis showed that the simple
      tri-cyclic compound phenoxazine was the most active anti-tumor promoting compound
      in the test system. Therefore, we assessed the anti-tumor promoting effect of
      phenoxazine in vivo in two different chemical carcinogen-induced-promotion
      experimental models in mice namely the 7,12-dimethylbenz(a)anthracene (DMBA)
      initiated and TPA-promoted ICR mouse skin two-stage carcinogenesis protocol and
      the peroxynitrite (PN)-induced and TPA-promoted skin carcinogenesis in HOS:HR-1
      mouse. Following tumor initiation with DMBA, topical application of 0.0025%
      phenoxazine to the dorsal initiated mouse skin resulted in a highly significant
      inhibition of TPA tumor promotion. The compound exhibited remarkable inhibitory
      effects on the mouse skin tumor promotion in terms of a reduction in tumor
      multiplicity (>50%) and incidence, accompanied by an extension of the tumor
      latency. In the PN-induced and TPA-promoted two-stage mouse skin carcinogenesis,
      oral administration of phenoxazine (0.0025%) for 2 weeks showed profound decrease
      in both the tumor incidence and burden by more than 20 and 80%, respectively, at
      10 weeks of treatment. This was also accompanied by a 20% delay in the tumor
      latency period. In all the treatment groups, there was no toxicity due to
      phenoxazine in the treatment groups as compared to the control animals. These
      significant anti-tumor potentials of phenoxazine either via topical or oral
      administration might be due to the inherent cytotoxicity of these classes of
      compounds, which can be utilized in the prevention of development of overt
      tumors, immunopotentiation, induction of differentiation and apoptosis. In
      addition, since phenoxazine derivatives and other related phenothiazine compounds
      in use, as anti-psychotic agents without any reported adverse effect are known to
      pass the blood-brain barrier, they represent a new class of cancer
      chemopreventive agents with greater implication in the prevention of brain
      cancers.

PMID- 14643697
TI  - Safety of azamethiphos in eel, seabass and trout.
AB  - The safety of azamethiphos (AZA), an organophosphorous insecticide and the active
      ingredient of Salmosan, was evaluated in the European eel, seabass and rainbow
      trout. Fish were bathed in 0.1 ppm AZA for a period of 60, 120 or 240 min. After
      termination of each treatment fish were transferred to clean aquaria and randomly
      sampled over 21 days. Compared to controls, brain acetylcholinesterase (AChE) was
      inhibited up to 44, 56 and 62% in eels, seabass and trout, respectively, with the
      inhibition being significant for up to 4 days in eels and seabass and 7 days in
      trout. As result of the AChE depression, fish displayed motor hyperactivity and
      erratic jumping at the onset of treatment. Mortality was observed only in trout
      following exposure for 240 min. A variable correlation observed among species
      between the level of exposure, the reduced activity of brain AChE and the signs
      of toxicity suggest that brain AChE should be considered as an indicator of
      exposure rather than as an index of toxicity of AZA. The present data indicate
      that at the therapeutic dosage of 0.1 ppm AZA for 1h can be safely used in eels,
      seabass and trout. The extended treatment times up to 240 min were equally safe
      for eels and seabass but not for trout.

PMID- 14643698
TI  - Pharmacokinetic studies of a novel anticonvulsant, 2-(4-chlorophenyl)amino-2-(4
      pyridyl)ethane, in rats.
AB  - The pharmacokinetic properties of 2-(4-chlorophenyl)amino-2-(4-pyridyl)ethane
      (AAP-Cl) were studied in rats after intravenous and oral administration. The
      blood concentrations of AAP-Cl in rats showed a biexponential decline following
      intravenous administration of pharmacologic doses ranging from 10 to 100 mg/kg in
      rats. The terminal elimination half-lives (t((1/2)beta)) of AAP-Cl at the 10, 50
      and 100 mg/kg dose levels were 5.80+/-0.30, 6.02+/-0.16 and 6.05+/-0.08 h,
      respectively. The total clearances (CL) of AAP-Cl at the 10, 50 and 100 mg/kg
      dose levels were 1.29+/-1.10, 1.38+/-0.07 and 1.33+/-0.13l/(h kg), respectively.
      The apparent volumes of distribution at steady state (V(ss)) of AAP-Cl at the 10,
      50 and 100 mg/kg dose levels were 7.96+/-0.51, 8.24+/-0.31 and 8.17+/-0.43l/kg,
      respectively. The AUC(0-infinity) increased proportionately to the intravenous
      bolus dose of AAP-Cl given (10-100 mg/kg). Statistical analysis of the
      t((1/2)beta), V(ss) and CL values for AAP-Cl between doses indicates that AAP-Cl
      exhibits dose-independent kinetics (P>0.05). AAP-Cl was absorbed rapidly after an
      oral dose of 100 mg/kg with peak concentrations (C(max)) in blood (3.5+/-0.33
      microg/ml) reached after 30 min of drug administration. The oral bioavailability
      of AAP-Cl was 19.5+/-3.4% following administration of a single 100 mg/kg dose in
      rats. Urine analysis indicates that 2.5+/-0.45% of the administered dose of AAP
      Cl (100 mg/kg, p.o.) is recovered unchanged in urine within 0-24 h. These
      findings may be useful in designing new aminoalkylpyridine anticonvulsants with
      improved efficacy and disposition profiles in animal models of epilepsy.

PMID- 14643699
TI  - Pharmaco attributes of dioleoylphosphatidylethanolamine/cholesterylhemisuccinate
      liposomes containing different types of cleavable lipopolymers.
AB  - Various amounts of one of three different types of cleavable methoxy polyethylene
      glycol (mPEG)-phospholipids or of a non-cleavable counterpart (mPEG-DSPE) were
      included into pH-sensitive liposome formulations containing
      dioleoylphosphatidylethanolamine (DOPE) and cholesterylhemisuccinate (CHEMS) at a
      6:4 molar ratio, and the effect on plasma clearance and contents release rates
      was determined. The cleavable lipopolymers were all based on a
      distearoylphosphatidyl lipid anchor, which was linked to mPEG via
      dithiodipropionateaminoethanol (mPEG-DTP-DSPE), dithio-3-hexanol (mPEG-DTH-DSPA),
      or Gly-Phe-Leu-Gly-aminoethanol (mPEG-GFLG-DSPE) linkers. In contrast to the
      first-generation thiolytically cleavable lipopolymer, mPEG-DTP-DSPE, the second
      generation conjugates contained a hindered disulfide or enzymatically cleavable
      tetrapeptide, respectively, as the points of scission. In the absence of mPEG
      lipid, DOPE/CHEMS liposomes had rapid clearance half-lives. As the mol% of mPEG
      lipid in the liposomes increased, the rate of clearance of DOPE/CHEMS liposomes
      in mice decreased. Zeta-potential measurements showed that decreased clearance
      was correlated with a decrease in the apparent surface charge of the liposomes,
      which approached neutrality as the content of mPEG-lipids increased to above 15
      mol%. At these levels, liposomes containing mPEG-DTP-DSPE were cleared from blood
      circulation faster than liposomes containing other, less vulnerable lipopolymers.
      Liposomes with the peptide-linked lipopolymer exhibited the slowest clearance.
      The presence of either cleavable or non-cleavable mPEG-lipids at concentrations
      of 5 mol% or higher in the DOPE/CHEMS liposomes inhibited the release of
      doxorubicin from these liposomes in response to acid pH.

PMID- 14643700
TI  - Definition of displacement probability and diffusion time in q-space magnetic
      resonance measurements that use finite-duration diffusion-encoding gradients.
AB  - In q-space diffusion NMR, the probability P(r,td) of a molecule having a
      displacement r in a diffusion time td is obtained under the assumption that the
      diffusion-encoding gradient g has an infinitesimal duration. However, this
      assumption may not always hold, particularly in human MRI where the diffusion
      encoding gradient duration delta is typically of the same order of magnitude as
      the time offset Delta between encoding gradients. In this case, finite-delta
      effects complicate the interpretation of displacement probabilities measured in q
      space MRI, and the form by which the signal intensity relates to them. By
      considering the displacement-specific dephasing, <r/eiphi>, of a set of spins
      accumulating a constant displacement vector r in the total time Delta+delta
      during which diffusion is encoded, the probability recovered by a finite-delta q
      space experiment can be interpreted. It is shown theoretically that a data
      analysis using a modified q-space index q=gammadeltaetag, with gamma the
      gyromagnetic ratio and eta=square root (Delta-delta/3)/(Delta+delta), recovers
      the correct displacement probability distribution if diffusion is multi-Gaussian
      free diffusion. With this analysis, we show that the displacement distribution
      P(r,texp) is measured at the experimental diffusion-encoding time
      texp=Delta+delta, and not at the reduced diffusion time tr=Delta-delta/3 as is
      generally assumed in the NMR and MRI literature. It is also shown that, by
      defining a probability P(y,Delta) that a time t<delta exists such that a
      displacement y occurs from time t to t+Delta, it is possible to describe the
      physical significance of the result obtained when we use the q-space formalism
      valid for infinitesimal delta when delta is not infinitesimal. These deductions
      were confirmed by simulations for homogeneous Gaussian diffusion and for
      heterogeneous diffusion in permeable microscopic Gaussian domains that are
      homogeneous on the microm scale. The results also hold for diffusion inside
      restricted spherical reflecting domains, but only if the radius of the domain is
      larger than a critical size. The simulations of the displacement-specific
      dephasing obtain that if delta>deltac then eta is not equal to square root (Delta
      delta/3)/(Delta+delta) which implies that we can no longer obtain the correct
      displacement probability from the displacement distribution. In the case that
      /g/=18 mT/m and Delta-delta=5 ms, the parameter deltac in ms is given by
      "deltac=0.49a2+0.24" where a is the sphere's radius expressed in microm.
      Simulation of q-space restricted diffusion MRI experiments indicate that if
      eta=square root (Delta-delta/3)/(Delta+delta), the recovered displacement
      probability is always better than the Gaussian approximation, and the measured
      diffusion coefficient matches the diffusion coefficient at time texp=Delta+delta
      better than it matches the diffusion coefficient at time tr=Delta-delta/3. These
      results indicate that q-space MRI measurements of displacement probability
      distributions are theoretically possible in biological tissues using finite
      duration diffusion-encoding gradients provided certain compartment size and
      diffusion encoding gradient duration constraints are met.

PMID- 14643701
TI  - Actively shielded multi-layer gradient coil designs with improved cooling
      properties.
AB  - In standard cylindrical gradient coils consisting of a single layer of wires, a
      limiting factor in achieving very large magnetic field gradients is the rapid
      increase in coil resistance with efficiency. This is a particular problem in
      small-bore scanners, such as those used for MR microscopy. By adopting a multi
      layer design in which the coil wires are allowed to spread out into multiple
      layers wound at increasing radii, a more favourable scaling of resistance with
      efficiency is achieved, thus allowing the design of more powerful gradient coils
      with acceptable resistance values. Previously this approach has been applied to
      the design of unshielded, longitudinal, and transverse gradient coils. Here, the
      multi-layer approach has been extended to allow the design of actively shielded
      multi-layer gradient coils, and also to produce coils exhibiting enhanced cooling
      characteristics. An iterative approach to modelling the steady-state temperature
      distribution within the coil has also been developed. Results indicate that a
      good level of screening can be achieved in multi-layer coils, that small versions
      of such coils can yield higher efficiencies at fixed resistance than conventional
      two-layer (primary and screen) coils, and that performance improves as the number
      of layers of increases. Simulations show that by optimising multi-layer coils for
      cooling it is possible to achieve significantly higher gradient strengths at a
      fixed maximum operating temperature. A four-layer coil of 8 mm inner diameter has
      been constructed and used to test the steady-state temperature model.

PMID- 14643702
TI  - Fast-MAS total through-bond correlation spectroscopy using adiabatic pulses.
AB  - Pulse sequences consisting of adiabatic pulses for total through-bond correlation
      spectroscopy (TOBSY) under magic-angle spinning (MAS) are introduced. Above a
      certain threshold, the polarization transfer achieved with these sequences is
      largely insensitive to the amplitude and homogeneity of the radiofrequency field
      employed. An experimental transfer efficiency of up to 76% was achieved in a two
      spin system using the sequence WiW9(24)(1) at a MAS frequency of 26.67 kHz.
      Applications to resonance assignments in the dipeptide L-Val-L-Phe and in the
      cyclic decapeptide antamanide are demonstrated.

PMID- 14643703
TI  - Centric scan SPRITE magnetic resonance imaging.
AB  - Two rapid, pure phase encode, centric scan, Single Point Ramped Imaging with T1
      Enhancement (SPRITE) MRI methods are described. Each retains the benefits of the
      standard SPRITE method, most notably the ability to image short T2* systems,
      while increasing the sensitivity and generality of the technique. The Spiral
      SPRITE method utilizes a modified Archimedean spiral k-space trajectory. The
      Conical-SPRITE method utilizes a system of spirals mapped to conical surfaces to
      sample the k-space cube. The sampled k-space points are naturally Cartesian grid
      points, eliminating the requirement of a re-gridding procedure prior to image
      reconstruction. The effects of transient state behaviour on image resolution and
      signal/noise are explored.

PMID- 14643704
TI  - Compensating for pulse imperfections in REDOR.
AB  - Rotational-echo double resonance (REDOR) is a magic-angle spinning technique for
      measuring heteronuclear dipolar couplings. Rotor-synchronized pi pulses recouple
      the dipolar interaction. The accuracy of a REDOR determination of distance or
      orientation depends totally on the quality of the dephased (recoupled) and full
      echo spectra. We present a scheme for measuring and compensating for the effects
      of pulse imperfections in REDOR experiments. No assumptions are made about the
      quality of the pi pulses, and no pulses are added or taken away in implementing
      the compensation for incomplete REDOR dephasing by imperfect pi pulses.

PMID- 14643705
TI  - NMR assignment of protein side chains using residue-correlated labeling and NOE
      spectra.
AB  - A new approach for the isotopic labeling of proteins is proposed that aims to
      facilitate side chain resonance assignments. Residue-correlated (RC) labeling is
      achieved by the expression of a protein on a medium containing a mixture of
      labeled, e.g., [U-13C,15N]amino acids, and NMR silent, [U-2H]amino acids. De novo
      synthesis of amino acids was suppressed by feedback inhibition by the amino acids
      in the growth medium and by the addition of beta-chloro-L-alanine, a transaminase
      inhibitor. Incorporation of these amino acids into synthesized proteins results
      in a relative diminution of inter-residue NOE interactions and a relative
      enhancement of intra-residue NOEs. Comparison of the resulting NOE spectra with
      those obtained from a uniformly labeled sample allows identification of intra
      residue NOE peaks. Thus, this approach provides direct information for sidechain
      assignments in the NOE spectra, which are subsequently used for structural
      analysis. We have demonstrated the feasibility of this strategy for the 143 amino
      acid nuclease inhibitor NuiA, both at 35 degrees C, corresponding to a rotational
      correlation time of 9.5 ns, and at 5 degrees C, corresponding to a rotational
      correlation time of 22 ns.

PMID- 14643706
TI  - A high sensitivity 3D experiment for measuring Calpha-Halpha residual dipolar
      coupling constants.
AB  - A new sensitivity improved approach is presented to measure the Calpha-Halpha
      scalar and dipolar coupling constants in 13C/15N-labeled proteins using a
      HA(CA)CONH scheme. The proposed experiment has significantly higher sensitivity
      than the previously published (HA)CA(CO)NH sequence, and provides accurate and
      straightforward measurements of the scalar and residual dipolar coupling
      constants. The sequence is easy to implement, and has been demonstrated on the C
      terminal domain of the human Ku-80 protein (152 amino acid residues). On average,
      sensitivity is improved by 40% for both isotropic and anisotropic samples. The
      sensitivity enhancement is more pronounced for structured regions than
      unstructured regions, with an average of 50-60% enhancement being observed in the
      well-structured regions of the protein.

PMID- 14643707
TI  - Compensation of refocusing inefficiency with synchronized inversion sweep
      (CRISIS) in multiplicity-edited HSQC.
AB  - Use of adiabatic pulses in broadband inversion and decoupling is well known.
      Replacement of the rectangular pi pulses in the INEPT and rev-INEPT parts of the
      HSQC and gHSQC experiments with adiabatic pulses substantially improves the
      sensitivity of these experiments. However, modulation of cross peak intensity in
      multiplicity-edited HSQC or gHSQC experiments can be quite severe. These
      modulations arise during the multiplicity-editing periods due to the inefficient
      refocusing of the spin-echo caused by the mismatch of the echo delay with the one
      bond coupling constant. These modulations (which we call echo modulations) are
      field strength (and hence spectral width) independent. Use of adiabatic pulses
      with the inversion sweep synchronized to the 1H-13C coupling constant range
      typically observed in a 13C spectrum will provide substantial improvement in
      sensitivity. The inversion profile problems associated with rectangular pi pulses
      can be moderately compensated by composite pulse schemes and these schemes could
      prove to be reasonable alternatives to adiabatic pulses. However, the adiabatic
      sweep provides a unique method to compensate the echo modulations for
      multiplicity-edited experiments. The origin and the compensation of refocusing
      inefficiency with synchronized inversion sweep (CRISIS) method to minimize these
      modulations is described.

PMID- 14643708
TI  - Probing magnetic fields on crystals of the nanomagnet Mn12-acetate by electron
      paramagnetic resonance.
AB  - We report on electron paramagnetic resonance (EPR) probing of magnetic fields and
      magnetic field gradients near the surface of a single crystal of the nanomagnet
      [Mn12O12(CH3COO)16(H2O)4].2CH3COOH.4H2O (Mn12-Ac). As the EPR probe, we utilized
      a 0.7 mm x 30 microm x 30 microm fibrous needle of the organic conductor N
      methylphenazinium-tetracyanoquinodimethane (NMP-TCNQ), which yields an
      exceptionally sharp peak, with a 0.2 G (approximately 20 microT) width. In the
      presence of Mn12-Ac, the probe's peak exhibits splitting on temperature lowering,
      which depends on the orientation of the Zeeman field relative to the axis of easy
      magnetization of the employed Mn12-Ac crystal. The shifted peaks yield the
      magnitude of the magnetic field from Mn12-Ac crystal to which the various fibers
      of the probe are subjected. In conjunction with electron microscopy, the shifts
      yield the field gradient at the crystal surface and its change with temperature.
      For Mn12-Ac at 10 K, the surface magnetic field was measured to be in the mT
      range and its gradient on the order of 50 T/m.

PMID- 14643709
TI  - Determination of water self-diffusion coefficient in complex food products by low
      field 1H PFG-NMR: comparison between the standard spin-echo sequence and the T1
      weighted spin-echo sequence.
AB  - In 1990, Van Den Enden et al. proposed a method for the determination of water
      droplet size distributions in emulsions using a pulsed-field-gradient nuclear
      magnetic resonance (PFG-NMR) T1-weighted stimulated-echo technique. This paper
      describes both the T1-weighted spin-echo sequence, an improved method based on
      this earlier work, and, the standard PFG spin-echo sequence. These two methods
      were compared for water self-diffusion coefficient measurement in the fatty
      protein concentrate sample used as a 'cheese model.' The transversal and
      longitudinal relaxation parameters T1 and T2 were determined according to the
      temperature and investigated for each sample; fat-free protein concentrate
      sample, pure anhydrous milk fat, and fatty protein concentrate sample. The water
      self-diffusion in fat-free protein concentrate samples followed a linear
      behavior. Consequently, the water self-diffusion coefficient could be easily
      characterized for fat-free protein concentrate samples. However, it seemed more
      complicated to obtain accurate water self-diffusion in fatty protein concentrate
      samples since the diffusion-attenuation data were fitted by a bi-exponential
      function. This paper demonstrates that the implementation of the T1-weighted spin
      echo sequence, using the different T1 properties of water and fat phases, allows
      the accurate determination of water self-diffusion coefficient in a food product.
      To minimize the contribution of the 1H nuclei in the fat phase on the NMR echo
      signal, the fat protons were selectively eliminated by an additional 180 degrees
      pulse. This new method reduces the standard errors of diffusion data obtained
      with a basic spin-echo technique, by a factor of 10. The effectiveness of the use
      of the T1-weighted spin-echo sequence to perform accurate water self-diffusion
      coefficients measurement in fatty products is thus demonstrated.

PMID- 14643710
TI  - A new method for suppressing the central transition in I=3/2 NMR spectra with a
      demonstration for 23Na in bovine articular cartilage.
AB  - The splitting and the lineshape of the satellite transitions of 23Na are measures
      of the residual quadrupolar interaction and its distribution, which are related
      to the degrees of order and binding of sodium in biological tissues. However,
      these transitions are often masked by the stronger signals of the central
      transition and the isotropic sodium ions. A way to suppress the central signals,
      while preserving the lineshape and the intensity of the satellites, is suggested
      and tested on a liquid crystal and on bovine articular cartilage.

PMID- 14643711
TI  - 2H chemical shift anisotropies from high-field 2H MAS NMR spectroscopy.
AB  - 2H chemical shift anisotropies (CSAs) have been determined for the first time for
      polycrystalline samples employing 2H MAS NMR spectroscopy at high magnetic field
      strength (14.1 T). The 2H CSA is reflected as distinct asymmetries in the
      manifold of spinning sidebands (ssbs) observed for the two overlapping single
      quantum transitions. Least-squares fitting to the manifold of ssbs allows
      determination of the 2H CSA parameters along with the quadrupole coupling
      parameters. This is demonstrated for KD2PO4, ND4D2PO4, KDSO4, KDCO3, alpha
      (COOD)2, alpha-(COOD)2.2D2O, and boehmite (AlOOD) which exhibit 2H shift
      anisotropies in the range 13< or =deltasigma< or =27 ppm. For fixed values of the
      shift anisotropy and the 2H quadrupole coupling it is shown that the precision of
      the CSA parameters depends strongly on the asymmetry parameter (etaQ) for the
      quadrupole coupling tensor, giving the highest precision for etaQ approximately
      0. The 2H CSA parameters (deltasigma and etasigma) are in good agreement with 1H
      CSA data reported in the literature for the corresponding protonated samples from
      1H NMR spectra employing various homonuclear decoupling techniques. The
      determination of 2H quadrupole coupling parameters and 2H (1H) CSAs from the same
      2H MAS NMR experiment may be particularly useful in studies of hydrogen bonding
      since the 2H quadrupole coupling constant and the CSA appear to characterize bond
      lengths in a hydrogen bond in a different manner.

PMID- 14643712
TI  - Triple quantum nutation in the two-level NMR system in the rotating frame.
AB  - The authors present the detailed theory and the new results associated with the
      triple quantum (TQ) nutation and the line narrowing effect of the TQ resonance in
      the two-level NMR system which we reported previously. The TQ resonance is
      induced in the spin-locked system by the oscillating field produced by the
      sinusoidal phase modulation (PM) of the RF field. The theory predicts that the TQ
      nutation is accompanied by several higher frequency oscillations and we detected
      them experimentally by improving the detection system. These higher frequency
      oscillations are due to the fluctuation of the angle between the transverse or
      effective field causing the TQ nutation and the RF field. We obtain the result
      that the modulation index 2phim of the PM is the key parameter that essentially
      controls the conditions of the TQ resonance and the narrowing effect. Under the
      exact TQ resonance, the ratio of the TQ resonance frequency to the Larmor
      frequency of the RF field depends only on phim, and the secular part of the
      magnetic dipole Hamiltonian of a like spin system in the triply rotating frame
      disappears at a particular value of phim. The condition is different from that of
      the well-known magic angle condition.

PMID- 14643713
TI  - Detection of natural abundance 1H-13C correlations of cholesterol in its membrane
      environment using a gradient enhanced HSQC experiment under high resolution magic
      angle spinning.
AB  - The quality and signal to noise ratio of a J-based HETCOR performed on a standard
      MAS probe have been compared with a gradient enhanced HSQC performed on a HR-MAS
      probe at 500 MHz. The sample selected was cholesterol, inserted at 30 mol% in
      acyl chain deuterated phospholipids (DMPC-d54), at a temperature where the
      bilayer is in a liquid crystalline phase (310 K). It is representative of any
      rigid molecule undergoing fast axial diffusion in a bilayer as the main movement.
      After optimization of the spinning rate and carbon decoupling conditions, it is
      shown that the ge-HSQC/MAS approach is far superior to the more conventional J
      HETCOR/MAS in terms of signal to noise ratio, and that it allows the detection of
      all the natural abundance cross peaks of cholesterol in a membrane environment.
      Clear differences between the 1H and 13C chemical shifts of cholesterol in a
      membrane and in chloroform solution were thus revealed.

PMID- 14643714
TI  - Isolating quantum coherences in structural imaging using intermolecular double
      quantum coherence MRI.
AB  - Intermolecular multiple-quantum coherence (iMQC) MR imaging provides a
      fundamentally different contrast mechanism. It allows probing tissue
      microstructure by tuning the direction and strength of the correlation gradient.
      However, iMQC images of a specific quantum-coherence can easily be contaminated
      by leakage signals from undesired quantum coherences (zero, single, and triple
      quantum coherence in this work). Using a modified double-quantum CRAZED imaging
      sequence, we show that signals originating from various coherence orders (M=0, 1,
      2, 3) can be predicted in k-space and effectively isolated by means of a four
      step phase cycling scheme and judicious choice of flip angles. Finally,
      preliminary data suggest the method to be able to provide information on
      trabecular bone architecture such as regional mean trabecular plate separation.

PMID- 14643715
TI  - High-throughput backbone resonance assignment of small 13C,15N-labeled proteins
      by a triple-resonance experiment with four sequential connectivity pathways using
      chemical shift-dependent, apparent 1J(1H,13C): HNCACBcodedHAHB.
AB  - The proposed three-dimensional triple-resonance experiment HNCACBcodedHAHB
      correlates sequential 15N, 1H moieties via the chemical shifts of 13Calpha,
      13Cbeta, 1Halpha, and 1Hbeta. The four sequential correlation pathways are
      achieved by the incorporation of the concept of chemical shift-coding [J. Biomol.
      NMR 25 (2003) 281] to the TROSY-HNCACB experiment. The monitored 1Halpha and
      1Hbeta chemical shifts are then coded in the line shape of the cross-peaks of
      13Calpha, 13Cbeta along the 13C dimension through an apparent residual scalar
      coupling, the size of which depends on the attached hydrogen chemical shift. The
      information of four sequential correlation pathways enables a rapid backbone
      assignment. The HNCACBcodedHAHB experiment was applied to approximately 85%
      labeled 13C,15N-labeled amino-terminal fragment of Vaccinia virus DNA
      topoisomerase I comprising residues 1-77. After one day of measurement on a
      Bruker Avance 700 MHz spectrometer and 8 h of manual analysis of the spectrum 93%
      of the backbone assignment was achieved.

PMID- 14643716
TI  - Arrayed acquisition of 2D exchange NMR spectra within a single scan experiment.
AB  - We have recently demonstrated that magnetic field gradients in combination with
      frequency selective pulses, can be employed to collect a complete multi
      dimensional NMR spectrum within a single scan. Following similar guidelines,
      field gradients could also be exploited to parallelize other types of NMR
      experiments where the final results arise from the collection and analysis of a
      series of time-incremented spectra. The present Communication exemplifies this
      concept by showing how a combination of gradients can be employed to monitor
      within a single continuous acquisition, a slow dynamic process which is in turn
      followed by systematic increments in the duration of a magnetization transfer
      time. Further, since 2D exchange NMR spectra can nowadays be themselves collected
      within one scan, the acquisition of a complete set of mixing-incremented 2D
      exchange patterns could be achieved within a single experiment entailing a total
      time of approximately 1 s.

PMID- 14643717
TI  - Building nursing knowledge through informatics: from concept representation to
      data mining.

PMID- 14643718
TI  - Methods in informatics: using data derived from a systematic review of health
      care texts to develop a concept map for use in the neonatal intensive care
      setting.
AB  - A qualitative systematic review of textbooks and clinical guidelines identified
      assessment criteria for initiation of nipple feeds in premature infants cared for
      in the neonatal intensive care unit (NICU) setting. Using a structured method for
      text source selection and data extraction, 43 health care texts were
      systematically reviewed yielding 153 separate statements related to assessing
      premature infants' feeding readiness. Following this procedure, a pile sort
      method was conducted wherein an expert neonatal nurse practitioner (NNP) grouped
      the statements according to similarity in meaning. Ten piles of terms emerged
      from this process. Each pile was "named," depicting discrete components used when
      assessing premature infants' readiness for nipple feeding. Using these public
      data and the private knowledge of the NNP informant, a concept map was
      constructed to illustrate a framework for decision support development and to
      examine the map's usefulness for structuring knowledge that will provide input to
      an intelligent decision support system.

PMID- 14643719
TI  - Role and experience determine decision support interface requirements in a
      neonatal intensive care environment.
AB  - The aim of this paper is to describe a novel approach to the analysis of data
      obtained from card-sorting experiments. These experiments were performed as a
      part of the initial phase of a project, called NEONATE. One of the aims of the
      project is to develop decision support tools for the neonatal intensive care
      environment. Physical card-sorts were performed using clinical "action" and
      patient "descriptor" words. Thirty-two staff (eight junior nurses, eight senior
      nurses, eight junior doctors, and eight senior doctors) participated in the
      actions card-sorts and the same number of staff participated in separate
      descriptors card-sorting experiments. To check for consistency, the card-sorts
      were replicated for nurses during the action card-sorts. The card-sort data were
      analysed using hierarchical cluster analysis to produce tree-diagrams or
      dendrograms. Differences were shown in the way various classes of staff with
      different levels of experience mentally map clinical concepts. Clinical actions
      were grouped more loosely by nurses and by those with less experience, with a
      polarisation between senior doctors and junior nurses. Descriptors were classed
      more definitively and similarly by nurses and senior doctors but in a less
      structured way and quite differently by junior doctors. This paper presents a
      summary of the differences in the card-sort data for the various staff
      categories. It is shown that concepts are used differently by various staff
      groups in a neonatal unit and that this may diminish the effectiveness of
      computerised decision aids unless it is explored during their development.

PMID- 14643720
TI  - A term extraction tool for expanding content in the domain of functioning,
      disability, and health: proof of concept.
AB  - Among the challenges in developing terminology systems is providing complete
      content coverage of specialized subject fields. This paper reports on a term
      extraction tool designed for the development and expansion of terminology systems
      concerned with functioning, disability, and health. Content relevant to this
      domain is the emphasis of the foci and targets of many nursing terminologies. We
      extend previously published term extraction algorithms by applying two filters.
      The first filter is based on the raw frequency of the content words in the
      lexical string under consideration. The second filter applies the notion of a
      complete syntactic node to discover relevant noun or verb phrases. While we
      report on a limited corpus (30,607 words comprising 4103 terms from 60 dismissal
      note summaries), the recall, precision, and F-measures we observed are
      encouraging and suggest continued development and testing of the tool is merited.

PMID- 14643721
TI  - Using nurses' natural language entries to build a concept-oriented terminology
      for patients' chief complaints in the emergency department.
AB  - Information about the chief complaint (CC), also known as the patient's reason
      for seeking emergency care, is critical for patient prioritization for treatment
      and determination of patient flow through the emergency department (ED). Triage
      nurses document the CC at the start of the ED visit, and the data are
      increasingly available in electronic form. Despite the clinical and operational
      significance of the CC to the ED, there is no standard CC terminology. We propose
      the construction of concept-oriented nursing terminologies from the actual
      language used by experts. We use text analysis to extract CC concepts from triage
      nurses' natural language entries. Our methodology for building the nursing
      terminology utilizes natural language processing techniques and the Unified
      Medical Language System.

PMID- 14643722
TI  - Evaluation of the draft international standard for a reference terminology model
      for nursing actions.
AB  - PURPOSE: The purpose of this study was to evaluate the draft ISO reference
      terminology model (RTM) for nursing actions. Nursing RTM models attempt to
      include concepts that are universally represented in nursing documentation to
      improve the depiction of nursing practice in computerized systems. METHOD:
      Content analysis was used to decompose interventions into words and phrases,
      which were then mapped to the six model categories used to represent nursing
      actions in the draft ISO RTM. The decomposition of interventions was applied to
      nurses' documentation of pain interventions entered into a clinical information
      system. FINDINGS: Consistent with the ISO standard requirements, all (100.00%) of
      the interventions contained an <action> word or phrase and a <<target>>.
      Additional findings are discussed in relation to earlier studies of terminology
      models. CONCLUSIONS: It is recommended that terminology and information system
      developers consider this model in their ongoing system development, evaluation,
      maintenance, and revisions. Further evaluation of the ISO RTM for nursing will
      contribute to the goals of this specific model and the harmonization and
      integration with other health care models.

PMID- 14643723
TI  - Determining sources for formal nursing terminology systems.
AB  - OBJECTIVE: The purpose of this study is to assess the relative merits of aspects-
      labels or informal definitions--of traditional nursing terminology systems as the
      foundational sources for target formal nursing terminology systems. DESIGN: This
      study builds upon and compares the findings of two previous experiments in which
      formal terminology systems, one based on informal definitions, the other based on
      labels, were developed under the GALEN approach and used to generate hierarchies
      of nursing interventions drawn from the Nursing Interventions Classification.
      MEASUREMENTS: The two generated hierarchies were compared to see whether, and to
      what extent, they captured a test set of hierarchical relationships implicit
      within and derived from the Nursing Interventions Classification. An analysis of
      the relevant conceptual representations was carried out in those cases where a
      hierarchical relationship from the test set was absent from either of the
      generated hierarchies. RESULTS: The hierarchy generated from the formal
      terminology system based on informal definitions contained none of the test set
      of hierarchical relationships. Reasons included structural differences between
      conceptual representations; different levels of specificity; and deficiencies
      within the formal terminology system itself. The hierarchy generated from the
      formal terminology system based on labels contained all but one of the test set.
      The reason for the one absence was inconsistent usage within source and target.
      CONCLUSIONS: While it may be possible to derive formal terminology systems from
      informal definitions for nursing interventions, the inherent complexity within
      those informal definitions brings into question the utility of such systems. This
      study demonstrates that it may be more productive to base formal nursing
      terminology systems on labels, simpler sources with limited discursive content
      and a higher degree of consistency.

PMID- 14643724
TI  - Representing nursing assessments in clinical information systems using the
      logical observation identifiers, names, and codes database.
AB  - In recent years, the Logical Observation Identifiers, Names, and Codes (LOINC)
      Database has been expanded to include assessment items of relevance to nursing
      and in 2002 met the criteria for "recognition" by the American Nurses
      Association. Assessment measures in LOINC include those related to vital signs,
      obstetric measurements, clinical assessment scales, assessments from standardized
      nursing terminologies, and research instruments. In order for LOINC to be of
      greater use in implementing information systems that support nursing practice,
      additional content is needed. Moreover, those implementing systems for nursing
      practice must be aware of the manner in which LOINC codes for assessments can be
      appropriately linked with other aspects of the nursing process such as diagnoses
      and interventions. Such linkages are necessary to document nursing contributions
      to healthcare outcomes within the context of a multidisciplinary care environment
      and to facilitate building of nursing knowledge from clinical practice. The
      purposes of this paper are to provide an overview of the LOINC database, to
      describe examples of assessments of relevance to nursing contained in LOINC, and
      to illustrate linkages of LOINC assessments with other nursing concepts.

PMID- 14643725
TI  - Modeling nursing interventions in the act class of HL7 RIM Version 3.
AB  - The proposed Health Level 7 Reference Information Model (HL7 RIM) Version 3 is
      the foundation for expressing data to be communicated across health care
      information systems. The general objective of this analysis was to examine
      whether the RIM supports the expression of nursing interventions, considering
      both terminological and structural perspectives. The Nursing Terminology Summit
      Interventions Group focused on patient education about breast cancer, an
      intervention that differs sufficiently from other medical processes already
      considered by HL7 and represents issues surrounding both definition and execution
      of nursing process. Relevant actors, actions, and action relationships were
      culled from use cases and modeled into the proposed RIM structure and attributes
      by using modified instance diagrams. This method was effective and reproducible,
      and the RIM proved to be an adequate model for supporting breast cancer
      education. Additional interventions must be studied to fully assess the adequacy
      of the model to support all aspects of nursing process and terminology.

PMID- 14643726
TI  - Development and evaluation of a terminology-based electronic nursing record
      system.
AB  - The present study was conducted to develop and evaluate a terminology-based
      electronic nursing record system. The narrative nursing notes of 63 obstetric
      patients collected over 395 hospital days were decomposed and cross-mapped with
      the Korean version of the beta version of the International Classification for
      Nursing Practice (ICNP). The terminology-based nursing record system was
      developed with a terminology server to manage nursing concepts and nursing
      phrases, and a user application system to document nursing notes. The system was
      evaluated in two Korean hospitals by 20 nurses documenting nursing notes of 57
      patients. Patterns were found in nursing notes reflecting the nursing process. A
      total of 14,727 phrases were used for documenting nursing notes, with these
      phrases consisting of 237 unique phrases. Among the 259 unique nursing concepts
      extracted from the 237 unique phrases, 103 concepts (39.8%) did not map onto the
      ICNP. The users were able to find nursing phrases with a success rate of 89.4%.
      The mean time required for documentation at each input session decreased
      significantly from 276 to 158 s as the users became more experienced.

PMID- 14643727
TI  - Adequacy of evolving national standardized terminologies for interdisciplinary
      coded concepts in an automated clinical pathway.
AB  - PURPOSE: The purpose of this analysis was to determine the adequacy of evolving
      national standardized terminologies with regard to coded data elements (concepts)
      in an automated clinical pathway designed to drive adherence with the American
      College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for
      Evaluation and Management of Chronic Heart Failure. METHOD: Concepts were
      identified in a previously developed automated clinical pathway and associated
      tools. Once identified, concepts were categorized according to the conceptual
      domains identified by Campbell et al. (1997). A review of evolving national
      standardized terminologies and coding systems was initiated to determine if the
      identified concepts had corresponding representation in one of these coding
      systems. Available codes were then evaluated for adequacy with respect to
      national guideline adherence measures put forth by the Centers for
      Medicare/Medicaid Services (CMS) and Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO). RESULTS: The concept domain model put forth by
      Campbell et al. (1997) worked well for organizing concepts and for providing a
      useful framework for data analysis. Using our method, 260 unique pathway concepts
      were identified, of which, 91.9% (239) are represented by one or more of the
      standardized coding systems. Logical Observation Identifiers Names and Codes
      (LOINC) and SNOMED CT alone represented 86.2% of the concepts. Seventy percent
      (70%) of the clinical pathway concepts are represented using the Health Insurance
      Portability and Accountability Act (HIPAA) mandated national terminologies alone.
      Less than 50% of CMS and JCAHO guideline adherence concepts were found to have
      representation in the HIPAA mandated terminologies. The addition of Logical
      Observation Identifier Names and Codes (LOINC) and SNOMED CT improved
      representation up to 86.4%, but did not include representation of all concepts
      necessary for complete electronic monitoring of guideline adherence. CONCLUSIONS:
      Evolving national standardized terminologies provided matching terms for the
      majority of the data elements in the automated clinical pathway. Standard
      clinical terminologies with granular terms such as LOINC and SNOMED CT are
      required to represent the depth and detail of certain procedures and guideline
      based care. Gaps exist in Health Insurance Portability and Accountability Act
      (HIPAA) mandated terminologies for representing interdisciplinary concepts in
      national adherence measures.

PMID- 14643728
TI  - Controlled vocabularies for consumer health.
AB  - There is often a disconnect between the language that consumers use to express
      health concerns and the language that is used by health care professionals. At
      the same time, health care consumerism and the availability of vast health
      related resources on the Internet have resulted in millions of persons using the
      Internet for health-related matters daily. The mismatch in language, however,
      poses a barrier to access to relevant information. It also prevents full
      participation in shared health records, and sometimes interferes in communication
      between patients and their health care providers. Nurse informaticians, with
      their deep expertise in vocabulary development, could play an important role in
      solving this dilemma. Structured vocabularies comprised of lay terms, with
      definitions, variant spellings, and regional dialects, along with mappings to
      equivalent or related professional terms, could make health literature much more
      accessible to consumers, and provide the basis for bi-directional translation of
      health terms in a shared medical record. In addition, the presence of terms for
      which no representation currently exists in nursing terminologies could serve as
      a stimulus for developing new knowledge about patient phenomena not previously
      recognized.

PMID- 14643729
TI  - Towards linking patients and clinical information: detecting UMLS concepts in e
      mail.
AB  - The purpose of this project is to explore the feasibility of detecting terms
      within the electronic messages of patients that could be used to effectively
      search electronic knowledge resources and bring health information resources into
      the hands of patients. Our team is exploring the application of the natural
      language processing (NLP) tools built within the Lister Hill Center at the
      National Library of Medicine (NLM) to the challenge of detecting relevant
      concepts from the Unified Medical Language System (UMLS) within the free text of
      lay people's electronic messages (e-mail). We obtained a sample of electronic
      messages sent by patients participating in a randomized field evaluation of an
      internet-based home care support service to the project nurse, and we subjected
      elements of these messages to a series of analyses using several vocabularies
      from the UMLS Metathesaurus and the selected NLP tools. The nursing vocabularies
      provide an excellent starting point for this exercise because their domain
      encompasses patient's responses to health challenges. In successive runs we
      augmented six nursing vocabularies (NANDA Nursing Diagnosis, Nursing
      Interventions Classification, Nursing Outcomes Classification, Home Health
      Classification, Omaha System, and the Patient Care Data Set) with selected sets
      of clinical terminologies (International Classification of Primary Care;
      International Classification of Primary Care- American English; Micromedex
      DRUGDEX; National Drug Data File; Thesaurus of Psychological Terms; WHO Adverse
      Drug Reaction Terminology) and then additionally with either Medical Subject
      Heading (MeSH) or SNOMED International terms. The best performance was obtained
      when the nursing vocabularies were complemented with selected clinical
      terminologies. These findings have implications not only for facilitating lay
      people's access to electronic knowledge resources but may also be of assistance
      in developing new tools to aid in linking free text (e.g., clinical notes) to
      lexically complex knowledge resources such as those emerging from the Human
      Genome Project.

PMID- 14643730
TI  - Toward national comparable nurse practitioner data: proposed data elements,
      rationale, and methods.
AB  - Federal funds have supported Nurse Practitioner (NP) education and the
      establishment of nurse-managed centers. Yet, important questions are raised about
      the quality and appropriate scope of NP care. Few NP-patient encounters are
      documented in the largest national surveys of ambulatory care, sponsored by the
      National Center for Health Statistics, due to sampling frames that are based on
      physician practices. In addition, these national surveys lack essential outcome
      indicators, therefore limiting their data to descriptions of patient demographics
      and practice patterns. Informatics principles are applied to a proposed expansion
      of the National Ambulatory Medical Care Survey. Its sample would include nurse
      managed centers and its variables would include quality outcome and process
      indicators in standardized language that are nurse-sensitive and that reflect
      national priorities for action on health care quality. Variables for inclusion in
      a draft pilot instrument are identified.

PMID- 14643731
TI  - Using computational modeling to transform nursing data into actionable
      information.
AB  - Transforming organizational research data into actionable information nurses can
      use to improve patient outcomes remains a challenge. Available data are numerous,
      at multiple levels of analysis, and snapshots in time, which makes application
      difficult in a dynamically changing healthcare system. One potential solution is
      computational modeling. We describe our use of OrgAhead, a theoretically based
      computational modeling program developed at Carnegie Mellon University, to
      transform data into actionable nursing information. We calibrated the model by
      using data from 16 actual patient care units to adjust model parameters until
      performance of simulated units ordered in the same way as observed performance of
      the actual units 80% of the time. In future research, we will use OrgAhead to
      generate hypotheses about changes nurses might make to improve patient outcomes,
      help nurses use these hypotheses to identify and implement changes on their
      units, and then measure the impact of those changes on patient outcomes.

PMID- 14643732
TI  - The Nursing Terminology Summit Conferences: a case study of successful
      collaboration for change.
AB  - The Nursing Terminology Summit, a series of invitational conferences and ongoing
      collaboration, has played both initiating and contributing roles to bring about a
      second-order change in the development and integration of standards for nursing
      terminology. What factors enabled this success? What factors made change
      difficult? This paper examines the structure and process of the Nursing
      Terminology Summit using concepts, principles, theories, and strategies
      identified in Lorenzi and Riley [Organizational Aspects of Health Informatics:
      Managing Technological Change, Springer, 1995]. As a case study, this critical
      analysis offers practical lessons for informaticians in managing change across
      disciplinary, organizational, and national boundaries.

PMID- 14643733
TI  - A nursing perspective to design and implementation of electronic patient record
      systems.
AB  - Achievements in informatics and use of new technologies are important to develop
      knowledge from clinical nursing practice. At the same time, progress in design
      and implementation of clinical information systems such as comprehensive
      Electronic Patient Record (EPR) systems can be complemented by attention to and
      examination of information processes as well as the health care constituencies'
      characteristics. In this article, selected issues and challenges related to EPR
      design and implementation are reviewed with a particular emphasis on those
      related to nursing practice and nursing leadership.

PMID- 14643734
TI  - Data mining issues and opportunities for building nursing knowledge.
AB  - Health care information systems tend to capture data for nursing tasks, and have
      little basis in nursing knowledge. Opportunity lies in an important issue where
      the knowledge used by expert nurses (nursing knowledge workers) in caring for
      patients is undervalued in the health care system. The complexity of nursing's
      knowledge base remains poorly articulated and inadequately represented in
      contemporary information systems. There is opportunity for data mining methods to
      assist with discovering important linkages between clinical data, nursing
      interventions, and patient outcomes. Following a brief overview of relevant data
      mining techniques, a preterm risk prediction case study illustrates the
      opportunities and describes typical data mining issues in the nontrivial task of
      building knowledge. Building knowledge in nursing, using data mining or any other
      method, will make progress only if important data that capture expert nurses'
      contributions are available in clinical information systems configurations.

PMID- 14643735
TI  - Bayesian networks for knowledge discovery in large datasets: basics for nurse
      researchers.
AB  - The growth of nursing databases necessitates new approaches to data analyses.
      These databases, which are known to be massive and multidimensional, easily
      exceed the capabilities of both human cognition and traditional analytical
      approaches. One innovative approach, knowledge discovery in large databases
      (KDD), allows investigators to analyze very large data sets more comprehensively
      in an automatic or a semi-automatic manner. Among KDD techniques, Bayesian
      networks, a state-of-the art representation of probabilistic knowledge by a
      graphical diagram, has emerged in recent years as essential for pattern
      recognition and classification in the healthcare field. Unlike some data mining
      techniques, Bayesian networks allow investigators to combine domain knowledge
      with statistical data, enabling nurse researchers to incorporate clinical and
      theoretical knowledge into the process of knowledge discovery in large datasets.
      This tailored discussion presents the basic concepts of Bayesian networks and
      their use as knowledge discovery tools for nurse researchers.

PMID- 14643736
TI  - Marginalization and health geomatics.
AB  - Marginalized groups have been defined as groups that have been peripheralized
      from the center of society. Increasing nursing knowledge of marginalized groups
      and the dynamics of population diversity will enable nurses to better recognize
      shifting health patterns, plan for utilization of health services, and determine
      ethnic and cultural differences that exist in marginalized populations. The
      authors of this article review theoretical models responsible for defining the
      concept marginalization, describe geographical information systems as a
      recommended tool to evaluate marginalized groups, and provide a case study
      utilizing tools and maps as a means of assessing marginal situations.

PMID- 14643737
TI  - Peer and adult relationships of adolescents with disabilities.
AB  - The purpose of this study was to enhance our knowledge of what it is like to grow
      up with a disability, specifically, with focus on how adolescents with restricted
      mobility perceive social roles and relationships to peers and adults. The group
      investigated consisted of 12 adolescents with restricted mobility from northern
      Sweden, aged from 15 to 19 years. The adolescents were individually interviewed.
      The analysis resulted in a core category (Who am I), which describes how the
      adolescents perceive themselves. The core category was related to three
      subcategories: Relationships to friends--describes the adolescents' experiences
      of peer relationships, Relationships to adults--describes adolescents'
      relationships to adults, Thoughts about relationships in the future--comprises
      wishes for future relationships. The results indicated that the 12 disabled
      adolescents saw themselves as regular members of the adolescent peer group but
      that the members of the adolescent group saw them as being different. The
      relationships to friends of the same age were either markedly defective or did
      not exist at all, while relationships to adults were often characterized as
      ambivalent or asymmetric, i.e. the adults were simultaneously helpful and
      supportive while over protective and dominant. The study revealed that despite
      the many hindrances, the adolescents had a comparatively positive view of their
      future.

PMID- 14643738
TI  - Adolescents and their parents' perceptions about parenting characteristics. Who
      can better predict the adolescent's academic competence?
AB  - This study examined family factors reported by parents and their children in
      relation to children's academic competence. Adolescents and their parents (N=323)
      reported about the same family characteristics: parental acceptance and
      involvement in the children's education. Measures related to children's academic
      competence were: academic competence rated by the teacher, self-reported grades,
      perceived academic competence and motivational orientation. The results revealed
      low interrater agreement in family measures. Moreover, ratings by children about
      parenting characteristics seem higher than those of their parents in predicting
      academic-related measures. This was true especially in the case of children's
      reports on acceptance. However, in the case of involvement, parent's reports
      contributed towards predicting a higher number of variables.

PMID- 14643739
TI  - Young male prisoners in a Young Offenders' Institution: their contact with
      suicidal behaviour by others.
AB  - Prison suicide rates are increasing. The impact of witnessing a suicide or how
      many people do so is unknown. The aim of this study was to find how many young
      people detained in a Young Offenders' Institution (YOI) have had contact with
      another's suicide attempt and to test for association between this and own self
      harming behaviour. A questionnaire, developed for the project, was distributed
      within a YOI. 74% (355/480) responded. One hundred and fifty-one (43%) of the
      young men reported that they knew someone who had attempted suicide, 48 of them
      knowing someone who had thereby died. The contact with a non-fatal suicide
      attempted by others was associated with own self-harm (OR 1.73, CI 1.39-21.4,
      p<0.01); contact with completed suicide had no such association. The most
      important factor that increased the chance of knowing a suicide attempter was
      actual length of time spent in prison up to the time of the study; 95 (63%) of
      the young men with such contact had it in prison. No other significant
      vulnerability factors were identified. It seems likely that imprisonment is a
      specific vulnerability factor for self-harm, one explanation being that it
      increases the risk of exposure to a contact with suicidal behaviour by others.
      Further work is called for to test relationships between such exposure and own
      behaviour over time, and to gather first hand accounts from the young men in such
      circumstances in order to understand the meaning for them of the contact with
      suicidal behaviour by others. This would inform appropriate intervention
      strategies, and could save much morbidity, and even mortality.

PMID- 14643740
TI  - Motivation and self-perception profiles and links with physical activity in
      adolescent girls.
AB  - Research shows a decline in participation in physical activity across the teenage
      years. It is important, therefore, to examine factors that might influence
      adolescent girl's likelihood of being physically active. This study used
      contemporary theoretical perspectives from psychology to assess a comprehensive
      profile of motivational and self-perception variables in 11-16 year old English
      girls (n=516). A cross-sectional design was employed. Cluster analysis was
      conducted to (a) map cluster profiles and (b) test whether clusters differed in
      physical self-worth, global self-esteem, and physical activity. Results revealed
      a five-cluster solution depicting 40% of the sample as moderately motivated, 30%
      lowly motivated in two clusters, and 30% highly motivated, also in two clusters.
      However, differences between clusters on physical activity were quite small.
      Results show potential areas for intervention to enhance the motivation of
      adolescent girls for physical activity.

PMID- 14643741
TI  - Direct and vicarious victimization at school and at home as risk factors for
      suicidal cognition among Italian adolescents.
AB  - Suicidal cognition is defined here as the combination of thinking about
      committing suicide and engaging in self-harm and is considered to indicate
      maladjustment following an extreme internalized reaction to negative life events.
      Victimization at home and at school might lead some youth to suicidal cognition.
      The present study aimed to examine cross-sectional predictors of suicidal
      cognition focusing on the unique influence of 'direct victimization' at school by
      peers and at home by parents, over and above that of vicarious victimization
      (i.e. exposure to domestic violence). Participants were 998 adolescents randomly
      recruited from high schools in Italy who had to fill in a cross-sectional survey
      measuring different dimensions associated with suicidal cognition. Thoughts about
      committing suicide and self-harming in the previous 6 months were reported by
      almost a fourth of the whole sample, with girls having these thoughts more
      frequently than boys. A high prevalence rate was reported also for direct
      victimization at school (over half of the sample), and at home (a third of the
      sample) and for vicarious victimization at home (reported by a fifth of the
      entire sample). Multiple hierarchical regressions showed that a significant
      proportion of the total variance of suicidal cognition was explained by gender
      and age, meaning that older girls are more at risk of suicidal cognition than
      boys; relational victimization at school is also a risk factor. Direct
      victimization at home by the father for boys and by the father and the mother for
      girls significantly predicted suicidal cognition after controlling for exposure
      to domestic violence.

PMID- 14643742
TI  - Testing direct and indirect effects of sports participation on perceived health
      in Spanish adolescents between 15 and 18 years of age.
AB  - This paper examines the direct and indirect effects of sports participation on
      perceived health. It is based on a representative sample of middle adolescents
      aged 15-18 (N=1038, M age=16.31, S.D.=0.92; 510 boys and 528 girls) from the
      Valencian Community (Spain). This study used two different models; Model A is an
      adaptation of Thorlindsson, Vilhjalmsson and Valgeirsson's (Social Science and
      Medicine 31 (1990) 551) model which introduces smoking, alcohol use, feelings of
      anxiety, feelings of depression and psychophysiological symptoms as mediator
      variables; Model B is an extension of Model A with perceived physical fitness as
      an added mediator variable. Both models show a good fit to the data. Results
      showed that, in both models, sports participation affected perceived health
      directly and indirectly by decreasing smoking and alcohol consumption, feelings
      of depression and psychophysiological symptoms. In Model B, sport also affected
      perceived health via increased perceived physical fitness explaining almost 10%
      more of the variance.

PMID- 14643743
TI  - Adolescent religiosity and sexuality: an investigation of reciprocal influences.
AB  - The present study examined potential bi-directional associations between
      religiosity and first sexual intercourse. The sample, drawn from the National
      Longitudinal Survey of Youth, included 303 teens (22% Hispanic, 35% Black, 43%
      White; 53% male) aged 15-16 in 1996 and 17-18 in 1998. All teens included in the
      sample were virgins at Time 1. In the longitudinal analyses, higher Time 1
      religiosity (a composite of importance of religion and frequency of church
      attendance) was associated with a lower likelihood of first sexual intercourse
      between Time 1 and Time 2. However, transition to sexual activity between Time 1
      and Time 2 was not significantly related to Time 2 religiosity. Thus, results do
      not support a bi-directional association; instead, it appears that teens with
      higher levels of religiosity tend to delay sexual involvement more than those
      with lower levels of religiosity.

PMID- 14643744
TI  - Associations among sexual attraction status, school belonging, and alcohol and
      marijuana use in rural high school students.
AB  - Analysis of data collected from 1725 9th graders from 25 rural high schools
      revealed that students reporting same-sex attraction or uncertainty about their
      attraction status also reported significantly lower GPAs, lower school belonging,
      and higher marijuana and alcohol use. Regression analyses confirmed that beyond
      the effects of GPA and biological sex, sexual minority attraction status was
      negatively associated with school belonging. Further, while higher school
      belonging significantly decreased the odds of alcohol and marijuana use, sexual
      attraction status did not significantly contribute to the model. Post-hoc
      analyses indicated that sexual minority students systematically reported that
      they perceived less privacy in completing the survey, lending support to the
      notion that these adolescents may feel less trusting of their school
      environments. These findings are discussed in light of the need for interventions
      to address the developmental challenges of sexual minority students.

PMID- 14643745
TI  - Trajectories of delinquent behaviour in adolescence and their covariates:
      relations with initial and time-averaged factors.
AB  - This longitudinal study examined individual, family, and peer covariates of
      distinctive trajectories of juvenile delinquency, using data from a community
      sample of 318 German adolescents (mean age at the first wave was 11.45 years).
      Latent growth mixture modelling analysis revealed four trajectory groups: high
      level offenders, medium-level offenders, low-level offenders, and rare offenders.
      The trajectory groups were discriminated better by time-averaged covariates than
      by initial status covariates. High peer tolerance of deviance and low parental
      empathy were consistently linked to varying offending trajectories, whereas
      gender, low academic achievement, and low parental monitoring appeared to be
      trajectory-specific covariates.

PMID- 14643746
TI  - Chronic nicotine causes functional upregulation of ionotropic glutamate receptors
      mediating hippocampal noradrenaline and striatal dopamine release.
AB  - It has been proposed that (-)-nicotine can activate release-stimulating
      presynaptic nicotinic acetylcholine receptors (nAChRs) on glutamatergic nerve
      terminals to release glutamate, which in turn stimulates the release of
      noradrenaline (NA) and dopamine (DA) via presynaptic ionotropic glutamate
      receptors on catecholaminergic terminals. The objective of this study was to
      compare the function of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5
      methylisoxazide-4-propionic acid (AMPA) glutamate receptors in synaptosomes of
      rat hippocampus and striatum following acute and chronic (-)-nicotine
      administration. In hippocampal synaptosomes, prelabeled with [3H]NA, both the
      NMDA- and AMPA-evoked releases were higher in (-)-nicotine-treated (10 days) than
      in (-)-nicotine-treated (1 day) or vehicle-treated (1 or 10 days) rats. In
      striatal synaptosomes prelabeled with [3H]DA, the NMDA-evoked, but not the AMPA
      evoked, release of [3H]DA was higher in (-)-nicotine-treated (10 days) than in
      nicotine-treated (1 day) or vehicle-treated (1 or 10 days) animals. Chronic (-)
      nicotine did not affect catecholamine uptake, basal release and release evoked by
      high-K+ depolarization. Thus, chronic exposure to nicotine enhances the function
      of ionotropic glutamate receptors mediating noradrenaline release in the
      hippocampus and dopamine release in the striatum.

PMID- 14643747
TI  - Involvement of membrane GABA transporter in alpha-latrotoxin-stimulated [3H]GABA
      release.
AB  - Alpha-latrotoxin evokes massive [3H]GABA release from rat brain synaptosomes by
      stimulating exocytosis and outflow from non-vesicular pool. In the present study,
      GABA transporter-mediated [3H]GABA release was shown to be involved in alpha
      latrotoxin-triggered release of [3H]GABA from non-vesicular pool. The following
      agents have been exploited as tools: (1) a protonophore carbonyl cyanide-p
      trifluoromethoxyphenyl-hydrazon (FCCP) and bafilomycin A1 for evoking depletion
      of synaptic vesicle [3H]GABA and enlargement of non-vesicular pool; (2) a non
      substrate high-affinity GABA transport blocker NO-711 for determining
      participation of GABA carrier in the toxin-stimulated GABA release; (3) a
      competitive inhibitor of GABA reuptake nipecotic acid for heteroexchange [3H]GABA
      release. As shown by the experiments with nipecotic acid, FCCP and bafilomycin A1
      considerably increase the content of non-vesicular [3H]GABA. The treatment of the
      synaptosomes with these agents modified the response to alpha-latrotoxin,
      particularly to its subnanomolar concentrations: the lack or substantial lowering
      of the toxin-evoked release during the first 2 min after the toxin addition and
      substantial enhancement of release up to the 5th minute were observed. Only the
      step of enhanced release was sensitive to GABA transporter blocker NO-711.
      Distinct sensitivity to NO-711 was shown to be characteristic for different steps
      of alpha-latrotoxin-stimulated [3H]GABA release from the control, untreated
      synaptosomes: lack of any effect of NO-711 during the first 2 min and powerful
      inhibition in 10 min after the toxin application. Taken together these data
      appear to indicate that the toxin non-simultaneously from vesicular and non
      vesicular origins releases the neurotransmitter, the first rapid step reflects
      exocytosis stimulation, and the second tardy step is at least in part due to the
      release mediated by GABA transporters. The incomplete inhibition with NO-711 of
      the tardy step of the release evoked by nanomolar toxin concentrations suggests
      the participation not only of the GABA transporters.

PMID- 14643748
TI  - Mutant presenilin (A260V) affects Rab8 in PC12D cell.
AB  - Most familial early-onset Alzheimer's disease (FAD) is caused by mutations in the
      presenilin-1 (PS1) gene. Abeta is derived from amyloid precursor protein (APP)
      and an increased concentration of Abeta 42 is widely believed to be a
      pathological hallmark of abnormal PS function. Therefore, the interaction between
      PS1 and APP is a central theme in attempts to clarify the molecular mechanism of
      AD. To examine the effect of PS1 mutations on APP metabolism, we made PC12D cell
      lines that express human PS1 or mutant PS1 (A260V). In PC12D cells expressing the
      PS1A260V mutant, we found that Rab8, a GTPase involved in transport from the
      trans-Golgi network (TGN) to the plasma membrane (PM), was significantly reduced
      in PC12D cells expressing the A260V mutant and that APP C-terminal fragment
      (CTF), the direct precursor of Abeta, accumulated in the heavy membrane fraction
      including membrane vesicles involved in TGN-to-PM transport. Furthermore, the
      total intracellular Abeta production was reduced in these cells. Combined
      together, we have observed that PS1 mutation disturbs membrane vesicle transport,
      resulting in prolonged residence of APP CTF during TGN-to-PM transport pathway.
      Therefore, it is highly likely that reduction of Abeta is closely related to the
      retention of APP CTF during TGN-to-PM transport.

PMID- 14643749
TI  - Crocin prevents the death of PC-12 cells through sphingomyelinase-ceramide
      signaling by increasing glutathione synthesis.
AB  - Crocin is a pharmacologically active component of Crocus sativus L. (saffron)
      that has been used in traditional Chinese medicine. In a previous study, we
      demonstrated that crocin inhibits apoptosis in PC-12 cells by affecting the
      function of tumor necrosis factor-alpha. In this study, we found that depriving
      cultured PC-12 cells of serum/glucose causes a rapid increase in cellular
      ceramide levels, followed by an increase in the phosphorylation of c-jun kinase
      (JNK). The accumulation of ceramide was found to depend on the activation of
      magnesium-dependent neutral sphingomyelinase (N-SMase), but not on de novo
      synthesis. The serum/glucose-deprived PC-12 cells also decreased the cellular
      levels of glutathione (GSH), which is the potent inhibitor of N-SMase. Treating
      the PC-12 cells with crocin prevented N-SMase activation, ceramide production,
      and JNK phosphorylation. We also found that the chemical can enhance the
      activities of GSH reductase and gamma-glutamylcysteinyl synthase (gamma-GCS),
      contributing to a stable GSH supply that blocks the activation of N-SMase. Thus
      our data suggest that crocin combats the serum/glucose deprivation-induced
      ceramide formation in PC-12 cells by increasing GSH levels and prevents the
      activation of JNK pathway, which is reported to have a role of the signaling
      cascade downstream ceramide for neuronal cell death.

PMID- 14643750
TI  - Stimulation of myelin proteolipid protein gene expression by eicosapentaenoic
      acid in C6 glioma cells.
AB  - In this study, the role of exogenous fatty acids in the regulation of proteolipid
      protein (PLP) gene expression was investigated using the following model culture
      system: C6 glioma cells expressing the green-fluorescent protein (eGFP) driven by
      different segments of PLP promoter. Eicosapentanoic acid (EPA; 20:5 n-3), but not
      arachidonic acid (AA; 20:4 n-6), induced a significant increase in medium
      fluorescence intensity (MFI) determined by fluorescence-activated cell sorting
      (FACS). The induction of PLP promoter was time-dependent showing maximal activity
      between 24 and 48 h after EPA exposure. PLP promoter activation was dependent on
      fatty acid concentration, with maximum activation at 200 microM. Northern blot
      analysis confirmed the fluorescence data in C6 cells incubated with EPA.
      Furthermore, this treatment increased the adenylyl cyclase-cyclic AMP (cAMP)
      levels and the mitogen-activated protein kinase (MAPK) activation in C6 cells.
      PLP promoter activity was inhibited by pre-treatment with H89 (protein kinase A
      (PKA) inhibitor), but not with PD98059 (MAPK inhibitor), suggesting that EPA
      stimulates the expression of PLP via cAMP-mediated pathways.

PMID- 14643751
TI  - Alternate splice variants of mouse NR2B gene.
AB  - Two alternate spliced transcripts of N-methyl-D-aspartate receptor (NR2B) gene
      derived from a common promoter have been reported earlier. In the present study,
      we have examined the expression of alternative splice variants of NR2B gene using
      5' rapid amplification of C terminal end (RACE) in the RNA derived from mouse
      cortex. RT-PCR was performed to confirm the RACE data. Here we report the
      occurrence of three transcripts containing a novel alternate spliced exon, we
      refer to as exon 1'. This new exon is located upstream of the transcription start
      site identified by Klein et al. [Gene 208 (1998) 259] in the 5' untranslated
      region (UTR) of NR2B, thus making a new alternate 5' end of the NR2B transcript.
      The molecular nature of the transcripts containing the new exon appears to be
      highly heterogeneous. These results are interesting in that they are of potential
      importance in translational regulation of the NR2B gene.

PMID- 14643752
TI  - 3-hydroxyglutaric acid enhances glutamate uptake into astrocytes from cerebral
      cortex of young rats.
AB  - A predominantly neurological presentation is common in patients with glutaric
      acidemia type I (GA-I). 3-hydroxyglutaric acid (3-OHGA), which accumulates in
      affected patients, has recently been demonstrated to play a central role in the
      neuropathogenesis of this disease. In the present study, we investigated the in
      vitro effects of 3-OHGA at concentrations ranging from 10 to 1000 microM on
      various parameters of the glutamatergic system, such as the basal and potassium
      induced release of [3H]glutamate by synaptosomes, as well as on Na+-dependent
      [3H]glutamate uptake by synaptosomes and astrocytes and Na+-independent
      [3H]glutamate uptake by synaptic vesicles from cerebral cortex of 30-day-old
      Wistar rats. First, we observed that exposure of cultured astrocytes to 3-OHGA
      for 20 h did not reduce their viability. Furthermore, 3-OHGA significantly
      increased Na+-dependent [3H]glutamate uptake by astrocytes by up to 80% in a dose
      dependent manner at doses as low as 30 microM. This effect was not dependent on
      the presence of the metabolite during the uptake assay, since it occurred even
      when 3-OHGA was withdrawn from the medium after cultured cells had been exposed
      to the acid for approximately 1 h. All other parameters investigated were not
      influenced by this organic acid, indicating a selective action of 3-OHGA on
      astrocyte transporters. Although the exact mechanisms involved in 3-OHGA
      stimulatory effect on astrocyte glutamate uptake are unknown, the present
      findings contribute to the understanding of the pathophysiology of GA-I,
      suggesting that astrocytes may protect neurons against excitotoxic damage caused
      by 3-OHGA by increasing glutamate uptake and therefore reducing the concentration
      of this excitatory neurotransmitter in the synaptic cleft.

PMID- 14643753
TI  - Acetaminophen and aspirin inhibit superoxide anion generation and lipid
      peroxidation, and protect against 1-methyl-4-phenyl pyridinium-induced
      dopaminergic neurotoxicity in rats.
AB  - We assessed the antioxidant activity of non-narcotic analgesics, acetaminophen
      and aspirin in rat brain homogenates and neuroprotective effects in vivo in rats
      intranigrally treated with 1-methyl-4-phenyl pyridinium (MPP+). Both drugs
      inhibited cyanide-induced superoxide anion generation, as well as lipid
      peroxidation in rat brain homogenates, the combination of the agents resulting in
      a potentiation of this effect. Acetaminophen or aspirin when administered alone
      or in combination, did not alter dopamine (DA) levels in the forebrain or in the
      striatum. Intranigral infusion of MPP+ in rats caused severe depletion of
      striatal DA levels in the ipsilateral striatum in rats by the third day. Systemic
      post-treatment of acetaminophen afforded partial protection, whereas similar
      treatment of aspirin resulted in complete blockade of MPP+-induced striatal DA
      depletion. While these findings suggest usefulness of non-narcotic analgesics in
      neuroprotective therapy in neurodegenerative diseases, aspirin appears to be a
      potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's
      disease.

PMID- 14643754
TI  - Glutamate-induced differential mitochondrial response in young and adult rats.
AB  - Excitatory amino acid glutamate is involved in neurotransmission in the nervous
      system but it becomes a potent neurotoxin under variety of conditions. However,
      the molecular mechanism of excitotoxicity is not known completely. We have
      studied the influence of glutamate on intracellular calcium and mitochondrial
      functions in cortical slices from young and adult rats. The slices from both the
      age groups exhibited comparable intracellular calcium changes upon glutamate
      stimulation. Glutamate treatment caused a decrease in adenosine 5'
      diphosphate/adenosine 5'-triphosphate (ADP/ATP) and an increase in nicotinamide
      adenine dinucleotide/nicotinamide adenine dinucleotide reduced form (NAD/NADH)
      ratio in both the age groups but the magnitude and the nature of temporal change
      was different. Glutamate-induced decrease in ATP/ADP and increase in NAD/NADH
      ratio was significantly higher in slices from the adult as compared to the young
      rats. The slices from young rats elicited slightly higher mitochondrial
      depolarization than adult rats. However, the formation of reactive oxygen species
      (ROS) and lactate dehydrogenase (LDH) release were significantly higher in adult
      rats as compared to young rats. Glutamate-induced mitochondrial depolarization,
      ROS formation and LDH release were highly dependent on the presence of Ca(2+) in
      the extracellular medium. The treatment of slices with mitochondrial inhibitors
      rotenone and oligomycin inhibited ROS formation and LDH release substantially.
      Our results suggest that the glutamate-induced increase in intracellular calcium
      is not the only factor responsible for neuronal cell death but the mitochondrial
      functions could be crucial in excitotoxicity.

PMID- 14643755
TI  - Presynaptic kainate receptors modulating glutamatergic transmission in the rat
      hippocampus are inhibited by arachidonic acid.
AB  - Kainate receptors are ionotropic glutamate receptors located postsynaptically,
      mediating frequency-dependent transmission, and presynaptically, modulating
      transmitter release. In contrast to the excitatory postsynaptic kainate
      receptors, presynaptic kainate receptor can also be inhibitory and their effects
      may involve a metabotropic action. Arachidonic acid (AA) modulates most
      ionotropic receptors, in particular postsynaptic kainate receptor-mediated
      currents. To further explore differences between pre- and postsynaptic kainate
      receptors, we tested if presynaptic kainate receptors are affected by AA. Kainate
      (0.3-3 microM) and the kainate receptor agonist, domoate (60-300 nM), inhibited
      by 19-54% the field excitatory postsynaptic potential (fEPSP) slope in rat CA1
      hippocampus, and increased by 12-32% paired-pulse facilitation (PPF). AA (10
      microM) attenuated by 37-72% and by 62-66% the domoate (60-300 nM)-induced fEPSP
      inhibition and paired-pulse facilitation increase, respectively. This inhibition
      by AA was unaffected by cyclo- and lipo-oxygenase inhibitors, indomethacin (20
      microM) and nordihydroguaiaretic acid (NDGA, 50 microM) or by the free radical
      scavenger, N-acetyl-L-cysteine (0.5 mM). The K+ (20 mM)-evoked release of
      [3H]glutamate from superfused hippocampal synaptosomes was inhibited by 18-39% by
      domoate (1-10 microM), an effect attenuated by 35-63% by AA (10 microM). Finally,
      the KD (40-55 nM) of the kainate receptor agonist [3H]-(2S,4R)-4-methylglutamate
      ([3H]MGA) (0.3-120 nM) binding to hippocampal synaptosomal membranes was
      increased by 151-329% by AA (1-10 microM). These results indicate that AA
      directly inhibits presynaptic kainate receptor controlling glutamate release in
      the CA1 area of the rat hippocampus.

PMID- 14643756
TI  - Early neutrophilic expression of vascular endothelial growth factor after
      traumatic brain injury.
AB  - The formation of edema after traumatic brain injury (TBI) is in part associated
      with the disruption of the blood-brain barrier. However, the molecular and
      cellular mechanisms underlying these phenomena have not been fully understood.
      One possible factor involved in edema formation is vascular endothelial growth
      factor (VEGF). This growth factor has previously been demonstrated to increase
      the blood-brain barrier permeability to the low molecular weight markers and
      macromolecules. In this study, we analyzed the temporal changes in VEGF
      expression after TBI in rats. In the intact brain, VEGF was expressed at
      relatively low levels and was found in the cells located close to the
      cerebrospinal fluid space. These were the astrocytes located under the ependyma
      and the pia-glial lining, as well as the epithelial cells of the choroid plexus.
      In addition, several groups of neurons, including those located in the
      frontoparietal cortex and in all hippocampal regions, were VEGF-positive. The
      pattern of VEGF-immunopositive staining of neurons and choroidal epithelium
      suggested that in these cells, VEGF binds to the cell membrane-associated heparan
      sulfate proteoglycans. Following TBI, there was an early (within 4 h post-injury)
      increase in VEGF expression in the traumatized parenchyma associated with
      neutrophilic invasion. The ipsilateral choroid plexus appeared to play a role in
      facilitating the migration of neutrophils from blood into the cerebrospinal fluid
      space, from where many of these cells infiltrated the brain parenchyma. VEGF
      immunopositive staining of neutrophils resembled haloes and was found
      ipsilaterally within the frontoparietal cortex and around the velum interpositum,
      a part of the subarachnoid space. These haloes likely represent the deposition of
      neutrophil-derived VEGF within the extracellular matrix, from where this growth
      factor may be gradually released during an early post-traumatic period. The
      maximum number of VEGF-secreting neutrophils was observed between 8 h and 1 day
      after TBI. In addition, from 4 h post-TBI, there was a progressive increase in
      the number of VEGF-immunoreactive astrocytes in the ipsilateral frontoparietal
      cortex. The maximum number of astrocytes expressing VEGF was observed 4 days
      after TBI, and then the levels of astroglial VEGF expression declined gradually.
      Early invasion of brain parenchyma by VEGF-secreting neutrophils together with a
      delayed increase in astrocytic synthesis of this growth factor correlate with the
      biphasic opening of the blood-brain barrier and formation of edema previously
      observed after TBI. Therefore, these findings suggest that VEGF plays an
      important role in promoting the formation of post-traumatic brain edema.

PMID- 14643757
TI  - Heterogeneous expression of the cholecystokinin-like immunoreactivity in the
      mouse hippocampus, with special reference to the dorsoventral difference.
AB  - The neuropeptide cholecystokinin (CCK) is widely distributed in the CNS. We
      herein investigated the immunocytochemical localization of CCK in the
      glutamatergic excitatory pathways in the mouse hippocampus, with particular
      reference to the dorsoventral difference. The intense CCK-like immunoreactivity
      (CCK-LI) was found in the mossy fiber pathway (stratum lucidum and dentate hilus)
      and in the inner molecular layer of the dentate gyrus. In the mossy fiber
      pathway, the CCK-LI was more intense at the ventral level than at the dorsal
      level. On the other hand, the CCK-LI in the stratum lucidum was more intense in
      the distal portion than in the proximal portion, both at the dorsal and ventral
      levels. High-resolution three-dimensional image analysis revealed the
      coexpression of CCK and synaptoporin (SPO) in the single mossy terminal, where
      they were spatially segregated but adjacent to each other. Quantitative image
      analysis indicated the difference in the amount of CCK within the mossy terminals
      along the dorsoventral and transverse axes of the hippocampus. On the other hand,
      in the inner molecular layer, CCK- and SPO-positive elements appeared to have
      little relation to each other. We also examined the postnatal development of the
      CCK-LI in the mouse hippocampus. The CCK-LI was detected in the inner molecular
      layer of the ventral dentate gyrus at postnatal day (P) 7. In the mossy fiber
      pathway, the CCK-LI was first evident at P 14, but it was restricted to the
      distal portion of the stratum lucidum in the ventral hippocampus. Interestingly,
      the distributions of the SPO immunoreactivity at P 7 were already similar to
      those of adult mice. The patterns of expression of CCK-LI at P 28 were almost
      similar to those of adult mice. The present data demonstrate the heterogeneous
      expression of CCK-LI in the mouse hippocampus, and provide a baseline to
      understand the role of CCK in the mouse brain.

PMID- 14643758
TI  - S-allyl-L-cysteine selectively protects cultured rat hippocampal neurons from
      amyloid beta-protein- and tunicamycin-induced neuronal death.
AB  - S-allyl-L-cysteine (SAC), one of the organosulfur compounds found in aged garlic
      extract, has been shown to possess various biological effects including
      neurotrophic activity. In our previous experiments, we found that SAC could
      protect against amyloid beta-protein (Abeta)- and tunicamycin-induced cell death
      in differentiated PC12 cells. In the study described here, we characterized the
      neuronal death induced by Abeta, 4-hydroxynonenal (HNE), tunicamycin, and trophic
      factor deprivation, and investigated whether and how SAC could prevent this in
      cultured rat hippocampal neurons. Treatment with SAC protected these cells
      against Abeta- and tunicamycin-induced neuronal death, which is mediated
      predominantly through caspase-12-dependent pathway in a concentration-dependent
      manner. In contrast, it afforded no protection against HNE- and trophic factor
      deprivation-induced cell death, which has been shown to be mediated by caspase-3
      dependent pathway. SAC also attenuated the Abeta-induced increase of
      intracellular reactive oxygen species in hippocampal neurons. SAC had no effect
      on Abeta-induced cell death in cultured cerebellar granule neurons, which was
      prevented by a caspase-3 inhibitor. These results suggest that SAC could protect
      against the neuronal cell death that is triggered by ER dysfunction in the
      hippocampus, and that it has no effect on neuronal cell death that is dependent
      upon the caspase-3 mediated pathway.

PMID- 14643759
TI  - Local sensory ganglion ischemia induced by endothelin vasoconstriction:
      vulnerability of diabetic neurons and microvessels.
AB  - In some disorders of the peripheral nervous system, it is relevant to understand
      how sensory neurons respond to selective ganglion ischemia. Sensory dorsal root
      ganglia may be susceptible to ischemic damage and irretrievable neuron loss
      because of their metabolic requirements. In diabetes, heightened sensitivity to
      ischemia associated with elevated endothelin levels might render ganglia
      particularly vulnerable. In this work, we created a model of local sensory
      ganglion ischemia by generating intense local vasoconstriction from applied
      endothelin-1 (ET). In this model, we compared relative vulnerability of L5
      ganglia microvessels and neurons to ET in streptozotocin-induced diabetic rats
      and nondiabetic controls. Diabetic ganglia had reductions in baseline core
      ganglion blood flow (GBF) measured using microelectrode hydrogen clearance
      polarography and ET induced particularly profound declines. Serial GBF
      measurements made using a laser Doppler flowmetry probe also indicated that
      diabetic ganglia exposed to ET had a marked prolongation in its action. Neuron
      perikarya and proximal axon segments were more vulnerable in diabetes. Neurons
      exhibited loss of neurofilament labeling, dissolution of the neurons, replacement
      of neurons with "nests of Nageotte," displacement of nuclei to the periphery of
      perikarya, and nuclear labeling with TUNEL. Both intraganglionic axons and
      downstream sural sensory axons developed evidence of axonal degeneration. Local
      endothelin-induced vasoconstriction of microvessels supplying dorsal root ganglia
      provides a selective model of ischemia. Diabetic vessels and neurons, exposed to
      a greater depth and duration of ischemia from endothelin, are especially
      vulnerable.

PMID- 14643760
TI  - The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A
      serotonin receptors in cortical pyramidal neurons in vitro.
AB  - The 5-HT(2A) serotonin receptor represents an important molecular target for
      atypical antipsychotic drugs and for most hallucinogens. In the mammalian
      cerebral cortex, 5-HT(2A) receptors are enriched in pyramidal neurons, within
      which 5-HT(2A) receptors are preferentially sorted to the apical dendrites. In
      primary cortical cultures, 5-HT(2A) receptors are sorted to dendrites and not
      found in the axons of pyramidal neurons. We identified a sorting motif that
      mediates the preferential targeting of 5-HT(2A) receptors to the dendrites of
      cortical pyramidal neurons in vitro. We constructed green fluorescent protein
      tagged 5-HT(2A) receptors wherein potential sorting motifs were disrupted, and
      subsequently employed either the Semliki Forest virus or calcium phosphate for
      the transient expression of recombinant 5-HT(2A) receptors in cultured cortical
      pyramidal neurons. Using dual-labeling immunofluorescent confocal microscopy, we
      quantified the axonal and dendritic sorting patterns of endogenous and
      recombinant 5-HT(2A) receptors. We discovered that disruption of the PDZ-binding
      domain of the 5-HT(2A) receptor greatly attenuates the dendritic targeting of 5
      HT(2A) receptors without inappropriately sorting 5-HT(2A) receptors to axons. The
      PDZ-binding domain is therefore a necessary signal for the preferential targeting
      of the 5-HT(2A) receptor to the dendritic compartment of cultured cortical
      pyramidal neurons, the first such role ascribed to this protein-protein
      interaction motif of any G protein-coupled receptor.

PMID- 14643761
TI  - Neural mechanisms of cortico-cortical interaction in texture boundary detection:
      a modeling approach.
AB  - Texture information is an elementary feature utilized by the human visual system
      to automatically, or pre-attentively, segment the visual scene. The neural
      substrate underlying human texture processing as well as the basic computational
      mechanisms remains largely unknown up to now. We propose a neural model of
      texture processing which integrates the data obtained by a variety of methods
      into a common computational framework. It consists of a hierarchy of bi
      directionally linked visual areas each containing topographical maps of mutually
      interconnected cells. It builds upon the two key hypotheses that (i). texture
      segmentation is based on boundary detection and that (ii). texture border
      detection is mainly a function of higher visual cortical areas such as V4. This
      model, while attempting to explain the processing of textures, is embedded in a
      more general neural model architecture of the infero-temporal pathway of form
      processing.The model allows to link human performance in texture segmentation
      with model cell activation patterns, in turn permitting to trace back fundamental
      psychophysical results on texture processing to their putative neural origins.
      Most importantly, it enables us to identify and evaluate the functional role of
      feedback connections between cortical areas in the context of texture processing,
      namely the suppression of ambiguous cell activities leading to a sharply
      localized detection of texture boundaries. One of the likely neural origins of
      modulatory effects on V1 cell activation levels, as observed in
      electrophysiological studies using single- and multi-unit recordings, can be
      resolved.

PMID- 14643762
TI  - Cerebellar learning of bio-mechanical functions of extra-ocular muscles: modeling
      by artificial neural networks.
AB  - A control circuit is proposed to model the command of saccadic eye movements. Its
      wiring is deduced from a mathematical constraint, i.e. the necessity, for motor
      orders processing, to compute an approximate inverse function of the bio
      mechanical function of the moving plant, here the bio-mechanics of the eye. This
      wiring is comparable to the anatomy of the cerebellar pathways. A predicting
      element, necessary for inversion and thus for movement accuracy, is modeled by an
      artificial neural network whose structure, deduced from physical constraints
      expressing the mechanics of the eye, is similar to the cell connectivity of the
      cerebellar cortex. Its functioning is set by supervised reinforcement learning,
      according to learning rules aimed at reducing the errors of pointing, and deduced
      from a differential calculation. After each movement, a teaching signal encoding
      the pointing error is distributed to various learning sites, as is, in the
      cerebellum, the signal issued from the inferior olive and conveyed to various
      cell types by the climbing fibers. Results of simulations lead to predict the
      existence of a learning site in the glomeruli. After learning, the model is able
      to accurately simulate saccadic eye movements. It accounts for the function of
      the cerebellar pathways and for the final integrator of the oculomotor system.
      The novelty of this model of movement control is that its structure is entirely
      deduced from mathematical and physical constraints, and is consistent with
      general anatomy, cell connectivity and functioning of the cerebellar pathways.
      Even the learning rules can be deduced from calculation, and they reproduce long
      term depression, the learning process which takes place in the dendritic
      arborization of the Purkinje cells. This approach, based on the laws of
      mathematics and physics, appears thus as an efficient way of understanding signal
      processing in the motor system.

PMID- 14643763
TI  - Interleukin-2 receptors and interleukin-2-mediated signaling in myelin:
      activation of diacylglycerol kinase and phosphatidylinositol 3-kinase.
AB  - Myelin was previously shown to possess neurotransmitter and cytokine receptors
      that trigger well-defined signaling mechanisms within the multilamellar
      structure. The present study reveals the presence of an interleukin-2 (IL-2)
      receptor in isolated mouse CNS myelin that responds to recombinant mouse IL-2 by
      activating diacylglycerol kinase (DAGK) and phosphoinositide 3-kinase (PI3K);
      additional evidence suggests participation by protein tyrosine kinase. Activation
      of myelin DAGK by IL-2 occurred in brain stem tissue mince and was blocked by
      chelerythrin chloride, indicating an essential role for myelin-localized protein
      kinase C. Two inhibitors of PI3K, wortmannin and LY294002, blocked endogenous
      PI3K as well as that enhanced by IL-2. Activation of PI3K by IL-2 was also
      blocked by tyrphostin A25, a selective inhibitor of PTK, suggesting activation of
      the latter by IL-2 is upstream to PI3K activation. This reaction resulted in
      tyrosine phosphorylation of a protein tentatively identified as the p85 subunit
      of PI3K. Developmental changes were noted in that receptor density and signaling
      activity were robust during the period of rapid myelination and declined rapidly
      thereafter.

PMID- 14643764
TI  - GABA(B1a), GABA(B1b) AND GABA(B2) mRNA variants expression in hippocampus
      resected from patients with temporal lobe epilepsy.
AB  - The aim of this study was to investigate the mRNA expression of the two GABA(B1)
      receptor isoforms and the GABA(B2) subunit, in human postmortem control
      hippocampal sections and in sections resected from epilepsy patients using
      quantitative in situ hybridisation autoradiography. Utilising human control
      hippocampal sections it was shown that the oligonucleotides employed were
      specific to the receptor. Hippocampal slices from surgical specimens obtained
      from patients with hippocampal sclerosis and temporal lobe epilepsy were compared
      with neurologically normal postmortem control subjects for neuropathology and
      GABA(B) mRNA expression. Neuronal loss was observed in most of the hippocampal
      subregions, but in the subiculum no significant difference was detected. The
      localisation of GABA(B1a) and GABA(B1b) isoform mRNAs in human control
      hippocampal sections supported and extended earlier studies using the GABA(B1)
      pan probe, which does not distinguish between the two GABA(B1) isoforms.
      Moreover, the GABA(B2) mRNA location confirmed the heterodimerisation of the
      receptor. Thus, although there was an apparent correlation between GABA(B1b) and
      GABA(B2), GABA(B1a) exhibited no such relationship. GABA(B1b) and GABA(B2) showed
      a similar intensity of expression whilst GABA(B1a) displayed a lower
      hybridisation signal. Comparison of the expression of the three mRNAs between
      control and epileptic subjects showed significant decreases or increases in
      different hippocampal subregions.GABA(B) isoforms and subunit mRNA expression per
      remaining neuron was significantly increased in the hilus and dentate gyrus.
      These results demonstrate that altered GABA(B) receptor mRNA expression occurs in
      human TLE; possibly the observed changes may also serve to counteract ongoing
      hyperexcitability.

PMID- 14643765
TI  - Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase
      dependent neuronal actin-reorganization.
AB  - Cell surface glycoconjugates are thought to mediate cell-cell recognition and to
      play roles in neuronal development and functions. We demonstrated here that
      exposure of neuronal cells to nanomolar levels of glyco-chains with an N
      acetylgalactosamine (GalNAc) residue at the non-reducing termini (GalNAc-S) such
      as GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer (GM2) ganglioside, its oligosaccharide
      portion, GalNAcbeta4Galbeta4GlcCer (Gg(3)) Cer,
      GalNAcalpha3GalNAcbeta3Galalpha4Galbeta4GlcCer (Gb(5)) Cer (Forssman hapten) and
      alpha1-4 linked oligomers of GalNAc, induced a rapid and transient activation of
      cAMP-dependent protein kinase (PKA) in subplasmalemma. The treatment was
      accompanied by peripheral actin polymerization and filopodia formation in NG108
      15 cells and primary cultured hippocampal neurons, but not in glial cells. A cAMP
      dependent protein kinase (PKA) selective inhibitor and an adenylate cyclase
      inhibitor blocked both PKA activation and the subsequent filopodia formation. A
      small GTPase cdc42 was a potential downstream target of GalNAc-S-activated PKA.
      These results suggest that extracellular GalNAc-S serve as potential regulators
      of the filopodia formation in neuronal cells by triggering the activation of PKA
      followed by cdc42 up-regulation via a cell surface receptor-like component.
      Filopodia formation induced by GalNAc-S may have a physiological relevance
      because long-term exposure to GalNAc-S enhanced F-actin-rich dendrite generation
      of primary cultured hippocampal neurons, and PKA-dependent dendritic outgrowth
      and branch formation of primary cultured cerebellar Purkinje neurons, in which
      actin isoforms were localized to motile structures in dendrites. These findings
      provide evidence for a novel GalNAc/PKA-signaling cascade in regulating some
      neuronal maturation.

PMID- 14643766
TI  - Chronic morphine treatment and withdrawal induce up-regulation of c-Jun N
      terminal kinase 3 gene expression in rat brain.
AB  - Chronic opiate applications produce long-term impacts on many functions of the
      brain and induce tolerance, dependence, and addiction. It has been demonstrated
      that opioid drugs are capable to induce apoptosis of neuronal cells, but the
      mechanism is not clear. c-Jun N-terminal kinase 3 (JNK3), specifically expressed
      in brain, has been proved to mediate neuronal apoptosis and is involved in opiate
      induced cell apoptosis in vitro. The present study investigated the effect of
      opioid administration on expression of JNK3, an important mediator involved in
      apoptosis of neurons, in rat brain. Our results showed that single or chronic
      injection of morphine resulted in a 45-50% increase in the level of JNK3 mRNA in
      frontal cortex, while no significant change was detected in other brain regions
      such as thalamus, hippocampus and locus coeruleus. Similar to what was observed
      after the acute or chronic morphine administration, no significant change in JNK3
      expression was detected in locus coeruleus following cessation of the chronic
      morphine administration. However, interestingly, sustained elevation of JNK3
      expression peaked on day 14 after cessation of morphine treatment was observed in
      the brain regions such as hippocampus and thalamus, where acute or chronic
      morphine treatment did not cause any significant change in JNK3 gene expression.
      The increased JNK3 mRNA in these brain areas returned to the control levels in 28
      days following cessation of chronic morphine treatment. Taken together, these
      results demonstrated for the first time that the expression of JNK3 gene is
      regulated by opioids and that chronic opioid administration and withdrawal could
      induce sustained elevation of JNK3 mRNA in many important brain areas. The
      changes in JNK3 gene expression in brain induced by chronic opioid treatment may
      play a role in opioid-induced apoptosis and neurotoxicity.

PMID- 14643767
TI  - Modulation of action potential firing by iberiotoxin and NS1619 in rat dorsal
      root ganglion neurons.
AB  - The present study investigated the effects of iberiotoxin (IbTx), a peptide toxin
      blocker of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and NS1619,
      a BK(Ca) channel opener, on action potential firing of small and medium size
      afferent neurons from L6 and S1 dorsal root ganglia of adult rats. Application of
      IbTx (100 nM) reduced whole-cell outward currents in 67% of small and medium size
      neurons. Analysis of action potential profile revealed that IbTx significantly
      prolonged the duration of action potential and increased firing frequency of
      afferent neurons. IbTx did not significantly alter the resting membrane
      potential, threshold for action potential activation and action potential
      amplitude. The benzimidazolone NS1619 (10 microM) increased opening activity of a
      Ca(2+)-dependent channel as assessed by single channel measurements. In contrast
      to IbTx, NS1619 reversibly suppressed action potential firing, attributable to
      increases in threshold for evoking action potential, reduction in action
      potential amplitude and increases in amplitude of afterhyperpolarization. The
      effect of NS1619 on neuronal firing was sensitive to IbTx, indicating the
      attenuation of neuronal firing by NS1619 was mediated by opening BK(Ca) channels.
      NS1619 also reduced neuronal hyperexcitability evoked by 4-aminopyridine (4-AP),
      a transient-inactivated K(+) channel (A-current) blocker, in an IbTx-sensitive
      manner. These results indicate that IbTx-sensitive BK(Ca) channels exist in both
      small and medium diameter dorsal root ganglion (DRG) neurons and play important
      roles in the repolarization of action potential and firing frequency. NS1619
      modulates action potential firing and suppresses 4-AP-evoked hyperexcitability in
      DRG neurons, in part, by opening BK(Ca) channels. These results suggest that
      opening BK(Ca) channels might be sufficient to suppress hyperexcitability of
      afferent neurons as those evoked by stimulants or by disease states.

PMID- 14643769
TI  - Involvement of ras activation in toxic hair cell damage of the mammalian cochlea.
AB  - To identify possible intracellular mediators of hair cell (HC) death due to
      ototoxins, we treated basal-turn, neonatal, rat HCs in vitro with several
      intracellular signaling inhibitors, prior to and during gentamicin exposure. The
      general guanine nucleotide-binding protein (G-protein) inhibitor, GDP-betaS (1
      mM), provided potent HC protection, suggesting involvement of G-proteins in the
      intracellular pathway linking gentamicin exposure to HC death. ADP-betaS had
      minimal effect, indicating that the protection is specific to guanosine
      diphosphate (GDP)-binding, rather than a general reaction to nucleotides. Azido
      GTP(32) photolabeling and gel electrophoresis indicated activation of an
      approximately 21 kDa G-protein in HCs after exposure to gentamicin. Spectroscopic
      analysis of peptide fragments from this band matched its sequence with H-Ras. The
      Ras inhibitors B581 (50 microM) and FTI-277 (10 microM) provided potent
      protection against damage and reduced c-Jun activation in HC nuclei, suggesting
      that activation of Ras is functionally involved in damage to these cells due to
      gentamicin.

PMID- 14643770
TI  - Pharmacological characterization of ionotropic glutamate receptors in the
      zebrafish olfactory bulb.
AB  - The distribution of N-methyl-D-aspartate- (NMDA) and kainic acid- (KA) sensitive
      ionotropic glutamate receptors (iGluR) in the zebrafish olfactory bulb was
      assessed using an activity-dependent labeling method. Olfactory bulbs were
      incubated with an ion channel permeant probe, agmatine (AGB), and iGluR agonists
      in vitro, and the labeled neurons containing AGB were visualized
      immunocytochemically. Preparations exposed to 250 microM KA in the presence of a
      NMDA receptor antagonist (D-2-amino-5-phosphono-valeric acid) and an alpha-amino
      3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist (sym
      2206), revealed KA receptor-mediated labeling of approximately 60-70% of mitral
      cells, juxtaglomerular cells, tyrosine hydroxylase-positive cells and granule
      cells. A higher proportion of ventral olfactory bulb neurons were KA-sensitive.
      Application of 333 microM NMDA in the presence of an AMPA/KA receptor antagonist
      (6-cyano-7-nitroquinoxaline-2,3-dione) resulted in NMDA receptor-mediated
      labeling of almost all neurons. The concentrations eliciting 50% of the maximal
      response (effective concentration: EC(50)s) for NMDA-stimulated labeling of
      different cell types were not significantly different and ranged from 148 microM
      to 162 microM. These results suggest that while NMDA receptors with similar
      binding affinities are widely distributed in the neurons of the zebrafish
      olfactory bulb, KA receptors are heterogeneously expressed among these cells and
      may serve unique roles in different regions of the olfactory bulb.

PMID- 14643768
TI  - Dynorphin A (1-17) induces apoptosis in striatal neurons in vitro through alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor-mediated
      cytochrome c release and caspase-3 activation.
AB  - Dynorphin A (1-17), an endogenous opioid neuropeptide, can have
      pathophysiological consequences at high concentrations through actions involving
      glutamate receptors. Despite evidence of excitotoxicity, the basic mechanisms
      underlying dynorphin-induced cell death have not been explored. To address this
      question, we examined the role of caspase-dependent apoptotic events in mediating
      dynorphin A (1-17) toxicity in embryonic mouse striatal neuron cultures. In
      addition, the role of opioid and/or glutamate receptors were assessed
      pharmacologically using dizocilpine maleate (MK(+)801), a non-equilibrium N
      methyl-D-aspartate (NMDA) antagonist; 6-cyano-7-nitroquinoxaline-2,3-dione, a
      competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate
      antagonist; or (-)-naloxone, a general opioid antagonist. The results show that
      dynorphin A (1-17) (>or=10 nM) caused concentration-dependent increases in
      caspase-3 activity that were accompanied by mitochondrial release of cytochrome c
      and the subsequent death of cultured mouse striatal neurons. Moreover, dynorphin
      A-induced neurotoxicity and caspase-3 activation were significantly attenuated by
      the cell permeable caspase inhibitor, caspase-3 inhibitor-II (z-DEVD-FMK),
      further suggesting an apoptotic cascade involving caspase-3. AMPA/kainate
      receptor blockade significantly attenuated dynorphin A-induced cytochrome c
      release and/or caspase-3 activity, while NMDA or opioid receptor blockade
      typically failed to prevent the apoptotic response. Last, dynorphin-induced
      caspase-3 activation was mimicked by the ampakine CX546 [1-(1,4-benzodioxan-6
      ylcarbonyl)piperidine], which suggests that the activation of AMPA receptor
      subunits may be sufficient to mediate toxicity in striatal neurons. These
      findings provide novel evidence that dynorphin-induced striatal neurotoxicity is
      mediated by a caspase-dependent apoptotic mechanism that largely involves
      AMPA/kainate receptors.

PMID- 14643771
TI  - Molecular and behavioral analysis of the R6/1 Huntington's disease transgenic
      mouse.
AB  - Transgenic mice expressing exon 1 of the human Huntington's disease (HD) gene
      carrying a 115 CAG repeat (line R6/1) are characterized by a neurologic phenotype
      involving molecular, behavioral and motor disturbances. We have characterized the
      R6/1 to establish a set of biomarkers, which could be semi-quantitatively
      compared. We have measured motor fore- and hindlimb coordination, fore- and
      hindpaw footprinting, general activity and anxiety, feetclasping, developmental
      instability. Molecular investigations involved measurements of cannabinoid
      receptor 1 mRNA, met-enkephalin peptide, dopamine and cyclic AMP-regulated
      phosphoroprotein 32 kDa and neuronal inclusions. Molecular and behavioral testing
      was performed on female hemizygotic R6/1 transgenic mice and female wildtype
      littermates between 6 and 36 weeks of age. We show that the cannabinoid receptor
      1 receptor is severely and rapidly downregulated in the R6/1 mouse between the
      8(th) to the 10(th) week of age. At 14 weeks of age the first transgenic mice
      showed a behavioral phenotype measured by feetclasping. However, there was great
      variation between the individual animals. At 11 weeks of age the mice
      demonstrated progressively increasing developmental instability as measured by
      fluctuating asymmetry. Weight differences were evident by 22 weeks of age. Mice
      tested at 23 and 24 weeks of age showed significant impairments in open field and
      plus-maze analysis respectively. We observed no significant abnormalities in
      stride length of the R6/1 mouse model. As the analyzed parameters are easily
      detected and measured, the R6/1 mouse appears to be a good model for evaluating
      new drugs or types of therapy for HD.

PMID- 14643772
TI  - Does the release of acetylcholine in septal slices originate from intrinsic
      cholinergic neurons bearing p75(NTR) receptors? A study using 192 IgG-saporin
      lesions in rats.
AB  - In previous studies electrically-evoked release of acetylcholine in septal slices
      was demonstrated. The present experiment aimed at verifying if this release
      involved intrinsic neurons bearing p75(NTR) receptors. Long-Evans rats sustained
      injections of 192 IgG-saporin into the medial septum/diagonal band of Broca (0.8
      microg). Sham-operated rats served as controls. Two to 3.5 weeks later, the
      electrically-evoked release of acetylcholine ([(3)H]ACh) was measured in slices
      from the lateral septum (LS), medial septum (MS) and diagonal band of Broca
      (DBB). Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity,
      and monoamine concentrations were measured in the septum, cortex and hippocampus.
      The lesion extent was also assessed by ChAT immunostaining in a separate series
      of rats. In the septum, the number of ChAT-positive neurons was depleted
      dramatically (>90% at the level of the injection site). In the hippocampus, the
      lesions reduced ChAT and AChE activity by 91% and 84%, respectively. In the
      cortex, this reduction was weaker (-55% and -47%). In the septal region, the
      reduction was either weak or not significant. The evoked release of acetylcholine
      in septal slices was not reduced, except in the slices from the LS (-64%). The
      effects of physostigmine and atropine confirmed the presence of autoreceptors.
      Our data exclude that a major part of the acetylcholine released by MS and DBB
      slices derived from intrinsic neurons bearing p75(NTR) receptors. In the LS, part
      of the released acetylcholine might be from projections of such neurons located
      in the LS, MS and/or DBB. These data also suggest that the MS and the DBB may be
      the target of extrinsic cholinergic innervation that does not bear p75(NTR)
      receptors.

PMID- 14643773
TI  - The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in
      mice: involvement of proinflammatory factors: nitric oxide and prostaglandins.
AB  - Central nervous system (CNS) inflammation in cases such as head trauma, infection
      and stroke has been associated with the occurrence of epileptic seizures.
      Microglia, the principal immune cells in the brain, readily become activated in
      response to injury, infection or inflammation. The bacterial endotoxin
      lipopolysaccharide (LPS) induces the activation of microglia and the production
      of proinflammatory factors including nitric oxide (NO) and prostaglandins (PGs).
      We examined the effect of LPS on seizure susceptibility of mice, by using the
      sensitive test, threshold of clonic seizures induced by i.v. infusion of
      pentylenetetrazole. LPS decreased the seizure threshold in a dose- and time
      dependent manner. Pretreatment of mice with the NO synthase inhibitor, N(G)-nitro
      L-arginine methyl ester or cyclooxygenase inhibitor, piroxicam or the opioid
      receptor antagonist, (-)-naloxone completely reversed the proconvulsant effect of
      LPS. These results indicate that NO, PGs and endogenous opioid peptides seem to
      be involved in LPS-induced decrease in seizure threshold.

PMID- 14643774
TI  - Exacerbated status epilepticus and acute cell loss, but no changes in
      epileptogenesis, in mice with increased brain-derived neurotrophic factor
      signaling.
AB  - Several studies suggest that brain-derived neurotrophic factor (BDNF) can
      exacerbate seizure development during status epilepticus (S.E.) and subsequent
      epileptogenesis in the adult brain. On the other hand, evidence exists for the
      protective effect of BDNF. To study this controversy, we induced S.E. with
      kainate in transgenic mice with increased BDNF signaling due to trkB
      overexpression. Transgenic mice experienced a more severe S.E. than wild type
      animals did. Furthermore, they had increased acute hippocampal neuronal loss when
      assessed at 48 h after S.E. The effect of trkB overexpression on the development
      of epilepsy, chronic neuronal death, mossy fiber sprouting, and neurogenesis were
      studied at 4.5 months after kainate-induced S.E. No differences were found in the
      rate of epileptogenesis, severity of epilepsy, or cellular markers of network
      reorganization between transgenic and wild type mice. No differences between
      genotypes were observed in TUC-4 staining, indicating no effect of trkB
      overexpression to immature neuron numbers. Instead, in Cresyl Violet-stained
      preparations, the highest density of neurons was found in untreated transgenic
      mice suggesting a favorable effect of trkB overexpression on the survival of
      neurons in the hippocampus. Our data support the role of BDNF and trkB signaling
      in seizure generation and acute cellular damage after S.E. Long-term outcome was
      not, however, exacerbated by trkB overexpression.

PMID- 14643775
TI  - Neurons containing tuberoinfundibular peptide of 39 residues project to limbic,
      endocrine, auditory and spinal areas in rat.
AB  - Accumulating evidence suggests that tuberoinfundibular peptide of 39 residues
      (TIP39) may be the endogenous ligand of the parathyroid hormone 2 receptor. The
      vast majority of TIP39-containing neurons are localized in two regions, the
      subparafascicular area at the thalamic-midbrain junction, and the medial
      paralemniscal nucleus in the rostral pons. In contrast to the restricted
      localization of TIP39-containing cell bodies, TIP39-containing fibers have a
      widespread distribution. TIP39 neurons were lesioned electrolytically to
      determine the origin of TIP39-containing fibers within different parts of the rat
      CNS. Following bilateral lesions of the medial subparafascicular area including
      the subparafascicular nucleus, TIP39-immunoreactive fibers almost completely
      disappeared from forebrain regions including the anterior limbic cortical areas,
      the shell and cone portions of the nucleus accumbens, the lateral septum, the bed
      nucleus of the stria terminalis, the amygdaloid nuclei, the fundus striati, the
      subiculum, the thalamic paraventricular nucleus, and the hypothalamic
      paraventricular, dorsomedial and arcuate nuclei. Unilateral lesions of the medial
      and the lateral subparafascicular area demonstrated that the projections are
      ipsilateral and that medial lesions produce higher reductions in the density of
      TIP39 fibers except in the amygdala and the hypothalamus. Following lesions of
      the medial paralemniscal nucleus, TIP39-immunoreactive fibers disappeared from
      the medial geniculate body, the periaqueductal gray, the deep layers of the
      superior colliculus, the external cortex of the inferior colliculus, the
      cuneiform nucleus, the nuclei of the lateral lemniscus, the lateral parabrachial
      nucleus, the locus coeruleus, the subcoeruleus area, the medial nucleus of the
      trapezoid body, the periolivary nuclei, and the spinal cord, suggesting that
      these regions receive TIP39-containing fibers from the medial paralemniscal
      nucleus, and unilateral lesions demonstrated that the projections are
      ipsilateral. The projections of the TIP39-containing cells in the
      subparafascicular area suggest their involvement in limbic and endocrine
      functions, while the projections of the TIP39-containing cells in the medial
      paralemniscal nucleus suggest their involvement in auditory and nociceptive
      functions.

PMID- 14643776
TI  - Adenosinergic inhibition of basal forebrain wakefulness-active neurons: a
      simultaneous unit recording and microdialysis study in freely behaving cats.
AB  - The majority of neurons in the magnocellular basal forebrain are wakefulness
      active with highest discharge activity during wakefulness and a marked reduction
      in activity just before and during the entry to non-rapid eye movement (REM)
      sleep. We have hypothesized that the reduction of discharge activity of
      wakefulness-active neurons and a consequent facilitation of the transition from
      wakefulness to sleep is due to an increase in the extracellular concentration of
      adenosine during wakefulness. To test the hypothesis, the present study employed
      microdialysis perfusion of adenosinergic pharmacological agents combined with
      single unit recording in freely moving cats, so as to determine: 1). if there
      were dose-dependent effects on behaviorally identified wakefulness-active
      neurons; 2). whether effects were mediated by the A1 receptor, as contrasted to
      the A2a receptor; and 3). if effects were specific to wakefulness-active neurons,
      and not present in sleep-active neurons, those preferentially discharging in
      nonREM sleep. Both adenosine and the A1 receptor-specific agonist N6-cyclo-hexyl
      adenosine reduced the discharge activity of wakefulness-active neurons (n=16) in
      a dose-dependent manner but had no effect on sleep-active neurons (n=4). The A1
      receptor antagonist 8-cyclopentyl-1-3-dimethylxanthine increased the discharge of
      wakefulness-active neurons (n=5), but the A2a receptor agonist, CGS-16284, had no
      effect (n=3). Recording sites were histologically localized to the cholinergic
      basal forebrain. These data support our hypothesis that adenosine acts via the A1
      receptor to reduce the activity of wakefulness-promoting neurons, thus providing
      a cellular mechanism explaining why the increased adenosine concentrations
      observed in the basal forebrain following prolonged wakefulness act to induce
      sleep.

PMID- 14643777
TI  - Rates and totals: population pressures on habitat.

PMID- 14643778
TI  - Effects of disturbances caused by coastal constructions on spatial structure,
      growth dynamics and photosynthesis of the seagrass Posidonia oceanica.
AB  - The light-limitation hypothesis was tested to assess whether water turbidity had
      caused the decline of a Mediterranean Posidonia oceanica (L.) Delile meadow in an
      area affected by a harbor. The annual growth, photosynthesis and rhizome starch
      concentrations of seagrass were measured and related to changes in light
      availability and dissolved nutrient concentration along a gradient of meadow
      degradation from areas close to the harbor outwards. Environmental and plant
      variables were measured in three stations placed along this gradient and compared
      with a reference station at an undisturbed meadow. The light attenuation
      coefficient (k) increased toward the inner harbor area, mainly due to sediment
      resuspension. The shoot density and leaf productivity of P. oceanica shoots were
      much lower in disturbed stations of the inner harbor area than in the outer, less
      disturbed station and the reference meadow. However, daily leaf carbon gains,
      calculated from the photosynthetic rates at saturating irradiance (P(max)) and
      the daily period in which seagrass receives light higher than its saturating
      irradiance (H(sat)), suggested positive C-balance in all stations. This was
      partly explained by photo-acclimatization of seagrass to the reduced light
      availability at the disturbed harbor stations (inner and intermediate), as
      indicated by the lengthening of H(sat) and the decrease in saturating irradiance
      (I(sat)) and respiratory demands. Despite photo-acclimatization, disturbed harbor
      stations showed less positive C-balance, seen not only in their lower leaf growth
      and biomass but also in a decrease in rhizome carbohydrate reserves (starch). Our
      results suggest that light reduction account for the reduced seagrass
      productivity and abundance. However, meadow decline (in terms of shoot mortality)
      in the harbor area is well above that predicted from similar light environments
      of nearby meadows or simulated in shading experiments. Thus, there are other
      factors than light limitation involved in seagrass mortality, most probably
      through more complex interactions (e.g. nutrient-epiphytes-grazers, water quality
      -siltation).

PMID- 14643779
TI  - Marine debris surveys at Volunteer Beach, Falkland Islands, during the summer of
      2001/02.
AB  - This survey evaluated the monthly accumulation rate of marine debris and the
      types of objects washed ashore at Volunteer Beach on East Falkland between
      October 2001 and March 2002. The mean (+/-SD) accumulation rate of marine debris
      was 77+/-25 items/km/month, of a mean weight of 17.3+/-12 kg. Forty different
      objects were collected and the five most frequent items were cotton fabric,
      string, polystyrene packing sheet, plastic packing tape and broken plastic
      pieces. The debris on Volunteer Beach was dominated by fishing debris; 42% of the
      items were discarded fishing equipment, while 39% of the items were of a
      packaging or associated nature. The mostly likely source of this household waste
      was fishing vessels, with Falkland Islands Government (FIG) fisheries observers
      seeing 27 of the 40 items of debris collected from Volunteer Beach being
      discarded from fishing vessels. It is suggested that, although further marine
      debris research is warranted, more effective at-sea ship waste disposal
      regulations are required in Falkland waters to reduce environmental and economic
      threats both at the local and international level.

PMID- 14643780
TI  - Restoration of the eutrophic Orbetello lagoon (Tyrrhenian Sea, Italy): water
      quality management.
AB  - The Orbetello lagoon (Tyrrhenian coast, Italy) receives treated urban and land
      based fishfarms wastewater. The development of severe eutrophication imposed the
      three main activity adoption focuses on (1) macroalgae harvesting; (2) pumping of
      water from the sea; (3) confining wastewater to phytotreatment ponds. The
      responses to these interventions were rapid and macroalgal reduction growth and
      seagrass return were recorded. Since 1999, a new macroalgal development was
      recorded. The aim of this research was to discover whether the recent macroalgal
      growth can be attributed to the continuing wastewater influx from the remaining
      persistent anthropic sources (PAS) or from the sediment nutrient release. A
      monitoring programme was carried out between August 1999 and July 2000 in order
      to measure dissolved inorganic nitrogen and phosphorus in the wastewaters
      entering into the lagoon and in central lagoon areas, seaweed and seagrass
      distribution and lagoon N, P annual budgets. The results showed higher N and P
      values close to PAS. The distribution of the macroalgal species confirms that the
      available P comes almost entirely from these remaining PAS. In conclusion, the
      environmental measures adopted produced a significant reduction in algal biomass
      development in the lagoon; the macroalgal harvesting activities produced a
      sediment disturbance with following oxidize conditions, which make P unavailable
      in the lagoon water, excepting close the PAS.

PMID- 14643781
TI  - Relative importance of dissolved and food pathways for lead contamination in
      shrimp.
AB  - The relative importance of dissolved and food pathways and the influence of food
      type in the bioaccumulation and retention of lead in the shrimp Palaemonetes
      varians were examined using a radiotracer method. Shrimp were exposed to 210Pb
      labelled seawater or fed two types of 210Pb-labelled food, viz. mussels or worms.
      The amount of radiotracer accumulated by shrimp was examined over a 7-day period,
      followed by a 1-month and a 7-day depuration period for the dissolved and food
      source, respectively. Steady state in the uptake was reached after 2 days
      exposure to dissolved lead, with a resultant estimated concentration factor of
      98+/-3. Transfer factors following ingestion of contaminated mussels and worms
      were lower than unity for both food types, with lead transfer from worms being
      significantly higher than that from mussels. Accumulation of dissolved Pb by
      shrimp was found to occur mainly through adsorption on the exoskeleton with a
      minor accumulation in the internal tissues probably resulting from the intake of
      seawater for osmoregulation. In contrast, lead taken up from contaminated food
      was readily absorbed and bound in the internal tissues of P. varians. Although
      the transfer of lead to P. varians through the ingestion of contaminated food was
      low (TF<1%), it still represented 4 to 8% of the lead content in the prey which
      is a significant additional contribution of lead to the shrimp body burden.
      Independent of food type, following ingestion of contaminated food, approximately
      23-27% of total lead accumulated in shrimp was located in the edible parts (e.g.
      muscle). Therefore, the food pathway is suggested to be a significant contributor
      to the lead transfer to humans through ingestion of contaminated shrimp. After
      exposure to contaminated food, lead loss kinetics were described by a two
      component model, whereas Pb loss following direct uptake from seawater was best
      described by a three-component model. The additional compartment representing 64%
      of total Pb retained and characterized by a turnover<10 min, corresponded to lead
      weakly adsorbed on the exoskeleton and incorporated in the hepatopancreas.
      Nevertheless, a significant fraction of lead accumulated from the dissolved (2%)
      and food (52-57%) pathways remained irreversibly retained in the tissues,
      suggesting that this organism could also serve as an effective long-term
      bioindicator of lead contamination in marine waters.

PMID- 14643782
TI  - Activity concentration of caesium-137 in seawater and plankton of the Pomeranian
      Bay (the Southern Baltic Sea) before and after flood in 1997.
AB  - Activity coefficients of 137Cs determined during culminating flood waters in
      August 1997 in the estuary of the Oder River, discharging to the Pomeranian Bay
      as well as in the coastal and open-seawaters of the Bay, did not show enhanced
      levels of the nuclide as compared to those measured before the flood. It is thus
      concluded that the flood did not contribute to releasing the nuclide from eroded
      soil particles. The bioconcentration factors of 137Cs in the riverine plankton
      has been found to be one to two orders of magnitude higher than those determined
      in the Pomeranian Bay plankton.

PMID- 14643783
TI  - Effect of size, tissue parts and location on six biochemical markers in the green
      lipped mussel, Perna viridis.
AB  - The effect of size and tissue parts as well as site locations on a suite of six
      anti-oxidative biochemical markers, viz. the enzyme degrading neural transmitters
      acetylcholinesterase (AChE), the Phase II transforming enzyme glutathione-S
      transferase (GST), the anti-oxidative enzymes superoxide dismutase (SOD) and
      catalase (CAT), the lipid metabolite malondialdehyde (MDA) and the ratio of
      CAT/MDA, in the bivalve mollusc, Perna viridis, was studied. Field mussels were
      collected from the piers of University of Science and Technology (UST), Pak Sha
      Wan or Hebe Haven (PS) and Sai Kung (SK) in Port Shelter, Hong Kong.
      Statistically, ANOVA showed that the activity of all six biochemical markers were
      generally tissue dependent, size independent and location dependent. Tukey multi
      comparison test indicated that the biochemical activities fell into two groups,
      with SK the highest activity group in most cases. The significance of these
      findings in relation to long-term coastal water biomonitoring is discussed.

PMID- 14643784
TI  - Trace metals in the living and nonliving components of scleractinian corals.
AB  - Trace metals in coral tissue and skeleton have been investigated in various ways
      since the early seventies. More recently it has been suggested that the symbiotic
      zooxanthellae may play an important role in the accumulation and regulation of
      trace metals. Furthermore gamete development and mucus production may influence
      the metal accumulation and loss in corals. Many studies have attempted to use the
      annual growth bands in coral skeletons to investigate historical pollution
      events. However the relationship between the metal concentrations in the
      surrounding environment and the incorporation of this into coral skeleton is not
      well understood. This paper explains a method for investigating metal loads in
      coral tissue, zooxanthellae and skeleton. Furthermore, it presents new
      information suggesting that zooxanthellae accumulate most metals (Al, Fe, As, Mn,
      Ni, Cu, Zn, Cd, Pb) in greater concentrations than the coral tissue. Coral
      skeletons had consistently lower metal concentration than the zooxanthellae,
      tissue and gametes. The loss of zooxanthellae during stress events may have a
      significant contribution to the total metal loads in corals. The use of corals as
      biomonitors should carefully factor in zooxanthellae densities and gamete
      development before conclusions are drawn.

PMID- 14643785
TI  - Variations in benthic fauna underneath an effluent mixing zone at a marine oil
      terminal in Port Valdez, Alaska.
AB  - The distributions of hydrocarbons and infauna in sediments below a permitted
      mixing zone for the disposal of treated ballast waters in Port Valdez, Alaska
      were examined annually, 1999-2001. The associations of biological measures and
      the abundance of selected benthic organisms to total aromatic hydrocarbons (TARO)
      ranged up to large-sized effects, as compared against minimum-effect criteria
      (/r/> or =0.63). The apparent sensitivity of three polychaete worms to low levels
      of hydrocarbons makes them particularly useful as indicators of future changes in
      spatial distributions of hydrocarbons associated with discharged effluent. In
      2001, sediment TARO concentrations decreased and the correlation values of TARO
      to biotic variables were generally less than in 1999 and 2000. Evidence supports
      a conclusion of a strong but spatially limited association of some fauna with
      accumulations of petroleum hydrocarbons in these sediments.

PMID- 14643786
TI  - Adjustment of benthic fauna following sediment disposal at a site with multiple
      stressors in Port Valdez, Alaska.
AB  - The shallow subtidal macrobenthos at Port Valdez, Alaska, was examined to assess
      faunal adjustment following disposal of dredged sediments over a three-year
      period. Prior to sediment disposal, the infauna consisted of a relatively species
      rich assemblage dominated by sessile polychaetes and bivalves. Six months after
      disposal, virtually all taxa present prior to dredging and disposal were rare or
      absent with opportunistic taxa dominant. Surveys performed 1.5 years after
      sediment disposal indicated faunal adjustment was in progress; large, sessile
      polychaetes and bivalves were still present in low numbers after 2.5 years. At
      one station, increasing organic enrichment by fish-wastes from adjacent
      processing plants resulted in a shift to a highly disturbed benthic assemblage.
      The trends in the faunal assemblage suggest that environmental conditions were
      still in a state of flux 2.5 years after the dredging event.

PMID- 14643787
TI  - Investigations into the bioavailability and bioaccumulation of mercury and other
      trace metals to the sea cucumber, Sclerodactyla briareus, using in vitro
      solubilization.
AB  - The in vitro solubilization and bioaccumulation of mercury and other trace metals
      by the intestinal fluid of the sea cucumber, Sclerodactyla briareus, was
      investigated. Sediments were incubated with intestinal fluid and the intestinal
      fluid was analyzed for the in vitro experiments. Experiments examined both
      procedural effects of in vitro solubilization and bioaccumulation of trace metals
      by the sea cucumber. Both solubilization and bioaccumulation were compared among
      the different metals. This comparison revealed that monomethylmercury (MMHg)
      solubilization and bioaccumulation is greater than Hg(I); Cd solubilization is
      higher than MMHg and Hg(I); and Cu and Pb solubilization is similar to MMHg and
      slightly higher than Hg(I). Solubilization and bioaccumulation was found to be
      very low, except for Cd, which had high relative solubilization but low
      bioaccumulation. It was concluded that while solubilization could be the rate
      limiting step for certain metals, other factors, such as depuration and membrane
      transport, may influence overall bioaccumulation of the other metals.

PMID- 14643788
TI  - Quantification and classification of ship scraping waste at Alang-Sosiya, India.
AB  - Alang-Sosiya located on the Western Coast of Gulf of Cambay, is the largest ship
      recycling yard in the world. Every year on average 365 ships having a mean weight
      (2.10x10(6)+/-7.82x10(5) LDT) are scrapped. This industry generates a huge
      quantity of solid waste in the form of broken wood, rubber, insulation materials,
      paper, metals, glass and ceramics, plastics, leather, textiles, food waste,
      chemicals, paints, thermocol, sponge, ash, oil mixed sponges, miscellaneous
      combustible and non-combustible. The quantity and composition of solid waste was
      collected for a period of three months and the average values are presented in
      this work. Sosiya had the most waste 15.63 kg/m(2) compared to Alang 10.19
      kg/m(2). The combustible solid waste quantity was around 83.0% of the total solid
      waste available at the yard, which represents an average weight of 9.807 kg/m(2);
      whereas, non-combustible waste is 1.933 kg/m(2). There is not much difference
      between the average of total solid waste calculated from the sampling data (96.71
      MT/day) and the data provided by the port authorities (96.8 MT/day).

PMID- 14643789
TI  - A 150-year reconstruction of the history of coastal eutrophication in Roskilde
      Fjord, Denmark.

PMID- 14643790
TI  - Evidence of oil leakage from the Bahia Paraiso wreck in Arthur Harbour,
      Antarctica.

PMID- 14643791
TI  - Trace metal distribution and relation to marine sediment mineralogy, Gulf of
      Carpentaria, Northern Australia.

PMID- 14643793
TI  - Lipidomics is emerging.

PMID- 14643794
TI  - Regulation of myocardial triacylglycerol synthesis and metabolism.
AB  - Studies showing a correlation of excess myocardial triacylglycerol stores with
      apoptosis, fibrosis, and contractile dysfunction indicate that dysregulation of
      triacylglycerol metabolism may contribute to cardiac disease. This review covers
      the regulation of heart triacylglycerol accumulation at the critical control
      points of fatty acid uptake, enzymes of triacylglycerol synthesis, lipolysis, and
      lipoprotein secretion. These pathways are discussed in the context of the central
      role myocardial triacylglycerol plays in cardiac energy metabolism and heart
      disease.

PMID- 14643795
TI  - Reduced atherosclerosis in hormone-sensitive lipase transgenic mice
      overexpressing cholesterol acceptors.
AB  - Macrophage-specific overexpression of cholesteryl ester hydrolysis in hormone
      sensitive lipase transgenic (HSL Tg) female mice paradoxically increases
      cholesterol esterification and cholesteryl ester accumulation in macrophages, and
      thus susceptibility to diet-induced atherosclerosis compared to nontransgenic
      C57BL/6 mice. The current studies suggest that whereas increased cholesterol
      uptake could contribute to transgenic foam cell formation, there are no
      differences in cholesterol synthesis and the expression of cholesterol efflux
      mediators (ABCA1, ABCG1, apoE, PPARgamma, and LXRalpha) compared to wild-type
      macrophages. HSL Tg macrophages exhibit twofold greater efflux of cholesterol to
      apoA-I in vitro, suggesting the potential rate-limiting role of cholesteryl ester
      hydrolysis in efflux. However, macrophage cholesteryl ester levels appear to
      depend on the relative efficacy of alternate pathways for free cholesterol in
      either efflux or re-esterification. Thus, increased atherosclerosis in HSL Tg
      mice appears to be due to the coupling of the efficient re-esterification of
      excess free cholesterol to its limited removal mediated by the cholesterol
      acceptors in these mice. The overexpression of cholesterol acceptors in HSL-apoA
      IV double-transgenic mice increases plasma HDL levels and decreases diet-induced
      atherosclerosis compared to HSL Tg mice, with aortic lesions reduced to sizes in
      nontransgenic littermates. The results in vivo are consistent with the effective
      efflux from HSL Tg macrophages supplemented with HDL and apoA-I in vitro, and
      highlight the importance of cholesterol acceptors in inhibiting atherosclerosis
      caused by imbalances in the cholesteryl ester cycle.

PMID- 14643796
TI  - Gene structure of pig sterol 12alpha-hydroxylase (CYP8B1) and expression in fetal
      liver: comparison with expression of taurochenodeoxycholic acid 6alpha
      hydroxylase (CYP4A21).
AB  - Cholic acid is the major trihydroxy bile acid formed in most mammals. The
      domestic pig (Sus scrofa) is an exception. The bile of adult pig is devoid of
      cholic acid whereas hyocholic acid is found in amounts equal to that of cholic
      acid in humans. The pathway leading to formation of hyocholic acid is believed to
      be species-specific and to have evolved in the pig to compensate for a
      nonexistent or deficient cholic acid biosynthesis. However, a high level of
      cholic acid has recently been found in the bile of fetal pig. Here we describe
      that a gene encoding the key enzyme in cholic acid biosynthesis, the sterol
      12alpha-hydroxylase (CYP8B1), is in fact present in the pig genome. The deduced
      amino acid sequence shows 81% identity to the human and rabbit orthologues.
      CYP8B1 mRNA is expressed at significant levels in fetal pig liver. Both CYP8B1
      and the key enzyme in hyocholic acid formation, taurochenodeoxycholic acid 6alpha
      hydroxylase (CYP4A21), were found to be expressed in pig liver in a developmental
      dependent but opposite fashion.

PMID- 14643797
TI  - Characterisation of an N-terminal variant of acetyl-CoA carboxylase-alpha:
      expression in human tissues and evolutionary aspects.
AB  - mRNA encoding a variant acetyl-CoA carboxylase (ACC)-alpha isozyme, transcribed
      from a downstream promoter, PIII, was detected in human tissues. Such exon 5A
      containing transcripts (E5A-mRNA) encode ACC-alpha with a distinct N-terminus,
      with 15/17 residues identical to those encoded by the ovine mRNA. In the current
      study we used antisera directed against the E5A N-terminus to verify that ovine
      E5A translates are present in tissues consistent with the distribution of E5A
      mRNA. The presence of E5A alters the context of adjacent regulatory
      phosphorylation sites in E6, which may indicate altered regulation of activity
      for this isozyme. Sequences with high identity to the proximal promoter of PIII
      and E5A are present in the mouse and rat ACC-alpha genes, however, the coding
      region of E5A is not conserved, and E5A transcripts are not detected in tissues.
      Thus E5A must have been present in a common ancestor of rodents, primates, and
      ruminants, and has become nonfunctional in the former. A minor human PIII-derived
      mRNA containing an additional 111-bp sequence encoded by a downstream exon, E5B,
      was also detected. E5B encodes an in-frame stop-codon such that the E5A open
      reading frame is terminated, however, ACC-alpha translation may be re-initiated
      from a downstream AUG in E6, potentially generating an isozyme lacking the N
      terminal phosphorylation sites. Transcription of human ACC-alpha from at least
      three promoters and the potential to generate ACC-alpha isozymes with
      differential susceptibilities to phosphorylation indicate that the regulation of
      fatty acid synthesis in human tissues is likely to be complex.

PMID- 14643798
TI  - A novel lipopeptide, an inhibitor of bacterial adhesion, from the thermophilic
      and halotolerant subsurface Bacillus licheniformis strain 603.
AB  - A new Bacillus licheniformis strain, 603, isolated from a mixture of drilling
      fluid and subsurface thermal water, has been found to produce a cyclic
      lipopeptide which is released into cultural medium as well as present in cells as
      the major lipid constituent (57% of the total cell lipids extractable with 2:1
      chloroform-methanol). The quantitative ratio of the extracellular and
      intracellular lipopeptide has been estimated as 23:10. The metabolite represents
      a heptapeptide, L-Asp-->L-Leu-->L-Leu-->L-Val-->L-Val-->L-Glu-->L-Leu, N-acylated
      to the N-terminal amino acid, L-Asp, by a 3-hydroxy fatty acid (from 13:0 to 17:0
      with n-, iso-, and anteiso-chains), the 3-OH group of which is esterified by the
      C-terminal amino acid, L-Leu. The chemical structure of the lipopeptide has been
      established by means of infrared (IR), 1H- and 13C-nuclear magnetic resonance
      (NMR) spectroscopy, electrospray ionisation (ESI) mass spectrometry (MS),
      including secondary ion mass spectrometry, along with chemical and enzymatic
      degradation. Although a diversity of similar metabolites synthesised by various
      B. licheniformis strains are presently known, such a structure has not been
      reported thus far. Added to the growth medium of strain 603 at the concentration
      of 1.6 microg/ml, the lipopeptide prevents adhesion of cells to a glass surface.
      Also, it exhibits a considerable growth-inhibiting activity against
      Corynebacterium variabilis and a much lower activity against Acinetobacter sp.

PMID- 14643799
TI  - Micelle formation of sodium chenodeoxycholate and solubilization into the
      micelles: comparison with other unconjugated bile salts.
AB  - Micellization of sodium chenodeoxycholate (NaCDC) was studied for the critical
      micelle concentration (CMC), the micelle aggregation number, and the degree of
      counterion binding to micelle at 288.2, 298.2, 308.2, and 318.2 K. They were
      compared with those of three other unconjugated bile salts; sodium cholate (NaC),
      sodium deoxycholate (NaDC), and sodium ursodeoxycholate (NaUDC). The I(1)/I(3)
      ratio of pyrene fluorescence and the solubility dependence of solution pH were
      employed to determine the CMC values. As the results, a certain concentration
      range for the CMC and a stepwise molecular aggregation for micellization were
      found reasonable. Using a stepwise association model of the bile salt anions, the
      mean aggregation number (n) of NaCDC micelles was found to increase with the
      total anion concentration, while the n values decreased with increasing
      temperature; 9.1, 8.1, 7.4, and 6.3 at 288.2, 298.2, 308.2, and 318.2 K,
      respectively, at 50 mmol dm(-3). The results from four unconjugated bile salts
      indicate that the number, location, and orientation of hydroxyl groups in the
      steroid nucleus are quite important for growth of the micelles. Activity of the
      counterion (Na(+)) was determined by a sodium ion selective electrode in order to
      confirm the low counterion binding to micelles. The solubilized amount of
      cholesterol into the aqueous bile salt solutions increased in the order of
      NaUDC<NaC<NaCDC<NaDC. The first stepwise association or solubilization constants
      (K(1)) between a cholesterol monomer and a vacant micelle were evaluated at
      different bile salt concentrations. The constants were also determined for
      polycyclic aromatic compounds (benzene, naphthalene, anthracene, and pyrene). The
      corresponding DeltaG(0) value was most negative for cholesterol among the
      solubilizates studied, which indicated that cholesterol was thermodynamically
      stabilized most by solubilization into the bile salt micelles.

PMID- 14643800
TI  - Post-mitral valve repair systolic anterior motion produced by non-obstructive
      septal bulge.
AB  - OBJECTIVE: Systolic anterior motion (SAM) may rarely occur after mitral valve
      reconstruction due to different anatomic factors. Several techniques have been
      described to reduce the incidence of post-repair SAM, e.g. leaflet sliding
      plasty. However, SAM can still occur after these special procedures. We reviewed
      data of patients developing SAM with significant mitral regurgitation due to non
      obstructive septal bulge. METHODS: During a 2-year period mitral valve repair was
      performed in 358 patients. Five of 358 (1.4%) patients with a mean age of 52+/
      10.5 years developed post-repair SAM with severe mitral insufficiency due to non
      obstructive septal bulge. Data of these patients were analyzed retrospectively
      and controlled after a mean follow-up of 18+/-2.7 months. RESULTS: Preoperative
      echocardiography showed end-diastolic septum diameter of 7, 10, 10, 11 and 15 mm.
      The ratio between end-diastolic septum diameter and free wall diameter was 1 in
      four patients and 1.25 in one patient. There was no left ventricular outflow
      tract obstruction (LVOT). Intraoperative data revealed large myxomatous anterior
      (four patients) and posterior (three patients) leaflets. Quadrangular resection
      of posterior leaflet was carried out in four patients and sliding plasty in one
      patient. Cause for post-repair mitral regurgitation was a non-obstructive septal
      bulge. During a second pump run septal bulge was resected. Mean aortic cross
      clamp time and cardiopulmonary bypass time for this procedure was 15+/-1.4 and
      28+/-3.1 min, respectively. Mitral regurgitation disappeared in all patients
      immediately after this procedure. The grade of mitral regurgitation at follow-up
      was 0-1 in all patients. One patient had subaortic gradient of 36 mmHg.
      CONCLUSIONS: If mitral regurgitation occurs after primary successful mitral
      repair, septum bulge should always be considered as the primary cause for SAM
      even there is no preoperative gradient in LVOT. Before performing time-consuming
      corrective operations to relieve SAM, a septum resection should be carried out
      during a short second pump run.

PMID- 14643801
TI  - Superior septal approach for mitral valve surgery: a word of caution.
AB  - OBJECTIVE: Superior septal approach provides excellent exposure of the mitral
      valve and the subvalvular structures. The unavoidable section of the sinus node
      artery is in relationship with this technique. We have studied the electrical
      changes associated after using this approach. MATERIAL AND METHODS: We studied
      247 cases of mitral valve surgery from 1996 to 2003. The patient population was
      divided into two comparative groups: group I (128 cases) was represented by the
      superior septal approach and group II (119 cases) composed the conventional right
      lateral approach through the left atrium. Preoperatively, 48 patients (37.5%) in
      group I and 46 (38.6%) in group II were in a normal sinus rhythm. Mean follow-up
      was 30.7 months in group I and 33.5 months in group II. RESULTS: There was no
      mortality in group I and eight cases (6.7%) in group II. A high incidence of
      changes as junctional rhythm was observed in group I, especially after weaning of
      cardiopulmonary bypass and on the first day after surgery (P>0.001).
      Postoperative P-R interval of the patients in sinus rhythm was 100+/-30 ms in
      group I and 148+/-24 ms in group II (P>0.05). P-R interval in group I was shorter
      than normal. P-wave morphology changed becoming inverted in leads II, III and aVF
      after surgery in these cases in group I. A full recuperation in P-R interval and
      the P-wave axis was seen in 52 cases (87.5%) in patients in group I after the
      third postoperative month. A definitive pacemaker implantation was need in two
      cases (1.5%) in group I and in six (5%) in group II (P>0.05). CONCLUSIONS: A
      superior septal approach is directly related with the loss of normal sinus rhythm
      because of the section of the sinus node artery. After a brief period of
      transient electrical changes, a new low atrial or coronary sinus rhythm slower
      than normal sinus rhythm appears. In consequence, a word of caution must be
      strongly considered in patients critically dependent on normal sinus rhythm,
      despite the low incidence of definitive electrical changes. Normal sinus rhythm
      appears again after the third postoperative month.

PMID- 14643802
TI  - Surgery for prosthetic valve obstruction. A single center study of 136 patients.
AB  - OBJECTIVES: Prosthetic heart valve obstruction (PHVO) is a potentially fatal
      complication of heart valve replacement with mechanical substitute mainly due to
      thrombosis. The purpose of this report is to present a single-center experience
      of 136 consecutive patients operated on between 1978 and 2001. METHODS: The
      diagnosis of PHVO was mainly assessed by fluoroscopy and/or echocardiography.
      Thrombosed valves were bileaflet (82), tilting disc (47) and ball cage (7)
      valves; of these, 90 were in mitral, 38 in aortic, six in aortic and mitral
      position, and two in tricuspid position. The mean interval between the first
      implantation and valve thrombosis was 7.4+/-6.6 years (range 1 day to 28 years);
      in 37 patients preoperative medical therapy (fibrinolysis in 21, and heparin
      alone in 16) was unsuccessful. RESULTS: Operative procedures included valve re
      replacement in 104 cases and declotting-pannus excision in 32 cases. Early
      hospital mortality was 10.3% (14 patients), all in NYHA class III or IV, and one
      patient suffered a perioperative cerebral embolic event. Surgery was then
      successful in 121 of 136 patients (89%), but during a 3.15-year follow-up,
      prosthetic heart valve thrombosis recurred in ten out of 122 survivors (8.1%).
      CONCLUSION: From this experience, it can be concluded that for most PHVO, early
      operation is currently effective and safe, especially in patients in stable
      hemodynamic condition preoperatively.

PMID- 14643803
TI  - Re-operation for bioprosthetic aortic structural failure - risk assessment.
AB  - OBJECTIVE: The predominant complication of bioprostheses is structural valve
      deterioration and the consequences of re-operation. Prosthesis choice for aortic
      valve replacement surgery (bioprostheses and mechanical prostheses), is
      influenced by valve-related complications (mortality and morbidity) of the
      prosthesis type chosen. The purpose of the study is to determine the mortality
      and risk assessment of that mortality for aortic bioprosthetic failure. METHODS:
      From 1975 to 1999, 3356 patients received a heterograft bioprosthesis in 3530
      operations. The procedures were performed with concomitant coronary artery bypass
      (CAB) in 1388 procedures and without in 2142 procedures. Three hundred twenty-two
      re-operations for structural valve deterioration were performed in 312 patients
      with 22 fatalities (6.8%). Of the 322 re-replacements, 36 had CAB and 286 had
      isolated replacement; the mortality was 8.3% (3) and 6.6% (19), respectively.
      Eleven predictive factors inclusive of age, concomitant CAB, urgency status, New
      York Heart Association (NYHA) at Re-op and year of Re-op (year periods) were
      considered. RESULTS: The mortality for 1979-1986 was 6.1% (2/33); 1987-1992, 7.7%
      (8/104); and 1993-2000, 6.5% (12/185) (pNS). The mortality by urgency status for
      elective/urgent was 6.4% (19/299); and emergent, 13.0% (3/23) (pNS). The
      mortality for NYHA I/II was 2.0% (1/50), III 4.2% (8/191) and IV 16.0% (13/81)
      (P=0.00063), for gender was male 4.6% and female 13.3% (P=0.011), for age at
      implant 'No' (no re-operation) 51.6+/-12.2 years and 'Yes' (yes re-operation)
      59.9+/-7.3 years (P=0.00004), for age at explant 'No' 62.6+/-12.7 years and 'Yes'
      70.6+/-6.5 years (P=0.00001), and for age at explant <60 years 0.0% (0/110), 60
      70 years 8.5% (10/117) and >70 years 12.6% (12/95) (P=0.0011). The predictive
      risk factor assessment by multivariate regression analysis revealed only NYHA III
      Odds Ratio 1.7 and IV 7.8 P=0.0082. For the period 1993-2000 of re-operations
      only gender was significant; age at implant, age at explant, CAB pre-Re-op, CAB
      concomitant with Re-op, urgency at Re-op, ejection fraction, valve lesion and
      NYHA at Re-op were not significant. CONCLUSIONS: Bioprosthetic aortic re
      operative mortality can be lowered by re-operation in low rather than medium to
      severe NYHA functional class. The routine evaluation of patients can achieve
      earlier low risk re-operative surgery.

PMID- 14643804
TI  - Aortic valve replacement in severe aortic stenosis with left ventricular
      dysfunction: determinants of cardiac mortality and ventricular function recovery.
AB  - OBJECTIVE: The influence of left ventricular (LV) dysfunction on survival of
      patients with severe aortic stenosis is poorly characterized. Few data are
      available about preoperative predictors of cardiac mortality and LV function
      recovery after aortic valve replacement of such patients. The aim of our study
      was to examine the outcome and the preoperative predictors of postoperative
      cardiac death and of LV function recovery in these patients. METHODS: We
      evaluated 85 consecutive patients with severe aortic stenosis (aortic valve area
      <1 cm(2)) and severe depression of LV ejection fraction (EF) <35% at cardiac
      catheterization. Among them, 52 underwent aortic valve replacement and they were
      compared to patients who were not operated on. All patients had a mean clinical
      follow-up of 53 months and 94% of them had a mean echocardiographic follow-up of
      14 months after aortic valve replacement. RESULTS: The mean baseline
      characteristics included: LVEF 28+/-6%, peak-to-peak transvalvular gradient 51+/
      29 mmHg, aortic valve area 0.63+/-0.25 cm(2). Thirty-three patients did not
      undergo aortic valve replacement: 32 of them died within 3 years. Fifty-two
      patients underwent aortic valve replacement and 16 had a concomitant coronary
      bypass surgery. In-hospital mortality was 8%. Postoperative NYHA functional class
      changed from 2.84+/-0.67 to 1.43+/-0.44 (P<0.001) and LVEF from 29+/-6% to 43+/
      10% (P<0.001). At follow-up 10 patients died of heart disease. By multivariate
      analysis, preoperative LV end-systolic volume index (ESVI) was the only covariate
      of cardiac death (LVESVI/10 ml/m(2), OR 1.3, CI 1.1-1.8, P<0.028). By using a
      receiver operating characteristic curve, LVESVI< or =90 ml/m(2) was the best cut
      off value (sensitivity and specificity 78%) to fit with a better survival (93%
      vs. 63%, P<0.01) and with LVEF recovery after aortic valve replacement (EF
      improved by 15+/-10% vs. 8+/-5%, P<0.001). CONCLUSIONS: Despite LV dysfunction,
      aortic valve replacement appears to change drastically the natural history of
      severe aortic stenosis. Preoperative LV levels predict different postoperative
      survival rate and LVEF recovery.

PMID- 14643805
TI  - Aortic valve leaflet sparing and salvage surgery: evolution of techniques for
      aortic root reconstruction.
AB  - Over the past 20 years, a series of procedures have been designed to reconstruct
      the aortic root of patients with aortic insufficiency, in whom the pathology and
      hence the surgery spares the valve leaflets. Such techniques have various names.
      Usually 'valve sparing' is used in context with chronic aortic dissection or
      aortic root aneurysm as in patients with Marfan's syndrome. 'Aortic valve
      salvage' tends to be the term of choice for similar surgical reconstruction in
      the setting of aortic dissection. 'Aortic valve repair' is often chosen when
      direct surgical procedures are performed on the leaflets themselves. All of the
      techniques have evolved based upon an increased understanding of the functional
      anatomy of the aortic root complex. The different technical approaches, their
      applications and results need to be understood by the cardiology community. The
      failure modes for such techniques are specific and different from prosthetic
      valve failure modes, but are adequately followed with echocardiography. Over two
      thirds of patients remain free of re-development of significant aortic
      insufficiency at 8-10 years following surgery. The overall patient survival is
      more dependent upon the underlying cardiovascular status of the patient than the
      surgical technique itself. Perioperative mortalities vary between 0 and 6% and
      are comparable to composite valve+graft techniques and isolated aortic valve
      replacement, in which the operative mortality approximates 3.3-4%. Long-term
      results are good to excellent and spare the patient anticoagulation and
      prosthetic valve disease.

PMID- 14643806
TI  - Long term follow-up of left ventricular performance and size of the great
      arteries before and after one- and two-stage arterial switch operation of simple
      transposition.
AB  - OBJECTIVE: Long-term angiographic evaluation of left ventricular performance and
      size of the great arteries after one-stage neonatal versus two-stage arterial
      switch operation (ASO) of simple transposition. METHODS: Analysis of
      cineangiographic studies obtained during the process of two-stage ASO for 34
      patients and after neonatal repair for 52 patients. RESULTS: At early follow-up
      after two-stage ASO the left ventricular enddiastolic volume (LVEDV) was +1.8
      standard deviations (S.D.) larger than LVEDV of control patients, but normalized
      completely (0.0 S.D.) at late follow-up. In contrast, after neonatal repair the
      LVEDV was always normal, and the median EF was significantly higher than after
      two-stage ASO (73 vs. 68%). The diameters of the native pulmonary annulus and
      sinus increased significantly after pulmonary artery banding to +4.5 and +4.8
      S.D., respectively. After ASO, a significant decrease of the respective sizes
      occurred from early to late follow-up (annulus: +6.0 to +2.1 S.D.; sinus: +7.1 to
      +4.1 S.D.). After neonatal ASO the neoaortic annulus and sinus were only +1.5 and
      +2.7 S.D. larger than the comparable normal structures. The differences to the
      two-stage group were significant. In both groups, the neoaortic anastomosis had
      no diameters significantly different from normal. After one- and two-stage
      repair, the size of the neopulmonary annulus and sinus decreased similarly in
      both groups from early to late follow-up (annulus +0.9 to -2.4 S.D.; +0.3 to -2.8
      S.D.; sinus: -0.7 to -1.6 S.D.; -0.7 to -1.8 S.D.). CONCLUSIONS: Neonatal ASO has
      definite advantages over two-stage repair concerning LV-performance and the
      degree of dilation of the neoaortic root. The significantly reduced size of the
      neopulmonary root after both procedures is remarkable, but fortunately mostly
      without clinical significance.

PMID- 14643807
TI  - Bioartificial grafts for transmural myocardial restoration: a new cardiovascular
      tissue culture concept.
AB  - OBJECTIVE: Survival of bioartificial grafts that are destined to restore cardiac
      function stands and falls with their nutrient supply. Engineering of myocardial
      tissue is limited because of lack of vascularization. We introduce a new concept
      to obtain bioartificial myocardial grafts in which perfusion by a macroscopic
      core vessel is simulated. METHODS: We have designed an experimental reactor with
      multiple chambers for the production of bioartificial tissue or tissue
      precursors. By introduction of in- and output lines of distinct diameter and
      insertion of a core vessel into each chamber, we established pulsatile,
      continuous flow through the embodied three-dimensional tissue culture. In the
      present study, collagen components served as the ground matrix wherein neonatal
      rat cardiomyocytes were inoculated. For the assessment of cellular viability and
      distribution in comparison to static, non-perfused culture, fluor-desoxy-glucose
      positron-emission-tomography and life/dead assays were employed. RESULTS: We
      obtained 3D constructs of 8-mm thickness, which display high viability and
      metabolism (6.0+/-1.3(e-03) in the perfused vs. 4.0+/-0.3(e-03) in the unperfused
      chambers). The core vessel has the size of a human coronary and remained patent
      during the entire culture process. We observed centripetal migration of the
      embedded cardiomyocytes to the site of the core vessel. Cardiomyocytes partially
      resumed a spindle like form without additional stretch. CONCLUSIONS: The present
      dynamic tissue culture concept is highly effective in manufacturing thick, viable
      grafts for cardiac muscle restoration, which could be surgically anastomosable.
      The bioreactor may accommodate multiple types of cells and tissues for
      innumerable in vitro and in vivo applications.

PMID- 14643808
TI  - Effects of increased afterload on left ventricular performance and mechanical
      efficiency are not baroreflex-mediated.
AB  - OBJECTIVE: To assess baroreflex intervention during increase in left ventricular
      afterload, we compared the effects of aortic banding on the intact cardiovascular
      system and under hexamethonium infusion. METHODS: Six open-chest pigs,
      instrumented for measurement of aortic pressure and flow, left ventricular
      pressure and volume, were studied under pentobarbital-sufentanil anesthesia.
      Vascular arterial properties were estimated with a four-element windkessel model.
      Left ventricular contractility was assessed by the slope of end-systolic pressure
      volume relationship. RESULTS: The effects of aortic banding on mechanical aortic
      properties were unaffected by autonomic nervous system inhibition. However,
      increase in peripheral arterial vascular resistance and in heart rate were
      prevented by hexamethonium. Aortic banding increased left ventricular
      contractility and stroke work. Left ventricular-arterial coupling remained
      unchanged, but mechanical efficiency was impaired. These ventricular changes were
      independent of baroreflex integrity. CONCLUSIONS: Our results demonstrate that an
      augmentation in afterload has a composite effect on left ventricular function.
      Left ventricular performance is increased, as demonstrated by increase in
      contractility and stroke work, but mechanical efficiency is decreased. These
      changes are observed independently of baroreflex integrity. Such mechanisms of
      autoregulation, independent of the autonomic nervous system, are of paramount
      importance in heart transplant patients.

PMID- 14643809
TI  - A pressure overload model to track the molecular biology of heart failure.
AB  - OBJECTIVES: Pressure overload plays an important role in left ventricular
      remodelling and the development of heart failure. The underlying molecular
      mechanisms behind these processes are poorly understood at the myocyte level. To
      investigate this, we developed an ovine model of pressure overload-induced heart
      failure, in which serial left ventricular biopsies were obtained. METHODS: Adult
      male sheep were chronically banded with a novel variable aortic constriction
      device. This was progressively inflated via a subcutaneous port to increase left
      ventricular afterload. The animals were monitored clinically and
      echocardiographically. Serial left ventricular endomyocardial biopsies were
      obtained via the right external carotid artery under fluoroscopic guidance. They
      were used to measure mRNA expression of the genetic regulators of apoptosis by
      reverse transcription polymerase chain reaction. In a subset of the animals, once
      left ventricular failure had been established, the constriction device was
      deflated to produce unloading of the left ventricle. RESULTS: Ten of the 17 sheep
      banded developed left ventricular failure. Over the first 3-4 weeks, left
      ventricular mass index increased acutely (88+/-18 vs. 44+/-10 g/m(2), P<0.01)
      followed by gradual left ventricular dilatation (diastolic left ventricular
      internal diameter 4.1+/-0.7 vs. 3.2+/-0.3 cm, P<0.01). Ventricular function
      remained stable until 7-8 weeks postoperatively, when there was significant
      deterioration (fractional shortening 17+/-8 vs. 40+/-8%, P<0.01) associated with
      clinical heart failure. Expression of the pro-apoptotic genes (bax and Fas)
      increased significantly following inflation of the constriction device and
      persisted through the transition to left ventricular failure. Following deflation
      of the constriction device, myocardial contractility gradually improved over a 3
      week period (fractional shortening 32+/-1 vs. 17+/-8%). CONCLUSIONS:
      Progressively increasing the afterload on the left ventricle produces a clinical
      and echocardiographical picture of chronic heart failure. Obtaining myocardial
      tissue during this transition will allow the molecular correlates of pressure
      overload-induced heart failure and potential myocardial recovery to be
      investigated.

PMID- 14643810
TI  - Distal thoracic aorta hemodynamics during exercise with continuous flow left
      ventricular assist system.
AB  - OBJECTIVES: Continuous flow left ventricular assist systems (LVAS) are being
      discussed as a destination therapy. LVAS patients will have expanded activity of
      daily life, including exercise. In this study, we analyzed the effects of
      exercise on blood flow in the distal thoracic aorta of LVAD implanted animals.
      METHODS: Five calves with a continuous flow LVAS exercised on treadmill at two
      different pump flow rates (PFR), 60-80% (high PFR) and 25-30% (low PFR) of
      pulmonary artery flow rate. Pump, pulmonary artery and descending thoracic aorta
      flow waves were recorded before, during and after exercise. Systolic and
      diastolic flow volume in each cardiac cycle in pump and descending thoracic aorta
      flow was calculated. RESULTS: (1) Average flow rates - Pulmonary artery and
      descending thoracic aorta flow rates increased with heart rate during exercise
      and there was no difference between groups. (2) Pump flow wave - Pump
      regurgitation increased temporally during exercise at both PFRs, but sustained
      incidences of regurgitation after exercise were only observed at low PFR.
      Systolic and diastolic pump flow volume decreased during exercise at both PFRs,
      but systolic volume increased and diastolic volume decreased significantly after
      exercise at low PFR. (3) Descending thoracic aorta flow wave - At high PFR,
      systolic volume of descending thoracic aorta increased but diastolic flow volume
      decreased during exercise. At low PFR, both systolic and diastolic volume of the
      descending thoracic aorta decreased during exercise, but systolic volume
      increased and diastolic volume decreased after exercise. Systolic volume of the
      descending thoracic aorta in low PFR was significantly greater and diastolic
      volume was less than those in high PFR during and after exercise. CONCLUSION:
      Exercise temporarily increases pump regurgitation with continuous flow LVAS
      support. Average flow rate of the descending thoracic aorta was maintained by
      compensation from increased heart rate, although the diastolic flow of the
      descending thoracic aorta decreased after exercise at the lower pump flow rate.
      Further study will be needed to evaluate whether or not this flow decrease causes
      hemodynamic and/or an oxygen delivery mismatch to peripheral tissue.

PMID- 14643812
TI  - Repair of post-infarct ventricular septal defect with or without coronary artery
      bypass grafting in the northwest of England: a 5-year multi-institutional
      experience.
AB  - OBJECTIVE: To present the 5-year experience of the northwest of England's
      surgical repair of post myocardial infarction (MI) ventricular septal defects
      (VSD). Our primary aim was to evaluate the effect of concomitant coronary artery
      bypass grafting (CABG) on mid-term survival and also to identify prognostic
      indicators. METHODS: A multi-centre regional observational study involving
      clinical data from 65 consecutive patients who underwent post MI VSD repair in
      the northwest of England between April 1997 and March 2002. Both prospective and
      retrospective collection of preoperative, operative and postoperative information
      was performed. Patient follow-up was performed by linking their records to the
      National Strategic Tracing Service database. Multivariate logistic regression and
      Cox proportional hazards analyses were used to identify independent risk factors
      for poor prognosis. RESULTS: Of the 65 patients included in the study, 42 (64.6%)
      underwent concomitant CABG with a median of two grafts. The majority of patients
      who had their coronary arteries grafted had multivessel disease (92.9%). Overall
      30-day mortality was 23.1%. Predictors of poor prognosis included preoperative
      inotropes (P<0.001) and total occlusion of infarct related artery (P=0.03). The
      crude hazard ratio (HR) of mid-term mortality for concomitant CABG patients was
      0.82 [95% confidence interval (CI) 0.38-1.78; P=0.62]. After adjustment for
      differences in patient and disease characteristics, the adjusted HR of mid-term
      mortality for concomitant CABG patients was 0.17 (95% CI 0.04-0.74; P=0.019). The
      adjusted freedom from death in the concomitant CABG patients at 30 days, 1, 2,
      and 4 years was 96.2%, 91.6%, 88.8%, and 82.8%, respectively, compared with
      79.1%, 58.8%, 49.1%, and 32.2% for the non-concomitant CABG patients. CONCLUSION:
      These data provide evidence that concomitant CABG is significantly beneficial to
      mid-term mortality rates. We recommend that patients who present with post MI VSD
      who have multivessel disease should be routinely revascularised.

PMID- 14643811
TI  - Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the
      acute phase of human cardiac transplantation.
AB  - OBJECTIVE: Solid organ transplantation is associated with activation of apoptotic
      pathways and other stress markers. We aimed to describe the expression of Bax,
      Bcl-2, iNOs and Hsp-70 in the endothelium and myocytes of both ventricles and to
      see if there is any relationship with clinical donor organ failure. METHODS:
      Twelve patients undergoing heart or heart-lung transplantation (including three
      domino cases) were studied with transmural biopsies from the right (RV) and the
      left ventricles (LV) at the following points: after donor optimisation; at the
      end of ischaemic time; and after 10 min of reperfusion. The 1-week endomyocardial
      RV biopsy was also examined. Five donor hearts turned down purely on functional
      grounds were analysed also. RESULTS: There was no difference between the RV and
      the LV for any of the markers at intraoperative assessment. The pattern of
      expression was not predictive of allograft failure. Donor hearts, however, have a
      strong pro-apoptotic phenotype, which is largely unopposed by the protective
      factors Bcl-2 and Hsp-70. Furthermore, the intensity of myocyte staining
      increases over time for Bax (P<0.001) and iNOs (P=0.02). Domino hearts showed a
      similar pattern. Compared to usable organs, poorly functioning donor hearts have
      stronger myocardial staining for Bax (P=0.002) and iNOs (P=0.01). CONCLUSIONS:
      Clinical cardiac transplantation is associated with activation of the Bax and
      iNOs pathways in both ventricles. The myocardium is affected in time-dependent
      fashion but this is compatible, to a certain extent, with satisfactory allograft
      function. Donor hearts turned down on the basis of poor haemodynamic performance
      have significantly higher expression of Bax and iNOs.

PMID- 14643813
TI  - Safe evolution towards routine off-pump coronary artery bypass: negotiating the
      learning curve.
AB  - OBJECTIVE: Off-pump coronary artery bypass (OPCAB) hopes to avoid morbidity
      associated with cardiopulmonary bypass, improving clinical outcomes. Yet its
      technical difficulty and unfamiliarity raise concern that adoption of OPCAB might
      be associated with poorer outcomes during each surgeon's 'learning curve'. We
      examined trends in patient selection over time as a single surgeon's practice
      evolved to routine OPCAB. METHODS: Between 10-1-96 and 12-31-01, 1479 consecutive
      patients had isolated coronary artery bypass grafting (CABG). Clinical data were
      gathered prospectively and reviewed retrospectively. Trends in adoption of OPCAB
      and clinical outcomes were examined. RESULTS: There were 756 OPCAB and 723
      CABG/cardiopulmonary bypass patients. The practice evolved from 90% conventional
      CABG to 93% OPCAB. An abrupt transition coincided with evolution of techniques to
      expose the obtuse marginal arteries, and improvements in suction-based coronary
      stabilizers. Mortality was 1.0% for the off-pump group and 2.1% for the on-pump
      group. Careful patient selection helped maintain acceptable outcomes during the
      'learning curve'. Patients with depressed left ventricular ejection fraction,
      left main disease, and complex three vessel disease were excluded from OPCAB
      until significant experience (>200 cases) was attained. Presently, all isolated
      coronary bypass cases are candidates for OPCAB except patients with ischemic
      ventricular arrhythmias, those in cardiac arrest, and those for whom previous
      left pneumonectomy or deep pectus excavatum prevent rightward mobilization of
      heart. CONCLUSIONS: Despite a significant learning curve, evolution to routine
      OPCAB can be achieved while maintaining good patient outcomes. The development of
      specialized techniques, coronary stabilizers, and apical suction devices allows
      the application of OPCAB to virtually all coronary bypass patients, as surgeon
      experience matures.

PMID- 14643814
TI  - Myocardial revascularization with and without cardiopulmonary bypass: advantages,
      disadvantages and similarities.
AB  - OBJECTIVES: Off-pump coronary artery bypass surgery is becoming increasingly
      popular although its effectiveness remains controversial. Our goal was to
      investigate the effectiveness of on-pump and off-pump coronary artery bypass
      surgery on early (30 days) and long-term (5 years) clinical outcome in two groups
      of patients selected using propensity scores. METHODS: From November 1994 to
      December 2001, 4381 patients underwent isolated coronary surgery. Applying
      propensity score matching, 1922 patients were selected (off-pump n=961, on-pump
      n=961). RESULTS: Stepwise logistic regression analysis showed that the use of
      cardiopulmonary bypass was an independent predictor for early death, cerebral
      vascular accident, early negative primary endpoints (ENPEP), and early major
      events (EME). Five years freedom from both events was similar in the two groups.
      However, freedom from acute myocardial infarction (AMI) in grafted areas was
      higher in the off-pump than in the on-pump patients, a possible explanation being
      the lower postoperative creatine kinase myocardial band (CKMB) release. Grouping
      all patients according to CKMB peak release also showed that patients with normal
      release values had higher freedom from all cardiac events investigated. A
      subgroup analysis of 59 patients converted from off-pump to on-pump showed higher
      early mortality, ENPEP, and EME. Conversion, however, did not affect late
      clinical outcome. CONCLUSIONS: These results suggest that off-pump surgery
      reduces early mortality and morbidity. Conversion to on-pump carries high in
      hospital mortality and morbidity. Long-term clinical outcome is similar in the
      two groups; however, off-pump patients seemed to have a higher freedom from AMI
      in the grafted area which might be related to the lower CKMB peak release when
      compared with patients undergoing on-pump surgery.

PMID- 14643815
TI  - Real-time patency control with thermal coronary angiography in 1401 coronary
      artery bypass grafting patients.
AB  - OBJECTIVE: Intraoperative coronary angiography has always been favoured by
      cardiac surgeons. Thermal coronary angiography (TCA) is a useful method for
      intraoperative control of graft patency. It detects heat differences between
      tissues, provides easy-to-interpret angiographic images and even measures the
      flow of the grafts quantitatively. METHODS: Between January 2000 and January
      2002, TCA has been used in scheduled coronary bypass operations. Upon completion
      of each distal anastomosis, the perfusion of the distal arterial tree from the
      graft was evaluated with a thermal camera. RESULTS: TCA was applied to 1401
      patients, mean age 60.97+/-9.61 years, who underwent simple coronary artery
      bypass grafting (CABG) procedures. A total of 4105 thermal images were obtained
      including 2161 venous, 1355 single internal thoracic artery (ITA), 56 bilateral
      ITA and 477 radial artery grafts. Image quality was not sufficient in 34 grafts
      (1.57%) due to either deep intramyocardial vessels or excessive epicardial fat
      tissue. Technical failures in three ITA anastomoses were detected and revised
      before the cross-clamp was removed. Flow-restricting lesions distal to the
      anastomosis on the left anterior descending artery (LAD) in nine patients were
      managed with a secondary distal bypass graft (five patients) or plaque splitting
      and anastomotic revision (four patients). Endarterectomy was combined in seven
      patients since the graft flow and the distal visualization was not satisfactory,
      although the anastomoses were performed on a good lumen. Angiographically
      undetected diagonal arteries were revascularized in 11 patients with totally
      occluded LAD vessels. CONCLUSION: Thermal imaging provides decisive coronary
      angiographies, and detects the perfusion area and flow of the implanted graft. It
      allows real-time detection of technical failures, reveals unexpected occluding
      plaques or any kind of flow-restricting lesions, and gives the chance of
      refinement of the anastomosis during the arrest period. We believe that the
      thermal imaging technique is a safe, noninvasive and feasible method to document
      the quality of the myocardial revascularization intraoperatively.

PMID- 14643816
TI  - Novel pharmacological preconditioning with diazoxide attenuates myocardial
      stunning in coronary artery bypass grafting.
AB  - OBJECTIVE: To investigate whether novel pharmacological preconditioning with
      diazoxide could protect the myocardial function and decrease myocardial injury in
      patients undergoing coronary artery bypass grafting (CABG). METHODS: Forty
      patients with stable angina who were scheduled for isolated elective CABG
      operations were randomized into control group (n=20) and diazoxide (DZX) group
      (n=20). In the DZX group, 1.5 mg/kg diazoxide was infused intravenously within 5
      min followed by a 5-min washout before commencing the cardiopulmonary bypass
      (CPB). In the control group, a time-matched period of placebo infusion was given.
      Hemodynamic data and biochemical markers of myocardial injury were measured
      perioperatively. RESULTS: There were no adverse effects related to diazoxide.
      Cardiac index (CI) increased postoperatively as compared with baseline. In the
      DZX group, the improvement of CI was better than that in the control group
      (p=0.001). Left and right ventricular stroke work indexes decreased
      postoperatively, and recovered much faster in the DZX group (p=0.027 and p=0.049,
      respectively). There were no statistically significant differences in the other
      hemodynamic parameters. The creatine kinase cardiac isoenzyme (CK-MB) was highest
      in both groups on the first postoperative day (control 28.8+/-23.8 and DZX 27.3+/
      19.4, N.S.). The cumulative release of CK-MB postoperatively was lower in the DZX
      patients as compared with the controls, but the difference remained not
      significant (p=0.09). CONCLUSIONS: Pharmacological preconditioning of the human
      heart with diazoxide is feasible; it confers additional myocardial protection
      beyond that provided by the cardioplegia alone by attenuating myocardial stunning
      after CABG operations.

PMID- 14643817
TI  - Effect of low [CaCl2] and high [MgCl2] cardioplegia and moderate hypothermic
      ischemia on myoplasmic [Ca2+] and cardiac function in intact hearts.
AB  - OBJECTIVE: Cold cardioplegia (CP) protects against ischemic damage in part by
      reducing [Ca(2+)](i) overload on reperfusion. Hyperkalemic cardioplegic solutions
      are widely used in coronary artery bypass procedures, and the specific ionic
      composition of these solutions may contribute to their variable myocardial
      protective effects secondary to reduced Ca(2+)(i) loading. We reported previously
      that CP decreased the rise in cardiac diastolic (dia) [Ca(2+)](i) observed during
      4 h cold storage at 3 degrees C in Krebs-Ringer's (KR) solution and decreased
      dia[Ca(2+)](i) and increased systolic (sys) [Ca(2+)](i) and function on
      reperfusion after cold storage. Our aim here was to determine if low Ca(2+)(o)
      and high Mg(2+)(o) adds to the protective effects of high K(+)(o) by decreasing
      [Ca(2+)](i) during ischemia and reperfusion. METHODS: We compared effects of 4.5
      mM K(+)(o), 2.5 mM Ca(2+)(o) and 2.4 mM Mg(2+)(o) KR solution with a higher
      K(+)(o) (18 mM), a lower Ca(2+)(o) (1.25 mM) and/or higher Mg(2+)(o) (7.2 mM) CP
      solutions on cardiac mechanic function and sys and dia[Ca(2+)](i) during and
      after moderate hypothermic global ischemia (17 degrees C for 4 h) in guinea pig
      intact hearts isolated by the Langendorff technique. Isovolumetric left
      ventricular pressure (LVP) was measured with a transducer connected to a fluid
      filled balloon placed in the LV and [Ca(2+)](i) was measured using indo-1
      fluorescence and a fiberoptic cable placed on the LV free wall. RESULTS: For all
      CP groups compared to the KR control group after 60 min reperfusion, we observed
      significant lowering of dia[Ca(2+)](i) by 47%, left ventricular diastolic
      pressure (diaLVP) by 55%, and infarct size by 43%. We also found significant
      elevation of sys[Ca(2+)](i) by 25%, d[Ca(2+)](i)/dt(max) and d[Ca(2+)](i)/dt(min)
      by 33 and 34%, sys-diaLVP by 55%, dLVP/dt(max) and dLVP/dt(min) by 34 and 40%,
      coronary flow by 31%, cardiac efficiency by 21%, and MVO(2) by 25%. These results
      indicate that CP reduces myoplasmic Ca(2+) loading and improves mechanical and
      metabolic function on warm reperfusion compared to KR. However, there were no
      differences in these indices of Ca(2+)(i) cardiac function or metabolism among
      any CP group after warm reperfusion with KR solution. CONCLUSION: Increasing
      K(+)(o) to produce cardiac arrest was the most cardioprotective effect of CP
      against ischemia reperfusion injury; lowering Ca(2+)(o) or raising Mg(2+)(o) did
      not add to this protective effect or additionally alter [Ca(2+)](i).

PMID- 14643818
TI  - Myocardial protection in adult cardiac surgery: current options and future
      challenges.
AB  - Current techniques of myocardial protection are evolving with the use of less
      conventional modalities of cardioplegia and have reduced the morbidity and
      mortality of cardiac operations. Blood cardioplegic solutions appear superior to
      cold cardioplegia in terms of myocardial protection and adjuncts as
      glutamate/aspartate enhancement, antioxidant supplementation, nitric oxide donors
      and maintenance of calcium homeostasis seem effective. In the near future,
      further experimental and clinical investigations about pharmacological
      preconditioning, sodium-hydrogen exchangers inhibition and gene therapy need to
      be addressed to well define their potential role in the improvement of current
      techniques of myocardial protection that are suboptimal in high-risk clinical
      settings.

PMID- 14643819
TI  - Long-term results of pathological stage I non-small cell lung cancer: validation
      of using the number of totally removed lymph nodes as a staging control.
AB  - OBJECTIVE: The number of totally removed lymph nodes during thoracotomy was used
      alternatively to represent the quality of lymphadenectomy in patients with
      pathologic stage I non-small cell lung cancer (NSCLC). We combined this new
      parameter with other well-established prognostic factors and performed
      multivariate survival analyses to validate its usage as a stage control. METHODS:
      Three hundred and twenty-one patients who underwent complete surgical resection
      for stage I NSCLC were reviewed retrospectively. Aside from the number of lymph
      nodes removed during thoracotomy, other well-known clinical and histopathological
      factors were also included as possible prognostic factors for analysis. Two
      survival analyses, overall death and cancer-related death as study end-point,
      were performed, using the Kaplan-Meier method and multivariable Cox's
      proportional hazard regression analysis. Stepwise method of variable selection
      was employed to choose the 'best' Cox proportional hazard model in each survival
      analysis. RESULTS: The overall 5- and 10-year survival rates were 48 and 35%, and
      the cancer-related 5- and 10-year survival rate was 63.3 and 58.3%, respectively.
      The number of totally removed lymph nodes during thoracotomy, tumor size and
      smoking history in multivariable analysis significantly affected both overall and
      cancer-related survival rates. Cell type of adenocarcinoma or large cell
      carcinoma was associated with a worse cancer-related survival compared with other
      histological types. CONCLUSIONS: The quality of lymphadenectomy, represented
      quantitatively by the number of totally removed lymph nodes during thoracotomy,
      may impact on a more accurate tumor stage, and will affect the survival rate for
      patients with stage I NSCLC as well as other well known clinical and
      histopathological factors.

PMID- 14643820
TI  - Long term results of surgery versus continuous hyperfractionated accelerated
      radiotherapy (CHART) in patients aged >70 years with stage 1 non-small cell lung
      cancer.
AB  - BACKGROUND: Patients with T1N0 non-small cell lung cancer (NSCLC) are preferably
      treated by anatomic lobectomy. However, not all such patients are suitable for
      lobectomy due to their age or co-morbidity. Our aim was to determine the results
      obtained following lobectomy, wedge resection (WR) or continuous
      hyperfractionated accelerated radiotherapy (CHART) in patients aged >70 years.
      PATIENTS: Two hundred and fifteen consecutive patients aged >70 years, with
      pathologic stage 1 NSCLC in our unit between 1991 and 2001 were studied. Of these
      patients, 149 had a lobectomy, 47 had a WR and 19 had CHART. Follow-up was 100%
      complete. RESULTS: Analysis demonstrated the WR and CHART patients to have
      reduced pulmonary function (FEV(1) 59% and 52%, respectively, of predicted vs.
      76%, P<0.001) when compared to the lobectomy group but there were no differences
      among the groups with regard to mean age and histologic tumour type. There were
      no operative mortality among patients after WR; however, a 2.7% 30-day operative
      mortality among patients undergoing lobectomy (P=0.29). Kaplan-Meier survival
      curves at 1 and 5 years for patients undergoing WR, lobectomy and CHART was 98%
      and 74% vs. 97% and 68% vs. 80% and 39%, respectively (P=0.0484). The frequency
      of local/regional recurrence in the WR group (19.1%) was not significantly higher
      than in the lobectomy group (18.4%, P=0.38) when compared to the CHART group
      (27%, P=0.07). CONCLUSION: Loco-regional recurrence and survival after WR and
      lobectomy in elderly patients with stage I NSCLC are comparable. Although the
      numbers are small, these data suggest that CHART is a reasonable treatment option
      for those who are not suitable candidates for surgery.

PMID- 14643821
TI  - Surgical feasibility of ipsilateral multifocal non-small cell lung cancer in
      different lobes: excellent survival in node-negative subgroup.
AB  - OBJECTIVE: The management of ipsilateral multifocal non-small cell lung cancer
      (NSCLC) in different lobes is still controversial. We analyzed our surgical
      results and the prognostic factors with the findings of other studies and
      evaluated the surgical feasibility. METHODS: Between January 1, 1983 and December
      31, 2001, 1408 patients underwent operation for primary NSCLC, including 20
      patients who received complete resections for multifocal NSCLC of the same
      histological type in ipsilateral different lobes. RESULTS: The 1-, 2- and 5-year
      survival rate of the 20 patients were 60.0, 39.3 and 28.1%, respectively. There
      were no statistically significant differences in T-status, gender, pathological
      type, and stage. An excellent 5-year survival rate of 66.7% (median, 101 months)
      in the group without node involvement was found (N0 vs. N1+2, P=0.0872).
      CONCLUSION: Our data suggest that surgical resection is mandatory in patients
      with ipsilateral multifocal NSCLC when there is no evidence of node metastasis.

PMID- 14643822
TI  - Results of surgical treatment of T4 non-small cell lung cancer.
AB  - OBJECTIVE: Because of location and invasion of surrounding structures, the role
      of surgical treatment for T4 tumors remains unclear. Extended resections carry a
      high mortality and should be restricted for selected patients. This study
      clarifies the selection process in non-small cell T4 tumors with invasion of the
      mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral
      body, and carina, or with malignant pleural effusion. METHODS: From 1977 through
      1993, 89 patients underwent resection for primary non-small cell T4 carcinomas.
      Resection was regarded as complete in 34 patients (38.2%) and incomplete in 55
      patients (61.8%). Actuarial survival time was calculated and risk factors for
      late death were identified. RESULTS: Overall hospital mortality was 19.1% (n=17).
      Mean 5-year survival was 23.6% for all hospital survivors, 46.2% for patients
      with complete resection and 10.9% for patients with incomplete resection
      (P=0.0009). In patients with complete resection, mean 5-year survival for
      patients with invasion of great vessels was 35.7%, whereas mean 5-year survival
      for invasion of other structures was 58.3% (P=0.05). Age, mediastinal lymph node
      involvement, type of operative procedure, and postoperative radiotherapy did not
      significantly influence survival. CONCLUSION: In certain T4 tumors complete
      resection is possible, resulting in good mean 5-year survival especially for
      tumors with invasion of the trachea or carina. High hospital mortality makes
      careful patient selection imperative.

PMID- 14643823
TI  - Is there a role for pre-operative contrast-enhanced magnetic resonance imaging
      for radical surgery in malignant pleural mesothelioma?
AB  - OBJECTIVE: To assess the use of contrast-enhanced magnetic resonance imaging
      (CEMRI) in addition to computed tomography in the pre-operative assessment of
      patients for radical surgery in malignant pleural mesothelioma. METHODS: Over a
      45-month period, 51 of 76 patients assessed (69 men and seven women), underwent
      extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative
      pathological stage was correlated with radiological staging, with particular
      emphasis on tumour resectability. RESULTS: Seventeen (22%) patients were found on
      CEMRI to have unresectable, but histologically unconfirmed disease, not
      previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but
      pathological nodal data were incomplete in three, so excluding these patients
      from further analyses. The median pre-operative interval after CEMRI was 17 days.
      Two patients were found to have unexpectedly extensive disease at thoracotomy,
      thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the
      International Mesothelioma Interest Group system, tumour stage was correctly
      predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely
      due to the underestimation of pericardial involvement, but this did not affect
      resectability and had no significant effect on prognosis. Nodal stage was
      correctly identified in 60% of patients. CEMRI was successful in predicting
      pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%),
      but less so in identifying tumour stage T2 or less (sensitivity of 23%;
      specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%).
      CONCLUSIONS: CEMRI is most useful in the differentiation of T3 and T4 disease and
      may be unnecessary at earlier stages. Its multiplanar tumour localisation
      abilities are of value in the assessment of resectability. It is unlikely to
      contribute significantly to nodal staging, but it remains a valuable adjunct in
      the selection of patients for radical surgery.

PMID- 14643824
TI  - Horner's syndrome as a complication in thoracic surgical practice.
AB  - OBJECTIVE: To determine the incidence, reasons and prognosis about Horner's
      syndrome in thoracic surgical patients. METHODS: In this prospective clinical
      study, 933 adult patients were assessed between the years of 1998 and 2002. All
      patients who underwent chest tube insertion (n: 662 patients) or thoracotomy (n:
      342 patients), or who had thoracic trauma (n: 268 patients) were routinely
      examined to detect of Horner's syndrome. The patients with Horner's syndrome due
      to the invasion of malignant tumour to sympathetic chain were not included in the
      study. RESULTS: Horner's syndrome was detected in twelve patients from these 933
      patients (1.3%). The considered etiologic factors were chest tube pressure in
      five patients, operative complication in two patients and trauma in five
      patients. In patients with chest tube pressure were fully recovered from Horner's
      syndrome but the remaining did not. CONCLUSIONS: Malposition of the chest tube is
      an important aetiological factor of Horner's syndrome, and it is reversible if
      the tube position is corrected urgently.

PMID- 14643825
TI  - Giant thymoma.

PMID- 14643826
TI  - Giant schwannoma of the posterior mediastinum.

PMID- 14643827
TI  - A huge intrathoracal mass in a 1-year-old infant: an inflammatory myofibroblastic
      tumor.

PMID- 14643828
TI  - Bilateral giant pulmonary artery aneurysms early in Behcet's disease.

PMID- 14643829
TI  - Giant retroaortic coronary artery bypass graft aneurysm.

PMID- 14643830
TI  - Rupture of abdominal aortic aneurysm into duodenum.

PMID- 14643831
TI  - Sternal sinus 17 years after a Bentall procedure.

PMID- 14643832
TI  - Spontaneous rupture of the left pulmonary artery-caused by long-term steroid use?
AB  - We describe a 71-year-old woman with spontaneous rupture of the left pulmonary
      artery. She was admitted with pulselessness of her left arm and lack of
      sensibility in her left arm and leg. Echocardiography and thoracic CT did not
      confirm aortic dissection. CT only showed hematoma around the descending aorta.
      She underwent left-sided thoracotomy. Intraoperatively, a rupture of the left
      pulmonary artery without any evidence of an aneurysm was found. Potentially
      predisposing factors for this rupture were long-term use of steroids due to COPD
      and her age.

PMID- 14643833
TI  - Uhl's anomaly complicated with critical ventricular arrhythmia in a 2-month-old
      infant.
AB  - We report a case of Uhl's anomaly in a 2-month-old infant who presented with
      critical ventricular arrhythmia. The patient underwent a successfully surgical
      repair by semitotal resection of the right ventricle free wall, tricuspid
      annuloplasty, and one and one-half ventricular repair.

PMID- 14643834
TI  - Boxer's pericardium.
AB  - A 65-year-old retired professional boxer presented with progressively worsening
      shortness of breath, peripheral oedema and mild abdominal swelling over a period
      of 6 months. His only past medical history was hypertension. Subsequent
      investigations revealed chylous ascites, pericardial constriction and bilateral
      chylothorax. He had uneventful pericardectomy, and post-operatively the
      chylothorax resolved only after administration of octreotide for 10 days. The
      histopathological features of fibrosis, haemosiderin deposition in the
      pericardium and abundant haemosiderin-laden macrophages are consistent with
      chronic resolving haemopericardium. These findings suggested that the cause of
      pericardial constriction was repeated chest trauma from boxing.

PMID- 14643835
TI  - Superior mesenteric artery stenting to augment splenorenal arterial bypass for
      intractable complex renovascular hypertension.
AB  - An alternative source of visceral arterial inflow is sometimes necessary for
      renal revascularization when aortorenal endarterectomy or bypass is inappropriate
      due to severely diseased aorta. We report the case of a 46-year-old male with
      recurrent intractable renovascular hypertension in renal failure secondary to
      occlusion of the celiac axis due to progression of aortoarteritis following
      splenorenal arterial bypass performed 5 years before. Aortogram visualized
      intestinal arterial arcade supporting patent bypass with critically stenosed
      superior mesenteric artery. Successful angioplasty with stenting of superior
      mesenteric artery restored adequate renal flow through the bypass leading to
      recovery and easy control of hypertension.

PMID- 14643837
TI  - Prior exposure to phencyclidine decreases voluntary sucrose consumption and
      operant performance for food reward.
AB  - Prior exposure to the psychotomimetic drug phencyclidine (PCP) produces a number
      of schizophrenia-like behaviors in animals. The goal of the present study was to
      determine whether prior exposure to PCP produces decreased reward function,
      thereby modeling one aspect of negative schizophrenic symptomatology. To this
      aim, the consequences of prior exposure to PCP were assessed on two types of
      appetitive consumptive behavior. In the first set of experiments, the effects of
      PCP (15 mg/kg, 20 h before testing) on sucrose consumption were tested for three
      consecutive days under conditions of deprivation and nondeprivation. In the
      deprivation condition, animals were water deprived for 4 h prior to injection of
      PCP or saline (SAL). Twenty hours following the injection (24 h after the onset
      of water deprivation), animals were allowed access to either 5% sucrose or water
      for 30 min. In the nondeprivation condition, 5% sucrose consumption was measured
      for 30 min, 20 h after PCP or SAL injection and water consumption was measured
      during the 23.5 h preceding sucrose consumption. PCP decreased both sucrose and
      water consumption under deprivation conditions on the second and third day of
      testing but selectively decreased sucrose consumption under nondeprivation
      conditions on all three testing days. LiCl (50 mg/kg, 20 h before testing) did
      not significantly reduce sucrose consumption in the nondeprivation paradigm,
      indicating that the effect of PCP was not due to conditioned taste aversion. In
      the second experiment, PCP (15 mg/kg, 20 h before testing) decreased operant
      performance when animals were switched from a continuous reinforcement schedule
      of food delivery to a fixed ratio (FR4) schedule. Apomorphine (APO, 30 microg/kg,
      30 min before testing), a positive control, induced a similar performance
      deficit. However, the PCP-induced deficit was not apparent until the third day of
      FR4 testing while the APO deficit was apparent on the first day. The effects of
      PCP on sucrose consumption demonstrate PCP-induced decreases in reward function.
      However, the delayed appearance of the PCP-induced decrease in operant
      performance suggests that these results may be better explained by a PCP-induced
      attentional deficit, also characteristic of schizophrenic psychopathology.

PMID- 14643836
TI  - Behavioral and physiological effects of cocaine in humans following triazolam.
AB  - RATIONALE: Cocaine abuse represents a significant public health problem. Gamma
      aminobutyric acid (GABA) agonists may attenuate the behavioral effects of cocaine
      and may be effective pharmacotherapies for cocaine abuse and dependence.
      OBJECTIVES: The aim of this experiment was to determine the combined effects of
      oral cocaine (0 and 300 mg) and triazolam (0 and 0.5 mg), a GABA(A) modulator, in
      10 individuals with recent histories of cocaine use. METHODS: Volunteers received
      each of the four possible drug combinations in mixed order. Drug effects were
      assessed using a battery of subject-rated drug-effect questionnaires and
      physiological indices. RESULTS: Cocaine alone produced prototypical stimulant
      like subject-rated drug effects (e.g., increased ratings of High, Like Drug, and
      Willing to Take Drug Again). Triazolam alone produced sedative-like effects
      (e.g., increased scores on the Pentobarbital, Chlorpromazine, Alcohol Group
      [PCAG] scale of the Addiction Research Center Inventory [ARCI]). Triazolam
      pretreatment did not significantly attenuate the subject-rated effects of
      cocaine. CONCLUSIONS: While the results of this study do not support the utility
      of GABA(A) modulators as pharmacotherapies for cocaine abuse, future research
      should test other benzodiazepines (e.g., alprazolam) using more sophisticated
      methods (e.g., dose-response curves for the drugs alone and in combination) and
      behavioral arrangements (e.g., drug discrimination).

PMID- 14643838
TI  - Amantadine does not modulate reinforcing, subjective, or cardiovascular effects
      of cocaine in humans.
AB  - Data from several clinical studies have suggested that amantadine, which has
      dopaminergic agonist and glutamatergic antagonist effects, may be useful for the
      treatment of cocaine dependence. The interaction between amantadine and smoked
      cocaine was examined in 10 cocaine smokers (7 men, 3 women), who participated in
      a 26-day inpatient study. Participants were maintained on amantadine (0 and 100
      mg bid) for 5 days prior to laboratory testing, using a double-blind crossover
      design. Under each medication condition, participants smoked a sample dose of
      cocaine base (0, 12, 25, and 50 mg) once, and were subsequently given five choice
      opportunities, 14 min apart, to self-administer that dose of cocaine or receive a
      merchandise voucher ($5.00). Each cocaine dose was tested twice under each
      medication condition, and the order of medication condition and cocaine dose
      varied systematically. Cocaine produced stimulant-like reinforcing, subjective,
      and physiological effects. Amantadine maintenance did not modify the choice to
      self-administer smoked cocaine. These findings, taken together with the decidedly
      mixed literature, suggest that amantadine (100 mg bid) will not have a role in
      the treatment of cocaine dependence.

PMID- 14643839
TI  - Effects of donepezil on DOI-induced head twitch response in mice: implications
      for Tourette syndrome.
AB  - Tourette syndrome (TS) is a neurological disorder characterized by persistent
      motor and phonic tics. Administration of the selective 5-HT(2A/2C) agonist 1-(2,
      5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induces head twitches in mice that
      have been proposed to model tics seen in TS. Previous studies have demonstrated
      that nicotine markedly attenuates DOI-induced head twitch response (HTR). This
      and the reports that nicotine may have clinical efficacy in reducing symptoms of
      TS suggest possible involvement of the nicotinic cholinergic system in this
      disorder. Donepezil is an acetylcholinesterase inhibitor approved for use in mild
      to moderate Alzheimer's disease. The purpose of this study was to investigate
      whether donepezil might also reduce DOI-induced HTR, and whether its combination
      with nicotine might result in an additive or synergistic effect. Moreover, to
      elucidate the possible role of nicotinic receptors in this paradigm, the effects
      of mecamylamine, a nicotinic antagonist, was also evaluated. Acute and chronic
      administration of donepezil (0.1 mg/kg) or nicotine (0.5 mg/kg base),
      significantly reduced DOI-induced HTR. No additive or synergistic effects of
      donepezil and nicotine were observed. Acute mecamylamine administration (0.5-5.0
      mg/kg) dose-dependently inhibited DOI-induced HTR. None of the mecamylamine doses
      blocked the inhibitory effects of donepezil or nicotine on DOI-induced HTR. These
      results suggest that donepezil may have therapeutic potential in treating motor
      tic symptoms of TS. Moreover, the action of donepezil and nicotine may be
      mediated through the same mechanism.

PMID- 14643840
TI  - GABAergic agents prevent alpha-melanocyte stimulating hormone induced anxiety and
      anorexia in rats.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) is a hypothalamic peptide
      believed to play a tonic inhibitory role in feeding and energy homeostasis.
      Systemic administration of alpha-MSH is known to produce anorexia and anxiety.
      Since synaptic contacts between gamma-aminobutyric acid (GABA)ergic terminals and
      alpha-MSH neurons in the hypothalamus have been reported, the present work was
      undertaken to refine our knowledge on the role of GABAergic systems in anxiety
      and anorexia induced by intracerebroventricular (icv) administration of alpha-MSH
      in rats. The anxiety was assessed by elevated plus maze, and spontaneous food
      consumption was monitored during dark cycle. Prior administration of diazepam and
      muscimol that promote the function of GABA(A) receptors reversed the anxiogenic
      response and decreased food intake elicited by alpha-MSH. In contrast,
      bicuculline, the GABA(A) receptor antagonist, not only enhanced the effects of
      alpha-MSH but also prevented the influence of GABAergic drugs on alpha-MSH
      induced anorexia and anxiety. These findings suggest that alpha-MSH-induced
      anxiety and anorexia are due to its negative influence on GABAergic system.

PMID- 14643841
TI  - Individual self-administration of nicotine by rats.
AB  - Self-administration (SA) of nicotine (N) was studied in 20 male and 19 female
      N:NIH rats using the two-bottle method. The experimental protocol consisted of
      seven consecutive periods each lasting 6 days: Period (P)1, choice of water (W)
      and 0.003% N; P2, choice of W and 0.006% N; P3, choice of W and 0.012% N; P4, W
      only; P5, choice of W and 0.006% N; P6, 0.006% N only; and P7, choice of W and
      0.006% N. Group means showed that males and female rats consumed similar amounts
      of N during Ps 1-3. After an N-free period (P4), a small decline was observed in
      the subsequent voluntary intake of N (P5). Forced N (P6) exposure did not affect
      a subsequent N intake (P7) in males but increased it slightly in females. A
      survey of individual animals, however, showed that the voluntary N consumption
      varied greatly among animals, but was quite consistent for a particular rat.
      Values ranged from 0.43 to 7.59 for males and from 0.35 to 4.69 mg/kg/day for
      females for Ps 1-3. The N-free (P4) and the forced-N (P6) periods each affected a
      subsequent voluntary N intake (P5, P7) of the rats very differently, but again
      consistently, in that some rats decreased, some increased and some did not change
      their N choice. The results indicate that group means can be misleading in their
      conclusions and strongly support the assumption that the response of an
      individual animal to N, and not N per se, is the determining force of its SA.

PMID- 14643842
TI  - Inhibition mechanism of S-adenosylmethionine-induced movement deficits by
      prenylcysteine analogs.
AB  - We previously showed that S-adenosylmethionine (SAM) induces movement impairments
      similar to those observed in Parkinson's disease (PD) apparently by prenylated
      protein methylation; 5 kDa molecules being methylated and the symptoms being
      inhibited by prenylcysteine (PC) analogs. In the present study, we explore the
      biochemical mechanism of action of the PC analogs. N-acetylgeranylcysteine (AGC),
      N-acetylfarnesylcysteine (AFC), N-acetylgeranylgeranylcysteine (AGGC),
      farnesylthioacetic acid (FTA), farnesyl-2-ethanesulfonic acid (FTE) and
      farnesylsuccinic acid (FMS), but not farnesylthiotriazole (FTT) and
      farnesylthiolactic acid (FTL), inhibited the SAM-induced motor impairments.
      Incubation of the respective analogs with rat brain membranes containing
      prenylated protein methyltransferase (PPMTase) resulted in the methylation of
      AGC, AFC and AGGC. FTA, FTE, FMS and FTT, but not FTL, inhibited the enzyme
      activity. A single injection of the active analogs remained effective for at
      least 3 days against repeated injections of 1 micromol SAM. Amphetamine-induced
      hyperactivity in rats was inhibited by SAM but potentiated by FTE. During 60 min,
      the movement time for amphetamine-treated rats was 1477 s compared with 633 and
      1664 s for amphetamine+SAM- and amphetamine+FTE-treated rats, respectively. The
      total distance for amphetamine+FTE-treated rats was 82% higher than for
      amphetamine. The horizontal activity was 30,728 (amphetamine), 15,430 (FTE),
      18,526 (amphetamine+SAM), 41,736 (amphetamine+FTE) and 7004 (SAM) as compared to
      the PBS control (4726). The intricate relationship between the actions of SAM,
      which speeds up prenylated protein methylation and impairs movement, amphetamine,
      which increases synaptic dopamine levels and movement, and the PC analogs, which
      prevent the SAM-induced movement impairments, suggests a SAM-induced defect on
      dopamine signaling as the likely cause of the symptoms. The data reveal that
      interaction of PC analogs with PPMTase may not be an indicator of anti-PD-like
      activity.

PMID- 14643843
TI  - Clonazepam increases in vivo striatal extracellular glucose in diabetic rats
      after glucose overload.
AB  - Hyperglycemia modulates brain function, including neuronal excitability,
      neurotransmitter release and behavioral changes. There may be connections between
      the GABAergic system, glucose sensing neurons and glucose in the neuronal
      environment that shed light on the mechanism by which GABA(A) agents influence
      depressive behavior in diabetic rats submitted to the forced swimming test. We
      aimed to investigate whether clonazepam (CNZ), a GABA(A) receptor positive
      modulator, modifies in vivo striatal extracellular glucose levels in diabetic
      rats under fasting condition or after oral glucose overload. Streptozotocin
      diabetic and nondiabetic rats were submitted to in vivo striatal microdialysis.
      Perfusate samples were collected at baseline, during fasting and following
      administration of CNZ (0.25 mg/kg) and oral glucose overload. Blood glucose and
      striatal extracellular glucose were measured simultaneously at several time
      points. Fasting striatal glucose levels were higher in diabetic than in
      nondiabetic rats and the differences between these animals were maintained after
      glucose overload. The increases in extracellular striatal glucose after glucose
      overload were around 40% and blood to brain transference was decreased in
      diabetics. CNZ treatment paradoxically increased striatal glucose after glucose
      overload in diabetic rats, which may mark the dysfunction in brain glucose
      homeostasis.

PMID- 14643844
TI  - Neurosteroid consumption has anxiolytic effects in mice.
AB  - The neurosteroids allopregnanolone (ALLOP) and pregnanolone (PREG), like ethanol,
      potentiate gamma-aminobutyric acid(A) receptor function. PREG-hemisuccinate (PREG
      HS) is a negative modulator of N-methyl-D-aspartate (NMDA) receptors. Because
      C57BL/6J (B6) and DBA/2J (D2) mice differ in ethanol preference, voluntary
      consumption of ALLOP and PREG-HS (50 microg/ml solution) versus tap water was
      measured in B6 and D2 mice for a minimum of 8 days. Mice were acclimated to a
      reverse light-dark cycle prior to the initiation of experiments. In the first
      study, both B6 and D2 mice exhibited preference for the PREG-HS solution. In the
      second study, neither strain exhibited significant preference for the ALLOP
      solution versus water. However, the ALLOP-consuming B6 and D2 mice exhibited
      significant anxiolysis when they were tested on the elevated plus maze following
      8 days of ALLOP consumption, compared to separate animals that consumed only
      water. A subsequent study determined that systemic administration of PREG-HS had
      significant anxiolytic effects in both B6 and D2 mice, when assessed on the
      elevated plus maze. Plasma ALLOP levels in the steroid-consuming mice from both
      studies were significantly increased versus basal levels only in the D2 strain.
      While the pattern of steroid intake or strain differences in steroid conversion
      may have influenced the differential change in plasma ALLOP levels, it is
      noteworthy that both strains consumed doses of ALLOP, and presumably doses of
      PREG-HS, that were anxiolytic.

PMID- 14643845
TI  - Synergistic effects between codeine and diclofenac after local, spinal and
      systemic administration.
AB  - This study was designed to evaluate the extent of the antinociceptive interaction
      between codeine and diclofenac at the local, spinal and systemic level. The
      effects of individual and fixed-ratio combinations of locally, spinally or orally
      given codeine and diclofenac were assayed using the formalin test in rats.
      Isobolographic analysis was employed to characterize the synergism produced by
      the combinations. Codeine, diclofenac and fixed-ratio codeine-diclofenac
      combinations produced a dose-dependent antinociceptive effect when administered
      locally, spinally or systemically. ED(30) values were estimated for the
      individual drugs and isobolograms were constructed. Theoretical ED(30) values for
      the combination estimated from the isobolograms were 422.2+/-50.5 microg/paw,
      138.5+/-9.2 microg/rat, and 9.3+/-1.1 mg/kg for the local, spinal and oral
      routes, respectively. These values were significantly higher than the actually
      observed ED(30) values which were 211.1+/-13.6 microg/paw, 45.9+/-3.9 microg/rat,
      and 2.5+/-0.2 mg/kg, indicating a synergistic interaction. Systemic
      administration resulted in the highest increase in potency, being about fourfold,
      while spinal and local administration increased potency in two- and threefold,
      respectively. The fact that the highest synergism was observed after systemic
      administration suggests that the interaction is occurring at several anatomical
      sites. The results support the clinical use of this combination in pain
      management.

PMID- 14643846
TI  - Enhancement of learning processes following an acute modafinil injection in mice.
AB  - Modafinil is a wakeness-promoting drug, which is effective in the treatment of
      narcolepsy; its effects on learning processes are however little studied. Thus,
      the present study was aimed at determining the effects of an acute modafinil
      injection on a serial reversal discrimination task performed in a T-maze in mice.
      Independent groups of mice varying by the level of pretest training (either 1 or
      4 days of training) were used. Mice were injected each day with a gum arabic
      solution before each session began. On the second or the fifth day of training, a
      single dose of modafinil was injected before testing. Modafinil at 64 mg/kg but
      not at 32 mg/kg dramatically improved performance as compared to controls in
      subjects being trained 4 days, but not in subjects being trained 1 day. This
      improvement of learning was due to the more rapid emergence of a win-stay
      strategy in modafinil-treated subjects as compare to controls. Thus, our data
      show that an acute modafinil injection enhances learning processes.

PMID- 14643847
TI  - Environmental enrichment lowers stress-responsive hormones in singly housed male
      and female rats.
AB  - Structural and social aspects of an environmental system can influence the
      physiology and behavior of animals occupying that system. This study examined the
      physiological effects of environmental enrichment (EE) with Kong Toys and
      Nestlets on stress-responsive hormones of the hypothalamic-pituitary-adrenal
      (HPA) axis under basal and mild stress conditions in singly housed, jugular vein
      cannulated, male and female rats. Animals of both sexes housed with EE had
      significantly lower baseline adrenocorticotropic hormone (ACTH) and
      corticosterone (CORT) concentrations compared to those housed without EE. ACTH
      responses to the mild stress of saline injection were significantly lower in
      female rats housed with EE. Interaction with the Kong Toys and Nestlets appears
      to have provided the rats with a diversion from monotonous cage life, resulting
      in lower HPA axis activity before and after mild stress. These results are
      important because low, stable baselines are essential for accurately discerning
      pharmacological and other influences on the HPA axis.

PMID- 14643848
TI  - Effects of Ginkgo biloba on corticosterone stress responses after inescapable
      shock exposure in the rat.
AB  - Extracts from the leaves of the Ginkgo biloba tree (GBE) are found to be
      clinically effective in neuroprotection, cerebral and cardiovascular function and
      cognitive processing. Recent animal findings suggest that GBE also may improve
      stress adaptation and prevent learned helplessness, as evidenced by its reduction
      of behavioral acquisition deficits of active avoidance after inescapable shock
      exposure. In the present report, the effects of two doses of GBE were studied on
      corticosterone stress responses and acquisition of active avoidance after
      inescapable shock exposure. Forty-eight rats were divided into three groups:
      either receiving a daily dose of 50 mg/kg or 150 mg/kg of GBE (containing 24%
      flavonoid and 6% terpenoid) or vehicle for 2 weeks. After 2 weeks of
      administration, animals were trained for active-avoidance acquisition following
      inescapable shock exposure (stress induction) or nonshock exposure (nonstress).
      Administration of 150 mg/kg but not of 50 mg/kg of GBE significantly prevented a
      corticosterone stress response after inescapable shock exposure (P<.0001) without
      any beneficial behavioral effect on active avoidance. Repeated administration of
      GBE particularly improves biological adaptation to noxious stimuli without
      beneficial behavioral consequences. Present findings do not support previous
      claims about the benefits of G. biloba on improving behavioral stress adaptation
      and acquisition of active avoidance and on reducing behavioral deficits
      indicative of "learned helplessness."

PMID- 14643849
TI  - Repeated experience with naloxone facilitates acute morphine withdrawal:
      potential role for conditioning processes in acute opioid dependence.
AB  - Single injections with morphine can induce a state of acute opioid dependence in
      humans and animals, typically measured as precipitated withdrawal when an
      antagonist such as naloxone is administered 4-24 h after morphine. Repeated
      treatment with morphine at 24-h intervals can result in a progressive shift in
      potency of naloxone to produce such acute withdrawal signs, including suppression
      of operant responding for food reward. The current study characterized fully both
      morphine and naloxone dose-effect functions in an effort to establish the
      relative contributions of repeated morphine vs. repeated naloxone (Nal)
      experience to these potency shifts. Rats trained on an FR15 schedule for food
      received four vehicle or morphine injections (0.56-5.6 mg/kg sc), spaced 24 h
      apart. Four hours after each morphine pretreatment (Repeat Nal), or 4 h after the
      fourth and final morphine pretreatment only (Single Nal), a cumulative dose
      effect function for naloxone-induced suppression of responding was determined.
      Vehicle-pretreated (Morphine Naive) rats showed little change in the naloxone
      dose effect function even after four cumulative dose-effect determinations. By
      contrast, a progressive increase in naloxone potency was observed following
      successive pretreatments with morphine under Repeat Nal conditions, and the
      magnitude of naloxone potency shift was morphine dose dependent. At a morphine
      dose of 5.6 mg/kg, repeated naloxone experience in the presence of morphine was
      not an absolute requirement to produce an increase in naloxone potency across
      days, but repeated naloxone could potentiate the magnitude of the observed shift,
      indicating both experience-independent and experience-dependent processes at
      work. At lower doses of morphine (1.0 and 3.3 mg/kg) no shift in naloxone potency
      was observed across days of morphine treatment in the absence of repeated
      naloxone experience (Single Nal conditions), indicating an increasing
      contribution of naloxone experience-dependent processes as dose of morphine was
      decreased. It is argued that these experience-dependent processes in the
      progressive shift of naloxone potency observed in the current study may reflect
      an important role of conditioning in the early development of opioid dependence.

PMID- 14643850
TI  - Amphetamine modulation of paced mating behavior.
AB  - The present study evaluated the effects of acute and repeated, intermittent
      amphetamine administration on paced mating behavior in ovariectomized (OVX) rats
      primed with estrogen and progesterone. In Experiment 1, female rats were tested
      for paced mating behavior following acute administration of amphetamine (1.0
      mg/kg). Amphetamine increased the likelihood that a female would withdraw from a
      male following a mount or an intromission. Although this dose of amphetamine did
      not alter sexual receptivity or the latency to return to a male after sexual
      stimulation, locomotor activity was increased significantly. Experiment 2
      evaluated the dose response characteristics of acute amphetamine (0.5, 1.0 and
      2.0 mg/kg) administration on paced mating behavior. In agreement with Experiment
      1, amphetamine at all doses increased the likelihood that a female would withdraw
      from a male following sexual stimulation. In Experiment 3, female rats were
      tested for partner preference (sexually active male vs. estrous female) following
      acute amphetamine administration. Amphetamine treatment augmented both social and
      sexual preferences. In Experiment 4, female rats were administered estrogen (20
      microg/kg) and amphetamine (1.0 mg/kg) for 3 weeks and tested for paced mating
      behavior 1 and 4 weeks later, amphetamine free. Repeated intermittent exposure to
      amphetamine shortened the latency to return to a male after receiving a mount on
      the test conducted 1 week after the final drug injections. Collectively, these
      results suggest that the acute effects of amphetamine on paced mating behavior
      may reflect a reduction in social and sexual behaviors and an increase in
      locomotor activity, whereas the effects of repeated exposure may reflect a change
      in incentive motivation.

PMID- 14643851
TI  - 7-OH-DPAT selectively reduces intake of both chow and high fat diets in different
      food intake regimens.
AB  - Mesolimbic dopaminergic system activation correlates with ingestive behavior in
      numerous feeding regimens. DA release is enhanced by food intake following
      deprivation, amount of food consumed, and the palatability of the food consumed.
      The dopamine-3 receptor (D3-R) has a limited expression pattern that is
      restricted largely to the mesolimbic dopaminergic system. The D3-R has been
      hypothesized to inhibit DA-mediated reward, locomotion and motivation. To test
      the potential for an inhibitory role of the D3-R on food intake, we administered
      the D3-R agonist 7-OH-DPAT (5, 10 and 50 microg/kg ip) to rats that had ad
      libitum access to standard rodent chow (3.41 kcal/gm, 0.51 kcal/gm from fat) or a
      preferable, high fat (HF) (4.4 kcal/gm, 1.71 kcal/gm from fat). In the second set
      of experiments we administered 7-OH-DPAT (10, 50 and 100 microg/kg) to rats that
      had access to chow or HF diet for only 3 h per day (meal fed). In the third set
      of experiments we administered 7-OH-DPAT (10 and 50 microg/kg) to rats that had
      access to chow or HF diet after a 21-h food restriction. The 10 and 50 microg/kg
      doses significantly, but equally reduced intake of chow and HF diet in animals
      that were ad libitum fed. In animals that were meal-fed the dose response was
      effectively shifted to the right and the 10 microg/kg dose was ineffective at
      reducing intake. The 50 and 100 microg/kg doses significantly but equally reduced
      intake of both diets. In animals that were 21-h restricted and had access to chow
      both the 10 and 50 microg/kg doses were ineffective at reducing intake. However,
      in animals that had access to HF diet, 7-OH-DPAT dose-dependently reduced intake.
      These results support a potential role for the D3-R in ingestive behavior
      particularly in situations that involve a significant learned component.

PMID- 14643852
TI  - Hypericum perforatum extract demonstrates antioxidant properties against elevated
      rat brain oxidative status induced by amnestic dose of scopolamine.
AB  - This study was designed to investigate if the impairment of learning and memory
      induced by acute administration of scopolamine (1.4 mg/kg ip) in rats is
      associated with altered brain oxidative stress status. The passive avoidance
      paradigm was used to assess retrieval memory of rats after scopolamine treatment.
      Following retrieval testing, biochemical assessments of malondialdehyde (MDA),
      glutathione peroxidase (GSHPx), glutathione (GSH), and superoxide dismutase (SOD)
      levels/activities as oxidative stress indices were performed. This study also
      investigated the effect of acute administration of Hypericum perforatum extract
      (4.0, 8.0, 12.0, and 25.0 mg/kg ip), containing flavonoids with documented
      antioxidant activity, on brain oxidative status of nai;ve rats treated with
      amnestic dose of scopolamine. Results showed that administration of 1.4 mg/kg of
      scopolamine impaired retrieval memory of rats and that such amnesia was
      associated with elevated MDA and reduced GSH brain levels. In nai;ve rats, which
      have not been exposed to conditioned fear, scopolamine administration also
      increased MDA and reduced GSH levels, although with an increase in brain GSHPx
      activity. Pretreatment of the animals with Hypericum extract (4, 8, and 12 mg/kg)
      resulted in an antioxidant effect through altering brain MDA, GSHPx, and/or GSH
      level/activity. Since oxidative stress is implicated in the pathophysiology of
      dementia, the findings of this study may substantiate the value of scopolamine
      induced amnesia in rats as a valid animal model to screen for drugs with
      potential therapeutic benefit in dementia. Exposure of animals to conditioned
      fear may be suggested to impair the balance between the rate of lipid
      peroxidation and the activation of GSHPx as a compensatory antioxidant protective
      mechanism. It is also concluded that low doses of Hypericum extract,
      demonstrating antioxidant activity, may be of value for demented patients
      exhibiting elevated brain oxidative status. Since depression commonly coexists
      with dementia, Hypericum extract as a drug with documented antidepressant action
      may also be a better alternative than several other antidepressant medications
      that have not been evaluated to test their effect on brain oxidative status
      during amnesia.

PMID- 14643853
TI  - Oestrogen receptor-beta and neurohypophysial hormones: functional interaction and
      neuroanatomical localisation.
AB  - Oestrogens affect fluid balance, influencing both ingestive behaviour and renal
      excretion. The renal effects are partly due to altered release of vasopressin and
      oxytocin. This study was designed to explore the role of oestrogen receptor-beta
      (ERbeta) in neurohypophysial hormonal function. Following dietary administration,
      soya isoflavones reach the brain in sufficient concentration to activate ERbeta,
      but not oestrogen receptor-alpha (ERalpha). ERbeta function was therefore
      manipulated by feeding rat diets differing in soya isoflavone content. Fluid
      balance and neurohypophysial hormone release were measured in male rats
      maintained for 14 days on a soya isoflavone-free diet or one containing 150
      microg/g genistein+daidzein. Food and water intake, body weight, urine flow,
      osmolality and sodium concentrations were determined daily. After 14 days, plasma
      and urine osmolality and sodium, vasopressin and oxytocin concentrations were
      determined. There was no significant difference in weight gain between the two
      groups or in their excretion of sodium and water or plasma sodium and plasma
      oxytocin. However, plasma vasopressin was significantly lower in the iso-free
      group. Double-label immunocytochemistry was used to assess colocalisation of
      ERbeta with the neurohypophysial hormones in male rats. Cell nuclei showing
      ERbeta immunoreactivity were abundant in the posterior magnocellular
      paraventricular nucleus (PVNpm) and in the supraoptic nucleus (SON). Vasopressin
      immunoreactive neurones were similarly distributed, forming the core of the PVNpm
      and the ventral portion of the SON; majority were positive for ERbeta. Cells with
      oxytocin immunoreactivity were located mainly at the periphery of the PVNpm and
      in the dorsal SON; only approximately a quarter of these cells showed ERbeta
      immunoreactivity. Thus, the difference in the effects of the soya diet on
      vasopressin and oxytocin release may be related to the ERbeta-activating
      properties of this diet and to the preponderance of this receptor in vasopressin
      as opposed to oxytocin cells.

PMID- 14643854
TI  - Acquisition of lever pressing for cocaine in C57BL/6J mice: effects of prior
      Pavlovian conditioning.
AB  - The purpose of this study was to determine (1) if C57BL/6J (C57) mice would lever
      press for intravenous cocaine infusions in a limited-access paradigm without
      previously establishing the instrumental response with natural reinforcers and
      (2) if prior Pavlovian conditioning of cocaine to the response contingent
      stimulus complex used in the cocaine self-administration sessions would
      facilitate acquisition of lever responding for cocaine. After implanting jugular
      catheters, some mice received Pavlovian conditioning during which 12 passive
      cocaine infusions (0.1 or 1 mg/kg unit doses) were paired with the
      tone/light/pump sound stimulus complex used in the self-administration sessions.
      The remaining mice simply began the cocaine self-administration sessions for 0.1
      or 1 mg/kg unit doses of cocaine. Twenty-seven of the 33 mice with patent
      catheters acquired stable lever responding within an average of 5 to 6 days
      without previously establishing the instrumental response with natural rewards.
      Prior Pavlovian pairing of cocaine with the response contingent stimulus complex
      used in the self-administration sessions did not influence the acquisition of
      cocaine self-administration at the highest cocaine dose (1 mg/kg). This
      conditioning procedure using the low cocaine dose (0.1 mg/kg/infusion) reduced
      the number of mice acquiring cocaine self-administration to 50%, and the number
      of mice developing stable response patterns was only 25%. The results establish
      that C57 mice can acquire cocaine self-administration over several unit doses in
      a limited-access paradigm without previously establishing the instrumental
      response with natural reinforcers. Furthermore, prior pairing of response
      contingent cues with cocaine via Pavlovian conditioning did not facilitate the
      acquisition of cocaine self-administration.

PMID- 14643855
TI  - Behavioral effects of dopamine agonists and antagonists in MPTP-lesioned D3
      receptor knockout mice.
AB  - To test the modulatory role of D(3) receptors in normal and dopamine-depleted
      mice, D(3) receptor KO mice and wild-type (WT) littermates were administered
      saline, L-dopa/carbidopa (20/2 mg/kg ip), a preferential D(3)>D(2) agonist
      S32504, a D1+D(2)/D(3) agonist apomorphine, a selective D(3) antagonist S33084,
      or apomorphine with S33084 prior to and after administration of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). We monitored lines crossed in a 55-min
      session, average number of rears, and average number of grooming bouts. MPTP
      treatment produced equivalent 70% losses of dopamine fibers in the caudate
      putamen (CPu) and nucleus accumbens (NAC) of WT and D(3) KO mice as compared to
      their control (vehicle injected) counterparts. D(3) receptors were absent in KO
      mice, and the number of D(3) receptors was unaffected by MPTP-induced loss of DA
      terminals in WT mice. The results support a lack of involvement of the D(3)
      receptor for D1:D2 receptor-mediated behavioral activity (synergy). First, S32504
      inhibited all behaviors and to a similar degree in D(3) KO and WT mice. Second,
      S33084 at the higher concentration increased number of lines crossed in response
      to high dose apomorphine in both D(3) KO and WT mice. Third, in nonlesioned mice,
      apomorphine-induced gnawing stereotypies were inhibited by S33084 in both D(3) KO
      and WT mice. Interestingly, the inhibition of apomorphine-induced gnawing was not
      apparent in MPTP-lesioned mice, and this stereotypy was elevated in D(3) KO-MPTP
      lesioned mice. Thus, the suppressive effects of S32504 could be via D2
      autoreceptor inhibition of DA release, and D2 receptor blockade by S33084 leads
      to release of that inhibition. This may be more apparent in MPTP-lesioned
      partially DA denervated mice.

PMID- 14643856
TI  - Activation of GABAA and opioid receptors reduce penile erection induced by
      hexarelin peptides.
AB  - The effect of muscimol, a GABA(A) receptor agonist, and of morphine, an opioid
      receptor agonist, on penile erection induced by the hexarelin analogue peptide EP
      80661 (GAB-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2)) and on the increase in the
      concentration of NO(2)(-) and NO(3)(-) that occurs concomitantly in the dialysate
      obtained from the paraventricular nucleus (PVN) of the hypothalamus by
      intracerebral microdialysis, was studied in male rats. Muscimol (50, 100 and 200
      ng) and morphine (0.1, 0.5, 1 and 5 microg) given into the PVN dose-dependently
      reduced penile erection induced by EP 80661 (1 microg) injected into the PVN. The
      reduction of penile erection was parallel to a decrease of the concomitant NO(2)(
      ) and NO(3)(-) increase that occurs in the paraventricular dialysate in these
      experimental conditions. Muscimol and morphine effects on EP 80661-induced penile
      erection and NO(2)(-) increase were prevented by the prior administration into
      the PVN of bicuculline (250 ng) and naloxone (5 microg), respectively. The
      present results show that the activation of GABA(A) receptors and of opioid
      receptors in the PVN reduces penile erection induced by hexarelin analogue
      peptides by reducing the increase in NO activity that occurs in this hypothalamic
      nucleus in these experimental conditions.

PMID- 14643858
TI  - Vitrification of bovine oocytes and its application to intergeneric somatic cell
      nucleus transfer.
AB  - We determined the efficacy of a microdrop vitrification procedure for
      cryopreservation of bovine oocytes, using vitrified oocytes as cytoplasts for
      intraspecies and intergeneric somatic cell nucleus transfer (NT). In vitro
      matured bovine MII oocytes were vitrified in microdrops with a vitrification
      solution containing 35% ethylene glycol, 5% polyvinyl pyrrolidone, and 0.4 M
      trehalose. After warming, approximately 80% of the vitrified oocytes were
      morphologically normal, and their enucleation rate was similar to that of fresh
      oocytes. The NT embryos constructed with bovine cumulus cells and the vitrified
      oocytes developed similar to blastocysts constructed with fresh oocytes, although
      the cell number of NT blastocysts originating from vitrified oocytes was lower
      than that of the fresh control. In a second experiment, we examined the
      development of NT embryos constructed with vitrified bovine oocytes and bovine
      fibroblasts (intraspecies NT embryos) or swamp buffalo fibroblasts (intergeneric
      NT embryos). There were no differences between the intraspecies and intergeneric
      NT embryos in fusion, cleavage and development to blastocysts, except for lower
      cell numbers in the intergeneric NT blastocysts. In conclusion, the efficacy of
      this microdrop vitrification procedure and the production of swamp buffalo NT
      blastocysts using vitrified bovine oocytes was demonstrated.

PMID- 14643857
TI  - Impact of changes in composition of storage medium on lipid content and quality
      of turkey spermatozoa.
AB  - Turkey semen quality is damaged by long term in vitro storage. The objective of
      the present study was to determine whether changes in energy substrates and
      antioxidants of semen extender could limit loss of quality and lipid content of
      turkey spermatozoa during storage. Spermatozoa were incubated in extenders based
      on Beltsville Poultry Semen Extender (BPSE) to which different energy substrates
      (acetate, pyruvate and hydroxybutyric acid) or antioxidant (Vitamin E) had been
      added. Semen was stored at 4 degrees C for 48 h and changes in quality,
      phospholipid and malondialdehyde (MDA) content of semen were evaluated. Among the
      different substrates studied, only acetate was able to limit the loss of motility
      and ATP content after 48 h in vitro storage. Losses of spermatozoal phospholipids
      were similar when gametes were incubated in an extender without any substrate or
      in normal BPSE (784-675nmol/10(9) spz versus 837-703 nmol/10(9) spz). However,
      motility and ATP content were significantly more affected after 48 h of storage
      in samples incubated without substrates than in BPSE (motility, 2.2 versus 0;
      ATP, 10 nmol/10(9) spz versus 3 nmol/10(9) spz). The addition of Vitamin E to the
      extender did not modify either the MDA or phospholipid content of fresh or stored
      spermatozoa, but increased the motility of stored semen. In conclusion, acetate
      is an essential substrate for in vitro storage. Spermatozoal phospholipids
      decreased during storage, but this did not seem to originate from metabolism of
      endogenous fatty acids. The positive effects of Vitamin E on semen storage did
      not originate from preservation of lipid oxidation.

PMID- 14643859
TI  - Effect of whole blood and serum on bovine sperm quality and in vitro
      fertilization capacity.
AB  - Under physiologic conditions, low concentrations of blood may be present in the
      uterine fluid of the estrous cow at the moment of insemination. To decrease the
      insemination dose and to obtain good insemination results with less fertile
      semen, more invasive insemination methods such as utero tubal junction (UTJ)
      insemination can be used. More invasive insemination methods increase the risk of
      damaging the hyperemic endometrium, with blood in the uterine fluid as result. In
      this study, the effect of 0, 0.15 and 1.5% whole blood and serum on bovine sperm
      quality and in vitro fertilizing capacity was evaluated. Sperm quality as
      assessed by total motility, progressive motility, membrane integrity and
      acrosomal status was not affected by the presence of blood or serum (P > 0.05).
      However, the in vitro fertilizing capacity decreased with increasing
      concentrations of blood and serum (P < 0.01). The rate of polyspermy increased
      with increasing concentrations of serum (P < 0.01), but not with increasing
      concentrations of blood (P = 0.30). In conclusion, no immediate effect of blood
      and serum was visible on several sperm quality parameters, except for an
      increased prevalence of head to head agglutination (HHA). However, blood and
      serum did have a negative effect on in vitro fertilizing capacity.

PMID- 14643860
TI  - Role of potassium channels, the sodium-potassium pump and the cytoskeleton in the
      control of dog sperm volume.
AB  - Response to osmotic shock is an important aspect of mammalian sperm physiology.
      In this study we recorded volume changes of dog spermatozoa at 39, 33, and 25
      degrees C under isotonic conditions and following hypotonic shock. Cell volume
      measurements were performed electronically in saline solutions of 300 and 150
      mOsmol kg(-1), and Percoll-washed preparations were compared with unwashed
      samples. The involvement of potassium channels in volume control was tested by
      treatment with quinine, while the involvement of the plasma membrane Na(+)-K+
      pump was tested by treatment with ouabain. The role of the cytoskeleton was
      investigated by treatment with colchicine and cytochalasin D. The number of cell
      populations observed varied with temperature and tonicity. In both types of sperm
      preparations, between two and three populations were present under isotonic
      conditions at 25 degrees C whereas at 39 and 33 degrees C only one population was
      detected. Hypotonic stress at the higher temperatures caused the single
      population to swell, whereas at 25 degrees C it resulted in a population of cells
      whose modal volume was similar to that of the middle isotonic sub-population.
      Both quinine and the cytoskeletal inhibitors markedly increased swelling both
      under hypotonic conditions at 39 degrees C and under isotonic conditions at 25
      degrees C. However, little or no effect of ouabain was observed. We conclude that
      in dog spermatozoa swelling in response to hypotonic conditions is minimised
      through the activity of potassium channels and the presence of an intact
      cytoskeletal network. Under isotonic conditions at 25 degrees C, a considerable
      proportion of the sperm population is already swollen; this swelling varies
      between individual males and appears to be due to lowered cytoskeletal and
      potassium channel activity.

PMID- 14643861
TI  - Effects of Trypanosoma vivax and Trypanosoma congolense infections on the
      reaction time and semen characteristics of Zebu (Bunaji) x Friesian crossbred
      bulls.
AB  - The effect of trypanosomosis on reaction time and semen characteristics of 12
      Zebu (Bunaji) x Friesian crossbred bulls aged between 3 and 5 years was studied
      for a duration of 12 weeks. Four of the bulls were infected with Trypanosoma
      vivax, another four with Trypanosoma congolense and the remaining four bulls
      served as controls. Rectal temperatures and haematological parameters were
      monitored twice weekly. The pre-infection mean value of the rectal temperature
      was 38.3 degrees C, and this rose to a mean of between 40.5 and 41.1 degrees C in
      the infected animals. Concurrently, the infected animals exhibited signs of
      anaemia shown by pale mucous membranes and decreased packed cell volume (PCV),
      weight loss, lethargy, weakness and dullness. The reaction time (ejaculation
      time) of semen collection significantly increased from a pre-infection mean value
      of 20.46-25.14 s to a mean of 290.33-301.15 s within 12 weeks post-infection.
      Semen characteristics deteriorated progressively within the same period in the
      infected bulls. There were highly significant and drastic decreases in sperm
      concentration and volume of semen and increases in sperm morphological defects.
      By the third week, all the infected bulls were unfit for breeding because of very
      poor semen characteristics. Deterioration, also characterized by oligospermia at
      6 weeks post-infection in all bulls which later culminated in azoospermia in two
      bulls infected with T. vivax and two bulls infected with T. congolense continued
      to the end of the investigation. The present results indicate that trypanosomosis
      due to T. vivax and T. congolense infections is very pathogenic and devastating
      in its effect on the reaction time (ejaculation time) and semen characteristics
      which resulted in very poor semen quality. The practical implication is
      infertility and sterility in Zebu x Friesian crossbred bulls in trypanosome
      endemic areas.

PMID- 14643862
TI  - Effect of hyaluronan supplementation on boar sperm motility and membrane lipid
      architecture status after cryopreservation.
AB  - We investigated the effect of supplementing extended boar semen with different
      amounts of hyaluronan (HA) prior to freezing on post-thaw sperm characteristics.
      Using a split sample design, the effect of HA at a final concentration of 500 or
      1000 microg/ml semen on post-thaw motility parameters, and membrane lipid
      architecture status assessed by merocyanine-540/YOPRO-1 and flow cytometry were
      evaluated. HA-supplementation improved motility parameters (P < 0.05 to P <
      0.001) and decreased the percentage of hyperactivated spermatozoa (P < 0.05). HA
      supplemented samples had more spermatozoa showing high lipid membrane stability
      as assessed with merocyanine-540. In conclusion, HA appeared to preserve post
      thaw spermatozoa viability in vitro and maintained membrane stability after
      cryopreservation.

PMID- 14643863
TI  - Addition of beta-mercaptoethanol or Trolox at the morula/blastocyst stage
      improves the quality of bovine blastocysts and prevents induction of apoptosis
      and degeneration by prooxidant agents.
AB  - This study was conducted to evaluate the effect of beta-mercaptoethanol (a
      stimulator of glutathione synthesis) and Trolox (an hydrosoluble analogue of
      Vitamin E) on bovine embryos cultured from the morula stage (Day 5 post
      insemination; pi) under oxidative stress conditions. Culture of embryos with
      increased doses of Trolox showed a dose-dependent embryotoxicity on Day 8 pi. The
      use of 400 microM Trolox as well as beta-mercaptoethanol at 100 microM prevented
      at least partly (P < 0.05) the prooxidant-induced blastocyst degeneration on Day
      8. Hatching rates of surviving blastocysts were significantly increased by both
      antioxidants and beta-mercaptoethanol alone improved their mean cell numbers,
      which was significant in the ICM (P < 0.05). Analysis of their effect on Day 7 pi
      showed that both the antioxidants significantly reduced the prooxidant-induced
      apoptosis and beta-mercaptoethanol diminished the physiological level of
      apoptosis as well as it stimulated the glutathione synthesis (P < 0.05). In
      addition, a comparison between in vitro- and in vivo-produced embryos showed that
      the levels of apoptosis were similar at the same age post-insemination (morulae
      and blastocysts) but increased steadily with the embryonic age in in vitro ones.
      In conclusion, beta-mercaptoethanol and Trolox added separately from the morula
      stage protected embryos against oxidative stress and improved the quality of the
      resulting blastocysts.

PMID- 14643864
TI  - Susceptibility of pig embryos to porcine circovirus type 2 infection.
AB  - The aim of the present study was to determine if porcine circovirus type 2 (PCV2)
      is able to infect embryonic cells of in vivo produced porcine embryos with and
      without zona pellucida (ZP). ZP-intact and ZP-free morulae (6-day post
      insemination) and early blastocysts (7-day post-insemination), and hatched
      blastocysts (8-day post-insemination) were exposed to 10(5.0) TCID50 PCV2 per ml
      (strain 1121, fifth passage PK15). At 48 h post-incubation, the percentage of
      infected embryos and the percentage of viral antigen-positive cells per embryo
      were determined by indirect immunofluorescence (IF). Significantly different
      percentages of infected embryos were detected: 15% for ZP-free morulae, 50% for
      ZP-free early blastocysts and 100% for hatched blastocysts. The percentage of
      cells that expressed viral antigens was similar for the three stages of
      development. PCV2 exposure did not affect the in vitro development of the embryos
      during the 48 h study period. All ZP-intact embryos remained negative for viral
      antigens. In an additional experiment the diameter of the channels in the porcine
      ZP was determined. After incubation of early blastocysts with fluorescent
      microspheres of three different sizes, beads with a diameter of 20 nm and beads
      with a diameter of 26 nm crossed the zona whereas beads with a diameter of 200 nm
      did not. In conclusion, it can be stated that PCV2 is able to replicate in in
      vivo produced ZP-free morulae and blastocysts and that the susceptibility
      increases during development. The ZP forms a barrier to PCV2 infection, but based
      on the size of the channels in the ZP the possibility that PCV2 particles cross
      the ZP cannot be excluded.

PMID- 14643865
TI  - Assessment of a new utero-tubal junction insemination device in dairy cattle.
AB  - A new artificial insemination device for semen deposition near the utero-tubal
      junction in cattle (Ghent device) has been developed at the Ghent University
      (Belgium). In this study, the effect of the new insemination device on sperm
      quality was evaluated. Moreover, in a field trial 4064 dairy cows were
      inseminated by 12 inseminators to examine the efficacy of the device under field
      conditions. The Ghent device is a disposable plastic catheter which can easily
      follow the curvature of the uterine horns and thus reach the utero-tubal junction
      (UTJ). After expulsion of the inseminate with 0.7 or 1.7 ml of air, 19.0% of the
      insemination dose remained in the insemination catheter. Sperm loss can be
      diminished to 9.0% of the original insemination dose when the insemination
      catheter is flushed with 0.1 ml of air, followed by 0.6 ml of physiological
      saline solution. No toxic effect of the insemination catheter on sperm quality or
      fertilizing capacity was found. In the field trial, sperm were inseminated in
      dairy cattle which were divided in three groups. The first group was inseminated
      in the uterine body with the conventional insemination device, the second group
      in the uterine body with the Ghent device, and the third group in the tip of both
      uterine horns with the Ghent device. Each insemination was performed with 10 x
      10(6) to 15 x 10(6) frozen-thawed spermatozoa. The pregnancy rates (PRs) were
      significantly affected by the insemination technique (P = 0.02), by the
      inseminator (P = 0.01), by heifer or cow (P < 0.01), and by the insemination
      number (P < 0.01). Pregnancy rates obtained with the conventional insemination
      device (57.6%) were significantly better than those obtained with the Ghent
      device in the uterine body (52.7%) (P < 0.01), but did not differ significantly
      from those obtained after deep insemination into both uterine horns (53.8%) (P =
      0.27). It can be concluded that the Ghent device is suitable for utero-tubal
      junction insemination of dairy cattle under field conditions. Whether the Ghent
      device is also suitable for insemination with lower insemination doses is at
      present under investigation.

PMID- 14643866
TI  - Large scale assessment of the effect associated with bovine viral diarrhoea virus
      infection on fertility of dairy cows in 6149 dairy herds in Brittany (Western
      France).
AB  - This study aimed at quantifying on a large scale the risk of both three-week
      return-to-service and late-return-to-service for dairy cows according to the BVDV
      infection status of the herds. Three-week- and late-returns-to-service were
      defined as a repeat service occurring respectively from 19 to 25 days and after
      25 days following a first or a second service. The level of BVDV-specific
      antibodies in bulk tank milk were measured four times at four months intervals by
      a blocking ELISA test to define five BVDV-infection-herd-statuses: (i) presumed
      non-infected herds for a long time, (ii) presumed not-recently-infected herds,
      (iii) presumed past-infected-recently-recovered herds, (iv) presumed past
      steadily-infected herds, (v) presumed recently-infected herds. A total of 150,854
      AIs from 122,697 cows in 6149 herds was included in the analysis. The risk of
      return-to-service was assessed using logistic regression and survival analysis
      models. The BVDV-infection-herd-status was not significantly associated with the
      risk of 3-week-return-to-service, but significantly with that of late-return-to
      service. Cows in herds presumed past-infected-recently-recovered, past-steadily
      infected, or recently-infected had a significantly higher risk of late-return-to
      service (relative risk of 1.03, 1.11, 1.12, respectively) compared with cows in
      herds presumed not-recently-infected. Risk of late-return-to-service was not
      significantly different in cows from herds presumed non-infected for a long time
      or not-recently-infected. In conclusion, BVDV-infection was found to mainly
      increase the risk of embryonic and foetal death.

PMID- 14643867
TI  - Effects of retention of fetal membranes on subsequent reproductive performance of
      dairy ewes.
AB  - Seventy-one pairs of ewes with or without retention of fetal membranes in the
      previous lambing season, were included in a cohort study of 25 flocks in southern
      Greece; in 27 pairs regulation of the breeding cycle was applied, whilst in the
      other 44 pairs natural mating took place. The following measures of reproductive
      performance were calculated: cycling rate, mating rate, return-to-estrus rate,
      abortion rate, lambing rate, total lambs born per ewe, liveborn lambs per ewe,
      stillbirth rate, lamb-bodyweight per ewe; furthermore, the incidence risk of
      retention of fetal membranes during the lambing examined in this study was also
      calculated. No statistically significant differences were observed in the
      reproductive performance among ewes that had or had not retained their fetal
      membranes during the previous lambing, whether the breeding cycle was regulated
      or not. The incidence risk of retention of fetal membranes among ewes that had
      not retained its placenta in the previous lambing was 1.6%, whilst that among
      ewes that had retained its placenta in the previous lactation was 0%. It is
      concluded that retention of fetal membranes did not appear to adversely affect
      subsequent reproductive performance of ewes.

PMID- 14643868
TI  - Successful nonsurgical deep uterine embryo transfer in pigs.
AB  - At present, it is possible to transfer pig embryos directly into the uterine body
      of sows by nonsurgical procedures. The aim of this study was to develop a
      procedure for nonsurgical embryo transfer (ET) into the upper part of one uterine
      horn in gilts and sows. In experiment 1, 29 gilts and 43 sows were used.
      Intrauterine insertions took place for each female at days 4-6 of the estrous
      cycle (D0 = onset of estrus). An artificial insemination (AI) spirette was
      inserted into the cervix to assist with the guidance of a modified flexible
      catheter originally developed for deep intrauterine insemination in pigs. The
      flexible catheter length inserted anterior to the inserted AI spirette was 43.0
      +/- 1.7 cm. The time required to complete the procedure was affected by the type
      of female (P < 0.001) and by the difficulties encountered for inserting the
      catheter (P < 0.001). However, when no or minor difficulties were encountered
      during the insertion of the catheter (in approximately 70 and 80% of gilts and
      sows, respectively), the time required to complete the procedure did not differ
      between gilts (2.5 +/- 0.1 min) and sows (2.3 +/- 0.1 min). In experiment 2, 24
      to 31 fresh morulae and/or blastocysts were transferred to each of 24 recipients.
      Seventeen animals (70.8%) farrowed an average of 6.9 +/- 0.7 piglets, of which
      0.6 +/- 0.3 piglets were born dead. In conclusion, the procedure described in
      this study offers new possibilities to transfer embryos nonsurgically to the
      uterine horn of pigs.

PMID- 14643869
TI  - Development, DNA fragmentation and cell death in porcine embryos after 24 h
      storage under different conditions.
AB  - For practical applications of porcine embryo transfer (ET) it is important to
      develop feasible embryo storage conditions. The aim of the present study was to
      evaluate the effect of short-term storage (24 h) on the quality of in vivo
      produced porcine embryos. Three temperatures 18, 25 and 38 degrees C and three
      different media: Dulbecco's phosphate buffered saline (DPBS), TCM199 and Emcare,
      were tested for two different embryo ages: D4 embryos (collected 144 h after hCG
      treatment) and D5 embryos (collected 168 h after hCG). After slaughter of the
      donor gilts, embryos were collected and transported at 25 degrees C to the lab
      where morulas and blastocyst were selected (D4 n = 222; D5 n = 167) and randomly
      used as controls or distributed over the treatment groups. Developmental stage
      and embryo diameter were assessed by normal light microscopy, while total number
      of cells and incidence of apoptosis were assessed using a fluorescent embryo
      quality staining technique that combines three different dyes: Ethidium Homodimer
      (EthD-1), TUNEL and Hoechst 33342. Following 24 h storage, D5 embryos had higher
      rates of hatching (24%) and degeneration (9%) compared to D4 embryos (10 and 4%,
      respectively; P < 0.05). Embryos stored at 38 degrees C had higher rates of
      hatching (37%) compared to those ones stored at 25 degrees C (13%) or 18 degrees
      C (0%; P < 0.01). More embryos hatched when stored in medium Dulbecco's phosphate
      buffered saline (DPBS) or in TCM199 compared to those stored in Emcare (P <
      0.05). A higher percentage of embryos stored at 18 degrees C degenerated compared
      to those stored at 25 or 38 degrees C (P < 0.01). No significant increase in
      apoptosis was observed after storage compared to the rates of apoptosis at 0 h
      (controls) or between the different storage groups. Based on the results we
      conclude that D4 porcine embryos produced in vivo, selected under normal light
      microscopy and stored at 25 degrees C in a serum free medium for 24 h will have a
      suitable developmental stage for ET and a high embryo quality.

PMID- 14643870
TI  - Influence of exogenous GnRH on sexual behavior and frozen/thawed semen viability
      in stallions during the non-breeding season.
AB  - Twelve fertile stallions were divided into two groups, either receiving
      gonadotropin-releasing hormone (GnRH) (n = 6) or Placebo (n = 6). Based on the
      history of frozen/thawed semen characteristics three stallions within each group
      were assigned as being "good freezers" [GnRH (+); Placebo (+)] and three
      stallions were assigned as being "poor freezers" [GnRH (-); Placebo (-)]. The
      study was performed as a "blinded" investigation and stallions were treated twice
      daily by an intramuscular injection of 1 ml GnRH (Buserelin), 50 microg) or
      Placebo. The experiment was divided into three time periods. Period A (pre
      treatment) was performed between 16 November and 20 December; Period B
      (treatment) was performed during 6 weeks between 21 December and 31 January; and
      Period C (post-treatment) was performed between 1 February and 12 February. Semen
      was collected every Monday, Wednesday, Friday, and analysed for motion
      characteristics by the use of a computerized semen analyser, and sperm morphology
      immediately after collection. The spermatozoa were cryopreserved, stored in
      liquid nitrogen, and evaluated for motility (computer assisted semen analysis),
      membrane integrity (carboxyfluoresceine diacetate (CFDA) combined with propidium
      iodide (PI), CFDA/PI), viability and sperm morphology (Eosine-Nigrosine, EN), and
      osmotic reactivity (hypo-osmotic swelling test, HOS) following thawing in a water
      bath. The viability of spermatozoa was expressed as the difference between pre
      freeze and post-thaw values. A libido score of 1-4, the number of mounts on the
      phantom before ejaculation, and ejaculation latency were used to evaluate the
      stallions sexual behavior. Effect of treatment was analysed by comparing time
      intervals within groups as well as comparing groups within time intervals using
      SAS statistics software. GnRH treatment decreased the number of mounts before
      ejaculation (GnRH (total): 2.5 +/- 1.14 versus 1.8 +/- 1.06, P < 0.05), and
      shortened ejaculation latency. Cessation of treatment increased ejaculation
      latency in the GnRH group (4.7 +/- 4.98 min versus 7.2+/-7.88min, P<0.05). With
      the exception of libido score all parameters of sexual behavior were superior in
      the GnRH (+) group compared to the Placebo (-) group during the treatment period
      (P < 0.05). GnRH administration increased progressive motility (GnRH (+): 30.7 +/
      10.74% versus 38.4 +/- 15.1%, P < 0.05; GnRH (total): 24.9 +/- 11.80% versus
      31.9 +/- 14.68%, P < 0.05), membrane intact spermatozoa CFDA/PI (GnRH (-): 16.8
      +/- 7.17% versus 26.2 +/- 7.02%, P < 0.05; GnRH (total): 23.1 +/- 12.33% versus
      29.5 +/- 10.77%, P < 0.05) and HOS positive spermatozoa (GnRH (+): 33.2 +/-
      11.29% versus 42.2 +/- 10.36%, P < 0.05; GnRH (total): 32.9 +/- 10.23% versus
      40.1 +/- 10.30%, P < 0.05) of frozen/thawed spermatozoa. Following cessation of
      treatment, the viability of frozen/thawed spermatozoa decreased. GnRH treated
      stallions had lower losses of live stained spermatozoa (EN) compared to the
      Placebo group (GnRH (total): 17.6 +/- 4.77 versus Placebo (total): 27.2 +/- 5.44,
      P < 0.05). This was particularly observed in the "poor freezer" group (GnRH (-):
      16.6 +/- 4.35 versus Placebo (-): 31.3 +/- 5.87; P < 0.05). In conclusion,
      exogenous GnRH was shown to improve sexual behavior and increase the quality of
      frozen/thawed spermatozoa in fertile stallions during the non-breeding season.
      Nevertheless, it seems that, although significance was achieved relative to
      improvement to post-thaw sperm quality, that the "real" change in sperm quality
      seems negligible in fertile stallions. The mechanism of GnRH effect was not
      determined but this study may support the possibility of a direct gonadal or
      epididymal effect of exogenous GnRH in the stallion.

PMID- 14643871
TI  - Boar spermatozoa encapsulated in barium alginate membranes: a microdensitometric
      evaluation of some enzymatic activities during storage at 18 degrees C.
AB  - The customary dilution of boar semen for subsequent artificial insemination (AI)
      procedures damages the cell membrane of spermatozoa, resulting in a loss of
      enzymes and other cytoplasmic contents and acrosomal reactions. We encapsulated
      non-diluted boar semen in barium alginate membranes to optimize AI procedures and
      to improve the functional integrity of spermatozoal membranes during storage. The
      percentage of non-reacted acrosomes (NRA) and measurements of enzyme leakage
      (cytochrome c oxidase (COX), lactate dehydrogenase (LDH), and glucose-6-phosphate
      dehydrogenase (G6PDH)) were used as indices of the functional status of diluted,
      unencapsulated and encapsulated spermatozoa, stored for 72 h at 18 degrees C.
      Enzymatic activity was assessed in situ by microdensitometry, and non-reacted
      acrosomes were microscopically determined by staining. The percentage of acrosome
      integrity and the intracellular enzymatic activities during storage were
      different for unencapsulated and encapsulated semen. Semen dilution caused a
      rapid decline in enzymatic activities and concomitant acrosomal reactions.
      Encapsulated spermatozoa had significantly higher acrosome integrity (77% versus
      55%; P < 0.01 after 72 h) and an overall higher in situ enzymatic activity. For
      cytochrome c oxidase and lactate dehydrogenase the greatest differences between
      encapsulated and unencapsulated spermatozoa were present after 72 h whereas for
      glucose-6-phosphate dehydrogenase significant differences were found within 24h
      of storage. The encapsulation process maintains a better preservation environment
      for boar spermatozoa and could be a promising, innovative technique to improve
      storage of these cells.

PMID- 14643872
TI  - The effect of modified eros centre, outdoor raising or conventional group housing
      on breeding gilts and its effects on reproductive performance over four parities.
AB  - The present study was conducted in a large Croatian "built up unit". The
      objective of the study was to determine if an indoor modified eros centre (MEC)
      compared to indoor or outdoor group housing of gilts, influenced the onset of
      puberty of gilts and the reproductive performance of the evaluated females (n =
      783) over four parities. The gilts were from the same nucleus herd. Gilts of same
      age (140-150 days of age), body condition (body condition score of 3-4) and
      similar genetics (four-way cross females), during the same season (January to
      April 1999), were randomly divided at arrival into three groups and treated as
      follows:MEC gilts (n = 279): These were placed into indoor MEC pens in groups of
      8-10. The gilts had continuous fenceline contact to boars (one boar to two groups
      of gilts, boars were changed daily) and to shortly weaned oestrous sows. Gilts
      were regrouped and dislocated at 10-day intervals. Outdoor gilts (n = 263): These
      were kept in groups of 8-10 on a large pasture (80-100 m2 per group). The animals
      had fenceline contact to mature boar for 5-10 min daily. Control indoor gilts (n
      = 241): These were housed indoors in large pens in groups of 8-10. The animals
      had fenceline contact to mature boars for 5-10 min daily. Each outdoor group had
      an insulated hut with straw bedding. All gilts were fed ad libitum with the same
      commercial diet. Housing gilts in MEC resulted in earlier (P < 0.001) onset of
      estrus (MEC: 174.8 +/- 2.4 days, indoor group housing: 207.6 +/- 4.1 days,
      outdoor group housing: 187.4 +/- 2.1 days) and lower (P < 0.001) farrowing rate
      to first service (MEC: 70.97%, indoor group housing: 89.73%, outdoor group
      housing: 89.62%). Farrowing rate of regularly returning MEC gilts to second
      service was 95.00%. First total-born litter size, first liveborn litter size,
      first wean-to-estrus interval (WEI), percent of sows bred after first weaning,
      second total-born litter size, second liveborn litter size, average third and
      fourth total-born and liveborn litter size, number of sows having four litters,
      number of litters per sow, total number of pigs per sow, total number of liveborn
      pigs per sow showed no significant differences between the groups. More (P <
      0.05) sows were culled in outdoor group. Compared to MEC and outdoor housing,
      indoor housed sows suffered higher (P < 0.05) percentage of anoestrus.

PMID- 14643873
TI  - Involvement of multiple transcription factors in the regulation of steroidogenic
      acute regulatory protein gene expression.
AB  - The rate-limiting, committed, and regulatable step in steroid hormone
      biosynthesis is the transport of cholesterol from the outer to the inner
      mitochondrial membrane, a process that is mediated by the steroidogenic acute
      regulatory (StAR) protein. In steroidogenic cells, the StAR protein is regulated
      by cAMP-dependent mechanisms. However, the StAR promoter lacks a consensus cAMP
      response-element (CRE), suggesting the involvement of alternate regulatory
      factor(s) in cAMP responsiveness. These regulatory elements are found to be
      located in a transcription factor-binding site-rich region (consisting of
      approximately 150 nucleotides upstream of the transcription start site) of the
      StAR promoter, and appears to be the most important region in regulating
      transcription of the StAR gene. The StAR promoter sequences in mouse, rat and
      human are highly homologous, and in the absence of a canonical CRE, multiple cis
      elements have been shown to be instrumental in the regulation of StAR gene
      expression. Nevertheless, it has become apparent that functional cooperation,
      interaction, and alteration of different transcription factors are involved in
      the fine-tuning of the regulatory events associated with StAR gene transcription.

PMID- 14643874
TI  - Aldosterone and aldosteronism.

PMID- 14643875
TI  - Characterization of [11C]vorozole binding in ovarian tissue in rats throughout
      estrous cycle in association with conversion of androgens to estrogens in vivo
      and in vitro.
AB  - Estrogen levels vary in a cyclic fashion during the rat estrous cycle, reaching
      peak concentrations during proestrus. Previously, it was suggested that the
      preovulatory peak in estrogen production in rats in vivo is regulated by other
      control mechanisms than concentration of precursor and amount of aromatase
      enzyme, changing the specific activity of the enzyme. To explore this hypothesis,
      ovarian binding of [11C]vorozole in vivo and in vitro, representing the amount of
      active aromatase, and conversion activity of ovarian homogenate were assayed
      together with serum androstenedione (A4) and estradiol-17beta (E2) levels during
      the estrous cycle in rats. The reducing ovarian [11C]vorozole binding in vivo
      from proestrus +4 up to +8h might indicate that the ovarian aromatase is blocked,
      probably to prevent premature increase of E2 levels. Thereafter (between
      proestrus +9 and +13h), the binding dramatically increases (aromatase enzyme is
      unblocked), to enable increased E2 synthesis. In addition, during the latter
      period, serum E2 levels were strongly correlated with serum A4 levels after
      adjustment for amount of ovarian aromatase (P=0.03), but not with amount of
      aromatase adjusted for levels of A4 (P=0.13), which might indicate changes in
      specific activity of the aromatase enzyme. Significant correlation between Kd and
      serum E2 levels during the same period indicated that aromatase-precursor
      affinity might be involved in the regulation of the enzyme-specific activity.
      This conclusion is done assuming that [11C]vorozole binding mimics that of the
      substrate (A4). The [11C]vorozole in vivo technique keeps auto- and paracrine
      mechanisms intact, and might therefore yield additional information about
      biological processes compared with traditional in vitro techniques.

PMID- 14643877
TI  - Synthesis of ester-linked lithocholic acid dimers.
AB  - Four lithocholic acid dimers were synthesised via esterification. The ester
      linked dimer, 3-oxo-5beta-cholan-24-oic acid (cholan-24-oic acid methyl ester)-3
      yl ester, (3alpha,5beta), was obtained by condensation of methyl lithocholate
      with 3-oxo-5beta-cholan-24-oic acid. Borohydride reduction of this ester-linked
      dimer gave 3alpha-hydroxy-5beta-cholan-24-oic acid (cholan-24-oic acid methyl
      ester)-3-yl ester, (3alpha,5beta), which was acetylated to 3alpha-acetoxy-5beta
      cholan-24-oic acid (cholan-24-oic acid methyl ester)-3-yl ester, (3alpha,5beta).
      Reaction of methyl lithocholate with oxalyl chloride yielded the oxalate dimer,
      bis(5beta-cholan-24-oic acid methyl ester)-3alpha-yl oxalate.

PMID- 14643876
TI  - Synthesis of hapten and conjugates of coumestrol and development of immunoassay.
AB  - 3-O-Carboxymethylcoumestrol was prepared as the hapten for immunoassay by a
      partial alkylation of coumestrol with ethyl chloroacetate in acetone alkalized
      with potassium carbonate. 3-O-Ethoxycarbonylmethylcoumestrol was separated by
      column chromatography and finally was hydrolyzed with formic acid. 1H and 13C NMR
      data (APT, COSY, HMQC, and HMBC) revealed that the reaction was regioselective,
      as 3-O-ethoxycarboxymethylcoumestrol was the only monosubstituted derivative. The
      hapten was then conjugated to bovine serum albumin and used for immunization of
      rabbits. A radioimmunoassay (RIA) system was established based on the polyclonal
      antiserum and a 125I-labeled hapten-tyrosine methyl ester conjugate as the
      radioligand. Parameters of the RIA: sensitivity: 12 pg per tube, 50% intercept:
      140 pg per tube, working range: 20-4000 pg per tube. The cross-reactivity of a
      panel isoflavonoid and lignan phytoestrogens was either negligible (e.g.
      formononetin 0.07%; biochanin A 0.06%) or not detectable at all. The major
      immunoreactive peak in HPLC fractions from an alfalfa extract had the same
      retention time as coumestrol standard and represented 94.8% of the signal. The
      remaining 5.2% of immunoreactivity was distributed between five minor peaks. We
      conclude that after the validation for particular matrices, the method will be a
      useful tool for analysis of coumestrol, especially in low volume and low
      concentration samples.

PMID- 14643878
TI  - Synthesis of the 7alpha-cyano-(17alpha,20E/Z)-[125I]iodovinyl-19
      nortestosterones: potential radioligands for androgen and progesterone receptors.
AB  - We report the preparation of the 7alpha-cyano derivative of the isomeric
      (17alpha,20E/Z)-[125I]iodovinyl-19-nortestosterones (IVNT) together with their
      binding affinity for the androgen receptor (AR) and their biodistribution in two
      different animal models. The cyano group was introduced at the 7alpha-position by
      hydrocyanation of 4,6-estradien-17beta-ol-3-one with diethylaluminum cyanide.
      Selective protection of the A-ring enone system as the dienol ether followed by
      ethynylation and deprotection under base and acid hydrolysis condition gave
      7alpha-cyano-17alpha-ethynyl-19-nortestosterone. The stannyl derivatives were
      prepared by addition of tri-n-butylstannyl hydride and converted
      stereospecifically to the corresponding [125I]iodovinyl analog using [125I]NaI
      and H2O2. The [125I]iodovinylsteroids were intravenously administered to male
      rats and estrogen-primed immature female rats and tissue uptake was measured up
      to 6h post-injection. Co-administration of NLP-004 or ORG-2058, highly selective
      ligands for the progesterone receptor, to the female rats did not affect uterus
      uptake of the 125I-ligands. However co-injection of testosterone to DES-primed
      male rats induced a marked increase in prostate uptake of the 20Z-isomer of
      7alpha-cyano-[125I]-IVNT. The relative binding affinity (RBA) of either 7alpha
      cyano-(17alpha,20E/Z)-IVNT isomer for the AR is low (RBA=4 and 3, respectively,
      versus 100 for 5alpha-dihydrotestosterone (DHT)), suggesting the absence of a
      possible role of the AR in the localization process. These findings contrast
      previously reported data for the analogous 7alpha-methyl-[125I]-IVNT where co
      administration of testosterone was shown to result in a 50% drop in prostate
      uptake. These data indicate that the addition of an electron withdrawing 7alpha
      cyano group to 123I-labeled nortestosterone derivatives does not improve their
      potential to serve as SPECT agents for the imaging of AR densities in the
      prostate.

PMID- 14643879
TI  - Limitations of direct estradiol and testosterone immunoassay kits.
AB  - Estradiol (E2) and testosterone (T) are biologically active hormones that serve
      as important diagnostic markers in serum of premenopausal and postmenopausal
      women and in men. These hormones are measured frequently by immunoassay in
      clinical laboratories and the test results are used in the diagnosis and
      treatment of patients. For measuring the hormones by immunoassay, most
      laboratories utilize commercially available reagents that are packaged in the
      form of a kit and are used either in an automated instrument or manually.
      However, both the diagnostic kit manufacturer and testing laboratory seldom
      thoroughly validate the assay methods generated with these kits. This deficiency
      may lead to unreliable test results that could affect clinical evaluation and
      treatment of patients. The purpose of the present study was to assess the
      reliability of immunoassays that quantify serum E2 and T levels with commercial
      diagnostic kits. The data generally show wide differences in the apparent levels
      of each hormone in a given sample obtained with kits from different
      manufacturers. This was especially true when measuring postmenopausal E2 and T
      levels. However, a purification step, which included organic solvent extraction,
      prior to radioimmunoassay (RIA) of E2 gave values that compared well with those
      obtained by conventional RIA (with preceding extraction/chromatographic steps).
      Our results point out the importance of more thoroughly validating assays
      performed with commercial immunoassay kits, especially with respect to
      sensitivity and specificity, prior to their use for measuring hormone levels in
      patient samples.

PMID- 14643880
TI  - Androgen receptor isoforms AR-A and AR-B display functional differences in
      cultured human bone cells and genital skin fibroblasts.
AB  - Two isoforms of the androgen receptor (AR-A and AR-B), differing by a lack of the
      first 187 amino acids in the NH2-terminal transactivation domain of AR-A, are
      expressed in connective tissue and bone. Transient transfections of normal human
      osteoblastic cells (HOB) and of genital skin fibroblasts defective in AR (GSF
      540) were utilized to compare the functional properties of AR isoforms in
      mesenchymal tissues. Overexpression of AR-B or AR-A did not significantly affect
      type I collagen secretion. However, overexpression of AR-B (but not AR-A)
      restored androgen-dependent DNA synthesis in AR-defective fibroblasts and
      increased DHT-mediated DNA synthesis three-fold in osteoblastic cells.
      Overexpression of AR-A did not affect DHT action but reduced DHT-dependent DNA
      synthesis when transfected together with AR-B. The need for an NH2-terminal
      sequence of the AR for complete receptor function was demonstrated using
      electrophoretic mobility shift assay. A peptide coding for the amino terminus of
      the complete AR was able to decrease the binding affinity of AR-B and increase
      the binding affinity of AR-A to the androgen response element. Our results
      suggest that AR-A lacks the ability to stimulate cell proliferation possibly due
      to reduced binding of AR co-activating proteins to the truncated N-terminal
      transactivation domain rather than due to impaired stability of the AR-A isoform.

PMID- 14643881
TI  - Synthesis and biological properties of 7alpha-cyano derivatives of the
      (17alpha,20E/Z)-[125I]iodovinyl- and 16alpha-[125I]iodo-estradiols.
AB  - The synthesis, receptor binding affinity, estrogenic potency and tissue
      distribution of the 7alpha-cyano derivatives of the (17alpha,20E/Z)
      [125I]iodovinyl-(CIVE) and 16alpha-[125I]iodo-estradiols (CIE) are reported. The
      iodovinyl derivatives were prepared via the (17alpha,20E/Z)-tri-n-butylstannyl
      intermediates, derived from the addition of tri-n-butyl tin hydride to the
      17alpha-ethynyl group of the 7alpha-cyano-17alpha-ethynylestradiol, using
      triethylborane as a catalyst. The no-carrier-added [125I]-CIVE isomers were
      prepared via the same stereospecific reaction. [125I]-CIE was prepared from
      7alpha-cyano-16beta-bromoestradiol via halogen exchange with Na125I. Addition of
      the 7alpha-cyano group to 16alpha-iodoestradiol did not affect estrogen receptor
      binding affinity (RBA of CIE is 115). However the estrogenic potential of CIE, as
      measured by the capacity to stimulate the expression of the pS2 gene, was reduced
      to 1% as compared to that of estradiol. Addition of a 7alpha-cyano group to the
      (17alpha,20E/Z)-IVE isomers reduced the RBA to 21 and 36, respectively, while the
      estrogenic potential was reduced to 2-3% of that of estradiol. Uterus uptake in
      immature rats of the 125I-labeled CIVE 20E-isomer and the 16alpha-iodo CIE peaked
      at 0.5h post injection while the (17alpha,20Z)-CIVE isomer showed a maximum only
      past 5h post injection. Uptake of all three 125I-labeled 7alpha-cyanoestrogens
      was suppressed by the co-injection of non-radioactive estradiol confirming the
      role of estrogen receptors in the localization process. Uterus retention pattern
      differ substantially from those of the analogues 7alpha-methylestrogens, which
      were previously shown to give high maximum 125I-uptake values at 2h post
      injection. Overall our data indicate that addition of a 7alpha-cyano group to
      123I-labeled estrogens does not improve their potential to serve as SPECT agents
      for the imaging of estrogen receptor densities in breast cancer.

PMID- 14643882
TI  - Neural crest cells: a model for invasive behavior.
AB  - Neural crest cells are the embryonic precursors of the neurons and glia of the
      peripheral nervous system, pigment cells, and connective tissue in the face, neck
      and heart. They are induced near the junction of the neural plate and embryonic
      ectoderm and undergo an epithelial to mesenchymal transition (EMT). Neural crest
      cells then display invasive behavior and migrate into the surrounding tissues
      along specific pathways. Neural crest cells are amenable to study in tissue
      culture, and the molecules that regulate their development can be studied in vivo
      with antisense techniques as well as with the expression of gain and loss-of
      function constructs. Mutations in factors that regulate neural crest cell
      survival or differentiation can lead to cell death or the premature cessation of
      their migration, resulting in craniofacial abnormalities, pigmentation defects
      and the absence of enteric neurons. This paper reviews recent advances in our
      understanding of neural crest cell induction and migration, emphasizing both
      avian and amphibian models. Cell facts: The embryonic progenitors of pigment
      cells, the neurons and glia of the peripheral nervous system, as well as
      connective tissue in the face, neck and heart. Induced to form at the boundary of
      the neuroepithelium and embryonic ectoderm. Expression of the transcription
      factors Snail, Slug and FoxD3 leads to delamination from the neural tube.
      Invasive motility not unlike that of tumor cells can be studied in vitro. Express
      proteases, distinctive cell surface receptors and glycoproteins to acquire an
      invasive phenotype. Mutations of transcription factors expressed by the neural
      crest or in other factors that inhibit their premature differentiation can lead
      to survival and migration-associated birth defects.

PMID- 14643883
TI  - Leukemia: beneficial actions of retinoids and rexinoids.
AB  - Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, is the
      prototype of a cancer that can be cured by differentiation therapy using combined
      retinoic acid (RA) and chemotherapy. Acute promyelocytic leukemia is caused by
      chromosomal translocations, which in the large majority of cases generate the
      prototypic promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARalpha) an
      oncogenic fusion protein formed from the retinoic-acid receptor alpha and the so
      called PML protein. The fusion protein leads to the deregulation of wild type PML
      and RARalpha function, thus inducing the differentiation block and an altered
      survival capacity of promyelocytes of affected patients. A plethora of studies
      have revealed molecular details that account for the oncogenic properties of
      acute promyelocytic leukemia fusion proteins and the events that contribute to
      the therapy-induced differentiation and apoptosis of patients' blasts.
      Illustrating the beneficial mechanisms of action of retinoids for acute
      promyelocytic leukemia patients this review goes on to discuss a plethora of
      recently recognized molecular paradigms by which retinoids and rexinoids, alone
      or in combination with other compounds, regulate growth, differentiation and
      apoptosis also in non-acute promyelocytic leukemia cells, highlighting their
      potential as drugs for cancer therapy and prevention.

PMID- 14643884
TI  - Protein kinase C epsilon: a new target to control inflammation and immune
      mediated disorders.
AB  - Recent advances in understanding the molecular basis for mammalian host immune
      responses to microbial invasion suggest that the first line of defense against
      microbes is the recognition of pathogen-associated molecular patterns by a set of
      germline-encoded receptors: the Toll-like receptors (TLRs). TLRs have been
      identified as being part of a large family of pathogen-recognition receptors that
      play a decisive role in the induction of both innate and adaptive immunity.
      Indeed, activation of T lymphocytes depends on their interaction with dendritic
      cells previously stimulated by TLR agonists such as bacterial lipopolysaccharide
      (LPS), a TLR-4 ligand. A novel PKC epsilon (epsilon) was recently found to be a
      critical component of TLR-4 signaling pathway and thereby to play a key role in
      macrophage and dendritic cell (DC) activation in response to LPS. Thus,
      controlling the kinase activity of PKC epsilon might represent an efficient
      strategy to prevent or treat certain inflammatory disorders of microbial origin.

PMID- 14643885
TI  - The mammalian basic helix-loop-helix/PAS family of transcriptional regulators.
AB  - Basic helix-loop-helix (bHLH)/PAS proteins are critical regulators of gene
      expression networks underlying many essential physiological and developmental
      processes. These include transcriptional responses to environmental pollutants
      and low oxygen tension, mediated by the aryl hydrocarbon (Dioxin) receptor and
      hypoxia inducible factors (HIF), respectively, and controlling aspects of neural
      development, mediated by the single minded (SIM) proteins. bHLH proteins must
      dimerise to form functional DNA binding complexes and bHLH/PAS proteins are
      distinguished from other members of the broader bHLH superfamily by the
      dimerisation specificity conferred by their PAS homology domains. bHLH/PAS
      proteins tend to be ubiquitous, latent signal-regulated transcription factors
      that often recognise variant forms of the classic E-box enhancer sequence bound
      by other bHLH proteins. Two closely related forms of each of the hypoxia
      inducible factors alpha and single minded proteins and the general partner
      protein, aryl hydrocarbon receptor nuclear translocator (ARNT), are present in
      many cell types. Despite high sequence conservation within their DNA binding and
      dimerisation domains, and having very similar DNA recognition specificities, the
      homologues are functionally non-redundant and biologically essential. While the
      mechanisms controlling partner choice and target gene activation that determine
      this functional specificity are poorly understood, interactions mediated by the
      PAS domains are essential. Information on structures and protein/protein
      interactions for members of the steroid hormone/nuclear receptor superfamily has
      contributed to our understanding of the way these receptors function and assisted
      the development of highly specific agonists and antagonists. Similarly, it is
      anticipated that developing a detailed mechanistic and structural understanding
      of bHLH/PAS proteins will ultimately facilitate drug design.

PMID- 14643886
TI  - Damage to the structure of erythrocyte plasma membranes in patients with type-2
      hypercholesterolemia.
AB  - BACKGROUND: Hypercholesterolemia may decrease the deformability of red blood
      cells which impairs their hemorheological behavior and promotes atherosclerosis.
      The study involved 60 hypercholesterolemic patients and 30 healthy individuals as
      the control group. METHODS: The membrane fluidity of erythrocytes was estimated
      by a spin-label method (5-doxylstearic acid (5-DSA)). The ratio of weakly to
      strongly (W/S) immobilized residues of erythrocyte membrane-bond maleimide-tempo
      spin label was studied in oxidative damage to membrane protein. Damage to
      erythrocyte proteins was also indicated by means of Na(+) K(+) ATPase activity.
      RESULTS: The membranes of hyperlipidemia (hlp) patients contain larger
      concentrations of cholesterol 2.16+/-0.24 than do those of the normolipemic
      individuals 0.31+/-0.24 (P<0.001). The level of Na(+) K(+) ATPase in the
      erythrocyte membrane from the control group was higher 103.4+/-1.3
      (nmolPi/(mgproteinsh)) than in the patient group 93.6+/-3.2
      (nmolPi/(mgproteinsh)) (P<0.001). The order parameter S 5-DSA in the control
      group was 0.745+/-0.009 and in hlp patients was 0.755+/-0.009 (P<0.001). The W/S
      ratio in the control group amounted to 2.00+/-0.09 and in the hlp patient group
      was 2.50+/-0.11 (P<0.001). CONCLUSION: Type-2 hypercholesterolemia causes changes
      in the structure and fluidity of erythrocyte plasma membranes since the excess of
      cholesterol affects the normal rheology of blood through its interaction with
      erythrocytes. It also impairs the function and structure of plasma membrane
      proteins.

PMID- 14643887
TI  - Volatile anaesthetics induce biochemical alterations in the heme pathway in a B
      lymphocyte cell line established from hepatoerythropoietic porphyria patients
      (LBHEP) and in mice inoculated with LBHEP cells.
AB  - Hepatoerythropoietic porphyria (HEP) is the homozygous form of Porphyria Cutanea
      Tarda (PCT), characterized by an accumulation of porphyrins due to
      uroporphyrinogen decarboxylase deficiency. Fluorinated volatile anaesthetics are
      often used to produce general anaesthesia. Anaesthesia has certainly been
      implicated in the triggering of acute porphyria crisis. The effects of volatile
      anaesthetics in a B-lymphocyte cell line established from HEP patients (LBHEP) on
      heme metabolism have been investigated.LBHEP cells were exposed to sodium
      phosphate buffer containing dissolved Enflurane, Isoflurane or Sevoflurane (10mM)
      during 20min. Aminolevulinate synthase (ALA-S) activity, the regulatory enzyme of
      heme synthesis, was 300% induced by the anaesthetics. A 25-30% diminution of
      porphobilinogenase (PBG-ase) activity was found when Isoflurane or Sevoflurane
      were added to the cells, while no significant changes were detected after
      Enflurane treatment. Although some oxidative stress has been induced by the
      anaesthetics, reflected by the 35% diminution of glutathione (GSH), no alteration
      in heme oxygenase (HO) activity, the enzyme involved in heme breakdown and
      frequently induced as a response to stress stimuli, was observed. Studies using
      animals inoculated with LBHEP cells were also performed. Findings here described
      mimic biochemical alterations in the heme pathway, which are characteristic of
      another hepatic porphyria, similar to those previously reported when these
      anaesthetics were administered to animals, and they also advertise about the
      possible unsafe use of these drugs in the case of hepatic non-acute porphyrias.

PMID- 14643888
TI  - Caspase-dependent apoptosis and -independent poly(ADP-ribose) polymerase cleavage
      induced by transforming growth factor beta1.
AB  - Apoptosis is an important cell suicide program which involves the caspases
      activation and is implicated in physiological and pathological processes.
      Poly(ADP-ribose) polymerase (PARP) cleavage is often associated with apoptosis
      and has been served as one hallmark of apoptosis and caspase activation. In this
      study, we aimed to determine TGF-beta1-induced apoptosis and to examine the
      involvement of caspases and its relationship with PARP cleavage. TGF-beta1
      induces strong apoptosis of AML-12 cells which can be detected by DNA
      fragmentation, FACS, and morphological assays. Z-VAD-fmk, a selective caspase
      inhibitor, partially inhibits the TGF-beta1-induced apoptosis; but has no effect
      on TGF-beta1-induced DNA fragmentation and PARP cleavage. However, BD-fmk, a
      broad-spectrum caspase inhibitor, completely suppresses TGF-beta1-induced
      apoptosis, but unexpectedly does not inhibit TGF-beta1-induced PARP cleavage.
      Furthermore, Z-VAD-fmk treatment is able to completely inhibit the daunorubicin
      induced apoptosis in A-431 cells, but only slightly blocks the daunorubicin
      induced PARP cleavage, whereas BD-fmk can inhibit both daunorubicin-induced
      apoptosis and PARP cleavage completely. In addition, we observed that both TGF
      beta1-induced apoptosis and PARP degradation in AML-12 cells can be completely
      blocked by inhibiting the protein synthesis with cycloheximide. These results
      demonstrate for the first time that TGF-beta1-induced caspase-dependent apoptosis
      is associated with caspase-independent PARP cleavage that requires the TGF-beta1
      induced synthesis of new proteins. The results indicate that caspase-3 is not a
      major caspase involved in TGF-beta1-induced apoptosis in AML-12 cells, and is not
      required for apoptosis-associated DNA fragmentation. The results also suggest
      that PARP cleavage may occur as an independent event that can be disassociated
      with cell apoptosis.

PMID- 14643889
TI  - Tyrosinase kinetics: discrimination between two models to explain the oxidation
      mechanism of monophenol and diphenol substrates.
AB  - The kinetic behaviour of tyrosinase is very complex because the enzymatic
      oxidation of monophenol and o-diphenol to o-quinones occurs simultaneously with
      the coupled non-enzymatic reactions of the latter. Both reaction types are
      included in the kinetic mechanism proposed for tyrosinase (Mechanism I [J. Biol.
      Chem. 267 (1992) 3801-3810]). We previously confirmed the validity of the rate
      equations by the oxidation of numerous monophenols and o-diphenols catalysed by
      tyrosinase from different fruits and vegetables. Other authors have proposed a
      simplified reaction mechanism for tyrosinase (Mechanism II [Theor. Biol. 203
      (2000) 1-12]), although without deducing the rate equations. In this paper, we
      report new experimental work that provides the lag period value, the steady-state
      rate, o-diphenol concentration released to the reaction medium. The contrast
      between these experimental data and the respective numerical simulations of both
      mechanisms demonstrates the feasibility of Mechanism I. The need for the steps
      omitted from Mechanism II to interpret the experimental data for tyrosinase,
      based on the rate equations previously deduced for Mechanism I is explained.

PMID- 14643890
TI  - Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane
      glutathione.
AB  - Multidrug resistance proteins (MRPs) are ATP-dependent export pumps that mediate
      the export of organic anions. ABCC1 (MRP1), ABCC2 (MRP2) and ABCC3 (MRP3) are all
      able to facilitate the efflux of anionic conjugates including glutathione (GSH),
      glucuronide and sulfate conjugates of xenobiotics and endogenous molecules.
      Earlier studies showed that ABCC4 functions as an ATP-driven export pump for
      cyclic AMP and cyclic GMP, as well as estradiol-17-beta-D-glucuronide. However,
      it was unclear if other conjugated metabolites can be transported by ABCC4. Hence
      in this study, a fluorescent substrate, bimane-glutathione (bimane-GS) was used
      to further examine the transport activity of ABCC4. Using cells stably
      overexpressing ABCC4, this study shows that ABCC4 can facilitate the efflux of
      the glutathione conjugate, bimane-glutathione. Bimane-glutathione efflux
      increased with time and >85% of the conjugate was exported after 15min. This
      transport was abolished in the presence of 2.5microM carbonylcyanide m
      chlorophenylhydrasone (CCCP), an uncoupler of oxidative phosphorylation.
      Inhibition was also observed with known inhibitors of MRP transporters including
      benzbromarone, verapamil and indomethacin. In addition, 100microM methotrexate,
      an ABCC4 substrate or 100microM 6-thioguanine (6-TG), a compound whose
      monophosphate metabolite is an ABCC4 substrate, reduced efflux by >40%. A
      concentration-dependent inhibition of bimane-glutathione efflux was observed with
      1-chloro-2,4-dinitrobenzene (CDNB) which is metabolized intracellularly to the
      glutathione conjugate, 2,4-dinitrophenyl-glutathione (DNP-GS). The determination
      that ABCC4 can mediate the transport of glucuronide and glutathione conjugates
      indicates that ABCC4 may play a role in the cellular extrusion of Phase II
      detoxification metabolites.

PMID- 14643891
TI  - Alkylation of myotoxic phospholipases A2 in Bothrops moojeni venom: a promising
      approach to an enhanced antivenom production.
AB  - Bothrops moojeni crude venom (MjCV) and its two major toxins, namely myotoxin I
      (MjTX-I) and myotoxin II (MjTX-II) were alkylated by p-bromophenacyl bromide
      (BPB). After alkylation the i.p. LD(50) (mice) of MjCV and MjTX-I/II increased
      from 6.0 to 15.7mg/kg and from 8.0 to 45.0mg/kg, respectively. In addition, doses
      of 5x LD(50) of alkylated MjTX-I did not cause a single death in mice and no
      myonecrosis was detected for the alkylated toxins, although both proteins still
      induced edema. Antibodies to native and modified crude venom or myotoxins cross
      reacted with 12 purified class II myotoxic phospholipases A(2) found in snake
      venoms of the genus Bothrops. Myotoxic PLA(2)s from class I and class III were
      not recognized by the above antibodies. These results suggest that the overall
      antigenic structure is conserved among class II myotoxic PLA(2)s, despite
      differences in their amino acid sequences. Anti-MjTX-I-BPB and anti-MjTX-II-BPB
      rabbit serum, obtained against the modified myotoxins, were apparently more
      efficient than those obtained against the native myotoxins. In neutralization
      experiments, pre-incubation of crude venom or isolated myotoxins with antibodies
      raised against the native or modified toxins inhibited their PLA(2) and myotoxic
      activities. Therefore, alkylation of His48 by BPB strongly reduces the local
      tissue damage induced by B. moojeni venom or isolated myotoxins while retaining
      antigenicity, which suggests a promising procedure for an enhanced antiophidian
      serum production for practical purposes.

PMID- 14643892
TI  - Mutational analysis of the large periplasmic loop 7-8 of the putrescine
      transporter PotE in Escherichia coli.
AB  - The PotE protein is a putrescine-ornithine antiporter found in many gram-negative
      bacteria. It is a member of the APA family of transporters and has 12 predicted
      alpha-helical transmembrane spanning segments (TMS). While the substrate binding
      site has previously been mapped to a region near the surface of the cytoplasmic
      lipid layer, no structural feature within the periplasmic domains of PotE have
      been shown to be important for function. We examined the role of the only large
      outer loop, situated between transmembrane spanning segment 7 and 8, in
      putrescine uptake. Deletion of the highly conserved amino acids in the region
      closest to transmembrane spanning segment 7 produced a protein with little
      activity. Glycine-scanning mutagenesis of this region showed that Val(249) and
      Leu(254) were required for optimal transporter function. The V249G mutant
      transported putrescine at a lower maximal rate compared to wild-type (WT) but
      with the same substrate binding affinity. In contrast, the L254G mutant had a
      higher substrate affinity. A series of Val(249) mutants indicated that the
      hydrophobicity of this residue, which is located at or near the membrane surface,
      is important for PotE function. Secondary structure predictions of the large
      outer loop indicated the presence of a hydrophobic alpha-helix in the centre with
      a hydrophobic region at each end suggesting that the loop was not entirely
      exposed to the aqueous periplasmic space. The study shows that loop 7-8 is
      important for PotE function, possibly by forming a re-entrant loop in the channel
      of the transporter.

PMID- 14643893
TI  - The major splice variant of human 5-aminolevulinate synthase-2 contributes
      significantly to erythroid heme biosynthesis.
AB  - The initial step of the heme biosynthetic pathway in erythroid cells is catalyzed
      by an erythroid-specific isoform of 5-aminolevulinate synthase-2 (ALAS2).
      Previously, an alternatively spliced mRNA isoform of ALAS2 was identified
      although the functional significance of the encoded protein was unknown. We
      sought to characterize the contribution of this ALAS2 isoform to overall
      erythroid heme biosynthesis. Here, we report the identification of three novel
      ALAS2 mRNA splice isoforms in addition to the previously described isoform
      lacking exon 4-derived sequence. Quantitation of these mRNAs using ribonuclease
      protection experiments revealed that the isoform without exon 4-derived sequence
      represents approximately 35-45% of total ALAS2 mRNA while the newly identified
      transcripts together represent approximately 15%. Despite the significant amounts
      of these three new transcripts, their features indicate that they are unlikely to
      substantially contribute to overall mitochondrial ALAS2 activity. In contrast, in
      vitro studies show that the major splice variant (lacking exon 4-encoded
      sequence) produces a functional enzyme, albeit with slightly reduced activity and
      with affinity for the ATP-specific, beta subunit of succinyl CoA synthase,
      comparable to that of mature ALAS2. It was also established that the first 49
      amino acids of the ALAS2 pre-protein are necessary and sufficient for
      translocation across the mitochondrial inner membrane and that this process is
      not affected by the absence of exon 4-encoded sequence. We conclude that the
      major splice isoform of ALAS2 is functional in vivo and could significantly
      contribute to erythroid heme biosynthesis and hemoglobin formation.

PMID- 14643894
TI  - The guanidine like effects of arginine on aminoacylase and salt-induced molten
      globule state.
AB  - Aminoacylase is a dimeric enzyme containing one Zn(2+) ion per subunit. The
      arginine (Arg)-induced unfolding of Holo-aminoacylase and Apo-aminoacylase has
      been studied by measurement of enzyme activity, fluorescence emission spectra and
      1-anilino-8-naphthalenesulfonate (ANS) fluorescence spectra. Besides being the
      most alkaline amino acid, the arginine molecule contains a positively charged
      guanidine group, similar to guanidine hydrochloride, and has been used in many
      refolding systems to suppress protein aggregation. Our results showed that
      arginine caused the inactivation and unfolding of aminoacylase, with no
      aggregation during denaturation. A comparison between the unfolding of
      aminoacylase in aqueous and HCl (pH 7.5) arginine solutions indicated that the
      guanidine group of arginine had protein-denaturing effects similar to those of
      guanidine hydrochloride, which might help us understand the mechanism by which
      arginine suppresses incorrect refolding. The results showed that arginine
      denatured aminoacylase could be reactivated and refolded correctly, indicating
      that arginine is as good a denaturant as the guanidine or urea for study of
      protein unfolding and refolding. Both the intrinsic fluorescence and the ANS
      fluorescence spectra showed that the arginine-unfolded aminoacylase formed a
      molten globule state in the presence of KCl, suggesting that intermediates exist
      during aminoacylase refolding. The results for the Apo-aminoacylase followed were
      similar to those for the Holo-enzyme, suggesting that Holo- and Apo-aminoacylase
      might have a similar unfolding and refolding pathway.

PMID- 14643895
TI  - Expression of hyaluronic acid in N-nitrosodimethylamine induced hepatic fibrosis
      in rats.
AB  - Hyaluronic acid (HA) plays prominent role in the pathogenesis of liver fibrosis.
      The mechanism of increased serum and liver HA during hepatic fibrosis was studied
      in rats. Liver injury was induced by intraperitoneal injections of N
      nitrosodimethylamine (NDMA) for 7 consecutive days. A group of animals were
      sacrificed on everyday during injection and also on days 14 and 21 after the
      start of NDMA administration. The alpha-smooth muscle actin (alpha-SMA) was
      stained as a marker for activated stellate cells. Liver HA was studied by
      histochemical methods and serum HA was monitored by HA binding protein assay.
      CD44 was stained immunohistochemically. After the start of NDMA administration,
      necrosis was initiated on day 3 and massive necrosis was observed on days 5 and
      7. Fibrosis was developed on day 14 and early cirrhosis was present on day 21.
      Staining of alpha-SMA demonstrated activated stellate cells from day 3 onwards.
      Serum HA peaked on day 7 and reduced afterwards. Serial liver sections stained
      for HA revealed excessive accumulation of HA during NDMA administration. On days
      14 and 21, alpha-SMA and HA staining was remarkable in fibrotic and cirrhotic
      areas. CD44 staining was negative except during necrosis. It is concluded that
      the early elevation of serum HA is due to the increased synthesis and
      simultaneous release from the necrotic liver. In latter stages the increase of
      both serum and liver HA is contributed by the increased synthesis by the
      activated stellate cells and reduced clearance by the impaired sinusoidal
      endothelial cells.

PMID- 14643896
TI  - Nutritional regulation of lipoprotein lipase in mice.
AB  - Tissue-specific regulation of lipoprotein lipase (LPL) has been extensively
      studied in rats. The mouse is now the most used animal in lipoprotein research,
      and we have therefore explored the regulation of LPL in this species. In C57
      black mice, fed ad libitum adipose tissue LPL activity changed about three-fold
      with the time of day, indicating a circadian rhythm. The highest activity was at
      midnight and the lowest activity was at noon. Withdrawal of food did not markedly
      accelerate the drop of activity that occurred from midnight until noon, but
      prevented the return of activity that occurred during the evening and early
      night. When food was returned to mice that had been fasted for 24h, adipose
      tissue LPL activity rose rapidly and returned to the fed level in 2h. LPL mass in
      adipose tissue changed less than LPL activity, indicating that regulation is
      mainly post-translational as previously demonstrated for rats. When transcription
      was blocked in fasted mice, adipose tissue LPL activity increased, as previously
      observed in rats. LPL activity in heart was highest early in the light period at
      9:00h and lowest at 21:00h. The change was, however, only about 30%. Heparin
      releasable LPL activity in heart was 1.8-fold higher in mice fasted for 6h
      compared to fed controls. We conclude that LPL activity responds to the
      nutritional state in the same direction and by the same mechanisms in mice as in
      rats, but the magnitude of the changes are less in mice.

PMID- 14643897
TI  - Prophylactic and therapeutic treatments with AT 1 and AT 2 receptor antagonists
      and their effects on changes in the severity of pancreatitis.
AB  - Previous studies showed that a local pancreatic renin-angiotensin system (RAS)
      was upregulated in experimental acute pancreatitis. RAS inhibition could
      attenuate pancreatic inflammation and fibrosis, which casts a new light on the
      role of the pancreatic RAS in pancreatitis. The present study explores the
      prophylactic and therapeutic potentials, and possible molecular mechanism for the
      antagonism of angiotensin II receptors on the changes in the severity of
      pancreatic injury induced by acute pancreatitis. Experimental pancreatitis was
      induced by an intraperitoneal injection of supra-maximal dose of cerulein. The
      differential effects of angiotensin II receptors inhibitors losartan and PD123319
      on the pancreatic injury were assessed by virtue of using the pancreatic water
      content, biochemical and histological analyses. Blockade of the AT(1) receptor by
      losartan at a dose of 200microg/kg could markedly ameliorate the pancreatic
      injury induced by cerulein, as evidenced by biochemical and histopathological
      studies. However, blockade of the AT(2) receptor by PD123319 appeared not to
      provide any beneficial role in cerulein-induced pancreatic injury. Both
      prophylactic and therapeutic treatments with losartan were effective against
      cerulein-induced pancreatic injury. The protective action of losartan was linked
      to an inhibition of NAD(P)H oxidase activity, thus consequential oxidative
      modification of pancreatic proteins in the pancreas. Inhibition of the AT(1)
      receptor, but not AT(2) receptor, may play a beneficial role in ameliorating the
      severity of acute pancreatitis. The differential effects of AT(1) and AT(2)
      inhibitors on cerulein-induced pancreatic injury might be due to the distinctive
      mechanism of the AT(1) and AT(2) receptors on the activation of NAD(P)H oxidase.
      Thus the protective role of AT(1) receptor antagonist, losartan, could be
      mediated by the inhibition of NAD(P)H oxidase-dependent generation of reactive
      oxygen species (ROS).

PMID- 14643898
TI  - Recycling, degradation and sensitivity to the synergistic anion of transferrin in
      the receptor-independent route of iron uptake by human hepatoma (HuH-7) cells.
AB  - To secure iron from transferrin, hepatocytes use two pathways, one dependent on
      transferrin receptor (TfR 1) and the other, of greater capacity but lower
      affinity, independent of TfR 1. To clarify further similarities and differences
      of the two pathways, we have suppressed TfR 1 by 75-80% in human hepatoma-derived
      HuH-7 cells co-transfected with vectors bearing full-length TfR 1 cDNA or its
      first 100 bases in antisense orientation. Suppression of TfR 1 does not lead to
      down regulation of TfR 2, a recently described second transferrin receptor of as
      yet uncertain function. Both pathways depend on acidification of the compartments
      in which iron release from transferrin takes place. Recycling of transferrin is a
      feature of both pathways, but is substantially more efficient in the receptor
      dependent route. Degradation of transferrin occurs only in the receptor
      independent route, in the first example of a specific catabolic pathway of
      transferrin. Linkage of cellular iron uptake to release of the synergistic anion
      (without which iron is not bound by transferrin) is particularly evident in the
      receptor-independent pathway. Although the relative importance of the two
      pathways in normal and deranged hepatic iron metabolism remains to be determined,
      the receptor-independent route is a substantial accessory for iron uptake to the
      better-known receptor-dependent track.

PMID- 14643900
TI  - Does high plant feed magnesium and potassium protect healthy ruminants from
      atherosclerosis? A review.
AB  - The literature data were surveyed to clarify the role of magnesium and potassium
      in the development of atherosclerosis (AS) in cows and the findings were compared
      with human data. Special attention was paid to the eastern Finland where AS is
      very common in humans and absent in the cattle. A hypothesis is proposed that
      high magnesium and potassium intakes at plant feeding protect from severe AS
      processes at least in cows in the absence of chronic infections. In about 1500
      necropsies in calves and cows on plant feeding, neither antemortem clinical AS
      symptoms nor postmortal macroscopical AS were detected in the endocardium or in
      aorta. Also, abattoiries in endemic selenium- and vitamin E-deficient areas
      report that no macroscopic AS have been found in the inspected more than 400000
      slaughtered cattle. In vitamin D(3) poisoned cows AS is readily detected. The
      milk-fed calves in magnesium deficiency experiments regularly show AS after 3
      months of age. Adult ruminating cattle get daily 150-300 g potassium while the
      need is 35 g. During the indoor feeding period the cows suffered in eastern
      Finland often from carotene, vitamin E and selenium deficiencies as well as also
      of energy, protein, phosphorus and zinc deficiencies before grass ensiling
      feeding started. Endemic goiter prevalence was about 30%. Still such cows did not
      have AS under such unfavorable conditions. The findings support the hypothesis
      that the high magnesium and potassium intakes protect cows from AS.

PMID- 14643899
TI  - Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I
      gel cultures: regulation by NF-kappaB, AP-1 and Sp1.
AB  - Chronic liver injury leads to a progressive wound healing response that
      eventually results in hepatic fibrosis characterised by net deposition of
      fibrillar extracellular matrix (ECM) and a qualitative shift from type IV to type
      I/III collagen. The pivotal cellular event underlying this response is hepatic
      stellate cell (HSC) activation towards a myofibroblast-like phenotype. Activated
      HSC contribute to ECM remodelling via secretion of type I/III collagens and
      matrix metalloproteinases (MMPs). Previous studies showed that three-dimensional
      (3D) contact of activated HSC with type I collagen further stimulates the ECM
      remodelling properties of HSC by inducing the type IV gelatinase, MMP-9. The aim
      of the current study was to confirm transcriptional activation of the MMP-9 gene
      and identify transcription factors regulating this response. Gelatin zymography
      and Northern blotting were used to confirm induction of MMP-9 protein and mRNA
      expression in primary rat HSC cultured in a three-dimensional collagen I gel
      lattice. MMP-9 promoter studies in transfected HSC and electrophoretic mobility
      shift assay (EMSA) were employed to study transcriptional events. Both NF-kappaB
      and AP-1 DNA were induced in HSC cultured in 3D collagen I gels and binding sites
      for these factors in the MMP-9 promoter were crucial for induction of
      transcription. By contrast removal of an Sp1 site in the promoter enhanced
      transcription, while over-expression of either Sp1 or Sp3 repressed
      transcription. It is concluded that 3D contact of activated HSC with collagen I
      stimulates MMP-9 expression by elevating NF-kappaB and AP-1 activities which are
      able to overcome the repressive influence of Sp1/Sp3 on MMP-9 gene transcription.

PMID- 14643901
TI  - Hypothermia and stroke: the pathophysiological background.
AB  - Hypothermia to mitigate ischemic brain tissue damage has a history of about six
      decades. Both in clinical and experimental studies of hypothermia, two principal
      arbitrary patterns of core temperature lowering have been defined: mild (32-35
      degrees C) and moderate hypothermia (30-33 degrees C). The neuroprotective
      effectiveness of postischemic hypothermia is typically viewed with skepticism
      because of conflicting experimental data. The questions to be resolved include
      the: (i) postischemic delay; (ii) depth; and (iii) duration of hypothermia.
      However, more recent experimental data have revealed that a protected reduction
      in brain temperature can provide sustained behavioral and histological
      neuroprotection, especially when thermoregulatory responses are suppressed by
      sedation or anesthesia. Conversely, brief or very mild hypothermia may only delay
      neuronal damage. Accordingly, protracted hypothermia of 32-34 degrees C may be
      beneficial following acute cerebral ischemia. But the pathophysiological
      mechanism of this protection remains yet unclear. Although reduction of
      metabolism could explain protection by deep hypothermia, it does not explain the
      robust protection connected with mild hypothermia. A thorough understanding of
      the experimental data of postischemic hypothermia would lead to a more selective
      and effective clinical therapy. For this reason, we here summarize recent
      experimental data on the application of hypothermia in cerebral ischemia, discuss
      problems to be solved in the experimental field, and try to draw parallels to
      therapeutic potentials and limitations.

PMID- 14643902
TI  - Correlations between carbohydrate metabolism and corticotrop axis parameters in
      anorexia nervosa.
AB  - The hypercortisolism is one of the hormonal features of anorexia nervosa (AN) in
      the undernutrition phase. This abnormality seems to be related to the nutritional
      factors because the weight restoration leads to the normalization of cortisol. We
      have investigated glycemia, plasma insulin and C-peptide like markers of
      carbohydrate metabolism, and, also, adrenocorticotrope hormone (ACTH), beta
      endorphins and cortisol in basal and dynamics conditions in 142 patients with AN.
      Insulin negatively correlated with the values of cortisol at 16:00 h (r=-0.28,
      P<0.05, N=45); 04:00 h (r=-0.29, P<0.01, N=38). C-peptide negatively correlated
      with the values of cortisol at 08:00 h (r=-0.36, P<0.05, N=36); 12:00 h (r=-0.49,
      P<0.01, N=36); 16:00 h (r=-0.38, P<0.02, N=36); 20:00 h (r=-0.39, P<0.02, N=36);
      04:00 h (r=-0.51, P<0.01, N=31); urinary free cortisol (r=-0.42, P<0.01, N=35);
      dexamethasone suppression test (DST; r=-0.52, P<0.01, N=30). C-peptide negatively
      correlated with the values of ACTH at 08:00 h (r=-0.33, P<0.05, N=37); 24:00 h
      (r=-0.38, P<0.05, N=32); 04:00 h (r=-0.49, P<0.01, N=31); DST (r=-0.45, P<0.02,
      N=25). We did not identify correlations between carbohydrate metabolism indices
      and beta-endorphins. These findings suggest that the nutritional factors may
      cause or maintain the hormonal changes of corticotrop axis in the undernutrition
      states.

PMID- 14643903
TI  - Interaction of exercise training and chronic NOS inhibition on blood pressure,
      heart rate, NO and antioxidants in plasma of rats.
AB  - Many individuals with cardiovascular diseases undergo periodic exercise
      conditioning with or without medication. Therefore, the purpose of this study was
      to examine the effect of exercise training on BP and HR under the condition of
      NOS inhibition and to clarify the mechanism of the effect in regard to oxidative
      stress, antioxidant enzyme activity, and NO production in the plasma of the rat.
      Fisher 344 rats were divided into four groups: (1) sedentary control, (2)
      exercise training for 8 weeks, (3) nitro-L-arginine methyl ester (L-NAME)
      (10mg/kg, s.c. for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) and heart
      rate (HR) were monitored weekly for 8 weeks. The animals were sacrificed 24h
      after last treatments, plasma isolated and analyzed. The results show that
      exercise conditioning resulted in enhanced NO production (120% of control), GSH
      levels (110% of control), GSH/GSSG ratio (124% of control) and the up-regulation
      of catalase (CAT) (225% of control), glutathione peroxidase (GSH-Px) (161% of
      control), glutathione reductase (GR) (142% of control) and glutathione-S
      transferase (GST) (189% of control) and depression of malondialdehyde (MDA) (90%
      of control) and lactate (75% of control) in plasma of the rat. These biochemical
      changes were accompanied by no significant change in BP but slight increase in
      HR. Chronic L-NAME administration resulted in depression of NO (84% of control),
      GSH (90% of control), GSH/GSSG ratio (76% of control), the down-regulation of
      superoxide dismutase (SOD) (67% of control), GST (74% of control), and GR (90% of
      control). Plasma CAT and GSH-Px activities, MDA and lactate levels were
      significantly increased in L-NAME treated rats. The biochemical changes were
      accompanied by increase in blood pressure and heart rate. Interaction of exercise
      training and chronic NOS inhibitor treatment resulted in normalization of plasma
      NO levels, GSH/GSSG ratio, SOD and GST activities, and the up-regulation of, CAT,
      GSH-Px, and GR activities. The interaction resulted in depletion of plasma MDA
      levels compared to L-NAME treated group. The biochemical changes were accompanied
      by decrease in BP and HR compared to L-NAME treated group. The data suggest that
      the exercise training attenuated the oxidative injury caused by NOS inhibitor by
      increasing the plasma NO levels, GSH/GSSG ratio and up-regulating the antioxidant
      enzyme and lowering the BP and HR in the rat.

PMID- 14643904
TI  - Pathophysiology of psoriasis: coping endotoxins with bile acid therapy.
AB  - The authors have tested the hypothesis that the deficiency of bile acids and the
      consequent endotoxin translocation might play a role in the pathogenesis of
      psoriasis. Under normal conditions the bile acids act as detergents (physico
      chemical defense) and can protect the body against enteric endotoxins by
      splitting them into nontoxic fragments and thus preventing the consequent release
      of cytokines [Persp. Biol. Med. 21 (1977) 70]. A total of 800 psoriasis patients
      participated in the study and 551 were treated with oral bile acid (dehydrocholic
      acid) supplementation for 1-8 weeks. The efficacy of the treatment was evaluated
      clinically and also by means of the Psoriasis Area Severity Index (PASI score).
      During this treatment, 434 patients (78.8%) became asymptomatic. Of 249
      psoriatics receiving the conventional therapy, only 62 (24.9%) showed clinical
      recovery during the same period of time (P<0.05). The curative effect of bile
      acid supplementation was more pronounced in the acute form of psoriasis (95.1% of
      the patients became asymptomatic). Two years later, 319 out of the 551 acute and
      chronic psoriasis patients treated with bile acid (57.9%) were asymptomatic,
      compared to only 15 out of the 249 patients (6.0%) receiving the conventional
      treatment (P<0.05). At the end of the 2-year follow-up, only 10 out of 139 acute
      psoriasis patients (7.2%) receiving the conventional therapy and 147 out of 184
      bile acid treated patients (79.9%) were asymptomatic (P<0.01).To conclude, the
      results obtained suggest that psoriasis can be treated with success by oral bile
      acid supplementation presumably affecting the microflora and endotoxins released
      and their uptake in the gut.

PMID- 14643905
TI  - Histochemical assessment of nitric oxide synthase activity in aortic endothelial
      cells of streptozotocin-induced diabetic rats.
AB  - Impaired endothelium-dependent relaxation of blood vessels is a common feature in
      diabetes, but the exact underlying mechanisms have not yet been clarified. In
      present study, endothelium-dependent vasorelaxation of aortic rings were
      evaluated in vitro in streptozotocin (STZ)-induced diabetic and age-matched
      control rats. Moreover, nitric oxide synthase (NOS) activity of aortic
      endothelial cells was assessed in both diabetic and healthy rats using
      histochemical staining for nicotinamide adenine dinucleotide phosphate (NADPH)
      diaphorase activity. The results showed a significant decrease of endothelium
      dependent relaxation in response to acetylcholine (ACh) in diabetic rings,
      compared with controls, that was accompanied by a remarkable attenuation of NOS
      activity in diabetic sections of rat aorta stained for NADPH-diaphorase.
      Furthermore, a membrane disruption of some endothelial cells was also observed in
      all diabetic sections. It can be concluded that a decrease in NOS activity
      together with a disruption of endothelial cell membrane play a major role in
      endothelial dysfunction observed in diabetes.

PMID- 14643906
TI  - Chronic maternal nicotine exposure during gestation and lactation and the
      development of the lung parenchyma in the offspring. Response to nicotine
      withdrawal.
AB  - THE AIM OF THIS STUDY WAS TO INVESTIGATE THE EFFECT OF MATERNAL NICOTINE EXPOSURE
      DURING GESTATION AND LACTATION ON: (1) the development of the gas exchange area
      of the lungs of the offspring; and (2) to determine whether these effects are
      reversible. Pregnant rats received daily nicotine (subcutaneously 1mgkg(-1) body
      weight) during gestation and lactation. Nicotine administration started 1 day
      after mating and lasted until weaning on postnatal day 21. The offspring were
      exposed to nicotine via the placenta and mother's milk only. The lung tissue of
      the neonates was collected on postnatal days 14, 21, 35 and 42 and prepared for
      morphometry. The results obtained show that maternal nicotine exposure resulted
      in bigger alveolar volumes and suppressed alveolarisation in the lungs of the
      offspring. Flattening of the alveoli occurred as the animals aged and as a
      consequence the internal surface area available for gas exchange decreased; a
      condition that resembles panlobular emphysema. It is unlikely that these effects
      of maternal nicotine exposure during gestation and lactation on lung development
      in the offspring was due to a lower birth weight, or a reduction in the period of
      gestation, or a poor supply of nutrients to the offspring. The changes in the gas
      exchange region of the nicotine-exposed rat pups appear to be irreversible.

PMID- 14643907
TI  - Severe myopathy and psychosis in a patient with Cushing's disease macroadenoma.
AB  - Cushing's disease is most commonly caused by a corticotrope adenoma of the
      pituitary. Between 50 and 70% of patients with spontaneous hypercortisolism have
      ACTH-producing pituitary adenomas. The tumors are usually microadenomas with
      approximately 20% of patients with the disease showing no evidence of tumor on CT
      scans or MR imaging of their pituitary glands. In contrast to patients with
      ectopic ACTH production, plasma ACTH concentrations in patients with spontaneous
      disease are generally within the normal range. We describe here a patient with a
      pituitary macroadenoma that showed evidence of necrosis on MRI. The patient had
      an atypical clinical presentation with plasma ACTH levels considerably higher
      than that seen in patients with non-ectopic ACTH-secretory syndrome, markedly
      elevated urine free cortisol, lack of phenotypical signs of hypercortisolism such
      as wide purplish striae, and whose most prominent and distressing symptom was
      severe myopathy that resulted in the patient becoming bed-ridden. Psychosis was
      another striking feature in this patient who during his hospital course developed
      multiple opportunistic infections that contributed to his demise.

PMID- 14643908
TI  - Tacrolimus hydrate (FK506): therapeutic effects and selection of responders in
      the treatment of myasthenia gravis.
AB  - Tacrolimus hydrate (FK506) reduces myasthenic symptoms due to its
      immunosuppressive properties. We studied the therapeutic effects of FK506 and
      noted improvement in 7 of 13 myasthenic patients on the clinical muscle test
      (myasthenia gravis, MG score). Two other patients with relapsing ocular symptoms
      improved. We also examined patient sensitivity to FK506, but could not predict
      such sensitivity before FK506 treatment in the present study.

PMID- 14643910
TI  - Initial predictors of development of pure red cell aplasia in myasthenia gravis
      after thymectomy.
AB  - Pure red cell aplasia (PRCA) is well known to be concomitant with myasthenia
      gravis (MG), but it is difficult to predict the development of PRCA in patients
      with MG. Of 135 patients with MG, four (2.9%) had PRCA. All patients developed
      PRCA after thymectomy during a period when MG was in remission. The frequencies
      of thymoma, bulbar involvement and high anti-acetylcholine receptor (AChR)
      antibody levels were significantly higher in four patients with PRCA. Japanese MG
      patients with these characteristics at presentation were at significant risk for
      the development of PRCA after thymectomy.

PMID- 14643909
TI  - Postoperative communicating hydrocephalus in patients with supratentorial
      malignant glioma.
AB  - Postoperative communicating hydrocephalus in adult patients with supratentorial
      malignant glioma is a relatively uncommon condition that occurs months after the
      initial operation of tumor excision. It occurred in only five of 50 consecutive
      cases treated in our department during the past 10 years. The hydrocephalus
      appeared to be attributable to leptomeningeal dissemination of tumor cells and
      subsequent impairment in cerebrospinal fluid (CSF) absorption. The tumors were
      located adjacent to the lateral ventricles in all five patients, and the
      proximity of the tumor to the cerebral ventricles may have facilitated
      dissemination of the tumor cells into the CSF space, resulting in hydrocephalus.
      The hydrocephalus was treated by a shunt surgery in all five cases, and the
      symptoms temporarily improved. None of the five patients experienced shunt
      malfunction or abdominal symptoms attributable to metastasis to the peritoneal
      cavity, and all five patients died of regrowth of the intracranial tumor or of
      pneumonia.

PMID- 14643911
TI  - Cerebellopontine angle cysticercus and concurrent vascular compression in a case
      of trigeminal neuralgia.
AB  - The authors present the case of a 59-year-old woman with an 8 months history of
      lancinating pain and hyphestesia on the right side of the face along with hearing
      impairment. She had poor tolerance to carbamazepine. A non-enhancing cystic image
      was observed at the right cerebellopontine angle on magnetic resonance imaging.
      The patient underwent surgery. Through a right retromastoid minicraniectomy and
      under microscopic magnification the VII and VIII cranial nerve complex was found
      involved by multiple adhesions around a cysticercus. After the cyst was removed a
      loop of the anteroinferior cerebellar artery was identified compressing the V
      right nerve at its root entry zone. Decompression was performed by the insertion
      of a Teflon implant. The postoperative course was uneventful and trigeminal
      neuralgia (TN) disappeared after surgery. Five previous cases of cranial nerve
      hyperactive dysfunction syndromes, four of trigeminal neuralgia and one of
      hemifacial spasm associated to cerebellopontine angle cysticercosis are briefly
      commented. We suggest that in some of these cases microvascular compression was
      probably present, and during surgery of cerebellopontine angle cysticercus by
      either trigeminal neuralgia or hemifacial spasm, vascular compression must be
      carefully searched and treated when found.

PMID- 14643912
TI  - Iron deficiency anemia and restless legs syndrome: is there an
      electrophysiological abnormality?
AB  - OBJECTIVE: The pathogenesis of restless legs syndrome (RLS) is unknown. Although
      iron deficiency anemia (IDA) is related with RLS, the mechanism of this
      relationship is still unknown. Therefore, we decided to examine some
      neurophysiological parameters that reflect the function of brainstem, spinal cord
      and peripheral nervous system. MATERIALS AND METHODS: 34 patients diagnosed with
      IDA at the hematology department were questioned with a structured battery for
      RLS and additional symptoms. Of those, 14 patients had symptoms of RLS, while
      remaining 20 had no signs of this disorder. In both groups, electrophysiological
      examination including motor and sensory nerve conduction, F-responses, H-reflex,
      blink-reflex, and mixed nerve silent periods was performed. RESULTS: Neurological
      examination of all patients was normal. The two groups were identical for age and
      sex, and the difference between both groups concerning motor and sensory nerve
      conduction, F-wave, H-reflex, blink-reflex, and mixed nerve silent periods was
      insignificant. CONCLUSION: Results suggest that IDA does not cause
      electrophysiological changes in the peripheral nerves, spinal cord and brainstem,
      and therefore, measurement of these parameters in IDA patients does not seem
      effective for the confirmation of RLS.

PMID- 14643913
TI  - MR demonstration of partial lesions of the lateral geniculate body and its
      functional intra-nuclear topography.
AB  - Two rare cases with a partial lesion of the lateral geniculate body (LGB)
      presumably due to ischemia are demonstrated on high resolution MR imaging. A 62
      year-old woman (case 1) presented with left homonymous superior quadrantanopia on
      Goldmann perimetry. Heavily T2 weighted MR images showed a localized lesion at
      the lateral portion of the LGB. The visual field defect was macular and
      horizontal meridian sparing and persisted for 9 years. A 49-year-old woman (case
      2) presented with a sudden onset of left homonymous horizontal sectoranopia on
      Humphrey automated perimetry and heavily T2 weighted images demonstrated a lesion
      localized at the more medial part of the right LGB. Axons originating from
      inferior, central and superior retina are essentially located laterally,
      centrally and medially, respectively, in the LGB, based on the
      electrophysiological studies of animal experiments and this observation has been
      applied to humans. This study radiologically shows that a discrete lateral lesion
      of the LGB produced homonymous upper quadrantanopia in case 1, whereas a more
      medially located lesion produced homonymous sectoranopia in case 2, and reveals
      that the axons originating from inferior retina are located more laterally than
      those from central retina in the human LGB.

PMID- 14643914
TI  - "Occult" ruptured cerebral aneurysms revealed by repeat angiography: result from
      a large retrospective study.
AB  - Not infrequently, cerebral angiography performed immediately after the onset of
      subarachnoid hemorrhage (SAH) fails to reveal any causative lesion. Although the
      cause of the SAH in most of these cases remains unknown, repeat angiography
      sometimes discloses a lesion not detected by the initial angiography. The
      frequency of finding a ruptured aneurysm by repeat angiography and the
      angiographic characteristics of such aneurysms have been investigated
      retrospectively. Nineteen among 316 non-traumatic SAH patients (6%) showed
      initially negative angiogram, and 7 of 19 patients (36%) were identified as
      harboring an "initially occult" aneurysm. It was possible to identify the
      expected cause of these initial false-negative angiograms in four of those seven
      patients. The aneurysm was located in the anterior communicating artery (ACoA)
      complex in four of the seven patients. When interpreting the angiograms of
      patients with SAH, neurologists and neurosurgeons should bear in mind the finding
      that the ACoA complex is the most frequent site of "initially occult" aneurysms.
      One patient had a dissecting aneurysm of the internal carotid artery, and
      although such lesions have been considered rare, they should be included in the
      differential diagnosis of SAH of unknown origin.

PMID- 14643915
TI  - Multicentric glioblastoma multiforme determined by positron emission tomography:
      a case report.
AB  - The actual incidence of true multicentric glioblastoma multiforme (GBM) varies
      between 2.4 and 4.9% of all GBMs. True multicentric tumors are described as
      widespread lesions in different lobes or hemispheres, which cannot be explained
      by spreading along the cerebrospinal fluid or blood pathways. We present here a
      case of multicentric GBM identified with positron emission tomography. CASE
      REPORT: A 73-year-old woman with sudden onset headaches, balance problems, and
      one episode of syncope was diagnosed as having an irregular, contrast-enhancing,
      space-occupying lesion in the left-temporal-parietal region on magnetic resonance
      imaging (MRI). The tissue diagnosis was confirmed as GBM, and she received
      stereotactic radiosurgery using the Leksell Gamma Knife (Elekta Instruments,
      Atlanta, GA). A 3-month, follow-up, MRI scan showed a remarkable decrease in the
      size of the contrast-enhancing area that was targeted during radiosurgery. A
      suspicious area of enhancement was detected on the right side, although no
      surrounding edema was evident. Fluorodeoxyglucose (FDG)-PET scanning revealed a
      large irregular neoplasm extending from the inferior left-temporal lobe into the
      deep parietal lobe with extremely intense FDG uptake, suggesting a very
      aggressive tumor. A smaller lesion was also discovered in the deep right-frontal
      lobe, representing a second neoplastic focus. The patient refused any further
      treatment. CONCLUSION: PET scans, in conjunction with MRI scans, allow for the
      best possible and most comprehensive diagnosis and treatment plans.

PMID- 14643916
TI  - Cervical dystonia mimicking dropped-head syndrome after radiotherapy for
      laryngeal carcinoma.
AB  - We report a case of cervical dystonia mimicking dropped-head syndrome (DHS) in a
      57-year-old man treated for laryngeal carcinoma by radiotherapy (74.4 Gy) 3
      months before. Cervical computerized tomographic scan and magnetic resonance
      imaging (MRI) did not find any muscle fat changes but found a high-intensity
      signal on T2 weighted images in the cervical spinal cord. Clinical and
      electromyographic findings were consistent with cervical dystonia. A trapezius
      biopsy was normal. Spontaneous remission of the dystonia was observed for 1 month
      whereas the laryngeal carcinoma progressed. The link between cervical dystonia
      and radiotherapy might be acute radiation-induced damage to the cervical spinal
      cord.

PMID- 14643917
TI  - Yawning despite trismus in a patient with locked-in syndrome caused by a
      thrombosed megadolichobasilar artery.
AB  - We report a 62-year-old woman with a locked-in syndrome with bilateral
      masticatory spasms and persistent trismus, who was still able to yawn. A vascular
      malformation of the basilar artery-megadolichobasilar artery (fusiform aneurysm,
      vertebrobasilar dolichoectasia) was determined to be the underlying cause of this
      rare combination of symptoms. A thrombus in the megadolichobasilaris as well as
      an almost total pontine infarction were demonstrated on CT- and MRI-scans. Thus,
      trismus may be associated with locked-in syndrome due to megadolichobasilar
      artery thrombus, although yawning is still possible.

PMID- 14643918
TI  - Complicated paraneoplastic neurological syndromes: a report of two patients with
      small cell or non-small cell lung cancer.
AB  - Paraneoplastic neurological syndromes are frequently associated in patients with
      small cell lung cancer (SCLC) and antineuronal antibodies are involved in the
      autoimmune mechanism. Multiple syndromes are sometimes complicated in a single
      patient with SCLC. However, little is known about non-SCLC-associated
      neurological manifestations. We report two patients with complicated
      paraneoplastic neurological syndromes. Patient 1 showed paraneoplastic limbic
      encephalitis (PLE), paraneoplastic sensory neuropathy (PSN) and Lambert-Eaton
      myasthenic syndrome (LEMS) associated with SCLC. Patient 2 developed opsoclonus
      ataxia and probable PLE associated with non-SCLC. Analysis of various
      antineuronal antibodies revealed that anti-Hu and P/Q-type voltage-gated calcium
      channel (VGCC) antibodies were positive in Patient 1 but any antibodies were not
      in Patient 2. Brain MRI demonstrated high intensity signals in temporal lobes
      particularly on fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted
      images. These findings suggest that complicated paraneoplastic neurological
      syndromes occur in non-SCLC as well as SCLC and that unidentified antineuronal
      autoantibodies may underlie the pathophysiology.

PMID- 14643919
TI  - Isolated bilateral sixth nerve palsy secondary to metastatic carcinoma: a case
      report with a review of the literature.
AB  - Isolated sixth nerve palsies usually occur in the vasculopathic age group and are
      often associated with diabetes mellitus, hypertension, and atherosclerosis but
      also occur in the presence of skull base tumors. However, isolated bilateral
      sixth nerve palsies are an extremely rare complication of skull base lesions due
      to metastatic neoplasms. A case of a 46-year-old man with metastatic small-cell
      carcinoma of the lung that developed acute bilateral abducens nerve palsies is
      presented. Although this appears to be an isolated case, metastasis to the skull
      base must be included in the differential diagnosis of isolated bilateral sixth
      nerve palsies.

PMID- 14643920
TI  - Bioptically demonstrated Lafora disease without EPM2A mutation: a clinical and
      neurophysiological study of two sisters.
AB  - Lafora disease (LD) is an autosomal recessive inherited form of progressive
      myoclonic epilepsy with dementia and ataxia, usually presenting in the second
      decade of life and inexorably progressing until death. Neuropathological
      hallmarks are Lafora bodies, intracytoplasmic inclusions that can be found in
      neurons and in other tissues. LD gene (EPM2A), mapping on chromosome 6, encodes
      for a tyrosine phosphatase protein called laforin. However, up to 20% cases of LD
      are not genetically linked to chromosome 6. We report two sisters affected from
      bioptically diagnosed LD but without evidence of EPM2A mutation. Although
      familial cases of LD are already reported in literature, our observation leads to
      some considerations on clinical-electrophysiological evolution as well as to
      remark the genetic heterogeneity of this condition. In addition, we report the
      good effect of the Levetiracetam for the treatment of myoclonus in these
      patients, also demonstrated by the electrophysiological findings.

PMID- 14643921
TI  - The ocular ischemic syndrome.
AB  - The ocular ischemic syndrome represents a serious blinding condition due to
      retinal ischemia secondary to hemodynamically significant carotid artery
      stenosis. However, this condition has received little attention in the
      neurological literature and is likely underdiagnosed. We here describe a patient
      with bilateral severe carotid stenosis and progressive visual loss due to ocular
      ischemia. The best management for this condition remains controversial and should
      be established by including these patients into randomized trials of carotid
      surgery.

PMID- 14643922
TI  - Intramedullary subependymoma of the spinal cord: a case report and review of
      literature.
AB  - A case of cervical spine intramedullary subependymoma in a 52-year-old female is
      reported. Also, the relevant literature on the 40 cases reported till date is
      reviewed. Magnetic resonance imaging, even with enhancement, does not show any
      distinctive features making pre-operative diagnosis often difficult. These
      tumours are eccentrically located within the spinal cord, thus enabling complete
      tumour removal in most cases. They are benign with low proliferative potential
      and hence no post-operative radiotherapy should be administered.

PMID- 14643923
TI  - Chronic epidural hematoma of the vertex.
AB  - Epidural hematomas of the cranial vertex can be rarely found in patients victims
      of head trauma. The diagnosis of the vertex hematoma may be delayed by the odd
      location of the bleeding site and the absence of a clear localization
      symptomatology. The current method of choice for investigation of head trauma
      patients, the computed tomography (CT) scans, may also give misleading diagnostic
      clues. Epidural hematomas of the vertex can be also encountered in a chronic
      form, and re-bleeding is possibly the underlying mechanism for the long term
      permanence of the hematoma. We report a case of a patient with a chronic epidural
      hematoma of the cranial vertex with a long interval between the trauma and the
      symptoms onset. We review the current literature focusing on the diagnostic
      pitfalls and forms of treatment of the chronic epidural hematoma of the vertex.

PMID- 14643924
TI  - Theanine and glutamate transporter inhibitors enhance the antitumor efficacy of
      chemotherapeutic agents.
AB  - Biochemical modulation has played an important role in the development of cancer
      chemotherapy. The combined effects of theanine, a specific amino acid in green
      tea, and glutamate transporter inhibitors on the antitumor activity of
      doxorubicin (DOX), were investigated and we clarified the biochemical mechanisms
      of action of these modulators. In M5076 ovarian sarcoma-bearing mice, theanine
      significantly enhanced the inhibitory effect of DOX on tumor growth and increased
      the DOX concentration in the tumor, compared to DOX-alone group. Furthermore, the
      oral administration of theanine or green tea similarly enhanced the antitumor
      activity of DOX. Moreover, the combination of theanine with DOX suppressed the
      hepatic metastasis of ovarian sarcoma. In contrast, an increase in DOX
      concentration was not observed in normal tissues, such as liver and heart.
      Namely, theanine did not enhance, rather it tended to normalize the increase of
      lipid peroxide (LPO) levels and reduction of glutathione peroxidase activity as
      indicators of the DOX-induced side toxicity. On the other hand, in vitro
      experiments proved that theanine inhibited the efflux of DOX from tumor cells,
      supporting a theanine-induced increase in the DOX concentration in tumors in
      vivo. Moreover, theanine significantly inhibited the glutamate uptake by M5076
      cells similar to specific inhibitors. Two astrocytic high-affinity glutamate
      transporters, GLAST and GLT-1, were expressed in M5076 cells. These results
      suggested that the inhibition of DOX efflux was induced by theanine-mediated
      inhibition of glutamate transporters. The reduction in the concentration of
      glutamate in tumor cells caused by theanine induced decreases in the
      intracellular glutathione (GSH) and GS-DOX conjugate levels. As the expression of
      MRP5 in M5076 cells was confirmed, it is suggested that the GS-DOX conjugate was
      transported extracellularly via the MRP5/GS-X pump in M5076 cells and that
      theanine affected this route. Namely, theanine increases the concentration of DOX
      in a tumor in vivo through inhibition of the glutamate transporter via the GS-X
      pump. Similarly, dihydrokainate (DHK) and L-serine-O-sulfate (SOS), specific
      glutamate transporter inhibitors, indicated the enhancement of the DOX antitumor
      activity via inhibition of glutamate uptake. Therefore, we revealed the novel
      mechanism of enhancement of antitumor efficacy of DOX via the inhibition of
      glutamate transporters. Similarly, theanine enhanced the antitumor activities of
      other anthracyclines, cisplatin and irinotecan. Consequently, the modulating
      effect of theanine on the efficacy of antitumor agents is expected to be
      applicable in clinical cancer chemotherapy.

PMID- 14643925
TI  - Dissecting tumor responsiveness to immunotherapy: the experience of peptide-based
      melanoma vaccines.
AB  - Recent years have witnessed important breakthroughs in our understanding of tumor
      immunology. A variety of immunotherapeutic strategies has shown that immune
      manipulation can induce the regression of established cancer in humans. The
      identification of the genes encoding tumor-associated antigens (TAA) and the
      development of means for immunizing against these antigens have opened new
      avenues for the development of an effective anticancer immunotherapy. However, an
      efficient immune response against tumor requires an intricate cross-talk between
      cancer and immune system cells, which is still poorly understood. Only when the
      molecular basis underlying tumor susceptibility to an immune response is
      deciphered could new therapeutic strategies be designed to fit biologically
      defined mechanisms of cancer immune rejection. In this article, we address some
      of the critical issues that have been identified in cancer immunotherapy, in part
      from our own studies on immune therapies in melanoma patients treated with
      peptide-based vaccination regimens. This is not meant to be a comprehensive
      overview of the immunological phenomena accompanying cancer patient vaccination
      but rather emphasizes some emergent findings, puzzling controversies and
      unanswered questions that characterize this complex field of oncology. In
      addition to reviewing the main immunological concepts underlying peptide-based
      vaccination, we also review the available data regarding naturally occurring and
      therapeutically induced anticancer immune response, both at the peripheral and
      intratumoral level. The hypothesized role of innate immunity in predetermining
      tumor responsiveness to immunotherapeutic manipulation is also discussed.

PMID- 14643926
TI  - Sam68, the KH domain-containing superSTAR.
AB  - Sam68 is one of the most studied members of the STAR family of RNA-binding
      proteins since its identification over a decade ago. Since its ascension into
      prominence, enormous progress has been made to unmask the link between the RNA
      binding properties of Sam68 and the regulation of cellular processes including
      signal transduction, cell cycle regulation and tumorigenesis and RNA biogenesis
      in general. In this review we provide a detailed description of the functional
      domains of Sam68 and the possible biological roles that justify its superSTAR
      status.

PMID- 14643927
TI  - Arachidonic acid-activated Na+-dependent Mg2+ efflux in rat renal epithelial
      cells.
AB  - Arachidonic acid (AA), a metabolite of membrane phospholipids, and its
      metabolites are increased in Mg2+ deficiency. We examined whether the
      extracellular Mg2+ concentration affects AA production and whether AA regulates a
      putative Na+-dependent Mg2+ efflux pathway in renal epithelial NRK-52E cells. We
      used the cells cultured in 5 mM Mg2+-containing medium for 2 days because they
      enable us to detect Na+-stimulated Mg2+ efflux that was not observed in normal
      culture medium. Removal of extracellular Mg2+ increased AA release both in the
      absence and presence of extracellular Na+. This was inhibited by methyl
      arachidonyl fluorophosphonate (MAFP, 10 microM), an inhibitor of cytosolic
      phospholipase A) (cPLA2) and Ca2+-independent phospholipase A2 (iPLA2), and
      bromoenol lactone (BEL, 10 microM), an inhibitor of iPLA2. However, LY-311727 (10
      microM), a secretory phospholipase A2 (sPLA2) inhibitor, had no inhibitory
      effect. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that NRK
      52E cells express cPLA2 and iPLA2 mRNAs, but not sPLA2. In the mag-fura 2
      fluorescence measurements, extracellular Mg2+ removal caused slight decrease in
      the intracellular free Mg2+ concentration ([Mg2+]i) in the Na+-free condition.
      The addition of Na+ caused a rapid decrease in [Mg2+]i, indicating the presence
      of a Na+-dependent Mg2+ efflux pathway. The Na+-dependent [Mg2+]i decrease was
      suppressed by MAFP and BEL. On the other hand, AA metabolite inhibitors,
      nordihydroguaiaretic acid (NDGA) (50 microM), indomethacin (10 microM) and 17
      octadecynoic acid (ODYA) (10 microM), enhanced the Na+-dependent [Mg2+]i
      decrease. Furthermore, the addition of exogenous AA (30 microM) enhanced the Na+
      dependent [Mg2+]i decrease, which was significantly inhibited by imipramine (0.1
      mM), a putative Na+/Mg2+-exchanger inhibitor. These results suggest that
      extracellular Mg2+ removal elevates AA release mediated mainly by iPLA2 and that
      AA upregulates the Na+-dependent Mg2+ efflux in NRK-52E cells.

PMID- 14643928
TI  - On the oligomeric state of the red blood cell glucose transporter GLUT1.
AB  - We stripped human red blood cell membranes of cytoskeleton proteins at pH 12
      without reductant, partially solubilized the obtained vesicles by use of
      octaethylene glycol n-dodecyl ether and purified the glucose transporter GLUT1 by
      anion-exchange chromatography followed by sulfhydryl-affinity chromatography,
      which removed most of the nucleoside transporter (NT) and the lipids. Eighty
      percent of the sulfhydryl-bound GLUT1 could be eluted with sodium dodecyl sulfate
      (SDS) indicating that the bound protein was multimeric. Matrix-assisted laser
      desorption ionization-time of flight-mass spectrometry (MALDI-ToF-MS) of the
      trypsinized major SDS-PAGE zone of the purified material identified GLUT1 but no
      other membrane protein. Transmembrane helices 1 and 8 were among the detected
      fragments. The reconstituted purified GLUT1 showed glucose transport activity,
      although only approximately 0.05 high-affinity cytochalasin B (CB) binding sites
      were present per GLUT1 monomer. The vesicles used as starting material for the
      purification showed 0.4 CB sites per GLUT1 monomer, similar to vesicles prepared
      in the presence of dithioerythritol. The data are consistent with the coexistence
      of monomeric GLUT1 with high-affinity CB-binding activity and preferentially
      solubilized multimeric GLUT1 with no CB-binding activity in the red blood cell
      membrane vesicles prepared without reductant.

PMID- 14643929
TI  - Structure-function studies of yeast C-4 sphingolipid long chain base hydroxylase.
AB  - The roles of putative active site residues of the Saccharomyces cerevisiae
      sphingolipid C-4 long chain base hydroxylase (Sur2p) were investigated by site
      directed mutagenesis. The replacement of any one of conserved His residues of
      three histidine-rich motifs with an alanine eliminated hydroxylase activity in
      vivo and in vitro, indicating that they are all essential elements of the active
      site. An additional conserved His residue (His 249) outside of the histidine-rich
      cluster region was also found to be crucial for activity. Additional mutants
      altered in residues in close proximity to the histidine-rich cluster were
      generated. In order to determine their roles in hydroxylase vs. desaturase
      activities, residues were replaced with conserved residues from the yeast Delta7
      sterol-C5(6)-desaturase, Erg3p. Residues Phe 174, Asn 182, Ser 191, Leu 196, Pro
      199, Asn 266, Tyr 269, Asp 271 and Gln 275 appear to be additionally important
      elements of the active site but their conversion into corresponding Erg3p
      residues did not lead to a gain in desaturase activity. It is concluded that
      Sur2p is a membrane-bound hydroxylase that belongs to the diiron family of eight
      histidine motif enzymes.

PMID- 14643930
TI  - Proteorhodopsin in living color: diversity of spectral properties within living
      bacterial cells.
AB  - Proteorhodopsin is a family of over 50 proteins that provide phototrophic
      capability to marine bacteria by acting as light-powered proton pumps. The
      potential importance of proteorhodopsin to global ocean ecosystems and the
      possible applications of proteorhodopsin in optical data storage and optical
      signal processing have spurred diverse research in this new family of proteins.
      We show that proteorhodopsin expressed in Escherichia coli is functional and
      properly inserted in the membrane. At high expression levels, it appears to self
      associate. We present a method for determining spectral properties of
      proteorhodopsin in intact E. coli cells that matches results obtained with
      detergent-solubilized, purified proteins. Using this method, we observe
      distinctly different spectra for protonated and deprotonated forms of 21 natural
      proteorhodopsin proteins in intact E. coli cells. Upon protonation, the
      wavelength maxima red shifts between 13 and 53 nm. We find that pKa values
      between 7.1 and 8.5 describe the pH-dependent spectral shift for all of the 21
      natural variants of proteorhodopsin. The wavelength maxima of the deprotonated
      forms of the 21 natural proteorhodopsins cluster in two sequence-related groups:
      blue proteorhodopsins (B-PR) and green proteorhodopsins (G-PR). The site-directed
      substitution Leu105Gln in Bac31A8 proteorhodopsin shifts this G-PR's wavelength
      maximum to a wavelength maximum the same as that of the B-PR Hot75m1
      proteorhodopsin. The site-directed substitution Gln107Leu in Hot75m1
      proteorhodopsin shifts this B-PR's wavelength maximum to a wavelength maximum as
      that of Bac31A8 proteorhodopsin.

PMID- 14643931
TI  - Action of hypoxia on different types of calcium channels in hippocampal neurons.
AB  - Whole-cell patch clamp and polarographic oxygen partial pressure (pO2)
      measurements were used to establish the sensitivity of high-voltage-activated
      (HVA) Ca2+ channel subtypes of CA1 hippocampal neurons of rats to hypoxic
      conditions. Decrease of pO2 to 15-30 mm Hg induced a potentiation of HVA Ca2+
      currents by 94%. Using selective blockers of N- and L-types of calcium channels,
      we found that inhibition of L-type channels decreased the effect by 54%, whereas
      N-type blocker attenuated the effect by 30%. Taking into account the ratio of
      currents mediated by these channel subtypes in CA1 hippocampal neurons, we
      concluded that both types of HVA Ca2+ channels are sensitive to hypoxia, however,
      L-type was about 3.5 times more sensitive to oxygen reduction.

PMID- 14643932
TI  - Sarcolemmal and mitochondrial effects of a KATP opener, P-1075, in "polarized"
      and "depolarized" Langendorff-perfused rat hearts.
AB  - We investigated consequences of cardiac arrest on sarcolemmal and mitochondrial
      effects of ATP-sensitive potassium channel (KATP) opener, P-1075, in Langendorff
      perfused rat hearts. Depolarised cardiac arrest (24.7 mM KCl) did not affect
      glibenclamide-sensitive twofold activation of rubidium efflux by P-1075 (5
      microM) from rubidium-loaded hearts, but eliminated uncoupling produced by P-1075
      in beating hearts: 40% depletion of phosphocreatine and ATP, 50% increase in
      oxygen consumption, and reduction of cytochrome c oxidase. Depolarized cardiac
      arrest by calcium channel blocker, verapamil (5 microM), also prevented
      uncoupling. Lack of P-1075 mitochondrial effects in depolarized hearts was not
      due to changes in phosphorylation potential, because 2,4-dintrophenol (10 microM)
      reversed the [PCr]/[Cr] increase and Pi decrease, characteristic of KCl-arrest,
      but did not restore uncoupling. In agreement with this conclusion, pyruvate (5
      mM) increased [PCr]/[Cr] and decreased Pi, but did not prevent uncoupling in
      beating hearts. A decrease in mean [Ca2+] in KCl-arrested hearts could not
      account for lack of P-1075 mitochondrial effects, because calcium channel opener,
      S-(-)-Bay K8644 (50 nM), and beta-agonist, isoproterenol (0.5 microM), did not
      facilitate uncoupling. In contrast, in adenosine (1 mM)-arrested hearts
      (polarized arrest), P-1075 caused 40% phosphocreatine and ATP depletion. In
      isolated rat liver mitochondria, P-1075 (20 microM) decreased mitochondrial
      membrane potential (DeltaPsi) by approximately 14 mV (demonstrated by
      redistribution of DeltaPsi-sensitive dye, rhodamine 800) in a glibenclamide
      sensitive manner. We concluded that cell membrane depolarization does not prevent
      activation of sarcolemmal KATP by P-1075, but it plays a role in mitochondrial
      uncoupling effects of P-1075.

PMID- 14643933
TI  - Interaction of a synthetic peptide corresponding to the N-terminus of canine
      distemper virus fusion protein with phospholipid vesicles: a biophysical study.
AB  - The F protein of canine distemper virus (CDV) is a classic type I glycoprotein
      formed by two polypeptides, F1 and F2. The N-terminal regions of the F1
      polypeptides of CDV, measles virus and other paramyxoviruses present moderate to
      high homology, supporting the existence of a high conservation within these
      structures, which emphasises its role in viral-host cell membrane fusion. This N
      terminal polypeptide is usually termed the fusion peptide. The fusion peptides of
      most viral fusion-mediating glycoproteins contain a high proportion of
      hydrophobic amino acids, which facilitates its insertion into target membranes
      during fusion. In this work we report on the interaction of a 31-residue
      synthetic peptide (FP31) corresponding to the N terminus of CDV F1 protein with
      phospholipid membranes composed of various phospholipids, as studied by means of
      various biophysical techniques. FTIR investigation of FP31 secondary structure in
      aqueous medium and in membranes resulted in a major proportion of alpha-helical
      structure which increased upon membrane insertion. Differential scanning
      calorimetry (DSC) showed that the presence of concentrations of FP31 as low as
      0.1 mol%, in mixtures with L-alpha-dimyristoylphosphatidylcholine (DMPC), L-alpha
      dipalmitoylphosphatidylcholine (DPPC) and L-alpha-distearoylphosphatidylcholine
      (DSPC), already affected the thermotropic properties of the gel to liquid
      crystalline phase transition. In mixtures with the three lipids, increasing the
      concentration of peptide made the pretransition to disappear, and lowered and
      broadened the main transition. This effect was slightly stronger as the acyl
      chain length of the phospholipid grew larger. In the corresponding partial phase
      diagrams, no immiscibilities or critical points were observed. FTIR showed that
      incorporation of 1 mol% of peptide in DPPC shifted the antisymmetric and
      symmetric CH2 stretching bands to higher values, indicating the existence of an
      additional disordering of the acyl chain region of the fluid bilayer. FTIR
      studies of the Cz=O stretching band indicated that incorporation of FP31 into
      phosphatidylcholine membranes produced a strong dehydration of the polar part of
      the bilayer. In mixtures with L-alpha-dielaidoylphosphatidylethanolamine (DEPE),
      increasing FP31 concentrations broadened and shifted to lower temperatures the
      lamellar to hexagonal-HII phase transition, indicating that this peptide
      destabilized the bilayer and promoted formation of the hexagonal-HII phase. The
      results are discussed in terms of lipid-peptide hydrophobic mismatch and its
      influence on the role of the N-terminal polypeptide of CDV F1 protein in viral
      membrane fusion.

PMID- 14643934
TI  - Characterisation of subunit III and its oligomer from spinach chloroplast ATP
      synthase.
AB  - Proton ATP synthases carry out energy conversion in mitochondria, chloroplasts,
      and bacteria. A key element of the membrane integral motor CFO in chloroplasts is
      the oligomer of subunit III: it converts the energy of a transmembrane
      electrochemical proton gradient into rotational movement. To enlighten prominent
      features of the structure-function relationship of subunit III from spinach
      chloroplasts, new isolation methods were established to obtain highly pure
      monomeric and oligomeric subunit III in milligram quantities. By Fourier
      transform infrared (FTIR) and CD spectroscopy, the predominantly alpha-helical
      secondary structure of subunit III was demonstrated. For monomeric subunit III, a
      conformational change was observed when diluting the SDS-solubilized protein.
      Under the same conditions the conformation of the oligomer III did not change. A
      mass of 8003 Da for the monomeric subunit III was determined by MALDI mass
      spectrometry (MALDI-MS), showing that no posttranslational modifications
      occurred. By ionisation during MALDI-MS, the noncovalent homooligomer III14
      disaggregated into its III monomers.

PMID- 14643935
TI  - Fluorescence properties of Laurdan in cochleate phases.
AB  - Cochleates are lipid-based delivery system that have found application in drug
      and gene delivery. They are precipitates, formed as a result of interaction
      between cations (e.g. Ca2+) and negatively charged phospholipids such as
      phosphatidylserine (PS). In the present study, we investigated the utility of
      fluorescent probe Laurdan (6-dodecanoyl-2-dimethylamino naphthalene) to monitor
      cochleate phase formation. Following addition of Ca2+ to Laurdan labeled lipid
      vesicles comprised of brain phosphatidylserine (BPS), a significant blue shift in
      the emission peak maximum of Laurdan was observed and the spectral features were
      distinct from those observed for the gel and liquid-crystalline (LC) phases. This
      is consistent with the formation of anhydrous cochleate cylinders that was
      further confirmed by electron microscopy studies. Due to dipolar relaxation,
      excitation and emission generalized polarization (GPEx and GPEm) indicate
      transition from a LC to a rigid and dehydrated (RD) cochleate phase. These
      spectral changes were utilized to monitor the influence of lipid composition,
      ionic strength and lamellarity on the formation of cochleate phase. The results
      indicated that the presence of phosphatidylcholine (PC) and bulk Na+
      concentration influenced the formation of cochleate structures from small
      unilamellar vesicles (SUV) and multilamellar vesicles (MLV) composed of PS. The
      presence of PC and higher bulk Na+ concentration stabilized the PS vesicles
      against collapse and total loss of contents, intermediate molecular events in the
      formation of cochleate structures. From these studies, we conclude that Laurdan
      fluorescence is a sensitive and a rapid method to detect cochleate phase
      formation.

PMID- 14643936
TI  - The ion transporter superfamily.
AB  - We define a novel superfamily of secondary carriers specific for cationic and
      anionic compounds, which we have termed the ion transporter (IT) superfamily.
      Twelve recognized and functionally defined families constitute this superfamily.
      We provide statistical sequence analyses demonstrating that these families were
      in fact derived from a common ancestor. Further, we characterize the 12 families
      in terms of (1) the known substrates transported, (2) the modes of transport and
      energy coupling mechanisms used, (3) the family sizes (in numbers of sequenced
      protein members in the current NCBI database), (4) the organismal distributions
      of the members of each family, (5) the size ranges of the constituent proteins,
      (6) the predicted topologies of these proteins, and (7) the occurrence of non
      homologous auxiliary proteins that may either facilitate or be required for
      transport. No member of the superfamily is known to function in a capacity other
      than transport. Proteins in several of the constituent families are shown to have
      arisen by tandem intragenic duplication events, but topological variation has
      resulted from a variety of dissimilar genetic fusion, splicing and insertional
      events. The evolutionary relationships between the members of each family are
      defined, leading to predictions of functionally relevant orthologous
      relationships. Some but not all of the families include functionally dissimilar
      paralogues that arose by early extragenic duplication events.

PMID- 14643937
TI  - Telephone versus in-person interviews for alcohol use: results of the 2000
      National Alcohol Survey.
AB  - This study assesses differences in reports of alcohol use and alcohol-related
      harms using telephone and in-person interviews in a subsample of the 2000
      National Alcohol Survey (NAS) (N = 411). Respondents were given a brief telephone
      interview which assessed their alcohol use and alcohol-related harms in the last
      12 months followed by an in-person interview 2 months later that obtained the
      same data. Approximately 90% (n = 371) reported their drinking status
      consistently between interviews (277 current drinkers; 94 non-drinkers).
      Approximately 7% (n = 29) became current drinkers and 2.7% (n = 11) became non
      drinkers at the second interview. The majority of respondents who changed their
      drinking status in either direction were low level drinkers. Using logistic
      regression modeling, no significant associations were found between demographic
      factors and consistency of reported drinking status. Further, there were no
      differences by mode for the two alcohol consumption measures (mean daily volume
      and mean number of days drank five or more drinks in the last 12 months) and
      alcohol-related harms in the last 12 months for current drinkers (n = 277). In
      conjunction with other mode studies, these findings support the use of telephone
      interviewing in large national surveys to obtain alcohol use and alcohol-related
      harms data.

PMID- 14643938
TI  - Effects of identification and usefulness of the Lie Scale of the Drug Use
      Screening Inventory (DUSI-R) in the assessment of adolescent drug use.
AB  - OBJECTIVES: The main objectives of this study were to evaluate the effects of
      subject identification versus anonymity on adolescents' drug use assessment using
      the Drug Use Screening Inventory-R and to assess the usefulness of the "Lie
      Scale" of that instrument. METHODS: Six hundred and fifty-five Brazilian students
      (5th to 11th graders) from a public school of Sao Paulo participated in the
      study. One third of them were instructed to put their names on the questionnaire,
      one third answered it anonymously and the remaining ones were partially
      identified according to a code list that was kept by one student who represented
      his classmates. The answers of the identified groups of students were compared
      with those from the anonymous group. According to their scores in the Lie Scale,
      the students were divided into two groups: low and high score groups. RESULTS AND
      CONCLUSIONS: No significant differences were found among anonymous, identified
      and partially identified groups regarding alcohol or drug consumption report, or
      in the density of problems in all drug use screening inventory (DUSI) areas.
      Regarding the Lie Scale, the high score group reported lower alcohol or drug
      consumption and fewer alcohol or drug related problems in all DUSI areas when
      compared to the low score group. The results suggest that identification or
      anonymity does not affect the students' answers to the DUSI and point out the
      usefulness of the Lie Scale of DUSI-R.

PMID- 14643939
TI  - Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based
      morphometry study.
AB  - The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts
      its actions in part via blockade of serotonin and dopamine reuptake. Many animal
      and human studies have demonstrated long-lasting reductions in measures of
      central nervous system (CNS) serotonin function following MDMA administration.
      One emerging role of serotonin function in the CNS is a positive trophic effect
      via stimulation of intracellular signaling pathways and trophic factors. We
      hypothesized that human MDMA users might display neocortical gray matter
      reductions due to loss of serotonergically mediated trophic effects on cortical
      cells. However, unlike animal models, most human MDMA users worldwide are
      polydrug users, thereby complicating the assessment of MDMA toxicity in this
      group. Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug
      users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM)
      to assess regional brain gray and white matter concentration. VBM employs
      gray/white matter segmentation and statistical parametric mapping (SPM) analysis
      to calculate a voxel-wise comparison of regional gray or white matter
      concentration. Using this method, we consistently found several brain regions
      having decreased gray matter concentration in MDMA polydrug users. These regions
      were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and
      left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall,
      these preliminary findings suggest that MDMA polydrug users have multiple regions
      of gray matter reduction, potentially accounting for previously reported
      neuropsychiatric impairments in MDMA users. Additional animal model and human
      studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed
      to further explain these findings. Potential explanations for our results
      including pre-existing brain differences predisposing to MDMA polydrug use,
      direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug
      toxicity, or combinations of all these factors.

PMID- 14643940
TI  - Examining mechanisms of action in 12-Step community outpatient treatment.
AB  - Twelve-step theory hypothesizes that changes in specific cognitions and
      behaviors, including adoption of disease model beliefs and involvement in self
      help programs, lead to symptom reduction. We examined the role of self-help
      affiliation in treatment outcome using causal chain analysis. Baseline, end
      treatment and follow-up self-help affiliation and substance use were assessed in
      252 drug and alcohol abusers attending a community program. Participants were
      randomly assigned to one of three cognitive-behavioral or 12-Step oriented
      individual counseling conditions. Participants also were assigned, based on
      problem severity, to one of three treatment settings (partial hospitalization;
      intensive outpatient; standard outpatient) that varied according to intensity of
      additional 12-Step programming. Repeated-measures ANOVA indicated that self-help
      affiliation increased overall during treatment, particularly in the 12-Step
      counseling condition (versus cognitive-behavioral), and the partial
      hospitalization setting (versus standard outpatient). Multiple regression
      indicated that self-help affiliation was negatively associated with substance use
      6 months post-treatment, and that this was not moderated by condition. Self-help
      affiliation predicted outcome most strongly in the partial hospitalization
      setting and not at all in outpatient; however, this effect was accounted for by
      participants' initial problem severity: high-severity patients had poorer
      outcomes if they failed to increase self-help affiliation, relative to those who
      increased affiliation and to low-severity patients regardless of affiliation.
      Results indicate that, in this community-based program, self-help affiliation
      increased as a function of exposure to 12-Step oriented treatment programming,
      and significantly predicted better outcome among patients with high levels of
      problem severity. Implications for future treatment process and dissemination
      research are discussed.

PMID- 14643941
TI  - Smoking status and substance abuse severity in a residential treatment sample.
AB  - Treatment seeking substance abusers were classified as current smokers or non
      smokers to identify differences between groups on psychiatric and substance use
      severity variables. The Addiction Severity Index (fifth edition; ASI) was
      administered to 313 substance abusers seeking treatment in a private, residential
      addictions treatment program. Since current smokers were younger and less
      educated than non-smokers, these variables were entered as covariates in all
      analyses. As measured by the ASI, current smokers experienced a significantly
      greater number of days with drug problems in the last 30 days and were seen as
      being in significantly more need of drug treatment and alcohol treatment by ASI
      interviewers. These findings indicate that smoking status may be a marker for
      greater substance use severity, although the fact that participants were not
      randomly assigned to groups precludes making causal interpretations of these
      data. Areas of future research are suggested including examining the potential
      mediating role of third variables such as personality and temperament.

PMID- 14643942
TI  - Gender comparisons of drug abuse treatment outcomes and predictors.
AB  - Gender differences in drug treatment outcomes and predictors were examined among
      a sample of 511 patients recruited from drug treatment programs across Los
      Angeles County. Face-to-face interviews were conducted at baseline and at 1-year
      follow-up. Results showed that women and men started their drug use and treatment
      careers at similar ages, but men reported greater drug use and criminal
      involvement at baseline. There were no significant differences by gender in drug
      use and alcohol use at follow-up but men reported more crimes than women.
      Separate logistic regression analyses showed that for both women and men, longer
      treatment retention was associated with drug abstinence and crime desistence at
      follow-up. Additional baseline predictors of abstinence at follow-up included use
      of multiple drugs and readiness for treatment for women, and spousal drug use for
      men. For crime desistence, significant predictors include legal involvement and
      treatment readiness for women, and legal involvement, use of multiple drugs, and
      living with children for men. For both women and men, participation in 12-step
      groups and no spousal drug use during follow-up were related to abstinence. There
      were both similarities and differences in predictors of treatment outcome for
      women and men.

PMID- 14643943
TI  - Is oral fluid analysis as accurate as urinalysis in detecting drug use in a
      treatment setting?
AB  - BACKGROUND: Technology for testing oral fluid (OF) for the presence of drugs is
      available for treatment services and is more attractive than urinalysis: its
      validity is not well established. AIMS: Compare the accuracy of methods of on
      site testing of OF and urine. DESIGN: Comparison of the sensitivity and
      specificity of on-site testing of samples of OF and urine collected on the same
      occasion, using subsequent blind laboratory analysis of the same urine samples as
      the standard. SETTING: British addiction treatment service. PARTICIPANTS: 157
      drug dependent persons, 89% with evidence of opiates, 73% male, and 85% aged
      between 20 and 35 years. MEASUREMENTS: Assessment of presence of four drugs using
      SYVA ETS urinalysis and Cozart Rapiscan OF Drug Test systems. Laboratory
      urinalysis using microplate enzyme-immunoassay technique. RESULTS: The
      sensitivity of OF tests and urinalysis were, respectively, for opiates 91 and
      91%, methadone 91 and 94%, and benzodiazepines 6 and 72%. The specificity of OF
      tests and urinalysis were, respectively, for opiates 78 and 67%, methadone 90 and
      95%, and benzodiazepines 95 and 96%. Amphetamine usage was rare. CONCLUSIONS: OF
      testing is as accurate as urinalysis in detecting the presence of opiates and
      methadone, and the absence of methadone and benzodiazepines.

PMID- 14643944
TI  - The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine,
      alone and in combination with alcohol, on simulated driving.
AB  - While methadone is currently the primary pharmacotherapy used in the treatment of
      heroin dependence in Australia, levo-alpha-acetyl-methodol (LAAM) and
      buprenorphine are new pharmacotherapies that are being examined as alternatives
      to methadone maintenance treatment. The aim of this research is to consider the
      effects of the methadone, buprenorphine and LAAM, as used in maintenance
      pharmacotherapy for heroin dependence, upon simulated driving. Clients stabilised
      in methadone, LAAM and buprenorphine treatment programs for 3 months, and a
      control group of non-drug-using participants, took part in this study which
      involved operating a driving simulator over a 75 min period. All participants
      attended one session without alcohol and one session with alcohol at around the
      0.05% blood alcohol level. Simulated driving skill was measured through standard
      deviations of lateral position, speed and steering wheel angle, and reaction time
      to a subsidiary task was also measured. While alcohol impaired all measures of
      driving performance, there were no differences in driving skills across the four
      participant groups. These findings suggest that typical community standards
      around driving safety should be applied to clients stabilised in methadone, LAAM
      and buprenorphine treatment. The findings are important in terms of the
      widespread implementation of these treatment options in Victoria given that a
      large proportion of pharmacotherapy clients drive.

PMID- 14643945
TI  - Brief measures of sensation seeking for screening and large-scale surveys.
AB  - Sensation seeking is central to research on the prevention of risky health
      behaviors, but current measures of sensation seeking are fairly long, thereby
      reducing their chances of inclusion in some research projects. Hence, we
      developed and evaluated two brief indices of sensation seeking, a four-item
      measure that retains the framework of the Sensation Seeking Scale-Form V (SSS-V)
      and a shorter two-item measure focusing on the risk-taking elements of sensation
      seeking. We compared the performance of the new indices with that of two well
      documented but longer measures of sensation seeking. The evaluation was based on
      data provided by more than 5000 teens and pre-teens in grades 7 through 11.
      Psychometric analyses revealed that the internal consistency of the two new
      measures was very good overall and across grade and sex categories. Additionally,
      the new indices correlated as expected with a series of risk and protective
      factors as well as tobacco, alcohol, and marijuana use. Both indices performed in
      ways remarkably similar to the established measures of sensation seeking and
      should prove useful for future research involving risky health behaviors.

PMID- 14643946
TI  - Comprehensive deficits in performance of an attentional task produced by co
      administering alcohol and nicotine to rats.
AB  - BACKGROUND: Nicotine can improve and alcohol can impair attentional performance
      in rats, but little is known about the effects of mixtures of the two drugs with
      respect to attention. AIMS: The aims were to investigate the effects of alcohol
      and nicotine alone and when co-administered on performance of a five-choice
      serial reaction time task, and to examine the impact of task difficulty by
      varying durations of the limited hold (LH) for availability of the reinforcer.
      METHODS: Male hooded rats were trained to respond (nose-poke) to a 0.5 s light
      stimulus presented randomly in one of five apertures to obtain food reinforcers.
      Three groups of rats trained with different LH values were used (n = 10).
      RESULTS: The first experiment showed that training at different LH values had
      little effect on performance when the LH value during testing was held constant.
      Experiment 2 showed that alcohol (0.4-1.6 g/kg, i.p.) had no effect on the
      percentage of correct responses (accuracy) but it impaired all speed-related
      indices. In the third experiment, the effects of nicotine (0.1 and 0.2 mg/kg,
      s.c.) were determined alone and on the dose-response curve for alcohol (0.4-1.2
      g/kg, i.p.). Nicotine alone produced small improvements in performance whereas co
      administration of nicotine and alcohol produced large decrements at doses of
      alcohol that themselves only slightly impaired performance. These decrements
      included impairments of accuracy as well as of anticipatory responding, omission
      errors, response latencies and reinforcers earned. There were no marked or
      consistent interactions of drug effects with LH values. CONCLUSIONS: Task
      performance was disrupted to a much greater extent by co-administration of
      alcohol and nicotine than by alcohol alone; therefore, it seems unlikely that an
      ability of nicotine to reverse the effects of alcohol can account for
      associations between the use of the two substances.

PMID- 14643947
TI  - Opiate maintenance with buprenorphine in ambulatory care: a 24-week follow-up
      study of new users.
AB  - BACKGROUND: Many studies suggest that buprenorphine, a long acting partial opioid
      agonist, may be comparable to methadone in efficacy, with fewer withdrawal
      symptoms and a lower risk of overdose. The aim of this study was to assess the
      patterns of buprenorphine prescription use in ambulatory care and retention rate
      under treatment during a 24-week follow-up period. METHODS: This observational
      cohort study included buprenorphine users identified from the French Health
      System prescription database in an area of 1 million inhabitants and followed for
      24 weeks. RESULTS: We selected 282 users of buprenorphine defined as "new users"
      (74% male, mean age 32.4+/-6.2 years). Three groups were defined: 50% of
      "rational users" (141 subjects, no more than 2 prescribers), 24% of "occasional
      users" (67 subjects, less than 2 buprenorphine prescriptions) and 26% of "non
      rational users" (74 subjects, 3 or more prescribers). The overall 24-week
      treatment retention rate was 37%. Misuse of buprenorphine or benzodiazepines was
      significantly more frequent in "non-rational" than "rational users". CONCLUSION:
      The retention rate with buprenorphine estimated in this observational study was
      very similar to that obtained in controlled trials. A majority of regular users
      of buprenorphine could be regarded as "rational users" in this area of France.

PMID- 14643948
TI  - Towards genetic prediction of radiation responses: ESTRO's GENEPI project.

PMID- 14643949
TI  - Prediction of normal tissue radiosensitivity from polymorphisms in candidate
      genes.
AB  - BACKGROUND AND PURPOSE: Single nucleotide polymorphisms (SNPs) in genes related
      to the biological response to radiation injury may affect clinical normal tissue
      radiosensitivity. This study investigates whether seven selected SNPs in five
      candidate genes influence risk of subcutaneous fibrosis and telangiectasia after
      radiotherapy. PATIENTS AND METHODS: The 41 patients included in this study were
      given post-mastectomy radiotherapy in 1978-1982 and subsequently evaluated in
      detail with regard to several different normal tissue reactions. SNPs in TGFB1
      (codons 10, 25 and position -509), SOD2 (codon 16), XRCC3 (codon 241), XRCC1
      (codon 399) and APEX (codon 148) were analyzed by PCR and single nucleotide
      primer extension. Dose-response curves were established for subcutaneous fibrosis
      and telangiectasia in patients with different genotypes. Differences in
      radiosensitivity were quantified in terms of ED(50) values and enhancement
      ratios. RESULTS: For TGFB1, the Pro/Pro genotype in codon 10 and the T/T genotype
      in position -509 correlated positively with risk of subcutaneous fibrosis. The
      SOD 2 codon 16 Val/Ala genotype was associated with increased risk of
      subcutaneous fibrosis when compared to the Val/Val genotype. The Thr/Thr genotype
      in XRCC3 codon 241 correlated with increased risk of subcutaneous fibrosis as
      well as telangiectasia. The Arg/Arg genotype in XRCC1 codon 399 was associated
      with increased risk of radiation-induced subcutaneous fibrosis. For these
      polymorphisms, enhancement ratios between 1.09 and 1.25 were found. Combined
      analysis of multiple SNPs demonstrated that the risk of subcutaneous fibrosis
      correlated with the number of risk alleles in such a manner that patients with
      few risk alleles exhibited a remarkable degree of radioresistance. CONCLUSION:
      The present study established significant correlations between five SNPs and risk
      of radiation-induced normal tissue reactions. These findings support the
      assumption that clinical normal tissue radiosensitivity should be regarded as a
      phenomenon dependent on the combined effect of variation in several genes and
      indicate that models based on multiple genetic markers may have the potential to
      predict normal tissue responses after radiotherapy.

PMID- 14643950
TI  - Individual radiosensitivity measured with lymphocytes may be used to predict the
      risk of fibrosis after radiotherapy for breast cancer.
AB  - BACKGROUND AND PURPOSE: To analyse the relationship of individual cellular
      radiosensitivity and fibrosis after breast conserving therapy. A new model was
      used describing the percentage of patients developing fibrosis per year and per
      patient at risk. PATIENTS AND METHODS: In a retrospective study, 86 patients were
      included, who had undergone breast conserving surgery and irradiation of the
      breast with a median dose of 55 Gy (54-55 Gy) given at 2.5 Gy/fraction (n=57) or
      2 Gy/fraction (n=29). Median age was 62 years (range 44-86) and median follow-up
      was 7.5 years (range 5-17). Patients were examined for fibrosis according to the
      LENT/SOMA score. For analysis, fibrosis was classified as grade 0 and grade 1 (G0
      1) or present grade 2 and grade 3 (G2-3). The time to complete development of
      fibrosis was determined by analysis of yearly mammograms. Individual cellular
      radiosensitivity was determined by scoring lethal chromosomal aberrations in in
      vitro irradiated (6 Gy) lymphocytes using metaphase technique. Patients with
      low/intermediate cellular radiosensitivity were compared with patients with high
      cellular radiosensitivity using actuarial methods. RESULTS: Ten patients
      developed fibrosis at 1-8 years after radiotherapy. Individual cellular
      radiosensitivity was described by normal distribution of lethal chromosomal
      aberrations, the average was 5.47 lethal aberrations per cell (standard deviation
      (SD) 0.71). Cellular radiosensitivity was defined as low/intermediate (< or =6.18
      lethal aberrations) in 73 patients and high (>6.18 lethal aberrations; mean+SD)
      in 13 patients. In both groups, the actuarial rate of fibrosis-free patients
      decreased exponentially with time after radiotherapy. Patients with high cellular
      radiosensitivity showed a 2.3-fold higher annual rate for fibrosis than patients
      with intermediate and low radiosensitivity (3.6 versus 1.6% per year).
      CONCLUSIONS: In breast cancer patients, high individual cellular radiosensitivity
      as determined by the number of lethal chromosome aberrations in in vitro
      irradiated lymphocytes might be associated with an enhanced annual rate of
      fibrosis.

PMID- 14643951
TI  - Personal characteristics, therapy modalities and individual DNA repair capacity
      as predictive factors of acute skin toxicity in an unselected cohort of breast
      cancer patients receiving radiotherapy.
AB  - BACKGROUND AND PURPOSE: Intrinsic and extrinsic factors can affect the occurrence
      of side effects of radiotherapy. The influence of therapy modalities, personal
      characteristics and individual DNA repair capacity on the risk of acute skin
      toxicity was thus evaluated. MATERIALS AND METHODS: In a prospective study of 478
      female breast cancer patients receiving adjuvant radiotherapy of the breast after
      breast-conserving surgery, acute skin toxicity was documented systematically
      using a modified version of the common toxicity criteria. Prognostic personal and
      treatment characteristics were identified for the entire cohort. Individual DNA
      repair capacity was determined in a subgroup of 113 patients with alkaline comet
      assay using phytohemagglutinin stimulated lymphocytes. Using proportional hazards
      analysis to account for cumulative biologically effective radiation dose, the
      hazard for the development of acute skin reactions (moist desquamation)
      associated with DNA repair capacity was modeled. RESULTS: Of the 478
      participants, 84 presented with acute reactions by the end of treatment. Higher
      body mass index was significantly associated with an increased risk for acute
      reactions (hazard ratio=1.09 per 1 kg/m(2)), adjusted for treating hospital and
      photon beam quality. The comet assay parameters examined, including background
      DNA damage in non-irradiated cells, DNA damage induced by 5 Gy, and DNA repair
      capacity, were not significantly associated with risk of acute skin toxicity.
      CONCLUSIONS: Higher BMI is predictive of acute skin toxicity, however, individual
      repair parameters as determined by the alkaline comet assay are not informative
      enough. More comprehensive analyses including late effects of radiotherapy and
      repair kinetics optimized for different radiation-induced DNA lesions are
      warranted.

PMID- 14643952
TI  - Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene
      mutations: no observation of increased radiation-induced acute or late effects.
AB  - BACKGROUND AND PURPOSE: Reports on increased late subcutaneous toxicity after
      radiation therapy (RT) in breast cancer patients carrying ATM gene mutations has
      raised concerns about RT as part of the management in these patients. The impact
      of ataxia-telangiectasia (A-T) heterozygosity on clinical radiosensitivity
      remains a matter of debate while clinical data are scarce. PATIENTS AND METHODS:
      Between September 1995 and December 2002 genomic DNA samples were collected from
      1100 unselected breast cancer patients receiving adjuvant radiotherapy at our
      department. Using mutation-specific assays, we screened for frequent ATM gene
      mutations. Analysis of acute and late radiation-related toxicity for skin and
      subcutaneous normal tissue was performed in patients identified as A-T
      heterozygotes applying common toxicity criteria (CTC) and LENT/SOMA (late effects
      on normal tissue/subjective objective management analytic) scoring criteria,
      respectively. RESULTS: Eleven patients were identified to be heterozygous for a
      pathogenic ATM gene mutation. Ten patients had received at least one course of
      RT. Median follow-up after completion of radiotherapy was 5.1 years (range 1.7
      7.2). There was no evidence of increased radiation-induced acute or late skin or
      subcutaneous reactions in patients treated with linac-based RT. One patient
      failed distantly and was subsequently irradiated at four different sites for bone
      and brain metastases. Local relapse occurred in the single patient who had
      declined adjuvant RT following breast conservative therapy. CONCLUSIONS: Our
      results do not provide evidence for a relative contraindication to adjuvant RT in
      A-T heterozygous breast cancer patients. Due to their increased cellular
      radiosensitivity, these patients may differentially benefit from RT and qualify
      for dose and volume reduction trials.

PMID- 14643953
TI  - Acute radiation reactions in oral and pharyngeal mucosa: tolerable levels in
      altered fractionation schedules.
AB  - PURPOSE: To investigate whether a predictive estimate can be obtained for a
      'tolerance level' of acute oral and pharyngeal mucosal reactions in patients
      receiving head and neck radiotherapy, using an objective set of dose and time
      data. MATERIALS AND METHODS: Several dozen radiotherapy schedules for treating
      head and neck cancer have been reviewed, together with published estimates of
      whether they were tolerated or (in a number of schedules) not. Those closest to
      the borderline were given detailed analysis. Total doses and biologically
      effective doses (BED or ERD) were calculated for a range of starting times of
      cellular repopulation and rates of daily proliferation. Starting times of
      proliferation from 5 to 10 days and daily cellular doubling rates of 1-3 days
      were considered. The standard published form of BED with its linear overall time
      factor was used: BED=nd(1 + d/(alpha/beta) - Ln2(T - T(k))/alpha T(p) (see text
      for parameters). RESULTS: A clear progression from acceptable to intolerable
      mucosal reactions was found, which correlated with total biologically effective
      dose (BED in our published modeling), for all the head and neck cancer
      radiotherapy schedules available for study, when ranked into categories of
      'intolerable' or 'tolerable'. A review of published mechanisms for mucosal
      reactions suggested that practical schedules used for treatment caused stimulated
      compensatory proliferation to start at about 7 days. The starting time of
      compensatory proliferation had little predictive value in our listing, so we
      chose the starting time of 7 days. Very short and very long daily doubling rates
      also had little reliability, so we suggest choosing a doubling time of 2.5 days
      as a datum. With these parameters a 'tolerance zone of uncertainty' could be
      identified which predicted acute-reaction acceptability or not of a schedule
      within a range of about 2-10 Gy in total BED. If concurrent chemoradiotherapy is
      used, our provisional suggestion is that this zone should be reduced by up to
      roughly 3-5 Gy10 in BED, with a request for further evidence. CONCLUSIONS: It is
      suggested that total BED should be used, as specified above. Parameters of
      alpha=0.35 Gy-(1), alpha/beta=10 Gy, Tk=7 days and Tp=2.5 days are suggested. The
      'acute/ tolerance zone' then turns out to be 59-61 Gy10 for radiation-only
      treatments. Further information about the decrement caused by concurrent head-and
      neck cancer chemoradiotherapy, possibly 3-5 Gy10, is required.

PMID- 14643954
TI  - Radiological and clinical assessment of long-term brain tumour survivors after
      radiotherapy.
AB  - BACKGROUND AND PURPOSE: Late adverse effects of therapeutic brain radiotherapy
      (RT) may develop after long latency periods and our objective was to assess long
      term brain tumour survivors following RT to large partial brain volumes.
      MATERIALS AND METHODS: Assessment of MRI, SOMA/LENT score, quality of life and
      neuroendocrine function was performed in 33 adult brain tumour patients 6-25
      years following RT. Fraction dose was 1.8 Gy to a median total dose of 54 Gy
      (range: 45.0-59.4 Gy). Ten patients had been given two opposing portals including
      one whole hemisphere, while 23 patients had in addition received an ipsilateral
      field. In 25 patients the hypothalamic and pituitary area had been included in
      the RT field. Results were compared within the study group and towards the
      general population matched for age and gender. RESULTS: All patients had white
      matter changes with increased signal intensity on T2 and FLAIR images. Discrete
      lesions (grade 1), beginning confluence of lesions (grade 2), and large confluent
      areas (grade 3) were present in 8, 8 and 17 patients, respectively. Patients
      treated with intra-arterial chemotherapy and patients at higher age at follow-up
      had significantly more grade 3 changes. Atrophy, lacunar lesions and contrast
      enhancement was found in 17, 18 and 23 patients, respectively. Significantly
      worse clinical status and quality of life was found in patients with white matter
      changes grade 3 or atrophy. Patients given full-dose RT to less volume did not
      have significantly less toxicity. Two cases of meningioma were found at 16 and 22
      years after RT. Nineteen neuroendocrine abnormalities were observed in 16/25
      patients. CONCLUSIONS: External radiotherapy to the brain at a standard
      fractionation regime will cause varying degrees of late neurotoxicity and/or
      neuroendocrine disturbances in most patients. Life-long follow-up is recommended.

PMID- 14643955
TI  - Neuropsychological outcome after fractionated stereotactic radiotherapy (FSRT)
      for base of skull meningiomas: a prospective 1-year follow-up.
AB  - PURPOSE: The purpose of this study was to evaluate the cognitive outcome after
      fractionated stereotactic radiotherapy (FSRT) in patients with base of skull
      meningiomas. METHODS AND MATERIAL: A total of 40 patients with base of skull
      meningiomas were neuropsychologically evaluated before, after the first fraction
      (1.8 Gy), at the end of FSRT (n=37), 6 weeks (n=24), 6 (n=18) and 12 months
      (n=14) after FSRT. A comprehensive test battery including assessment of general
      intelligence, attention and memory functions was used. Alternate forms were used
      and current mood state was controlled. RESULTS: After the first fraction a
      transient decline in memory function and simultaneous improvements in attention
      functions were observed. No cognitive deteriorations were seen during further
      follow-up, but increases in attention and memory functions were observed. Mood
      state improved after the first fraction, at the end of radiotherapy and 6 weeks
      after radiotherapy. CONCLUSION: The present data support the conclusion that the
      probability for the development of permanent cognitive dysfunctions appears to be
      very low after FSRT. The transient memory impairments on day 1 are interpreted as
      most likely related to an increase of a preexisting peritumoral edema, whereas
      the significant acute improvements in attention functions are interpreted as
      practice effects. An analysis of localization specific effects of radiation
      failed to show clear hemisphere specific cognitive changes.

PMID- 14643956
TI  - A method for reducing ovarian doses in whole neuro-axis irradiation for
      medulloblastoma.
AB  - BACKGROUND AND PURPOSE: Cranio-spinal irradiation for medulloblastoma can impair
      fertility in girls. The literature indicates that an ovarian dose of 4 Gy causes
      permanent infertility in 30% of young females and that doses of <1.5 Gy over the
      whole treatment are desirable. We report a modified radiotherapy technique using
      a non-divergent beam edge inferiorly to reduce the ovarian dose. PATIENTS AND
      METHODS: Eight female patients with medulloblastoma had magnetic resonance
      imaging (MRI) studies in the treatment position to identify the position of their
      ovaries relative to the radiation field. The information was transferred to the
      radiotherapy planning system and plans were generated using conventional spinal
      fields and modified fields with a half beam block at the inferior border.
      RESULTS: Identifying the position of the ovaries by MRI enabled the dose to be
      estimated for the two techniques. Using a non-divergent beam inferiorly, the mean
      ovarian dose was reduced in all cases by a median value of 2.45 Gy (range 0.6
      19.5 Gy) and the median percentage reduction was 66.8% (range 2.6-84.6%). The
      position of the ovary relative to the beam edge was critical in determining the
      dose reduction for each case. The modified technique doubled the number of
      patients receiving <4 Gy to a single ovary from three to six. With this
      alteration, three patients also had an ovary receiving <1.5 Gy whereas all
      exceeded this dose with conventional treatment. CONCLUSION: We recommend using
      asymmetry at the inferior spinal border to achieve a non-divergent edge to the
      treatment field to reduce the dose to the ovary. Using MRI to localise the
      ovaries is important in estimating their dose and in assisting the counselling of
      patients and their families about future fertility.

PMID- 14643957
TI  - Quantitative assessment of inter-clinician variability of target volume
      delineation for medulloblastoma: quality assurance for the SIOP PNET 4 trial
      protocol.
AB  - BACKGROUND AND PURPOSE: To assess inter-clinician variability amongst specialist
      paediatric radiation oncologists in delineating clinical target volumes for
      treating medulloblastoma as a quality assurance exercise prior to the
      introduction of the SIOP PNET 4 trial protocol of conformal radiotherapy to the
      posterior fossa and tumour bed. PATIENTS AND METHODS: Participants from 17 UK
      centres attended an educational meeting and then completed a clinical planning
      exercise to outline: (1) the whole posterior fossa and (2) the tumour bed.
      Quantitative analysis of the volumes, lengths, spatial positioning and axial
      planes for each individual was carried out and variation between individuals
      analysed. RESULTS: Outlining of the posterior fossa was reasonably consistent,
      although most variation was seen in defining the superior border of the
      tentorium. A major difference was the decision whether or not to include the post
      surgical meningocoele in the clinical target volume (CTV). The CTV for the tumour
      bed was under treated by all participants due to lack of inclusion of pre
      operative tumour extent. CONCLUSIONS: This exercise demonstrated several
      ambiguities in the draft protocol and highlighted particular areas of inter
      clinician variation. Consequently the protocol was revised and improved to take
      account of these findings. We recommend that planning exercises, in conjunction
      with education and training, should be implemented before the start of any new
      radiotherapy trial. In the future, the use of image transfer will allow
      prospective peer review of target volumes before treatment commences. These
      measures are essential to ensure that alterations in clinical practice are
      achieved in a uniform way.

PMID- 14643958
TI  - Assessment of morbidity in carcinoma of the cervix: a comparison of the LENT SOMA
      scales and the Franco-Italian glossary.
AB  - BACKGROUND AND PURPOSE: To assess the correlation between the LENT (late effects
      on normal tissue) SOMA (subjective objective management analytic) system and the
      Franco-Italian glossary scores of late morbidity in cervical cancer patients
      treated with radiation, and to compare the ability of the scoring systems to
      detect differences between radiation treatment groups. MATERIALS AND METHODS: The
      study was retrospective. Patients, invited to take part in the study, had
      radiotherapy for cervical cancer and had a minimum of 3 years follow-up with no
      evidence of recurrence. One hundred patients agreed to take part. LENT subjective
      data were obtained using a patient questionnaire approach in order to complete
      the scales as published. The LENT objective, management and Franco-Italian
      glossary scores were obtained by a physician. Correlations between scores and
      differences between treatment groups were examined using non-parametric tests.
      RESULTS: The average LENT SOMA scores had a greater resolution than the maximum
      scores, and using the maximum score alone underestimated treatment morbidity. The
      Franco-Italian glossary scores correlated strongly with the LENT objective scores
      (rho=0.61, P<0.0005), and less strongly with the LENT subjective scores
      (rho=0.45, P<0.0005). Significant differences in morbidity between the radiation
      treatment groups were measured using both the LENT SOMA system and the Franco
      Italian glossary. CONCLUSIONS: The maximum and average LENT scores should be
      reported for each subsite. The LENT objective scores correlated well with the
      scores obtained using the established Franco-Italian glossary, but the LENT
      system provided additional information on subjective treatment effects. Both
      systems were able to measure significant differences in morbidity between
      radiation treatment groups. In conclusion, the LENT SOMA system is a valid and
      comprehensive approach for scoring the late normal tissue effects of
      radiotherapy.

PMID- 14643959
TI  - A dosimetric analysis of acute gastrointestinal toxicity in women receiving
      intensity-modulated whole-pelvic radiation therapy.
AB  - PURPOSE: To identify dosimetric factors correlated with acute gastrointestinal
      (GI) toxicity in gynecology patients undergoing intensity-modulated whole pelvic
      radiation therapy (IM-WPRT). MATERIAL AND METHODS: Fifty gynecology patients
      received IM-WPRT (45-1.8Gy/fraction) between 2/00 and 3/02. All patients were
      treated to a clinical target volume (CTV) consisting of the upper vagina,
      parametria, uterus, presacral region and pelvic lymph nodes. Grade 2 acute GI
      toxicity requiring frequent medications and grade 3-5 toxicities were designated
      as clinically significant and analyzed as a function of patient and dosimetric
      variables. The most significant volumetric factors were fit to a normal tissue
      complication probability (NTCP) function. RESULTS: Fourteen women (28%) developed
      clinically significant acute GI toxicity. None of the patient factors were
      correlated with acute GI toxicity. In addition, the volume of rectum receiving
      25, 50, 75, 90, 100 and 110% of the prescription dose did not reach statistical
      significance. In contrast, a correlation was observed between the volume of small
      bowel (SB) irradiated and acute GI toxicity, particularly the SB volumes
      receiving 90 and 100% of the prescription dose (p=0.009 and p=0.009,
      respectively). Controlling for patient and other dosimetric factors, the SB
      volume receiving the 100% (Vol(SB,100)) of the prescription dose remained the
      sole significant factor on multivariate analysis (p=0.012). Subsequently, a NTCP
      curve, quantifying the risk of acute GI toxicity, was generated based on the
      Vol(SB,100). CONCLUSIONS: The most significant factor correlated acute GI
      toxicity in gynecology patients undergoing IM-WPRT is Vol(SB,100).

PMID- 14643960
TI  - Association of anorectal dose-volume histograms and impaired fecal continence
      after 3D conformal radiotherapy for carcinoma of the prostate.
AB  - PURPOSE: The late toxicity of fecal incontinence after pelvic radiotherapy is now
      frequently recognized but the etiology poorly understood. We therefore
      investigated associations between dose-volume histogram (DVH) parameters of the
      rectum and the anal canal with fecal continence as measured by an established 10
      item questionnaire. METHODS AND MATERIALS: Forty-four patients treated for
      carcinoma of the prostate with 58-72 Gy of 3D conformal radiotherapy between 1995
      and 1999 who completed the questionnaire formed the study population. Total
      continence scores of treated patients obtained 1.5 years (median) after
      radiotherapy were compared to a control group of 30 patients before radiotherapy.
      Median, mean, minimum and maximum doses as well as the volume (% and ml) treated
      to 40, 50, 60 and 70 Gy were determined separately for anal canal and rectum. DVH
      parameters were correlated with total continence score (Spearman rank test) and
      patients grouped according to observed continence were compared regarding DVH
      values (Mann-Whitney U-test). RESULTS: Median fecal continence scores were
      significantly worse in the irradiated than in the control group (31 vs. 35 of a
      maximum 36 points). In treated patients, 59%/27%/14% were classified as fully
      continent, slightly incontinent and severely incontinent. Continence was similar
      in the 58-to-62-Gy, 66-Gy and 68-to-72-Gy dose groups. No DVH parameter was
      significantly correlated with total continence score, but severely incontinent
      patients had a significantly higher minimum dose to the anal canal than fully
      continent/slightly incontinent, accompanied by portals extending significantly
      further inferiorly with respect to the ischial tuberosities. CONCLUSIONS:
      Excluding the inferior part of the anal canal from the treated volume in 3D
      conformal therapy for carcinoma of the prostate appears to be a promising
      strategy to prevent radiation-induced fecal incontinence.

PMID- 14643961
TI  - Finding dose-volume constraints to reduce late rectal toxicity following 3D
      conformal radiotherapy (3D-CRT) of prostate cancer.
AB  - BACKGROUND AND PURPOSE: The rectum is known to display a dose-volume effect
      following high-dose 3D-conformal radiotherapy (3D-CRT). The aim of the study is
      to search for significant dose-volume combinations with the specific treatment
      technique and patient set-up currently used in our institution. PATIENTS AND
      METHODS: We retrospectively analyzed the dose-volume histograms (DVH) of 135
      patients with stage T1b-T3b prostate cancer treated consecutively with 3D-CRT
      between 1996 and 2000 to a total dose of 76 Gy. The median follow-up was 28
      months (range 12-62). All late rectal complications were scored using RTOG
      criteria. Time to late toxicity was assessed using the Kaplan-Meyer method. The
      association between variables at baseline and > or=2 rectal toxicity was tested
      using chi(2) test or Fisher's exact test. A multivariate analysis using logistic
      regression was performed. RESULTS: Late rectal toxicity grade > or=2 was observed
      in 24 of the 135 patients (17.8%). A 'grey area' of increased risk has been
      identified. Average DVHs of the bleeding and non-bleeding patients were
      generated. The area under the percent volume DVH for the rectum of the bleeding
      patients was significantly higher than that of patients without late rectal
      toxicity. On multivariate analysis the correlation between the high risk DVHs and
      late rectal bleeding was confirmed. CONCLUSIONS: The present analysis confirms
      the role of the rectal DVH as a tool to discriminate patients undergoing high
      dose 3D-CRT into a low and a high risk of developing late rectal bleeding. Based
      on our own results and taking into account the data published in the literature,
      we have been able to establish new dose-volume constraints for treatment
      planning: if possible, the percentage of rectal volume exposed to 40, 50, 60, 72
      and 76 Gy should be limited to 60, 50, 25, 15 and 5%, respectively.

PMID- 14643962
TI  - 3-Nitrobenzanthrone (3-NBA) induced micronucleus formation and DNA damage in
      human hepatoma (HepG2) cells.
AB  - 3-Nitrobenzanthrone (3-NBA), identified in diesel exhaust and in airborne
      particulate matter, is a potent mutagen in Salmonella, induces micronuclei
      formation in mice and in human cells and DNA adducts in rats. In the present
      study, we investigated the genotoxic potency of 3-NBA in human HepG2 cells using
      the micronucleus (MN) assay and the single cell gel electrophoresis (SCGE). 3-NBA
      caused a genotoxic effect at concentrations > or =12 nM in both assays. In the
      micronucleus assay, we found 98.7+/-10.3 MN/1000 BNC at a concentration of 100 nM
      3-NBA in comparison to 27.3+/-0.6 MN/1000 BNC with the negative control. At the
      same concentration, the DNA-migration (SCGE) showed an Olive tail moment (OTM) of
      2.7+/-0.45 and %DNA in the tail of 8.28+/-0.76; OTM and %DNA in the tail of cells
      treated with the negative control were 0.73+/-0.08 and 2.81+/-0.30, respectively.
      The results are discussed under consideration of former studies.

PMID- 14643963
TI  - Comparative study of the uterotrophic potency of 14 chemicals in a uterotrophic
      assay and their receptor-binding affinity.
AB  - We performed an immature rat uterotrophic assay of 14 chemicals having various
      receptor-binding affinities in order to assess the relationship between their
      uterotrophic potency and receptor-binding affinity. The chemicals tested were
      phthalic acid di-n-hexyl ester, phthalic acid di-n-amyl ester, phthalic acid di-n
      propyl ester, 2-ethylhexyl-p-hydroxybenzoate, 4,4'-biphenol, 4,4'
      sulfonyldiphenol, 4,4'-dihydroxydiphenylmethane, 2,4-dihydroxybenzophenone, 4,4'
      cyclohexylidenebisphenol, 4-t-butylpyrocatechol, clomiphene citrate, 4,4'-(1,3
      phenylenediisopropylidene)bisphenol, p-t-butylphenol, and diallylterephthlate.
      Two of the 14 chemicals, phthalic acid di-n-propyl ester and diallylterephthlate,
      exhibited no receptor-binding affinity, and the receptor-binding affinity of
      phthalic acid di-n-hexyl ester and phthalic acid di-n-amyl ester was lower than
      that of the other chemicals. Ten of the chemicals showed uterotrophic potency,
      the exceptions being phthalic acid di-n-propyl ester, diallylterephthlate,
      phthalic acid di-n-hexyl ester, and phthalic acid di-n-amyl ester. The results of
      the present study demonstrate that the affinity of the chemicals in the receptor
      binding assay correlated well with their potency in the uterotrophic assay except
      for a few chemicals with very low receptor-binding affinity.

PMID- 14643964
TI  - Reproductive adverse effects of fipronil in Wistar rats.
AB  - The purpose of the present study was to investigate possible reproductive adverse
      effects of fipronil (Frontline TopSpot) in female Wistar rats. The pesticide was
      topically applied to rats (single dose) at different concentrations (70, 140 and
      280 mg/kg) and hormonal analysis, estrous cycle, and pregnancy and outcome data
      were determined. Treatment with fipronil altered cyclicity of female rats
      lengthening the estrous cycle (days) after a single topic administration of 70
      mg/kg (9.7+/-1.18) or 280 mg/kg (14.5+/-1.45) when compared to control (4.8+/
      0.17). In the mating study fipronil reduced the pregnancy index (67%) in the
      highest dose group (280 mg/kg). Plasma progesterone and estradiol levels,
      obtained in different periods after treatment with fipronil (70 mg/kg), were
      significantly different 96 h after treatment, when compared to controls. In
      summary, the results of the present study indicate that fipronil may alter the
      normal functioning of the endocrine system and cause adverse reproductive effects
      in female rats.

PMID- 14643965
TI  - Micronuclei induction by 13 week-inhalation of 1,1-dichloro-1-fluoroethane in
      Sprague-Dawley rats.
AB  - To investigate the genotoxic effect of l,1-dichloro-1-fluoroethane (HCFC-141b),
      which was currently widely used as a cleaning solvent in the electronic parts
      industry and suggested as a potential reproductive effector, in vivo micronucleus
      tests were performed. Groups of 10 male and 10 female Sprague-Dawley rats were
      exposed, by inhalation (6h/day, 5 days/week) to the vapors of HCFC-141b for 13
      weeks using whole body exposure chambers at the concentrations of 0 (control),
      1500, 3000, and 6000 ppm. The micronuclei frequencies among the polychromatic
      erythrocytes (PCEs) and the percentage of polychromatic erythrocytes among the
      total number of erythrocytes were counted in the bone marrow of rats, and body
      weights, organ weights, histopathology, clinical chemistry and hematologic
      changes were also observed. Statistically significant and dose-dependant
      increases were found in the micronuclei frequencies in the male rats (P<0.01),
      yet not in the females. The decreases in the percentage of polychromatic
      erythrocytes among the total number of erythrocytes were also statistically
      significant (P<0.05) in both sexes of the high concentration groups. However, no
      exposure-related effects of toxicological significance were noted with respect to
      organ weights, clinical chemistry and histopathology. Apart from it, only
      slightly decreased mean corpuscular hemoglobin concentration (MCHC) was noted in
      the females of 6000 ppm group (P<0.05). These results suggest that HCFC 141b can
      induce the genetic effects, micronuclei in the rat bone marrows, especially in
      males, at earlier stages before the other general clinical and histopathologic
      changes occur if with more prolonged exposure.

PMID- 14643966
TI  - The induction of amyloid precursor protein and alpha-synuclein in rat hippocampal
      astrocytes by diethyldithiocarbamate and copper with or without glutathione.
AB  - alpha-Synuclein is the major component of Lewy bodies. Its aggregation can be
      accelerated by copper, iron, or beta-amyloid (Abeta) and has been thought to
      provide a nucleation center during the formation of amyloid plaques. The main
      structural component of amyloid plaque is Abeta, which is derived from a larger
      protein, amyloid precursor protein (APP). Xenobiotics have been implicated in the
      etiology of the neurodegenerative disease. Mechanisms of diethyldithiocarbamate
      (DDC) neurotoxicity involve copper chelation and interactions with SH groups
      resulting in oxidative stress. In this study, rat hippocampal astrocytes were
      treated with DDC (75 microM), CuCl(2) (0.2 microM), or DDC (75 microM) plus
      CuCl(2) (0.2 microM) for 1h. Cells were allowed to recover with or without 10 mM
      GSH. Results showed an increase of APP and alpha-synuclein production occurring
      in a time-dependent manner. At 4 h post-treatment, cells contained small
      positively stained material deposited throughout the cytosol for APP and by 8 h
      post-treatment increases were seen in both APP and alpha-synuclein. Immunoblots
      supported immunocytochemical results. Glutathione (GSH) decreased the
      accumulation of these proteins at 8 h post-treatment.

PMID- 14643967
TI  - Sensitivity of the FPG protein towards alkylation damage in the comet assay.
AB  - The comet assay (single cell gel electrophoresis) is widely used for the
      evaluation of DNA-damaging effects in genotoxicity testing and population
      monitoring. In its standard version at pH >13, DNA double strand breaks (DSB),
      DNA single strand breaks (SSB) and alkali-labile sites (ALS) lead to increased
      DNA migration. At reduced pH (12.5-12.1) the expression of ALS as SSB can be
      eliminated and the effect of SSB only can be identified. Specific endonucleases
      have been used to characterize specific classes of DNA damage. The formamido
      pyrimidine glycosylase (FPG) protein has been used to assess oxidative DNA base
      damage because it detects 8-OH guanine and other oxidatively damaged purines.
      Here, we show that the FPG protein also detects alkylation damage with high
      sensitivity in the comet assay. Human whole blood, isolated lymphocytes and V79
      cells were treated with alkylating agents and post-incubated with FPG. FPG
      strongly enhanced MMS- and EMS-induced DNA damage but had no significant effect
      on ENU-induced DNA damage, indicating that the amount of N-7 guanine alkylation
      is responsible for the observed effect. Reducing the pH during alkali unwinding
      and electrophoresis to 12.5 to avoid the contribution of ALS to the comet assay
      effects, strongly decreased the sensitivity of the comet assay with and without
      FPG treatment and prevented DNA migration. We conclude that enhanced DNA effects
      in the comet assay by FPG after exposure to genotoxins with unknown mode of
      action should not directly be regarded as evidence for the presence of oxidative
      damage. Furthermore, reducing the pH leads to a considerable loss in sensitivity
      and should not be used in biomonitoring and other applications which require a
      sensitive protocol.

PMID- 14643968
TI  - Glycoprotein isolated from Ulmus davidiana Nakai inhibits TPA-induced apoptosis
      through nuclear factor-kappa B in NIH/3T3 cells.
AB  - Glycoprotein of Ulmus davidiana Nakai (UDN glycoprotein) was isolated and
      identified using SDS-PAGE. UDN glycoprotein was shown to have strong scavenging
      activities against oxygen free radicals, as detected by different oxygen-radical
      formation assays. To investigate the anti-apoptotic effects of UDN glycoprotein,
      we investigated the activity of protein kinase C alpha (PKCalpha), the DNA
      binding activation of nuclear factor-kappa B (NF-kappaB), the production of
      nitric oxide (NO) and apoptosis in 12-O-tetradecanoylphorbol 13-acetate (TPA)
      stimulated NIH/3T3 cells using a western blot analysis, electrophoretic mobility
      shift assays (EMSA) and NO assays. Results in this experiment showed that 100
      microg/ml of UDN glycoprotein has inhibitory effects on PKCalpha translocation,
      NF-kappaB DNA binding activity, NO production, and apoptosis in TPA (61.68 ng/ml)
      stimulated NIH/3T3 cells. Interestingly however, it could not regulate the DNA
      binding activity of AP-1. Therefore, UDN glycoprotein, a natural anti-oxidant, is
      a potential modulator of apoptotic signal pathways in NIH/3T3 cells.

PMID- 14643969
TI  - Cadmium exposure differentially modifies the circadian patterns of norepinephrine
      at the median eminence and plasma LH, FSH and testosterone levels.
AB  - This work was designed to analyze the cadmium effects on time-of-day variations
      of norepinephrine (NE) content in median eminence and on plasma levels of
      luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone in
      adult male rats. Rats were given cadmium at a dose of 25 ppm of cadmium chloride
      (CdCl(2)) in the drinking water for 1 month. Significant 24-h changes of NE
      content in the median eminence, plasma LH and testosterone levels occurred in
      control animals. Cadmium exposure induced a phase advance of the nocturnal peak
      of NE content that was described in the control group, to 12h and increased its
      amplitude. However, the mean NE content was not changed by cadmium. Metal
      exposure abolished the daily pattern of plasma LH levels, although the mean
      levels of the hormone were not modified by cadmium. For testosterone, the metal
      increased the amplitude of its nocturnal peak and induced the appearance of
      another peak during the light phase at 12h, thus increasing the mean plasma
      levels of this hormone. An interaction between the metal and time for NE and
      plasma testosterone levels was observed. These data suggest that cadmium exerts
      differential effects at the median eminence, the pituitary and the testes, that
      may explain the changes in the 24-h pattern of plasma testosterone levels.

PMID- 14643970
TI  - A comparison of human H295R and rat R2C cell lines as in vitro screening tools
      for effects on aromatase.
AB  - In this study we evaluated the rat Leydig cell carcinoma cell line R2C and the
      human adrenocorticocarcinoma cell line H295R for their suitability as in vitro
      screening tools for potential interference of xenobiotics with aromatase
      activity. A 24h exposure to prochloraz (PRO), fadrozole (FAD) and epoxyconazole
      (EPO) resulted in complete catalytic inhibition in H295R and R2C cells. In H295R
      cells, PRO and FAD were mixed-type inhibitors with apparent K(i) values of 0.04
      and 0.03 microM, and apparent K(i)' values of 0.33 and 0.06 microM, respectively.
      EPO was a competitive inhibitor with an apparent K(i) value of 0.51microM. In
      R2C, all three compounds showed mixed type inhibition kinetics, with apparent
      K(i) values (microM) of 0.004, 0.003 and 0.07, and apparent K(i)' values (microM)
      of 0.41, 0.01 and 2.42, respectively. Exposure for 24h of H295R cells to 8-bromo
      cyclic adenosine monophosphate (8-Br-cAMP), prostaglandin E2 (PGE2), phorbol 12
      myristate 13-acetate (PMA), or dexamethasone (DEX) resulted in 4.0, 2.8, 3.6 or
      3.6-fold induction of aromatase activity, respectively, as well as in an increase
      of several human aromatase transcripts with promoter-specific 5'-ends (pII and
      I.3). In R2C cells, only PMA slightly induced aromatase activity. A 24h exposure
      of H295R cells to atrazine (ATR), resulted in a three-fold induction of aromatase
      activity and a slight increase in pII and I.3 aromatase transcripts. However, ATR
      did not induce aromatase activity in R2C cells. We conclude that the H295R cell
      line contains aromatase promoter regions, which are responsive to the respective
      stimulants. They play a role in aromatase regulation in various tissues such as
      brain, placenta, healthy and diseased gonadal and breast tissue and therefore,
      they may play an important role in tumor genesis, development, behavior and
      reproduction. The H295R cell line may therefore be a relevant and useful tool in
      risk assessment of xenobiotics. The R2C cell line, although not suitable for
      studying induction, appears to be a more sensitive cell line for studying
      inhibitory effects of xenobiotics on aromatase activity.

PMID- 14643971
TI  - Coating of pellets with micronized ethylcellulose particles by a dry powder
      coating technique.
AB  - Pellets were coated with ethylcellulose powder to achieve extended release. The
      film forming ability of ethylcellulose powder and the effect of formulation
      factors (plasticizer type and concentration) and curing conditions (curing
      temperature and time) were investigated. The coating formulation was divided into
      two components consisting of a powder mixture (polymer plus talc) and a mixture
      of liquid materials (plasticizer plus binder solution), which were sprayed
      separately into the coating chamber of a fluidized bed coater (Glatt GPCG-1,
      Wurster insert). The coated pellets were oven-cured under different conditions
      (60-80 degrees C, 2-24 h) without and with humidity (100% relative humidity).
      Propranolol hydrochloride was used as a model drug, and drug release was studied
      in 0.1 N HCl at 37 degrees C (USP XXV paddle method). Despite the high glass
      transition temperature of ethylcellulose (133.4 degrees C), micronized
      ethylcellulose powder can be used for dry powder coating by adjusting the coating
      temperature, amount and type of plasticizer applied, and curing conditions. 40%
      plasticizer and a curing step (80 degrees C, 24 h) were required to achieve
      complete coalescence of the polymer particles and extended drug release of coated
      pellets. Although ethylcellulose-coated pellets had an uneven surface, extended
      drug release could be obtained with coating level of 15%. Because of its high
      glass transition temperature, ethylcellulose-coated pellets showed unchanged drug
      release profiles upon storage at room temperature for 3 years.

PMID- 14643972
TI  - Evaluation of oral formulations of gentamicin containing labrasol in beagle dogs.
AB  - Gentamicin (GM) is a polarized water-soluble compound having very poor intestinal
      membrane permeability resulting in low oral bioavailability. Labrasol was found
      to improve the intestinal absorption of GM in rats. In the present study, GM
      formulations containing labrasol were evaluated in beagle dogs after filling into
      hydroxypropylmethyl cellulose (HPMC) capsules wrapped with Eudragit L100 (Eud L)
      and Eudragit S100 (Eud S) films. The results of the in vitro drug release studies
      could not differentiate between two kinds of enteric capsules and among the three
      kinds of GM formulations. Oral administration of GM solution at a dose of 50.0 mg
      per dog of GM and 0.60 ml per dog of labrasol has resulted in Cmax values of 2.38
      +/- 0.50 microg/ml and 2.30 +/- 0.42 microg/ml with Eud L and Eud S capsules,
      respectively. The AUC values obtained were also higher at 4.35 +/- 1.31 microg
      h/ml and 5.34 +/- 0.95 microg h/ml with Eud L and Eud S capsules, respectively.
      Formulation of GM as a suspension in labrasol has resulted in the decrease of
      Cmax values by two to four times and AUC values by > 2.5 times compared to the
      solution formulation. The above results indicate that solution formulation was
      better over the suspension. An absorbent, synthetic sponge was used to absorb GM
      solution formulation and encapsulated with Eud L and Eud S capsules. The Cmax and
      AUC values obtained with sponge formulation were higher than those of suspension
      formulations but were lower than solution formulations. There was no significant
      difference in the extent of GM absorption between Eud L and Eud S capsules used
      for encapsulating GM formulations.

PMID- 14643973
TI  - Preparation and characterization of injectable microspheres of contraceptive
      hormones.
AB  - Present study describes the development of a new formulation of levonorgestrel
      and ethinylestradiol based on double emulsion-solvent evaporation technique using
      poly(epsilon-caprolactone) (PCL) as biodegradable polymer. The effect of polymer
      concentration on microspheres and entrapment of drug into microspheres were
      studied. PCL was selected because of its hydrophobicity and advantages over other
      biodegradable polymers. Characterization of biodegradable polymer used for
      controlled drug delivery is essential to ensure reproducibility of in vitro and
      in vivo performances. The selected characterisation techniques established for
      PCL microspheres include its loading and entrapment efficiencies, DSC to analyse
      thermal behaviour, SEM to observe surface morphology, drug content of
      microspheres and in vitro release of drugs from microspheres. The SEM reports
      showed that microspheres were with smooth surface and DSC thermograms revealed no
      interaction between drug and polymer. The entrapment was found to be 58 and 47%
      for 1:10 and 1:5 batches and in vitro release studies showed that about 69.7% of
      LNG and 66.7% of EE from 1:10 batch and about 80% of LNG and 75.5% of EE from 1:5
      batch for 150 days.

PMID- 14643974
TI  - Therapeutic efficacy study of novel 5-FU-loaded PMM 2.1.2-based microspheres on
      C6 glioma.
AB  - The aim of this study was to evaluate the potential of poly(methylidene malonate
      2.1.2) as a new drug delivery system to the central nervous system. 5
      Fluorouracil microspheres were formulated by an emulsion-extraction method, and
      evaluated on a C6 glioma model. Twenty-seven Sprague-Dawley female rats underwent
      implantation of various C6 cell concentrations. Magnetic resonance imaging was
      performed at day 10 to control the setting of the tumor, by using a T2-weighted
      sequence. At day 12, 18 animals received blank or 5-FU-loaded microspheres, while
      9 animals were not implanted and constituted the controls. Thereafter, MRI was
      performed twice a week to follow the tumor growth. In 12 animals, an alloimmune
      rejection of the tumor was observed, showing the limitations of the C6 glioma
      model. When tumor developed, no relationship was observed between the number of
      C6 cells injected and the tumor volume. 5-FU microsphere efficacy could
      statistically be demonstrated by significantly improving the median survival of
      C6 glioma-bearing animals and also by decreasing tumor burden.

PMID- 14643975
TI  - Ketoprofen: release from, permeation across and rheology of simple gel
      formulations that simulate increasing dryness.
AB  - The migration of ketoprofen through a series of simple gels that varied in
      solvent composition to simulate snapshots of a dynamically drying topical
      formulation was studied. Firstly, the release rate of ketoprofen was determined
      from formulations based on Cabosil and PEG 400, the proportion of which was
      varied to mimic progressively dryer states. Secondly, the apparent permeability
      of ketoprofen across the corresponding blank Cabosil gels was determined.
      Thirdly, the effect of macro viscosity on these data was probed by comparing
      permeation of ketoprofen across Cabosil and hydroxypropyl cellulose (HPC) gels of
      equal viscosity. Linear release profiles were produced for all formulations
      suggesting first-order release and the rate of ketoprofen liberated was inversely
      to the proportion of Cabosil, suggesting that the drier the film, the slower the
      rate of release. At the lowest level of thickener used (5%) the release rate was
      reduced to 45% of the control. At 25% the release rate was reduced to 24% of the
      control. The presence of the Cabosil had an even more dramatic effect on the
      apparent permeability of ketoprofen across the gels. At 5% Cabosil the apparent
      steady state flux was reduced to 4% of the control. At 25% the apparent steady
      state flux was reduced to < 1% of the control. Although the 0.5% HPC gel and the
      1% Cabosil gel possessed identical macro viscosities, the permeation of
      ketoprofen through the HPC gel was almost double that of the Cabosil gel. The
      data from these experiments demonstrated that migration of active molecules
      through a gel is significantly affected by the amount of solvent present in, or
      lost from, the system. It is proposed that increased adsorption of active to the
      thickener plays a more important role than increased macro viscosity for reduced
      active release as the formulation becomes increasingly dry. Furthermore, such
      affects are profoundly influenced by the chemical nature of the thickener.

PMID- 14643976
TI  - Encapsulation and release of the hypnotic agent zolpidem from biodegradable
      polymer microparticles containing hydroxypropyl-beta-cyclodextrin.
AB  - The goal of this study was to design a prolonged release system of the hypnotic
      agent zolpidem (ZP) useful for the treatment of insomnia. In this work, ZP alone
      or in the presence of HP-beta-CD was encapsulated in microparticles constituted
      by poly(DL-lactide) (PDLLA) and poly(DL-lactide-co-glycolide) (PLGA) and the drug
      release from these systems was evaluated. ZP alone-loaded microparticles were
      prepared by the classical O/W emulsion-solvent evaporation method. Conversely,
      ZP/HP-beta-CD containing microparticles were prepared by the W/O/W emulsion
      solvent evaporation method following two different procedures (i.e. A and B).
      Following procedure A, the previously produced ZP/HP-beta-CD solid complex was
      added to the water phase of primary emulsion. In the procedure B, HP-beta-CD was
      added to the aqueous phase and ZP to the organic phase. The resulting
      microparticles were characterized about morphology, size, encapsulation
      efficiency and release rates. FT-IR, X-ray, and DSC results suggest the drug is
      in an essentially amorphous state within the microparticles. The release profiles
      of ZP from microparticles were in general biphasic, being characterized by an
      initial burst effect and a subsequent slow ZP release. It resulted that co
      encapsulating ZP with or without HP-beta-CD in PDLLA and PLGA the drug release
      from the corresponding microparticles was protracted. Moreover, in a preliminary
      pharmacological screening, the ataxic activity in rats was investigated and it
      was found that intragastric administration of the ZP/HP-beta-CD/PLGA
      microparticles prepared according to procedure B produced the same ataxic
      induction time as the one induced by the currently used formulation Stilnox.
      Interestingly moreover, there was a longer ataxic lasting and a lower intensity
      of ataxia produced by the ZP/HP-beta-CD/PLGA-B-formulation already after 60 min
      following the administration. However, a need for further pharmacokinetic and
      pharmacodynamic studies resulted to fully evaluate the utility of this last
      formulation for the sustained delivery of ZP.

PMID- 14643977
TI  - The choice of a compressor for the aerosolisation of tobramycin (TOBI) with the
      PARI LC PLUS reusable nebuliser.
AB  - The performance of five different compressors (CR60), Porta-Neb, Pulmo-Aide,
      TurboBoy and Freeway Freedom) was studied in combination with the widely
      recommended PARI LC PLUS nebuliser for the aerosolisation of a marketed
      tobramycin solution (TOBI). The droplet size distribution of the generated
      aerosol was measured with laser diffraction technique at stationary inspiratory
      flow rates through the nebuliser cup of 20, 30 and 40l N/min. The different
      compressors showed a distinct difference in droplet size distribution of the
      aerosol and nebulisation time till dry running. The finest droplets with a volume
      (equals mass) median diameter (mmd) of 1.84 microm (which was the same at all
      flow rates), as well as the narrowest size distribution were obtained with a
      CR60. The Freeway Freedom generated the largest droplets: mmd ranged between 2.63
      and 3.72 microm depending on the inspiratory flow rate. The aerosol produced with
      this compressor also had the widest size distribution. The differences between
      the compressors could be explained with differences in the jet flow. A higher jet
      flow resulted in finer droplets, less dependence on the inspiratory flow rate and
      a shorter time till dry running. Thus, to obtain the required fineness of the
      aerosol for peripheral airway deposition of the tobramycin, independent of the
      inspiratory flow rate, the use of the CR60 compressor is preferred over the use
      of Porta-Neb, Pulmo-Aide, TurboBoy and Freeway Freedom (in order of decreasing
      preference). Finally, it was found that careful cleaning with warm water and
      liquid soap of the nebuliser cup is essential to obtain adequate performance of
      the LC PLUS.

PMID- 14643978
TI  - Effect of poly-hydroxy aliphatic ester polymer type on amoxycillin release from
      cylindrical compacts.
AB  - The objective of the work was to investigate the effects of a range of poly
      hydroxy aliphatic esters (poly-lactide (PLA) and poly-lactide-co-glycolide
      (PLGA)) of different molecular weight and composition on the release and
      stability of the amphoteric drug amoxycillin. The effect of this amphoteric drug
      on the extent and kinetics of polymer degradation was also investigated. The
      polymers were used to prepare drug-free and drug-loaded cylindrical discs. Drug
      release profiles were determined while changes in polymer composition were
      monitored by weight loss and molecular weight change. The extent of drug release
      was highly dependent on polymer molecular weight and composition, with earlier
      complete release occurring with the lower molecular weight and lower lactide
      containing polymers. A larger proportion of drug was released by polymer
      degradation control with the higher lactide containing polymer. The proportion of
      drug released intact was influenced by the polymer molecular weight, with a
      greater proportion of intact drug being released from the higher molecular weight
      systems. The inclusion of amoxycillin influenced polymer degradation and resulted
      in slower polymer hydrolysis. Model parameters obtained for polymer degradation
      indicated that this retardation effect increased with increasing lactide content
      of the polymer. The results suggest that small amounts of amoxycillin or its
      degradation products may bind or cross link with the polymers, thus retarding
      their degradation.

PMID- 14643979
TI  - Screening for yeast with antibacterial properties from an ethanol distillery.
AB  - A general screening for the expression of antibacterial activity and non
      flocculating type of yeast strains from must and fermented broth of alcohol
      distilleries was performed. From 60 strains only Saccharomyces sp. M26 presented
      a inhibitory halo in Lactobacillus fermentum culture and significant reduction in
      the culture turbidity (71%) and specific growth rate (56%) when compared to the
      control. Freezing did not affect the antibacterial activity of the Saccharomyces
      sp. M26 extract and heating at 90 degrees C for 20 min completely destroyed this
      activity. It is expected the decrease of lactic acid bacteria growth in the S.
      cerevisiae alcoholic fermentation should allow for better control of these
      bacteria in the process.

PMID- 14643980
TI  - Activity and elution profile of laccase during biological decolorization and
      dephenolization of olive mill wastewater.
AB  - The performance and enzymatic strategy exhibited by basidiomycete Euc-1, a
      laccase producing strain, was investigated during the biodegradation of olive
      mill wastewater (OMW). This strain yielded better decolorization of solidified
      OMW than Phanerochaete chrysosporium and removed 90% of phenols (initial
      concentration=800 mg l(-1)), 73% of color (initial A465=4.4), and 45% of chemical
      oxygen demand in batch cultures containing OMW. Since partial phenol removal
      occurred before the detection of enzymatic activity, no plausible correlation
      could be established between them. In contrast, decolorization occurred only
      after the detection of laccase activity and coincided with its production over
      time. Two laccase fractions (Lac1 and Lac2) were separated by chromatography. OMW
      strongly induced Lac2 that was almost absent in defined liquid medium.
      Furthermore, Lac2 was the main laccase fraction in the presence of OMW. This
      study pointed out that basidiomycete Euc-1 and its ligninolytic system could be a
      useful tool for the bioremediation of wastewater generated in the process of
      olive oil extraction.

PMID- 14643981
TI  - Ethanol recovery from corn fiber hydrolysate fermentations by pervaporation.
AB  - Corn fiber, a byproduct of corn wet milling, is an attractive feedstock for
      biomass ethanol production. Corn fiber was hydrolyzed by dilute sulfuric acid and
      neutralized by one of two methods: conventional lime treatment or neutralization
      by strongly basic anion exchange. The anion exchange neutralized (AEN)
      hydrolysate contained substantially lower levels of the inhibiting compounds
      furfural, 5-hydroxymethylfurfural, and acetic acid compared to the lime
      neutralized hydrolysate. In batch fermentations the ethanol yields and final
      ethanol concentration of the two hydrolysates were similar at 0.32-0.43 g/g and
      29-44 g/l, respectively. Sugar consumption in the AEN fermentations was superior.
      Coupling of a membrane pervaporation unit to a fed-batch fermentation of AEN
      hydrolysate maintained the ethanol concentration below 25 g/l with complete sugar
      utilization for approximately 5 days. A concentrated ethanol stream of 17 wt.%
      ethanol was produced by the pervaporation unit.

PMID- 14643982
TI  - Dilute acid hydrolysis of presscakes from silage and grass to recover
      hemicellulose-derived sugars.
AB  - Grass and silage presscakes from various types of raw materials were hydrolyzed
      with dilute acid at moderate conditions to recover hemicellulose-derived sugars.
      Extracting the material with cold water prior to hydrolysis significantly
      increased the yield. The poor performance without extraction was due to the high
      buffer capacity of the material. The best results were obtained with extracted
      grass and silage from a permanent pasture and extracted clover/grass silage. The
      highest observed sugar yield was 16.43 g/100 g dry-matter, which represents
      approximately 25% of the available sugars and 60% of the hemicellulose fraction.
      Including the soluble sugar oligomers, the yields were even higher (up to 20
      g/100 g dry-matter). A statistical experiment design with extracted clover/grass
      silage was performed to estimate the effects of temperature, time, and dry-matter
      concentration. Acid and dry-matter concentration had the highest effect on sugar
      yield, whereas temperature and acid concentration were mainly responsible for
      forming sugar degradation products. These findings agree with recent kinetic
      theories. Yields in this experiment were comparable to those of other
      lignocellulosic materials.

PMID- 14643983
TI  - Decolorization of molasses wastewater by a strain No.BP103 of acetogenic
      bacteria.
AB  - Among 170 strains of acetogenic bacteria, a strain No.BP103 showed the highest
      decolorization yield (76.4+/-3.2%) when cultivated at 30 degrees C for 5 days in
      molasses pigments medium containing glucose 3.0%, yeast extract 0.5%, KH2PO4 0.1%
      and MgSO4 x 7H2O 0.05% and the pH adjusted to 6.0. In addition this strain could
      decolorize 32.3+/-3.2% and 73.5+/-3.5% of molasses pigments in stillage and
      anaerobically treated molasses wastewater, both supplementing glucose 3.0%, yeast
      extract 0.5%, KH2PO4 0.1% and MgSO4 x 7H2O 0.05%. However without nutrients
      supplement, the decolorization yields were 9.75+/-3.0% and 44.36+/-3.4%,
      respectively. In a replacement culture system involving six times replacement (30
      days), the strain No.BP103 showed a constant decolorization yield of 72.0+/-3.2
      84.0+/-3.2% and caused decreases of biological oxygen demand and chemical oxygen
      demand values of approximately 58.5+/-6.4-82.2+/-7.1% and 35.5+/-0.42-71.20.58%,
      respectively. Under a periodical feeding system, the decolorization yield was
      30.0+/-2.1-45.0+/-3.5%.

PMID- 14643984
TI  - Production of Botrytis cinerea for potential introduction into a vineyard.
AB  - Botrytis cinerea was produced in solid-phase fermentation, liquid fermentation
      and on potato dextrose agar. Stored products were evaluated for grape
      colonization in grape bioassays and in field trials, and for B. cinerea density
      using colony forming unit analyses and a nucleic-acid-based method. B. cinerea
      colony forming unit density was significantly correlated to the probability of
      successful grape colonization in grape bioassays (p-value=0.0002). Solid
      fermentation products could be stored longer than liquid fermentation and potato
      dextrose agar products. There was little difference in the rate of grape
      colonization in laboratory bioassays among solid-phase fermentation, liquid
      fermentation and plate culture products. Although the initial B. cinerea
      colonization rate of field grapes was slightly greater on vines treated with
      solid-phase fermentation and plate culture products compared to vines treated
      with product from liquid fermentation, there was no significant difference in
      final colonization between vines treated with solid-phase fermentation, liquid
      fermentation and plate culture products and untreated vines.

PMID- 14643985
TI  - Optimization of cyclodextrin production from sago starch.
AB  - Cyclodextrin (CD) is synthesized by bacterial cyclodextrin glycosyltransferase
      (CGTase) and is widely used in food, pharmaceutical, cosmetic, and agricultural
      industries. In this study, Bacillus circulans CGTase was partially purified by
      ammonium sulfate precipitation at 50-70% saturation. The optimum pH and
      temperature for CD production from sago starch were found to be in the ranges of
      4.5-5.0 and 55-60 degrees C, respectively. beta-CD was the predominant product,
      constituting 65% of all CD products. The beta-CD produced using partially
      purified and crude CGTase were compared and found to have no significant
      difference in yield and productivity. The appropriate proportion of CGTase to
      sago starch for beta-CD production was determined by response surface
      methodology. The most appropriate enzyme:substrate ratio was 50 U g sago starch(
      1) CGTase and 60 g l(-1) sago starch.

PMID- 14643986
TI  - Synthesis and characterization of vegetable oil derived esters: evaluation for
      their diesel additive properties.
AB  - Trans-esterification of four vegetable oils; canola oil, greenseed canola oil
      from heat-damaged seeds, processed waste fryer grease and unprocessed waste fryer
      grease, was carried out using methanol, and KOH as catalyst. The methyl esters of
      the corresponding oils were separated from the crude glycerol, purified, and
      characterized by various methods to evaluate their densities, viscosities, iodine
      values, acid numbers, cloud points, pour points and gross heat of combustion,
      fatty acid and lipid compositions, lubricity properties, and thermal properties.
      The fatty acid composition suggests that 80-85% of the ester was from unsaturated
      acids. Substantial decrease in density and viscosity of the methyl esters
      compared to their corresponding oils suggested that the oils were in their mono
      or di glyceride form. The lubricity of the methyl esters, when blended at 1 vol%
      treat rate with ISOPAR M reference fuel, showed that the canola methyl ester
      enhanced the fuel's lubricity number. From the analyses performed, it was
      determined that the ester with the most potential for being an additive or a
      substitute for diesel fuel is the canola methyl ester, whose physical and
      chemical characteristics are similar to diesel fuel.

PMID- 14643987
TI  - Influence of rice straw cooking conditions in the soda-ethanol-water pulping on
      the mechanical properties of produced paper sheets.
AB  - A normalized design was used to examine the influence of independent variables
      (alcohol concentration, cooking time and temperature) in the catalytic soda
      ethanol pulping of rice straw on various mechanical properties (breaking length,
      burst, tear index and folding endurance) of paper sheets obtained from each
      pulping process. An equation of each dependent variable as a function of cooking
      variables (independent variables) was obtained by multiple non-linear regression
      using the least square method by MATLAB software for developing of empirical
      models. The ranges of alcohol concentration, cooking time and temperature were 40
      65% (w/w), 150-180 min and 195-210 degrees C, respectively. Three-dimensional
      graphs of dependent variables were also plotted versus independent variables. The
      optimum values of breaking length, burst and tear index and folding endurance
      were 4683.7 (m), 30.99 (kN/g), 376.93 (mN m2/g) and 27.31, respectively. However,
      short cooking time (150 min), high ethanol concentration (65%) and high
      temperature (210 degrees C) could be used to produce papers with suitable burst
      and tear index. However, for papers with best breaking length and folding
      endurance low temperature (195 degrees C) was desirable. Differences between
      optimum values of dependent variables obtained by normalized design and
      experimental data were less than 20%.

PMID- 14643988
TI  - Mango seed uses: thermal behaviour of mango seed almond fat and its mixtures with
      cocoa butter.
AB  - This paper deals with the physicochemical characterization, including thermal
      behaviour, by differential scanning calorimetry of mango seed almond fat (MAF),
      alone and in mixtures with cocoa butter (CB). Results showed that mango almond
      seeds contain about 5.28-11.26% (dw) of fat. The refraction index is 1.466, the
      saponification index 189.0 and the iodine index 41.76. Fatty acids found in MAF
      are oleic, stearic, and palmitic acids (40.81%, 39.07% and 9.29% (w/w),
      respectively) as well as smaller amounts of linoleic, with arachidic, behenic,
      lignoceric, and linolenic acids, among others. Calorimetric analysis showed that
      MAF crystallizes between 14.6 and -24.27 degrees C with a DeltaHc of 56.06 J/g
      and melts between -17.1 and 53.8 degrees C, with fusion maxima at 18.54 degrees C
      and 40.0 degrees C for the alpha and beta polymorphic forms. Their fusion
      enthalpies are 70.12 and 115.7 J/g. The MAF solids content profile is very
      similar to that of CB, both in stabilized and non-stabilized samples. The mixing
      compatibility was analyzed using isosolids curves of mixtures of different
      compositions.

PMID- 14643989
TI  - Adsorption of chromium from aqueous solution on treated sawdust.
AB  - The adsorption of Cr(VI) from aqueous solutions on formaldehyde treated sawdust
      (SD) and sulphuric acid treated sawdust carbon (SDC) of Indian Rosewood, a timber
      industry waste, was studied at varying Cr(VI) concentrations, adsorbent dose, pH
      and agitation time. Similar experiments were conducted with commercially
      available coconut based activated carbon to compare the results. The Cr(VI)
      adsorption efficiency on SDC was higher than SD. The adsorption followed first
      order rate expression and Lagergren equation. An initial pH of 3.0 was most
      favorable for Cr(VI) removal by both the adsorbents. Maximum Cr(VI) was
      sequestered from the solution within 60 min after the beginning for every
      experiment. It is proposed that SDC and SD can be potential adsorbents for Cr(VI)
      removal from dilute solutions.

PMID- 14643990
TI  - Emission performance and combustion efficiency of a conical fluidized-bed
      combustor firing various biomass fuels.
AB  - This paper summarizes the results of an experimental study on combustion of three
      distinct biomass fuels (sawdust, rice husk and pre-dried sugar cane bagasse) in a
      single fluidized-bed combustor (FBC) with a conical bed using silica sand as the
      inert bed material. Temperature, CO, NO and O2 concentrations along the combustor
      height as well as in flue (stack) gas were measured in the experimental tests.
      The effects of fuel properties and operating conditions (load and excess air) on
      these variables were investigated. Both CO and NO axial profiles were found to
      have a maximum whose location divides conventionally the combustor volume into
      formation (lower) and reduction (upper) regions for these pollutants. Based on CO
      emission and unburned carbon content in fly ash, the combustion efficiency of the
      conical FBC was quantified for the selected biomass fuels fired under different
      operating conditions.

PMID- 14643991
TI  - Reduction of vanadium(V) with Acidithiobacillus ferrooxidans and
      Acidithiobacillus thiooxidans.
AB  - Biotechnological leaching has been proposed as a suitable method for extraction
      of vanadium from spent catalysts and oil ash. In the biological leaching process,
      the vanadium(V) can be reduced to vanadium(IV), which is a less toxic and more
      soluble form of the vanadium. The present investigation showed that
      Acidithiobacillus ferrooxidans efficiently reduced vanadium(V) in the form of
      vanadium pentaoxide, to vanadyl(IV) ions, and tolerated high concentrations of
      vanadium(IV) and vanadium(V). A. ferrooxidans was compared with Acidithiobacillus
      thiooxidans, which has previously been utilized for vanadium leaching and
      reduction. Vanadium pentaoxide and sodium vanadate were used as model compounds.
      The results of this study indicate possibilities to develop an economical and
      technically feasible process for biotechnological vanadium recovery.

PMID- 14643992
TI  - Enhancement of citric acid production with ram horn hydrolysate by Aspergillus
      niger.
AB  - The potential use of ram horn hydrolysate (RHH) as a supplement for improvement
      of citric acid production by Aspergillus niger NRRL 330 was studied. For this
      purpose, first RHH was produced. Ram horns were hydrolyzed by treating with acid
      (6 N-H2SO4) and the RHH was obtained. With the addition of RHH to the
      fermentation medium with a final concentration of 4% (optimal concentration),
      citric acid value reached a maximum value (94 g/l), which is 52% higher than that
      of the control experiment. The addition of 4% (v/v) RHH enhanced citric acid
      accumulation, reduced residual sugar concentration and stimulated mycelial
      growth. Adding 4% RHH had no adverse effects on A. niger. As a result, RHH was
      found to be suitable as a valuable supplement for citric acid production in the
      submerged fermentation.

PMID- 14643993
TI  - An economical bioreactor for evaluating biogas potential of particulate biomass.
AB  - An economical bioreactor designed for evaluating the biogas potential of
      particulate biomass is described. The bioreactor uses a simple stirring
      apparatus, called the Bordeaux stirrer, to enable gas-tight mixing of
      fermentation cultures. The apparatus consists of a low-rpm motor connected to a
      bent steel stir rod, which is placed in a length of flexible plastic tubing
      inserted through a rubber stopper in a gas-tight manner. This stirrer is suitable
      for providing intermittent or continuous mixing in bench-scale anaerobic cultures
      containing particulate biomass. The reactor system may be operated as a batch-fed
      or semi-continuously fed digester. This communication documents the advantages of
      the stirring apparatus, describes the details of reactor fabrication and
      operation, and outlines the type of experimental work for which the bioreactor is
      suitable.

PMID- 14643994
TI  - Systematic review of antidepressant therapies in Parkinson's disease.
AB  - Depression is the most common psychiatric disturbance in Parkinson's disease. We
      conducted a Cochrane systematic review to assess the efficacy and safety of
      antidepressant therapies in idiopathic Parkinson's disease. Relevant trials were
      identified from electronic databases, reference lists and queries to
      antidepressant manufacturers. Three randomised controlled trials examined oral
      antidepressants in 106 patients with Parkinson's disease. No eligible trials of
      electroconvulsive or behavioural therapy were found. In the first arm of the
      crossover trial by Andersen et al. (n=22), nortriptyline treated patients showed
      a larger improvement than placebo in a unique depression rating scale after 16
      weeks although significance levels were not provided. A parallel group trial by
      Wermuth et al. (n=37) did not show any significant difference between citalopram
      and placebo in Hamilton score after 52 weeks. Rabey et al. (n=47) performed an
      open-label trial comparing fluvoxamine with amitriptyline. Similar numbers in
      each group had a 50% reduction in Hamilton score after 16 months. Major side
      effects including visual hallucinations and confusion were reported with
      fluvoxamine and amitriptyline. Insufficient data on the effectiveness and safety
      of antidepressant therapies in Parkinson's disease are available on which to make
      recommendations for their use. Large scale randomised controlled trials are
      urgently required.

PMID- 14643995
TI  - The risk of bladder and autonomic dysfunction in a community cohort of
      Parkinson's disease patients and normal controls.
AB  - A questionnaire investigating bladder problems, symptoms of autonomic
      dysfunction, social handicap and depression was mailed to a sample of patients
      with Parkinson's disease (PD) and to elderly control subjects without PD. The
      patients reported two-fold greater risk of bladder problems and four-fold risk of
      autonomic problems compared to the controls. Erectile dysfunction was nearly
      twice as frequent in patients compared to controls. Depressive symptoms in the PD
      group were predictive of bladder problems and autonomic impairment and also
      poorer social functioning and dependency in activities of daily living. No
      associations between bladder and autonomic dysfunction, age, or severity/duration
      of PD were found. This investigation shows that the risk of bladder, autonomic
      and erectile dysfunction is significantly greater in patients with PD compared to
      a control group.

PMID- 14643996
TI  - Neuropsychological changes after subthalamic nucleus stimulation: a 12 month
      follow-up in nine patients with Parkinson's disease.
AB  - Deep brain stimulation of the subthalamic nucleus has been recognized as one of
      the most promising techniques to decrease 'off' motor symptoms and motor
      fluctuations, allowing a reduction of drug therapy and limiting side effects of
      drug therapy. However, there is still open debate on the possible consequences of
      chronic subthalamic stimulation on general cognitive performance. A general
      amelioration of cognitive performance, in particular of executive functions has
      been reported but results are not homogeneous. We studied nine patients with
      Parkinson's Disease for 12 months following surgery for deep stimulation,
      studying their cognitive performances, paying particular attention to linguistic
      tests and selective alternating words production. Our results may be consistent
      with a slowing of cognitive activity, with a reduction of quantitative
      production, but with an increase in control of linguistic production, which is
      more precise and definite. We discuss the possible significance of these results,
      fully aware that only nine patients were involved, and that the potential for
      generalization is seriously limited, with a particular overview on the frontal
      subthalamic pathway, which in our opinion is responsible for the results we
      observed.

PMID- 14643997
TI  - Thalamic deep brain stimulation for tremor-predominant Parkinson's disease.
AB  - OBJECTIVES: Determine the long-term efficacy of thalamic deep brain stimulation
      (DBS) for treatment of tremor among individuals with tremor-predominant
      Parkinson's disease (PD).Design. Longitudinal, unblinded assessment of tremor and
      activities of daily living (ADL) at baseline (pre-surgical), and post-operative
      intervals of 1, 3, and 12 months, and annually thereafter up to 3 years. METHODS:
      A clinical series of 19 individuals undergoing placement of a DBS system for
      treatment of PD-related tremor. A battery of subjective and objective measures of
      tremor was completed at planned pre- and post-operative intervals. RESULTS:
      Stimulation was associated with significant improvement on subjective and
      objective measures of ADL performance, midline tremor, and contralateral upper
      and lower extremity tremor, including parkinsonian resting and action tremors,
      over the follow-up period. Ipsilateral tremor showed little or no effect of
      stimulation after the first 3 months. Antiparkinsonian medication use and
      stimulation parameters showed little or no change over the course of follow-up.
      About half (53%) of all individuals reported at least one side effect, generally
      mild, during the follow-up period, with paresthesias and dysarthria being the
      most common. A total of two leads required replacement due to (1) infection, and
      (2) adverse side effects (i.e. burning and tingling with stimulation).
      CONCLUSION: DBS is associated with stable tremor control in PD. Side-effects are
      typically easily managed with stimulation adjustments, although in some cases
      lead replacement may be required.

PMID- 14643998
TI  - International use of health status questionnaires in Parkinson's disease:
      translation is not enough.
AB  - The present study assessed the linguistic and content validity of the Swedish
      version of the 39-item Parkinson's disease questionnaire (PDQ-39). The frame
      question, response alternatives and two of the 39 items yielded substantial
      linguistic and stylistic problems. Such shortcomings would be expected to
      influence responses to, and the quality of, the whole questionnaire. Data support
      content validity of the PDQ-39 as a functional health status questionnaire,
      although some shortcomings were identified. This preliminary study illustrates
      the need for documented linguistic validity before new language adaptations of
      patient-reported outcome measures can be considered suitable for use in clinical
      trials, research, and practice.

PMID- 14643999
TI  - Event-related potentials during visual S1-S2 paradigm in multiple system atrophy:
      relation to morphologic changes on brain MRI measurement.
AB  - Although mild cognitive deficits in multiple system atrophy (MSA) have been
      proved on neuropsychological testing, the cognitive function in MSA has not been
      investigated sufficiently from an electrophysiological view point. We performed a
      visual Event-related potential (ERP) examination and quantitative magnetic
      resonance imaging (MRI) measurements on 24 MSA patients and 18 normal subjects,
      and investigated the relationship between the ERP abnormalities and the
      morphological changes of the brain in MSA patients. To elicit ERPs, we used S1-S2
      task which needs frontal lobe function for execution. We found significant
      prolongation of P3 latency and reaction time and significant attenuation of P3
      amplitude in MSA, compared with normal control values. We performed the square
      and linear MRI measurements on MSA and normal subjects. The cerebellum, the pons,
      the perisylvian cerebral area and the deep cerebral gray matter in MSA were
      significantly smaller than those in normal subjects. The mean value in MSA was
      significantly increased for the bicaudate index and Huckman number compared with
      those in normal subjects. In MSA, we found significant correlation between P3
      latency and atrophy of the cerebellum and the pons, while we found no correlation
      between ERP abnormalities and quantitative MRI measurements of any other regions.
      Our results showed that the prolongation of visual P3 latency during S1-S2 task
      was significantly associated with atrophy of the cerebellum and the pons.

PMID- 14644000
TI  - Cutaneous sympathetic function and cardiovascular function in patients with
      progressive supranuclear palsy and Parkinson's disease.
AB  - Some procedures, such as deep inspiration, increase sweat output (SSwR;
      sympathetic sweat response) and reduce cutaneous blood flow (SVR; skin vasomotor
      reflex) on the palm. We investigated SSwR, SVR, and cardiovascular function in 12
      patients with progressive supranuclear palsy (PSP), 13 patients with Parkinson's
      disease (PD), and 9 healthy subjects. In the PSP patients, SSwR was severely
      diminished, whereas SVR was maintained and cardiovascular function was well
      preserved. In the PD patients, SSwR was relatively preserved, SVR was maintained,
      and some patients showed cardiovascular hypofunction. A combination of skin
      sympathetic and cardiovascular tests may be useful for distinguishing between PD
      and PSP.

PMID- 14644001
TI  - Deficits on Corsi's block-tapping task in early stage Parkinson's disease.
AB  - Cognitive deficits in Parkinson's disease (PD) include disturbances in working
      memory. We examined sequential visuo-spatial memory span by means of an
      adaptation of the Corsi Block-Tapping Task in groups of medicated (n=14) and non
      medicated (n=15) patients with early stage PD, and in control subjects (n=22). A
      deficit in memory span was found in medicated patients with early stage PD
      relative to controls. There were no differences between non-medicated patients
      relative to either controls or medicated patients. A decrease in sequential visuo
      spatial memory span appears to be a relatively early feature of PD and most
      likely reflects executive rather than mnemonic dysfunction.

PMID- 14644002
TI  - Paroxysmal kinesigenic dyskinesia associated with central pontine myelinolysis.

PMID- 14644003
TI  - Malignant syndrome in Parkinson's disease.

PMID- 14644004
TI  - Piribedil as an adjunct to levodopa in advanced Parkinson's disease: the Asian
      experience.
AB  - Data on the efficacy and tolerability of piribedil in Asians are scarce. Forty
      nine Filipino PD patients with motor fluctuations were enrolled in an 8-week
      trial of piribedil of up to 150 mg/day. Mean improvement was 48% for the motor
      UPDRS scores (tremor showed greatest change), and 43% for activities of daily
      living. Mean daily levodopa dose decreased by 17%, and mean duration of effect of
      levodopa increased by 1.3 h (45%). Most common side effects were hallucinations
      (20%), dyskinesias (20%), dizziness (8%), and sleepiness (6%). This trial shows
      that piribedil is effective and well-tolerated by Asian patients with advanced PD
      at least with short-term use.

PMID- 14644007
TI  - Conductances responsible for slow wave generation and propagation in interstitial
      cells of Cajal.
AB  - Interstitial cells of Cajal (ICC) are a fundamental component of the pacemaker
      apparatus of the gastrointestinal (GI) tract. ICC generate pacemaker currents
      that are the basis for slow wave activity in GI muscles. ICC form a network of
      cells connected by gap junctions that run around and along the phasic regions of
      the GI tract. ICC possess specialized conductances that allow them to generate
      pacemaker activity and serve as the pathway for active propagation of slow waves.
      Pacemaker currents are attributed to a Ca(2+)-inhibited, voltage-independent, non
      selective cation conductance that has similar properties to the conductance
      elicited by expression of transient receptor potential-C4. Propagation occurs
      through a voltage-dependent mechanism, and data suggest that the factor coupling
      pacemaker units in ICC is Ca(2+) entry. ICC express a dihydropyridine-resistant,
      voltage-dependent Ca(2+) conductance that is important in slow wave propagation.
      Work is underway to determine the molecular identities of these conductances.

PMID- 14644008
TI  - Ion channels in gastrointestinal smooth muscle and interstitial cells of Cajal.
AB  - A requirement for normal gastrointestinal motility is the tight regulation of ion
      channels expressed in interstitial cells of Cajal and smooth muscle. Interstitial
      cells of Cajal generate the slow wave and amplify neuronal signals; smooth muscle
      functions as the final effector organ. Recent advances in our understanding of
      the expression and mechano-regulation of these different subtypes of ion channels
      have allowed the development of hypotheses on how ion channels transduce a
      variety of inputs into electrical signals that directly or indirectly regulate
      gastrointestinal motor activity.

PMID- 14644009
TI  - Calcium channels in enteric neurons.
AB  - The enteric nervous system consists of two ganglionated neural networks within
      the gut wall that contain as many neurons as the spinal cord. Connections exist
      between the neurons in these two networks, enabling motility and secretion to be
      coordinated. It is becoming increasingly apparent that Ca(2+) movements across
      the cell membrane and between various intracellular compartments play a major
      role in the regulation of neuronal excitability and neurotransmitter release.

PMID- 14644010
TI  - CFTR pharmacology and its role in intestinal fluid secretion.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      activated Cl(-) channel expressed in epithelial cells in the airways, pancreas,
      intestine and other fluid-transporting tissues. Cystic fibrosis is caused by
      mutations in the CFTR, resulting in impaired Cl(-) transport and plasma membrane
      targeting. CFTR is expressed in the lumenal membrane of enterocytes, where it
      functions as the principal pathway for secretion of Cl(-) and fluid in
      enterotoxin-induced secretory diarrheas such as cholera. Small-molecule CFTR
      inhibitors reduce enterotoxin-induced intestinal fluid secretion in animal
      models. CFTR inhibition might also reduce intestinal fluid losses in cholera and
      possibly in other infectious and non-infectious diarrheas.

PMID- 14644011
TI  - Plasticity in serotonin control mechanisms in the gut.
AB  - 5-hydroxytryptamine (5-HT or serotonin) is a charged molecule and must be
      transported across biological membranes. Enzymes that catabolize 5-HT are all
      intracellular; therefore, 5-HT inactivation requires a high affinity transporter,
      known as serotonin transporter (SERT or 5-HTT). In the central and enteric
      nervous systems, SERT is located in serotonergic neurons; however, these neurons
      are not present in the gastrointestinal mucosa, where 5-HT initiates peristaltic
      and secretory reflexes. Instead, SERT is expressed by enterocytes. The severity
      of gastrointestinal effects caused by drugs that inhibit SERT, such as tricyclic
      antidepressants, selective serotonin reuptake inhibitors and cocaine, does not
      usually prevent their therapeutic or recreational use because backup transporters
      and alterations in receptor gene expression allow the gut to adapt, albeit
      imperfectly, to their toxicity.

PMID- 14644012
TI  - Role of ion channels in mechanisms controlling gastrointestinal pain pathways.
AB  - Hypersensitivity or sensitization of nociceptive primary afferents in the
      gastrointestinal tract has been proposed as a mechanism for organic and
      functional gastrointestinal pain. This hypersensitivity can be the result of
      alterations, either induced by a sensitizing agent or without a peripheral cause,
      in the functional properties of ion channels located in primary afferents. The
      tetrodotoxin-resistent sodium channel, known as Na(v)1.8, is present in
      nociceptive primary afferents, including those from the gut, and it has been
      implicated as being the main candidate for the enhanced activity that
      characterizes nociceptor sensitization. Other voltage-gated channels, such as
      calcium and potassium channels, can also contribute to the sensitization of
      primary afferents observed in gastrointestinal pain states.

PMID- 14644013
TI  - Excitability of nodose ganglion cells and their role in vago-vagal reflex control
      of gastrointestinal function.
AB  - A large body of evidence has demonstrated that vagal afferent neurones show non
      uniform properties and that distinct neuronal populations can be identified
      within the nodose ganglia. Of particular interest is recent work illustrating the
      significant degree of plasticity displayed by vagal sensory neurones; alterations
      in vagal afferent neuronal excitability might be important in the development and
      maintenance of gastrointestinal pathological states. Although it is unclear
      whether such adaptations are mimicked centrally, recent studies suggest that
      tonic afferent vagal inputs act as a 'brake' on inputs to the dorsal motor
      nucleus of the vagus. It would be reasonable to assume, therefore, that
      plasticity in the excitability of vagal afferent neurones would have dramatic
      consequences for the regulation and modulation of gastrointestinal vago-vagal
      reflexes.

PMID- 14644014
TI  - Acid-sensitive ion channels in gastrointestinal function.
AB  - Deviations from the physiological values of extracellular pH are monitored by
      multiple acid sensors. Acid-sensing ion channels are activated by moderate
      acidification, whereas transient receptor potential cation channels, notably
      TRPV1, are gated by severe acidosis. In contrast, ionotropic purinoceptor (P2X)
      ion channels, particularly P2X(2), and two-pore domain background K(+) channels,
      such as TASK, do not directly signal acidification but rather modulate cell
      membrane excitability in response to acidosis. These acid sensors, which are
      expressed by afferent neurons, are most relevant to the regulation of acid
      secretion, foregut motility and mucosal protection, as well as to
      gastrointestinal disturbances associated with inflammation, ischaemia and stasis.

PMID- 14644015
TI  - Estrogens in postmenopausal women: recent insights.
AB  - Recent literature has consistently supported the use of postmenopausal estrogens
      for treatment of moderate-to-severe vasomotor symptoms and for prevention of
      osteoporosis. Although assessment of quality of life is complex, symptom relief
      has often been shown to translate into improvements in quality of life measures
      for women. Recent studies have reported a small increase in breast cancer with
      long-term hormone therapy, as well as a small increase in cardiovascular events
      and dementia when therapy is started in a population that is, on average, 13
      years post-menopause. Ongoing investigations into different formulations and
      dosing options, as well as genetic factors that might influence the response to
      therapy, should provide valuable information.

PMID- 14644016
TI  - Clinical uses and misuses of dehydroepiandrosterone.
AB  - Dehydroepiandrosterone is the most abundant adrenal androgen and also functions
      as a neurosteroid. Serum concentrations decline with age and can serve as a
      prognostic factor in both critical illnesses and breast cancer progression.
      Evidence is accruing in support of dehydroepiandrosterone supplementation in
      adrenal insufficiency, hypopituitarism, osteoporosis, systemic lupus
      erythematosus, depression and schizophrenia. Research is ongoing at both the
      basic and the clinical level to elucidate mechanisms of action and establish
      efficacy and safety, as well as to expand new areas of potential application for
      this multi-faceted hormone.

PMID- 14644017
TI  - Adult growth hormone replacement: current understanding.
AB  - Initial studies of growth hormone (GH) replacement in adults used weight- and
      surface area-based dosing regimes extrapolated from paediatric practice. Much of
      the beneficial effects were pharmacological rather than physiological.
      Furthermore, weight-based dosing regimens resulted in lower overall doses in
      females who require approximately threefold greater GH secretion in health to
      maintain a similar insulin-like growth factor-I level to males. This inequality
      of dosing explains studies reporting that males respond more efficaciously to GH
      replacement. Recent studies individualising GH doses to normalize serum insulin
      like growth factor-I level have shown a similar spectra of beneficial effects to
      earlier weight-based studies; however, the degree of these effects on biological
      sequelea was reduced. Using this individualised dosing regimen, both genders
      responded equally to GH replacement for most biological end-points. The effect of
      GH replacement on bone mineral content is complex, and is dependent on the onset
      of GH deficiency, age of the patient and dosing regimen. GH is increasingly
      recognized as being intricately involved in regulation of surrogate markers of
      vascular risk and endothelial dysfunction, replacement of which normalises these
      indices. Definitive data on the effect of GH on mortality is awaited. Studies of
      5-10 years duration suggest that beneficial effects of GH are maintained long
      term. A depot preparation of GH is currently under investigation and, if proven
      to be efficacious and safe, might be a more acceptable therapy to a proportion of
      patients.

PMID- 14644018
TI  - The use of estrogen therapy in men.
AB  - Men make estrogen throughout their lives through the bioconversion of androgens
      by the aromatase enzyme in gonadal, as well as peripheral, tissues. The role of
      estrogen in men is not well understood; however, recent research interest has
      focused on this intriguing question. In some areas, such as the bone and
      cardiovascular systems, insights are beginning to be gained. Nevertheless, the
      clinical use of estrogen in men is limited.

PMID- 14644019
TI  - The clinical uses of leptin.
AB  - Leptin is the first of a group of adipocyte-secreted hormones to be used
      clinically to treat hypoleptinemic states. In children with congenital leptin
      deficiency and extreme obesity, leptin induces satiety and a dramatic loss of
      weight. In hypoleptinemic patients with extreme insulin resistance and
      lipodystrophy, leptin ameliorates insulin resistance, hyperglycemia,
      hyperinsulinemia, dyslipidemia and hepatic steatosis. In both these leptin
      deficient states, leptin therapy restores gonadotrophin secretion, as well as
      luteinizing hormone and thyroid-stimulating hormone pulsitility.

PMID- 14644020
TI  - Gonadotropin-releasing hormone antagonists.
AB  - Hypothalamic gonadotropin-releasing hormone (GnRH) is a decapeptide that
      stimulates pituitary synthesis and secretion of gonadotropins and, therefore,
      gonadal hormones. GnRH antagonists, of which thousands have been formulated,
      inhibit the hormone from binding to its receptor, inducing a pharmacological
      hypophysectomy. Peptide derivations of GnRH and non-peptide compounds are both in
      clinical trials or approved for assisted reproduction. As these compounds reach
      the market, the use of antagonists might expand to treatment of other hormonally
      dependent diseases, hormonal male contraception and growth inhibition of extra
      pituitary cancer cells expressing GnRH receptors.

PMID- 14644021
TI  - Status and future direction of male contraceptive development.
AB  - Control of fertility constitutes a global health issue, as overpopulation and
      unintended pregnancy have both major personal and societal impact. Although the
      contraceptive revolution in the 1960s following the development of hormonal-based
      oral contraceptives for women has had a major impact on societal dynamics in
      several cultures, little product innovation has occurred since then. One solution
      to this global health issue lies in the development of new and innovative
      contraceptives for both women and men, the goal of which is to provide a range of
      options for people at all stages and walks of life. Currently, three options for
      male-based contraception exist (i.e. withdrawal, condoms and vasectomy), and
      these are acknowledged as woefully inadequate. Introduction of new forms of male
      contraception based on both hormonal and non-hormonal paradigms are wanted and
      needed; this need is now becoming recognized by both the public and private
      sectors. New and innovative products will come from our knowledge of the unique
      physiology and genetics of reproduction, as well as by exploiting existing and
      future genomics, proteomics and protein network platforms.

PMID- 14644022
TI  - Medical treatment in acromegaly.
AB  - Acromegaly is a rare disabling disorder that results in premature death. The
      excess mortality and morbidity are the result of prolonged elevation of growth
      hormone (GH) and insulin-like growth factor-I (IGF-I) levels, and vigorous
      control of these improves well-being and restores life expectancy to normal.
      Recognition of the benefits of treatment has emphasised the need for optimal
      control of the GH/IGF-I axis. Transsphenoidal surgery is first-line therapy in
      the majority of patients; however, as most tumours are macroadenomas, cure rates
      are low. The role of radiotherapy is evolving and, although extremely effective
      at controlling tumour growth, it can take up to 15 years to control GH & IGF-I
      levels. In the interim, medical therapy is necessary. Dopamine agonists are
      inexpensive oral agents but, although most patients experience some benefit, GH
      and IGF-I levels are only normalised in around 35-40% of patients, and side
      effects are common. Somatostatin analogues are the gold standard of medical
      treatment. They can induce tumour shrinkage in a proportion of patients and can
      normalise the GH/IGF-I axis (at best) in approximately 65% of individuals;
      however, this leaves a significant cohort uncontrolled. The advent of the GH
      receptor antagonist pegvisomant provides the potential for IGF-I to be normalised
      in virtually every patient, but this novel form of therapy, which does not act on
      the pituitary, also raises many questions.

PMID- 14644023
TI  - Therapy for polycystic ovarian syndrome.
AB  - Polycystic ovarian syndrome is the most common endocrine disorder in women of
      reproductive age. Women with this disorder exhibit an array of disorders,
      including oligo-ovulation, hyperandrogenism, obesity, hyperlipidemia, infertility
      and insulin resistance. Of the sequelae that women experience, insulin resistance
      is associated with the most profound long-term morbidity. Initially, treatment
      regimens targeted specific symptomatology in these women, such as oligomenorrhea
      or hirsutism. With the discovery of the common association between insulin
      resistance and polycystic ovarian syndrome, however, we are able to utilize a new
      class of systemically targeted drugs that work on many of the symptoms found in
      these women.

PMID- 14644024
TI  - Vasopressin receptor antagonists in heart failure.
AB  - There is ample evidence that arginine vasopressin (AVP) is a component of the
      neurohormonal response to congestive heart failure (CHF). Furthermore, AVP might
      play a role in the development, progression and worsening of CHF. Because of the
      need for further improvement in the treatment of CHF, randomized clinical trials
      were conducted to assess the efficacy and safety of non-peptide AVP receptor
      antagonists in patients with CHF. In pivotal trials of three non-peptide AVP
      receptor antagonists, these compounds improved the fluid status, osmotic balance
      and hemodynamics of patients with CHF. These studies support the approval of this
      class of agents for the symptomatic treatment of CHF, but long-term studies are
      required to demonstrate their role in the outcome and quality of life of these
      patients.

PMID- 14644025
TI  - CD134 plays a crucial role in the pathogenesis of EAE and is upregulated in the
      CNS of patients with multiple sclerosis.
AB  - We investigated the role of the CD134 (also named OX40) molecule in experimental
      allergic encephalomyelitis (EAE) and multiple sclerosis (MS). We examined the
      susceptibility of Cd134(-/-) mice to EAE, an autoimmune murine model that is
      dependent on infiltrating CD4+ T lymphocytes reactive to myelin proteins. EAE
      induced by myelin oligodendrocyte glycoprotein (MOG) injection in Cd134(-/-) mice
      showed less severe clinical signs of disease and markedly reduced inflammatory
      infiltrates within the central nervous system (CNS). Resistance was associated
      with a strong reduction of pathogenic IFNgamma-producing T cells infiltrating the
      CNS of Cd134(-/-) mice. Furthermore, analysis of CNS tissue sections from EAE
      animals and MS patients revealed the presence of CD134+ cells that were localized
      in active lesions, mainly in perivascular infiltrates. The presence of CD134
      expressing T cells in brain tissue of MS patients and EAE affected mice, together
      with the functional evidence provided by the significant decrease in disease
      score obtained in Cd134(-/-) mice, indicate that interfering with the CD134
      molecule in T cells may be an appropriate target for therapeutic intervention in
      active MS.

PMID- 14644026
TI  - Amyloid-beta peptide-specific single chain Fv antibodies isolated from an immune
      phage display library.
AB  - A single-chain fragment variable (scFv) antibody library displayed on phage was
      constructed using spleen cells from mice immunized with human amyloid-beta
      peptide (Abeta42). This first anti-Abeta42 scFv immune antibody library was
      selected against human Abeta42. A number of positive clones were obtained, and
      sequences of VH and Vkappa genes were analyzed using ExPASy and BLAST computer
      tools. This analysis revealed that only two unique clones with identical VH and
      Vkappa complementarity determining region (CDR) (except HCDR2) and identical
      germline genes were selected, indicating that oligoclonal immune response was
      occurring in Abeta42-immunized mice. Abeta42-specific scFv antibodies selected
      from this first immune anti-Abeta42 phage antibody library may be an important
      tool for the development of therapeutic molecules for Alzheimer's disease (AD).

PMID- 14644027
TI  - Ultrastructural evidence of brain mast cell activation without degranulation in
      monkey experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is an animal model for the human
      demyelinating disease multiple sclerosis (MS). Increased permeability of the
      blood-brain barrier (BBB) precedes the development of clinical or pathologic
      findings in MS and may be induced by perivascular brain mast cells secreting
      vasoactive and proinflammatory molecules. Brain mast cells were investigated
      ultrastructurally in acute EAE of the non-human primate common marmoset
      Callithrix jacchus, which develops a mild neurologic relapsing-remitting course.
      Control diencephalic samples contained perivascular mast cells with mostly intact
      electron dense granules. In contrast, EAE samples had marked demyelination and
      mast cells with numerous altered secretory granules; their electron dense content
      varied in amount and texture with a "honeycomb" or "target" appearance, but
      without degranulation. These changes were evident even before the development of
      any clinical symptoms and suggest that brain mast cells may be involved in EAE,
      and possibly MS, through a unique process that may involve selective secretion of
      molecules able to disrupt the BBB.

PMID- 14644028
TI  - Chemokine-induced cell death in CCR5-expressing neuroblastoma cells.
AB  - CCR5 is expressed in neurons but its function in this cellular context is
      hitherto poorly understood. We have generated CCR5-expressing SH-SY5Y
      neuroblastoma cells. CCR5 ligands induced cell death in these cells, but not in
      control neuroblastoma cells or in CCR5-expressing fibroblasts. CCR5-dependent
      killing of neuroblastoma cells occurred through apoptosis, since it was
      accompanied by caspase-3 activation and could be prevented by a caspase-3
      inhibitor. Finally, cell killing by activated microglia was more rapid and
      extensive in CCR5-expressing neuroblastoma cells than in control cells. In
      summary, CCR5 may act as a death receptor in cells of neuronal lineage and
      therefore be involved in inflammatory neurodegeneration.

PMID- 14644029
TI  - Identification of a truncated IL-18R beta mRNA: a putative regulator of IL-18
      expressed in rat brain.
AB  - Interleukin (IL)-18, a member of the IL-1 family, is a key mediator of peripheral
      inflammation and host defense responses, and has been implicated in inflammatory
      and neurodegenerative diseases in the brain. IL-18 acts via a receptor complex
      that closely resembles that of IL-1, consisting of a ligand binding protein, IL
      18Ralpha, and an accessory protein, IL-18Rbeta. Here, we describe the presence of
      a splice variant of IL-18Rbeta that is predicted to encode a truncated soluble
      protein, consisting of only the first immunoglobulin-like domain of IL-18Rbeta
      (EMBL/Genbank accession number AJ550893). Both forms of IL-18Rbeta were expressed
      in rat cortex, striatum, hypothalamus, hippocampus, and also liver, and were
      detected in pure cultures of microglia, astrocytes and neurons. This novel splice
      variant is up-regulated rapidly in microglial cells by bacterial
      lipopolyssacharide (LPS). We propose that this putative truncated form of IL
      18Rbeta is analogous to the soluble form of IL-1R accessory protein, and could
      act as an important regulator of IL-18 actions.

PMID- 14644030
TI  - Cannabinoids and opioids share cAMP pathway in rat splenocytes.
AB  - In the present work we investigated on rat splenocytes long-term interactions
      between opioid and cannabinoid drugs in terms of a common regulation of cAMP
      intracellular pathway. Both morphine and the synthetic cannabinoid compound CP
      55,940 inhibited in a concentration-dependent manner the intracellular cAMP level
      in splenocytes stimulated by forskolin. The in vitro combination of submaximal
      concentrations of the two drugs did not yield any additive effect on the
      inhibition induced by the two drugs. In splenocytes taken from rats chronically
      treated with CP-55,940 (0.2 mg/kg i.p., twice a day for 4.5 days) or morphine (5
      mg/kg s.c., twice a day for 6.5 days) and in vitro exposed to either CP-55,940 or
      morphine, it was found a desensitisation and cross-desensitisation to the
      inhibitory effects on cAMP production induced by the two drugs. Binding
      experiments on the cannabinoid receptors level in spleen coronal sections after
      in vivo chronic administration of morphine, revealed that there was no changes in
      the binding of [H3]-CP-55,940. Thus, these results strengthen the hypothesis of
      cAMP as part of the common intracellular pathway shared by opiates and
      cannabinoids at immune cell level.

PMID- 14644031
TI  - Lung cancer-derived bombesin-like peptides down-regulate the generation and
      function of human dendritic cells.
AB  - Development of tumors is regulated by tumor-derived neuroendocrine factors,
      including bombesin-like peptides (BLP). We have evaluated neuroendocrine
      regulation of dendritic cell (DC) maturation and function by both tumor-derived
      and purified bombesin (BOM), neuromedin B (NMB), gastrin-releasing peptide (GRP),
      and a BOM antagonist D-Phe-bombesin (DPB). BOM, NMB and GRP dose-dependently
      inhibited maturation of DC assessed as down-regulation of CD40, CD80 and CD86
      expression on DC. BOM and GRP also inhibited interleukin-12 (IL-12) production by
      DC and their ability to activate T cells. DPB partly abrogated immunosuppressive
      effect of tumor cells on DC. These data are a first evidence for the role of BLP
      in the regulation of DC maturation and function, demonstrating that BLP inhibit
      DC maturation and longevity in the lung cancer microenvironment. This suggests a
      new mechanism of tumor escape and provides new targets for the
      immunopharmacological correction of immune effectors in cancer.

PMID- 14644032
TI  - A hierarchy of T cell receptor motifs determines responsiveness to the
      immunodominant epitope in experimental autoimmune myasthenia gravis.
AB  - The predominant murine T lymphocyte population responding to Talpha146-162, the
      immunodominant epitope in EAMG, expresses the TCRBV 6 gene segment. However,
      cells expressing other TCRBV gene segments also react with this peptide. In order
      to more precisely characterize the Talpha146-162-specific TCR repertoire, we
      isolated CD4high cells from peptide-immunized mice. The majority of CD4high cells
      utilized an acidic TCR beta chain CDR3 motif regardless of TCRBV gene usage.
      Analysis of T cell clones demonstrated a fourfold higher avidity of Vbeta6+ than
      non-Vbeta6 cells for Talpha146-162 indicating that a hierarchy of TCR motifs
      determines T cell responsiveness in EAMG.

PMID- 14644033
TI  - Via beta-adrenoceptors, stimulation of extrasplenic sympathetic nerve fibers
      inhibits lipopolysaccharide-induced TNF secretion in perfused rat spleen.
AB  - Using a spleen slice microsuperfusion technique in mice, we have previously
      characterized the role of norepinephrine (NE) and other neurotransmitters for
      sympathetic modulation of IL-6 and TNF secretion of splenic macrophages. Since
      experiments in spleen slices do not reflect the situation of an entire perfused
      organ, we investigated sympathetic modulation of lipopolysaccharide (LPS)-induced
      secretion of IL-6 and TNF in perfusion experiments of rat spleen. In an organ
      bath, perfusion was performed in explanted whole spleens, and catecholamines and
      cytokines were measured by HPLC and ELISA, respectively. Release of NE depended
      on stimulation frequency (maximum at 10 Hz). Apart from NE, perfusates also
      contained significant amounts of dopamine and epinephrine. Furthermore, perfusate
      epinephrine levels correlated positively with perfusate NE levels (RRank=0.750,
      p<0.001) but not with plasma epinephrine concentrations. This indicates that
      epinephrine is a conversion product of sympathetically released NE. Early
      electrical stimulation of extrasplenic splenic nerves, 20 min after
      administration of LPS, significantly inhibited TNF secretion. This electrically
      induced effect was abrogated by simultaneous administration of propranolol (10(
      6) M) but it was not influenced by administration of either an alpha1- or alpha2
      adrenergic antagonist. Late electrical stimulation of splenic nerves, 2.5 h after
      administration of LPS, did not change TNF secretion. Interestingly, no influence
      of early or late sympathetic nerve fiber stimulation on IL-6 secretion was
      observed. In conclusion, this is the first perfusion study of the entire spleen
      that demonstrates that early electrical stimulation of sympathetic splenic nerve
      fibers directly inhibits LPS-induced TNF secretion. This study corroborates the
      idea that splenic sympathetic nerves are able to inhibit important activators of
      the innate immune system when stimulation happens very early or even prior to
      their induction by LPS.

PMID- 14644034
TI  - Tissue expression of inducible nitric oxide synthase requires IFN-gamma
      production by infiltrating splenic T cells: more evidence for immunosuppression
      by nitric oxide.
AB  - The cause of increased severity of experimental allergic encephalomyelitis (EAE)
      in inducible nitric oxide synthase (iNOS)(-/-) or IFN-gamma(-/-) mice remains
      unclear. Transient chimeras were generated to examine the source of iNOS-inducing
      IFN-gamma in the central nervous system (CNS). IFNgamma(-/-) donor cells induced
      severe EAE but no iNOS expression in the CNS of wild-type recipients upon their
      immunization. By contrast, milder EAE, but strong iNOS expression was induced in
      immunized recipients of wild-type donor spleen cells. These results demonstrate
      that IFN-gamma secretion by infiltrating spleen cells is essential for iNOS
      expression during CNS inflammation. Furthermore, splenic NO is immunosuppressive.

PMID- 14644036
TI  - Clinical relapses of multiple sclerosis are associated with 'novel' valleys in
      natural killer cell functional activity.
AB  - Natural killer (NK) cells are implicated in the pathogenesis of multiple
      sclerosis (MS). Nine relapsing-remitting MS (RRMS) patients along with age, sex,
      and NK responder status matched controls were studied serially. Although the
      average NK cell functional activity (FA) was not significantly different between
      both groups, four clinical relapses in RRMS patients were associated with the
      development of 'novel' valleys in FA. These valleys are of greater depth and
      duration than cyclical valleys observed in both RRMS and controls, precede the
      onset of clinical attacks, and are observed in RRMS but not controls. In both
      RRMS and controls, cyclical peaks and valleys in FA are determined by the number
      of CD33+, CD3-CD56+, and to a lesser extent CD3+CD56+ cells capable of binding
      targets and inducing cell-mediated cytotoxicity (CMC). In contrast, 'novel'
      valleys in FA result from a reduction in the ability of CD3-CD56+ bound to
      targets to induce CMC. The results suggest that RRMS patients are at greater risk
      for clinical relapses during 'novel' valleys in FA. Furthermore, these valleys
      are the result of cells with a NK cell phenotype being unable to deliver a
      'lethal' hit to targets.

PMID- 14644035
TI  - Neurochemical sensitization associated with systemic administration of tumor
      necrosis factor-alpha: adjuvant action in combination with bovine serum albumin.
AB  - Tumor necrosis factor-alpha (TNF-alpha) provokes a time-dependent sensitization
      of brain monoamine activity, plasma corticosterone activity and sickness
      behavior, the latter being reminiscent of septic or anaphylactic shock. In this
      investigation, bovine serum albumin (BSA) elicited similar corticosterone and
      sickness profiles, whereas the monoamine changes were not observed. The
      sensitization elicited by mTNF-alpha plus BSA was markedly greater than that
      elicited by BSA alone. Carrier-free TNF-alpha promoted the sensitization of brain
      monoamine activity, but not sickness or corticosterone. It is suggested that mTNF
      alpha acts as an adjuvant to the anaphylactic actions elicited by BSA, but may
      provoke a sensitization of monoamine activity which is time-dependent and varies
      across brain regions.

PMID- 14644037
TI  - Phenotypes indicating cytolytic properties of Borrelia-specific interferon-gamma
      secreting cells in chronic Lyme neuroborreliosis.
AB  - The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are
      mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb
      specific secretion of interferon-gamma (IFN-gamma), which may be important for
      the elimination of Bb, but this may also cause tissue injury. In order to
      increase the understanding of the pathogenic mechanisms in chronic
      neuroborreliosis, we investigated which cell types that secrete IFN-gamma. Blood
      mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis
      chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the
      induced IFN-gamma-secreting cells were analyzed with three different approaches.
      Cells expressing CD8 or TCRgammadelta, which both have cytolytic properties, were
      the main phenotypes of IFN-gamma-secreting cells, indicating that tissue injury
      in chronic neuroborreliosis may be mediated by cytotoxic cells.

PMID- 14644038
TI  - Cytokines and chemokines in neuro-Behcet's disease compared to multiple sclerosis
      and other neurological diseases.
AB  - Cytokines and chemokines in cerebrospinal fluid (CSF) can have implications on
      the pathogenesis of neuro-Behcet's disease (NB). CSF and serum samples from 33
      patients with NB, 25 with multiple sclerosis (MS), 20 patients with infectious
      and/or inflammatory neurological diseases (IN) and 14 with other noninflammatory
      neurological diseases (NIN) were investigated by ELISA. In the CSF, CXCL10 levels
      were significantly higher in NB and IN than NIN and MS, whereas CXCL8 was
      increased in NB compared to NIN. CCL2 levels in MS CSF and sera were lower,
      whereas CXCL8 in MS sera was higher than the other groups. IL-12 was elevated in
      CSF of IN compared to NB and NIN and also in the CSF of MS compared to NIN. No
      difference was detected for IL-10 and IL-17. These results reflect that NB has a
      mediator pattern in resemblance with non-specific inflammations such as neuro
      infections compared to autoimmune disorders such as multiple sclerosis,
      suggesting that a currently unknown infection might be the trigger of a
      vasculitic process in the central nervous system (CNS).

PMID- 14644039
TI  - C-C chemokine receptor 2 gene polymorphism in Japanese patients with multiple
      sclerosis.
AB  - C-C chemokine receptor 2 (CCR2) is a receptor for chemoattractant protein-1 (MCP
      1) and associated with infiltrating lymphocytes in chronic active multiple
      sclerosis (MS) lesions. To study the role of CCR2 gene in the development of MS,
      we investigated the CCR2-64I polymorphism in 122 MS patients and 112 healthy
      controls in a Japanese population. We also analysed the influence of CCR2-64I
      polymorphism on the clinical course, age at disease onset, and severity. The
      distribution of the CCR2-64I allele was significantly different between patients
      and controls (p=0.0187), and the 64I/64I homozygote was significantly less common
      in MS than in control. Logistic analysis, adjusted for HLA-DRB1*1501-positivity,
      revealed negative association between the CCR2-64I and MS (p=0.0204). There were
      no significant associations between CCR2 polymorphism and the clinical features
      of MS. Our results indicate that the presence of CCR2-64I allele seems to provide
      protection against the development of MS.

PMID- 14644040
TI  - Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple
      sclerosis and acute neurological disorders.
AB  - Nogo-A is a protein associated with central nervous system (CNS) myelin thought
      to impair regenerative responses and to suppress sprouting and plastic changes of
      synaptic terminals. In this study, we report that serum IgM autoantibodies to the
      recombinant large N-terminal inhibitory domain of Nogo-A are a frequent finding
      in multiple sclerosis (MS) and acute inflammatory (IND) and non-inflammatory
      neurological diseases (OND), but not in neurodegenerative diseases (ND), systemic
      inflammatory disease and healthy controls. Furthermore, we demonstrate
      intrathecal production of anti-Nogo-A antibodies measured by increased IgG
      indices. Intrathecal anti-Nogo antibodies were significantly more frequent in
      patients with relapsing-remitting as compared to chronic progressive (CP) MS. We
      also found a highly significant negative correlation of these antibody responses
      with age indicating that they are more frequent in younger patients. We finally
      demonstrate that human anti-Nogo-A antibodies recognize native Nogo-A in brain
      extracts, oligodendrocytes and cells expressing human Nogo-A.

PMID- 14644041
TI  - Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial
      meningitis.
AB  - CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC
      chemokine that specifically acts on neutrophils. To obtain insight into the
      extent of local presence and action of CXCL5 during bacterial meningitis, we
      measured its concentrations in cerebrospinal fluid (CSF) of patients with culture
      proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32)
      and compared these results with levels of other CXC-chemokines, CXCL8-
      (interleukin-8) and CXCL1-related oncogene (growth-related oncogene (GRO)-alpha).
      Patients with bacterial meningitis had profoundly elevated CSF concentrations of
      all three chemokines. CXCL5 was not detectable in patients with aseptic
      meningitis or control subjects. CSF from patients with bacterial meningitis
      exerted chemotactic activity towards neutrophils, which was partially inhibited
      by neutralizing antibodies against CXCL5 and CXCL8, but not CXCL1. CSF from
      controls exerted minor chemotactic activity, which could be strongly enhanced by
      the addition of recombinant CXCL5, CXCL8 or CXCL1. During bacterial meningitis,
      CXCL5 is elevated in CSF, where it is involved in the recruitment of neutrophils
      to the central nervous system.

PMID- 14644043
TI  - Expression, purification and spectroscopic studies of full-length Kir3.1 channel
      C-terminus.
AB  - A polypeptide corresponding to the full-length C-terminal cytoplasmic domain of a
      G-protein-regulated inwardly rectifying potassium channel (Kir3.1) bearing a
      hexahistidine (His6) tag was produced by DNA recombinant overexpression
      techniques in Escherichia coli. This permitted the isolation of approximately 5
      mg of pure protein per liter of bacterial culture. Further purification by size
      exclusion chromatography (SEC) of the C-terminal domain revealed that it exists
      predominantly as a dimer. The secondary structure was estimated using circular
      dichroism measurements that indicated the presence of approximately 35% beta
      sheet and approximately 15% alpha-helix. G-protein betagamma subunits incubated
      with His-tagged Kir3.1 C-terminal domain, bound to immobilized metal affinity
      chromatography (IMAC) resin, copurified with the peak of specifically eluted
      recombinant protein. These observations demonstrate that full-length Kir3.1 C
      terminus can be purified in a stable conformation capable of binding proteins
      known to activate Kir3 channels and may contain elements involved in channel
      assembly.

PMID- 14644044
TI  - Members of the cystatin superfamily interact with MMP-9 and protect it from
      autolytic degradation without affecting its gelatinolytic activities.
AB  - Matrix metalloproteinases (MMPs), like other proteinases, can undergo autolytic
      degradation once activated in vivo. Whereas the activities of these enzymes are
      tightly regulated by tissue inhibitors of matrix metalloproteinases (TIMPs), it
      is not clear mechanistically how these enzymes are protected from autolysis in
      their active state. We previously reported that MMPs particularly MMP-9 and MMP-2
      interact with the serum glycoprotein fetuin-A [Arch. Biochem. Biophys. (1995)
      322, 250], a member of the cystatin superfamily. In the present analyses, we
      demonstrate that this interaction protects MMP-9 from autolytic degradation
      without interfering with its enzymatic activity, allowing it to efficiently
      digest gelatin. Our data demonstrate that MMP-9 binds to members of the cystatin
      family with K(diss) ranging from 25 to 58 nM for fetuin-A and 1.5-1.9 microM for
      cystatin C. The ability of fetuin-A to protect MMP-9 from autolysis requires a
      molar ratio of at least 8:1 (fetuin-A/MMP-9). More interestingly, our data show
      that the other members of the cystatin also have the ability to protect MMP-9
      from autolysis, provided they are in molar excess relative to MMP-9. Taken
      together, our data suggest that cystatins, particularly fetuin-A, in any cellular
      compartment including the circulatory system, efficiently protect MMP-9 and
      possibly other MMPs from autolysis. This mechanism ensures the digestion of the
      preferred substrate for MMP-9 without sacrificing the enzyme in the process.

PMID- 14644045
TI  - Molecular cloning of an epidermal growth factor-like toxin and two sodium channel
      toxins from the sea anemone Stichodactyla gigantea.
AB  - An epidermal growth factor (EGF)-like toxin (gigantoxin I) and two sodium channel
      toxins (gigantoxins II and III), previously isolated from the sea anemone
      Stichodactyla gigantea, were cloned for their cDNAs. The precursor protein of
      gigantoxin I is composed of a signal peptide, propart and mature peptide, similar
      to those of gigantoxins II and III, and is much simpler in structure than those
      of mammalian EGFs. In addition, gigantoxin I as well as gigantoxins II and III
      was demonstrated to be contained in nematocysts, suggesting that gigantoxin I
      functions as a toxin in S. gigantea.

PMID- 14644046
TI  - Structural characterization of a recombinant flagellar calcium-binding protein
      from Trypanosoma cruzi.
AB  - Calflagin are flagellar calcium-binding proteins belonging to the EF-hand super
      family described in several protozoa, including Trypanosoma cruzi. Evidences have
      shown that Ca(2+) may play an important regulatory role in trypanosomatid
      flagellar mobility. In these parasites, the response of the cell to variations of
      Ca(2+) levels is determined by a variety of calcium-modulated proteins. Starting
      from T. cruzi cDNA lambdagt11 library trypomastigote, a clone encoding a 29-kDa
      flagellar protein designated recombinant calflagin (rC29) was selected. rC29 is a
      calcium-acyl switch protein modified by the addition of myristate and palmitate
      at its amino terminal segment. In this work, unmyristoylated rC29 was expressed
      in Escherichia coli as an intein fusion protein and purified by affinity
      chromatography. Circular dichroism (CD) and fluorescence measurements showed
      conformational changes of rC29 due to Ca(2+) binding. The Ca(2+) binding
      constants were obtained by tryptophan intrinsic fluorescence spectroscopy.
      Fluorescence titration exhibited two classes of Ca(2+)-binding sites in the
      unmyristoylated rC29, which bind calcium with apparent association constant of
      K(a) of 3.3+/-0.5 (10(6)) and 1.9+/-0.2 (10(4)) M(-1). Experiment using 8
      anilinonaphthalene-1-sulfonic acid (ANS) as hydrophobic probe showed that the
      Ca(2+)-loaded form of rC29 contains exposed hydrophobic surfaces, thus suggesting
      that rC29 is probably functioning as a calcium sensor.

PMID- 14644047
TI  - Unfolding and refolding of porcine odorant binding protein in guanidinium
      hydrochloride: equilibrium studies at neutral pH.
AB  - Unfolding and refolding studies on porcine odorant binding protein (pOBP) have
      been performed at pH 7 in the presence of guanidinium hydrochloride (GdnHCl).
      Unfolding, monitored by following changes of protein fluorescence and circular
      dichroism (CD), was found to be a reversible process, in terms of recovered
      structure and function. The equilibrium transition data were fitted by a simple
      two-state sigmoidal function of denaturant concentration and the thermodynamic
      folding parameters, derived from the two techniques, were very similar (average
      values: C(1/2) approximately 2.4 M, m approximately 2 kcal mol(-1) M(-1),
      DeltaG(unf,w)(0) approximately 4.7 kcal mol(-1)). The transition was independent
      of protein concentration, indicating that only monomeric species are involved.
      Only a minor protective effect by the fluorescent ligand 1-amino-anthracene (AMA)
      against protein unfolding was detected, whereas dihydromyrcenol (DHM) stabilised
      the protein to a larger extent (DeltaC(1/2) approximately 0.5 M). Refolding was
      complete, when the protein, denatured with GdnHCl, was diluted with buffer. On
      the other hand, refolding by dialysis was largely prevented by concomitant
      aggregation. The present results on pOBP are compared with those on bovine OBP
      (bOBP) [Biochim. Biophys. Acta 1599 (2002) 90], where subunit folding is
      accompanied by domain swapping. We finally suggest that the generally observed
      two-state folding of many lipocalins is probably favoured by their beta-barrel
      topology.

PMID- 14644048
TI  - Characterization of the isozymes of pyruvate dehydrogenase phosphatase:
      implications for the regulation of pyruvate dehydrogenase activity.
AB  - The activity of mammalian pyruvate dehydrogenase complex (PDC) is regulated by a
      phosphorylation/dephosphorylation cycle. Dephosphorylation accompanied by
      activation is carried out by two genetically different isozymes of pyruvate
      dehydrogenase phosphatase, PDP1c and PDP2c. Here, we report data showing that
      PDP1c and PDP2c display marked biochemical differences. The activity of PDP1c
      strongly depends upon the simultaneous presence of calcium ions and the E2
      component of PDC. In contrast, the activity of PDP2c displays little, if any,
      dependence upon either calcium ions or E2. Furthermore, PDP2c does not
      appreciably bind to PDC under the conditions when PDP1c exists predominantly in
      the PDC-bound state. The stimulatory effect of E2 on PDP1c can be partially
      mimicked by a monomeric construct consisting of the inner lipoyl-bearing domain
      and the E1-binding domain of E2 component. This strongly suggests that the E2
      mediated activation of PDP1c largely reflects the effects of co-localization and
      mutual orientation of PDP1c and E1 component facilitated by their binding to E2.
      Both PDP1c and PDP2c can efficiently dephosphorylate all three phosphorylation
      sites located on the alpha chain of the E1 component. For PDC phosphorylated at a
      single site, the relative rates of dephosphorylation of individual sites are:
      2>site 3>site 1. Phosphorylation of sites 2 or 3 in addition to site 1 does not
      have a significant effect on the rates of dephosphorylation of individual sites
      by PDP1c, suggesting a random mechanism of dephosphorylation. In contrast, there
      is a significant decrease in the overall rate of dephosphorylation of pyruvate
      dehydrogenase by PDP2c under these conditions. This indicates that the mechanism
      of dephosphorylation of PDC phosphorylated at multiple sites by PDP2c is not
      purely random. These marked differences in the site-specificity displayed by
      PDP1c and PDP2c should be particularly important under conditions such as
      starvation and diabetes, which are associated with a great increase in
      phosphorylation of sites 2 and 3 of pyruvate dehydrogenase.

PMID- 14644049
TI  - 1H-NMR study of dynamics and thermodynamics of Cl- binding to ferric hemoglobin
      of a midge larva (Tokunagayusurika akamusi).
AB  - The functional properties of the Arg residue at the E10 helical position in
      myoglobin and hemoglobin lacking the highly conserved His residue at the E7
      position have received considerable interest as to the structure-function
      relationship of the oxygen-binding hemoproteins, because Arg E10 in such proteins
      has been shown to play similar roles to those His E7 plays in ordinary proteins.
      One of the components of hemoglobin from the larval hemolyph of Tokunagayusurika
      akamusi is also a naturally occurring E7 genetic variant with Ile E7 and Arg E10.
      This study demonstrated, for the first time, that the positively charged,
      elongated, and flexible side-chain of Arg E10 in T.akamusi hemoglobin contributes
      to stabilization of the coordination of biologically relevant Cl(-) to heme iron.
      Determination of the dynamics of the Cl(-) binding to T. akamusi ferric
      hemoglobin involving paramagnetic 1H-NMR indicated that the Cl(-) affinity
      increases with decreasing pH as a result of the fact that the binding rate
      increases with decreasing pH, whereas the dissociation rate is almost completely
      independent of pH. The pH-dependent character of the Cl(-) binding rate
      correlated well with the ionization state of heme peripheral side-chain
      propionate groups, which was clearly manifested in the pH-dependent shift changes
      of heme methyl proton signals, suggesting that negative charges of heme
      propionate groups constitute a kinetic barrier for Cl(-) entry into the heme
      pocket. These findings provide an insight into the pH-dependent ligand binding
      properties of T. akamusi hemoglobin.

PMID- 14644050
TI  - Re: Cultural norms versus state law in treating incest: a suggested model for
      Arab families, by K. Abu Baker and M. Dwairy.

PMID- 14644052
TI  - Re: trends in child maltreatment literature (Behl, Conyngham, & May, 2003).

PMID- 14644054
TI  - Treating child abuse-related posttraumatic stress and comorbid substance abuse in
      adolescents.
AB  - OBJECTIVE: Child abuse is a risk factor for developing Posttraumatic Stress
      Disorder (PTSD) and subsequent Substance Use Disorder (SUD). The purpose of this
      review is to summarize current knowledge about effective treatments for
      adolescent abuse-related PTSD, SUD, and the co-occurrence of these conditions.
      METHOD: The literature on empirical treatment studies for these conditions in
      adolescence was reviewed, summarized, and synthesized. RESULTS: Randomized
      controlled studies of abuse-related PTSD and SUD in adolescents have supported
      the efficacy of cognitive behaviorally-based individual and family treatment
      components. Components overlap considerably in empirically supported treatments
      for each disorder. An integrated treatment approach is described for use in
      adolescents with abuse-related PTSD and SUD, with recommendations for optimizing
      services for this population and for future research. CONCLUSIONS: The available
      evidence on effective treatments suggests that integrated PTSD- and SUD-focused
      cognitive-behavioral and family treatment for adolescents with comorbid abuse
      related PTSD and SUD may optimize outcomes for this population.

PMID- 14644055
TI  - Violence among family members of children and adolescents evaluated for sexual
      abuse.
AB  - OBJECTIVES: The two aims of this study were to: (1). describe the prevalence and
      characteristics of domestic adult and child physical violence in the homes of
      children and adolescents evaluated in a specialized sexual abuse clinic and (2).
      describe parent or caretaker responses to domestic adult and child violence and
      child sexual abuse, including tendencies to report or seek medical care. METHOD:
      A consecutive sample of 164 subjects (ages 7-19) were interviewed in a sexual
      abuse clinic regarding in-home violent or abusive experiences among family
      members that had occurred at any time during their childhood. RESULTS: Fifty-two
      percent of these children and teenagers reported spousal violence in their home.
      Fifty-eight percent of child sexual offenders who were in-home males also
      physically abused their adult female partner. Half of in-home males who were
      physically violent to children also sexually abused them. In 86% of homes with
      partner violence, the children were also physically assaulted. There was no
      difference in sexual abuse disclosure rates or patterns for children living with
      or without adult violence. CONCLUSIONS: Sexually abused children should be
      questioned about physical abuse and the presence of violence among adults in
      their home. Safety plans for sexually abused children should incorporate
      screening for family violence and safety plans for parents and siblings of child
      victims, when appropriate.

PMID- 14644056
TI  - The role of social support in well-being and coping with self-reported stressful
      events in adolescents.
AB  - OBJECTIVE: This study investigated the role that social support plays in well
      being and in coping after a stressful event in a group of non-clinical
      adolescents. Furthermore, this study aimed at replicating the finding that
      adolescents who reported sexual abuse reported more symptoms and less adequate
      coping strategies than adolescents who reported another type of stressful event
      or no stressful episode. METHOD: Eight hundred and twenty adolescents between 12
      and 18 years of age filled out questionnaires assessing social support (Social
      Support Questionnaire, Sarason, Shearin, Pierce, & Sarason, 1987), trauma-related
      symptoms (Trauma Symptom Checklist for Children, Briere, 1996), behavior problems
      (Youth Self-Report, Achenbach, 1991), and coping (How I Cope Under Pressure
      Scale, Ayers, Sandler, West, & Roosa, 1996). RESULTS: 42% of the adolescents
      reported a stressful experience, and 4.4% reported sexual abuse. Sexually abused
      adolescents reported more stress-related symptoms and used more avoidance and
      fewer support-seeking coping strategies than the other adolescents. The main
      effect hypothesis of social support was sustained, but social support did not
      moderate the relation between a stressful event and coping. Yet, a trend was
      found suggesting that high support from the family was associated with less
      avoidance coping and more support-seeking in adolescents who reported a non
      sexually abusive, stressful event. CONCLUSIONS: Our findings show that a highly
      perceived availability of social support is directly associated with fewer trauma
      related symptoms, especially in adolescents who are non-sexually abused. For
      adolescents who reported a sexual or another type of stressful event, social
      support did not play a different role in coping.

PMID- 14644057
TI  - Reported contact with child protection services among those reporting child
      physical and sexual abuse: results from a community survey.
AB  - OBJECTIVE: This study uses results from a large community survey to examine the
      relationship between a history of child maltreatment and self-reports of contact
      with Child Protection Services (CPS). METHODS: The Ontario Health Supplement was
      a province-wide, probability-based survey of household dwellings in the province
      of Ontario, Canada. A random sample of residents aged 15 and older participated
      in the Ontario Health Supplement (N=9953). A face-to-face interview included a
      question about contact with Child Protection Services (CPS), and the Child
      Maltreatment History Self-Report, a self-administered questionnaire, was used to
      assess history of child physical and sexual abuse. RESULTS: Only a very small
      percentage of respondents with a history of child abuse reported contact with
      CPS; 5.1% of those with a history of physical abuse, and 8.7% of those with a
      history of sexual abuse. Contact with CPS was associated with younger age of
      respondent for both types of abuse and female gender for physical abuse. In the
      case of sexual abuse, younger respondents whose parental employment
      classification was in the lower socioeconomic group were more likely to have
      contact with CPS. CONCLUSIONS: Interventions that target only those who come in
      contact with CPS will not reach most persons exposed to child abuse.

PMID- 14644058
TI  - The relationship between parental substance abuse and child maltreatment:
      findings from the Ontario Health Supplement.
AB  - OBJECTIVE: This study examined the relationship between reported exposure to
      child abuse and a history of parental substance abuse (alcohol and drugs) in a
      community sample in Ontario, Canada. METHOD: The sample consisted of 8472
      respondents to the Ontario Mental Health Supplement (OHSUP), a comprehensive
      population survey of mental health. The association of self-reported
      retrospective childhood physical and sexual abuse and parental histories of drug
      or alcohol abuse was examined. RESULTS: Rates of physical and sexual abuse were
      significantly higher, with a more than twofold increased risk among those
      reporting parental substance abuse histories. The rates were not significantly
      different between type or severity of abuse. Successively increasing rates of
      abuse were found for those respondents who reported that their fathers, mothers
      or both parents had substance abuse problems; this risk was significantly
      elevated for both parents compared to father only with substance abuse problem.
      CONCLUSIONS: Parental substance abuse is associated with a more than twofold
      increase in the risk of exposure to both childhood physical and sexual abuse.
      While the mechanism for this association remains unclear, agencies involved in
      child protection or in treatment of parents with substance abuse problems must be
      cognizant of this relationship and focus on the development of interventions to
      serve these families.

PMID- 14644059
TI  - Major findings from the Canadian incidence study of reported child abuse and
      neglect.
AB  - OBJECTIVE: To present key findings from the Canadian Incidence Study of Reported
      Child Maltreatment (CIS) in sufficient detail to provide a basis for
      international comparisons in terms of forms and severity of maltreatment and the
      age and sex of victims. METHOD: A survey conducted in a random sample of 51 child
      welfare service areas across Canada tracked child maltreatment investigations
      conducted during the months of October to December 1998, produced a national
      sample of 7672 child maltreatment investigations. Information was collected
      directly from investigating workers on child and family background, perpetrator
      characteristics, severity and types of maltreatment and service and court
      outcomes of investigations. RESULTS: Forty-five percent of investigations were
      substantiated and in a further 22% of investigations maltreatment remained
      suspected. Primary reasons for investigation were physical abuse (31%), sexual
      abuse (11%), neglect (40%), and emotional maltreatment (19%). A larger proportion
      of physical abuse cases are isolated incidents involving older children and are
      more likely to lead to injuries. Sexual abuse, neglect and emotional maltreatment
      involve more chronic situations with children showing signs of emotional harm.
      Rates of investigated and substantiated maltreatment are lower in Canada compared
      to the United States, but are higher than rates reported in Australia.
      CONCLUSIONS: The CIS provides much needed information for developing a better
      understanding of the profile and needs of children and families investigated by
      child welfare authorities in Canada. The study also serves as a point from which
      international comparisons can be made.

PMID- 14644063
TI  - Peripheral selectivity and apparent efficacy of dynorphins: comparison to non
      peptidic kappa-opioid agonists in rhesus monkeys.
AB  - The potency and effectiveness of dynorphin A(1-17), E-2078 (a synthetic dynorphin
      A(1-8) analog) and non-peptidic kappa-opioid agonists were studied in rhesus
      monkeys in two assays: 1) a drug discrimination assay with the centrally
      penetrating kappa-agonist U69,593 as the training stimulus (n=3) and 2) a
      prolactin release assay; a neuroendocrine effect thought to be mediated by kappa
      receptors located in hypothalamic nuclei outside the blood-brain barrier. The non
      peptidic kappa-agonists, U69,593 and bremazocine (0.00032-0.01 mg/kg, s.c.) were
      dose-dependently generalized by all the subjects trained to discriminate U69,593.
      U69,593 and bremazocine also caused dose-dependent prolactin release (n=4). By
      contrast, dynorphin A(1-17) and E-2078 (0.1-1 mg/kg, i.v.) were only generalized
      by one of the U69,593 discriminating subjects. However, both these dynorphins
      produced potent and robust prolactin release (0.0032-0.032 mg/kg, i.v.), when
      tested under an identical time course design as above. Naltrexone (0.1 or 0.32
      mg/kg), caused a parallel rightward shift in the dose-effect curves for all the
      above ligands, consistent with kappa-receptor mediation of this neuroendocrine
      effect. The peripherally selective antagonist, quaternary naltrexone (0.32 mg/kg,
      s.c.) partially blocked the neuroendocrine effects of U69,593 and E-2078 (0.0032
      mg/kg, s.c. and i.v., respectively). Overall, these findings are consistent with
      the hypothesis that the dynorphins act as high efficacy, peripherally selective
      kappa-agonists following systemic administration in primates.

PMID- 14644064
TI  - Free recall of pleasant words from recency positions is especially sensitive to
      acute administration of cortisol.
AB  - In a recent study we investigated the acute effects of cortisol administration in
      healthy male volunteers on free recall of pleasant, unpleasant, and neutral nouns
      using a between-subjects double-blind placebo-controlled design. The volunteers
      were administered 10 mg of hydrocortisone or placebo between 9:00 and 10:30. Two
      hours after administration of cortisol a decline in recall of neutral and
      pleasant words was found, while recall of unpleasant words did not change. These
      results are consistent with a possible inhibitory influence of cortisol on a
      prefrontal dopaminergic mechanism involved in approach and positivity bias. In
      this paper we first explain why this interpretation would predict recall of
      pleasant words from recency positions to be especially sensitive to cortisol
      administration. Comparing primacy and recency recall of pleasant and unpleasant
      words, there proved to be a selective decline in recall of pleasant recency
      words. These results did not appear to stem from differences in recall strategies
      between our groups of volunteers.

PMID- 14644065
TI  - Administration of progesterone produces mild sedative-like effects in men and
      women.
AB  - The goal of this study was to investigate the behavioral and subjective effects
      of a single dose of progesterone in men and women. Certain metabolites of
      progesterone (e.g., allopregnanolone) are potent positive allosteric modulators
      of GABA(A) receptors, and produce sedative-like effects in laboratory animals.
      This study was designed to examine the acute effects of these neurosteroids in
      humans. Women (n=7) in their early follicular phase and men (n=10) received
      intramuscular injections of progesterone (200 mg) or placebo. Dependent measures
      included plasma levels of progesterone and allopregnanolone, self-report measures
      of mood and subjective effects and behavioral measures of psychomotor
      performance. Plasma concentrations of progesterone and allopregnanolone increased
      reliably and with little intersubject variability after drug administration, and
      levels were similar in men and women. Administration of progesterone produced
      small, delayed increases in heart rate and feelings of fatigue, and it impaired
      smooth eye pursuit. These results suggest that, although the effects are modest
      and not simply related to plasma concentrations, progesterone and its metabolites
      can produce sedative-like effects in both men and women.

PMID- 14644066
TI  - Diurnal cycles of salivary cortisol in older adults.
AB  - Cortisol has a well-documented circadian pattern. However, recent studies have
      demonstrated that individual variation in diurnal cortisol patterns occurs in
      young adult populations. Since older adults experience altered sleep-wake cycles
      and changes in circadian rhythmicity, we may see even greater variations in
      diurnal cortisol patterns in older adults. This study examined salivary cortisol
      patterns in 48 community dwelling older adults. Participants (mean age 76+/-6)
      collected saliva every 2 h over a three-day period. Cortisol was assayed by using
      RIA. Cortisol cycles were defined as inconsistent, typical or flat based on the
      slopes of two sequential daily cortisol patterns. Demographic, physical,
      psychological and behavioral measures were tested for group differences using t
      tests and chi-square analyses. Forty-eight percent of the sample had inconsistent
      cycles, 50% had typical cycles and 2% had flat cycles. This sample had a higher
      percentage of inconsistent cycles and fewer flat cycles than reported for young
      adults (p=0.008) (Psychoneuroendocrinology 22 (1997) 89). Those with inconsistent
      cycles were younger and reported higher caffeine and food intake than those with
      typical cycles. This study demonstrates that normal diurnal rhythms of cortisol
      can be maintained in older adults, while day-to-day variation may increase.

PMID- 14644067
TI  - Comparison of HPA axis hormonal responses to naloxone vs psychologically-induced
      stress.
AB  - Although the naloxone challenge has been used to draw inferences about the
      dynamics of the stress response, this procedure has never actually been compared
      "head to head" with a psychological stressor. In the present study, we asked 14
      healthy volunteers to complete the naloxone challenge and the Trier Social Stress
      Test in an outpatient GCRC laboratory setting so that the degree of
      correspondence between the two procedures could be examined. Findings indicated
      that subjects who had greater ACTH responses to naloxone also had greater ACTH
      responses to the psychologically-induced stressor. This was true for both ACTH
      peak (r=0.57; p<0.04) and ACTH AUC response (r=0.64; p<0.02) measures; none of
      the cortisol summary score measures correlated significantly across the two
      challenges. Associations were also found between subjects' baseline personality
      characteristics and their ACTH responses to each of the challenges. Furthermore,
      the kinds of characteristics that predicted greater ACTH response to the
      pharmacological challenge were similar to the kinds of characteristics that
      predicted ACTH response to the psychological challenge. In general, higher scores
      on the NEO dimensions of Extraversion and Openness predicted greater ACTH
      responses. These findings give preliminary evidence that novelty-seeking behavior
      may be associated with HPA axis lability. The commonalities in personality
      predictors between the two challenges further support the notion that a common
      biological substrate may be, at least partially, responsible for the similarities
      in responses. However, caution should be used in assuming that responses to
      naloxone directly parallel responses to physiological stress.

PMID- 14644068
TI  - Effects of trauma exposure on the cortisol response to dexamethasone
      administration in PTSD and major depressive disorder.
AB  - OBJECTIVE: To evaluate cortisol suppression following 0.5 mg of dexamethasone
      (DEX) in trauma survivors (N=52) with posttraumatic stress disorder (PTSD), major
      depressive disorder (MDD), both, or neither disorder, and in subjects never
      exposed to trauma (N=10), in order to examine interactions between diagnosis and
      trauma history on cortisol negative feedback inhibition. METHOD: Lifetime trauma
      exposure and psychiatric diagnoses were assessed and blood samples were obtained
      at 8:00 a.m. for the determination of baseline cortisol. Participants ingested
      0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and
      DEX were obtained at 8:00 a.m. the following day. RESULTS: PTSD was associated
      with enhanced cortisol suppression in response to DEX. Among trauma survivors,
      the presence of a traumatic event prior to the "focal" trauma had a substantial
      impact on cortisol suppression in subjects with MDD. Such subjects were more
      likely to show cortisol alterations similar to those associated with PTSD,
      whereas subjects with MDD with no prior trauma were more likely to show
      alterations in the opposite direction, i.e. relative non-suppression.
      CONCLUSIONS: Cortisol hypersuppression in PTSD appears not to be dependent on the
      presence of traumatic events prior to the focal trauma. However, prior trauma
      exposure may affect cortisol suppression in MDD. This finding may have
      implications for understanding why only some depressed patients show non
      suppression on the DST.

PMID- 14644069
TI  - Serum levels of estradiol and testosterone and performance in different cognitive
      domains in healthy elderly men and women.
AB  - Sex hormones could protect against age-related cognitive decline in elderly men
      and women. We investigated the relationships between serum total testosterone
      (TT), total estradiol (TE2) levels and cognitive function in 145 non-demented
      elderly volunteers (aged 61-91 years) who were not using hormone replacement
      therapy (HRT). Women (n=66) were better at verbal recall than men (n=79) and men
      were slightly better at naming. There was a positive relationship between serum
      levels of TE2 and verbal list recall but not with other verbal memory tests (e.g.
      Verbal Paired Associates) in women. There was a negative relationship of serum TT
      levels with verbal recall. Surprisingly, women who were in the upper age tertile
      (> 77 years of age) were better at verbal recall than men and than women younger
      than 72; this effect was independent of hormone levels. Men between 61 and 72
      years of age showed a positive relationship between high TE2 levels and Spatial
      Span performance and between high TT levels and speed of information processing,
      while for women of this age-group, a negative relationship was found. These
      preliminary results were unchanged when controlling for education, sex hormone
      binding globulin levels, body mass index, depression, daily alcohol use and
      smoking. In sum, not all cognitive functions were better with higher levels of
      sex steroids and effects seemed to be modified by sex; the sex-sensitive tests
      showing the clearest effects. More research is required to investigate whether
      there is a window of time in which hormone therapy could be beneficial for middle
      aged men.

PMID- 14644071
TI  - Treatment and management of acute venous thromboembolic disease.
AB  - Venous thromboembolic (VTE) disease consists of deep vein thrombosis and/or
      pulmonary embolism. Either low molecular weight heparin given subcutaneously or
      unfractionated heparin administered intravenously are used for the initial
      treatment. Simultaneously, warfarin therapy is initiated. Thrombolytic therapy
      plays a limited role. Following the initial heparin treatment, anticoagulation
      clinics provide an excellent means of monitoring the oral anticoagulation.
      Patient education is important and patients should be well versed in the basic
      features of oral anticoagulation. The duration of oral anticoagulation is
      dependent on a number of factors including the presence of inherited risk
      factors, bleeding risk and patient reliability. Residual thrombus in the affected
      vein may indicate the need for prolonged anticoagulation. The low intensity oral
      anticoagulation (INR 1.5-2.0) is useful in preventing recurrent thrombosis
      following the initial treatment period with full intensity oral anticoagulation.

PMID- 14644072
TI  - Marine n-3 fatty acids and thrombosis.

PMID- 14644073
TI  - Fish oil inhibits photochemically induced thrombosis in the guinea pig in a dose
      dependent manner.
AB  - The dose-response effect of dietary fish oil was investigated in the
      photochemically induced thrombosis model in guinea pigs. In this arterial
      thrombosis model thrombus formation was evaluated by determination of different
      occlusion parameters (percentage of occlusion, area under the blood flow curve,
      time to first occlusion, spontaneous reflow). Sixty guinea pigs (7 weeks old)
      were randomly assigned to and fed a 40 energy % diet containing increasing
      amounts (0, 5.5, 17 and 36 energy %) of fish oil for four weeks. Arterial
      thrombosis was induced in the femoral artery by free radical damage and
      subsequent thrombus formation. Increasing fish oil concentrations in the diet
      were associated with a linear decrease (p<0.001) in the percentage of occlusion
      (calculated as a decrease in blood flow) and a linear increase in area under the
      blood flow curve/begin flow (p<0.001). The time to thrombus formation was not
      significantly prolonged in any group. However the frequency of animals in which
      complete occlusion of the femoral artery was not obtained during the thrombosis
      induction and subsequent observation period was higher in the groups receiving
      the two highest doses of fish oil. Spontaneous reflow correlated positively
      (p<0.013) with increasing dietary fish oil content. In conclusion, our data
      indicates that dietary fish oil inhibits photochemically induced thrombosis in
      this animal model of arterial thrombosis in a dose dependent manner.

PMID- 14644074
TI  - Reduced thrombus cohesion in an ex vivo human model of arterial thrombosis
      induced by clopidogrel treatment: kinetics of the effect and influence of single
      and double loading-dose regimens.
AB  - OBJECTIVE: To compare the effects of clopidogrel on ex vivo thrombogenesis with
      those on ADP-dependent platelet aggregation, and to compare single and double
      loading-dose regimens. METHODS AND RESULTS: Step 1: Volunteers (n=12) received
      clopidogrel 75 mg/day for 8 days. ADP-induced platelet aggregation was measured
      in platelet-rich plasma (PRP). Thrombogenesis was measured in an ex vivo model.
      Clopidogrel produced rapid platelet inhibition, increasing up to day 5. Maximal
      intensity of platelet aggregation correlated with density of platelet thrombus,
      surface of collagen covered by platelets and thrombus cross-sectional surface
      (p<0.001). Step 2: On day 1, volunteers (n=60) randomly received clopidogrel 75
      mg, a single 300-mg loading dose or two 300-mg loading doses separated by a 12-h
      interval. On day 2, all volunteers received clopidogrel 75 mg. Both loading dose
      regimens enhanced platelet inhibition at all time points (p<0.03 vs. clopidogrel
      75 mg). After 3 h, the antiplatelet effect of a loading dose was substantial, and
      the mean decrease in dense thrombus surface was greater in the loading-dose
      groups than in the 75 mg group (p=0.041 for the single loading dose). Ex vivo,
      there were no significant differences between loading-dose groups. CONCLUSIONS:
      Clopidogrel reduces arterial thrombus cohesion by an effect that correlates with
      inhibition of ADP-induced platelet aggregation. A single 300-mg loading dose
      provides a rapid onset of such an antithrombotic effect, which was more
      significant at 24 h with the double loading dose.

PMID- 14644075
TI  - Does the anti-beta2-glycoprotein I antibody provide additional information in
      patients with thrombosis?
AB  - OBJECTIVE: To investigate whether the anti-beta(2)-glycoprotein I (anti
      beta(2)GPI) antibody may provide additional information in patients with
      thrombosis in conjunction with the lupus anticoagulant (LAC) or anticardiolipin
      (aCL) antibody. METHODS: We selected 235 patients whose plasma were tested for
      the presence of all three antiphospholipid (aPL) antibodies (LAC, aCL, and anti
      beta(2)GPI) and were positive for at least one aPL antibody from January 2000 to
      December 2001. The LAC test was performed using dilute activated thromboplastin
      time reagent (dAPTT) and dilute Russell viper venom time reagent (dRVVT). ACL
      (IgG/IgM) and anti-beta(2)GPI (IgG/IgM) were detected by enzyme-linked
      immunosorbent assay (ELISA). Clinical data were collected and analysed in all
      patients with aPL antibody. RESULTS: Of the 235 patients with aPL, thrombosis was
      detected in 76 patients (28.0%). Of the 76 patients with thrombosis, 29 were
      positive for LAC, 9 for aCL, 7 for anti-beta(2)GPI, 3 for LAC+aCL, 9 for aCL+anti
      beta(2)GPI, 11 for LAC+anti-beta(2)GPI, and 8 for LAC+aCL+anti-beta(2)GPI. The
      rate of thrombosis was significantly different (p=0.01) among single positive
      patients (45/163, 27.6%), double positive patients (23/60, 38.3%), and triple
      positive patients (8/12, 66.7%). In single positive patients, the rate of
      thrombosis was highest in LAC positive patients (29/85, 34.1%). In double
      positive patients, the LAC+anti-beta(2)GPI positive group (11/24, 45.8%) and
      aCL+anti-beta(2)GPI positive group (9/22, 40.9%) had higher rates of thrombosis
      than the LAC+aCL positive group (3/14, 21.4%). CONCLUSION: Single positivity for
      anti-beta(2)GPI explained 9.2% of thrombotic events in the absence of LAC or aCL.
      Double or triple positivity for aPLs were associated with a higher rate of
      thrombosis than single positivity for aPL. Our results suggest that anti
      beta(2)GPI provides additional information in patients with thrombosis in
      conjunction with LAC or aCL.

PMID- 14644076
TI  - ADAMTS-13 activity in patients with brain and prostate tumors is mildly reduced,
      but not correlated to stage of malignancy and metastasis.
AB  - Impaired Von Willebrand factor cleaving activity of ADAMTS-13 was demonstrated in
      patients with metastasizing and malignant tumors. To investigate the relevance of
      ADAMTS-13 for tumor progression, we determined ADAMTS-13 activity and VWF:Ag in
      80 patients with various malignancies: 30 patients with benign brain tumors, 30
      patients with malignant brain tumors, 10 patients with local prostate tumors and
      10 patients with metastatic prostate tumors. We found mild ADAMTS-13 deficiency
      in 17/80 tumor patients, but there was no significant difference in ADAMTS-13
      activity between the age- and sex-matched patients with benign and malignant
      brain tumors nor between the age matched patients with local and metastatic
      prostate tumors. Patients with malignant brain tumors could only be distinguished
      from patients with benign tumors by elevated levels of VWF:Ag (p=0.018). Our data
      are hence in variance to previous studies, which found a distinct inverse
      correlation between ADAMTS-13 activity and level of metastasis and/or malignancy
      in diverse cancer-types.

PMID- 14644077
TI  - Homozygous C677T mutation in the MTHFR gene as an independent risk factor for
      multiple small-artery occlusions.
AB  - INTRODUCTION: Hyperhomocysteinemia is an independent risk factor for
      cerebrovascular disease and the homozygous C677T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene can induce hyperhomocysteinemia.
      However, the association between this 677TT genotype and ischemic stroke still
      remains controversial. Therefore, we carried out this study to determine whether
      the MTHFR TT genotype is associated with certain subtypes of ischemic stroke.
      MATERIALS AND METHODS: We enrolled 195 ischemic stroke patients and 198 healthy
      individuals and checked their fasting plasma homocysteine levels and analyzed the
      C677T polymorphism in the MTHFR gene. RESULTS: Our findings concur with previous
      reports that stroke occurrence is associated with hyperhomocysteinemia, but not
      with the 677TT genotype. However, when we re-analyzed the data based on a subtype
      classification, the adjusted odds ratio (AOR) and 95% confidence intervals (CI)
      of the 677TT genotype were found to be significantly higher in patients with
      small-artery occlusion than that in controls (AOR, 2.92; 95% CI, 1.01-8.48).
      Moreover, the AOR of the 677TT genotype was found to be much bigger in patients
      with multiple small-artery occlusions (AOR, 6.90; 95% CI, 1.70-27.99), but not in
      those with single small-artery occlusion (AOR, 1.19; 95% CI, 0.27-5.35).
      CONCLUSIONS: The homozygous C677T mutation in the MTHFR gene is associated with
      multiple small-artery occlusions, but not with single small-artery occlusion. Our
      findings suggest a genetic basis for certain subtypes of ischemic stroke.

PMID- 14644078
TI  - Parental history of hypertension is associated with coagulation-fibrinolytic
      balance disorders.
AB  - It has been previously shown that essential hypertension (EH) is associated with
      coagulation-fibrinolytic balance disorders. Our study was conducted in order to
      investigate disturbances in coagulation-fibrinolysis in offsprings of
      hypertensive parents. Two groups were studied: 44 healthy normotensive
      individuals (17 male, 27 female, age range 12-22 years) with a documented family
      history of hypertension and 33 individuals (14 male, 19 female, age range 11-21
      years) without a family history of essential hypertension. The following
      parameters were determined in both groups: plasminogen activator inhibitor-1
      antigen, tissue plasminogen activator antigen, fibrinogen, fibrin degradation
      products, thrombomodulin, protein S antigen, protein C activity, von Willebrand
      factor Ag, factor VII and factor XII activity. Additionally, systolic and
      diastolic blood pressure, insulin levels, blood lipids and heart rate were
      determined. The two groups were not found to have differences with respect to
      age, gender, body mass index, blood lipids and insulin levels. Hypertensive
      offsprings had significantly higher plasma levels of plasminogen activator
      inhibitor-1 antigen, fibrinogen, fibrin degradation products, protein S antigen
      and factor XII activity, while no differences were observed to the other
      haemostatic variables studied. Hence, offsprings of hypertensives had
      significantly higher diastolic blood pressure and heart rate. In conclusion,
      alterations regarding blood pressure, heart rate and fibrinolytic function exist
      in offsprings of hypertensive parents compared to individuals without family
      history of hypertension.

PMID- 14644079
TI  - Persistent high factor VIII:C in a child with ischemic stroke.

PMID- 14644080
TI  - Serum homocysteine and the severity of coronary artery disease.

PMID- 14644081
TI  - Differential effects of sodium nitroprusside and hydralazine in a rat model of
      topical FeCl3-induced carotid artery thrombosis.
AB  - INTRODUCTION: In the rat model of topical ferric chloride-induced carotid artery
      thrombosis, a transient blood flow velocity (VEL) increase is observed
      immediately following ferric chloride application. The immediacy of the response
      suggested vasoconstriction, as thrombotic narrowing of the vessel lumen was
      hypothesized to be too slow to account for the rapidity of the response. METHODS:
      To explore this phenomenon, the effects of two mechanistically distinct
      vasodilators, sodium nitroprusside (SNP) and hydralazine (HYD), on velocity
      increase, ex vivo platelet aggregation and thrombosis, were assessed in the rat
      ferric chloride-induced thrombosis model. RESULTS: Sodium nitroprusside (10, 30
      and 50 microg/kg/min i.v.) and hydralazine (0.1, 0.3 and 1.0 mg/kg/min i.v.)
      reduced the mean arterial pressure with the higher dose regimens eliciting
      equivalent hypotensive effects. Both sodium nitroprusside and hydralazine blunted
      the initial velocity increase, but only sodium nitroprusside significantly
      reduced the incidence of thrombotic occlusion. No differences in ex vivo platelet
      aggregation responses to adenosine diphosphate (ADP), collagen (COLL) and
      arachidonic acid (AA) were observed between the sodium nitroprusside and
      hydralazine treatment groups. However, platelet aggregation response to thrombin
      was significantly reduced in the 50 microg/kg/min i.v. sodium nitroprusside
      compared to the 1.0 mg/kg/min i.v. hydralazine and vehicle groups. CONCLUSIONS:
      Inhibition of the initial velocity increase by two mechanistically distinct
      vasodilators, and the dissociation between this velocity change and
      antithrombotic efficacy, support the hypothesis that the early velocity increase
      results from a change in vascular tone rather than due to enhanced platelet
      activation and thrombus formation. Inhibition of thrombin-induced platelet
      activation may contribute to the antithrombotic actions of sodium nitroprusside
      in this preparation.

PMID- 14644082
TI  - The relative importance of the ADP receptors, P2Y12 and P2Y1, in thrombin-induced
      platelet activation.
AB  - The objective of this study was to test the relative importance of the two
      adenosine diphosphate (ADP) receptors P2Y(1) and P2Y(12) in thrombin-induced
      platelet activation using specific receptor antagonists. Blood from healthy
      volunteers was incubated with MRS2179, a reversible P2Y(1) antagonist, or AR
      C69931, a reversible P2Y(12) antagonist prior to activation with different
      concentrations of ADP or thrombin. Platelet function in whole blood was assayed
      by flow cytometry using the antibody PAC-1 to estimate the expression of
      conformational active alpha(IIb)beta(3), the fibrinogen receptor. Complete
      inhibition of P2Y(12) or P2Y(1) abolished the ADP response, but only inhibition
      of P2Y(12) reduced the thrombin-induced response. The relative inhibition of the
      thrombin response by complete inhibition of P2Y(12) was most pronounced at
      thrombin concentrations just enough for complete PAR1 cleavage, which is
      sufficient to release all ADP, giving 70-86% inhibition. Above this
      concentration, the relative importance of P2Y(12) inhibition decreased due to
      activation of ADP independent pathways. This study supports P2Y(12) as a drug
      target compared with P2Y(1).

PMID- 14644083
TI  - Identification of low-density platelet populations with increased reactivity and
      elevated alpha-granule content.
AB  - The present study examines biochemical and functional characteristics of platelet
      density subpopulations together with their ability to mobilise intracellular
      fibrinogen when activated. Platelets from three healthy volunteers were
      investigated. The total platelet population was separated according to density in
      a linear Percoll gradient in a plasma-free milieu containing EDTA that binds
      soluble Ca(2+). Subsequently, platelets from each individual were divided
      according to density into 11 or 12 aliquots. In all fractions, we determined
      platelet count, intracellular P-selectin and the ADP-evoked platelet fibrinogen
      binding as a measure of platelet reactivity together with the platelet dense body
      content. The work demonstrates that platelets use stored intracellular fibrinogen
      when activated. It also shows that the platelet-fibrinogen binding can be
      initiated in a surrounding depleted of Ca(2+) and fibrinogen. Moreover, the study
      demonstrates subpopulations of light platelets having increased reactivity and
      more alpha-granules but less dense bodies. The biological significance of the
      findings needs to be elucidated.

PMID- 14644084
TI  - Increase in hepatic mRNA expression of coagulant factors in type 2 diabetic model
      mice.
AB  - AIM: The purpose of the study is to investigate whether hypercoagulation in
      diabetes is observed not only in increased plasma levels of the coagulative
      factors but also in increased hepatic mRNA levels. MATERIALS AND METHODS: The age
      related changes of coagulation factors were determined using KK and KK-A(y) mice
      as a model for human type 2 diabetes mellitus. Expression of the alpha-, beta-
      and gamma-chains of fibrinogen-mRNA and prothrombin-mRNA from the mouse liver was
      examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      Hemoglobin A(1c) (HbA(1C)), plasma fibrinogen, triglyceride and insulin levels
      increased apparently, especially in KK-A(y) mouse at 4 months old. The mRNA
      levels of gamma-chain of fibrinogen significantly increased at 3 and 4 months of
      age in both mice. The mRNA levels of alpha- and beta-chains of fibrinogen and
      prothrombin were significantly increased in 4-month-old KK-A(y) mouse.
      CONCLUSIONS: These results suggest that the increase in hepatic mRNA expression
      of coagulant factors contributes to the hypercoagulable state in type 2 diabetic
      mice.

PMID- 14644085
TI  - Effects of lepirudin, argatroban and melagatran and additional influence of
      phenprocoumon on ecarin clotting time.
AB  - INTRODUCTION: Direct thrombin inhibitors (DTI) prolong the ecarin clotting time
      (ECT). Oral anticoagulants (OA) decrease prothrombin levels and thus interact
      with actions of DTIs on the ECT method during concomitant therapy. MATERIALS AND
      METHODS: Actions of lepirudin, argatroban and melagatran on ECT were investigated
      in normal plasma (NP) and in plasma of patients (n=23 each) on stable therapy
      with phenprocoumon (OACP). Individual line characteristics were tested
      statistically. RESULTS: Control ECT in OACP was prolonged compared to NP (50.1+/
      0.9 vs. 45.7+/-0.8 s; p<0.001). Lepirudin prolonged the ECT linearly. Argatroban
      and melagatran delivered biphasic dose-response curves. OA showed additive
      effects on the ECT of lepirudin but not of argatroban and melagatran. Both in NP
      and OACP, the first and second slopes of melagatran were steeper compared to
      argatroban (primary analysis; p<0.001). When using the same drug, slopes in OACP
      were steeper than in NP (secondary analysis; p<0.001). At similar molar
      concentrations, the crossing points of both slopes were significantly higher with
      melagatran (323.1+/-11.0 s in NP and 333.2+/-8.2 s in OACP) than with argatroban
      (219.6+/-14.7 and 248.4+/-15.2 s) corresponding to ratios of 7.1+/-0.2 and 6.7+/
      0.2 (melagatran) vs. 4.8+/-0.3 and 4.9+/-03 with argatroban (p<0.0001).
      DISCUSSION: The patterns of interactions between vitamin K antagonists and DTI
      effects are different for bivalent (increase of slope without affecting
      linearity) and monovalent inhibitors (slight increase or alteration of nonlinear
      slopes), but there are also differences between the two monovalent inhibitors on
      thrombin inhibition as determined by ECT.

PMID- 14644086
TI  - Fibrinogenolytic and procoagulant activities in the hemorrhagic syndrome caused
      by Lonomia obliqua caterpillars.
AB  - The hemorrhagic syndrome caused by accidents with caterpillars of the genus
      Lonomia has been the focus of several clinical and biochemical studies, since its
      venom is composed of many active principles that interfere with the hemostatic
      system. Whereas a fibrinolytic agent has been characterized in the venom of
      Lonomia achelous, in Lonomia obliqua, only a prothrombin activator activity has
      been reported so far, even though both species cause similar bleeding disorders,
      characterized by hemorrhage, disseminated intravascular coagulation (DIC), and
      acute renal failure. Considering the possibility that the hemorrhagic syndrome
      resulting from envenoming by L. obliqua may be due to fibrinolytic and
      procoagulant activities acting together, we decided to investigate the effects of
      bristle extract (BE) of this species upon blood coagulation and
      fibrin(ogen)olysis. This study shows that besides a procoagulant activity related
      to the activation of prothrombin, the venom contains at least one
      fibrin(ogen)olytic activity, as shown by fibrinolysis in a fibrin (F) plate
      assay, by interference in thrombin-catalyzed fibrinocoagulation, and by
      polyacrylamide gel electrophoresis profile of fibrin and fibrinogen (Fg)
      degradation. Considering that a recombinant prothrombin activator from L. obliqua
      has been suggested in other studies to be used as an anti-thrombotic agent, it is
      important in the first place to better characterize the different active
      principles of this venom.

PMID- 14644087
TI  - Quantitative evaluation of thrombosis by electrochemical methodology.
AB  - Electrochemical reactions between blood and metal electrodes have been studied
      since 1928. Little is known about the actual current density induced during the
      reaction. In this study, an in situ continuous monitoring method was developed to
      detect the progress of thrombosis on an oxidized 316L stainless steel coil was
      deployed inside the artery. Three stages of current density were observed on a
      316L wire passivated with polycrystalline oxide film. In contrast, no significant
      current density was detected for a wire passivated with amorphous oxide film.
      Results showed that this in situ electrochemical monitoring method is sensitive
      to the passivated film on the stainless steel coil and could provide efficient
      and reliable information on the control of thrombosis on cardiovascular devices.

PMID- 14644088
TI  - Pharmacokinetics of pulse-sprayed recombinant tissue plasminogen activator for
      deep venous thrombosis.

PMID- 14644089
TI  - Screening for multiple hereditary hypercoagulability factors using the
      amplification refractory mutation system.
AB  - Many hereditary factors have been implicated in the development of arterial
      and/or venous thromboembolic diseases. A number of these risk factors can be
      identified by the amplification refractory mutation system (ARMS). However, the
      underlying technical conditions for performing ARMS are highly variable, and
      depend on which risk factors are being analyzed. We have now developed a novel
      ARMS-based system to simultaneously screen for multiple hypercoagulability
      factors under identical PCR conditions. This can greatly simplify the process of
      screening for hereditary hypercoagulability.

PMID- 14644090
TI  - Retroperitoneal hematoma following tirofiban and enoxaparin coadministration in a
      patient with acute coronary syndrome.

PMID- 14644091
TI  - IMGT-ONTOLOGY and IMGT databases, tools and Web resources for immunogenetics and
      immunoinformatics.
AB  - The international ImMunoGeneTics information system (IMGT; http://imgt.cines.fr),
      is a high quality integrated information system specialized in immunoglobulins
      (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related
      proteins of the immune system (RPI) of human and other vertebrates, created in
      1989, by the Laboratoire d'ImmunoGenetique Moleculaire (LIGM; Universite
      Montpellier II and CNRS) at Montpellier, France. IMGT provides a common access to
      standardized data which include nucleotide and protein sequences, oligonucleotide
      primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures.
      IMGT consists of several sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB,
      IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB) and one 3D structure database
      (IMGT/3Dstructure-DB), interactive tools for sequence analysis (IMGT/V-QUEST,
      IMGT/JunctionAnalysis, IMGT/PhyloGene, IMGT/Allele-Align), for genome analysis
      (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView) and for 3D structure analysis
      (IMGT/StructuralQuery), and Web resources ("IMGT Marie-Paule page") comprising
      8000 HTML pages. IMGT other accesses include SRS, FTP, search by BLAST, etc. By
      its high quality and its easy data distribution, IMGT has important implications
      in medical research (repertoire in autoimmune diseases, AIDS, leukemias,
      lymphomas, myelomas), veterinary research, genome diversity and genome evolution
      studies of the adaptive immune responses, biotechnology related to antibody
      engineering (single chain Fragment variable (scFv), phage displays, combinatorial
      libraries) and therapeutical approaches (grafts, immunotherapy). IMGT is freely
      available at http://imgt.cines.fr.

PMID- 14644092
TI  - Enhancement of death-receptor induced caspase-8-activation in the death-inducing
      signalling complex by uncoupling of oxidative phosphorylation.
AB  - Signalling through the death receptor CD95 induces apoptosis by formation of a
      signalling complex at the cell membrane and subsequent caspase-8 and caspase-3
      activation. Treatment of Jurkat T cells with protonophores across the
      mitochondrial membrane such as 2,4-dinitrophenol (DNP) enhances the death
      inducing capacity of CD95. In this study, we show that this enhancement is due to
      the specific acceleration of caspase-8-processing and activation at the CD95
      receptor. DNP-treatment did not affect NF-kappaB-induction by CD95.
      Immunoprecipitation experiments showed that the amounts of the adapter FADD/MORT1
      and pro-caspase-8 at the CD95-receptor were not altered by DNP. Subcellular
      fractionation studies revealed that the amount of mature caspase-8 but not pro
      caspase at the membrane was increased following CD95-stimulation in the presence
      of DNP. As a consequence of caspase-activation, c-FLIP-levels in the cytosol
      decreased. In Jurkat cells overexpressing c-FLIPS, DNP was still able to enhance
      caspase-activation. The enhancing capacity of DNP was seen in some cell lines
      (Jurkat, CEM and HeLa) but not in SKW6 cells and was also found in mitogen
      stimulated human T cells. Furthermore, the enhancement extended to TRAIL-induced
      caspase-activation. Thus, a mechanism exists by which caspase-8-activation can be
      accelerated at death receptors and this mechanism can be triggered by targeting
      mitochondrial oxidative phosphorylation.

PMID- 14644093
TI  - Activation of innate immune responses by IL-2-expressing Salmonella typhimurium
      is independent of Toll-like receptor 4.
AB  - We previously demonstrated that an attenuated strain of Salmonella enterica
      serovar Typhimurium, engineered to express IL-2 (strain GIDIL2), is cleared more
      rapidly than its parental, non-cytokine-expressing, strain (designated BRD509)
      from the reticuloendothelial system of susceptible BALB/c mice. This early
      clearance correlated with the induction of a strong innate immune response within
      a few hours of administration of GIDIL2 organisms. In the present study, we
      wished to assess the contribution of LPS recognition to GIDIL2-induced immune
      responses using Toll-like receptor 4 (TLR4) mutant C3H/HeJ mice. In contrast to
      LPS responder mice, both BRD509 and GIDIL2 strains persisted at higher levels in
      LPS non-responder animals. However, the GIDIL2 bacterial loads in the peritoneal
      cavity and spleen, recovered over a period of 21 days post infection, were
      consistently lower than the corresponding CFUs of the BRD509 strain. Direct
      evidence for the induction of innate immunity was shown by demonstrating
      increased NK cell cytotoxicity, NOS2 gene expression, and nitric oxide synthesis
      by peritoneal cells obtained as early as 2h after infection with GIDIL2, but not
      BRD509, organisms. Unlike BALB/c mice, however, these responses failed to afford
      any protection against virulent challenge in C3H/HeJ mice. Taken together, our
      data demonstrate that despite the induction of innate immune responses by IL2
      expressing organisms, this was not sufficient to induce protection in TLR4 mutant
      mice.

PMID- 14644094
TI  - Signaling and protein associations of a cell permeable CD40 complex in B cells.
AB  - Signaling through the CD40 receptor activates diverse molecular pathways in a
      variety of immune cell types. To study CD40 signaling complexes in B cells, we
      produced soluble CD40 cytoplasmic domain multimers that translocate across cell
      membranes and engage intracellular CD40 signaling pathways. As visualized by
      fluorescence microscopy, rapid transduction of recombinant Antennapedia
      isoleucine zipper (Izip)-CD40 cytoplasmic domain fusion protein (Antp-CD40)
      occurred in both the DND39 B cell line and human tonsillar B cells. Upon cellular
      entry, Antp-CD40 activated NF-kappaB-dependent transcription, induced proteolytic
      processing of p100 to the p52/NF-kappaB2 subunit, and increased expression of
      CD80 and CD54 on the surface of B cells. Antp-CD40 transduction of B cells did
      not, however, activate detectable levels of p38 mitogen-activated protein kinase
      or c-Jun N-terminal kinase and did not up-regulate CD95 expression. Analysis of
      Antp-CD40 complexes recovered from transduced B cells revealed that Antp-CD40
      associated with endogenous TRAF3 and Ku proteins. Multimerization of Antp-CD40,
      or extensive clustering of transmembrane CD40, diminished the disruptive effect
      of the T254A mutation in the TRAF2/3 binding site of the CD40 cytoplasmic domain.
      Taken together, these results indicate that Antp-CD40 mimics some of the natural
      CD40 signaling pathways in B cells by assembling partially functional signaling
      intermediates that do not require plasma membrane localization. We present a
      novel approach for delivering pre-activated, soluble receptor cytoplasmic domains
      into cells and recovering intact signaling complexes for molecular analysis.

PMID- 14644095
TI  - Upstream stimulatory factor but not c-Myc enhances transcription of the human
      polymeric immunoglobulin receptor gene.
AB  - Secretory antibodies protect mucosal surfaces from ingested, inhaled and sexually
      transmitted pathogens. The polymeric immunoglobulin receptor (pIgR) transports
      antibodies across mucosal epithelia into external secretions. We and others have
      identified a region of the human polymeric immunoglobulin receptor gene (locus
      PIGR) that is sufficient for basal transcriptional activity. An E-Box motif,
      which binds transcription factors of the basic helix-loop-helix/leucine zipper
      (bHLH/zip) family, was identified as a major regulatory element in the PIGR gene
      promoter. Transient transfection of PIGR promoter reporter plasmids in intestinal
      epithelial cell (IEC) lines suggested that the transcription factors upstream
      stimulatory factor (USF) and c-Myc may exert opposing effects on PIGR promoter
      activity. Mutations within and flanking the E-Box that favored USF binding
      enhanced promoter activity, while mutations that favored c-Myc binding reduced
      promoter activity. Ectopic expression of USF1 or USF2 enhanced PIGR promoter
      activity, while exogenous c-Myc did not. Electrophoretic mobility shift assays
      (EMSA) demonstrated that USF1 and USF2 bound to the E-Box motif as homo- and
      heterodimers. Chromatin immunoprecipitation (ChIP) demonstrated that USF proteins
      bind the PIGR promoter in vivo, which is enriched in acetylated histones. E-Box
      motifs are commonly observed in promoters of genes that are highly expressed in
      the human colon. Genes that are down-regulated in colorectal cancer, including
      PIGR, frequently have non-canonical E-Boxes, while genes that are up-regulated in
      colorectal cancer generally have canonical E-Boxes. The results of our
      experiments may shed light on the mechanisms of dysregulated expression of pIgR
      in inflammatory bowel disease and colorectal cancer, diseases associated with
      aberrant expression of c-Myc.

PMID- 14644096
TI  - Microglial activation and increased synthesis of complement component C1q
      precedes blood-brain barrier dysfunction in rats.
AB  - A reliable way to visualise the state of microglial activation is to monitor the
      microglial gene expression profile. Microglia are the only CNS resident cells
      that synthesise C1q, the recognition sub-component of the classical complement
      pathway, in vivo. C1q biosynthesis in resting ramified microglia is often low,
      but it increases dramatically in activated microglia. In this study, the
      expression of C1q was used to monitor microglial activation at all stages of 3
      chloropropanediol-induced neurotoxicity, a new model of blood-brain barrier (BBB)
      breakdown. In rats, 3-chloropropanediol produces very focused lesions in the
      brain, characterised by early astrocyte swelling and loss, followed by neuronal
      death and barrier dysfunction. Using in situ hybridisation, immunohistochemistry,
      and real-time RT-PCR, we found that increased C1q biosynthesis and microglial
      activation precede BBB dysfunction by at least 18 and peak 48 h after injection
      of 3-chloropropanediol, which coincides with the onset of active haemorrhage.
      Microglial activation is biphasic; an early phase of global activation is
      followed by a later phase in which microglial activation becomes increasingly
      focused in the lesions. During the early phase, expression of the pro
      inflammatory mediators interleukin-1beta (IL1beta), tumour necrosis factor alpha
      (TNFalpha) and early growth response-1 (Egr-1) increased in parallel with C1q,
      but was restricted to the lesions. Expression of C1q (but not IL1beta, TNFalpha
      or Egr-1) remains high after BBB function is restored, and is accompanied by late
      up-regulation of the C1q-associated serine proteases, C1r and C1s, suggesting
      that microglial biosynthesis of the activation complex of the classical pathway
      may support the removal of cell debris by activation of complement.

PMID- 14644097
TI  - Optimization of codon pair use within the (GGGGS)3 linker sequence results in
      enhanced protein expression.
AB  - Here, we report that a significant increase in recombinant fusion antibody
      expression can be accomplished by adjusting the nucleotide sequence to conform to
      certain codon pairing rules. We investigated the expression of a protein in which
      a single chain Fv specific for HER2/neu with VH and VL joined by a flexible
      (GGGGS)3 linker was linked to the CH3 of a human anti-rat transferrin receptor
      IgG3 heavy chain with the same flexible (GGGGS)3 linker. In initial experiments
      we failed to achieve significant expression of this protein. However, when we
      made a single nucleotide change in each (GGGGS)3 linker we were able to achieve
      expression The change of one nucleotide within each linker did not alter either
      the amino acid sequence or the frequency score of these codon triplets' usage in
      mammalian cells. Instead they removed two codon pairs predicted to be detrimental
      to expression. In a transient transfection assay we find that this change results
      in an over 30-fold increase in expression that is not the result of an increase
      in the level of accumulated mRNA. In addition, the changes made it possible to
      isolate stably transfected mammalian cell clones producing high levels of fusion
      protein, which had not been possible using the original gene.

PMID- 14644099
TI  - Retrotranslocation of MHC class I heavy chain from the endoplasmic reticulum to
      the cytosol is dependent on ATP supply to the ER lumen.
AB  - MHC class I heavy chains (HC) that fail to acquire a mature conformation in the
      endoplasmic reticulum (ER) as a result of defective folding or assembly with
      beta2-microglobulin, or lack of appropriate peptide cargo are retrotranslocated
      through the Sec61 channel to the cytosol for degradation by proteasomes. The
      mechanisms involved in ER retrotranslocation of HC are as yet incompletely
      understood. Using a microsomal system, we characterized the molecular
      requirements for the release of HC into the soluble fraction. Extraction of
      ubiquitinated HC was facilitated by cytosol, or by addition of proteins that
      stabilized the membrane association of the cytoplasmic ATPase p97. Functional
      proteasomes were not needed for HC mobilization. ATP supply to the ER lumen was
      found to be an essential factor since an inhibitor of the ATP importing pump in
      the ER membrane blocked HC release. Also non-hydrolyzable ATP analogs delivered
      to the ER lumen facilitated HC export suggesting that ATP binding by ER
      chaperones rather than ATP hydrolysis is involved.

PMID- 14644098
TI  - PU.1 as a chromatin accessibility factor for immunoglobulin genes.
AB  - The hematopoietic-specific transcription factor PU.1 is a chromatin accessibility
      factor, based on analysis of the immunoglobulin heavy chain intronic (mu)
      enhancer. Whether PU.1 functions as an accessibility factor for additional PU.1
      regulated genes is unknown. Outside the constraints of chromatin, PU.1 binds and
      activates transcription through both mu and kappa3' immunoglobulin enhancers,
      among others. The DNA-binding ETS domain of PU.1 is sufficient for activating
      both enhancers in an extrachromosomal context. New data show that the ETS domain
      of PU.1 is sufficient for increasing accessibility of a closed mu enhancer
      chromatin structure proximal to the PU.1-binding site. In contrast, PU.1 does not
      alter widespread chromatin accessibility. Furthermore, PU.1 does not induce
      accessibility proximal or distal to its binding site on the kappa3' enhancer.
      Taken together the data demonstrate that PU.1 induces chromatin accessibility
      proximal to its binding site at a locus activated early in development, the mu
      locus. PU.1 does not function as an accessibility factor for the kappa3'
      enhancer, which regulates a locus important for later stages of B cell
      development. We conclude that PU.1 is a context-dependent chromatin accessibility
      factor that, alone, cannot establish widespread accessibility required for
      critical developmental processes such as antigen receptor recombination.

PMID- 14644100
TI  - Deficits in facial emotion perception in adults with recent traumatic brain
      injury.
AB  - We examined whether facial emotion perception was compromised in adults with
      recent traumatic brain injury (TBI). Few studies have examined emotion perception
      in TBI; those that have, examined chronic patients only. Recent and chronic TBI
      populations differ according to degree of functional reorganization of the brain,
      use of compensatory strategies, and severity of cognitive impairments--any of
      which might differentially affect presentation of emotion perception deficits. A
      secondary aim of the study was to utilize the TBI population--in whom diffuse
      axonal injury (DAI) is a cardinal neurological feature--to examine the suggestion
      of Adolphs et al. [Journal of Neuroscience 20(7) (2000) 2683] that damage to
      white matter tracts should give rise to emotion perception deficits. METHODS:
      Thirty TBI participants and 30 age-matched controls were tested. A 2 x 3 mixed
      design was employed. The dependent variable was accuracy on neutral and emotional
      face perception tests. RESULTS: (1) The TBI group performed significantly less
      accurately than the matched controls on the facial emotion perception tasks,
      whereas the groups performed equivalently on a non-emotional face perception
      control task. (2) A sub-group of TBI participants without evidence of focal
      injury to areas of the brain most commonly implicated in facial emotion
      perception was as impaired on the emotion perception tasks as a second sub-group
      who had sustained focal lesions to these areas. This suggests an alternative
      neurological mechanism for deficits in the first sub-group, such as DAI.
      CONCLUSIONS: Patients with recently acquired TBI are impaired in their ability to
      perceive emotions in faces. DAI alone may cause facial emotion perception
      deficits.

PMID- 14644101
TI  - Temporal processing in poor adult readers.
AB  - The aim of this study was to investigate the relationships between two different
      temporal processing tasks and word identification performance in skilled,
      dyslexic and poor adult readers. In Experiment 1 spatial and temporal sequencing
      tasks were conducted. It was found that adult dyslexics were significantly less
      accurate than skilled readers across all conditions in the temporal sequencing
      task, and when higher numbers of stimuli were presented in the spatial task.
      Experiment 2 replicated Experiment 1 in the temporal sequencing task and also
      found that poor readers had significantly higher motion coherence thresholds than
      those found in the skilled reader group. Ten percent of the variance in coherence
      thresholds was accounted for by performance on the temporal sequencing task.
      Multiple regression analyses determined that performance on the two temporal
      tasks could explain seventy percent of the variance in word identification
      scores, with the temporal sequencing task making the larger independent
      contribution. Experiment 3 replicated the findings of Experiment 2, while taking
      into account IQ, verbal memory and processing speed. Three things were concluded.
      First, the temporal tasks measure different aspects of temporal processing. The
      contribution to performance of higher-level perceptual and attentional components
      of the temporal sequencing task accounts for the relatively weak correlation
      found between the two measures. While sensory sensitivity to motion is measured
      at MT, the involvement of this area and PPC in higher-level perceptual and
      attentional processes is suggested by the findings of this study. Second, the
      association between temporal sequencing and reading skills may provide a stronger
      link between neural processing and poor reading skills than basic sensory
      processing measures alone, suggesting that a sensory magnocellular (M) system
      deficit cannot fully explain the relationship found between reading and visual
      neural processing. Third, problems with rapid sequential processing are predicted
      to be a generalised problem in poor adult readers, whether they are formally
      classified as dyslexic, or are poor performers on measures of word
      identification. Temporal processing may follow a distribution similar to that
      found for word identification skills.

PMID- 14644102
TI  - Facial closure: interrelationship with facial discrimination, other closure
      tests, and subjective contour illusions.
AB  - Findings from previous research have argued for the dissociation of two visual
      perceptual tasks traditionally thought to be mediated by the nondominant
      hemisphere (i.e. perceptual closure and facial discrimination). This, primarily
      methodological, study examined the extent to which the facial closure measure
      (Mooney closure faces test) involves "closure" and/or facial discrimination. A
      factor analysis of six visual perceptual measures, carried out separately for
      left brain damaged (LBDs, n=33) and right brain damaged (RBDs, n=30) patients,
      resulted in two relatively independent factors (i.e. a closure factor and a
      facial discrimination factor), with the Mooney closure faces test loading on
      both. The mixed factorial structure did not aid the facial closure measure's
      sensitivity to right-sided brain disease. Moreover, age and education
      intercorrelated differently with the two factors. Results argue for the use of
      more discrete visual-perceptual measures when examining perceptual functioning
      and/or right hemisphere integrity, and imply the existence of at least two
      discrete cortical level visual-perceptual neural systems.

PMID- 14644103
TI  - Effective binocular integration at the midline requires the corpus callosum.
AB  - To study the role of the corpus callosum (CC) in midline binocular integration,
      the effects of late callosotomy and congenital CC agenesis on the ability to
      perceive dichoptic plaid motion was assessed. Coherent motion was well perceived
      at all locations in the visual field under dioptic viewing but not along the
      vertical meridian (VM) when the components were dichoptically presented. This
      deficit was totally abolished in the agenesis subject and reduced in the
      callosotomized individual when stimulus size was increased beyond the VM.
      Electrophysiological correlates were also examined by recording visual evoked
      potentials and these showed that the P1/N2 components were abnormal for small
      dichoptic stimuli presented on the midline. These findings attest to the
      importance of the contribution of CC to midline binocular integration and the
      effects of cerebral plasticity.

PMID- 14644104
TI  - The effect of ipsilesional cues on line-bisection errors: the importance of
      predictive value.
AB  - Patients with unilateral neglect were tested on a line-bisection task in which
      vertical lines were added to the ipsilesional or contralesional end. During some
      blocks, these vertical lines accurately predicted the horizontal length of the
      line, while on other blocks the vertical lines had little predictive value. We
      found that much of the improvement for ipsilesional vertical bars can be
      explained by their ability to predict the extent of the horizontal line. These
      results suggest that the predictive value of a ipsilesional cue is responsible
      for the reduction in line-bisection errors noted by Halligan and Marshall
      [Neuropsychologia 32 (1994) 13]. This effect of the predictive ipsilesional cue
      may work in combination with the expanded attentional effects posited by the
      ipsilesional contraction model that they proposed.

PMID- 14644105
TI  - Auditory lexical decision, categorical perception, and FM direction
      discrimination differentially engage left and right auditory cortex.
AB  - Recent neuroimaging and neuropsychological data suggest that speech perception is
      supported in bilaterally auditory areas. We evaluate this issue building on well
      known behavioral effects. While undergoing positron emission tomography (PET),
      subjects performed standard auditory tasks: direction discrimination of frequency
      modulated (FM) tones, categorical perception (CP) of consonant-vowel (CV)
      syllables, and word/non-word judgments (lexical decision, LD). Compared to rest,
      the three conditions led to bilateral activation of the auditory cortices.
      However, lateralization patterns differed as a function of stimulus type: the LD
      task generated stronger responses in the left, the FM task a stronger response in
      the right hemisphere. Contrasts between either words or syllables versus FM were
      associated with significantly greater activity bilaterally in superior temporal
      gyrus (STG) ventro-lateral to Heschl's gyrus. These activations extended into the
      superior temporal sulcus (STS) and the middle temporal gyrus (MTG) and were
      greater in the left. The same areas were more active in the LD than the CP task.
      In contrast, the FM task was associated with significantly greater activity in
      the right lateral-posterior STG and lateral MTG. The findings argue for a view in
      which speech perception is mediated bilaterally in the auditory cortices and that
      the well-documented lateralization is likely associated with processes subsequent
      to the auditory analysis of speech.

PMID- 14644106
TI  - Lexical production in children with Williams syndrome: spontaneous use of gesture
      in a naming task.
AB  - This study investigates lexical organization and lexical retrieval in children
      with Williams syndrome (WS), by examining both naming accuracy and accompanying
      use of gestures in a picture-naming task. Ten children with the genetic disorder
      of Williams syndrome (age range: 9.5-12.9) were compared with 20 typically
      developing children, 10 matched for chronological age (CA) and 10 for mental-age
      (MA). Lexical production was measured by administering the Boston Naming test
      (BNT). Older typically developing children performed significantly better than
      the other two groups. No differences in accuracy were found between the children
      with WS and the typically developing children matched for mental-age. The overall
      distribution of error types displayed by children with WS indicate that the
      lexical-semantic organization is similar to that of typically developing
      children. However, compared to controls, the WS group produced more iconic
      gestures during the task, in patterns that suggest the existence of specific word
      finding difficulties in these children. Results are discussed within the
      framework of recent theories on the role of gesture in speech production.

PMID- 14644107
TI  - Understanding 'not': neuropsychological dissociations between hand and head
      markers of negation in BSL.
AB  - Simple negation in natural languages represents a complex interrelationship of
      syntax, prosody, semantics and pragmatics, and may be realised in various ways:
      lexically, morphologically and prosodically. In almost all spoken languages, the
      first two of these are the primary realisations of syntactic negation. In
      contrast, in many signed languages negation can occur without lexical or
      morphological marking. Thus, in British Sign Language (BSL), negation is
      obligatorily expressed using face-head actions alone (facial negation) with the
      option of articulating a manual form alongside the required face-head actions
      (lexical negation). What are the processes underlying facial negation? Here, we
      explore this question neuropsychologically. If facial negation reflects lexico
      syntactic processing in BSL, it may be relatively spared in people with
      unilateral right hemisphere (RH) lesions, as has been suggested for other
      'grammatical facial actions' [Language and Speech 42 (1999) 307; Emmorey, K.
      (2002). Language, cognition and the brain: Insights from sign language research.
      Mahwah, NJ: Erlbaum (Lawrence)]. Three BSL users with RH lesions were
      specifically impaired in perceiving facial compared with manual (lexical and
      morphological) negation. This dissociation was absent in three users of BSL with
      left hemisphere lesions and different degrees of language disorder, who also
      showed relative sparing of negation comprehension. We conclude that, in contrast
      to some analyses [Applied Psycholinguistics 18 (1997) 411; Emmorey, K. (2002).
      Language, cognition and the brain: Insights from sign language research. Mahwah,
      NJ: Erlbaum (Lawrence); Archives of Neurology 36 (1979) 837], non-manual negation
      in sign may not be a direct surface realisation of syntax [Language and Speech 42
      (1999) 143; Language and Speech 42 (1999) 127]. Difficulties with facial negation
      in the RH-lesion group were associated with specific impairments in processing
      facial images, including facial expressions. However, they did not reflect
      generalised 'face-blindness', since the reading of (English) speech patterns from
      faces was spared in this group. We propose that some aspects of the linguistic
      analysis of sign language are achieved by prosodic analysis systems (analysis of
      face and head gestures), which are lateralised to the minor hemisphere.

PMID- 14644108
TI  - Belief and awareness: reflections on a case of persistent anosognosia.
AB  - Persisting anosognosia after acute lesions is relatively rare, and no case
      studies to date have reported functional scanning investigation of this disorder.
      This is a case report of an 85-year-old right-handed Scottish woman, EN, who
      showed persistent anosognosia for hemiplegia following a haemorrhagic stroke.
      Extensive damage in the right hemisphere caused left upper and lower limb flaccid
      hemiplegia and severe left-sided neglect. Lack of awareness for her deficits was
      still present 2 years after the stroke, when neurological, neuropsychological,
      and SPECT examinations were performed. Testing revealed severe left unilateral
      neglect and poor performance on verbal fluency tasks. EN had age normal memory
      performance, and her object recognition and praxic abilities were preserved. She
      showed no global reasoning or language problems apart from her abnormal beliefs.
      EN believed that she was able to walk and carry out several activities, in a
      context of other disorders of belief. SPECT scan showed marked hypoperfusion in
      the right parietotemporal cortex and this extended to the associative cortex in
      the right frontal regions. The persistence of anosognosia in this patient cannot
      be explained by memory impairments or global cognitive decline. A possible
      account might be that alteration in awareness was maintained by contingent right
      frontal and/or parietal dysfunction causing a suspension or change in the ability
      to monitor and check the 'real' and especially to assess the veracity of mental
      contents.

PMID- 14644109
TI  - Deficits in decoding emotional facial expressions in Parkinson's disease.
AB  - INTRODUCTION: The basal ganglia have numerous connections not only with the motor
      cortex but also with the prefrontal and limbic cortical areas. Therefore, basal
      ganglia lesions can disturb motor function but also cognitive function and
      emotion processing. The aim of the present study was to assess the consequences
      of Parkinson's disease (PD) on ability to decode emotional facial expressions
      (EFEs)-a method commonly used to investigate non-verbal emotion processing.
      METHODS: Eighteen PD patients participated in the study, together with 18 healthy
      subjects strictly matched with respect to age, education and sex. The patients
      were early in the course of the disease and had not yet received any
      antiparkinsonian treatment. Decoding of EFEs was assessed using a standardized,
      quantitative task where the expressions were of moderate intensity, i.e. quite
      similar to those experienced in everyday life. A set of tests also assessed
      executive function. Visuospatial perception, depression and anxiety were
      measured. RESULTS: Early in the course of the disease, untreated PD patients were
      significantly impaired in decoding EFEs, as well as in executive function. The
      deficits were significantly interrelated, although neither was significantly
      related to severity of the motor symptoms. Visuospatial perception was not
      impaired, and the patients' impairment was related neither to their depression
      nor to their anxiety score. The PD patients' impairment in decoding EFEs was
      related to a systematic response bias. CONCLUSION: Early in the course of PD, non
      verbal emotional information processing is disturbed. This suggests that in PD,
      nigrostriatal dopaminergic depletion leads not only to motor and cognitive
      disturbances but also to emotional information processing deficits. The observed
      correlation pattern does not enable adoption of a clear-cut position in the
      debate over totally or partially segregated functional organization of the basal
      ganglia circuits.

PMID- 14644110
TI  - Image of a line is not shrunk but neglected. Absence of crossover in unilateral
      spatial neglect.
AB  - Patients with left unilateral spatial neglect following right hemisphere lesions
      usually err rightward when bisecting a horizontal line. For very short lines
      (e.g. 25 mm), however, leftward errors or seemingly 'right' neglect is often
      observed. To explain this paradox of crossover in the direction of errors, rather
      complicated models have been introduced as to the distribution of attention.
      Neglect may be hypothesized to occur in representational process of a line or
      estimation of the midpoint on the formed image, or both. We devised a line image
      task using a computer display with a touch panel and approached the
      representational image of a line to be bisected. Three patients with typical left
      neglect were presented with a line and forced to see its whole extent with cueing
      to the left endpoint. After disappearance of the line, they pointed to the right
      endpoint, the left endpoint, or the subjective midpoint according to their
      representational image. The line image between the reproduced right and left
      endpoints was appropriately formed for the 200 mm lines. However, the images for
      the shorter 25 and 100 mm lines were longer than the physical lengths with
      overextension to the left side. These results proved the context effect that
      short lines may be perceived longer when they are presented in combination with
      longer lines. One of our patients had an extensive lesion that involved the
      frontal, temporal, and parietal lobes, and the other two had a lesion restricted
      to the posterior right hemisphere. The image for a fully perceived line may be
      represented far enough into left space even when left neglect occurs after a
      lesion that involves the right parietal lobe. The patients with neglect placed
      the subjective midpoint rightward from the centre of the stimulus line for the
      100 and 200 mm lines and leftward for the 25 mm lines. This crossover of
      bisection errors disappeared when the displacement of the subjective midpoint was
      measured from the centre of the representational line image. Left neglect may
      occur consistently in estimation of the subjective midpoint on the
      representational image, which may be explained by a simple rightward bias of
      attentional distribution.

PMID- 14644111
TI  - Parallel interhemispheric processing in aging and alcoholism: relation to corpus
      callosum size.
AB  - We tested parallel processing of visual information using the redundant targets
      effect (RTE) in 12 alcoholics and 13 matched controls. The paradigm was a simple
      reaction time (RT) task with targets presented in the same (uncrossed), opposite
      (crossed), or both (redundant) visual-fields. In older alcoholics (>50 years) the
      RT gain invoked by redundant targets did not exceed probability measures,
      suggesting compromised interhemispheric processing of parallel information in
      this subgroup compared with controls or younger alcoholics. The difference
      between crossed and uncrossed reaction times (CUD), an index of interhemispheric
      transfer time (ITT), was greater in older than younger subjects. Moreover, the
      CUD was negatively correlated with the corpus callosum (CC) total area and body
      in controls, supporting the concept of a structure-function relationship of
      interhemispheric transfer. This relationship was not found in alcoholics,
      although the midsagittal area of the CC, genu, and body but not intracranial
      volume (ICV), was significantly smaller in alcoholics than controls. These
      results suggest that chronic alcohol abuse together with advancing age exert
      subtle disruption on parallel interhemispheric processing reliant on callosal
      connections.

PMID- 14644113
TI  - Handling and pathology reporting of radical prostatectomy specimens.
AB  - Proper examination of radical prostatectomy (RP) specimens by the pathologists is
      critical in accurately determining the prediction of patient outcome. The
      pathology report should include relevant clinical information as well as provide
      prognostically useful data derived from the evaluation of the RP specimen.

PMID- 14644114
TI  - Lower urinary tract symptoms and male sexual dysfunction: the multinational
      survey of the aging male (MSAM-7).
AB  - OBJECTIVES: Lower urinary tract symptoms (LUTS), which are often caused by benign
      prostatic hypertrophy (BPH), and sexual dysfunction are common in older men, with
      an overall prevalence of >50% in men aged > or =50 years. Men with LUTS have been
      reported to experience sexual dysfunction, including ejaculatory loss, painful
      ejaculation, and erectile dysfunction. This study was conducted to investigate
      the relationship between LUTS and sexual problems in aging men. METHODS: A large
      scale, multinational survey was conducted in the US and six European countries to
      systematically investigate the relationship between LUTS and sexual dysfunction
      in older men. Detailed questionnaires were mailed to a national representative
      sample of men aged 50 to 80 years in each country. Selection was made on the
      basis of age, occupation, geographic region, and population density. LUTS and
      sexual function were assessed by validated symptom scales, including the
      International Prostate Symptom Score, the Danish Prostatic Symptom Score, and the
      International Index of Erectile Function. Subjects also completed a health and
      demographics questionnaire. RESULTS: A total of 34,800 surveys were mailed out,
      14,254 were completed and returned, and 12,815 were deemed evaluable and included
      in the analysis. Results were consistent from one country to another. Although
      90% of the men had LUTS, only 19% had sought medical help for urinary problems
      and only 11% were medically treated. Sexual activity was reported by 83% of the
      sample, with 71% reporting at least one episode of sexual activity during the
      previous 4 weeks. Sexual disorders and their bothersomeness were strongly related
      to both age and severity of LUTS. The relationship between sexual problems and
      LUTS is independent of comorbidities such as diabetes, hypertension, cardiac
      disease, and hypercholesterolemia. CONCLUSIONS: Sexual activity is common in a
      majority of men over age 50 and is an important component of overall quality of
      life. The presence and severity of LUTS are independent risk factors for sexual
      dysfunction in older men. These results highlight the clinical importance of
      evaluating LUTS in patients with sexual dysfunction, and the need to consider
      sexual issues in the management of patients with benign prostatic hypertrophy.

PMID- 14644115
TI  - Prevention of prostate cancer with finasteride: US/European perspective.
AB  - PURPOSE: Prostate cancer is the most common male cancer, affecting one man in
      six. Prevention of this disease, even in a subset of patients would have a
      significant impact on public health. The results of the National Cancer Institute
      sponsored Prostate Cancer Prevention Trial demonstrate that finasteride causes a
      substantial risk reduction across all known risk groups. We herein amplify on the
      results of this trial to assist patients and physicians in reaching
      individualized decisions. MATERIALS AND METHODS: The results of the Prostate
      Cancer Prevention Trial were reviewed. RESULTS: The PCPT demonstrated a 24.8%
      reduction in prostate cancer risk with the administration of finasteride. High
      grade cancers were noted in 6.4% of finasteride patients compared to 5.1% of men
      receiving placebo. The increase in high-grade tumors was seen within one year of
      finasteride exposure and did not increase over time. This observation, combined
      with previous evidence demonstrating an alteration in cytologic and architectural
      features of prostate cancer with hormonal therapy suggests that the differences
      in high-grade disease may be an artifact and that application of Gleason grading
      to these tumors may not be appropriate. DISCUSSION: Men should be presented the
      benefits and risks of taking finasteride and be assisted in integrating their
      sexual and urinary symptoms into their decision-making process. Blanket
      statements for or against the use of this medication ignore patient preferences
      and differential risk-benefit profiles from finasteride.

PMID- 14644117
TI  - Osteoporosis during continuous androgen deprivation: influence of the modality
      and length of treatment.
AB  - OBJECTIVE: To analyze the prevalence of osteoporosis in patients with prostate
      cancer with and without androgen ablation. To know the influence of the modality
      and the length of androgen ablation on the prevalence of osteoporosis. To analyze
      the relative risk of hip fracture. MATERIAL AND METHODS: In a cross-sectional
      study, we assessed bone densitometry at the Ward's triangle of the femoral neck
      in 110 patients with non-metastatic prostate cancer and without biochemical
      relapse. A cohort of 53 patients under continuous androgen suppression during a
      median period of 41 months (12-191) formed the study group and 57 age-matched
      patients that had been submitted to a radical prostatectomy formed a control
      group. RESULTS: Both subsets of patients had similar mean age (70.4 vs. 69.2,
      p=0.07). Mean bone mass was 0.70 g/cm2 in patients under androgen suppression and
      0.76 g/cm2 in the control group, p=0.06. The rate of osteoporosis was 41.5%
      (22/53) and 28.1% (16/57) respectively, p=0.16 and the odds ratio was 1.82 (95%
      CI 0,82-4.03). The rate of osteoporosis was 41.4% (12/29) in patients under
      maximal androgen blockade and 41.7% (10/24) in patients under chemical
      castration, p=0.735. According to the length of the androgen suppression the rate
      of osteoporosis was 36.4% when it was between 12 and 36 months, 42.1% from 36 to
      60 months and 50% when it was longer than 60 months. While the overall relative
      risk of hip fracture in the control group was 2.0, it was 2.4 when the length of
      androgen suppression was between 12 and 36 months, 2.9 between 36 and 60 months
      and 3.9 when it was longer than 60 months. CONCLUSIONS: Androgen suppression
      increases the prevalence of osteoporosis in patients with prostate cancer. The
      modality of continues androgen suppression seems not to affect its prevalence.
      However the length of androgen suppression would be related to its development.
      The relative risk of hip fracture is also increasing during the androgen
      suppression.

PMID- 14644118
TI  - Detection of chromosomal aberrations in prostate cancer by fluorescence in situ
      hybridization (FISH).
AB  - PURPOSE: Fluorescence in situ hybridization (FISH) is a powerful tool for
      quantitative analysis of chromosomes and genes and can be applied in a variety of
      specimens, including cell cultures, isolated nuclei from fresh and fixed tissues,
      and histological tissue sections. For detection of numerical chromosome
      aberrations, we examined prostatic cancer samples at our department. In addition,
      we also observed primary and secondary aberrations taking part in the initiation
      and progression of tumours. MATERIALS AND METHODS: FISH using chromosome-specific
      alpha-satellite DNA probes for chromosomes 7, 8, 9, 10, 17, X and Y was performed
      on 19 prostatic cancer and 19 benign prostatic hyperplasia (BPH) samples obtained
      from transurethral resection (TUR) and archival paraffin-embedded blocks.
      RESULTS: Numerical aberrations were observed in 41% of the tumours studied. A
      range of aberrant copy numbers of chromosome 9 (68%), 7 (63%), 8 (58%), 17 (37%),
      Y (32%) and 10 (26%) was observed. We did not observe significant aberrations in
      BPH samples. In prostate cancer patients, chromosomes 7 (47%), 8 (58%) and 9
      (63%) were monosomic by FISH. Monosomy 8 and 9 were significant differences
      (p>0.05) between prostate cancer and BPH patients. CONCLUSIONS: FISH analysis
      could be observed an one of strongest methods of analysis in detecting numerical
      aberrations of individual chromosomes with application to paraffin-block samples,
      metaphase and, interphase nuclei. To our knowledge, this analysis is firstly
      studied in Turkish patients. Therefore, results of this analysis may be important
      for Turkish patients.

PMID- 14644116
TI  - Combined reporting of cancer control and functional results of radical
      prostatectomy.
AB  - INTRODUCTION: The results of radical prostatectomy (cancer control, continence
      and sexual potency) are currently presented separately, while the success of this
      surgery depends on a combination of good cancer control with maintenance of
      continence and erections. We propose a score to jointly evaluate and report
      cancer control and functional results. METHODS: The results of 205 radical
      prostatectomies were studied at one year. Cancer control was evaluated by PSA.
      Continence and sexual potency were evaluated by a self-administered
      questionnaire. Each patient was attributed 0 or 4 points according to the
      presence of absence of biochemical progression (PSA>0.2 ng/ml), 0 or 2 points
      according to the presence or absence of urinary incontinence (use of pads) and 0
      or 1 point according to the presence or absence of impotence (no erections). The
      sum of these points provided a score classifying the patient into 8 distinct
      categories, from 0 to 7, each corresponding to a specific status (from 0 (0+0+0):
      no cancer control-incontinence-impotence to 7 (4+2+1): cancer control-continence
      sexual potency). RESULTS: One year after the operation, 175 (85%) of patients had
      a PSA less than 0.2 ng/ml, 135 (65.8%) were continent and 64 (32.7%) reported
      erections. All patients with a score > or =4 had good cancer control, with no
      functional disorders for a score of 7 (4+2+1) (20%), no disorders of continence
      for a score of 6 (4+2+0) (31.5%), no disorders of erection for a score of 5
      (4+0+1) (8.3%), or with incontinence and impotence for a score of 4 (4+0+0)
      (21.9%). All patients with a score <4 had a PSA>0.2 ng/ml, but with no functional
      disorders for a score of 3 (0+2+1) (2.4%), no incontinence for a score of 2
      (0+2+0) (8.3%), and no impotence for a score of 1 (0+0+1) (1.9%). 1.9% of
      patients were incontinent, impotent and showed signs of biochemical progression
      (score 0=0+0+0). CONCLUSION: This score allows analysis of the global (cancer
      control and functional) results of radical prostatectomy and would facilitate
      comparisons between various surgical techniques (type of approach, nerve-sparing
      techniques) and various centres.

PMID- 14644119
TI  - Malignant non-urothelial neoplasms of the urinary bladder: a review.
AB  - OBJECTIVES: Non-urothelial bladder tumors frequently present a diagnostic and
      therapeutic challenge. We review the peer-reviewed literature to summarize the
      available evidence on the etiology, diagnosis and optimal management of malignant
      non-urothelial bladder tumors. METHODS: A comprehensive MEDLINE database search
      was performed. In addition, the proceedings of recent national and international
      urological and cancer society meetings were reviewed. RESULTS: Primary non
      urothelial bladder tumors are rare in Europe and North America representing less
      than 5% of all bladder lesions combined. A large number of risk factors have been
      implicated in the etiology of non-schistosomiasis-related squamous cell
      carcinoma, yet their exact pathomechanism remains poorly defined. Squamous cell
      carcinoma, adenocarcinoma, small cell carcinoma, sarcoma and
      carcinosarcoma/sarcomatoid tumors share an unfavorable prognosis despite
      aggressive surgical management that relates both to an aggressive biological
      behaviour as well as to an often times advanced stage at the time of diagnosis.
      Inflammatory pseudotumors are benign tumors of uncertain histogenesis that may
      mimic sarcomas. Paraganglioma, primary melanoma and lymphoma represent
      additional, exceedingly rare bladder tumors. CONCLUSIONS: The systematic
      investigation of most non-urothelial bladder tumors is limited by the rarity of
      these lesions. A concerted effort of multiple institutions linked together in a
      national or international tumor registry will be necessary to advance our
      understanding of these tumors, evaluate treatment strategies and optimize patient
      outcome in the future.

PMID- 14644120
TI  - Gemcitabine plus vinorelbine chemotherapy in patients with advanced bladder
      carcinoma who are medically unsuitable for or who have failed cisplatin-based
      chemotherapy.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of gemcitabine plus vinorelbine
      chemotherapy in patients with advanced bladder carcinoma who are unsuitable for
      or who have failed cisplatin-containing chemotherapy. PATIENTS AND METHODS:
      Thirty-one patients with advanced transitional cell carcinoma (TCC) of the
      bladder were scheduled to receive gemcitabine and vinorelbine chemotherapy.
      Twenty-one patients had received no prior chemotherapy and their creatinine
      clearance was below 50 ml/min (group 1), and the remaining 10 patients did not
      respond to previous cisplatin-containing chemotherapy (group 2). RESULTS: In
      group 1, objective response rate was 47.6%, including 2 (9.5%) complete and 8
      (38.9%) partial responses. In group 2, partial response was observed in 2 (20%)
      patients. The median survival time for patients in group 1 and 2 were 15 months
      (range 3-23) and 7 months (range 3-21), respectively. Grades 3 or 4 leukopenia
      developed in 16.1% of patients. Overall, 12.9% of the patients suffered from
      grade 3 nonhematologic toxicity. CONCLUSION: Our preliminary data indicate that
      the combination of gemcitabine and vinorelbine is active and well tolerated
      especially in patients with advanced TCC who are unsuitable for cisplatin-based
      chemotherapy.

PMID- 14644121
TI  - Comparison of telomerase activity and matrix metalloproteinase-9 in voided urine
      and bladder wash samples as a useful diagnostic tool for bladder cancer.
AB  - OBJECTIVES: This study was undertaken to evaluate the diagnostic efficacy of
      telomerase in urine, and bladder wash and also the matrix metalloproteinase-9
      (MMP-9) in urine, compared with voided urine cytology (VUC) and bladder wash
      cytology (BWC) for the detection of bladder cancer cells. MATERIAL AND METHODS: A
      total of 110 subjects provided a single preoperative voided morning urine sample
      for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash
      samples were obtained for telomerase and cytology. Cystoscopy was done for all
      patients as the reference standard for the identification of bladder cancer.
      Biopsy of any suspicious lesion was performed for histopathological examination.
      Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the
      remaining 16 had benign urological disorders. A group of 21 healthy volunteers
      were also enrolled in this study. RESULTS: The optimal threshold values for
      telomerase activity in urine, bladder wash and MMP-9 were calculated by receiver
      operator characteristics (ROC) curves as 0.05, 0.088 and 0.51 (ng/ml),
      respectively. The levels and the positivity rates of the 2 parameters were
      significantly higher in the malignant group compared to either the benign group
      or normal controls. Of the entire group, telomerase activity in urine, bladder
      wash, and MMP-9 were positive in 92%, 87% and 61%, respectively in bladder cancer
      patients with positive cytology. Moreover, these positive rates for them were
      significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%,
      respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall
      sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase
      activity in urine, and in bladder wash, respectively; 66.6% and 80% for MMP-9 and
      58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash
      cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher
      than either combined sensitivity of VUC with one of the biomarkers or than that
      of the biomarker alone. CONCLUSIONS: Our data indicate that urinary telomerase
      and MMP-9 had superior sensitivities over VUC. The combined use of markers
      increased the sensitivity of cytology from 58.46% to 95%. The higher
      sensitivities of markers in bilharzial bladder cancer than non-bilharzial type
      highlight their clinical utility in screening patients with urinary bilharziasis.

PMID- 14644122
TI  - Prostate-specific antigen as an estimator of prostate volume in the management of
      patients with symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVES: To assess the ability of serum prostate specific antigen (PSA) to
      estimate prostate volume (PV) to aid in the management of patients with benign
      prostatic hyperplasia (BPH). METHODS: From 1989 to 2002, data were collected from
      2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the
      Department of Urology of the University Medical Centre Nijmegen, The Netherlands.
      Baseline PV and serum PSA was determined using standard techniques. All patients
      who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml,
      were included. Patients with a history of prostate surgery, prostate cancer and
      conditions other than BPH at baseline were excluded. A log-transformed linear
      regression model was used to estimate PV. Receiver-operating characteristic (ROC)
      curves were constructed to evaluate the ability of serum PSA to estimate
      threshold PVs in men with BPH, and to select the optimal serum PSA cut-off
      values. RESULTS: The analyses included 1859 patients with a mean age of 63.5
      years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as
      well as serum PSA increases with age. Linear regression analyses showed that PV
      and serum PSA have an age-dependent log-linear relationship, where 42% of the
      variance of PV can be explained by PSA and age. ROC's area under the curves (AUC)
      reveal that PSA has a good predictive value for assessing 'prostate enlargement',
      with AUC around 82% in the overall age groups irrespective of the PV cut-off
      values. Optimal serum PSA cut-off values for the overall study population
      irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV
      >40 ml. CONCLUSIONS: This study suggests that serum PSA can estimate prostate
      enlargement sufficiently accurately to be useful for therapeutic, especially
      medical, management. It is well accepted that the outcome of pharmacotherapy for
      BPH depends on baseline PV. Therefore, in the absence of reliable direct
      measurement of PV, serum PSA determination may be used to optimise patient
      management.

PMID- 14644123
TI  - "Old-for-old" cadaveric renal transplantation: surgical findings, perioperative
      complications and outcome.
AB  - OBJECTIVE: To evaluate the surgical findings and outcome of locally allocated,
      blood-group-compatible but HLA-unmatched cadaveric kidneys in first renal
      transplantation of donor/recipient pairs aged 65 years and above (Eurotransplant
      Senior Program=ESP). METHODS: 26 patients of the study group (donor age 70.4 +/-
      3.6/recipient age 67.7 +/- 2.8) were compared to 30 controls aged 60 and above
      (mean recipient age 62.6 +/- 2.3/mean donor age 43.8 +/- 15.3). For controls
      kidney allocation included HLA matching. RESULTS: Cold ischemic time (ESP vs.
      controls 501 vs. 883 min; p<0.05) and mean number of HLA mismatches (4.2 +/- 1.36
      vs. 1.6 +/- 1.62; p<0.05) differed significantly. Delayed graft function was
      lower in the study group (12% vs. 43%; p<0.05), rejection episodes in the ESP
      group were numerous but did not differ significantly from the controls (46% vs.
      30%; p=0.21). More intraoperative complications and a higher incidence of donor
      organ arteriosclerosis (p<0.05) were seen in the ESP group. Three-year graft
      survival uncensored and censored for death with functioning graft did not differ,
      even though mean creatinine and creatinine clearance differed significantly
      beginning at month three. Three-year patient survival (55% vs. 81%) differed in
      favour of the control group, even though the difference was not significant due
      to small number of patients. CONCLUSION: "Old-for-old" kidney transplantation
      with local allocation yields graft survival rates comparable to HLA-matched young
      grafts and is a good approach to extend the donor and recipient pool. Careful
      patient selection is advised.

PMID- 14644124
TI  - Study on the prevalence and incidence of urolithiasis in Germany comparing the
      years 1979 vs. 2000.
AB  - OBJECTIVES: In 1979, we conducted a representative study to determine the
      prevalence and incidence of urolithiasis in Germany. Significant progress in
      stone therapy and changes in nutritional and environmental factors since then
      consequently led to a second study in 2001 under the same conditions as in 1979.
      METHODS: A representative sample of 7500 persons from all over Germany was
      questioned on the occurrence of urinary stones during their lifetimes
      (prevalence) and on acute urolithiasis in 2000 (incidence). Additionally, data
      were collected on urinary stone therapy and metaphylaxis. The current data were
      then compared with those from 1979. RESULTS: Prevalence has risen from 4% to 4.7%
      from 1979 to 2001. 9.7% of the 50-64 year old males in 2000 had already had
      urinary stones (females: 5.9%). The current recurrence rate of urinary stones was
      estimated to be 42%. In the year 2000, the incidence of urolithiasis in Germany
      was found to be 1.47% (1979: 0.54%). Over 40% of the stones were passed
      spontaneously. CONCLUSION: There has been a marked increase in the prevalence and
      incidence of urolithiasis in Germany within the last 22 years. This probably
      results from improvements in clinical-diagnostic procedures, changes in
      nutritional and environmental factors and a general apathy towards metabolic
      clarification and metaphylaxis.

PMID- 14644125
TI  - Comprehensive analysis of six years experience in tubularised incised plate
      urethroplasty and its extended application in primary and secondary hypospadias
      repair.
AB  - OBJECTIVE: We evaluated the potential of tubularised incised plate (TIP)
      urethroplasty in primary and secondary hypospadias repair focusing on the
      extended application of this procedure, the utility and handling of the urethral
      plate and operative results. METHODS: In this retrospective study, we analysed
      the medical records of 228 children with different levels of the hypospadiac
      meatus who underwent a TIP procedure between February 1997 and December 2002. The
      children were followed a mean of 42 months. Our medical records provided us with
      details about the location of the hypospadiac meatus, the width of the urethral
      plate before and after midline incision, primary versus secondary surgery,
      complications as well as notes on the extended application of the TIP procedure.
      RESULTS: The overall postoperative complication rate was 7.8%. The overall
      fistula rate was 5.7%, with 4.1% in primary distal, 9.6% in primary proximal and
      7.5% in secondary repair respectively. We had one case of meatal stenosis (0.4%)
      and one of urethral stricture (0.4%) and 3 cases of glandular dehiscence (1.3%).
      Due to the encouraging results, the frequency of TIP procedure in hypospadias
      surgery increased from 33% in 1997 to 82% in 2002. CONCLUSION: In our study the
      TIP procedure has emerged as the first-choice technique in primary hypospadias
      repair--irrespective of the level of the hypospadiac meatus and the width of the
      original urethral plate. This procedure has also proved to be favourable for many
      cases at secondary surgery.

PMID- 14644127
TI  - Novel surgical technique for the treatment of female stress urinary incontinence:
      transobturator vaginal tape inside-out.
AB  - OBJECTIVES: To describe a new, simple surgical technique for the treatment of
      female stress urinary incontinence (SUI) and to evaluate its feasibility.
      METHODS: We have developed a novel surgical treatment of SUI, the transobturator
      inside-out tension-free urethral suspension, which uses specifically designed
      surgical tools, and in which a synthetic tape is passed from underneath the
      urethra, through the obturator foramens, towards the thigh folds, without
      entering the pelvic region at any time during the procedure. The tape is
      positioned without tension under the junction between mid and distal urethra.
      RESULTS: The procedure was carried out in 107 consecutive patients (mean age: 62
      years) using the same operative protocol in all case subjects, independently of
      the patient's size and weight. Mean operative time was 14 min (range: 7-20) in
      case of isolated SUI treatment. No bladder or urethral injuries and no vascular
      (hematoma or bleeding) or neurological complications were encountered.
      CONCLUSIONS: The results of this study indicate that our novel transobturator
      inside-out surgical technique for treating SUI is feasible, accurate, and quick.
      This technique avoids damage to the urethra and bladder and, therefore, makes
      cystoscopy not necessary. Further prospective studies are currently ongoing to
      determine the efficacy of our new surgical approach for treating SUI.

PMID- 14644126
TI  - Penile corporoplasty using tunica albuginea free graft from proximal corpus
      cavernosum: a new technique for treatment of penile curvature in Peyronie's
      disease.
AB  - OBJECTIVES: In Peyronie's disease, any kind of plication technique for correcting
      penile deformities is associated with penile shortening in addition to the
      disease-related shrinkage. To minimize penile shortening we describe a new
      technique of penile corporoplasty using a free graft from the tunica albuginea.
      PATIENTS AND METHODS: From October 2001 to February 2003 we treated 18 patients
      with the new technique. All patients had stable Peyronie's disease with relevant
      curvature and sufficient erectile rigidity without any signs of inflammatory
      disease. Penile corporoplasty was performed by incision of the plaques to produce
      straightening. The resulting gap was covered with a free graft of tunica
      albuginea removed from the crural segment of the corpora cavernosa. RESULTS: In a
      preliminary follow-up of 16 patients, 12 penises were straight and 4 had a
      residual curvature less than 20 degrees. Two patients needed sildenafil for
      sufficient penile rigidity. Fourteen of 16 patients were satisfactory with the
      result of penile straightening. No severe perioperative complication was noted.
      CONCLUSION: The technique of penile straightening using a free tunica albuginea
      graft is effective and avoids additional shortening of the penis. As the results
      are preliminary, the study is continued to gain experience with a larger number
      of patients.

PMID- 14644128
TI  - Pro-erectile effect of vardenafil: in vitro experiments in rabbits and in vivo
      comparison with sildenafil in rats.
AB  - OBJECTIVES: To assess pro-erectile responses to vardenafil, a new selective PDE5
      inhibitor, in vitro in isolated rabbit corpora cavernosa, and in vivo in
      anaesthetized rats. METHODS: Rabbit cavernosal strips were precontracted with 10
      microM phenylephrine. Dose-response relaxation curves to cumulative dosings of
      vardenafil (1 nM-10 microM) were constructed alone and in the presence of 10 mM L
      NAME. Relaxation responses to electrical field stimulation (EFS) (2 Hz, 2 ms, 10
      V) were compared in control preparations and in the presence of vardenafil (1-10
      nM). Male Sprague-Dawley rats were anaesthetized with urethane and prepared for
      measurement of blood pressure and intracavernous pressure. Erectile responses
      (ICPmax/dBP x 100) to cavernous nerve submaximal stimulation (10 Hz, 1 ms, 0.45
      1.6 V) were determined before, and 3, 10 and 23 min after i.v. administration of
      saline, vardenafil or sildenafil (0.1, 1 mg/kg). RESULTS: Vardenafil was
      effective in relaxing precontracted rabbit cavernosal strips (IC50 54 +/- 18 nM).
      This relaxing activity was partially antagonized with 10 mM L-NAME, increasing
      the IC50 to 620 +/- 81 nM. Vardenafil significantly increased (more than 4 times)
      relaxation of precontracted rabbit cavernosal strips to EFS at 10 nM. In
      anaesthetized rats, erectile responses were significantly facilitated 3 and 13
      min after 0.1 and 1 mg/kg vardenafil was administered. In contrast, 1 mg/kg
      sildenafil only significantly increased erectile responses at 3 min post
      injection. CONCLUSIONS: Vardenafil relaxes rabbit corpus cavernosum in vitro and
      is effective at a lower dose than sildenafil in facilitating erectile responses
      to cavernous nerve stimulation in anaesthetized rats.

PMID- 14644129
TI  - Amiloride and urinary trypsin inhibitor inhibit urothelial cancer invasion.
AB  - OBJECTIVE: To determine the contribution of urokinase-type plasminogen activator
      (uPA) and plasmin in the invasion of highly invasive urothelial cancer cells.
      METHODS: We compared expression levels of mRNA and protease activity of uPA and
      plasmin formation in primary cultures of the noninvasive transitional cell
      carcinoma, UCT-1, and in the highly invasive type, UCT-2. By using in vitro cell
      invasion assay system, we evaluated the effects of amiloride and urinary trypsin
      inhibitor (UTI), which inhibit uPA and plasmin, respectively, on invasion by both
      cell lines. RESULTS: Expression levels of mRNA, protein, and activities of uPA
      were significantly higher (p<0.005) and resulted in more plasminogen activation
      in UCT-2 than in UCT-1. Amiloride and UTI significantly inhibited plasmin
      formation and the invasion of both cell lines (p<0.001). CONCLUSIONS: High
      expression levels of mRNA, activities of uPA and high plasmin formation
      significantly potentiated the invasiveness of urothelial cancer cells. Thus,
      inhibitors of uPA and plasmin, such as amiloride and UTI, respectively, could be
      useful therapeutic tools with which to treat urothelial cancer.

PMID- 14644130
TI  - Down-regulation of estrogen receptor beta and transcriptional coregulator
      SNURF/RNF4 in testicular germ cell cancer.
AB  - OBJECTIVE: The role of estrogens and androgens in the etiology and progression of
      testicular germ cell cancer is poorly understood. To gain insight into the role
      of sex steroid action in testicular tumorigenesis, we have measured mRNAs
      encoding estrogen receptor beta (ERbeta), androgen receptor (AR), and their
      coregulators SNURF/RNF4, PIASx, and PIAS1 in testicular germ cell tumors.
      METHODS: We used real-time quantitative reverse transcription-PCR assay to
      compare the steroid receptor and coregulator mRNA levels in 12 matched samples of
      testicular tumors and adjacent normal tissues (seminomas n=8, nonseminomas n=4).
      In addition, ERbeta and SNURF/RNF4 protein immunoreactivity was analyzed from
      paraffin-embedded normal testis and tumor specimens. RESULTS: ERbeta mRNA levels
      were down-regulated by 59% in seminomas (p=0.017), and those of AR and SNURF/RNF4
      mRNAs were decreased by 75% and 67%, respectively, in seminomas and
      teratocarcinomas compared to paired normal samples (p=0.034 for both, Wilcoxon
      signed rank test), whereas the PIASx and PIAS1 mRNA were unaltered. ERbeta and
      SNURF/RNF4 were also clearly down-regulated at the protein level in testicular
      tumors. CONCLUSIONS: Expression of ERbeta and SNURF/RNF4 was significantly lower
      in cancerous than in noncancerous testis tissue. Down-regulation of the ERbeta
      and the coregulator SNURF/RNF4 genes may play a role in testicular tumorigenesis.

PMID- 14644131
TI  - LAG-3: a regulator of T-cell and DC responses and its use in therapeutic
      vaccination.
AB  - The function mediated by the engagement of the lymphocyte activation gene-3 (LAG
      3, CD223) receptor expressed on activated T cells by its MHC class II ligand has
      remained enigmatic, partly owing to discrepancies between published results in
      human and mouse systems. Recent studies in mice have reconciled previous
      interpretations and clearly show that, as in human cells, LAG-3 negatively
      regulates T-cell function and homeostasis. As a soluble molecule, LAG-3 activates
      antigen-presenting cells through MHC class II signalling, leading to increased
      antigen-specific T-cell responses in vivo.

PMID- 14644132
TI  - Absence of S100A12 in mouse: implications for RAGE-S100A12 interaction.

PMID- 14644133
TI  - TCR triggering: co-receptor-dependent or -independent?

PMID- 14644135
TI  - The search for the CD8+ cell anti-HIV factor (CAF).
AB  - Efforts to control HIV infection have led to the development of several
      antiretroviral drugs that can limit virus replication, however, these therapies
      do not offer a long-term solution to the infection. We can learn a great deal
      from HIV-infected individuals who have lived for more than ten years and remain
      healthy without receiving antiviral drugs. These long-term survivors or long-term
      non-progressors have an immune system that can control HIV infection. A major
      component of this immune response is innate immunity, particularly the CD8(+)
      cell antiviral non-cytotoxic response (CNAR), mediated by a novel CD8(+) cell
      antiviral factor (CAF). The characteristics of CNAR and CAF will be described and
      progress made toward identifying CAF will be reviewed. These studies have
      uncovered several potentially important natural anti-HIV factors and their
      relationship to the originally described CAF is considered.

PMID- 14644136
TI  - Regulation of T-cell functions by MHC class II self-presentation.
AB  - The role of MHC class II in the control of T-cell responses to self and foreign
      antigens is still unclear. No unifying principle yet explains how class II
      molecules repress immunity to self or allogeneic antigens. Our recent data in a
      model of tolerance to allogeneic grafts, probably induced by allele-specific
      class II peptides, suggest that it is by presenting themselves [class II
      peptide(s) docked on self class II, in a complex we have named T-Lo] that class
      II controls T-cell activity. The engagement of the regulatory T (T-reg)-cell T
      cell receptor (TCR) with self T-Lo would explain the beneficial effect of donor
      recipient class II matching in clinical transplantation, the correlation between
      T-cell suppression and class II, and the altered T-reg-cell functions observed in
      class II-dependent autoimmune pathologies.

PMID- 14644137
TI  - Fatty acids as gatekeepers of immune cell regulation.
AB  - Fatty acids have diverse roles in all cells. They are important as a source of
      energy, as structural components of cell membranes, as signalling molecules and
      as precursors for the synthesis of eicosanoids. Recent research has suggested
      that the organization of fatty acids into distinct cellular pools has a
      particularly important role in cells of the immune system and that forms of lipid
      trafficking exist, which are as yet poorly understood. This Review examines the
      nature and regulation of cellular lipid pools in the immune system, their
      delivery of fatty acids or fatty acid derivatives to specific locations and their
      potential role in health and disease.

PMID- 14644138
TI  - Induction of tolerogenic DCs: 'you are what you eat'.
AB  - Dendritic cells (DCs) take up antigens using antigen receptors that can be
      divided into three major classes: C-type lectins, integrins and Fc receptors.
      These receptors facilitate effective presentation of MHC-peptide complexes to T
      cells, resulting in the induction of immune responses. However, we discuss recent
      evidence that some receptors also cause induction of tolerance. Signaling motifs
      within the receptors either block maturation of DCs or induce signals that render
      DCs tolerogenic. These DCs then either induce regulatory T cells or cause
      deletion of effector T cells, resulting in the induction of tolerance. Antigen
      receptors expressed by DCs might therefore have an important role in the
      induction and maintenance of peripheral tolerance.

PMID- 14644139
TI  - Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial
      sensing.
AB  - Nod2 (Card15) belongs to the family of the recently described Nod molecules,
      which also includes the closely related protein Nod1 (Card4). Nod proteins have
      been initially described as intracellular activators of the caspase and NF-kappaB
      signaling pathways. Recent progress has enabled research to demonstrate
      genetically that NOD2 (CARD15) is involved in the predisposition to Crohn's
      disease and Blau syndrome. In addition, biochemical evidence has unraveled the
      role of Nod1 (Card4) and Nod2 (Card15) as intracellular sensors of bacterial
      peptidoglycan. Together, studies on Nod2 (Card15) provide a conceptual link
      between inflammatory disorders, such as Crohn's disease and Blau syndrome, and
      bacterial sensing.

PMID- 14644140
TI  - Regulation of cytokine signaling by SOCS family molecules.
AB  - Cytokine signaling is dependent on the activation of intracellular molecules,
      including JAKs (Janus family kinases) and STATs (signal transducers and
      activators of transcription). Since the discovery of the SOCS (suppressor of
      cytokine signaling) family molecules in 1997, extensive investigation of these
      molecules has given important insights into the as yet unclarified regulatory
      mechanisms of cytokine signaling. Recent gene targeting analyses of SOCS
      molecules have revealed that they do indeed have essential roles in vivo (more
      specific than those expected from overexpression studies in vitro) in the
      negative regulation of various cytokines. Moreover, consistent with the
      pathological actions of cytokines in human diseases, recent lines of evidence
      also indicate that SOCS molecules are implicated in autoimmunity, allergy and
      cancers.

PMID- 14644141
TI  - Towards in silico prediction of immunogenic epitopes.
AB  - As torrents of new data now emerge from microbial genomics, bioinformatic
      prediction of immunogenic epitopes remains challenging but vital. In silico
      methods often produce paradoxically inconsistent results: good prediction rates
      on certain test sets but not others. The inherent complexity of immune
      presentation and recognition processes complicates epitope prediction. Two
      encouraging developments - data driven artificial intelligence sequence-based
      methods for epitope prediction and molecular modeling methods based on three
      dimensional protein structures - offer hope for the future.

PMID- 14644143
TI  - A deformable digital brain atlas system according to Talairach and Tournoux.
AB  - Brain atlases are valuable tools which assist neurosurgeons during the planning
      of an intervention. Since a printed atlas book has several disadvantages-among
      them the difficulty to map the information onto a patient's individual anatomy-we
      have developed a digital version of the well-established stereotaxic brain atlas
      of Talairach and Tournoux. Our atlas system is mainly dedicated to assist
      neurosurgical planning, and its benefits are: (i) a three-dimensional (3D)
      representation of most brain structures contained in the Talairach atlas; (ii) a
      nonrigid matching capability which warps the standard atlas anatomy to an
      individual brain magnetic resonance imaging (MRI) dataset in a few minutes and
      which is able to take deformations due to tumors into account; (iii) the
      integration of several sources of neuroanatomical knowledge; (iv) an interface to
      a navigation system which allows utilization of atlas information
      intraoperatively. In this paper we outline the algorithm we have developed to
      achieve 3D surface models of the brain structures. Moreover, we describe the
      nonrigid matching method which consists of two tasks: firstly, point
      correspondences between the atlas and the patient are established in an automatic
      fashion, and secondly these displacement vectors are interpolated using a radial
      basis function approach to form a continuous transformation function. To generate
      appropriate target structures for the first of these tasks, we implemented a
      quick segmentation tool which is capable to segment the cortex and ventricles in
      less than 5 min. An evaluation shows that our nonrigid approach is more precise
      than the conventional piecewise linear matching, though it should be further
      improved for the region around the deep grey nuclei. Summarizing, we developed a
      Win32 program which permits the convenient and fast application of standardized
      anatomy to individual brains which potentially contain tumors.

PMID- 14644144
TI  - Modelling of interaction between a spatula and a human brain.
AB  - This paper describes a method for surgery simulation, or more specifically a
      learning system of how to use a brain spatula. Improper use of brain spatulas can
      lead to brain tissue lesions such as tearing of brain tissue and ischemia. The
      idea is to provide surgeons with a tool which can teach them the correlation
      between deformation and applied force. The system includes a Finite Element based
      model of the brain in a Virtual Reality setup with haptic feedback. The physical
      model links the shape of the deformable model with the associated force. The
      interaction between the spatula and the brain model is handled by a collision
      response method which aims at smoothing the discrete haptic feedback. The
      experimental results are promising even though the used force feedback device is
      somewhat constraining the realism.

PMID- 14644145
TI  - Interactive 3D editing tools for image segmentation.
AB  - Segmentation is an important part of image processing, which often has a large
      impact on quantitative image analysis results. Fully automated operator
      independent segmentation procedures that successfully work in a population with a
      larger biological variation are extremely difficult to design and usually some
      kind of operator intervention is required, at least in pathological cases. We
      developed a variety of 3D editing tools that can be used to correct or improve
      results of initial automatic segmentation procedures. Specifically we will
      discuss and show examples for three types of editing tools that we termed: hole
      filling (tool 1), point-bridging (tool 2), and surface-dragging (tool 3). Each
      tool comes in a number of flavors, all of which are implemented in a truly 3D
      manner. We describe the principles, evaluate efficiency and flexibility, and
      discuss advantages and disadvantages of each tool. We further demonstrate the
      superiority of the 3D approach over the time-consuming slice-by-slice editing of
      3D datasets, which is still widely used in medical image processing today. We
      conclude that performance criteria for automatic segmentation algorithms may be
      eased significantly by including 3D editing tools early in the design process.

PMID- 14644146
TI  - Diffusion tensor magnetic resonance image regularization.
AB  - As multi-dimensional complex data become more common, new regularization schemes
      tailored to those data are needed. In this paper we present a scheme for
      regularising diffusion tensor magnetic resonance (DT-MR) data, and more generally
      multi-dimensional data defined by a direction map and one or several magnitude
      maps. The scheme is divided in two steps. First, a variational method is proposed
      to restore direction fields with preservation of discontinuities. Its theoretical
      aspects are presented, as well as its application to the direction field that
      defines the main orientation of the diffusion tensors. The second step makes use
      of an anisotropic diffusion process to regularize the magnitude maps. The main
      idea is that for a range of data it is possible to use the restored direction as
      a prior to drive the regularization process in a way that preserves
      discontinuities and respects the local coherence of the magnitude map. We show
      that anisotropic diffusion is a convenient framework to implement that idea, and
      define a regularization process for the magnitude maps from our DT-MR data. Both
      steps are illustated on synthetic and real diffusion tensor magnetic resonance
      data.

PMID- 14644147
TI  - The application of serial MRI analysis techniques to the study of cerebral
      atrophy in late-onset dementia.
AB  - We have used a serial MR image analysis technique previously developed for
      studies of cerebral atrophy in early-onset dementia and applied it to a study of
      late-onset dementia patients with images acquired using a different scanner and
      scan sequence. Validation and optimisation tests showed that with only small
      changes to key analysis parameters the technique can successfully be applied to
      previously untested data with dissimilar image characteristics. The overall
      accuracy in estimation of cerebral atrophy using the technique was determined to
      be between 2 and 4 ml (1sigma) depending on the conditions during image
      acquisition. By comparing the results of alternative registration techniques we
      demonstrate the potential of using of fully automated 9 DOF image registration as
      an effective and efficient means of correcting for scanner pixel size variations,
      even in the presence of significant cerebral atrophy. Applied to the late-onset
      dementia study, patients were found to have significantly increased mean atrophy
      rates (p<0.001) compared to controls. In general the analysis technique is shown
      to be a robust, accurate and transferable tool of potential value for future
      studies of dementia and related neuro-degenerative disorders.

PMID- 14644148
TI  - Registration of freehand 3D ultrasound and magnetic resonance liver images.
AB  - We present a method to register a preoperative MR volume to a sparse set of
      intraoperative ultrasound slices. Our aim is to allow the transfer of information
      from preoperative modalities to intraoperative ultrasound images to aid needle
      placement during thermal ablation of liver metastases. The spatial relationship
      between ultrasound slices is obtained by tracking the probe using a Polaris
      optical tracking system. Images are acquired at maximum exhalation and we assume
      the validity of the rigid body transformation. An initial registration is carried
      out by picking a single corresponding point in both modalities. Our strategy is
      to interpret both sets of images in an automated pre-processing step to produce
      evidence or probabilities of corresponding structure as a pixel or voxel map. The
      registration algorithm converts the intensity values of the MR and ultrasound
      images into vessel probability values. The registration is then carried out
      between the vessel probability images. Results are compared to a "bronze
      standard" registration which is calculated using a manual point/line picking
      algorithm and verified using visual inspection. Results show that our starting
      estimate is within a root mean square target registration error (calculated over
      the whole liver) of 15.4 mm to the "bronze standard" and this is improved to 3.6
      mm after running the intensity-based algorithm.

PMID- 14644149
TI  - The impact of FISH on globin gene regulation research.
AB  - The alpha- and beta-globin gene clusters are subject to several levels of
      regulation leading to differentiation and developmental stage-specific
      expression. Not only the interaction of cis-acting elements and cell-specific
      trans-acting factors but also the chromosomal environment, nuclear
      compartmentalization of genome regions, and transcription factors play important
      roles in globin gene regulation research. FISH, with a refined technique and an
      incorporation of other molecular techniques, has become a powerful technique in
      gene regulation research, particular for the analysis of replication timing and
      primary transcripts as well as the research of the special organization of large
      scale chromatin domains and nuclear compartmentalization at cellular and
      subcellular levels. This review will focus on the major impact of FISH on globin
      gene regulation research at different regulation levels, such as replicating
      timing, gene transcription, nuclear relocation, and chromosomal position effect.

PMID- 14644150
TI  - On and off: proteasome and TGF-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) signaling mainly relies on the TGF
      beta receptor-Smad pathway. Meanwhile, TGF-beta binding to its receptors
      initiates the degradation of several key components of its signaling pathway. The
      degradation of these components, including both positive and negative
      transducers, is mediated by the ubiquitin-proteasome system. Inhibition of the
      proteasome activity causes accumulation of these components in the cells and
      modulates TGF-beta signaling in a time-dependent and gene-specific manner. The
      accelerated degradation of TGF-beta signaling components via the proteasome
      system has been found in a number of tumors, indicating that dysregulated
      proteasomal degradation is a novel pathway how tumor cells silence TGF-beta
      signaling.

PMID- 14644151
TI  - Cell differentiation and proliferation--simultaneous but independent?
AB  - Despite studies over many years, it is still not clear to what extent cellular
      controls on proliferation and on differentiation are interrelated. For example,
      the idea that exit from cell cycle into G1/G0 is a necessary-or at least frequent
      prelude to differentiation developed partly from studies of haemopoietic cell
      maturation, often using cell lines as models. The responses of cells to treatment
      with differentiating agents suggested that exit from cell cycle into G1/G0 occurs
      quite quickly, with functional differentiated characteristics acquired later, and
      so promoted the notion that cyclin-dependent kinase inhibitors (CDKIs) might be
      important initiators of normal differentiation. However, recent work has made it
      clear that differentiation and cell proliferation are regulated simultaneously
      but independently, that cells often start differentiating long before they stop
      dividing, and that the launching of differentiation is not restricted to any
      particular segment of the cell cycle. This combination of attributes allows
      expansion of cell numbers and acquisition of differentiated function to occur in
      parallel, generating abundant effector cells. Given this dichotomy, future
      studies to develop a more exact picture of the events that initiate and drive
      differentiation might be simplified by studying differentiation under
      experimental conditions that divorce it from concerns about cell cycle control.

PMID- 14644152
TI  - Intracellular zinc fluctuations modulate protein tyrosine phosphatase activity in
      insulin/insulin-like growth factor-1 signaling.
AB  - Zinc is an effector of insulin/IGF-1 signaling and has insulinomimetic effects,
      the molecular basis of which is not understood. The present study establishes the
      capacity of zinc to inhibit protein tyrosine phosphatases (PTPs) as a cause for
      these effects and, moreover, demonstrates modulation of the insulin response by
      changes in intracellular zinc. The inhibition of PTPs by zinc occurs at
      significantly lower concentrations than previously reported. In vitro, zinc
      inhibits PTPs 1B and SHP-1 with IC(50) values of 17 and 93 nM, respectively. A
      fluorescent probe with a similar binding constant [FluoZin-3, K(D)(Zn) = 15 nM]
      detects corresponding concentrations of zinc within cells. Increase of cellular
      zinc after incubation with both zinc and the ionophore pyrithione augments
      protein tyrosine phosphorylation, and in particular the phosphorylation of three
      activating tyrosine residues of the insulin/IGF-1 receptor. Vice versa, specific
      chelation of cellular zinc with the membrane-permeable N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine suppresses insulin- and IGF-1-stimulated
      phosphorylation. In the context of the emerging concept that intracellular zinc
      is tightly regulated and fluctuates dynamically, these results suggest that a
      pool of cellular zinc modulates phosphorylation signaling.

PMID- 14644153
TI  - Mutants of the protein serine kinase PSKH1 disassemble the Golgi apparatus.
AB  - We have dissected the molecular determinants involved in targeting the protein
      serine kinase PSKH1 to the endoplasmic reticulum (ER), the Golgi apparatus, and
      the plasma membrane (PM). Given this intracellular localization pattern, a
      potential role of PSKH1 in the secretory pathway was explored. The amino-terminal
      of PSKH1 revealed a striking similarity to the often acylated Src homology domain
      4 (SH4)-harboring nonreceptor tyrosine kinases. Biochemical studies demonstrated
      that PSKH1 is myristoylated on glycine 2 and palmitoylated on cysteine 3. Dual
      amino-terminal acylation targets PSKH1 to Golgi as shown by colocalization with
      beta-COP and GM130, while nonpalmitoylated (myristoylated only) PSKH1 targets
      intracellular membranes colocalizing with protein disulphide isomerase (PDI, a
      marker for ER). Immunoelectron microscopy revealed that the dually acylated amino
      terminal domain (in fusion with EGFP) was targeted to Golgi membranes as well as
      to the plasma membrane (PM), suggesting that the amino-terminal domain provides
      PSKH1 with membrane specificity dependent on its fatty acylation status.
      Subcellular fractionation by sucrose gradient analysis confirmed the impact of
      dual fatty acylation on endomembrane targeting, while cytosol and membrane
      fractioning revealed that myristoylation but not palmitoylation was required for
      general membrane association. A minimal region required for proper Golgi
      targeting of PSKH1 was identified within the first 29 amino acids. Expression of
      a PSKH1 mutant where the COOH-terminal kinase domain was swapped with green
      fluorescent protein and cysteine 3 was exchanged with serine resulted in
      disassembly of the Golgi apparatus as visualized by redistribution of beta-COP
      and GM130 to a diffuse cytoplasmic pattern, while leaving the tubulin skeleton
      intact. Our results suggest a structural and regulatory role of PSKH1 in
      maintenance of the Golgi apparatus, a key organelle within the secretory pathway.

PMID- 14644154
TI  - Antisense oligonucleotides reach mRNA targets via the RNA matrix: downregulation
      of the 5-HT1A receptor.
AB  - Successful application of antisense oligonucleotides (ODNs) in cell biology and
      therapy will depend on the ease of design, efficiency of (intra)cellular
      delivery, ODN stability, and target specificity. Equally essential is a detailed
      understanding of the mechanism of antisense action. To address these issues, we
      employed phosphorothioate ODNs directed against specific regions of the mRNA of
      the serotonin 5HT1A receptor, governed by sequence and structure. We demonstrate
      that rather than various intracellular factors, the gene sequence per se
      primarily determines the antisense effect, since 5HT1a autoreceptors expressed in
      RN46A cells, postsynaptic receptors expressed in SN48 cells, and receptors
      overexpressed in LLP-K1 cells are all efficiently downregulated following ODN
      delivery via a cationic lipid delivery system. The data also reveal that the
      delivery system as such is a relevant parameter in ODN delivery. Antisense ODNs
      bound extensively to the RNA matrix in the cell nuclei, thereby interacting with
      target mRNA and causing its subsequent degradation. Antisense delivery
      effectively diminished the mRNA pool, thus resulting in downregulation of newly
      synthesized 5HT1A proteins, without the appearance of truncated protein
      fragments. In conjunction with the selected mRNA target sequences of the ODNs,
      the latter data indicated that effective degradation rather than a steric
      blockage of the mRNA impedes protein expression. The specificity of the antisense
      approach, as described in this study, is reflected by the effective functional
      downregulation of the 5-HT1A receptor.

PMID- 14644155
TI  - Alternative pathway for the role of furin in tumor cell invasion process.
      Enhanced MMP-2 levels through bioactive TGFbeta.
AB  - The mammalian convertase furin plays a significant role in tumorigenesis and its
      overexpression was observed in a number of different cancer types. To date,
      however, few mechanisms of action have been described. Most of the information
      available concerns the invasion step and designates MT1-MMP, through the
      activation of MMP-2, as the bona fide substrate mediating furin activity.
      However, recent reports indicate furin-independent pathways for MT1-MMP
      activation. To gain further insights into the role of furin in the invasion
      process, we studied the in vitro invasive capacity of LoVo cells, a furin
      deficient adenocarcinoma cell line transfected with wild-type furin. Furin
      complementation resulted in an increased cell invasiveness that correlated with
      their capacity to produce MMP-2. Chemical blockage of MMPs activity with BB-3103
      or MMP-2-specific antibodies revealed that the increased invasive capacity of
      furin-complemented cells was mediated by MMP-2. Unexpectedly, furin
      complementation did not change the status of MT1-MMP expression or activation,
      but instead resulted in the production of mature and bioactive TGFbeta1. Western
      blot-analysis of TGFbeta1 fragmentation species indicated that TGFbeta maturation
      step required furin activity, whereas results from TGFbeta-inducible reporter
      assays in the presence of MMP inhibitors or exogenous MMP-2 suggested that the
      activation step was under MMP influence. In addition, blockage with TGFbeta
      neutralizing antibodies revealed that furin-induced invasiveness was mediated by
      endogenous production of TGFbeta. Taken together, our findings established the
      existence of a novel alternative/complementary pathway by which furin increases
      tumor cell invasion through an amplification/activation loop between MMP-2 and
      TGFbeta.

PMID- 14644156
TI  - Identification of opioid-regulated genes in human lymphocytic cells by
      differential display: upregulation of Kruppel-like factor 7 by morphine.
AB  - Morphine was previously found to compromise the chemotactic mobility of
      leukocytic cells toward inflammatory sites as well as induce the expression of
      chemokine receptor CCR5, a coreceptor for HIV entry, on lymphocytes. Both effects
      increase the host's susceptibility for HIV infection. In this report, we used a
      reverse transcription-polymerase chain reaction-based differential display (RT
      PCR DD), an RNA finger printing procedure, coupled with Northern slot blot
      hybridization, in identifying gene or genes regulated by morphine in human
      lymphocytic cells. Ten positive gene segments, including two morphine
      downregulated genes and eight morphine upregulated genes, were identified.
      Analysis of the DNA sequences of these gene segments showed high homologies to
      known DNA and protein sequences on databases, of which two apoptosis/cell growth
      related genes (PNAS-133 and Kruppel-like factor 7) were revealed. PNAS-133 gene
      was downregulated by morphine whereas the Kruppel-like factor 7 (KLF7), a zinc
      finger transcription factor, was upregulated by morphine. The upregulation of
      KLF7 by morphine was further studied and found to be at both the transcriptional
      and the translational levels in a naloxone-reversible manner. Cell growth was
      promoted by morphine up to day 4 (72 h) post treatment. These findings suggest a
      unique role for morphine in regulating cell proliferation and differentiation of
      immune cells.

PMID- 14644157
TI  - Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying
      nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene.
AB  - Mutations in the LMNA gene encoding nuclear lamins A and C are responsible for
      seven inherited disorders affecting specific tissues. We have analyzed skin
      fibroblasts from a patient with type 1B limb-girdle muscular dystrophy and from
      her deceased newborn grandchild carrying, respectively, a heterozygous (+/mut)
      and a homozygous (mut/mut) nonsense Y259X mutation. In fibroblasts(+/mut), the
      presence of only 50% lamins A and C promotes no detectable abnormality, whereas
      in fibroblasts(mut/mut) the complete absence of lamins A and C leads to
      abnormally shaped nuclei with lobules in which none of the analyzed nuclear
      proteins were detected, i.e., B-type lamins, emerin, nesprin-1alpha, LAP2beta,
      and Nup153. These lobules perturb cell division as fibroblast(mut/mut) cultures
      with large proportions of cells with dysmorphic nuclei grow more slowly than
      controls and the cell proliferation normalizes when the number of these
      abnormally shaped nuclei declines. In all fibroblasts(mut/mut), nesprin-1alpha
      like emerin exhibited aberrant localization in the endoplasmic reticulum.
      Transfection of wild-type lamin A or C cDNAs restored the correct localization of
      both emerin and nesprin-1alpha. These data demonstrate that lamin C, like lamin
      A, interacts in vivo directly with nesprin-1alpha and with emerin and that lamin
      A or C is sufficient for the correct anchorage of emerin and nesprin-1alpha at
      the nuclear envelope in human cells.

PMID- 14644158
TI  - RhoA induces MMP-9 expression at CD44 lamellipodial focal complexes and promotes
      HMEC-1 cell invasion.
AB  - Much progress has been made in recent years in the understanding of angiogenesis,
      yet signalling pathways involved remain poorly defined. Here we report that small
      RhoA GTPase is implicated in the invasion of human microvascular endothelial
      cells (HMEC-1). Ectopic expression of active-RhoA GTPase induced the expression
      of MMP-9 metalloproteinase, a key proteinase of the basement membrane, and
      promoted migration of endothelial cells through a 3D-matrix protein gel. MMP-9
      was either directed as vesicular-like patches to the apical side of cells, or
      addressed to specific membrane sites at the cell surface. Confocal microscopy
      analyses indeed revealed clustering of MMP-9 in advancing lamellipodia at the
      forefront of endothelial cells, where this proteinase colocalized with RhoA and
      CD44, a transmembrane receptor known to be proteolysed in tumor cell progression.
      In addition, TIMP-1, a natural MMP inhibitor, significantly reduced the invasion
      of RhoAV14 expressing cells, suggesting that MMP-9 was a critical
      metalloproteinase responsible, at least partly, for the RhoAV14-induced
      endothelial cell invasion. We propose that RhoA triggers signalling pathways
      that, upregulating expression of a proteinase at specific membrane localizations,
      may confer an highly invasive phenotype to endothelial cells.

PMID- 14644159
TI  - Endosomal trafficking of the Menkes copper ATPase ATP7A is mediated by vesicles
      containing the Rab7 and Rab5 GTPase proteins.
AB  - The Cu-ATPase ATP7A (MNK) is localized in the trans-Golgi network (TGN) and
      relocalizes in the plasma membrane via vesicle-mediated traffic following
      exposure of the cells to high concentrations of copper. Rab proteins are
      organelle-specific GTPases, markers of different endosomal compartments; their
      role has been recently reviewed (Trends Cell Biol. 11(2001) 487). In this article
      we analyze the endosomal pathway of trafficking of the MNK protein in stably
      transfected clones of CHO cells, expressing chimeric Rab5-myc or Rab7-myc
      proteins, markers of early or late endosome compartments, respectively. We
      demonstrate by immunofluorescence and confocal and electron microscopy techniques
      that the increase in the concentration of copper in the medium (189 microM)
      rapidly induces a redistribution of the MNK protein from early sorting endosomes,
      positive for Rab5-myc protein, to late endosomes, containing the Rab7-myc
      protein. Cell fractionation experiments confirm these results; i.e., the MNK
      protein is recruited to the endosomal fraction on copper stimulation and
      colocalizes with Rab5 and Rab7 proteins. These findings allow the first
      characterization of the vesicles involved in the intracellular routing of the MNK
      protein from the TGN to the plasma membrane, a key mechanism allowing appropriate
      efflux of copper in cells grown in high concentrations of the metal.

PMID- 14644160
TI  - The antioxidant, rather than prooxidant, activities of quercetin on normal cells:
      quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis.
AB  - The bioflavonoid quercetin is a dietary anticancer chemical that is capable of
      inducing apoptosis in tumor cells. Although the activity of quercetin is believed
      to be due to its antioxidative properties, it has recently been suggested that
      quercetin also has prooxidant activities, which might effect cytotoxicity
      directly. In this study, we used mouse thymocytes to investigate whether
      quercetin behaved as a protector against oxidative stress or as a cytotoxic
      agent. Quercetin treatment did not induce oxidative damage, but protected mouse
      thymocytes from glucose oxidase (GO)-mediated apoptosis in a dose-dependent
      manner. Furthermore, electrophoretic mobility shift assays revealed that
      quercetin (50 microM) treatment suppressed the GO-mediated DNA binding activity
      of redox state-sensitive transcription factors, such as NF-kappaB, AP-1, and p53.
      This result suggests that quercetin has antioxidative effects on thymocytes. More
      interestingly, quercetin treatment alone (50 microM) increased the DNA-binding
      activity of AP-1, which consisted of heterodimer of c-Jun and Fra-2. Finally, the
      antioxidant activity of quercetin was confirmed using a cell-free system of
      radical generation. Our findings suggest that quercetin protects mouse thymocytes
      from oxidative stress-mediated apoptosis and modulates the intracellular redox
      state through its antioxidant activity.

PMID- 14644161
TI  - Swimming behavior regulation by GABAB receptors in Paramecium.
AB  - In Paramecium, internal Ca(2+) concentration increase coupled to membrane
      depolarization induces a reversal in the direction of ciliary beating and,
      consequently, a reversal in swimming direction. The ciliary reversal (CR)
      duration is correlated to Ca(2+) influx, and the addition of drugs that block the
      Ca(2+) current leads to a reduction in the backward swimming duration. In this
      study we have examined the possible function of GABA(B) receptors in P.
      primaurelia swimming control. The presence of GABA(B) immunoanalogue in
      Paramecium was evidenced using SDS-PAGE, Western blotting, and confocal laser
      scanning microscopy. By applying the specific GABA(B) receptor agonist baclofen,
      a dose-dependent inhibition of the membrane depolarization-induced CR duration
      was observed. This inhibition was antagonized by phaclofen, persisted when K(+)
      channel blockers were applied, and disappeared after treatment with nifedipine
      and verapamil. Moreover, the action of baclofen on depolarization-induced CR was
      suppressed by treatment with pertussis toxin. Therefore, these experiments
      suggest that baclofen modulates CR by a G protein (G(0) or G(1)) mediated
      inhibition of dihydropyridine-sensible calcium channels. Finally, synthesis and
      release of GABA in the environment by Paramecium have been demonstrated by HPLC.
      Possible correlations between GABA(B) receptor activation and the regulation of
      intracellular Ca(2+) levels are discussed.

PMID- 14644162
TI  - The lack of annexin A7 affects functions of primary astrocytes.
AB  - Annexin A7 is a Ca(2+)- and phospholipid-binding protein, which is thought to
      function in membrane organization and Ca(2+)-dependent signaling processes. It
      localizes to different cellular compartments and exists in a 47- and 51-kDa
      isoform with the large isoform being expressed in brain, skeletal, and heart
      muscle. In human temporal brain annexin A7 was found exclusively in astroglial
      cells. As astrocytes are thought to play key roles in several processes of the
      brain we focused on Ca(2+)-dependent signaling processes and astrocyte
      proliferation. Primary astrocytes from an anxA7(-/-) mouse exhibited an increased
      velocity of mechanically induced astrocytic Ca(2+) waves as compared to wild
      type. We also observed a remarkably increased proliferation rate in cultured
      mutant astrocytes. A search for annexin A7 binding partners with advanced
      biochemical methods confirmed sorcin as the major binding protein. However, in
      vivo GFP-tagged annexin A7 and sorcin appeared to redistribute mainly
      independently from each other in wild type and in mutant astrocytes. Our results
      favor an involvement of annexin A7 in Ca(2+)-dependent signaling or Ca(2+)
      homeostasis in astrocytes.

PMID- 14644163
TI  - Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and
      alters cell morphology.
AB  - Cell to cell interaction is one of the key processes effecting angiogenesis and
      endothelial cell function. There are many factors which can mediate this
      interaction including Wnt-signaling-related molecules. Wnt signaling is involved
      in many developmental processes and cellular functions. There is increasing
      evidence suggesting that Wnt signaling has a role in regulating endothelial cell
      growth although the precise mechanism is unclear. In this study, we established a
      coculture system to examine how Wnt-1 signaling regulates human umbilical vein
      endothelial cell (HUVEC) growth and behavior. We found that Wnt-1 signals
      inhibited BrdU incorporation in HUVECs and the number of labeled cells also
      decreased in proportion to the number of Wnt-1-expressing cells present (P <
      0.05). Moreover, HUVECs cocultured with Wnt-1-expressing C57MG cells clumped
      together rather than remaining scattered throughout the culture. These effects
      were dependent on cell contact. Treatment of HUVEC with LiCl, which inhibits the
      activity of GSK-3beta and mimicked Wnt-1 signaling, also inhibited the BrdU
      incorporation in endothelial cells. Our results suggest that Wnt signaling has a
      role in endothelial cell growth control and this is mediated through cell-cell
      contact. They also suggest that Wnt signaling might participate in angiogenesis
      by regulating endothelial cell growth and function.

PMID- 14644164
TI  - The role of c-Src in platelet-derived growth factor alpha receptor
      internalization.
AB  - We used two approaches to investigate the role of Src family kinases (SFKs) in
      ligand-stimulated internalization of the platelet-derived growth factor alpha
      receptor (alphaPDGFR). In cells that normally express SFKs, the internalization
      rate of the F72/74 mutant alphaPDGFR (which is unable to recruit or activate
      SFKs) was slower than that of the wild-type (WT) alphaPDGFR. When expressed in
      cells lacking SFKs (SYF cells), internalization of the WT and mutant receptors
      was indistinguishable, which indicated that there was not an inherent defect in
      the mutant receptor's ability to undergo ligand-driven internalization. The
      internalization difference between the WT and mutant receptors was seen again
      when c-Src was expressed in the SYF cells. Surprisingly, c-Src slowed the
      internalization of the mutant receptor but had little effect on WT receptor. We
      propose the following working hypothesis to explain these findings. In resting
      cells SFKs suppress internalization of the alphaPDGFR by phosphorylating a
      hypothetical protein X. This suppression is relieved when cells are exposed to
      PDGF because SFKs are recruited to the activated WT alphaPDGFR and thereby no
      longer actively phosphorylate protein X. The internalization of the mutant
      receptor is slow because it is unable to recruit SFKs and thereby fails to
      relieve the suppression of internalization. Our findings suggest a role for SFKs
      in regulating the permissiveness for internalization of the alphaPDGFR.

PMID- 14644165
TI  - Myoblast structure affects subsequent skeletal myotube morphology and sarcomere
      assembly.
AB  - Skeletal myogenesis is a precise procedure marked by specific changes in muscle
      cell morphology and cytoarchitecture. Cessation of proliferation by skeletal
      muscle precursor cells (myoblasts) coincides with the induction of fusion to form
      multinucleated myotubes and the initiation of differentiation, the process
      through which sarcomeres are formed. Concurrently, there is a distinct
      upregulation in expression of muscle-specific isoforms and an extreme
      downregulation of non-muscle-specific cytoskeletal isoforms. The sarcomere is the
      contractile unit of the cell and is comprised of a number of different proteins
      aggregated and aligned in very ordered arrays along the myotube. It is this
      rigorously controlled alignment that gives striated muscle its characteristic
      "striped" appearance. Previous studies, conducted predominantly in cardiac
      muscle, propose models for the development of the sarcomere that attribute little
      of the differentiative process to the myoblast morphology and cytoskeletal
      arrangement. In this study, perturbation of myoblast morphology and cytoskeletal
      arrangement by transfection with nonmuscle actin genes in the mouse skeletal
      muscle cell line C2 resulted in myotubes of both varied morphology and sarcomeric
      structure. The results presented herein not only provide novel insights into the
      formation of the sarcomere in skeletal muscle, but also suggest a role for
      myoblast morphology and cytoskeletal structure in the subsequent differentiation
      of the myotube.

PMID- 14644166
TI  - Metal-catalyzed oxidation of extracellular matrix components perturbs hepatocyte
      survival with activation of intracellular signaling pathways.
AB  - To investigate whether oxidative manipulation of extracellular matrix components
      could affect cell survival, we studied primary rat hepatocytes cultured on dishes
      coated with collagen type 1, which was oxidized with a metal-based system.
      Culture of hepatocytes on oxidized collagen led to decreased cellular catalase
      activity along with impaired cell survival. The fraction of polyploid hepatocytes
      decreased early followed by greater reaccumulation of polyploid cells. Cells
      cultured on oxidized collagen showed greater susceptibility to additional oxidant
      stress induced by tert.-butyl-hydroperoxide. The capacity of hepatocytes for
      growth factor-induced DNA synthesis was unaffected by culture on oxidized
      collagen. In response to culture on oxidized matrix, AP-1, Egr-1, CREB, and NF
      kappaB transcription factor activity was rapidly increased. This change in
      transcription factor activity was ameliorated by treatment of collagen with a
      free radical spin trap, N-tert.-butyl-alpha-phenylnitrone, prior to oxidation.
      Moreover, culture of hepatocytes with aminoguanidine, an antioxidant drug,
      decreased cell injury. These findings established that exposure of primary
      hepatocytes to oxidized extracellular matrix components rapidly activates cell
      signaling events with loss of hepatocyte subpopulations. Such cell-extracellular
      matrix interactions may play roles in organ homeostasis and oncogenetic
      progression.

PMID- 14644167
TI  - Integrin alphavbeta3 mediates platelet-derived growth factor-BB-stimulated
      collagen gel contraction in cells expressing signaling deficient integrin
      alpha2beta1.
AB  - The interplay between the collagen-binding integrin, alpha2beta1, and platelet
      derived growth factor (PDGF) receptors in the context of functional interactions
      with collagen was studied. We expressed either wild-type alpha2beta1
      (alpha2beta1A) or alpha2beta1 with a Y783/795F mutation in the cytoplasmic tail
      of the beta1 subunit (alpha2beta1Amut) in the beta1-null fibroblastic cell line,
      GD25. GD25 cells lack endogenous expression of the alpha1 and alpha2 integrin
      subunits and do not adhere to collagen even after transfection with beta1A. Cells
      expressing alpha2beta1Amut contracted three-dimensional collagen lattices less
      efficiently than those expressing alpha2beta1A. PDGF-BB significantly stimulated
      lattice contraction by GD25-alpha2beta1Amut cells. Both cell types responded
      chemotactically to PDGF-BB. Focal adhesion kinase (FAK) and p130(Cas) were
      phosphorylated when GD25-alpha2beta1A cells, but not GD25-alpha2beta1Amut cells
      were seeded on collagen-coated dishes. Subsequent treatment with PDGF-BB further
      increased phosphorylation of FAK and p130(Cas) only in GD25-alpha2beta1A cells.
      However, when cultured within collagen lattices, FAK and p130(Cas)
      phosphorylation were stimulated in both alpha2beta1A- and alpha2beta1Amut
      expressing cells but further phosphorylation, in response to subsequent treatment
      with PDGF-BB, was seen only in GD25-alpha2beta1A cells. We show that the
      stimulatory effects of PDGF-BB on collagen gel contraction and chemotaxis by GD25
      alpha2beta1Amut cells were mediated by the alphavbeta3 integrin. Phosphorylation
      of p130(Cas), but not FAK, in GD25-alpha2beta1Amut cells seeded in collagen
      lattices also depended on alphavbeta3. Our results show that PDGF-BB stimulation
      of fibroblast-collagen interactions is mediated by the alphavbeta3 integrin when
      beta1 integrin function is impaired.

PMID- 14644168
TI  - Thioredoxin inhibits microvascular endothelial capillary tubule formation.
AB  - Thioredoxin (Trx) inhibited human HMEC-1 dermal microvascular endothelial cell
      capillary tubule forming capacity in a Matrigel based assay in vitro. Inhibition
      of capillary tubule formation was Trx catalytic site and thioredoxin reductase
      (TrxR) dependent, mediated at the Matrigel matrix level, and associated with a
      shift from morphological differentiation to continuous proliferation, with
      enhanced cell spreading resulting in eventual monolayer formation. Soluble
      complex carbohydrates, which inhibited capillary tubule formation on Matrigel
      without induction of cell spreading or monolayer formation, failed to impair Trx
      promotion of cell spreading and mono-layer formation, suggesting a shift away
      from carbohydrate-mediated cell/matrix adhesive interactions. Laminin peptides
      YIGRS and SIKVAV, which impaired tubule formation on Matrigel without inducing
      cell spreading or monolayer formation, partially impaired cell spreading upon Trx
      treated Matrigel without restoring tubule formation, consistent with a potential
      role for laminin in Trx-mediated effects. Trx reduced laminin and destabilised
      laminin/galectin-3 complexes within Matrigel. Native purified EHS Laminin (also
      containing galectin-3), but not recombinant galectin-3, restored HMEC-1 capillary
      tubule formation on Trx-treated Matrigel. These data highlight a novel
      deregulatory effect of extracellular Trx upon morphological capillary
      differentiation that appears to depend upon the reduction of laminin and
      destabilisation of its interaction with galectin-3, possibly leading to galectin
      3 neutralisation that shifts cell/matrix adhesive interactions away from being
      carbohydrate mediated and results in loss of proliferation-inhibiting and
      differentiation promoting cues from this tumor basement membrane matrix.

PMID- 14644169
TI  - Analysis of nuclear targeting activities of transport signals in the human
      immunodeficiency virus Rev protein.
AB  - The human immunodeficiency Rev protein shuttles between the nucleus and
      cytoplasm, while accumulating to high levels in the nucleus. Rev has a nuclear
      localization signal (NLS; AA 35-50) with an arginine-rich motif (ARM) that
      interacts with importin beta and a leucine-rich nuclear export signal (NES; AA 75
      84) recognized by CRM1/exportin 1. Here we explore nuclear targeting activities
      of the transport signals of Rev. GFP tagging and quantitative fluorescence
      microscopy were used to study the localization behavior of Rev NLS/ARM mutants
      under conditions inhibiting the export of Rev. Rev mutant M5 was actively
      transported to the nucleus, despite its known failure to bind importin beta.
      Microinjection of transport substrates with Rev-NES peptides revealed that the
      Rev-NES has both nuclear import and export activities. Replacement of amino acid
      residues "PLER" (77-80) of the NES with alanines abolished bidirectional
      transport activity of the Rev-NES. These results indicate that both transport
      signals of Rev have nuclear import capabilities and that the Rev NLS has more
      than one nuclear targeting activity. This suggests that Rev is able to use
      various routes for nuclear entry rather than depending on a single pathway.

PMID- 14644170
TI  - Cholesterol oxides mediated changes in cytoskeletal organisation involves Rho
      GTPases.
AB  - The small GTPases Rho, Rac, and Cdc42 regulate the actin cytoskeleton in all
      eukaryotic cells. In this study we have evaluated the effect of cholesterol
      oxides (7-ketocholesterol and 25-hydroxycholesterol) on cell migration, cell
      adhesion, and cytoskeletal organisation of lens epithelial cells (LEC). Effects
      of cholesterol oxides on cytoskeleton were evaluated by immunofluorescence
      confocal microscopy. The 7-ketocholesterol induced cell arborisation, with
      bundling of vimentin and tubulin in the cell processes and formation of filopodia
      and stress fibres. Cells treated with 25-hydroxycholesterol showed a collapse of
      vimentin filaments towards the nucleus and formation of lamellipodia. In
      addition, cells treated with 7-ketocholesterol or 25-hydroxycholesterol showed
      decreased migration. The effects of cholesterol oxides on cytoskeletal proteins
      involve the activation of the small GTPases Rho, Rac, and Cdc42. Indeed,
      formation of both filopodia and stress fibres induced by 7-ketocholesterol is
      inhibited by overexpressing dominant negatives forms of Cdc42 and RhoA,
      respectively. Similarly, the collapse of vimentin intermediate filament network
      and the formation of lamellipodia, induced by 25-hydroxycholesterol, is inhibited
      by overexpressing dominant negatives forms of Rac1. The effects of cholesterol
      oxides described in this study for LEC are also observed for at least two other
      cell lines (H36CE and U373), suggesting that this may represent a general
      mechanism whereby cholesterol oxides induces cytoskeletal disorganisation.

PMID- 14644173
TI  - Light-harvesting dendrimers.
AB  - Dendrimers are well-defined, tree-like macromolecules, with a high degree of
      order and the possibility to contain selected chemical units in predetermined
      sites of their structure. Dendrimers are currently attracting the interest of
      many scientists because of their unusual chemical and physical properties and the
      wide range of potential applications. It is possible to design and synthesize
      dendrimers containing a variety of chromophoric groups organized in the
      dimensions of time, energy and space so as to obtain efficient light-harvesting
      devices that can be useful for solar energy conversion and other purposes.

PMID- 14644171
TI  - alphaVbeta8 integrin is a Schwann cell receptor for fibrin.
AB  - The interaction of Schwann cells with molecules in the extracellular environment
      following peripheral nerve injury is a critical aspect of nerve repair. A
      principal component of this material is fibrin, which derives from fibrinogen
      infiltrating into the nerve after the injury. This study was undertaken to
      identify cell surface receptor(s) that mediate the interaction of Schwann cells
      with fibrin. We found that adhesion of Schwann cells to fibrin could be
      effectively inhibited by low concentrations of RGD-containing peptides. Among RGD
      sensitive integrins expressed by Schwann cell, alphaVbeta8, but not alpha5beta1,
      was found to bind to fibrin-Sepharose. In contrast, both of these integrins bound
      to fibronectin-Sepharose. We also found that alphaV, but not alpha5 or beta1
      integrin subunit, accumulated in focal contacts of Schwann cell plated on fibrin.
      Taken together, these results strongly suggest that alphaVbeta8 integrin is a
      Schwann cell receptor for fibrin.

PMID- 14644174
TI  - Towards artificial photosynthesis: ruthenium-manganese chemistry mimicking
      photosystem II reactions.
AB  - The reaction center Photosystem II is a key component of the most successful
      solar energy converting machinery on earth: the oxygenic photosynthesis.
      Photosystem II uses light to drive the reduction of plastoquinone and the
      oxidation of water. Water-oxidation is catalyzed by a manganese cluster and gives
      the organism an abundant source of electrons. The principles of photosynthesis
      have inspired chemists to mimic these reactions in artificial molecular
      assemblies. Synthetic light-harvesting antennae and light-induced charge
      separation systems have been demonstrated by several groups. More recently, there
      has been an increasing effort to mimic Photosystem II by coupling light-driven
      charge separation to water oxidation, catalyzed by synthetic manganese complexes.

PMID- 14644175
TI  - Functional models for mononuclear nonheme iron enzymes.
AB  - Increasing interest in mononuclear nonheme iron enzymes that activate dioxygen
      has resulted in an explosion of information on such enzymes in recent years.
      Concomitantly, efforts to model the active sites of these enzymes have produced
      synthetic complexes capable of mimicking some aspect of the reactivity of the
      metal center in several enzymes. These functional models carry out oxidative
      transformations analogous to those catalyzed by the enzymes and in some cases
      allow iron(III)-peroxo or iron(IV)-oxo intermediates to be trapped and
      characterized.

PMID- 14644176
TI  - Imitating the humoral immune response.
AB  - The immune system makes use of two distinct mechanisms to mount an efficient
      response against almost every foreign macromolecular substance. First, antibodies
      with their robust immunoglobulin domain architecture provide a rigid scaffold to
      support six hypervariable loops, capable of forming highly diverse binding sites.
      Second, an efficient genetic mechanism has evolved to create sequence diversity
      at the somatic level in a step-wise process, whereby random recombination of an
      inherited set of gene segments is followed by hypermutation events. Insight into
      the corresponding molecular mechanisms is developing rapidly and enables
      adaptation of the emerging principles to the creation of artificial binding
      proteins in vitro, using the techniques of combinatorial biotechnology. Thus,
      novel types of receptor molecules have been constructed from alternative
      scaffolds, including alpha-helical bundle and beta-barrel proteins. These may
      provide superior tools for the recognition, targeting or separation of a wide
      range of biomolecular structures or substances in biological research,
      technology, and even medicine.

PMID- 14644177
TI  - Evolutionary markers in the (beta/alpha)8-barrel fold.
AB  - Enzymes with the (beta/alpha)(8)-barrel fold are involved in the catalysis of a
      wide variety of biochemical reactions. The active sites of these enzymes are
      located on the C-terminal face of the central beta-barrel. Conserved amino acid
      sequence, as well as secondary, tertiary and quaternary structure patterns are
      providing a rich body of data to support the premise of a common ancestry of many
      members of the (beta/alpha)(8)-barrel fold family of enzymes. Recent data
      indicate that there is at least one example of a bienzyme that functions as an
      ammonia channel, adding a new level of functional diversity to the
      (beta/alpha)(8)-barrel fold. These proteins have become ideal tools that can be
      used in conjunction with directed evolution techniques to engineer novel
      catalytic activities.

PMID- 14644178
TI  - Self-assembly in mesoscopic dimension and artificial supramolecular membranes.
AB  - The development of mesoscopic supramolecular architectures is an area of growing
      interest. The field has grown from early works on bilayer membranes, and the
      design of large (super- or giant-) amphiphiles, hybrid amphiphiles and
      supramolecular membranes have now been described. Impartment of amphiphilicity to
      a unit supermolecule allows their hierarchical self-assembly to the mesoscopic
      structures. A supramolecular combinatorial approach is useful in the development
      of functional self-assemblies. In addition, self-assembly in ionic liquids has
      been introduced as a promising area in materials chemistry.

PMID- 14644179
TI  - Modeling ion channel regulation.
AB  - Remarkable recent successes in structure determinations of voltage-gated
      channels, ligand-gated channels, mechanosensitive channels and proton channels
      have advanced our understanding of the molecular basis of ion channel gating
      substantially. Models have helped to clarify aspects of this process and are now
      being designed as sophisticated biomimetics for various technological
      applications.

PMID- 14644181
TI  - Recent improvements in antigene technology.
AB  - DNA triple-helix-based approaches to control and modulate cellular functions on
      the level of genomic DNA (antigene technology) suffered in the past from a
      stepmother-like treatment in comparison to the flourishing field of
      oligonucleotide-based control of translation (antisense technology). This was
      mostly due to lack of affinity of triplex-forming oligonucleotides to their DNA
      target, to sequence restriction constraints imposed by the triple helical
      recognition motifs and by open questions to the accessibility of the target DNA.
      Recent developments in the area have brought about new bases that specifically
      recognize pyrimidine-purine inversion sites as well as sugar modifications, for
      example, the 2'-aminoethoxy-oligonucleotides or oligonucleotides based on the
      locked nucleic acid sugar unit, which greatly enhance triplex stability and
      alleviate in part the sequence restriction constraints. With this, sequence
      specific genomic DNA manipulation is starting to become a useful tool in
      biotechnology.

PMID- 14644182
TI  - Beyond A, C, G and T: augmenting nature's alphabet.
AB  - Efforts to expand the genetic alphabet are predicated upon a stable and
      replicable third base pair. Recent progress has resulted in the development of
      several candidates that are both stable in duplex DNA and replicated by DNA
      polymerases with various degrees of efficiency and fidelity. The candidate base
      pairs draw upon unnatural hydrogen-bonding topologies as well as upon shape
      complementarity and hydrophobic forces. This review provides a critical
      comparison of the third base pair candidates and discusses the further work
      required to expand the genetic alphabet.

PMID- 14644183
TI  - Synthetic developments towards PNA-peptide conjugates.
AB  - Since the discovery of peptide nucleic acids (PNAs) as DNA mimics in the early
      1990s, a tremendous effort has been directed to their application as antisense
      and antigene probes. With the aim of further enhancing their properties, PNAs
      have been conjugated to a variety of effector molecules. Among these, small
      peptide fragments, often derived from functional proteins, are able to convey
      their specific properties to the conjugate.

PMID- 14644184
TI  - Hydrophilic to amphiphilic design in redox protein maquettes.
AB  - De novo protein design has created small, robust protein-cofactor complexes that
      serve as simplified working models, or maquettes, for the much more complicated
      natural oxidoreductases. We review the research avenues that spring from the
      better characterized water-soluble hydrophilic maquettes and guide the
      construction of amphiphilic maquettes patterned on membrane-bound oxidoreductases
      that couple electron transfer to transmembrane proton-motive force. We address
      the special working challenges and opportunities that arise with amphiphilic
      maquettes designed to assemble in membranes, along with the redox and pigment
      cofactors required to promote light activated electron transfer, redox-coupled
      electric field generation, proton exchange and transmembrane charge motion.

PMID- 14644185
TI  - Synthesis and conformational analysis of arabinofuranosides, galactofuranosides
      and fructofuranosides.
AB  - Many microorganisms produce biologically important polysaccharides containing
      galactofuranosyl, arabinofuranosyl and/or fructofuranosyl residues. Recent
      interest in identifying antibiotics that act by inhibiting the biosynthesis of
      these glycans has resulted in the development of new and efficient methods for
      the assembly of oligosaccharides containing furanose residues. In general, it is
      now possible to synthesize any furanose-containing oligosaccharide with
      reasonable efficiency. In conjunction with these synthetic investigations, an
      increasing number of studies have probed the conformation of furanose rings, and
      a solid appreciation of the conformational preferences of key furanoside ring
      systems is now available.

PMID- 14644186
TI  - Olefin metathesis in glycobiology: new routes towards diverse neoglycoconjugates.
AB  - This report provides a historical overview of the implementation of olefin
      metathesis in carbohydrate chemistry, with the emphasis on the construction of
      neoglycoconjugates. The current state-of-the-art in catalyst design allows the
      preparation of carbohydrate-containing molecules with great structural and
      functional diversity. Recent examples of complex neoglycoconjugates, including
      glycopolymers, glycoclusters, glycopeptide and glycolipid analogues are
      highlighted. Finally, future perspectives in the scope of olefin metathesis
      mediated neoglycoconjugate synthesis are discussed.

PMID- 14644187
TI  - Cell division, growth and death. Cell growth: live and let die.

PMID- 14644188
TI  - The morphogenesis checkpoint: how yeast cells watch their figures.
AB  - The morphogenesis checkpoint maintains coordination between the process of bud
      formation and the nuclear events of the cell cycle in yeast. This checkpoint
      regulates the Wee1 homolog, Swe1p, to induce cell-cycle delay or arrest when
      aspects of bud formation are defective. A variety of studies have suggested that
      this checkpoint can monitor actin organization, septin organization, the presence
      of a bud and even the size of a bud. The evidence for these proposals is
      reviewed, highlighting recent findings indicating that Swe1p degradation is
      controlled by the cell shape change that accompanies bud emergence.

PMID- 14644189
TI  - Cell-cycle control during meiotic maturation.
AB  - The meiotic cell cycle, which is comprised of two consecutive M-phases, is
      crucial for the production of haploid germ cells. Although both mitotic and
      meiotic M-phases share cyclin-B-Cdc2/CDK1 as a key controller, there are meiosis
      specific modulations in the regulation of cyclin-B-Cdc2. Recent insights indicate
      that a common pattern in these modulations can be found by considering the
      particular activities of mitogen-activated protein kinase (MAPK) during meiosis.
      The G(2)-phase arrest of meiosis I is released via specific, MAPK-independent
      signalling that leads to cyclin-B-Cdc2 activation; thereafter, however, the
      meiotic process is under the control of interplay between MAPK and cyclin-B-Cdc2.

PMID- 14644190
TI  - Dynamics of chromosome positioning during the cell cycle.
AB  - The arrangement and dynamics of chromosomes inside the nucleus of mammalian cells
      have been studied intensively over the last two years. Although chromosomes are
      relatively immobile and occupy non-random positions in interphase, their dynamic
      movements in mitosis have traditionally been assumed to randomize this
      arrangement. New methods of live cell imaging now make it possible to follow
      chromosome movements directly and quantitatively in single cells. Such studies
      have generated models of chromosome positioning throughout the cell cycle and
      provide a new basis to address the underlying mechanisms in future experiments.

PMID- 14644191
TI  - Mitotic mechanics: the auroras come into view.
AB  - Aurora kinases have recently taken centre stage in the regulation of key cell
      cycle processes. Aurora A is emerging as a critical regulator of centrosome and
      spindle function. Aurora B mediates chromosome segregation by ensuring proper
      biorientation of sister chromatids, possibly through the regulation of
      microtubule dynamics. This enzyme also functions in cytokinesis apparently by
      interacting with a critical GTPase and a kinesin-like protein. Recent work on
      both kinases has revealed functional links between Aurora kinase activity and the
      mechanics of cell division.

PMID- 14644192
TI  - Cytokinesis: progress on all fronts.
AB  - Cell multiplication requires sequestration of the duplicated and segregated
      genome into two daughter cells. The mitotic spindle is critical for orchestrating
      sister chromatid separation and division plane positioning. During anaphase,
      spindle microtubules become bundled to form the central spindle, which is
      essential for completion of cytokinesis. Central spindle assembly is mediated by
      a microtubule-associated protein and a kinesin-RhoGAP complex, both of which are
      regulated by phosphorylation/dephosphorylation. The central spindle also plays a
      role in cleavage furrow positioning, which appears to involve activation of RhoA.
      New results have provided some initial clues as to how furrow positioning is
      achieved. Particularly notable is the discovery that a protein activated by RhoA,
      formin, has actin nucleation activity.

PMID- 14644193
TI  - Bcl-2-family proteins and the role of mitochondria in apoptosis.
AB  - Mitochondria are central to many forms of cell death, usually via the release of
      pro-apoptotic proteins from the mitochondrial intermembrane space. Some
      intermembrane space proteins, including cytochrome c, Smac/DIABLO, and Omi/Htra2,
      can induce or enhance caspase activation, whereas others, such as AIF and
      endonuclease G, might act in a caspase-independent manner. Intermembrane space
      protein release is often regulated by Bcl-2-family proteins. Recent evidence
      suggests that pro-apoptotic members of this family, by themselves, can
      permeabilize the outer mitochondrial membrane without otherwise damaging
      mitochondria. Mitochondria can contribute to cell death in other ways. For
      example, they can respond to calcium release from the endoplasmic reticulum by
      undergoing the mitochondrial permeability transition, which in turn causes outer
      membrane rupture and the release of intermembrane space proteins. Bcl-2-family
      proteins can influence the levels of releasable Ca(2+) in the endoplasmic
      reticulum, and thus determine whether the released Ca(2+) is sufficient to
      overload mitochondria and induce cell death.

PMID- 14644194
TI  - Viral modulators of cell death provide new links to old pathways.
AB  - By observing how viruses facilitate their parasitic relationships with host
      cells, we gain insights into key regulatory pathways of the cell. Not only are
      mitochondria key players in the regulation of programmed cell death, but many
      viral regulators of cell death also alter mitochondrial functions either directly
      or indirectly. Although cytomegalovirus vMIA and Epstein-Barr virus BHRF1 seem to
      have opposite effects on mitochondrial morphology, they both inhibit cell death.
      Drosophila Reaper, a regulator of developmental cell death, acts on IAP
      (inhibitor of apoptosis) proteins to activate caspases, but can regulate
      mitochondrial permeability in vitro. Despite its pivotal role in Drosophila,
      homologues of Reaper in other species were not previously known. Recently, amino
      acid sequence similarity was recognized between Drosophila Reaper and a protein
      known to be important for the replication and virulence of mosquito-borne
      bunyaviruses that cause human encephalitis. Thus, viral mechanisms for regulating
      apoptosis are diverse and not fully elucidated but promise to provide new
      insights.

PMID- 14644195
TI  - Mitochondrial fission in apoptosis, neurodegeneration and aging.
AB  - A decline in mitochondrial function is well recognized in neurodegenerative
      diseases and aging, and is thought to play a causal role in their biology.
      Unfortunately, the molecular basis underlying this detrimental loss in
      mitochondrial function remains mysterious. Interestingly, mitochondria undergo
      frequent fission and fusion. This process is regulated by molecular machinery
      that has been highly conserved during evolution, including dynamin-related
      GTPases that manifest opposing effects. A balance between mitochondrial fission
      and fusion events is required for normal mitochondrial and cellular function.
      Emerging evidence indicates that mitochondria undergo rapid and extensive fission
      at an early stage during apoptosis. A clue that these new findings are of
      significance for the pathogenesis of neurodegenerative disease is provided by the
      observation that OPA-1, a dynamin-related GTPase regulating mitochondrial fusion,
      is mutated in humans with dominant optic atrophy, which is characterized by
      degeneration of retinal ganglion cells and childhood blindness. Loss of function
      of OPA-1, analogous to deficiency of its yeast homologue, Mgm1p, is expected to
      lead to mitochondrial fission, loss of mitochondrial DNA, respiratory deficits
      and an increase in reactive oxygen species. Here we review the molecular
      mediators controlling mitochondrial fission and fusion, and how death effector
      molecules may hijack this ancient machinery. A shift in the rate of mitochondrial
      fission or fusion may provide a new mechanistic explanation for the mitochondrial
      dysfunction in neurodegenerative diseases and normal aging, and may offer a new
      target for therapeutic intervention.

PMID- 14644196
TI  - Regulators of IAP function: coming to grips with the grim reaper.
AB  - Inhibitor of apoptosis proteins (IAPs) are a conserved class of proteins that
      control apoptosis in both vertebrates and invertebrates. They exert their anti
      apoptotic function through inhibition of caspases, the principal executioners of
      apoptotic cell death. Recent advances in vertebrates and Drosophila have
      demonstrated that IAPs use ubiquitin conjugation to control the stability, and
      thus the activity, of select target proteins. The Drosophila IAP1 gene is an
      instructive example: it employs at least two distinct ubiquitin-dependent
      mechanisms of protein destruction. The apoptosis-inducing genes grim, reaper and
      hid modulate these mechanisms, and determine the outcome.

PMID- 14644197
TI  - Mechanisms of caspase activation.
AB  - The core effectors of apoptosis encompass proteolytic enzymes of the caspase
      family, which reside as latent precursors in most nucleated metazoan cells. A
      majority of studies on apoptosis are based on the assumption that caspase
      precursors are activated by cleavage, a common mechanism for most protease
      zymogen activations. Although this appears to be true for the executioner
      caspases, recent research points to a distinct activation mechanism for the
      initiator caspases that trigger the apoptotic pathways. This mechanism is
      proximity-induced dimerization without cleavage, and its elucidation has led to
      the revision of concepts of feedback regulation of apoptosis.

PMID- 14644198
TI  - Dying for NF-kappaB? Control of cell death by transcriptional regulation of the
      apoptotic machinery.
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) is a pleiotropic
      protein complex that is activated from a sequestered, cytoplasmic form by pro
      inflammatory extracellular signals and cellular stress. Several hundred cellular
      genes have been shown to be regulated by NF-kappaB, including cytokines,
      chemokines and adhesion molecules. Nearly eight years ago, a flurry of
      publications showed that loss or suppression of NF-kappaB results in an enhanced
      sensitivity to apoptosis. In the ensuing years, activation of NF-kappaB has
      become almost synonymous with enhanced cell survival, although more recent data
      suggests that this transcription factor plays a more complex role in the
      regulation of cell death.

PMID- 14644200
TI  - Epithelial-mesenchymal transitions in development and pathologies.
AB  - The epithelial-mesenchymal transition (EMT) is a fundamental process governing
      morphogenesis in multicellular organisms. This process is also reactivated in a
      variety of diseases including fibrosis and in the progression of carcinoma. The
      molecular mechanisms of EMT were primarily studied in epithelial cell lines,
      leading to the discovery of transduction pathways involved in the loss of
      epithelial cell polarity and the acquisition of a variety of mesenchymal
      phenotypic traits. Similar mechanisms have also been uncovered in vivo in
      different species, showing that EMT is controlled by remarkably well-conserved
      mechanisms. Current studies further emphasise the critical importance of EMT and
      provide a better molecular and functional definition of mesenchymal cells and how
      they emerged >500 million years ago as a key event in evolution.

PMID- 14644201
TI  - Apicobasal polarization: epithelial form and function.
AB  - The structure and function of epithelial sheets generally depend on apicobasal
      polarization, which is achieved and maintained by linking asymmetrically
      distributed intercellular junctions to the cytoskeleton of individual cells.
      Recent studies in both Drosophila and vertebrate epithelia have yielded new
      insights into the conserved mechanisms by which apicobasal polarity is
      established and maintained during development. In mature polarized epithelia,
      apicobasal polarity is important for the establishment of adhesive junctions and
      the formation of a paracellular diffusion barrier that prevents the movement of
      solutes across the epithelium. Recent findings show that segregation of ligand
      and receptor with one on each side of this barrier can be a crucial regulator of
      cell-cell signaling events.

PMID- 14644202
TI  - Tissue architecture: the ultimate regulator of breast epithelial function.

PMID- 14644203
TI  - Live and let die in the intestinal epithelium.
AB  - The intestinal epithelium is a relatively simple developmental system and a prime
      example of tissue renewal from a source of multipotent stem cells. Throughout
      adulthood, intestinal epithelial proliferation, cell-fate specification and
      differentiation are coupled to migration in discrete units known as crypts of
      Lieberkuhn. Physically guided by Eph receptors and their ligands, the ephrins,
      stem cell progeny transit through the proliferation/differentiation switch, and
      Notch diversifies their subsequent fates. Wnt signalling appears to control most
      of these events.

PMID- 14644204
TI  - The multifaceted adult epidermal stem cell.
AB  - Adult epidermal stem cells renew the epithelial compartment of the skin
      throughout life and are the most accessible of all adult stem cells. Most
      importantly, epidermal stem cells can be efficiently cultivated and transplanted,
      a significant advantage for cell and gene therapy. Recent work has pointed to the
      hair follicle as the main repository of multipotent stem cells in skin. Hair
      follicles, which are often affected in the mouse by spontaneous or man-made
      mutations, have become superb model systems to study the cellular and molecular
      factors that regulate the proliferation, migration and fate of adult stem cells.

PMID- 14644205
TI  - Complex redundancy to build a simple epidermal permeability barrier.
AB  - To survive the transition from an aqueous in utero to a terrestrial ex utero
      environment, mice and humans must construct an epidermal permeability barrier in
      utero. Terminally differentiated epidermal cells, lipids and tight junctions are
      all essential to achieve this barrier. Recent analyses of mouse mutants with
      defects in structural components of the terminally differentiated epidermal cell,
      catalyzing enzymes, lipid processing, transcriptional regulators and the
      intercellular junctions have highlighted their essential function in establishing
      the epidermal permeability barrier. Particularly interesting examples include
      modulation of the expression of transglutaminase 1 enzyme, the transcription
      factor Klf4 and the claudin tight junction proteins. However, careful analysis of
      the various mutant phenotypes during embryonic development, as neonates and
      either as adults or transplanted skin, has revealed much more about the
      redundancy and compensatory mechanisms of the system. Molecular analysis of the
      various mouse mutants has demonstrated common pathways to compensate for loss of
      the epidermal barrier.

PMID- 14644206
TI  - Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of
      disease.
AB  - PURPOSE: To update clinical information about ocular toxoplasmosis. Part I
      reviews information about prevalence of disease, sources of infection, relation
      of ocular disease to time of Toxoplasma gondii infection (congenital vs.
      postnatally acquired), and course of disease. DESIGN: Literature review. METHODS:
      Selected articles from the medical literature, information from recent scientific
      meetings, and the author's personal experiences were reviewed critically in
      preparation for the LX Edward Jackson Memorial Lecture. RESULTS: The prevalence
      of T. gondii infection varies geographically and increases with age; in the
      United States, the overall proportion is 22.5%. The proportion of infected
      individuals in the United States who have had episodes of ocular toxoplasmosis is
      unknown, but may be approximately 2%. Prevalence of ocular involvement is
      substantially greater in other parts of the world, including southern Brazil. In
      addition to undercooked meat and unwashed vegetables, drinking water contaminated
      with oocysts may be an important source of infection in some settings. In
      contrast to traditional teaching, evidence suggests that most individuals with
      ocular toxoplasmosis were infected postnatally. Ocular lesions may first develop
      many years after T. gondii infection. The risk of recurrent ocular disease
      appears to be greater during the first year after an episode of toxoplasmic
      retinochoroiditis than during subsequent years. CONCLUSIONS: Reassessment of
      older publications in the light of recent observations provides a richer
      understanding of ocular toxoplasmosis, although knowledge about the disease
      remains incomplete. A better understanding of the clinical characteristics and
      course of ocular toxoplasmosis will have important implications for developing
      more effective prevention and treatment strategies.

PMID- 14644207
TI  - Management of post-vitrectomy persistent vitreous hemorrhage in pseudophakic
      eyes.
AB  - PURPOSE: To prospectively assess the effect of neodymium:yttrium-aluminum-garnet
      peripheral capsulotomy on postvitrectomy hemorrhage in diabetic patients with a
      posterior chamber intraocular lens (IOL) implant and an intact posterior capsule.
      DESIGN: Interventional case series. METHODS: This is a prospective case series,
      clinical practice. PATIENTS: Five vitrectomized, diabetic, pseudophakic patients
      with persistent vitreous cavity hemorrhage remaining after vitrectomy were
      selected. They all had a posterior chamber IOL implant with an intact posterior
      capsule. Additionally, they had all undergone laser panretinal photocoagulation
      in the involved eye in the past for diabetic retinopathy. Neodymium:yttrium
      aluminum-garnet laser capsulotomy outside the optic of the IOL was performed in
      victrectomized diabetic patients to treat the remaining vitreous cavity
      hemorrhage. Visual acuity, intraocular pressure (IOP), and fundus examination
      were measured and done immediately after the laser procedure, in 7 days and in
      approximately 3 months. RESULTS: The visual acuity was improved at the time of
      the first follow-up. However, a mild elevation of IOP was noticed in some
      patients, which was treated with topical dorzolamide. The final visual acuity was
      dramatically improved, to 20/30 or better, and the IOP was normalized without
      medication within a few weeks in all five cases. No neovascularization of the
      iris or elsewhere was noticed in any case. CONCLUSIONS: Neodymium:yttrium
      aluminum-garnet laser peripheral capsulotomy appears to be a safe and effective
      management procedure in treating postvitrectomy hemorrhage in diabetic patients
      who have previously undergone cataract surgery with posterior chamber lens
      implant, intact posterior capsule, and extensive panretinal photocoagulation. The
      vitreous hemorrhage cleared completely in all five cases.

PMID- 14644208
TI  - Aqueous shunt devices compared with trabeculectomy with Mitomycin-C for children
      in the first two years of life.
AB  - PURPOSE: To compare the outcomes of children 24 months of age or younger treated
      with aqueous shunt devices or with mitomycin-C (MMC) trabeculectomy. DESIGN:
      Retrospective, age-matched, comparative case series. METHODS: Forty-six eyes of
      32 patients with mean age of 7.0 +/- 5.1 month (range, 1 to 22 months) and
      uncontrolled glaucoma, which received an aqueous shunt device (Ahmed glaucoma
      valve or Baerveldt implant), compared with 24 eyes of 19 patients with mean age
      of 5.3 +/- 4.8 months (range, 0.5 to 24 months), which received an MMC
      trabeculectomy. Surgical success was defined as intraocular pressure < 23 mm Hg
      on maximal glaucoma medication, no further glaucoma surgery performed or
      recommended, no devastating complication, and stable ocular dimensions (axial
      length and corneal diameter). RESULTS: Cumulative probabilities of success were
      87% +/- 5.0% for the aqueous shunt group compared with 36% +/- 8.0% success in
      the trabeculectomy group at 12 months and 53% +/- 12% in the aqueous shunt group
      compared with 19% +/- 7% in the trabeculectomy group at 72 months (chi(2) of
      23.5, P <.0001). Aqueous shunt implantation was associated with significantly
      more postoperative complications requiring a return to the operating room (21 of
      46 eyes, 45.7%) compared with trabeculectomy with MMC (3 of 24 eyes, 12.5%, P
      =.0074). The most common postoperative procedure in the aqueous shunt group was
      tube repositioning, performed in 16 of 46 eyes (34.8%). CONCLUSIONS: Aqueous
      shunt implantation offers a significantly greater chance of successful glaucoma
      control in the first 2 years of life, compared with trabeculectomy with MMC.
      However, the enhanced success with aqueous shunt devices is associated with a
      higher likelihood of postoperative complications requiring surgical revision,
      most commonly tube repositioning.

PMID- 14644209
TI  - Evaluation of the hypertensive phase after insertion of the Ahmed Glaucoma Valve.
AB  - PURPOSE: To investigate the postoperative hypertensive phase (HP) in patients
      undergoing glaucoma drainage implant surgery. DESIGN: Interventional case series.
      METHODS: A retrospective chart review of 156 consecutive eyes (139 patients) who
      underwent placement of an Ahmed Glaucoma Valve (AGV) with a follow-up of >or=3
      months was performed. Main outcome measures were occurrence and resolution of the
      HP and intraocular pressure (IOP) control. The HP was defined as IOP > 21 mm Hg
      during the first 3 months after surgery. Resolution of the HP was defined as an
      IOP < 22 mm Hg and an IOP reduction of 3 mm Hg with the same or fewer number of
      glaucoma medications. RESULTS: An HP was observed in 88 eyes (56%). It occurred
      after a mean of 5.0 weeks (median, 4 weeks; range, 1-13 weeks) with an average
      (+/- standard deviation) peak IOP of 30.1 (+/- 7.5) mm Hg. Resolution of the HP
      occurred in 19 of 68 eyes (28%) with available data. Eyes with an HP had a higher
      mean IOP and needed more medications 6 to 12 months after surgery than eyes
      without an HP (17.2 +/- 5.6 vs 14.3 +/- 5.8 mm Hg; P =.012 and 1.7 +/- 1.2 vs 0.3
      +/- 0.6 medications; P <.001, respectively). CONCLUSION: A hypertensive phase
      occurs frequently after implantation of the AGV. However, it resolves in only a
      minority of eyes. The majority of eyes with an HP have no significant improvement
      of IOP control and continue to require the same number of glaucoma medications as
      they did during the HP.

PMID- 14644210
TI  - Incidence and management of cataract after retinal detachment repair with
      silicone oil in immune compromised patients with cytomegalovirus retinitis.
AB  - PURPOSE: To determine the incidence of and risk factors for cataract and to
      describe the visual outcomes of cataract surgery in eyes with cytomegalovirus
      related retinal detachments repaired with silicone oil. STUDY DESIGN:
      Retrospective cohort study. METHODS: A prospectively generated database of all
      patients with cytomegalovirus retinitis examined at a single tertiary care
      institution was used to identify all cases of retinal detachment between October
      1983 and August 1997. Data on retinal detachment repair, development of cataract,
      and outcomes of cataract surgery were obtained retrospectively. RESULTS: Among
      904 eyes of 587 immune-compromised patients diagnosed with cytomegalovirus
      retinitis, 198 eyes of 155 patients developed retinal detachment. Among these,
      106 eyes of 90 patients underwent retinal detachment repair with silicone oil.
      The Kaplan-Meier estimated median time to cataract was 1.8 months after surgery
      with silicone oil. The adjusted relative risk of cataract in eyes that underwent
      retinal detachment repair with silicone oil compared with eyes that did not was
      6.74 (P <.0001). Eight of the eyes that developed cataract underwent
      uncomplicated cataract surgery by phacoemulsification and posterior chamber
      intraocular lens implantation. Among these, six eyes experienced >or=2 lines of
      improvement in visual acuity. All developed posterior capsule opacification a
      median of 7 days after cataract surgery. Four of five eyes that that underwent
      neodymium:yttrium-aluminum-garnet laser capsulotomy experienced >or=2 lines
      improvement in visual acuity. CONCLUSIONS: There is a high incidence of cataract
      after surgery with silicone oil tamponade for cytomegalovirus-related retinal
      detachment. Posterior capsule opacification occurs rapidly after cataract surgery
      in these patients.

PMID- 14644211
TI  - Influence of cataract surgery with implantation of different intraocular lenses
      on scanning laser tomography and polarimetry.
AB  - PURPOSE: To describe the influence of cataract surgery with implantation of
      different intraocular lenses on scanning laser tomography (SLT) and scanning
      laser polarimetry (SLP) and to measure the birefringent properties of intraocular
      lenses in a laboratory setting. DESIGN: Prospective cohort study. METHODS: The
      influence of phacoemulsification cataract surgery with intraocular lens
      implantation (56 polymethylmethacrylate [PMMA; 31 Pharmacia/Upjohn 811 B and 25
      Domilens Flex 60]; 25 hydroxyethylmethacrylate/methylmethacrylate (HEMA/MMA)
      [Technomed, Memory Lens]; 32 silicone [Allergan Si40]; 25 acrylic [Storz
      Hydroview]) on SLP and SLT measurements was evaluated preoperatively and 3 to 4
      weeks postoperatively in 138 eyes of otherwise healthy patients. Lens opacities
      were classified according to the Lens Opacities Classification System III (LOCS
      III). Imaging was performed with TopSS and GDx (Laser Diagnostic Technologies,
      San Diego, California, USA) for SLT and SLP, respectively. Additionally,
      birefringent properties of intraocular lenses were measured in a laboratory
      setting. RESULTS: Our results show that imaging with SLT and SLP is possible with
      lens opacity-induced visual acuity reductions down to 0.2 and 0.16, respectively.
      There were no significant differences in the topographic parameters assessed
      before and after cataract surgery with SLT. However, standard deviations between
      three within-session single measurements were smaller postoperatively. Nerve
      fiber layer patterns were similar before and after cataract surgery with SLP,
      whereas certain total nerve fiber layer thickness values were significantly
      higher postoperatively. As a consequence, "the number" is significantly lower in
      the Domilens Flex 60 group (P =.01) and in the Storz Hydroview group (P =.02),
      and with a tendency also in the other groups as well. Measurements with a high
      resolution optical bench revealed no birefringent properties of the implanted
      lenses. CONCLUSIONS: Our results indicate that after cataract surgery with
      intraocular lens implantation some SLP values are altered significantly, whereas
      SLT parameters are not influenced. These findings are of clinical interest,
      especially in the follow-up of glaucoma patients.

PMID- 14644212
TI  - Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma
      patients, ocular hypertensives, and normal subjects.
AB  - PURPOSE: To compare optic nerve head (ONH) and peripapillary retinal blood flow
      in subjects with open-angle glaucoma (OAG), ocular hypertension (OHT), and normal
      eyes (NOR) using full-field perfusion analysis of scanning laser Doppler
      flowmetry (SLDF) images. DESIGN: Prospective, nonrandomized clinical trial.
      METHODS: Twenty uncontrolled OAG patients, 20 uncontrolled OHT patients, and 20
      normal volunteers were prospectively enrolled. Mean ONH and peripapillary retinal
      blood flow measurements were performed by SLDF version 3.3 using five Heidelberg
      Retina Flowmeter (Heidelberg Engineering, Heidelberg, Germany) images.
      Statistical evaluations were performed on the three study groups using one-way
      analysis of variance. Flow values of the neuroretinal rim of the ONH, nasal
      peripapillary retina, and temporal peripapillary retina were then correlated with
      the clinical parameters of age, cup/disk (C/D) ratio, intraocular pressure (IOP),
      visual field mean defect, maximum-recorded IOP, and ocular perfusion pressure.
      Neuroretinal rim blood flow in the OAG group was 158 +/- 79 arbitrary units (au),
      whereas in the OHT group it was 277 +/- 158 au, and in the NOR group it was 272
      +/- 93 au. Differences were statistically significant between the OAG group and
      each of the other groups (P =.001) but not between OHT and NOR groups (P =.91).
      Peripapillary retinal flow values showed no statistically significant differences
      between groups (P =.76 nasal and 0.93 temporal). RESULTS: Neuroretinal rim flow
      values showed a significant inverse correlation with C/D ratio (P =.001). Mean
      neuroretinal rim blood flow was significantly higher (350 +/- 184 au) in the 10
      OHT patients with C/D ratios < 0.4 when compared with the 10 OHT patients with
      larger C/D ratios (203 +/- 79 au) (P =.039). Conversely, peripapillary retinal
      blood flow showed no significant correlation with any clinical parameter.
      CONCLUSION: Open-angle glaucoma patients had significantly lower blood flow in
      the ONH compared with OHT patients and normal volunteers. No significant
      differences in ONH blood flow were found between ocular hypertensives and normal
      volunteers. For peripapillary retinal blood flow, no significant difference was
      seen between any groups. Neuroretinal rim blood flow was significantly inversely
      correlated to increased C/D ratio. Ocular hypertensives with larger C/D ratios
      demonstrated significantly lower rim blood flow compared with those with smaller
      C/D ratios, suggesting that rim perfusion might be reduced in high-risk ocular
      hypertensives before the manifestation of visual field defects.

PMID- 14644213
TI  - Corneal ciprofloxacin precipitation during bacterial keratitis.
AB  - PURPOSE: To examine how age affects the risk of developing a white corneal
      precipitate during ciprofloxacin therapy for bacterial keratitis and to explore
      the effect of a white precipitate on rates of clinical improvement and cure.
      DESIGN: Prospective, multicenter, observational cohort study. METHODS: Occurrence
      of a white precipitate of the corneal surface was recorded among 624 patients
      with presumed bacterial keratitis who were treated with topical ciprofloxacin
      0.3% solution or ointment. Relative risks of corneal precipitation were estimated
      from logistic regression for age categories and other clinical characteristics.
      The time-dependent effects of precipitate on rates of infection resolution and
      corneal reepithelialization were estimated by proportional hazards regression.
      RESULTS: Ninety-five (15.2%) patients developed a white corneal precipitate
      during ciprofloxacin therapy; 72 (75.8%) began within the first 3 days of
      treatment. Compared with those younger than 40 years old, patients aged 60 to 69
      years had 2.8 (95% confidence limits [CL], 1.9, 3.9) times the risk of
      ciprofloxacin precipitation; patients 70 years and older had 3.7 (95% CL, 2.6,
      5.0) times the risk. Median duration of the visible corneal precipitate was 8.5
      days (90% decile, 32 days). Presence of ciprofloxacin precipitation did not
      significantly affect the time until therapeutic improvement (P =.09) but slowed
      the time until reepithelialization by 55% (95% CL 32%, 70%). CONCLUSIONS: Older
      patients treated with topical ciprofloxacin for bacterial keratitis have a higher
      risk of corneal deposition. A white precipitate apparently does not interfere
      with antibacterial therapeutic response but may delay epithelial healing of
      ulcerative keratitis.

PMID- 14644214
TI  - Short posterior ciliary artery, central retinal artery, and choroidal
      hemodynamics in brimonidine-treated primary open-angle glaucoma patients.
AB  - PURPOSE: Malfunction in peripapillary hemodynamics has been suggested to play a
      major part in the pathogenesis of primary open-angle glaucoma (POAG). The aim of
      this study was to determine whether topically applied brimonidine can influence
      blood hemodynamic characteristics associated with the perioptic short posterior
      ciliary arteries (SPCAs), central retinal artery (CRA), and choroidal vascular
      system in POAG patients. DESIGN: Randomized clinical trial. In this prospective,
      institutional, double-masked, vehicle-controlled, randomized clinical trial, the
      intraocular pressure (IOP) and vascular dynamics of the SPCAs, CRA, and choroidal
      vascular system were analyzed in both eyes of 17 POAG patients, before and after
      treatment with 0.2% brimonidine for 4 weeks. RESULTS: Mean IOP reduction was
      significant (18.7%) following treatment with brimonidine. However, no clear
      changes were recorded with respect to blood perfusion parameters (peak systolic
      velocity, end-diastolic velocity, pulsatility, and resistance indices) associated
      with the SPCAs and CRA or the choroidal ocular pulse amplitude. CONCLUSIONS:
      Topical treatment of brimonidine to POAG patients causes a significant reduction
      of IOP, but blood hemodynamic properties associated with the SPCAs, CRA, and
      choroidal vascular systems appeared unaffected. Topically applied brimonidine,
      therefore, appears not to constrict or dilate peripapillary blood vessels.

PMID- 14644215
TI  - Japanese age-related macular degeneration trial: 1-year results of photodynamic
      therapy with verteporfin in Japanese patients with subfoveal choroidal
      neovascularization secondary to age-related macular degeneration.
AB  - PURPOSE: To determine the effect and safety of verteporfin therapy (Visudyne) in
      Japanese age-related macular degeneration (AMD) patients. DESIGN: Open-label,
      multicenter, prospective, noncontrolled study. METHODS: The setting was five
      university hospitals in Japan. The study population was patients at least 50
      years old, with best-corrected visual acuity of 20/40 to 20/200 inclusive and
      fluorescein angiography documenting subfoveal, classic-containing choroidal
      neovascularization (CNV) secondary to AMD and a lesion of greatest linear
      dimension <or= 5400 microm. For the intervention, patients received verteporfin
      intravenously followed by light administration 15 minutes after the infusion
      start. Additional treatment was given every 3 months through month 9 if leakage
      from CNV was observed on angiogram. The main outcome measure was percentage of
      lesions with progression of classic CNV beyond the area of the baseline lesion.
      RESULTS: Sixty-four patients were enrolled at five centers, and 61 patients
      completed the study. The median number of treatments given during the trial was
      three. At the 12-month examination, 12 patients (19%; 95% confidence interval:
      11%-31%) had progression of classic CNV whereas 32 (50%) and 49 (77%) patients
      had no leakage from classic or occult CNV, respectively. The median visual acuity
      score (approximate Snellen equivalent) from baseline to month 12 increased from
      50.0 (20/100)-56.5 (20/80(+2)) letters. Fourteen patients (22%) had visual
      disturbances, including two patients (3%) with acute vision decrease considered
      as serious adverse events and one patient (2%) with infusion-related back pain.
      No photosensitivity reactions were reported. CONCLUSIONS: Verteporfin therapy for
      subfoveal CNV in these Japanese patients appeared to have a similar or better
      angiographic and vision effect as that observed in Caucasian patients, with the
      same safety profile, supporting its use in Japanese patients.

PMID- 14644216
TI  - Reduced need for corneal epithelial debridement during vitreo-retinal surgery
      using two different viscous surface lubricants.
AB  - PURPOSE: Corneal clarity is frequently reduced during vitrectomy and scleral
      buckling surgery secondary to epithelial edema, requiring epithelial debridement
      to improve visibility. The presence of toxic preservatives in the corneal
      lubricant solutions is hypothesized to be a contributing factor to epithelial
      edema during vitreo-retinal surgery. DESIGN: Interventional study. METHODS: We
      compared prospectively the corneal clarity and epithelial debridement frequency
      in 71 patients within a single institution in whom either Goniosol (2.5%
      methylcellulose, boric acid, edetate disodium, sodium borate, potassium chloride,
      water, and 0.01% benzalkonium chloride) or GenTeal gel (0.3% hydoxypropyl
      methylcellulose, carbopol 980, phosphonic acid, sorbitol, water, and 0.028%
      sodium perborate) was used as a corneal lubricant during the course of vitrectomy
      surgery using sutured contact lenses. Corneal clarity was subjectively graded in
      a scale of I to IV during surgery. Statistical analysis was made between these
      two groups for parametric and categorical data. RESULTS: All eyes started with a
      corneal clarity grade of I (best possible). Corneal clarity decreased
      significantly faster in eyes where Goniosol was used to a median grade of III at
      1 hour of surgical time. In eyes where GenTeal gel was used, corneal clarity
      decreased much slower, to a median grade of I at 1 hour of surgical time. The
      difference in frequency of epithelial debridement was also statistically
      significant: 54% and 14% for Goniosol and GenTeal eyes, respectively. Other
      factors that may cause corneal epithelial edema and affect corneal clarity were
      not statistically different between the Goniosol and the GenTeal groups,
      including median operative time, estimated intraocular pressure, pre- and
      intraoperative topical solutions and medications, and number of prior ocular
      procedures. CONCLUSIONS: The use of GenTeal gel as a corneal lubricant maintains
      corneal clarity longer than Goniosol during the course of vitrectomy surgery
      using a contact lens viewing system, limiting the need for epithelial
      debridement.

PMID- 14644217
TI  - Characteristics of visual loss by scanning laser ophthalmoscope microperimetry in
      eyes with subfoveal choroidal neovascularization secondary to age-related macular
      degeneration.
AB  - PURPOSE: To evaluate the effects of subfoveal choroidal neovascularization
      secondary to age-related macular degeneration on functional parameters obtained
      by scanning laser ophthalmoscope microperimetry. DESIGN: Retrospective
      observational case series and cross-sectional study. METHODS: At the Doheny
      Retina Institute and Wilmer Eye Institute a consecutive series of 179 eyes of 175
      patients with subfoveal choroidal neovascularization secondary to age-related
      macular degeneration was studied. The onset of visual symptoms, best-corrected
      visual acuity, fluorescein angiography, evaluation of fundus microperimetry and
      fixation pattern using the Rodenstock scanning laser ophthalmoscope were obtained
      for each patient. The main outcome measures were central retinal sensitivity and
      fixation pattern (fixation location and fixation stability) in eyes with
      subfoveal choroidal neovascularization and their relationship to the length of
      disease, type and characteristics of choroidal neovascularization, and visual
      acuity. RESULTS: Of 179 eyes, 135 (75%) had central fixation, 27 (15%) had poor
      central fixation, and 17 (9%) had predominantly eccentric fixation. Seventy-six
      eyes (42%) had stable fixation, 70 eyes (39%) had relatively unstable fixation,
      and 33 eyes (18%) had unstable fixation. In 50 eyes (28%) a dense central scotoma
      was noted. Eighty-nine of 100 eyes (89%) with length of symptoms of less than 3
      months had predominantly central fixation and 58 (58%) had stable fixation; 14 of
      34 eyes (41%) with length of symptoms of more than 6 months had predominantly
      central fixation, and 5 eyes (15%) had stable fixation. In 15 eyes of patients
      who elected not to receive treatment, successive scanning laser ophthalmoscope
      microperimetry were obtained over time (follow-up of 18 months after onset of
      symptoms). Three months or less after the onset of symptoms, 13 eyes (87.7%) had
      predominantly central fixation and 9 eyes (60%) had stable fixation. More than 3
      months and 6 months or less after the onset of symptoms, 10 eyes (66.7%) had
      predominantly central fixation and 7 eyes (46.7%) had stable fixation. This trend
      was further demonstrated in eyes more than 6 months after the onset of symptoms.
      CONCLUSIONS: We conclude that the sequence of events leading to visual function
      deterioration appears to involve an initial mild decrease in central retinal
      sensitivity and visual acuity followed by progressive fixation instability and,
      ultimately, development of an absolute central scotoma with totally eccentric
      fixation. Increased length of disease is associated with worse fixation pattern
      and retinal sensitivity deterioration as assessed by scanning laser
      ophthalmoscope microperimetry. A better understanding of the characteristics of
      visual loss assessed by fixation pattern evaluation and microperimetry in age
      related macular degeneration may help optimize timing, patient selection, and
      treatment options in eyes with this condition.

PMID- 14644218
TI  - Acquired external punctal stenosis: etiology and associated findings.
AB  - PURPOSE; To investigate the underlying causes of acquired external punctal
      stenosis (AEPS) and assess the associated tear drainage problems. DESIGN:
      Prospective, noncomparative observational case series. METHODS: Seventy-eight
      eyes of 52 patients with symptomatic AEPS were prospectively assessed by or under
      supervision of a consultant oculoplastic surgeon from June 1999 to October 2002.
      The severity of the stenosis was graded on clinical examination. Associated
      findings from ophthalmic examination, diagnostic probing, and irrigation were
      recorded. The chi(2) test with 95% confidence interval (CI) and the Fisher exact
      test were used for statistical analysis. RESULTS: The age range was 39 to 90
      years (mean, 69.4 years). Acquired external punctal stenosis was due to chronic
      blepharitis in 35 eyes (45%), unknown etiology in 21 eyes (27%), ectropion in 18
      eyes (23%), and related to drugs in 4 eyes (5%). Associated canalicular stenosis
      and common canalicular stenosis with obstruction (at the level of the internal
      punctum) was found in 36 eyes (46%) with AEPS. Nasolacrimal duct stenosis (5
      eyes) or obstruction (2 eyes) was found in 8.5%. The number of patients with
      associated canalicular and common canalicular stenosis increased with increasing
      age (95% Confidence Interval [CI] = 0.03-0.04, P =.03) and duration of symptoms
      (95% CI = 0.02-0.03, P =.02). The number of patients with associated nasolacrimal
      duct stenosis and obstruction increased with increasing age (95% CI = 0.000-
      0.001, P =.001) and in AEPS with unknown etiology (95% CI = 0.004-0.006, P
      =.003). CONCLUSIONS: Chronic blepharitis is a common cause of AEPS even after
      treating the blepharitis, but in a significant number of patients there is no
      apparent etiology. Associated upper and lower tear drainage stenosis should be
      considered in the preoperative evaluation and surgical plan for AEPS.

PMID- 14644219
TI  - A novel technique for self-sealing, wedge-shaped pars plana sclerotomies and its
      features in ultrasound biomicroscopy and clinical outcome.
AB  - PURPOSE: To investigate a new type of self-sealing pars plana sclerotomy
      clinically and by means of ultrasound biomicroscopy and to compare the outcome
      with conventionally sutured sclerotomies. DESIGN: Prospective, nonrandomized
      clinical trial. METHODS: Twenty-one patients underwent pars plana vitrectomy
      either with (control group) or without suturing (study group) at the Institute of
      Ophthalmology, University Medical Centre Nijmegen, The Netherlands, between
      January 1 and March 31, 2002. One day and 6 to 8 weeks postoperatively, the
      sclerotomy sites were studied by clinical examination and ultrasound
      biomicroscopy. Results were graded according to verbal descriptor scales.
      RESULTS: The study included 21 patients scheduled for pars plana vitrectomy of
      one eye. Mean follow-up time was 6.5 weeks (range, 6-8). Three patients were lost
      to follow-up. Of the remaining patients, 12 had self-sealing wedge-sclerotomies
      and six were conventionally operated. No intraoperative complications occurred in
      any participant and no visual loss or postoperative hypotony was observed. On the
      first day after surgery there was significantly more scleral dehiscence in the
      control group (P =.012). This divergence disappeared during the follow-up period.
      All other differences noticed were not statistically significant. CONCLUSIONS:
      Our novel technique of sutureless wedge-shaped sclerotomy allows the creation of
      simple, reliable, and self-sealing pars plana openings. Clinical examination and
      assessment by ultrasound biomicroscopy showed results to be at least as safe as
      conventionally sutured sclerotomies. This new method allows stable intraoperative
      ocular pressure conditions and seems promising.

PMID- 14644220
TI  - The prevalence of glaucoma in patients with sleep apnea syndrome: same as in the
      general population.
AB  - PURPOSE: An association of glaucoma and sleep apnea syndrome (SAS) has been
      widely reported. We investigated the largest group of patients with SAS thus far
      to determine the prevalence of glaucoma among these patients. DESIGN: Cross
      sectional study. METHODS: An institutional study. STUDY POPULATION: A total of
      228 patients with SAS. OBSERVATION PROCEDURES: Sleep studies determined the
      respiratory disturbance index (RDI) during night sleep. Ocular examination
      included intraocular pressure (IOP) measurement, optic disk evaluation, and
      Humphrey visual field examination. MAIN OUTCOME MEASURES: The SAS was diagnosed
      as an RDI > 10. The RDI was graded to determine the severity of SAS: mild (RDI,
      10-19), moderate (RDI, 20-39), and severe (RDI > 40). Open-angle glaucoma was
      diagnosed when a glaucomatous visual field defect matched the optic disk changes,
      irrespective of IOP levels. RESULTS: Nineteen participants had mild SAS (mean +/-
      standard deviation, RDI = 15 +/- 3), 129 had moderate SAS (RDI = 28 +/- 5), and
      80 had severe SAS (RDI = 54 +/- 11). Open-angle glaucoma was found in five SAS
      subjects, a prevalence of 2% (95% confidence interval, 0.7% to 5%). There was no
      correlation between RDI and the presence of glaucoma (chi-square = 1.18; degrees
      of freedom = 2; P =.6) or between the RDI and the IOP (r = -0.067; P =.316).
      CONCLUSION: The prevalence of glaucoma in SAS patients was similar to that in the
      general Caucasian population.

PMID- 14644221
TI  - Efficacy and safety of ketotifen fumarate 0.025% in the conjunctival antigen
      challenge model of ocular allergic conjunctivitis.
AB  - PURPOSE: To determine the duration of action of ketotifen 0.025% eye drops vs
      placebo taken as single or multiple doses in an allergen challenge model. DESIGN:
      Two randomized, multicenter, double-masked, contralateral placebo-controlled
      studies, one a single-dose and one a multiple-dose study. METHODS: Two
      conjunctival provocation tests (CPTs) were initially conducted to confirm
      reproducibility of subject responses in both studies. Subjects in study 1 (n =
      87) received single doses of ketotifen in one eye and placebo in the other 15
      minutes, 6 hours, and 8 hours before CPT. Subjects in study 2 (n = 85) received
      ketotifen or placebo once 8 hours before CPT. Single-dose efficacy results were
      used to further qualify a subject as a responder. Responders were re-randomized
      to a 4-week twice daily dosing regimen with a CPT 8 hours after the final dose.
      In both studies, ocular symptoms were assessed at three time points 3 to 15
      minutes after challenge. There were no significant differences in adverse events
      between groups. RESULTS: For both studies, ocular itching and vascular injection
      were significantly reduced (P <.003) at all time points after instillation of
      ketotifen, with a maximum reduction at 7 minutes postchallenge. In study 2,
      chemosis, tearing, and lid swelling were also assessed and were significantly
      reduced (P <.008) after instillation of ketotifen. CONCLUSIONS: Ketotifen 0.025%
      eye drops were safe and statistically effective in preventing ocular itching,
      injection, and other signs and symptoms of allergic conjunctivitis at 15 minutes,
      6 hours, and 8 hours after a single dose and at 8 hours after the final dose of a
      4-week twice daily regimen.

PMID- 14644222
TI  - Pulsatile ocular blood flow in primary open-angle glaucoma and ocular
      hypertension.
AB  - PURPOSE: To compare pulsatile ocular blood flow measurements in untreated ocular
      hypertensive (OHT) subjects and primary open-angle glaucoma (POAG) patients.
      DESIGN: A prospective observational study in an institutional setting. METHODS: A
      total of 97 subjects were recruited to the study (50 ocular hypertensives, 24
      glaucoma patients, and 23 normal subjects). "High-risk" OHT had intraocular
      pressure (IOP) > 25 mm Hg; "low-risk" OHT had IOP <or= 25 mm Hg. Pulsatile ocular
      blood flow (POBF) measurements were made with a pneumotonometer in sitting,
      standing, and supine positions. Intraocular pressure was measured with Goldmann
      tonometry. Twenty-six patients were started on topical treatment to reduce
      intraocular pressure, and the measurements were repeated at a review visit.
      RESULTS: Untreated POAG patients and high-risk OHT had reduced POBF (P <.001) and
      pulse volume (P <.001) compared with both normals and low-risk OHT. Women had
      higher POBF than men (P =.009, two-way analysis of variance). Subjects with
      pharmacologically lowered IOP had a significant increase in mean POBF (+80.9
      microl/min, P =.02) and a significant reduction in mean arterial blood pressure (
      11.0 mm Hg, P =.003). Postural reduction in POBF (from sitting to supine)
      increased and became statistically significant in POAG and OHT subjects on
      treatment (P <.0001). CONCLUSION: High-risk ocular hypertensives have reduced
      POBF when compared with low-risk ocular hypertensives and normals and do not
      differ significantly from POAG patients. Our findings support the clinical
      impression that ocular hypertensive subjects with IOP of over 25 mm Hg should be
      monitored closely and may benefit from prophylactic treatment to lower
      intraocular pressure.

PMID- 14644223
TI  - Childhood-onset uveitis in Behcet disease:a descriptive study of 36 cases.
AB  - PURPOSE: To describe the demographic and clinical features, complications,
      treatment, and visual results in patients with childhood-onset Behcet uveitis.
      DESIGN: Observational case series. METHODS: A retrospective study was made of 36
      consecutive patients with Behcet disease seen at the Uveitis Service, Department
      of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, between
      January 1975 and January 2002. Inclusion criteria were fulfillment of the
      classification criteria of the International Study Group for Behcet Disease and
      onset of uveitis at 16 years of age or younger. The medical records of 36
      patients with childhood-onset Behcet uveitis were reviewed. The main outcome
      measures were sex, age at onset of uveitis, the initial symptom of Behcet
      disease, clinical ocular features, ocular complications, systemic treatment,
      complications of treatment, and final visual acuity. RESULTS: Twenty-five
      patients were male, 11 were female. Mean age at onset of uveitis was 13.6 years.
      The initial symptom was oral ulcer in 63.8% of the patients. The majority of
      patients (83.3%) had bilateral involvement. Panuveitis was the most common form
      (86.2%). Retinal vasculitis and retinitis were the most common ocular findings
      seen in 83.3% and 68.2% of the involved eyes, respectively. Cataract,
      maculopathy, and optic atrophy were the most common complications seen in 46.9%,
      45.4%, and 39.4% of the involved eyes, respectively. Immunosuppressive therapy
      was administered to 75% of the patients. Response to treatment was variable. The
      most common complications of systemic treatment were associated with
      corticosteroid therapy. Final visual acuity was worse than 0.1 in 22.7% of the
      involved eyes. CONCLUSIONS: Childhood-onset Behcet uveitis was more common among
      males. Bilateral panuveitis with retinal vasculitis and retinitis was the most
      common form of ocular involvement, similar to the adult patient. The treatment is
      challenging, as the use oral corticosteroids is associated with significant
      complications and the response to conventional immunosuppressive therapy is
      variable.

PMID- 14644224
TI  - Comparison of measurements of refractive errors between the hand-held Retinomax
      and on-table autorefractors in cyclopleged and noncyclopleged children.
AB  - PURPOSE: To compare the measurement of refractive errors (sphere, cylinder, and
      axis) between the hand-held Retinomax and on-table Topcon autorefractors in
      cyclopleged and noncyclopleged young children. The average bias and measurement
      agreement were assessed. DESIGN: Observational cross-sectional study. METHODS:
      The study included 114 cyclopleged and 156 noncyclopleged young children. The
      mean difference between the two methods and the 95% limits of agreement were
      calculated to evaluate the average bias. Two types of analyses were conducted to
      assess the degree of agreement. First, the proportion of the absolute mean
      differences was presented in different ranges (<or=0.25, 0.25-0.5, 0.5-0.75, 0.75
      1.0, and >1.0 diopters for sphere and cylinder; 0-10, 11-20 and >20 degrees for
      axis). Second, the paired t test was conducted to evaluate the consistency of two
      types of measurements. RESULTS: The data by the Retinomax had mild bias (0.59
      diopters) toward a lower sphere data under noncycloplegia but no bias under
      cycloplegia. For cylinder and axis, there was either no bias or clinically
      acceptable bias (0.02-0.13 diopters for cylinder and 2-7 degrees for axis)
      regardless of cycloplegia. Besides the sphere data under noncycloplegia, in
      general 90% of the mean differences of sphere and cylinder were within 0.5
      diopters. More than 97% of the difference in axis under cycloplegia and 68% under
      noncycloplegia were within 20 degrees. After adjusting for mild bias, the paired
      t test showed very consistent results. CONCLUSIONS: The data by the Retinomax
      were consistent with those by the Topcon. The Retinomax is a useful instrument to
      screen refractive errors in young children.

PMID- 14644225
TI  - Benefits of electronic vision enhancement systems (EVES) for the visually
      impaired.
AB  - PURPOSE: To examine whether objective performance of near tasks is improved with
      various electronic vision enhancement systems (EVES) compared with the subject's
      own optical magnifier. DESIGN: Experimental study, randomized, within-patient
      design. METHODS: This was a prospective study, conducted in a hospital
      ophthalmology low-vision clinic. The patient population comprised 70 sequential
      visually impaired subjects. The magnifying devices examined were: patient's
      optimum optical magnifier; magnification and field-of-view matched mouse EVES
      with monitor or head-mounted display (HMD) viewing; and stand EVES with monitor
      viewing. The tasks performed were: reading speed and acuity; time taken to track
      from one column of print to the next; follow a route map, and locate a specific
      feature; and identification of specific information from a medicine label.
      RESULTS: Mouse EVES with HMD viewing caused lower reading speeds than stand EVES
      with monitor viewing (F = 38.7, P <.001). Reading with the optical magnifier was
      slower than with the mouse or stand EVES with monitor viewing at smaller print
      sizes (P <.05). The column location task was faster with the optical magnifier
      than with any of the EVES (F = 10.3, P <.001). The map tracking and medicine
      label identification task was slower with the mouse EVES with HMD viewing than
      with the other magnifiers (P <.01). Previous EVES experience had no effect on
      task performance (P >.05), but subjects with previous optical magnifier
      experience were significantly slower at performing the medicine label
      identification task with all of the EVES (P <.05). CONCLUSIONS: Although EVES
      provide objective benefits to the visually impaired in reading speed and acuity,
      together with some specific near tasks, some can be performed just as fast using
      optical magnification.

PMID- 14644226
TI  - Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and
      thermolabile MTHFR genotype as risk factors for retinal vascular occlusive
      disease.
AB  - PURPOSE: To assess the role of plasma total homocysteine (tHcy) levels, serum
      folate and vitamin B(12)levels, and homozygosity for the thermolabile
      methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal
      vascular occlusive disease. DESIGN: Meta-analysis of literature. METHODS: A
      MEDLINE search was performed to identify all published case-control studies of
      plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in
      persons with retinal vascular occlusive disease. Main outcome measures included
      calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard
      differences and odds ratios (OR) of TT genotype between cases and controls.
      RESULTS: In total, 614 patients with all types of retinal vein occlusion had
      higher plasma tHcy levels than 762 control subjects (standard difference, 0.867;
      95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were
      also higher in 154 patients with retinal artery occlusion compared with 358
      control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001).
      Serum folates, but not vitamin B(12) levels, were lower in 287 patients with
      retinal vascular occlusion than in the same number of control subjects (standard
      difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024,
      0.104; P =.474, respectively). Similar proportions of 690 patients with retinal
      vein occlusion and 2754 control subjects demonstrated the TT genotype (OR =
      1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery
      occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060).
      CONCLUSIONS: Retinal vascular occlusion is associated with elevated plasma tHcy
      levels and low serum folate levels, but not serum vitamin B(12) levels and TT
      genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels
      and serum folate levels should be determined in patients with retinal vascular
      occlusions, and dietary supplementation with low doses of folate and vitamin
      B(12) should be considered for affected persons.

PMID- 14644227
TI  - Antibody-targeted photodynamic therapy.
AB  - PURPOSE: To assess the feasibility of conjugation of verteporfin (Visudyne,
      Parkedale Pharmaceuticals, Rochester, Minnesota, USA) to antibody against
      vascular endothelial growth factor. DESIGN: Experimental study. METHODS: Rabbit
      antimouse vascular endothelial growth factor polyclonal antibody was conjugated
      to verteporfin. Fluorescence excitation-emission spectra of verteporfin and
      conjugate were examined. Vascular endothelial growth factor-expressing murine
      endothelial cells were incubated with saline, verteporfin, or conjugate, followed
      by laser exposure or no laser exposure. Cell viability at 1 and 24 hours was
      assessed via trypan blue exclusion. Results were analyzed by two-way analysis of
      variance with replication and the Bonferroni multiple comparison test. RESULTS:
      The fluorescence excitation-emission spectrum of the conjugate was similar to
      that of verteporfin. After laser exposure, cell viability in conjugate-treated
      cells was reduced to 6% at 1 hour (P <.0001) and to 4% at 24 hours (P <.0001),
      compared with approximately 40% in nonlaser-exposed, conjugate-treated cells. The
      cytotoxicity in the conjugate-treated cells was higher than in verteporfin
      treated cells exposed to laser, although the difference did not reach statistical
      significance. CONCLUSIONS: The conjugation of verteporfin to polyclonal antibody
      is possible without the loss of its photosensitizing properties. Conjugated
      verteporfin destroys cellular targets at least as effectively as verteporfin
      alone.

PMID- 14644228
TI  - Visual impairment and unintentional injury mortality: the National Health
      Interview Survey 1986-1994.
AB  - PURPOSE: To examine the relationship between reported visual impairment and
      unintentional injury mortality. DESIGN: Mortality linkage study of a population
      based survey. METHODS: Mortality linkage through 1997 of 116,796 adult
      participants, aged 18 years and older, from the 1986 to 1994 National Health
      Interview Survey was analyzed with respect to reported visual impairment using
      Cox regression models. The average follow-up was 7.0 years, and 295 unintentional
      injury deaths were identified. After controlling for survey design, age, sex, and
      the presence and number of eye diseases, participants with severe, bilateral
      visual impairment were at increased risk of death relative to participants
      without visual impairment (hazard ratio: 7.4; 95% confidence interval: 3.0-17.8).
      CONCLUSIONS: Our data provide evidence that severe, bilateral visual impairment
      is associated with an increased risk of unintentional mortality among adults in
      the United States.

PMID- 14644229
TI  - Long-term follow-up for bullous keratopathy after sato-type anterior-posterior
      corneal refractive surgery.
AB  - PURPOSE: To evaluate cases of bullous keratopathy resulting from anterior
      posterior radial corneal keratotomy (Sato-type operation) performed from 1951 to
      1959. DESIGN: Observational case series. METHODS: Records for a total of 220 eyes
      of 139 patients with follow-up examinations were examined. The age at operation
      vs time to occurrence of bullous keratopathy after the original operation was
      evaluated in four age groups. Endothelial cell density was measured in 11 long
      term postoperative eyes. RESULTS: The mean time to development of bullous
      keratopathy after surgery was 26.9 +/- 8.8 years (mean +/- SD; n = 173 eyes). The
      length of this period was not affected by the age of the patient at the time of
      the original surgery. Average endothelial cell density in 11 eyes of 11 patients
      28.5 +/- 3.7 years after surgery was 639 +/- 135 cells/mm(2). CONCLUSIONS:
      Although some corneas remained clear more than 26 years after anterior-posterior
      radial keratotomy, the risk of late corneal decompensation continues to exist for
      these patients.

PMID- 14644230
TI  - Delayed suprachoroidal hemorrhage after needle revision of trabeculectomy bleb in
      a patient with hairy cell leukemia.
AB  - PURPOSE: To report a rare complication, delayed suprachoroidal hemorrhage, of
      needle revision of a nonfunctioning trabeculectomy bleb in a patient with
      previously undetected hairy cell leukemia. DESIGN: Interventional case report.
      METHODS; An 89-year-old man presented with massive delayed suprachoroidal
      hemorrhage after needle revision of a trabeculectomy bleb. RESULTS: Routine
      investigations before choriodal drainage showed a low platelet count. Anterior
      chamber washout and choroidal drainage were done after intravenous platelet
      infusions. Subsequently, the diagnosis of hairy cell leukemia was made by the
      hematologist. CONCLUSIONS: Delayed suprachoroidal hemorrhage is a rare but
      devastating complication of needle revision of trabeculectomy blebs and should be
      borne in mind while performing this seemingly trivial outpatient procedure.

PMID- 14644231
TI  - Presumed combined hamartoma of the retina and retinal pigment epithelium with
      preretinal neovascularization.
AB  - PURPOSE: To describe a case of presumed combined hamartoma of the retina and
      retinal pigment epithelium associated with preretinal neovascularization. DESIGN:
      Observational case report. METHODS: We report clinical and angiographic findings
      of a 26-year-old woman. RESULTS: The patient presented with mild vitreous
      hemorrhage and slowly decreasing vision in the right eye. A combined hamartoma of
      the midperipheral retina and retinal pigment epithelium with an epiretinal
      membrane causing traction to the macula was found. Fluorescein angiography showed
      areas of capillary nonperfusion and a large preretinal neovascularization
      peripheral to the hamartoma. CONCLUSIONS: A combined hamartoma may be associated
      with retinal capillary nonperfusion and preretinal neovascularization, suggesting
      that significant retinal ischemia can occur with a combined hamartoma.

PMID- 14644232
TI  - Acanthamoeba keratitis as a complication of orthokeratology.
AB  - PURPOSE: To present four cases of Acanthamoeba keratitis as a complication of
      orthokeratology. DESIGN: Observational case report. METHODS: Four patients with
      Acanthamoeba keratitis had histories of overnight orthokeratology lens wear of 6
      months to 2 years. RESULTS: Three cases were diagnosed with Acanthamoeba
      keratitis by corneal scraping and one by confocal microscopy examination. The
      patients were treated with chlorhexidine, metronidazole, and neomycin sulfate,
      resulting in a rapid resolution of ocular inflammation. CONCLUSION: Overnight
      wear of orthokeratology lenses may induce Acanthamoeba keratitis.

PMID- 14644234
TI  - Multifocal electroretinogram in branch retinal vein occlusion.
AB  - PURPOSE: To describe the response from multifocal electroretinography in branch
      retinal vein occlusion. DESIGN: Prospective observational case control series.
      METHODS: Multifocal electroretinography was recorded in 15 patients with temporal
      branch retinal vein occlusion and 21 control subjects using a visual evoked
      response imaging system. RESULTS: There were significant differences in mean
      amplitude (P =.01) and latency (P =.001) between thrombotic and nonthrombotic
      retina in the same eyes, as well as in patients compared with control subjects.
      CONCLUSION: Responses from multifocal electroretinography demonstrate retinal
      dysfunction in branch retinal vein occlusion; additional studies will demonstrate
      whether multifocal electroretinography has a prognostic value.

PMID- 14644233
TI  - Wavefront analysis in eyes with accommodative spasm.
AB  - PURPOSE: To investigate changes of spherical aberration in eyes with
      accommodative spasm. DESIGN: Case reports. METHODS: Four eyes of two patients
      with accommodative spasm were studied. Ocular spherical aberration was measured
      with a Hartmann-Shack wavefront aberrometer for the central 4-mm zone. RESULTS:
      The root mean square values of spherical aberration were negative (-0.086 +/-
      0.026 microm root mean square). However, when the spasm of accommodation was
      cured or treated with a cycloplegic agent, the value shifted toward positivity
      (0.025 +/- 0.004 microm root mean square). CONCLUSIONS: Excessive accommodative
      tone is manifested objectively by negative spherical aberration in eyes with
      accommodative spasm.

PMID- 14644235
TI  - Macular hole closure after peribulbar steroid injection.
AB  - PURPOSE: To report the closure of a macular hole after a peribulbar
      corticosteroid injection in a patient with anterior uveitis associated with human
      leukocyte antigen B*27. DESIGN: Interventional case report.The patient was
      evaluated by comprehensive ophthalmic check-up and optical coherence tomography.
      RESULTS: A healthy 50-year-old woman presented to our service with active human
      leukocyte antigen B*27-associated anterior uveitis, macular hole in the right eye
      and macular edema in the left eye. Visual acuity was 20/200 in both eyes.
      Peribulbar injections of triamcinolone acetonide were administered in both eyes.
      Three months later, visual acuity improved to 20/50 in both eyes, and the uveitis
      was in complete remission. Optical coherence tomography verified that the macular
      hole in the right eye was closed. CONCLUSIONS: Inflammation and macular edema
      might be contributing factors in macular hole formation in patients with uveitis.
      This case indicates that treatment of inflammation and macular edema might lead
      to macular hole closure in similar cases.

PMID- 14644236
TI  - Optical coherence tomographic observations before and after macular hole
      formation secondary to laser injury.
AB  - PURPOSE: To describe the ophthalmoscopic and optical coherence tomographically
      determined retinovitreous interface before and after the development of a macular
      hole secondary to an accidental laser injury. DESIGN: Observational case report.
      METHODS: Ophthalmoscopic and optical coherence tomography (OCT) findings in a 53
      year-old man were evaluated before and after the macular hole formation secondary
      to a laser injury. Visual function was followed for 9 months after surgery.
      RESULTS: A 53-year-old man sustained injury to his right eye by a Ti: Sapphire
      laser. On the following day, his corrected visual acuity was 0.3, and a small
      pigment epithelial atrophy was present in the right foveal area. No macular hole
      was detected by OCT and the retinovitreal interface was normal. Fifty-three days
      later, a full-thickness macular hole appeared, and no posterior vitreous
      detachment was detected by OCT. The hole was closed by surgery with final best
      corrected visual acuity of 0.7. CONCLUSIONS: Macular holes can develop without
      visible traction on the retina and can occur long after retinal injury.

PMID- 14644237
TI  - The association of autosomal dominant optic atrophy and moderate deafness may be
      due to the R445H mutation in the OPA1 gene.
AB  - PURPOSE: To examine the involvement of the optic atrophy 1 (OPA1) gene in optic
      atrophy associated with moderate deafness. DESIGN: Observational case report. The
      entire coding sequence of the OPA1 gene was directly sequenced in the case of a
      patient suffering from optic atrophy associated with moderate deafness. RESULTS:
      A de novo heterozygous mutation R445H in the OPA1 gene was found. No similar
      mutation was detected in either of the patient's parents or in the 100 chromosome
      controls. CONCLUSION: The R445H mutation in OPA1 might be the cause of the
      association between dominant optic atrophy and moderate deafness, a phenotype
      that may be currently underdiagnosed.

PMID- 14644238
TI  - Nonarteritic anterior ischemic optic neuropathy and surgery of the anterior
      segment: temporal relationship analysis.
AB  - PURPOSE: This study analyzes the temporal relationship between intraocular lens
      surgery and nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN:
      Retrospective cohort study. METHODS: Eighteen cases of NAION in 17 subjects
      occurring within 1 year after lens-related surgery were identified with a
      retrospective review of patients diagnosed with NAION. The temporal relationship
      between NAION onset and surgery was evaluated by using an exact chi-square test
      of goodness of fit to compare the observed with a uniform distribution, which
      would be expected if intraocular surgery were not causal. RESULTS: All 18 cases
      occurred within 6 months of surgery (mean interval, 35 days; range, 1-130 days),
      which is significantly different from a uniform distribution (P <.001).
      CONCLUSION: Our data indicate that intraocular lens surgery is associated with
      the occurrence of NAION.

PMID- 14644239
TI  - Nonpenetrating filtering surgery and goniopuncture (staged trabeculectomy) for
      episcleral venous pressure glaucoma.
AB  - PURPOSE: To report long-term (>5 years) success of non-penetrating filtering
      surgery in glaucoma due to elevated episcleral venous pressure. DESIGN:
      Observational case report. METHODS: A 25-year-old woman developed severe glaucoma
      due to elevated episcleral venous pressure. Nonpenetrating filtering surgery
      (opening of the Schlemm canal and resection of corneal stroma overlying the
      trabecular meshwork and Descemet membrane) was performed with mitomycin. Three
      months later, the meshwork was perforated ab interno by neodymium:yttrium
      aluminum-garnet laser via goniolens (goniopuncture). RESULTS: There were no
      complications, and no glaucoma medications were used postoperatively. Intraocular
      pressure ranged from 10 mm Hg to 18 mm Hg during the first 4 months and
      thereafter between 6 mm Hg and 12 mm Hg. CONCLUSIONS: Glaucoma due to elevated
      episcleral venous pressure, an entity associated with significant trabeculectomy
      risks, can be safely and successfully treated with non-penetrating filtering
      surgery followed by goniopuncture (staged trabeculectomy).

PMID- 14644240
TI  - Residual triamcinolone acetonide in the macular hole after vitrectomy.
AB  - PURPOSE: To report a case of vitrectomy using intraocular triamcinolone acetonide
      (TA), in which TA remained in the macular hole after surgery. DESIGN:
      Observational case report. METHODS: A 60-year-old Japanese man had a Stage II
      macular hole in the right eye with best-corrected visual acuity of 20/50. A pars
      plana vitrectomy using TA was performed. Visual acuity and anatomic results were
      followed up for a period of 8 weeks. RESULTS: On the sixth postoperative day,
      residual TA deposition was observed in the macular hole. On the 14th
      postoperative day, no residual TA was found and the macular hole was successfully
      closed. The best-corrected visual acuity of the right eye improved to 20/15.
      CONCLUSIONS: Residual TA in the macular hole after vitrectomy did not interfere
      with macular hole repair either anatomically or functionally.

PMID- 14644241
TI  - Long anterior zonules and pigment dispersion.
AB  - PURPOSE: To describe pigment dispersion associated with long anterior zonules.
      DESIGN: Multicenter observational case series. METHODS: Fifteen patients, seven
      of whom were treated for glaucoma or ocular hypertension, were identified with
      long anterior zonules and pigment dispersion. Transmission electron microscopy
      was performed on one anterior capsule specimen. RESULTS: All patients had
      anterior zonules that inserted centrally on the lens capsule. Signs of pigment
      dispersion included corneal endothelial pigmentation, loss of the pupillary ruff,
      and variable trabecular meshwork pigmentation. Ultrasound biomicroscopy verified
      the lack of posterior iris insertion and concavity. There was no exfoliation
      material. Transmission electron microscopy showed zonular lamellae with adherent
      pigment granules, and no exfoliation material. CONCLUSIONS: Long anterior zonules
      inserted onto the central lens capsule may cause mechanical disruption of the
      pigment epithelium at the pupillary ruff and central iris leading to pigment
      dispersion.

PMID- 14644242
TI  - Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization
      in best disease.
AB  - PURPOSE: To describe the effects of photodynamic therapy using verteporfin for
      the treatment of subfoveal choroidal neovascularization (CNV) in Best vitelliform
      macular dystrophy. DESIGN: Interventional case report. METHODS: A 43-year-old
      patient with confirmed Best vitelliform macular dystrophy complicated with
      subfoveal CNV received a single photodynamic therapy session with verteporfin.
      The patient was prospectively followed with fluorescein angiography and optical
      coherence tomography. RESULTS: A regression of the neovascular lesion and
      resolution of the exudative manifestations was observed 3 weeks after treatment;
      at that time, visual acuity had improved from 20/60 to 20/25. Optical coherence
      tomography disclosed restoration of normal macular architecture due to fluid
      resolution and lesion contraction. Up to 2 years from this single treatment, no
      further change was observed. CONCLUSIONS: Regression of CNV and resolution of
      subretinal hemorrhage as well as exudative manifestations occurred after
      photodynamic therapy with verteporfin. Verteporfin therapy may be a viable
      treatment for subfoveal neovascular lesions in Best vitelliform macular
      dystrophy.

PMID- 14644243
TI  - Bilateral central retinal artery occlusion in Churg-Strauss syndrome.
AB  - PURPOSE: To describe a rare bilateral central retinal artery occlusion in a
      patient with Churg-Strauss syndrome. DESIGN: Observational case report. METHODS:
      A 68-year-old Japanese man with Churg-Strauss syndrome developed sudden vision
      loss in both eyes. Medical history included bronchial asthma, elevated
      eosinophils, and aortic regurgitation. RESULT: Central retinal artery occlusion
      was diagnosed by retinal whitening, a cherry-red spot, and delayed arteriovenous
      transit time on fluorescein angiography. Corticosteroids, cyclophosphamide, and
      anticoagulant therapy altered the hypereosinophilia and mononeuritis multiplex,
      but no visual recovery occurred during the following 2 years. CONCLUSION:
      Bilateral central retinal artery occlusion can occur in Churg-Strauss syndrome.
      Patients with this diagnosis should be carefully followed.

PMID- 14644244
TI  - West Nile virus-associated optic neuritis and chorioretinitis.
AB  - PURPOSE: To report the new ocular and neurologic features of West Nile virus
      (WNV) meningoencephalitis. DESIGN: Observational case report. METHODS: A 55-year
      old woman presented with headache, stiff neck, visual loss, and fever 10 days
      after a weekend camping trip. Examination revealed vitritis, creamy yellow
      circular chorioretinal lesions, and peripheral visual field loss. RESULTS:
      Laboratory investigation indicated the patient was suffering from WNV
      meningoencephalitis with neuro-ocular involvement. CONCLUSION: Ophthalmologists
      and infectious disease specialists should recognize that the WNV infection
      spectrum may include ophthalmic findings, specifically optic neuritis and
      multifocal chorioretinitis.

PMID- 14644245
TI  - Central retinal vein occlusion and renal cell carcinoma.
AB  - PURPOSE: To document a case of central retinal vein occlusion (CRVO) associated
      with renal cell carcinoma and elevated levels of anticardiolipin and
      antiphospholipid antibodies. DESIGN: Observational case report. METHODS: History,
      clinical examination, chart review, and laboratory serologies were performed on a
      63-year-old man with renal cell carcinoma with a 6-week history of decreased
      vision in his left eye. RESULTS: Vision was 20/40 in the left eye. Dilated fundus
      examination revealed a CRVO. Laboratory serologies revealed markedly elevated
      levels of anticardiolipin and antiphospholipid antibodies. CONCLUSION: This case
      illustrates an association between CRVO and renal cell carcinoma. A
      paraneoplastic process, consisting of both antiphospholipid and anticardiolipin
      antibodies, may be a mechanism for CRVO.

PMID- 14644246
TI  - A case of Kniest dysplasia with retinal detachment and the mutation analysis.
AB  - PURPOSE: To report a case of Kniest dysplasia with retinal detachment associated
      with a novel type II collagen gene (COL2A1) mutation. DESIGN: Interventional case
      report. METHODS: DNA was isolated from peripheral lymphocytes, and mutational
      analysis was carried out using polymerase chain reaction and direct sequencing.
      RESULTS: A 14-year-old Japanese boy was diagnosed with Kniest dysplasia, and
      ophthalmic examination revealed a retinal detachment in the right eye. He was
      successfully treated by vitrectomy and silicon oil injection, and his visual
      acuity improved from 0.01 to 0.22. DNA analysis of COL2A1 revealed a single base
      pair substitution at position +5 of intron 20. CONCLUSION: Vitrectomy and silicon
      oil injection were effective in reattaching the retinal detachment in a Kniest
      dysplasia patient. The genetic alteration found in this patient suggested that
      this prevented the normal splicing of COL2A1, resulting in an abnormal type II
      collagen product.

PMID- 14644247
TI  - Conjunctival melanoma: is it increasing in the United States?

PMID- 14644249
TI  - Conjunctival melanoma: is it increasing in the United States?

PMID- 14644251
TI  - A new, non-contact wide-field viewing system for vitreous surgery.

PMID- 14644253
TI  - Dosage of intravitreal triamcinolone.

PMID- 14644255
TI  - Perspectives on diabetic retinopathy.

PMID- 14644257
TI  - Indocyanine green-assisted peeling of the internal limiting membrane in macular
      hole surgery affects visual outcome.

PMID- 14644259
TI  - The effect of optic disk edema on spontaneous venous pulsations.

PMID- 14644275
TI  - Optimization of operating room allocation using linear programming techniques.
AB  - BACKGROUND: New and innovative approaches must be used to rationally allocate
      scarce resources such as operating room time while simultaneously optimizing the
      associated financial return. In this article we use the technique of linear
      programming to optimize allocation of OR time among a group of surgeons based on
      professional fee generation. STUDY DESIGN: For the period of December 1, 2000, to
      July 31, 2002, the following individualized data were obtained for the Division
      of General Surgery at Duke University Medical Center: allocated OR time (hours),
      case mix as determined by CPT codes, total OR time used, and normalized
      professional charges and receipts. Inpatient, outpatient, and emergency cases
      were included. The Solver linear programming routine in Microsoft Excel
      (Microsoft Corp.) was used to determine the optimal mix of surgical OR time
      allocation to maximize professional receipts. RESULTS: Our model of optimized OR
      allocation would maximize weekly professional revenues at 237,523 US dollars, a
      potential increase of 15% over the historical value of 207,700 US dollars or an
      annualized increase of approximately 1.5 million US dollars. CONCLUSIONS: Our
      results suggest that mathematical modeling techniques used in operations
      research, management science, or decision science may rationally optimize OR
      allocation to maximize revenue or to minimize costs. These techniques may
      optimize allocation of scarce resources in the context of the goals specific to
      individual academic departments of surgery.

PMID- 14644276
TI  - Obesity influences outcome of sentinel lymph node biopsy in early-stage breast
      cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy is a rapidly emerging standard of care for
      staging the axilla in invasive breast cancer. Factors influencing success must be
      identified to understand the procedure's limitations and challenges. Increasing
      body mass with age has an inverse relationship to success. A proportion of SLN
      biopsy patients are both senior and overweight, so measurement of the body mass
      to age relationship is essential. STUDY DESIGN: We reviewed mapping successes and
      failures in 2,495 SLN biopsy procedures performed between September 1996 and June
      2001. Clinical stage T1 N0 to T3 N0 breast cancer cases were included. We used a
      combined technique (radioisotope and blue dye) to detect SLNs. Failure was
      defined as the inability to identify any nodes with either blue dye or by in vivo
      counts. Body- mass index (BMI) for each patient was measured by height and weight
      data (kg/m(2)), and cases were stratified by BMI and age. RESULTS: Among 2,495
      cases, there were 62 failed and 2,433 successful mappings (failure rate = 2.48%).
      Mean age, weight, and BMI were significantly higher in the failure group. The
      success of SLN biopsy was inversely related to BMI (r = -0.98, p = 0.002). When
      stratified by patient age (< 50 versus > or =50 years), this relationship was
      more pronounced in the > or = 50 group. Multivariate analysis of age, weight, and
      BMI found age (p = 0.011) and BMI (p = 0.00001) to be predictive of SLN mapping
      success, with weight alone not significant. CONCLUSIONS: Increasing age and BMI
      do not appear to be contraindications for SLN biopsy. Rather, surgeons should be
      aware that increasing body mass and age are potential risk factors for a failed
      procedure, in which case a completion axillary node dissection for staging is
      required.

PMID- 14644277
TI  - Thoracoscopic and laparoscopic esophagectomy for benign and malignant disease:
      lessons learned from 46 consecutive procedures.
AB  - BACKGROUND: Transhiatal and transthoracic esophagectomy are common approaches for
      esophageal resection. The literature is limited regarding the combined
      thoracoscopic and laparoscopic approach to esophagectomy. The aim of this study
      was to evaluate the outcomes of combined thoracoscopic and laparoscopic
      esophagectomy for the treatment of benign and malignant esophageal disease. STUDY
      DESIGN: We performed a retrospective chart review of 46 consecutive minimally
      invasive esophagectomies performed between August 1998 and September 2002.
      Indications for esophagectomy were carcinoma (n = 38), Barrett's esophagus with
      high-grade dysplasia (n = 3), and recalcitrant stricture (n = 5). Of 38 patients
      with carcinoma 23 (61%) had neoadjuvant therapy. The main outcome measures were
      operative time, blood loss, length of intensive care unit and hospital stay,
      conversion rate, morbidity, mortality, pathology, disease recurrence, and
      survival. RESULTS: Approaches to esophagectomy were thoracoscopic and
      laparoscopic esophagectomy (n = 41), thoracoscopic and laparoscopic Ivor Lewis
      resection (n = 3), abdominal only laparoscopic esophagogastrectomy (n = 1), and
      hand-assisted laparoscopic transhiatal esophagectomy (n = 1). Minimally invasive
      esophagectomy was successfully completed in 45 (97.8%) of 46 patients. The mean
      operative time was 350 +/- 75 minutes and the mean blood loss was 279 +/- 184 mL.
      The median length of intensive care unit stay was 2 days and median length of
      stay was 8 days. Major complications occurred in 17.4% of patients and minor
      complications occurred in 10.8%. Late complications were seen in 26.1% of
      patients. The overall mortality was 4.3%. Among the 38 patients who underwent
      esophagectomy for cancer the 3-year survival was 57%. In a mean followup of 26
      months there was no trocar site or neck wound recurrences. CONCLUSIONS: A
      thoracoscopic and laparoscopic approach to esophagectomy is technically feasible
      and safe for the treatment of benign and malignant esophageal disease. With a
      mean followup of 26 months thoracoscopic and laparoscopic esophagectomy appears
      to be an oncologically acceptable surgical approach for the treatment of
      esophageal cancer.

PMID- 14644278
TI  - Outcomes of active operation during intensive followup for second primary
      malignancy after esophagectomy for thoracic squamous cell esophageal carcinoma.
AB  - BACKGROUND: Recent advances in the treatment of thoracic esophageal cancer have
      afforded it a better prognosis. As a consequence, increasing attention is being
      paid to the outcomes with postoperative monitoring for second primary
      malignancies after esophagectomy, but no recent study has focused on the longterm
      followup and outcomes in these patients. STUDY DESIGN: In 1989, we began
      intensive prospective screening and surveillance designed to detect cancers of
      the head and neck, lung, stomach, residual esophagus, and colon/rectum after
      esophagectomy. Between 1989 and 2001, 365 patients underwent esophagectomy for
      thoracic squamous cell esophageal carcinoma in our department. Of those, 200 were
      followed up as part of this program. Excluded were patients in whom esophageal
      cancer recurred, patients with other prior or simultaneous malignancies, and
      patients who died within a year of operation. Clinicopathologic profiles and
      treatment outcomes were determined for 33 patients who developed a second primary
      malignancy after esophagectomy. RESULTS: The interval between the primary
      esophageal cancer and the secondary carcinoma was 49 +/- 40 months (median, 48
      months). The second primary malignancies were located in the stomach (30%), head
      and neck (24%), lung (24%), colon/rectum (9%), liver (6%), pancreas (3%), and
      blood (6%). Twenty-one patients (64%) were classified as stage 0, I, or II; 10
      (30%) were stage III or IV. Overall, the 2-year, 3-year, and 5-year survival
      rates following diagnosis of a second primary malignancy were 58.0%, 58.0%, and
      48.6%, respectively. Of the 19 patients (58%) in whom second primary malignancies
      were detected before symptoms developed, the 5-year survival rate was 70.7%,
      which was significantly greater than that among patients whose secondary
      malignancies were discovered after symptoms developed (17.1%). CONCLUSIONS: Good
      outcomes in the treatment of second primary malignancies after esophagectomy for
      thoracic squamous cell esophageal carcinoma can be obtained with longterm,
      intensive followup and active surgical intervention for detected malignancies.

PMID- 14644279
TI  - A metaanalysis of laparoscopic cholecystectomy in patients with cirrhosis.
AB  - BACKGROUND: Few articles address the issue of LC in patients with cirrhosis.
      Existing articles are retrospective and with small sample sizes, which makes it
      difficult to draw conclusions about indications and complications with LC in this
      setting. STUDY DESIGN: An extensive search of the Medline, Embase, and Cochrane
      databases using the terms "laparoscopic cholecystectomy" and "cirrhosis" or
      "cirrhotic" was conducted. The data from each study were extracted, combined with
      those of similar studies, and analyzed. RESULTS: Twenty-five publications (400
      patients with cirrhosis undergoing LC) from 1993 to 2001 were identified. Four
      articles compared LC with open cholecystectomy in patients with cirrhosis, and
      six compared patients with cirrhosis to patients without cirrhosis. Patients were
      primarily in Child-Pugh class A or B, with only six patients in Child-Pugh class
      C. Compared with patients without cirrhosis, patients with cirrhosis had higher
      conversion rates (7.06% versus 3.64%, p = 0.024), operative times (98.2 minutes
      versus 70 minutes, p = 0.005), bleeding complications (26.4% versus 3.1%, p <
      0.001), and overall morbidity (20.86% versus 7.99%, p < 0.001). Acute
      cholecystitis was evident in 47% of patients with cirrhosis versus 14.7% of
      patients without cirrhosis (p < 0.001). When LC was compared with open
      cholecystectomy in patients with cirrhosis, LC was associated with less operative
      blood loss (113 mL versus 425.2 mL, p = 0.015), operative time (123.3 minutes
      versus 150.2 minutes, p < 0.042), and length of hospital stay (6 days versus 12.2
      days, p < 0.001). CONCLUSIONS: Patients with cirrhosis undergo cholecystectomies
      for more emergent reasons and have higher morbidity. The laparoscopic approach
      offers advantages of less blood loss, shorter operative time, and shorter length
      of hospitalization in patients with cirrhosis. Prospective studies will establish
      which factors affect outcomes and determine the appropriateness of LC in Child's
      Pugh class C cirrhosis.

PMID- 14644280
TI  - Preoperative simulation of vascular anatomy by three-dimensional computed
      tomography imaging in laparoscopic gastric cancer surgery.
AB  - BACKGROUND: Treatment of early gastric cancer may be an ideal application for
      laparoscopic surgery. But laparoscopic surgery has various limitations derived
      from the lack of tactile feedback and a two-dimensional display of the operative
      field. So, laparoscopic surgery is technically challenging and requires a more
      detailed understanding of local anatomy than conventional open surgery does. The
      purpose of this study was to evaluate the value of three-dimensional computed
      tomography imaging in the preoperative simulation of laparoscopic gastric cancer
      surgery. STUDY DESIGN: Multidetector-row helical CT was performed preoperatively
      in 49 patients who underwent laparoscopic gastric cancer surgery. Scanning was
      initiated approximately 20 seconds after an intravenous injection of 100 mL of
      contrast material at 5 mL/second. Three-dimensional CT images were reconstructed
      using the volume-rendering technique. RESULTS: 3D-CT imaging depicted the
      stomach, arterial, and venous anatomy and was able to identify important vascular
      variants. Preoperative information concerning the right gastric artery led us to
      the site of its branching and facilitated dissection of suprapyloric lymph nodes.
      The left gastric artery furnishing the aberrant left hepatic artery was
      successfully revealed and this information enabled us to avoid accidental
      hemorrhage and ischemic liver damage. Preoperative confirmation of the drainage
      routes of the left gastric vein was also useful in accomplishing secure
      lymphadenectomy. CONCLUSIONS: 3D-CT imaging provides a vascular "road map," which
      is critical for surgical guidance, and prevents the risks involved in surgery.
      Preoperative 3D-CT imaging may be an informative device to overcome the
      disadvantages of laparoscopic gastric cancer surgery.

PMID- 14644281
TI  - Pancreaticoduodenectomy: a rare procedure for the management of complex
      pancreaticoduodenal injuries.
AB  - BACKGROUND: Pancreaticoduodenectomy (Whipple's procedure) is a formidable
      procedure when undertaken for severe pancreaticoduodenal injury. The purposes of
      this study were to review our experience with this procedure for trauma; to
      classify injury grades for both pancreatic and duodenal injuries in patients
      undergoing pancreaticoduodenectomy according to the American Association for the
      Surgery of Trauma-Organ Injury Scale for pancreatic and duodenal injury; and to
      validate existing indications for performance of this procedure. STUDY DESIGN: We
      performed a retrospective 126-month study (May 1992 to December 2002) of all
      patients admitted with proven complex pancreaticoduodenal injuries requiring
      pancreaticoduodenectomy. RESULTS: Eighteen patients were included; mean age was
      32 +/- 12 years (SD), mean Revised Trauma Score was 6.84 +/- 2.13 (SD), and mean
      Injury Severity Score was 27 +/- 8 (SD). There were 17 penetrating injuries (94%)
      and 1 blunt injury (6%). One of 18 patients had an emergency department
      thoracotomy and died (100% mortality); 5 of the remaining 17 patients required
      operating room thoracotomies, and only 1 survived (80% mortality). There was 1
      AAST-OIS pancreas grade IV injury, and there were 17 pancreas grade V injuries
      and 18 AAST-OIS duodenum grade V injuries. Indications for
      pancreaticoduodenectomy were: massive uncontrollable retropancreatic hemorrhage,
      13 patients (72%); massive unreconstructable injury to the head of the
      pancreas/main pancreatic duct and intrapancreatic portion/distal common bile
      duct, 18 patients (100%); and massive unreconstructable injury, 18 patients
      (100%). Mean estimated blood loss was 6,888 +/- 7,866 mL, and overall survival
      was 67% (12 of 18 patients). CONCLUSIONS: Complex pancreaticoduodenal injuries
      requiring pancreaticoduodenectomy (Whipple's procedure) are uncommon but highly
      lethal; virtually all are classified as AAST-OIS grade V for both pancreas and
      duodenum. Current indications for performance of pancreaticoduodenectomy are
      valid and should be strictly applied during procedure selection.

PMID- 14644282
TI  - Ligation of the pancreatic duct during difficult operative circumstances.
AB  - BACKGROUND: The current approach to managing the distal pancreas after
      pancreaticoduodenectomy is to anastomose the stump to either the jejunum or
      stomach, but pancreatic ductal occlusion without anastomosis of the pancreatic
      remnant remains an option during difficult operative circumstances. This article
      describes some situations in which distal pancreatic ductal ligation may be of
      use and reviews the morbidity associated with this procedure. STUDY DESIGN:
      Review was done of a prospectively kept database of operative and pathology
      reports and of both immediate and 3-month to 6-year followup data of seven
      patients who underwent ductal occlusion during pancreaticoduodenectomy or central
      pancreatectomy. RESULTS: Ductal occlusion was performed in three circumstances:
      1. necessity for expedient termination of the operation; 2. short jejunal
      mesentery allowing only a tension-free biliary or pancreatic anastomosis; and 3.
      massive jejunal edema that would result in a tenuous anastomosis. Two patients
      developed a fistula. One patient had dense residual pancreatic fibrosis, which
      resolved after 5 days; the other patient had a normal residual pancreas and
      subsequently underwent a pancreaticojejunostomy. Three patients developed acute
      pancreatitis (two had a normal and one had mild to moderate fibrosis in the
      residual pancreas) and one of these developed a peripancreatic abscess and late
      pseudocyst. Four patients with dense fibrosis did not develop acute pancreatitis.
      No patient developed either overt or worsening diabetes during the limited
      followup. None of the patients required enzyme supplementation, but all
      voluntarily maintained a low-fat diet. CONCLUSIONS: The development of
      complications after ductal ligation appears to be associated with the degree of
      fibrosis of the residual distal gland. Acute pancreatitis and fistula are the
      major complications but are associated with a low mortality. Diabetes is a
      potential late problem. The morbidity associated with ductal ligation is
      generally accepted as being greater than anastomosis, but ligation can be
      considered as an alternative in difficult circumstances where anastomosis of the
      distal pancreatic stump is believed to be unwise.

PMID- 14644283
TI  - Effects of hepatovenous back flow on ischemic- reperfusion injuries in liver
      resections with the pringle maneuver.
AB  - BACKGROUND: Experimental findings have demonstrated a beneficial role of
      retrograde blood flow from hepatic veins that takes place during the Pringle
      maneuver in liver resections. The cytoprotective effect of hepatovenous back
      perfusion has not been evaluated in humans. A randomized prospective study was
      designed to compare the response of liver cells to ischemic-reperfusion injury
      during the application of two different ischemic procedures: inflow versus inflow
      plus outflow vascular occlusion of the liver. STUDY DESIGN: Forty patients were
      randomly allocated to undergo liver resection using the continuous Pringle
      maneuver (n = 20) or inflow plus outflow vascular occlusion of the liver by
      selective hepatic vascular exclusion (n = 20). Liver function was assessed on
      postoperative days 1 to 6. Response of liver cells to I/R injury was evaluated by
      measuring interleukins IL-6 and IL-8 at 3, 12, 24, and 48 hours after
      reperfusion. Oxidative stress was assessed by measuring malondialdehyde levels.
      RESULTS: Both groups were comparable regarding ischemic time, operative time, and
      extent of liver resection. Patients in whom retrograde blood flow to the liver
      took place during the Pringle maneuver showed better liver function
      postoperatively and less severe hepatic I/R injuries compared with those
      undergoing liver resection using both inflow and outflow vascular occlusion.
      Oxidative stress was significantly lower in the Pringle maneuver group compared
      with the inflow plus outflow vascular occlusion group (mean [+/- SD]
      malondialdehyde 8 +/- 2.1 micromol/L in the Pringle group versus 14.7 +/- 1.8
      micromol/L in the selective hepatic vascular exclusion group 30 min after
      reperfusion, p < 0.01). CONCLUSIONS: Back perfusion via hepatic veins contributes
      to attenuation of I/R damage during the Pringle maneuver and should be preferred
      if possible during liver resection.

PMID- 14644284
TI  - Results of interval debulking surgery compared with primary debulking surgery in
      advanced stage ovarian cancer.
AB  - BACKGROUND: Results of IDS (after three to four courses of induction
      chemotherapy) were compared with PDS followed by chemotherapy in patients treated
      for advanced stage ovarian cancer (stage IIIC or IV). STUDY DESIGN: A
      retrospective study was done on a group of 57 patients who underwent IDS (because
      of an unresectable tumor) compared with a group of 28 patients treated with PDS
      (for resectable disease) followed by chemotherapy. All patients were treated
      between 1996 and 2001 by the same team of surgeons and received the same regimen
      of chemotherapy (platinum based plus paclitaxel). RESULTS: Optimal cytoreductive
      surgery (residual disease < or = 2 cm) was achieved in IDS and PDS groups in 84%
      (48 of 57) and 100% (28 of 28) of patients, respectively. Complete resection was
      observed in 51% (29 of 57) of patients in the IDS group and 54% (15 of 28) of
      patients in the PDS group. The rates of bowel resection, large peritoneal
      resection, and postoperative morbidity were significantly reduced in the IDS
      group. After adjusting for the size of residual disease (< or /= 2 cm and absence
      of residual tumor), overall and event-free survival were not different in the two
      groups. CONCLUSIONS: Survival rates were similar in patients with advanced stage
      ovarian cancer who underwent IDS or PDS. The rates of surgical resection and
      morbidity were reduced after IDS. IDS can be safely used in unresectable advanced
      stage ovarian cancer.

PMID- 14644285
TI  - Mcl-1 correlates with reduced apoptosis in neutrophils from patients with sepsis.
AB  - BACKGROUND: Reduction of PMN apoptosis during sepsis contributes to the
      pathogenesis of multiple organ failure. Differential expression of Bcl-2
      proteins, which participate in apoptosis regulation, may be responsible for the
      dysbalanced apoptosis seen in neutrophils from septic patients. In this study,
      expression of Mcl-1, Bid, Bcl-2, and Bax were investigated in septic neutrophils.
      STUDY DESIGN: PMN (1 x 10(6)/mL) from septic patients (n = 16) or healthy
      volunteers (n = 10) were incubated with either lipopolysaccharide (1 microg/mL),
      agonistic CD95 antibody (100 ng/mL), or medium for 16 hours. Apoptosis was
      quantified in FACS after propidium iodine staining. Mcl-1, Bid, Bcl-2, and Bax
      mRNA expression was detected by reverse transcriptase-polymerase chain reaction
      and protein determined by Western blot analysis. RESULTS: Spontaneous apoptosis
      was significantly reduced in PMN from septic patients (28.8% versus 64.0% in
      controls). Mcl-1 protein levels decreased in patients after 16 hours but remained
      stable in controls. Mcl-1 mRNA was found in freshly isolated PMN from controls
      and patients but remained elevated only in patients. Bid protein level decreased
      significantly in control PMN undergoing apoptosis but differences were less
      prominent in septic patients. Bid mRNA was detected only in freshly isolated PMN.
      No Bcl-2 mRNA or protein was detected in neutrophils from patients or controls,
      and detectable Bax protein and mRNA levels remained unchanged in all samples.
      CONCLUSIONS: Alterations of Bid and Mcl-1 protein in neutrophils may reflect the
      level of apoptosis. The upregulation of Mcl-1 mRNA in patients with sepsis
      suggests an active role for Mcl-1 in regulation of apoptosis during sepsis; Bax
      remains unchanged.

PMID- 14644286
TI  - Bile salts regulate intestinal epithelial cell migration by nuclear factor-kappa
      B-induced expression of transforming growth factor-beta.
AB  - BACKGROUND: Mucosal restitution is an important repair modality in the
      gastrointestinal tract. We have shown that taurodeoxycholate increases intestinal
      epithelial cell migration by increasing TGF-beta expression, and that the
      transcription factor NF-kappa B regulates TDCA induced cell migration after
      injury. The objectives of this study were to determine if this is a property
      shared by other bile salts or an effect specific to TDCA, and to determine if NF
      kappa B regulates TGF-beta expression. STUDY DESIGN: Studies were conducted in
      IEC-6 cells. Cell migration was examined using an in vitro model. TGF-beta
      protein and mRNA expression was determined by ELISA and Northern blot analysis.
      Sequence-specific NF-kappa B binding activity was measured by gel shift assays.
      RESULTS: Taurocholate and deoxycholate at physiologic concentrations
      significantly increased intestinal epithelial cell migration 6 hours after
      wounding (p < 0.01), and was associated with a significant increase in specific
      NF-kappa B binding activity. Inhibition of NF-kappa B activity significantly
      inhibited cell migration during restitution and resulted in a significant
      decrease in TGF-beta mRNA expression and protein expression. CONCLUSIONS: We
      conclude that bile salts at physiologic conditions increase cell migration after
      injury, an effect regulated by NF-kappa B. Further, NF-kappa B elicits TGF-beta
      gene transcription during cell migration. These data support a physiologic role
      of bile salts in the maintenance of intestinal mucosal integrity.

PMID- 14644287
TI  - What's new in orthopaedic surgery.

PMID- 14644288
TI  - Shortterm and longterm visual and astigmatic results of an opposing 10-0 nylon
      double running suture technique for penetrating keratoplasty.
AB  - BACKGROUND: In ophthalmic surgery, corneal transplantation (penetrating
      keratoplasty) may be employed when the clarity of the cornea has been
      significantly compromised by conditions such as scarring, edema, and variable
      corneal thickness. Irregularities in corneal curvature can occur postoperatively.
      This astigmatism is of concern, because it can impair visual acuity despite an
      otherwise good surgical result. Different suturing techniques have been developed
      to minimize astigmatism. The purpose of this study was to evaluate an opposing 10
      0 nylon double running suture technique for penetrating keratoplasty. STUDY
      DESIGN: A retrospective study was undertaken of 91 records of patients who
      underwent penetrating keratoplasty performed by one surgeon (RNG). This
      represents 54.8% of 166 consecutive cases. Every eye with an opposing double
      running suture and a 1- to 3-month postsuture removal followup was selected and
      evaluated for best corrected visual acuity and astigmatism, excluding eyes that
      developed graft failure or corneal ulcer or that had lack of adequate followup.
      The cases were divided into five groups by preoperative diagnosis: pseudophakic
      bullous keratopathy (n = 43), aphakic bullous keratopathy (n = 5), keratoconus (n
      = 17), Fuchs dystrophy (n = 12), and miscellaneous (n = 14). The mean standard
      followup period was 13.7 months after penetrating keratoplasty. Thirty percent of
      the eyes had an extensive followup, with a mean of 33 months after penetrating
      keratoplasty. RESULTS: Eighty-two percent of the patients had a significant
      improvement of their visual acuity postoperatively, defined by a five-line
      improvement of best corrected visual acuity or a best corrected visual acuity of
      20/40 or better. The mean astigmatic keratometric reading was 3.98 diopters, with
      a manifest refraction cylinder of 3.42 diopters at the 1- to 3-month postsuture
      removal visit. This study also shows that there is no statistically significant
      change in keratometric astigmatism or manifest refraction cylinder from the 1- to
      3-month postsuture removal measurements to the more extensive followup of 18 to
      66 months after penetrating keratoplasty (p > 0.10). CONCLUSIONS: This suture
      technique allows for excellent longterm stability of the wound with visual and
      astigmatic results that are comparable to those of previous studies. The use of
      the opposing double running suture is a viable alternative to some of the other
      widely used techniques and may be considered more stable and secure.

PMID- 14644289
TI  - Comparison of private versus academic practice for general surgeons: a guide for
      medical students and residents.
AB  - BACKGROUND: Medical students and residents often make specialty and practice
      choices with limited exposure to aspects of professional and personal life in
      general surgery. The purpose of this study was to portray practice composition,
      career choices, professional experiences, job satisfaction, and personal life
      characteristics specific to practicing general surgeons in the United States.
      STUDY DESIGN: A 131-question survey was mailed to all female members (n = 1,076)
      and a random 2:1 sample of male members (n = 2,152) of the American College of
      Surgeons in three mailings between September 1998 and March 1999. Respondents who
      were not actively practicing general surgery in the United States and both
      trainees and surgeons who did not fit the definition of private or academic
      practice were excluded. Detailed questions regarding practice attributes,
      surgical training, professional choices, harassment, malpractice, career
      satisfaction, and personal life characteristics were included. Separate five
      point Likert scales were designed to measure influences on career choices and
      satisfaction with professional and personal matters. Univariate analyses were
      used to analyze responses by surgeon age, gender, and practice type. RESULTS: A
      response rate of 57% resulted in 1,532 eligible responses. Significant
      differences between private and academic practice were noted in case composition,
      practice structure, and income potential; no major differences were seen in
      malpractice experience. Propensity for marriage and parenthood differed
      significantly between men and women surgeons. Overall career satisfaction was
      very high regardless of practice type. Some differences by surgeon gender in
      perceptions of equal career advancement opportunities and of professional
      isolation were noted. CONCLUSIONS: This study offers a comprehensive view of
      general surgery to enable more informed decisions among medical students and
      residents regarding specialty choice or practice opportunities.

PMID- 14644290
TI  - "And doctor, no residents please!".

PMID- 14644291
TI  - A comparison of antifibrinolytic agents used in hemostatic fibrin sealants.

PMID- 14644292
TI  - Available models for breast cancer risk assessment: how accurate are they?

PMID- 14644293
TI  - Massage as adjuvant therapy in the management of acute postoperative pain: a
      preliminary study in men.
AB  - BACKGROUND: Opioid analgesia alone may not fully relieve all aspects of acute
      postoperative pain. Complementary medicine techniques used as adjuvant therapies
      have the potential to improve pain management and palliate postoperative
      distress. STUDY DESIGN: This prospective randomized clinical trial compared pain
      relief after major operations in 202 patients who received one of three nursing
      interventions: massage, focused attention, or routine care. Interventions were
      performed twice daily starting 24 hours after the operation through postoperative
      day 7. Perceived pain was measured each morning. RESULTS: The rate of decline in
      the unpleasantness of postoperative pain was accelerated by massage (p = 0.05).
      Massage also accelerated the rate of decline in the intensity of postoperative
      pain but this effect was not statistically significant. Use of opioid analgesics
      was not altered significantly by the interventions. CONCLUSIONS: Massage may be a
      useful adjuvant therapy for the management of acute postoperative pain. Its
      greatest effect appears to be on the affective component (ie, unpleasantness) of
      the pain.

PMID- 14644294
TI  - Splenic volvulus.

PMID- 14644295
TI  - Reversed rotation of the midgut presenting as duodenal and transverse colon
      obstruction in a 19-year-old man.

PMID- 14644296
TI  - An innovative approach for repair of complex inguinal and abdominal wall hernias.

PMID- 14644297
TI  - Loop-configured upper-arm hemodialysis graft for the "hostile" arm.

PMID- 14644298
TI  - Left portahepatic shunt: a novel technique to decrease excessive portal venous
      inflow during live donor liver transplantation.

PMID- 14644301
TI  - Filling the gaps in physician communication. The role of the Internet among
      primary care patients.
AB  - BACKGROUND: Millions of people use the Internet as a source for health
      information yet little is understood about how the use of the Internet for health
      information is related to the doctor-patient relationship. OBJECTIVE: We
      conducted the present study to understand the association between one's interest
      in using the Internet for general and quality-oriented health information and
      attitudes about one's communications with health care provider(s). DESIGN: Cross
      sectional survey. SETTING: Four community-based primary care practices in Rhode
      Island. MEASUREMENTS: A single self-administered survey included items to
      measure: interest in using the Internet to look for general and quality-oriented
      information and a patient's perceptions of the degree to which their doctors over
      the previous year have: (1) given them information and (2) engaged them in the
      decision-making process. RESULTS: A total of 300 patients completed the survey.
      Among patients without Internet access, interest in using the Internet for health
      related activities was less among patients who felt that their doctor gave less
      information: Odds ratio 0.83 (95% CI, 0.70-0.98) and greater among patients who
      felt that their doctor engaged them more in decision making: Odds ratio 1.3 (95%
      CI, 1.1-1.6). Among patients with Internet access, we found no relationship
      between interest in using the Internet for health related activities and measures
      of patient-physician communication or patient-physician decision making.
      CONCLUSIONS: Interest in using the Internet for health information is greater for
      those who (1) felt their doctors provided less information and (2) felt their
      doctors engaged them more in the decision-making process, but this is true only
      for those without access to the Internet.

PMID- 14644302
TI  - Does failure breed success: narrative analysis of stories about computerized
      provider order entry.
AB  - OBJECTIVE: To assess the definitions of success and failure as defined by the
      participants of the Menucha Consensus Conference on Computerized Provider Order
      Entry (CPOE). DESIGN: Thirteen experts from various fields participated in
      Menucha Consensus Conference. Though they belonged to different fields, all of
      them had some kind of experience in CPOE implementation. MEASUREMENTS: The
      stories of these experts were analyzed using a constant comparison method and
      partially ordered display. RESULTS: Each participant told a success and a failure
      story. Definitions of success and failure, as well as variables contributing to
      the success and failure of CPOE implementations, were extracted from the
      transcripts. CONCLUSION: Analysis reveals that what is considered a failure is
      context dependent and that it often is an antecedent to success.

PMID- 14644303
TI  - Automated coded ambulatory problem lists: evaluation of a vocabulary and a data
      entry tool.
AB  - BACKGROUND: Problem lists are fundamental to electronic medical records (EMRs).
      However, obtaining an appropriate problem list dictionary is difficult, and
      getting users to code their problems at the time of data entry can be
      challenging. OBJECTIVE: To develop a problem list dictionary and search algorithm
      for an EMR system and evaluate its use. METHODS: We developed a problem list
      dictionary and lookup tool and implemented it in several EMR systems. A sample of
      10,000 problem entries was reviewed from each system to assess overall coding
      rates. We also performed a manual review of a subset of entries to determine the
      appropriateness of coded entries, and to assess the reasons other entries were
      left uncoded. RESULTS: The overall coding rate varied significantly between
      different EMR implementations (63-79%). Coded entries were virtually always
      appropriate (99%). The most frequent reasons for uncoded entries were due to user
      interface failures (44-45%), insufficient dictionary coverage (20-32%), and non
      problem entries (10-12%). CONCLUSION: The problem list dictionary and search
      algorithm has achieved a good coding rate, but the rate is dependent on the
      specific user interface implementation. Problem coding is essential for providing
      clinical decision support, and improving usability should result in better coding
      rates.

PMID- 14644304
TI  - An investigation into low mail survey response rates of information technology
      users in health care organizations.
AB  - Surveys conducted by mail can result in a very low response rate raising the
      possibility of non-response bias that would question the validity of the
      findings. In this study, we compare the demographic profiles between the
      respondents and non-respondents, and conduct wave analysis as an alternative way
      to estimate the non-response bias among the information technology (IT) users in
      the health care industry. Our findings indicate that there is no significant
      difference among the respondents when considering the duration (early versus
      late) of response rate. Likewise, there was no significant difference when the
      available demographic characteristics (facility type and user's position) of
      those who responded were compared to the same characteristics of the sample. We
      were able to reach similar conclusion by using either of the proposed methods;
      analysis of demographic profiles of respondents versus non-respondents, and wave
      analysis. Thus our findings support the validity of the results from low response
      mail survey studies for IT users.

PMID- 14644305
TI  - Criteria of interface evaluation for computer assisted surgery systems.
AB  - OBJECTIVES: The evaluation of computer assisted surgery (CAS) systems in terms of
      clinical outcomes and ergonomic features is more and more relevant. The goal of
      this paper is to provide criteria to define effective evaluation protocols of HCI
      for CAS systems. METHOD: The proposed criteria include the use of two
      questionnaires prepared by the authors, aimed at analyzing the subjective feeling
      of the surgeons in using the system's tools, and objective aspects of the system.
      These questionnaire have to be submitted to system's end-users and to experts in
      HCI development iteratively during the system development or once at the end. A
      quantitative evaluation of the main parameters related to the surgical
      application is also required as an index of system efficacy. The demonstration
      application was planning software developed for the total knee replacement (TKR).
      RESULTS AND CONCLUSIONS: In our TKR planning software the proposed evaluation
      procedure provided useful indications about the efficacy of HCI and also about
      further developments of its design and functionality. Moreover, since surgical
      training systems and surgical navigation platforms also share data treatment and
      layout similar to the presented TKR planner, these kinds of applications can
      benefit directly from the proposed approach to HCI design and evaluation.

PMID- 14644306
TI  - A model for interpreting work and information management in process-oriented
      healthcare organisations.
AB  - BACKGROUND: To increase productivity, management in healthcare organisations have
      introduced different types of process-oriented organisational configurations. Few
      studies have addressed clinical practice and information management in these
      settings. METHODS: A case study was performed at a paediatric clinic. Data was
      collected from archives, through interviews, by participatory observation, and by
      performing a focus group session. The collected data was analysed using a
      qualitative and interpretative research strategy. RESULTS: A model was developed
      of care practitioners' daily work in process-oriented organisations. The model
      shows that clinical work was deeply integrated; the care activities were
      dependent on supply activities and tightly connected to management routines.
      CONCLUSION: The resulting model can be used to support development of health
      information system (HIS) embedded in process-oriented healthcare work.

PMID- 14644307
TI  - Modeling an emergency medical services system using computer simulation.
AB  - STUDY OBJECTIVES: In the emergency medical services (EMS) system, appropriate
      prehospital care can substantially decrease casualty mortality and morbidity.
      This study designed a simulation model, evaluated the existing EMS system, and
      suggested improvements. METHODS: The study focused on 23 networked EMS hospitals
      affiliated with 36 emergency response units (subgroups) to perform two-tier
      rescues (advanced life support [ALS] in addition to basic life support [BLS]
      services) in Taipei, Taiwan. Using the existing EMS model as a base, this
      research constructed a computer simulation model and explored several model
      alternatives to achieve the study's objectives. The virtual models varied with
      staffing level, number of assigned emergency network hospitals, and various two
      tier rescue probabilities. RESULTS: Increasing the staffing to two teams for
      Hospital 22 lessened the call waiting probability (delay between rescue call and
      ambulance dispatch) by 50%, even if the dispatch rate of the two-tier rescue
      increased from the empirical 2% to a simulated 10 and 20%. Changing the two-tier
      rescue pattern so each EMS subgroup cooperated with two specific, preassigned
      network hospitals lowered the probability of patients having to wait for rescue
      dispatch to under 1%. CONCLUSION: The following alternatives provided the
      greatest combination of effectiveness, quality patient care, and cost-efficiency:
      (1) because of its unique location, increase Hospital 22's staffing level to two
      ALS teams. (2) Establish a specific rescue protocol for the two-tier system that
      preassigns two network hospitals to each of the 36 EMS subgroups along with a
      prearranged calling sequence. If implemented, this will improve EMS performance,
      streamline the system, reduce randomness, and enhance efficiency.

PMID- 14644308
TI  - A real time collaboration system for teleradiology consultation.
AB  - Real time collaboration systems, in which participants share multimedia data and
      applications in real time, have attracted many researchers in recent years. A
      teleradiology consultation system based on the real time collaboration technology
      is presented in this paper. Under the platform-independence consideration, Java
      technologies are employed to construct the system. Applying this system, an off
      duty on-call radiologist can make diagnoses and report easily by viewing the
      transferred images at home. Owing to the accessibility of image, all users can
      examine and manipulate images consistently such that a secluded hospital can be
      assisted to hold remote consultation. To reduce the network transmission time,
      the command-passing and local command execution techniques are utilized to
      achieve the screen synchronization. A pointer function is also developed to
      maintain the cursor consistency in a more efficient manner during consultation
      when a detail indication of the examined image is needed. Besides, a dialog
      window is also designed for on-line conversation. Since Java programs can run on
      heterogeneous platforms, the need for system maintenance and user training can be
      substantially reduced.

PMID- 14644311
TI  - International conferences on environmental mutagens in human populations
      opportunities, accomplishments and challenges.
AB  - A major mission for organizing the series of International Conferences on
      Environmental Mutagens in Human Populations is to bring science and scientists to
      the sites where the field of environmental health is in developmental stages and
      environmental health is a serious concern. The mission has been fulfilled in each
      of the previous conferences that were held in Egypt, Czech Republic, Thailand and
      Brazil. These conferences have led to significant enhancement of regional
      scientific expertise from the acquisition of scientific knowledge and from the
      generation of sustainable collaborative programs.

PMID- 14644312
TI  - An overview of the mechanisms of mutagenesis and carcinogenesis.
AB  - Cancer is a genetic disease due to the accumulation of numerous mutations
      rendering the tumour cell insensitive to control by the local cellular
      environment and by the whole organism. Analysis of the frequency of appearance of
      human cancer as a function of age shows that between four and seven mutations in
      key genes are usually necessary to produce most human cancers. Interesting
      debates in the literature are concerned with the idea that normal mutation rates
      followed by selective advantage of mutated clones are enough to produce the
      numerous mutations found in human cancers. Alternatively, the mutator phenotype
      hypothesis is based on the idea that the normal mutation rates are insufficient
      to account for the multiple mutations found in tumours. It is, however, difficult
      not only to know this exact mutation frequency in cells but also to know the
      total number of cell divisions giving rise to a cancer. Therefore, during at
      least one step in the carcinogenic process, a mutator phenotype in target cells
      may occur due to mutations controlling the fidelity of DNA replication or DNA
      repair, the apoptosis pathways or the cell cycle checkpoint regulations. Among
      the multiple mutations found in human cancers such as gene amplification,
      chromosome alterations and translocations, point mutations are very important and
      the molecular mechanisms of their production are well documented. I will describe
      in detail the various mechanisms that a cell can use to produce point mutations
      due to lower fidelity in the DNA polymerisation step or to inefficient repair
      pathways. The presence of multiple mutations in human cancer is interesting not
      only in terms of understanding the carcinogenesis process in humans but also in
      eventually promoting strategies to decrease the efficiency of this process and to
      increase cancer therapy regimen.

PMID- 14644313
TI  - Functional characterization of global genomic DNA repair and its implications for
      cancer.
AB  - The most versatile cellular pathway for dealing with a large variety of
      structurally-unrelated DNA alterations is nucleotide excision repair (NER). Most
      genomic damage, if not repaired, may contribute to mutagenesis and
      carcinogenesis, as well as to cellular lethality. There are two subpathways of
      NER, termed global genomic repair (GGR) and transcription-coupled repair (TCR);
      While GGR deals with all repairable lesions throughout the genome, TCR is
      selective for the transcribed DNA strand in expressed genes. Proteins involved in
      the initial recognition of lesions for GGR as well as for TCR (i.e. RNA
      polymerase) may sometimes initiate gratuitous repair events in undamaged DNA.
      However, the damage recognition enzymes for GGR are normally maintained at very
      low levels unless the cells are genomically stressed. Following UV irradiation in
      human fibroblasts the efficiency of GGR is upregulated through activation of the
      p53 tumor suppressor gene. The transactivation role of p53 includes control of
      expression of the genes, XPC and XPE, which are implicated in GGR but not TCR.
      These inducible responses are essential for the efficient repair of the most
      prominent lesion produced by UV, the cyclobutane pyrimidine dimer (CPD). They are
      also clinically relevant, as we have shown them to operate upon chemical
      carcinogen DNA damage at levels to which humans are environmentally exposed (e.g.
      through smoking). Thus, for benzo(a)pyrene (at 10-50 adducts per 10(8)
      nucleotides) repair was essentially complete within 1 day in p53(+/+) human
      fibroblasts while no repair was detected within 3 days in p53(-/-) cells. The
      levels of all four DNA adducts formed by benzo(g)chrysene, also exhibited p53
      dependent control in human fibroblasts. However, unlike humans most rodent
      tissues are deficient in the p53-dependent GGR pathway. Since rodents are used as
      surrogates for humans in environmental cancer risk assessment it is very
      important that we determine how they differ from humans with respect to DNA
      repair and oncogenic responses to environmental genotoxins.

PMID- 14644314
TI  - Oxidative and alkylating damage in DNA.
AB  - Modification of cellular DNA upon exposure to reactive oxygen and nitrogen
      species is the likely initial event involved in the induction of the mutagenic
      and lethal effects of various oxidative stress agents. Evidence has been
      accumulated for the significant implication of singlet oxygen (1O(2)), generated
      as the result of UVA activation of endogenous photosensitizers as porphyrins and
      flavins. 7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo) has been shown to be the
      exclusive product of the reaction of 1O(2) with the guanine moiety of cellular
      DNA, in contrast to the hydroxyl radical, which reacts almost indifferently with
      all the nucleobases and the sugar moiety of DNA. Furthermore 8-oxodGuo is also
      produced by other oxidants and can be used as an ubiquitous biomarker of DNA
      oxidation but can not be a specific marker of any particular species. The role of
      DNA etheno adducts in mutagenic and carcinogenic processes triggered by known
      occupational and environmental carcinogens has also been studied. Much interest
      in etheno adducts resulted from the detection of increased levels of 1,N(6)
      etheno-2'-deoxyadenosine and 3,N(4)-etheno-2'-deoxycytidine in DNA from human,
      rat and mouse tissues under pathophysiological conditions associated with
      oxidative stress. A method involving on-line HPLC with electrospray tandem mass
      spectrometry detection has been developed for the analysis of 1,N(2)-etheno-2'
      deoxyguanosine (1,N(2)-epsilondGuo) in DNA. This methodology permits direct
      quantification of 20 fmol (7.4 adducts/10(8) dGuo) of the etheno adduct from
      approximately 350 microg of crude DNA hydrolysates. This method provides the
      first evidence of the occurrence of 1,N(2)-epsilondGuo as a basal endogenous
      lesion and may be utilized to better assess the biological consequences of etheno
      DNA damage under normal and pathological conditions. This work addresses the
      importance of isotope labeling associated with mass spectrometry technique for
      biomolecule damage studies.

PMID- 14644315
TI  - Oxidative DNA damage and glioma cell death induced by tetrahydropapaveroline.
AB  - A series of naturally occurring isoquinoline alkaloids, besides their
      distribution in the environment and presence in certain food stuffs, have been
      detected in human tissues including particular regions of brain. An example is
      salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) that not only
      induces neuronal cell death, but also causes DNA damage and genotoxicity.
      Tetrahydropapaveroline [THP; 6,7-dihydroxy-1-(3',4'-dihydroxybenzyl)-1,2,3,4
      tetrahydroisoquinoline], a dopamine-derived tetrahydroisoquinoline alkaloid, has
      been reported to inhibit mitochondrial respiration and is considered to
      contribute to neurodegeneration implicated in Parkinson's disease. Since THP
      bears two catechol moieties, the compound may readily undergo redox cycling to
      produce reactive oxygen species (ROS) as well as toxic quinoids. In the present
      study, we have examined the capability of THP to cause oxidative DNA damage and
      cell death. Incubation of THP with phiX174 supercoiled DNA or calf thymus DNA in
      the presence of cupric ion caused substantial DNA damage as determined by strand
      scission or formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo),
      respectively. THP plus copper-induced DNA damage was ameliorated by some ROS
      scavengers/antioxidants and catalase. Treatment of C6 glioma cells with THP led
      to a concentration-dependent reduction in cell viability, which was prevented by
      the antioxidant N-acetyl-L-cysteine. When these cells were treated with 10microM
      THP, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase
      (MAPK) were rapidly activated via phosphorylation, whereas activation of
      extracellular signal-regulated protein kinase (ERK) was inhibited. Furthermore,
      pretreatment with inhibitors of JNK and p38 MAPK rescued the glioma cells from
      THP-induced cytotoxicity, suggestive of the involvement of these kinases in THP
      induced C6 glioma cell damage.

PMID- 14644316
TI  - New insights on how nucleotide excision repair could remove DNA adducts induced
      by chemotherapeutic agents and psoralens plus UV-A (PUVA) in Escherichia coli
      cells.
AB  - Chemotherapeutic agents such as mitomycin C or nitrogen mustards induce DNA inter
      strand cross-links (ICL) and are highly toxic, thus constituting an useful tool
      to treat some human degenerative diseases, such as cancer. Additionally,
      psoralens plus UV-A (PUVA), which also induce ICL, find use in treatment of
      patients afflicted with psoriasis and vitiligo. The repair of DNA ICL generated
      by different molecules involves a number of multi-step DNA repair pathways. In
      bacteria, as in eukaryotic cells, if DNA ICL are not tolerated or repaired via
      nucleotide excision repair (NER), homologous recombination or translesion
      synthesis pathways, these DNA lesions may lead to mutations and cell death.
      Herein, we bring new insights to the role of Escherichia coli nucleotide excision
      repair genes uvrA, uvrB and uvrC in the repair of DNA damage induced by some
      chemotherapeutic agents and psoralen derivatives plus UV-A. These new
      observations point to a novel role for the UvrB protein, independent of its
      previously described role in the Uvr(A)BC complex, which could be specific for
      repair of monoadducts, intra-strand biadducts and/or ICL.

PMID- 14644317
TI  - Effect of cell confluence on ultraviolet light apoptotic responses in DNA repair
      deficient cells.
AB  - One of the major critical factors for cancer proneness is the cell response to
      DNA damage. In this work, we used human DNA repair deficient cell lines to
      investigate the responses to ultraviolet irradiation that lead to apoptosis, and
      the influence of maintaining the cells resting in confluent state. UV-induced
      apoptosis is prevented in photolyase-proficient HeLa cells when cyclobutane
      pyrimidine dimers (CPDs) are removed by photorepair. At the same time, we show
      recovery of RNA synthesis, thus indicating that blockage of RNA transcription may
      trigger apoptosis in human cells. On the other hand, confluent primary XPC and
      trichothiodystrophy (TTD)/XPD cell lines, related to xeroderma pigmentosum and
      trichothiodystrophy repair syndromes, had a reduced and delayed apoptosis when
      compared to non-confluent cells. In contrast, XPA cells were similarly sensitive
      in both the confluent and non-confluent growing state. The effect of cellular
      confluence on UV-mediated apoptosis in CSB cells, related to Cockayne's syndrome,
      was unclear. Thus, these results indicate that the induction of apoptosis by UV
      light may also be affected by DNA replication. In addition, they argue for the
      use of confluent primary cells in studies of induction of apoptosis by UV, a
      condition close to skin cells in vivo.

PMID- 14644318
TI  - Apoptosis induced by MNNG in human TK6 lymphoblastoid cells is p53 and
      Fas/CD95/Apo-1 related.
AB  - Agents inducing O(6)-methylguanine (O(6)MeG) in DNA, such as N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), are not only highly mutagenic and carcinogenic but also
      cytotoxic because of the induction of apoptosis. In CHO fibroblasts, apoptosis
      triggered by O(6)MeG requires cell proliferation and MutSalpha-dependent mismatch
      repair and is related to the induction of DNA double-strand breaks (DSBs).
      Furthermore, it is mediated by Bcl-2 degradation and does not require p53 for
      which the cells were mutated [Cancer Res. 60 (2000) 5815]. Here we studied
      cytotoxicity and apoptosis induced by MNNG in a pair of human lymphoblastoid
      cells expressing wild-type p53 (TK6) and mutant p53 (WTK1) and show that TK6
      cells are more sensitive than WTK1 cells to cell killing (determined by a
      metabolic assay) and apoptosis. Apoptosis was a late response observed <24h after
      treatment and was related to accumulation of p53 and upregulation of Fas/CD95/Apo
      1 receptor as well as Bax. The data indicate that MNNG induces apoptosis in
      lymphoblastoid cells by activating the p53-dependent Fas receptor-driven pathway.
      This is in contrast to CHO fibroblasts in which, in response to O(6)MeG, the
      mitochondrial damage pathway becomes activated.

PMID- 14644319
TI  - Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the
      Comet assay).
AB  - Reactive oxygen species (ROS) are produced by a wide variety of chemicals and
      physiological processes in which enzymes catalyse the transfer of electrons from
      a substrate to molecular oxygen. The immediate products of such reactions,
      superoxide anion radicals and hydrogen peroxide can be metabolised by enzymes
      such as superoxide dismutase (SOD) and catalase (CAT), respectively, and
      depending on its concentration by Vitamin C (Vit C). Under certain circumstances
      the ROS form highly reactive hydroxyl radicals. We examined human sperm and
      lymphocytes after treatment with six oestrogenic compounds in the Comet assay,
      which measures DNA damage, and observed that all caused damage in both cell
      types. The damage was diminished in nearly all cases by catalase, and in some
      instances by SOD and Vit C. This response pattern was also seen with hydrogen
      peroxide. This similarity suggests that the oestrogen-mediated effects could be
      acting via the production of hydrogen peroxide since catalase always markedly
      reduced the response. The variable responses with SOD indicate a lesser
      involvement of superoxide anion radicals due to SOD-mediated conversion of
      superoxide to hydrogen peroxide generally causing a lower level of DNA damage
      than other ROS. The variable Vit C responses are explained by a reduction of
      hydrogen peroxide at low Vit C concentrations and a pro-oxidant activity at
      higher concentrations. Together these data provide evidence that inappropriate
      exposure to oestrogenic compounds could lead to free-radical mediated damage. It
      is believed that the observed activities were not generated by cell free cell
      culture conditions because increased responses were observed over and above
      control values when the compounds were added, and also increasing dose-response
      relationships have been found after treatment with such oestrogenic compounds in
      previously reported studies.

PMID- 14644320
TI  - Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae.
AB  - Photoactivated psoralens used in treatment of skin diseases like Psoriasis and
      Vitiligo cause DNA damage, the repair of which may lead to mutations and thus to
      higher risk to have skin cancer. The simple eukaryote Saccharomyces cerevisiae
      was chosen to investigate the cells' genetic endowment with repair mechanisms for
      this type of DNA damage and to study the genetic consequences of such repair.
      Genetic studies on yeast mutants sensitive to photoactivated psoralens, named pso
      mutants, showed their allocation to 10 distinct loci. Cloning and molecular
      characterization allowed their grouping into three functional classes: (I) the
      largest group comprises seven PSO genes that are either generally or specifically
      involved in error-prone DNA repair and thus affect induced mutability and
      recombination; (II) one PSO gene that represents error-free excision repair, and
      (III) two PSO genes encoding proteins not influencing DNA repair but
      physiological processes unrelated to nucleic acid metabolism. Of the seven DNA
      repair genes involved in induced mutagenesis three PSO loci [PSO1/REV3,
      PSO8/RAD6, PSO9/MEC3] were allelic to already known repair genes, whereas three,
      PSO2/SNM1, PSO3/RNR4, and PSO4/PRP19 represent new genes involved in DNA repair
      and nucleic acid metabolism in S. cerevisiae. Gene PSO2 encodes a protein
      indispensable for repair of interstrand cross-link (ICL) that are produced in DNA
      by a variety of bi- and polyfunctional mutagens and that appears to be important
      for a likewise repair function in humans as well. In silico analysis predicts a
      putative endonucleolytic activity for Pso2p/Snm1p in removing hairpins generated
      as repair intermediates. The absence of induced mutation in pso3/rnr4 mutants
      indicates an important role of this subunit of ribonucleotide reductase (RNR) in
      regulation of translesion polymerase zeta in error-prone repair. Prp19p/Pso4p
      influences efficiency of DNA repair via splicing of pre-mRNAs of intron
      containing repair genes but also may function in the stability of the nuclear
      scaffold that might influence DNA repair capacity. The seventh gene, PSO10 which
      controls an unknown step in induced mutagenesis is not yet cloned. Two genes,
      PSO6/ERG3 and PSO7/COX11, are responsible for structural elements of the membrane
      and for a functional respiratory chain (RC), respectively, and their function
      thus indirectly influences sensitivity to photoactivated psoralens.

PMID- 14644321
TI  - Dietary components may prevent mutation-related diseases in humans.
AB  - Since it is not always possible to reduce human exposure to mutagens, attempts
      have been directed to identify potential antimutagens and anticarcinogens for use
      in protecting the population against environmental disease. The purpose of this
      paper is to provide the reader with information about the antimutagenic and
      anticarcinogenic potentials of some dietary constituents and foods widely
      consumed in Brazil, and to reinforce diet as a key factor in determining genomic
      stability and preventing human diseases. In this report, we have summarized data
      that show interactive effects between some dietary components and specific
      chemical mutagens or carcinogens using in vitro and in vivo short- or medium-term
      assays. The summary indicates that certain dietary compounds may be useful agents
      for disease prevention.

PMID- 14644322
TI  - Neuroprotection by bioactive components in medicinal and food plant extracts.
AB  - Neurodegenerative diseases of the human brain comprise a variety of disorders
      that affect an increasing percentage of the population. Some of these are age
      dependent (e.g. Alzheimer's and Parkinson's diseases) and some are infection
      dependent, e.g. human immunodeficiency virus (HIV/AIDS). The vulnerable brain
      regions in HIV/AIDS individuals include the dentate nucleus in the cerebellum,
      the red nucleus, substantia nigra (SN) in the mid-brain, the subthalamic nucleus,
      thalamic fasciculus in the diencephalons, the globus pallidus and striatum (or
      neostriatum, which consists of caudate and putamen) in the forebrain. Lesion in
      these regions may lead to progressive dementia, which is similar to what is
      observed in Alzheimer's disease and Parkinson's disease. The entry of calcium
      into the cytoplasm of cells at concentrations that can activate oxidative enzymes
      such as phospholipase A(2) and xanthine oxidase, deplete cells of cysteine and
      glutathione, cause mitochondrial release of free radicals and cell death.
      Glutamate and its receptors are key molecular elements at the interface between
      neurons and glia. Dietary factors can modulate physiological functions (including
      brain function) thereby increasing the economic productivity of a population as a
      function of health. A greater understanding of the molecular mechanisms of
      neuroprotection, oxidative stress and immune function will facilitate definition
      of the prophylactic potentials of diet, nutritional/food supplements, medicinal
      plants and herbal extracts.

PMID- 14644323
TI  - Human health concerns with GM crops.
AB  - Biotechnology was used in the first generation of so-called 'GM' crops to provide
      growers with complimentary and sometimes alternative crop management solutions to
      pesticides. Selected host genes or genes identified from other plants or non
      plant sources are modified or transferred to a crop plant. The new or altered
      protein expression resulting from these modifications confer on the plant a
      desired physiological trait, such as resistance to particular herbicides or
      insect pests. Second generation modifications provide traits such as enhanced
      nutritional or health-promoting characteristics that are of benefit to consumers.
      The commonly raised concerns about possible implications for human health are:
      inherent toxicity of the novel gene and their products, the potential to express
      novel antigenic proteins or alter levels of existing protein allergens, the
      potential for unintended effects resulting from alterations of host metabolic
      pathways or over expression of inherently toxic or pharmacologically active
      substances and the potential for nutrient composition in the new food occur
      differing significantly from a conventional counterpart. Foods produced using
      biotechnology are subjected to far greater levels of scrutiny than foods produced
      by traditional plant breeding techniques. The accepted analytical, nutritional
      and toxicological methods employed to support this scrutiny and to assess and
      assure that a 'GM' food is a safe and nutritious as its 'non-GM' counterpart are
      discussed. The challenges associated with identifying unintended effects in whole
      GM foods and the promise new (proteomics/genomic) technologies offer opposite
      traditional toxicity testing paradigms are appraised.

PMID- 14644324
TI  - Genetically modified crops: environmental and human health concerns.
AB  - About 10,000 years ago subsistence farmers started to domesticate plants and it
      was only much later, after the discovery of the fundaments of genetics, those
      organisms were submitted to rational genetic improvement mainly by selecting of
      traits of interest. Breeders used appropriate gene combinations to produce new
      animal races, plant varieties and hybrids, as well as improved microorganisms
      such as yeasts. After the introduction of recombinant DNA techniques, the
      transfer of DNA between species belonging to different genera, families or
      kingdoms became possible. The release of transgenic plants has aroused debates
      about several aspects of the environmental and human risks that could result from
      the introduction of genetically modified crops. Less effort has been dedicated to
      evaluate the impact of transgenic plants on their associated microorganisms, some
      of which (e.g. nitrogen-fixing bacteria, mycorrhizal fungi and endophytic
      microbiota) are extremely important for the survival of the plant. Investigations
      have been made regarding the horizontal transfer of genetic material between
      transgenic plants and microorganisms and on the disturbance of useful symbiotic
      associations between plants and endophytic, epiphytic and rhizosphere
      communities. In most cases the results do no show any adverse effect of
      transgenic plants on autochthonous plant-associated microorganisms. Results from
      our laboratory show small changes caused by genetically modified endophytic
      bacteria on the indigenous endophytic population of the sweet orange Citrus
      sinensis. In tests using appropriated fungal strains preliminary results using
      extracts from transgenic plants indicate that these plants do not affect
      haploidization, mitotic crossing-over, mutation rate or chromosomal alterations.

PMID- 14644325
TI  - Environmental hazards to children's health in the modern world.
AB  - Patterns of illness in children have changed dramatically in the last century,
      and will continue to change in this century. The major diseases confronting
      children are now chronic and disabling conditions termed the "new pediatric
      morbidity"-asthma, leukemia and brain cancer, neurodevelopmental dysfunction and
      neurobehavioral abnormality, reproductive and systemic developmental problems.
      Chemical toxicants in the environment, poverty, and little or no access to health
      care are all factors contributing to life-threatening pediatric diseases;
      children are uniquely vulnerable to chemical toxicants because of their
      disproportionately heavy exposures and their inherent biological growth and
      development. Genetic susceptibility and environmental exposures during vulnerable
      periods of development are also important contributors to the etiologies of many
      diseases of childhood. It is vital that we develop a better understanding of the
      mechanisms and interactions between nutrition, infectious disease, environmental
      exposures, and genetic predisposition in order to develop better prevention
      methods. This paper briefly examines modern contributors to children's
      environmental health problems, efforts to date on both the regional and
      international level to address these challenges, and reflects upon major research
      needs that must be addressed in order to close the gaps that exist in our
      understanding of the relationship between environmental exposures and children's
      health.

PMID- 14644326
TI  - Micronuclei frequency in children exposed to environmental mutagens: a review.
AB  - Cytogenetic monitoring has been traditionally used for the surveillance of
      populations exposed to genotoxic agents. In recent years sensitivity problems
      emerged in surveys of populations exposed to low levels of mutagens, and
      therefore alternative approaches have been explored. Biomonitoring studies in
      children are a promising field, since because of evident differences in the
      uptake, metabolism, distribution and excretion of mutagens this population seems
      to be more susceptible than adults. Further, the effect of major confounders such
      as cigarettes smoking, occupation, life-style, and dietary factors plays a minor
      role. Among cytogenetic assays, the micronucleus assay (MN) has several
      advantages and is increasingly used. A review was then carried out to synthesize
      the published data on the occurrence of MN in children and adolescents (age range
      0-18 years), and to assess the impact of genotoxic exposure on MN frequency.
      Overall, 20 papers from international literature and 8 Russian papers were
      included. An effect of age was found within this age range, while the influence
      of gender on MN frequency was irrelevant. These results were confirmed by the re
      analysis of data for 448 children selected from the HUMN database. An effect of
      chronic and infectious diseases on MN levels has been reported by various
      authors. Most studies describing the effect of exposure to genotoxic agents
      (ionizing radiation, chemicals, drugs, environmental tobacco smoke) found an
      increase of MN in exposed children. The limited number of published papers
      indicates that the conduct of properly designed studies on the effect of
      environmental pollutants in children may be difficult. This review confirmed the
      usefulness of MN assay in biomonitoring studies conducted in children, revealing
      that in many circumstances investigating children increases the sensitivity of
      the study, even with low dose exposures.

PMID- 14644327
TI  - Linking exposure to environmental pollutants with biological effects.
AB  - Exposure to ambient air pollution has been associated with cancer. Ambient air
      contains a complex mixture of toxics, including particulate matter (PM) and
      benzene. Carcinogenic effects of PM may relate both to the content of PAH and to
      oxidative DNA damage generated by transition metals, benzene, metabolism and
      inflammation. By means of personal monitoring and biomarkers of internal dose,
      biologically effective dose and susceptibility, it should be possible to
      characterize individual exposure and identify air pollution sources with relevant
      biological effects. In a series of studies, individual exposure to PM(2.5),
      nitrogen dioxide (NO(2)) and benzene has been measured in groups of 40-50
      subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites
      (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation,
      8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in
      plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone
      reductase (NQO1). With respect to benzene, the main result indicates that DNA
      base oxidation is correlated with PMA excretion. With respect to exposure to PM,
      biomarkers of oxidative damage showed significant positive association with the
      individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative
      damage to lipids and protein in plasma associated with PM(2.5) exposure. Several
      types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand
      breaks and 8-oxodG in lymphocytes increased significantly in the summer period,
      requiring control of confounders. Similar seasonal effects on strand breaks and
      expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported. In
      the present setting, biological effects of air pollutants appear mainly related
      to oxidative stress via personal exposure and not to urban background levels.
      Future developments include personal time-resolved monitors for exposure to
      ultrafine PM and PM(2.5,) use of GPS, as well as genomics and proteomics based
      biomarkers.

PMID- 14644328
TI  - Mutagen sensitivity assays in population studies.
AB  - Human population monitoring studies are frequently conducted to determine if
      exposure to environmental mutagenic agents can cause health problems or not. In
      these studies, a variety of biomarkers are used to identify biological events
      that are predictive of health consequences. An emphasis in this report is on the
      use of mutagen sensitivity assays to understand health risk. The assay is based
      on the assumption that exposure to mutagenic chemicals or mixtures of chemicals
      for a long time can cause cellular changes that are expressed as mutagen
      sensitivity. From experience in using these assays in cancer patients and in
      mutagen-exposed populations, it is clear that the expression of mutagen
      sensitivity is based on the interactions between mutagen exposure and individual
      susceptibility. When studies are conducted under appropriate conditions,
      expression of mutagen sensitivity is suggestive of increased risk for
      environmental disease such as cancer.

PMID- 14644329
TI  - Enhanced sensitivity of peripheral blood lymphocytes from women carrying a BRCA1
      mutation towards the mutagenic effects of various cytostatics.
AB  - We are studying the induction and repair of DNA damage in lymphocytes of women
      from families with familial breast cancer and mutations in the breast cancer
      susceptibility genes BRCA1 and BRCA2. Our previous results indicated a close
      relationship between the presence of a BRCA1 mutation and sensitivity for the
      induction of micronuclei by gamma irradiation and hydrogen peroxide (H2O2). To
      further characterize the mutagen sensitivity and to better understand the
      underlying mechanisms, we now tested the effect of various cytostatics on the
      micronucleus frequencies in lymphocytes of women with various BRCA1 mutations in
      comparison to controls. The results presented here indicate enhanced sensitivity
      towards bleomycin, cisplatin, cyclophosphamide and bischloroethylnitosurea
      (BCNU). However, mutagen sensitivity towards cisplatin and BCNU was not
      accompanied by enhanced induction of sister chromatid exchanges (SCE), suggesting
      that intrachromosomal recombination is not affected. In contrast to the various
      DNA-damaging agents, there was no clear difference in the response to vincristine
      and taxol. FISH analysis revealed that the two aneugens mainly induced centromere
      positive micronuclei to a similar extent in lymphocytes with and without a BRCA1
      mutation. We conclude that cells containing a heterozygous mutation in BRCA1 are
      more sensitive towards different kinds of DNA damage in accordance with the
      proposed central role of BRCA1 in maintaining genomic integrity. Although BRCA1
      has been shown to interact with the mitotic spindle, spindle poisons do not cause
      enhanced induction of micronuclei. Since some of the DNA-damaging mutagens tested
      here are used as cytostatics in breast cancer chemotherapy, it might be that
      women with a BRCA1 mutation are at higher risk for the induction of mutations and
      secondary cancers by standard therapies.

PMID- 14644330
TI  - Response to challenging dose of X-rays as a predictive assay for molecular
      epidemiology.
AB  - Human biomonitoring, as a tool to identify health risk from environmental
      exposures, has gained increasing interest especially in the areas of cancer risk
      assessment and response to therapy. Chromosome aberrations resulting from direct
      DNA breakage or from inhibition of DNA repair or synthesis, as measured in
      peripheral blood lymphocytes, have been used successfully in the assessment of
      environmental health. Susceptibility to the induction of genotoxicity has been
      evaluated by the use of an in vitro challenge dose of UV or X-rays. In this
      report, DNA damage was analyzed with the use of single cell gel electrophoresis
      (SCGE) assay in healthy donors and cancer patients. Studies have shown a good
      correlation between DNA damage induced in vivo or in vitro and cytogenetic
      measures. Results from studies on susceptibilities and repair competence in 475
      controls, exposed workers and cancer patients are discussed. The possible effects
      of exposures and influence of the diet and other confounding factors are shown.
      The prospective use of a challenging dose of radiation combined with the SCGE
      assay as a predictive assay is suggested and the limitations are discussed.

PMID- 14644331
TI  - Formation of chromosome aberrations: insights from FISH.
AB  - Most of the mutagenic and carcinogenic agents induce chromosome aberrations in
      vivo and in vitro. Conventional solid staining (such as Giemsa) has been employed
      to evaluate the frequencies and types of spontaneous and induced chromosomal
      aberrations. Recently, molecular cytogenetic techniques such as fluorescence in
      situ hybridization (FISH) using chromosome specific or chromosome region-specific
      DNA libraries have become available, which have increased the resolution of the
      detection of aberrations. This has lead to a better understanding on the
      mechanisms of formation of chromosome aberrations, especially following treatment
      with ionizing radiation. The present paper reviews briefly the results obtained
      using FISH technique both from basic and applied studies.

PMID- 14644332
TI  - Environment and cancer in Brazil: an overview from a public health perspective.
AB  - This paper presents the current pattern of cancer incidence in Brazil by
      analyzing the country's cancer epidemiological profile. The authors highlight the
      observed overlapping distribution of cancer incidence in Brazil in tumor sites
      normally associated with higher socioeconomic status (cancers of the breast,
      prostate, and colon/rectum, among others) and poverty (cervix, stomach, oral
      cavity, and penis). In addition to analyzing the demographic and social
      characteristics associated with current epidemiological distribution of cancer in
      Brazil, the authors present several of the most important environmental risk
      factors (smoking and exposure to radiation, pesticides, and other chemicals) and
      discuss their respective exposure levels in the Brazilian context. The article
      concludes with an evaluation of the principal challenges facing environmental
      cancer control programs in Brazil, particularly focusing on smoking and exposure
      to chemicals.

PMID- 14644333
TI  - Mutagenic activity as a parameter to assess ambient air quality for protection of
      the environment and human health.
AB  - Atmospheric pollution has significant effects on maintaining the integrity of
      ecosystems and on the population's quality of life. Epidemiological studies have
      clearly associated related health problems, especially respiratory diseases, with
      exposure to air pollution. Organic compounds adsorbed to the airborne particulate
      matter are mutagenic in the Salmonella/microsome assay, and a considerable number
      of them are known to be carcinogenic to rodents. Studies performed at four sites
      within the urban area of Porto Alegre, capital of the state of Rio Grande do Sul,
      identified higher mutagenic activity at the sites with heavier vehicle traffic in
      assays without and with metabolic activation. The responses varied at different
      seasons of the year, and the highest revertants per cubic meter (rev/m(3)) values
      were observed in spring for moderately polar compounds, and in summer for non
      polar ones. A pilot study was also performed in the region under the influence of
      a industrial petrochemical area. Most of the sites studied within the industrial
      area, as compared to others sampled in the nearby environment, presented higher
      levels of mutagenic activity independent of total suspended particulates (TSP)
      concentration in the sample. In the urban and industrial regions, the observed
      mutagenic activities were strongly associated with the presence of polycyclic
      aromatic hydrocarbons (PAHs). The responses observed in the TA98NR and TA98/1,8
      DNP(6) strains suggest the activity of nitrocompounds in both studies. The
      Salmonella/microsome assay is a sensitive method to define areas contaminated by
      these compounds, even in samples with TSP values that are consistent with the
      legal environmental quality standards.

PMID- 14644334
TI  - New revival of an old biomarker: characterisation of buccal cells and
      determination of genetic damage in the isolated fraction of viable leucocytes.
AB  - Buccal cells serve as targets to assess oral exposures. We have refined isolation
      methods to characterise yield, viabilities, types of cells and baseline levels of
      genetic damage. Buccal cells were isolated from mouthwashes of 27 volunteers.
      They were characterised microscopically and different methods (using antibody
      labelled magnetic beads, filtration and gradient centrifugation) were compared to
      separate epithelial cells from leucocytes. Viability of cells, DNA damage, and
      activity of glutathione S-transferase (GST) were measured with dye exclusion,
      microgelelectrophoresis, and biochemically. Mouthwashes contained approximately
      equal amounts of epithelial cells and leucocytes with detectable GST-activities.
      Repetitive determinations with mouthwashes from four individuals yielded per
      sample (3.5+/-1.4)x10(6) epithelial cells and (4.7+/-3.9)x10(6) leucocytes with
      viabilities of 8 and 94%, respectively. Epithelial cells could not be isolated
      using antibody-labelled beads, but cell separation with the leukocyte-specific
      antibody CD45 succeeded, yielding 37% leucocytes with a purity of 95% and
      viability of 65%. Filtering the mouthwash through a 10 microm filter yielded 57%
      leucocytes, with 86% purity and 94% viability. When using density gradient
      centrifugation as the separation method, the recovery of leucocytes was low
      (22%), but good results were scored for purity (95%) and cell viability (88%).
      This method was used to isolate leucocytes, which were then subjected to a micro
      scale comet assay-modification. It was found that buccal leucocytes obtained from
      smokers had more DNA damage than cells from non-smokers. In conclusion,
      suspensions of buccal cells consist in approximately equal parts of epithelial
      cells and leucocytes. Only leucocytes are sufficiently viable for measuring
      parameters of cytotoxicity and genotoxicity or for studying modulation of gene
      expression. The cells are useful targets of non-invasive biomarkers, which could
      be incorporated as tools in many types of intervention studies.

PMID- 14644335
TI  - Community outreach as an iterative dialogue among scientists and communities in
      the Texas gulf coast region.
AB  - In response to significant environmental health challenges in Southeast Texas, a
      National Institute for Environmental Health Sciences Center at the University of
      Texas Medical Branch at Galveston was created to promote and conduct inter
      disciplinary research in the areas of: (1) the molecular biology of DNA repair,
      replication and mutagenesis, (2) asthma pathogenesis in response to oxidative
      stress and viral exposures, and (3) environmental toxicant biotransformation. In
      addition, the NIEHS Center maintains close ties with neighboring communities
      through an active Community Outreach & Education Program (COEP) that develops and
      disseminates translational materials for use in environmental health awareness
      outreach, toxicology consultation, K-12 curriculum enrichment and in developing
      site-specific Community Partnership projects. The COEP core service divisions
      include: Environmental Arts & Sciences, Asthma Outreach & Education, Theater
      Outreach & Education, and Public Forum & Toxics Assistance. Public Forums focus
      on the use of Augusto Boal's Forum Theater dramaturgy to include the voices and
      local knowledge of communities within the process of Participatory Research.
      Forums create the preconditions for significant partnerships that link the
      hazardous risk perceptions and environmental health needs of communities with the
      expertise of NIEHS Center investigators and translational services provided
      through COEP outreach programs. The Forum process also creates leadership cores
      within environmentally challenged communities that facilitate the ongoing
      translational process and maintain the vital linkage between the health needs of
      communities and the analytic tools and the field and clinical technologies of the
      environmental sciences.

PMID- 14644336
TI  - Genetic susceptibility, biomarker respones, and cancer.
AB  - A large number of studies have reported associations between polymorphisms of
      xenobiotic-metabolizing enzymes (XMEs) and various cancers. However, the
      carcinogenic exposures behind such findings have usually been unclear.
      Information on susceptibility to specific carcinogens could better be obtained by
      examining situations where the exposure and the endpoint studied are nearer in
      time, i.e., by studying biomarkers of carcinogen exposure and early (genotoxic)
      effect in exposed humans. For example, analyses of DNA adducts and cytogenetic
      endpoints have indicated an increased susceptibility of glutathione S-transferase
      M1 (GSTM1) null genotype to genotoxicity of tobacco smoking, supporting the view
      that the associations of the GSTM1 null genotype with bladder and lung cancer are
      partly related to smoking. In vitro genotoxicity studies with human cells offer
      an experimental tool that can be used, within the limits of the cell systems, to
      predict individual sensitivity and genotype-carcinogen interactions. In vitro
      sensitivity to the genotoxicity of 1,2:3,4-diepoxybutane, an epoxide metabolite
      of 1,3-butadiene has clearly been shown to depend on GSTT1 genotype, which has
      also been implicated to modify, along with GSTM1 genotype, the in vitro
      genotoxicity of 1,2-epoxy-3-butene, another epoxide metabolite of 1,3-butadiene.
      These genotypes appear to modulate the excretion of 1,3-butadiene-specific
      mercapturic acids, and influence genotoxicity biomarker levels in 1,3-butadiene
      exposed workers. The excretion of specific mercapturic acids (PHEMA) in workers
      exposed to styrene has clearly been shown to depend on GSTM1 genotype, and GSTT1
      genotype seems to modulate the excretion of one PHEMA diastereoisomer. These
      genotypes have also been implicated to modulate the in vitro genotoxicity of
      styrene. In general, the genetic polymorphisms potentially important for
      biomarker response largely depend on the exposing agent, biological material
      examined, and ethnicity of the population under study. Individual exposure level
      may vary a lot, and a reliable estimate of the exposure is essential for correct
      interpretation of genotype-exposure interaction. Besides XME polymorphisms, any
      polymorphisms that affect cellular response to DNA damage could, in principle,
      modify individual sensitivity to genotoxins. For instance, those concerning DNA
      repair proteins are presently being studied by many laboratories.

PMID- 14644337
TI  - The impact of new technologies on human population studies.
AB  - Human population studies involve clinical or epidemiological observations that
      associate environmental exposures with health endpoints and disease. Clearly,
      these are the most sought after data to support assessments of human health risk
      from environmental exposures. However, the foundations of many health risk
      assessments rest on experimental studies in rodents performed at high doses that
      elicit adverse outcomes, such as organ toxicity or tumors. Using the results of
      human studies and animal data, risk assessors define the levels of environmental
      exposures that may lead to disease in a portion of the population. These
      decisions on potential health risks are frequently based on the use of default
      assumptions that reflect limitations in our scientific knowledge. An important
      immediate goal of toxicogenomics, including proteomics and metabonomics, is to
      offer the possibility of making decisions affecting public health and public
      based on detailed toxicity, mechanistic, and exposure data in which many of the
      uncertainties have been eliminated. Ultimately, these global technologies will
      dramatically impact the practice of public health and risk assessment as applied
      to environmental health protection. The impact is already being felt in the
      practice of toxicology where animal experimentation using highly controlled dose
      time parameters is possible. It is also being seen in human population studies
      where understanding human genetic variation and genomic reactions to specific
      environmental exposures is enhancing our ability to uncover the causes of
      variations in human response to environmental exposures. These new disciplines
      hold the promise of reducing the costs and time lines associated with animal and
      human studies designed to assess both the toxicity of environmental pollutants
      and efficacy of therapeutic drugs. However, as with any new science, experience
      must be gained before the promise can be fulfilled. Given the numbers and
      diversity of drugs, chemicals and environmental agents; the various species in
      which they are studied and the time and dose factors that are critical to the
      induction of beneficial and adverse effects, it is only through the development
      of a profound knowledge base that toxicology and environmental health can rapidly
      advance. The National Institute of Environmental Health Sciences (NIEHS),
      National Center for Toxicogenomics and its university-based Toxicogenomics
      Research Consortium (TRC), and resource contracts, are engaged in the
      development, application and standardization of the science upon which to the
      build such a knowledge base on Chemical Effects in Biological Systems (CEBS). In
      addition, the NIEHS Environmental Genome Project (EGP) is working to
      systematically identify and characterize common sequence polymorphisms in many
      genes with suspected roles in determining chemical sensitivity. The rationale of
      the EGP is that certain genes have a greater than average influence over human
      susceptibility to environmental agents. If we identify and characterize the
      polymorphism in those genes, we will increase our understanding of human disease
      susceptibility. This knowledge can be used to protect susceptible individuals
      from disease and to reduce adverse exposure and environmentally induced disease.

PMID- 14644338
TI  - Acquired and genetic susceptibility to cervical cancer.
AB  - Infection with high-risk human papilloma virus (HPV) is a necessary risk factor
      for the development of cervical cancer (CC). However, there are many factors that
      contribute to the development of CC. We have been investigating the role of
      polymorphisms in chemical metabolizing genes and life-style factors in the
      development of CC between two countries with significantly different prevalence
      of CC. Our data confirm that infection with high-risk HPV is the most significant
      risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex
      partners and early sexual activities are significant risk factors (OR=4.7, 95%
      CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette
      smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8
      23.2). Genotype analyses were conducted using specimens from the US population
      only. The GSTM1 null genotype was associated with a significant 3.4 fold increase
      in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after
      adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are
      associated with a non-significant increase in risk. Our study indicates that
      different acquired and genetic susceptibility factors can make significant
      contributions to the development of environmental disease such as cervical
      cancer.

PMID- 14644339
TI  - Mechanisms of esophageal cancer development in Brazilians.
AB  - Esophageal cancer represents one of the most common and lethal cancers around the
      World. Some areas of South America, including parts of Brazil, present the
      highest incidence of the disease in the West. The main etiological factors that
      have been associated with the disease in Brazil are alcohol consumption, tobacco
      smoking and, in the South, consumption of hot mate. Nitrosamines are the only
      carcinogens capable of inducing tumors in the esophagus of experimental animals,
      with the rat being the most susceptible species, mainly due to tissue specific
      metabolic activation by CYP enzymes. Studies of CYP2A expression in the esophagus
      of rodents suggest an association between CYP2A expression and esophageal
      susceptibility to tumor induction. CYP2A6 and CYP2E1, the main enzymes to
      activate nitrosamines in humans, are the only carcinogen activating CYP enzymes
      to be expressed in the esophagus of Brazilians. Patients who presented high
      levels of CYP2A6 expression could activate nitrosamines at rates comparable to
      the rat. This expression profile is different from those present in French
      patients. We investigated 34 Brazilian patients regarding the risk associated
      with polymorphisms in drug metabolizing enzymes and TP53 mutations. A GSTP1
      polymorphism presented a clear risk to white and non-white patients to develop
      esophageal cancer. GSTM1 null polymorphism also seemed to be associated with an
      increased risk. CYP2A6, CYP2E1, SOD2, and GSTT1 polymorphisms were not associated
      with an increased risk of esophageal cancer. TP53 mutations occurred mostly in
      exon 7, differing from the mutation profile found in the IARC database. The
      preliminary results obtained with polymorphisms of drug metabolizing enzymes and
      TP53 mutations need to be confirmed in a larger number of samples in order to
      compare the mechanisms of esophageal cancer development in Brazilians with that
      of other populations.

PMID- 14644340
TI  - Genetic susceptibility to infection with human papillomavirus and development of
      cervical cancer in women in Brazil.
AB  - Human papillomavirus (HPV) is considered to be a necessary but not sufficient
      cause for cervical cancer and, therefore, other factors contribute to the
      carcinogenic process. A hereditary component for this neoplasia has been reported
      and several studies indicate that genetic background of the host is important for
      cervical cancer susceptibility. Among genetic factors that could participate in
      the susceptibility to this tumor and disease outcome, polymorphic genes of the
      major histocompatibility complex (MHC), as well as a particular polymorphism in
      the p53 gene have been intensely investigated. From our analysis of 613 samples
      in Brazil, we found evidence to indicate that different polymorphic human
      leukocyte antigen (HLA) genes are involved in the clearance and maintenance of
      HPV infection. In addition, the homozygous codon 72 p53-Arg gene allele is
      associated with susceptibility to HPV-associated cervical carcinogenesis.
      However, supportive and opposing data have been reported in different
      populations. Therefore, international collaborative studies need to be conducted
      to define the consistency of the associations described.

PMID- 14644341
TI  - Implementation of a molecular epidemiology approach to human pleural malignant
      mesothelioma.
AB  - The carcinogenic effect of asbestos has been reported in the literature since 40
      years, and early studies describing the epidemic occurrence of malignant
      mesothelioma (MM) in asbestos workers, have become a paradigm of occupational
      cancer research. Research on MM was abandoned for many years since MM was
      considered as an asbestos-related disease, interesting only from a perspective of
      disease control and preventive policies. The introduction of new biological
      endpoints in the epidemiological studies has boosted research in the field,
      providing new tools for the study of emerging priority in cancer research and in
      public health. This approach, known as molecular epidemiology has a great
      potential in the study of MM, contributing to the understanding of susceptibility
      factors, to the evaluation of cancer risk in people occupationally or
      environmentally exposed to carcinogens, and to the enhancement of diagnosis and
      therapy. A comprehensive approach based on the use of banks of biological samples
      is presented and its advantages discussed here. The application of innovative
      endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or
      gene function is discussed, and relevant literature reviewed.

PMID- 14644342
TI  - Molecular epidemiology studies of carcinogenic environmental pollutants. Effects
      of polycyclic aromatic hydrocarbons (PAHs) in environmental pollution on
      exogenous and oxidative DNA damage.
AB  - Exposure to high levels of environmental air pollution is known to be associated
      with an increased carcinogenic risk. The individual contribution to this risk
      derived from specific carcinogenic chemicals within the complex mixture of air
      pollution is less certain, but may be explored by the use of molecular
      epidemiological techniques. Measurements of biomarkers of exposure, of effect and
      of susceptibility provide information of potential benefit for epidemiological
      and cancer risk assessment. The application of such techniques has been mostly
      concerned in the past with the carcinogenic polycyclic aromatic hydrocarbons (c
      PAHs) that are associated with particulate matter in air pollution, and has
      showed clear evidence of genotoxic effects, such as DNA adducts, chromosome
      aberrations (CA) and ras oncogene overexpression, in environmentally exposed
      Czech and Polish populations. We are currently extending these studies by an
      investigation of populations exposed to environmental pollution in three European
      countries, Czech Republic, Slovak Republic and Bulgaria. This pays particular
      attention to PAHs, but also investigates the extent of radically induced
      (oxidative) DNA damage in the exposed populations. Policemen, bus drivers and
      controls, who carried personal monitors to determine their exposures to PAHs have
      been studied, and blood and urine were collected. Antioxidant and dietary status
      were assessed in these populations. Stationary monitors were also used for
      ambient air monitoring. Amongst the parameters studied in the biological samples
      were: (a) exposure biomarkers, such as PAH adducts with DNA, p53 and p21(WAF1)
      protein levels, (b) oxidative DNA damage, (c) the biological effect of the
      exposure by measurement of chromosome damage by fluorescence in situ
      hybridisation (FISH) or conventional methods, and (d) polymorphisms in carcinogen
      metabolising and DNA repair enzymes. Repair ability was also measured by the
      Comet assay. In vitro systems are being evaluated to characterise the
      genotoxicity of the organic compounds adsorbed to air particles.

PMID- 14644343
TI  - Gene expression profiles in human cells submitted to genotoxic stress.
AB  - Cell response to genotoxic agents is complex and involves the participation of
      different classes of genes (DNA repair, cell cycle control, signal transduction,
      apoptosis and oncogenesis). In this report, we present three approaches to
      document gene expression profiles, dealing with the evaluation of cellular
      responses to genotoxic agents (gamma-rays from 60Cobalt and cyclophosphamide). We
      used the method of cDNA arrays to analyze the differential gene expression
      profiles that were displayed by lymphocytes from radiation-exposed individuals, a
      human fibroblast cell line, and T lymphocytes from systemic lupus erythematosus
      (SLE) patients who were treated with cyclophosphamide. A preliminary analysis
      performed in lymphocytes from three radiation-workers showed that several induced
      genes can be associated with cell response to ionizing radiation: TRRAP (cell
      cycle regulation), Ligase IV (DNA repair), MAPK8IP1 and MAPK10 (signal
      transduction), RASSF2 (apoptosis induction/tumorigenesis), p53 (damage
      response/maintenance of genetic stability). The in vitro irradiated normal VH16
      cell line (primary) showed a complex response to the genotoxic stress at the
      molecular level. Many apoptotic pathways were concomitantly induced. In addition,
      several genes involved in signaling and cell cycle arrest/control were
      significantly modulated after irradiation. Many genes involved in oxidative
      damage were also induced, indicating that this mechanism seems to be an important
      component of cell response. After treatment of the SLE patients with
      cyclophosphamide, 154 genes were differentially and significantly induced. Among
      them, we identified those associated with drug detoxification, cell cycle
      control, apoptosis, and tumor-suppressor. These findings indicate that at least
      two apoptotic pathways were induced after cyclophosphamide treatment. The
      induction of APAF1 and two genes coding for two subunits of cytochrome c supports
      a previous report showing increased apoptosis in lymphocytes from SLE patients.
      The present study provides new information on the molecular mechanism underlying
      the cell response to genotoxic stress, with relevance to basic and clinical
      research.

PMID- 14644344
TI  - Toxicogenomic approach for assessing toxicant-related disease.
AB  - The problems of identifying environmental factors involved in the etiology of
      human disease and performing safety and risk assessments of drugs and chemicals
      have long been formidable issues. Three principal components for predicting
      potential human health risks are: (1) the diverse structure and properties of
      thousands of chemicals and other stressors in the environment; (2) the time and
      dose parameters that define the relationship between exposure and disease; and
      (3) the genetic diversity of organisms used as surrogates to determine adverse
      chemical effects. The global techniques evolving from successful genomics efforts
      are providing new exciting tools with which to address these intractable problems
      of environmental health and toxicology. In order to exploit the scientific
      opportunities, the National Institute of Environmental Health Sciences has
      created the National Center for Toxicogenomics (NCT). The primary mission of the
      NCT is to use gene expression technology, proteomics and metabolite profiling to
      create a reference knowledge base that will allow scientists to understand
      mechanisms of toxicity and to be able to predict the potential toxicity of new
      chemical entities and drugs. A principal scientific objective underpinning the
      use of microarray analysis of chemical exposures is to demonstrate the utility of
      signature profiling of the action of drugs or chemicals and to utilize microarray
      methodologies to determine biomarkers of exposure and potential adverse effects.
      The initial approach of the NCT is to utilize proof-of-principle experiments in
      an effort to "phenotypically anchor" the altered patterns of gene expression to
      conventional parameters of toxicity and to define dose and time relationships in
      which the expression of such signature genes may precede the development of overt
      toxicity. The microarray approach is used in conjunction with proteomic
      techniques to identify specific proteins that may serve as signature biomarkers.
      The longer-range goal of these efforts is to develop a reference relational
      database of chemical effects in biological systems (CEBS) that can be used to
      define common mechanisms of toxicity, chemical and drug actions, to define
      cellular pathways of response, injury and, ultimately, disease. In order to
      implement this strategy, the NCT has created a consortium of research
      organizations and private sector companies to actively collaborative in
      populating the database with high quality primary data. The evolution of discrete
      databases to a knowledge base of toxicogenomics will be accomplished through
      establishing relational interfaces with other sources of information on the
      structure and activity of chemicals such as that of the National Toxicology
      Program (NTP) and with databases annotating gene identity, sequence, and
      function.

PMID- 14644345
TI  - Transgenerational carcinogenesis: induction and transmission of genetic
      alterations and mechanisms of carcinogenesis.
AB  - Parental exposure, i.e. germ cell exposure to radiation and chemicals, increased
      the incidence of tumors and malformations in the offspring, and the germ-line
      alterations that cause cancer are transmissible to further generations. However,
      tumor incidences were 100-fold higher than those of ordinary mouse mutations and
      there were apparent strain differences in the types of induced tumors. In human,
      higher risk of leukemia is reported in the children of fathers who had been
      exposed to radionuclides at the nuclear reprocessing plants or to diagnostic
      doses of radiation. However, these findings in mice and men have not been
      confirmed in the children of atomic bomb survivors in Hiroshima and Nagasaki.
      Another important finding was that germ-line exposure was very weakly tumorigenic
      by itself. However, the transmissible alterations caused persistent
      hypersensitivity to tumor induction in the offspring, e.g. enhanced by postnatal
      treatment with tumor promoting/carcinogenic agents. The above results suggest
      that transmissible alterations might be imprinted in germ cells for the future
      development of cancer by the postnatal environment. Many gene loci concerning
      immunological, biochemical and physiological function might be involved, and the
      cumulative changes in such genes may slightly elevate or enhance tumor
      incidences, although mutations of tumor suppressor genes such as p53 were also
      detected in some offspring and genomic instability may modify tumor occurrence in
      transgenerational manner. In fact, Gene Chip analysis showed suppression and/or
      over-expression of many functional genes rather than cancer-related genes in the
      preconceptionally irradiated cancer prone progeny.

PMID- 14644346
TI  - Long-term genetic effects of radiation exposure.
AB  - To date, there has been little experimental knowledge on the genetic risks of
      human exposure to ionising radiation for humans. Recent data suggest that
      hypervariable tandem repeat minisatellite loci provide a useful and sensitive
      experimental approach for monitoring radiation-induced germline mutation in
      humans. Here, I review the results of studies on minisatellite mutation rates in
      human populations exposed to radioactive fallout after the Chernobyl accident and
      nuclear weapon tests in Kazakhstan.

PMID- 14644347
TI  - Birth-related genomic and transcriptional changes in mouse lung. Modulation by
      transplacental N-acetylcysteine.
AB  - Birth is characterized by a sudden transition from the maternal-mediated
      respiration to the autonomous pulmonary respiration. Notwithstanding the
      importance of the involved functional and metabolic changes, little is known
      about possible DNA alterations occurring in the lung during the perinatal period.
      We comparatively evaluated genomic and transcriptional changes in the lung of
      fetuses and newborn Swiss albino mice, whose dams had either been untreated or
      treated with oral N-acetyl-L-cysteine (NAC) throughout the pregnancy period. In
      the less than 24h period elapsing between the end of fetal life and the start of
      post-natal life, nucleotide alterations occurred in mouse lung, as shown by a
      significant increase of both bulky DNA adducts and 8-hydroxy-2'-deoxyguanosine
      levels, detected by 32P post-labeling procedures. The frequency of micronuclei in
      peripheral blood erythrocytes was not significantly increased after birth.
      Multigene expression analysis of 746 selected genes, by cDNA arrays, showed that
      33 of them (4.4%) were upregulated in the lung of newborn mice, as compared with
      fetuses. The overexpressed genes were mainly involved in protective mechanism as
      a response to oxidative changes, alterations of glutathione metabolism, cellular
      stress, and damage to DNA and proteins. The transplacental treatment with NAC
      totally prevented birth-related genomic alterations in lung DNA. NAC did not
      change the basal gene expression in mouse fetal lung, but attenuated the
      upregulation of most genes involved in oxidative stress, stress response, and DNA
      repair in the lung of newborn mice. In fact, only 13 genes (1.7%) were
      overexpressed in newborns from NAC-treated dams. It therefore appears that
      administration of NAC during pregnancy is beneficial not only to counteract the
      adverse effects of toxic agents, as supported by previous studies, but also to
      attenuate birth-related DNA alterations.

PMID- 14644348
TI  - Ameliorating effect of beta-carotene on ethylmethane sulphonate-induced
      genotoxicity in the fish Oreochromis mossambicus.
AB  - Genotoxic effects have been assessed in the fish Oreochromis mossambicus treated
      separately and conjointly with 0.2% ethylmethane sulphonate (EMS) and 0.05% beta
      carotene (BC) during five different time periods (6, 24, 48, 72 and 96 h) by
      analysis of endpoints such as chromosome aberrations, abnormal red blood cell
      nuclei, abnormal sperm morphology and protein contents (both qualitative and
      quantitative) of selected tissues, viz. muscle, heart, eye, brain, gill, liver,
      spleen and kidney. In addition, the relative efficacy of three doses of BC 0.02,
      0.05 and 0.1%, in ameliorating genotoxic effects of 0.2% EMS was also tested
      after a treatment period of 48 h. EMS caused chromosomal aberrations, nuclear
      anomalies in red blood cells, abnormal sperm morphology and an apparent
      alteration of protein synthesis in various tissues. Some of these genotoxic
      effects of EMS appeared to be ameliorated by all three doses of BC, of which the
      0.02% dose showed a marginally better efficacy.

PMID- 14644349
TI  - Detection of oxidative DNA damage in isolated marine bivalve hemocytes using the
      comet assay and formamidopyrimidine glycosylase (Fpg).
AB  - Organisms in polluted areas can be exposed to complex mixtures of chemicals;
      however, exposure to genotoxic contaminants can be particularly devastating. DNA
      damage can lead to necrosis, apoptosis, or heritable mutations, and therefore has
      the potential to impact populations as well as individuals. Single cell gel
      electrophoresis (the comet assay) is a simple and sensitive technique used to
      examine DNA damage in single cells. The lesion-specific DNA repair enzyme
      formamidopyrimidine glycoslyase (Fpg) can be used in conjunction with the comet
      assay to detect 8-oxoguanine and other damaged bases, which are products of
      oxidative damage. Fpg was used to detect oxidative DNA damage in experiments
      where isolated oyster (Crassostrea virginica) and clam (Mercenaria mercenaria)
      hemocytes were exposed to hydrogen peroxide. Standard enzyme buffers used with
      Fpg and the comet assay produced unacceptably high amounts of DNA damage in the
      marine bivalve hemocytes used in this study necessitating a modification of
      existing methods. A sodium chloride based reaction buffer was successfully used.
      Oxidative DNA damage can be detected in isolated oyster and clam hemocytes using
      Fpg and the comet assay when the sodium chloride reaction buffer and protocols
      outlined here are employed. The use of DNA repair enzymes, such as Fpg, in
      conjunction with the comet assay expands the usefulness and sensitivity of this
      assay, and provides important insights into the mechanisms of DNA damage.

PMID- 14644350
TI  - Genotoxicity of 2,4-D and dicamba revealed by transgenic Arabidopsis thaliana
      plants harboring recombination and point mutation markers.
AB  - The phenoxy herbicides 2,4-D and dicamba are released daily into the environment
      in large amount. The mechanisms of genotoxicity and mutagenicity of these
      herbicides are poorly understood, and the available genotoxicity data is
      controversial. There is a cogent need for a novel genotoxicity monitoring system
      that could provide both reliable information at the molecular level, and
      complement existing systems.We employed the transgenic Arabidopsis thaliana
      'point mutation' and 'recombination' plants to monitor the genetic effects of the
      herbicides 2,4-D and dicamba. We found that both herbicides had a significant
      effect on the frequency of homologous recombination A-->G mutation. Neither
      herbicides affected the T-->G mutation frequency. Interestingly, these transgenic
      biomonitoring plants were able to detect the presence of phenoxy herbicides at
      concentrations that were lower than the guideline levels for Drinking Water
      Quality. The results of our studies suggest that our transgenic system may be
      ideal for the evaluation of the genotoxicity of herbicide-contaminated water.
      Moreover, the unique ability of the plants to detect both double-strand breaks
      (homologous recombination) and point mutations provides tremendous potential in
      the study of molecular mechanisms of genotoxicity and mutagenicity of phenoxy
      herbicides.

PMID- 14644351
TI  - Investigations on the effect of cigarette smoking in the comet assay.
AB  - The comet assay (single-cell gel electrophoresis, SCG) is widely accepted as an
      in vitro and in vivo genotoxicity test. Because of its demonstrated ability to
      detect various kinds of DNA damage and its ease of application, the technique is
      being increasingly used in human biomonitoring. However, the assessment of small
      genotoxic effects as typically obtained in biomonitoring may be limited by the
      different sources of assay variability and the lack of an optimal protocol with
      high sensitivity. To better characterize the suitability of the comet assay for
      biomonitoring, we are performing a comprehensive investigation on blood samples
      from smokers and non-smokers. Because tobacco smoke is a well-documented source
      of a variety of potentially mutagenic and carcinogenic compounds, smokers should
      be a suitable study group with relevant mutagen exposure. Here, we report our
      results for the first sample of 20 healthy male smokers and 20 healthy male non
      smokers. Baseline and benzo[a]pyrene diolepoxide (BPDE)-induced effects were
      analysed by two investigators using two image analysis systems. The study was
      repeated within 4 months. Furthermore, the influence of a repair inhibitor
      (aphidicolin, APC) on baseline and BPDE-induced DNA damage was comparatively
      analysed. In all experiments, a reference standard (untreated V79 cells) was
      included to correct for assay variability. None of these approaches revealed
      significant differences between smokers and non-smokers. Although more data is
      needed for a final conclusion, this study indicates some limitations of the comet
      assay with regard to the detection of DNA damage induced by environmental
      mutagens in peripheral blood cells.

PMID- 14644352
TI  - Genotoxic activity of four metabolites of the soy isoflavone daidzein.
AB  - Products containing phytoestrogens are increasingly promoted as the "natural"
      alternative to estrogen replacement therapy. In the present study, we have used
      the in vitro micronucleus assay in L5178Y mouse lymphoma cells to investigate the
      genotoxic potential of the isoflavone daidzein, and of four daidzein metabolites
      known to be formed in humans. Whereas no induction of micronuclei was observed
      with daidzein up to the limit of solubility (100 microM), all four daidzein
      metabolites, i.e. equol (2.3-fold induction at 100 microM), O-desmethylangolensin
      (6.2-fold induction at 10 microM), 4',6,7-isoflavone (6.7-fold induction at 100
      microM) and 3',4',7-isoflavone (8.2-fold induction at 100 microM) induced
      micronuclei in a concentration-dependent manner. Thus, both reductive and
      oxidative metabolites of the soy isoflavone daidzein exhibit genotoxic potential
      in vitro.

PMID- 14644353
TI  - Bacterial antimutagenesis by hydroxycinnamic acids from plant cell walls.
AB  - We have determined the abilities of (E)-ferulic acid, (E)-p-coumaric acid and
      (E,E)-5-5-dehydrodiferulic acid to protect against different types of mutation in
      a simple bacterial model. These antimutagenic properties were compared with those
      of the related compound curcumin, and also with those of an extract containing
      hydroxycinnamic acids obtained by the saponification of the cell walls of wheat
      coleoptiles. Three known mutagens, bleomycin, hydrogen peroxide and 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) were used to chemically induce reversion
      mutation, while the known antimutagen Trolox was used as a positive control. Both
      the pure hydroxycinnamic acids and the extract from the cell walls showed
      antimutagenic properties. It is known that hydroxycinnamic acids ester-linked to
      plant cell walls can be released in the human colon by the action of microbial
      esterases. Providing the current data extrapolate to mammalian cells, they
      suggest that antimutagenic properties of hydroxycinnamic acids released from
      plant cell walls could play a role in dietary fibre protection against cancer.

PMID- 14644354
TI  - Propofol anesthesia in children does not induce sister chromatid exchanges in
      lymphocytes.
AB  - BACKGROUND: Propofol is frequently used for general anesthesia in children
      although little is known about possible genotoxic effects in humans. We
      investigated the formation of sister chromatid exchanges (SCE) in metaphase
      chromosomes of T-lymphocytes of children as a marker for possible genotoxocity
      following total intravenous anesthesia with propofol for minor surgical
      procedures. METHODS: 40 children ASA classification I-III were included (ASA I
      n=34, ASA II n=5, ASA III n=1) in the study. Anesthesia was induced by propofol
      (3mg/kg) and alfentanil. Succinylcholine or rocuronium were administered for
      muscle relaxation. After tracheal intubation anesthesia was maintained by
      continuous propofol infusion at 12 mg/(kgh). Blood samples were drawn before
      induction and after termination of anesthesia. Following a 72 h cell culture
      period, 25 T-lymphocyte metaphases per blood sample for all children were
      analyzed for SCE frequencies. RESULTS: Total intravenous anesthesia with propofol
      on children did not influence SCE rates in metaphase chromosomes of T
      lymphocytes. No SCE differences could be detected between blood samples before
      initiation and after termination of anesthesia (Wilcoxon signed rank test).
      Slightly elevated SCE rates were obtained in T-lymphocytes of girls compared to
      boys, but these differences did not reach statistical significance. CONCLUSIONS:
      Propofol anesthesia under the chosen conditions did not induce the formation of
      SCE in children in vivo. No genotoxic effect of a short term exposure to propofol
      during pediatric anesthesia had been observed.

PMID- 14644355
TI  - Differential effects in cells exposed to ultra-short, high intensity electric
      fields: cell survival, DNA damage, and cell cycle analysis.
AB  - High power, nanosecond pulsed electric field (nsPEF) effects have been focused on
      bacterial decontamination, but the impact on mammalian cells is now being
      revealed. During nsPEF applications, electrical pulses of 10, 60 or 300 ns
      durations were applied to cells using electric field amplitudes as high as 300
      kV/cm. Because of the ultra-short pulse durations, the energy transferred to
      cells is negligible, and only non-thermal effects are observed. We investigated
      the genotoxicity of nsPEF on adherent and non-adherent cell lines including 10
      human lines and one mouse cell line with different origin and growth
      characteristics. We present data examining the effects of nsPEF exposure on cell
      survival assessed by clonogenic formation or live cell count; DNA damage
      determined by the comet assay and chromosome aberrations; and cell cycle
      parameters by measuring the mitotic indices of exposed cells. Using each of these
      indicators, we observed differential effects among cell types with non-adherent
      cells being more sensitive to the genotoxic effects of nsPEF exposures than
      adherent cells. Non-adherent cultures showed a rapid decrease in cell viability
      (90%), induction of DNA damage, and a decrease in the number of cells reaching
      mitosis after one 60 ns pulse with an electric field intensity of 60 kV/cm. These
      effects were not observed in cells grown as adherent cultures, with the exception
      of the mouse 3T3 cell line, which showed survival characteristics similar to non
      adherent cultures. These data suggest that nsPEF genotoxicity may be cell type
      specific, and therefore have potential applications in the selective removal of
      one cell type from another, for example, in diseased states.

PMID- 14644356
TI  - Micronucleated CD71-positive reticulocytes: a blood-based endpoint of cytogenetic
      damage in humans.
AB  - The frequency of micronuclei (also known as Howell-Jolly bodies) in peripheral
      blood erythrocytes of humans is extremely low due to the efficiency with which
      the spleen sequesters and destroys these aberrant cells. In the past, this has
      precluded erythrocyte-based analyses from effectively measuring chromosome
      damage. In this report, we describe a high-throughput, single-laser flow
      cytometric system for scoring the incidence of micronucleated reticulocytes (MN
      RET) in human blood. Differential staining of these cells was accomplished by
      combining the immunochemical reagent anti-CD71-FITC with a nucleic acid dye
      (propidium iodide plus RNase). The immunochemical reagent anti-CD42b-PE was also
      incorporated into the procedure in order to exclude platelets which can interfere
      with analysis. This analytical system was evaluated with blood samples from ten
      healthy volunteers, one splenectomized subject, as well as samples collected from
      nine cancer patients before and over the course of radio- or chemotherapy. The
      mean frequency of MN-RET observed for the healthy subjects was 0.09%. This value
      is nearly two orders of magnitude higher than frequencies observed in mature
      erythrocytes, and is approximately half the MN-RET frequency observed for the
      splenectomized subject (0.20%). This suggests that the spleen's effect on
      micronucleated cell incidence can be minimized by restricting analyses to the
      youngest (CD71-positive) fraction of reticulocytes. Furthermore, MN-RET
      frequencies were significantly elevated in patients undergoing cancer therapy.
      Collectively, these data establish that micronuclei can be quantified in human
      peripheral blood reticulocytes with a single-laser flow cytometer, and that these
      measurements reflect the level of chromosome damage which has occurred in red
      marrow space.

PMID- 14644357
TI  - Inhibitory effects of chlorophyllin, hemin and tetrakis(4-benzoic acid)porphyrin
      on oxidative DNA damage and mouse skin inflammation induced by 12-O
      tetradecanoylphorbol-13-acetate as a possible anti-tumor promoting mechanism.
AB  - Reactive oxygen species (ROS) from both endogenous and exogenous sources can
      cause oxidative DNA damage and dysregulated cell signaling, which are involved in
      the multistage process of carcinogenesis such as tumor initiation, promotion and
      progression. A number of structurally different anticarcinogenic agents inhibit
      inflammation and tumor promotion as they reduce ROS production and oxidative DNA
      damage. Evidence suggests that porphyrins can interfere with the actions of
      various carcinogens and mutagens by forming face-to-face complexes and their
      antimutagenic or antigenotoxic effects may also be attributed to their
      antioxidant activities. However, little is known regarding the anti-tumor
      promoting potential and mechanism of the porphyrin compounds. Based on our
      previous results on the inhibitory effects of chlorophyllin (CHL), hemin and
      tetrakis(4-benzoic acid)porphyrin (TBAP) against two-stage mouse skin
      carcinogenesis, we have investigated their anti-tumor promoting mechanisms. In
      the present work, CHL, hemin and TBAP reduced superoxide anion generation by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in differentiated HL-60 cells and the
      production of hydroxyl radicals by Fenton reaction. Porphyrins exert a dose
      related inhibition of his(+) reversion in Salmonella typhimurium TA102 induced by
      tert-butylhydroperoxide (t-BOOH). DNA strand breaks by ROS derived from
      H(2)O(2)/Cu(II) and the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf
      thymus DNA treated with H(2)O(2)/UV also were inhibited markedly by porphyrins in
      a concentration-dependent manner. Furthermore, CHL, hemin and TBAP decreased
      myeloperoxidase (MPO) activity and H(2)O(2) formation as well as epidermal
      ornithine decarboxylase (ODC) activity in mouse skin treated with TPA. These
      results demonstrate that the antioxidative properties of porphyrins are important
      for inhibiting TPA-induced tumor promotion.

PMID- 14644358
TI  - Ascorbic acid reduces the frequency of iron induced micronuclei in bone marrow
      cells of mice.
AB  - Iron is a potent oxidant that can lead to the formation of genotoxic lipid
      peroxides. Ascorbic acid, which enhances dietary iron absorption, has been
      suggested to enhance the oxidant effects of iron and to directly lead to the
      formation of lipid peroxides. The combined effects of dietary iron and ascorbic
      acid on genotoxicity were investigated by measuring the frequency of micronuclei
      in the bone marrow cells of C3H/He mice. In addition, liver iron concentration
      was measured in all treated groups. Three weeks old mice were fed diets for 3
      weeks containing iron at 100 or 300 mg/kg diet in the form of FeSO(4) that were
      supplemented either with or without ascorbic acid (15 g/kg diet). The results of
      the bone marrow micronucleus test revealed that the high iron diet resulted in an
      increased frequency of micronucleated polychromatic erythrocytes (MnPCEs) as
      compared to low iron. Ascorbic acid supplementation in the low iron diet did not
      show any effect on incidence of MnPCEs and protected against the increased
      frequency of MnPCEs induced by the high iron diet. However, liver iron
      concentration was significantly increased only in the high iron treated and
      ascorbic acid supplemented group as compared to all other groups. These results
      demonstrate that ascorbic acid protects against the clastogenic effects of iron.

PMID- 14644359
TI  - Heat shock proteins hsp32 and hsp70 as biomarkers of an early response? In vitro
      induction of heat shock proteins after exposure of cell culture to carcinogenic
      compounds and their real mixtures.
AB  - Heat shock proteins (hsp) are a highly conserved group of proteins that are
      synthesized as a response to different forms of stress (heat, toxic chemicals,
      diseases, non-physiological pH changes). Because of their high sensitivity to
      changes in the environment, these proteins were suggested as possible early
      biomarkers of exposure in ecotoxicological studies. The purpose of the present
      study was to check the suitability of hsp 32 and hsp70 as biomarkers of in vitro
      exposure to environmentally relevant carcinogens: polycyclic aromatic
      hydrocarbons (PAHs), their nitro-derivates, aromatic amines, acrylonitrile (ACN)
      and the mixture of organic compounds adsorbed onto ambient airborne particles
      (extractable organic matter, EOM). The expression of hsp 32 and hsp70 was studied
      in human diploid lung fibroblasts (HEL cells) and human monocytic leukaemia cells
      (THP-1 cells) incubated in vitro with different concentrations of
      dibenzo[a,l]pyrene (DB[a,l]P), 1-nitropyrene, (NP), 4-aminobiphenyl (ABP), ACN
      and EOM for different periods of time. The incubation of cells with DB[a,l]P, NP,
      ABP and EOM did not result in increased levels of hsp 32 or hsp70, either in dose
      or time-dependent manner. ACN induced the expression of hsp 32 as well as hsp70
      in HEL and THP-1 cells, which probably reflects its ability to induce oxidative
      stress. We conclude that hsp 32 and hsp70 are not suitable biomarkers of an early
      exposure to PAHs, their nitro-derivates, aromatic amines or EOM under the
      conditions used.

PMID- 14644360
TI  - Induction of chromosome aberrations in cultured human lymphocytes treated with
      ethoxyquin.
AB  - The chromosomal aberration test was employed to investigate the effect in vitro
      of a known antioxidant and food preservative, ethoxyquin (EQ, 1,2-dihydro-6
      ethoxy-2,2,4-trimethylquinoline) on human chromosomes. The studies were
      undertaken because there are no published in vitro data on genotoxicity of EQ in
      mammalian cells and there are many reports pointing out that it may be harmful to
      animals and human beings. Lymphocytes obtained from three healthy donors were
      incubated with EQ (0.01-0.5mM) both with and without metabolic activation.
      Stability studies performed by HPLC analysis showed that EQ was stable under the
      conditions of the lymphocyte cultures. The results of the chromosome aberration
      assay showed that EQ induces chromosome aberrations: gaps and breaks as well as
      dicentrics and atypical translocation chromosomes.

PMID- 14644361
TI  - Sunless skin tanning with dihydroxyacetone delays broad-spectrum ultraviolet
      photocarcinogenesis in hairless mice.
AB  - Sunless tanning with dihydroxyacetone (DHA) is not considered to be a sunscreen
      although it does absorb parts of the ultraviolet (UV) spectrum. We investigated
      the protection with topical application of DHA against solar UV-induced skin
      carcinogenesis in lightly pigmented hairless hr/hr C3H/Tif mice. Broad-spectrum
      UV radiation, simulating the UV part of the solar spectrum was obtained from one
      Philips TL12 and five Bellarium-S SA-1-12 tubes. Three groups of mice were UV
      exposed four times a week to a dose-equivalent of four times the standard
      erythema dose (SED), without or with application of 5 or 20% DHA only twice a
      week. Similarly, three groups of mice were treated with DHA and irradiated with a
      high UV dose (8 SED), simulating a skin burn. Two groups (controls) were not
      irradiated, but either left untreated or treated with 20% DHA alone. The UV
      induced skin pigmentation by melanogenesis could easily be distinguished from DHA
      induced browning and was measured by a non-invasive, semi-quantitative method.
      Application of 20% DHA reduced by 63% the pigmentation produced by 4 SED,
      however, only by 28% the pigmentation produced by 8 SED. Furthermore, topical
      application of 20% DHA significantly delayed the time to appearance of the first
      tumor >or=1mm (P=0.0012) and the time to appearance of the third tumor (P=2 x 10(
      6)) in mice irradiated with 4 SED. However, 20% DHA did not delay tumor
      development in mice irradiated with 8 SED. Application of 5% DHA did not
      influence pigmentation or photocarcinogenesis. In conclusion, this is the first
      study to show that the superficial skin coloring generated by frequent topical
      application of DHA in high concentrations may delay skin cancer development in
      hairless mice irradiated with moderate UV doses.

PMID- 14644362
TI  - Nicotine is not clastogenic at doses of 1 or 2 mg/kg body weight given orally to
      male mice.
AB  - Nicotine has been tested in the conventional mouse bone marrow assay. Single
      doses of 1mg/kg bw or 2mg/kg bw were given by oral intubations and bone marrow
      was sampled at 24h (1mg/kg) or at 6, 12 and 18 h after treatment (2mg/kg).
      Nicotine treatment did not increase the micronucleus frequencies in polychromatic
      erythrocytes while the positive control compound mitomycin C yielded the expected
      result. These data contradict the only published in vivo study of nicotine in
      which 1.1mg/kg bw was called positive for the induction of chromosomal
      aberrations in mouse bone marrow cells at all sampling intervals, even as early
      as 6h after treatment. It is discussed that aberration scoring is a matter of
      subjectivity and depends on strict discrimination criteria between gaps and true
      DNA discontinuities, i.e. breaks. International collaboration has shown that
      micronucleus scoring is less subjective, hence more reliable. Therefore it is
      concluded that nicotine is not clastogenic at the doses and time intervals tested
      in the present experiments.

PMID- 14644363
TI  - [Blood transfusion in emergency: importance of clear definitions].

PMID- 14644364
TI  - [To re-examine the methods of the continuous medical training and to evaluate
      them].

PMID- 14644365
TI  - [Endocarditis prophylaxis: ten years later].

PMID- 14644366
TI  - [Delayed evaluation of continuous medical education].
AB  - OBJECTIVES: To analyse the results of delayed evaluation of European teaching
      sessions using a questionnaire provided by the French College of
      Anaesthesiologists. STUDY DESIGN: Open evaluation. MATERIAL: Questionnaires were
      completed 3-6 months after European courses provided in November-December 1999.
      METHOD: The types of professional exercise and the medical practice as well as
      the theme of the courses were pointed out. The evaluation included six items
      noted from 1 to 10: usefulness of the abstract book, discussion with colleagues,
      discussion with a manager, decision to modify medical practice, application of
      that decision, own objectives fulfilled. The global mean score for each item was
      calculated. Results were compared according to the professional mode of exercise
      and the theme of the course. RESULTS: 5/7 centres provided information. 91/239
      questionnaires were returned to the organizers. The participants were working in
      different structures (private clinic: 25, university hospital: 31, general
      hospital: 27, PSPH: 8). The main exercise was anaesthesiology (75/77 answers).
      Means scores affected to the different items were around 7 for all but one of
      them. The mean score concerning discussion with a manager was significantly
      decreased to 3.5 +/- 3.2. Decision to modify their own practise was higher in
      private clinics compared to PSPH. The abstract book was more consulted after the
      first course (respiration and thorax). CONCLUSION: 3-6 months following the FEEA
      courses the participants thought to have fulfil their objectives and declared to
      have modify their medical practise. The lack of discussion with a manager should
      be analysed.

PMID- 14644367
TI  - [Obstetrical analgesia and anaesthesia in multiple sclerosis].
AB  - OBJECTIVES: The use of epidural analgesia and anaesthesia is controversial in
      patients with multiple sclerosis (MS) due to the potential neurotoxicity of local
      anaesthetics. The aim of this study was to evaluate the place and the safety of
      epidural obstetrical analgesia in these patients. PATIENTS AND METHODS: A
      consecutive series of 19 patients with MS was studied over 4 years, recording the
      type of anaesthesia and the obstetric and neurologic observations during the
      pregnancy and post-partum. RESULTS: Ten patients had epidural analgesia. One
      patient had a caesarean section under epidural anaesthesia. Five patients
      relapsed during the post-partum period. Only one of them had an epidural for a
      spontaneous vaginal delivery, without any evidence of a causal relationship.
      Spinal anaesthesia is generally not advocated in the presence of MS due to
      concerns relating to the stronger local anaesthetics required and was therefore
      not used. CONCLUSION: The results confirm that epidural analgesia is innocuous in
      this context. The important points are the precise evaluation of the existing
      neurological symptoms and the sparing of local anaesthetics thanks to the
      addition of opioids.

PMID- 14644368
TI  - [Risk factors for eclampsia: a case-control study].
AB  - OBJECTIVE: Our purpose was to characterize the risk factors of eclampsia in women
      with preeclampsia. PATIENTS AND METHODS: A case-control study was conducted at
      Monastir hospital to investigate risk factors for eclampsia between 1st January
      1995 and 30th June 2000. Cases were matched to preeclamptic controls on a 2:1
      ratio. Univariate analysis was used to determine which of the independent
      variables were significantly different between the groups. Those with significant
      differences were then entered into multiple logistic regression analysis to
      determine the characteristics that were independently related to eclampsia.
      RESULT: A total of 41 cases of eclampsia were ascertained from deliveries. The
      ratio of eclampsia cases to number of deliveries over the study period was 1.87
      per 1000. The first seizures occurred at home in 59% of the cases. Univariate
      analysis revealed statistical significance for the following variables associated
      with eclampsia: systolic hypertension > or =160 mmHg and diastolic > or =110
      mmHg, headache, visual symptoms, vivid deep tendon reflexes, proteinuria >3+ or
      >3 g d(-1), uric acid concentration > or =350 micromol l(-1), serum creatinine
      concentration >100 micromol l(-1) and aminotransferase aspartate >30 IU l(-1). A
      history of abortion appears to be the protective factor against eclampsia.
      However, with subsequent multivariate analysis, only vivid deep tendon reflexes
      and elevated uric acid concentration remained significant. CONCLUSION: These data
      indicate a need for improved prenatal care and medical attention focused on
      prodroms of eclampsia as well as the detection of preeclampsia to reduce the
      incidence of eclampsia.

PMID- 14644369
TI  - [Direct and indirect effects of epoietin alpha in an experimental model of
      thrombosis and bleeding in the rabbit].
AB  - OBJECTIVES: To study direct and indirect effects of EPO on haemostasis. STUDY
      DESIGN: Experimental, randomised. ANIMALS: Forty-eight New Zealand rabbits.
      METHOD: Animals were anaesthetised, ventilated and monitored continuously for
      blood pressure, heart rate, body temperature, and carotid blood flow variations
      and were randomised into four groups: control, EPO bolus 2400 IU kg(-1),
      fractionated EPO (one injection a week of 600 IU kg(-1) for 4 weeks), homologous
      red blood cell transfusion to reach the Ht level of the fractionated EPO group. A
      compression injury and a 75% stenosis of the carotid artery triggered a series of
      cyclic flow reductions (CFRs). CFRs were observed for a 20 min period in each
      group. Ear immersion bleeding time (BT) and hepato-splenic bleeding were
      performed at the end of the experiment. Biology was performed at the end of the
      thrombosis period: blood cells count, Hte, activated partial thromboplastin time,
      fibrinogen, arachidonic-induced platelet aggregation, EPO dosages. RESULTS: No
      significant increase in thrombosis (CFRs) in the two EPO groups and in the
      transfused group. Increase in Hte in the fractionated EPO group versus control.
      Group EPO bolus: decrease in BT and hepato-splenic bleeding versus control;
      decrease in hepato-splenic bleeding versus fractionated EPO group, increase in
      platelet aggregation velocity versus control. CONCLUSION: EPO did not increase
      the thrombotic risk in this rabbit model. EPO bolus decreased BT and hepato
      splenic bleeding.

PMID- 14644370
TI  - [Phoning study about postoperative practice and application of non-invasive
      ventilation].
AB  - OBJECTIVES: Incidence and management of positive pressure non-invasive
      ventilation (NIV) in intensive care unit (ICU) in the postoperative period. STUDY
      DESIGN: Phoning study performed on September 2001 in 60 ICU of south of France
      (public: 47, private: 13, medical: 11, surgical: 20, medical-surgical: 29), which
      were randomized from a national list. RESULTS: NIV was used currently on 55% and
      casually on 35% of the units. Ten percent of ICU, which never use NIV, were
      surgical on 83% with a lower number of bed (7 +/- 3 vs. 12 +/- 5). The most often
      humidification device used was a Heat and Moisture Exchanger (HME) (52%), a
      Heated Humidifier (HH) (26%), either (4%) and none device (19%). ICU that never
      used a humidification device used a home ventilator in 30%. Ventilators used were
      more often heavy ICU ventilators (80%) with a facial mask (89%). NIV was
      performed exclusively by physicians in 15% of cases and in collaboration after
      the first application in 71% of cases. Sixty-nine % of intensivists used NIV as a
      first choice for the treatment of acute postoperative respiratory failure and 54%
      of intensivists for the treatment of postoperative atelectasis. CONCLUSION: Use
      of NIV increases in ICU, particularly in surgical units. Practices are different
      between ICU. An HME is the most frequently humidification device used.

PMID- 14644371
TI  - [Anatomic and physiologic features of upper airways in children].
AB  - Anatomy of the upper aerodigestive tract in neonates and young children depends
      on the craniofacial growth. Skull base forms an horizontal line at birth. This
      line becomes concave inferiorly during the growth. This feature explains the high
      position of the larynx and its close proximity with the inferior edge of the soft
      palate. This gives a medial nasopharyngolaryngeal airway and two lateral
      digestive oropharyngeal ways. During the first years young children have a
      predominant nasal breath. Knowledge of the position, the conformation and the
      axial inferior and anterior obliquity of the larynx does facilitate its
      visualisation during laryngoscopy or intubation. The narrowness of the nasal
      cavities in neonates must be analysed in taking care of suprahyoid dyspnea in a
      neonate.

PMID- 14644372
TI  - [Choosing an endotracheal intubation set in paediatric anaesthesia].
AB  - The differences between a child's airway and an adult's, dictate differences in
      anaesthetic management techniques. Techniques and principles to assist in this
      management are reviewed in this article. Paediatric specificities of airway
      devices and other materials required for endotracheal intubation are described.
      In addition, recent development of equipment and current trends in management of
      paediatric airway are discussed.

PMID- 14644373
TI  - [Pulmonary embolism to the rescue in cardiac tamponade].
AB  - The association of cardiac tamponade and pulmonary embolism has not previously
      been described. We report the case of a patient, who presented with such an
      association, due to an underlying pulmonary carcinoma. When a major pericardial
      effusion is associated with pulmonary hypertension, some echocardiographic signs
      of tamponade may appear, such as a moderate right ventricular collapse, or the
      absence of a paradoxical septum. The presence of pulmonary hypertension in this
      context of tamponade may have paradoxically saved the life of this patient.

PMID- 14644374
TI  - [Acute colonic pseudo-obstruction (Ogilvie's syndrome) in pneumococcal meningo
      encephalitis treated with neostigmine].
AB  - We report the case of a 71-year-old man with acute colonic pseudo-obstruction
      that complicates a pneumococcal meningo-encephalitis. After 48 h of conservative
      management with nothing by mouth, nasogastric suction, fluid and electrolyte
      correction, withdrawal of any anticholinergic agents, a pharmacological approach
      with 2 mg of neostigmine was successful in intensive care unit. This treatment
      was effective in over 80% of patients of recent reports. Neostigmine might be
      considered as first-line therapy in patients who do not have major
      contraindications to its use, because of less frequent iatrogenic risk than
      colonoscopic decompression or surgery.

PMID- 14644375
TI  - [The industrial management and the management of surgical units].
AB  - Management of operating rooms is moving nowadays. Financial constraints as well
      as new operating practices prompt the hospital manager to optimise the operating
      room utilisation. The manufacturing systems faced a similar situation in the
      early 1980, due to the increase in the cost of the energetic products and the new
      competitive environment. Manufacturers had to improve dramatically their
      management capabilities in order to overcome their financial and technical
      difficulties. If the manufacturing management is extensively developed nowadays,
      the operating room is still running on an intuitive, individual and manual basis.
      The purpose of this review is to describe the main features of the manufacturing
      management and to identify those relevant to the management of operating rooms.

PMID- 14644377
TI  - [Septic shock due to tropical pyomyositis].

PMID- 14644376
TI  - [Continuous lumbar plexus block sets in France. Our experience].
AB  - The undeniable postoperative analgesia brought by the lumbar plexus block among
      patients scheduled for major surgery of the hip or knee justifies, the setting of
      a catheter to allow a continues analgesia more durable. Having drawn aside the
      difficulties of the daily practice (in allusion to the number of blocks carried
      out per day) and anatomical variations, the failure of the perineural catheter
      setting is in direct relationship with the material used by the
      anaesthesiologists for neurostimulation. The presentation of a case report
      describes a failure of catheter introduction due to the canula in deep continuous
      blocks, and the advantages and disadvantages of the various sets of
      neurostimulation. The authors conclude that the sets with the "catheter through
      the needle" are to be recommended, particularly the stimulating Tuohy needle.

PMID- 14644378
TI  - [Pulmonary oedema following postoperative bilateral paralysis of recurrent
      nerves].

PMID- 14644379
TI  - [Can we prove a septum existence of epidural space?].

PMID- 14644380
TI  - [Vegetative state: is the consciousness an arguable definition of life?].

PMID- 14644381
TI  - [Revision of the March 1992 consensus conference recommendations for the
      prophylaxis of infectious endocarditis].

PMID- 14644383
TI  - Dietary fats, carbohydrates and vascular disease: Sri Lankan perspectives.
AB  - The recent estimates for mortality from cardio and cerebrovascular diseases (CVD)
      for Sri Lanka--524 deaths per 100,000--is higher than that observed in many
      Western economies. However, neither an excessive total fat intake nor an increase
      in the more traditional plasma lipid markers, total and LDL cholesterol (LDL-c)
      levels may fully explain the increased vulnerability to CVD in this population.
      The average total fat intake of Sri Lankans is 25 percent of total energy (en%)
      and the reported total and LDL-c values are 4.9 and 2.5 mmol/l, respectively.
      With regard to the type of dietary fatty acids, the ratio of
      saturated/polyunsaturated fatty acids (PUFAs) in the average Sri Lankan diet is
      9/1 as compared with the current recommended ratio of <1/1. In spite of an
      adequate total fat intake (25 en%), the relatively low intake of PUFAs in
      association with a high carbohydrate diet (65 en%), appear to be resulting in
      similar metabolic outcomes to those of very low fat diets (VLFD, < 15 en% from
      fat), as reflected by high triglycerides and low HDL levels. Metabolic
      abnormalities including elevated postprandial hyperlipidemia, more atherogenic
      lipoprotein particles, hyperglycemia with resultant hyperinsulinemia and
      increased oxidative stress are likely to be more relevant in such settings. The
      application of novel biomarkers for example, lipoprotein measurements in the
      postprandial state, LDL particle size, estimates of endothelial dysfunction,
      soluble markers of inflammation and coagulability status may provide further
      insight into cardiovascular disease states in populations where the dietary
      matrix represents high intakes of highly digestible carbohydrates and saturated
      fat.

PMID- 14644384
TI  - Soy proteins reduce progression of a focal lesion and lipoprotein oxidiability in
      rabbits fed a cholesterol-rich diet.
AB  - The effects of different dietary proteins on the progression of a focal
      atheromatous lesion and on lipoprotein oxidiability were studied in male New
      Zealand rabbits. Focal lesions were induced on common carotid arteries by
      applying an electric current, using a bipolar microcoagulator. After surgery,
      animals were fed for 90 days two different diets, both with 1% cholesterol, 15%
      saturated fatty acids and 20% protein: the protein source was constituted in one
      group (SOY) by 16% soy protein isolate plus 4% milk whey proteins, in the other
      (CASEIN) by 16% casein plus 4% milk whey proteins. Lower levels of plasma
      cholesterol and triglycerides (-47 and -65%, respectively) (P < 0.05) were
      detected in the SOY versus the CASEIN group at the end of treatment. Cryosection
      analyses of the carotids, indicated a highly significant reduction (-39%; P <
      0.05) in the focal lesion progression in the SOY versus the CASEIN group. Copper
      mediated oxidation of low-density lipoprotein (LDL) from rabbits fed the two
      different diets, performed in vitro by analysis of conjugated diene formation,
      showed a significantly longer lag phase in the SOY (150 +/- 5 min) versus the
      CASEIN animals (20 +/- 3 min) (P < 0.05). These data, while confirming the well
      known lipid lowering properties of soy proteins, indicate, in this animal model,
      a remarkable activity on a focal atheromatous lesion, possibly also linked to a
      powerful antioxidant activity.

PMID- 14644386
TI  - Effects of 3-deazaadenosine on homocysteine and atherosclerosis in apolipoprotein
      E-deficient mice.
AB  - OBJECTIVE: In the past decade, elevated homocysteine concentration has achieved
      widespread recognition as an independent risk factor in the development of
      atherosclerosis. 3-Deazaadenosine (c3Ado) is a potent inhibitor and substrate for
      S-adenosylhomocysteine hydrolase and therefore may reduce homocysteine
      concentrations. The current study investigated the effect of c3Ado on serum
      homocysteine, atherosclerotic lesions, and the expression of adhesion molecules
      in apoE-knockout mice. METHODS AND RESULTS: Animals were placed on an atherogenic
      diet with or without c3Ado for 12 and 24 weeks. Frozen cross-sections of the
      aortic sinus and the proximal aorta were analyzed by computer-aided planimetry
      for fatty plaque formation. Macrophages, VCAM-1 and ICAM-1 were quantified by
      immunhistochemistry and oligo-cell reverse transcription polymerase chain
      reaction after laser microdissection. Application of c3Ado resulted in
      significant reduction of homocysteine levels by 35.9 and 45.3% after 12 and 24
      weeks, respectively (P < 0.001). Neointimal area and atherosclerotic plaque
      formation were significantly reduced in animals treated with c3Ado (P < 0.01).
      Moreover, monocyte adhesion and concomitant ICAM-1 and VCAM-1 antigen and RNA
      expression on the endothelial layer were significantly reduced (P < 0.001, P <
      0.01). CONCLUSION: Our results demonstrate that c3Ado induces a marked reduction
      of homocysteine concentrations which might explain in part the anti-atherogenic
      effect of the drug.

PMID- 14644385
TI  - Time course of vascular reactivity to contracting and relaxing agents after
      endothelial denudation by balloon angioplasty in rat carotid artery.
AB  - Endothelial injuries induced by different stimuli lead to proliferation of
      intimal vascular smooth muscle cells with formation of neointima. In this
      functional study, we evaluated the reactivity to contracting and vasorelaxing
      agents in Wistar rat carotid artery at different times (1, 7, 14, 21 and 28 days)
      after endothelial denudation with angioplastic balloon technique. Injured (IC)
      and uninjured carotid artery rings (UC) were placed in an isolated organ bath for
      isometric force displacement. IC collected at 1, 7, 14, 21 and 28 days showed a
      reduction in contraction to phenylephrine (0.3 microM), angiotensin II (0.1
      microM), U46619 (0.1 microM), KCl (60 mM) and A23187 (1microM) at any
      experimental time compared to rings obtained from UC. The evaluation of
      endothelial-derived relaxing or hyperpolarizing factor (EDRF or EDHF), induced by
      acetylcholine (0.001-1 microM) in presence of indomethacin (10 microM) or
      indomethacin and Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) (10
      and 100 microM, respectively), was carried out at 14, 21 and 28 days. The EDRF
      induced relaxation was significantly (P < 0.0001) reduced at 14 days and it
      improved through out the observation time, indeed at 28 days it was
      indistinguishable from UC relaxation curve. In contrast, the EDHF-induced
      relaxation was significantly (P < 0.0001) reduced at all experimental time. A
      significant reduction in nitric oxide-induced relaxation, sodium nitroprusside
      (0.001-10 microM), was observed at 7, 14 and 21 days, but not at 28 days. The
      relaxation induced by diazoxide (3-300 microM), an opener of KATP channels, was
      significantly reduced only at 7 days but not at 14, 21 and 28 days. Western blot
      analysis of myosin heavy chain revealed that up to 28 days the re-differentiation
      (maturity state) of smooth muscle cells was not yet reached. In conclusion, our
      data showed that hyporeactivity to contracting and relaxing agents in endothelial
      denuded carotid of rats could be linked to a multifactorial condition in which
      reduction of receptors and alterations in post-receptor transductions in
      neointima may produce modification of protein expression and/or variation in ion
      flux where calcium could have a pivotal role.

PMID- 14644387
TI  - Chylomicron remnants induce monocyte chemoattractant protein-1 expression via p38
      MAPK activation in vascular smooth muscle cells.
AB  - Chylomicron remnants, major lipoproteins at postprandial hyperlipidemia, have
      been considered to be proatherogenic lipoproteins. However, the mechanisms by
      which chylomicron remnants enhance atherosclerosis have not been fully
      understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which
      stimulates migration of monocytes and plays a critical role in the development of
      atherosclerosis. In this study, we investigated the effect of chylomicron
      remnants on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs). We
      prepared chylomicrons from the lymph of gastrostomized rats fed with egg solution
      and obtained chylomicron remnants from the plasma of hepatectomized rats which
      were injected with chylomicrons. Treatment of VSMC with chylomicron remnants
      resulted in a significant increase of the expression of MCP-1 mRNA and protein in
      a time-and a dose-dependent manner. Further, chylomicron remnants activated p38
      mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase
      (ERK1/2). Pretreatment of VSMCs with p38 MAPK inhibitors, SB203580 and SB202190,
      resulted in a dose-dependent inhibition of chylomicron remnants-induced MCP-1
      mRNA and protein expression, whereas a MAPK kinase inhibitor, PD98059, had no
      effect on these responses. MCP-1 secretion by chylomicron remnants was much more
      pronounced than those by chylomicrons, oxidized low-density lipoproteins, or
      lysophosphatidylcholine. These results indicated that chylomicron remnants
      stimulated MCP-1 expression in VSMCs, and suggested that chylomicron remnants
      might contribute to the formation of atherosclerosis through this proinflammatory
      effect.

PMID- 14644388
TI  - SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT)
      inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs.
AB  - Male Hartley guinea pigs were randomly allocated to one of four treatments, 10
      guinea pigs per group, for 12 weeks. The control diet contained no ASBT inhibitor
      (ASBTi) or simvastatin. Low ASBTi (LowASBTi) and high ASBTi (HighASBTi) were
      monotherapies containing 0.03 g/100 g and 0.1 g/100 g of the ASBTi SC-435.
      Combination therapy (COMBO) was a combination therapy consisting of 0.03 g/100 g
      ASBTi and 0.05 g/100 g simvastatin. Based on food consumption, guinea pigs
      received 17.2 and 47.8 mg/kg per day ASBTi in the ASBTi groups or 13.7 mg/kg per
      day ASBTi and 21.4 mg/kg per day simvastatin in the COMBO group. The amount of
      cholesterol in each diet was 0.25 g/100 g. LDL cholesterol was 40 and 70% lower
      with the HighASBTi and COMBO treatments compared to controls. Plasma
      triglycerides (TG) were 70% lower with COMBO therapy while HDL cholesterol was 43
      47% higher with all treatments. Hepatic free cholesterol was reduced 60-80% with
      all treatments. Cholesterol content in the aortic arch was reduced by 25 and 42%
      in the HighASBTi and COMBO groups. Fecal bile acids were increased by 2.5- and 4
      fold with HighASBTi and COMBO treatments. These data suggest that the
      interruption in the enterohepatic circulation of bile acids by ASBTi and statin
      co-administration therapy cause a significant reduction in plasma cholesterol
      concentrations and attenuate the progression of atherosclerosis in guinea pigs.

PMID- 14644389
TI  - The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages.
AB  - EN-RAGE is a ligand for the receptor for advanced glycation end products (RAGE)
      and may be involved in the development of diabetic macro- and micro-angiopathy.
      This study is designed to investigate the regulation of EN-RAGE gene expression
      in human macrophages. The amounts of EN-RAGE mRNA were measured in cultured human
      THP-1 macrophages after treatment with various stimuli known to modulate
      atherosclerosis. First, interleukin-6 (IL-6), a proinflammatory cytokine,
      increased the level of EN-RAGE mRNA by approximately 2-fold in a time- and a dose
      dependent fashion. EN-RAGE protein was detected in the cultured medium and
      increased significantly by the addition of IL-6. The induction was abolished by
      pretreatment with the JAK kinase inhibitor and cycloheximide, but not with the
      MEK kinase inhibitor. Second, pioglitazone (PIO), a thiazolidinedione, decreased
      the level of EN-RAGE mRNA by approximately 25% of the basal in a time- and a dose
      dependent fashion. Pioglitazone also inhibited the induction of EN-RAGE mRNA by
      IL-6. These results indicate the production of EN-RAGE is induced by IL-6 through
      de novo protein synthesis via the JAK-STAT kinase pathway and inhibited by the
      activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) in
      human macrophages.

PMID- 14644390
TI  - Oxidative damage to skeletal muscle following an acute bout of contractile
      claudication.
AB  - The purpose of this study was to determine the extent and sources of oxidative
      stress within skeletal muscle following an acute bout of contractile
      claudication. Twenty-four hours after unilateral ligation of the femoral artery,
      rat hind limbs were stimulated in vivo for 30 min, and force production measured.
      One-hour post-stimulation, animals were sacrificed and soleus and gastrocnemius
      muscles removed. There was significant reduction in force in the control limb
      (sham ligated/stimulated (SS)), while force in the ligated limb
      (ligated/stimulated (LS)) was reduced by 72%. There was an increase in skeletal
      muscle lipid hydroperoxides (53 and 47%) and protein carbonyls (57 and 54%) in
      the soleus and gastrocnemius muscles, respectively, and the muscle wet/dry weight
      ratio was increased in the gastrocnemius muscles. Total glutathione (GHS) was
      reduced, while xanthine oxidase (XO) activity and neutrophil levels were
      increased, in LS compared to SS in both soleus and gastrocnemius muscles. These
      data suggest that an acute bout of contractile claudication causes significant
      oxidative damage and edema to skeletal muscle. This is associated with both an
      increase in the activity of the radical-producing enzyme xanthine oxidase and an
      increase in activated neutrophils.

PMID- 14644391
TI  - High glucose induced NF-kappaB DNA-binding activity in HAEC is maintained under
      low shear stress but inhibited under high shear stress: role of nitric oxide.
AB  - In the present study, we investigated whether low shear (LS, 2 dyn/cm2) favors
      high glucose (HG, 30 mM) induced nuclear factor kappa B (NF-kappaB) activity by
      regulating NO release in human aortic endothelial cells (HAEC). The results show
      that (i) under LS, the NF-kappaB activity of HAEC exposed to HG was significantly
      higher than HAEC in normal glucose (NG, 5.5mM) (P < 0.05). In contrast, under HS,
      the activation of NF-kappaB in HAEC exposed to HG showed no significant
      difference compared to that of NG. (ii) The NF-kappaB activity induced by HG is
      suppressed by high shear (HS) in the absence of a NO synthase inhibitor, Nomega
      nitro-L-arginine methyl ester (L-NAME) but restored in its presence, while LS +
      HG induced NF-kappaB activity remains the same in the presence or absence of L
      NAME. (iii) Endothelial nitric oxide synthase (eNOS) protein expression and
      quantitative detection of NO indicated that high shear stress significantly
      induced higher eNOS expression and NO production compared to low shear stress
      condition. Collectively, these data suggest that HS exerts a protective effect on
      HG induced NF-kappaB activity through NO mediated signaling. LS, on the other
      hand, may down-regulate eNOS expression resulting in reduced NO release, and
      thereby maintain high glucose induced NF-kappaB DNA-binding activity. These
      observations explain, in part, the mechanism by means of which hyperglycemia
      accelerates the focal development of atherosclerotic lesions in low shear (lesion
      prone) areas of the arterial tree.

PMID- 14644392
TI  - Cytotoxic cellular cholesterol is selectively removed by apoA-I via ABCA1.
AB  - Excess intracellular free cholesterol (FC) is cytotoxic. This study examines
      prevention of FC-induced cytotoxicity in J774 macrophage foam cells by incubation
      with apolipoprotein AI (apoA-I). J774 were cholesterol enriched using acetylated
      low-density lipoprotein and FC/phospholipid (PL) dispersions. Treatment with an
      acyl coenzyme-A:cholesterol acyltransferase (ACAT) inhibitor, in the absence of
      extracellular acceptors, produced hydrolysis of stored esterified cholesterol
      (EC) and FC-induced cytotoxicity. Incubation of cells with ACAT inhibitor plus
      apoA-I resulted in FC efflux (0.39 +/- 0.02%/h) along with a reduction in
      cytotoxicity (26.30 +/- 5.80%), measured by adenine release. Small unilamellar
      vesicles (SUV) caused greater FC efflux (0.53 +/- 0.02%/h, P = 0.001), but a
      modest reduction in cytotoxicity (8.40 +/- 2.70%, P = 0.008). Co-incubation of
      ACAT inhibitor plus the cholesterol transport inhibitor U18666A or the
      antioxidant Probucol reduced efflux to apoA-I, but not to SUV. Pre-treatment of
      J774 foam cells with CTP-cAMP upregulates hormone sensitive lipase (HSL) and
      further upregulates ATP binding cassette A1 (ABCA1). Using mouse serum as a
      cholesterol acceptor, CTP-cAMP caused greater protection against FC-induced
      cytotoxicity compared to cells without pre-treatment, suggesting a role of ABCA1
      in removal of cytotoxic FC. We conclude that a cytotoxic pool of FC is located in
      the plasma membrane, is readily available for efflux to apoA-I, and removal of
      cytotoxic cholesterol may involve ABCA1.

PMID- 14644394
TI  - Skin tissue cholesterol (SkinTc) is related to angiographically-defined
      cardiovascular disease.
AB  - Parallel changes associated with aging found in the vasculature and skin at
      necropsy, have prompted small preliminary studies to assess the relation between
      skin tissue cholesterol (SkinTc) and cardiovascular disease. While these studies
      have been suggestive, no formal investigation is available to test this
      association. It would, therefore, be valuable to determine whether a relation
      between SkinTc and angiographic narrowing actually exists, the latter
      representing one accepted measurement of coronary atherosclerosis. METHODS:
      Patients at three hospitals undergoing coronary angiography and not on lipid
      altering agents (n = 649) were examined for skinTc using a non-invasive method.
      Vessels were evaluated manually (number with stenosis > or = 50%). Clinical
      characteristics, current medication use, and Framingham global risk score were
      recorded. RESULTS: SkinTc was significantly higher in patients with angiographic
      disease (124 +/- 30 vs. 118 +/- 30, P = 0.02). After adjustment for traditional
      coronary artery disease risk factors, SkinTc provided 7% additional risk (per 10
      SkinTc units) for angiographic disease. CONCLUSION: SkinTc, measured with a non
      invasive method, is associated with the presence of coronary artery disease as
      determined by catheterization. Such an assay may eventually help stratify patient
      risk and target prevention efforts.

PMID- 14644393
TI  - Phenotype-dependent and -independent actions of rosuvastatin on atherogenic
      lipoprotein subfractions in hyperlipidaemia.
AB  - This randomised, double-blind, placebo-controlled crossover study evaluated the
      effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B
      containing lipoprotein subfractions. Subjects, recruited based on raised plasma
      triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided
      into normotriglyceridaemic (NTG, n = 13; TG < 2.0 mmol/l) and
      hypertriglyceridaemic (HTG, n = 16; TG > or = 2.0 mmol/l) groups. Similar
      reductions on rosuvastatin were observed for both groups in LDL-C (NTG -60%; HTG 
      56%), apoB (both -49%), intermediate-density lipoprotein (NTG -57%; HTG -54%) and
      LDL circulating mass (NTG -52%, HTG -58%) (all P < 0.001 versus placebo), i.e.,
      these changes were phenotype independent. Phenotype dependency in response was
      observed in HTG relative to NTG in concentration of small dense LDL (LDL-III)
      (NTG -44%, P = NS; HTG -69%, P < 0.001), very-low-density lipoprotein1 (NTG -18%,
      P = NS; HTG 46%, P < 0.01), and remnant-like particle cholesterol (NTG -31%, P =
      NS; HTG -48%, P < 0.05). Rosuvastatin reduced cholesteryl ester transfer protein
      (CETP) by 33% in NTG and 37% in HTG (both P < 0.001); a reduction in cholesteryl
      ester transfer activity (-59%, P < 0.001) was observed in HTG only. Rosuvastatin
      therefore, in addition to lowering LDL and apoB-concentrations, largely corrected
      the TG and LDL abnormalities in subjects who had the propensity to develop the
      atherogenic lipoprotein phenotype.

PMID- 14644395
TI  - IL-1 cluster genes and occurrence of post-percutaneous transluminal coronary
      angioplasty restenosis: a prospective, angiography-based evaluation.
AB  - A polymorphic marker of the gene encoding the interleukin-1 (IL-1) receptor
      antagonist has been recently reported to be associated with risk of coronary
      artery disease. However, no prospective studies of the IL-1 gene cluster in
      relation to the occurrence of restenosis, a major complication of percutaneous
      transluminal coronary angioplasty (PTCA), have so far been conducted. We had the
      opportunity to investigate this question in a large, prospective cohort
      characterized by quantitative coronary angiography in all subjects. The IL1A
      A114S, IL1B -511C>T, IL1B 3953T>C, IL1RI exon1B T>C, and IL1RN VNTR (intron 2)
      polymorphisms were characterized in a cohort of 779 patients of whom 342
      ("cases") had developed restenosis (as defined by >50% loss of lumen compared to
      immediate post-procedure results) at repeat angiography at 6 months post-PTCA.
      All observed genotype frequencies were in Hardy-Weinberg equilibrium. Frequencies
      for the rare alleles were: IL1A S, 0.29 (cases), 0.28 (controls); IL1B T, 0.31
      (cases), and 0.33 (controls); IL1B C, 0.23 (cases), 0.24 (controls); IL1RI C,
      0.34 (cases), 0.35 (controls); and IL1RN 2, 0.29 (cases), 0.29 (controls),
      respectively. There was no evidence for an association between genotype and
      restenosis or degree of lumen loss (adjusted for covariables). Our data indicate
      that the common variants in the IL-1 cluster genes are not associated with
      incidence of restenosis after PTCA.

PMID- 14644396
TI  - Glutathione-S-transferase genotypes, smoking, and their association with markers
      of inflammation, hemostasis, and endothelial function: the atherosclerosis risk
      in communities (ARIC) study.
AB  - Recent epidemiologic studies suggest that polymorphisms of glutathione-S
      transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on
      risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous
      toxic compounds and products of oxidative stress, it is possible that GST
      genotypes may also modify the capacity of smoking to invoke a chronic
      inflammatory response. A cross-sectional analysis, using a subset of participants
      (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels
      of nine markers of inflammation, hemostasis, and endothelial function by
      different combinations of GST genotypes and cigarette smoking status.
      Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of
      smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor,
      ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other
      combinations of genotype and smoking. However, a formal test for interaction
      between GSTM1 genotype and smoking was statistically significant only for
      albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1
      1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and
      fibrinogen. The results of this study provide some limited evidence that GSTM1
      and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis,
      and endothelial function.

PMID- 14644398
TI  - Association of Chlamydia pneumoniae antibody with the cholesterol-lowering effect
      of statins.
AB  - To investigate the association between Chlamydia pneumoniae (C. pneumoniae)
      infection and atherosclerosis, we compared the effect of lipid-lowering drugs on
      carotid intima-media thickness (IMT) between patients who were positive and
      negative for C. pneumoniae antibodies. A total of 165 asymptomatic
      hypercholesterolemic patients were randomized to probucol (500 mg per day, n =
      82) or pravastatin (10 mg per day, n = 83) and followed for 2 years. The 2-year
      change of IMT in the common carotid artery was the primary endpoint, while mean
      IMT change and major cardiovascular events were secondary endpoints. C.
      pneumoniae antibodies (IgA and IgG) were measured by enzyme-linked immunosorbent
      assay. The 50 patients without C. pneumoniae antibodies showed significant
      reduction of IMT progression (-19%), while no significant change of IMT was noted
      in the 115 antibody-positive patients (-6%). Significant inverse associations
      were found between the reduction of IMT progression and the C. pneumoniae IgA-
      and IgG-antibody index (P < 0.01 and 0.01, respectively). No significant
      differences in the reduction of serum total-cholesterol and LDL-cholesterol were
      found between antibody-positive and -negative patients. There was no significant
      difference of efficacy between probucol and pravastatin. These observations
      suggest that C. pneumoniae infection reduces the effect of lipid-lowering therapy
      on carotid atherosclerosis and that this organism may play a role in the
      progression of atherosclerosis.

PMID- 14644397
TI  - Avasimibe, an ACAT inhibitor, enhances the lipid lowering effect of atorvastatin
      in subjects with homozygous familial hypercholesterolemia.
AB  - This study assessed the efficacy and safety of avasimibe (CI-1011), an inhibitor
      of acyl coenzyme A-cholesterol acyltransferase (ACAT) in subjects with homozygous
      familial hypercholesterolemia (HoFH). Twenty seven subjects were enrolled in a
      double-blind, randomized, 3-sequence crossover trial of atorvastatin 80 mg QD,
      avasimibe 750 mg QD, and the combined treatment of atorvastatin 80 mg QD and
      avasimibe 750 mg QD after a washout period of 4 weeks. Each treatment period was
      administered over 6 weeks for a total of 18 weeks. There were no significant
      lipid changes resulting from the administration of avasimibe monotherapy.
      Avasimibe in combination with atorvastatin resulted in a significantly better
      reduction of total cholesterol (TC) as compared to atorvastatin alone (-22%
      versus -18%) (P < 0.05). All other lipid changes were not statistically
      significant for combination therapy compared to atorvastatin monotherapy, however
      there were greater reductions in triglycerides (TG) (-24% versus -13%), low
      density lipoprotein cholesterol (LDL-C) (-23% versus -19%), very low-density
      lipoprotein cholesterol (VLDL-C) (-24% versus -13%) and high-density lipoprotein
      cholesterol (HDL-C) (-11% versus -6%). Avasimibe may modestly enhance the lipid
      reducing effect of atorvastatin by further inhibiting the production of
      intracellular cholesterol through mechanisms that appear to be compatible in this
      population.

PMID- 14644399
TI  - Enhanced efflux of cholesterol from ABCA1-expressing macrophages to serum from
      type IV hypertriglyceridemic subjects.
AB  - Since elevated plasma triglycerides (TGs) are an independent cardiovascular risk
      factor, we have compared the cholesterol efflux potential of sera from
      asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP)
      individuals using two different cell systems. In both type IIb and IV HTG, the
      efflux of cholesterol from SR-BI-rich Fu5AH cells was similar to that obtained
      with NLP. The maintenance of efflux efficiency in spite of reduced HDL
      cholesterol levels can be mainly attributed to the relative enrichment of HDL
      with phospholipid. In the J774 macrophage cell system, pretreatment with cAMP,
      which upregulates ABCA1, induced a markedly higher increase in efflux to type IV
      sera compared with type IIb or NLP. In addition, type IV sera exhibited two-fold
      higher pre-beta HDL relative concentration (percentage of total apo AI) compared
      with NLP. Moreover, positive correlations were established between ABCA1-mediated
      efflux and the serum pre-beta HDL levels or TG concentrations. Thus, the
      hyperTGemia is associated with a higher fraction of apo AI recovered as pre-beta
      HDL which appear to be partly responsible for enhanced efflux obtained upon the
      cAMP stimulation of J774 cells. In conclusion, we demonstrated for the first time
      that the ABCA1-expressing J774 cell system is responsive to the percent of apo AI
      present in human serum as pre-beta HDL. Our results suggest that high-plasma TG,
      accompanied by low HDL may not result in an impaired cholesterol efflux capacity.

PMID- 14644400
TI  - Carotid atherosclerosis in chronic renal failure-the central role of increased
      plaque burden.
AB  - Studies on carotid artery atherosclerosis have been performed in order to
      understand the high risk for cardiovascular disease in chronic renal failure
      (CRF). The purpose of this study was to evaluate the extent and nature of carotid
      artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52 +/-
      11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis
      treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58
      control subjects (CO) were examined. Common carotid artery intima-media thickness
      (IMT), plaque prevalence, plaque score, and stiffness index beta were determined.
      Furthermore, plaque calcification and internal carotid artery stenoses were
      classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P < 0.001) and
      plaque score (PR 3.3 +/- 4.3, DI 3.0 +/- 3.4, TR 2.5 +/- 3.2, CO 0.8 +/- 1.7 mm;
      P < 0.001) were significantly greater in the CRF patient groups compared to the
      controls, whereas no difference in IMT was noted between the study groups. The
      prevalences of plaque calcification and internal carotid artery stenoses were
      higher among the CRF patient groups. In addition, the stiffness index beta was
      higher in the CRF patient groups. The present study shows that the characteristic
      alterations of the carotid arteries in CRF include increased plaque burden,
      calcification and increased arterial stiffness.

PMID- 14644401
TI  - Insulin resistant young subjects at risk of accelerated atherosclerosis exhibit a
      marked reduction in peripheral endothelial function early in life but not
      differences in intima-media thickness.
AB  - Reduced bio-availability of nitric oxide leading to disturbed flow mediated
      (endothelial dependent) vasodilation (FMD) has been shown to be an early
      functional abnormality of the vascular system in insulin resistant individuals
      and other subjects at high risk for accelerated atherosclerosis. In addition, an
      increase of the intima-media thickness (IMT) is regarded as an early marker of
      morphological alterations of the vessel wall. Whether endothelial dysfunction
      (ED) is evident already at an early stage when morphological changes of the
      vessel wall are not apparent is still an open question. We, therefore, examined
      IMT and peripheral endothelial function in a group of young insulin resistant
      subjects in a cross-sectional study and compared these results with a
      metabolically healthy (insulin sensitive) control group. We measured IMT (distal
      common carotid arteries), endothelium-dependent and endothelium-independent
      vasodilation (flow mediated and glyceroltrinitrate induced vasodilation of the
      brachial artery) non-invasively with high resolution ultrasound (13 MHz) in 91
      young normoglycemic subjects (40/51 M/F, median: 31 years, range 18-50 years).
      Insulin sensitivity was measured with a euglycemic, hyperinsulinemic glucose
      clamp. Despite a marked reduction in flow-mediated vasodilation in insulin
      resistant (IR) subjects (FMD: median 3.4%, range -4.0 to 12.5 in IR versus 6.6%,
      range -1.2 to 20.1% in insulin sensitive subjects; P = 0.017), there was no
      difference in endothelial independent vasodilation (16.3%, range 5.7-41.0% versus
      16.1%, range 0.5-39.2%) and in IMT (0.50 mm, range 0.39-0.66 and 0.51, 0.40-0.70
      mm, respectively). These data suggest that ED can be detected very early in the
      life of insulin resistant subjects whereas no significant structural changes,
      indicated by a thickening of the intima-media layer, could be found. We therefore
      conclude that for identification of subjects with a high risk for accelerated
      atherosclerosis at an early stage, measurement of flow mediated vasodilation of
      the brachial artery may be more helpful than measuring thickness of the vascular
      wall.

PMID- 14644402
TI  - Heterozygosity for ABCA1 gene mutations: effects on enzymes, apolipoproteins and
      lipoprotein particle size.
AB  - A cohort of 13 female and 14 male heterozygotes for ATP binding cassette A1
      (ABCA1) gene defects was directly compared with 13 and 14 unaffected female and
      male family members of almost exact same age. The activities of three proteins
      that play key roles in HDL metabolism were measured in addition to extensive
      lipid and (apo) lipoprotein subfraction analysis. Compared to controls, LCAT
      activity was reduced by 15% in affected subjects (P < 0.001) while PLTP activity
      was unaffected. Interestingly, CETP activity was elevated by 50% in the
      heterozygote siblings of one kindred but was unaffected in heterozygotes of the
      three other families. With respect to lipids, the heterozygotes had normal total
      cholesterol (TC), and LDL-cholesterol concentrations but presented with a trend
      towards increased triglyceride levels (13%; P = 0.08). HDL metabolism, by
      contrast, was severely affected as illustrated by 40% reductions in HDL
      cholesterol (P < 0.001) with concomitant reductions in apoAI (25%; P < 0.001)
      levels and in lipoprotein subfraction LpAI (28%; P < 0.001), LpAI:AII (24%;
      P=0.014), and LpCIII:nonB (34%; P < 0.001) concentrations. We furthermore
      observed reduced average HDL particle size (5%; P = 0.004; 16% in female and 3.6%
      in male) and reduced plasma apoCIII concentration (15%; P = 0.006) while apoAII,
      apoAIV, apoE and apoB levels were unchanged. In conclusion, heterozygosity for
      ABCA1 defects was associated with reduced LCAT activity in absence of effects on
      PLTP activity. Of special interest was our finding that the effects of
      compromised ABCA1 function on HDL were more pronounced in women than in men.

PMID- 14644403
TI  - High-sensitive C-reactive protein level and oxidative stress-related status in
      former athletes in relation to traditional cardiovascular risk factors.
AB  - OBJECTIVE: To analyze systemic and cellular oxidative stress-related indices as
      well as C-reactive protein level in former top-level athletes in relation to
      traditional cardiovascular risk factors. METHODS: A cross-sectional study was
      performed in 53 former male athletes and 25 sedentary controls (age range: 39-59
      years). We measured anthropometric factors (BMI, fat percentage, WHR), resting
      blood pressure (SBP, DBP), serum cholesterol (CHOL), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides
      (TG), total antioxidant status (TAS), oxidized LDL-C (oxLDL), diene conjugates
      (DC), glutathione redox status, high-sensitive C-reactive protein (hsCRP), and
      leisure-time physical activity. RESULTS: Physically active former athletes had
      significantly lower mean overweight (BMI, fat percentage, WHR), better spectrum
      of atherogenesis indicators (CHOL, HDL-C, TG, TG:HDL-C ratio) and lower oxidative
      stress (oxLDL, oxLDL:LDL-C ratio, DC) values than sedentary ex-athletes. No
      significant differences in these variables were found between the sedentary ex
      athletes and control group. Significant associations were found between physical
      activity (METs), SBP, DBP, hypertension, CHOL, HDL-C, TG, TG:HDL-C ratio, oxLDL,
      oxLDL:LDL-C ratio, DC and hsCRP. CONCLUSIONS: A physically active lifestyle is
      related to a lower cardiovascular disease (CVD) risk profile including a
      substantially lower systemic and cellular oxidative stress status as well as C
      reactive protein level in middle-aged men.

PMID- 14644404
TI  - Postprandial hyperlipidemia: another correlate of the "hypertriglyceridemic
      waist" phenotype in men.
AB  - Fasting hypertriglyceridemia has been reported to be predictive of an exaggerated
      triglyceride (TG) response to an oral fat load. Abdominal obesity has also been
      associated with postprandial hyperlipidemia. The objective of the present study
      was to quantify the contribution of abdominal obesity and fasting
      hypertriglyceridemia to the magnitude of postprandial lipemia. For that purpose,
      potential differences in postprandial TG-rich lipoprotein (TRL) levels were
      examined among men characterized by the absence/presence of the
      "hypertriglyceridemic waist" phenotype following a standardized breakfast with a
      high fat content (64% calories as fat). Sixty-nine men (mean age +/- S.D.: 45.1
      +/- 10.5 years) were classified according to waist girth (< 90 or >/ or = 90 cm)
      and fasting TG concentrations (< 2.0 or > or = 2.0 mmol/l). Subjects
      characterized by "hypertriglyceridemic waist" (waist > or = 90 cm and fasting TG
      > or = 2.0 mmol/l) showed the highest TRL-TG concentrations (P < 0.0001)
      throughout the entire postprandial period (8 h) as well as elevated
      concentrations of apolipoprotein (apo) B-48 and apo B-100 in all TRL fractions
      (large, medium and small) compared to subjects with low fasting TG levels who had
      waist girth values either above or below 90 cm. These higher postprandial TRL-TG
      levels among carriers of the "hypertriglyceridemic waist" phenotype also led to
      significantly greater postprandial TG-total area under the curve (AUC) in total
      TRLs resulting mainly from the increased concentrations of large- and medium
      sized TRLs. Furthermore, subjects characterized by the "hypertriglyceridemic
      waist" phenotype displayed higher fasting insulin concentrations and postprandial
      insulin AUC compared to men with low fasting plasma TG levels and low waist girth
      values. In conclusion, results of the present study indicate that postprandial
      hyperlipidemia is associated with the simultaneous presence of abdominal obesity
      and elevated fasting TG concentrations: a condition that we have described as the
      "hypertriglyceridemic waist" phenotype.

PMID- 14644405
TI  - Reduction of remnant lipoprotein cholesterol concentrations by cilostazol in
      patients with intermittent claudication.
AB  - BACKGROUND: Elevated triglyceride-rich lipoproteins and reduced high-density
      lipoproteins (HDL) are associated with the development of intermittent
      claudication (IC), a life-limiting symptom of peripheral arterial disease.
      Cilostazol, a potent platelet inhibitor and vasodilator, lowers triglycerides and
      increases HDL concentrations in addition to increasing walking distance in
      patients with intermittent claudication. However, the association of remnant
      lipoproteins (a more atherogenic subset of triglyceride-rich lipoproteins) and
      peripheral arterial disease and the effects of cilostazol on remnant lipoproteins
      have not been studied. METHODS AND RESULTS: We quantified plasma remnant
      lipoprotein concentrations using the remnant lipoprotein-cholesterol assay (RLP
      C). Patients with intermittent claudication (n = 415) had significantly higher
      remnant lipoprotein concentrations compared to reference subjects (n = 874; 0.31
      +/- 0.32 versus 0.24 +/- 0.17 mmol/l, P < 0.001) in addition to elevated total
      triglyceride (2.67 +/- 1.92 versus 1.92 +/- 1.24 mmol/l, P < 0.001) and reduced
      high-density lipoprotein (HDL) cholesterol concentrations (1.06 +/- 0.31 versus
      1.22 +/- 0.36 mmol/l, P < 0.001). Cilostazol treatment (100 mg, b.i.d.) in
      patients with intermittent claudication (n = 56) for 6 months resulted in 20%
      reduction of remnant lipoprotein-cholesterol (from 0.27 +/- 0.21 to 0.22 +/- 0.09
      mmol/l, P < 0.05) versus no significant change (from 0.26 +/- 0.17 to 0.27 +/-
      0.12 mmol/l) in the placebo group (n = 67). Cilostazol also reduced triglyceride
      concentrations significantly (from 2.32+/-1.46 to 1.79+/-0.72 mmol/l, P < 0.01,
      in the cilostazol group versus 2.38 +/- 1.39 to 2.25 +/- 1.19 mmol/l in the
      placebo group) and increased HDL cholesterol concentrations (from 1.06 +/- 0.23
      to 1.24 +/- 0.34 mmol/l, P < 0.001) in the cilostazol group versus no significant
      change (1.06 +/- 0.34 to 1.09 +/- 0.36 mmol/l) in the placebo group.
      Pentoxifylline (400 mg, t.i.d.) did not have any significant effects on lipid
      variables (n = 66). CONCLUSIONS: Remnant lipoprotein concentrations are
      significantly elevated in patients with intermittent claudication and can be
      reduced by cilostazol. Reduction of remnant lipoproteins may provide a long-term
      benefit to the patients with symptomatic peripheral arterial disease.

PMID- 14644406
TI  - Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding
      globulin (SHBG) in men and women: The HERITAGE Family Study.
AB  - We tested the hypothesis that androgen, estrogen, and sex hormone-binding
      globulin (SHBG) levels would be significantly related to post-heparin hepatic
      lipase (HL) and lipoprotein lipase (LPL) activities in a sample of Caucasian men
      (n = 233) and women (n = 235) aged 17-64 years from the HERITAGE Family Study.
      Body composition (hydrostatic weighing), abdominal adipose tissue distribution
      (computed tomography), plasma lipid-lipoprotein and hormone levels, and post
      heparin lipases activities were measured. HL activity was significantly higher in
      males, whereas LPL activity was higher in women (P < 0.005). In women only, HL
      activity was positively associated with body fat mass (r = 0.17, P < 0.05) and
      intra-abdominal adipose tissue area (r = 0.18, P < 0.05). Significant
      associations were also found between fasting insulin and LPL activity (r = -0.16,
      P < 0.05 and r = -0.18, P < 0.005) as well as HL activity (r = 0.22, P < 0.005,
      and r = 0.27, P < 0.0001) in men and women, respectively. A positive association
      between total testosterone and HL activity was noted in men (r = 0.13, P = 0.05).
      In women, plasma SHBG levels were negatively associated with HL activity (r = 
      0.48, P < 0.0001), and statistical adjustment for body fat mass, visceral adipose
      tissue area, and fasting insulin did not attenuate this correlation. In
      multivariate analyses with models including adiposity variables and measurements
      of the hormonal profile, insulin, and testosterone levels were both independent
      positive predictors of HL activity in men. In women, hormone use was a
      significant positive predictor, and SHBG level a strong negative predictor of HL
      activity, independent of plasma estradiol and testosterone concentrations.
      Fasting insulin was the only significant predictor of LPL activity in men
      (negative association), whereas menstrual status, fasting insulin (negative
      associations), and plasma SHBG levels (positive association) were all independent
      predictors of LPL activity in women. These results suggest that the postulated
      sensitivity of lipolytic enzymes to androgens and estrogens is reflected by a
      strong negative association between SHBG levels and HL, and a lower magnitude
      positive association of this hormonal parameter to LPL activity in women. These
      associations appear to be independent from concomitant variation in total
      adiposity or body fat distribution.

PMID- 14644407
TI  - Metabolic syndrome best defines the multivariate distribution of blood variables
      in postinfarction patients.
AB  - The hypothesis was tested that metabolic syndrome (MS) plays a leading role in
      approximating the multivariate distribution of thrombogenic and metabolic blood
      variables in a population of postinfarction patients. The multivariate
      statistical technique of factor analysis was used to determine blood variable
      clustering 2 months after myocardial infarction. Five clusters resulted in two
      separate independent factors, dyslipidemia and metabolic, reflecting MS and the
      remaining interpreted as cholesterol-lipoprotein, vascular-inflammatory, and
      coagulation. All five factors accounted for 55% of total variance with MS
      associated factors accounting for 20% and individual factor contributions as
      follows: 11.6, 8.6, 12.9, 11.9, and 9.6%, respectively. There were no
      interactions of metabolic variables with thrombogenic variables or CRP in any
      factor. Results of subgroup analysis in males and females and in patients on and
      not on statins were all similar to the total group. We conclude there is no
      interaction of variables of MS or cholesterol-lipoprotein factors with those of
      thrombogenic factors. This independence yields the potential for use of factors
      in evaluating CVD risk. Further, the importance of MS in this group of
      postinfarction patients is emphasized, as the largest contribution to total
      variance was from MS factors, meaning that these variables best approximate the
      original multivariate distribution.

PMID- 14644408
TI  - Interleukin-6 serum levels and genotypes influence the risk for myocardial
      infarction.
AB  - OBJECTIVE: Several studies show that the inflammatory component in
      atherosclerosis may contribute to increased risk for cardiovascular disease
      (CVD). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-stimulatory
      cytokine of presumed importance for CVD and the metabolic syndrome. METHODS AND
      RESULTS: In this case-control study, 1179 surviving myocardial infarction (MI)
      cases and 1528 healthy controls were genotyped for three IL-6 promoter SNPs, and
      serum concentrations of IL-6 and C-reactive protein (CRP) were measured. In men,
      MI risk assessed as odds ratios (OR) was higher with increasing IL-6 levels, with
      the highest compared to the lowest IL-6 quartiles giving an OR of 2.7 [95% CI 1.7
      4.4]. The ORs were independent from the effects of elevated CRP which were
      associated with modest MI risks (OR = 1.6 [95% CI 1.0-2.5]). Also, synergistic
      interactions between high IL-6 levels and hypercholesterolaemia further increased
      MI risk estimates. The -174C allele was associated with lower serum-insulin
      levels among male controls but did not significantly influence MI risk or IL-6
      levels. CONCLUSIONS: Elevated IL-6 levels are important risk markers for MI in
      men, the risk being further enhanced through synergistic interaction with
      hypercholesterolaemia. The data provide no clear evidence that polymorphisms in
      the IL-6 promotor region play a significant role in the pathogenesis of MI, and
      it remains to be further evaluated whether or not the -174C allele is of
      relevance for insulin resistance.

PMID- 14644409
TI  - Chylomicron remnants of various sizes are lowered more effectively by fenofibrate
      than by atorvastatin in patients with combined hyperlipidemia.
AB  - Both atorvastatin and fenofibrate are known to lower postprandial chylomicrons
      and chylomicron remnants. However, until now it has not been investigated which
      of the two drugs is more effective in one and the same patient and, secondly,
      whether these drugs exert different effects on chylomicron remnants of different
      sizes. To this end 12 patients with mixed hyperlipidemia were treated in a
      crossover study with 40 mg atorvastatin or with 200 mg micronized fenofibrate
      once daily for 6 weeks. Oral fat loading was given before and after each
      treatment. Chylomicron remnants of various sizes were determined by fluorometric
      determinations of retinyl palmitate after lipoprotein separation by size
      exclusion chromatography. As expected, atorvastatin was more effective than
      fenofibrate on total and LDL-cholesterol (P < 0.05). Fenofibrate, in contrast,
      was more effective on all triglyceride-rich lipoproteins in both the fasting and
      the postprandial state. The stronger effect of fenofibrate affected not only
      chylomicrons and VLDL but also chylomicron remnants. It reduced large chylomicron
      remnants by 66% at 6h and by 74% at 8 h. The action of atorvastatin was less
      pronounced, with corresponding reductions of 42 and 65% (P < 0.05 only after 8
      h). Fenofibrate was even more effective on small chylomicron remnants, yielding
      reductions of 47, 74, and 66% at 4, 6, and 8 h. Atorvastatin, in contrast, gave
      reductions of 30 and 26% after 6 and 8 h, the effect reaching statistical
      significance only after 6h. Fenofibrate is therefore more effective than
      atorvastatin in lowering all triglyceride-rich lipoproteins, including large and
      small chylomicron remnants.

PMID- 14644411
TI  - A European Research Council for all sciences: a dream that may come true.

PMID- 14644410
TI  - Red wine, resveratrol, Chlamydia pneumoniae and the French connection.

PMID- 14644412
TI  - Simultaneous activation of apoptosis and inflammation in pathogenesis of septic
      shock: a hypothesis.
AB  - Sepsis, a widely prevalent disease with increasing morbidity and mortality, is
      thought to result from uncontrolled inflammatory responses to microbial infection
      and/or components. However, failure of several experimental anti-inflammatory
      therapies has necessitated re-evaluation of the paradigm underlying the
      pathogenesis of this complex disorder. Apoptotic cell death forms a second
      dominant feature of septic shock in patients and animal models. Anti-apoptotic
      strategies may protect animals from septic death. However, simultaneous
      occurrence of apoptosis and inflammation is necessary for septic death. At the
      cellular level, apoptosis plays a central role in the development of the lymphoid
      system and regulation of immune responses. Immune activation renders cells
      refractory to apoptosis while apoptosis of activated lymphocytes is an important
      immunoregulatory mechanism. Factors such as complement factor 5a, caspase-1 and
      mitogen-activated protein kinase, which participate in apoptosis as well as pro
      inflammatory pathways, may be responsible for simultaneous activation of
      apoptosis and inflammation in sepsis. Further identification of other similar
      biochemical events capable of co-activating inflammation and apoptosis may
      provide new targets for therapy of this hitherto untreatable disease.

PMID- 14644413
TI  - The active site and mechanism of action of recombinant acetohydroxy acid synthase
      from tobacco.
AB  - Acetohydroxy acid synthase (AHAS) is one of several enzymes that require thiamine
      diphosphate and a divalent cation as essential cofactors. Recently, the three
      dimensional structure of the enzyme from yeast has been determined [Pang et al.,
      J. Mol. Biol. 317 (2002) 249-262]. While this structure sheds light on the
      binding of the cofactors and the reaction mechanism, the interactions between the
      substrates and the enzyme remain unclear. We have studied the pH dependence of
      kinetic parameters in order to obtain information about the chemical mechanism in
      the active site. Data are consistent with a mechanism in which substrate
      selectively catalyzed to the enzyme with an unprotonated base having a pK of
      6.48, and a protonated group having a pK of 8.25 for catalysis. The temperature
      dependence of kinetic parameters was pH-dependent, and the enthalpies of
      ionization, DeltaH(ion), calculated from the slope of pK(1) and pK(2) are both pH
      independent. The solvent perturbation of kinetic parameters was pH-dependent, and
      the pK(1) from the acidic side and the pK(2) from the basic side were shifted
      down 0.4 pH units and shifted up 0.6 units as water was replaced by 15% ethanol,
      respectively. The data are discussed in terms of the acid-base chemical
      mechanism.

PMID- 14644414
TI  - 1-Cys peroxiredoxin knock-out mice express mRNA but not protein for a highly
      related intronless gene.
AB  - 1-Cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin family with a
      single conserved cysteine, is a unique antioxidant enzyme. We have generated mice
      in which the 1-cysPrx gene has been inactivated; they are viable and fertile.
      Mice have a highly related intronless gene (1-cysPrx-P1, GenBank accession number
      AF085220) with the same length of open reading frame (224 aa) as 1-cysPrx but
      located on a different chromosome. Since the product of this gene possibly could
      mimic 1-cysPrx function, we compared expression of 1-cysPrx and 1-cysPrx-P1 in
      mouse tissues by real-time polymerase chain reaction and Western blot. 1-cysPrx
      mRNA and protein were expressed in all mouse tissues that were examined with the
      highest expression level in lung. 1-cysPrx-P1 mRNA was expressed only in testis.
      In the 1-cysPrx 'knock-out' mouse, 1-cysPrx-P1 mRNA expression level was similar
      to the wild type but protein expression was not detected. Thus, mouse 1-cysPrx-P1
      is an mRNA-expressed pseudogene that does not result in detectable protein in
      vivo.

PMID- 14644415
TI  - Ganglioside-dependent cell attachment and endocytosis of murine polyomavirus-like
      particles.
AB  - For murine polyomavirus (Py), previous studies suggest the cellular target is a
      terminal alpha2,3-linked sialic acid. Here, we investigate the binding and uptake
      of mouse polyomavirus-like particles (PyVLP) derived from bacterially expressed
      VP1. We find that in fibroblast 3T6 cells, binding of PyVLP was substantially
      reduced by sialidase treatment, but only moderately affected by protease
      treatment, suggesting glycolipids such as the sialic acid-containing gangliosides
      mediate cell attachment. We further tested the entry requirement of PyVLP using
      the ganglioside-deficient GM95 murine cell line, and find PyVLP binding and entry
      were reduced in these cells. Finally, we find that addition of gangliosides
      G(M1), G(D1a), and G(T1b) to GM95 cells restored cellular PyVLP binding and
      uptake. Taken together, results indicate that gangliosides function in PyVLP cell
      attachment and endocytosis.

PMID- 14644416
TI  - Transcriptional regulation of the human GM3 synthase (hST3Gal V) gene during
      monocytic differentiation of HL-60 cells.
AB  - We studied the transcriptional regulation of human GM3 synthase (hST3Gal V)
      during monocytic differentiation of HL-60 cells induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA). Northern blot and reverse transcription
      polymerase chain reaction indicated that the induction of hST3Gal V by TPA is
      regulated at the transcriptional level. To elucidate the mechanism underlying the
      regulation of hST3Gal V gene expression during the differentiation of HL-60 cells
      induced by TPA, we characterized the promoter region of the hST3Gal V gene.
      Functional analysis of the 5'-flanking region of the hST3Gal V gene by the
      transient expression method showed that the -177 to -83 region, which contains a
      cAMP responsive element binding protein (CREB) binding site at -143, functions as
      the TPA-inducible promoter in HL-60 cells. In addition, gel shift assays and site
      directed mutagenesis indicated that the CREB binding site at -143 is crucial for
      the TPA-induced expression of the hST3Gal V in HL-60 cells.

PMID- 14644417
TI  - The effects of post-translational processing on dystroglycan synthesis and
      trafficking.
AB  - Dystroglycan is a component of the dystrophin glycoprotein complex that is
      cleaved into two polypeptides by an unidentified protease. To determine the role
      of post-translational processing on dystroglycan synthesis and trafficking we
      expressed the dystroglycan precursor and mutants thereof in a heterologous
      system. A point mutant in the processing site, S655A, prevented proteolytic
      cleavage but had no effect upon the surface localisation of dystroglycan.
      Mutation of two N-linked glycosylation sites that flank the cleavage site
      inhibited proteolytic processing of the precursor. Furthermore, chemical
      inhibition of N- and O-linked glycosylation interfered with the processing of the
      precursor and reduced the levels of dystroglycan at the cell surface.
      Dystroglycan processing was also inhibited by the proteasome inhibitor
      lactacystin. N-linked glycosylation is a prerequisite for efficient proteolytic
      processing and cleavage and glycosylation are dispensable for cell surface
      targeting of dystroglycan.

PMID- 14644418
TI  - Involvement of Akt in mitochondria-dependent apoptosis induced by a cdc25
      phosphatase inhibitor naphthoquinone analog.
AB  - Vitamin K-related analogs induce growth inhibition via a cell cycle arrest
      through cdc25A phosphatase inhibition in various cancer cell lines. We report
      that 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (DDN), a naphthoquinone
      analog, induces mitochondria-dependent apoptosis in human promyelocytic leukemia
      HL-60 cells. DDN induced cytochrome c release, Bax translocation, cleavage of Bid
      and Bad, and activation of caspase-3, -8, -9 upon the induction of apoptosis.
      Cleavage of Bid, the caspase-8 substrate, was inhibited by the broad caspase
      inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), whereas cytochrome c
      release was not affected, suggesting that activation of caspase-8 and subsequent
      Bid cleavage occur downstream of cytochrome c release. DDN inhibited the
      activation of Akt detected by decreasing level of phosphorylation. Overexpression
      of constitutively active Akt protected cells from DDN-induced apoptosis, while
      dominant negative Akt moderately enhanced cell death. Furthermore, Akt prevented
      release of cytochrome c and cleavage of Bad in DDN-treated HL-60 cells. Taken
      together, DDN-induced apoptosis is associated with mitochondrial signaling which
      involves cytochrome c release via a mechanism inhibited by Akt.

PMID- 14644419
TI  - Regulation of flotillin-1 in the establishment of NIH-3T3 cell-cell interactions.
AB  - Flotillin-1 is a lipid raft-associated protein involved in neuronal regeneration,
      insulin signaling in adipocytes, and phagosome maturation in macrophages. We
      detected abundant flotillin-1 mRNA expression in confluent cultures of mouse NIH
      3T3 fibroblasts. These cells were used as a model to assess the regulation of
      flotillin-1 mRNA and protein expression by cell-cell interactions. The disruption
      of cell-cell interactions triggered the downregulation of the flotillin-1 gene.
      However, the establishment of new cell interactions, and finally confluence,
      increased both the flotillin-1 transcript and its protein. Despite flotillin-1
      having been described as an integral protein of the cell membrane, it is also
      very conspicuous in the hydrophilic fraction (the non-membrane fraction) of
      confluent cell extracts. The promoter region of the flotillin-1 gene was isolated
      and analyzed by transfection experiments, and the regulatory domains containing
      motifs for binding transcription factors involved in cell differentiation were
      identified.

PMID- 14644420
TI  - Outer membrane protein A of Escherichia coli forms temperature-sensitive channels
      in planar lipid bilayers.
AB  - The temperature dependence of single-channel conductance and open probability for
      outer membrane protein A (OmpA) of Escherichia coli were examined in planar lipid
      bilayers. OmpA formed two interconvertible conductance states, small channels, 36
      140 pS, between 15 and 37 degrees C, and large channels, 115-373 pS, between 21
      and 39 degrees C. Increasing temperatures had strong effects on open
      probabilities and on the ratio of large to small channels, particularly between
      22 and 34 degrees C, which effected sharp increases in average conductance. The
      data infer that OmpA is a flexible temperature-sensitive protein that exists as a
      small pore structure at lower temperatures, but refolds into a large pore at
      higher temperatures.

PMID- 14644421
TI  - Inflammatory prompts produce isoform-specific changes in the expression of
      leukotriene B(4) omega-hydroxylases in rat liver and kidney.
AB  - Cytochrome p450 (CYP) 4Fs metabolize leukotriene B(4) and other inflammatory
      mediators in the arachidonic acid cascade. Here we show that lipopolysaccharide
      (LPS) treatment suppresses CYP4F4 and up-regulates CYP4F5 mRNA expression in rat
      liver whereas renal CYP4Fs are essentially unchanged. BaSO(4) treatment, in
      contrast, increases both hepatic and renal CYP4F expression levels. Thus,
      distinct regulatory mechanisms in CYP4F expression might operate under different
      inflammatory prompts. To examine hepatic totipotency, primary hepatocytes were
      treated with varying doses of LPS resulting in decrease in all the CYP4F
      isoforms. Treatment of hepatocytes with 5 ng/ml of interleukin-1beta mimics the
      in vivo effects of LPS on CYP4F expression.

PMID- 14644422
TI  - Alternative splicing generates a novel non-secretable resistin isoform in Wistar
      rats.
AB  - Resistin is a secreted adipose tissue hormone that belongs to the resistin-like
      molecule family. We report here a new alternatively spliced isoform of the rat
      resistin gene, named S-resistin (short resistin), detected in adipose tissue by
      reverse transcription-polymerase chain reaction (RT-PCR). A comparison of this
      cDNA variant and genomic sequences indicates the lack of the second exon
      containing the secretory consensus signal. Both cDNAs, resistin and S-resistin,
      were carboxy-tagged with FLAG epitope and transiently expressed in cultured cell
      lines. While the resistin-FLAG construct gives the expected pattern for a
      secretion protein, the S-resistin-FLAG construct yielded a predominant nuclear
      staining. These results indicate that this splicing event regulates the fate and
      probably the function of the mature protein.

PMID- 14644423
TI  - Caenorhabditis elegans dna-2 is involved in DNA repair and is essential for germ
      line development.
AB  - Caenorhabditis elegans germ cell proliferation and development were severely
      damaged in second generation dna-2 homozygotes. Even in the first generation, a
      much higher incidence of aberrant chromosomes in oocytes and resultantly higher
      embryonic lethality were found vs. wild type, when DNA breaks were induced by
      gamma-rays or camptothecin. The deficiency of dna-2 in combination with RNA
      interference on mre-11 gene expression synergistically aggravated germ-line
      development, especially oocyte formation. These results suggest that C. elegans
      Dna-2 is involved in a DNA repair pathway paralleling homologous recombination or
      non-homologous end joining with mre-11 participation.

PMID- 14644424
TI  - Role of secretory and cytosolic phospholipase A(2) enzymes in
      lysophosphatidylcholine-stimulated monocyte arachidonic acid release.
AB  - To determine if lysophosphatidylcholine (lysoPC) is able to induce
      proinflammatory changes in monocytes, its ability to stimulate arachidonic acid
      (AA) release, a product of phospholipase A2 (PLA(2)) activity, has been analyzed.
      LysoPC increased AA release in THP-1 and Mono Mac6 cells in a time- and
      concentration-dependent manner. The monocytes expressed both secretory and
      cytosolic PLA(2) enzymes and AA release was strongly reduced by cellular
      pretreatment with different PLA(2) inhibitors and by pertussis toxin, an
      inhibitor of G(i)-protein activation. This indicates that both cytosolic and
      secretory PLA(2) enzymes regulate specific lysoPC receptor-induced AA release,
      suggesting lysoPC participation in monocyte proinflammatory activation.

PMID- 14644425
TI  - Mechanistic studies of the SufS-SufE cysteine desulfurase: evidence for sulfur
      transfer from SufS to SufE.
AB  - SufS is a cysteine desulfurase of the suf operon shown to be involved in iron
      sulfur cluster biosynthesis under iron limitation and oxidative stress
      conditions. The enzyme catalyzes the conversion of L-cysteine to L-alanine and
      sulfide through the intermediate formation of a protein-bound cysteine persulfide
      in the active site. SufE, another component of the suf operon, has been
      previously shown to bind tightly to SufS and to drastically stimulate its
      cysteine desulfurase activity. Working with Escherichia coli proteins, we here
      demonstrate that a conserved cysteine residue in SufE at position 51 is essential
      for the SufS/SufE cysteine desulfurase activity. Mass spectrometry has been used
      to demonstrate (i). the ability of SufE to bind sulfur atoms on its cysteine 51
      and (ii). the direct transfer of the sulfur atom from the cysteine persulfide of
      SufS to SufE. A reaction mechanism is proposed for this novel two-component
      cysteine desulfurase.

PMID- 14644426
TI  - Mouse polyomavirus large T antigen inhibits cell growth and alters cell and
      colony morphology in Saccharomyces cerevisiae.
AB  - The gene for mouse polyomavirus large tumor (LT) antigen, a potent oncoprotein,
      was expressed in Saccharomyces cerevisiae from the inducible GAL1 promoter.
      Substantial cell growth inhibition as well as colony and cell morphology changes
      dependent on cyclic adenosine monophosphate (cAMP) were observed. In contrast to
      cell and colony morphology alterations, the growth inhibition appeared to be
      transient, thus indicating the existence of an active adaptation of yeast cells
      to the LT antigen presence.

PMID- 14644427
TI  - Functional consequences of an in vivo mutation in exon 10 of the human GLUT1
      gene.
AB  - The functional consequences of an in vivo heterozygous insertion mutation in the
      human facilitated glucose transporter isoform 1 (GLUT1) gene were investigated.
      The resulting frameshift in exon 10 changed the primary structure of the C
      terminus from 42 in native GLUT1 to 61 amino acid residues in the mutant. Kinetic
      studies on a patient's erythrocytes were substantiated by expressing the mutant
      cDNA in Xenopus laevis oocytes. K(m) and V(max) values were clearly decreased
      explaining pathogenicity. Targeting to the plasma membrane was comparable between
      mutant and wild-type GLUT1. Transport inhibition by cytochalasin B was more
      effective in the mutant than in the wild-type transporter. The substrate
      specificity of GLUT1 remained unchanged.

PMID- 14644428
TI  - Distinctive binding and structural properties of piscine transthyretin.
AB  - The thyroid hormone binding protein transthyretin (TTR) forms a macromolecular
      complex with the retinol-specific carrier retinol binding protein (RBP) in the
      blood of higher vertebrates. Piscine TTR is shown here to exhibit high binding
      affinity for L-thyroxine and negligible affinity for RBP. The 1.56 A resolution X
      ray structure of sea bream TTR, compared with that of human TTR, reveals a high
      degree of conservation of the thyroid hormone binding sites. In contrast, some
      amino acid differences in discrete regions of sea bream TTR appear to be
      responsible for the lack of protein-protein recognition, providing evidence for
      the crucial role played by a limited number of residues in the interaction
      between RBP and TTR. Overall, this study makes it possible to draw conclusions on
      evolutionary relationships for RBPs and TTRs of phylogenetically distant
      vertebrates.

PMID- 14644429
TI  - The function of conserved cysteine residues in the extracellular domain of human
      receptor-activity-modifying protein.
AB  - The receptor-activity-modifying protein (RAMP) 1 is a single-transmembrane-domain
      protein associated with the calcitonin-like receptor (CLR) to reveal a calcitonin
      gene-related peptide (CGRP) receptor. The extracellular region of RAMP1 contains
      six conserved cysteines. Here, Cys(27) in myc-tagged human (h) RAMP1 was deleted
      (hRAMP1Delta1), and Cys(40), Cys(57), Cys(72), Cys(82) and Cys(104) were each
      replaced by Ala. In COS-7 cells expressing hCLR/myc-hRAMP1Delta1 or -C82A, cell
      surface expression, [(125)I]halphaCGRP binding and cAMP formation in response to
      halphaCGRP were similar to those of hCLR/myc-hRAMP1. Cell surface expression of
      myc-hRAMP1-C72A was reduced to 24+/-7% of myc-hRAMP1, and that of -C40A, -C57A
      and -C104A was below 10%. [(125)I]halphaCGRP binding of hCLR/myc-hRAMP1-C72A was
      13+/-3% of hCLR/myc-hRAMP1 and it was undetectable in hCLR/myc-hRAMP1-C40A-, 
      C57A- and -C104A-expressing cells. Maximal cAMP stimulation by halphaCGRP in
      hCLR/myc-hRAMP1-C40A- and -C72A-expressing cells was 14+/-1% and 33+/-2% of that
      of the hCLR/myc-hRAMP1 with comparable EC(50). But cAMP stimulation was abolished
      in cells expressing hCLR/myc-hRAMP1-C57A and -C104A. In conclusion, CGRP receptor
      function was not affected by the deletion of Cys(27) or the substitution of
      Cys(82) by Ala in hRAMP1, but it was impaired by the substitution of Cys(40),
      Cys(57), Cys(72) and Cys(104) by Ala. These four cysteines are required for the
      transport of hRAMP1 together with the CLR to the cell surface.

PMID- 14644430
TI  - Investigation of cytokinin-deficient phenotypes in Arabidopsis by ectopic
      expression of orchid DSCKX1.
AB  - The plant hormone cytokinin plays a major role in regulating plant growth and
      development. Here we generated cytokinin-reduction Arabidopsis plants by
      overexpressing a heterologous cytokinin oxidase gene DSCKX1 from Dendrobium
      orchid. These transgenic plants exhibited reduced biomass, rapid root growth,
      decreased ability to form roots in vitro, and reduced response to cytokinin in
      growing calli and roots. Furthermore, the expression of KNAT1, STM, and CycD3
      genes was significantly reduced in the transgenic plants, suggesting that
      cytokinin may function to control the cell cycles and shoot/root development via
      regulation of these genes.

PMID- 14644431
TI  - Structural basis of calcium and galactose recognition by the lectin PA-IL of
      Pseudomonas aeruginosa.
AB  - The structure of the tetrameric Pseudomonas aeruginosa lectin I (PA-IL) in
      complex with galactose and calcium was determined at 1.6 A resolution, and the
      native protein was solved at 2.4 A resolution. Each monomer adopts a beta
      sandwich fold with ligand binding site at the apex. All galactose hydroxyl
      groups, except O1, are involved in a hydrogen bond network with the protein and
      O3 and O4 also participate in the co-ordination of the calcium ion. The
      stereochemistry of calcium galactose binding is reminiscent of that observed in
      some animal C-type lectins. The structure of the complex provides a framework for
      future design of anti-bacterial compounds.

PMID- 14644432
TI  - p53 down-regulation: a new molecular mechanism involved in ischaemic
      preconditioning.
AB  - Ischaemic preconditioning is associated with the activation of prosurvival
      mechanisms. Here we demonstrate that following a preconditioning protocol, the
      proapoptotic p53 is inactivated possibly via phosphatidylinositol 3-kinase (PI3K)
      protein kinase B (Akt)-murine double minute 2 (Mdm2) phosphorylation. Our data
      show that in preconditioned hearts Mdm2 was significantly phosphorylated, and
      wortmannin (a PI3K inhibitor) abrogated this effect (Western blotting). Also in
      preconditioned hearts p53 was shown to be bound to phospho-Mdm2 (co
      immunoprecipitation). Furthermore, pifithrin alpha (a p53 inhibitor),
      administered to isolated perfused hearts prior to ischaemia, significantly
      attenuated the infarction. In conclusion our results suggest that p53 is
      implicated in ischaemia/reperfusion injury and that preconditioning
      counterbalances this effect via PI3K-Akt-Mdm2 phosphorylation.

PMID- 14644433
TI  - Insulin stimulates glucose metabolism via the pentose phosphate pathway in
      Drosophila Kc cells.
AB  - Drosophila melanogaster has become a prominent and convenient model for analysis
      of insulin action. However, to date very little is known regarding the effect of
      insulin on glucose uptake and metabolism in Drosophila. Here we show that, in
      contrast to effects seen in mammals, insulin did not alter [(3)H]2-deoxyglucose
      uptake and in fact decreased glycogen synthesis ( approximately 30%) in embryonic
      Drosophila Kc cells. Insulin significantly increased ( approximately 1.5-fold)
      the production of (14)CO(2) from D-[1-(14)C]glucose while the production of
      (14)CO(2) from D-[6-(14)C]glucose was not altered. Thus, insulin-stimulated
      glucose oxidation did not occur via increasing Krebs cycle activity but rather by
      stimulating the pentose phosphate pathway. Indeed, inhibition of the oxidative
      pentose phosphate pathway by 6-aminonicotinamide abolished the effect of insulin
      on (14)CO(2) from D-[U-(14)C]glucose. A corresponding increase in lactate
      production but no change in incorporation of D-[U-(14)C]glucose into total lipids
      was observed in response to insulin. Glucose metabolism via the pentose phosphate
      pathway may provide an important source of 5'-phosphate for DNA synthesis and
      cell replication. This novel observation correlates well with the fact that
      control of growth and development is the major role of insulin-like peptides in
      Drosophila. Thus, although intracellular signaling is well conserved, the
      metabolic effects of insulin are dramatically different between Drosophila and
      mammals.

PMID- 14644434
TI  - Production of unnatural glucosides of curcumin with drastically enhanced water
      solubility by cell suspension cultures of Catharanthus roseus.
AB  - Catharanthus roseus cell suspension cultures converted exogenously supplied
      curcumin to a series of glucosides, none of which has been found in nature so
      far. The efficiency of glucosylation was dependent on culture stage of the cells
      and medium sucrose concentration. Methyl jasmonate and salicylic acid enhanced
      the glucoside formation only when they were added to the cultures prior to the
      addition of curcumin. The glucoside yield was 2.5 micromol/g fresh weight of the
      cells at an optimal culture condition. The water solubility of curcumin-4',4"-O
      beta-D-digentiobioside was 0.65 mmol/ml, which was 20 million-fold higher than
      that of curcumin.

PMID- 14644435
TI  - Selection of novel structural zinc sites from a random peptide library.
AB  - Zinc ion (Zn(2+)) can be coordinated with four or three amino acid residues to
      stabilize a protein's structure or to form a catalytic active center. We used
      phage display selection of a dodecamer random peptide library with Zn(2+) to
      identify structural zinc sites. The binding specificity for Zn(2+) of selected
      sequences was confirmed using enzyme-linked immunosorbent and competitive
      inhibition assays. Circular dichroism spectra indicated that the interaction with
      Zn(2+) induced a change in conformation, which means the peptide acts as a
      structural zinc site. Furthermore, a search of protein databases revealed that
      two selected sequences corresponded to parts of natural zinc sites of copper/zinc
      superoxide dismutase and zinc-containing ferredoxin. We demonstrated that Zn(2+)
      binding sequences selected from the random combinatorial library would be
      candidates for artificial structural zinc sites.

PMID- 14644436
TI  - PIAS1 enhances SUMO-1 modification and the transactivation activity of the major
      immediate-early IE2 protein of human cytomegalovirus.
AB  - The protein inhibitor of activated STAT1 (PIAS1), known to be a small ubiquitin
      like modifier (SUMO) E3 ligase, was found to interact with the human
      cytomegalovirus IE2 protein. We found that the sumoylation of IE2 was markedly
      enhanced by wild-type PIAS1 but not by a mutant containing a Cys to Ser
      substitution at position 351 (C351S) within the RING finger-like domain. In
      target reporter gene assays, wild-type PIAS1, but not the C351S mutant, enhanced
      the IE2-mediated transactivations of viral polymerase promoter and cellular
      cyclin E promoter and this augmentation required the intact sumoylation sites of
      IE2. Our results suggest that PIAS1 acts as a SUMO E3 ligase toward IE2 and that
      it may regulate the transactivation function of IE2. To our knowledge, IE2 is the
      first viral target found to be regulated by a SUMO E3 ligase.

PMID- 14644437
TI  - Coordinate expression of the alpha and beta subunits of heterotrimeric G proteins
      involves regulation of protein degradation in CHO cells.
AB  - Individual cell types express a characteristic balance between heterotrimeric G
      protein alpha and betagamma subunits, but little is known about the regulatory
      mechanism. We systemically examined the regulatory mechanism in CHO cells. We
      found that expression of Galphas, Galphai2, and Galphaq proteins increased in
      direct proportion to the increase of Gbeta1gamma2 overexpressed transiently.
      Expression of Gbeta protein also increased following overexpression of Galphas,
      Galphai2, and Galphaq. The Gbetagamma overexpression stimulated degradation of
      Gbeta in contrast to reduction of Galphas degradation. We conclude that
      coordinate expression of the G protein subunits involves regulation of protein
      degradation via proteasome in CHO cells.

PMID- 14644438
TI  - Cyclophilin sensitivity to sanglifehrin A can be correlated to the same specific
      tryptophan residue as cyclosporin A.
AB  - Sanglifehrin A (SFA) is a recently discovered immunosuppressant drug that shares
      its intracellular target with the major immunosuppressant drug cyclosporin A
      (CsA). Both bind to and inhibit the cyclophilins, a diverse family of proteins
      found throughout nature that share a conserved catalytic domain. Although they
      share this common protein target, the mechanism of action of the cyclophilin-SFA
      complex has been reported as distinct from that of the well-studied cyclophilin
      CsA complex. The X-ray structure of a macrolide analogue of SFA's cyclic region
      complexed with cyclophilin A has recently been resolved, but this left the
      placement of the linear region of SFA unresolved. Using five cyclophilins from
      the fission yeast Schizosaccharomyces pombe, and a mutant of one of these
      proteins, SpCyp3-F128W, we have shown that the sensitivity of cyclophilins to SFA
      can be correlated to the same specific tryptophan residue that has previously
      been identified to correlate to CsA sensitivity, and that the tail of SFA may be
      responsible for mediating this sensitivity.

PMID- 14644439
TI  - A PERIOD inhibitor buffer introduces a delay mechanism for CLK/CYC-activated
      transcription.
AB  - We investigated the functions of clock genes period (per) and timeless (tim) in
      establishing negative feedback on circadian transcription factors clock/cycle
      (Clk/cyc) in Drosophila. We show that PER protein persists for several hours
      after rapid degradation of TIM in the morning. We observed in cell culture that
      isolated PER inhibits CLK/CYC-activated transcription in the absence of TIM and
      we further demonstrated for the first time in vivo that PER accumulation in a tim
      loss-of-function mutant background causes efficient inhibition of CLK/CYC
      dependent transcription. These results identify PER to be the main inhibitor for
      CLK/CYC and they suggest a delay mechanism during early morning, when PER
      protein, after degradation of TIM, forms an inhibitor buffer for CLK/CYC that
      attenuates the restart of the next cycle of CLK/CYC-activated transcription.
      While TIM likely enhances the inhibition of CLK/CYC by PER in the dark, our
      results suggest a reduction of PER-mediated inhibition by TIM in light.

PMID- 14644440
TI  - Essential role of the low density lipoprotein receptor-related protein in
      vascular smooth muscle cell migration.
AB  - The low density lipoprotein receptor-related protein (LRP) is a multifunctional
      cell surface receptor highly expressed in human aortic smooth muscle cells. In
      the present study, we used the short interfering RNA (siRNA) technique to explore
      the role of LRP in smooth muscle cell migration. We identified an LRP-specific
      siRNA that selective silences LRP expression in human aortic smooth muscle cells.
      As a consequence, LRP-mediated ligand degradation was significantly reduced. More
      important, we found that platelet-derived growth factor-dependent cell migration
      was inhibited in cells transfected with LRP siRNA. These results demonstrate an
      important role of LRP in smooth muscle cell migration.

PMID- 14644441
TI  - Intracellular trafficking of CLN3, the protein underlying the childhood
      neurodegenerative disease, Batten disease.
AB  - Juvenile neuronal ceroid lipofuscinoses (Batten disease) is a progressive
      neurodegenerative disorder resulting from mutations in the CLN3 gene, which
      encodes a hydrophobic 438 amino acid protein of unknown function. Prior studies
      have shown that CLN3 is expressed in multiple tissues, with highest levels in
      brain and testis. Experiments using cells overexpressing CLN3 indicate that CLN3
      is a lysosomal resident protein. However, studies to date have not addressed
      trafficking of endogenous CLN3. As such, the purpose of the present study was two
      fold. First, to develop a culture model to allow evaluation of native CLN3
      transport. Second, to utilize available epitope-specific antibodies to determine
      if CLN3 reaches the plasma membrane en route to the lysosome. Our data using a
      NCCIT (embryonic testicular carcinoma) cell model coupled with surface
      biotinylation and antibody trapping demonstrated that at least a proportion of
      CLN3 trafficks to the lysosome via the cell membrane. Moreover, inhibition of the
      micro3A subunit of the AP-3 adapter protein complex increased levels of CLN3 at
      the cell surface.

PMID- 14644442
TI  - Molecular classification of cancer types from microarray data using the
      combination of genetic algorithms and support vector machines.
AB  - Simultaneous multiclass classification of tumor types is essential for future
      clinical implementations of microarray-based cancer diagnosis. In this study, we
      have combined genetic algorithms (GAs) and all paired support vector machines
      (SVMs) for multiclass cancer identification. The predictive features have been
      selected through iterative SVMs/GAs, and recursive feature elimination post
      processing steps, leading to a very compact cancer-related predictive gene set.
      Leave-one-out cross-validations yielded accuracies of 87.93% for the eight-class
      and 85.19% for the fourteen-class cancer classifications, outperforming the
      results derived from previously published methods.

PMID- 14644443
TI  - Plant mitochondrial nucleoside diphosphate kinase is attached to the membrane
      through interaction with the adenine nucleotide translocator.
AB  - This study shows that the plant mitochondrial nucleoside diphosphate kinase
      (mNDPK) localizes to both the intermembrane space and to the mitochondrial inner
      membrane. We show that mNDPK is very firmly attached to the membrane. Co
      immunoprecipitation experiments identified the adenine nucleotide translocator as
      an interaction partner. This is the first report showing a direct association
      between these two proteins, although previous studies have shown metabolic
      cooperation between them. Possible consequences for mitochondrial energy
      metabolism are discussed.

PMID- 14644444
TI  - Polyhalogenated benzo- and naphthoquinones are potent inhibitors of plant and
      bacterial ureases.
AB  - Polyhalogenated benzo- and naphthoquinones were found to be potent inhibitors of
      pure ureases from Bacillus pasteurii and Canavalia ensiformis. They also
      inhibited ureases in whole cells of Helicobacter pylori, Klebsiella oxytoca and
      Proteus mirabilis. Inhibition was non-competitive with K(i) values in the
      micromolar range or below. Inhibition was irreversible as shown by equilibrium
      dialysis. Inhibitory power decreased considerably when halogens were replaced by 
      OH, -CN, alkoxy or alkyl groups.

PMID- 14644445
TI  - A left-handed 3(1) helical conformation in the Alzheimer Abeta(12-28) peptide.
AB  - We show for the first time that the secondary structure of the Alzheimer beta
      peptide is in a temperature-dependent equilibrium between an extended left-handed
      3(1) helix and a flexible random coil conformation. Circular dichroism spectra,
      recorded at 0.03 mM peptide concentration, show that the equilibrium is shifted
      towards increasing left-handed 3(1) helix structure towards lower temperatures.
      High resolution nuclear magnetic resonance (NMR) spectroscopy has been used to
      study the Alzheimer peptide fragment Abeta(12-28) in aqueous solution at 0
      degrees C and higher temperatures. NMR translation diffusion measurements show
      that the observed peptide is in monomeric form. The chemical shift dispersion of
      the amide protons increases towards lower temperatures, in agreement with the
      increased population of a well-ordered secondary structure. The solvent exchange
      rates of the amide protons at 0 degrees C and pH 4.5 vary within at least two
      orders of magnitude. The lowest exchange rates (0.03-0.04 min(-1)) imply that the
      corresponding amide protons may be involved in hydrogen bonding with neighboring
      side chains.

PMID- 14644447
TI  - Caspase 8 mediated apoptotic cell death induced by beta-sheet forming polyalanine
      peptides.
AB  - Expansion of a polyalanine stretch from 10 to 12-17 residues in the N-terminus of
      the protein PABP2 has been implicated in the genetically acquired disease
      oculopharyngeal muscular dystrophy, characterized by nuclear protein deposits.
      Here we report a correlation between the structural properties and cell toxicity
      of two peptides mimicking the N-terminal domain of PABP2: one containing seven
      and the other 11 uninterrupted alanine residues. Consistent with earlier
      observations, the longer peptide (11-ala) was found to adopt beta-sheet structure
      while the shorter one (7-ala) formed alpha-helix over a wide range of
      concentrations ( approximately 20-500 microM). We observed that treatment with 11
      ala resulted in significantly enhanced death of Chinese hamster V79 cells,
      compared to the effect of treatment with 7-ala, via the cytochrome c mediated
      apoptotic pathway. Increases in caspase 8 and caspase 3 activity were also
      observed in human cells (K562) treated with 11-ala. These results indicate that
      the toxicity of pathogenic peptides is directly linked to their beta-sheet
      structure and also support recent observations that small oligomeric species of
      peptides and proteins are the key toxic elements in causing protein aggregation
      diseases.

PMID- 14644446
TI  - Antagonism of botulinum toxin type A-induced cleavage of SNAP-25 in rat cerebral
      synaptosome by toosendanin.
AB  - Toosendanin (TSN), a triterpenoid derivative extracted from Chinese traditional
      medicine, has been demonstrated to be an effective cure for experimental
      botulism. This study is designed to explore its antibotulismic mechanism by
      Western blotting. The results showed that TSN incubation did not change the
      electrophoresis pattern and the amounts of synaptosomal-associated protein of 25
      kDa (SNAP-25), syntaxin and synaptobrevin/vesicle-associated membrane protein in
      rat cerebral synaptosomes, but made the synaptosomes completely resistant to
      botulinum neurotoxin A (BoNT/A)-mediated cleavage of SNAP-25. After binding of
      BoNT/A to synaptosomes, TSN still partially antagonized the toxin-mediated
      cleavage of SNAP-25. However, TSN-incubated synaptosomal membrane fraction did
      not resist the cleavage of SNAP-25 by the light chain of BoNT/A. It is suggested
      that the antibotulismic effect of TSN results from blocking the toxin's approach
      to its enzymatic substrate.

PMID- 14644448
TI  - Statins induce suppressor of cytokine signaling-3 in macrophages.
AB  - Our previous study has shown that lipophilic 3-hydroxy-3-methyl-glutaryl coenzyme
      A reductase inhibitors of statins can inhibit interferon-gamma-induced inducible
      nitric oxide synthase gene expression in RAW264.7 macrophages. In this study, we
      showed that lovastatin and fluvastatin are able to upregulate the mRNA expression
      of the suppressor of cytokine signaling-3 (SOCS-3) gene. This effect is specific
      for SOCS-3 and could be blocked by mevalonate, farnesyl pyrophosphate and
      geranylgeranyl pyrophosphate, while it was not affected by inhibitors of protein
      kinase C and A, mitogen-activated protein/extracellular signal-regulated kinase
      kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, Src, Raf
      and Rho kinase. SOCS-3 expression results in the inhibition of interferon-gamma-,
      interleukin-6- and macrophage colony-stimulating factor-elicited signal
      transducer and activator of transcription phosphorylation, suggesting a novel
      anti-inflammatory mechanism of statins to down-modulate the functions of
      interferon-gamma-activated macrophages.

PMID- 14644449
TI  - Hsp105 but not Hsp70 family proteins suppress the aggregation of heat-denatured
      protein in the presence of ADP.
AB  - Hsp105alpha and Hsp105beta are mammalian members of the Hsp105/110 family, a
      diverged subgroup of the Hsp70 family. Here, we show that Hsp105alpha and
      Hsp105beta bind non-native protein through the beta-sheet domain and suppress the
      aggregation of heat-denatured protein in the presence of ADP rather than ATP. In
      contrast, Hsc70/Hsp40 suppressed the aggregation of heat-denatured protein in the
      presence of ATP rather than ADP. Furthermore, the overexpression of Hsp105alpha
      but not Hsp70 in COS-7 cells rescued the inactivation of luciferase caused by ATP
      depletion. Thus, Hsp105/110 family proteins are suggested to function as a
      substitute for Hsp70 family proteins to suppress the aggregation of denatured
      proteins in cells under severe stress, in which the cellular ATP level decreases
      markedly.

PMID- 14644450
TI  - Inhibition of ubiquitin/proteasome-dependent proteolysis in Saccharomyces
      cerevisiae by a Gly-Ala repeat.
AB  - The glycine-alanine (GA) repeat of the Epstein-Barr virus nuclear antigen-1
      inhibits in cis ubiquitin-dependent proteolysis in mammalian cells through a yet
      unknown mechanism. In the present study we demonstrate that the GA repeat targets
      an evolutionarily conserved step in proteolysis since it can prevent the
      degradation of proteasomal substrates in the yeast Saccharomyces cerevisiae.
      Insertion of yeast codon-optimised recombinant GA (rGA) repeats of different
      length in green fluorescent protein reporters harbouring N-end rule or ubiquitin
      fusion degradation signals resulted in efficient stabilisation of these
      substrates. Protection was also achieved in rpn10delta yeast suggesting that this
      polyubiquitin binding protein is not required for the rGA effect. The conserved
      effect of the GA repeat in yeast opens the possibility for the use of genetic
      screens to unravel its mode of action.

PMID- 14644451
TI  - Prediction of the binding site on E1 in the assembly of the pyruvate
      dehydrogenase multienzyme complex of Bacillus stearothermophilus.
AB  - The beta-subunit (E1beta) of the pyruvate decarboxylase (E1, alpha(2)beta(2))
      component of the Bacillus stearothermophilus pyruvate dehydrogenase complex was
      comparatively modelled based on the crystal structures of the homologous 2
      oxoisovalerate decarboxylase of Pseudomonas putida and Homo sapiens. Based on
      this homology modelling, alanine-scanning mutagenesis studies revealed that the
      negatively charged side chain of Glu285 and the hydrophobic side chain of Phe324
      are of particular importance in the interaction with the peripheral subunit
      binding domain of the dihydrolipoyl acetyltransferase component of the complex.
      These results help to identify the site of interaction on the E1beta subunit and
      are consistent with thermodynamic evidence of a mixture of electrostatic and
      hydrophobic interactions being involved.

PMID- 14644452
TI  - Presence of the inositol 1,4,5-triphosphate receptor isoforms in the nucleoplasm.
AB  - Although the inositol 1,4,5-triphosphate (IP(3))-induced nuclear Ca(2+) release
      has been shown to play key roles in nuclear functions, the presence of IP(3)
      receptor (IP(3)R)/Ca(2+) channels in the nucleoplasm has not been found.
      Recently, the IP(3)R/Ca(2+) channels were reported to exist in the nucleoplasmic
      reticulum structure, an extension of the nuclear envelope. Here we investigated
      the potential existence of the IP(3)Rs in the nucleoplasm and found the presence
      of all three IP(3)R isoforms in neuroendocrine and non-neuroendocrine cells. The
      IP(3)Rs were widely scattered in the nucleoplasm, localizing in both the
      heterochromatin and euchromatin regions.

PMID- 14644453
TI  - Amadori-glycated phosphatidylethanolamine induces angiogenic differentiations in
      cultured human umbilical vein endothelial cells.
AB  - Glycation has been implicated in the endothelial dysfunction that contributes to
      both diabetes- and aging-associated vascular complications. The aim of the
      present study was to determine whether Amadori-glycated phosphatidylethanolamine
      (Amadori-PE), a lipid-linked glycation compound that is formed at an increased
      rate in hyperglycemic states, affected proliferation, migration and tube
      formation of cultured human umbilical vein endothelial cells (HUVEC). Amadori-PE
      at a low concentration of less than 5 microM significantly enhanced these three
      factors involved in angiogenesis. Furthermore, stimulation of HUVEC with Amadori
      PE resulted in secretion of matrix metalloproteinase 2 (MMP-2), a pivotal enzyme
      in the initial step of angiogenesis. Our results demonstrated for the first time
      that Amadori-PE may be an important compound that promotes vascular disease as a
      result of its angiogenic activity on endothelial cells. We also demonstrated that
      MMP-2 is a primary mediator of Amadori-PE-driven angiogenesis.

PMID- 14644454
TI  - Bumetanide-induced enlargement of the intercellular space in the stria vascularis
      critically depends on Na+ transport.
AB  - The intercellular space in the stria vascularis (intrastrial space) is a closed
      space and isolated from both the endolymph and the perilymph in normal tissue.
      Loop diuretics such as bumetanide and furosemide cause an acute enlargement of
      the intrastrial space in association with a decline in the endocochlear
      potential. It is known that bumetanide inhibits the Na+-K+-2Cl- cotransporter,
      which is expressed abundantly in the basolateral membrane of marginal cells. We
      studied ionic mechanisms underlying the bumetanide-induced enlargement of the
      intrastrial space using perilymphatic perfusion in guinea pigs. Perilymphatic
      perfusion with artificial perilymph containing 100 microM bumetanide caused
      marked enlargement of the intrastrial space, as reported previously. Removal of
      K+ from the perilymph did not affect the bumetanide-induced enlargement, whereas
      removal of Na+ from the perilymph inhibited it almost completely. Perilymph
      containing 1 mM amiloride also inhibited the enlargement of the intrastrial space
      almost completely. These results indicate that perilymphatic Na+, but not K+, and
      amiloride-sensitive pathways are essential to the bumetanide-induced enlargement
      of the intrastrial space. Two possible pathways could yield these results. Na+ in
      the perilymph could enter the endolymph via Reissner's membrane or the basilar
      membrane; Na+ in the endolymph would then be taken up by marginal cells via the
      apical membrane and secreted into the intrastrial space by Na+-K+-ATPase in the
      basolateral membrane of them. Another, less likely possibility is that Na+ in the
      perilymph is transported into basal cells or fibrocytes in the spiral ligament,
      then into intermediate cells via gap junctions, and finally secreted into the
      intrastrial space via Na+-K+-ATPase of intermediate cells.

PMID- 14644455
TI  - Aminoguanidine reduces cisplatin ototoxicity.
AB  - Cisplatin is known to cause high-frequency neurosensory hearing loss. While
      reactive oxygen species have been shown to play a role, reactive nitrogen species
      have been implicated, but not proven to be involved, in cisplatin ototoxicity.
      The purpose of the present study was to investigate the role of nitric oxide
      (*NO) in cisplatin ototoxicity by administering aminoguanidine (AG), a relatively
      specific inhibitor of inducible nitric oxide synthase (iNOS), in conjunction with
      cisplatin. Rats were injected with cisplatin, AG, or both. Auditory brainstem
      evoked responses (ABR) were measured before and 3 days after cisplatin
      administration. The cochlear tissue was then assayed for *NO and malondialdehyde.
      Cisplatin alone caused significant ABR threshold shifts at all stimuli tested,
      whereas AG alone caused no shifts. There was a significant reduction in threshold
      shift for clicks and 16 kHz tone bursts (but not 32 kHz) when AG was given with
      cisplatin. The malondialdehyde concentration (but not the *NO concentration) in
      the AG/cisplatin group was significantly lower than that of the cisplatin group.
      This suggests that AG reduces cisplatin ototoxicity by directly scavenging
      hydroxyl radicals. The iNOS pathway may play a role in the generation of free
      radicals and hearing loss resulting from cisplatin administration, but this
      conclusion was not supported by our data.

PMID- 14644456
TI  - Impaired gap encoding in aged mouse inferior colliculus at moderate but not high
      stimulus levels.
AB  - Age-related deterioration of auditory temporal acuity has been identified as a
      contributing factor in presbycusis. In the present study, the effects of aging
      and stimulus level on gap encoding and gap recovery functions were investigated
      by measuring near-field auditory evoked potentials in the inferior colliculus of
      eight 3 month old and eight 24 month old CBA/CaJ mice, in response to gap stimuli
      embedded in broadband noise (40, 60, and 80 dB SPL). Gap encoding was assessed by
      measuring latencies and amplitudes of peak features of the near-field response,
      and also with a procedure that calculated the root mean square of the response
      within specific time windows. The chief differences in gap encoding between young
      and old mice were longer gap thresholds, slower recovery functions, and longer
      response peak latencies for old mice at 60, but not 80 dB SPL, although the
      latency of the earliest measured peak remained delayed for this condition in the
      old compared with the young mice. These results demonstrate that age-related
      changes in temporal acuity may interact with stimulus level, and suggest that
      adequate amplification may be critically important for maintaining temporal
      acuity with advancing age.

PMID- 14644457
TI  - New variations on the derivation of spectro-temporal receptive fields for primary
      auditory afferent axons.
AB  - The spectro-temporal receptive field [Hear. Res 5 (1981) 147; IEEE Trans BME 15
      (1993) 177] provides an explicit image of the spectral and temporal aspects of
      the responsiveness of a primary auditory afferent axon. It exhibits the net
      effects of the competition between excitatory and inhibitory (or suppressive)
      phenomena. In this paper, we introduce a method for derivation of the spectro
      temporal receptive field directly from a second-order Wiener kernel (produced by
      second-order reverse correlation between spike responses and broad-band white
      noise stimulus); and we expand the concept of the spectro-temporal receptive
      field by applying the new method not only to the second-order kernel itself, but
      also to its excitatory and inhibitory subkernels. This produces separate spectro
      temporal images of the excitatory and inhibitory phenomena putatively underlying
      the competition. Applied, in simulations, to models with known underlying
      excitatory and suppressive tuning and timing properties, the method successfully
      extracted a faithful image of those properties for excitation and one for
      inhibition. Applied to three auditory axons from the frog, it produced images
      consistent with previously published physiology.

PMID- 14644458
TI  - Developmental differences in susceptibility to neomycin-induced hair cell death
      in the lateral line neuromasts of zebrafish (Danio rerio).
AB  - Mechanosensory hair cells of the inner ear are susceptible to death when exposed
      to a variety of drugs including aminoglycoside antibiotics. During avian and
      mammalian development, there is a period of relative insensitivity to
      aminoglycoside-induced hair cell death. This study was designed to test the
      hypothesis that zebrafish (Danio rerio) have developmental differences in
      sensitivity to aminoglycoside-induced hair cell death in the lateral line
      neuromasts. Larval zebrafish of various ages were exposed to several
      concentrations of neomycin, and their hair cells were examined using the
      potentiometric vital dye, DASPEI. Results indicate that zebrafish larvae aged 4
      days post-fertilization are relatively insensitive to aminoglycoside-induced hair
      cell death compared to older fish. Thus zebrafish hair cells show developmental
      differences in sensitivity to aminoglycoside-induced death similar to those
      reported for inner ear hair cells of birds and mammals.

PMID- 14644459
TI  - Frequency specificity of 40-Hz auditory steady-state responses.
AB  - Auditory steady-state responses (ASSR) to amplitude modulated (AM) tones with
      carrier frequencies between 250 and 4000 Hz and modulation frequencies near 40 Hz
      were recorded using a 37-channel neuro-magnetometer placed above the auditory
      cortex contralateral to the stimulated right ear. The ASSR sources were likely in
      the primary auditory cortex, located more anteriorly and more medially than the
      N1m sources. The ASSR amplitude decreased with increasing carrier frequency, the
      amplitude at 250 Hz being three times larger than at 4000 Hz. The amplitude of
      the ASSR to a test sound decreased in the presence of an interfering second AM
      sound. This suppression of the ASSR to the test stimulus was greater when the
      carrier frequency of the interfering stimulus was higher than that of the test
      tone and was greater when the test stimulus had a lower carrier frequency.
      Similar frequency specificity was observed when the interfering sound was a non
      modulated pure tone. These results differ from those found for the ASSR elicited
      by modulation frequencies above 80 Hz or for the transient brainstem and middle
      latency responses and suggest substantial interactions between phase-locked
      activities at the level of the primary auditory cortex.

PMID- 14644460
TI  - Contribution of stapedial artery to blood flow in the cochlea and its surrounding
      bone.
AB  - This study was performed to elucidate the contribution of the stapedial artery
      (SA)--which has been considered to be independent of the vertebrobasilar system-
      to blood flow in the ear by observing ear blood flow in Sprague-Dawley rats. A
      laser-Doppler (LD) probe was positioned on the bony wall of the cochlear basal
      turn after removal of the middle ear mucosa. The LD output was measured while
      either or both the SA and the anterior inferior cerebellar artery (AICA) were
      occluded. The LD output decreased to 70.6+/-2.5% (mean+/-S.D.) of the baseline
      value following SA occlusion, and to 58.0+/-7.8% following AICA occlusion in 12
      animals. The rebound phenomenon of blood flow, which is a type of autoregulation,
      was only observed after releasing AICA occlusion. Simultaneous occlusion of the
      SA and AICA decreased the LD output to 27.0+/-5.5% of the baseline value. The
      role of the contribution of the SA and AICA to the LD output is discussed.

PMID- 14644461
TI  - Cochlear function in young and adult Fischer 344 rats.
AB  - Fischer 344 (F344) rats are often used as an animal model for investigation of
      the mechanisms underlying age-related hearing loss. The aim of this study was to
      assess cochlear function in young (1-month-old) and adult (6-month-old) F344 rats
      using recording of otoacoustic emissions and auditory brainstem responses (ABRs).
      The results were compared with control groups of Long Evans (LE) rats of the same
      ages. The results demonstrate a significant increase in the hearing threshold in
      F344 rats in comparison with LE rats, expressed mainly at low frequencies (1-2
      kHz). In F344 rats, transient evoked otoacoustic emissions were not measurable
      and distortion product otoacoustic emissions could be detected within a frequency
      range of 2.4-6.3 kHz. Tympanometric measurements did not reveal any differences
      in middle ear parameters between F344 and LE rats. The amplitudes of click-evoked
      ABRs were significantly lower in 6-month-old F344 rats than in LE rats, but other
      parameters of the ABRs were almost identical in both rat strains. The results
      demonstrate a significant deficit in low-frequency hearing and altered
      otoacoustic emissions in both young and adult F344 rats, suggesting a defect of
      the inner ear sensory epithelium at the apical part of the cochlea.

PMID- 14644462
TI  - Microtubule-associated protein 2 (MAP2) expression during synaptic plasticity in
      the guinea pig cochlea.
AB  - The expression of different isoforms of microtubule-associated proteins 2 (MAP2),
      including the low molecular weight form MAP2c present mainly in developing
      neurons, was investigated in the primary auditory neurons after alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) perfusion in the guinea pig
      cochlea. MAP2 expression appeared to be tightly regulated in the repairing
      neurons. Neurite regrowth seems to involve the MAP2c isoform. In cochlear
      neurons, mechanisms involved in the period of development might be reactivated
      after excitotoxic injury in the mature cochlea.

PMID- 14644463
TI  - Noise improves suprathreshold discrimination in cochlear-implant listeners.
AB  - The present study aimed to examine the effect of noise on vowel-like
      suprathreshold discrimination in cochlear-implant listeners. The task was to
      detect an increment in level at the middle harmonic (400 Hz) in the background of
      a seven-harmonic complex from 100 to 700 Hz in 100-Hz steps. The task was
      performed in the absence (control) and presence of a white noise presented over a
      20-35-dB range from inaudible to loud. The present result shows that
      discrimination of suprathreshold harmonic stimuli was significantly enhanced,
      particularly at the soft signal level, with suprathreshold noise. This result
      suggests that tuning of the noise level is required to optimize performance of
      different tasks in cochlear implants.

PMID- 14644464
TI  - Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation.
AB  - Rat cisternal (CSF) hypocretin-1 in cerebrospinal fluid was measured after 6 or
      96 h of REM sleep deprivation and following 24 h of REM sleep rebound. REM
      deprivation was found to increase CSF hypocretin-1 collected at zeitgeber time
      (ZT) 8 but not ZT0. Decreased CSF hypocretin levels were also observed at ZT8
      after 24 h of REM sleep rebound. These results suggest that REM sleep deprivation
      activates and REM sleep rebound inhibits the hypocretin system. Increased
      hypocretin tone during REM deprivation may be important in mediating some of the
      effects of REM sleep deprivation such as antidepressant effects, hyperphagia and
      increased sympathetic activity.

PMID- 14644465
TI  - Beta- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide
      production in mice brain.
AB  - The pro-opiomelanocortin-derived peptide alpha-melanocyte stimulating hormone
      (alpha-MSH) mediates many diverse physiological actions, including anti
      inflammatory and immunomodulatory effects. However, little is known about the
      physiological roles of the other melanocortins, beta- and gamma-MSH. Here, we
      investigated the effects of melanocortin peptides in an in vivo neuroinflammation
      model. Six hours following intracisternal (i.c.) administration of 10 microg
      lipopolysaccharide (LPS) to mice a five-fold increase in the nitric oxide (NO)
      level was seen in the animals' brains, when detected by electron paramagnetic
      resonance (EPR). All tested melanocortins, alpha-, beta-, gamma1- and gamma2-MSH
      (0.001-10 nmol/mouse i.c.), dose dependently reduced the LPS induced increases in
      brain NO, with an order of effectiveness: beta-MSH > or = gamma1-MSH=gamma2
      MSH>alpha-MSH. Our results suggest specialized functions of beta- and gamma-MSH
      melanocortins in inflammatory signal modulation in the brain.

PMID- 14644466
TI  - Short-term, D2 receptor blockade induces synaptic degeneration, reduces levels of
      tyrosine hydroxylase and brain-derived neurotrophic factor, and enhances D2
      mediated firing in the ventral pallidum.
AB  - Repeated treatments with neuroleptics are associated with biochemical and
      morphological alterations in forebrain neurons as well as an upregulation of D2
      mediated changes in neuronal function. The present study evaluated the
      histological and physiological effects of three once-daily treatments with two
      chemically divergent neuroleptics, haloperidol (1 mg/kg i.p./day) and eticlopride
      (3 mg/kg i.p./day), measured in rats 24 h after the last injection. It was
      determined that this short-term antagonism of D2-like receptors induced fiber and
      terminal degeneration and significantly decreased tyrosine hydroxylase (TH) and
      brain-derived neurotrophic factor (BDNF) immunoreactivity in the ventral pallidum
      (VP), as determined by optical density measurements. While other forebrain
      regions demonstrated changes in TH and BDNF, the neurodegeneration profile was
      unique to the VP. This was accompanied by an enhancement in the efficacy of the
      D2 agonist quinpirole to increase spiking rate of VP neurons recorded in chloral
      hydrate-anesthetized rats. These data indicate that short-term treatments with D2
      antagonists are sufficient to induce changes in the biochemical and morphological
      profiles uniquely within the VP. Moreover, the functional ramifications of these
      changes appear to include profound alterations in the way dopamine regulates
      neuronal activity in this region.

PMID- 14644467
TI  - Role of corticotropin-releasing factor and its receptor in nociceptive modulation
      in the central nucleus of amygdala in rats.
AB  - Corticotropin-releasing factor (CRF) plays important physiological functions in
      the central nervous system. The present study was performed to investigate the
      role of CRF and CRF receptor in nociceptive modulation in the central nucleus of
      amygdala (CeA) of rats. The hindpaw withdrawal latency (HWL) to noxious thermal
      and mechanical stimulation increased significantly after intra-CeA administration
      of 0.1 and 0.01 nmol of CRF, but not 0.001 nmol, indicating that CRF induces
      antinociceptive effects in the CeA of rats. The antinociceptive effect may be due
      to the dose of CRF was attenuated by intra-CeA administration of 0.1 nmol alpha
      hCRF9-41, a selective CRF receptor antagonist, suggesting that the CRF-induced
      antinociception is mediated by the CRF receptors in the CeA. Furthermore, the HWL
      to both thermal and mechanical stimulation decreased significantly after intra
      CeA administration of alpha-hCRF9-41 alone, suggesting an involvement of
      endogenous CRF in the CeA in nociceptive modulation. The present study
      demonstrated that both exogenous and endogenous CRF plays an antinociceptive
      effect in the CeA, the effect is mediated by CRF receptor.

PMID- 14644468
TI  - Protective effects of brief intra- and delayed postischemic hypothermia in a
      transient focal ischemia model in the neonatal rat.
AB  - Hypothermia provides neuroprotection in virtually all animal models of ischemia,
      including adult stroke models and the neonatal hypoxic-ischemic (HI) model. In
      these studies, brief periods of hypothermia are examined in a neonatal model
      employing transient focal ischemia in a 7-day-old rat pup. Pups underwent
      permanent middle cerebral artery (MCA) occlusion coupled with a temporary (1 h)
      occlusion of the ipsilateral common carotid artery (CCA). This study included
      five treatment groups: (1) normothermic (Normo)-brain temperature was maintained
      at 37 degrees C; (2) intraischemic hypothermia (IntraH)-28 degrees C during the 1
      h ischemic period only; (3) postischemic hypothermia (PostH)-28 degrees C for the
      second hour of reperfusion only; (4) late-onset postischemic hypothermia (LPostH)
      cooled to 28 degrees C for the fifth and sixth hours of reperfusion only; and (5)
      Shams. After various times (3 days-6 weeks), the lesion was assessed using 2,3,5
      triphenyltetrazolium chloride (TTC) or hematoxylin and eosin (H&E) stains.
      Intraischemic hypothermia resulted in significant protection in terms of
      survival, lesion size, and histology. Postischemic hypothermia was not effective
      in reducing lesion size early after ischemia, but significantly reduced the
      eventual long-term damage (2-6 weeks). Late-onset postischemic hypothermia did
      not reduce infarct volume. Therefore, both intraischemic and postischemic
      hypothermia provided neuroprotection in the neonatal rat, but with different
      effects on the degenerative time course. While there were no observable
      differences in simple behaviors or growth, all hypothermic conditions
      significantly reduced mortality rates. While the protection resulting from
      intraischemic hypothermia is similar to what is observed in other models, the
      degree of long-term ischemic protection observed after 1 h of postischemic
      hypothermia was remarkable and distinct from what has been observed in other
      adult or neonatal models.

PMID- 14644469
TI  - The human immunodeficiency virus type-1 transcription factor Tat produces
      elevations in intracellular Ca2+ that require function of an N-methyl-D-aspartate
      receptor polyamine-sensitive site.
AB  - Human immunodeficiency virus type-1 (HIV-1) infection is commonly associated with
      neuronal loss, as well as, cognitive and motor deficits collectively termed HIV-1
      associated dementia (HAD). Function of the HIV-1 transcription factor Tat,
      activation of N-methyl-D-aspartate (NMDA)-type glutamate receptors, and
      subsequent rapid rises in free intracellular Ca2+ have been implicated in the
      development of this neurological disorder. However, the role of specific NMDA
      receptor modulatory sites in mediating effects of Tat has not been examined. The
      present studies examined the ability of two variants of Tat protein (1-100 nM),
      Tat 1-72 and Tat 1-86, to produce rapid rises in intracellular Ca2+ in
      organotypic slice cultures of rat hippocampus. Further, these studies evaluated
      the role of an NMDA receptor polyamine-sensitive site in mediating Tat-induced
      elevations in intracellular Ca2+. Brief exposure (10 min) to each variant of Tat
      protein (>1 nM) markedly increased levels of intracellular Ca2+ in each region of
      the hippocampus to as much as 145% of controls. In contrast, exposure of cultures
      to a deletion mutant of Tat protein devoid of amino acids 31-61 (Tat Delta31-61)
      did not produce changes in intracellular Ca2+ levels. Most significantly,
      exposure to the NMDA receptor antagonist dizocilpine (MK801 20 microM) and the
      polyamine site antagonist arcaine (10 microM) significantly attenuated increases
      in intracellular Ca2+ levels when co-administered with either the Tat 1-72 or Tat
      1-86 amino acid variant of Tat. Thus, exposure of the hippocampus to Tat produces
      increases in intracellular Ca2+ levels that require function of an NMDA receptor
      polyamine-sensitive site and this may well contribute to the neurotoxic effects
      of HIV-1 infection. Polyamine-sensitive portions of this receptor may then
      represent novel therapeutic targets in the pharmacologic treatment of HAD-related
      neurotoxicity.

PMID- 14644470
TI  - The transition from controlled to compulsive drug use is associated with a loss
      of sensitization.
AB  - Rats provided limited daily access to cocaine (1 h) maintain stable levels of
      drug self-administration over time while those switched to longer access (6 h or
      more) exhibit escalating patterns of drug intake. These results are reminiscent
      of human recreational and compulsive drug-taking behavior, respectively. We found
      that the brains of cocaine-self-administering rats were also qualitatively
      different in subjects having experienced 6-h (Coc6h) daily access compared to 1-h
      (Coc1h) access. Fourteen days after an eight-day protocol of cocaine self
      administration, all subjects received one infusion of cocaine. Coc1h animals
      showed enhanced c-Fos reactivity in dopaminergic mesocorticolimbic brain regions
      and a sensitized locomotor response to IV cocaine. In contrast, both the neural
      and behavioral sensitization to cocaine was diminished in Coc6h animals. These
      data suggest that the transition to escalating patterns of drug use is associated
      with neuroadaptive changes that counteract those initially associated with
      controlled stable patterns of drug use.

PMID- 14644471
TI  - Subregion-specific differences in hippocampal activity between Delay and Trace
      fear conditioning: an immunohistochemical analysis.
AB  - Lesions of the hippocampus attenuate acquisition of the tone-shock contingency in
      Trace, but not in Delay fear conditioning. These findings suggest that
      hippocampal regions are differentially involved in these two forms of fear
      conditioning. The present study was aimed at testing the hypothesis that
      hippocampal neurons are differentially activated during acquisition and retrieval
      of Delay versus Trace fear conditioning. Male C57BL/6J mice were exposed to eight
      tone-shock pairings (in Trace conditioning the shock came 30 s after the tone),
      and tested for immobility upon reexposure to contextual stimuli or to one tone
      presentation. Ten brain regions were analyzed by immunohistochemistry for
      inducible transcription factors (ITF) c-Fos and Zif268 1.5 h after training,
      context test or tone test. Acquisition of both Delay and Trace fear conditioning
      produced significant induction of c-Fos in the majority of brain regions analyzed
      compared to naive control animals. Importantly, Delay fear conditioning caused a
      higher increase of c-Fos expression in the CA3 region of the hippocampus compared
      to Trace-trained animals. After cue reexposure, Zif268 levels in the dentate
      gyrus of the hippocampus were higher in Trace-conditioned than in Delay
      conditioned animals. In addition, reexposure-related c-Fos expression in the
      anterior cingulate cortex was significantly higher in Delay-conditioned animals
      than in Trace-conditioned animals. The present study confirms differential
      activation of hippocampal subregions in Delay and Trace fear conditioning.

PMID- 14644472
TI  - Successive depth variations in microvascular distribution of rat somatosensory
      cortex.
AB  - Although hemodynamic-based functional brain imaging techniques are powerful tools
      to explore the brain functions noninvasively, hemodynamic-based signal is
      strongly affected by spatial configuration of microvessels. Understanding the
      quantitative relations between microvascular structure and functional activity is
      therefore significant to make a valid signal interpretation for the imaging
      techniques. In the present study, we evaluated depth profiles of microvascular
      distributions in rat somatosensory subfields (barrel field, forelimb region,
      trunk region and hindlimb region) and characterized depth variations in
      microvascular structures, such as locations, lengths and directions of
      microvessels, throughout the cortical layers (I-VI). To obtain the accurate
      microvascular structure, we made a customized casting method by using confocal
      laser scanning microscope. We observed that microvascular distribution
      successively varied throughout the cortical layers (I-VI) and that the maximum
      number density of microvessels was consistently found in middle layers (III-V).
      In addition, superficial layers had relatively long microvessels, almost
      perpendicular to the cortical surface, whereas middle layers had short
      microvessels propagating in all directions. These regional differences in
      microvascular structures were closely related to the somatosensory subfields,
      e.g., barrel field was the greatest number density of microvessels among the
      investigated subfields. Based on these observations, we compared microvascular
      profiles with previously reported distribution patterns of tissue partial
      pressure of oxygen (pO2). The results showed that tissue pO2 was correlated with
      microvascular distribution in some but not all of the subfields. This finding
      shows that detailed microvascular profiles are helpful to investigate causal
      relationships between microvascular structure and functional activities in
      cerebral cortex.

PMID- 14644473
TI  - NAD(P)H oxidase, superoxide dismutase, catalase, glutathione peroxidase and
      nitric oxide synthase expression in subacute spinal cord injury.
AB  - Primary trauma to the spinal cord triggers a cascade of cellular and molecular
      events that promote continued tissue damage and expansion of the lesion for
      extended periods following the initial injury. Oxidative and nitrosative stresses
      play an important role in progression of spinal cord injury (SCI). In an attempt
      to explore the biochemical origin of oxidative/nitrosative stress associated with
      secondary SCI, we studied expression of the superoxide (O2*-)-generating enzyme,
      NAD(P)H oxidase, antioxidant enzymes [superoxide dismutase (CuZn SOD, Mn SOD),
      catalase, glutathione peroxidase (GPX)], nitric oxide synthases (NOS) and a
      byproduct of NO-O2*- interaction (nitrotyrosine) in the spinal cord tissues of
      rats 16 h and 14 days after surgical resections of a 5-mm segment of the cord
      below T8 or sham-operation. Immunodetectable NAD(P)H oxidase subunits (gp91phox
      and P67phox), Mn SOD, inducible NOS (iNOS), endothelial NOS (eNOS), and
      nitrotyrosine were elevated in the transected cords on day 1 and day 14. Neuronal
      NOS (nNOS) was unchanged on day 1 and significantly depressed on day 14. GPX was
      unchanged on day 1 and significantly elevated on day 14. Catalase was unchanged
      in the cord tissue surrounding the transection site at both points. Thus,
      concurrent upregulations of NAD(P)H oxidase, eNOS and iNOS (but not nNOS), work
      in concert to maintain oxidative and nitrosative stress in the injured cord
      tissue.

PMID- 14644474
TI  - A survival motor neuron:tetanus toxin fragment C fusion protein for the targeted
      delivery of SMN protein to neurons.
AB  - Spinal muscular atrophy (SMA) is a degenerative disorder of spinal motor neurons
      caused by homozygous mutations in the survival motor neuron (SMN1) gene. Because
      increased tissue levels of human SMN protein (hSMN) in transgenic mice reduce the
      motor neuron loss caused by murine SMN knockout, we engineered a recombinant SMN
      fusion protein to deliver exogenous hSMN to the cytosolic compartment of motor
      neurons. The fusion protein, SDT, is comprised of hSMN linked to the catalytic
      and transmembrane domains of diphtheria toxin (DTx) followed by fragment C of
      tetanus toxin (TTC). Following overexpression in Escherichia coli, SDT possessed
      a subunit molecular weight of approximately 130 kDa as revealed by both SDS-PAGE
      and immunoblot analyses with anti-SMN, anti-DTx, and anti-TTC antibodies. Like
      wild-type SMN, purified SDT showed specific binding in vitro to an RG peptide
      derived from Ewing's sarcoma protein. The fusion protein also bound to cultured
      primary neurons in amounts similar to those achieved by TTC. Unlike the case with
      TTC, however, immunolabeling of SDT-treated neurons with anti-TTC and anti-SMN
      antibodies showed staining restricted to the cell surface. Results from
      cytotoxicity studies in which the DTx catalytic domain of SDT was used as a
      reporter protein for internalization and membrane translocation activity suggest
      that the SMN moiety of the fusion protein is interfering with one or both of
      these processes. While these studies indicate that SDT may not be useful for SMA
      therapy, the use of the TTC:DTx fusion construct to deliver other passenger
      proteins to the neuronal cytosol should not be ruled out.

PMID- 14644475
TI  - Single-unit activity of paraventricular nucleus neurons in response to intero-
      and exteroceptive stressors in conscious, freely moving rats.
AB  - Extracellular recordings of 114 neurons in the hypothalamic paraventricular
      nucleus (PVN) of conscious, freely moving male rats were performed using a
      movable electrode system. Single-unit activities were examined for their
      spontaneous firing patterns and responses to intero- and exteroceptive stressors,
      including disturbance in arterial blood pressure, water deprivation, air-jet
      stimulation, and systemic administration of cholecystokinin-8 (CCK). PVN neurons
      were assigned to one of two groups on the basis of their spontaneous firing
      patterns: phasic (n=29) and non-phasic (n=85). Intravenous (i.v.) administration
      of phenylephrine (8 microg/kg) resulted in the inhibition of a greater percentage
      of phasic-type (88.9%; 24/27) than non-phasic-type neurons (14.9%; 11/74). Most
      phasic-type neurons showed excitation in response to i.v. administration of
      sodium nitroprusside (20 microg/kg, 66.7%; 18/27) and water deprivation (15 h,
      77.8%; 7/9) when compared to non-phasic-type neurons. Conversely, a greater
      number of non-phasic-type neurons showed excitation in response to air-jet
      stimulation (5 l/min, 10 s, 29.0%; 20/69) and to i.v. administration of CCK (5
      microg/kg, 24.5%; 11/45) when compared to phasic-type neurons. However, most non
      phasic-type neurons that demonstrated excitation in response to i.v.
      administration of CCK (88.9%; 8/9) did not respond to air-jet stimulation. The
      present study indicated that phasically firing neurons recorded from the PVN in
      conscious, freely moving rats are putative vasopressin-secreting neurons on the
      basis of their responses to intero- and exteroceptive stressors. These data
      contribute to our understanding of local neural mechanisms within the PVN that
      are responsible for stress responses in conscious rats.

PMID- 14644476
TI  - Induction of c-fos in forebrain circumventricular organs after renal artery
      stenosis.
AB  - Experiments were done in the anaesthetized rat to determine the effect of
      activation of renal receptors following renal arterial occlusion (RAO) on the
      induction of c-fos in neurons of the lamina terminalis in the forebrain.
      Following RAO, fos labeled neurons were found in both the subfornical organ (SFO)
      and the organum vasculosum of the lamina terminalis (OVLT). Transection of the
      renal nerves ipsilateral to RAO reduced ( approximately 61%) the number of fos
      labeled neurons in the SFO and prevented the fos labeling in the OVLT. Similarly,
      administration of the angiotensin II converting enzyme inhibitor enalapril
      maleate prior to RAO also reduced ( approximately 27%) the number of fos labeled
      neurons in the SFO to RAO. However, the number of fos labeled neurons was not
      altered in the OVLT. The number of fos labeled neurons in the SFO of the intact
      animals after RAO was found to be greater than the algebraic sum of the number of
      fos labeled neurons in the renal nerve transected and enalapril treated animals.
      These results suggest that neurons in the SFO are activated by at least two
      different mechanisms following renal artery occlusion; those involving the
      activation of afferent renal nerves and those due to changes in circulating
      levels of angiotensin II. In addition, afferent renal nerve inputs combined with
      the effect of increased circulating levels of angiotensin II produce a greater
      activation of the SFO than either input alone. On the other hand, the OVLT
      appears to be selectively activated by afferent renal nerve inputs following RAO.
      Taken together, these data suggest that neural inputs from the kidney may play an
      important role in controlling body fluid balance and arterial pressure (AP) by
      influencing the activity of forebrain circumventricular organs neurons that
      function in the detection of blood borne signals associated with changes in
      extracellular fluid volume.

PMID- 14644478
TI  - Non-NMDA mechanism in the inhibition of cellular apoptosis and memory impairment
      induced by repeated ischemia in rats.
AB  - The spatial memory impairment and expression of apoptotic cells in hippocampal
      CA1 cells were investigated in rats using single and repeated ischemia models.
      The neuroprotective and memory-improving effect of YM-90K, an alpha-amino-3
      hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, was compared
      to MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. Twice-repeated
      ischemia, but not single ischemia, impaired the spatial memory and increased
      expression of apoptotic cells. YM-90K, given before and 6 h after the second
      reperfusion, significantly improved the memory and reduced the apoptotic cells 7
      days after the second reperfusion in repeated ischemia. MK-801 neither improved
      the spatial memory nor reduced apoptotic cells. The present study showed that
      delayed expression of apoptotic cells is mediated by mechanisms involving AMPA
      receptors, but not by NMDA receptor, during the late phase after reperfusion. YM
      90K could provide neuroprotective activity and improve the spatial memory
      impaired by repeated ischemia.

PMID- 14644477
TI  - Glutamatergic pathways from the Kolliker-Fuse nucleus to the phrenic nucleus in
      the rat.
AB  - After ipsilateral injections of biotinylated dextran amine (BDA) into the
      Kolliker-Fuse (KF) nucleus and cholera toxin B subunit (CTb) into the ventral
      horn in C4 to C5 segments of the spinal cord, an overlapping distribution of BDA
      labeled axon terminals and CTb-labeled neurons was found in the rostral ventral
      respiratory group (rVRG) region ipsilateral to the injection sites. After
      ipsilateral injections of BDA into the KF and Fluoro-Gold (FG) into the ventral
      horn in C4 to C5 segments of the spinal cord, BDA-labeled axons were found to
      make asymmetrical synapses with the somata and dendrites of FG-labeled neurons
      within the neuropil of the rVRG region. Using retrograde tracing combined with
      immunohistochemistry for phosphate-activated glutaminase (PAG), we observed that
      as many as 72% of the rVRG neurons projecting to the PhN were immunoreactive for
      PAG and that approximately 62% and 75% of the KF neurons projecting respectively
      to the rVRG region and PhN contain PAG immunoreactivity. Using anterograde
      tracing combined with immunohistochemistry for vesicular glutamate transporter 2
      (VGluT2), we further demonstrated that the KF axon terminals in the rVRG and PhN
      regions as well as the rVRG axon terminals in the PhN region contain VGluT2
      immunoreactivity. The present results suggest that the glutamatergic pathways
      from the KF to the PhN directly and indirectly via the rVRG region may exist and
      underlie the inspiratory responses that are elicited by activation of the KF
      neurons.

PMID- 14644479
TI  - Gender- and age-specific impairment of rat performance in the Morris water maze
      following prenatal exposure to an MRI magnetic field.
AB  - We examined the effects of prenatal exposure (40 min/day, gestation days 12-18)
      of rats to a magnetic resonance imaging (MRI) magnetic field (MF) on their
      performance in the Morris water maze. At 2 months of age, female rats showed
      impaired performance. The animals spent longer time swimming and used inefficient
      strategies. However, no significant effects on maze performance were observed at
      1 and 5 months of age. No evident maze performance deficit was detected in male
      rats prenatally exposed to the magnetic field. Thus, we conclude that prenatal
      exposure to MRI magnetic field induces cognitive/behavioral deficits in female
      rats at a specific age.

PMID- 14644480
TI  - Ischemic and hemorrhagic disturbances in cerebral circulation alter contractile
      responses of the rat middle cerebral artery.
AB  - In our study, we examined middle cerebral artery (MCA) contractile responses in
      two animal models. After hemorrhagic disturbances in rats of Krushinsky-Molodkina
      strain (KMRs) a decrease in contractile responses to serotonin (5-HT) was
      observed. During incomplete global cerebral ischemia, MCAs had increased
      responsiveness to endothelin-1 (ET-1), but reduced responsiveness to serotonin.
      These findings suggest that cerebral circulation disorders alter cerebrovascular
      function possibly leading to secondary disturbances in brain circulation.

PMID- 14644481
TI  - CT-based delineation of lymph node levels and related CTVs in the node-negative
      neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines.
AB  - BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC
      requires a standardization of the procedures for the delineation of the target
      volumes. Over the past few years, two proposals--the so-called Brussels
      guidelines from Gregoire et al., and the so-called Rotterdam guidelines from
      Nowak et al.--emerged from the literature for the delineation of the neck node
      levels. Detailed examination of these proposals however revealed some important
      discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and
      Rotterdam groups decided to review their guidelines and derive a common set of
      recommendations for delineation of neck node levels. This proposal was then
      discussed with representatives of major cooperative groups in Europe (DAHANCA,
      EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional
      refinements, have endorsed them. The objective of the present article is to
      present the consensus guidelines for the delineation of the node levels in the
      node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the
      discrepancies between the previous Brussels and the Rotterdam guidelines is
      presented. The general philosophy of the consensus guidelines and the methodology
      used to resolve the various discrepancies are then described. The consensus
      proposal is then presented and representative CTVs that are consistent with these
      guidelines are illustrated on CT sections. Last, the limitations of the consensus
      guidelines are discussed and some concerns about the direct applications of these
      guidelines to the node-positive neck and the post-operative neck are described.

PMID- 14644482
TI  - Evaluation of a multimodality image (CT, MRI and PET) coregistration procedure on
      phantom and head and neck cancer patients: accuracy, reproducibility and
      consistency.
AB  - BACKGROUND AND PURPOSE: In radiotherapy planning of head and neck tumors,
      coregistration of various anatomical (e.g. CT and MRI) and functional (e.g. PET)
      images is a promising way to improve the delineation of the target volumes. In
      this paper, we report data on accuracy, reproducibility and consistency of an
      interactive coregistration procedure in a specifically designed phantom and in a
      group of patients with primary head and neck tumors. PATIENTS AND METHODS: A
      phantom and a group of four patients with pharyngo-laryngeal tumors were imaged
      by CT scan (taken as the reference image), MRI (T1- and T2-weighed sequences) and
      PET (transmission and FDG emission). Sets of images were coregistered using an
      interactive rigid coregistration method based on interactive surface
      segmentation. Translational and rotational displacements relative to the
      reference CT scan were measured and expressed in terms of accuracy,
      reproducibility (inter- and intra-observer variation) and consistency (between T1
      and T2-weighed MRI). RESULTS: Coregistration accuracy was in the range of 0.8
      6.2 mm and 1.2-4.6 mm for the phantom and the patients, respectively. Accuracy
      was slightly worse in the z direction, and was significantly correlated with the
      spatial resolution of the imaging modalities, at least for the phantom. Inter-
      and intra-observer variations were very small and always far below the residual
      variance. Consistency was perfect except in the y direction. CONCLUSION:
      Providing adequate set-up is chosen, accurate coregistration of CT, MR and FDG
      PET images can be obtained in the head and neck area. Coregistration was
      consistent and highly reproducible among observers.

PMID- 14644483
TI  - Tri-dimensional automatic segmentation of PET volumes based on measured source-to
      background ratios: influence of reconstruction algorithms.
AB  - A method for automatic volume segmentation of functional imaging based on a
      relationship between source-to-background ratio and the iso-activity level to be
      used is described. Such method, which has been established with radioactive
      spheres in a phantom, is independent of the a priori knowledge of the lesion of
      interest and is valid for small (>2 ml) and/or poorly contrasted (S/B>1.5)
      lesions. Accuracy varies slightly with the image reconstruction algorithm used.

PMID- 14644484
TI  - A comparison of forward and inverse treatment planning for intensity-modulated
      radiotherapy of head and neck cancer.
AB  - BACKGROUND AND PURPOSE: To compare intensity-modulated treatment plans of
      patients with head and neck cancer generated by forward and inverse planning.
      MATERIALS AND METHODS: Ten intensity-modulated treatment plans, planned and
      treated with a step&shoot technique using a forward planning approach, were
      retrospectively re-planned with an inverse planning algorithm. For this purpose,
      two strategies were applied. First, inverse planning was performed with the same
      beam directions as forward planning. In addition, nine equidistant, coplanar
      incidences were used. The main objective of the optimisation process was the
      sparing of the parotid glands beside an adequate treatment of the planning target
      volume (PTV). Inverse planning was performed both with pencil beam and Monte
      Carlo dose computation to investigate the influence of dose computation on the
      result of the optimisation. RESULTS: In most cases, both inverse planning
      strategies managed to improve the treatment plans distinctly due to a better
      target coverage, a better sparing of the parotid glands or both. A reduction of
      the mean dose by 3-11Gy for at least one of the parotid glands could be achieved
      for most of the patients. For three patients, inverse planning allowed to spare a
      parotid gland that had to be sacrificed by forward planning. Inverse planning
      increased the number of segments compared to forward planning by a factor of
      about 3; from 9-15 to 27-46. No significant differences for PTV and parotid
      glands between both inverse planning approaches were found. Also, the use of
      Monte Carlo instead of pencil beam dose computation did not influence the results
      significantly. CONCLUSION: The results demonstrate the potential of inverse
      planning to improve intensity-modulated treatment plans for head and neck cases
      compared to forward planning while retaining clinical utility in terms of
      treatment time and quality assurance.

PMID- 14644485
TI  - Segmental IMRT for oropharyngeal cancer in a clinical setting.
AB  - BACKGROUND AND PURPOSE: To develop a segmental intensity-modulated radiotherapy
      (IMRT) technique for the treatment of oropharyngeal cancer. PATIENTS AND METHODS:
      Eight patients previously treated for oropharyngeal cancer were replanned with
      segmental IMRT. The dose distribution was optimized using beam geometries
      consisting of 3, 5, 7 and 9 equiangular beams. The optimization procedure
      resulted in a theoretical fluence for each beam. In order to vary the number of
      segments, the optimized fluence was divided into four different equidistant
      levels. The final dose distribution was calculated using clinically deliverable
      segments obtained from optimized fluence. RESULTS: For our segmental IMRT
      technique the dose homogeneity within the target volumes improved when the total
      number of segments increased and reached a saturation level at approximately 150
      segments. Seven beams were sufficient to achieve the saturation level for dose
      homogeneity. The mean dose to the parotid glands depended on the beam geometry
      and tumor location and did not depend on the number of segments. On average the
      mean dose to the contralateral parotid gland was 35.7 Gy (27.1-39.9 Gy) for all
      seven beam plans. CONCLUSIONS: Seven beams are sufficient to achieve an
      acceptable dose homogeneity within the target volumes and significant parotid
      sparing. These results will be used to introduce IMRT in routine clinical
      practice.

PMID- 14644486
TI  - Comparative dosimetric evaluation of the simultaneous integrated boost with
      photon intensity modulation in head and neck cancer patients.
AB  - BACKGROUND AND PURPOSE: The objective of this study is to evaluate, at planning
      and dosimetric level, the potential benefits of the simultaneous integrated boost
      (SIB) concept with intensity-modulated radiation therapy (IMRT), using a
      comparative analysis on physical dose distributions corrected for radiobiological
      models. The concept of SIB at the end of the treatment has been analysed as an
      alternative acceleration scheme. PATIENTS AND METHODS: Physical dose
      distributions were computed on a commercial planning system (Varian Cadplan
      Helios) for five patients presenting with advanced head and neck carcinomas.
      Treatment plans were designed using five IMRT beams. Three fractionation
      strategies were compared in the study: the standard sequential irradiation SEQ of
      elective and boost volumes, the pure SIB, and a modified SIB (SEQ/SIB), where the
      actual SIB follows a first phase of conventional fractionation to the elective
      volume. All physical dose distributions were corrected using a linear quadratic
      biological model, taking into account also repopulation and time at repopulation
      onset. Objective quantities, derived from biological dose volume histograms, were
      used for the analysis. RESULTS: Physical doses equivalent to 50 and 80 Gy (in
      fractions of 2 Gy) to elective volume and boost were calculated for the SIB and
      SEQ/SIB regimes. With SIB 54 and 72 Gy dose levels have to be delivered in 30
      fractions, while in the SEQ/SIB scheme 36 Gy are delivered in 20 sessions to the
      elective volume, and further 18 and 35.5 Gy during the last 10 fractions are
      delivered to elective volume and boost, respectively (for a total physical dose
      of 71.5 Gy). The comparison showed: (1) the boost target homogeneity resulted in
      generally acceptable and comparable among sequential and modified SIB schemes,
      while it was statistically worse for the pure SIB approach; (2) the fraction of
      elective target volume not included in the boost volume was characterised by a
      higher level of dose heterogeneity; (3) the spinal cord never reached tolerance
      levels and maximum point dose was on average below 38 Gy (biologically corrected
      to 2 Gy/fraction); and (4) sparing of parotid glands strongly depends on their
      eventual inclusion in the target volumes: for glands not included or only
      partially included, it was possible on average to keep the dose to 2/3 of the
      volume below 29 Gy for all regimes (32 Gy as physical dose). CONCLUSIONS:
      Feasibility of SIB techniques and in particular of the modified SIB appears to be
      dosimetrically proven and the results reported here justify the activation of a
      phase I protocol to verify clinically their impact using IMRT photon-based
      techniques.

PMID- 14644487
TI  - Breast-conserving surgery has equivalent effect as mastectomy on stage I breast
      cancer prognosis only when followed by radiotherapy.
AB  - BACKGROUND AND PURPOSE: Early-stage breast cancer is increasing and consequently
      the use of breast-conserving surgery (BCS). We examined the effect of mastectomy
      and BCS on overall and breast cancer survival in routine health care in Geneva,
      Switzerland. PATIENTS AND METHODS: We included all stage I breast cancers treated
      by surgery (n=1046) recorded at the Geneva Cancer Registry between 1988 and 1999.
      The effect of treatment type was evaluated by Cox models, which accounted for
      confounders. RESULTS: Overall, 780 (75%) women had BCS with radiotherapy, 57 (5%)
      BCS alone and 209 (20%) mastectomy. The overall 10-year survival was 86, 56, and
      72%, respectively. The effect of BCS with radiotherapy was similar to that of
      mastectomy for both breast cancer mortality (adjusted hazard ratio (HR), 0.67;
      95%CI, 0.31-1.38) and other causes of mortality (HR, 0.79; 95%CI, 0.49-1.28).
      Women with BCS alone had higher mortality from breast cancer (HR, 3.95; 95%CI,
      1.59-9.84). CONCLUSIONS: This retrospective study shows that BCS plus
      radiotherapy is the predominant treatment in routine practice for stage I breast
      cancer in Geneva, with the same effect on survival as mastectomy. In this data
      set the addition of radiotherapy to BCS substantially reduces mortality from
      breast cancer without increasing other causes of mortality after 10 years of
      follow-up.

PMID- 14644488
TI  - In vivo dosimetry using radiochromic films during intraoperative electron beam
      radiation therapy in early-stage breast cancer.
AB  - BACKGROUND AND PURPOSE: To check the dose delivered to patients during
      intraoperative electron beam radiation therapy (IOERT) for early breast cancer
      and also to define appropriate action levels. PATIENTS AND METHODS: Between
      December 2000 and June 2001, 54 patients affected by early-stage breast cancer
      underwent exclusive IOERT to the tumour bed using a Novac7 mobile linac, after
      quadrantectomy. Electron beams (5, 7, 9 MeV) at high dose per pulse values (0.02
      0.09 Gy/pulse) were used. The prescribed single dose was 21 Gy at the depth of
      90% isodose (14-22 mm). In 35 cases, in vivo dosimetry was performed. The
      entrance dose was derived from the surface dose measured with thin and calibrated
      MD-55-2 radiochromic films, wrapped in sterile envelopes. Films were analysed 24
      72 h after the irradiation using a charge-coupled-device imaging system. Field
      disturbance caused by the film envelope was negligible. RESULTS: The mean
      deviation between measured and expected doses was 1.8%, with one SD equal to
      4.7%. Deviations larger than 7% were found in 23% of cases, never consecutively,
      not correlated with beam energy or field size and with no evidence of linac daily
      output variation or serious malfunctioning or human mistake. The estimated
      overall uncertainty of dose measurement was about 4%. In vivo dosimetry appeared
      both reliable and feasible. Two action levels, for unexplained observed
      deviations larger than 7 and 10%, were preliminary defined. CONCLUSIONS:
      Satisfactory agreement between measured and expected doses was found. The
      implementation of in vivo dosimetry in IOERT is suggested, particularly for
      patients enrolled in a clinical trial.

PMID- 14644489
TI  - Organ motion, set-up variation and treatment margins in radical radiotherapy of
      urinary bladder cancer.
AB  - BACKGROUND AND PURPOSE: A major challenge in conformal radiotherapy of bladder
      cancer is to determine adequate treatment margins. For this purpose, we therefore
      quantified the internal motion of the urinary bladder as well as the external
      patient set-up variation during a course of fractionated radiotherapy. In the
      light of the recently introduced ICRU-62 concept, the planning organ at risk
      volume, we also studied the internal motion of nearby organs at risk, the rectum
      and intestine. MATERIAL AND METHODS: Weekly CT scans and electronic portal images
      (EPIs) were sampled from 20 patients during radical, conformal bladder
      irradiation (60-64 Gy/2 Gy in five fractions weekly). The planning scans were
      acquired with 70 ml of bladder contrast instilled, and patients were instructed
      to void before the treatment/repeat scanning sessions. Internal motion of the
      bladder, rectum and intestine was measured by 3-D image matching of the repeat
      scans to the patients' planning scans. Internal margins (CTV-to-ITV) were
      determined using both a direct empirical approach and an analytically derived
      margin recipe. The external patient set-up variability was determined by 2-D
      matching of front and lateral EPIs to corresponding digitally reconstructed
      radiographs. RESULTS: A total of 149 CT scans (20 for planning, 129 during the
      treatment course) and 133 sets of EPIs were analysed. Bladder volumes were
      smaller during treatment than in the planning situation in 85% of the repeat
      scans. Nevertheless, we found the repeat scan bladder volumes to extend outside
      the planning scan bladder contours in 89% of the scans, on average with 9% of the
      volume (range: 0-47%). Eight patients (40%) had at least one repeat scan (25
      scans in total) where displacements >15 mm were observed at one or more sides of
      the bladder. CTV-to-ITV margins of 10 mm inferior, 20 mm superior, 11 mm left, 8
      mm right, 20 mm anterior and 14 mm posterior were required to simultaneously
      encompass all bladder deflections except for the largest outward deflection in
      all directions in 84% of the patients. Including patient set-up variation (CTV-to
      PTV), we found that an additional safety margin of 2-6 mm had to be added in the
      various directions. The rectum expanded outside the planning contours in all
      repeat scans, on average with 24% of the volume (range: 2-69%). The volume of
      intestine found close to the bladder were significantly and negatively correlated
      to the bladder volume in almost half of the patients. CONCLUSION: This study
      documented both a large internal motion of the bladder and a substantial patient
      set-up variation. Our current treatment margins have been adjusted according to
      the findings of this study. Considerable variation in position and volume of the
      rectum and intestine was also documented.

PMID- 14644490
TI  - Importance of accurate dose calculations outside segment edges in intensity
      modulated radiotherapy treatment planning.
AB  - BACKGROUND AND PURPOSE: To assess the effect of differences in the calculation of
      the dose outside segment edges on the overall dose distribution and the
      optimisation process of intensity modulated radiation therapy (IMRT) treatment
      plans. PATIENTS AND METHODS: Accuracy of dose calculations of two treatment
      planning systems (TPS1 and TPS2) was assessed, to ensure that they are both
      suitable for IMRT treatment planning according to published guidelines.
      Successively, 10 treatment plans for patients with prostate and head and neck
      tumours were calculated in both systems. The calculations were compared in
      selected points as well as in combination with volumetric parameters concerning
      the planning target volume (PTV) and organs at risk. RESULTS: For both planning
      systems, the calculations agree within 2.0% or 3 mm with the measurements in the
      high-dose region for single and multiple segment dose distributions. The accuracy
      of the dose calculation is within the tolerances proposed by recent
      recommendations. Below 35% of the prescribed dose, TPS1 overestimates and TPS2
      underestimates the measured dose values, TPS2 being closer to the experimental
      data. The differences between TPS1 and TPS2 in the calculation of the dose
      outside segments explain the differences (up to 50% of the local value) found in
      point dose comparisons. For the prostate plans, the discrepancies between the TPS
      do not translate into differences in PTV coverage, normal tissue complication
      probability (NTCP) values and results of the plan optimisation process. The dose
      volume histograms (DVH) of the rectal wall differ below 60 Gy, thus affecting the
      plan optimisation if a cost function would operate in this dose region. For the
      head and neck cases, the two systems give different evaluations of the DVH points
      for the PTV (up to 22% differences in target coverage) and the parotid mean dose
      (1.0-3.0 Gy). Also the results of the optimisation are influenced by the choice
      of the dose calculation algorithm. CONCLUSIONS: In IMRT, the accuracy of the dose
      calculation outside segment edges is important for the determination of the dose
      to both organs at risks and target volumes and for a correct outcome of the
      optimisation process. This aspect should therefore be of major concern in the
      commissioning of a TPS intended for use in IMRT. Fulfilment of the accuracy
      criteria valid for conformal radiotherapy is not sufficient. Three-dimensional
      evaluation of the dose distribution is needed in order to assess the impact of
      dose calculation accuracy outside the segment edges on the total dose delivered
      to patients treated with IMRT.

PMID- 14644491
TI  - Computer optimization of class solutions designed on a beam segmentation basis.
AB  - BACKGROUND AND PURPOSE: A method for analytically solving the optimization of
      beam weighting in radiotherapy treatments using beam segmentation is presented.
      PATIENTS AND METHODS: A technique has been elaborated permitting the optimization
      of a flexible objective function which is defined by considering 'importance
      factors' for each anatomical region and 'allowed deviations' from the prescribed
      dose. As any change in these importance factors may lead to very different
      solutions, a statistical tool has been developed which varies the objective
      function automatically and iteratively to get the best possible results
      compatible with the chosen class solution. In addition, the spatial symmetry
      found in many anatomical sites is taken advantage of. Furthermore, freeware code
      has been written to run this optimization approach. The guidelines to design the
      beam segmentation used in our institution using organ avoidance criteria, and
      hence the suitable class solution for different anatomical sites, are given. A
      treatment-planning study for three anatomical sites is presented and, for two of
      them, the results obtained with both the suggested and the classical inverse
      approach are presented. RESULTS: The work presented might be used for beam
      weighting optimization in any radiotherapy treatment and furthermore, the
      suggested procedure may successfully confront the intensity-modulated radiation
      therapy (IMRT) problem and the obtained dose distributions fit the clinical
      constraints for all anatomical sites studied. When comparing with the classical
      inverse approach, both results are comparable in terms of dose distribution, but
      the suggested technique reduces the integral dose as the total number of monitor
      units is lower. CONCLUSIONS: The developed code performs the optimization with a
      very low time cost and in addition, this process can be carried out with a
      conventional treatment-planning system with no need of dedicated IMRT software.

PMID- 14644492
TI  - Thallium-201-chloride scintigraphy in staging and monitoring radiotherapy
      response in follicular lymphoma patients.
AB  - PURPOSE: To study thallium-201-chloride scintigraphy (201Tl-S) in staging and
      monitoring response after radiotherapy in follicular lymphoma (FL) patients.
      PATIENTS AND METHODS: Forty-one consecutive and unselected FL patients were
      examined by 'Conventional Standard Staging' (CSS) procedures (history and
      physical examination, ultrasound, CT scans, biopsies and fine needle aspiration
      cytology) prior to irradiation. Eight standardized potentially affected lymphoma
      localizations (neck, axilla, mediastinum, spleen, paraaortic, parailiac, femoral
      and extranodal) per patient were separately studied, resulting in the
      investigation of 328 localizations. Thirty minutes after the intravenous
      administration of a tracer dose of 150 MBq thallium-201-chloride total body
      images were made, immediately followed by single photon emission computed
      tomography acquisition. All lymphoma localizations were subsequently irradiated.
      Patients were re-examined after a median of 4 weeks (range 3-6 weeks) by all CSS
      modalities and 201Tl-S. Diagnostic performance was evaluated both per site and
      per patient, both in the diagnostic phase of the study as well as in the post
      treatment re-evaluation phase. RESULTS: In staging, 201Tl-S was positive in 82 of
      the 129 initial positive regions by CSS (64%). This percentage increased to 70%
      when eliminating upper abdominal lymph nodes from the analysis. In 24 patients
      all lesions were visualized by 201Tl-S, in 11 patients some but not all lesions
      were detected. In six patients none of the lesions were detected by 201Tl-S. In
      four patients, four additional lesions were initially found by 201Tl-S only.
      After irradiation, 83 of the total 86 positive regions reached a complete or
      partial remission by CSS. Eighty-one of these were also diagnosed as remission by
      201Tl-S and two as stable disease. In 31 out of 35 patients (89%; 95% CI: 73-97%)
      the overall response in all irradiated sites was identical by 201Tl-S and CSS.
      Only two patients, in remission on CSS modalities, showed stable disease on 201Tl
      S, while two others were diagnosed as CR by CSS and PR by 201Tl-S. CONCLUSIONS:
      201Tl-S has limited additional value in staging FL patients, since only two
      thirds of all localizations are detected. However, 201Tl-S is accurate in
      monitoring radiation treatment response in FL patients. If an FL patient with a
      positive 201Tl-S at diagnosis is treated by irradiation, the treatment response
      can be reliably ascertained by only performing a 201Tl-S.

PMID- 14644493
TI  - DNase II: genes, enzymes and function.
AB  - Deoxyribonuclease (DNase) II, which was discovered more than 50 years ago, is a
      mammalian endonuclease that functions optimally at acid pH in the absence of
      divalent cations. Its lysosomal localization and ubiquitous tissue distribution
      suggested that this enzyme played a role in the degradation of exogenous DNA
      encountered by phagocytosis, although the relative importance of such a role was
      unknown. Subsequent investigations also suggested that DNase II was important for
      DNA fragmentation and degradation during cell death. Within the last few years,
      our work and that of others has lead to the cloning of various mammalian DNase II
      genes as well as the identification and characterization of highly homologous
      genes in the invertebrates Caenorhabditis elegans and Drosophila melanogaster.
      Interestingly, studies of the C. elegans DNase II homolog NUC-1 were the first to
      suggest that DNase II enzymes were fundamentally important in engulfment-mediated
      DNA degradation, particularly that associated with programmed cell death, due to
      the presence of persistent apoptotic-cell nuclei within phagocytic cells in nuc-1
      mutants. Similarly, mutation of the Drosophila DNase II-like gene was found to
      result in the accumulation of low-molecular-weight DNA throughout the animals.
      Homozygous mutation (knockout) of the DNase II gene in mice revealed a much more
      complex and extensive phenotype including perinatal lethality. The lethality of
      DNase II-knockout mice is likely the result of multiple developmental defects,
      the most obvious being a loss of definitive erythropoiesis. Closer examination
      revealed that a defect in engulfment-mediated DNA degradation is the primary
      defect in DNase II-null mice. In this review, we have compiled information from
      studies on DNase II from various organisms to provide a consensus model for the
      role of DNase II enzymes in DNA degradation.

PMID- 14644494
TI  - Organization and evolution of multifunctional Ca(2+)/CaM-dependent protein kinase
      genes.
AB  - The "multi-functional" Ca(2+) and calmodulin-dependent protein kinase, type II
      (CaMK-II) is an evolutionarily conserved protein. It has been found as a single
      gene in the horseshoe crab, marine sponge, sea urchin, nematode, and fruit fly,
      whereas most vertebrates possess four genes (alpha, beta, gamma, and delta).
      Species from fruit flies to humans encode alternative splice variants which are
      differentially targeted to phosphorylate diverse downstream targets of Ca(2+)
      signaling. By comparing known CaMK-II protein and nucleotide sequences, we have
      now provided evidence for the evolutionary relatedness of CaMK-IIs. Parsimony
      analyses unambiguously indicate that the four vertebrate CaMK-II genes arose via
      repeated duplications. Nucleotide phylogenies show consistent but moderate
      support for the placement of the vertebrate delta CaMK-II as the earliest
      diverging vertebrate gene. delta CaMK-II is the only gene with both central and C
      terminal variable domains and has three to four times more intronic sequence than
      the other three genes. beta and gamma CaMK-II genes show strong sequence
      similarity and have comparable exon and intron organization and utilization.
      alpha CaMK-II is absent from amphibians (Xenopus laevis) and has the most
      restricted tissue specificity in mammals, whereas beta, gamma, and delta CaMK-IIs
      are expressed in most tissues. All 38 known mammalian CaMK-II splice variants
      were compiled with their tissue specificity and exon usage. Some of these
      variants use alternative 5' and 3' donors within a single exon as well as
      alternative promoters. These findings serve as an important benchmark for future
      phylogenetic, developmental, or biochemical studies on this important, conserved,
      and highly regulated gene family.

PMID- 14644495
TI  - Chromatin remodeling during sea urchin early development: molecular determinants
      for pronuclei formation and transcriptional activation.
AB  - Transcriptional activation of specific genes is initiated after fertilization by
      the interaction of specific transcription factors with its cognate sequences in
      the chromatin context, thereby leading to a concerted and coordinated program
      which determines early development. Remodeling of the sperm chromatin after
      fertilization is a fundamental event for transcriptional activation and
      expression of the paternally inherited genome. The transitions in chromosomal
      proteins, as well as the mechanisms that participate in these transitions, have
      been investigated only to a limited extent as compared to the signal transduction
      patterns that govern egg activation or the dynamics and structural changes
      accompanying sperm nuclear membrane dissociation-association following
      insemination. In this review, we will discuss the remodeling of sperm chromatin
      that follows fertilization. We will emphasize the transitions of chromosomal
      proteins, as well as the post-translational modifications associated with these
      transitions. The molecular mechanisms that may be participating in these events
      will also be analyzed. We will further discuss the mechanisms that govern
      chromatin remodeling and the role of specific transcription factors in the
      control of the transcriptional program during sea urchin early development.

PMID- 14644496
TI  - Identification of a novel proliferation-dependent C-rich element that mediates
      inhibition of the rat GLUT1 promoter.
AB  - Expression of the glucose transporter GLUT1 is high in proliferating and tumour
      cells. Conditions in which the transcriptional activity of GLUT1 promoter are
      maximal are characterized by the operation of activators such as Sp1 and
      inhibitors as Sp3. Here, we have identified an element at -67/-60 (C8 box) in the
      rat GLUT1 promoter to which nuclear factors bind in a proliferation-dependent
      manner. Competition studies with a series of mutated oligonucleotides suggest
      that these nuclear factors are different in the proliferative state and after
      confluence. The C8 element does not bind any of the known factors defined in
      databases. Mutation of the C8 sequence enhanced transcriptional activity of the
      GLUT1 promoter in 10T1/2 fibroblasts and in L6E9 myoblasts but not in myotubes.
      Furthermore, the functional activity of the C8 box is maximal in the presence of
      serum. In summary, we have identified a novel inhibitory element, C8 box, in the
      rat GLUT1 promoter that operates in a proliferation-dependent manner. In keeping
      with this view, serum enhances the inhibitory activity of the C8 box, suggesting
      that this is regulated by growth factors.

PMID- 14644497
TI  - Transposon-mediated enhancer trapping in medaka.
AB  - We tested the Sleeping Beauty transposable element for its ability to efficiently
      insert transgenes into the genome of medaka (Oryzias latipes), an important model
      system for vertebrate development. We show that the SB transposon efficiently
      mediates integration of a reporter gene into the fish germ line. In pilot
      experiments, we established 174 transgenic lines with a transgenesis efficiency
      of 32%. Transgenes are stably transmitted to, and expressed in, subsequent
      generations. Interestingly, the transgenic lines show novel expression patterns
      with temporal and spatial specificity at a rate of 12% (21/174), likely due to
      both, enhancing and silencing position effects. Furthermore, promoter-dependent
      GFP expression in injected fish embryos is tightly correlated with germ line
      transmission, facilitating easy selection of founder fish. Thus, the SB
      transposon/transposase system provides a highly efficient tool for transgenesis
      in general and for the generation of novel reporter gene expression patterns in
      particular.

PMID- 14644498
TI  - Complete nucleotide sequence of the circular megaplasmid pHCG3 of Oligotropha
      carboxidovorans: function in the chemolithoautotrophic utilization of CO, H(2)
      and CO(2).
AB  - Oligotropha carboxidovorans harbors the low-copy-number, circular, 133,058-bp DNA
      megaplasmid pHCG3, which is essential in the chemolithoautotrophic utilization of
      CO (carboxidotrophy), H(2) (hydrogenotrophy) and CO(2) under aerobic conditions.
      The complete nucleotide sequence of pHCG3 revealed 125 open reading frames. Of
      these, 95 were identified as putative structural genes. The plasmid carries the
      four gene clusters cox (14.54 kb, 12 genes), cbb (13.33 kb, 13 genes), hox (23.35
      kb, 19 genes plus one ORF) and tra/trb (25.01 kb, 22 genes plus 2 ORFs), which
      assemble the functions required for the utilization of CO, CO(2) or H(2), and the
      conjugal transfer of the plasmid, respectively. The gene clusters cox, cbb and
      hox form a 51.2-kb chemolithoautotrophy module. The tra/trb cluster on the
      plasmid pHCG3 of O. carboxidovorans has a similar architecture as the Ti-plasmid
      of Agrobacterium tumefaciens. The tra/trb cluster is separated from the
      chemolithoautotrophy module by two regions (25.2 and 29.6 kb) with miscellaneous
      or mostly unknown functions. These regions carry a number of single genes coding
      for replication and stabilization of pHCG3 as well as the components of a
      putative system of global regulation of plasmid replication in O.
      carboxidovorans. An oriV encodes the replication proteins RepABC. Sequence
      comparisons of pHCG3-encoded genes suggest that major genetic exchange between O.
      carboxidovorans and the proteobacteria has occurred.

PMID- 14644499
TI  - Structure, expression, and cluster organization of genes encoding gonadotropin
      releasing hormone receptors found in the neural complex of the ascidian Ciona
      intestinalis.
AB  - Gonadotropin-releasing hormone (GnRH) controls reproductive functions in
      vertebrates. In the present study, two distinct homologues (Ci-GnRHR1 and Ci
      GnRHR2) of the vertebrate GnRH receptor (GnRHR) were identified by cDNA cloning
      from the neural complex of the ascidian Ciona intestinalis. The Ci-GnRHR1 and Ci
      GnRHR2 genes are closely linked to each other and form a cluster with another
      GnRHR-like gene in the genome. Ci-GnRHR1 and Ci-GnRHR2 are more closely related
      to vertebrate GnRHRs than to the GnRHR-related protein of Drosophila. The
      phylogenetic analysis indicates that vertebrates and urochordates independently
      acquired multiple GnRHRs by gene duplications that occurred during the evolution
      of each lineage. A voltage clamp of Xenopus oocytes injected with synthetic Ci
      GnRHR1 mRNA revealed inward currents in response to an ascidian form of GnRH,
      suggesting that Ci-GnRHR1 is a bona-fide GnRHR. Expression patterns of Ci-GnRHR1
      and Ci-GnRHR2 suggest that a GnRH signaling system is involved in regulation of
      neuronal and reproductive processes as well as in other physiological functions
      in ascidians.

PMID- 14644500
TI  - Identification and characterization of simple sequence repeats in the genomes of
      Shigella species.
AB  - A variety of simple sequence repeats (SSRs) have been identified in the genome of
      Shigella flexneri serotype 2a (strain Sf301), an enteric pathogen that causes
      bacillary dysentery in man. The distribution of SSRs, with unit length ranging
      from 1 to 9 nucleotides, was biased in different regions of the genome. The tri-,
      tetra- and hexanucleotide SSRs prevailed in the coding regions while the mono-
      and dinucleotide SSRs were more common in the noncoding regions. Many intergenic
      SSRs are less than 30 bp away from the downstream open reading frames (ORFs),
      suggesting a potential role in transcriptional regulation. To study polymorphism
      of SSRs, we compared 17 coding-region SSRs from strain Sf301 with the
      corresponding sequences from 23 other strains of four Shigella species. Five
      chromosomal loci were found to be polymorphic, of which those from S. flexneri
      strains were most variable. Particularly interesting is the C5-1 locus in the
      coding sequence of the hcaD gene encoding a subunit of ferredoxin reductase.
      Depending on the insertion of variable numbers of the unit sequence (CGCAG), the
      Shigella hcaD genes can encode truncated products due to premature stop codons or
      frame shifts, or products with extended core alpha helices that leads to radical
      alterations in the predicted tertiary structure. Hence, SSRs may serve as
      genotyping markers for epidemiological investigations, and may offer insights
      into evolutionary adaptation of the pathogens.

PMID- 14644501
TI  - Importance of ascorbate peroxidases OsAPX1 and OsAPX2 in the rice pathogen
      response pathways and growth and reproduction revealed by their transcriptional
      profiling.
AB  - We have identified and characterized two rice ascorbate peroxidase (OsAPX1 and
      OsAPX2) genes against diverse signals known to involve in defense/stress
      responses, using "2-week-old rice seedling in vitro model system". Oryza sativa
      ascorbate peroxidase 1 and 2 (OsAPX1/2) share 83% similarity to each other at
      amino acid level and belong to a small gene family in the rice genome. OsAPX1/2
      show a weak constitutive expression in leaves. Their transcripts were up
      regulated upon wounding (by cut), and diverse signals such as salicylic acid
      (SA), ethylene (using the ethylene generator, ethephon), abscisic acid (ABA),
      hydrogen peroxide, copper sulfate, protein phosphatase (PP) inhibitors,
      cantharidin (CN), endothall (EN) and okadaic acid (OA), and blast pathogen
      (Magnaporthe grisea) attack, but surprisingly not by jasmonic acid (JA).
      Interestingly, the OsAPX2 inductions were more potent and rapid than OsAPX1,
      whose expression increased gradually with time. These inductions were influenced
      by light signal(s), and showed requirement for certain de novo synthesized
      protein factor(s). Intriguingly, OsAPX1/2 mRNAs expression manifested a clear
      rhythmicity under light/dark cycle. Differential regulation of the OsAPX1/2
      expressions by diverse environmental cues, including pathogen, and their
      developmental regulation in both young and reproductive stages strongly suggests
      their role in stress-signaling pathways and development in rice.

PMID- 14644502
TI  - Cloning and characterization of Xenopus laevis drg2, a member of the
      developmentally regulated GTP-binding protein subfamily.
AB  - The developmentally regulated GTP-binding protein (DRG) subfamily is an
      uncharacterized member of the Obg family, an evolutional branch of GTPase
      superfamily proteins. GTPases act as molecular switches regulating diverse
      cellular processes. DRG2 and DRG1 comprise the DRG subfamily in eucaryotes.
      Although drg1 was first identified as a gene predominantly expressed during early
      development of the mouse central nervous system, comparative analysis of drg2 and
      drg1 expression during embryogenesis has never been reported, and the biochemical
      properties of the DRG family proteins remain to be elucidated. Thus, we first
      cloned Xenopus drg2 (Xdrg2) and examined the temporal and spatial expression
      patterns of Xdrg2 mRNA in comparison to those of Xdrg1. Both Xdrg2 and Xdrg1 are
      induced at late gastrula and subsequently increased during later stages of
      embryos (stage 13-41). Whole-mount in situ hybridization showed that Xdrg2 and
      Xdrg1 expression patterns are almost identical except that only Xdrg2 expression
      is detected in the stage 22 pronephric anlage. Strong transcripts of both genes
      are also observed at this stage in neural crest cells, blood islands, and
      developing eyes, and in brain, eyes, otic vesicle, branchial arches,
      pronephroses, spinal cord, notochord, head mesenchyme, and somites at stages 27
      and 32. Northern blot analysis of adult tissues revealed that both genes are
      expressed highly in ovary and testis and rather moderately in other organs,
      except that Xdrg1 transcripts are scarcely detected in heart, lung, and liver.
      Accordingly, transcription or stability of Xdrg2 and Xdrg1 mRNAs may be regulated
      by different mechanisms. In addition, by generating recombinant XDRG2 and XDRG1
      proteins, we found the RNA binding activity of these proteins in vitro. Our
      results suggest that the DRG proteins may play their physiological roles via RNA
      binding.

PMID- 14644503
TI  - Characterization of the role of Sp1 and NF-Y in differential regulation of
      PTTG/securin expression in tumor cells.
AB  - Pituitary tumor transforming gene (PTTG), also known as securin, is a regulator
      of cell division that is overexpressed in many tumors. Its expression is cell
      cycle regulated, although its transcriptional regulation is yet to be determined.
      The 5' RACE analysis of the human testis mRNA revealed the existence of a
      previously unreported transcription start site at 317 bp upstream of the
      translation start site (ATG). This gene is known to be composed of five exons and
      four introns, which is now changed to six exons and five introns. To map the
      promoter region, and to understand its regulation, we designed several fusion
      constructs of the 5' flanking region of PTTG including the sequence from
      nucleotide -1373 to -3 (relative to the translation start site) to a luciferase
      reporter gene. Transient transfection of these constructs in prostate cancer cell
      line (PC-3) and fibroblast cell line (HS27) confirmed the existence of promoter
      for PTTG between nucleotides -161 and -3 (in relation to translation start site).
      The 5' and 3' deletion analysis of the PTTG flanking region and electrophoretic
      mobility shift assays revealed binding of Sp1 and NF-Y transcription factors
      within nucleotides -540 to -500. Chromatin immunoprecipitation (ChIP) assays of
      the HS27 and PC-3 cells revealed the binding of Sp1 protein to PTTG promoter
      sequence in vivo. Site-directed mutagenesis of the Sp1 consensus sequence
      resulted in approximately 70% reduction of the overall transcriptional activation
      of the PTTG promoter, whereas mutation of the NF-Y sequence resulted in
      approximately 25% reduction. Deletion of both Sp1 and NF-Y consensus sequences
      resulted in 90% loss of PTTG promoter activity. It was further observed, by
      Western blot analysis, that the levels of Sp1 protein are higher in PC-3 cells
      when compared to levels in HS27 cells, possibly contributing to a tissue-specific
      effect. Our studies indicate an important role of Sp1 in transcription regulation
      of PTTG expression in tumors.

PMID- 14644504
TI  - Analysis of the rat connexin 43 proximal promoter in neonatal cardiomyocytes.
AB  - Altered transcriptional control is likely to contribute to the down-regulation of
      connexin 43 (Cx43) expression observed in many forms of heart disease. However,
      little is known about the factors regulating Cx43 transcription in the heart
      under (patho)physiological conditions. Therefore, a systematic study of rat Cx43
      (rCx43) proximal promoter regulation in rat primary neonatal ventricular
      cardiomyocytes (NCM) and, for comparison, different cell types was initiated.
      Luciferase assays revealed that, in NCM, the proximal promoter is preserved in a
      conserved region extending from 148 nucleotides upstream towards 281 nucleotides
      downstream relative to the transcription initiation site (TIS). Further
      deletional analysis suggested the involvement of four putative Sp- and two AP1
      binding sites. The binding of both Sp1 and Sp3 to the Sp-binding elements and AP1
      to the AP1-binding elements was demonstrated by electrophoretic mobility shift
      assays (EMSA). Promoter-luciferase assays using the natural rCx43 proximal
      promoter and mutated derivatives in NCM, HL-1 and A7r5 cells revealed that all
      sites contribute to basal promoter activity. Trans-activation of the Cx43
      proximal promoter with Sp1 and Sp3 in Drosophila Schneider line 2 (SL2) cells
      demonstrated that Sp1 and, to a lesser extent, Sp3 determine rCx43 promoter
      activation. Thus Sp1, Sp3 and AP1 determine basal Cx43 expression. In addition,
      we studied the effect of the cardiac transcription factor Nkx2.5 on Cx43
      regulation. NCM were infected with adenovirus encoding either beta-galactosidase
      (control) or Nkx2.5. Cx43 protein and mRNA were significantly decreased after
      Nkx2.5 infection as shown by Western and Northern blot analyses. Promoter
      reporter assays demonstrated that the rCx43 promoter was down-regulated
      approximately twofold upon Nkx2.5 overexpression. Therefore, in NCM, Nkx2.5
      appears to play a role in the regulation of Cx43 expression.

PMID- 14644505
TI  - Chimeric transcriptional control units for improved liver-specific transgene
      expression.
AB  - Hepatocyte-directed delivery of therapeutic genes is a major field of gene
      therapy. An important issue in this context is the availability of promoters
      units providing for maximum transcriptional activity and specificity. Although a
      number of liver-specific promoters and transcriptional control elements have been
      identified and used for gene delivery, no systematic study has been performed to
      identify the best suitable combination of known liver-specific promoter and
      enhancer elements. We now report the results of a comparative investigation
      addressing this issue. We tested a total of 25 synthetic transcriptional control
      units consisting of either of the four core promoters from liver-specific genes
      linked in various combinations and configurations to hepatocyte-specific enhancer
      elements. These constructs were analyzed for transcriptional activity in
      different cell types in cell culture and in mouse liver in vivo. The data lead to
      the clear conclusion that a combination of the alcohol dehydrogenase 6 (ADH6)
      basal promoter linked to two tandem copies of an apoplipoprotein E enhancer
      element is the transcriptional control unit of choice for the liver-specific
      expression of transgenes.

PMID- 14644506
TI  - Common carp insulin-like growth factor-I gene: complete nucleotide sequence and
      functional characterization of the 5'-flanking region.
AB  - Insulin-like growth factor-I (IGF-I) plays an important role in the growth and
      development of fish. To understand the molecular mechanism which controls the
      transcription of the IGF-I gene in common carp, we have cloned and completely
      sequenced the IGF-I gene and the 5'-flanking region from a local tropical fish,
      the common carp (Cyprinus carpio), and characterized its promoter activity by
      transfection into human embryonic kidney (293GHR) cells which express the human
      growth hormone (GH) receptor. The common carp gene is the smallest IGF-I gene
      known so far, spanning approximately 13 kb, and is consisted of five exons and
      four introns. The sequence of the gene is consistent with the single type of IGF
      I cDNA that we have isolated previously from a common carp liver cDNA library.
      The expression pattern of IGF-I is similar between juvenile carp and adult carp.
      While liver was found to be the major site of IGF-I gene expression in common
      carp, the expression levels in other tissues are relatively low. Like many other
      IGF-I gene promoters, there are no apparent TATA box and CCAAT box upstream of
      the transcription initiation site. However, sequence analysis of the common carp
      IGF-I promoter region identified several consensus liver-enriched transcription
      factor binding sites, including HNF-1alpha, HNF-3beta, C/EBP, and one STAT5. We
      have analyzed the promoter activity of the 5'-flanking region of the common carp
      IGF-I gene by performing luciferase reporter assays in transfected 293GHR cells.
      Addition of human GH to the transfected cells led to an increased expression of
      the reporter gene, indicating that the cloned genomic fragment possessed promoter
      activity. This was confirmed by the lack of promoter activity of a construct in
      which the putative promoter was cloned in a reverse orientation upstream of the
      reporter gene. The liver-specific transcription factor, hepatic nuclear factor
      (HNF)-1alpha, was also found to be involved in the regulation of the common carp
      IGF-I transcription. Transfection results from a set of deletion mutants helped
      to map the locations of the responsive elements on the promoter responsible for
      the GH effect and for the interaction with HNF-1alpha. These observations provide
      information for delineating the transcriptional regulation of IGF-I gene
      expression in common carp.

PMID- 14644507
TI  - The lethal phenotype observed after HIV-1 integrase expression in yeast cells is
      related to DNA repair and recombination events.
AB  - Human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalyzes the
      insertion of the viral genome into the host cell DNA, an essential reaction
      during the retroviral cycle. We described previously that expression of HIV-1 IN
      in some yeast strains may lead to the emergence of a lethal phenotype which was
      not observed when the catalytically crucial residues D, D, (35)E were mutated.
      The lethal effect in yeast seems to be related to the mutagenic effect of the
      recombinant HIV-1 IN, most probably via the non-sequence-specific endonucleolytic
      activity carried by this enzyme. This non-sequence-specific endonuclease activity
      was further characterized. Although the enzyme was active on DNA substrates
      devoid of viral long terminal repeat (LTR) sequences, the presence of LTR regions
      stimulated significantly this activity. Genetic experiments were designed to show
      that both the mutagenic effect and the level of recombination events were
      affected in cells expressing the active retroviral enzyme, while expression of
      the mutated inactive IN D116A has no significant effect. A close interaction was
      demonstrated between integrase activity and in vivo/in vitro recombination
      process, suggesting that retroviral integration and recombination mechanism are
      linked in the infected cell. Our results show that the yeast system is a powerful
      cellular model to study the non-sequence-specific endonucleolytic activity of IN.
      Its characterization is essential since this activity might represent a very
      important step in the retroviral infectious cycle and would provide further
      insights into the function of IN. Indeed, effectors of this activity should be
      sought as potential antiviral agents since stimulation of this enzymatic activity
      would induce the destruction of early synthesized proviral DNA.

PMID- 14644508
TI  - Disruption of the PU.1 gene in chicken B lymphoma DT40 cells and its effect on
      reported target gene expression.
AB  - Using avian B lymphoma-derived DT40 cells, we disrupted a gene encoding the
      transcription factor PU.1. The mutant mRNA codes for a protein incapable of
      functioning as a transcription factor because of the deletion of the protein's
      DNA-binding domain. The absence of a functional PU.1 protein in the mutant cells
      was confirmed by Western blotting and electrophoretic mobility shift assay,
      thereby demonstrating that PU.1 was not essential for the proliferation of DT40
      cells. An examination of the expression of several genes known to be PU.1 protein
      targets revealed almost the same levels of Ig-beta and Ig lambda L chain mRNA in
      mutant cells as in wild-type cells, indicating that the PU.1 protein plays no
      essential role in the transcription of these genes. Mutant cell doubling times
      1.3 times longer than those of wild-type cells confirmed the PU.1 protein to be
      involved in the proliferation of B lymphocytes.

PMID- 14644509
TI  - Functional analysis of the human Sprouty2 gene promoter.
AB  - Sprouty2 plays a key role in negatively modulating the fibroblast growth factor
      signaling pathway, which is required for early branching events in embryonic
      development. The expression of the murine Sprouty2 gene shows a temporally and
      spatially restricted pattern in developing lung. In order to clarify the
      molecular mechanisms governing the transcription of the Sprouty2 gene, we first
      characterized the genomic organization of the human Sprouty2 (hSpry2) gene and
      mapped its transcription start sites by 5'-rapid amplification of cDNA ends.
      Subsequently, a 4-kb sequence from the 5'-flanking region of the gene was cloned
      and determined to contain promoter activity. Detailed truncation analysis of the
      hSpry2 promoter revealed the presence of context-specific suppressor activity in
      the distal upstream region. More importantly, we demonstrated that all the
      elements necessary to achieve strong basal transcription activity were located
      within the proximal 0.4-kb region. Sequence analysis revealed that this
      functionally important proximal region contains neither TATA nor CAAT box but an
      initiator element around the transcription start site. Several cis-acting
      elements (including AP2, CREB, SP1 and Ets-1) were found to be present in the
      proximal region, and their interactions with specific nuclear proteins were
      confirmed by electrophoretic mobility shift assays. To our knowledge, this is the
      first promoter study of any mammalian Sprouty gene. We propose that the high
      level basal expression of hSpry2 is controlled by multiple transcription factors
      binding to its proximal promoter.

PMID- 14644511
TI  - Association between atherosclerosis and female lung cancer--a Danish cohort
      study.
AB  - Patients suffering from atherosclerotic diseases are prone to repeated episodes
      of ischemia/reperfusion that has been demonstrated to induce oxidative stress by
      formation of oxygen free radicals. It might therefore be expected that such
      endogenously exposure to free radicals increases the individual cancer risk in
      patients with atherosclerotic diseases. We therefore studied the sex-specific
      risk of lung cancer and other cancers in atherosclerotic patients in a
      prospective study conducted in the Copenhagen area. The study cohort was linked
      to the Danish Hospital Discharge Register and we identified 2261 1-year survivors
      of atherosclerotic diseases through 1977 and 1993, while 26150 of the study
      subjects had no record of an atherosclerotic diagnosis. After linkage to the
      Danish Cancer Registry associations between atherosclerosis and cancer were
      analysed for each sex separately by means of Cox proportional hazard regression
      models. Atherosclerotic women had a significant RR of lung cancer of 3.26 (95%
      CI: 1.95-5.46) compared to non-atherosclerotic women after adjustment for age,
      calendar period, study population, smoking habits, school education and alcohol
      consumption. No significant risk of male lung cancer, RR=1.12 (95% CI: 0.77
      1.64), or other smoking-related cancers in either sex was observed after
      multivariate adjustment. Atherosclerosis did not predict non-smoking-related
      cancers in general in either men, RR=0.91 (95% CI 0.69-1.20), or women, RR=0.93
      (95% CI: 0.64-1.35). We hypothesize that oxidative stress due to episodes of
      ischemia/reperfusion increases the risk of lung cancer in atherosclerotic females
      because of a gender specific susceptibility to oxidative DNA damage.

PMID- 14644512
TI  - Association of aryl hydrocarbon receptor and cytochrome P4501B1 expressions in
      human non-small cell lung cancers.
AB  - It has been shown that cytochrome P4501B1 (CYP1B1) is over-expressed in variety
      of tumors. The objective of this study was to examine the expression and
      localization of CYP1B1 in normal lungs and tumor tissues of non-small cell lung
      cancers (NSCLC). CYP1B1 was detectable in the microsomes of normal lungs and lung
      tumors with Western immunoblotting. Utilizing immunohistochemical staining, we
      found that CYP1B1 was constitutively expressed in the cytoplasm of smooth muscle
      cells, but not in pneumocytes. Bronchiolar epithelia from three out of 19 normal
      lungs expressed CYP1B1. Among 89 NSCLC tumor tissues, more than 50% expressed
      CYP1B1. In addition, CYP1B1 expression was more common in adenocarcinomas than in
      squamous cell carcinomas. Recently, we reported over-expression of aryl
      hydrocarbon receptors (AhR) in lung adenocarcinomas. In the present study, we
      observed an association between CYP1B1 and AhR expression in 89 NSCLC tumor
      tissues. These results suggest that CYP1B1 overexpression in NSCLC is accompanied
      by up-regulation of AhR expression.

PMID- 14644513
TI  - Suramin inhibits the growth of malignant mesothelioma in vitro, and in vivo, in
      murine flank and intraperitoneal models.
AB  - Surgical debulking of malignant mesothelioma (MM) ultimately fails due to local
      recurrence. Suramin, an inhibitor of extracellular growth factors (ECGFs), has
      demonstrated efficacy in the treatment of malignant mesothelioma in a small case
      series. Our goal was to study survival benefits and disease progression in
      several MM animal models treated with suramin as a potential agent for adjuvant
      therapy. In vitro growth of human (REN, I-45), rat (II-45) and murine (AB12)
      mesothelioma cell lines were measured with or without suramin exposure. Human and
      murine MM tumors were implanted subcutaneously into murine flanks or injected
      intraperitoneally (i.p.) into murine abdominal cavities. Dose and treatment
      schedules were optimized to reduce the rate of tumor progression and to improve
      survival curves. Suramin inhibited the in vitro growth of all cell lines,
      reaching statistical significance (P<0.01) three doubling cycles after suramin
      administration, with a maximum inhibition of 10-25% of control growth. A
      significant time- and dose-dependent effect was observed. In vivo, suramin
      inhibited the growth of MM in the xenogeneic model (55% of control growth,
      P<0.01), and in the syngeneic model at both the low and high loading doses (46
      and 36% of control growth, respectively, P<0.01). Suramin treatment inhibited in
      vivo growth in the REN intraperitoneal model shown grossly by necropsy of same
      day deaths comparing treatment and control animals. Tumor inhibition with the
      higher dose was also reflected by the lower mean tumor burden scores (control:
      4.0 and high dose: 3.4). Suramin inhibits the growth of human, murine, and rat MM
      in vitro, in a time- and dose-dependent manner. Suramin also inhibits the growth
      of human MM flank and intraperitoneal xenografts in vivo in an immunodeficient
      host, as well as the growth of syngeneic murine flank tumors in an
      immunocompetent host. These studies demonstrate that suramin may have the
      potential to provide effective therapy for MM, and that further studies are
      necessary to elucidate the survival advantage of suramin mediated MM growth
      inhibition.

PMID- 14644514
TI  - The clinical relevance of Bcl-2, Rb and p53 expression in advanced non-small cell
      lung cancer.
AB  - PURPOSE: The aim of this study was to evaluate the impact of Bcl-2,
      retinoblastoma (Rb) and p53 proteins on overall survival of 102 patients with
      locally advanced and metastatic NSCLC who underwent cisplatin-based chemotherapy.
      MATERIALS AND METHODS: Paraffin-embedded bronchial biopsy and fine-needle biopsy
      specimens were evaluated by an immunostaining method. RESULTS: Median age of
      analyzed patients was 61 years. Male/female ratio was 88/14. There were 10 (10%)
      patients with stage IIIA, 37 (36%) with stage IIIB and 55 (54%) with stage IV
      NSCLC. Only 15 (15%) tumor specimens had no detectable alterations for analyzed
      factors. Forty-six samples (45%) had positive immunostaining for p53, 61 (60%)
      had negative immunostaining for Rb and 8 (8%) had positive immunostaining for Bcl
      2. Median and 5-year survival of analyzed population was 12 months and 6%,
      respectively. In univariate analysis Bcl-2 overexpression, stage (III versus IV)
      and normal lactate dehydrogenase (LDH) serum levels were associated with better
      overall survival (P<0.02, 0.001 and 0.03). In multivariate analysis, only stage
      was identified as an independent predictive factor. CONCLUSION: High frequency of
      Rb and Bcl-2 loss was detected in patients with advanced NSCLC. P53, Rb and Bcl-2
      have not been shown to be independent predictors of survival even if Bcl-2 might
      have a particular relevance in patients with advanced NSCLC and should be better
      explored in this setting.

PMID- 14644515
TI  - The pathway study: results of a pilot feasibility study in patients suspected of
      having lung carcinoma investigated in a conventional chest clinic setting
      compared to a centralised two-stop pathway.
AB  - The best chance of cure in non-small cell lung cancer (NSCLC) is surgical
      resection, but UK rates of 8% compare poorly to 25% in the USA and Europe. Delays
      in diagnosis in the current UK system may be one reason for such discrepancy. To
      address this problem we set up a rapid diagnostic system and compared it to the
      conventional method of investigations in a pilot randomised trial. METHODS:
      Eighty-eight patients were prospectively enrolled from three District General
      Hospitals and randomised to either investigation locally or to the rapid system
      at The Royal Marsden Hospital. The pilot end-points were feasibility and audit of
      radical treatment rates to enable estimates for patient numbers for the full
      study. RESULTS: Forty-five and 43 patients were in the central and conventional
      arms, respectively (65% male, median age 69 years). There was a 4-week
      improvement in time to first treatment in those in the central arm (P=0.0025)
      with 13/30 (43%) and 9/27 (33%) patients having radical treatment in the central
      and conventional arms, respectively. Patients in the conventional arm felt the
      diagnostic process was too slow (P=0.02) while those in the central arm seemed to
      have a better care experience (P=0.01). There were significantly less visits to
      the general practitioner (GP) in the central arm (P=0.02). CONCLUSIONS: This
      pilot study demonstrates that the full study is feasible but would require the
      commitment and involvement of a large number of patients and physicians. The
      results show several advantages to investigations and diagnosis in the central
      arm, particularly in time to treatment initiation, patient satisfaction and rate
      of radical treatments. The improved rate of radical treatment could lead to an
      improved survival rate.

PMID- 14644516
TI  - Radiological examination for peripheral lung cancers and benign nodules less than
      10 mm.
AB  - To clarify the differences in radiological findings between primary lung cancers
      and benign nodules measuring less than 10mm, we examined chest computed
      tomography (CT) findings. Of 82 patients with solitary pulmonary nodules less
      than 10mm in diameter who had undergone surgical biopsy, 21 patients with primary
      lung cancer and 45 patients with benign lesions (9 patients with tuberculosis, 12
      with non-specific inflammation, 10 with benign lung tumor, 10 with intrapulmonary
      lymph nodes and 4 with others) were examined. Seven patients with atypical
      adenomatous hyperplasia and nine patients with metastatic lung cancer were
      excluded. Primary lung cancers had an ill-defined tumor margin and spiculation
      significantly more frequently than benign nodules (P<0.01). Involvement of
      bronchi or vessels was observed significantly more frequently in primary lung
      cancers than in benign nodules (P<0.05), while pleural indentation did not show
      significant differences in frequency. Retrospective chest X-ray or CT films were
      reviewed for seven patients with primary lung cancers and 12 with benign nodules,
      with a mean interval of 24+/-17 months. Primary lung cancers enlarged or appeared
      as new nodules more frequently than benign lung nodules (P<0.05). Among 17 lung
      cancer patients who underwent mediastinal lymph node dissection, the cancer was
      at a more advanced stage than T1N0M0 in four (24%). We conclude that ill-defined
      margins, spiculation, involvement of bronchi or vessels, and tumor enlargement
      visualized by CT are still important signs of malignancy even for nodules less
      than 10mm in size. Tumor size, even for lung cancers measuring less than 10mm, is
      not an indication for limited resection.

PMID- 14644517
TI  - Clinical value of video-assisted thoracoscopy for preoperative staging of non
      small cell lung cancer. A prospective study of 105 patients.
AB  - This study prospectively evaluated the usefulness of thoracoscopy for staging non
      small cell lung cancer in 105 consecutive patients. A comparison was made of TNM
      stage grouping classification according to clinical disease, thoracoscopic data,
      and pathological findings. In 40 (38%) patients, thoracoscopy was unreliable for
      assessing extent of disease due to pleural symphysis. In 13 T1 clinical lesions,
      thoracoscopy was unreliable in 5, clinical and thoracoscopic staging concurred in
      4, but 4 cases changed to T2. In 62 T2 clinical lesions, thoracoscopy was not
      feasible due to technical difficulties in 21 (34%); however, in the remaining 41
      cases, 6 lesions changed to T3 and 1 to T4. In the group of 23 T3 or T doubtful
      clinical disease, thoracoscopy was conclusive, whereas in 12 T4 clinical lesions,
      thoracoscopy contributed for tailoring treatment strategies. With regard to N
      stage, 72 N0 clinical cases, thoracoscopy revealed false negatives in 25%. N1
      clinical lesions were not evaluated due to the small number of patients. In 30 N2
      clinical lesions, thoracoscopy was incomplete in 11. In another 11 cases,
      mediastinal node involvement at nodal groups not accessible by mediastinoscopy
      was confirmed by thoracoscopy. Clinical and thoracoscopic findings were not
      concurrent in eight cases, therefore in clinical N2 lesions, the diagnostic
      accuracy of thoracoscopy was 63%. Only one case of unsuspected pleural metastasis
      was detected. Thoracoscopy-related complications occurred in nine cases. In
      summary, video-assisted thoracoscopy was useful for staging T3, T4, and T
      doubtful clinical disease as well as N2 lesions especially for the surgical
      exploration of lymph nodes at the lower paratracheal level (region 4),
      aortopulmonary window (region 5), paraaortic (region 6), posterior subcarinal
      space (region 7), paraesophageal (region 8), and inferior pulmonary ligament
      (region 9).

PMID- 14644518
TI  - The proportion of consolidation to ground-glass opacity on high resolution CT is
      a good predictor for distinguishing the population of non-invasive peripheral
      adenocarcinoma.
AB  - OBJECTIVE: If non-invasive lung carcinomas are distinguishable on computed
      tomography (CT), limited surgery can be indicated before operation as a radical
      procedure. The purpose of this study is to define high resolution CT (HRCT)
      findings that indicate pathologic T1N0M0 tumor without vessel invasion. PATIENTS
      AND METHODS: We reviewed HRCT findings and pathological specimens of 98
      consecutive patients underwent lobectomy or pneumonectomy with systematic hilar
      and mediastinal lymph node dissection from January 1996 to October 1999 for 101
      pulmonary peripheral adenocarcinomas smaller than 3cm in diameter on HRCT. A
      total of 101 consecutive surgically resected peripheral adenocarcinomas of the
      lung measuring 3.0cm or less in the maximum dimension on HRCT were examined both
      radiologically and histologically. All CT scans ware reviewed by three chest
      radiologists or pulmonologists. The following parameters were measured on HRCT:
      the greatest diameter of tumor on found on all CT cuts (Td), the greatest
      diameter of consolidation found on all CT cuts (Cdmax), and the greatest diameter
      of consolidation found on a particular CT cut (Cd). Consolidation to tumor size
      ratio at respective maximum dimensions was calculated as Cdmax/Td, and
      consolidation to tumor size ratio on the slice image with the maximum tumor
      dimension was calculated as Cd/Td. One pathologist reviewed all pathological
      specimens to determine the size of tumor, evidence of vessel invasion, etc.
      without any information of HRCT, and we compared CT findings with pathological
      findings. RESULTS: There was a statistically significant difference between
      tumors with pathologic T1N0M0 adenocarcinoma without vessel invasion (least
      invasive disease: LID) and tumors with lymph node involvement or vessel invasion
      (invasive disease: ID) in each parameter. However, only when tumors with Cdmax/Td
      smaller than 0.5 were selected as LID tumors, could ID tumors be eliminated from
      the LID group. Five-year survival rate of this population is 95.7%. CONCLUSION:
      Consolidation to tumor size ratio at respective maximum dimensions was the best
      predictor of non-invasive peripheral adenocarcinoma.

PMID- 14644519
TI  - Mediastinal restaging: EUS-FNA offers a new perspective.
AB  - STUDY OBJECTIVE: We hypothesized that transoesophageal endoscopic ultrasound
      guided fine needle aspiration (EUS-FNA) has the potential to be a valuable and
      accurate new diagnostic technique for mediastinal restaging in non-small cell
      lung cancer (NSCLC) after induction chemotherapy. The current restaging
      modalities either have a low diagnostic accuracy (computed tomography (CT) scan
      of the thorax) or they are invasive, can be technically difficult and are
      therefore not commonly performed (remediastinoscopy). METHODS AND PATIENTS:
      Nineteen consecutive patients with NSCLC and proven ipsilateral or subcarinal
      lymph node metastases (N2 disease) who had been treated with induction
      chemotherapy underwent mediastinal restaging by EUS-FNA. Patients had either a
      partial response (n=14) or stable disease (n=5) based on sequential CT scans of
      the thorax. INTERVENTIONS: EUS-FNA was performed in an ambulatory setting with
      biopsy of mediastinal lymph nodes (LN). No complications occurred. When EUS-FNA
      restaged the mediastinum as no regional lymph node metastasis (N0), surgical
      resection of the tumour with lymph node sampling or dissection was performed.
      RESULTS: The positive predictive value, negative predictive value, sensitivity,
      specificity and diagnostic accuracy of EUS-FNA in restaging mediastinal LN were
      100, 67, 75, 100 and 83%, respectively. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA
      qualifies as an accurate, safe and minimally invasive diagnostic technique for
      the restaging of mediastinal lymph nodes after induction therapy in NSCLC. In the
      future EUS-FNA might play an important role in the mediastinal restaging in
      NSCLC, particularly to identify the subgroup of down staged patients who benefit
      most from further surgical treatment.

PMID- 14644520
TI  - Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical
      resection: a radiological, histological, and immunohistochemical study.
AB  - PURPOSE: Bronchioloalveolar carcinoma (BAC) is a subtype of lung adenocarcinoma
      whose incidence is raising. Bronchioloalveolar carcinoma has a tendency to
      involve diffusely the lung. No agreement exists about whether diffuse
      bronchioloalveolar carcinoma has a multicentric or unicentric origin. The purpose
      of this work is to evaluate the correlation between intrapulmonary spread of
      bronchioloalveolar carcinoma and its histologic and immunohistochemical
      characteristics. DESIGN: Surgical specimens of 20 bronchioloalveolar carcinomas
      with radiologically proved evolution from focal to diffuse disease were retrieved
      and reviewed. Patterns of pulmonary spread were defined on the basis of CT and MR
      imaging examinations. Immunohistochemical studies were performed to investigate
      the expression of gelatinase A and alpha2-integrin. Correlation between
      immunohistochemical results and patterns of pulmonary spread was evaluated.
      Statistical evaluation was performed by using Fisher Exact Test. RESULTS: Three
      histological subtypes of bronchioloalveolar carcinoma were found: mucinous (11
      cases), non-mucinous (3 cases), and mixed adenocarcinoma with prominent
      bronchioloalveolar pattern (6 cases). Three patterns of pulmonary spread were
      depicted radiologically: parenchymal opacification (11 cases), multiple nodules
      (7 cases) and mixed pattern (2 cases). Eleven out of 12 mucin-producing versus
      none out of 8 non-mucin producing cancers developed parenchymal opacification.
      The difference was statistically significant (P<0.028). A statistically
      significant difference was also found between the development of parenchymal
      opacification and the level of alpha2-integrin: 11 out of 13 tumors with negative
      alpha2-integrin versus none out of 7 with positive alpha2-integrin
      immunoreactivity (P>0.033). CONCLUSIONS: Diffuse bronchioloalveolar carcinoma may
      develop from a prior focal cancer. Mucinous subtype is the most prone to develop
      diffuse disease with parenchymal opacification, probably representing aerogenous
      spread. Low levels of alpha2-integrin receptors were found in bronchioloalveolar
      carcinoma which developed parenchymal opacification.

PMID- 14644521
TI  - Gamma knife stereotactic radiosurgery for synchronous versus metachronous
      solitary brain metastases from non-small cell lung cancer.
AB  - A retrospective study was conducted analyzing the clinical outcome and various
      prognostic factors in patients treated with gamma knife stereotactic radiosurgery
      (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma
      (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were
      treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients
      receiving additional whole-brain radiation therapy. No one had evidence of extra
      cranial metastasis at the time of diagnosis of brain metastases. The median
      follow-up was 15.7 months for the entire population and 99.5 months for those who
      were alive at the last follow-up. Univariate and multivariate analyses were used
      to test the impact of various prognostic factors on survival. The median and 5
      year actuarial survivals for the entire cohort were 15.7 months and 10.4%,
      respectively. The presence of a metachronous versus a synchronous brain
      metastasis was the only factor significant in the univariate (P=0.045) and
      multivariate (P=0.002) analyses. Patients with metachronous solitary brain
      metastases had a significant median survival advantage compared to those with
      synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there
      was no statistically significant difference in median survival from the time of
      metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4
      months, P=0.50). The addition of WBRT did not improve overall survival (12.0
      months versus 7.7 months, P=0.73). The 5-year actuarial survival for the
      metachronous and synchronous groups were 13.2 and 8.1%, respectively. In
      conclusion, patients presenting with a solitary metachronous brain metastasis
      from NSCLC achieved longer survivals than those with a synchronous metastasis.
      The tail in the survival curves demonstrates that a prolonged survival may be
      attained in patients with solitary metastases from NSCLC. This study adds to the
      growing body of literature that supports the use of SRS in the management of this
      patient population.

PMID- 14644522
TI  - Early combined treatment with carboplatin and the MMP inhibitor, prinomastat,
      prolongs survival and reduces systemic metastasis in an aggressive orthotopic
      lung cancer model.
AB  - We studied the synthetic matrix metalloproteinase inhibitor (MMPI) prinomastat
      (AG3340) in a well-established NCI-H460 orthotopic lung cancer model that
      exhibits highly predictable regional and systemic metastatic patterns. Both
      primary and metastatic tumors express the matrix metalloproteinases (MMP-2), MT1
      MMP (MMP-14) and tissue inhibitor of metalloproteinases (TIMP-2). The anti-tumor
      activity of prinomastat was investigated both as a single agent and in
      combination therapy with carboplatin. Treatment with both carboplatin (at two
      dose levels) and prinomastat commenced when the primary lung cancer was
      approximately 200-300 mg in size and without gross or microscopic evidence of
      metastases. As single agents, prinomastat significantly reduced the incidence of
      kidney metastasis, but had no effect on metastatic frequency to other organs. As
      single agents neither drug enhanced length of survival over control animals,
      although microvessel counts in prinomastat-treated tumors were lower than in
      tumors from control animals (P<0.01). In combination prinomastat and the lower
      dose of carboplatin significantly enhanced survival over control animals, and
      over animals treated with carboplatin alone (P<0.05). Tolerance to this
      combination was assessed with body weight and serum biochemistries. At the higher
      carboplatin dose, toxicity became evident both as a single agent and in
      combination with prinomastat. Our results suggest that the administration of
      prinomastat in combination with standard cytotoxic chemotherapy during early
      stages of tumor growth and metastasis may prolong survival in non-small cell lung
      cancer (NSCLC) patients.

PMID- 14644523
TI  - Gemcitabine and low dose carboplatin in the treatment of elderly patients with
      advanced non-small cell lung cancer.
AB  - BACKGROUND: Fifty percent of lung cancers arise in patients over 65 years old and
      30% in those over 70. The aim of this study was to evaluate response, survival
      and tolerability of the combination carboplatin-gemcitabine in elderly patients
      with advanced non-small cell lung cancer (NSCLC). METHODS: Between May 1998 and
      December 2000, 88 patients were included. Median age was 74 (range 65-83).
      Treatment consisted of gemcitabine 1250 mg/m(2) (1000 mg/m(2) in the first six
      patients) on days 1 and 8, and carboplatin AUC=4 on day 1, every 21 days.
      Prognostic factors for survival were analysed. Performance status (PS) and
      symptoms were evaluated before and after three and six courses. RESULTS: A total
      of 400 cycles were administered (median of four per patient). WHO grades 3-4
      toxicities were: neutropenia in 13% of the cycles, thrombocytopenia and anaemia
      in 4.5 and 14.7% of patients in any cycle. There was one treatment-related death.
      According to the intent-to-treat analysis, 33 patients achieved objective
      response, 33 had stable disease, and 22 had treatment failure (progression in 18
      patients). Median and 1 year survival were 9 months and 34%, respectively. Median
      time to progression was 8 months. Only disease stage and PS showed independent
      prognostic value. Comorbidity and PS displayed no close correlation. Symptom
      improvement was seen as follows: pain (61.7%), dyspnea (50%), haemoptysis (80%),
      anorexia (62.5%) and asthenia (61.5%). CONCLUSIONS: The combination carboplatin
      gemcitabine at these doses is feasible in elderly patients with advanced non
      small cell lung cancer. Tolerability and toxicity are acceptable. Response rate
      and survival stand in the range of the most active regimens. Comorbidity and PS
      showed prognostic independence.

PMID- 14644524
TI  - Phase II study of gemcitabine-cisplatin-paclitaxel triplet as induction
      chemotherapy in inoperable, locally-advanced non-small cell lung cancer.
AB  - PURPOSE: Our objective was to determine the activity in terms of response rate,
      surgical resectability, and the tolerability of the new three-drug combination
      gemcitabine-cisplatin-paclitaxel (GCP) in unresectable stage IIIA(N2) and IIIB
      non-small cell lung cancer (NSCLC). PATIENT AND METHODS: Forty-two chemo-naive
      patients with stage IIIA(N2)-IIIB NSCLC, median age of 59 years, Eastern
      Cooperative Oncology Group (ECOG) performance status of 0 or 1, and the ability
      to tolerate pneumectomy, received gemcitabine (Gem) 1000 mg/m(2) IV days 1 and 8,
      cisplatin (CDDP) 50 mg/m(2) IV days 1 and 8, paclitaxel 125 mg/m(2) 1h infusion
      IV days 1 and 8, every 21 days for 3 cycles. After induction chemotherapy,
      patients were evaluated for surgery or definitive radiotherapy. RESULTS: Grade 3
      4 neutropenia was the main hematologic toxicity, occurring in 28% of patients.
      Grade 3-4 thrombocytopenia was observed in only 11% of cases. No neutropenic
      fever or bleeding episodes were recorded. Severe non-hematologic toxicity was
      uncommon. Thirty (71%, 95% CI: 57.2-84.7%) of the 42 eligible patients had
      objective responses (1 complete and 29 partial responses). After induction
      chemotherapy, 21 patients (50%) went to surgery. Complete resection was obtained
      in 16 patients (38%). Viable tumor was present in 18 of 21 resection specimens.
      In three cases only necrotic tumor cells were identified, for a pathological
      complete response of 7%. With a median follow-up of 13.9 months, median time to
      progression was 17.4 months, median survival 21.7 months and estimated 1-year
      survival 92%. CONCLUSIONS: GCP combination is active and well tolerated in
      locally-advanced, non-resectable NSCLC. The activity profile, in terms of
      response and surgical resection rate, is comparable to that obtained with
      standard doublets.

PMID- 14644525
TI  - Remediastinoscopy: comments and updated results.

PMID- 14644527
TI  - Evolution and prognostic accuracy of staging system for NSCLC.

PMID- 14644528
TI  - CT and MRI for staging of locally advanced non-small cell lung cancer.

PMID- 14644529
TI  - The use of positron emission tomography in initial staging and follow-up
      evaluation in NSCLC.

PMID- 14644530
TI  - Surgery in locally advanced non-small cell lung cancer.

PMID- 14644531
TI  - Superior sulcus tumors and Pancoast's syndrome.

PMID- 14644532
TI  - Surgical outcomes of N2 and T3-4 non-small cell lung cancer.

PMID- 14644533
TI  - Adjuvant therapy for locally advanced non-small cell lung cancer.

PMID- 14644534
TI  - Combined modality therapy for non-small cell lung cancer, past, present, and
      future.

PMID- 14644535
TI  - Prophylactic cranial irradiation in high-risk non-small cell lung cancer
      patients.

PMID- 14644536
TI  - Combined modality therapy for unresectable non-small cell lung cancer.

PMID- 14644537
TI  - Induction therapy for stage III lung cancer.

PMID- 14644548
TI  - Molecular comparison of apocrine released and cytoplasmic resident carbonic
      anhydrase II.
AB  - We have previously shown that carbonic anhydrase II usually described as a
      cytoplasmic resident isoform (cCAH II) is secreted by the rat coagulating gland
      (sCAH II) via the apocrine secretion mode. To get more detailed information why
      CAH II is cytoplasmic resident in some organs and secreted in others we cloned
      and sequenced the cDNA of rat coagulating gland sCAH II. The sequence of the
      secretory form was found to be completely identical with the cCAH II. Therefore,
      a signal peptide targeting sCAH II for apocrine secretion can be excluded.
      Considering the fact that other apocrine secreted proteins are glycosylated, cCAH
      II and sCAH II were analyzed for carbohydrate substitutions. As expected for a
      cytoplasmic protein, no glycan modification could be identified in cCAH II. In
      contrast, sCAH II carried exclusively Gal, GlcNAc and Fuc residues in a molar
      ratio of 1:0.8:0.5. Carbohydrate linkage analyses demonstrated the presence of
      terminal Fuc, terminal, 3-substituted and 3,6-disubstituted Gal as well as 4
      substituted and 3,4-disubstituted GlcNAc. The composition of the glycan
      constituents as well as deglycosylation experiments clearly proved that sCAH II
      carries neither conventional mammalian-type N-glycans nor mucin-type O-linked
      sugar chains. Lacking a signal peptide for ER translocation, glycosylation of
      sCAH II must occur within the cytoplasmic compartment. Further studies have to
      elucidate whether or not glycosylation of sCAH II is essential for the apocrine
      release of the protein.

PMID- 14644549
TI  - Ozone-induced inactivation of antioxidant enzymes.
AB  - Ozone is an air pollutant that damages a variety of biomolecules. We investigated
      ozone-induced inactivation of three major antioxidant enzymes. Cu/Zn superoxide
      dismutase was inactivated by ozone in a concentration-dependent manner. The
      concentration of ozone for 50% inactivation was approximately 45 microM when 10
      microM Cu/Zn superoxide dismutase was incubated for 30 min in the presence of
      ozone. SDS-polyacrylamide gel electrophoresis (PAGE) showed that the enzyme was
      randomly fragmented. Both ascorbate and glutathione were very effective in
      protecting Cu/Zn superoxide dismutase from ozone-induced inactivation. The other
      two enzymes, catalase and glutathione peroxidase, were much more resistant to
      ozone than Cu/Zn superoxide dismutase. The ozone concentrations for 50%
      inactivation of 10 microM catalase and glutathione peroxidase were 500 and 240
      microM, respectively. SDS-PAGE demonstrated that ozone caused formation of high
      molecular weight aggregates in catalase and dimerization in glutathione
      peroxidase. Glutathione protected catalase and glutathione peroxidase from ozone
      but the effective concentrations were much higher than that for Cu/Zn superoxide
      dismutase. Ascorbate was almost ineffective. The result suggests that, among the
      three antioxidant enzymes, Cu/Zn superoxide dismutase is a major target for ozone
      induced inactivation and both glutathione and ascorbate are very effective in
      protecting the enzyme from ozone.

PMID- 14644550
TI  - Rat kidney acylase I: further characterisation and mutation studies on the
      involvement of Glu 147 in the catalytic process.
AB  - Rat kidney acylase I was characterised by performing site-directed mutagenesis
      and enzymatic analysis in the presence of various chemical inhibitors. Site
      directed mutagenesis on E147 and overexpression of the protein in a bacterial
      system, revealed the importance of this residue in enzymatic activity, it
      corresponds to the putative catalytic E175 in carboxypeptidase G2 from
      Pseudomonas aeruginosa. The reactivity of histidine and cysteine residues of
      acylase I with diethylpyrocarbonate (DEPC) and mercuric chloride, respectively,
      showed that these two amino acids are required for the enzyme to be fully active.
      Interestingly, the effects of mercuric chloride on rat kidney acylase I were not
      as great as those on the porcine enzyme, in agreement with previously observed
      differences between the two enzymes. Moreover, N-[3-(2-furyl)-acryloyl-L
      methionine] (FA-Met) a synthetic substrate of the porcine acylase I was found to
      be an inhibitor of the rat kidney enzyme. These results strongly suggest the
      existence of differences between the active site of rat and porcine kidney
      acylases I. Lastly, the rat kidney enzyme was as sensitive as its porcine
      counterpart to two metal chelating agents, 1,10-phenanthroline and
      ethylenediamine tetraacetate (EDTA).

PMID- 14644551
TI  - Morphological and biochemical modifications induced by a static magnetic field on
      Fusarium culmorum.
AB  - The effects of the exposure to a static magnetic field (sMF) of 0.3 +/- 0.03 T on
      the Fusarium culmorum were investigated in vitro. sMF inhibition of mycelia
      growth was accompanied by morphological and biochemical changes. Fungal conidia
      germination and cell viability were also reduced. We provide evidence of the
      influence of sMF on Ca(2+)-dependent signal transduction pathways involved in
      conidia germination. Perturbation of these pathways by adding different compounds
      (i.e. CaCl(2), phorbol 12-myristate 13-acetate, neomycin, EGTA, LiCl) to the
      medium, suggested that exposed conidia are unable to mobilise calcium from
      intracellular stores and that the hindered mechanism may be IP(3)-dependent.

PMID- 14644552
TI  - Isoproterenol increases active lipoprotein lipase in adipocyte medium and in rat
      plasma.
AB  - White adipose tissue (WAT) lipoprotein lipase (LPL) activity channels diet fat
      towards storage in adipocytes. Adrenaline (ADR) is accepted to reduce WAT or
      adipocyte LPL activity (LPLa), but available data are not clear-cut regarding
      long exposure to ADR in vitro or in vivo. We studied the effects of long
      exposures to ADR or beta-adrenergic agonist on LPL: in isolated rat adipocytes (3
      h) and in rats (>1 day). Isoproterenol (ISO) (1 microM) did not alter LPLmRNA nor
      LPLa in adipocytes, but increased LPLa in medium more than twofold (3.58 +/- 0.35
      vs. 1.32 +/- 0.35 mU/10(6) adipocytes, P < 0.001). Effect was time (not present
      at 1 h, clear at 2 h) and concentration dependent (high sensitivity from 10 to
      100 nM, max at 1 microM). Adenylate cyclase activator or cyclic AMP (cAMP)
      analogue produced a similar increase. Thus in adipocytes ISO produced an increase
      in LPLa release and/or a decrease in extracellular LPLa degradation. ADR or ISO
      treated rats had a two to fourfold decrease in WAT LPLa vs. unchanged LPLmRNA.
      This decrease was 10-fold in WAT heparin-releasable LPLa (5.7 +/- 0.6 vs. 57.3 +/
      10.2 mU/g, P < 0.001), which represents peri/extracellular LPLa. Plasma LPLa was
      increased 11-fold by ADR (3.30 +/- 0.58 vs. 0.32 +/- 0.08 mU/ml, P < 0.001)
      whereas only threefold by ISO (P > 0.01). We suggest that in vivo ADR increased
      release of active LPL to plasma from endothelial cells of LPL-rich tissue(s)-WAT
      was probably one of these tissues releasing LPL since it lost 90% of its
      peri/extracellular LPLa-and/or decreased degradation of plasma active LPL. Since
      liver LPLa was not increased, plasma active LPL might be kept away from hepatic
      degradation by binding to stabilising entities in plasma (fatty acids (FA),
      lipoproteins or soluble heparan sulphates (HS)). In conclusion, we believe this
      is the first report stating that: (a) ISO increases LPLa in isolated adipocyte
      medium, and (b) ADR administration to rats decreases WAT extracellular active LPL
      and increases preheparin plasma active LPL.

PMID- 14644553
TI  - Isolation, characterization and biological activity of acidic phospholipase A2
      isoforms from Bothrops jararacussu snake venom.
AB  - Acidic phospholipase A(2) (PLA(2)) isoforms in snake venoms, particularly those
      from Bothrops jararacussu, have not been characterized. This article reports the
      isolation and partial biochemical, functional and structural characterization of
      four acidic PLA(2)s (designated SIIISPIIA, SIIISPIIB, SIIISPIIIA and SIIISPIIIB)
      from this venom. The single chain purified proteins contained 122 amino acid
      residues and seven disulfide bonds with approximate molecular masses of 15 kDa
      and isoelectric points of 5.3. The respective N-terminal sequences were:
      SIIISPIIA-SLWQFGKMIDYVMGEEGAKS; SIIISPIIB-SLWQFGKMIFYTGKNEPVLS; SIIISPIIIA
      SLWQFGKMILYVMGGEGVKQ and SIIISPIIIB-SLWQFGKMIFYEMTGEGVL. Crystals of the acidic
      protein SIIISPIIB diffracted beyond 1.8 A resolution. These crystals are
      monoclinic with unit cell dimensions of a = 40.1 A, b = 54.2 A and c = 90.7 A.
      The crystal structure has been refined to a crystallographic residual of 16.1%
      (R(free) = 22.9%). Specific catalytic activity (U/mg) of the isolated acidic
      PLA(2)s were SIIISPIIA = 290.3 U/mg; SIIISPIIB = 279.0 U/mg; SIIISPIIIA = 270.7
      U/mg and SIIISPIIIB = 96.5 U/mg. Although their myotoxic activity was low,
      SIIISPIIA, SIIISPIIB and SIIISPIIIA showed significant anticoagulant activity.
      However, there was no indirect hemolytic activity. SIIISPIIIB revealed no
      anticoagulant, but presented indirect hemolytic activity. With the exception of
      SIIISPIIB, which inhibited platelet aggregation, all the others were capable of
      inducing time-independent edema. Chemical modification with 4-bromophenacyl
      bromide did not inhibit the induction of edema, but did suppress other
      activities.

PMID- 14644554
TI  - Purification and characterization of the Streptococcus salivarius methionine
      aminopeptidase (MetAP).
AB  - Streptococcus salivarius methionine aminopeptidase (MetAP) was purified from a
      recombinant Escherichia coli strain containing the S. salivarius map gene, which
      codes for MetAP. S. salivarius map coded for a protein of 286 amino acids with a
      calculated molecular mass of 31,723 Da and a pI of 4.6. The native enzyme eluted
      from a Superdex column as a protein with a molecular mass of 30.6 kDa and cleaved
      N-terminal Met of peptide only when the penultimate amino acid was Gly, Ala, Ser,
      Val, Pro, or Thr. The enzyme was more active against tetrapeptides than
      tripeptides and did not recognize dipeptides. It required the presence of a metal
      cation for activity, with a preference for Co(2+) over Mn(2+). S. salivarius
      MetAP has a pH optimum of 8.0 and an optimal temperature at 50 degrees C. The S.
      salivarius protein had an extra sequence of 24 amino acids between two conserved
      aspartate residues involved in the coordination of the metal ion. A similar extra
      sequence is present in MetAP from other streptococci and from Lactococcus lactis,
      but not from other bacteria or eukaryotes.

PMID- 14644555
TI  - Consequences of a six residual deletion from the N-terminal of rabbit muscle
      creatine kinase.
AB  - A mutant of dimeric rabbit muscle creatine kinase (CK), in which six residues
      (residues 2-7) at the N-terminal were removed by the PCR method, was studied to
      assess the role of these residues in dimer cohesion and to determine the
      structural stability of the protein. The specific activity of the mutant was
      70.39% of that of the wild-type CK, and the affinity for Mg-ATP and CK substrates
      was slightly reduced compared with the wild-type protein. The structural
      stability of the mutant was investigated by a comparative equilibrium urea
      denaturation study and a thermal denaturation study. The data acquired by
      intrinsic fluorescence and far-UV circular dichroism (CD) during urea unfolding
      indicated that, the secondary and tertiary structures of the mutant were more
      stable than those of wild-type CK. Furthermore, results of 8-anilino-1
      naphthalene-sulfonic acid (ANS) fluorescence demonstrated that the hydrophobic
      surface of the mutant CKND(6) was more stable during urea titration. Data from
      size exclusion chromatography (SEC) experiments indicated that deletion of the
      six N-terminal residues resulted in a relatively loose molecular structure, but
      the dissociation of the mutant CKND(6) occurred later during the unfolding
      process than for wild-type CK. Consistent with this result, the differential
      scanning calorimetry (DSC) profiles demonstrated that the thermal stability of
      the enzyme was increased by removal of the six N-terminal residues. We conclude
      that a more stable quaternary structure was obtained by deletion of the six
      residues from the N-terminal of wild-type CK.

PMID- 14644556
TI  - 1H NMR studies of the effect of mutation at Valine45 on heme microenvironment of
      cytochrome b5.
AB  - 1D and 2D (1)H NMR were employed to probe the effects on the heme
      microenvironment of cytochrome b(5) caused by the mutation from Val45 to Tyr45,
      His45 and Glu45. Compared with wild type (WT) cytochrome b(5), in all mutants the
      heme ring are CCW rotated relative to the imidazole planes of axial ligands and
      the angles beta between two axial ligand imidazole planes are not changed, being
      in agreement with the temperature dependence of the shifts of the heme protons.
      The ratios of heme isomers (major to minor) are smaller than that in WT. The 4
      vinyl group of the heme in V45Y assumes cis-orientation, being similar to that of
      WT, while in V45E and V45H, both cis and trans orientation are found. The
      relationships between the structure and biological function of the mutants are
      discussed in terms of the geometry of heme and axial ligands, the hydrophobicity
      of heme pocket and the electrostatic potential of the heme-exposed area.

PMID- 14644557
TI  - Inhibition of enzymatic and pharmacological activities of some snake venoms and
      toxins by Mandevilla velutina (Apocynaceae) aqueous extract.
AB  - Phospholipases A(2) (PLA(2)) are multifunctional proteins which exhibit varied
      biological activities correlated to the structural diversities of the sub
      classes. The crude aqueous extract from subterranean system of Mandevilla
      velutina, a plant found in Brazilian savanna, was assayed for its ability to
      inhibit biological activities of several snake venoms and isolated PLA(2)s. The
      extract induced total inhibition of the phospholipase activity of Crotalus
      durissus terrificus venom and only partial inhibition of Bothrops venoms. When
      assayed against purified toxins, the highest efficacy was detected against CB and
      crotoxin, while almost ineffective against PLA(2)s from the genus Bothrops.
      Although M. velutina crude extract significantly inhibited the myotoxic activity
      of C. d. terrificus venom and CB, it produced only partial inhibition of either
      Bothrops jararacussu venom or its main myotoxins BthTX-I (basic Lys49), BthTX-II
      (basic Asp49) and BthA-I-PLA(2) (acidic Asp49). The extract exhibited also full
      inhibition of hemorrhage caused by Bothrops alternatus, Bothrops moojeni and
      Bothrops pirajai snake venoms, but partial inhibition (90%) of that induced by B.
      jararacussu venom. The extract was ineffective to inhibit the fibrinogenolytic
      activity of B. moojeni, B. alternatus and B. pirajai crude venoms, while their
      caseinolytic activity was only partially inhibited. No inhibition of the
      anticoagulant activity, although partial reduction of the edema-inducing activity
      of C. d. terrificus and B. alternatus crude venoms, CB, PrTX-I, BthTX-I and
      crotoxin was observed. Besides extending survival of mice injected with lethal
      doses of C. d. terrificus and B. jararacussu venoms, M. velutina extract
      decreased to 50% the lethality of mice. Extracts of 18 month old micropropagated
      plants were able to partially neutralize the effect of the crude venoms and
      toxins.

PMID- 14644558
TI  - Elevated levels of serum alpha(2) macroglobulin in wild black bears during
      hibernation.
AB  - Bear serum alpha(2) macroglobulin (alpha(2)M) was purified by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and partially characterized
      by tryptic digestion of alpha(2)M and analysis of the peptides by peptide mass
      fingerprinting. The molecular weight of bear serum alpha(2)M was 181 kDa, same as
      for human serum alpha(2)M, on SDS-PAGE. However, the MALDI mass spectrum of the
      tryptic digested bear serum alpha(2)M showed that it is different from human
      alpha(2)M or other data bank proteins. Liquid chromatography (LC)/mass
      spectrometry (MS)/MS of the proteolytic products of bear serum alpha(2)M showed
      eight peptides that had similarities to human alpha(2)M suggesting that the
      protein of interest was indeed alpha(2)M of bear. The polyclonal antibody against
      bear serum alpha(2)M recognized only one protein from the western blot of bear
      serum proteins. It also recognized human alpha(2)M. The levels of serum alpha(2)M
      were significantly increased during hibernating state as compared to active state
      of bears indicating its protective role from the consequences of the metabolic
      depression during hibernation.

PMID- 14644559
TI  - cDNA cloning, identification and characterization of a novel cystatin from the
      tentacle of Cyanea capillata.
AB  - Cystatin is of interest from biochemical and evolutionary prospective, and also
      has been applied in biotechnology. In this paper, a novel cystatin was found by
      EST sequence analysis of the cDNA library of Cyanea capillata tentacle. The
      sequence of a full-length cDNA clone contained an open reading frame encoding a
      putative 18-residue signal peptide and a mature protein of 113 amino acids, which
      showed only 26% identities to Family 2 cystatins and had its own characteristic
      enzyme-binding motifs, Ser(97)-Trp(98), which had not been found in any other
      known cystatins. Thus, the novel cystatin cloned from jellyfish was designated as
      cystatin J, which may belong to a new family of cystatin, called Family 4. The
      mature cystatin J was produced in Escherichia coli as a thioredoxin (Trx) fusion
      protein using the pET expression system and purified by affinity and cation
      exchange chromatography. The recombinant cystatin J of approximately M(r) =
      12,800 displayed an obvious inhibition of papain (K(i) value below 0.5 nM), in
      competition with substrate. Thus, the recombinant cystatin J was a functional
      cystatin in spite of relatively lower sequence similarity with other cystatins.
      Activity of the novel cystatin was stable at pH 4-11 at 4 degrees C, but unstable
      at neutral pH at >50 degrees C.

PMID- 14644560
TI  - Interaction of isomeric forms of xanthophyll pigment zeaxanthin with
      dipalmitoylphosphatidylcholine studied in monomolecular layers.
AB  - Two-component monomolecular layers were formed with DPPC and two stereoisomers of
      zeaxanthin 9-cis and 13-cis at the argon-water interface. Very distinct over
      additivity which represents affection of a lipid arrangement in the membrane has
      been observed in the case of zeaxanthin 9-cis (maximum at 20 mol%) but not in the
      case of zeaxanthin 13-cis. The differences in the organization of the isomers of
      zeaxanthin-DPPC monolayers are interpreted in terms of the different orientation
      of both xanthophylls at the interface observed at relatively high surface
      pressures (>25 mN/m) comparable to the surface pressures of biomembranes. The
      results are consistent with the model according to which zeaxanthin 9-cis adopts
      a vertical orientation at the polar-nonpolar interface in contrast to zeaxanthin
      13-cis, which is oriented horizontally owing to the fact that it interacts by two
      hydroxyl groups with the same hydrophobic-hydrophilic interface in the monolayer.
      The findings are discussed in comparison with the behavior of zeaxanthin in the
      conformation all-trans in the same system. Zeaxanthin all-trans forms efficiently
      molecular aggregates in the mixed monolayers in contrast to cis isomers. Circular
      dichroism measurements show the formation of molecular structures by zeaxanthin
      13-cis that are interpreted as dimers. FTIR measurements show that these dimers
      are stabilized by van der Waals interactions unlike aggregated structures formed
      by all-trans zeaxanthin that are stabilized by hydrogen bonding. Physiological
      importance of the differences in aggregation and orientation of stereoisomers of
      zeaxanthin in lipid environment is discussed.

PMID- 14644561
TI  - Effect of macromolecules and Triton X-100 on the triplet of aggregated
      chlorophyll in aqueous solution.
AB  - Chlorophyll a (Chla) in aqueous solution (2-6% acetone) is present as mono- and
      dihydrated aggregated forms which are characterized by specific ground state
      absorption spectra. The amount of dihydrated form is larger in the presence of
      macromolecules, such as bovine serum albumin (BSA), lysozime and polyvinyl
      alcohol (PVA), increasing from BSA to lysozime and PVA. Chla in aqueous acetone
      with and without macromolecules is characterized by low fluorescence and the
      absence of triplet-triplet (T-T) absorption. The ratio of dihydrated to
      monohydrated forms is significantly influenced by triton X-100. For lower triton
      X-100 concentrations, i.e. smaller than the critical micelle concentration of
      0.26 mM (cmc), dihydrated forms are converted into monohydrated in both aqueous
      acetone and the presence of BSA or lysozime. In the presence of PVA dihydrated
      forms appeared to be resistant to triton X-100 action. Moreover, for triton X-100
      concentrations of 2-3 times higher than cmc the amount of these forms is
      increased with time. T-T absorption of both mono- and dihydrated Chla aggregates
      was not detected in the presence of [triton X-100] < cmc. The lack of T-T
      absorption in aqueous acetone solution as well as in the presence of
      macromolecules implies that the triplet lifetime of the chlorophyll aggregates is
      short (tauT<10 ns) and/or the quantum yield of intersystem crossing is small (<5
      x 10(-3)). The Chla monomers start to be formed as solubilized in the micelle for
      [triton X-100] larger than cmc, showing substantial fluorescence and T-T
      absorption.

PMID- 14644562
TI  - Solution conformation of a nitrobenzoxadiazole derivative of the polyene
      antibiotic nystatin: a FRET study.
AB  - Nystatin is a polyene antibiotic frequently applied in the treatment of topical
      fungal infections. In this work, a 7-nitrobenz-2-oxa-1,3-diazole (NBD) hexanoyl
      amide derivative of nystatin was synthesized and its detailed photophysical
      characterization is presented. The average conformation of the labelled
      antibiotic in tetrahydrofuran, ethanol and methanol was determined by
      intramolecular (tetraene to NBD) fluorescence resonance energy transfer
      measurements. At variance with the literature [Can. J. Chem. 63 (1985) 77-85], it
      was concluded that there is no need to invoke a solvent-dependent conformational
      equilibrium between extended and closed conformers of the antibiotic, because the
      mean tetraene-to-NBD separating distance was found to remain constant
      (approximately 18 A) in all the solvents studied. In addition, the large solvent
      dependence of the fluorescence anisotropy observed for the non-derivatized
      nystatin, was rationalized on the basis of the prolate ellipsoidal geometry of
      the molecule. It was concluded that the rod shaped and amphipathic antibiotic
      remains monomeric in different solvents within the concentration range studied (2
      20 microM).

PMID- 14644563
TI  - Photodynamic effect of hypericin and a water-soluble derivative on isolated
      crayfish neuron and surrounding glial cells.
AB  - Hypericin (Hyp) has been proposed as a fluorochrome for fluorescence diagnostics
      and as a photosensitizer for photodynamic therapy of cancer. However, its
      insolubility in water is a serious drawback. A novel water-soluble hypericin
      derivative (Hyp-S) has been constructed, using polyvinylpyrrolidone as a carrier.
      We used the crayfish stretch receptor, consisting of receptor neuron and
      satellite glial cells, for comparison of the photodynamic effects of Hyp and Hyp
      S. Hyp-S was more toxic in the dark than Hyp and inactivated the neurons at
      concentrations exceeding 4 microM while Hyp was toxic to the neurons only at the
      concentrations larger than 20 microM. Electrophysiological investigations
      revealed polyphasic neuron responses to photosensitization with Hyp as well as
      with Hyp-S (1 microM concentration, 30 min incubation; irradiation with filtered
      light from a lamp with an emission maximum near 600 nm and an intensity of 0.2
      W/cm2). In the concentration range 1-4 microM Hyp-S was more phototoxic than Hyp.
      Fluorescence microscopy showed that both sensitizers were predominately localized
      in the glial envelope surrounding the neuron. A minor fraction of hypericin was
      found in the neuron perinuclear area rich in cytoplasm organelles. This suggests
      the potential application of Hyp and Hyp-S for visualization and selective
      photodynamic treatment of malignant gliomas.

PMID- 14644564
TI  - Photobiological characteristics and photosynthetic UV responses in two Ulva
      species (Chlorophyta) from southern Spain.
AB  - The effect of different wavebands of artificial UV (UVB and UVA) and
      photosynthetically active radiation (PAR) was assessed in two species of the
      genus Ulva, U. olivascens and U. rotundata, from southern Spain in order to test
      for possible differences in acclimation of photosynthesis. Both species share
      similar morphology but are subject to different light environments: U. rotundata
      is an estuarine alga, inhabiting subtidal locations, while U. olivascens is an
      intertidal, sun-adapted organism. Algae were exposed to three different UV
      conditions, PAR+UVA+UVB, PAR+UVA and PAR for 7 d. Short-term exposure (6 h) was
      also carried out, using two PAR levels, 150 and 700 micromolm(-2)s(-1). Pigment
      contents and photosynthesis vs. irradiance curves from oxygen evolution were used
      to contrast sun- and shade adaptation between these species. O2-based net
      photosynthesis (Pmax) and PAM-chlorophyll fluorescence (optimal quantum yield,
      Fv/Fm) were used as parameters to evaluate photoinhibition of photosynthesis in
      the experiments. The results underline different photobiological characteristics
      among species: the subtidal U. rotundata had higher contents of pigments (Chl a,
      Chl b and carotenoids) than the sun-adapted U. olivascens, which resulted in
      higher thallus absorptance and P-I parameters characterized by higher
      photosynthetic efficiency at limiting irradiances (alpha) and lower saturating
      points for photosynthesis (Ek). After 7 d exposure, photoinhibition of Fv/Fm was
      close to 40-45% in both species. Differences between UV treatments were seen in
      U. rotundata after 5 d and after 7 d in U. olivascens, in which PAR+UVA impaired
      strongly photosynthesis (80%). Such patterns were correlated with a progressive
      decrease in pigment contents, specially chlorophylls. In short-term (6 h)
      exposures, combinations of UVA+UVB and high PAR level resulted in high rates of
      photoinhibition of chlorophyll fluorescence (68-92%) in U. rotundata, whereas in
      U. olivascens photoinhibition ranged between 42% and 53%. Photoinhibition under
      low PAR combined to UV radiation was lower than observed under high PAR. Net O2
      Pmax revealed similar response among the species, with maximal photoinhibition
      rates close to 60% in algae incubated under high PAR+UVA+UVB. In the case of UV
      exposure in combination with low PAR, the highest photoinhibition rates were
      measured in U. rotundata.

PMID- 14644565
TI  - Allophycocyanin complexes from the phycobilisome of a thermophilic blue-green
      alga Myxosarcina concinna Printz.
AB  - The core polypeptide components of the intact phycobilisomes (PBSs) prepared by
      the sucrose gradients in 0.9 M phosphate buffer from a thermophilic
      cyanobacterium Myxosarcina concinna Printz were investigated. Three
      allophycocyanins, designated AP1, AP2, and AP3, of the PBS cores were
      successfully prepared by using the gradient polyacrylamide gel electrophoresis
      (PAGE) performed in neutral, instead of alkaline, buffer system. The spectral
      properties of AP2 and AP3 demonstrated that they both had fluorescence emission
      maxima at 684/685 nm at 77 K, which was identical to those of the intact PBSs,
      and showed the absorption of allophycocyanin B (AP-B) subunit. Sodium dodecyl
      sulfate-PAGE revealed that the three biliprotein complexes were all composed of
      heterogeneous subunits and two more linker polypeptides (Ls), AP1
      alpha(22.3)alpha(19.5)beta(17.4)beta(15.7)L(13.8)L(11.3)L(9.5), AP2
      alpha(22.3)alpha(19.5)beta(17.4)beta(15.7)beta(15.1)L(11.3)L(9.5), and AP3
      alpha(22.3)alpha(19.5)beta(17.4)beta(15.7)beta(15.1)L(11.3)L(9.5)L(8.3). Compared
      with the characteristics of AP1, beta(15.1), which belonged to the beta subunit
      group, was the AP-B subunit of AP2 and AP3. Because AP2 was only obtained
      together with the PBS by the aid of 2% (v/v) Triton X-100, but not AP3, it was
      closely related to anchoring the PBS core on thylakoid membranes though the
      polypeptide analysis showed that AP2 had no core-membrane linker (LCM).
      Aggregates of the three AP biliproteins were proposed based on the present
      results, and their functions in the PBS core construction and the energy transfer
      to PS II and PS I were discussed.

PMID- 14644566
TI  - N-acetyl-L-cysteine prevents DNA damage induced by UVA, UVB and visible radiation
      in human fibroblasts.
AB  - The thiol N-acetyl-L-cysteine (NAC) is a source of cysteine for the synthesis of
      the endogenous antioxidant glutathione (GSH) which is depleted by ultraviolet
      radiation. It is also associated with the scavenging of reactive oxygen species
      (ROS). In this study the effects of NAC were examined in cultured human
      fibroblasts during prolonged exposure to ultraviolet B (UVB), ultraviolet A (UVA)
      and visible irradiation (280-700 nm), delivered by a 150 W xenon-arc lamp. The
      alkaline comet assay was used to assess the DNA damage in individual cells. It
      was found that incubating skin and lung fibroblasts at 37 degrees C for 1 h with
      an optimal 6 mM NAC supplement prior to light exposure, significantly reduced the
      level of DNA damage in both cell types, however, the skin fibroblasts were less
      sensitive to xenon-arc lamp irradiation than lung fibroblasts. NAC incubation
      resulted in an initial delay in DNA damage when the cells were irradiated. There
      was also a significant reduction in the overall levels of DNA damage observed
      with continued irradiation. NAC significantly reduced the DNA damage produced in
      lung fibroblasts depleted of normal GSH protection by the glutamylcysteinyl
      synthetase inhibitor, L-buthionine-[S,R]-sulfoximine. Although the specific
      mechanism of NAC protection has not yet been elucidated, these results support
      the hypothesis that NAC may protect the cells directly, by scavenging ROS induced
      by UVA and visible radiation, and indirectly by donating cysteine for GSH
      synthesis.

PMID- 14644567
TI  - Synthesis, characterization and photodynamic activity of phenmethylamino
      demethoxy-hypocrellin B.
AB  - Two phenmethylamino hypocrellin B derivatives are novel photodynamic agents
      synthesized by a mild reaction between hypocrellin B and phenmethylamine. The red
      absorption of the photosensitizers is enlarged distinctly and the peri
      hydroxylated perylenequinone structure of the parent HB is preserved. 9,10
      diphenyl-anthracene (DPA) bleaching and electron paramagnetic resonance (EPR)
      spin trapping techniques were used to study the photodynamic activities of the
      phenmethylamino hypocrellin B derivatives in the presence of oxygen. Singlet
      oxygen (1O2) and superoxide anion radical (O2*-) generated in the process of
      illumination of the phenmethylamino hypocrellin B in aerobic solution were
      observed. The photodamage of PMAHBs to MGC803 cancer cells was investigated in
      vitro. The results in vitro reveal that the phenmethylamino hypocrellin B
      derivatives show a much less significant decrease in cytotoxicity than that of
      their parent HB. It exhibits higher selectivity of light-orientation, which can
      decrease the damage to normal tissues by irradiating the tumor tissues, and so
      increases the drug safety.

PMID- 14644568
TI  - Antitumor activity of 4-amino and 8-methyl-4-(3diethylamino
      propylamino)pyrimido[4',5':4,5]thieno (2,3-b) quinolines.
AB  - The interaction of 4-aminopyrimido [4',5':4,5] thieno (2,3-b) quinoline and 8
      methyl-4-(3-diethylaminopropylamino) pyrimido [4',5':4,5] thieno (2,3-b)
      quinoline with DNA was studied by UV-Vis and fluorescence spectrophotometry as
      well as by hydrodynamic methods. On binding to DNA, the absorption spectra
      underwent bathochromic and hypochromic shifts and the fluorescence was quenched.
      These compounds are able to bind to DNA with an affinity of about 10(6) M(-1) for
      calf thymus DNA at ionic strength 0.01 M and their intercalating characteristic
      (lengthening of the DNA) depends upon the length of the chain. Binding to the GC
      rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf
      thymus DNA at ionic strength 0.01 M. The cytotoxicities of these compounds on
      leukemia HL-60, melanoma B16F10 and neuro 2a cells are quite similar and
      inhibition (IC50) is in the range of 0.992-3.968 microM. The anticancer efficacy
      against B16 melanoma, has provided evidence of major antitumor activity for 8
      methyl-4-(3diethylaminopropylamino) pyrimido [4',5':4,5] thieno(2,3-b)quinoline.
      Single or multiple intraperitonial (i.p) doses of drug proved high level activity
      against the subcutaneous (s.c) grafted B16 melanoma, significantly increasing
      survival (p<0.001) and inhibiting tumor growth (T/C of 4%). This study offers a
      new intercalation functional group to DNA-targeted drug design.

PMID- 14644569
TI  - Effects of ultraviolet B on epidermal morphology, shedding, lipid peroxide, and
      antioxidant enzymes in Cope's rat snake (Elaphe taeniura).
AB  - Cope's rat snakes (Elaphe taeniura) favor to expose under sunlight in order to
      increase their body temperature simultaneously increasing the risk of skin damage
      by ultraviolet B (UVB) irradiation. We have investigated the effects of UVB
      irradiation on their skin. Results show that the UVB transmission of the
      keratinous layer was only 5.1+/-0.36%. The peak of epidermal damage and
      malondialdehyde (MDA) content, a product of lipid peroxidation, simultaneously
      occurred 72-96, 48 or 24 h after exposure to 300, 500 and 800 mJ/cm2 of UVB
      radiation, respectively. Superoxide dismutase (SOD) activity was inhibited by UVB
      and the lowest activity occurred 24, 48, 12 and 12 h after exposure to 110, 300,
      500 and 800 mJ/cm2 of UVB, respectively. SOD activity recovered later to some
      extent but mostly remained below control level. After exposure to different doses
      of UVB radiation, catalase (CAT) activity was inhibited immediately, and then
      gradually recovered and even increased to peak levels above control level. The
      highest CAT levels accompanied the most serious damage of skin morphology. Later
      on, CAT activity decreased and recovered again close to or below control level,
      which was accompanied by shedding off the damaged epidermal complex. This
      indicated that the epidermal damage induced by UVB is closely related to lipid
      peroxidation, where CAT acts as a primary antioxidant enzyme. Moreover, the
      keratinous layer protects the viable cell layer against UVB damage as well.

PMID- 14644570
TI  - Photodegradation pathways and the in vitro phototoxicity of pyrazinamide, a
      phototoxic antitubercular drug.
AB  - The phototoxic antitubercular drug pyrazinamide (1) is photolabile under
      irradiation with UV-A light as well as with a N2 laser (at 337 nm) in aerobic
      conditions. Irradiation in methanolic and in aqueous solutions of 1 produces four
      and three photoproducts, respectively. Their formation involves primary alpha
      cleavage between the excited carbonyl of the amido group and the aromatic ring
      followed by hydrogen abstraction and dimerization. Pyrazinamide was able to cause
      photohemolysis in human erythrocytes and peroxidation of linoleic acid.
      Inhibition of both processes on addition of reduced glutathione (GSH) or ascorbic
      acid suggests the involvement of radicals. The absence of inhibition of the
      photohemolysis and lipid peroxidation processes in the presence of sodium azide
      (NaN3), or irradiation under argon, and the absence of singlet oxygen during the
      photolysis confirmed with 2,5-dimethylfuran rules out the possibility of
      participation of 1O2 in this process. Glutathione depletion was also observed. A
      radical intermediate was evidenced by thiobarbituric acid that was used as a
      radical probe, as well as by the dimerization of cysteine. No photohemolysis was
      detected in presence of the isolated photoproduct. We have also determined the
      relative efficiencies for the formation of single strand breaks after the
      irradiation of pBR322 DNA and pyrazinamide, which was also reduced in the
      presence of GSH.

PMID- 14644571
TI  - Identification of 6-aminochrysene photoproducts and study of the effect of a
      humic acid and riboflavin on its photolysis.
AB  - The effect of the photosensitizer riboflavin (0, 10, 25, 50, 100 microM) and a
      river humic acid (0, 20, 40, 80 ppm) on the photolysis of 6-aminochrysene (6AC)
      in 10 mM PBS solution (pH 7.0) was studied. The presence of riboflavin
      significantly enhanced photolysis rate of 6AC. The photo-transformation half-life
      of 6AC was 1 or 36 min, respectively, in the presence or absence of riboflavin.
      The humic acid inhibited the photo-transformation rate of 6AC. The photo
      transformation half-lives of 6AC were 37, 56, 92 min at 20, 40, 80 ppm humic
      acid, respectively. By using LC-MS, the main 6AC photoproduct identified was 5,6
      chrysene-quinone along with some minor products. Both 6AC and 5,6-chrysene
      quinone exhibited photoinduced cytotoxicity. A photochemical transformation
      pathway for 6AC was derived.

PMID- 14644572
TI  - Does fluorescence spectroscopy detect dimers of the polyene antibiotic
      amphotericin B?

PMID- 14644574
TI  - The use of FT-IR imaging as an analytical tool for the characterization of drug
      delivery systems.
AB  - FT-IR imaging spectroscopy is well suited for studying dynamic processes
      occurring in multi-component systems. Each component is resolved spatially based
      on the spectral response at each detector element. Additionally, the sequential
      collection of images tracks the movement of each component over time. In this
      study, the delivery characteristics of the drug, testosterone, suspended in a
      poly(ethylene oxide) (PEO) matrix was observed using this technique. Drug release
      occurred as the hydrophilic, erodible polymer underwent controlled dissolution,
      exposing the drug to the aqueous environment. The subsequent conversion of the
      drug into the therapeutic aqueous form completed the delivery process.
      Qualitative evaluation of the false color composite infrared images led to the
      elucidation of two distinct delivery mechanisms, dependent on the degree of drug
      loading. The spatially embedded spectral features led to the quantification of
      the drug release rates as well as the rates of polymer dissolution. The rates for
      both polymer dissolution and drug release were evaluated using well-established
      models. Additionally, the homogeneity of the drug dispersion for different
      loadings was characterized. The roles of chemical interactions across the solvent
      interface of species were also investigated. Changes in each component from the
      bulk to the solvated region were investigated, revealing changes in concentration
      and polymer orientation as well as inter-species interactions.

PMID- 14644575
TI  - A model for osmotic pressure driven release from cylindrical rubbery polymer
      matrices.
AB  - Osmotic pressure-driven drug release from rubbery polymer matrices in a
      cylindrical geometry has been shown to produce a period of nearly constant
      release. In order to explain this behavior and in an effort to produce a tool for
      device design, a mathematical model of the release was developed. The model was
      tested by application to literature data of the release of NaI from
      poly(dimethylsiloxane) cylinders and found to provide good agreement with the
      data. The model demonstrates that, although there is a decrease in solute
      concentration as one moves from the exterior to the center of the cylinder, a
      period of nearly constant release is produced, lasting until about 60% of the
      initial drug load has been released.

PMID- 14644576
TI  - In vivo biocompatibility and biodegradation of poly(ethylene carbonate).
AB  - Biodegradation and biocompatibility of poly(ethylene carbonate) (PEC) was
      examined using an in vivo cage implant system. Exudate analysis showed that PEC
      and PEC degradation products were biocompatible and induced minimal inflammatory
      and wound healing responses. Adherent foreign body giant cells (FBGCs) caused
      pitting on the PEC surface, which led to extensive degradation over time. Data
      obtained from molecular weight and examination of film cross-sections in the
      scanning electron microscope (SEM) indicated that PEC underwent surface erosion
      with no change to the remaining bulk. Attenuated total reflectance infrared (ATR
      FTIR) spectroscopy was used to characterize the chemical degradation. Superoxide
      anion released from inflammatory cells appeared to initiate an "unzipping"
      mechanism of degradation by deprotonation of PEC hydroxyl end groups. The
      resulting alkoxide ion participated in a concerted mechanism involving water and
      the carbonate carbonyl, leading to elimination of ethylene glycol. Carbonate ions
      decomposed further with release of carbon dioxide to regenerate alkoxide ion.

PMID- 14644577
TI  - Brain uptake of thiamine-coated nanoparticles.
AB  - Recently, a novel nanoparticle (NP) comprised of emulsifying wax and Brij 78 was
      shown to have significant brain uptake using the in-situ rat brain perfusion
      technique. To further these studies and to specifically target brain, we have
      incorporated thiamine as a surface ligand on the nanoparticles. Solid
      nanoparticles were prepared from oil-in-water microemulsion precursors.
      Nanoparticles were radiolabeled and a thiamine ligand (thiamine linked to
      distearoylphosphatidylethanolamine via a polyethylene glycol spacer) was coated
      on the surface of the nanoparticles. Initial experiments focused on assessing
      uptake of [3H]nanoparticles with and without thiamine surface ligands.
      Biodistribution nanoparticle studies were also carried out in BALB/c mice. The
      results showed: (1) the effectiveness of using microemulsions as precursors to
      engineer nanoparticles, (2) kinetic modeling for brain uptake of nanoparticles
      with and without the thiamine surface ligands, and (3) initial data suggesting
      mechanisms for nanoparticle brain entry. Comparison of NP brain uptake
      demonstrated that the thiamine-coated nanoparticle associated with the blood
      brain barrier (BBB) thiamine transporter and had an increased K(in) between 45
      and 120 s (thiamine coated NP 9.8 +/- 1.1 x 10(-3) ml/s/g versus uncoated NPs;
      7.0 +/- 0.3 x 10(-3) ml/s/g). It was concluded that the thiamine ligand
      facilitated binding and/or association with blood-brain barrier thiamine
      transporters, which may be a viable mechanism for nanoparticle mediated brain
      drug delivery.

PMID- 14644578
TI  - Pharmacokinetics of methotrexate in rabbit skin and plasma after iv-bolus and
      iontophoretic administrations.
AB  - The pharmacokinetics of methotrexate (MTX) in rabbit's skin and plasma after iv
      bolus and iontophoretic delivery at different current densities was studied.
      Linear microdialysis probes were introduced into the upper dorsal shaved skin of
      tranquilized rabbits. Commercially available patches were used to deliver MTX for
      1 h at different current densities (100, 200, and 300 microA/cm2) on different
      occasions. Iv-boluses (10 mg/kg) of MTX were also administered. Retrodialysis was
      performed at the end of the experiments to estimate probe recovery. Plasma and
      microdialysis samples were analyzed using a validated HPLC assay. Following iv
      bolus, MTX showed a bi-exponential decay both in plasma and in skin. Cmax in skin
      occurred with a delay of 22 min compared with plasma. No quantifiable
      concentration of MTX was detected in the skin on passive drug delivery. Systemic
      exposure to MTX (AUC) and Cmax increased linearly with current density.
      Nevertheless, exposure to MTX in the skin did not increase linearly with current
      density, whereas Cmax did. In conclusion, iontophoresis remarkably improved the
      dermal delivery of MTX over passive diffusion. However, total exposure did not
      increase with current density in the skin, suggesting that for local applications
      lower current densities may achieve the same effects with minimal systemic
      exposure.

PMID- 14644579
TI  - Oral colon-specific drug delivery for bee venom peptide: development of a coated
      calcium alginate gel beads-entrapped liposome.
AB  - Colon-specific drug delivery systems (CDDSs) can be used to improve the
      bioavailability of protein and peptide drugs through the oral route. A novel
      formulation for oral administration using coated calcium alginate gel beads
      entrapped liposome and bee venom peptide as a model drug has been investigated
      for colon-specific drug delivery in vitro. Drug release studies under conditions
      mimicking stomach to colon transit have shown that the drug was protected from
      being released completely in the physiological environment of the stomach and
      small intestine. The release rate of bee venom from the coated calcium alginate
      gel beads-entrapped liposome was dependent on the concentration of calcium and
      sodium alginate, the amount of bee venom in the liposome, as well as the coating.
      Furthermore, a human gamma-scintigraphy technique was used in vivo to determine
      drug delivery more precisely. The colonic arrival time of the tablets was found
      to be 4-5 h. The results clearly demonstrated that the coated calcium alginate
      gel beads-entrapped liposome is a potential system for colon-specific drug
      delivery.

PMID- 14644580
TI  - A density-functional model for controlled release.
AB  - Polymer diffusion based on density-functional theory is applied to controlled
      release systems. These models explicitly treat the multiphase characteristics of
      biomolecule-polymer composites typical of drug delivery devices. Polymer
      diffusion was modeled using the modified Cahn-Hilliard equation with periodic
      boundary conditions in one dimension and near-zero concentration boundaries in
      the second dimension. The diffusional driving forces are differences in chemical
      potential based in part on the Flory-Huggins free energy of mixing in polymer
      systems rather than concentration gradients. Release rates from this model were
      compared to exponential models typically used in the drug delivery literature.
      Simulations based on this model showed that the diffusional exponent is 1/2; this
      exponent is consistent with Fickian models at early times. Particle growth, which
      also occurs in diffusing, dispersed systems, was observed. The particle growth
      exponent in these systems was 2/3, twice the value typical in bulk ripening
      systems. The increased growth rate was caused by the elimination of small
      particles due to diffusion out of the system, which removed the low particle size
      region of the distribution faster than ripening alone.

PMID- 14644581
TI  - Development and evaluation of bio-dissolution systems capable of detecting the
      food effect on a polysaccharide-based matrix system.
AB  - Methods are proposed and tested for mimicking the in vitro food effect on
      controlled release dosage forms, using USP dissolution apparatus 3. Using in vivo
      data a pH and time profile was constructed, and the methods utilized either
      presoaking in peanut oil or continuous oil contact to mimic the presence of a
      high fat meal. A water soluble drug (propranolol hydrochloride, class 1 by BCS)
      was used as a model material. Both methods were able to confirm that a labile
      multiparticulate system (Inderal LA) was susceptible to such in vitro effects. A
      hydrocolloid matrix tablet showed low susceptibility to either technique. There
      was a good correlation between methods, which may indicate that the oil
      presoaking method, which is less time consuming to carry out and leads to more
      simple subsequent analysis, may be sufficient to identify dosage forms
      susceptible to physical food effects.

PMID- 14644582
TI  - Controlled release of estradiol solubilized in carbopol/surfactant aggregates.
AB  - The potential of carbopol/surfactant dispersions as solubilizing and controlled
      release systems of estradiol (a poorly water-soluble drug) was evaluated. The
      solubilization of estradiol in the dispersions of Carbopol 934 (0.25%) and
      Pluronic F-127, Tween 80, sodium dodecylsulfate (SDS), or benzalkonium chloride
      (BkCl) was assessed, by differential scanning calorimetry (DSC) of films obtained
      by desiccation, as a decrease in estradiol melting temperature and enthalpy. The
      amounts of estradiol solubilized in carbopol/SDS and carbopol/Tween 80 aqueous
      dispersions were considerably greater (solubilization capacity: 1.3 and 9 times
      greater) than in the surfactant alone solutions and up to 100 times greater than
      in water. High aggregates/water equilibrium partition coefficients of estradiol
      in carbopol/SDS (1768 M(-1)) and carbopol/Tween 80 (14114 M(-1)) dispersions were
      found. Carbopol/(1%) SDS/(25 mg/dl) estradiol and carbopol/(0.1%) Tween 80/(5
      mg/dl) estradiol dispersions had a pH of around 4, were easy flowing, and showed
      sustained release for at least 1 week. Estradiol diffusion coefficients were
      greater when the receptor medium was 0.3-1.0% SDS solution than when it was iso
      osmotic NaCl solution or pH 7.5 phosphate buffer. At this pH, a viscoelastic gel
      is formed on the donor side of the membrane and the drug diffusion slowed down.
      When the receptor medium contains a surfactant, estradiol release seems to happen
      as a direct exchange between the carbopol/surfactant aggregates and the receptor
      surfactant micelles. If no surfactant is in the receptor fluid,
      estradiol/surfactant complexes migrate towards the receptor. Despite the low
      viscosity of these dispersions, estradiol diffusion coefficients were in the same
      order of magnitude as those obtained with a commercially available neutralized
      ethanol/water carbopol gel of estradiol (60 mg/dl). When the receptor medium had
      no surfactant, the low affinity of estradiol for water prevented drug diffusion
      from the commercial formulation. In summary, carbopol/surfactant aggregates act
      as efficient carriers of hydrophobic drugs; the affinity of estradiol for
      carbopol/surfactant aggregates, their dissociation, and the diffusivity of
      estradiol/surfactant complexes being key factors in the control of the drug
      release process.

PMID- 14644583
TI  - A pulsatile drug delivery system based on rupturable coated hard gelatin
      capsules.
AB  - The objective of this study was to develop and evaluate a pulsatile drug delivery
      system based on drug-containing hard gelatin capsules, which were coated with a
      swelling layer and an outer insoluble, water-permeable polymeric coating. An
      inner pressure developed by the swelling layer resulted in the rupture of the
      outer coating. Preliminary studies with a simulated rupture test demonstrated the
      dependence of the lag time prior to rupture on the properties of the coating,
      such as its water permeability and mechanical strength. The lag time increased
      with a higher coating level, but decreased with the addition of the hydrophilic
      pore former, hydroxypropyl methylcellulose. Increasing the amount of the swelling
      layer decreased the lag time. The coated capsules took up release medium at a
      nearly constant rate until a critical maximum was reached, where the swelling
      pressure was sufficient to rupture the outer coating. The rate of medium uptake
      decreased with increasing coating level, while the extent of medium uptake was
      almost the same for the different coating levels. A hydrophobic particulate
      material, magnesium stearate, was added to the coating layer to reduce the
      mechanical strength and therefore the lag time. The test conditions, such as
      surfactant addition to the release medium or floating vs. complete immersion of
      capsules in the medium, affected the lag time.

PMID- 14644584
TI  - Ciprofloxacin implants for bone infection. In vitro-in vivo characterization.
AB  - To elucidate the antibiotic release mechanism from implants composed of calcium
      phosphates (hydroxyapatite [HAP] and tricalcium phosphate [TCP]), 30 kDa poly(DL
      lactide) (PLA-30) and ciprofloxacin (CFX), nine formulations were prepared. In
      vitro results show that the release rate decreased as compression load and
      PLA/phosphates ratio increased. In contrast, a slower percent release rate was
      observed with higher drug loading. Swelling-erosion-disintegration of the
      implants was observed during the release assays, due to CFX swelling. Two CFX
      implant formulations were selected for implantation in the femur of rabbits,
      according to in vitro results. The implant drug loads tested were 10% and 40% of
      CFX. The in vivo results showed that the antibiotic concentrations achieved
      throughout the femur were higher for 4 weeks than the minimum inhibitory
      concentrations (MIC) against the most common of the pathogens that cause
      osteomyelitis. The CFX-10% implant was considered the best formulation as CFX was
      totally released within 6 weeks, and therapeutic bone levels were achieved, and
      the histological and radiographic analyses showed the osteoconductive properties
      of the materials. All these results showed that CFX release is limited by its
      solubility, and the erosion-disintegration and bone ingrowth into the implants
      enhanced the antibiotic release.

PMID- 14644585
TI  - The influence of drug incorporation on the structure and release properties of
      solid dispersions in lipid matrices.
AB  - The effect of incorporating caffeine and paracetamol on the structure and
      behaviour of Gelucire 50/13 has been studied with a view to establishing whether
      the choice of drug influences the solid structure and release mechanism.
      Dispersions containing up to 30% w/w drug were prepared and studied using
      differential scanning calorimetry (DSC), hot stage differential interference
      contrast microscopy (HSM), dissolution studies and erosion, water uptake (WU) and
      diameter change measurements. Gelucire 50/13 alone showed a broad melting
      endotherm using DSC, with two dominant peaks at 36 and 44 degrees C. While
      incorporation of caffeine did not result in marked changes to the profile, the
      presence of paracetamol increased the proportion of material in the lower melting
      peak. HSM studies indicated that the Gelucire crystallised into two main
      spherulitic conformations; paracetamol appeared to act as a nucleation site for
      the lower melting fractions while caffeine particles changed into a needle-shaped
      morphology on cooling the system from the liquid state. Dissolution studies at 37
      degrees C showed the caffeine to be released at a relatively faster rate than the
      paracetamol. Kinetic modeling and direct measurement of the erosion profile
      indicated that the caffeine systems showed a greater preponderance for erosion
      than did the corresponding paracetamol systems. It is suggested that the
      paracetamol promotes the generation of the lower melting form of Gelucire 50/13
      which in turn influences the release rate and mechanism. The study therefore
      indicates that the influence of the drug should be carefully considered when
      studying Gelucire matrix systems.

PMID- 14644586
TI  - Cutaneous absorption and elimination of three acyclic terpenes--in vitro studies.
AB  - The purpose of the study was to investigete skin absorption and elimination of
      three acyclic terpenes: citronellol (C), linalool (L) and linalyl acetate (LA).
      The pure terpenes were applied onto the human skin in vitro, and after 1-4 h,
      their content in the stratum corneum layers and in the epidermis/dermis was
      determined using gas chromatography. Similarly, the amounts of terpenes in the
      skin were analysed during 4 h following 1-h absorption. Good absorption to the
      all skin layers was demonstrated as soon as after 1 h: the total skin cumulation
      of L, LA and C was 827, 124 and 954 microg/cm2, respectively. A self-promoting
      absorption was observed for L, since the amount of this terpene analysed in the
      stratum corneum after 1 h was 78.3, rising to 479 microg/cm2 after 4 h. During
      the elimination phase, a constant drop in the total amount in the skin was
      observed only for C, while the total skin content of L and LA did not change,
      although diffusion from the stratum corneum to epidermis/dermis occurred. The log
      P values of the terpenes were calculated using three different programs, but
      generally, neither absorption nor elimination can be directly correlated with the
      physicochemical parameters, despite of the fact that the least absorption was
      observed for the most lipophilic LA.

PMID- 14644587
TI  - Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model.
AB  - Cannabidiol (CBD) is a new drug candidate for treatment of rheumatic diseases.
      However, its oral administration is associated with a number of drawbacks. The
      objective of this study was to design a transdermal delivery system for CBD by
      using ethosomal carriers. CBD ethosomes were characterized by transmission
      electron microscopy, confocal laser scanning microscopy and differential scanning
      calorimetry. Results indicated that CBD and phosphatidylcholine form an eutectic
      mixture. In vivo application of ethosomal CBD to CDI nude mice produced a
      significant accumulation of the drug in the skin and in the underlying muscle.
      Upon transdermal application of the ethosomal system to the abdomen of ICR mice
      for 72 h, steady-state levels were reached at about 24 h and lasted at least
      until the end of the experiment, at 72 h. Furthermore, transdermal application of
      ethosomal CBD prevented the inflammation and edema induced by sub-plantar
      injection of carrageenan in the same animal model. In conclusion, ethosomes
      enable CBD's skin permeation and its accumulation in a depot at levels that
      demonstrate the potential of transdermal CBD to be used as an anti-inflammatory
      treatment.

PMID- 14644588
TI  - Efficient gene delivery by urocanic acid-modified chitosan.
AB  - Nonviral delivery systems for gene therapy have been increasingly proposed as
      safer alternatives to viral vectors. Chitosan is considered to be a good
      candidate for the gene delivery system since it is already known as a
      biocompatible, biodegradable, and low toxic material with high cationic charge
      potential. However, the use of chitosan for gene delivery is limited due to low
      transfection efficiency. To enhance the transfection efficiency, water-soluble
      chitosan (WSC) was coupled with urocanic acid (UA) bearing imidazole ring which
      can play the crucial role in endosomal rupture through proton sponge mechanism.
      The urocanic acid-modified chitosan (UAC) was complexed with DNA, and UAC/DNA
      complexes were characterized. The sizes of UAC/DNA complexes under physiological
      condition (109-342 nm) were almost same as those of chitosan-DNA complexes. UAC
      also showed good DNA binding ability, high protection of DNA from nuclease
      attack, and low cytotoxicity. The transfection efficiency of chitosan into 293T
      cells was much enhanced after coupling with UA and increased with an increase of
      UA contents in the UAC.

PMID- 14644589
TI  - Preparation and evaluation of a new class of gene transfer reagents: poly(
      alkylaminosiloxanes).
AB  - We report the evaluation of poly(-alkylaminosiloxane) as a novel class of
      polycationic DNA carriers. Controlled hydrolysis of mono- and di
      aminoalkylmethyldimethoxysilane provided a wide range of defined oligomeric
      mixtures. Basic hydrolysis conditions yielded mixtures composed mainly of cyclic
      and long linear oligomers, while under acidic conditions mainly short-linear
      oligomers were derived. They all efficiently interacted with plasmid DNA as
      revealed by electron microscopy and DNA retardation assays. However, only diamine
      based oligomers prepared under basic conditions were able to mediate substantial
      levels of DNA transfection in human HeLa cells. SiDA1b, prepared by basic
      hydrolysis of 3-(2-aminoethylamino)propyl-methyl-dimethoxysilane, was found to be
      at least as efficient as the frequently used cationic transfection agents DOTAP
      and polyethylenimine (PEI). The transfection activity was sensitive to
      bafilomycin A1, suggesting a mechanism that depends on proton capture during the
      acidification process associated with endocytosis.

PMID- 14644593
TI  - Effects of liner stiffness for trans-tibial prosthesis: a finite element contact
      model.
AB  - The socket liner plays a crucial role in redistribution of the interface stresses
      between the stump and the socket, so that the peak interface stress could be
      reduced. However, how the peak stress is affected by various liner stiffnesses is
      still unknown, especially when the phenomenon of the stump slide within the
      socket is considered. This study employed nonlinear contact finite element
      analyses to study the biomechanical reaction of the stump sliding with particular
      attention to the liner stiffness effects of the trans-tibial prosthesis. To
      validate the finite element outcomes, experimental measurements of the interface
      stresses and sliding distance were further executed. The results showed that the
      biomechanical response of the stump sliding are highly nonlinear. With a less
      stiff liner, the slide distance of the stump would increase with a larger contact
      area. However, this increase in the contact area would not ensure a reduction in
      the peak interface stress and this is due to the combined effects of the non
      uniform shape of the socket and the various sliding distances generated by the
      different liner stiffnesses.

PMID- 14644594
TI  - Combination of finite element modeling and optimization for the study of lumbar
      spine biomechanics considering the 3D thorax-pelvis orientation.
AB  - A model of the lumbar spine capable of taking into account realistic loads
      derived from human activity would be of great benefit in studying its normal
      biomechanical functioning as well as its in vivo behavior in injured and
      surgically altered states. This paper proposes a method to analyze the mechanical
      response of the lumbar spine subjected to loads derived from human activity,
      combining a non-linear finite element model (FEM) and an optimization-based force
      predicting algorithm. Loads borne by the lumbar spine at the T12-L1 level (joint
      loads) are first predicted with the optimization algorithm and then applied to
      the FEM, while a boundary condition prescribing the relative L1-sacrum rotation
      is imposed onto the FEM to account for three-dimensional physiological thorax
      pelvis orientation. The prescribed rotation is achieved through the application
      of moments on L1. To account for the effect of these moments on lumbar joint
      loads, an iteration between the optimization technique and the FEM computation
      has been carried out. This method provides two main benefits over previous
      studies: first, it allows for the application of any 3D loading condition while
      considering the real 3D rotation measured between the thorax and the pelvis, and
      second, it makes it possible to estimate the moments that must be applied on L1
      in order to maintain this rotation, taking them into account when predicting
      joint loads. As an example application of the method, results are presented for
      the lumbar spine mechanical response at the time of peak T12-L1 joint force
      during walking.

PMID- 14644595
TI  - Local and regional wave speed in the aorta: effects of arterial occlusion.
AB  - Arterial wave speed is widely used to determine arterial distensibility and has
      been utilised as a surrogate marker for vascular disease. A comparison between
      the results of the traditional foot-to-foot method for measuring wave speed to
      those of the pressure-velocity loop (PU-loop) method is one of the primary
      objectives of this paper. We also investigate the regional wave speed along the
      aorta, and the effect of arterial occlusion on the PU-loop measured in the
      ascending aorta. In 11 anaesthetised dogs, a total occlusion lasting 3 min was
      produced at four sites: upper thoracic, diaphragm, abdominal and left iliac
      artery. Pressure and flow in the ascending aorta and pressure proximal to the
      occlusion site were measured, and data were collected before, during the
      occlusion and after the occlusion had been removed. In control conditions, the
      wave speeds determined by the PU-loop in the aortic root were systematically
      lower than those measured by the foot-to-foot method. During thoracic and
      diaphragm occlusions, mean aortic pressure and wave speed increased significantly
      but returned to control values after each occlusion had been removed. The PU-loop
      is an objective and easy to use method for determining wave speed and can be
      advantageous for use in short arterial segments when local measurements of
      pressure and velocity are available.

PMID- 14644596
TI  - Haemodynamics and mechanics following partial left ventriculectomy: a computer
      modeling analysis.
AB  - Mechanics following partial left ventriculectomy is still poorly understood. A
      computational cylindrical model of the left ventricle was developed, based on the
      myocardial fibre behaviour for the evaluation of the mechanical and
      haemodynamical effects of the operation. A healthy left ventricle with
      physiological geometry and function and a dilated hypokinetic heart were
      investigated. Haemodynamic and mechanical data were obtained at baseline and
      compared with those obtained at different degrees of volume reduction. Data
      included: ejection fraction (EF); stroke volume (SV); end-systolic and end
      diastolic pressure-volume relationships (ESPVR and EDPVR), and efficiency. EF
      increases following volume reduction in both simulation but, concurrently, SV
      shows modest improvement (dilated ventricle) or reduction (healthy ventricle) at
      progressive degrees of resection. The ESPVR and EDPVR slope increases and shifts
      leftward with the resection extent, but the increase of the ESPVR slope is more
      pronounced in dilated ventricle. Efficiency is improved in the dilated heart
      after resections, while does not improve when the healthy-heart volume is
      reduced. The simulation of partial left ventriculectomy suggests an improvement
      of systolic performance, counterbalanced by increased diastolic stiffness
      following inverse remodelling. Efficiency of simulated dilated ventricles is
      enhanced by volume reduction, suggesting a favourable effect of reduction of the
      metabolic demand of the failing heart.

PMID- 14644597
TI  - Neural network modelling of dynamic cerebral autoregulation: assessment and
      comparison with established methods.
AB  - A time lagged recurrent neural network (TLRN) was implemented to model the
      dynamic relationship between arterial blood pressure (ABP) and cerebral blood
      flow velocity (CBFV) and its performance was compared to classical linear model
      such as transfer function analysis, Aaslid's dynamic autoregulation model, and
      the Wiener-Laguerre moving average filter. A simple linear regression was also
      tested as a naive estimator. In 16 normal subjects, CBFV was continuously
      recorded with Doppler ultrasound and ABP with the Finapres device during six
      repeated thigh cuff manoeuvres. Using mean beat-to-beat values of ABP as input
      and CBFV as output, the performance of each method was assessed by the model's
      predicted velocity correlation coefficient and normalized mean square error
      (MSE). Cross-validation was performed using three thigh cuff manoeuvres for the
      training data set and the other three for the validation set. The four methods
      studied performed significantly better than the zero-order naive estimator. The
      TLRN performed better than transfer function analysis, but was not significantly
      different from the time-domain techniques, despite showing the minimum predictive
      MSE. CBFV step responses could be extracted from the TLRN showing the presence of
      non-linear behaviour both in terms of amplitude and directionality.

PMID- 14644598
TI  - Evaluation of the efficiency of venous leg ulcer treatment with a membrane
      dressing.
AB  - A quantitative method for the evaluation of ulcer healing has been developed. The
      method consists of calculating an ulcer healing efficiency ratio (zetaz)
      interpreted as the second derivative of the regenerated ulcer area over time. The
      zetaz value is in direct proportion to the acceleration of healing, and in
      inverse proportion to the initial ulcer area. In order to test this method, we
      measured the surface area that was delimited by the ulcer edge and the initial
      depth of the ulcer in three patient groups. The first and third groups were
      treated with a cellulose membrane and the second group-with Unna boot. The
      initial ulcer area was the same in groups 1 and 2, but in group 3, it was six
      times smaller. The greatest zetaz value was obtained in group 3, the smallest-in
      group two.

PMID- 14644599
TI  - An improved method for the automatic mapping of computed tomography numbers onto
      finite element models.
AB  - The assignment of bone tissue material properties is a fundamental step in the
      generation of subject-specific finite element models from computed tomography
      data. Aim of the present work is to investigate the influence of the material
      mapping algorithm on the results predicted by the finite element analysis. Two
      models, a coarse and a refined one, of a human ileum, femur and tibia, were
      generated from CT data and used for the tests. In addition a convergence analysis
      was carried out for the femur model, using six refinement levels, to verify
      whether the inclusion of the material properties would significantly alter the
      convergence behaviour of the mesh. The results showed that the choice of the
      mapping algorithm influences the material distribution. However, this did not
      always propagate into the finite element results. The difference between the
      maximum Von Mises stress remained always lower than 10%, apart one case when it
      reached the 13%. However, the global behaviour of the meshes showed more marked
      differences between the two algorithms: in the finer meshes of the two long bones
      20-30% of the bone volume showed differences in the predicted Von Mises stresses
      greater than 10%. The convergence behaviour of the model was not worsened by the
      introduction of inhomogeneous material properties. The software was made
      available in the public domain.

PMID- 14644600
TI  - Segmentation of magnetic resonance images using a combination of neural networks
      and active contour models.
AB  - Segmentation of medical images is very important for clinical research and
      diagnosis, leading to a requirement for robust automatic methods. This paper
      reports on the combined use of a neural network (a multilayer perceptron, MLP)
      and active contour model ('snake') to segment structures in magnetic resonance
      (MR) images. The perceptron is trained to produce a binary classification of each
      pixel as either a boundary or a non-boundary point. Subsequently, the resulting
      binary (edge-point) image forms the external energy function for a snake, used to
      link the candidate boundary points into a continuous, closed contour. We report
      here on the segmentation of the lungs from multiple MR slices of the torso; lung
      specific constraints have been avoided to keep the technique as general as
      possible. In initial investigations, the inputs to the MLP were limited to
      normalised intensity values of the pixels from an (7 x 7) window scanned across
      the image. The use of spatial coordinates as additional inputs to the MLP is then
      shown to provide an improvement in segmentation performance as quantified using
      the effectiveness measure (a weighted product of precision and recall). Training
      sets were first developed using a lengthy iterative process. Thereafter, a novel
      cost function based on effectiveness is proposed for training that allows us to
      achieve dramatic improvements in segmentation performance, as well as faster, non
      iterative selection of training examples. The classifications produced using this
      cost function were sufficiently good that the binary image produced by the MLP
      could be post-processed using an active contour model to provide an accurate
      segmentation of the lungs from the multiple slices in almost all cases, including
      unseen slices and subjects.

PMID- 14644601
TI  - Application of adaptive noise cancellation with neural-network-based fuzzy
      inference system for visual evoked potentials estimation.
AB  - This paper presents an application of adaptive noise cancellation with neural
      network-based fuzzy inference system (NNFIS) for rapid estimation of visual
      evoked potentials (VEPs). Usually a recorded VEP is severely contaminated by
      background ongoing activities of the spontaneous EEG signal in the human brain.
      Many approaches have been adopted to enhance the signal-to-noise ratio (SNR) of
      the recorded signal. However, nonlinear dynamic methods are rarely investigated
      in view of their complexity, and the fact that the nonlinear characteristics of
      the signal are hard to determine in general. An adaptive noise cancellation
      method with NNFIS was carefully designed to estimate the VEP signal. NNFIS, based
      on Takagi and Sugeno's fuzzy model, has the advantage of being linear-in
      parameter; thus the conventional adaptive methods can be efficiently utilized to
      estimate its parameters. Another advantage of NNFIS lies in that it can track the
      dynamic behavior of VEP in a real-time fashion because the VEP variation tracking
      is important for critical patient monitoring in the clinical situation. A series
      of computer experiments conducted on simulated and real-test responses have
      confirmed the superiority of the method developed in this paper.

PMID- 14644602
TI  - Clinical isolates of GB virus type C vary in their ability to persist and
      replicate in peripheral blood mononuclear cell cultures.
AB  - GB virus C/hepatitis G virus (GBV-C) replication in vitro is inefficient and
      inconsistent. In this study, clinical isolates of GBV-C were evaluated using
      peripheral blood mononuclear cell (PBMC) based culture methods. Isolates varied
      consistently in their ability to persistently replicate, and yield increased in
      cells grown without PHA/IL-2 stimulation. The deduced polyprotein sequence of an
      isolate that replicated well was determined (GenBank AY196904) and compared to 20
      full-length GBV-C sequences. Fourteen of the 16 unique amino acid polymorphisms
      identified were in the coding regions for nonstructural proteins associated with
      interferon resistance and RNA replication. These data indicate that clinical GBV
      C isolates vary in their ability to persist in culture, do not require PHA/IL-2
      stimulation, and that sequence variability in key regulatory regions may affect
      growth in PBMC cultures. Since GBV-C appears to inhibit HIV replication in a
      coinfection model, these studies should facilitate determination of the mechanism
      of this interaction.

PMID- 14644603
TI  - A macrophage inflammatory protein homolog encoded by guinea pig cytomegalovirus
      signals via CC chemokine receptor 1.
AB  - Cytomegaloviruses encode homologs of cellular immune effector proteins, including
      chemokines (CKs) and CK receptor-like G protein-coupled receptors (GPCRs).
      Sequence of the guinea pig cytomegalovirus (GPCMV) genome identified an open
      reading frame (ORF) which predicted a 101 amino acid (aa) protein with homology
      to the macrophage inflammatory protein (MIP) subfamily of CC (beta) CKs,
      designated GPCMV-MIP. To assess functionality of this CK, recombinant GPCMV-MIP
      was expressed in HEK293 cells and assayed for its ability to bind to and
      functionally interact with a variety of GPCRs. Specific signaling was observed
      with the hCCR1 receptor, which could be blocked with hMIP -1alpha in competition
      experiments. Migration assays revealed that GPCMV-MIP was able to induce
      chemotaxis in hCCR1-L1.2 cells. Antisera raised against a GST-MIP fusion protein
      immunoprecipitated species of approximately 12 and 10 kDa from GPCMV-inoculated
      tissue culture lysates, and convalescent antiserum from GPCMV-infected animals
      was immunoreactive with GST-MIP by ELISA assay. These results represent the first
      substantive in vitro characterization of a functional CC CK encoded by a
      cytomegalovirus.

PMID- 14644604
TI  - Alpha-dystroglycan can mediate arenavirus infection in the absence of beta
      dystroglycan.
AB  - Dystroglycan (DG) is a highly versatile cell surface molecule that provides a
      molecular link between the extracellular matrix (ECM) and the actin-based
      cytoskeleton. Encoded by a single gene, DG is posttranslationally processed to
      form alpha-DG, a peripheral protein identified as the cellular receptor for
      lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus (LFV), and the
      membrane-spanning subunit beta-DG. The link of beta-DG to the actin-based
      cytoskeleton and its association with the cellular signal transduction network
      suggest that it may function as an essential cofactor for the activity of alpha
      DG as a virus receptor. To address this issue, we constructed a deletion mutant
      lacking the cytoplasmic domain of beta-DG and a C-terminal fusion between alpha
      DG and the transmembrane domain of PDGF receptor. Both mutants were functional as
      virus receptors, indicating that beta-DG does not act as a cofactor with alpha-DG
      for arenavirus binding and entry. These observations are in agreement with the
      fact that LCMV infection is independent from the structural integrity of the
      actin-based cytoskeleton and suggest that alpha-DG functions primarily in the
      attachment of arenaviruses to the cell surface.

PMID- 14644605
TI  - Differential function and expression of the viral inhibitor of caspase 8-induced
      apoptosis (vICA) and the viral mitochondria-localized inhibitor of apoptosis
      (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses.
AB  - Human cytomegalovirus (CMV) genes UL36 and UL37 encode viral inhibitor of caspase
      8-induced apoptosis (vICA) and viral mitochondria inhibitor of apoptosis (vMIA),
      respectively. Rhesus macaque CMV homologues, denoted Rh-vICA and Rh-vMIA, were
      identified and found to suppress apoptosis. One of these functions was conserved
      in MCMV, encoded by the M36 gene and denoted M-vICA. Conserved regions were
      compared to domains important to vICA- and vMIA-mediated cell death suppression.
      The conserved sequences of primate CMV vMIA homologues overlapped with the two
      known functional domains, providing further evidence supporting a crucial role of
      vMIA in cell death suppression. RNA blot analyses revealed that expression of
      murine and rhesus macaque CMV UL36 and UL37 homologues started early and
      continued through late times of infection. Murine CMV homologues were expressed
      with alpha (immediate early) kinetics, like human CMV UL36 and UL37, whereas
      rhesus macaque CMV homologues exhibited beta (delayed early) kinetics. Despite
      differences in organization and transcriptional regulation, this region appears
      to carry out a conserved role in cell death suppression. When viewed in light of
      sequence conservation, a functional vMIA homologue appears to be encoded by every
      primate CMV, whereas a functional vICA homologue appears to be encoded by all
      cytomegaloviruses for which sequence data are available.

PMID- 14644606
TI  - Completion of trimeric hairpin formation of influenza virus hemagglutinin
      promotes fusion pore opening and enlargement.
AB  - For influenza virus hemagglutinin, an N-cap structure, created at low pH,
      interacts with membrane-proximal residues (173-178), bringing fusion peptides and
      membrane-spanning domains close together. Mutational analysis was used to define
      the role of these interactions in membrane fusion. For all N-cap mutants, both
      lipid and aqueous dye spread was greatly reduced. Mutation at residues that
      interact with the N-cap did not reduce levels of fusion, except for substitutions
      made at residue I173. For N-cap and I173 mutants, the addition of chlorpromazine
      greatly promoted transfer of aqueous dye. Electrical capacitance measurements
      confirmed that fusion pores usually did not form for the I173 mutants. Thus,
      neither N-cap formation nor interactions with segment 173-178 are needed for
      hemifusion, but are required for reliable formation and enlargement of the fusion
      pore. It is proposed that binding of I173 into a deep hydrophobic cavity within
      the coiled-coil promotes the transition from hemifusion to fusion.

PMID- 14644607
TI  - The prophage sequences of Lactobacillus plantarum strain WCFS1.
AB  - The Lactobacillus plantarum commensal WCFS1 contains four prophage elements in
      its genome. Lp1 and Lp2 are two about 40-kb-long uninducible prophages that share
      closely related DNA packaging, head and tail genes defining a second lineage of
      pac-site Siphoviridae in L. plantarum, distinct from L. plantarum phage phig1e,
      but related to Bacillus phage SPP1 and Lactococcus phage TP901-1. Northern
      analysis revealed transcribed prophage genes exclusively near both attachment
      sites. Comparative genomics identified candidate lysogenic conversion genes (LCG)
      downstream of the lysis cassette and within the lysogeny module. Notable are
      genes with sequence similarities to putative LCG from Streptococcus pyogenes
      prophages and to a Bacillus plasmid. Both prophages harbored tRNA genes. R-Lp3
      and R-Lp4 represent short prophage remnants; R-Lp3 abuts Lp2 and displays
      sequence links to cos-site Siphoviridae.

PMID- 14644608
TI  - Characterization of vnr-13, the first alphaherpesvirus gene of the bcl-2 family.
AB  - The Bcl-2 family, including antiapoptotic and proapoptotic members, plays key
      regulating roles in programmed cell death. We report the characterization of a
      new member of the bcl-2 family, encoded by herpesvirus of turkeys (HVT). The
      product of this gene shares 80% homology with Nr-13, an apoptosis inhibitor,
      which is overexpressed in avian cells transformed by the v-src oncogene. This new
      gene, that we propose to call vnr-13, is the first member of the bcl-2 family to
      be isolated among alpha-herpesviruses. Results from cells expressing the HVT-vnr
      13 gene product show that the encoded protein inhibits apoptosis and also reduces
      the rate of cellular proliferation. Contrary to all bcl-2 homologues found in
      gamma-herpesvirus, which are intronless, vnr-13 has the same organization as the
      cellular nr-13 gene. Hence, the HVT vnr-13 gene may have been acquired from a
      reverse transcriptase product of an unspliced precursor RNA, or via direct
      recombination with the host chromosomal DNA.

PMID- 14644609
TI  - Release of canine parvovirus from endocytic vesicles.
AB  - Canine parvovirus (CPV) is a small nonenveloped virus with a single-stranded DNA
      genome. CPV enters cells by clathrin-mediated endocytosis and requires an acidic
      endosomal step for productive infection. Virion contains a potential nuclear
      localization signal as well as a phospholipase A(2) like domain in N-terminus of
      VP1. In this study we characterized the role of PLA(2) activity on CPV entry
      process. PLA(2) activity of CPV capsids was triggered in vitro by heat or acidic
      pH. PLA(2) inhibitors inhibited the viral proliferation suggesting that PLA(2)
      activity is needed for productive infection. The N-terminus of VP1 was exposed
      during the entry, suggesting that PLA(2) activity might have a role during
      endocytic entry. The presence of drugs modifying endocytosis (amiloride,
      bafilomycin A(1), brefeldin A, and monensin) caused viral proteins to remain in
      endosomal/lysosomal vesicles, even though the drugs were not able to inhibit the
      exposure of VP1 N-terminal end. These results indicate that the exposure of N
      terminus of VP1 alone is not sufficient to allow CPV to proliferate. Some other
      pH-dependent changes are needed for productive infection. In addition to blocking
      endocytic entry, amiloride was able to block some postendocytic steps. The
      ability of CPV to permeabilize endosomal membranes was demonstrated by feeding
      cells with differently sized rhodamine-conjugated dextrans together with the CPV
      in the presence or in the absence of amiloride, bafilomycin A(1), brefeldin A, or
      monensin. Dextran with a molecular weight of 3000 was released from vesicles
      after 8 h of infection, while dextran with a molecular weight of 10,000 was
      mainly retained in vesicles. The results suggest that CPV infection does not
      cause disruption of endosomal vesicles. However, the permeability of endosomal
      membranes apparently changes during CPV infection, probably due to the PLA(2)
      activity of the virus. These results suggest that parvoviral PLA(2) activity is
      essential for productive infection and presumably utilized in membrane
      penetration process of the virus, but CPV also needs other pH-dependent changes
      or factors to be released to the cytoplasm from endocytic vesicles.

PMID- 14644610
TI  - Infection, replication, and cytopathology of human papillomavirus type 31 in
      trophoblasts.
AB  - Human papillomavirus (HPV) DNA is preferentially found in spontaneous abortions,
      specifically residing in trophoblasts, and transfected HPV-16 DNA replicates and
      produces progeny in 3A trophoblasts in culture. In this study 3A trophoblasts
      were shown to display both HPV receptors and infection by HPV-31b and HPV-6 virus
      resulted in de novo (increasing) HPV DNA replication in these cells (inhibited by
      neutralizing anti-HPV31b antibodies). Reverse transcription-polymerase chain
      reaction analysis revealed that E1;E4, E6, and L1 were significantly expressed at
      days 5 (early) and 10 (late), respectively, and in situ immunocytochemistry
      verified L1 protein expression. Perhaps most important, HPV 31b virus infection
      caused both a decrease in 3A trophoblast cell numbers in a dose-dependent manner
      and a low trophoblast-endometrial cell adhesion (both inhibited by neutralizing
      anti-HPV-31 antibodies). These data further support the hypothesis that HPVs are
      fully active in trophoblasts and may cause some spontaneous abortions.

PMID- 14644611
TI  - Delayed viral replication and CD4(+) T cell depletion in the rectosigmoid mucosa
      of macaques during primary rectal SIV infection.
AB  - Rectal infection of macaques by SIV is a model for rectal HIV transmission. We
      focus here on the digestive tract during days 7-14 of primary rectal infection by
      SIV in 15 rhesus macaques. Surprisingly, we did not detect productively infected
      cells in the rectosigmoid colon at early stages of viral dissemination. This
      strongly suggests that there is no massive viral amplification in the
      rectosigmoid colon prior to viral dissemination. As dissemination proceeds,
      productively infected T cells are observed in the rectosigmoid colon and small
      intestine, with rectosigmoid colon showing the heaviest viral load. Lymphoid
      follicles are infected prior to lamina propria at both sites. When viral
      dissemination is widespread, inflammatory infiltrates are visible in the
      rectosigmoid colon, but not in the small intestine. An important decrease in
      CD4(+) T cells is then observed in the lamina propria of the rectosigmoid colon
      only.

PMID- 14644612
TI  - Direct interaction of TFIIB and the IE protein of equine herpesvirus 1 is
      required for maximal trans-activation function.
AB  - Recently, we reported that the immediate-early (IE) protein of equine herpesvirus
      1 (EHV-1) associates with transcription factor TFIIB [J. Virol. 75 (2001),
      10219]. In the current study, the IE protein purified as a glutathione-S
      transferase (GST) fusion protein was shown to interact directly with purified
      TFIIB in GST-pulldown assays. A panel of TFIIB mutants employed in protein
      binding assays revealed that residues 125 to 174 within the first direct repeat
      of TFIIB mediate its interaction with the IE protein. This interaction is
      physiologically relevant as transient transfection assays demonstrated that (1).
      exogenous native TFIIB did not perturb IE protein function, and (2). ectopic
      expression of a TFIIB mutant that lacked the IE protein interactive domain
      significantly diminished the ability of the IE protein to trans-activate EHV-1
      promoters. These results suggest that an interaction of the IE protein with TFIIB
      is an important aspect of the regulatory role of the IE protein in the trans
      activation of EHV-1 promoters.

PMID- 14644613
TI  - Identification of two histidines necessary for reovirus mRNA guanylyltransferase
      activity.
AB  - Grass carp reovirus, a segmented double-stranded RNA virus, is a member of the
      genus aquareovirus in the Reoviridae family. Grass carp reovirus VP1 was shown to
      be an mRNA guanylyltransferase. The enzyme demonstrated maximum activity <or= pH
      6.0. This low pH maximum is conserved among the known guanylyltransferases of the
      Reoviridae family, but is not a property of the KxDG guanylyltransferases. The
      positive effect of low pH was detected for both autoguanylylation and GMP
      transfer, the two steps in the guanylyltransferase reaction. The effect of pH on
      enzymatic activity suggested that histidine protonation is responsible for the
      observed increase in guanylyltransferase activity. Mutagenesis of the two
      histidines conserved among the orthoreovirus and aquareovirus
      guanylyltransferases demonstrated that they are necessary for activity.

PMID- 14644614
TI  - Surface-exposed amino- and carboxy-terminal residues are crucial for the
      initiation of assembly in Pepper vein banding virus: a flexuous rod-shaped virus.
AB  - The mechanism of assembly of flexuous viruses, such as potyviruses, is poorly
      understood. Using a recombinant system, we provide evidence that disassembly and
      reassembly of Pepper vein banding virus (PVBV), a member of the genus potyvirus,
      proceeds via a ring-like intermediate, and show that electrostatic interactions
      may be pivotal in stabilizing the particles. Although the surface-exposed N- and
      C-terminal residues can be removed from the virus-like particles (VLPs) by
      limited trypsinization without affecting their stability, such truncated CP
      subunits are unable to form VLPs. To further evaluate importance of these
      residues, N- and C-terminal deletion mutants were generated and their assembly
      behavior was investigated. N-terminal 53 and C-terminal 23 amino acids were found
      to be crucial for the intersubunit interactions involved in the initiation of
      virus assembly. These segments are surface exposed in the ring-like intermediate
      and dispensable for further interactions that result in the formation of the
      VLPs.

PMID- 14644615
TI  - Vesicular stomatitis virus expressing a chimeric Sindbis glycoprotein containing
      an Fc antibody binding domain targets to Her2/neu overexpressing breast cancer
      cells.
AB  - Vesicular stomatitis virus (VSV) is a candidate for development for cancer
      therapy. It is an oncolytic virus that is safe in humans. Recombinant virus can
      be made directly from plasmid components. We attempted to create a virus that
      targeted specifically to breast cancer cells. Nonreplicating and replicating
      pseudotype VSV were created whose only surface glycoprotein (gp) was a Sindbis
      gp, called Sindbis-ZZ, modified to severely reduce its native binding function
      and to contain the Fc-binding domain of Staphylococcus aureus protein A. When
      titered on Her2/neu overexpressing SKBR3 human breast cancer cells, pseudotype
      VSV coated with Sindbis-ZZ had <1% the titer of pseudotype VSV coated with wild
      type Sindbis gp. Titer was increased 50-fold when the Sindbis-ZZ pseudotype was
      conjugated with 4D5, a mouse monoclonal antibody directed against the Her2/neu
      receptor. Titers of antibody-conjugated virus were increased 36-fold on a second
      human breast cancer cell line, MCF7/H2, which expressed lower concentrations of
      Her2/neu receptor on the cell surface. At multiple concentrations of antibody,
      titers on SKBR3 cells were significantly greater when the virus was incubated
      with Herceptin, an antibody with a human Fc, than with 4D5, a mouse antibody,
      reflecting the known higher affinity of the protein A Fc-binding domain for human
      Fc. Analysis of the protein composition of the pseudotype VSV found low
      expression of the modified Sindbis gp on the virus accounting, in part, for a
      viral titer that did not exceed 1.2 x 10(5)/ml. This work demonstrates the
      ability to easily create, directly from plasmid components, an oncolytic
      replicating VSV with a restricted host cell range.

PMID- 14644616
TI  - Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine
      receptors and rat brain acetylcholinesterase.
AB  - Effects of commonly used carbamate pesticides on rat neuronal nicotinic
      acetylcholine receptors expressed in Xenopus laevis oocytes have been
      investigated using the two-electrode voltage clamp technique. The potencies of
      these effects have been compared to the potencies of the carbamates to inhibit
      rat brain acetylcholinesterase. The potency order of six carbamates to inhibit
      alpha4beta4 nicotinic receptors is fenoxycarb > EPTC > carbaryl, bendiocarb >
      propoxur > aldicarb with IC50 values ranging from 3 microM for fenoxycarb to 165
      microM for propoxur and >1 mM for aldicarb. Conversely, the potency order of
      these carbamates to inhibit rat brain acetylcholinesterase is bendiocarb >
      propoxur, aldicarb > carbaryl > EPTC, fenoxycarb with IC50 values ranging from 1
      microM for bendiocarb to 17 microM for carbaryl and > mM for EPTC and fenoxycarb.
      The alpha4beta2, alpha3beta4, and alpha3beta2 nicotinic acetylcholine receptors
      are inhibited by fenoxycarb, EPTC, and carbaryl with potency orders similar to
      that for alpha4beta4 receptors. Comparing the potencies of inhibition of the
      distinct subtypes of nicotinic acetylcholine receptors shows that the alpha3beta2
      receptor is less sensitive to inhibition by fenoxycarb and EPTC. The potency of
      inhibition depends on the carbamate as well as on a combination of alpha and beta
      subunit properties. It is concluded that carbamate pesticides affect different
      subtypes of neuronal nicotinic receptors independently of acetylcholinesterase
      inhibition. This implicates that neuronal nicotinic receptors are additional
      targets for some carbamate pesticides and that these receptors may contribute to
      carbamate pesticide toxicology, especially after long-term exposure.

PMID- 14644617
TI  - Sex differences in the toxicokinetics of inhaled solvent vaporsin humans 1. m
      Xylene.
AB  - The aim of this study was to evaluate possible sex differences in the inhalation
      toxicokinetics of m-xylene vapor. Seventeen healthy volunteers (nine women and
      eight men) were exposed to m-xylene (200 mg/m3) and to clean air (control
      exposure) on different occasions during 2 h of light physical exercise (50 W).
      The chosen level corresponds to the occupational exposure limit (8-h time
      weighted average) in Sweden. m-Xylene was monitored up to 24 h after exposure in
      exhaled air, blood, saliva, and urine by headspace gas chromatography. m
      Methylhippuric acid (a metabolite of m-xylene) was analyzed in urine by high
      performance liquid chromatography. Body fat and lean body mass (LBM) were
      estimated from sex-specific equations using bioelectrical impedance, body weight,
      height, and age. Genotypes and/or phenotypes of cytochromes P450 2E1 and 1A1,
      glutathione transferases M1 and P1, and epoxide hydrolase were determined. The
      toxicokinetic profile in blood was analyzed using a two-compartment population
      model. The area under the concentration-time curve (AUC) of m-xylene in exhaled
      air postexposure was larger in women than in men. In addition, the excretion via
      exhaled air was significantly higher in women when correcting for body weight or
      LBM. In contrast, the men had a significantly higher volume of distribution,
      excretion of m-methylhippuric acid in urine, and AUC of m-xylene in urine. The
      toxicokinetic analyses revealed no differences between subjects of different
      metabolic genotypes or phenotypes. In conclusion, the study indicates small sex
      differences in the inhalation toxicokinetics of m-xylene, which can be explained
      by body build.

PMID- 14644618
TI  - Sex differences in the toxicokinetics of inhaled solvent vapors in humans 2. 2
      propanol.
AB  - The aim of this study was to evaluate possible sex differences in the inhalation
      toxicokinetics of 2-propanol vapor. Nine women and eight men were exposed on
      different occasions for 2 h during light physical exercise (50 W) to 2-propanol
      (350 mg/m3) and to clean air (control exposure). The level corresponds to the
      Swedish occupational exposure limit. 2-Propanol and its metabolite acetone were
      monitored up to 24 h after exposure in exhaled air, blood, saliva, and urine by
      headspace gas chromatography. Body fat and lean body mass were estimated from sex
      specific equations using bioelectrical impedance, body weight, height, and age.
      Genotypes were determined by PCR-based assays for alcohol dehydrogenase and
      cytochrome P450 2E1 (CYP2E1). The CYP2E1 phenotype was assessed by the 2-h plasma
      6-hydroxychlorzoxazone/chlorzoxazone metabolic ratio in vivo. The toxicokinetic
      profile in blood was analyzed using a one-compartment population model. The
      following sex differences were significant at the p = 0.05 level (Student's t
      test). The respiratory uptake was lower and the volume of distribution smaller in
      females. The women had a slightly shorter half-time of 2-propanol in blood and a
      higher apparent total clearance when corrected for body composition. However,
      women reached approximately four times higher 2-propanol levels in exhaled air at
      10-min postexposure and onward. Acetone in blood was markedly higher in females
      than in males in the control experiment and slightly higher following exposure to
      2-propanol. A marked sex difference was that of a 10-fold higher in vivo
      blood:breath ratio in men, suggesting sex differences in the lung metabolism of 2
      propanol. The most marked sex difference was that of salivary acetone, for which
      an approximately 100-fold increase was seen in women, but no increase in men,
      after exposure to 2-propanol compared to clean air. The toxicokinetic analysis
      revealed no significant differences in toxicokinetics between subjects of
      different metabolic genotypes or phenotypes. In conclusion, the study indicates
      several sex differences in the inhalation toxicokinetics of 2-propanol. Most of
      these differences are consistent with anatomical differences between women and
      men. However, body build can not explain the sex differences in 2-propanol levels
      in expired air and acetone in saliva.

PMID- 14644619
TI  - Teratogenicity by the hERG potassium channel blocking drug almokalant: use of
      hypoxia marker gives evidence for a hypoxia-related mechanism mediated via
      embryonic arrhythmia.
AB  - The rapid component of the delayed rectifying potassium ion current (IKr), plays
      an important role in cardiac repolarization. In rats, potent IKr channel blocking
      drugs cause similar stage-specific malformations (such as orofacial clefts and
      digital reductions) on gestational days (GDs) 10-14 as after periods of embryonic
      oxygen deprivation (hypoxia). The idea of a hypoxia-related teratogenic mechanism
      is supported by studies using rat embryos cultured in vitro. These studies show
      that the embryonic heart reacts with concentration-dependent bradycardia,
      arrhythmia, and cardiac arrest when exposed to IKr blockers on GDs 10-14. The
      main purpose of this study was to investigate whether previously shown
      teratogenic doses on GD 11 and 13 of the selective IKr blocker almokalant (ALM)
      induce hypoxia in rat embryos in vivo by using the hypoxia marker pimonidazole
      hydrochloride (PIM). Rats were orally dosed with almokalant or tap water on GD 11
      (150 micromol/kg), 13 (50 micromol/kg), or 16 (800 micromol/kg), followed by PIM
      intravenously 30 min later. Two hours after the PIM dose, the embryonic heart
      activity was videotaped and analysed, and the embryos were fixed, sectioned, and
      immunostained. Computer-assisted image analysis showed a two- and threefold
      increase in hypoxia staining in embryos exposed to teratogenic doses of ALM on
      GDs 11 and 13. Embryonic arrhythmia was observed in almokalant groups on these
      GDs, but not in controls. In contrast, dosing on GD 16, with a much higher dose
      (800 micromol/kg), caused neither hypoxia nor any effects on heart rhythm. The
      results support the IKr-related arrhythmia-hypoxia hypothesis, by showing that
      the potent IKr-blocking drug, almokalant, (1) causes severe embryonic hypoxia and
      arrhythmia at stages (GDs 11 and 13) when developmental toxicity could be induced
      and IKr is functional and (2) does not cause hypoxia or affect heart rhythm at a
      developmental stage when IKr is suppressed (GD 16) and potent IKr blockers do not
      induce developmental toxicity.

PMID- 14644620
TI  - Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with
      elevated angiotensin II, endothelin-1, and mean arterial blood pressure.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates toxicity of xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p
      dioxin. Genetic deletion of the AhR leads to cardiac hypertrophy, suggesting a
      role for the AhR in cardiovascular physiology and disease; however, the pathways
      involved in the development of cardiac hypertrophy have not been determined.
      Thus, we investigated the role of (1) pressure overload using indwelling
      catheters and (2) vasoactive peptides endothelin-1 (ET-1) and angiotensin II (Ang
      II), assessed by RIA, in the progression of cardiac hypertrophy in AhR-null mice.
      Histochemical analysis, expression of cardiac hypertrophy marker genes, and
      echocardiography were used to assess the degree of cardiac hypertrophy. AhR-null
      mice developed elevated mean arterial pressures (MAP) by 5 months, which was
      associated with a two- and ninefold increase in plasma ET-1 and Ang II,
      respectively, compared to wild-type. Captopril-treatment (4 mg/kg) of AhR-null
      mice from 2 to 5 months of age significantly decreased MAP and plasma Ang II, but
      did not affect ET-1. Further, captopril improved cardiac function and reduced
      cardiac hypertrophy as evidenced by reduction in left ventricle mass, left
      ventricle internal dimension, and molecular cardiac hypertrophy markers.
      Captopril also decreased fibrosis of the heart and kidney. These findings show
      that pressure overload is associated with elevated ET-1 and hypertrophic growth
      of the heart and that cardiac hypertrophy is mediated, in part, by Ang II.

PMID- 14644621
TI  - Transcriptional and posttranscriptional roles for p38 mitogen-activated protein
      kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin).
AB  - Deoxynivalenol (DON, vomitoxin) is a trichothecene mycotoxin that potentially
      mediates toxicity by upregulating proinflammatory cytokine gene expression in
      vitro and in vivo. The purpose of this study was to test the hypothesis that DON
      induced activation of mitogen-activated protein kinases (MAPKs) mediates
      transcriptional and posttranscriptional upregulation of TNF-alpha gene
      expression. RNAse protection assay revealed that DON at 100 to 500 ng/ml induced
      mRNA expression of TNF-alpha as well as IL-6, IFN-gamma, TGFbeta-1, and TGFbeta-3
      and that these effects were potentiated by 100 ng/ml lipopolysaccharide (LPS).
      DON was found to induce phosphorylation of p38 kinase, extracellular signal
      regulated kinases (ERKs), and c-Jun amino terminal kinases (JNKs) in a dose
      dependent manner in the RAW 264.7 murine macrophage model. A luciferase reporter
      gene driven by the murine TNF-alpha promoter was used to assess the role of
      various MAPKs on DON upregulation of TNF-alpha gene transcription. The p38
      inhibitor SB203580 reduced induction of luciferase activity by DON, LPS, and DON
      + LPS. In addition, the ERK inhibitor PD 98059 blocked DON- and DON + LPS-induced
      luciferase activity whereas the JNK inhibitor impaired LPS- and DON + LPS-induced
      luciferase activity. To study the effects of MAPKs on DON-induced TNF-alpha mRNA
      stability, an asynchronous model was used whereby cells were pretreated with LPS
      for 4 h and the medium was removed. Following incubation with medium containing a
      transcription inhibitor, 5,6-dichloro-beta-D-ribofuranosyl-benzimidazole, MAPK
      inhibitors and/or DON (250 ng/ml) cultures were monitored for TNF-alpha mRNA
      expression. DON-induced TNF-alpha mRNA stabilization was abrogated in the
      presence of SB 203580, whereas the stabilization by DON was not affected by PD
      98059 or SP 600125. To verify the role of MAPKs in DON + LPS-induced TNF-alpha
      production, cells were incubated with LPS, DON, or LPS + DON for 18 h in the
      presence of inhibitors. ELISA of supernatant indicated that induction of TNF
      alpha production by DON alone was significantly reduced by SB 203580 and PD
      98059, whereas all three inhibitors blocked LPS- and DON + LPS-induced TNF-alpha
      production. Taken together, these results suggest that relative to DON-induced
      TNF-alpha mRNA expression, p38 and ERK activation contribute to DON-induced
      transcriptional upregulation whereas p38 plays a role in increasing mRNA
      stability.

PMID- 14644622
TI  - Nickel (Ni2+) enhancement of microtubule assembly in vitro is dependent on GTP
      function.
AB  - Microtubule (MT) assembly in vitro is accompanied by hydrolysis of tubulin-bound
      GTP at E-site. Ni2+, a human carcinogen, has been shown to markedly perturb the
      MT system in cultured cells and enhance MT assembly in vitro. To further probe
      the mechanisms of such multiple Ni2+ damaging actions on MT, we have focused on
      dissecting the role of the Ni2+/GTP interaction in influencing MT assembly in
      vitro as monitored by a turbidity assay at A350 at 27 degrees C using purified
      bovine brain MT proteins containing 162 microM each of Mg2+ and EGTA. MT assembly
      was initiated by addition of GTP and progressed in a GTP dose-dependent manner.
      The minimal and optimal exogenous [GTP] required for MT assembly were 15.6 and
      500 microM, respectively. Replacement of GTP (25-87%) with increasing [NiCl2]
      while keeping the sum of [GTP] and [Ni2+] constant at 500 microM enabled MT
      assembly to proceed with shortened "lags" but reaching the same maximum plateau
      levels or elongation rates as with 500 microM GTP only. However, in reactions
      with Ni2+ replacing >94% of GTP, marked inhibition of MT assembly (lower
      plateaus) occurred. Electron microscopic (EM) examinations showed that MT formed
      with high Ni2+ substitutions for GTP appeared shorter, more numerous, and
      resistant to Ca2+ disruption than those assembled with 500 microM GTP only.
      Notably, in the presence of 500 microM Ni2+ with no GTP added, no typical MT were
      observed under EM, despite increases in turbidity of the reaction. In addition,
      the critical concentration of MT proteins required for assembly was also
      considerably decreased under conditions of Ni2+ replacements of GTP. These
      results point to an important role of GTP/Ni2+ interaction in modulating the Ni2+
      enhancement of MT assembly in vitro.

PMID- 14644623
TI  - Effects of gallium on immune stimulation and apoptosis induction in human
      peripheral blood mononuclear cells.
AB  - Gallium is commonly used in the semiconductor industry and medical field.
      Biologically, gallium is able to interrupt iron metabolism. Exposure to gallium
      has been shown to affect the human immune system. The purpose of this study was
      to investigate the in vitro biological effects of different gallium
      concentrations on cultured human peripheral blood mononuclear cells (PBMCs) in
      terms of cell growth, cytokine release, and apoptosis induction. In addition, the
      in vivo effects of gallium were analyzed by Wistar rat model. Our results
      revealed that low concentrations (1-10 microg/ml) of gallium promoted cells to
      enter the S phase of cell cycle and enhanced cellular release of tumor necrosis
      factor-alpha, interleukin-1beta, and interferon-gamma, both in vitro and in vivo.
      In contrast, high concentrations of gallium (50-100 microg/ml) induced apoptosis.
      Furthermore, gallium-induced cytokine release and apoptosis could be inhibited by
      iron-saturated transferrin (Tf-Fe). These results suggest that the concentration
      dependent effects of gallium on PBMCs are related to iron metabolism.

PMID- 14644624
TI  - Role of tumor necrosis factor receptor 1 (p55) in hepatocyte proliferation during
      acetaminophen-induced toxicity in mice.
AB  - Hepatocyte proliferation represents an important part of tissue repair. In these
      studies, TNF receptor 1 (TNFR1) knockout mice were used to analyze the role of
      TNF-alpha in hepatocyte proliferation during acetaminophen-induced
      hepatotoxicity. Treatment of wild-type (WT) mice with acetaminophen (300 mg/kg)
      resulted in centrilobular hepatic necrosis. This was associated with
      proliferation of hepatocytes surrounding the damaged areas, which was evident at
      24 h. The cell cycle regulatory proteins, cyclin D1 and cyclin A, were also up
      regulated in hepatocytes. In contrast, in TNFR1-/- mice, which exhibit
      exaggerated acetaminophen hepatotoxicity, hepatocyte proliferation, and
      expression of cyclin D1 and cyclin A, as well as the cyclin dependent kinases,
      Cdk4 and Cdk2, were reduced. The cyclin-dependent kinase inhibitor p21 was also
      induced in the liver following acetaminophen administration. This was greater in
      TNFR1-/- mice compared to WT mice. To investigate mechanisms mediating the
      reduced hepatic proliferative response of TNFR1-/- mice, we analyzed phosphatidyl
      inositol-3-kinase (PI-3K) signaling. In both WT and TNFR1-/- mice, acetaminophen
      caused a rapid increase in total PI-3K within 3 h. Acetaminophen also increased
      phosphorylated PI-3K, but this was delayed 6-12 h in TNFR1-/- mice. Expression of
      Akt, a downstream target of PI-3K, was increased in both WT and TNFR1-/- mice in
      response to acetaminophen. However, the increase was greater in WT mice.
      Acetaminophen-induced expression of phosphorylated STAT3, a key regulator of
      cytokine-induced hepatocyte proliferation, was also delayed in TNFR1-/- mice
      relative to WT. These data suggest that TNF-alpha signaling through TNFR1 is
      important in regulating hepatocyte proliferation following acetaminophen-induced
      tissue injury. Delayed cytokine signaling may account for reduced hepatocyte
      proliferation and contribute to exaggerated acetaminophen-induced hepatotoxicity
      in TNFR1-/- mice.

PMID- 14644625
TI  - Sulfur mustard induces the formation of keratin aggregates in human epidermal
      keratinocytes.
AB  - The vesicant sulfur mustard is an alkylating agent that has the capacity to cross
      link biological molecules. We are interested in identifying specific proteins
      that are altered upon sulfur mustard exposure. Keratins are particularly
      important for the structural integrity of skin, and several genetically inherited
      blistering diseases have been linked to mutations in keratin 5 and keratin 14. We
      examined whether sulfur mustard exposure alters keratin biochemistry in cultured
      human epidermal keratinocytes. Western blotting with specific monoclonal
      antibodies revealed the formation of stable high-molecular-weight "aggregates"
      containing keratin 14 and/or keratin 5. These aggregates begin to form within 15
      min after sulfur mustard exposure. These aggregates display a complex gel
      electrophoresis pattern between approximately 100 and approximately 200 kDa.
      Purification and analysis of these aggregates by one- and two-dimensional gel
      electrophoresis and mass spectrometry confirmed the presence of keratin 14 and
      keratin 5 and indicate that at least some of the aggregates are composed of
      keratin 14-keratin 14, keratin 14-keratin 5, or keratin 5-keratin 5 dimers. These
      studies demonstrate that sulfur mustard induces keratin aggregation in
      keratinocytes and support further investigation into the role of keratin
      aggregation in sulfur mustard-induced vesication.

PMID- 14644626
TI  - Body weight considerations in the B6C3F1 mouse and the use of dietary control to
      standardize background tumor incidence in chronic bioassays.
AB  - In B6C3F1 mice, the rate of body growth influences susceptibility to liver
      neoplasia and large variations in body weight can complicate the interpretation
      of bioassay data. The relationship between body weight and liver tumor incidence
      was calculated for historical control populations of male and female ad libitum
      fed mice (approx. 2,750 and 2,300 animals, respectively) and in populations of
      male and female mice which had been subjected to forced body weight reduction due
      to either dietary restriction or exposure to noncarcinogenic chemicals (approx.
      1,600 and 1,700, respectively). Resulting tumor risk data were then used to
      construct idealized weight curves for male and female B6C3F1 mice; these curves
      predict a terminal background liver tumor incidence of 15-20%. Use of dietary
      control to manipulate body growth of male B6C3F1 mice to fit the idealized weight
      curve was evaluated in a 2-year bioassay of chloral hydrate. Cohorts of mice were
      successfully maintained at weights approximating their idealized target weights
      throughout the study. These mice exhibited less body weight variation than their
      ad libitum-fed counterparts (e.g., standard deviations of body weight were 1.4
      and 3.4 g for respective control groups at 36 weeks). Historical control body
      weight and tumor risk data from the two male mouse populations were utilized to
      predict background liver tumor rates for each experimental group of the chloral
      hydrate study. The predicted background tumor rates closely matched the observed
      rates for both the dietary controlled and ad libitum-fed chloral hydrate control
      groups when each mouse was evaluated according to either its weekly food
      consumption or its weekly change in body weight.

PMID- 14644627
TI  - Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice.
AB  - Chloral hydrate, which is used as a sedative in pediatric medicine and is a by
      product of water chlorination, is hepatocarcinogenic in B6C3F1 mice, a strain
      that can exhibit high rates of background liver tumor incidence, which are
      associated with increased body weight. In this study, dietary control was used to
      manipulate body growth in male B6C3F1 mice in a 2-year bioassay of chloral
      hydrate. Male B6C3F1 mice were treated with water or 25, 50, or 100 mg/kg chloral
      hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled
      mice. The latter received variably restricted feed allocations to maintain their
      body weights on a predetermined "idealized" weight curve predictive of a terminal
      background liver tumor incidence of 15-20%. These mice exhibited less individual
      body weight variation than did their ad libitum-fed counterparts. This was
      associated with a decreased variation in liver to body weight ratios, which
      allowed the demonstration of a statistically significant dose response to chloral
      hydrate in the dietary controlled, but not the ad libitum-fed, test groups.
      Chloral hydrate increased terminally adjusted liver tumor incidence in both
      dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups,
      respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a
      statistically significant dose response was observed only in the dietary
      controlled mice. This dose response positively correlated with markers of
      peroxisomal proliferation in the dietary controlled mice only. The study suggests
      that dietary control not only improves terminal survival and decreases interassay
      variation, but also can increase assay sensitivity by decreasing intra-assay
      variation.

PMID- 14644628
TI  - Toxicokinetics of chloral hydrate in ad libitum-fed, dietary-controlled, and
      calorically restricted male B6C3F1 mice following short-term exposure.
AB  - Chloral hydrate is widely used as a sedative in pediatric medicine and is a by
      product of water chlorination and a metabolic intermediate in the
      biotransformation of trichloroethylene. Chloral hydrate and its major metabolite,
      trichloroacetic acid, induce liver tumors in B6C3F1 mice, a strain that can
      exhibit high rates of background liver tumor incidence, which is associated with
      increased body weight. This report describes the influence of diet and body
      weight on the acute toxicity, hepatic enzyme response, and toxickinetics of
      chloral hydrate as part of a larger study investigating the carcinogenicity of
      chloral hydrate in ad libitum-fed and dietary controlled mice. Dietary control
      involves moderate food restriction to maintain the test animals at an idealized
      body weight. Mice were dosed with chloral hydrate at 0, 50, 100, 250, 500, and
      1000 mg/kg daily, 5 days/week, by aqueous gavage for 2 weekly dosing cycles.
      Three diet groups were used: ad libitum, dietary control, and 40% caloric
      restriction. Both dietary control and caloric restriction slightly reduced acute
      toxicity of high doses of chloral hydrate and potentiated the induction of
      hepatic enzymes associated with peroxisome proliferation. Chloral hydrate
      toxicokinetics were investigated using blood samples obtained by sequential tail
      clipping and a microscale gas chromatography technique. It was rapidly cleared
      from serum within 3 h of dosing. Trichloroacetate was the major metabolite in
      serum in all three diet groups. Although the area under the curve values for
      serum trichloroacetate were slightly greater in the dietary controlled and
      calorically restricted groups than in the ad libitum-fed groups, this increase
      did not appear to completely account for the potentiation of hepatic enzyme
      induction by dietary restriction.

PMID- 14644629
TI  - Differential metabolism of acrylonitrile to cyanide is responsible for the
      greater sensitivity of male vs female mice: role of CYP2E1 and epoxide
      hydrolases.
AB  - Acrylonitrile (AN) is a potent toxicant and a known rodent carcinogen. AN
      epoxidation to cyanoethylene oxide (CEO) via CYP2E1 and its subsequent metabolism
      via epoxide hydrolases (EH) to yield cyanide is thought to be responsible for the
      acute toxicity and mortality of AN. Recent reports showed that male mice are more
      sensitive than females to the acute toxicity/mortality of AN. The present work
      was undertaken to assess the metabolic and enzymatic basis for the greater
      sensitivity of male vs female mice to AN toxicity. Male and female wild-type and
      CYP2E1-null mice received AN at 0, 2.5, 10, 20, or 40 mg/kg by gavage. Cyanide
      concentrations were measured at 1 or 3 h after dosing. Current data demonstrated
      that cyanide levels in blood and tissues of AN-treated wild-type mice of both
      sexes were significantly greater than in vehicle-treated controls and increased
      in a dose-dependent manner. In contrast, cyanide levels in AN-treated CYP2E1-null
      mice were not statistically different from those measured in vehicle-treated
      controls. Furthermore, higher levels of cyanide were detected in male wild-type
      mice vs females in association with greater sensitivity of males to the acute
      toxicity/mortality of this chemical. Using Western blot analysis, negligible
      difference in CYP2E1 expression with higher levels of soluble and microsomal EH
      (sEH and mEH) was detected in the liver of male vs female mice. In kidneys, male
      mice exhibited higher expression of both renal CYP2E1 and sEH than did female
      mice. In conclusion, higher blood and tissue cyanide levels are responsible for
      the greater sensitivity of male vs female mice to AN. Further, higher expression
      of CYP2E1 and EH in male mice may contribute to greater formation of CEO and its
      subsequent metabolism to yield cyanide, respectively.

PMID- 14644630
TI  - Toluene exposure increases aminophylline-induced seizure susceptibility in mice.
AB  - The effects of toluene on the sensitivity to seizures induced by aminophylline
      were investigated. Mice were pretreated with an ip injection of corn oil or
      toluene (100-500 mg/kg) followed by a timed intravenous infusion of aminophylline
      at various time intervals to assess the seizure thresholds and lethal doses.
      Toluene increased seizure susceptibility to aminophylline in a dose- and time
      dependent manner. Toluene-induced enhancement of seizure susceptibility to
      aminophylline occurred as early as 30 min and persisted for at least 3 days after
      a single administration of toluene (500 mg/kg). Treatment of benzaldehyde, one of
      toluene's metabolites, also showed an increase in the susceptibility to
      aminophylline. The enhancing effect was also observed in caffeine-induced
      seizures 1 h, but not 1 day after toluene treatment. These results suggest that
      individuals with toluene exposure may increase the risk for convulsive and even
      lethal complications associated with the therapeutic use of aminophylline.

PMID- 14644631
TI  - Brain mast cells are influenced by chemosensory cues associated with estrus
      induction in female prairie voles (Microtus ochrogaster).
AB  - Historically, the brain has been viewed as protected from the infiltration of
      peripheral hematopoietic cells by the blood-brain barrier. However, numerous
      immune cell types have been found in the central nervous system (CNS). Mast
      cells, granulocytic immune cells, are found in the CNS of birds and mammals and
      their numbers and location are influenced by both extrinsic and intrinsic
      factors, including reproductive behavior and endocrine status. The present study
      used female prairie voles (Microtus ochrogaster) to investigate the interactions
      between brain mast cells and stimuli associated with estrus induction. Unlike
      spontaneous ovulators such as rats and mice, female prairie voles are induced
      into estrus by chemosensory stimuli present in conspecific male urine. Prior to
      estrus induction, female voles have undetectable concentrations of estrogen that
      rise rapidly following exposure to a male or male urine. In the first experiment,
      we examined whether mast cells may be influenced by estrus induction. Female
      voles exposed to conspecific male urine had increased numbers of mast cells in
      the main olfactory bulbs and epithalamus (medial habenula), but not the thalamus
      or median eminence, relative to control groups. Next, to determine if this mast
      cell increase was the result of elevated estrogen concentrations, female voles
      were injected with estradiol or vehicle and brain mast cell numbers analyzed. No
      differences in brain mast cell numbers were observed between estradiol-injected
      and control females in any brain area investigated. Together, these results lend
      further support to the contention that mast cell numbers and/or distribution can
      be influenced by reproductively relevant stimuli and underscore the utility of
      this vole model for delineating the function of brain mast cells.

PMID- 14644632
TI  - Effects of dispersal status on pituitary and gonadal function in the male spotted
      hyena.
AB  - Male spotted hyenas (Crocuta crocuta) reach puberty at 24 months of age and then
      usually emigrate from their natal clans one to 52 months later. Recent work has
      shown that reproductive success is very low among adult males still residing in
      their natal groups, and it is similarly low among recent or "short-term"
      immigrants. Long-term immigrants father the vast majority of cubs born. Here we
      inquired whether these differences in reproductive success might be associated
      with variation among males in pituitary or gonadal function. In one free-living
      hyena population in Kenya, we compared baseline levels of plasma luteinizing
      hormone (LH) and testosterone (T) among adult natal males, short-term immigrants,
      and long-term immigrants, and we also compared their pituitary and gonadal
      responses to GnRH challenge. Mean basal plasma LH values did not differ among
      groups, but mean basal T concentrations in long-term immigrants were higher than
      those in either natal males or short-term immigrants. Similarly, pituitary
      response to GnRH challenge did not vary significantly among groups, but
      testicular response to challenge was greater in long-term immigrants than in
      natal males or short-term immigrants. Thus adult natal and immigrant males
      exhibited similar pituitary function but testicular function was attenuated among
      adult males that had not yet left their natal groups and also among males
      attempting to become established in new social groups. This suggests that, like
      the act of emigration itself, the process of social integration during
      immigration may have important physiological consequences for male mammals
      transferring between groups.

PMID- 14644633
TI  - Psychological effects of subthreshold exposure to the putative human pheromone
      4,16-androstadien-3-one.
AB  - Research on human putative pheromones has recently focused on the effects of
      exposure to 4,16-androstadien-3-one (androstadienone). This steroid has been
      observed in the skin, axillary hair, and blood plasma, primarily in males. In
      addition to effects of the steroid on measures of physiological arousal and brain
      blood flow, positive mood effects have also been reported. The current study
      further investigated mood effects of androstadienone exposure (250 microM) in
      women in two experiments. Through psychophysical testing of each individual we
      controlled for whether any observed mood effects could be related to sensory
      detection of the steroid. In both experiments, we observed positive changes of
      women's feeling of being focused, which could not be related to sensory detection
      of the steroid. Overall, the patterns of results were significantly correlated
      between the two experiments. In conclusion, this study corroborates earlier
      findings suggesting that androstadienone exposure yields effects on women's mood;
      the feeling of being focused. The mood effects were not dependent on menstrual
      cycle phase. Further, these effects are replicable and occur also when
      androstadienone detection is rigorously controlled for across variation in
      menstrual cycle.

PMID- 14644634
TI  - Testosterone decreases the potential for song plasticity in adult male zebra
      finches.
AB  - Zebra finches are age-limited learners; males crystallize their songs at 90 days
      and do not subsequently alter those songs. However, a variety of interventions,
      including deafening and syringeal denervation, result in long-term changes to the
      crystallized song. These changes can be prevented by lesioning nucleus LMAN. As
      different social contexts for song production result in differential activation
      of LMAN, we asked whether the social context experienced by adult males would
      affect their ability to alter their songs in response to syringeal denervation.
      Males able to see and direct their songs to females made fewer changes to their
      songs than did males that could hear but not see females, but this trend was not
      significant. The volume of a male's HVc, a forebrain song control nucleus, also
      failed to predict the degree to which a male would change his song. However,
      testis mass was significantly correlated with the number of changes made to the
      song, indicating that variations in testosterone modulate adult song plasticity.
      We directly tested the effect of circulating testosterone on adult song
      plasticity by implanting adult males with either testosterone or flutamide, a
      testosterone receptor blocker, and tracking song changes triggered by ts nerve
      injury. As predicted, males implanted with testosterone changed their songs less
      than did males that received flutamide implants. These results suggest that the
      high testosterone concentrations associated with sexual maturity and song
      crystallization in zebra finches continue to act in adult males to reduce the
      potential for vocal plasticity.

PMID- 14644635
TI  - Vasotocin treatment inhibits courtship in male zebra finches; concomitant
      androgen treatment inhibits this effect.
AB  - Zebra finches evolved in arid areas of Australia. Their reproduction is
      stimulated by water availability, which is unpredictable. Cheng (Poult. Sci. Rev.
      5 (1993) 37) hypothesized that the primary mechanism controlling reproduction in
      species relying on unpredictable cues should be inhibitory. The onset of
      stimulatory environmental conditions terminates the inhibition, allowing rapid
      initiation of reproduction. As the primary hormone regulating water balance in
      birds, arginine vasotocin (AVT) appears a likely candidate to modulate
      reproduction in finches. Drought conditions cause sustained AVT release, which in
      other species inhibits androgen production. To determine whether increased AVT
      inhibits reproductive behavior, intact males were tested with females and divided
      into three groups matched for courtship behavior. Osmotic minipumps containing
      (a) saline, (b) 264 ng AVT, or (c) 1320 ng AVT in saline were implanted
      subcutaneously and males tested 48 h later. AVT-treated males socialized with
      females, but the high dose significantly reduced singing and courtship displays.
      To determine whether AVT acted by depressing androgen secretion, additional males
      were given subcutaneous androgen implants and divided into two groups matched for
      courtship behavior. Males were then implanted with minipumps containing (a)
      saline or (b) the high AVT dose. Males treated with AVT plus androgen showed no
      deficits in courtship behavior. These data suggest that AVT secretion during
      periods of drought may inhibit reproduction by inhibiting androgen production.
      Inhibition of reproductive behavior by AVT may be a more general phenomenon.
      Large quantities of AVT or, in mammals the closely-related peptide vasopressin
      (VP), are released when animals are stressed, and high levels of AVT/VP may
      inhibit reproductive behavior. The extremely short half-life of these peptides
      means that once proximal factors become more favorable, the gonads should rapidly
      be released from the peptides' inhibitory actions.

PMID- 14644636
TI  - Effects of testosterone metabolites on copulation and medial preoptic dopamine
      release in castrated male rats.
AB  - The medial preoptic area (MPOA) is an important integrative site for male sexual
      behavior. Dopamine (DA) is released in the MPOA of male rats shortly before and
      during copulation. The recent presence of testosterone (T) may be necessary for
      this precopulatory increase in release. Previously, the postcastration loss of
      copulatory ability mirrored the loss of the DA response to an estrous female, and
      the restoration of copulation with exogenous T was concurrent with the
      reemergence of this DA response. The present study investigated the effectiveness
      of the two major metabolites of T in maintaining copulation and basal and female
      stimulated DA levels. Adult male rats were castrated and received daily
      injections of estradiol benzoate (EB), dihydrotestosterone benzoate (DHTB), EB +
      DHTB, testosterone propionate (TP), or oil vehicle for 3 weeks. Microdialysis
      samples were collected from the MPOA during baseline conditions, exposure to an
      estrous female behind a barrier, and copulation testing. EB + DHTB- and TP
      treated animals had normal basal DA levels and showed a precopulatory DA
      response, and most copulated normally. EB-treated castrates had high basal DA
      levels, but failed to show a female-stimulated increase; most intromitted, but
      none ejaculated. DHTB- and oil-treated groups had low basal levels of
      extracellular DA that did not increase during copulation testing; most failed to
      mount and none ejaculated. These results suggest that E maintains normal basal
      levels of extracellular DA in the MPOA, which are sufficient for suboptimal
      copulation, but that androgen is required for the female-stimulated increase in
      DA release and for facilitation of ejaculation.

PMID- 14644637
TI  - Lack of functional estrogen receptor beta gene disrupts pubertal male sexual
      behavior.
AB  - The estrogen receptor-beta (ERbeta) mediates estrogen action in the female
      gonads, reproductive tract, and central nervous system. In addition, in rats and
      mice, gonadotropin-releasing hormone (GnRH-I) neurons coexpress ERbeta. Here we
      asked if ERbeta plays a role in the onset of puberty and in hypothalamic
      pituitary-gonadal (HPG) axis function in male mice. We examined mating behavior,
      testosterone concentrations, steroid negative feedback on gonadotropins, and GnRH
      I function in male ERbeta knockout (ERbetaKO) and wild-type (WT) mice.
      Peripubertal ERbetaKO males displayed their first ejaculation at a significantly
      older age than WT littermates. Castrated, adult ERbetaKO mice had significantly
      higher plasma luteinizing hormone (LH) than WT counterparts. Estradiol (E2)
      treatment reduced LH and follicle stimulating hormone (FSH) concentrations to an
      equivalent degree in castrates of both genotypes. In three different measures of
      the adult GnRH-I system, no genotypic differences were observed. These data show
      that ERbeta plays an important role in the timing of male sexual behavior at
      puberty, but does not appear to be involved in adult HPG axis functioning.
      Furthermore, our data suggest that a primary role of ERbeta may be to regulate
      ejaculatory behavior.

PMID- 14644638
TI  - Testosterone and prolactin in two songbirds that differ in paternal care: the
      Blue-headed Vireo and the Red-eyed Vireo.
AB  - We investigated the hypothesis that species differences in paternal care in birds
      may result from differences in concentrations of circulating testosterone (T) and
      prolactin (PRL). Concentrations of plasma T and PRL were compared in breeding
      Blue-headed Vireos (Vireo solitarius) and Red-eyed Vireos (Vireo olivaceus),
      passerine congeners with biparental and maternal incubation, respectively. In
      male Blue-headed Vireos, plasma T remained low from prenesting to fledgling
      stages; whereas in male Red-eyed Vireos, plasma T was highest during prenesting
      and progressively decreased during incubation, nestling, and fledgling stages. In
      male Blue-headed Vireos, plasma PRL was similar to that in female Blue-headed
      Vireos and was higher than in male Red-eyed Vireos at all breeding stages. Plasma
      PRL increased in male Red-eyed Vireos at the incubation stage and remained
      moderately elevated through the nestling and fledgling stages. In male Blue
      headed Vireos, the combination of high PRL and low T during the prenesting stage
      may promote brood patch formation and nest building, and, at later stages,
      incubation and feeding of young. In male Red-eyed Vireos, high PRL and low T
      during incubation and nestling stages may facilitate the feeding of young, as
      seen in males of other species. Our observations support the hypothesis that
      differences in paternal care reflect differences in circulating T and PRL.

PMID- 14644639
TI  - Evolutionary aspects of GnRHs, GnRH neuronal systems and GnRH receptors in
      teleost fish.
AB  - Gonadotrophin-releasing hormone (GnRH) was originally believed to be released by
      a unique set of hypophysiotrophic neurons to stimulate the release of
      gonadotrophins from the pituitary, therefore acting as a major initiator of the
      hormonal cascade controlling the reproductive axis. However, it now appears that
      each vertebrate species expresses two or three GnRH forms in multiple tissues and
      that GnRHs exert pleiotropic actions via several classes of receptors. This new
      vision of the GnRH systems arose progressively from numerous comparative studies
      in all vertebrate classes, but fish in general, and teleosts in particular, have
      often plaid a leading part in changing established concepts. To date fish still
      appear as attractive models to decipher the evolutionary mechanisms that led to
      the diversification of GnRH functions. Not only do teleosts exhibit the highest
      variety of GnRH variants, but recent data and whole genome analyses indicate that
      they may also possess multiple GnRH receptors. This paper intends to summarize
      the current situation with special emphasis on interspecies comparisons which
      provide insights into the possible evolutionary mechanisms leading to the
      diversification of GnRH functions.

PMID- 14644640
TI  - Effects of dopamine on the adrenal gland of Podarcis sicula (Reptilia,
      Lacertidae).
AB  - The effects of dopamine administration on the adrenal gland of a lizard, Podarcis
      sicula, are described. Dopamine (0.7mg/100g body wt/day for 4 consecutive days)
      raised plasma ACTH and corticosterone levels (ACTH: from the basal level of
      4.40+/-0.05-7.30+/-0.08pg/ml 24h after the fourth dopamine injection;
      corticosterone: from 3.59+/-0.03ng/ml in untreated lizards to 7.40+/-0.05ng/ml
      24h after the fourth dopamine injection), showing a stimulatory effect on the
      pituitary-interrenal axis activity. In the chromaffin tissue dopamine apparently
      enhanced the activity of PNMT enzyme; in fact a strong raise in the number of
      adrenaline cells and a decrease in the number of noradrenaline cells were
      observed, decreasing the numeric NA/A cell ratio, from 1.4/1 of control specimens
      to 0.5/1 24h after the fourth dopamine injection. At EM level, chromaffin cells
      contained both NA and A granules, as well as very clear granules (CG); CG
      granules showed granular elements ranging between 340 and 347A in diameter. These
      cells might be the morphological expression of a process of catecholamine
      resynthesis, due to a possible increase in catecholamine release, following
      exposure to dopamine.

PMID- 14644641
TI  - Seasonal variation in plasma sex steroid concentrations in juvenile American
      alligators.
AB  - Seasonal variation in plasma sex steroid concentrations is common in mature
      vertebrates, and is occasionally seen in juvenile animals. In this study, we
      examine the seasonal pattern of sex hormone concentration in juvenile American
      alligators (Alligator mississippiensis) and make a limited comparison of these
      seasonal patterns on two different lakes in Florida. Male juvenile alligators
      from a reference lake, Lake Woodruff, displayed temporal patterns in plasma
      testosterone (T) concentrations that appear to be seasonal. A similar pattern in
      plasma estradiol-17beta (E(2)) was observed in juvenile females from Lake
      Woodruff. Males had significantly elevated T concentrations during the spring and
      late summer, whereas females had elevated E(2) in the spring and late summer and
      significantly depressed E(2) concentrations during the winter. A limited 4-month
      survey of animals from contaminated Lake Apopka found a lack of such seasonality.
      These results suggest that: (1) healthy wild populations of juvenile alligators
      have a prolonged peripubescent period that is marked by seasonal hormonal cycles,
      (2) juvenile alligators exposed to environmental contaminants can lack such
      seasonal cyclicity, and (3) future studies of juvenile alligators should
      incorporate such seasonality into the experimental design.

PMID- 14644642
TI  - The synthesis and effects of prostaglandins on the ovary of the crab Oziotelphusa
      senex senex.
AB  - The possible involvement of prostaglandins in the regulation of ovarian
      development in the crab Oziotelphusa senex senex was investigated. Uptake of
      labelled arachidonic acid into the ovary of the crab was significantly greater
      than the other tissues. Prostaglandin H synthase activity was significantly
      increased in the ovary during the late vitellogenic stage when compared to
      immature ovary. The biosynthesis of different prostaglandins in the ovary was
      also measured during the crab reproductive cycle. Injection of prostaglandin
      F(2alpha) and prostaglandin E(2) significantly increased ovarian index and oocyte
      diameter in a dose-dependent manner. In contrast, injection of prostaglandin D(2)
      did not affect ovarian growth. These results demonstrate the presence of
      prostaglandin biosynthetic system in ovary of the fresh water crabs.

PMID- 14644643
TI  - Development of radioimmunoassay for bullfrog thyroid-stimulating hormone (TSH):
      effects of hypothalamic releasing hormones on the release of TSH from the
      pituitary in vitro.
AB  - A bullfrog (Rana catesbeiana) thyroid-stimulating hormone (TSH) beta-subunit
      (TSHbeta) antiserum was produced by employing a C-terminal peptide synthesized on
      the basis of the amino acid sequence deduced from bullfrog TSHbeta cDNA.
      Immunohistochemical studies revealed that the bullfrog adenohypophyseal cells
      that immunologically reacted with the anti-bullfrog TSHbeta corresponded to those
      positively stained with an antiserum against human (h) TSHbeta. The antiserum was
      used for the development of a specific and sensitive radioimmunoassay (RIA) for
      the measurement of bullfrog TSH. The sensitivity of the RIA was 0.75+/-0.07ng
      TSH/100microl assay buffer. The interassay and intraassay coefficients of
      variation were 7.6 and 5.3%, respectively. Several dilutions of pituitary
      homogenates of larval and adult bullfrogs, or medium in which bullfrog pituitary
      cells were cultured, yielded dose-response curves that were parallel to the
      standard curve. Bullfrog prolactin, growth hormone, luteinizing hormone, follicle
      stimulating hormone, and alpha-subunit derived from glycoprotein hormones did not
      react in this assay. Immunoassayable TSH in the pituitary culture medium was
      confirmed to exist in the form of TSHbeta coupled with the alpha-subunit by an
      immunoprecipitation experiment using the TSHbeta antiserum and an alpha-subunit
      antiserum. TSH released from pituitary cells into the medium was also confirmed
      to possess a considerable activity in stimulating the release of thyroxine from
      the thyroid glands of larval bullfrogs in vitro. The effects of hypothalamic
      hormones such as mammalian gonadotropin-releasing hormone (mGnRH), ovine
      corticotropin-releasing hormone (oCRH), and thyrotropin-releasing hormone (TRH)
      on the release of TSH by dispersed anterior pituitary cells of the bullfrog
      larvae and adults were also studied. CRH markedly stimulated the release of TSH
      from both adult and larval pituitary cells. Both TRH and GnRH moderately
      stimulated the release of TSH from adult pituitary cells but not from the larval
      cells. This is the first report on the development of an RIA for amphibian TSH,
      which has provided the direct evidence that the release of TSH from the amphibian
      pituitary is enhanced by the hypothalamic releasing hormones such as CRH, TRH,
      and GnRH.

PMID- 14644644
TI  - Non-invasive monitoring of fecal androgens in spotted hyenas (Crocuta crocuta).
AB  - Spotted hyenas (Crocuta crocuta) exhibit an array of behavioral and morphological
      characteristics that set them apart from other mammals: females are heavier and
      more aggressive than males, and females have external genitalia that closely
      resemble those of the male. Because androgenic hormones might mediate the
      expression of these traits, androgens are of great interest in this species. Past
      work on circulating androgens in wild hyenas has been limited, in part because of
      small sample sizes. In this study we validated a non-invasive method of
      monitoring variation in androgens by measuring total androgen metabolites in the
      feces of wild and captive spotted hyenas with an enzyme immunoassay. HPLC
      analysis revealed multiple immunoreactive androgen metabolites in fecal extracts
      from both males and females. LHRH challenge in three male and two female hyenas
      in captivity caused an increase in fecal androgens one to three days after LHRH
      injection. Furthermore, presence of bone in the diet did not affect fecal
      androgen concentrations in captive female hyenas. In wild spotted hyenas, time of
      day of fecal deposition, time elapsed between deposition and freezing of the
      sample, and time elapsed between freezing and extraction did not systematically
      affect fecal androgen concentrations. Finally, in wild hyenas, fecal androgen
      patterns mirrored plasma testosterone patterns in that adult immigrant males had
      higher concentrations than adult natal males, and pregnant females had higher
      concentrations than lactating females. These methods can therefore be used in
      future studies addressing relationships among fecal androgens, social status,
      reproductive state, and behavior in spotted hyenas.

PMID- 14644645
TI  - The effect of PACAP on rhythmic melatonin release of avian pineals.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous member
      of the VIP/secretin/glucagon bioactive peptide family. The distribution,
      concentration of PACAP, and its role in the control of rhythmic melatonin (MT)
      secretion from chicken pineal gland were studied. In the chicken pineal gland
      (ChPG), 40ng PACAP/g tissue was measured with radioimmunoassay. No midday
      midnight differences in the PACAP content of the ChPG could be detected.
      Immunohistochemical studies of ChPG showed PACAP immunoreactive nerve fibers in
      the perivascular space and around the pinealocytes. Neither PACAP-labeled
      perikarya nor PACAP immunopositivity in the pinealocytes could be detected. In
      five day perifusion experiments, carried out under darkness, both MT and cAMP
      showed circadian rhythmic release pattern from explanted ChPG. One hour exposure
      of ChPG to PACAP induced transient (3-4h) elevation of MT and cAMP release. The
      responses were dose-dependent in the range from 1 to 100nM PACAP concentrations.
      The magnitude of the response was independent on the phase of the daily cycle in
      which PACAP was applied. cAMP levels during normal daily cycle and also PACAP
      induced cAMP responses always preceded similar changes of MT by about an hour
      suggesting that cAMP is an intracellular intermediate in controlling MT release
      from the ChPG. At the same time PACAP, similarly to VIP, did not shift the phase
      of the in vitro circadian MT rhythm of the pineals. Our data reveal, that PACAP
      is present in nerve fibers in the chicken pineals and pineal cells contain
      functioning PACAP-sensitive receptors. PACAP apparently exerts a modulatory
      effect of the rhythmic MT release from the chicken pineal but does not modify the
      intrinsic biological clock in the avian pineal gland. Thus, cAMP-mediated
      intracellular mechanisms in ChPG are not components of the pineal circadian
      clock, but intermediaries between the clock-mechanism and MT release and may also
      be components of clock-independent MT release modifiers.

PMID- 14644646
TI  - Relationship between changes in mRNAs of the genes encoding steroidogenic acute
      regulatory protein and P450 cholesterol side chain cleavage in head kidney and
      plasma levels of cortisol in response to different kinds of acute stress in the
      rainbow trout (Oncorhynchus mykiss).
AB  - In this study, the expression of several genes involved in cortisol synthesis in
      head kidneys, the site of cortisol production, and in the rainbow trout
      (Oncorhynchus mykiss) was examined in response to two different acute stressors
      and an acute ACTH treatment. mRNAs levels of the "steroidogenic acute regulatory"
      (StAR) sterol transport protein, which transports cholesterol to the inner
      mitochondrial membrane as well as cytochrome P450 cholesterol side chain cleavage
      (P450(SCC)) were determined in head kidney (containing the interrenal tissue). In
      one experiment, we also quantified 3-beta-hydroxysteroid dehydrogenase (3B-HSD)
      and cytochrome P450(11beta) (11B-H) mRNAs. The presence of these four transcripts
      in the head kidney was confirmed by Northern blot analysis. For each stress
      condition, mRNA levels were quantified by quantitative or real-time RT-PCR. The
      results of these two methods were highly correlated. An acute stress induced by
      capture, short confinement (2min), and anesthesia (3min) resulted in significant
      elevation of plasma cortisol (30-fold higher than controls) and an increase in
      levels of StAR and P450(SCC) mRNAs 3h post-stress. When fish were submitted to an
      acute stress caused by 5min of chase with a net in a tank, plasma cortisol
      reached a peak within 1h, but after 3h, levels were only 5-fold higher in
      stressed trout than in controls and no variations in the expression of StAR,
      P450(SCC), 3B-HSD, and 11B-H were observed whatever the time post-stress. One
      hour after acute ACTH stimulation (5IU/kg), plasma cortisol level was 4-fold
      higher than in control trout and no changes in StAR and P450(SCC) mRNAs levels
      were detected. The data suggest that the high levels of cortisol after stress
      need an activation of genes involved in cortisol synthesis, but lower levels do
      not. Futhermore, under these three test conditions, we always found a strong
      positive correlation between mRNA levels of StAR and P450(SCC), in contrast to
      what has been described in mammals. Consequently, the absence of transcription
      activation with low increase in cortisol levels suggests that other levels of
      regulation, particularly activation of pre-existing proteins, govern cortisol
      production.

PMID- 14644647
TI  - Role of the adrenal gland in early post-hatching differentiation of alternative
      male phenotypes in the tree lezard (Urosaurus ornatus).
AB  - During development, sex steroids are important in establishing differences
      between males and females. However, sex steroids also are involved in the
      development and maintenance of individual differences in morphology and behavior
      within each sex. As adults, male tree lizards (Urosaurus ornatus) exhibit
      alternative reproductive tactics correlated with dewlap (throat fan) coloration.
      Males with orange-blue dewlaps are aggressive and territorial, whereas males with
      orange dewlaps are less aggressive and employ a satellite strategy. Dewlap
      coloration develops within the first 90 days after hatching and remains fixed
      throughout life. Recent work demonstrates that individual males differ in
      progesterone and testosterone secretion during development, suggesting that these
      hormones regulate the development of alternative male phenotypes. The current
      work uses in vitro incubation of adrenal and gonadal tissues to identify the
      source of progesterone and testosterone during the period of male differentiation
      and to follow ontogenetic changes in hormone release. The results indicate that,
      in all developmental stages sampled, adrenal incubations primarily contain
      progesterone and corticosterone whereas gonadal incubations contain primarily
      testosterone. These data indicate that the hatchling adrenal is the primary
      source of progesterone during early post-hatching development. Since progesterone
      has been demonstrated to play a role in the establishment of individual
      differences in morphology and behavior in male tree lizards, our results suggest
      that the hatchling adrenal gland plays an important role in post-hatching
      development of alternative male phenotypes.

PMID- 14644648
TI  - Changes in plasma concentrations of immunoreactive ouabain in the tilapia in
      response to changing salinity: is ouabain a hormone in fish?
AB  - Ouabain, a cardiac glycoside and inhibitor of Na(+), K(+)-ATPase, is now believed
      to be a steroid hormone in mammals, involved in blood pressure and volume
      regulation and possibly acting as a natriuretic hormone. We have identified
      ouabain-like immunoreactivity in the plasma and tissues of a euryhaline teleost,
      the tilapia (Oreochromis mossambicus), by means of solid-phase extraction
      followed by a specific radioimmunoassay. Plasma concentrations of immunoreactive
      ouabain were 5-20pg/ml. Ouabain immunoreactivity was detected in all the tissues
      examined, with highest concentrations in the head kidney followed by intestine
      and body kidney. When the fish in fresh water were transferred to seawater,
      plasma osmolality increased significantly after 2, 4, 8, and 24h. Significant
      increases were observed in plasma ouabain immunoreactivity after 4 and 24h, and a
      significant correlation was seen between ouabain immunoreactivity and plasma
      osmolality. There was also a significant correlation between the plasma
      osmolality and cortisol concentrations. Upon transfer from seawater to fresh
      water, significant increases were seen in plasma cortisol after 4 and 8h and in
      immunoreactive ouabain after 4h. When the correlation was analyzed using all the
      data obtained during the two transfer experiments, plasma ouabain
      immunoreactivity and cortisol were significantly correlated with plasma
      osmolality, whereas there was a significant negative correlation between plasma
      prolactin and osmolality. A significant positive correlation was also seen
      between plasma cortisol and ouabain immunoreactivity. These results suggest that
      immunoreactive ouabain may be involved, together with cortisol, in the
      maintenance of hydromineral balance in the tilapia.

PMID- 14644649
TI  - Validation of a minimally invasive blood-sampling technique for the analysis of
      hormones in domestic rabbits, Oryctolagus cuniculus (Lagomorpha).
AB  - Previous studies in small mammals showed that blood-sucking bugs (Reduviidae,
      Heteroptera) can be used to obtain blood from veins difficult to access by human
      experimenters. In the present study, we validated the use of reduviid bugs for
      endocrinological studies in endotherms using domestic rabbits as a model
      organism. Two processes could alter the hormone concentrations in the blood
      ingested by the bug: (1) Mixing of ingested blood with saliva, gut fluid, or
      hemolymph and (2) digestive processes. We compared concentrations of
      progesterone, testosterone, and hydrocortisone in blood samples that were
      acquired from domestic rabbits (Oryctolagus cuniculus) by bugs (Dipetalogaster
      maxima) with hormone concentrations in blood obtained from the same individual
      rabbits with a conventional method, i.e., syringe. We found no significant
      differences in hormone concentrations between the two methods. Thus, the mixing
      effect is negligible immediately after the blood meal. In addition, we also could
      not find significant changes in concentrations of progesterone and hydrocortisone
      for up to 8h after the blood meal. Whereas levels of hydrocortisone remained
      unchanged for even 24h, progesterone levels significantly increased between eight
      and 24h. Thus, the bugs' excretory apparatus did not fractionate between water
      and hormones. Thirdly, we hypothesized that reduviid bugs impose less stress on
      the rabbits than the conventional method. We showed that deviations in
      hydrocortisone concentrations between the two blood sampling routines were lower
      when the bug method was used first and higher when the conventional method was
      used first. Thus, bugs imposed less stress on the study animals than the
      conventional method. Overall, we conclude that reduviid bugs present a minimally
      invasive method for obtaining blood from endotherm animals for endocrinological
      studies.

PMID- 14644651
TI  - In vitro effects of cortisol on the release and gene expression of prolactin and
      growth hormone in the tilapia, Oreochromis mossambicus.
AB  - Exposure to cortisol inhibits prolactin (PRL) release from the tilapia pituitary
      within 10-20min through a plasma membrane-associated, non-genomic pathway. In the
      present study, in vitro effects of cortisol on the release and mRNA levels of two
      PRLs (PRL(188) and PRL(177)) and growth hormone (GH) were examined in the organ
      cultured pituitary of the Mozambique tilapia, Oreochromis mossambicus. The PRL
      release was significantly greater in hyposmotic (300mOsmolal) than in
      hyperosmotic (350mOsmolal) medium during the 2-8h of incubation. The mRNA levels
      of two PRLs, as estimated by RNase protection assay, were increased after 8h in
      hyposmotic medium. Cortisol (200nM) inhibited the release of two PRLs under
      hyposmotic conditions within 1h, and the inhibitory effects lasted for 24h.
      Cortisol also reduced the gene transcription of both PRLs during 2-8h of
      incubation but not after 24h. No effect of cortisol was observed on PRL release
      or on its mRNA levels under hyperosmotic condition. There was no significant
      effect of medium osmolality on the release or mRNA levels of GH during 8h of
      incubation. However, GH release was significantly stimulated by cortisol after
      4h, and the effect lasted for 24h under both hyposmotic and hyperosmotic
      conditions. Cortisol also caused a significant increase in GH mRNA levels at 8
      and 24h. These results suggest that cortisol inhibits PRL release from the
      tilapia pituitary through non-genomic and also through transcriptional pathways,
      while stimulating GH release through classical genomically mediated
      glucocorticoid actions.

PMID- 14644650
TI  - Follistatin suppresses FSHbeta but increases LHbeta expression in the goldfish -
      evidence for an activin-mediated autocrine/paracrine system in fish pituitary.
AB  - Our previous study demonstrated that recombinant goldfish activin B stimulated
      goldfish FSHbeta but inhibited LHbeta expression. Similar to activin B, activin A
      also exhibited the inverse effects on the expression of the two gonadotropins.
      The novel dual effects of activins on FSH and LH in the goldfish raise an
      interesting question as to where the activin comes from in vivo. In the present
      study, we first demonstrated the expression of activin, its receptors and binding
      protein follistatin in the goldfish pituitary, leading to a suggestion that an
      autocrine/paracrine regulatory system involving activin is operative in fish
      pituitary. To investigate the functionality of the pituitary-derived activin
      system in the regulation of gonadotropin biosynthesis, we further examined the
      effects of follistatin, an activin-binding protein, on goldfish FSHbeta and
      LHbeta expression. Follistatin not only reversed the effects of exogenous activin
      on FSHbeta and LHbeta expression but also had inverse effects on the basal
      expression of the genes; and its effects were opposite to those of activin. This
      suggests that the endogenous activin plays roles in controlling the expression of
      both FSHbeta and LHbeta genes. It is conceivable that any factors that influence
      the intrapituitary activin system in vivo will likely affect the biosynthesis of
      the two gonadotropins in the goldfish.

PMID- 14644652
TI  - Differential release of alpha-melanophore stimulating hormone isoforms by the
      pituitary gland of red porgy, Pagrus pagrus.
AB  - The best known actions of the pleiotrope alpha-melanophore stimulating hormone
      (alpha-MSH) are skin pigment regulation and corticotrope actions in the response
      to chronic stress. Stress-induced and enhanced release of alpha-MSH may therefore
      influence skin pigmentation and stress physiology simultaneously. The release of
      alpha-MSH is under multiple control by hypothalamic hormones and
      neurotransmitters. Thyrotropin releasing hormone (TRH), corticotropin releasing
      hormone (CRH), melanophore concentrating hormone (MCH), and dopamine (DA) have
      been tested in a superfusion set up for their potential to regulate alpha-MSH
      release from the pituitary gland of red porgy, Pagrus pagrus, in vitro. The
      release of alpha-MSH was stimulated by TRH and CRH, and was inhibited by MCH and
      DA. During unstimulated (basal) release, mono-acetylated alpha-MSH was the
      dominant form. During superfusion with secretagogues, we found that independent
      of their inhibitory or stimulatory capacity, isoform frequency did not change.
      MSH-isoform ratios were similar for all the substances that were used, except
      that both the inhibitory and the stimulatory factors increased the percentage of
      di-acetylated alpha-MSH at low concentrations (10(-11)M) when compared to their
      effects at high concentrations (10(-7)M).

PMID- 14644653
TI  - The toad iris assay: a simple method for evaluating CRH action on the sympathetic
      nervous system.
AB  - Corticotropin-releasing hormone (CRH) plays a key role in the regulation of
      stress and arousal associated behaviors in mammals, and contributes to
      hyperglycemia and activation of the sympathetic nervous system (SNS) during
      stress. Whether CRH regulates SNS activity in nonmammals has not been well
      studied. Here we used the iris assay to determine the ability of ovine CRH (oCRH)
      to influence SNS activity in the Texas toad, Bufo speciosus. In the toad iris
      assay, relaxation of the sphincter pupillae muscles in the iris is determined by
      measuring treatment-related changes in pupillary dilatation. A single dose of
      oCRH administered via the dorsal lymph sac increased pupillary dilatation within
      30min after administration. The stimulatory effects of oCRH on pupillary
      dilatation were dose- and time-dependent, were blocked with the CRH-receptor
      antagonist alpha-helical CRH, were associated with elevated plasma
      norepinephrine, and were not blocked by hypophysectomy. Isoproterenol, a beta
      adrenergic receptor agonist, increased pupillary dilatation in a dose-related
      fashion. The effects of isoproterenol and oCRH were blocked by the beta
      adrenergic receptor antagonist propranolol. We conclude that the toad iris assay
      is a simple but effective method for assessing CRH receptor regulation of the
      SNS.

PMID- 14644654
TI  - Molecular cloning and characterization of an amphibian progesterone receptor from
      Rana dybowskii.
AB  - Progesterone plays a pivotal role in the regulation of reproduction in all
      vertebrates and binds to nuclear hormone receptor, one of ligand-dependent
      transcription factors. Although avian and mammalian progesterone receptors (PR)
      have been well characterized, detail structure and function of amphibian
      progesterone receptor in wild frog is poorly studied yet. Here we report the
      cloning and characterization of a novel progesterone receptor from the Korean
      frog, Rana dybowskii. The R. dybowskii progesterone receptor (dyPR, GenBank
      Accession No. AF431813) cDNA isolated from testis encodes a protein of 711 amino
      acids which shows approximately 60% overall identity with the Xenopus
      progesterone receptor. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      demonstrates that dyPR is expressed in all the tissues examined. Electrophoretic
      mobility shift assays demonstrate that this receptor specifically binds to a
      progesterone response element (PRE), and transient transfection studies
      demonstrate that dyPR significantly activates the transcription of a PRE
      containing reporter element. Finally, confocal microscopy demonstrates the
      localization of this protein in nucleus, cytoplasm, and plasma membrane in
      transiently transfected CV-1 cell. These results indicate that dyPR cDNA encodes
      a classical progesterone receptor and molecular characterization of dyPR may
      provide us new information about the evolution of steroid hormone receptor.

PMID- 14644655
TI  - A second insulin gene in fish genomes.
AB  - The recent characterization of diverse vertebrate genomes has revealed the
      importance of gene duplication in vertebrate evolution. Evidence suggests that a
      genome duplication event occurred on the lineage leading to teleost fish-species
      that are often used to understand human biology. The existence of a genome
      duplication event complicates the use of fish as a model for human diseases as
      there are often two fish homologues for a single copy human gene. Often the
      second homologue has not been recognized. Our searches of the near complete
      zebrafish and fugu fish genomes indicate that both species have two insulin
      genes. Phylogenetic analysis indicates that the two genes are likely the product
      of the fish-specific genome duplication. The maintenance of two insulin genes
      within the fish suggests that the two genes have different functions. Thus the
      well-characterized insulin genes in some fish species may not be complete
      homologues of the human insulin gene.

PMID- 14644656
TI  - Molecular cloning of proopiomelanocortin cDNA in the ratfish, a holocephalan.
AB  - Proopiomelanocortin (POMC) is a precursor for several pituitary hormones
      including adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH) and
      endorphin (END). Fish POMCs in four taxonomic classes, Cephalaspidomorphi
      (lampreys), Chondrichthyes (cartilaginous fish), Sarcopterygii (lobe-finned
      fish), and Actinopterygii (ray-finned fish) have been identified. However, two
      essential species, ratfish in Chondrichthyes and hagfish in Agnatha, are still
      missing in the evolutionary image of this molecule. The present study reports
      analysis of POMC cDNA in the ratfish, Chimaera phantasma, which belongs to
      another subclass in the Chondrichthyes. Partial cDNA clones were amplified by PCR
      from single-strand cDNA prepared on total RNA from a complex of pituitary and
      hypothalamus, and subsequently overlapped to obtain a full-length sequence.
      Ratfish POMC cDNA consists of 1294bp excluding the poly(A) tail. It encodes a
      signal peptide of 25 amino acids and POMC of 300 amino acids. gamma-MSH, ACTH,
      alpha-MSH, delta-MSH, beta-MSH, and beta-END are located at prePOMC (76-87), (120
      158), (120-132), (212-227), (275-290), and (293-325), respectively. delta-MSH,
      originally found in elasmobranch POMCs, was also present in ratfish POMC,
      suggesting this structure might have appeared after the divergence of
      chondrichthians from the ancestral lineage. Thus, we demonstrated the common
      occurrence of four MSHs in chondrichthian POMC and established a clear
      understanding of the molecular evolution of POMC in gnathostomes.

PMID- 14644657
TI  - Strategies for setting a national research agenda that is responsive to community
      needs.
AB  - Setting a national environmental health research agenda requires broad public
      input, including that from leading scientists, health care professionals, and
      communities. Contributions from these diverse constituencies are essential to
      formulating a research and education strategy that both advances our
      understanding of the causes and mechanisms of environmentally related diseases
      and translates such findings into effective prevention and clinical applications
      to protect those most affected by adverse environmental exposures. Given the
      increasing number of individual researchers working with communities to address
      environmental health needs during the past decade, it is also essential for
      research institutions to foster relationships with communities to understand and
      respond to their unique public health needs, as well as to communicate research
      advances in a manner that is both understandable and culturally appropriate. To
      achieve broad public input and to foster community-university partnerships, the
      National Institute of Environmental Health Sciences (NIEHS) supports various
      workshops, roundtables, and advisory groups. In particular, the NIEHS finds Town
      Meetings to be a successful model for bringing academic researchers together with
      community residents, state and local departments of health, and community-based
      organizations to foster greater awareness of community needs, public health
      needs, and environmental health science research. Since 1998, the NIEHS has
      supported 16 Town Meetings across the country. In this article we highlight the
      major outcomes of these meetings to demonstrate the effectiveness of this
      mechanism for enhancing cooperation among researchers, community residents, and
      public health officials with the goal of improving public health and setting a
      national research agenda.

PMID- 14644658
TI  - Health, wealth, and air pollution: advancing theory and methods.
AB  - The effects of both ambient air pollution and socioeconomic position (SEP) on
      health are well documented. A limited number of recent studies suggest that SEP
      may itself play a role in the epidemiology of disease and death associated with
      exposure to air pollution. Together with evidence that poor and working-class
      communities are often more exposed to air pollution, these studies have
      stimulated discussion among scientists, policy makers, and the public about the
      differential distribution of the health impacts from air pollution. Science and
      public policy would benefit from additional research that integrates the theory
      and practice from both air pollution and social epidemiologies to gain a better
      understanding of this issue. In this article we aim to promote such research by
      introducing readers to methodologic and conceptual approaches in the fields of
      air pollution and social epidemiology; by proposing theories and hypotheses about
      how air pollution and socioeconomic factors may interact to influence health,
      drawing on studies conducted worldwide; by discussing methodologic issues in the
      design and analysis of studies to determine whether health effects of exposure to
      ambient air pollution are modified by SEP; and by proposing specific steps that
      will advance knowledge in this field, fill information gaps, and apply research
      results to improve public health in collaboration with affected communities.

PMID- 14644659
TI  - Developmental neurotoxicity elicited by gestational exposure to chlorpyrifos:
      when is adenylyl cyclase a target?
AB  - The developmental neurotoxicity of chlorpyrifos (CPF) involves mechanisms over
      and above cholinesterase inhibition. In the present study, we evaluated the
      effects of gestational CPF exposure on the adenylyl cyclase (AC) signaling
      cascade, which regulates the production of cyclic AMP, a major controller of cell
      replication and differentiation. In addition to basal AC activity, we assessed
      the AC response to direct enzymatic stimulants [forskolin, manganese (Mn(2+))];
      the response to isoproterenol, which activates signaling through beta
      adrenoceptors (betaARs); and the concentration of betaAR binding sites. CPF
      administered to pregnant rats on gestational days (GD) 9-12 elicited little or no
      change in any components of AC activity or betaARs. However, shifting the
      treatment window to GD17-20 produced regionally selective augmentation of AC
      activity. In the brainstem, the response to forskolin or Mn(2+) was markedly
      stimulated by doses at or below the threshold for observable toxicity of CPF or
      for inhibition of fetal brain cholinesterase, whereas comparable effects were
      seen in the forebrain only at higher doses. In addition, low doses of CPF reduced
      betaAR binding without impairing receptor-mediated stimulation of AC. These
      results indicate that signal transduction through the AC cascade is a target for
      CPF during a discrete developmental period in late gestation, an effect that is
      likely to contribute to the noncholinergic component of CPF's developmental
      neurotoxicity.

PMID- 14644660
TI  - Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of
      structure and cell context.
AB  - Chemoprotective phytochemicals exhibit multiple activities and interact with
      several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR).
      In this study we investigated the AhR agonist/antagonist activities of the
      following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin,
      genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and
      diosmin. We also investigated the AhR-dependent activities of cantharidin and
      emodin (in herbal extracts) in Ah-responsive MCF-7 human breast cells, HepG2
      human liver cancer cells, and mouse Hepa-1 cells transiently or stably
      transfected with plasmids expressing a luciferase reporter gene linked to
      multiple copies of a consensus dioxin-responsive element. The AhR agonist
      activities of the compounds (1 and 10 micro M) were as high as 25% of the maximal
      response induced by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their
      potencies were dependent on cell context. Galangin, genistein, daidzein, and
      diosmin were active only in Hepa-1 cells, and cantharidin induced activity only
      in human HepG2 and MCF-7 cells. Western blot analysis confirmed that baicalein
      and emodin also induced CYP1A1 protein in the human cancer cell lines. The AhR
      antagonist activities of four compounds inactive as agonists in MCF-7 and HepG2
      cells (kaempferol, quercetin, myricetin, and luteolin) were also investigated.
      Luteolin was an AhR antagonist in both cell lines, and the inhibitory effects of
      the other compound were dependent on cell context. These data suggest that
      dietary phytochemicals exhibit substantial cell context-dependent AhR agonist as
      well as antagonist activities. Moreover, because phytochemicals and other AhR
      active compounds in food are present in the diet at relatively high
      concentrations, risk assessment of dietary toxic equivalents of TCDD and related
      compounds should also take into account AhR agonist/antagonist activities of
      phytochemicals.

PMID- 14644661
TI  - Effect of bisphenol A on murine immune function: modulation of interferon-gamma,
      IgG2a, and disease symptoms in NZB X NZW F1 mice.
AB  - To investigate the effects of the estrogen receptor-binding molecule bisphenol A
      (BPA) on murine immune function in vivo, we fed a low dose of 2.5 micro g BPA/kg
      body weight/day to both normal C57BL/6 and lupus-prone NZB X NZW F(1) (NZB/NZW) 5
      week-old mice for 1 week. Analysis of concanavalin A (ConA)-stimulated splenic
      mononuclear cells by ELISA demonstrated that BPA-fed C57BL/6 males produced, on
      average, 40% less interferon-gamma (IFN-gamma; p < 0.01) and C57BL/6 females 28%
      less IFN-gamma (p < 0.05) compared with controls. Treated female NZB/NZW mice
      were monitored for lupus disease symptoms, defined as proteinuria (> 100 mg/dL
      albumin in urine for 2 consecutive weeks). Before the development of proteinuria,
      BPA-fed NZB/NZW mice produced significantly less ConA-stimulated IFN-gamma than
      did controls and displayed an average reduction of 50% in immunoglobulin G2a
      (IgG2a) antibody production from lipopolysaccharide (LPS)-stimulated splenocytes
      (p < 0.05). It is striking that 5-week-old female NZB/NZW mice fed a 7-day low
      dose course of BPA developed proteinuria an average of 7 weeks later than did
      controls. Once proteinuria developed, splenocytes were stimulated with ConA for
      cytokine analysis. The BPA-fed mice showed a dramatic reduction of 64% in IFN
      gamma production and a 32% reduction in ConA-stimulated interleukin-10 (p <
      0.05). The long-lasting effects of BPA on IFN-gamma and IgG2a production likely
      contributed to the increased symptom-free period of the NZB/NZW mice.

PMID- 14644662
TI  - Profile of urinary arsenic metabolites during pregnancy.
AB  - Chronic exposure to inorganic arsenic (In-As) from drinking water is associated
      with different health effects, including skin, lung, bladder, and kidney cancer
      as well as vascular and possibly reproductive effects. In-As is metabolized
      through the process of methylation, resulting in the production and excretion of
      methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA).
      Because a large percentage of the dose is excreted in urine, the distribution of
      urinary In-As, MMA, and DMA is considered a useful indicator of methylation
      patterns in human populations. Several factors affect these patterns, including
      sex and exposure level. In this study, we investigated the profile of urinary In
      As, MMA, and DMA of pregnant women. Periodic urine samples were collected from
      early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who
      drank tap water containing 40 micro g/L In-As. The total urinary arsenic across
      four sampling periods increased with increasing weeks of gestation, from an
      initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was
      mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA
      and a higher percentage of DMA. Our findings indicate that among women exposed to
      moderate arsenic from drinking water during pregnancy, changes occur in the
      pattern of urinary arsenic excretion and metabolite distribution. The toxicologic
      significance of this is not clear, given recent evidence suggesting that
      intermediate methylated species may be highly toxic. Nevertheless, this study
      suggests that arsenic metabolism changes throughout the course of pregnancy,
      which in turn may have toxicologic effects on the developing fetus. Key words:
      arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary
      arsenic.

PMID- 14644664
TI  - The level of maternal methemoglobin during pregnancy in an air-polluted
      environment.
AB  - The objective of this prospective study was to determine if a correlation could
      be established between the ground-level concentrations of sulfur dioxide and
      methemoglobin concentrations in pregnant women when a coal-powered thermoelectric
      power plant was in operation ("dirty" period) and when it was closed ("clean"
      period). The location of the power plant, Plomin 1, in Labin, Croatia, was taken
      into consideration. Blood and urine samples of each pregnant woman in the study
      were tested three times in the clean period (n = 138) and three times in the
      dirty period (n = 122), with 1 month between each test. I observed a correlation
      between the increase in mean values of methemoglobin and the ground-level
      concentration of SO(2) on corresponding dates during the dirty period (r = 0.72,
      p < 0.01). In the clean period, the negative mean value of methemoglobin was
      significant (r = -0.60, p <or=0.05), whereas in the dirty period, the positive
      mean value of methemoglobin was significant (r = 0.73, p 0.01). The increase of
      maternal methemoglobin could be a useful biomarker to determine when the health
      of pregnant women is threatened by toxic substances in the environment.

PMID- 14644663
TI  - Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red
      Cross adult blood donors.
AB  - Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper
      and packaging treatments, and surface protectants (e.g., for carpet, upholstery,
      textile). Depending on the specific functional derivatization or degree of
      polymerization, such products may degrade or metabolize, to an undetermined
      degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product
      that has the potential to bioaccumulate. In this investigation, a total of 645
      adult donor serum samples from six American Red Cross blood collection centers
      were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray
      tandem mass spectrometry. PFOS concentrations ranged from the lower limit of
      quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95%
      confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males
      (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3).
      No substantial difference was observed with age. The estimate of the 95%
      tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The
      measures of central tendency for the other fluorochemicals (N-ethyl
      perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate,
      perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide,
      perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of
      magnitude lower than PFOS. Because serum PFOS concentrations correlate with
      cumulative human exposure, this information can be useful for risk
      characterization.

PMID- 14644665
TI  - Biomonitoring of chemical exposure among New York City firefighters responding to
      the World Trade Center fire and collapse.
AB  - The collapse of the World Trade Center (WTC) on 11 September 2001 exposed New
      York City firefighters to smoke and dust of unprecedented magnitude and duration.
      The chemicals and the concentrations produced from any fire are difficult to
      predict, but estimates of internal dose exposures can be assessed by the
      biological monitoring of blood and urine. We analyzed blood and urine specimens
      obtained from 321 firefighters responding to the WTC fires and collapse for 110
      potentially fire-related chemicals. Controls consisted of 47 firefighters not
      present at the WTC. Sampling occurred 3 weeks after 11 September, while fires
      were still burning. When reference or background ranges were available, most
      chemical concentrations were found to be generally low and not outside these
      ranges. Compared with controls, the exposed firefighters showed significant
      differences in adjusted geometric means for six of the chemicals and
      significantly greater detection rates for an additional three. Arrival time was a
      significant predictor variable for four chemicals. Special Operations Command
      firefighters (n = 95), compared with other responding WTC firefighters (n = 226),
      had differences in concentrations or detection rate for 14 of the chemicals.
      Values for the Special Operations Command firefighters were also significantly
      different from the control group values for these same chemicals and for two
      additional chemicals. Generally, the chemical concentrations in the other
      firefighter group were not different from those of controls. Biomonitoring was
      used to characterize firefighter exposure at the WTC disaster. Although some of
      the chemicals analyzed showed statistically significant differences, these
      differences were generally small.

PMID- 14644666
TI  - OECD validation of the Hershberger assay in Japan: phase 2 dose response of
      methyltestosterone, vinclozolin, and p,p'-DDE.
AB  - The Organisation for Economic Co-operation and Development has initiated the
      development of new guidelines for the screening and testing of potential
      endocrine disruptors. The Hershberger assay is one of the assays selected for
      validation based on the need for in vivo screening to detect androgen agonists or
      antagonists by measuring the response of five sex accessory organs and tissues of
      castrated juvenile male rats: the ventral prostate, the seminal vesicles with
      coagulating glands, the levator ani and bulbocavernosus muscle complex, the
      Cowper's glands, and the glans penis. The phase 1 feasibility demonstration stage
      of the Hershberger validation program has been successfully completed with a
      single androgen agonist and a single antagonist as reference substances. The
      phase 2 validation program employs a range of additional androgen agonists and
      antagonists as well as 5alpha-reductase inhibitors. Seven Japanese laboratories
      have contributed phase 2 validation studies of the Hershberger assay using
      methyltestosterone, vinclozolin, and 2,2-bis (4-chlorophenyl)-1,1
      dichloroethylene (p,p'-DDE). The methyltestosterone doses were 0, 0.05, 0.5, 5,
      and 50 mg/kg/day, and the vinclozolin and p,p'-DDE doses were 0, 3, 10, 30, and
      100 mg/kg/day. All chemicals were orally administered by gavage for 10
      consecutive days. In the antagonist version of the assay using vinclozolin and
      p,p'-DDE, 0.2 mg/kg/day of testosterone propionate was coadministered by
      subcutaneous injection. All five accessory sex preproductive organs and tissues
      consistently responded with statistically significant changes in weight within a
      narrow window. Therefore, the Japanese studies support the Hershberger assay as a
      reliable and reproducible screening assay for the detection of androgen agonistic
      and antagonistic effects.

PMID- 14644667
TI  - The type B brevetoxin (PbTx-3) adversely affects development, cardiovascular
      function, and survival in Medaka (Oryzias latipes) embryos.
AB  - Brevetoxins are produced by the red tide dinoflagellate Karenia brevis. The
      toxins are lipophilic polyether toxins that elicit a myriad of effects depending
      on the route of exposure and the target organism. Brevetoxins are therefore
      broadly toxic to marine and estuarine animals. By mimicking the maternal route of
      exposure to the oocytes in finfish, we characterized the adverse effects of the
      type B brevetoxin brevetoxin-3 (PbTx-3) on embryonic fish development and
      survival. The Japanese rice fish, medaka (Oryzias latipes), was used as the
      experimental model in which individual eggs were exposed via microinjection to
      various known concentrations of PbTx-3 dissolved in an oil vehicle. Embryos
      injected with doses exceeding 1.0 ng/egg displayed tachycardia, hyperkinetic
      twitches in the form of sustained convulsions, spinal curvature, clumping of the
      erythrocytes, and decreased hatching success. Furthermore, fish dosed with toxin
      were often unable to hatch in the classic tail-first fashion and emerged head
      first, which resulted in partial hatches and death. We determined that the LD(50)
      (dose that is lethal to 50% of the fish) for an injected dose of PbTx-3 is 4.0
      ng/egg. The results of this study complement previous studies of the
      developmental toxicity of the type A brevetoxin brevetoxin-1 (PbTx-1), by
      illustrating in vivo the differing affinities of the two congeners for cardiac
      sodium channels. Consequently, we observed differing cardiovascular responses in
      the embryos, wherein embryos exposed to PbTx-3 exhibited persistent tachycardia,
      whereas embryos exposed to PbTx-1 displayed bradycardia, the onset of which was
      delayed.

PMID- 14644669
TI  - Silica exposure and systemic vasculitis.
AB  - Work in Department of Energy (DOE) facilities has exposed workers to multiple
      toxic agents leading to acute and chronic diseases. Many exposures were common to
      numerous work sites. Exposure to crystalline silica was primarily restricted to a
      few facilities. I present the case of a 63-year-old male who worked in DOE
      facilities for 30 years as a weapons testing technician. In addition to silica,
      other workplace exposures included beryllium, various solvents and heavy metals,
      depleted uranium, and ionizing radiation. In 1989 a painful macular skin lesion
      was biopsied and diagnosed as leukocytoclastic vasculitis. By 1992 he developed
      gross hematuria and dyspnea. Blood laboratory results revealed a serum creatinine
      concentration of 2.1 mg/dL, ethrythrocyte sedimentation rate of 61 mm/hr,
      negative cANCA (antineutrophil cytoplasmic antibody cytoplasmic pattern),
      positive pANCA (ANCA perinuclear pattern), and antiglomerular basement membrane
      negative. Renal biopsy showed proliferative (crescentric) and necrotizing
      glomerulonephritis. The patient's diagnoses included microscopic polyangiitis,
      systemic necrotizing vasculitis, leukocytoclastic vasculitis, and
      glomerulonephritis. Environmental triggers are thought to play a role in the
      development of an idiopathic expression of systemic autoimmune disease.
      Crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma,
      systemic lupus erythematosus, rapidly progressive glomerulonephritis and some of
      the small vessel vasculitides. DOE workers are currently able to apply for
      compensation under the federal Energy Employees Occupational Illness Compensation
      Program (EEOICP). However, the only diseases covered by EEOICP are cancers
      related to radiation exposure, chronic beryllium disease, and chronic silicosis.

PMID- 14644668
TI  - Hazardous effects of effluent from the chrome plating industry: 70 kDa heat shock
      protein expression as a marker of cellular damage in transgenic Drosophila
      melanogaster (hsp70-lacZ).
AB  - Hazardous effects of an effluent from the chrome plating industry were examined
      by exposing transgenic Drosophila melanogaster (hsp70-lacZ) to various
      concentrations (0.05, 0.1, 1.0, 10.0, and 100.0 micro L/mL) of the effluent
      through diet. The emergence pattern of adult flies was affected, along with
      impaired reproductive performance at the higher dietary concentrations of the
      effluent. Interestingly, the effect of the effluent was more pronounced in male
      than in female flies. The effect of the effluent on development of adult flies
      was concurrent with the expression pattern of the heat shock protein 70 gene
      (hsp70), both in larval tissues and in the reproductive organs of adult flies. We
      observed a dose- and time-dependent expression of hsp70 in third instar larvae
      exposed for different time intervals. Absence of hsp70 expression in larvae
      exposed to 0.1 micro L/mL of the effluent indicated that this is the highest
      nontoxic concentration for Drosophila. The stress gene assay in the reproductive
      organs of adult flies revealed hsp70 expression in the testis of male flies only.
      However, trypan blue dye exclusion tests in these tissues indicate tissue damage
      in the male accessory gland of adult flies, which was further confirmed by
      ultrastructural observations. In the present study we demonstrate the utility of
      transgenic Drosophila as an alternative animal model for evaluating hazardous
      effects of the effluent from the chrome plating industry and further reveal the
      cytoprotective role of hsp70 and its expression as an early marker in
      environmental risk assessment.

PMID- 14644670
TI  - Use of biomarkers to indicate exposure of children to organophosphate pesticides:
      implications for a longitudinal study of children's environmental health.
AB  - Because of their history of widespread use in the United States and unknown long
      term health effects, organophosphate pesticides (OPs) are being considered as a
      chemical class of interest in planning for the National Children's Study, a
      longitudinal study of children's environmental health. The availability and
      appropriate use of biomarkers to determine absorbed doses of environmental
      chemicals such as OPs are critical issues. Biomarkers of OP exposure are
      typically measured in blood and urine; however, postpartum meconium has been
      shown to be a promising matrix for assessing cumulative in utero exposure to the
      fetus, and studies are currently in progress to determine the utility of using
      saliva and amniotic fluid as matrices. In this article, we discuss the advantages
      and disadvantages of the currently available OP exposure monitoring methods
      (cholinesterase inhibition in blood, pesticides in blood, metabolites in urine
      and alternative matrices); study design issues for a large, long-term study of
      children's environmental health; and current research and future research needs.
      Because OPs are rapidly metabolized and excreted, the utility of one-time spot
      measurements of OP biomarkers is questionable unless background exposure levels
      are relatively stable over time or a specific time frame of interest for the
      study is identified and samples are collected accordingly. Biomarkers of OP
      exposure can be a valuable tool in epidemiology of children's environmental
      health, as long as they are applied and interpreted appropriately.

PMID- 14644671
TI  - A randomized trial of education to prevent lead burden in children at high risk
      for lead exposure: efficacy as measured by blood lead monitoring.
AB  - In this article we report on the effectiveness of a community-based, culture
      specific, controlled trial of intensive peer education aimed at preventing lead
      burden in children 0-36 months of age within a neighborhood with high risk for
      lead exposure. Mothers (n = 594) were randomly assigned to control or
      intervention groups. Offspring blood lead levels were assessed every 4 months.
      All participants received brochures on basic lead prevention strategies.
      Intervention participants were offered 20 bi-weekly educational sessions by same
      ethnicity peer educators over the course of 1 year, and quarterly booster
      sessions for 2 years afterward. The intervention group's educational curriculum
      included information on lead sources (e.g., paint, dust, water, soil, and risks
      from home repairs and remodeling), health consequences of lead burden, and
      strategies to reduce lead exposure, including household cleaning, hygiene, safe
      use of water, and nutritional recommendations. Results indicated that of the 378
      children contributing sufficient blood data for analysis, 23% had blood lead
      levels > 10 micro g/dL before 3 years of age. Intervention participants were more
      likely to maintain blood lead levels < 10 micro g/dL than were controls (81% vs.
      73%; p = 0.08). Multivariate analyses demonstrated that the intervention reduced
      the risk of blood lead levels > 10 micro g/dL by approximately 34%. We conclude
      that although intensive education resulted in a lower proportion of children with
      elevated lead levels, education alone cannot be relied upon to prevent lead
      burden.

PMID- 14644672
TI  - In vitro activation of cord blood mononuclear cells and cytokine production in a
      remote coastal population exposed to organochlorines and methyl mercury.
AB  - Remote coastal populations that rely on seafood for subsistence often receive
      unusually high doses of organochlorines and methyl mercury. Immunosuppression
      resulting from prenatal exposure to organochlorines has been reported in wildlife
      species and humans. In this study, we assessed lymphocyte activation and
      associated cytokine secretion in 47 newborns from a remote maritime population
      living on the Mid and Lower North Shore regions of the St. Lawrence River
      (Quebec, Canada; subsistence fishing group) and 65 newborns from nearby urban
      settings (reference group). Cord blood samples were collected for organochlorine
      and mercury analyses and also to isolate cord blood mononuclear cells (CBMCs) for
      the in vitro assessment of cytokine production and expression of surface markers
      after mitogenic stimulation (CD4(+)CD45RO(+), CD8(+)CD45RO(+), CD3(+)CD25(+), and
      CD8(+)HLA-DR(+)). Blood mercury and plasma concentrations of polychlorinated
      biphenyls (PCBs), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), and
      hexachlorobenzene (HCB) were significantly higher in the subsistence fishing
      group than in the reference group (p < 0.001). No difference was observed between
      the two groups regarding subsets of lymphocytes showing markers of activation. In
      vitro secretion of cytokines by CBMCs after mitogenic stimulation was lower in
      the subsistence fishing group than in the reference group (p < 0.05). Moreover,
      we found an inverse correlation between tumor necrosis factor-alpha (TNF-alpha)
      secretion and plasma PCB, p,p'-DDE, and HCB concentrations (p < 0.05). Our data
      support a negative association between TNF-alpha secretion by CBMCs and prenatal
      organochlorine exposure. If the relationship between organochlorine and TNF-alpha
      secretion is causal, it would suggest a role for this important proinflammatory
      cytokine in mediating organochlorine-induced immunotoxicity in infants
      developmentally exposed to these compounds.

PMID- 14644673
TI  - Effect of endosulfan on male reproductive development.
AB  - There is experimental evidence of adverse effects of endosulfan on the male
      reproductive system, but there are no human data. Therefore, we undertook a study
      to examine the relationship between environmental endosulfan exposure and
      reproductive development in male children and adolescents. The study population
      was composed of 117 male schoolchildren (10-19 years of age) of a village
      situated at the foothills of cashew plantations, where endosulfan had been
      aerially sprayed for more than 20 years, and 90 comparable controls with no such
      exposure history. The study parameters included recording of clinical history,
      physical examination, sexual maturity rating (SMR) according to Tanner stages,
      and estimation of serum levels of testosterone, luteinizing hormone (LH),
      follicle-stimulating hormone, and endosulfan residues (70 study and 47 control
      subjects). Mean +/- SE serum endosulfan levels in the study group (7.47 +/- 1.19
      ppb) were significantly higher (p < 0.001) than in controls (1.37 +/- 0.40 ppb).
      Multiple regression analysis showed that SMR scoring for development of pubic
      hair, testes, penis, and serum testosterone level was positively related to age
      and negatively related to aerial exposure to endosulfan (AEE; p < 0.01). Serum LH
      levels were significantly positively related to AEE after controlling for age (p
      < 0.01). The prevalence of congenital abnormalities related to testicular descent
      (congenital hydrocele, undescended testis, and congenital inguinal hernia) among
      study and controls subjects was 5.1% and 1.1%, respectively, but the differences
      were statistically nonsignificant. Our study results suggest that endosulfan
      exposure in male children may delay sexual maturity and interfere with sex
      hormone synthesis. Our study is limited by small sample size and
      nonparticipation.

PMID- 14644674
TI  - Human interactions are crucial for sustainable development.

PMID- 14644675
TI  - "Birth malformations and other adverse perinatal outcomes": available data
      sources pose a dilemma.

PMID- 14644676
TI  - Re: "Birth malformations and other adverse perinatal outcomes in four U.S. wheat
      producing states".

PMID- 14644678
TI  - He who pays the piper calls the tune.

PMID- 14644680
TI  - Asthma and air toxics: another potential source of positive bias.

PMID- 14644681
TI  - Another fast-food fear.

PMID- 14644682
TI  - Driving cancer research forward deep in the heart of Texas.

PMID- 14644683
TI  - Unbuilding for the environment.

PMID- 14644684
TI  - The price of life in the fast lane.

PMID- 14644685
TI  - Down with road dust.

PMID- 14644687
TI  - Sedentary older women's limited experience with exercise.
AB  - The aim of this study was to examine sedentary older women's experiences with
      exercise. Interview-administered questionnaires and physical measures assessed
      exercise history variables, health-related quality of life, functional status,
      depression, perceived vigor, adiposity, and body mass index. Women aged 65 to 97
      years (N = 198) participated in the study. Most women reported at least 1
      experience with episodic exercise but only 27% had experience with 2 forms of
      exercise and just 7% had experience with 3 exercise types. Many women began
      regular continuous exercise during their 5th, 6th, or 7th decades, but stopped
      exercising after a few years. Correlations between past exercise and potential
      health outcomes were very modest. These sedentary elderly women had very limited
      repertoires of experience with episodic exercise. Interventions designed to help
      women in their 50s, 60s, and 70s maintain the exercise programs may prove
      particularly valuable.

PMID- 14644688
TI  - The impact of adult day programs on family caregivers of elderly relatives.
AB  - Adult day programs for elderly people have been implemented throughout North
      America but not widely evaluated for their impact on family caregivers. This
      study examined caregiver outcomes at 14 programs in Alberta, Canada. Caregivers
      were measured on burden, quality of life, perceived health, opinion on
      institutionalization at 4 time points (just prior to client admission, 2 weeks, 2
      months, and 6 months after admission), and satisfaction with the program at 3
      points after client admission. Caregiver status on burden, quality of life, and
      perceived health status remained stable over time. In addition, caregivers'
      opinion on institutionalization remained negative and satisfaction with the
      programs high. Caregivers reported that client socializing and improved health
      were what they liked best about the programs, followed by respite for themselves.
      Time conflicts-limits and transportation were identified as problems. The results
      suggest that adult day programs may help caregivers to continue in their
      caregiving role and to keep clients in the community longer.

PMID- 14644690
TI  - Bereaved Orthodox Jewish families and their community: a cross-cultural
      perspective.
AB  - This article examines the laws and customs of bereavement in Orthodox Jewish
      families and their community. It considers definitions of bereavement, the need
      for health care team members' cross-cultural understanding of bereavement, the
      community's role, and the role of the community health nurse and health care team
      with this particular group.

PMID- 14644691
TI  - Evaluation informs coalition programming for environmental tobacco smoke
      reduction.
AB  - The objective for this formative evaluation was to establish baseline data for
      informing a community coalition's strategic planning in environmental tobacco
      smoke (ETS) risk reduction. The coalition had chosen 3 targeted settings for ETS
      risk reduction: restaurants, childcare facilities, and government buildings. The
      evaluation methodology involved telephone interviews (restaurants, n = 805;
      governmental buildings, n = 258) and mailed surveys (childcare facilities, n =
      1,142). Data on county residents and businesses were used for comparison purposes
      and were analyzed from the Nebraska Social Climate Survey (2001; n = 558).
      Evaluation baseline findings showed that licensed childcare facilities were more
      ETS knowledgeable, less ETS tolerant, and more smoke-free than restaurants.
      Residents were more bothered by ETS than what restaurant proprietors perceived.
      The majority of governmental buildings were not smoke-free. Conclusions were that
      community health nurse evaluators can provide coalitions with formative
      evaluative data to inform strategic planning and increase the likelihood of
      effective program interventions for community impact on ETS.

PMID- 14644692
TI  - Evidence-based behavioral medicine: what is it and how do we achieve it?
AB  - The goal of evidence-based medicine is ultimately to improve patient outcomes and
      quality of care. Systematic reviews of the available published evidence are
      required to identify interventions that lead to improvements in behavior, health,
      and well-being. Authoritative literature reviews depend on the quality of
      published research and research reports. The Consolidated Standards for Reporting
      Trials (CONSORT) Statement (www.consort-statement.org) was developed to improve
      the design and reporting of interventions involving randomized clinical trials
      (RCTs) in medical journals. We describe the 22 CONSORT guidelines and explain
      their application to behavioral medicine research and to evidence-based practice.
      Additional behavioral medicine-specific guidelines (e.g., treatment adherence)
      are also presented. Use of these guidelines by clinicians, educators,
      policymakers, and researchers who design, report, and evaluate or review RCTs
      will strengthen the research itself and accelerate efforts to apply behavioral
      medicine research to improve the processes and outcomes of behavioral medicine
      practice.

PMID- 14644693
TI  - Classification and regression tree analysis in public health: methodological
      review and comparison with logistic regression.
AB  - BACKGROUND: Audience segmentation strategies are of increasing interest to public
      health professionals who wish to identify easily defined, mutually exclusive
      population subgroups whose members share similar characteristics that help
      determine participation in a health-related behavior as a basis for targeted
      interventions. Classification and regression tree (C&RT) analysis is a
      nonparametric decision tree methodology that has the ability to efficiently
      segment populations into meaningful subgroups. However, it is not commonly used
      in public health. PURPOSE: This study provides a methodological overview of C&RT
      analysis for persons unfamiliar with the procedure. METHODS AND RESULTS: An
      example of a C&RT analysis is provided and interpretation of results is
      discussed. Results are validated with those obtained from a logistic regression
      model that was created to replicate the C&RT findings. Results obtained from the
      example C&RT analysis are also compared to those obtained from a common approach
      to logistic regression, the stepwise selection procedure. Issues to consider when
      deciding whether to use C&RT are discussed, and situations in which C&RT may and
      may not be beneficial are described. CONCLUSIONS: C&RT is a promising research
      tool for the identification of at-risk populations in public health research and
      outreach.

PMID- 14644694
TI  - Cardiovascular reactivity and left ventricular mass: an integrative review.
AB  - Left ventricular hypertrophy has been shown to be an independent predictor of
      risk for cardiovascular morbidity and mortality. Behavioral scientists have
      focused on how hemodynamic factors influenced by psychosocial stress may be
      associated with left ventricular mass (LVM). We reviewed existing studies
      examining stress-related cardiovascular reactivity (CVR) and LVM, with a goal of
      examining the moderating role of population (age and hypertensive status) and
      methodological factors (task type, sample size, and study design) explaining the
      observed results. Twenty-one studies met the criteria for this review. Results
      showed only a modestly consistent relationship between CVR and LVM. Forty-three
      percent of the studies reported 1 or more significant results linking systolic
      blood pressure reactivity with LVM, and 14% of the studies showed that diastolic
      blood pressure reactivity was significantly related to LVM. Hypertensive status,
      task type, and sample size did not play a major role in moderating the
      relationship between LVM and CVR. A somewhat larger percentage of positive
      results was shown in prospective and adult studies. The association between CVR
      and LVM may be real, although the effect size is modest, and we discuss
      methodological strategies for enhancing statistical power in future
      investigations. Additional sampling factors (e.g., race, gender) may also impact
      this relationship. Finally, greater attention is warranted to the role of the
      psychosocial environment, as this may interact with reactivity to influence LVM.

PMID- 14644695
TI  - Intraindividual variation in recent stress exposure as a moderator of cortisol
      and testosterone levels.
AB  - Intraindividual variation in recent stress exposure and its impact upon cortisol
      and testosterone was investigated. Over 1 year, 72 young male firefighters
      completed the Daily Stress Inventories, for 2 shift cycles (16 days), every 3
      months. At the end of each 16-day period each participant attended a 1-hr morning
      assessment session. Saliva samples and blood pressure measurements were taken at
      10-min intervals, and at 30 min, a blood sample was drawn. Across the year of
      assessment, there were significant linear relationships in reported stress and in
      neuroendocrine activity. In contrast to expectations, as daily stress decreased
      across the year (p <.008), salivary cortisol increased (p <.001) and testosterone
      levels decreased (p <.001). Within-subjects comparisons of the sessions with the
      highest and lowest stress confirmed these linear relationships: Lower stress
      prior to the assessment session was associated with higher cortisol levels (p
      <.01). These results, though in contrast to the orthodoxy concerning the
      association between stress and cortisol, are supported by findings in a number of
      other studies and may constitute down regulation of cortisol activity following
      an increment in stress exposure.

PMID- 14644696
TI  - Repeat mammography: prevalence estimates and considerations for assessment.
AB  - Despite recent controversies in mammography efficacy, encouraging women to obtain
      regular screenings is still an important public health priority. Published
      articles about repeat or regular screening were reviewed to determine trends in
      rates of mammography adherence. A search of MEDLINE and PsycINFO from January
      1990 to December 2001 identified 45 empirical articles of U.S. samples that
      reported, or provided sufficient data to calculate, the percentage of women 50
      years of age and older who obtained 2 or more consecutive, on-schedule
      mammograms. Keywords used in the searches included pairing mammography with
      regular, repeat, adherence, compliance, annual, rescreen, and maintenance. The
      weighted average repeat mammography percentage across all eventually included
      studies (N = 37) was 46.1% (confidence interval: 39.4%, 52.8%). There was no
      substantial difference in the average repeat screening percentages comparing
      studies that collected data from 1995 to 2001 versus 1991 to 1994. Within each of
      3 time periods of data collection (pre-1991, 1991-1994, 1995-2001), there was
      substantial variation in repeat rates. This variation appears to be due to
      several characteristics of study design and sampling, including the
      definition/methods of collecting data about the adherence measure, prior
      mammography status, and use of an upper age limit at recruitment. Consensus is
      needed regarding the definition of repeat mammography. National surveys must
      include items to assess repeat mammography in order to have estimates that
      accurately represent population-level rates. Although this study involved
      mammography, similar challenges in assessing prevalence rates can occur with
      other screening behaviors.

PMID- 14644697
TI  - Lifestyle intervention can prevent weight gain during menopause: results from a 5
      year randomized clinical trial.
AB  - CONTEXT: Menopausal-related weight gain and increased waist circumference have
      major cardiovascular health implications for older women. The efficacy of a
      dietary and physical activity lifestyle intervention to prevent weight gain and
      elevations in cardiovascular disease (CVD) risk factors from the peri- to
      postmenopause is unknown. OBJECTIVE: To report the 54-month results of a
      lifestyle dietary and physical activity program on weight, body composition,
      physical activity, diet, and other CVD risk factors. DESIGN: Data are from a 5
      year randomized clinical trial known as the Women's Healthy Lifestyle Project,
      conducted from 1992 to 1999. PARTICIPANTS: 535 healthy, premenopausal women ages
      44 to 50 at study entry enrolled into the trial. INTERVENTION: Participants were
      randomly assigned to either a lifestyle intervention group receiving a 5-year
      behavioral dietary and physical activity program or to an assessment-only control
      group. The lifestyle intervention group was given modest weight loss goals (5-15
      lb, or approximately 2.3-6.8 kg) to prevent subsequent gain above baseline weight
      by the end of the trial. To achieve weight loss and lower low-density lipoprotein
      cholesterol levels, intervention participants followed an eating pattern
      consisting of 1,300 kcal/day (25% total fat, 7% saturated fat, 100 mg of dietary
      cholesterol) and increased their physical activity expenditure (1,000-1,500
      kcal/week). MAIN OUTCOME MEASURES: Regarding weight gain prevention, 55%
      (136/246) of intervention participants were at or below baseline weight compared
      with 26% (68/261) of controls after 4.5 years, chi2(2, N = 507) =45.0, p <.001.
      The mean weight change in the intervention group was 0.1 kg below baseline (SD =
      5.2 kg) compared with an average gain of 2.4 kg (SD = 4.9 kg) observed in the
      control group. Waist circumference also significantly decreased more in the
      intervention group compared with controls (M = -2.9 cm, SD = 5.3 vs. M = -0.5 cm,
      SD = 5.6, p <.001). Moreover, participants in the lifestyle intervention group
      were consistently more physically active and reported eating fewer calories and
      less fat than controls. Long-term adherence to physical activity and a low-fat
      eating pattern was associated with better weight maintenance. CONCLUSIONS: In
      healthy women, weight gain and increased waist circumference during the peri- to
      postmenopause can be prevented with a long-term lifestyle dietary and physical
      activity intervention.

PMID- 14644698
TI  - Comments on "Challenges to improving the impact of worksite cancer prevention
      programs": paradigm lost?

PMID- 14644700
TI  - Clinical Significance of Lipoprotein Disorders in HIV-positive Patients.
      Abstracts of the 1st European Symposium. November 21-22, 2003, Munich, Germany.

PMID- 14644701
TI  - Initial RNA expression in human monocytes after multiple injury: a screening
      pilot study on potentially trauma-sensitive factors by using the microarray
      technique.
AB  - BACKGROUND: Pathological affection of the immune system is one of the initiating
      mechanisms for the induction of multiple organ failure (MOF) in patients
      suffering from multiple injuries. Potential responsible intracellular mechanisms
      such as initial monocyte mRNA expression of specific mediators remain poorly
      studied, so far. Hence, we applied the microarray technique for screening of a
      wide variety of genes in circulating monocytes of multiple injured patients and
      compare the molecular results to the clinical course of the patients (MOF-score).
      METHODS: In our prospective pilot study 6 patients were enclosed presenting with
      blunt multiple injuries (Injury Severity Score 16 to 57 points). Monocytes were
      isolated out of sequentially drawn samples (6, 12, 24 and 48 hours after trauma)
      using magnetic cell sorting (CD14) and a human microarray system was used (Atlas
      stress 1.2, Clontech, 1176 genes). Alterations in the sequential samples were
      identified by calculating ratios to baseline levels on admission and cluster
      analysis was performed (Spotfire Decision). RESULTS: Only 86 (ca.5%) genes
      displayed an obvious signal. The house-keeping genes clustered well together in
      all patients in contrast to a substantial inter-individual variability of the
      other signal giving genes. No mediator burst of the classical pro- or anti
      inflammatory cascade were detected. CONCLUSION: We demonstrate for the first time
      a screening analysis of mRNA expression patterns in circulating monocytes of
      multiple injured patients indicating that only very few genes appeared to be
      influenced by the traumatic event. So far, no correlation to the severity of
      trauma or MOF could be detected.

PMID- 14644702
TI  - Only transient increase of serum CoQ subset 10 during long-term CoQ10 therapy in
      mitochondrial ophthalmoplegia.
AB  - BACKGROUND: Coenzyme Q10 (CoQ10) is frequently administered in mitochondrial
      diseases. Mitochondrial dysfunction and CoQ10 treatment was also proposed in
      neurodegenerative disorders as amyotrophic lateral sclerosis and Parkinsons
      disease. PATIENTS AND METHODS: Seventeen patients with mitochondrial CPEO were
      treated with CoQ10 (dosage: 0.60 1.80 mg/kg body wt) in an open trial. Serum
      levels of CoQ10 were monitored before and after 6-9 and 12-15 months of CoQ10
      therapy. CoQ10 concentration in muscle was measured in all patients before
      treatment. RESULTS: Prior to treatment CoQ10 concentration in muscle was normal
      in all patients. Eight patients completed the study after 12-15 months. Prior to
      treatment there was no correlation between CoQ10 in muscle and serum. There was
      no inverse correlation of serum lactate with CoQ10 in muscle before and in serum
      before and during therapy. CoQ10 serum level and body weight related CoQ10 dosage
      correlated significantly after 6-9 months but not after 12-15 months (p = 0.043
      and n. s., respectively). During continued administration of CoQ10 the CoQ10
      serum level was increased 2.76 +/- 1.00-fold after 6-9 months (range: 1.04-3.80).
      but returned to 1.70 +/- 0.98-fold after 12-15 months (range: 0.91-3.83). Serum
      lactate did not significantly change during treatment. There was no effect of
      CoQ10 treatment on signs and symptoms. CONCLUSION: The only transient increase of
      CoQ10 in serum has to be considered in any low dose long-term treatment with
      CoQ10.

PMID- 14644703
TI  - Wernicke's encephalopathy: unusual contrast enhancement revealed by magnetic
      resonance imaging.
AB  - Wernicke's encephalopathy is a serious neurologic disorder caused by vitamin-B1
      or thiamine deficiency. The classical triad of clinical symptoms described by
      Wernicke (gait ataxia, ophthalmoplegia, and confusion) are found in only a third
      of patients upon initial examination. Typical findings upon MR imaging in
      patients with Wernicke's encephalopathy are well documented, with signal
      intensities in the medial thalami and periaqueductal regions of the midbrain. We
      report a case of Wernicke's encephalopathy revealing an unusual contrast
      enhancement. It is therefore important to note that the acute stage of Wernicke's
      encephalopathy may be associated with an intense contrast enhancement upon MR
      imaging reflecting the disruption of the blood-brain barrier and inflammatory
      processes caused by thiamine deficiency. As a consequence from the guideline for
      managing Wernicke's encephalopathy by the Royal College of Physicians early B
      vitamin treatment in suspected is recommended cases.

PMID- 14644704
TI  - Resolution of HCV infection in a HIV-infected patient under HAART after several
      hepatitis flare-ups.
AB  - Highly active antiretroviral therapy (HAART) has been shown to have a beneficial
      effect on several opportunistic and other coinfections of HIV infected
      individuals. The effect of HAART on HCV coinfections is controversial. We
      describe the case of a patient, in whom a close temporal relationship between
      changes in HIV viremia, HCV viremia and ALT levels was observed. Longterm
      suppression of HIV replication by HAART was associated with a normalization of
      ALT levels and finally clearance of the HCV infection. Our data suggest that
      improved immune functions due to reductions of the HIV load led to a better
      control and finally resolution of the HCV infection in this patient.

PMID- 14644705
TI  - Correlation between inflammatory periodontal diseases and cardiovascular
      diseases.
AB  - AIMS: Since cardiovascular diseases can exhibit a possible connection with
      chronic periodontal diseases, the aim of the present study was to examine the
      presence of periodontal impairment in patients with coronary heart diseases
      (CHD). METHODS: For this purpose periodontal charts were raised for 101 patients
      (78 male, 23 female, mean age 61.8 +/- 10.5 years) with cardiovascular diseases;
      comparison was drawn between theses charts and those for a control group of 101
      healthy patients (59 male, 42 female, mean age 56.6 +/- 9.9 years). Over and
      above the dental diagnosis (probing depth [mm], vitality, tooth mobility, plaque
      index (PI), inclination towards sulcus bleeding) each related to 6 characteristic
      teeth, various habitual aspects (diet, smoke and drink patterns, stress, body
      weight) were recorded. RESULTS: Within the CHD-group the periodontal chart
      revealed for all teeth examined a mean probing depth of 3.4 +/- 1.1mm, with the
      corresponding reading for the control group being 2.8 +/- 0.9 mm. The mean
      bleeding index (Van-der-Weiden) read 1.1 +/- 0.7 for the CHD-group and 0.7 +/-
      0.6 for the control group. The mean plaque index reading was 1.4 +/- 0.9 for the
      group suffering from heart diseases and 0.7 +/- 0.8 for the control group.
      Comparison of these periodontal charts showed statistically significant
      differences (p<= 0.01), whereas mean degrees of tooth mobility did not differ in
      a statistically significant way. In summary, the results described hint at a
      correlation between an existent coronary heart disease and the presence of a
      periodontitis. CONCLUSION: However, also for consideration below are further
      influential factors, such as diet, individual life conduct, smoking habits, Body
      Mass-Index or microbiological aspects.

PMID- 14644706
TI  - Comparison of exhaled breath condensate from nasal and oral collection.
AB  - BACKGROUND: Analysis of exhaled breath condensate may provide new insights into
      pulmonary inflammatory processes. A new collection method via suction of nasally
      expired air especially suitable for younger children was presented recently. Here
      we compare this nasal suction method with the more widely used oral collection
      method regarding the amount of condensate collected as well as the concentrations
      of hydrogen peroxide (H2O2), nitrite and nitrate, respectively. MATERIALS AND
      METHODS: Exhaled breath condensate was collected from 11 healthy adults for the
      measurements of the amount of condensate and H2O2 concentration and from 17
      children for the measurements of nitrite and nitrate. Condensate was collected
      via nasal suction and oral exhalation from each subject. RESULTS: Overall, no
      differences between both collection methods were found for all variables assessed
      except the concentration of H2O2, whereas the latter closely correlated (Spearman
      r = 0.88, p = 0.0007) between both collection methods. No correlation was found
      for the amount of condensate collected and the concentration of nitrite and
      nitrate. The Bland-Altman limits of agreement scattered over a wide range with
      clinical impact, proving significant differences between both collection methods
      for all variables measured. CONCLUSIONS: Although nasal and oral collection
      method proved again suitable for the collection of exhaled breath condensate, the
      variability of the results obtained precludes the interchangeable usage of the
      inflammatory markers assessed here.

PMID- 14644707
TI  - Postoperative ICU management in liver transplant patients.
AB  - The unique pathophysiology of end-stage liver disease (ESLD) has important
      implications on critical care treatment after liver transplantation. To determine
      hemodynamic parameters and responses, each patient must be carefully evaluated
      for the individual clinical appearance of cirrhosis and portal hypertension.
      Although data are limited, recent progress in the treatment of ESLD and its
      complications, such as hepatorenal syndrome (HRS), portopulmonary hypertension
      (PPH), and hepatopulmonary syndrome (HPS) is evident. The improved understanding
      of the pathophysiology of ESLD has resulted in novel treatments and approaches to
      the problems that emerge as patients get critically ill or undergo orthotopic
      liver transplantation (OLT). These issues become much more relevant with
      increased adult-to-adult living donor liver transplantation, where the scheduled
      operation allows a precise preoperative management in an Intensive Care Unit
      (ICU).

PMID- 14644709
TI  - Development of the National Eye Institute refractive error correction quality of
      life questionnaire: focus groups.
AB  - OBJECTIVE: To identify the content area for a questionnaire designed to measure
      the vision-targeted, health-related quality of life for persons with well
      corrected refractive error. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty
      two focus groups were conducted with 414 patients from 5 geographically diverse
      ophthalmic and optometric sites to identify the content area of a questionnaire
      for use among persons with myopia and hyperopia. METHODS: A standard protocol was
      used to structure each focus group discussion, and groups were led by centrally
      trained moderators at each participating site. Results were summarized and
      analyzed using a standard set of codes. Qualitative and quantitative analyses
      were conducted. MAIN OUTCOME MEASURE: Self-reported observations or comments
      about vision, vision correction, and other aspects of quality of life. RESULTS:
      Among the 414 participants, 9262 mentions of comments were recorded. The most
      frequent comments reported by participants were about types of vision correction,
      followed by comments with their own vision and vision-related symptoms. The
      distribution of comments by topic domain was generally similar across types of
      correction and type of refractive error. The most frequent specific comments
      about glasses concerned problems with reading, adjustment between near and far
      vision, and appearance. The most frequent comments about contact lenses included
      those on symptoms such as dry eyes, itching and tired eyes, and headaches, and
      negative comments about ease of use. The most frequent comments among patients
      with surgical correction concerned fewer driving problems; fewer symptoms; and
      improvement in vision, recreation, and comfort. Participants provided equal
      numbers of positive and negative comments about glasses. Twice as many positive
      as negative comments were given by contact lens wearers, and 4 times as many
      positive comments were provided by patients who had undergone surgical
      correction. CONCLUSIONS: Using focus groups, we were able to identify content
      areas and aspects of visual functioning in persons with refractive error that are
      not measured by standard visual acuity testing in the clinic or by other vision
      targeted, health-related quality of life instruments such as the 25- or 51-item
      National Eye Institute-Visual Functioning Questionnaire. The similarity of
      problems mentioned across refractive error type and correction method suggests it
      will be possible to develop a single questionnaire with adequate content validity
      to compare the impact of different modes of correction in vision-targeted, health
      related quality of life.

PMID- 14644710
TI  - Psychometric properties of the National Eye Institute-Refractive Error Quality of
      Life instrument.
AB  - OBJECTIVE: To estimate the psychometric properties of a vision-targeted measure
      of health-related quality of life, the National Eye Institute-Refractive Error
      Quality of Life survey (NEI-RQL), which includes 13 scales designed to assess the
      impact of refractive error and its correction on day-to-day life. DESIGN: Cross
      sectional survey. PARTICIPANTS: The NEI-RQL was self-administered by 667 myopes,
      380 hyperopes, and 114 emmetropes recruited from the practices of 6 medical
      centers. All participants had near and distance visual acuity of 20/32 or better
      in the worse eye while benefiting from their current method for correction of
      refractive error (glasses, contact lens, refractive surgery). METHODS: Mean
      scores, standard deviations, internal consistency reliability, and test-retest
      intraclass correlations were estimated for the NEI-RQL scales. Item
      discrimination was assessed by item-scale correlations. Construct validity was
      evaluated by assessing the sensitivity of scale scores to type of refractive
      error, type of refractive error correction, and spherical equivalent. Construct
      validity of the NEI-RQL was compared to those of the Medical Outcomes Study 36
      item short-form health survey (SF-36) and the National Eye Institute Vision
      Functioning Questionnaire (NEI VFQ-25) in a random subsample of respondents. MAIN
      OUTCOME MEASURES: The 13 NEI-RQL scales-clarity of vision, expectations, near
      vision, far vision, diurnal fluctuations, activity limitations, glare, symptoms,
      dependence on correction, worry, suboptimal correction, appearance, and
      satisfaction with correction. RESULTS: Emmetropes tended to score significantly
      better on the NEI-RQL scales than myopes and hyperopes. The method of refractive
      error correction was also associated with NEI-RQL scores. In addition, the NEI
      RQL multi-item scales accounted for 29% of the variance in the NEI-RQL
      satisfaction with correction item beyond that explained by the SF-36 and the NEI
      VFQ-25. CONCLUSION: These results support the reliability and construct validity
      of the NEI-RQL. The instrument appears to be useful for comparisons of people
      with different types of correction for refractive error.

PMID- 14644711
TI  - Responsiveness of the National Eye Institute Refractive Error Quality of Life
      instrument to surgical correction of refractive error.
AB  - OBJECTIVE: Refractive error and the means by which it is corrected may impact
      substantially on quality of vision and health-related quality of life in ways not
      captured adequately by standard measures of visual acuity. The goal of this
      analysis was to evaluate the responsiveness of the National Eye Institute
      Refractive Error Quality of Life (NEI-RQL) instrument to surgical correction of
      refractive error. DESIGN: Prospective, multicenter cohort study. PARTICIPANTS:
      The NEI-RQL, a 42-item measure with 13 scales, was self-administered by 185
      patients before and after undergoing surgical correction of myopic or hyperopic
      refractive error. Preoperative and postoperative clinical information was
      collected, including refractive error and corrected visual acuity. METHODS:
      Differences between preoperative and postoperative NEI-RQL scores were examined.
      Responsiveness was assessed using the standardized response mean and the
      responsiveness statistic. We also compared scales using relative efficiency
      estimates. MAIN OUTCOME MEASURES: Changes in NEI-RQL scales (clarity of vision,
      expectations, near vision, far vision, diurnal fluctuations, activity
      limitations, glare, symptoms, dependence on correction, worry, suboptimal
      correction, appearance, and satisfaction with correction). RESULTS: For myopes
      and hyperopes combined, refractive surgical correction was associated with
      statistically significant (P<0.05) improvements in scores for 11 of 13 scales.
      The largest improvements, ranging from 26 to 58 points on the 0 to 100 possible
      score range, were seen in expectations, activity limitations, dependence on
      correction, appearance, and satisfaction with correction. Separate analysis of
      myopes and hyperopes revealed similar effects in the 2 groups. Baseline scores
      were found to be predictive of change after surgery. CONCLUSIONS: The NEI-RQL is
      responsive to changes in vision-targeted health-related quality of life resulting
      from keratorefractive surgery. This instrument may prove useful for evaluating
      the beneficial and adverse impacts of surgical and nonsurgical methods of
      refractive error correction.

PMID- 14644712
TI  - Cost-utility analysis of cataract surgery in the second eye.
AB  - OBJECTIVE: To perform a reference case cost-utility analysis of second-eye
      cataract surgery by using the current literature on cataract outcomes and
      complications. DESIGN: Computer-based econometric modeling. METHODS: Visual
      acuity data of patients treated and observed over a 4-month postoperative period
      were obtained from the U.S. National Cataract Patient Outcomes Research Team
      report. The results from this prospective study were combined with those of other
      studies that investigated the complication rates of cataract surgery to complete
      the cohort of patients and outcomes. These synthesized data were incorporated
      with time trade-off utility values, which accounted for prior successful cataract
      surgery in the fellow eye. Cost-utility determinations were made with decision
      analysis, and present value modeling was used to account for the time value of
      money and health state consequences. MAIN OUTCOME MEASURES: The number of quality
      adjusted life-years (QALYs) gained was calculated for the study group undergoing
      second-eye cataract surgery, assuming that the postoperative vision in the second
      eye was equivalent to the vision in the first eye after surgery (20/27). This was
      divided into the cost of the procedure to find the number of year 2001 nominal
      U.S. dollars spent per QALY gained. RESULTS: Second-eye cataract surgery, as
      compared with unilateral pseudophakia, resulted in a mean gain of 1.31
      undiscounted QALYs per patient treated. A 3% annual discount rate, dependent on
      the duration of benefit, was used, yielding 0.92 discounted QALYs gained over a
      12-year life expectancy. The mean discounted cost of treatment for each patient
      totaled 2509 US dollars. The cost divided by the QALYs gained (benefit) resulted
      in 2727 US dollars per QALY gained for this procedure. Sensitivity analysis
      varying costs and utility values revealed a range from 2045 US dollars to 3649 US
      dollars per QALY gained. CONCLUSIONS: Second-eye cataract surgery is an extremely
      cost-effective procedure when compared with other interventions across medical
      specialties. The cost-effectiveness of second-eye surgery diminishes only
      slightly from the 2023 US dollars per QALY gained from first-eye cataract
      surgery. This suggests that patients with good vision in one eye and visual loss
      from cataract in the fellow eye derive substantial benefit from cataract
      extraction.

PMID- 14644713
TI  - Associations of cataract with antioxidant enzymes and other risk factors: the
      French Age-Related Eye Diseases (POLA) Prospective Study.
AB  - PURPOSE: To determine the association of potential risk factors, including
      antioxidant enzymes, with the incidence of cataract. DESIGN: Cohort study.
      PARTICIPANTS: At baseline, the Age-Related Eye Diseases (Pathologies Oculaires
      Liees a l'Age, POLA) Study included 2584 residents of Sete (southern France) aged
      60 years or older. From September 1998 to May 2000, a 3-year follow-up
      examination was performed on 1947 of the 2436 surviving participants (79.9%).
      METHODS: Cataract classification was based on a standardized lens examination at
      the slit lamp, according to Lens Opacities Classification System III. Biologic
      measurements were performed at baseline from fasting blood samples. MAIN OUTCOME
      MEASURES: At baseline and follow-up, the presence of cataract was defined as: NC
      or nuclear opalescence (NO) > or = 4 for nuclear cataract, C > or = 4 for
      cortical cataract, and P > or = 2 for posterior cataract (PSC) opacities, using
      opacity grades corrected for interobserver variability. Incidence rates were
      assessed separately for right and left eyes and for each type of cataract.
      RESULTS: In the multivariate model, the incidence of cortical cataract was
      increased in subjects with high red blood cell superoxide dismutase activity
      (odds ratio [OR] 4.2 [1.5-12.1], P = 0.007). The incidence of PSC cataract was
      increased in subjects with a high level of plasma glutathione peroxidase (OR 1.8
      [1.0-3.3], P = 0.05). In addition to age, gender, and opacities at baseline,
      significant risk factors for incident cataract were: long-duration diabetes (OR
      5.8, P = 0.001 for cortical cataract) and lifetime heavy smoking (OR 2.9, P =
      0.006 for PSC cataract). CONCLUSIONS: Consistent with the baseline analysis, the
      results of this prospective study suggest that antioxidant enzymes might be
      implicated in the etiology of cataract.

PMID- 14644714
TI  - Comparison of adverse events with daily disposable hydrogels and spectacle wear:
      results from a 12-month prospective clinical trial.
AB  - OBJECTIVE: To evaluate the type and incidence of adverse events seen with daily
      disposable hydrogel contact lens wear compared with a control (spectacle) group
      over 12 months. DESIGN: Prospective, randomized, observer-masked, comparative
      clinical trial. PARTICIPANTS: Two hundred eighty-one myopes with no prior contact
      lens wear experience were enrolled from August to December 1996. Subjects were 16
      to 35 years old and had refractive errors ranging from a -0.75-diopter (D) sphere
      to a -6.00-D sphere with a cylinder less than -1.00 D. INTERVENTION: Each subject
      was randomly assigned to wear either bilateral disposable hydrogels on a daily
      disposable wear schedule or spectacles. MAIN OUTCOME MEASURE: Type and incidence
      of adverse events from each group. Adverse events were categorized as serious,
      significant, and nonsignificant based on the potential to cause vision
      impairment, severity at event, and level of clinical concern. RESULTS: At
      baseline, 1.6% of eyes had asymptomatic infiltrates that were nonsignificant.
      During the study, asymptomatic infiltrates were seen in both contact lens and
      spectacle groups at 20.5 events versus 11.3 events per 100 eyes per year of wear.
      No significant events were seen with the spectacle group. With the contact lens
      group, the type and incidence of significant events per 100 eyes per year of lens
      wear were corneal peripheral ulcer, 2.5 events; infiltrative keratitis, 1.5
      events; and papillary conjunctivitis, 1 event. The incidence of both significant
      and nonsignificant events was greater with the contact lens group (P<0.05). No
      serious events (i.e., microbial keratitis) were seen in either group. A greater
      number of subjects were lost to follow-up or permanently discontinued from the
      contact lens group relative to the spectacle group (33% vs. 17%, P = 0.002). Lens
      related problems such as dryness, discomfort, and difficulty with insertion and
      removal accounted for 27% of discontinuations from the contact lens group. Poor
      compliance (40%) was the greatest reason for discontinuations from the spectacle
      group. CONCLUSIONS: No clinically serious events were seen with either group.
      Only a small percentage of contact lens-wearing eyes presented with significant
      events, which is promising for daily disposable lens wear. Far more contact lens
      subjects were lost to follow-up or discontinued. Small, asymptomatic,
      subepithelial corneal infiltrates of unknown significance were seen in both
      contact lens- and spectacle-wearing eyes.

PMID- 14644715
TI  - Postoperative inflammation after implantation of the implantable contact lens.
AB  - PURPOSE: To evaluate postoperative inflammation after implantation of the
      implantable contact lens (ICL) to treat moderate to high myopia. DESIGN:
      Noncomparative, prospective case series. PARTICIPANTS: Five hundred twenty-five
      eyes of 293 patients with between 3 and 20 diopters of myopia participating in
      the United States Food and Drug Administration clinical trial of the ICL for
      myopia. INTERVENTION: Implantation of the ICL. MAIN OUTCOME MEASURES: Clinical
      assessments of anterior chamber flare and cellular reaction for up to 3 years
      after surgery and laser flare-cell meter measurements for up to 2 years after
      surgery. RESULTS: Clinical flare and cellular reaction was reported as absent in
      99.6% to 100% of cases and in no case demonstrated more than trace reaction at
      all postoperative visits 1 month or more after surgery. In a small subset of the
      study participants who were tested with the laser flare and cell meter,
      measurements taken between 3 months and 3 years after surgery were within the
      normal range. CONCLUSIONS: The implantation of the ICL does not cause a long-term
      (2-3 years) inflammatory response within the eye.

PMID- 14644716
TI  - Dynamic morphology of clear corneal cataract incisions.
AB  - OBJECTIVE: Clear corneal cataract incisions without sutures allow for rapid
      visual rehabilitation after phacoemulsification but might be associated with an
      increased risk of postoperative infection. The goal of this study was to examine
      in vitro dynamic changes in unhealed clear corneal cataract incisions that might
      adversely affect the risk of intraocular infection. DESIGN: Laboratory
      investigation. METHODS: Self-sealing clear corneal incisions were created in
      cadaveric human and rabbit eyes, and intraocular pressure was controlled with an
      infusion cannula. Incisions were imaged in real time using optical coherence
      tomography as intraocular pressure was varied. Using an artificial anterior
      chamber, India ink was applied to the surface of cadaveric human corneas with
      clear corneal incisions to detect possible flow of surface fluid along the
      incision. Intraocular pressure was varied by raising and lowering the infusion
      bottle so as to simulate the variation in intraocular pressure that would occur
      with successive blinks. RESULTS: Optical coherence tomography demonstrated
      variation of corneal wound morphology in response to changes in intraocular
      pressure. Higher intraocular pressures were associated with close apposition of
      the wound edges, with no tendency for wound leakage. At low intraocular
      pressures, however, wound edges tended to gape, starting at the internal aspect
      of the wound. One incision opened along the entire length, allowing fluid flow
      across the cornea. Histologic examination revealed India ink particles in all
      incisions for up to three fourths of the length of the wound. CONCLUSIONS:
      Transient reduction of intraocular pressure might result in poor wound apposition
      in clear corneal incisions, with the potential for fluid flow across the cornea
      and into the anterior chamber, with the attendant risk of endophthalmitis.

PMID- 14644717
TI  - Clear lens extraction for the correction of high myopia.
AB  - OBJECTIVE: To evaluate the postoperative outcomes and intraoperative and
      postoperative complications of clear lens extraction (CLE) with posterior chamber
      intraocular lens (IOL) implantation in highly myopic eyes. DESIGN: Retrospective
      case series. PARTICIPANTS: One hundred seven patients (190 eyes) who had
      undergone CLE with posterior chamber IOL implantation and who had been observed
      for at least 3 years after surgery. METHODS: Medical records of patients who had
      undergone CLE with posterior chamber IOL implantation to treat high myopia (axial
      length >26.00 mm) over 7 years (January 1990 to December 1996) were reviewed.
      Visual acuity and refractive error were assessed before and after surgery, and
      perioperative, intraoperative, and postoperative complications were recorded.
      MAIN OUTCOME MEASURES: Axial length, preoperative and final best spectacle
      corrected visual acuity (BSCVA), preoperative and postoperative spherical
      equivalent (SE), argon laser treatments, surgical complications,
      neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy, retinal detachment
      (RD), time from surgery or Nd:YAG capsulotomy to RD, subfoveal choroidal
      neovascularization (CNV), and follow-up period. RESULTS: The mean postoperative
      follow-up period was 4.78 years (range, 3.10-8.03 years). Final BSCVA was better
      than preoperative BSCVA in 159 eyes (83.68%), equal in 24 eyes (12.63%), and
      worse in 7 eyes (3.68%). Postoperative BSCVA was 20/40 or better in 136 eyes
      (71.60%) vs. 52 eyes (27.36%) before surgery (P<0.001). The mean final
      postoperative SE was -1.22 diopters. The risk of Nd:YAG laser capsulotomy was
      77.89%. The incidence of RD was 2.10%; retinal reattachment was achieved in all
      cases, and none of these eyes had worse final BSCVA than before surgery.
      Subfoveal CNV developed in 4 eyes (2.10%) of 3 patients; all of these eyes
      presented with a macular lacquer crack. CONCLUSIONS: Clear lens extraction with
      posterior chamber IOL implantation has good outcomes with acceptable
      predictability and improvement in best-corrected visual acuity. During follow-up,
      patients tended to remain stable, and the risk of retinal detachment was low. We
      attribute our favorable results to careful patient selection and follow-up.

PMID- 14644718
TI  - Cataract surgery as a risk factor for retinal detachment in very highly myopic
      eyes.
AB  - PURPOSE: To evaluate the incidence of retinal detachment (RD) after cataract
      surgery performed by phacoemulsification in very highly myopic eyes. DESIGN:
      Retrospective, paired-eye, case-control trial. PARTICIPANTS AND INTERVENTION: We
      assessed the development of RD in 930 eyes from 930 subjects (mean age = 62.5 +/-
      8.5 years) affected by very high myopia (between -15 and -30 diopters) undergoing
      cataract surgery after uncomplicated phacoemulsification (cataract-subjected [CS]
      eyes). Fellow eyes served as controls. Follow-up was 36 months. MAIN OUTCOME
      MEASURE: Detachment of the retina. RESULTS: Retinal detachment was observed in
      8.0% of CS eyes compared with 1.2% of control eyes (P<0.01, chi-square test). In
      CS eyes, posterior RD was most common (52.7% of eyes with RD). In control eyes,
      peripheral detachments with or without macular involvement were most common
      (47.3% of eyes with RD). CONCLUSION: Cataract surgery, despite the use of a safe
      technique such as phacoemulsification, increases the risk of RD development in
      very highly myopic eyes.

PMID- 14644719
TI  - A 3-month randomized controlled trial of bimatoprost (LUMIGAN) versus combined
      timolol and dorzolamide (Cosopt) in patients with glaucoma or ocular
      hypertension.
AB  - PURPOSE: To compare the efficacy and safety of topical bimatoprost (LUMIGAN;
      Allergan, Inc., Irvine, CA) once daily with that of topical combined timolol and
      dorzolamide (Cosopt; Merck and Co, Inc., Whitehouse Station, NJ) twice daily.
      DESIGN: Prospective, randomized, double-masked, multicenter clinical trial.
      PARTICIPANTS: One hundred seventy-seven patients with a diagnosis of glaucoma or
      ocular hypertension and inadequate control of intraocular pressure (IOP) after at
      least 2 weeks of topical timolol maleate 0.5% monotherapy. METHODS: Patients were
      randomized to receive bimatoprost 0.03% once daily (n = 90) or combined timolol
      0.5% and dorzolamide 2% twice daily (n = 87) over a 3-month period. MAIN OUTCOME
      MEASURES: Intraocular pressure, the primary end point, was measured at 8 AM and
      10 AM at baseline, week 1, and months 1, 2, and 3, and also at 4 PM and 8 PM at
      baseline and month 3. RESULTS: Bimatoprost provided significantly greater IOP
      lowering compared with combined timolol and dorzolamide. At the 8 AM
      measurements, bimatoprost lowered mean IOP 6.8 mmHg to 7.6 mmHg from baseline,
      whereas combined timolol and dorzolamide lowered mean IOP 4.4 to 5.0 mmHg from
      baseline (P<0.001). At the last follow-up, patients had better diurnal IOP
      control with bimatoprost than combined timolol and dorzolamide. At 8 AM at the 3
      month visit, the percentages of patients achieving IOPs of <or =13 mmHg, < or =14
      mmHg, < or =15 mmHg, or < or =16 mmHg were more than twice as high for
      bimatoprost than for combined timolol and dorzolamide (all P< or =0.008). Taste
      perversion, ocular burning, and stinging with instillation were more common with
      combined timolol and dorzolamide, whereas conjunctival hyperemia was more common
      with bimatoprost. CONCLUSIONS: In individuals with glaucoma or ocular
      hypertension, uncontrolled on a topical beta-blocker alone, bimatoprost lowered
      IOP more consistently than did combined timolol and dorzolamide.

PMID- 14644720
TI  - Intravenous pulse methylprednisolone therapy in eye disease: effect on glucose
      tolerance.
AB  - PURPOSE: To determine which subjects need close glycemic monitoring during
      intravenous pulse methylprednisolone therapy for eye disease. DESIGN:
      Retrospective study in a national eye center. PARTICIPANTS: Two hundred twenty
      four subjects who received over a one-year period 250 to 1000 mg daily
      intravenous methylprednisolone over 3 consecutive days for ophthalmologic
      conditions. METHODS: Blood glucose monitoring during pulse methylprednisolone
      therapy followed a protocol written in 1995. We analyzed the effects of 3 days of
      pulse methylprednisolone therapy on glucose tolerance and their clinical
      implications in diabetic and nondiabetic subjects treated during 2000. MAIN
      OUTCOME MEASURE: Serial morning fasting blood glucose; that is, before the first
      pulse and the day after each pulse, blood glucose self-monitoring for diabetic
      subjects and specific hypoglycemic drug interventions were recorded. RESULTS: All
      subjects showed a median 50% increase in fasting glucose after the first steroid
      infusion, without a significant difference between diabetic and nondiabetic
      subjects. Thereafter, the 196 nondiabetic subjects showed spontaneous decreases
      of their fasting glucose toward baseline values despite the following infusions,
      whereas the 28 diabetic subjects (all type 2) demonstrated further increases of
      blood glucose, and 7 received rapid-release insulin to maintain blood glucose
      lower than 14 mmol/l. All 5 diabetic subjects with baseline glycosylated
      hemoglobin >/==" BORDER="0"> 8.3% required insulin therapy. CONCLUSIONS: Close
      glycemic monitoring seems necessary only for subjects with diabetes during
      intravenous pulse methylprednisolone therapy for ophthalmologic conditions. The
      probability of subjects with type 2 diabetes requiring insulin during this
      therapy does seem to be positively related to the level of pretreatment
      glycosylated hemoglobin.

PMID- 14644721
TI  - Anecortave acetate as monotherapy for treatment of subfoveal neovascularization
      in age-related macular degeneration: twelve-month clinical outcomes.
AB  - PURPOSE: To evaluate safety and efficacy of the angiostatic agent anecortave
      acetate, compared with a placebo, for treatment of subfoveal choroidal
      neovascularization (CNV). DESIGN: Ongoing masked, randomized, placebo-controlled,
      parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a
      placebo. PARTICIPANTS: There were 128 eyes of 128 patients with subfoveal CNV
      secondary to age-related macular degeneration who were enrolled and treated, with
      80% (102/128) of eyes presenting with predominantly classic lesions at baseline.
      METHODS: All eyes received a posterior juxtascleral depot application of masked
      study medication or a placebo, with retreatment at 6-month intervals if the
      masked investigator believed the patient could benefit. Patients received
      periodic detailed ophthalmic examinations with both fluorescein and indocyanine
      green angiography, general physical examinations with electrocardiograms, and
      hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data
      were periodically reviewed by the Independent Safety Committee overseeing the
      study. MAIN OUTCOME MEASURES: Best-corrected logarithm of the minimum angle of
      resolution (logMAR) vision and fluorescein angiographic lesion characteristics
      were compared over time and among treatment groups. RESULTS: At month 12,
      anecortave acetate (15 mg) administered at 6-month intervals was statistically
      superior to the placebo for 3 measures of clinical efficacy: mean change from
      baseline vision (P = 0.0131), stabilization of vision (<3 logMAR line change; P =
      0.0323), and prevention of severe vision loss (decrease of > or = 6 logMAR lines
      from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions
      revealed that anecortave acetate (15 mg) was also superior to the placebo at 1
      year for each of these 3 measures of visual outcome (Ps = 0.0022, 0.0100, and
      0.0299, respectively). Anecortave acetate (15 mg) trended toward significance
      over the placebo at month 12 for inhibition of total lesion growth and for
      inhibition of both the total CNV component and the classic CNV component in both
      the overall and subgroup analyses. The Independent Safety Committee identified no
      clinically relevant treatment-related safety issues. CONCLUSIONS: Anecortave
      acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining
      vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion
      growth.

PMID- 14644723
TI  - Quantifying alterations of macular thickness before and after panretinal
      photocoagulation in patients with severe diabetic retinopathy and good vision.
AB  - PURPOSE: To investigate the alterations of macular thickness during and after
      panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy
      and good vision, and to compare the outcomes of weekly and biweekly treatments.
      DESIGN: Prospective, comparative interventional case series. PARTICIPANTS: Thirty
      six patients with severe nonproliferative diabetic retinopathy or non-high-risk
      proliferative diabetic retinopathy whose visual acuity was 20/20 or better before
      PRP. METHODS: Seventy-two eyes of 36 patients underwent scatter PRP in 4
      sessions. The macular thickness was measured by optical coherence tomography. The
      photocoagulation sessions were performed weekly to one eye and biweekly to the
      other eye. Each eye was selected at random. MAIN OUTCOME MEASURES: Best-corrected
      visual acuity and macular thickness. RESULTS: Visual acuities were maintained in
      89% of eyes with weekly treatments and 92% of eyes with biweekly treatments.
      Macular thickness was increased transiently in the central macula in both eyes,
      more in the weekly treated eyes, and then decreased to control levels in eyes
      treated biweekly but remained thickened in eyes treated weekly. CONCLUSION: For
      eyes with severe diabetic retinopathy and good vision, PRP with either weekly or
      biweekly treatment did not affect postoperative visual acuity. However, biweekly
      treatments allowed faster recovery of macular thickening after PRP than weekly
      treatments.

PMID- 14644724
TI  - Photodynamic therapy with verteporfin for subfoveal idiopathic choroidal
      neovascularization: one-year results from a prospective case series.
AB  - OBJECTIVE: To study the safety and efficacy of photodynamic therapy (PDT) with
      verteporfin in treating subfoveal choroidal neovascularization (CNV) of
      idiopathic cause. DESIGN: A prospective, noncomparative, consecutive, open-label,
      two-center, interventional case series. PARTICIPANTS: Patients aged 50 years or
      younger with the diagnosis of idiopathic CNV by exclusion of other related causes
      together with the CNV extending under the geometric center of the foveal
      avascular zone. METHODS: Seventeen eyes from 17 patients received PDT with
      verteporfin according to a standardized protocol. Retreatment was considered if
      fluorescein leakage from the CNV was shown in fluorescein angiography at every 3
      month follow-up. The visual, clinical, and angiographic responses were observed.
      Complications from treatment were monitored and documented. MAIN OUTCOMES
      MEASURES: The changes in the best-corrected visual acuity (BCVA) at the 1-year
      follow-up. The proportion of patients with improved (gained 2 lines or more),
      stable, and dropped (lost 2 lines or more) vision and the mean number of
      treatments required during the 1-year interval were measured. Complications were
      monitored and tabulated. RESULTS: Seventeen eyes with complete 1-year follow-up
      were analyzed. The mean logarithm of the minimum angle of resolution BCVA
      improved from 0.64 to 0.41 (Wilcoxon signed-ranks test, P = 0.007). Sixteen eyes
      (94%) had stable or improved vision. Only one patient (6%) had moderate loss of
      vision. The mean number of PDT treatment was 1.8 per eye over the 1-year period.
      Patients with smaller lesion size or active vascular CNV on presentation were
      more likely to have a final BCVA of 20/100 or better (Fisher's exact test, P =
      0.006 and P = 0.015, respectively). No serious local or systemic complications
      were encountered. CONCLUSIONS: PDT seems to be a promising treatment strategy in
      achieving a stable or improved vision for subfoveal idiopathic CNV. The treatment
      was well tolerated. Further studies and longer follow-up are warranted to assess
      the long-term safety and efficacy of PDT compared with observation or other
      treatment modalities.

PMID- 14644725
TI  - Morphologic and angiographic assessment of the macula after macular translocation
      surgery with 360 degrees retinotomy.
AB  - PURPOSE: To compare the optical coherence tomographic assessment of retinal
      thickness and the fluorescein angiographic appearance after macular translocation
      surgery for subfoveal choroidal neovascularization. DESIGN: Retrospective,
      noncomparative, interventional case series. PARTICIPANTS: Twenty-three
      consecutive eyes. INTERVENTION AND TESTING: Optical coherence tomography and
      fluorescein angiography were performed before and 6 to 15 months (mean +/-
      standard error [SE], 10.4+/-0.7) after macular translocation surgery with a 360
      degrees retinotomy in 23 patients, ages 48 to 79 years, with age-related macular
      degeneration (12 eyes), polypoidal choroidal vasculopathy (2 eyes), and high
      myopia (9 eyes). The diameter of the choroidal neovascularizations ranged from
      0.3 to 2.6 disc diameters (mean +/- SE, 1.2+/-0.2), and the angle of rotation of
      the retina ranged from 11 degrees to 45 degrees (mean +/- SE, 29.1+/-2.1 degrees
      ). RESULTS: The preoperative best-corrected visual acuity ranged from hand
      motions to 20/100, and the postoperative best-corrected visual acuity ranged from
      20/667 to 20/25. Optical coherence tomography demonstrated a concave foveal
      configuration after surgery in all 23 eyes, with a mean foveal thickness of 150+/
      11 micro m (mean +/- SE). Fluorescein angiography showed various degrees of
      fluorescein leakage with a pattern similar to cystoid macular edema in 16 of 23
      eyes (70%). CONCLUSIONS: The newly located macula after macular translocation
      surgery with a 360 degrees retinotomy had cystoid macular edema on fluorescein
      angiography and normal macular configuration with normal thickness in optical
      coherence tomography.

PMID- 14644726
TI  - Trypan blue staining in vitreoretinal surgery.
AB  - PURPOSE: To evaluate the efficacy of trypan blue for staining the internal
      limiting membrane (ILM) and epiretinal membranes (ERM) in vitreoretinal surgery.
      DESIGN: Prospective noncomparative case series. PARTICIPANTS: Fifty eyes of 50
      patients with macular pucker (n = 22), macular hole (n = 18), or a combination (n
      = 2), proliferative vitreoretinopathy (n = 5), or diabetic retinopathy (n = 3).
      METHODS: Trypan blue 0.2% was used to stain the ILM or ERM during vitreoretinal
      surgery. MAIN OUTCOME MEASURES: The intraoperative visibility of the membranes
      was scored as poor, moderate, good, or excellent. RESULTS: The application of
      trypan blue onto the ILM or the ERM resulted in a useful bluish staining,
      facilitating the identification, delineation, and removal of the membranes in all
      surgeries. No residual staining or adverse effects related to the dye were
      observed. CONCLUSIONS: Trypan blue stains both ILM and ERM and might be an useful
      tool in vitreoretinal surgery.

PMID- 14644727
TI  - Incidence and epidemiological characteristics of rhegmatogenous retinal
      detachment in Beijing, China.
AB  - OBJECTIVE: To estimate the incidence and epidemiologic characteristics of
      rhegmatogenous retinal detachment (RRD) in Beijing, China. DESIGN: Prospective
      population-based incidence study. PARTICIPANTS: The population of Beijing and its
      nearby suburbs (N = 6 589 000). MAIN OUTCOME MEASURE: Incident RRD. RESULTS: A
      total of 526 patients with RRD were newly diagnosed between October 1999 and
      September 2000. The annual incidence was 7.98/100 000 people (95% confidence
      interval = 7.30-8.67). People aged 60 to 69 had the highest incidence (22.15/100
      000). Incidences of 3 subtypes of RRD were 0.93/100 000 for related to blunt
      trauma, 0.80/100 000 for aphakic and pseudophakic, and 6.25/100 000 for
      nontraumatic phakic retinal detachment. A significantly higher incidence was
      found in males for traumatic detachment, but not for the other 2 subtypes of RRD.
      High myopia (> or = -6 diopters) was more prevalent in bilateral RRD (57.1%) than
      in the unilaterally affected patients (32.4%). CONCLUSIONS: The incidence of RRD
      in Beijing is comparable to most of the reports from the developed countries. It
      is estimated that there are 9000 to 10 000 new cases of RRD in China each year.
      As 60% to 70% of the RRD patients live in small towns or remote farming areas
      with limited access to qualified retina-vitreous surgeons, care for these
      patients presents a great challenge in China.

PMID- 14644728
TI  - Snowflake vitreoretinal degeneration: follow-up of the original family.
AB  - PURPOSE: The ocular findings, systemic features, and genetic loci distinguishing
      known genetic causes of vitreoretinal degenerations were studied in the original
      Snowflake family. DESIGN: Prospective, comparative study and molecular genetic
      investigation. PARTICIPANTS: Members of the original snowflake vitreoretinal
      degeneration family. METHODS: Clinical data were collected on 26 family members
      by history and examination. Thirteen of the 26 total family members underwent
      prospective examination. Linkage to known vitreoretinal degeneration loci
      (COL2A1, COL11A1, and the Wagner disease locus) was evaluated with short tandem
      repeat markers. MAIN OUTCOME MEASURES: Ocular and systemic features of known
      vitreoretinal degenerations. RESULTS: Six of the 13 prospectively examined
      subjects had snowflake vitreoretinal degeneration. Corneal guttae (4/5; 80%),
      early onset cataract (5/6; 83%), fibrillar vitreous degeneration (6/6; 100%), and
      peripheral retinal abnormalities (5/6; 83%), including minute crystallinelike
      deposits called snowflakes (4/6; 67%), were common. Retinal detachment was seen
      in 1 of 6 of these prospectively examined subjects (17%). A total of 14 affected
      subjects were identified within the family, and in 3 (21%), retinal detachment
      developed. Orofacial features, early-onset hearing loss, and arthritis typical of
      Stickler syndrome were absent. Linkage to known vitreoretinal degeneration loci
      was excluded. CONCLUSIONS: The absence of vitreous gel in the retrolental space
      and presence of fibrillar vitreous degeneration were consistent with the vitreous
      structure reported for collagen 11A1 (COL11A1) but not collagen 2A1 (COL2A1)
      mutations. The absence of systemic features was characteristic of the
      vitreoretinopathies linked to chromosome 5q13 (Wagner disease and erosive
      vitreoretinopathy) and mutations in exon 2 of the COL2A1 gene. Snowflakes in the
      peripheral retina and the absence of nyctalopia, posterior chorioretinal atrophy,
      and tractional retinal detachment were inconsistent with the chromosome 5q13
      vitreoretinopathies. The association of Fuchs' corneal endothelial dystrophy
      found in this family has not been reported previously in other vitreoretinal
      degenerations. These findings and the exclusion of known genetic loci suggest
      snowflake is a distinct vitreoretinal degeneration.

PMID- 14644730
TI  - Sutureless vitrectomy surgery.

PMID- 14644731
TI  - Sutureless virectomy surgery.

PMID- 14644732
TI  - Sutureless vitrectomy surgery.

PMID- 14644734
TI  - Lidocaine gel versus drops.

PMID- 14644737
TI  - Preoperative ofloxacin.

PMID- 14644739
TI  - Ladarvision excimer laser.

PMID- 14644740
TI  - Helicobacter pylori and glaucoma.

PMID- 14644742
TI  - Evaluation of the lacrimal sac.

PMID- 14644746
TI  - Choroidal folds and optic neuropathy.

PMID- 14644747
TI  - Antidiuretic hormone resistance in the neonatal cortical collecting tubule is
      mediated in part by elevated phosphodiesterase activity.
AB  - Neonates cannot concentrate their urine to the same degree as adults. One of the
      key factors in concentrating the urine is the renal collecting duct osmotic water
      permeability (Pf) response to antidiuretic hormone (ADH). Neonatal cortical
      collecting ducts have a blunted Pf response to ADH compared with adult tubules
      (Pf: 119.0 +/- 12.5 vs. 260.1 +/- 29.5 microm/s, P < 0.05). We found that the
      phosphodiesterase activity in the neonatal collecting ducts was higher than that
      in the adult collecting ducts (3,970 +/- 510 vs. 2,440 +/- 220 cpm.microg tubular
      protein-1.20 min-1, P < 0.05). After pretreatment of in vitro microperfused
      tubules with the nonspecific phosphodiesterase inhibitor IBMX (10-6 M in the
      bath), the Pf response to ADH in neonatal collecting ducts was 271.4 +/- 51.7
      microm/s, which was identical to that of the adult collecting duct [315.3 +/-
      31.3 microm/s, P = not significant (NS)]. Rolipram, a specific type IV
      phosphodiesterase inhibitor, lowered the elevated phosphodiesterase activity in
      the neonatal tubules to that in the adult tubules (2,460 +/- 210 vs. 2,160 +/-
      230 cpm.microg tubular protein-1.20 min-1, P = NS). Neonatal tubules pretreated
      with rolipram (10-5 M) in the bath also had a Pf response to ADH that was
      comparable to that of the adult tubules (258.2 +/- 17.0 vs. 271.4 +/- 32.6
      microm/s, P = NS). Thus the elevated phosphodiesterase activity in the neonatal
      tubules appears to be due to an increase in type IV phosphodiesterase activity.
      Hence, one of the key factors in the decreased ability of neonates to concentrate
      their urine is overactivity of phosphodiesterase in the cortical collecting duct
      that blunts the neonatal collecting duct Pf response to ADH.

PMID- 14644748
TI  - Signaling cascade of ANG II-induced inhibition of alpha-MG uptake in renal
      proximal tubule cells.
AB  - ANG II and Na+-glucose cotransporter have been reported to be associated with the
      onset of diverse renal diseases. However, the effect of ANG II on Na+-glucose
      cotransporter activity was not elucidated. The effects of ANG II on alpha-methyl
      D-[14C]glucopyranoside (alpha-MG) uptake and its related signal pathways were
      examined in the primary cultured rabbit renal proximal tubule cells (PTCs). ANG
      II (>2 h; >10(-9) M) inhibited alpha-MG uptake in a time- and concentration
      dependent manner and decreased the protein level of Na+-glucose cotransporters,
      the expression of which was abrogated by both actinomycin D and cycloheximide
      exposure. ANG II-induced inhibition of alpha-MG uptake was blocked by losartan,
      an ANG II type 1 (AT1) receptor blocker, but not by PD-123319, an ANG II type 2
      receptor blocker. ANG II-induced inhibition of alpha-MG uptake was blocked by
      genistein, herbimycin A [tyrosine kinase (TK) inhibitors], mepacrine, and AACOCF3
      (phospholipase A2 inhibitors), suggesting the role of TK phosphorylation and
      arachidonic acid (AA). Indeed, ANG II increased AA release, which was blocked by
      losartan or TK inhibitors. The effects of ANG II on AA release and alpha-MG
      uptake also were abolished by staurosporine and bisindolylmaleimide I (protein
      kinase C inhibitors) or PD-98059 (p44/42 MAPK inhibitor), but not SB-203580 (p38
      MAPK inhibitor), respectively. Indeed, ANG II increased p44/42 MAPK activity. ANG
      II-induced activation of p44/42 MAPK was blocked by staurosporine. In conclusion,
      ANG II inhibited alpha-MG uptake via PKC-MAPK-cPLA2 signal cascade through the
      AT1 receptor in the PTCs.

PMID- 14644749
TI  - Thyroid hormone modulates rabbit proximal straight tubule paracellular
      permeability.
AB  - Proximal straight tubules (PST) from both neonatal and hypothyroid adult rabbits
      have a lower rate of passive volume absorption when perfused with a high-chloride
      solution simulating late proximal tubular fluid than adult rabbit PST. We
      hypothesized that the maturational increase in serum thyroid hormone levels
      mediates the developmental changes in PST paracellular permeability. Neonatal
      tubules had lower chloride permeability, higher transepithelial resistance, but
      comparable mannitol permeability compared with adult PST. The present in vitro
      microperfusion study directly examined whether thyroid hormone affects passive
      solute flux and whether thyroid hormone could explain the developmental changes
      in PST paracellular permeability. Passive chloride transport was 62.1 +/- 4.5,
      23.1 +/- 7.7, and 111.6 +/- 5.6 pmol.mm(-1).min(-1) in PST from euthyroid,
      hypothyroid, and hypothyroid animals that received thyroid treatment,
      respectively (control different from hypothyroid and thyroid treatment at P <
      0.05). This was due to a thyroid hormone-mediated change in chloride permeability
      (P(Cl)). Mannitol permeability was 3.65 + 1.03, -0.19 + 0.72, and 3.60 + 1.12 x
      10(-6) cm/s in PST from euthyroid animals, hypothyroid animals, and hypothyroid
      rabbits that received thyroid replacement, respectively (P < 0.05 hypothyroid vs.
      euthyroid and thyroid replacement). We demonstrate that PST from hypothyroid
      animals have a higher passive P(Na)/P(Cl) and P(HCO3)/P(Cl) than euthyroid
      controls. Finally, we examined whether these changes in permeability were
      paralleled by a change in PST paracellular resistance. Resistance was measured by
      current injection and cable analysis. The resistance in PST from hypothyroid
      rabbits was 6.3 +/- 0.8 Omega.cm(2), which was not different from control of 4.8
      +/- 0.7 Omega.cm(2), or 7.0 +/- 0.7 Omega.cm(2) in hypothyroid animals that
      received thyroid replacement. Therefore, the maturational increase in thyroid
      hormone levels does not fully explain the developmental changes in the
      paracellular pathway.

PMID- 14644750
TI  - The actin cytoskeleton facilitates complement-mediated activation of cytosolic
      phospholipase A2.
AB  - Cytosolic PLA(2)-alpha (cPLA(2)) and metabolites of arachidonic acid (AA) are key
      mediators of complement-dependent glomerular epithelial cell (GEC) injury.
      Assembly of C5b-9 increases cytosolic Ca(2+) concentration and results in
      transactivation of receptor tyrosine kinases and activation of PLC-gamma 1 and
      the 1,2-diacylglycerol (DAG)-PKC pathway. Ca(2+) and PKC are essential for
      membrane association and increased catalytic activity of cPLA(2). This study
      addresses the role of the actin cytoskeleton in cPLA(2) activation.
      Depolymerization of F-actin by cytochalasin D or latrunculin B reduced complement
      dependent [(3)H]AA release, as well as the complement-induced increase in cPLA(2)
      activity. These effects were due to inhibition of [(3)H]DAG production and PKC
      activation, implying interference with PLC. Complement-dependent [(3)H]AA release
      was also reduced by jasplakinolide, a compound that stabilizes F-actin and
      organizes actin filaments at the cell periphery, and calyculin A, which induces
      condensation of actin filaments at the plasma membrane. The latter drugs did not
      affect [(3)H]DAG production, suggesting their inhibitory actions were downstream
      of PKC. Neither cytochalasin D, latrunculin B, nor calyculin A affected
      association of cPLA(2) with microsomal membranes, and cytochalasin D and
      latrunculin B did not alter the localization of the endoplasmic reticulum. Stable
      transfection of constitutively active RhoA induced formation of stress fibers,
      stabilized F-actin, and attenuated the complement-induced increase in [(3)H]AA.
      Thus in GEC, cPLA(2) activation is dependent, in part, on actin remodeling. By
      regulating complement-mediated activation of cPLA(2), the actin cytoskeleton may
      contribute to the pathophysiology of GEC injury.

PMID- 14644751
TI  - Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal
      renal tubules and hOAT1 expressed in human kidney epithelial cells.
AB  - We recently showed that, in a proximal tubule cell line (opossum kidney cells),
      epithelial growth factor (EGF) stimulates basolateral organic anion transport
      (OAT) via ERK1/2, arachidonic acid, phospholipase A2, and generation of
      prostaglandins. PGE2 binds the prostanoid receptor and, thus, activates adenylate
      cyclase and PKA, which stimulate basolateral organic anion uptake. In the present
      study, we investigated whether this regulatory cascade is also true 1) for ex
      vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) in a
      human renal epithelial cell line stably expressing human OAT1 (IHKE-hOAT1). EGF
      activated ERK1/2 in S2 tubules and IHKE-hOAT1, and, in both cases, inhibition of
      ERK activation (by U-0126) abolished this stimulation. In S2 tubules and IHKE
      hOAT1, EGF led to an increase of organic anion uptake, which again was inhibited
      by U-0126. PGE2 stimulated basolateral organic anion uptake in rabbit S2 tubules
      and IHKE-hOAT1. EGF- and PGE2-mediated stimulation of organic anion uptake was
      abolished by inhibition of PKA in rabbit S2 tubules and IHKE-hOAT1, respectively.
      We conclude that 1) stimulation of basolateral organic anion uptake by EGF or
      PGE2 is a widespread (if not general) regulatory mechanism, 2) the signal
      transduction pathway involved seems to be general, 3) stimulation of basolateral
      organic anion uptake by EGF or PGE2 is also present under ex vivo conditions and,
      thus, is not a cell culture artifact, 4) activation of OAT1 is sufficient to
      explain the stimulatory effects of EGF and PGE2 in opossum kidney cells and
      rabbit S2 segments, and 5) stimulation of basolateral OAT1 by EGF or PGE2 is also
      important in humans and, thus, may have clinical implications.

PMID- 14644752
TI  - Differentiated human podocytes endogenously express an inhibitory isoform of
      vascular endothelial growth factor (VEGF165b) mRNA and protein.
AB  - Despite production by podocytes of the proangiogenic molecule vascular
      endothelial growth factor-A (VEGF), the glomeruli are not sites of angiogenesis.
      We recently described mRNA expression of an inhibitory splice variant of VEGF
      (VEGF165b) in normal kidney (Bates DO, Cui TG, Doughty JM, Winkler M, Sugiono M,
      Shields JD, Peat D, Gillatt D, and Harper SJ. Cancer Res 62: 4123-4131, 2002).
      Available anti-VEGF antibodies do not distinguish stimulatory from inhibitory
      VEGF families. To assess the production of VEGF165 (stimulatory) and VEGF165b
      (inhibitory) isoforms by human podocytes, we examined both primary cultured and
      conditionally immortalized human podocytes using family- and isoform-specific RT
      PCR. In addition, VEGF protein production was analyzed in podocytes, using
      isoform-specific double-strand small-interference RNAs (siRNA). RT-PCR
      demonstrated the production of VEGF189 mRNA by podocytes of both phenotypes. In
      contrast, on differentiation there was a splicing change from VEGF165 to VEGF165b
      mRNA. In addition, VEGF protein in the supernatant of conditionally immortalized,
      differentiated podocytes was reduced by VEGF165b siRNA to 20+/-11% of the level
      of mock-transfected cells (P < 0.01). No reduction was seen with mismatch siRNA.
      Moreover, there was no reduction in VEGF protein concentration in the supernatant
      of primary cultured, dedifferentiated human podocytes (109+/-8% of mismatch
      siRNA, P > 0.1). In conclusion, differentiated but not dedifferentiated human
      podocytes secrete significant amounts of VEGF165b protein. It is possible that
      this may explain the paradox of high VEGF production in the glomerulus but no
      angiogenesis. Furthermore, the existence of this splicing switch in relation to
      podocyte phenotype suggests that alternative splicing of the VEGF pre-RNA is a
      regulated process that is open to manipulation and therefore could be a target
      for novel cancer therapies.

PMID- 14644753
TI  - Central control of renal sodium-phosphate (NaPi-2) transporters.
AB  - Regulation of phosphate (Pi) reabsorption occurs through the up- and
      downregulation of the renal type-II sodium Pi cotransporters (NaPi-2). Recently,
      renal NaPi2-type expression has been identified in areas of the brain. The
      present study determined whether brain NaPi-2 is regulated by dietary Pi and
      whether the behavioral and renal adaptations to low-dietary Pi are controlled
      centrally. NaPi-2-like expression in the third ventricle (3V) and amygdala of
      juvenile Wistar rats was regulated by dietary Pi, as in the kidneys. When
      cerebrospinal fluid (CSF) Pi concentration was elevated by 3V injections of Pi in
      rats fed low-Pi diet (LPD), the behavioral and renal adaptations to LPD were
      abolished. Most importantly, NaPi-2 expression was markedly reduced not only in
      the brain, but also renal proximal tubules, despite the low plasma Pi milieu.
      This was confirmed by the significant reduction in the transport maximum for Pi
      (from 8.1+/-0.2 in LPD + veh 3V to 1.7+/-0.1 micromol Pi/ml glomerular filtration
      rate in LPD + 3V Pi, P < 0.001). These findings indicate that NaPi-2-like
      transporters in the brain are regulated by both dietary Pi and CSF Pi
      concentrations, and most significantly, that the central Pi milieu can regulate
      renal NaPi-2 expression. We hypothesize that central 3V NaPi-2 transporters may
      act as Pi sensors and help regulate both brain and whole body Pi homeostasis.

PMID- 14644754
TI  - Role of vasopressin in diabetes mellitus-induced changes in medullary transport
      proteins involved in urine concentration in Brattleboro rats.
AB  - In rats with streptozotocin-induced diabetes mellitus for 10-20 days, we showed
      that the abundance of the major medullary transport proteins involved in the
      urinary concentrating mechanism, urea transporter (UT-A1), aquaporin-2 (AQP2),
      and the Na+-K+-2Cl- cotransporter (NKCC2/BSC1), is increased, despite the ongoing
      osmotic diuresis. To test whether vasopressin is necessary for these diabetes
      mellitus-induced changes in UT-A1, AQP2, or NKCC2/BSC1, we studied Brattleboro
      rats because they lack vasopressin. Brattleboro rats were given vasopressin (2.4
      microg/day via osmotic minipump) for 5 or 12 days. At 5 days, vasopressin
      increased AQP2 protein abundance but decreased UT-A1 abundance compared with
      untreated Brattleboro rats. At 12 days, vasopressin increased the abundance of
      both UT-A1 and AQP2 proteins but did not alter NKCC2/BSC1. Next, untreated
      Brattleboro rats were made diabetic for 10 days by injecting them with
      streptozotocin (40 mg/kg). Diabetes mellitus increased the abundance of AQP2 and
      NKCC2/BSC1 proteins, but UT-A1 protein abundance did not increase. Third,
      vasopressin-treated Brattleboro rats were made diabetic with streptozotocin for
      10 days. In vasopressin-treated Brattleboro rats, diabetes mellitus increased UT
      A1, AQP2, and NKCC2/BSC1 protein abundances. Vasopressin significantly increased
      UT-A1 phosphorylation in vasopressin-treated diabetic Brattleboro rats but not in
      the other groups of Brattleboro rats. We conclude that 1) administering
      vasopressin to Brattleboro rats for 12 days, but not for 5 days, increases UT-A1
      protein abundance and 2) vasopressin is necessary for the increase in UT-A1
      protein in diabetic rats but is not necessary for the increase in AQP2 or NKCC2
      proteins.

PMID- 14644755
TI  - Differential control over postganglionic neurons in rat cardiac ganglia by NA and
      DmnX neurons: anatomical evidence.
AB  - In previous single-labeling experiments, we showed that neurons in the nucleus
      ambiguous (NA) and the dorsal moto nucleus of the vagus (DmnX) project to
      intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly
      in the size of their projection fields, axon caliber, and endings in cardiac
      ganglia. These differences in NA and DmnX axon cardiac projections raise the
      question as to whether they target the same, distinct, or overlapping populations
      of cardiac principal neurons. To address this issue, we examined vagal terminals
      in cardiac ganglia and trace injection sites in the brain stem using two
      different anterograde t ace s 1,1-dioleyl-3,3,3,3-tetramethylindocarbocyanine
      methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide]
      and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX
      neurons innervate the same cardiac ganglia, but these axons target separate
      subpopulations of principal neurons and 2) axons arising from neurons in the NA
      and DmnX in the contralateral sides of the brain stem enter the cardiac
      ganglionic plexus through separate bundles and preferentially innervate principal
      neurons near their entry regions, providing topographic mapping of vagal motor
      neurons in left and right brain stem vagal nuclei. Because the NA and DmnX
      project to distinct populations of cardiac principal neurons, we propose that
      they may play different roles in controlling cardiac function.

PMID- 14644756
TI  - Photoperiod differentially modulates photic and nonphotic phase response curves
      of hamsters.
AB  - Circadian pacemakers respond to light pulses with phase adjustments that allow
      for daily synchronization to 24-h light-dark cycles. In Syrian hamsters,
      Mesocricetus auratus, light-induced phase shifts are larger after entrainment to
      short daylengths (e.g., 10 h light:14 h dark) vs. long daylengths (e.g., 14 h
      light:10 h dark). The present study assessed whether photoperiodic modulation of
      phase resetting magnitude extends to nonphotic perturbations of the circadian
      rhythm and, if so, whether the relationship parallels that of photic responses.
      Male Syrian hamsters, entrained for 31 days to either short or long daylengths,
      were transferred to novel wheel running cages for 2 h at times spanning the
      entire circadian cycle. Phase shifts induced by this stimulus varied with the
      circadian time of exposure, but the amplitude of the resulting phase response
      curve was not markedly influenced by photoperiod. Previously reported
      photoperiodic effects on photic phase resetting were verified under the current
      paradigm using 15-min light pulses. Photoperiodic modulation of phase resetting
      magnitude is input specific and may reflect alterations in the transmission of
      photic stimuli.

PMID- 14644757
TI  - IL-1beta stimulates alveolar fluid absorption in fetal guinea pig lungs via the
      hypothalamus-pituitary-adrenal gland axis.
AB  - We tested the hypothesis that interleukin (IL)-1beta-induced cortisol synthesis
      stimulates alveolar fluid clearance in preterm fetuses. IL-1beta was administered
      subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without
      simultaneous cortisol synthesis inhibition by metyrapone. Fetuses were obtained
      by abdominal hysterotomy at 61 and 68 days gestation and instilled with isosmolar
      5% albumin in the lungs, and alveolar fluid movement was measured over 1 h from
      the change in alveolar protein concentration. Alveolar fluid clearance was
      induced at 61 days gestation and stimulated at 68 days gestation by IL-1beta,
      which both were attenuated by cortisol synthesis inhibition. Plasma ACTH and
      cortisol concentrations were increased by IL-1beta at both gestational ages, and
      metyrapone reduced cortisol concentrations. IL-1beta was mostly low or
      undetectable in both fetal and maternal blood. Prenatal alveolar fluid clearance,
      when present as well as IL-1beta induced, was always propranolol and amiloride
      sensitive, suggesting that beta-adrenoceptor stimulation and amiloride-sensitive
      Na+ channels were critical for fluid absorption. IL-1beta increased lung beta
      adrenoceptor density at gestation day 61, and cortisol synthesis inhibition
      attenuated the increased beta-adrenoceptor density. Epithelial Na+ channel and
      Na+-K+-ATPase subunit expressions were both increased by IL-1beta and attenuated
      by cortisol synthesis inhibition. These results may explain why babies delivered
      preterm after intrauterine inflammation have a reduced risk of developing severe
      respiratory distress.

PMID- 14644758
TI  - Inhibition of LPS- and CpG DNA-induced TNF-alpha response by oxidized
      phospholipids.
AB  - Lipid oxidation is commonly seen in the innate immune response, in which reactive
      oxygen intermediates are generated to kill pathogenic microorganisms. Although
      oxidation products of phospholipids have generally been regarded to play a role
      in a number of chronic inflammatory processes, several studies have shown that
      oxidized phospholipids inhibit the LPS-induced acute proinflammatory response in
      cultured macrophages and endothelial cells. We report in this study that oxidized
      1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), but not
      nonoxidized PAPC, significantly inhibits the LPS-induced TNF-alpha response in
      intact mice. Oxidized PAPC also inhibits the 2'-deoxyribo(cytidine-phosphate
      guanosine) (CpG) DNA-induced TNF-alpha response in cultured macrophages and
      intact mice. To elucidate the mechanisms of action, we show that oxidized PAPC,
      but not nonoxidized PAPC, inhibits the LPS- and CpG-induced activation of p38
      MAPK and the NF-kappaB cascade. These results suggest a role for oxidized lipids
      as a negative regulator in controlling the magnitude of the innate immune
      response. Further studies on the mechanisms of action may lead to development of
      a new type of anti-inflammatory drug for treatment of acute inflammatory diseases
      such as sepsis.

PMID- 14644759
TI  - Lysosomal acid lipase deficiency causes respiratory inflammation and destruction
      in the lung.
AB  - The functional roles of neutral lipids are poorly understood in the lung.
      Blocking cholesteryl ester and triglyceride metabolism in lysosomal acid lipase
      gene knockout mice (lal-/-) resulted in a high level of neutrophil influx in the
      lungs as early as 2 mo of age. Bronchoalveolar macrophages appeared foamy and
      gradually increased in number with age progression. Affymetrix GeneChip array
      analysis of lung mRNA showed increased levels of proinflammatory cytokine
      (including IL-1beta, IL-6, and TNF-alpha) and matrix metalloproteinase (including
      MMP-8, MMP-9, and MMP-12) expression in lal-/- mice. With age progression, some
      areas of lal-/- mice developed severe abnormal cell proliferation and alveolar
      remodeling. In other areas, alveolar destruction (i.e., emphysema) was observed.
      In addition, Clara cell hypertrophy and hyperplasia developed in conducting
      airways. The pathophysiological phenotypes in the lal-/- mouse lungs became more
      severe with increasing age. The studies support the concept that neutral lipid
      metabolites play essential roles in pulmonary homeostasis, inflammatory
      responses, remodeling, and injury repair.

PMID- 14644760
TI  - Developmental changes of intracellular Ca2+ transients in beating rat hearts.
AB  - Postnatal maturation of the rat heart is characterized by major changes in the
      mechanism of excitation-contraction (E-C) coupling. In the neonate, the t tubules
      and sarcoplasmic reticulum (SR) are not fully developed yet. Consequently, Ca(2+)
      induced Ca(2+) release (CICR) does not play a central role in E-C coupling. In
      the neonate, most of the Ca(2+) that triggers contraction comes through the
      sarcolemma. In this work, we defined the contribution of the sarcolemmal Ca(2+)
      entry and the Ca(2+) released from the SR to the Ca(2+) transient during the
      first 3 wk of postnatal development. To this end, intracellular Ca(2+) transients
      were measured in whole hearts from neonate rats by using the pulsed local field
      fluorescence technique. To estimate the contribution of each Ca(2+) flux to the
      global intracellular Ca(2+) transient, different pharmacological agents were
      used. Ryanodine was applied to evaluate ryanodine receptor-mediated Ca(2+)
      release from the SR, nifedipine for dihydropyridine-sensitive L-type Ca(2+)
      current, Ni(2+) for the current resulting from the reverse-mode Na(+)/Ca(2+)
      exchange, and mibefradil for the T-type Ca(2+) current. Our results showed that
      the relative contribution of each Ca(2+) flux changes considerably during the
      first 3 wk of postnatal development. Early after birth (1-5 days), the
      sarcolemmal Ca(2+) flux predominates, whereas at 3 wk of age, CICR from the SR is
      the most important. This transition may reflect the progressive development of
      the t tube-SR units characteristic of mature myocytes. We have hence directly
      defined in the whole beating heart the developmental changes of E-C coupling
      previously evaluated in single (acutely isolated or cultured) cells and
      multicellular preparations.

PMID- 14644761
TI  - Mechanisms of ADRF release from rat aortic adventitial adipose tissue.
AB  - Blood vessels are surrounded by variable amounts of adipose tissue. We showed
      earlier that adventitial adipose tissue inhibits rat aortic contraction by
      release of a transferable factor, adventitium-derived relaxing factor (ADRF),
      which activates smooth muscle K(+) channels. However, little is known about the
      mechanisms of ADRF release. Using isolated rat aortic rings and isometric
      contraction measurements, we show that ADRF release depends on extracellular
      [Ca(2+)] (EC(50) approximately 4.7 mM). ADRF effects do not involve neuronal
      presynaptic N-type Ca(2+) and Na(+) channels or vanilloid, cannabinoid, and CGRP
      receptors. ADRF release is strongly inhibited by the protein tyrosine kinase
      inhibitors genistein and tyrphostin A25. In contrast, daidzein, an inactive
      genistein analog, and the protein tyrosine kinase inhibitor ST638 had no effect.
      Protein kinase A inhibition by H89 also inhibited ADRF release, whereas the
      protein kinase G inhibitor KT-5823 had no effect. We propose that ADRF release is
      Ca(2+) dependent and is regulated by intracellular signaling pathways involving
      tyrosine kinase and protein kinase A. Furthermore, ADRF release does not depend
      on perivascular nerve endings.

PMID- 14644762
TI  - ACE inhibitors and statins acutely improve endothelial dysfunction of human
      coronary arterioles.
AB  - Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors as well
      as angiotensin II type 1 (AT(1)) receptor antagonists and statins reduces
      cardiovascular mortality in patients with coronary artery disease as well as
      chronic heart failure. Little is known about the acute effects of these compounds
      on vascular reactivity of coronary resistance vessels. Coronary arterioles were
      obtained from patients undergoing coronary bypass operation (atherosclerosis
      group) or valve replacement (control group). Responses to endothelium-dependent
      agonists (histamine, serotonin, and acetylcholine) as well as to the endothelium
      independent agonist sodium nitroprusside (SNP) were investigated under baseline
      conditions and after incubation (15 min) with lisinopril (ACE inhibitor),
      candesartan (AT(1) receptor antagonist), or fluvastatin. In atherosclerotic
      vessels, vasorelaxation was significantly reduced to all endothelium-dependent
      agonists but not, however, to SNP (77 +/- 8, -24 +/- 16, -46 +/- 24, and 98 +/-
      8% relaxation for histamine, serotonin, acetylcholine, and SNP, respectively).
      Lisinopril and fluvastatin but not candesartan significantly improved the
      responses to the endothelium-dependent agonists (lisinopril: 94 +/- 4, 17 +/- 22,
      and -20 +/- 13%; fluvastatin: 96 +/- 8, 23 +/- 21, and -25 +/- 18% relaxation for
      histamine, serotonin, and acetylcholine, respectively). The effect of lisinopril
      was prevented by pretreatment with a bradykinin antagonist (HOE-130) and
      dichloroisocoumarine, an inhibitor of kinine-forming enzymes. Pretreatment with a
      nitric oxide (NO) synthase inhibitor abolished the improvement of endothelial
      function by lisinopril and fluvastatin. Vascular reactivity in the control group
      was not influenced by any of the pharmacological interventions. The data
      demonstrate that in atherosclerosis, endothelium-dependent relaxation of coronary
      resistance arteries is severely compromised. The impairment can acutely be
      reversed by ACE inhibitors and statins via increasing the availability of NO.

PMID- 14644763
TI  - Hypothermia augments reactive oxygen species detected in the guinea pig isolated
      perfused heart.
AB  - Hypothermic perfusion of the heart decreases oxidative phosphorylation and
      increases NADH. Because O(2) and substrates remain available and respiration
      (electron transport system, ETS) may become impaired, we examined whether
      reactive oxygen species (ROS) exist in excess during hypothermic perfusion. A
      fiberoptic probe was placed on the left ventricular free wall of isolated guinea
      pig hearts to record intracellular ROS, principally superoxide (O(2)(-).), and an
      extracellular reactive nitrogen reactant, principally peroxynitrite (ONOO(-)), a
      product of nitric oxide (NO.) + O(2)(-). Hearts were loaded with dihydroethidium
      (DHE), which is oxidized by O(2)(-). to ethidium, or were perfused with l
      tyrosine, which is oxidized by ONOO(-) to dityrosine (diTyr). Shifts in
      fluorescence were measured online; diTyr fluorescence was also measured in the
      coronary effluent. To validate our methods and to examine the source and identity
      of ROS during cold perfusion, we examined the effects of a superoxide dismutase
      mimetic Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), the nitric
      oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and several
      agents that impair electron flux through the ETS: menadione, sodium azide
      (NaN(3)), and 2,3-butanedione monoxime (BDM). Drugs were given before or during
      cold perfusion. ROS measured by DHE was inversely proportional to the temperature
      between 37 degrees C and 3 degrees C. We found that perfusion at 17 degrees C
      increased DHE threefold versus perfusion at 37 degrees C; this was reversed by
      MnTBAP, but not by l-NAME or BDM, and was markedly augmented by menadione and
      NaN(3). Perfusion at 17 degrees C also increased myocardial and effluent diTyr
      (ONOO(-)) by twofold. l-NAME, MnTBAP, or BDM perfused at 37 degrees C before
      cooling or during 17 degrees C perfusion abrogated, whereas menadione and NaN(3)
      again enhanced the cold-induced increase in ROS. Our results suggest that
      hypothermia moderately enhances O(2)(-). generation by mitochondria, whereas
      O(2)(-). dismutation is markedly slowed. Also, the increase in O(2)(-). during
      hypothermia reacts with available NO. to produce ONOO(-), and drug-induced O(2)(
      ). dismutation eliminates the hypothermia-induced increase in O(2)(-).

PMID- 14644764
TI  - Low-flow vascular remodeling in the metabolic syndrome X.
AB  - Peripheral microvascular dysfunction is a common affliction in patients with the
      metabolic syndrome X. Previous studies have described a number of vascular
      impairments in vasomotor control in both human patients and animal models of
      syndrome X, but the net effect of these impairments on microvascular structure
      has not been examined. The goal of the current study was to test the hypothesis
      that syndrome X reduces muscle perfusion and induces vascular remodeling. The
      obese Zucker rat was used as a model of syndrome X, and the microcirculation of
      the hindlimb and brain were examined. Obese Zucker rats were obese,
      hyperlipidemic, hyperinsulinemic, and hyperglycemic. Blood flow to the hindlimb
      was reduced by 59% in obese rats relative to lean rats. Skeletal muscle
      resistance arteries of the hindlimb microcirculation of obese rats had thinner
      walls, smaller lumens, and reduced distensibility. Hindlimb microvessels from
      obese rats also demonstrated reduced expression of vascular smooth muscle cell
      markers. Each of these traits is consistent with low-flow remodeling. In
      contrast, the cerebral microcirculation, where flow is vigorously autoregulated,
      showed no vascular remodeling nor were there changes in microvascular smooth
      muscle marker expression. Neither physical activity nor muscle mass were
      significantly different between lean and obese rats. Taken together, these
      findings suggest that syndrome X, by reducing hindlimb blood flow, induces a
      marked remodeling of microcirculation to favor smaller, less distensible vessels.
      This remodeling may result in an architectural limitation of maximum perfusion
      capacity and may be an important maladaption in the progression of peripheral
      microvascular disease.

PMID- 14644765
TI  - Vasodilator effect and mechanism of action of vascular endothelial growth factor
      in skin vasculature.
AB  - Various laboratories have reported that local subcutaneous or subdermal injection
      of VEGF(165) at the time of surgery effectively attenuated ischemic necrosis in
      rat skin flaps, but the mechanism was not studied and enhanced angiogenesis was
      implicated. In the present study, we used the clinically relevant isolated
      perfused 6 x 16-cm pig buttock skin flap model to 1) test our hypothesis that
      VEGF(165) is a potent vasodilator and acute VEGF(165) treatment increases skin
      perfusion; and 2) investigate the mechanism of VEGF(165)-induced skin
      vasorelaxation. We observed that VEGF(165) (5 x 10(-16)-5 x 10(-11) M) elicited a
      concentration-dependent decrease in perfusion pressure (i.e., vasorelaxation) in
      skin flaps preconstricted with a submaximal concentration of norepinephrine (NE),
      endothelin-1, or U-46619. The VEGF(165)-induced skin vasorelaxation was confirmed
      using a dermofluorometry technique for assessment of skin perfusion. The
      vasorelaxation potency of VEGF(165) in NE-preconstricted skin flaps (pD(2) =
      13.57 +/- 0.31) was higher (P < 0.05) than that of acetylcholine (pD(2) = 7.08 +/
      0.24). Human placental factor, a specific VEGF receptor-1 agonist, did not
      elicit any vasorelaxation effect. However, a specific antibody to VEGF receptor-2
      (1 microg/ml) or a specific VEGF receptor-2 inhibitor (5 x 10(-6) M SU-1498)
      blocked the vasorelaxation effect of VEGF(165) in NE-preconstricted skin flaps.
      These observations indicate that the potent vasorelaxation effect of VEGF(165) in
      the skin vasculature is initiated by the activation of VEGF receptor-2.
      Furthermore, using pharmacological probes, we observed that the postreceptor
      signaling pathways of VEGF(165)-induced skin vasorelaxation involved activation
      of phospholipase C and protein kinase C, an increase in inositol 1,4,5
      trisphosphate activity, release of the intra-cellular Ca(2+) store, and
      synthesis/release of endothelial nitric oxide, which predominantly triggered the
      effector mechanism of VEGF(165)-induced vasorelaxation. This information
      provides, for the first time, an important insight into the mechanism of
      VEGF(165) protein or gene therapy in the prevention/treatment of ischemia in skin
      flap surgery and skin ischemic diseases.

PMID- 14644766
TI  - Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated
      by congenital NOS3 deficiency.
AB  - To investigate the role of endothelial nitric oxide synthase (NOS3) in left
      ventricular (LV) remodeling induced by chronic pressure overload, the impact of
      transverse aortic constriction (TAC) on LV structure and function was compared in
      wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice. Before TAC, LV wall
      thickness, mass, and fractional shortening were similar in the two mouse strains.
      Twenty-eight days after TAC, both WT and NOS3(-/-) mice had increased LV wall
      thickness and mass as well as decreased fractional shortening. Although the
      pressure gradient across the TAC was similar in both strains of mice 28 days
      after TAC, LV mass and posterior wall thickness were greater in NOS3(-/-) than in
      WT mice, whereas fractional shortening and the maximum rate of developed LV
      pressure were less. Diastolic function, as measured by the time constant of
      isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to
      a greater extent in NOS3(-/-) than in WT mice. The degree of myocyte hypertrophy
      and LV fibrosis was greater in NOS3(-/-) than in WT mice at 28 days after TAC.
      Mortality was greater in NOS3(-/-) than in WT mice 28 days after TAC. Long-term
      administration of hydralazine normalized the blood pressure and prevented the LV
      dilation in NOS3(-/-) mice but did not prevent the LV hypertrophy, dysfunction,
      and fibrosis associated with NOS3 deficiency after TAC. These results suggest
      that the absence of NOS3 augments LV dysfunction and remodeling in a murine model
      of chronic pressure overload.

PMID- 14644767
TI  - Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen
      phosphorylase inhibition in the conscious dog.
AB  - The aim of these studies was to investigate the effect of hyperglycemia with or
      without hyperinsulinemia on hepatic gluconeogenic flux, with the hypothesis that
      inhibition would be greatest with combined hyperglycemia/hyperinsulinemia. A
      glycogen phosphorylase inhibitor (BAY R3401) was used to inhibit glycogen
      breakdown in the conscious overnight-fasted dog, and the effects of a twofold
      rise in plasma glucose level (HI group) accompanied by 1) euinsulinemia (HG
      group) or 2) a fourfold rise in plasma insulin were assessed over a 5-h
      experimental period. Hormone levels were controlled using somatostatin with
      portal insulin and glucagon infusion. In the HG group, net hepatic glucose uptake
      and net hepatic lactate output substantially increased. There was little or no
      effect on the net hepatic uptake of gluconeogenic precursors other than lactate
      (amino acids and glycerol) or on the net hepatic uptake of free fatty acids
      compared with the control group. Consequently, whereas hyperglycemia had little
      effect on gluconeogenic flux to glucose 6-phosphate (G-6-P), net hepatic
      gluconeogenic flux was reduced because of increased hepatic glycolytic flux
      during hyperglycemia. Net hepatic glycogen synthesis was increased by
      hyperglycemia. The effect of hyperglycemia on gluconeogenic flux to G-6-P and net
      hepatic gluconeogenic flux was similar. We conclude that, in the absence of
      appreciable glycogen breakdown, the increase in glycolytic flux that accompanies
      hyperglycemia results in decreased net carbon flux to G-6-P but no effect on
      gluconeogenic flux to G-6-P.

PMID- 14644768
TI  - The ubiquitin-proteasome system is responsible for cysteine-responsive regulation
      of cysteine dioxygenase concentration in liver.
AB  - Hepatic cysteine dioxygenase (CDO) activity is a critical regulator of cellular
      cysteine concentration and availability of cysteine for anabolic processes and is
      markedly higher in animals fed diets containing excess sulfur amino acids
      compared with those fed levels at or below the requirement. Rat hepatocytes
      responded to a deficiency or excess of cysteine in the culture medium with a
      decrease or increase in CDO level but no change in CDO mRNA level. The cysteine
      analog, cysteamine, but not cysteine metabolites or thiol reagents, was also
      effective in increasing CDO. Inhibitors of the 26S proteasome blocked CDO
      degradation in cysteine-deficient cells but had little or no effect on CDO
      concentration in hepatocytes cultured with excess cysteine. High-molecular-mass
      CDO-ubiquitin conjugates were observed in cells cultured in cysteine-deficient
      medium, whether or not proteasome inhibitor was present, but these CDO-ubiquitin
      conjugates were not observed in cells cultured in cysteine-supplemented medium
      with or without proteasome inhibitor. Similar results were observed for
      degradation of recombinant CDO expressed in human heptocarcinoma cells cultured
      in cysteine-deficient or cysteine-supplemented medium. CDO is an example of a
      mammalian enzyme that is robustly regulated via its substrate, with the presence
      of substrate blocking the ubiquitination of CDO and, hence, the targeting of CDO
      for proteasomal degradation. This regulation occurs in primary hepatocytes in a
      manner that corresponds with changes observed in intact animals.

PMID- 14644769
TI  - Regulation of MDCK cell-substratum adhesion by RhoA and myosin light chain kinase
      after ATP depletion.
AB  - The attachment of epithelial cells to the extracellular matrix substratum is
      essential for their differentiation and polarization. Despite this, the precise
      adhesion mechanism and its regulation are poorly understood. In the kidney, an
      ischemic insult causes renal tubular epithelial cells to detach from the basement
      membrane, even though they remain viable. To understand this phenomenon, and to
      probe the regulation of epithelial cell attachment, we used a model system
      consisting of newly adherent Madin-Darby canine kidney (MDCK) cells subjected to
      ATP depletion to mimic ischemic injury. We found that MDCK cells detach from
      collagen I after 60 min of ATP depletion but reattach when resupplied with
      glucose. Detachment is not caused by degradation or endocytosis of beta(1)
      integrins, which mediate attachment to collagen I. Basal actin filaments and
      paxillin-containing adhesion complexes are disrupted by ATP depletion and quickly
      reform on glucose repletion. However, partial preservation of basal actin by
      overexpression of constitutively active RhoA does not significantly affect cell
      detachment. Furthermore, Y-27632, an inhibitor of the RhoA effector Rho-kinase,
      does not prevent reattachment of cells on glucose addition, even though
      reformation of central stress fibers and large adhesion complexes is blocked. In
      contrast, reattachment of ATP-depleted cells and detachment of cells not
      previously subjected to ATP depletion are prevented by ML-7, an inhibitor of
      myosin light chain kinase (MLCK). We conclude that initial adherence of MDCK
      cells to a collagen I substratum is mediated by peripheral actin filaments and
      adhesion complexes regulated by MLCK but not by stress fibers and adhesion
      complexes controlled by RhoA.

PMID- 14644770
TI  - Plasma membrane aquaporin activity can affect the rate of apoptosis but is
      inhibited after apoptotic volume decrease.
AB  - Apoptosis is characterized by a conserved series of morphological events
      beginning with the apoptotic volume decrease (AVD). This study investigated a
      role for aquaporins (AQPs) during the AVD. Inhibition of AQPs blocked the AVD in
      ovarian granulosa cells undergoing growth factor withdrawal and blocked
      downstream apoptotic events such as cell shrinkage, changes in the mitochondrial
      membrane potential, DNA degradation, and caspase-3 activation. The effects of AQP
      inhibition on the AVD and DNA degradation were consistent in thymocytes and with
      two additional apoptotic signals, thapsigargin and C(6)-ceramide. Overexpression
      of AQP-1 in Chinese hamster ovary (CHO-AQP-1) cells enhanced their rate of
      apoptosis. The AVD is driven by loss of K(+) from the cell, and we hypothesize
      that after the AVD, AQPs become inactive, which halts further water loss and
      allows K(+) concentrations to decrease to levels necessary for apoptotic enzyme
      activation. Swelling assays on granulosa cells, thymocytes, and CHO-AQP-1 cells
      revealed that indeed, the shrunken (apoptotic) subpopulation has very low water
      permeability compared with the normal-sized (nonapoptotic) subpopulation. In
      thymocytes, AQP-1 is present and was shown to colocalize with the plasma membrane
      receptor tumor necrosis factor receptor-1 (TNF-R1) both before and after the AVD,
      which suggests that this protein is not proteolytically cleaved and remains on
      the cell membrane. Overall, these data indicate that AQP-mediated water loss is
      important for the AVD and downstream apoptotic events, that the water
      permeability of the plasma membrane can control the rate of apoptosis, and that
      inactivation after the AVD may help create the low K(+) concentration that is
      essential in apoptotic cells. Furthermore, inactivation of AQPs after the AVD
      does not appear to be through degradation or removal from the cell membrane.

PMID- 14644771
TI  - Increased vascular endothelial growth factor may account for elevated level of
      plasminogen activator inhibitor-1 via activating ERK1/2 in keloid fibroblasts.
AB  - Keloids are characterized as an "overexuberant" healing response in which
      disequilibrium between production and catabolism of extracellular matrix (ECM)
      occurs. Previous studies from our laboratory and others demonstrate an
      intrinsically higher level of plasminogen activator inhibitor-1 (PAI-1)
      expression in keloid tissues and cultured fibroblasts compared with normal
      bordering skin. These findings support the concept that an altered balance of
      activator and inhibitor activities in the plasminogen system, in particular, an
      overexpression of PAI-1, may partly contribute to keloid formation and tissue
      fibrosis. Vascular endothelial growth factor (VEGF) has been implicated as a
      critical factor in regulating angiogenesis and inflammation under both
      physiological and pathological conditions. This study was designed to assess
      whether VEGF plays a role in keloid fibrosis. We report that VEGF was expressed
      at higher levels in keloid tissues and their derived fibroblasts compared with
      their associated normal skin. We have further demonstrated that VEGF stimulated
      the expression of PAI-1, but not urokinase plasminogen activator (uPA), in keloid
      fibroblasts at both mRNA and protein levels, in a dose- and time-dependent
      manner. However, treatment of normal skin fibroblasts with VEGF exerted little
      effects on PAI-1 gene expression. Additionally, we have characterized for the
      first time that the extracellular signal-regulated kinase (ERK)1/2 signaling
      pathway is mainly involved in VEGF-induced PAI-1 expression and have demonstrated
      its potential as a target molecule for modulation of scar fibrosis. These
      findings suggest that VEGF may play an important role in keloid formation by
      altering ECM homeostasis toward a state of impaired degradation and excessive
      accumulation.

PMID- 14644772
TI  - Depletion of plasma membrane cholesterol dampens hydrostatic pressure and shear
      stress-induced mechanotransduction pathways in osteoblast cultures.
AB  - The preferential association of cholesterol and sphingolipids within plasma
      membranes forms organized compartments termed lipid rafts. Addition of caveolin
      proteins to this lipid milieu induces the formation of specialized invaginated
      plasma membrane structures called caveolae. Both lipid rafts and caveolae are
      purported to function in vesicular transport and cell signaling. We and others
      have shown that disassembly of rafts and caveolae through depletion of plasma
      membrane cholesterol mitigates mechanotransduction processes in endothelial
      cells. Because osteoblasts are subjected to fluid-mechanical forces, we
      hypothesize that cholesterol-rich plasma membrane microdomains also serve the
      mechanotransduction process in this cell type. Cultured human fetal osteoblasts
      were subjected to either sustained hydrostatic pressure or laminar shear stress
      using a pressure column or parallel-plate apparatus, respectively. We found that
      sustained hydrostatic pressure induced protein tyrosine phosphorylation,
      activation of extracellular signal-regulated kinase (ERK)1/2, and enhanced
      expression of c-fos in both time- and magnitude-dependent manners. Similar
      responses were observed in cells subjected to laminar shear stress. Both
      sustained hydrostatic pressure- and shear stress-induced signaling were
      significantly reduced in osteoblasts pre-exposed to either filipin or methyl-beta
      cyclodextrin. These mechanotransduction responses were restored on reconstitution
      of lipid rafts and caveolae, which suggests that cholesterol-rich plasma membrane
      microdomains participate in the mechanotransduction process in osteoblasts. In
      addition, mechanical force-induced phosphoproteins were localized within caveolin
      containing membranes. These data support the concept that lipid rafts and
      caveolae serve a general function as cell surface mechanotransduction sites
      within the plasma membrane.

PMID- 14644773
TI  - Modulation of epithelial tubule formation by Rho kinase.
AB  - We have developed a model system for studying integrin regulation of mammalian
      epithelial tubule formation. Application of collagen gel overlays to Madin-Darby
      canine kidney (MDCK) cells induced coordinated disassembly of junctional
      complexes that was accompanied by lamellipodia formation and cell rearrangement
      (termed epithelial remodeling). In this study, we present evidence that the Rho
      signal transduction pathway regulates epithelial remodeling and tubule formation.
      Incubation of MDCK cells with collagen gel overlays facilitated formation of
      migrating lamellipodia with membrane-associated actin. Inhibitors of myosin II
      and actin prevented lamellipodia formation, which suggests that actomyosin
      function was involved in regulation of epithelial remodeling. To determine this,
      changes in myosin II distribution, function, and phosphorylation were studied
      during epithelial tubule biogenesis. Myosin II colocalized with actin at the
      leading edge of lamellipodia thereby providing evidence that myosin is important
      in epithelial remodeling. This possibility is supported by observations that
      inhibition of Rho kinase, a regulator of myosin II function, alters formation of
      lamellipodia and results in attenuated epithelial tubule development. These data
      and those demonstrating myosin regulatory light-chain phosphorylation at the
      leading edge of lamellipodia strongly suggest that Rho kinase and myosin II are
      important modulators of epithelial remodeling. They support a hypothesis that the
      Rho signal transduction pathway plays a significant role in regulation of
      epithelial tubule formation.

PMID- 14644774
TI  - Caffeine sensitivity of native RyR channels from normal and malignant
      hyperthermic pigs: effects of a DHPR II-III loop peptide.
AB  - Enhanced sensitivity to caffeine is part of the standard tests for susceptibility
      to malignant hyperthermia (MH) in humans and pigs. The caffeine sensitivity of
      skeletal muscle contraction and Ca(2+) release from the sarcoplasmic reticulum is
      enhanced, but surprisingly, the caffeine sensitivity of purified porcine
      ryanodine receptor Ca(2+)-release channels (RyRs) is not affected by the MH
      mutation (Arg(615)Cys). In contrast, we show here that native malignant
      hyperthermic pig RyRs (incorporated into lipid bilayers with RyR-associated
      lipids and proteins) were activated by caffeine at 100- to 1000-fold lower
      concentrations than native normal pig RyRs. In addition, the results show that
      the mutant ryanodine receptor channels were less sensitive to high-affinity
      activation by a peptide (C(S)) that corresponds to a part of the II-III loop of
      the skeletal dihydropyridine receptor (DHPR). Furthermore, subactivating
      concentrations of peptide C(S) enhanced the response of normal pig and rabbit
      RyRs to caffeine. In contrast, the caffeine sensitivity of MH RyRs was not
      enhanced by the peptide. These novel results showed that in MH-susceptible pig
      muscles 1). the caffeine sensitivity of native RyRs was enhanced, 2). the
      sensitivity of RyRs to a skeletal II-III loop peptide was depressed, and 3). an
      interaction between the caffeine and peptide C(S) activation mechanisms seen in
      normal RyRs was lost.

PMID- 14644775
TI  - Description of glucose transport in isolated bovine mammary epithelial cells by a
      three-compartment model.
AB  - Initial rates of glucose entry into isolated bovine mammary epithelial cells
      display moderate degrees of asymmetry and cooperative interactions between export
      and import sites. The present study examined the hypothesis that these kinetic
      features are due to compartmentalization of intracellular glucose. Net uptake of
      3-O-methyl-d-[1-(3)H]glucose (3-OMG) by isolated bovine mammary epithelial cells
      was measured at 37 degrees C. The time course of 3-OMG net uptake was better
      fitted by a double-exponential equation than by a single- or triple-exponential
      equation. Compartmental analysis of the time course curve suggested that
      translocated 3-OMG is distributed into two compartments with fractional volumes
      of 32.6 +/- 5.7% and 67.4 +/- 5.7%, respectively. The results support the view
      that glucose transport in bovine mammary epithelial cells is a multistep process
      consisting of two serial steps: fast, carrier-mediated, symmetric translocation
      of sugar across the cell plasma membrane into a small compartment and subsequent
      slow exchange of posttranslocated sugar between two intracellular compartments. A
      three-compartment model of this system successfully simulated the observed time
      course of 3-OMG net uptake and the observed dependence of unidirectional entry
      rates on intra- and extracellular 3-OMG concentrations. Simulations indicated
      that backflux of radiolabeled sugar from the small compartment to extracellular
      space during 15 s of incubation gives rise to the apparent asymmetry, trans
      stimulation, and cooperativity of mammary glucose transport kinetics. The fixed
      site carrier model overestimated the rate of glucose accumulation in cells, and
      its features can be accounted for by the compartmentalization of intracellular
      sugar.

PMID- 14644776
TI  - Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress.
AB  - The ability to control osmotic balance is essential for cellular life. Cellular
      osmotic homeostasis is maintained by accumulation and loss of inorganic ions and
      organic osmolytes. Although osmoregulation has been studied extensively in many
      cell types, major gaps exist in our molecular understanding of this essential
      process. Because of its numerous experimental advantages, the nematode
      Caenorhabditis elegans provides a powerful model system to characterize the
      genetic basis of animal cell osmoregulation. We therefore characterized the
      ability of worms to adapt to extreme osmotic stress. Exposure of worms to high
      salt growth agar causes rapid shrinkage. Survival is normal on agar containing up
      to 200 mM NaCl. When grown on 200 mM NaCl for 2 wk, worms are able to survive
      well on agar containing up to 500 mM NaCl. HPLC analysis demonstrated that levels
      of the organic osmolyte glycerol increase 15- to 20-fold in nematodes grown on
      200 mM NaCl agar. Accumulation of glycerol begins 3 h after exposure to
      hypertonic stress and peaks by 24 h. Glycerol accumulation is mediated primarily
      by synthesis from metabolic precursors. Consistent with this finding,
      hypertonicity increases transcriptional expression of glycerol 3-phosphate
      dehydrogenase, an enzyme that is rate limiting for hypertonicity-induced glycerol
      synthesis in yeast. Worms adapted to high salt swell and then return to their
      initial body volume when exposed to low-salt agar. During recovery from
      hypertonic stress, glycerol levels fall rapidly and glycerol excretion increases
      approximately fivefold. Our studies provide the first description of osmotic
      adaptation in C. elegans and provide the foundation for genetic and functional
      genomic analysis of animal cell osmoregulation.

PMID- 14644777
TI  - Angiotensin II-induced MMP-2 release from endothelial cells is mediated by TNF
      alpha.
AB  - Angiotensin II (ANG II) has been etiologically linked to vascular disease;
      however, its role in the alterations of endothelial function that occur in
      vascular disorders is not completely understood. Matrix metalloproteinases (MMPs)
      and proinflammatory cytokines are involved in the pathological remodeling of
      blood vessels that occurs in vascular disease. In this study we evaluated the
      effects of ANG II on tumor necrosis factor (TNF)-alpha and MMP-2 production in
      endothelial cells. Human umbilical vein endothelial cells (HUVECs) were
      stimulated with ANG II (0.1-10 microM) for 24 h, in the presence or absence of
      antagonists of ANG II type 1 (AT(1)R) and type 2 (AT(2)R) receptors, and the
      production and release of TNF-alpha and MMP-2 were assessed. ANG II increased TNF
      alpha mRNA and protein expression and the release of bioactive TNF-alpha.
      Moreover, ANG II induced MMP-2 release and reduced the secretion of tissue
      inhibitor of MMP (TIMP)-2 from endothelial cells. To elucidate whether endogenous
      TNF-alpha could mediate the effects of ANG II on MMP-2 release, cells were
      pretreated with anti-TNF-alpha neutralizing antibodies or pentoxifylline (an
      inhibitor of TNF-alpha synthesis). TNF-alpha inhibition prevented the secretion
      of MMP-2 induced by ANG II. Furthermore, AT(1)R antagonism with candesartan
      prevented the formation of MMP-2 and TNF-alpha and the reduction of TIMP-2
      induced by ANG II. These results indicate that ANG II, via AT(1)R, modulates the
      secretion of TNF-alpha and MMP-2 from endothelial cells and that TNF-alpha
      mediates the effects of ANG II on MMP-2 release.

PMID- 14644778
TI  - Contribution of PKC-dependent and -independent processes in temporal ERK
      regulation by ET-1, PDGF, and EGF in rat myometrial cells.
AB  - Endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and epidermal growth
      factor (EGF) stimulated thymidine incorporation with different efficiency (PDGF
      >> EGF = ET-1) in rat myometrial cells. They also stimulated ERK activation,
      which culminated at 5 min and then declined to reach a plateau (at 45 min: EGF >
      90%, PDGF = 50%, and ET-1 < 10% of maximum). Inhibition and downregulation of PKC
      demonstrated that ERK activation at 5 min involved PKC delta and -zeta for ET-1
      and PKC alpha plus another PKC isoform for PDGF. By contrast, the EGF response
      did not involve PKC. Stimulation of Ras was more important with EGF than with
      PDGF, with ET-1 being the weakest activator. The simultaneous incubation of the
      cells with EGF and ET-1 potentiated the ERK activation at 5 min and mimicked the
      plateau phase obtained with PDGF. Under these conditions thymidine incorporation
      was comparable to that induced by PDGF. Taken together, our results indicated
      that the kinetic profile of ERK activation and its impact on cell proliferation
      can be modulated by the differential involvement of PKC isoforms and the
      amplitude of Ras activation.

PMID- 14644779
TI  - Diazepam inhibits organophosphate-induced central respiratory depression.
AB  - OBJECTIVES: Current evidence suggests that mortality from acute organophosphate
      (OP) poisoning is partially mediated through central nervous system (CNS)
      respiratory center depression (CRD). However, the exact mechanism of OP-induced
      CRD is unknown. In these studies, the authors investigated the hypothesis that OP
      induced CRD is the result of overstimulation of CNS respiratory centers. METHODS:
      Wistar rats received prophylaxis with either normal saline (controls), atropine,
      the peripherally acting anticholinergics glycopyrrolate (GLYC), ipratropium
      bromide (IB), or the CNS respiratory center attenuator diazepam. To determine if
      a dual CNS/peripheral cholinergic mechanism is responsible for animal death, two
      additional groups received combination treatment with diazepam plus either IB or
      GLYC. All treatments were completed 5 minutes before OP with subcutaneous
      dichlorvos. Differences in 10-minute and 24-hour mortality were assessed by the
      Fisher exact test. RESULTS: Dichlorvos poisoning resulted in profound
      fasciculations without obvious seizure in all cohorts. In controls and animals
      treated with peripherally acting anticholinergics, fasciculations were followed
      by sedation and respiratory arrest (0% 10-minute survival in all cohorts). In
      contrast, pretreatment with either atropine or diazepam significantly improved 10
      minute survival (100% and 44%, respectively). Although GLYC or IB afforded no
      protection when given alone, when delivered in conjunction with diazepam, the
      combination significantly improved survival (both groups 88% at 24 hours),
      suggesting a dual CNS/pulmonary muscarinic mechanism of lethality. CONCLUSIONS:
      The central respiratory depressant diazepam paradoxically attenuates
      organophosphate-induced respiratory depression, and when combined with
      peripherally acting anticholinergic agents, reduces mortality in a rat model of
      severe acute OP poisoning.

PMID- 14644780
TI  - Short-axis versus long-axis approaches for teaching ultrasound-guided vascular
      access on a new inanimate model.
AB  - OBJECTIVES: To determine whether a short-axis (SA) or long-axis (LA) ultrasound
      (US) approach to guidance for line placement results in faster vascular access
      for novice US users. Also, to assess if there was a difference in the number of
      skin penetrations and needle redirections between the two guidance techniques.
      METHODS: This was a prospective, randomized, observational study of emergency
      medicine (EM) residents at a Level I trauma center. A gelatin dessert and dietary
      fiber supplement mixture, providing a realistic US image, were placed inside a
      synthetic arm skin that is used for training phlebotomists and contains a rubber
      vein filled with red fluid at a depth of 1.5 cm. After a 30-minute tutorial on US
      guided vascular access, EM residents were randomized to one of two groups. Group
      one attempted SA first and then the LA. Group two tried LA first followed by the
      SA. Time from skin break to vein cannulation, number of skin breaks and needle
      redirections, and difficulty of access on a 10-point Likert scale as reported by
      residents were recorded. Statistical analysis included paired Student's t-test
      with 95% confidence intervals (95% CIs). RESULTS: Seventeen EM residents
      participated. The mean times to vein cannulation in SA and LA were 2.36 minutes
      (95% CI = 1.15 to 3.58) and 5.02 minutes (95% CI = 2.90 to 7.13), respectively (p
      = 0.03). The mean numbers of skin breaks for SA and LA were 4.18 (95% CI = 1.18
      to 7.17) and 5.76 (95% CI = 1.83 to 9.69), respectively (p = 0.49). The mean
      numbers of needle redirections in the SA and LA were 13.71 (95% CI = 4.51 to
      22.89) and 18.17 (95% CI = 7.95 to 28.40), respectively (p = 0.51). The mean
      difficulty scores for SA and LA were 3.99 (95% CI = 2.42 to 5.67) and 5.86 (95%
      CI = 4.32 to 7.40), respectively (p = 0.17). CONCLUSIONS: Novice US users obtain
      vascular access faster with an SA approach on an inanimate model.

PMID- 14644781
TI  - A risk score to predict arrhythmias in patients with unexplained syncope.
AB  - OBJECTIVES: To develop and validate a risk score predicting arrhythmias for
      patients with syncope remaining unexplained after emergency department (ED)
      noninvasive evaluation. METHODS: One cohort of 175 patients with unexplained
      syncope (Geneva, Switzerland) was used to develop and cross-validate the risk
      score; a second cohort of 269 similar patients (Pittsburgh, PA) was used to
      validate the system. Arrhythmias as a cause of syncope were diagnosed by cardiac
      monitoring or electrophysiologic testing. Data from the patient's history and 12
      lead emergency electrocardiography (ECG) were used to identify predictors of
      arrhythmias. Logistic regression was used to identify predictors for the risk
      score system. Risk-score performance was measured by comparing the proportions of
      patients with arrhythmias at various levels of the score and receiver operating
      characteristic (ROC) curves. RESULTS: The prevalence of arrhythmic syncope was
      17% in the derivation cohort and 18% in the validation cohort. Predictors of
      arrhythmias were abnormal ECG (odds ratio [OR]: 8.1, 95% confidence interval
      [CI]=3.0 to 22.7), a history of congestive heart failure (OR: 5.3, 95% CI=1.9 to
      15.0), and age older than 65 (OR: 5.4, 95% CI=1.1 to 26.0). In the derivation
      cohort, the risk of arrhythmias ranged from 0% (95% CI=0 to 6) in patients with
      no risk factors to 6% (95% CI=1 to 15) for patients with one risk factor, 41%
      (95% CI=26 to 57) for patients with two risk factors, and 60% (95% CI = 32 to 84)
      for those with three risk factors. In the validation cohort, these proportions
      varied from 2% (95% CI=0 to 7) with no risk factors to 17% (95% CI=10 to 27) with
      one risk factor, 35% (95% CI=24 to 46) with two risk factors, and 27% (95% CI=6
      to 61) with three risk factors. Areas under the ROC curves ranged from 0.88 (95%
      CI=0.84 to 0.91) for the derivation cohort to 0.84 (95% CI=0.77 to 0.91) after
      cross-validation within the same cohort and 0.75 (95% CI=0.68 to 0.81) for the
      external validation cohort. CONCLUSIONS: In patients with unexplained syncope, a
      risk score based on clinical and ECG factors available in the ED identifies
      patients at risk for arrhythmias.

PMID- 14644782
TI  - Resident perceptions of medical errors in the emergency department.
AB  - OBJECTIVES: To evaluate resident experience and perceptions of medical error
      associated with emergency department (ED) care. METHODS: Using a semistructured
      interview protocol, three researchers interviewed 26 randomly selected medical,
      surgical, and obstetrics residents regarding medical error. The authors chose a
      16-case subset of incidents involving ED care for initial review. Interview
      transcripts were reviewed iteratively to draw out recurrent categories and
      themes. Two investigators separately analyzed all cases to ensure common
      understanding and agreement. RESULTS: Most cases involved misdiagnosis, misread
      radiographs, or inappropriate disposition. Two thirds of the case patients died
      or experienced delays in care. Residents felt that the complexity of the
      patients, as well as the complexity of their own jobs, contributed to error.
      Attending supervision, nurse evaluation, and additional physician involvement all
      were noted to be important checks within the hospital system. Residents most
      often held the ED responsible for error. In addition, they deemed themselves,
      their teams, and their lack of training responsible. Though residents often
      discussed events with their admitting teams, follow-up with the ED or other
      associated individuals was uncommon. The findings revealed seven common themes
      that include factors contributing to errors, checks and adaptations, and follow
      up of the event. CONCLUSIONS: Residents are aware of medical error and able to
      recall events in detail. Whereas events are discussed among inpatient teams,
      little information finds its way back to the ED, potentially resulting in
      misunderstandings between departments and hindering learning from events. In
      depth interviewing allows a nuanced and detailed approach to error analysis.

PMID- 14644783
TI  - HandiStroke: a handheld tool for the emergent evaluation of acute stroke
      patients.
AB  - BACKGROUND: The management of acute stroke is time-sensitive. Clinical decision
      making requires data not only from laboratory testing and neuroimaging, but also
      from a detailed history and neurologic examination. The neurologic examination
      provides baseline information and assists in differentiating acute stroke from
      its mimickers. There is a need for tools to facilitate the evaluation and
      decision making in the acute stroke patient to make the correct diagnosis and,
      when indicated, to properly administer intravenous thrombolytic therapy.
      OBJECTIVES: The goals of this project were to create a standardized, handheld
      software program to aid physicians in their evaluation of patients presenting to
      the emergency department (ED) with acute ischemic stroke, and to create an
      educational tool with which residents and other health care professionals can
      gain a level of proficiency in treating these patients. RESULTS: A comprehensive
      handheld tool was created that incorporates a National Institutes of Health
      Stroke Scale (NIHSS) calculator, inclusion criteria, absolute contraindications,
      and relative warnings for thrombolytic use (i.e., recombinant tissue plasminogen
      activator), and a weight-based dosing calculator that flows in a logical and
      clinically relevant format. Additionally, the program includes reference
      materials and guidelines for clinical management to further assist the clinician.
      CONCLUSIONS: Applications of this program include reformatting for use as a data
      gathering tool in future clinical studies investigating the treatment of stroke
      patients, increasing the use and documentation of the NIHSS within the ED in
      acute ischemic stroke patients, and improving protocol adherence for rt-PA use.

PMID- 14644784
TI  - Patient opinions and attitudes toward medical student procedures in the emergency
      department.
AB  - OBJECTIVES: To determine emergency department (ED) patients' preferences about
      having medical students perform procedures as part of medical student clinical
      training. METHODS: A questionnaire was administered to a sequential sample of 150
      patients of 196 approached (76.5% participation rate) in a teaching hospital ED.
      Patients were asked how many procedures a medical student should have performed
      on other patients before the participant would allow the student to perform the
      procedure on them. The procedures included venipuncture, starting an IV, suturing
      the face, suturing the arm, performing a lumbar puncture, starting a central
      line, inserting a nasogastric tube, intubation, and cardioversion. RESULTS: If
      they had their preference, only a minority of patients would allow medical
      students to perform their first procedure on them for any of the procedures (a
      high of 42% for venipuncture, with a low of 7% for a lumbar puncture). Many
      patients prefer that medical students never perform a procedure on them (a high
      of 56% for a central line and a low of 21% for venipuncture). Patient beliefs
      were independent of age, gender, or insurance status. CONCLUSIONS: Patients are
      reluctant to be a medical student's first patient when it comes to procedures in
      the ED. This has implications for medical training and informed consent.

PMID- 14644785
TI  - Faculty development: what is faculty development?
AB  - Faculty development is an organized, goal-directed process to achieve career
      progression and growth. Inherent in this process is the acquisition of skills
      that enable one to contribute in a meaningful way to the advancement of a field
      of interest, whether educational, operational, or scientific. The process
      requires attention to technical skills, personal attributes, and explicit goals.
      Supportive mentorship is optimal. This document outlines important concepts and
      identifies helpful resources for academic faculty members. Additional resources
      are available at http://www.saem.org/facdev/index.htm.

PMID- 14644786
TI  - Diagnosis clusters for emergency medicine.
AB  - OBJECTIVES: Aggregated emergency department (ED) data are useful for research, ED
      operations, and public health surveillance. Diagnosis data are widely available
      as The International Classification of Diseases, version, 9, Clinical
      Modification (ICD-9-CM) codes; however, there are over 24,000 ICD-9-CM code
      descriptor pairs. Standardized groupings (clusters) of ICD-9-CM codes have been
      developed by other disciplines, including family medicine (FM), internal medicine
      (IM), inpatient care (Agency for Healthcare Research and Quality [AHRQ]), and
      vital statistics (NCHS). The purpose of this study was to evaluate the coverage
      of four existing ICD-9-CM cluster systems for emergency medicine. METHODS: In
      this descriptive study, four cluster systems were used to group ICD-9-CM final
      diagnosis data from a southeastern university tertiary referral center. Included
      were diagnoses for all ED visits in July 2000 and January 2001. In the
      comparative analysis, the authors determined the coverage in the four cluster
      systems, defined as the proportion of final diagnosis codes that were placed into
      clusters and the frequencies of diagnosis codes in each cluster. RESULTS: The
      final sample included 7,543 visits with 19,530 diagnoses. Coverage of the ICD-9
      CM codes in the ED sample was: AHRQ, 99%; NCHS, 88%; FM, 71%; IM, 68%. Seventy
      six percent of the AHRQ clusters were small, defined as grouping <1% of the
      diagnosis codes in the sample. CONCLUSIONS: The AHRQ system provided the best
      coverage of ED ICD-9-CM codes. However, most of the clusters were small and not
      significantly different from the raw data.

PMID- 14644787
TI  - Emergency department blood or body fluid exposure evaluations and HIV
      postexposure prophylaxis usage.
AB  - OBJECTIVES: To determine the frequency and type of patient visits for blood or
      body fluid exposures to a large, urban emergency department (ED); to ascertain
      the frequency that human immunodeficiency virus (HIV) post-exposure prophylaxis
      (PEP) was prescribed for these exposures; and to compare HIV PEP usage by patient
      group, occupation, and exposure type. METHODS: Retrospective medical record
      review of ED patient visits (January 1, 1995, through June 30, 2001) extracted
      from two separate billing record computerized databases using 14 ICD-9 codes that
      defined blood or body fluid exposures. RESULTS: Of the 1,436 visits, 22% were by
      health care workers (HCWs) and 78% by non-HCW adults, adolescents, or children.
      Sixty percent of the HCWs sustained needlestick or sharp injuries, 73% of non-HCW
      adults had human bites, and 81% of adolescents and children had sexual exposures.
      Nurses were the largest group of HCWs, whereas police, correction officers, and
      security guards were the largest group of non-HCWs exposed at work. HCWs and non
      HCW adults who sustained nonsexual exposures were much more likely to present for
      an evaluation within 24 hours than adolescents or children who suffered sexual
      assault (p<0.001). HIV PEP was prescribed 143 times: 92 to HCWs and 51 to all
      other patients. HIV PEP was most often prescribed to HCWs sustaining needlestick
      injuries. CONCLUSIONS: The majority of patients were not HCWs, which attests to
      the need for national, nonoccupational blood or body fluid management guidelines.
      There may be particular groups who would benefit from educational campaigns
      informing them of the need for early-intervention, postexposure measures to
      prevent an HIV infection.

PMID- 14644788
TI  - Rates of at-risk drinking among patients presenting to the emergency department
      with occupational and nonoccupational injury.
AB  - OBJECTIVES: To compare the characteristics and rates of at-risk drinking among
      patients presenting to the emergency department (ED) with occupational and
      nonoccupational injury. METHODS: Cross-sectional survey of injured patients
      presenting to a university hospital ED. Injured patients were prospectively
      identified, and consenting patients completed a survey including questions
      regarding quantity/frequency of alcohol use, TWEAK, CAGE, and work-relatedness of
      injury. Major trauma and motor-vehicle collisions were excluded. Demographic and
      injury information was obtained from the medical record. Patients with a TWEAK
      score > or =3, CAGE score > or =2, or who exceeded NIAAA quantity/frequency
      guidelines were defined as at-risk drinkers. Analysis utilized the Student t-test
      for continuous variables, and frequency and chi-square analysis for categorical
      variables. RESULTS: Among 3,476 enrolled patients, 766 (22%) had work injuries
      and 2,710 (78%) had nonwork injuries. Patients with work injuries were as likely
      as patients with nonwork injuries to be at-risk drinkers; 35% of patients with an
      occupational injury and 36% of those with a nonoccupational injury were at-risk
      drinkers (odds ratio = 0.96). CONCLUSIONS: Patients presenting to the ED with an
      occupational injury have rates of at-risk drinking similar to other injury
      patients, and may be an important group in which to target brief alcohol
      interventions.

PMID- 14644789
TI  - Determinants of emergency department visits by older adults: a systematic review.
AB  - OBJECTIVES: To conduct a systematic review of the literature on the determinants
      of hospital emergency department (ED) visits by elders, using a modification of
      the Andersen behavioral model of health services, adapted to explain ED
      utilization. METHODS: Relevant articles were identified through MEDLINE and a
      search of reference lists and personal files. Studies of populations aged 65 or
      older in which ED visits were a study outcome were included if they were:
      original, not restricted to a particular medical condition, written in English or
      French, and investigated one or more determinants. Data were abstracted and
      checked by two authors using a standard protocol. RESULTS: Fourteen studies
      (reported in 15 articles) were reviewed, 10 community-based and four using
      clinical samples. Among ten studies that measured multiple determinants,
      determinants reported from multivariate analyses included measures of need
      (perceived and evaluated health status, prior utilization), predisposing factors
      (health beliefs and sociodemographic variables), and enabling factors (physician
      availability, regular source of care, family resources, geographical access to
      services). CONCLUSIONS: Need is usually the primary determinant of ED visits in
      older people. Controlling for need, predisposing and enabling factors that
      promote access to primary medical care are associated with reduced ED
      utilization.

PMID- 14644790
TI  - Contracting with children and helmet distribution in the emergency department to
      improve bicycle helmet use.
AB  - OBJECTIVES: To determine whether injury prevention counseling and behavioral
      counseling delivered in the emergency department (ED) could result in increases
      in self-reported bicycle helmet use. METHODS: The authors undertook a trial of
      counseling in 222 children recruited in an urban ED between August 2000 and
      October 2001. All consenting patients in the ED aged 5 to 15 years who did not
      have life-threatening conditions were eligible. One hundred nine children were
      assigned to the control group on the basis of attendance on an odd-numbered day,
      and they received a photocopied photograph of the hospital. One hundred thirteen
      children were assigned to the intervention group, and they received a personal
      counseling session and signed a contract promising to wear their bicycle helmets.
      In addition, 57 of the intervention children were assigned (based on having an
      even-numbered birthday) to be fitted with helmets if they did not already own
      them. Parents were telephoned four weeks after the ED encounter for follow-up.
      RESULTS: Follow-up data were obtained for 148 children (67% follow-up rate), of
      whom only 69 reported riding a bicycle in the four weeks after their ED visit. Of
      the final sample of 69 children, 38 belonged to one of the intervention groups,
      and 25 of these (66%) reported always wearing a helmet while cycling during the
      four weeks after their ED visit, versus 13 of 31 (42%) in the control group (odds
      ratio, 2.66; p < 0.05). The effect of the intervention was independent of whether
      the children owned a helmet at baseline. CONCLUSIONS: Injury prevention
      counseling in the ED using "The Injury Prevention Program" (TIPP) sheet,
      behavioral contracting, and helmet distribution may have a significant effect on
      reports of subsequent bike helmet use.

PMID- 14644791
TI  - Anogenital injuries in adolescents after consensual sexual intercourse.
AB  - OBJECTIVES: To compare the types and locations of anogenital injuries occurring
      in adolescent females (13-17 years old) after consensual and nonconsensual sexual
      intercourse. METHODS: The authors conducted a retrospective, matched case-control
      study to assess anogenital injuries in female adolescents presenting to a free
      standing nurse examiner clinic during a four-year study period. Adolescents were
      selected for inclusion in the study if they reported consensual sexual
      intercourse (CSI) and agreed to a medical-legal examination. Control subjects
      were victims of alleged sexual assault or nonconsensual sexual intercourse (NCSI)
      matched to cases by age and prior sexual intercourse experience. Genital trauma
      was documented using colposcopy with nuclear staining and digital photography.
      Data were analyzed using chi-square and t-tests. RESULTS: Fifty-one cases of CSI
      were identified; the age range was 13 to 17 years (mean=15.1 years). Overall, 49%
      (25/51) of CSI subjects reported no prior sexual intercourse experience. CSI and
      NCSI were comparable in terms of race, time to physical examination, alcohol use,
      and frequency of genital injuries (73% vs. 85%, p=0.069). The mean number of
      documented anogenital injuries in CSI subjects was 1.9 +/- 1.5. These injuries
      commonly involved the hymen, fossa navicularis, and posterior fourchette. CSI
      subjects had a greater number of anogenital injuries (2.6 +/- 2.0; p=0.02),
      typically involving the fossa navicularis, labia minora, and hymen. The most
      common type of injury in both groups was lacerations (39% vs. 41%); however, NCSI
      subjects had a greater incidence of anogenital abrasions, ecchymosis, and edema
      (chi2=10.4, p=0.035). CONCLUSIONS: Anogenital trauma was documented in 73% of
      adolescent females after consensual sexual intercourse versus 85% of victims of
      sexual assault. The localized pattern and severity of anogenital injuries were
      significantly different when compared with victims of sexual assault.

PMID- 14644792
TI  - Clinicopathological conference: A case of more than a sprained ankle.

PMID- 14644793
TI  - Bedside diagnosis of vertigo: value of the history and neurological examination.
AB  - Vertigo is caused by disturbance of the input or central processing of sensory
      signals from the vestibular apparatus that provide information regarding the
      position of the body in space. It is caused either by asymmetric disruption of
      sensory input from the vestibular organs or asymmetric integration of vestibular
      input into the central nervous system. Vertigo is readily differentiated from
      other causes of dizziness by a sensation of motion. A crucial aspect of the
      management of the emergency department patient with vertigo is the
      differentiation of vertigo associated with acute stroke syndromes from vertigo
      due to peripheral causes. Routine computerized axial tomography imaging is
      insensitive for posterior circulation strokes, so for emergency physicians, the
      history and neurological examination remain the most useful diagnostic tools.
      This article emphasizes the history and physical examination in the localization
      of the lesion in patients with vertigo and offers a rational basis for decisions
      regarding the need for special neurological imaging and consultation. It also
      emphasizes subtle findings that may prevent the erroneous diagnosis of peripheral
      vertigo in the presence of an acute stroke syndrome.

PMID- 14644794
TI  - Treatment of acute stroke with recombinant tissue plasminogen activator and
      abciximab.
AB  - OBJECTIVES: Preclinical data suggest that treatment of acute ischemic stroke
      (AIS) with the combination of recombinant tissue plasminogen activator (rt-PA)
      and abciximab may increase efficacy and decrease the rate of symptomatic
      intracranial hemorrhage (sICH). The authors report pilot data of five AIS
      patients with half-dose rt-PA and abciximab as part of an ongoing phase I safety
      trial with sICH as the primary outcome. METHODS: Five patients with AIS were
      treated with the combination of half-dose rt-PA (0.45 mg/kg) and abciximab (0.25
      mg/kg bolus followed by a 0.125 microg/kg/min infusion over 12 hours). Head
      computed tomographic scan was obtained after 24 hours of treatment onset.
      RESULTS: Four patients received the combination of half-dose abciximab and rt-PA
      without major complications. One patient experienced a parenchymal hematoma type
      1 ICH without significant decline of his neurological status. The average
      National Institutes of Health Stroke Scale change at discharge in comparison with
      pretreatment was -5.4 +/- 7.0, and the median change was 6 points with a range of
      4 points (worsening) to -13 points (improvement) (p=0.07) based on a one-sided t
      test. CONCLUSIONS: Administration of rt-PA and abciximab to AIS patients was
      completed without difficulty. No sICH were observed; however, 20% (1 out of 5)
      experienced an asymptomatic ICH. Based on our observation of five patients, there
      was a trend of treatment efficacy; however, these results need to be confirmed in
      a larger-scale placebo-controlled clinical trial.

PMID- 14644795
TI  - Influenza a in young children with suspected respiratory syncytial virus
      infection.
AB  - OBJECTIVES: To determine the prevalence of influenza A in young children
      suspected of having respiratory syncytial virus (RSV) infection and to compare
      the clinical presentation of these patients with those who have proven RSV
      infection. METHODS: Children younger than or at 36 months of age who presented to
      a pediatric emergency department (ED) with suspected RSV infection during the
      influenza A season of 2001-2002 were eligible. Eligible children had an RSV
      antigen test ordered as part of their initial clinical management. A consecutive
      sample of children was enrolled for prospective observational analysis. The main
      outcome measure was the prevalence of influenza A in young children with
      suspected RSV infection. The secondary outcome measure was a comparison of the
      clinical presentations, of the two groups. RESULTS: During the study period, 420
      patients presented for evaluation of respiratory illness. RSV tests were ordered
      on 251 patients. Of 197 eligible patients, 124 (63%) tested positive for RSV and
      33 (17%) for influenza A. Influenza A patients were more likely to have
      temperatures at or above 39 degrees C than RSV patients (36% vs. 15%; p = 0.01).
      RSV patients were more tachypneic (54 vs. 43 breaths/minute; p < 0.0001) and more
      often had wheezing (90% vs. 8%; p < 0.0001). Twenty influenza patients (61%) were
      hospitalized. CONCLUSIONS: This study found a high prevalence of influenza A in
      young children suspected of having RSV infection. Clinicians should consider
      influenza A in young febrile children presenting with respiratory illnesses.

PMID- 14644796
TI  - Training of residents for their role as flight physicians: a survey of emergency
      medicine training programs.
AB  - OBJECTIVE: To determine the number of emergency medicine (EM) residency programs
      in which residents serve as helicopter emergency medical services (HEMS) crew,
      the extent of training provided for this role, and how HEMS residents are
      evaluated. METHODS: Accredited EM residency programs were contacted by telephone
      to determine which programs had residents serving as HEMS physicians. A self
      administered survey was then mailed to the medical directors of the HEMS
      programs. Descriptive statistics were determined for each question. RESULTS:
      Surveys were returned by 18 of the 20 residency programs (90%) where residents
      served as HEMS physicians. In the majority (94%), residents work with one other
      crew member, typically a nurse or paramedic. The amount of flight hours for a
      resident ranged from 25 to 500. The number of flights ranged from five to 225.
      The amount of HEMS training was highly variable. Four programs (22%) did not
      require any orientation flights with patients; 12 (67%) did not require any
      proficiency testing; direct attending supervision was rare (6%); and written
      feedback occurred in only 28% of programs. CONCLUSIONS: The training of residents
      for their role as flight physicians is highly variable, considering the amount of
      air transport time they perform. Direct faculty supervision, proficiency testing,
      and written feedback are rarely utilized.

PMID- 14644797
TI  - Intraosseous emergency access by physicians wearing full protective gear.
AB  - OBJECTIVES: To assess prospectively and randomly the feasibility, speed, and
      success rate of establishing an intraosseous access using the Bone Injection Gun
      (BIG) while wearing antichemical outfits. METHODS: Attempts to introduce
      intraosseous injection with or without a full protective gear (antichemical body
      suit, face mask, and butyl gloves) were performed using a turkey bone model. Time
      to proper placement was measured. RESULTS: The average time to successfully
      insert the BIG's needle while wearing a protective gear was 32 +/- 3 seconds
      compared with 22 +/- 2 seconds (p<0.05) without the outfit. Success rate was
      greater than or equal to 80%. When failure occurred, a second attempt always
      proved successful. CONCLUSIONS: The intraosseous insertion of the BIG's needle is
      rapid and easy but requires 50% more time when wearing protective gear than
      without it. Its use during emergent treatment of toxic mass casualty is of
      potential benefit and needs further investigation.

PMID- 14644799
TI  - Satellite and mobile wireless transmission of focused assessment with sonography
      in trauma.
AB  - OBJECTIVES: Focused assessment with sonography in trauma (FAST) can define life
      threatening injuries in austere settings with remote real-time review by
      experienced physicians. This study evaluates vest-mounted microwave, satellite,
      and LifeLink communications technology for image clarity and diagnostic accuracy
      during remote transmission of FAST examinations. METHODS: Using a SonoSite, FAST
      was obtained on three patients with pericardial and intraperitoneal effusions and
      two control subjects in a remotely located U.S. Army Combat Support Hospital. A
      miniature vest-mounted video transmitter attached to the SonoSite sent wireless
      ultrasound video 20 m to a receiving antenna. The signal was then transferred
      over VSAT satellite systems at 512 kilobaud per second (kbps), INMARSAT satellite
      systems at 64 kbps, and over LifeLink on a moving ambulance through a
      metropolitan wireless traffic-management network. Clarity and absence or presence
      of effusions were recorded by 15 staff emergency physicians. RESULTS: Average
      sensitivity, specificity, and accuracy were 87% (95% confidence interval [CI]=79%
      to 95%), 85% (95% CI=81% to 89%), and 86% (95% CI=82% to 90%) for the Premier
      Wireless Vest; 98% (95% CI=97% to 99%), 83% (95% CI=75% to 91%), and 86% (95%
      CI=82% to 90%) for VSAT; 95% (95% CI=94% to 96%), 70% (95% CI=58% to 82%), and
      75% (95% CI=70% to 80%) for INMARSAT; and 82% (95% CI=73% to 91%), 83% (95%
      CI=74% to 92%), and 82% (95% CI=78% to 86%) for LifeLink with clarity of 3.0 (95%
      CI=2.7 to 3.3), 2.9 (95% CI=2.6 to 3.2), 1.3 (95% CI=1.2 to 1.4), and 2.1 (95%
      CI=1.8 to 2.4), respectively. CONCLUSIONS: Accuracy correlated with clarity.
      Roaming vest transmission of FAST provides interpretable, diagnostic imagery at
      the distances used in this study. VSAT provided the best clarity and diagnostic
      value with the lighter, more portable INMARSAT serving a lesser role for remote
      clinical interpretation. LifeLink performed well, and further infrastructure
      improvements may increase clarity and accuracy.

PMID- 14644801
TI  - Emergency medicine advertisement paradox.

PMID- 14644800
TI  - Emergency department HIV testing: sounds good, but...?

PMID- 14644803
TI  - Foreword.

PMID- 14644804
TI  - Reproductive health and obstetricians and gynecologists.
AB  - The art of medicine provides a rare opportunity to understand human values and to
      contribute toward the well-being of one's fellow humans--women in the case of ob
      gyn--a contribution that fits in with the mission of the International Federation
      of Gynaecology Obstetrics (FIGO). Obstetricians and gynecologists should indeed
      take it upon themselves to improve conditions for women, since the bond and
      respect between the two is a significant one. It is obstetricians-gynecologists
      who can provide the much needed technical information to throw light on
      justifying services that deal with devastating, debilitating, degenerating, and
      devaluating situations, such as neglected pregnancy, disregard toward cancer
      detection, and humiliating genital mutilation. Indeed, this can be termed as
      "terrorism in ob-gyn," neglected by those who should deal with it. Those in ob
      gyn and other medical professions clearly witness gender inequality and its ugly
      aftermath, a degradation of women's reproductive rights. Ob-gyn must look a
      little beyond just the lucrative practice of the plain science of obstetrics and
      gynecology and undertake the responsibility to help and protect the health and
      life of women around the world. A conscientious doctor cannot practice medicine
      on women's bodies alone, but must also "practice" against several social evils,
      the prevention of which is crucial to women's health. Obstetricians and
      gynecologists can utilize their access to policymakers and health "builders" to
      carry this brief for women's health, and can urge governments to take a second
      look at women's rights to ensure that they are on par with the accepted norms of
      human rights, to be protected and propagated.

PMID- 14644805
TI  - Ethical aspects of advanced reproductive technologies.
AB  - The progress achieved during the last 25 years in the assisted reproductive
      technology field has been phenomenal. Many countries currently practice genetic
      material donation, human embryo cryopreservation, selective embryo reduction,
      preimplantation genetic diagnosis, and surrogacy. While embryo research and
      therapeutic cloning are carried out only in a few centers, thus far human cloning
      has been universally condemned. Nonetheless, the rapid evolution and progress of
      these various techniques of assisted reproduction has opened a Pandora's box of
      ethical issues that must be urgently addressed.

PMID- 14644806
TI  - Molecular abnormalities of FSH and LH action.
AB  - The identification of naturally occurring genetic mutations in individuals with
      disorders of reproductive function is the first logical step to therapy. To date,
      diagnostic investigations have been assisted by polymerase chain reaction and the
      development of an increasing number of effective screening techniques to scan
      genomic DNA (deoxyribonucleic acid) for causative mutations. The continued
      expansion of these technologies, coupled with high throughput gene sequencing,
      will ultimately result in automated DNA diagnosis for the practicing clinician at
      the point of care. At that time, the direct examination of a patient's DNA will
      be the definitive means of establishing the presence of specific genetic changes
      that cause or increase one's susceptibility to disease. This presentation selects
      important candidate genes in the human hypothalamic-pituitary-ovarian axis (HPG),
      reviews our knowledge of the spontaneously occurring human mutations that affect
      these genes, and reviews the biological implications of this information. To
      date, causative mutations in candidate genes have provided important insights
      into the transcription factors, receptors, and hormones that regulate the HPG
      axis at many levels. A major challenge in this field is that mutations in many of
      these genes and others remaining to be identified lead to infertility. The
      reduction in reproductive fitness due to these mutations limits the ability of
      investigators to use traditional genetic linkage and association studies to
      identify and clone important unidentified reproductive genes. Fortunately
      analysis of human gametes and new strategies that are being developed for the
      identification and mapping of complex human diseases will become increasingly
      important in continuing studies of idiopathic human infertility. At this time, it
      is helpful for the reader to become acquainted with some of the prototype
      mutations in candidate genes, their phenotypic consequences, and their
      prevalence. This presentation is designed to describe the known mutations in the
      gonadotropin genes and the genes encoding their respective receptors. The
      phenotypic effects of these mutations is compared, and evidence for causation is
      reviewed.

PMID- 14644807
TI  - Modulatory effect of the ovary on LH secretion.
AB  - Ovarian steroids are important regulators of gonadotropin secretion during the
      normal menstrual cycle. Estradiol is the predominant factor in the follicular
      phase, while progesterone plays an important role in the luteal phase.
      Gonadotropin surge attenuating factor (GnSAF) is a nonsteroidal ovarian substance
      that attenuates the endogenous LH surge in superovulated women. Attempts to
      purify GnSAF from various sources have provided several sequences. In human
      follicular fluid, GnSAF is shown to be the carboxyl terminal fragment of human
      serum albumin (HSA) and a molecular mass of 12.5 kDa. Preliminary data have shown
      the expression of the carboxyl terminal fragment of HSA in human granulosa cells.
      In vivo studies have provided evidence that GnSAF may participate in the control
      of LH response to GnRH in the context of a mechanism that facilitates the full
      expression of the midcycle LH surge. Further research is expected to clarify the
      role of GnSAF in women's physiology.

PMID- 14644808
TI  - Some new thoughts on the pathophysiology and genetics of polycystic ovary
      syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder of unknown etiology, but
      several lines of evidence suggest that there is an underlying genetic cause for
      PCOS. Studies of first-degree relatives of women diagnosed with PCOS reveal
      familial clustering of the disease, particularly hyperandrogenemia. A prospective
      study of first-degree female relatives of PCOS women found that 46% of
      ascertainable sisters of PCOS women were hyperandrogenemic. The serum
      bioavailable testosterone in the cohort of sisters showed a bimodal distribution.
      These observations suggest a dominantly inherited trait controlling androgen
      levels. Studies on cultures of human theca cells derived from follicles isolated
      from the ovaries of PCOS and normal women demonstrated that PCOS theca cells
      produce greater amounts of testosterone, 17alpha-hydroxyprogesterone, and
      progesterone than normal theca cells, despite the fact that cells were cultured
      under identical conditions for multiple population doublings. Examination of the
      metabolism of radiolabeled steroid hormone precursors and steady-state levels of
      mRNAs encoding steroidogenic enzymes revealed that there are multiple alterations
      in the steroidogenic machinery of PCOS theca cells, including elevated expression
      of the CYP11A, 3BHSD2, and CYP17 genes. The increased mRNA levels are the result,
      in least in part, of increased gene transcription. Interestingly, the STAR gene
      is not expressed at a higher level in PCOS theca cells. The stable up-regulation
      of steroidogenesis in PCOS thecal cells indicates either a genetic abnormality in
      these cells or a persistent metabolic imprint established in vivo. Linkage and
      association studies conducted by the National Cooperative Program in Infertility
      Research using affected sib-pair analysis and the transmission/disequilibrium
      test to explore candidate genes point a finger at a region on chromosome 19p13.3.
      The putative PCOS gene lying in this region has yet to be identified. However,
      existing data suggest that it is probably involved in signal transduction
      mechanisms leading to altered expression of a suite of genes that affect theca
      cell steroidogenic activity as well as the metabolic phenotype of other cell
      types, including muscle and fat.

PMID- 14644809
TI  - Polycystic ovary syndrome in adolescence.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder among reproductive-age
      women, yet the diagnosis may be overlooked during adolescence. Although the
      clinical and metabolic features are similar to those found in adult women, it can
      be difficult to distinguish the young woman with PCOS from a normal adolescent.
      Irregular menses, anovulatory cycles, and acne are not uncommon in adolescent
      women. Adolescents with a history of premature pubarche, a family history of
      PCOS, Caribbean-Hispanic and African-American ancestry, and/or obesity are at
      risk for PCOS and deserve close surveillance. The laboratory evaluation of the
      adolescent with suspected PCOS or hyperandrogenism should be individualized based
      on the history, symptoms, and examination findings. The cornerstone of management
      of PCOS in adolescence includes either a combination oral contraceptive or
      progestin. Consideration of insulin-sensitizing agents, antiandrogens, topical
      treatments for acne, and various treatments for hair removal are dependent on the
      patient's symptoms and concerns. Healthy eating, regular exercise, and for the
      overweight adolescent, weight reduction, are encouraged to reduce the risk of
      cardiovascular disease and type II diabetes mellitus. Numerous studies have shown
      that weight loss and exercise decrease androgen levels, improve insulin
      sensitivity, and lead to the resumption of ovulation. Although initial studies
      suggest that Metformin may be particularly useful for treating the PCOS
      adolescent with insulin resistance and obesity, additional studies are needed to
      determine the efficacy and long-term outcome. Management of the adolescent with
      PCOS is challenging and requires a supportive, multidisciplinary team approach
      for optimal results.

PMID- 14644810
TI  - Interactions of leptin, GH, and cortisol in normal children.
AB  - Leptin is the product of the ob gene located in humans on chromosome 7q31.3. It
      is a 16-kDa protein named after the Greek "leptos," meaning lean, to indicate the
      function that this adipocyte-secreted protein was thought to have. Since its
      discovery, in fact, most of the research focused on the role of leptin in body
      weight regulation, aiming to elucidate the pathophysiology of human obesity.
      However, more and more data show that leptin is not only important in the
      regulation of food intake and energy balance, but it also functions as a
      neuroendocrine hormone. It is involved in glucose metabolism, as well as in
      normal sexual maturation and reproduction, and interacts with the hypothalamic
      pituitary-adrenal (HPA) and the growth hormone (GH) axes.

PMID- 14644811
TI  - The role of leptin in female adolescence.
AB  - Leptin, the ob gene product, is related to the onset of puberty in animal models,
      but its role in human puberty is still rather undefined. In prepubertal girls and
      boys, leptin concentrations increase slowly with age and body-fat mass. In boys,
      this increase is interrupted in early puberty, when testosterone and lean body
      mass increase. In girls, leptin, along with the body-fat mass, continue to
      increase during puberty. Plasma leptin concentrations are significantly
      correlated with fat mass at all Tanner stages in males and females. The diurnal
      variation of leptin concentrations seen in adults is apparent for all age groups
      with no significant changes in the pattern across puberty. Leptin is bound in
      blood by a high-affinity binding protein identical with the soluble leptin
      receptor (sOB-R). In the first year of life, the concentration of sOB-R is high,
      and then a continuous decline of sOB-R follows until midpuberty. The therapeutic
      response to leptin treatment in a child with leptin deficiency confirms the
      importance of leptin in the regulation of body weight in humans, and establishes
      an important role for this hormone in the regulation of appetite. Still no
      evidence is available that would indicate leptin is a primary signal that
      initiates the onset of human puberty. Instead, it may act in a permissive way as
      one of several metabolic factors to allow pubertal maturation to proceed and
      later reproduction to occur.

PMID- 14644812
TI  - Growth hormone insufficiency and its impact on ovarian function.
AB  - Growth hormone (GH) and the insulin-like growth factor-I (IGF-I) play significant
      roles in pubertal development, menarche, the menstrual cycle, fertility, and
      reproduction. Growth hormone deficiency or insufficiency causes a delay in the
      onset of puberty and in its normal course unless treated with synthetic GH. It
      seems that GH affects the ovary during puberty both indirectly through the
      gonadotropins and IGF-I, and directly through its effect on steroidogenesis. The
      GH axis is activated by small increases in circulating estrogens, which initiate
      large increases in GH during puberty. The reproductive function of the female is
      also affected by GH. GH acts on the ovary affecting gametogenesis and
      steroidogenesis. GH receptor mRNA and protein have been found in ovarian cells,
      and this suggests that the direct action of GH provides an important modulatory
      effect on gonadotropin-dependent and -independent functions. It also affects the
      maturation of the follicle and gamete, and thereby plays a facilitatory role in
      fertility. The majority of women with GH-deficiency, but not all, require
      assisted reproductive technologies to induce ovulation. Many women with
      polycystic ovary syndrome (PCOS) have an impaired GH response to stimulation with
      Levo-Dopa and GH releasing hormone (GHRH). Hyperandrogenism in PCOS may
      contribute to the reduced GH secretion because testosterone directly stimulates
      somatostatin release. Reduction of the excessive androgens facilitates the
      dopaminergic control of GH. In conclusion, GH-insufficient states disrupt ovarian
      function, causing problems in sexual maturation, the menstrual cycle, and the
      reproductive ability of the female.

PMID- 14644813
TI  - Uterine and embryonic trophoblast CRH promotes implantation and maintenance of
      early pregnancy.
AB  - Epithelial cells of human endometrium and differentiated endometrial stromal
      cells express the corticotropin-releasing hormone (CRH) gene. CRH is also
      produced by the human placental cytotrophoblast. Endometrial and placental CRH is
      under the endocrine control of gonadal steroids as well as under an
      autocrine/paracrine regulation by prostanoids and interleukins. Human
      endometrium, myometrium and placenta also express the relevant receptors.
      Invasive trophoblasts promote apoptosis of activated Fas-expressing human T
      lymphocytes, an effect potentiated by CRH and inhibited by the CRH type 1
      antagonist, antalarmin. Female rats treated with antalarmin during the first 6
      days of gestation had a dose-dependent decrease of implantation sites and live
      embryos, and significantly decreased endometrial FasL expression. Our data
      suggest important physiological roles of endometrial and placental CRH in the
      regulation of decidualization, blastocyst implantation, and early maternal
      tolerance.

PMID- 14644814
TI  - Perimenopausal conception.
AB  - Fertility, defined as the ability to achieve a pregnancy, declines gradually over
      the woman's lifespan. Although this decline seems to begin from the age of 30
      years, it is more obvious between 35 and 40 and increases dramatically
      thereafter. The age of 41 is considered to be the point when fertility stops and
      sterility starts. The actual menopause occurs approximately 10 years after the
      substantial loss of conception potential. Thus, the biological rather than the
      chronological age of the woman can predict more accurately her fertility
      potential. This decline in female reproductive potential correlates with ovarian
      factors, although a slight contribution from the uterus itself and from the
      neuroendocrine axis cannot be excluded. The ovarian reserve decreases with
      advancing age, while a parallel decrease in the quality of the oocytes is
      present, as indicated by the increased incidence of oocyte aneuploidy. The
      endocrine function of the ovary also declines with age, the later becoming unable
      to sustain its normal function in the neuroendocrine axis. Additionally, the role
      of the various endometrial factors remains controversial. On the other hand,
      exposure to toxic factors and the increased prevalence of infertility-related
      diseases like endometriosis and PID, may also contribute. Spontaneous conception
      rates are minimal in perimenopausal women, mainly due to a qualitative and
      quantitative loss of female gametes. In the rare case of spontaneous conception
      achievement, complications are more likely. The application of classic ovulation
      induction and IVF may serve some selected cases, where the woman's ovarian
      biological age does not correspond to her chronological one. However, the
      implantation, clinical pregnancy, and live birth rates in women of advanced age
      undergoing IVF treatment, show very poor results. On the other hand,
      preimplantation genetic diagnosis is an accurate diagnostic tool for exclusion of
      genetically deficient embryos prior to embryo transfer. Oocyte donation seems to
      be the most reliable option of the perimenopausal woman, since the cumulative
      birth rates after four treatment cycles is approximately 80%. Cryopreservation of
      ovarian tissue may be an alternative in nulliparas women <40 years of age who
      want to have children in the future or women with the same desire who,
      unfortunately, have had pelvic radiotherapy, chemotherapy, oophorectomy, or
      premature menopause. This technique has given encouraging results in animals, but
      has not achieved pregnancies in humans. In the future, the use of drugs to block
      oocyte depletion as well as recent techniques, such as cytoplasmic or germinal
      vesicle transfer, will be more widely tested and may offer an option to the
      perimenopausal woman who wishes to conceive.

PMID- 14644815
TI  - Mild stimulation in in vitro fertilization.
AB  - Current approaches to ovarian stimulation for in vitro fertilization (IVF) are
      aimed at optimizing the number of oocytes retrieved in a treatment cycle. This
      approach is not without risks. Moreover, as the true costs of multiple pregnancy
      become clearer, the need to produce multiple embryos for transfer is increasingly
      questioned. Increasing knowledge of the physiological mechanisms involved in
      follicular development and dominance has led to new strategies in ovarian
      stimulation for IVF. The clinical availability of GnRH antagonists allows the
      normal cycle to be harnessed and manipulated by mild interventions to produce
      sufficient oocytes for successful IVF treatment. Recent evidence suggests that
      oocyte quality after mild stimulation may be superior to that after conventional
      stimulation regimens.

PMID- 14644816
TI  - Alternative approaches in the management of poor response in controlled ovarian
      hyperstimulation (COH).
AB  - Improving pregnancy rates in patients with many failed attempts remains a
      challenge during IVF-ET or ICSI-ET programs. The availability of good-quality
      oocytes is a prerequisite for good results in such programs. The use of a
      personalized protocol for controlled ovarian hyperstimulation (COH) that gives
      the best possible results for the specific patient is a main factor for the
      success in IVF or ICSI. The response of many patients to the ovarian stimulation
      used is very poor, giving fewer oocytes than expected, resulting in much lower,
      if any, pregnancy rates. The definition of a poor responder is not clear and
      differs among researchers. A variety of strategies have been used to improve
      response in these patients, regardless of the definition used. These include
      various ovulation induction protocols that we believe might assist these patients
      achieve a pregnancy. The difficulty is greater due to the fact that poor
      responders are not a homogeneous group and each patient may have a different
      cause. More studies with large numbers of patients are needed in order to find
      those protocols that could provide these couples with an acceptable pregnancy
      rate.

PMID- 14644817
TI  - Endometrial pinopodes and uterine receptivity.
AB  - The human endometrium is an extremely sensitive target for steroid hormones.
      During the menstrual cycle, this tissue undergoes dynamic changes which are
      reflected on the surface morphology of the epithelium, and which can be followed
      by scanning electron microscopy. The morphological changes peak at the
      midsecretory phase, with the formation of the so-called pinopodes. Increasing
      evidence suggests that these pinopodes are accurate markers for endometrial
      receptivity, and their detection may be of high clinical utility for the
      preparation of endometrium before embryo transfer.

PMID- 14644818
TI  - In vitro fertilization: angiogenic, proliferative, and apoptotic factors in the
      follicular fluid.
AB  - The studies reported investigated the concentrations of angiogenic,
      proliferative, and apoptotic factors in the follicular fluid (FF) of individual
      follicles, aspirated from women undergoing controlled ovarian hyperstimulation
      using a long protocol for IVF treatment. Furthermore, the association of the
      concentrations of the preceding factors with oocyte maturity was studied.
      Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      angiogenin, tissue polypeptide specific antigen (TPS), and soluble Fas (sFas)
      were all found in the FF of all follicles examined. Moreover, from the angiogenic
      factors only angiogenin concentrations, and from the apoptotic factors sFas
      concentrations (the soluble form expressing rather an antiapoptotic function),
      were positively associated with oocyte maturity, possibly indicating angiogenin's
      biological role beyond neovascularization and a lower apoptotic rate allowing
      oocytes to mature. Last, the abundant expression of TPS in FF may be indicative
      of intense cell proliferation, in cases of ovarian stimulation.

PMID- 14644819
TI  - Roles of reproductive corticotropin-releasing hormone.
AB  - Corticotropin-releasing hormone (CRH), the principal regulator of the
      hypothalamic-pituitary-adrenal axis, as well as its receptors, have been
      identified in most female reproductive tissues, including the uterus, placenta,
      and ovary. Endometrial CRH may participate in decidualization, implantation, and
      early maternal tolerance; placental CRH may participate in the physiology of
      pregnancy and the onset of parturition, and ovarian CRH may participate in
      follicular maturation, ovulation, and luteolysis. The hypercortisolism of the
      latter half of pregnancy can be explained by increased levels of placental CRH in
      plasma. This hypercortisolism is followed by a transient suppression of
      hypothalamic CRH secretion in the postpartum period, which may explain the blues
      or depression and autoimmune phenomena frequently observed during this period.

PMID- 14644820
TI  - Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and
      postpartum.
AB  - The principal modulators of the hypothalamic-pituitary-adrenal (HPA) axis are
      corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP).
      Corticotropin-releasing hormone is not exclusively produced in the hypothalamus.
      Its presence has been demonstrated at peripheral inflammatory sites. Ovulation
      and luteolysis bear characteristics of an aseptic inflammation. CRH was found in
      the theca and stromal cells as well as in cells of the corpora lutea of human and
      rat ovaries. The cytoplasm of the glandular epithelial cells of the endometrium
      has been shown to contain CRH and the myometrium contains specific CRH receptors.
      It has been suggested that CRH of fetal and maternal origin regulates FasL
      production, thus affecting the invasion (implantation) process through a local
      auto-paracrine regulatory loop involving the cytotrophoblast cells. Thus, the
      latter may regulate their own apoptosis. During pregnancy, the plasma level of
      circulating maternal immunoreactive CRH increases exponentially from the first
      trimester of gestation due to the CRH production in the placenta, decidua, and
      fetal membranes. The presence in plasma and amniotic fluid of a CRH-binding
      protein (CRHbp) that reduces the bioactivity of circulating CRH by binding is
      unique to humans. Maternal pituitary ACTH secretion and plasma ACTH levels rise
      during pregnancy-though remaining within normal limits-paralleling the rise of
      plasma cortisol levels. The maternal adrenal glands during pregnancy gradually
      become hypertrophic. Pregnancy is a transient, but physiologic, period of
      hypercortisolism. The diurnal variation of plasma cortisol levels is maintained
      in pregnancy, probably due to the secretion of AVP from the parvicellular
      paraventricular nuclei. CRH is detected in the fetal hypothalamus as early as the
      12th week of gestation. CRH levels in fetal plasma are 50% less than in maternal
      plasma. The circulating fetal CRH is almost exclusively of placental origin. The
      placenta secretes CRH at a slower rate in the fetal compartment. AVP is detected
      in some neurons of the fetal hypothalamus together with CRH. AVP is usually
      detectable in the human fetal neurohypophysis at 11 to 12 weeks gestation and
      increases over 1000-fold over the next 12 to 16 weeks. The role of fetal AVP is
      unclear. Labor appears to be a stimulus for AVP release by the fetus. The
      processing of POMC differs in the anterior and intermediate lobes of the fetal
      pituitary gland. Corticotropin (ACTH) is detectable by radioimmunoassay in fetal
      plasma at 12 weeks gestation. Concentrations are higher before 34 weeks
      gestation, with a significant fall in late gestation. The human fetal adrenal is
      enormous relative to that of the adult organ. Adrenal steroid synthesis is
      increased in the fetus. The major steroid produced by the fetal adrenal zone is
      sulfoconjugated dehydroepiandrosterone (DHEAS). The majority of cortisol present
      in the fetal circulation appears to be of maternal origin, at least in the
      nonhuman primate. The fetal adrenal uses the large amounts of progesterone
      supplied by the placenta to make cortisol. Another source of cortisol for the
      fetus is the amniotic fluid where cortisol converted from cortisone by the
      choriodecidua, is found. In humans, maternal plasma CRH, ACTH, and cortisol
      levels increase during normal labor and drop at about four days postpartum;
      however, maternal ACTH and cortisol levels at this stage are not correlated. In
      sheep, placental CRH stimulates the fetal production of ACTH, which in turn leads
      to a surge of fetal cortisol secretion that precipitates parturition. The 10-day
      long intravenous administration of antalarmin, a CRH receptor antagonist,
      significantly prolonged gestation compared to the control group of animals. Thus,
      CRH receptor antagonism in the fetus can also delay parturition. The HPA axis
      during the postpartum period gradually recovers from its activated state during
      pregnancy. The adrenals are mildly suppressed in a way analogous to postcure
      Cushing's syndrome. Provocation testing has shown that hypothalamic CRH secretion
      is transiently suppriently suppressed at three and six weeks postpartum,
      normalizing at 12 weeks.

PMID- 14644821
TI  - Endocrine-related causes and consequences of intrauterine growth retardation.
AB  - The term intrauterine growth retardation (IUGR) is assigned to newborns born with
      a birth weight and/or birth length below the tenth percentile for their
      gestational age. Intrauterine growth retardation is usually due to maternal,
      fetal factors, or placental insufficiency, while endocrine factors represent just
      a small minority in its etiology. Main endocrine-related causes of IUGR are
      disorders in insulin or insulin-like growth factor-I (IGF-I) secretion or action.
      Newborns with IUGR are at increased risk to develop a metabolic syndrome later in
      life, namely obesity, arterial hypertension, hypercholesterolemia, cardiovascular
      disease, impaired glucose tolerance, or diabetes mellitus type 2. This
      association is the result of the adaptational changes of the fetal endocrine
      metabolic mechanisms to the impaired intrauterine milieu to assure survival in
      the short term. The persistence of these changes after birth can be detrimental
      in adult life. Furthermore, premature adrenarche, as well as ovarian
      hyperandrogenism, seem to be associated with IUGR in girls, demonstrating that
      IUGR may have long-lasting effects on both somatic health and reproductive
      function. Finally, the intrauterine exposure of the fetus to stressors may affect
      the individual's ability to face stress in postnatal life. Therefore, if
      optimization of somatic and psychosocial well-being of the individual is the
      golden goal of medicine, special attention should be paid to maintain an optimal
      intrauterine milieu devoid of any stressors with adequate nutrient supply and to
      reserve ideal psychosocial support to the pregnant woman.

PMID- 14644822
TI  - How low can you get?
AB  - Since the early 1960s the side effects of oral contraceptives have been known to
      be related to the high doses (50 micro g) of ethinyl estradiol used. Research has
      focused on reducing the dose of both the estrogen and progestin components to
      reduce these side effects. While reducing the dose of both components, the
      contraceptive efficacy has to be maintained so as to retain a satisfactory Pearl
      index. These requirements appear to have been attained with 24-day regimen of a
      low-dose pill (15 microg of ethinyl estradiol and 60 microg of gestedone) as one
      part of an open-label noncomparative multicenter study. This paper reports our
      unit's results, which indicate that the low-dose pill promises to reduce
      contraceptive-related side effects, to encourage better compliance, and as
      corollary, to retain a satisfactory Pearl index.

PMID- 14644823
TI  - Seventy-five microgram desogestrel minipill, a new perspective in estrogen-free
      contraception.
AB  - Progestin-only minipills have been available for over three decades, yet their
      use has been limited, because of a documented lower efficacy when compared to
      pills that combine estrogen and progestin. The availability of a new low-dose
      progestin-only minipill containing 75 microg desogestrel (DSG) offers a new
      perspective, since, in a large multicenter study, this minipill gave a crude
      Pearl index of 0.41 and an adjusted one of 0.14, which is comparable to indices
      found in clinical trials of oral contraceptives. This minipill also allows for a
      12-hour tolerance time in taking the pill. The high effectiveness of the DSG
      minipill is attributable to an almost constant inhibition of ovulation, as shown
      by the absence of elevated progesterone circulating levels and inhibition of
      follicular growth in the vast majority of cycles studied. Since irregular
      bleeding patterns are observed with all minipills, patterns experienced with DSG
      75 microg have been compared to those obtained with levonogestrel 30 microg. As
      expected, the more pronounced ovarian inhibition produced wider bleeding
      variability with DSG, but also less bleeding overall. The DSG minipill is
      suitable for lactating women and represents a valuable addition to oral
      contraception.

PMID- 14644824
TI  - Miniature, low-dose, intrauterine drug-delivery systems.
AB  - The safety of systemically administered sex steroids continues to be a major
      focus of researchers. The negative results of the Women's Health Initiative study
      (WHI), and follow-up reports published in JAMA, evaluating the safety of estro
      progestogen in postmenopausal women, elicited an unprecedented reaction in the
      press by women and doctors alike. From these publications, it is clear that
      research should focus on new progestogens and on alternative administration
      routes to minimize adverse drug effects. One approach to the improvement of
      safety, efficacy, and acceptability of steroid hormones, including patient
      compliance, is to develop long-acting implantable methods that deliver the lowest
      possible dose to the key target tissues. This therapeutic concept of "minimal
      intervention" has been known for several decades, but the practical applications
      of the method were lacking. Intrauterine drug-delivery systems can be developed
      to achieve minimal intervention fertility control without influencing normal
      ovarian function and/or causing adverse hormonal effects. With hormone
      replacement therapy in postmenopausal women, research suggests that progestogens
      delivered directly to the uterine mucosa could reduce side effects and minimize
      reversal of the beneficial effect of estrogens. Various "frameless" and "framed"
      intrauterine systems are currently being clinically evaluated. They are less
      troublesome than the available intrauterine systems and could therefore be
      suitable for use in the majority of women for contraception and treatment
      purposes (e.g., menorrhagia, hormone replacement). These systems require a single
      short office procedure, and have a low morbidity, which is undeniably linked with
      more invasive methods and systemic hormonal contraceptives. Due to the
      technological progress miniature, low-dose, long-term intrauterine drug-delivery
      systems offer enhanced effectiveness, reduced side effects, and optimal user
      compliance. Although there is minimal absorption in the systemic circulation,
      they deserve the status of a locally acting method that should be regarded as
      fundamentally advantageous, if effective, to systemically applied medications
      that may have potentially inherent ill side effects.

PMID- 14644825
TI  - The levonorgestrel intrauterine system: a clinical perspective from the UK.
AB  - The main contraceptive effects of this valuable product [the levonorgestrel
      intrauterine system (LNG-IUS)] are by endometrial suppression and changes to the
      cervical mucus and uterotubal fluid that impair sperm migration. The blood levels
      of LNG are very low, so progestogenic symptoms are uncommon. Most women still
      ovulate and in the remainder sufficient estrogen for health is produced from the
      ovary, even if they become amenorrhoeic, as many do; this is primarily a local
      end-organ effect and should be seen as a benefit. Although usable by selected
      nulliparae, it is ideal for the parous woman. It has unsurpassed efficacy, and
      return of fertility is rapid. Combining the best features of hormonal and
      intrauterine contraception, its gynecological benefits are impressive: the LNG
      IUS user can expect a dramatic reduction in the amount and, after the first few
      occasionally troublesome months, in the duration of blood loss. Hemoglobin levels
      rise and dysmenorrhea is usually greatly benefited, unlike with current uterine
      ablation techniques. In perimenopausal women, it can protect the endometrium from
      overstimulation when estrogen replacement therapy (ERT) is added, by any chosen
      route. It thus provides a contraceptive modality of ERT with, usually, no
      bleeding and few progestogenic side effects-and is applicable before final
      ovarian failure. In summary, adverse side effects are few and in general they are
      not in the "hazardous" category. Regarding the admitted inconvenience of the
      first weeks of light postinsertion bleeding and the early phase low incidence of
      steroidal side effects: good counseling is paramount, since forewarned is
      forearmed!

PMID- 14644826
TI  - Oral contraception over the age of 40.
AB  - Scientific data from the past decade have proved that the age of 35 years is not
      an obligatory border at which to stop taking oral contraceptives (OCs). Combined
      OC formulations (COCs) are safe and effective for healthy women up to the age of
      the menopause. The use of OCs in women who do not smoke does not result in an
      increased risk of cardiovascular disease. Since the risk of thromboembolism
      increases with age and the level of obesity in women of 40 and over, it is wise
      to prescribe the lowest available dose of ethinyl-estradiol in the COCs. Some
      authors prefer levonorgestrel to any third-generation progestogen in COCs, but
      the excess risk of venous thromboembolism associated with the use of third
      generation products can be balanced by the reduced risk of myocardial infarction
      associated with the same products. When OCs are considered for perimenopausal
      women, it is important to take into account progestogen-only pills. In
      consequence of the reduced fecundity, these have a better contraceptive efficacy
      in this age group than in women aged below 35 years. Their only important
      possible adverse effect is an unpredictable bleeding pattern; further, they do
      not alleviate climacteric symptoms if these are present. In such cases,
      progestogen-only pills can be combined with cyclic hormone replacement therapy.

PMID- 14644827
TI  - Oral contraceptives and reproductive system cancer.
AB  - Extensive research during the last 20 years has shown that oral contraceptives
      are safe. Several recent epidemiological studies have confirmed that combined
      oral contraceptives (COCs) provide substantial protection against endometrial and
      ovarian cancer, and this protection is long-lasting and may persist for 15 or
      more years after termination of OC use. In many studies COCs have been associated
      with an increased risk of cervical abnormalities and cervical cancer, but there
      might be alternative explanations for these epidemiological associations (COC
      users can start having sexual intercourse at an earlier age, they have more
      sexual partners, and they rarely use barrier methods of contraception), so OCs
      act as a promoter for HPV-induced carcinogenesis. Finally, women who are
      currently using COCs or have used them in the past 10 years are at a slightly
      increased risk of having breast cancer during the next 10 years, although the
      additional cancers diagnosed tend to be localized to the breast and they are less
      advanced clinically than the cancers diagnosed in those who have never used COCs.

PMID- 14644828
TI  - Steroid receptors in the uterus: implications in endometriosis.
AB  - Receptor proteins for estrogens, progesterone, androgens, and glucocorticoids
      have been detected in the various cell types of the uterus. Reference is made to
      the genes encoding these receptors, to the structure of the receptor proteins,
      and their functional domains. The mode of action of steroid hormones by gene
      activation, through their cognate receptors, and by nongenomic effects is briefly
      presented. The role of the steroid receptors in uterine physiology and the
      significance of the use of steroid receptor knock-out animals in delineating the
      in vivo action of the hormones is discussed. Recent results on the possible
      correlation of steroid receptor gene polymorphisms and of quantitative and
      qualitative changes in the receptor proteins to the etiopathology of
      endometriosis are reviewed.

PMID- 14644829
TI  - Urokinase-type plasminogen activator and insulin-like growth factor-binding
      protein 3 mRNA expression in endometriotic lesions and eutopic endometrium:
      implications for the pathophysiology of endometriosis.
AB  - The peritoneal fluid of women with endometriosis contains an increased insulin
      like growth factor 1 (IGF-1) bioavailability, which is produced by limited
      hydrolysis of urokinase-type plasminogen activator (uPA) on IGF-binding protein 3
      (IGFBP-3). Recently, IGF-1 was shown to inhibit apoptosis of endometrial-like
      cells in vitro, suggesting that a microenvironment of increased IGF-1
      bioavailability can optimize the survival of endometrial cells grown ectopically.
      Here the expression of mRNA of IGFBP-3 and uPA in tissue biopsies from eutopic
      endometrium and endometriotic lesions obtained at laparoscopy from women with
      endometriosis have been analyzed, and it is documented that both IGFBP-3 and uPA
      mRNA expression are increased from 3- to 10-fold in endometriotic lesions versus
      eutopic endometrium. Consequently, the necessary components (uPA and IGFBP-3
      expression) of endocrine/autocrine/paracrine enhancement of local IGF
      bioavailability mediated by uPA hydrolysis of the IGFBP-3 were present in
      endometriotic lesions. These data possibly explain the origin of the increased
      content of uPA activity, IGF-1 bioavailability, and NH(2)-truncated forms of
      IGFBP-3 in the peritoneal fluid of women with endometriosis.

PMID- 14644830
TI  - Endometriosis: treatment strategies.
AB  - Endometriosis is often a perplexing medical condition for both the physician and
      the patient. Accordingly, development of treatment strategies based on the needs
      of the individual patient is highly desirable. Although endometriosis has been
      part of the clinical practice for almost a century, many questions remain
      relating to the relationship between endometriosis and infertility as well as
      endometriosis and pelvic pain. Endometriosis is a disease of reproductive-age
      women, and it is now well recognized that a genetic susceptibility appears
      probable. The prevalence in the general population has never been clearly
      established. Factors to consider in management include the age and reproductive
      desires of the patient, the stage of the disease, and, most importantly, the
      symptoms. Therapeutic options include no treatment, medical therapy, surgery, or
      combination therapy. Oral contraceptives, androgenic agents, progestins, and
      gonadotropin releasing hormone (GnRH) analogs have all been used successfully,
      although at the present time, the latter preparations are the most popular
      medical therapy for endometriosis. Leuprolide acetate, goserelin acetate, and
      nafarelin acetate are all effective agents. Surgical therapy is appropriate,
      especially for advanced stages of the disease. Laparoscopy is an effective
      surgical approach with the goal of excision of visible endometriosis in a
      hemostatic fashion. Since endometriosis is a chronic condition, it is not
      uncommon for recurrences to occur. While endometriosis remains an enigmatic
      disease, the introduction of new pharmacologic agents, such as GnRH analogs and
      newer endoscopic methods of surgical treatment, have facilitated and improved the
      overall management of this disease.

PMID- 14644831
TI  - Evaluation of the role of laser treatment for the treatment of pain in
      endometriosis.
AB  - There have been few appropriately conducted trials to evaluate the effectiveness
      of laser destruction of endometriosis in relieving pain symptoms, yet the
      techniques are increasingly being used. Laser destruction has been shown to be
      more effective than the placebo effect of laparoscopy alone in one trial, at
      least at 6-month follow-up. Longer-term studies suggest increasing recurrence of
      symptoms with time [23% at 12 months in one study, and 44% by a mean of 19.7
      months (5-60) follow-up]. These recurrence rates are similar to those seen
      following 6 months medical treatment. It is unknown whether laparoscopic
      uterosacral nerve ablation (LUNA) in addition to destruction of lesions will
      produce better results, and appropriate trials are needed in several areas to
      determine the role of laser therapy.

PMID- 14644832
TI  - Endometriosis and reproductive disorders.
AB  - The classic concept of endometriosis as a cause of infertility is challenged.
      Traditionally, both surgical and medical therapy have focused on alleviation of
      symptoms, prevention of disease progression, and promotion of fertility. In spite
      of significant developments in medical and surgical approaches, the optimal
      therapy for treating endometriosis-associated infertility has yet to be
      established. The relationship between prevalence of fecundity and stage of the
      disease was studied according to the type of management. Of 151 women who were
      consecutively proved by laparoscopy to have endometriosis stage I and II,
      operative laparoscopy was performed in 49, medical treatment in 59, and expectant
      management in 43 cases. During a 24-month period, the cumulative pregnancy rates
      were 36.7%, 30.5%, and 20.9%, respectively. Survival analysis over the 20 weeks
      of pregnancy showed that the probability of carrying the pregnancy beyond this
      week was 30.6%, 25.4%, and 16.2%, respectively. Of 64 patients with advanced
      disease, 34 (53%) became pregnant during the 2-year follow-up period. A
      significantly increased pregnancy rate was found for the first year as compared
      to the second (76% vs. 24%). The existence of adhesions affected adversely the
      outcome of the treatment when early achievement of pregnancy is considered.
      Diagnosis and treatment of endometriosis was beneficial for the infertile women.
      Laparoscopic surgery seems to be the best treatment in these cases, as it
      increases the fecundity and involves minimal risk.

PMID- 14644833
TI  - Pelvic adhesions: laparoscopic approach.
AB  - A retrospective study using the American Fertility Society's Adhesion Scoring
      Method and the MCASM (More Comprehensive Adhesion Scoring Method) and a
      prospective, randomized, controlled, multicenter trial (Canadian Task Force
      Classification I) were conducted. Of 2124 cases operated by laparoscopy, 465
      patients had adhesions. Fifty-one female patients underwent open or laparoscopic
      myomectomy procedures with vs. without application of SprayGel adhesion barrier
      prevention, followed by second-look laparoscopy to evaluate postoperative
      adhesions. Details of the 465 cases of adhesiolysis are given. In subgroup 1 (n =
      34) there were no preexisting adhesions. All 34 patients were assessed at a
      second-look laparoscopy for adhesion occurrence after 6-8 weeks; 29.4% were found
      to have no adhesions and 70.6% of patients had significant or mild adhesions. In
      subgroup 2, 21 patients who had undergone previous surgery for adhesiolysis were
      operated upon again, and 24% revealed an increased adhesion score, 57% the same
      adhesion score, and 19% a reduced adhesion score at second-look laparoscopy. Out
      of 51 patients enrolled, 45 were randomized to either treatment (n = 24) or
      control (n = 21). Three to sixteen weeks following surgery, 18 of 24 treatment
      patients (75%) and 13 of 21 controls (61.9%) had second-look laparoscopies (SLL).
      SLL showed 5 of 18 treatment patients (27.8%) were adhesion free vs. 1 in 13 of
      controls (7.7%). Patients randomized to SprayGel treatment were 3.6 times more
      likely to be adhesion free than patients randomized to control. Compared to the
      initial surgery, the severity score showed a 22% reduction in the treated group
      vs. a 39% increase in the control group, and a 12% reduction of adhesion area in
      the treated group vs. a 37% increase in the control group at SLL. New data
      confirmed previous knowledge: To avoid adhesions you must avoid surgery. If
      surgery has to be performed, laparoscopic surgery causes fewer adhesions than
      laparotomy. SprayGel was shown to be effective in reducing postoperative
      adhesions after laparoscopic and open myomectomy. Application of this adhesion
      barrier prevention system is fast, easy, and safe. Further studies are needed to
      confirm the promising results of this interim analysis.

PMID- 14644834
TI  - Laparoscopic management of patients with endometriosis and chronic pelvic pain.
AB  - Endometriosis has been traditionally included among the most important causes of
      chronic pelvic pain (CPP) in women of reproductive age. The main clinical
      manifestations of endometriosis are dysmenorrhea, dyspareunia, and chronic
      nonmenstrual pain. Despite the high prevalence of endometriosis in women
      suffering from CPP, controversy still exists regarding the true association
      between the stage and extent of this peculiar disease and the severity of pain.
      Over the last decade, advances in endoscopic technology have enabled gynecologic
      surgeons to recognize many atypical appearances of the endometriotic implants not
      known to exist before, thus allowing their complete excision or destruction.
      Laparoscopic surgery may offer considerable relief in patients with endometriosis
      and CPP. Although cases with advanced endometriosis seem to benefit the most, we
      also support surgical treatment in patients with early endometriosis diagnosed
      using laparoscopy, as many will experience improvement in their symptoms.

PMID- 14644835
TI  - Laparoscopic management of peritoneal endometriosis, endometriotic cysts, and
      rectovaginal adenomyosis.
AB  - Peritoneal endometriosis is probably caused by the implantation of regurgitated
      menstrual cells. The ovarian endometrioma is the consequence of non-hormone
      regulated bleeding from intraovarian epithelial inclusions after they have
      undergone metaplasia into endometrial-like tissue. Rectovaginal adenomyosis is,
      in fact, an adenomyotic lesion and can develop from Mullerian rests. In
      conclusion, peritoneal endometriosis, ovarian endometriosis, and rectovaginal
      adenomyotic nodules must be considered as three separate entities with different
      pathogeneses that require a different therapeutic approach.

PMID- 14644836
TI  - Laparoscopy and oncology: where do we stand today?
AB  - The clinical application of laparoscopic surgery has grown rapidly over the last
      few years. Since the first documentations of laparoscopic lymphadenectomy, many
      reports highlight the use of modern laparoscopy in the field of gynecologic
      oncology. Laparoscopic treatment of early-stage cervical and endometrial cancer,
      and laparoscopic evaluation and staging of cervical, ovarian, and endometrial
      carcinomas, are feasible procedures. The place of minimal-access surgery in the
      arsenal of gynecologic oncological surgery has been established, especially after
      the recent developments and practical application of video laparoscopy, novel
      instrumentation, and advanced surgical techniques. Although operative laparoscopy
      in gynecologic oncology is still in its infancy the potentiality of the procedure
      is underscored. Many patients may benefit from the treatment or staging of
      gynecologic malignancies with laparoscopic means. Literature reports highlight
      that laparoscopy may be an effective procedure with lower morbidity and
      complication rates than traditional abdominal surgery. The short hospital stay
      and recovery time have a positive impact in a cancer patient's quality of life,
      as they return to normal activities rapidly. Many risks, though, may arise from
      the application of minimal-access surgery in cancer patients, and many questions
      regarding safety and efficacy need answers, based on prospective clinical trials.
      We must emphasize that such studies with large patient numbers and long-term
      follow-up are lacking. Until results from these trials are available,
      laparoscopic oncologic procedures should be performed only in an investigational
      setting by expert teams.

PMID- 14644837
TI  - Androgens and antiandrogens.
AB  - The role of androgens in women's health has been generally neglected. Currently
      available assays are lacking in sensitivity and reliability at the lower ranges.
      Circulating androgens as prohormones for other steroids (e.g., androgens) have an
      ubiquitous role on diverse physiological and behavioral systems. Clinical
      assessment of both androgen production and androgen availability can be achieved
      by measurement of two or three essential values. These include either total T and
      sex-hormone binding globulin (SHBG), free T and SHBG, or free T and total T. The
      free testosterone index (total T/SHBG) correlates well with free or bioavailable
      T and can be used as a substitute. DHEA-S is the most useful measure of adrenal
      androgen production in women. Androgen insufficiency in women is not a specific
      consequence of natural menopause, but may occur secondarily to the age-related
      decline in both adrenal and ovarian androgen production. Since estrogen effects
      are also strongly linked to mood, psychological well-being, and sexual function
      in women, the diagnosis of androgen insufficiency should only be made in women
      who are adequately estrogenized. Before initiating a trial of androgen
      replacement therapy, a comprehensive clinical assessment should be performed in
      all cases. Approved androgen replacement therapy is not yet available in most
      countries for treatment of female sexual dysfunction. This would include T
      supplements or DHEA. Several new progestins have been synthesized in the last
      decade. Dienogest is a hybrid progestin that is derived from both the pregnane
      and the estrane groups with a 17alpha-cyanomethyl radical; drospirenone is
      derived from spirolactone. Somehow, the molecules available have demonstrated
      antiandrogenic properties. Cyproterone acetate (CPA) is the most potent
      antiandrogenic progestin, followed by dienogest, drosperinone, and chlormadinone
      acetate. Nomegestrol acetate and medrogestone also exert some antiandrogenic
      properties and are similar to chlormadinone acetate in antiandrogenic potency.
      While androgens act positively on libido in women, antiandrogenic properties in
      doses used in HRT do not appear to have a negative effect. Progestins used in HRT
      have varying pharmacological properties that are associated with different
      adverse effects. The new progestins with antiandrogenic properties avoid many of
      the androgenic side effects related to testosterone-derived progestins. They also
      have the potential of not counteracting beneficial estrogen effects, for example,
      on the cardiovascular system or mental tone.

PMID- 14644838
TI  - The management of polycystic ovary syndrome.
AB  - It is well known that subjects with polycystic ovary syndrome (PCOS) show very
      variable clinical and biochemical aspects. Considering long-term repercussions,
      two main disturbances, not always strictly related, need to be countered:
      hyperandrogenism and insulin resistance, with compensatory hyperinsulinemia. The
      aim of this review is to summarize therapeutic perspectives for PCOS, starting
      from basic approach, such as weight reduction and changes in lifestyle. The
      benefits of long-term use of oral contraceptives and the criteria of choice of
      the estro-progestin combinations are discussed. With severe hyperandrogenism, a
      pure antiandrogen should be added. The experiences with insulin-sensitizing
      drugs, especially metformin, are reviewed; while their beneficial role as an
      adjuvant to treatment of ovulatory infertility has been well established, the
      effects of a long-term treatment, especially in very young patients, are still
      under debate. Current studies are testing the results of combinations of
      different treatments at low dosage; randomized comparative trials on the long
      term efficacy of these approaches have yet to be scheduled.

PMID- 14644839
TI  - Conservative management of gynecologic diseases: insulin sensitizing agents in
      polycystic ovary syndrome.
AB  - A contemporary "Pandora's box" could be the polycystic ovary syndrome (PCOS),
      containing several negative features for a woman: compromised looks, compromised
      fertility; increased metabolic risk factors; and compromised general health.
      During the past decade, the central importance of insulin resistance (IR) in the
      pathogenesis of this syndrome has been established. Several in vivo and in vitro
      studies have demonstrated this phenomenon, initially by the hyperinsulinemic
      response to oral glucose in obese and lean women with PCOS compared with weight
      matched normal women, and subsequently with more sensitive techniques like
      euglycemic hyperinsulinemic clamp. In vitro studies have corroborated these
      findings, showing molecular defects at the postreceptor level of insulin action,
      such as increased serine phosphorylation and decreased phosphoinositol 3-kinase
      action. Insulin sensitizers are the group of therapeutic agents that hold some
      promise of helping women with polycystic ovary syndrome (PCOS), since the role of
      insulin resistance and hyperinsulinemia appear to be major contributors to the
      pathophysiology of the syndrome. The therapeutic approach with insulin
      sensitizers appears to have beneficial effects on the metabolic as well as on the
      reproductive abnormalities in women affected by PCOS. Finally, insulin
      sensitizers should be considered by all subspecialists who aim at a comprehensive
      management of patients with PCOS.

PMID- 14644840
TI  - Premenstrual syndrome and the use of alternative therapies.
AB  - Premenstrual syndrome is a collection of symptoms that may be encountered by up
      to 95% of the population, although it is estimated to affect 5% of women
      severely. The use of complementary and alternative therapies is high among this
      group, but does not seem to compromise conventional treatment. It has been
      established that complementary therapies are used by a large proportion of the
      developed world, but their efficacy and safety are not always proven. This is
      partly due to the difficulty of studying alternative practices and the cost, but
      also with respect to premenstrual syndrome, problems with defining the condition
      and specifying end points are encountered. The difficulties in evaluating
      unorthodox therapies are elucidated and the evidence base for nonprescribed
      treatments for premenstrual syndrome is presented. Overall these women are a
      neglected group for whom the evidence for conventional therapy is sparse and
      controversial. Since the majority of women self-diagnose and self-medicate, it is
      important that physicians have an understanding of the variety of interventions
      tried and their worth.

PMID- 14644841
TI  - Breast cancer and hormonal replacement therapy.
AB  - Understanding the association between hormone replacement therapy (HRT), the
      diagnosis of breast cancer, and the clinical outcome of women who develop breast
      cancer in the setting of HRT continue to present important challenges for health
      professionals and the public. The general impression in the medical community is
      that breast cancer is diagnosed more frequently after prolonged HRT; however,
      whether a causative relationship exists between HRT and breast cancer remains
      uncertain. Despite the increase in breast cancer diagnosis, clinical outcome of
      the disease appears favorable for women who develop breast cancer after HRT; HRT
      users tend to present with more localized tumors that exhibit favorable
      histology, and overall death from breast cancer appears reduced. The history of
      breast cancer constitutes a contraindication for HRT as a general rule, based on
      the concern that HRT may activate dormant cancer cells. Direct evidence for this
      practice is very limited; available studies are small and mostly retrospective,
      but do not indicate an adverse effect of HRT on breast cancer recurrence. In
      reaching a clinical decision regarding HRT, the expected benefits (largely
      improvement of menopausal symptoms) must be weighed against the potential risks
      of HRT (especially breast cancer) for each individual woman.

PMID- 14644842
TI  - Hormone replacement therapy and cardioprotection: the end of the tale?
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in
      women after the age of 50 years in most developed countries. Estrogen deficiency
      plays a key role in causing CVD in women. Apart from the direct effect of ovarian
      hormones on the vessel wall, cessation of ovarian function and the consequent
      reduction of sex steroid hormone levels have important metabolic and pathological
      implications that negatively influence the cardiovascular system. Therefore, the
      increased incidence of CVD observed in women after menopause should be considered
      on a multifactorial basis. Data available for the effects of ERT and HRT in the
      primary prevention of CVD are mainly observational. However, despite limitations
      related to this kind of study, it must be noted that their results consistently
      show a reduction in cardiovascular events in hormone users. Meta-analysis of
      epidemiological studies found that women who had ever used estrogens had a 34%
      overall reduction in the relative risk of cardiovascular events compared to those
      who had never used hormones. Most of the early epidemiological studies were
      conducted using unopposed estrogen replacement therapy. The number of studies
      evaluating the effects of estrogen-progestin replacement therapy is limited.
      Recently, the estrogen-progestin arm of the Women's Health Initiative (WHI) study
      has been stopped because of an increased incidence of breast cancer, and too
      early on to give any insight into possible cardiovascular effects. Comments on
      the cardiovascular effects of HRT from the results of the WHI study are therefore
      not warranted, as the study did not continue for a duration long enough to enable
      a calculation of cardiovascular end points. The WHI study included only one
      single type of estrogen-progestin association; whether different estrogen
      progestin combinations, more commonly used outside the United States, may have a
      different effect is still a matter of speculation. A major difference between
      observational and randomized studies on the effect of ovarian hormones on
      cardiovascular function is the time of HRT initiation since menopause, which is
      significantly shorter in observational studies. In conclusion, the average 35-50%
      risk reduction in CVD with HRT in primary prevention in postmenopausal women is
      based on nonrandomized observational data.

PMID- 14644843
TI  - HRT and cardiovascular disease.
AB  - Recent randomized controlled clinical trials failed to confirm a perceived
      beneficial effect on cardiovascular disease by hormone therapy. Given the huge
      amount of observational data, as well as experimental data both in humans and
      various animal species, there is reason to believe that female sex steroids, in
      particular estrogen, possess cardiovascular benefits. The type, dose, and mode of
      administration of exogenous sex steroids may modify and even negate the
      beneficial effects. The results of the randomized trials, especially the WHI,
      should encourage the scientific community to try to define a target population in
      which benefits outweigh harm, as it must be regarded as proven that any hormone
      therapy regimen given to any population will not reach that goal. The recent
      finding that transdermal estrogens, in contrast to oral preparations, do not seem
      to be associated with an increased risk of venous thrombosis is challenging. It
      would seem appropriate to conclude that estrogens prevent arteriosclerosis. On a
      long-term basis, however, other more rapid effects on the cardiovascular system
      could be negative. Such an assumption contributes to the explanation of the
      discordant results from cohort studies versus randomized trials. Admittedly the
      current picture is complex, but far from definitive, and should challenge us all
      to continue research in this area.

PMID- 14644844
TI  - The role of selective estrogen receptor modulators (SERMs) in postmenopausal
      health.
AB  - Concerns about long-term therapy with HRT have recently highlighted interest in a
      class of compounds active in the estrogen receptor, but with selectivity in their
      actions, known as the selective estrogen receptor modulators (SERMs). Tamoxifen
      is recognized as the first widely marketed SERM, but its selectivity focuses
      interest on its approved indications: the treatment and prevention of breast
      cancer. Raloxifene has been approved in most countries of the world for the
      treatment and prevention of osteoporosis, and it displays a pattern of actions
      highly matched to the needs and concerns of many postmenopausal women. Further
      study of current and future SERMs promises to open new vistas in patient-specific
      management of the field of postmenopausal health.

PMID- 14644845
TI  - CNS: sex steroids and SERMs.
AB  - The central nervous system (CNS) is one of the main target tissues for sex
      steroid hormones, which act both through genomic mechanisms, modulating
      synthesis, release, and metabolism of many neuropeptides and neurotransmitters,
      and through nongenomic mechanisms, influencing electrical excitability, synaptic
      function, and morphological features. The identification of the brain as a de
      novo source of neurosteroids modulating cerebral function, suggests that the
      modifications in mood and cognitive performances occurring in postmenopausal
      women could also be related to a modification in the levels of neurosteroids,
      particularly allopregnanolone and DHEA, GABA-A agonist, and antagonist,
      respectively. The selective estrogen receptor modulators (SERMs) are compounds
      that activate the estrogen receptors with different estrogenic and antiestrogenic
      tissue-specific effects. In addition to the effects of the classic steroid
      hormones on the CNS, the study of selective estrogen receptor modulators impact
      on the neuroendocrine system has recently provided encouraging results,
      indicating that raloxifene analog LY 117018 and the new generation SERM EM-652
      have an estrogen-like action on beta-endorphin and on allopregnanolone in
      ovariectomized rats, while they exert an anti-estrogenic effect in fertile rats
      and in ovariectomized rats treated with estrogens. In addition, raloxifene
      administration in postmenopausal women plays an estrogen-like effect on
      circulating beta-EP and allopregnanolone levels, and it restores the response of
      beta-EP and allopregnanolone to neuroendocrine tests. In conclusion, the positive
      effects of HRT on mood and cognition in postmenopausal women occur via the
      modulation of neuroendocrine pathways and probably also of neurosteroidogenesis.
      The effects of raloxifene on mood and cognition encourage the efforts in the
      research of an ideal estrogen replacement therapy, showing all the positive
      effects of estrogens and fewer side effects.

PMID- 14644846
TI  - Seronegative antiphospholipid syndrome.

PMID- 14644847
TI  - Cytokines in the seronegative spondyloarthropathies and their modification by TNF
      blockade: a brief report and literature review.
AB  - Rheumatoid arthritis (RA) is a disease well characterised by proinflammatory
      cytokine secretion (particularly tumour necrosis factor, interferon gamma,
      interleukin (IL) 1, and IL6). Less has been reported about the cytokine profiling
      in the spondyloarthropathies (SpA). Several trials suggest that, similar to RA,
      proinflammatory cytokines are globally expressed in the SpA. However, other
      studies report a down regulation of these cytokines in the SpA, with a relative
      anti-inflammatory polarisation (featuring increases in IL4, IL5, and IL10). This
      review summarises current published reports and the variation in cytokine data in
      the SpA. Additionally, results of cytokine profiles in patients with ankylosing
      spondylitis before and after treatment with etanercept are reported.

PMID- 14644848
TI  - An unusual cause of acute renal failure in systemic sclerosis.
AB  - BACKGROUND: Scleroderma renal crisis is one of the most life threatening
      complications of scleroderma. Enteric hyperoxaluria complicates extensive disease
      or resection of the small intestine in the presence of an intact colon, and is
      associated with calcium oxalate nephrolithiasis. This cause of renal failure may
      be underestimated and should be considered in all patients with malabsorption and
      renal failure. CASE REPORT: A 78 year old woman with systemic sclerosis affecting
      the bowel developed acute renal failure caused by oxalate nephropathy. RESULTS:
      The patient's renal failure improved on an oxalate free diet.

PMID- 14644849
TI  - A fibrin based model for rheumatoid synovitis.
AB  - Intracavitary fibrin clots may initiate pannus formation and the immunopathology
      of RA. Two critical steps, probably host dependent, may determine the development
      of RA: an altered regulation of extravascular haemostasis or an aberrant
      reactivity of synovial fibroblasts to the adhered fibrin clots. Current
      treatments for RA target events downstream of fibrin deposition, perhaps agents
      acting at an earlier stage should be tried.

PMID- 14644850
TI  - p53 in rheumatoid arthritis synovial fibroblasts at sites of invasion.
AB  - OBJECTIVE: To analyse the functional response of p53 in rheumatoid arthritis
      synovial fibroblasts (RASF) in vitro and in vivo and to investigate whether
      activation of p53 modulates the destructive process of RASF. METHODS: RASF and
      controls grown on chamber slides were either directly examined with DO7 anti-p53
      antibodies by immunofluorescence or irradiated with 10 Gy x rays and analysed
      time dependently for the expression of p53. The percentage of positive cells was
      evaluated by a quantitative scoring system. RASF and normal (N) SF cultured in
      vitro were co-implanted with human cartilage in SCID mice for 60 days.
      Consecutively, the invasion score was evaluated, and the number of p53 positive
      cells was determined at the sites of invasion by immunohistochemistry. In
      addition, synovial tissues from RA, osteoarthritis, and normal synovia were
      stained with DO7 antibodies. RESULTS: In vitro the rate of expression of p53 in
      RASF was low (<5%), but transiently inducible by ionising irradiation (50%). In
      vitro low p53 expressing RASF disclosed, when invading articular cartilage, a
      nuclear p53 signal in 20% of the cells, indicating the induction of p53 in a
      distinct population of RASF during the invasive process. CONCLUSIONS: These data
      suggest an inductive p53 response at sites of cartilage invasion during the
      destructive process driven by activated RASF.

PMID- 14644851
TI  - EULAR Recommendations 2003: an evidence based approach to the management of knee
      osteoarthritis: Report of a Task Force of the Standing Committee for
      International Clinical Studies Including Therapeutic Trials (ESCISIT).
AB  - OBJECTIVES: To update the EULAR recommendations for management of knee
      osteoarthritis (OA) by an evidence based medicine and expert opinion approach.
      METHODS: The literature search and guidelines were restricted to treatments for
      knee OA pertaining to clinical and/or radiological OA of any compartment of the
      knee. Papers for combined treatment of knee and other types of OA were excluded.
      Medline and Embase were searched using a combination of subject headings and key
      words. Searches for those treatments previously investigated were conducted for
      January 1999 to February 2002 and for those treatments not previously
      investigated for 1966 to February 2002. The level of evidence found for each
      treatment was documented. Quality scores were determined for each paper, an
      effect size comparing the treatment with placebo was calculated, where possible,
      and a toxicity profile was determined for each treatment modality. RESULTS: 497
      new publications were identified by the search. Of these, 103 were intervention
      trials and included in the overall analysis, and 33 treatment modalities were
      identified. Previously identified publications which were not exclusively knee OA
      in the initial analysis were rejected. In total, 545 publications were included.
      Based on the results of the literature search and expert opinion, 10
      recommendations for the treatment of knee OA were devised using a five stage
      Delphi technique. Based on expert opinion, a further set of 10 items was
      identified by a five stage Delphi technique as important for future research.
      CONCLUSION: The updated recommendations support some of the previous propositions
      published in 2000 but also include modified statements and new propositions.
      Although a large number of treatment options for knee OA exist, the evidence
      based format of the EULAR Recommendations continues to identify key clinical
      questions that currently are unanswered.

PMID- 14644852
TI  - Switching from NSAIDs to paracetamol: a series of n of 1 trials for individual
      patients with osteoarthritis.
AB  - OBJECTIVES: To investigate for individual patients who have been using NSAIDs
      regularly, whether paracetamol is as effective as non-steroidal anti-inflammatory
      drugs (NSAIDs) in the treatment of pain and disability related to osteoarthritis
      of the hip or knee. METHODS: A series of n of 1 trials were conducted in general
      practices in Amsterdam and the surrounding area. Each patient was his or her own
      control and received five pairs of treatments comprising two weeks of an NSAID
      and two weeks of paracetamol. For each pair, the order of treatments was
      randomised. Outcome measures were severity of individual main complaints,
      intensity of pain, satisfaction with drugs, function test, and side effects.
      RESULTS: Thirteen patients were selected. Six patients did not complete the
      study. For five patients completing the study little or no difference was found
      between NSAIDs and paracetamol, for one patient the results favoured the NSAID,
      and for one patient there was no association between outcome and type of drug. It
      was recommended that six patients changed to paracetamol; the others continued
      with NSAIDs. Three months after the end of the study, four of the six patients
      for whom paracetamol had been recommended were taking NSAIDs for practical
      reasons or perceived lack of efficacy. CONCLUSION: The results of the n of 1
      trials varied across patients. n of 1 trials can be used to investigate which
      treatment is best for any specific person, thus avoiding unnecessary prolonged
      treatment with NSAIDs. However, practical reasons may cause patients to switch
      from NSAIDs to paracetamol or not.

PMID- 14644853
TI  - Does hydrotherapy improve strength and physical function in patients with
      osteoarthritis--a randomised controlled trial comparing a gym based and a
      hydrotherapy based strengthening programme.
AB  - OBJECTIVE: To compare the effects of a hydrotherapy resistance exercise programme
      with a gym based resistance exercise programme on strength and function in the
      treatment of osteoarthritis (OA). DESIGN: Single blind, three arm, randomised
      controlled trial. SUBJECTS: 105 community living participants aged 50 years and
      over with clinical OA of the hip or knee. METHODS: Participants were randomised
      into one of three groups: hydrotherapy (n = 35), gym (n = 35), or control (n =
      35). The two exercising groups had three exercise sessions a week for six weeks.
      At six weeks an independent physiotherapist unaware of the treatment allocation
      performed all outcome assessments (muscle strength dynamometry, six minute walk
      test, WOMAC OA Index, total drugs, SF-12 quality of life, Adelaide Activities
      Profile, and the Arthritis Self-Efficacy Scale). RESULTS: In the gym group both
      left and right quadriceps significantly increased in strength compared with the
      control group, and right quadriceps strength was also significantly better than
      in the hydrotherapy group. The hydrotherapy group increased left quadriceps
      strength only at follow up, and this was significantly different from the control
      group. The hydrotherapy group was significantly different from the control group
      for distance walked and the physical component of the SF-12. The gym group was
      significantly different from the control group for walk speed and self efficacy
      satisfaction. Compliance rates were similar for both exercise groups, with 84% of
      hydrotherapy and 75% of gym sessions attended. There were no differences in drug
      use between groups over the study period. CONCLUSION: Functional gains were
      achieved with both exercise programmes compared with the control group.

PMID- 14644854
TI  - Efficacy and safety of the fully human anti-tumour necrosis factor alpha
      monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with
      rheumatoid arthritis: a 12 week, phase II study.
AB  - OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of
      adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory
      patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a
      12 week, double blind, placebo controlled study, 284 patients were randomly
      allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72),
      40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs.
      RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all
      efficacy measures. ACR20 responses with adalimumab were significant at each
      assessment versus placebo (p</=0.01). Additionally, ACR responses with adalimumab
      were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate
      ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for
      adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%,
      respectively, versus 10.0% for placebo (p</=0.001 for all comparisons); ACR50
      rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo
      (p</=0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%,
      respectively, versus 0.0% for placebo (p</=0.05 for all comparisons). All
      adalimumab doses significantly improved all ACR core criteria at all assessments.
      The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was
      generally well tolerated, with only mild or moderate adverse events. Completion
      rates were 87% for adalimumab and 67% for placebo. CONCLUSIONS: Adalimumab given
      as monotreatment to patients with longstanding, severe RA refractory to
      traditional DMARDs produced a rapid, sustained response and was safe and well
      tolerated, with no dose limiting side effects.

PMID- 14644855
TI  - Quality of life and work in patients with rheumatoid arthritis and ankylosing
      spondylitis of working age.
AB  - OBJECTIVE: To investigate the relationship between work and quality of life (QOL)
      in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) aged
      16-59. METHODS: 1056 patients with RA and 658 with AS were included in the study.
      Data were obtained by postal questionnaire, which included several generic and
      disease related QOL instruments. Separate dimensions and physical and mental
      summary scores from the SF-36 were compared. Stepwise multiple regression was
      performed to study the relationship between work and physical and mental health
      related QOL, including disease related factors, coping, and fatigue. RESULTS:
      Physical health related QOL was reported to be worse, and mental health related
      QOL better, in RA than in AS in people of working age. No differences between RA
      and AS were found in somatic pain, physical role functioning, social functioning,
      emotional role functioning, vitality, or general health perception; nor were
      there any significant differences in fatigue and behavioural coping styles. Work
      was positively associated with physical health related QOL in both groups and,
      after disease characteristics, was the most important determinant. No association
      was found with mental health related QOL. CONCLUSIONS: Although physical health
      related QOL was worse in patients with RA, the impact on several dimensions of
      health related QOL in patients with RA and AS of working age under
      rheumatological care was comparable. Patients with RA and AS experienced similar
      limitations in physical role functioning, including work. Work is an important
      independent external determinant of physical health related QOL, but not of
      mental health related QOL.

PMID- 14644856
TI  - Cancer incidence among patients with ankylosing spondylitis in Sweden 1965-95: a
      population based cohort study.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory joint disease
      which may lead to extra-articular complications. The disease associated cancer
      risk has been poorly explored. Recently, tumour necrosis factor alpha blockers
      have been found to be efficacious in AS, but their long term risk is unknown.
      OBJECTIVE: To analyse a large national cohort of patients with AS to determine
      the overall cancer risk in AS as a background to the future introduction of new
      treatments. METHODS: All patients with AS admitted to Swedish hospitals 1965-95
      were linked through individual national registration numbers to the Swedish
      Cancer Register and National Death Register. Standardised incidence ratio (SIR)
      of cancer risk was calculated in 6621 people, monitored during 67 885 person
      years. RESULTS: No overall increase in cancer risk was found (SIR 1.05, 95% CI
      0.94 to 1.17). Rectal cancer was less common (SIR 0.41, 95% CI 0.15 to 0.89)
      while unspecified kidney cancer was more common (SIR 5.90, 95% CI 1.61 to 15.1).
      Risks for colon, renal parenchymal, and renal pelvic cancer were not
      significantly increased. Laryngeal cancer was more common than expected, while
      lung cancer was not. Risks of haematopoietic malignancies were not increased.
      CONCLUSIONS: No overall increase in cancer risk was found. The decreased risk of
      rectal cancer might be due to local application of NSAIDs, and the increased risk
      of unspecified kidney cancer to frequent radiological pelvic examinations. If
      information on disease characteristics, including HLA-B27, was available for
      individual patients with cancer, risk-benefit analysis of long term effects of
      new immunomodulation treatment might be improved.

PMID- 14644858
TI  - Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice
      versa: data from the STURE registry showing that switching tumour necrosis factor
      alpha blockers can make sense.
AB  - OBJECTIVE: When one TNFalpha blocker (etanercept or infliximab) has failed, to
      determine whether it makes sense to treat patients with the other. PATIENTS AND
      METHODS: Since 1999 patients treated with etanercept or infliximab have been
      systematically followed up at our institution in the STURE database. We
      identified 31 patients who had received both agents. RESULTS: Eighteen patients
      received etanercept first; discontinuation was mostly due to lack of efficacy.
      DAS28 values had improved only slightly with etanercept, with a mean (SEM) best
      DAS28 value of 4.8 (0.6). After switching to infliximab, the mean best DAS28 was
      3.6 (0.6)-significantly better than the previous result (p<0.05). Similarly, the
      mean best ACR-N during etanercept treatment was 17.2 (6.65) and during subsequent
      infliximab treatment 40.4 (10.6) (p = 0.08). Thirteen patients received
      infliximab first; discontinuation was mainly due to adverse events. The best
      DAS28 value achieved during etanercept was 3.6 (0.4) compared with 4.1 (0.4) for
      infliximab (p<0.05), but the change in DAS28 was not different and ACR-N were
      similar for infliximab and etanercept in this group. CONCLUSION: For patients
      with insufficient efficacy from etanercept, treatment with infliximab provided
      better results, suggesting that a trial of infliximab is reasonable for such
      patients. For patients who discontinued infliximab owing to adverse events,
      treatment with etanercept gave at least similar clinical efficacy. Taken
      together, these data provide support for a trial of the reciprocal TNFalpha
      blocker in patients when one such agent has failed.

PMID- 14644857
TI  - EULAR response criteria for polymyalgia rheumatica: results of an initiative of
      the European Collaborating Polymyalgia Rheumatica Group (subcommittee of
      ESCISIT).
AB  - OBJECTIVE: To develop response criteria for polymyalgia rheumatica (PMR) for
      monitoring treatment and comparing alternative treatments regimens. METHODS: 76
      patients, mean (SD) age 68.7 (7.7) years, were enrolled. Corticosteroids, and non
      steroidal anti-inflammatory drugs (NSAIDs) were the only drugs allowed during the
      observation period. Erythrocyte sedimentation rate (ESR), C reactive protein
      (CRP), alpha(2) globulin, serum iron, pain, physician's global assessment (PGA),
      morning stiffness (MST), muscle tenderness (MT), myalgia, and the elevation of
      upper limbs (EUL) were determined regularly. The daily corticosteroid and NSAID
      doses as the corticosteroid response time were recorded. To ensure evaluation of
      an adequate number of patients (n = 57) week 24 was chosen for final analysis.
      RESULTS: ESR, CRP, alpha(2) globulin, pain, PGA, MST, myalgia, MT, and EUL showed
      significant improvement (p<0.0001) at week 24 compared with week 0. Multiple
      regression analysis showed that changes of ESR (p = 0.08), CRP (p = 0.41),
      alpha(2) globulin (p = 0.13), MST (p = 0.1), and MT (p = 0.07) were independent
      of pain, but myalgia (p<0.001) and EUL (p = 0.003) were pain dependent.
      Consequently, a core set of PMR response criteria, comprising ESR or CRP, pain,
      PGA, MST, and EUL was established. Assessment of treatment responses with this
      core set resulted in 90%, 70%, 50%, and 20% improvement in 31/57 (54%), 46/57
      (81%), 51/57 (89%), and 54/57 (95%) of the patients, respectively. CONCLUSION:
      These PMR response criteria are a promising tool for better monitoring of disease
      activity and treatment in PMR. It is proposed that these criteria should be used
      in clinical trials in the near future to explore alternative treatment options
      for PMR.

PMID- 14644859
TI  - Prevalence and associations of an abnormal ankle-brachial index in systemic lupus
      erythematosus: a pilot study.
AB  - BACKGROUND: Accelerated atheroma is a well recognised complication of systemic
      lupus erythematosus (SLE). Its aetiology is multifactorial and several methods
      may be used to detect early signs of atheroma. METHODS: Patients aged </=55 years
      were screened using the ankle-brachial index (ABI). Ninety one patients aged
      </=55 years and fulfilling the revised American College of Rheumatology criteria
      for SLE were studied. The ABI was measured using a contour wrapped 12 cm cuff
      attached to a mercury sphygmomanometer and an 8 MHz Doppler probe in the arms and
      legs; a ratio of <1 was considered abnormal. RESULTS: The mean (SD) age of the
      patients was 39.0 (9.2) years. Of the 91 patients studied, 34 (37%) had an
      abnormal ABI. Only one patient was mildly symptomatic. Abnormal ABI correlated
      with age but not with disease duration, cumulative steroid dosage, ECLAM score,
      or any other traditional risk factors for atherosclerosis. In comparison with
      population studies, the prevalence of an ABI<1 in the patients with SLE with a
      mean age of 39 years was similar to that in adults aged over 80. CONCLUSION: In
      this pilot study, patients with SLE with a mean age of 39 years had a high
      prevalence of an abnormal ABI. The ABI is a simple non-invasive tool for the
      early detection of accelerated atheroma in SLE.

PMID- 14644860
TI  - Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren's
      syndrome: a randomised 12 week controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and side effects of oral pilocarpine for the
      treatment of ocular symptoms in patients with primary Sjogren's syndrome (SS).
      METHODS: A 12 week, single centre, randomised controlled study was performed.
      Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg
      twice a day), 28 only artificial tears, and 28 inferior puncta occlusion.
      Patients receiving oral pilocarpine and those with inferior puncta occlusion also
      received artificial tears. Patients were evaluated at baseline and throughout the
      study for their subjective global assessment of dry eyes and for their objective
      assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test).
      RESULTS: Patients taking oral pilocarpine had significant improvement in
      subjective global assessment of dry eyes, as was evaluated by improvement of >55
      mm on a visual analogue scale (VAS) for responses to the eye questionnaire,
      compared with patients treated with artificial tears (p<0.001) and those with
      inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral
      pilocarpine also showed greater objective improvement, as measured by the rose
      bengal test (p<0.05), while Schirmer's-I test showed no differences between the
      treated groups. Commonly reported adverse events were headache, increased
      sweating, nausea, and vomiting in the pilocarpine group, while one patient in the
      inferior puncta occlusion group had blepharitis and was withdrawn from the study.
      CONCLUSION: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had
      a beneficial effect on subjective eye symptoms, as evaluated by improvement >55
      mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but
      an increase in tear production, as measured by the Schirmer-I test, was not
      substantiated.

PMID- 14644861
TI  - Sequence variations in the collagen IX and XI genes are associated with
      degenerative lumbar spinal stenosis.
AB  - BACKGROUND: Degenerative lumbar spinal stenosis (LSS) is usually caused by disc
      herniation or degeneration. Several genetic factors have been implicated in disc
      disease. Tryptophan alleles in COL9A2 and COL9A3 have been shown to be associated
      with lumbar disc disease in the Finnish population, and polymorphisms in the
      vitamin D receptor gene (VDR) (FokI and TaqI), the matrix metalloproteinase-3
      gene (MMP-3) and an aggrecan gene (AGC1) VNTR have been reported to be associated
      with disc degeneration. In addition, an IVS6-4 a>t polymorphism in COL11A2 has
      been found in connection with stenosis caused by ossification of the posterior
      longitudinal ligament in the Japanese population. OBJECTIVE: To study the role of
      genetic factors in LSS. METHODS: 29 Finnish probands were analysed for mutations
      in the genes coding for intervertebral disc matrix proteins, COL1A1, COL1A2,
      COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, and AGC1. VDR and MMP-3
      polymorphisms were also analysed. Sequence variations were tested in 56 Finnish
      controls. RESULTS: Several disease associated alleles were identified. A splice
      site mutation in COL9A2 leading to a premature translation termination codon and
      the generation of a truncated protein was identified in one proband, another had
      the Trp2 allele, and four others the Trp3 allele. The frequency of the COL11A2
      IVS6(-4) t allele was 93.1% in the probands and 72.3% in controls (p = 0.0016).
      The differences in genotype frequencies for this site were less significant (p =
      0.0043). CONCLUSIONS: Genetic factors have an important role in the pathogenesis
      of LSS.

PMID- 14644862
TI  - Osteocyte viability with glucocorticoid treatment: relation to histomorphometry.
AB  - BACKGROUND: Glucocorticoid induced osteoporosis is a common clinical problem.
      OBJECTIVE: To determine the pathophysiology of glucocorticoid induced
      osteoarthritis at the organ level. METHODS: Iliac crest biopsy specimens were
      obtained from nine patients receiving prednisone treatment for rheumatoid
      arthritis. Osteocyte viability and histomorphometric indices were assessed.
      RESULTS: Compared with controls, glucocorticoid treated subjects had reduced
      trabecular thickness and increased erosion. The number of viable osteocytes was
      significantly decreased in glucocorticoid treated patients compared with
      controls. CONCLUSION: The impaired bone formation, increased erosion and,
      importantly, loss of viable osteocytes are all likely to contribute to the
      increased risk of fracture in these patients.

PMID- 14644863
TI  - Infliximab therapy in patients with ankylosing spondylitis: an open label 12
      month study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of long term infliximab therapy in
      patients with severe refractory ankylosing spondylitis (AS). PATIENTS AND
      METHODS: Twenty five patients (24 male, 1 female; mean (SD) age 36.0 (10.5);
      disease duration 13.8 (8.5) years) with AS fulfilling the modified New York
      criteria for AS were investigated. Twenty two (88%) patients were HLA-B27
      positive. All patients had active axial disease (Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) >/=30/100) and C reactive protein (CRP) >/=10
      mg/l, despite adequate treatment. Intravenous infliximab (5 mg/kg) was given at
      weeks 0, 2, 6, and every eight weeks thereafter for 12 months. The primary end
      point was the reduction of the patient's global assessment of pain (GAP) by >20%
      on a 100 mm visual analogue scale. RESULTS: GAP was reduced by >20% in 23 (92%)
      patients, by 50% in 21 (84%) patients, and by 70% in 13 (52%). The change in
      BASDAI and CRP from baseline was statistically significant. The treatment was
      well tolerated with minimal side effects. One patient dropped out owing to
      inefficacy and one stopped treatment owing to an allergic reaction. CONCLUSION:
      This longer length study confirms the efficacy of infliximab and the good safety
      profile in patients with AS.

PMID- 14644864
TI  - Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis.
AB  - BACKGROUND: Peripheral neuropathy is a prominent feature of the systemic and
      secondary vasculitides. Usually, it is responsive to corticosteroids, but in
      certain cases it may be resistant to corticosteroid or immunosuppressive
      treatment, or both. OBJECTIVE: To present patients who exhibited various
      inflammatory diseases accompanied with vasculitic peripheral neuropathies for
      which intravenous immunoglobulin (IVIg) was used for treatment. METHODS: Six
      patients with Sjogren's syndrome, systemic lupus erythematosus (SLE), vaccination
      induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated
      with hepatitis C infection, or sarcoidosis were included. All developed
      vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg
      body weight). The patients were followed up for 1-5 years after this treatment.
      RESULTS: In four patients (Sjogren's syndrome, Churg-Strauss vasculitis, SLE, and
      vaccination induced vasculitis) the neuropathy resolved after IVIg treatment.
      CONCLUSION: IVIg may be beneficial in cases of resistant vasculitic peripheral
      neuropathy. IVIg should probably be considered as a sole or adjuvant treatment
      for patients with contraindications to conventional treatment, or alternatively,
      for patients in whom conventional treatment has failed.

PMID- 14644865
TI  - Serum human cartilage glycoprotein 39 as a marker of arthritis associated with
      inflammatory bowel disease.
AB  - BACKGROUND: Common blood markers of arthritis are difficult to interpret in
      arthritis associated with inflammatory bowel disease (IBD) owing to the
      coexistence of two inflammatory events. No specific serological disease marker is
      available for IBD. OBJECTIVE: To determine a value of serum human cartilage
      glycoprotein 39 (HC gp39) as a marker of arthritis associated with IBD. METHODS:
      Serum levels of HC gp39 and ultrasensitive C reactive protein (CRP) were
      determined in 121 patients with IBD: 58 without arthritis (IBD-nonA) and 63 with
      arthritis (IBD-A), and in 20 healthy controls. IBD was classified as active
      (aIBD) and non-active (naIBD), and patients with IBD-A were classified as type I,
      II, and III arthritis by clinical activity indices. RESULTS: HC gp39 was higher
      in IBD-A than in IBD-nonA (p<0.001) and controls (p<0.01), while no difference
      was found between IBD-nonA and controls. CRP was increased in both IBD-A and IBD
      nonA compared with the controls (p<0.01 and <0.05, respectively) and in aIBD-nonA
      v naIBD-nonA (p<0.05), but no difference in CRP was found between aIBD-A and
      naIBD-A. Finally, a correlation was found between the number of affected joints
      (NAJ) and HC gp39 (r = 0.6, p<0.001). DISCUSSION: Increased serum levels of HC
      gp39, which were higher in IBD-A than in IBD-nonA, suggest that this substance
      might be a marker of arthropathy in IBD. HC gp39, because of its relationship
      with NAJ in IBD-A, may also be proposed as a disease activity marker in arthritis
      associated with IBD.

PMID- 14644866
TI  - Distribution of lymphatic vessels in normal and arthritic human synovial tissues.
AB  - OBJECTIVES: To investigate the distribution of lymphatic vessels in normal,
      rheumatoid arthritis (RA) and osteoarthritis (OA) synovium. METHODS: Synovial
      tissues from 5 normal controls, 14 patients with RA, and 16 patients with OA were
      studied. Lymphatic vessels were identified by immunohistochemistry using
      antibodies directed against the lymphatic endothelial hyaluronan receptor (LYVE
      1) and recognised blood vessel endothelial markers (factor VIII, CD34, CD31).
      RESULTS: Lymphatic vessels were found in all zones of the normal, OA, and RA
      synovial membrane. Few lymphatic vessels were seen in the sublining zone in
      normal and OA synovium which did not show villous hypertrophy. However, in both
      RA synovium and OA synovium showing villous hypertrophy and a chronic
      inflammatory cell infiltrate, numerous lymphatic vessels were seen in all zones
      of the synovial membrane, including the sublining zone of the superficial
      subintima. CONCLUSIONS: Lymphatic vessels are present in normal and arthritic
      synovial tissues and are more numerous and prominent where there is oedema and an
      increase in inflammatory cells in the subintima, particularly in RA. This may
      reflect increased transport of hyaluronan and leucocyte trafficking in inflamed
      synovial tissues.

PMID- 14644867
TI  - Rituximab induces remission in refractory HCV associated cryoglobulinaemic
      vasculitis.
AB  - OBJECTIVES: To report the successful induction of remission with the monoclonal
      anti-CD20 antibody rituximab in a patient with hepatitis C virus (HCV) associated
      cryoglobulinaemic vasculitis and a non-Hodgkin's lymphoma (NHL) resistant to
      previously advocated conventional treatments. CASE REPORT: The patient was a 45
      year old woman with HCV associated cryoglobulinaemic vasculitis, with purpura,
      arthralgia, constitutional symptoms, and a polyneuropathy. A malignant NHL was
      found as underlying lymphoproliferative disease. At this stage the disease was
      refractory to interferon alpha2b and ribavirin and to subsequent
      immunosuppressive treatment with cyclophosphamide. Six rituximab infusions
      targeting the CD20 antigen on cells of the B cell lineage induced remission of
      the vasculitis. Bone marrow biopsy disclosed absence of the NHL. Remission has
      subsequently been maintained and HCV eliminated with the new pegylated interferon
      alpha2b and ribavirin for nearly one year. CONCLUSIONS: Transition of the
      underlying "benign" lymphoproliferative disease to a malignant lymphoma may
      result in difficult to treat HCV associated cryoglobulinaemic vasculitis.
      Rituximab offers a new possibility for inducing remission in refractory HCV
      associated cryoglobulinaemic vasculitis and the lymphoproliferative disorder.
      After remission, HCV may subsequently be eliminated with pegylated interferon
      alpha2b and ribavirin.

PMID- 14644868
TI  - Sexual dimorphism in the osteoarthritis of STR/ort mice may be linked to
      articular cytokines.
AB  - BACKGROUND: STR/ort mice spontaneously develop degenerative changes of the knee
      joints resembling human osteoarthritis (OA), with the males being more severely
      affected than the females. OBJECTIVE: To analyse the early changes leading to OA
      by examining the articular cytokine expression and degenerative changes in
      STR/ort mice. METHODS: 122 STR/ort mice of both sexes aged between 2 and 15.5
      months were included. Thin sections of the knees were analysed for osteoarthritic
      changes by haematoxylin/eosin staining. The articular cytokine expression was
      investigated by immunohistochemical staining using monoclonal antibodies specific
      for interleukin (IL)6, tumour necrosis factor alpha, transforming growth factor
      beta1 (TGFbeta1), IL1beta, IL4, and IL10, respectively. RESULTS: Both cartilage
      degeneration and articular cytokine expression differ between the sexes. The
      protection from cartilage degeneration in the female mice correlates with an
      increased expression of TGFbeta1 and IL4 at 2 months of age. CONCLUSION: The
      increased expression of TGFbeta1 and IL4 in young STR/ort female mice suggests
      that the sexual dimorphism is mediated through the articular expression of
      cytokines involved in cartilage metabolism.

PMID- 14644869
TI  - Involvement of the omentum in Wegener's granulomatosis.

PMID- 14644870
TI  - Infliximab in refractory spondyloarthropathies: a multicentre 38 week open study.

PMID- 14644871
TI  - High incidence of hepatotoxicity of isoniazid treatment for tuberculosis
      chemoprophylaxis in patients with rheumatoid arthritis treated with methotrexate
      or sulfasalazine and anti-tumour necrosis factor inhibitors.

PMID- 14644872
TI  - Insurance problems among patients with ankylosing spondylitis.

PMID- 14644873
TI  - Anti-tumour necrosis factor alpha treatment in chronic recurrent inflammation of
      the anterior segment of the eye in patients resistant to standard
      immunomodulatory treatment.

PMID- 14644874
TI  - Syncope in a patient with relapsing polychondritis.

PMID- 14644890
TI  - Test performance of positron emission tomography and computed tomography for
      mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis.
AB  - PURPOSE: To compare the diagnostic accuracy of computed tomography (CT) and
      positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) for
      mediastinal staging in patients with non-small-cell lung cancer and to determine
      whether test results are conditionally dependent (the sensitivity and specificity
      of FDG-PET depend on the presence or absence of enlarged mediastinal lymph nodes
      on CT). DATA SOURCES: Computerized search of MEDLINE, EMBASE, BIOSIS, and
      CancerLit through March 2003 and reference lists of retrieved studies and review
      articles. STUDY SELECTION: Studies in any language that examined FDG-PET for
      mediastinal staging in patients with known or suspected non-small-cell lung
      cancer, enrolled at least 10 participants (including at least 5 participants with
      mediastinal metastasis), and provided enough data to permit calculation of
      sensitivity and specificity for identifying lymph node involvement. DATA
      EXTRACTION: One reviewer (of non-English-language studies) or 2 reviewers (of
      English-language studies) independently evaluated studies for inclusion, rated
      methodologic quality, and abstracted relevant data. DATA SYNTHESIS: Thirty-nine
      studies met inclusion criteria. Methodologic quality varied, but few aspects of
      study quality affected diagnostic accuracy. The authors constructed summary
      receiver-operating characteristic curves for CT and FDG-PET. Positron emission
      tomography with 18-fluorodeoxyglucose was more accurate than CT for identifying
      lymph node involvement (P < 0.001). For CT, median sensitivity and specificity
      were 61% (interquartile range, 50% to 71%) and 79% (interquartile range, 66% to
      89%), respectively. For FDG-PET, median sensitivity and specificity were 85%
      (interquartile range, 67% to 91%) and 90% (interquartile range, 82% to 96%),
      respectively. Fourteen studies provided information about the conditional test
      performance of CT and FDG-PET. Positron emission tomography with 18
      fluorodeoxyglucose was more sensitive but less specific when CT showed enlarged
      lymph nodes (median sensitivity, 100% [interquartile range, 90% to 100%]; median
      specificity, 78% [interquartile range, 68% to 100%]) than when CT showed no lymph
      node enlargement (median sensitivity, 82% [interquartile range, 65% to 100%];
      median specificity, 93% [interquartile range, 92% to 100%]; P = 0.002).
      CONCLUSIONS: Positron emission tomography with 18-fluorodeoxyglucose is more
      accurate than CT for mediastinal staging. Positron emission tomography with 18
      fluorodeoxyglucose is more sensitive but less specific when CT shows enlarged
      mediastinal lymph nodes.

PMID- 14644891
TI  - Clinical impact of bleeding in patients taking oral anticoagulant therapy for
      venous thromboembolism: a meta-analysis.
AB  - BACKGROUND: Clinicians should consider the clinical impact of anticoagulant
      related bleeding when deciding on the duration of anticoagulant therapy in
      patients with venous thromboembolism. PURPOSE: To provide reliable estimates of
      the clinical impact of anticoagulant-related bleeding, defined as the case
      fatality rate of major bleeding and the risk for intracranial bleeding. DATA
      SOURCES: MEDLINE (January 1989 to May 2003), Cochrane Controlled Trial Registry,
      thromboembolism experts, and reference lists; English-language literature only.
      STUDY SELECTION: Randomized, controlled trials and prospective cohort studies
      that investigated patients with venous thromboembolism who received oral
      anticoagulant therapy (target international normalized ratio, 2.0 to 3.0) for at
      least 3 months and that reported major bleeding and death as primary study
      outcomes. DATA EXTRACTION: Two reviewers independently extracted data on the
      number of anticoagulant-related major and intracranial bleeding episodes and on
      whether these events were fatal or nonfatal. DATA SYNTHESIS: The authors analyzed
      33 studies involving 4374 patient-years of oral anticoagulant therapy. For all
      patients, the case-fatality rate of major bleeding was 13.4% (95% CI, 9.4% to
      17.4%) and the rate of intracranial bleeding was 1.15 per 100 patient-years (CI,
      1.14 to 1.16 per 100 patient-years). For patients who received anticoagulant
      therapy for more than 3 months, the case-fatality rate of major bleeding was 9.1%
      (CI, 2.5% to 21.7%), and the rate of intracranial bleeding was 0.65 per 100
      patient-years (CI, 0.63 to 0.68 per 100 patient-years) after the initial 3 months
      of anticoagulation. CONCLUSION: The clinical impact of anticoagulant-related
      major bleeding in patients with venous thromboembolism is considerable, and
      clinicians should take this into account when deciding whether to continue long
      term oral anticoagulant therapy in an individual patient.

PMID- 14644892
TI  - Albuminuria and cardiovascular risk in hypertensive patients with left
      ventricular hypertrophy: the LIFE study.
AB  - BACKGROUND: Several studies have shown that albuminuria is associated with
      increased risk for fatal and nonfatal cardiovascular events, independent of
      conventional risk factors. The partition values for urine albumin-creatinine
      ratio (UACR) used to identify microalbuminuria have been based on studies that
      predicted risk in diabetic patients. OBJECTIVE: To determine whether the relation
      between albuminuria and cardiovascular risk can be used to predict cardiovascular
      morbidity and mortality in hypertensive patients. DESIGN: Multicenter cohort
      study derived from a randomized, controlled trial. PATIENTS: 8206 patients with
      stage II or III hypertension randomly assigned to double-blind therapy with
      losartan or atenolol. Follow-up was 39 122 patient-years. MEASUREMENTS: Renal
      glomerular permeability evaluated by UACR. RESULTS: In nondiabetic hypertensive
      patients with left ventricular hypertrophy, the risk for the composite
      cardiovascular end point increased continuously as albuminuria increased (P <
      0.001 for trend). There was no specific threshold for increased risk. For every
      10-fold increase in UACR, hazard ratios in nondiabetic patients increased as
      follows: composite end point, by 57% (95% CI, 40.6% to 75.0%); cardiovascular
      mortality, by 97.7% (CI, 66.5% to 235%); all-cause mortality, by 75.2% (CI, 54.0%
      to 99.4%); stroke, by 51.0% (CI, 28.8% to 76.9%); and myocardial infarction, by
      45% (CI, 19.9% to 75.4%) (P < 0.001 for all comparisons). Values were similar in
      diabetic patients, although for myocardial infarction the trend was weaker and
      not significant. CONCLUSION: Increased UACR resulted in increasing risk for
      cardiovascular morbidity and mortality among hypertensive patients with left
      ventricular hypertrophy. We found no thresholds or plateaus. Risk increases at
      much lower UACR values than has been reported among diabetic patients.

PMID- 14644893
TI  - Patient-centered communication, ratings of care, and concordance of patient and
      physician race.
AB  - BACKGROUND: African-American patients who visit physicians of the same race rate
      their medical visits as more satisfying and participatory than do those who see
      physicians of other races. Little research has investigated the communication
      process in race-concordant and race-discordant medical visits. OBJECTIVES: To
      compare patient-physician communication in race-concordant and race-discordant
      visits and examine whether communication behaviors explain differences in patient
      ratings of satisfaction and participatory decision making. DESIGN: Cohort study
      with follow-up using previsit and postvisit surveys and audiotape analysis.
      SETTING: 16 urban primary care practices. PATIENTS: 252 adults (142 African
      American patients and 110 white patients) receiving care from 31 physicians (of
      whom 18 were African-American and 13 were white). MEASUREMENTS: Audiotape
      measures of patient-centeredness, patient ratings of physicians' participatory
      decision-making styles, and overall satisfaction. RESULTS: Race-concordant visits
      were longer (2.15 minutes [95% CI, 0.60 to 3.71]) and had higher ratings of
      patient positive affect (0.55 point, [95% CI, 0.04 to 1.05]) compared with race
      discordant visits. Patients in race-concordant visits were more satisfied and
      rated their physicians as more participatory (8.42 points [95% CI, 3.23 to
      13.60]). Audiotape measures of patient-centered communication behaviors did not
      explain differences in participatory decision making or satisfaction between race
      concordant and race-discordant visits. CONCLUSIONS: Race-concordant visits are
      longer and characterized by more patient positive affect. Previous studies link
      similar communication findings to continuity of care. The association between
      race concordance and higher patient ratings of care is independent of patient
      centered communication, suggesting that other factors, such as patient and
      physician attitudes, may mediate the relationship. Until more evidence is
      available regarding the mechanisms of this relationship and the effectiveness of
      intercultural communication skills programs, increasing ethnic diversity among
      physicians may be the most direct strategy to improve health care experiences for
      members of ethnic minority groups.

PMID- 14644894
TI  - Update in hematology.

PMID- 14644895
TI  - The discrepancy between observational studies and randomized trials of menopausal
      hormone therapy: did expectations shape experience?
AB  - Differences between observational and randomized studies of the effects of
      menopausal hormone therapy (HT) on coronary heart disease (CHD) have been
      attributed to the fact that women who choose to use HT tend to be healthier than
      those who do not. Although this bias should affect all clinical outcomes with
      modifiable risk factors, estimates for stroke and pulmonary embolism were
      unaffected. The authors sought possible explanations for this isolated
      discrepancy in CHD findings. Unlike the randomized Women's Health Initiative
      (WHI) trial, the observational Nurses' Health Study (NHS) did not try to detect
      silent myocardial infarctions. Many women present with atypical ischemic
      symptoms. Hormone therapy users who believe that HT reduces CHD risks might not
      interpret ischemic symptoms as related to CHD, might not seek medical attention,
      and might present differently to their physicians, all of which could lead to
      more unrecognized myocardial infarctions among HT users in the NHS. In addition,
      persons completing death certificates and NHS physicians interpreting death
      certificates were not blinded to the use of HT. If persons assigning cause of
      death knew the patient had used HT and believed that HT prevented CHD, they might
      have been more likely to assign a condition other than CHD as the cause of death.
      If HT users were 20% less likely to have their infarctions recognized and their
      deaths attributed to CHD, a true increase in CHD due to HT use would appear to be
      a reduction in CHD. Combining these reporting biases with socioeconomic
      differences between users and nonusers could explain discrepancies. Beliefs held
      by patients, clinicians, and investigators might have affected the ascertainment
      of CHD outcomes in observational studies.

PMID- 14644896
TI  - Screening for obesity in adults: recommendations and rationale.
AB  - This statement summarizes the U.S. Preventive Services Task Force (USPSTF)
      recommendations on screening for obesity in adults based on the USPSTF's
      examination of evidence specific to obesity and overweight in adults and updates
      the 1996 recommendations on this topic. The complete USPSTF recommendation and
      rationale statement on this topic, which includes a brief review of the
      supporting evidence, is available through the USPSTF Web site
      (http://www.preventiveservices.ahrq.gov), the National Guideline Clearinghouse
      (http://www.guideline.gov), and in print through the Agency for Healthcare
      Research and Quality Publications Clearinghouse (telephone, 800-358-9295; e-mail,
      ahrqpubs@ahrq.gov). The complete information on which this statement is based,
      including evidence tables and references, is available in the accompanying
      article in this issue and in the summary of the evidence and systematic evidence
      review on the Web sites already mentioned. The summary of the evidence is also
      available in print through the Agency for Healthcare Research and Quality
      Publications Clearinghouse. *For a list of the members of the U.S. Preventive
      Services Task Force, see the Appendix.

PMID- 14644898
TI  - New diagnostic tests: breakthrough approaches or expensive add-ons?

PMID- 14644897
TI  - Screening and interventions for obesity in adults: summary of the evidence for
      the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Obesity poses a considerable and growing health burden. This review
      examines evidence for screening and treating obesity in adults. DATA SOURCES:
      MEDLINE and Cochrane Library (January 1994 through February 2003). STUDY
      SELECTION: Systematic reviews; randomized, controlled trials; and observational
      studies of obesity's health outcomes or efficacy of obesity treatment. DATA
      EXTRACTION: Two reviewers independently abstracted data on study design, sample,
      sample size, treatment, outcomes, and quality. DATA SYNTHESIS: No trials
      evaluated mass screening for obesity, so the authors evaluated indirect evidence
      for efficacy. Pharmacotherapy or counseling interventions produced modest
      (generally 3 to 5 kg) weight loss over at least 6 or 12 months, respectively.
      Counseling was most effective when intensive and combined with behavioral
      therapy. Maintenance strategies helped retain weight loss. Selected surgical
      patients lost substantial weight (10 to 159 kg over 1 to 5 years). Weight
      reduction improved blood pressure, lipid levels, and glucose metabolism and
      decreased diabetes incidence. The internal validity of the treatment trials was
      fair to good, and external validity was limited by the minimal ethnic or gender
      diversity of volunteer participants. No data evaluated counseling harms. Primary
      adverse drug effects included hypertension with sibutramine (mean increase, 0 mm
      Hg to 3.5 mm Hg) and gastrointestinal distress with orlistat (1% to 37% of
      patients). Fewer than 1% (pooled samples) of surgical patients died; up to 25%
      needed surgery again over 5 years. CONCLUSIONS: Counseling and pharmacotherapy
      can promote modest sustained weight loss, improving clinical outcomes.
      Pharmacotherapy appears safe in the short term; long-term safety has not been as
      strongly established. In selected patients, surgery promotes large amounts of
      weight loss with rare but sometimes severe complications.

PMID- 14644899
TI  - Moving beyond black and white.

PMID- 14644900
TI  - Risk factors and secondary prevention in women with heart disease.

PMID- 14644901
TI  - Diagnostic and prognostic testing in pneumonia.

PMID- 14644902
TI  - Helical computed tomography as a test for pulmonary embolism.

PMID- 14644903
TI  - Nonconvulsive status epilepticus resulting from benzodiazepine withdrawal.

PMID- 14644904
TI  - A decree against inappropriate medical care in Italy.

PMID- 14644905
TI  - Summaries for patients. Detecting spread of non-small-cell lung cancer within the
      chest.

PMID- 14644906
TI  - Summaries for patients. Consequences of serious bleeding complications from
      warfarin.

PMID- 14644907
TI  - Summaries for patients. Microalbuminuria increases risk for heart attacks and
      strokes in hypertensive patients.

PMID- 14644908
TI  - Summaries for patients. Communication in health care visits when doctors and
      patients have the same versus different ethnic backgrounds.

PMID- 14644909
TI  - Summaries for patients. Screening for obesity in adults: recommendations from the
      U.S. Preventive Services Task Force.

PMID- 14644910
TI  - Coronary artery disease and the acute coronary syndrome.

PMID- 14644911
TI  - Peginterferon-based therapy for chronic hepatitis C virus infection in patients
      with normal alanine aminotransferase levels.

PMID- 14644913
TI  - Pollinarium morphology and floral rewards in Brazilian Maxillariinae
      (Orchidaceae).
AB  - BACKGROUND AND AIMS: There is strong support for the monophyly of the orchid
      subtribe Maxillariinae s.l., yet generic boundaries within it are unsatisfactory
      and need re-evaluation. In an effort to assemble sets of morphological characters
      to distinguish major clades within this subtribe, the pollinarium morphology and
      floral rewards of representative Brazilian species of this subtribe were studied.
      METHODS: The study was based on fresh material from 60 species and seven genera
      obtained from cultivated specimens. Variation of pollinarium structure and floral
      rewards was assessed using a stereomicroscope and by SEM analysis. KEY RESULTS:
      Four morphological types of pollinaria are described. Type 1 appears to be the
      most widespread and is characterized by a well-developed tegula. Type 2 lacks a
      stipe and the pollinia are attached directly to the viscidium. Type 3 also lacks
      a stipe, and the viscidium is rigid and dark. In Type 4, the stipe consists of
      the whole median rostelar portion and, so far, is known only from Maxillaria
      uncata. Nectar, trichomes, wax-like and resin-like secretions are described as
      flower rewards for different groups of species within the genus Maxillaria. Data
      on the biomechanics and pollination biology are also discussed and illustrated.
      In Maxillariinae flowers with arcuate viscidia, the pollinaria are deposited on
      the scuttellum of their Hymenopteran pollinators. In contrast, some flowers with
      rounded to rectangular, pad-like viscidia fix their pollinaria on the face of
      their pollinators. CONCLUSIONS: Pollinarium morphology and floral features
      related to pollination in Brazilian Maxillariinae are more diverse than
      previously suggested. It is hoped that the data presented herein, together with
      other data sources such as vegetative traits and molecular tools, will be helpful
      in redefining and diagnosing clades within the subtribe Maxillariinae.

PMID- 14644912
TI  - Evolution of c4 phosphoenolpyruvate carboxylase. Genes and proteins: a case study
      with the genus Flaveria.
AB  - C4 photosynthesis is characterized by a division of labour between two different
      photosynthetic cell types, mesophyll and bundle-sheath cells. Relying on
      phosphoenolpyruvate carboxylase (PEPC) as the primary carboxylase in the
      mesophyll cells a CO2 pump is established in C4 plants that concentrates CO2 at
      the site of ribulose 1,5-bisphosphate carboxylase/oxygenase in the bundle-sheath
      cells. The C4 photosynthetic pathway evolved polyphyletically implying that the
      genes encoding the C4 PEPC originated from non-photosynthetic PEPC progenitor
      genes that were already present in the C3 ancestral species. The dicot genus
      Flaveria (Asteraceae) is a unique system in which to investigate the molcular
      changes that had to occur in order to adapt a C3 ancestral PEPC gene to the
      special conditions of C4 photosynthesis. Flaveria contains not only C3 and C4
      species but also a large number of C3-C4 intermediates which vary to the degree
      in which C4 photosynthetic traits are expressed. The C4 PEPC gene of Flaveria
      trinervia, which is encoded by the ppcA gene class, is highly expressed but only
      in mesophyll cells. The encoded PEPC protein possesses the typical kinetic and
      regulatory features of a C4-type PEPC. The orthologous ppcA gene of the C3
      species Flaveria pringlei encodes a typical non-photosynthetic, C3-type PEPC and
      is weakly expressed with no apparent cell or organ specificity. PEPCs of the ppcA
      type have been detected also in C3-C4 intermediate Flaveria species. These
      orthologous PEPCs have been used to determine the molecular basis for C4 enzyme
      characteristics and to understand their evolution. Comparative and functional
      analyses of the ppcA promoters from F. trinervia and F. pringlei make it possible
      to identity the cis-regulatory sequences for mesophyll-specific gene expression
      and to search for the corresponding trans-regulatory factors.

PMID- 14644914
TI  - The impact of pH and calcium on the uptake of fluoride by tea plants (Camellia
      sinensis L.).
AB  - BACKGROUND AND AIMS: Tea plants (Camellia sinensis L.) accumulate large amounts
      of fluoride (F) from soils containing normal F concentrations. The present
      experiments examined the effects of pH and Ca on F uptake by this accumulating
      plant species. METHODS: The effect of pH was assessed in two experiments, one
      using uptake solutions with different pHs, and the other using lime, as CaO,
      applied to the soil. The effect of Ca was examined by analysing F concentrations
      in plants supplied with varying amounts of Ca, as Ca(NO3)2, either in uptake
      solutions or through the soil. KEY RESULTS: F uptake was highest at solution pH
      5.5, and significantly lower at pH 4.0. In the soil experiment, leaf F decreased
      linearly with the amounts of lime, which raised the soil pH progressively from
      4.32 to 4.91, 5.43, 5.89 and, finally, 6.55. Liming increased the water-soluble F
      content of the soil. Including Ca in the uptake solution or adding Ca to soil
      significantly decreased leaf F concentrations. The distribution pattern of F in
      tea plants was not altered by Ca treatment, with most F being allocated to
      leaves. The activity of F- in the uptake solution was unaffected and water
      soluble F in the soil was sometimes increased by added Ca. CONCLUSIONS: F uptake
      by tea plants, which are inherently able to accumulate large quantities of F, was
      affected both by pH and by Ca levels in the medium. The reduced F uptake
      following Ca application appeared not to be due simply to the precipitation of
      CaF2 in solution and soil or to the complexing of Ca and F in roots, although
      these factors cannot be dismissed. It was more likely due to the effect of Ca on
      the properties of cell wall or membrane permeability in the solution experiments,
      and to alteration of F speciations and their quantities in soil solutions
      following Ca application.

PMID- 14644915
TI  - A common pathway for the uptake of surfactant lipids by alveolar cells.
AB  - The uptake of different surfactant lipids-dipalmitoylphosphatidylcholine (DPPC),
      phosphatidylglycerol (PG), or phosphatidylinositol (PI)-and liposomes with a
      surfactant-like composition by alveolar type II cells (alveolar type II cells)
      and macrophages (alveolar macrophages) was studied in vitro. Fluorescent-labeled
      liposomes containing either 86% of the studied lipid, i.e., DPPC, PG, PI, and 6%
      labeled phosphatidylethanolamine (PE) and 8% cholesterol or a lipid mixture
      similar to surfactant (DPPC, PG, PI, phosphatidylcholine, PE, and cholesterol in
      a weight ratio of 55:8:2:21:8:6) were incubated with alveolar macrophages and
      alveolar type II cells. The cell-associated fluorescence assessed by flow
      cytometry demonstrated a higher uptake of PG and PI by both alveolar macrophages
      and alveolar type II cells, and a lower uptake of DPPC by alveolar macrophages.
      In addition, fewer alveolar type II cells take up DPPC, whereas there are no
      differences for the alveolar macrophages in the number of cells involved in the
      uptake. Competition experiments with Texas Red-labeled liposomes and either DPPC
      liposomes or PI liposomes labeled with Bodipy indicated that all these liposomes
      are internalized via the same pathway by alveolar cells. Thus, lipid composition
      directly influences the (re)uptake of surfactant.

PMID- 14644916
TI  - Sounding the mediastinum.

PMID- 14644917
TI  - Impaired arousals and sudden infant death syndrome: preexisting neural injury?

PMID- 14644918
TI  - Bronchoscopic sampling of drug concentrations: penetration to tissue is the
      issue.

PMID- 14644919
TI  - Smoking: a neglected cause of glucocorticoid resistance in asthma.

PMID- 14644920
TI  - Development of fluoroquinolones as first-line drugs for tuberculosis--at long
      last!

PMID- 14644921
TI  - The matrix unloaded: aerosolized heparin or urokinase for pulmonary fibrosis.

PMID- 14644922
TI  - Hemodynamic instability in sepsis: bedside assessment by Doppler
      echocardiography.

PMID- 14644923
TI  - Bronchiolar disorders.
AB  - Bronchiolar abnormalities are relatively common and occur in a variety of
      clinical settings. Various histopathologic patterns of bronchiolar injury have
      been described and have led to confusing nomenclature with redundant and
      overlapping terms. Some histopathologic patterns of bronchiolar disease may be
      relatively unique to a specific clinical context but others are nonspecific with
      respect to either etiology or pathogenesis. Herein, we present a scheme
      separating (1) those disorders in which the bronchiolar disease is the
      predominant abnormality (primary bronchiolar disorders) from (2) parenchymal
      disorders with prominent bronchiolar involvement and (3) bronchiolar involvement
      in large airway diseases. Primary bronchiolar disorders include constrictive
      bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans), acute
      bronchiolitis, diffuse panbronchiolitis, respiratory bronchiolitis, mineral dust
      airway disease, follicular bronchiolitis, and a few other rare variants.
      Prominent bronchiolar involvement may be seen in several interstitial lung
      diseases, including hypersensitivity pneumonitis, respiratory bronchiolitis
      associated interstitial lung disease, cryptogenic organizing pneumonia
      (idiopathic bronchiolitis obliterans organizing pneumonia), and pulmonary
      Langerhans' cell histiocytosis. Large airway diseases that commonly involve
      bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary
      disease. The clinical relevance of a bronchiolar lesion is best determined by
      identifying the underlying histopathologic pattern and assessing the correlative
      clinico-physiologic-radiologic context.

PMID- 14644924
TI  - Reversal of allergic airway hyperreactivity after long-term allergen challenge
      depends on gammadelta T cells.
AB  - Long-term allergen exposure can attenuate inflammation and revert airway
      hyperreactivity to normal responsiveness. A model of such reversal was
      established in which airway hyperreactivity and inflammation in ovalbumin
      sensitized and challenged mice were decreased after multiple daily airway
      challenges. This change in responsiveness and inflammation was associated with a
      transition from a helper T cell Type 2 to a helper T cell Type 1 cytokine-biased
      profile in bronchoalveolar lavage fluid. Cell transfer from long-term exposed
      mice into hyperreactive mice also restored normal airway responsiveness,
      establishing the mechanism underlying the reversal of the hyperreactivity as
      active suppression, but did not affect eosinophilic airway inflammation.
      Conversely, airway hyperreactivity, suppressed as a result of long-term allergen
      exposure, could be reestablished by depleting gammadelta T cells, in particular
      Vgamma4+ cells. Antigen-specific tolerance of alphabeta T cells or suppression by
      non-gammadelta T cells did not play a role in the reversal to normal airway
      responsiveness and gammadelta T cells did not play a role in the regulation of
      the allergic inflammatory response. These findings show that normal
      responsiveness in previously hyperreactive mice, achieved after long-term
      allergen challenge, is based on several, apparently independent regulatory
      mechanisms. One of these, focused on airway responsiveness, involves active
      suppression and requires gammadelta T cells.

PMID- 14644925
TI  - Prevention of bleomycin-induced lung fibrosis by aerosolization of heparin or
      urokinase in rabbits.
AB  - Bleomycin is a well known fibrogenic agent, provoking an initial adult
      respiratory distress syndrome-like injury with subsequent strong
      fibroproliferative response. Severe abnormalities of the alveolar surfactant
      system, which may be linked to the appearance of alveolar fibrin deposition, have
      been implicated in the pathogenetic sequence of events. Using a model of
      standardized aerosol delivery of 1.8 U bleomycin/kg body weight in rabbits, we
      investigated the influence of repetitive nebulization of heparin or urokinase
      type plasminogen activator (u-PA) on the development of lung fibrosis. In an
      "early" (Days 2-12 postbleomycin) or "late" (Days 14-24 post-bleomycin) treatment
      protocol, approximately 3,500 U heparin or approximately 6,500 U u-PA was
      delivered to the bronchoalveolar space. Within four weeks, the bleomycin
      challenge provoked severe pulmonary fibrosis with reduction of lung compliance,
      marked increase in soluble collagen (bronchoalveolar lavage fluid) and
      hydroxyproline content (lung tissue), a typical reticular fibrosis pattern on
      high-resolution computed tomography, and typical histologic findings. Therapeutic
      intervention resulted in a far-reaching normalization of compliance, suppression
      of soluble collagen and hydroxyproline accumulation, and virtual abrogation of
      the computed tomography scan and histologic features of lung fibrosis, with most
      prominent effects seen in the early heparin and late u-PA administration. No
      bleeding complications occurred. These findings strongly support the concept that
      alveolar fibrin generation is an important event in the development of
      postbleomycin lung fibrosis. "Compartmentalized" anticoagulation and/or
      fibrinolysis via inhalational deposition of interventional agents in the alveolar
      compartment may thus offer a new therapeutic strategy for prevention of fibrosis.

PMID- 14644926
TI  - Effects of therapeutic hypercapnia on mesenteric ischemia-reperfusion injury.
AB  - Hypercapnic acidosis protects against direct lung injury in in vivo and ex vivo
      models, however, lung injury/acute respiratory distress syndrome commonly occurs
      after a nonpulmonary etiology. We investigated whether therapeutic hypercapnia
      (TH)-deliberate elevation of carbon dioxide (CO2) tension-would protect against
      lung injury after splanchnic ischemia-reperfusion injury in an in vivo model. TH
      was associated with preservation of lung mechanics, attenuation of protein
      leakage, and improved oxygenation compared with control conditions. Lung
      protection was therapeutic as well as prophylactic. Protection was dose
      dependent, but inspired CO2 concentrations above 5.0% were associated with little
      additional lung protection. Before lung injury, increasing FICO2 resulted in a
      dose-dependent increase in PaO2. Lung protection with hypercapnia occurred
      despite pulmonary artery pressures that were greater than observed with
      normocapnia. Reperfusion increased lipid peroxidation (tissue 8-isoprostane
      concentration) in the bowel, liver, and lung, and caused histologically apparent
      bowel injury; however, none of these effects was altered by TH. Therefore, TH
      induced by adding CO2 to inspired gas-provides consistent protection against lung
      injury in terms of lung permeability, oxygenation, and lung mechanics after
      mesenteric ischemia-reperfusion. These data further support the emerging evidence
      for ongoing physiologic study of TH at the bedside.

PMID- 14644927
TI  - ATS, American Bar Association, and asbestos.

PMID- 14644929
TI  - Natural porcine surfactant augments airway inflammation after allergen challenge
      in patients with asthma.
AB  - There is increasing evidence for a role of pulmonary surfactant in asthma and
      allergic inflammation. In murine asthma models, recent studies have demonstrated
      that surfactant components downregulate the allergic inflammation. Therefore, we
      tested the hypothesis that in individuals with mild asthma, a natural porcine
      surfactant preparation (Curosurf) given before segmental allergen challenge can
      reduce the allergic airway inflammation. Ten patients with asthma and five
      healthy control subjects were treated in two segments with either Curosurf or
      vehicle followed by local allergen challenge. Six additional patients with asthma
      received Curosurf before allergen challenge in one segment as above, but the
      second segment was instilled with Curosurf without allergen challenge.
      Unexpectedly, surfactant treatment augmented the eosinophilic inflammation 24
      hours after allergen challenge. A direct chemotactic effect of Curosurf was
      excluded. However, levels of eotaxin and interleukin-5 were increased in
      bronchoalveolar lavage after Curosurf treatment, whereas IFN-gamma-levels and
      numbers of IFN-gamma(+) T cells were decreased. Curosurf had no influence on
      spreading and retention of allergen determined by allergen uptake in mice. These
      findings demonstrate that treatment with a natural porcine surfactant results in
      an augmentation of the eosinophilic inflammation after allergen challenge that is
      more likely due to immunomodulatory effects than to biophysical properties of the
      surfactant.

PMID- 14644930
TI  - Ventilation-induced neutrophil infiltration depends on c-Jun N-terminal kinase.
AB  - Positive pressure ventilation with large VTs has been shown to cause release of
      cytokines, including macrophage inflammatory protein-2 (MIP-2), a functional
      equivalent of human interleukin-8. The mechanisms regulating ventilation-induced
      cytokine production are unclear. Based on our previous in vitro model of lung
      cell stretch, we hypothesized that high VT ventilation-induced MIP-2 production
      is dependent on the activation of the c-Jun N-terminal kinase (JNK). We exposed
      C57BL/6 mice to high VT (30 ml/kg) or low VT (6 ml/kg) mechanical ventilation for
      5 hours. High VT ventilation-induced neutrophil migration into the lung, MIP-2
      protein production, MIP-2 messenger RNA expression, and JNK activation. Large VT
      ventilation of JNK knockout mice and pharmacologic JNK inhibition with SP600125
      attenuated neutrophil sequestration and blocked MIP-2 messenger RNA expression
      and MIP-2 production. We conclude that lung cell stretch in vivo results in
      increased lung neutrophil sequestration and increased MIP-2 production, which
      was, at least in part, dependent upon the JNK pathway.

PMID- 14644931
TI  - Overexpression of placenta growth factor contributes to the pathogenesis of
      pulmonary emphysema.
AB  - To examine the role of placenta growth factor (PlGF) in the pathogenesis of
      pulmonary emphysema, we generated PlGF-transgenic (TG) mice using a
      phosphoglycerate kinase promoter. This resulted in constitutive overexpression of
      PlGF. In these TG mice, pulmonary emphysema, with enlarged air spaces and
      enhanced pulmonary compliance, first appeared at 6 months of age and became
      prominent at 12 months. Increased alveolar septal cell apoptosis was noted in
      their lungs. Fluorescence-activated cell sorter analysis suggests that these
      apoptotic septal cells are type II pneumocytes. At the same time, the messenger
      RNA of vascular endothelial growth factor and platelet-endothelial cell adhesion
      molecule-1, an endothelial cell marker, were downregulated indicating a reduced
      number of endothelial cells and its survival factor VEGF. In vitro, exogenous
      PlGF can inhibit the proliferation and promote the cell death of mouse type II
      pneumocytes. In normal newborn mice, abundant expression of PlGF messenger RNA
      was detected in the lungs during saccular division but was rapidly downregulated
      after alveolarization was complete. Thus, a persistently elevated PlGF was
      detrimental to the developed lung and causes the emphysematous change seen in our
      TG mice. Our study suggests that PlGF plays an important role in the pathogenesis
      of pulmonary emphysema via its action on type II pneumocytes.

PMID- 14644932
TI  - Passive smoke effects on cough and airways in young guinea pigs: role of
      brainstem substance P.
AB  - Children raised with extended exposure to environmental tobacco smoke (ETS)
      experience increased cough and wheeze. This study was designed to determine
      whether extended ETS exposure enhances citric acid-induced cough and
      bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor
      mechanism at the first central synapse of lung afferent neurons, the nucleus
      tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At
      5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus
      tractus solitarius at a site that produced apnea in response to the glutamate
      agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1
      receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius
      of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS
      exposure significantly enhanced citric acid-induced cough by 56% and maximal Penh
      (a measure of airway obstruction) by 43%, effects that were attenuated by the NK
      1 receptor antagonist in the nucleus tractus solitarius. We conclude that in
      young guinea pigs extended exposure to ETS increases citric acid-induced cough
      and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus
      tractus solitarius.

PMID- 14644933
TI  - Diagnosing asthma: comparisons between exhaled nitric oxide measurements and
      conventional tests.
AB  - International guidelines recommend a range of clinical tests to confirm the
      diagnosis of asthma. These focus largely on identifying variable airflow
      obstruction and responses to bronchodilator or corticosteroid. More recently,
      exhaled nitric oxide (FE(NO)) measurements and induced sputum analysis to assess
      airway inflammation have been highlighted. However, to date, no systematic
      comparisons to confirm the diagnostic utility of each of these methods have been
      performed. To do so, we investigated 47 consecutive patients with symptoms
      suggestive of asthma, using a comprehensive fixed-sequence series of diagnostic
      tests. Sensitivities and specificities were obtained for peak flow measurements,
      spirometry, and changes in these parameters after a trial of steroid. Comparisons
      were made against FE(NO) and sputum cell counts. Sensitivities for each of the
      conventional tests (0-47%) were lower than for FE(NO) (88%) and sputum
      eosinophils (86%). Overall, the diagnostic accuracy when using FE(NO) and sputum
      eosinophils was significantly greater. Results for conventional tests were not
      improved, using a trial of steroid. We conclude that FE(NO) measurements and
      induced sputum analysis are superior to conventional approaches, with exhaled
      nitric oxide being most advantageous because the test is quick and easy to
      perform.

PMID- 14644934
TI  - What do we gain from the sixth coronary heart disease drug?

PMID- 14644935
TI  - Risk factor scoring for coronary heart disease.

PMID- 14644936
TI  - Is the NHS getting better or worse?

PMID- 14644937
TI  - Lessons for the NHS from Kaiser Permanente.

PMID- 14644938
TI  - Should we be screening for and treating amblyopia?

PMID- 14644939
TI  - Treatments for heavy menstrual bleeding.

PMID- 14644940
TI  - Report predicts 20 million AIDS orphans in Africa by 2010.

PMID- 14644941
TI  - Nearly 50 000 adults in the United Kingdom now have HIV.

PMID- 14644942
TI  - Global efforts to control AIDS are "entirely inadequate".

PMID- 14644943
TI  - South Africa introduces world's largest AIDS treatment plan.

PMID- 14644945
TI  - NICE recommends faster, easier access to care for MS patients.

PMID- 14644947
TI  - MEPs approve stem cell research using human embryos.

PMID- 14644953
TI  - Mentally ill patients in central Europe being kept in padlocked, caged beds.

PMID- 14644954
TI  - Neonatal deaths hamper India's infant mortality targets.

PMID- 14644955
TI  - Nuffield Trust praises ambitious NHS plans but calls for better monitoring.

PMID- 14644957
TI  - Haemophiliac patient goes to High Court to get synthetic factor VIII.

PMID- 14644959
TI  - Migrants should not be forced to have TB and HIV screening.

PMID- 14644964
TI  - Review of abortion law demanded after abortion for cleft palate.

PMID- 14644966
TI  - Randomised controlled trial of treatment of unilateral visual impairment detected
      at preschool vision screening.
AB  - OBJECTIVES: To test the efficacy of treatment for unilateral visual loss detected
      by preschool vision screening and the extent to which effectiveness varies with
      initial severity. DESIGN: Randomised controlled trial of full treatment with
      glasses and patching, if required, compared with glasses only or no treatment.
      Masked assessment of best corrected acuity after one year of follow up. SETTING:
      Eight UK eye departments. PARTICIPANTS: 177 children aged 3-5 years with mild to
      moderate unilateral impairment of acuity (6/9 to 6/36) detected by screening.
      RESULTS: Children in the full and glasses treatment groups had incrementally
      better visual acuity at follow up than children who received no treatment, but
      the mean treatment effect between full and no treatment was equivalent to only
      one line on a Snellen chart (0.11 log units; 95% confidence interval 0.050 to
      0.171; P < 0.0001). The effects of treatment depended on initial acuity: full
      treatment showed a substantial effect in the moderate acuity group (6/36 to 6/18
      at recruitment) and no significant effect in the mild acuity group (6/9 to 6/12
      at recruitment) (P = 0.006 for linear regression interaction term). For 64
      children with moderate acuity loss the treatment effect was 0.20 log units,
      equivalent to one to two lines on a Snellen chart. When all children had received
      treatment, six months after the end of the trial, there was no significant
      difference in acuity between the groups. CONCLUSIONS: Treatment is worth while in
      children with the poorest acuity, but in children with mild (6/9 to 6/12)
      unilateral acuity loss there was little benefit. Delay in treatment until the age
      of 5 did not seem to influence effectiveness.

PMID- 14644967
TI  - Randomised controlled trial of smoking cessation intervention after admission for
      coronary heart disease.
AB  - OBJECTIVE: To determine whether a nurse led smoking cessation intervention
      affects smoking cessation rates in patients admitted for coronary heart disease.
      DESIGN: Randomised controlled trial. SETTING: Cardiac ward of a general hospital,
      Norway. PARTICIPANTS: 240 smokers aged under 76 years admitted for myocardial
      infarction, unstable angina, or cardiac bypass surgery. 118 were randomly
      assigned to the intervention and 122 to usual care (control group). INTERVENTION:
      The intervention was based on a booklet and focused on fear arousal and
      prevention of relapses. The intervention was delivered by cardiac nurses without
      special training. The intervention was initiated in hospital, and the
      participants were contacted regularly for at least five months. MAIN OUTCOME
      MEASURE: Smoking cessation rates at 12 months determined by self report and
      biochemical verification. RESULTS: 12 months after admission to hospital, 57% (n
      = 57/100) of patients in the intervention group and 37% (n = 44/118) in the
      control group had quit smoking (absolute risk reduction 20%, 95% confidence
      interval 6% to 33%). The number needed to treat to get one additional person who
      would quit was 5 (95% confidence interval, 3 to 16). Assuming all dropouts
      relapsed at 12 months, the smoking cessation rates were 50% in the intervention
      group and 37% in the control group (absolute risk reduction 13%, 0% to 26%).
      CONCLUSION: A smoking cessation programme delivered by cardiac nurses without
      special training, significantly reduced smoking rates in patients 12 months after
      admission to hospital for coronary heart disease.

PMID- 14644968
TI  - Hospital bed utilisation in the NHS, Kaiser Permanente, and the US Medicare
      programme: analysis of routine data.
AB  - OBJECTIVE: To compare the utilisation of hospital beds in the NHS in England,
      Kaiser Permanente in California, and the Medicare programme in the United States
      and California. DESIGN: Analysis of routinely available data from 2000 and 2001
      on inpatient admissions, lengths of stay, and bed days in populations aged over
      65 for 11 leading causes of use of acute beds. SETTING: Comparison of NHS data
      with data from Kaiser Permanente in California and the Medicare programme in
      California and the United States; interviews with Kaiser Permanente staff and
      visits to Kaiser facilities. RESULTS: Bed day use in the NHS for the 11 leading
      causes is three and a half times that of Kaiser's standardised rate, almost twice
      that of the Medicare California's standardised rate, and more than 50% higher
      than the standardised rate in Medicare in the United States. Kaiser achieves
      these results through a combination of low admission rates and relatively short
      stays. The lower use of bed days in Medicare in California compared with Medicare
      in the United States suggests there is a "California effect" as well as a "Kaiser
      effect" in hospital utilisation. CONCLUSION: The NHS can learn from Kaiser's
      integrated approach, the focus on chronic diseases and their effective
      management, the emphasis placed on self care, the role of intermediate care, and
      the leadership provided by doctors in developing and supporting this model of
      care.

PMID- 14644969
TI  - Equity of access to renal transplant waiting list and renal transplantation in
      Scotland: cohort study.
AB  - OBJECTIVE: To examine the access to the renal transplant waiting list and renal
      transplantation in Scotland. DESIGN: Cohort study. SETTING: Renal and transplant
      units in Scotland. PARTICIPANTS: 4523 adults starting renal replacement therapy
      in Scotland between 1 January 1989 and 31 December 1999. MAIN OUTCOME MEASURES:
      Impact of age, sex, social deprivation, primary renal disease, renal or
      transplant unit, and geography on access to the waiting list and renal
      transplantation. RESULTS: 1736 of 4523 (38.4%) patients were placed on the
      waiting list for renal transplantation and 1095 (24.2%) underwent transplantation
      up to 31 December 2000, the end of the study period. Patients were less likely to
      be placed on the list if they were female, older, had diabetes, were in a high
      deprivation category, and were treated in a renal unit in a hospital with no
      transplant unit. Patients living furthest away from the transplant centre were
      listed more quickly. The only factors governing access to transplantation once on
      the list were age, primary renal disease, and year of listing. A significant
      centre effect was found in access to the waiting list and renal transplantation.
      CONCLUSIONS: A major disparity exists in access to the renal transplant waiting
      list and renal transplantation in Scotland. Comorbidity may be an important
      factor.

PMID- 14644970
TI  - Coronary heart disease prevention: insights from modelling incremental cost
      effectiveness.
AB  - OBJECTIVE: To determine which treatments for preventing coronary heart disease
      should be offered to which patients by assessing their incremental cost
      effectiveness. DESIGN: Modelling study. DATA SOURCES: Cost estimates (for NHS)
      and estimates of effectiveness obtained for aspirin, antihypertensive drugs,
      statins and clopidogrel. DATA SYNTHESIS: Treatment effects were assumed to be
      independent, and cost per coronary event prevented was calculated for treatments
      individually and in combination across patients at a range of coronary risks.
      RESULTS: The most cost effective preventive treatments are aspirin, initial
      antihypertensive treatment (bendrofluazide and atenolol), and intensive
      antihypertensive treatment (bendrofluazide, atenolol and enalapril), whereas
      simvastatin and clopidogrel are the least cost effective (cost per coronary event
      prevented in a patient at 10% coronary risk over five years is 3500 pounds
      sterling for aspirin, 12 500 pounds sterling for initial antihypertensives, 18
      300 pounds sterling for intensive antihypertensives, 60 000 pounds sterling for
      clopidogrel, and 61 400 pounds sterling for simvastatin). Aspirin in a patient at
      5% five year coronary risk costs less than a fifth as much per event prevented
      (7900 pounds sterling) as simvastatin in a patient at 30% five year risk (40 800
      pounds sterling). DISCUSSION: A cost effective prevention strategy would offer
      aspirin and initial antihypertensive treatment to all patients at greater than
      7.5% five year coronary risk before offering statins or clopidogrel to patients
      at greater than 15% five year coronary risk. Incremental cost effectiveness
      analysis of treatments produces robust, practical cost effectiveness rankings
      that can be used to inform treatment guidelines.

PMID- 14644971
TI  - Predictive accuracy of the Framingham coronary risk score in British men:
      prospective cohort study.
AB  - OBJECTIVE: To establish the predictive accuracy of the Framingham risk score for
      coronary heart disease in a representative British population. DESIGN:
      Prospective cohort study. SETTING: 24 towns in the United Kingdom. PARTICIPANTS:
      6643 British men aged 40-59 years and free from cardiovascular disease at entry
      into the British regional heart study. MAIN OUTCOME MEASURES: Comparison of
      observed 10 year coronary heart disease mortality and event rates with predicted
      rates for each individual, using the relevant Framingham risk equation. RESULTS:
      Of 6643 men, 2.8% (95% confidence interval 2.4% to 3.2%) died from coronary heart
      disease compared with 4.1% predicted (relative overestimation 47%, P < 0.0001). A
      fatal or non-fatal coronary heart disease event occurred in 10.2% (9.5% to 10.9%)
      of the men compared with 16.0% predicted (relative overestimation 57%, P <
      0.0001). These relative degrees of overestimation were similar at all levels of
      coronary heart disease risk, so that overestimation of absolute risk was greatest
      for those at highest risk. A simple adjustment provided an improved level of
      accuracy. In a "high risk score" approach, most cases occur in the low risk
      group. In this case, 84% of the deaths from coronary heart disease and non-fatal
      events occurred in the 93% of men classified at low risk (< 30% in 10 years) by
      the Framingham score. CONCLUSION: Guidelines for the primary prevention of
      coronary heart disease advocate offering preventive measures to individuals at
      high risk. Currently recommended risk scoring methods derived from the Framingham
      study significantly overestimate the absolute coronary risk assigned to
      individuals in the United Kingdom.

PMID- 14644972
TI  - Lassa fever: epidemiology, clinical features, and social consequences.

PMID- 14644973
TI  - Colchicine in acute gout.

PMID- 14644974
TI  - Resuscitation in pregnancy.

PMID- 14644976
TI  - Using socioeconomic evidence in clinical practice guidelines.

PMID- 14644975
TI  - Ethical problems of evaluating a new treatment for melioidosis.

PMID- 14644977
TI  - Child psychiatric disorder and relative age in school year: holding back may
      cause more harm.

PMID- 14644978
TI  - Child psychiatric disorder and relative age in school year: children need to be
      regarded as individuals in education.

PMID- 14644979
TI  - Child psychiatric disorder and relative age in school year: Holding back may
      cause more harm than good.

PMID- 14644980
TI  - Social anxiety disorder has social and economic burden.

PMID- 14644981
TI  - Role of living liver donation: requirement for transplantation is high.

PMID- 14644982
TI  - Role of living liver donation: surgery violates principles of beneficence and
      autonomy.

PMID- 14644983
TI  - Child psychiatric disorder and relative age in school year: Peer effects need to
      be considered.

PMID- 14644984
TI  - Falls, chronic diseases, and drug use in elderly women: lack of association may
      be explained.

PMID- 14644985
TI  - Morphine for management of refractory dyspnoea: opiates should be used with
      caution.

PMID- 14644987
TI  - Spoofs by any other name.

PMID- 14644988
TI  - Vaseline and burns: vaseline should not be used as first aid for burns.

PMID- 14644989
TI  - A career in oncology.

PMID- 14644991
TI  - Organising a regional teaching programme for the MRCP (UK) examination.

PMID- 14644992
TI  - The benefits of being a general practitioner (for a while).

PMID- 14644993
TI  - The impact of cytomegalovirus serostatus of donor and recipient before
      hematopoietic stem cell transplantation in the era of antiviral prophylaxis and
      preemptive therapy.
AB  - In the current era of effective prophylactic and preemptive therapy,
      cytomegalovirus (CMV) is now a rare cause of early mortality after hematopoietic
      stem cell transplantation (HSCT). However, the ultimate goal of completely
      eliminating the impact of CMV on survival remains elusive. Although the direct
      effects of CMV (ie, CMV pneumonia) have been largely eliminated, several recent
      cohort studies show that CMV-seropositive transplant recipients and seronegative
      recipients of a positive graft appear to have a persistent mortality disadvantage
      when compared with seronegative recipients with a seronegative donor. Recipients
      of T-cell-depleted allografts and/or transplants from unrelated or HLA-mismatched
      donors seem to be predominantly affected. Reasons likely include both incomplete
      prevention of direct and indirect or immunomodulatory effects of CMV as well as
      consequences of drug toxicities. The effect of donor CMV serostatus on outcome
      remains controversial. Large multicenter cohort studies are needed to better
      define the subgroups of seropositive patients that may benefit from intensified
      prevention strategies and to define the impact of CMV donor serostatus in the era
      of high-resolution HLA matching. Prevention strategies may require targeting both
      the direct and indirect effects of CMV infection by immunologic or antiviral drug
      strategies.

PMID- 14644994
TI  - GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of
      multiple myeloma cells in the bone marrow microenvironment.
AB  - Previous studies have shown that the multiple myeloma (MM) cell line and MM
      patient cells express high-affinity vascular endothelial growth factor (VEGF)
      receptor-1 or Fms-like tyrosine kinase-1 (Flt-1) but not VEGF receptor-2 or Flk
      1/kinase insert domain-containing receptor (Flk-1/KDR) and that VEGF triggers MM
      cell proliferation through a mitogen-activated protein kinase (MAPK)-dependent
      pathway and migration through a protein kinase C (PKC)-dependent pathway. The
      present study evaluates the efficacy of the small molecule tyrosine-kinase
      inhibitor GW654652, which inhibits all 3 VEGF receptors with similar potency. We
      show that GW654652 acts directly on MM cells and in the bone marrow
      microenvironment. Specifically, GW654652 (1-10 microg/mL) inhibits, in a dose
      dependent fashion, VEGF-triggered migrational activity and cell proliferation of
      MM cell lines that are sensitive and resistant to conventional therapy. As
      expected from our previous studies of VEGF-induced signaling and sequelae in MM
      cells, GW654652 blocked VEGF-induced Flt-1 phosphorylation and downstream
      activation of AKT-1 and MAPK-signaling cascades. Importantly, GW654652 also
      inhibits interleukin-6 and VEGF secretion and proliferation of MM cells induced
      by tumor cell binding to bone marrow (BM) stromal cells. The activity of a pan
      VEGF receptor inhibitor against MM cells in the BM milieu, coupled with its lack
      of major toxicity in preclinical mouse models, provides the framework for
      clinical trials of this drug class to improve patient outcome in MM.

PMID- 14644995
TI  - Antibody blockade or mutation of the fibrinogen gamma-chain C-terminus is more
      effective in inhibiting murine arterial thrombus formation than complete absence
      of fibrinogen.
AB  - An elevated plasma fibrinogen level is a risk factor for thrombotic
      cardiovascular disease, but which of fibrinogen's functions is responsible for
      the increased risk is unknown. To define better the contribution of fibrinogen to
      large vessel thrombus formation, we studied carotid artery thrombosis in wild
      type mice, mice lacking fibrinogen (fbg-/-), mice treated with 7E9 (a blocking
      antibody to the fibrinogen gamma-chain C-terminus), and mice expressing a mutant
      fibrinogen (gamma delta 5) that lacks the gamma-chain platelet-binding motif
      QADGV. In control mice, thrombus formation resulted in occlusion in 8 +/- 2
      minutes (mean +/- SD). In fbg-/- mice, thrombi grew to large sizes, but then they
      abruptly embolized, confirming previous observations by others in an arteriolar
      thrombus model. In contrast, mice treated with 7E9 and gamma delta 5 mice
      developed only small, nonoclusive mural thrombi and embolization was limited.
      These findings reveal that a fibrinogen antibody, 7E9, or a fibrinogen mutant
      retaining clotting function, can limit thrombus formation more effectively than
      the complete absence of fibrinogen. We hypothesize that the smaller thrombi in
      these animals result from the ability of fibrin to bind and sequester thrombin
      and/or the ability of the altered fibrinogen molecules, which cannot recruit
      platelets, to bind to and passivate the surface.

PMID- 14644996
TI  - Potent inhibition of human platelets by cGMP analogs independent of cGMP
      dependent protein kinase.
AB  - Platelets play a key role in hemostasis through their ability to rapidly adhere
      to activated or injured endothelium, subendothelial matrix proteins, and other
      activated platelets. A strong equilibrium between activating and inhibiting
      processes is essential for normal platelet and vascular function, impairment of
      this equilibrium being associated with either thrombophilic or bleeding
      disorders. Both cyclic guanosine monophosphate (cGMP) and cyclic adenosine
      monophosphate (cAMP) have been established as crucial and synergistic
      intracellular messengers that mediate the effects of platelet inhibitors such as
      nitric oxide (NO) and prostacyclin (PG-I2). However, it was recently suggested
      that a rapid cGMP/cGMP-dependent protein kinase (cGK)-mediated extracellular
      signal-related kinase (ERK) phosphorylation promotes platelet activation. This
      hypothesis was examined here by evaluating established and proposed cGK
      activators/inhibitors with respect to their capacity to promote either platelet
      activation or inhibition. In particular, the regulatory role of cGK for ERK
      phosphorylation and thrombin-, thromboxane-, and VWF-induced platelet activation
      was investigated. The data obtained do not support the concept that cGK-mediated
      ERK phosphorylation promotes platelet activation but confirm the inhibitory role
      of cGK in platelet function. One explanation for these discrepancies is the novel
      finding that extracellular cGMP analogs potently and rapidly inhibit thrombin-,
      thromboxane-, and VWF-induced human platelet signaling and activation by a cGK
      independent mechanism.

PMID- 14644997
TI  - Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis.
AB  - The PTPN11 gene encodes SHP-2 (Src homology 2 domain-containing protein tyrosine
      Phosphatase), a nonreceptor tyrosine protein tyrosine phosphatase (PTPase) that
      relays signals from activated growth factor receptors to p21Ras (Ras) and other
      signaling molecules. Mutations in PTPN11 cause Noonan syndrome (NS), a
      developmental disorder characterized by cardiac and skeletal defects. NS is also
      associated with a spectrum of hematologic disorders, including juvenile
      myelomonocytic leukemia (JMML). To test the hypothesis that PTPN11 mutations
      might contribute to myeloid leukemogenesis, we screened the entire coding region
      for mutations in 51 JMML specimens and in selected exons from 60 patients with
      other myeloid malignancies. Missense mutations in PTPN11 were detected in 16 of
      49 JMML specimens from patients without NS, but they were less common in other
      myeloid malignancies. RAS, NF1, and PTPN11 mutations are largely mutually
      exclusive in JMML, which suggests that mutant SHP-2 proteins deregulate myeloid
      growth through Ras. However, although Ba/F3 cells engineered to express leukemia
      associated SHP-2 proteins cells showed enhanced growth factor-independent
      survival, biochemical analysis failed to demonstrate hyperactivation of the Ras
      effectors extracellular-regulated kinase (ERK) or Akt. We conclude that SHP-2 is
      an important cellular PTPase that is mutated in myeloid malignancies. Further
      investigation is required to clarify how these mutant proteins interact with Ras
      and other effectors to deregulate myeloid growth.

PMID- 14644998
TI  - Multiparameter analysis of murine bone marrow side population cells.
AB  - We describe the multiparameter flow cytometric analysis of the relationship
      between side population (SP) formation and well-characterized, antigen-defined
      stem cell subsets. We also compared the competitive repopulation ability of
      subsets defined by the SP profile to those identified by antigenic markers. The
      vast majority of SP cells possessed a primitive cell phenotype (c-kit+, SCA-1+,
      Thy-1+, CD31+, CD135neg, lineage neg), but only a minority of antigen-defined
      subsets were SP cells. Hence, although SP cells are identified independently of
      antigenic markers, they are not distinct from established stem cell phenotypes,
      but are a small subset of them. Approximately half of SP cells expressed CD34 at
      readily detectable levels, and one-third of SP cells possessed the primitive c
      kit+, SCA-1+, lineage neg, CD34neg cell phenotype. Since most SP cells are a
      subset of c-kit+, Thy-1+, lineage neg, SCA-1+ cells (KTLS), we determined whether
      the SP cell subset represents a further enrichment in long-term repopulating cell
      content. The SP+ subset of KTLS+ cells was more enriched for competitive
      repopulation units than the SP- fraction of KTLS+ cells. Hence, the SP cell
      fraction highlights a subset of the long-term repopulating cells found within the
      already highly purified KTLS fraction.

PMID- 14644999
TI  - CD200 is a novel p53-target gene involved in apoptosis-associated immune
      tolerance.
AB  - During apoptotic cell death, biochemical processes modify self-proteins and
      create potential autoantigens. To maintain self-tolerance in the face of natural
      cell turnover, the immune system must prevent or control responses to apoptosis
      associated autoantigens or risk autoimmunity. The molecular mechanisms governing
      this process remain largely unknown. Here, we show that expression of the
      immunoregulatory protein CD200 increases as murine dendritic cells (DCs) undergo
      apoptosis. We define CD200 as a p53-target gene and identify both p53- and
      caspase-dependent pathways that control CD200 expression during apoptosis. CD200
      expression on apoptotic DCs diminishes proinflammatory cytokine production in
      response to self-antigens in vitro and is required for UVB-mediated tolerance to
      haptenated self-proteins in vivo. Up-regulation of CD200 may represent a novel
      mechanism, whereby immune reactivity to apoptosis-associated self-antigens is
      suppressed under steady state conditions.

PMID- 14645000
TI  - Correction of hypercoagulability and amelioration of pulmonary arterial
      hypertension by chronic blood transfusion in an asplenic hemoglobin E/beta
      thalassemia patient.
AB  - Chronic transfusion of packed red blood cells, in addition to other ongoing
      treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other
      supportive measures, was given to a splenectomized hemoglobin E/beta-thalassemia
      woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma
      thrombin-antithrombin III complex (TAT) levels and right-sided cardiac
      catheterization were used to monitor changes after treatment. Reduction of plasma
      TAT levels from 7.5 to 3.8 microg/L (normal, 3 +/- 2.4 microg/L), pulmonary
      vascular resistance (PVR) from 553.8 to 238.6 dyne.sec.cm(-5) (normal, 67 +/- 30
      dyne.sec.cm(-5)), and mean pulmonary arterial pressure from 51 to 32 mm Hg
      (normal, 9 to 19 mm Hg) occurred in tandem. Normalization of blood
      hypercoagulability as reflected in plasma TAT level by chronic blood transfusion
      was the likely basis for improvement of increased PVR, being secondary to
      thrombotic pulmonary arteriopathy and subsequently PHT.

PMID- 14645001
TI  - Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a
      retrospective multicentric clinical study.
AB  - To assess the prognosis of peripheral T-cell lymphoma unspecified, we
      retrospectively analyzed 385 cases fulfilling the criteria defined by the World
      Health Organization classification. Factors associated with a worse overall
      survival (OS) in a univariate analysis were age older than 60 years (P=.0002),
      equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH)
      value at normal levels or above (P<.0001), performance status (PS) equal to or
      more than 2 (P< or =.0001), stage III or higher (P=.0001), and bone marrow
      involvement (P=.0001). Multivariate analysis showed that age (relative risk,
      1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269
      2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001),
      and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026)
      were factors independently predictive for survival. Using these 4 variables we
      constructed a new prognostic model that singled out 4 groups at different risk:
      group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%,
      respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and
      38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and
      18.0%, respectively; group 4, 3 or 4 factors, with a 5-year and 10-year OS of
      18.3 and 12.6%, respectively (P< or =.0001; log-rank, 66.79).

PMID- 14645002
TI  - A novel mechanism of complement-independent clearance of red cells deficient in
      glycosyl phosphatidylinositol-linked proteins.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia
      characterized by the increased sensitivity of red blood cells (RBCs) to
      complement, leading to intravascular hemolysis and hemoglobinuria. PNH is due to
      the expansion of a cell clone that has acquired a mutation in the PIGA gene. Mice
      with targeted Piga gene inactivation genetically mimic the human disease and have
      phosphatidylinositol glycan class A-negative (PIGA-) RBCs with a reduced half
      life in circulation. Although PIGA-RBCs are hypersensitive to complement in
      vitro, their complement sensitivity in vivo is barely detectable. Here we show
      that the shortened survival of PIGA- RBCs is independent of complement either by
      using inhibitory C5 antibodies or by transfusion into C5-, C4-, C3-, or factor B
      deficient mice. Splenectomy or high-dose cortisone treatment had no effect on the
      shorter survival of PIGA- RBCs. However, treatment with liposome-encapsulated
      clodronate, an agent that depletes macrophages in vivo, normalized the half-life
      of PIGA- RBCs. This indicates that the shortened survival of PIGA- RBCs is due to
      a novel pathway of PIGA- RBC clearance that is mediated by macrophages, but
      occurs independently of complement. Future investigations will show whether this
      novel pathway of PIGA- RBC destruction identified in mice may also operate in
      patients with PNH.

PMID- 14645003
TI  - Interruption of the NF-kappaB pathway by Bay 11-7082 promotes UCN-01-mediated
      mitochondrial dysfunction and apoptosis in human multiple myeloma cells.
AB  - Interactions between pharmacologic NF-kappaB inhibitors (eg, Bay 11-7082, SN-50)
      and the checkpoint abrogator UCN-01 have been examined in human multiple myeloma
      (MM) cells. Exposure of U266 cells to Bay 11-7082 (Bay) in combination with UCN
      01 resulted in the abrogation of NF-kappaB/DNA binding activity and the
      synergistic induction of apoptosis. Comparable synergism was observed in other MM
      cell lines and patient-derived CD138+ cells and between an inhibitory peptide of
      NF-kappaB (SN50) and UCN-01. Bay/UCN-01-mediated lethality involved mitochondrial
      dysfunction, caspase cleavage, and poly adenosine diphosphate-ribose polymerase
      (PARP) degradation. Although Bay modestly blocked UCN-01-induced extracellular
      signal-regulated kinase (ERK) phosphorylation, coadministration activated c-Jun N
      terminal kinase (JNK) and cdc2/cdk1 and down-regulated Mcl-1, XIAP, and Bcl-xL.
      Transfection with a constitutively activated mitogen-activated protein kinase
      kinase (MEK1)/green fluorescent protein (GFP) construct failed to block apoptosis
      induced by Bay/UCN-01 but significantly attenuated MEK inhibitor (U0126)/UCN-01
      induced lethality. Inhibiting JNK activation with SP600125 or D-JNKI1 peptide
      markedly reduced Bay/UCN-01-mediated mitochondrial dysfunction and apoptosis and
      the down-regulation of Mcl-1, XIAP, and Bcl-xL but not of cdc2/cdk1 activation.
      Stable transfection of cells with dominant-negative caspase-9 dramatically
      diminished Bay/UCN-01 lethality without altering JNK or cdc2/cdk1 activation.
      Neither interleukin-6 (IL-6)- nor fibronectin-mediated adherence conferred
      resistance to Bay/UCN-01-induced apoptosis. Together, these findings suggest that
      a strategy combining UCN-01 with disruption of the IkappaB kinase
      (IKK)/IkappaB/NF-kappaB pathway warrants attention in MM.

PMID- 14645004
TI  - Mast cell-mediated inflammatory responses require the alpha 2 beta 1 integrin.
AB  - Although the alpha 2 beta 1 integrin is widely expressed and has been extensively
      studied, it has not been previously implicated in mast cell biology. We observed
      that alpha 2 integrin subunit-deficient mice exhibited markedly diminished
      neutrophil and interleukin-6 responses during Listeria monocytogenes- and zymosan
      induced peritonitis. Since exudative neutrophils of wild-type mice expressed
      little alpha 2 beta 1 integrin, it seemed unlikely that this integrin mediated
      neutrophil migration directly. Here, we demonstrate constitutive alpha 2 beta 1
      integrin expression on peritoneal mast cells. Although alpha 2-null mice contain
      normal numbers of peritoneal mast cells, these alpha 2-null cells do not support
      in vivo mast cell-dependent inflammatory responses. We conclude that alpha 2 beta
      1 integrin provides a costimulatory function required for mast cell activation
      and cytokine production in response to infection.

PMID- 14645006
TI  - Identification of circulating antigen-specific CD4+ T lymphocytes with a CCR5+,
      cytotoxic phenotype in an HIV-1 long-term nonprogressor and in CMV infection.
AB  - Antigen-specific CD4+ effector T cells primarily provide help for B-cell antibody
      responses and CD8+ cytotoxic T-lymphocyte (CTL) responses. We have found an
      expanded population of HIV-1 p24-specific, T-cell receptor V beta 17+, CD4+ T
      lymphocytes, defined by in vitro proliferative and interferon-gamma responses to
      a 15-mer Gag peptide, in the peripheral blood of an individual with long-term
      nonprogressive HIV-1 infection. Ex vivo, these cells were CCR5+ and CCR7-,
      consistent with an effector/memory function. Surprisingly, these cells highly
      expressed several proteins characteristic of cytotoxic lymphocytes, including TIA
      1 (T-cell intracellular antigen 1; GMP-17/NKG7), granzymes A and B, CD161 (NKRP
      1), and CD244 (C1.7/2B4). Following in vitro peptide stimulation, these cells
      produced interleukin 2 (IL-2) and intracellular CD40L, suggesting possible helper
      function, in addition to induction of perforin and cytotoxicity. A subset of
      cytomegalovirus (CMV)-specific CD4+ T cells in healthy adults similarly expressed
      these CTL markers and CCR5, ex vivo. Furthermore, this distinct subset of CD4+ T
      cells was significantly elevated in healthy CMV-seropositive adults, compared
      with CMV-seronegative individuals. These results suggest that CCR5+ CD4+ CTL may
      be a major effector mechanism of the immune response to viral infections in
      humans. Moreover, expression of CCR5 may render them particularly susceptible to
      cytopathic effects during progressive HIV-1 infection.

PMID- 14645007
TI  - Homer-3 regulates activation of serum response element in T cells via its EVH1
      domain.
AB  - Drosophila enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1
      (EVH1) domain proteins regulate signal transduction at the neuronal and
      immunologic synapse. Despite shared cell biologic machinery at these synapses,
      the regulation of client proteins that transmit synaptic activity to the nucleus
      is likely to be different. Homer-3, a member of the EVH1 family, is expressed in
      the thymus, suggesting a role for this protein in T-cell signal transduction.
      Upon T-cell receptor (TCR) engagement, Homer-3 was recruited to the contact area
      of Jurkat cells to anti-CD3 and CD28 antibody-coated beads prior to actin
      accumulation and was subsequently translocated into the nucleus. Overexpression
      of Homer-3 reduced transcriptional activation via the serum response element
      (SRE) in response to anti-CD3 antibody, phorbol ester, or dominant active Ha-Ras.
      Consistent with these results, knockdown of Homer-3 increased SRE activation.
      Homer-3 coprecipitated with CCAAT/enhancer binding protein beta (C/EBP beta), one
      of the transcription factors that binds to the SRE and has a consensus motif
      binding to EVH1 domain. Moreover, Homer-3 and its EVH1 domain fragment reduced
      transcriptional activation of C/EBP beta. These findings suggest that Homer-3 may
      be involved in the regulation of SRE activation in T cells via interaction
      between its EVH1 domain and C/EBP beta.

PMID- 14645008
TI  - Defective B-cell-negative selection and terminal differentiation in the ICF
      syndrome.
AB  - Immunodeficiency, centromeric region instability, and facial anomalies (ICF)
      syndrome is a rare autosomal recessive disease. Mutations in the DNA
      methyltransferase 3B (DNMT3B) gene are responsible for most ICF cases reported.
      We investigated the B-cell defects associated with agammaglobulinemia in this
      syndrome by analyzing primary B cells from 4 ICF patients. ICF peripheral blood
      (PB) contains only naive B cells; memory and gut plasma cells are absent. Naive
      ICF B cells bear potentially autoreactive long heavy chain variable regions
      complementarity determining region 3's (V(H)CDR3's) enriched with positively
      charged residues, in contrast to normal PB transitional and mature B cells,
      indicating that negative selection is impaired in patients. Like anergic B cells
      in transgenic models, newly generated and immature B cells accumulate in PB.
      Moreover, these cells secrete immunoglobulins and exhibit increased apoptosis
      following in vitro activation. However, they are able to up-regulate CD86,
      indicating that mechanisms other than anergy participate in silencing of ICF B
      cells. One patient without DNMT3B mutations shows differences in immunoglobulin E
      (IgE) switch induction, suggesting that immunodeficiency could vary with the
      genetic origin of the syndrome. In this study, we determined that negative
      selection breakdown and peripheral B-cell maturation blockage contribute to
      agammaglobulinemia in the ICF syndrome.

PMID- 14645009
TI  - Molecular response to imatinib in late chronic-phase chronic myeloid leukemia.
AB  - Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces
      cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these
      patients measuring response by molecular techniques is clearly required. We
      determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191
      patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously
      treated with interferon alpha. MR was assessed with real-time quantitative
      (TaqMan) reverse transcription-polymerase chain reaction and was expressed as the
      ratio between BCR/ABL and beta 2-microglobulin x 100, the lowest level of
      detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in
      85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85
      patients. A reduction of the transcript level of more than 2 logs was achieved in
      all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the
      median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months,
      with the transcript level undetectable in 22 cases. We conclude that in CCgRs the
      degree of MR may vary from 2 to more than 4 logs, and that there is a progressive
      decrease of transcript level by time. Only 1 of 22 negative cases has had a
      relapse as yet.

PMID- 14645010
TI  - Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2
      and phosphorylation of RGS proteins.
AB  - We have applied a proteomics approach to analyze signaling cascades in human
      platelets stimulated by thrombin receptor activating peptide (TRAP). By analyzing
      basal and TRAP-activated platelets using 2-dimensional gel electrophoresis (2
      DE), we detected 62 differentially regulated protein features. From these, 41
      could be identified by liquid chromatography-coupled tandem mass spectrometry (LC
      MS/MS) and were found to derive from 31 different genes, 8 of which had not
      previously been reported in platelets, including the adapter downstream of
      tyrosine kinase 2 (Dok-2). Further studies revealed that the change in mobility
      of Dok-2 was brought about by tyrosine phosphorylation. Dok-2 tyrosine
      phosphorylation was also found to be involved in collagen receptor, glycoprotein
      VI (GPVI), signaling as well as in outside-in signaling through the major
      platelet integrin, alpha IIIb beta 3. These studies also provided the first
      demonstration of posttranslational modification of 2 regulator of G protein
      signaling (RGS) proteins, RGS10 and 18. Phosphorylation of RGS18 was mapped to
      Ser49 by MS/MS analysis. This study provides a new approach for the
      identification of novel signaling molecules in activated platelets, providing new
      insights into the mechanisms of platelet activation and building the basis for
      the development of therapeutic agents for thrombotic diseases.

PMID- 14645011
TI  - Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg
      cells in Hodgkin lymphomas.
AB  - p18INK4c is a cyclin-dependent kinase (CDK) inhibitor that interferes with the Rb
      kinase activity of CDK6/CDK4. Disruption of p18INK4c in mice impairs B-cell
      terminal differentiation and confers increased susceptibility to tumor
      development; however, alterations of p18INK4c in human tumors have rarely been
      described. We used a tissue-microarray approach to analyze p18INK4c expression in
      316 Hodgkin lymphomas (HLs). Nearly half of the HL cases showed absence of
      p18INK4c protein expression by Reed-Sternberg (RS) cells, in contrast with the
      regular expression of p18INK4c in normal germinal center cells. To investigate
      the cause of p18INK4c repression in RS cells, the methylation status of the
      p18INK4c promoter was analyzed by methylation-specific polymerase chain reaction
      (PCR) and bisulfite sequencing. Hypermethylation of the p18INK4c promoter was
      detected in 2 of 4 HL-derived cell lines, but in none of 7 non-Hodgkin lymphoma
      (NHL)-derived cell lines. We also detected p18INK4c hypermethylation, associated
      with absence of protein expression, in 5 of 26 HL tumors. The correlation of
      p18INK4c immunostaining with the follow-up of the patients showed shorter overall
      survival in negative cases, independent of the International Prognostic Score.
      These findings suggest that p18INK4c may function as a tumor suppressor gene in
      HL, and its inactivation may contribute to the cell cycle deregulation and
      defective terminal differentiation characteristic of the RS cells.

PMID- 14645012
TI  - A novel mechanism for imatinib mesylate-induced cell death of BCR-ABL-positive
      human leukemic cells: caspase-independent, necrosis-like programmed cell death
      mediated by serine protease activity.
AB  - Caspase-independent programmed cell death can exhibit either an apoptosis-like or
      a necrosis-like morphology. The ABL kinase inhibitor, imatinib mesylate, has been
      reported to induce apoptosis of BCR-ABL-positive cells in a caspase-dependent
      fashion. We investigated whether caspases alone were the mediators of imatinib
      mesylate-induced cell death. In contrast to previous reports, we found that a
      broad caspase inhibitor, zVAD-fmk, failed to prevent the death of imatinib
      mesylate-treated BCR-ABL-positive human leukemic cells. Moreover, zVAD-fmk
      preincubated, imatinib mesylate-treated cells exhibited a necrosis-like
      morphology characterized by cellular pyknosis, cytoplasmic vacuolization, and the
      absence of nuclear signs of apoptosis. These cells manifested a loss of the
      mitochondrial transmembrane potential, indicating the mitochondrial involvement
      in this caspase-independent necrosis. We excluded the participation of several
      mitochondrial factors possibly involved in caspase-independent cell death such as
      apoptosis-inducing factor, endonuclease G, and reactive oxygen species. However,
      we observed the mitochondrial release of the serine protease Omi/HtrA2 into the
      cytosol of the cells treated with imatinib mesylate or zVAD-fmk plus imatinib
      mesylate. Furthermore, serine protease inhibitors prevented the caspase
      independent necrosis. Taken together, our results suggest that imatinib mesylate
      induces a caspase-independent, necrosis-like programmed cell death mediated by
      the serine protease activity of Omi/HtrA2.

PMID- 14645013
TI  - Initial accumulation of platelets during arterial thrombus formation in vivo is
      inhibited by elevation of basal cAMP levels.
AB  - Platelet accumulation at sites of vascular injury is the primary event in
      arterial thrombosis. Initial platelet accrual into thrombi is mediated by
      interactions of platelet adhesion receptors with ligands on the injured
      endothelium or in the sub-endothelial matrix. The role of intracellular signals
      in initial platelet accumulation at sites of endothelial injury, however, is the
      subject of debate. We have used a newly discovered inhibitor of phosphodiesterase
      3A (PDE3A) and the well-characterized PDE3A inhibitor, cilostazol, to modulate
      3',5'-cyclic adenosine monophosphate (cAMP) levels in an in vivo model that
      enables the kinetic analysis of platelet accumulation. These studies demonstrate
      that elevation of basal cAMP levels results in an overall decline in platelet
      accumulation at the site of vascular injury. In particular, the initial rate of
      accumulation of platelets is inhibited by elevation of cAMP. Analysis of the
      kinetics of individual platelets at injury sites using intravital microscopy
      demonstrates that cAMP directs the rate at which platelets attach to and detach
      from thrombi. These studies demonstrate that cAMP in circulating platelets
      controls attachment to and detachment from sites of arteriolar injury. Thus, the
      status of the intracellular signaling machinery prior to engagement of platelet
      receptors influences the rate of platelet accumulation during thrombus formation.

PMID- 14645014
TI  - The plaque lipid lysophosphatidic acid stimulates platelet activation and
      platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and
      P2Y12 receptors.
AB  - Despite the fact that lysophosphatidic acid (LPA) has been identified as a main
      platelet-activating lipid of mildly oxidized low-density lipoprotein (LDL) and
      human atherosclerotic lesions, it remains unknown whether it is capable of
      activating platelets in blood. We found that LPA at concentrations slightly above
      plasma levels induces platelet shape change, aggregation, and platelet-monocyte
      aggregate formation in blood. 1-alkyl-LPA (16:0 fatty acid) was almost 20-fold
      more potent than 1-acyl-LPA (16:0). LPA directly induced platelet shape change in
      blood and platelet-rich plasma obtained from all blood donors. However, LPA
      stimulated platelet aggregation in blood was donor dependent. It could be
      completely blocked by apyrase and antagonists of the platelet adenosine
      diphosphate (ADP) receptors P2Y1 and P2Y12. These substances also inhibited LPA
      induced aggregation of platelet-rich plasma and aggregation and serotonin
      secretion of washed platelets. These results indicate a central role for ADP
      mediated P2Y1 and P2Y12 receptor activation in supporting LPA-induced platelet
      aggregation. Platelet aggregation and platelet-monocyte aggregate formation
      stimulated by LPA was insensitive to inhibition by aspirin. We conclude that LPA
      at concentrations approaching those found in vivo can induce platelet shape
      change, aggregation, and platelet-monocyte aggregate formation in whole blood and
      suggest that antagonists of platelet P2Y1 and P2Y12 receptors might be useful
      preventing LPA-elicited thrombus formation in patients with cardiovascular
      diseases.

PMID- 14645015
TI  - Hidden costs of mental illness.

PMID- 14645016
TI  - The future of in-patient child and adolescent mental health services.

PMID- 14645017
TI  - Functional MRI and parental responsiveness: a new avenue into parental
      psychopathology and early parent-child interactions?

PMID- 14645018
TI  - Treating psychological symptoms in sexually abused children: from research
      findings to service provision.
AB  - BACKGROUND: The experience of having been sexually abused is associated with a
      wide range of psychiatric symptoms and difficulties, and these problems can
      persist over years. The psychological treatment of children who have experienced
      sexual abuse has only recently begun to be systematically investigated. An
      increasing number of robust studies have been conducted. AIMS: To review
      systematically the available evidence from randomised controlled trials of
      psychological treatments for children who have been sexually abused, and to
      consider the place of these treatments in a multi-disciplinary service. METHOD: A
      systematic search of the available research was undertaken. Included trials were
      critically appraised and the results considered. RESULTS: Twelve studies were
      included in the review. The best evidence of efficacy for improving psychological
      symptoms in these children was found for cognitive-behavioural therapy,
      particularly for young children. CONCLUSIONS: Efficacious treatments existto
      improve psychological symptoms in children who have experienced sexual abuse.
      Consideration is given to the place of these treatments within the response of a
      multi-disciplinary service.

PMID- 14645019
TI  - Biochemical terrorism: too awful to contemplate, too serious to ignore:
      subjective literature review.
AB  - BACKGROUND: It is important not to foster unnecessary public anxiety with regard
      to the risk of a biochemical terrorist incident, but the authorities need to
      consider their response strategy, particularly with regard to mental health
      issues. AIMS: To describe the likely effects of a terrorist incident involving
      biochemical agents and to identify important response issues. METHOD: Literature
      survey. RESULTS: Observations following conventional terrorist incidents and
      other major trauma, including biochemical and nuclear accidents, suggest that a
      biochemical terrorist incident would have widespread public effects. The mental
      health services should play a major role in designing an effective multi
      disciplinary response, particularly with regard to the reduction of public
      anxiety, identifying at-risk individuals and collaborating with medical and
      emergency services, as well as providing care for those who develop post
      traumatic psychopathology. CONCLUSIONS: We should not feel helpless in the face
      of a biochemical threat; there is considerable knowledge and experience to be
      tapped. A well-designed, well-coordinated and rehearsed strategy based on
      empirical evidence will do much to reduce public anxiety and increase
      professional confidence.

PMID- 14645020
TI  - Quantitative analysis of sponsorship bias in economic studies of antidepressants.
AB  - BACKGROUND: Concern is widespread about potential sponsorship influence on
      research, especially in pharmacoeconomic studies. Quantitative analysis of
      possible bias in such studies is limited. AIMS: To determine whether there is an
      association between sponsorship and quantitative outcomes in pharmacoeconomic
      studies of antidepressants. METHOD: Using all identifiable articles with original
      comparative quantitative cost or cost-effectiveness outcomes for antidepressants,
      we performed contingency table analyses of study sponsorship and design v. study
      outcome. RESULTS: Studies sponsored by selective serotonin reuptake inhibitor
      (SSRI) manufacturers favoured SSRIs over tricyclic antidepressants more than non
      industry-sponsored studies. Studies sponsored by manufacturers of newer
      antidepressants favoured these drugs more than did non-industry-sponsored
      studies. Among industry-sponsored studies, modelling studies favoured the
      sponsor's drug more than did administrative studies. Industry-sponsored modelling
      studies were more favourable to industry than were non-industry-sponsored ones.
      CONCLUSIONS: Pharmacoeconomic studies of antidepressants reveal clear
      associations of study sponsorship with quantitative outcome.

PMID- 14645021
TI  - Pattern of antidepressant use and duration of depression-related absence from
      work.
AB  - BACKGROUND: Few studies have examined the relationship between antidepressant
      prescription and receipt of depression-related disability benefits. AIMS: To
      address two questions: first, is prescription of antidepressants in accordance
      with published clinical guides associated with better disability outcomes, and
      second, what is the relationship between guideline-concordant antidepressant
      prescription and length of disability? METHOD: An observational study was
      conducted using administrative data from three major Canadian financial and
      insurance sector companies. Short-term disability and prescription drug claims
      records for 1996-1998 were linked for workers receiving depression-related short
      term disability benefits during that time. RESULTS: Recommended first-line agents
      and recommended doses were significantly associated with return to work
      (chi(2)=6.64, P<0.036). In addition, among those who returned to work, early
      intervention was significantly associated with a shortened disability episode
      (beta=-24.1; 95% CI -34.4 to -13.8). CONCLUSIONS: Depression-related workplace
      disability is a problem for which there is no simple solution. These results
      provide an additional piece to the puzzle of helping workers disabled by
      depression to return to work.

PMID- 14645022
TI  - Cost of depression among adults in England in 2000.
AB  - BACKGROUND: The cost of depression in the UK was estimated at pound 3.5 billion
      almost a decade ago. The shift to community-based management for depression
      alongside the availability of more accurate data have allowed these estimates to
      be revised. AIMS: To calculate the total cost of depression in adults in England
      during 2000. METHOD: Recorded data on health service use by patients with
      depression were analysed and the cost of treating patients was calculated. The
      cost of working life lost was estimated from sickness benefit claims and the
      number of registered deaths of patients with depression. RESULTS: The total cost
      of adult depression was estimated at over pound 9 billion, of which pound 370
      million represents direct treatment costs. There were 109.7 million working days
      lost and 2615 deaths due to depression in 2000. CONCLUSIONS: Despite awareness
      campaigns and the availability of effective treatments, depression remains a
      considerable burden on both society and the individual, especially in terms of
      incapacity to work.

PMID- 14645023
TI  - Childhood origins of violent behaviour in adults with schizophreniform disorder.
AB  - BACKGROUND: People with psychosis have an elevated risk of violence. AIMS: To
      examine whether violent behaviour in adults with psychosis can be accounted for
      by psychotic symptoms or physical aggression in childhood. METHOD: We used data
      from a prospective longitudinal study of a complete birth cohort born in New
      Zealand. When cohort members were 26 years old, information was obtained on past
      year psychiatric diagnosis of schizophreniform disorder and on violent behaviour.
      Childhood psychotic symptoms were measured at age 11 years using a diagnostic
      interview, and childhood physical aggression was assessed by teachers when cohort
      members were aged 7, 9 and 11 years. RESULTS: Participants with schizophreniform
      disorder were more likely to be violent than participants without, even after
      controlling for sociodemographic variables and concurrent substance dependence
      disorders. Childhood psychotic symptoms were a strong risk factor for violence in
      adults with schizophreniform disorder, as was childhood physical aggression,
      although to a lesser extent. CONCLUSIONS: Violence by individuals with
      schizophreniform disorder could be prevented by monitoring early signs of
      psychotic symptoms and by controlling childhood physical aggression.

PMID- 14645024
TI  - Prevalence and experience of harassment of people with mental health problems
      living in the community.
AB  - BACKGROUND: The levels and experiences of harassment of people with mental health
      problems in the community compared with those of the general population have not
      been explored. AIMS: To measure the levels and experience of harassment
      experienced by people with mental health problems in the community in Scotland
      and compare them with the general population. METHOD: Experiences of harassment
      were collected by interviewing 165 individuals with mental health problems and a
      control group of 165 people from the general population. RESULTS: Harassment in
      the community was found to be twice as common for individuals with mental health
      problems (41%) than for those in the general population (15%). The harassment
      commonly involved verbal abuse referring to the individual's mental health
      problems and was committed primarily by teenagers and neighbours. CONCLUSIONS:
      Harassment has a significantly higher prevalence among individuals with mental
      health problems living in the community and is believed to have a detrimental
      effect on mental health.

PMID- 14645025
TI  - Diet, smoking and cardiovascular risk in people with schizophrenia: descriptive
      study.
AB  - BACKGROUND: Physical health of people with schizophrenia is poor and they die
      early from cardiovascular disease. AIMS: To describe the lifestyle of people with
      schizophrenia through diet, smoking habits, weight and exercise, and to report
      risk of coronary heart disease (CHD). METHOD: Dietary habits of 102 community
      dwelling people with schizophrenia were assessed by the Scottish Health Survey
      Questionnaire. Also assessed were smoking habits, physical activity, biochemical
      indices of nutrition and future risk of CHD. RESULTS: Fewer males, compared with
      the general population, reached acceptable levels for consumption of fruit,
      vegetables, milk, potatoes and pulses. Fewer females reached the levels for
      consumption of milk and potatoes. Mean number of fruit and vegetable portions
      consumed per week was 16 (s.d.=14); 71 (70%) were smokers; 25 (86%) females and
      50 (70%) males were over weight or obese; 59 (59%) considered themselves
      physically active; 46 (53%) had a raised cholesterol: high-density lipoprotein
      ratio, and 64 (74%) a low alpha-tocopherol: cholesterol ratio. Mean 10-year risk
      of CHD in males was 10.5% (s.d.=8) and in females 7% (s.d.=6). CONCLUSIONS: The
      lifestyle of people with schizophrenia must give cause for concern in relation to
      CHD. Care from concern in relation to secondary care services must address
      physical as well as mental health.

PMID- 14645026
TI  - Mental health services for war-affected children: report of a survey in Kosovo.
AB  - BACKGROUND: In war-affected societies it is assumed that the major mental health
      problem facing the population will be stress reactions. AIMS: To describe the
      creation of a child and adolescent mental health service (CAMHS) in Kosovo after
      the military conflict ended in 1999, and to establish the range of problems and
      diagnoses that presented. METHOD: Data were collected on 559 patients over 2
      years, including their referring problems and diagnoses. RESULTS: Stress-related
      disorders constituted only a fifth of the case-load in year 1. A substantial
      number of patients were symptom-free but attended because they had been exposed
      to a traumatic event, and believed it might make them ill. Non-organic enuresis
      and learning disability were the most common diagnoses in year 2. Many patients
      had a complex mix of social and psychological difficulties that did not fit
      conventional diagnostic categories. CONCLUSIONS: Mental health services that only
      address traumatic stress may fail to meet the needs of war-affected children. A
      comprehensive, culturally appropriate CAMHS is needed to address a wide range of
      problems including learning disability. It should be developed through local
      actors, and build on existing local infrastructure. Services can also have an
      educational role in 'depathologising' normative responses.

PMID- 14645027
TI  - Distribution and characteristics of in-patient child and adolescent mental health
      services in England and Wales.
AB  - BACKGROUND: Little is known about the current state of provision of child and
      adolescent mental health service in-patient units in the UK. AIMS: To describe
      the full number, distribution and key characteristics of child and adolescent
      psychiatric in-patient units in England and Wales. METHOD: Following
      identification of units, data were collected by a postal general survey with
      telephone follow-up. RESULTS: Eighty units were identified; these provided 900
      beds, of which 244 (27%) were managed by the independent sector. Units are
      unevenly distributed, with a concentration of beds in London and the south-east
      of England. The independent sector, which manages a high proportion of specialist
      services and eating disorder units in particular, accentuates this uneven
      distribution. Nearly two-thirds of units reported that they would not accept
      emergency admissions. CONCLUSIONS: A national approach is needed to the planning
      and commissioning of this specialist service.

PMID- 14645028
TI  - Mental health and quality of life of gay men and lesbians in England and Wales:
      controlled, cross-sectional study.
AB  - BACKGROUND: Little is known about the mental health of gay men and lesbians
      living in Europe. AIMS: To compare psychological status, quality of life and use
      of mental health services by lesbians and gay men with heterosexual people.
      METHOD: Cross-sectional study in England and Wales using 'snowball' sampling.
      RESULTS:  PARTICIPANTS: 656 gay men, 505 heterosexual men, 430 lesbians and 588
      heterosexual women. Gay men were more likely than heterosexual men to score above
      threshold on the Clinical Interview Schedule, indicating greater levels of
      psychological distress (RR 1.24, 95% CI 1.07-1.43), as were lesbians compared
      with heterosexual women (RR 1.30, 95% CI 1.11-1.52). Gay men and lesbians were
      more likely than heterosexuals to have consulted a mental health professional in
      the past, deliberately harmed themselves and used recreational drugs. Lesbians
      were more likely to have experienced verbal and physical intimidation and to
      consume more alcohol than heterosexual women. CONCLUSIONS: Awareness of mental
      health issues for gay men and lesbians should become a standard part of training
      for mental health professionals, who need to be aware of the potential for
      substance misuse and self-harm in this group and of the discrimination
      experienced by many lesbians.

PMID- 14645029
TI  - Psychosis research at Maastricht University, The Netherlands.

PMID- 14645030
TI  - Suicide and self-harm.

PMID- 14645031
TI  - The endeavour to become international.

PMID- 14645032
TI  - Psychiatric services for ethnic minority groups: a third way?

PMID- 14645033
TI  - What is early intervention?

PMID- 14645034
TI  - Neuroimaging psychopathy: lessons from Lombroso.

PMID- 14645035
TI  - Scientific psychiatry?

PMID- 14645037
TI  - State and spectral properties of chloride oscillations in pollen.

PMID- 14645038
TI  - Why can't protons move through water channels?

PMID- 14645039
TI  - New angles for NMR studies of biological molecules.

PMID- 14645040
TI  - Interactions of hydrophobic peptides with lipid bilayers: Monte Carlo simulations
      with M2delta.
AB  - We introduce here a novel Monte Carlo simulation method for studying the
      interactions of hydrophobic peptides with lipid membranes. Each of the peptide's
      amino acids is represented as two interaction sites: one corresponding to the
      backbone alpha-carbon and the other to the side chain, with the membrane
      represented as a hydrophobic profile. Peptide conformations and locations in the
      membrane and changes in the membrane width are sampled using the Metropolis
      criterion, taking into account the underlying energetics. Using this method we
      investigate the interactions between the hydrophobic peptide M2delta and a model
      membrane. The simulations show that starting from an extended conformation in the
      aqueous phase, the peptide first adsorbs onto the membrane surface, while
      acquiring an ordered helical structure. This is followed by formation of a
      helical-hairpin and insertion into the membrane. The observed path is in
      agreement with contemporary understanding of peptide insertion into biological
      membranes. Two stable orientations of membrane-associated M2delta were obtained:
      transmembrane (TM) and surface, and the value of the water-to-membrane transfer
      free energy of each of them is in agreement with calculations and measurements on
      similar cases. M2delta is most stable in the TM orientation, where it assumes a
      helical conformation with a tilt of 14 degrees between the helix principal axis
      and the membrane normal. The peptide conformation agrees well with the
      experimental data; average root-mean-square deviations of 2.1 A compared to
      nuclear magnetic resonance structures obtained in detergent micelles and
      supported lipid bilayers. The average orientation of the peptide in the membrane
      in the most stable configurations reported here, and in particular the value of
      the tilt angle, are in excellent agreement with the ones calculated using the
      continuum-solvent model and the ones observed in the nuclear magnetic resonance
      studies. This suggests that the method may be used to predict the three
      dimensional structure of TM peptides.

PMID- 14645041
TI  - Effects of base substitutions in an RNA hairpin from molecular dynamics and free
      energy simulations.
AB  - Contributions of individual interactions in the GGCGCAAGCC hairpin containing a
      GCAA tetraloop were studied by computer simulations using base substitutions. The
      G in the first tetraloop position was replaced by inosine (I) or adenosine (A),
      and the G in the C-G basepair closing the tetraloop was replaced by I. These
      substitutions eliminate particular hydrogen bonds proposed in the nuclear
      magnetic resonance model of the GCAA tetraloop. Molecular dynamics simulations of
      the GCAA tetraloop in aqueous solvent displayed a well-defined hydrogen pattern
      between the first and last loop nucleotides (G and A) stabilized by a bridging
      water molecule. Substitution of G-->I in the basepair closing the tetraloop did
      not significantly influence the loop structure and dynamics. The ICAA loop
      maintained the overall structure, but displayed variation in the hydrogen-bond
      network within the tetraloop itself. Molecular dynamics simulations of the ACAA
      loop led to conformational heterogeneity of the resulting structures. Changes of
      hairpin formation free energy associated with substitutions of individual bases
      were calculated by the free energy perturbation method. The calculated decrease
      of the hairpin stability upon G-->I substitution in the C-G basepair closing the
      tetraloop was in good agreement with experimental thermodynamic data. Our
      theoretical estimates for G-->I and G-->A mutations located in the tetraloop
      suggest larger loop destabilization than corresponding experimental results. The
      extent of conformational sampling of the structures resulting from base
      substitutions and its impact on the calculated free energy was discussed.

PMID- 14645042
TI  - Kinetics of prion growth.
AB  - We study the kinetics of prion fibril growth, described by the nucleated
      polymerization model analytically and by means of numerical experiments. The
      elementary processes of prion fibril formation lead us to a set of differential
      equations for the number of fibrils, their total mass, and the number of prion
      monomers. In difference to previous studies we analyze this set by explicitly
      taking into account the time-dependence of the prion monomer concentration. The
      theoretical results agree with experimental data, whereas the generally accepted
      hypothesis of constant monomer concentration leads to a fibril growth behavior
      which is not in agreement with experiments. The obtained size distribution of the
      prion fibril aggregates is shifted significantly toward shorter lengths as
      compared to earlier results, which leads to a enhanced infectivity of the prion
      material. Finally, we study the effect of filtering of the inoculated material on
      the incubation time of the disease.

PMID- 14645043
TI  - Permeation across hydrated DPPC lipid bilayers: simulation of the titrable
      amphiphilic drug valproic acid.
AB  - Valproic acid is a short branched fatty acid used as an anticonvulsant drug whose
      therapeutic action has been proposed to arise from membrane-disordering
      properties. Static and kinetic properties of valproic acid interacting with fully
      hydrated dipalmitoyl phosphatidylcholine lipid bilayers are studied using
      molecular-dynamics simulations. We calculate spatially resolved free energy
      profiles and local diffusion coefficients using the distance between the bilayer
      and valproic acid respective centers-of-mass along the bilayer normal as reaction
      coordinate. To investigate the pH dependence, we calculate profiles for the
      neutral valproic acid as well as its water-soluble anionic conjugate base
      valproate. The local diffusion constants for valproate/valproic acid along the
      bilayer normal are found to be approximately 10(-6) to 10(-5) cm2 s(-1). Assuming
      protonation of valproic acid upon association with--or insertion into--the lipid
      bilayer, we calculate the permeation coefficient to be approximately 2.0 10(-3)
      cm s(-1), consistent with recent experimental estimates of fast fatty acid
      transport. The ability of the lipid bilayer to sustain local defects such as
      water intrusions stresses the importance of going beyond mean field and taking
      into account correlation effects in theoretical descriptions of bilayer
      translocation processes.

PMID- 14645044
TI  - A computational study of the open and closed forms of the N-lobe human serum
      transferrin apoprotein.
AB  - Human serum transferrin tightly binds ferric ions in the blood stream but is able
      to release them in cells by a process involving receptor-mediated endocytosis and
      decrease in pH. Iron binding and release are accompanied by a large conformation
      change. In this study, we investigate theoretically the open and closed forms of
      the N-lobe human serum transferrin apoprotein by performing pKa calculations and
      molecular dynamics and free-energy simulations. In agreement with the hypothesis
      based on the x-ray crystal structures, our calculations show that there is a
      shift in the pKa values of the lysines forming the dilysine trigger when the
      conformation changes. We argue, however, that simple electrostatic repulsion
      between the lysines is not sufficient to trigger domain opening and, instead,
      propose an alternative explanation for the dilysine-trigger effect. Analysis of
      the molecular dynamics and free-energy results indicate that the open form is
      more mobile than the closed form and is much more stable at pH 5.3, in large part
      due to entropic effects. Despite a lower free energy, the dynamics simulation of
      the open form shows that it is flexible enough to sample conformations that are
      consistent with iron binding.

PMID- 14645045
TI  - Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers
      during low-frequency sonophoresis.
AB  - Interactions of acoustic cavitation bubbles with biological tissues play an
      important role in biomedical applications of ultrasound. Acoustic cavitation
      plays a particularly important role in enhancing transdermal transport of
      macromolecules, thereby offering a noninvasive mode of drug delivery
      (sonophoresis). Ultrasound-enhanced transdermal transport is mediated by inertial
      cavitation, where collapses of cavitation bubbles microscopically disrupt the
      lipid bilayers of the stratum corneum. In this study, we describe a theoretical
      analysis of the interactions of cavitation bubbles with the stratum corneum lipid
      bilayers. Three modes of bubble-stratum corneum interactions including shock wave
      emission, microjet penetration into the stratum corneum, and impact of microjet
      on the stratum corneum are considered. By relating the mechanical effects of
      these events on the stratum corneum structure, the relationship between the
      number of cavitation events and collapse pressures with experimentally measured
      increase in skin permeability was established. Theoretical predictions were
      compared to experimentally measured parameters of cavitation events.

PMID- 14645046
TI  - The role of the unfolded state in hairpin stability.
AB  - The effects of a T3S mutation on the stability of a 3:5 beta-hairpin forming
      peptide (YITNSNGTWT) are investigated. Molecular dynamics simulations in explicit
      water indicate that the wild-type peptide forms a stable hairpin whereas the T3S
      mutant does not, in agreement with the experimental data. Thermodynamic
      integration calculations for the mutation of Thr to Ser suggest that the free
      energy changes in the folded state are small, but the corresponding changes in
      the unfolded state are large and favorable. One of the main reasons for the
      difference appears to be the formation of a stable cluster involving the Tyr1 and
      Ser3 hydroxyl groups and their interaction with the C-terminal carboxylate group,
      which was observed after unfolding of the T3S mutant. Further analysis of the
      side-chain preferences of Thr and Ser indicate that the corresponding cluster in
      the wild-type peptide is unstable due to the high preference of the Thr chi1
      dihedral for g+ states, which appeared to be incompatible with formation of a
      stable cluster. The results suggest that one should consider the nature of the
      unfolded state when attempting to fully explain the effects of mutations on
      hairpin stability.

PMID- 14645047
TI  - Competition between protein folding and aggregation with molecular chaperones in
      crowded solutions: insight from mesoscopic simulations.
AB  - The living cell is inherently crowded with proteins and macromolecules. To avoid
      aggregation of denatured proteins in the living cell, molecular chaperones play
      important roles. Here we introduce a simple model to describe crowded protein
      solutions with chaperone-like species based on a dynamic density functional
      theory. As predicted by others, our simulations show that macromolecular crowding
      enhances the association of proteins and chaperones. However, when the intrinsic
      folding rate of the protein is slow, it is possible that crowding also enhances
      aggregation of proteins. The results of simulation suggest that, when the
      concentration of the crowding agent is as high as that in the cell, the
      association of the protein and unbound chaperone becomes correlated with the
      aggregation process, and that the protein-bound chaperones efficiently destroy
      the potential nuclei of aggregates and thus prevent the aggregation.

PMID- 14645048
TI  - Multiscale study of counterion-induced attraction and bundle formation of F-actin
      using an Ising-like mean-field model.
AB  - An Ising-like counterion-binding model is developed and solved by a mean-field
      method. For G-actin, the calculated affinity constants of all the binding sites
      ranging from loose to tight binding match the experimental data. The model is
      used to calculate the interaction energy between two F-actin filaments. Within a
      certain counterion concentration range, a rapidly decaying attractive force
      between two parallel filaments is produced not only by the correlation of the
      counterion distributions on the two filaments, but also by the correlation of the
      configurations of the two filaments with fixed counterion positions, which has
      been ignored in previous calculations. The bundling energy depends strongly on
      the configuration of the filaments. Upon bundling, the tightly bound counterion
      site is not affected, but the medium and loosely bound ones are. The model
      reproduces the observed minimal divalent counterion concentration for bundling,
      and naturally predicts the resolubilization of bundles which is seen in recent
      experiments. At the optimal counterion concentration, we obtain a bundling energy
      of approximately -0.01 eV per monomer along the filament. The counterion valence
      strongly affects the optimal counterion concentration, but has only minor effects
      on the optimal bundling energy. We show that the attractive potential between
      filaments can be simplified as the sum of interactions between their monomers.
      This simplification makes it possible to calculate the exact free energy of a two
      F-actin-filament system. We are thus able to probe the effects of filament length
      on F-actin bundling and obtain a critical length for bundling of 59 monomers at 1
      microM monomer concentration and pH=7.2.

PMID- 14645049
TI  - Protein aggregation/folding: the role of deterministic singularities of sequence
      hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and
      Abeta(1-40).
AB  - The problem of protein folding vs. aggregation was investigated in
      acylphosphatase and the amyloid protein Abeta(1-40) by means of nonlinear signal
      analysis of their chain hydrophobicity. Numerical descriptors of recurrence
      patterns provided the basis for statistical evaluation of folding/aggregation
      distinctive features. Static and dynamic approaches were used to elucidate
      conditions coincident with folding vs. aggregation using comparisons with known
      protein secondary structure classifications, site-directed mutagenesis studies of
      acylphosphatase, and molecular dynamics simulations of amyloid protein, Abeta(1
      40). The results suggest that a feature derived from principal component space
      characterized by the smoothness of singular, deterministic hydrophobicity patches
      plays a significant role in the conditions governing protein aggregation.

PMID- 14645050
TI  - Model of bacterial band formation in aerotaxis.
AB  - Aerotaxis is a particular form of "energy taxis". It is based on a largely
      elusive signal transduction machinery. In aerotaxis, oxygen dissolved in water
      plays the role of both attractant (at moderate concentrations) and repellent (at
      high and low concentrations). Cells swimming from favorable oxygen concentrations
      into regions with unfavorable concentrations increase the frequency of reversals,
      turn back into the favorable domain, and become effectively trapped there. At the
      same time, bacteria consume oxygen, creating an oxygen gradient. This behavior
      leads to a pattern formation phenomenon: bacteria self-organize into a dense band
      at a certain distance from the air-water interface. We incorporate experimental
      observations of the aerotactic bacterium, Azospirillum brasilense, into a
      mathematical model. The model consists of a system of differential equations
      describing swimming bacterial cells and diffusing oxygen. The cells' frequency of
      reversals depends on the concentration of oxygen and its time derivative while
      oxygen is depleted by the bacteria. We suggest a hypothetical model of energy
      sensing mediated by aerotactic receptors Aer and Tsr. Computer simulations and
      analysis of the model equations allow comparisons of theoretical and experimental
      results and provide insight into the mechanisms of bacterial pattern formation
      and underlying signal transduction machinery. We make testable predictions about
      position and density of the bacterial band.

PMID- 14645051
TI  - Saltatory and continuous calcium waves and the rapid buffering approximation.
AB  - Calcium waves propagate inside cells due to a regenerative mechanism known as
      calcium-induced calcium release. Buffer-mediated calcium diffusion in the cytosol
      plays a crucial role in the process. However, most models of calcium waves either
      treat buffers phenomenologically or assume that they are in equilibrium with
      calcium (the rapid buffering approximation). In this article we address the issue
      of whether this approximation provides a good description of wave propagation. We
      first compare the timescales present in the problem, and determine the situations
      in which the equilibrium hypothesis fails. We then present a series of numerical
      studies based on the simple fire-diffuse-fire model of wave propagation. We find
      that the differences between the full and reduced descriptions may lead to errors
      that are above experimental resolution even for relatively fast buffers in the
      case of saltatory waves. Conversely, in the case of continuous waves, the
      approximation may give accurate results even for relatively slow buffers.

PMID- 14645052
TI  - A perspective on mechanisms of protein tetramer formation.
AB  - Homotetrameric proteins can assemble by several different pathways, but have only
      been observed to use one, in which two monomers associate to form a homodimer,
      and then two homodimers associate to form a homotetramer. To determine why this
      pathway should be so uniformly dominant, we have modeled the kinetics of
      tetramerization for the possible pathways as a function of the rate constants for
      each step. We have found that competition with the other pathways, in which
      homotetramers can be formed either by the association of two different types of
      homodimers or by the successive addition of monomers to homodimers and
      homotrimers, can cause substantial amounts of protein to be trapped as
      intermediates of the assembly pathway. We propose that this could lead to
      undesirable consequences for an organism, and that selective pressure may have
      caused homotetrameric proteins to evolve to assemble by a single pathway.

PMID- 14645053
TI  - Dynamics of the cell cycle: checkpoints, sizers, and timers.
AB  - We have developed a generic mathematical model of a cell cycle signaling network
      in higher eukaryotes that can be used to simulate both the G1/S and G2/M
      transitions. In our model, the positive feedback facilitated by CDC25 and wee1
      causes bistability in cyclin-dependent kinase activity, whereas the negative
      feedback facilitated by SKP2 or anaphase-promoting-complex turns this bistable
      behavior into limit cycle behavior. The cell cycle checkpoint is a Hopf
      bifurcation point. These behaviors are coordinated by growth and division to
      maintain normal cell cycle and size homeostasis. This model successfully
      reproduces sizer, timer, and the restriction point features of the eukaryotic
      cell cycle, in addition to other experimental findings.

PMID- 14645054
TI  - Theoretical investigation of infrared spectra and pocket dynamics of
      photodissociated carbonmonoxy myoglobin.
AB  - Molecular dynamics simulations of the photodissociated state of carbonmonoxy
      myoglobin (MbCO) are presented using a fluctuating charge model for CO. A new
      three-point charge model is fitted to high-level ab initio calculations of the
      dipole and quadrupole moment functions taken from the literature. The infrared
      spectrum of the CO molecule in the heme pocket is calculated using the dipole
      moment time autocorrelation function and shows good agreement with experiment. In
      particular, the new model reproduces the experimentally observed splitting of the
      CO absorption spectrum. The splitting of 3-7 cm(-1) (compared to the experimental
      value of 10 cm(-1)) can be directly attributed to the two possible orientations
      of CO within the docking site at the edge of the distal heme pocket (the B
      states), as previously suggested on the basis of experimental femtosecond time
      resolved infrared studies. Further information on the time evolution of the
      position and orientation of the CO molecule is obtained and analyzed. The
      calculated difference in the free energy between the two possible orientations
      (Fe...CO and Fe...OC) is 0.3 kcal mol(-1) and agrees well with the experimentally
      estimated value of 0.29 kcal mol(-1). A comparison of the new fluctuating charge
      model with an established fixed charge model reveals some differences that may be
      critical for the correct prediction of the infrared spectrum and energy barriers.
      The photodissociation of CO from the myoglobin mutant L29F using the new model
      shows rapid escape of CO from the distal heme pocket, in good agreement with
      recent experimental data. The effect of the protein environment on the multipole
      moments of the CO ligand is investigated and taken into account in a refined
      model. Molecular dynamics simulations with this refined model are in agreement
      with the calculations based on the gas-phase model. However, it is demonstrated
      that even small changes in the electrostatics of CO alter the details of the
      dynamics.

PMID- 14645055
TI  - Structure of sphingomyelin bilayers: a simulation study.
AB  - We have carried out a molecular dynamics simulation of a hydrated 18:0
      sphingomyelin lipid bilayer. The bilayer contained 1600 sphingomyelin (SM)
      molecules, and 50,592 water molecules. After construction and initial
      equilibration, the simulation was run for 3.8 ns at a constant temperature of 50
      degrees C and a constant pressure of 1 atm. We present properties of the bilayer
      calculated from the simulation, and compare with experimental data and with
      properties of dipalmitoyl phosphatidylcholine (DPPC) bilayers. The SM bilayers
      are significantly more ordered and compact than DPPC bilayers at the same
      temperature. SM bilayers also exhibit significant intramolecular hydrogen bonding
      between phosphate ester oxygen and hydroxyl hydrogen atoms. This results in a
      decreased hydration in the polar region of the SM bilayer compared with DPPC.
      Since our simulation system is very large we have calculated the power spectrum
      of bilayer undulation and peristaltic modes, and we compare these data with
      similar calculations for DPPC bilayers. We find that the SM bilayer has
      significantly larger bending modulus and area compressibility compared to DPPC.

PMID- 14645056
TI  - Molecular simulation study on the influence of dimethylsulfoxide on the structure
      of phospholipid bilayers.
AB  - Molecular dynamics simulations of dipalmitoylphosphatidylcholine (DPPC) lipid
      bilayer/water systems were performed in the presence of dimethylsulfoxide (DMSO)
      at 2, 5, 10, and 100 mol % DMSO (lipid-free basis). The equilibrium structure and
      several dynamic properties were determined for these systems. Results show that
      DMSO penetrates much deeper into the bilayer than water does. It is also found
      that DMSO molecules do not interact with the polar groups of the lipid headgroup,
      but exhibit a preference to remain either directly below the headgroup or in the
      aqueous phase, which is a consequence of the chemical characteristics of DMSO. As
      the temperature increases, a higher DMSO concentration is observed in the bilayer
      side of the interface. The area per headgroup in the presence of DMSO is
      significantly increased from 66.8 A2 for the pure bilayer to as high as 87.0 A2
      at 10 mol % DMSO at 350 K. DMSO hydrogen-bonds strongly with water and exhibits
      unfavorable interactions with the polar headgroups of DPPC, thereby inducing a
      dehydration of the headgroups.

PMID- 14645057
TI  - Molecular dynamics simulations of the E1/E2 transmembrane domain of the Semliki
      Forest virus.
AB  - Transmembrane (TM) helix-helix interactions are important for virus budding and
      fusion. We have developed a simulation strategy that reveals the main features of
      the helical packing between the TM domains of the two glycoproteins E1 and E2 of
      the alpha-virus Semliki Forest virus and that can be extrapolated to sketch TM
      helical packing in other alpha-viruses. Molecular dynamics simulations were
      performed in wild-type and mutant peptides, both isolated and forming E1/E2
      complexes. The simulations revealed that the isolated wild-type E1 peptide formed
      a more flexible helix than the rest of peptides and that the wild-type E1/E2
      complex consists of two helices that intimately pack their N-terminals. The
      residues located at the interhelical interface displayed the typical motif of the
      left-handed coiled-coils. These were small and medium residues as Gly, Ala, Ser,
      and Leu, which also had the possibility to form interhelical Calpha-H...O
      hydrogen bonds. Results from the mutant complexes suggested that correct packing
      is a compromise between these residues at both E1 and E2 interhelical interfaces.
      This compromise allowed prediction of E1-E2 contact residues in the TM spanning
      domain of other alphaviruses even though the sequence identity of E2 peptides is
      low in this domain.

PMID- 14645058
TI  - Stochastic model of autocrine and paracrine signals in cell culture assays.
AB  - Autocrine signaling systems are commonly studied under cell culture conditions.
      In a typical cell culture assay, a layer of liquid medium covers a random two
      dimensional dispersion of cells, which secrete ligands. In a growing number of
      experiments, it is important to characterize the spatial range of autocrine and
      paracrine cell communication. Currently, the spatial distribution of diffusing
      signals can be analyzed only indirectly, from their effects on the intracellular
      signaling or physiological responses of autocrine cells. To directly characterize
      the spatial range of secreted ligands, we propose a stochastic model for
      autocrine cell cultures and analyze it using a combination of analytical and
      computational tools. The two main results derived within the framework of this
      model are 1), an expression for the fraction of autocrine trajectories, i.e., the
      probability for a ligand to be trapped by the same cell from which it has been
      secreted; and 2), an expression for the spatial distribution of trapping points
      of paracrine trajectories. We test these analytical results by stochastic
      simulations with efficient Brownian dynamics code and apply our model to analyze
      the spatial operation of autocrine epidermal growth factor receptor systems.

PMID- 14645059
TI  - Model of intracellular calcium cycling in ventricular myocytes.
AB  - We present a mathematical model of calcium cycling that takes into account the
      spatially localized nature of release events that correspond to experimentally
      observed calcium sparks. This model naturally incorporates graded release by
      making the rate at which calcium sparks are recruited proportional to the whole
      cell L-type calcium current, with the total release of calcium from the
      sarcoplasmic reticulum (SR) being just the sum of local releases. The dynamics of
      calcium cycling is studied by pacing the model with a clamped action potential
      waveform. Experimentally observed calcium alternans are obtained at high pacing
      rates. The results show that the underlying mechanism for this phenomenon is a
      steep nonlinear dependence of the calcium released from the SR on the diastolic
      SR calcium concentration (SR load) and/or the diastolic calcium level in the
      cytosol, where the dependence on diastolic calcium is due to calcium-induced
      inactivation of the L-type calcium current. In addition, the results reveal that
      the calcium dynamics can become chaotic even though the voltage pacing is
      periodic. We reduce the equations of the model to a two-dimensional discrete map
      that relates the SR and cytosolic concentrations at one beat and the previous
      beat. From this map, we obtain a condition for the onset of calcium alternans in
      terms of the slopes of the release-versus-SR load and release-versus-diastolic
      calcium curves. From an analysis of this map, we also obtain an understanding of
      the origin of chaotic dynamics.

PMID- 14645060
TI  - Interactions of the M2delta segment of the acetylcholine receptor with lipid
      bilayers: a continuum-solvent model study.
AB  - M2delta, one of the transmembrane segments of the nicotinic acetylcholine
      receptor, is a 23-amino-acid peptide, frequently used as a model for peptide
      membrane interactions. In this and the companion article we describe studies of
      M2delta-membrane interactions, using two different computational approaches. In
      the present work, we used continuum-solvent model calculations to investigate key
      thermodynamic aspects of its interactions with lipid bilayers. M2delta was
      represented in atomic detail and the bilayer was represented as a hydrophobic
      slab embedded in a structureless aqueous phase. Our calculations show that the
      transmembrane orientation is the most favorable orientation of the peptide in the
      bilayer, in good agreement with both experimental and computational data.
      Moreover, our calculations produced the free energy of association of M2delta
      with the lipid bilayer, which, to our knowledge, has not been reported to date.
      The calculations included 10 structures of M2delta, determined by nuclear
      magnetic resonance in dodecylphosphocholine micelles. All the structures were
      found to be stable inside the lipid bilayer, although their water-to-membrane
      transfer free energies differed by as much as 12 kT. Although most of the
      structures were roughly linear, a single structure had a kink in its central
      region. Interestingly, this structure was found to be the most stable inside the
      lipid bilayer, in agreement with molecular dynamics simulations of the peptide
      and with the recently determined structure of the intact receptor. Our analysis
      showed that the kink reduced the polarity of the peptide in its central region by
      allowing the electrostatic masking of the Gln13 side chain in that area. Our
      calculations also showed a tendency for the membrane to deform in response to
      peptide insertion, as has been previously found for the membrane-active peptides
      alamethicin and gramicidin. The results are compared to Monte Carlo simulations
      of the peptide-membrane system, as presented in the accompanying article.

PMID- 14645061
TI  - What really prevents proton transport through aquaporin? Charge self-energy
      versus proton wire proposals.
AB  - The nature of the control of water/proton selectivity in biological channels is a
      problem of a fundamental importance. Most studies of this issue have proposed
      that an interference with the orientational requirements of the so-called proton
      wire is the source of selectivity. The elucidation of the structures of
      aquaporins, which have evolved to prevent proton transfer (PT), provided a clear
      benchmark for exploring the selectivity problem. Previous simulations of this
      system have not examined, however, the actual issue of PT, but only considered
      the much simpler task of the transfer of water molecules. Here we take aquaporin
      as a benchmark and quantify the origin of the water/proton selectivity in this
      and related systems. This is done by evaluating in a consistent way the free
      energy profile for transferring a proton along the channel and relating this
      profile to the relevant PT rate constants. It is found that the water/proton
      selectivity is controlled by the change in solvation free energy upon moving the
      charged proton from water to the channel. The reason for the focus on the elegant
      concept of the proton wire and the related Grotthuss-type mechanism is also
      considered. It is concluded that these mechanisms are clearly important in cases
      with flat free energy surfaces (e.g., in bulk water, in gas phase water chains,
      and in infinitely long channels). However, in cases of biological channels, the
      actual PT mechanism is much less important than the energetics of transferring
      the proton charge from water to different regions in the channels.

PMID- 14645062
TI  - FTIR study of ATP-induced changes in Na+/K+-ATPase from duck supraorbital glands.
AB  - The Na+/K+-ATPase uses energy from the hydrolysis of ATP to pump Na+ ions out of
      and K+ ions into the cell. ATP-induced conformational changes in the protein have
      been examined in the Na+/K+-ATPase isolated from duck supraorbital salt glands
      using Fourier transform infrared spectroscopy. Both standard transmission and
      attenuated total internal reflection sample geometries have been employed. Under
      transmission conditions, enzyme at 75 mg/ml was incubated with dimethoxybenzoin
      caged ATP. ATP was released by flashing with a UV laser pulse at 355 nm, which
      resulted in a large change in the amide I band. The absorbance at 1659 cm(-1)
      decreased with a concomitant increase in the absorbance at 1620 cm(-1). These
      changes are consistent with a partial conversion of protein secondary structure
      from alpha-helix to beta-sheet. The changes were approximately 8% of the total
      absorbance, much larger than those seen with other P-type ATPases. Using
      attenuated total internal reflection Fourier transform infrared spectroscopy, the
      decrease in absorbance at approximately 1650 cm(-1) was titrated with ATP, and
      the titration midpoint K0.5 was determined under different ionic conditions. In
      the presence of metal ions (Na+, Na+ and K+, or Mg2+), K0.5 was on the order of a
      few microM. In the absence of these ions, K0.5 was an order of magnitude lower
      (0.1 microM), indicating a higher apparent affinity. This effect suggests that
      the equilibrium for the ATP-induced conformational changes is dependent on the
      presence of metal ions.

PMID- 14645063
TI  - Residue ionization and ion transport through OmpF channels.
AB  - Single trimeric channels of the general bacterial porin, OmpF, were reconstituted
      into planar lipid membranes and their conductance, selectivity, and open-channel
      noise were studied over a wide range of proton concentrations. From pH 1 to pH
      12, channel transport properties displayed three characteristic regimes. First,
      in acidic solutions, channel conductance is a strong function of pH; it increases
      by approximately threefold as the proton concentration decreases from pH 1 to pH
      5. This rise in conductance is accompanied by a sharp increase in cation
      transport number and by pronounced open-channel low-frequency current noise with
      a peak at approximately pH 2.5. Random stepwise transients with amplitudes at
      approximately 1/5 of the monomer conductance are major contributors to this
      noise. Second, over the middle range (pH 5/pH 9), channel conductance and
      selectivity stay virtually constant; open channel noise is at its minimum. Third,
      over the basic range (pH 9/pH 12), channel conductance and cation selectivity
      start to grow again with an onset of a higher frequency open-channel noise. We
      attribute these effects to the reversible protonation of channel residues whose
      pH-dependent charge influences transport by direct interactions with ions passing
      through the channel.

PMID- 14645064
TI  - Electrophysiological analysis of the yeast V-type proton pump: variable coupling
      ratio and proton shunt.
AB  - Isolated vacuoles from the yeast Saccharomyces cerevisiae were examined in the
      whole-vacuole mode of patch recording, to get a detailed functional description
      of the vacuolar proton pump, the V-ATPase. Functioning of the V-ATPase was
      characterized by its current-voltage (I-V) relationship, obtained for various
      levels of vacuolar and cytosolic pH. I-V curves for the V-ATPase were computed as
      the difference between I-V curves obtained with the pump switched on (ATP, ADP,
      and Pi present) or off (no ATP). These difference current-voltage relationships
      usually crossed the voltage axis within the experimental range (from -80 to +80
      mV), thus measuring the reversal voltage (ER) for the V-ATPase, which could be
      compared with the standing ion gradients and free energy of ATP hydrolysis, to
      calculate the apparent pump stoichiometry or coupling ratio: the number of
      protons transported for each ATP molecule hydrolyzed. This ratio was found to
      depend strongly upon the pH difference (DeltapH) across the vacuolar membrane,
      being approximately 2H+/ATP at high DeltapH (4 pH units) and increasing to
      >4H+/ATP for small or zero DeltapH. That result is in quantitative agreement with
      previous determinations on plant vacuoles. Considerations of purely electrical
      behavior, together with the physical properties of a recent detailed structural
      model for V-ATPases, led to a linear equivalent circuit--which quantitatively
      accounts for all observations of variable coupling ratios in fungal and plant V
      ATPases by variations of the conductance for bona fide proton pumping (GP)
      through the ATPase relative to independent proton shunting (GS) through the same
      protein.

PMID- 14645065
TI  - Ca2+-dependent excitation-contraction coupling triggered by the heterologous
      cardiac/brain DHPR beta2a-subunit in skeletal myotubes.
AB  - Molecular determinants essential for skeletal-type excitation-contraction (EC)
      coupling have been described in the cytosolic loops of the dihydropyridine
      receptor (DHPR) alpha1S pore subunit and in the carboxyl terminus of the skeletal
      specific DHPR beta1a-subunit. It is unknown whether EC coupling domains present
      in the beta-subunit influence those present in the pore subunit or if they act
      independent of each other. To address this question, we investigated the EC
      coupling signal that is generated when the endogenous DHPR pore subunit alpha1S
      is paired with the heterologous heart/brain DHPR beta2a-subunit. Studies were
      conducted in primary cultured myotubes from beta1 knockout (KO), ryanodine
      receptor type 1 (RyR1) KO, ryanodine receptor type 3 (RyR3) KO, and double
      RyR1/RyR3 KO mice under voltage clamp with simultaneous monitoring of confocal
      fluo-4 fluorescence. The beta2a-mediated Ca2+ current recovered in beta1 KO
      myotubes lacking the endogenous DHPR beta1a-subunit verified formation of the
      alpha1S/beta1a pair. In myotube genotypes which express no or low-density L-type
      Ca2+ currents, namely beta1 KO and RyR1 KO, beta2a overexpression recovered a
      wild-type density of nifedipine-sensitive Ca2+ currents with a slow activation
      kinetics typical of skeletal myotubes. Concurrent with Ca2+ current recovery,
      there was a drastic reduction of voltage-dependent, skeletal-type EC coupling and
      emergence of Ca2+ transients triggered by the Ca2+ current. A comparison of
      beta2a overexpression in RyR3 KO, RyR1 KO, and double RyR1/RyR3 KO myotubes
      concluded that both RyR1 and RyR3 isoforms participated in Ca2+-dependent Ca2+
      release triggered by the beta2a-subunit. In beta1 KO and RyR1 KO myotubes, the
      Ca2+-dependent EC coupling promoted by beta2a overexpression had the following
      characteristics: 1), L-type Ca2+ currents had a wild-type density; 2), Ca2+
      transients activated much slower than controls overexpressing beta1a, and the
      rate of fluorescence increase was consistent with the activation kinetics of the
      Ca2+ current; 3), the voltage dependence of the Ca2+ transient was bell-shaped
      and the maximum was centered at approximately +30 mV, consistent with the voltage
      dependence of the Ca2+ current; and 4), Ca2+ currents and Ca2+ transients were
      fully blocked by nifedipine. The loss in voltage-dependent EC coupling promoted
      by beta2a was inferred by the drastic reduction in maximal Ca2+ fluorescence at
      large positive potentials (DeltaF/Fmax) in double dysgenic/beta1 KO myotubes
      overexpressing the pore mutant alpha1S (E1014K) and beta2a. The data indicate
      that beta2a, upon interaction with the skeletal pore subunit alpha1S, overrides
      critical EC coupling determinants present in alpha1S. We propose that the
      alpha1S/beta pair, and not the alpha1S-subunit alone, controls the EC coupling
      signal in skeletal muscle.

PMID- 14645066
TI  - Lipid dynamics and domain formation in model membranes composed of ternary
      mixtures of unsaturated and saturated phosphatidylcholines and cholesterol.
AB  - In recent years, the implication of sphingomyelin in lipid raft formation has
      intensified the long sustained interest in this membrane lipid. Accumulating
      evidences show that cholesterol preferentially interacts with sphingomyelin,
      conferring specific physicochemical properties to the bilayer membrane. The
      molecular packing created by cholesterol and sphingomyelin, which presumably is
      one of the driving forces for lipid raft formation, is known in general to differ
      from that of cholesterol and phosphatidylcholine membranes. However, in many
      studies, saturated phosphatidylcholines are still considered as a model for
      sphingolipids. Here, we investigate the effect of cholesterol on mixtures of
      dioleoyl-phosphatidylcholine (DOPC) and dipalmitoyl-phosphatidylcholine (DPPC) or
      distearoyl-phosphatidylcholine (DSPC) and compare it to that on mixtures of DOPC
      and sphingomyelin analyzed in previous studies. Giant unilamellar vesicles
      prepared from ternary mixtures of various lipid compositions were imaged by
      confocal fluorescence microscopy and, within a certain range of sterol content,
      domain formation was observed. The assignment of distinct lipid phases and the
      molecular mobility in the membrane bilayer was investigated by fluorescence
      correlation spectroscopy. Cholesterol was shown to affect lipid dynamics in a
      similar way for DPPC and DSPC when the two phospholipids were combined with
      cholesterol in binary mixtures. However, the corresponding ternary mixtures
      exhibited different spatial lipid organization and dynamics. Finally, evidences
      of a weaker interaction of cholesterol with saturated phosphatidylcholines than
      with sphingomyelin (with matched chain length) are discussed.

PMID- 14645067
TI  - Structural and functional roles of HIV-1 gp41 pretransmembrane sequence
      segmentation.
AB  - The membrane-proximal segment connecting the helical core with the transmembrane
      anchor of human immunodeficiency virus type 1 gp41 is accessible to broadly
      neutralizing antibodies and plays a crucial role in fusion activity. New
      predictive approaches including computation of interfacial affinity and the
      corresponding hydrophobic moments suggest that this region is functionally
      segmented into two consecutive subdomains: one amphipathic at the N-terminal side
      and one fully interfacial at the C-terminus. The N-terminal subdomain would
      extend alpha-helices from the preceding carboxy-terminal heptad repeat and
      provide, at the same time, a hydrophobic-at-interface surface. Experiments were
      performed to compare a wild-type representing pretransmembrane peptide with a
      nonamphipathic defective sequence, which otherwise conserved interfacial
      hydrophobicity at the carboxy-subdomain. Results confirmed that both penetrated
      equally well into lipid monolayers and both were able to partition into membrane
      interfaces. However only the functional sequence: 1), adopted helical structures
      in solution and in membranes; 2), formed homo-oligomers in solution and
      membranes; and 3), inhibited gp41-induced cell-cell fusion. These data support
      two roles for gp41 aromatic-rich pretransmembrane sequence: 1), oligomerization
      of gp41; and 2), immersion into the viral membrane interface. Accessibility to
      membrane interfaces and subsequent adoption of the low-energy structure may
      augment helical bundle formation and perhaps be related to a concomitant loss of
      immunoreactivity. These results may have implications in the development of HIV-1
      fusion inhibitors and vaccines.

PMID- 14645068
TI  - A phospholipid bilayer supported under a polymerized Langmuir film.
AB  - Phospholipid single bilayers supported on a hydrophilic solid substrate are
      extensively used in the study of the interaction between model membranes and
      proteins or polypeptides. In this article, the formation of a single
      dimyristoylphosphatidylcholine (DMPC) bilayer under an octadecyltrimethoxysilane
      (OTMS) polymerized Langmuir monolayer at the air-water interface is followed by
      Brewster angle microscopy (BAM) and polarization-modulated infrared reflection
      absorption spectroscopy (PM-IRRAS). The formation of the bilayer is initiated by
      injection of dimyristoylphosphatidylcholine small unilamellar vesicles into the
      aqueous subphase. Brewster angle microscopy allows visualization of the kinetics
      of formation and the homogeneity of the bilayer. Spectral simulations of the
      polarization-modulated infrared reflection absorption spectroscopy spectra reveal
      that the bilayer thickness is 39 +/- 5 A. This system constitutes the first
      example of a phospholipid bilayer on a "nanoscopic" support and opens the way to
      studies involving supported bilayers using powerful experimental techniques such
      as x-ray reflectivity, vibrational spectroscopies, or Brewster angle microscopy.

PMID- 14645069
TI  - Sterol structure and sphingomyelin acyl chain length modulate lateral packing
      elasticity and detergent solubility in model membranes.
AB  - Membrane microdomains, such as caveolae and rafts, are enriched in cholesterol
      and sphingomyelin, display liquid-ordered phase properties, and putatively
      function as protein organizing platforms. The goal of this investigation was to
      identify sterol and sphingomyelin structural features that modulate surface
      compression and solubilization by detergent because liquid-ordered phase displays
      low lateral elasticity and resists solubilization by Triton X-100. Compared to
      cholesterol, sterol structural changes involved either altering the polar
      headgroup (e.g., 6-ketocholestanol) or eliminating the isooctyl hydrocarbon tail
      (e.g., 5-androsten-3beta-ol). Synthetic changes to sphingomyelin resulted in
      homogeneous acyl chains of differing length but of biological relevance. Using a
      Langmuir surface balance, surface compressional moduli were assessed at various
      surface pressures including those (pi > or =30 mN/m) that mimic biomembrane
      conditions. Sphingomyelin-sterol mixtures generally were less elastic in a
      lateral sense than chain-matched phosphatidylcholine-sterol mixtures at
      equivalent high sterol mole fractions. Increasing content of 6-ketocholestanol or
      5-androsten-3beta-ol in sphingomyelin decreased lateral elasticity but much less
      effectively than cholesterol. Our results indicate that cholesterol is ideally
      structured for maximally reducing the lateral elasticity of membrane
      sphingolipids, for enabling resistance to Triton X-100 solubilization, and for
      interacting with sphingomyelins that contain saturated acyl chains similar in
      length to their sphingoid bases.

PMID- 14645070
TI  - Phospholipid complexation and association with apolipoprotein C-II: insights from
      mass spectrometry.
AB  - The interactions between phospholipid molecules in suspensions have been studied
      by using mass spectrometry. Electrospray mass spectra of homogeneous preparations
      formed from three different phospholipid molecules demonstrate that under certain
      conditions interactions between 90 and 100 lipid molecules can be preserved. In
      the presence of apolipoprotein C-II, a phospholipid binding protein, a series of
      lipid molecules and the protein were observed in complexes. The specificity of
      binding was demonstrated by proteolysis; the resulting mass spectra reveal lipid
      bound peptides that encompass the proposed lipid-binding domain. The mass spectra
      of heterogeneous suspensions and their complexes with apolipoprotein C-II
      demonstrate that the protein binds simultaneously to two different phospholipids.
      Moreover, when apolipoprotein C-II is added to lipid suspensions formed with
      local concentrations of the same lipid molecule, the protein is capable of
      remodeling the distribution to form one that is closer to a statistical
      arrangement. These observations demonstrate a capacity for apolipoprotein C-II to
      change the topology of the phospholipid surface. More generally, these results
      highlight the fact that mass spectrometry can be used to probe lipid interactions
      in both homogeneous and heterogeneous suspensions and demonstrate reorganization
      of the distribution of lipids upon surface binding of apolipoprotein C-II.

PMID- 14645071
TI  - Prefission constriction of Golgi tubular carriers driven by local lipid
      metabolism: a theoretical model.
AB  - Membrane transport within mammalian cells is mediated by small vesicular as well
      as large pleiomorphic transport carriers (TCs). A major step in the formation of
      TCs is the creation and subsequent narrowing of a membrane neck connecting the
      emerging carrier with the initial membrane. In the case of small vesicular TCs,
      neck formation may be directly induced by the coat proteins that cover the
      emerging vesicle. However, the mechanism underlying the creation and narrowing of
      a membrane neck in the generation of large TCs remains unknown. We present a
      theoretical model for neck formation based on the elastic model of membranes. Our
      calculations suggest a lipid-driven mechanism with a central role for
      diacylglycerol (DAG). The model is applied to a well-characterized in vitro
      system that reconstitutes TC formation from the Golgi complex, namely the
      pearling and fission of Golgi tubules induced by CtBP/BARS, a protein that
      catalyzes the conversion of lysophosphatidic acid into phosphatidic acid. In view
      of the importance of a PA-DAG cycle in the formation of Golgi TCs, we assume that
      the newly formed phosphatidic acid undergoes rapid dephosphorylation into DAG.
      DAG possesses a unique molecular shape characterized by an extremely large
      negative spontaneous curvature, and it redistributes rapidly between the membrane
      monolayers and along the membrane surface. Coupling between local membrane
      curvature and local lipid composition results, by mutual enhancement, in
      constrictions of the tubule into membrane necks, and a related inhomogeneous
      lateral partitioning of DAG. Our theoretical model predicts the exact dimensions
      of the constrictions observed in the pearling Golgi tubules. Moreover, the model
      is able to explain membrane neck formation by physiologically relevant mole
      fractions of DAG.

PMID- 14645072
TI  - Interactions of anionic phospholipids and phosphatidylethanolamine with the
      potassium channel KcsA.
AB  - Fluorescence quenching methods have been used to study interactions of anionic
      phospholipids with the potassium channel KcsA from Streptomyces lividans.
      Quenching of the Trp fluorescence of KcsA reconstituted into mixtures of
      dioleoylphosphatidylcholine (DOPC) and an anionic phospholipid with
      dibromostearoyl chains is more marked at low mole fractions of the brominated
      anionic phospholipid than is quenching in mixtures of
      dibromostearoylphosphatidylcholine and nonbrominated anionic lipid. The quenching
      data are consistent with two classes of binding site for lipid on KcsA, one set
      corresponding to annular binding sites around KcsA to which DOPC and two-chain
      anionic phospholipids bind with similar affinities, the other set (non-annular
      sites) corresponding to sites at which anionic phospholipids can bind but from
      which DOPC is either excluded or binds with very low affinity. The binding
      constant for tetraoleoylcardiolipin at the annular sites is significantly less
      than that for DOPC, being comparable to that for
      dioleoylphosphatidylethanolamine. Tetraoleoylcardiolipin binds with highest
      affinity to the non-annular sites, the affinity for dioleoylphosphatidylglycerol
      being the lowest. The affinity for dioleoylphosphatidylserine decreases at high
      ionic strength, suggesting that electrostatic interactions between the anionic
      phospholipid headgroup and positively charged residues on KcsA are important for
      binding at the non-annular site. The effect of ionic strength on the binding of
      phosphatidic acid is less marked than on phosphatidylserine. The value of the
      binding constant for the non-annular site depends on the extent of Trp
      fluorescence quenching following from binding at the non-annular site. It is
      suggested that the non-annular site to which binding is detected in the
      fluorescence quenching experiments corresponds to the binding site for
      phosphatidylglycerol detected at monomer-monomer interfaces in x-ray diffraction
      studies.

PMID- 14645073
TI  - Liposomes, disks, and spherical micelles: aggregate structure in mixtures of gel
      phase phosphatidylcholines and poly(ethylene glycol)-phospholipids.
AB  - Poly(ethylene glycol) (PEG) decorated lipid bilayers are widely used in
      biomembrane and pharmaceutical research. The success of PEG-lipid stabilized
      liposomes in drug delivery is one of the key factors for the interest in these
      polymer/lipid systems. From a more fundamental point of view, it is essential to
      understand the effect of the surface grafted polymers on the physical-chemical
      properties of the lipid bilayer. Herein we have used cryo-transmission electron
      microscopy and dynamic light scattering to characterize the aggregate structure
      and phase behavior of mixtures of PEG-lipids and distearoylphosphatidylcholine or
      dipalmitoylphosphatidylcholine. The PEG-lipids contain PEG of molecular weight
      2000 or 5000. We show that the transition from a dispersed lamellar phase
      (liposomes) to a micellar phase consisting of small spherical micelles occurs via
      the formation of small discoidal micelles. The onset of disk formation already
      takes place at low PEG-lipid concentrations (<5 mol %) and the size of the disks
      decreases as more PEG-lipid is added to the lipid mixture. We show that the
      results from cryo-transmission electron microscopy correlate well with those
      obtained from dynamic light scattering and that the disks are well described by
      an ideal disk model. Increasing the temperature, from 25 degrees C to above the
      gel-to-liquid crystalline phase transition temperature for the respective lipid
      mixtures, has a relatively small effect on the aggregate structure.

PMID- 14645074
TI  - Molecular orientation and conformation of phosphatidylinositides in membrane
      mimetics using variable angle sample spinning (VASS) NMR.
AB  - For many biological molecules, determining their geometry as they exist in a
      membrane environment is a crucial step in understanding their function. Variable
      angle sample spinning (VASS) NMR provides a new route to obtaining geometry
      information on membrane-associating molecules; it has been used here to scale and
      separate anisotropic contributions to phosphorus chemical shifts in NMR spectra
      of phosphatidylinositol phosphates. The procedure allows spectral assignment via
      correlation with isotropic chemical shifts and determination of a family of
      probable headgroup orientations via interpretation of anisotropic shift
      contributions. The molecules studied include phosphtidylinositol-4-phosphate
      (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). A membrane-like
      environment is provided by a dispersion of alkyl-poly(ethylene) glycols and n
      alcohols that forms a field-orienting liquid crystal with a director that can be
      manipulated by varying the sample spinning axis. The experiments presented
      indicate that the variable angle sample spinning method will provide a direct
      approach for assignment and extraction of structural information from membrane
      associating biomolecules labeled with a wider variety of NMR active isotopes.

PMID- 14645075
TI  - Excessive counterion condensation on immobilized ssDNA in solutions of high ionic
      strength.
AB  - We present experiments on the bias-induced release of immobilized, single
      stranded (ss) 24-mer oligonucleotides from Au-surfaces into electrolyte solutions
      of varying ionic strength. Desorption is evidenced by fluorescence measurements
      of dye-labeled ssDNA. Electrostatic interactions between adsorbed ssDNA and the
      Au-surface are investigated with respect to 1), a variation of the bias potential
      applied to the Au-electrode; and 2), the screening effect of the electrolyte
      solution. For the latter, the concentration of monovalent salt in solution is
      varied from 3 to 1600 mM. We find that the strength of electric interaction is
      predominantly determined by the effective charge of the ssDNA itself and that the
      release of DNA mainly occurs before the electrochemical double layer has been
      established at the electrolyte/Au interface. In agreement with Manning's
      condensation theory, the measured desorption efficiency (etarel) stays constant
      over a wide range of salt concentrations; however, as the Debye length is reduced
      below a value comparable to the axial charge spacing of the DNA, etarel decreases
      substantially. We assign this effect to excessive counterion condensation on the
      DNA in solutions of high ionic strength. In addition, the relative translational
      diffusion coefficient of ssDNA in solution is evaluated for different salt
      concentrations.

PMID- 14645076
TI  - DNA mediated resonance energy transfer from 4',6-diamidino-2-phenylindole to
      [Ru(1,10-phenanthroline)2L]2+.
AB  - The binding site of Delta- and Lambda-[Ru(phenanthroline)2L]2+ (L being
      phenanthroline (phen), dipyrido[3,2-a:2'3'-c]phenazine (DPPZ), and
      benzodipyrido[3,2-a:2'3'-c]phenazine (benzoDPPZ)), bound to poly[d(A-T)2] in the
      presence and absence of 4',6-diamidino-2-phenylindole (DAPI) was investigated by
      circular dichroism and fluorescence techniques. DAPI binds at the minor groove of
      poly[d(A-T)2] and blocks the groove. The circular dichroism spectrum of all
      Ru(II) complexes are essentially unaffected whether the minor groove of poly[d(A
      T)2] is blocked by DAPI or not, indicating that the Ru(II) complexes are
      intercalated from the major groove. When DAPI and Ru(II) complexes simultaneously
      bound to poly[d(A-T)2], the fluorescence intensity of DAPI decreases upon
      increasing Ru(II) complex concentrations. The energy of DAPI at excited state
      transfers to Ru(II) complexes across the DNA via the Forster type resonance
      energy transfer. The efficiency of the energy transfer is similar for both
      [Ru(phen)2DPPZ]2+ and [Ru(phen)2benzoDPPZ]2+ complexes, whereas that of
      [Ru(phen)3]2+ is significantly lower. The distance between DAPI and [Ru(phen)3]2+
      is estimated as 0.38 and 0.64 Forster distance, respectively, for the Delta- and
      Lambda-isomer.

PMID- 14645077
TI  - Bridging the gap between structural and lattice models: a parameterization of
      energy transfer and trapping in Photosystem I.
AB  - In the absence of an accurate structural model, the excited state dynamics of
      energy-transferring systems are often modeled using lattice models. To
      demonstrate the validity and other potential merits of such an approach we
      present the results of the modeling of the energy transfer and trapping in
      Photosystem I based upon the 2.5 A structural model, and show that these results
      can be reproduced in terms of a lattice model with only a few parameters. It has
      recently been shown that at room temperature the dynamics of a hypothetical
      Photosystem I particle, not containing any red chlorophylls (chls), are
      characterized by a longest (trapping) lifetime of 18 ps. The structure-based
      modeling of the dynamics of this particle yields an almost linear relationship
      between the possible values of the intrinsic charge-separation time at P700,
      1/gamma, and the average single-site lifetime in the antenna, tauss. Lattice
      based modeling, using the approach of a perturbed two-level model, reproduces
      this linear relation between tauss and 1/gamma. Moreover, this approach results
      in a value of the (modified) structure-function corresponding to a structure
      exhibiting a mixture of the characteristics of both a square and a cubic lattice,
      consistent with the structural model. These findings demonstrate that the lattice
      model describes the dynamics of the system appropriately. In the lattice model,
      the total trapping time is the sum of the delivery time to the reaction center
      and the time needed to quench the excitation after delivery. For the literature
      value of tauss=150 fs, both these times contribute almost equally to the total
      trapping time of 18 ps, indicating that the system is neither transfer- nor trap
      limited. The value of approximately 9 ps for the delivery time is basically equal
      to the excitation-transfer time from the bulk chls to the red chls in
      Synechococcus elongatus, indicating that energy transfer from the bulk to the
      reaction center and to the red chls are competing processes. These results are
      consistent with low-temperature time-resolved and steady-state fluorescence
      measurements. We conclude that lattice models can be used to describe the global
      energy-transfer properties in complex chromophore networks, with the advantage
      that such models deal with only a few global, intuitive parameters rather than
      the many microscopic parameters obtained in structure-based modeling.

PMID- 14645078
TI  - Excitation wavelength dependence of the fluorescence kinetics in Photosystem I
      particles from Synechocystis PCC 6803 and Synechococcus elongatus.
AB  - The excitation-wavelength dependence of the excited-state dynamics of monomeric
      and trimeric Photosystem I (PSI) particles from Synechocystis PCC 6803 as well as
      trimeric PSI particles from Synechococcus elongatus has been studied at room
      temperature using time-resolved fluorescence spectroscopy. For aselective (400
      nm), carotenoid (505 nm), and bulk chlorophyll (approximately 650 nm) excitation
      in all species, a downhill energy-transfer component is observed, corresponding
      to a lifetime of 3.4-5.5 ps. For selective red excitation (702-719 nm) in all
      species, a significantly faster, an approximately 1-ps, uphill transfer component
      was recorded. In Synechococcus PSI, an additional approximately 10-ps downhill
      energy-transfer component is found for all wavelengths of excitation, except 719
      nm. Each of the species exhibits its own characteristic trap spectrum, the shape
      of which is independent of the wavelength of excitation. This trap spectrum
      decays in approximately 23 ps in both monomeric and trimeric Synechocystis PSI
      and in approximately 35 ps in trimeric Synechococcus PSI. The data were simulated
      based on the 2.5 A structural model of PSI of Synechococcus elongatus using the
      Forster equation for energy transfer, and using the 0.6-1-ps charge-separation
      time and the value of 1.2-1.3 for the index of refraction that were obtained from
      the dynamics of a hypothetical PSI particle without red chls. The experimentally
      obtained lifetimes and spectra were reproduced well by assigning three of the
      chlorophyll-a (chla) dimers observed in the structure to the C708/C702RT pool of
      red chls present in PSI from both species. Essential for the simulation of the
      dynamics of Synechococcus PSI is the assignment of the single chla trimer in the
      structure to the C719/C708RT pool present in this species.

PMID- 14645079
TI  - Ultrafast transient absorption studies on Photosystem I reaction centers from
      Chlamydomonas reinhardtii. 1. A new interpretation of the energy trapping and
      early electron transfer steps in Photosystem I.
AB  - The energy transfer and charge separation kinetics in core Photosystem I (PSI)
      particles of Chlamydomonas reinhardtii has been studied using ultrafast transient
      absorption in the femtosecond-to-nanosecond time range. Although the energy
      transfer processes in the antenna are found to be generally in good agreement
      with previous interpretations, we present evidence that the interpretation of the
      energy trapping and electron transfer processes in terms of both kinetics and
      mechanisms has to be revised substantially as compared to current interpretations
      in the literature. We resolved for the first time i), the transient difference
      spectrum for the excited reaction center state, and ii), the formation and decay
      of the primary radical pair and its intermediate spectrum directly from
      measurements on open PSI reaction centers. It is shown that the dominant energy
      trapping lifetime due to charge separation is only 6-9 ps, i.e., by a factor of 3
      shorter than assumed so far. The spectrum of the first radical pair shows the
      expected strong bleaching band at 680 nm which decays again in the next electron
      transfer step. We show furthermore that the early electron transfer processes up
      to approximately 100 ps are more complex than assumed so far. Several
      possibilities are discussed for the intermediate redox states and their sequence
      which involve oxidation of P700 in the first electron transfer step, as assumed
      so far, or only in the second electron transfer step, which would represent a
      fundamental change from the presently assumed mechanism. To explain the data we
      favor the inclusion of an additional redox state in the electron transfer scheme.
      Thus we distinguish three different redox intermediates on the timescale up to
      100 ps. At this level no final conclusion as to the exact mechanism and the
      nature of the intermediates can be drawn, however. From comparison of our data
      with fluorescence kinetics in the literature we also propose a reversible first
      charge separation step which has been excluded so far for open PSI reaction
      centers. For the first time an ultrafast 150-fs equilibration process, occurring
      among exciton states in the reaction center proper, upon direct excitation of the
      reaction center at 700 nm, has been resolved. Taken together the data call for a
      fundamental revision of the present understanding of the energy trapping and
      early electron transfer kinetics in the PSI reaction center. Due to the fact that
      it shows the fastest trapping time observed so far of any intact PSI particle,
      the PSI core of C. reinhardtii seems to be best suited to further characterize
      the electron transfer steps and mechanisms in the reaction center of PSI.

PMID- 14645080
TI  - Excited state trapping and the Stepanov relation with reference to Photosystem I.
AB  - It has been previously demonstrated that the Stepanov equation provides a rather
      good description of the absorption/fluorescence spectra in Photosystem I, even
      though excited state equilibration is not rapid with respect to the excited state
      decay. In the present article this apparent contradiction is examined
      analytically for two-state systems and numerically for many-state systems. It is
      demonstrated that, in the special case of the trapping process being associated
      with the initially populated state, neither very rapid excited state
      equilibration nor a transfer equilibrium, which approximates a true Boltzmann
      distribution, are prerequisites to obtaining a very close approximation to a
      correct Stepanov result. This interesting conclusion is discussed in terms of
      plant Photosystem I (PSI-200). It is concluded that whereas, in compartmental
      modeling, photochemical trapping may be formally associated with the bulk antenna
      pigments due to the strong energy coupling between them and the trap pigments,
      this is not the case for the red spectral forms.

PMID- 14645081
TI  - Ultrasonic studies of alcohol-induced transconformation in beta-lactoglobulin:
      the intermediate state.
AB  - In mixed alcohol-water solvents, bovine beta-lactoglobulin undergoes a
      cooperative transition from beta-sheet to a high alpha-helix content conformer.
      We report here the characterization of beta-lactoglobulin by compressibility and
      spectroscopy measurements during this transconformation. Both the volume and
      compressibility increase as a function of alcohol concentration, up to maximal
      values which depend on the chemical nature of the three alcohols used:
      hexafluoroisopropanol, trifluoroethanol, and isopropanol. The order of
      effectiveness of alcohols in inducing the compressibility transition is identical
      to that previously reported for circular dichroism and thus independent of the
      observation technique. The highly cooperative sigmoidal curves found by
      compressibility determination match closely those obtained by circular dichroism
      at 222 nm, indicating a correlation between the two phenomena measured by the two
      different techniques. The presence of an equilibrium intermediate form was shown
      by the interaction of beta-lactoglobulin with 8-anilino-1-naphthalene sulfonic
      acid, a probe widely used to detect molten-globule states of proteins. It was
      correlated with the plateau region of the volume curves and with the inflexion
      points of the sigmoidal compressibility curves. Ultrasound characterization of
      proteins can be carried out in optically transparent or nontransparent media.

PMID- 14645082
TI  - Thermodynamics of the hydrophobicity in crystallization of insulin.
AB  - For insight into the solvent structure around protein molecules and its role in
      phase transformations, we investigate the thermodynamics of crystallization of
      the rhombohedral form of porcine insulin crystals. We determine the temperature
      dependence of the solubility at varying concentration of the co-solvent acetone,
      Cac=0%, 5%, 10%, 15%, and 20%, and find that, as a rule, the solubility of
      insulin increases as temperature increases. The enthalpy of crystallization,
      undergoes a stepwise shift from approximately -20 kJ mol(-1) at Cac=0%, 5%, and
      10% to approximately -55 kJ mol(-1) at Cac=15% and 20%. The entropy change upon
      crystallization is approximately 35 J mol(-1) K(-1) for the first three acetone
      concentrations, and drops to approximately -110 J mol(-1) K(-1) at Cac=15% and
      20%. DeltaS degrees cryst>0 indicates release of solvent, mostly water, molecules
      structured around the hydrophobic patches on the insulin molecules' surface in
      the solution. As Cac increases to 15% and above, unstructured acetone molecules
      apparently displace the waters and their contribution to DeltaS degrees cryst is
      minimal. This shifts DeltaS degrees cryst to a negative value close to the value
      expected for tying up of one insulin molecule from the solution. The accompanying
      increase in DeltaH degrees cryst suggests that the water structured around the
      hydrophobic surface moieties has a minimal enthalpy effect, likely due to the
      small size of these moieties. These findings provide values of the parameters
      needed to better control insulin crystallization, elucidate the role of organic
      additives in the crystallization of proteins, and help us to understand the
      thermodynamics of the hydrophobicity of protein molecules and other large
      molecules.

PMID- 14645083
TI  - The glass transition behavior of the globular protein bovine serum albumin.
AB  - The glass-like transition behavior of concentrated aqueous solutions of bovine
      serum albumin was examined using rheological techniques. At mass fractions >0.4,
      there was a marked concentration dependence of viscosity with a glass-like
      kinetic arrest observed at mass fractions in the region of 0.55. At mass
      fractions >0.6 the material behaved as a solid with a Young's modulus rising from
      approximately 20 MPa at a mass fraction of 0.62-1.1 GPa at 0.86. The solid was
      viscoelastic and exhibited stress relaxation with relaxation times increasing
      from 33 to 610 s over the same concentration range. The concentration dependence
      of the osmotic pressure was measured, at intermediate concentrations, using an
      osmotic stress technique and could be described using a hard sphere model,
      indicating that the intermolecular interactions were predominantly repulsive. In
      summary, a major structural relaxation results from the collective motion of the
      globules at the supra-globule length scale and, at 20 degrees C, this is arrested
      at water contents of 40% w/w. This appears to be analogous to the glass
      transition in colloidal hard spheres.

PMID- 14645084
TI  - FRET detection of cellular alpha4-integrin conformational activation.
AB  - Integrins are cell adhesion receptors, expressed on every cell type, that have
      been postulated to undergo conformational changes upon activation. Here,
      different affinity states were generated by exposing alpha4-integrins to divalent
      ions or by inside-out activation using a chemokine receptor. We probed the
      dynamic structural transformation of the integrin on live cells using
      fluorescence resonance energy transfer (FRET) between a peptide donor, which
      specifically binds to the alpha4-integrin, and octadecyl rhodamine B acceptors
      incorporated into the plasma membrane. We analyzed the data using a model that
      describes FRET between a random distribution of donors and acceptors in an
      infinite plane. The distance of closest approach was found to vary with the
      affinity of the integrin. The change in distance of closest approach was
      approximately 50 A between resting and Mn2+ activated receptors and approximately
      25 A after chemokine activation. We used confocal microscopy to probe the lateral
      organization of donors and acceptors subsequent to integrin activation. Taken
      together, FRET and confocal results suggest that changes in FRET efficiencies are
      primarily due to the vertical extension of the integrin. The coordination between
      the extension of alpha4-integrin and its affinity provides a mechanism for
      Dembo's catch-bond concept.

PMID- 14645085
TI  - Configurational temperature density of states simulations of proteins.
AB  - A novel method has been implemented to compute the density of states of proteins.
      A united atom representation and the CHARMM (Brooks et al., 1983) force-field
      parameters have been adopted for all the simulations. In this approach, an
      intrinsic temperature is computed based on configurational information about the
      protein. A random walk is performed in potential energy space and the
      configurational temperature is collected as a function of potential energy of the
      system. The density of states is then calculated by integrating the reciprocal of
      temperature. Unlike previously available methods, this approach does not involve
      calculations based on histograms of stochastic visits to distinct energy states.
      It is found that the proposed method is more efficient than earlier, related
      schemes for simulation of protein folding. Furthermore, it directly provides
      thermodynamic information, including free energies. The usefulness of the method
      is discussed by presenting results of simulations of the 16-residue beta-hairpin
      taken from the C-terminal fragment (41-56) of protein G.

PMID- 14645086
TI  - Lipoplex thermodynamics: determination of DNA-cationic lipoid interaction
      energies.
AB  - An experimental study of the cationic lipid-DNA binding affinity is presented.
      The binding free energy was determined by monitoring lipoplex dissociation under
      conditions of increasing salt concentration. The primary procedure was based on
      the extent of quenching by energy transfer of fluorophores on DNA molecules by
      fluorophore on a lipid as these molecules came into close association in the
      lipoplex. Titration calorimetry on the Dickerson dodecamer was also done, with
      results that were in agreement with the fluorescence data. Measurements on short
      oligonucleotides allowed estimation of the binding energy per nucleotide. The
      binding free energy is approximately 0.6 kcal/mole nucleotide for the Dickerson
      dodecamer and declines for longer oligonucleotides. The entropy gained upon
      complex formation is approximately 1 entropy unit per released counterion. The
      method was applied to long DNA molecules (herring and lambda-phage DNA) and
      revealed that complete dissociation occurs at 750 mM NaCl. Likely contributions
      of macromolecular desolvation and DNA flexibility to the binding energy are
      discussed.

PMID- 14645087
TI  - The circularization of amyloid fibrils formed by apolipoprotein C-II.
AB  - Amyloid fibrils have historically been characterized by diagnostic dye-binding
      assays, their fibrillar morphology, and a "cross-beta" x-ray diffraction pattern.
      Whereas the latter demonstrates that amyloid fibrils have a common beta-sheet
      core structure, they display a substantial degree of morphological variation. One
      striking example is the remarkable ability of human apolipoprotein C-II amyloid
      fibrils to circularize and form closed rings. Here we explore in detail the
      structure of apoC-II amyloid fibrils using electron microscopy, atomic force
      microscopy, and x-ray diffraction studies. Our results suggest a model for apoC
      II fibrils as ribbons approximately 2.1-nm thick and 13-nm wide with a helical
      repeat distance of 53 nm +/- 12 nm. We propose that the ribbons are highly
      flexible with a persistence length of 36 nm. We use these observed biophysical
      properties to model the apoC-II amyloid fibrils either as wormlike chains or
      using a random-walk approach, and confirm that the probability of ring formation
      is critically dependent on the fibril flexibility. More generally, the ability of
      apoC-II fibrils to form rings also highlights the degree to which the common
      cross-beta superstructure can, as a function of the protein constituent, give
      rise to great variation in the physical properties of amyloid fibrils.

PMID- 14645088
TI  - Image-adaptive deconvolution for three-dimensional deep biological imaging.
AB  - Deconvolution algorithms are widely used in conventional fluorescence microscopy,
      but they remain difficult to apply to deep imaging systems such as confocal and
      two-photon microscopy, due to the practical difficulty of measuring the system's
      point spread function (PSF), especially in biological experiments. Since a
      separate PSF measurement performed under the design optical conditions of the
      microscope cannot reproduce the true experimental conditions prevailing in situ,
      the most natural approach to solve the problem is to extract the PSF from the
      images themselves. We investigate here the approach of cropping an approximate
      PSF directly from the images, by exploiting the presence of small structures
      within the samples under study. This approach turns out to be practical in many
      cases, allowing significantly better restorations than with a design PSF obtained
      by imaging fluorescent beads in gel. We demonstrate the advantages of this
      approach with a number of deconvolution experiments performed both on
      artificially blurred and noisy test images, and on real confocal images taken
      within an in vitro preparation of the mouse hearing organ.

PMID- 14645089
TI  - Three-dimensional structure of the mammalian tachykinin peptide neurokinin A
      bound to lipid micelles.
AB  - The solution structure of NKA, a decapeptide of mammalian origin, has been
      characterized by CD spectropolarimetry and 2D proton nuclear magnetic resonance
      (2D 1H-NMR) spectroscopy in both aqueous and membrane mimetic solvents.
      Unambiguous NMR assignments of protons have been made with the aid of correlation
      spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect
      spectroscopy (NOESY and ROESY) experiments. The distance constraints obtained
      from the NMR data have been utilized to generate a family of structures, which
      have been refined using restrained energy minimization and dynamics. These data
      show that in water NKA prefers to be in an extended chain conformation whereas a
      helical conformation is induced in the central core and the C-terminal region (D4
      M10) of the peptide in the presence of perdeuterated dodecylphosphocholine (DPC)
      micelles, a membrane model system. Though less defined the N-terminus also
      displays some degree of order and a possible turn structure. The conformation
      adopted by NKA in the presence of DPC micelles represents a structural motif
      typical of neurokinin-2 selective agonists and is similar to that reported for
      eledoisin in hydrophobic environment.

PMID- 14645090
TI  - Conformation of reconstituted mononucleosomes and effect of linker histone H1
      binding studied by scanning force microscopy.
AB  - The conformation of mononucleosome complexes reconstituted with recombinant core
      histones on a 614-basepair-long DNA fragment containing the Xenopus borealis 5S
      rRNA nucleosome positioning sequence was studied by scanning/atomic force
      microscopy in the absence or presence of linker histone H1. Imaging without prior
      fixation was conducted with air-dried samples and with mononucleosomes that were
      injected directly into the scanning force microscopy fluid cell and visualized in
      buffer. From a quantitative analysis of approximately 1,700 complexes, the
      following results were obtained: i), In the absence of H1, a preferred location
      of the nucleosome at the X. borealis 5S rRNA sequence in the center of the DNA
      was detected. From the distribution of nucleosome positions, an energy difference
      of binding to the 5S rRNA sequence of DeltaDeltaG approximately 3 kcal mol(-1) as
      compared to a random sequence was estimated. Upon addition of H1, a significantly
      reduced preference of nucleosome binding to this sequence was observed. ii), The
      measured entry-exit angles of the DNA at the nucleosome in the absence of H1
      showed two maxima at 81 +/- 29 degrees and 136 +/- 18 degrees (air-dried
      samples), and 78 +/- 25 degrees and 137 +/- 25 degrees (samples imaged in buffer
      solution). In the presence of H1, the species with the smaller entry-exit angle
      was stabilized, yielding average values of 88 +/- 34 degrees for complexes in air
      and 85 +/- 10 degrees in buffer solution. iii), The apparent contour length of
      the nucleosome complexes was shortened by 34 +/- 13 nm as compared to the free
      DNA due to wrapping of the DNA around the histone octamer complex. Considering an
      11 nm diameter of the nucleosome core complex, this corresponds to a total of 145
      +/- 34 basepairs that are wound around the nucleosome.

PMID- 14645091
TI  - Hydration, structure, and molecular interactions in the headgroup region of
      dioleoylphosphatidylcholine bilayers: an electron spin resonance study.
AB  - The relationship between bilayer hydration and the dynamic structure of
      headgroups and interbilayer water in multilamellar vesicles is investigated by
      electron spin resonance methods. Temperature variations of the order parameter of
      a headgroup spin label DPP-Tempo in DOPC in excess water and partially dehydrated
      (10 wt % water) show a cusp-like pattern around the main phase transition, Tc.
      This pattern is similar to those of temperature variations of the quadrupolar
      splitting of interbilayer D2O in PC and PE bilayers previously measured by 2H
      NMR, indicating that the ordering of the headgroup and the interbilayer water are
      correlated. The cusp-like pattern of these and other physical properties around
      Tc are suggestive of quasicritical fluctuations. Also, an increase (a decrease)
      in ordering of DPP-Tempo is correlated with water moving out of (into)
      interbilayer region into (from) the bulk water phase near the freezing point, Tf.
      Addition of cholesterol lowers Tf, which remains the point of increasing
      headgroup ordering. Using the small water-soluble spin probe 4-PT, it is shown
      that the ordering of interbilayer water increases with bilayer dehydration. It is
      suggested that increased ordering in the interbilayer region, implying a lowering
      of entropy, will itself lead to further dehydration of the interbilayer region
      until its lowered pressure resists further flow, i.e., an osmotic phenomenon.

PMID- 14645092
TI  - Fractal dimension in human cerebellum measured by magnetic resonance imaging.
AB  - Fractal dimension has been used to quantify the structures of a wide range of
      objects in biology and medicine. We measured fractal dimension of human
      cerebellum (CB) in magnetic resonance images of 24 healthy young subjects (12 men
      and 12 women). CB images were resampled to a series of image sets with different
      3D resolutions. At each resolution, the skeleton of the CB white matter was
      obtained and the number of pixels belonging to the skeleton was determined.
      Fractal dimension of the CB skeleton was calculated using the box-counting
      method. The results indicated that the CB skeleton is a highly fractal structure,
      with a fractal dimension of 2.57 +/- 0.01. No significant difference in the CB
      fractal dimension was observed between men and women.

PMID- 14645093
TI  - Single-crystal EPR study at 95 GHz of the type 2 copper site of the inhibitor
      bound quercetin 2,3-dioxygenase.
AB  - An electron-spin-echo-detected, electron-paramagnetic-resonance study has been
      performed on the type 2 copper site of quercetin 2,3-dioxygenase from Aspergillus
      japonicus. In the protein, copper is coordinated by three histidine nitrogens and
      two sulfurs from the inhibitor diethyldithiocarbamate. A single crystal of the
      protein was studied at 95 GHz and the complete g-tensor determined. The electron
      paramagnetic-resonance data are compatible with two orientations of the principal
      g-axes in the copper center, one of which is preferred on the basis of an
      analysis of the copper coordination and the d-orbitals that are involved in the
      unpaired-electron orbital. For this orientation, the principal z-axis of the g
      tensor makes an angle of 19 degrees with the Cu-N(His112) bond and the N of
      His112 may be considered the axial ligand. The singly occupied molecular orbital
      contains a linear combination of copper dxy and dyz-orbitals, which are
      antibonding with atomic orbitals of histidine nitrogens and
      diethyldithiocarbamate sulfurs. The orientation of the g-tensor for the quercetin
      2,3-dioxygenase is compared with that for type 1 copper sites.

PMID- 14645094
TI  - Electrochemical and photon polarization modulation infrared reflection absorption
      spectroscopy study of the electric field driven transformations of a phospholipid
      bilayer supported at a gold electrode surface.
AB  - Electrochemistry and polarization modulation Fourier transform infrared
      reflection absorption spectroscopy (PM-FTIRRAS) was employed to investigate
      fusion of small unilamellar vesicles of 1,2dioyl-sn-glycero-3-phosphatidyl
      choline (DOPC) onto the Au(111) electrode. Electrochemical studies demonstrated
      that the DOPC vesicles fuse and spread onto the gold electrode surface at small
      charge densities -8 microC cm(-2)<sigmaM<0 microC cm(-2)(if the static electric
      field is <2 x 10(8) V/m) to form a bilayer. At sigmaM<-8 microC cm(-2), the film
      is detached from the electrode surface; however, the film remains in close
      proximity to the surface. The PM-FTIRRAS experiments demonstrated that the field
      driven transformation of the film involves changes in hydration, orientation, and
      conformation in the polar headgroup region and that changes in the packing and
      tilt of the acyl chains are consequences of the headgroup rearrangements.

PMID- 14645095
TI  - The cell wall of lactic acid bacteria: surface constituents and macromolecular
      conformations.
AB  - A variety of strains of the genus Lactobacillus was investigated with respect to
      the structure, softness, and interactions of their outer surface layers in order
      to construct structure-property relations of the Gram-positive bacterial cell
      wall. The role of the conformational properties of the constituents of the outer
      cell-wall layers and their spatial distribution on the cell wall is emphasized.
      Atomic force microscopy was used to resolve the surface structure, interactions,
      and softness of the bacterial cell wall at nanometer-length scales and upwards.
      The pH-dependence of the electrophoretic mobility and a novel interfacial
      adhesion assay were used to analyze the average physicochemical properties of the
      bacterial strains. The bacterial surface is smooth when a compact layer of
      globular proteins constitutes the outer surface, e.g., the S-layer of L.
      crispatus DSM20584. In contrast, for two other S-layer containing strains (L.
      helveticus ATCC12046 and L. helveticus ATCC15009), the S-layer is covered by
      polymeric surface constituents which adopt a much more extended conformation and
      which confer a certain roughness to the surface. Consequently, the S-layer is
      important for the overall surface properties of L. crispatus, but not for the
      surface properties of L. helveticus. Both surface proteins (L. crispatus
      DSM20584) and (lipo)teichoic acids (L. johnsonii ATCC332) confer hydrophobic
      properties to the bacterial surface whereas polysaccharides (L. johnsonii
      DSM20533 and L. johnsonii ATCC 33200) render the bacterial surface hydrophilic.
      Using the interfacial adhesion assay, it was demonstrated that hydrophobic groups
      within the cell wall adsorb limited quantities of hydrophobic compounds. The
      present work demonstrates that the impressive variation in surface properties
      displayed by even a limited number of genetically-related bacterial strains can
      be understood in terms of established colloidal concepts, provided that
      sufficiently detailed structural, chemical, and conformational information on the
      surface constituents is available.

PMID- 14645096
TI  - Quantitative topographical analysis of nuclear pore complex function using
      scanning force microscopy.
AB  - The only avenue for macromolecular communication between nucleoplasmic and
      cytoplasmic compartments of the cell is through the nuclear pore complexes
      (NPCs), which are thus situated at a key location for the control of downstream
      transcriptional processes. The translocation of cargo through the NPC is mediated
      by transport receptors, which have the difficult task of making specific, yet
      transitory, interactions with the NPC in order to support efficient transport. In
      this report we have examined two stages in the translocation process using
      scanning force microscopy. We show that the initial docking of importin beta 45
      462 is rapid and occurs at nanomolar concentrations. Later stages of transport
      involve translocation through the central lumen of the NPC and are thought to
      involve hydrophobic interactions between transport receptors and the NPC. Using
      calcium-depleted nuclear envelopes we argue that luminal regions of the NPC
      exhibit hydrophobic characteristics that are not observed for other regions of
      the NPC.

PMID- 14645097
TI  - Kinetics of GPIbalpha-vWF-A1 tether bond under flow: effect of GPIbalpha
      mutations on the association and dissociation rates.
AB  - The interaction between platelet glycoprotein (GP) Ib-IX-V complex and von
      Willebrand factor (vWF) is the first step of the hemostatic response to vessel
      injury. In platelet-type von Willebrand disease, two mutations, G233V and M239V,
      have been described within the Cys209-Cys248 disulfide loop of GPIbalpha that
      compromise hemostasis by increasing the affinity for vWF. We have earlier shown
      that converting other residues in this region to valine alters the affinity of
      GPIbalpha for vWF, with mutations K237V and Q232V, respectively, showing the
      greatest increase and decrease in affinity. Here, we investigated further the
      effect of these two mutations on the kinetics of the GPIbalpha interaction with
      the vWF-A1 domain under dynamic flow conditions. We measured the cellular on- and
      off-rate constants of Chinese hamster ovary cells expressing GPIb-IX complexes
      containing wild-type or mutant GPIbalpha interacting with vWF-A1-coated surfaces
      at different shear stresses. We found that the gain-of-function mutant, K237V,
      rolled very slowly and continuously on vWF-A1 surface while the loss-of-function
      mutant, Q232V, showed fast, saltatory movement compared to the wild-type (WT).
      The off-rate constants, calculated based on the analysis of lifetimes of
      transient tethers formed on surfaces coated with limiting densities of vWF-A1,
      revealed that the Q232V and K237V dissociated 1.25-fold faster and 2.2-fold
      slower than the WT. The cellular on-rate constant of WT, measured in terms of
      tethering frequency, was threefold more and threefold less than Q232V and K237V,
      respectively. Thus, the gain- and loss-of-function mutations in GPIbalpha affect
      both the association and dissociation kinetics of the GPIbalpha-vWF-A1 bond.
      These findings are in contrast to the functionally similar selectin bonds where
      some of the mutations have been reported to affect only the dissociation rate.

PMID- 14645098
TI  - Detecting and quantifying colocalization of cell surface molecules by single
      particle fluorescence imaging.
AB  - Single particle fluorescence imaging (SPFI) uses the high sensitivity of
      fluorescence to visualize individual molecules that have been selectively labeled
      with small fluorescent particles. The positions of particles are determined by
      fitting the intensity profile of their images to a 2-D Gaussian function. We have
      exploited the positional information obtained from SPFI to develop a method for
      detecting colocalization of cell surface molecules. This involves labeling two
      different molecules with different colored fluorophores and determining their
      positions separately by dual wavelength imaging. The images are analyzed to
      quantify the overlap of the particle images and hence determine the extent of
      colocalization of the labeled molecules. Simulated images and experiments with a
      model system are used to investigate the extent to which colocalization occurs
      from chance proximity of randomly distributed molecules. A method of correcting
      for positional shifts that result from chromatic aberration is presented. The
      technique provides quantification of the extent of colocalization and can detect
      whether colocalized molecules occur singly or in clusters. We have obtained
      preliminary data for colocalization of molecules on intact cells. Cells often
      exhibit particulate autofluorescence that can interfere with the measurements; a
      method for overcoming this problem by triple wavelength imaging is described.

PMID- 14645099
TI  - Avidity modulation activates adhesion under flow and requires cooperativity among
      adhesion receptors.
AB  - An early step in activation of leukocyte adhesion is a release of integrins from
      cytoskeletal constraints on their diffusion, leading to rearrangement and,
      consequently, increased avidity. Static adhesion assays using purified ligand as
      a substrate have demonstrated that very low doses of cytochalasin D disconnect
      beta2-integrins from their cytoskeletal links, allowing rearrangement and
      activating adhesion. The adhesion process in blood vessels is poorly simulated by
      these assays, however, for two reasons: leukocyte adhesion to endothelium 1),
      occurs in the presence of blood flow and 2), involves the simultaneous
      interactions of multiple sets of adhesion molecules. We investigated the effect
      of cytochalasin D, at concentrations that increase integrin diffusion but do not
      alter leukocyte shape and surface features, on adhesion of leukocytes to
      endothelial cells under flow. Cytochalasin D increased the number of rolling
      cells, the number of firmly adherent cells, and the duration of both rolling and
      firm adhesion. These effects required endothelial cell expression of ICAM-1, the
      ligand for leukocyte beta2-integrins. The beta2-integrin-ICAM-1 interaction alone
      was not sufficient, however. Experiments using purified substrates demonstrated
      that avidity effects on activation of adhesion under flow require functional
      cooperativity between integrins and other adhesion receptors.

PMID- 14645100
TI  - Examination of optical depth effects on fluorescence imaging of cardiac
      propagation.
AB  - Optical mapping with voltage-sensitive dyes provides a high-resolution technique
      to observe cardiac electrodynamic behavior. Although most studies assume that the
      fluorescent signal is emitted from the surface layer of cells, the effects of
      signal attenuation with depth on signal interpretation are still unclear. This
      simulation study examines the effects of a depth-weighted signal on epicardial
      activation patterns and filament localization. We simulated filament behavior
      using a detailed cardiac model, and compared the signal obtained from the top
      (epicardial) layer of the spatial domain with the calculated weighted signal.
      General observations included a prolongation of the action upstroke duration,
      early upstroke initiation, and reduction in signal amplitude in the weighted
      signal. A shallow filament was found to produce a dual-humped action potential
      morphology consistent with previously reported observations. Simulated scroll
      wave breakup exhibited effects such as the false appearance of graded potentials,
      apparent supramaximal conduction velocities, and a spatially blurred signal with
      the local amplitude dependent upon the immediate subepicardial activity; the
      combination of these effects produced a corresponding change in the accuracy of
      filament localization. Our results indicate that the depth-dependent optical
      signal has significant consequences on the interpretation of epicardial
      activation dynamics.

PMID- 14645101
TI  - On the role of H-NS in the organization of bacterial chromatin: from bulk to
      single molecules and back.

PMID- 14645102
TI  - Chemosensory stimulation of luteinizing hormone secretion in male Siberian
      hamsters (Phodopus sungorus).
AB  - Male Siberian hamsters (Phodopus sungorus) housed in long days (LD), but not
      short days (SD) release luteinizing hormone (LH) when exposed to females. This
      study examined whether this response is specific to a female and identifies the
      source of a stimulus that induces LH release. Serum concentrations of LH,
      testosterone (T), follicle stimulating hormone (FSH), and cortisol were examined
      in all experiments. T concentrations mirrored the LH response; FSH and cortisol
      were unchanged in response to all stimuli. Exposure to an LD female, irrespective
      of her reproductive status, but not an SD female, elicited LH release. Exposure
      to another male did not trigger LH release. Males released LH when allowed
      physical contact with an anesthetized female, but not when separated from a
      normally active female, suggesting that tactile or nonvolatile chemosensory
      stimuli elicit LH release. Urine and secretions collected from the vagina as well
      as oral, midventral, perineal, and rectal glands, elicited marked behavioral
      responses in male P. sungorus. Despite these behavioral responses, only feces
      from females elicited LH release in males. Males released LH in response to feces
      extracted from the rectum and to cotton swabs that had been rubbed against the
      rectal mucosa, suggesting that a component of rectal secretions may trigger LH
      release in male Siberian hamsters. Taken together, these data and previous data
      from our laboratory indicate that both the production of and the response to a
      pheromone that triggers the selective release of LH is regulated by day length.

PMID- 14645103
TI  - Distinction of sperm-binding site and reactive site for trypsin inhibition on p12
      secreted from the accessory sex glands of male mice.
AB  - Six variants of P12, a Kazal-type trypsin inhibitor in the secretion of male
      mouse accessory sexual glands, were made using single-site mutations including
      R19L, Y21V, D22G, R43G, K44S, and R45T, based on one-letter-code mutation of
      amino acids. The other two variants, Nd10 and Cd8, were made using the deletion
      of 10 and 8 residues from the N- and C-terminals, respectively. Their CD profiles
      revealed maintenance of the P12 conformation in the seven variants, excluding
      Cd8, which became unfolded. Only R19L entirely lost the ability while the other
      variants were as strong as P12 in inhibiting the trypsin digestion of N-benzoyl
      Phe-Val-Arg 7-amido-4-methylcoumarin. The immunocytochemical results demonstrated
      that D22G and Cd8 failed to bind to sperm, Y21V very weakly did so, and the other
      variants retained their sperm-binding abilities. Concomitantly, the
      immunocytochemical stainability of each ligand was parallel to its inhibitory
      effect on 125I-P12-sperm binding, and a synthetic oligopeptide corresponding to
      residues 18-24 of P12 was able to inhibit P12-sperm binding. The data together
      concluded that R19 was essential for protease inhibition and D22 and/or Y21
      mainly being responsible for the binding of P12 to sperm. The steric arrangement
      of R19, Y21, and D22 on the tertiary structure of P12 is discussed.

PMID- 14645104
TI  - Molecular modifications of MC31/CE9, a sperm surface molecule, during sperm
      capacitation and the acrosome reaction in the rat: is MC31/CE9 required for
      fertilization?
AB  - We examined the modification of the MC31 molecule during capacitation, the
      acrosome reaction, and studied its role in fertilization. These studies revealed
      that the molecular mass of MC31 in cauda spermatozoa was approximately 28,000
      26,000 Dalton (28-26 kDa). A limited change in molecular mass was seen in
      capacitated spermatozoa. Treatment of sperm extracts with peptide-N-glycosidase
      (PN glycosidase) reduced the molecular mass of MC31 in both cauda and capacitated
      spermatozoa from 28-26 kDa to 23-20 kDa, suggesting that MC31 from both cauda and
      capacitated spermatozoa is glycosylated, and indicating that capacitation induces
      minor posttranslational modifications in the structure of the MC31 antigen. The
      MC31 antigen was redistributed from the midpiece of cauda epididymal spermatozoa
      to the head and equatorial segment after capacitation and acrosome reaction,
      respectively, when traced by indirect immunofluorescence under in vitro
      fertilization (IVF) conditions. Some spermatozoa did not stain for the MC31
      antigen and might represent spermatozoa that have shed the antigen. IVF
      experiments conducted to assess the effect of an anti-MC31 monoclonal antibody
      (mMC31) revealed that this antibody significantly (P < 0.01) inhibited
      fertilization of cumulus-invested zona pellucida-intact and the zona pellucida
      free oocytes in a dose-dependent manner. However, sperm-oolemma binding was not
      affected. These findings suggest the MC31 antigen facilitates sperm-oocyte
      interactions.

PMID- 14645105
TI  - Transient DNA strand breaks during mouse and human spermiogenesis new insights in
      stage specificity and link to chromatin remodeling.
AB  - In the course of mammalian spermiogenesis, a unique chromatin remodeling process
      takes place within elongating and condensing spermatid nuclei. The histone-to
      protamine exchange results in efficient packaging and increased stability of the
      paternal genome. Although not fully understood, this change in chromatin
      architecture must require a global but transient appearance of endogenous DNA
      strand breaks because most of the DNA supercoiling is eliminated in the mature
      sperm. To establish the extent of DNA strand breakage and the stage specificity
      at which these breaks are created and repaired, we performed a sensitive terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay
      to detect in situ DNA strand breaks on both mice and human testis cross sections.
      In the mouse, we established that DNA strand breaks are indeed detected in the
      whole population of elongating spermatids between stages IX and XI of the
      seminiferous epithelium cycle perfectly coincident with the chromatin remodeling
      as revealed by histone H4 hyperacetylation. Similarly, TUNEL analyses performed
      on human testis sections revealed an elevated and global increase in the levels
      of DNA strand breaks present in nuclei of round-shaped spermatids also coincident
      with chromatin remodeling. The demonstration of the global character of the
      transient DNA strand breaks in mammalian spermiogenesis suggests that deleterious
      consequences on genetic integrity of the male gamete may arise from any
      disturbance in the process. In addition, this investigation may shed some light
      on the origin of the low success rate that has been encountered so far with
      intracytoplasmic injection procedures making use of round spermatids in humans.

PMID- 14645106
TI  - Novel tyrosine-phosphorylated post-pyruvate metabolic enzyme, dihydrolipoamide
      dehydrogenase, involved in capacitation of hamster spermatozoa.
AB  - Capacitation is a process that confers fertilizing ability to spermatozoa and
      this critical event occurs in the development of mammalian spermatozoa during
      their transit through the female reproductive tract and precedes fertilization.
      Because spermatozoa are relatively silent in transcription and translation,
      posttranslational modifications perform the regulatory functions in these cells
      during capacitation. In this report, we identify a candidate protein,
      dihydrolipoamide dehydrogenase, which is a post-pyruvate metabolic enzyme,
      exhibiting tyrosine phosphorylation during hamster spermatozoal capacitation.
      This is the first report showing dihydrolipoamide dehydrogenase as a
      phosphoprotein. The cDNA sequence of hamster testes dihydrolipoamide
      dehydrogenase does not show any variation from the already reported mammalian
      dihydrolipoamide dehydrogenases. Downregulation of the activity of the hamster
      spermatozoal enzyme by its specific inhibitor, 5-methoxyindole-2-carboxylic acid,
      blocks acrosome reaction completely and hyperactivation partially, confirming the
      role of dihydrolipoamide dehydrogenase in hamster spermatozoal capacitation. We
      also delineate the temporal involvement of glucose and pyruvate-lactate, showing
      that the former is required in the earlier stages and the latter for the later
      stages of hamster spermatozoal capacitation. The essentiality of pyruvate-lactate
      during hyperactivation and acrosome reaction necessitates the involvement of the
      post-pyruvate-lactate enzyme, dihydrolipoamide dehydrogenase.

PMID- 14645107
TI  - Interactions of proteases, protease inhibitors, and the beta1 integrin/laminin
      gamma3 protein complex in the regulation of ectoplasmic specialization dynamics
      in the rat testis.
AB  - During spermatogenesis, developing germ cells migrate progressively across the
      seminiferous epithelium. This event requires extensive restructuring of cell-cell
      actin-based adherens junctions (AJs), such as the ectoplasmic specialization (ES,
      a testis-specific AJ type), between Sertoli cells and elongating/elongate
      spermatids. It was postulated that proteases and protease inhibitors worked in a
      yin-yang relationship to regulate these events. If this is true, then it is
      anticipated that both proteases and protease inhibitors are found at the ES.
      Indeed, matrix metalloprotease (MMP)-2, membrane-type 1 (MT1)-MMP and their
      inhibitor, tissue-inhibitor of metalloproteases (TIMP)-2, were shown to localize
      at the apical ES. In order to identify the putative MMP substrate as well as the
      unknown binding ligand for alpha6beta1 integrin in the ES, immunofluorescent
      microscopy coupled with immunoprecipitation techniques were used to demonstrate
      that laminin gamma3, largely a germ cell product, was present at the apical ES
      and could form a bona fide complex with beta1-integrin. Furthermore, the
      structural interactions of MMP-2 and MT1-MMP with laminin gamma3 and beta1
      integrin, but not with N-cadherin or nectin-3, have implicated the crucial role
      of MMP-2/MT1-MMP in the regulation of integrin/laminin-based ES dynamics. Using
      an in vivo model to study AJ dynamics where adult rats were treated with 1-(2,4
      dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364) to disrupt Sertoli-germ cell
      adhesive function, an induction of active MMP-2, active MT1-MMP and TIMP-2 but
      not active MMP-9 was detected between 0.5 and 8 h after AF-2364 treatment. This
      time frame coincided with the depletion of elongating/elongate spermatids from
      the epithelium, illustrating the synergistic relationships between MMP-2, MT1
      MMP, and TIMP-2 in AJ disassembly. Perhaps the most important of all, the use of
      a specific MMP-2 and MMP-9 inhibitor, (2R)-2-[(4-biphenylylsulfonyl)amino]-3
      phenylpropionic acid, could effectively delay the AF-2364-induced
      elongating/elongate spermatid loss from the epithelium, demonstrating the pivotal
      role of MMP-2 activation in ES disassembly. Collectively, these studies
      illustrate that the beta1-integrin/laminin gamma3 complex is a putative ES
      structural protein complex, which is regulated, at least in part, by the
      activation of MMP-2 involving MT1-MMP and TIMP-2 at the apical ES. The net result
      of this interaction likely regulates germ cell movement in the seminiferous
      epithelium.

PMID- 14645108
TI  - Alternatively spliced variants of Gallus gallus TNFRSF23 are expressed in the
      ovary and differentially regulated by cell signaling pathways.
AB  - As a result of searching recently available chicken (ch) expressed sequence tag
      databases, a new Tumor Necrosis Factor Receptor Super Family (TNFRSF) member with
      similarity to the murine (m) TNFRSF23 decoy receptor (DcR) has been identified.
      However, by comparison with the mTNFRSF23, there exist at least two splice
      variants of chTNFRSF23, one of which includes an intracellular death domain
      (TNFRSF23.v1) characteristic of death receptors, and the other with a truncated
      cytoplasmic domain of a DcR (named TNFRSF23.v2). These two splice variants of
      chTNFRSF23 display differential patterns of mRNA expression across various hen
      tissues, with the highest levels observed within reproductive tissues. More
      specifically, TNFRSF23.v1 is most highly expressed in preovulatory follicle
      granulosa cells in the ovary, whereas TNFRSF23.v2 mRNA is found at highest levels
      in ovarian stromal tissue. Primary culture experiments with granulosa cells
      determined that expression of TNFRSF23.v1 mRNA was decreased by protein kinase A
      signaling and enhanced by transforming growth factor (TGF) alpha treatment.
      Interestingly, TGFbeta1 and signaling via protein kinase C also enhanced levels
      of TNFRSF23.v1 expression but only in undifferentiated granulosa cells from
      prehierarchal follicles. Based on patterns of mRNA expression and its
      endocrine/paracrine regulation, we predict that ovarian chTNFRSF23 represents a
      modulator of granulosa cell survival and/or differentiation. Finally, the
      characterization of these receptor variants is of considerable interest from an
      evolutionary perspective in that they provide additional evidence to support a
      continuing divergence of TNFRSF members throughout vertebrate evolution.

PMID- 14645109
TI  - Progesterone and gravidity differentially regulate expression of extracellular
      matrix components in the pregnant rat myometrium.
AB  - Myometrial growth and remodeling during pregnancy depends on increased synthesis
      of interstitial matrix proteins. We hypothesize that the presence of mechanical
      tension in a specific hormonal environment regulates the expression of
      extracellular matrix (ECM) components in the uterus. Myometrial tissue was
      collected from pregnant rats on Gestational Days 0, 12, 15, 17, 19, 21, 22, 23
      (labor), and 1 day postpartum and ECM expression was analyzed by Northern
      blotting. Expression of fibronectin, laminin beta2, and collagen IV mRNA was low
      during early gestation but increased dramatically on Day 23 during labor.
      Expression of fibrillar collagens (type I and III) peaked Day 19 and decreased
      near term. In contrast, elastin mRNA remained elevated from midgestation onward.
      Injection of progesterone (P4) on Days 20-23 (to maintain elevated plasma P4
      levels) delayed the onset of labor, caused dramatic reductions in the levels of
      fibronectin and laminin mRNA, and prevented the fall of collagen III mRNA levels
      on Day 23. Treatment of pregnant rats with the progesterone receptor antagonist
      RU486 on Day 19 induced preterm labor on Day 20 and a premature increase in mRNA
      levels of collagen IV, fibronectin, and laminin. Analysis of the uterine tissue
      from unilaterally pregnant rats revealed that most of the changes in ECM gene
      expression occurred specifically in the gravid horn. Our results show a decrease
      in expression of fibrillar collagens and a coordinated temporal increase in
      expression of components of the basement membrane near term associated with
      decreased P4 and increased mechanical tension. These ECM changes contribute to
      myometrial growth and remodeling during late pregnancy and the preparation for
      the synchronized contractions of labor.

PMID- 14645110
TI  - Tamoxifen inhibits cell proliferation via mitogen-activated protein kinase
      cascades in human ovarian cancer cell lines in a manner not dependent on the
      expression of estrogen receptor or the sensitivity to cisplatin.
AB  - Although tamoxifen (TAM), which is widely used in the treatment of breast cancer,
      also has a beneficial effect on cisplatin-refractory ovarian cancer, the
      biological mechanism of this effect has remained obscure. TAM, besides its action
      as an antiestrogen, also inhibits cell proliferation of estrogen receptor (ER)
      negative cells by an unknown mechanism. Therefore, we examined the roles of the
      MAPK family in the antiproliferative effect of TAM on cisplatin-resistant Caov-3,
      which expresses ER and cisplatin-sensitive A2780, which does not express ER. The
      number of viable cells was reduced by TAM dose-dependently. TAM induced the
      activation of ERK, c-Jun N-terminal protein kinase (JNK), and p38 with different
      time courses. PD98059 canceled the reduction of the number of viable cells by 1
      microM TAM and inhibited the TAM-induced cell-cycle arrest at the G(1) phase and
      dephosphorylation of the retinoblastoma protein. Either expression of dominant
      negative JNK or pretreatment with SB203580 canceled the reduction of the number
      of viable cells by 5 microM TAM and inhibited the apoptotic nuclear changes and
      the cleavage of poly (ADP-ribose) polymerase induced by TAM. These results
      provide evidence that whereas the ERK cascade is involved in the induction of
      cell-cycle arrest at the G(1) phase by lower concentrations of TAM, the JNK or
      p38 cascade is involved in the induction of apoptosis by higher concentrations of
      TAM in both types of cells.

PMID- 14645111
TI  - Calcium-sensing receptor induces proliferation through p38 mitogen-activated
      protein kinase and phosphatidylinositol 3-kinase but not extracellularly
      regulated kinase in a model of humoral hypercalcemia of malignancy.
AB  - Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of
      malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related
      peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and
      stress-activated kinases, e.g. MAPK kinase 1 (MEK1), p38 MAPK, and stress
      activated protein kinase 1/c-Jun N-terminal kinase. Because cellular
      proliferation is a hallmark of malignancy, we studied the role of the CaR in
      regulating the proliferation of H-500 cells. Elevated Ca(2+) has a mitogenic
      effect on these cells that is mediated by the CaR, because the calcimimetic NPS R
      467 also induced proliferation. Inhibition of phosphatidylinositol 3-kinase
      (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. Activation of
      PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream
      kinase, protein kinase B. Because protein kinase B activation promotes cell
      survival, we speculated that elevated Ca(2+) might protect H-500 cells against
      apoptosis. Using terminal uridine deoxynucleotidyl nick end labeling staining, we
      demonstrated that high Ca(2+) (7.5 mM) and NPS R-467 indeed protect cells against
      apoptosis induced by serum withdrawal compared with low Ca(2+) (0.5 mM). Because
      the CaR induces PTHrP secretion, it is possible that the mitogenic and
      antiapoptotic effects of elevated Ca(2+) could be indirect and mediated via
      PTHrP. However, blocking the type 1 PTH receptor with PTH (7-34) peptide did not
      alter either high Ca(2+)-induced proliferation or protection against apoptosis.
      Taken together, our data show that activation of PI3K and p38 MAPK but not of
      MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords
      protection against apoptosis. These effects are likely direct without the
      involvement of PTHrP in an autocrine mode.

PMID- 14645112
TI  - Evidence for similar expression of protein C inhibitor and the urokinase-type
      plasminogen activator system during mouse testis development.
AB  - Plasminogen activators (PAs) and their inhibitors (PAIs) are predicted to be
      involved in the restructuring events that characterize the testis throughout
      development. We here demonstrate that PAI-3 or protein C (PC) inhibitor (PCI) was
      expressed in a sexually dimorphic fashion during mouse gonad genesis, whereas PAI
      1 and -2 exhibited no sex differences. PCI transcripts accumulated rapidly in the
      male gonad, from 12.5 d postcoitum onward. Western blot and immunohistochemistry
      analyses confirmed that male, but not female, fetal gonads produced PCI, and that
      Leydig cells are the site of PCI synthesis. The occurrence of testicular target
      proteases for PCI, i.e. PC and urokinase- and tissue-type PA, was further tracked
      using RT-PCR, plasminogen zymography, and/or immunohistochemistry. PC and tissue
      type PA showed no variation between sexes. By contrast, urokinase-type PA and its
      receptor (uPAR; which dictates the site and extent of proteolysis) exhibited sex
      differences from 13.5-14.5 d postcoitum. At that time, uPAR expression was
      restricted to Leydig cells. At earlier ages, uPAR was uniformly and widely
      distributed in the gonads of both sexes. In adult testes, PCI and uPAR
      immunoreactivities were also present in Leydig cells. In addition, PCI, PC, and
      uPAR had a germinal origin. Collectively, these results support the hypothesis
      that PCI may contribute to proteolysis equilibrium within the testis by acting in
      tandem with urokinase in Leydig cells and with PC and/or urokinase in
      spermatogenic cells. It will be important to determine how this role is linked to
      the phenotype of sterility reported elsewhere in male mice with pci deleted.

PMID- 14645113
TI  - Molecular characterization of postnatal development of testicular steroidogenesis
      in luteinizing hormone receptor knockout mice.
AB  - We recently demonstrated that the sexual development of LH receptor (LHR)
      knockout mice is normal until birth, but is totally arrested thereafter. To study
      further the functional defects of LHR knockout mice, the expression of selected
      Leydig cell-specific genes was studied in (-/-) and control (+/+) mice between
      birth and adulthood. Testis weights were similar at birth in both types of mice,
      but after about 3 wk, the (-/-) testes remained significantly lighter, weighing
      only 18% of (+/+) testes on d 70. Testicular testosterone (T) content on d 1 was
      also similar in (-/-) and (+/+) testes, but it was 97% reduced by d 70 in the
      former. Likewise, testicular T production in vitro was similar in neonatal (-/-)
      and (+/+) testes, but became undetectable in adult (-/-) testes. The mRNA
      expression of cytochrome P450 side-chain cleavage, 17 alpha-hydroxylase
      cytochrome P450, 17 beta-hydroxysteroid dehydrogenase type III, 3 beta
      hydroxysteroid dehydrogenase I (3 beta HSDI), steroidogenic acute regulatory
      protein, and relaxin-like factor were similar in newborn (-/-) and (+/+) testes,
      but became gradually very low/undetectable in (-/-) mice. The only exception was
      the persistently high expression of 3 beta HSDI in peritubular Leydig precursor
      and mesenchymal cells of the (-/-) testes at all ages. Immunohistochemistry and
      Western hybridization studies confirmed the above findings. In conclusion, LH
      action is not essential for the differentiation and function of mouse fetal
      Leydig cells, but, with the exception of 3 beta HSDI, the expression of the key
      genes of endocrine function of adult Leydig cells is dependent on LH signaling.

PMID- 14645114
TI  - Prostaglandin mediates premature delivery in pregnant sheep induced by estradiol
      at 121 days of gestational age.
AB  - The experiments reported here were designed for both in vivo and in vitro
      approaches in the same animals to obtain a better picture of the role of estrogen
      in the control of parturition. Chronically catheterized pregnant ewes were
      treated with vehicle (n = 5) or estradiol (n = 6), 5 mg twice a day, im for 2 d
      starting at d 119 of gestation. Maternal and fetal plasma estradiol,
      progesterone, and cortisol were measured by RIA and maternal plasma prostaglandin
      (PG) F2alpha was measured by enzyme immunoassay. Intrauterine PG H synthase 2
      mRNA and protein and placental P450(c17)alpha hydroxylase mRNA were determined by
      Northern, in situ hybridization, Western blot analysis, and immunocytochemistry.
      Data were analyzed by ANOVA. Five of six estradiol-treated ewes delivered their
      fetuses within 48 h; however, the placenta was still retained 5-6 h after fetal
      delivery. Both maternal plasma estradiol and PGF2 alpha increased significantly
      in the estradiol-treated group. Maternal and fetal plasma progesterone and
      cortisol were not altered in either group. There were significant increases of
      PGH synthase 2 mRNA and protein in myometrium, endometrium, and maternal placenta
      but not in fetal placenta in estradiol-treated ewes. Placental P450(c17)alpha
      hydroxylase mRNA was not detectable in vehicle or estradiol-treated groups.
      Estradiol can, in the absence of increase in plasma cortisol, stimulate uterine
      PG production and induce labor, resulting in fetal delivery in the sheep. Failure
      of placental delivery after estradiol treatment suggests that estradiol alone is
      insufficient to stimulate some of the key changes required to complete delivery
      at the stage of gestation studied.

PMID- 14645115
TI  - Neonatal mice possessing an Sry transgene show a masculinized pattern of
      progesterone receptor expression in the brain independent of sex chromosome
      status.
AB  - To assess the relative roles of sex chromosome genes and gonadal steroid hormones
      in producing sex differences in progesterone receptor (PR) expression in the
      forebrain of neonatal mice, we used mice in which the Sry gene had been deleted
      from the Y-chromosome and inserted as a transgene on an autosome in both XX and
      XY genotypes. Levels of PR immunoreactivity (PRir) in the anteroventral
      periventricular nucleus, the medial preoptic nucleus, and the ventromedial
      nucleus were significantly higher in mice that possessed an Sry transgene
      compared with mice that lacked an Sry transgene, regardless of their complement
      of sex chromosomes (XX vs. XY). This result suggests that sexual differentiation
      of PR expression in these regions is likely controlled mainly by gonadal
      hormones, not by the genetic sex of the brain cells. No differences in PRir were
      detected between wild-type XY mice with the Sry gene on the Y-chromosome and XY
      mice with the Sry transgene, suggesting that testicular hormones produced in
      these two genotypes have comparable effects on neural tissue.

PMID- 14645116
TI  - Dehydroepiandrosterone increases hippocampal spine synapse density in
      ovariectomized female rats.
AB  - This study tests the hypothesis that dehydroepiandrosterone (DHEA) stimulates
      formation of hippocampal CA1 spine synapses in ovariectomized rats. Subcutaneous
      injections of DHEA (1 mg/d for 2 d) increased CA1 spine synapse density by more
      than 50% compared with vehicle-injected animals. The effect of DHEA on CA1
      synapse density was abolished by pretreatment with the nonsteroidal aromatase
      inhibitor, letrozole. DHEA treatment, with or without letrozole, had no
      detectable uterotrophic effect. These observations are consistent with the
      hypothesis that DHEA treatment may be capable of reversing the decline in
      hippocampal spine synapse density observed after loss of ovarian steroid hormone
      secretion. The blockade of the synaptic response to DHEA by letrozole, despite
      the lack of a uterotrophic response to this steroid, suggests that the
      hippocampal response to DHEA may be mediated via aromatization in the brain.

PMID- 14645117
TI  - In situ analysis of interleukin-1-induced transcription of cox-2 and il-8 in
      cultured human myometrial cells.
AB  - The specific binding of transcription factors to DNA has been shown to be
      inhibited by chromatin structure and increased by cooperative interactions with
      other proteins. Consequently, in situ analysis using chromatin
      immunoprecipitation offers the most accurate view of transcriptional control.
      Transient transfection studies and in vitro analyses of IL-1-induced cox-2
      transcription in a number of cell types have indicated regulation by either
      nuclear factor kappa B (NF-kappa B) or CCAAT/enhancer binding protein (C/EBP
      beta), or both acting cooperatively. To determine the mechanisms of COX-2
      (cyclooxygenase or prostaglandin endoperoxide synthase) induction in cultured
      human myometrial cells in situ, we examined the cross-linking of the RelA subunit
      of NF-kappa B and C/EBP beta to the cox-2 promoter and flanking sequences. As a
      control, we inspected the interaction of these transcription factors with the IL
      8 gene, which has been shown in other cell types to be activated by the
      cooperative interaction of NF-kappa B and C/EBP beta. Indeed, both transcription
      factors were cross-linked to the il-8 promoter after IL-1 treatment, but only
      RelA was cross-linked to cox-2 DNA. The il-8 promoter was also found to
      physically interact with proteins cross-linked to sites further upstream. IL-1
      treatment also increased polymerase II cross-linking to both promoters and
      increased histone H4 acetylation at specific sites. These results indicate that
      modification of chromatin structure is part of the response to IL-1 stimulation.
      Chromatin immunoprecipitation thus provides critical insight into the mechanisms
      of COX-2 and IL-8 expression in human myometrial cells.

PMID- 14645118
TI  - Gamma-aminobutyric acid neurons integrate and rapidly transmit permissive and
      inhibitory metabolic cues to gonadotropin-releasing hormone neurons.
AB  - Negative energy balance inhibits fertility by decreasing GnRH release; however,
      the mechanisms are not well understood. GnRH neurons can be excited by activation
      of gamma-aminobutyric acid (GABA)(A) receptors, and GABAergic neurons provide a
      major synaptic input. We hypothesized that permissive metabolic signals mediated
      by leptin and inhibitory signals conveyed by neuropeptide Y (NPY) and opiates
      rapidly alter GABA(A) receptor-mediated drive to GnRH neurons. In fed and fasted
      female mice, GABAergic postsynaptic currents (PSCs) were recorded from GnRH
      neurons before and after in vitro treatment with leptin, NPY, or met-enkephalin.
      Leptin increased PSC frequency in fed and fasted mice, indicating that it
      increased presynaptic activity. Leptin also increased PSC size. Inhibiting leptin
      receptor signaling pathways within GnRH neurons abolished the latter effect,
      indicating a direct action on these cells. In fed, but not fasted, mice, NPY and
      met-enkephalin decreased PSC frequency in an antagonist-reversible manner, but
      did not alter PSC size. NPY-1 receptor antagonists alone increased frequency in
      fed and fasted mice, as did opiate receptor blockade in fasted animals,
      suggesting that endogenous NPY and opiates modulate GABAergic drive to GnRH
      neurons. These data suggest that GABAergic afferents integrate metabolic signals
      for delivery to GnRH neurons. Decreased sensitivity to NPY and opiates in fasted
      mice indicate that these peptides send physiologically relevant signals regarding
      energy balance to GnRH neurons.

PMID- 14645119
TI  - Photoperiodic regulation of leptin sensitivity in the Siberian hamster, Phodopus
      sungorus, is reflected in arcuate nucleus SOCS-3 (suppressor of cytokine
      signaling) gene expression.
AB  - We present the first evidence that suppressor of cytokine signaling-3 (SOCS3), a
      protein inhibiting Janus kinase/signal transducer and activator of transcription
      (STAT) signaling distal of the leptin receptor, conveys seasonal changes in
      leptin sensitivity in the Siberian hamster. Food deprivation (48 h) reduced SOCS3
      gene expression in hamsters acclimated to either long (LD) or short (SD)
      photoperiods, suggesting that leptin signals acute starvation regardless of
      photoperiod. However, SOCS3 mRNA levels were substantially lower in the
      hypothalamic arcuate nucleus of hamsters acclimated to SD than in those raised in
      LD. In juveniles raised in LD, a rapid increase in SOCS3 mRNA was observed within
      4 d of weaning, which was completely prevented by transfer to SD on the day of
      weaning. The early increase in SOCS3 gene expression in juvenile hamsters in LD
      clearly preceded the establishment of different body weight trajectories in LD
      and SD. In adult LD hamsters, SOCS3 mRNA was maintained at an elevated level
      despite the chronic food restriction imposed to lower body weight and serum
      leptin to or even below SD levels. A single injection of leptin in SD hamsters
      elevated SOCS3 mRNA to LD levels, whereas leptin treatment had no effect on SOCS3
      gene expression in LD hamsters. Our results suggest that the development of
      leptin resistance in LD-acclimated hamsters involves SOCS3-mediated suppression
      of leptin signaling in the arcuate nucleus. Increased SOCS3 expression in LD
      hamsters is independent of body fat and serum leptin levels, suggesting that the
      photoperiod is able to trigger the biannual reversible switch in leptin
      sensitivity.

PMID- 14645120
TI  - Cilostazol, an inhibitor of type 3 phosphodiesterase, stimulates large
      conductance, calcium-activated potassium channels in pituitary GH3 cells and
      pheochromocytoma PC12 cells.
AB  - The effects of cilostazol, a dual inhibitor of type 3 phosphodiesterase and
      adenosine uptake, on ion currents were investigated in pituitary GH(3) cells and
      pheochromocytoma PC12 cells. In whole-cell configuration, cilostazol (10 microm)
      reversibly increased the amplitude of Ca(2+)-activated K(+) current [I(K(Ca))].
      Cilostazol-induced increase in I(K(Ca)) was suppressed by paxilline (1 microM)
      but not glibenclamide (10 microm), dequalinium dichloride (10 microM), or beta
      bungarotoxin (200 nM). Pretreatment of adenosine deaminase (1 U/ml) or alpha,beta
      methylene-ADP (100 microM) for 5 h did not alter the magnitude of cilostazol
      stimulated I(K(Ca)). Cilostazol (30 microM) slightly suppressed voltage-dependent
      l-type Ca(2+) current. In inside-out configuration, bath application of
      cilostazol (10 microM) into intracellular surface caused no change in single
      channel conductance; however, it did increase the activity of large-conductance
      Ca(2+)-activated K(+) (BK(Ca)) channels. Cilostazol enhanced the channel activity
      in a concentration-dependent manner with an EC(50) value of 3.5 microM.
      Cilostazol (10 microM) shifted the activation curve of BK(Ca) channels to less
      positive membrane potentials. Changes in the kinetic behavior of BK(Ca) channels
      caused by cilostazol were related to an increase in mean open time and a decrease
      in mean closed time. Under current-clamp configuration, cilostazol decreased the
      firing frequency of action potentials. In pheochromocytoma PC12 cells, cilostazol
      (10 microM) also increased BK(Ca) channel activity. Cilostazol-mediated
      stimulation of I(K(Ca)) appeared to be not linked to its inhibition of adenosine
      uptake or phosphodiesterase. The channel-stimulating properties of cilostazol
      may, at least in part, contribute to the underlying mechanisms by which it
      affects neuroendocrine function.

PMID- 14645121
TI  - Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily
      conserved genetic mechanisms for vertebrate head specification.
AB  - The Otx2 gene, containing a highly conserved paired-type homeobox, plays a
      pivotal role in the development of the rostral head throughout vertebrates.
      Precise regulation of the temporal and spatial expression of Otx2 is likely to be
      crucial for proper head specification. However, regulatory mechanisms of Otx2
      expression remain largely unknown. In this study, the Otx2 genome of the puffer
      fish Fugu rubripes, which has been proposed as a model vertebrate owing to its
      highly compact genome, was cloned. Consistently, Fugu Otx2 possesses introns
      threefold smaller in size than those of the mouse Otx2 gene. Otx2 mRNA was
      transcribed after MBT, and expressed in the rostral head region throughout the
      segmentation and pharyngula periods of wild-type Fugu embryos. To elucidate
      regulatory mechanisms of Otx2 expression, the expression of Otx2-lacZ reporter
      genes nearly covering the Fugu Otx2 locus, from -30.5 to +38.5 kb, was analyzed,
      by generating transgenic mice. Subsequently, seven independent cis-regulators
      were identified over an expanse of 60 kb; these regulators are involved in the
      mediation of spatiotemporally distinct subdomains of Otx2 expression.
      Additionally, these expression domains appear to coincide with local signaling
      centers and developing sense organs. Interestingly, most domains do not overlap
      with one another, which implies that cis-regulators for redundant expression may
      be abolished exclusively in the pufferfish so as to reduce its genome size.
      Moreover, these cis-regions were also able to direct expression in zebrafish
      embryos equivalent to that observed in transgenic mice. Further comparative
      sequence analysis of mouse and pufferfish intergenic regions revealed eight
      highly conserved elements within these cis-regulators. Therefore, we propose
      that, in vertebrate evolution, the Otx2 promoter acquires multiple,
      spatiotemporally specific cis-regulators in order to precisely control highly
      coordinated processes in head development.

PMID- 14645122
TI  - Integration of complex larval chemosensory organs into the adult nervous system
      of Drosophila.
AB  - The sense organs of adult Drosophila, and holometabolous insects in general,
      derive essentially from imaginal discs and hence are adult specific. Experimental
      evidence presented here, however, suggests a different developmental design for
      the three largely gustatory sense organs located along the pharynx. In a
      comprehensive cellular analysis, we show that the posteriormost of the three
      organs derives directly from a similar larval organ and that the two other organs
      arise by splitting of a second larval organ. Interestingly, these two larval
      organs persist despite extensive reorganization of the pharynx. Thus, most of the
      neurons of the three adult organs are surviving larval neurons. However, the
      anterior organ includes some sensilla that are generated during pupal stages.
      Also, we observe apoptosis in a third larval pharyngeal organ. Hence, our
      experimental data show for the first time the integration of complex, fully
      differentiated larval sense organs into the nervous system of the adult fly and
      demonstrate the embryonic origin of their neurons. Moreover, they identify
      metamorphosis of this sensory system as a complex process involving neuronal
      persistence, generation of additional neurons and neuronal death. Our conclusions
      are based on combined analysis of reporter expression from P[GAL4] driver lines,
      horseradish peroxidase injections into blastoderm stage embryos, cell labeling
      via heat-shock-induced flip-out in the embryo, bromodeoxyuridine birth dating and
      staining for programmed cell death. They challenge the general view that sense
      organs are replaced during metamorphosis.

PMID- 14645123
TI  - Developmental origin of wiring specificity in the olfactory system of Drosophila.
AB  - In both insects and mammals, olfactory receptor neurons (ORNs) expressing
      specific olfactory receptors converge their axons onto specific glomeruli,
      creating a spatial map in the brain. We have previously shown that second order
      projection neurons (PNs) in Drosophila are prespecified by lineage and birth
      order to send their dendrites to one of approximately 50 glomeruli in the
      antennal lobe. How can a given class of ORN axons match up with a given class of
      PN dendrites? Here, we examine the cellular and developmental events that lead to
      this wiring specificity. We find that, before ORN axon arrival, PN dendrites have
      already created a prototypic map that resembles the adult glomerular map, by
      virtue of their selective dendritic localization. Positional cues that create
      this prototypic dendritic map do not appear to be either from the residual larval
      olfactory system or from glial processes within the antennal lobe. We propose
      instead that this prototypic map might originate from both patterning information
      external to the developing antennal lobe and interactions among PN dendrites.

PMID- 14645124
TI  - Investigation into a role for the primitive streak in development of the murine
      allantois.
AB  - Despite its importance as the source of one of three major vascular systems in
      the mammalian conceptus, little is known about the murine allantois, which will
      become the umbilical cord of the chorio-allantoic placenta. During gastrulation,
      the allantois grows into the exocoelomic cavity as a mesodermal extension of the
      posterior primitive streak. On the basis of morphology, gene expression and/or
      function, three cell types have been identified in the allantois: an outer layer
      of mesothelial cells, whose distal portion will become transformed into chorio
      adhesive cells, and endothelial cells within the core. Formation of endothelium
      and chorio-adhesive cells begins in the distal region of the allantois, farthest
      from the streak. Over time, endothelium spreads to the proximal allantoic region,
      whilst the distal outer layer of presumptive mesothelium gradually acquires
      vascular cell adhesion molecule (VCAM1) and mediates chorio-allantoic union.
      Intriguingly, the VCAM1 domain does not extend into the proximal allantoic
      region. How these three allantoic cell types are established is not known,
      although contact with the chorion has been discounted. In this study, we have
      investigated how the allantois differentiates, with the goal of discriminating
      between extrinsic mechanisms involving the primitive streak and an intrinsic role
      for the allantois itself. Exploiting previous observations that the streak
      contributes mesoderm to the allantois throughout the latter's early development,
      microsurgery was used to remove allantoises at ten developmental stages.
      Subsequent whole embryo culture of operated conceptuses resulted in the formation
      of regenerated allantoises at all time points. Aside from being generally shorter
      than normal, none of the regenerates exhibited abnormal differentiation or
      inappropriate cell relationships. Rather, all of them resembled intact
      allantoises by morphological, molecular and functional criteria. Moreover, fate
      mapping adjacent yolk sac and amniotic mesoderm revealed that these tissues and
      their associated bone morphogenetic protein 4 (BMP4) did not contribute to
      restoration of allantoic outgrowth and differentiation during allantoic
      regeneration. Thus, on the basis of these observations, we conclude that
      specification of allantoic endothelium, mesothelium and chorio-adhesive cells
      does not occur by a streak-related mechanism during the time that proximal
      epiblast travels through it and is transformed into allantoic mesoderm. Rather,
      all three cell-types are established by mechanisms intrinsic to the allantois,
      and possibly include roles for cell age and cell position. However, although
      chorio-adhesive cells were not specified within the streak, we discovered that
      the streak nonetheless plays a role in establishing VCAM1's expression domain,
      which typically began and was thereafter maintained at a defined distance from
      the primitive streak. When allantoises were removed from contact with the streak,
      normally VCAM1-negative proximal allantoic regions acquired VCAM1. These results
      suggested that the streak suppresses formation of chorio-adhesive cells in
      allantoic mesoderm closest to it. Together with previous results, findings
      presented here suggest a model of differentiation of allantoic mesoderm that
      invokes intrinsic and extrinsic mechanisms, all of which appear to be activated
      once the allantoic bud has formed.

PMID- 14645125
TI  - Death is the major fate of medial edge epithelial cells and the cause of basal
      lamina degradation during palatogenesis.
AB  - During mammalian development, a pair of shelves fuses to form the secondary
      palate, a process that requires the adhesion of the medial edge epithelial tissue
      (MEE) of each shelf and the degeneration of the resulting medial epithelial seam
      (MES). It has been reported that epithelial-mesenchymal transformation (EMT)
      occurs during shelf fusion and is considered a fundamental process for MES
      degeneration. We recently found that cell death is a necessary process for shelf
      fusion. These findings uncovered the relevance of cell death in MES degeneration;
      however, they do not discard the participation of other processes. In the present
      work, we focus on the evaluation of the processes that could contribute to palate
      shelf fusion. We tested EMT by traditional labeling of MEE cells with a dye, by
      infection of MEE with an adenovirus carrying the lacZ gene, and by fusing wild
      type shelves with the ones from EGFP-expressing mouse embryos. Fate of MEE
      labeled cells was followed by culturing whole palates, or by a novel slice
      culture system that allows individual cells to be followed during the fusion
      process. Very few labeled cells were found in the mesenchyme compartment, and
      almost all were undergoing cell death. Inhibition of metalloproteinases prevented
      basal lamina degradation without affecting MES degeneration and MEE cell death.
      Remarkably, independently of shelf fusion, activation of cell death promoted the
      degradation of the basal lamina underlying the MEE ('cataptosis'). Finally, by
      specific labeling of periderm cells (i.e. the superficial cells that cover the
      basal epithelium), we observed that epithelial triangles at oral and nasal ends
      of the epithelial seam do not appear to result from MEE cell migration but rather
      from periderm cell migration. Inhibition of migration or removal of these
      periderm cells suggests that they have a transient function controlling MEE cell
      adhesion and survival, and ultimately die within the epithelial triangles. We
      conclude that MES degeneration occurs almost uniquely by cell death, and for the
      first time we show that this process can activate basal lamina degradation during
      a developmental process.

PMID- 14645126
TI  - Atrophin 2 recruits histone deacetylase and is required for the function of
      multiple signaling centers during mouse embryogenesis.
AB  - Atrophins are evolutionarily conserved proteins that are thought to act as
      transcriptional co-repressors. Mammalian genomes contain two atrophin genes.
      Dominant polyglutamine-expanded alleles of atrophin 1 have been identified as the
      cause of dentatorubralpallidoluysian atrophy, an adult-onset human
      neurodegenerative disease with similarity to Huntington's. In a screen for
      recessive mutations that disrupt patterning of the early mouse embryo, we
      identified a line named openmind carrying a mutation in atrophin 2. openmind
      homozygous embryos exhibit a variety of patterning defects that first appear at
      E8.0. Defects include a specific failure in ventralization of the anterior neural
      plate, loss of heart looping and irregular partitioning of somites. In mutant
      embryos, Shh expression fails to initiate along the anterior midline at E8.0, and
      Fgf8 is delocalized from the anterior neural ridge at E8.5, revealing a crucial
      role for atrophin 2 in the formation and function of these two signaling centers.
      Atrophin 2 is also required for normal organization of the apical ectodermal
      ridge, a signaling center that directs limb pattern. Elevated expression of
      atrophin 2 in neurons suggests it may interact with atrophin 1 in neuronal
      development or function. We further show that atrophin 2 associates with histone
      deacetylase 1 in mouse embryos, providing a biochemical link between Atr2 and a
      chromatin-modifying enzyme. Based on our results, and on those of others, we
      propose that atrophin proteins act as transcriptional co-repressors during
      embryonic development.

PMID- 14645127
TI  - Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan
      sulfate proteoglycans.
AB  - The signaling molecules Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg)
      function as morphogens and organize wing patterning in Drosophila. In the screen
      for mutations that alter the morphogen activity, we identified novel mutants of
      two Drosophila genes, sister of tout-velu (sotv) and brother of tout-velu (botv),
      and new alleles of tout-velu (ttv). The encoded proteins of these genes belong to
      an EXT family of proteins that have or are closely related to glycosyltransferase
      activities required for biosynthesis of heparan sulfate proteoglycans (HSPGs).
      Mutation in any of these genes impaired biosynthesis of HSPGs in vivo, indicating
      that, despite their structural similarity, they are not redundant in the HSPG
      biosynthesis. Protein levels and signaling activities of Hh, Dpp and Wg were
      reduced in the cells mutant for any of these EXT genes to a various degree, Wg
      signaling being the least sensitive. Moreover, all three morphogens were
      accumulated in the front of EXT mutant cells, suggesting that these morphogens
      require HSPGs to move efficiently. In contrast to previous reports that ttv is
      involved exclusively in Hh signaling, we found that ttv mutations also affected
      Dpp and Wg. These data led us to conclude that each of three EXT genes studied
      contribute to Hh, Dpp and Wg morphogen signaling. We propose that HSPGs
      facilitate the spreading of morphogens and therefore, function to generate
      morphogen concentration gradients.

PMID- 14645128
TI  - A distinct patterning mechanism of O and P cell fates in the development of the
      rostral segments of the leech Helobdella robusta: implications for the
      evolutionary dissociation of developmental pathway and morphological outcome.
AB  - Despite a high degree of homonomy in the segmental organization of the ectoderm,
      the body plan of the leech is divided into two zones based on the distinct cell
      lineage patterns that give rise to the O/P portion of the segmental ectoderm. In
      the midbody and caudal segments, each segmental repeat of ectoderm arises in part
      from one 'o' blast cell and one 'p' blast cell. These two blast cells are
      positionally specified to distinct O and P fates, and give rise to differentiated
      descendant cells called O and P pattern elements, respectively. In the rostral
      segments, each segmental repeat of O and P pattern elements arises from a single
      'op' blast cell. Based on their developmental fates and their responses to the
      ablation of neighboring cells, the granddaughters of the primary op blast cell
      are categorized into two O-type cells and two P-type cells. The O-type cells do
      not require the presence of the rest of the op blast cell clone for their normal
      development. By contrast, normal development of the P-type cells depends upon
      interactions with the other OP sublineages. Additional experiments showed that
      the O-type cells are the source of a repressive signal involved in the normal
      fate specification of the P-type cells. Our data suggest that the cell
      interactions involved in fate specification differ substantially in the rostral
      and midbody segments, even though the set of differentiated descendants produced
      by the rostral OP pathway and the midbody O and P pathways are very similar.

PMID- 14645129
TI  - rigor mortis encodes a novel nuclear receptor interacting protein required for
      ecdysone signaling during Drosophila larval development.
AB  - Pulses of the steroid hormone ecdysone trigger the major developmental
      transitions in Drosophila, including molting and puparium formation. The ecdysone
      signal is transduced by the EcR/USP nuclear receptor heterodimer that binds to
      specific response elements in the genome and directly regulates target gene
      transcription. We describe a novel nuclear receptor interacting protein encoded
      by rigor mortis (rig) that is required for ecdysone responses during larval
      development. rig mutants display defects in molting, delayed larval development,
      larval lethality, duplicated mouth parts, and defects in puparium formation-
      phenotypes that resemble those seen in EcR, usp, E75A and betaFTZ-F1 mutants.
      Although the expression of these nuclear receptor genes is essentially normal in
      rig mutant larvae, the ecdysone-triggered switch in E74 isoform expression is
      defective. rig encodes a protein with multiple WD-40 repeats and an LXXLL motif,
      sequences that act as specific protein-protein interaction domains. Consistent
      with the presence of these elements and the lethal phenotypes of rig mutants, Rig
      protein interacts with several Drosophila nuclear receptors in GST pull-down
      experiments, including EcR, USP, DHR3, SVP and betaFTZ-F1. The ligand binding
      domain of betaFTZ-F1 is sufficient for this interaction, which can occur in an AF
      2-independent manner. Antibody stains reveal that Rig protein is present in the
      brain and imaginal discs of second and third instar larvae, where it is
      restricted to the cytoplasm. In larval salivary gland and midgut cells, however,
      Rig shuttles between the cytoplasm and nucleus in a spatially and temporally
      regulated manner, at times that correlate with the major lethal phase of rig
      mutants and major switches in ecdysone-regulated gene expression. Taken together,
      these data indicate that rig exerts essential functions during larval development
      through gene-specific effects on ecdysone-regulated transcription, most likely as
      a cofactor for one or more nuclear receptors. Furthermore, the dynamic
      intracellular redistribution of Rig protein suggests that it may act to refine
      spatial and temporal responses to ecdysone during development.

PMID- 14645130
TI  - Cellular mechanism of vasoconstriction induced by angiotensin II: it remains to
      be determined.

PMID- 14645131
TI  - Atrioventricular nodal electrophysiology: still exciting after all these years.

PMID- 14645132
TI  - Blocking stretch-induced myocardial remodeling.

PMID- 14645133
TI  - Thioredoxin: a key regulator of cardiovascular homeostasis.
AB  - The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous
      thiol oxidoreductase system that regulates cellular reduction/oxidation (redox)
      status. The oxidation mechanism for disease pathogenesis states that an imbalance
      in cell redox state alters function of multiple cell pathways. In this study, we
      review the essential role for TRX to limit oxidative stress directly via
      antioxidant effects and indirectly by protein-protein interaction with key
      signaling molecules, such as apoptosis signal-regulating kinase 1. We propose
      that TRX and its endogenous regulators are important future targets to develop
      clinical therapies for cardiovascular disorders associated with oxidative stress.

PMID- 14645134
TI  - Regulation of gene expression by cyclic GMP.
AB  - Cyclic GMP, produced in response to nitric oxide and natriuretic peptides, is a
      key regulator of vascular smooth muscle cell contractility, growth, and
      differentiation, and is implicated in opposing the pathophysiology of
      hypertension, cardiac hypertrophy, atherosclerosis, and vascular
      injury/restenosis. cGMP regulates gene expression both positively and negatively
      at transcriptional as well as at posttranscriptional levels. cGMP-regulated
      transcription factors include the cAMP-response element binding protein CREB, the
      serum response factor SRF, and the nuclear factor of activated T cells NF/AT.
      cGMP can regulate CREB directly, through phosphorylation by cGMP-dependent
      protein kinase, or indirectly, through activation of mitogen-activated protein
      kinase pathways; regulation of SRF and NF/AT by cGMP is indirect, through
      modulation of RhoA and calcineurin signaling, respectively. Downregulation of the
      RNA-binding protein HuR by cGMP leads to destabilization of guanylate cyclase
      mRNA, but this posttranscriptional mechanism may affect many more cGMP-regulated
      genes. In this review, we discuss the role of cGMP-regulated gene expression in
      (patho)physiological processes most relevant to the cardiovascular system, such
      as regulation of vascular tone, cardiac hypertrophy, phenotypic modulation of
      vascular smooth muscle cells, and regulation of cell proliferation and apoptosis.

PMID- 14645135
TI  - Proteomic approaches to analyze the dynamic relationships between
      nucleocytoplasmic protein glycosylation and phosphorylation.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) is both an abundant and dynamic
      posttranslational modification similar to phosphorylation that occurs on serine
      and threonine residues of cytosolic and nuclear proteins in all metazoans and
      cell types examined, including cardiovascular tissue. Since the discovery of O
      GlcNAc more than 20 years ago, the elucidation of O-GlcNAc as a posttranslational
      modification has been slow, albeit similar to the rate of acceptance of
      phosphorylation, because of the lack of tools available for its study.
      Identifying O-GlcNAc posttranslational modifications on proteins is a major
      challenge to proteomics. The recent development of mild beta-elimination followed
      by Michael addition with dithiothreitol has significantly improved the site
      mapping of both O-GlcNAc and O-phosphate in functional proteomics. beta
      Elimination followed by Michael addition with dithiothreitol facilitates the
      study of the labile O-GlcNAc modification in the etiology of disease states. We
      discuss how recent technological innovations will expand our present
      understanding of O-GlcNAc and what the implications are for diabetes and
      cardiovascular complications.

PMID- 14645136
TI  - Alternative splicing of cGMP-dependent protein kinase I and nitrate tolerance.

PMID- 14645137
TI  - Urantide: an ultrapotent urotensin II antagonist peptide in the rat aorta.
AB  - In this study we describe the ability of two human urotensin-II (hU-II)
      derivatives [Pen5,Orn8]hU-II(4-11) and [Pen5,DTrp7,Orn8]hU-II(4-11) (urantide) to
      block hU-II-induced contractions in the rat isolated thoracic aorta. Both
      compounds competitively antagonized hU-II- induced effects with pKB=7.4+/-0.06
      (n=12) and pKB=8.3+/-0.09 (n=12), respectively. In contrast, neither
      [Pen5,Orn8]hU-II(4-11) nor urantide (1 microm each) was able to modify
      noradrenaline- or endothelin 1-induced contractile effects. At micromolar
      concentrations, [Pen5,Orn8]hU-II(4-11) produced weak (< or =25% of hU-II maximum)
      agonist responses in the rat aorta, whereas urantide was totally uneffective as
      agonist up to 1 microm. In addition, [Pen5,Orn8]hU-II(4-11) and urantide
      displaced [125I]urotensin II from specific binding at hU-II recombinant receptors
      (UT receptors) transfected into CHO/K1 cells (pKi=7.7+/-0.05, n=4 and pKi=8.3+/
      0.04, n=4, respectively). To our knowledge, urantide is the most potent UT
      receptor antagonist so far described, and might represent a useful tool for
      exploring the (patho)physiological role of hU-II in the mammalian cardiovascular
      system.

PMID- 14645138
TI  - Acute exposure of ceramide enhances cardiac contractile function in isolated
      ventricular myocytes.
AB  - 1. The sphingolipid ceramide, a primary building block for all other
      sphingolipids, is associated with growth arrest, apoptosis, and lipotoxic
      dysfunction. Interestingly, ceramide may attenuate high glucose-induced myocyte
      dysfunction, produce Ca2+ influx, and augment smooth muscle contraction. To
      determine the role of ceramide on cardiac excitation-contraction (E-C) coupling,
      electrically paced adult rat ventricular myocytes were acutely exposed to a cell
      permeable ceramide analog (10 pm-100 microM) and the following indices were
      determined: peak shortening (PS), time-to-PS, time-to-90% relengthening, and the
      maximal velocity of shortening and relengthening (+/-dLdt). Intracellular Ca2+
      properties were assessed using fura-2AM fluorescent microscopy. 2. Our results
      revealed a concentration- and time-dependent increase of PS in ventricular
      myocytes in response to ceramide associated with an increase in +/-dLdt. The
      maximal increase in PS was approximately 35% from control value and was
      maintained throughout the first 20 min of ceramide exposure. However, the
      ceramide-induced increase in PS was not maintained once the exposure time was
      beyond 20 min. Acute exposure of ceramide significantly enhanced intracellular
      Ca2+ release, although at a much lower concentration range. The ceramide-induced
      augmentation of PS was not significantly affected by inhibition of
      phosphatidylinositol (PI)-3-kinase, protein kinase C (PKC), ceramide-activated
      protein phosphatase (CAPP), and nitric oxide (NO) synthase. 3. Our data suggest
      that ceramide acutely augments the contractile function of cardiac myocytes
      through an alternative mechanism(s) rather than PI-3-kinase, PKC, CAPP, or NO.

PMID- 14645139
TI  - Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T
      cells.
AB  - 1. Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent
      decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N
      dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced
      acidification as a function of time, indicating that the exchanger is implicated
      in pHi recovery. 2. Other fatty acids like oleic acid, arachidonic acid,
      eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these
      cells. 3. To assess the role of calcium in the DHA-induced acidification, we
      conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+)
      buffer. We observed that there was no difference in the degree of DHA-induced
      transient acidification in both the experimental conditions, though pHi recovery
      was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. 4. In the presence of
      BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed.
      Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi
      recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in
      [Ca2+]i, though this fatty acid still induced a rapid acidification in these
      cells. These observations suggest that calcium is implicated in the long-lasting
      DHA-induced acidosis. 5. DHA-induced rapid acidification may be due to its
      deprotonation in the plasma membrane (flip-flop model), as suggested by the
      following observations: (1) DHA with a -COOH group induced intracellular
      acidification, but this fatty acid with a -COOCH3 group failed to do so, and (2)
      DHA, but not propionic acid, -induced acidification was completely reversed by
      addition of fatty acid-free bovine serum albumin in these cells. 6. These results
      suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in
      human T-cells.

PMID- 14645140
TI  - Ouabain exerts biphasic effects on connexin functionality and expression in
      vascular smooth muscle cells.
AB  - 1. We have compared the effects of ouabain on the maintenance of gap junctional
      communication in rat aortic A7r5 smooth muscle cells, monkey COS-1 fibroblasts
      and human HeLa epithelial cells. 2. Ouabain (1 mM) interrupted dye coupling
      between confluent A7r5 cells within approximately 1 h, and high concentrations of
      ouabain were similarly required to reduce coupling between COS-1 cells selected
      to express the rat alpha1 Na+/K+-ATPase subunit, which is ouabain resistant. By
      contrast, low concentrations of ouabain (1-10 microM) attenuated dye transfer in
      wild-type COS-1 and HeLa cells, whose endogenous alpha1 subunits possess
      relatively high affinity for the glycoside (Ki approximately 0.3 vs approximately
      100 microM) Ouabain-induced reductions in dye transfer therefore correlated with
      the ability of the glycoside to bind to the Na+/K+-ATPase isoenzymes expressed in
      these different cell lines. 3. No consistent relationship between inhibition of
      intercellular dye transfer and secondary changes in [Ca2+]i or pHi could be
      identified following incubation with ouabain. 4. In separate experiments, the
      effects of ouabain on real-time trafficking of connexin protein were monitored by
      time-lapse microscopy of A7r5 cells transfected to express a fluorescent Cx43
      green fluorescent protein (GFP) and the ability of the glycoside to modulate
      endogenous expression of connexins (Cx) 40 and 43 evaluated in A7r5 cells by
      immunochemical and Western blot analysis. 5. Ouabain (1 mM) depressed vesicular
      trafficking of Cx43-GFP after approximately 1 h, and caused a time-dependent loss
      of endogenous Cx40 and Cx43 protein that was first evident at 2 h and almost
      complete after 4 h. These effects of ouabain on Cx expression were reversed
      approximately 90 min following washout of the glycoside. 6. We conclude that
      ouabain exerts biphasic effects on the intercellular communication that involve
      an initial decrease in gap junctional permeability followed by a global reduction
      in the expression of Cx protein. Further studies are necessary to establish to
      what extent these actions of ouabain reflect inversion of the normal [Na+]i/[K+]i
      ratio and/or conversion of the Na+/K+-ATPase into a general signal transducer
      that regulates downstream protein synthesis.

PMID- 14645141
TI  - Inhibition of human alpha 7 nicotinic acetylcholine receptors by open channel
      blockers of N-methyl-D-aspartate receptors.
AB  - 1. Human alpha 7 nicotinic acetylcholine (ACh) receptors were expressed in
      Xenopus oocytes and the effects of the N-methyl-D-aspartate (NMDA) receptor open
      channel blockers memantine and cerestat on this receptor were examined using two
      electrode voltage-clamp recordings and 125I-alpha-bungarotoxin (125I-alpha-bgtx)
      binding. 2. Memantine and cerestat produced complete inhibition of ACh-induced
      inward currents with affinities similar to that reported for native NMDA
      receptors. Cerestat, IC50 1.7 (-1; +2) microm, was more potent than memantine,
      IC50 5 (-3;+8) microM, and the effects of both drugs were fully and rapidly
      reversible. 3. Inhibition of alpha 7 receptor function was voltage-independent,
      and it occurred at concentrations far lower than those needed to inhibit (never
      completely) binding of 125I-alpha-bgtx to alpha 7 receptors, suggesting that the
      effects of memantine or cerestat are noncompetitive. 4. These results provide
      evidence that human alpha 7 receptors are inhibited by memantine and cerestat and
      suggest that caution should be applied when using these compounds to study
      systems in which NMDA and nACh receptors co-exist.

PMID- 14645142
TI  - N-salicyloyltryptamine, a new anticonvulsant drug, acts on voltage-dependent Na+,
      Ca2+, and K+ ion channels.
AB  - 1. The aim of this work was to study the effects of N-salicyloyltryptamine (STP),
      a novel anticonvulsant agent, on voltage-gated ion channels in GH3 cells. 2. In
      this study, we show that STP at 17 microM inhibited up to 59.2+/-10.4% of the Ito
      and 73.1+/-8.56% of the IKD K+ currents in GH3 cells. Moreover, the inhibitory
      activity of the drug STP on K+ currents was dose-dependent (IC50=34.6+/-8.14
      microM for Ito) and partially reversible after washing off. 3. Repeated
      stimulation at 1 Hz (STP at 17 microM) led to the total disappearance of Ito
      current, and an enhancement of IKD. 4. In the cell-attached configuration,
      application of STP to the bath increased the open probability of large
      conductance Ca2+-activated K+ channels. 5. STP at 17 microM inhibited the L-type
      Ca2+ current by 54.9+/-7.50% without any significant changes in the voltage
      dependence. 6. STP at 170 microM inhibited the TTX-sensitive Na+ current by
      22.1+/-2.41%. At a lower concentration (17 microM), no effect on INa was
      observed. 7. The pharmacological profile described here might contribute to the
      neuroprotective effect exerted by this compound in experimental 'in vivo' models.

PMID- 14645144
TI  - Critical periods of brain growth and cognitive function in children.
AB  - There is evidence that IQ tends to be higher in those who were heavier at birth
      or who grew taller in childhood and adolescence. Although these findings imply
      that growth in both foetal and postnatal life influences cognitive performance,
      little is known about the relative importance of brain growth during different
      periods of development. We investigated the relationship between brain growth in
      different periods of pre- and postnatal life and cognitive function in 221 9-year
      old children whose mothers had taken part in a study of nutrition in pregnancy
      and whose head circumference had been measured at 18 weeks gestation, birth and 9
      months of age. Cognitive function of the children and their mothers was assessed
      with the Wechsler Abbreviated Scale of Intelligence. Full-scale IQ at age 9 years
      rose by 1.98 points [95% confidence interval (CI) 0.34 to 3.62] for each SD
      increase in head circumference at 9 months and by 2.87 points (95% CI 1.05 to
      4.69) for each SD increase in head circumference at 9 years of age, after
      adjustment for sex, number of older siblings, maternal IQ, age, education, social
      class, duration of breastfeeding and history of low mood in the post-partum
      period. Postnatal head growth was significantly greater in children whose mothers
      were educated to degree level or of higher socio-economic status. There was no
      relation between IQ and measurements of head size at 18 weeks gestation or at
      birth. These results suggest that brain growth during infancy and early childhood
      is more important than growth during foetal life in determining cognitive
      function.

PMID- 14645143
TI  - Anandamide initiates Ca(2+) signaling via CB2 receptor linked to phospholipase C
      in calf pulmonary endothelial cells.
AB  - The endocannabinoid anandamide has been reported to affect neuronal cells, immune
      cells and smooth muscle cells via either CB1 or CB2 receptors. In endothelial
      cells, the receptors involved in activating signal transduction are still
      unclear, despite the fact that anandamide is produced in this cell type. The
      present study was designed to explore in detail the effect of this
      endocannabinoid on Ca2+ signaling in single cells of a calf pulmonary endothelial
      cell line. Anandamide initiated a transient Ca2+ elevation that was prevented by
      the CB2 receptor antagonist SR144528, but not by the CB1 antagonist SR141716A.
      These data were confirmed by molecular identification of the bovine CB2 receptor
      in these endothelial cells by partial sequencing. The phospholipase C inhibitor 1
      [6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole
      2,5dione and the inositol 1,4,5-trisphosphate receptor antagonist 2
      aminoethoxydiphenylborate prevented Ca2+ signaling in response to anandamide.
      Using an improved cameleon probe targeted to the endoplasmic reticulum (ER), fura
      2 and ratiometric-pericam, which is targeted to the mitochondria, anandamide was
      found to induce Ca2+ depletion of the ER accompanied by the activation of
      capacitative Ca2+ entry (CCE) and a transient elevation of mitochondrial Ca2+.
      These data demonstrate that anandamide stimulates the endothelial cells used in
      this study via CB2 receptor-mediated activation of phospholipase C, formation of
      inositol 1,4,5-trisphosphate, Ca2+ release from the ER and subsequent activation
      of CCE. Moreover, the cytosolic Ca2+ elevation was accompanied by a transient
      Ca2+ increase in the mitochondria. Thus, in addition to its actions on smooth
      muscle cells, anandamide also acts as a powerful stimulus for endothelial cells.

PMID- 14645145
TI  - Raised parenchymal interleukin-6 levels correlate with improved outcome after
      traumatic brain injury.
AB  - Previous studies have suggested that an increased production of the pro
      inflammatory cytokines interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) can
      influence patient outcome following a severe head injury. However, these studies
      have relied upon measurements of cytokine levels in CSF or serum, rather than the
      brain parenchyma itself. Recently, a method of intracranial microdialysis has
      been developed which permits the efficient recovery of macromolecules from the
      parenchyma. We have used this technique to investigate whether there is a
      correlation between patient outcome and parenchymally derived cytokines. Fourteen
      patients who were admitted to the Wessex Neurological Centre with severe head
      injury were selected for the study. This group of patients consisted of seven
      males and seven females with an age range of 21-77 years. Patients were treated
      according to standard protocols including emergency craniotomy where necessary.
      Microdialysis probes were implanted into the frontal region contralateral to the
      site of the primary injury. Approximately 200 micro l of dialysate was recovered
      every 8-12 h, and the concentrations of IL-6, IL-1beta and nerve growth factor
      (NGF) were determined by commercial enzyme-linked immunosorbent assays. Patients
      were assessed initially using the Glasgow coma score, and survivors were assessed
      after 6 months using the Glasgow outcome scale. Significantly (P = 0.04) higher
      levels of IL-6 were found in patients who survived compared with those who died.
      Also, there was a significant correlation between peak IL-6 levels and Glasgow
      outcome scores (r(2) = 0.34, P = 0.03, n = 14). The levels of IL-1beta and NGF
      were similar in both groups of patients. From these data, we suggest that IL-6 is
      an endogenous neuroprotective cytokine produced in response to severe head
      trauma.

PMID- 14645146
TI  - The basal ganglia and inhibitory mechanisms in response selection: evidence from
      subliminal priming of motor responses in Parkinson's disease.
AB  - Subliminal response priming was used to investigate inhibitory control processes
      relevant to response selection impairments in Parkinson's disease. Using a
      backward masking technique, covert activation of left- or right-hand responses
      was induced without subjects consciously perceiving the stimuli (right- or left
      pointing arrows). The masked priming stimuli were followed by visible arrow
      stimuli, instructing for a left- or right-hand response, at a delay
      (interstimulus interval, ISI) of 0 or 100 ms. Motor cortex activation was
      recorded by means of the electroencephalographic lateralized readiness potential
      (LRP). Parkinson's disease patients (n = 12) were compared with age-matched
      controls (n = 12) and young controls (n = 10). In young controls, the ISI = 100
      ms task effectively invoked inhibition of the subliminally primed responses, as
      demonstrated by a reversal of prime-target compatibility effects compared with
      the ISI = 0 ms task. This reversal implied that there was a so-called negative
      compatibility effect with faster responses and fewer errors when prime and target
      arrows pointed in opposite directions than when they required the same response.
      This negative compatibility effect turned into a positive compatibility effect in
      Parkinson's disease patients, while age-matched controls produced intermediate
      values. Together, these results support the view that response selection involves
      competitive, mutually inhibitory interactions between response alternatives,
      influenced by basal ganglia-thalamocortical mechanisms. As indicated by the
      reduced inhibition of partially activated responses, Parkinson's disease and, to
      a lesser degree, normal ageing affect the efficiency of these inhibitory
      interactions.

PMID- 14645147
TI  - Inhibitory functioning in Alzheimer's disease.
AB  - We present a comprehensive review of studies assessing inhibitory functioning in
      Alzheimer's disease. The objectives of this review are: (i) to establish whether
      Alzheimer's disease affects all inhibitory mechanisms equally, and (ii) where
      possible, to assess whether any effects of Alzheimer's disease on inhibition
      tasks might be caused by other cognitive deficits, such as slowed processing. We
      review inhibitory mechanisms considered to play a crucial role in various domains
      of cognition, such as inhibition involved in working memory, selective attention
      and shifting abilities, and the inhibition of motor and verbal responses. It was
      found that whilst most inhibitory mechanisms are affected by the disorder, some
      are relatively preserved, suggesting that inhibitory deficits in Alzheimer's
      disease may not be the result of a general inhibitory breakdown. In particular,
      the experimental results reviewed showed that Alzheimer's disease has a strong
      effect on tasks requiring controlled inhibition processes, such as the Stroop
      task. However, the presence of the disease appears to have relatively little
      effect on tasks requiring more automatic inhibition, such as the inhibition of
      return task. Thus, the distinction between automatic, reflexive inhibitory
      mechanisms and controlled inhibitory mechanisms may be critical when predicting
      the integrity of inhibitory mechanisms in Alzheimer's disease. Substantial
      effects of Alzheimer's disease on tasks such as negative priming, which are not
      cognitively complex but do require some degree of controlled inhibition, support
      this hypothesis. A meta-analytic review of seven studies on the Stroop paradigm
      revealed substantially larger effects of Alzheimer's disease on the inhibition
      condition relative to the baseline condition, suggesting that these deficits do
      not simply reflect general slowing.

PMID- 14645148
TI  - Why is parkinsonism not a feature of human methamphetamine users?
AB  - For more than 50 years, methamphetamine has been a widely used stimulant drug
      taken to maintain wakefulness and performance and, in high doses, to cause
      intense euphoria. Animal studies show that methamphetamine can cause short-term
      and even persistent depletion of brain levels of the neurotransmitter dopamine.
      However, the clinical features of Parkinson's disease, a dopamine deficiency
      disorder of the brain, do not appear to be characteristic of human
      methamphetamine users. We compared dopamine levels in autopsied brain tissue of
      chronic methamphetamine users with those in patients with Parkinson's disease and
      in a control group. Mean dopamine levels in the methamphetamine users were
      reduced more in the caudate (-61%) than in the putamen (-50%), a pattern opposite
      to that of Parkinson's disease. Some methamphetamine users had severely decreased
      dopamine levels, within the parkinsonian range, in the caudate (up to 97%
      dopamine loss) but not in the putamen. As the putamen and caudate subserve
      aspects of motor and cognitive function, respectively, our data suggest that
      methamphetamine users are not parkinsonian because dopamine levels are not
      sufficiently decreased in the motor component of the striatum. However, the near
      total reduction in the caudate could explain reports of cognitive disturbances,
      sometimes disabling, in some drug users, and suggests that treatment with
      dopamine substitution medication (e.g. levodopa) during drug rehabilitation might
      be helpful.

PMID- 14645150
TI  - IFN-alpha mediates the up-regulation of HLA class I on melanoma cells without
      switching proteasome to immunoproteasome.
AB  - Treatment of melanoma cell lines with IFN-gamma induces the switch from
      proteasome (PS) to immunoproteasome (iPS). This finding has profound implications
      for the immunobiology of melanoma cells since certain peptides (such as Melan
      A(mart1)(27-35)) are cleaved differently by iPS, thus implying a different
      ability to be presented by HLA class I molecules. IFN-alpha is a cytokine not
      only produced during infectious diseases, but also used in the treatment of
      certain cancers. Nevertheless, the effects of IFN-alpha on the switch of PS to
      iPS are largely unknown. A comparison of the effect of both IFN-alpha and IFN
      gamma was thus carried out on melanoma cell lines. RT-PCR showed that mRNA for
      iPS subunits (i.e. LMP-2, LMP-7 and MECL-1) was detectable both in untreated and
      IFN-treated melanoma cells. Immunoblotting analysis revealed that while IFN-gamma
      was able to consistently induce the switch from PS to iPS, IFN-alpha treatment
      did not, possibly due to post-transcriptional event(s) blocking the expression of
      iPS-specific subunits. Finally, Melan-A(mart1)(27-35) peptide was found only in
      the HPLC-MS spectra from both untreated and IFN-alpha-treated cells, but not upon
      IFN-gamma treatment. Altogether, these data demonstrate that IFN-alpha does not
      induce the switch from PS to iPS.

PMID- 14645149
TI  - Transforming growth factor-beta- and Activin-Smad signaling pathways are
      activated at distinct maturation stages of the thymopoeisis.
AB  - Members of the transforming growth factor (TGF)-beta family play pivotal roles in
      the control of differentiation, proliferation and tolerance in peripheral T
      cells. Recently, they have been implicated in thymic selection, but their role is
      so far not well characterized. In the present study, we demonstrate that specific
      thymocyte populations are under the influence of either the TGF-beta and/or
      Activin pathway, and transduce signals into the nucleus via phosphorylated Smad2
      (pSmad2). Thymocytes in the medulla and in the subcapsular zone expressed nuclear
      translocated pSmad2, a hallmark of active TGF-beta/Activin receptor signaling.
      When analyzed at the cellular level, the pSmad2(+) cells were confined to the
      double-negative (DN) and single-positive (SP) subpopulations. Moreover, the most
      immature DN thymocytes (CD44(+)CD25(-) and CD44(+)CD25(+)) expressed higher
      levels of pSmad2 compared to the more mature DN. In vitro stimulation
      demonstrated that pure CD44(+)CD25(-), CD44(+)CD25(+) and CD44(+)CD25(+)
      thymocytes respond to ActivinA, while the mature CD4(+) and CD8(+) SP thymocytes
      respond to TGF-beta stimulation measured as enhanced phosphorylation of Smad2.
      Double staining of pSmad2(+) cells with either the Activin type I receptor, ALK4,
      or the TGF-beta type I receptor, ALK5, demonstrated that pSmad2(+) DN cells
      exhibited high levels of immunoreactivity to ALK4 and moderate levels of
      immunoreactivity to the TGF-beta-responsive ALK5 receptor. In sharp contrast, the
      SP pSmad2(+) cells were predominately ALK5(+). Collectively, our results
      demonstrate that early and late thymocytes express pSmad2 in the nuclei in vivo.
      The functional experiments in vitro suggest that members of the TGF-beta family
      (TGF-beta or Activin) may play important non-redundant roles during different
      stages of thymopoiesis.

PMID- 14645151
TI  - Recombinant adenylate cyclase toxin of Bordetella pertussis induces cytotoxic T
      lymphocyte responses against HLA*0201-restricted melanoma epitopes.
AB  - The adenylate cyclase (CyaA) of Bordetella pertussis is able to deliver CD8(+) T
      cell epitopes into the cytosol of CD11b(+) dendritic cells (DC) following its
      specific interaction with the alpha(M)beta(2) integrin (CD11b/CD18). This
      delivery results in intracellular processing and presentation by MHC class I
      molecules of the CD8(+) T cell epitopes inserted into CyaA. Indeed, we previously
      showed that CyaA toxins carrying a single cytotoxic T lymphocyte (CTL) epitope
      can induce efficient protective and therapeutic antitumor immunity in mice. With
      a view to elaborating cancer immunotherapy in humans using CyaA, we constructed
      two recombinant CyaA carrying HLA*0201-restricted melanoma epitopes. Here we show
      that these recombinant CyaA induce strong anti-melanoma CTL responses in HLA*0201
      transgenic mice, even after a single i.v. immunization without adjuvant. These
      responses are long lasting, since they were also detected 5 months after the last
      injection. Finally, human DC treated with the recombinant CyaA were shown to
      process and present efficiently the melanoma epitopes to human CTL clones.
      Altogether, our results demonstrate that tumoral epitopes inserted into CyaA are
      efficiently processed and presented in association with human MHC molecules.
      These observations suggest that CyaA is capable of activating antitumoral CTL in
      humans and highlight the potential of CyaA for use in cancer immunotherapy.

PMID- 14645152
TI  - Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome
      protein-deficient mast cells.
AB  - Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in
      boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in
      signaling through the high-affinity IgE receptor (FcepsilonRI) using WASP
      deficient mice. IgE-dependent degranulation and cytokine secretion were markedly
      diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream
      signaling events that include FcepsilonRI-triggered total protein tyrosine
      phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk
      were not affected by WASP deficiency. However, tyrosine phosphorylation of
      phospholipase Cgamma and Ca(2+) mobilization were diminished. IgE-dependent
      activation of c-Jun N-terminal kinase, cell spreading and redistribution of
      cellular F-actin in mast cells were reduced in the absence of WASP. We conclude
      that WASP regulates FcepsilonRI-mediated granule exocytosis, cytokine production
      and cytoskeletal changes in mast cells.

PMID- 14645153
TI  - Differential implication of protein kinase C isoforms in cytotoxic T lymphocyte
      degranulation and TCR-induced Fas ligand expression.
AB  - CD8(+) cytotoxic T lymphocyte (CTL) clones are able to exert both perforin- and
      Fas-dependent cytotoxicity. We show in the present work that phosphatidylinositol
      3-kinase (PI3K) inhibitors wortmannin and LY294002 prevent TCR/CD3-induced
      functional Fas ligand (FasL) expression, but not perforin-dependent cytotoxicity.
      The specific inhibitor of classical protein kinase C (PKC) isoforms, Go6976,
      completely inhibited perforin-dependent cytotoxicity and only affected slightly
      TCR/CD3-induced FasL expression, while the opposite was observed using rottlerin,
      an inhibitor with higher specificity for PKCtheta. To address further the
      dependence of FasL expression on PI3K, a luciferase reporter controlled by the
      FasL promoter was used. Reporter gene induction by anti-CD3 mAb was abolished in
      cells transfected with dominant-negative PI3K (PI3K-DN) and increased in cells
      transfected with constitutively active PI3K (PI3K*). Transfection with
      constitutively active mutants (A/E) of PKCepsilon, and especially of PKCtheta,
      improved anti-CD3 mAb-induced reporter expression and completely abolished
      inhibition by wortmannin, while transfection with dominant-negative (K/R)
      PKCtheta prevented the induction of the reporter. Finally, transfection with
      PKCalpha A/E, but not with PKCtheta A/E, cooperated with ionomycin to induce
      degranulation in the CTL line 1.3E6SN. Altogether, the results suggest that
      TCR/CD3-induced FasL gene transcription is controlled by PI3K and PKCtheta
      activation, while this signaling pathway is not implicated in CTL degranulation,
      which is rather dependent on the activation of classical PKC isoforms.

PMID- 14645154
TI  - IL-10 regulates early IL-12-mediated immune responses induced by the radiation
      attenuated schistosome vaccine.
AB  - Radiation-attenuated (RA) schistosomes penetrate the host via the skin where they
      stimulate intense inflammatory reactions and the release of pro-inflammatory IL
      12, important for T(h)1-type immune responses which are partially host
      protective. However, RA larvae also induce the secretion of regulatory IL-10. We
      now show that following vaccination of IL-12p40(-/-) mice, abundant IL-10 was
      produced by in vitro cultured skin biopsies between days 4 and 14, corresponding
      to the down-regulation of MHC II expression by cells in the dermis and cells that
      emigrate from the skin. In IL-10(-/-) mice, inflammation of the vaccination site
      was increased with larger numbers of IL-12p40(+), MHC II(+) and CD86(+) cells in
      the dermal exudate, and was associated with elevated levels of skin-derived IL
      12p40 and IL-1beta. These changes in IL-10(-/-) mice were also reflected by an
      increased number of cells in the skin-draining lymph nodes (sdLN) and greater
      levels of lymphocyte proliferation. Moreover, such mice had increased numbers of
      CD4(+) sdLN cells that were CD25(+), CD28(+) or CD152(+) and accessory cells that
      were CD40(+) or MHC II(+). Finally, the secretion of IFN-gamma (and IL-12p40) by
      in vitro cultured sdLN cells was substantially raised in IL-10(-/-) mice, but
      much reduced in IL-12p40(-/-) mice, resulting in the development of highly
      polarized T(h)1 and T(h)2 cytokine profiles in the two groups of mice
      respectively. We conclude that IL-10 has an important role early in the
      regulation of IL-12-mediated priming of acquired immune responses, and
      effectively contains excessive dermal inflammation and prevents the development
      of highly polarized T(h)1-type responses.

PMID- 14645155
TI  - Decreased CD154 expression by neonatal CD4+ T cells is due to limitations in both
      proximal and distal events of T cell activation.
AB  - Neonatal CD4(+) T cells express less CD154 protein and mRNA than adult CD4(+) T
      cells after activation by calcium ionophore and phorbol ester, but the mechanism
      for this reduced expression and its relevance to the primary immune response
      remain unclear. We compared expression of CD154 protein and mRNA and CD154 gene
      promoter activity by purified naive (CD45RA(high)CD45RO(low)) neonatal and adult
      CD4(+) T cells after activation by calcium ionophore (ionomycin) and phorbol
      myristate acetate (PMA) treatment or by engagement of alphabeta TCR-CD3 complex.
      Substantial and consistent reductions in expression by neonatal cells were found
      in all cases and were paralleled by decreased CD154-dependent activation of a B
      cell line. CD69 expression by neonatal CD4(+) T cells after alphabeta TCR-CD3
      engagement was also reduced compared to adult cells, which suggested that
      limitations in activation-induced signaling by neonatal CD4(+) T cells occurred
      at a point upstream of where the signaling pathways leading to CD154 and CD69
      expression diverge. Decreased CD154 expression by neonatal cells after alphabeta
      TCR-CD3 engagement was paralleled by a lower free intracellular calcium
      concentration, a key event for CD154 gene transcription. Reduced CD154 promoter
      activity by neonatal cells persisted when proximal signaling events were bypassed
      using ionomycin and PMA, suggesting an additional and more distal mechanism for
      decreased transcription. In contrast, CD154 mRNA stability was similar in
      neonatal and adult cells after either ionomycin and PMA stimulation or engagement
      of the alphabeta TCR-CD3 complex. We conclude that decreased CD154 production by
      neonatal CD4(+) T cells is due to limitations in both proximal and distal
      activation events, which together ultimately limit CD154 gene transcription.

PMID- 14645156
TI  - Autoantibodies and CD4 T cells target a beta cell retroviral envelope protein in
      non-obese diabetic mice.
AB  - We determined that, over a biologic time interval, from 4 to 8 weeks of age,
      female non-obese diabetic (NOD) mice develop antibodies against pancreatic beta
      cell-surface antigens depending upon the presence of both the MHC class II
      susceptibility allele, I-A(g7), and other NOD background genes. We generated a
      mAb from a pre-diabetic NOD mouse that binds to the surface of insulinoma cells
      and isolated mouse beta cells, and identified the target as a retroviral envelope
      glycoprotein expressed on pancreatic beta cells. The cloned and expressed
      sequence for this protein was recognized by the mAb. The antibody as well as sera
      from pre-diabetic NOD mice recognized the recombinant protein. Spontaneous T cell
      reactivity against a peptide from the cloned protein was found in NOD mice. In
      conclusion, a beta cell retroviral envelope protein is a target antigen that is
      selected by the NOD mouse immune system early in the pathogenesis of autoimmune
      diabetes.

PMID- 14645157
TI  - beta-Catenin expression enhances generation of mature thymocytes.
AB  - T cell factor (TCF)-1 is a T-cell-specific transcription factor that is expressed
      at all stages of T cell development. Deletion of the TCF-1 gene leads to an early
      block in thymocyte maturation precluding the study of its role at late stages and
      during positive selection of T cells. In this report we show that beta-catenin, a
      central effector in the Wnt-TCF-1 signaling pathway, regulates late stages of T
      cell development. Specifically, transgenic expression of beta-catenin enhances
      generation of mature thymocytes. Interestingly, CD8-expressing mature thymocytes
      were affected to a greater extent than CD4-expressing cells. These data suggest
      that the Wnt-beta-catenin-TCF-1 signaling pathway plays a role during late stages
      of T cell development.

PMID- 14645158
TI  - Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell
      proliferation without modulating the cytokine response.
AB  - Transforming growth factor (TGF)-beta has been demonstrated to play a key role in
      the regulation of the immune response, mainly by its suppressive function towards
      cells of the immune system. In humans, the effect of TGF-beta on antigen-specific
      established memory T cells has not been investigated yet. In this study antigen
      specific CD4(+) T cell clones (TCC) were used to determine the effect of TGF-beta
      on antigen-specific proliferation, the activation status of the T cells and their
      cytokine production. This study demonstrates that TGF-beta is an adequate
      suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle
      rate rather than induction of apoptosis. Addition of TGF-beta resulted in
      increased CD69 expression and decreased CD25 expression on T cells, indicating
      that TGF-beta is able to modulate the activation status of in vivo differentiated
      T cells. On the contrary, the antigen-specific cytokine production was not
      affected by TGF-beta. Although TGF-beta was suppressive towards the majority of
      the T cells, insensitivity of a few TCC towards TGF-beta was also observed. This
      could not be correlated to differential expression of TGF-beta signaling
      molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and
      Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary,
      TGF-beta has a pronounced inhibitory effect on antigen-specific T cell
      proliferation without modulating their cytokine production.

PMID- 14645159
TI  - Clinical as well as statistical knowledge is needed when determining how
      subfertility trials are analysed.

PMID- 14645162
TI  - Is there a future for ovulation induction in the current era of assisted
      reproduction?
AB  - The clinical use of medical induction of ovulation in normogonadotrophic
      anovulatory women (WHO II), including polycystic ovary syndrome, is increasingly
      questioned. However, we believe that this treatment modality still represents a
      highly effective means of fertility treatment in women with low pregnancy chances
      without intervention. A conventional treatment algorithm involving clomiphene
      citrate (CC) followed by FSH induction of ovulation may result in a 71%
      cumulative singleton live birth rate. In attempts to improve treatment outcome
      further and reduce complication rates, new compounds such as insulin-sensitizing
      agents or aromatase inhibitors are currently used increasingly. Approaches such
      as patient selection for different treatment modalities on the basis of initial
      screening characteristics and alternative protocols for FSH ovulation induction
      may also be proposed to render treatment algorithms more patient tailored and
      therefore improve overall outcomes. More research is needed in this area, rather
      than referring these patients to assisted reproduction prematurely. This may lead
      to a more individually tailored approach for ovulation induction in a given
      patient, resulting in a further improvement of the balance between chances for
      success versus complications.

PMID- 14645163
TI  - Reactive oxygen species and adhesion formation: clinical implications in adhesion
      prevention.
AB  - Postoperative adhesion formation is a major clinical problem. It has been
      demonstrated that the pneumoperitoneum used during laparoscopy is a cofactor in
      adhesion formation. Reactive oxygen species (ROS) are produced in a hyperoxic
      environment and during the ischaemia/reperfusion process. ROS activity is
      deleterious for cells, which protect themselves by an antioxidant system known as
      ROS scavengers. ROS activity can increase by up-regulation of ROS themselves or
      by down-regulation of ROS scavengers. Recent data also point to a role for ROS in
      adhesion formation since the administration of ROS scavengers decreases adhesion
      formation in several animal models. ROS activity increases during both laparotomy
      and laparoscopy. During laparoscopy, the pneumoperitoneum determines ischaemia at
      the time of insuflation and reperfusion at the time of deflation. During
      laparotomy, the environment has a 150 mmHg partial pressure of oxygen (pO(2)),
      which is much higher than the intracellular pO(2) (5-40 mmHg). This can explain
      the increase in ROS activity. The aim of this debate is to open a discussion
      about the importance of ROS activity, besides the known players and mechanisms
      involved, in adhesion formation and in adhesion prevention.

PMID- 14645164
TI  - Epigenetic risks related to assisted reproductive technologies: epigenetics,
      imprinting, ART and icebergs?
AB  - Recently, a series of case reports and small studies has suggested that births
      involving assisted reproductive technology (ART) may have an increased risk of
      imprinting disorders such as Beckwith-Wiedemann syndrome and Angelman syndrome.
      Herein, the significance and implications of these findings are discussed. It is
      speculated that, although such imprinting disorders may be shown to be only rare
      complications of ART, epigenetic errors might account for a much wider spectrum
      of ART-related complications than is recognized currently. Addressing these
      questions should be a priority for research on cohorts of ART children.

PMID- 14645165
TI  - Menopause in crisis post-Women's Health Initiative? A view based on personal
      clinical experience.
AB  - Menopausal women should not consider that hormonal treatment is an obligatory
      long-term commitment. Estrogen-based treatments are extremely effective for
      vasomotor symptom relief and for vaginal atrophy. HRT also is one of several
      effective methods for the primary prevention of osteoporosis. If trials were done
      early after the menopause when the endothelium is likely still to be intact,
      estrogen-based treatment might be shown to prevent coronary heart disease.
      However, greater efficacy is to be expected from smoking cessation, proper
      nutrition, exercise, moderate alcohol consumption, statins, beta-blockers and
      angiotensin-converting enzyme inhibitors. The treatment options for a menopausal
      woman should include non-drug-related strategies, non-hormonal pharmaceutical
      therapies as well as hormonal treatments. The first objective of this
      contribution is to call to the attention of practising physicians the fact that
      the Women's Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement
      Study (HERS) studies involved women much older than the early postmenopausal age
      groups for whom HRT is prescribed because of symptoms. The second objective is to
      emphasize that the attending physicians must not only treat the symptomatic women
      but also prevent the occurrence of diseases more prevalent after 60 years of age.
      Hormones can safely be used for the former, when not contraindicated, whereas for
      the latter non-pharmacological interventions and non-hormonal medications are
      preferable.

PMID- 14645166
TI  - Mast cell-sperm interaction: evidence for tryptase and proteinase-activated
      receptors in the regulation of sperm motility.
AB  - BACKGROUND: The detection of significant levels of tryptase in human seminal
      plasma and follicular fluid and of tryptase-positive mast cells (MCs) in the wall
      of human Fallopian tubes lead us to hypothesize that tryptase may exert
      regulatory actions on human spermatozoa. METHODS AND RESULTS:
      Immunoelectronmicroscopy revealed proteinase-activated receptor 2 (PAR-2) in the
      membranes of the acrosomal region and midpiece of human spermatozoa. These PAR-2
      were functional, as exposure of spermatozoa from healthy men (n = 12) with
      regular standard semen parameters to human recombinant tryptase significantly
      decreased motility in a dose- and time-dependent fashion. Motile spermatozoa (WHO
      a + b) were significantly decreased within 10 min of incubation with 1.000 ng/ml
      tryptase (P = 0.045). After 30 and 60 min, significant reduction of motility was
      also observed in the presence of lower tryptase concentrations (100 ng/ml, P =
      0.037; 10 ng/ml, P = 0.046). The inhibitory effects of tryptase progressed
      throughout an observation period of 180 min. Furthermore, tryptase effects were
      reversible after washing procedures and could be inhibited by pretreatment with
      anti-tryptase antibody or anti-PAR-2 antiserum. CONCLUSIONS: The observations
      presented raise the possibility that tryptase directly interacts with human
      spermatozoa during their migration through the female genital tract. Genital
      tract MCs and their products may be as yet unrecognized factors involved in human
      fertility/sterility.

PMID- 14645167
TI  - Lack of an association between environmental exposure to polychlorinated
      biphenyls and p,p'-DDE and DNA damage in human sperm measured using the neutral
      comet assay.
AB  - BACKGROUND: Chlorinated organic chemicals, such as polychlorinated biphenyls
      (PCB), hexachlorobenzene (HCB), dichlorodiphenyl trichloroethane (DDT), and
      dichlorodiphenyl dichloroethene (DDE, the most stable daughter compound of DDT)
      are persistent lipophilic compounds found in a large portion of the general
      population. To explore the hypothesis that environmental exposure to these
      compounds is associated with altered DNA integrity in human sperm, a study of 212
      male partners of a sub-fertile couple who presented to the Massachusetts General
      Hospital Andrology Laboratory was conducted. METHODS: The neutral single cell
      microgel electrophoresis assay (comet assay) was used to assess DNA integrity in
      sperm. VisComet image analysis software was used to measure total comet length,
      the proportion of DNA present in the comet tail, and tail distributed moment, an
      integrated measure of length and intensity. RESULTS: In the regression analyses,
      there were no statistically significant consistent associations between the comet
      assay parameters and any of the individual PCB congeners, sum of PCB, or p,p'
      DDE. CONCLUSION: These results suggest that there are not strong relationships
      between adult levels of these chlorinated organic compounds and sperm DNA damage
      as measured by the comet assay.

PMID- 14645168
TI  - Testicular sperm extraction in azoospermic men submitted to bilateral
      orchidopexy.
AB  - BACKGROUND: This study was carried out to evaluate whether bilateral orchidopexy
      represents a poor or good prognostic factor in azoospermic men undergoing
      testicular sperm extraction (TESE). METHODS: One hundred and seven presumed non
      obstructive azoospermia (NOA) patients, according to conventional clinical
      parameters (volume of testis, FSH, clinical history) were submitted to testicular
      biopsy with TESE. Thirty men (28%) had a history of bilateral orchidopexy for
      cryptorchidism. RESULTS: Normal spermatogenesis or mild hypospermatogenesis was
      diagnosed in 12/30 ex-cryptorchid patients and in 7/77 presumed NOA patients (P =
      0.0004). Conversely, pure Sertoli cell-only syndrome or complete maturation
      arrest was found in 10/30 ex-cryptorchid patients and in 48/77 presumed NOA
      patients (P = 0.0094). In 53/107 patients (49.5%), TESE allowed a positive sperm
      retrieval. At least one spermatozoon was observed in 22/30 ( approximately 73%)
      ex-cryptorchid patients and in 31/77 ( approximately 40%) presumed NOA patients
      (P = 0.0026). A large number of spermatozoa (equivalent to an obstructive
      pathology) were retrieved in 13/30 ex-cryptorchid and in 10/77 presumed NOA
      patients (P = 0.001). A history of bilateral orchidopexy in presumed NOA patients
      correlates positively for the chance of retrieving testicular spermatozoa (odds
      ratio 3.8; 95% confidence interval 1.41-10.21; P = 0.008). CONCLUSIONS: Although
      bilateral cryptorchidism is usually considered a testicular secretive
      dysfunction, TESE permits retrieval of a large number of spermatozoa in almost
      40% of cases. Our data suggest the existence of congenital or acquired
      obstructive anomalies of the seminal ducts in azoospermic orchidopexed men.

PMID- 14645169
TI  - Thromboelastography, whole-blood haemostasis and recurrent miscarriage.
AB  - BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis.
      Thromboelastography is a rapid, reproducible test of whole-blood haemostasis.
      METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women
      (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks
      gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range
      20-41) with no history of pregnancy loss. The prospective outcome of untreated
      pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS:
      The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was
      significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5
      7.8) significantly lower amongst women with recurrent miscarriage compared with
      controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P =
      0.01). The pre-pregnancy MA was significantly higher amongst women who
      subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those
      whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA
      >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage.
      CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent
      miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a
      state are at increased risk of miscarriage in future untreated pregnancies.

PMID- 14645170
TI  - Glycosaminoglycans and proteoglycans in the skin of aneuploid fetuses with
      increased nuchal translucency.
AB  - BACKGROUND: First trimester increased fetal nuchal translucency is associated
      with fetal aneuploidies. One of the mechanisms of pathophysiology could be an
      abnormal extracellular matrix facilitating the formation of an interstitial
      edema. A previous study investigating interstitial edema in first trimester
      fetuses found large amounts of hyaluronan in the skin of fetuses with trisomy 21.
      The aim of this study was to establish distribution patterns for a number of
      other glycosaminoglycans-dermatan, heparan and keratan sulphate, chondroitin-6
      sulphate and chondroitin-4-sulphate proteoglycan-in the nuchal skin of normal and
      chromosomally abnormal fetuses at 11-14 weeks. We also investigated whether
      biglycan (BGN), which is located on chromosome X, is underexpressed in fetuses
      with Turner syndrome. Decorin (DCN), a similar-sized proteoglycan located on
      chromosome 12, was taken as a control. METHODS: We studied the distribution and
      concentration of various extacellular matrix components using
      immunohistochemistry, a double staining technique, in-situ hybridization,
      Northern and Western blot analysis. RESULTS: Chondroitin-6-sulphate and
      chondroitin-4-sulphate proteoglycan were increased in Turner syndrome fetuses and
      BGN seemed to be underexpressed compared with normal controls, while DCN was not.
      Dermatan, heparan and keratan sulphate showed no significant abnormal
      distribution in trisomies 21, 18, 13, or in Turner syndrome, compared with
      normal. Western and immunohistochemical analysis revealed that absence of a
      second X chromosome, as is the case in Turner syndrome, affects BGN protein
      pattern. CONCLUSIONS: An abnormal amount of glycosaminoglycans and proteoglycans
      presumably contributes to increased nuchal translucency.

PMID- 14645171
TI  - Successful pregnancy outcome following 19 consecutive miscarriages: case report.
AB  - No cause can be found in 50% of patients with recurrent miscarriage. Recent
      research has shown that high levels of natural killer (NK) cells within the
      endometrium may be associated with idiopathic recurrent miscarriage. This case
      report describes a patient in whom an excessive number of uterine NK cells were
      found. She received preconceptual prednisolone and delivered a live baby. This is
      a novel observation of untested significance.

PMID- 14645172
TI  - Chromosomally abnormal cells are not selected for the extra-embryonic compartment
      of the human preimplantation embryo at the blastocyst stage.
AB  - BACKGROUND: Although well defined for embryos at cleavage stages, the occurrence
      and frequency of chromosomal aberrations in human blastocysts is relatively
      unknown. It has been reported that only one in four blastocysts is comprised
      totally of chromosomally normal cells. One of the selection mechanisms for the
      embryo proper to become free of these chromosomally abnormal cells would be to
      sequester them to the extra-embryonic compartment during development. The study
      aim was to investigate whether such a mechanism of selection exists in human
      preimplantation embryos. METHODS: Inner cell mass (ICM)/trophectoderm (TE)
      differentiation was performed, followed by fluorescence in-situ hybridization
      (FISH), to study the chromosomal distribution in both populations of cells.
      RESULTS: Of the 94 successfully analysed blastocysts, 68.8 +/- 1.5% of all
      analysable nuclei per blastocyst showed a disomic chromosomal content. Only 22.6%
      of blastocysts analysed were classified as normal. Of the embryos classified as
      abnormal at the blastocyst stage, 11.9% showed a simple mosaic pattern and 32.1%
      a complex mosaic pattern. An equally large group of blastocysts showed either a
      chaotic pattern (16.7%), or the chromosomal pattern could not be classified. The
      average degree of normal cells in the ICM (67.9%) was similar to the degree
      observed in the TE (69.5%). CONCLUSIONS: These findings indicate that
      chromosomally abnormal cells are not preferentially segregating to the extra
      embryonic compartment of the human preimplantation embryo at the blastocyst
      stage. Hence, other mechanisms should be responsible for an absence of
      chromosomally abnormal cells in the embryo proper at later stages of development.
      One possible mechanism might be the elimination of the chromosomally abnormal
      cells by selective cell death activation.

PMID- 14645173
TI  - FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of
      IVF pre-embryos from 144 randomly selected donated human oocytes and impact on
      pre-embryo morphology.
AB  - BACKGROUND: The data are compiled from two multicentre, prospectively randomized
      studies on the effect of follicular fluid meiosis-activating sterol (FF-MAS) on
      human oocytes. The donated oocytes were exposed either to test doses of FF-MAS or
      to control solutions. The data from the control groups are presented with
      chromosomal status of the embryos correlated to embryo morphology. METHODS: The
      study includes 144 randomly selected donated human oocytes. The nucleus from each
      blastomere was fixed separately and fluorescence in-situ hybridization (FISH)
      using seven probes (13, 16, 18, 21, 22, X and Y) was performed. RESULTS: Analysis
      of 103 pre-embryos containing 479 blastomeres resulted in 424 blastomeres with
      clear FISH signals. Of these blastomeres, 55% were normal diploid and 45% were
      abnormal. At a pre-embryonic level, 53% were classified as normal containing
      >or=50% normal blastomeres while 31% of the pre-embryos were classified as
      uniformly normal. Abnormality rate was significantly increased in the pre-embryos
      with unevenly sized blastomeres and with increasing degree of fragmentation at 68
      h after fertilization. Applying criteria for good embryo quality significantly
      increased the rate of chromosomally normal pre-embryos from 53 to 75%.
      CONCLUSIONS: The data demonstrate the high degree of genetic heterogeneity in a
      randomly selected pool of donated pre-embryos from an IVF programme. Further, we
      found that uniformity of blastomere size, degree of fragmentation and cleavage
      kinetics reflect the cytogenetic status of the pre-embryo and are therefore
      important in the selection of pre-embryos.

PMID- 14645174
TI  - Prostacyclin enhances embryo hatching but not sperm motility.
AB  - BACKGROUND: Recently we discovered that the human oviduct synthesizes abundant
      prostacyclin (PGI(2)). Gene knock-out studies suggest that PGI(2) is essential to
      endometrial decidualization, but the effects of PGI(2) on sperm and embryos have
      not been reported. METHODS: The effects of PGI(2) on human sperm were analysed by
      a computer-assisted semen analysis system. The effects of PGI(2) on mouse embryos
      were examined based on the rates of complete hatching. The expression of PGI(2)
      receptor (IP) was evaluated by Western blot analysis and immunohistochemistry.
      The binding of PGI(2) to embryos was confirmed by radioligand binding assay.
      Finally, cAMP levels were assessed in PGI(2)-challenged embryos. RESULTS:
      Iloprost (a stable PGI(2) analogue) did not affect the motility or the overnight
      survivability of human sperm. Western blot analysis did not detect IP in the
      sperm plasma membrane. In contrast, the hatching of mouse embryos was enhanced by
      iloprost (ED(50) 6.7 nmol/l). Exposure to iloprost during 8-cell to morulae or
      morulae to early blastocyst stages was critical to enhanced hatching. This
      coincided with the developmental stage-specific expression of IP. Although
      iloprost bound to blastocysts, it did not significantly increase cAMP.
      CONCLUSION: PGI(2) enhanced the hatching of mouse embryos but not the motility of
      human sperm.

PMID- 14645175
TI  - Early outcome of myomectomy by laparotomy, minilaparotomy and laparoscopically
      assisted minilaparotomy. A randomized prospective study.
AB  - BACKGROUND: To compare in the first 7 days after surgery the outcome of
      myomectomy performed by three laparotomic approaches: laparotomy (LT),
      minilaparotomy (MLT) and laparoscopically assisted minilaparotomy (LA-MLT).
      METHODS: Fifty-one women with 5-15 cm total myoma diameter were randomized
      blindly using a computer randomization list, to LT (n = 17), MLT (n = 17) or LA
      MLT (n = 17). RESULTS: Mean operation length was similar in the three groups.
      Mean (+/- SEM) time of paralytic ileus (55.0 +/- 4.5 versus 33.4 +/- 3.4 h; P <
      0.01) and discharge (141.6 +/- 5.2 versus 81.5 +/- 8.2 h; P < 0.01) was longer in
      LT than LA-MLT or even MLT. In comparison with LA-MLT, LT induced a greater
      haemoglobin decline (-3.07 +/- 0.3 versus -1.8 +/- 0.15 mg/dl; P < 0.025), and a
      greater post-operative stress, as documented by increased prolactin (+15.1 +/-
      3.8 versus +0.16 +/- 4.5 ng/ml; P < 0.03) and decreased insulin sensitivity
      (fasting glucose/insulin; -7.5 +/- 2.6 versus -0.7 +/- 2.1; P < 0.02). Seven days
      after surgery, abdominal pain (P < 0.05) was higher after LT (3.0 +/- 0.6) than
      MLT (0.5 +/- 0.2) and LA-MLT (0.9 +/- 0.4). CONCLUSIONS: In selected cases,
      myomectomy by LA-MLT offers some advantages versus LT and, to a smaller extent,
      MLT.

PMID- 14645176
TI  - Women with endometriosis have increased levels of placental growth factor in the
      peritoneal fluid compared with women with cystadenomas.
AB  - BACKGROUND: To assess the release of placental growth factor (PlGF) into
      peritoneal fluid in women with and without endometriosis, we measured its
      concentration with reference to disease stage, the presence of red endometriotic
      lesions and the phase of menstrual cycle. METHODS: Surgery was scheduled in the
      proliferative or secretory phase of the menstrual cycle for 59 women with (n =
      35) or without (n = 24) endometriosis. The latter group comprised women
      undergoing surgery for ovarian cystadenomas. PlGF concentrations in the
      peritoneal fluid were measured using an enzyme-linked immunosorbent assay.
      RESULTS: PlGF concentration in the peritoneal fluid was markedly elevated in the
      endometriosis patients (median 189 pg/ml, interquartile range 84-475 pg/ml) as
      compared with the controls (88 pg/ml, 41-213 pg/ml; P < 0.001), especially in
      women with red lesions. Significantly greater values during the secretory phase
      of the menstrual cycle as compared with the proliferative phase were observed in
      both the control (cystadenoma) group (P < 0.05) and the endometriosis group (P <
      0.001). CONCLUSIONS: Our findings suggest that production of PlGF is sensitive to
      the cyclic changes in ovarian steroids and may contribute to the pathogenesis of
      endometriosis, especially that of red lesions, by promoting neovascularization.

PMID- 14645177
TI  - Minimal surgery for the twisted ischaemic adnexa can preserve ovarian function.
AB  - BACKGROUND: Recently detorsion has replaced salpingo-oophorectomy as treatment
      for the twisted ischaemic adnexa. This paper asssess whether the ovary resumes
      normal function after preservation by detorsion. METHODS: The results of
      detorsion performed between January 1988 and December 2001 were retrospectively
      analysed. Post-operative complications and subsequent ovarian function were
      assessed including: ultrasound monitoring of follicular development, adnexal
      appearance during subsequent surgery, and the outcome of IVF. RESULTS: A total of
      102 detorsions were performed; 67 by laparoscopy, 35 by laparotomy. No patient
      developed thromboembolism. Post-operative fever occurred in 15% of patients after
      laparoscopy and 29% after laparotomy (P < 0.01). Patients were hospitalized for a
      mean (+/- SD) of 2.1 +/- 1.2 and 7.4 +/- 1.5 days after laparoscopy and
      laparotomy respectively (P < 0.001). Ultrasound showed normal follicular
      development in 93 and 91% of patients after detorsion by laparoscopy and
      laparotomy respectively. At subsequent surgery, the adnexa appeared normal in
      nine out of nine patients after laparoscopy and in four out of five patients
      after laparotomy. Four patients of the laparoscopy group and two patients of the
      laparotomy group underwent subsequent IVF. In all six patients oocytes retrieved
      from the previously ischaemic ovary were fertilized. CONCLUSIONS: Detorsion with
      adnexal sparing is the treatment of choice for twisted ischaemic adnexa, and
      preferably performed by laparoscopy.

PMID- 14645178
TI  - In-vitro and in-vivo histochemical and thermal studies using a thermal balloon
      endometrial ablation system for varying treatment times.
AB  - BACKGROUND: To assess the immediate zone of thermal necrosis (ZTN) using an
      enzyme histochemical staining technique and serosal temperatures for the Cavaterm
      endometrial balloon ablation system for different treatment times. METHODS: A
      thermal balloon ablation was performed initially post- (n = 6) and subsequently
      pre-hysterectomy (n = 15). Eight to 12 tissue blocks from each uterus were
      sectioned and stained using diaphorase respiratory enzyme techniques. Patients in
      the in-vivo group had temperature measurements taken from four serosal points, a
      myometrial gradient profile, the balloon surface and the endocervical canal.
      RESULTS: The serosal temperature sensors did not demonstrate any rise in
      temperature above 44.1 degrees C. The mean temperature at the anterior wall,
      posterior wall, fundus and cornual areas was 37.1 (SD 1.3), 36.8 (SD 1.0), 37.4
      (SD 1.8) and 36.7 degrees C (SD 1.0), respectively. The immediate mean maximum
      ZTN was greatest for the 15-min treatment time (3.1 mm, SD 1.5) compared to the
      10- and 7-min treatment times (3.0 mm, SD 1.4 and 2.2 mm, SD 0.7, respectively).
      The maximum ZTN recorded was 5.6 mm. No full thickness injuries were demonstrated
      either histochemically or suggested by the temperature studies. CONCLUSIONS: This
      study confirms that Cavaterm thermal balloon ablation produces a reproducible
      thermal injury without evidence of serosal heating. Results suggest that the
      treatment time could be reduced to 10-min with no detrimental effect on the
      clinical outcomes. This hypothesis is currently being evaluated by clinical
      trials.

PMID- 14645179
TI  - Unsuspected pregnancy at hysterosalpingography: a report of three cases with
      different outcomes.
AB  - We report three cases of unsuspected pregnancy during hysterosalpingography (HSG)
      with different outcomes. In the first two cases, menstrual history was wrongly
      relied upon and no pregnancy tests had been performed. However, even with a
      negative pregnancy test carried out prior to the investigation, as in the third
      case, this was proven not to be foolproof. The outcome of our pregnancies
      involves one ectopic, one miscarriage and one normal term pregnancy. We advocate
      not relying solely on menstrual history and to be aware that even in cases where
      there is a negative pregnancy test before HSG, the patient can still be pregnant.
      Although the reporting of unsuspected pregnancy during HSG is rare, there is
      still a need to be alert, especially in high-risk patients with irregular, long
      menstrual cycles and unprotected intercourse prior to the investigation.

PMID- 14645180
TI  - Local levonorgestrel regulation of androgen receptor and 17beta-hydroxysteroid
      dehydrogenase type 2 expression in human endometrium.
AB  - BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is a
      highly effective contraceptive. However, unscheduled breakthrough bleeding (BTB),
      leads to discontinuation in a proportion of users. The LNG-IUS down-regulates
      endometrial progesterone and estrogen receptors and this may play a role in the
      mechanism responsible for BTB. LNG is an androgenic progestogen and so we
      examined the regulation of the androgen receptor (AR) in endometrium exposed to
      intrauterine LNG. Furthermore, as the enzyme 17beta-hydroxysteroid dehydrogenase
      type 2 (17betaHSD2) regulates intracellular levels of estrogens, progestins and
      androgens, we evaluated the changes in expression of 17betaHSD2 in the same
      tissue endometrial samples. METHODS: Immunohistochemistry and real time
      quantitative RT-PCR were used to compare protein and mRNA expression of AR and
      17betaHSD2 in endometrial biopsies from women with normal menstrual cycles and
      those using a LNG-IUS. RESULTS: Immunohistochemistry showed that AR and
      17betaHSD2, which were immunolocalized to the stroma and glands of endometrium
      respectively, were both suppressed by LNG-IUS treatment, though moderate staining
      of 17betaHSD2 was evident 1 month after insertion of the LNG-IUS. AR mRNA
      expression was down-regulated in LNG-exposed endometrium when compared with the
      proliferative phase of the menstrual cycle. 17betaHSD2 mRNA was significantly
      increased 3 months (but not 6-12 months) after LNG-IUS insertion. CONCLUSIONS:
      Endometrial intracellular estradiol levels would have been suppressed by
      17betaHSD2 during the first few, but not the later, months of LNG-IUS action, and
      the lowered endometrial estradiol level may contribute to the frequent BTB
      evident in the early months of LNG-IUS use. The subsequent decline in 17betaHSD2
      would lead to elevated local intracellular estradiol in the later months, when
      the BTB tends to subside. The suppression of AR by the LNG-IUS may also play a
      role in BTB, as elevated AR has been associated with amenorrhoea.

PMID- 14645181
TI  - Cervical dilatation with hygroscopic rods prior to ovarian stimulation
      facilitates embryo transfer.
AB  - BACKGROUND: Embryo transfer is a critical factor affecting the success of IVF-the
      ease of embryo transfer has a direct impact on the success rate. The aim of this
      study was to assess the value of cervical dilatation with hygroscopic cervical
      rods (Dilapan-S) in patients with difficult embryo transfer. METHODS: Fifty-four
      patients undergoing IVF treatment, who either failed to conceive after previous
      difficult embryo transfer or were noted to have difficult mock embryo transfer
      were retrospectively included in the study. In this way the patients acted as
      control for themselves. The Dilapan-S rods were placed intracervically and left
      for 4 h prior to starting gonadotrophin stimulation as an outpatient procedure.
      RESULTS: Of the 54 patients who originally had difficult embryo transfer, 43
      patients (79.5%) had subsequent easy embryo transfer. Thirty patients managed to
      conceive, giving a clinical pregnancy rate of 55%. CONCLUSIONS: Cervical
      dilatation using hygroscopic dilators facilitates difficult embryo transfer and
      helps to improve the pregnancy rate.

PMID- 14645182
TI  - Performance of five serological chlamydia antibody tests in subfertile women.
AB  - BACKGROUND: Micro-immunofluorescence (MIF) is widely used for chlamydia antibody
      testing (CAT). Recently a species-specific MIF and three enzyme-linked
      immunosorbent assay (ELISA) tests have been introduced. We compared five
      commercially available CAT tests, using laparoscopy as a reference, and evaluated
      whether combinations of tests could improve the predictive value of CAT. METHODS:
      In a consecutive cohort of 315 subfertile women, results of the five CAT tests
      were correlated to findings at laparoscopy. Likelihood and odds ratios (OR) were
      calculated for single tests and for combinations of tests. RESULTS: Of the tests
      evaluated, MIF Labsystems had the best diagnostic performance (OR 15.7), while
      pELISA Medac (OR 8.2) was the best of the three ELISA tests. Stepwise logistic
      regression analysis showed that performance of MIF Labsystems could not be
      improved by adding a second test. Significant cross-reactivity with C. pneumoniae
      antibodies was found in all tests evaluated, except in pELISA Medac. CONCLUSIONS:
      In screening for tubal factor subfertility, MIF Labsystems was superior to the
      ELISA tests evaluated, and combining two CAT tests did not improve its predictive
      value. Economic analysis will show whether serial testing by pELISA Medac, and
      retesting positive samples by MIF Labsystems, is most cost-effective. In CAT,
      cross-reactivity with C. pneumoniae antibodies is still a major concern.

PMID- 14645183
TI  - Estimated maximum failure rates of cycle monitors using daily conception
      probabilities in the menstrual cycle.
AB  - BACKGROUND: A number of menstrual cycle monitors have been developed to detect
      the fertile window of the menstrual cycle, mainly for contraceptive purposes.
      Reliable data on most of these systems are still missing but are urgently needed
      because many women use them and the tested systems differ enormously in price and
      effectiveness. We suggest a new efficacy estimating method to evaluate cycle
      monitors prior to full prospective clinical trials. METHODS: Sixty-two women
      prospectively tested seven cycle monitors and the symptothermal method (STM) of
      natural family planning (NFP) but not more than two different systems at the same
      time. The clinical fertile window was determined by detecting the day of
      ovulation using daily urinary LH measurements and daily ultrasonic
      folliculometry. This was compared to the fertile phase predicted by the systems.
      Maximum failure rates were estimated for each cycle monitor and the STM, using
      the daily conception probability rates taken from the European Fecundability
      Study. Intercourse was assumed to occur on each of all falsely predicted days of
      infertility. RESULTS: Sixty-two women with a mean age of 31 years (range: 21-42
      years) contributed a total of 122 cycles to this study. Monitors based on the
      microscopic evaluation of saliva or mucus had many more false infertile days than
      the other methods based on temperature or hormonal measurements (225 versus 42
      days). The maximum unintended pregnancy rates per cycle for temperature computers
      were estimated to be 0.0134-0.0336, for the hormonal computer 0.1155 and for mini
      microscopes 0.2313-0.2369. For the STM of NFP, there were no false infertile
      days. CONCLUSIONS: The STM of NFP proved to be the most effective contraceptive
      method to detect the fertile window among all the methods tested. The estimated
      efficacy of the other cycle monitors range from the temperature computers (upper
      level) to the hormonal computer (medium level) and the mini-microscopes with very
      low estimated contraceptive efficacy.

PMID- 14645184
TI  - Salpingectomy or proximal tubal occlusion of unilateral hydrosalpinx increases
      the potential for spontaneous pregnancy.
AB  - BACKGROUND: Studies carried out over the past 10 years have suggested that
      hydrosalpinges reduce the pregnancy rate in IVF. Here we report our observations
      of spontaneous pregnancies in patients who underwent salpingectomy (n = 18) or
      proximal tubal occlusion (n = 7) following diagnoses of unilateral hydrosalpinges
      and patent contralateral tubes. METHODS: This multi-centre, retrospective study
      included 25 infertility patients with known unilateral hydrosalpinges with a
      patent contralateral Fallopian tube. Laparoscopic treatment of unilateral
      hydrosalpinges by either salpingectomy or tubal occlusion was performed in each
      patient. Rates of subsequently observed spontaneous pregnancy, and time to
      pregnancy, are reported. RESULTS: The average duration of infertility in these
      patients was 3 years with a range of 1-10 years. Following laparoscopic surgical
      treatment, a total of 22 patients (88%) achieved intrauterine pregnancies, all
      without IVF treatment. Pregnancies occurred in an average of 5.6 months with a
      range of 1-21 months. There were no ectopic pregnancies in the study population.
      CONCLUSIONS: Selected patients with unilateral hydrosalpinges and a patent
      contralateral Fallopian tube may exhibit increased cycle fecundity after
      salpingectomy or proximal tubal occlusion of the affected tube and conceive
      without the need for IVF.

PMID- 14645185
TI  - High ratings of satisfaction with fertility treatment are common: findings from
      the Copenhagen Multi-centre Psychosocial Infertility (COMPI) Research Programme.
AB  - BACKGROUND: The aims were: (i). to identify gender differences in evaluation of
      medical and patient-centred (psychosocial) care in fertility clinics and (ii). to
      identify predictors of satisfaction. METHODS: An epidemiological prospective
      study based on questionnaire responses among all new couples attending five
      fertility clinics. The response rate at the 12 month follow-up was 87.7% and
      included a total of 1934 patients. RESULTS: During the follow-up period about two
      thirds had achieved a pregnancy and about a third became parents. The
      participants were satisfied with both the medical and patient-centred
      (psychosocial) services. There were no sex differences in the evaluation of
      treatment except that women were more satisfied than men with how the staff had
      performed their medical examinations. Satisfaction with medical and patient
      centred services was positively associated with a treatment-related
      pregnancy/delivery and the report of marital benefits resulting from the
      infertility experience. Lower social class was a significant predictor for
      satisfaction. CONCLUSIONS: Both men and women in fertility treatment had high
      ratings on medical and patient-centred care. It seemed that satisfaction with the
      psychosocial services was higher than in earlier studies from other countries.

PMID- 14645186
TI  - Results from a prospective, randomized, controlled study evaluating the
      acceptability and effects of routine pre-IVF counselling.
AB  - BACKGROUND: The aim of this study was to evaluate a model of routine pre-IVF
      counselling focusing on the narrative capacities of couples. The acceptability of
      counselling, the effects on emotional factors and the participants' assessments
      were considered. METHODS: The study included 141 consecutive childless couples
      preparing for their first IVF. Randomization was carried out through sealed
      envelopes attributing participants to counselled and non-counselled groups and
      was accepted by 100 couples. Another 12 couples refused randomization because
      they wanted counselling and 29 because they did not. Questionnaires including the
      State-Trait Anxiety Inventory, the Beck Depression Inventory and assessments of
      help were mailed to couples before IVF and counselling, and after the IVF
      outcome. RESULTS: Counselling was accepted by 79% (112/141) of couples. There was
      no significant effect of counselling on anxiety and depression scores which were
      within normal ranges at both times. Counselling provided help for 86% (75/87) of
      initially non-demanding subjects and 96% (25/26) of those initially requesting a
      session. Help was noted in areas of psychological assistance, technical
      explanations and discussing relationships. CONCLUSIONS: This model of routine
      counselling centred on the narrative provides an acceptable form of psychological
      assistance for pre-IVF couples.

PMID- 14645187
TI  - Survival of primordial follicles following prolonged transportation of ovarian
      tissue prior to cryopreservation.
AB  - BACKGROUND: Cryopreservation of ovarian tissue for fertility preservation is
      becoming increasingly common. Treatment of diseases that may deprive the ovaries
      of follicles is often performed at local hospitals that are without the necessary
      facilities and expertise to cryopreserve ovarian tissue. The aim of the present
      study was to evaluate whether primordial follicles of ovarian cortex survive
      transport for up to 4 h prior to cryopreservation. METHODS: Immediately after
      recovery of one ovary from each of four patients, the cortex was roughly
      isolated, placed in IVF culture medium, kept on ice and transported for 3-4 h to
      the centre where final dissection and cryopreservation took place.
      Transplantation of pieces of thawed ovarian cortex under the skin of
      ovariectomized immunodeficient mice for a period of 4 weeks was used to assess
      the survival of primordial follicles. RESULTS: After transplantation, ovarian
      tissue from each of the four patients contained surviving follicles. CONCLUSIONS:
      Transport of roughly isolated ovarian cortex cooled on ice for a period of up to
      4 h allows survival of primordial follicles following cryopreservation and
      transplantation to immunodeficient mice.

PMID- 14645188
TI  - Restoration of fertility in infertile mice by transplantation of cryopreserved
      male germline stem cells.
AB  - BACKGROUND: The development of a spermatogonial transplantation technique has
      provided new possibilities for the treatment of male infertility. Previous
      studies have shown that spermatogonial stem cells could reinitiate
      spermatogenesis after cryopreservation and reintroduction into the seminiferous
      tubules of infertile recipient males, and this raised the possibility of banking
      frozen stem cells for male infertility treatment. It remains unknown, however,
      whether germ cells from freeze-thawed stem cells are fertile, leaving the
      possibility that the procedure compromises the integrity of the stem cells.
      METHODS AND RESULTS: Dissociated mouse testis cells were cryopreserved and
      transplanted into infertile recipient testes. The freeze-thawed testis cell
      populations contained higher concentrations of stem cells than fresh testis cell
      populations. Offspring were obtained from freeze-thawed stem cells transplanted
      into infertile males, and fertility restoration was more efficient in immature (5
      10 days old) than in mature (6-12 weeks old) recipients. However, offspring were
      also obtained from infertile adult recipients using in-vitro microinsemination.
      CONCLUSIONS: This first successful application of frozen stem cell technology in
      the production of offspring by spermatogonial transplantation suggests the
      superiority of immature recipients for clinical applications. Thus, the
      combination of cryopreservation and transplantation of stem cells is a promising
      approach to overcome male infertility.

PMID- 14645189
TI  - Nitric oxide synthesis is increased in the endometrial tissue of women with
      endometriosis.
AB  - BACKGROUND: Previous studies have shown that peritoneal macrophages from women
      with endometriosis produce excess nitric oxide (NO). This study was designed to
      quantify the amount of NO and determine the expression of endothelial (eNOS) and
      inducible NO synthases (iNOS) in women with and without endometriosis. METHODS:
      An enzyme-linked immunosorbent assay (ELISA) was performed on endometrial tissues
      obtained from controls (myoma, n = 30) and on eutopic/ectopic endometrial tissues
      from endometriosis patients (n = 34) to evaluate eNOS and iNOS protein
      concentrations in these endometrial tissues. A rapid-response chemiluminescence
      analyser was used to measure NO directly in fresh endometrial tissues. RESULTS:
      Mean (+/- SEM) levels of NO were significantly increased in the endometrial
      tissues of women with endometriosis (13.2 +/- 7.8 versus 19.8 +/- 12.6 nmol/g
      tissue; P = 0.016). Apparently higher levels of NO were found in ectopic compared
      with eutopic endometrium (P = 0.057). Endometrial tissues of women with
      endometriosis appeared to contain more iNOS than those of controls (3.6 +/- 2.2
      versus 8.6 +/- 12.2 pg/ microg protein; P = 0.06), but no significant difference
      was found in eNOS levels. CONCLUSIONS: Greater amounts of NO and NOS are present
      in the endometrial tissues of women with endometriosis, implying a possible role
      for NO in the pathogenesis of endometriosis.

PMID- 14645191
TI  - Evidence of apoptosis in human primordial and primary follicles.
AB  - BACKGROUND: Apoptosis may operate the 'selection' between follicles destined for
      atresia and follicles that will remain available for ovulation. The aim of this
      study is to assess the expression of apoptosis in quiescent follicles. METHODS:
      Ovarian cortex samples from women of reproductive age, fixed in formalin, were
      used for immunohistochemical and terminal deoxynucleotidyl transferase-mediated
      deoxy-UTP nick end labelling (TUNEL) methods. In histological sections the
      follicles were classified as primordial, primary, secondary and antral. Follicle
      density was defined as the total number of follicles/0.5 cm(2) of ovarian
      cortical tissue. Mab DO-7 (anti-p53) and Mab 124 (anti-bcl-2) were used in the
      immunohistochemical study. RESULTS: TUNEL was positive in 23.4% of the primordial
      follicles, and in 23.2% of the primary follicles, both in oocytes and granulosa
      cells, whereas all secondary follicles were negative. Bcl-2 activity was
      expressed in 75% of secondary follicles. p53 was negative in all samples.
      CONCLUSIONS: Apoptosis could be the process responsible for atresia of quiescent
      follicles and hence depletion of the ovarian germ stockpile. Follicular cells
      expressing Bcl-2 may therefore be the viable cells that escape the apoptotic
      process. Negative p53 patterns may be a favourable prognostic finding showing
      genome integrity in the replicating follicular cells of women of reproductive
      age.

PMID- 14645190
TI  - Prolactin acts as a potent survival factor against C2-ceramide-induced apoptosis
      in human granulosa cells.
AB  - BACKGROUND: The role of prolactin in the regulation of ovarian folliculogenesis
      and corpus luteal function and in particular its relationship to atresia in these
      structures is as yet unclear. We established a model of apoptosis in which to
      examine the actions of prolactin. METHOD: Granulosa cells collected from IVF
      flush were cultured at 0.1-0.3 x 10(6) cells/well in growth media for 48 h,
      placed into serum-free media for 24 h prior to dosing for 24 h. Dose responses to
      C2-ceramide and prolactin were performed. Cells were then treated with an
      apoptotic dose of C2-ceramide alone, prolactin (100 ng/ml) alone or a combination
      of the two. Cell death was assessed by Trypan Blue cell counting and MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Thiazolyl Blue] assay and
      apoptosis confirmed by morphological assessment and flow cytometry. RESULTS: C2
      ceramide (0-40 micro mol/l) induced a dose-dependent increase in cell death
      (63.8% increase at 40 micro mol/l) and, morphologically, cells exhibited
      classical features of apoptosis. Prolactin alone had no effect on metabolic
      activity or total cell number. On co- incubation, prolactin alone had no effect
      on cell death, whereas C2-ceramide induced an approximately 62.6% increase in
      apoptosis, which was inhibited in the presence of prolactin. CONCLUSIONS:
      Prolactin may contribute significantly to early corpus luteum formation and
      survival by acting as a potent antiapoptotic factor for human granulosa cells.

PMID- 14645192
TI  - Proinsulin serum concentrations in women with polycystic ovary syndrome: a marker
      of beta-cell dysfunction?
AB  - BACKGROUND: The aim of this study was to establish the effect of polycystic ovary
      syndrome (PCOS) adjusted for adiposity on proinsulin concentrations. METHODS:
      Ninety-one women with PCOS and 72 normal cycling (NC) women were recruited. A 2
      h, 75 g oral glucose tolerance test was performed. Glucose and insulin were
      measured in each sample. Proinsulin and C-peptide were determined at 0 and 30 min
      and the fasting proinsulin/insulin ratio (PI/I) was calculated. Insulin
      sensitivity was estimated by insulin sensitivity index (ISI) composite, and beta
      cell function was estimated by insulinogenic index. RESULTS: Insulin, proinsulin
      and C-peptide concentrations were higher in women with PCOS than in NC women (P <
      0.05). PI/I and insulinogenic index were similar in both groups. Proinsulin
      concentrations increased with body mass index (P < 0.05) only in women with PCOS;
      therefore, proinsulin concentrations were higher in obese PCOS patients compared
      with obese control women (P < 0.05). Moreover, a positive association between
      proinsulin concentrations and waist diameter adjusted for C-peptide (P < 0.05)
      and a negative association between proinsulin concentrations and ISI composite
      values were observed in PCOS patients (P < 0.05). CONCLUSIONS: Data suggest that
      in PCOS patients an elevated proinsulin concentration could reflect insulin
      resistance more than beta-cell dysfunction. However, the elevated concentration
      of proinsulin in these patients could also result from impaired beta-cell
      function resulting from intra-abdominal obesity independently of insulin
      resistance.

PMID- 14645193
TI  - LH serum levels during ovarian stimulation as predictors of ovarian response and
      assisted reproduction outcome in down-regulated women stimulated with recombinant
      FSH.
AB  - BACKGROUND: There has been much debate about the effect of 'residual' LH levels
      in normogonadotrophic women undergoing assisted reproduction with GnRH agonist
      down-regulation and recombinant FSH ovarian stimulation. The aim of this
      prospective study, where receiver-operating characteristic (ROC) analysis was
      used, was to assess further the usefulness of serum LH levels as predictors of
      ovarian response, assisted reproduction treatment outcome, and the outcome of
      pregnancy when measured throughout the ovarian stimulation period in a large
      cohort of such assisted reproduction treatment women. METHODS: A total of 246
      consecutive women undergoing their first cycle of IVF or ICSI treatment were
      included in this study. Blood samples for hormone analyses were obtained on day
      S0 (the day when pituitary suppression was evidenced) and every other day from
      stimulation day 5 (S5) until the day of hCG injection. RESULTS: LH serum levels
      throughout ovarian stimulation treatment were similar for cancelled (n =32)
      versus non-cancelled (n = 214) cycles, non-conception (n = 132) versus conception
      (n = 82) cycles, and ongoing pregnancy (n = 66) versus early pregnancy loss (n =
      16) groups. There was no correlation between LH serum levels in non-cancelled
      cycles and parameters of ovarian response and assisted reproduction treatment
      outcome. ROC analysis showed that serum LH concentration during ovarian
      stimulation was unable to discriminate between cancelled and non-cancelled
      cycles, conception versus non-conception cycles, or early pregnancy loss versus
      ongoing pregnancy groups. CONCLUSIONS: Serum LH measurements during ovarian
      stimulation with recombinant FSH under pituitary suppression in
      normogonadotrophic women undergoing assisted reproduction treatment cannot
      predict ovarian response, IVF/ICSI outcome, implantation, and the outcome of
      pregnancy. Thus, there is little underlying physiological support for the
      addition of LH in stimulation protocols if daily doses of an appropriate GnRH
      agonist (leuprolide or triptorelin having lower potency than buserelin) and a
      step-down regimen of recombinant FSH administration are used.

PMID- 14645194
TI  - Luteal estradiol pre-treatment coordinates follicular growth during controlled
      ovarian hyperstimulation with GnRH antagonists.
AB  - BACKGROUND: The purpose of this study was to investigate whether luteal estradiol
      (E(2)) administration reduces follicular size discrepancies and enhances ovarian
      response in recombinant FSH (r-FSH)/GnRH antagonist protocols. METHODS: We
      studied prospectively 90 IVF-embryo transfer (ET) candidates who were randomly
      pre-treated with 17beta-E(2) (4 mg/day) from day 20 until next cycle day 2 (E(2)
      group, n = 47) or served as controls (control group, n = 43). On day 3, all women
      started r-FSH treatment. A single 3 mg dose of GnRH antagonist was administered
      eventually according to follicular maturation. Outcome measures were magnitude of
      size discrepancy of growing follicles on day 8 of r-FSH treatment and number of
      follicles >or=16 mm in diameter on the day of HCG. RESULTS: On day 8, follicles
      were smaller (9.9 +/- 2.5 versus 10.9 +/- 3.4 mm, P < 0.001) and their size
      discrepancies attenuated (P < 0.001) in the E(2) group compared with the control
      group. This was associated with more >or=16 mm follicles, mature oocytes and
      embryos in the E(2) group. CONCLUSIONS: Luteal E(2) administration reduces the
      pace of growth, improves size homogeneity of antral follicles on day 8 of r-FSH
      treatment and increases the number of follicles reaching maturation at once.
      Coordination of follicular development optimizes ovarian response to r-FSH/GnRH
      antagonist protocols and may constitute an attractive approach to improving their
      outcome.

PMID- 14645195
TI  - Does caffeine and alcohol intake before pregnancy predict the occurrence of
      spontaneous abortion?
AB  - BACKGROUND: Consumption of caffeine and alcohol is suspected to affect pregnancy
      outcome. Use of both stimulants is widespread and even minor effects on fetal
      viability are of public health interest. METHODS: We performed a nested case
      control study using prospective data from a population-based cohort comprising
      11088 women aged 20-29 years. From this cohort, women who experienced either a
      spontaneous abortion (n = 303) or who gave birth (n = 1381) during follow-up
      [mean time: 2.1 years (range: 1.6-3.4)] were selected. Associations between self
      reported exposures to caffeine and/or alcohol at enrolment and spontaneous
      abortion were analysed by means of logistic regression. RESULTS: Compared with
      women with a pre-pregnancy intake of <75 mg caffeine per day, the adjusted odds
      ratio (95% confidence interval) for spontaneous abortion was 1.26 (0.77-2.06),
      1.45 (0.87-2.41), 1.44 (0.87-2.37) and 1.72 (1.00-2.96) for a pre-pregnancy
      intake on 75-300, 301-500, 501-900 and >900 mg caffeine per day respectively (P =
      0.05 for trend). A pre-pregnancy intake of alcohol was not a predictor for
      spontaneous abortion. CONCLUSIONS: A high intake of caffeine prior to pregnancy
      seems to be associated with an increased risk of spontaneous abortion, whereas a
      low-to-moderate alcohol intake does not influence the risk.

PMID- 14645196
TI  - Self-reported difficulty in conceiving as a measure of infertility.
AB  - BACKGROUND: This study aimed to explore the meaning and potential use of women's
      self-reported difficulties in conceiving as a measure of infertility in
      epidemiological studies, and to compare women's stated reasons for infertility
      with information in their medical records. METHODS: Data were available from a
      population-based case-control study of ovarian cancer involving 1638 women. The
      sensitivity and specificity of women's self-reported infertility were calculated
      against their estimated fertility status based on detailed reproductive
      histories. Self-reported reasons for infertility were compared with diagnoses
      documented in women's medical records. RESULTS: The sensitivity of women's self
      reported difficulty in conceiving was 66 and 69% respectively when compared with
      calendar-derived and self-reported times taken trying to conceive; its
      specificity was 95%. Forty-one (23%) of the 179 women for whom medical records
      were available had their self-reported fertility problem confirmed. Self-reported
      infertility causes could be compared with diagnoses in medical records for only
      22 of these women. CONCLUSIONS: Self-reported difficulty conceiving is a useful
      measure of infertility for quantifying the burden of fertility problems
      experienced in the community. Validation of reasons for infertility is unlikely
      to be feasible through examination of medical records. Improved education of the
      public regarding the availability and success rates of infertility treatments is
      proposed.

PMID- 14645197
TI  - Clinical evidence for an LH ceiling?

PMID- 14645198
TI  - Parkin is recruited into aggresomes in a stress-specific manner: over-expression
      of parkin reduces aggresome formation but can be dissociated from parkin's effect
      on neuronal survival.
AB  - Parkinson's disease (PD) is characterized by loss of dopamine neurons in the
      substantia nigra and the presence of cytoplasmic inclusions known as Lewy bodies
      (LBs). Mutations in parkin cause autosomal recessive juvenile parkinsonism (AR
      JP) that is distinct from sporadic PD by the general absence of LBs. Several
      studies have reported that parkin is present in LBs of sporadic PD but the role
      of parkin in LB formation is unclear. Aggresomes are perinuclear aggregates
      representing intracellular deposition of misfolded protein. LBs and aggresomes
      have been reported to share a common biogenesis. We have investigated the role of
      parkin in aggresome formation. In human SH-SY5Y neuroblastoma cells we observe
      that endogenous parkin is present in aggresomes induced by a variety of stresses
      including dopamine, proteosome inhibition and a pro-apoptopic stimulus. We show
      that vimentin is invariably collapsed around the aggresome but that the detection
      of ubiquitin is variable depending on the stress. We show that cells that stably
      over-express human wild-type parkin form fewer aggresomes upon stress compared to
      cells that express vector alone whereas over-expression of AR-JP causing mutants
      of parkin have no effect on stress-induced aggresome formation. Finally, we show
      that the prevention of aggresome formation by over-expression of wild-type parkin
      is not always associated with a beneficial effect on neuronal survival. Our
      findings suggest that parkin is important for aggresome formation in human
      neuronal cells and may lead to a better understanding of the biogenesis of LBs in
      sporadic PD.

PMID- 14645199
TI  - An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome:
      interaction between genotype and epigenotype.
AB  - Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the
      deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted
      gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of
      patients have epimutations in this region. Loss of imprinting of the IGF2 gene is
      frequently observed in BWS, as is reduced CDKN1C expression related to loss of
      maternal allele-specific methylation (LOM) of the differentially methylated
      region KvDMR1. The causes of epimutations are unknown, although recently an
      association with assisted reproductive technologies has been described. To date
      the only genetic mutations described in BWS are in the CDKN1C gene. In order to
      screen for other genetic predispositions to BWS, the conserved sequences between
      human and mouse differentially methylated regions (DMRs) of the IGF2 gene were
      analyzed for variants. Four single nucleotide polymorphisms (SNPs) were found in
      DMR0 (T123C, G358A, T382G and A402G) which occurred in three out of 16 possible
      haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS
      patients and healthy controls were genotyped for the DMR0 SNPs. There was a
      significant increase in the frequency of the CAGA haplotype and a significant
      decrease in the frequency of the CATG haplotype in the patient cohort compared to
      controls. These associations were still significant in a BWS subgroup with KvDMR1
      LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated
      with LOM at KvDMR1. This indicates either a genetic predisposition to LOM or
      interactions between genotype and epigenotype that impinge on the disease
      phenotype.

PMID- 14645200
TI  - Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic
      cardiomyopathy with enhanced contractility in association with increased
      endothelial nitric oxide synthase activity.
AB  - The effect of endogenous nitric oxide synthase (NOS) on cardiac contractility and
      architecture has been a matter of debate. A role for NOS in cardiac hypertrophy
      has recently been demonstrated by studies which have shown hypertrophic
      cardiomyopathy (HCM) with altered contractility in constitutive NOS (cNOS)
      knockout mice. Caveolin-3, a strong inhibitor of all NOS isoforms, is expressed
      in sarcolemmal caveolae microdomains and binds to cNOS in vivo: endothelial
      nitric oxide synthase (eNOS) in cardiac myocytes and neuronal nitric oxide
      synthase (nNOS) in skeletal myocytes. The current study characterized the
      biochemical and cardiac parameters of P104L mutant caveolin-3 transgenic mice, a
      model of an autosomal dominant limb-girdle muscular dystrophy (LGMD1C).
      Transgenic mouse hearts demonstrated HCM, enhanced basal contractility, decreased
      left ventricular end diastolic diameter, and loss and cytoplasmic mislocalization
      of caveolin-3 protein. Surprisingly, cardiac muscle showed activation of eNOS
      catalytic activity without increased expression of all NOS isoforms. These data
      suggest that a moderate increase in eNOS activity associated with loss of
      caveolin-3 results in HCM.

PMID- 14645201
TI  - Development of an siRNA-based method for repressing specific genes in renal organ
      culture and its use to show that the Wt1 tumour suppressor is required for
      nephron differentiation.
AB  - Wt1 is a tumour suppressor gene, mutation of which is a cause of Wilms' tumour, a
      childhood renal nephroblastoma. Wt1 is expressed in a rich pattern during renal
      development suggesting that it acts at three stages: determination of the kidney
      area, the differentiation of nephrons and maturation of glomeruli. Wt1-/- mice
      confirm that Wt1 is essential for the inception of kidney development; cells that
      ought to form kidneys die by apoptosis instead. Specific human WT1 mutations
      cause defects of glomerular maturation (Denys-Drash and Frasier syndromes),
      providing circumstantial evidence for action of Wt1 during glomerular maturation.
      There is, however, no genetic evidence for a function during nephron
      differentiation because this stage is never reached in Wt1-/- mice. We have
      therefore developed a novel technique, based on small interfering RNA (siRNA), to
      repress the expression of Wt1 and other specific genes at different stages of
      kidney development in culture. We find that early repression of Wt1 phenocopies
      the Wt1-/- mouse, but later repression prevents cells differentiating into
      nephrons and causes them instead to proliferate abnormally, possibly mimicking
      aspects of Wilms' tumour. In line with established hypotheses about genetic
      pathways that control kidney development, we find that repressing Pax2 using
      siRNAs represses Wt1 expression and blocks both bud growth and nephron
      differentiation, but that repressing Wnt4 blocks nephron differentiation without
      affecting Wt1 expression. As well as illuminating previously inaccessible aspects
      of Wt1 biology, our results suggest that siRNA in organ culture will be a
      powerful method for analyzing other developmental pathways and testing the
      effects of stage-specific loss of tumour suppressor genes.

PMID- 14645202
TI  - Replication timing of the human genome.
AB  - We have developed a directly quantitative method utilizing genomic clone DNA
      microarrays to assess the replication timing of sequences during the S phase of
      the cell cycle. The genomic resolution of the replication timing measurements is
      limited only by the genomic clone size and density. We demonstrate the power of
      this approach by constructing a genome-wide map of replication timing in human
      lymphoblastoid cells using an array with clones spaced at 1 Mb intervals and a
      high-resolution replication timing map of 22q with an array utilizing overlapping
      sequencing tile path clones. We show a positive correlation, both genome-wide and
      at a high resolution, between replication timing and a range of genome parameters
      including GC content, gene density and transcriptional activity.

PMID- 14645203
TI  - Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of
      oculopharyngeal muscular dystrophy.
AB  - Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is a late-onset
      disorder characterized clinically by progressive ptosis, dysphagia and limb
      weakness, and by unique intranuclear inclusions in the skeletal muscle fibers.
      The disease is caused by the expansion of a 10-alanine stretch to 12-17 alanine
      residues in the poly(A)-binding protein, nuclear 1 (PABPN1; PABP2). While PABPN1
      is a major component of the inclusions in OPMD, the exact cause of the disease is
      unknown. To elucidate the molecular mechanism and to construct a useful model for
      therapeutic trials, we have generated transgenic mice expressing the hPABPN1.
      Transgenic mice lines expressing a normal hPABPN1 with 10-alanine stretch did not
      reveal myopathic changes, whereas lines expressing high levels of expanded
      hPABPN1 with a 13-alanine stretch showed an apparent myopathy phenotype,
      especially in old age. Pathological studies in the latter mice disclosed
      intranuclear inclusions consisting of aggregated mutant hPABPN1 product.
      Furthermore, some TUNEL positive nuclei were shown around degenerating fibers and
      a cluster of it in the lesion in necrotic muscle fibers. Interestingly, the
      degree of myopathic changes was more prominent in the eyelid and pharyngeal
      muscles. Further, muscle weakness in the limbs was apparent as shown by the
      fatigability test. Nuclear inclusions seemed to develop gradually with aging, at
      least after 1 week of age, in model mouse muscles. We established the first
      transgenic mouse model of OPMD by expressing mutated PABPN1, and our model mice
      appear to have more dramatic alternations in myofiber viability.

PMID- 14645204
TI  - Characterization of ARC, apoptosis repressor interacting with CARD, in normal and
      dystrophin-deficient skeletal muscle.
AB  - Duchenne muscular dystrophy is an X-linked recessive disorder, primarily
      characterized by progressive muscle weakness and wasting. The disease results
      from the absence of dystrophin, however the precise molecular mechanisms leading
      to muscle pathology are poorly understood. Dystrophic muscles undergo increased
      oxidative stress and altered calcium homeostasis, which may contribute to
      myofiber loss by triggering both necrosis and apoptosis. Recent studies have
      identified ARC (apoptosis repressor with caspase recruitment domain) as an
      abundant protein in human muscle that can inhibit both hypoxia and caspase-8
      induced apoptosis as well as protect cells from oxidative stress. To explore a
      potential role for ARC in protecting muscle fibers from dystrophic breakdown, we
      have cloned and characterized murine ARC and studied its expression in normal and
      dystrophic mouse muscle. ARC is expressed at high levels in striated muscle and
      displays fiber-type restricted expression patterns. ARC expression levels are
      normal in dystrophic mdx mice, although the intracellular localization pattern of
      ARC is slightly altered compared with normal muscles. Overexpression of ARC in
      transgenic mdx mice failed to alleviate the dystrophic pathology in skeletal
      muscles, suggesting that misregulation of the molecular pathways regulated by ARC
      does not significantly contribute to myofiber death.

PMID- 14645205
TI  - Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid
      peptide in vivo: evidence for augmentation of a 42-specific gamma secretase.
AB  - Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and
      gamma-secretase to release amyloid peptides (Abeta40 and 42) that aggregate to
      form senile plaques in the brains of patients with Alzheimer's disease (AD). The
      C-terminus of Abeta40/42 is generated by gamma-secretase, whose activity is
      dependent upon presenilin (PS 1 or 2). Missense mutations in PS1 (and PS2) occur
      in patients with early-onset familial AD (FAD), and previous studies in
      transgenic mice and cultured cell models demonstrated that FAD-PS1 variants shift
      the ratio of Abeta40 : 42 to favor Abeta42. One hypothesis to explain this
      outcome is that mutant PS alters the specificity of gamma-secretase to favor
      production of Abeta42 at the expense of Abeta40. To test this hypothesis in vivo,
      we studied Abeta40 and 42 levels in a series of transgenic mice that co-express
      the Swedish mutation of APP (APPswe) with two FAD-PS1 variants that
      differentially accelerate amyloid pathology in the brain. We demonstrate a direct
      correlation between the concentration of Abeta42 and the rate of amyloid
      deposition. We further show that the shift in Abeta42 : 40 ratios associated with
      the expression of FAD-PS1 variants is due to a specific elevation in the steady
      state levels of Abeta42, while maintaining a constant level of Abeta40. These
      data suggest that PS1 variants do not simply alter the preferred cleavage site
      for gamma-secretase, but rather that they have more complex effects on the
      regulation of gamma-secretase and its access to substrates.

PMID- 14645207
TI  - A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous
      recombination at DNA replication forks.
AB  - Homologous recombination repair (HRR) is required for both the repair of DNA
      double strand breaks (DSBs) and the maintenance of the integrity of DNA
      replication forks. To determine the effect of a mutant allele of the RAD51
      paralog XRCC2 (342delT) found in an HRR-defective tumour cell line, 342delT was
      introduced into HRR proficient cells containing a recombination reporter
      substrate. In one set of transfectants, expression of 342delT conferred
      sensitivity to thymidine and mitomycin C and suppressed HRR induced at the
      recombination reporter by thymidine but not by DSBs. In a second set of
      transfectants, the expression of 342delT was accompanied by a decreased level of
      the full-length XRCC2. These cells were defective in the induction of HRR by
      either thymidine or DSBs. Thus 342delT suppresses recombination induced by
      thymidine in a dominant negative manner while recombination induced by DSBs
      appears to depend upon the level of XRCC2 as well as the expression of the mutant
      XRCC2 allele. These results suggest that HRR pathways responding to stalled
      replication forks or DSBs are genetically distinguishable. They further suggest a
      critical role for XRCC2 in HRR at replication forks, possibly in the loading of
      RAD51 onto gapped DNA.

PMID- 14645206
TI  - Polymorphism at the C-reactive protein locus influences gene expression and
      predisposes to systemic lupus erythematosus.
AB  - Relative deficiency of pentraxin proteins is implicated in the pathogenesis of
      systemic lupus erythematosus. The C-reactive protein (CRP) response is defective
      in patients with acute flares of disease, and mice with targeted deletions of the
      serum amyloid P component gene (Sap) develop a lupus-like illness. In humans, the
      genes for CRP (CRP) and SAP (APCS) map to 1q23.2 within an interval linked with
      SLE. We have investigated the candidate genes CRP and APCS in two cohorts
      totalling 586 UK simplex SLE families. The inheritance of an intronic
      dinucleotide repeat and seven single nucleotide polymorphisms in the CRP and APCS
      genes was examined by application of family-based tests of association and
      linkage. Basal levels of CRP were influenced independently by two polymorphisms
      at the CRP locus, CRP 2 and CRP 4. Furthermore, the latter polymorphism was
      linked/associated with SLE and antinuclear autoantibody production. Thus, the
      polymorphism associated with reduced basal CRP was also associated with the
      development of SLE. These data support the hypothesis that defective disposal of
      potentially immunogenic material is a contributory factor in lupus pathogenesis.
      The identification of polymorphisms that determine basal CRP levels has
      implications in ischaemic heart disease, where CRP level is an important
      predictor of risk.

PMID- 14645208
TI  - Cellular genomic reporter assays for screening and evaluation of inducers of
      fetal hemoglobin.
AB  - Reactivation of fetal hemoglobin (HbF) expression using pharmacological agents
      represents a potential strategy for the therapy of beta-thalassemia, sickle cell
      disease, HbE and other beta-hemoglobinopathies. However, the drugs currently
      available have low efficacy and specificity and are associated with high
      toxicity. We describe the development of stable cellular genomic reporter assays
      (GRAs) based on the green fluorescence protein (EGFP) gene under the Ggamma
      globin promoter in the intact human beta-globin locus. We show that human
      erythroleukemic cell lines stably transfected with a Ggamma-EGFP beta-globin
      locus construct can maintain a uniform basal level of EGFP expression over long
      periods of continuous culture and that induction of EGFP expression parallels the
      induction of the endogenous globin genes. We compared the EGFP-induction potency
      of a number of chemotherapeutic agents, including histone deacetylase inhibitors
      and DNA-binding agents. We show that hydroxyurea and butyrate result in moderate
      levels of induction (70-80%) but with an additive inductive effect. Among the DNA
      binding agents tested, cisplatin was the most potent inducer of HbF expression,
      (442+/-32%), a level which is comparable to hemin (764+/-145%). These results
      indicate that cellular GRAs containing Ggamma-EGFP-modified beta-globin locus
      constructs can be used to develop novel inducers of HbF synthesis for the therapy
      of beta-hemoglobinopathies.

PMID- 14645209
TI  - Muscle: a nontraditional 1,25-dihydroxyvitamin D target tissue exhibiting classic
      hormone-dependent vitamin D receptor actions.

PMID- 14645210
TI  - Glucagon-like peptide-1 and the islet beta-cell: augmentation of cell
      proliferation and inhibition of apoptosis.

PMID- 14645211
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14645212
TI  - National Hormone and Peptide Program. National Institute of Diabetes and
      Digestive and Kidney Diseases. Peptide hormones, antisera other reagents
      available.

PMID- 14645213
TI  - Unconventional secretion of fibroblast growth factor 2 is mediated by direct
      translocation across the plasma membrane of mammalian cells.
AB  - Fibroblast growth factor 2 (FGF-2) is a pro-angiogenic mediator that is secreted
      by both normal and neoplastic cells. Intriguingly, FGF-2 has been shown to be
      exported by an endoplasmic reticulum/Golgi-independent pathway; however, the
      molecular machinery mediating this process has remained elusive. Here we
      introduce a novel in vitro system that functionally reconstitutes FGF-2
      secretion. Based on affinity-purified plasma membrane inside-out vesicles, we
      demonstrate post-translational membrane translocation of FGF-2 as shown by
      protease protection experiments. This process is blocked at low temperature but
      apparently does not appear to be driven by ATP hydrolysis. FGF-2 membrane
      translocation occurs in a unidirectional fashion requiring both integral and
      peripheral membrane proteins. These findings provide direct evidence that FGF-2
      secretion is based on its direct translocation across the plasma membrane of
      mammalian cells. When galectin-1 and macrophage migration inhibitory factor,
      other proteins exported by unconventional means, were analyzed for translocation
      into plasma membrane inside-out vesicles, galectin-1 was found to be transported
      as efficiently as FGF-2. By contrast, migration inhibitory factor failed to
      traverse the membrane of inside-out vesicles. These findings establish the
      existence of multiple distinct secretory routes that are operational in the
      absence of a functional endoplasmic reticulum/Golgi system.

PMID- 14645214
TI  - Identification of Murr1 as a regulator of the human delta epithelial sodium
      channel.
AB  - The human delta epithelial sodium channel (deltaENaC) subunit is related to the
      alpha-, beta-, and gammaENaC subunits that control salt homeostasis. DeltaENaC
      forms an amiloride-sensitive Na+ channel with the beta and gamma subunits.
      However, the in vivo function of deltaENaC is not known. To gain insight into the
      function of deltaENaC, a yeast two-hybrid screen of a human brain cDNA library
      was carried out using the C- and N-terminal domains of deltaENaC. A novel
      deltaENaC-interacting protein called Murr1 (mouse U2af1-rs1 region) was isolated
      in the C-terminal domain screen. Murr1 is a 21-kDa protein mutated in Bedlington
      terriers suffering from copper toxicosis. The interaction of Murr1 and deltaENaC
      was confirmed by glutathione S-transferase pulldown assay and
      coimmunoprecipitation. To test the functional significance of the interaction,
      Murr1 was coexpressed with deltabetagammaENaC in Xenopus oocytes. Murr1 inhibited
      amiloride-sensitive sodium current in a dose-dependent manner. In addition,
      deletion of the last 59 amino acids of deltaENaC abolished the inhibition. Murr1
      also bound to the beta- and gammaENaC subunits and inhibited alphabetagammaENaC
      sodium current. Therefore, these results suggest that Murr1 is a novel regulator
      of ENaC.

PMID- 14645215
TI  - Molecular mechanisms of Cl- transport by the renal Na(+)-K(+)-Cl- cotransporter.
      Identification of an intracellular locus that may form part of a high affinity
      Cl(-)-binding site.
AB  - The 2nd transmembrane domain (tm) of the secretory Na(+)-K(+)-Cl(-) cotransporter
      (NKCC1) and of the kidney-specific isoform (NKCC2) has been shown to play an
      important role in cation transport. For NKCC2, by way of illustration,
      alternative splicing of exon 4, a 96-bp sequence from which tm2 is derived, leads
      to the formation of the NKCC2A and F variants that both exhibit unique affinities
      for cations. Of interest, the NKCC2 variants also exhibit substantial differences
      in Cl- affinity as well as in the residue composition of the first intracellular
      connecting segment (cs1a), which immediately follows tm2 and which too is derived
      from exon 4. In this study, we have prepared chimeras of the shark NKCC2A and F
      (saA and saF) to determine whether cs1a could play a role in Cl- transport; here,
      tm2 or cs1a in saF was replaced by the corresponding domain from saA (generating
      saA/F or saF/A, respectively). Functional analyses of these chimeras have shown
      that cs1a-specific residues account for most of the A-F difference in Cl-
      affinity. For example, Km(Cl-)s were approximately 8 mm for saF/A and saA, and
      approximately 70 mm for saA/F and saF. Intriguingly, variant residues in cs1a
      also affected cation transport; here, Km(Na+)s for the chimeras and for saA were
      all approximately 20 mM, and Km(Rb+) all approximately 2 mM. Regarding tm2, our
      studies have confirmed its importance in cation transport and have also
      identified novel properties for this domain. Taken together, our results
      demonstrate for the first time that an intracellular loop in NKCC contributes to
      the transport process perhaps by forming a flexible structure that positions
      itself between membrane spanning domains.

PMID- 14645216
TI  - Residues in the distal heme pocket of neuroglobin. Implications for the multiple
      ligand binding steps.
AB  - Amino acid residues in the ligand binding pocket of human neuroglobin have been
      identified by site-directed mutagenesis and their properties investigated by
      resonance Raman and flash photolysis methods. Wild-type neuroglobin has been
      shown to have six-coordinate heme in both ferric and ferrous states. Substitution
      of His96 by alanine leads to complete loss of heme, indicating that His96 is the
      proximal ligand. The resonance Raman spectra of M69L and K67T mutants were
      similar to those of wild-type (WT) neuroglobin in both ferric and ferrous states.
      By contrast, H64V was six-coordinate high-spin and five-coordinate high-spin in
      the ferric and ferrous states, respectively, at acidic pH. The spectra were pH
      dependent and six-coordinate with the low-spin component dominating at alkaline
      pH. In a double mutant H64V/K67T, the high-spin component alone was detected in
      the both ferric and the ferrous states. This implies that His64 is the endogenous
      ligand and that Lys67 is situated nearby in the distal pocket. In the ferrous
      H64V and H64V/K67T mutants, the nu(Fe-His) stretching frequency appears at 221
      cm(-1), which is similar to that of deoxymyoglobin. In the ferrous CO-bound
      state, the nu(Fe-CO) stretching frequency was detected at 521 and 494 cm(-1) in
      WT, M69L, and K67T, while only the 494 cm(-1) component was detected in the H64V
      and H64V/K67T mutants. Thus, the 521 cm(-1) component is attributed to the
      presence of polar His64. The CO binding kinetics were biphasic for WT, H64V, and
      K67T and monophasic for H64V/K67T. Thus, His64 and Lys67 comprise a unique distal
      heme pocket in neuroglobin.

PMID- 14645217
TI  - Crystal structure of an invertebrate caspase.
AB  - Caspases play an essential role in the execution of apoptosis. These cysteine
      proteases are highly conserved among metazoans and are translated as inactive
      zymogens, which are activated by proteolytic cleavages to generate the large and
      small subunits and remove the N-terminal prodomain. The 2.3 A resolution crystal
      structure of active Sf-caspase-1, the principal effector caspase of the insect
      Spodoptera frugiperda, is presented here. The structure represents the first
      nonhuman caspase to be resolved. The structure of the cleaved and active protease
      was determined with the tetrapeptide inhibitor N-acetyl-Asp-Glu-Val-Asp
      chloromethylketone covalently bonded to the active site cysteine. As expected,
      the overall fold of Sf-caspase-1 is exceedingly similar to that of the five
      active caspases from humans solved to date. The overall structure and active site
      arrangement of Sf-caspase-1 is most comparable with that of the human effector
      caspases, with which it shares highest sequence homology. The most prominent
      structural difference with Sf-caspase-1 is the position of the N-terminal region
      of the large subunit. Unlike the N terminus of human caspases, the N terminus of
      Sf-caspase-1 originates from the active site side where it interacts with active
      site loop L2 and then extends to the backside of the heterodimer. This unusual
      structural arrangement raises the possibility that the N-terminal prodomain plays
      a regulatory role during effector caspase activation or enzyme activity in
      insects.

PMID- 14645218
TI  - Casein kinase II-mediated phosphorylation regulates alpha-synuclein/synphilin-1
      interaction and inclusion body formation.
AB  - Alpha-synuclein is a phosphoprotein that accumulates as a major component of Lewy
      bodies in the brains of patients with Parkinson disease. Synphilin-1, which is
      also present in Lewy bodies, binds with alpha-synuclein and forms cytoplasmic
      inclusions in transfected cells. Yet the molecular determinants of this protein
      protein interaction are unknown. Here we report that casein kinase II (CKII)
      phosphorylates synphilin-1 and that the beta subunit of this enzyme complex binds
      to synphilin-1. Additionally, both CKII alpha and beta subunits are present
      within cytoplasmic inclusions in cells that overexpress synphilin-1. Notably, the
      interaction between synphilin-1 and alpha-synuclein is markedly dependent on
      phosphorylation. Inhibition of CKII activity by 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole blocks the binding between these two proteins and
      significantly reduces the percentage of cells that contain eosinophilic
      cytoplasmic inclusions. Mutation of the major CKII phosphorylation site in alpha
      synuclein (S129A) has no significant impact on the binding between alpha
      synuclein and synphilin-1 or on the formation of synphilin-1/alpha-synuclein
      positive inclusions. These data suggest that the CKII-mediated phosphorylation of
      synphilin-1 rather than that of alpha-synuclein is critical in modulating their
      tendency to aggregate into inclusions. These observations collectively indicate
      that a ubiquitous post-translational modification such as phosphorylation can
      regulate inclusion body formation in the context of alpha-synuclein and synphilin
      1 interaction.

PMID- 14645219
TI  - Phosphoinositide 3-kinase-mediated activation of cofilin phosphatase Slingshot
      and its role for insulin-induced membrane protrusion.
AB  - Cofilin plays an essential role in actin filament dynamics and membrane
      protrusion in motile cells. Cofilin is inactivated by phosphorylation at Ser-3 by
      LIM kinase and reactivated by dephosphorylation by cofilin-phosphatase Slingshot
      (SSH). Although cofilin is dephosphorylated in response to various extracellular
      stimuli, signaling pathways regulating SSH activation and cofilin
      dephosphorylation have remained to be elucidated. Here we show that insulin
      stimulates the phosphatase activity of Slingshot-1L (SSH1L) and cofilin
      dephosphorylation in cultured cells, in a manner dependent on phosphoinositide 3
      kinase (PI3K) activity. Consistent with this, the level of Ser-3-phosphorylated
      cofilin is increased in PTEN (phosphatase and tensin homolog deleted in
      chromosome 10)-overexpressing cells and decreased in PTEN-deficient cells.
      Insulin induced the accumulation of SSH1L and active Akt (a downstream effector
      of PI3K), together with a PI3K product phosphatidylinositol 3,4,5-trisphosphate,
      onto membrane protrusions. Cofilin, but not Ser-3-phosphorylated cofilin,
      accumulated in membrane protrusions in insulin-stimulated cells, indicating that
      cofilin is dephosphorylated in these areas. Finally, suppression of SSH1L
      expression by RNA interference abolished insulin-induced cofilin
      dephosphorylation and the membrane protrusion. These findings suggest that SSH1L
      is activated downstream of PI3K and plays a critical role in insulin-induced
      membrane protrusion by dephosphorylating and activating cofilin.

PMID- 14645220
TI  - Relative contribution of Nedd4 and Nedd4-2 to ENaC regulation in epithelia
      determined by RNA interference.
AB  - Epithelial Na+ transport is regulated in large part by mechanisms that control
      expression of the epithelial Na+ channel (ENaC) at the cell surface. Nedd4 and
      Nedd4-2 are candidates to control ENaC surface expression, but it is not known
      which of these proteins contributes to ENaC regulation in epithelia. To address
      this question, we used RNA interference to selectively reduce expression of Nedd4
      or Nedd4-2. We found that endogenous Nedd4-2, but not Nedd4, negatively regulates
      ENaC in two epithelial cell lines (Fischer rat thyroid and H441); small
      interfering RNA (siRNA) against Nedd4-2 increased amiloride-sensitive Na+ current
      (compared with control siRNA), but Nedd4 siRNA did not. A mutation associated
      with Liddle's syndrome (betaR566X) abolished the effect of Nedd4-2 siRNA,
      suggesting that a defect in ENaC regulation by Nedd4-2 contributes to the
      pathogenesis of this inherited form of hypertension. Previous work found that
      Nedd4-2 is phosphorylated by serum and glucocorticoid-regulated kinase, a Ser/Thr
      kinase induced by steroid hormones. Here we found that Nedd4-2 phosphorylation
      contributes to ENaC regulation by steroid hormones. Consistent with this model,
      ENaC stimulation by dexamethasone was reduced by Nedd4-2 siRNA and by
      overexpression of a mutant Nedd4-2 lacking serum and glucocorticoid-regulated
      kinase phosphorylation sites. Thus, endogenous Nedd4-2 negatively regulates ENaC
      in epithelia and is a component of a signaling pathway by which steroid hormones
      regulate ENaC. Defects in this regulation may contribute to the pathogenesis of
      hypertension.

PMID- 14645221
TI  - Histone acetyltransferase-dependent chromatin remodeling and the vascular clock.
AB  - Rhythmic gene expression is central to the circadian control of physiology in
      mammals. Transcriptional activation of Per and Cry genes by heterodimeric bHLH
      PAS proteins is a key event in the feedback loop that drives rhythmicity;
      however, the mechanism is not clearly understood. Here we show the
      transcriptional coactivators and histone acetyltransferases, p300/CBP, PCAF, and
      ACTR associate with the bHLH-PAS proteins, CLOCK and NPAS2, to regulate
      positively clock gene expression. Furthermore, Cry2 mediated repression of
      NPAS2:BMAL1 is overcome by overexpression of p300 in transactivation assays.
      Accordingly, p300 exhibits a circadian time-dependent association with NPAS2 in
      the vasculature, which precedes peak expression of target genes. In addition, a
      rhythm in core histone H3 acetylation on the mPer1 promoter in vivo correlates
      with the cyclical expression of their mRNAs. Temporal coactivator recruitment and
      HAT-dependent chromatin remodeling on the promoter of clock controlled genes in
      the vasculature permits the mammalian clock to orchestrate circadian gene
      expression.

PMID- 14645222
TI  - Decrease of H2O2 plasma membrane permeability during adaptation to H2O2 in
      Saccharomyces cerevisiae.
AB  - Contrary to what is widely believed, recent published results show that H2O2 does
      not freely diffuse across biomembranes. The fast removal of H2O2 by antioxidant
      enzymes is able to generate a gradient if H2O2 is produced in a different
      compartment from that containing the enzymes (Antunes, F., and Cadenas, E. (2000)
      FEBS Lett. 475, 121-126). In this work, we extended these studies and tested
      whether an active regulation of biomembranes permeability characteristics is part
      of the cell response to oxidative stress. Using Saccharomyces cerevisiae as a
      model, we showed that: (a) H2O2 gradients across the plasma membrane are formed
      upon exposure to external H2O2; (b) there is a correlation between the magnitude
      of the gradients and the resistance to H2O2; (c) there is not a correlation
      between the intracellular capacity to remove H2O2 and the resistance to H2O2; (d)
      the plasma membrane permeability to H2O2 decreases by a factor of two upon
      acquisition of resistance to this agent by pre-exposing cells either to nonlethal
      doses of H2O2 or to cycloheximide, an inhibitor of protein synthesis; and (e)
      erg3Delta and erg6Delta mutants, which have impaired ergosterol biosynthesis
      pathways, show higher plasma membrane permeability to H2O2 and are more sensitive
      to H2O2. Altogether, the regulation of the plasma membrane permeability to H2O2
      emerged as a new mechanism by which cells respond and adapt to H2O2. The
      consequences of the results to cellular redox compartmentalization and to the
      origin and evolution of the eukaryotic cell are discussed.

PMID- 14645223
TI  - The crystal structures of the ferric and ferrous forms of the heme complex of
      HmuO, a heme oxygenase of Corynebacterium diphtheriae.
AB  - Crystal structures of the ferric and ferrous heme complexes of HmuO, a 24-kDa
      heme oxygenase of Corynebacterium diphtheriae, have been refined to 1.4 and 1.5 A
      resolution, respectively. The HmuO structures show that the heme group is closely
      sandwiched between the proximal and distal helices. The imidazole group of His-20
      is the proximal heme ligand, which closely eclipses the beta- and delta-meso axis
      of the porphyrin ring. A long range hydrogen bonding network is present,
      connecting the iron-bound water ligand to the solvent water molecule. This
      enables proton transfer from the solvent to the catalytic site, where the oxygen
      activation occurs. In comparison to the ferric complex, the proximal and distal
      helices move closer to the heme plane in the ferrous complex. Together with the
      kinked distal helix, this movement leaves only the alpha-meso carbon atom
      accessible to the iron-bound dioxygen. The heme pocket architecture is
      responsible for stabilization of the ferric hydroperoxo-active intermediate by
      preventing premature heterolytic O-O bond cleavage. This allows the enzyme to
      oxygenate selectively at the alpha-meso carbon in HmuO catalysis.

PMID- 14645224
TI  - Evidence that C promoter-binding factor 1 binding is required for Notch-1
      mediated repression of activator protein-1.
AB  - Cell fate determination in invertebrate and vertebrate systems is regulated by
      the Notch signaling pathway. Four mammalian Notch genes, Notch 1-4, encode
      differentially expressed transmembrane receptors. The canonical Notch pathway
      involves proteolytic liberation of the Notch-1 intracellular domain (NIC-1),
      which activates CSL (CBF1, Su(H), and Lag-1)-mediated transactivation. We showed
      previously that NIC-1 also represses activator protein-1 (AP-1)-mediated
      transactivation. The N-terminal RAM (RBP-Jkappa associated molecule) domain of
      NIC-1 was required for both activation and repression. To investigate the
      mechanism of AP-1 repression, we tested whether distinct sequences within the RAM
      domain mediate activation versus repression. We analyzed the capacity of RAM
      domain mutants to bind endogenous CBF1, to activate CSL-mediated transactivation,
      and to repress AP-1. A mutant lacking 20 amino acids of the RAM domain (Delta1759
      1778) resembled the RAM domain deletion mutant in being defective in all
      activities. Analysis of 14 deletion and alanine substitution mutants revealed a
      correlation between CBF1 binding, CSL-mediated transactivation, and AP-1
      repression. Stably transfected K562 cells could only tolerate very low level
      expression of wild-type NIC-1 and NIC-1 mutants retaining activation/repression
      activities. By contrast, transcriptionally compromised NIC-1 mutants accumulated
      at high levels. These results support a model in which the binding of NIC-1 to
      CBF1 is required for AP-1 repression and reveal a powerful cell-sensing mechanism
      that suppresses the levels of transcriptionally competent NIC-1.

PMID- 14645225
TI  - The human amyloid-beta precursor protein770 mutation V717F generates peptides
      longer than amyloid-beta-(40-42) and flocculent amyloid aggregates.
AB  - One of the familial forms of Alzheimer's disease (AD) encodes the amyloid-beta
      precursor protein (AbetaPP) substitution mutation V717F. This mutation is
      relevant to AD research, since it has been utilized to generate transgenic mice
      models to study AD pathology and therapeutic interventions. Amyloid beta (Abeta)
      peptides were obtained from the cerebral tissue of three familial AD subjects
      carrying the AbetaPP V717F mutation. A combination of ultracentrifugation, size
      exclusion, and reverse-phase high performance liquid chromatography, tryptic and
      cyanogen bromide hydrolysis, amino acid analysis, and matrix-assisted laser
      desorption ionization and surface-enhanced laser desorption ionization mass
      spectrometry was used to characterize the familial AD mutant Abeta peptides. The
      AbetaPP V717F mutation, located 4-6 residues beyond the wild-type AbetaPP gamma
      secretase cleavage site, yielded longer Abeta peptides with C termini between
      residues 43 and 54. In the cerebral cortex these peptides aggregated into thin
      water- and SDS-insoluble amyloid bundles that condensed into flocculent spherical
      plaques. In the leptomeningeal arteries the amyloid was deposited in moderate
      amounts and was primarily composed of the shorter and more soluble Abeta species
      ending at residues 40, 42, and 44. The single V717F mutation in AbetaPP results
      in distinctive and drastic changes in the length and tertiary structure of Abeta
      peptides, which appear to be responsible for the earlier clinical manifestations
      of dementia and death of these patients.

PMID- 14645226
TI  - Effect of N-terminal and Met23 mutations on the structure and dynamics of
      onconase.
AB  - Onconase (rONC), otherwise known as ranpirnase or P-30 protein, which was
      initially purified from extracts of Rana pipiens oocytes and early embryos,
      exhibits anticancer activity both in vitro and in vivo and is in phase III
      clinical trials for tumor therapy. We have determined the solution NMR structure
      of a recombinant onconase with Met(-1), Gln1, and Leu23 residues (M-1, Q1,
      M23L)rONC. The 20 best solution structures had a backbone root mean square
      deviation of 0.41 +/- 0.09 A with respect to the average structure. The energy
      minimized average NMR structure had a backbone root mean square deviation of 0.72
      A from the x-ray crystallographic structure of native onconase; however, the
      orientation of the N-terminal residue in the two structures was very different.
      Comparison of the 15N HSQC spectrum of (M-1, Q1, M23L)rONC with that of a mutant
      E1S-rONC, which is identical to the nONC except with the N-terminal pyroglutamyl
      residue replaced by Ser, showed that N-terminal and residue 23 mutations induced
      structural changes in regions beyond the mutation sites. Model-free analysis of
      the backbone amide 15N-T1, 15N-T2, and 15N-1H NOE relaxation data for (M-1, Q1,
      M23L)rONC and E1S-rONC revealed that the E1S-rONC molecule showed very little
      flexibility, whereas (M-1, Q1, M23L)rONC exhibited substantial flexibility, which
      may account for the previously observed reduced stability and increased protease
      susceptibility. The alpha1 helix and beta-sheets of (M-1, Q1, M23L)rONC displayed
      bending motions. These data provided strong evidence for the presence of an N
      terminal hydrogen bond network in E1S-rONC, but not in (M-1, Q1, M23L)rONC.

PMID- 14645227
TI  - Regulation of immunoglobulin promoter activity by TFII-I class transcription
      factors.
AB  - The restriction of immunoglobulin variable region promoter activity to B
      lymphocytes is a well known paradigm of promoter specificity. Recently, a cis
      element, located downstream of the transcription initiation site of murine heavy
      chain variable promoters, was shown to be critical for B cell activity and
      specificity. Here we show that mutation of this element, termed DICE (Downstream
      Immunoglobulin Control Element), reduces in vivo activity in B cells. Gel
      mobility shift assays show that DICE forms B cell-specific complexes that were
      also sensitive to DICE mutation. DICE mutation strongly reduces the ability of a
      distal immunoglobulin heavy chain intronic enhancer to stimulate transcription.
      We also identify a DICE-interacting factor: a TFII-I-related protein known as BEN
      (also termed Mus-TRD1 and WBSCR11). Dominant-negative and RNAi-mediated knockdown
      experiments indicate that BEN can both positively and negatively regulate IgH
      promoter activity, depending on the cell line.

PMID- 14645228
TI  - Cytochrome c551 from Starkeya novella: characterization, spectroscopic
      properties, and phylogeny of a diheme protein of the SoxAX family.
AB  - Cytochromes from the SoxAX family have a major role in thiosulfate oxidation via
      the thiosulfate-oxidizing multi-enzyme system (TOMES). Previously characterized
      SoxAX proteins from Rhodovulum sulfidophilum and Paracoccus pantotrophus contain
      three heme c groups, two of which are located on the SoxA subunit. In contrast,
      the SoxAX protein purified from Starkeya novella was found to contain only two
      heme groups. Mass spectrometry showed that a disulfide bond replaced the second
      heme group found in the diheme SoxA subunits. Apparent molecular masses of 27,229
      +/- 10.3 Da and 20,258.6 +/- 1 Da were determined for SoxA and SoxX with an
      overall mass of 49.7 kDa, indicating a heterodimeric structure. Optical redox
      potentiometry found that the two heme cofactors are reduced at similar potentials
      (versus NHE) that are as follows: +133 mV (pH 6.0); +104 mV (pH 7.0); +49 (pH
      7.9) and +10 mV (pH 8.7). EPR spectroscopy revealed that both ferric heme groups
      are in the low spin state, and the spectra were consistent with one heme having a
      His/Cys axial ligation and the other having a His/Met axial ligation. The His/Cys
      ligated heme is present in different conformational states and gives rise to
      three distinct signals. Amino acid sequencing was used to unambiguously assign
      the protein to the encoding genes, soxAX, which are part of a complete sox gene
      cluster found in S. novella. Phylogenetic analysis of soxA- and soxX-related gene
      sequences indicates a parallel development of SoxA and SoxX, with the diheme and
      monoheme SoxA sequences located on clearly separated branches of a phylogenetic
      tree.

PMID- 14645229
TI  - Regulation of collagenase activities of human cathepsins by glycosaminoglycans.
AB  - Cathepsin K, a lysosomal papain-like cysteine protease, forms collagenolytically
      highly active complexes with chondroitin sulfate and represents the most potent
      mammalian collagenase. Here we demonstrate that complex formation with
      glycosaminoglycans (GAGs) is unique for cathepsin K among human papain-like
      cysteine proteases and that different GAGs compete for the binding to cathepsin
      K. GAGs predominantly expressed in bone and cartilage, such as chondroitin and
      keratan sulfates, enhance the collagenolytic activity of cathepsin K, whereas
      dermatan, heparan sulfate, and heparin selectively inhibit this activity.
      Moreover, GAGs potently inhibit the collagenase activity of other cysteine
      proteases such as cathepsins L and S at 37 degrees C. Along this line MMP1
      generated collagen fragments in the presence of GAGs are stable against further
      degradation at 28 degrees C by all cathepsins but cathepsin K, whereas thermal
      destabilization at 37 degrees C renders the fragments accessible to all
      cathepsins. These results suggest a novel mechanism for the regulation of matrix
      protein degradation by GAGs. It further implies that cathepsin K represents the
      only lysosomal collagenolytic activity under physiologically relevant conditions.

PMID- 14645230
TI  - Syntaxin-1A binds the nucleotide-binding folds of sulphonylurea receptor 1 to
      regulate the KATP channel.
AB  - ATP-sensitive potassium (KATP) channels in neuron and neuroendocrine cells
      consist of a pore-forming Kir6.2 and regulatory sulfonylurea receptor (SUR1)
      subunits, which are regulated by ATP and ADP. SNARE protein syntaxin 1A (Syn-1A)
      is known to mediate exocytic fusion, and more recently, to also bind and modulate
      membrane-repolarizing voltage-gated K+ channels. Here we show that Syn-1A acts as
      an endogenous regulator of KATP channels capable of closing these channels when
      cytosolic ATP concentrations were lowered. Botulinum neurotoxin C1 cleavage of
      endogenous Syn-1A in insulinoma HIT-T15 cells resulted in the increase in KATP
      currents, which could be subsequently inhibited by recombinant Syn-1A. Whereas
      Syn-1A binds both nucleotide-binding folds (NBF-1 and NBF-2) of SUR1, the
      functional inhibition of KATP channels in rat islet beta-cells by Syn-1A seems to
      be mediated primarily by its interactions with NBF-1. These inhibitory actions of
      Syn-1A can be reversed by physiologic concentrations of ADP and by diazoxide. Syn
      1A therefore acts to fine-tune the regulation of KATP channels during dynamic
      changes in cytosolic ATP and ADP concentrations. These actions of Syn-1A on KATP
      channels contribute to the role of Syn-1A in coordinating the sequence of ionic
      and exocytic events leading to secretion.

PMID- 14645231
TI  - The C-terminal globular domain of the prion protein is necessary and sufficient
      for import into the endoplasmic reticulum.
AB  - The mammalian prion protein (PrP) is composed of an unstructured flexible N
      terminal region and a C-terminal globular domain. We examined the import of PrP
      into the endoplasmic reticulum (ER) of neuronal cells and show that information
      present in the C-terminal globular domain is required for ER import of the N
      terminus. N-terminal fragments of PrP, devoid of structural domains located in
      the C terminus, remained in the cytosol with an uncleaved signal peptide and were
      rapidly degraded by the proteasome. Conversely, the separate C-terminal domain of
      PrP, comprising the highly ordered helix 2-loop-helix 3 motif, was entirely
      imported into the ER. As a consequence, two PrP mutants linked to inherited prion
      disease in humans, PrP-W145Stop and PrP-Q160Stop, were partially retained in the
      cytosol. The cytosolic fraction was characterized by an uncleaved N-terminal
      signal peptide and was degraded by the proteasome. Our study identified a new
      regulatory element in the C-terminal globular domain of PrP necessary and
      sufficient to promote import of PrP into the ER.

PMID- 14645232
TI  - Identification of a novel one-carbon metabolism regulon in Saccharomyces
      cerevisiae.
AB  - Glycine specifically induces genes encoding subunits of the glycine decarboxylase
      complex (GCV1, GCV2, and GCV3), and this is mediated by a fall in cytoplasmic
      levels of 5,10-methylenetetrahydrofolate caused by inhibition of cytoplasmic
      serine hydroxymethyltransferase. Here it is shown that this control system
      extends to genes for other enzymes of one-carbon metabolism and de novo purine
      biosynthesis. Northern analysis of the response to glycine demonstrated that the
      induction of the GCV genes and the induction of other amino acid metabolism genes
      are temporally distinct. The genome-wide response to glycine revealed that
      several other genes are rapidly co-induced with the GCV genes, including SHM2,
      which encodes cytoplasmic serine hydroxymethyltransferase. These results were
      refined by examining transcript levels in an shm2Delta strain (in which
      cytoplasmic 5,10-methylenetetrahydrofolate levels are reduced) and a met13Delta
      strain, which lacks the main methylenetetrahydrofolate reductase activity of
      yeast and is effectively blocked at consumption of 5,10-methylene
      tetrahydrofolate for methionine synthesis. Glycine addition also caused a
      substantial transient disturbance to metabolism, including a sequence of changes
      in induction of amino acid biosynthesis and respiratory chain genes. Analysis of
      the glycine response in the shm2Delta strain demonstrated that apart from the one
      carbon regulon, most of these transient responses were not contingent on a
      disturbance to one-carbon metabolism. The one-carbon response is distinct from
      the Bas1p purine biosynthesis regulon and thus represents the first example of
      transcriptional regulation in response to activated one-carbon status.

PMID- 14645233
TI  - Slit protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive
      signaling pathways in breast cancer cells.
AB  - Slit, which mediates its function by binding to the Roundabout (Robo) receptor,
      has been shown to regulate neuronal and CXCR4-mediated leukocyte migration. Slit
      2 was shown to be frequently inactivated in lung and breast cancers because of
      hypermethylation of its promoter region. Furthermore, the CXCR4/CXCL12 axis has
      been reported recently to be actively involved in breast cancer metastasis to
      target organs such as lymph nodes, lung, and bone. In this study, we sought to
      characterize the effect of Slit (=Slit-2) on the CXCL12/CXCR4-mediated metastatic
      properties of breast cancer cells. We demonstrate here that breast cancer cells
      and tissues derived from breast cancer patients express Robo 1 and 2 receptors.
      We also show that Slit treatment inhibits CXCL12/CXCR4-induced breast cancer cell
      chemotaxis, chemoinvasion, and adhesion, the fundamental components that promote
      metastasis. Slit had no significant effect on the CXCL12-induced internalization
      process of CXCR4. In addition, characterization of signaling events revealed that
      Slit inhibits CXCL12-induced tyrosine phosphorylation of focal adhesion
      components such as RAFTK/Pyk2 at residues 580 and 881, focal adhesion kinase at
      residue 576, and paxillin. We found that Slit also inhibits CXCL12-induced
      phosphatidylinositol 3-kinase, p44/42 MAP kinase, and metalloproteinase 2 and 9
      activities. However, it showed no effect on JNK and p38 MAP kinase activities. To
      our knowledge, this is the first report to analyze in detail the effect of Slit
      on breast cancer cell motility as well as its effect on the critical components
      of the cancer cell chemotactic machinery. Studies of the Slit-Robo complex may
      foster new anti-chemotactic approaches to block cancer cell metastasis.

PMID- 14645234
TI  - Regulation of microtubule destabilizing activity of Op18/stathmin downstream of
      Rac1.
AB  - In the leading edge of migrating cells, a subset of microtubules exhibits net
      growth in a Rac1- and p21-activated kinase-dependent manner. Here, we explore the
      possibility of whether phosphorylation and inactivation of the microtubule
      destabilizing protein Op18/stathmin could be a mechanism regulating microtubule
      dynamics downstream of Rac1 and p21-activated kinases. We find that, in vitro,
      Pak1 phosphorylates Op18/stathmin specifically at serine 16 and inactivates its
      catastrophe promoting activity in biochemical and time lapse microscopy
      microtubule assembly assays. Furthermore, phosphorylation of either serine 16 or
      63 is sufficient to inhibit Op18/stathmin in vitro. In cells, the microtubule
      destabilizing effect of an excess of Op18/stathmin can be partially overcome by
      expression of constitutively active Rac1(Q61L), which is dependent on Pak
      activity, suggesting that the microtubule cytoskeleton can be regulated through
      inactivation of Op18/stathmin downstream of Rac1 and Pak in vivo. However, in
      vivo, Pak1 activity alone is not sufficient to phosphorylate Op18, indicating
      that additional pathways downstream of Rac1 are required for Op18 regulation.

PMID- 14645235
TI  - The coiled-coil domain is the structural determinant for mammalian homologues of
      Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other
      tripartite motif proteins by the proteasome.
AB  - Mammalian homologues of Drosophila Seven in Absentia (SIAHs) target for
      proteasome-mediated degradation several factors involved in cell growth and
      tumorigenesis. Here we show that SIAH-1/2 binds and targets for proteasome
      mediated degradation the putative tumor suppressor and tripartite motif (TRIM)
      family member PML, leading to the loss of its transcriptional co-activating
      properties and a reduction in the number of endogenous PML nuclear bodies.
      Association with PML requires the substrate-binding domain (SBD) of SIAH-1/2
      through an interacting surface apparently distinct from those predicted by the
      structural studies, or shown experimentally to mediate binding to SIAH-associated
      factors. Within PML, the coiled-coil domain is required for Siah- and proteasome
      mediated degradation, and deletions of regions critical for the integrity of this
      region impair the ability of Siah to trigger PML-RAR degradation. Fusion of the
      coiled-coil domain to heterologous proteins resulted in the capacity of mSiah-2
      to target their degradation. All of the TRIM proteins tested were degraded upon
      mSiah-2 overexpression. Finally, we show that the fusion protein PML-RAR (that
      retains the coiled-coil domain), which causes acute promyelocytic leukemias, is
      also a potential substrate of mSiah-2. As a result of mSiah-2 overexpression and
      subsequent degradation of the fusion protein, the arrest in hematopoietic
      differentiation because of expression of PML-RAR is partially rescued. These
      results identify PML and other TRIMs as new factors post-translationally
      regulated by SIAH and involve the coiled-coil region of PML and of other SIAH
      substrates as a novel structural determinant for targeted degradation.

PMID- 14645236
TI  - Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and
      bradykinin B2 receptors.
AB  - Signaling of the apelin, angiotensin, and bradykinin peptides is mediated by G
      protein-coupled receptors related through structure and similarities of
      physiological function. We report nuclear expression as a characteristic of these
      receptors, including a nuclear localization for the apelin receptor in brain and
      cerebellum-derived D283 Med cells and the AT(1) and bradykinin B(2) receptors in
      HEK-293T cells. Immunocytochemical analyses revealed the apelin receptor with
      localization in neuronal nuclei in cerebellum and hypothalamus, exhibiting
      expression in neuronal cytoplasm or in both nuclei and cytoplasm. Confocal
      microscopy of HEK-293T cells revealed the majority of transfected cells displayed
      constitutive nuclear localization of AT(1) and B(2) receptors, whereas apelin
      receptors did not show nuclear localization in these cells. The majority of
      apelin receptor-transfected cerebellum D283 Med cells showed receptor nuclear
      expression. Immunoblot analyses of subcellular-fractionated D283 Med cells
      demonstrated endogenous apelin receptor species in nuclear fractions. In
      addition, an identified nuclear localization signal motif in the third
      intracellular loop of the apelin receptor was disrupted by a substituted
      glutamine in place of lysine. This apelin receptor (K242Q) did not exhibit
      nuclear localization in D283 Med cells. These results demonstrate the following:
      (i) the apelin receptor exhibits nuclear localization in human brain; (ii)
      distinct cell-dependent mechanisms for the nuclear transport of apelin, AT(1),
      and B(2) receptors; and (iii) the disruption of a nuclear localization signal
      sequence disrupts the nuclear translocation of the apelin receptor. This
      discovery of apelin, AT(1), and B(2) receptors with agonist-independent nuclear
      translocation suggests major unanticipated roles for these receptors in cell
      signaling and function.

PMID- 14645238
TI  - E2F and Sp1/Sp3 Synergize but are not sufficient to activate the MYCN gene in
      neuroblastomas.
AB  - Amplification of the MYCN gene, resulting in overexpression of MYCN,
      distinguishes a subset of neuroblastomas with poor prognosis. We recently
      identified MYCN as a target gene of the E2F transcription factors. Here we show
      that Sp1 and Sp3 cooperate with E2F-1 to activate the MYCN promoter. However, in
      a neuroblastoma cell line that does not express MYCN, overexpression of E2F-1 was
      not sufficient to activate the MYCN promoter even in the presence of trichostatin
      A and 5-aza-cytidine. This was because of a failure of E2F-1 to bind to the MYCN
      promoter in these cells, although access of E2F-1 to the inactive MYCN promoter
      was not blocked by a nucleosome. Differences in nucleosomal organization of the
      MYCN promoter in different cell lines did not correlate with gene activation per
      se but with the switch from basal to activated transcription. Binding of E2F and
      Sp1/Sp3 to the MYCN promoter in vivo correlated with acetylation of histones H3
      and H4 and recruitment of RNA polymerase II and the protein acetyltransferase
      Tip60 but not with nucleosome remodeling. Our results define distinct chromatin
      states of the MYCN promoter, indicate that factors in addition to E2F and Sp1/Sp3
      are required to activate MYCN in neuroblastomas, and provide evidence for a novel
      mechanism of controlling access of E2F to selected target genes.

PMID- 14645237
TI  - Developmentally specific role of the CCAAT box in regulation of human gamma
      globin gene expression.
AB  - The CCAAT box is a widespread motif in eukaryotic promoters. In this study we
      demonstrate that the effects of the CCAAT box on gamma-globin gene activation are
      developmentally distinct. Although this promoter element is essential for high
      level gamma gene expression in adult erythropoiesis, it plays little role in
      embryonic erythroid cells. The CCAAT mutation in the human gamma-globin gene
      promoter impairs recruitment of TATA-binding protein (TBP), TFIIB, and RNA
      polymerase II in adult splenic erythroblasts but not in embryonic erythroid
      cells. We also show that the efficiency of gamma gene transcription is correlated
      with recruitment of TBP on the TATA box but that the level of TBP recruitment is
      not nuclear factor Y (NF-Y)-dependent. Our data also suggest that it is unlikely
      that transcriptional stimulation by the CCAAT box is exerted through direct
      protein-protein interaction between NF-Y and TBP.

PMID- 14645239
TI  - Two arginines in the cytoplasmic C-terminal domain are essential for voltage
      dependent regulation of A-type K+ current in the Kv4 channel subfamily.
AB  - Contributions of the C-terminal domain of Kv4.3 to the voltage-dependent gating
      of A-type K+ current (IA) were examined by (i) making mutations in this region,
      (ii) heterologous expression in HEK293 cells, and (iii) detailed voltage clamp
      analyses. Progressive deletions of the C terminus of rat Kv4.3M (to amino acid
      429 from the N terminus) did not markedly change the inactivation time course of
      IA but shifted the voltage dependence of steady state inactivation in the
      negative direction to a maximum of -17 mV. Further deletions (to amino acid 420)
      shifted this parameter in the positive direction, suggesting a critical role for
      the domain 429-420 in the voltage-dependent regulation of IA. There are four
      positively charged amino acids in this domain: Lys423, Lys424, Arg426, and
      Arg429. The replacement of the two arginines with alanines (R2A) resulted in -23
      and -13 mV shifts of inactivation and activation, respectively. Additional
      replacement of the two lysines with alanines did not result in further shifts.
      Single replacements of R426A or R429A induced -15 and -10 mV shifts of
      inactivation, respectively. R2A did not significantly change the inactivation
      rate but did markedly change the voltage dependence of recovery from
      inactivation. These two arginines are conserved in Kv4 subfamily, and alanine
      replacement of Arg429 and Arg432 in Kv4.2 gave essentially the same results.
      These effects of R2A were not modulated by co-expression of the K+ channel beta
      subunit, KChIPs. In conclusion, the two arginines in the cytosolic C-terminal
      domain of alpha-subunits of Kv4 subfamily strongly regulate the voltage
      dependence of channel activation, inactivation, and recovery.

PMID- 14645240
TI  - Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes
      severe neurodevelopmental defects and results in embryonic lethality.
AB  - D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is the first committed
      enzyme of L-serine biosynthesis in the phosphorylated pathway. To determine the
      physiological importance of Phgdh-dependent L-serine biosynthesis in vivo, we
      generated Phgdh-deficient mice using targeted gene disruption in embryonic stem
      cells. The absence of Phgdh led to a drastic reduction of L-serine metabolites
      such as phosphatidyl-L-serine and sphingolipids. Phgdh null embryos have small
      bodies with abnormalities in selected tissues and died after days post-coitum
      13.5. Striking abnormalities were evident in the central nervous system in which
      the Phgdh null mutation culminated in hypoplasia of the telencephalon,
      diencephalon, and mesencephalon; in particular, the olfactory bulbs, ganglionic
      eminence, and cerebellum appeared as indistinct structures. These observations
      demonstrate that the Phgdh-dependent phosphorylated pathway is essential for
      normal embryonic development, especially for brain morphogenesis.

PMID- 14645241
TI  - Interactions between activating signal cointegrator-2 and the tumor suppressor
      retinoblastoma in androgen receptor transactivation.
AB  - Activating signal cointegrator-2 (ASC-2), a cancer-amplified transcription
      coactivator of nuclear receptors and numerous other transcription factors, was
      previously shown to contain two LXXLL motifs, each of which interacts with a
      distinct set of nuclear receptors. In this work, we showed that ASC-2 has an
      indirect, separate binding site for androgen receptor (AR). Interestingly, this
      region overlapped with the direct interaction interfaces with the tumor
      suppressor retinoblastoma (Rb). Although ASC-2 alone stimulated AR
      transactivation in cotransfections of HeLa cells, ectopic expression of Rb
      effected ASC-2 to act as a transcription coactivator of AR in Rb-null Saos2
      cells. These results, along with the previous report in which AR was shown to
      directly interact with Rb (Yeh, S., Miyamoto, H., Nishimura, K., Kang, H.,
      Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang C. (1998) Biochem. Biophys.
      Res. Commun. 248, 361-367), suggest that the AR-ASC-2 interactions in vivo may
      involve Rb. Thus, ASC-2 appears to contain at least three distinct nuclear
      receptor interaction domains.

PMID- 14645242
TI  - Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein
      (XIAP).
AB  - Akt negatively regulates apoptotic pathways at a premitochondrial level through
      phosphorylation and modulation of proteins such as Bad, Forkhead proteins, and
      GSK-3beta. Akt has also been shown to protect cell death at a post-mitochondrial
      level, although its downstream targets have not been well documented. Here, we
      demonstrate that Akt, including AKT1 and AKT2, interacts with and phosphorylates
      X-linked inhibitor of apoptosis protein (XIAP) at residue serine-87 in vitro and
      in vivo. Phosphorylation of XIAP by Akt protects XIAP from ubiquitination and
      degradation in response to cisplatin. Moreover, autoubiquitination of XIAP is
      also inhibited by Akt. Consistent with this, an XIAP mutant introduced into cells
      which mimics the Akt-phosphorylated form (i.e. XIAP-S87D) displays reduced
      ubiquitination and degradation as compared with wild type XIAP. The greater
      stability of XIAP-S87D in cells translated to increased cell survival after
      cisplatin treatment. Conversely, a mutant that could not be phosphorylated by Akt
      (XIAP-S87A) was more rapidly degraded and showed increased cisplatin-induced
      apoptosis. Furthermore, suppression of XIAP by either siRNA or adenovirus of
      antisense of XIAP induced programmed cell death and inhibited Akt-stimulated cell
      survival in ovarian cancer cells. These data identify XIAP as a new downstream
      target of Akt and a potentially important mediator of the effect of Akt on cell
      survival.

PMID- 14645243
TI  - AU-rich elements in the collagenase 3 mRNA mediate stabilization of the
      transcript by cortisol in osteoblasts.
AB  - Collagenase 3 degrades collagen fibrils and is necessary for bone resorption.
      Cortisol increases collagenase 3 mRNA in osteoblasts by stabilizing collagenase 3
      transcripts. To understand mechanisms involved, we used RNA electrophoretic
      mobility shift assay and RNA turnover studies. Cortisol increased the binding of
      Ob cell cytosolic extracts to AU-rich sequences in the collagenase 3 3'
      untranslated region (UTR). No cortisol-dependent protein complexes were formed
      with the coding region or the 5'-UTR. Functional assays, using transient
      transfections of CMV-driven c-fos collagenase 3'-UTR chimeric constructs,
      demonstrated that the 3'-UTR of collagenase 3 stabilizes c-fos mRNA in
      transcriptionally arrested Ob cells, cortisol prolongs the transcript half-life,
      and mutations of AU-rich sequences destabilize c-fos transcripts precluding the
      cortisol effect. Purification of osteoblast cytosolic extracts by
      ultracentrifugation, ion exchange, and RNA affinity chromatography, and
      polyacrylamide gel electrophoresis followed by mass spectroscopy identified
      specific proteins. RNA gel mobility supershift assays demonstrated that vinculin
      and far upstream element (FUSE)-binding protein 2 interacted with collagenase 3
      3'-UTR sequences, and RNA interference demonstrated these proteins altered
      collagenase mRNA stability. In conclusion, AU-rich sequences of the 3'-UTR of
      collagenase 3 and vinculin and FUSE-binding protein 2 regulate collagenase mRNA
      stability in osteoblasts.

PMID- 14645244
TI  - DNA substrate length and surrounding sequence affect the activation-induced
      deaminase activity at cytidine.
AB  - Activation-induced deaminase (AID) is required for both immunoglobulin class
      switch recombination and somatic hypermutation. AID is known to deaminate
      cytidines in single-stranded DNA, but the relationship of this step to the class
      switch or somatic hypermutation processes is not entirely clear. We have studied
      the activity of a recombinant form of the mouse AID protein that was purified
      from a baculovirus expression system. We find that the length of the single
      stranded DNA target is critical to the action of AID at the Cs positioned
      anywhere along the length of the DNA. The DNA sequence surrounding a given C
      influences AID deamination efficiency. AID preferentially deaminates Cs in the
      WRC motif, and additionally has a small but consistent preference for purine at
      the position after the WRC, thereby favoring WRCr (the lowercase r corresponds to
      the smaller impact on activity).

PMID- 14645245
TI  - Fibronectin binds insulin-like growth factor-binding protein 5 and abolishes Its
      ligand-dependent action on cell migration.
AB  - Insulin-like growth factor-binding protein 5 (IGFBP-5) is a secreted protein that
      binds to insulin-like growth factors (IGFs) and modulates IGF actions on cell
      proliferation, differentiation, survival, and motility. IGFBP-5 also regulates
      these cellular events through IGF-independent mechanisms. To elucidate the
      molecular mechanisms governing these diverse actions of IGFBP-5, we screened a
      human cDNA library by a yeast two-hybrid system using IGFBP-5 as bait and
      identified fibronectin (FN) as a potential IGFBP-5-interacting partner. The
      complex formation of IGFBP-5 and FN was established by glutathione S-transferase
      pull-down, solution, and solid phase binding assays using glutathione S
      transferase-IGFBP-5 and native IGFBP-5 in vitro and by co-immunoprecipitation in
      vivo. Binding assay using deletion mutants indicated that the IGFBP-5 C domain
      binds to the 10th and 11th type I repeats of FN. IGFBP-5 potentiated IGF-I
      induced cell migration in FN-null, but not in wild-type, mouse embryonic cells.
      When FN was reintroduced either as an adhesive substrate or in solution to the FN
      null cells, the potentiating effect of IGFBP-5 on IGF-I-induced cell migration
      was abolished. Binding of IGFBP-5 to FN had no effect on the ability of IGFBP-5
      to bind IGF-I, but it increased the proteolytic degradation of IGFBP-5.
      Inhibition of IGFBP-5 proteolysis restored the potentiating effect of IGFBP-5.
      These results suggest that FN and IGFBP-5 bind to each other, and this binding
      negatively regulates the ligand-dependent action of IGFBP-5 by triggering IGFBP-5
      proteolysis.

PMID- 14645246
TI  - The low density lipoprotein receptor-related protein LRP is regulated by membrane
      type-1 matrix metalloproteinase (MT1-MMP) proteolysis in malignant cells.
AB  - We demonstrate that the presentation of LRP and the subsequent uptake of its
      ligands by malignant cells are both strongly regulated by MT1-MMP. Because LRP is
      essential for the clearance of multiple ligands, these findings have important
      implications for many pathophysiological processes including the pericellular
      proteolysis in neoplastic cells as well as the fate of the soluble matrix
      degrading proteases such as MMP-2. MT1-MMP is a key protease in cell invasion and
      a physiological activator of MMP-2. Cellular LRP consists of a non-covalently
      associated 515-kDa extracellular alpha-chain (LRP-515) and an 85-kDa membrane
      spanning beta-chain, and plays a dual role as a multifunctional endocytic
      receptor and a signaling molecule. Through the capture and uptake of several
      soluble proteases, LRP is involved in the regulation of matrix proteolysis. LRP
      515 associates with the MT1-MMP catalytic domain and is highly susceptible to MT1
      MMP proteolysis in vitro. Similar to MT1-MMP, the metalloproteinases MT2-MMP, MT3
      MMP and MT4-MMP also degrade LRP. The N-terminal and C-terminal parts of the LRP
      515 subunit are resistant and susceptible, respectively, to MT1-MMP proteolysis.
      In cells co-expressing LRP and MT1-MMP, the proteolytically competent protease
      decreases the levels of cellular LRP and releases its N-terminal portion in the
      extracellular milieu while the catalytically inert protease co-precipitates with
      LRP. These events implicate MT1-MMP, not only in the activation of MMP-2, but
      also in the mechanisms that control the subsequent fate of MMP-2 in cells and
      tissues.

PMID- 14645247
TI  - Characterization of a mutagenic DNA adduct formed from 1,2-dibromoethane by O6
      alkylguanine-DNA alkyltransferase.
AB  - It has been proposed that the DNA repair protein O6-alkylguanine-DNA
      alkyltransferase increases the mutagenicity of 1,2-dibromoethane by reacting with
      it at its cysteine acceptor site to form a highly reactive half-mustard, which
      can then react with DNA (Liu, L., Pegg, A. E., Williams, K. M., and Guengerich,
      F. P. (2002) J. Biol. Chem. 277, 37920-37928). Incubation of Escherichia coli
      expressed human alkyltransferase with 1,2-dibromoethane and single-stranded
      oligodeoxyribonucleotides led to the formation of covalent transferaseoligo
      complexes. The order of reaction determined was Gua>Thy>Cyt>Ade. Mass
      spectrometry analysis of the tryptic digest of the reaction product indicated
      that some of the adducts led to depurination with the release of the Gly136
      Arg147 peptide cross-linked to a Gua at the N7 position, with the site of
      reaction being the active site Cys145 as established by chromatographic retention
      time and the fragmentation pattern determined by tandem mass spectrometry of a
      synthetic peptide adduct. The alkyltransferase-mediated mutations produced by 1,2
      dibromoethane were predominantly Gua to Ade transitions but, in the spectrum of
      such rifampicin-resistant mutations in the RpoB gene, 20% were Gua to Thy
      transversions. The latter are likely to have arisen from the apurinic site
      generated from the Gua-N7 adduct. Support exists for an additional
      adduct/mutagenic pathway because evidence was obtained for DNA adducts other than
      at the Gua N7 atom and for mutations other than those attributable to
      depurination. Thus, chemical and biological evidence supports the existence of at
      least two alkyltransferase-dependent pathways for 1,2-dibromoethane-induced
      mutagenicity, one involving Gua N7-alkylation by alkyltransferase-S-CH2CH2Br and
      depurination, plus another as yet uncharacterized system(s).

PMID- 14645248
TI  - Phosphotransferase-mediated transport of the osmolyte 2-O-alpha-mannosyl-D
      glycerate in Escherichia coli occurs by the product of the mngA (hrsA) gene and
      is regulated by the mngR (farR) gene product acting as repressor.
AB  - 2-O-alpha-mannosyl-D-glycerate (MGs) has been recognized as an osmolyte in
      hyperthermophilic but not mesophilic prokaryotes. We report that MG is taken up
      and utilized as sole carbon source by Escherichia coli K12, strainMC4100. Uptake
      is mediated by the P-enolpyruvate-dependent phosphotransferase system with the MG
      inducible HrsA (now called MngA) protein as its specific EIIABC complex. The
      apparent Km of MG uptake in induced cells was 10 microm, and the Vmax was 0.65
      nmol/min/10(9) cells. Inverted membrane vesicles harboring plasmid-encoded MngA
      phosphorylated MG in a P-enolpyruvate-dependent manner. A deletion mutant in mngA
      was devoid of MG transport but is complemented by a plasmid harboring mngA.
      Uptake of MG in MC4100 also caused induction of a regulon specifying the uptake
      and the metabolism of galactarate and glucarate controlled by the CdaR activator.
      The ybgG gene (now called mngB) the gene immediately downstream of mngA encodes a
      protein with alpha-mannosidase activity. farR, the gene upstream of mngA (now
      called mngR) had previously been characterized as a fatty acyl-responsive
      regulator; however, deletion of mngR resulted in the up-regulation of only two
      genes, mngA and mngB. The mngR deletion caused constitutive MG transport that
      became MG-inducible after transformation with plasmid expressed mngR. Thus, MngR
      is the regulator (repressor) of the MG transport/metabolism system. Thus, the
      mngR mngA mngB gene cluster encodes an MG utilizing system.

PMID- 14645249
TI  - Characterization of three paralogous members of the Mammalian vaccinia related
      kinase family.
AB  - Members of the novel vaccinia related kinase (VRK) protein family are
      characterized by notable sequence homology to the vaccinia virus-encoded B1
      kinase (vvB1). vvB1 plays an essential role in viral DNA replication, and Boyle
      and Traktman have demonstrated that VRK1 enzymes complement the replication
      defect of a temperature-sensitive viral mutant defective in vvB1 (Boyle, K., and
      Traktman, P. (2004) J. Virol. 78, 1992-2005). This mammalian kinase family
      comprises three members, VRK1, VRK2, and VRK3. We have annotated the gene
      structure for the members of this family and have characterized the enzyme
      activity and subcellular localization for the human and mouse proteins. VRK1
      enzymes show robust autophosphorylation activity and will phosphorylate casein;
      VRK2 enzymes show modest autophosphorylation activity and will also phosphorylate
      casein. The VRK3 proteins have key amino acid substitutions that disrupt
      invariant motifs required for catalytic activity, rendering them enzymatically
      inert. The VRK1 and VRK2 proteins contain COOH-terminal extracatalytic sequences
      that mediate intracellular localization. VRK1 proteins possess a basic nuclear
      localization signal and are indeed nuclear; the extreme C termini of the VRK2
      proteins are highly hydrophobic, and the proteins are membrane-associated and
      colocalize with markers of the endoplasmic reticulum. The NH(2)-terminal region
      of the VRK3s contains a bipartite nuclear localization signal, which directs
      these proteins to the nucleus. Our findings provide the basis for further studies
      of the structure and function of this newly discovered family of protein kinases.

PMID- 14645250
TI  - Domain-specific modification of heparan sulfate by Qsulf1 modulates the binding
      of the bone morphogenetic protein antagonist Noggin.
AB  - We have reported previously that Noggin is a heparin-binding protein and
      associates with the cell surface through heparan sulfate proteoglycans, where it
      remains functional for the binding of bone morphogenetic proteins (BMPs). Here we
      report that the binding of Noggin to the cell surface is highly selective for
      heparan sulfate and that specific structural features are required for the
      interaction. Noggin binds most efficiently to heparin sequences composed of 10 or
      more monosaccharides; N-, 6-O-, and 2-O-sulfates contribute to this interaction.
      In addition, we have shown that the developmentally regulated endosulfatase
      Qsulf1 selectively removes sulfate groups from the 6-O position of sugars within
      the most highly sulfated S domains of heparan sulfate, whereas 6-O-sulfates in
      the NA/NS domains are not substrates for the enzyme. The activity of Qsulf1 in
      cells in culture results in the release of Noggin from the cell surface and a
      restoration of BMP responsiveness to the cells. This shows that Noggin binds to
      the S domains of heparan sulfate and provides evidence that, in addition to
      modulating Wnt signaling in vivo by the release of heparan sulfate bound Wnt,
      Qsulf1 also modulates BMP signaling by the release of surface-bound Noggin.

PMID- 14645251
TI  - Expression of cyclin E renders cyclin D-CDK4 dispensable for inactivation of the
      retinoblastoma tumor suppressor protein, activation of E2F, and G1-S phase
      progression.
AB  - The activation of CDK2-cyclin E in late G1 phase has been shown to play a
      critical role in retinoblastoma protein (pRb) inactivation and G1-S phase
      progression of the cell cycle. The phosphatidylinositol 3-OH-kinase inhibitor
      LY294002 has been shown to block cyclin D1 accumulation, CDK4 activity and, thus,
      G1 progression in alpha-thrombin-stimulated IIC9 cells (Chinese hamster embryonic
      fibroblasts). Our previous results show that expression of cyclin E rescues S
      phase progression in alpha-thrombin-stimulated IIC9 cells treated with LY294002,
      arguing that cyclin E renders CDK4 activity dispensable for G1 progression. In
      this work we investigate the ability of alpha-thrombin-induced CDK2-cyclin E
      activity to inactivate pRb in the absence of prior CDK4-cyclin D1 activity. We
      report that in the absence of CDK4-cyclin D1 activity, CDK2-cyclin E
      phosphorylates pRb in vivo on at least one residue and abolishes pRb binding to
      E2F response elements. We also find that expression of cyclin E rescues E2F
      activation and cyclin A expression in cyclin D kinase-inhibited, alpha-thrombin
      stimulated cells. Furthermore, the rescue of E2F activity, cyclin A expression,
      and DNA synthesis by expression of E can be blocked by the expression of either
      CDK2(D145N) or RbDeltaCDK, a constitutively active mutant of pRb. However,
      restoring four known cyclin E-CDK2 phosphorylation sites to RbDeltaCDK renders it
      susceptible to inactivation in late G1, as assayed by E2F activation, cyclin A
      expression, and S phase progression. These data indicate that CDK2-cyclin E,
      without prior CDK4-cyclin D activity, can phosphorylate and inactivate pRb,
      activate E2F, and induce DNA synthesis.

PMID- 14645252
TI  - Effect of orthophosphate, nucleotide analogues, ADP, and phosphorylation on the
      cytoplasmic domains of Ca(2+)-ATPase from scallop sarcoplasmic reticulum.
AB  - The effects of orthophosphate, nucleotide analogues, ADP, and covalent
      phosphorylation on the tryptic fragmentation patterns of the E1 and E2 forms of
      scallop Ca-ATPase were examined. Sites preferentially cleaved by trypsin in the
      E1 form of the Ca-ATPase were detected in the nucleotide (N) and phosphorylation
      (P) domains, as well as the actuator (A) domain. These sites were occluded in the
      E2 (Ca(2+)-free) form of the enzyme, consistent with mutual protection of the A,
      N, and P domains through their association into a clustered structure. Similar
      protection of cytoplasmic Ca(2+)-dependent tryptic cleavage sites was observed
      when the catalytic binding site for substrate on the E1 form of scallop Ca-ATPase
      was occupied by Pi, AMP-PNP, AMP-PCP, or ADP despite the presence of saturating
      levels of Ca2+. These results suggest that occupation of the catalytic site on E1
      can induce condensation of the cytoplasmic domains to yield a unique structural
      intermediate that may be related to the form of the enzyme in which the active
      site is prepared for phosphoryl transfer. The effect of Pi on the E2 form of the
      scallop Ca-ATPase was also investigated, when it was found that formation of E2-P
      led to extreme resistance toward secondary cleavage by trypsin and stabilization
      of enzymatic activity for long periods of time.

PMID- 14645253
TI  - Mechanism of oxygen sensing by the bacterial transcription factor fumarate
      nitrate reduction (FNR).
AB  - The facultative anaerobe Escherichia coli adopts different metabolic modes in
      response to the availability of oxygen. The global transcriptional regulator FNR
      (fumarate-nitrate reduction) monitors the availability of oxygen in the
      environment. Binding as a homodimer to palindromic sequences of DNA, FNR carries
      a sensory domain, remote from the DNA binding helix-turn-helix motif, which
      responds to oxygen. The sensing mechanism involves the transformation of a [4Fe
      4S](2+) cluster into a [2Fe-2S] form in vitro on reaction with oxygen. Evidence
      is presented to show that this process proceeds by at least two steps, the first,
      an oxidative one, being the formation, on reaction with O(2), of a [3Fe-4S](1+)
      cluster as an intermediate accompanied by the production of hydrogen peroxide.
      This is followed by a slower, non-redox, pseudo-first order step in which the
      [3Fe-4S](1+) form converts to a [2Fe-2S](2+) cluster. This must be accompanied by
      a substantial protein conformational change since the four cysteine ligands that
      bind the two forms of the FeS clusters have different spatial disposition.
      Hydrogen peroxide is also an oxidant of the [4Fe-4S](2+), causing a similar
      cluster transformation to a [2Fe-2S] form. Either the hydrogen peroxide formed on
      reaction with oxygen can be recycled by intracellular catalase or it can be used
      to oxidize further Fe-S clusters. In both cases, the efficacy of oxygen sensing
      by FNR will be increased.

PMID- 14645254
TI  - A novel protein for photosystem I biogenesis.
AB  - Hcf101-1 is a high-chlorophyll-fluorescence (hcf) Arabidopsis mutant that lacks
      photosystem I (1). Photosystem I subunits are synthesized in the mutant but do
      not assemble into a stable complex. hcf101 was isolated by map-based cloning and
      encodes an MRP-like protein with a nucleotide-binding domain. The protein is
      localized in the chloroplast stroma. In green tissue, the Hcf101 level is
      stimulated by light, and the protein is not detectable in roots. Two independent
      knock-out lines, hcf101-2 and hcf101-3, are also impaired in Hcf101 accumulation,
      although to different extents. Like hcf101-1, hcf101-2 and hcf01-3 are hcf
      mutants with impaired photosystem I. Our results indicate that Hcf101 is a novel
      component required for photosystem I biosynthesis.

PMID- 14645255
TI  - Role of the epidermal growth factor receptor in signaling strain-dependent
      activation of the brain natriuretic peptide gene.
AB  - The epidermal growth factor receptor (EGFR) and ectoshedding of heparin-binding
      epidermal growth factor (HBEGF), an EGFR ligand, have been linked to the
      development of cardiac myocyte hypertrophy. However, the precise role that the
      liganded EGFR plays in the transcriptional activation of the gene program that
      accompanies hypertrophy remains undefined. Utilizing the human (h) BNP gene as a
      model of hypertrophy-dependent gene activation, we show that activation of the
      EGFR plays an important role in mediating mechanical strain-dependent stimulation
      of the hBNP promoter. Strain promotes endothelin (ET) generation through NAD(P)H
      oxidase-dependent production of reactive oxygen species. ET in turn induces
      metalloproteinase-mediated cleavage of pro-HBEGF and ectoshedding of HBEGF, which
      activates the EGFR and stimulates hBNP promoter activity. HBEGF also stimulates
      other phenotypic markers of hypertrophy including protein synthesis and
      sarcomeric assembly. The antioxidant N-acetylcysteine or the NAD(P)H oxidase
      inhibitor, apocynin, inhibited strain-dependent activation of the ET-1 promoter,
      HBEGF shedding, and hBNP promoter activation. The metalloproteinase inhibitor, GM
      6001, prevented the induction of HBEGF ectoshedding and the hBNP promoter
      response to strain, suggesting a critical role for the metalloproteinase
      dependent cleavage event in signaling the strain response. These findings suggest
      that metalloproteinase activity as an essential step in this pathway may prove to
      be a relevant therapeutic target in the management of cardiac hypertrophy.

PMID- 14645256
TI  - Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the
      transcriptional activation of human tumor necrosis factor alpha promoter in vivo.
AB  - Tumor necrosis factor alpha (TNF-alpha) contributes to the pathogenesis of both
      acute and chronic inflammatory diseases and has been a target for the development
      of new anti-inflammatory drugs. Shikonins, the naphthoquinone pigments present in
      the root tissues of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae),
      have been reported to exert anti-inflammatory effects both in vitro and in vivo.
      In this study, we evaluated the effects of shikonin and its derivatives on the
      transcriptional activation of human TNF-alpha promoter in a gene gun-transfected
      mouse skin system by using a luciferase reporter gene assay. The crude plant
      extract of L. erythrorhizon as well as derived individual compounds shikonin,
      isobutyryl shikonin, acetyl shikonin, dimethylacryl shikonin and isovaleryl
      shikonin showed significant dose-dependent inhibition of TNF-alpha promoter
      activation. Among the tested compounds, shikonin and isobutyryl shikonin
      exhibited the highest inhibition of TNF-alpha promoter activation and also showed
      significant suppression of transgenic human TNF-alpha mRNA expression and protein
      production. We demonstrated that shikonin-inhibitory response was retained in the
      core TNF-alpha promoter region containing the TATA box and a 48-bp downstream
      sequence relative to the transcription start site. Further our results indicated
      that shikonin suppressed the basal transcription and activator-regulated
      transcription of TNF-alpha by inhibiting the binding of transcription factor IID
      protein complex (TATA box-binding protein) to TATA box. These in vivo results
      suggest that shikonins inhibit the transcriptional activation of the human TNF
      alpha promoter through interference with the basal transcription machinery. Thus,
      shikonins may have clinical potential as anti-inflammatory therapeutics.

PMID- 14645257
TI  - Solution conformation of Lys63-linked di-ubiquitin chain provides clues to
      functional diversity of polyubiquitin signaling.
AB  - Diverse cellular events are regulated by post-translational modification of
      substrate proteins via covalent attachment of one or a chain of ubiquitin
      molecules. The outcome of (poly)ubiquitination depends upon the specific lysine
      residues involved in the formation of polyubiquitin chains. Lys48-linked chains
      act as a universal signal for proteasomal degradation, whereas Lys63-linked
      chains act as a specific signal in several non-degradative processes. Although it
      has been anticipated that functional diversity between alternatively linked
      polyubiquitin chains relies on linkage-dependent differences in chain
      conformation/topology, direct structural evidence in support of this model has
      been lacking. Here we use NMR methods to determine the structure of a Lys63
      linked di-ubiquitin chain. The structure is characterized by an extended
      conformation, with no direct contact between the hydrophobic residues Leu8,
      Ile44, and Val70 on the ubiquitin units. This structure contrasts with the closed
      conformation observed for Lys48-linked di-ubiquitin wherein these residues form
      the interdomain interface (Cook, W. J., Jeffrey, L. C., Carson, M., Zhijian, C.,
      and Pickart, C. M. (1992) J. Biol. Chem. 267, 16467-16471; Varadan, R., Walker,
      O., Pickart, C., and Fushman, D. (2002) J. Mol. Biol. 324, 637-647). Consistent
      with the open conformation of the Lys(63)-linked di-ubiquitin, our binding
      studies show that both ubiquitin domains in this chain can bind a ubiquitin
      associated domain from HHR23A independently and in a mode similar to that for
      mono-ubiquitin. In contrast, Lys48-linked di-ubiquitin binds in a different,
      higher affinity mode that has yet to be determined. This is the first
      experimental evidence that alternatively linked polyubiquitin chains adopt
      distinct conformations.

PMID- 14645258
TI  - A constituent of green tea, epigallocatechin-3-gallate, activates endothelial
      nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent
      protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent
      vasorelaxation.
AB  - Epidemiological studies suggest that tea catechins may reduce the risk of
      cardiovascular disease, but the mechanisms of benefit have not been determined.
      The objective of the present study was to investigate the effects of
      epigallocatechin-3-gallate (EGCG), the major constituent of green tea, on
      vasorelaxation and on eNOS expression and activity in endothelial cells. EGCG (1
      50 microm) induced dose-dependent vasodilation in rat aortic rings. Vasodilation
      was abolished by pretreatment with Ng-nitro L-arginine methyl ester. In bovine
      aortic endothelial cells, EGCG increased endothelial nitric oxide (eNOS) activity
      dose-dependently after 15 min. Treatment with EGCG induced a sustained activation
      of Akt, ERK1/2, and eNOS Ser1179 phosphorylation. Inhibition of extracellular
      signal-regulated kinase (ERK)1/2 had no influence on eNOS activity or Ser1179
      phosphorylation. Simultaneous treatment of cells with selective inhibitors for
      cAMP-dependent protein kinase (PKA) and Akt completely prevented the increase in
      eNOS activity by EGCG after 15 min, indicating that both kinases act in concert.
      Specific phosphatidylinositol-3-OH-kinase inhibitors yielded identical results.
      Akt inhibition prevented eNOS Ser1179 phosphorylation, whereas inhibition of PKA
      did not influence Akt and eNOS Ser1179 phosphorylation. Pretreatment of
      endothelial cells with EGCG for 4 h markedly enhanced the increase in eNOS
      activity stimulated by Ca-ionomycin, suggesting that Akt accounts for prolonged
      eNOS activation. Treatment of cells for 72 h with EGCG did not change eNOS
      protein levels. Our results indicate that EGCG-induced endothelium-dependent
      vasodilation is primarily based on rapid activation of eNOS by a
      phosphatidylinositol 3-kinase-, PKA-, and Akt-dependent increase in eNOS
      activity, independently of an altered eNOS protein content.

PMID- 14645260
TI  - Deregulation and mislocalization of the cytokinesis regulator ECT2 activate the
      Rho signaling pathways leading to malignant transformation.
AB  - The human ECT2 protooncogene encodes a guanine nucleotide exchange factor for the
      Rho GTPases and regulates cytokinesis. Although the oncogenic form of ECT2
      contains an N-terminal truncation, it is not clear how the structural abnormality
      of ECT2 causes malignant transformation. Here we show that both the removal of
      the negative regulatory domain and alteration of subcellular localization are
      required to induce the oncogenic activity of ECT2. The transforming activity of
      oncogenic ECT2 was strongly inhibited by dominant negative Rho GTPases,
      suggesting the involvement of Rho GTPases in ECT2 transformation. Although
      deletion of the N-terminal cell cycle regulator-related domain (N) of ECT2 did
      not activate its transforming activity, removal of the small central domain (S),
      which contains two nuclear localization signals (NLSs), significantly induced the
      activity. The ECT2 N domain interacted with the catalytic domain and
      significantly inhibited the focus formation by oncogenic ECT2. Interestingly, the
      introduction of the NLS mutations in the S domain of N-terminally truncated ECT2
      dramatically induced the transforming activity of this otherwise non-oncogenic
      derivative. Among the known Rho GTPases expressed in NIH 3T3 cells, RhoA was
      predominantly activated by oncogenic ECT2 in vivo. Therefore, the mislocalization
      of structurally altered ECT2 might cause the untimely activation of cytoplasmic
      Rho GTPases leading to the malignant transformation.

PMID- 14645259
TI  - Evidence that receptor activator of nuclear factor (NF)-kappaB ligand can
      suppress cell proliferation and induce apoptosis through activation of a NF
      kappaB-independent and TRAF6-dependent mechanism.
AB  - The receptor activator of NF-kappaB ligand (RANKL), a recently identified member
      of the tumor necrosis factor (TNF) superfamily, has been shown to induce
      osteoclastogenesis and dendritic cell survival. Most members of the TNF
      superfamily suppress cell proliferation and induce apoptosis, but whether RANKL
      does so is not known. We demonstrate that treatment of monocyte RAW 264.7 cells
      with RANKL induces dose-dependent growth inhibition (IC50 = 10 ng/ml) as
      determined by dye uptake and [3H]thymidine incorporation methods. Suppression of
      RANKL-induced NF-kappaB activation by dominant-negative IkappaBalpha or by the
      NEMO-peptide had no effect on RANKL-induced cell growth inhibition. Inhibition of
      RANKL-induced JNK activation, however, abolished the RANKL-induced apoptosis.
      Suppression of interaction of RANK with TRAF6 by TRAF6-binding peptide abrogated
      the anti-proliferative effects of RANKL, suggesting the critical role of TRAF6.
      Flow cytometric analysis of cells treated with RANKL showed accumulation of cells
      in G0/G1 phase of the cell cycle, and this accumulation correlated with a decline
      in the levels of cyclin D1, cyclin D3, and cyclin E and an increase in cyclin
      dependent kinase inhibitor p27 (Kip). Flow cytometric analysis showed the
      presence of annexin V-positive cells in cultures treated with RANKL. RANKL
      induced apoptosis was further confirmed using calcein AM/ethidium homodimer-1 dye
      and cleavage of poly(ADP-ribose) polymerase (PARP), procaspase 3, and procaspase
      9; benzyloxycarbonyl-VAD, the pancaspase inhibitor, suppressed the PARP cleavage.
      Thus, overall, our studies indicate that RANKL can inhibit cell proliferation and
      induce apoptosis through a TRAF-6-dependent but NF-kappaB-independent mechanism.

PMID- 14645261
TI  - It is all about metabolic fluxes.

PMID- 14645262
TI  - Learning from nature's drug factories: nonribosomal synthesis of macrocyclic
      peptides.

PMID- 14645263
TI  - The growth advantage in stationary-phase phenotype conferred by rpoS mutations is
      dependent on the pH and nutrient environment.
AB  - Escherichia coli cells that are aged in batch culture display an increased
      fitness referred to as the growth advantage in stationary phase, or GASP,
      phenotype. A common early adaptation to this culture environment is a mutant rpoS
      allele, such as rpoS819, that results in attenuated RpoS activity. However, it is
      important to note that during long-term batch culture, environmental conditions
      are in flux. To date, most studies of the GASP phenotype have focused on
      identifying alleles that render an advantage in a specific environment, Luria
      Bertani broth (LB) batch culture. To determine what role environmental conditions
      play in rendering relative fitness advantages to E. coli cells carrying either
      the wild-type or rpoS819 alleles, we performed competitions under a variety of
      culture conditions in which either the available nutrients, the pH, or both were
      manipulated. In LB medium, we found that while the rpoS819 allele confers a
      strong competitive fitness advantage at basic pH, it confers a reduced advantage
      under neutral conditions, and it is disadvantageous under acidic conditions.
      Similar results were found using other media. rpoS819 conferred its greatest
      advantage in basic minimal medium in which either glucose or Casamino Acids were
      the sole source of carbon and energy. In acidic medium supplemented with either
      Casamino Acids or glucose, the wild-type allele conferred a slight advantage. In
      addition, populations were dynamic under all pH conditions tested, with neither
      the wild-type nor mutant rpoS alleles sweeping a culture. We also found that the
      strength of the fitness advantage gained during a 10-day incubation is pH
      dependent.

PMID- 14645264
TI  - Responses of the central metabolism in Escherichia coli to phosphoglucose
      isomerase and glucose-6-phosphate dehydrogenase knockouts.
AB  - The responses of Escherichia coli central carbon metabolism to knockout mutations
      in phosphoglucose isomerase and glucose-6-phosphate (G6P) dehydrogenase genes
      were investigated by using glucose- and ammonia-limited chemostats. The metabolic
      network structures and intracellular carbon fluxes in the wild type and in the
      knockout mutants were characterized by using the complementary methods of flux
      ratio analysis and metabolic flux analysis based on [U-(13)C]glucose labeling and
      two-dimensional nuclear magnetic resonance (NMR) spectroscopy of cellular amino
      acids, glycerol, and glucose. Disruption of phosphoglucose isomerase resulted in
      use of the pentose phosphate pathway as the primary route of glucose catabolism,
      while flux rerouting via the Embden-Meyerhof-Parnas pathway and the nonoxidative
      branch of the pentose phosphate pathway compensated for the G6P dehydrogenase
      deficiency. Furthermore, additional, unexpected flux responses to the knockout
      mutations were observed. Most prominently, the glyoxylate shunt was found to be
      active in phosphoglucose isomerase-deficient E. coli. The Entner-Doudoroff
      pathway also contributed to a minor fraction of the glucose catabolism in this
      mutant strain. Moreover, although knockout of G6P dehydrogenase had no
      significant influence on the central metabolism under glucose-limited conditions,
      this mutation resulted in extensive overflow metabolism and extremely low
      tricarboxylic acid cycle fluxes under ammonia limitation conditions.

PMID- 14645266
TI  - Development of a physical and genetic map of the virulent Wolbachia strain
      wMelPop.
AB  - We report here the construction of a physical and genetic map of the virulent
      Wolbachia strain, wMelPop. This map was determined by ordering 28 chromosome
      fragments that resulted from digestion with the restriction endonucleases FseI,
      ApaI, SmaI, and AscI and were resolved by pulsed-field gel electrophoresis.
      Southern hybridization was done with 53 Wolbachia-specific genes as probes in
      order to determine the relative positions of these restriction fragments and use
      them to serve as markers. Comparison of the resulting map with the whole genome
      sequence of the closely related benign Wolbachia strain, wMel, shows that the two
      genomes are largely conserved in gene organization with the exception of a single
      inversion in the chromosome.

PMID- 14645265
TI  - FimX, a multidomain protein connecting environmental signals to twitching
      motility in Pseudomonas aeruginosa.
AB  - Twitching motility is a form of surface translocation mediated by the extension,
      tethering, and retraction of type IV pili. Three independent Tn5-B21 mutations of
      Pseudomonas aeruginosa with reduced twitching motility were identified in a new
      locus which encodes a predicted protein of unknown function annotated PA4959 in
      the P. aeruginosa genome sequence. Complementation of these mutants with the wild
      type PA4959 gene, which we designated fimX, restored normal twitching motility.
      fimX mutants were found to express normal levels of pilin and remained sensitive
      to pilus-specific bacteriophages, but they exhibited very low levels of surface
      pili, suggesting that normal pilus function was impaired. The fimX gene product
      has a molecular weight of 76,000 and contains four predicted domains that are
      commonly found in signal transduction proteins: a putative response regulator
      (CheY-like) domain, a PAS-PAC domain (commonly involved in environmental
      sensing), and DUF1 (or GGDEF) and DUF2 (or EAL) domains, which are thought to be
      involved in cyclic di-GMP metabolism. Red fluorescent protein fusion experiments
      showed that FimX is located at one pole of the cell via sequences adjacent to its
      CheY-like domain. Twitching motility in fimX mutants was found to respond
      relatively normally to a range of environmental factors but could not be
      stimulated by tryptone and mucin. These data suggest that fimX is involved in the
      regulation of twitching motility in response to environmental cues.

PMID- 14645267
TI  - Suppression of factor-dependent transcription termination by antiterminator RNA.
AB  - Nascent transcripts of the phage HK022 put sites modify the transcription
      elongation complex so that it terminates less efficiently at intrinsic
      transcription terminators and accelerates through pause sites. We show here that
      the modification also suppresses termination in vivo at two factor-dependent
      terminators, one that depends on the bacterial Rho protein and a second that
      depends on the HK022-encoded Nun protein. Suppression was efficient when the
      termination factors were present at physiological levels, but an increase in the
      intracellular concentration of Nun increased termination both in the presence and
      absence of put. put-mediated antitermination thus shows no apparent terminator
      specificity, suggesting that put inhibits a step that is common to termination at
      the different types of terminator.

PMID- 14645268
TI  - XopC and XopJ, two novel type III effector proteins from Xanthomonas campestris
      pv. vesicatoria.
AB  - Pathogenicity of the gram-negative plant pathogen Xanthomonas campestris pv.
      vesicatoria depends on a type III secretion (TTS) system which translocates
      bacterial effector proteins into the plant cell. Previous transcriptome analysis
      identified a genome-wide regulon of putative virulence genes that are coexpressed
      with the TTS system. In this study, we characterized two of these genes, xopC and
      xopJ. Both genes encode Xanthomonas outer proteins (Xops) that were shown to be
      secreted by the TTS system. In addition, type III-dependent translocation of both
      proteins into the plant cell was demonstrated using the AvrBs3 effector domain as
      a reporter. XopJ belongs to the AvrRxv/YopJ family of effector proteins from
      plant and animal pathogenic bacteria. By contrast, XopC does not share
      significant homology to proteins in the database. Sequence analysis revealed that
      the xopC locus contains several features that are reminiscent of pathogenicity
      islands. Interestingly, the xopC region is flanked by 62-bp inverted repeats that
      are also associated with members of the Xanthomonas avrBs3 effector family.
      Besides xopC, a second gene of the locus, designated hpaJ, was shown to be
      coexpressed with the TTS system. hpaJ encodes a protein with similarity to
      transglycosylases and to the Pseudomonas syringae pv. maculicola protein HopPmaG.
      HpaJ secretion and translocation by the X. campestris pv. vesicatoria TTS system
      was not detectable, which is consistent with its predicted Sec signal and a
      putative function as transglycosylase in the bacterial periplasm.

PMID- 14645269
TI  - Alterations of cell wall structure and metabolism accompany reduced
      susceptibility to vancomycin in an isogenic series of clinical isolates of
      Staphylococcus aureus.
AB  - A series of isogenic methicillin-resistant Staphylococcus aureus isolates
      recovered from a bacteremic patient were shown to acquire gradually increasing
      levels of resistance to vancomycin during chemotherapy with the drug (K.
      Sieradzki, T. Leski, L. Borio, J. Dick, and A. Tomasz, J. Clin. Microbiol.
      41:1687-1693, 2003). We compared properties of the earliest (parental) vancomycin
      susceptible isolate, JH1 (MIC, 1 microg/ml), to two late (progeny) isolates, JH9
      and JH14 (vancomycin MIC, 8 microg/ml). The resistant isolates produced
      abnormally thick cell walls and poorly separated cells when grown in antibiotic
      free medium. Chemical analysis of the resistant isolates showed decreased cross
      linkage of the peptidoglycan and drastically reduced levels of PBP4 as determined
      by the fluorographic assay. Resistant isolates showed reduced rates of cell wall
      turnover and autolysis. In vitro hydrolysis of resistant cell walls by autolytic
      extracts prepared from either susceptible or resistant strains was also slow, and
      this abnormality could be traced to a quantitative (or qualitative) change in the
      wall teichoic acid component of resistant isolates. Some change in the structure
      and/or metabolism of teichoic acids appears to be an important component of the
      mechanism of decreased susceptibility to vancomycin in S. aureus.

PMID- 14645270
TI  - Interaction between the H2 sensor HupUV and the histidine kinase HupT controls
      HupSL hydrogenase synthesis in Rhodobacter capsulatus.
AB  - The photosynthetic bacterium Rhodobacter capsulatus contains two
      [NiFe]hydrogenases: an energy-generating hydrogenase, HupSL, and a regulatory
      hydrogenase, HupUV. The synthesis of HupSL is specifically activated by H(2)
      through a signal transduction cascade comprising three proteins: the H(2)-sensing
      HupUV protein, the histidine kinase HupT, and the transcriptional regulator HupR.
      Whereas a phosphotransfer between HupT and HupR was previously demonstrated,
      interaction between HupUV and HupT was only hypothesized based on in vivo
      analyses of mutant phenotypes. To visualize the in vitro interaction between
      HupUV and HupT proteins, a six-His (His(6))-HupU fusion protein and the HupV
      protein were coproduced by using a homologous expression system. The two proteins
      copurified as a His(6)-HupUHupV complex present in dimeric and tetrameric forms,
      both of which had H(2) uptake activity. We demonstrated that HupT and HupUV
      interact and form stable complexes that could be separated on a native gel.
      Interaction was also monitored with surface plasmon resonance technology and was
      shown to be insensitive to salt concentration and pH changes, suggesting that the
      interactions involve hydrophobic residues. As expected, H(2) affects the
      interaction between HupUV and HupT, leading to a weakening of the interaction,
      which is independent of the phosphate status of HupT. Several forms of HupT were
      tested for their ability to interact with HupUV and to complement hupT mutants.
      Strong interaction with HupUV was obtained with the isolated PAS domain of HupT
      and with inactive HupT mutated in the phosphorylable histidine residue, but only
      the wild-type HupT protein was able to restore normal H(2) regulation.

PMID- 14645271
TI  - Propane monooxygenase and NAD+-dependent secondary alcohol dehydrogenase in
      propane metabolism by Gordonia sp. strain TY-5.
AB  - A new isolate, Gordonia sp. strain TY-5, is capable of growth on propane and n
      alkanes with C(13) to C(22) carbon chains as the sole source of carbon. In whole
      cell reactions, significant propane oxidation to 2-propanol was detected. A gene
      cluster designated prmABCD, which encodes the components of a putative dinuclear
      iron-containing multicomponent monooxygenase, including the large and small
      subunits of the hydroxylase, an NADH-dependent acceptor oxidoreductase, and a
      coupling protein, was cloned and sequenced. A mutant with prmB disrupted
      (prmB::Kan(r)) lost the ability to grow on propane, and Northern blot analysis
      revealed that polycistronic transcription of the prm genes was induced during its
      growth on propane. These results indicate that the prmABCD gene products play an
      essential role in propane oxidation by the bacterium. Downstream of the prm
      genes, an open reading frame (adh1) encoding an NAD(+)-dependent secondary
      alcohol dehydrogenase was identified, and the protein was purified and
      characterized. The Northern blot analysis results and growth properties of a
      disrupted mutant (adh1::Kan(r)) indicate that Adh1 plays a major role in propane
      metabolism. Two additional NAD(+)-dependent secondary alcohol dehydrogenases
      (Adh2 and Adh3) were also found to be involved in 2-propanol oxidation. On the
      basis of these results, we conclude that Gordonia sp. strain TY-5 oxidizes
      propane by monooxygenase-mediated subterminal oxidation via 2-propanol.

PMID- 14645272
TI  - Functional domains of the RhlR transcriptional regulator of Pseudomonas
      aeruginosa.
AB  - The RhlR transcriptional regulator of Pseudomonas aeruginosa, along with its
      cognate autoinducer, N-butyryl homoserine lactone (C(4)-HSL), regulates gene
      expression in response to cell density. With an Escherichia coli LexA-based
      protein interaction system, we demonstrated that RhlR multimerized and that the
      degree of multimerization was dependent on the C(4)-HSL concentration. Studies
      with an E. coli lasB::lacZ lysogen demonstrated that RhlR multimerization was
      necessary for it to function as a transcriptional activator. Deletion analysis of
      RhlR indicated that the N-terminal domain of the protein is necessary for C(4)
      HSL binding. Single amino acid substitutions in the C-terminal domain of RhlR
      generated mutant RhlR proteins that had the ability to bind C(4)-HSL and
      multimerize but were unable to activate lasB expression, demonstrating that the C
      terminal domain is important for target gene activation. Single amino acid
      substitutions in both the N-terminal and C-terminal domains of RhlR demonstrated
      that both domains possess residues involved in multimerization. RhlR with a C
      terminal deletion and an RhlR site-specific mutant form that possessed
      multimerization but not transcriptional activation capabilities were able to
      inhibit the ability of wild-type RhlR to activate rhlA expression in P.
      aeruginosa. We conclude that C(4)-HSL binding is necessary for RhlR
      multimerization and that RhlR functions as a multimer in P. aeruginosa.

PMID- 14645273
TI  - Transcriptional regulation and posttranslational activity of the betaine
      transporter BetL in Listeria monocytogenes are controlled by environmental
      salinity.
AB  - While the genetic elements contributing to the salinity tolerance of Listeria
      monocytogenes have been well characterized, the regulatory signals and responses
      (genetic and/or biochemical) that govern these mechanisms have yet to be
      elucidated. Encoded by betL, the first genetic element to be linked to listerial
      osmotolerance, the secondary betaine uptake system BetL is a member of the
      betaine-carnitine-choline transporter family. Preceded by consensus sigma(A)- and
      sigma(B)-dependent promoter sites, betL is constitutively expressed and
      transcriptionally up-regulated in response to salt stress. The nisin-controlled
      expression system was used to achieve salinity-independent, controlled betL
      expression in Listeria. In the absence of NaCl-activated transcriptional control,
      BetL activity was found to be a function of environmental salinity, showing
      optimal activity in buffer supplemented with 1 to 2% NaCl (osmolality, 417 to 719
      mosmol/kg). In addition, BetL was activated rapidly (half-life, 2 min) in
      response to an osmotic upshift imposed by adding 2% NaCl to 50 mM potassium
      phosphate buffer.

PMID- 14645274
TI  - FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR
      regulatory mechanism.
AB  - The farAB operon of Neisseria gonorrhoeae encodes an efflux pump which mediates
      gonococcal resistance to antibacterial fatty acids. It was previously observed
      that expression of the farAB operon was positively regulated by MtrR, which is a
      repressor of the mtrCDE-encoded efflux pump system (E.-H. Lee and W. M. Shafer,
      Mol. Microbiol. 33:839-845, 1999). This regulation was believed to be indirect
      since MtrR did not bind to the farAB promoter. In this study, computer analysis
      of the gonococcal genome sequence database, lacZ reporter fusions, and gel
      mobility shift assays were used to elucidate the regulatory mechanism by which
      expression of the farAB operon is modulated by MtrR in gonococci. We identified a
      regulatory protein belonging to the MarR family of transcriptional repressors and
      found that it negatively controls expression of farAB by directly binding to the
      farAB promoter. We designated this regulator FarR to signify its role in
      regulating the farAB operon. We found that MtrR binds to the farR promoter,
      thereby repressing farR expression. Hence, MtrR regulates farAB in a positive
      fashion by modulating farR expression. This MtrR regulatory cascade seems to play
      an important role in adjusting levels of the FarAB and MtrCDE efflux pumps to
      prevent their excess expression in gonococci.

PMID- 14645275
TI  - YmoA negatively regulates expression of invasin from Yersinia enterocolitica.
AB  - inv encodes invasin, which is the primary invasion factor of Yersinia
      enterocolitica. inv expression in vitro is regulated in response to temperature,
      pH, and growth phase. In vitro, inv is maximally expressed at 26 degrees C and
      repressed at 37 degrees C at neutral pH but, when the pH of the media is adjusted
      to 5.5, levels of inv expression at 37 degrees C are comparable to those at 26
      degrees C. A previous genetic screen for regulators of inv identified RovA, which
      was found to be required for activation of inv in vitro under all conditions
      tested as well as in vivo. Here we describe a screen that has identified a
      negative regulator of inv expression, ymoA. The ymoBA locus was identified by
      transposon mutagenesis as a repressor of inv expression in vitro at 37 degrees C
      at neutral pH. This mutant shows increased inv expression at 37 degrees C. The
      mutant can be fully complemented for inv expression by a plasmid expressing ymoA.
      These results indicate that YmoA plays a role in the negative regulation of inv.

PMID- 14645276
TI  - Formaldehyde-detoxifying role of the tetrahydromethanopterin-linked pathway in
      Methylobacterium extorquens AM1.
AB  - The facultative methylotroph Methylobacterium extorquens AM1 possesses two pterin
      dependent pathways for C(1) transfer between formaldehyde and formate, the
      tetrahydrofolate (H(4)F)-linked pathway and the tetrahydromethanopterin (H(4)MPT)
      linked pathway. Both pathways are required for growth on C(1) substrates;
      however, mutants defective for the H(4)MPT pathway reveal a unique phenotype of
      being inhibited by methanol during growth on multicarbon compounds such as
      succinate. It has been previously proposed that this methanol-sensitive phenotype
      is due to the inability to effectively detoxify formaldehyde produced from
      methanol. Here we present a comparative physiological characterization of four
      mutants defective in the H(4)MPT pathway and place them into three different
      phenotypic classes that are concordant with the biochemical roles of the
      respective enzymes. We demonstrate that the analogous H(4)F pathway present in M.
      extorquens AM1 cannot fulfill the formaldehyde detoxification function, while a
      heterologously expressed pathway linked to glutathione and NAD(+) can
      successfully substitute for the H(4)MPT pathway. Additionally, null mutants were
      generated in genes previously thought to be essential, indicating that the
      H(4)MPT pathway is not absolutely required during growth on multicarbon
      compounds. These results define the role of the H(4)MPT pathway as the primary
      formaldehyde oxidation and detoxification pathway in M. extorquens AM1.

PMID- 14645277
TI  - Purification of the formate-tetrahydrofolate ligase from Methylobacterium
      extorquens AM1 and demonstration of its requirement for methylotrophic growth.
AB  - The serine cycle methylotroph Methylobacterium extorquens AM1 contains two pterin
      dependent pathways for C(1) transfers, the tetrahydrofolate (H(4)F) pathway and
      the tetrahydromethanopterin (H(4)MPT) pathway, and both are required for growth
      on C(1) compounds. With the exception of formate-tetrahydrofolate ligase (FtfL,
      alternatively termed formyl-H(4)F synthetase), all of the genes encoding the
      enzymes comprising these two pathways have been identified, and the corresponding
      gene products have been purified and characterized. We present here the
      purification and characterization of FtfL from M. extorquens AM1 and the
      confirmation that this enzyme is encoded by an ftfL homolog identified previously
      through transposon mutagenesis. Phenotypic analyses of the ftfL mutant strain
      demonstrated that FtfL activity is required for growth on C(1) compounds. Unlike
      mutants defective for the H(4)MPT pathway, the ftfL mutant strain does not
      exhibit phenotypes indicative of defective formaldehyde oxidation. Furthermore,
      the ftfL mutant strain remained competent for wild-type conversion of
      [(14)C]methanol to [(14)C]CO(2). Collectively, these data confirm our previous
      presumptions that the H(4)F pathway is not the key formaldehyde oxidation pathway
      in M. extorquens AM1. Rather, our data suggest an alternative model for the role
      of the H(4)F pathway in this organism in which it functions to convert formate to
      methylene H(4)F for assimilatory metabolism.

PMID- 14645278
TI  - Competence-induced cells of Streptococcus pneumoniae lyse competence-deficient
      cells of the same strain during cocultivation.
AB  - Several streptococcal species are able to take up naked DNA from the environment
      and integrate it into their genomes by homologous recombination. This process is
      called natural transformation. In Streptococcus pneumoniae and related
      streptococcal species, competence for natural transformation is induced by a
      peptide pheromone through a quorum-sensing mechanism. Recently we showed that
      induction of the competent state initiates lysis and release of DNA from a
      subfraction of the bacterial population and that the efficiency of this process
      is influenced by cell density. Here we have further investigated the nature of
      this cell density-dependent release mechanism. Interestingly, we found that
      competence-induced pneumococci lysed competence-deficient cells of the same
      strain during cocultivation and that the efficiency of this heterolysis increased
      as the ratio of competent to noncompetent cells increased. Furthermore, our
      results indicate that the lysins made by competent pneumococci are not released
      into the growth medium. More likely, they are anchored to the surface of the
      competent cells by choline-binding domains and cause lysis of noncompetent
      pneumococci through cell-to-cell contact.

PMID- 14645279
TI  - The CroRS two-component regulatory system is required for intrinsic beta-lactam
      resistance in Enterococcus faecalis.
AB  - Enterococcus faecalis produces a specific penicillin-binding protein (PBP5) that
      mediates high-level resistance to the cephalosporin class of beta-lactam
      antibiotics. Deletion of a locus encoding a previously uncharacterized two
      component regulatory system of E. faecalis (croRS) led to a 4,000-fold reduction
      in the MIC of the expanded-spectrum cephalosporin ceftriaxone. The cytoplasmic
      domain of the sensor kinase (CroS) was purified and shown to catalyze ATP
      dependent autophosphorylation followed by transfer of the phosphate to the mated
      response regulator (CroR). The croR and croS genes were cotranscribed from a
      promoter (croRp) located in the rrnC-croR intergenic region. A putative seryl
      tRNA synthetase gene (serS) located immediately downstream from croS did not
      appear to be a target of CroRS regulation or to play a role in ceftriaxone
      resistance. A plasmid-borne croRp-lacZ fusion was trans-activated by the CroRS
      system in response to the presence of ceftriaxone in the culture medium. The
      fusion was also induced by representatives of other classes of beta-lactam
      antibiotics and by inhibitors of early and late steps of peptidoglycan synthesis.
      The croRS null mutant produced PBP5, and expression of an additional copy of pbp5
      under the control of a heterologous promoter did not restore ceftriaxone
      resistance. Deletion of croRS was not associated with any defect in the synthesis
      of the nucleotide precursor UDP-MurNAc-pentapeptide or of the D-Ala(4)-->L-Ala-L
      Ala-Lys(3) peptidoglycan cross-bridge. Thus, the croRS mutant was susceptible to
      ceftriaxone despite the production of PBP5 and the synthesis of wild-type
      peptidoglycan precursors. These observations constitute the first description of
      regulatory genes essential for PBP5-mediated beta-lactam resistance in
      enterococci.

PMID- 14645280
TI  - A new pathway for salvaging the coenzyme B12 precursor cobinamide in archaea
      requires cobinamide-phosphate synthase (CbiB) enzyme activity.
AB  - The ability of archaea to salvage cobinamide has been under question because
      archaeal genomes lack orthologs to the bacterial nucleoside triphosphate:5'
      deoxycobinamide kinase enzyme (cobU in Salmonella enterica). The latter activity
      is required for cobinamide salvaging in bacteria. This paper reports evidence
      that archaea salvage cobinamide from the environment by using a pathway different
      from the one used by bacteria. These studies demanded the functional
      characterization of two genes whose putative function had been annotated based
      solely on their homology to the bacterial genes encoding adenosylcobyric acid and
      adenosylcobinamide-phosphate synthases (cbiP and cbiB, respectively) of S.
      enterica. A cbiP mutant strain of the archaeon Halobacterium sp. strain NRC-1 was
      auxotrophic for adenosylcobyric acid, a known intermediate of the de novo
      cobamide biosynthesis pathway, but efficiently salvaged cobinamide from the
      environment, suggesting the existence of a salvaging pathway in this archaeon. A
      cbiB mutant strain of Halobacterium was auxotrophic for adenosylcobinamide-GDP, a
      known de novo intermediate, and did not salvage cobinamide. The results of the
      nutritional analyses of the cbiP and cbiB mutants suggested that the entry point
      for cobinamide salvaging is adenosylcobyric acid. The data are consistent with a
      salvaging pathway for cobinamide in which an amidohydrolase enzyme cleaves off
      the aminopropanol moiety of adenosylcobinamide to yield adenosylcobyric acid,
      which is converted by the adenosylcobinamide-phosphate synthase enzyme to
      adenosylcobinamide-phosphate, a known intermediate of the de novo biosynthetic
      pathway. The existence of an adenosylcobinamide amidohydrolase enzyme would
      explain the lack of an adenosylcobinamide kinase in archaea.

PMID- 14645281
TI  - GacA regulates symbiotic colonization traits of Vibrio fischeri and facilitates a
      beneficial association with an animal host.
AB  - The GacS/GacA two-component system regulates the expression of bacterial traits
      during host association. Although the importance of GacS/GacA as a regulator of
      virulence is well established, its role in benign associations is not clear, as
      mutations in either the gacS or gacA gene have little impact on the success of
      colonization in nonpathogenic associations studied thus far. Using as a model the
      symbiotic association of the bioluminescent marine bacterium Vibrio fischeri with
      its animal host, the Hawaiian bobtail squid, Euprymna scolopes, we investigated
      the role of GacA in this beneficial animal-microbe interaction. When grown in
      culture, gacA mutants were defective in several traits important for symbiosis,
      including luminescence, growth in defined media, growth yield, siderophore
      activity, and motility. However, gacA mutants were not deficient in production of
      acylated homoserine lactone signals or catalase activity. The ability of the gacA
      mutants to initiate squid colonization was impaired but not abolished, and they
      reached lower-than-wild-type population densities within the host light organ. In
      contrast to their dark phenotype in culture, gacA mutants that reached population
      densities above the luminescence detection limit had normal levels of
      luminescence per bacterial cell in squid light organs, indicating that GacA is
      not required for light production within the host. The gacA mutants were impaired
      at competitive colonization and could only successfully cocolonize squid light
      organs when present in the seawater at higher inoculum densities than wild-type
      bacteria. Although severely impaired during colonization initiation, gacA mutants
      were not displaced by the wild-type strain in light organs that were colonized
      with both strains. This study establishes the role of GacA as a regulator of a
      beneficial animal-microbe association and indicates that GacA regulates
      utilization of growth substrates as well as other colonization traits.

PMID- 14645282
TI  - The Klebsiella pneumoniae wabG gene: role in biosynthesis of the core
      lipopolysaccharide and virulence.
AB  - To determine the function of the wabG gene in the biosynthesis of the core
      lipopolysaccharide (LPS) of Klebsiella pneumoniae, we constructed wabG nonpolar
      mutants. Data obtained from the comparative chemical and structural analysis of
      LPS samples obtained from the wild type, the mutant strain, and the complemented
      mutant demonstrated that the wabG gene is involved in attachment to alpha-L
      glycero-D-manno-heptopyranose II (L,D-HeppII) at the O-3 position of an alpha-D
      galactopyranosyluronic acid (alpha-D-GalAp) residue. K. pneumoniae nonpolar wabG
      mutants were devoid of the cell-attached capsular polysaccharide but were still
      able to produce capsular polysaccharide. Similar results were obtained with K.
      pneumoniae nonpolar waaC and waaF mutants, which produce shorter LPS core
      molecules than do wabG mutants. Other outer core K. pneumoniae nonpolar mutants
      in the waa gene cluster were encapsulated. K. pneumoniae waaC, waaF, and wabG
      mutants were avirulent when tested in different animal models. Furthermore, these
      mutants were more sensitive to some hydrophobic compounds than the wild-type
      strains. All these characteristics were rescued by reintroduction of the waaC,
      waaF, and wabG genes from K. pneumoniae.

PMID- 14645283
TI  - Transcription of quorum-sensing system genes in clinical and environmental
      isolates of Pseudomonas aeruginosa.
AB  - Quorum sensing (QS)-based transcriptional responses in Pseudomonas aeruginosa
      have been defined on the basis of increases in transcript levels of QS-controlled
      genes such as lasB and aprA following the hierarchical transcriptional increases
      of central controllers such as the lasR gene. These increases occur at high
      bacterial concentrations such as early-stationary-phase growth in vitro. However,
      the extent to which the increases occur in a variety of clinical and
      environmental isolates has not been determined nor is there extensive information
      on allelic variation in lasR genes. An analysis of the sequences of the lasR gene
      among 66 clinical and environmental isolates showed that 81% have a sequence
      either identical to that of strain PAO1 or with a silent mutation, 15% have
      nucleotide changes resulting in amino acid changes, and 5% have an insertion
      sequence in the lasR gene. Using real-time PCR to quantify transcript levels of
      lasR, lasB, and aprA in the early log and early stationary phases among 35
      isolates from bacteremia and pneumonia cases and the environment, we found most
      (33 of 35) strains had increases in lasR transcripts in early stationary phase
      but with a very wide range of final transcript levels per cell. There was a
      strong correlation (r(2) = 0.84) between early-log- and early-stationary-phase
      transcript levels in all strains, but this finding remained true only for the 50%
      of strains above the median level of lasR found in early log phase. There were
      significant (P < 0.05) but weak-to-modest correlations of lasR transcript levels
      with aprA (r(2) = 0.2) and lasB (r(2) = 0.5) transcript levels, but again this
      correlation occurred only in the 50% of P. aeruginosa strains with the highest
      levels of lasR transcripts in early stationary phase. There were no differences
      in distribution of lasR alleles among the bacteremia, pneumonia, or environmental
      isolates. Overall, only about 50% of P. aeruginosa strains from clinical and
      environmental sources show a lasR-dependent increase in the transcription of aprA
      and lasB genes, indicating that for about 50% of clinical isolates this
      regulatory system may not play a significant role in pathogenesis.

PMID- 14645284
TI  - Novel type of specialized transduction for CTX phi or its satellite phage RS1
      mediated by filamentous phage VGJ phi in Vibrio cholerae.
AB  - The main virulence factor of Vibrio cholerae, the cholera toxin, is encoded by
      the ctxAB operon, which is contained in the genome of the lysogenic filamentous
      phage CTX phi. This phage transmits ctxAB genes between V. cholerae bacterial
      populations that express toxin-coregulated pilus (TCP), the CTX phi receptor. In
      investigating new forms of ctxAB transmission, we found that V. cholerae
      filamentous phage VGJ phi, which uses the mannose-sensitive hemagglutinin (MSHA)
      pilus as a receptor, transmits CTX phi or its satellite phage RS1 by an efficient
      and highly specific TCP-independent mechanism. This is a novel type of
      specialized transduction consisting in the site-specific cointegration of VGJ phi
      and CTX phi (or RS1) replicative forms to produce a single hybrid molecule, which
      generates a single-stranded DNA hybrid genome that is packaged into hybrid viral
      particles designated HybP phi (for the VGJ phi/CTX phi hybrid) and HybRS phi (for
      the VGJ phi/RS1 hybrid). The hybrid phages replicate by using the VGJ phi
      replicating functions and use the VGJ phi capsid, retaining the ability to infect
      via MSHA. The hybrid phages infect most tested strains more efficiently than CTX
      phi, even under in vitro optimal conditions for TCP expression. Infection and
      lysogenization with HybP phi revert the V. cholerae live attenuated vaccine
      strain 1333 to virulence. Our results reinforce that TCP is not indispensable for
      the acquisition of CTX phi. Thus, we discuss an alternative to the current
      accepted evolutionary model for the emergence of new toxigenic strains of V.
      cholerae and the importance of our findings for the development of an
      environmentally safer live attenuated cholera vaccine.

PMID- 14645285
TI  - Horizontal transfer of segments of the 16S rRNA genes between species of the
      Streptococcus anginosus group.
AB  - The nature in variation of the 16S rRNA gene of members of the Streptococcus
      anginosus group was investigated by hybridization and DNA sequencing. A
      collection of 708 strains was analyzed by reverse line blot hybridization. This
      revealed the presence of distinct reaction patterns representing 11 different
      hybridization groups. The 16S rRNA genes of two strains of each hybridization
      group were sequenced to near-completion, and the sequence data confirmed the
      reverse line blot hybridization results. Closer inspection of the sequences
      revealed mosaic-like structures, strongly suggesting horizontal transfer of
      segments of the 16S rRNA gene between different species belonging to the
      Streptococcus anginosus group. Southern blot hybridization further showed that
      within a single strain all copies of the 16S rRNA gene had the same composition,
      indicating that the apparent mosaic structures were not PCR-induced artifacts.
      These findings indicate that the highly conserved rRNA genes are also subject to
      recombination and that these events may be fixed in the population. Such
      recombination may lead to the construction of incorrect phylogenetic trees based
      on the 16S rRNA genes.

PMID- 14645286
TI  - Role of narK2X and narGHJI in hypoxic upregulation of nitrate reduction by
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis is one of the strongest reducers of nitrate in the
      genus Mycobacterium: Under microaerobic conditions, whole cells exhibit
      upregulation of activity, producing approximately eightfold more nitrite than
      those of aerobic cultures of the same age. Assays of cell extracts from aerobic
      cultures and hypoxic cultures yielded comparable nitrate reductase activities.
      Mycobacterium bovis produced only low levels of nitrite, and this activity was
      not induced by hypoxia. M. tuberculosis has two sets of genes, narGHJI and narX
      of the narK2X operon, that exhibit some degree of homology to prokaryotic
      dissimilatory nitrate reductases. Each of these were knocked out by insertional
      inactivation. The narG mutant showed no nitrate reductase activity in whole
      culture or in cell-free assays, while the narX mutant showed wild-type levels in
      both assays. A knockout of the putative nitrite transporter narK2 gene produced a
      strain that had aerobic levels of nitrate reductase activity but failed to show
      hypoxic upregulation. Insertion of the M. tuberculosis narGHJI into a nitrate
      reductase Escherichia coli mutant allowed anaerobic growth in the presence of
      nitrate. Under aerobic and hypoxic conditions, transcription of narGHJI was
      constitutive, while the narK2X operon was induced under hypoxia, as measured with
      a lacZ reporter system and by quantitative real-time reverse PCR. This indicates
      that nitrate reductase activity in M. tuberculosis is due to the narGHJI locus
      with no detectable contribution from narX and that the hypoxic upregulation of
      activity is associated with the induction of the nitrate and nitrite transport
      gene narK2.

PMID- 14645287
TI  - Pathways leading from BarA/SirA to motility and virulence gene expression in
      Salmonella.
AB  - The barA and sirA genes of Salmonella enterica serovar Typhimurium encode a two
      component sensor kinase and a response regulator, respectively. This system
      increases the expression of virulence genes and decreases the expression of
      motility genes. In this study, we examined the pathways by which SirA affects
      these genes. We found that the master regulator of flagellar genes, flhDC, had a
      positive regulatory effect on the primary regulator of intestinal virulence
      determinants, hilA, but that hilA had no effect on flhDC. SirA was able to
      repress flhDC in a hilA mutant and activate hilA in an flhDC mutant. Therefore,
      although the flhDC and hilA regulatory cascades interact, sirA affects each of
      them independently. A form of BarA lacking the two N-terminal membrane-spanning
      domains, BarA198, autophosphorylates in the presence of ATP and transfers the
      phosphate to purified SirA. Phosphorylated SirA was found to directly bind the
      hilA and hilC promoters in gel mobility shift assays but not the flhD, fliA,
      hilD, and invF promoters. Given that the CsrA/csrB system is known to directly
      affect flagellar gene expression, we tested the hypothesis that SirA affects
      flagellar gene expression indirectly by regulating csrA or csrB. The sirA gene
      did not regulate csrA but did activate csrB expression. Consistent with these
      results, phosphorylated SirA was found to directly bind the csrB promoter but not
      the csrA promoter. We propose a model in which SirA directly activates virulence
      expression via hilA and hilC while repressing the flagellar regulon indirectly
      via csrB.

PMID- 14645288
TI  - Legume symbiotic nitrogen fixation by beta-proteobacteria is widespread in
      nature.
AB  - Following the initial discovery of two legume-nodulating Burkholderia strains (L.
      Moulin, A. Munive, B. Dreyfus, and C. Boivin-Masson, Nature 411:948-950, 2001),
      we identified as nitrogen-fixing legume symbionts at least 50 different strains
      of Burkholderia caribensis and Ralstonia taiwanensis, all belonging to the beta
      subclass of proteobacteria, thus extending the phylogenetic diversity of the
      rhizobia. R. taiwanensis was found to represent 93% of the Mimosa isolates in
      Taiwan, indicating that beta-proteobacteria can be the specific symbionts of a
      legume. The nod genes of rhizobial beta-proteobacteria (beta-rhizobia) are very
      similar to those of rhizobia from the alpha-subclass (alpha-rhizobia), strongly
      supporting the hypothesis of the unique origin of common nod genes. The beta
      rhizobial nod genes are located on a 0.5-Mb plasmid, together with the nifH gene,
      in R. taiwanensis and Burkholderia phymatum. Phylogenetic analysis of available
      nodA gene sequences clustered beta-rhizobial sequences in two nodA lineages
      intertwined with alpha-rhizobial sequences. On the other hand, the beta-rhizobia
      were grouped with free-living nitrogen-fixing beta-proteobacteria on the basis of
      the nifH phylogenetic tree. These findings suggest that beta-rhizobia evolved
      from diazotrophs through multiple lateral nod gene transfers.

PMID- 14645289
TI  - The Streptomyces coelicolor polynucleotide phosphorylase homologue, and not the
      putative poly(A) polymerase, can polyadenylate RNA.
AB  - A protein containing a nucleotidyltransferase motif characteristic of poly(A)
      polymerases has been proposed to polyadenylate RNA in Streptomyces coelicolor (P.
      Bralley and G. H. Jones, Mol. Microbiol. 40:1155-1164, 2001). We show that this
      protein lacks poly(A) polymerase activity and is instead a tRNA
      nucleotidyltransferase that repairs CCA ends of tRNAs. In contrast, a
      Streptomyces coelicolor polynucleotide phosphorylase homologue that exhibits
      polyadenylation activity may account for the poly(A) tails found in this
      organism.

PMID- 14645290
TI  - InvB is a type III secretion-associated chaperone for the Salmonella enterica
      effector protein SopE.
AB  - SopE is a bacteriophage-encoded effector protein of Salmonella enterica serovar
      Typhimurium that is translocated into the cytosol of eukaryotic cells by a type
      III secretion system (TTSS) (W.-D. Hardt, H. Urlaub, and J. E. Galan, Proc. Natl.
      Acad. Sci. USA 95:2574-2579, 1998; M. W. Wood, R. Rosqvist, P. B. Mullan, M. H.
      Edwards, and E. E. Galyov, Mol. Microbiol. 22:327-338, 1996). In this study, we
      provide evidence that an unlinked gene carried within the Salmonella
      pathogenicity island 1 (SPI-1), invB (K. Eichelberg, C. Ginocchio, and J. E.
      Galan, J. Bacteriol. 176:4501-4510, 1994), is required for the secretion of SopE
      through the SPI-1 TTSS. Furthermore, far-Western blotting analysis shows that
      SopE directly interacts with InvB through a domain located at its amino terminus.
      We conclude that InvB is the TTSS-associated chaperone for SopE.

PMID- 14645291
TI  - Differences in genetic and transcriptional organization of the glpTQ operons
      between Haemophilus influenzae type b and nontypeable strains.
AB  - The glpTQ operon of Haemophilus influenzae type b (Hib) and nontypeable H.
      influenzae (NTHi) strains is highly conserved, except for a 1.4-kb glpTQ
      intergenic region that was found in most Hib strains. The presence of this
      intergenic region results in divergent glpTQ transcriptional profiles for Hib and
      NTHi where Hib strains appear to have evolved an alternative promoter for glpQ
      expression. Based on the intergenic region's low G+C content, we speculate that
      this DNA fragment was acquired by lateral transfer.

PMID- 14645292
TI  - Colonial differentiation in Streptomyces coelicolor depends on translation of a
      specific codon within the adpA gene.
AB  - We identified adpA as an araC-like regulatory gene needed for colonial
      morphogenesis in Streptomyces coelicolor and showed that its activity depended on
      a unique TTA triplet corresponding to the leucyl-tRNA gene (bldA). These findings
      partially explained the dependence of aerial mycelium formation on a rare tRNA
      that is postulated to have developmental control functions.

PMID- 14645293
TI  - Control of Pseudomonas aeruginosa algZ expression by the alternative sigma factor
      AlgT.
AB  - AlgZ controls Pseudomonas aeruginosa alginate synthesis by activating algD, yet
      algZ expression is not detectable in nonmucoid strains. Mobility shift and
      Western blot assays revealed that algZ expression requires the sigma factor AlgT.
      The mapped algZ transcription start site revealed a consensus AlgT-dependent
      promoter that, when mutated, substantially reduced algZ transcription.

PMID- 14645294
TI  - Nora Volkow, MD: NIDA's new leader: from rejection to direction.

PMID- 14645295
TI  - Scientists never dreamed finding would shape a half-century of sleep research.

PMID- 14645303
TI  - Ethical aspects of recommending lifestyle interventions to patients.

PMID- 14645304
TI  - The 1997 Balanced Budget Act and home services among medicare patients.

PMID- 14645305
TI  - SARS infection among health care workers in Beijing, China.

PMID- 14645306
TI  - Temporal patterns of hepatic dysfunction and disease severity in patients with
      SARS.

PMID- 14645307
TI  - Inhibition of SARS-associated coronavirus infection and replication by RNA
      interference.

PMID- 14645308
TI  - Effect of magnesium sulfate given for neuroprotection before preterm birth: a
      randomized controlled trial.
AB  - CONTEXT: Prenatal magnesium sulfate may reduce the risk of cerebral palsy or
      death in very preterm infants. OBJECTIVE: To determine the effectiveness of
      magnesium sulfate given for neuroprotection to women at risk of preterm birth
      before 30 weeks' gestation in preventing pediatric mortality and cerebral palsy.
      DESIGN, SETTING, AND PATIENTS: Randomized controlled trial at 16 tertiary
      hospitals in Australia and New Zealand with stratification by center and multiple
      pregnancy. A total of 1062 women with fetuses younger than 30 weeks' gestation
      for whom birth was planned or expected within 24 hours were enrolled from
      February 1996 to September 2000 with follow-up of surviving children at a
      corrected age of 2 years. INTERVENTIONS: Women were randomly assigned to receive
      a loading infusion of 8 mL (4 g [16 mmol] of 0.5 g/mL of magnesium sulfate
      solution or isotonic sodium chloride solution [0.9%]) for 20 minutes followed by
      a maintenance infusion of 2 mL/h for up to 24 hours. MAIN OUTCOME MEASURES: Rates
      of total pediatric mortality, cerebral palsy, and the combined outcome of death
      or cerebral palsy at a corrected age of 2 years. RESULTS: Data were analyzed for
      1047 (99%) 2-year survivors. Total pediatric mortality (13.8% vs 17.1%; relative
      risk [RR], 0.83; 95% confidence interval [CI], 0.64-1.09), cerebral palsy in
      survivors (6.8% vs 8.2%; RR, 0.83; 95% CI, 0.54-1.27), and combined death or
      cerebral palsy (19.8% vs 24.0%; RR, 0.83; 95% CI, 0.66-1.03) were less frequent
      for infants exposed to magnesium sulfate, but none of the differences were
      statistically significant. Substantial gross motor dysfunction (3.4% vs 6.6%; RR,
      0.51; 95% CI, 0.29-0.91) and combined death or substantial gross motor
      dysfunction (17.0% vs 22.7%; RR, 0.75; 95% CI, 0.59-0.96) were significantly
      reduced in the magnesium group. CONCLUSIONS: Magnesium sulfate given to women
      immediately before very preterm birth may improve important pediatric outcomes.
      No serious harmful effects were seen.

PMID- 14645309
TI  - Chorioamnionitis and cerebral palsy in term and near-term infants.
AB  - CONTEXT: Half of all cases of cerebral palsy (CP) occur in term infants, for whom
      risk factors have not been clearly defined. Recent studies suggest a possible
      role of chorioamnionitis. OBJECTIVE: To determine whether clinical
      chorioamnionitis increases the risk of CP in term and near-term infants. DESIGN,
      SETTING, AND PATIENTS: Case-control study nested within a cohort of 231 582
      singleton infants born at 36 or more weeks' gestation between January 1, 1991,
      and December 31, 1998, in the Kaiser Permanente Medical Care Program, a managed
      care organization providing care for more than 3 million residents of northern
      California. Case patients were identified from electronic records and confirmed
      by chart review by a child neurologist, and comprised all children with moderate
      to severe spastic or dyskinetic CP not due to postnatal brain injury or
      developmental abnormalities (n = 109). Controls (n = 218) were randomly selected
      from the study population. MAIN OUTCOME MEASURE: Association between clinical
      chorioamnionitis and increased risk of CP in term and near-term infants. RESULTS:
      Most CP cases had hemiparesis (40%) or quadriparesis (38%); 87% had been
      diagnosed by a neurologist and 83% had undergone neuroimaging. Chorioamnionitis,
      considered present if a treating physician made a diagnosis of chorioamnionitis
      or endometritis clinically, was noted in 14% of cases and 4% of controls (odds
      ratio [OR], 3.8; 95% confidence interval [CI], 1.5-10.1; P =.001). Independent
      risk factors identified in multiple logistic regression included chorioamnionitis
      (OR, 4.1; 95% CI, 1.6-10.1), intrauterine growth restriction (OR, 4.0; 95% CI,
      1.3-12.0), maternal black ethnicity (OR, 3.6; 95% CI, 1.4-9.3), maternal age
      older than 25 years (OR, 2.6; 95% CI, 1.3-5.2), and nulliparity (OR, 1.8; 95% CI,
      1.0-3.0). The population-attributable fraction of chorioamnionitis for CP is 11%.
      CONCLUSION: Our data suggest that chorioamnionitis is an independent risk factor
      for CP among term and near-term infants.

PMID- 14645310
TI  - Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do
      randomized trials translate into clinical practice?
AB  - CONTEXT: Warfarin has been shown to be highly efficacious for preventing
      thromboembolism in atrial fibrillation in randomized trials, but its
      effectiveness and safety in clinical practice is less clear. OBJECTIVE: To
      evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death
      in atrial fibrillation within a usual care setting. DESIGN: Cohort study
      assembled between July 1, 1996, and December 31, 1997, and followed up through
      August 31, 1999. SETTING: Large integrated health care system in Northern
      California. PATIENTS: Of 13,559 adults with nonvalvular atrial fibrillation,
      11,526 were studied, 43% of whom were women, mean age 71 years, with no known
      contraindications to anticoagulation at baseline. MAIN OUTCOMES: Ischemic stroke,
      peripheral embolism, hemorrhage, and death according to warfarin use and
      comorbidity status, as determined by automated databases, review of medical
      records, and state mortality files. RESULTS: Among 11,526 patients, 397 incident
      thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred
      during 25,341 person-years of follow-up, and warfarin therapy was associated with
      a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism
      compared with no warfarin therapy (either no antithrombotic therapy or aspirin)
      after adjusting for potential confounders and likelihood of receiving warfarin.
      Warfarin was effective in reducing thromboembolic risk in the presence or absence
      of risk factors for stroke. A nested case-control analysis estimated a 64%
      reduction in odds of thromboembolism with warfarin compared with no
      antithrombotic therapy. Warfarin was also associated with a reduced risk of all
      cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial
      hemorrhage was uncommon, but the rate was moderately higher among those taking vs
      those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P
      =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy
      was not associated with an increased adjusted risk of nonintracranial major
      hemorrhage. The effects of warfarin were similar when patients with
      contraindications at baseline were analyzed separately or combined with those
      without contraindications (total cohort of 13,559). CONCLUSIONS: Warfarin is very
      effective for preventing ischemic stroke in patients with atrial fibrillation in
      clinical practice while the absolute increase in the risk of intracranial
      hemorrhage is small. Results of randomized trials of anticoagulation translate
      well into clinical care for patients with atrial fibrillation.

PMID- 14645311
TI  - Effectiveness and cost of olanzapine and haloperidol in the treatment of
      schizophrenia: a randomized controlled trial.
AB  - CONTEXT: Although olanzapine has been widely adopted as a treatment of choice for
      schizophrenia, its long-term effectiveness and costs have not been evaluated in a
      controlled trial in comparison with a standard antipsychotic drug. OBJECTIVE: To
      evaluate the effectiveness and cost impact of olanzapine compared with
      haloperidol in the treatment of schizophrenia. DESIGN AND SETTING: Double-blind,
      randomized controlled trial with randomization conducted between June 1998 and
      June 2000 at 17 US Department of Veterans Affairs medical centers. PARTICIPANTS:
      Three hundred nine patients with a Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder,
      serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine
      percent fully completed and 36% partially completed follow-up assessments.
      INTERVENTIONS: Patients were randomly assigned to receive flexibly dosed
      olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159);
      or haloperidol, 5 to 20 mg/d (n = 150), for 12 months. MAIN OUTCOME MEASURES:
      Standardized measures of symptoms, quality of life, neurocognitive status, and
      adverse effects of medication. Veterans Affairs administrative data and
      interviews concerning non-VA service use were used to estimate costs from the
      perspective of the VA health care system and society as a whole (ie, consumption
      of all resources on behalf of these patients). RESULTS: There were no significant
      differences between groups in study retention; positive, negative, or total
      symptoms of schizophrenia; quality of life; or extrapyramidal symptoms.
      Olanzapine was associated with reduced akathisia in the intention-to-treat
      analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary
      analysis including only observations during blinded treatment with study drug.
      Small but significant advantages were also observed on measures of memory and
      motor function. Olanzapine was also associated with more frequent reports of
      weight gain and significantly greater VA costs, ranging from 3000 dollars to 9000
      dollars annually. Differences in societal costs were somewhat smaller and were
      not significant. CONCLUSION: Olanzapine does not demonstrate advantages compared
      with haloperidol (in combination with prophylactic benztropine) in compliance,
      symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits
      in reducing akathisia and improving cognition must be balanced with the problems
      of weight gain and higher cost.

PMID- 14645312
TI  - Regionalization of high-risk surgery and implications for patient travel times.
AB  - CONTEXT: Given the strong volume-outcome relationships observed with many
      surgical procedures, restricting some procedures to hospitals exceeding a minimum
      volume standard is advocated. However, such regionalization policies might cause
      unreasonable travel burdens for surgical patients. OBJECTIVE: To estimate how
      minimum volume standards for esophagectomy and pancreatic resection would affect
      how long patients must travel for these procedures. DESIGN, SETTING, AND
      PATIENTS: Simulated trial based on Medicare claims and US road network data. All
      US hospitals in the 48 continental states were in the study if their surgical
      procedures included esophagectomy and pancreatic resection. Data from Medicare
      patients (N = 15,796) undergoing these 2 procedures for cancer between 1994 and
      1999 were used. MAIN OUTCOME MEASURE: Additional travel time for patients
      required to change to higher-volume centers as a result of alternative hospital
      volume standards (procedures per year). RESULTS: With low-volume standards
      (1/year for pancreatectomy; 2/year for esophagectomy), approximately 15% of
      patients would change to higher-volume centers, with negligible effect on their
      travel times. Most patients would need to travel less than 30 additional minutes
      (74% pancreatectomy; 76% esophagectomy). Many patients already lived closer to a
      higher-volume hospital (25% pancreatectomy; 26% esophagectomy). Conversely, with
      very high-volume standards (>16/year for pancreatectomy; >19/year for
      esophagectomy), approximately 80% of patients would change to higher-volume
      centers. More than 50% of these patients would increase their travel time by more
      than 60 minutes. Travel times would increase most for patients living in rural
      areas. CONCLUSIONS: Many patients travel past a higher-volume center to undergo
      surgery at a low-volume hospital. If not set too high, hospital volume standards
      could be implemented for selected operations without imposing unreasonable travel
      burdens on patients.

PMID- 14645313
TI  - An outbreak of Escherichia coli O157 infection following exposure to a
      contaminated building.
AB  - CONTEXT: Infection with Escherichia coli O157 causes an estimated 70 000
      diarrheal illnesses per year in the United States and can result in hemolytic
      uremic syndrome and death. Environmental contamination with E coli O157 may be a
      public health problem. OBJECTIVES: To determine risk factors for E coli O157
      infection during an outbreak investigation at a county fair and to evaluate
      environmental contamination as a possible cause of the outbreak. DESIGN, SETTING,
      AND PARTICIPANTS: Case-control study of 23 patients (median age, 15 years) and 53
      age-matched controls who had attended the Lorain County, Ohio, fair between
      August 20 and August 26, 2001. Case-patients had laboratory-confirmed E coli O157
      infection, hemolytic-uremic syndrome, or bloody diarrhea within 7 days of
      attending the fair; controls attended the fair and did not have diarrhea. MAIN
      OUTCOME MEASURES: Risk factors for infection and isolates of E coli O157 from
      environmental specimens. RESULTS: Six (26%) case-patients were hospitalized and 2
      (9%) developed hemolytic-uremic syndrome. Case-patients were more likely than
      controls to have visited building A (a multipurpose community facility on the
      fairgrounds; matched odds ratio [MOR], 21.4 [95% confidence interval [CI], 2.7
      170.7]). Among visitors to building A, illness was independently associated with
      attending a dance in the building (MOR, 7.5; 95% CI, 1.4-41.2), handling sawdust
      from the floor (MOR, 4.6; 95% CI, 1.1-20.0), or eating and/or drinking in the
      building (MOR, 4.5; 95% CI, 1.2-16.6). Twenty-four (44%) of 54 specimens
      collected from building A 6 weeks after the fair grew Shiga toxin-producing E
      coli O157. Isolates from sawdust, the rafters, and other surfaces were identical
      by molecular fingerprinting to patient isolates. Sawdust specimens collected 42
      weeks after the fair also grew the same E coli O157 strain. CONCLUSIONS: Absence
      of evidence implicating specific food or beverage sources and the recovery of E
      coli O157 from the rafters suggest that airborne dispersion of bacteria
      contributed to the contamination. Because E coli O157 can survive in the
      environment for more than 10 months, humans may be at risk of infection long
      after an environment is initially contaminated.

PMID- 14645314
TI  - Early use of the pulmonary artery catheter and outcomes in patients with shock
      and acute respiratory distress syndrome: a randomized controlled trial.
AB  - CONTEXT: Many physicians believe that the pulmonary artery catheter (PAC) is
      useful for the diagnosis and treatment of cardiopulmonary disturbances; however,
      observational studies suggest that its use may be harmful. OBJECTIVE: To
      determine the effects on outcome of the early use of a PAC in patients with shock
      mainly of septic origin, acute respiratory distress syndrome (ARDS), or both.
      DESIGN, SETTING, AND PATIENTS: A multicenter randomized controlled study of 676
      patients aged 18 years or older who fulfilled the standard criteria for shock,
      ARDS, or both conducted in 36 intensive care units in France from January 30,
      1999, to June 29, 2001. INTERVENTION: Patients were randomly assigned to either
      receive a PAC (n = 335) or not (n = 341). The treatment was left to the
      discretion of each individual physician. MAIN OUTCOME MEASURES: The primary end
      point was mortality at 28 days. The principal secondary end points were day 14
      and 90 mortality; day 14 organ system, renal support, and vasoactive agents-free
      days; hospital, intensive care unit, and mechanical ventilation-free days at day
      28. RESULTS: The 2 groups were similar at baseline. There were no significant
      differences in mortality with or without the PAC at day 14: 49.9% vs 51.3%
      (mortality relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P
      =.70); day 28: 59.4% vs 61.0% (RR, 0.97; 95% CI, 0.86-1.10; P =.67); or day 90:
      70.7% vs 72.0% (RR, 0.98; 95% CI, 0.89-1.08; P =.71). At day 14, the mean (SD)
      number of days free of organ system failures with or without the PAC (2.3 [3.6]
      vs 2.4 [3.5]), renal support (7.4 [6.0] vs 7.5 [5.9]), and vasoactive agents (3.8
      [4.8] vs 3.9 [4.9]) did not differ. At day 28, mean (SD) days in hospital with or
      without the PAC (0.9 [3.6] vs 0.9 [3.3]), in the intensive care unit (3.4 [6.8]
      vs 3.3 [6.9]), or mechanical ventilation use (5.2 [8.5] vs 5.0 [8.5]) did not
      differ. CONCLUSION: Clinical management involving the early use of a PAC in
      patients with shock, ARDS, or both did not significantly affect mortality and
      morbidity.

PMID- 14645315
TI  - A 62-year-old woman with chronic obstructive pulmonary disease.

PMID- 14645316
TI  - Hope for perinatal prevention of cerebral palsy.

PMID- 14645317
TI  - The arc of the pulmonary artery catheter.

PMID- 14645319
TI  - JAMA patient page. Cerebral palsy.

PMID- 14645320
TI  - Thymidine analogue mutations in antiretroviral-naive HIV-1 patients on triple
      therapy including either zidovudine or stavudine.
AB  - AIMS: The aims of this study were to: (i) determine the incidence of thymidine
      associated mutations (TAMs) in an observational clinical cohort of naive HIV-1
      patients who stopped first-line therapy including either zidovudine or stavudine;
      and (ii) assess the immunological and virological responses to subsequent second
      line therapy in patients who switched from zidovudine to stavudine or conversely.
      PATIENTS AND METHODS: Plasma samples from 165 patients who stopped first-line
      antiretroviral therapy containing either zidovudine or stavudine were examined
      for the presence of drug-resistant genotypes. Subsequent second-line
      immunological and virological follow-up was performed in 136 patients who
      switched from zidovudine to stavudine and conversely. RESULTS: Among the 93
      patients who stopped first-line therapy including zidovudine and the 72 who
      stopped first-line therapy including stavudine, genotypic resistance testing was
      available for 67 (72%) and 54 (75%), respectively. The presence of TAMs was
      significantly more frequent in the zidovudine than the stavudine group (23.8%
      versus 5.5; P = 0.006). The short- and long-term immunological and virological
      responses to second-line therapy were comparable in the zidovudine and stavudine
      groups, despite different baseline profiles of viral resistance (median increase
      in CD4 cells/mm3 at 1 year of therapy, 118 versus 119; viral load <400 copies/mL,
      47% versus 47%). CONCLUSIONS: These results suggest that TAMs occur in more
      patients on antiretroviral regimens including zidovudine than on regimens
      including stavudine. Although the results from observational studies should be
      interpreted cautiously, these findings may be useful in determining the optimal
      sequencing of zidovudine and stavudine for the treatment of naive HIV-1-infected
      patients.

PMID- 14645321
TI  - Molecular analysis of florfenicol-resistant Escherichia coli isolates from pigs.
AB  - OBJECTIVES: The aim of this study was to analyse florfenicol-resistant
      Escherichia coli isolates from pigs for the genetic basis of florfenicol
      resistance, and to compare these data with those previously determined for E.
      coli isolates from cattle and poultry. METHODS: Fourteen porcine E. coli isolates
      were included in this study and subjected to serotyping, plasmid profiling and
      macrorestriction analysis. MICs of florfenicol were determined by broth
      microdilution. The presence of the gene floR was confirmed by hybridization and
      PCR analysis. Transformation experiments were conducted to isolate florfenicol
      resistance plasmids. The floR region of a florfenicol resistance plasmid was
      cloned and sequenced. RESULTS: All florfenicol-resistant E. coli isolates
      exhibited MICs of florfenicol >128 mg/L and carried the floR gene. A single
      isolate had a floR-carrying plasmid of approximately 35 kb, designated pMBSF1.
      Sequence analysis identified the floR gene flanked by truncated transposase
      genes. Moreover, a truncated copy of Tn5393 with complete streptomycin resistance
      genes strA and strB was found upstream of the floR gene of pMBSF1. Chromosomally
      resistant E. coli isolates, which shared the same BlnI macrorestriction pattern,
      differed in their floR hybridization patterns. CONCLUSION: The plasmid pMBSF1 is
      the smallest floR-carrying plasmid reported to date. Its floR region differed
      from those previously found in E. coli isolates from cattle. Variations in the
      RFLPs of chromosomal EcoRI fragments carrying floR in isolates that had the same
      macrorestriction pattern might suggest variable chromosomal integration sites.

PMID- 14645322
TI  - Relationships among various nucleoside resistance-conferring mutations in the
      reverse transcriptase of HIV-1.
AB  - Highly active antiretroviral therapy has significantly improved HIV-related
      morbidity and mortality, and nucleoside reverse transcriptase inhibitors remain
      an essential component of treatment. However, the emergence of HIV-1 mutated
      strains that are resistant to one or more antiretroviral drugs is a leading cause
      of treatment failure among patients living with HIV/AIDS. These resistant strains
      may often suffer from a replication disadvantage in comparison with wild-type
      viruses when grown in the absence of drug pressure and a potential benefit in
      this regard has been shown for lamivudine-resistant viruses that contain a M184V
      mutation in reverse transcriptase, as well as for several other drug-resistant
      viral variants. Interactions between different mutations may complicate the
      understanding of HIV drug resistance with regard to the likelihood of therapeutic
      success.

PMID- 14645323
TI  - Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients.
AB  - Highly active antiretroviral therapy (HAART) has had a significant impact on the
      natural history of human immunodeficiency virus (HIV) infection, leading to a
      remarkable decrease in its morbidity and mortality, but is frequently associated
      with clinical and metabolic complications. Fat redistribution or lipodystrophy,
      hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and diabetes
      mellitus have been extensively reported in subjects treated with protease
      inhibitor (PI)-based antiretroviral regimens. In particular, dyslipidaemia occurs
      in up to 70-80% of HIV-infected individuals receiving HAART and can be associated
      with all the available PIs, although hypertriglyceridaemia appears to be more
      frequent in patients treated with ritonavir, ritonavir-saquinavir, or ritonavir
      lopinavir. The potential long-term consequences of HAART-associated
      hyperlipidaemia are not completely understood, but an increased risk of premature
      coronary artery disease has been reported in young HIV-positive persons receiving
      PIs. Dietary changes, regular aerobic exercise and switching to a PI-sparing
      regimen may act favourably on dyslipidaemia. Lipid-lowering therapy is often
      required with statins or fibrates. The choice of hypolipidaemic drugs should take
      into account potential pharmacological interactions with antiretroviral agents.

PMID- 14645324
TI  - New agents active against Mycobacterium avium complex selected by molecular
      topology: a virtual screening method.
AB  - OBJECTIVES: In order to select new drugs and to predict their in vitro activity
      against Mycobacterium avium complex (MAC), new quantitative structure-activity
      relationship (QSAR) models were developed. METHODS: The activities against MAC of
      29 structurally heterogeneous drugs were examined by means of linear discriminant
      analysis (LDA) and multilinear regression analysis (MLRA) by using topological
      indices (TI) as structural descriptors. In vitro antimycobacterial activities
      were determined by a broth microdilution method with 7H9 medium. RESULTS: The
      topological model obtained successfully classifies over 80% of compounds as
      active or inactive; consequently, it was applied in the search for new molecules
      active against MAC. From among the selected candidates demonstrating in vitro
      activity, aflatoxin B1, benzalkonium chloride and pentamidine stand out, with
      MIC50s between 4 and 32 mg/L. CONCLUSION: The method described in this work is
      able to select molecules active against MAC.

PMID- 14645325
TI  - Predicting the therapeutic response in patients with chronic hepatitis C: the
      role of viral kinetic studies.
AB  - A substantial proportion of patients infected with hepatitis C virus (HCV)
      genotype 1 still does not respond to pegylated interferon-alfa/ribavirin
      (IFN/RBV) therapy. Factors which identify potential non-responders are needed to
      limit exposure to drugs in patients unlikely to benefit from treatment and to
      save health care resources. Host predictive factors have a low negative
      predictive value. In contrast, viral factors have a high precision in predicting
      outcome of therapy. Viral kinetics are the basis for the study of response of
      therapy. The decrease in viral load within 24 h after administration of a single
      test dose of conventional IFN reflects the IFN-sensitivity of the virus strain
      and predicts the outcome of conventional IFN/RBV therapy even before treatment
      with a specificity of 100% and a sensitivity of 83%. In contrast to conventional
      IFN, the two available PEG-IFN preparations differ considerably in how they
      suppress viral replication, and cut-off values have to be prospectively
      established separately for each drug. Patients without an early virological
      response (HCV-RNA either undetectable or decrease by >or=2 log10 after 12 weeks)
      (EVR), do not achieve a sustained virological response (SVR; negative predictive
      value: 97-98%). Thus, in the absence of an EVR, treatment should be stopped. The
      outcome of PEG-IFN alfa-2a/RBV combination therapy is dependent on the rapidity
      of the virological response. Patients who become HCV-RNA negative after 4 weeks
      have the best chance of achieving an SVR. The rapidity of viral elimination may
      be a useful guide to tailoring the length of treatment in patients with an EVR.

PMID- 14645326
TI  - One-year uptake of pneumococcal conjugate vaccine: a national survey of family
      physicians and pediatricians.
AB  - BACKGROUND: Pneumococcal conjugate vaccine (PCV7) was recommended by June 2000
      for administration to all US children </=23 months old and to children at high
      risk for pneumococcal disease 24 to 59 months old. We sought to identify
      physician characteristics associated with adoption of the recommendation within 1
      year. METHODS: We conducted a cross-sectional mail survey from April to July,
      2001, of 788 family physicians (FP) and 833 pediatricians (PD) in 24 states. We
      measured whether physicians had adopted PCV7 recommendations, their expectations
      of the effectiveness of PCV7, the number of vaccine injections they would
      consider administering at 1 visit, and barriers to administering multiple
      injections. RESULTS: Response rate was 60%. Overall, 87% of physicians had
      adopted PCV7 recommendations (68% FP; 99% PD; P <.001). FP adopters are
      significantly more likely than nonadopters to believe PCV7 will be effective in
      preventing pneumococcal sepsis and meningitis, as well as >25% of cases of otitis
      media. In multivariable logistic regression analyses of adoption of PCV7, FP who
      have higher proportions of African American patients and patients on Medicaid,
      see greater numbers of newborns, work in practices of >/=4 physicians, and are
      willing to consider administering at least 4 vaccine injections at 1 visit are
      significantly more likely to have adopted PCV7. Concerns about vaccine cost and
      reimbursement were the most commonly cited factors in physicians' decisions not
      to adopt PCV7 recommendations. CONCLUSIONS: One year after PCV7 was recommended,
      nearly all pediatricians and a majority of family physicians had incorporated
      this vaccine into their practices. Barriers to higher rates of uptake-especially
      among family physicians-must be addressed to achieve immunization goals with this
      new vaccine.

PMID- 14645327
TI  - The effectiveness of various postpartum depression treatments and the impact of
      antidepressant drugs on nursing infants.
AB  - BACKGROUND: Postpartum depression is seen in approximately 13% of women who have
      recently given birth; unfortunately, it often remains untreated. Important causes
      for undertreatment of this disorder are providers' and patients' lack of
      information about the effectiveness of various treatments, and their concerns
      about the impact of treatment on nursing infants. This article presents research
      based evidence on the benefits of various treatments for postpartum depression
      and their potential risks to nursing infants. METHODS: The medical literature on
      postpartum depression treatment was reviewed by searching MEDLINE and Current
      Contents using such key terms as "postpartum depression," "treatment," "therapy,"
      "psychotherapy," and "breastfeeding." RESULTS AND CONCLUSIONS: There is evidence
      that postpartum depression improves with antidepressant drug therapy, estrogen,
      individual psychotherapy, nurse home visits, and possibly group therapy. Of the
      more frequently studied antidepressant drugs in breastfeeding women, paroxetine,
      sertraline, and nortriptyline have not been found to have adverse effects on
      infants. Fluoxetine, however, should be avoided in breastfeeding women. By
      administering effective treatment to women with postpartum depression, we can
      positively impact the lives of mothers, their infants, and other family members.

PMID- 14645328
TI  - Managed care and primary physician satisfaction.
AB  - BACKGROUND: We examined whether physician compensation, financial incentives, and
      care management tools were associated with primary physician job and referral
      satisfaction. Our study was guided by a conceptual model of physician
      satisfaction derived from published evidence. METHODS: A cross-sectional survey
      was performed of 495 primary physicians (family practitioners, general
      practitioners, general internists) in the Seattle metropolitan area in 1997.
      RESULTS: Bivariate analyses revealed that salary compensation, productivity
      bonuses, and withholds for referrals were associated with job and referral
      dissatisfaction. However, after controlling for physician, practice, and office
      characteristics, only the association between salary payment and job
      dissatisfaction remained significant. Practice in offices with more physicians
      had the strongest association with physician job dissatisfaction. CONCLUSIONS:
      Although managed care features are correlated with physician job and referral
      dissatisfaction, the source of dissatisfaction may originate from being an
      employed physician in a large medical group with more physicians, which may be
      more likely to impose bureaucratic controls that limit physician autonomy.

PMID- 14645329
TI  - Assessing the cultures of medical group practices.
AB  - BACKGROUND: The culture of medical group practices is gaining increasing
      attention as one of the most important organizational factors influencing the
      costs and quality of health care. Based on organizational theory, we propose that
      the culture of the practice differs depending on size, ownership, location, and
      the number of medical specialties. METHODS: A survey was sent to 1223 physicians
      in 191 clinics in the upper Midwest. The clinic response rate was 77%. The survey
      instrument identifies 9 culture dimensions, each with 3 to 6 measurement
      statements. RESULTS: Smaller clinics had higher scores on 6 of the 9 dimensions.
      Physician-owned clinics had higher scores on 4 of the 9 dimensions, whereas
      system-owned clinics had a higher score on only 1 dimension. Only 1 dimension
      differed among the locations. Single-specialty clinics had higher scores on 4
      dimensions and multispecialty clinics had higher scores on 2 dimensions.
      CONCLUSION: Our data confirm the contention that the culture of medical group
      practices varies considerably; to a degree, this variance is as predicted by
      organizational theory. The culture changes as group practices become larger and
      more complex through diversification into multispecialty practices or become part
      of larger health care systems.

PMID- 14645330
TI  - The effect of exit-interview patient education on no-show rates at a family
      practice residency clinic.
AB  - BACKGROUND: Residency clinics with high no-show rates experience negative
      ramifications in patient health care, continuity, clinic productivity, and
      learning experiences for residents. This study tested patient education in the
      form of an exit interview to reduce no-show rates. METHODS: All eligible new
      patients at St. Mary's Family Practice Center between 1 February 1996 and 30
      April 1997 were offered study enrollment. Patients with initial appointments
      during 5 of 9 clinic sessions were offered an exit interview with visit
      debriefing, written patient information where appropriate, and review of clinic
      policies. Missed patients or those with initial appointments during the remaining
      4 sessions formed the control group. Interviewers were social work, medical, and
      nursing students. Insurance and subsequent appointment data were obtained from
      billing records. Median household income of ZIP codes in which patients resided
      was obtained from the 1990 Federal Census data. Data were analyzed using chi(2)
      tests, Wilcoxon rank-sum tests, and logistic regression. RESULTS: One hundred
      forty-six patients were enrolled into the intervention and 297 into the control
      group. Simple logistic regression showed a significant reduction in the risk of
      no-shows in the intervention group (odds ratio = 0.71, P =.04). CONCLUSIONS: The
      exit interview improved attendance at subsequent visits.

PMID- 14645331
TI  - Patient acceptance and the psychological effects of women experiencing
      telecolposcopy and colposcopy.
AB  - BACKGROUND: The purpose of the study was to assess patient acceptance and
      psychological effects in women experiencing telecolposcopy compared with
      colposcopy. METHODS: Convenience samples of 150 and 263 women scheduled for
      colposcopy or telecolposcopy, respectively, completed questionnaires assessing
      anxiety (Prime MD), depression [Center for Epidemiologic Studies/Depressed Mood
      Scale (CES-D)], health beliefs and concerns, coping style (Miller Behavioral
      Style Score) and examination acceptance and satisfaction. Test scores and subject
      responses were compared using the t test and Wilcoxon rank sum test. RESULTS:
      Mean scores representing mild anxiety (1.3 and 1.2, P =.7) and mild depression
      (35.4 and 36.3, P =.4) were reported for the telecolposcopy and colposcopy
      groups, respectively. The telecolposcopy group indicated significantly greater
      mean scores for the examination, saving them time and money compared with the
      colposcopy group. Women in both groups were highly satisfied with their
      examinations and care. CONCLUSIONS: In general, women reported very high levels
      of satisfaction with telecolposcopy and colposcopy. Potential savings of time and
      money and improved health care were considered of particular value to women
      examined by telecolposcopy. Telecolposcopy seems to be well accepted by rural
      women.

PMID- 14645332
TI  - The relationship between primary care, income inequality, and mortality in US
      States, 1980-1995.
AB  - OBJECTIVES: This study tests the robustness of the relationships between primary
      care, income inequality, and population health by (1) assessing the relationship
      during 4 time periods-1980, 1985, 1990 and 1995; (2) examining the independent
      effect of components of the primary care physician supply; (3) using 2 different
      measures of income inequality (Robin Hood index and Gini coefficient); and (4)
      testing the robustness of the association by using 5-year time-lagged independent
      variables. DATA SOURCES/STUDY SETTING: Data are derived from the Compressed
      Mortality Files, the US Department of Commerce and the Census Bureau, the
      National Center for Health Statistics, the Centers for Disease Control and
      Prevention, and the American Medical Association Physician Master File. The unit
      of analysis was the 50 US states over a 15-year period. STUDY DESIGN: Ecological,
      cross-sectional design for 4 selected years (1980, 1985, 1990, 1995), and
      incorporating 5-year time-lagged independent variables. The main outcome measure
      is age-standardized, all-cause mortality per 100,000 population in all 50 US
      states in all 4 time periods. DATA COLLECTION/EXTRACTION METHODS: The study used
      secondary data from publicly available data sets. The CDC WONDER/PC software was
      used to obtain mortality data and directly standardize them for age to the 1980
      US population. Data used to calculate the income inequality measure came from the
      US census population and housing summary tapes for the years 1980 to 1995. Counts
      of the number of households that fell into each income interval along with the
      total aggregate income and the median household income were obtained for each
      state. The Gini coefficient for each state was calculated using software
      developed for this purpose. RESULTS: In weighted multivariate regressions, both
      contemporaneous and time-lagged income inequality measures (Gini coefficient,
      Robin Hood Index) were significantly associated with all-cause mortality (P <.05
      for both measures for all time periods). Contemporaneous and time-lagged primary
      care physician-to-population ratios were significantly associated with lower all
      cause mortality (P <.05 for all 4 time periods), whereas specialty care measures
      were associated with higher mortality (P <.05 for all time periods, except 1990,
      where P <.1). Among primary care subspecialties, only family medicine was
      consistently associated with lower mortality (P <.01 for all time periods).
      CONCLUSIONS: Enhancing primary care, particularly family medicine, even in states
      with high levels of income inequality, could lead to lower all-cause mortality in
      those states.

PMID- 14645333
TI  - Managing Alzheimer dementia tomorrow.
AB  - BACKGROUND: Acetylcholinesterase inhibitors are the first drugs to alter the
      devastating effects of Alzheimer disease. The next generation of drugs will
      prevent the beta-amyloid plaques and neurofibrillary tangles or block enzymes
      that lead to neuron destruction. Effective use of these medications will require
      early identification of patients at risk. METHODS: Using the PubMed service of
      the National Library of Medicine, all English language articles published in
      2000, 2001 and the first half of 2002 with a key word of 'dementia' were reviewed
      for articles that described the emerging pathophysiologic model for Alzheimer
      disease. FINDINGS: Standardized clinical screening tools, such as the mini-mental
      status examination and the clock test, administered longitudinally and correlated
      with family observations, can identify many at-risk patients. Genetic testing can
      identify a known mutation in 70% of patients who have a high family incidence of
      Alzheimer disease but awaits effective prevention before being useful. The
      molecular mechanisms of Alzheimer disease will eventually lead to prevention.
      CONCLUSION: Today, these patients benefit from nutritional support and lifestyle
      enhancement encouraged through a continuous primary care relationship.

PMID- 14645334
TI  - Persistent knee pain in a recreational runner.

PMID- 14645335
TI  - The corporate transformation of medicine and its impact on costs and access to
      care.

PMID- 14645336
TI  - Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly
      patients.

PMID- 14645337
TI  - Levofloxacin-induced tendon rupture: a case report and review of the literature.

PMID- 14645338
TI  - Unrelenting pain.

PMID- 14645339
TI  - Preventing invasive pneumococcal disease in children.

PMID- 14645340
TI  - Maintenance of board certification.

PMID- 14645343
TI  - Basement membrane components.

PMID- 14645344
TI  - Best Practice No 174. Best practice guidelines for the examination of specimens
      for the diagnosis of parasitic infections in routine diagnostic laboratories.
AB  - Although most routine microbiology diagnostic laboratories process specimens for
      the diagnosis of parasitic infections, there are no best practice guidelines
      either for processing or for referral to specialist centres. Microscopy for
      parasites is most often requested on faecal samples, but urine, sputum, liver
      aspirates, duodenal aspirates, bile, corneal scrapings, contact lens fluid, and
      tissue are also encountered. Diagnosis of certain parasitic infections requires
      serology or polymerase chain reaction. These are undertaken in specialist
      laboratories, which should be consulted for expert advice on diagnosis and
      management of parasitic infections. Clinical Pathology Accreditation UK (CPA) has
      defined standards for assessing the quality of service provided by laboratories,
      but these do not include scientific and technical aspects. The Association of
      Medical Microbiologists has recently published Standards for laboratory practice
      in medical microbiology, which covers scientific and technical aspects, mainly
      bacteriological examination of specimens in routine diagnostic microbiology
      laboratories. These guidelines are complementary to the CPA standards and aim to
      ensure a consistent and high quality of service. This article provides best
      practice guidelines for the diagnosis of parasitic infections.

PMID- 14645345
TI  - Alpha-methylacyl CoA racemase (P504S): overview and potential uses in diagnostic
      pathology as applied to prostate needle biopsies.
AB  - The diagnosis of prostatic adenocarcinoma remains dependent on the recognition of
      basic haematoxylin and eosin criteria. The discovery of alpha-methylacyl CoA
      racemase/P504S (AMACR/P504S) overexpression in prostate cancer represents a
      triumph of high throughput microarray technology, and is a powerful demonstration
      of how this methodology can be used to facilitate the rapid development of
      diagnostically relevant antibodies. Immunohistochemistry with anti-AMACR/P504S is
      useful for detecting prostate cancer in the full range of prostate specimens
      encountered in surgical pathology, be they needle biopsies, transurethral
      resection of prostate chips, or prostatectomies. In particular, studies to date
      with AMACR/P504S clearly demonstrate the ability of this marker to support a
      diagnosis of malignancy in prostate needle biopsies. This is particularly true
      when it is combined with negative staining for a basal cell marker, such as
      34betaE12 or p63. Although it has limitations with respect to sensitivity and
      specificity, AMACR/P504S will no doubt become a standard adjunctive stain used by
      pathologists seeking to reach a definitive diagnosis in prostate biopsies
      considered to be atypical, but not diagnostic of malignancy on haematoxylin and
      eosin sections alone.

PMID- 14645346
TI  - Immunohistochemical analysis of adenocarcinoma of the small intestine: a tissue
      microarray study.
AB  - BACKGROUND: Primary adenocarcinomas of the small intestine are rare, and the
      genetic mechanisms involved in their carcinogenesis remain unclear. AIM: To
      examine the expression of candidate proteins in small intestinal adenocarcinomas
      by immunohistochemistry performed on tissue microarrays (TMAs). METHODS: Twenty
      seven primary sporadic small intestinal adenocarcinomas were analysed. The TMA
      technique was validated by comparing immunohistochemical labelling of hMLH1 and
      hMSH2 on TMAs and the tissue sections they derived from. The expression of Smad4,
      hMSH6, beta catenin, and p53 was investigated and results compared with those
      obtained in 14 malignant ampullary tumours. RESULTS: TMA technology with
      threefold redundancy adequately represented the immunohistochemical pattern of
      small intestinal adenocarcinomas. Loss of hMLH1 expression, but not hMSH2 or
      hMSH6, was seen in two of 27 small intestinal adenocarcinomas. All ampullary
      tumours showed nuclear staining for hMSH2 and hMSH6. One case showed lack of
      immunostaining for hMLH1. Smad4 expression was absent in five small intestinal
      adenocarcinomas and two ampullary tumours. Overexpression of p53 was detected in
      the nuclei of 14 of the 27 small intestinal adenocarcinomas, and five of the 14
      ampullary tumours. Nuclear or cytoplasmic expression of beta catenin was present
      in all specimens. CONCLUSION: Inactivation of the SMAD4/DPC4 gene seems to be
      involved in small intestinal adenocarcinoma tumorigenesis. Overexpression of p53
      and abnormal expression of beta catenin are two common events, unlike the loss of
      expression of the DNA mismatch repair proteins (hMLH1, hMSH2, and hMSH6). The
      carcinogenetic process appears to be similar in small intestinal adenocarcinomas
      and malignant ampullary tumours.

PMID- 14645347
TI  - SV40 Tag DNA sequences, present in a small proportion of human hepatocellular
      carcinomas, are associated with reduced survival.
AB  - AIMS: To study the association between simian virus 40 (SV40) and human
      hepatocarcinogenesis. METHODS: Polymerase chain reaction (PCR) to detect SV40
      large T antigen (Tag) DNA was performed on: 50 human hepatocellular carcinoma
      (HCCs) diagnosed between 1978 and 1989 (cohort A); 20 cases of alcoholic liver
      cirrhosis from the same period; and 20 HCCs diagnosed after 1997 (cohort B). PCR
      to detect SV40 regulatory sequence and SV40 Tag immunohistochemistry were
      performed on selected cases from cohorts A and B. Amplified products were
      directly sequenced. Immunohistochemistry for p53 and pRb and clinicopathological
      analyses were performed on selected cases from cohorts A and B. Complete survival
      data were collected for cohort A. RESULT: SV40 Tag DNA was found in five cohort A
      HCCs but not in alcoholic liver cirrhosis cases or cohort B HCCs. Neither SV40
      regulatory sequence nor SV40 Tag protein were demonstrated in Tag DNA positive
      HCCs. No clinicopathological differences existed between Tag DNA positive and
      negative HCCs, but the presence of Tag DNA was associated with reduced disease
      specific survival. Relatively fewer Tag DNA positive than negative HCCs expressed
      p53, but loss of pRb expression was similar in the two groups. Patients with Tag
      DNA positive HCCs were unlikely to have received SV40 contaminated poliovirus
      vaccine. CONCLUSIONS: SV40 Tag DNA is present in a small proportion of historical
      HCCs and may contribute to their pathogenesis and influence their outcome. The
      source of the virus is uncertain and more recent HCCs show no evidence of SV40.

PMID- 14645348
TI  - Detection of human papillomavirus DNA in oral inverted ductal papillomas.
AB  - AIMS: To determine the presence or absence of human papillomavirus (HPV) DNA in
      oral inverted ductal papillomas (IDPs) using in situ hybridisation (ISH), and to
      analyse all cases for histological features of HPV infection. METHODS: Six cases
      were retrieved from archival material and paraffin wax blocks were submitted for
      the detection of HPV DNA by means of ISH. A wide spectrum probe for HPV subtypes
      6, 11, 16, 18, 31, 33, 45, 51, and 52 was used initially. Cases that were
      positive using this wide spectrum probe were further subtyped using HPV type
      specific probes (6/11, 16/18, and 31/33). The histological features of all
      tumours were analysed using routine microscopy. RESULTS: Of the six cases of oral
      IDP identified, three were positive for HPV subtypes 6/11. All positive cases
      showed histological features of HPV infection (koilocytosis, papillomatosis,
      binucleated keratinocytes, and abnormal mitosis) in both the surface and the
      inverted epithelium. The three cases that tested negative for HPV DNA also
      exhibited focal histological features of HPV infection (two in the surface
      epithelium and one in the endophytic epithelium). CONCLUSIONS: These are the
      first documented cases of oral IDP to demonstrate positivity for HPV DNA and also
      to show histological features of HPV infection.

PMID- 14645349
TI  - Salivary duct carcinoma: immunohistochemical profile of an aggressive salivary
      gland tumour.
AB  - BACKGROUND: Salivary duct carcinoma (SDC) is considered to be a distinct
      malignancy of the major salivary glands, because of its highly aggressive
      behaviour, and the high rate of recurrence, metastasis, and disease related
      death. AIMS: To investigate expression of the proteins involved in the
      retinoblastoma (pRb) and p53 pathways, which control cell cycle progression at
      the G1/S checkpoint, and also expression of the c-erbB-2 oncoprotein in SDCs.
      METHODS: Using a streptavidin-biotin method, five cases of SDC were evaluated
      immunohistochemically for the presence of cyclin D1, CDK4 (cyclin dependent
      kinase 4), p16 (CDK2A), pRb (retinoblastoma protein), E2F-1, p53, mdm2 (murine
      double minute 2), bcl-2, and the c-erbB-2 oncoprotein to determine whether there
      was a correlation between the expression of these proteins and patient outcome.
      RESULTS: All of the cases showed deregulation of the pRb and p53 pathways. Of the
      five patients analysed, only the patient with longterm survival (10 years) was
      not positive for c-erbB-2 expression. CONCLUSIONS: c-erbB-2 overexpression was
      associated with a poor prognosis. Aggressive behaviour, recurrence, and
      metastatic potential do not appear to be related to cell cycle deregulation, but
      seem to be associated with the c-erbB-2 oncoprotein, which is involved in matrix
      degradation and proteolitic activity, in addition to increases in vessel
      permeability, endothelial cell growth, proliferation, migration, and
      differentiation. There was a correlation between c-erbB-2 oncoprotein expression
      and aggressive behaviour in SDCs.

PMID- 14645350
TI  - Thymidine phosphorylase expression and stromal vascularity in ductal carcinoma in
      situ of the breast.
AB  - AIMS: Periductal angiogenesis in ductal carcinoma in situ is associated with an
      increased risk of subsequently developing a recurrence. This study aimed to (1)
      identify the relation between periductal and stromal vascularity and recurrence
      and (2) determine whether thymidine phosphorylase (TP) is associated with
      angiogenesis or recurrence in ductal carcinoma in situ (DCIS). METHODS: Twenty
      cases of DCIS that did not subsequently recur, 20 that developed a subsequent in
      situ recurrence, and 12 that developed a subsequent invasive recurrence were
      investigated. Periductal and stromal (hotspot) microvessel density were
      determined quantitatively using antibodies to CD34 and von Willebrandt factor
      (vWF). TP expression by DCIS was assessed semiquantitatively using the H score
      method. RESULTS: Stromal and periductal microvessel density assessed by anti-vWF
      gave similar mean values, and showed a strong positive correlation. When
      angiogenesis was assessed with anti-CD34 this association was lost. Not only were
      the mean values for both types of microvessel density higher than those obtained
      with anti-vWF, but the periductal microvessel density was significantly greater
      than the stromal microvessel density. TP expression was associated with stromal
      microvessel density assessed with anti-vWF, but not with anti-CD34. TP expression
      was not related to recurrence. No significant difference was identified in TP
      expression or stromal vascularity in DCIS between cases that recurred as DCIS and
      those that recurred as invasive carcinoma. CONCLUSIONS: Recurrent in situ or
      invasive disease after excision of DCIS does not appear to be related to stromal
      microvessel density or to TP expression by DCIS cells.

PMID- 14645351
TI  - Red cell or serum folate? Results from the National Pathology Alliance
      benchmarking review.
AB  - AIMS: The National Pathology Alliance benchmarking review has completed five
      years of data collection and analysis of the workload and organisation of
      haematology laboratories in the UK. This study analyses variation in practice in
      how laboratories respond to a request to determine whether or not a patient has
      folate deficiency. METHODS: A three year analysis of workload data on the number
      of serum/plasma folate and red cell folate assays performed on an annual basis
      for the period 1 April 1999 to 31 March 2002. RESULTS: Three diagnostic testing
      strategies were found, namely: serum/plasma folate only, red cell folate only,
      and both serum/plasma folate and red cell folate. CONCLUSION: Evidence from the
      literature indicates that serum folate measurements provide equivalent
      information to red cell folate measurements when attempting to determine whether
      folate deficiency is present. There seems to be no basis for the routine testing
      of all samples for serum/plasma folate and a red cell folate.

PMID- 14645352
TI  - External quality assessment schemes raise standards: evidence from the UKNEQAS
      parasitology subschemes.
AB  - BACKGROUND: The burden of parasitic disease imported into the temperate zone is
      increasing, and in the tropics remains very high. Thus, high quality diagnostic
      parasitology services are needed, but to implement clinical governance a measure
      of quality of service is required. AIM: To examine performance in the United
      Kingdom National External Quality Assessment Scheme for Parasitology for evidence
      of improved standards in parasite diagnosis in clinical specimens. METHODS:
      Analysis of performance was made for the period 1986 to 2001, to look for trends
      in performance scores. RESULTS: An overall rise in performance in faecal and
      blood parasitology schemes was found from 1986 to 2001. This was seen
      particularly in the identification of ova, cysts, and larvae in the faecal
      scheme, the detection of Plasmodium ovale and Plasmodium vivax in the blood
      scheme, and also in the correct identification of non-malarial blood parasites.
      Despite this improvement, there are still problems. In the faecal scheme,
      participants still experience difficulty in recognising small protozoan cysts,
      differentiating vegetable matter from cysts, and detecting ova and cysts when
      more than one species is present. In the blood scheme, participants have problems
      in identifying mixed malarial infections, distinguishing between P ovale and P
      vivax, and estimating the percentage parasitaemia. The reasons underlying these
      problems have been identified via the educational part of the scheme, and have
      been dealt with by distributing teaching sheets and undertaking practical
      sessions. CONCLUSIONS: UK NEQAS for Parasitology has helped to raise the standard
      of diagnostic parasitology in the UK.

PMID- 14645353
TI  - Inequalities of primary care microbiology testing between hospital catchment
      areas.
AB  - AIMS: To compare differences in microbiology testing activity between general
      practices within and between five hospitals in two National Health Service (NHS)
      regions in England. METHODS: Retrospective capture of standardised microbiology
      testing activity from the laboratory computer databases. Six equivalent tests
      were identified and compared. Data were obtained for 174 general practices in
      eight primary care groups, served by two NHS hospital trusts and three public
      health laboratories. The total catchment population was 1,180,000 people.
      Comparative test activities were displayed graphically and differences in median
      test activity and the hospital activity distributions were examined by the
      Wilcoxon signed rank test. RESULTS: Median testing activity differed by 200%
      (urine) to 800% (wound swabs) between the trusts that performed the highest and
      the lowest number of tests, and from 300% to 1900% between the top and bottom 10%
      activity bands of general practices. Large and significant differences were found
      between the hospitals, irrespective of whether they belonged to the same trust,
      and irrespective of their geographical location. CONCLUSIONS: Large differences
      in microbiology testing exist within individual trust catchment areas in primary
      care, and there are also considerable differences between trusts. These
      inequalities may also introduce a selection bias into epidemiological and
      antibiotic resistance surveillance. This indicates a widespread need to examine
      and deal with the reasons responsible for these differences.

PMID- 14645354
TI  - Postprandial hypertriglyceridaemia in patients with Tangier disease.
AB  - BACKGROUND: Tangier disease (TD) is the phenotypic expression of rare familial
      syndromes with mutations in the ABCA1 transporter. TD results in extremely low
      high density lipoprotein (HDL) cholesterol and reduced low density lipoprotein
      cholesterol, with normal or mildly increased fasting triglyceride (TG)
      concentrations. Although there is a close relation between HDL cholesterol values
      and atherogenesis, the risk of coronary artery disease is variable in TD. Raised
      fasting or postprandial TG values frequently accompany low HDL cholesterol and
      can add to the risk of a vascular event. AIMS: To investigate the postprandial TG
      response in TD. PATIENTS AND METHODS: Five patients (three homozygotes (HTD) and
      two heterozygotes (hTD)) from one family were studied. One was defined by DNA
      analysis as homozygous for a new mutation (C2033A) resulting in truncation of the
      ABCA1 protein. Their TG concentrations were measured before and four, six, and
      eight hours after a standardised fat load and compared with a control group.
      RESULTS: Two patients with HTD had high fasting TG concentrations. The third
      patient with HTD, the two with hTD, and the control group had TG concentrations
      within the reference range. The patients with HTD had increased postprandial peak
      TG values when compared with those with hTD and controls. CONCLUSION: Patients
      with HTD, with or without fasting hypertriglyceridaemia, may have an increased TG
      response to a fatty meal. The small number of patients does not allow definitive
      conclusions to be made. However, postprandial hypertriglyceridaemia could be a
      reason why some patients with TD develop premature atherosclerosis.

PMID- 14645355
TI  - Genetic evolution of alpha fetoprotein producing gastric cancer.
AB  - BACKGROUND: Alpha fetoprotein (AFP) producing gastric cancer is an unusual form
      of aggressive adenocarcinoma with a complex histological picture, including
      enteroblastic and hepatoid differentiation. AIMS: To investigate the genetic
      events underlying the phenotypic diversity in AFP producing gastric cancer and
      the ability of these tumours to produce AFP ectopically. METHODS: Multiple foci
      from 19 AFP producing gastric adenocarcinomas were microdissected and loss of
      heterozygosity (LOH) analysis was performed with a panel of microsatellite
      markers on nine chromosomal arms. RESULTS: For informative cases, LOH was most
      frequently detected on 17p (100%), followed by 13q (88%), 3p (87%), 5q and 9p
      (80%), 11q (70%), 18q (58%), 16q (53%), and 8p (50%). The average fractional
      allelic loss was 0.72. LOH was detected either homogeneously throughout the
      microdissected foci, or only in some parts of the neoplastic foci for each case.
      Heterogeneous patterns of LOH indicated genetic progression and/or divergence in
      clonal evolution. Furthermore, in six cases with heterogeneous LOH of 13q, 13q
      LOH was restricted to immunohistochemically AFP positive neoplastic foci.
      CONCLUSION: AFP-GC arises as an aggressive clone with extensive LOH and high
      fractional allelic loss. The presence of heterogeneous patterns of LOH suggested
      that the AFP producing carcinoma foci might evolve through genetic progression
      and/or genetic divergence. Silencing of the crucial gene on 13q may be involved
      in the acquisition of the AFP producing phenotype.

PMID- 14645356
TI  - Medical educators' personal attitudes towards the necropsy.
AB  - AIMS: To explore the personal attitudes of medical educators to the necropsy.
      METHODS: A "theoretical sample" of individuals, with widely disparate views, was
      selected from University of Sheffield Medical School affiliated staff. These
      individuals underwent semi-structured interviews (in private) to elucidate their
      personal attitudes towards the necropsy (in relation to the possibility of their
      own necropsy or that of a close relative). RESULTS: Nine themes pertaining to
      personal attitudes towards the necropsy were identified. In general medical
      educators had a positive attitude towards the necropsy. CONCLUSIONS: This study
      suggests that medical educators still believe that the necropsy is of value in
      medical education, despite dramatic curricular revisions in the UK, declining
      necropsy rates, and adverse media attention to the necropsy.

PMID- 14645357
TI  - Development of immunoglobulin variable heavy chain gene consensus probes with
      conjugated 3' minor groove binder groups for monitoring minimal residual disease
      in childhood acute lymphoblastic leukaemia.
AB  - AIMS: To develop immunoglobulin heavy chain variable (VH) gene probes that are
      shorter and more flexible in position for monitoring minimal residual disease
      (MRD) in childhood leukaemia (ALL), using minor groove binder (MGB) technology.
      METHODS: All VH germline sequences registered in the database were aligned and
      the consensus regions were determined. The reliability of the MGB probes was
      compared with non-MGB probes in all 24 cases of ALL. RESULTS: Ten MGB probes (16
      to 18 mers) were designed that enabled all the germline sequences on the database
      to be analysed, whereas the conventional non-MGB probes (21 to 27 mers) did not
      allow the analysis of four of the VH1 and five of the VH3 germline sequences. The
      sequencing results in five of the 24 cases of ALL were not matched to the non-MGB
      probes. CONCLUSIONS: MGB technology allows shorter probes to be designed,
      enabling MRD to be detected in childhood ALL. This would provide a considerable
      reduction in cost for a large MRD study.

PMID- 14645358
TI  - Mannan binding lectin in febrile adults: no correlation with microbial infection
      and complement activation.
AB  - AIMS: To study the role of the mannan binding lectin (MBL) pathway of complement
      activation in the host defence to microbial infection in vivo, and the role of
      MBL in infectious mortality in non-selected patients. METHODS: A prospective
      observational study on 177 hospitalised medical patients with new onset fever.
      The presence, origin, and microbial cause of infection, the circulating MBL and
      complement activation product 3a (C3a), and the 28 day hospital course were
      determined. RESULTS: The patients had median MBL values similar to healthy blood
      donors: 18% of the patients and 14% of the blood donors had MBL deficiency, with
      values below 0.1 microg/ml. Median C3a was higher in patients with
      microbiologically confirmed infection than in those without, whereas there was no
      difference in MBL values or frequency of deficiency among patient groups with or
      without positive local cultures or bacteraemia. The mortality rate was 8% and the
      outcome groups did not differ in MBL. In febrile adults hospitalised in internal
      medicine wards, microbial infection induces complement activation, independently
      of MBL. CONCLUSIONS: The results argue against a predominant role for the MBL
      pathway of complement activation and a deficiency of MBL predisposing to serious
      and invasive microbial infection in non-selected adults.

PMID- 14645359
TI  - Hepatitis C virus genotype testing in paraffin wax embedded liver biopsies for
      specimen identification.
AB  - Despite advances in medical technology, careful specimen identification is still
      a fundamental principle of laboratory testing. If pathological samples are mixed
      up, especially in the case of extremely small biopsy samples, large amounts of
      time and energy may be wasted in correctly identifying the specimens. Recently,
      two liver biopsy specimens were mixed up in this department, and a new
      pathological technology was used to resolve the issue. Liver biopsy was performed
      on two patients with hepatitis C virus (HCV) infection. During sample transfer or
      tissue processing, the biopsy specimens were mixed up. Because the ABO blood
      group of the two patients was identical (type AB), the specimens were
      subsequently identified by analysing the HCV genotypes. RNA extracted from the
      paraffin wax embedded liver specimens was examined by a polymerase chain reaction
      based HCV genotype assay. This enabled the correct identification of the
      specimens, and each patient received the appropriate treatment on the basis of
      the accurate diagnosis.

PMID- 14645360
TI  - Multiple microcarcinoids in a patient with long standing ulcerative colitis.
AB  - A male patient with a 17 year history of intractable ulcerative colitis of the
      entire type was treated by total proctocolectomy. Colonoscopy before surgery did
      not identify dysplasia. Histological examination of the resected colorectum
      revealed that, in addition to chronic inflammatory infiltrates, there were 21
      areas of microcarcinoids located in the muscularis propria and in the superficial
      layer of the submucosa. Carcinoids may be more common than previously thought,
      and they may be a reactive phenomenon to a variety of factors in ulcerative
      colitis.

PMID- 14645361
TI  - Chronic granulomatous pleuritis caused by nocardia: PCR based diagnosis by
      nocardial 16S rDNA in pathological specimens.
AB  - Nocardiosis is an uncommon infection caused by the aerobic actinomycete nocardia.
      Identification of the pathogen is essential for the definitive diagnosis and for
      an effective treatment. This report describes a case of chronic granulomatous
      pleuritis caused by nocardia. A 59 year old Japanese man had a history of
      repeated pyothorax. Right pleural decortication and thoracic drainage were
      performed. Microbiological examinations of the drained fluid failed to identify a
      pathogen. Pathological examinations revealed Gram positive filamentous and
      branching bacilli in the granulomatous lesion of the pleura. Sequencing of the
      971 bp 16S ribosomal DNA extracted and amplified from paraffin wax embedded
      sections identified the microorganism as Nocardia sp. IFM 0860. The patient
      received sulfamethoxazol/trimethoprim and minocycline. Although the presence of a
      brain abscess was disclosed by systemic examination, the clinical course has been
      favourable. In this patient, polymerase chain reaction analysis of 16S ribosomal
      DNA in pathological specimens was useful in making an accurate diagnosis of
      nocardiosis and in determining the appropriate treatment.

PMID- 14645362
TI  - Carcinoma metastasis to unexpected synchronous lymphoproliferative disorder:
      report of three cases and review of literature.
AB  - Metastasis of one cancer to another cancer is rare. This report describes three
      cases in which low grade non-Hodgkin lymphomas were incidentally detected during
      the examination of lymph nodes removed as part of treatment of a previously
      diagnosed malignancy.

PMID- 14645363
TI  - Water transport becomes uncoupled from K+ siphoning in brain contusion, bacterial
      meningitis, and brain tumours: immunohistochemical case review.
AB  - Specimens of normal human brain, contused brain, brain with bacterial meningitis,
      and brain tumours were immunolabelled for aquaporin 4 (AQP4) and Kir4.1. In
      normal brain tissue, AQP4 and Kir4.1 were detected around the microvessels. In
      pathological brain tissue, AQP4 was upregulated in astrocytes in oedematous
      regions and Kir4.1 was upregulated in astrocytes in damaged brain. Changes in
      alpha syntrophin expression paralleled those of AQP4 and Kir4.1. The following
      hypothesis is proposed: in astrocytes, under normal conditions, AQP4 couples
      water transport with Kir4.1 mediated K+ siphoning, but in pathological states,
      AQP4 facilitates the flow of brain oedema fluid, and Kir4.1 buffers increased
      extracellular K+.

PMID- 14645364
TI  - Symptomatic laryngeal nodular chondrometaplasia: a clinicopathological study.
AB  - A 41 year old man with a history of politrauma presented with a nodular mass of
      the left false vocal cord, associated with progressive dysphonia, dyspnoea, and
      dysphagia. A computed tomography scan of the neck region showed a rounded and
      circumscribed mass without infiltration of the surrounding tissues. Histological
      investigation of the nodule revealed the presence of fibroelastic cartilaginous
      tissue, surrounded by a thin rim of fibrous tissue, with rare hypercellular
      areas, occasional binucleated cells, slight hyperchromasia, and an irregular
      nuclear profile. Mitotic activity was absent. The patient's history of laryngeal
      trauma, with the subsequent progressive onset of clinical symptoms, helps to
      distinguish the chondrometaplastic nature of this nodule from true laryngeal
      cartilaginous tumours, such as chondroma and low grade chondrosarcoma.

PMID- 14645365
TI  - Psammomatous carcinoid of the rectum.

PMID- 14645367
TI  - Small nucleolar RNA clusters in trypanosomatid Leptomonas collosoma. Genome
      organization, expression studies, and the potential role of sequences present
      upstream from the first repeated cluster.
AB  - Trypanosomatid small nucleolar RNA (snoRNA) genes are clustered in the genome.
      snoRNAs are transcribed polycistronically and processed into mature RNAs. In this
      study, we characterized four snoRNA clusters in Leptomonas collosoma. All of the
      clusters analyzed carry both C/D and H/ACA RNAs. The H/ACA RNAs are composed of a
      single hairpin, a structure typical to trypanosome and archaea guide RNAs. Using
      deletion and mutational analysis of a tagged C/D snoRNA situated within the
      snoRNA cluster, we identified 10-nucleotide flanking sequences that are essential
      for processing snoRNA from its precursor. Chromosome walk was performed on a
      snoRNA cluster, and a sequence of 700 bp was identified between the first repeat
      and the upstream open reading frame. Cloning of this sequence in an episome
      vector enhanced the expression of a tagged snoRNA gene in an orientation
      dependent manner. However, continuous transcript spanning of this region was
      detected in steady-state RNA, suggesting that snoRNA transcription also
      originates from an upstream-long polycistronic transcriptional unit. The 700-bp
      fragment may therefore represent an example of many more elements to be
      discovered that enhance transcription along the chromosome, especially when
      transcription from the upstream gene is reduced or when enhanced transcription is
      needed.

PMID- 14645368
TI  - Intimate evolution of proteins. Proteome atomic content correlates with genome
      base composition.
AB  - Discerning the significant relations that exist within and among genome sequences
      is a major step toward the modeling of biopolymer evolution. Here we report the
      systematic analysis of the atomic composition of proteins encoded by organisms
      representative of each kingdoms. Protein atomic contents are shown to vary
      largely among species, the larger variations being observed for the main
      architectural component of proteins, the carbon atom. These variations apply to
      the bulk proteins as well as to subsets of ortholog proteins. A pronounced
      correlation between proteome carbon content and genome base composition is
      further evidenced, with high G+C genome content being related to low protein
      carbon content. The generation of random proteomes and the examination of the
      canonical genetic code provide arguments for the hypothesis that natural
      selection might have driven genome base composition.

PMID- 14645369
TI  - DNA damage-binding proteins and heterogeneous nuclear ribonucleoprotein A1
      function as constitutive KCS element components of the interferon-inducible RNA
      dependent protein kinase promoter.
AB  - Protein kinase regulated by RNA (PKR) plays important roles in many cellular
      processes including virus multiplication and cell growth, differentiation, and
      apoptosis. The promoter of the PKR gene possesses a novel 15-bp element
      designated KCS, positioned upstream of a consensus interferon (IFN)-stimulated
      response element, that is required for both basal and interferon-inducible
      transcription. Protein binding to the KCS element is not dependent upon IFN
      treatment and correlates with transcriptional activity of the PKR promoter. The
      identity of KCS-binding proteins (KBP) that selectively bind at the KCS element
      is largely unknown, except for the transcription factor Sp1. We now have purified
      KBP from HeLa cell nuclear extracts by ion-exchange and DNA-affinity
      chromatography steps and then identified four constituent proteins of the KBP
      complex by mass spectrometry and immunochemistry: KBP120 and KBP45 are the
      damaged DNA-binding protein subunits, p127 DDB1 and p48 DDB2, respectively;
      KBP100 is the transcription factor Sp1; and KBP35 is the heterogeneous nuclear
      ribonucleoprotein A1. The steady-state levels of these four KCS-binding proteins
      in human cells are not altered by IFN treatment. Components of the KBP complex
      bind selectively and constitutively to the KCS element in the absence of IFN
      treatment, both in vitro as measured by competition electrophoretic mobility
      shift assay (EMSA) and DNA pull-down assays and in vivo as measured by chromatin
      immunoprecipitation assays. Depletion of DDB2 by antisense strategy reduces KBP
      complex formation by EMSA. These results provide new insight into the biochemical
      identity and activity of proteins involved in PKR promoter function.

PMID- 14645370
TI  - Functional domains of a pore-forming cardiotoxic protein, volvatoxin A2.
AB  - Volvatoxin A2 (VVA2), a novel pore-forming cardiotoxic protein was isolated from
      the mushroom Volvariella volvacea. We identified an N-terminal fragment (NTF) (1
      127 residues) of VVA2 as a domain for oligomerization by limited tryptic
      digestion. On preincubation of NTF with VVA2, NTF was found to inhibit VVA2
      hemolytic activity by inducing VVA2 oligomerization in the solution in the same
      manner as liposomes. By site-directed mutagenesis, the amphipathic alpha-helix B
      of NTF or VVA2 was shown to be indispensable for its biological functions.
      Interestingly, at a molar ratio of recombinant NTF (reNTF)/VVA2 as low as 0.01,
      reNTF was able to inhibit VVA2 hemolytic activity and induce VVA2
      oligomerization. This indicates that reNTF can trigger VVA2 oligomerization by a
      seeding effect. Furthermore, the recombinant C-terminal fragment (128-199
      residues) was found to be a functional domain that mediates the membrane binding
      of VVA2. We found a fragment localized at the C-terminal half of VVA2 containing
      beta6, -7, and -8, which is protected from protease digestion because of its
      insertion of a membrane. We also identified a putative heparin binding site (HBS)
      located in the VVA2 C terminus (166-194 residues), which was conserved among 10
      kinds of snake venom cardiotoxins. VVA2 or the reHBS fragment was shown to
      interact with sulfated glycoaminoglycans by affinity column chromatography. The
      finding of a higher number of glycoaminoglycans in the membrane of cardiac
      myocytes suggested that they could be the specific membrane target for VVA2.
      Taken together, these findings indicate that VVA2 contains two functional
      domains, NTF and CTF. The NTF domain is responsible for VVA2 oligomerization and
      the CTF domain for membrane binding and insertion. Our results support a model
      whereby the formation of VVA2 oligomeric pre-pore complexes precedes their
      membrane insertion.

PMID- 14645371
TI  - The Kinesin-related protein Costal2 associates with membranes in a Hedgehog
      sensitive, Smoothened-independent manner.
AB  - In Drosophila, Hedgehog (Hh) signal transduction has been shown to require a
      multiprotein complex (Hedgehog signaling complex (HSC)), which includes the
      Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused
      (Fu), and the transcription factor Cubitus interruptus (Ci). We present evidence
      that a biologically relevant fraction of the HSC is found in association with
      cellular membranes. We demonstrate that Cos2 is capable of tethering an exogenous
      protein to vesicular membranes and that Cos2 association with membranes is Hh
      sensitive. In addition, we demonstrate that Cos2 associates with membranes in
      cells that lack the transmembrane protein Smoothened (Smo) through a domain of
      Cos2 distinct from its recently characterized Smo binding domain. We suggest that
      an Hh-regulated membrane binding activity of Cos2 is part of the mechanism by
      which Cos2 contributes to Hh signaling. We propose a model in which there are two
      distinct HSCs with discrete subcellular localizations and activities: one is
      endosome-associated and facilitates production of a repressor form of Ci (HSC-R),
      and one is Smo-associated and promotes Ci activation (HSC-A). In response to Hh
      and through interaction with Cos2, Smo mediates both inhibition of the endosome
      associated HSC-R and activation of HSC-A at the plasma membrane.

PMID- 14645372
TI  - Structural basis for the coordinated regulation of transglutaminase 3 by guanine
      nucleotides and calcium/magnesium.
AB  - Transglutaminase 3 (TGase 3) is a member of a family of Ca2+-dependent enzymes
      that catalyze covalent cross-linking reactions between proteins or peptides.
      TGase 3 isoform is widely expressed and is important for effective epithelial
      barrier formation in the assembly of the cell envelope. Among the nine TGase
      enzyme isoforms known in the human genome, only TGase 2 is known to bind and
      hydrolyze GTP to GDP; binding GTP inhibits its transamidation activity but allows
      it to function in signal transduction. Here we present biochemical and
      crystallographic evidence for the direct binding of GTP/GDP to the active TGase 3
      enzyme, and we show that the TGase 3 enzyme undergoes a GTPase cycle. The crystal
      structures of active TGase 3 with guanosine 5'-O-(thiotriphosphate) (GTPgammaS)
      and GDP were determined to 2.1 and 1.9 A resolution, respectively. These studies
      reveal for the first time the reciprocal actions of Ca2+ and GTP with respect to
      TGase 3 activity. GTPgammaS binding is coordinated with the replacement of a
      bound Ca2+ with Mg2+ and conformational rearrangements that together close a
      central channel to the active site. Hydrolysis of GTP to GDP results in two
      stable conformations, resembling both the GTP state and the non-nucleotide bound
      state, the latter of which allows substrate access to the active site.

PMID- 14645373
TI  - Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte
      stimulating hormone.
AB  - Suppression of collagen synthesis is a major therapeutic goal in the treatment of
      fibrotic disorders. We show here that alpha-melanocyte-stimulating hormone (alpha
      MSH), a neuropeptide well known for its pigment-inducing capacity, modulates
      collagen synthesis and deposition. Alpha-MSH in vitro suppresses the synthesis of
      collagen types I, III, and V and down-regulates the secretion of procollagen type
      I C-terminal peptide (PICP) in human dermal fibroblasts treated with the
      fibrogenic cytokine transforming growth factor-beta1 (TGF-beta1). Alpha-MSH did
      not interfere with TGF-beta1 signaling, because TGF-beta1-induced expression of
      collagen mRNA was not affected, implying a posttranscriptional mechanism. Human
      dermal fibroblasts in vitro express a high affinity binding site for MSH, which
      was identified by reverse transcription PCR and immunofluorescence analysis as
      the melanocortin-1 receptor (MC-1R). Immunohistochemical studies on normal adult
      human skin confirmed MC-1R expression in distinct dermal fibroblastic cells. The
      MC-1R on fibroblasts appears to be functionally relevant because alpha-MSH
      increased the amount of intracellular cAMP, and coincubation with a synthetic
      peptide corresponding to the human Agouti signaling protein abrogated the
      inhibition of TGF-beta1-induced PICP secretion by alpha-MSH. To assess the in
      vivo relevance of these findings, a mouse model was used in which dermal fibrosis
      was induced by repetitive intracutaneous injections with TGF-beta1. The inductive
      activity of TGF-beta1 on collagen deposition and the number of dermal cells
      immunoreactive for vimentin and alpha-smooth muscle actin was significantly
      suppressed by injection of alpha-MSH. Melanocortins such as alpha-MSH may
      therefore represent a novel class of modulators with potential usefulness for the
      treatment of fibrotic disorders.

PMID- 14645374
TI  - Primate antisaccade. II. Supplementary eye field neuronal activity predicts
      correct performance.
AB  - Neuronal activities were recorded in the supplementary eye field (SEF) of 3
      macaque monkeys trained to perform antisaccades pseudorandomly interleaved with
      prosaccades, as instructed by the shape of a central fixation point. The
      prosaccade goal was indicated by a peripheral stimulus flashed anywhere on the
      screen, whereas the antisaccade goal was an unmarked site diametrically opposite
      the flashed stimulus. The visual cue was given immediately after the instruction
      cue disappeared in the immediate-saccade task, or during the instruction period
      in the delayed-saccade task. The instruction cue offset was the saccade gosignal.
      Here we focus on 92 task-related neurons: visual, eye-movement, and
      instruction/fixation neurons. We found that 73% of SEF eye-movement-related
      neurons fired significantly more before anti-saccades than prosaccades. This
      finding was analyzed at 3 levels: population, single neuron, and individual
      trial. On individual antisaccade trials, 40 ms before saccade, the firing rate of
      eye-movement-related neurons was highly predictive of successful performance. A
      similar analysis of visual responses (40 ms astride the peak) gave less-coherent
      results. Fixation neurons, activated during the initial instruction period (i.e.,
      after the instruction cue but before the stimulus) always fired more on
      antisaccade than on prosaccade trials. This trend, however, was statistically
      significant for only half of these neurons. We conclude that the SEF is
      critically involved in the production of antisaccades.

PMID- 14645375
TI  - In vivo recordings of long-term potentiation and long-term depression in the
      dentate gyrus of the neonatal rat.
AB  - Previous in vitro studies demonstrated that long-term potentiation (LTP) could be
      elicited at medial perforant path (MPP) synapses onto hippocampal granule cells
      in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at
      perforant path synapses could not be induced until at least days 9 or 10 and then
      in only a small percentage of animals. Because several characteristics of the
      oldest granule cells are adult-like on day 7, we re-examined the possibility of
      eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old
      rats to further elucidate the occurrence and magnitude of LTP in neonates. With
      halothane anesthesia, all animals in each age group exhibited synaptic plasticity
      of the excitatory postsynaptic potential following high-frequency stimulation of
      the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an
      average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%)
      was induced in 40% of the animals, while short-term potentiation (STP) alone
      (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the
      remaining 10%. Data were similar for all ages combined. In addition, the N-methyl
      d-aspartate (NMDA) antagonist (R,S)-3-(2-carboxypiperazin-4-yl)propyl-1
      phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the
      percentage of animals expressing LTD alone for all ages combined. These results
      demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7
      day-old rats, supporting our premise that at least a portion of the dentate gyrus
      is functional at this early age.

PMID- 14645377
TI  - Cue-evoked firing of nucleus accumbens neurons encodes motivational significance
      during a discriminative stimulus task.
AB  - The nucleus accumbens (NAc) has long been thought of as a limbic-motor interface.
      Despite behavioral and anatomical evidence in favor of this idea, little is known
      about how NAc neurons encode information about motivationally relevant
      environmental cues and use this information to affect motor action. We therefore
      investigated the firing of these neurons during the performance of a
      discriminative stimulus (DS) task using simultaneous multiple single-unit
      recordings in rats. In this task, two stimuli are randomly presented to the
      animal: a DS, which signals the availability of a sucrose reward contingent on an
      operant response, and a similar but nonrewarded stimulus (NS). Subpopulations of
      NAc neurons increased or decreased their firing in association with several
      distinct components of the task. In this paper, we investigate cue- and operant
      responsive neurons. Neurons excited and inhibited by cues showed larger firing
      changes in response to the DS than the NS and larger changes when the animal made
      an operant response to the cue than when the animal failed to respond.
      Excitations during operant responding were not modulated by the information
      contained by the cue, whereas inhibitions during operant responding were somewhat
      larger if the operant response occurred during the DS and somewhat smaller if
      they occurred in the absence of a cue. These results are consistent with the
      hypothesis that the firing of subpopulations of NAc neurons encode both the
      predictive value of environmental stimuli and the specific motor behaviors
      required to respond to them.

PMID- 14645378
TI  - Firing of nucleus accumbens neurons during the consummatory phase of a
      discriminative stimulus task depends on previous reward predictive cues.
AB  - The nucleus accumbens (NAc) plays an important role in both appetitive and
      consummatory behavior. To examine how NAc neurons encode information during
      reward consumption, we recorded the firing activity of rat NAc neurons during the
      performance of a discriminative stimulus task. In this task, the animal must make
      an operant response to an intermittently presented cue to obtain a sucrose reward
      delivered in a reward receptacle. Uncued entries to the receptacle were not
      rewarded. Both excitations and inhibitions during reward consumption were
      observed, but substantially more neurons were inhibited than excited. These
      excitations and inhibitions began when the animal entered the reward receptacle
      and ended when the animal exited the receptacle. Both excitations and inhibitions
      were much smaller or nonexistent when the animal made uncued entries into the
      reward receptacle. In one set of experiments, we randomly withheld the reward in
      some cued trials that would otherwise have been rewarded. Excitations and
      inhibitions were of similar magnitude whether or not the reward was delivered.
      This indicates that the sensory stimulus of reward does not drive these phasic
      responses; instead, the reward-associated responses may be driven by the
      conditioned stimuli associated with reward, or they may encode information about
      consummatory motor activity. Another population of NAc neurons was excited on
      exit from the reward receptacle. Many of these excitations persisted for tens of
      seconds after the receptacle exit and showed a significant inverse correlation
      with the rate of uncued operant responding. These findings are consistent with a
      contribution of NAc neurons to both reward consummatory and reward seeking
      behavior.

PMID- 14645379
TI  - Dietary prenatal choline supplementation alters postnatal hippocampal structure
      and function.
AB  - Choline, a compound present in many foods, has recently been classified as an
      essential nutrient for humans. Studies with animal models indicate that the
      availability of choline during the prenatal period influences neural and
      cognitive development. Specifically, prenatal choline supplementation has been
      shown to enhance working memory and hippocampal long-term potentiation (LTP) in
      adult offspring. However, the cellular mechanisms underlying these effects remain
      unclear. Here we report that choline supplementation, during a 6-day gestational
      period, results in greater excitatory responsiveness, reduced slow
      afterhyperpolarizations (sAHPs), enhanced afterdepolarizing potentials (ADPs),
      larger somata, and greater basal dendritic arborization among hippocampal CA1
      pyramidal cells studied postnatally in juvenile rats (20-25 days of age). These
      data indicate that dietary supplementation with a single nutrient, choline,
      during a brief, critical period of prenatal development, alters the structure and
      function of hippocampal pyramidal cells.

PMID- 14645381
TI  - Neuronal activity in motor cortical areas reflects the sequential context of
      movement.
AB  - Natural actions can be described as chains of simple elements, whereas individual
      motion elements are readily concatenated to generate countless movement
      sequences. Sequence-specific neurons have been described extensively, suggesting
      that the motor system may implement temporally complex motions by using such
      neurons to recruit lower-level movement neurons modularly. Here, we set out to
      investigate whether activity of movement-related neurons is independent of the
      sequential context of the motion. Two monkeys were trained to perform linear arm
      movements either individually or as components of double-segment motions.
      However, comparison of neuronal activity between these conditions is delicate
      because subtle kinematic variations generally occur within different contexts. We
      therefore used extensive procedures to identify the contribution of variations in
      motor execution to differences in neuronal activity. Yet, even after application
      of these procedures we find that neuronal activity in the motor cortex (PMd and
      M1) associated with a given motion segment differs between the two contexts.
      These differences appear during preparation and become even more prominent during
      motion execution. Interestingly, despite context-related differences on the
      single-neuron level, the population as a whole still allows a reliable readout of
      movement direction regardless of the sequential context. Thus the direction of a
      movement and the sequential context in which it is embedded may be simultaneously
      and reliably encoded by neurons in the motor cortex.

PMID- 14645380
TI  - Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the
      pancreas evoked by hypoglycemia in rat.
AB  - Circulating glucose levels significantly affect vagal neural activity, which is
      important in the regulation of pancreatic functions. Little is known about the
      mechanisms involved. This study investigates the neural pathways responsible for
      hypoglycemia-induced vagal efferent signaling to the pancreas and identifies the
      neurotransmitters involved. Vagal pancreatic efferent nerve activities were
      recorded in anesthetized rats. Insulin-induced hypoglycemia, a decrease of blood
      glucose levels from 114 +/- 5 to 74 +/- 6 mg dl(-1), stimulated an increase in
      pancreatic efferent nerve firing from a basal rate of 1.1 +/- 0.3 to 19 +/- 3
      impulses 30 s(-1). In contrast, vagal primary afferent neuronal discharges
      recorded in the nodose ganglia were unaltered by systemic hypoglycemia. Vagal
      afferent rootlet section plus splanchnicotomy had no effect on hypoglycemia
      induced vagal efferent firing, suggesting a central site of action. Decerebration
      reduced the increase in nerve firing stimulated by hypoglycemia from 21 +/- 4 to
      9.6 +/- 2 impulses 30 s(-1). Chemical ablation of the lateral hypothalamic area,
      but not the arcuate nucleus, inhibited pancreatic nerve firing evoked by
      hypoglycemia. Microinjection of the orexin-A receptor antagonist SB-334867 into
      the dorsal motor nucleus of the vagus (DMV) inhibited pancreatic nerve firing
      evoked by insulin-induced hypoglycemia by 56%. In contrast, injection of orexin-A
      (20 pmol) into the DMV elicited a 30-fold increase in pancreatic nerve firing. We
      concluded that systemic hypoglycemia stimulates pancreatic efferent nerve firing
      through a central mechanism. Full expression of pancreatic nerve activities
      during hypoglycemia requires both the forebrain and the brain stem. In addition
      to activating neurons in the brain stem, central neuroglucopenia activates
      subpopulations of neurons in the lateral hypothalamic area that contain orexin.
      The released orexin acts on DMV neurons to stimulate pancreatic efferent nerve
      activities and thus regulate pancreatic functions.

PMID- 14645382
TI  - Haptic synthesis of shapes and sequences.
AB  - Haptic perception of shape is based on kinesthetic and tactile information
      synthesized across space and time. We studied this process by having subjects
      move along the edges of multisided shapes and then remember and reproduce the
      shapes. With eyes closed, subjects moved a robot manipulandum whose force field
      was programmed to simulate a quadrilateral boundary in a horizontal plane. When
      subjects then reproduced the quadrilateral using the same manipulandum, with eyes
      still closed but now with the force field set to zero, they made consistent
      errors, overestimating the lengths of short segments and underestimating long
      ones, as well as overestimating acute angles and underestimating obtuse ones.
      Consequently their reproductions were more regular than the shapes they had
      experienced. When subjects felt the same quadrilaterals with the same
      manipulandum but drew them on a vertical screen with visual feedback, they made
      similar errors, indicating that their distortions reflected mainly perceptual
      rather than motor processes. In a third experiment, subjects explored the 3 sides
      of an open shape in a fixed order. The results revealed a temporal pattern of
      interactions, where the lengths and angles of previously explored segments
      influenced the drawing of later segments. In all tasks, our subjects were as
      accurate as subjects in earlier studies who haptically explored only single lines
      or angles, suggesting that the mental processes that synthesize haptic data from
      multiple segments into complete shapes do not introduce any net error.

PMID- 14645383
TI  - Low-threshold L-type calcium channels in rat dopamine neurons.
AB  - Ca(2+) channel subtypes expressed by dopaminergic (DA) neurons in the substantia
      nigra pars compacta (SNc) were studied using whole cell patch-clamp recordings
      and blockers selective for different channel types (L, N, and P/Q). Nimodipine
      (Nim, 2 microM), omega-conotoxin GVIA (Ctx, 1 microM), or omega-agatoxin IVA
      (Atx, 50 nM) blocked 27, 36, and 37% of peak whole cell Ca(2+) channel current,
      respectively, indicating the presence of L-, N-, and P-type channels. Nim blocked
      approximately twice as much Ca(2+) channel current near activation threshold
      compared with Ctx or Atx, suggesting that small depolarizations preferentially
      opened L-type versus N- or P-type Ca(2+) channels. N- and L-channels in DA
      neurons opened over a significantly more negative voltage range than those in rat
      dorsal root ganglion cells, recorded from using identical conditions. These data
      provide an explanation as to why Ca(2+)-dependent spontaneous oscillatory
      potentials and rhythmic firing in DA neurons are blocked by L-channel but not N
      channel antagonists and suggest that pharmacologically similar Ca(2+) channels
      may exhibit different thresholds for activation in different types of neurons.

PMID- 14645384
TI  - Changes in the readily releasable pool of transmitter and in efficacy of release
      induced by high-frequency firing at Aplysia sensorimotor synapses in culture.
AB  - Synaptic transmission at the sensory neuron-motor neuron synapses of Aplysia,
      like transmission at many synapses of both vertebrates and invertebrates, is
      increased after a short burst of high-frequency stimulation (HFS), a phenomenon
      known as posttetanic potentiation (PTP). PTP is generally attributable to an
      increase in transmitter release from presynaptic neurons. We investigated whether
      changes in the readily releasable pool of transmitter (RRP) contribute to the
      potentiation that follows HFS. We compared the changes in excitatory postsynaptic
      potentials (EPSPs) evoked with action potentials to changes in the RRP as
      estimated from the asynchronous transmitter release elicited by a hypertonic
      solution. The changes in the EPSP were correlated with changes in the RRP, but
      the changes matched quantitatively only at connections whose initial synaptic
      strength was greater than the median for all experiments. At weaker connections,
      the increase in the RRP was insufficient to account for PTP. Weaker connections
      initially released a smaller fraction of the RRP with each EPSP than stronger
      ones, and this fraction increased at weaker connections after HFS. Moreover, the
      initial transmitter release in response to the hypertonic solution was
      accelerated after HFS, indicating that the increase in the efficacy of release
      was not restricted to excitation-secretion coupling. Modulation of the RRP and of
      the efficacy of release thus both contribute to the enhancement of transmitter
      release by HFS.

PMID- 14645385
TI  - How self-initiated memorized movements become automatic: a functional MRI study.
AB  - We used functional magnetic resonance imaging (fMRI) and dual tasks to
      investigate the physiology of how movements become automatic. Normal subjects
      were asked to practice some self-initiated, self-paced, memorized sequential
      finger movements with different complexity until they could perform the tasks
      automatically. Automaticity was evaluated by having subjects perform a secondary
      task simultaneously with the sequential movements. Our secondary task was a
      letter-counting task where subjects were asked to identify the number of times a
      target letter from the letter sequences was seen. Only the performances that
      achieved high accuracy in both single and dual tasks were considered automatic.
      The fMRI results before and after automaticity was achieved were compared. Our
      data showed that for both conditions, sequential movements activated similar
      brain regions. No additional activity was observed in the automatic condition.
      There was less activity in bilateral cerebellum, presupplementary motor area,
      cingulate cortex, left caudate nucleus, premotor cortex, parietal cortex, and
      prefrontal cortex during the automatic stage. These findings suggest that most of
      the motor network participates in executing automatic movements and that it
      becomes more efficient as movements become more automatic. Our results do not
      provide evidence for any area to become more activated for automatic movements.

PMID- 14645387
TI  - Targets of stress-induced oxidative damage in plant mitochondria and their impact
      on cell carbon/nitrogen metabolism.
AB  - Plant mitochondria link the cellular processes of carbon and nitrogen metabolism
      through the tricarboxylic acid cycle and the photorespiratory cycle.
      Environmental stresses lead to damage of specific mitochondrial targets through
      the direct action of reactive oxygen species and indirect action of lipid
      peroxidation products. Uncovering the extent of this damage, the exact sites of
      damage and the mechanisms of avoidance and/or repair remains a largely
      unresearched challenge for plant scientists. Damage to Fe-S centres and proteins
      containing lipoic acid moieties appear to predominate in current reports.
      Substantial evidence that both TCA cycle and photorespiratory capacity of
      mitochondria are sensitive sites for damage is highlighted and the implications
      for mitochondrial-dependent carbon and nitrogen metabolism are discussed.

PMID- 14645386
TI  - Photolysis of postsynaptic caged Ca2+ can potentiate and depress mossy fiber
      synaptic responses in rat hippocampal CA3 pyramidal neurons.
AB  - The induction of mossy fiber-CA3 long-term potentiation (LTP) and depression
      (LTD) has been variously described as being dependent on either pre- or
      postsynaptic factors. Some of the postsynaptic factors for LTP induction include
      ephrin-B receptor tyrosine kinases and a rise in postsynaptic Ca2+ ([Ca2+]i).
      Ca2+ is also believed to be involved in the induction of the various forms of LTD
      at this synapse. We used photolysis of caged Ca2+ compounds to test whether a
      postsynaptic rise in [Ca2+]i is sufficient to induce changes in synaptic
      transmission at mossy fiber synapses onto rat hippocampal CA3 pyramidal neurons.
      We were able to elevate postsynaptic [Ca2+]i to approximately 1 microm for a few
      seconds in pyramidal cell somata and dendrites. We estimate that CA3 pyramidal
      neurons have approximately fivefold greater endogenous Ca2+ buffer capacity than
      CA1 neurons, limiting the rise in [Ca2+]i achievable by photolysis. This [Ca2+]i
      rise induced either a potentiation or a depression at mossy fiber synapses in
      different preparations. Neither the potentiation nor the depression was
      accompanied by consistent changes in paired-pulse facilitation, suggesting that
      these forms of plasticity may be distinct from synaptically induced LTP and LTD
      at this synapse. Our results are consistent with a postsynaptic locus for the
      induction of at least some forms of synaptic plasticity at mossy fiber synapses.

PMID- 14645388
TI  - Global aspects of C/N interactions determining plant-environment interactions.
AB  - The atomic C:N ratio in photolithotrophs is a function of their content of
      nucleic acids, proteins, lipids, polysaccharides, and other organic materials,
      and varies from about 5 in some protein-rich microalgae to much higher values in
      macroalgae and in higher plants with relatively more structural and energy
      storage materials. These differences in C:N ratios among organisms means that
      there is more N assimilation by photosynthetic organisms in the oceans than on
      land despite the near equality of global photosynthetic C assimilation rates in
      the two environments. Aquatic organisms obtain inorganic C and inorganic N from
      the surrounding water. Terrestrial photolithotrophs obtain inorganic C,
      dinitrogen (by diazotrophy) and some combined N from the atmosphere, with the
      remaining combined N coming from the soil. The nitrogen cost of growth (biomass
      production rate per unit plant N) varies with the C:N ratio and specific growth
      rate of the organism. The C:N ratio of plants can be increased with no, or
      minimal, decrease in growth rate by switching from N-containing to N-free solutes
      involved in, for example, UV-B screening or by reducing the content of particular
      proteins. The water cost of growth (water lost per unit biomass gain) in
      terrestrial plants is a function of N supply and of C supply; water cost is lower
      with higher N and C availability. Water supply is also important in determining
      denitrification rates on land and on N (and C) fluxes from terrestrial to aquatic
      systems.

PMID- 14645389
TI  - Form of Al changes with Al concentration in leaves of buckwheat.
AB  - Buckwheat (Fagopyrum esculentum Moench. cv. Jianxi) is known as an Al
      accumulating plant. The process leading to the accumulation of Al in the leaves
      was investigated, focusing on the chemical form of Al using 27Al-nuclear magnetic
      resonance. Leaves with different Al concentrations were prepared by growing
      buckwheat on a very acidic soil (Andosol) amended with or without CaCO3 (1 or 3 g
      x kg-1 soil). When the Al concentration of the leaves was lower, only one major
      signal was observed at a chemical shift of 16.1 ppm, which was assigned to an Al
      oxalate complex at a 1:3 ratio. However, when the Al concentration of the leaves
      increased to a high level (e.g. 12 g Al kg-1), an additional signal at a chemical
      shift of 11.2 ppm was observed. This signal was assigned to an Al-citrate complex
      at a 1:1 ratio. In the leaf with a high Al concentration, both Al-oxalate (1:3)
      and Al-citrate (1:1) were detected in marginal and middle parts, while only Al
      oxalate was detected in the basal part. The oxalate concentration did not differ
      very much between leaves with low and high Al concentrations at the same
      position, while citrate concentration significantly increased with increasing Al
      concentration when the oxalate/Al ratio became lower than 3.0. As the Al-citrate
      complex has been demonstrated to be the form of transport in the xylem, the
      results suggest that when internal oxalate is enough to form a complex with Al at
      a 3:1 ratio in the leaves with a low Al concentration, Al-citrate converts to Al
      oxalate. However, this conversion does not occur in the leaves with a very high
      Al concentration, resulting in the coexistence of both Al-oxalate and Al-citrate
      complexes.

PMID- 14645390
TI  - The rate of CO(2) assimilation controls the expression and activity of glutamine
      synthetase through sugar formation in sunflower (Helianthus annuus L) leaves.
AB  - The expression and activity of glutamine synthetase (GS, EC 6.3.1.2) were
      examined in relation to the rate of CO2 assimilation in sunflower (Helianthus
      annuus L.) leaves. Intact plants were kept in the dark for 72 h and subsequently
      exposed to light under different atmospheric CO2 concentrations (100, 400 and
      1200 microl l-1) for 6 h. The in vivo rates of net CO2 assimilation correlated
      with atmospheric CO2 concentrations. Stomatal conductances and transpiration
      rates remained largely unaffected by CO2 levels. Exposure of the plants to
      increasing CO2 concentrations in the light caused concomitant increases in the
      contents of starch and soluble sugars and a decrease in the nitrate content in
      leaves. Both cytosolic and chloroplastic (GS2) GS activities were higher at
      elevated CO2. A greater accumulation of GS2 mRNA was also observed under high
      CO2. Exogenous supply of sucrose to detached leaves greatly increased the levels
      of GS enzyme activity and of mRNA for chloroplastic GS in the dark. These results
      indicate that GS expression and activity in sunflower leaves are modulated by the
      rate of CO2 assimilation, and that photosynthesized sugars are presumably
      involved as regulatory metabolites.

PMID- 14645391
TI  - Molecular analysis of programmed cell death during senescence in Arabidopsis
      thaliana and Brassica oleracea: cloning broccoli LSD1, Bax inhibitor and serine
      palmitoyltransferase homologues.
AB  - This study was undertaken to characterize the programmed cell death (PCD)
      processes that occur during detached and natural on-plant senescence and
      correlate them with the expression of putative regulatory genes that may be
      involved in the process. DNA fragmentation and TUNEL analysis of broccoli florets
      showed that DNA was processed into fragments of approximately 180 bp after 48 h
      of harvest-induced tissue senescence. Characteristic laddering patterns were also
      visible in Arabidopsis leaves undergoing natural on-plant senescence and during
      detached senescence. Several recently isolated plant proteins have been assigned
      a PCD role, for example, the zinc finger containing protein, LSD1 (lesion
      simulating disease); Bax inhibitor (BI); and serine palmitoyltransferase (SPT),
      an enzyme in the sphingolipid signalling pathway. Two cDNAs encoding each of
      these proteins were isolated from broccoli (BoBI-1, BoBI-2, BoLSD1, BoLSD2,
      BoSPT1, BoSPT2), and the mRNAs increased during harvest-induced senescence in
      floret tissue. Expression of the Arabidopsis homologues (AtBI-1, AtLSD1, AtSPT1)
      were also characterized during detached leaf senescence in Arabidopsis leaves.
      AtBI-1 expression was constitutively expressed during detached senescence, AtLSD1
      expression remained constitutively low, and AtSPT1 expression increased during
      detached senescence.

PMID- 14645392
TI  - Highly conserved protein kinases involved in the regulation of carbon and amino
      acid metabolism.
AB  - It has been clear for over a decade and a half that ancient signalling pathways
      controlling fundamental cellular processes are highly conserved throughout the
      eukaryotes. Two plant protein kinases, sucrose non-fermenting 1 (SNF1)-related
      protein kinase (SnRK1) and general control non-derepressible 2 (GCN2)-related
      protein kinase are reviewed here. These protein kinases show an extraordinary
      level of conservation with their fungal and animal homologues given the span of
      time since they diverged from them. However, close examination of the signalling
      pathways in which they operate also reveals intriguing differences in activation
      and function.

PMID- 14645393
TI  - The histone-like protein H1-S and the response of tomato leaves to water deficit.
AB  - Linker histone protein variants are expressed in different tissues, at various
      developmental stages or induced by specific environmental conditions in many
      plant species. In most cases, the function of these proteins remains unknown. In
      the work presented here an antisense strategy has been used to study the function
      of the drought-induced linker histone, H1-S of tomato. Three independent H1-S
      antisense tomato mutants, selected for their inability to accumulate H1-S in
      response to water stress, were studied. These mutants have been characterized at
      the physiological and morphological levels. Histone H1-S antisense transgenic
      plants developed normally indicating that H1-S does not play an important role in
      the basal functions of tomato development. No differences were detected in
      chromatin organization, excluding a structural role for H1-S in chromatin
      organization. However, differences between the wild-type and antisense plants
      were observed in leaf anatomy and physiological activities. This analysis
      indicates that H1-S has more than one function, at different times, in
      controlling plant water status, highlighting the complexity of the water stress
      response.

PMID- 14645394
TI  - The rice pyruvate decarboxylase 3 gene, which lacks introns, is transcribed in
      mature pollen.
AB  - The rice pyruvate decarboxylase 3 gene (PDC3), which has no introns, was
      previously postulated to be a pseudogene because no PDC3 mRNA had been detected,
      even under anaerobic conditions. However, in this study, it was found that rice
      PDC3 transcripts accumulated in panicles after heading. Within anthers obtained
      from the panicles, PDC3 was shown to be transcribed in mature pollen by in situ
      hybridization. These results suggest that the rice PDC3 is a functional gene. Its
      product may play a role in aerobic alcoholic fermentation in mature pollen.

PMID- 14645395
TI  - Identification of aluminium-regulated genes by cDNA-AFLP in rice (Oryza sativa
      L.): aluminium-regulated genes for the metabolism of cell wall components.
AB  - Aluminium (Al) toxicity is the major factor limiting crop productivity in acid
      soils. To investigate the molecular mechanisms of Al toxicity and Al tolerance of
      rice, cDNA-amplified fragment length polymorphism (cDNA-AFLP) was used for
      identifying Al-regulated genes in roots of an Al-tolerant tropical upland rice,
      Azucena, and an Al-sensitive lowland rice, IR1552. Nineteen function-known genes
      were found among 34 transcript-derived fragments (TDFs) regulated by Al stress.
      The results indicate that Al stress could induce the biosynthesis of lignin and
      other cell wall components in roots. Temporal expression patterns of 14 genes
      were identified between the two varieties. In silico mapping was performed for
      all the 33 unique genes. Two genes for a function-unknown protein and for a
      ubiquitin-like protein, respectively, were mapped on the interval with the common
      QTL (quantitative trait loci) for Al tolerance in rice on chromosome 1.

PMID- 14645396
TI  - Implementing ASCO's strategic plan 2003: diverse membership needs, prevention,
      and patient partnerships.

PMID- 14645403
TI  - David A. Karnofsky Award lecture. Imatinib as a paradigm of targeted therapies.

PMID- 14645404
TI  - Estimating the impact of new clinical trial proven cancer therapy and cancer
      chemoprevention on population mortality: the Karnofsky Memorial lecture.
AB  - PURPOSE: The 31-year "war on cancer" has focused largely on therapeutic (as
      opposed to preventative) cancer research, which, in both the public and private
      sector, has received the majority of funding. Meanwhile the prevention of cancer
      has received less attention. PATIENTS AND METHODS: We analyzed eight positive
      phase III therapeutic trials of the Southwest Oncology Group, and estimated how
      the observed improvements in survival from the new therapies would impact
      mortality at the population level (utilizing Surveillance, Epidemiology, and End
      Results-data). We compared these results with the impact of the Prostate Cancer
      Prevention Trial. The measure of impact was person-years saved in the first 5
      years. RESULTS: Estimates of person-years saved in the first 5 years included
      28,534 from improved treatment of localized bladder cancer and 26,241 from
      improved treatment of advanced lung cancer, representing, respectively, 31.4% and
      2.8% of the person-years which could have been saved for these diseases (the
      "relative impact of new treatment on survival"). The new therapies from all eight
      positive phase III trials would have saved 114,641 person-years over the first 5
      years. The estimate from the Prostate Cancer Prevention Trial was 99,441 person
      years over the first 5 years. CONCLUSION: New cancer therapies have a proven and
      quantifiable impact on population mortality. Successful cancer prevention has a
      similarly large impact. However, federal funding for cancer prevention is less
      than half that of cancer treatment. As a result of its enormous potential for
      extending life, cancer prevention warrants increased funding and support from
      federal funding agencies.

PMID- 14645405
TI  - American Cancer Society Award lecture. Psychological care of patients: psycho
      oncology's contribution.
AB  - The centuries-old stigma attached to cancer precluded patients' being told their
      diagnoses, and thus, delayed any exploration of how they dealt with their
      illness. This situation changed in the United States in the 1970s when patients
      began to be told their cancer diagnosis, permitting the first formal study of the
      psychological impact of cancer. However, a second and equally long-held stigma
      attached to mental illness has been another barrier and this has kept patients
      from being willing to acknowledge their psychological problems and to seek
      counseling. This "double stigma" has slowed the development of psycho-oncology.
      However, we began to see rapid changes occurring in the last quarter of the 20th
      century. Valid assessment instruments were developed which were used in well
      designed studies. Data from these studies and clinical observations led to
      increased recognition that psychosocial services are needed by many patients and
      provide significant assistance in coping with illness. Psycho-oncology has two
      dimensions: first, the study of the psychological reaction of patients at all
      stages of the disease, as well as of the family and oncology staff; second,
      exploring the psychological, social, and behavioral factors that impact on cancer
      risk and survival. Psycho-oncology now has a recognized role within the oncologic
      community through clinical care, research, and training as it relates to
      prevention of cancer through lifestyle changes, evaluation of quality of life,
      symptom control, palliative care and survivorship. Presently, there are
      sufficient research studies from which standards of care have been established.
      Both evidence and consensus-based clinical practice guidelines have been
      promulgated. It now possible to monitor the quality of existing psychosocial
      services by using these benchmarks of quality that have evolved in recent years.

PMID- 14645406
TI  - Therapeutic strategies in gastric cancer.
AB  - Gastric cancer continues to be a major public health problem and is the second
      most common cause of cancer-related deaths in the world. These statistics led the
      American Society of Clinical Oncology (ASCO) International Affairs Committee to
      choose gastric cancer as the topic for the International Symposium held at the
      2003 ASCO Annual Meeting. Dr Yoshiaki Ito will discuss the role of RUNX3 in the
      genesis and progression of human gastric cancer. Dr Pelayo Correa will present a
      compelling argument on the use of Helicobacter pylori therapy and antioxidants in
      selected high-risk population as chemoprevention strategies for gastric cancer.
      The controversy regarding the role of extended lymph node dissection for gastric
      cancer will be discussed by Dr Cornelis J.H. Van De Velde and Dr Mitsuru Sasako.
      Dr Van De Velde will present the European surgical approach to gastric cancer,
      and Dr Sasako will review the Japanese experience. The issues of whether certain
      patients benefit from more aggressive surgical dissection and the potential risks
      compared with benefits will also be discussed. Dr John Macdonald will discuss the
      role of adjuvant chemotherapy and adjuvant chemoradiotherapy in resected gastric
      cancer, as well as the role of chemotherapy in metastatic gastric cancer.

PMID- 14645407
TI  - Chemoprevention of gastric cancer: has the time come?

PMID- 14645408
TI  - Improving treatment outcome for gastric cancer: the role of surgery and adjuvant
      therapy.

PMID- 14645409
TI  - Principles of surgical treatment for curable gastric cancer.

PMID- 14645410
TI  - Chemotherapy in the management of gastric cancer.

PMID- 14645411
TI  - Antiangiogenic therapy at a crossroads: clinical trial results and future
      directions.

PMID- 14645413
TI  - Role of molecular and genetic markers in breast cancer treatment decisions.

PMID- 14645415
TI  - EGF receptor as a therapeutic target: patient selection and mechanisms of
      resistance to receptor-targeted drugs.
AB  - Emerging results from clinical trials of epidermal growth factor receptor (EGFR)
      inhibitors indicate good tolerability and at best modest to no clinical activity
      in a variety of human carcinomas. The lack of molecular evidence to suggest a
      pathogenic role for the EGFR in most common solid tumors is not inconsistent with
      the modest clinical activity observed in these single-agent trials. In addition,
      the lack of enrollment of patients with EGFR-dependent tumors onto these trials
      leaves open the possibility that these studies may have included some tumors that
      benefited from these therapies but for which this benefit was diluted and thus
      not detected within the enrolled patient population at large. These
      considerations suggest that the enrollment of unselected patients onto trials
      with EGFR inhibitors should be revisited to identify a cohort of EGFR-dependent
      tumors against which EGFR inhibitors might exhibit clinical activity. This
      approach would also exclude patients for whom these drugs will not induce any
      clinical benefit.

PMID- 14645417
TI  - Chemotherapy for teratoma with malignant transformation.
AB  - PURPOSE: Teratoma with malignant transformation (MT) is a well-described entity
      that refers to the MT of a somatic teratomatous component in a germ cell tumor
      (GCT) to a histology that is identical to a somatic malignancy (eg,
      rhabdomyosarcoma [RMS]). Surgical resection has been the mainstay of therapy for
      localized transformed disease because these tumors are thought to be resistant to
      standard treatment. We report that chemotherapy has a role in selected patients
      with MT, determined by cell type. PATIENTS AND METHODS: Chemotherapy was
      administered to 12 patients with MT of GCT limited to a single cell type (two
      patients with primitive neuroectodermal tumors, five with undifferentiated RMS,
      one with anaplastic small-cell tumor, two with adenocarcinoma, and two with
      leukemia); 10 patients had measurable disease. GCT origin was confirmed by
      molecular cytogenetics in five patients. Each patient received chemotherapy
      regimens based on the specific malignant cell observed in the transformed
      histology. RESULTS: Seven patients with measurable disease achieved a partial
      response, with the duration of response ranging between 1 month and 7 years.
      Three of those patients are alive. Three patients did not respond to treatment,
      and all of those patients died as a result of their disease. CONCLUSION:
      Chemotherapy for MT limited to a single cell type may result in major responses
      and long-term survival in selected patients. Local therapy after chemotherapy is
      an important component of treatment to achieve maximum response.

PMID- 14645418
TI  - Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate
      cancer: clinical trial results with alpha-N-acetylgalactosamine-O
      serine/threonine conjugate vaccine.
AB  - PURPOSE: We report the synthesis of a mucin-related O-linked glycopeptide, alpha
      N-acetylgalactosamine-O-serine/threonine (Tn), which is highly simplistic in its
      structure and can induce a relevant humoral response when given in a trimer or
      clustered (c) formation. We tested for an antitumor effect, in the form of a
      change in the posttreatment versus pretreatment prostate-specific antigen (PSA)
      slopes, that might serve as a surrogate for effectiveness of vaccines in delaying
      the time to radiographic progression. METHODS: We compared the antibody response
      to immunization with two conjugates, Tn(c)-keyhole limpet hemocyanin (KLH) and
      Tn(c)-palmitic acid (PAM) with the saponin immunologic adjuvant QS21, in a phase
      I clinical trial in patients with biochemically relapsed prostate cancer.
      Patients received Tn(c)-KLH vaccine containing either 3, 7, or 15 microg of Tn(c)
      per vaccination. Ten patients received 100 microg of Tn(c)-PAM. QS21 was included
      in all vaccines. Five vaccinations were administered subcutaneously during 26
      weeks with an additional booster vaccine at week 50. RESULTS: Tn(c), when given
      with the carrier molecule KLH and QS21, stimulated the production of high-titer
      immunoglobulin M (IgM) and IgG antibodies. Inferior antibody responses were seen
      with T(c)-PAM. There was no evidence of enhanced immunogenicity with increasing
      doses of vaccine. An antitumor effect in the form of a decline in posttreatment
      versus pretreatment PSA slopes was also observed. CONCLUSION: A safe synthetic
      conjugate vaccine in a trimer formation was developed that can break immunologic
      tolerance by inducing specific humoral responses. It seemed to affect the
      biochemical progression of the disease as determined by a change in PSA log
      slope.

PMID- 14645419
TI  - Minichromosome maintenance protein 2 is a strong independent prognostic marker in
      breast cancer.
AB  - PURPOSE: To test the hypothesis that prognostic information in breast cancer may
      be derived from an accurate assessment of epithelial cell cycle entry, as
      indicated by expression of minichromosome maintenance (MCM) proteins. MATERIALS
      AND METHODS: We used immunohistochemistry to examine the distribution of Mcm-2 in
      breast tissue. Power calculations based on a pilot study of 67 whole tissue
      sections led to selection of an independent 347-core breast carcinoma tissue
      microarray validation set. We tested for associations between Mcm-2 (and Ki-67)
      labeling index (LI) and various clinicopathologic parameters. RESULTS: Mcm-2 was
      expressed more frequently than the standard proliferation marker Ki-67 in whole
      tissue sections of normal breast (P =.0003) and breast carcinoma (P <.0001). In
      221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive
      association with tumor size (P =.002), mitotic index (P <.0001), histologic grade
      (P <.0001), and the Nottingham Prognostic Index (NPI) score (P <.0001). Using a
      cutoff value of 50%, Mcm-2 LI was associated with overall survival (P =.0007),
      disease-free interval (P =.0002), and with the development of regional recurrence
      (P =.011) and distant metastases (P =.0016). Cox regression analysis suggested
      that the Mcm-2 LI is a strong prognostic factor in breast cancer that is
      independent and superior to histologic grade, lymph node stage, and Ki-67 LI, but
      not the NPI score. CONCLUSION: Mcm-2 may be of utility as a prognostic marker to
      refine the prediction of outcome in breast cancer, for example when combined with
      parameters currently used in the NPI.

PMID- 14645420
TI  - Prognostic characteristics of breast cancer among postmenopausal hormone users in
      a screened population.
AB  - PURPOSE: We determined the risk of breast cancer and tumor characteristics among
      current postmenopausal hormone therapy users compared with nonusers, by duration
      of use. METHODS: From January 1996 to December 2000, data were collected
      prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent
      screening mammography. We calculated the relative risk (RR) of breast cancer
      (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months
      of postmenopausal therapy use among current hormone users with a uterus (proxy
      for estrogen and progestin use) and without a uterus (proxy for estrogen use),
      compared with nonusers. RESULTS: Compared with nonusers, women using estrogen and
      progestin for >/= 5 years were at increased risk of breast tumors of stage 0 or I
      (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to
      1.63), size </= 20 mm (RR, 1.59; 95% CI, 1.43 to 1.76), size greater than 20 mm
      (RR, 1.24; 95% CI, 1.09 to 1.42), grade 1 or 2 (RR, 1.60; 95% CI, 1.44 to 1.77),
      grade 3 or 4 (RR, 1.54; 95% CI, 1.37 to 1.73), and estrogen receptor-positive
      (RR, 1.72; 95% CI, 1.55 to 1.90). Estrogen-only users were slightly more likely
      to have estrogen receptor-positive breast cancer compared with nonusers (RR,
      1.14; 95% CI, 1.06 to 1.23). CONCLUSION: Use of estrogen and progestin
      postmenopausal hormone therapy for five years or more increased the likelihood of
      developing breast cancer, including both tumors with favorable prognostic
      features and tumors with unfavorable prognostic features.

PMID- 14645421
TI  - Tamoxifen as chemoprevention in BRCA1 and BRCA2 mutation carriers with breast
      cancer: a pilot survey of physicians.
AB  - PURPOSE: To assess physician recommendations about the use of tamoxifen in
      premenopausal BRCA1 and BRCA2 mutation carriers. METHODS: We mailed surveys to a
      stratified random sample of 1,286 physicians selected from the San Antonio Breast
      Cancer Symposium mailing list. Eligible participants were physicians whose
      practice consisted of >/= 10% breast cancer patients. Participants were asked to
      complete a three-part, 10-minute questionnaire. Demographics and responses to
      hypothetical patient vignettes were analyzed. RESULTS: Of potentially eligible
      participants, 27% responded to the survey, and 260 participants were included in
      the final analysis. Physicians did not distinguish between BRCA1 and BRCA2 status
      in making recommendations about tamoxifen to breast cancer patients; however, in
      an unaffected woman, they were more likely to recommend tamoxifen to a BRCA2
      mutation carrier than to a BRCA1 mutation carrier (73% v 57%; P <.0001). In newly
      diagnosed breast cancer patients, physicians were much more likely to recommend
      tamoxifen to an estrogen receptor (ER)-positive mutation carrier versus an ER
      negative carrier (94% v 27%; P <.0001). When the mutation carrier was diagnosed
      10 years ago, physicians were still much more likely to recommend tamoxifen if
      the tumor was ER-positive versus ER-negative (79% v 35%; P <.0001). CONCLUSION:
      Physicians' recommendations about tamoxifen use in mutation carriers with a
      history of breast cancer seem to be heavily dependent on ER status. This finding
      suggests that among mutation carriers, physicians are influenced by adjuvant
      treatment guidelines more so than the potential role that tamoxifen might play in
      the reduction of risk for contralateral breast cancer.

PMID- 14645422
TI  - Risk of second primary malignancy after esophagectomy for squamous cell carcinoma
      of the thoracic esophagus.
AB  - PURPOSE: To assess the risk of subsequent malignancies after esophagectomy for
      squamous cell carcinoma of the thoracic esophagus for the establishment of an
      adequate follow-up program. PATIENTS AND METHODS: We statistically analyzed
      clinical factors in 114 cases of second malignancy after esophagectomy that
      developed in 94 of 679 patients who underwent curative resection. The cancer
      incidence rates in the general population estimated by the Research Group for
      Population-Based Cancer Registration in Japan were used as standards for
      comparison. RESULTS: The 10-year cumulative risk of second malignancy was 34.5%,
      and the overall relative risk (RR) was 2.98 (95% CI, 2.41 to 3.65). The risk of
      head and neck cancer was markedly elevated (RR, 34.9; 95% CI, 24.3 to 48.6),
      followed by the risks of lung cancer (RR, 3.24; 95% CI, 1.89 to 5.19) and stomach
      cancer (RR, 2.00; 95% CI, 1.17 to 3.21). Multifactor analysis demonstrated that
      independent factors affecting the risk of subsequent malignancies were presence
      of other malignancies detected before esophagectomy and any of the following
      factors: masculine sex, alcohol consumption, and smoking. The 5-year survival
      rate after detection of subsequent malignancy was 45%. The outcome in patients
      with subsequent head and neck cancer was significantly less favorable as a result
      of difficulty in early detection. CONCLUSION: Patients had a remarkably high risk
      of subsequent cancer of the upper aerodigestive tract after esophagectomy, in
      particular, head and neck cancer. Minute postoperative surveillance is strongly
      recommended, especially in patients with a history of malignancies before
      esophagectomy. Early detection of second malignancies allowed less invasive
      treatment with favorable outcome.

PMID- 14645423
TI  - Kinase mutations and imatinib response in patients with metastatic
      gastrointestinal stromal tumor.
AB  - PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively
      activated mutant isoforms of KIT or kinase platelet-derived growth factor
      receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib
      mesylate. The relationship between mutations in these kinases and clinical
      response to imatinib was examined in a group of patients with advanced GIST.
      PATIENTS AND METHODS: GISTs from 127 patients enrolled onto a phase II clinical
      study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types
      were correlated with clinical outcome. RESULTS: Activating mutations of KIT or
      PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT
      mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms,
      but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in
      vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial
      response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9
      KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P
      =.0006) and 0.0% (P <.0001), respectively. Patients whose tumors contained exon
      11 KIT mutations had a longer event-free and overall survival than those whose
      tumors expressed either exon 9 KIT mutations or had no detectable kinase
      mutation. CONCLUSION: Activating mutations of KIT or PDGFRA are found in the vast
      majority of GISTs, and the mutational status of these oncoproteins is predictive
      of clinical response to imatinib. PDGFRA mutations can explain response and
      sensitivity to imatinib in some GISTs lacking KIT mutations.

PMID- 14645424
TI  - Adjuvant treatment for early ovarian cancer: a randomized phase III trial of
      intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a gynecologic
      oncology group study.
AB  - PURPOSE: To conduct a prospective study of intraperitoneal radioactive chromic
      phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early
      ovarian cancer at high risk for recurrence (International Federation of
      Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no
      macroscopic residual disease) and to compare cumulative incidence of recurrence,
      overall survival, and relative toxicity. MATERIALS AND METHODS: A total of 251
      patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%)
      were ineligible following centralized pathology review. Of the 229 patients
      included in the analysis, 110 received 32P, and 119 received CP. RESULTS: The
      cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for
      patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP.
      Patients receiving CP had a recurrence rate 29% lower than that of those
      receiving 32P (P =.15, two-tail test). The death rate for patients treated with
      CP was 17% lower than that for patients treated with 32P (difference not
      significant). Combining both arms, the 10-year cumulative incidence of recurrence
      for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI,
      32% to 56%) for stage II patients (P =.01). Both regimens were reasonably well
      tolerated, but problems with inadequate distribution (7%) and small-bowel
      perforation (3%) make the otherwise less toxic 32P less acceptable. CONCLUSION:
      Although there are no statistically significant differences in survival, the
      lower cumulative recurrence seen with CP and complications of 32P administration
      make platinum-based combinations the preferred adjuvant therapy for early ovarian
      cancer patients at high-risk for recurrence.

PMID- 14645425
TI  - Phase II trial of carboxyamidotriazole in patients with relapsed epithelial
      ovarian cancer.
AB  - PURPOSE: Carboxyamidotriazole (CAI) is a cytostatic inhibitor of nonvoltage
      operated calcium channels and calcium channel-mediated signaling pathways. It
      inhibits angiogenesis, tumor growth, invasion, and metastasis. We hypothesized
      that CAI would promote disease stabilization lasting >/= 6 months in patients
      with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with epithelial
      ovarian cancer, good end-organ function, measurable disease, and three or fewer
      prior regimens were eligible. Oral CAI was given daily using a pharmacokinetic
      dosing approach to maintain plasma concentrations between 2 and 4 microg/mL.
      Radiographic imaging to assess response was performed every 8 weeks. Positive
      outcome included stabilization or improvement of disease lasting >/= 6 months.
      Plasma vascular endothelial growth factor (VEGF), interleukin (IL)-8, and matrix
      metalloproteinase (MMP)-2 were measured. RESULTS: Thirty-six patients were
      assessable for primary end point analysis, and 38 were assessable for toxicity.
      Forty-four percent of patients had three prior regimens, more than 50% had four
      or more disease sites, and 48% had liver metastases. Thirty-three patients
      reached the targeted concentration range during the first cycle. Eleven patients
      (31%) attained the >/= 6-month outcome end point, with one partial response (8
      months) and three minor responses (8, 12+, and 13 months). Median time to
      progression was 3.6 months (range, 1.6 to 13.3 months). CAI was well tolerated,
      with mostly grade 1 to 2 toxicity. Grade 3 events included fatigue (5%), vomiting
      (2%), neutropenic fever (2%), and neutropenia (2%). There were no grade 4 adverse
      events. No associations between VEGF, IL-8, and MMP-2 with CAI concentration or
      clinical outcome were observed. CONCLUSION: CAI is a potential agent for
      additional study in the stabilization of relapsed ovarian cancer. Given a limited
      toxicity profile, it may have utility as a maintenance therapeutic agent for this
      disease.

PMID- 14645426
TI  - Toward new strategies to select young endometrial cancer patients for mismatch
      repair gene mutation analysis.
AB  - PURPOSE: To determine the frequency of mismatch repair (MMR) gene germline
      mutations in endometrial cancer patients who were diagnosed at less than 50 years
      of age; to relate the presence of mutations to family history, histopathologic
      data, presence of tumor microsatellite instability (MSI), and immunostaining; and
      to formulate criteria for genetic testing in these patients. PATIENTS AND
      METHODS: Endometrial cancer patients (N = 58), who were diagnosed at less than 50
      years of age, were included and questioned about their family history. Mutation
      analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel
      electrophoresis and sequence analysis to detect small mutations and multiplex
      ligation-dependent probe amplification to detect large deletions or
      duplications). For MSI analysis, five consensus markers were used, and
      immunostaining of the three MMR proteins was performed. RESULTS: In five of 22
      patients with a positive first-degree family history for hereditary nonpolyposis
      colorectal cancer (HNPCC)-related cancers, pathogenic germline mutations were
      found (one MLH1, three MSH2, and one MSH6). Four mutation carriers belonged to
      families fulfilling the revised Amsterdam criteria. No mutations were found in
      the 35 patients without such family history (P =.006). MSI was detected in 20 of
      57 cancers, among which four were from mutation carriers. In 23 of 51 cancers,
      one or more MMR protein was absent; in all five mutation carriers, immunostaining
      indicated the involved MMR gene. CONCLUSION: In 23% of the young endometrial
      cancer patients with at least one first-degree relative with an HNPCC-related
      cancer, an MMR gene mutation was detected. Therefore, presence of an HNPCC
      related cancer in a first-degree relative seems to be an important selection
      criterion for mutation analysis. Subsequent immunostaining of MMR proteins will
      point to the gene(s) that should be analyzed.

PMID- 14645427
TI  - High-risk Merkel cell carcinoma of the skin treated with synchronous
      carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group
      Study--TROG 96:07.
AB  - PURPOSE: The effectiveness of synchronous carboplatin, etoposide, and radiation
      therapy was prospectively assessed in a group of patients with high-risk Merkel
      cell carcinoma (MCC) of the skin. PATIENTS AND METHODS: Patients were eligible if
      they had disease localized to the primary site and nodes, and were required to
      have at least one of the following high risk features: recurrence after initial
      therapy, involved nodes, primary tumor size greater than 1 cm, gross residual
      disease after surgery, or occult primary with nodes. Radiation was delivered to
      the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and
      synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80
      mg/m2 days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group
      was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved
      nodes (stage II) were present in 33 cases (62%). The sites involved were head and
      neck (22 patients), occult primary (13 patients), upper limb (eight patients),
      lower limb (eight patients), and trunk (two patients). RESULTS: Fifty-three
      patients were entered between 1996 and 2001. The median potential follow-up was
      48 months. There were no treatment related deaths. The 3-year overall survival,
      locoregional control, and distant control were 76%, 75%, and 76%, respectively.
      Tumor site and the presence of nodes were factors that were predictive for local
      control and survival. Multivariate analysis indicated that the major factor
      influencing survival was the presence of nodes; however, this was not a
      significant factor in locoregional control. CONCLUSION: High levels of
      locoregional control and survival have been achieved with the addition of
      chemotherapy to radiation treatment for high-risk MCC of the skin. The role of
      chemoradiotherapy for high-risk MCC warrants further investigation.

PMID- 14645428
TI  - Outcome in children with relapsed acute myeloid leukemia after initial treatment
      with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the
      French Society of Pediatric Hematology and Immunology.
AB  - PURPOSE: After present first-line therapies for childhood acute myeloid leukemia
      (AML), nearly 40% of patients still relapse. The goals of this retrospective
      study were to determine whether these children could be treated successfully with
      a salvage regimen and to establish the optimal therapeutic strategy. PATIENTS AND
      METHODS: In the multicentric, prospective, Leucemie Aique Myeloide Enfant 89/91
      protocol, 106 of the 308 children enrolled between 1988 and 1998 relapsed.
      Initial treatment after the first complete remission (CR1) had been allogenic HLA
      identical bone marrow transplantation (BMT; n = 21) or chemotherapy (n = 85).
      Treatment procedures were scheduled according to the choice of each participating
      institution. RESULTS: When reinduction therapy was attempted, second complete
      remission (CR2) was obtained in 71% of patients (68 of 96 patients). BMT was
      performed in 53 (78%) of these 68 patients (autograft, mainly harvested in CR1, n
      = 25; matched sibling-donor BMT, n = 12; or alternative-donor BMT, n = 16). The 5
      year overall survival (OS) rate for all 106 patients was 33%, and the disease
      free survival (DFS) rate for children in CR2 was 45%. Multivariate analysis of re
      treated children showed that the 5-year OS was higher if the CR1 had been longer
      than 12 months compared with less than 12 months (54% v 24%, respectively; P
      =.001) and lower if maintenance therapy had been given after CR1 compared with
      chemotherapy without maintenance therapy or HLA-identical BMT (12% v 40% v 52%,
      respectively; P =.002). For patients attaining CR2, the 5-year DFS rate was not
      significantly different for matched sibling-donor BMT (60%), autograft (47%), or
      alternative-donor BMT (44%). CONCLUSION: After aggressive first-line therapy, one
      third of unselected, relapsing AML children could be cured. Further prospective
      trials are warranted to define the optimal reinduction regimen and megadose
      chemotherapy and to evaluate the late effects of these therapies.

PMID- 14645429
TI  - High risk of subsequent neoplasms continues with extended follow-up of childhood
      Hodgkin's disease: report from the Late Effects Study Group.
AB  - PURPOSE: We present an update of a previously reported Late Effects Study Group
      cohort of 1,380 children with Hodgkin's disease (HD) diagnosed between 1955 and
      1986 in patients aged 16 years or younger. We describe the pattern and incidence
      of subsequent neoplasms (SNs) occurring with extended follow-up. PATIENTS AND
      METHODS: Median age at diagnosis of HD was 11.7 years (range, 0.3 to 16.9 years)
      and at last follow-up was 27.8 years. Median length of follow-up was 17.0 years.
      RESULTS: An additional 103 SNs were ascertained (total SNs = 212). The cohort was
      at an 18.5-fold increased risk of developing SNs compared with the general
      population (standardized incidence ratio [SIR], 18.5, 95% CI, 15.6 to 21.7). The
      cumulative incidence of any second malignancy was 10.6% at 20 years, increasing
      to 26.3% at 30 years; and of solid malignancies was 7.3% at 20 years, increasing
      to 23.5% at 30 years. Breast cancer was the most common solid malignancy (SIR,
      56.7). Other commonly occurring solid malignancies included thyroid cancer (SIR,
      36.4), bone tumors (SIR, 37.1), and colorectal (SIR, 36.4), lung (SIR, 27.3), and
      gastric cancers (SIR, 63.9). Risk factors for solid tumors included young age at
      HD and radiation-based therapy. Thirty-two patients developed third neoplasms,
      with the cumulative incidence approaching 21% at 10 years from diagnosis of
      second malignancy. CONCLUSION: Additional follow-up of this large cohort of HD
      survivors documents an increasing occurrence of known radiation-associated solid
      tumors, (breast and thyroid cancers), as well as emergence of epithelial
      neoplasms common in adults, (colon and lung cancers) at a younger age than
      expected in the general population, necessitating ongoing surveillance of this
      high risk population.

PMID- 14645430
TI  - Impact of CNS treatment on mood in adult survivors of childhood leukemia: a
      report from the Children's Cancer Group.
AB  - PURPOSE: This study assessed the relationship between CNS treatment and
      psychologic mood using the Profile of Moods State (POMS), a standardized measure
      of affect, among a large sample of young adult survivors of childhood acute
      lymphoblastic leukemia (ALL; N = 555). PATIENTS AND METHODS: Survivors of
      childhood ALL (ages 18 to 33 years at study entry) participated in a structured
      telephone interview eliciting demographic, health, and behavioral data and the
      POMS. Treatment data included total dose of CNS irradiation (CRT) and intrathecal
      methotrexate (MTX) obtained from medical records. RESULTS: Mood disturbance was
      reported by 24% of survivors. High-dose CRT and MTX predicted disturbance rates
      modestly and primarily in combination with education variables. Interactions
      between educational achievement, a history of attendance in special education
      classes, and sex were better predictors than treatment type or dose. Nonwhite
      males, those younger than 12.5 years of age at diagnosis, and those with negative
      perceptions of current health and cancer's impact on employment were also at
      greater risk for mood disturbance (P <.01 to.001). CONCLUSION: Although most
      survivors are doing well psychologically, a subset of long-term survivors show
      potentially serious mood disturbance. Mood disturbance seems to be a function of
      interactions between preexisting individual difference variables (eg, sex,
      race/ethnicity), treatment factors, and posttreatment educational experiences.
      Prevention strategies aimed at childhood cancer survivors at greatest risk for
      mood disturbance may be improved by focus on posttreatment psychosocial and
      educational supports.

PMID- 14645431
TI  - Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle
      cell lymphoma.
AB  - PURPOSE: Patients with relapsed mantle-cell lymphoma have poor prognosis and
      short survival. Our aim was to determine the efficacy of nonablative allogeneic
      stem-cell transplantation in patients with relapsed mantle-cell lymphoma.
      PATIENTS AND METHODS: Eighteen patients were treated in one of two consecutive
      trials. Thirteen patients underwent a conditioning regimen of fludarabine (30
      mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high
      dose rituximab. For the remaining five patients, the conditioning regimen
      consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily
      for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and
      methotrexate were used for graft-versus-host disease prophylaxis. RESULTS: The
      median age was 56.5 years. Patients underwent a median of three prior
      chemotherapy regimens. Prior autologous transplantation failed in five (28%)
      patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred
      in all patients. Eight patients (44%) required no platelet or RBC transfusion,
      and acute graft-versus-host disease of greater than grade 2 did not develop in
      any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17
      patients. Three patients progressed, and one was reinduced into continuous CR
      with donor lymphocyte infusion. With a median follow-up period of 26 months, the
      actuarial probability of current-event-free-survival at 3 years was 82% (95% CI,
      65% to 99%). CONCLUSION: Our data suggest that nonablative allogeneic
      transplantation is a safe and potentially effective strategy for patients with
      relapsed and chemosensitive mantle-cell lymphoma.

PMID- 14645432
TI  - Prognostic value of minimal residual disease quantification by real-time reverse
      transcriptase polymerase chain reaction in patients with core binding factor
      leukemias.
AB  - PURPOSE: In patients with acute myeloblastic leukemia with t(8;21) or inv(16)
      aberrations (core binding factor [CBF] leukemias), minimal residual disease (MRD)
      can be sensitively detected during and after chemotherapy by use of molecular
      methods. However, the prognostic impact of qualitative MRD detection is still
      under debate. In this study, the prognostic value of MRD quantification in
      patients with CBF leukemias was assessed. PATIENTS AND METHODS: We quantified MRD
      at various time points during and after therapy by real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) for AML1/MTG8 and CBFB/MYH11 in
      37 patients with CBF leukemias treated within a multicenter trial. RESULTS: At
      initial diagnosis, the patients showed a heterogenous fusion gene expression
      relative to glyceraldehyde 3-phosphate dehydrogenase with a variation of more
      than two log steps. According to MRD status during/after therapy, two groups of
      patients were separated. Of the 26 patients who had MRD levels of less than 1% in
      relation to initial diagnosis at all time points tested after induction
      chemotherapy, only two experienced relapse after a median follow-up of 19 months.
      Of the 11 patients who had a sample with an MRD level >/= 1% at least at one time
      point after induction therapy, 10 experienced relapse, with a median remission
      duration of 10 months (P <.001). The median interval between the informative MRD
      sample and clinical relapse in these patients was 3 months. CONCLUSION: MRD
      quantification by real-time RT-PCR allows the identification of patients with a
      high risk of relapse among the CBF leukemias.

PMID- 14645433
TI  - Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day
      schedule to patients with cancer: magnetic resonance imaging evidence for altered
      tumor blood flow.
AB  - PURPOSE: Combretastatin A4 (CA4) phosphate (CA4P) inhibits microtubule
      polymerization and is toxic to proliferating endothelial cells in vitro. It
      causes reversible vascular shutdown in established tumors in vivo, consistent
      with an antivascular mechanism of action. The present study investigated
      escalating doses of CA4P administered intravenously to patients with advanced
      cancer. PATIENTS AND METHODS: Patients with solid malignancies and good
      performance status received CA4P as a 10-minute infusion daily for 5 days
      repeated every 3 weeks. Pharmacokinetic sampling was performed during cycle 1.
      Patients receiving >/= 52 mg/m2/d had serial dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) studies to measure changes in tumor perfusion with
      CA4P treatment. RESULTS: Thirty-seven patients received 133 treatment cycles.
      CA4P dose levels ranged from 6 mg/m2 to 75 mg/m2 daily. Severe pain at sites of
      known tumor was dose limiting at 75 mg/m2. Dose-limiting cardiopulmonary toxicity
      (syncope and dyspnea or hypoxia) was noted as well in two patients treated at 75
      mg/m2. Other toxicities included hypotension, ataxia, dyspnea, nausea or
      vomiting, headache, and transient sensory neuropathy. Plasma CA4P and CA4 area
      under the concentration-time curve and maximal concentration values increased
      linearly with dose. Tumor perfusion, as measured by the first-order rate constant
      of gadolinium plasma to tissue transfer during DCE-MRI studies, was found to
      decrease in eight of 10 patients. Relationships were also demonstrated between
      perfusion changes and pharmacokinetic indices. A partial response was observed in
      a patient with metastatic soft tissue sarcoma, and 14 patients exhibited disease
      stability for a minimum of two cycles. CONCLUSION: Doses of CA4P on a daily times
      five schedule of 52 to 65 mg/m2 were reasonably well-tolerated. The 52 mg/m2 dose
      is recommended for further study based on cumulative phase I experience with
      CA4P. Antitumor efficacy was observed, and the use of DCE-MRI provided a valuable
      noninvasive measure of the vascular effects of CA4P treatment.

PMID- 14645434
TI  - Patient-controlled methylphenidate for the management of fatigue in patients with
      advanced cancer: a preliminary report.
AB  - PURPOSE: To assess the effects of patient-controlled methylphenidate for cancer
      related fatigue. PATIENTS AND METHODS: In this prospective open study, 31
      patients with advanced cancer and fatigue who scored >/= 4 on a scale of 0 to 10
      received methylphenidate 5 mg by mouth every 2 hours as needed for 7 days
      (maximum, 20 mg/d). Multiple symptoms were assessed daily; the primary end point,
      fatigue, was measured using the 0 to 10 scale, and the Functional Assessment for
      Chronic Illness Therapy-Fatigue (FACIT-F) was performed at baseline, day 7, and
      day 28. RESULTS: The following mean (+/- standard deviation) scores for 30
      assessable patients improved significantly between baseline and day 7: fatigue (0
      to 10 scale), 7.2 +/- 1.6 v 3.0 +/- 1.9 (P <.001); overall well-being (0 to 10
      scale), 4.5 +/- 2.2 v 2.8 +/- 2.1 (P <.001); fatigue (FACIT-F) subscore, 17.5 +/-
      11.3 v 34.7 +/- 10.0 (P <.001); functional well-being, 14.4 +/- 5.9 v 18.3 +/-
      6.6 (P <.001); and physical well-being, 13.5 +/- 6.4 v 21.4 +/- 5.0 (P <.001).
      Anxiety, appetite, pain, nausea, depression, and drowsiness all improved
      significantly (P <.05). All patients took afternoon or evening doses, and 28
      patients (93%) took three or more doses daily. All patients chose to continue
      taking methylphenidate after 7 days of treatment. No serious side effects were
      reported. CONCLUSION: These preliminary results suggest that patient-controlled
      methylphenidate administration rapidly improved fatigue and other symptoms.
      Randomized controlled trials are justified.

PMID- 14645435
TI  - Treatment of plasma cell dyscrasias with thalidomide and its derivatives.
AB  - PURPOSE: In 1999, investigators reported promising results of a phase II study of
      thalidomide in patients with resistant multiple myeloma (MM). Since then, various
      trials of thalidomide alone and in combination with other agents have been tested
      in patients with resistant and, more recently, untreated MM. In addition,
      preliminary results of phase I studies of the immunomodulatory derivatives
      (IMiDs) of thalidomide have been recently reported. DESIGN: We reviewed and
      report the results of clinical trials of thalidomide and the IMiDs, as well as
      the pharmacology, mechanism of action, and toxicity of these agents. RESULTS:
      Thalidomide has demonstrated significant activity in both resistant and
      previously untreated multiple myeloma. Combination therapy with dexamethasone
      increases response rate, even in patients previously resistant to both drugs
      given as single agents. More recent studies of thalidomide with dexamethasone in
      previously untreated patients are highly encouraging. The addition of
      chemotherapy to thalidomide and dexamethasone may further increase response
      rates, but its effect on patient survival has not been clarified. Preliminary
      results of trials of IMiD-3 indicate that this agent is active in resistant
      myeloma and has a toxicity profile different from that of thalidomide.
      CONCLUSION: Many studies have confirmed the activity of thalidomide in MM, as
      well as an improved response with dexamethasone. Newer thalidomide derivatives
      with reduced toxicity (neuropathy, teratogenicity) are also promising.
      Thalidomide with dexamethasone may now represent the treatment of choice for
      previously untreated patients. Further studies with these and other novel agents
      early in the course of myeloma may improve complete remission rates and frequency
      of long-term control.

PMID- 14645436
TI  - Common malignancies with uncommon sites of presentation: case 1. Anterior
      mediastinal rhabdomyosarcoma.

PMID- 14645437
TI  - Common malignancies with uncommon sites of presentation: case 2. Mantle-cell
      lymphoma of the prostate.

PMID- 14645438
TI  - Common malignancies with uncommon sites of presentation: case 3. Epigastric
      distress caused by a duodenal polyp: a rare presentation of acute leukemia.

PMID- 14645439
TI  - Spirituality and religion in the "art of dying".

PMID- 14645441
TI  - Importance of minimal residual disease testing during the second year of disease:
      still no answer?

PMID- 14645442
TI  - When the tumor is not the target: a title whose time is up?

PMID- 14645445
TI  - Benefit of Paclitaxel in estrogen receptor-negative versus estrogen receptor
      positive early breast cancer.

PMID- 14645446
TI  - Carcinoembryonic antigen surge in metastatic colorectal cancer patients
      responding to oxaliplatin combination chemotherapy: implications for tumor marker
      monitoring and guidelines.

PMID- 14645447
TI  - Staging reclassification affects breast cancer survival.

PMID- 14645448
TI  - Ca(2+) and frequency dependence of exocytosis in isolated somata of magnocellular
      supraoptic neurones of the rat hypothalamus.
AB  - In addition to action potential-evoked exocytotic release at neurohypophysial
      nerve terminals, the neurohormones arginine vasopressin (aVP) and oxytocin (OT)
      undergo Ca(2+)-dependent somatodendritic release within the supraoptic and
      paraventricular hypothalamic nuclei. However, the cellular and molecular
      mechanisms that underlie this release have not been elucidated. In the present
      study, the whole-cell patch-clamp technique was utilized in combination with high
      time-resolved measurements of membrane capacitance (C(m)) and microfluorometric
      measurements of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) to examine the
      Ca(2+) and stimulus dependence of exocytosis in the somata of magnocellular
      neurosecretory cells (MNCs) isolated from rat supraoptic nucleus (SON). Single
      depolarizing steps (> or =20 ms) that evoked high-voltage-activated (HVA) Ca(2+)
      currents (I(Ca)) and elevations in intracellular Ca(2+) concentration were
      accompanied by an increase in C(m) in a majority (40/47) of SON neurones. The
      C(m) responses were composed of an initial Ca(2+)-independent, transient
      component and a subsequent, sustained phase of increased C(m) (termed DeltaC(m))
      mediated by an influx of Ca(2+), and increased with corresponding prolongation of
      depolarizing step durations (20-200 ms). From this relationship we estimated the
      rate of vesicular release to be 1533 vesicles s(-1). Delivery of neurone-derived
      action potential waveforms (APWs) as stimulus templates elicited I(Ca) and also
      induced a DeltaC(m), provided APWs were applied in trains of greater than 13 Hz.
      A train of APWs modelled after the bursting pattern recorded from an OT
      containing neurone during the milk ejection reflex was effective in supporting an
      exocytotic DeltaC(m) in isolated MNCs, indicating that the somata of SON neurones
      respond to physiological patterns of neuronal activity with Ca(2+)-dependent
      exocytotic activity.

PMID- 14645449
TI  - The cerebral oscillatory network of voluntary tremor.
AB  - It has recently been shown that resting tremor in Parkinson's disease is
      associated with oscillatory neural coupling in an extensive cerebral network
      comprising a cerebello-diencephalic-cortical loop and cortical motor,
      somatosensory and posterior parietal areas contralateral to the tremor hand. The
      aim of the present study was to investigate whether this oscillatory brain
      network exclusively reflects a pathophysiological state in parkinsonian resting
      tremor or whether it constitutes a fundamental feature of physiological motor
      control. We investigated cerebro-muscular and cerebro-cerebral coupling in 11
      healthy subjects imitating typical antagonistic parkinsonian tremor. We recorded
      brain activity with a 122-channel whole-head neuromagnetometer and surface EMGs
      of the forearm extensor. Analysis of cerebro-muscular and cerebro-cerebral
      coherence revealed oscillatory coupling in the same brain structures that
      comprise the oscillatory network of parkinsonian resting tremor. Interestingly,
      similar to parkinsonian resting tremor, cerebro-cerebral coherences often showed
      a significant peak at twice the simulated tremor frequency. The most striking
      differences between parkinsonian patients, as investigated in a previous study
      and healthy subjects imitating the antagonistic resting tremor were a reduction
      of the coupling between primary sensorimotor cortex and a diencephalic structure-
      most likely the thalamus--and an enhancement of the coupling between premotor and
      primary sensorimotor cortex. Our results indicate that the coupling of
      oscillatory activity within a cerebello-diencephalic-cortical loop constitutes a
      basic feature of physiological motor control. Thus, our data are consistent with
      the hypothesis that parkinsonian resting tremor involves oscillatory cerebro
      cerebral coupling in a physiologically pre-existing network.

PMID- 14645450
TI  - The impact of splice isoforms on voltage-gated calcium channel alpha1 subunits.
AB  - Semi-conserved exon boundaries in members of the CACNA1 gene family result in
      recurring pre-mRNA splicing patterns. The resulting variations in the encoded
      pore-forming subunit of the voltage-gated calcium channel affect functionally
      significant regions, such as the vicinity of the voltage-sensing S4 segments or
      the intracellular loops that are important for protein interaction. In addition
      to generating functional diversity, RNA splicing regulates the quantitative
      expression of other splice isoforms of the same gene by producing transcripts
      with premature stop codons which encode two-domain or three-domain channels. An
      overview of some of the known splice isoforms of the alpha(1) calcium channel
      subunits and their significance is given.

PMID- 14645452
TI  - Structure and function of AMPA receptors.
AB  - The application of X-ray diffraction has allowed the structure of the ligand
      binding core of AMPA receptors to be determined. Here I review the insights that
      this has given into the molecular mechanisms of activation and desensitization of
      these receptors.

PMID- 14645451
TI  - Fatigue-related depression of the feline monosynaptic gastrocnemius-soleus
      reflex.
AB  - In decerebrate cats, changes in the monosynaptic reflex (MSR) of gastrocnemius
      soleus (G-S) motoneurones were studied after fatiguing stimulation (FST) of the G
      S muscles. Monosynaptic reflexes were evoked by stimulation of Ia fibres in the G
      S nerve and recorded from a filament of ventral root (VR) L7. FST (intermittent
      40 s(-1) stimulation for 10-12 min) was applied to the distal part of the cut VR
      S1. FST reduced MSR amplitudes to 0.64 +/- 0.04 (mean +/-s.e.m.) of the
      prefatigue values. The suppression remained stable for approximately 25 min and
      then MSR amplitudes gradually returned towards the normal. To test for the
      involvement of presynaptic and recurrent inhibition, MSRs were conditioned by
      stimulation of the nerve to the posterior biceps and semitendinosus (PBSt)
      muscles or a filament of VR L7, respectively. The intensity of presynaptic
      inhibition (reduction of the normalized value of MSR amplitude during
      conditioning) increased from 0.19 +/- 0.02 in prefatigue to 0.44 +/- 0.04 within
      a 5.3-18.2 min interval after FST, followed by a recovery. In contrast, the
      intensity of recurrent inhibition first diminished from 0.23 +/- 0.02 in
      prefatigue to 0.15 +/- 0.01 within 15.6-30.1 min after FST and then gradually
      recovered. Both primary afferent depolarization and the intensity of antidromic
      discharges in primary afferents increased with the presynaptic inhibition
      intensity. These results demonstrate a fatigue-related suppression of Ia
      excitation of synergistic motoneurones, probably arising from the activation of
      group III and IV afferents. The effects could in part be due to increased
      presynaptic inhibition, while recurrent inhibition plays a minor role.

PMID- 14645453
TI  - Effects of interactions between interleukin-1 beta and leptin on cat intestinal
      vagal mechanoreceptors.
AB  - In a previous study, we established that leptin acts on chemosensitive intestinal
      vagal mechanoreceptors and that its excitatory effects are blocked by the
      endogenous interleukin-1beta receptor antagonist (Il-1ra). To determine how
      interleukin-1beta (Il-1beta) is involved in the action of leptin, we studied the
      effects of this drug on the single vagal afferent activities of intestinal
      mechanoreceptors in anaesthetized cats. For this purpose, the activity of 34
      intestinal vagal mechanoreceptors was recorded via glass microelectrodes
      implanted in the nodose ganglion. Il-1beta (1 microg) administered into the
      artery irrigating the upper part of the intestine activated both the 16 leptin
      activated units (type 1 units; P < 0.01) and the 12 leptin-inhibited units (type
      2 units; P < 0.001), but had no effect on the six leptin-insensitive units.
      Cholecystokinin (CCK, 10 microg) induced an activatory response only in the two
      types of Il-1beta-sensitive units. When Il-1beta was administered after CCK, its
      excitatory effects on type 1 units were enhanced, whereas the excitatory effects
      on type 2 units were abolished. Pre-treatment with Il-1ra (250 microg) blocked
      all the effects of Il-1beta and the excitatory effects of leptin on type 1 units,
      whereas it enhanced the inhibitory effects of leptin on type 2 units. It can
      therefore be concluded that (i) leptin acts on intestinal vagal mechanoreceptors
      via Il-1beta in the case of the type 1 units and independently of Il-1beta in the
      case of the type 2 units, and (ii) type 1 and type 2 units belong to two
      different populations of vagal afferents that transmit different information
      about ingestion or inflammation to the CNS, depending on the chemical
      environment.

PMID- 14645454
TI  - Mice overexpressing the cardiac sodium-calcium exchanger: defects in excitation
      contraction coupling.
AB  - Homozygous overexpression of the cardiac Na(+)-Ca(2+) exchanger causes cardiac
      hypertrophy and increases susceptibility to heart failure in response to stress.
      We studied the functional effects of homozygous overexpression of the exchanger
      at the cellular level in isolated mouse ventricular myocytes. Compared with patch
      clamped myocytes from wild-type animals, non-failing myocytes from homozygous
      transgenic mice exhibited increased cell capacitance (from 208 +/- 16 pF to 260
      +/- 15 pF, P < 0.05). Intracellular Ca(2+) oscillations were readily elicited in
      homozygous transgenic animals during depolarizations to +80 mV, consistent with
      rapid Ca(2+) overload caused by reverse Na(+)-Ca(2+) exchange. After
      normalization to cell capacitance, transgenic myocytes had significant increases
      in Na(+)-Ca(2+) exchange activity (318%) and peak L-type Ca(2+) current (8.2 +/-
      0.7 pA pF(-1) at 0 mV test potential) compared to wild-type (5.8 +/- 0.9 pA pF(
      1) at 0 mV, P < 0.02). The peak Ca(2+) current amplitude and its rate of
      inactivation could be modulated by rapid reversible block of the exchanger. Thus,
      we describe an unexpected direct influence of Na(+)-Ca(2+) exchange activity on
      the L-type Ca(2+) channel. Despite intact sarcoplasmic reticular Ca(2+) content
      and larger peak L-type Ca(2+) currents, homozygous transgenic animals exhibited
      smaller Ca(2+) transients (Delta[Ca(2+)](i)= 466 +/- 48 nm in transgenics versus
      892 +/- 104 nm in wild-type, P < 0.0005) and substantially reduced gain of
      excitation-contraction coupling. These alterations in excitation-contraction
      coupling may underlie the tendency for these animals to develop heart failure
      following haemodynamic stress.

PMID- 14645455
TI  - Selective antagonism of rat inhibitory glycine receptor subunits.
AB  - Retinal ganglion cells exhibit fast and slow inhibitory synaptic glycine currents
      that can be selectively inhibited by strychnine and 5,7-dichlorokynurenic acid
      (DCKA), respectively. In this study we examined whether strychnine and DCKA
      selectivity correlated with the subunit composition of the glycine receptor.
      Homomeric alpha1, alpha2 or alpha2* glycine subunits were in vitro expressed in
      human embryonic kidney cells (HEK 293). In cells expressing the alpha1 subunit,
      responses to 200 microm glycine were blocked by 1 microm strychnine but not by
      500 microm DCKA. In cells expressing the alpha2 subunit, both 1 microm strychnine
      and 500 microm DCKA were effective antagonists of 200 microm glycine. In cells
      expressing alpha2* subunits, which are much less glycine-sensitive, 10 mm glycine
      was inhibited by 500 microm DCKA but not by 1 microm strychnine. A single amino
      acid mutation in the alpha1 subunit (R196G), converted this subunit from DCKA
      insensitive to DCKA-sensitive. In conclusion, the comparative effectiveness of
      strychnine and DCKA can be used to distinguish between the alpha1, alpha2 and
      alpha2* receptor responses. Furthermore, a single amino acid near the glycine
      receptor's putative agonist binding site may account for differences in DCKA
      sensitivity amongst the alpha subunits.

PMID- 14645456
TI  - Group II metabotropic glutamate receptors enhance NMDA receptor currents via a
      protein kinase C-dependent mechanism in pyramidal neurones of rat prefrontal
      cortex.
AB  - The action of glutamate in CNS is mediated by the activation of metabotropic and
      ionotropic receptors. The metabotropic glutamate receptors (mGluRs) are highly
      enriched in prefrontal cortex (PFC) - a brain region critically involved in the
      regulation of cognition and emotion. Emerging evidence has suggested that mGluRs
      are viable drug targets for neuropsychiatric disorders associated with PFC
      dysfunction. However, the mGluR-mediated signalling in PFC remains unclear. To
      understand the physiological functions of postsynaptic group II mGluRs (mGluR2/3)
      in PFC neurones, we investigated the molecular and cellular mechanisms underlying
      the regulation of NMDA receptor channels by group II mGluRs. We found that APDC,
      a highly selective and potent group II mGluR agonist, reversibly increased NMDAR
      currents in acutely dissociated PFC pyramidal neurones. Selective group II mGluR
      antagonists, but not group I mGluR antagonists, blocked APDC-induced enhancement
      of NMDAR currents, suggesting the mediation by mGluR2/3 receptors. The APDC
      effect on NMDAR currents was independent of Mg(2+) block or membrane voltages,
      and primarily targeted NR2A subunits containing NMDARs. While changing protein
      kinase A levels was without effect, inhibiting protein kinase C (PKC) or dialysis
      with Ca(2+) chelators largely blocked the mGluR2/3 modulation of NMDAR currents.
      In contrast, inhibiting protein tyrosine kinases, cyclin-dependent kinase 5,
      Ca(2+)/calmodulin-dependent kinase II or the Ca(2+)/calmodulin-dependent
      phosphatase calcineurin failed to do so. Moreover, treatment of PFC slices with
      APDC significantly increased the PKC activity and PKC phosphorylation of NMDA
      receptors. These findings suggest that activation of mGluR2/3 receptors
      potentiates NMDAR channel functions in PFC through a PKC-dependent mechanism.
      This modulation may be relevant for developing novel mGluR-related
      pharmacological agents for the treatment of mental illnesses.

PMID- 14645459
TI  - Principles of neurological rehabilitation.

PMID- 14645457
TI  - Sensitivity limits for voltage control of P2Y receptor-evoked Ca2+ mobilization
      in the rat megakaryocyte.
AB  - G-protein-coupled receptor signalling has been suggested to be voltage dependent
      in a number of cell types; however, the limits of sensitivity of this potentially
      important phenomenon are unknown. Using the non-excitable rat megakaryocyte as a
      model system, we now show that P2Y receptor-evoked Ca2+ mobilization is
      controlled by membrane voltage in a graded and bipolar manner without evidence
      for a discrete threshold potential. Throughout the range of potentials studied,
      the peak increase in intracellular Ca2+ concentration ([Ca2+]i) in response to
      depolarization was always larger than the maximal reduction in [Ca2+]i following
      an equivalent amplitude hyperpolarization. Significant [Ca2+]i increases were
      observed in response to small amplitude (< 5 mV, 5 s duration) or short duration
      (25 ms, 135 mV) depolarizations. Individual cardiac action potential waveforms
      were also able to repeatedly potentiate P2Y receptor-evoked Ca2+ release and the
      response to trains of normally paced stimuli fused to generate prolonged [Ca2+]i
      increases. Furthermore, elevation of the temperature to physiological levels (36
      degrees C) resulted in a more sustained depolarization-evoked Ca2+ increase
      compared with more transient or oscillatory responses at 20-24 degrees C. The
      ability of signalling via a G-protein-coupled receptor to be potentiated by
      action potential waveforms and small amplitude depolarizations has broad
      implications in excitable and non-excitable tissues.

PMID- 14645460
TI  - Multidisciplinary approaches in progressive neurological disease: can we do
      better?

PMID- 14645461
TI  - Aids, orthoses, and environmental control systems.

PMID- 14645462
TI  - Evidence behind stroke rehabilitation.

PMID- 14645463
TI  - Rating scales for neurologists.

PMID- 14645464
TI  - Investigation and management of neurogenic bladder dysfunction.

PMID- 14645465
TI  - The management of motor neurone disease.

PMID- 14645466
TI  - Spike timing-dependent serotonergic neuromodulation of synaptic strength
      intrinsic to a central pattern generator circuit.
AB  - Neuromodulation is often thought to have a static, gain-setting function in
      neural circuits. Here we report a counter example: the neuromodulatory effect of
      a serotonergic neuron is dependent on the interval between its spikes and those
      of the neuron being modulated. The serotonergic dorsal swim interneurons (DSIs)
      are members of the escape swim central pattern generator (CPG) in the mollusk
      Tritonia diomedea. DSI spike trains heterosynaptically enhanced synaptic
      potentials evoked by another CPG neuron, ventral swim interneuron B (VSI-B), when
      VSI-B action potentials occurred within 10 sec of a DSI spike train; however, if
      VSI-B was stimulated 20-120 sec after DSI, then the amplitude of VSI-B synaptic
      potentials decreased. Consistent with this, VSI-B-evoked synaptic currents
      exhibited a temporally biphasic and bidirectional change in amplitude after DSI
      stimulation. Both the DSI-evoked enhancement and decrement were occluded by
      serotonin and blocked by the serotonin receptor antagonist methysergide,
      suggesting that both phases are mediated by serotonin. In most preparations,
      however, bath-applied serotonin caused only a sustained enhancement of VSI-B
      synaptic strength. The heterosynaptic modulation interacted with short-term
      homosynaptic plasticity: DSI-evoked depression was offset by VSI-B homosynaptic
      facilitation. This caused a complicated temporal pattern of neuromodulation when
      DSI and VSI-B were stimulated to fire in alternating bursts to mimic the natural
      motor pattern: DSI strongly enhanced summated VSI-B synaptic potentials and
      suppressed single synaptic potentials after the cessation of the artificial motor
      pattern. Thus, spike timing-dependent serotonergic neuromodulatory actions can
      impart temporal information that may be relevant to the operation of the CPG.

PMID- 14645467
TI  - Mechanism of toxicity in rotenone models of Parkinson's disease.
AB  - Exposure of rats to the pesticide and complex I inhibitor rotenone reproduces
      features of Parkinson's disease, including selective nigrostriatal dopaminergic
      degeneration and alpha-synuclein-positive cytoplasmic inclusions (Betarbet et
      al., 2000; Sherer et al., 2003). Here, we examined mechanisms of rotenone
      toxicity using three model systems. In SK-N-MC human neuroblastoma cells,
      rotenone (10 nm to 1 microm) caused dose-dependent ATP depletion, oxidative
      damage, and death. To determine the molecular site of action of rotenone, cells
      were transfected with the rotenone-insensitive single-subunit NADH dehydrogenase
      of Saccharomyces cerevisiae (NDI1), which incorporates into the mammalian ETC and
      acts as a "replacement" for endogenous complex I. In response to rotenone, NDI1
      transfected cells did not show mitochondrial impairment, oxidative damage, or
      death, demonstrating that these effects of rotenone were caused by specific
      interactions at complex I. Although rotenone caused modest ATP depletion,
      equivalent ATP loss induced by 2-deoxyglucose was without toxicity, arguing that
      bioenergetic defects were not responsible for cell death. In contrast, reducing
      oxidative damage with antioxidants, or by NDI1 transfection, blocked cell death.
      To determine the relevance of rotenone-induced oxidative damage to dopaminergic
      neuronal death, we used a chronic midbrain slice culture model. In this system,
      rotenone caused oxidative damage and dopaminergic neuronal loss, effects blocked
      by alpha-tocopherol. Finally, brains from rotenone-treated animals demonstrated
      oxidative damage, most notably in midbrain and olfactory bulb, dopaminergic
      regions affected by Parkinson's disease. These results, using three models of
      increasing complexity, demonstrate the involvement of oxidative damage in
      rotenone toxicity and support the evaluation of antioxidant therapies for
      Parkinson's disease.

PMID- 14645468
TI  - Progressive degradation and subsequent refinement of acoustic representations in
      the adult auditory cortex.
AB  - Correlated neuronal activity is believed to play an important role in refining
      and maintaining cortical circuitry during early development. Here we provide
      evidence that globally and locally correlated activity mediate different forms of
      adult plasticity. Pulses of broad-spectrum noise were used to activate time
      locked responses across large areas of the rat auditory cortex, globally
      synchronizing cortical activity. Brief tone pips were used to activate relatively
      small groups of neurons, generating locally correlated activity. Pairing pulsed
      noises with nucleus basalis (NB) stimulation in awake rats for 4 weeks broadened
      spectral tuning, disrupted tonotopic maps, and reduced spontaneous discharge
      correlation in the primary auditory cortex (AI), as examined under anesthesia.
      Those effects caused AI neurons to appear qualitatively similar to neurons in
      nonprimary auditory fields of naive animals. Subsequent pairing of tone pips with
      NB stimulation for a period of 4 weeks completely reversed these effects induced
      by previous noise-NB pairing. These findings further demonstrate that the adult
      auditory cortex retains a substantial capacity for receptive field plasticity and
      tonotopic map reorganization and that locally correlated activity plays an
      important role in plasticity in the adult, as in the developing cortex.

PMID- 14645469
TI  - Impact of photon noise on the reliability of a motion-sensitive neuron in the
      fly's visual system.
AB  - Variable behavioral responses to identical visual stimuli can, in part, be traced
      back to variable neuronal signals that provide unreliable information about the
      outside world. This unreliability in encoding of visual information is caused by
      several noise sources such as photon noise, synaptic noise, or the stochastic
      nature of ion channels. Neurons of the fly's visual motion pathway have been
      claimed to represent perfect encoders, with photon noise as the main noise source
      limiting their performance. Other studies on the fly's visual system suggest,
      however, that internal noise emerging within the nervous system also affects the
      reliability of motion vision. To resolve these contradictory interpretations, we
      performed an electrophysiological investigation, inspired by the "equivalent
      noise" paradigm applied in psychophysics, on the fly's motion-sensitive H1
      neuron. Noise-like brightness fluctuations of different strength were
      superimposed on the motion stimuli. Because the noise level found to affect the
      temporal properties of the spike responses is much larger than the estimate of
      photon noise under the experimental conditions, our results indicate that motion
      vision is more likely to be limited by internal sources of variability than by
      photon noise.

PMID- 14645470
TI  - Opioid modulation of scratching and spinal c-fos expression evoked by intradermal
      serotonin.
AB  - We investigated a spinal site for opioid modulation of itch-related scratching
      behavior in rats. Intradermal 5-HT (2%, 10 microl) elicited intermittent bouts of
      hindlimb scratching directed toward the injection site (nape of neck) beginning
      within minutes and lasting >1 hr. 5-HT-evoked scratching was significantly
      reduced by systemic administration of the opiate antagonist naltrexone but was
      not affected by systemic morphine at a dosage (3 mg/kg) that induces analgesia.
      Intradermal 5-HT elicited a significant increase in c-fos-like immunoreactivity
      (FLI) in superficial laminas I-III at the lateral aspect of the cervical C3-C6
      dorsal horn compared with controls receiving intradermal saline. Neither systemic
      morphine nor naltrexone significantly affected counts of 5-HT-evoked FLI. The
      lack of effect of morphine suggests that intradermal 5-HT activates dorsal horn
      neurons, signaling itch but not pain. Attenuation of 5-HT-evoked scratching but
      not spinal FLI by naltrexone suggests a supraspinal site for its antipruritic
      action. In contrast, morphine significantly attenuated FLI elicited by
      intradermal capsaicin, a chemical that induces pain but not scratching.

PMID- 14645471
TI  - Intracellular domains of NMDA receptor subtypes are determinants for long-term
      potentiation induction.
AB  - NMDA receptors (NMDARs) are essential for modulating synaptic strength at central
      synapses. At hippocampal CA3-to-CA1 synapses of adult mice, different NMDAR
      subtypes with distinct functionality assemble from NR1 with NR2A and/or NR2B
      subunits. Here we investigated the role of these NMDA receptor subtypes in long
      term potentiation (LTP) induction. Because of the higher NR2B contribution in the
      young hippocampus, LTP of extracellular field potentials could be enhanced by
      repeated tetanic stimulation in young but not in adult mice. Similarly, NR2B
      specific antagonists reduced LTP in young but only marginally in adult wild-type
      mice, further demonstrating that in mature CA3-to-CA1 connections LTP induction
      results primarily from NR2A-type signaling. This finding is also supported by
      gene-targeted mutant mice expressing C-terminally truncated NR2A subunits, which
      participate in synaptic NMDAR channel formation and Ca2+ signaling, as indicated
      by immunopurified synaptic receptors, postembedding immunogold labeling, and
      spinous Ca2+ transients in the presence of NR2B blockers. These blockers
      abolished LTP in the mutant at all ages, revealing that, without the
      intracellular C-terminal domain, NR2A-type receptors are deficient in LTP
      signaling. Without NR2B blockade, CA3-to-CA1 LTP was more strongly reduced in
      adult than young mutant mice but could be restored to wild-type levels by
      repeated tetanic stimulation. Thus, besides NMDA receptor-mediated Ca2+ influx,
      subtype-specific signaling is critical for LTP induction, with the intracellular
      C-terminal domain of the NR2 subunits directing signaling pathways with an age
      dependent preference.

PMID- 14645472
TI  - Brain-derived neurotrophic factor-induced gene expression reveals novel actions
      of VGF in hippocampal synaptic plasticity.
AB  - Synaptic strengthening induced by brain-derived neurotrophic factor (BDNF) is
      associated with learning and is coupled to transcriptional activation. However,
      identification of the spectrum of genes associated with BDNF-induced synaptic
      plasticity and the correlation of expression with learning paradigms in vivo has
      not yet been studied. Transcriptional analysis of BDNF-induced synaptic
      strengthening in cultured hippocampal neurons revealed increased expression of
      the immediate early genes (IEGs), c-fos, early growth response gene 1 (EGR1),
      activity-regulated cytoskeletal-associated protein (Arc) at 20 min, and the
      secreted peptide VGF (non-acronymic) protein precursor at 3 hr. The induced genes
      served as prototypes to decipher mechanisms of both BDNF-induced transcription
      and plasticity. BDNF-mediated gene expression was tyrosine kinase B and mitogen
      activated protein kinase-dependent, as demonstrated by pharmacological studies.
      Single-cell transcriptional analysis of Arc after whole-cell patch-clamp
      recordings indicated that increased gene expression correlated with enhancement
      of synaptic transmission by BDNF. Increased expression in vitro predicted
      elevations in vivo: VGF and the IEGs increased after trace eyeblink conditioning,
      a hippocampal-dependent learning paradigm. VGF protein was also upregulated by
      BDNF treatment and was expressed in a punctate manner in dissociated hippocampal
      neurons. Collectively, these findings suggested that the VGF neuropeptides may
      regulate synaptic function. We found a novel function for VGF by applying VGF
      peptides to neurons. C-terminal VGF peptides acutely increased synaptic charge in
      a dose-dependent manner, whereas N-terminal peptide had no effect. These
      observations indicate that gene profiling in vitro can reveal new mechanisms of
      synaptic strengthening associated with learning and memory.

PMID- 14645473
TI  - Theta and gamma oscillations during encoding predict subsequent recall.
AB  - Electrophysiological and hemodynamic measures of human brain activity have been
      shown to distinguish between episodes of encoding items that are later recalled
      versus those that are not recalled (Paller and Wagner, 2002). Using intracranial
      recordings from 793 widespread cortical and subcortical sites in 10 epileptic
      patients undergoing invasive monitoring, we compared oscillatory power at
      frequencies ranging from 2 to 64 Hz as participants studied lists of common
      nouns. Significant increases in oscillatory power during encoding predicted
      subsequent recall, with this effect predominantly in the 4-8 Hz (theta) and 28-64
      Hz (gamma) frequency bands. Sites exhibiting increased theta activity during
      successful encoding were clustered in right temporal and frontal cortex, whereas
      those exhibiting increased gamma activity appeared bilaterally at widespread
      cortical locations. These findings implicate theta and gamma oscillatory
      activity, across a widespread network of cortical regions, in the formation of
      new episodic memories.

PMID- 14645474
TI  - Developmental assembly of transduction apparatus in chick basilar papilla.
AB  - Hair cells, the sensory receptors of auditory and vestibular systems, use a
      transducer apparatus that renders them remarkably sensitive to mechanical
      displacement as minute as 1 nm. To study the embryonic development of the
      transducer apparatus in hair cells of the chick auditory papilla, we examined
      hair cells that have been labeled with N-(3-triethylammoniumpropyl)-4-(4
      (dibutylamino)styryl) pyridiniumdibromide, which has been shown to permeate the
      transducer channels. In addition, mechanotransduction currents were recorded
      directly using whole-cell patch-clamp techniques. The structure of the hair
      bundle was examined using scanning electron microscopy, and immunofluorescence
      labeling for myosin 1c, myosin 7a, and plasma membrane Ca2+ ATPase 2 was studied
      to determine the developmental expression of these proteins in embryonic chick
      papillas. We demonstrate that the transducer apparatus is assembled jointly at
      embryonic day 11 (E11) of the developing chick basilar papilla. The resting open
      probability of the transducer channels was high at E12 (approximately 0.5) and
      remained substantially elevated at E14-16; it then declined to the mature value
      of approximately 0.15 at E21. The displacement sensitivity of the transduction
      apparatus, the gating force, increased from E12 to E21. Although the expression
      of different components of the transducer apparatus and the transduction current
      peaked at approximately E14-16, marked refinement occurred beyond E16. For
      example, myosin 1c appeared diffusely localized in hair bundles from E12 to E16,
      but subsequently consolidated into punctate pattern. The fine temporal and
      precise spatial assembly of the transducer apparatus likely contributes toward
      the exquisite sensitivity of the transduction ensemble.

PMID- 14645475
TI  - Reward without dopamine.
AB  - Dopamine (DA) is believed to play a fundamental role in reward processes.
      Virtually all drugs of abuse activate dopaminergic systems, as do "natural"
      rewards such as sexual interaction and food. Sweet-tasting solutions, for
      example, are a well characterized natural reward. In the present experiments, we
      used mice that cannot make DA (DD mice) to test the hypothesis that DA is
      necessary for reward. Sucrose preference, assessed with a computerized
      "lickometer," was used to determine whether DD mice respond preferentially for
      rewarding stimuli. DD mice preferentially chose sucrose over water, and also
      preferred the noncaloric sweetener saccharin. Furthermore, the rate of licking,
      bout size, and length were greater in DD mice drinking sweets than in controls.
      These data refute the necessity of DA for the reward processes manifested by
      sucrose preference. However, DD mice initiated licking less frequently than
      control mice and had fewer total licks. We suggest that DD mice have a deficit of
      goal-directed behavior that is not specific to reward processes. Lastly, juvenile
      DD mice demonstrate robust sucrose preference before experience with food in the
      presence of DA. Thus, DA is not required for mice to learn to consume sweet
      solutions preferentially. We conclude that DA is not required to find the sweet
      tastes of sucrose or saccharin rewarding.

PMID- 14645476
TI  - CaV1.3 channels are essential for development and presynaptic activity of
      cochlear inner hair cells.
AB  - Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory
      nerve fibers in response to sound stimulation. During early development, afferent
      synaptic transmission is triggered by spontaneous Ca2+ spikes of IHCs, which are
      under efferent cholinergic control. Around the onset of hearing, large
      conductance Ca2+-activated K+ channels are acquired, and Ca2+ spikes as well as
      the cholinergic innervation are lost. Here, we performed patch-clamp measurements
      in IHCs of mice lacking the CaV1.3 channel (CaV1.3-/-) to investigate the role of
      this prevailing voltage-gated Ca2+ channel in IHC development and synaptic
      function. The small Ca2+ current remaining in IHCs from 3-week-old CaV1.3-/- mice
      was mainly mediated by L-type Ca2+ channels, because it was sensitive to
      dihydropyridines but resistant to inhibitors of non-L-type Ca2+ channels such as
      omega-conotoxins GVIA and MVIIC and SNX-482. Depolarization induced only marginal
      exocytosis in CaV1.3-/- IHC, which was solely mediated by L-type Ca2+ channels,
      whereas robust exocytic responses were elicited by photolysis of caged Ca2+.
      Secretion triggered by short depolarizations was reduced proportionally to the
      Ca2+ current, suggesting that the coupling of the remaining channels to
      exocytosis was unchanged. CaV1.3-/- IHCs lacked the Ca2+ action potentials and
      displayed a complex developmental failure. Most strikingly, we observed a
      continued presence of efferent cholinergic synaptic transmission and a lack of
      functional large-conductance Ca2+-activated K+ channels up to 4 weeks after
      birth. We conclude that CaV1.3 channels are essential for normal hair cell
      development and synaptic transmission.

PMID- 14645477
TI  - Gene profile of electroconvulsive seizures: induction of neurotrophic and
      angiogenic factors.
AB  - Electroconvulsive seizure therapy (ECS) is a clinically proven treatment for
      depression and is often effective even in patients resistant to chemical
      antidepressants. However, the molecular mechanisms underlying the therapeutic
      efficacy of ECS are not fully understood. One theory that has gained attention is
      that ECS and other antidepressants increase the expression of select neurotrophic
      factors that could reverse or block the atrophy and cell loss resulting from
      stress and depression. To further address this topic, we examined the expression
      of other neurotrophic-growth factors and related signaling pathways in the
      hippocampus in response to ECS using a custom growth factor microarray chip. We
      report the regulation of several genes that are involved in growth factor and
      angiogenic-endothelial signaling, including neuritin, stem cell factor, vascular
      endothelial growth factor (VEGF), VGF (nonacronymic), cyclooxygenase-2, and
      tissue inhibitor of matrix metalloproteinase-1. Some of these, as well as other
      growth factors identified, including VEGF, basic fibroblast growth factor, and
      brain-derived neurotrophic factor, have roles in mediating neurogenesis and cell
      proliferation in the adult brain. We also examined gene expression in the choroid
      plexus and found several growth factors that are enriched in this vascular tissue
      as well as regulated by ECS. These data suggest that an amplification of growth
      factor signaling combined with angiogenic mechanisms could have an important role
      in the molecular action of ECS. This study demonstrates the applicability of
      custom-focused microarray technology in addressing hypothesis-driven questions
      regarding the action of antidepressants.

PMID- 14645478
TI  - Correlated discharge among cell pairs within the oculomotor horizontal velocity
      to-position integrator.
AB  - In the oculomotor system, temporal integration of velocity commands into position
      signals may depend on synaptic feedback among neurons of a bilateral brainstem
      cell assembly known as the "neural integrator." Both ipsilateral excitatory and
      contralateral inhibitory projections between eye position-related integrator
      cells are hypothesized as a substrate for positive feedback supporting
      integration. Presence of feedback interactions should be evident in cross
      correlation functions of neuron pairs. Here, unilateral and bilateral paired
      recordings were obtained during fixation behavior from neurons in goldfish
      brainstem area I, a key element of the integrator. During fixations, discharge of
      most unilateral pairs, composed of cells with eye position sensitivities of the
      same sign, was positively correlated with lag of 0-10 msec (n = 11 of 14
      significant). Typically, a very narrow peak (mean half-width <4 msec) near zero
      lag was observed. Discharge of bilateral pairs, composed of cells with position
      sensitivities of the opposite sign, was either negatively correlated with lag of
      0-10 msec (n = 5 of 13 significant) or not correlated. Troughs in negative
      correlations always had minima between 3 and 5 msec lag. These results are
      consistent with the feedback hypothesis of temporal integration, highlighting
      excitation unilaterally and inhibition bilaterally. Absence of visual input did
      not weaken correlations, but other sources of correlated input extrinsic to area
      I were not ruled out. Triplet recordings revealed that unilateral pairwise
      correlations were primarily independent. Correlation between unilateral pairs
      systematically decreased with increasing eye position, demonstrating that
      synchrony is not necessary for persistent activity at high firing rates.

PMID- 14645479
TI  - Long-term K+ channel-mediated dampening of dopamine neuron excitability by the
      antipsychotic drug haloperidol.
AB  - Antipsychotic drugs require days of treatment to begin to produce therapeutic
      effects. We report that in vivo treatment with the antipsychotic drug haloperidol
      acts with a delay of days to slow spontaneous repetitive firing by isolated
      midbrain dopamine neurons. The decreased excitability is caused by an increased
      number of functional A-type K+ channels without any change in gating properties.
      Upregulation of dopamine neuron Kv4.3 mRNA accounts for this effect,
      demonstrating a role for channel gene expression in this delayed drug action. The
      resultant long-term dampening of dopamine neuron excitability may serve to tone
      down the dopamine system.

PMID- 14645480
TI  - Priming stimulation enhances the depressant effect of low-frequency repetitive
      transcranial magnetic stimulation.
AB  - Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can
      depress the excitability of the cortex locally and has been proposed for the
      treatment of disorders such as schizophrenia and epilepsy. Some have speculated
      that the depressant effect is related to long-term depression (LTD) of cortical
      synapses. Because in vitro LTD can be enhanced by pretreatment of synapses with
      higher-frequency stimulation, we hypothesized that if rTMS depression had
      mechanisms in common with LTD, higher-frequency priming would increase it also.
      In 25 healthy volunteers in two experiments, we measured motor-evoked potentials
      (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold
      rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor
      cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the
      MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found
      significant increases in the amount of cortical depression with both types of 6
      Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS
      showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz
      rTMS depression and LTD. Although not conclusive evidence, this strengthens the
      case for overlapping mechanisms and suggests a potent new technique for enhancing
      low-frequency rTMS depression that may have experimental and clinical
      applications.

PMID- 14645481
TI  - Molecular basis for ultraviolet vision in invertebrates.
AB  - Invertebrates are sensitive to a broad spectrum of light that ranges from UV to
      red. Color sensitivity in the UV plays an important role in foraging, navigation,
      and mate selection in both flying and terrestrial invertebrate animals. Here, we
      show that a single amino acid polymorphism is responsible for invertebrate UV
      vision. This residue (UV: lysine vs blue:asparagine or glutamate) corresponds to
      amino acid position glycine 90 (G90) in bovine rhodopsin, a site affected in
      autosomal dominant human congenital night blindness. Introduction of the
      positively charged lysine in invertebrates is likely to deprotonate the Schiff
      base chromophore and produce an UV visual pigment. This same position is
      responsible for regulating UV versus blue sensitivity in several bird species,
      suggesting that UV vision has arisen independently in invertebrate and vertebrate
      lineages by a similar molecular mechanism.

PMID- 14645482
TI  - Amyloid-beta antibody treatment leads to rapid normalization of plaque-induced
      neuritic alterations.
AB  - The accumulation of amyloid-beta into insoluble plaques is a characteristic
      feature of Alzheimer's disease. Neuronal morphology is distorted by plaques:
      rather than being essentially straight, they are substantially more curved than
      those in control tissue, their trajectories become altered, and they are
      frequently distended or swollen, presumably affecting synaptic transmission.
      Clearance of plaques by administration of antibodies to amyloid-beta is a
      promising therapeutic approach to the treatment of Alzheimer's disease, leading
      to stabilization of dementia by an unknown cellular mechanism. The effect of
      plaque clearance on plaque-induced neuronal alterations has not been studied
      previously. Here we show that both plaques and neuritic lesions are reversible in
      a strikingly short period of time after administration of a single dose of
      amyloid-beta antibody. Amyloid clearance and recovery of normal neuronal
      geometries were observed as early as 4 d and lasted at least 32 d after a single
      treatment. These results demonstrate that, once plaques are cleared, neuronal
      morphology is self-correcting and that passive antibody treatment has the
      potential to reverse neuronal damage caused by Alzheimer's disease and, hence,
      directly impact cognitive decline. Moreover, the rapid normalization of neuritic
      dystrophy suggests an unexpected degree of plasticity in the adult nervous
      system.

PMID- 14645483
TI  - The sleep-modulating peptide cortistatin augments the h-current in hippocampal
      neurons.
AB  - Cortistatin (CST) is a sleep-modulating peptide found exclusively in the brain.
      Although CST is closely related to somatostatin (SST) and binds to SST receptors,
      CST has effects on sleep and neuronal activity in cortex and hippocampus that
      differ from SST. To uncover the cellular mechanisms affected by CST, we studied
      the electrophysiological postsynaptic effects of CST and assessed its interaction
      with SST on hippocampal CA1 pyramidal neurons. CST altered intrinsic membrane
      properties and occluded SST effects, indicating that both peptides similarly
      augment the sustained K+ M- and leak-currents (IM and IK(L)). In the presence of
      SST, however, CST elicited an additional inwardly rectifying component in the
      hyperpolarized range. This effect was unaffected by barium, used to block K+
      currents, but was completely prevented by the selective h-current (Ih) blocker
      ZD7288. CST, but not SST, selectively increased Ih in a concentration-dependent
      manner by augmenting its maximum conductance. CST did not shift the Ih activation
      curve, and the peptide effect was unaffected by a membrane-permeable analog of
      cAMP. We conclude that CST and SST similarly increase K+ conductances in
      hippocampal neurons, most likely by activating SST receptors. However, CST
      additionally augments Ih, a voltage-dependent current that plays a key role in
      the modulation of synaptic integration and regulates oscillatory activity. Our
      results indicate that CST targets a specific conductance unaffected by SST to
      modulate cellular mechanisms implicated in sleep regulation.

PMID- 14645484
TI  - Caught in the act: in vivo mapping of macrophage infiltration in nerve injury by
      magnetic resonance imaging.
AB  - In vivo tracking of hematogenous macrophages has been a major challenge because
      these cells are key players in nerve injury and repair. We visualized the
      spatiotemporal course of macrophage infiltration after acute peripheral nerve
      injury in living rats by using superparamagnetic iron oxide (SPIO) particles and
      magnetic resonance imaging (MRI). A signal loss on MR images indicating iron
      accumulation was present in degenerating sciatic nerves between days 1 and 8
      after a crush lesion, ceased thereafter, and corresponded to the transient
      presence of iron-labeled ED1-positive macrophages in tissue sections. In
      contrast, no SPIO accumulation was seen after optic nerve crush, which revealed
      microglial activation but lacked macrophage infiltration. SPIO-enhanced MRI
      provides a new tool to selectively visualize active periods of macrophage
      transmigration into the nervous system, thus enabling dynamic views on a
      fundamental process in a multitude of nerve disorders.

PMID- 14645485
TI  - Sleep-dependent theta oscillations in the human hippocampus and neocortex.
AB  - Hippocampal theta waves recorded during rapid eye movement (REM) sleep are
      thought to play a critical role in memory consolidation in lower mammals, but
      previous attempts to detect similar theta oscillations in the human hippocampus
      have been unsuccessful. Using subdural and depth recordings from epileptic
      patients, we now report the first evidence of state-dependent hippocampal theta
      waves (4-7 Hz) in humans. Unlike the continuous theta in rodents, however, these
      oscillations were consistently observed during REM sleep in short (approximately
      1 sec) bursts and during transitions to wake in longer epochs. Theta waves were
      also observed in the basal temporal lobe and frontal cortex during transitions
      from sleep to wake and in quiet wakefulness but not in REM, and they were not
      coherent with hippocampal theta oscillations. The absence of functional coupling
      between neocortex and hippocampus during theta periods indicates that multiple
      theta generators exist in the human brain, and that they are dynamically
      regulated by brain state. Gamma oscillations were also present during REM theta
      bursts, but the fluctuations in gamma power were not associated with theta phase,
      pointing out another significant difference between rodent and human theta
      properties. Together, these findings suggest that the generation mechanisms of
      theta oscillations in humans might have evolved from tonic to phasic in
      hippocampus during REM sleep and extended from hippocampus to cortex, where they
      appear in certain wakefulness-related states.

PMID- 14645486
TI  - Distinct GABAergic targets of feedforward and feedback connections between lower
      and higher areas of rat visual cortex.
AB  - Processing of visual information is performed in different cortical areas that
      are interconnected by feedforward (FF) and feedback (FB) pathways. Although FF
      and FB inputs are excitatory, their influences on pyramidal neurons also depend
      on the outputs of GABAergic neurons, which receive FF and FB inputs. Rat visual
      cortex contains at least three different families of GABAergic neurons that
      express parvalbumin (PV), calretinin (CR), and somatostatin (SOM) (Gonchar and
      Burkhalter, 1997). To examine whether pathway-specific inhibition (Shao and
      Burkhalter, 1996) is attributable to distinct connections with GABAergic neurons,
      we traced FF and FB inputs to PV, CR, and SOM neurons in layers 1-2/3 of area 17
      and the secondary lateromedial area in rat visual cortex. We found that in layer
      2/3 maximally 2% of FF and FB inputs go to CR and SOM neurons. This contrasts
      with 12-13% of FF and FB inputs onto layer 2/3 PV neurons. Unlike inputs to layer
      2/3, connections to layer 1, which contains CR but lacks SOM and PV somata, are
      pathway-specific: 21% of FB inputs go to CR neurons, whereas FF inputs to layer 1
      and its CR neurons are absent. These findings suggest that FF and FB influences
      on layer 2/3 pyramidal neurons mainly involve disynaptic connections via PV
      neurons that control the spike outputs to axons and proximal dendrites. Unlike FF
      input, FB input in addition makes a disynaptic link via CR neurons, which may
      influence the excitability of distal pyramidal cell dendrites in layer 1.

PMID- 14645487
TI  - Long-lasting functional disabilities in middle-aged rats with small cerebral
      infarcts.
AB  - Recommendations from experts and recently established guidelines on how to
      improve the face and predictive validity of animal models of stroke have stressed
      the importance of using older animals and long-term behavioral-functional
      endpoints rather than relying almost exclusively on acute measures of infarct
      volume in young animals. The objective of the present study was to determine
      whether we could produce occlusions in older rats with an acceptable mortality
      rate and then detect reliable, long-lasting functional deficits. A reversible
      intraluminar suture middle cerebral artery occlusion (MCAO) procedure was used to
      produce small infarcts in middle-aged rats. This resulted in an acceptable
      mortality rate, and robust disabilities were detected in functional assays,
      although the degree of total tissue loss measured 90 d after MCAO was quite
      modest. Infarcted animals were functionally impaired relative to sham control
      animals even 90 d after the occlusions, and when animals were subgrouped based on
      amount of tissue loss, MCAO animals with only 4% tissue loss exhibited enduring
      neurological-behavioral impairments relative to sham-operated controls, and the
      functional impairments in the group with the largest infarcts (20% tissue loss)
      were more severe than the functional impairments in the rats with 4% tissue loss.
      These results suggest that this model, using reversible MCAO to produce small
      infarcts and long-lasting functional-behavioral deficits in older rats, may
      represent an advance in the relatively higher-throughput modeling of stroke and
      its recovery in rodents and may be useful in the development and characterization
      of future stroke therapies.

PMID- 14645488
TI  - Sustained Ca2+ entry elicits transient postsynaptic currents at a retinal ribbon
      synapse.
AB  - Night (scotopic) vision is mediated by a distinct retinal circuit in which the
      light responses of rod-driven neurons are faster than those of the rods
      themselves. To investigate the dynamics of synaptic transmission at the second
      synapse in the rod pathway, we made paired voltage-clamp recordings from rod
      bipolar cells (RBCs) and postsynaptic AII and A17 amacrine cells in rat retinal
      slices. Depolarization of RBCs from -60 mV elicited sustained Ca2+ currents and
      evoked AMPA receptor (AMPAR)-mediated EPSCs in synaptically coupled amacrine
      cells that exhibited large, rapidly rising initial peaks that decayed rapidly to
      smaller, steady-state levels. The transient component persisted in the absence of
      feedback inhibition to the RBC terminal and when postsynaptic AMPA receptor
      desensitization was blocked with cyclothiazide, indicating that it reflects a
      time-dependent decrease in the rate of exocytosis from the presynaptic terminal.
      The EPSC waveform was similar when RBCs were recorded in perforated-patch or
      whole-cell configurations, but asynchronous release from RBCs was enhanced when
      the intraterminal Ca2+ buffer capacity was reduced. When RBCs were depolarized
      from -100 mV, inactivating, low voltage-activated (T-type channel-mediated) Ca2+
      currents were evident. Although Ca2+ influx through T-type channels boosted
      vesicle release, as reflected by larger EPSCs, it did not make the EPSCs faster,
      indicating that activation of T-type channels is not necessary to generate a
      transient phase of exocytosis. We conclude that the time course of vesicle
      release from RBCs is inherently transient and, together with the fast kinetics of
      postsynaptic AMPARs, speeds transmission at this synapse.

PMID- 14645489
TI  - Neurosteroids shift partial agonist activation of GABA(A) receptor channels from
      low- to high-efficacy gating patterns.
AB  - Although GABA activates synaptic (alphabetagamma) GABA(A) receptors with high
      efficacy, partial agonist activation of alphabetagamma isoforms and GABA
      activation of the primary extrasynaptic (alphabetadelta) GABA(A) receptors are
      limited to low-efficacy activity, characterized by minimal desensitization and
      brief openings. The unusual sensitivity of alphabetadelta receptor channels to
      neurosteroid modulation prompted investigation of whether this high sensitivity
      was dependent on the delta subunit or the low-efficacy channel function that it
      confers. We show that the isoform specificity (alphabetadelta > alphabetagamma)
      of neurosteroid modulation could be reversed by conditions that reversed isoform
      specific activity modes, including the use of beta-alanine to achieve increased
      efficacy with alphabetadelta receptors and taurine to render alphabetagamma
      receptors low efficacy. We suggest that neurosteroids preferentially enhance low
      efficacy GABA(A) receptor activity independent of subunit composition. Allosteric
      conversion of partial to full agonism may be a general mechanism for reversibly
      scaling the efficacy of GABA(A) receptors to endogenous partial agonists.

PMID- 14645490
TI  - Dual regulation of calcium oscillation in astrocytes by growth factors and pro
      inflammatory cytokines via the mitogen-activated protein kinase cascade.
AB  - In response to neurotransmitters, astrocytes show various types of calcium
      increase (transient, oscillatory, and complex), the physiological significance of
      which is still controversial. To explore this variability, we examined factors
      affecting the calcium increase pattern in cultured astrocytes and investigated
      the consequences of the astrocytic calcium response in slice preparations. We
      found that growth factors (GFs) (EGF plus basic FGF) promoted calcium oscillation
      in response to glutamate, ATP, or thimerosal (which directly activates the
      inositol-1,4,5 triphosphate receptor) and that this effect was suppressed by pro
      inflammatory cytokines (interleukin-1beta or tumor necrosis factor-alpha),
      lipopolysaccharide, or a MEK (mitogen-activated protein kinase kinase) inhibitor,
      suggesting dual regulation of calcium oscillation in astrocytes by factors
      affecting brain function and pathology via the mitogen-activated protein kinase
      (MAPK) cascade. The calcium oscillation was accompanied by enlargement of the
      calcium store, cell proliferation, and the development of a hypertrophic
      morphology. The cytokines suppressed GF-induced MAPK-dependent immediate early
      gene promoter activation, but not phosphorylation of extracellular signal
      regulated kinase (ERK), showing that they affected gene regulation by acting on
      the MAPK cascade downstream of ERK. In slice preparations, a metabotropic
      glutamate receptor agonist converted the spontaneous neuronal calcium increase,
      attributable to synaptic transmission, to an oscillatory response similar to that
      seen in astrocytes in culture, indicating that the calcium response in astrocytes
      acted as a feedback mechanism on the activity of neighboring neurons. This is the
      first evidence for a dual regulation of calcium oscillation by physiological
      factors and for the control of calcium dynamics actually being used in
      physiological processes.

PMID- 14645491
TI  - Multiple molecular determinants for allosteric modulation of alternatively
      spliced AMPA receptors.
AB  - Positive allosteric regulation of glutamate AMPA receptors involves
      conformational changes that can attenuate receptor desensitization and enhance
      ion flux through the channel pore. Many allosteric modulators (e.g.,
      cyclothiazide and aniracetam) preferentially affect the flip (i) or flop (o)
      alternatively spliced isoform of AMPA receptors, implicating residues in the flip
      flop domain as critical determinants of splice variant sensitivity. Indeed,
      previous mutational analyses have demonstrated that the differential sensitivity
      to cyclothiazide and aniracetam depends on a single amino acid, Ser (flip) and
      Asn (flop), suggesting that this residue may be solely responsible for
      differences in modulation of AMPA receptor isoforms. The present studies tested
      this hypothesis by investigating the molecular determinants of modulation of AMPA
      receptor splice variants by a structurally distinct compound, LY404187, which
      displays strikingly different and opposing kinetics of allosteric regulation
      characterized by a time-dependent enhancement in potentiation of homomeric GluR1
      GluR4i and a time-dependent reduction in potentiation of GluR1-GluR4o. Site
      directed mutagenesis of residues in the flip-flop domain of GluR2 revealed that,
      although exchange of Asn775 for Ser in GluR2o was sufficient to confer the GluR2i
      phenotype of potentiation, the corresponding mutation, Ser775Asn, in GluR2i did
      not impart the GluR2o response. In fact, the GluR2o kinetics of modulation
      depended on a novel set of substitutions in GluR2i, including Thr765Asn,
      Pro766Ala, and Val779Leu in combination with Ser775Asn. Collectively, these
      results show that, unlike cyclothiazide and aniracetam, the residues that confer
      splice variant differences in modulation by LY404187 are not identical and
      indicate that allosteric regulation of AMPA receptors can arise from multiple
      molecular determinants.

PMID- 14645492
TI  - Corpus callosum deficiency in transgenic mice expressing a truncated ephrin-A
      receptor.
AB  - The A-class of the erythropoietin-producing hepatocellular carcinoma cell-derived
      (EphA) tyrosine kinase receptors and their ligands, the A-ephrins, play critical
      roles in the specification of topographic axon projection maps during
      development. In this study, the role of the EphA subfamily in callosal
      projections was investigated using transgenic mice expressing a kinase deletion
      mutant of EphA5. In approximately half of these transgenic mice, cerebral
      cortical neurons in various cortical regions (primary and secondary somatosensory
      cortices and frontal as well as visual areas) failed to project to the
      contralateral cortex. When commissural axons were examined with DiI labeling, few
      callosal fibers were found to traverse the midline in both the adult and neonatal
      transgenic mice. This defect in callosal development correlates with the
      expression of the transgene, because neurons in the superficial layers of the
      motor cortex, where transgene expression is low, show normal contralateral
      projection through the corpus callosum. In addition, multiple EphA receptors are
      expressed in callosal neurons and ephrin-A5 stimulates neurite outgrowth of
      callosal neurons in vitro. The midline glia structures important for callosal
      axon midline crossing appear normal in the transgenic mice, suggesting that the
      defects are unrelated to defective guidance structures at the midline. These
      observations suggest critical functions for EphA receptor in establishing
      callosal connections during brain development.

PMID- 14645493
TI  - The development of a single frequency place in the mammalian cochlea: the
      cochlear resonance in the mustached bat Pteronotus parnellii.
AB  - Cochlear microphonic potentials (CMs) were recorded from the sharply tuned,
      strongly resonant auditory foveae of 1- to 5-week-old mustached bats that were
      anesthetized with Rompun and Ketavet. The fovea processes Doppler-shifted echo
      responses of the constant-frequency component of echolocation calls. During
      development, the frequency and tuning sharpness of the cochlear resonance
      increases, and CM ringing persists for longer after the tone. CM is relatively
      insensitive at tone onset and grows linearly with increased stimulus level.
      During the tone, the CM is more sensitive and grows compressively with increased
      stimulus level and phase leads onset CM by 90 degrees for frequencies below the
      resonance. CM during the ringing is also sensitive and compressive and phase
      leads onset CM by 180 degrees below the resonance and lags it by 180 degrees
      above the resonance. Throughout postnatal development, CMs measured during the
      tone and in the ringing increase both in sensitivity and compression. The
      cochlear resonance appears to be attributable to interaction between two
      oscillators. The more broadly tuned oscillator dominates the onset response, and
      the narrowly tuned oscillator dominates the ringing. Early in development,
      mechanical coupling between the oscillators results in a relatively broadly tuned
      system with several frequency modes in the CM at tone onset and in the CM
      ringing. Beating occurs between the resonance and the stimulus response during
      the tone and between two components of the narrowly tuned oscillator at tone
      offset. At maturity, the CM has three modes for frequencies within 10 kHz of the
      resonance at tone onset and a single, sharply tuned mode in the ringing.

PMID- 14645494
TI  - Adenosinergic protection of dopaminergic and GABAergic neurons against
      mitochondrial inhibition through receptors located in the substantia nigra and
      striatum, respectively.
AB  - Mitochondrial dysfunction may contribute to dopaminergic (DAergic) cell death in
      Parkinson's disease and GABAergic cell death in Huntington's disease. In the
      present work, we tested whether blocking A1 receptors could enhance the damage to
      DAergic and GABAergic neurons caused by mitochondrial inhibition, and whether
      blocking A2a receptors could protect against damage in this model. Animals
      received an intraperitoneal injection of 8-cyclopentyl-1,3-dipropylxanthine (CPX)
      (A1 antagonist) or 3,7-dimethyl-1-propargylxanthine (DMPX) (A2a antagonist) 30
      min before intrastriatal infusion of malonate (mitochondrial complex II
      inhibitor). Damage was assessed 1 week later by measuring striatal dopamine,
      tyrosine hydroxylase (TH), and GABA content. In mice and rats, malonate-induced
      depletion of striatal dopamine, TH, or GABA was potentiated by pretreatment with
      1 mg/kg CPX and attenuated by pretreatment with 5 mg/kg DMPX. To determine the
      location of the A1 and A2a receptors mediating these effects, CPX or DMPX was
      infused directly into the striatum or substantia nigra of rats 30 min before
      intrastriatal infusion of malonate. When infused into the striatum, CPX (20 ng)
      potentiated, whereas DMPX (50 ng) prevented malonate-induced GABA loss, but up to
      100 ng of CPX or 500 ng of DMPX did not alter malonate-induced striatal dopamine
      loss. Intranigral infusion of CPX (100 ng) or DMPX (500 ng), however, did
      exacerbate and protect, respectively, against malonate-induced striatal dopamine
      loss. Thus, A1 receptor blockade enhances and A2a receptor blockade protects
      against damage to DAergic and GABAergic neurons caused by mitochondrial
      inhibition. Interestingly, these effects are mediated by A1 and A2a receptors
      located in the substantia nigra for DAergic neurons and in the striatum for
      GABAergic neurons.

PMID- 14645495
TI  - Peptidergic nociceptors of both trigeminal and dorsal root ganglia express
      serotonin 1D receptors: implications for the selective antimigraine action of
      triptans.
AB  - Agonists at serotonin 1D (5-HT1D) receptors relieve migraine headache but are not
      clinically used as general analgesics. One possible explanation for this
      difference is that 5-HT1D receptors are preferentially expressed by cranial
      afferents of the trigeminal system. We compared the distribution of 5-HT1D
      receptor-immunoreactive (5-HT1D-IR) peripheral afferents within the trigeminal
      ganglion (TRG) and lumbar dorsal root ganglion (DRG) of the rat. We also examined
      the neurochemical identity of 5-HT1D-IR neurons with markers of primary afferent
      nociceptors, peripherin, isolectin B4, and substance P, and markers of myelinated
      afferents, N52 and SSEA3. We observed a striking similarity in the size,
      distribution, and neurochemical identity of 5-HT1D-IR neurons in TRG and lumbar
      DRG afferents. Furthermore, the vast majority of 5-HT1D-IR neurons are
      unmyelinated peptidergic afferents that distribute peripherally, including the
      dura, cornea, and the sciatic nerve. In the central projections of these
      afferents within the trigeminal nucleus caudalis and the spinal cord dorsal horn,
      5-HT1D-IR fibers are concentrated in laminas I and outer II; a few axons
      penetrate to lamina V. At the ultrastructural level, 5-HT1D receptors in the
      spinal cord dorsal horn are localized exclusively within dense core vesicles of
      synaptic terminals. We observed scattered 5-HT1D-IR neurons in the nodose
      ganglia, and there was sparse terminal immunoreactivity in the solitary nucleus.
      The visceral efferents of the superior cervical ganglia did not contain 5-HT1D
      immunoreactivity. Our finding, that 5-HT1D receptors are distributed in
      nociceptors throughout the body, raises the possibility that triptans can
      regulate not only headache-associated pain but also nociceptive responses in
      extracranial tissues.

PMID- 14645496
TI  - The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone
      production.
AB  - Aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex is
      regulated by transcription of CYP11B2 (encoding aldosterone synthase). The
      effects of nerve growth factor-induced clone B (NGFIB) (NR4A1), Nur-related
      factor 1 (NURR1) (NR4A2), and steroidogenic factor-1 (SF-1) (NR5A1) on
      transcription of human CYP11B2 (hCYP11B2) and hCYP11B1 (11 beta-hydroxylase) were
      compared in human H295R adrenocortical cells. hCYP11B2 expression was increased
      by NGFIB and NURR1. Although hCYP11B1 was activated by SF-1, cotransfection with
      SF-1 inhibited activation of hCYP11B2 by NGFIB and NURR1. NGFIB and NURR1
      transcript and protein levels were strongly induced by angiotensin (Ang) II, the
      major regulator of hCYP11B2 expression in vivo. Sequential deletion and
      mutagenesis of the hCYP11B2 promoter identified two functional NGFIB response
      elements (NBREs), one located at -766/-759 (NBRE-1) and the previously studied
      Ad5 element at -129/-114. EMSAs suggested that both elements bound NGFIB and
      NURR1. In human adrenals, NURR1 immunoreactivity was preferentially localized in
      the zona glomerulosa and to a lesser degree in the zona fasciculata, whereas
      NGFIB was detected in both zones. The calmodulin kinase inhibitor KN93 partially
      blocked K(+)-stimulated transcription of NGFIB and NURR1. KN93 partially
      inhibited the effect of Ang II on NURR1 mRNA levels but did not modify the effect
      on expression of NGFIB. Mutation of the NBRE-1, Ad5, and Ad1/cAMP response
      element (CRE) cis-elements reduced both basal and Ang II-induced levels of
      hCYP11B2, demonstrating that all three elements are important for maximal
      transcriptional activity. Our results suggest that NGFIB and NURR1 are key
      regulators of hCYP11B2 expression and may partially mediate the regulation of
      hCYP11B2 by Ang II.

PMID- 14645497
TI  - Deoxyribonucleic acid response element-dependent regulation of transcription by
      orphan nuclear receptor estrogen receptor-related receptor gamma.
AB  - The estrogen receptor-related receptor gamma (ERR gamma/ERR3/NR3B3) is the newest
      member of the ERR subfamily that also includes ERR alpha and ERR beta. All three
      isoforms share a high degree of amino acid identity especially in the DNA binding
      domain. ERR gamma is a constitutively active transcriptional activator that
      regulates reporter elements driven by steroidogenic factor 1 response element (SF
      1RE) and estrogen response element. However, it has the highest potency on a
      derivative of SF-1RE present in the small heterodimer partner gene promoter
      called sft4 and unlike ERR alpha and -beta, it fails to activate a palindromic
      thyroid hormone response element. To investigate the mechanism behind this
      response element-specific differential transcriptional activity of ERR gamma, the
      interactions of ERR gamma and the aforementioned response elements was monitored.
      EMSA and chromatin immunoprecipitation assays demonstrated that ERR gamma binds
      to sft4, SF-1RE, and palindromic thyroid hormone response element albeit with
      different degrees of affinity, but causes hyperacetylation of sft4 and SF-1RE
      templates only. Limited proteolysis assays showed that ERR gamma, bound to
      different elements, shows differential trypsin sensitivity. A search for novel
      coregulators of ERR gamma led to the identification of receptor interacting
      protein 140 as a potent corepressor and peroxisome proliferator-activated
      receptor gamma coactivator 1 as a potent coactivator of ERR gamma. DNA-dependent
      pull-down and transient transfection assays demonstrated that, on different DNA
      elements, ERR gamma exhibits differential cofactor interactions, which in turn
      dictate its transcriptional activity. Because ERR gamma shows a similar tissue
      distribution as peroxisome proliferator-activated receptor gamma coactivator 1
      and receptor interacting protein 140, these two coregulators may act as key
      components of ERR gamma-mediated transcription.

PMID- 14645498
TI  - Potent ligand-independent estrogen receptor activation by 3,3'-diindolylmethane
      is mediated by cross talk between the protein kinase A and mitogen-activated
      protein kinase signaling pathways.
AB  - We investigated the mechanism of ligand-independent activation of the estrogen
      receptor (ER) by 3,3'-diindolylmethane (DIM), a promising anticancer agent
      derived from vegetables of the Brassica genus, in Ishikawa and HEC-1B human
      endometrial cancer cells. DIM stimulated the activity of an ER-responsive
      reporter by over 40-fold, equivalent to the maximum induction produced by
      estradiol (E2), whereas cotreatment of cells with the ER antagonist, ICI-182,780
      (ICI), abolished the stimulatory effect of DIM. DIM also induced the expressions
      of the endogenous genes, TGF-alpha, alkaline phosphatase, and progesterone
      receptor similar to levels induced by E2. Induction of gene expression by DIM was
      inhibited by the protein synthesis inhibitor, cycloheximide. In addition,
      cotreatment of cells with the protein kinase A (PKA) inhibitor, H89, or the MAPK
      inhibitor, PD98059, reduced DIM activation of the ER by 75% and 50%,
      respectively. Simultaneous treatment of cells with both inhibitors completely
      abolished the effect of DIM. DIM stimulated MAPK activity and induced
      phosphorylation of the endogenous PKA target, cAMP response element binding
      protein (CREB), in a PKA-dependent manner. Expression of MCREB, a
      nonphosphorylatable CREB mutant, partially abolished activation of the ER by DIM.
      These results demonstrate that DIM is a mechanistically novel activator of the ER
      that requires PKA-dependent phosphorylation of CREB.

PMID- 14645499
TI  - CpG methylation and transcription factors Sp1 and Sp3 regulate the expression of
      the human secretin receptor gene.
AB  - The human secretin receptor (hSR) is an important glycoprotein receptor for
      regulating the secretion of pancreatic bicarbonate, water, and electrolytes. In
      this study we investigated the transcriptional regulation of the hSR gene. A
      minimal 106-bp promoter was identified, and it contains two GC boxes (GC box-A, 
      240 to -226; and GC box-B, -203 to -194, from the translation start site). EMSA
      and supershift analyses showed that both GC boxes interact with Sp1 and Sp3
      transcription factors. Transient transfection in pancreas-derived human
      pancreatic ductule carcinoma (PANC)-1 and bovine pancreatic duct-1 cells showed
      that mutation of either GC box-A or -B reduced the promoter strength by 56-67%,
      whereas mutation of both GC boxes caused more than 90% reduction of promoter
      activity. Cotransfections of the hSR promoter with Sp1 and Sp3 expression vectors
      in Sp-deficient Drosophila SL-2 Schneider cells further demonstrated that the
      ratio of Sp1 to Sp3 is the key mechanism to modulate hSR gene expression. The
      methylation statuses of 27 CpG sites within the promoter region (-400 to -151 bp)
      were assessed in various human pancreas and liver cell lines. The hSR promoter is
      unmethylated (CAPAN-1, human pancreatic adenocarcinoma) or partially methylated
      (PANC-1 and HPAC, human pancreatic adenocarcinoma) in hSR-expressing cell lines
      but is completely methylated in hSR nonexpressing HepG2 cells. Methyltransferase
      inhibitor 5-aza-2'deoxycytidine increased hSR gene expression level in PANC-1
      cells and induced hSR gene expression in HepG2 cells. Together, our study shows
      that, in addition to Sp1 and Sp3, promoter methylation also plays a role in the
      regulation of hSR gene expression.

PMID- 14645500
TI  - Puralpha, a single-stranded deoxyribonucleic acid binding protein, augments
      placental lactogen gene transcription.
AB  - Placental lactogen (PL) is thought to alter maternal metabolism to increase the
      pool of nutrients available for the fetus and to stimulate fetal nutrient uptake.
      The ovine (o) PL gene is expressed in chorionic binucleate cells (oBNC) and cis
      elements located within the proximal promoter (-124 to +16 bp) are capable of
      trophoblast-specific expression in human (BeWo) and rat (Rcho-1) choriocarcinoma
      cells. Protein-DNA interactions were identified with oBNC nuclear extracts, and
      mutational analysis of these regions revealed a previously undefined cis-element
      from -102/-123 bp that enhances promoter activity in BeWo cells but not Rcho-1
      cells. Characterization of this region identified the nucleotide sequence CCAGCA
      (-105/-110; o110) as the responsible cis-acting element. Southwestern analysis
      with this element identified a binding protein with an apparent M(r) of
      approximately 41,000. Expression screening of an ovine placental cDNA library
      identified six homologous cDNAs, which shared identity with human (97%) and mouse
      (95%) Pur alpha, a single-stranded DNA binding protein. The Pur alpha-o110
      interaction was confirmed by electrophoretic mobility-supershift assays with oBNC
      and BeWo extracts but was absent with Rcho-1 extracts. Furthermore,
      overexpression of ovine Pur alpha enhanced transactivation of the oPL gene
      proximal promoter in both choriocarcinoma cell lines through this novel cis
      element. This study identified a previously undefined cis-element, which
      interacts with Pur alpha to augment PL gene transcription.

PMID- 14645501
TI  - Proteomic analysis of the systemic immune response of Drosophila.
AB  - Improvements in two-dimensional gel electrophoresis, mass spectrometry, and
      bioinformatics provide new tools to characterize proteins involved in a
      physiological process, such as the immune response of the insect model Drosophila
      melanogaster. Profiling of the proteins present in the hemolymph (insect blood)
      of noninfected flies versus flies infected with bacteria or fungi was performed
      by two-dimensional gel electrophoresis, silver or Coomassie staining, and image
      analysis. Through this differential analysis, more than 70 out of 160 spots were
      up- or down-regulated by at least 5-fold after microbial infection. Coomassie
      staining, in-gel digestion, and database searches yielded the identity of a
      series of proteins that are directly involved in the Drosophila immune system.
      This included proteases, protease inhibitors, and recognition molecules such as
      prophenoloxydase-activating enzymes, serpins, and Gram-negative binding protein
      like. Proteins with a potential function in the immune response were also
      identified, such as an odorant binding protein, peptidylglycine alpha
      hydroxylating monooxygenase, and transferrin, affording new candidates for
      further investigation of innate immune mechanisms. Moreover, several molecules
      resulting from the cleavage of proteins were detected after the fungal infection.
      Altogether, this first differential proteomic analysis of the immune response of
      Drosophila paves the way for the study of proteins affected during innate
      immunity.

PMID- 14645502
TI  - Integration of proteomics and genomics in platelets: a profile of platelet
      proteins and platelet-specific genes.
AB  - Platelets, while anucleate, contain RNA, some of which is translated into protein
      upon activation. Hypothesising that the platelet proteome is reflected in the
      transcriptome, we identified 82 proteins secreted from activated platelets and
      compared these, as well as published proteomic data, to the transcriptional
      profile. We also compared the transcriptome of platelets to other tissues to
      identify platelet-specific genes and used ontology to determine gene categories
      over-represented in platelets. RNA was isolated from highly pure platelet
      preparations for hybridization to Affymetrix oligonucleotide arrays. We
      identified 2,928 distinct messages as being present in platelets. The platelet
      transcriptome was compared with the proteome by relating both to UniGene
      clusters. Platelet proteomic data correlated well with the transcriptome, with
      69% of secreted proteins detectable at the mRNA level, and similar concordance
      was obtained using two published datasets. While many of the most abundant mRNAs
      are for known platelet proteins, messages were detected for proteins not
      previously reported in platelets. Some of these may represent residual
      megakaryocyte messages; however, proteomic analysis confirmed the expression of
      many previously unreported genes in platelets. Transcripts for well-described
      platelet proteins are among the most platelet-specific messages. Ontological
      categories related to signal transduction, receptors, ion channels, and membranes
      are over-represented in platelets, while categories involved in protein synthesis
      are depleted. Despite the absence of gene transcription, the platelet proteome is
      mirrored in the transcriptome. Conversely, transcriptional analysis predicts the
      presence of novel proteins in the platelet. Transcriptional analysis is relevant
      to platelet biology, providing insights into platelet function and the mechanisms
      of platelet disorders.

PMID- 14645503
TI  - Synergistic computational and experimental proteomics approaches for more
      accurate detection of active serine hydrolases in yeast.
AB  - An analysis of the structurally and catalytically diverse serine hydrolase
      protein family in the Saccharomyces cerevisiae proteome was undertaken using two
      independent but complementary, large-scale approaches. The first approach is
      based on computational analysis of serine hydrolase active site structures; the
      second utilizes the chemical reactivity of the serine hydrolase active site in
      complex mixtures. These proteomics approaches share the ability to fractionate
      the complex proteome into functional subsets. Each method identified a
      significant number of sequences, but 15 proteins were identified by both methods.
      Eight of these were unannotated in the Saccharomyces Genome Database at the time
      of this study and are thus novel serine hydrolase identifications. Three of the
      previously uncharacterized proteins are members of a eukaryotic serine hydrolase
      family, designated as Fsh (family of serine hydrolase), identified here for the
      first time. OVCA2, a potential human tumor suppressor, and DYR-SCHPO, a
      dihydrofolate reductase from Schizosaccharomyces pombe, are members of this
      family. Comparing the combined results to results of other proteomic methods
      showed that only four of the 15 proteins were identified in a recent large-scale,
      "shotgun" proteomic analysis and eight were identified using a related, but
      similar, approach (neither identifies function). Only 10 of the 15 were annotated
      using alternate motif-based computational tools. The results demonstrate the
      precision derived from combining complementary, function-based approaches to
      extract biological information from complex proteomes. The chemical proteomics
      technology indicates that a functional protein is being expressed in the cell,
      while the computational proteomics technology adds details about the specific
      type of function and residue that is likely being labeled. The combination of
      synergistic methods facilitates analysis, enriches true positive results, and
      increases confidence in novel identifications. This work also highlights the
      risks inherent in annotation transfer and the use of scoring functions for
      determination of correct annotations.

PMID- 14645504
TI  - The mRNA export factor human Gle1 interacts with the nuclear pore complex protein
      Nup155.
AB  - The protein Gle1 is required for export of mRNAs from the nucleus to the
      cytoplasm in both lower and higher eukaryotic cells. In human (h) cells,
      shuttling of hGle1 between the nucleus and cytoplasm is essential for bulk mRNA
      export. To date, no hGle1-interacting proteins have been reported and the
      mechanism by which hGle1 interacts with the nuclear pore complex (NPC) and
      mediates export is unknown. To identify proteins that can interact with hGle1, a
      genome-wide yeast two-hybrid screen was performed. Three potential hGle1
      interacting partners were isolated, including clones encoding the C-terminal
      region of the NPC protein hNup155. This interaction between hGle1 and full-length
      hNup155 was confirmed in vitro, and deletion analysis identified the N-terminal
      29 residues of hGle1 as the hNup155-binding domain. Experiments in HeLa cells
      confirmed that the nuclear rim localization of the major hGle1 protein variant
      (hGle1B) was dependent on the presence of these 29 N-terminal residues. This
      suggests that this domain of hGle1 is necessary for targeting to the NPC. This
      work also characterizes the first domain in hNup155, a 177 C-terminal amino acid
      span that binds to hGle1. The mutual interaction between hGle1 and the
      symmetrically distributed nuclear pore protein Nup155 suggests a model in which
      hGle1's association with hNup155 may represent a step in the Gle1-mediated mRNA
      export pathway.

PMID- 14645505
TI  - Assembly of 48S translation initiation complexes from purified components with
      mRNAs that have some base pairing within their 5' untranslated regions.
AB  - The reconstitution of translation initiation complexes from purified components
      is a reliable approach to determine the complete set of essential canonical
      initiation factors and auxiliary proteins required for the 40S ribosomal subunit
      to locate the initiation codon on individual mRNAs. Until now, it has been
      successful mostly for formation of 48S translation initiation complexes with
      viral IRES elements. Among cap-dependent mRNAs, only globin mRNAs and transcripts
      with artificial 5' leaders were amenable to this assembly. Here, with modified
      conditions for the reconstitution, 48S complexes have been successfully assembled
      with the 5' UTR of beta-actin mRNA (84 nucleotides) and the tripartite leader of
      adenovirus RNAs (232 nucleotides), though the latter has been able to use only
      the scanning rather then the shunting model of translation initiation with
      canonical initiation factors. We show that initiation factor 4B is essential for
      mRNAs that have even a rather moderate base pairing within their 5' UTRs (with
      the cumulative stability of the secondary structure within the entire 5' UTR < 
      13 kcal/mol) and not essential for beta-globin mRNA. A recombinant eIF4B poorly
      substitutes for the native factor. The 5' UTRs with base-paired G residues reveal
      a very sharp dependence on the eIF4B concentration to form the 48S complex. The
      data suggest that even small variations in concentration or activity of eIF4B in
      mammalian cells may differentially affect the translation of different classes of
      cap-dependent cellular mRNAs.

PMID- 14645506
TI  - STAT5 and Oct-1 form a stable complex that modulates cyclin D1 expression.
AB  - Signal transducer and activator of transcription 5 (STAT5) is activated by
      numerous cytokines that control blood cell development. STAT5 was also shown to
      actively participate in leukemogenesis. Among the target genes involved in cell
      growth, STAT5 had been shown to activate cyclin D1 gene expression. We now show
      that thrombopoietin-dependent activation of the cyclin D1 promoter depends on the
      integrity of a new bipartite proximal element that specifically binds STAT5A and 
      B transcription factors. We demonstrate that the stable recruitment of STAT5 to
      this element in vitro requires the integrity of an adjacent octamer element that
      constitutively binds the ubiquitous POU homeodomain protein Oct-1. We observe
      that cytokine-activated STAT5 and Oct-1 form a unique complex with the cyclin D1
      promoter sequence. We find that STAT5 interacts with Oct-1 in vivo, following
      activation by different cytokines in various cellular contexts. This interaction
      involves a small motif in the carboxy-terminal region of STAT5 which, remarkably,
      is similar to an Oct-1 POU-interacting motif present in two well-known partners
      of Oct-1, namely, OBF-1/Bob and SNAP190. Our data offer new insights into the
      transcriptional regulation of the key cell cycle regulator cyclin D1 and
      emphasize the active roles of both STAT5 and Oct-1 in this process.

PMID- 14645507
TI  - Human beta-globin locus control region HS5 contains CTCF- and developmental stage
      dependent enhancer-blocking activity in erythroid cells.
AB  - The human beta-globin locus contains five developmentally regulated beta-type
      globin genes. All five genes depend on the locus control region (LCR), located at
      the 5' end of the locus, for abundant globin gene transcription. The LCR is
      composed of five DNase I-hypersensitive sites (HSs), at least a subset of which
      appear to cooperate to form a holocomplex in activating genes within the locus.
      We previously tested the requirement for proper LCR polarity by inverting it in
      human beta-globin yeast artificial chromosome transgenic mice and observed
      reduced expression of all the beta-type globin genes regardless of developmental
      stage. This phenotype clearly demonstrated an orientation-dependent activity of
      the LCR, although the mechanistic basis for the observed activity was obscure.
      Here, we describe genetic evidence demonstrating that human HS5 includes enhancer
      blocking (insulator) activity that is both CTCF and developmental stage
      dependent. Curiously, we also observed an attenuating activity in HS5 that was
      specific to the epsilon-globin gene at the primitive stage and was independent of
      the HS5 CTCF binding site. These observations demonstrate that the phenotype
      observed in the LCR-inverted locus was in part attributable to placing the HS5
      insulator between the LCR HS enhancers (HS1 to HS4) and the promoter of the beta
      globin gene.

PMID- 14645508
TI  - Genomic imprinting controls matrix attachment regions in the Igf2 gene.
AB  - Genomic imprinting at the Igf2/H19 locus originates from allele-specific DNA
      methylation, which modifies the affinity of some proteins for their target
      sequences. Here, we show that AT-rich DNA sequences located in the vicinity of
      previously characterized differentially methylated regions (DMRs) of the
      imprinted Igf2 gene are conserved between mouse and human. These sequences have
      all the characteristics of matrix attachment regions (MARs), which are known as
      versatile regulatory elements involved in chromatin structure and gene
      expression. Combining allele-specific nuclear matrix binding assays and real-time
      PCR quantification, we show that retention of two of these Igf2 MARs (MAR0 and
      MAR2) in the nuclear matrix fraction depends on the tissue and is specific to the
      paternal allele. Furthermore, on this allele, the Igf2 MAR2 is functionally
      linked to the neighboring DMR2 while, on the maternal allele, it is controlled by
      the imprinting-control region. Our work clearly demonstrates that genomic
      imprinting controls matrix attachment regions in the Igf2 gene.

PMID- 14645509
TI  - Involvement of the DNA repair protein hHR23 in p53 degradation.
AB  - The stability of the tumor suppressor protein p53 is regulated via the ubiquitin
      proteasome-dependent proteolytic pathway. Like most substrates of this pathway,
      p53 is modified by the attachment of polyubiquitin chains prior to proteasome
      mediated degradation. However, the mechanism(s) involved in the delivery of
      polyubiquitylated p53 molecules to the proteasome are currently unclear. Here, we
      show that the human DNA repair protein hHR23 binds to polyubiquitylated p53 via
      its carboxyl-terminal ubiquitin-associated (Uba) domain shielding p53 from
      deubiquitylation in vitro and in vivo. In addition, downregulation of hHR23
      expression within cells by RNA interference results in accumulation of p53. Since
      the Ubl domain of hHR23 has been shown to interact with the 26S proteasome, we
      propose that hHR23 is intrinsically involved in the delivery of polyubiquitylated
      p53 molecules to the proteasome. In this model, the Uba domain of hHR23 binds to
      polyubiquitin chains formed on p53 and protects them from deubiquitylation, while
      the Ubl domain delivers the polyubiquitylated p53 molecules to the proteasome.

PMID- 14645510
TI  - Requirement of PDZ-containing proteins for cell cycle regulation and
      differentiation in the mouse lens epithelium.
AB  - The roles of PDZ domain-containing proteins such as Dlg and Scrib have been well
      described for Drosophila; however, their requirement for mammalian development is
      poorly understood. Here we show that Dlg, Scrib, MAGI1, MAGI3, and MPDZ are
      expressed in the mouse ocular lens. We demonstrate that the increase in
      proliferation and defects in cellular adhesion and differentiation observed in
      epithelia of lenses that express E6, a viral oncoprotein that can bind to several
      PDZ proteins, including the human homologs of Dlg and Scrib, is dependent on E6's
      ability to bind these proteins via their PDZ domains. Analyses of lenses from
      mice carrying an insertional mutation in Dlg (dlg(gt)) show increased
      proliferation and proliferation in spatially inappropriate regions of the lens, a
      phenotype similar to that of lenses expressing E6. The results from this study
      indicate that multiple PDZ domain-containing proteins, including Dlg and Scrib,
      may be required for maintaining the normal pattern of growth and differentiation
      in the lens. Furthermore, the phenotypic similarities among the Drosophila dlg
      mutant, the lenses of dlg(gt) mice, and the lenses of E6 transgenic mice suggest
      that Dlg may have a conserved function in regulating epithelial cell growth and
      differentiation across species.

PMID- 14645511
TI  - Mutation of a conserved hydrophobic patch prevents incorporation of ZP3 into the
      zona pellucida surrounding mouse eggs.
AB  - Three glycoproteins (ZP1, ZP2, and ZP3) are synthesized in growing mouse oocytes
      and secreted to form an extracellular zona pellucida that mediates sperm binding
      and fertilization. Each has a signal peptide to direct it into a secretory
      pathway, a "zona" domain implicated in matrix polymerization and a transmembrane
      domain from which the ectodomain must be released. Using confocal microscopy and
      enhanced green fluorescent protein (EGFP), the intracellular trafficking of ZP3
      was observed in growing mouse oocytes. Replacement of the zona domain with EGFP
      did not prevent secretion of ZP3, suggesting the presence of trafficking signals
      and a cleavage site in the carboxyl terminus. Analysis of linker-scanning
      mutations of a ZP3-EGFP fusion protein in transient assays and in transgenic mice
      identified an eight-amino-acid hydrophobic region required for secretion and
      incorporation into the zona pellucida. The hydrophobic patch is conserved among
      mouse zona proteins and lies between a potential proprotein convertase (furin)
      cleavage site and the transmembrane domain. The cleavage site that releases the
      ectodomain from the transmembrane domain was defined by mass spectrometry of
      native zonae pellucidae and lies N-terminal to a proprotein convertase site that
      is distinct from the hydrophobic patch.

PMID- 14645512
TI  - Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport
      impedes hematopoietic differentiation and contributes to leukemogenesis.
AB  - The eukaryotic translation initiation factor 4E (eIF4E) acts as both a key
      translation factor and as a promoter of nucleocytoplasmic transport of specific
      transcripts. Traditionally, its transformation capacity in vivo is attributed to
      its role in translation initiation in the cytoplasm. Here, we demonstrate that
      elevated eIF4E impedes granulocytic and monocytic differentiation. Our subsequent
      mutagenesis studies indicate that this block is a result of dysregulated eIF4E
      dependent mRNA transport. These studies indicate that the RNA transport function
      of eIF4E could contribute to leukemogenesis. We extended our studies to provide
      the first evidence that the nuclear transport function of eIF4E contributes to
      human malignancy, specifically in a subset of acute and chronic myelogenous
      leukemia patients. We observe an increase in eIF4E-dependent cyclin D1 mRNA
      transport and a concomitant increase in cyclin D1 protein levels. The aberrant
      nuclear function of eIF4E is due to abnormally large eIF4E bodies and the loss of
      regulation by the proline-rich homeodomain PRH. We developed a novel tool to
      modulate this transport activity. The introduction of IkappaB, the repressor of
      NF-kappaB, leads to suppression of eIF4E, elevation of PRH, reorganization of
      eIF4E nuclear bodies, and subsequent downregulation of eIF4E-dependent mRNA
      transport. Thus, our findings indicate that this nuclear function of eIF4E can
      contribute to leukemogenesis by promoting growth and by impeding differentiation.

PMID- 14645513
TI  - The LMO2 T-cell oncogene is activated via chromosomal translocations or
      retroviral insertion during gene therapy but has no mandatory role in normal T
      cell development.
AB  - The LMO2 gene encodes a LIM-only protein and is a target of chromosomal
      translocations in human T-cell leukemia. Recently, two X-SCID patients treated by
      gene therapy to rescue T-cell lymphopoiesis developed T-cell leukemias with
      retroviral insertion into the LMO2 gene causing clonal T-cell proliferation. In
      view of the specificity of LMO2 in T-cell tumorigenesis, we investigated a
      possible role for Lmo2 in T-lymphopoiesis, using conditional knockout of mouse
      Lmo2 with loxP-flanked Lmo2 and Cre recombinase alleles driven by the promoters
      of the lymphoid-specific genes Rag1, CD19, and Lck. While efficient deletion of
      Lmo2 was observed, even in the earliest detectable lymphoid cell progenitors of
      the bone marrow, there was no disturbance of lymphopoiesis in either T- or B-cell
      lineages, and in contrast to Lmo2 transgenic mice, there were normal
      distributions of CD4- CD- thymocytes. We conclude that there is no mandatory role
      for LMO2 in lymphoid development, implying that its specific role in T-cell
      tumorigenesis results from a reprogramming of gene expression after enforced
      expression in T-cell precursors.

PMID- 14645514
TI  - Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant
      protein C transcription.
AB  - Surfactant protein C (SP-C; Sftpc) gene expression is restricted to pulmonary
      type II epithelial cells. The proximal SP-C promoter region contains critical
      binding sites for nuclear factor I (NFI) and thyroid transcription factor 1 (TTF
      1; also called Nkx2.1). To test the hypothesis that NFI isoforms interact with
      TTF-1 to differentially regulate SP-C transcription, we performed transient
      transfection assays in JEG-3 cells, a choriocarcinoma cell line with negligible
      endogenous NFI or TTF-1 activity. Cotransfection of NFI family members with TTF-1
      induced synergistic activation of the SP-C promoter that was further enhanced by
      p300. TTF-1 directly interacts with the conserved DNA binding and dimerization
      domain of all NFI family members in coimmunoprecipitation and mammalian two
      hybrid experiments. To determine whether SP-C expression is regulated by NFI in
      vivo, a chimeric fusion protein containing the DNA binding and dimerization
      domain of NFI-A and the Drosophila engrailed transcriptional repression domain
      (NFIen) was conditionally expressed in mice under control of a doxycycline
      inducible transgene. Induction of NFIen in a subset of type II cells inhibited SP
      C gene expression without affecting expression of TTF-1 in doxycycline-treated
      double-transgenic mice. Taken together, these findings support the hypothesis
      that NFI family members interact with TTF-1 to regulate type II cell function.

PMID- 14645515
TI  - REST/NRSF-interacting LIM domain protein, a putative nuclear translocation
      receptor.
AB  - The transcriptional repressor REST/NRSF (RE-1 silencing transcription
      factor/neuron-restrictive silencer factor) and the transcriptional regulator
      REST4 share an N-terminal zinc finger domain structure involved in nuclear
      targeting. Using this domain as bait in a yeast two-hybrid screen, a novel
      protein that contains three LIM domains, putative nuclear localization sequences,
      protein kinase A phosphorylation sites, and a CAAX prenylation motif was
      isolated. This protein, which is localized around the nucleus, is involved in
      determining the nuclear localization of REST4 and REST/NRSF. We propose the name
      RILP, for REST/NRSF-interacting LIM domain protein, to label this novel protein.
      RILP appears to serve as a nuclear receptor for REST/NRSF, REST4, and possibly
      other transcription factors.

PMID- 14645516
TI  - Anoxic fibroblasts activate a replication checkpoint that is bypassed by E1a.
AB  - Little is known about cell cycle regulation in hypoxic cells, despite its
      significance. We utilized an experimentally tractable model to study the
      proliferative responses of rat fibroblasts when rendered hypoxic (0.5% oxygen) or
      anoxic (<0.01% oxygen). Hypoxic cells underwent G1 arrest, whereas anoxic cells
      also demonstrated S-phase arrest due to suppression of DNA initiation. Upon
      reoxygenation, only those cells arrested in G1 were able to resume proliferation.
      The oncoprotein E1a induced p53-independent apoptosis in anoxic cells, which when
      suppressed by Bcl-2 permitted proliferation despite anoxia. E1a expression led to
      marked increases in the transcription factor E2F, and overexpression of E2F-1
      allowed proliferation in hypoxic cells, although it had minimal effect on the
      anoxic suppression of DNA initiation. We thus demonstrate two distinct cell cycle
      responses to low oxygen and suggest that alterations that lead to increased E2F
      can overcome hypoxic G1 arrest but that additional alterations, promoted by E1a
      expression, are necessary for neoplastic cells to proliferate despite anoxia.

PMID- 14645517
TI  - Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to
      Drosophila S59/slouch: evidence for positive and negative autoregulation.
AB  - Homeobox gene transcription factors direct multiple functions during development.
      They are involved in early patterning of the embryo as well as cell
      specification, cell differentiation, and organogenesis. Here we describe a
      previously uncharacterized murine homeobox gene, Sax2, that shows high similarity
      to the Drosophila S59/slouch and murine Sax1 genes. We show that Sax2 gene
      expression occurs early during embryogenesis in the midbrain, the midbrain
      hindbrain boundary, the ventral neural tube, the developing eye, and the apical
      ectodermal ridge of the limb. To determine the role of Sax2 during development,
      we generated a knockout mouse line by replacing part of the Sax2 coding sequences
      with the lacZ gene. The Sax2 null allele mutants exhibit a strong phenotype
      indicated by growth retardation starting immediately after birth and leading to
      premature death within the first 3 weeks postnatal. Intriguingly, our studies
      also demonstrated a striking autoregulation of the Sax2 gene in both positive-
      and negative-feedback mechanisms depending on the specific cell type expressing
      Sax2.

PMID- 14645518
TI  - A sequence motif within trypanosome precursor tRNAs influences abundance and
      mitochondrial localization.
AB  - Trypanosoma brucei lacks mitochondrial genes encoding tRNAs and must import
      nuclearly encoded tRNAs from the cytosol. The mechanism and specificity of this
      process remain unclear. We have identified a unique sequence motif, YGG(C/A)RRC,
      upstream of the genes encoding mitochondrially localized tRNAs in T. brucei. Both
      in vitro import studies and in vivo transfection studies indicate that deletion
      of the YGG(C/A)RRC sequence alters mitochondrial localization of tRNA(Leu), and
      in vivo studies also show a decrease in the cellular abundance of tRNA(Leu).
      These studies provide direct evidence for cis-acting RNA motifs within precursor
      tRNAs that facilitate the selection of tRNAs for mitochondrial import in
      trypanosomes. Furthermore, we found that mutations to the YGG(C/A)RRC sequence
      also altered the intracellular distribution of other endogenous tRNAs, suggesting
      a general role for this sequence in tRNA trafficking in trypanosomes.

PMID- 14645519
TI  - Role played by microphthalmia transcription factor phosphorylation and its Zip
      domain in its transcriptional inhibition by PIAS3.
AB  - Mutation of microphthalmia transcription factor (MITF) results in deafness, bone
      loss, small eyes, and poorly pigmented eyes and skin. A search for MITF
      associated proteins, using a mast cell library that was screened with a construct
      that encodes the basic helix-loop-helix leucine zipper (Zip) domain of MITF,
      resulted in the isolation of the STAT3 inhibitor, PIAS3. PIAS3 functions in vivo
      as a key molecule in suppressing the transcriptional activity of MITF. Here, we
      report that the Zip domain is the region of MITF that is involved in the direct
      interaction between MITF and PIAS3. Additionally, we investigated the effect of
      phosphorylation of MITF on its interaction with PIAS3. We found that
      phosphorylation of MITF on serines in positions 73 and 409 plays an important
      role in its association with PIAS3. This effect was profound with phosphorylation
      on Ser409, which significantly reduced the inhibitory effect of PIAS3 on MITF and
      also modulated the transcriptional activity of MITF. Thus, phosphorylation of
      MITF could be considered a fine, and alternative, tuning of its transcriptional
      machinery.

PMID- 14645520
TI  - Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic
      protein-induced transcription.
AB  - Smad6 and Smad7 are inhibitory Smads induced by transforming growth factor beta
      Smad signal transduction pathways in a negative-feedback mechanism. Previously it
      has been thought that inhibitory Smads bind to the type I receptor and block the
      phosphorylation of receptor-activated Smads, thereby inhibiting the initiation of
      Smad signaling. Conversely, few studies have suggested the possible nuclear
      functions of inhibitory Smads. Here, we present compelling evidence demonstrating
      that Smad6 repressed bone morphogenetic protein-induced Id1 transcription through
      recruiting transcriptional corepressor C-terminal binding protein (CtBP). A
      consensus CtBP-binding motif, PLDLS, was identified in the linker region of
      Smad6. Our findings show that mutation in the motif abolished the Smad6 binding
      to CtBP and subsequently its repressor activity of transcription. We conclude
      that the nuclear functions and physical interaction of Smad6 and CtBP provide a
      novel mechanism for the transcriptional regulation by inhibitory Smads.

PMID- 14645521
TI  - Recapitulation of the effects of the human papillomavirus type 16 E7 oncogene on
      mouse epithelium by somatic Rb deletion and detection of pRb-independent effects
      of E7 in vivo.
AB  - Although the human papillomavirus (HPV) E7 oncogene is known to contribute to the
      development of human cervical cancer, the mechanisms of its carcinogenesis are
      poorly understood. The first identified and most recognized function of E7 is its
      binding to and inactivation of the retinoblastoma tumor suppressor (pRb), but at
      least 18 other biological activities have also been reported for E7. Thus, it
      remains unclear which of these many activities contribute to the oncogenic
      potential of E7. We used a Cre-lox system to abolish pRb expression in the
      epidermis of transgenic mice and compared the outcome with the effects of E7
      expression in the same tissue at early ages. Mice lacking pRb in epidermis showed
      epithelial hyperplasia, aberrant DNA synthesis, and improper differentiation. In
      addition, Rb-deleted epidermis (i.e., epidermis composed of cells with Rb
      deleted) exhibited centrosomal abnormalities and failed to arrest the cell cycle
      in response to ionizing radiation. Transgenic mice expressing E7 in skin display
      the same range of phenotypes. In sum, few differences were detected between Rb
      deleted epidermis and E7-expressing epidermis in young mice. However, when both
      E7 was expressed and Rb was deleted in the same tissue, increased hyperplasia and
      dysplasia were observed. These findings indicate that inactivation of the Rb
      pathway can largely account for E7's phenotypes at an early age, but that pRb
      independent activities of E7 are detectable in vivo.

PMID- 14645522
TI  - Transcriptional activation of the cyclin A gene by the architectural
      transcription factor HMGA2.
AB  - The HMGA2 protein belongs to the HMGA family of architectural transcription
      factors, which play an important role in chromatin organization. HMGA proteins
      are overexpressed in several experimental and human tumors and have been
      implicated in the process of neoplastic transformation. Hmga2 knockout results in
      the pygmy phenotype in mice and in a decreased growth rate of embryonic
      fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show
      that HMGA2 associates with the E1A-regulated transcriptional repressor p120(E4F),
      interfering with p120(E4F) binding to the cyclin A promoter. Ectopic expression
      of HMGA2 results in the activation of the cyclin A promoter and induction of the
      endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments
      show that HMGA2 associates with the cyclin A promoter only when the gene is
      transcriptionally activated. These data identify the cyclin A gene as a cellular
      target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent
      cell cycle regulation.

PMID- 14645523
TI  - Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila
      melanogaster.
AB  - The eIF4E-binding proteins (4E-BPs) interact with translation initiation factor
      4E to inhibit translation. Their binding to eIF4E is reversed by phosphorylation
      of several key Ser/Thr residues. In Drosophila, S6 kinase (dS6K) and a single 4E
      BP (d4E-BP) are phosphorylated via the insulin and target of rapamycin (TOR)
      signaling pathways. Although S6K phosphorylation is independent of
      phosphoinositide 3-OH kinase (PI3K) and serine/threonine protein kinase Akt, that
      of 4E-BP is dependent on PI3K and Akt. This difference prompted us to examine the
      regulation of d4E-BP in greater detail. Analysis of d4E-BP phosphorylation using
      site-directed mutagenesis and isoelectric focusing-sodium dodecyl sulfate
      polyacrylamide gel electrophoresis indicated that the regulatory interplay
      between Thr37 and Thr46 of d4E-BP is conserved in flies and that phosphorylation
      of Thr46 is the major phosphorylation event that regulates d4E-BP activity. We
      used RNA interference (RNAi) to target components of the PI3K, Akt, and TOR
      pathways. RNAi experiments directed at components of the insulin and TOR
      signaling cascades show that d4E-BP is phosphorylated in a PI3K- and Akt
      dependent manner. Surprisingly, RNAi of dAkt also affected insulin-stimulated
      phosphorylation of dS6K, indicating that dAkt may also play a role in dS6K
      phosphorylation.

PMID- 14645524
TI  - Calpain 3 is activated through autolysis within the active site and lyses
      sarcomeric and sarcolemmal components.
AB  - Calpain 3 (Capn3) is known as the skeletal muscle-specific member of the
      calpains, a family of intracellular nonlysosomal cysteine proteases. This
      enigmatic protease has many unique features among the calpain family and,
      importantly, mutations in Capn3 have been shown to be responsible for limb girdle
      muscular dystrophy type 2A. Here we demonstrate that the Capn3 activation
      mechanism is similar to the universal activation of caspases and corresponds to
      an autolysis within the active site of the protease. We undertook a search for
      substrates in immature muscle cells, as several lines of evidence suggest that
      Capn3 is mostly in an inactive state in muscle and needs a signal to be
      activated. In this model, Capn3 proteolytic activity leads to disruption of the
      actin cytoskeleton and disorganization of focal adhesions through cleavage of
      several endogenous proteins. In addition, we show that titin, a previously
      identified Capn3 partner, and filamin C are further substrates of Capn3. Finally,
      we report that Capn3 colocalizes in vivo with its substrates at various sites
      along cytoskeletal structures. We propose that Capn3-mediated cleavage produces
      an adaptive response of muscle cells to external and/or internal stimuli,
      establishing Capn3 as a muscle cytoskeleton regulator.

PMID- 14645525
TI  - Global control of histone modification by the anaphase-promoting complex.
AB  - Acetylation and phosphorylation of the amino-terminal tails of the core histones
      fluctuate on a global scale in concert with other major events in chromosome
      metabolism. A ubiquitin ligase, the anaphase-promoting complex (APC), controls
      events in chromosome metabolism such as sister chromatid cohesion and may
      regulate H3 phosphorylation by targeting Aurora A, one of several S10-directed H3
      kinases in vertebrate cells, for destruction by the proteasome. Our analysis of
      apc10Delta and apc11(ts) loss-of-function mutants reveals that the APC controls
      the global level of H3 S10 phosphorylation in cycling yeast cells. Surprisingly,
      it also regulates dephosphorylation of H3 and global deacetylation of H2B, H3,
      and H4 during exit from the cell cycle into G(0). Genetic, biochemical, and
      microarray analyses suggest that APC-dependent cell cycle control of H3
      phosphorylation is exerted at the level of an Aurora H3 kinase, Ipl1p, while APC
      dependent transcriptional induction of GLC7, an essential H3 phosphatase,
      contributes to sustained H3 dephosphorylation upon cell cycle withdrawal.
      Collectively, our results establish that core histone acetylation state and H3
      phosphorylation are physiologically regulated by the APC and suggest a model in
      which global reconfiguration of H3 phosphorylation state involves APC-dependent
      control of both an H3 kinase and a conserved phosphatase.

PMID- 14645526
TI  - Generation and analysis of Siah2 mutant mice.
AB  - Siah proteins function as E3 ubiquitin ligase enzymes to target the degradation
      of diverse protein substrates. To characterize the physiological roles of Siah2,
      we have generated and analyzed Siah2 mutant mice. In contrast to Siah1a knockout
      mice, which are growth retarded and exhibit defects in spermatogenesis, Siah2
      mutant mice are fertile and largely phenotypically normal. While previous studies
      implicate Siah2 in the regulation of TRAF2, Vav1, OBF-1, and DCC, we find that a
      variety of responses mediated by these proteins are unaffected by loss of Siah2.
      However, we have identified an expansion of myeloid progenitor cells in the bone
      marrow of Siah2 mutant mice. Consistent with this, we show that Siah2 mutant bone
      marrow produces more osteoclasts in vitro than wild-type bone marrow. The
      observation that combined Siah2 and Siah1a mutation causes embryonic and neonatal
      lethality demonstrates that the highly homologous Siah proteins have partially
      overlapping functions in vivo.

PMID- 14645527
TI  - Ubiquitin depletion as a key mediator of toxicity by translational inhibitors.
AB  - Cycloheximide acts at the large subunit of the ribosome to inhibit translation.
      Here we report that ubiquitin levels are critical for the survival of
      Saccharomyces cerevisiae cells in the presence of cycloheximide: ubiquitin
      overexpression confers resistance to cycloheximide, while a reduced ubiquitin
      level confers sensitivity. Consistent with these findings, ubiquitin is unstable
      in yeast (t(1/2) = 2 h) and is rapidly depleted upon cycloheximide treatment.
      Cycloheximide does not noticeably enhance ubiquitin turnover, but serves
      principally to block ubiquitin synthesis. Cycloheximide also induces UBI4, the
      polyubiquitin gene. The cycloheximide-resistant phenotype of ubiquitin
      overexpressors is also characteristic of partial-loss-of-function proteasome
      mutants. Ubiquitin is stabilized in these mutants, which may account for their
      cycloheximide resistance. Previous studies have reported that ubiquitin is
      destabilized in the absence of Ubp6, a proteasome-associated deubiquitinating
      enzyme, and that ubp6 mutants are hypersensitive to cycloheximide. Consistent
      with the model that cycloheximide-treated cells are ubiquitin deficient, the
      cycloheximide sensitivity of ubp6 mutants can be rescued either by ubiquitin
      overexpression or by mutations in proteasome subunit genes. These results also
      show that ubiquitin wasting in ubp6 mutants is proteasome mediated. Ubiquitin
      overexpression rescued cells from additional translational inhibitors such as
      anisomycin and hygromycin B, suggesting that ubiquitin depletion may constitute a
      widespread mechanism for the toxicity of translational inhibitors.

PMID- 14645528
TI  - Mitotic cyclins regulate telomeric recombination in telomerase-deficient yeast
      cells.
AB  - Telomerase-deficient mutants of Saccharomyces cerevisiae can survive death by
      senescence by using one of two homologous recombination pathways. The Rad51
      pathway amplifies the subtelomeric Y' sequences, while the Rad50 pathway
      amplifies the telomeric TG(1-3) repeats. Here we show that telomerase-negative
      cells require Clb2 (the major B-type cyclin in this organism), in association
      with Cdc28 (Cdk1), to generate postsenescence survivors at a normal rate. The
      Rad50 pathway was more sensitive to the absence of Clb2 than the Rad51 pathway.
      We also report that telomerase RAD50 RAD51 triple mutants still generated
      postsenescence survivors. This novel Rad50- and Rad51-independent pathway of
      telomeric recombination also appeared to be controlled by Clb2. In telomerase
      positive cells, a synthetic growth defect between mutations in CLB2 and RAD50 or
      in its partners in the conserved MRX complex, MRE11 and XRS2, was observed. This
      genetic interaction was independent of Mre11 nuclease activity but was dependent
      on a DNA repair function. The present data reveal an unexpected role of
      Cdc28/Clb2 in telomeric recombination during telomerase-independent maintenance
      of telomeres. They also uncover a functional interaction between Cdc28/Clb2 and
      MRX during the control of the mitotic cell cycle.

PMID- 14645529
TI  - The replication fork barrier site forms a unique structure with Fob1p and
      inhibits the replication fork.
AB  - The replication fork barrier site (RFB) is an approximately 100-bp DNA sequence
      located near the 3' end of the rRNA genes in the yeast Saccharomyces cerevisiae.
      The gene FOB1 is required for this RFB activity. FOB1 is also necessary for
      recombination in the ribosomal DNA (rDNA), including increase and decrease of
      rDNA repeat copy number, production of extrachromosomal rDNA circles, and
      possibly homogenization of the repeats. Despite the central role that Foblp plays
      in both replication fork blocking and rDNA recombination, the molecular mechanism
      by which Fob1p mediates these activities has not been determined. Here, I show by
      using chromatin immunoprecipitation, gel shift, footprinting, and atomic force
      microscopy assays that Fob1p directly binds to the RFB. Fob1p binds to two
      separated sequences in the RFB. A predicted zinc finger motif in Fob1p was shown
      to be essential for the RFB binding, replication fork blocking, and rDNA
      recombination activities. The RFB seems to wrap around Fob1p, and this wrapping
      structure may be important for function in the rDNA repeats.

PMID- 14645530
TI  - Characterization of Sleeping Beauty transposition and its application to genetic
      screening in mice.
AB  - The use of mutant mice plays a pivotal role in determining the function of genes,
      and the recently reported germ line transposition of the Sleeping Beauty (SB)
      transposon would provide a novel system to facilitate this approach. In this
      study, we characterized SB transposition in the mouse germ line and assessed its
      potential for generating mutant mice. Transposition sites not only were clustered
      within 3 Mb near the donor site but also were widely distributed outside this
      cluster, indicating that the SB transposon can be utilized for both region
      specific and genome-wide mutagenesis. The complexity of transposition sites in
      the germ line was high enough for large-scale generation of mutant mice. Based on
      these initial results, we conducted germ line mutagenesis by using a gene trap
      scheme, and the use of a green fluorescent protein reporter made it possible to
      select for mutant mice rapidly and noninvasively. Interestingly, mice with
      mutations in the same gene, each with a different insertion site, were obtained
      by local transposition events, demonstrating the feasibility of the SB transposon
      system for region-specific mutagenesis. Our results indicate that the SB
      transposon system has unique features that complement other mutagenesis
      approaches.

PMID- 14645531
TI  - Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific
      kinase-defective isoform.
AB  - WNK1 is a serine-threonine kinase, the expression of which is affected in
      pseudohypoaldosteronism type II, a Mendelian form of arterial hypertension. We
      characterized human WNK1 transcripts to determine the molecular mechanisms
      governing WNK1 expression. We report the presence of two promoters generating two
      WNK1 isoforms with a complete kinase domain. Further variations are achieved by
      the use of two polyadenylation sites and tissue-specific splicing. We also
      determined the structure of a kidney-specific isoform regulated by a third
      promoter and starting at a novel exon. This transcript is kinase defective and
      has a predominant expression in the kidney compared to the other WNK1 isoforms,
      with, furthermore, a highly restricted expression profile in the distal
      convoluted tubule. We confirmed that the ubiquitous and kidney-specific promoters
      are functional in several cells lines and identified core promoters and
      regulatory elements. In particular, a strong enhancer element upstream from the
      kidney-specific exon seems specific to renal epithelial cells. Thus, control of
      human WNK1 gene expression of kinase-active or -deficient isoforms is mediated
      predominantly through the use of multiple transcription initiation sites and
      tissue-specific regulatory elements.

PMID- 14645532
TI  - Myocardin expression is regulated by Nkx2.5, and its function is required for
      cardiomyogenesis.
AB  - Nkx2.5 (also known as Csx) is an evolutionarily conserved cardiac transcription
      factor of the homeobox gene family. Nkx2.5 is required for early heart
      development, since Nkx2.5-null mice die before completion of cardiac looping. To
      identify genes regulated by Nkx2.5 in the developing heart, we performed
      subtractive hybridization by using RNA isolated from wild-type and Nkx2.5-null
      hearts at embryonic day 8.5. We isolated a mouse cDNA encoding myocardin A, which
      is an alternative spliced isoform of myocardin and the most abundant isoform in
      the heart from embryo to adult. The expression of myocardin A and myocardin was
      markedly downregulated in Nkx2.5-null mouse hearts. Transient-cotransfection
      analysis showed that Nkx2.5 transactivates the myocardin promoter. Inhibition of
      myocardin function in the teratocarcinoma cell line P19CL6 prevented
      differentiation into cardiac myocytes after dimethyl sulfoxide treatment.
      Myocardin A transactivated the promoter of the atrial natriuretic factor gene
      through the serum response element, which was augmented by bone morphogenetic
      protein 2 and transforming growth factor beta-activated kinase 1. These results
      suggest that myocardin expression is regulated by Nkx2.5 and that its function is
      required for cardiomyogenesis.

PMID- 14645533
TI  - Transcriptional regulation of cyclooxygenase 2 by bradykinin and interleukin
      1beta in human airway smooth muscle cells: involvement of different promoter
      elements, transcription factors, and histone h4 acetylation.
AB  - Bradykinin and interleukin-1beta (IL-1beta) induce cyclooxygenase 2 (COX-2) in
      human airway smooth muscle cells. Here we extended our study to explore the gene
      transcriptional regulation. By transfection with various COX-2 promoter reporter
      constructs, we found that the bp -327-to-+59 promoter region was essential for
      COX-2 gene transcription by bradykinin and IL-1beta and that the cyclic AMP
      response element (CRE) was critical in bradykinin-induced transcription, whereas
      nuclear factor IL-6 and CRE and, to a lesser extent, nuclear factor-kappaB (NF
      kappaB) were involved in IL-1beta-induced transcription. An electrophoretic
      mobility shift assay revealed that both bradykinin and IL-1beta elicited CRE
      binding protein-1 (CREB-1) binding, and IL-1beta also elicited CCAAT/enhancer
      binding protein beta and NF-kappaB binding to their respective elements in the
      COX-2 promoter. These transcription factors were associated with the COX-2
      promoter, which was dynamically linked to different patterns of histone H4
      acetylation by bradykinin and IL-1beta, as demonstrated by chromatin
      immunoprecipitation. We also revealed that endogenous prostaglandin E(2) was
      critical in bradykinin-induced COX-2 transcription initiation and involved in IL
      1beta-induced COX-2 transcription at a latter stage. Our result provide the first
      evidence that COX-2 transcriptional regulation by different stimuli involves
      different promoter elements and transcription factors and is associated with
      chromatin remodeling after selective histone H4 acetylation in a stimulus
      specific manner.

PMID- 14645534
TI  - While K-ras is essential for mouse development, expression of the K-ras 4A splice
      variant is dispensable.
AB  - In mammals, the three classical ras genes encode four highly homologous proteins,
      N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B. Previous studies have shown that
      K-ras is essential for mouse development and that while K-ras 4A and 4B are
      expressed during development, K-ras 4A expression is regulated temporally and
      spatially and occurs in adult kidney, intestine, stomach, and liver. In the
      present study, the pattern of K-ras 4A expression was examined in a wide range of
      wild-type adult mouse tissues, and gene targeting was used to generate K-ras 4A
      deficient mice to examine its role in development. It was found that K-ras 4A is
      also expressed in uterus, lung, pancreas, salivary glands, seminal vesicles, bone
      marrow cells, and cecum, where it was the major K-Ras isoform expressed. Mating
      between K-ras(tmDelta4A/+) mice produced viable K-ras(tmDelta4A/tmDelta4A)
      offspring with the expected Mendelian ratios of inheritance, and these mice
      expressed the K-ras 4B splice variant only. K-ras(tmDelta4A/tmDelta4A) mice were
      fertile and showed no histopathological abnormalities on inbred (129/Ola) or
      crossbred (129/Ola x C57BL/6) genetic backgrounds. The results demonstrate that K
      Ras 4A, like H- and N-Ras, is dispensable for normal mouse development, at least
      in the presence of functional K-Ras 4B.

PMID- 14645536
TI  - Drosophila TGIF proteins are transcriptional activators.
AB  - The information carried by transforming growth factor beta (TGF-beta) signaling
      molecules induces profound responses in target cells. To restrict this
      information to appropriate cells, TGF-beta signaling pathways are tightly
      regulated by dynamic interactions with transcriptional activators and repressors.
      Numerous cross-species experiments have shown that TGF-beta family members and
      their signal transduction machinery (receptors and Smad signal transducers) are
      functionally conserved between vertebrates and invertebrates. TG-interacting
      factor (TGIF) is a homeodomain-containing transcriptional corepressor of TGF-beta
      dependent gene expression in mammals that is associated with holoprosencephaly in
      humans. Here we report a biochemical analysis of TGIF from zebra fish and
      Drosophila. Our study reveals an unprecedented role reversal between vertebrate
      and invertebrate TGIF proteins. Zebra fish TGIF, like its mammalian relative,
      interacts with general corepressors and represses TGF-beta-responsive gene
      expression. We identified a tandem duplication of TGIF genes in Drosophila. In
      contrast to vertebrate TGIFs, both Drosophila TGIFs strongly activate
      transcription. We also demonstrate that Drosophila TGIF proteins physically
      interact with both Mad and dSmad2, suggesting a role in Dpp and activin
      signaling. Thus, dTGIF may be the first transcription factor in the Drosophila
      activin pathway. Overall, our study suggests that assumptions about the
      functional equivalence of conserved proteins must be validated experimentally.

PMID- 14645537
TI  - Affinity purification of specific chromatin segments from chromosomal loci in
      yeast.
AB  - Single-copy gene and promoter regions have been excised from yeast chromosomes
      and have been purified as chromatin by conventional and affinity methods.
      Promoter regions isolated in transcriptionally repressed and activated states
      maintain their characteristic chromatin structures. Gel filtration analysis
      establishes the uniformity of the transcriptionally activated state. Activator
      proteins interact in the manner anticipated from previous studies in vivo. This
      work opens the way to the direct study of specific gene regions of eukaryotic
      chromosomes in diverse functional and structural states.

PMID- 14645538
TI  - Novel methyltransferase for modified uridine residues at the wobble position of
      tRNA.
AB  - We have identified a novel tRNA methyltransferase in Saccharomyces cerevisiae
      that we designate Trm9. This enzyme, the product of the YML014w gene, catalyzes
      the esterification of modified uridine nucleotides, resulting in the formation of
      5-methylcarbonylmethyluridine in tRNA(Arg3) and 5-methylcarbonylmethyl-2
      thiouridine in tRNA(Glu). In intact yeast cells, disruption of the TRM9 gene
      results in the complete loss of these modified wobble bases and increased
      sensitivity at 37 degrees C to paromomycin, a translational inhibitor. These
      results suggest a role for this potentially reversible methyl esterification
      reaction when cells are under stress.

PMID- 14645539
TI  - Regulation of protein tyrosine kinase signaling by substrate degradation during
      brain development.
AB  - Disabled-1 (Dab1) is a cytoplasmic adaptor protein that regulates neuronal
      migrations during mammalian brain development. Dab1 function in vivo depends on
      tyrosine phosphorylation, which is stimulated by extracellular Reelin and
      requires Src family kinases. Reelin signaling also negatively regulates Dab1
      protein levels in vivo, and reduced Dab1 levels may be part of the mechanism that
      regulates neuronal migration. We have made use of mouse embryo cortical neuron
      cultures in which Reelin induces Dab1 tyrosine phosphorylation and Src family
      kinase activation. We have found that Dab1 is normally stable, but in response to
      Reelin it becomes polyubiquitinated and degraded via the proteasome pathway. We
      have established that tyrosine phosphorylation of Dab1 is required for its
      degradation. Dab1 molecules lacking phosphotyrosine are not degraded in neurons
      in which the Dab1 degradation pathway is active. The requirements for Reelin
      induced degradation of Dab1 in vitro correctly predict Dab1 protein levels in
      vivo in different mutant mice. We also provide evidence that Dab1
      serine/threonine phosphorylation may be important for Dab1 tyrosine
      phosphorylation. Our data provide the first evidence for how Reelin down
      regulates Dab1 protein expression in vivo. Dab1 degradation may be important for
      ensuring a transient Reelin response and may play a role in normal brain
      development.

PMID- 14645541
TI  - Organization of mammalian cytoplasm.
AB  - Although the role of macromolecular interactions in cell function has attracted
      considerable attention, important questions about the organization of cells
      remain. To help clarify this situation, we used a simple protocol that measures
      macromolecule release after gentle permeabilization for the examination of the
      status of endogenous macromolecules. Treatment of Chinese hamster ovary cells
      with saponin under carefully controlled conditions allowed entry of molecules of
      at least 800 kDa; however, there were minimal effects on internal cellular
      architecture and protein synthesis remained at levels comparable to those seen
      with intact cells. Most importantly, total cellular protein and RNA were released
      from these cells extremely slowly. The release of actin-binding proteins and a
      variety of individual cytoplasmic proteins mirrored that of total protein, while
      marker proteins from subcellular compartments were not released. In contrast,
      glycolytic enzymes leaked rapidly, indicating that cells contain at least two
      distinct populations of cytoplasmic proteins. Addition of microfilament
      disrupting agents led to rapid and extensive release of cytoplasmic
      macromolecules and a dramatic reduction in protein synthesis. These observations
      support the conclusion that mammalian cells behave as highly organized,
      macromolecular assemblies (dependent on the actin cytoskeleton) in which
      endogenous macromolecules normally are not free to diffuse over large distances.

PMID- 14645540
TI  - DeltaRaf-1:ER* bypasses the cyclic AMP block of extracellular signal-regulated
      kinase 1 and 2 activation but not CDK2 activation or cell cycle reentry.
AB  - Elevation of cellular cyclic AMP (cAMP) levels inhibits cell cycle reentry in a
      variety of cell types. While cAMP can prevent the activation of Raf-1 and
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) by growth factors, we now
      show that activation of ERK1/2 by DeltaRaf-1:ER is insensitive to cAMP. Despite
      this, DeltaRaf-1:ER-stimulated DNA synthesis is still inhibited by cAMP,
      indicating a cAMP-sensitive step downstream of ERK1/2. Although cyclin D1
      expression has been proposed as an alternative target for cAMP, we found that
      cAMP could inhibit DeltaRaf-1:ER-induced cyclin D1 expression only in Rat-1
      cells, not in CCl39 or NIH 3T3 cells. DeltaRaf-1:ER-stimulated activation of CDK2
      was strongly inhibited by cAMP in all three cell lines, but cAMP had no effect on
      the induction of p21(CIP1). cAMP blocked the fetal bovine serum (FBS)-induced
      degradation of p27(KIP1); however, loss of p27(KIP1) in response to DeltaRaf-1:ER
      was less sensitive in CCl39 and Rat-1 cells and was completely independent of
      cAMP in NIH 3T3 cells. The most consistent effect of cAMP was to block both FBS-
      and DeltaRaf-1:ER-induced expression of Cdc25A and cyclin A, two important
      activators of CDK2. When CDK2 activity was bypassed by activation of the ER-E2F1
      fusion protein, cAMP no longer inhibited expression of Cdc25A or cyclin A but
      still inhibited DNA synthesis. These studies reveal multiple points of cAMP
      sensitivity during cell cycle reentry. Inhibition of Raf-1 and ERK1/2 activation
      may operate early in G(1), but when this early block is bypassed by DeltaRaf
      1:ER, cells still fail to enter S phase due to inhibition of CDK2 or targets
      downstream of E2F1.

PMID- 14645542
TI  - A stem structure in fibroblast growth factor receptor 2 transcripts mediates cell
      type-specific splicing by approximating intronic control elements.
AB  - Alternative splicing of fibroblast growth factor receptor 2 (FGFR2) occurs in a
      cell-type-specific manner with the mutually exclusive use of exon IIIb or exon
      IIIc. Specific inclusion of exon IIIb is observed in epithelial cells, whereas
      exon IIIc inclusion is seen in mesenchymal cells. Epithelium-specific activation
      of exon IIIb and repression of exon IIIc are coordinately regulated by intronic
      activating sequence 2 (IAS2) and intronic splicing activator and repressor (ISAR)
      elements in FGFR2 pre-mRNA. Previously, it has been suggested that IAS2 and a 20
      nucleotide core sequence of ISAR form a stem structure that allows for the proper
      regulation of FGFR2 alternative splicing. Replacement of IAS2 and the ISAR core
      with random sequences capable of stem formation resulted in the proper activation
      of exon IIIb and repression of exon IIIc in epithelial cells. Given the high
      degree of phylogenetic conservation of the IAS2-ISAR core structure and the fact
      that unrelated stem-forming sequences could functionally substitute for IAS2 and
      ISAR elements, we postulated that the stem structure facilitated the
      approximation of intronic control elements. Indeed, deletion of the entire stem
      loop region and juxtaposition of sequences immediately upstream of IAS2 with
      sequences immediately downstream of the ISAR core maintained proper cell-type
      specific inclusion of exon IIIb. These data demonstrate that IAS2 and the ISAR
      core are dispensable for the cell-type-specific activation of exon IIIb; thus,
      the major, if not the sole, role of the IAS2-ISAR stem in exon IIIb activation is
      to approximate sequences upstream of IAS2 with sequences downstream of the ISAR
      core. The downstream sequence is very likely a highly conserved GCAUG element,
      which we show was required for efficient exon IIIb activation.

PMID- 14645543
TI  - The c-myc insulator element and matrix attachment regions define the c-myc
      chromosomal domain.
AB  - Insulator elements and matrix attachment regions are essential for the
      organization of genetic information within the nucleus. By comparing the pattern
      of histone modifications at the mouse and human c-myc alleles, we identified an
      evolutionarily conserved boundary at which the c-myc transcription unit is
      separated from the flanking condensed chromatin enriched in lysine 9-methylated
      histone H3. This region harbors the c-myc insulator element (MINE), which
      contains at least two physically separable, functional activities: enhancer
      blocking activity and barrier activity. The enhancer-blocking activity is
      mediated by CTCF. Chromatin immunoprecipitation assays demonstrate that CTCF is
      constitutively bound at the insulator and at the promoter region independent of
      the transcriptional status of c-myc. This result supports an architectural role
      of CTCF rather than a regulatory role in transcription. An additional higher
      order nuclear organization of the c-myc locus is provided by matrix attachment
      regions (MARs) that define a domain larger than 160 kb. The MARs of the c-myc
      domain do not act to prevent the association of flanking regions with lysine 9
      methylated histones, suggesting that they do not function as barrier elements.

PMID- 14645544
TI  - Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in
      homeostasis, regeneration, and homing.
AB  - We have explored the functional implications of inducible alpha4 integrin
      deletion during adult hematopoiesis by generating a conditional-knockout mouse
      model, and we show that alpha4 integrin-deficient hematopoietic progenitor cells
      accumulate in the peripheral blood soon after interferon-induced gene deletion.
      Although their numbers gradually stabilize at a lower level, progenitor cell
      influx into the circulation continues at above-normal levels for more than 50
      weeks. Concomitantly, a progressive accumulation of progenitors occurs within the
      spleen. In addition, the regeneration of erythroid and myeloid progenitor cells
      is delayed during stress hematopoiesis induced by phenylhydrazine or by 5
      fluorouracil, suggesting impairment in early progenitor expansion in the absence
      of alpha4 integrin. Moreover, in transplantation studies, homing of alpha4(-/-)
      cells to the bone marrow, but not to the spleen, is selectively impaired, and
      short-term engraftment is critically delayed in the early weeks after
      transplantation. Thus, conditional deletion of alpha4 integrin in adult mice is
      accompanied by a novel hematopoietic phenotype during both homeostasis and
      recovery from stress, a phenotype that is distinct from the ones previously
      described in alpha4 integrin-null chimeras and beta1 integrin-conditional
      knockouts.

PMID- 14645546
TI  - Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha
      in hypoxic gene regulation.
AB  - Transcriptional responses to hypoxia are primarily mediated by hypoxia-inducible
      factor (HIF), a heterodimer of HIF-alpha and the aryl hydrocarbon receptor
      nuclear translocator subunits. The HIF-1alpha and HIF-2alpha subunits are
      structurally similar in their DNA binding and dimerization domains but differ in
      their transactivation domains, implying they may have unique target genes.
      Previous studies using Hif-1alpha(-/-) embryonic stem and mouse embryonic
      fibroblast cells show that loss of HIF-1alpha eliminates all oxygen-regulated
      transcriptional responses analyzed, suggesting that HIF-2alpha is dispensable for
      hypoxic gene regulation. In contrast, HIF-2alpha has been shown to regulate some
      hypoxia-inducible genes in transient transfection assays and during embryonic
      development in the lung and other tissues. To address this discrepancy, and to
      identify specific HIF-2alpha target genes, we used DNA microarray analysis to
      evaluate hypoxic gene induction in cells expressing HIF-2alpha but not HIF
      1alpha. In addition, we engineered HEK293 cells to express stabilized forms of
      HIF-1alpha or HIF-2alpha via a tetracycline-regulated promoter. In this first
      comparative study of HIF-1alpha and HIF-2alpha target genes, we demonstrate that
      HIF-2alpha does regulate a variety of broadly expressed hypoxia-inducible genes,
      suggesting that its function is not restricted, as initially thought, to
      endothelial cell-specific gene expression. Importantly, HIF-1alpha (and not HIF
      2alpha) stimulates glycolytic gene expression in both types of cells, clearly
      showing for the first time that HIF-1alpha and HIF-2alpha have unique targets.

PMID- 14645547
TI  - Growth suppression by acute promyelocytic leukemia-associated protein PLZF is
      mediated by repression of c-myc expression.
AB  - The transcriptional repressor PLZF was identified by its translocation with
      retinoic acid receptor alpha in t(11;17) acute promyelocytic leukemia (APL).
      Ectopic expression of PLZF leads to cell cycle arrest and growth suppression,
      while disruption of normal PLZF function is implicated in the development of APL.
      To clarify the function of PLZF in cell growth and survival, we used an inducible
      PLZF cell line in a microarray analysis to identify the target genes repressed by
      PLZF. One prominent gene identified was c-myc. The array analysis demonstrated
      that repression of c-myc by PLZF led to a reduction in c-myc-activated
      transcripts and an increase in c-myc-repressed transcripts. Regulation of c-myc
      by PLZF was shown to be both direct and reversible. An interaction between PLZF
      and the c-myc promoter could be detected both in vitro and in vivo. PLZF
      repressed the wild-type c-myc promoter in a reporter assay, dependent on the
      integrity of the binding site identified in vitro. PLZF binding in vivo was
      coincident with a decrease in RNA polymerase occupation of the c-myc promoter,
      indicating that repression occurred via a reduction in the initiation of
      transcription. Finally, expression of c-myc reversed the cell cycle arrest
      induced by PLZF. These data suggest that PLZF expression maintains a cell in a
      quiescent state by repressing c-myc expression and preventing cell cycle
      progression. Loss of this repression through the translocation that occurs in
      t(11;17) would have serious consequences for cell growth control.

PMID- 14645548
TI  - Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding
      domain binding site interactions with and inhibition of serine/threonine protein
      phosphatases PP1 and PP2A.
AB  - Previously it has been reported that caveolin-1 (cav-1) has antiapoptotic
      activities in prostate cancer cells and functions downstream of androgenic
      stimulation. In this study, we demonstrate that cav-1 overexpression
      significantly reduced thapsigargin (Tg)-stimulated apoptosis. Examination of the
      phosphatidylinositol 3-kinase (PI3-K)/Akt signaling cascade revealed higher
      activities of PDK1 and Akt but not PI3-K in cav-1-stimulated cells compared to
      control cells. We subsequently found that cav-1 interacts with and inhibits
      serine/threonine protein phosphatases PP1 and PP2A through scaffolding domain
      binding site interactions. Deletion of the cav-1 scaffolding domain significantly
      reduces phosphorylated Akt and cell viability compared with wild-type cav-1.
      Analysis of potential substrates for PP1 and PP2A revealed that cav-1-mediated
      inhibition of PP1 and PP2A leads to increased PDK1, Akt, and ERK1/2 activities.
      We demonstrate that increased Akt activities are largely responsible for cav-1
      mediated cell survival using dominant-negative Akt mutants and specific
      inhibitors to MEK1/MEK and show that cav-1 increases the half-life of
      phosphorylated PDK1 and Akt after inhibition of PI3-K by LY294002. We further
      demonstrate that cav-1-stimulated Akt activities lead to increased
      phosphorylation of multiple Akt substrates, including GSK3, FKHR, and MDM2. In
      addition, overexpression of cav-1 significantly increases translocation of
      phosphorylated androgen receptor to nucleus. Our studies therefore reveal a novel
      mechanism of Akt activation in prostate cancer and potentially other
      malignancies.

PMID- 14645549
TI  - Targeting of adenovirus via genetic modification of the viral capsid combined
      with a protein bridge.
AB  - A potential barrier to the development of genetically targeted adenovirus (Ad)
      vectors for cell-specific delivery of gene therapeutics lies in the fact that
      several types of targeting protein ligands require posttranslational
      modifications, such as the formation of disulfide bonds, which are not available
      to Ad capsid proteins due to their nuclear localization during assembly of the
      virion. To overcome this problem, we developed a new targeting strategy, which
      combines genetic modifications of the Ad capsid with a protein bridge approach,
      resulting in a vector-ligand targeting complex. The components of the complex
      associate by virtue of genetic modifications to both the Ad capsid and the
      targeting ligand. One component of this mechanism of association, the Fc-binding
      domain of Staphylococcus aureus protein A, is genetically incorporated into the
      Ad fiber protein. The ligand is comprised of a targeting component fused with the
      Fc domain of immunoglobulin, which serves as a docking moiety to bind to these
      genetically modified fibers during the formation of the Ad-ligand complex. The
      modular design of the ligand solves the problem of structural and biosynthetic
      compatibility with the Ad and thus facilitates targeting of the vector to a
      variety of cellular receptors. Our study shows that targeting ligands
      incorporating the Fc domain and either an anti-CD40 single-chain antibody or
      CD40L form stable complexes with protein A-modified Ad vectors, resulting in
      significant augmentation of gene delivery to CD40-positive target cells. Since
      this gene transfer is independent of the expression of the native Ad5 receptor by
      the target cells, this strategy results in the derivation of truly targeted Ad
      vectors suitable for tissue-specific gene therapy.

PMID- 14645550
TI  - Antibody prophylaxis and therapy against West Nile virus infection in wild-type
      and immunodeficient mice.
AB  - West Nile virus (WNV) is a mosquito-borne Flavivirus that causes encephalitis in
      a subset of susceptible humans. Current treatment for WNV infections is
      supportive, and no specific therapy or vaccine is available. In this study, we
      directly tested the prophylactic and therapeutic efficacy of polyclonal
      antibodies against WNV. Passive administration of human gamma globulin or mouse
      serum prior to WNV infection protected congenic wild-type, B-cell-deficient (
      micro MT), and T- and B-cell-deficient (RAG1) C57BL/6J mice. Notably, no
      increased mortality due to immune enhancement was observed. Although immune
      antibody completely prevented morbidity and mortality in wild-type mice, its
      effect was not durable in immunocompromised mice: many micro MT and RAG1 mice
      eventually succumbed to infection. Thus, antibody by itself did not completely
      eliminate viral reservoirs in host tissues, consistent with an intact cellular
      immune response being required for viral clearance. In therapeutic postexposure
      studies, human gamma globulin partially protected against WNV-induced mortality.
      In micro MT mice, therapy had to be initiated within 2 days of infection to gain
      a survival benefit, whereas in the wild-type mice, therapy even 5 days after
      infection reduced mortality. This time point is significant because between days
      4 and 5, WNV was detected in the brains of infected mice. Thus, passive transfer
      of immune antibody improves clinical outcome even after WNV has disseminated into
      the central nervous system.

PMID- 14645551
TI  - Stability and morphology comparisons of self-assembled virus-like particles from
      wild-type and mutant human hepatitis B virus capsid proteins.
AB  - Instead of displaying the wild-type selective export of virions containing mature
      genomes, human hepatitis B virus (HBV) mutant I97L, changing from an isoleucine
      to a leucine at amino acid 97 of HBV core antigen (HBcAg), lost the high
      stringency of selectivity in genome maturity during virion export. To understand
      the structural basis of this so-called "immature secretion" phenomenon, we
      compared the stability and morphology of self-assembled capsid particles from the
      wild-type and mutant I97L HBV, in either full-length (HBcAg1-183) or truncated
      core protein contexts (HBcAg1-149 and HBcAg1-140). Using negative staining and
      electron microscopy, full-length particles appear as "thick-walled" spherical
      particles with little interior space, whereas truncated particles appear as "thin
      walled" spherical particles with a much larger inner space. We found no
      significant differences in capsid stability between wild-type and mutant I97L
      particles under denaturing pH and temperature in either full-length or truncated
      core protein contexts. In general, HBV capsid particles (HBcAg1-183, HBcAg1-149,
      and HBcAg1-140) are very robust but will dissociate at pH 2 or 14, at
      temperatures higher than 75 degrees C, or in 0.1% sodium dodecyl sulfate (SDS).
      An unexpected upshift banding pattern of the SDS-treated full-length particles
      during agarose gel electrophoresis is most likely caused by disulfide bonding of
      the last cysteine of HBcAg. HBV capsids are known to exist in natural infection
      as dimorphic T=3 or T=4 icosahedral particles. No difference in the ratio between
      T=3 (78%) and T=4 particles (20.3%) are found between wild-type HBV and mutant
      I97L in the context of HBcAg1-140. In addition, we found no difference in capsid
      stability between T=3 and T=4 particles successfully separated by using a novel
      agarose gel electrophoresis procedure.

PMID- 14645552
TI  - Further evidence that papillomavirus capsids exist in two distinct conformations.
AB  - Cell surface heparan sulfate proteoglycans (HSPGs) serve as primary attachment
      receptors for human papillomaviruses (HPVs). To demonstrate that a biologically
      functional HPV-receptor interaction is restricted to a specific subset of HSPGs,
      we first explored the role of HSPG glucosaminoglycan side chain modifications. We
      demonstrate that HSPG O sulfation is essential for HPV binding and infection,
      whereas de-N-sulfated heparin interfered with VLP binding but not with HPV
      pseudoinfection. This points to differences in VLP-HSPG and pseudovirion-HSPG
      interactions. Interestingly, internalization kinetics of VLPs and pseudovirions,
      as measured by fluorescence-activated cell sorting analysis, also differ
      significantly with approximate half times of 3.5 and 7.5 h, respectively. These
      data suggest that differences in HSPG binding significantly influence postbinding
      events. We also present evidence that pseudovirions undergo a conformational
      change after cell attachment. A monoclonal antibody (H33.J3), which displays
      negligible effectiveness in preattachment neutralization assays, efficiently
      neutralizes cell-bound virions. However, no difference in H33.J3 binding to
      pseudovirions and VLPs was observed in enzyme-linked immunosorbent assay and
      virus capture assays. In contrast to antibody H33.B6, which displays equal
      efficiencies in pre- and postattachment neutralization assays, H33.J3 does not
      block VLP binding to heparin, demonstrating that it interferes with steps
      subsequent to virus binding. Our data strongly suggest that H33.J3 recognizes a
      conformation-dependent epitope in capsid protein L1, which undergoes a structural
      change after cell attachment.

PMID- 14645553
TI  - Role of the cytoplasmic domain of the Newcastle disease virus fusion protein in
      association with lipid rafts.
AB  - To explore the association of the Newcastle disease virus (NDV) fusion (F)
      protein with cholesterol-rich membrane domains, its localization in detergent
      resistant membranes (DRMs) in transfected cells was characterized. After
      solubilization of cells expressing the F protein with 1% Triton X-100 at 4
      degrees C, ca. 40% of total, cell-associated F protein fractionated with
      classical DRMs with densities of 1.07 to l.14 as defined by flotation into
      sucrose density gradients. Association of the F protein with this cell fraction
      was unaffected by the cleavage of F(0) to F(1) and F(2) or by coexpression of the
      NDV attachment protein, the hemagglutinin-neuraminidase protein (HN).
      Furthermore, elimination by mutation, of potential palmitate addition sites in
      and near the F-protein transmembrane domain had no effect on F-protein
      association with DRMs. Rather, specific deletions of the cytoplasmic domain of
      the F protein eliminated association with classical DRMs. Comparisons of
      deletions that affected fusion activity of the protein and deletions that
      affected DRM association suggested that there is no direct link between the cell
      cell fusion activity of the F protein and DRM association. Furthermore, depletion
      of cholesterol from cells expressing F and HN protein, while eliminating DRM
      association, had no effect on the ability of these cells to fuse with avian red
      blood cells. These results suggest that specific localization of the F protein in
      cholesterol-rich membrane domains is not required for cell-to-cell fusion.
      Paramyxovirus F-protein cytoplasmic domains have been implicated in virus
      assembly. The results presented here raise the possibility that the cytoplasmic
      domain is important in virus assembly at least in part because it directs the
      protein to cholesterol-rich membrane domains.

PMID- 14645554
TI  - Varied immunity generated in mice by DNA vaccines with large and small hepatitis
      delta antigens.
AB  - Whether the hepatitis delta virus (HDV) DNA vaccine can induce anti-HDV
      antibodies has been debatable. The role of the isoprenylated motif of hepatitis
      delta antigens (HDAg) in the generation of immune responses following DNA-based
      immunization has never been studied. Plasmids p2577L, encoding large HDAg (L
      HDAg), p2577S, expressing small HDAg (S-HDAg), and p25L-211S, encoding a mutant
      form of L-HDAg with a cysteine-to-serine mutation at codon 211, were constructed
      in this study. Mice were intramuscularly injected with the plasmids. The anti-HDV
      antibody titers, T-cell proliferation responses, T-helper responses, and HDV
      specific, gamma interferon (IFN-gamma)-producing CD8(+) T cells were analyzed.
      Animals immunized with p2577S showed a strong anti-HDV antibody response.
      Conversely, only a low titer of anti-HDV antibodies was detected in mice
      immunized with p2577L. Epitope mapping revealed that the anti-HDV antibodies
      generated by p2577L vaccination hardly reacted with epitope amino acids 174 to
      194, located at the C terminus of S-HDAg. All of the HDAg-encoding plasmids could
      induce significant T-cell proliferation responses and generate Th1 responses and
      HDV-specific, IFN-gamma-producing CD8(+) T cells. In conclusion, HDAg-specific
      antibodies definitely exist following DNA vaccination. The magnitudes of the
      humoral immune responses generated by L-HDAg- and S-HDAg-encoding DNA vaccines
      are different. The isoprenylated motif can mask epitope amino acids 174 to 195 of
      HDAg but does not interfere with cellular immunity following DNA-based
      immunization. These findings are important for the choice of a candidate HDV DNA
      vaccine in the future.

PMID- 14645555
TI  - Effects of a single amino acid substitution within the p2 region of human
      immunodeficiency virus type 1 on packaging of spliced viral RNA.
AB  - Human immunodeficiency virus type 1 encapsidates two copies of viral genomic RNA
      in the form of a dimer. The dimerization process initiates via a 6-nucleotide
      palindrome that constitutes the loop of a viral RNA stem-loop structure (i.e.,
      stem loop 1 [SL1], also termed the dimerization initiation site [DIS]) located
      within the 5' untranslated region of the viral genome. We have now shown that
      deletion of the entire DIS sequence virtually eliminated viral replication but
      that this impairment was overcome by four second-site mutations located within
      the matrix (MA), capsid (CA), p2, and nucleocapsid (NC) regions of Gag.
      Interestingly, defective viral RNA dimerization caused by the DeltaDIS deletion
      was not significantly corrected by these compensatory mutations, which did,
      however, allow the mutated viruses to package wild-type levels of this DIS
      deleted viral RNA while excluding spliced viral RNA from encapsidation. Further
      studies demonstrated that the compensatory mutation T12I located within p2,
      termed MP2, sufficed to prevent spliced viral RNA from being packaged into the
      DeltaDIS virus. Consistently, the DeltaDIS-MP2 virus displayed significantly
      higher levels of infectiousness than did the DeltaDIS virus. The importance of
      position T12 in p2 was further demonstrated by the identification of four point
      mutations,T12D, T12E, T12G, and T12P, that resulted in encapsidation of spliced
      viral RNA at significant levels. Taken together, our data demonstrate that
      selective packaging of viral genomic RNA is influenced by the MP2 mutation and
      that this represents a major mechanism for rescue of viruses containing the
      DeltaDIS deletion.

PMID- 14645556
TI  - Intra- and intermolecular disulfide bonds of the GP2b glycoprotein of equine
      arteritis virus: relevance for virus assembly and infectivity.
AB  - Equine arteritis virus (EAV) is an enveloped, positive-strand RNA virus belonging
      to the family Arteriviridae of the order NIDOVIRALES: EAV virions contain six
      different envelope proteins. The glycoprotein GP(5) (previously named G(L)) and
      the unglycosylated membrane protein M are the major envelope proteins, while the
      glycoproteins GP(2b) (previously named G(S)), GP(3), and GP(4) are minor
      structural proteins. The unglycosylated small hydrophobic envelope protein E is
      present in virus particles in intermediate molar amounts compared to the other
      transmembrane proteins. The GP(5) and M proteins are both essential for particle
      assembly. They occur as covalently linked heterodimers that constitute the basic
      protein matrix of the envelope. The GP(2b), GP(3), and GP(4) proteins occur as a
      heterotrimeric complex in which disulfide bonds play an important role. The
      function of this complex has not been established yet, but the available data
      suggest it to be involved in the viral entry process. Here we investigated the
      role of the four cysteine residues of the mature GP(2b) protein in the assembly
      of the GP(2b)/GP(3)/GP(4) complex. Open reading frames encoding cysteine-to
      serine mutants of the GP(2b) protein were expressed independently or from a full
      length infectious EAV cDNA clone. The results of these experiments support a
      model in which the cysteine residue at position 102 of GP(2b) forms an
      intermolecular cystine bridge with one of the cysteines of the GP(4) protein,
      while the cysteine residues at positions 48 and 137 of GP(2b) are linked by an
      intrachain disulfide bond. In this model, another cysteine residue in the GP(4)
      protein is responsible for the covalent association of GP(3) with the disulfide
      linked GP(2b)/GP(4) heterodimer. In addition, our data highlight the importance
      of the correct association of the minor EAV envelope glycoproteins for their
      efficient incorporation into viral particles and for virus infectivity.

PMID- 14645557
TI  - Changes in small intestinal homeostasis, morphology, and gene expression during
      rotavirus infection of infant mice.
AB  - Rotavirus is the most important cause of infantile gastroenteritis. Since in vivo
      mucosal responses to a rotavirus infection thus far have not been extensively
      studied, we related viral replication in the murine small intestine to
      alterations in mucosal structure, epithelial cell homeostasis, cellular kinetics,
      and differentiation. Seven-day-old suckling BALB/c mice were inoculated with 2 x
      10(4) focus-forming units of murine rotavirus and were compared to mock-infected
      controls. Diarrheal illness and viral shedding were recorded, and small
      intestinal tissue was evaluated for rotavirus (NSP4 and structural proteins)- and
      enterocyte-specific (lactase, SGLT1, and L-FABP) mRNA and protein expression.
      Morphology, apoptosis, proliferation, and migration were evaluated
      (immuno)histochemically. Diarrhea was observed from days 1 to 5 postinfection,
      and viral shedding was observed from days 1 to 10. Two peaks of rotavirus
      replication were observed at 1 and 4 days postinfection. Histological changes
      were characterized by the accumulation of vacuolated enterocytes. Strikingly, the
      number of vacuolated cells exceeded the number of cells in which viral
      replication was detectable. Apoptosis and proliferation were increased from days
      1 to 7, resulting in villous atrophy. Epithelial cell turnover was significantly
      higher (<4 days) than that observed in controls (7 days). Since epithelial
      renewal occurred within 4 days, the second peak of viral replication was most
      likely caused by infection of newly synthesized cells. Expression of enterocyte
      specific genes was downregulated in infected cells at mRNA and protein levels
      starting as early as 6 h after infection. In conclusion, we show for the first
      time that rotavirus infection induces apoptosis in vivo, an increase in
      epithelial cell turnover, and a shutoff of gene expression in enterocytes showing
      viral replication. The shutoff of enterocyte-specific gene expression, together
      with the loss of mature enterocytes through apoptosis and the replacement of
      these cells by less differentiated dividing cells, likely leads to a defective
      absorptive function of the intestinal epithelium, which contributes to rotavirus
      pathogenesis.

PMID- 14645558
TI  - Role of nonstructural proteins 3A and 3B in host range and pathogenicity of foot
      and-mouth disease virus.
AB  - The genome of foot-and-mouth disease virus (FMDV) differs from that of other
      picornaviruses in that it encodes a larger 3A protein (>50% longer than
      poliovirus 3A), as well as three copies of protein 3B (also known as VPg).
      Previous studies have shown that a deletion of amino acids 93 to 102 of the 153
      codon 3A protein is associated with an inability of a Taiwanese strain of FMDV
      (O/TAW/97) to cause disease in bovines. Recently, an Asian virus with a second 3A
      deletion (amino acids 133 to 143) has also been detected (N. J. Knowles et al.,
      J. Virol. 75:1551-1556, 2001). Genetically engineered viruses harboring the amino
      acids 93 to 102 or 133 to 143 grew well in porcine cells but replicated poorly in
      bovine cells, whereas a genetically engineered derivative of the O/TAW/97 virus
      expressing a full-length 3A (strain A12) grew well in both cell types.
      Interestingly, a virus with a deletion spanning amino acid 93 to 144 also grew
      well in porcine cells and caused disease in swine. Further, genetically
      engineered viruses containing only a single copy of VPg were readily recovered
      with the full-length 3A, the deleted 3A (amino acids 93 to 102), or the "super"
      deleted forms of 3A (missing amino acids 93 to 144). All of the single-VPg
      viruses were attenuated in porcine cells and replicated poorly in bovine cells.
      The single-VPg viruses produced a mild disease in swine, indicating that the VPg
      copy number is an important determinant of host range and virulence. The
      association of VPg copy number with increased virulence in vivo may help to
      explain why all naturally occurring FMDVs have retained three copies of VPg.

PMID- 14645559
TI  - The central region of human T-cell leukemia virus type 1 Tax protein contains
      distinct domains involved in subunit dimerization.
AB  - The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) can form
      homodimers. Tax dimerization contributes to optimal Tax activity involved in
      transactivation of the HTLV-1 promoter. The mechanisms used to form specific Tax
      dimers are poorly understood because the domains that mediate such interactions
      have not been clearly characterized. Here we have used different approaches (the
      two-hybrid assay in yeast, the glutathione S-transferase pull-down assay, and the
      Spot method) to study Tax-Tax interactions. Our results indicate that the
      integrity of the sequence of Tax, except for the last 16 amino acids (residues
      338 to 353), is critical, suggesting that Tax dimerization is dictated more by
      secondary structure than by primary structure. We were, however, able to delimit
      a central region involved in Tax self-association that encompasses the residues
      127 to 228. This region can be divided into three subdomains of dimerization: DD1
      (residues 127 to 146), DD2 (residues 181 to 194), and DD3 (residues 213 to 228).
      Moreover, the Tax mutants M22 (T130A and L131S) and M29 (K189A and R190S), with
      amino acid substitutions located in DD1 and DD2, respectively, were found to be
      impaired in Tax self-association.

PMID- 14645560
TI  - Comparison of the structures of three circoviruses: chicken anemia virus, porcine
      circovirus type 2, and beak and feather disease virus.
AB  - Circoviruses are small, nonenveloped icosahedral animal viruses characterized by
      circular single-stranded DNA genomes. Their genomes are the smallest possessed by
      animal viruses. Infections with circoviruses, which can lead to economically
      important diseases, frequently result in virus-induced damage to lymphoid tissue
      and immunosuppression. Within the family Circoviridae, different genera are
      distinguished by differences in genomic organization. Thus, Chicken anemia virus
      is in the genus Gyrovirus, while porcine circoviruses and Beak and feather
      disease virus belong to the genus CIRCOVIRUS: Little is known about the
      structures of circoviruses. Accordingly, we investigated the structures of these
      three viruses with a view to determining whether they are related. Three
      dimensional maps computed from electron micrographs showed that all three viruses
      have a T=1 organization with capsids formed from 60 subunits. Porcine circovirus
      type 2 and beak and feather disease virus show similar capsid structures with
      flat pentameric morphological units, whereas chicken anemia virus has stikingly
      different protruding pentagonal trumpet-shaped units. It thus appears that the
      structures of viruses in the same genus are related but that those of viruses in
      different genera are unrelated.

PMID- 14645561
TI  - Macrophage-tropic simian/human immunodeficiency virus chimeras use CXCR4, not
      CCR5, for infections of rhesus macaque peripheral blood mononuclear cells and
      alveolar macrophages.
AB  - After the nearly complete and irreversible depletion of CD4(+) T lymphocytes
      induced by highly pathogenic simian/human immunodeficiency virus chimeric viruses
      (SHIVs) during infections of rhesus monkeys, tissue macrophages are able to
      sustain high levels (>10(6) viral RNA copies/ml) of plasma viremia for several
      months. We recently reported that the virus present in the plasma during the late
      macrophage phase of infection had acquired changes that specifically targeted the
      V2 region of gp120 (H. Imamichi et al., Proc. Natl. Acad. Sci. USA 99:13813
      13818, 2002); some of these SHIV variants were macrophage-tropic (M-tropic).
      Those findings have been extended by examining the tropic properties, coreceptor
      usage, and gp120 structure of five independent SHIVs recovered directly from
      lymph nodes of late-stage animals. All of these tissue-derived SHIV isolates were
      able to infect alveolar macrophages. These M-tropic SHIVs used CXCR4, not CCR5,
      for infections of rhesus monkey PBMC and primary alveolar macrophages. Because
      the starting highly pathogenic T-tropic SHIV inoculum also utilized CXCR4, these
      results indicate that the acquisition of M-tropism in the SHIV-macaque system is
      not accompanied by a change in coreceptor usage. Compared to the initial T-tropic
      SHIV inoculum, tissue-derived M-tropic SHIVs from individual infected animals
      carry gp120s containing similar changes (specific amino acid deletions,
      substitutions, and loss of N-linked glycosylation sites), primarily within the V1
      and/or V2 regions of gp120.

PMID- 14645562
TI  - High-frequency homologous recombination between baculoviruses involves DNA
      replication.
AB  - We determined the frequency of DNA recombination between Bombyx mori
      nucleopolyhedroviruses (BmNPVs) and between BmNPV and the closely related
      Autographa californica NPV (AcMNPV) in BmN cells, Sf-21 cells, and larvae of
      Heliothis virescens. The BmN cells were coinfected with two BmNPVs, one with a
      mutation at the polyhedrin gene (polh) locus and a second carrying a lacZ gene
      marker cassette. Eleven different BmNPV mutants carrying the lacZ gene marker at
      various distances (1.4 to 61.7 kb) from polh were used for the coinfections. The
      Sf-21 cells and larvae of H. virescens were coinfected with wild-type AcMNPV and
      1 of the 11 lacZ-marked BmNPV mutants. In BmN cells, high-frequency recombination
      was detected as early as 15 h postcoinfection but not at 12 h postcoinfection. At
      18 h postcoinfection, the mean frequency of recombination ranged between 20.0 and
      35.4% when the polh and lacZ marker genes were separated by at least 9.7 kb. When
      these marker genes were separated by only 1.4 kb, the mean frequency of
      recombination was 2.7%. In BmN cells, the mean recombination frequency between
      two BmNPVs increased only marginally when the multiplicity of infection of each
      virus was increased 10-fold. In Sf-21 cells and the larvae of H. virescens, the
      recombination frequency between BmNPV and AcMNPV was </=1.0%. AcMNPV DNA
      replication occurred normally after the coinfection of Sf-21 cells. BmNPV DNA
      replication, however, was not detected, indicating that normal DNA replication by
      both viruses is required for high-frequency recombination.

PMID- 14645563
TI  - Reduction of natural adenovirus tropism to mouse liver by fiber-shaft exchange in
      combination with both CAR- and alphav integrin-binding ablation.
AB  - The primary receptor, the coxsackievirus and adenovirus receptor (CAR), and the
      secondary receptor, alphav integrins, are the tropism determinants of adenovirus
      (Ad) type 5. Inhibition of the interaction of both the fiber with CAR and the
      penton base with the alphav integrin appears to be crucial to the development of
      targeted Ad vectors, which specifically transduce a given cell population. In
      this study, we developed Ad vectors with ablation of both CAR and alphav integrin
      binding by mutating the fiber knob and the RGD motif of the penton base. We also
      replaced the fiber shaft domain with that derived from Ad type 35. High
      transduction efficiency in the mouse liver was suppressed approximately 130- to
      270-fold by intravenous administration of the double-mutant Ad vectors, which
      mutated two domains each of the fiber knob and shaft and the RGD motif of the
      penton base compared with those of conventional Ad vectors (type 5). Most
      significantly, the triple-mutant Ad vector containing the fiber knob with
      ablation of CAR binding ability, the fiber shaft of Ad type 35, and the penton
      base with a deletion of the RGD motif mediated a >30,000-fold lower level of
      mouse liver transduction than the conventional Ad vectors. This triple-mutant Ad
      vector also mediated reduced transduction in other organs (the spleen, kidney,
      heart, and lung). Viral DNA analysis showed that systemically delivered triple
      mutant Ad vector was primarily taken up by liver nonparenchymal cells and that
      most viral DNAs were easily degraded, resulting in little gene expression in the
      liver. These results suggest that the fiber knob, fiber shaft, and RGD motif of
      the penton base each plays an important role in Ad vector-mediated transduction
      to the mouse liver and that the triple-mutant Ad vector exhibits little tropism
      to any organs and appears to be a fundamental vector for targeted Ad vectors.

PMID- 14645564
TI  - Reduced cell turnover in bovine leukemia virus-infected, persistently
      lymphocytotic cattle.
AB  - Although nucleotide analogs like bromodeoxyuridine have been extensively used to
      estimate cell proliferation in vivo, precise dynamic parameters are scarce
      essentially because of the lack of adequate mathematical models. Besides recent
      developments on T cell dynamics, the turnover rates of B lymphocytes are largely
      unknown particularly in the context of a virally induced pathological disorder.
      Here, we aim to resolve this issue by determining the rates of cell proliferation
      and death during the chronic stage of the bovine leukemia virus (BLV) infection,
      called bovine persistent lymphocytosis (PL). Our methodology is based on direct
      intravenous injection of bromodeoxyuridine in association with subsequent flow
      cytometry. By this in vivo approach, we show that the death rate of PL B
      lymphocytes is significantly reduced (average death rate, 0.057 day(-1) versus
      0.156 day(-1) in the asymptomatic controls). Concomitantly, proliferation of the
      PL cells is also significantly restricted compared to the controls (average
      proliferation rate, 0.0046 day(-1) versus 0.0085 day(-1)). We conclude that
      bovine PL is characterized by a decreased cell turnover resulting both from a
      reduction of cell death and an overall impairment of proliferation. The cell
      dynamic parameters differ from those measured in sheep, an experimental model for
      BLV infection. Finally, cells expressing p24 major capsid protein ex vivo were
      not BrdU positive, suggesting an immune selection against proliferating virus
      positive lymphocytes. Based on a comparative leukemia approach, these
      observations might help to understand cell dynamics during other
      lymphoproliferative disease such as chronic lymphocytic leukemia or human T-cell
      lymphotropic virus-induced adult T-cell leukemia in humans.

PMID- 14645565
TI  - Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is a host
      component of human immunodeficiency virus type 1 virions.
AB  - Barrier-to-autointegration factor (BAF) is a conserved human chromatin protein
      exploited by retroviruses. Previous investigators showed that BAF binds double
      stranded DNA nonspecifically and is a host component of preintegration complexes
      (PICs) isolated from cells infected with human immunodeficiency virus type 1 (HIV
      1) or Moloney murine leukemia virus. BAF protects PIC structure and stimulates
      the integration of salt-stripped PICs into target DNA in vitro. PICs are thought
      to acquire BAF from the cytoplasm during infection. However, we identified two
      human tissues (of 16 tested) in which BAF mRNA was not detected: thymus and
      peripheral blood leukocytes, which are enriched in CD4(+) T lymphocytes and
      macrophage precursors, respectively. BAF protein was detected in activated but
      not resting CD4(+) T lymphocytes; thus, if BAF were essential for PIC function,
      we hypothesized that virions might "bring their own BAF." Supporting this model,
      BAF copurified with HIV-1 virions that were digested with subtilisin to remove
      microvesicle contaminants, and BAF was present in approximately zero to three
      copies per virion. In three independent assays, BAF bound directly to both p55
      Gag (the structural precursor of HIV-1 virions) and its cleaved product, matrix.
      Using lysates from cells overexpressing Gag, endogenous BAF and Gag were
      coimmunoprecipitated by antibodies against Gag. Purified recombinant BAF had low
      micromolar affinities (1.1 to 1.4 micro M) for recombinant Gag and matrix. We
      conclude that BAF is present at low levels in incoming virions, in addition to
      being acquired from the cytoplasm of newly infected cells. We further conclude
      that BAF might contribute to the assembly or activity of HIV-1 PICs through
      direct binding to matrix, as well as DNA.

PMID- 14645566
TI  - An internal ribosome entry site directs translation of the murine
      gammaherpesvirus 68 MK3 open reading frame.
AB  - The gammaherpesviruses characteristically drive the proliferation of latently
      infected lymphocytes. The murine gammaherpesvirus 68 (MHV-68) MK3 protein
      contributes to this process in vivo by evading CD8(+)-T-cell recognition during
      latency, as well as during lytic infection. We analyzed some of the molecular
      mechanisms that control MK3 expression. No dedicated MK3 mRNA was detected.
      Instead, the MK3 open reading frame (ORF) was transcribed as part of a
      bicistronic mRNA, downstream of a previously unidentified ORF, 13M. The 13M/MK3
      promoter appeared to extend approximately 1 kb 5' of the transcription start site
      and included elements both dependent on and independent of the ORF50 lytic
      transactivator. MK3 was translated from the bicistronic transcript by virtue of
      an internal ribosome entry site (IRES) element. RNA structure mapping identified
      two stem-loops between 13M and MK3 that were sufficient for IRES activity in a
      bicistronic reporter plasmid and a third stem-loop just within the MK3 coding
      sequence, with a subtler, perhaps regulatory role. Overall, translation of the
      MHV-68 MK3 bore a striking resemblance to that of the Kaposi's sarcoma-associated
      herpesvirus vFLIP, suggesting that IRES elements are a common theme of latent
      gammaherpesvirus immune evasion in proliferating cells.

PMID- 14645567
TI  - Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus.
AB  - Alphavirus nsP3 phosphoprotein is essential for virus replication and functions
      initially within polyprotein P123 or P23 components of the short-lived minus
      strand replicase, and upon polyprotein cleavage, mature nsP3 likely functions
      also in plus-strand synthesis. We report the identification of a second nsP3
      mutant from among the A complementation group of Sindbis virus (SIN) heat
      resistant strain, ts RNA-negative mutants. The ts138 mutant possessed a change of
      G4303 to C, predicting an Ala68-to-Gly alteration that altered a conserved His
      Ala-Val tripeptide in the ancient (pre-eukaryotic), "X" or histone 2A
      phosphoesterase-like macrodomain that in SIN encompasses nsP3 residues 1 to 161
      and whose role is unknown. We undertook comparative analysis of three nsP3 N
      terminal region mutants and observed (i) that nsP3 and nsP2 functioned initially
      as a single unit as deduced from complementation analysis and in agreement with
      our previous studies, (ii) that the degree of phosphorylation varied among the
      nsP3 mutants, and (iii) that reduced phosphorylation of nsP3 correlated with
      reduced minus-strand synthesis. The most striking phenotype was exhibited by ts4
      (Ala268 to Val), which after shift to 40 degrees C made significantly
      underphosphorylated P23/nsP3 and lost selectively the ability to make minus
      strands. After shift to 40 degrees C, mutant ts7 (Phe312 to Ser) made
      phosphorylated P23/nsP3 and minus strands but failed to increase plus-strand
      synthesis. Macrodomain mutant ts138 was intermediate, making at 40 degrees C
      partially phosphorylated P23/nsP3 and reduced amounts of minus strands. The
      mutants were able to assemble their nsPs at 40 degrees C into complexes that were
      membrane associated. Our analyses argue that P23/P123 phosphorylation is affected
      by macrodomain and Ala268 region sequences and in turn affects the efficient
      transcription of the alphavirus genome.

PMID- 14645568
TI  - Evolution of human calicivirus RNA in vivo: accumulation of mutations in the
      protruding P2 domain of the capsid leads to structural changes and possibly a new
      phenotype.
AB  - In the present study we report on evolution of calicivirus RNA from a patient
      with chronic diarrhea (i.e., lasting >2 years) and viral shedding. Partial
      sequencing of open reading frame 1 (ORF1) from 12 consecutive isolates revealed
      shedding of a genogroup II virus with relatively few nucleotide changes during a
      1-year period. The entire capsid gene (ORF2) was also sequenced from the same
      isolates and found to contain 1,647 nucleotides encoding a protein of 548 amino
      acids with similarities to the Arg320 and Mx strains. Comparative sequence
      analysis of ORF2 revealed 32 amino acid changes during the year. It was notable
      that the vast majority of the cumulative amino acid changes (8 of 11) appeared
      within residues 279 to 405 located within the hypervariable domain (P2) of the
      capsid protein and hence were subject to immune pressure. An interesting and
      novel observation was that the accumulated amino acid changes in the P2 domain
      resulted in predicted structural changes, including disappearance of a helix
      structure, and thus a possible emergence of a new phenotype. FUT2 gene
      polymorphism characterization revealed that the patient is heterozygous at
      nucleotide 428 and thus Secretor(+), a finding in accordance with the hypothesis
      of FUT2 gene polymorphism and calicivirus susceptibility. To our knowledge, this
      is the first report of RNA evolution of calicivirus in a single individual, and
      our data suggest an immunity-driven mechanism for viral evolution. We also report
      on chronic virus excretion, immunoglobulin treatment, and modification of
      clinical symptoms; our observations from these studies, together with the FUT2
      gene characterization, may lead to a better understanding of calicivirus
      pathogenesis.

PMID- 14645569
TI  - Different heparan sulfate proteoglycans serve as cellular receptors for human
      papillomaviruses.
AB  - Papillomaviruses replicate in stratified epithelia of skin and mucosa. Infection
      with certain human papillomavirus (HPV) types is the main cause of anogenital
      neoplasia, in particular cervical cancer. Early events of papillomavirus
      infectivity are poorly understood. While heparan sulfate proteoglycans (HSPGs)
      mediate initial binding to the cell surface, the class of proteins carrying
      heparan sulfates has not been defined. Here we examined two processes of
      papillomavirus infection, attachment of virus-like particles (VLP) to cells and
      infection with authentic HPV type 11 (HPV11) virions. Of the HSPGs, syndecan-1 is
      the major epithelial form and is strongly upregulated in wound edge
      keratinocytes. We employed K562 cells, which lack HSPGs except minor amounts of
      endogenous betaglycan, and stable clones that express cDNAs of syndecan-1,
      syndecan-4, or glypican-1. Binding of VLP correlated with levels of heparan
      sulfate on the cell surface. Parental K562 bound HPV16 VLP weakly, whereas all
      three K562 transfectants demonstrated enhanced binding, with the highest binding
      capacity observed for syndecan-1-transfected cells, which also expressed the most
      HSPG. For HPV11 infectivity assays, a high virion inoculum was required to infect
      K562 cells, whereas ectopic expression of syndecan-1 increased permissiveness
      eightfold and expression of syndecan-4 or glypican-1 fourfold. Infection of
      keratinocytes was eliminated by treatment with heparitinase, but not
      phospholipase C, further implicating the syndecan family of integral membrane
      proteins as receptor proteins. Human keratinocytes with a homozygous deletion of
      alpha6 integrin are permissive for HPV11 infection. These results indicate that
      several HSPGs can serve as HPV receptors and support a putative role for syndecan
      1, rather than alpha6 integrin, as a primary receptor protein in natural HPV
      infection of keratinocytes.

PMID- 14645570
TI  - Chromosomal integration and homologous gene targeting by replication-incompetent
      vectors based on the autonomous parvovirus minute virus of mice.
AB  - The molecular mechanisms responsible for random integration and gene targeting by
      recombinant adeno-associated virus (AAV) vectors are largely unknown, and whether
      vectors derived from autonomous parvoviruses transduce cells by similar pathways
      has not been investigated. In this report, we constructed vectors based on the
      autonomous parvovirus minute virus of mice (MVM) that were designed to introduce
      a neomycin resistance expression cassette (neo) into the X-linked human
      hypoxanthine phosphoribosyl transferase (HPRT) locus. High-titer, replication
      incompetent MVM vector stocks were generated with a two-plasmid transfection
      system that preserved the wild-type characteristic of packaging only one DNA
      strand. Vectors with inserts in the forward or reverse orientations packaged
      noncoding or coding strands, respectively. In human HT-1080 cells, MVM vector
      random integration frequencies (neo(+) colonies) were comparable to those
      obtained with AAV vectors, and no difference was observed for noncoding and
      coding strands. HPRT gene-targeting frequencies (HPRT mutant colonies) were lower
      with MVM vectors, and the noncoding strand frequency was threefold greater than
      that of the coding strand. Random integration and gene-targeting events were
      confirmed by Southern blot analysis of G418- and 6-thioguanine (6TG)-resistant
      clones. In separate experiments, correction of an alkaline phosphatase (AP) gene
      by gene targeting was nine times more effective with a coding strand vector. The
      data suggest that single-stranded parvoviral vector genomes are substrates for
      gene targeting and possibly for random integration as well.

PMID- 14645571
TI  - Human immunodeficiency virus type 1 fitness is a determining factor in viral
      rebound and set point in chronic infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) isolates from 20 chronically infected
      patients who participated in a structured treatment interruption (STI) trial were
      studied to determine whether viral fitness influences reestablishment of viremia.
      Viruses derived from individuals who spontaneously controlled viremia had
      significantly lower in vitro replication capacities than viruses derived from
      individuals that did not control viremia after interruption of antiretroviral
      therapy (ART), and replication capacities correlated with pre-ART and post-STI
      viral set points. Of note, no clinically relevant improvement of viral loads upon
      STI occurred. Virus isolates from controlling and noncontrolling patients were
      indistinguishable in terms of coreceptor usage, genetic subtype, and sensitivity
      to neutralizing antibodies. In contrast, viruses from controlling patients
      exhibited increased sensitivity to inhibition by chemokines. Sensitivity to
      inhibition by RANTES correlated strongly with slower replication kinetics of the
      virus isolates, suggesting a marked dependency of these virus isolates on high
      coreceptor densities on the target cells. In summary, our data indicate that
      viral fitness is a driving factor in determining the magnitude of viral rebound
      and viral set point in chronic HIV-1 infection, and thus fitness should be
      considered as a parameter influencing the outcome of therapeutic intervention in
      chronic infection.

PMID- 14645572
TI  - Immunoprotective activity and safety of a respiratory syncytial virus vaccine:
      mucosal delivery of fusion glycoprotein with a CpG oligodeoxynucleotide adjuvant.
AB  - CpG oligodeoxynucleotides (ODN) were identified that stimulated immunoglobulin
      production and cell proliferation in cotton rat cells in vitro. Three of these
      ODN were used as a mucosal adjuvant in the noses of cotton rats immunized via
      this route with respiratory syncytial virus fusion (F) protein. The CpG ODN
      markedly increased the cotton rat humoral neutralizing-antibody response to
      respiratory syncytial virus. Such immunized animals had a marked reduction in the
      production of infectious virus after a live-virus challenge. Animals immunized
      with the combination of F protein and CpG developed enhanced pulmonary pathology
      consisting of alveolitis and interstitial pneumonitis after a live-virus
      challenge. Similar enhanced disease has been seen in cotton rats and children
      immunized with formalin-inactivated respiratory syncytial virus.

PMID- 14645574
TI  - Sequestration of p53 in the cytoplasm by adenovirus type 12 E1B 55-kilodalton
      oncoprotein is required for inhibition of p53-mediated apoptosis.
AB  - The adenovirus E1B 55-kDa protein is a potent inhibitor of p53-mediated
      transactivation and apoptosis. The proposed mechanisms include tethering the E1B
      repression domain to p53-responsive promoters via direct E1B-p53 interaction.
      Cytoplasmic sequestration of p53 by the 55-kDa protein would impose additional
      inhibition on p53-mediated effects. To investigate further the role of
      cytoplasmic sequestration of p53 in its inhibition by the E1B 55-kDa protein we
      systematically examined domains in both the Ad12 55-kDa protein and p53 that
      underpin their colocalization in the cytoplasmic body and show that the N
      terminal transactivation domain (TAD) of p53 is essential for retaining p53 in
      the cytoplasmic body. Deletion of amino acids 11 to 27 or even point mutation
      L22Q/W23S abolished the localization of p53 to the cytoplasmic body, whereas
      other parts of TAD and the C-terminal domain of p53 are dispensable. This
      cytoplasmic body is distinct from aggresome associated with overexpression of
      some proteins, since it neither altered vimentin intermediate filaments nor
      associated with centrosome or ubiquitin. Formation of this structure is sensitive
      to mutation of the Ad12 55-kDa protein. Strikingly, mutation S476/477A near the C
      terminus of the Ad12 55-kDa protein eliminated the formation of the cytoplasmic
      body. The equivalent residues in the Ad5 55-kDa protein were shown to be critical
      for its ability to inhibit p53. Indeed, Ad12 55-kDa mutants that cannot form a
      cytoplasmic body can no longer inhibit p53-mediated effects. Conversely, the Ad12
      55-kDa protein does not suppress p53 mutant L22Q/W23S-mediated apoptosis.
      Finally, we show that E1B can still sequester p53 that contains the mitochondrial
      import sequence, thereby potentially preventing the localization of p53 to
      mitochondria. Thus, cytoplasmic sequestration of p53 by the E1B 55-kDa protein
      plays an important role in restricting p53 activities.

PMID- 14645573
TI  - Protection against murine leukemia virus-induced spongiform myeloencephalopathy
      in mice overexpressing Bcl-2 but not in mice deficient for interleukin-6,
      inducible nitric oxide synthetase, ICE, Fas, Fas ligand, or TNF-R1 genes.
AB  - Some murine leukemia viruses (MuLVs), among them Cas-Br-E and ts-1 MuLVs, are
      neurovirulent, inducing spongiform myeloencephalopathy and hind limb paralysis in
      susceptible mice. It has been shown that the env gene of these viruses harbors
      the determinant of neurovirulence. It appears that neuronal loss occurs by an
      indirect mechanism, since the target motor neurons have not been found to be
      infected. However, the pathogenesis of the disease remains unclear. Several
      lymphokines, cytokines, and other cellular effectors have been found to be
      aberrantly expressed in the brains of infected mice, but whether these are
      required for the development of the neurodegenerative lesions is not known. In an
      effort to identify the specific effectors which are indeed required for the
      initiation and/or development of spongiform myeloencephalopathy, we inoculated
      gene-deficient (knockout [KO]) mice with ts-1 MuLV. We show here that interleukin
      6 (IL-6), inducible nitric oxide synthetase (iNOS), ICE, Fas, Fas ligand (FasL),
      and TNF-R1 KO mice still develop signs of disease. However, transgenic mice
      overexpressing Bcl-2 in neurons (NSE/Bcl-2) were largely protected from hind limb
      paralysis and had less-severe spongiform lesions. These results indicate that
      motor neuron death occurs in this disease at least in part by a Bcl-2-inhibitable
      pathway not requiring the ICE, iNOS, Fas/FasL, TNF-R1, and IL-6 gene products.

PMID- 14645575
TI  - Three-dimensional structures of the A, B, and C capsids of rhesus monkey
      rhadinovirus: insights into gammaherpesvirus capsid assembly, maturation, and DNA
      packaging.
AB  - Rhesus monkey rhadinovirus (RRV) exhibits high levels of sequence homology to
      human gammaherpesviruses, such as Kaposi's sarcoma-associated herpesvirus, and
      grows to high titers in cell cultures, making it a good model system for studying
      gammaherpesvirus capsid structure and assembly. We have purified RRV A, B, and C
      capsids, thus for the first time allowing direct structure comparisons by
      electron cryomicroscopy and three-dimensional reconstruction. The results show
      that the shells of these capsids are identical and are each composed of 12
      pentons, 150 hexons, and 320 triplexes. Structural differences were apparent
      inside the shells and through the penton channels. The A capsid is empty, and its
      penton channels are open. The B capsid contains a scaffolding core, and its
      penton channels are closed. The C capsid contains a DNA genome, which is closely
      packaged into regularly spaced density shells (25 A apart), and its penton
      channels are open. The different statuses of the penton channels suggest a
      functional role of the channels during capsid maturation, and the overall
      structural similarities of RRV capsids to alphaherpesvirus capsids suggest a
      common assembly and maturation pathway. The RRV A capsid reconstruction at a 15-A
      resolution, the best achieved for gammaherpesvirus particles, reveals overall
      structural similarities to alpha- and betaherpesvirus capsids. However, the outer
      regions of the capsid, including densities attributed to the Ta triplex and the
      small capsomer-interacting protein (SCIP or ORF65), exhibit prominent differences
      from their structural counterparts in alphaherpesviruses. This structural
      disparity suggests that SCIP and the triplex, together with tegument and envelope
      proteins, confer structural and potentially functional specificities to alpha-,
      beta-, and gammaherpesviruses.

PMID- 14645576
TI  - Herpes simplex virus 1 mutant in which the ICP0 HUL-1 E3 ubiquitin ligase site is
      disrupted stabilizes cdc34 but degrades D-type cyclins and exhibits diminished
      neurotoxicity.
AB  - Herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0) is a
      multifunctional protein that functions as a promiscuous transactivator and
      promotes the degradation of multiple cellular proteins. In vitro studies
      indicated that it encodes two physically separated functional E3 ubiquitin ligase
      domains. One, designated herpesvirus ubiquitin ligase 1 (HUL-1), maps to a region
      encoded by exon 3 and is contained between residues 543 and 680. Deletion of
      amino acids 621 to 625 abolishes this activity. The second, designated HUL-2,
      maps to the RING finger domain present in ICP0 encoded by exon 2. Earlier studies
      have shown that ICP0 stabilizes cyclins D1 and D3, and several lines of
      investigation led to the hypothesis that this function of ICP0 is the consequence
      of degradation of the E2 enzyme cdc34, known to be involved in the proteasome
      dependent degradation of D-type cyclins. Consistent with this hypothesis, we have
      previously shown that cdc34 physically interacts with ICP0 at or near aspartate
      199 and at amino acids 621 to 625 and that the former site is required for
      effective ubiquitylation and degradation of cdc34. Furthermore, the ICP0 HUL-1
      domain promotes the polyubiquitination of cdc34 in vitro. If the mechanism by
      which D-type cyclins are salvaged in wild-type-infected cells is dependent on
      polyubiquitination and consequent destruction of cdc34, than the mutant virus
      R6701, which was constructed for these studies and lacks ICP0 residues 621 to
      625, should destabilize the D cyclins and preclude the degradation of cdc34. We
      report that ICP0 residues 621 to 625 are essential for degradation of cdc34 in
      infected cells and for the ICP0-mediated stabilization of D-type cyclins, that a
      mutation that specifically disrupted the ring finger domain of the HUL-2 site had
      no effect on the degradation of cdc34 in infected cells, and that deletion of
      ICP0 residues 621 to 625 decreased the replicative capacity of the virus in
      growth-arrested but not in dividing cells and resulted in diminished
      pathogenicity on intracerebral inoculation of mice. We conclude that the ICP0 HUL
      1 domain acts in infected cells to degrade cdc34 and that this function requires
      the interaction of cdc34 with sequences in exons 2 and 3 but does not involve the
      HUL-2 RING finger E3 domain.

PMID- 14645577
TI  - Infection and injury of neurons by West Nile encephalitis virus.
AB  - West Nile virus (WNV) infects neurons and leads to encephalitis, paralysis, and
      death in humans, animals, and birds. We investigated the mechanism by which
      neuronal injury occurs after WNV infection. Neurons in the anterior horn of the
      spinal cords of paralyzed mice exhibited a high degree of WNV infection,
      leukocyte infiltration, and degeneration. Because it was difficult to distinguish
      whether neuronal injury was caused by viral infection or by the immune system
      response, a novel tissue culture model for WNV infection was established in
      neurons derived from embryonic stem (ES) cells. Undifferentiated ES cells were
      relatively resistant to WNV infection. After differentiation, ES cells expressed
      neural antigens, acquired a neuronal phenotype, and became permissive for WNV
      infection. Within 48 h of exposure to an exceedingly low multiplicity of
      infection (5 x 10(-4)), 50% of ES cell-derived neurons became infected, producing
      nearly 10(7) PFU of infectious virus per ml, and began to die by an apoptotic
      mechanism. The establishment of a tractable virus infection model in ES cell
      derived neurons facilitates the study of the molecular basis of neurotropism and
      the mechanisms of viral and immune-mediated neuronal injury after infection by
      WNV or other neurotropic pathogens.

PMID- 14645578
TI  - Mechanisms governing maintenance of Cdk1/cyclin B1 kinase activity in cells
      infected with human cytomegalovirus.
AB  - Previous work has demonstrated dysregulation of key cell cycle components in
      human cytomegalovirus (HCMV)-infected human fibroblasts, resulting in cell cycle
      arrest (F. M. Jault, J.-M. Jault, F. Ruchti, E. A. Fortunato, C. L. Clark, J.
      Corbeil, D. D. Richman, and D. H. Spector, J. Virol. 69:6697-6704, 1995). The
      activation of the mitotic kinase Cdk1/cyclin B, which was detected as early as 8
      h postinfection (p.i.) and maintained throughout the time course, was
      particularly interesting. To understand the mechanisms underlying the induction
      of this kinase activity, we have examined the pathways that regulate the
      activation of Cdk1/cyclin B1 complexes. The accumulation of the cyclin B1 subunit
      in HCMV-infected cells is the result of increased synthesis and reduced
      degradation of the protein. In addition, the catalytic subunit, Cdk1, accumulates
      in its active form in virus-infected cells. The decreased level of the Tyr15
      phosphorylated form of Cdk1 in virus-infected fibroblasts is due in part to the
      down-regulation of the expression and activity of the Cdk1 inhibitory kinases
      Myt1 and Wee1. Increased degradation of Wee1 via the proteasome also accounts for
      its absence at 24 h p.i. At late times, we observed accumulation of the Cdc25
      phosphatases that remove the inhibitory phosphates from Cdk1. Interestingly,
      biochemical fractionation studies revealed that the active form of Cdk1, a
      fraction of total cyclin B1, and the Cdc25 phosphatases reside predominantly in
      the cytoplasm of infected cells. Collectively, these data suggest that the
      maintenance of Cdk1/cyclin B1 activity observed in HCMV-infected cells can be
      explained by three mechanisms: the accumulation of cyclin B1, the inactivation of
      negative regulatory pathways for Cdk1, and the accumulation of positive factors
      that promote Cdk1 activity.

PMID- 14645579
TI  - Mechanism of action and antiviral activity of benzimidazole-based allosteric
      inhibitors of the hepatitis C virus RNA-dependent RNA polymerase.
AB  - The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is the catalytic
      subunit of the viral RNA amplification machinery and is an appealing target for
      the development of new therapeutic agents against HCV infection. Nonnucleoside
      inhibitors based on a benzimidazole scaffold have been recently reported.
      Compounds of this class are efficient inhibitors of HCV RNA replication in cell
      culture, thus providing attractive candidates for further development. Here we
      report the detailed analysis of the mechanism of action of selected benzimidazole
      inhibitors. Kinetic data and binding experiments indicated that these compounds
      act as allosteric inhibitors that block the activity of the polymerase prior to
      the elongation step. Escape mutations that confer resistance to these compounds
      map to proline 495, a residue located on the surface of the polymerase thumb
      domain and away from the active site. Substitution of this residue is sufficient
      to make the HCV enzyme and replicons resistant to the inhibitors. Interestingly,
      proline 495 lies in a recently identified noncatalytic GTP-binding site, thus
      validating it as a potential allosteric site that can be targeted by small
      molecule inhibitors of HCV polymerase.

PMID- 14645580
TI  - Signals that dictate nuclear localization of human papillomavirus type 16
      oncoprotein E6 in living cells.
AB  - Human papillomavirus (HPV) type 16 E6 (16E6) is an oncogenic, multifunctional
      nuclear protein that induces p53 degradation and perturbs normal cell cycle
      control, leading to immortalization and transformation of infected keratinocytes
      and epithelial cells. Although it is unclear how 16E6 disrupts the epigenetic
      profile of host genes, its presence in the nucleus is a key feature. The present
      report describes intrinsic properties of 16E6 that influence its nuclear import
      in living cells. When the coding region of full-length 16E6 was inserted in frame
      into the C terminus of green fluorescent protein (GFP), it effectively prevented
      the 16E6 pre-mRNA from being spliced and led to the expression of a GFP-E6 fusion
      which localized predominantly to the nucleus. Further studies identified three
      novel nuclear localization signals (NLSs) in 16E6 that drive the protein to
      accumulate in the nucleus. We found that all three NLS sequences are rich in
      positively charged basic residues and that point mutations in these key residues
      could abolish the retention of 16E6 in the nucleus as well as the p53 degradation
      and cell immortalization activities of the protein. When inserted into
      corresponding regions of low-risk HPV type 6 E6, the three NLS sequences
      described for 16E6 functioned actively in converting the normally cytoplasmic HPV
      type 6 E6 into a nuclear protein. The separate NLS sequences, however, appear to
      play different roles in nuclear import and retention of HPV E6. The discovery of
      three unique NLS sequences in 16E6 provides new insights into the nuclear
      association of 16E6 which may reveal other novel activities of this important
      oncogenic protein.

PMID- 14645581
TI  - Intravenous inoculation of replication-deficient recombinant vaccinia virus DIs
      expressing simian immunodeficiency virus gag controls highly pathogenic simian
      human immunodeficiency virus in monkeys.
AB  - To be effective, a vaccine against human immunodeficiency virus type 1 (HIV-1)
      must induce virus-specific T-cell responses and it must be safe for use in
      humans. To address these issues, we developed a recombinant vaccinia virus DIs
      vaccine (rDIsSIVGag), which is nonreplicative in mammalian cells and expresses
      the full-length gag gene of simian immunodeficiency virus (SIV). Intravenous
      inoculation of 10(6) PFU of rDIsSIVGag in cynomologus macaques induced
      significant levels of gamma interferon (IFN-gamma) spot-forming cells (SFC)
      specific for SIV Gag. Antigen-specific lymphocyte proliferative responses were
      also induced and were temporally associated with the peak of IFN-gamma SFC
      activity in each macaque. In contrast, macaques immunized with a vector control
      (rDIsLacZ) showed no significant induction of antigen-specific immune responses.
      After challenge with a highly pathogenic simian-human immunodeficiency virus
      (SHIV), CD4(+) T lymphocytes were maintained in the peripheral blood and lymphoid
      tissues of the immunized macaques. The viral set point in plasma was also reduced
      in these animals, which may be related to the enhancement of virus-specific
      intracellular IFN-gamma(+) CD8(+) cell numbers and increased antibody titers
      after SHIV challenge. These results demonstrate that recombinant DIs has
      potential for use as an HIV/AIDS vaccine.

PMID- 14645582
TI  - A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein
      induces high levels of beta interferon and is attenuated in mice.
AB  - Previously we found that the amino-terminal region of the NS1 protein of
      influenza A virus plays a key role in preventing the induction of beta interferon
      (IFN-beta) in virus-infected cells. This region is characterized by its ability
      to bind to different RNA species, including double-stranded RNA (dsRNA), a known
      potent inducer of IFNs. In order to investigate whether the NS1 RNA-binding
      activity is required for its IFN antagonist properties, we have generated a
      recombinant influenza A virus which expresses a mutant NS1 protein defective in
      dsRNA binding. For this purpose, we substituted alanines for two basic amino
      acids within NS1 (R38 and K41) that were previously found to be required for RNA
      binding. Cells infected with the resulting recombinant virus showed increased IFN
      beta production, demonstrating that these two amino acids play a critical role in
      the inhibition of IFN production by the NS1 protein during viral infection. In
      addition, this virus grew to lower titers than wild-type virus in MDCK cells, and
      it was attenuated in mice. Interestingly, passaging in MDCK cells resulted in the
      selection of a mutant virus containing a third mutation at amino acid residue 42
      of the NS1 protein (S42G). This mutation did not result in a gain in dsRNA
      binding activity by the NS1 protein, as measured by an in vitro assay.
      Nevertheless, the NS1 R38AK41AS42G mutant virus was able to replicate in MDCK
      cells to titers close to those of wild-type virus. This mutant virus had
      intermediate virulence in mice, between those of the wild-type and parental NS1
      R38AK41A viruses. These results suggest not only that the IFN antagonist
      properties of the NS1 protein depend on its ability to bind dsRNA but also that
      they can be modulated by amino acid residues not involved in RNA binding.

PMID- 14645583
TI  - Lytic viral replication as a contributor to the detection of Epstein-Barr virus
      in breast cancer.
AB  - Epstein-Barr virus (EBV) has an accepted association with the epithelial
      malignancy nasopharyngeal carcinoma and has also been reported in other more
      controversial carcinoma settings. Evaluation of EBV association with epithelial
      carcinomas such as breast cancer would benefit from a better understanding of the
      outcome of EBV infection of these cells. Cell-free preparations of a green
      fluorescent protein-expressing virus, BX1, were used to infect breast cancer cell
      lines, which were then examined for EBV gene expression and viral genome copy
      number. Reverse transcription-PCR analyses revealed that the cells supported a
      mixture of latency II and lytic EBV gene expression. Lytic Zta and BMRF1 protein
      expression was detected by immunohistochemistry, and DNA PCR analyses estimated
      an EBV copy number of 300 to 600 genomes per infected cell. Evidence for lytic
      EBV expression was also found in breast tissue, where reverse transcription-PCR
      analyses detected lytic Zta transcripts in 7 of 10 breast carcinoma tissues and 4
      of 10 normal tissues from the same patients. Scattered cells immunoreactive for
      Zta protein were also detectable in breast carcinoma. Quantitative real-time PCR
      analysis of EBV-positive breast carcinoma tissues suggested that less than 0.1%
      of the cells contained viral genomes. We suggest that sporadic lytic EBV
      infection may contribute to PCR-based detection of EBV in traditionally
      nonvirally associated epithelial malignancies.

PMID- 14645584
TI  - Association of adenovirus with the microtubule organizing center.
AB  - Adenoviruses (Ad) must deliver their genomes to the nucleus of the target cell to
      initiate an infection. Following entry into the cell and escape from the
      endosome, Ad traffics along the microtubule cytoskeleton toward the nucleus. In
      the final step in Ad trafficking, Ad must leave the microtubule and establish an
      association with the nuclear envelope. We hypothesized that in cells lacking a
      nucleus, the capsid moves to and associates with the microtubule organizing
      center (MTOC). To test this hypothesis, we established an experimental system to
      examine Ad trafficking in enucleated cells compared to Ad trafficking in intact,
      mock-enucleated cells. Enucleation of a monolayer of A549 human lung epithelial
      cells was accomplished by depolymerization of the actin cytoskeleton followed by
      centrifugation. Upon infection of enucleated cells with Cy3-labeled Ad, the
      majority of Ad capsid trafficked to a discrete, centrally located site which
      colocalized with pericentrin, a component of the MTOC. MTOC-associated Ad had
      escaped from endosomes and thus had direct access to MTOC components. Ad
      localization at this site was sensitive to the microtubule-depolymerizing agent
      nocodazole, but not to the microfilament-depolymerizing agent cytochalasin B,
      indicating that intact microtubules were required to maintain the localization
      with the MTOC. Ad localization to the MTOC in the enucleated cells was stable, as
      demonstrated by continuing Ad localization with pericentrin for more than 5 h
      after infection, a strong preference for Ad arrival at rather than Ad departure
      from the MTOC, and minimal redistribution of Ad between MTOCs within a single
      cell. In summary, the data demonstrate that the Ad capsid establishes a stable
      interaction with the MTOC when a nucleus is not present, suggesting that
      dissociation of Ad from microtubules likely requires nuclear factors.

PMID- 14645585
TI  - Dendritic cells harbor infectious porcine circovirus type 2 in the absence of
      apparent cell modulation or replication of the virus.
AB  - Dendritic cells (DCs) play crucial roles in innate and adaptive immune responses,
      rendering them critical targets for virus infections. Porcine circovirus type 2
      (PCV2) is associated with the development of postweaning multisystemic wasting
      syndrome (PMWS) in piglets. We demonstrate here that 80 to 90% of monocyte
      derived and bone marrow-derived DCs interact with PCV2 similar to the early
      stages of an infection. There was no evidence for virus replication, but the
      virus did persist in DCs without loss of infectivity nor the induction of cell
      death. This could reflect an abortive infection, but there was no evidence of
      virus uncoating-the infectivity remained intact for at least 5 days.
      Alternatively, the results may reflect DC endocytosis of antigenic material.
      However, there was no modulation of DC surface major histocompatibility complex
      class I and class II, CD80/86, CD25, CD16, or CD14. Furthermore, infected DC did
      not transmit virus to syngeneic T lymphocytes, even when the latter were
      activated. Such coculture did not induce PCV2 replication or death of the
      lymphocytes or DCs. These results demonstrate that PCV2 can persist in DCs in the
      absence of virus replication or degradation. Such a silent virus infection
      presents a novel mechanism of not only immune evasion but also escaping the DC
      degradation pathway. Because of their migratory capacity, infection of DCs thus
      provides a potent vehicle for transport of the virus throughout the host without
      the need for replication. In addition, the lymphopenia seen in PMWS is not a
      direct effect of the virus on lymphocytes but would require additional events, as
      proposed by others.

PMID- 14645586
TI  - Human cytomegalovirus transmission from the uterus to the placenta correlates
      with the presence of pathogenic bacteria and maternal immunity.
AB  - Prenatal cytomegalovirus infection may cause pregnancy complications such as
      intrauterine growth restriction and birth defects. How virus from the mother
      traverses the placenta is unknown. PCR analysis of biopsy specimens of the
      maternal-fetal interface revealed that DNA sequences from cytomegalovirus were
      commonly found with those of herpes simplex viruses and pathogenic bacteria.
      Cytomegalovirus DNA and infected cell proteins were found more often in the
      decidua than in the placenta, suggesting that the uterus functions as a reservoir
      for infection. In women with low neutralizing titers, cytomegalovirus replicated
      in diverse decidual cells and placental trophoblasts and capillaries. In women
      with intermediate to high neutralizing titers, decidual infection was suppressed
      and the placenta was spared. Overall, cytomegalovirus virions and maternal
      immunoglobulin G were detected in syncytiotrophoblasts, villus core macrophages,
      and dendritic cells. These results suggest that the outcome of cytomegalovirus
      infection depends on the presence of other pathogens and coordinated immune
      responses to viral replication at the maternal-fetal interface.

PMID- 14645587
TI  - Novel system for the simultaneous analysis of geminivirus DNA replication and
      plant interactions in Nicotiana benthamiana.
AB  - The origin of replication of African cassava mosaic virus (ACMV) and a gene
      expression vector based on Potato virus X were exploited to devise an in planta
      system for functional analysis of the geminivirus replication-associated protein
      (Rep) in transgenic Nicotiana benthamiana line pOri-2. This line contains an
      integrated copy of a tandem repeat of the ACMV origin of replication flanking
      nonviral sequences that can be mobilized and replicated by Rep as an episomal
      replicon. A Rep-GFP fusion protein can also mobilize and amplify the replicon,
      facilitating Rep detection in planta. The activity of Rep and its mutants, Rep
      mediated host response, and the correlation between Rep intracellular
      localization and biological functions could be effectively assessed by using this
      in planta system. Our results indicate that modification of amino acid residues
      R(2), R(5), R(7) and K(11) or H(56), L(57) and H(58) prevent Rep function in
      replication. This defect correlates with possible loss of Rep nuclear
      localization and inability to trigger the host defense mechanism resembling a
      hypersensitive response.

PMID- 14645588
TI  - CD8+ T cells mediate recovery and immunopathology in West Nile virus
      encephalitis.
AB  - C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus
      (WNV) develop a characteristic central nervous system (CNS) disease, including an
      acute inflammatory reaction. Dose response studies indicate two distinct kinetics
      of mortality. At high doses of infection (10(8) PFU), direct infection of the
      brain occurred within 24 h, resulting in 100% mortality with a 6-day mean
      survival time (MST), and there was minimal destruction of neural tissue. A low
      dose (10(3) PFU) of infection resulted in 27% mortality (MST, 11 days), and virus
      could be detected in the CNS 7 days postinfection (p.i.). Virus was present in
      the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the
      brains revealed neuronal degeneration and inflammation within leptomeninges and
      brain parenchyma. Inflammatory cell infiltration was detectable in brains from
      day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose
      group, with the severity of infiltration increasing over time. The cellular
      infiltrates in brain consisted predominantly of CD8(+), but not CD4(+), T cells.
      CD8(+) T cells in the brain and the spleen expressed the activation markers CD69
      early and expressed CD25 at later time points. CD8(+) T-cell-deficient mice
      infected with 10(3) PFU of WNV showed increased mortalities but prolonged MST and
      early infection of the CNS compared to wild-type mice. Using high doses of virus
      in CD8-deficient mice leads to increased survival. These results provide evidence
      that CD8(+) T cells are involved in both recovery and immunopathology in WNV
      infection.

PMID- 14645589
TI  - Complete genomic sequence and comparative analysis of the tumorigenic poxvirus
      Yaba monkey tumor virus.
AB  - The Yatapoxvirus genus of poxviruses is comprised of Yaba monkey tumor virus
      (YMTV), Tanapox virus, and Yaba-like disease virus (YLDV), which all have the
      ability to infect primates, including humans. Unlike other poxviruses, YMTV
      induces formation of focalized histiocytomas upon infection. To gain a greater
      understanding of the Yatapoxvirus genus and the unique tumor formation properties
      of YMTV, we sequenced the 134,721-bp genome of YMTV. The genome of YMTV encodes
      at least 140 open reading frames, all of which are also found as orthologs in the
      closely related YLDV. However, 13 open reading frames found in YLDV are
      completely absent from YMTV. Common to both YLDV and YMTV are the unusually large
      noncoding regions between many open reading frames. To determine whether any of
      these noncoding regions might be functionally significant, we carried out a
      comparative analysis between the putative noncoding regions of YMTV and similar
      noncoding regions from other poxviruses. This approach identified three new gene
      poxvirus families, defined as orthologs of YMTV23.5L, YMTV28.5L, and YMTV120.5L,
      which are highly conserved in virtually all poxvirus species. Furthermore, the
      comparative analysis also revealed a 40-bp nucleotide sequence at approximately
      14,700 bases from the left terminus that was 100% identical in the comparable
      intergene site within members of the Yatapoxvirus, Suipoxvirus, and Capripoxvirus
      genera and 95% conserved in the Leporipoxvirus genus. This conserved sequence was
      shown to function as a poxvirus late promoter element in transfected and infected
      cells, but other functions, such as an involvement in viral replication or
      packaging, cannot be excluded. Finally, we summarize the predicted
      immunomodulatory protein repertoire in the Yatapoxvirus genus as a whole.

PMID- 14645590
TI  - Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase
      viral replication but fail in long-term control of simian immunodeficiency virus
      SIVmac239.
AB  - Given the current difficulties generating vaccine-induced neutralizing antibodies
      to human immunodeficiency virus (HIV), the focus of the vaccine community has
      shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent
      reports of CTL-based vaccine trials in macaques challenged with simian/human
      immunodeficiency virus SHIV-89.6P have supported the notion that such vaccines
      can ameliorate the course of disease. However, almost all of these studies
      included Env as an immunogen and since SHIV-89.6P is sensitive to neutralizing
      antibodies it is difficult to determine the mechanism(s) of protection.
      Consequently, SHIV-89.6P challenge of macaques may be a poor model for
      determining vaccine efficacy in humans. To ascertain the effect of vaccine
      induced multispecific mucosal CTL, in the absence of Env-specific antibody, on
      the control of an immunodeficiency virus challenge, we vaccinated Mamu-A*01(+)
      macaques with constructs encoding a combination of CTL epitopes and full-length
      proteins (Tat, Rev, and Nef) by using a DNA prime/recombinant modified vaccinia
      virus Ankara (rMVA) boost regimen. The vaccination induced virus-specific CTL and
      CD4(+) helper T lymphocytes with CTL frequencies as high as 20,000/million
      peripheral blood mononuclear cells. The final rMVA vaccination, delivered
      intravenously, engendered long-lived mucosal CTL. At 16 weeks after the final
      rMVA vaccination, the vaccinees and naive, Mamu-A*01(+) controls were challenged
      intrarectally with SIVmac239. Massive early anamnestic cellular immune responses
      controlled acute-phase viral replication; however, the three vaccinees were
      unable to control virus replication in the chronic phase. The present study
      suggests that multispecific mucosal CTL, in the absence of neutralizing
      antibodies, can achieve a modicum of control over early viral replication but are
      unable to control chronic-phase viral replication after a high-dose mucosal
      challenge with a pathogenic simian immunodeficiency virus.

PMID- 14645591
TI  - The delta region of outer-capsid protein micro 1 undergoes conformational change
      and release from reovirus particles during cell entry.
AB  - Cell entry by reoviruses requires a large, transcriptionally active subvirion
      particle to gain access to the cytoplasm. The features of this particle have been
      the subject of debate, but three primary candidates-the infectious subvirion
      particle (ISVP), ISVP*, and core particle forms-that differ in whether putative
      membrane penetration protein micro 1 and adhesin sigma1 remain particle bound
      have been identified. Experiments with antibody reagents in this study yielded
      new information about the steps in particle disassembly during cell entry.
      Monoclonal antibodies specific for the delta region of micro 1 provided evidence
      for a conformational change in micro 1 and for release of the delta proteolytic
      fragment from entering particles. Antiserum raised against cores provided
      evidence for entry-related changes in particle structure and identified entering
      particles that largely lack the delta fragment inside cells. Antibodies specific
      for sigma1 showed that it is also largely shed from entering particles. Limited
      coimmunostaining with markers for late endosomes and lysosomes indicated the
      particles lacking delta and sigma1 did not localize to those subcellular
      compartments, and other observations suggested that both the particles and free
      delta were released into the cytoplasm. Essentially equivalent findings were
      obtained with native ISVPs and highly infectious recoated particles containing
      wild-type proteins. Poorly infectious recoated particles containing a hyperstable
      mutant form of micro 1, however, showed no evidence for the in vitro and
      intracellular changes in particle structure normally detected by antibodies, and
      these particles instead accumulated in late endosomes or lysosomes. Recoated
      particles with hyperstable micro 1 were also ineffective at mediating erythrocyte
      lysis in vitro and promoting alpha-sarcin coentry and intoxication of cells in
      cultures. Based on these and other findings, we propose that ISVP* is a transient
      intermediate in cell entry which mediates membrane penetration and is then
      further uncoated in the cytoplasm to yield particles, resembling cores, that
      largely lack the delta fragment of micro 1.

PMID- 14645593
TI  - Alpha interferon inhibits human T-cell leukemia virus type 1 assembly by
      preventing Gag interaction with rafts.
AB  - Alpha-2a interferon (IFN-alpha2a) has beneficial clinical effects on human T-cell
      leukemia virus type 1 (HTLV-1) infection, but its antiviral mechanism of action
      is unknown. Antiviral effects of IFN-alpha2a were studied in 293T cells
      expressing HTLV-1 proviral DNA and in HTLV-1-infected cells (HOS/PL, MT2, and
      HUT102). In 293T cells, an 50% inhibitory concentration of 10 U of IFN-alpha2a/ml
      was determined by p19 antigen ELISA. Analysis of IFN-treated cells demonstrated
      no defect in viral protein synthesis but did show a decrease in the level of
      released virus, as determined by immunoblot assays. Electron microscopy studies
      of IFN-treated cells revealed neither a defect in the site of virus budding nor
      tethering of virus particles at the plasma membrane, thus arguing against an
      effect on virus release. Cell fractionation studies and confocal microscopy
      showed no effect of IFN on Gag association with membranes. However, the level of
      Gag association with lipid rafts was decreased, suggesting a role of IFN in
      inhibiting HTLV-1 assembly.

PMID- 14645594
TI  - Neutralization of enteric coronaviruses with Escherichia coli cells expressing
      single-chain Fv-autotransporter fusions.
AB  - We report here that fusions of single-chain antibodies (scFvs) to the
      autotransporter beta domain of the IgA protease of Neisseria gonorrhoeae are
      instrumental in locating virus-neutralizing activity on the cell surface of
      Escherichia coli. E. coli cells displaying scFvs against the transmissible
      gastroenteritis coronavirus on their surface blocked in vivo the access of the
      infectious agent to cultured epithelial cells. This result raises prospects for
      antiviral strategies aimed at hindering the entry into target cells by bacteria
      that naturally colonize the same intestinal niches.

PMID- 14645595
TI  - Sequence analysis of recent H7 avian influenza viruses associated with three
      different outbreaks in commercial poultry in the United States.
AB  - The hemagglutinin (HA) and neuraminidase (NA) genes of H7 avian influenza virus
      (AIV) isolated between 1994 and 2002 from live-bird markets (LBMs) in the
      northeastern United States and from three outbreaks in commercial poultry have
      been characterized. Phylogenetic analysis of the HA and NA genes demonstrates
      that the isolates from commercial poultry were closely related to the viruses
      circulating in the LBMs. Also, since 1994, two distinguishing genetic features
      have appeared in this AIV lineage: a deletion of 17 amino acids in the NA protein
      stalk region and a deletion of 8 amino acids in the HA1 protein which is
      putatively in part of the receptor binding site. Furthermore, analysis of the HA
      cleavage site amino acid sequence, a marker for pathogenicity in chickens and
      turkeys, shows a progression toward a cleavage site sequence that fulfills the
      molecular criteria for highly pathogenic AIV.

PMID- 14645596
TI  - Characterization of murine leukemia virus restriction in mammals.
AB  - Restriction of murine leukemia virus (MLV) was examined in cells from a range of
      mammals. All nonmurine restrictions were saturable blocks to N-tropic MLV
      infection, and several were prior to reverse transcription. We demonstrate
      restriction in cells from bat and show that if we express the murine restriction
      factor Fv1 in human cells, then Fv1, not the human host, defines the stage at
      which infection is blocked.

PMID- 14645597
TI  - Detailed analysis of the CD8+ T-cell response following adenovirus vaccination.
AB  - We examined CD8(+) T-cell expansion and function following intramuscular
      immunization with a recombinant adenovirus. This study has identified a number of
      properties which may explain the strong immunogenicity of adenovirus vectors: (i)
      the ability to deliver large amounts of antigen into the lymphoid tissues, (ii)
      the ability to induce rapid expansion and migration of CD8(+) T cells throughout
      the lymphatics, and (iii) the ability to produce a sustained, high-level CD8(+) T
      cell response.

PMID- 14645598
TI  - Human immunodeficiency virus type 1 DNA nuclear import and integration are
      mitosis independent in cycling cells.
AB  - An essential step in human immunodeficiency virus type 1 (HIV-1) replication is
      the movement of the viral preintegration complex from the cytoplasm into the
      nucleus. The pathway(s) and timing for HIV-1 DNA nuclear entry in cycling cells
      have not been established. Here, we show that if cycling cells are infected
      before S phase, viral DNA can be integrated prior to passage of the host DNA
      replication fork through the integration site, as indicated by stable inheritance
      in both daughter cells. We conclude that efficient nuclear entry can occur
      independently of mitotic nuclear disassembly in cycling cells.

PMID- 14645592
TI  - Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4
      transition by motif analysis of human immunodeficiency virus type 1 env V3 loop
      sequences.
AB  - Early in infection, human immunodeficiency virus type 1 (HIV-1) generally uses
      the CCR5 chemokine receptor (along with CD4) for cellular entry. In many HIV-1
      infected individuals, viral genotypic changes arise that allow the virus to use
      CXCR4 (either in addition to CCR5 or alone) as an entry coreceptor. This switch
      has been associated with an acceleration of both CD3(+) T-cell decline and
      progression to AIDS. While it is well known that the V3 loop of gp120 largely
      determines coreceptor usage and that positively charged residues in V3 play an
      important role, the process of genetic change in V3 leading to altered coreceptor
      usage is not well understood. Further, the methods for biological phenotyping of
      virus for research or clinical purposes are laborious, depend on sample
      availability, and present biosafety concerns, so reliable methods for sequence
      based "virtual phenotyping" are desirable. We introduce a simple bioinformatic
      method of scoring V3 amino acid sequences that reliably predicts CXCR4 usage
      (sensitivity, 84%; specificity, 96%). This score (as determined on the basis of
      position-specific scoring matrices [PSSM]) can be interpreted as revealing a
      propensity to use CXCR4 as follows: known R5 viruses had low scores, R5X4 viruses
      had intermediate scores, and X4 viruses had high scores. Application of the PSSM
      scoring method to reconstructed virus phylogenies of 11 longitudinally sampled
      individuals revealed that the development of X4 viruses was generally gradual and
      involved the accumulation of multiple amino acid changes in V3. We found that X4
      viruses were lost in two ways: by the dying off of an established X4 lineage or
      by mutation back to low-scoring V3 loops.

PMID- 14645599
TI  - Expression of unmodified hepatitis C virus envelope glycoprotein-coding sequences
      leads to cryptic intron excision and cell surface expression of E1/E2
      heterodimers comprising full-length and partially deleted E1.
AB  - Hepatitis C virus (HCV) is a positive-strand RNA virus that replicates
      exclusively in the cytoplasm of infected cells. The viral envelope glycoproteins,
      E1 and E2, appear to be retained in the endoplasmic reticulum, where viral
      budding is thought to occur. Surprisingly, we found that the expression system
      used to generate HCV envelope glycoproteins influences their subcellular
      localization and processing. These findings have important implications for
      optimizing novel HCV fusion and entry assays as well as for budding and virus
      particle formation.

PMID- 14645600
TI  - Identification of proteins associated with murine gammaherpesvirus 68 virions.
AB  - Murine gammaherpesvirus 68 (MHV68 [also known as gammaHV-68]) is distinguished by
      its ability to replicate to high titers in cultured cells, making it an excellent
      candidate for studying gammaherpesvirus virion composition. Extracellular MHV68
      virions were isolated, and abundant virion-associated proteins were identified by
      mass spectrometry. Five nucleocapsid protein homologues, the tegument protein
      homologue encoded by open reading frame (ORF) 75c, and envelope glycoproteins B
      and H were detected. In addition, gene products from MHV68 ORF20, ORF24, ORF28,
      ORF45, ORF48, and ORF52 were identified in association with virions, suggesting
      that these gammaherpesvirus genes are involved in the early phase of infection or
      virion assembly and egress.

PMID- 14645601
TI  - Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein
      mediated viral infection.
AB  - Folate receptor alpha (FRalpha) has been described as a factor involved in
      mediating Ebola virus entry into cells (6). Furthermore, it was suggested that
      interaction with FRalpha results in internalization and subsequent viral ingress
      into the cytoplasm via caveolae (9). Descriptions of cellular receptors for Ebola
      virus and its entry mechanisms are of fundamental importance, particularly with
      the advent of vectors bearing Ebola virus glycoprotein (GP) being utilized for
      gene transfer into cell types such as airway epithelial cells. Thus, the ability
      of FRalpha to mediate efficient entry of viral pseudotypes carrying GP was
      investigated. We identified cell lines and primary cell types such as macrophages
      that were readily infected by GP pseudotypes despite lacking detectable surface
      FRalpha, indicating that this receptor is not essential for Ebola virus
      infection. Furthermore, we find that T-cell lines stably expressing FRalpha are
      not infectible, suggesting that FRalpha is also not sufficient to mediate entry.
      T-cell lines lack caveolae, the predominant route of FRalpha-mediated folate
      metabolism. However, the coexpression of FRalpha with caveolin-1, the major
      structural protein of caveolae, was not able to rescue infectivity in a T-cell
      line. In addition, other cell types lacking caveolae are fully infectible by GP
      pseudotypes. Finally, a panel of ligands to and soluble analogues of FRalpha were
      unable to inhibit infection on a range of cell lines, questioning the role of
      FRalpha as an important factor for Ebola virus entry.

PMID- 14645602
TI  - De novo infection with rhesus monkey rhadinovirus leads to the accumulation of
      multiple intranuclear capsid species during lytic replication but favors the
      release of genome-containing virions.
AB  - Rhesus monkey rhadinovirus (RRV) is one of the closest phylogenetic relatives to
      the human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), yet it has the
      distinct experimental advantage of entering efficiently into lytic replication
      and growing to high titers in culture. RRV therefore holds promise as a
      potentially attractive model with which to study gammaherpesvirus structure and
      assembly. We have isolated RRV capsids, determined their molecular composition,
      and identified the genes encoding five of the main capsid structural proteins.
      Our data indicate that, as with other herpesviruses, lytic infection with RRV
      leads to the synthesis of three distinct intranuclear capsid species. However, in
      contrast to the inefficiency of KSHV maturation following reactivation from
      latently infected B-cell lines (K. Nealon, W. W. Newcomb, T. R. Pray, C. S.
      Craik, J. C. Brown, and D. H. Kedes, J. Virol. 75:2866-2878, 2001), de novo
      infection of immortalized rhesus fibroblasts with RRV results in the release of
      high levels of infectious virions with genome-containing C capsids at their
      center. Together, our findings argue for the use of RRV as a powerful model with
      which to study the structure and assembly of gammaherpesviruses and,
      specifically, the human rhadinovirus,KSHV.

PMID- 14645603
TI  - Integrin alpha3beta1 is an alternative cellular receptor for adenovirus serotype
      5.
AB  - Many adenovirus serotypes enter cells by high-affinity binding to the
      coxsackievirus-adenovirus receptor (CAR) and integrin-mediated internalization.
      In the present study, we analyzed the possible receptor function of alpha3beta1
      for adenovirus serotype 5 (Ad5). We found that penton base and integrin
      alpha3beta1 could interact in vitro. In vivo, both Ad5-cell binding and virus
      mediated transduction were inhibited in the presence of anti-alpha3 and anti
      beta1 function-blocking antibodies, and this occurred in both CAR-positive and
      CAR-negative cell lines. Peptide library screenings and data from binding
      experiments with wild-type and mutant penton base proteins suggest that the Arg
      Gly-Asp (RGD) in the penton base protein, the best known integrin binding motif,
      is only part of the binding interface with alpha3beta1, which involved multiple
      additional contact sites.

PMID- 14645604
TI  - The James Lind Initiative.

PMID- 14645605
TI  - Depression--the hidden symptom in advanced cancer.

PMID- 14645606
TI  - Hyperacusis.

PMID- 14645607
TI  - Diagnosis of abdominal tuberculosis: the importance of laparoscopy.
AB  - Abdominal tuberculosis (TB) tends to present with non-specific features and can
      be hard to diagnose. In the University Hospitals of Leicester, which serve a
      large immigrant population, 36 patients had this diagnosis between 1995 and 2001.
      We examined their records to identify features, including history, clinical
      presentation, investigations and diagnostic procedures, that might help with
      diagnosis of future cases. 32 of the patients were of Asian origin, predominantly
      from the Indian subcontinent. The most common presenting complaints were
      abdominal pain and weight loss. On clinical examination the findings were non
      specific. Only 2 patients were found to have concurrent pulmonary TB. The most
      consistent laboratory finding (>90%) was a low haemoglobin with a raised C
      reactive protein. The tuberculin test (Mantoux) was positive in only 7 patients
      (22%), and Ziehl-Neelsen staining of ascitic fluid was negative in all 11
      patients in whom it was examined. An ultrasound scan of the abdomen revealed
      findings consistent with TB in 9/28 patients and a CT scan was helpful in 6/11.
      Laparoscopy, although usually performed as a last resort, proved the most
      effective investigation, yielding the diagnosis in 23 (92%) of the 25 patients in
      whom it was performed. In patients with the relevant background and clinical
      history, laparoscopy is the investigation of choice.

PMID- 14645608
TI  - Headache in diabetes--occipital neuropathy.

PMID- 14645609
TI  - Lithium encephalopathy.

PMID- 14645610
TI  - Anticoagulation in a head-injured patient.

PMID- 14645611
TI  - Atypical melanoma.

PMID- 14645612
TI  - Acute haemolytic anaemia after inhalation of amyl nitrite.

PMID- 14645613
TI  - Recurrent axillary vein thrombosis as a manifestation of syringomyelia.

PMID- 14645614
TI  - Undue influence, consent and medical treatment.

PMID- 14645615
TI  - The madness of politics.

PMID- 14645616
TI  - Putrid gums and 'dead men's cloaths': James Lind aboard the Salisbury.
AB  - 18th century sailors often suffered from scurvy. In 1747 James Lind conducted his
      classic experiments aboard the Salisbury, in which he cured scurvy with oranges
      and lemons. The Royal Navy did not introduce citrus rations until 1795. The
      original ship's papers allow the circumstances of the experiment to be
      reconstructed. The relevant patrol began in March 1747, and Lind's experiment
      began after 8 weeks at sea. The muster roll records almost no sickness aboard
      until the ship returned to Plymouth in June. This is at odds with Lind's account
      and suggests an antisickness official culture, which may have contributed to the
      neglect of his work.

PMID- 14645617
TI  - Michelangelo's divine goitre.

PMID- 14645618
TI  - Reducing the toll of road traffic accidents.

PMID- 14645619
TI  - Reducing the toll of road traffic accidents.

PMID- 14645620
TI  - Reducing the toll of road traffic accidents.

PMID- 14645621
TI  - Reducing the toll of road traffic accidents.

PMID- 14645622
TI  - Autonomic dysreflexia.

PMID- 14645623
TI  - Public understanding of science.

PMID- 14645624
TI  - Philoctetes.

PMID- 14645625
TI  - Preputioplasty.

PMID- 14645626
TI  - Philoctetes.

PMID- 14645627
TI  - Chronic viral hepatitis: always be current!

PMID- 14645628
TI  - Index of suspicion.

PMID- 14645629
TI  - Consultation with the specialist: enteral nutrition.

PMID- 14645630
TI  - Visual diagnosis: a 14-year-old male who has fever and rash.

PMID- 14645634
TI  - Therapeutic options for laryngeal cancer.

PMID- 14645635
TI  - Lp(a) lipoprotein--coping with heterogeneity.

PMID- 14645636
TI  - Concurrent chemotherapy and radiotherapy for organ preservation in advanced
      laryngeal cancer.
AB  - BACKGROUND: Induction chemotherapy with cisplatin plus fluorouracil followed by
      radiotherapy is the standard alternative to total laryngectomy for patients with
      locally advanced laryngeal cancer. The value of adding chemotherapy to
      radiotherapy and the optimal timing of chemotherapy are unknown. METHODS: We
      randomly assigned patients with locally advanced cancer of the larynx to one of
      three treatments: induction cisplatin plus fluorouracil followed by radiotherapy,
      radiotherapy with concurrent administration of cisplatin, or radiotherapy alone.
      The primary end point was preservation of the larynx. RESULTS: A total of 547
      patients were randomly assigned to one of the three study groups. The median
      follow-up period was 3.8 years. At two years, the proportion of patients who had
      an intact larynx after radiotherapy with concurrent cisplatin (88 percent)
      differed significantly from the proportions in the groups given induction
      chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone
      (70 percent, P<0.001). The rate of locoregional control was also significantly
      better with radiotherapy and concurrent cisplatin (78 percent, vs. 61 percent
      with induction cisplatin plus fluorouracil followed by radiotherapy and 56
      percent with radiotherapy alone). Both of the chemotherapy-based regimens
      suppressed distant metastases and resulted in better disease-free survival than
      radiotherapy alone. However, overall survival rates were similar in all three
      groups. The rate of high-grade toxic effects was greater with the chemotherapy
      based regimens (81 percent with induction cisplatin plus fluorouracil followed by
      radiotherapy and 82 percent with radiotherapy with concurrent cisplatin, vs. 61
      percent with radiotherapy alone). The mucosal toxicity of concurrent radiotherapy
      and cisplatin was nearly twice as frequent as the mucosal toxicity of the other
      two treatments during radiotherapy. CONCLUSIONS: In patients with laryngeal
      cancer, radiotherapy with concurrent administration of cisplatin is superior to
      induction chemotherapy followed by radiotherapy or radiotherapy alone for
      laryngeal preservation and locoregional control.

PMID- 14645637
TI  - Inhaled nitric oxide in premature infants with the respiratory distress syndrome.
AB  - BACKGROUND: Inhaled nitric oxide improves gas exchange, decreases pulmonary
      vascular lability, and reduces pulmonary inflammation. We hypothesized that the
      use of inhaled nitric oxide would decrease the incidence of chronic lung disease
      and death in premature infants with the respiratory distress syndrome. METHODS:
      We conducted a randomized, double-blind, placebo-controlled study of the effect
      of inhaled nitric oxide during the first week of life on the incidence of chronic
      lung disease and death in premature infants (less than 34 weeks' gestation) who
      were undergoing mechanical ventilation for the respiratory distress syndrome.
      Infants were randomly assigned to receive inhaled nitric oxide (10 ppm on day 1,
      followed by 5 ppm for six days) or inhaled oxygen placebo for seven days. We
      further randomly assigned the infants in each group to receive intermittent
      mandatory or high-frequency oscillatory ventilation. RESULTS: A total of 207
      premature infants were enrolled. In the group given inhaled nitric oxide, 51
      infants (48.6 percent) died or had chronic lung disease, as compared with 65
      infants (63.7 percent) in the placebo group (relative risk, 0.76; 95 percent
      confidence interval, 0.60 to 0.97; P=0.03). There was no significant difference
      between the nitric oxide and placebo groups in the overall incidence of
      intraventricular hemorrhage and periventricular leukomalacia (33.3 percent and
      38.2 percent, respectively), but the group given inhaled nitric oxide had a lower
      incidence of severe intraventricular hemorrhage and periventricular leukomalacia
      (12.4 percent vs. 23.5 percent; relative risk, 0.53; 95 percent confidence
      interval, 0.28 to 0.98; P=0.04). The type of ventilation had no significant
      effect on the outcome. CONCLUSIONS: The use of inhaled nitric oxide in premature
      infants with the respiratory distress syndrome decreases the incidence of chronic
      lung disease and death.

PMID- 14645638
TI  - Lp(a) lipoprotein, vascular disease, and mortality in the elderly.
AB  - BACKGROUND: As compared with what is known about predictors of vascular events in
      middle-aged persons, less is known about these events in the elderly. Lp(a)
      lipoprotein, which plays an important part in atherothrombogenesis, has been
      associated with an increased risk of vascular disease. We investigated this
      relation among older U.S. adults. METHODS: In a prospective study of 5888
      community-dwelling older adults (65 years of age or older) in the United States,
      2375 women and 1597 men who were free of vascular disease provided base-line
      serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects
      were followed for a median of 7.4 years to evaluate the development of stroke and
      to track deaths from vascular causes and all causes. The men and women were
      divided into quintile groups according to the Lp(a) lipoprotein level at base
      line. RESULTS: Using Cox proportional-hazards models, we determined the risk
      associated with each quintile level of Lp(a) lipoprotein, with the lowest
      quintile serving as the reference group. As compared with those in the lowest
      quintile, men in the highest quintile had three times the unadjusted risk of
      stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65),
      almost three times the risk of death associated with vascular events (relative
      risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the
      risk of death from all causes (relative risk, 1.76; 95 percent confidence
      interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total
      cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall
      thickness; smoking status; the presence or absence of diabetes and systolic and
      diastolic hypertension; body-mass index; and other traditional risk factors had
      little effect on the final assessments. Similar analyses for women, which also
      included adjustment for estrogen use or nonuse, revealed no such relation.
      CONCLUSIONS: Among older adults in the United States, an elevated level of Lp(a)
      lipoprotein is an independent predictor of stroke, death from vascular disease,
      and death from any cause in men but not in women. These data support the use of
      Lp(a) lipoprotein levels in predicting the risk of these events in older men.

PMID- 14645639
TI  - Images in clinical medicine. Hypokalemia.

PMID- 14645640
TI  - Surgeon volume and operative mortality in the United States.
AB  - BACKGROUND: Although the relation between hospital volume and surgical mortality
      is well established, for most procedures, the relative importance of the
      experience of the operating surgeon is uncertain. METHODS: Using information from
      the national Medicare claims data base for 1998 through 1999, we examined
      mortality among all 474,108 patients who underwent one of eight cardiovascular
      procedures or cancer resections. Using nested regression models, we examined the
      relations between operative mortality and surgeon volume and hospital volume
      (each in terms of total procedures performed per year), with adjustment for
      characteristics of the patients and other characteristics of the providers.
      RESULTS: Surgeon volume was inversely related to operative mortality for all
      eight procedures (P=0.003 for lung resection, P<0.001 for all other procedures).
      The adjusted odds ratio for operative death (for patients with a low-volume
      surgeon vs. those with a high-volume surgeon) varied widely according to the
      procedure--from 1.24 for lung resection to 3.61 for pancreatic resection. Surgeon
      volume accounted for a large proportion of the apparent effect of the hospital
      volume, to an extent that varied according to the procedure: it accounted for 100
      percent of the effect for aortic-valve replacement, 57 percent for elective
      repair of an abdominal aortic aneurysm, 55 percent for pancreatic resection, 49
      percent for coronary-artery bypass grafting, 46 percent for esophagectomy, 39
      percent for cystectomy, and 24 percent for lung resection. For most procedures,
      the mortality rate was higher among patients of low-volume surgeons than among
      those of high-volume surgeons, regardless of the surgical volume of the hospital
      in which they practiced. CONCLUSIONS: For many procedures, the observed
      associations between hospital volume and operative mortality are largely mediated
      by surgeon volume. Patients can often improve their chances of survival
      substantially, even at high-volume hospitals, by selecting surgeons who perform
      the operations frequently.

PMID- 14645641
TI  - ST-segment elevation in conditions other than acute myocardial infarction.

PMID- 14645642
TI  - Irritable bowel syndrome.

PMID- 14645643
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 37-2003. A 79-year-old man with coronary artery disease,
      peripheral vascular disease, end-stage renal disease, and abdominal pain and
      distention.

PMID- 14645644
TI  - Nitric oxide for preemies--not so fast.

PMID- 14645645
TI  - The volume-outcome conundrum.

PMID- 14645646
TI  - Shedding light on microbial detection.

PMID- 14645647
TI  - Low-intensity versus conventional-intensity warfarin for prevention of recurrent
      venous thromboembolism.

PMID- 14645648
TI  - Coronary angioplasty versus fibrinolytic therapy in acute myocardial infarction.

PMID- 14645649
TI  - Enfuvirtide for prophylaxis against HIV infection.

PMID- 14645650
TI  - Genomic medicine.

PMID- 14645651
TI  - Case 27-2003: a 36-year-old man with recurrent epigastric pain and elevated
      amylase levels.

PMID- 14645652
TI  - A false negative pregnancy test in a patient with a hydatidiform molar pregnancy.

PMID- 14645653
TI  - A large epithelial splenic cyst.

PMID- 14645654
TI  - Images in clinical medicine. Congenital pulmonary lymphangiectasia.

PMID- 14645655
TI  - Constitutive activity and inverse agonists of G protein-coupled receptors: a
      current perspective.
AB  - Over the last decade, the ability to detect agonist-independent signal
      transduction by G protein-coupled receptors has in turn resulted in the detection
      and study of ligands able to block this activity. Such ligands are generically
      described as inverse agonists. Considerable attention has recently been devoted
      to the presence and roles of endogenous antagonist/inverse agonists and the
      concept that inverse agonists may have specific therapeutic benefits compared
      with neutral antagonists.

PMID- 14645656
TI  - Why mice are neither miniature humans nor small rats: a cautionary tale involving
      5-hydroxytryptamine-6 serotonin receptor species variants.

PMID- 14645657
TI  - Loosening the ties that bind--novel strategy to enhance oral bioavailability.

PMID- 14645658
TI  - Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably
      and heterologously expressed in native nicotinic receptor-null SH-EP1 human
      epithelial cells.
AB  - Naturally expressed nicotinic acetylcholine receptors composed of alpha4 and
      beta2 subunits (alpha4beta2-nAChR) are the predominant form of high affinity
      nicotine binding site in the brain implicated in nicotine reward, mediation of
      nicotinic cholinergic transmission, modulation of signaling through other
      chemical messages, and a number of neuropsychiatric disorders. To develop a model
      system for studies of human alpha4beta2-nAChR allowing protein chemical,
      functional, pharmacological, and regulation of expression studies, human alpha4
      and beta2 subunits were stably introduced into the native nAChR-null human
      epithelial cell line SHEP1. Heterologously expressed alpha4beta2-nAChR engage in
      high-affinity, specific binding of 3H-labeled epibatidine (H-EBDN; macroscopic KD
      = 10 pM; kon = 0.74/min/nM, koff = 0.013/min). Immunofluorescence studies show
      alpha4 and beta2 subunit protein expression in virtually every transfected cell,
      and microautoradiographic studies show expression of 125I-labeled iodo
      deschloroepibatidine binding sites in most cells. H-EBDN binding competition
      studies reveal high affinity for nicotinic agonists and lower affinity for
      nicotinic antagonists. Heterologously expressed alpha4beta2-nAChR functional
      studies using 86Rb+ efflux assays indicate full efficacy of epibatidine,
      nicotine, and acetylcholine; partial efficacy for 1,1-dimethyl-4-phenyl
      piperazinium, cytisine, and suberyldicholine; competitive antagonism by dihydro
      beta-erythroidine, decamethonium, and methyllycaconitine; noncompetitive
      antagonism by mecamylamine and eserine; and mixed antagonism by pancuronium,
      hexamethonium, and d-tubocurarine. These results demonstrate utility of
      transfected SH-EP1 cells as models for studies of human alpha4beta2-nAChR, and
      they also reveal complex relationships between apparent affinities of drugs for
      radioligand binding and functional sites on human alpha4beta2-nAChR.

PMID- 14645659
TI  - Differences in the central nervous system distribution and pharmacology of the
      mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors
      investigated by radioligand binding, site-directed mutagenesis, and molecular
      modeling.
AB  - There is increasing evidence for a role of 5-hydroxytrypta-mine-6 (5-HT6)
      receptors in cognitive function. In the rat and human brain, 5-HT6 receptors are
      widely expressed and highly enriched in the basal ganglia. However, in the mouse
      brain, only very low levels of 5-HT6 receptor mRNA and receptor protein, measured
      by TaqMan reverse transcriptase-polymerase chain reaction and selective
      radioligand binding, could be detected, with no evidence of enrichment in the
      basal ganglia. The mouse receptor was cloned and transiently expressed in human
      embryonic kidney 293 cells to characterize its pharmacological profile. Despite
      significant sequence homology between human, rat, and mouse 5-HT6 receptors, the
      pharmacological profile of the mouse receptor was significantly different from
      the rat and human receptors. Four amino acid residues, conserved in rat and human
      and divergent in mouse receptors, were identified, and various mutant receptors
      were generated and their pharmacologies studied. Residues 188 (tyrosine in mouse,
      phenylalanine in rat and human) in transmembrane region 5 and 290 (serine in
      mouse, asparagine in rat and human) in transmembrane region 6 were identified as
      key amino acids responsible for the different pharmacological profiles. Molecular
      modeling of the receptor and docking of selective and nonselective compounds was
      undertaken to elucidate the ligand receptor interactions. The binding pocket was
      predicted to be different in the mouse compared with rat and human 5-HT6
      receptors, and the models were in excellent agreement with the observed mutation
      results and have been used extensively in the design of further selective 5-HT6
      antagonists.

PMID- 14645660
TI  - Altered striatal function and muscarinic cholinergic receptors in
      acetylcholinesterase knockout mice.
AB  - Cholinesterase inhibitors are commonly used to improve cognition and treat
      psychosis and other behavioral symptoms in Alzheimer's disease, Parkinson's
      disease, and other neuropsychiatric conditions. However, mechanisms may exist
      that down-regulate the synaptic response to altered cholinergic transmission,
      thus limiting the efficacy of cholinomimetics in treating disease.
      Acetylcholinesterase knockout (AChE-/-) mice were used to investigate the
      neuronal adaptations to diminished synaptic acetylcholine (ACh) metabolism. The
      striatum of AChE-/- mice showed no changes in choline acetyltransferase activity
      or levels of the vesicular ACh transporter but showed striking 60% increases in
      the levels of the highaffinity choline transporter. This transporter takes
      choline from the synapse into the neuron for resynthesis of ACh. In addition, the
      striata of AChE-/- mice showed dramatic reductions in levels of the M1, M2, and
      M4 muscarinic ACh receptors (mAChRs), but no alterations in dopamine receptors or
      the beta2 subunit of nicotinic receptors. M1, M2, and M4 also showed decreased
      dendritic and cell surface distributions and enhanced intracellular localizations
      in striatal neurons of AChE-/- mice. mAChR antagonist treatment reversed the
      shifts in mAChR distribution, indicating that internalized receptors in AChE-/-
      mice can recover to basal distributions. Finally, AChE-/- mice showed increased
      sensitivity to mAChR antagonist-induced increases in locomotor activity,
      demonstrating functional mAChR down-regulation. mAChR downregulation in AChE-/-
      mice has important implications for the long-term use of cholinesterase
      inhibitors and other cholinomimetics in treating disorders characterized by
      perturbed cholinergic function.

PMID- 14645661
TI  - Functional interactions between mu opioid and alpha 2A-adrenergic receptors.
AB  - Adrenergic and opioid receptors belong to the rhodopsin family of G-protein
      coupled receptors, couple to analogous signal transduction pathways, and affect
      the nociceptive system. Although a number of previous studies have reported
      functional interactions between these two receptors, the basis for this has not
      been well explored. We propose that direct receptor-receptor interactions could
      account, in part, for opioid-adrenergic cross-talk. In this report, we have
      addressed this using biophysical, biochemical, and pharmacological studies. We
      show that mu opioid and alpha2A adrenergic receptors reside in close proximity in
      live cells using the bioluminescence resonance energy transfer assay. These
      receptors colocalize to proximal dendrites in primary hippocampal neurons. mu
      alpha2A Receptor complexes can be isolated from heterologous cells or primary
      neurons coexpressing these receptors. In these cells, the activation of either mu
      or alpha2A receptor leads to a significant increase in the level of
      immunoprecipitable mu-alpha2A complexes, whereas activation of both receptors
      leads to a significant decrease. The implications of these effects on signaling
      were examined using the agonist-mediated increase in G-protein activity and
      mitogen-activated protein kinase activity. We find that activation of either mu
      or alpha2A receptors leads to an increase in the extent of signaling, whereas
      activation of both receptors leads to a decrease. The increase in signaling by
      individual ligands and decrease by a combination of ligands is also seen in
      primary spinal cord neurons endogenously expressing these receptors. Taken
      together, these results suggest that physical associations between mu and alpha2A
      receptors could play a role in the functional interactions between these
      receptors.

PMID- 14645662
TI  - Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n
      propylsulfanilamide (GB-II-5) against kinetoplastid parasites.
AB  - Analogs of the antimitotic herbicide oryzalin (3,5-dinitro-N4,N4-di-n
      propylsulfanilamide) were recently prepared that were more potent in vitro than
      the parent compound against the kinetoplastid parasite Leishmania donovani
      (Bioorg Med Chem Lett 12:2395-2398, 2002). In the present work, we show that the
      most active molecule in the group, N1-phenyl-3,5-dinitro-N4,N4-di-n
      propylsulfanilamide (GB-II-5), is a potent, selective antimitotic agent against
      kinetoplastid parasites. GB-II-5 possesses IC50 values of 0.41 and 0.73 microM in
      vitro against two strains of the related parasite Trypanosoma brucei but is much
      less toxic to J774 murine macrophages and PC3 prostate cancer cells, exhibiting
      IC50 values of 29 and 35 microM against these lines, respectively. Selectivity is
      also observed for GB-II-5 with purified leishmanial and mammalian tubulin. The
      assembly of 15 microM leishmanial tubulin is completely inhibited by 10 microM GB
      II-5, whereas 40 microM GB-II-5 inhibits the assembly of 15 microM porcine brain
      tubulin by only 17%. In cultured L. donovani and T. brucei, treatment with 5 and
      0.5 microM GB-II-5, respectively, causes a striking increase in the fraction of
      G2M cells compared with control. Given the potency and selectivity of this agent
      against kinetoplastid tubulin, GB-II-5 emerges as an exciting new
      antitrypanosomal and antileishmanial lead compound.

PMID- 14645663
TI  - A novel synthetic cannabinoid derivative inhibits inflammatory liver damage via
      negative cytokine regulation.
AB  - The therapeutic potential of cannabinoids has been described previously for
      several inflammatory diseases, but the molecular mechanisms underlying the anti
      inflammatory properties of cannabinoids are not well understood. In this study,
      we investigated the mechanism of action of a novel synthetic cannabinoid,
      [(+)(6aS,10aS)-6,6-Dimethyl-3-(1,1-dimethylheptyl)-1-hydroxy-9-(1H-imidazol-2
      ylsulfanylmethyl]-6a,7,10,10a-tetrahydro-6H-dibenzo[b,d]pyran (PRS-211,092) that
      has no psychotropic effects but exhibits immunomodulatory properties. Treatment
      with PRS-211,092 significantly decreased Concanavalin A-induced liver injury in
      mice that was accompanied by: 1) promotion of early gene expression of
      interleukin (IL)-6 and IL-10 that play a protective role in this model; 2)
      induction of early gene expression of the suppressors of cytokine signaling (SOCS
      1 and 3), followed by 3) inhibition of several pro-inflammatory mediators,
      including IL-2, monocyte chemoattractant protein-1 (MCP-1), IL-1beta, interferon
      gamma, and tumor necrosis factor alpha. Based on these results, we propose a
      mechanism by which PRS-211,092 stimulates the expression of IL-6, IL-10 and the
      SOCS proteins that, in turn, negatively regulates the expression of pro
      inflammatory cytokines. Negative regulation by PRS-211,092 was further
      demonstrated in cultured T cells, where it inhibited IL-2 production and nuclear
      factor of activated T cells activity. These findings suggest that this
      cannabinoid derivative is an immunomodulator that could be developed as a
      potential drug for hepatitis as well as for other short- or long-term
      inflammatory diseases.

PMID- 14645664
TI  - Ligand structure-activity requirements and phospholipid dependence for the
      binding of phorbol esters to protein kinase D.
AB  - Although protein kinase D (PKD), like protein kinase C (PKC), possesses a C1
      domain that binds phorbol esters and diacylglycerol, the structural differences
      from PKC within this and other domains of PKD imply differential regulation by
      lipids and ligands. We characterized the phorbol ester and phospholipid binding
      properties of a glutathione S-transferase-tagged full-length PKD and compared
      them with those of PKC-alpha and -delta. We found that PKD is a high-affinity
      phorbol ester receptor for a range of structurally and functionally divergent
      phorbol esters and analogs and showed both similarities and differences in
      structure-activity relations compared with the PKCs examined. In particular, PKD
      had lower affinity than PKC for certain diacylglycerol analogs, which might be
      caused by a lysine residue at the 22 position of the PKD-C1b domain in place of
      the tryptophan residue at this position conserved in the PKCs. The membrane
      targeting domains in PKD are largely different from those in PKC; among these
      differences, PKD contains a pleckstrin homology (PH) domain that is absent in
      PKC. However, phosphatidylinositol-4,5-bisphosphate PIP2, a lipid ligand for some
      PH domains, reconstitutes phorbol 12,13-dibutyrate (PDBu) binding to PKD
      similarly as it does to PKC-alpha and -delta, implying that the PH domain in PKD
      may not preferentially interact with PIP2. Overall, the requirement of anionic
      phospholipids for the reconstitution of [3H]PDBu binding to PKD was intermediate
      between those of PKC-alpha and -delta. We conclude that PKD is a high-affinity
      phorbol ester receptor; its lipid requirements for ligand binding are
      approximately comparable with those of PKC but may be differentially regulated in
      cells through the binding of diacylglycerol to the C1 domain.

PMID- 14645665
TI  - A new and simple method for delivering clamped nitric oxide concentrations in the
      physiological range: application to activation of guanylyl cyclase-coupled nitric
      oxide receptors.
AB  - The signaling molecule nitric oxide (NO) could engage multiple pathways to
      influence cellular function. Unraveling their relative biological importance has
      been difficult because it has not been possible to administer NO under the steady
      state conditions that are normally axiomatic for analyzing ligand-receptor
      interactions and downstream signal transduction. To address this problem, we
      devised a chemical method for generating constant NO concentrations, derived from
      balancing NO release from a NONOate donor with NO consumption by a sink. On
      theoretical grounds, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3
      oxide (CPTIO) was selected as the sink. The mixture additionally contained urate
      to convert an unwanted product of the reaction (NO2) into nitrite ions. The
      method enabled NO concentrations covering the physiological range (0-100 nM) to
      be formed within approximately 1 s. Moreover, the concentrations were
      sufficiently stable over at least several minutes to be useful for biological
      purposes. When applied to the activation of guanylyl cyclase-coupled NO
      receptors, the method gave an EC50 of 1.7 nM NO for the protein purified from
      bovine lung, which is lower than estimated previously using a biological NO sink
      (red blood cells). The corresponding values for the alpha1beta1 and alpha2beta1
      isoforms were 0.9 nM and 0.5 nM, respectively. The slopes of the concentration
      response curves were more shallow than before (Hill coefficient of 1 rather than
      2), questioning the need to consider the binding of more than one NO molecule for
      receptor activation. The discrepancies are ascribable to limitations of the
      earlier method. Other biological problems can readily be addressed by adaptations
      of the new method.

PMID- 14645666
TI  - Agonist and inverse agonist actions of beta-blockers at the human beta 2
      adrenoceptor provide evidence for agonist-directed signaling.
AB  - Beta-blockers have beneficial effects in heart failure, although the underlying
      mechanism is unknown. Beta2-adrenoceptors, however, are proportionally higher in
      the failing human heart. This study shows several clinically used beta-blockers
      are agonists at the human beta2-adrenoceptor. Although these agonist effects were
      small at the cAMP level, they were substantial at the level of cAMP response
      element (CRE)-mediated gene transcription. Some of the effects of "beta-blockers"
      seen in heart failure may be related to the beta2-agonist actions of these
      compounds. CRE-gene transcription responses to beta2-agonists, forskolin, and
      cAMP-analogs were sensitive to p42/44-mitogen-activated protein (MAP) kinase
      pathway inhibitors. p42/44-MAP kinase activation was also shown directly by
      western blotting and enzyme-linked immunosorbent assay techniques. N-[2-(4
      bromocinnamylamino)ethyl]-5-isoquinoline (H89; a protein kinase A inhibitor)
      stimulated cAMP accumulation and CRE gene transcription via the beta2
      adrenoceptor at concentrations at which protein kinase A was inhibited, providing
      evidence for an alternative pathway. Propranolol, however, produced paradoxical
      effects; it reduced basal cAMP accumulation (via beta2-mediated inverse agonism)
      but stimulated beta2-mediated CRE gene transcription. This cannot be explained by
      a sequential pathway from Gs-adenylyl cyclase-cAMP to CRE binding protein
      phosphorylation. Both responses to propranolol were insensitive to pertussis
      toxin, thus excluding Gi-protein involvement. Propranolol CRE gene transcription
      responses were attenuated by p42/44-MAP kinase inhibitors and propranolol was
      also found to directly stimulate the p42/44-MAP kinase pathway. Studies of
      inositol phosphate accumulation and of protein kinase C or Rho kinase inhibitors
      on CRE-gene transcription provided no evidence for Gq/11 or G12/13 involvement.
      These data suggest that propranolol can simultaneously act as an inverse agonist
      through a Gs-coupled mechanism while stimulating the p42/44-MAP kinase pathway
      through an alternative G-protein-independent mechanism.

PMID- 14645667
TI  - Growth and DNA damage-inducible transcription factor 153 mediates apoptosis in
      response to fenretinide but not synergy between fenretinide and chemotherapeutic
      drugs in neuroblastoma.
AB  - Fenretinide induces apoptosis of neuroblastoma cells in vitro and interacts
      synergistically with the chemotherapeutic drugs cisplatin and etoposide. The
      stress-inducible transcription factor known as growth and DNA damage (GADD)
      inducible transcription factor 153 is induced in response to fenretinide and in
      other cell types modulates apoptosis via pro- and antiapoptotic members of the
      BCL2 family. Because BCL2-family proteins are important in apoptosis induced by
      chemotherapeutic drugs, GADD153 may be a key mediator of synergy between
      fenretinide and chemotherapeutic drugs. To investigate this, GADD153 cDNA in
      sense and antisense orientations was stably transfected into SH-SY5Y
      neuroblastoma cells using a tetracycline-inducible vector. Increased expression
      of GADD153 raised the background level of apoptosis and increased apoptosis
      induced by fenretinide or the chemotherapeutic drugs cisplatin and etoposide.
      However, there was no increase in synergy between fenretinide and
      chemotherapeutic drugs. Conversely, expression of antisense-GADD153 virtually
      abolished the induction of apoptosis in response to fenretinide but overall had
      no significant effect on apoptosis induced by chemotherapeutic drugs. The effect
      of antisense-GADD153 on synergy between chemotherapeutic drugs and fenretinide
      varied with the drug used: there was no effect on synergy between fenretinide and
      cisplatin, but the combination of fenretinide with etoposide became antagonistic.
      These results suggest that mechanisms mediating synergy between fenretinide and
      chemotherapeutic drugs lie upstream of GADD153.

PMID- 14645668
TI  - Subtype-specific dimerization of alpha 1-adrenoceptors: effects on receptor
      expression and pharmacological properties.
AB  - The potential role of dimerization in controlling the expression and
      pharmacological properties of alpha1-adrenoceptor subtypes was examined using
      coimmunoprecipitation of epitope-tagged receptors. Human alpha1-adrenoceptor
      subtypes (alpha1A, alpha1B, alpha1D) were tagged at their amino-termini with Flag
      or hemagglutinin epitopes and transfected into human embryonic kidney 293 cells.
      Homodimerization of all three subtypes was observed by coimmunoprecipitation of
      receptors with different tags and was not altered by norepinephrine treatment.
      Heterodimer formation between hemagglutinin-tagged alpha1B-adrenoceptors and Flag
      tagged alpha1A- or alpha1D-adrenoceptors was also observed. However, no
      alpha1A/alpha1D-adrenoceptor heterodimers were observed, suggesting that
      dimerization is subtype-specific. The extent of heterodimerization was also
      unaltered by norepinephrine treatment. alpha1-Adrenoceptor truncation mutants
      lacking carboxyl or amino-terminal sequences formed homo- and heterodimers
      similarly to full-length receptors, suggesting that these domains play little or
      no role in dimerization. Biotinylation with a membrane-impermeable agent showed
      that monomers and homo- and hetero-oligomers of all three subtypes are expressed
      on the cell surface. Radioligand binding studies showed that heterodimerization
      did not alter the affinity of alpha1-adrenoceptors for norepinephrine, prazosin,
      or subtype-selective antagonists, suggesting that dimerization does not result in
      pharmacologically distinct subtypes. However, coexpression of alpha1B
      adrenoceptors significantly increased both binding site density and protein
      expression of alpha1A- and alpha1D-adrenoceptors, and increased cell surface
      expression of alpha1D-adrenoceptors, suggesting a functional role for
      heterodimerization. Conversely, coexpression of alpha1A-with alpha1D
      adrenoceptors, which did not heterodimerize, had no effect on receptor density or
      protein. These studies demonstrate subtype-selective heterodimerization of alpha1
      adrenoceptors, which does not change their pharmacological properties but seems
      to have functional consequences in regulating receptor expression and
      trafficking.

PMID- 14645669
TI  - Mu opioid transactivation and down-regulation of the epidermal growth factor
      receptor in astrocytes: implications for mitogen-activated protein kinase
      signaling.
AB  - Astroglia are a principal target of long-term mu antiproliferative actions. The
      mitogen-activated protein (MAP) kinase known as extracellular signal-regulated
      kinase (ERK), is a key mediator of cell proliferation. In studies on the
      mechanism of short- and long-term mu opioid regulation of the ERK signaling
      pathway, we show that the mu opioid agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin
      (DAMGO), acting via the endogenous mu opioid receptor (MOR), induced sequential
      epidermal growth factor receptor (EGF) receptor (EGFR) Tyr phosphorylation, Ser
      phosphorylation, and down-regulation in immortalized rat cortical astrocytes. The
      short-term action of DAMGO resulted in the stimulation of ERK phosphorylation.
      4(3-Chlorophenylamino)-6,7-dimethoxyquinazoline (Tyrphostin AG1478), a selective
      inhibitor of EGFR Tyr kinase activity, blocked EGFR and ERK activation by short
      term DAMGO administration, implicating EGFR transactivation in its stimulation of
      ERK activity. Inhibitors of matrix metalloproteinases attenuated MOR-mediated ERK
      phosphorylation, suggesting that shedding of EGF-like ligands from the plasma
      membrane may be involved in the EGFR transactivation process. Prolonged DAMGO
      exposure induced EGFR internalization/down-regulation, did not activate ERK, and
      inhibited exogenous EGF-stimulated ERK phosphorylation. MOR-mediated EGFR down
      regulation seems to be MAP kinase-dependent, because it was inhibited by the ERK
      kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio) butadiene
      (U0126), and tyrphostin AG1478. The kappa opioid agonist (5alpha,7alpha,8beta)-(
      )-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl) benzeneacetamide
      (U69,593) induced Tyr and Ser phosphorylation of EGFR and activation of ERK.
      However, long-term application of U69,593 neither down-regulated EGFR nor
      inhibited EGF-induced ERK activation. Instead, it engendered a sustained
      activation of ERK. Collectively, our data suggest that long-term application of
      DAMGO initiates heterologous down-regulation of EGFR via a mechanism involving
      ERK in astrocytes.

PMID- 14645670
TI  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes
      mitochondrial dysfunction and apoptosis induced by 7-hydroxystaurosporine and
      mitogen-activated protein kinase kinase inhibitors in human leukemia cells that
      ectopically express Bcl-2 and Bcl-xL.
AB  - Previous studies have demonstrated that cotreatment with mitogen activated
      protein kinase kinase (MEK) 1/2 inhibitors (e.g., PD184352) and the checkpoint
      abrogator 7-hydroxystaurosporine (UCN-01) dramatically induces apoptosis in a
      variety of human leukemia and multiple myeloma cell types. The purpose of this
      study was to evaluate the roles of Bcl-2 family members and the relative
      contribution of the intrinsic mitochondrial versus the extrinsic receptor-related
      apoptotic pathways to MEK inhibitors/UCN-01-induced leukemic cell death.
      Cotreatment of U937 cells with PD184352 and UCN-01 resulted in the activation of
      procaspase-3, -9, and -8 as well as Bid cleavage. PD184352/UCN-01-induced
      mitochondrial dysfunction and apoptosis were both substantially attenuated in
      cells ectopically expressing Bcl-2, an N-terminal phosphorylation loop-deleted
      mutant Bcl-2, or Bcl-xL, but not in cells expressing dominant-negative (DN)
      caspase-8, cytokine response modifier A (cowpox virus-encoded antiapoptotic
      protein), or DN Fas-associated death domain. Coadministration of tumor necrosis
      factor (TNF)-related apoptosis-inducing ligand (TRAIL) or TNF-alpha substantially
      increased MEK inhibitors (e.g., PD184352 or U0126)/UCN-01-induced mitochondrial
      dysfunction, activation of procaspase-8 and Bid, and apoptosis in Bcl-2- and Bcl
      xL-overexpressing cells but not in those in which the extrinsic pathway was
      interrupted. Together, these findings suggest that the MEK inhibitors/UCN-01
      regimen primarily induces leukemic cell apoptosis by engaging the intrinsic,
      mitochondrial apoptotic pathway and that resistance to these events conferred by
      increased expression of certain antiapoptotic Bcl-2 family members can be
      overcome, at least in part, by coadministration of TRAIL and other agents that
      activate the extrinsic apoptotic cascade.

PMID- 14645671
TI  - Transcriptional regulation of mu opioid receptor gene by cAMP pathway.
AB  - The utility of morphine for the treatment of chronic pain is hindered by the
      development of tolerance. Fentanyl has been shown to be a potent analgesic with a
      lower propensity to produce tolerance and physical dependence in the clinical
      setting. Previous finding has shown that fentanyl induces mu opioid receptor gene
      expression in PC-12 cells (Brain Res 859:217-223, 2000). In this report, we aim
      to identify the molecular mechanism of mu-opioid receptor (MOR) gene regulation
      by fentanyl. We demonstrated that the 4.7-kilobase MOR promoter could be induced
      by fentanyl in PC-12 cells, and we defined a partial cAMP response element (CRE)
      located at -106/-111 in 5'-untranslated region of the MOR gene. In
      electrophoretic mobility shift assay, cAMP response element-binding protein
      (CREB) was found in the protein-DNA complex formed on the CRE box. CREB was
      phosphorylated after forskolin induction, and both CREB and CREB-binding protein
      (CBP) binding to the endogenous MOR promoter was increased by forskolin in
      chromatin immunoprecipitation assay. The functional role of CREB in the induction
      of MOR gene was further elucidated by an experiment in which a dominant-negative
      mutant CREB, CREB-S133A, abolished the forskolin-mediated MOR induction.
      Moreover, we found that this CRE box is conserved in mouse, rat, and human MOR
      gene, implying physiological relevance in different species. Collectively, this
      study demonstrated that fentanyl-triggered MOR gene induction was mediated by the
      sequential activation of CREB and the binding of CREB and CBP to MOR promoter,
      thus provides direct evidence for lower propensity of fentanyl to produce
      tolerance.

PMID- 14645672
TI  - Soluble guanylyl cyclase activator YC-1 inhibits human neutrophil functions
      through a cGMP-independent but cAMP-dependent pathway.
AB  - 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a novel type of soluble
      guanylyl cyclase (sGC) activator, is useful in investigating the signaling of
      cGMP and may provide a new approach for treating cardiovascular diseases. Herein,
      YC-1 was demonstrated to inhibit the generation of superoxide anion (O2-) and the
      release of beta-glucuronidase release, to diminish the membrane-associated
      p47phox and to accelerate resequestration of cytosolic calcium in formyl-l
      methionyl-l-leucyl-l-phenylalanine-activated human neutrophils. YC-1 not only
      directly promoted sGC activity and cGMP formation but also dramatically
      potentiated sodium nitroprusside-induced sGC activity and cGMP formation in human
      neutrophils. However, the synergistic increase in the amount of cGMP was
      inconsistent with its cellular response. Moreover, neither an sGC inhibitor nor
      protein kinase G inhibitors reversed the inhibitory effect of YC-1.
      Interestingly, YC-1 also increased the cAMP concentration and protein kinase
      (PK)A activity. The inhibitory effect of YC-1 was significantly enhanced by
      prostaglandin (PG)E1 and isoproterenol, and almost abolished by PKA inhibitors.
      These results show that cAMP, but not cGMP, mediates the YC-1-induced inhibition
      of human neutrophils. YC-1 increased the PGE1- and forskolin-induced but not 3
      isobutyl-1-methylxanthine-produced cAMP formation, suggesting inhibition of
      phosphodiesterase. These findings thus reveal novel mechanism-mediated anti
      inflammatory properties of YC-1 in human neutrophils, which can influence the
      progression of cardiovascular disease. cAMP, but not cGMP, plays an important
      role in the regulation of respiratory burst and degranulation in human
      neutrophils.

PMID- 14645673
TI  - Estren is a selective estrogen receptor modulator with transcriptional activity.
AB  - It was recently reported that the synthetic compound estren increases bone mass
      without affecting reproductive organs or classic transcription. The aim of the
      present study was to further characterize the in vivo and in vitro effects of
      estren. We demonstrate that estren is a selective estrogen receptor modulator
      (SERM) with a strong effect on thymus, a moderate effect on uterus and trabecular
      bone, but no major effect on fat or cortical bone in 11-month-old ovariectomized
      mice. The effect of estren on trabecular bone and uterus is mediated via estrogen
      receptors (ERs) because no effect is seen in ER double-inactivated mice.
      Furthermore, with the use of ERalpha- and ERbeta-expressing reporter cell lines,
      we demonstrate that estren displays an agonistic effect on transcriptional
      activity of an estrogen-responsive element-driven reporter gene with a degree of
      agonism similar to that of 17beta-estradiol for both ERalpha and ERbeta. Thus,
      estren has the capacity to exert genomic effects via both ERalpha and ERbeta. We
      conclude, in contrast to what was previously reported by others, that estren is a
      SERM with transcriptional activity.

PMID- 14645674
TI  - Heterogeneous role of caspase-8 in fenretinide-induced apoptosis in epithelial
      ovarian carcinoma cell lines.
AB  - The mechanism of action of fenretinide, a synthetic retinoid currently undergoing
      testing as a chemopreventive and chemotherapeutic agent, is incompletely
      understood. In the present study, fenretinide caused apoptotic changes, including
      DNA fragmentation and cleavage of caspase substrates, in six low-passage ovarian
      cancer cell lines. However, the caspase activation pathway used by this agent
      varied. Transient transfection of cDNA-encoding cytokine response modifier A
      (CrmA), a caspase-8 inhibitor, diminished fenretinide-induced death in OV177
      cells. Likewise, IETD(OMe)-fluoromethylketone (fmk) inhibited fenretinide-induced
      apoptosis by >80% in OV177 or OV266 cells and by approximately 50% in OV17,
      OV167, or OV207 cells. Further analysis demonstrated that inhibition of Fas
      ligand, tumor necrosis factor-alpha, or TRAIL signaling with blocking reagents
      did not affect fenretinide-induced apoptosis, raising the possibility that
      fenretinide activates caspase-8 in a death receptor-independent manner. In
      contrast, CrmA transfection or IETD(OMe)-fmk treatment did not inhibit
      fenretinide-induced apoptosis in OV202 cells. These divergent behaviors did not
      correlate with increased levels of procaspase-10, which is relatively resistant
      to CrmA and IETD(OMe)-fmk, nor with the expression of procaspase-8 and -9,
      apoptotic protease activating factor-1, or cellular FLICE-like inhibitory
      protein. Similarly, fenretinide treatment increased ceramide levels equally in
      cells that do (OV177) and do not (OV202) rely on caspase-8 to initiate apoptosis.
      These results indicate that synthetic retinoids can use caspase-8 as an
      initiating caspase, but they also indicate unexpected heterogeneity in caspase
      activation pathways among closely related cell lines.

PMID- 14645675
TI  - Role of muscarinic receptor subtypes in the constriction of peripheral airways:
      studies on receptor-deficient mice.
AB  - In the airways, increases in cholinergic nerve activity and cholinergic
      hypersensitivity are associated with chronic obstructive pulmonary disease and
      asthma. However, the contribution of individual muscarinic acetylcholine receptor
      subtypes to the constriction of smaller intrapulmonary airways that are primarily
      responsible for airway resistance has not been analyzed. To address this issue,
      we used videomicroscopy and digital imaging of precision-cut lung slices derived
      from wild-type mice and mice deficient in either the M1 (mAChR1-/- mice), M2
      (mAChR2-/- mice), or M3 receptor subtype (mAChR3-/- mice) or lacking both the M2
      and M3 receptor subtypes (mAChR2/3-/- double-knockout mice). In peripheral
      airways from wild-type mice (mAChR+/+ mice), muscarine induced a triphasic
      concentration-dependent response, characterized by an initial constriction, a
      transient relaxation, and a sustained constriction. The bronchoconstriction was
      diminished by up to 60% in mAChR3-/- lungs and was completely abolished in
      mAChR2/3-/- lungs. The sustained bronchoconstriction was reduced in mAChR2-/-
      bronchi, and, interestingly, the transient relaxation was absent; the
      bronchoconstriction in response to 10-8 M muscarine was increased by 158% in
      mAChR1-/- mice. Quantitative reverse transcriptase-polymerase chain reaction
      analysis revealed that the disruption of specific mAChR genes had no significant
      effect on the expression levels of the remaining mAChR subtypes. These results
      demonstrate that cholinergic constriction of murine peripheral airways is
      mediated by the concerted action of the M2 and M3 receptor subtypes and suggest
      the existence of pulmonary M1 receptor activation, which counteracts cholinergic
      bronchoconstriction. Given the important role of muscarinic cholinergic
      mechanisms in pulmonary disease, these findings should be of considerable
      therapeutic relevance.

PMID- 14645676
TI  - Functional characterization of human breast cancer resistance protein (BCRP,
      ABCG2) expressed in the oocytes of Xenopus laevis.
AB  - To evaluate the function and substrate specificity of human breast cancer
      resistance protein (BCRP, ABCG2) in the absence of cofactors or heterologous
      partner proteins, Xenopus laevis oocytes were injected with cRNA of wild-type or
      mutant (R482T) BCRP. High expression of BCRP was observed on the oocyte surface.
      Accumulation and efflux assays revealed that oocytes expressing R482T transported
      daunorubicin (DNR), mitoxantrone (MX), rhodamine 123, and flavopiridol (FLV),
      whereas wild-type BCRP transported only MX and FLV, in agreement with
      observations in mammalian and other systems. Transport activity was completely
      inhibited by fumitremorgin C, a known inhibitor of BCRP. Injection of oocytes
      with cRNA containing mutations of serine 187 in the ATP-binding cassette
      signature motif (S187T or S187A) resulted in strong expression of the mutant
      forms; however, these oocytes were devoid of transporter activity. When oocytes
      were coinjected with R482T and R482T/S187T, DNR transport was inhibited in a
      manner dependent on the amount of R482T/S187T cRNA added, consistent with the
      idea that the active form of BCRP is a homodimer or homomultimer. Substrate
      interaction studies found that no two substrates reciprocally inhibited the
      efflux of the other. Although FLV proved to be an effective inhibitor of both MX
      and DNR transport, and MX inhibited DNR transport, the other substrates tested
      had only weak or no inhibitory activity, indicating a complex nature of substrate
      interaction with the BCRP homodimer. We conclude that the X. laevis oocyte
      heterologous expression system is a valid and effective means of studying BCRP
      function and substrate specificity.

PMID- 14645677
TI  - Caffeine regulates neuronal expression of the dopamine 2 receptor gene.
AB  - The psychoactive drug caffeine influences neuronal physiology; however, it is
      unknown whether it can dynamically alter the expression of genes that influence
      neurotransmission. Here, we report that caffeine stimulates transcription of the
      dopamine 2 receptor (D2R) gene in PC-12 cells and primary striatal cultures and
      increases D2R protein expression in the striatum. Physiological doses of caffeine
      and the specific adenosine 2A receptor antagonist 8-(3-chlorostyryl) caffeine
      both increased the activity of a D2R/luciferase reporter construct within 24 h,
      and simultaneous treatment with 2-[p-(2-carboxyethyl)phenethylamino]-5'-N
      ethylcarboxamidoadenosine (CGS 21680), a specific adenosine 2A receptor agonist,
      eliminated this effect. Tests of additional constructs revealed that specific
      regions of the D2R promoter (-117/-75) and 5'-untranslated region (+22/+317) were
      required for activation of D2R gene expression by caffeine. In primary striatal
      cultures, caffeine increased spontaneous firing of neurons between 12 and 80 min
      after treatment, whereas it increased D2R mRNA expression after only 4 h. These
      results indicate that regulation of D2R gene expression by caffeine occurs after
      the initial physiological response has subsided. In vivo, female mice treated
      with a dose of caffeine (50 mg/kg) showed 1.94- and 2.07-fold increases in D2R
      mRNA and protein expression, respectively. In contrast, male mice exhibited a 31%
      decrease in D2R mRNA expression and showed no changes in D2R protein expression.
      Collectively, these results demonstrate for the first time that caffeine alters
      D2R expression in neurons. They also suggest that caffeine consumption can lead
      to sexually dimorphic patterns of gene expression in the brain.

PMID- 14645678
TI  - Ligand specific up-regulation of a Renilla reniformis luciferase-tagged,
      structurally unstable muscarinic M3 chimeric G protein-coupled receptor.
AB  - The rat muscarinic acetylcholine receptor subtype 3 was modified by swapping the
      third intracellular loop with the corresponding region of a constitutively active
      mutant human beta2-adrenergic receptor and attaching Renilla reniformis
      luciferase to its C terminus. The chimeric fusion receptor displayed constitutive
      Gq- and Gs-coupled activity as demonstrated in nuclear factor of activated T cell
      and cAMP response element reporter gene assays. The chimeric receptor displayed a
      pharmacological binding profile comparable with that of the wild-type receptor
      for agonists, antagonists, and inverse agonists but showed a large decrease in
      expression in both human embryonic kidney 293 and COS-7 cells. Long-term
      treatment of cells expressing the chimeric receptor with agonists, antagonists,
      and inverse agonists resulted in a concentration-dependent up-regulation in the
      steady-state levels that was not observed for the wild-type receptor. The EC50 of
      neutral antagonists and inverse agonists was significantly correlated to their
      binding affinities at the wild-type receptor, whereas agonists demonstrated
      greater EC50 values for the chimeric receptor. To validate the approach as a
      means of discovering novel receptor modulators, a cell-based, high-throughput
      screening assay was developed and used to screen a small molecule compound
      collection against the chimeric fusion receptor. Several novel hits were
      identified and confirmed by ligand binding assay and functional assays using the
      wild-type rat muscarinic acetylcholine receptor subtype 3.

PMID- 14645679
TI  - Hypoxia inducible factor-1 alpha-independent suppression of aryl hydrocarbon
      receptor-regulated genes by nickel.
AB  - Aryl hydrocarbon receptor (AhR)-dependent enzymes are involved in the
      biotransformation of harmful xenobiotics into more easily excretable metabolites.
      Cross-talk between the AhR pathway and the hypoxia inducible factor-1alpha (HIF
      1alpha) pathway has been demonstrated previously, although the mechanism remains
      unclear and quite controversial. Because nickel is known to mimic hypoxia, we
      investigated the effects of short-term nickel exposure on AhR-dependent gene
      expression. Gene-chip analysis identified several AhR-dependent genes that are
      suppressed by exposure to nickel. Using Northern blots, we then confirmed that
      nickel can down-regulate both the basal and benzo[a]pyrene-inducible expression
      of AhR-dependent genes in mouse and human cell lines. Using a HIF-1alpha knockout
      cell line and 3-[2-[4-(bis-(4-fluorophenyl) methylene]-1-piperidinyl)ethyl]-2,3
      dihydro-2-thioxo-4(1H)quinazolinone (R59949), which blocks HIF-1alpha protein
      accumulation, we show HIF-1alpha-independent suppression of AhR-dependent genes
      by nickel. Desferrioxamine and hypoxia were also able to suppress the basal and
      inducible expression levels of AhR-regulated genes. Finally,
      dimethyloxalylglycine, an inhibitor of Fe(II)- and 2-oxoglutarate-dependent
      dioxygenases also inhibited AhR-dependent expression in a HIF-1alpha-independent
      manner. Our data suggest that an Fe(II)-, oxoglutarate-, and oxygen-dependent
      enzyme may directly or indirectly be involved in the regulation of AhR-dependent
      transcriptional activity by nickel and other hypoxia-mimicking agents.

PMID- 14645680
TI  - Nitric oxide levels in human preneoplastic colonocytes determine their
      susceptibility toward antineoplastic agents.
AB  - The efficacy of antineoplastic compounds can depend heavily on the genetic
      background of the cells exposed to the drugs. This becomes evident by the fact
      that HT-29 human colon cancer cells but not primary murine nontransformed
      colonocytes are efficiently submitted to apoptosis by the flavonoid flavone. By
      determining caspase-3 activation, plasma membrane disintegration, and nuclear
      fragmentation, we show here that flavone also does not promote apoptosis in
      preneoplastic NCOL-1 colonocytes derived from a nontransformed human biopsy
      specimen. In clear contrast, the antitumor drug camptothecin potently induces
      apoptosis in NCOL-1 cells associated with a specific down-regulation of the
      antiapoptotic factor bcl-XL at the mRNA and protein levels and with the
      activation of the mitochondrial apoptosis pathway. Confocal microscopy revealed
      an increased production of superoxide anion radicals in the mitochondria of NCOL
      1 cells that preceded the apoptotic events. However, in the case of flavone, the
      mitochondrial oxygen radicals were effectively scavenged by physiological
      concentrations of nitric oxide (NO), whereas in the case of camptothecin, the
      available nitric oxide was rapidly scavenged by the production of large
      quantities of cytosolic superoxide anions. Increasing the levels of nitric oxide
      inside NCOL-1 cells by sodium nitroprusside prevented the apoptosis induction by
      camptothecin. Reducing the levels of nitric oxide by using the NO synthase
      inhibitor, Nomega-nitro-l-arginine methyl ester in NCOL-1 cells or using HT-29
      cells that intrinsically have low NO levels enabled flavone to trigger the
      apoptosis pathway. In conclusion, our studies demonstrate that the intracellular
      levels of nitric oxide significantly change the apoptotic response to
      antineoplastic agents in colonic cells.

PMID- 14645681
TI  - A calcium-initiated signaling pathway propagated through calcineurin and cAMP
      response element-binding protein activates proenkephalin gene transcription after
      depolarization.
AB  - Essential components of a signal-transduction pathway regulating activity
      dependent neuropeptide gene transcription have been identified. Proenkephalin
      (PEnk) gene activation after depolarization of chromaffin cells with 40 mM KCl
      was blocked by the voltage-sensitive calcium-channel blocker methoxyverapamil
      (D600) (30 microM) and by calcineurin inhibition with 100 nM cyclosporin A or
      ascomycin but not by inhibiting new protein synthesis with 0.5 microg/ml
      cycloheximide. KCl-induced elevation of PEnk mRNA was distinct from activation of
      the PEnk gene by either cAMP or protein kinase C. Twenty-five micromolar
      forskolin- and 100 nM phorbol 12-myristate 13-acetate-induced elevations of PEnk
      mRNA were cycloheximide-sensitive and were not blocked by cyclosporin A or
      ascomycin. KCl stimulated Ser-133 phosphorylation of cAMP response element
      binding protein (CREB) in chromaffin cells, and CREB phosphorylation was blocked
      by both ascomycin and D600. A reporter gene containing 193 bases of the PEnk gene
      5' flank driving luciferase gene expression (pENK12-Luc) transfected into
      chromaffin cells was transcriptionally activated by KCl depolarization.
      Activation was blocked by both ascomycin and D600 and required an intact CREB
      binding site (ENKCRE2). An oligonucleotide containing the PEnk cAMP response
      element-2 was gel-shifted by both unstimulated and potassium-stimulated
      chromaffin cell nuclear extracts into a prominent complex supershifted by CREB
      antibodies. Finally, stimulation of transcription of the pENK12-Luc reporter by
      KCl in chromaffin cells was blocked by coexpression of the CREB antagonist A-CREB
      but not by the AP-1 antagonist A-Fos. Stimulus-transcription coupling after
      depolarization in chromaffin cells occurs via calcineurin-dependent activation of
      CREB, a pathway distinct from cAMP- or protein kinase C-initiated signaling and
      independent of immediate early gene regulation.

PMID- 14645682
TI  - Uridine binding motifs of human concentrative nucleoside transporters 1 and 3
      produced in Saccharomyces cerevisiae.
AB  - An extensive series of structural analogs of uridine that differed in
      substituents in the sugar and/or base moieties were subjected to inhibitor
      sensitivity assays in a yeast expression system to define uridine structural
      determinants for inhibitors of human concentrative nucleoside transporters 1 and
      3 (hCNT1 and hCNT3). The production of recombinant hCNT1 and hCNT3 in a
      nucleoside-transporter deficient strain of yeast was confirmed by immunoblotting,
      and uridine transport parameters (Km, Vmax) were determined by defining the
      concentration dependence of initial rates of uptake of [3H]uridine by intact
      yeast. The Ki values of uridine analogs were obtained from inhibitory-effect
      curves and converted to binding energies. hCNT1 and hCNT3 recognized uridine
      through distinguishable binding motifs. hCNT1 was sensitive to modifications at
      C(3), less sensitive at C(5') or N(3), and much less sensitive at C(2'). hCNT3
      was sensitive to modifications at C(3'), but much less sensitive at N(3), C(5')
      or C(2'). The changes of binding energy between transporter proteins and
      different uridine analogs suggested that hCNT1 formed hydrogen bonds (H-bonds)
      with C(3')-OH, C(5')-OH, or N(3)-H of uridine, but not with C(2')-OH, whereas
      hCNT3 formed H-bonds to C(3')-OH, but not to N(3)-H, C(5')-OH, and C(2')-OH. Both
      transporters barely tolerated modifications at C(3') or inversion of
      configurations at C(2')orC(3'). The binding profiles identified in this study can
      be used to predict the potential transportability of nucleoside analogs,
      including anticancer or antiviral nucleoside drugs, by hCNT1 and hCNT3.

PMID- 14645683
TI  - PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from
      lipopolysaccharide-induced septic shock.
AB  - Septic shock is the most common cause of death in intensive care units, and no
      effective treatment is available at present. Lipopolysaccharide (LPS) is the
      primary mediator of Gram-negative sepsis by inducing the production of macrophage
      derived proinflammatory cytokines, in which activation of nuclear factor-kappaB
      (NF-kappaB) plays an important role. PC-SPES is an eight-herb mixture active
      against a variety of malignancies, including prostate cancer and leukemia. In
      this study, we demonstrated that PC-SPES inhibited the LPS-induced NF-kappaB
      reporter activity in RAW264.7 macrophages. Electrophoretic mobility shift assay
      showed that PC-SPES inhibited the binding of NF-kappaB to specific DNA sequences;
      however, it did not affect either degradation of inhibitory kappaBalpha or
      nuclear translocation of NF-kappaB. Also, we explored the effect of PCSPES on LPS
      induced mitogen-activated protein (MAP) kinase signaling; PC-SPES did not affect
      LPS-induced phosphorylation of MAP kinases, including c-Jun NH2-terminal kinase,
      p38, and extracellular signal-regulated kinase 1/2. Moreover, PC-SPES decreased
      the production of proinflammatory cytokines and inducible enzymes, such as tumor
      necrosis factor (TNF) alpha, interleukin (IL)-1beta, IL-6, cyclooxygenase-2, as
      well as inducible nitric-oxide synthase in RAW264.7 macrophages and peritoneal
      macrophages from C57BL/6 mice after the cells were stimulated by either LPS or
      LPS and interferon-gamma. Furthermore, PC-SPES rescued C57BL/6 mice from death
      caused by LPS-induced septic shock in conjunction with decreased serum levels of
      TNFalpha and IL-1beta. Together, PC-SPES is a potent inhibitor of NF-kappaB and
      might be useful for the treatment of sepsis and inflammatory diseases.

PMID- 14645684
TI  - A new principle for tight junction modulation based on occludin peptides.
AB  - The aim of this study was to investigate whether peptides from the extracellular
      loops of the tight junction protein occludin could be used as a new principle for
      tight junction modulation. Peptides of 4 to 47 amino acids in length and covering
      the two extracellular loops of the tight junction protein occludin were
      synthesized, and their effect on the tight junction permeability in Caco-2 cells
      was investigated using [14C]mannitol as a para-cellular marker. Lipopeptide
      derivatives of one of the active occludin peptides (OPs), synthesized by adding a
      lipoamino acid containing 14 carbon atoms (C14-) to the N terminus of the
      peptide, were also investigated. Peptides corresponding to the N terminus of the
      first extracellular loop of occludin increased the permeability of the tight
      junctions without causing short-term toxicity. However, the peptides had an
      effect only when added to the basolateral side of the cells, which could be
      partly explained by degradation by apical peptidases and aggregate formation. By
      contrast, the lipopeptide C14-OP90-103, which protects the peptide from
      degradation and aggregation, displayed a rapid apical effect. The l- and d
      diastereomers of C14-OP90-103 had distinctly different effects. The d-isomer,
      which releases intact OP90-103 from the lipoamino acid, displayed a rapid and
      transient increase in tight junction permeability. The l-isomer, which releases
      OP90-103 more rapidly, gave a more sustained increase in tight junction
      permeability. In conclusion, C14-OP90-103 represents a prototype of a new class
      of tight junction modulators that act on the extracellular domains of tight
      junction proteins.

PMID- 14645685
TI  - The mouse RACK1 gene is regulated by nuclear factor-kappa B and contributes to
      cell survival.
AB  - Receptor for activated C kinase 1 (RACK1) is a multifunctional, WD motif
      containing protein important in regulating several cell surface receptors and
      intracellular protein kinases. To better understand its function, we cloned the
      mouse RACK1 gene and found it contains eight exons and seven introns, and maps to
      mouse chromosome 11B1.2-1.3. Promoter analysis identified NF-kappaB as an
      important transcription factor for promoter activity. In PC-12 cells, nerve
      growth factor (NGF), which activates nuclear factor-kappaB (NF-kappaB),
      maintained RACK1 levels and promoted cell survival in serum-free medium.
      Inhibitors of NF-kappaB activation blocked NGF-stimulated survival and RACK1
      expression, whereas transgenic expression of RACK1 promoted survival in cells
      deprived of serum and NGF. Thus, RACK1 gene expression is induced by NF-kappaB
      and RACK1 contributes to NF-kappaB-mediated cell survival.

PMID- 14645686
TI  - Pharmacological and genetic analysis of 90-kDa heat shock isoprotein-aryl
      hydrocarbon receptor complexes.
AB  - The 90-kDa heat shock protein (Hsp90) is an abundant chaperone that regulates a
      diverse set of intracellular signaling proteins. Drugs that inhibit Hsp90
      activity have been useful in the identification of novel Hsp90-dependent
      signaling pathways. One class of inhibitory compounds disrupts Hsp90-dependent
      processes by binding to the N-terminal ATPase/p23-binding domain of Hsp90,
      whereas a second inhibitor class binds within the C-terminal domain. We used
      signaling by aryl hydrocarbon receptor (AhR), an Hsp90-dependent transcription
      factor, as a functional probe to study the effects of Hsp90 inhibitors in yeast
      strains with deletion mutations of individual Hsp90 and p23 cochaperone genes.
      The more abundant and constitutively expressed Hsp90 isoform, Hsc82, functioned
      best in supporting AhR signaling. Deletion of the more inducible isoform, Hsp82,
      had no effect on signaling. AhR complexes containing Hsc82 were preferentially
      sensitive to the effects of low concentrations of the N-terminal inhibitors
      radicicol and herbimycin A. However, both Hsp90 isoforms were equally sensitive
      to the AhR-specific effects of novobiocin, which binds to the C terminus. Hsp90
      inhibitors had no preferential effects on AhR signaling in strains that lacked
      p23, suggesting that the inhibitors exert their effects through a p23-independent
      mechanism. In contrast, overexpression of p23 buffered the effects of radicicol
      and herbimycin A, but not novobiocin, on AhR signaling. The data collectively
      suggest preferential use or function of the Hsc82 isoprotein in AhR signaling and
      provide new insight into the effects of three structurally unrelated Hsp90
      inhibitors.

PMID- 14645687
TI  - Allosteric enhancers of A1 adenosine receptors increase receptor-G protein
      coupling and counteract Guanine nucleotide effects on agonist binding.
AB  - Endogenous ligands of G protein-coupled receptors bind to orthosteric sites that
      are topologically distinct from allosteric sites. Certain aminothiophenes such as
      (2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluromethyl)-phenyl]-methanone (PD81,723)
      and 2-amino-4,5,6,7-tetrahydro-benzo[b]thiophen-3-yl)-biphenyl-4-yl-methanone
      (ATL525) are positive allosteric regulators, or enhancers, of the human A1
      adenosine receptor (A1AR). In equilibrium binding assays, 125I-N6
      aminobenzyladenosine (125I-ABA) binds to two affinity states of A1AR with KD-high
      (0.33 microM) and KD-low ( approximately 10 nM). Enhancers have little effect on
      KD-high but convert all A1AR binding sites to the high-affinity state. Enhancers
      decrease the potency of guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) as an
      inhibitor of agonist binding by 100-fold and increase agonist-stimulated guanine
      nucleotide exchange. The association of 125I-ABA to high-affinity receptors on
      Chinese hamster ovary (CHO)-hA1 membranes does not follow theoretical single-site
      association kinetics but is approximated by a bi-exponential equation with t1/2
      values of 1.85 and 12.8 min. Allosteric enhancers selectively increase the number
      of slow binding sites, possibly by stabilizing newly formed receptor-G protein
      complexes. A new rapid assay method scores enhancer activity on a scale from 0 to
      100 based on their ability to prevent the rapid dissociation of 125I-ABA from
      A1AR in response to GTPgammaS. Compared with PD81,723, ATL525 (100 microM) scores
      higher (27 versus 79) and has less antagonist activity. ATL525 functionally
      enhances A1 signaling to inhibit cAMP accumulation in CHO-hA1 cells. These data
      suggest that simultaneously binding orthosteric and allosteric enhancer ligands
      convert the A1AR from partly to fully coupled to G proteins and prevents rapid
      uncoupling upon binding of GTPgammaS.

PMID- 14645688
TI  - Serine 447 in the carboxyl tail of human VPAC1 receptor is crucial for agonist
      induced desensitization but not internalization of the receptor.
AB  - The VPAC1 receptor for vasoactive intestinal peptide (VIP) belongs to the class
      II family of G protein-coupled receptors and is coupled to Gs protein/adenylyl
      cyclase. We assessed whether 10 different Ser/Thr residues in human VPAC1
      receptor intracellular domains play a role in the process of VIP-induced
      desensitization/internalization by performing a site-directed mutagenesis study.
      The Ser/Thr residues mutated to Ala include potential G protein-coupled receptor
      kinase, protein kinase A and protein kinase C targets that are of particular
      interest for VPAC1 receptor desensitization. The data show that when Chinese
      hamster ovary cells expressing wild-type receptors were pretreated for 5 min with
      VIP (50 nM), receptor desensitization occurred with a 10-fold right shift of the
      ED50 for adenylyl cyclase activation. When the construct with the widest span of
      mutations was studied, there was no longer any short-term desensitization. By
      using constructs with fewer and fewer mutations, we identified Ser447 in the C
      terminal tail to be crucial for rapid desensitization. We also showed that Ser447
      plays an essential role for VIP-induced VPAC1 phosphorylation in Chinese hamster
      ovary cells. Furthermore, we demonstrated that none of the mutated Ser/Thr
      residues was involved in down-regulation after a 12-h treatment of cells with 50
      nM VIP. Neither were they involved in VIP and VIP-induced receptor
      internalization as shown using a novel fluorescein-tagged VIP and VPAC1 receptor
      bearing a Flag epitope in the N-terminal domain and a green fluorescent protein
      at the C terminus. We conclude that Ser447, a likely G protein-coupled receptor
      kinase target, is crucial for VIP-induced phosphorylation and rapid
      desensitization of VPAC1 receptor.

PMID- 14645689
TI  - Closing and inactivation potentiate the cocaethylene inhibition of cardiac sodium
      channels by distinct mechanisms.
AB  - Cocaethylene, a metabolite of cocaine and alcohol, is a potent inhibitor of the
      cardiac (Nav1.5) sodium channel heterologously expressed in Xenopus laevis
      oocytes. Cocaethylene produces minimal tonic block under resting conditions but
      causes a potent use-dependent inhibition during repetitive depolarization and a
      hyperpolarizing shift in the steady-state inactivation. The data are consistent
      with a state-dependent binding mechanism, which has high affinity for inactivated
      channels (KI = 17 microM) and low affinity for resting channels (KR = 185 micro).
      Mutations of the interdomain D3-D4 linker eliminated rapid inactivation and
      weakened the cocaethylene inhibition, consistent with an important role for fast
      inactivation in cocaethylene binding. A rapid component of cocaethylene
      inhibition was observed in a noninactivating mutant of Nav1.5 that was tightly
      linked to channel opening and displayed properties consistent with a pore
      blocking mechanism. Hyperpolarization caused the noninactivating mutant channel
      to close, trapping cocaethylene and slowing the recovery. Mutation of a conserved
      isoleucine (I1756C) located near the extracellular end of the D4S6 segment
      accelerated the recovery of the noninactivating channel, suggesting that this
      mutation facilitates cocaethylene untrapping, which seems to be the rate-limiting
      step in the recovery when the channel is closed. This contrasts with the rapidly
      inactivating channel, where the I1756C mutation did not alter the recovery from
      cocaethylene inhibition. The data suggest that additional mechanisms, such as
      more stable cocaethylene binding, may be a more important determinant of recovery
      kinetics when the channels are inactivated. The data indicate that deactivation
      and inactivation slow the recovery and potentiate the cocaethylene inhibition of
      the Nav1.5 channel by distinct mechanisms.

PMID- 14645690
TI  - Peroxisome proliferator-activated receptor isoform expression changes in human
      gestational tissues with labor at term.
AB  - Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear
      receptors that are involved in lipid metabolism, differentiation, proliferation,
      cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, 
      delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the
      amnion, choriodecidua, and placenta, and its level of expression was unchanged
      with labor. To evaluate whether PPAR-alpha and -delta subtypes are present in
      intrauterine tissues, placentae were obtained from women at term after
      spontaneous vaginal delivery (TSL; n = 15) and elective caesarean section before
      labor (TNL; n = 15). Northern blot analyses were used to evaluate the mRNA for
      PPARs. Activities of PPARs were assessed using JEG3 choriocarcinoma cells
      transfected with a PPAR-response element reporter construct (pTK-PPREx3-luc) and
      treated with PPAR ligands. The PPAR-gamma-specific ligand rosiglitazone induced
      PPAR response element (PPRE)-mediated activity in a concentration-dependent
      manner, whereas the PPAR-gamma-specific irreversible inhibitor GW9662 fully
      inhibited this induction. However, GW9662 only partially inhibited 15-deoxy
      Delta12,14-prostaglandin J2 (15d-PGJ2)-induced luciferase activity, suggesting
      that 15d-PGJ2 may also activate either of the other isoforms. PPAR-alpha and 
      delta are expressed in the amnion, choriodecidua, and placental villous tissues.
      In the amnion, although for PPAR-alpha no significant difference in expression
      was observed with labor, PPAR-delta expression increased significantly (p <
      0.001). In the choriodecidua, expression of PPAR-alpha declined with labor (p <
      0.01), whereas, as in the amnion, PPAR-delta expression increased (p < 0.05). In
      the placenta, both PPAR-alpha and -delta expression increased with labor (p <
      0.005). The changes observed with labor suggest that regulation of PPAR
      expression and function may have roles to the mechanisms that maintain pregnancy
      or initiate labor.

PMID- 14645691
TI  - Validation of cDNA microarray gene expression data obtained from linearly
      amplified RNA.
AB  - BACKGROUND: DNA microarray technology has permitted the analysis of global gene
      expression profiles for several diseases, including cancer. However, standard
      hybridisation and detection protocols require micrograms of mRNA for microarray
      analysis, limiting broader application of this technology to small excisional
      biopsies, needle biopsies, and/or microdissected tissue samples. Therefore,
      linear amplification protocols to increase the amount of RNA have been developed.
      The correlation between the results of microarray experiments derived from non
      amplified RNA and amplified samples needs to be evaluated in detail. METHODS:
      Total RNA was amplified and replicate hybridisation experiments were performed
      with linearly amplified (aRNA) and non-amplified mRNA from tonsillar B cells and
      the SUDHL-6 cell line using cDNA microarrays containing approximately 4500 genes.
      The results of microarray differential expression using either source of RNA
      (mRNA or aRNA) were also compared with those found using real time quantitative
      reverse transcription polymerase chain reaction (QRT-PCR). RESULTS: Microarray
      experiments using aRNA generated reproducible data displaying only small
      differences to data obtained from non-amplified mRNA. The quality of the starting
      total RNA template and the concentration of the promoter primer used to
      synthesise cDNA were crucial components of the linear amplification reaction.
      Approximately 80% of selected upregulated and downregulated genes identified by
      microarray analysis using linearly amplified RNA were confirmed by QRT-PCR using
      non-amplified mRNA as the starting template. CONCLUSIONS: Linear RNA
      amplification methods can be used to generate high fidelity microarray expression
      data of comparable quality to data generated by microarray methods that use non
      amplified mRNA samples.

PMID- 14645692
TI  - Cell cycle regulation in patients with intestinal metaplasia at the gastro
      oesophageal junction.
AB  - BACKGROUND/AIMS: The incidence of oesophageal adenocarcinoma is increasing
      rapidly and this may be related to the presence of intestinal metaplasia (IM) at
      the gastro-oesophageal junction (GOJ). Recent studies have distinguished two
      subtypes of IM at the GOJ: short segment Barrett's oesophagus (SSBO) and IM at a
      normal squamo-columnar junction (IMNSCJ). Because abnormal expression of cell
      cycle regulators is common in cancer and precancerous states, cell cycle
      regulation was studied in patients with IM at the GOJ. METHODS: Biopsy samples
      and resected materials were identified from patients with SSBO (10), IMNSCJ (14),
      a normal SCJ with (14) and without (12) inflammation, conventional Barrett's
      oesophagus (BO) (12), and oesophageal adenocarcinoma (12). Sections were stained
      with antibodies to p21, p27, p53, Ki67, cyclin D1, and c-erbB2 and were assessed
      independently by two observers, using predetermined criteria. RESULTS: Patients
      with oesophageal adenocarcinoma showed high expression of c-erbB2, p53, p27, and
      Ki67. Patients with BO showed expression of c-erbB2 but little expression of
      other markers. Greatly increased expression of cyclin D1 was seen in patients
      with IMNSCJ. The expression of all other markers was similar in patients with
      IMNSCJ and those with SSBO. Cyclin D1 and c-erbB-2 were coexpressed in patients
      with SSBO and IMNSCJ, and their expression was associated with the presence of
      p53 and p21. CONCLUSIONS: Although the proposed aetiologies of SSBO (gastro
      oesophageal reflux) and IMNSCJ (Helicobacter pylori infection) differ, the cell
      cycle response is similar and both may have malignant potential.

PMID- 14645693
TI  - Expression of P-cadherin, but not E-cadherin or N-cadherin, relates to
      pathological and functional differentiation of breast carcinomas.
AB  - AIMS: To compare the expression of the cell adhesion molecules P-cadherin, N
      cadherin, and E-cadherin in invasive and in situ breast carcinomas relative to
      clinicopathological features (size, node status, type, grade, and receptors) to
      determine whether expression patterns relate to specific tumour characteristics.
      METHODS: Using immunohistochemistry, 110 invasive and in situ breast carcinomas
      were examined for the presence, extent, and localisation of all three cadherins.
      Findings were related to tumour size, type, grade, node status, oestrogen (ER),
      progesterone, and epidermal growth factor receptor (EGFR) expression for invasive
      carcinomas and to grade and receptors for in situ carcinomas. RESULTS: P-cadherin
      was detected in 40% of invasive carcinomas, N-cadherin in 30%, and E-cadherin in
      81%. For invasive carcinomas, the presence of P-cadherin significantly correlated
      with high grade, lack of ER and presence of EGFR, but not tumour size or node
      status. Carcinomas containing P-cadherin could be put into three categories
      dependent upon receptor and E-cadherin profile. There were no correlations
      between E/N-cadherin and size, grade, node status, or receptors. Three of 16
      infiltrating lobular carcinomas expressed cytoplasmic but none membranous E
      cadherin, and P-cadherin and N-cadherin were present in four carcinomas of this
      type. E-cadherin was found in all ductal carcinomas in situ, P-cadherin in a
      proportion of high grade tumours, and N-cadherin in a mixture of grades.
      CONCLUSION: P-cadherin but not E/N-cadherin expression in breast carcinomas shows
      a strong correlation with higher grade (poorer differentiation), lack of ERs, and
      presence of EGFR, and its expression may aid in the further subdivision of high
      grade carcinomas.

PMID- 14645694
TI  - Immunohistochemical prognostic index for breast cancer in young women.
AB  - AIMS: Women under 35 years of age comprise a small proportion of patients with
      breast cancer, but determining their prognosis can be difficult. This
      prospective, multivariate study looked at several factors with the aim of
      obtaining a useful index to evaluate the prognosis of these women. METHODS: In
      total, 108 patients below 35 years of age affected by invasive ductal carcinoma
      without distant metastasis were studied. The mean duration of the follow up
      period was six years. Histopathological (tumour size, histological grade, and
      lymph node stage) and immunohistochemical (c-erbB-2, p53, oestrogen receptor, and
      progesterone receptor) factors were measured in all patients, and the Nottingham
      prognostic index (NPI) was then calculated. An immunohistochemical prognostic
      index (IHPI) was created using the arithmetic sum of the four individual
      immunohistochemical factors. RESULTS: In univariate assessment of survival, all
      the studied factors yielded a significant association with either overall
      survival or disease free survival, except for c-erbB-2 and p53 with disease free
      survival. In univariate calculation of risk, all the factors gave significant
      results; however, in multivariate analysis only tumour size, histological grade,
      and progesterone receptor were significant. Both NPI and IHPI correlated
      significantly with prognosis. In multivariate regression analysis, IHPI
      correlated with tumour size and there was a significant interaction between both
      variables. CONCLUSION: IHPI is very useful in determining the prognosis of
      tumours < or = 2 cm and of moderate use for tumours > 2, although it has no use
      in tumours > 5 cm.

PMID- 14645695
TI  - Expression of the cell cycle regulatory proteins p34cdc2, p21waf1, and p53 in
      node negative invasive ductal breast carcinoma.
AB  - AIMS: To look for correlations between expression of cell cycle regulatory
      proteins p34(cdc2), p21(WAF1), and p53 in node negative invasive ductal breast
      carcinoma, or between these proteins and clinicopathological parameters, and to
      assess their prognostic value. METHODS: Immunohistochemistry using formalin
      fixed, paraffin wax embedded sections from 94 breast carcinomas. Adjacent benign
      epithelial breast tissue was available in 74 cases. Median follow up was 72
      months. RESULTS: Nuclear and cytoplasmic p34(cdc2) expression was seen in 80 and
      62 tumours, respectively; nuclear expression was seen in adjacent benign
      epithelium in 12 cases. p21(WAF1) and p53 were positive in 48 and 21 tumours,
      respectively. High expression of p34(cdc2) in neoplastic nuclei was associated
      with higher histological grade and p53 expression, but not with tumour size,
      steroid receptor status, patient age, menopausal status, recurrence, metastasis,
      disease free survival (DFS), or overall survival (OS). p34(cdc2) in tumour
      cytoplasm was associated with p34(cdc2) nuclear positivity, high tumour grade,
      and DFS in univariate but not multivariate analysis. In contrast, p34(cdc2)
      expression in benign tissue independently predicted DFS and OS in univariate and
      multivariate analysis. Expression of p53 was associated with high tumour grade
      and negative steroid receptors, but not with recurrence, metastasis, DFS, or OS.
      p21(WAF1) expression was not associated with the examined parameters.
      CONCLUSIONS: p34(cdc2), p21(WAF1), and p53 expression does not predict outcome in
      node negative breast carcinoma, although p34(cdc2) expression in benign tissue is
      related to prognosis. The association between p34(cdc2) and p53 implicates p53 in
      G2-M cell cycle checkpoint control, possibly via mediators unrelated to
      p21(WAF1).

PMID- 14645696
TI  - Increased cyclin D1 expression in cancer of the ampulla of Vater: relevance to
      nuclear beta catenin accumulation and k-ras gene mutation.
AB  - AIMS: Several studies have reported that dysregulation of beta catenin or k-ras
      mutation promotes cyclin D1 expression. This study investigated the relation
      between cyclin D1 expression and clinicopathological parameters in carcinoma of
      the ampulla of Vater (CAV), and also assessed the relation between increased
      cyclin D1 expression and beta catenin/k-ras status in this series. METHODS:
      Thirty CAVs were evaluated for cyclin D1 expression by immunohistochemistry in
      relation to patient clinicopathological features. Aberrant beta catenin
      expression and k-ras mutation were also investigated by immunostaining and direct
      sequencing, and related to cyclin D1 expression. RESULTS: Increased cyclin D1
      expression was seen in 17 of 30 CAVs and was significantly correlated with tumour
      cell proliferation and disease free survival time (p = 0.018, p = 0.018,
      respectively). Nuclear accumulation of beta catenin was found in nine of 30
      cases, including four cases with missense mutations in exon 3 of CTNNB-1, and was
      significantly correlated with increased cyclin D1 expression (p = 0.003). k-ras
      gene mutation was detected in 12 of 30 cases, and was also significantly
      correlated with increased cyclin D1 expression (p = 0.026). Overall, 14 of 17
      CAVs with increased cyclin D1 expression showed nuclear accumulation of beta
      catenin and/or k-ras mutation. CONCLUSIONS: Increased cyclin D1 expression
      appears to be associated with tumour proliferation and poorer clinical outcome in
      CAV. It is also associated with both aberrant beta catenin expression and k-ras
      mutation. These results are consistent with the in vitro data that cyclin D1 can
      be transactivated by activated beta catenin-T cell factor/LEF and k-ras pathways.

PMID- 14645697
TI  - Laminin 5 gamma 2 chain expression: a marker of early invasiveness in colorectal
      adenomas.
AB  - AIM: Polyps of the colon and rectum are considered to be premalignant lesions in
      the development of colorectal cancer. However, knowledge of how normal epithelial
      cells gain invasive properties is limited. Laminin 5 gamma 2 chain expression was
      investigated to determine the role of laminin 5 as a marker of potential
      invasiveness in colorectal polyps. MATERIAL/METHODS: Sixty seven polyps of
      different types (15 hyperplastic polyps, 12 serrated adenomas, 16 tubular
      adenomas, and 24 adenomas with a villous component) were assessed for gamma 2
      chain expression of laminin 5 by immunohistochemistry on archival, paraffin wax
      embedded sections. RESULTS: Ten polyps stained positive and the number of polyps
      expressing the laminin 5 gamma 2 chain increased significantly as the phenotype
      of the adenomas became more atypical: none of the 15 hyperplastic polyps, two of
      the 16 tubular adenomas (12.5%), and six of the 24 adenomas with a villous
      component (25%) were positive. Two of 12 (17%) serrated adenomas, regarded as a
      distinct form of colorectal neoplasia, showed gamma 2 chain expression.
      Furthermore, laminin 5 gamma 2 chain expression correlated with lesion size.
      Polyps smaller than 10 mm expressed the gamma 2 chain less frequently than did
      those equal to or larger than 10 mm. CONCLUSION: Laminin 5 gamma 2 chain
      expression was found to increase progressively towards a more atypical phenotype
      of adenoma. The results suggest that, in the future, laminin 5 gamma 2 chain
      expression may be used as an indicator of incipient malignant transformation of a
      benign colorectal adenoma.

PMID- 14645698
TI  - Nuclear beta catenin as a potential prognostic and diagnostic marker in patients
      with colorectal cancer from Hong Kong.
AB  - AIMS: To study the expression of nuclear beta catenin in patients with colorectal
      cancer, colorectal adenoma, and colorectal polyps to elucidate its role in
      carcinogenesis, and its potential for prognosis and diagnosis. METHODS: The
      expression of nuclear beta catenin was studied by immunohistochemistry using
      paraffin wax embedded specimens. Sixty specimens each of colorectal carcinoma,
      colorectal adenoma, colorectal polyp, and normal colorectal specimens were
      analysed. The potential for prognosis was assessed by correlating nuclear beta
      catenin expression in 60 and 75 patients with colorectal cancer with lymph node
      metastasis and survival, respectively. The diagnostic capacity was explored by
      comparing nuclear beta catenin expression in 60 patients with colorectal cancer
      with other cytokeratin 20 (CK20) positive adenocarcinomas, namely: 30 colonic
      mucinous adenocarcinomas, 30 gastric adenocarcinomas, 27 pancreatic
      adenocarcinomas, and 12 ovarian mucinous adenocarcinomas. RESULTS: Nuclear beta
      catenin expression was highly associated with progression of colorectal tissue
      from normal epithelial tissue, polyps, adenomas, to carcinomas (r = 0.875; p <
      0.0001). Nineteen patients with colorectal adenoma who subsequently developed
      colorectal carcinoma had higher nuclear beta catenin expression than those with
      colorectal adenomas alone (p < 0.0001). Moreover, those patients with colorectal
      cancer and high nuclear beta catenin expression had a higher incidence of lymph
      node metastasis (chi(2) = 16.99; p < 0.005) and shorter overall survival (p <
      0.0001). Finally, nuclear beta catenin expression in colorectal adenocarcinomas
      was significantly higher than in other CK20 positive adenocarcinomas.
      CONCLUSIONS: Nuclear beta catenin expression is a potential prognostic factor in
      patients with colorectal cancer, and together with CK20, it could be used to
      identify colorectal carcinoma in the Hong Kong population.

PMID- 14645699
TI  - Inverse correlation between high level expression of cyclin E and proliferation
      index in transitional cell carcinoma of the bladder.
AB  - BACKGROUND/AIMS: Overexpression of the G1 cyclins, D1 and E, and/or
      downregulation of p27(Kip1) allow uncontrolled tumour cell proliferation. This
      study investigated the relation between these three cell cycle proteins and
      tumour proliferation in bladder cancer. METHOD: Nuclear expression of cyclin D1,
      cyclin E, and p27(Kip1) was determined immunohistochemically in 52 primary
      transitional cell carcinomas, and the Ki-67 proliferation marker was also
      assessed. For each protein, the percentage of positive tumour cell nuclei was
      determined and analysed as a continuous variable. RESULTS: Advancing tumour grade
      and pathological stage were accompanied by increasing proliferation indices, but
      decreasing p27(Kip1) and cyclin D1 expression, with no significant change in
      cyclin E expression. Overall, cyclin D1 and E expression did not correlate with
      proliferation. However, in cyclin D1 overexpressing tumours (> or = 5% nuclei
      positive), the level of cyclin D1 expression positively correlated with
      proliferation. The correlation between cyclin E expression and proliferation
      changed from positive to negative with increasing levels of cyclin E expression,
      accompanied by a coordinate increase in p27(Kip1) expression. Overall, there was
      an inverse association between p27(Kip1) expression and proliferation. However, a
      subset of tumours displayed high proliferation indices despite high p27(Kip1)
      expression. The G1 cyclin index (sum of the level of expression of cyclins D1 and
      E) correlated positively with proliferation in superficial but not muscle
      invasive tumours. This correlation was stronger when the G1 cyclin index was
      adjusted for p27(Kip1) expression. CONCLUSION: These findings support a role for
      these proteins in the proliferation, differentiation, and progression of bladder
      transitional cell carcinomas.

PMID- 14645700
TI  - Tempero-spatial dissociation between the expression of Fas and apoptosis after
      coronary occlusion.
AB  - AIMS: To explore the role of Fas in cardiomyocytic apoptosis induced by ischaemia
      through determining the histological relation between Fas expression and
      apoptosis in rat myocardium during ischaemia/infarction. METHODS: The myocardial
      ischaemia model was produced by ligating the left coronary artery in Sprague
      Dawley rats. The rats were killed from 10 minutes to seven days after surgery.
      Apoptotic myocardial cells were detected by the in situ terminal deoxynucleotidyl
      transferase mediated nick end labelling method, and the expression of Fas by
      immunohistochemistry and western blotting. RESULTS: Cardiomyocytic apoptosis
      appeared from three to 36 hours after ischaemia. The expression of Fas could be
      detected by western blot from before surgery to seven days of ischaemia.
      Apoptosis and the expression of Fas in the cardiomyocytes appeared in different
      regions of the myocardium: apoptosis in the ischaemic region, Fas in the regions
      surrounding ischaemic myocardium. CONCLUSION: These results suggest that there is
      a tempero-spatial dissociation between the expression of Fas and apoptosis after
      coronary occlusion. Fas might not directly regulate the apoptosis of
      cardiomyocytes induced by ischaemia.

PMID- 14645701
TI  - Development of molecular methods for the identification of aspergillus and
      emerging moulds in paraffin wax embedded tissue sections.
AB  - BACKGROUND/AIMS: Invasive infection with emerging moulds is increasing in
      incidence and reliable methods for speciating these organisms in tissue sections
      need to be developed. METHODS: Two methods for extracting fungal DNA from
      paraffin wax embedded tissue sections, based on the TaKaRa DEXPAT kit and QIAamp
      DNA mini kit, were optimised and compared. DNA was amplified by PCR using pan
      fungal probes, and detected by Southern blot hybridisation using a high
      stringency method with a probe specific for Aspergillus fumigatus and A flavus.
      RESULTS: The method based on the TaKaRa DEXPAT kit, with additional steps using
      lyticase and ethanol precipitation, was superior. Less than 10 conidia were
      detectable using spiked samples and a positive result was obtained with 100% of
      clinical samples known to be culture positive for A fumigatus. Other moulds could
      be identified by using species specific probes or by sequencing PCR products.
      CONCLUSIONS: The method based on the TaKaRa DEXPAT kit could detect less than 10
      conidia/sample. The method allowed accurate identification of A fumigatus and A
      flavus and other species could be identified using species specific probes or by
      DNA sequencing. These methods will provide a valuable diagnostic tool for both
      patient management and future antifungal and epidemiological studies.

PMID- 14645702
TI  - Evolution of genomic diversity and sex at extreme environments: fungal life under
      hypersaline Dead Sea stress.
AB  - We have found that genomic diversity is generally positively correlated with
      abiotic and biotic stress levels (1-3). However, beyond a high-threshold level of
      stress, the diversity declines to a few adapted genotypes. The Dead Sea is the
      harshest planetary hypersaline environment (340 g.liter-1 total dissolved salts,
      approximately 10 times sea water). Hence, the Dead Sea is an excellent natural
      laboratory for testing the "rise and fall" pattern of genetic diversity with
      stress proposed in this article. Here, we examined genomic diversity of the
      ascomycete fungus Aspergillus versicolor from saline, nonsaline, and hypersaline
      Dead Sea environments. We screened the coding and noncoding genomes of A.
      versicolor isolates by using >600 AFLP (amplified fragment length polymorphism)
      markers (equal to loci). Genomic diversity was positively correlated with stress,
      culminating in the Dead Sea surface but dropped drastically in 50- to 280-m-deep
      seawater. The genomic diversity pattern paralleled the pattern of sexual
      reproduction of fungal species across the same southward gradient of increasing
      stress in Israel. This parallel may suggest that diversity and sex are
      intertwined intimately according to the rise and fall pattern and adaptively
      selected by natural selection in fungal genome evolution. Future large-scale
      verification in micromycetes will define further the trajectories of diversity
      and sex in the rise and fall pattern.

PMID- 14645703
TI  - Cancerous stem cells can arise from pediatric brain tumors.
AB  - Pediatric brain tumors are significant causes of morbidity and mortality. It has
      been hypothesized that they derive from self-renewing multipotent neural stem
      cells. Here, we tested whether different pediatric brain tumors, including
      medulloblastomas and gliomas, contain cells with properties similar to neural
      stem cells. We find that tumor-derived progenitors form neurospheres that can be
      passaged at clonal density and are able to self-renew. Under conditions promoting
      differentiation, individual cells are multipotent, giving rise to both neurons
      and glia, in proportions that reflect the tumor of origin. Unlike normal neural
      stem cells, however, tumor-derived progenitors have an unusual capacity to
      proliferate and sometimes differentiate into abnormal cells with multiple
      differentiation markers. Gene expression analysis reveals that both whole tumors
      and tumor-derived neurospheres express many genes characteristic of neural and
      other stem cells, including CD133, Sox2, musashi-1, bmi-1, maternal embryonic
      leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor
      to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells
      migrate, produce neurons and glia, and continue to proliferate for more than 4
      weeks. The results show that pediatric brain tumors contain neural stem-like
      cells with altered characteristics that may contribute to tumorigenesis. This
      finding may have important implications for treatment by means of specific
      targeting of stem-like cells within brain tumors.

PMID- 14645704
TI  - Concerted regulation of skeletal muscle contractility by oxygen tension and
      endogenous nitric oxide.
AB  - It is generally accepted that inhibition of nitric oxide synthase (NOS)
      facilitates, and thus nitric oxide (NO) inhibits, contractility of skeletal
      muscle. However, standard assessments of contractility are carried out at a
      nonphysiological oxygen tension [partial pressure of oxygen (pO2)] that can
      interfere with NO signaling (95% O2). We therefore examined, in normal and
      neuronal NOS (nNOS)-deficient mice, the influence of pO2 on whole-muscle
      contractility and on myocyte calcium flux and sarcomere shortening. Here, we
      demonstrate a significant enhancement of these measures of muscle performance at
      low physiological pO2 and an inhibitory influence at higher physiological pO2,
      which depend on endogenous nNOS. At 95% O2 (which produces oxidative stress;
      muscle core pO2 approximately 400 mmHg), force production is enhanced but control
      of contractility by NO/nitrosylation is greatly attenuated. In addition,
      responsivity to pO2 is altered significantly in nNOS mutant muscle. These results
      reveal a fundamental role for the concerted action of NO and O2 in physiological
      regulation of skeletal muscle contractility, and suggest novel molecular aspects
      of myopathic disease. They suggest further that the role of NO in some cellular
      systems may require reexamination.

PMID- 14645705
TI  - Requirement of p53 targets in chemosensitization of colonic carcinoma to death
      ligand therapy.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits specific
      tumoricidal activity and is under development for cancer therapy. Mismatch-repair
      deficient colonic tumors evade TRAIL-induced apoptosis through mutational
      inactivation of Bax, but chemotherapeutics including Camptosar (CPT-11) restore
      TRAIL sensitivity. However, the signaling pathways in restoring TRAIL sensitivity
      remain to be elucidated. Here, we imaged p53 transcriptional activity in Bax-/-
      carcinomas by using bioluminescence, in vivo, and find that p53 is required for
      sensitization to TRAIL by CPT-11. Small interfering RNAs directed at proapoptotic
      p53 targets reveal TRAIL receptor KILLER/DR5 contributes significantly to TRAIL
      sensitization, whereas Bak plays a minor role. Caspase 8 inhibition protects both
      CPT-11 pretreated wild-type and Bax-/- HCT116 cells from TRAIL-induced apoptosis,
      whereas caspase 9 inhibition only rescued the wild-type HCT116 cells from death
      induced by TRAIL. The results suggest a conversion in the apoptotic mechanism in
      HCT116 colon carcinoma from a type II pathway involving Bax and the mitochondria
      to a type I pathway involving efficient extrinsic pathway caspase activation. In
      contrast to Bax-/- cells, Bak-deficient human cancers undergo apoptosis in
      response to TRAIL or CPT-11, implying that these proteins have nonoverlapping
      functions. Our studies elucidate a mechanism for restoration of TRAIL sensitivity
      in MMR-deficient Bax-/- human cancers through p53-dependent activation of
      KILLER/DR5 and reconstitution of a type I death pathway. Efforts to identify
      agents that up-regulate DR5 may be useful in cancer therapies restoring TRAIL
      sensitivity.

PMID- 14645706
TI  - Differential G protein-coupled cannabinoid receptor signaling by anandamide
      directs blastocyst activation for implantation.
AB  - Mammalian fertility absolutely depends on synchronized development of the
      blastocyst to the stage when it is competent to implant, and the uterus to the
      stage when it is receptive to implantation. However, the molecular basis for the
      reciprocal interaction between the embryo and the uterus remains largely
      unexplored. One potentially important mechanism involves signaling between an
      evolutionarily conserved G protein-coupled protein cannabinoid receptor, CB1,
      that is expressed at high levels on the surface of the trophectoderm and
      anandamide (N-arachi-donoylethanolamine), an endocannabinoid ligand found to be
      produced at higher levels by the uterus before implantation and then down
      regulated at the time of implantation. Using genetic, pharmacological, and
      physiological approaches, we show here that anandamide within a very narrow range
      regulates blastocyst function and implantation by differentially modulating
      mitogen-activated protein kinase signaling and Ca2+ channel activity via CB1
      receptors. Anandamide at a low concentration (7 nM) induces extracellular
      regulated kinase phosphorylation and nuclear translocation in trophectoderm cells
      without influencing Ca2+ channels, and renders the blastocyst competent for
      implantation in the receptive uterus. In contrast, anandamide at a higher
      concentration (28 nM) inhibits Ca2+ channel activity and blastocyst competency
      for implantation without influencing mitogen-activated protein kinase signaling.
      Besides uncovering a potentially important regulatory mechanism for synchronizing
      blastocyst and uterine competency to implantation, this observation has high
      clinical relevance, because elevated levels of anandamide induce spontaneous
      pregnancy loss in women.

PMID- 14645707
TI  - Activity of a type 1 picornavirus internal ribosomal entry site is determined by
      sequences within the 3' nontranslated region.
AB  - We have proposed a cancer treatment modality based on poliovirus chimeras
      replicating under the translational control of an internal ribosomal entry site
      (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES
      causes a neuron-specific propagation deficit and eliminates neurovirulence
      inherent in poliovirus without affecting viral growth in cells derived from
      malignant gliomas. We now report the elucidation of a molecular mechanism
      responsible for the cell type-specific defect mediated by the rhinovirus IRES.
      Rhinovirus IRES function in neuronal cell types depends on specific structural
      elements within the 3' non-translated region of the viral genome. Our
      observations suggest long-range interactions between the IRES and the 3' terminus
      that control IRES-mediated gene expression and virus propagation.

PMID- 14645708
TI  - Mucosal tolerance to E-selectin provides cell-mediated protection against
      ischemic brain injury.
AB  - We have demonstrated that induction of mucosal tolerance to E-selectin, a
      cytokine-inducible adhesion molecule restricted to activating blood vessels,
      prevents ischemic and hemorrhagic stroke in spontaneously hypertensive,
      genetically stroke-prone (SHR-SP) rats. We now examine whether mucosal tolerance
      to E-selectin has protective effects in ischemic brain damage after permanent
      middle cerebral artery occlusion (MCAO) in SHR-SP rats and whether these effects
      are related to generation of regulatory T cells. Rats were exposed to intranasal
      administration of E-selectin every other day for 10 days (single tolerization
      group) or on two tolerization schedules separated by 11 days (booster
      tolerization group). Control groups received PBS on corresponding schedules. MCAO
      was performed 48 h after the last dose of E-selectin or PBS. There were 45.8% and
      37.9% (P < 0.05) decreases of infarction volume in the E-selectin booster group
      compared with the PBS group at 6 and 48 h, respectively. Single tolerization with
      E-selectin had only a slight trend toward a decrease in infarction volume (6.3%).
      CD8-positive cells were decreased in brains of E-selectin booster animals (46.6%,
      P < 0.01) compared with controls; splenocyte-culture supernatant levels of IL-10
      were increased (59.3%, P < 0.05) in E-selectin booster animals. A decrease of
      infarction volume (34%, P < 0.05) was also observed in SHR-SP rats subjected to
      MCAO after adoptive transfer of splenocytes from E-selectin-tolerized compared
      with PBS-tolerized donors. The results indicate that, in addition to preventing
      stroke, mucosal tolerance to E-selectin is cytoprotective. Thus, immunomodulation
      targeted to activated blood vessel segments can both reduce stroke occurrence and
      attenuate brain damage if a stroke supervenes.

PMID- 14645709
TI  - From the Cover: Segmented spiral waves in a reaction-diffusion system.
AB  - Pattern formation in reaction-diffusion systems is often invoked as a mechanism
      for biological morphogenesis. Patterns in chemical systems typically occur either
      as propagating waves or as stationary, spatially periodic, Turing structures. The
      spiral and concentric (target) waves found to date in spatially extended chemical
      or physical systems are smooth and continuous; only living systems, such as
      seashells, lichens, pine cones, or flowers, have been shown to demonstrate
      segmentation of these patterns. Here, we report observations of segmented spiral
      and target waves in the Belousov-Zhabotinsky reaction dispersed in water
      nanodroplets of a water-in-oil microemulsion. These highly ordered chemical
      patterns, consisting of short wave segments regularly separated by gaps, form a
      link between Turing and trigger wave patterns and narrow the disparity between
      chemistry and biology. They exhibit aspects of such fundamental biological
      behavior as self-replication of structural elements and preservation of
      morphology during evolutionary development from a simpler precursor to a more
      complex structure.

PMID- 14645710
TI  - Imaging Tetrahymena ribozyme splicing activity in single live mammalian cells.
AB  - Tetrahymena ribozymes hold promise for repairing genetic disorders but are
      largely limited by their modest splicing efficiency and low production of final
      therapeutic proteins. Ribozyme evolution in intact living mammalian cells would
      greatly facilitate the discovery of new ribozyme variants with high in vivo
      activity, but no such strategies have been reported. Here we present a study
      using a new reporter enzyme, beta-lactamase, to report splicing activity in
      single living cells and perform high-throughput screening with flow cytometry.
      The reporter ribozyme constructs consist of the self-splicing Tetrahymena
      thermophila group I intron ribozyme that is inserted into the ORF of the mRNA of
      beta-lactamase. The splicing activity in single living cells can be readily
      detected quantitatively and visualized. Individual cells have shown considerable
      heterogeneity in ribozyme activity. Screening of Tetrahymena ribozymes with
      insertions in the middle of the L1 loop led to identification of better variants
      with at least 4-fold more final in vivo activity than the native sequence. Our
      work has provided a new reporter system that allows high-throughput screening
      with flow cytometry of single living mammalian cells for a direct and facile in
      vivo selection of desired ribozyme variants.

PMID- 14645711
TI  - An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40
      ligand fusion protein to dendritic cells.
AB  - To develop a method to overcome the anergy that exists in tumor hosts to cancer,
      we have designed an adenoviral vector for the in vivo activation and tumor
      antigen loading of dendritic cells. This adenoviral vector encodes a fusion
      protein composed of an amino-terminal tumor-associated antigen fragment fused to
      the CD40 ligand (CD40L). Subcutaneous injection of an adenoviral vector encoding
      a fusion protein of the human papillomavirus E7 foreign antigen linked to the
      CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7
      positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year. We also
      studied the s.c. injection of a vector carrying the gene for the human MUC-1
      (hMUC-1) self-antigen fused to the CD40L. When this vector was injected into hMUC
      1.Tg mice, which are transgenic for the hMUC-1 antigen, the growth of syngeneic
      hMUC-1-positive LL1/LL2hMUC-1 mouse cancer cells was suppressed in 100% of the
      injected animals. The hMUC-1.Tg mice are anergic to the hMUC-1 antigen before the
      injection of the vector. These experimental results show that it is possible to
      use vector injection to activate a long-lasting cellular immune response against
      self-antigens in anergic animals. The vector-mediated in vivo activation, and
      tumor-associated antigen loading of dendritic cells does not require additional
      cytokine boosting to induce the immune response against the tumor cells. This
      vector strategy may therefore be of use in the development of immunotherapy for
      the many carcinomas in which the hMUC-1 antigen is overexpressed.

PMID- 14645712
TI  - Natural occurrence and synthesis of two new postspinel polymorphs of chromite.
AB  - A high-pressure polymorph of chromite, the first natural sample with the calcium
      ferrite structure, has been discovered in the shock veins of the Suizhou
      meteorite. Synchrotron x-ray diffraction analyses reveal an orthorhombic CaFe2O4
      type (CF) structure. The unit-cell parameters are a = 8.954(7) A, b = 2.986(2) A,
      c = 9.891(7) A, V = 264.5(4) A3 (Z = 4) with space group Pnma. The new phase has
      a density of 5.62 g/cm3, which is 9.4% denser than chromite-spinel. We performed
      laser-heated diamond anvil cell experiments to establish that chromite-spinel
      transforms to CF at 12.5 GPa and then to the recently discovered CaTi2O4-type
      (CT) structure above 20 GPa. With the ubiquitous presence of chromite, the CF and
      CT phases may be among the important index minerals for natural transition
      sequence and pressure and temperature conditions in mantle rocks, shock
      metamorphosed terrestrial rocks, and meteorites.

PMID- 14645713
TI  - Natural killer cells in HIV-1 infection: dichotomous effects of viremia on
      inhibitory and activating receptors and their functional correlates.
AB  - Natural killer (NK) cells play a central role in host defense against various
      pathogens. Functional defects of NK cells in HIV-1 infection as a direct effect
      of abnormal expression or function of inhibitory NK receptors (iNKRs), activating
      natural cytotoxicity receptors (NCRs), and NKG2D have not yet been described.
      This study demonstrates an expansion of the functionally defective CD56-/CD16+
      population of NK cells in viremic versus aviremic patients. We also demonstrate
      that in HIV-infected viremic patients, expression of iNKRs was well conserved and
      that in most cases, there was a trend toward increased expression on NK cells as
      compared with healthy donors. It was also demonstrated that the major activating
      NK receptors, with the exception of NKG2D, were significantly down-regulated. In
      contrast, the expression of iNKRs and activating receptors in HIV-infected
      individuals whose viremia was suppressed to below detectable levels by highly
      active antiretroviral therapy for 2 years or longer was comparable to that of
      healthy donors. Functional tests confirmed that the abnormal expression of the
      activating receptors and of iNKRs was associated with a markedly impaired NK
      cytolytic function. This phenomenon is not attributed to a direct HIV-1 infection
      of NK cells; thus, this study may provide insight into the mechanisms of impaired
      host defenses in HIV-1 viremic patients.

PMID- 14645714
TI  - Structural basis of peptide-carbohydrate mimicry in an antibody-combining site.
AB  - The structure of a complex between the Fab fragment of the antibody (SYA/J6)
      specific for the cell surface O-antigen polysaccharide of the pathogen Shigella
      flexneri Y and an octapeptide (Met-Asp-Trp-Asn-Met-His-Ala-Ala), a functional
      mimic of the O-antigen, has been determined at 1.8-A resolution. Comparison of
      the structure with that of the complex with the pentasaccharide antigen [-->2)
      alpha-L-Rha-(1-->2)-alpha-L-Rha-(1-->3)-alpha-L-Rha-(1-->3)-beta-D-GlcNAc-(1-->2)
      alpha-L-Rha-(1-->] reveals the molecular recognition process by which a peptide
      mimics a carbohydrate in binding to an antibody. The binding modes of the two
      ligands differ considerably. Octapeptide binding complements the shape of the
      combining site groove much better than pentasaccharide binding. Moreover, the
      peptide makes a much greater number of contacts (126), which are mostly van der
      Waals interactions, with the Fab than the saccharide (74). An unusual feature is
      also the involvement of 12 water molecules in mediating hydrogen bonds between
      residues within the peptide or of the peptide and Fab. Despite better shape
      complementarity and greater number of contacts, the octapeptide binds with an
      affinity (KA = 2.5 x 10(5) M-1, measured by calorimetry) only approximately 2
      fold tighter than the pentasaccharide. The structural results are relevant to the
      design of peptide mimetics with improved affinity for use as vaccines.

PMID- 14645715
TI  - Transmembrane phosphoprotein Cbp senses cell adhesion signaling mediated by Src
      family kinase in lipid rafts.
AB  - Cbp, a C-terminal Src kinase (Csk)-binding protein, is a transmembrane
      phosphoprotein that has been implicated in the regulation of the Src family
      kinase (SFK) through recruiting Csk, a negative regulator of SFK, to a membrane
      microdomain of lipid rafts. To examine the contribution of Cbp to cell adhesion
      signaling mediated by SFK, we investigated the kinase responsible for
      phosphorylating Cbp and the mode of phosphorylation during the cell adhesion
      process. The results obtained by using mutant mice or cells that lack Csk and/or
      a member of SFK, Fyn, reveal that Cbp is phosphorylated predominantly by raft
      localized Fyn in vivo. Upon cell adhesion onto fibronectin, Cbp becomes
      transiently phosphorylated (consistent with SFK activation) and recruits Csk to
      lipid rafts. These events are completed before the full activation of focal
      adhesion kinase, indicating that the transient activation and down-regulation of
      SFK in lipid rafts are earlier events in cell adhesion signaling. In Csk
      deficient cells, continuous hyperactivation of SFK leads to continuous
      hyperphosphorylation of Cbp, accompanied by impaired cell spreading and
      migration. Silencing of Cbp by RNA interference also induced impaired cell
      spreading. These findings suggest that Cbp could serve as a sensor of SFK
      activity in early stages of cell adhesion signaling, and that Csk-mediated down
      regulation of SFK is essential to allow dynamic cellular events involved in the
      regulation of cell spreading and migration.

PMID- 14645716
TI  - Studies on the structure and dynamics of the human telomeric G quadruplex by
      single-molecule fluorescence resonance energy transfer.
AB  - We have investigated the structure and unfolding kinetics of the human telomeric
      intramolecular G quadruplex by using single-molecule fluorescence resonance
      energy transfer. An exploration of conformational heterogeneity revealed two
      stable folded conformations, in both sodium- and potassium-containing buffers,
      with small differences between their enthalpies and entropies. Both folded
      conformations can be opened by the addition of a 21-base complementary DNA
      oligonucleotide. The unfolding of both substates occurs at the same rate, which
      showed dependence on the monovalent metal cation present. Temperature-dependence
      studies in 100 mM KCl gave an apparent activation enthalpy and entropy of 6.4 +/-
      0.4 kcal.mol-1 and -52.3 +/- 1.4 cal.mol-1.K-1, respectively, indicating that the
      unfolding is entropically driven and can occur easily. In contrast, in 100 mM
      NaCl the respective values are 14.9 +/- 0.2 kcal.mol-1 and -23.0 +/- 0.8 cal.mol
      1.K-1, suggesting a more significant enthalpic barrier. Molecular modeling
      suggests that the two species are likely to be the parallel and antiparallel
      quadruplex structures. The unfolding free energy barrier is estimated to be
      between 3 and 15 kBT based on Kramers' theory. We conclude that under near
      physiological conditions these structures coexist and can interconvert on a
      minute time scale.

PMID- 14645717
TI  - Cu nanocrystal growth on peptide nanotubes by biomineralization: size control of
      Cu nanocrystals by tuning peptide conformation.
AB  - With recent interest in seeking new biologically inspired device-fabrication
      methods in nanotechnology, a new biological approach was examined to fabricate Cu
      nanotubes by using sequenced histidine-rich peptide nanotubes as templates. The
      sequenced histidine-rich peptide molecules were assembled as nanotubes, and the
      biological recognition of the specific sequence toward Cu lead to efficient Cu
      coating on the nanotubes. Cu nanocrystals were uniformly coated on the histidine
      incorporated nanotubes with high packing density. In addition, the diameter of Cu
      nanocrystal was controlled between 10 and 30 nm on the nanotube by controlling
      the conformation of histidine-rich peptide by means of pH changes. Those
      nanotubes showed significant change in electronic structure by varying the
      nanocrystal diameter; therefore, this system may be developed to a conductivity
      tunable building block for microelectronics and biological sensors. This simple
      biomineralization method can be applied to fabricate various metallic and
      semiconductor nanotubes with peptides whose sequences are known to mineralize
      specific ions.

PMID- 14645718
TI  - Interferon-stimulated transcription and innate antiviral immunity require
      deacetylase activity and histone deacetylase 1.
AB  - The use of histone deacetylase (HDAC) inhibitors has revealed an essential role
      for deacetylation in transcription of IFN-responsive genes. The HDAC1 protein
      associates with both signal transducer and activator of transcription (STAT) 1
      and STAT2, and IFN-alpha stimulation induces deacetylation of histone H4.
      Inhibition of HDAC1 by small interfering RNA (siRNA) decreases IFN-alpha
      responsiveness whereas expression of HDAC1 augments the IFN-alpha response,
      demonstrating that HDAC1 modulates IFN-alpha-induced transcription. Importantly,
      the innate antiviral response is inhibited in the absence of deacetylase
      activity. The requirement for deacetylase is shared by IFN-gamma transcription
      response and may represent a general requirement for STAT-dependent gene
      expression.

PMID- 14645719
TI  - Distinct hyperpolarizing and relaxant roles for gap junctions and endothelium
      derived H2O2 in NO-independent relaxations of rabbit arteries.
AB  - We have compared the contributions of gap junctional communication and chemical
      signaling via H2O2 to NO-independent relaxations evoked by the Ca2+ ionophore
      A23187 and acetylcholine (ACh) in rabbit ilio-femoral arteries. Immunostaining
      confirmed the presence of connexins (Cxs) 37 and 40 in the endothelium and Cxs 40
      and 43 in smooth muscle. Maximal endothelium-dependent subintimal smooth muscle
      hyperpolarizations evoked by A23187 and ACh were equivalent (approximately 20 mV)
      and almost abolished by an inhibitory peptide combination targeted against Cxs
      37, 40, and 43. However, maximal NO-independent relaxations evoked by A23187 were
      unaffected by such peptides, whereas those evoked by ACh were depressed by
      approximately 70%. By contrast, the enzyme catalase, which destroys H2O2,
      attenuated A23187-induced relaxations over a broad range of concentrations, but
      only minimally depressed the maximum response to ACh. Catalase did not affect
      A23187- or ACh-evoked hyperpolarizations. After loading with an H2O2-sensitive
      probe, A23187 caused a marked increase in endothelial fluorescence that
      correlated temporally with relaxation, whereas only a weak delayed increase was
      observed with ACh. In arteries without endothelium, the H2O2-generating system
      xanthine/xanthine oxidase induced a catalase-sensitive relaxation that mimicked
      the gap junction-independent response to A23187 as it was maximally equivalent to
      approximately 80% of induced tone, but associated with a smooth muscle
      hyperpolarization <5 mV. We conclude that myoendothelial gap junctions underpin
      smooth muscle hyperpolarizations evoked by A23187 and ACh, but that A23187
      induced relaxation is dominated by extracellular release of H2O2. Endothelium
      derived H2O2 may thus be regarded as a relaxing factor, but not a hyperpolarizing
      factor, in rabbit arteries.

PMID- 14645720
TI  - Evaluating plague and smallpox as historical selective pressures for the CCR5
      Delta 32 HIV-resistance allele.
AB  - The high frequency, recent origin, and geographic distribution of the CCR5-Delta
      32 deletion allele together indicate that it has been intensely selected in
      Europe. Although the allele confers resistance against HIV-1, HIV has not existed
      in the human population long enough to account for this selective pressure. The
      prevailing hypothesis is that the selective rise of CCR5-Delta 32 to its current
      frequency can be attributed to bubonic plague. By using a population genetic
      framework that takes into account the temporal pattern and age-dependent nature
      of specific diseases, we find that smallpox is more consistent with this
      historical role.

PMID- 14645721
TI  - Map-based isolation of the leaf rust disease resistance gene Lr10 from the
      hexaploid wheat (Triticum aestivum L.) genome.
AB  - More than 50 leaf rust resistance (Lr) genes against the fungal pathogen Puccinia
      triticina have been identified in the wheat gene pool, and a large number of them
      have been extensively used in breeding. Of the 50 Lr genes, all are known only
      from their phenotype and/or map position except for Lr21, which was cloned
      recently. For many years, the problems of molecular work in the large (1.6 x
      10(10) bp), highly repetitive (80%), and hexaploid bread wheat (Triticum aestivum
      L.) genome have hampered map-based cloning. Here, we report the isolation of the
      Lr gene Lr10 from hexaploid wheat by using a combination of subgenome map-based
      cloning and haplotype studies in the genus Triticum. Lr10 is a single-copy gene
      on chromosome 1AS. It encodes a CC-NBS-LRR type of protein with an N-terminal
      domain, which is under diversifying selection. When overexpressed in transgenic
      wheat plants, Lr10 confers enhanced resistance to leaf rust. Lr10 has
      similarities to RPM1 in Arabidopsis thaliana and to resistance gene analogs in
      rice and barley, but is not closely related to other wheat Lr genes based on
      Southern analysis. We conclude that map-based cloning of genes of agronomic
      importance in hexaploid wheat is now feasible, opening perspectives for molecular
      bread wheat improvement trough transgenic strategies and diagnostic allele
      detection.

PMID- 14645722
TI  - A coarse-grained model for a nanometer-scale molecular pump.
AB  - A theory for a nanometer-scale pump based on the ratchet concept is presented. A
      lattice gas model with a set of moves that satisfy hydrodynamic equations is used
      to describe an asymmetric nanometer channel connecting two reservoirs of fluid.
      The channel, which is coupled to an external oscillatory (or stochastic) driving
      force, pumps fluid from one reservoir to the other. The frequency of the external
      driving force, the fluid density, and the channel dimensions are used to control
      the fluid flow. We observe a nonmonotonic behavior of the flow with respect to
      some model parameters and discuss the efficiency of the device.

PMID- 14645723
TI  - Primary inhibition of hypocotyl growth and phototropism depend differently on
      phototropin-mediated increases in cytoplasmic calcium induced by blue light.
AB  - The phototropin photoreceptors transduce blue-light signals into several
      physiological and developmental responses in plants. A transient rise in
      cytoplasmic calcium (Ca2+) that begins within seconds of phototropin 1 (phot1)
      excitation is believed to be an important element in the transduction pathways
      leading to one or more of the phot1-dependent responses. The goal of the present
      work was to determine whether the Ca2+ response was necessary for (a). the
      inhibition of hypocotyl elongation that develops within minutes of the
      irradiation, and (b). hypocotyl phototropism (curved growth of the stem in
      response to asymmetric illumination). After determining that pulses of light
      delivering photon fluences of between 1 and 1000 micromol m-2 induced growth
      inhibition mediated by phot1 without significant interference from other
      photosensory pathways, the effect of blocking the Ca2+ rise was assessed.
      Treatment of seedlings with a Ca2+ chelator prevented the rise in cytoplasmic
      Ca2+ and prevented phot1-mediated growth inhibition. However, the same chelator
      treatment did not impair phot1-mediated phototropism. Thus, it appears that the
      early, transient rise in cytoplasmic Ca2+ is an important intermediary process in
      at least one but not all phot1-signaling pathways.

PMID- 14645724
TI  - Monitoring expression profiles of rice genes under cold, drought, and high
      salinity stresses and abscisic acid application using cDNA microarray and RNA gel
      blot analyses.
AB  - To identify cold-, drought-, high-salinity-, and/or abscisic acid (ABA)-inducible
      genes in rice (Oryza sativa), we prepared a rice cDNA microarray including about
      1700 independent cDNAs derived from cDNA libraries prepared from drought-, cold-,
      and high-salinity-treated rice plants. We confirmed stress-inducible expression
      of the candidate genes selected by microarray analysis using RNA gel-blot
      analysis and finally identified a total of 73 genes as stress inducible including
      58 novel unreported genes in rice. Among them, 36, 62, 57, and 43 genes were
      induced by cold, drought, high salinity, and ABA, respectively. We observed a
      strong association in the expression of stress-responsive genes and found 15
      genes that responded to all four treatments. Venn diagram analysis revealed
      greater cross talk between signaling pathways for drought, ABA, and high-salinity
      stresses than between signaling pathways for cold and ABA stresses or cold and
      high-salinity stresses in rice. The rice genome database search enabled us not
      only to identify possible known cis-acting elements in the promoter regions of
      several stress-inducible genes but also to expect the existence of novel cis
      acting elements involved in stress-responsive gene expression in rice stress
      inducible promoters. Comparative analysis of Arabidopsis and rice showed that
      among the 73 stress-inducible rice genes, 51 already have been reported in
      Arabidopsis with similar function or gene name. Transcriptome analysis revealed
      novel stress-inducible genes, suggesting some differences between Arabidopsis and
      rice in their response to stress.

PMID- 14645725
TI  - Ethylene stimulates endoreduplication but inhibits cytokinesis in cucumber
      hypocotyl epidermis.
AB  - The effects of ethylene on cell division are generally considered inhibitory. In
      this study, we demonstrate that transient ethylene exposure, while suppressing
      cytokinesis, stimulates DNA synthesis. We monitored DNA synthesis and cytokinesis
      in the epidermis of cucumber (Cucumis sativus) hypocotyls, an organ whose post
      germination development involves strictly limited cell division. During exposure
      to ethylene, DNA synthesis, assessed by the incorporation of the thymidine
      homolog 5-bromo-2'-deoxyuridine, was detected in 20% of the epidermal cells,
      whereas DNA synthesis was nearly undetectable in normal air. Cytofluorometric
      analysis of nuclei in affected cells showed an up to 8-fold increase in DNA
      content. During this time, new cell plate formation was not detected. However,
      shortly after ethylene was removed, DNA content was rapidly restored to 2C
      (diploid) levels in all cells, and new cell plate formation dramatically
      increased. These results demonstrate that ethylene promotes DNA synthesis and its
      endoreduplication but inhibits cytokinesis, thereby maintaining some cells in G2
      phase.

PMID- 14645726
TI  - Decreased content of leaf ferredoxin changes electron distribution and limits
      photosynthesis in transgenic potato plants.
AB  - A complete ferredoxin (Fd) cDNA clone was isolated from potato (Solanum tuberosum
      L. cv Desiree) leaves. By molecular and immunoblot analysis, the gene was
      identified as the leaf-specific Fd isoform I. Transgenic potato plants were
      constructed by introducing the homologous potato fed 1 cDNA clone as an antisense
      construct under the control of the constitutive cauliflower mosaic virus 35S
      promoter. Stable antisense lines with Fd contents between 40% and 80% of the wild
      type level were selected by northern- and western-blot analysis. In short-term
      experiments, the distribution of electrons toward their stromal acceptors was
      altered in the mutant plants. Cyclic electron transport, as determined by the
      quantum yields of photosystems I and II, was enhanced. The CO2 assimilation rate
      was decreased, but depending on the remaining Fd content, some lines showed
      photoinhibition. The leaf protein content remained largely constant, but the
      antisense plants had a lower total chlorophyll content per unit leaf area and an
      increased chlorophyll a/b ratio. In the antisense plants, the redox state of the
      quinone acceptor A in photosystem II (QA) was more reduced than that of the wild
      type plants under all experimental conditions. Because the plants with lower Fd
      amounts reacted as if they were grown under a higher light intensity, the
      possibility that the altered chloroplast redox state affects light acclimation is
      discussed.

PMID- 14645727
TI  - T-DNA integration in Arabidopsis chromosomes. Presence and origin of filler DNA
      sequences.
AB  - To investigate the relationship between T-DNA integration and double-stranded
      break (DSB) repair in Arabidopsis, we studied 67 T-DNA/plant DNA junctions and 13
      T-DNA/T-DNA junctions derived from transgenic plants. Three different types of T
      DNA-associated joining could be distinguished. A minority of T-DNA/plant DNA
      junctions were joined by a simple ligation-like mechanism, resulting in a
      junction without microhomology or filler DNA insertions. For about one-half of
      all analyzed junctions, joining of the two ends occurred without insertion of
      filler sequences. For these junctions, microhomology was strikingly combined with
      deletions of the T-DNA ends. For the remaining plant DNA/T-DNA junctions, up to
      51-bp-long filler sequences were present between plant DNA and T-DNA contiguous
      sequences. These filler segments are built from several short sequence motifs,
      identical to sequence blocks that occur in the T-DNA ends and/or the plant DNA
      close to the integration site. Mutual microhomologies among the sequence motifs
      that constitute a filler segment were frequently observed. When T-DNA integration
      and DSB repair were compared, the most conspicuous difference was the frequency
      and the structural organization of the filler insertions. In Arabidopsis, no
      filler insertions were found at DSB repair junctions. In maize (Zea mays) and
      tobacco (Nicotiana tabacum), DSB repair-associated filler was normally composed
      of simple, uninterrupted sequence blocks. Thus, although DSB repair and T-DNA
      integration are probably closely related, both mechanisms have some exclusive and
      specific characteristics.

PMID- 14645728
TI  - LAF3, a novel factor required for normal phytochrome A signaling.
AB  - Phytochrome A (phyA) is the photolabile plant light receptor that mediates broad
      spectrum very low-fluence responses and high irradiance responses to continuous
      far-red light (FRc). An Arabidopsis mutant laf3-1 (long after far-red 3) was
      recovered from a screen for transposon-tagged mutants that exhibit reduced
      inhibition of hypocotyl elongation in FRc. The laf phenotype correlated well with
      a strongly attenuated disappearance of XTR7 transcript in FRc. The effects of
      laf3-1 on phyA-controlled CAB, CHS, and PET H expression were more subtle, and
      the mutation had no clear effects on PET E and ASN1 transcript levels in FRc. The
      use of two alternative transcription initiation sites in the LAF3 gene generates
      two isoforms that differ only at their N termini. Transcripts encoding both
      isoforms were induced during germination and were present at slightly higher
      levels in de-etiolated seedlings than in those grown in darkness. No significant
      differential regulation of the two isoforms was observed upon exposure to either
      FRc or continuous red light. Transcripts encoding the shorter isoform (LAF3ISF2)
      always appear to be more abundant than those encoding the longer isoform
      (LAF3ISF1). However, both isoforms were capable of full complementation of the
      laf3-1 hypocotyl phenotype in FRc. When fused to a yellow fluorescent protein,
      both isoforms localize to the perinuclear region, suggesting that LAF3 encodes a
      product that might regulate nucleo-cytoplasmic trafficking of an intermediate(s)
      involved in phyA signal transduction.

PMID- 14645729
TI  - Photomorphogenic responses in maize seedling development.
AB  - As an emerging maize (Zea mays) seedling senses light, there is a decrease in the
      rate of mesocotyl elongation, an induction of root growth, and an expansion of
      leaves. In leaf tissues, mesophyll and bundle sheath cell fate is determined, and
      the proplastids of each differentiate into the dimorphic chloroplasts typical of
      each cell type. Although it has been inferred from recent studies in several
      model plant species that multiple photoreceptor systems mediate this process,
      surprisingly little is known of light signal transduction in maize. Here, we
      examine two photomorphogenic responses in maize: inhibition of mesocotyl
      elongation and C4 photosynthetic differentiation. Through an extensive survey of
      white, red, far-red, and blue light responses among a diverse collection of
      germplasm, including a phytochrome-deficient mutant elm1, we show that light
      response is a highly variable trait in maize. Although all inbreds examined
      appear to have a functional phytochrome signal transduction pathway, several
      lines showed reduced sensitivity to blue light. A significant correlation was
      observed between light response and subpopulation, suggesting that light
      responsiveness may be a target of artificial selection. An examination of C4 gene
      expression patterns under various light regimes in the standard W22 inbred and
      elm1 indicate that cell-specific patterns of C4 gene expression are maintained in
      fully differentiated tissues independent of light quality. To our knowledge,
      these findings represent the first comprehensive survey of light response in
      maize and are discussed in relation to maize breeding strategies.

PMID- 14645730
TI  - Inorganic carbon limitation induces transcripts encoding components of the CO(2)
      concentrating mechanism in Synechococcus sp. PCC7942 through a redox-independent
      pathway.
AB  - The cyanobacterial CO2-concentrating mechanism (CCM) allows photosynthesis to
      proceed in CO2-limited aquatic environments, and its activity is modulated in
      response to inorganic carbon (Ci) availability. Real-time reverse transcriptase
      PCR analysis was used to examine the transcriptional regulation of more than 30
      CCM-related genes in Synechococcus sp. strain PCC7942 with an emphasis on genes
      encoding high-affinity Ci transporters and carboxysome-associated proteins. This
      approach was also used to test hypotheses about sensing of Ci limitation in
      cyanobacteria. The transcriptional response of Synechococcus sp. to severe Ci
      limitation occurs rapidly, being maximal within 30 to 60 min, and three distinct
      temporal responses were detected: (a). a rapid, transient induction for genes
      encoding carboxysome-associated proteins (ccmKLMNO, rbcLS, and icfA) and the
      transcriptional regulator, cmpR; (b). a slow sustained induction of psbAII; and
      (c). a rapid sustained induction of genes encoding the inducible Ci transporters
      cmpABCD, sbtA, and ndhF3-D3-chpY. The Ci-responsive transcripts investigated had
      half-lives of 15 min or less and were equally stable at high and low Ci. Through
      the use of a range of physiological conditions (light and Ci levels) and
      inhibitors such as 3-(3,4-dichlorophenyl)-1,1dimethylurea, glycolaldehyde,
      dithiothreitol, and ethoxyzolamide, we found that no strict correlation exists
      between expression of genes known to be induced under redox stress, such as
      psbAII, and the expression of the Ci-responsive CCM genes. We argue that redox
      stress, such as that which occurs under high-light stress, is unlikely to be a
      primary signal for sensing of Ci limitation in cyanobacteria. We discuss the data
      in relation to current theories of CO2 sensing in cyanobacteria.

PMID- 14645731
TI  - Overexpression of a mutant basic helix-loop-helix protein HFR1, HFR1-deltaN105,
      activates a branch pathway of light signaling in Arabidopsis.
AB  - The HFR1, a basic helix-loop-helix protein, is required for a subset of
      phytochrome A-mediated photoresponses in Arabidopsis. Here, we show that
      overexpression of the HFR1-deltaN105 mutant, which lacks the N-terminal 105 amino
      acids, confers exaggerated photoresponses even in darkness. Physiological
      analysis implied that overexpression of HFR1-deltaN105 activated constitutively a
      branch pathway of light signaling that mediates a subset of photomorphogenic
      responses, including germination, de-etiolation, gravitropic hypocotyl growth,
      blocking of greening, and expression of some light-regulated genes such as CAB,
      DRT112, PSAE, PSBL, PORA, and XTR7, without affecting the light-responsiveness of
      anthocyanin accumulation and expression of other light-regulated genes such as
      CHS and PSBS. Although the end-of-day far-red light response and petiole
      elongation were suppressed in the HFR1-deltaN105-overexpressing plants, flowering
      time was not affected by HFR1-deltaN105. In addition, the HFR1-deltaN105
      overexpressing plants showed hypersensitive photoresponses in the inhibition of
      hypocotyl elongation, dependently on phytochrome A, FHY1, and FHY3 under FR light
      or phyB under R light, respectively. Moreover, our double mutant analysis
      suggested that the hypersensitive photoresponse is due to functional cooperation
      between HFR1-deltaN105 and other light-signaling components including HY5, a
      basic leucine zipper protein. Taken together, our results of gain-of-function
      approach with HFR1-deltaN105 suggest the existence of a complex and important
      basic helix-loop-helix protein-mediated transcriptional network controlling a
      branch pathway of light signaling and provide a useful framework for further
      genetic dissection of light-signaling network in Arabidopsis.

PMID- 14645732
TI  - The fasciclin-like arabinogalactan proteins of Arabidopsis. A multigene family of
      putative cell adhesion molecules.
AB  - Fasciclin-like arabinogalactan proteins (FLAs) are a subclass of arabinogalactan
      proteins (AGPs) that have, in addition to predicted AGP-like glycosylated
      regions, putative cell adhesion domains known as fasciclin domains. In other
      eukaryotes (e.g. fruitfly [Drosophila melanogaster] and humans [Homo sapiens]),
      fasciclin domain-containing proteins are involved in cell adhesion. There are at
      least 21 FLAs in the annotated Arabidopsis genome. Despite the deduced proteins
      having low overall similarity, sequence analysis of the fasciclin domains in
      Arabidopsis FLAs identified two highly conserved regions that define this motif,
      suggesting that the cell adhesion function is conserved. We show that FLAs
      precipitate with beta-glucosyl Yariv reagent, indicating that they share
      structural characteristics with AGPs. Fourteen of the FLA family members are
      predicted to be C-terminally substituted with a glycosylphosphatidylinositol
      anchor, a cleavable form of membrane anchor for proteins, indicating different
      FLAs may have different developmental roles. Publicly available microarray and
      expressed sequence tag data were used to select FLAs for further expression
      analysis. RNA gel blots for a number of FLAs indicate that they are likely to be
      important during plant development and in response to abiotic stress. FLAs 1,2,
      and 8 show a rapid decrease in mRNA abundance in response to the phytohormone
      abscisic acid. Also, the accumulation of FLA1 and FLA2 transcripts differs during
      callus and shoot development, indicating that the proteins may be significant in
      the process of competence acquisition and induction of shoot development.

PMID- 14645733
TI  - Lipid storage metabolism is limited by the prevailing low oxygen concentrations
      within developing seeds of oilseed rape.
AB  - The aim of this study was to investigate whether endogenous restrictions in
      oxygen supply are limiting for storage metabolism in developing oilseed rape
      (Brassica napus) seeds. Siliques were studied 30 d after flowering, when rapid
      lipid accumulation is occurring in the seeds. (a). By using microsensors, oxygen
      concentrations were measured within seeds and in the silique space between seeds.
      At ambient external oxygen (21% [v/v]) in the light, oxygen fell to 17% (v/v)
      between and 0.8% (v/v) within seeds. A step-wise reduction of the external oxygen
      concentration led within 2 h to a further decrease of internal oxygen
      concentrations, and a step-wise increase of the external oxygen concentration up
      to 60% (v/v) resulted in an increase in internal oxygen that rose to 30% (v/v)
      between and 8% (v/v) within seeds. (b). The increase in oxygen levels in the
      seeds was accompanied by a progressive increase in the levels of ATP, UTP, and
      the ATP to ADP and UTP to UDP ratios over the entire range from 0% to 60% (v/v)
      external oxygen. (c). To investigate metabolic fluxes in planta, 14C-sucrose was
      injected into seeds, which remained otherwise intact within their siliques. The
      increase in oxygen in the seeds was accompanied by a progressive increase in the
      rate of lipid (including triacylglycerol), protein and cell wall synthesis, and
      an increase in glycolytic flux over a range from sub- to superambient oxygen
      concentrations. In contrast to lipid synthesis, starch synthesis was not
      significantly increased at superambient oxygen levels. The levels of fermentation
      products such as lactate and glycerol-3P increased only at very low (0%-4% [v/v])
      external oxygen concentrations. (d). When 14C-acetate or 14C-acetyl-coenzyme A
      (CoA) was injected into seeds, label incorporation into triacylglycerol
      progressively increased over the whole range of external oxygen concentrations
      from 0% to 60% (v/v). (e). Stimulation of lipid synthesis was accompanied by an
      increase in sugar levels and a decrease in the levels of hexose-phosphates and
      acetyl-CoA, indicating sucrose unloading and the use of acetyl-CoA as possible
      regulatory sites. (f). Increased lipid synthesis was also accompanied by an
      increase in the maximal activities of invertase and diacylglycerol
      acyltransferase. (g). The developmental shift from starch to lipid storage
      between 15 and 45 d after flowering was accompanied by an increase in the seed
      energy state. (h). The results show that at ambient oxygen levels, the oxygen
      supply is strongly limiting for energy metabolism and biosynthetic fluxes in
      growing rape seeds, affecting lipid synthesis more strongly than starch
      synthesis. The underlying mechanisms and implications for strategies to increase
      yield and storage product composition in oilseed crops are discussed.

PMID- 14645734
TI  - A genomic analysis of the shade avoidance response in Arabidopsis.
AB  - Plants respond to the proximity of neighboring vegetation by elongating to
      prevent shading. Red-depleted light reflected from neighboring vegetation
      triggers a shade avoidance response leading to a dramatic change in plant
      architecture. These changes in light quality are detected by the phytochrome
      family of photoreceptors. We analyzed global changes in gene expression over time
      in wild-type, phyB mutant, and phyA phyB double mutant seedlings of Arabidopsis
      in response to simulated shade. Using pattern fitting software, we identified 301
      genes as shade responsive with patterns of expression corresponding to one of
      various physiological response modes. A requirement for a consistent pattern of
      expression across 12 chips in this way allowed more subtle changes in gene
      expression to be considered meaningful. A number of previously characterized
      genes involved in light and hormone signaling were identified as shade
      responsive, as well as several putative, novel shade-specific signal transduction
      factors. In addition, changes in expression of genes in a range of pathways
      associated with elongation growth and stress responses were observed. The
      majority of shade-responsive genes demonstrated antagonistic regulation by phyA
      and phyB in response to shade following the pattern of many physiological
      responses. An analysis of promoter elements of genes regulated in this way
      identified conserved promoter motifs potentially important in shade regulation.

PMID- 14645735
TI  - Genomic characterization and expression analysis of the first nonmammalian renin
      genes from zebrafish and pufferfish.
AB  - Renin is a key enzyme in the renin-angiotensin system (RAS), a pathway which
      plays an important physiological role in blood pressure and electrolyte
      homeostasis. The origin of the RAS is believed to have accompanied early
      evolution of vertebrates. However, renin genes have so far only been
      unequivocally identified in mammals. Whether or not a bona fide renin gene exists
      in nonmammalian vertebrates has been an intriguing question of physiological and
      evolutionary interest. Using a genomic analytical approach, we identified renin
      genes in two nonmammalian vertebrates, zebrafish (Danio rerio) and pufferfish
      (Takifugu rubripes). Phylogenetic analysis demonstrates that the predicted fish
      renins cluster together with mammalian renins to form a distinct subclass of
      vertebrate aspartyl proteases. RT-PCR results confirm generation of the predicted
      zebrafish mRNA and its expression in association with the opisthonephric kidney
      of adult zebrafish. Comparative in situ hybridization analysis of wild-type and
      developmental mutants indicates that renin expression is first detected
      bilaterally in cells of the interrenal primordia at 24 h postfertilization, which
      subsequently migrate to lie adjacent to, but distinct from, the glomerulus of the
      developing pronephric kidney. Our report provides the first molecular evidence
      for the existence of renin genes in lower vertebrates. The observation that the
      earliest renin-expressing cells, arising during ontogeny of this teleost
      vertebrate, are of adrenocortical lineage raises an interesting hypothesis as
      regards the origin of renin-expressing cells in the metanephric kidney of higher
      vertebrates.

PMID- 14645736
TI  - A comparison of oligonucleotide and cDNA-based microarray systems.
AB  - Large-scale public data mining will become more common as public release of
      microarray data sets becomes a corequisite for publication. Therefore, there is
      an urgent need to clarify whether data from different microarray platforms are
      comparable. To assess the compatibility of microarray data, results were compared
      from the two main types of high-throughput microarray expression technologies,
      namely, an oligonucleotide-based and a cDNA-based platform, using RNA obtained
      from complex tissue (human colonic mucosa) of five individuals. From 715 sequence
      verified genes represented on both platforms, 64% of the genes matched in
      "present" or "absent" calls made by both platforms. Calls were influenced by
      spurious signals caused by Alu repeats in cDNA clones, clone annotation errors,
      or matched probes that were designed to different regions of the gene; however,
      these factors could not completely account for the level of call discordance
      observed. Expression levels in sequence-verified, platform-overlapping genes were
      not related, as demonstrated by weakly positive rank order correlation. This
      study demonstrates that there is only moderate overlap in the results from the
      two array systems. This fact should be carefully considered when performing large
      scale analyses on data originating from different microarray platforms.

PMID- 14645737
TI  - Molecular signature of late-stage human ALS revealed by expression profiling of
      postmortem spinal cord gray matter.
AB  - Little is known about global gene expression patterns in the human
      neurodegenerative disease amyotrophic lateral sclerosis (ALS). To address this,
      we used high-density oligonucleotide microarray technology to compare expression
      levels of approximately 6,800 genes in postmortem spinal cord gray matter
      obtained from individuals with ALS as well as normal individuals. Using Fisher
      discriminant analysis (FDA) and leave-one-out cross-validation (LOOCV), we
      discerned an ALS-specific signature. Moreover, it was possible to distinguish
      familial ALS (FALS) from sporadic ALS (SALS) gene expression profiles.
      Characterization of the specific genes significantly altered in ALS uncovered a
      pro-inflammatory terminal state. Moreover, we found alterations in genes involved
      in mitochondrial function, oxidative stress, excitotoxicity, apoptosis,
      cytoskeletal architecture, RNA transcription and translation, proteasomal
      function, and growth and signaling. It is apparent from this study that DNA
      microarray analysis and appropriate bioinformatics can reveal distinct phenotypic
      changes that underlie the terminal stages of neurodegeneration in ALS.

PMID- 14645738
TI  - Altered mRNA abundance of ASB15 and four other genes in skeletal muscle following
      administration of beta-adrenergic receptor agonists.
AB  - Beta-adrenergic receptor agonists (BA) stimulate skeletal muscle growth. However,
      downstream signaling pathways that facilitate this effect remain poorly defined.
      Objectives of this study were to identify genes differentially expressed after
      administration of a novel BA and to evaluate the expression of one of those genes
      in additional models of skeletal muscle growth. Differentially expressed gene
      fragments were identified through differential display of skeletal muscle
      biopsies from five steers 24 h after administration of the BA. Five gene
      fragments designated DD53, DD143, DD163, DD209, and DD214 were identified. Tissue
      distribution of these genes was evaluated by RT-PCR. While DD53, DD163, DD209,
      and DD214 were expressed across tissues, DD143 mRNA expression was most abundant
      in skeletal muscle. DD143, later identified as bovine ASB15, was evaluated in
      rats following administration of anabolic compounds. Thirteen 7-wk-old female
      rats were randomly assigned to each of four treatment groups including: control,
      clenbuterol, trenbolone acetate (TBA), and growth hormone (GH). Changes in rat
      Asb-15 mRNA were measured at 30 min, 12 h, and 24 h following intraperitoneal
      injections of each compound. Clenbuterol treatment decreased Asb-15 mRNA in
      skeletal muscle at 12 and 24 h (P < 0.01) and also decreased mRNA in lung at 12 h
      (P < 0.05). TBA and GH treatments did not alter Asb-15 mRNA in any of the tissues
      evaluated (P > 0.10). These results are the first to associate an Asb gene family
      member with muscle growth or BA administration and suggest a potential role for
      ASB15 in beta-agonist-induced skeletal muscle hypertrophy.

PMID- 14645739
TI  - Working differently for better, safer care.

PMID- 14645740
TI  - Improvement, trust, and the healthcare workforce.
AB  - Although major defects in the performance of healthcare systems are well
      documented, progress toward remedy remains slow. Accelerating improvement will
      require large shifts in attitudes toward and strategies for developing the
      healthcare workforce. At present, prevailing strategies rely largely on outmoded
      theories of control and standardisation of work. More modern, and much more
      effective, theories of production seek to harness the imagination and
      participation of the workforce in reinventing the system. This requires a
      workforce capable of setting bold aims, measuring progress, finding alternative
      designs for the work itself, and testing changes rapidly and informatively. It
      also requires a high degree of trust in many forms, a bias toward teamwork, and a
      predilection toward shouldering the burden of improvement, rather than blaming
      external factors. A new healthcare workforce strategy, founded on these
      principles, will yield much faster improvement than at present.

PMID- 14645741
TI  - Applying the lessons of high risk industries to health care.
AB  - High risk industries such as commercial aviation and the oil and gas industry
      have achieved exemplary safety performance. This paper reviews how they have
      managed to do that. The primary reasons are the positive attitudes towards safety
      and the operation of effective formal safety management systems. The safety
      culture provides an important explanation of why such organisations perform well.
      An evolutionary model of safety culture is provided in which there is a range of
      cultures from the pathological through the reactive to the calculative. Later,
      the proactive culture can evolve towards the generative organisation, an
      alternative description of the high reliability organisation. The current status
      of health care is reviewed, arguing that it has a much higher level of accidents
      and has a reactive culture, lagging behind both high risk industries studied in
      both attitude and systematic management of patient risks.

PMID- 14645742
TI  - Quality care means valuing care assistants, porters, and cleaners too.
AB  - All too often, the focus of the very clever strategy papers produced in the upper
      reaches of the health department is on the next grand plan. Some of these reforms
      have been catastrophic for the quality of service that patients experience at
      ward level. Of these, the contracting out culture introduced in the 1980s and the
      1990s has been the worst. Researching my book, Hard work-life in low pay Britain,
      I took six jobs at around the minimum wage, including work as a hospital porter,
      as a hospital cleaner, and as a care assistant. These are jobs at the sharp end,
      up close and very personal to the patients, strongly influencing their
      experiences of the services they were using. Yet they are low paid, undervalued
      jobs that fall below the radar of the policy makers. In hospitals they need to be
      brought back in-house and integrated into a team ethos. Paying these people more
      would cost more, but it would also harvest great rewards by using their untapped
      commitment.

PMID- 14645743
TI  - Can we select health professionals who provide safer care.
AB  - In order to improve patient safety, health services are looking to other
      industries' experiences and as a result are adopting a systems approach to
      learning from error, rather than simply focusing the blame on the individual.
      However, in health care the individual will remain an important contributor to
      safety and this paper looks at other literatures besides health to consider a
      number of individual characteristics and the role they might play in terms of
      work practices that affect patient safety. It considers the effects of a variety
      of personality profiles including sensation seeking, Type A, and those with high
      self esteem; looks at our ability to select for psychological wellbeing; and
      discusses the ways that psychometrics have been used in medicine to predict
      performance. It concludes that although rarely used, psychometrics has been shown
      to be useful in predicting some aspects of performance in medicine and suggests
      that this is an area well worth further study for the benefit of patient care.
      Nevertheless, we are a long way away from being able to select safer staff and
      should instead be developing this knowledge to enable us to recognise and address
      potential difficulties.

PMID- 14645744
TI  - Doctors and managers: poor relationships may be damaging patients-what can be
      done?
AB  - The problem of poor relationships between doctors and managers is a common
      feature of many healthcare systems. This problem needs to be explicitly addressed
      and there are a number of positive steps that could be taken. Firstly, there
      would be value in working to improve the quality of relationships and better
      mutual understanding of the necessarily different positions of doctors and
      managers. Finding a common approach to managing resources, accountability,
      autonomy, and the creation of more systematic ways of working seems to be
      important. The use of costed clinical pathways may be one approach. Rather than
      seeing guidelines and accountability systems as a threat to autonomy there is an
      argument that they are an essential adjunct to it. Redefining autonomy in order
      to preserve it and to ensure that it encompasses accountability and
      responsibility will be an important step. A key step is the development of
      clinical leadership.

PMID- 14645745
TI  - Multidisciplinary team working, clinical networks, and chambers; opportunities to
      work differently in the NHS.
AB  - Recently in the United Kingdom some new organisational structures for clinicians
      have been discussed. So far little has changed, but the intensity of interest
      suggests this may be an opportunity to link change in working practices with
      improvements in quality. Multidisciplinary team working is developing within the
      National Health Service (NHS) and some groups are expanding their roles across
      traditional institutional boundaries to form complex clinical networks. It would
      require little to make these functional networks autonomous from current NHS
      structures. Other models of working without traditional institutional boundaries
      have been discussed, including the formation of "chambers" for doctors and other
      professionals. We describe the first tentative steps of one group as an example
      and suggest that further experimentation with evaluation is required.

PMID- 14645746
TI  - Reducing prescribing error: competence, control, and culture.
AB  - Medication errors are probably the most prevalent form of medical error, and
      prescribing errors are the most important source of medication errors. In this
      article we suggest interventions are needed at three levels to improve
      prescribing: (1) improve the training, and test the competence, of prescribers;
      (2) control the environment in which prescribers perform in order to standardise
      it, have greater controls on riskier drugs, and use technology to provide
      decision support; and (3) change organisational cultures, which do not support
      the belief that prescribing is a complex, technical, act, and that it is
      important to get it right. Solutions involve overt acknowledgement of this by
      senior clinicians and managers, and an open process of sharing and reviewing
      prescribing decisions.

PMID- 14645747
TI  - "Doing prescribing": how might clinicians work differently for better, safer
      care.
AB  - Prescribing medicines is a cornerstone of medical practice. There is, however,
      ample evidence that the prescribing process is far from ideal when viewed from
      the perspective of patients who wish to understand why they should take medicine,
      what potential harm they might face, and how they might integrate medicine taking
      into the pattern of their life, beliefs, and attitudes. Misalignment between
      clinicians and patients about medicine taking leads to a multitude of problems.
      Recently, a concept known as concordance has been suggested, where the
      prescribing interaction is seen as a process where both the patient and
      professional views and beliefs about medication, and the associated harms and
      benefits, are shared and negotiated. This interaction depends on a communication
      process that is becoming known as shared decision making between clinicians and
      patients. Although there is as yet little evidence that this approach leads to
      improved clinical outcomes, ethical principles and the core values of medical
      practice suggest that involving patients in the prescribing process will lead to
      better, safer care.

PMID- 14645748
TI  - Rewarding results: using financial incentives to improve quality.

PMID- 14645749
TI  - A crisis in maternity services: the courage to be wrong.

PMID- 14645750
TI  - Evaluating the culture of safety.

PMID- 14645751
TI  - Reviewing case record review.

PMID- 14645752
TI  - User responsiveness in health care.

PMID- 14645753
TI  - Classifying and identifying errors.

PMID- 14645754
TI  - Evaluation of the culture of safety: survey of clinicians and managers in an
      academic medical center.
AB  - BACKGROUND: Despite the emphasis on patient safety in health care, few
      organizations have evaluated the extent to which safety is a strategic priority
      or their culture supports patient safety. In response to the Institute of
      Medicine's report and to an organizational commitment to patient safety, we
      conducted a systematic assessment of safety at the Johns Hopkins Hospital (JHH)
      and, from this, developed a strategic plan to improve safety. The specific aims
      of this study were to evaluate the extent to which the culture supports patient
      safety at JHH and the extent to which safety is a strategic priority. METHODS:
      During July and August 2001 we implemented two surveys in disparate populations
      to assess patient safety. The Safety Climate Scale (SCS) was administered to a
      sample of physicians, nurses, pharmacists, and other ICU staff. SCS assesses
      perceptions of a strong and proactive organizational commitment to patient
      safety. The second survey instrument, called Strategies for Leadership (SLS),
      evaluated the extent to which safety was a strategic priority for the
      organization. This survey was administered to clinical and administrative
      leaders. RESULTS: We received 395 completed SCS surveys from 82% of the
      departments and 86% of the nursing units. Staff perceived that supervisors had a
      greater commitment to safety than senior leaders. Nurses had higher scores than
      physicians for perceptions of safety. Twenty three completed SLS surveys were
      received from 77% of the JHH Patient Safety Committee members and 50% of the JHH
      Management Committee members. Management Committee responses were more positive
      than Patient Safety Committee, indicating that management perceived safety
      efforts to be further developed. Strategic planning received the lowest scores
      from both committees. CONCLUSIONS: We believe this is one of the first large
      scale efforts to measure institutional culture of safety and then design
      improvements in health care. The survey results suggest that strategic planning
      of patient safety needs enhancement. Several efforts to improve our culture of
      safety were initiated based on these results, which should lead to measurable
      improvements in patient safety.

PMID- 14645755
TI  - Case record review of adverse events: a new approach.
AB  - OBJECTIVES: To redesign the existing clinical review form (RF2) used in previous
      retrospective case record review studies in order to clarify the review process
      and provide a more powerful analysis of adverse events; and then to ask
      clinicians to pilot and evaluate the new modular review form (MRF2). The review
      form is divided into five sections, each with a defined purpose, providing a
      modular structure. DESIGN: Design and testing of the MRF2 on a sample of medical
      and nursing records, and evaluation of the reviewers' responses regarding the new
      review form. SETTING: Hospital based teams from eight countries. RESULTS: The
      modular review form was reported to be comprehensive, well structured, and clear.
      Most of the reviewers agreed with the positive statements regarding the review
      form. Overall, the modular structure was thought to be helpful. Several
      modifications have been made to the final version to take account of criticisms
      and suggestions. CONCLUSIONS: The full potential of case record review has yet to
      be explored. The benefits of this review form include a modular format which
      enables reviewers or project leaders to select the focus of their review based on
      resources and the purpose of the review, and to identify contributory factors
      which indicate areas for improvement and prevention. The training of reviewers is
      of vital importance for record review. Record review remains one of the primary
      methods for assessing the incidence of adverse events and the new format is
      suitable for both prospective and retrospective review.

PMID- 14645756
TI  - A pilot study in ophthalmology of inter-rater reliability in classifying
      diagnostic errors: an underinvestigated area of medical error.
AB  - BACKGROUND: Misdiagnosis is the least studied form of medical error. Before
      effective strategies to reduce misdiagnosis can be developed, there needs to be a
      better understanding of the factors that lead to these errors. AIM: To evaluate
      the applicability and reliability of three classification systems for
      misdiagnosis. DESIGN: Retrospective independent analysis of five cases by
      clinical experts. PARTICIPANTS: Three ophthalmologists trained in ocular oncology
      who devote at least 75% of their practice to ocular oncology. MAIN OUTCOME
      MEASURES: Percentage agreement in determining cause of misdiagnosis. RESULTS:
      Participants agreed a misdiagnosis occurred in all cases and the error was graded
      as serious 14 of 15 times (93%). Inter-rater agreement for root cause varied
      among the three classification systems from 47% to zero. CONCLUSIONS: Although
      there was excellent agreement among clinical experts of what constitutes serious
      misdiagnosis under idealized conditions, there is not a reliable method for
      categorizing the primary or root cause for these errors. The origins of
      misdiagnosis are complex, often multifactorial, and more difficult to categorize
      than other types of medical error. Misdiagnosis is a professional and public
      healthcare challenge that will require novel strategies to enable it to be
      successfully studied.

PMID- 14645757
TI  - Assessing the quality of care of multiple conditions in general practice:
      practical and methodological problems.
AB  - OBJECTIVE: To investigate practical and methodological problems in assessing the
      quality of care of multiple conditions in general practice. SETTING: Sixteen
      general practices from two socioeconomically diverse regions in the UK. METHOD:
      Quality of care was assessed in 100 randomly selected patient records in each
      practice using an established set of quality indicators covering 23 conditions
      commonly seen in primary care. Inter-rater reliability assessment was carried out
      for five of the conditions. RESULTS: Conducting simultaneous quality assessment
      across multiple conditions is highly resource intensive. Poor data quality and
      the low prevalence of some items of care defined by the indicators are
      significant problems. Scores for individual indicators require very large samples
      for reliable assessment. Quality scores are more reliable when reported at a
      higher unit of analysis. This is particularly true for indicators and conditions
      with low prevalence where data may need to be aggregated to the level of groups
      of conditions or organisational providers. There is no single ideal way of
      aggregating quality scores. CONCLUSION: The study identified some of the
      practical and methodological difficulties in assessing quality of care across
      multiple conditions. For improved quality assessment, advances in information
      technology and improvements in data quality are required for more efficient and
      reliable data extraction from medical records, together with the development of
      methods for combining scores across indicators, conditions, and practices.
      However, electronic data extraction methods will still be based on the assumption
      that the care recorded reflects the care provided.

PMID- 14645758
TI  - Is the methodological quality of guidelines declining in the US? Comparison of
      the quality of US Agency for Health Care Policy and Research (AHCPR) guidelines
      with those published subsequently.
AB  - OBJECTIVE: To determine whether North American guidelines published subsequent to
      and in the same topic areas as those developed by the US Agency for Health Care
      Policy and Research (AHCPR) meet the same methodological criteria. STUDY DESIGN:
      A guideline appraisal instrument containing 30 criteria was used to evaluate the
      methodological quality of the AHCPR guidelines, "updates" of the AHCPR guidelines
      authored by others, and guidelines that referenced or were adapted from the AHCPR
      guidelines. The frequency with which the criteria appeared in each guideline was
      compared and an analysis was performed to determine guidelines with two key
      features of the ACHPR guidelines-multidisciplinary guideline development panels
      and systematic reviews of the literature. Data were extracted from the guidelines
      by one investigator and then checked for accuracy by the other. RESULTS: Fifty
      two guidelines identified by broad based searches were evaluated. 50% of the
      criteria were present in every AHCPR guideline. The AHCPR guidelines scored 80%
      or more on 24 of the 30 criteria compared with 14 for the "updates" and 11 for
      those that referenced/adapted the AHCPR guidelines. All of the 17 AHCPR
      guidelines had both multidisciplinary development panels and systematic reviews
      of the literature compared with five from the other two categories (p<0.05).
      CONCLUSIONS: North American guidelines developed subsequent to and in the same
      topic areas as the AHCPR guidelines are of substantially worse methodological
      quality and ignore key features important to guideline development. This finding
      contrasts with previously published conclusions that guideline methodological
      quality is improving over time.

PMID- 14645759
TI  - Public opinion on systems for feeding back views to the National Health Service.
AB  - OBJECTIVES: To explore public opinions about different systems for feeding back
      views about health services to the National Health Service. DESIGN: Questionnaire
      survey. SETTING: NHS Grampian, Scotland, UK. PARTICIPANTS: A random sample of 10
      000 adults registered with a general practitioner in Grampian was invited to opt
      in to the study; 2449 were sent questionnaires. OUTCOME MEASURES: Opinions about
      different feedback mechanisms and their likely effectiveness in three scenarios;
      reasons for preferring particular mechanisms. RESULTS: Of 1951 respondents, over
      80% thought patient representatives would be a good way for people to pass on
      their ideas about the NHS and would help to improve it. Patient representatives
      were the most widely preferred course of action for two out of three scenarios.
      People explained their preferences for particular feedback systems mainly in
      terms of their ease of use, the perception that they would be listened to, and
      the likelihood of anything being done about what they said. However, people
      varied in their judgements about the likely effectiveness of different feedback
      systems. Preferences for particular systems varied according to the types of
      situation considered. Some people are reluctant to approach clinical staff with
      concerns about healthcare quality. A substantial minority have no confidence that
      their concerns would be listened to or acted upon, however they were expressed.
      CONCLUSION: The "patient representative" function has substantial popular support
      and could facilitate local learning and action to improve the quality of health
      services from users' perspectives. Feedback systems must demonstrate their
      effectiveness if they are to gain and retain public confidence.

PMID- 14645760
TI  - Errors in general practice: development of an error classification and pilot
      study of a method for detecting errors.
AB  - OBJECTIVE: To describe a classification of errors and to assess the feasibility
      and acceptability of a method for recording staff reported errors in general
      practice. DESIGN: An iterative process in a pilot practice was used to develop a
      classification of errors. This was incorporated in an anonymous self-report form
      which was then used to collect information on errors during June 2002. The
      acceptability of the reporting process was assessed using a self-completion
      questionnaire. SETTING: UK general practice. PARTICIPANTS: Ten general practices
      in the North East of England. MAIN OUTCOME MEASURES: Classification of errors,
      frequency of errors, error rates per 1000 appointments, acceptability of the
      process to participants. RESULTS: 101 events were used to create an initial error
      classification. This contained six categories: prescriptions, communication,
      appointments, equipment, clinical care, and "other" errors. Subsequently, 940
      errors were recorded in a single 2 week period from 10 practices, providing
      additional information. 42% (397/940) were related to prescriptions, although
      only 6% (22/397) of these were medication errors. Communication errors accounted
      for 30% (282/940) of errors and clinical errors 3% (24/940). The overall error
      rate was 75.6/1000 appointments (95% CI 71 to 80). The method of error reporting
      was found to be acceptable by 68% (36/53) of respondents with only 8% (4/53)
      finding the process threatening. CONCLUSION: We have developed a classification
      of errors and described a practical and acceptable method for reporting them that
      can be used as part of the process of risk management. Errors are common and,
      although all have the potential to lead to an adverse event, most are
      administrative.

PMID- 14645761
TI  - Improvement, trust, and the healthcare workforce.
AB  - Although major defects in the performance of healthcare systems are well
      documented, progress toward remedy remains slow. Accelerating improvement will
      require large shifts in attitudes toward and strategies for developing the
      healthcare workforce. At present, prevailing strategies rely largely on outmoded
      theories of control and standardisation of work. More modern, and much more
      effective, theories of production seek to harness the imagination and
      participation of the workforce in reinventing the system. This requires a
      workforce capable of setting bold aims, measuring progress, finding alternative
      designs for the work itself, and testing changes rapidly and informatively. It
      also requires a high degree of trust in many forms, a bias toward teamwork, and a
      predilection toward shouldering the burden of improvement, rather than blaming
      external factors. A new healthcare workforce strategy, founded on these
      principles, will yield much faster improvement than at present.

PMID- 14645762
TI  - Psychological contribution to the understanding of adverse events in health care.
AB  - In the past it has sometimes been assumed in health care that all adverse events
      involve individual incompetence and therefore blameworthiness, an assumption that
      is likely to hinder the development of comprehensive and honest incident
      reporting systems. At the same time, a full understanding of adverse events in
      healthcare systems requires that distinctions are drawn between a variety of
      error types, each of which has different origins and demands different strategies
      for remediation. In this paper a range of cognitive biases identified by
      psychologists is described. Examples are given of these biases, which are
      naturally employed in trying to understand our own behaviour and that of others,
      and therefore affect our understanding of adverse events. It is suggested that
      awareness of these biases, which form part of our normal thinking, should help to
      avoid a narrow focus on individual culpability and facilitate a more
      sophisticated approach to the investigation of adverse events.

PMID- 14645763
TI  - Statistical process control as a tool for research and healthcare improvement.
AB  - Improvement of health care requires making changes in processes of care and
      service delivery. Although process performance is measured to determine if these
      changes are having the desired beneficial effects, this analysis is complicated
      by the existence of natural variation-that is, repeated measurements naturally
      yield different values and, even if nothing was done, a subsequent measurement
      might seem to indicate a better or worse performance. Traditional statistical
      analysis methods account for natural variation but require aggregation of
      measurements over time, which can delay decision making. Statistical process
      control (SPC) is a branch of statistics that combines rigorous time series
      analysis methods with graphical presentation of data, often yielding insights
      into the data more quickly and in a way more understandable to lay decision
      makers. SPC and its primary tool-the control chart-provide researchers and
      practitioners with a method of better understanding and communicating data from
      healthcare improvement efforts. This paper provides an overview of SPC and
      several practical examples of the healthcare applications of control charts.

PMID- 14645764
TI  - Learning from samples of one or fewer. 1991.
AB  - Organizations learn from experience. Sometimes, however, history is not generous
      with experience. We explore how organizations convert infrequent events into
      interpretations of history, and how they balance the need to achieve agreement on
      interpretations with the need to interpret history correctly. We ask what methods
      are used, what problems are involved, and what improvements might be made.
      Although the methods we observe are not guaranteed to lead to consistent
      agreement on interpretations, valid knowledge, improved organizational
      performance, or organizational survival, they provide possible insights into the
      possibilities for and problems of learning from fragments of history.

PMID- 14645767
TI  - Healthcare leaders test a proven business strategy.

PMID- 14645768
TI  - Realizing Engel's vision: psychosomatic medicine and the education of physician
      healers.
AB  - Many of the exciting conceptual and scientific advances in the field of
      psychosomatic medicine are not taught in United States medical schools. This
      article, based on the Presidential Address given at the Annual Meeting of the
      American Psychosomatic Society in Phoenix, Arizona in March 2003, reviews the
      rationale for integrating psychosomatic medicine into medical curricula,
      identifies educational needs, proposes a core curriculum, and suggests how
      American Psychosomatic Society members can be instrumental in curriculum
      development and implementation.

PMID- 14645769
TI  - Disease management for depression and at-risk drinking via telephone in an older
      population of veterans.
AB  - OBJECTIVES: The purpose of this study was to explore the efficacy in a primary
      care setting of a telephone-based disease management program for the acute
      management of depression and/or at-risk drinking. MATERIALS AND METHODS: Veterans
      (N= 97) with depression and/or at-risk drinking were identified by systematic
      screening and assessment. Eligible subjects received either telephone disease
      management (TDM) program or usual care based on random assignment of their
      clinician. The TDM program consisted of regular contacts with each subject by a
      behavioral health specialist (BHS) to assist in assessment, education, support,
      and treatment planning. Symptomatic outcomes were assessed at 4 months. RESULTS:
      Overall response rates favored those assigned to TDM compared with those assigned
      to usual care (39.1% responded vs. 17.6%, p= 0.022). Response rates within the
      separate diagnostic groups also favored TDM, but this was only significant for
      depressive disorders. CONCLUSIONS: Although the sample size was modest and the
      sample was limited to veterans, findings strongly suggest that a telephone-based
      disease management program can improve outcomes for patients with a behavioral
      health problem. Findings also suggest that a health specialist can focus and
      manage patients with different diagnoses, thus expanding the role beyond just
      depression care. TDM may be a viable, low-cost, model for primary care clinicians
      to deliver manual guideline-adherent behavioral health care, especially in a VA
      clinical setting.

PMID- 14645770
TI  - Effect on disability outcomes of a depression relapse prevention program.
AB  - OBJECTIVE: This report evaluates the effects of a depression relapse prevention
      program on disability outcomes among patients treated for depression at high risk
      for relapse. MATERIALS AND METHODS: Primary care patients initiating
      antidepressant treatment for depression were assessed 6 to 8 weeks after the
      initial prescription. Patients responding to initial treatment but at high risk
      for relapse were randomized to usual care or a relapse prevention intervention
      (N= 386). The 12-month relapse prevention program included systematic patient
      education, two psycho-educational visits with a depression prevention specialist,
      shared decision-making regarding maintenance pharmacotherapy, and ongoing
      monitoring of medication adherence and depressive symptoms via telephone and
      mail. Disability outcomes were assessed via blinded telephone assessments at 3,
      6, 9, and 12 months using SF-36 and Sheehan Disability scales. RESULTS: Usual
      care patients and relapse prevention program patients had high rates of use of
      maintenance pharmacotherapy. Both relapse prevention and usual care patients
      showed improved functioning over the 12-month follow-up period. One of the three
      disability measures (the SF-36 Social Function scale) showed a significant
      intervention effect because of continuing improvement at 9 and 12 month follow
      up, whereas the Sheehan Disability Scale showed a nonsignificant trend toward
      greater improvements in disability among relapse prevention patients than among
      usual care controls. CONCLUSIONS: Moderate effects of a relapse prevention
      intervention on depressive symptoms were associated with modest and variable
      effects on disability outcomes. Inconsistent effects of the intervention for
      disability outcomes may be because of the high rates of maintenance
      pharmacotherapy among usual care patients, relatively mild levels of depressive
      symptoms among both intervention and control patients at baseline, the absence of
      a specific relapse prevention effect of the intervention, and the resultant
      modest differences in depressive symptoms between intervention and control
      patients in this trial.

PMID- 14645771
TI  - Female gender is associated with impaired quality of life 1 year after coronary
      artery bypass surgery.
AB  - OBJECTIVE: To evaluate gender-related differences in quality of life (QOL) and
      cognitive function 1 year after coronary artery bypass surgery (CABG) after
      adjusting for known baseline differences. MATERIALS AND METHODS: Two hundred
      eighty patients (96 women and 184 men) underwent neurocognitive and QOL
      evaluation at baseline (preoperatively) and at 1 year after CABG. Multivariable
      linear regression was used to assess the relationship of gender to follow-up QOL
      and cognitive function. Measures used to evaluate QOL were IADL, DASI, work
      activities (SF-36), social activities, social support, general health perception
      (SF-36), CESD, STAI, and symptom limitations. Cognitive function was measured
      with a battery of performance-based neuropsychological tests, reduced to a four
      cognitive domain scores with factor analysis, and a self-report measure of
      cognitive difficulties. Covariates in multiple regression models included age,
      years of education, marital status, Charlson Comorbidity Index, hypertension,
      diabetes, race, and baseline QOL/cognitive status. RESULTS: Female patients
      showed significantly worse outcome than male patients at 1 year follow-up in
      several key areas of QOL. After adjusting for baseline differences, women are at
      greater risk for increased cognitive difficulties (p= 0.04) and anxiety (p=
      0.03), as well as impaired DASI (p= 0.02), IADL (p= 0.03), and work activities
      (p= 0.02). Cognitive sequelae attributable to bypass surgery were similar between
      men and women. CONCLUSIONS: Even after adjusting for known risk factors for
      compromised QOL and cognitive functioning, women do not show the same long-term
      quality benefits of CABG surgery that men do.

PMID- 14645773
TI  - Anxiety and chronic obstructive pulmonary disease: prevalence, impact, and
      treatment.
AB  - OBJECTIVE: This article reviews the prevalence of anxiety disorders in patients
      with chronic obstructive pulmonary disease (COPD) as well as the impact of
      comorbid anxiety on quality of life in patients with COPD. Published studies on
      three types of treatments for anxiety are then reviewed: psychopharmacology,
      psychotherapy, and pulmonary rehabilitation programs. MATERIALS AND METHODS: A
      PubMed search was conducted of the literature from 1966 through 2002 using the
      keywords anxiety, chronic obstructive pulmonary disease, respiratory diseases,
      obstructive lung diseases, and pulmonary rehabilitation. Any articles that
      discussed the prevalence of anxiety symptoms or anxiety disorders among patients
      with COPD, the impact of anxiety on patients with COPD, or the treatment of
      anxiety in COPD patients were included in this review. RESULTS: Anxiety
      disorders, especially generalized anxiety disorder (GAD) and panic disorder,
      occur at a higher rate in patients with COPD compared with the general
      population. Not surprisingly, anxiety has a significant and negative impact on
      quality of life of COPD patients. Nonetheless, few studies have examined
      pharmacological, psychotherapeutic, or pulmonary rehabilitation treatments for
      anxiety disorders in the context of COPD. Trials of nortriptyline, buspirone, and
      sertraline have been found to reduce symptoms of anxiety. Similarly, cognitive
      behavioral programs that focus on relaxation and changes in thinking also
      produced declines in anxious symptoms. Finally, multicomponent pulmonary
      rehabilitation programs can also result in reductions in anxious symptoms.
      CONCLUSIONS: Studies examining the treatment of anxiety disorders in patients
      with COPD are promising, yet their efficacy needs to be established. The long
      term effects of treatment of anxiety disorders on quality of life of COPD
      patients have yet to be explored.

PMID- 14645772
TI  - Marital status, marital quality, and atherosclerotic burden in postmenopausal
      women.
AB  - Marriage confers health benefits for men, but the evidence for women is less
      consistent. Inconsistent findings may be attributed, in part, to the confounding
      of marital status and marital quality. OBJECTIVES: The authors examined whether
      women in satisfying marriages evidence lesser atherosclerosis relative to women
      in low-satisfying marriages and relative to unmarried women. MATERIALS AND
      METHODS: Three hundred ninety-three women from the Healthy Women Study
      participated in this study. Marital status and quality were assessed at baseline
      when women were premenopausal. Cardiovascular risk factors were also assessed at
      baseline to determine potential mediators. Markers of atherosclerotic burden--B
      Mode ultrasound measures of intima-media thickness and plaque in the carotid
      arteries and electron beam computed tomography assessments of calcification in
      the aorta and coronary arteries--were performed, on average, 11 years and 14
      years later, respectively. A subset of women underwent a second ultrasound scan
      approximately 3 years after their first scan. RESULTS: Women in satisfying
      marriages had the least atherosclerosis in the carotid arteries and aorta,
      especially relative to those in low-satisfying marriages. Women in satisfying
      marriages also tended to show less rapid progression of carotid atherosclerosis
      relative to women in low-satisfying marriages. Women who did not have a partner
      had intermediate levels of atherosclerosis. Risk factors measured at baseline
      contributed to the differences between the satisfied and low-satisfied groups,
      but not those between the satisfied and unmarried groups. CONCLUSIONS: High
      quality marriages may protect against cardiovascular disease for women. Studies
      concerning marriage and cardiovascular health in women should, therefore,
      concurrently examine marital quality and marital status.

PMID- 14645774
TI  - Relationship between behavior and asthma in children with atopic dermatitis.
AB  - OBJECTIVE: The significance of psychological factors in asthma is a subject of
      considerable dispute. This study addressed the little investigated question of
      the potential role of psychological factors in the initial onset of asthma.
      MATERIALS AND METHODS: Data on the validated, standardized Behavior Screening
      Questionnaire were obtained prospectively from 35 to 53 months for 150 atopic
      children who had asthma by age 53 months and for 115 who did not. RESULTS: At
      each age, the children who had asthma by 53 months had more behavior problems.
      There was no evidence that the subsequent behavior of those children who had
      asthma became more problematic. However, for those children without asthma by 35
      months, an elevated behavior problem score at that age was related to the
      subsequent onset of asthma by age 53 months. The behavior problem score added
      significantly to the prediction of asthma onset (OR adjusted: 1.15; 95% CI: 1.02
      1.29) when known risk factors of asthma and IgE levels for grass pollen and house
      dust mite at age 17 months were taken into account. CONCLUSIONS: Behavior
      problems may precede asthma onset in young atopic children. In this age group,
      behavior problems are not secondary psychological reactions to asthma onset. They
      may act as a marker for stress in the child's life. The presence of behavior
      problems should alert clinicians that the child may be at increased risk for
      transition from atopic dermatitis to asthma.

PMID- 14645775
TI  - Resting end-tidal CO2 and negative affectivity.
AB  - OBJECTIVE: Dhokalia, Parsons, and Anderson (Psychosom Med 1998;60:33-37) found a
      positive correlation between a trait measure of negative affectivity (NA;
      neuroticism) and resting end-tidal fractional concentration of CO2 (FetCO2)
      (fractional-concentration of end-tidal carbon dioxide) in a nonclinical sample.
      This contrasts sharply with studies reporting a negative association of FetCO2
      with state measures of NA and with studies reporting no or a negative
      relationship between FetCO2 and trait NA. In two studies we aimed to clarify this
      paradox. MATERIALS AND METHODS: In the first study, 110 participants (83 women)
      completed the PANAS and a Checklist for Psychosomatic Symptoms in daily life.
      FetCO2 was measured noninvasively during 5 minutes via a nose cannula connected
      to a capnograph. In the second study, FetCO2 of high (N= 20, 10 men) and low (N=
      20, 10 men) NA participants was sampled once with a nasal cannula and once while
      breathing through a mouthpiece for 6 minutes each during rest, completion of the
      NEO-PI-R questionnaire, and completion of a verbal knowledge test. RESULTS: The
      first study found no association between trait NA and resting FetCO2 after
      partialling out the effects of gender, menstrual phase, and use of oral
      contraceptives. The second study showed that FetCO2 increased significantly in
      the high NA group only when the particpants filled out the questionnaires,
      regardless of its type. CONCLUSIONS: Overall, no association between
      dispositional NA and cross-situational FetCO2 was observed. Apparently
      inconsistent findings may be caused by lack of control for hormonal status and
      mental load during testing.

PMID- 14645776
TI  - Socioeconomic status, stress, and immune markers in adolescents with asthma.
AB  - OBJECTIVE: Previous research has demonstrated links between low socioeconomic
      status (SES) and clinical asthma outcomes, as well as links between stress and
      asthma. The objective of this study was to test whether adolescents with asthma
      from different SES backgrounds differed in biological profiles relevant to
      asthma, including immune and cortisol measures. The second objective was to test
      whether psychological stress and control beliefs could explain these differences.
      MATERIALS AND METHODS: Adolescents with persistent asthma from either low (N= 18)
      or high (N= 12) SES neighborhoods were interviewed about their stress experiences
      (chronic stress, acute life events, interpretations of ambiguous life events) and
      control beliefs. Blood was drawn to assess immune (cytokines, eosinophils, IgE)
      and neuroendocrine (cortisol) markers associated with asthma. RESULTS:
      Adolescents in the low SES group had significantly higher levels of a stimulated
      cytokine associated with a Th-2 immune response (IL-5), higher levels of a
      stimulated cytokine associated with a Th-1 immune response (IFN-gamma), and
      marginally lower morning cortisol values compared with the high SES group. Low
      SES adolescents also had greater stress experiences and lower beliefs about
      control over their health. Statistical mediational analyses revealed that stress
      and control beliefs partially explained the relationship between SES and IL-5/IFN
      gamma. CONCLUSION: Our finding that low SES was associated with elevations in
      certain immune responses (IL-5/IFN-gamma) in adolescents with asthma suggests the
      importance of further exploration into relationships between SES and Th-2/Th-1
      responses in asthma. Our findings also suggest that psychological stress and
      control beliefs may provide one explanation for links between SES and immune
      responses in childhood asthma.

PMID- 14645777
TI  - Relationship of self-reported asthma severity and urgent health care utilization
      to psychological sequelae of the September 11, 2001 terrorist attacks on the
      World Trade Center among New York City area residents.
AB  - OBJECTIVE: Posttraumatic psychological stress may be associated with increases in
      somatic illness, including asthma, but the impact of the psychological sequelae
      of the September 11, 2001 terrorist attacks on physical illness has not been well
      documented. The authors assessed the relationship between the psychological
      sequelae of the attacks and asthma symptom severity and the utilization of urgent
      health care services for asthma since September 11. MATERIALS AND METHODS: The
      authors performed a random digit dial telephone survey of adults in the New York
      City (NYC) metropolitan area 6 to 9 months after September 11, 2001. Two thousand
      seven hundred fifty-five demographically representative adults including 364
      asthmatics were recruited. The authors assessed self-reported asthma symptom
      severity, emergency room (ER) visits, and unscheduled physician office visits for
      asthma since September 11. RESULTS: After adjustment for asthma measures before
      September 11, demographics, and event exposure in multivariate models
      posttraumatic stress disorder (PTSD) were a significant predictor of self
      reported moderate-to-severe asthma symptoms (OR = 3.4; CI = 1.2-9.4), seeking
      care for asthma at an ER since September 11 (OR = 6.6; CI = 1.6-28.0), and
      unscheduled physician visits for asthma since September 11 (OR = 3.6; CI = 1.1
      11.5). The number of PTSD symptoms was also significantly related to moderate-to
      severe asthma symptoms and unscheduled physician visits since September 11.
      Neither a panic attack on September 11 nor depression since September 11 was an
      independent predictor of asthma severity or utilization in multivariate models
      after September 11. CONCLUSIONS: PTSD related to the September 11 terrorist
      attacks contributed to symptom severity and the utilization of urgent health care
      services among asthmatics in the NYC metropolitan area.

PMID- 14645778
TI  - Implementing psychiatric interventions on a medical ward: effects on patients'
      quality of life and length of hospital stay.
AB  - OBJECTIVE: The authors investigated the effects of implementing psychiatric
      interventions on a general medical ward by means of a stepped detection and
      treatment strategy conducted by a consultation-liaison (CL) nurse in terms of
      reducing length of hospital stay (LOS) and improving quality of life (QOL) at
      discharge. MATERIALS AND METHODS: One hundred ninety-three patients participated
      in a controlled trial, in which patients were screened with COMPRI and INTERMED.
      A nurse under supervision of a CL psychiatrist conducted interventions,
      consisting of simple psychiatric interventions by herself, referral to auxiliary
      services, or initiation of postdischarge care. Intervention patients were
      compared with historic controls on LOS and QOL (SF36) at discharge. RESULTS: In
      multivariate analysis of variance, a significant effect of the intervention on
      QOL (p = 0.037) was found, which diminished after controlling for confounders (p
      = 0.28). No significant effect on LOS was found for the whole sample (p = 0.72),
      but in patients age 65 years or older, a reduction in LOS (p = 0.05) was found.
      This effect remained after controlling for confounders (p = 0.06). CONCLUSIONS:
      These data suggest that screening for risk of increased health care might improve
      outcomes in general medical inpatients. Because of the design of the study,
      however, these findings should be considered preliminary and confirmed in a
      larger, multicenter, randomized controlled trial.

PMID- 14645779
TI  - Hostility, interpersonal interactions, and ambulatory blood pressure.
AB  - OBJECTIVE: This study examined aspects of the transactional model of hostility
      and health by investigating relationships among hostility, interpersonal
      interactions, and ambulatory blood pressure in a healthy community sample.
      MATERIALS AND METHODS: Participants included 65 female and 39 male healthy adults
      between the ages of 18 and 46 years. Ambulatory blood pressure (ABP) and diary
      data on mood and social interactions were obtained every 20 minutes for 1 day.
      Mixed models regression analyses were used to evaluate the relationships among
      hostility, interpersonal interactions, and ABP. RESULTS: Trait hostility was
      positively associated with the frequency and intensity of negative interactions
      and was negatively associated with the frequency and intensity of positive
      interactions. Interacting with others was associated with increases in systolic
      blood pressure (SBP) and diastolic blood pressure (DBP). The magnitude of the
      increase in blood pressure was positively associated with the degree to which the
      interaction was perceived as negative. Hostility was not directly associated with
      ABP/heart rate (HR) or ABP/HR responses during any interactions or negative
      interactions. However, there was an interaction between hostility and negative
      interaction intensity for DBP, suggesting that hostility moderates the effects of
      negative interactions on DBP. Specifically, increases in the intensity of
      negative interactions were associated with increases in DBP for participants with
      high, but not low, hostility. CONCLUSIONS: The results provide partial support
      for the notion that hostility may be associated with risk for cardiovascular
      disease through its effects on interpersonal interactions and their
      cardiovascular correlates.

PMID- 14645780
TI  - Parental history of hypertension and coping responses predict blood pressure
      changes in black college volunteers undergoing a speaking task about perceptions
      of racism.
AB  - OBJECTIVE: This investigation explored the relationship of coping responses and
      parental history of hypertension to task-induced blood pressure changes.
      MATERIALS AND METHODS: The sample consisted of 215 black college student
      volunteers (median age = 25.95 y). During the speaking task, participants
      responded to standardized questions about perceptions of intra-ethnic and inter
      ethnic group racism. Systolic blood pressure and diastolic blood pressure were
      measured via an automated blood pressure monitor. Usual ways of coping with intra
      ethnic group racism were assessed with the COPE Scale, and parental history of
      hypertension (PHH) was self-reported by participants. RESULTS: Findings from the
      final step of hierarchical general linear models indicated that the main effect
      of emotion-focused coping was negatively associated with diastolic blood pressure
      (p = 0.02) and systolic blood pressure (p = 0.002) changes. Further, these
      analyses revealed that PHH interacted: (1) with the coping responses of planning
      (p = 0.007) and denial (p = 0.002) to predict changes in systolic blood pressure
      and (2) with the planning coping response to predict diastolic blood pressure
      changes (p = 0.02). The direction of these effects indicated that among
      participants who were high in these coping responses, participants who also had a
      positive PHH had larger blood pressure changes. Regression analyses also revealed
      that PHH interacted with the cognitive coping response (p = 0.01) to predict
      changes in systolic blood pressure. The direction of this effect indicated that
      among participants who were low in this coping response, participants who also
      had a positive PHH had larger systolic blood pressure changes. CONCLUSION: This
      study highlights the importance of examining the joint contribution of biological
      and psychosocial parameters to blood pressure reactivity in blacks.

PMID- 14645781
TI  - Do childhood adversity and recent social stress predict health care use in
      patients presenting with upper abdominal or chest pain?
AB  - OBJECTIVE: A comprehensive model of health care use by patients with functional
      gastrointestinal disorders has not been fully tested. This study aimed to
      establish whether reported childhood and/or recent adversity are independent
      predictors of health care use when all other relevant factors are also included
      in the model. MATERIALS AND METHODS: Consecutive new patients with upper
      abdominal or chest pain presenting to a secondary/tertiary clinic were assessed
      using the Childhood Experience of Care and Abuse and Life Events and Difficulties
      Schedules. They completed the Hospital Anxiety and Depression and Health Anxiety
      Questionnaires. Outcome was total number of health care visits recorded in
      hospital and general practice (GP) records over 18 months. RESULTS: One hundred
      fifty-one patients were included (65% response rate). Health care visits were
      most frequent in unmarried (p < 0.0005), females (p < 0.0005), and those lacking
      social support (p = 0.012). In multiple regression analysis to predict number of
      health care visits, reported sexual abuse (p = 0.042) and death of a sibling
      during childhood (p = 0.026) were also independent predictors, together with SF36
      subscale scores for physical function, health perception, and mental health (35%
      of variance explained). Childhood adversity predicted health care use in patients
      with functional gastrointestinal disorders and recent social stress did so in
      patients with demonstrated pathological findings. CONCLUSION: After adjustment
      for demographic, physical, and psychological factors, childhood adversity,
      especially in severe form, is an independent predictor of health care use in
      patients with upper functional gastrointestinal disorders. The same was not true
      for patients consulting for demonstrable pathological abnormalities, for whom
      ongoing social stress was an independent predictor.

PMID- 14645782
TI  - Burden of psychosocial adversity and vulnerability in middle age: associations
      with biobehavioral risk factors and quality of life.
AB  - OBJECTIVES: Numerous psychosocial factors are associated with disease risk. This
      study investigated the possibility that a combination of chronic stress from
      exposure to multiple sources and absence of protective psychosocial resources
      would be related to heightened emotional distress, health risk behavior,
      biological risk factors, and impaired quality of life, independently of
      socioeconomic position (SEP). MATERIALS AND METHODS: Data were analyzed from 227
      men and women aged 47 to 59 years from the Whitehall II epidemiological cohort. A
      psychosocial adversity and vulnerability index (PAVIX) was constructed from high
      scores on measures of job demands, neighborhood stress, and financial strain, low
      emotional support, limited social networks, low active coping, and low sense of
      control. RESULTS: The measures making up the PAVIX were relatively independent of
      one another. Scores on the PAVIX were greater in lower SEP participants, and in
      single, separated, or divorced than married participants. The PAVIX was
      positively associated with psychological distress, depression, hopelessness,
      sleep problems, hostility, low self-esteem and loneliness, independently of age,
      sex, SEP, and marital status. There were no associations with health behaviors,
      but relationships were observed with glycohemoglobin, plasma fibrinogen, plasma
      viscosity, and body mass (women), that were again independent of covariates.
      Individuals with high PAVIX scores also reported impaired health-related quality
      of life. DISCUSSION: The accumulated burden of life stress coupled with limited
      protective psychosocial resources is associated with adverse psychological,
      biological, and quality of life outcomes. This integrated approach to the
      investigation of psychosocial factors may prove valuable in understanding
      etiological processes.

PMID- 14645783
TI  - Coping effectiveness training for men living with HIV: results from a randomized
      clinical trial testing a group-based intervention.
AB  - OBJECTIVE: This randomized clinical trial was designed to compare the effects of
      a theory-based coping effectiveness training (CET) intervention with an active
      informational control (HIV-Info) condition and a waiting-list control (WLC)
      condition on psychological distress and positive mood in HIV-seropositive gay
      men. MATERIALS AND METHODS: The authors recruited 149 self-identified gay or
      bisexual men who were 21 to 60 years of age, reported depressed mood, and had CD4
      levels of 200 to 700 cells/mm(3). CET and HIV-Info participants attended 10 90
      minute group sessions during the 3-month intervention phase and six maintenance
      sessions over the remainder of the year. Participants were assessed at baseline
      and at 3, 6, and 12 months. Data were collected 1992 to 1994, before the
      introduction of HAART. Analyses were based on the 128 participants who completed
      the 3-month assessment. RESULTS: After the 3-month intervention phase, when
      compared with HIV-Info, CET participants showed significantly greater decreases
      in perceived stress and burnout, and regression analyses indicated that
      significant increases in coping self-efficacy mediated the improvements in
      perceived stress and burnout. Compared with WLC, CET participants also showed
      significantly greater decreases in anxiety, and regression analyses indicated
      that significant increases in positive states of mind mediated the improvements
      in anxiety. Significant treatment group differences for positive morale were
      maintained at 6 and 12 months. In addition, optimism continued to increase in the
      CET and HIV-Info treatment groups during the maintenance phase. CONCLUSIONS: CET
      can be an effective strategy for managing psychological distress and improving
      positive psychological states in patients confronting chronic illness.

PMID- 14645784
TI  - Prospective study of the prognosis of unexplained chronic fatigue in a clinic
      based cohort.
AB  - OBJECTIVES: To determine prospective changes in clinical status related to
      chronic fatigue over an 18-month period, and to test demographic and clinical
      predictors of outcome. METHODS: A cohort of 100 patients with unexplained chronic
      fatigue (UCF), which encompasses both chronic fatigue syndrome (CFS) and
      idiopathic chronic fatigue (ICF), completed questionnaire measures and medical
      and psychiatric evaluations on four occasions, each six months apart. RESULTS:
      Approximately 21% of the sample did not meet criteria for either CFS or ICF at
      their last research appointment 1.5 years after their index visit. Vitality
      increased over time, and physical functioning tended to improve, but UCF symptoms
      did not decrease significantly. Less education, being unemployed, worse mental
      health, more use of sedating and antidepressant medications, and more somatic
      attributions for their symptoms were associated with worsening symptom severity
      over time. Older age, current depression, and more somatic attributions predicted
      worsening physical functioning. Better mental health, less use of sedating
      medications, and fewer somatic attributions for illness were significant
      predictors of increases in vitality. CONCLUSIONS: Demographic and clinical
      variables predict outcomes over time among a cohort of patients with unexplained
      chronic fatigue.

PMID- 14645785
TI  - Use and abuse of academic examinations in stress research.
AB  - Previous research suggests that certain types of academic examinations can have a
      significant impact on psychological and physical health. However, there has not
      been adequate discussion about the methodological and statistical issues
      associated with using academic examinations as a model for short-term stress in
      the context of psychoneuroimmunology research. Limitations of the model are
      presented with recommendations for appropriate use. Specific suggestions include
      use of subjective and objective measures of test difficulty, within-subjects
      designs including measurements during the examination itself, statistical models
      for testing interactions of continuous variables, and participants with clinical
      conditions.

PMID- 14645786
TI  - Blood pressure reactions to stress and the prediction of future blood pressure:
      effects of sex, age, and socioeconomic position.
AB  - OBJECTIVE: This epidemiological study examined whether the magnitude of blood
      pressure reactions to mental stress was associated with future blood pressure and
      whether the strength of association was affected by sex, age, and socioeconomic
      position. MATERIALS AND METHODS: Resting blood pressure was recorded at initial
      baseline and in response to mental stress. Five-year follow-up resting blood
      pressure data were available for 990 (68%) of the participants; 333 were 23 years
      old at the time of stress testing, 427 were 43, and 230 were 63. There were 541
      women and 449 men; 440 came from manual and 550 from nonmanual occupation
      households. RESULTS: Systolic blood pressure reactions to stress correlated
      positively with follow-up systolic blood pressure; no association was found for
      diastolic blood pressure reactions and follow-up diastolic blood pressure. In
      multivariate tests, systolic reactivity remained predictive of follow-up systolic
      blood pressure and accounted for 2.3% of the variance not explained by age, body
      mass index, and initial baseline systolic blood pressure. Systolic and diastolic
      reactivity predicted 5-year upward drift in systolic and diastolic blood pressure
      respectively, accounting for an additional 3.6% and 2.9% of variance,
      respectively, in multivariate models. The predictive value of reactivity was
      greater for participants from manual occupation households and tended to be
      greater for men. CONCLUSIONS: The results of this study indicate that blood
      reactions to mental stress predict future blood pressure status and the increase
      in resting blood pressure over time. The magnitude of the prediction appears to
      vary with socioeconomic position and sex.

PMID- 14645787
TI  - Socioemotional correlates of self-reported menstrual cycle irregularity in
      premenopausal women.
AB  - OBJECTIVE: Characteristics of menstrual functioning are associated with social
      rank and corresponding behavioral expression of dominance and subordination in
      female cynomolgus macaques. Extrapolating from this research, the present study
      examined socioemotional correlates of menstrual cycle irregularity in
      premenopausal women by focusing on the dimensions of dominance/submission and
      hostility/warmth. MATERIALS AND METHODS: Participants were 153 premenopausal
      women (70 African-Americans, 83 European-Americans) who reported no current use
      of hormonal contraceptives. All women completed measures of socioemotional traits
      and reported whether the onset of their menstrual cycles was generally
      predictable within 4 days over the course of the past year. RESULTS: Menstrual
      cycle irregularity was significantly and positively associated with the
      socioemotional trait of submission. This association held after adjusting for age
      and a number of potentially confounding health behaviors. CONCLUSIONS: Results
      are consistent with the notion that menstrual functioning is sensitive to
      socioemotional processes, particularly those pertaining to social hierarchies.
      Given recent findings linking menstrual cycle irregularity to cardiovascular
      disease, the results of the present study highlight new biobehavioral pathways to
      be explored with regard to women's cardiovascular disease risk.

PMID- 14645788
TI  - The mental health crisis that wasn't.

PMID- 14645790
TI  - Datapoints: do participants in alcoholism treatment outcome studies resemble
      patients seen in everyday practice?

PMID- 14645792
TI  - Economic grand rounds: financial disincentives for the provision of
      psychotherapy.

PMID- 14645793
TI  - Multimedia reviews: multimedia convergence for clinicians.
AB  - Introduction by the column editor: In this final column of the year, Dr. Taintor
      provides an overview of exciting technological developments via his report on the
      2003 annual meeting of the American Association for Technology in Psychiatry
      (AATP). Advances-and convergences-in technology are providing clinicians with
      increasingly useful tools to enhance the effectiveness of their treatments,
      increase access to care, reduce errors, and save time. As Dr. Taintor notes,
      AATP's meeting is traditionally held in conjunction with the annual meeting of
      the American Psychiatric Association (APA). I hope that his report will encourage
      APA's members to attend some of next year's informative sessions.

PMID- 14645794
TI  - Clinical computing: monitoring patients with eating disorders by using e-mail as
      an adjunct to clinical activities.

PMID- 14645795
TI  - Emergency psychiatry: an emergency treatment hub-and-spoke model for psychiatric
      emergency services.

PMID- 14645796
TI  - Practical geriatrics: psychodynamic psychotherapy with older adults.

PMID- 14645797
TI  - Personal accounts: surviving suicide: the ones left behind.

PMID- 14645798
TI  - Patient safety forum: examining the evidence: do we know if psychiatric
      inpatients are being harmed by errors? What level of confidence should we have in
      data on the absence or presence of unintended harm?

PMID- 14645799
TI  - Recent advances in telepsychiatry: an updated review.
AB  - OBJECTIVE: In response to new developments and interest in the area of
      telepsychiatry, literature on this topic has greatly increased over the past
      three years. Because of this increase, the authors conducted a literature review
      of telepsychiatry to update a previously published review that covered the years
      1970 to 2000. METHODS: A search was conducted on the MEDLINE, PsycINFO, and
      Telemedicine Information Exchange (TIE) databases for literature published from
      March 2000 to March 2003 on telepsychiatry applications, using the following
      terms: telepsychiatry, telepsychology, telemental health, videoconferencing, and
      video conferencing. RESULTS: Sixty-eight publications were identified over this
      three-year period, exceeding the 63 publications identified in the previous
      literature review. The authors summarize the results of findings in six areas:
      novel clinical demonstrations and current program descriptions; the reliability
      of clinical assessments; clinical outcomes; satisfaction of patients and
      clinicians; cost and cost-effectiveness; and legal, regulatory, and ethical
      issues. Studies describing existing programs and novel clinical applications
      support the belief that the use of telepsychiatry is expanding. Overall, studies
      continued to support the notion that telepsychiatry assessments can produce
      reliable results, telepsychiatric services can lead to improved clinical status,
      and patients and clinicians are satisfied with treatment delivered via
      telepsychiatry. Evidence supported the notion that telepsychiatry is a cost
      effective means of delivering mental health services; however, this conclusion
      was based on limited studies of economic models of telepsychiatry programs. Also
      limited were papers on the topics of legal, regulatory, and ethical issues.
      CONCLUSIONS: Despite the rapid increase in information on telepsychiatry,
      methodologically sound studies in the area of telepsychiatry are still
      infrequent.

PMID- 14645800
TI  - Post-september 11 admission symptoms and treatment response among veterans with
      posttraumatic stress disorder.
AB  - OBJECTIVE: Evidence has been found of significant psychological distress after
      the terrorist attacks of September 11, 2001, even in communities that were not
      directly affected. Persons with preexisting posttraumatic stress disorder (PTSD)
      may be especially vulnerable to such distress. The authors examined clinical data
      on veterans who had a diagnosis of PTSD to determine whether the attacks
      exacerbated their symptoms. METHOD: S: Outcome-monitoring data were analyzed from
      a national sample of more than 9,000 veterans who were treated in specialized
      intensive PTSD programs of the Department of Veterans Affairs (VA) from March 11,
      1999, to March 11, 2002. Analysis of variance was used to compare symptom levels
      at admission and clinical improvement during the six months before and six months
      after September 11 and in comparison with the same periods in 1999 and 2000.
      RESULTS: Veterans who were admitted after September 11, 2001, had less severe
      symptoms than those admitted before September 11, a pattern that was
      significantly different from previous years. Veterans who were followed up after
      September 11 showed significantly more improvement in PTSD symptoms than those
      who were followed up before then, which also represented a significant difference
      from previous years. CONCLUSION: S: VA patients with preexisting PTSD were,
      unexpectedly, less symptomatic at admission after September 11 than veterans
      admitted before September 11, and patients who had follow-up assessments after
      September 11 showed more improvement. It is possible that these veterans
      benefited from the shared feelings of national unity, pride, and patriotism in
      the months after September 11 as well as from the normalization of PTSD-like
      reactions by the news media and a sense of mastery at having past experience in
      coping with trauma.

PMID- 14645801
TI  - Prescribing patterns for patients with posttraumatic stress disorder.
AB  - OBJECTIVE: The little information available about prescribing patterns for
      persons with posttraumatic stress disorder comes from male combat-veteran
      populations treated through programs of the Department of Veterans Affairs. The
      objective of this study was to comprehensively evaluate prescribing patterns for
      persons with a diagnosis of posttraumatic stress disorder (PTSD) in a community
      based nonveteran sample in which women were well represented. METHODS:
      Prescription claims paid in December 1999 for New Hampshire Medicaid recipients
      with diagnostic codes for PTSD were analyzed. Frequencies of prescriptions for
      categories of medication were compared between patients with PTSD (N=165) and
      patients with major depression alone (N=2,208) and those with major depression co
      occurring with PTSD (N=171). RESULTS: The patients with PTSD were predominantly
      women who were receiving services at community mental health centers. Selective
      serotonin reuptake inhibitors were more frequently prescribed for major
      depression (32 percent of cases) than for PTSD (23 percent). Other novel
      antidepressants were more frequently prescribed for major depression co-occurring
      with PTSD (25 percent of cases) than for major depression alone (18 percent).
      Atypical antipsychotic medications were more frequently prescribed for PTSD (17
      percent of cases) and for major depression co-occurring with PTSD (20 percent)
      than for major depression alone (9 percent). Benzodiazepines and related
      hypnotics, trazodone, and mood stabilizers were more frequently prescribed for
      major depression co-occurring with PTSD than for major depression alone.
      CONCLUSIONS: The findings suggest that many outpatients who have PTSD are treated
      aggressively with medication, particularly when PTSD co-occurs with major
      depression, and that there are discrepancies between actual prescribing patterns
      and prescribing guidelines. These findings overlap trends observed in veteran
      populations.

PMID- 14645802
TI  - Professionals' responsibilities in releasing information to families of adults
      with mental illness.
AB  - OBJECTIVE: Statutes, ethical standards, and local confidentiality guidelines have
      been developed to guide providers' decisions about releasing information from
      mental health records. However, confidentiality policies often do not
      specifically discuss the release of confidential information to the families of
      persons with mental illness. This study examined how providers and family members
      interpret and implement confidentiality policies about the release of information
      to families. METHOD: S: Self-administered surveys were completed by 59 providers
      from outpatient, partial hospitalization, and case management programs in
      Pennsylvania. In-depth interviews were also conducted with a subsample of eight
      providers. In addition, 68 families of persons with mental illness receiving
      services from these providers completed self-administered surveys. RESULTS:
      Ninety-five percent of the providers interpreted confidentiality policies
      conservatively, believing that they could not share confidential information
      without the consent of the client, However, 54 percent were confused about the
      types of information that are confidential. Implementation of confidentiality
      policies varied among the providers. Regression analysis indicated that
      providers' perceptions of confidentiality as a barrier to collaboration were
      significantly associated with their attitudes toward collaboration between the
      providers, consumers, and family members. Few families understood the
      requirements of confidentiality policies or the types of information that are
      confidential. CONCLUSION: S: Confidentiality policies may be posing a barrier to
      collaboration between providers, consumers, and family members, which has been
      recommended by various experts for the treatment of mental illness. Clear
      guidelines for the release of confidential information to families are needed.

PMID- 14645803
TI  - Clinical and forensic outcomes from the Illinois mental health juvenile justice
      initiative.
AB  - OBJECTIVE: To address the mental health needs of youths who are arrested and
      detained in Illinois, an initiative was designed and implemented that identified
      youths with psychotic or affective disorders, linked them to community services,
      and monitored their cases. This study assessed whether such linkage is possible
      and whether it improves clinical and forensic outcomes. METHOD: S: Under the
      initiative, court staff refer youths who may have a mental illness to a clinical
      liaison. If the youth is eligible for the program, the liaison works with the
      family to develop a community-based action plan. For the analysis presented here,
      the Child and Adolescent Needs and Strengths-Mental Health Scale (CANS-MH) and
      the Child and Adolescent Functional Assessment Scale (CAFAS) were used to assess
      outcomes among 314 youths who had completed the program at the time of the study.
      School and forensic outcomes were also monitored. RESULTS: Seventy-five percent
      of the youths were successfully linked to at least one mental health or community
      service. A comparison of average CANS-MH dimension scores at enrollment and
      program completion indicated that youths' emotional problems decreased
      considerably within three months of referral. CAFAS scores six months after
      enrollment improved across nearly all dimensions. Home, community, and school
      functioning were significantly improved from baseline. Only 42 percent of the
      youths were rearrested, compared with a statewide rate of 72 percent of detained
      youths. CONCLUSION: S: By linking youths with significant mental health needs to
      existing community-based services, it appears possible both to ameliorate
      psychopathology and to reduce delinquency.

PMID- 14645804
TI  - Clinical characteristics, cognitive functioning, and criminal histories of
      outpatients with schizophrenia.
AB  - OBJECTIVE: The authors examined the relationships between clinical
      characteristics, cognitive functioning, and history of violent behavior and
      substance use among outpatients with schizophrenia. METHODS: Ninety-six patients
      with a diagnosis of schizophrenia or schizoaffective disorder completed a
      clinical and neuropsychiatric battery that included tests of general
      intelligence, executive and frontal lobe function, visual-motor processing, and
      motor function. Violent behavior was defined on the basis of arrest records. Self
      reported violent behavior and substance use were recorded. The study participants
      were separated into three groups: history of violent arrest (N=34), nonviolent
      arrest (N=23), and no arrest (N=39). The three groups were compared for
      differences in demographic characteristics, clinical symptoms, and scores on
      neuropsychological tests. RESULTS: Fifty-seven (59 percent) of the 96
      participants had a history of arrest. Persons who were arrested for nonviolent
      crimes had a significantly lower mean+/-SD number of arrests (3.39+/-3.7) than
      those arrested for violent crimes (9.24+/-8.9). No significant differences in
      neuropsychological test scores or clinical ratings were found between the three
      groups. The prevalence of substance use disorders was 65 percent, 57 percent, and
      36 percent among patients with a history of violent, nonviolent, and no arrest,
      respectively. Only 47 percent of participants with a criminal history accurately
      reported this history, and 11 percent of participants with a history of drug
      related arrests acknowledged previous substance use. CONCLUSIONS: Performance on
      neuropsychiatric tests does not distinguish stable outpatients with schizophrenia
      who have a history of violent behavior from those who do not have such a history.
      Two established predictors of violence, a history of arrests and substance abuse,
      are unreliable when assessed by self-report.

PMID- 14645806
TI  - An administrator's perspective on mental health in assisted living.
AB  - Administrators of 94 assisted living facilities in Michigan completed a 19-item
      survey about the extent of mental health problems of residents and how such
      problems were addressed. In 45 facilities more than half of the residents were
      reported to be cognitively impaired. The two most common problems were dementia
      and depression. The most common problematic behaviors were resistance to care and
      wandering. Two-thirds of the facilities conducted some type of mental health
      evaluation at admission, and two-thirds conducted evaluations as needed. The most
      common treatment barriers were patient refusal and family refusal. Results of the
      study suggest that there may be a significant need for mental health services in
      assisted living facilities.

PMID- 14645805
TI  - Volume of VA patients with posttraumatic stress disorder in the New York
      metropolitan area after September 11.
AB  - The authors examined data from the Veterans Integrated Service Network of New
      York and New Jersey to determine whether the number of veterans who were treated
      for posttraumatic stress disorder (PTSD) increased significantly after the
      terrorist attacks of September 11, 2001. They analyzed the number of veterans
      treated for PTSD at Veterans Healthcare Administration facilities in New York and
      New Jersey from September 1999 through June 2002. The number of veterans treated
      for PTSD in these facilities after September 11 exceeded projections based on
      secular trends, and the increase was more pronounced than for other diagnostic
      groups. The results highlight the need to ensure adequate availability of
      services in the wake of traumatic events.

PMID- 14645807
TI  - A quality improvement process for implementing the Texas algorithm for
      schizophrenia in Ohio.
AB  - Medication algorithms developed in Texas are being implemented in a number of
      states in the United States and internationally. This report describes a quality
      improvement process adapted from the Texas Medication Algorithm Project that was
      used to implement the Texas algorithm for schizophrenia in Ohio. A total of 38
      physicians were surveyed about their perceptions of barriers to implementation of
      the guidelines. The physicians generally thought that the schizophrenia algorithm
      was good, current, and applicable. Although they did not perceive barriers to its
      implementation, they did not seem to alter their practices to a great extent in
      response to the algorithm. The results of the study may guide other states in
      their implementation of algorithms.

PMID- 14645808
TI  - Near-death experiences in a psychiatric outpatient clinic population.
AB  - Near-death experiences, or mystical experiences during encounters with death, are
      reported to have beneficial effects despite their phenomenologic similarity to
      pathological states. This study explored the prevalence of near-death experiences
      and associated psychological distress by using a cross-sectional survey of 832
      psychiatric outpatients. Standardized measures of near-death experiences and
      psychological distress were administered via questionnaire at clinic intake. A
      total of 272 patients (33 percent) reported encounters with death, and these
      patients were found to have greater psychological distress than other patients.
      Sixty-one of the patients who had been close to death (22 percent) reported
      having near-death experiences, and these patients were found to have less
      psychological distress than patients who did not have near-death experiences
      after brushes with death.

PMID- 14645810
TI  - Potential synergy: voltage-driven steps in receptor-G protein coupling and
      beyond.
AB  - G protein-coupled receptor responses are not generally considered to show voltage
      dependence, but recently, the sensitivity of an oocyte to acetylcholine, which
      activates the m2 subtype of muscarinic receptors, was shown to be affected by
      changes in the membrane potential. Another example is the m2 receptor-evoked
      cation current in mammalian smooth muscle cells, which shows strong voltage
      dependence even when the receptor is bypassed by activating the G protein
      directly by intracellular application of GTPgammaS, a hydrolysis-resistant
      guanosine triphosphate (GTP) analog. Even among the few examples of voltage
      dependent behavior known from among the plethora of G protein-coupled responses,
      the mechanism underlying the voltage dependence seems to differ.

PMID- 14645811
TI  - Spine-tingling excitement from glutamate receptors.
AB  - Ionotropic glutamate receptors excite nerve cells by forming cation-selective
      pores in the membrane. Recent work, however, provides evidence that atypical
      signaling by glutamate receptors regulates the production and maintenance of
      dendritic spines, the short outgrowths that receive most central excitatory
      synapses. The control of spine formation involves the amino-terminal
      extracellular domain of the GluR2 subunit of AMPA (alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid) receptors. How interactions with this domain
      elicit signals to downstream effectors remains to be elucidated, but ion flux
      through the channel may not be required. This Perspective discusses the
      possibility that regulation of spines by GluR2 may be one of a growing collection
      of cases in which ionotropic glutamate receptors can elicit biochemical changes
      that are conventionally attributed to metabotropic receptors. It is suggested
      that proteins in contact with specific glutamate receptor subunits may directly
      sense the conformational changes produced by agonist binding.

PMID- 14645812
TI  - Don't let ideology trump science.

PMID- 14645814
TI  - Prestige wreck. For Spain, oil spill disaster is in the bag.

PMID- 14645813
TI  - French research. One-two punch leaves physicists gasping for breath.

PMID- 14645815
TI  - Primate research. Cambridge center wins a round.

PMID- 14645816
TI  - U.S. science policy. Nobelists go four-on-one with Cheney.

PMID- 14645817
TI  - Marine mammals. Military wins changes that may ease research.

PMID- 14645818
TI  - Microbiology. Triple-threat microbe gained powers from another bug.

PMID- 14645819
TI  - Condensed matter physics. Inverse Doppler demonstration ends a 60-year quest.

PMID- 14645821
TI  - Solar physics. Polar storms reboot the sun's magnetic program.

PMID- 14645820
TI  - Linguistics. Early date for the birth of Indo-European languages.

PMID- 14645822
TI  - Planetary science. Sweeping up after the solar system.

PMID- 14645823
TI  - Bioterrorism. Anthrax powder: state of the art?

PMID- 14645824
TI  - High-energy physics. To B or not to B?

PMID- 14645825
TI  - Loren Rieseberg profile. No garden-variety biologist.

PMID- 14645826
TI  - Causes of coral reef degradation.

PMID- 14645827
TI  - Bio2010 misinterpreted?

PMID- 14645828
TI  - Phylogeny of the SARS coronavirus.

PMID- 14645829
TI  - Education. Teaching in a research context.

PMID- 14645830
TI  - Physiology. Fish 'n flag.

PMID- 14645831
TI  - Atmospheric science. Nitrogen and climate change.

PMID- 14645832
TI  - Structural biology. Nuclear trafficking.

PMID- 14645833
TI  - Ocean science. The many shades of ocean blue.

PMID- 14645834
TI  - Immunology. The paracaspase connection.

PMID- 14645835
TI  - Cell biology. Eat me or die.

PMID- 14645836
TI  - Are we ready for pandemic influenza?
AB  - During the past year, the public has become keenly aware of the threat of
      emerging infectious diseases with the global spread of severe acute respiratory
      syndrome (SARS), the continuing threat of bioterrorism, the proliferation of West
      Nile virus, and the discovery of human cases of monkeypox in the United States.
      At the same time, an old foe has again raised its head, reminding us that our
      worst nightmare may not be a new one. In 2003, highly pathogenic strains of avian
      influenza virus, including the H5N1 and H7N7 subtypes, again crossed from birds
      to humans and caused fatal disease. Direct avian-to-human influenza transmission
      was unknown before 1997. Have we responded to these threats by better preparing
      for emerging disease agents, or are we continuing to act only as crises arise?
      Here we consider progress to date in preparedness for an influenza pandemic and
      review what remains to be done. We conclude by prioritizing the remaining needs
      and exploring the reasons for our current lack of preparedness for an influenza
      pandemic.

PMID- 14645837
TI  - Global freshwater resources: soft-path solutions for the 21st century.
AB  - Twentieth-century water policies relied on the construction of massive
      infrastructure in the form of dams, aqueducts, pipelines, and complex centralized
      treatment plants to meet human demands. These facilities brought tremendous
      benefits to billions of people, but they also had serious and often unanticipated
      social, economical, and ecological costs. Many unsolved water problems remain,
      and past approaches no longer seem sufficient. A transition is under way to a
      "soft path" that complements centralized physical infrastructure with lower cost
      community-scale systems, decentralized and open decision-making, water markets
      and equitable pricing, application of efficient technology, and environmental
      protection.

PMID- 14645838
TI  - Energy resources and global development.
AB  - In order to address the economic and environmental consequences of our global
      energy system, we consider the availability and consumption of energy resources.
      Problems arise from our dependence on combustible fuels, the environmental risks
      associated with their extraction, and the environmental damage caused by their
      emissions. Yet no primary energy source, be it renewable or nonrenewable, is free
      of environmental or economic limitations. As developed and developing economies
      continue to grow, conversion to and adoption of environmentally benign energy
      technology will depend on political and economic realities.

PMID- 14645839
TI  - Removing protected populations to save endangered species.

PMID- 14645840
TI  - Observation of the inverse Doppler effect.
AB  - We report experimental observation of an inverse Doppler shift, in which the
      frequency of a wave is increased on reflection from a receding boundary. This
      counterintuitive effect has been produced by reflecting a wave from a moving
      discontinuity in an electrical transmission line. Doppler shifts produced by this
      system can be varied in a reproducible manner by electronic control of the
      transmission line and are typically five orders of magnitude greater than those
      produced by solid objects with kinematic velocities. Potential applications
      include the development of tunable and multifrequency radiation sources.

PMID- 14645841
TI  - Attosecond synchronization of high-harmonic soft x-rays.
AB  - Subfemtosecond light pulses can be obtained by superposing several high harmonics
      of an intense laser pulse. Provided that the harmonics are emitted
      simultaneously, increasing their number should result in shorter pulses. However,
      we found that the high harmonics were not synchronized on an attosecond time
      scale, thus setting a lower limit to the achievable x-ray pulse duration. We
      showed that the synchronization could be improved considerably by controlling the
      underlying ultrafast electron dynamics, to provide pulses of 130 attoseconds in
      duration. We discuss the possibility of achieving even shorter pulses, which
      would allow us to track fast electron processes in matter.

PMID- 14645842
TI  - Molecular memories that survive silicon device processing and real-world
      operation.
AB  - If molecular components are to be used as functional elements in place of the
      semiconductor-based devices present in conventional microcircuitry, they must
      compete with semiconductors under the extreme conditions required for processing
      and operating a practical device. Herein, we demonstrate that porphyrin-based
      molecules bound to Si(100), which exhibit redox behavior useful for information
      storage, can meet this challenge. These molecular media in an inert atmosphere
      are stable under extremes of temperature (400 degrees C) for extended periods
      (approaching 1 hour) and do not degrade under large numbers of read-write cycles
      (10(12)).

PMID- 14645843
TI  - Structure-based carbon nanotube sorting by sequence-dependent DNA assembly.
AB  - Wrapping of carbon nanotubes (CNTs) by single-stranded DNA (ssDNA) was found to
      be sequence-dependent. A systematic search of the ssDNA library selected a
      sequence d(GT)n, n = 10 to 45 that self-assembles into a helical structure around
      individual nanotubes in such a way that the electrostatics of the DNA-CNT hybrid
      depends on tube diameter and electronic properties, enabling nanotube separation
      by anion exchange chromatography. Optical absorption and Raman spectroscopy show
      that early fractions are enriched in the smaller diameter and metallic tubes,
      whereas late fractions are enriched in the larger diameter and semiconducting
      tubes.

PMID- 14645844
TI  - Oceanic Rossby waves acting as a "hay rake" for ecosystem floating by-products.
AB  - Recent satellite observations of Rossby waves and chlorophyll anomalies
      propagating in subtropical gyres have suggested that wave-induced upwelling could
      stimulate photosynthesis. Instead, we show that chlorophyll maxima are located in
      abnormally warm water, in Rossby wave-induced convergences. This excludes inputs
      of nutrients from deeper water. We argue that the sea color anomalies are not
      caused by chlorophyll but by floating particles evolved from the ecosystem and
      accumulated by Rossby waves, acting as "marine hay rakes," in convergence zones.
      Such processes may be determinant for the distribution of living organisms in
      oligotrophic areas.

PMID- 14645845
TI  - Carbon in Amazon forests: unexpected seasonal fluxes and disturbance-induced
      losses.
AB  - The net ecosystem exchange of carbon dioxide was measured by eddy covariance
      methods for 3 years in two old-growth forest sites near Santarem, Brazil. Carbon
      was lost in the wet season and gained in the dry season, which was opposite to
      the seasonal cycles of both tree growth and model predictions. The 3-year average
      carbon loss was 1.3 (confidence interval: 0.0 to 2.0) megagrams of carbon per
      hectare per year. Biometric observations confirmed the net loss but imply that it
      is a transient effect of recent disturbance superimposed on long-term balance.
      Given that episodic disturbances are characteristic of old-growth forests, it is
      likely that carbon sequestration is lower than has been inferred from recent eddy
      covariance studies at undisturbed sites.

PMID- 14645846
TI  - High deleterious genomic mutation rate in stationary phase of Escherichia coli.
AB  - In natural habitats, bacteria spend most of their time in some form of growth
      arrest. Little is known about deleterious mutations in such stages, and
      consequently there is limited understanding of what evolutionary events occur. In
      a deleterious mutation accumulation experiment in prolonged stationary phase of
      Escherichia coli, about 0.03 slightly deleterious mutations were observed per
      genome per day. This is over an order of magnitude higher than extrapolations
      from fast-growing cells, but in line with inferences from observations in
      adaptive stationary phase mutation experiments. These findings may affect
      understanding of bacterial evolution and the emergence of bacterial
      pathogenicity.

PMID- 14645847
TI  - Phosphatidylserine receptor is required for clearance of apoptotic cells.
AB  - Cells undergoing apoptosis during development are removed by phagocytes, but the
      underlying mechanisms of this process are not fully understood. Phagocytes
      lacking the phosphatidylserine receptor (PSR) were defective in removing
      apoptotic cells. Consequently, in PSR-deficient mice, dead cells accumulated in
      the lung and brain, causing abnormal development and leading to neonatal
      lethality. A fraction of PSR knockout mice manifested a hyperplasic brain
      phenotype resembling that of mice deficient in the cell death-associated genes
      encoding Apaf-1, caspase-3, and caspase-9, which suggests that phagocytes may
      also be involved in promoting apoptosis. These data demonstrate a critical role
      for PSR in early stages of mammalian organogenesis and suggest that this receptor
      may be involved in respiratory distress syndromes and congenital brain
      malformations.

PMID- 14645848
TI  - Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through
      CED-5 and CED-12.
AB  - During apoptosis, phosphatidylserine, which is normally restricted to the inner
      leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and
      has been suggested to act as an "eat-me" signal to trigger phagocytosis. It is
      unclear how phagocytes recognize phosphatidylserine. Recently, a putative
      phosphatidylserine receptor (PSR) was identified and proposed to mediate
      recognition of phosphatidylserine and phagocytosis. We report that psr-1, the
      Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment.
      In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed
      phosphatidylserine. In C. elegans, PSR-1 acts in the same cell corpse engulfment
      pathway mediated by intracellular signaling molecules CED-2 (homologous to the
      human CrkII protein), CED-5 (DOCK180), CED-10 (Rac GTPase), and CED-12 (ELMO),
      possibly through direct interaction with CED-5 and CED-12. Our findings suggest
      that PSR-1 is likely an upstream receptor for the signaling pathway containing
      CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in
      recognizing phosphatidylserine during phagocytosis.

PMID- 14645849
TI  - Fish exploiting vortices decrease muscle activity.
AB  - Fishes moving through turbulent flows or in formation are regularly exposed to
      vortices. Although animals living in fluid environments commonly capture energy
      from vortices, experimental data on the hydrodynamics and neural control of
      interactions between fish and vortices are lacking. We used quantitative flow
      visualization and electromyography to show that trout will adopt a novel mode of
      locomotion to slalom in between experimentally generated vortices by activating
      only their anterior axial muscles. Reduced muscle activity during vortex
      exploitation compared with the activity of fishes engaged in undulatory swimming
      suggests a decrease in the cost of locomotion and provides a mechanism to
      understand the patterns of fish distributions in schools and riverine
      environments.

PMID- 14645850
TI  - Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus
      aureus.
AB  - Vancomycin is usually reserved for treatment of serious infections, including
      those caused by multidrug-resistant Staphylococcus aureus. A clinical isolate of
      S. aureus with high-level resistance to vancomycin (minimal inhibitory
      concentration = 1024 microg/ml) was isolated in June 2002. This isolate harbored
      a 57.9-kilobase multiresistance conjugative plasmid within which Tn1546 (vanA)
      was integrated. Additional elements on the plasmid encoded resistance to
      trimethoprim (dfrA), beta-lactams (blaZ), aminoglycosides (aacA-aphD), and
      disinfectants (qacC). Genetic analyses suggest that the long-anticipated transfer
      of vancomycin resistance to a methicillin-resistant S. aureus occurred in vivo by
      interspecies transfer of Tn1546 from a co-isolate of Enterococcus faecalis.

PMID- 14645851
TI  - The structure of importin-beta bound to SREBP-2: nuclear import of a
      transcription factor.
AB  - The sterol regulatory element-binding protein 2 (SREBP-2), a nuclear
      transcription factor that is essential for cholesterol metabolism, enters the
      nucleus through a direct interaction of its helix-loop-helix leucine zipper
      domain with importin-beta. We show the crystal structure of importin-beta
      complexed with the active form of SREBP-2. Importin-beta uses characteristic long
      helices like a pair of chopsticks to interact with an SREBP-2 dimer. Importin
      beta changes its conformation to reveal a pseudo-twofold symmetry on its surface
      structure so that it can accommodate a symmetric dimer molecule. Importin-beta
      may use a similar strategy to recognize other dimeric cargoes.

PMID- 14645852
TI  - Notch-mediated restoration of regenerative potential to aged muscle.
AB  - A hallmark of aging is diminished regenerative potential of tissues, but the
      mechanism of this decline is unknown. Analysis of injured muscle revealed that,
      with age, resident precursor cells (satellite cells) had a markedly impaired
      propensity to proliferate and to produce myoblasts necessary for muscle
      regeneration. This was due to insufficient up-regulation of the Notch ligand
      Delta and, thus, diminished activation of Notch in aged, regenerating muscle.
      Inhibition of Notch impaired regeneration of young muscle, whereas forced
      activation of Notch restored regenerative potential to old muscle. Thus, Notch
      signaling is a key determinant of muscle regenerative potential that declines
      with age.

PMID- 14645853
TI  - Mutation of MEF2A in an inherited disorder with features of coronary artery
      disease.
AB  - The early genetic pathway(s) triggering the pathogenesis of coronary artery
      disease (CAD) and myocardial infarction (MI) remain largely unknown. Here, we
      describe an autosomal dominant form of CAD/MI (adCAD1) that is caused by the
      deletion of seven amino acids in transcription factor MEF2A. The deletion
      disrupts nuclear localization of MEF2A, reduces MEF2A-mediated transcription
      activation, and abolishes synergistic activation by MEF2A and by the
      transcription factor GATA-1 through a dominant-negative mechanism. The MEF2A
      protein demonstrates strong expression in the endothelium of coronary arteries.
      These results identify a pathogenic gene for a familial vascular disease with
      features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of
      CAD/MI.

PMID- 14645854
TI  - ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin
      remodeling complex.
AB  - The conserved histone variant H2AZ has an important role in the regulation of
      gene expression and the establishment of a buffer to the spread of silent
      heterochromatin. How histone variants such as H2AZ are incorporated into
      nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related
      adenosine triphosphatase, is the catalytic core of a multisubunit, histone
      variant exchanger that efficiently replaces conventional histone H2A with histone
      H2AZ in nucleosome arrays. Swr1 is required for the deposition of histone H2AZ at
      specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a
      subset of yeast genes. These findings define a previously unknown role for the
      adenosine triphosphate-dependent chromatin remodeling machinery.

PMID- 14645855
TI  - Aligned multiwalled carbon nanotube membranes.
AB  - An array of aligned carbon nanotubes (CNTs) was incorporated across a polymer
      film to form a well-ordered nanoporous membrane structure. This membrane
      structure was confirmed by electron microscopy, anisotropic electrical
      conductivity, gas flow, and ionic transport studies. The measured nitrogen
      permeance was consistent with the flux calculated by Knudsen diffusion through
      nanometer-scale tubes of the observed microstructure. Data on Ru(NH3)6(3+)
      transport across the membrane in aqueous solution also indicated transport
      through aligned CNT cores of the observed microstructure. The lengths of the
      nanotubes within the polymer film were reduced by selective electrochemical
      oxidation, allowing for tunable pore lengths. Oxidative trimming processes
      resulted in carboxylate end groups that were readily functionalized at the
      entrance to each CNT inner core. Membranes with CNT tips that were functionalized
      with biotin showed a reduction in Ru(NH3)6(3+) flux by a factor of 15 when bound
      with streptavidin, thereby demonstrating the ability to gate molecular transport
      through CNT cores for potential applications in chemical separations and sensing.

PMID- 14645857
TI  - Rising expectations.

PMID- 14645856
TI  - BAR domains as sensors of membrane curvature: the amphiphysin BAR structure.
AB  - The BAR (Bin/amphiphysin/Rvs) domain is the most conserved feature in
      amphiphysins from yeast to human and is also found in endophilins and nadrins. We
      solved the structure of the Drosophila amphiphysin BAR domain. It is a crescent
      shaped dimer that binds preferentially to highly curved negatively charged
      membranes. With its N-terminal amphipathic helix and BAR domain (N-BAR),
      amphiphysin can drive membrane curvature in vitro and in vivo. The structure is
      similar to that of arfaptin2, which we find also binds and tubulates membranes.
      From this, we predict that BAR domains are in many protein families, including
      sorting nexins, centaurins, and oligophrenins. The universal and minimal BAR
      domain is a dimerization, membrane-binding, and curvature-sensing module.

PMID- 14645858
TI  - Linking development and aging.
AB  - Evolutionary theory predicts that the different life stages of organisms are
      coordinated to achieve maximal reproductive output. Moreover, aging can be seen
      as an evolutionary side effect of this selective process that applies to many
      living organisms. Hence, genetic, developmental, and physiological mechanisms
      resulting from this selection are expected to be conserved in diverse lineages.
      The insulin/insulin-like growth factor signaling (INS) pathway appears to be such
      a mechanism that regulates life span and reproduction in a variety of model
      organisms. Here I argue that the experimental tools of environmental manipulation
      and gene by environment interaction should be used more often both during the
      experimental organism's development and its adult life. This approach will help
      us to fully understand the functions of longevity-determining pathways and will
      determine the life stages during which these pathways exert their effects on
      adult life. These points are raised because of a recent Aging Cell publication by
      Tu and Tatar, in which the larval food environment was manipulated to determine
      the effects on adult reproduction, life span, aging, and INS. The results of this
      study are a promise of the usefulness of this approach for understanding the
      aging process.

PMID- 14645859
TI  - Early diagnosis of pyomyositis using clinic-based ultrasonography in a patient
      receiving infliximab therapy for Behcet's disease.

PMID- 14645860
TI  - Aphonia as a rare prodromal symptom in a case of Churg-Strauss syndrome with
      coincident coeliac disease.

PMID- 14645861
TI  - Polymyositis associated with infliximab treatment for rheumatoid arthritis.

PMID- 14645862
TI  - Specific autoantibodies of SLE, such as anti-Ku, anti-ribosome Po and anti
      membrane DNA autoantibodies, in a case of human African trypanosomiasis.

PMID- 14645864
TI  - Arthrocentesis in the past. Comment on an article by Aceves-Avila et al.

PMID- 14645865
TI  - Cutaneous childhood sarcoidosis--a rare disease refractory to treatment.

PMID- 14645866
TI  - Suicides in persons suffering from rheumatoid arthritis.

PMID- 14645868
TI  - Infliximab cost-effectiveness/safety?

PMID- 14645870
TI  - Optimistic assumptions in modelling studies have a substantial influence on the
      cost-effectiveness result.

PMID- 14645871
TI  - Dysphagia associated with lower thoracic spondylosis.

PMID- 14645872
TI  - Methotrexate for rheumatoid arthritis: what should the patient be told?

PMID- 14645873
TI  - A fatal case of pleural osteosarcoma mimicking mesothelioma in Paget's disease of
      bone.

PMID- 14645875
TI  - Percutaneous radiofrequency ablation for inoperable non-small cell lung cancer
      and metastases: preliminary report.
AB  - PURPOSE: To assess technical feasibility, efficacy, and complications of
      percutaneous computed tomography (CT)-guided transthoracic radiofrequency (RF)
      ablation for treating inoperable non-small cell lung cancer (NSCLC) and lung
      metastases. MATERIALS AND METHODS: Twenty-six patients with 27 NSCLCs and four
      patients with five lung metastases underwent RF ablation with cooled-tip
      electrodes with CT guidance. Patients were not candidates for surgery because of
      either advanced-stage disease (n = 20) and/or comorbid processes (n = 4) or
      refusal to undergo surgery (n = 6). The procedure was performed with the intent
      to cure in 10 (33%) patients with stage I tumors and as palliative therapy in 20
      (67%) patients. Contrast material-enhanced CT was performed immediately, 1 month,
      and then every 3 months after RF ablation to evaluate the response to therapy.
      Time to death for each patient was calculated with Kaplan-Meier analysis, and the
      effect of tumor size and the extent of coagulation necrosis on time to death were
      determined. RESULTS: Complete necrosis was attained in 12 (38%) of 32 lesions;
      partial (>50%) necrosis, in the remaining 20 (62%) lesions. Tumor size was a
      major discriminator in achieving complete necrosis. Complete necrosis was
      attained in all six (100%) tumors smaller than 3 cm but only in six (23%) of 26
      larger tumors (P <.05). Mean survival of patients with complete necrosis (19.7
      months) was significantly better than that of patients with partial necrosis (8.7
      months) (P <.01). There were three (in 30 patients, 10%) major complications,
      which included acute respiratory distress syndrome, and two pneumothoraces that
      required thoracostomy. CONCLUSION: RF ablation appears to be a safe and promising
      procedure for the treatment of inoperable NSCLC and metastases.

PMID- 14645876
TI  - Esophageal cancer staging with endoscopic MR imaging: pilot study.
AB  - The authors defined esophageal anatomy and evaluated esophageal cancer staging in
      a pilot group by comparing endoscopic magnetic resonance (MR) imaging results
      with pathologic and endoscopic ultrasonographic (US) results when available. A
      porcine esophagus, one volunteer, and 23 patients suspected of having esophageal
      cancer were imaged at 0.5 T. MR imaging was successful in 21 patients. Eight of
      these patients underwent esophagectomy (one after chemotherapy, which invalidated
      comparison with MR imaging; another did not undergo lymphadenectomy) and one
      underwent laparoscopy and nodal staging only; eight underwent US. When verified
      with pathologic staging, endoscopic MR imaging was accurate in six of seven
      patients (T stage) and five of six patients (N stage; nodal areas too obscured by
      artifact for comparison in one case). MR imaging and US results concurred in
      seven of eight (T stage) and five of eight (N stage) patients. No complications
      were observed. Endoscopic MR imaging is safe and probably comparable to
      endoscopic US, but with a tendency to overstage the disease.

PMID- 14645877
TI  - Biologic response to polymer-coated stents: in vitro analysis and results in an
      iliac artery sheep model.
AB  - PURPOSE: To evaluate biologic response to poly(hydroxymethyl-p-xylylene-co-p
      xylylene) (PHPX)-coated stents in vitro and in vivo in sheep. MATERIALS AND
      METHODS: Physical stability, hemocompatibility, and cytotoxicity of the coating
      were first assessed in vitro. Thirty-six self-expanding nitinol (Memotherm), 24
      stainless steel balloon-mounted (Palmaz), and 12 self-expanding nitinol (ZA)
      stents were coated with PHPX by using chemical vapor deposition polymerization.
      Seventy-two coated and 72 uncoated stents were placed into iliac arteries of 36
      sheep. Sheep were classified into three groups of 12 animals each. In each group,
      six sheep were killed after 1 month; six, after 6 months. In each sheep, two
      uncoated stents were placed into one limb; two coated stents of the same type,
      into the opposite limb. In groups 1 and 2, Palmaz and Memotherm stents were used;
      in group 3, Memotherm and ZA stents were used. In groups 1 and 3, arteries were
      healthy. In group 2, arteries were pretreated with a Fogarty maneuver. Stent
      patency was measured with intravascular ultrasonography (US) and histologic
      analysis. Cellular response to coated and uncoated stents was assessed.
      Measurements were compared (Wilcoxon test). RESULTS: In vitro, PHPX coating was
      stable; hemocompatibility and cytotoxicity were similar to those of stainless
      steel. In vivo, patency of coated and uncoated Palmaz and ZA stents was not
      different (P >.05). Patency of coated and uncoated Memotherm stents did not
      differ in four of six follow-up subgroups, but it was significantly reduced in
      group 2 after 6 months (intravascular US, P =.03; histologic analysis, P =.01)
      and in group 3 after 1 month (histologic analysis, P =.01). Histologically, the
      cellular response to coated and uncoated stents was not different (P >.05).
      CONCLUSION: PHPX coating had good physical stability and biocompatibility in
      vitro and in vivo. Performance of coated and uncoated Palmaz and ZA stents was
      similar. Patency of Memotherm stents was similar in four of six follow-up
      subgroups. Materials effects did not result in severely enhanced neointimal
      hyperplasia.

PMID- 14645878
TI  - Percutaneous US-guided radiofrequency ablation with perfused needle applicators:
      improved survival with the VX2 tumor model in rabbits.
AB  - PURPOSE: To evaluate survival, metastases, tumor necrosis, and prediction of
      local recurrence after percutaneous ultrasonographically (US) guided
      radiofrequency (RF) thermal ablation with electrodes perfused continuously with
      isotonic saline. MATERIALS AND METHODS: VX2 liver tumors were implanted in 31
      rabbits according to a standardized protocol. After 21 days, 16 animals were
      treated percutaneously with RF ablation. Four animals died of complications
      related to anesthesia, and 12 animals were evaluated. All animals were followed
      for 110 days and monitored with computed tomography (CT) and US at 1, 7, and 30
      days. A control group of 15 animals did not receive treatment. Autopsy was
      performed at the end of scheduled follow-up or immediately after death. For
      survival analysis, the Kaplan-Meier method was used; for nominal data, the Fisher
      exact test was used. RESULTS: In comparison to controls, animals in the treatment
      group showed significantly prolonged survival (P <.001). Eight of 12 animals
      (67%) treated with RF ablation survived to 110 days, while none of the controls
      did so. Metastases developed in all controls (100%) and in eight of 12 treated
      animals (67%) (P =.001). In comparison with controls, animals that developed
      metastases despite treatment also showed significantly prolonged survival (P
      =.02). Local recurrence was observed in three of 12 animals (25%) in the
      treatment group. CT and US performed 1 week after treatment did not allow
      prediction of local recurrence. CONCLUSION: RF ablation of liver tumors with
      perfused needle applicators prolongs survival in the VX2 rabbit liver tumor
      model, regardless of whether complete remission is achieved. In comparison with
      controls, RF ablation results in a lower frequency of metastases.

PMID- 14645879
TI  - Asymptomatic radiation-induced telangiectasia in children after cranial
      irradiation: frequency, latency, and dose relation.
AB  - PURPOSE: To determine the frequency, dose relation, and latency of radiation
      induced telangiectasias in children after cranial irradiation. MATERIALS AND
      METHODS: The authors identified 90 children who had undergone cranial irradiation
      between 1981 and 2001 and undergone magnetic resonance (MR) imaging with follow
      up for at least 6 months. Patients were assigned to low-dose (LD) and high-dose
      (HD) groups. All 24 children in the LD group received a radiation dose of 18.0 or
      19.8 Gy. The 66 patients in the HD group received a dose of 32.0 Gy or greater.
      Telangiectasias were defined as small low-signal-intensity foci on intermediate-
      or T2-weighted MR images. For the patients who underwent serial MR imaging, the
      first depicted appearance of each telangiectatic lesion was recorded. Statistical
      analyses were performed. RESULTS: Telangiectasias in at least one area were
      observed in 18 (20%) patients. The frequency of telangiectasia was 13% (three of
      24 patients) in the LD group as compared with 23% (15 of 66 patients) in the HD
      group; this difference was not significant (P =.22, Fisher exact test). In 12
      patients (one from LD and 11 from HD group) who underwent serial MR imaging
      follow-up for up to 10 years (mean, 8.1 years), a total of 31 lesions were
      detected. Twelve (39%) of these lesions were detected by the 3rd year, and 21
      (68%) were evident by the 5th year. Six (50%) of the 12 patients who underwent
      serial MR imaging had telangiectatic foci after 5 years. CONCLUSION: Radiation
      induced telangiectasia appears to occur in at least 20% of children who undergo
      cranial irradiation. In this small series, higher radiation dose was not
      significantly associated with higher frequency of telangiectasia, although there
      was a trend in this direction.

PMID- 14645880
TI  - Azygos arch valves: prevalence and appearance at contrast-enhanced CT.
AB  - PURPOSE: To evaluate the prevalence and appearance of azygos arch valves at
      intravenous contrast material-enhanced computed tomography (CT). MATERIALS AND
      METHODS: Findings of 309 intravenous contrast-enhanced spiral CT examinations of
      the chest were retrospectively reviewed. The presence of contrast material reflux
      into the azygos arch and of a focal bulge in the azygos arch was recorded. An
      azygos valve was considered present if contrast material with a curvilinear
      posterior contour was seen in the azygos arch. The chi2 test was used to compare
      the frequency of contrast material reflux into the azygos vein for high and low
      rates of contrast material injection and for right and left arm injection.
      RESULTS: Reflux of contrast material into the azygos arch occurred at 154 (49.8%)
      of 309 examinations, and valves were seen on images of 105 (68.2%) examinations.
      A focal bulge was seen in the azygos arch on images of 86 (81.9%) of 105
      examinations with an azygos valve. Contrast material refluxed more frequently
      into the azygos vein in examinations with high rates of injection (83 of 128
      examinations, 64.8%) than in those with low rates of injection (71 of 181, 39.2%,
      P <.001). Among the patients with high rates of injection, contrast material
      refluxed more frequently into the azygos vein with the right arm injection than
      with left arm injection (53 of 70, 76% vs 30 of 58, 52%, P <.01). Refluxed
      contrast material appeared as discrete collections within cusps of the azygos
      valves on images of 69 (44.8%) of 154 examinations. CONCLUSION: Valves in the
      azygos arch are common and more frequently seen at CT when high injection rates
      and right arm injections are used.

PMID- 14645881
TI  - Evaluation of lung injury after three-dimensional conformal stereotactic
      radiation therapy for solitary lung tumors: CT appearance.
AB  - PURPOSE: To evaluate the computed tomographic (CT) appearance of tumors and lung
      injury in patients who have undergone stereotactic radiation therapy (SRT) for
      solitary lung tumors. MATERIALS AND METHODS: Twenty-seven patients with primary
      lung cancer and four with metastatic lung cancer who underwent SRT for solitary
      lung tumors were enrolled for evaluation. SRT was delivered by using a three
      dimensional conformal technique with a stereotactic body frame. A total dose of
      48 Gy was administered in four fractions during a period of 2 weeks. After SRT,
      follow-up CT images were obtained every 2-3 months. Radiation-induced pulmonary
      injuries were classified into four patterns on CT images. The minimal lung dose
      to areas demonstrating pulmonary injury at CT was evaluated, and the correlation
      between the dose and the percentage volume of the whole lung irradiated by more
      than 20 Gy in total (V20) was assessed by using Spearman rank correlation.
      RESULTS: Tumor shrinkage continued for 2-15 months after SRT. Asymptomatic
      changes in the irradiated lung were noted at CT in all patients within 2-6 months
      (median, 4 months) after SRT. As the pattern at pulmonary CT changed, patchy
      consolidation was more predominantly seen as an acute change than were slight
      homogeneous increase in opacity, discrete consolidation, or solid consolidation;
      solid consolidation was the more predominantly seen late change. The minimal lung
      dose to the area demonstrating pulmonary injury in each patient ranged between 16
      and 36 Gy (median, 24 Gy). The dose was significantly (P <.001) inversely
      correlated with the V20 in each patient. CONCLUSION: The reaction to SRT of the
      lungs seems similar to the reaction to conventional radiation therapy.

PMID- 14645882
TI  - Glomerular filtration rate measured by using triphasic helical CT with a two
      point Patlak plot technique.
AB  - PURPOSE: To determine the accuracy of the two-point Patlak plot in the
      calculation of glomerular filtration rate (GFR). MATERIALS AND METHODS: Fifty
      patients without acute renal disorder were included. GFR was calculated by using
      a two-point Patlak plot technique. The computed tomography (CT) protocol
      consisted of a plain examination followed by two contrast material-enhanced
      examinations in the arterial and portovenous phase. Each examination included the
      entire kidneys and was performed after injection of 120 mL iopromide and 300 mg
      of iodine per milliliter given per 75 kg of body weight. All examinations were
      performed with a standard abdominal protocol. Section thickness was 4 x 2.5 mm,
      and table advance was 12.5 mm. Bolus triggering commenced 10 seconds after the
      start of contrast medium injection. Twelve dynamic scans were obtained with
      reduced tube current every 3 seconds to obtain sufficient arterial input function
      data. Correction for hematocrit level was made by using the unenhanced
      attenuation of the aorta. As a reference method, plasma clearance of the contrast
      medium injected for CT was calculated from three iodine plasma concentration
      measurements obtained 3, 4, and 5 hours after injection. Linear correlation was
      performed. RESULTS: GFR was calculated from CT data in 48 patients. Two patients
      were excluded because of breathing errors. Mean GFR was 80 mL/min (range, 17-153
      mL/min) as measured with iopromide plasma clearance and 82 mL/min (range, 28-148
      mL/min) as measured with CT. Linear correlation between the two methods was r =
      0.889; GFR calculated with the two-point Patlak plot was equal to 15 plus 0.83
      times GFR (plasma clearance). The mean difference between GFRs as determined with
      the two methods was -1.2 mL/min (95% CI: -27.1, 24.6). CONCLUSION: Total GFR can
      be measured accurately with minimally extended triphasic CT in patients without
      acute renal disorder by using a two-point Patlak plot technique.

PMID- 14645883
TI  - Multi-detector row spiral CT angiography of the thoracic outlet: dose reduction
      with anatomically adapted online tube current modulation and preset dose savings.
AB  - PURPOSE: To evaluate image quality obtained with anatomically adapted online tube
      current modulation and preset minimum dose savings at multi-detector row spiral
      computed tomographic (CT) angiography of the thoracic outlet. MATERIALS AND
      METHODS: A total of 100 patients were evaluated for thoracic outlet arterial
      syndrome with spiral CT angiography (collimation, 4 x 1 mm; pitch, 1.75) both
      with and without dose reduction by means of anatomically adapted online tube
      current modulation and preset minimum dose savings. Preset minimum savings of 20%
      and of 32% were applied in two groups of 50 patients (groups 1 and 2). In each
      group, low-dose scanning was performed in 25 patients in the neutral position and
      in 25 patients after postural maneuver. Tube current-time product, noise,
      presence and quality of graininess and of linear streak artifacts on transverse
      CT scans, and diagnostic value of sagittal reformations and volume-rendered
      images were evaluated and recorded for each data set. chi2 test was used to
      compare frequencies; paired Wilcoxon rank test, to compare subjective and
      objective image quality scores. P <.05 indicated a significant difference.
      RESULTS: In group 1, mean tube current-time product was 3225 mAs for reference
      scans and 2101 mAs for low-dose scans (mean reduction, 35%; range, 27%-47%). In
      group 2, mean was 3070 mAs for reference scans and 2068 mAs for low-dose scans
      (mean reduction, 33%; range, 17%-38%). In group 1, no differences in frequencies
      of graininess and linear streaking or in noise level were found between images
      acquired with or without dose reduction. In group 2, no difference was found in
      noise level between low-dose and reference scans. On low-dose scans, moderate
      linear streaking was observed with lower frequency and moderate graininess was
      observed with higher frequency, but artifacts did not compromise image quality or
      prevent confident assessment of arterial diameter in the three compartments of
      the thoracic outlet. CONCLUSION: Online tube current modulation with a preset
      minimum dose saving of 20% allowed 35% reduction in mean tube current-time
      product, with no loss in image quality.

PMID- 14645884
TI  - Image stacking with entropy values in conventional angiography: initial
      experience.
AB  - The entropy method for stacking a series of angiographic images is presented and
      compared with the maximum opacity method, which is already established. The
      entropy method comprises calculation of the entropy of the time course for each
      image pixel. This accentuates image areas where a contrast agent bolus is
      passing. Quantitative analysis of the contrast-to-noise ratio and qualitative
      analysis of 11 cases were performed, the latter by eight independent viewers.
      Results indicate that the entropy images show more vascular detail in small
      peripheral vessels and increased contrast-to-noise ratio by up to a factor of
      1.97 compared with maximum opacity images.

PMID- 14645885
TI  - Fiber tract-based atlas of human white matter anatomy.
AB  - Two- and three-dimensional (3D) white matter atlases were created on the basis of
      high-spatial-resolution diffusion tensor magnetic resonance (MR) imaging and 3D
      tract reconstruction. The 3D trajectories of 17 prominent white matter tracts
      could be reconstructed and depicted. Tracts were superimposed on coregistered
      anatomic MR images to parcel the white matter. These parcellation maps were then
      compared with coregistered diffusion tensor imaging color maps to assign visible
      structures. The results showed (a). which anatomic structures can be identified
      on diffusion tensor images and (b). where these anatomic units are located at
      each section level and orientation. The atlas may prove useful for educational
      and clinical purposes.

PMID- 14645886
TI  - Hereditary hemorrhagic telangiectasia: multi-detector row helical CT assessment
      of hepatic involvement.
AB  - PURPOSE: To describe findings obtained with multi-detector row helical computed
      tomography (CT) of the liver in patients with hereditary hemorrhagic
      telangiectasia. MATERIALS AND METHODS: Multiphasic multi-detector row helical CT
      was performed in 70 consecutive patients (29 females and 41 males; mean age, 48.5
      years; age range, 15-75 years): 64 considered to have hereditary hemorrhagic
      telangiectasia and six suspected of having the disease. Scanning delay was
      achieved by using a test bolus of contrast medium to obtain early arterial phase,
      late arterial phase, and portal venous phase images. Multiplanar and angiographic
      reconstructions were then generated. The presence of shunts, hepatic perfusion
      disorders, telangiectases, other vascular lesions, indirect signs of portal
      hypertension, and vascular anatomic variants were evaluated by two radiologists
      in consensus. RESULTS: Fifty-two of 70 (74%) patients had hepatic vascular
      abnormalities. Only four of 52 (8%) patients were symptomatic. Arterioportal
      shunts were present in 27 of 52 (52%) patients, arteriosystemic shunts in eight
      of 52 (15%), and both shunt types in 17 of 52 (33%). In 34 of 52 (65%) patients,
      parenchymal perfusion disorders were detected. Telangiectases were found in 33 of
      52 (63%) patients. Large confluent vascular masses were identified in 13 of 52
      (25%) patients. In 31 of 52 (60%) patients, indirect CT signs of portal
      hypertension were detected, but only one had clinical signs of this condition.
      Vascular anatomic variants were detected in seven patients (13%). CONCLUSION:
      Multi-detector row helical CT and reconstructions depict the complex hepatic
      vascular alterations typical of hereditary hemorrhagic telangiectasia.

PMID- 14645888
TI  - Organizing patient safety research to identify risks and hazards.
AB  - Patient safety has become an international priority with major research
      programmes being carried out in the USA, UK, and elsewhere. The challenge is how
      to organize research efforts that will produce the greatest yield in making
      health care safer for patients. Patient safety research initiatives can be
      considered in three different stages: (1) identification of the risks and
      hazards; (2) design, implementation, and evaluation of patient safety practices;
      and (3) maintaining vigilance to ensure that a safe environment continues and
      patient safety cultures remain in place. Clearly, different research methods and
      approaches are needed at each of the different stages of the continuum. A number
      of research approaches can be used at stage 1 to identify risks and hazards
      including the use of medical records and administrative record review, event
      reporting, direct observation, process mapping, focus groups, probabilistic risk
      assessment, and safety culture assessment. No single method can be universally
      applied to identify risks and hazards in patient safety. Rather, multiple
      approaches using combinations of these methods should be used to increase
      identification of risks and hazards of health care associated injury or harm to
      patients.

PMID- 14645889
TI  - The measurement of active errors: methodological issues.
AB  - The value of research in any topic area turns on its validity. Patient safety
      research has revealed--or, at least, given renewed urgency to--a raft of
      methodological issues. The meaning and thus the value of empirical research in
      this field is contingent on getting the methodology right. The need for good
      methods for the measurement of error is necessary whenever an inference is
      intended and, since inferences lie at the heart of research and management, there
      is a huge need to understand better how to make measurements that are meaningful,
      precise, and accurate. In this paper we consider issues relating to the
      measurement of error and the need for more research.

PMID- 14645890
TI  - The role of structured observational research in health care.
AB  - Structured observational research involves monitoring of healthcare domains by
      experts to collect data on errors, adverse events, near misses, team performance,
      and organisational culture. This paper describes some of the results of
      structured observational studies carried out in health care. It evaluates the
      strengths, weaknesses, and future challenges facing observational researchers by
      drawing lessons from the human factors and neonatal arterial switch operation
      (ASO) study in which two human factors specialists observed paediatric cardiac
      surgical procedures in 16 UK centres. Lessons learned from the ASO study are
      germane to other research teams embarking on studies that involve observational
      data collection. Future research needs robust observer training, clear measurable
      criteria to assess each researcher's domain knowledge, and observational
      competence. Measures of inter-rater reliability are needed where two or more
      observers participate in data collection. While it is important to understand the
      factors that lead to error and excellence among healthcare teams, it is also
      necessary to understand the characteristics of a good observer and the key types
      of error that can occur during structured observational studies like the human
      factors and ASO project.

PMID- 14645891
TI  - Safety culture assessment: a tool for improving patient safety in healthcare
      organizations.
AB  - Increasingly, healthcare organizations are becoming aware of the importance of
      transforming organizational culture in order to improve patient safety. Growing
      interest in safety culture has been accompanied by the need for assessment tools
      focused on the cultural aspects of patient safety improvement efforts. This paper
      discusses the use of safety culture assessment as a tool for improving patient
      safety. It describes the characteristics of culture assessment tools presently
      available and discusses their current and potential uses, including brief
      examples from healthcare organizations that have undertaken such assessments. The
      paper also highlights critical processes that healthcare organizations need to
      consider when deciding to use these tools.

PMID- 14645892
TI  - Finding clusters of similar events within clinical incident reports: a novel
      methodology combining case based reasoning and information retrieval.
AB  - A novel methodological approach for identifying clusters of similar medical
      incidents by analyzing large databases of incident reports is described. The
      discovery of similar events allows the identification of patterns and trends, and
      makes possible the prediction of future events and the establishment of barriers
      and best practices. Two techniques from the fields of information science and
      artificial intelligence have been integrated--namely, case based reasoning and
      information retrieval--and very good clustering accuracies have been achieved on
      a test data set of incident reports from transfusion medicine. This work suggests
      that clustering should integrate the features of an incident captured in
      traditional form based records together with the detailed information found in
      the narrative included in event reports.

PMID- 14645893
TI  - Assessing patient safety risk before the injury occurs: an introduction to
      sociotechnical probabilistic risk modelling in health care.
AB  - Since 1 July 2001 the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO) has required each accredited hospital to conduct at least
      one proactive risk assessment annually. Failure modes and effects analysis (FMEA)
      was recommended as one tool for conducting this task. This paper examines the
      limitations of FMEA and introduces a second tool used by the aviation and nuclear
      industries to examine low frequency, high impact events in complex systems. The
      adapted tool, known as sociotechnical probabilistic risk assessment (ST-PRA),
      provides an alternative for proactively identifying, prioritizing, and mitigating
      patient safety risk. The uniqueness of ST-PRA is its ability to model
      combinations of equipment failures, human error, at risk behavioral norms, and
      recovery opportunities through the use of fault trees. While ST-PRA is a complex,
      high end risk modelling tool, it provides an opportunity to visualize system risk
      in a manner that is not possible through FMEA.

PMID- 14645894
TI  - Methodology and rationale for the measurement of harm with trigger tools.
AB  - The growing recognition of harm as an unwelcome and frequently unrecognized
      byproduct of health care has initiated focused efforts to create highly reliable
      organizations for safe healthcare delivery. While debate continues over the exact
      magnitude of harm, there is a general acceptance of the need to improve our
      ability to deliver care in a safer manner. A major barrier to progress in safety
      has been the ability to effectively measure harm consistently and thus develop
      effective and targeted strategies to prevent its occurrence. This has resulted in
      a shift from initiatives focused exclusively on analysis of errors to those
      targeting events linked to harm. There is a growing recognition of a distinction
      between errors and adverse events as they often represent unique concepts
      fostering different strategies for improvement of safety. Conventional approaches
      to identifying and quantifying harm such as individual chart audits, incident
      reports, or voluntary administrative reporting have often been less successful in
      improving the detection of adverse events. As a result, a new method of measuring
      harm--the trigger tool--has been developed. It is easily customized and can be
      readily taught, enabling consistent and accurate measurement of harm. The
      history, application, and impact of the trigger tool concept in identifying and
      quantifying harm are discussed.

PMID- 14645895
TI  - Hindsight bias, outcome knowledge and adaptive learning.
AB  - The ubiquitous nature of hindsight bias is a cause for concern for those engaged
      in investigations and retrospective analysis of medical error. Hindsight does not
      equal foresight. Investigations that are anchored to outcome knowledge run the
      risk of not capturing the complexities and uncertainties facing sharp end
      personnel and why their actions made sense at the time. Important lessons go
      unlearned if the exercise is simply to back track someone else's decision
      landmarks. Outcome knowledge can also bias our thinking on the quality of the
      processes that led to the outcome. This paper examines the influence of outcome
      knowledge in relation to reconstructive memory and legal testimony, ways for
      reducing the impact of outcome knowledge, and an adaptive learning framework that
      places hindsight bias in a broader context of rapid updating of knowledge.

PMID- 14645896
TI  - Video techniques and data compared with observation in emergency trauma care.
AB  - Video recording is underused in improving patient safety and understanding
      performance shaping factors in patient care. We report our experience of using
      video recording techniques in a trauma centre, including how to gain cooperation
      of clinicians for video recording of their workplace performance, identify
      strengths of video compared with observation, and suggest processes for consent
      and maintenance of confidentiality of video records. Video records are a rich
      source of data for documenting clinician performance which reveal safety and
      systems issues not identified by observation. Emergency procedures and video
      records of critical events identified patient safety, clinical, quality
      assurance, systems failures, and ergonomic issues. Video recording is a powerful
      feedback and training tool and provides a reusable record of events that can be
      repeatedly reviewed and used as research data. It allows expanded analyses of
      time critical events, trauma resuscitation, anaesthesia, and surgical tasks. To
      overcome some of the key obstacles in deploying video recording techniques,
      researchers should (1) develop trust with video recorded subjects, (2) obtain
      clinician participation for introduction of a new protocol or line of
      investigation, (3) report aggregated video recorded data and use clinician
      reviews for feedback on covert processes and cognitive analyses, and (4) involve
      multidisciplinary experts in medicine and nursing.

PMID- 14645897
TI  - Administrative data based patient safety research: a critical review.
AB  - Administrative data are readily available, inexpensive, computer readable, and
      cover large populations. Despite coding irregularities and limited clinical
      details, administrative data supplemented by tools such as the Agency for
      Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs) could
      serve as a screen for potential patient safety problems that merit further
      investigation, offer valuable insights into adverse impacts and risks of medical
      errors and, to some extent, provide benchmarks for tracking progress in patient
      safety efforts at local, state, or national levels.

PMID- 14645898
TI  - How will we get the data and what will we do with it then? Issues in the
      reporting of adverse healthcare events.
AB  - Incident reporting has been proposed as an important means of identifying and
      addressing the causes of human error in medicine, and initiatives to implement
      these schemes have been set up in many countries. However, incident reporting has
      its limitations. Many people have been too ready to believe the overstated claims
      about the effectiveness of incident reporting in other domains. Others have not
      listened to the more limited claims made by the operators of existing systems in
      aviation and in organizational health and safety applications. This paper argues
      that more attention should be paid to the problems of eliciting incident reports
      from a broad spectrum of healthcare workers. It is also argued that more
      sophisticated computation support should be recruited so that clinicians do not
      have to learn complex command languages when they want to search for common
      factors in those incidents that are submitted.

PMID- 14645899
TI  - Organization of event reporting data for sense making and system improvement.
AB  - Feedback and demonstrable local usefulness are critical determinants for adopting
      event reporting by an organization. The classification schemes used by an
      organization determine whether an event is recognized or ignored. Near miss
      events, by their frequency and information content concerning recovery, merit
      recognition. "Just" cultures are learning cultures that provide a safe haven in
      which errors may be reported without the fear of disciplinary action in events
      without reckless behavior. As event report databases grow, selection and
      prioritization for in depth investigation become critical issues. Risk assessment
      tools and similarity matching approaches such as in case based reasoning are
      useful in this regard. Root cause analysis provides a framework for the
      collection, analysis, and trending of event data. The importance of both internal
      and external risk communication as valuable reporting system components may be
      overlooked.

PMID- 14645900
TI  - The immune control and cell-to-cell spread of human T-lymphotropic virus type 1.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) varies little in sequence compared
      with human immunodeficiency virus type 1 (HIV) and it is difficult to detect HTLV
      1 mRNA, proteins or virions in fresh blood. But the strong and chronically
      activated T cell response to the virus indicates that HTLV-1 proteins are
      expressed persistently. It now appears that the efficiency of an individual's
      cytotoxic T cell (CTL) response to HTLV-1 is the chief single determinant of that
      person's provirus load, which can differ between HTLV-1-infected people by more
      than 10 000-fold. Progress is now being made towards defining this CTL
      'efficiency' in terms of host genetics, T cell function, T cell gene expression
      and mathematical dynamics. Lymphocytes that are naturally infected with HTLV-1 do
      not produce enveloped extracellular virions in short-term culture and this has
      reinforced the erroneous conclusion that the virus is latent. But recent evidence
      shows that HTLV-1 can spread directly between lymphocytes across a specialized,
      virus-induced cell-cell contact - a 'viral synapse'. Instead of making
      extracellular virions, HTLV-1 uses the mobility of the host cell to spread within
      and between hosts. In this review the evidence is summarized on the persistent
      gene expression of HTLV-1 in vivo, the role of the immune system in protection
      and pathogenesis in HTLV-1 infection, and the mechanism of cell-to-cell spread of
      HTLV-1.

PMID- 14645901
TI  - Genetic variability of hepatitis A virus.
AB  - Knowledge of the molecular biology of hepatitis A virus (HAV) has increased
      exponentially since its identification. HAV exploits all known mechanisms of
      genetic variation to ensure survival, including mutation and genetic
      recombination. HAV has been characterized by the emergence of different
      genotypes, three human antigenic variants and only one major serotype. This paper
      reviews the genetic variability and molecular epidemiology of HAV. Its
      evolutionary mechanisms are described with particular emphasis on genetic
      recombination and HAV mutation rate. Genotypic classification methods are also
      discussed.

PMID- 14645902
TI  - Transcriptional activation of immediate-early gene ETR101 by human T-cell
      leukaemia virus type I Tax.
AB  - Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular
      gene expression through interactions with multiple cellular transcription
      pathways. This study describes the finding of immediate-early gene ETR101
      expression in HTLV-I-infected cells and its regulation by Tax. ETR101 was
      persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected
      cells. Expression of ETR101 was dependent upon Tax expression in the inducible
      Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected
      with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter in a
      transient transfection assay. A series of deletion and mutation analyses of the
      ETR101 gene promoter indicated that a 35 bp region immediately upstream of the
      TATA-box sequence, which contains a consensus cAMP response element (CRE) and a
      G+C-rich sequence, is the critical responsive element for Tax activation. Site
      directed mutagenesis analysis of the 35 bp region suggested that both the
      consensus CRE motif and its upstream G+C-rich sequence were critical for Tax
      transactivation. Electrophoretic mobility shift analysis (EMSA) using the 35 bp
      sequence as probe showed the formation of a specific protein-DNA complex in HTLV
      I-infected cell lines. EMSA with specific antibodies confirmed that the CREB
      transcription factor was responsible for formation of this specific protein-DNA
      complex. These results suggested that Tax directly transactivated ETR101 gene
      expression, mainly through a CRE sequence via the CREB transcription pathway.

PMID- 14645903
TI  - A novel cellular RNA helicase, RH116, differentially regulates cell growth,
      programmed cell death and human immunodeficiency virus type 1 replication.
AB  - In an effort to define novel cellular factors regulating human immunodeficiency
      virus type 1 (HIV-1) replication, a differential display analysis has been
      performed on endogenously infected cells stimulated with the HIV-suppressive
      immunomodulator Murabutide. In this study, the cloning and identification of a
      Murabutide-downregulated gene, named RH116, bearing classical motifs that are
      characteristic of the DExH family of RNA helicases, are reported. The 116 kDa
      encoded protein shares 99.9 % similarity with MDA-5, an inducible RNA helicase
      described recently. Ectopic expression of RH116 in HeLa-CD4 cells inhibited cell
      growth and cell proliferation but had no measurable effect on programmed cell
      death. RH116 presented steady state cytoplasmic localization and could
      translocate to the nucleus following HIV-1 infection. Moreover, the endogenous
      expression of RH116, at both the transcript and protein levels, was found to be
      considerably upregulated after infection. Overexpression of RH116 in HIV-1
      infected HeLa-CD4 cells also resulted in a dramatic increase in the level of
      secreted viral p24 protein. This enhancement in virus replication did not stem
      from upregulated proviral DNA levels but correlated with increased unspliced and
      singly spliced viral mRNA transcripts. These findings implicate RH116 in the
      regulation of HIV-1 replication and point to an apoptosis-independent role for
      this novel helicase in inducing cell growth arrest.

PMID- 14645904
TI  - Human immunodeficiency virus type 1 Vif supports efficient primate lentivirus
      replication in rhesus monkey cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus
      (SIV) Vif share limited homology and display species-specific activity, leading
      to speculation that Vif sequences could determine the block in HIV-1 replication
      in rhesus monkeys. To address this issue, we engineered a novel SIV recombinant
      in which HIV-1 vif replaced SIV vif in a SIVmac239 background. Insertion of HIV-1
      vif into the SIV vif locus did not produce a replication-competent virus.
      Therefore, we inserted HIV-1 vif sequences into the SIV nef locus, which produced
      a recombinant that, in the absence of SIV vif sequences, replicated similarly to
      wild-type SIVmac239 in rhesus monkey PBMC. From these studies we conclude that
      the HIV-1 replication block in rhesus monkeys is almost certainly not Vif
      determined. These studies also suggest that SHIV/NVif or derivative sequences
      could be utilized for structure/function studies of HIV-1 Vif in experimentally
      infected rhesus monkeys.

PMID- 14645905
TI  - Interference between avian endogenous ev/J 4.1 and exogenous ALV-J retroviral
      envelopes.
AB  - A new family of avian retroviral endogenous sequences designated ev/J or EAV-HP
      has been identified recently. Here an additional avian ev/J 4.1 endogenous
      sequence, ev/J 4.1 Rb, is reported. ev/J 4.1 Rb has the most extensive amino acid
      identity ever described for an endogenous envelope protein with the ALV-J avian
      leukosis virus. Here, we also demonstrate that ev/J 4.1 Rb functionally
      pseudotypes murine leukaemia virions and leads to a complete reciprocal
      interference with ALV-J envelopes. This is the first demonstration of such a high
      level of envelope interference between endogenous and exogenous avian
      retroviruses. Our results provide additional clues on the co-evolution of
      retroviral sequences among vertebrates.

PMID- 14645906
TI  - Structural disorder and modular organization in Paramyxovirinae N and P.
AB  - The existence and extent of disorder within the replicative complex (N, P and the
      polymerase, L) of Paramyxovirinae were investigated, drawing on the discovery
      that the N-terminal moiety of the phosphoprotein (P) and the C-terminal moiety of
      the nucleoprotein (N) of measles virus are intrinsically unstructured. We show
      that intrinsic disorder is a widespread property within Paramyxovirinae N and P,
      using a combination of different computational approaches relying on different
      physico-chemical concepts. Notably, experimental support that has often gone
      unnoticed for most of the predictions has been found in the literature.
      Identification of disordered regions allows the unveiling of a common
      organization in all Paramyxovirinae P, which are composed of six modules defined
      on the basis of structure or sequence conservation. The possible functional
      significance of intrinsic disorder is discussed in the light of experimental
      data, which show that unstructured regions of P and N are involved in numerous
      interactions with several protein and protein-RNA partners. This study provides a
      contribution to the rather poorly investigated field of intrinsically disordered
      proteins and helps in targeting protein domains for structural studies.

PMID- 14645907
TI  - Evaluation of attenuation, immunogenicity and efficacy of a bovine parainfluenza
      virus type 3 (PIV-3) vaccine and a recombinant chimeric bovine/human PIV-3
      vaccine vector in rhesus monkeys.
AB  - Restricted replication in the respiratory tract of rhesus monkeys is an intrinsic
      property of bovine parainfluenza virus type 3 (bPIV-3) strains. This host range
      phenotype of bPIV-3 has been utilized as a marker to evaluate the attenuation of
      bPIV-3 vaccines for human use. Two safety, immunogenicity and efficacy studies in
      primates evaluated and compared three human parainfluenza virus type 3 (hPIV-3)
      vaccine candidates: biologically derived bPIV-3, a plasmid-derived bPIV-3 (r-bPIV
      3) and a chimeric bovine/human PIV-3 (b/hPIV-3). These studies also examined the
      feasibility of substituting Vero cells, cultured in the presence or absence of
      foetal bovine serum, for foetal rhesus lung-2 (FRhL-2) cells as the tissue
      culture substrate for the production of bPIV-3 vaccine. The results demonstrated
      that (i) Vero cell-produced bPIV-3 was as attenuated, immunogenic and efficacious
      as bPIV-3 vaccine grown in FRhL-2 cells, (ii) plasmid-derived bPIV-3 was as
      attenuated, immunogenic and efficacious as the biologically derived bPIV-3 and
      (iii) the b/hPIV-3 chimera displayed an intermediate attenuation phenotype and
      protected animals completely from hPIV-3 challenge. These results support the use
      of bPIV-3 vaccines propagated in Vero cells in human clinical trials and the use
      of b/hPIV-3 as a virus vaccine vector to express foreign viral antigens.

PMID- 14645908
TI  - PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA
      translation initiation complexes.
AB  - It has previously been shown that influenza virus NS1 protein enhances the
      translation of viral but not cellular mRNAs. This enhancement occurs by
      increasing the rate of translation initiation and requires the 5'UTR sequence,
      common to all viral mRNAs. In agreement with these findings, we show here that
      viral mRNAs, but not cellular mRNAs, are associated with NS1 during virus
      infection. We have previously reported that NS1 interacts with the translation
      initiation factor eIF4GI, next to its poly(A)-binding protein 1 (PABP1)
      interacting domain and that NS1 and eIF4GI are associated in influenza virus
      infected cells. Here we show that NS1, although capable of binding poly(A), does
      not compete with PABP1 for association with eIF4GI and, furthermore, that NS1 and
      PABP1 interact both in vivo and in vitro in an RNA-independent manner. The
      interaction maps between residues 365 and 535 in PABP1 and between residues 1 and
      81 in NS1. These mapping studies, together with those previously reported for NS1
      eIF4GI and PABP1-eIF4GI interactions, imply that the binding of all three
      proteins would be compatible. Collectively, these and previously published data
      suggest that NS1 interactions with eIF4GI and PABP1, as well as with viral mRNAs,
      could promote the specific recruitment of 43S complexes to the viral mRNAs.

PMID- 14645909
TI  - Chronic hepatitis delta virus infection with genotype IIb variant is correlated
      with progressive liver disease.
AB  - We determined the sequence of the hepatitis delta virus (HDV) genome in 40
      Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan.
      Consensus sequences from 33 HDV full genomes out of a total of 40 patients were
      determined by directly sequencing four partially overlapping PCR products.
      Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV
      genotype I (two patients), genotype IIa (one patient) and genotype IIb (30
      patients). Among the 30 genotype IIb patients, there were two clusters of genetic
      variants. One group consisted of six isolates showing significant homology with
      genotype IIb, previously reported from Taiwan. The other group consisted of 24
      isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb
      M). When the genetic structures were compared in detail between IIb and IIb-M,
      characteristic variations were found in the C-terminal sequence of the large
      delta antigen-conferring packaging signal as well as the RNA editing site.
      Determination of subclasses of genotype IIb in a total of 37 patients, including
      seven HDV patients whose partial HDV sequence was determined, revealed eight
      patients with IIb and 29 patients with IIb-M. Although there was no significant
      difference in the clinical background or virological state of hepatitis B virus
      between these two groups, patients with genotype IIb-M showed greater progression
      of chronic hepatitis and cirrhosis than those with genotype IIb (P=0.0009). These
      data indicate the existence of a genetic subgroup of HDV genotype IIb, which is
      associated with different clinical characteristics and which could be related to
      genetic variations in functionally important parts of the HDV genome.

PMID- 14645910
TI  - Proliferative growth of SARS coronavirus in Vero E6 cells.
AB  - An isolate of SARS coronavirus (strain 2003VA2774) was obtained from a patient
      and used to infect Vero E6 cells. The replication cycle of the virus was followed
      from 1 to 30 h post-infection (p.i.). It was surprising to observe the swift
      growth of this human virus in Vero cells. Within the first hour of infection, the
      most obvious ultrastructural change was the proliferation of the Golgi complexes
      and related vesicles accompanied by swelling of some of the trans-Golgi sacs.
      Extracellular virus particles were present by 5 h p.i. in about 5 % of the cells
      and this increased dramatically to about 30 % of the cell population within an
      hour (6 h p.i.). Swollen Golgi sacs contained virus nucleocapsids at different
      stages of maturation. These virus precursors were also in large vacuoles and in
      close association with membrane whorls. The membrane whorls could be the
      replication complexes, since they appeared rather early in the replication cycle.
      As infection progressed from 12 to 21 h p.i., the cytoplasm of the infected cells
      was filled with numerous large, smooth-membraned vacuoles containing a mixture of
      mature virus and spherical cores. Several of these vacuoles were close to the
      cell periphery, ready to export out the mature progeny virus particles via
      exocytosis. By 24 to 30 h p.i., crystalline arrays of the extracellular virus
      particles were seen commonly at the cell surface.

PMID- 14645911
TI  - The mechanism of cell death during West Nile virus infection is dependent on
      initial infectious dose.
AB  - The mechanism of West Nile (WN) virus-induced cell death is determined by the
      initial infectious dose. In Vero cells infected with WN virus at an m.o.i. of 10
      or greater, morphological changes characteristic of necrosis were observed as
      early as 8 h post-infection (p.i.). Pathological changes included extensive cell
      swelling and loss of plasma membrane integrity, as revealed by optical and
      electron microscopy. High extracellular lactate dehydrogenase (LDH) activity was
      observed together with leakage of the high mobility group 1 (HMGB1) protein into
      the extracellular space. When cells undergo necrosis, they release the HMGB1
      protein, a pro-inflammatory mediator cytokine. At high infectious doses, loss of
      cell plasma membrane integrity was due to the profuse budding of WN progeny virus
      particles during maturation. When this profuse budding process was disrupted
      using cytochalasin B, LDH activity was reduced dramatically. In contrast, WN
      virus-induced cell killing occurred predominantly by apoptosis when cells were
      infected with an m.o.i. of </=1; the process of apoptosis observed was much later
      after infection (32 h p.i.). Fragmentation of DNA, chromatin condensation and
      formation of apoptotic bodies were all observed. This WN virus-induced apoptosis
      pathway was initiated by the release of cytochrome c from the mitochondria and
      was accompanied by the formation of apoptosomes. In turn, this led to the
      activation of caspase-9 and -3, and to the cleavage of the poly(ADP-ribose)
      polymerase.

PMID- 14645912
TI  - Induction of an antigen-specific immune response and partial protection of cattle
      against challenge infection with foot-and-mouth disease virus (FMDV) after
      lipopeptide vaccination with FMDV-specific B-cell epitopes.
AB  - To evaluate the potential of chemically synthesized lipopeptides for vaccination
      against foot-and-mouth disease (FMD), seven lipopeptides containing the
      immunostimulating principle of bacterial lipoproteins and linear B-cell epitopes
      of FMDV strain O(1)Kaufbeuren (O(1)K) were used to immunize cattle (n=7). Animals
      were vaccinated once and 21 days after immunization animals were infected with
      the homologous virus. Four animals were protected. After vaccination, as well as
      after challenge infection, B- and T-cell responses were examined. Sera were
      tested for virus- and peptide-specific antibodies and showed after vaccination
      only a weak antibody response. After challenge infection, an increase in antibody
      titre was obvious but there was no correlation between antibody titre and
      protection. The reactivity of the cellular immune system was detected by analyses
      of PBMCs for virus- and peptide-specific T-lymphocytes. With regard to the virus
      specific T-lymphocytes, a heterogeneous reactivity could be shown. No correlation
      between virus-specific T-cell proliferation and protection was found. Obvious was
      the fact that all protected animals showed after vaccination a strong T-cell
      response against at least one of the peptides used for immunization. These
      results suggest a correlation between the onset of an antigen-specific T-cell
      reaction and protection.

PMID- 14645914
TI  - A novel poxvirus lethal to red squirrels (Sciurus vulgaris).
AB  - A parapoxvirus has been implicated in the decline of the red squirrel in the
      United Kingdom. Virus was isolated from an outbreak of lethal disease in red
      squirrels in the north-east of England. Experimental infection of captive-bred
      red squirrels confirmed that this virus was the cause of the severe skin lesions
      observed. Electron microscopic examination of the virus showed that it had a
      morphology typical of parapoxviruses whilst preliminary sequence data suggested a
      genomic G+C composition of approximately 66 %, again similar to that found in
      other parapoxviruses. However Southern hybridization analysis failed to detect
      three known parapoxvirus genes, two of which have been found so far only in the
      genus parapoxvirus. Comparative sequence analysis of two other genes, conserved
      across the eight recognized chordopoxvirus genera, suggests that the squirrel
      virus represents a previously unrecognized genus of the chordopoxvirus.

PMID- 14645913
TI  - Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1.
AB  - Yaba-like disease virus (YLDV) genes 7L and 145R are located on opposite ends of
      the genome and are predicted to encode 7-transmembrane proteins (7-TM) that share
      53 and 44 % amino acid identity, respectively, to human CC chemokine receptor 8
      (hCCR8). In this report, we demonstrate that early after infection with YLDV,
      cells acquire the ability to bind human CCL1. By expression of genes 7L and 145R
      in vaccinia virus, we demonstrated that each protein is glycosylated and is
      exposed on the cell surface with the N terminus outside the cell. Protein 7L, but
      not 145R, is able to bind hCCL1 (K(d)=0.6+/-0.13 nM) and couple to heterotrimeric
      G-proteins and to activate the extracellular signal-regulated kinases (ERK1/2).
      7L binds several chemokines including the viral chemokines vMIPI and vMIPII and
      hCCL7/MCP3. This binding seems species-specific as 7L does not bind the murine
      orthologues of CCL1 and CCL7 in the assays used. This represents the first
      example of a poxviral 7-TM chemokine receptor that has functional interactions
      with a human chemokine.

PMID- 14645915
TI  - Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT)
      virus leads to attenuation in chickens, and UL0 mutants expressing influenza
      virus haemagglutinin (H7) protect against ILT and fowl plague.
AB  - Infectious laryngotracheitis virus (ILTV), a member of the Alphaherpesvirinae,
      possesses several unique genes. One of them, UL0, encodes an abundantly expressed
      protein that accumulates in the nuclei of ILTV-infected cells. This study
      demonstrates that this protein is dispensable for in vitro virus replication and
      that UL0 deletion mutants exhibit only minor growth defects in cultured cells.
      The UL0 gene locus of ILTV was also used for insertion of foreign DNA sequences
      encoding enhanced GFP or haemagglutinin (HA), subtype H7, of a highly pathogenic
      avian influenza virus under the control of the human cytomegalovirus immediate
      early gene promoter. Expression of foreign proteins was shown by
      (immuno)fluorescence tests and Western blot analyses. After experimental
      infection of chickens, UL0 deletion mutants proved to be attenuated when compared
      to both parental wild-type ILTV and an UL0 rescue mutant. Nevertheless, all
      animals immunized with UL0-negative ILTV were protected from clinical disease
      after subsequent infection with virulent ILTV. Furthermore, all animals immunized
      with HA-expressing ILTV survived a lethal challenge with H7 subtype avian
      influenza virus with minimal clinical signs. Thus, an UL0-negative and HA
      expressing ILTV recombinant may be used as a bivalent live virus vaccine against
      ILT and fowl plague. Unlike inactivated influenza virus vaccines, HA-expressing
      ILTV recombinants should be suitable for mass application and would also permit
      serological discrimination between vaccinated and virus-infected animals in the
      field.

PMID- 14645916
TI  - Complex alternative processing of human cytomegalovirus UL37 pre-mRNA.
AB  - Differentially processed human cytomegalovirus (HCMV) UL37 RNAs encode
      biologically significant proteins. Due to the recent discovery of alternative
      UL37 exon 3 (UL37x3) splice donors, permissively infected cells were thoroughly
      examined for additional alternatively spliced UL37 RNAs. Newly described donors
      within UL37 exon 1 (nt 52520) and intron 1 (nt 52209) as well as UL37x3 di (nt
      50770) and dii (nt 50782) were differentially spliced to known downstream UL37
      acceptors. The alternatively spliced UL37(S), UL37(L), UL37(di) and UL37d(ii)
      RNAs predictably encode proteins of 83, 163, 217 and 213 residues, respectively,
      which share UL37x1 N-terminal sequences but differ downstream in their C termini.
      Moreover, temporal expression of the alternatively spliced UL37 RNAs differs
      during HCMV infection. The complexity of UL37 pre-mRNA processing is evidenced by
      the detection of 11 UL37 spliced and unspliced UL37x1 RNAs in HCMV-infected
      cells. Based upon these data, a revised HCMV UL37 gene map is presented, which
      incorporates all RNA species detected during permissive infection.

PMID- 14645917
TI  - The human cytomegalovirus UL45 gene product is a late, virion-associated protein
      and influences virus growth at low multiplicities of infection.
AB  - Human cytomegalovirus (HCMV) encodes a protein related to the large (R1) subunit
      of ribonucleotide reductase (RR), but does not encode the corresponding small
      (R2) subunit. The R1 homologue, UL45, lacks many catalytic residues, and its
      impact on deoxyribonucleotide (dNTP) production remains unknown. Here, UL45 is
      shown to accumulate at late stages of infection and to be a virion tegument
      protein. To study UL45 function in its genome context, UL45 was disrupted by
      transposon insertion. The UL45-knockout (UL45-KO) mutant exhibited a growth
      defect in fibroblasts at a low m.o.i. and also a cell-to-cell spread defect. This
      did not result from a reduced dNTP supply because dNTP pools were unchanged in
      resting cells infected with the mutant virus. Irrespective of UL45 expression,
      all cellular RR subunits - S-phase RR subunits, and the p53-dependent p53R2 -
      were induced by infection. p53R2 was targeted to the infected cell nucleus,
      suggesting that HCMV diverts a mechanism normally activated by DNA damage
      response. Cells infected with the UL45-KO mutant were moderately sensitized to
      Fas-induced apoptosis relative to those infected with the parental virus.
      Together with the report on the UL45-KO endotheliotropic HCMV mutant (Hahn et
      al., J Virol 76, 9551-9555, 2002), these data suggest that UL45 does not share
      the prominent antiapototic role attributed to the mouse cytomegalovirus homologue
      M45 (Brune et al., Science 291, 303-305, 2001).

PMID- 14645918
TI  - Antibody responses to rhesus cytomegalovirus glycoprotein B in naturally infected
      rhesus macaques.
AB  - Rhesus cytomegalovirus (RhCMV) exhibits strong parallels with human CMV (HCMV) in
      terms of nucleic and amino acid identities, natural history, and mechanisms of
      persistence and pathogenesis in its natural host, rhesus macaques (Macaca
      mulatta). To determine whether this non-human primate model would be useful to
      assess vaccine strategies for HCMV, host immune responses to RhCMV glycoprotein B
      (gB) were evaluated in RhCMV-infected monkeys. Total protein extracts were
      prepared from cells transiently transfected with an expression plasmid for either
      the full-length gB or a derivative (gBDelta, 1-680 aa) lacking both the
      transmembrane domain and cytoplasmic tail. Western blot analysis showed identical
      reactivity of macaque sera with full-length gB and its derivative gBDelta,
      indicating that the immunodominant epitopes of gB are contained in the
      extracellular portion of the protein. Using gBDelta extract as a solid phase, a
      sensitive and specific ELISA was established to characterize gB antibody
      responses in monkeys acutely and chronically infected with RhCMV. During primary
      infection (seroconversion), gB-specific antibodies developed concurrently and in
      parallel with total RhCMV-specific antibodies. However, during chronic infection
      gB-specific antibody responses were variable. A strong correlation was observed
      between neutralizing and gB-specific antibody levels in RhCMV-seropositive
      monkeys. Taken together, the results of this study indicate that, similar to host
      humoral responses to HCMV gB, anti-gB antibodies are an integral part of humoral
      immunity to RhCMV infection and probably play an important protective role in
      limiting the extent of RhCMV infection. Thus, the rhesus macaque model of HCMV
      infection is relevant for testing gB-based immune therapies.

PMID- 14645919
TI  - Identification of protein kinases responsible for phosphorylation of Epstein-Barr
      virus nuclear antigen leader protein at serine-35, which regulates its
      coactivator function.
AB  - Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a
      phosphoprotein suggested to play important roles in EBV-induced immortalization.
      Earlier studies have shown that the major site of phosphorylation of EBNA-LP by
      cellular kinase(s) is a serine residue at position 35 (Ser-35) and that the
      phosphorylation of Ser-35 is critical for regulation of the coactivator function
      of EBNA-LP (Yokoyama et al., J Virol 75, 5119-5128, 2001). In the present study,
      we have attempted to identify protein kinase(s) responsible for the
      phosphorylation of EBNA-LP at Ser-35. A purified chimeric protein consisting of
      glutathione S-transferase (GST) fused to a domain of EBNA-LP containing Ser-35
      was found to be specifically phosphorylated by purified cdc2 in vitro, while GST
      fused to a mutated domain of EBNA-LP in which Ser-35 was replaced with alanine
      was not. In addition, overexpression of cdc2 in mammalian cells caused a
      significant increase in the phosphorylation of EBNA-LP, while this increased
      phosphorylation was eliminated if Ser-35 of EBNA-LP was replaced with alanine.
      These results indicate that the cellular protein kinase cdc2 mediates the
      phosphorylation of EBNA-LP at Ser-35. Recently, we reported that cdc2 and
      conserved protein kinases encoded by herpesviruses phosphorylate the same amino
      acid residue of target proteins (Kawaguchi et al., J Virol 77, 2359-2368, 2003).
      Consistent with this, the EBV-encoded conserved protein kinase BGLF4 specifically
      mediated the phosphorylation of EBNA-LP at Ser-35. These results indicate that
      the coactivator function of EBNA-LP can be regulated by the activity of these
      cellular and viral protein kinases.

PMID- 14645920
TI  - Generation and precise modification of a herpesvirus saimiri bacterial artificial
      chromosome demonstrates that the terminal repeats are required for both virus
      production and episomal persistence.
AB  - Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus, and shares
      considerable homology with the human gammaherpesviruses Kaposi's sarcoma
      associated herpesvirus and Epstein-Barr virus. The generation of herpesvirus
      mutants is a key facet in the study of virus biology. The use of F-factor-based
      bacterial artificial chromosomes (BACs) to clone and modify the genomes of
      herpesviruses has enhanced the variety, precision and simplicity of mutant
      production. Here we describe the cloning of the genome of HVS non-transforming
      strain A11-S4 into a BAC. The cloning of the BAC elements disrupts open reading
      frame (ORF) 15 but the HVS-BAC can still replicate at levels similar to wild-type
      virus, and can persistently infect fibroblasts. The HVS-BAC was modified by RecA
      mediated recombination initially to substitute reporter genes and also to delete
      the terminal repeats (TR). After deletion of the TR, the HVS-BAC fails to enter a
      productive virus lytic cycle, and cannot establish a persistent episomal
      infection when transfected into fibroblast cell lines. This shows that while ORF
      15 is dispensable for virus function in vitro, the TR is required for both virus
      latency and lytic virus production. In addition, the HVS-BAC promises to be a
      valuable tool that can be used for the routine and precise production and
      analysis of viral mutants to further explore gammaherpesvirus biology.

PMID- 14645921
TI  - ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance
      of latency.
AB  - In vitro studies have established that the latency-associated nuclear antigen
      encoded by human Kaposi's sarcoma-associated herpesvirus and the related ORF73
      gene product of herpesvirus saimiri interact with virus origins of replication to
      facilitate maintenance of episomal DNA. Such a function implies a critical role
      for ORF73 in the establishment and maintenance of latency in vivo. To determine
      the role of ORF73 in virus pathogenesis, the ORF73 gene product encoded by murine
      herpesvirus-68 (MHV-68) was disrupted by making an ORF73 deletion mutant,
      Delta73, and an independent ORF73 frameshift mutant, FS73. The effect of the
      mutations introduced in ORF73 on MHV-68 pathogenesis was analysed in vivo using a
      well-characterized murine model system. These studies have revealed that ORF73 is
      not required for efficient lytic replication either in vitro or in vivo. In
      contrast, a severe latency deficit is observed in splenocytes of animals infected
      with an ORF73 mutant, as assessed by infectious centre reactivation assay or by
      in situ hybridization detection of latent virus. Assessment of viral genome
      positive cells in sorted splenocyte populations confirmed the absence of ORF73
      mutant virus from splenic latency reservoirs, including germinal centre B cells.
      These data indicate a crucial role for ORF73 in the establishment of latency and
      for virus persistence in the host.

PMID- 14645922
TI  - Adenovirus vector library: an approach to the discovery of gene and protein
      function.
AB  - A method was developed to generate a complex cDNA expression library within an
      adenovirus type 5 (Ad5)-based vector backbone, termed AdLibrary. Construction of
      the AdLibrary entailed the conversion of an Ad5 genome-containing cosmid to
      infectious virus particles. The Ad5 genome was modified by replacing the E1A and
      E1B genes with a Rous sarcoma virus-driven expression cassette. Conversion was
      accomplished by liberating the viral genome by restriction enzyme digestion and
      transfection in HEK 293 cells, which support the growth of E1A/E1B-deficient
      virus. A test AdLibrary demonstrated the possibility of converting and
      identifying a marker gene present at a frequency of 1/10(5) in the cosmid
      library. To demonstrate the utility of this technology, an AdLibrary was used to
      isolate a viral gene by its biological function. Virus growth was selected for
      with an AdLibrary on A549 cells, which do not complement for E1A/E1B function.
      The AdLibrary was generated with cDNAs derived from HeLa cells productively
      infected with Ad5. A cDNA corresponding to Ad5 E1A 13S was selected and isolated
      from the AdLibrary using this strategy. Since multiple genes are assayed
      simultaneously, this technology should expedite the discovery of genes affecting
      defined biological activities. This AdLibrary approach provides an opportunity to
      exploit the efficient gene delivery capabilities of adenovirus vectors for the
      rapid discovery of gene and protein function.

PMID- 14645923
TI  - Adenovirus core protein VII contains distinct sequences that mediate targeting to
      the nucleus and nucleolus, and colocalization with human chromosomes.
AB  - During adenovirus infection, following capsid dissociation, core protein VII
      enters the host cell nucleus complexed with adenovirus DNA. In order to determine
      whether protein VII may have an active role in this nuclear import, regions of
      the preVII gene were amplified by PCR, and further oligonucleotide mutants were
      designed with site-directed mutation of codons for the basic amino acids arginine
      and lysine. Fragments were cloned into a mammalian expression plasmid to express
      the peptides as N-terminal fusions to enhanced green fluorescent protein. Results
      demonstrate that preVII protein contains both nuclear and nucleolar targeting
      sequences. Such signals may be important in the delivery of adenovirus DNA to the
      host cell nucleus during adenovirus infection. Furthermore, the data suggest that
      protein VII may bind to human chromosomes by means of two distinct domains, one
      sharing homology with the N-terminal regulatory tail of histone H3.

PMID- 14645924
TI  - A promoter within the E6 ORF of human papillomavirus type 16 contributes to the
      expression of the E7 oncoprotein from a monocistronic mRNA.
AB  - Human papillomavirus type 16 (HPV-16) has the capacity to transform human primary
      keratinocytes. Maintenance of the transformed phenotype requires constitutive
      expression of the oncoproteins E6 and E7. The low-risk HPV types express E7 from
      monocistronic mRNA, but for the high-risk types, no mRNA that encodes E7 as the
      first open reading frame (ORF) has been identified. We recently identified a
      transcription initiation site within the E6 ORF of HPV-16 at nt 542. In the
      present study we have characterized the P542 promoter, which putatively controls
      monocistronic expression of E7. The monocistronic mRNA is not very abundant, but
      we have shown that an E7-luciferase fusion protein can be expressed in SiHa cells
      from a monocistronic HPV-16 transcript initiated at nt 542. The monocistronic
      mRNA expresses E7-luciferase more efficiently than the most abundant in vivo-like
      mRNA E6*IE7, initiated by P97 and spliced from nt 226 to 409. Furthermore, the
      translation initiation of E7 is most abundant from the monocistronic mRNA. We
      have also shown that the P542 promoter is downregulated by the transcription
      factor activator protein 4 (AP-4) and the differentiation-dependent factor hSkn
      1a, both binding downstream of the transcription initiation site. In conclusion,
      we have found that P542 is a relatively weak promoter compared with P97 and may
      be downregulated in differentiated epithelial cells.

PMID- 14645925
TI  - Murine pneumotropic virus VP1 virus-like particles (VLPs) bind to several cell
      types independent of sialic acid residues and do not serologically cross react
      with murine polyomavirus VP1 VLPs.
AB  - The ability of murine pneumotropic virus (MPtV) major capsid protein VP1 to form
      virus-like particles (VLPs) was examined. MPtV-VLPs obtained were used to
      estimate the potential of MPtV to attach to different cells and to assess some
      characteristics of the MPtV cell receptor. Furthermore, to evaluate if MPtV-VLPs
      could potentially complement murine polyomavirus (MPyV) VP1 VLPs (MPyV-VLPs) as
      vectors for prime-boost gene therapy, the capability of MPtV-VLPs to
      serologically cross react with MPyV-VLPs and to transduce DNA into cells was
      examined. MPtV VP1 obtained in a recombinant baculovirus system formed MPtV-VLPs
      readily. MPtV-VLPs were shown by FACS analysis to bind to different cells,
      independent of MHC class I antigen expression. In addition, MPtV-VLPs did not
      cause haemagglutination of red blood cells and MPtV-VLP binding to cells was
      neuraminidase resistant but mostly trypsin and papain sensitive, indicating that
      the MPtV receptor lacks sialic acid components. When tested by ELISA and in vivo
      neutralization assays, MPtV-VLPs did not serologically cross react with MPyV
      VLPs, suggesting that MPtV-VLPs and MPyV-VLPs could potentially be interchanged
      as carriers of DNA in repeated gene therapy. Finally, MPtV-VLPs were shown to
      transduce foreign DNA in vitro and in vivo. In conclusion, the data suggest that
      MPtV-VLPs, and possibly also MPtV, bind to several different cell types, that
      binding is neuraminidase resistant and that MPtV-VLPs should potentially be able
      to complement MPyV-VLPs for prime-boost gene transfer in vivo.

PMID- 14645926
TI  - Cytokine profiles of peripheral blood mononuclear cells from pigs with
      postweaning multisystemic wasting syndrome in response to mitogen, superantigen
      or recall viral antigens.
AB  - In vitro cytokine profiles of peripheral blood mononuclear cells (PBMC) from pigs
      with postweaning multisystemic wasting syndrome (PMWS) and healthy pigs were
      determined in response to recall viral antigens (porcine circovirus type 2;
      PCV2), mitogens (phytohaemagglutinin) or superantigens (staphylococcal
      enterotoxin B). PBMC from PMWS-affected pigs, in contrast to those from healthy
      pigs, responded to recall PCV2 antigen by releasing IL-10 and IFN-gamma, but they
      were less able or even unable to produce IL-4, IL-2 or IFN-gamma upon challenge
      with mitogen or superantigen. Moreover, only PCV2 had the ability to downregulate
      or suppress the release of IL-4 and IL-2 from PBMC from both healthy and diseased
      animals, and to stimulate the production of pro-inflammatory cytokines (IL-1beta,
      IL-8). In conclusion, the immune system cells of PMWS pigs have a diminished
      ability to perform their immunological functions upon viral or immunostimulatory
      molecules. In addition, PCV2 can alter the functionality of PBMC in both healthy
      and PMWS pigs.

PMID- 14645927
TI  - Characterization of Cestrum yellow leaf curling virus: a new member of the family
      Caulimoviridae.
AB  - Cestrum yellow leaf curling virus (CmYLCV) has been characterized as the
      aetiological agent of the Cestrum parqui mosaic disease. The virus genome was
      cloned and the clone was proven to be infectious to C. parqui. The presence of
      typical viroplasms in virus-infected plant tissue and the information obtained
      from the complete genomic sequence confirmed CmYLCV as a member of the
      Caulimoviridae family. All characteristic domains conserved in plant
      pararetroviruses were found in CmYLCV. Its genome is 8253 bp long and contains
      seven open reading frames (ORFs). Phylogenetic analysis of the relationships with
      other members of the Caulimoviridae revealed that CmYLCV is closely related to
      the Soybean chlorotic mottle virus (SbCMV)-like genus and particularly to SbCMV.
      However, in contrast to the other members of this genus, the primer-binding site
      is located in the intercistronic region following ORF Ib rather than within this
      ORF, and an ORF corresponding to ORF VII is missing.

PMID- 14645928
TI  - Independent expression of Rep and RepA and their roles in regulating bean yellow
      dwarf virus replication.
AB  - Bean yellow dwarf virus (BeYDV) is a mastrevirus specific for dicotyledenous
      hosts. It contains four ORFs encoding a movement protein, a coat protein, and two
      Rep gene products, Rep and RepA, which are encoded by two overlapping ORFs. In
      this study, the roles of Rep and RepA in regulating replication of the BeYDV
      based replicon were investigated by uncoupling them and placing Rep and RepA each
      under constitutive promoter control. Constitutive expression of both Rep and RepA
      supported replication and enhanced gene expression. When a reporter plasmid
      containing the Rep gene in the context of its native promoter was supplemented
      with additional Rep protein, replication was enhanced but the increase in gene
      expression was found to be more modest. Furthermore, expression of constitutively
      expressed RepA alone was found to reduce replication of this reporter construct
      as well as delay BeYDV replication in general. The effect of a RepA mutant with
      an altered retinoblastoma-related-protein binding motif on the efficiency of
      BeYDV replication was also examined. This mutant was found to severely diminish
      replication efficiency. Finally, the relationship of BeYDV coat protein to virus
      replication and reporter gene expression was investigated. Addition of coat
      protein increased accumulation of single-stranded DNA and had a detrimental
      effect on reporter gene expression.

PMID- 14645929
TI  - Posterior midgut and hindgut are both sites of acquisition of Cucurbit aphid
      borne yellows virus in Myzus persicae and Aphis gossypii.
AB  - Members of the family Luteoviridae ('luteovirids') rely strictly on aphid vectors
      for plant-to-plant transmission. This interaction operates according to a
      persistent and circulative manner, which implies that the virions are being
      endocytosed and exocytosed across two epithelial barriers (alimentary tract and
      accessory salivary glands) in the vector's body. In several luteovirid-aphid
      vector species combinations, the route of virions in the insect has been
      investigated ultrastructurally by transmission electron microscopy (TEM). Here,
      we used TEM to follow the route of Cucurbit aphid-borne yellows virus (CABYV;
      genus Polerovirus) in its two efficient vector species, Myzus persicae and Aphis
      gossypii. We demonstrated that CABYV particles are acquired from the gut lumen to
      the haemocoel through two different sites in both aphid species, i.e. the
      posterior midgut (as for Beet western yellows virus in M. persicae) and the
      hindgut (as for Barley yellow dwarf virus complex in cereal aphids). This 'dual'
      tissue specificity of CABYV represents an original situation among viruses in the
      family Luteoviridae examined so far by TEM. A variety of virion-containing
      structures (e.g. clathrin-coated and tubular vesicles, endosome-like bodies) are
      found in intestinal cells of both types in both aphids. Release of virus
      particles from midgut and hindgut cells into the haemolymph was confirmed by
      immunotrapping using CABYV-specific antibodies. In accessory salivary glands,
      transport of CABYV virions across the cells was similar in each aphid species,
      and occurred by a transcytosis mechanism involving formation of tubular and
      coated vesicles before release of free virions in the salivary canal.

PMID- 14645930
TI  - Identification of distinct steps during tubule formation by the movement protein
      of Cowpea mosaic virus.
AB  - The movement protein (MP) of Cowpea mosaic virus (CPMV) forms tubules through
      plasmodesmata in infected plants thus enabling virus particles to move from cell
      to cell. Localization studies of mutant MPs fused to GFP in protoplasts and
      plants identified several functional domains within the MP that are involved in
      distinct steps during tubule formation. Coinoculation experiments and the
      observation that one of the C-terminal deletion mutants accumulated uniformly in
      the plasma membrane suggest that dimeric or multimeric MP is first targeted to
      the plasma membrane. At the plasma membrane the MP quickly accumulates in
      peripheral punctuate spots, from which tubule formation is initiated. One of the
      mutant MPs formed tubules containing virus particles on protoplasts, but could
      not support cell-to-cell movement in plants. The observations that this mutant MP
      accumulated to a higher level in the cell than wt MP and did not accumulate in
      the cell wall opposite infected cells suggest that breakdown or disassembly of
      tubules in neighbouring, uninfected cells is required for cell-to-cell movement.

PMID- 14645931
TI  - Transfection of prion protein gene suppresses coxsackievirus B3 replication in
      prion protein gene-deficient cells.
AB  - The susceptibility of prion protein gene (Prnp)-null cells to coxsackievirus B3
      (CVB3) was investigated. Primary cultures of murine Prnp(-/-) brain cells were
      more sensitive to CVBs than corresponding cells from wild-type mice. The viral
      susceptibility of a Prnp-null cell line (HpL3-4) derived from the murine
      hippocampus was compared with that of two established cell lines (HeLa and HEp-2)
      that are widely employed for CVB3 studies. After infection with CVB3, HpL3-4
      cells showed a very rapid and complete cytopathic effect (CPE). CPE developed
      earlier and viruses replicated at higher titres in HpL3-4 cells compared with
      HeLa and HEp-2 cells. Under a semi-solid medium, plaques developed rapidly in
      CVB3-infected HpL3-4 cells. To confirm the effect of Prnp on virus infection, a
      Prnp(-/-) cell line and a Prnp-transfected neuronal cell line were analysed. The
      replication and release of infectious particles of CVB3 in Prnp(-/-) cells were
      significantly more effective than those of the Prnp-transfected cell line. Levels
      of type I interferon (IFN) after CVB3 infection were higher in the Prnp
      transfected cell line than in Prnp(-/-) cells, whereas apoptotic cells were more
      obvious in the Prnp(-/-) cells than in those of the Prnp-transfected cell line.
      These findings suggest that the absence of Prnp retards the induction of CVB3
      induced IFNs, resulting in an enhanced CVB3 production and apoptotic cell death.
      Furthermore, our data indicate that the HpL3-4 cell line may provide a novel and
      sensitive system for isolation of CVB3 from clinical specimens.

PMID- 14645932
TI  - Epidemiological implications of the susceptibility to BSE of putatively resistant
      sheep.
AB  - The experimental infection of sheep with bovine spongiform encephalopathy (BSE)
      by the oral route and the likelihood that sheep were fed BSE-infected meat and
      bone meal has led to extensive speculation as to whether or not sheep are
      naturally infected with BSE. In response, the UK government has initiated the
      National Scrapie Plan (NSP), an ambitious pound 120 million per year project to
      create a BSE- and scrapie-resistant national sheep flock, by selectively breeding
      for a genotype of sheep believed to be resistant to both diseases. This genotype
      has recently been shown to be susceptible to BSE by intracerebral (i.c.)
      inoculation. Should these sheep be sufficiently susceptible to BSE via natural
      transmission, the NSP might fail. Here we estimate the susceptibility of this
      genotype to horizontal (sheep-to-sheep) transmission of BSE by comparison with
      more extensive oral and i.c. exposure data for other sheep genotypes. We show
      that a previous estimate of the risk of BSE transmission to sheep via the
      feedborne route remains robust. However, using a mathematical model for the
      within-flock transmission of BSE, we show that, while the best estimate indicates
      that the NSP should be successful, current data cannot exclude the failure of the
      NSP.

PMID- 14645933
TI  - Youth tobacco use research in the USA: progress and challenges.

PMID- 14645934
TI  - Effects of motivational interviewing on smoking cessation in adolescents with
      psychiatric disorders.
AB  - OBJECTIVE: To test the hypothesis that among adolescent smokers hospitalised for
      psychiatric and substance use disorders, motivational interviewing (MI) would
      lead to more and longer quit attempts, reduced smoking, and more abstinence from
      smoking over a 12 month follow up. DESIGN: Randomised control trial of MI versus
      brief advice (BA) for smoking cessation, with pre- and post-intervention
      assessment of self efficacy and intentions to change, and smoking outcome
      variables assessed at one, three, six, nine, and 12 month follow ups. SETTING: A
      private, university affiliated psychiatric hospital in Providence, Rhode Island,
      USA. PATIENTS OR OTHER PARTICIPANTS: Consecutive sample (n = 191) of 13-17 year
      olds, admitted for psychiatric hospitalisation, who smoked at least one cigarette
      per week for the past four weeks, had access to a telephone, and did not meet DSM
      IV criteria for current psychotic disorder. INTERVENTIONS: MI versus BA. MI
      consisted of two, 45 minute individual sessions, while BA consisted of 5-10
      minutes of advice and information on how to quit smoking. Eligible participants
      in both conditions were offered an eight week regimen of transdermal nicotine
      patch upon hospital discharge. MAIN OUTCOME MEASURES: Point prevalence
      abstinence, quit attempts, changes in smoking rate and longest quit attempt.
      Proximal outcomes included intent to change smoking behaviour (upon hospital
      discharge), and self efficacy for smoking cessation. RESULTS: MI did not lead to
      better smoking outcomes compared to BA. MI was more effective than BA for
      increasing self efficacy regarding ability to quit smoking. A significant
      interaction of treatment with baseline intention to quit smoking was also found.
      MI was more effective than BA for adolescents with little or no intention to
      change their smoking, but was actually less effective for adolescents with pre
      existing intention to cut down or quit smoking. However, the effects on these
      variables were relatively modest and only moderately related to outcome.
      Adolescents with comorbid substance use disorders smoked more during follow up
      while those with anxiety disorders smoked less and were more likely to be
      abstinent. CONCLUSIONS: The positive effect of MI on self efficacy for quitting
      and the increase in intention to change in those with initially low levels of
      intentions suggest the benefits of such an intervention. However, the effects on
      these variables were relatively modest and only moderately related to outcome.
      The lack of overall effect of MI on smoking cessation outcomes suggests the need
      to further enhance and intensify this type of treatment approach for adolescent
      smokers with psychiatric comorbidity.

PMID- 14645935
TI  - A randomised clinical trial of nicotine patches for treatment of spit tobacco
      addiction among adolescents.
AB  - BACKGROUND: This study tested the efficacy of nicotine patches in combination
      with behavioural therapy for the treatment of adolescent spit tobacco addiction.
      Prior interventions had resulted in mean cessation rates below 15% at one year.
      METHODS: This study, the PATCH Project, used a three group, placebo controlled,
      randomised clinical trial design. The control group received a standard 3-5
      minute counselling followed by a two week follow up phone call. The two
      intervention groups received a six week behavioural intervention; in addition,
      one group received active nicotine patches while the other group received placebo
      patches. Both groups received quarterly stage based telephone counselling.
      RESULTS: At one year, the usual care group's spit tobacco cessation rate was
      11.4% (exact 95% confidence interval (CI) 6.1% to 19.1%), placebo patch 25.0%
      (95% CI 16.9% to 34.7%), and the active patch 17.3% (95% CI 10.4% to 26.3%). When
      both patch groups were combined, the cessation rate was 21.2% (95% CI 15.7% to
      27.6%). The cessation rates for active and placebo patch were not significantly
      different (exact two sided p = 0.22), while the combined patch groups had a
      significantly greater cessation rate than usual care (exact two sided p = 0.04).
      CONCLUSIONS: The behavioural intervention proved to be about twice as successful
      as previous interventions, but the nicotine patch offered no improvement in
      cessation rates. The behavioural intervention is based on publicly available
      materials and can be easily adapted for widespread use, particularly in high
      schools.

PMID- 14645936
TI  - Understanding factors that influence smoking uptake.
AB  - OBJECTIVE: To explore relationships between patterns of smoking uptake and social
      context and attitudinal variables. DESIGN: Cross sectional survey. SETTING:
      Public schools in Tucson, Arizona and Albuquerque, New Mexico. PARTICIPANTS: 982
      children in grades 6-9 (ages 11-15 years). MAIN OUTCOME MEASURES: Items measuring
      smoking history, nicotine dependence and quit attempts, susceptibility to smoking
      in the future, smoking norms, use of other tobacco products, attitudes toward
      smoking, and demographic characteristics. RESULTS: Overall, 43% of children had
      smoked a cigarette and 57% had never used them. Ever smokers lived in social
      contexts with more smoking and where smoking was normative. Among never users,
      25% are susceptible to smoking; these children have positive attitudes toward
      smoking, do not feel social pressure to stay off cigarettes, and had more friends
      who smoked. Among ever users, 36% were currently smoking in the past 30 days.
      Current users also lived in social context with more smoking and had positive
      attitudes toward smoking. Most users had tried to stop smoking. Only 9% of
      current users smoked daily; 29% had not smoked a whole cigarette. Greater
      cigarette consumption was associated with more favourable attitudes toward
      smoking. Most of past users were in early uptake: 95% had smoked less than 100
      cigarettes but 49% were susceptible to smoking again. CONCLUSIONS: There is
      promise in differentiating subgroups among the never, past and current use of
      cigarettes. Susceptibility within each of these groups was associated with
      similar patterns of attitudes and social context. These patterns in smoking
      uptake need to be confirmed prospectively.

PMID- 14645937
TI  - "Start to stop": results of a randomised controlled trial of a smoking cessation
      programme for teens.
AB  - OBJECTIVE: To examine the feasibility, acceptability, and effectiveness of a
      school based smoking cessation programme among students caught smoking at school.
      DESIGN: A randomised controlled trial comparing cessation rates among students in
      a behavioural cessation programme and those receiving self help materials only.
      SETTING: Eighteen schools in the Memphis, Tennessee area. SUBJECTS: Two hundred
      and sixty one adolescent cigarette smokers (166 male, 95 female) averaging 15.8
      years of age. INTERVENTION: Students assigned to the intervention received a four
      session behavioural treatment programme administered individually by a health
      educator. In addition, these students received stage matched intervention in
      brief phone calls monthly until the one year follow up. MAIN OUTCOME MEASURE:
      Self reported and biochemically verified smoking cessation at post-test and 12
      month follow up. RESULTS: Recruiting students who were caught smoking at school
      proved to be highly successful. Participants rated the programme favourably, and
      retention rates were high. Although treated participants improved more in tobacco
      related knowledge relative to controls (p = 0.002), there were no group
      differences in changes in attitudes toward smoking. In addition, treated and
      control participants demonstrated no significant differences in cessation rates
      both at post-test and follow up. Comparisons between self reported cessation
      rates and those obtained under bogus pipeline conditions or with biochemical
      verification suggested significant falsification of cessation among participants.
      CONCLUSIONS: Our results failed to demonstrate any significant effect of the
      cessation programme on smoking rates for treated adolescents compared with
      controls. Our findings also highlight the importance of utilising strong
      methodology in research on adolescent smoking cessation, including control groups
      and biochemical verification of smoking status.

PMID- 14645938
TI  - The feasibility of evaluating a tobacco control intervention for working youth.
AB  - OBJECTIVES: To describe the feasibility of implementing evaluation methods for a
      worksite tobacco control intervention for teens. Indicators of feasibility
      included employment stability, response rates to multiple surveys, and self
      reported 30 day smoking. DESIGN: Grocery stores that were part of a single chain
      were randomised to four intervention stores and five control stores as part of
      the SMART project, a phase II methods development study designed to reduce
      smoking among working adolescents. SUBJECTS: Data on smoking in the last 30 days
      and employment patterns were collected from working teens aged 15-18 years at
      seven data points over the 12 month intervention period using cross sectional
      surveys. RESULTS: Data on employment stability indicate that employee turnover
      rates averaged 21% over the seven administrations. Response rates for the seven
      surveys ranged from 43-77% and were slightly greater in the control stores than
      the interventions stores (71% v 59%, p = 0.06). Mean current smoking at the
      individual store level ranged from 9-32% and there was a negative correlation
      between smoking prevalence and response rate by survey and by store (-0.029, p =
      0.03). Among smokers who completed at least two surveys, there were no
      significant differences between intervention and control store on changes in the
      frequency of smoking. CONCLUSIONS: Evaluating a tobacco control intervention in
      the grocery store setting requires multiple survey assessments to monitor changes
      in smoking among adolescents. Strategies are needed to maintain high response
      rates and increase the number of multiple responses from eligible teens.

PMID- 14645939
TI  - Feasibility of implementing intervention methods in an adolescent worksite
      tobacco control study.
AB  - OBJECTIVE: To present feasibility data on SMART, the first teen worksite
      behavioural tobacco control intervention. DESIGN: This phase II study was
      designed to estimate the efficacy and feasibility of a small scale, randomised,
      controlled intervention. SETTING AND SUBJECTS: This study, addressing youths aged
      15-18 years, was implemented in four intervention and five control grocery stores
      that had an average of 44 eligible teens. INTERVENTIONS: The tobacco use
      cessation and prevention interventions were based on social influences and peer
      leader models. Employee break rooms served as centres both for interactive
      activities including open houses, teen advisory boards, peer leader interviews,
      games and contests; and non-interactive interventions including bulletin boards
      and table tents with health messages and home mailings. MAIN PROCESS MEASURES:
      Project staff collected process data on the extent of implementation of
      intervention activities, participation rates in activities, and contacts with
      peer leaders. On the final survey, teens reported on awareness of, participation
      in, and motivation for participating in project activities. RESULTS: Indicators
      of feasibility were identified and discussed, including the number of activities
      implemented, teen participation, management support, cost, and barriers to and
      facilitators of implementation. During the 12 month intervention, a mean of 24.1
      interactive activities and 55.3 non-interactive activities were implemented, and
      a mean 14.2% participation rate per activity per site was achieved. Eighty four
      per cent of teens reported being aware of SMART, and 39% reported participating
      in interactive and 67% in non-interactive activities. CONCLUSIONS: Teen smoking
      cessation rates in worksite programmes might be improved if they are conducted in
      companies where there is job stability and if teen programmes are part of
      worksite-wide tobacco control programmes that include both teens and adults.

PMID- 14645941
TI  - "Australia is one of the darkest markets in the world": the global importance of
      Australian tobacco control.
AB  - "Australia is one of the darkest markets in the world... it probably is the
      darkest, I mean ourselves and Canada fight every month for who's got the darkest
      conditions to do tobacco manufacturing and marketing. And one of the things we
      can offer the world is what we do best, which is how to work, maximize,
      proactively drive our market position in a market that's completely dark. Now
      that takes a different skillset... a different type of learning. We need to
      export that... we know we have a lot of expatriates who come down to Australia
      for learning. they can come here and learn these techniques and take them back to
      Europe or Latin America or to the United States or to Africa... But the other
      thing that is really good for us is that we are also a huge net exporter of
      Australian talent. about 30 or 40 people currently off-shore... We do things
      really differently here than most other BAT organizations." David Crowe,
      Marketing Director, British American Tobacco (BAT) Australia(1).

PMID- 14645940
TI  - Adolescent and young adult tobacco prevention and cessation: current status and
      future directions.
AB  - OBJECTIVE: To summarise the evidence on adolescent and young adult prevention and
      cessation, and provide future directions for research. DATA SOURCES: Data were
      collected from published literature. Searches for adolescent prevention were
      conducted using PubMed, PsycInfo, and ERIC; and for cessation, PubMed, and two
      major reviews that span January 1978 to May 2002. PubMed, PsychInfo, and SCCI
      were searched for young adults from January 1990 to May 2002. STUDY SELECTION:
      Data included smoking prevention studies published from January 1990 to May 2002
      and conducted in the USA; all identified smoking cessation studies for
      adolescents. Young adult data were limited to initiation and cessation studies.
      DATA EXTRACTION: Extraction of data was by consensus of the authors. DATA
      SYNTHESIS: Results of the review are qualitative in nature using a consensus
      approach of the authors. CONCLUSIONS: School based curricula alone have been
      generally ineffective in the long term in preventing adolescents from initiating
      tobacco use but are effective when combined with other approaches such as media
      and smoke-free policies. Prevention research should consider multiple approaches
      and the social conditions that influence the development of youth problem
      behaviours including tobacco use. Because youth smoking cessation has been
      understudied to date, scientifically rigorous adolescent smoking cessation
      studies need to be conducted with attention to high risk smokers and less than
      daily smokers. Tobacco prevention and cessation for young adults needs focused
      attention. Prevention and cessation programmes need to address other tobacco
      products in addition to cigarettes.

PMID- 14645942
TI  - "It is possible he is a kind of nut": how the tobacco industry quietly promoted
      Dr William Whitby.
AB  - Dr William Whitby was a general practitioner in Sydney who, from 1978 until about
      1987, self published two books extolling the virtues of smoking and ridiculing
      anti-smoking claims. Privately the tobacco industry regarded him as "nutty",
      while nonetheless believing that his views should be promoted. They quietly
      supported him by distributing his book, offering legal advice, and persuading him
      to take media training. Many Australians would have been exposed to his views.

PMID- 14645943
TI  - "Some convincing arguments to pass back to nervous customers": the role of the
      tobacco retailer in the Australian tobacco industry's smoker reassurance campaign
      1950-1978.
AB  - BACKGROUND: Epidemiological studies and reports on smoking and health published
      in the 1950s and 1960s threatened the tobacco industry worldwide, which acted to
      reassure smokers and counteract mounting evidence that smoking posed a serious
      risk to smokers' health. OBJECTIVE: To document the use of tobacco retailers (1)
      as a conduit to pass messages of reassurance onto smokers, and (2) to recruit
      youth and women into smoking. METHODS: Review of an extensive collection of
      Australian tobacco retail trade journals (1950-1978) for articles consistent with
      the industry's efforts to counter messages about smoking and health, and how to
      attract non-smokers, particularly youth and women. RESULTS: The main arguments
      advanced in the journals included the notion that air pollution and other
      substances cause cancer, that "statistics" did not constitute proof in the
      tobacco health scare, and that the industry was committed to research into the
      causes of cancer and into developing a "safer" cigarette. CONCLUSIONS: Numerous
      articles designed to be reiterated to customers were published, arguing against
      the link between tobacco and ill health. Tobacco retailers, salesmen and retail
      trade organisations played a significant role in dissembling the tobacco health
      nexus. Tobacco retail journals may be an important component in tobacco industry
      misinformation strategies.

PMID- 14645944
TI  - "Avoid health warnings on all tobacco products for just as long as we can": a
      history of Australian tobacco industry efforts to avoid, delay and dilute health
      warnings on cigarettes.
AB  - OBJECTIVE: To review critically the history of Australian tobacco industry
      efforts to avoid, delay, and dilute pack warnings on cigarettes. DESIGN:
      Systematic keyword and opportunistic website searches of tobacco industry
      internal documents made available through the Master Settlement Agreement.
      RESULTS: Four industry strategies and six recurrent arguments used by the
      industry are described, which were used to thwart the passage of three
      generations of health warnings (implemented in 1973, 1987, and 1995). These
      strategies are shown to have been associated with major delays in the
      implementation of the warnings and in keeping them inconspicuous, unattributed to
      the industry and non-specific, and particularly in delaying the use of warnings
      about addiction. The industry today continues to oppose warnings, which might
      "repel" smokers from tobacco use. CONCLUSIONS: Efforts by governments to
      introduce potent health warnings will be resisted by the tobacco industry.
      Tobacco control advocates should anticipate and counter the strategies and
      arguments used by the industry, which are described in this paper if they wish to
      maximise the use of the pack as a vehicle for raising awareness about the harms
      of smoking.

PMID- 14645945
TI  - Smoking, disease, and obdurate denial: the Australian tobacco industry in the
      1980s.
AB  - OBJECTIVE: To contrast the Australian tobacco industry's awareness of the
      diseases caused by smoking with their aggressive public denial on the relation
      between smoking and disease in the 1980s. DESIGN: Analysis of 325 industry
      documents from the world wide web. RESULTS: In the 1980s Australian cigarette
      manufacturers were informed constantly by the international industry of the
      medical consensus that smoking caused disease. In addition Philip Morris
      (Australia) Limited received reports of Philip Morris' international biological
      research programme and visited its Richmond research facility; and WD&HO Wills
      part funded, co-managed, and contributed research to the British American Tobacco
      groups' biological research programme. Despite this knowledge, the Australian
      manufacturers had a policy of arguing to their employees, decision makers, and
      the general public that questions of smoking and disease were unresolved. The
      industry catalogued the literature, developed arguments against the main claims
      made by health groups, and attacked public health advocates who made statements
      linking smoking to death and disease. Industry studies suggested that a 20-30%
      minority of the Australian public agreed with the industry on smoking and
      disease, diminishing across the decade. CONCLUSION: Australian manufacturers were
      clearly negligent in the 1980s, deliberately working to undermine Australians'
      understandings of the diseases caused by smoking despite their own private
      knowledge. Continuing scepticism about smoking and disease, corresponding with
      the industry's deceptions, exists in Australian smokers today, suggesting that
      their actions may have slowed the rate of decline in smoking prevalence. These
      revelations provide important evidence for Australian litigation and advocacy.

PMID- 14645946
TI  - "We are anxious to remain anonymous": the use of third party scientific and
      medical consultants by the Australian tobacco industry, 1969 to 1979.
AB  - OBJECTIVE: To document the history of visits to Australia by tobacco industry
      sponsored scientists and news media reports about smoking and health matters
      generated by their visits. DESIGN: Systematic keyword and opportunistic website
      searches of tobacco industry internal documents made available through the Master
      Settlement Agreement. RESULTS: At least nine sponsored scientists visited
      Australia from 1969 until 1979. The industry sought to promote the scientists as
      independent from the industry and on occasion, scientists publicly lied about
      their industry connections. The industry was sometimes delighted with the
      extensive and favourable media coverage given to the visits. CONCLUSIONS: These
      media reports are likely to have influenced many who were exposed to them to
      believe that the evidence against smoking remained equivocal.

PMID- 14645947
TI  - "A deep fragrance of academia": the Australian Tobacco Research Foundation.
AB  - OBJECTIVES: (1) To review the history of the tobacco industry supported
      Australian Tobacco Research Foundation (ATRF)(1970-1994) for evidence of the
      industry's use of the Foundation to further its objectives that "more research
      was needed" on smoking and health and to promulgate the view that nicotine was
      not addictive. (2) To review efforts by public health advocates to discredit the
      ATRF as a public relations tool used by the Australian industry. METHODS:
      Systematic search of previously internal industry documents released through the
      US Master Settlement Agreement. RESULTS: The ATRF was headed by prestigious
      Australian medical scientists, with at least one considered by the industry to be
      "industry positive". An international ATRF symposium on nicotine was vetted by
      the industry and heavily attended by industry approved scientists. Following
      sustained criticism from the health and medical community about the industry's
      creation of the ATRF to further its objectives, the ATRF's scientific committee
      was provoked to publicly declare in 1988 that smoking was a causative agent in
      disease. This criticism led to growing ATRF boycotts by scientists and
      substandard applications, causing the industry to see the ATRF as being poor
      value-for-money and eventually abandoning it. CONCLUSIONS: The raison d'etre for
      the ATRF's establishment was to allow the Australian industry to point to its
      continuing commitment to independent medical research, with the implied corollary
      that tobacco control measures were premature in the face of insufficient evidence
      about tobacco's harms. Sustained criticism of tobacco industry funded research
      schemes can undermine their credibility among the scientific community.

PMID- 14645949
TI  - Cooperation and control: the Tobacco Institute of Australia.
AB  - OBJECTIVE: To describe the history of the Tobacco Institute of Australia (TIA),
      particularly regarding connections between local and international cigarette
      manufacturers and tobacco organisations. DESIGN: Analysis of 4541 industry
      documents from the world wide web. RESULTS: From 1978 to 1983 the TIA built
      strong international networks via ICOSI/INFOTAB and the US Tobacco Institute, and
      defended existing industry freedoms. 1983 to 1989 was the TIA's aggressive
      heyday, led primarily by John Dollisson. From 1989 to 1994, following the
      decision in Australian Federation of Consumer Organisations vs TIA, local and
      international industry lawyers assumed control. Between 1994 and 1997 a brief
      revival led into decline and then dissolution, as previously common ground became
      commercially competitive issues for the manufacturers. The TIA facilitated
      interconnectedness: between local manufacturers; via individuals who played
      multiple roles; to international tobacco organisations; through the industry's
      local and international counsel; and by acting as a conduit for information.
      CONCLUSION: The local tobacco industry was comprehensively informed on issues
      including smoking and health, and connected to the international industry, via
      the TIA. The manufacturers were closely involved in the TIA's activities, and
      cooperated through the TIA in a manner detrimental to Australian consumers. The
      TIA's conduct was the responsibility of local and international manufacturers and
      their counsel.

PMID- 14645948
TI  - "Keep a low profile": pesticide residue, additives, and freon use in Australian
      tobacco manufacturing.
AB  - OBJECTIVES: To review the Australian tobacco industry's knowledge of pesticide
      residue on Australian tobacco and its policies and practices on resisting calls
      by tobacco control advocates that consumers should be informed about pesticide
      residue as well as additives. METHODS: Review of previously internal industry
      documents relevant to pesticides and additives in Australian tobacco located from
      the Master Settlement Agreement websites. RESULTS: Between 1972 and 1994 Philip
      Morris Australia was aware that its leaf samples were often contaminated with
      pesticide residue, sometimes including organochlorine levels described by PM's
      European laboratories as being "extremely high". Consumers were not advised of
      the contamination nor products withdrawn. From 1981, the industry also resisted
      calls to declare fully the extent of use and long term safety data on all
      additives used in their products. They developed standard public responses that
      were evasive and misleading and, in 2000, implemented voluntary additive
      disclosure which allowed the companies to continue to avoid disclosure of any
      ingredient they deemed to be a trade secret. There was extensive use of ozone
      depleting freon in Australian tobacco manufacturing. Again, the industry kept
      this information away from consumers. CONCLUSIONS: Australian smokers are unable
      to make informed decisions about smoking because pesticide and additive
      disclosure remains voluntary. The Australian government should regulate tobacco
      to require full disclosure including information on the likely health
      consequences of inhaling pesticide and additive pyrolysis products.

PMID- 14645950
TI  - The Australian tar derby: the origins and fate of a low tar harm reduction
      programme.
AB  - OBJECTIVE: To document the development of the low tar harm reduction programme in
      Australia, including tobacco industry responses. DATA SOURCES: Tobacco industry
      documents, retail tobacco journals, newspapers, medical journals, and Anti-Cancer
      Council of Victoria (ACCV) newsletters and archival records. STUDY SELECTION:
      Documents on the strategies and knowledge bases of the ACCV, other Australian
      health authorities, and the tobacco industry. RESULTS: The ACCV built a durable
      system for measuring and publicising the tar and nicotine yields of Australian
      cigarettes and influencing their development. The tobacco industry initially
      sought to block the development of this system but later appeared to cooperate
      with it, as is evidenced by the current market dominance of low tar brands.
      However, behind the scenes, the industry used its substantial knowledge advantage
      regarding compensatory smoking and its ability to re-engineer cigarettes to gain
      effective control of the system and subvert the ACCV's objectives. CONCLUSIONS:
      Replacement of the low tar programme with new means of minimising the harms from
      cigarette smoking should be a policy priority for the Australian government. This
      will require regulation, rather than further voluntary agreements, and stringent
      monitoring of successor programmes will be necessary.

PMID- 14645952
TI  - The Australian cigarette brand as product, person, and symbol.
AB  - OBJECTIVE: To examine, for dominant Australian cigarette brands, brand identity
      (overriding brand vision), brand positioning (brand identity elements
      communicated to the consumer), brand image (consumers' brand perceptions) and
      brand equity (financial value). DESIGN: Tobacco industry documents, articles from
      retail trade publications since 1990, and current brand advertising from retail
      trade publications were searched for information about Australian brands.
      RESULTS: Cigarette manufacturers benefit from their competitors' brand equity as
      well as their own. The industry sees Australian smokers as far less brand loyal
      and strongly oriented to "low tar". A few predominantly local brands dominate the
      market, with variation by state. Successful Australian brands exist in one of
      three categories: premium, mainstream, and supervalue. Their brand identity
      essence is as follows. Premium: quality. Mainstream: a good humoured "fair go"
      for ordinary Australians. Supervalue: value for money. All supervalue brand
      identities also include freedom, escape, mildness, an aspirational attitude, blue
      tones, and waterside scenes. Brand image and brand identity is frequently
      congruent, even when marketing is restricted, and brand image is generally more
      positive for a smoker's own brand. CONCLUSIONS: Tobacco control activities have
      undermined cigarette brand equity. Further research is needed regarding brand
      loyalty, low tar, and brand categories. Smokers may respond more positively to
      tobacco control messages consistent with the identities of their chosen brand,
      and brand-as-organisation elements may assist. Further marketing restrictions
      should consider all elements of brand identity, and aim to undermine brand
      categories.

PMID- 14645951
TI  - From legitimate consumers to public relations pawns: the tobacco industry and
      young Australians.
AB  - OBJECTIVE: To document the Australian tobacco industry's activities regarding
      youth smoking to support tobacco control. METHOD: 492 industry documents from
      primary and secondary websites were abstracted and analysed. RESULTS: Australian
      legislation and rhetoric on youth and tobacco has changed dramatically over the
      last 50 years, from an unproblematic association of teenagers and smoking in the
      1960s, through the industry's aggressive attacks and denials in the 1980s, to the
      1990s, when industry became newly compliant with "societal expectations" and
      youth became a dominant bargaining issue in the industry's public relations
      strategy. The industry's current policy is to simultaneously blame others for
      underage smoking, frame the industry as socially responsible via voluntary
      marketing codes, youth access programmes, and school education, and market
      actively to young adults. CONCLUSIONS: The arbitrary distinction between 17 and
      18 year olds is, particularly in Australia's dark market, a liability for tobacco
      control and an opportunity for the industry, which is attempting to claim the
      high moral ground traditionally occupied by tobacco control on the youth issue.
      The current review of Australia's Tobacco Advertising Prohibition Act of 1992
      should prohibit all forms of industry communication targeting young people,
      including retail access and schools programmes and below-the-line marketing.
      Tobacco control advocacy should highlight the industry's attempts to use the
      youth issue in its own favour while laying the blame elsewhere.

PMID- 14645953
TI  - Going below the line: creating transportable brands for Australia's dark market.
AB  - OBJECTIVE: To investigate non-point-of-sale cigarette marketing in Australia, one
      of the "darkest" markets in the world. DESIGN: Analysis of 172 tobacco industry
      documents. RESULTS: The tobacco industry has continued to market their products
      despite severe restrictions on legal marketing activity. They made careful plans
      to circumvent regulation well in advance. In preparation for bans, they chose and
      strengthened existing brands to enable their continued success in a dark market
      and prepared the consumer for bans by increasing their spending on below the line
      activities. Bans reduced the industry's effectiveness and efficiency. After bans
      new brand launches stopped: instead key existing brands were strengthened via
      alterations to the product, line extensions, and stretching loopholes in the
      legislation as far as possible. In line with the general trend towards integrated
      marketing, a range of activities have been used in combination, including
      guerrilla marketing, advertising in imported international magazines, altering
      the pack, sponsorships, brand stretching, event promotions, lifestyle premiums,
      and the development of corporate websites. CONCLUSIONS: The tobacco industry
      acknowledges that marketing restrictions have an impact, validating their
      continued use in tobacco control. The industry is extremely creative in
      circumventing these marketing restrictions, requiring tobacco marketing
      regulations to be informed by marketing expertise, regularly updated, and to
      adopt the broadest possible scope. Tobacco control advocates, particularly those
      communicating with young people, could learn from the creativity of the tobacco
      industry.

PMID- 14645954
TI  - New frontier, new power: the retail environment in Australia's dark market.
AB  - OBJECTIVE: To investigate the role of the retail environment in cigarette
      marketing in Australia, one of the "darkest" markets in the world. DESIGN:
      Analysis of 172 tobacco industry documents; and articles and advertisements found
      by hand searching Australia's three leading retail trade journals. RESULTS: As
      Australian cigarette marketing was increasingly restricted, the retail
      environment became the primary communication vehicle for building cigarette
      brands. When retail marketing was restricted, the industry conceded only
      incrementally and under duress, and at times continues to break the law. The
      tobacco industry targets retailers via trade promotional expenditure, financial
      and practical assistance with point of sale marketing, alliance building, brand
      advertising, and distribution. Cigarette brand advertising in retail magazines
      are designed to build brand identities. Philip Morris and British American
      Tobacco are now competing to control distribution of all products to retailers,
      placing themselves at the heart of retail business. CONCLUSIONS: Cigarette
      companies prize retail marketing in Australia's dark market. Stringent point of
      sale marketing restrictions should be included in any comprehensive tobacco
      control measures. Relationships between retailers and the industry will be more
      difficult to regulate. Retail press advertising and trade promotional expenditure
      could be banned. In-store marketing assistance, retail-tobacco industry alliance
      building, and new electronic retail distribution systems may be less amenable to
      regulation. Alliances between the health and retail sectors and financial support
      for a move away from retail dependence on tobacco may be necessary to effect
      cultural change.

PMID- 14645955
TI  - "Conclusions about exposure to ETS and health that will be unhelpful to us": how
      the tobacco industry attempted to delay and discredit the 1997 Australian
      National Health and Medical Research Council report on passive smoking.
AB  - BACKGROUND: Major reviews of the health effects of passive smoking have been
      subjected to tobacco industry campaigns to refute the scientific evidence.
      Following the 1992 US Environmental Protection Agency review, the Australian
      National Health and Medical Research Council (NHMRC) initiated a review of the
      health effects of passive smoking. At the time of this review, evidence that
      environmental tobacco smoke causes disease was being increasingly accepted in
      courts of law and voluntary adoption of smoking restrictions was rapidly growing.
      OBJECTIVE: To demonstrate how the tobacco industry attempted to delay and
      discredit the publication of a report on passive smoking that the tobacco
      industry anticipated to contain recommendations that would be unfavourable to
      their business. METHODS: A search of tobacco industry documents on the Master
      Settlement Agreement websites was conducted using the terms and acronyms
      representative of the NHMRC review. RESULTS: The tobacco industry sought to
      impede the progress of the NHMRC Working Party by launching an intensive campaign
      to delay and discredit the report. The main strategies used were attempts to
      criticise the science, extensive use of Freedom of Information provisions to
      monitor all activity of the group, legal challenges, ad hominem attacks on the
      credibility of the Working Party members, rallying support from industry allies,
      and influencing public opinion through the media. CONCLUSIONS: The Australian
      tobacco industry deliberately impeded the NHMRC Working Party's progress and
      successfully prevented the publication of the report's recommendations. The
      tobacco industry's motivation and capacity to disrupt the advancement of
      scientific knowledge and policy in tobacco control should be recognised and
      anticipated.

PMID- 14645956
TI  - "Can't stop the boy": Philip Morris' use of Healthy Buildings International to
      prevent workplace smoking bans in Australia.
AB  - OBJECTIVE: To document the relationship of the indoor air consultancy company
      Healthy Buildings International (HBI) with the Australian tobacco industry.
      DESIGN: Systematic keyword and opportunistic website searches of tobacco industry
      internal documents made available through the Master Settlement Agreement.
      RESULTS: Since 1987 HBI has played a high profile role in advancing the
      Australian tobacco industry's concerns to prevent building owners introducing
      smoke-free workplaces by advocating for ventilation solutions. HBI invoiced
      Philip Morris' US lawyers Covington and Burling for work undertaken in Australia
      and sought to publicly deny its association with the industry. HBI breached
      Standards Australia protocols in providing PM with confidential public
      submissions made to a review of the Australian standard on ventilation and acted
      as an undeclared cipher into the review for Philip Morris's concerns, leading to
      the eventual dismissal of the HBI representative from the standards subcommittee.
      CONCLUSIONS: HBI in Australia exemplifies the tobacco industry's use of third
      party strategy in publicly advancing a case against smoke-free indoor air.

PMID- 14645957
TI  - Outcome measures in chronic obstructive pulmonary disease (COPD).

PMID- 14645958
TI  - Asthma and obesity: where are we now?

PMID- 14645959
TI  - Air pollution and lung cancer: what more do we need to know?

PMID- 14645960
TI  - Hypothesis: ill health associated with low concentrations of nitrogen dioxide--an
      effect of ultrafine particles?

PMID- 14645962
TI  - Calcifying fibrous pseudotumour of the lung.

PMID- 14645964
TI  - Predictors of mortality in alpha1-antitrypsin deficiency.
AB  - BACKGROUND: Lung density measurements by computed tomography have previously been
      found to be a more sensitive indicator of disease progression in emphysema of
      alpha(1)-antitrypsin deficiency than lung function measurements. The aim of this
      study was to investigate the predictive potential of several parameters,
      including CT scanning, for mortality in patients with severe alpha(1)-antitrypsin
      deficiency. METHODS: Over a 5 year period, 256 patients with alpha(1)-antitrypsin
      deficiency (PiZ phenotype) were assessed, of whom 254 underwent lung function
      testing and 197 had thoracic CT scans. Lung function, CT scans, health status (St
      George's Respiratory Questionnaire, SGRQ), and other clinical data of survivors
      and non-survivors were compared and these parameters were applied to survival
      analyses. RESULTS: There were 22 deaths in this patient cohort, 10 of which were
      classified as "respiratory" deaths. Baseline lung function parameters (forced
      expiratory volume in 1 second (FEV(1)), carbon monoxide transfer coefficient
      (KCO)), and CT scores were significantly lower in the non-survivors than in the
      survivors. 170 of the 256 patients had complete data for entry into multiple
      regression analyses (Cox proportional hazards model). In the univariate analysis,
      upper zone expiratory scan had the best association with all cause (p = 0.001)
      and respiratory mortality (p<0.001), whereas FEV(1) (p = 0.158 all cause, 0.015
      respiratory) and KCO (p = 0.002 all cause, 0.012 respiratory) had poorer
      associations with mortality. Only age gave further independent predictive
      information regarding all cause or respiratory mortality when the CT scan was
      entered into the survival analyses. CONCLUSIONS: CT scanning predicts respiratory
      and all cause mortality in alpha(1)-antitrypsin deficiency and appears to be
      superior to lung function parameters, especially FEV(1).

PMID- 14645966
TI  - Correlation between annual change in health status and computer tomography
      derived lung density in subjects with alpha1-antitrypsin deficiency.
AB  - BACKGROUND: There is increasing recognition that questionnaires of health status
      and lung density measurements are more sensitive tools for assessing progression
      of emphysema than forced expiratory volume in 1 second (FEV(1)) and transfer
      coefficient (KCO). A study was undertaken to investigate prospectively the
      correlation between annual change in health status and computer tomography (CT)
      derived lung density in subjects with alpha(1)-antitrypsin deficiency. METHODS:
      Twenty two patients of mean (SD) age 40.7 (9.2) years with ZZ type alpha(1)
      antitrypsin deficiency were investigated at baseline and 30 months later by
      FEV(1) and KCO, St George Respiratory Questionnaire (SGRQ), and by a spiral CT
      scan of the chest. CT data of chest images were analysed using software designed
      for automated lung contour detection and lung density measurements. The density
      data were corrected for changes in inspiration levels. RESULTS: Changes in lung
      density, expressed as 15th percentile point or relative area below -950 HU,
      correlated well with changes in health status (SGRQ total score): R = -0.56, p =
      0.007 or R = 0.6, p = 0.003. Neither changes in health status nor changes in lung
      density correlated significantly with changes in FEV(1) or changes in KCO.
      CONCLUSIONS: The SGRQ total score (which is a global measure in COPD) and lung
      density (a specific measure of emphysema) are sensitive to deterioration in
      patients with alpha(1)-antitrypsin deficiency. This finding may facilitate future
      studies with new drugs specific for emphysema, a frequently occurring component
      of COPD.

PMID- 14645967
TI  - Asthma and atopy in overweight children.
AB  - BACKGROUND: Obesity may be associated with an increase in asthma and atopy in
      children. If so, the effect could be due to an effect of obesity on lung volume
      and thus airway hyperresponsiveness. METHODS: Data from 5993 caucasian children
      aged 7-12 years from seven epidemiological studies performed in NSW were
      analysed. Subjects were included if data were available for height, weight, age,
      skin prick test results to a common panel of aeroallergens, and a measure of
      airway responsiveness. History of doctor diagnosed asthma, wheeze, cough, and
      medication use was obtained by questionnaire. Recent asthma was defined as a
      doctor diagnosis of asthma ever and wheeze in the last 12 months. Body mass index
      (BMI) percentiles, divided into quintiles per year age, were used as a measure of
      standardised weight. Dose response ratio (DRR) was used as a measure of airway
      responsiveness. Airway hyperresponsiveness was defined as a DRR of >/=8.1.
      Adjusted odds ratios were obtained by logistic regression. RESULTS: After
      adjusting for atopy, sex, age, smoking and family history, BMI was a significant
      risk factor for wheeze ever (OR = 1.06, p = 0.007) and cough (OR = 1.08, p =
      0.001), but not for recent asthma (OR = 1.02, p = 0.43) or airway
      hyperresponsiveness (OR = 0.97 p = 0.17). In girls a higher BMI was significantly
      associated with higher prevalence of atopy (chi(2) trend 7.9, p = 0.005), wheeze
      ever (chi(2) trend 10.4, p = 0.001), and cough (chi(2) trend 12.3, p<0.001).
      These were not significant in boys. CONCLUSIONS: Higher BMI is a risk factor for
      atopy, wheeze ever, and cough in girls only. Higher BMI is not a risk factor for
      asthma or airway hyperresponsiveness in either boys or girls.

PMID- 14645968
TI  - Association of body mass with pulmonary function in the Childhood Asthma
      Management Program (CAMP).
AB  - BACKGROUND: While increases in body mass index (BMI) have been associated with
      the incidence and prevalence of asthma, the mechanisms behind this association
      are unclear. METHODS: We hypothesised that BMI would be independently associated
      with measures of asthma severity in a population of children with mild to
      moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). A
      multivariable baseline cross sectional analysis of BMI with our outcomes of
      interest was performed. RESULTS: BMI was generally not associated with symptoms,
      nor was it associated with atopy. While BMI was positively associated with the
      methacholine concentration that causes a 20% fall in forced expiratory volume in
      1 second (PC(20)FEV(1)), this association did not persist after adjustment for
      FEV(1). Increasing BMI was associated with increasing FEV(1) (beta = 0.006 l, 95%
      CI (0.001 to 0.01)) and forced vital capacity (FVC) (beta = 0.012 l, 95% CI
      (0.007 to 0.017)). However, decrements in the FEV(1)/FVC ratio were noted with
      increasing BMI (beta = -0.242, 95% CI (-0.118 to -0.366)). Thus, an increase in
      BMI of 5 units was associated with a decrease in FEV(1)/FVC of over 1%.
      CONCLUSIONS: Although the association of FEV(1) and FVC with BMI did not support
      our initial hypothesis, the decrease noted in the FEV(1)/FVC ratio has potential
      relevance in the relationship between BMI and asthma severity.

PMID- 14645970
TI  - Perception of airway narrowing during reduction of inhaled corticosteroids and
      asthma exacerbation.
AB  - BACKGROUND: The perception of airway narrowing is reduced in subjects with severe
      asthma and may be related to the severity of airway inflammation. A study was
      undertaken to determine if the perception of airway narrowing changes during the
      reduction of inhaled corticosteroid (ICS) dose or during an asthma exacerbation.
      METHODS: Forty two asthmatic subjects with well controlled asthma had their daily
      ICS dose halved every 2 months until they were weaned off ICS or they developed
      an exacerbation. Perception was measured at baseline and at monthly intervals
      during bronchial challenge with mannitol as the slope and intercept of the
      regression of the Borg score and percentage fall in forced expiratory volume in 1
      second (FEV(1)), and as the Borg score at 20% fall in FEV(1) (PS(20)FEV(1)).
      Sputum was collected for measurement of inflammatory cell numbers. RESULTS: In 33
      subjects who successfully halved their ICS dose without exacerbation there were
      significant reductions in slope (p = 0.01), intercept (p = 0.01), and
      PS(20)FEV(1) (p = 0.003). Sputum eosinophils and airway hyperresponsiveness
      increased significantly but, in 14 subjects from whom sputum was obtained,
      changes in eosinophils were not correlated with changes in perception. Change in
      airway hyperresponsiveness correlated with change in PS(20)FEV(1) (r = -0.40, p =
      0.025). In 27 subjects who developed an exacerbation, slope decreased (p = 0.02)
      and intercept increased (p = 0.01) compared with the visit before the
      exacerbation. Changes in intercept correlated with changes in resting FEV(1) (r =
      -0.57, p = 0.002). CONCLUSIONS: Perception of airway narrowing decreases during
      ICS dose reduction and decreases further during a mild asthma exacerbation. These
      changes are related to concurrent changes in airway hyperresponsiveness and
      resting lung function. The effect of changes in airway inflammation on perception
      is unclear.

PMID- 14645971
TI  - Exhaled nitric oxide and asthma: complex interactions between atopy, airway
      responsiveness, and symptoms in a community population of children.
AB  - BACKGROUND: Exhaled nitric oxide (FE(NO)) is raised in asthmatic children, but
      there are inconsistencies in the relationship between FE(NO) and characteristics
      of asthma, including atopy, increased airway responsiveness (AR), and airway
      inflammation. The aim of this study was to investigate the relationship between
      FE(NO) and asthma, atopy, and increased AR in children. METHODS: One hundred and
      fifty five children (79 boys) of mean age 11.5 years underwent an assessment that
      included FE(NO) measurements, spirometric tests, inhaled histamine challenge, and
      a skin prick test. Blood was collected for eosinophil count. Current and past
      asthma like symptoms were determined by questionnaire. RESULTS: In multiple
      linear regression analyses FE(NO) was associated with atopy (p<0.001), level of
      AR (p = 0.005), blood eosinophil count (p = 0.007), and height (p = 0.002) but
      not with physician diagnosed asthma (p = 0.1) or reported wheeze in the last 12
      months (p = 0.5). Separate regression models were conducted for atopic and non
      atopic children and associations between FE(NO) and AR, blood eosinophils and
      height were only evident in atopic children. Exhaled NO was raised in children
      with a combination of atopy and increased AR independent of symptoms. CONCLUSION:
      Raised FE(NO) seems to be associated with an underlying mechanism linking atopy
      and AR but not necessarily respiratory symptoms.

PMID- 14645972
TI  - The safety and quality of endobronchial biopsy in children under five years old.
AB  - BACKGROUND: Little is known about the airway pathology of wheezing disorders in
      infants and preschool children, partly owing to the difficulty of undertaking
      invasive studies in this age group. The safety of endobronchial biopsy and the
      quality of biopsies obtained were reviewed in infants and preschool children.
      METHODS: Case notes of children under five years of age who underwent
      bronchoscopy and endobronchial biopsy were reviewed. The safety of the procedure
      was compared in a control group matched for weight and age, undergoing
      bronchoscopy without endobronchial biopsy. A consultant histopathologist assessed
      biopsy quality. RESULTS: 33 patients (mean age 31 months, range 4 to 59)
      underwent bronchoscopy and endobronchial biopsy, and were matched with 33
      controls (mean age 28 months, range 3 to 52). There was no significant difference
      between groups in the number, type, or severity of complications occurring during
      or after the procedure. Biopsies from 30 of the 33 subjects could be assessed.
      Reticular basement membrane was identified in all 30; inflammation could be
      assessed in 26; areas of smooth muscle were present in 23. CONCLUSIONS: In a
      group of preschool children undergoing bronchoscopy under general anaesthetic,
      performance of endobronchial biopsy carried no extra risk. The quality of
      biopsies obtained was usually sufficient to allow an assessment of remodelling
      and inflammation.

PMID- 14645975
TI  - Safety of endobronchial biopsy in 170 children with chronic respiratory symptoms.
AB  - BACKGROUND: There is a paucity of bronchial biopsy data in children. A major
      limitation is concern over the safety of the procedure. This paper reports the
      results of efforts to develop a method that is safe and provides adequate
      specimen for evaluation. METHODS: 170 children aged 2.5 to 16 years with chronic
      respiratory symptoms were studied under general anaesthesia in an outpatient
      surgery setting. Bronchoalveolar lavage and biopsies were obtained using a 4.9 mm
      flexible bronchoscope through a laryngeal mask airway. At least three bioipsies
      were taken. RESULTS: No patient required topical adrenaline to control bleeding,
      nor was there a change in the state of any of the patients. There were no
      episodes of pneumothorax, haemoptysis, pneumonia, or significant fever. All
      children less than four years old received a single dose of antibiotic
      intravenously after the procedure. The average length of time for the procedure
      was 12 minutes (range 6 to 27). Recovery time averaged 90 minutes. The limiting
      factor was the ability of the child's airway to accomodate the bronchoscope.
      CONCLUSIONS: This report should encourage clinicians to incorporate endobronchial
      biopsy into the evaluation of children with difficult respiratory problems.

PMID- 14645976
TI  - Relationship between birth weight and adult lung function: controlling for
      maternal factors.
AB  - BACKGROUND: There is conflicting evidence on the "fetal origins hypothesis" of
      association between birth weight and adult lung function. This may be due to
      failure to control for confounding maternal factors influencing birth weight. In
      the present study access to birth details for adults aged 45-50 years who were
      documented as children to have asthma, wheezy bronchitis, or no respiratory
      symptoms provided an opportunity to investigate this association, controlling for
      maternal factors. METHODS: In 2001 the cohort was assessed for current lung
      function, smoking status, and respiratory symptoms. Birth details obtained from
      the Aberdeen Maternity and Neonatal Databank recorded birth weight, gestation,
      parity, and mother's age and height. RESULTS: 381 subjects aged 45-50 years were
      traced and tested for lung function; 323 (85%) had birth details available. A
      significant linear trend (p<0.01) was observed between birth weight and current
      forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC)
      values (adjusted for height, age, sex, weight, deprivation category (Depcat),
      childhood group, and smoking status). This trend remained significant after
      adjusting birth weight for gestation, parity, sex, mother's height and weight (p
      = 0.01). The relationship between birth weight and FEV(1) and FVC remained
      significant when adjusted for smoking history. There was no association between
      birth weight and current wheezing symptoms. CONCLUSION: There is a positive
      linear trend between birth weight, adjusted for maternal factors, and lung
      function in adulthood. The strength of this association supports the "fetal
      origins hypothesis" that impairment of fetal growth is a significant influence on
      adult lung function.

PMID- 14645977
TI  - Idiopathic chronic cough: association with organ specific autoimmune disease and
      bronchoalveolar lymphocytosis.
AB  - BACKGROUND: We have recently reported a strong association between organ specific
      autoimmune disease and idiopathic chronic cough and have suggested that cough may
      be caused by airway inflammation secondary to aberrant homing of activated
      lymphocytes to the lung. An immunopathological study was undertaken to test the
      hypothesis that idiopathic chronic cough is associated with lymphocytic airway
      inflammation. METHODS: Bronchoscopy, bronchial biopsies, bronchoalveolar lavage
      (BAL), and peripheral blood and BAL flow cytometry were performed in 19 patients
      with idiopathic chronic cough, 14 with explained chronic cough, and 11 normal
      subjects. RESULTS: Organ specific autoimmune disease or positive autoantibodies
      were present in eight of the 19 patients with idiopathic cough, in one of the 14
      patients with explained cough, and in one of the 11 normal subjects. Median BAL
      fluid differential lymphyocyte counts were significantly higher in patients with
      idiopathic cough (10.0%) than in normal subjects (6.3%, 95% confidence interval
      of difference 1.5 to 11.9, p = 0.01) or patients with explained cough (5.2%, 95%
      CI of difference 2.0 to 10.4, p = 0.001). There were no differences in bronchial
      biopsy T lymphocyte counts between the groups. The mean (SE) proportion of CD3+
      peripheral blood mononuclear cells expressing CD4 was significantly higher in
      normal subjects than in patients with idiopathic cough (69 (3)% v 58 (3)%, mean
      difference 11%, 95% CI of difference 2 to 20, p<0.02) but not than those with
      explained chronic cough (63 (2)%). There were no differences in BAL T lymphocyte
      phenotype between groups. CONCLUSION: BAL fluid lymphocytosis occurs in some
      patients with idiopathic chronic cough. The association of idiopathic chronic
      cough with organ specific autoimmune disease raises the possibility that this
      might be caused by lymphocyte homing from the primary site of autoimmune
      inflammation or the result of an autoimmune process in the lung.

PMID- 14645978
TI  - Lung cancer and air pollution: a 27 year follow up of 16 209 Norwegian men.
AB  - BACKGROUND: The well documented urban/rural difference in lung cancer incidence
      and the detection of known carcinogens in the atmosphere have produced the
      hypothesis that long term air pollution may have an effect on lung cancer. The
      association between incidence of lung cancer and long term air pollution exposure
      was investigated in a cohort of Oslo men followed from 1972/73 to 1998. METHODS:
      Data from a follow up study on cardiovascular risk factors among 16 209 40 to 49
      year old Oslo men in 1972/73 were linked to data from the Norwegian cancer
      register, the Norwegian death register, and estimates of average yearly air
      pollution levels at the participants' home address in 1974 to 1998. Survival
      analyses, including Cox proportional hazards regression, were used to estimate
      associations between exposure and the incidence of lung cancer. RESULTS: During
      the follow up period, 418 men developed lung cancer. Controlling for age, smoking
      habits, and length of education, the adjusted risk ratio for developing lung
      cancer was 1.08 (95% confidence interval, 1.02 to 1.15) for a 10 micro g/m(3)
      increase in average home address nitrogen oxide (NO(x)) exposure between 1974 and
      1978. Corresponding figures for a 10 micro g/m(3) increase in sulphur dioxide
      (SO(2)) were 1.01 (0.94 to 1.08). CONCLUSIONS: Urban air pollution may increase
      the risk of developing lung cancer.

PMID- 14645979
TI  - Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake
      in malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma is an aggressive neoplasm with a
      highly variable course. This pilot study evaluated the significance of the
      pattern, intensity and kinetics of 18F-FDG uptake in mesothelioma in the context
      of histopathology and surgical staging. METHODS: Sixteen consecutive patients
      with pleural disease on CT scan underwent 18F-FDG imaging. Imaging was performed
      with a dual detector gamma camera operating in coincidence mode. Semiquantitative
      image analysis was performed by obtaining lesion-to-background ratios (18F-FDG
      uptake index) and calculating the increment of 18F-FDG lesion uptake over time
      (malignant metabolic potential index (MMPi)). RESULTS: Twelve patients had
      histologically proven malignant mesotheliomas (10 epithelial, two sarcomatoid).
      Thirty two lesions were positive for tumour. Patterns of uptake matched the
      extent of pleural and parenchymal involvement observed on CT scanning and
      surgery. Mean (SD) 18F-FDG uptake index for malignant lesions was 3.99 (1.92),
      range 1.5-9.46. Extrathoracic spread and metastases had higher 18F-FDG uptake
      indices (5.17 (2)) than primary (3.42 (1.52)) or nodal lesions (2.99 (1)). No
      correlation was found between histological grade and stage. The intensity of
      lesion uptake had poor correlation with histological grade but good correlation
      with surgical stage. 18F-FDG lesion uptake increased over time at a higher rate
      in patients with more advanced disease. The MMPi was a better predictor of
      disease aggressiveness than the histological grade. CONCLUSIONS: This pilot study
      suggests that the pattern, intensity, and kinetics of 18F-FDG uptake in
      mesothelioma are good indicators of tumour aggressiveness and are superior to the
      histological grade in this regard.

PMID- 14645981
TI  - Preliminary experience with a new method of endoscopic transbronchial real time
      ultrasound guided biopsy for diagnosis of mediastinal and hilar lesions.
AB  - BACKGROUND: The aim of the present study was to gain experience with a new method
      of endoscopic transbronchial ultrasonography with direct, real time guided fine
      needle aspiration biopsy (EBUS-FNA). METHODS: EBUS-FNA was performed in 11
      patients. Selection of the patients for EBUS-FNA was based on computed
      tomographic (CT) scanning in 10 patients and on positron emission tomography in
      one. The ultrasonic bronchoscope used was a prototype with an outer diameter of
      6.9 mm. The instrument has a small curved array transducer located in front of a
      30 degrees oblique forward viewing optic lens and a biopsy channel of 2 mm. The
      procedures were performed under general anaesthesia. EBUS-FNA was performed by
      direct transducer contact with the trachea or main bronchi with a prototype 22
      gauge needle. RESULTS: A total of 15 lesions were punctured. No complications
      were experienced. Four lesions were targeted in region 10L, four in region 10R,
      one in region 4L, three in region 4R, one in region 1, one in region 7, and one
      in region 2R. The size of the lesions ranged from 7 mm to 80 mm. EBUS-FNA
      identified malignant cells in 13 lesions and benign cells in two. CONCLUSIONS:
      EBUS-FNA is a promising technique for lymph node staging of lung cancer as well
      as for the primary diagnosis of solid lesions located adjacent to the trachea and
      main bronchi and not accessible by other methods apart from surgical
      intervention.

PMID- 14645982
TI  - Burkholderia pseudomallei: another emerging pathogen in cystic fibrosis.
AB  - BACKGROUND: Burkholderia pseudomallei is an important cause of acute fulminant
      pneumonia and septicaemia in tropical regions of northern Australia and south
      east Asia. Subacute and chronic forms of the disease also occur. There have been
      three recent reports of adults with cystic fibrosis (CF) who presumably acquired
      B pseudomallei infection during extended vacations or residence in either
      Thailand or northern Australia. METHODS: The clinical course, molecular
      characteristics, serology and response to treatment are described in four adult
      CF patients infected with B pseudomallei. Polymerase chain reaction (PCR) based
      methods were used to confirm B pseudomallei and exclude B cepacia complex.
      Genotyping was performed using randomly amplified polymorphic DNA (RAPD) PCR and
      pulsed field gel electrophoresis (PFGE). RESULTS: Four patients are described
      with a mean duration of infection of 32 months. All but one patient lived in
      tropical Queensland. Two patients (with the longest duration of infection)
      deteriorated clinically and one subsequently died of respiratory failure. Both
      responded to intravenous treatment specifically targeting B pseudomallei. Another
      patient suffered two severe episodes of acute bronchopneumonia following
      acquisition of B pseudomallei. Eradication of the organism was not possible in
      any of the cases. PFGE of a sample isolate from each patient revealed the strains
      to be unique and RAPD analysis showed retention of the same strain within an
      individual over time. CONCLUSIONS: These findings support a potential pathogenic
      role for B pseudomallei in CF lung disease, producing both chronic infection and
      possibly acute bronchopneumonia. Identical isolates are retained over time and
      are unique, consistent with likely environmental acquisition and not person to
      person spread. B pseudomallei is emerging as a significant pathogen for patients
      with CF residing and holidaying in the tropics.

PMID- 14645983
TI  - Cough. 3: chronic cough and gastro-oesophageal reflux.
AB  - The pathogenesis and clinical features of gastro-oesophageal reflux related cough
      are complex and the diagnostic tests available are of limited reliability.
      Treatment needs to be tailored to the specific needs of individual patients and
      other possible causes of chronic cough should be investigated. Treatment should
      only be considered to have failed when cough persists after administration of
      proton pump inhibitors at an adequate dosage for a sufficient length of time.

PMID- 14645984
TI  - Underlying chronic granulomatous disease in a patient with bronchocentric
      granulomatosis.
AB  - We present a case of bronchocentric granulomatosis in a woman with no history of
      asthma who was colonised with Aspergillusfumigatus. A family history of chronic
      granulomatous disease prompted further testing that demonstrated severely
      depressed neutrophil oxidant production and gp91(phox) deficiency compatible with
      the X linked carrier state of chronic granulomatous disease. Only one report of
      the association of these two rare diseases has previously appeared in the
      literature. We postulate that an ineffective immune response led to the prolonged
      colonisation of Afumigatus resulting in a hypersensitivity reaction that was
      manifest clinically as bronchocentric granulomatosis.

PMID- 14645985
TI  - Brain N-acetylaspartate as a molecular water pump and its role in the etiology of
      Canavan disease: a mechanistic explanation.
AB  - N-acetyl-L-aspartate (NAA), an abundant amino acid present in the vertebrate
      brain, is synthesized and stored primarily in neurons. Its metabolism is also
      dynamic, with NAA turning over more than once each day by its regulated efflux
      into extracellular fluid (ECF), cycling between an anabolic L-aspartate
      acetylating compartment in neurons and a catabolic NAA deacetylating compartment
      in oligodendrocytes. An inborn error in NAA metabolism results in Canavan disease
      (CD), a rare and usually fatal early-onset autosomal recessive human central
      nervous system (CNS) disease, caused by failure of the catabolic metabolism of
      NAA resulting from a lack of sufficient amidohydrolase II activity in
      oligodendrocytes. Various hypotheses regarding the metabolism of NAA and its role
      have been considered, and although NAA may perform several functions in the CNS,
      an important role of NAA appears to be osmoregulatory. Based on this role, an
      osmotic-hydrostatic mechanism for the etiology of the CD phenotype is proposed.
      In CD, the daily addition of 13375 Pascals (0.132 atmospheres or 1.94 lbs per
      square inch) of hydrostatic pressure to brain ECF, on the brain cell side of
      brain-barrier epithelial membranes, resulting from the continuous synthesis and
      efflux of NAA, is considered to be responsible for the syndrome.

PMID- 14645986
TI  - Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor
      against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) mouse model of Parkinson's disease.
AB  - There is evidence that both inflammatory mechanisms and mitochondrial dysfunction
      contribute to Parkinson's disease (PD) pathogenesis. We investigated whether the
      cyclooxygenase 2 (COX-2) inhibitor rofecoxib either alone or in combination with
      creatine could exert neuroprotective effects in the 1-methyl-4-phenyl-1,2,3, 6
      tetrahydropyridine model of PD in mice. Both rofecoxib and creatine administered
      alone protected against striatal dopamine depletions and loss of substantia nigra
      tyrosine hydroxylase immunoreactive neurons. Administration of rofecoxib with
      creatine produced significant additive neuroprotective effects against dopamine
      depletions. These results suggest that a combination of a COX-2 inhibitor with
      creatine might be a useful neuroprotective strategy for PD.

PMID- 14645987
TI  - Endotoxin-induced changes in human working and declarative memory associate with
      cleavage of plasma "readthrough" acetylcholinesterase.
AB  - Endotoxin stimulation of the immune system produces marked alterations in memory
      functioning. However, molecular links between this cognitive response and
      infection-responding neurotransmission pathways are still unknown. The cytokine
      and memory responses of volunteers injected with 0.8 ng/kg Salmonella endotoxin
      were compared with changes in plasma levels and integrity of the stress-induced
      acetylcholinesterase variant, AChE-R. Vascular endothelial cells were found to
      express AChE-R messenger RNA and protein both in healthy and inflamed human
      tissues. Plasma AChE activity was reduced after endotoxin treatment, but not
      placebo treatment, parallel to the decline in cortisol after the endotoxin
      induced peak and inversely to the accumulation of a C-terminal immunopositive
      AChE-R peptide of 36 amino acid residues. AChE-R cleavage coincided with
      significant endotoxin-induced improvement in working memory and impairment in
      declarative memory. By 3 h posttreatment, working memory improvement was
      negatively correlated with AChE-R cleavage, which showed association to
      proinflammatory cytokine levels. By 9 h posttreatment, declarative memory
      impairment was negatively correlated with AChE-R cleavage and positively
      correlated with the suppressed AChE activity. Endotoxin-induced peripheral
      cholinergic stress responses are hence associated with greater impairment in
      declarative memory and lower improvement in working memory, pointing at AChE-R as
      a surrogate marker of psychoneuroimmunological stress.

PMID- 14645988
TI  - Glutamate receptors communicate with Na+/K+-ATPase in rat cerebellum granule
      cells: demonstration of differences in the action of several metabotropic and
      ionotropic glutamate agonists on intracellular reactive oxygen species and the
      sodium pump.
AB  - Two glutamate receptor agonists, NMDA (N-methyl-D-aspartic acid) and ACPD (cis
      (1S/3R)-1-aminocyclopentane- 1,3-dicarboxylic acid), induce the reactive oxygen
      species (ROS) production in rat cerebellum granule cells, whereas the third one,
      3-HPG (3-hydroxyphenylglycine), decreases this parameter. The simultaneous
      presence of 3-HPG, together with NMDA or ACPD, prevents the generation of ROS by
      neuronal cells. A similar effect of these ligands on Na+/K+-ATPase can be
      demonstrated: NMDA and ACPD inhibited the enzyme activity, but 3-HPG activated
      Na+/K+-ATPase and prevented its inhibition by NMDA or ACPD. In terms of current
      classification, NMDA is an agonist of ionotropic glutamate receptors of the so
      called NMDA class, whereas ACPD and 3-HPG belong to metabotropic agonists, the
      former primarily being an activator of metabotropic glutamate receptors (mGluRs)
      of groups 2 and 3, and the latter, that of mGluRs of groups 1 and 5. Thus, the
      data presented illustrate the existence of diverse mechanisms of the cross talk
      between Na+/K+-ATPase and different glutamate receptors, as well as that between
      glutamate receptors of different classes.

PMID- 14645990
TI  - Calpainopathy: how broad is the spectrum of clinical variability?
AB  - Five affected siblings were referred with a probable diagnosis of proximal adult
      type spinal muscular atrophy (SMA) based on lower motor neuron signs (muscle
      weakness and atrophy, hypotony, hypoactive or absent reflexes, and
      fasciculations), normal or borderline serum creatine kinase levels, and a
      neurogenic pattern on electromyography, compatible with motor neuron disease, in
      one patient. No exon 7-8 deletion in the survival motor neuron (SMN) gene was
      found. Linkage analysis excluded the SMN and all known autosomal recessive limb
      girdle muscular dystrophy loci, with the exception of LGMD-2A. A homozygous R769Q
      mutation in the calpain-3 gene and absence of muscle calpain-3 protein confirmed
      a calpainopathy. This family suggests that the clinical spectrum of calpainopathy
      might be broader and that this diagnosis might be considered in patients with an
      atypical motor neuron disease.

PMID- 14645989
TI  - Short-term sleep disturbance enhances brain-derived neurotrophic factor gene
      expression in rat hippocampus by acting as internal stressor.
AB  - Rats were subjected to nonselective sleep disturbance for short periods under
      conditions designed to minimize the adverse influence of external stresses, such
      as environmental conditions and restricted movement, and both brain-derived
      neurotrophic factor (BDNF) protein and its mRNA levels in the brain were then
      determined to investigate the influence of sleep disturbance itself on BDNF gene
      expression. Total sleep duration was partially but significantly reduced by
      disturbing the sleep/wake cycle for 1 and 2 h, gradually increased according to
      the time of disturbance, then returned to control levels at 6 h after the
      beginning of sleep disturbance. Under these conditions, the slight but
      significant elevation of corticotrophin-releasing factor (CRF) mRNA levels in the
      paraventricular nucleus (PVN) was observed at an early stage of the sleep
      disturbance period. Sleep disturbance induced the elevation of both BDNF protein
      and its mRNA levels in the hippocampus but not in the cerebellum or the
      brainstem, and the elevated BDNF mRNA expression in the hippocampus returned
      toward basal levels during the sleep recovery period when the rebound of sleep
      duration was observed. These findings suggest the possibility that short-term
      disturbance of the sleep/wake cycle and, hence, the partial reduction of non-REM
      sleep duration, might exert a potential influence on neuronal and/or glial cells
      as an internal stressor, resulting in the elevation of BDNF gene expression in
      rat hippocampus.

PMID- 14645991
TI  - Serum levels of vitamins A, C, and E, beta-carotene, selenium, and zinc in
      patients with Behcet's disease: a controlled study.
AB  - Behcet's disease is a multisystemic disease characterized by activation and
      remission periods. The etiopathogenesis is not exactly known; a genetic defect in
      the immunoregulatory system induced by infectious agents, like viruses and
      bacteria, is thought to cause the disease. In this study, we examine the serum
      levels of vitamins A, C, and E, beta-carotene, selenium, and zinc in Behcet's
      disease patients and investigate the relationship between these serum levels and
      the activation of the disease. We conclude that adding vitamin E to the treatment
      of Behcet's disease patients and its effects on the prognosis of the disease need
      to be further investigated by controlled studies.

PMID- 14645992
TI  - Levels of zinc and magnesium in senile and diabetic senile cataractous lenses.
AB  - Zinc and magnesium in serum, hair, and lens were determined in diabetic and
      nondiabetic patients who have been operated because of senile cataract. Both
      trace elements were measured by atomic absorption spectrometry, after acidic
      digestion of the lens and hair samples. Although there was no difference in
      serum, lens, and hair levels of magnesium between the two groups, the lens levels
      of zinc in diabetic patients (0.56+/-0.05 micromol/g dry weight) were
      significantly higher as compared with nondiabetic group (0.42+/-0.03 micromol/g
      dry weight). There was no statistically significant difference in serum and hair
      levels of zinc between the groups. The increased concentration of zinc in the
      lens of diabetic patients suggests that zinc might play a role in developmental
      mechanism of the diabetic senile cataract.

PMID- 14645993
TI  - Silicon compatible with the height of human vertebral column.
AB  - In the study on human vertebral composites, silicon was found to be related to
      the height of the vertebral column. The element ratio of silicon to calcium in
      the lumbar vertebra was twice that of the lowest one in the cervical vertebra.
      The element ratio gradually increased from approx 0.5 at the cervical vertebra to
      approx 1.0 at the lumbar one. Silicon is preserved catastropically much more in
      the lower height of the backbone in contrast with the calcium amount, and the
      ratio to sulfur appears to be unchanged. This suggests that silicon is compatible
      with the biokinetics of the vertebral bone structure of calcium.

PMID- 14645994
TI  - Compositional changes of the xiphoid process and costal cartilage with aging.
AB  - To elucidate compositional changes of the cartilage with aging, the authors
      investigated age-related changes of element contents in the xiphoid process and
      costal cartilage by inductively coupled plasma-atomic emission spectrometry.
      After the ordinary dissection by medical students was finished, the xiphoid
      processes and bilateral the fourth costal cartilages were resected and element
      contents were determined. The subjects consisted of 17 men and 9 women, ranging
      in age from 52 to 96 yr. No significant correlations were found between age and
      the content of elements, such as Ca, P, S, Mg, Na, Zn, Fe, and Si in the xiphoid
      process and costal cartilage, except for S in the costal cartilage, in which an
      extremely significant correlation was found. With regard to the relationships
      among element contents, the common finding that there were significant direct
      correlations both between Ca and P contents and between Ca and Mg contents,
      whereas there were significant inverse correlations both between Ca and S
      contents and between P and S contents obtained in the xiphoid process and costal
      cartilage.

PMID- 14645995
TI  - Characterization of the cellular response during apoptosis induction in cadmium
      treated Hep G2 human hepatoma cells.
AB  - Cadmium is a toxic transition heavy metal of continuing occupational and
      environmental concern, with a wide variety of adverse effects on regulation of
      gene expression and cellular signal transduction pathways. Injury to cells by
      cadmium leads to a complex series of events that can culminate in the death of
      the cell. It has been reported that cadmium induces apoptosis in many cell lines.
      However, the morphological characteristics leading to apoptosis or subsequent
      regeneration in cells exposed to cadmium have not been clarified. We evaluated
      whether human hepatoma cells maintained in culture undergo apoptosis when exposed
      to cadmium. Cytotoxic activity of cadmium on Hep G2 cells determined using 3-[4,5
      dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay. A DNA ladder assay
      was performed by electrophoresis. Cell cycle analysis was quantified by flow
      cytometry. Nuclear morphology was studied by fluorescence microscopy after
      staining with propidium iodide and Hoechst 33342. Morphologic alterations in
      culture hepatocytes treated with CdCl2 were observed by transmission electron
      microscopy. We have demonstrated that apoptosis is a major mode of elimination of
      damaged HepG2 cells in cadmium toxicity and it precedes necrosis.

PMID- 14645996
TI  - Numerical methods for estimating iron requirements from population data.
AB  - The estimation of iron requirements is crucial for nutrition and food policy. The
      traditional methods for estimating iron requirements are balance methods based on
      iron intakes and excretions and factorial methods based on estimated iron
      absorption rates and estimated iron losses from body compartments. As an
      alternative, numerical methods for estimating iron requirements from population
      data of iron status were developed. The iron status data reported by Satoh (1991)
      were used in the sixth edition of Recommended Dietary Allowances for Japanese.
      The menstrual iron losses in Japanese premenopausal women were estimated from the
      literature to calculate total iron losses as the sum of basal iron losses and
      menstrual iron losses. The use of this alternative method is illustrated by
      analyzing the same population data comprising the prevalence of iron deficiency
      and the distribution of iron intake. The estimated average requirements were
      affected by the form of distribution function, the relative standard deviation of
      requirements, and the correlation coefficient between iron intakes and
      requirements. We conclude that numerical methods can be very useful for
      estimating iron requirements and to elucidate dietary recommendations of iron.
      These methods may contribute to determining requirements of other nutrients as
      well as iron.

PMID- 14645997
TI  - Comparison of mineral contents between the arteries in upper and lower limbs of
      Japanese monkeys.
AB  - To examine whether the calcium accumulation in aged arteries is related to the
      way of walking, the mineral contents were determined in the arteries of Japanese
      monkeys of quadrupedal walk by inductively coupled plasma-atomic emission
      spectrometry. Sixteen Japanese monkeys consisting of 7 males and 9 females
      ranging in age from 2 to 33 yr were studied. The accumulation of calcium,
      phosphorus, and magnesium occurred progressively in most, but not all, of the
      arteries with aging. It was found that independent of the upper and lower limbs,
      a higher accumulation of calcium, phosphorus, and magnesium occurred in the
      arteries of the proximal regions with aging, compared with the arteries of the
      distal regions. In a comparison between the arteries of anatomically
      corresponding regions of the upper and lower limbs, the accumulation of calcium
      and magnesium was 20-60% higher in the external iliac and femoral arteries of the
      lower limb than in the axillary and brachial arteries of the upper limb.
      Regarding phosphorus, the accumulation was 20-120% higher in the external iliac
      and femoral arteries than in the axillary and brachial arteries. It was known
      that in humans, the accumulation of calcium, phosphorus, and magnesium was three
      to seven times higher in the arteries of the lower limb than in the arteries of
      the upper limb. It is clear that there is a very significant difference in the
      accumulation of calcium and magnesium in the arteries of the lower limbs between
      Japanese monkeys and humans. The present study suggests that the accumulation of
      calcium and magnesium in the arteries of the lower limb with aging is affected by
      the way of walking.

PMID- 14645998
TI  - Influence of lanthanum on the uptake of trace elements in cucumber plant.
AB  - The effects of La3+ on the uptake of trace elements (Se, Co, V, and Tc) in
      cucumber plants were studied by a radioactive multitracer technique. It was
      observed that the uptake and distribution of these trace elements in roots,
      stems, and leaves are different under different La3+ treatments. Furthermore, in
      the control, the plant accumulates 75Se, 56Co, and 48V all in the order
      roots>leaves>stems, whereas 95mTc was in the order leaves>stems>roots. The
      accumulations of 75Se and 95mTc in plants treated with different La3+
      concentration were in the same order as those in the control, but the uptakes
      percentages of other kinds of element changed differently. The results indicate
      that lanthanum treatments to a growing cucumber lead to the change of uptake of
      trace elements, which suggest that a rare earth element is directly or indirectly
      involved in the ion transport of the plant and affects plant growth by regulating
      the uptake and distribution of elements that influence the plant cell physiology
      and biochemistry.

PMID- 14645999
TI  - Independent exponential feeding of glycerol and methanol for fed-batch culture of
      recombinant Hansenula polymorpha DL-1.
AB  - As a novel feeding strategy for optimizing human epidermal growth factor (hEGF)
      production with a recombinant Hansenula polymorpha DL-1 using the methanol
      oxidase (MOX) promoter in H. polymorpha DL-1, independent exponential feeding of
      two substrates was used. A simple kinetic model considering the cell growth on
      two substrates was established and used to calculate the respective feeding rates
      of glycerol and methanol. In the fedbatch culture with methanol-only feeding, the
      optimal set point of specific growth rate on methanol was found to be 0.10 h-1.
      When the fed-batch cultures were conducted by the independent feeding of glycerol
      and methanol, the actual specific growth rate on glycerol and methanol was
      slightly lower than the set point of specific growth rate. By the uncoupled
      feeding of glycerol and methanol the volumetric productivity of hEGF increased
      from 6.4 to 8.0 mg/(L.h), compared with methanol-only feeding.

PMID- 14646000
TI  - Degradation of ferric EDTA by Burkhol cepacia.
AB  - EDTA, the target compound of this study from the effluent of secondary
      biotreatment units, can be biodegraded by special microorganisms. So far, there
      are three species of microorganisms--Agrobacterium, Gram-negative BNCI, and
      DSM9103--that can degrade EDTA and are published in the literature. We have
      successfully isolated a bacterial strain that can degrade EDTA. It was identified
      as Burkhol cepacia, an aerobic species, elliptically shaped with a length of 5-15
      microm. The growth medium contains 1000 mg/L of ferric-EDTA as carbon source, 750
      mg/L of (NH4)2SO4 + (NH2)2CO as nitrogen source, and 1000 mg/L of KH2PO4 as
      phosphorus source, and mineral factors such as Fe and Mg. Incubated at pH 7.0, 30
      degrees C, and 150 rpm on a shaker for 15 d, the average specific growth rate of
      this microbe is 0.135 d-1, which shows that the respective degradation efficiency
      of Fe-EDTA and Cu-EDTA is 90 and 75% individually.

PMID- 14646001
TI  - Conversion of municipal solid wastes to carboxylic acids by thermophilic
      fermentation.
AB  - The purpose of this research is to generate carboxylic acids from the
      biodegradable fraction of municipal solid wastes (MSW) and municipal sewage
      sludge (MSS) by using a thermophilic (55 degrees C), anaerobic, high-solid
      fermentation. With terrestrial inocula, the highest total carboxylic acid
      concentration achieved was 20.5 g/L, the highest conversion obtained was 69%, and
      the highest acetic acid selectivity was 86.4%. Marine inocula were also used to
      compare against terrestrial sources. Continuum particle distribution modeling
      (CPDM) was used to predict the final acid product concentrations and substrate
      conversions at a wide range of liquid residence times (LRT) and volatile solid
      loading rates (VSLR). "Maps" showing the product concentration and conversion for
      various LRT and VSLR were generated from CPDM. The predictions were compared to
      the experimental results. On average, the difference between the predicted and
      experimental values were 13% for acid concentration and 10% for conversion. CPDM
      "maps" show that marine inocula produce higher concentrations than terrestrial
      inocula.

PMID- 14646002
TI  - Activity and survival of spray-dried Beijerinckia sp. microencapsulated in
      different carbohydrates.
AB  - This study examined the possibility of preserving Beijerinckia cultures by
      encapsulation using a spray drier, for use in biotechnological processes in the
      production of biopolymers. An adequate choice of the wall (coating) material is
      one of the factors that will determine the degree of cell survival and the
      maintenance of fermentative activity in the encapsulated inoculum. Malt dextrin,
      dehydrated glucose syrups, modified starch, and acacia (gum arabic) were used as
      wall materials. The results showed that spray-dried Beijerinckia encapsulated in
      malt dextrin, stored for 2 mo, and inoculated into sterile must after rehydration
      presented the greatest stability with respect to fermentative activity, although
      the glucose-encapsulated cells showed the highest percentage of viability during
      spray drying and during the storage period.

PMID- 14646004
TI  - Benchmarking the quality of schizophrenia pharmacotherapy: a comparison of the
      Department of Veterans Affairs and the private sector.
AB  - BACKGROUND: Comparing quality of care between large health care systems is
      important for health systems management. This study used measures of the quality
      of pharmacotherapy for patients with schizophrenia and compared these measures
      across a sample of patients from the Department of Veterans Affairs (VA) and the
      private sector. METHODS: A random sample of all patients diagnosed with
      schizophrenia in the VA during fiscal year (FY) 2000 was identified using
      administrative data. In the private sector, a sample of patients diagnosed with
      schizophrenia in 2000 was identified using MEDSTAT's MarketScan database. For
      both groups, use of antipsychotic medications was studied and measures of the
      quality of pharmacotherapy were constructed, including whether patients were
      prescribed any antipsychotic medication, one of the newer atypical
      antipsychotics, and whether dosing adhered to established treatment
      recommendations. These measures were compared across the two groups using
      logistic regression models, controlling for age, gender, and comorbid diagnoses.
      RESULTS: Most patients with a diagnosis of schizophrenia (82% in the VA and 73%
      in the private sector) received an antipsychotic medication, usually one of the
      newer atypical drugs. Patients in the VA were more likely to be dosed above
      treatment recommendations, and less likely to be dosed below treatment
      recommendations. Overall, differences in proportion schizophrenia patients dosed
      according to recommendations were not statistically different across the two
      systems (60% in the VA, 58% in the private sector). CONCLUSIONS: Differences
      between the two systems were mixed, with the VA outperforming the private sector
      with respect to some measures and doing worse on others. IMPLICATIONS FOR HEALTH
      CARE PROVISION: Although the VA and the private sector were comparable with
      respect to the quality measures used in this study, there is room for improvement
      in both systems. Treatment recommendations are based on the best available
      clinical evidence of effectiveness and safety. Quality of care might be improved
      with better adherence to these recommendations. IMPLICATIONS FOR HEALTH POLICIES:
      Relatively low rates of adherence to treatment recommendations may be due to lack
      of awareness of these recommendations among prescribing physicians, or a belief
      that the recommendations are inadequate. To the extent that low rates of
      adherence to treatment recommendations are caused by a lack of awareness among
      physicians, policies should be developed to disseminate this information and
      encourage the appropriate use of these medications. IMPLICATIONS FOR FURTHER
      RESEARCH: Further research is needed to understand physician prescribing
      decisions for these medications. To the extent that physicians feel treatment
      recommendations for these drugs are inadequate, further research is needed to
      refine the recommendations.

PMID- 14646005
TI  - Estimating earnings losses due to mental illness: a quantile regression approach.
AB  - BACKGROUND: The ability of workers to remain productive and sustain earnings when
      afflicted with mental illness depends importantly on access to appropriate
      treatment and on flexibility and support from employers. In the United States
      there is substantial variation in access to health care and sick leave and other
      employment flexibilities across the earnings distribution. Consequently, a
      worker's ability to work and how much his/her earnings are impeded likely depend
      upon his/her position in the earnings distribution. Because of this, focusing on
      average earnings losses may provide insufficient information on the impact of
      mental illness in the labor market. AIMS: In this paper, we examine the effects
      of mental illness on earnings by recognizing that effects could vary across the
      distribution of earnings. METHODS: Using data from the National Comorbidity
      Survey, we employ a quantile regression estimator to identify the effects at key
      points in the earnings distribution. RESULTS: We find that earnings effects vary
      importantly across the distribution. While average effects are often not large,
      mental illness more commonly imposes earnings losses at the lower tail of the
      distribution, especially for women. In only one case do we find an illness to
      have negative effects across the distribution. IMPLICATIONS: Mental illness can
      have larger negative impacts on economic outcomes than previously estimated, even
      if those effects are not uniform. Consequently, researchers and policy makers
      alike should not be placated by findings that mean earnings effects are
      relatively small. Such estimates miss important features of how and where mental
      illness is associated with real economic losses for the ill.

PMID- 14646006
TI  - Budget and financing of mental health services: baseline information on 89
      countries from WHO's project atlas.
AB  - BACKGROUND: Very little information is available on budget and financing of
      mental health services in the world. AIMS OF THE STUDY: During year 2001, WHO
      collected information from all countries on resources available for mental health
      care as a part of Project Atlas. The present report seeks to describe the
      situation regarding federal budgets and financing of mental health care at the
      country level. It also examines the association between relative allocation of
      health budget to mental health and mental health policy, programme and resource
      indicators in 89 countries. METHOD: The information was collected through a
      questionnaire (with an accompanying glossary) that was sent to the mental health
      focal point in the Ministry of Health of each country. Eighty nine countries
      provided information on their mental health budget as a proportion of health
      budget. In addition, information was obtained on policy, programme and mental
      health resource indicators (beds, personnel, services to special population and
      availability of drugs). RESULTS: The results showed that 32% of 191 countries did
      not have a specified budget for mental health. Of the 89 countries that supplied
      the requisite information 36% spent less than 1% of their total health budget on
      mental health. Many countries from Africa (79%) and the South East Asia (63%)
      were in this subgroup. Comparison with the Global Burden of Disease data showed a
      marked disparity between burden and resources. Lower income countries allocated a
      lesser proportion of their health budget on mental health in comparison to higher
      income countries. The primary method of financing mental health care in most
      countries was tax-based (60.2%), but many low-income countries depended on out-of
      pocket expenditure (16.4%). The presence of mental health policies and programmes
      in general was not associated with the proportion of health budget allocated to
      mental health. Counties categorized based on the proportion of mental health
      budget to health budget, differed significantly in terms of policy on disability
      benefits and mental health resource indicators (beds, personnel, services for
      special populations and availability of drugs). DISCUSSION AND LIMITATIONS:
      Federal allocation for mental health care in most countries is low compared to
      the burden of these disorders. There is also a large disparity among countries
      and regions. Limitations of the study were, an exclusive reliance on government
      sources and the difficulty some governments faced in providing accurate
      information on federal mental health budget as it was not identified separately.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: To use resources more efficiently
      and judiciously, countries should support integration of services, reallocation
      of mental health beds, training in mental health to providers and services for
      special populations. IMPLICATIONS FOR HEALTH POLICIES: Most countries need to
      increase their mental health budgets in order to provide necessary services.
      Countries with out-of-pocket payment as the primary method of mental health
      financing should seek to establish social insurance mechanisms. IMPLICATIONS FOR
      FURTHER RESEARCH: More research needs to be conducted to gather specific
      information on mental health financing in relation to policy and service
      planning.

PMID- 14646007
TI  - Financing global mental health services and the role of WHO.
AB  - A concrete indicator of a government's commitment to mental health services is
      the amount of financial resources it allocates. To encourage the government to
      increase mental health funding, it would require additional research and
      dissemination findings on the economic consequences of mental health disorders,
      cost-effectiveness benefits of alternatives treatment, and alternative methods of
      financing for mental health illnesses. In addition, an organized consumer group
      can be an effective means in informing legislative and government policy makers.
      Public financing alone is not sufficient for treating mental illness. Private
      financing may supplement public funding. It would be important to combine both
      public and private funding to deliver adequate services for mental illness
      patients. WHO has been very effective in global tobacco control and SARS
      epidemic. The new administration should use this successful momentum to initiate
      a global funding campaign for mental health disorder as a top priority.

PMID- 14646008
TI  - From financial analysis to policy development in mental health care: the need for
      broader conceptual models and partnerships.
AB  - International mental health economics is emerging as a significant field in the
      increasingly intricate and interactive world in which we live. In line with this,
      the conceptualisation and gathering of pertinent data for international studies
      such as WHO's Atlas Project pose considerable methodological challenges. This
      paper outlines the need for broader conceptual models and partnerships and
      discusses some promising endeavours.

PMID- 14646009
TI  - Iodixanol density gradient preparation in university of wisconsin solution for
      porcine islet purification.
AB  - Generally, prior to the purification of isolated pancreatic islets, the
      collagenase-digested tissue is incubated in the University of Wisconsin solution
      (UWS; approximately 320 mOsm) for osmotic stabilization to preserve or improve
      the density differences between islets and acinar fragments. The adverse effects
      arising from the subsequent pelleting and resuspension of the islets in a second,
      different (often highly hyperosmotic) purification solution are avoided in the
      protocol described here; preparation of the purification medium is simply
      achieved by mixing the UWS preincubated islets with a second UWS containing the
      inert impermeant iodixanol. Flotation of the islets isolated from juvenile
      porcine pancreases through this mildly hypertonic (approximately 380 mOsm)
      gradient of iodixanol-UWS achieves a much higher recovery of islets of an
      improved viability than the customary method using a Ficoll gradient. The method
      has been extended to human islet purification.

PMID- 14646010
TI  - Quality of life philosophy: when life sparkles or can we make wisdom a science?

PMID- 14646011
TI  - Quality of life philosophy I. Quality of life, happiness, and meaning in life.
AB  - In the Danish Quality of Life Survey, we asked 10,000 people about their quality
      of life with the validated SEQOL questionnaire with more than 300 questions on
      their quality of life. How did they feel? How content were they with their lives?
      How happy were they? Did they feel their needs were fulfilled? And many more
      questions. We asked the questions we believed to be important for their quality
      of life (QOL). The results were quite surprising and forced us to recontemplate
      the following philosophical questions: What is quality of life, happiness, and
      meaning in life? What is a human being? Do we need a new biology? Is the brain
      the seat of consciousness? How do we seize the meaning of life and by doing so,
      will we become well again? What are the key concepts of quality of life? The
      meaning of life is connectedness and development. It is about realizing every
      opportunity and potential in one"s existence. The opportunities must be found and
      acknowledged. What do you find when you find yourself deep down? You find your
      real self and your purpose in life. You realize that you are already a part of a
      larger totality. Antonovsky called it "coherence". Maslow called it
      "transcendence". Frankl called it "meaning of life". We call it simply "being".
      To test if these philosophical questions are actually relevant for medicine, we
      looked at the consequences for patients being taught the quality of life
      philosophy. Quite surprisingly we learned from our pilot studies with "quality of
      life as medicine" that just by assimilating the basic concepts of the quality of
      life philosophy presented in this series of papers, patients felt better and saw
      their lives as more meaningful. The improvement of the patient"s personal
      philosophy of life seems to be the essence of holistic medicine, helping the
      patient to assume more responsibility for his or her own existence.

PMID- 14646012
TI  - Quality of life philosophy II: what is a human being?
AB  - The human being is a complex matter and many believe that just trying to
      understand life and what it means to be human is a futile undertaking. We believe
      that we have to try to understand life and get a grip on the many faces of life,
      because it can be of great value to us to learn to recognize the fundamental
      principles of how life is lived to the fullest. Learning to recognize the good
      and evil forces of life helps us to make use of the good ones. To be human is to
      balance between hundreds of extremes. Sometimes we have to avoid these extremes,
      but at other times it seems we should pursue them, to better understand life.
      With our roots in medicine, we believe in the importance of love for better
      health. The secret of the heart is when reason and feelings meet and we become
      whole. Where reason is balanced perfectly by feelings and where mind and body
      come together in perfect unity, a whole new quality emerges, a quality that is
      neither feeling nor reason, but something deeper and more complete. In this
      paper, we outline only enough biology to clarify what the fundamental inner
      conflicts are about. The insight into these conflicts gives us the key to a great
      deal of the problems of life. To imagine pleasures greater than sensual pleasures
      seems impossible to most people. What could such a joy possibly be? But somewhere
      deep in life exists the finest sweetness, the greatest quality in life, the pure
      joy of being alive that emerges when we are fully present and life is in balance.
      This deep joy of life is what we call experiencing the meaning of life.

PMID- 14646013
TI  - Quality of life philosophy III. Towards a new biology: understanding the
      biological connection between quality of life, disease, and healing.
AB  - This paper addresses (in a philosophical way) the complex and enigmatic interface
      between matter, life, and consciousness in modern medical science. The problem
      today in understanding living matter is not at the molecular level, but at the
      macro level where all molecular activities in the individual cell are
      coordinated, and especially at a higher level, where the activities of all the
      organism"s cells are coordinated. Although we understand very much of the body"s
      chemistry, we have only just started to get the gist of the tremendous
      organization of living matter. We are just beginning to acknowledge the enormous
      flow of information that is needed to make everything function in a healthy
      organism, including consciousness, where every cell does exactly what it has to
      do to make the organs function. A concept that seems to be able to bridge the
      scientifically very different domains of matter, life, and consciousness seems to
      be "biological information". If a cell is seen as a liquid crystal in which the
      cell"s molecules constantly connect in firm mutual relationships only to dissolve
      again and become fluid and free, whenever the cell needs it, the backbone of the
      cell seems to be the information that organizes the cell. For example, in cell
      motion a cell is able to crawl with the help of a skeleton of fibers that can be
      created guided by biological information, whenever the cell needs the solidity
      provided by the fibers. The moment it has finished crawling or intends to crawl
      in another direction, these fibers will dissolve again. The fibers are made of
      millions of molecules that connect in an arranged pattern, and they dissolve when
      these molecules again let go of each other. How the cell precisely regulates such
      processes is today a complete mystery. How cells cocreate consciousness is also
      an enigma. All we can do is describe the cell and the organisms arising from its
      cells as filled with energy and information as well as an unbeatable ability to
      organize itself way down to the molecular level, where apparently the cell is in
      control of almost every single molecule. Our understanding today of how the
      information is stored and how it flows through living matter is still very
      limited. The source of the qualities (the qualia) characterizing the human being
      as a whole--like joy, love, motivation, consciousness, free will, wisdom,
      intuitive competence--is still practically unknown and scientifically
      unexplained, more than 50 years after science has turned itself towards these
      fundamental problems. We believe that we need a radically new biology and
      medicine to give the scientific explanations of the structure, dynamics, and
      quality of life, and of its consciousness.

PMID- 14646014
TI  - Quality of life philosophy IV. The brain and consciousness.
AB  - In this article we look at the brain's structure and function from a
      philosophical perspective. Although the brain at micro-level, with its trillions
      of ultra-thin nerve fibers, is one of the most complicated structures in the
      known universe, you can still grasp its composition if you go up to the level of
      the cell. How this structure functions is not quite clear. You can understand its
      function at fiber level, because it is fairly simple, and you can understand it
      at cell level, but it is already vague. Roughly speaking, you can envision a
      single nerve cell as a tiny, independent computer whose behavior is dependent on
      continuous calculations of all input. At organ level, the function can be
      understood as an extremely complex pattern machine. Finally, the brain"s function
      can be understood at the cognitive level as what provides consciousness through
      its ability to keep order in our complicated reality. The superior function of
      the brain is to connect the real us, our higher self, to the surrounding world.
      The brain has been developed so that it can create all possible complex patterns.
      The connectivity seems to imply that the patterns of the human brain are 1000
      dimensional. It is our vision that these complicated patterns arise from basic
      patterns in the quantum matter of which everything is created. In our opinion,
      our consciousness" special utilization of a patterned aspect of nature is what
      lies behind inscrutable statements like "Man is created in God"s image". We
      suggest that these patterns in matter are the basic, creative force that
      influences all living organisms. Unfortunately, science has only just begun to
      understand these patterns. The Bible's description of the origin of man is two
      people eating from the Tree of Knowledge and as punishment they are expelled from
      the Garden of Eden. What does that mean? It means that, as conscious creatures,
      we no longer were an unproblematic, harmonious part of the world around us. The
      great question is why this consciousness about the world, provided by the brain,
      is not a gift that makes life better instead of getting us expelled from the
      Garden of Eden. We think that our real problem is the fact that we are still not
      in control of our consciousness. Instead of it serving us, we have become its
      slaves. If we come to understand brain and consciousness in order to solve this
      basic problem of our existence, we shall again be able to become a coherent part
      of the world, both as individuals and as a species. We share the vision that such
      an understanding of the problems of consciousness will make medical science
      holistic and will bring quality of life, health, and the ability to function to
      its patients.

PMID- 14646015
TI  - Quality of life philosophy V. Seizing the meaning of life and becoming well
      again.
AB  - This paper presents a positive philosophy of life developed to support and
      inspire patients to take more responsibility for their own lives and to draw more
      efficiently on their known or hidden resources. The idea is that everybody can
      become wiser, use themselves better, and thus improve quality of life, subjective
      health, and the ability to function. To be responsible means to see yourself as
      the cause of your own existence and state of being. To be the one who forms your
      own life to your liking, so that others do not shape it in the way they prefer to
      see you. Seen this way, taking responsibility in practice is one of the most
      difficult things to do. One of the greatest and most difficult things to do in
      this context is to be able to love. To be the one who loves, instead of being the
      one who demands love, care, awareness, respect, and acceptance from somebody
      else. Since almost all of us have had parents who maybe loved us too little and
      mostly conditionally, we all harbor a deep yearning to be loved as we are,
      unconditionally. A lot of our energy is spent trying to find recognition and
      acceptance, more or less as we did as children from our parents, who created the
      framework and defined the rules of the game. But today, reality is different. We
      have grown up and now life is about shaping our own existence. So we must be the
      ones who love. This is what responsibility is all about. Taking responsibility
      is, quite literally, moving the barriers in our lives inside ourselves. Taking
      responsibility for life means that you are willing to see that the real barriers
      are not all these external ones, but something that can be found within yourself.
      Of course there is an outside world that cannot be easily shaped according to
      your dreams. But a responsible point of view is that although it is difficult,
      the problem is not impossible; it is your real challenge and task. If there is
      something you really want, you can achieve it, but whether it happens depends on
      your wholehearted, goal-oriented, and continuous attempts. This paper describes
      the philosophy about seizing the meaning of life and becoming well again, even
      when there is little time left.

PMID- 14646016
TI  - Quality of life philosophy VI. The concepts.
AB  - The about a hundred central concepts related to research in the global quality of
      life can, in a holistic medical frame of interpretation, be organized under ten
      abstract key concepts: existence, creation of the world, state of being, daily
      living, talents, relations, sex, health, personal development, and therapy with
      subthemes as discussed in this paper. The paper shows that the concepts in each
      group can be seen as related to each other in a quite intuitive and logical way,
      to give a coherent quality of life philosophy that allows the physician to
      encourage, inspire, and support his patient. In every consultation, one new
      concept and idea of existence can be taught to the patient, helping him or her to
      realize the meaning of life, the source of joy, and the reason for the actual
      suffering. In this way, we help the patient to mobilize hidden and known
      resources and to improve quality of life, subjective health, and the ability to
      function. The concepts were harvested in 2003 at a Nordic seminar on quality of
      life research, held in Sweden. Life does not only cohere on the inside, but also
      on the outside. The same power that ties together all the cells in our body,
      seems to tie us together in relationships and new wholeness. This power evolves
      into new kinds of relations that unite on more and more complex levels, with the
      global ecosystem as the highest known level. Our intentions come from this
      coherent matrix of life. In the beginning of our life, the web of life itself
      gave birth to our fundamental purpose of life. The abstract purpose determines
      the frame of interpretation of reality: How we will perceive ourselves throughout
      life, our inner life, and the world around us. The frame of interpretation is
      pitched in language and concepts, in fact it creates our perceptions. Based on
      these perceptions and our purposes of life, our behavior arises. Our
      consciousness evolves through the witnessing of our behavior and through the
      response caused by it. Through the slowly acquired mastering of our surrounding
      world, we obtain our power, which gives us success in life, when we use it
      responsibly and unite it in harmony with our deepest purpose of life. When many
      people experience not having success, it is because they are not conscious about
      their original purpose or the deepest meaning of their lives. They do not know
      themselves. They do not experience the world in that way and do not realize that
      they themselves are the cause. Therefore responsibility and self-knowledge, which
      add up to wisdom, are the ways to a good and successful life.

PMID- 14646017
TI  - Holistic medicine III: the holistic process theory of healing.
AB  - It is possible to understand the process of healing from a holistic perspective.
      According to the life mission theory, we can stretch our existence and lower our
      quality of life when we are in crises, to survive and adapt, and we can relax to
      increase our quality of life when we later have resources for healing. The
      holistic process theory explains how this healing comes about: Healing happens in
      a state of consciousness exactly opposite to the state of crises. The patient
      enters the "holistic state of healing" when the (1) patient and (2) the physician
      have a perspective in accordance with life, (3) a safe environment, (4) personal
      resources, (5) the patient has the will to live, (6) the patient and (7) the
      physician have the intention of healing, (8) the trust of the patient in the
      physician, and (9) sufficient holding. The holding must be fivefold, giving the
      patient (1) acknowledgment, (2) awareness, (3) respect, (4) care, and (5)
      acceptance. The holistic process has three obligatory steps: (1) to feel, (2) to
      understand, and (3) to let go of negative decisions. This paper presents a theory
      for the holistic process of healing, and lists the necessities for holistic
      therapy restoring the quality of life, health, and ability to function of the
      patient.

PMID- 14646018
TI  - Oil production and groundwater quality in the Edwards-Trinity Plateau Aquifer,
      Texas.
AB  - Chloride concentrations and chloride/bromide ratios from 198 water wells in the
      Edwards-Trinity Plateau Aquifer were compiled, mapped, and evaluated within the
      context of regional geology and land use. The study area occupies eight counties
      in west-central Texas, within which oil production and agriculture are
      predominant land uses. Samples from 49 wells had chloride concentrations above
      the 250 mg/l secondary drinking water standard, 22 samples had greater than 500
      mg/l chloride, and 9 samples exceeded 1000 mg/l chloride. Of the 22 samples above
      500 mg/l chloride, 10 had relatively low chloride/bromide ratios of less than
      300, consistent with oilfield brine, and 2 had ratios above 2000, consistent with
      groundwater impacted by evaporite dissolution. The remaining ten samples had
      chloride/bromide ratios ranging from 300 to 2000, consistent with partial mixing
      of unimpaired groundwater with evaporite-laden water. There were no significant
      correlations between chloride concentration and well depth, inconsistent with
      contaminants originating at the land surface. Results of this study suggest that
      evaporite dissolution and oilfield brine locally impact the Edwards-Trinity
      Plateau Aquifer, but the problem is not regionally pervasive.

PMID- 14646019
TI  - Use of electrical vestibular stimulation to alter genioglossal muscle activity in
      awake cats.
AB  - Prior work has shown that the vestibular system contributes to regulating
      activity of upper airway muscles including the tongue protruder muscle
      genioglossus. The goal of the present experiments was to determine whether
      electrical vestibular stimulation could potentially be used to alter genioglossal
      activity in awake animals. Six adult cats were instrumented for recording of EMG
      activity from genioglossus, abdominal musculature, and triceps. In addition, a
      silver ball electrode was implanted on the round window for stimulation of
      vestibular afferents. Subsequently, stimulation and recordings were conducted
      while animals were awake. In all cases, stimulation using single shocks or trains
      of pulses > 100 microA in intensity produced responses in all muscles, including
      genioglossus. The latency of the genioglossal response was approximately 12 msec,
      and delivering continuous current trains to the labyrinth chronically elevated
      the muscle's activity. Although a number of muscles were affected by the
      stimulus, animals experienced no obvious distress or balance disturbances.
      Vestibular stimulation remained effective in producing genioglossal responses
      until experiments were discontinued 1-2 months following onset. These data
      suggest that electrical vestibular stimulation could potentially be used
      therapeutically to alter upper airway muscle activity.

PMID- 14646020
TI  - Bilateral peripheral vestibular lesions produce long-term changes in spatial
      learning in the rat.
AB  - In order to investigate whether bilateral peripheral vestibular lesions cause
      long-term impairment of spatial learning, rats were tested in a reference memory
      radial arm maze learning task at least 5 weeks following a bilateral
      labyrinthectomy (BL) or sham control lesion. All control rats reached criterion
      (i.e., 1 error or less, averaged across 7 trials for 3 consecutive days of
      training) but only 4 of the 8 BL rats had reached criterion by day 21 of the
      training sessions. The control rats reached criterion more quickly than the
      lesioned rats (Control, 7.0 +/- 0.63 days, Lesioned, 15.8 +/- 1.4 days, t10=
      5.84, p < 0.0001). This difference resulted from the greater number of errors
      made by the BL animals. However, the latency to respond was comparable as a
      result of the increased locomotor activity of the BL group (i.e., 'hyperkinesis),
      and the overall rate of acquisition of the task, as indicated by analysis of the
      exponential decrease in errors over the entire training period, was not
      significantly different between the 2 groups. The results of this study
      demonstrate that BL in rats produces long-term changes in performance in a
      spatial reference memory task, which are not simply due to the inability to move
      but may relate to the way that the brain uses vestibular information to create
      spatial representations and determines behavioural strategies on the basis of
      these representations.

PMID- 14646021
TI  - The interutricular distance determined from external landmarks.
AB  - Knowledge of the exact distance between the utricles is important in new
      vestibular tests, such as the unilateral centrifugation (UC) test for the
      unilateral examination of the utricles. During this test, subjects are rotated at
      constant velocity and simultaneously laterally displaced along an interaural axis
      so that one labyrinth becomes aligned with the axis of rotation. When the axis of
      rotation crosses precisely through one labyrinth, only the opposite labyrinth is
      stimulated. To achieve this setup, precise knowledge of the interutricular
      distance is needed. The purpose of this study is to investigate the correlation
      between the interutricular distance (IUD), measured on T2-weighted magnetic
      resonance images, and specific external measures of head dimensions such as
      distance nasion-inion, intermastoid distance (IMD), distances between the
      temporomandibular joints and between the lateral margins of the orbits. Data have
      been collected in a series of 50 subjects (25 men and 25 women). On MR images we
      found a mean IUD of 7.22 cm (SD = 0.42 cm). There was a strong correlation
      between the IUD measured on MR images and the intermastoid distance. A linear
      combination of the IMD, nasion-inion distance and height of the subjects could
      predict the IUD very satisfactory (R = 0.85, adjusted R2=0.723). We also
      determined a measure of eccentricity of the vestibular labyrinths. The 95%
      prediction interval for the asymmetry appeared to be less than 4.3%.

PMID- 14646022
TI  - Vestibulo-autonomic control in man: Short- and long-latency vestibular effects on
      cardiovascular function.
AB  - We examined the hypothesis that vestibular signals may exert a rapid control on
      the heart adjusting cardiovascular function to maintain homoestasis during
      changes in body posture. Short- and long-latency effects of vestibular
      stimulation on heart rate (HR), systolic blood pressure (SP), diastolic pressure
      (DP) and digital blood flow (BF) were studied in fourteen normal controls (NC)
      and nine labyrinthine-defective subjects (LDS) exposed to abrupt head
      accelerations. Subjects lay supine with their head suspended in a sling whose
      'release' was triggered at delays of 170 ms and 570 ms after an R-spike of the
      ECG. Release caused the head to fall with an acceleration approximately 0.8 g for
      approximately 140 ms. Three additional NC underwent head drops at 170 ms, 370 ms,
      470 ms and 570 ms to determine response latencies with precision. In NC, the
      short-latency response to head drops timed 170 to 470 ms after an R-spike was to
      shorten the time to the next R-spike in comparison to pre-drop heartbeat cycles.
      Drops at 570 ms delay shortened only the succeeding post-stimulus RR-interval. In
      LDS, head drops timed 170 ms after a heartbeat failed to shorten the ongoing
      cardiac cycle. For both delays only the succeeding cardiac cycle was
      significantly shortened. In all subjects, SP rose slightly by approximately 1-3%
      and BF decreased by 7-24% after 3-4 heartbeats post-drop. The results are
      evidence for an excitatory vestibulo-cardiac reflex in man which accelerates
      heart rate at a latency circa 500-600 ms. SP and BF are affected at longer
      latencies of several heart beats. A delayed increase of heart rate in response to
      postural challenge may contribute to the autonomic distress experienced by
      patients with vestibular loss.

PMID- 14646023
TI  - Effects of hypothermic anesthesia of the feet on vibration-induced body sway and
      adaptation.
AB  - The aim of this study was to investigate the significance of information from the
      plantar cutaneous mechanoreceptors in postural control and whether postural
      control could compensate for reduced cutaneous information by adaptation. Sixteen
      healthy subjects were tested with eyes open or eyes closed with hypothermic and
      normal feet temperature during posturography where body sway was induced by
      vibratory proprioceptive stimulation towards both calf muscles. The hypothermic
      anesthesia was obtained by cooling the subject's feet in ice water for 20
      minutes. Body movements were evaluated by analyzing the anteroposterior and
      lateral torques induced towards the supporting surface by a force platform during
      the posturography tests. The reduction of cutaneous sensor information from the
      mechanoreceptors of the feet significantly increased the vibration-induced torque
      variance mainly in the anteroposterior direction. However, the effects of
      disturbed mechanoreceptors information was rapidly compensated for through
      postural adaptation and torque variance was in level with that without anesthesia
      within 50 to 100 seconds of stimulation, both when standing with eyes open and
      eyes closed. Our findings suggest that somatosensory input from mechanoreceptors
      in the foot soles contribute significantly in maintaining postural control, but
      the sensory loss could be compensated for.

PMID- 14646024
TI  - Quantitative measurement of vertigo frequency: preliminary results.
AB  - Persons who experience vertigo often describe their symptoms as a sensation of
      oscillations. Based on such a description, a pilot study was performed to
      determine if the frequency of the vertigo sensation could be quantified in a
      manner analogous to tone matching in tinnitus treatment. Fifteen subjects were
      tested using a virtual image system that consisted of a head mounted display
      showing a scene that oscillated horizontally or vertically at an adjustable
      frequency. Subjects were asked to adjust the direction and frequency to match
      their typical vertigo sensation. Results show that most persons with chronic
      vertigo had symptoms that could be realistically simulated by vection induced by
      the oscillating scene and that matched to a consistent specific frequency. They
      reported an average frequency of 1.09 Hz (range 0.27 to 3.3 Hz, SD 0.25). The
      large majority (13 out of 15) matched to a horizontal stimulus. Subjects that
      gave particularly high subjective ratings of the similarity of the motion
      sensation (7-8 out of 10) from the vection to their vertigo had lower frequency
      matches (average 0.61 +/- 0.25). Repeated measurements in 4 subjects 8 to 27 days
      later showed consistent results. This vertigo measurement technique may be used
      in the future to assess the ability of vestibular rehabilitation to reduce
      chronic vertigo. Identification of a specific frequency of chronic vertigo may be
      important in the specification of rehabilitation exercises.

PMID- 14646025
TI  - Design of the Chicago Health and Aging Project (CHAP).
AB  - The design of the Chicago Health and Aging Project (CHAP) is described. CHAP is a
      longitudinal population study of common chronic health problems of older persons,
      especially of risk factors for incident Alzheimer's disease, in a biracial
      neighborhood of the south side of Chicago. Special attention is given to three
      unusual design features of the study. One feature is that clinical evaluation for
      Alzheimer's disease is confined to a stratified random sample of all
      participants. This feature results in substantial cost savings and substantially
      less bias than screening approaches but has the disadvantages of adding analytic
      complexity and requiring the use of indirect means to identify a disease-free
      cohort for the development of incident Alzheimer's disease. The second unusual
      feature is efficiently combining in analyses the successive independent multiple
      samples that are drawn, one from each data collection cycle. The third unusual
      feature is entering successive age cohorts of community residents into the study
      as they attain 65 years of age. This has the advantages of enhancing direct
      investigation of the effect of age on the action of risk factors for Alzheimer's
      disease and direct examination of cohort effects. The interaction of these
      features is described, especially as they pertain to a study in which data are
      collected in successive waves. The results from these waves must be combined for
      effective analysis of the relation among risk factors and incident disease.

PMID- 14646026
TI  - Multivariate modeling of two associated cognitive outcomes in a longitudinal
      study.
AB  - Longitudinal studies of Alzheimer's disease provide information about cognitive
      decline and predictors of this decline. However, overall cognitive function is
      comprised of many underlying processes, each of which may respond differently
      over time and may be affected by different predictors. In addition to studying
      how these processes decline independently, one might also be interested in how
      the processes decline together. Multivariate growth models, an extension and
      modification of random effects models, provide a means of dealing with these
      issues and enable assessing the association between the processes of interest.
      This technique allows for separate random effects and predictors for each process
      in the same model, thereby providing simultaneous estimates of the model
      parameters and variability for each process. We can then determine if factors
      associated with decline in one process are also associated with decline in
      another process and the extent to which the processes differ. We provide data
      that include information on two underlying processes of cognitive function,
      namely memory and executive function, to illustrate this methodology.

PMID- 14646027
TI  - Using a Rasch scale to characterize the clinical features of patients with a
      clinical diagnosis of uncertain, probable, or possible Alzheimer disease at
      intake.
AB  - OBJECTIVE: This study examined the clinical features of patients with clinical
      diagnoses of probable Alzheimer disease (AD), possible AD, and uncertain. DESIGN:
      Case study comparing three groups of AD patients diagnosed at their initial visit
      to an Alzheimer outpatient clinic. SETTING: Southern Illinois University School
      of Medicine's Center for Alzheimer Disease and Related Disorders (CADRD)
      assessment sites (20) in rural Illinois. PARTICIPANTS: 300 patients assessed at
      CADRD between January 1, 1994 and July 1, 2000. MEASUREMENTS: Patients were given
      an extensive clinical battery consisting of physical and neurologic examination,
      mental status testing including the Mini-Mental State Exam (MMSE), Short Blessed
      Dementia (SBD) and Blessed Dementia Scale (ADL), medical history evaluation, and
      laboratory tests. Other data included age at visit, gender, and medical history
      variables. RESULTS: Mean MMSE, SBD, and ADL scores differed significantly between
      groups (p's < 0.01). In all three cognitive tests, the uncertain group was the
      least impaired while the probable AD group was the most impaired. A Rasch model
      indicated that only the cognitive measures were useful in discriminating between
      the three diagnostic groups. CONCLUSION: In general, probable AD patients were
      distinguished from possible AD patients by the severity of their dementia as
      measured by the MMSE, ADL and SBD as well as Hachinski-Ischemic Score (HIS)
      scores. A Rasch model did well at predicting group membership based upon dementia
      measures only. The uncertain group differed from the AD groups in age and
      dementia severity as measured by the MMSE, ADL and SBD. Noting differences
      between this and previous studies, we speculate disparity may be related to
      differences in population ethnicity.

PMID- 14646028
TI  - Hypothesis testing of a change point during cognitive decline among Alzheimer's
      disease patients.
AB  - In this paper, we present a statistical hypothesis test for detecting a change
      point over the course of cognitive decline among Alzheimer's disease patients.
      The model under the null hypothesis assumes a constant rate of cognitive decline
      over time and the model under the alternative hypothesis is a general bilinear
      model with an unknown change point. When the change point is unknown, however,
      the null distribution of the test statistics is not analytically tractable and
      has to be simulated by parametric bootstrap. When the alternative hypothesis that
      a change point exists is accepted, we propose an estimate of its location based
      on the Akaike's Information Criterion. We applied our method to a data set from
      the Neuropsychological Database Initiative by implementing our hypothesis testing
      method to analyze Mini Mental Status Exam scores based on a random-slope and
      random-intercept model with a bilinear fixed effect. Our result shows that
      despite large amount of missing data, accelerated decline did occur for MMSE
      among AD patients. Our finding supports the clinical belief of the existence of a
      change point during cognitive decline among AD patients and suggests the use of
      change point models for the longitudinal modeling of cognitive decline in AD
      research.

PMID- 14646029
TI  - Apolipoprotein E and mortality in African-Americans and Yoruba.
AB  - The literature on the association between apolipoprotein E (ApoE) and mortality
      across ethnic and age groups has been inconsistent. No studies have looked at
      this association in developing countries. We used data from the Indianapolis
      Ibadan Dementia study to examine this association between APOE and mortality in
      354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria.
      Participants were followed up to 9.5 years for Indianapolis and 8.7 years for
      Ibadan. Subjects from both sites were divided into 2 groups based upon age at
      baseline. A Cox proportional hazards regression model adjusting for age at
      baseline, education, hypertension, smoking history and gender in addition to time
      dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was
      fit for each cohort and age group. Having ApoE epsilon4 alleles significantly
      increased mortality risk in Indianapolis subjects under age 75 (hazard ratio:
      2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis
      subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan
      subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or
      Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).

PMID- 14646030
TI  - Designing a Brief Alzheimer Screen (BAS).
AB  - CONTEXT: With advances in the treatment of Alzheimer's disease (AD), clinical
      focus has shifted to early patient identification. Memory recall tests and
      category fluency distinguish normal individuals from early AD patients.
      OBJECTIVE: Develop a brief test for general practitioners to screen for AD.
      Design. Examination of items from the MMSE and category fluency. SETTING AND
      PARTICIPANTS: A Brief Alzheimer Screen (BAS) was developed from cognitive
      assessments on 406 normal subjects and 342 mild AD patients in the CERAD
      (Consortium to Establish a Registry for AD) dataset. The derived measure was then
      applied to a second validation sample. MAIN OUTCOME MEASURE: Logistic regression
      was used to derive a predictive equation, which was then applied to two
      validation samples to estimate sensitivity and specificity. RESULTS: The
      resulting logistic model for discriminating between mild AD and controls
      included: recall of 3 words, number of animals named in 30 seconds, date, and
      spelling of WORLD backwards, (p < 0.001 for each) accounting for 77% of the
      variance. When applied to the validation samples, sensitivity and specificity
      were over 99% and 87%, respectively. CONCLUSIONS: These data support the use of
      the BAS as a potential screen of patients over 60 years of age.

PMID- 14646031
TI  - A latent variable model approach for assembling and scoring screening tests for
      dementia.
AB  - In dementia studies, the diagnosis of dementia often relies on results of
      screening tests aimed at measuring various dimensions of cognitive functions. The
      current practice of scoring a screening test involves simply summing the correct
      responses from each item. However, this method may be imprecise and inefficient
      in the predictive power of the score for dementia. We propose a latent variable
      model approach for the scoring and item selection of such tests. We model the
      item responses to be random variables based on latent variables. We also model
      the disease outcomes to be a function of the latent variables. Maximum likelihood
      estimates are obtained by maximizing the joint likelihood functions of disease
      and the item responses over a specified distribution function for the latent
      variables. Variances of model parameters are estimated using a nonparametric
      bootstrap method. We illustrate the approach using a screening test for dementia
      from a community-based study.

PMID- 14646032
TI  - Testing correlation of cognitive decline at adjacent stages of dementia.
AB  - This paper studies the correlation of cognitive progression for subjects whose
      dementia has made a transition from a milder stage of severity to the next stage
      of impairment. We model the progression of cognitive decline at adjacent stages
      of dementia by using a general linear mixed model. We also propose a three-step
      procedure to detect the best configuration of the covariance matrices for the
      random components in the model. After the best configuration of covariance
      matrices for the random components in the model is determined, we then recommend
      another two-step process to test whether there exists a significant correlation
      between the rate of cognitive decline before the transition, the cognitive status
      at the transition time, and the rate of cognitive decline after the transition.
      In addition, we present asymptotic confidence interval estimates for the
      correlations associated with a transition. This method is applied to several
      composite psychometric factor scores in the longitudinal database from the
      Alzheimer's Disease Research Center (ADRC) at Washington University in St. Louis.

PMID- 14646033
TI  - Anti-cardiolipin and anti-beta2-glycoprotein I (beta2GP-I) antibody assays as
      screening for anti-phospholipid syndrome.
AB  - BACKGROUND: Antiphospholipid antibodies are a family of autoantibodies that
      exhibit a broad range of target specificities and affinities, all recognizing
      various combinations of phospholipids, phospholipid binding proteins or both.
      OBJECTIVE: To evaluate the frequency of anticardiolipin (aCL) or anti-beta-2
      glycoprotein I (anti-beta2GPI) antibodies in a cohort of patients with primary
      (PAPS) and secondary (SAPS) antiphospholipid syndrome and other rheumatic and
      infectious conditions. METHODS: Sera were drawn from 226 patients with PAPS (n=
      66), SAPS (n= 60), rheumatoid arthritis (RA) (n= 30), scleroderma (SSc) (n= 30)
      or syphilis (n= 30). IgG, IgM, IgA aCL and anti-beta2GPI antibodies were
      determined for all patients. We employed Varelisa diagnostic kits (Pharmacia
      Diagnostics GmbH & Co.KG, Germany). RESULTS: In APS patients: aCL and anti
      betaGP1 antibodies were detected in 81.8% and 70% in PAPS and SAPS patients,
      respectively. In PAPS, aCL were detected in 71.2%, and anti-beta2GP1 in 50% of
      patients. In SAPS, aCL were detected in 63.3%, and anti-beta2GP1 in 53.3% of
      patients. In syphilis, aCL and anti-beta2GP1 antibodies were detected in 46.7% of
      patients in low levels: aCL in 36.7% and anti-beta2GP1 in 20% of patients. aCL
      antibodies were detected in 10%, 13.3%, and 0% of RA patients, SSc patients, and
      healthy persons, respectively. Anti-beta2GP1 antibodies were not detected in RA
      patients, SSc patients, and healthy persons. CONCLUSIONS: aCL and anti-beta2GP1
      antibodies are more frequently found in sera of APS patients, and can be found in
      low levels in syphilis. Anti-beta2GP1 assay found to be more specific than aCL in
      antiphospholipid antibodies determination.

PMID- 14646034
TI  - Anticardiolipin, other antiphospholipid antibody tests and diagnosis of the
      antiphospholipid syndrome.
AB  - The frequent occurrence of false positive results in the anticardiolipin (aCL)
      enzyme linked immunosorbent assay (ELISA) hampers its application in identifying
      the antiphospholipid syndrome (APS), a condition characterized by a myriad of
      clinical presentations. This study highlights some of the pitfalls in the use of
      assays for antiphospholipid (aPL) antibody in clinical practice. The aCL ELISA,
      commercially prepared anti-beta2-gylcoprotein 1 (beta2-GP1) and antiphospholipid
      (APhL) assays were evaluated in the diagnosis of antiphospholipid syndrome (APS)
      in 94 pregnant women who had spontaneous abortion and a group of 177 healthy
      blood donors. Serological tests were used to rule out syphilis as the cause of
      false positive results in the aCL ELISA. The prevalences of positive aCL ELISA
      results (29/94, 31% v 26/177, 14%; p = 0.001) and aCL antibodies of the IgM
      isotype (19/94, 20% v 6/177, 3%; $p = 0.001$) were significantly higher in
      aborters compared to healthy subjects. The majority of the sera which were
      positive in the aCL ELISA were shown to be false positives as 93% (27/29) of aCL
      positive aborters and 67% (8/24) of aCL positive healthy subjects were negative
      in the anti-beta2-GP1 assay. Similarly, the sensitivity of the APhL ELISA was low
      and only 1% (1/94) of the sera of aborters and 6% (11/177) of healthy subjects
      were positive in this assay. The frequent occurrence of anticardiolipin
      antibodies of the authentic non-autoimmune variety and the low sensitivity of the
      other more specific aPL assays make the positive aCL ELISA difficult to
      interpret. We recommend that the diagnosis APS be made with strict adherence to
      the preliminary criteria for classification of APS.

PMID- 14646035
TI  - Characterization of human hybridoma clones isolated from hemophilia patients with
      specificity for different domains of coagulating factor VIII.
AB  - Hemophilia A patients treated with human coagulating factor VIII (FVIII) may
      develop inhibitory antibodies (inhibitors). Characterization of the inhibitors at
      the clonal level may help exploring new therapeutic strategies. We have generated
      lymphoblastoid cell lines (LCLs) producing anti-FVIII antibodies from peripheral
      blood lymphocytes of hemophilia A patients with high inhibitor titers. We fused
      the anti-FVIII-positive LCLs with a heteromyeloma, to produce FVIII specific
      hybridomas. We determined the specificity, isotype, idiotypic and immunoglobulin
      (Ig) variable region heavy (VH) chain gene family profiles of the secreted
      antibodies (Ab) by ELISA, immunoblotting and RT-PCR. We established eight
      hybridomas which produced high titers of anti-FVIII Ab. All hybridomas secreted
      IgM Ab, associated with either kappa(5/8) or lambda(3/8) light chain. Analysis of
      the expressed VH genes by RT-PCR revealed that the hybridomas utilized only the
      VH1 (63%) or the VH3 (37%) gene families. Among the cross-reactive idiotypes
      (CRIs) we tested, only the VH1 and VK3b-associated CRIs were expressed by 3
      hybridomas. Immunoblotting of thrombin-digested FVIII demonstrated distinct
      patterns of reactivity of the monoclonal Ab (MAb) secreted by the hybridomas,
      which recognized either the A2 domain of the Fvm heavy chain, or the light chain,
      or both. Our findings suggest that: a) the isotype of the anti-FVIII Ab secreted
      by LCLs and hybridoma clones (IgM) differs from that of anti-FVIII Ab in vivo,
      which are predominantly IgG4: this suggests a negative selection of the isotype
      switched FVIII-specific B-cells in the periphery of these patients; b) the anti
      FVIII Ab have a biased representation of the VH1 gene family, and c) somatic
      mutations in the VH genes coding for FVIII specificity occur in the anti-FVIII Ab
      response, as evidenced by lack of expression of the VH-associated CRI.

PMID- 14646037
TI  - Development of hybridoma cells producing monoclonal antibody against human
      epsilon (epsilon) chain.
AB  - Epsilon (epsilon) chain is one of the five classes of immunoglobulins that plays
      an important role in allergic diseases. Production of monoclonal antibodies by a
      single clonotype against different epitopes of epsilon chain have high priority
      in development of diagnostic kits. In this study, an attempt was made to produce
      monoclonal antibodies against human epsilon chain. Balb/c mice were immunized
      with semipurified epsilon chain and spleen cells were fused with Sp2/0 mouse
      myeloma cell line in the presence of poly ethylene glycol. Supernatant of
      hybridoma cells were screened for detection of antibody by Enzyme-linked Immuno
      Sorbent Assay (ELISA) method. Cloning of selective high absorbance wells were
      done with limiting dilution method. The suitable clones (monoclones) were
      selected by ELISA and confirmed by immunoblot. The subclasses of the chosen
      monoclonal antibodies were determined and the clones freezed and kept in liquid
      nitrogen. During this study three successful fusions were carried out, which
      resulted in over than 100 clones with high production of anti- epsilon chain.
      Twelve clones with the highest titers were selected for cloning. After limiting
      dilution more than 50 monoclonal antibodies were produced and the unsuitable one
      (C1F2) displayed higher absorbance in reaction with purified IgE, relatively high
      cross-reactivity with IgM, and the highest cross-reactivity with IgG. In
      Immunoblotting, presence of relatively high-density band in reaction with IgE was
      confirmed. The unsuitable monoclonal antibody was shown to be IgG1 subclass with
      kappa light chain. It seems that, this monoclonal antibody could not be
      successfully useful in diagnostic kits.

PMID- 14646036
TI  - Generation of a human IgG3-streptavidin fusion protein. Implications for the
      inhibition and elimination of auto-reactive B cells.
AB  - Antibodies against self-molecules play a significant role in the development and
      progression of Systemic Lupus Erythematosus, as well as a number of other
      autoimmune disorders. Immunosuppressive drugs have been used to control this
      process. However, they are normally not specific to the offending cell, and can
      actually suppress beneficial immune responses to pathogens. In this paper a
      genetically engineered targeting molecule is described, which has the capacity to
      target antigen-specific B cells for inhibition or elimination. The targeting
      molecule is a fusion of streptavidin subunit to the constant region of human IgG3
      (IgG3-Av). It is demonstrated by ELISA and flow cytometry that IgG3-Av binds
      biotinylated antigen as well as human Fc gamma receptors present on myeloid
      cells. It is also shown by confocal microscopy and flow cytometry, that IgG3-Av
      can mediate Fc receptor-dependent phagocytosis of latex microspheres adsorbed
      with biotinylated antigen. Furthermore, the IgG3-Av construct can modulate Ca++
      flux, characteristic of B cell inhibition as well as ADCC of B cells in an
      antigen-specific manner. In summary, these studies describe an approach, which
      has the potential to be used as a treatment to inhibit or remove antigen-specific
      (auto-reactive) B cells.

PMID- 14646039
TI  - Assessment of cancer-associated biomarkers by positron emission tomography:
      advances and challenges.
AB  - Positron emission tomography (PET) provides a powerful means to non-invasively
      image and quantify protein expression and biochemical changes in living subjects
      at nano- and picomolar levels. As the field of molecular imaging develops, and as
      advances in the biochemistry, pharmacology, therapeutics, and molecular biology
      of disease are made, there is a corresponding increase in the number of
      clinically relevant, novel disease-associated biomarkers that are brought to the
      attention of those developing imaging probes for PET. In addition, due to the
      high specificity of the PET radiotracers being developed, there is a demand for
      PET cameras with higher sensitivity and resolution. This manuscript reviews
      advances over the past five years in clinical and pre-clinical PET
      instrumentation and in new PET probes and imaging methods associated with the
      latest trends in the molecular imaging of cancer. Included in the PET tracer
      review is a description of new radioligands for steroid receptors, growth factor
      receptors, receptor tyrosine kinases, sigma receptors, tumor-associated enzymes,
      gene reporter probes, markers for tumor hypoxia and metabolism, and sites
      associated with angiogenesis and cellular proliferation. The use of PET imaging
      in drug development, including the monitoring of cancer chemotherapy, also is
      discussed.

PMID- 14646040
TI  - Emerging ultrasound technologies for early markers of disease.
AB  - Ultrasound has been a popular clinical imaging modality for decades. It is well
      established as a means of displaying the macroscopic anatomy of soft-tissue
      structures. While conventional ultrasound methodologies (i.e., B-mode and Doppler
      methods) are well proven and continue to advance technically on a daily basis,
      e.g. by extending into higher frequencies and taking advantage of harmonic
      phenomena in tissues, fundamentally new ultrasound technologies also are emerging
      and offer exciting promise for making significant improvements in the clinical
      imaging of disease. These emerging methods include spectrum analysis, elasticity
      imaging, contrast-agent methods, and advanced flow detection and measurement
      techniques. Each provides independent information and, used alone, each can
      provide powerful new imaging capabilities; combined with each other, their
      capabilities may be even greater in many applications; and all in principle can
      be used in concert with other imaging modalities to offer the possibility of
      further improvements in disease detection, evaluation, and monitoring.

PMID- 14646041
TI  - Endoscopic microscopy.
AB  - In vivo endoscopic optical microscopy provides a tool to assess tissue
      architecture and morphology with contrast and resolution similar to that provided
      by standard histopathology--without need for physical tissue removal. In this
      article, we focus on optical imaging technologies that have the potential to
      dramatically improve the detection, prevention, and therapy of epithelial
      cancers. Epithelial pre-cancers and cancers are associated with a variety of
      morphologic, architectural, and molecular changes, which currently can be
      assessed only through invasive, painful biopsy. Optical imaging is ideally suited
      to detecting cancer-related alterations because it can detect biochemical and
      morphologic alterations with sub-cellular resolution throughout the entire
      epithelial thickness. Optical techniques can be implemented non-invasively, in
      real time, and at low cost to survey the tissue surface at risk. Our manuscript
      focuses primarily on modalities that currently are the most developed:
      reflectance confocal microscopy (RCM) and optical coherence tomography (OCT).
      However, recent advances in fluorescence-based endoscopic microscopy also are
      reviewed briefly. We discuss the basic principles of these emerging technologies
      and their current and potential applications in early cancer detection. We also
      present research activities focused on development of exogenous contrast agents
      that can enhance the morphological features important for cancer detection and
      that have the potential to allow vital molecular imaging of cancer-related
      biomarkers. In conclusion, we discuss future improvements to the technology
      needed to develop robust clinical devices.

PMID- 14646042
TI  - Intravital fluorescence facilitates measurement of multiple physiologic functions
      and gene expression in tumors of live animals.
AB  - The purpose of this report is to present an overview of the use of fluorescence
      imaging in vivo, with particular emphasis on oncology. It is important to note,
      however, that many of the methods described herein have been applied to the study
      of non-malignant tissues as well. Modern medicine and biology research has
      benefited greatly from an ever-expanding assortment of fluorescent markers and
      labels. These markers and labels have allowed investigators to observe the
      behavior and properties of cell and molecular entities of interest in the context
      of complicated biological systems such as a mammalian cell or a whole mouse.
      Methods developed to image fluorescence in whole mice have been valuable in
      studying patterns of tumor growth and metastases. Alternatively, more detailed
      information and a wide variety of endpoints can be obtained using "intravital"
      preparations. This review focuses on use of fluorescence imaging for intravital
      preparations. For detail on fluorescence imaging of whole animals, refer to
      reviews on this subject [1,2]. For oncologic applications, studies have focused
      primarily on window chamber preparations that allow for real-time visualization
      of tumor growth, vascularity, vascular responses to stimulation, vascular
      permeability, vascular orientation, flow instability, and the like. These
      endpoints have been used to show that there are functional differences between
      tumor and normal tissues with respect to these functions under baseline
      conditions and after therapeutic manipulation. Examples of some of these
      differences are provided in this review as a means to illustrate how they can be
      used.

PMID- 14646043
TI  - Near-infrared diffuse optical tomography.
AB  - Diffuse optical tomography (DOT) is emerging as a viable new biomedical imaging
      modality. Using near-infrared (NIR) light, this technique probes absorption as
      well as scattering properties of biological tissues. First commercial instruments
      are now available that allow users to obtain cross-sectional and volumetric views
      of various body parts. Currently, the main applications are brain, breast, limb,
      joint, and fluorescence/bioluminescence imaging. Although the spatial resolution
      is limited when compared with other imaging modalities, such as magnetic
      resonance imaging (MRI) or X-ray computerized tomography (CT), DOT provides
      access to a variety of physiological parameters that otherwise are not
      accessible, including sub-second imaging of hemodynamics and other fast-changing
      processes. Furthermore, DOT can be realized in compact, portable instrumentation
      that allows for bedside monitoring at relatively low cost. In this paper, we
      present an overview of current state-of-the -art technology, including hardware
      and image-reconstruction algorithms, and focus on applications in brain and joint
      imaging. In addition, we present recent results of work on optical tomographic
      imaging in small animals.

PMID- 14646044
TI  - Multi-resolution and wavelet representations for identifying signatures of
      disease.
AB  - Identifying physiological and anatomical signatures of disease in signals and
      images is one of the fundamental challenges in biomedical engineering. The
      challenge is most apparent given that such signatures must be identified in spite
      of tremendous inter and intra-subject variability and noise. Crucial for
      uncovering these signatures has been the development of methods that exploit
      general statistical properties of natural signals. The signal processing and
      applied mathematics communities have developed, in recent years, signal
      representations which take advantage of Gabor-type and wavelet-type functions
      that localize signal energy in a joint time-frequency and/or space-frequency
      domain. These techniques can be expressed as multi-resolution transformations, of
      which perhaps the best known is the wavelet transform. In this paper we review
      wavelets, and other related multi-resolution transforms, within the context of
      identifying signatures for disease. These transforms construct a general
      representation of signals which can be used in detection, diagnosis and treatment
      monitoring. We present several examples where these transforms are applied to
      biomedical signal and imaging processing. These include computer-aided diagnosis
      in mammography, real-time mosaicking of ophthalmic slit-lamp imagery,
      characterization of heart disease via ultrasound, predicting epileptic seizures
      and signature analysis of the electroencephalogram, and reconstruction of
      positron emission tomography data.

PMID- 14646045
TI  - Animal models for imaging.
AB  - Animal models can be used in the study of disease. This chapter discusses imaging
      animal models to elucidate the process of human disease. The mouse is used as the
      primary model. Though this choice simplifies many research choices, it
      necessitates compromises for in vivo imaging. In the future, we can expect
      improvements in both animal models and imaging techniques.

PMID- 14646046
TI  - Culture of chondrocytes in fibroin-hydrogel sponge.
AB  - Fibroin-hydrogel sponge and collagen gel were used as scaffold for in vitro
      cartilage regeneration. Fibroin-hydrogel sponge was formed by phase separation
      from freezed fibroin solution. Chondrocytes were harvested from proximal humerus,
      distal femur and proximal tibia of 4-week-old Japanese white rabbits and
      inoculated in the fibroin-hydrogel sponge and collagen gel. Those constructs were
      cultured in DMEM supplemented with 10% FCS and 50 ml L-ascorbate at 37 degrees C.
      Histological observation, measurement of sulfated glycosaminoglycan and cell
      density were carried out at 3, 7, and 14 days after the cultivation. Well-defined
      cartilage tissue can be seen both in the fibroin-hydrogel sponge and in the
      collagen gel. The matrix was intensely stained by safranin-O and showed a
      metachromatic reaction in both group. However, the quantity of sulfated
      glycosaminoglycan and cell density of the fibroin-hydrogel sponge group were
      increased more rapidly than these of the collagen gel group. Thus, the
      chondrocytes proliferated in the fibroin sponge without losing their
      differentiated phenotype. It is possible that culture environment in the fibroin
      sponge was suitable for chondrocytes regeneration.

PMID- 14646047
TI  - The water jet as a new tool for endoprosthesis revision surgery--an in vitro
      study on human bone and bone cement.
AB  - In revision surgeries of endoprostheses, the interface between implant and bone
      cement or bone must be loosened. Conventional tools have many disadvantages
      because of their size and limited range. Taking advantage of the selective and
      athermic cutting process, a plain water jet is already used in order to cut soft
      tissues. This study investigates the possibilities of both a plain and an
      abrasive water jet as cutting tools for revision surgery. Samples of the mid
      diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet
      (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30
      degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70
      MPa). For a PWJ a selective pressure range was identified, where only bone cement
      was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted
      in significantly higher cut depths in both materials. Material removal in bone
      was significantly less at the smaller jet-to-surface angle for both techniques.
      No clear selectivity between bone and bone cement was observed for application of
      the AWJ. However, the material removal rate was significantly higher for bone
      cement than for bone at all pressure levels. The results indicate that an AWJ
      might be an alternative tool for cement removal. The possibility for localised
      cutting at interfaces could be an advantage for revision of a non-cemented
      prosthesis.

PMID- 14646048
TI  - Investigations of the pushability behavior of cardiovascular angiographic
      catheters.
AB  - The placement of angiographic catheters into the vascular system is a routine
      procedure in modern clinical business. The definition of objective but not yet
      available evaluation protocols based on measurable physical quantities correlated
      to the empirical clinical findings is of utmost importance for catheter
      manufacturers for in-house product screening and optimization. In this context,
      we present an assessment of multiple mechanical and surface catheter properties
      such as static and kinetic friction, bending stiffness, microscopic surface
      topology, surface roughness, surface free energy and their interrelation.
      Theoretical framework, description of experimental methods and extensive data
      measured on several different catheters are provided and in conclusion a testing
      procedure is defined. Although this procedure is based on the measurement of
      several physical quantities it can be easily implemented by commercial
      laboratories testing catheters as it is based on relatively low-cost standard
      methods.

PMID- 14646049
TI  - Evaluation of dynamic visco-elastic properties during cartilage regenerating
      process in vitro.
AB  - The dynamic visco-elastic properties of regenerated cartilage tissue were
      measured to evaluate its mechanical function during cultivation. Harvested
      chondrocytes from 4-week-old Japanese white rabbits were inoculated into fibroin
      sponge at a cell concentration of about 5 x 10(7) cells/ml. Dynamic visco
      elasticity measurements were performed under compressive loading to evaluate the
      load bearing function of the articular cartilage. The dynamic modulus and the
      dynamic loss of the regenerated cartilage increased and the peak value of
      tandelta, as well as the frequency at the peak, decreased with increasing
      cultivation time. The pores of the fibroin sponge became filled with newly formed
      tissue as cultivation time increased. These changes in the visco-elastic
      properties of the regenerated cartilage were compared with those of a model
      system, ethylene propylene diene monomer sponge with interstitial fluid, and
      appear to be a result of increased fluid flow resistance and internal loss. We
      conclude that the changes in the dynamic visco-elastic properties of the
      regenerated cartilage were caused because of narrowing of the fluid path by
      synthesized extracellular matrix.

PMID- 14646050
TI  - Deterioration in the superelasticity of Ti sputter coated on NiTi orthodontic
      wire.
AB  - To evaluate the deterioration in the superelasticity of Ti-coated NiTi
      orthodontic wires, titanium was coated onto wires to form a 1-microm thick film
      using radio frequency magnetron sputtering. In superelasticity cycle tests, the
      sigma5.0 value (the stress at 5.0% strain) of a Ti-coated wire was lower than
      that of a non-coated wire by 6.2% after one cycle, and by 10.4% after 20 cycles.
      In a three point bend tests, the L2.0 value (the load at 2.0 mm deflection) of a
      Ti-coated wire was 2.55 N, and this was reduced by 39.0% of the L2.0 value of a
      non-coated wire (4.18 N). After the non-coated and the Ti-coated wires had been
      immersed in physiological saline for periods of four and eight weeks, the
      concentration of Ni ions released into each solution was detected using MIP-Mass,
      and Ni peak intensity of the wires was measured using XPS. After eight weeks, the
      concentration of Ni ions released from the non-coated and the Ti-coated wires was
      657 and 135 ppb, respectively. In a clinical test, no inflammation was observed
      during the entire attached period of four weeks in both the non-coated and the Ti
      coated wire. In the Ti-coated wire, little exfoliation of the Ti-coating was
      observed using SEM and EDS. It was concluded that Ti-coated NiTi orthodontic wire
      has much potential for its application, with a low probability of causing any Ni
      allergy.

PMID- 14646051
TI  - Automatic quantitative analysis of ore content of human tooth enamel based on
      image processing.
AB  - Introducing the theory of fuzzy set, mathematical morphology and computerized
      mask fast scanning, we developed the TOOTH.SCA software and method to analyze the
      effect of fluoride (NaF) on ore content of human tooth enamel automatically and
      quantitatively. And we obtained some characteristic parameters, such as the
      depth, the type and the demineralized content of every scathing layer of dental
      caries. The smallest scale of mask scanning is 0.1 microm x 0.1 microm and the
      time required to analyze a sample is only 12 s. The applied software and method
      we built play an important role to the research on the mechanism of pathological
      changes of teeth and preventing dental caries.

PMID- 14646052
TI  - Nonlinear and viscoelastic characteristics of skin under compression: experiment
      and analysis.
AB  - In physiological loading conditions, the soft tissues in the hands and fingers
      are predominantly in compression. The goal of the present study was to
      characterize the nonlinear and time-dependent behavior of skin in compression.
      The pigskin samples used in the study were collected from five different animals.
      The compression tests were performed in confined and unconfined loading
      configurations and at four different loading speeds (0.5, 1.0, 40, and 400
      microm/s). A multi-axial material model was proposed to simulate the nonlinear
      and viscoelastic behavior of the skin in compression. The good agreement between
      the model predictions and experimental data suggests that the mechanical behavior
      of the skin in compression can be well characterized using the Ogden strain
      energy potential combined with a time-integration using a Prony series. Our
      results show that the stress/strain curve of the skin is much stiffer in confined
      compression compared to that in unconfined compression, indicating that the
      compressibility of the skin is small.

PMID- 14646053
TI  - Investigation on Tc tuned nano particles of magnetic oxides for hyperthermia
      applications.
AB  - Superparamagnetic as well as fine ferrimagnetic particles such as Fe3O4, have
      been extensively used in magnetic field induced localized hyperthermia for the
      treatment of cancer. The magnetic materials with Curie temperature (Tc) between
      42 and 50 degrees C, with sufficient biocompatibility are the best candidates for
      effective treatment such that during therapy it acts as in vivo temperature
      control switch and thus over heating could be avoided. Ultrafine particles of
      substituted ferrite Co(1-a)Zn(a)Fe2O4 and substituted yttrium-iron garnet Y3Fe(5
      x)Al(x)O12 have been prepared through microwave refluxing and citrate-gel route
      respectively. Single-phase compounds were obtained with particle size below 100
      nm. In order to make these magnetic nano particles biocompatible, we have
      attempted to coat these above said composition by alumina. The coating of alumina
      was done by hydrolysis method. The coating of hydrous aluminium oxide has been
      done over the magnetic particles by aging the preformed solid particles in the
      solution of aluminium sulfate and formamide at elevated temperatures. In vitro
      study is carried out to verify the innocuousness of coated materials towards
      cells. In vitro biocompatibility study has been carried out by cell culture
      method for a period of three days using human WBC cell lines. Study of cell
      counts and SEM images indicates the cells viability/growth. The in vitro
      experiments show that the coated materials are biocompatible.

PMID- 14646054
TI  - Injectable polydimethylsiloxane-hydroxyapatite composite cement.
AB  - An injectable polydimethylsiloxane/hydroxyapatite (PDMS/HAp) composite cement was
      synthesised using linear PDMS and HAp (particles of about 100 nm in size) of
      different mass fractions. The effect of HAp mass fraction (5-60 mass%) on the
      hardness of PDMS/HAp composite cement was investigated. The hardness achieved is
      25-49 degrees ShA. Differential scanning calorimetry (DSC) was used to study the
      cross-linking process and the influence of HAp on the temperature and duration of
      PDMS/HAp cross-linking. The microstructure of composite cement surfaces after 10
      days in vivo tests was observed by scanning electron microscopy (SEM). The
      presence of well-adhered macrophages, fibroblasts and monocytes was found on the
      implant surface upon its extraction from the organism.

PMID- 14646055
TI  - The report of the cartilage regeneration using total joint regeneration system
      (internal-fixator type).
AB  - A new therapeutic system called the "total joint regeneration system" is proposed
      as a treatment for osteoarthritis and rheumatoid arthritis. We have developed
      devices which allow the regeneration of damaged cartilage under noninvasive
      mechanical stimulation. This paper introduces the basic concepts of total joint
      regeneration and reports the results of the first animal experiment using an
      internal-fixator device using rabbits and a dog.

PMID- 14646056
TI  - Evaluation of the effects of implant materials and designs on thermal necrosis of
      bone in cemented hip arthroplasty.
AB  - The exothermic polymerization of bone cement may induce thermal necrosis of bone
      in cemented hip arthroplasty. A finite element formulation was developed to
      predict the evolution of the temperature with time in the cemented hip
      replacement system. The developed method is capable of taking into account both
      the chemical reaction that generates heat during bone cement polymerization
      (through a kinetic model) and the physical process of heat conduction (with an
      energy balance equation). The possibility of thermal necrosis of bone was then
      evaluated based on the temperature history in the bone and an appropriate damage
      criterion. Specifically, we evaluate the role of implant materials and designs on
      the thermal response of the system. Results indicated that the peak temperature
      at the bone/cement interface with a metal prosthesis was lower than that with a
      polymer or a composite prosthesis in hip replacement systems. Necrosis of bone
      was predicted to occur with a polymer or a composite prosthesis while no necrosis
      was predicted with a metal prosthesis in the simulated conditions. When
      reinforcing osteoporotic hips with injected bone cement in the cancellous core of
      the femur, the volume of bone cement implanted is increased which may increase
      the risk of thermal necrosis of bone. We evaluate whether this risk can be
      decreased through the use of an insulator to contain the bone cement. No thermal
      necrosis of bone was predicted with a 3 mm thick polyurethane insulator while
      more damage is predicted for the use of bone cement without the insulator. This
      method provides a numerical tool for the quantitative simulation of the thermal
      behavior of bone-cement-prosthesis designs and for examining and refining new
      designs computationally.

PMID- 14646057
TI  - The lubricative function of artificial joint material surfaces by confocal laser
      scanning microscopy. Comparison with natural synovial joint surface.
AB  - The purpose of this study was to observe and compare the effect of the behavior
      of different lubricating surfaces, including articular cartilage and several
      artificial joint materials, under the physiological loading by confocal laser
      scanning microscopy (CLSM) to clarify the mechanism of lubrication in natural
      joints and subsequently improve the quality of artificial joints. In our
      experiment, even with considerable loading, natural articular cartilage exhibited
      a synovial fluid area and an area of direct and solid contact. In the region
      between these two areas, a liquid crystal layer was observed. On the other hand,
      the materials used for artificial joints (metal and polyethylene, which are now
      in use, and polyvinyl alcohol-hydrogel polymer which is being developed), did not
      exhibit neither a clear fluid pool area nor the intermediary area with liquid
      crystal formation. These results suggest that natural articular cartilage surface
      has a particular characteristic which builds up a synovial pooling area and
      liquid crystal formation in the third area by interaction with macromolecules in
      synovial fluid under the loading condition. These characteristics give natural
      articular cartilage its excellent lubricative function. To improve the quality of
      artificial joints, the characteristics of the implant material surface and the
      synovial macromolecules must be considered.

PMID- 14646058
TI  - Optimization of the geometry of total knee implant in the sagittal plane using
      FEA.
AB  - The aim of this research was to investigate the optimization of the geometry of
      an UHMWPE type of knee implant in the sagittal plane with minimum amount of wear.
      Finite element analysis has been used to analyze our proposed 780 models
      consisting of different design parameters. Maximum stress occurring in the whole
      tibial component, on the surface or subsurface of the plate, was considered as a
      design parameter to evaluate the wear condition. By avoiding the small contact
      area and high stresses in the tibial part, the maximum safe flexion angles have
      been determined. Other effective design factors such as implant stability, roll
      back distance, patella lever arm, and minimum bone resection have also been
      considered. Taking into account the variable parameters in the geometry of the
      implant parts, all possible models for the femoral component, which is made from
      metal, and the tibial component, which is made from UHMWPE, have been built in
      ANSYS and analyzed in the sagittal plane. By considering the effective mechanisms
      of wear in polyethylene, the results of the analyses were used to find the
      optimized geometry of a knee implant. This is the model, which is expected to
      experience the minimum wear, besides having some other properties of an ideal
      knee prosthesis.

PMID- 14646059
TI  - Bone bonding strength of sputtered hydroxyapatite films subjected to a low
      temperature hydrothermal treatment.
AB  - Hydroxyapatite (HA) was coated onto titanium substrates using radio frequency
      sputtering, and the coated HA films were crystallized in an autoclave at 110
      degrees C using a low temperature hydrothermal method. The crystallite size, the
      Ca/P ratio, and the surface of the films were observed using XRD, EDS, and SEM,
      respectively. An immersion test was carried out in physiological saline solution,
      and the film-to-substrate adhesion strength was measured using a pull-out test.
      From the XRD patterns, a sputtered film subjected to the hydrothermal treatment
      had crystallized after 24 h, and the crystallite size increased from 38.0+/-8.7
      to 81.4+/-19.1 nm. In immersion tests, an as-sputtered film completely dissolved
      after 1 d, whereas a sputtered film subjected to the hydrothermal treatment
      survived to 18.7+/-5.8% of the initial film thickness after four weeks. In pull
      out tests, the adhesion strength of the sputtered film to the substrate increased
      from 1.9+/-0.2 to 5.3+/-1.6 MPa after the hydrothermal treatment. A sputtered
      film subjected to the hydrothermal treatment and a plasma-sprayed coating on
      titanium columns were implanted in the diaphysis of the femora of six adult dogs,
      and a pull-out test was carried out after two, four, and 12 weeks. The sputtered
      film showed higher bone bonding strength than the plasma-sprayed coating at any
      period.

PMID- 14646061
TI  - Structural analyses of Phycodnaviridae and Iridoviridae.
AB  - The Phycodnaviridae, Iridoviridae and related viruses, with diameters of 1500
      2000 A, are formed from large trigonal arrays of hexagonally close-packed
      capsomers forming the faces of icosahedra [Yan et al. (2000), Nature Struct.
      Biol. 7, 101-103; Nandhagopal et al. (2002), Proc. Natl Acad. Sci. USA, 99, 14758
      14763]. Caspar and Klug predicted that such structures could be assembled from
      hexameric capsomers [Caspar & Klug (1962), Cold Spring Harbor. Symp. Quant. Biol.
      27, 1-24], as was subsequently found in numerous icosahedral viruses. During the
      course of evolution, some viruses, including the virus families mentioned above,
      replaced hexameric capsomers with pseudo-hexameric trimers by gene duplication.
      In large dsDNA icosahedral viruses, the capsomers are organized into
      'pentasymmetrons' and 'trisymmetrons'. The interactions between the trimeric
      capsomers can be divided into three groups, one between similarly oriented
      trimers and two between oppositely oriented trimers (trimers related by an
      approximately sixfold rotation). The interactions within a trisymmetron belong to
      the first class, whereas those between trisymmetrons and within the
      pentasymmetron are of the other two types. Knowledge of these distances permits a
      more accurate fitting of the atomic structure of the capsomer into the cryo
      electron microscopy (cryoEM) reconstruction of the whole virus. The adoption of
      pseudo-hexagonal capsomers places these viruses into a subset of the Caspar and
      Klug surface lattices.

PMID- 14646062
TI  - Crystallization and preliminary analysis of a dsDNA bacteriophage capsid
      intermediate: Prohead II of HK97.
AB  - HK97 Prohead II is an early intermediate in the maturation of HK97, a T = 7 dsDNA
      tailed bacteriophage related to bacteriophage lambda. Previously, selected capsid
      protein genes of HK97 were expressed in Escherichia coli and spontaneously
      assembled to form an icosahedral capsid that followed a maturation pathway
      closely similar to the authentic virion. The crystal structure of the mature HK97
      capsid (Head II) made in this way was reported at 3.5 A resolution. Additional
      high-resolution structures of intermediates are needed to understand the
      maturation mechanism. The crystal structure of expressed Prohead II will
      elucidate the early steps of HK97 assembly. Crystals of the Prohead II mutant
      W336F were grown in 0.1 M HEPES pH 7.5, 0.2 M CaCl(2) and 2-3% PEG 4000 at a
      Prohead II concentration of 16.5 mg ml(-1). It was not possible to grow high
      quality crystals of wild-type Prohead II. Diffraction was observed to 5 A
      resolution from these crystals on beamline 14BM-C at the Advanced Photon Source
      and data were collected to 5.5 A with a completeness of 77%. The space group was
      P2(1)3, with unit-cell parameter a = 707.0 A and four particles in the unit cell.
      The particles are on the body diagonals of the cubic cell, with icosahedral
      threefold axes coincident with crystallographic threefold axes. Self-rotation
      function and locked-rotation function analysis determined the particle
      orientation and a one-dimensional R-factor search along the body diagonal
      indicated that the particle centers were close to (1/4, 1/4, 1/4) and symmetry
      related positions. Molecular-replacement averaging and phase extension are under
      way.

PMID- 14646063
TI  - Structure of the hybrid cluster protein (HCP) from Desulfovibrio desulfuricans
      ATCC 27774 containing molecules in the oxidized and reduced states.
AB  - The hybrid cluster protein (HCP) from the sulfate-reducing bacteria Desulfovibrio
      desulfuricans ATCC 27774 has been isolated and crystallized anaerobically. The
      protein sample used in the crystallization studies was several months old, having
      been stored at 193 K, and initial crystal structure studies were unable to fully
      resolve details of the hybrid cluster despite the use of high-resolution data to
      1.25 A collected at the ESRF, Grenoble, France. Full elucidation of the structure
      has only become possible with the complete knowledge of the as-isolated and fully
      reduced crystal structures. The analysis clarifies the significant movements in
      the position of the Fe atom linked to the persulfide moiety in the oxidized as
      isolated protein and the S atom of the persulfide itself as the protein is
      reduced. The structures of the as-isolated and reduced states are discussed in
      terms of the putative function of the HCP proteins.

PMID- 14646064
TI  - Unravelling the structural chemistry of the colouration mechanism in lobster
      shell.
AB  - Biochemistry, biological crystallography, spectroscopy, solution X-ray scattering
      and microscopy have been applied to study the molecular basis of the colouration
      in lobster shell. This article presents a review of progress concentrating on
      recent results but set in the context of more than 50 years of work. The blue
      colouration of the carapace of the lobster Homarus gammarus is provided by a
      multimolecular carotenoprotein, alpha-crustacyanin. The complex is a 16-mer of
      five different subunits each binding the carotenoid, astaxanthin (AXT). A
      breakthrough in the structural studies came from the determination of the
      structure of beta-crustacyanin (protein subunits A1 with A3 with two shared bound
      astaxanthins). This was solved by molecular replacement using apocrustacyanin A1
      as the search motif. A molecular movie has now been calculated by linear
      interpolation based on these two 'end-point' protein structures, i.e.
      apocrustacyanin A1 and A1 associated with the two astaxanthins in beta
      crustacyanin, and is presented with this paper. This movie highlights the
      structural changes forced upon the carotenoid on complexation. In contrast, the
      protein-binding site remains relatively unchanged in the binding region, but
      there is a large conformational change occurring in a more remote surface-loop
      region. It is suggested here that this loop could be important in complexation of
      AXT and contributes to the spectral properties. Also presented here is the first
      observation of single-crystal diffraction of the full 'alpha-crustacyanin'
      complex comprising 16 protein subunits and 16 bound AXT molecules (i.e eight beta
      crustacyanins) at 5 A resolution. Optimization of crystallization conditions is
      still necessary as these patterns show multiple crystallite character, however,
      10 A resolution single-crystal diffraction has now been achieved. Provision of
      the new SRS MPW 10 and SRS MPW 14 beamline robotic systems will greatly assist in
      the surveying of the many alpha-crustacyanin crystallization trials that are
      being made. New solution X-ray scattering (SXS) measurements of beta- and alpha
      crustacyanin are also presented. The beta-crustacyanin SXS data serve to show how
      the holo complex fits the SXS curve, whereas the apocrustacyanin A1 homodimer
      from the crystal data naturally does not. Reconstructions of alpha-crustacyanin
      were accomplished from its scattering-profile shape. The most plausible
      ultrastructure, based on a fourfold symmetry constraint, was found to be a stool
      with four legs. The latter is compared with published electron micrographs. A
      detailed crystal structure of alpha-crustacyanin is now sought in order to relate
      the full 150 nm bathochromic shift of AXT to that complete molecular structure,
      compared with the 100 nm achieved by the beta-crustacyanin protein dimer alone.
      Rare lobster colourations have been brought to attention as a result of this work
      and are discussed in an appendix.

PMID- 14646065
TI  - Direct phasing at low resolution of a protein copurified with human paraoxonase
      (PON1).
AB  - In this paper, the low-resolution structure of a previously unknown protein
      copurified with human paraoxonase (PON1) is reported. The structure of this
      protein was very difficult to solve using classical crystallographic methods.
      Progress was made using a new phasing method based on topological analysis. From
      the experimental point of view, this method has the advantage of requiring only a
      simple low-resolution X-ray data set. The program used and the different steps of
      the data-processing and phasing procedure are described. The results provided an
      insight into the failure of previous molecular-replacement attempts. The low
      resolution shape of the protein which was presented with confidence is compared
      with and confirmed by the structure at 1.8 A solved subsequently using classical
      methods. This work shows that this direct-phasing method could be used
      systematically in difficult cases: it provides low-resolution structural
      information comparable with that obtainable by electron microscopy.

PMID- 14646066
TI  - Resolving the space-group ambiguity of crystals of tomato fruit
      polygalacturonase.
AB  - The first polygalacturonase from a plant, tomato fruit PG2, has been crystallized
      and data have been collected to a resolution of 1.87 A. The autoindexing program
      strongly favors one of the primitive orthorhombic cells. A plausible molecular
      replacement solution for two molecules in the asymmetric unit has been found for
      data assigned to space group P2(1)2(1)2(1). Although the numerical criteria and
      the electron-density maps are reasonable for this solution, manually adjusted
      models do not refine to an R factor below 0.48. Visual inspection of hkl Bragg
      planes does not reveal a breakdown in mm symmetry. Nevertheless, the correct
      space group has been determined to be P2(1), with similar unit-cell parameters, a
      beta angle of 90.04 degrees and four molecules in the asymmetric unit. The R(sym)
      of 0.053 for data processed in P2(1)2(1)2(1) is very similar to the R(sym) of
      0.047 for the same data processed in P2(1). Comparisons of the intermediate
      results using the P2(1)2(1)2(1) and P2(1) data sets are provided and the subtle
      indications of an initial erroneous space-group assignment are discussed.

PMID- 14646067
TI  - Reintroducing electrostatics into protein X-ray structure refinement: bulk
      solvent treated as a dielectric continuum.
AB  - Structural refinement of proteins involves the minimization of a target function
      that combines X-ray data with a set of restraints enforcing stereochemistry and
      packing. Electrostatic interactions are not ordinarily included in the target
      function, partly because they cannot be calculated reliably without a description
      of dielectric screening by solvent in the crystal. With the recent development of
      accurate implicit solvent models to describe this screening, the question arises
      as to whether a more detailed target function including electrostatic and
      solvation terms can yield more accurate structures or somewhat different
      structures of equivalent accuracy. The Generalized Born (GB) model is one such
      model that describes the solvent as a dielectric continuum, taking into account
      its heterogeneous distribution within the crystal. It is used here for X-ray
      refinements of three protein structures with experimental diffraction data to
      2.4, 2.9 and 3.2 A, respectively. In each case, a higher resolution structure is
      available for comparison. The new target function includes stereochemical
      restraints, van der Waals, Coulomb and solvation interactions, along with the
      usual X-ray pseudo-energy term, which employs the likelihood estimator of Pannu
      and Read. Multiple simulated-annealing refinements were performed in torsion
      angle space with a conventional target function and the new GB target function,
      yielding ensembles of refined structures. The new target function yields
      structures of similar accuracy, as measured by the free R factor, map/model
      correlations and deviations from the high-resolution structures. About 10% of
      side-chain conformations differ between the two sets of refinements, in the sense
      that the two ensembles of conformations do not completely overlap. Over 75% of
      the differences correspond to surface side chains. For one of the proteins, the
      GB set has a greater dispersion, indicating that for this case the conventional
      target function overestimates the true precision. As GB parameterization
      continues to improve, we expect that this approach will become increasingly
      useful.

PMID- 14646068
TI  - Distance distributions and electron-density characteristics of protein models.
AB  - The analytical expression for the distribution of an interatomic distance
      resulting from a known error-free distance and a Gaussian perturbation of the
      atomic coordinates is presented. This is used to estimate the coordinate error on
      the basis of known geometric features of protein models via the nearest-neighbour
      or the radial distance distribution. A simple relation is presented that
      describes the dependence of the map correlation on the positional error of the
      protein model, the resolution of the X-ray data and the overall atomic
      displacement parameter. The distribution of geometrical features and the relation
      between the map correlation and the positional error can be used in assisting the
      decision-making process during automated model-building procedures.

PMID- 14646069
TI  - Fisher's information in maximum-likelihood macromolecular crystallographic
      refinement.
AB  - Fisher's information is a statistical quantity related to maximum-likelihood
      theory. It is a matrix defined as the expected value of the squared gradient of
      minus the log-likelihood function. This matrix is positive semidefinite for any
      parameter value. Fisher's information is used in the quasi-Newton scoring method
      of minimization to calculate the shift vectors of model parameters. If the matrix
      is non-singular, the scoring-minimization step is always downhill. In this
      article, it is shown how the scoring method can be applied to macromolecular
      crystallographic refinement. It is also shown how the computational costs
      involved in calculation of the Fisher's matrix can be efficiently reduced. Speed
      is achieved by assuming a continuous distribution of reciprocal-lattice points.
      Matrix elements calculated with this method agree very well with those calculated
      analytically. The scoring algorithm has been implemented in the program REFMAC5
      of the CCP4 suite. The Fisher's matrix is used in its sparse approximation. Tests
      indicate that the algorithm performs satisfactorily.

PMID- 14646070
TI  - Structure of viscotoxin A3: disulfide location from weak SAD data.
AB  - The crystal structure of viscotoxin A3 (VT A3) extracted from European mistletoe
      (Viscum album L.) has been solved using the anomalous diffraction of the native S
      atoms measured in-house with Cu Kalpha radiation to a resolution of 2.2 A and
      truncated to 2.5 A. A 1.75 A resolution synchrotron data set was used for phase
      expansion and refinement. An innovation in the dual-space substructure-solution
      program SHELXD enabled the individual S atoms of the disulfide bonds to be
      located using the Cu Kalpha data; this resulted in a marked improvement in the
      phasing compared with the use of super-S atoms. The VT A3 monomer consists of 46
      amino acids with three disulfide bridges and has an overall fold resembling the
      canonical architecture of the alpha- and beta-thionins, a capital letter L. The
      asymmetric unit consists of two monomers related by a local twofold axis and held
      together by hydrophobic interactions between the monomer units. One phosphate
      anion (confirmed by 31P-NMR and MS) is associated with each monomer.

PMID- 14646071
TI  - Three-dimensional atomic structure of a catalytic subunit mutant of human protein
      kinase CK2.
AB  - The three-dimensional crystal structure of the triple-point mutant of the
      catalytic subunit of human protein kinase CK2alpha has been determined at 2.4 A
      resolution. Microcrystals of mutant CK2 catalytic subunit were obtained by a
      protein-crystallization method based on thin-film nanotechnology. These
      microcrystals (of about 20 micro m in diameter) were used for diffraction data
      collection by means of the microfocus beamline at the ESRF synchrotron. A
      comparison between the human protein kinase CK2alpha and the corresponding enzyme
      from a lower organism (Zea mays) is made.

PMID- 14646072
TI  - Refined structure of Pyrococcus furiosus ornithine carbamoyltransferase at 1.87
      A.
AB  - Using synchrotron radiation, X-ray data have been collected from Pyrococcus
      furiosus ornithine carbamoyltransferase (Pfu OTCase) to a maximal resolution of
      1.87 A, allowing the refinement of a previous structure at 2.7 A [Villeret et al.
      (1998), Proc. Natl Acad. Sci. USA, 95, 2801-2806]. Thanks to the high resolution
      of this refined structure, two sulfate ions and 191 water molecules could be
      localized directly from the electron-density maps. The identification of these
      molecules allowed a more rigorous description of the active site and the
      identification of residues involved in binding carbamoyl phosphate. The improved
      quality of the model resulted in a better definition of several loops and the
      various interfaces. The dodecameric protein is composed of four catalytic trimers
      disposed in a tetrahedral manner. The extreme thermal stability of Pfu OTCase is
      mainly the result of the strengthening of the intersubunit interactions in a
      trimer and oligomerization of the trimers into a dodecamer. Interfaces between
      monomers in a catalytic trimer are characterized by an increase in ion-pair
      networks compared with mesophilic OTCases. However, the interfaces between
      catalytic trimers in the dodecameric oligomer are mainly hydrophobic and also
      involve aromatic-aromatic and cation-pi interactions.

PMID- 14646073
TI  - Description of protein-DNA complexes in terms of electron-density topological
      features.
AB  - This paper presents a computer-modelling approach for the generation of low
      resolution representations of two protein-DNA complexes, NF-kappaB and HIF-1. The
      representation is obtained by topological analysis of electron-density maps at
      2.85 A crystallographic resolution, which leads to a set containing a limited
      number of critical points (CP). Analyses of the structure and properties of the
      CP graphs (density at peak position, volume and ellipticity), as well as
      comparisons with other reduced representations, are performed in order to assess
      the usefulness of such representations in molecular-docking applications at
      medium resolution.

PMID- 14646074
TI  - Structural studies of Proteus mirabilis catalase in its ground state, oxidized
      state and in complex with formic acid.
AB  - The structure of Proteus mirabilis catalase in complex with an inhibitor, formic
      acid, has been solved at 2.3 A resolution. Formic acid is a key ligand of
      catalase because of its ability to react with the ferric enzyme, giving a high
      spin iron complex. Alternatively, it can react with two transient oxidized
      intermediates of the enzymatic mechanism, compounds I and II. In this work, the
      structures of native P. mirabilis catalase (PMC) and compound I have also been
      determined at high resolution (2.0 and 2.5 A, respectively) from frozen crystals.
      Comparisons between these three PMC structures show that a water molecule present
      at a distance of 3.5 A from the haem iron in the resting state is absent in the
      formic acid complex, but reappears in compound I. In addition, movements of
      solvent molecules are observed during formation of compound I in a cavity located
      away from the active site, in which a glycerol molecule is replaced by a sulfate.
      These results give structural insights into the movement of solvent molecules,
      which may be important in the enzymatic reaction.

PMID- 14646075
TI  - Physical and structural studies on the cryocooling of insulin crystals.
AB  - Reflection profiles were analyzed from microgravity-grown ( micro g) and earth
      grown insulin crystals to measure mosaicity (eta) and to reveal mosaic domain
      structure and composition. The effects of cryocooling on single-domain and multi
      domain crystals were compared. The effects of cryocooling on insulin structure
      were also re-examined. Microgravity crystals were of larger volume, were more
      homogeneous and were of higher quality than earth crystals. Several micro g
      crystals contained a single mosaic domain which encompassed all or nearly all of
      the crystal with an eta(avg) of 0.005 degrees. The earth crystals varied in
      quality and all contained multiple domains with an eta(avg) of 0.031 degrees.
      Cryocooling caused a 43-fold increase in eta for micro g crystals (eta(avg) =
      0.217 degrees ) and an eightfold increase for earth crystals (eta(avg) = 0.246
      degrees ). These results indicate that very well ordered crystals are not
      completely protected from the stresses associated with cryocooling, especially
      when structural perturbations occur. However, there were differences in the
      reflection profiles. For multi-mosaic domain crystals, each domain individually
      broadened and separated from the other domains upon cryocooling. Cryocooling did
      not cause an increase in the number of domains. A crystal composed of a single
      domain retained this domain structure and the reflection profiles simply
      broadened. Therefore, an improved signal-to-noise ratio for each reflection was
      measured from cryocooled single-domain crystals relative to cryocooled multi
      domain crystals. The improved signal from micro g crystals, along with the
      increase in crystal size, facilitated the measurement of the weaker high
      resolution reflections. The observed broadening of reflection profiles indicates
      increased variation in unit-cell parameters, which may be linked to cryocooling
      associated structural changes and disorder.

PMID- 14646076
TI  - The structures of the PII proteins from the cyanobacteria Synechococcus sp. PCC
      7942 and Synechocystis sp. PCC 6803.
AB  - The PII proteins from the cyanobacteria Synechococcus sp. PCC 7942 and
      Synechocystis sp. PCC 6803 have been crystallized and high-resolution structures
      have been obtained using X-ray crystallography. The core of these new structures
      is similar to that of the PII proteins from Escherichia coli, although the
      structures of the T- and C-loops differ. The T-loop of the Synechococcus protein
      is ordered, but appears to be stabilized by crystal contacts. The same loop in
      the Synechocystis protein is disordered. The C-terminus of the Synechocystis
      protein is stabilized by hydrogen bonding to the same region of a
      crystallographically related molecule. The same terminus in the Synechococcus
      protein is stabilized by coordination with a metal ion. These observations are
      consistent with the idea that both the T-loop and the C-terminus of PII proteins
      are flexible in solution and that this flexibility may be important for receptor
      recognition. Sequence comparisons are used to identify regions of the sequence
      unique to the cyanobacteria.

PMID- 14646077
TI  - Structure of superoxide dismutase from Pyrobaculum aerophilum presents a
      challenging case in molecular replacement with multiple molecules, pseudo
      symmetry and twinning.
AB  - The crystal structure of superoxide dismutase from the hyperthermophilic
      crenarchaeon Pyrobaculum aerophilum was determined by molecular replacement at
      1.8 A resolution. The structure determination was made especially challenging by
      the large number of molecules (24) in the asymmetric unit, the presence of a
      pseudo-crystallographic twofold operator close to a twinning operator and the
      inability to detect twinning by conventional means. Molecular replacement
      proceeded at low resolution in pseudo (apparent) space group P3(2)12 and was
      facilitated by examination of the self-rotation function and native Patterson
      map. Refinement, however, stalled at an R factor of 40% when high-resolution data
      were included. Expanding to the lower symmetry space group P3(2) decreased R (to
      22%) and R(free) (to 26%), but not by as much as expected for the quality of
      data. Finally, despite the apparent lack of evidence from conventional twinning
      tests [i.e. plots of the second moment of I and N(Z) distributions], a twinning
      operator was included in the refinement, lowering R and R(free) to 16.2 and
      21.7%, respectively. The early detection of twinning appears to have been masked
      by a deviation in the expected intensity distribution caused by the presence of
      non-crystallographic translational symmetry. These findings suggest the
      importance of testing twinning operators in cases where pseudo-translational
      symmetry can explain negative results from conventional twinning tests. The
      structure reveals a tetrameric assembly with 222 symmetry, similar to superoxide
      dismutase structures from other organisms. The current structural model
      represents the metal-free state of the enzyme.

PMID- 14646078
TI  - Effective electron-density map improvement and structure validation on a Linux
      multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web
      Service.
AB  - Anticipating a continuing increase in the number of structures solved by
      molecular replacement in high-throughput crystallography and drug-discovery
      programs, a user-friendly web service for automated molecular replacement, map
      improvement, bias removal and real-space correlation structure validation has
      been implemented. The service is based on an efficient bias-removal protocol,
      Shake&wARP, and implemented using EPMR and the CCP4 suite of programs, combined
      with various shell scripts and Fortran90 routines. The service returns improved
      maps, converted data files and real-space correlation and B-factor plots. User
      data are uploaded through a web interface and the CPU-intensive iteration cycles
      are executed on a low-cost Linux multi-CPU cluster using the Condor job-queuing
      package. Examples of map improvement at various resolutions are provided and
      include model completion and reconstruction of absent parts, sequence correction,
      and ligand validation in drug-target structures.

PMID- 14646079
TI  - Structure of an insect delta-class glutathione S-transferase from a DDT-resistant
      strain of the malaria vector Anopheles gambiae.
AB  - Glutathione S-transferases (GSTs) are a major family of detoxification enzymes
      which possess a wide range of substrate specificities. Most organisms possess
      many GSTs belonging to multiple classes. Interest in GSTs in insects is focused
      on their role in insecticide resistance; many resistant insects have elevated
      levels of GST activity. In the malaria vector Anopheles gambiae, elevated GST
      levels are associated with resistance to the organochlorine insecticide DDT
      [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane]. This mosquito is the source of
      an insect GST, agGSTd1-6, which metabolizes DDT and is inhibited by a number of
      pyrethroid insecticides. The crystal structure of agGSTd1-6 in complex with its
      inhibitor S-hexyl glutathione has been determined and refined at 2.0 A
      resolution. The structure adopts a classical GST fold and is similar to those of
      other insect delta-class GSTs, implying a common conjugation mechanism. A
      structure-based model for the binding of DDT to agGSTd1-6 reveals two subpockets
      in the hydrophobic binding site (H-site), each accommodating one planar p
      chlorophenyl ring.

PMID- 14646080
TI  - Structure of rabbit-muscle glyceraldehyde-3-phosphate dehydrogenase.
AB  - The crystal structure of the tetrameric form of D-glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) isolated from rabbit muscle was solved at 2.4 A resolution
      after careful dynamic light-scattering experiments to find a suitable buffer for
      crystallization trials. The refined model has a crystallographic R factor of
      20.3%. Here, the first detailed model of a mammalian GAPDH is presented. The
      cofactor NAD(+) (nicotinamide adenine dinucleotide) is bound to two subunits of
      the tetrameric enzyme, which is consistent with the negative cooperativity of
      NAD(+) binding to this enzyme. The structure of rabbit-muscle GAPDH is of
      interest because it shares 91% sequence identity with the human enzyme; human
      GAPDH is a potential target for the development of anti-apoptotic drugs. In
      addition, differences in the cofactor-binding pocket compared with the homology
      model structure of GAPDH from the malaria parasite Plasmodium falciparum could be
      exploited in order to develop novel selective and potential antimalaria drugs.

PMID- 14646081
TI  - Low-temperature water reconstruction in concanavalin A, with implications for
      controlled protein crystal annealing.
AB  - Flash-cooled crystals of the I222 form of concanavalin A undergo a sharp non
      destructive non-reversible phase transition upon warming to between 160 and 165
      K, characterized by an anomalous increase in unit-cell volume. The expansion is
      anisotropic and primarily affects the b and c axes. Three sets of 1.7 A X-ray
      diffraction data were collected from one crystal: immediately after flash-cooling
      (130 K), after slow warming to 170 K and after re-cooling to 130 K. Measurable
      changes in reflection width after the transition were apparent. Each data set was
      collected under very similar conditions (aside from temperature). Structures
      refined against each data set using a powerful phase-bias reduction algorithm
      indicate negligible rearrangement of the protein molecule and its first hydration
      shell. Further away from the protein surface, on the edge of the fully disordered
      solvent regions, a small number of more dramatic changes were apparent. Little is
      known about the behaviour of water confined within dimensionally restricted
      spaces, but solvent cavities and channels in protein crystals provide a rich
      source of reproducible nanoscale water assemblies. This paper presents
      information on the behaviour of water confined within protein cavities in
      relation to the physics of protein crystal annealing.

PMID- 14646082
TI  - Acetobacter turbidans alpha-amino acid ester hydrolase: merohedral twinning in
      P21 obscured by pseudo-translational NCS.
AB  - The structure elucidation of the alpha-amino acid ester hydrolase from
      Acetobacter turbidans by molecular replacement is described. In the monoclinic
      crystal, the molecules are related by both rotational and pseudo-crystallographic
      translational NCS (non-crystallographic symmetry). Refinement of the structure
      converged at unacceptably high R factors. After re-evaluation of the data, it was
      found that the crystal was merohedrally twinned, with a high twinning fraction.
      It is shown that the pseudo-crystallographic NCS causes aberrant behaviour of
      conventional twinning indicators, which explains why the twinning was only
      realized at the refinement stage.

PMID- 14646083
TI  - Making the most of two crystals: structural analysis of a conserved hypothetical
      protein using native gel screening and SAD phasing.
AB  - The protein PAE2307 is a member of a protein family of unknown function which is
      conserved among a number of bacterial and archaeal species. The protein was
      overexpressed in Escherichia coli, purified and crystallized in two crystal
      forms. The prevalent form was twinned, but the other diffracted to 1.45 A
      resolution. The non-twinned crystals proved difficult to reproduce, so screening
      of potential heavy-atom derivatives by native polyacrylamide gel electrophoresis
      was used to establish suitable derivatization conditions. This process enabled
      the production of a K(2)Pt(NO2)4 derivative that was used to collect a single
      wavelength anomalous diffraction (SAD) data set from the only available crystal.
      Phase information of high quality was obtained, enabling the calculation of an
      interpretable electron-density map.

PMID- 14646084
TI  - Purification, crystallization and X-ray diffraction analysis of the extracellular
      part of the human Fc receptor for IgA, FcalphaRI (CD89).
AB  - FcalphaRI is the predominant receptor for IgA in the serum. Nevertheless, the
      interaction between the molecules that finally leads to an immune response is
      poorly understood. To investigate the structural requirements for IgA binding,
      the extracellular region of FcalphaRI was cloned and overexpressed in Escherichia
      coli. The resulting inclusion-body protein was refolded and purified. Despite its
      deglycosylated state, this recombinant FcalphaRI retained its ability to bind
      human IgA. The protein crystallized spontaneously as microcrystalline needles.
      Recrystallization yielded crystals belonging to a primitive monoclinic space
      group. A complete 2.8 A resolution X-ray diffraction data set was collected using
      synchrotron radiation.

PMID- 14646085
TI  - Crystallization and preliminary crystallographic analysis of the extracellular
      fragment of FcalphaRI/CD89.
AB  - Crystals of the extracellular fragment of FcalphaRI/CD89 have been grown at 291 K
      using PEG 8000 as precipitant. The diffraction pattern of the selenomethionine
      (SeMet) derivative crystal extended to 2.1 A resolution at SPring-8, Japan. The
      crystals belong to space group C222(1), with unit-cell parameters a = 59.0, b =
      69.4, c = 106.3 A, alpha = beta = gamma = 90 degrees. The presence of one
      molecule per asymmetric unit gives a crystal volume per protein mass (V(M)) of
      3.12 A(3) Da(-1) and a solvent content of 60.2% by volume. A full set of X-ray
      diffraction data were collected to 2.1 A from an SeMet-derivative crystal.

PMID- 14646086
TI  - Crystallization and preliminary X-ray diffraction analysis of Mycobacterium
      smegmatis Dps.
AB  - Three crystal forms of a DNA-binding protein from stationary phase cells (Dps) of
      Mycobacterium smegmatis have been grown. They are hexagonal, tetragonal and
      cubic. The structure of the cubic form, which has one subunit in the asymmetric
      unit, has been solved using the molecular-replacement method. The application of
      the crystallographic symmetry operations on the subunit leads to eight dodecamers
      with 23 symmetry in the unit cell.

PMID- 14646087
TI  - Crystallization of a novel alpha-amylase, AmyB, from the thermophilic halophile
      Halothermothrix orenii.
AB  - This is a report on the structure determination of AmyB, the second alpha-amylase
      from Halothermothrix orenii, by X-ray crystallography. This bacterium was
      isolated from saltpans where conditions consisted of both high temperatures and
      high NaCl content. AmyB is a 599-residue protein which is stable and
      significantly active at 358 K in starch solution containing up to 10%(w/v) NaCl.
      The purified recombinant AmyB protein crystallizes in the monoclinic space group
      C2, with unit-cell parameters a = 225.85, b = 77.16, c = 50.13 A, beta = 99.32
      degrees, using the hanging-drop vapour-diffusion method. The crystal diffracts X
      rays to a resolution limit of 1.97 A.

PMID- 14646088
TI  - Expression and crystallographic characterization of the extracellular domain of
      human natural killer cell triggering receptor NKp46.
AB  - Human natural killer (NK) cells are regulated in their cytolytic activity by a
      delicate interplay between activating and inhibitory signals related to distinct
      families of triggering and inhibitory receptor proteins. NKp46 is a major NK cell
      specific triggering receptor involved in the recognition and lysis of human and
      murine tumour and virally infected cells. It consists of an extracellular
      portion, composed of two Ig-like domains, a transmembrane segment and a small
      cytoplasmic domain. To shed light on the molecular-recognition events involved in
      NK cytotoxicity triggering mechanisms, the NKp46 extracellular region was cloned,
      overexpressed, refolded and crystallized. X-ray diffraction data could be
      collected to a resolution limit of 1.93 A. Crystals of the NKp46 extracellular
      region belong to the hexagonal space group P6(1) (or P6(5)), with unit-cell
      parameters a = b = 85.48, c = 59.91 A, gamma = 120 degrees; the asymmetric unit
      contains one protein chain (197 amino acids).

PMID- 14646089
TI  - Crystallization of RusA Holliday junction resolvase from Escherichia coli.
AB  - Crystals of the Escherichia coli Holliday junction resolvase RusA have been
      obtained using the hanging-drop method and characterized. The crystals have a
      primitive monoclinic form and belong to space group P2(1). The V(M) value
      suggests the presence of two copies of the monomer in the asymmetric unit. A full
      three-wavelength MAD data collection on a selenomethionine-incorporated form has
      been undertaken and structure determination is under way using data collected to
      2.1 A resolution.

PMID- 14646090
TI  - Preliminary X-ray diffraction analysis of octaprenyl pyrophosphate synthase
      crystals from Thermotoga maritima and Escherichia coli.
AB  - Octaprenyl pyrophosphate synthase (OPPs) catalyzes the condensation of five
      isopentenyl pyrophosphates with farnesyl pyrophosphate to generate C(40)
      octaprenyl pyrophosphate. The enzymes from the hyperthermophilic bacterium
      Thermotoga maritima and from the mesophilic Escherichia coli were expressed in E.
      coli and the recombinant proteins were purified and crystallized. The T. maritima
      OPPs crystals belong to space group P42(1)2, with unit-cell parameters a = b =
      151.53, c = 69.72 A. The E. coli OPPs crystals belong to space group C222(1),
      with unit-cell parameters a = 247.66, b = 266.10, c = 157.93 A. Diffraction data
      were collected at 100 K using synchrotron radiation and an in-house X-ray source.
      Structure determination of T. maritima OPPs has been carried out using MIR data
      sets at 2.8 A resolution. The asymmetric unit contains one dimer. An initial
      model with 280 residues per subunit has been built and refined to 2.28 A
      resolution. It shows mostly helical structure and resembles that of avian
      farnesyl pyrophosphate synthase.

PMID- 14646091
TI  - Crystallization and preliminary crystallographic studies of the C-terminal domain
      of human FKBP52.
AB  - FKBP52 is a high-molecular-weight immunophilin belonging to the FKBP (FK506
      binding protein) family. FKBP52 is one of several chaperone proteins associated
      with untransformed steroid receptors in steroid receptor-hsp90 heterocomplexes.
      Here, the C-terminal domain (amino acids 145-459) has been cloned, overexpressed
      and purified. Crystals were obtained using the hanging-drop vapour-diffusion
      technique with ammonium sulfate as precipitant in 0.1 M Tris pH 8.0 solution.
      Diffraction data to 2.7 A were collected from a selenomethionine-containing
      crystal belonging to space group C222(1), with unit-cell parameters a = 114.4, b
      = 143.1, c = 171.2 A, alpha = beta = gamma = 90 degrees. There are three
      molecules per asymmetric unit.

PMID- 14646092
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of S
      formylglutathione hydrolase from Arabidopsis thaliana: effects of pressure and
      selenomethionine substitution on space-group changes.
AB  - S-Formylglutathione hydrolase (SFGH) has activity toward several xenobiotic
      carboxyesters and catalyses the final step of formaldehyde detoxification: the
      hydrolysis of S-formylglutathione to formate and glutathione. The Arabidopsis
      thaliana enzyme (AtSFGH) was crystallized in space group C2, with unit-cell
      parameters a = 128.5, b = 81.1, c = 94.3 A, beta = 93.3 degrees and three
      molecules in the asymmetric unit. A second crystal form of AtSFGH could be
      obtained by pressurizing the monoclinic crystals at 2 MPa for 30 min. The
      resulting space group is either P3(1)21 or P3(2)21, with unit-cell parameters a =
      75.1, c = 92.8 A and one molecule in the asymmetric unit. Crystallographic data
      have been collected for both crystal forms to resolutions of 1.7 A for the
      monoclinic crystal and 1.6 A for the trigonal crystal. The structure has been
      solved by MAD phasing using a three-wavelength data set collected from a
      monoclinic crystal of selenomethionine-labelled AtSFGH.

PMID- 14646093
TI  - Crystallization and preliminary X-ray analysis of the small component of 4
      hydroxyphenylacetate 3-monooxygenase (HpaC) and its cofactor complex from Thermus
      thermophilus HB8.
AB  - The small component of 4-hydroxyphenylacetate 3-monooxygenase (HpaC) is an NADH
      oxidoreductase containing a flavin molecule as a cofactor. HpaC reduces a flavin
      molecule and reduced flavin is subsequently supplied to the large component of 4
      hydroxyphenylacetate 3-monooxygenase (HpaB). The HpaC protein from Thermus
      thermophilus HB8 has been overexpressed in Escherichia coli and crystallized.
      During purification, the eluted HpaC protein solutions were separated into
      colourless and yellow-coloured fractions (i.e. apo-HpaC and HpaC-flavin complex,
      respectively). Crystals of apo-HpaC grown in 5%(v/v) isopropyl alcohol, 0.1 M
      HEPES-NaOH pH 7.0, 40%(w/v) polyethylene glycol (PEG) 4000 and 10%(v/v) glycerol
      diffracted X-rays to a resolution of 1.85 A, whereas crystals of the HpaC-flavin
      complex grown in 20%(w/v) PEG 1000, 10%(w/v) PEG 8000 and 10%(v/v) glycerol
      diffracted X-rays to a resolution of 1.3 A. Both crystals belong to the
      monoclinic system, space group P2(1), with similar unit-cell parameters.
      Selenomethionyl protein crystals of the HpaC-flavin complex grown under similar
      conditions to the native crystals diffracted X-rays to a resolution of 1.8 A.
      They also belong to the monoclinic space group P2(1), but are not isomorphous to
      crystals of the HpaC-flavin complex of the native protein. MAD data for structure
      determination were successfully collected using these crystals.

PMID- 14646094
TI  - Bacterial expression, purification and preliminary X-ray crystallographic
      characterization of the invertase inhibitor Nt-CIF from tobacco.
AB  - Acid invertases catalyzing the breakdown of sucrose are regulated at the post
      translational level by extracellular inhibitory proteins of 16-20 kDa molecular
      weight in a pH-dependent manner. Little is known about the characteristics of the
      underlying protein-protein interaction. Here, the expression, purification,
      characterization, crystallization and initial X-ray analysis of a biologically
      active invertase inhibitor Nt-CIF from tobacco is reported. Four crystal forms
      covering a wide pH range have been obtained and data sets at resolutions higher
      than 2.5 A have been collected.

PMID- 14646095
TI  - Purification, crystallization and preliminary X-ray analysis of a water-soluble
      chlorophyll protein from Brassica oleracea L. var. acephala (kale).
AB  - A water-soluble chlorophyll protein (WSCP) with a chlorophyll a:b ratio of 6:1
      from Brassica oleracea L. var. acephala (kale) was purified and crystallized by
      the hanging-drop vapour-diffusion method using PEG 8000 and zinc acetate as
      precipitants. The crystal belongs to the hexagonal space group P6(4)22, with unit
      cell parameters a = b = 162.2, c = 38.7 A. A native data set was collected to
      2.80 A resolution at 293 K using Cu Kalpha radiation from a rotating-anode
      generator. Preliminary analysis via molecular replacement identified one kale
      WSCP monomer in the asymmetric unit. The crystal packing showed a tetrameric
      structure for kale WSCP, as suggested by previous biochemical studies of WSCPs
      from Brassicaceae plants.

PMID- 14646096
TI  - Expression, crystallization and preliminary X-ray crystallographic studies of
      Arthrobacter globiformis inulin fructotransferase.
AB  - A recombinant form of Arthrobacter globiformis inulin fructotransferase (DFAIII
      producing) has been overexpressed in Escherichia coli and purified to
      homogeneity. Crystals were obtained at 293 K by the hanging-drop vapour-diffusion
      technique using 0.1 M Na HEPES pH 7.5 buffer containing 1.5 M lithium sulfate as
      a precipitant. Crystals of the recombinant wild-type enzyme diffracted to better
      than 1.5 A at 100 K using a synchrotron-radiation source at the Photon Factory.
      The crystal belonged to space group R32, with unit-cell parameters a = b = 92.02,
      c = 229.82 A in the hexagonal axes. Assuming the presence of one molecule in the
      asymmetric unit, the V(M) value for the crystal was 2.15 A(3) Da(-1), indicating
      a solvent content of 42.8%. Selenomethionine-derivative crystals belonged to a
      different space group, C2, with unit-cell parameters a = 159.32, b = 91.92, c =
      92.58 A, beta = 125.06. Matthews coefficient calculations suggested that the C2
      selenomethionine-derivative crystal contained three molecules per asymmetric
      unit.

PMID- 14646097
TI  - Crystallization and preliminary X-ray crystallographic studies of alpha
      galactosidase I from Mortierella vinacea.
AB  - alpha-Galactosidases catalyze the hydrolysis of a galactosyl residue from
      galactooligosaccharides and galactopolysaccharides. alpha-Galactosidase I from
      Mortierella vinacea was crystallized in two crystal forms using the hanging-drop
      vapour-diffusion method. Type 1 crystals belonged to space group I422, with unit
      cell parameters a = b = 142.4, c = 131.5 A, and diffracted to beyond 2.1 A
      resolution, while type 2 crystals belonged to space group P4, with unit-cell
      parameters a = b = 100.9, c = 102.7 A, and diffracted to beyond 1.6 A resolution.
      This enzyme crystallized as a glycoprotein tetramer and the tetrameric structure
      was located around the crystallographic fourfold axis.

PMID- 14646098
TI  - Crystallization and X-ray diffraction of 5'-fluoro-5'-deoxyadenosine synthase, a
      fluorination enzyme from Streptomyces cattleya.
AB  - Organofluorine compounds are widely prepared throughout the chemicals industry,
      but their prepararion generally requires harsh fluorinating reagents and non
      aqueous solvents. On the other hand, biology has hardly exploited organofluorine
      compounds. A very few organisms synthesize organofluorine metabolites, suggesting
      they have evolved a mechanism to overcome the kinetic desolvation barrier to
      utilizing F(-)(aq). Here, the purification and crystallization of an enzyme from
      Streptomyces cattleya which is responsible for the synthesis of the C-F bond
      during fluoroacetate and 4-fluorothreonine biosynthesis is reported. The protein
      crystallizes in space group C222(1), with unit-cell parameters a = 75.9, b =
      130.3, c = 183.4 A, alpha = beta = gamma = 90 degrees. Data were recorded to 1.9
      A at the ESRF. The structure of the protein should provide important insights
      into the biochemical process of C-F bond formation.

PMID- 14646099
TI  - Crystallization and preliminary X-ray crystallographic studies of NADP-dependent
      3-hydroxyisobutyrate dehydrogenase from Thermus thermophilus HB8.
AB  - 3-Hydroxyisobutyrate, a central metabolite in the valine catabolic pathway, is
      reversibly oxidized to methylmalonate semialdehyde by a specific NADP-dependent
      dehydrogenase (HIBADH). HIBADH from Thermus thermophilus HB8 has been
      overexpressed in Escherichia coli and crystallized by the microbatch method using
      lithium chloride as a precipitant at 296 K. X-ray diffraction data have been
      collected to 1.80 A resolution at 100 K using synchrotron radiation. The crystals
      belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a
      = 85.878, b = 106.367, c = 168.639 A. A homotetramer of HIBADH is likely to be
      present in the asymmetric unit, giving a V(M) of 3.0 A(3) Da(-1) and a solvent
      content of 59.3%.

PMID- 14646100
TI  - Crystallization and preliminary crystallographic analysis of human serine
      dehydratase.
AB  - L-Serine dehydratase (SDH) catalyzes the pyridoxal phosphate (PLP) dependent
      deamination of L-serine to yield pyruvate. Recombinant human serine dehydratase
      was crystallized by the hanging-drop vapour-diffusion method. Crystals were grown
      at 291 K using (NH4)(2)SO4 as precipitant. Diffraction data were obtained to a
      resolution of 2.5 A from a single frozen crystal using Cu Kalpha radiation. The
      crystal belongs to space group I422, with unit-cell parameters a = 157.4, b =
      157.4, c = 59.2 A, alpha = beta = gamma = 90 degrees. The asymmetric unit
      contains one molecule and has a solvent content of about 46%.

PMID- 14646101
TI  - Crystallization and preliminary crystallographic characterization of an SH3
      domain from the IB1 scaffold protein.
AB  - IB1 is a mammalian scaffold protein that interacts with components of the c-Jun N
      terminal kinase (JNK) signal-transduction pathway mainly via its protein-protein
      interaction domains. Crystallization of the key Src homology 3 (SH3) domain of
      IB1 has been achieved. Crystallization experiments with unmodified protein and
      deliberately oxidized protein have led to different crystal forms. X-ray data
      have been collected to 3.0 A resolution from a crystal form with rectangular
      prism morphology. These crystals are orthorhombic (P2(1)2(1)2(1)), with unit-cell
      parameters a = 45.9, b = 57.0, c = 145.5 A. These are the first crystallographic
      data on a scaffold molecule such as IB1 to be reported.

PMID- 14646102
TI  - Crystallization and preliminary X-ray diffraction data of Mycobacterium
      tuberculosis FbpC1 (Rv3803c).
AB  - The heterotrimeric antigen 85 complex (Ag85) is a major component of the cell
      wall of Mycobacterium tuberculosis and consists of three abundantly secreted
      proteins (FbpA, FbpB and FbpC2). These play key roles in the pathogenesis of
      tuberculosis and in maintaining cell-wall integrity. A homologue of the Ag85
      subunits ( approximately 40% identity) was recently annotated in the M.
      tuberculosis genome as FbpC1. Unlike the Ag85-complex components, FbpC1 lacks
      mycolyltransferase activity and its function remains to be established. In order
      to aid functional characterization, FbpC1 has been crystallized. At room
      temperature, tetragonal crystals of FbpC1 were obtained belonging to space group
      P4(1)2(1)2 (unit-cell parameters a = b = 109.9, c = 61.8 A), yet when frozen the
      crystals underwent a phase transition to orthorhombic symmetry, space group
      P2(1)2(1)2(1) (a = 59.9, b = 108.9, c = 109.9 A). Diffraction data complete to
      1.7 A resolution were recorded at 100 K at the synchrotron.

PMID- 14646103
TI  - Crystallization and preliminary neutron analysis of the dissimilatory sulfite
      reductase D (DsrD) protein from the sulfate-reducing bacterium Desulfovibrio
      vulgaris.
AB  - Dissimilatory sulfite reductase D (DsrD) from Desulfovibrio vulgaris has been
      crystallized for a neutron diffraction study. The initial crystals obtained were
      too small for the neutron experiment. In order to obtain a larger crystal (>1
      mm3), a combination of two techniques was developed to determine the optimum
      crystallization conditions: a crystallization phase diagram was obtained,
      followed by crystal-quality assessment via X-ray diffraction. Using conditions
      determined in this manner, a large single crystal (1.7 mm3) of DsrD protein was
      subsequently grown in D(2)O solution by the macroseeding technique. A neutron
      diffraction experiment was carried out using the BIX-3 diffractometer at the
      Japan Atomic Energy Research Institute (JAERI), collecting data to 2.4 A
      resolution from an optimized crystal.

PMID- 14646104
TI  - Purification, partial characterization and crystallization of acucetin, a protein
      containing both disintegrin-like and cysteine-rich domains released by auto
      proteolysis of a P-III-type metalloproteinase AaH-IV from Agkistrodon acutus
      venom.
AB  - AaH-IV, a P-III-type metalloproteinase found in Agkistrodon acutus venom, readily
      cleaves itself to release a stable protein named acucetin at 310 K under neutral
      and weakly alkaline conditions. A partial amino-acid residue sequence of acucetin
      indicates that the protein has a high homology to snake-venom proteins containing
      both disintegrin-like and cysteine-rich domains. Acucetin has been crystallized
      in space group R32, with hexagonal unit-cell parameters a = b = 155.98, c = 76.07
      A. The V(M) value of about 2.97 A(3) Da(-1) suggests the presence of only one
      molecule in the asymmetric unit.

PMID- 14646105
TI  - Crystallization of CprB, an autoregulator-receptor protein from Streptomyces
      coelicolor A3(2).
AB  - CprB, an autoregulator-receptor protein from Streptomyces coelicolor A3(2), was
      crystallized by the hanging-drop vapour-diffusion method using polyethylene
      glycol 6000 as a precipitant. Three crystal forms (I, II and III) were obtained;
      crystal forms I and II were useful for structure determination. Form I crystals
      belong to an orthorhombic system with space group P2(1)2(1)2(1) and diffracted to
      better than 2.4 A. Form II crystals belong to a tetragonal system with space
      group P4(1(3))2(1)2.

PMID- 14646106
TI  - Crystallization and preliminary X-ray analysis of N-acetyl-1-D-myo-inosityl-2
      deoxy-alpha-D-glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis.
AB  - Mycobacteria synthesize mycothiol (MSH) as a low-molecular-weight thiol that
      protects against oxidative stress in a similar role to that of glutathione in
      many other species. The absence of MSH in mammals suggests that enzymes from its
      biosynthetic pathway in Mycobacterium tuberculosis could be useful targets for
      drug design. The gene for MshB (Rv1170), the enzyme that catalyses the second
      step in MSH biosynthesis in M. tuberculosis, has been cloned and the protein has
      been expressed in Escherichia coli both in native and SeMet-substituted forms and
      crystallized in two crystal forms. One of these, prepared in the presence of beta
      octylglucoside as a key additive, is suitable for high-resolution X-ray
      structural analysis. The crystals are orthorhombic, with unit-cell parameters a =
      71.69, b = 83.74, c = 95.65 A, space group P2(1)2(1)2(1) and two molecules in the
      asymmetric unit. X-ray diffraction data to 1.9 A resolution have been collected.

PMID- 14646107
TI  - Expression, purification, crystallization and preliminary crystallographic
      analysis of phosphoserine aminotransferase from Bacillus alcalophilus.
AB  - Phosphoserine aminotransferase (PSAT; EC 2.6.1.52) from Bacillus alcalophilus, an
      obligatory alkalophile with optimum growth at pH 10.6, was overexpressed in
      Escherichia coli, purified and crystallized under two different conditions using
      the hanging-drop vapour-diffusion method. Crystals were obtained using trisodium
      citrate dihydrate or PEG 400 as a precipitating agent. Crystals grown in the
      presence of trisodium citrate belong to the orthorhombic space group C222(1),
      with unit-cell parameters a = 105.6, b = 136.6, c = 152.0 A, and those grown in
      the presence of PEG 400 belong to the orthorhombic space group P2(1)2(1)2, with
      unit-cell parameters a = 143.7, b = 84.3, c = 67.4 A. Complete data sets were
      collected to 1.7 and 1.6 A resolution, respectively, at 100 K using synchrotron
      radiation. Analysis of the structure of B. alcalophilus PSAT may reveal
      structural features that contribute to enzyme adaptability at high pH values.

PMID- 14646108
TI  - Crystallization and preliminary X-ray analysis of the glycogen synthase from
      Pyrococcus abyssi.
AB  - Glycogen synthase catalyzes the transfer of glucosyl residues from ADP- or UDP
      glucose to the non-reducing end of a growing alpha-1,4-glucan chain. To date, no
      crystallographic structure of an animal/fungal glycogen synthase (family 3 of the
      glycosyl transferases) or a bacterial/plant glycogen/starch synthase (family 5)
      has been reported. This paper describes the recombinant expression,
      crystallization and preliminary X-ray analysis of the glycogen synthase from the
      hyperthermophilic archaeon Pyrococcus abyssi, the smallest enzyme of the members
      of families 3 and 5 of the glycosyl transferases. Crystals from this protein and
      from its selenomethionyl variant were grown in 100 mM sodium citrate pH 5.6
      containing 20% PEG and 20% dioxane by the hanging-drop vapour-diffusion method at
      293 K. The crystals, which grew as thin needles, diffracted to 3.5 A resolution
      and belong to space group C2, with unit-cell parameters a = 202, b = 73, c = 149
      A, beta = 131 degrees. The crystallographic and biochemical data are consistent
      with either a dimer or a tetramer in the crystal asymmetric unit and a volume
      solvent content of 70 or 39%, respectively.

PMID- 14646109
TI  - Crystallization of [Fe3S4]-ferredoxin from the hyperthermophile archaeon
      Pyrococcus furiosus.
AB  - Recombinant Pyrococcus furiosus ferredoxin with a [Fe3S4]-cluster was
      crystallized through steps of optimization and X-ray diffraction data were
      collected from several crystal forms. Flat plate-like crystals were grown by
      hanging-drop vapour diffusion. The precipitant used was 30% PEG 400; the pH was
      varied between 7.0 and 8.0 and hexaamminecobalt(III) chloride was essential for
      crystal formation. The best crystals belong to space group P2(1), with unit-cell
      parameters a = 31.23, b = 47.51, c = 52.03 A, beta = 103.86 degrees, and diffract
      to 1.5 A resolution.

PMID- 14646110
TI  - Crystallization and phasing of alanine dehydrogenase from Archaeoglobus fulgidus.
AB  - Alanine dehydrogenase (AlaDH) from the hyperthermophilic archaeon Archaeoglobus
      fulgidus is a dimer of 35 kDa chains. The archaeal enzyme appears to represent a
      new class of AlaDH that is not homologous to bacterial AlaDH enzymes, but has
      close evolutionary links to the broad ornithine cyclodeaminase/micro-crystallin
      family, which includes human thyroid hormone binding protein, which has 30%
      sequence identity to the A. fulgidus gene. The enzyme has been cloned, shown to
      catalyze the NAD-dependent interconversion of alanine and pyruvate and
      crystallized in several forms. Although the purified protein crystallized readily
      under many conditions, most of the crystals diffracted weakly or not at all. One
      polymorph growing in space group P2(1)2(1)2(1) has non-crystallographic symmetry
      that becomes crystallographic, changing the space group to P2(1)2(1)2, upon
      binding iridium or samarium. Before and after derivatization, these crystals
      diffracted to 2.5 A using synchrotron radiation. Multiwavelength diffraction data
      were collected from the non-isomorphous iridium derivative, enabling structure
      determination.

PMID- 14646111
TI  - Crystallization and preliminary X-ray crystallographic analysis of human
      peptidylarginine deiminase V.
AB  - Human peptidylarginine deiminase V (PAD V) is a post-translational enzyme that
      catalyzes the conversion of arginine residues in protein into citrulline residues
      in the presence of calcium ion. Crystals of PAD V have been grown at 293 K using
      polyethylene glycol monomethylether as a precipitant. Crystals diffracted beyond
      2.7 A resolution at 100 K at the SPring-8 synchrotron-radiation source. The
      crystal belongs to space group C2, with unit-cell parameters a = 144.6, b = 60.4,
      c = 113.4 A, beta = 123.6 degrees. The asymmetric unit contains one molecule,
      with a V(M) of 2.56 A(3) Da(-1) and a solvent content of 56.1%. A full set of X
      ray diffraction data was collected to 2.8 A resolution with a completeness of
      97.5%. Heavy-atom derivatives have been successfully prepared and structure
      analysis is in progress.

PMID- 14646112
TI  - Crystallization and preliminary X-ray crystallographic analysis of the Hsp100
      chaperone ClpB from Thermus thermophilus.
AB  - ClpB from Thermus thermophilus (TClpB) has been crystallized by the vapour
      diffusion method in the presence of adenosine 5'-(beta,gamma-imido)triphosphate
      (AMPPNP) and adenosine 5'-(gamma-thio)triphosphate (ATPgammaS), respectively.
      Complete native data sets have been collected from frozen crystals, which
      belonged to the primitive orthorhombic space group P2(1)2(1)2(1) with unit-cell
      parameters a = 109.2, b = 139.6, c = 213.0 A, alpha = beta = gamma = 90 degrees.

PMID- 14646113
TI  - Order and disorder in crystals of hexameric NTPases from dsRNA bacteriophages.
AB  - The packaging of genomic RNA in members of the Cystoviridae is performed by P4, a
      hexameric protein with NTPase activity. Across family members such as Phi6, Phi8
      and Phi13, the P4 proteins show low levels of sequence identity, but presumably
      have similar atomic structures. Initial structure-determination efforts for P4
      from Phi6 and Phi8 were hampered by difficulties in obtaining crystals that gave
      ordered diffraction. Diffraction from crystals of full-length P4 showed a variety
      of disorder and anisotropy. Subsequently, crystals of Phi13 P4 were obtained
      which yielded well ordered diffraction to 1.7 A. Comparison of the packing
      arrangements of P4 hexamers in different crystal forms and analysis of the
      disorder provides insights into the flexibility of this family of proteins, which
      might be an integral part of their biological function.

PMID- 14646114
TI  - Structure of d(ITITACAC) complexed with distamycin at 1.6 A resolution.
AB  - The crystal structure of the DNA octamer d(ITITACAC)(2) complexed with distamycin
      has been determined at 1.6 A resolution and refined to a final R(work) and
      R(free) of 17.0 and 20.7%, respectively. Two molecules of distamycin bind to the
      DNA duplex in an antiparallel side-by-side fashion. Each drug molecule covers
      five base pairs of the DNA duplex, with its amide groups hydrogen-bonding to
      bases in the proximal DNA strand. These two antiparallel drug molecules are
      stacked together with the pyrrole rings of one molecule stacking against the
      amide groups of the other. The present structure emphasizes the features of
      alternating DNA octamers in interaction with distamycin.

PMID- 14646115
TI  - Oils used in microbatch crystallization do not remove a detergent from the drops
      they cover.
AB  - In microbatch crystallizations, a small volume of protein solution is placed in
      contact with a large volume of oil. Detergents present in the water phase may be
      expected to migrate into the oil phase, which could have effects on the protein
      in solution. A new method is described in which detergent partitioning into the
      oil can be checked. The accuracy of this method is sufficiently high to estimate
      even very low partitioning coefficients. The measurements indicate that in the
      case of dodecyl maltoside, no significant loss of detergent will occur.

PMID- 14646116
TI  - Molecules of Escherichia coli MobB assemble into densely packed hollow cylinders
      in a crystal lattice with 75% solvent content.
AB  - The crystal structure of Escherichia coli MobB, an enzyme involved in the final
      step of molybdenum-cofactor biosynthesis, forms intertwined dimers. Each molecule
      consists of two segments and requires the second monomer for stable folding.
      Dimerization buries a quarter of the solvent-accessible area of the monomer.
      These dimers assemble into a hexagonal lattice with P6(4)22 symmetry and occupy
      only approximately 25% of the unit-cell volume. The symmetry-related dimers
      associate tightly into a helical structure with a diameter of 250 A and a pitch
      of 98 A. Two such helices are intertwined, shifted by 49 A along the sixfold
      axis. Within the crystal, these helices form thin-walled cylinders with an
      external diameter of 250 A and an internal diameter of 190 A. Their center is
      filled with solvent. These cylinders pack closely together, forming a hexagonal
      lattice with the highest possible packing density. This arrangement of dimers
      allows extensive intermolecular contacts with 75% solvent content in the crystal.

PMID- 14646117
TI  - Crystallization of the bovine ADP/ATP carrier is critically dependent upon the
      detergent-to-protein ratio.
AB  - The ADP/ATP carrier is an integral membrane protein located in the mitochondrial
      inner membrane. It mediates the exchange of cytosolic ADP for ATP generated in
      the mitochondrial matrix. Here, the purification and crystallization of the
      bovine ADP/ATP carrier in complex with the inhibitor carboxyatractyloside in the
      presence of LAPAO, an aminoxide detergent, is reported. High-quality crystals
      were only obtained when excess detergent was removed to reach a controlled
      detergent-to-protein ratio.

PMID- 14646118
TI  - Malonate: a versatile cryoprotectant and stabilizing solution for salt-grown
      macromolecular crystals.
AB  - Collection of quality data on high-energy synchrotron sources requires the
      selection of a cryoprotectant that allows protein crystals to be cryocooled
      without damage to the crystal and with suppression of ice formation. The use of
      sodium malonate as a versatile cryoprotectant for salt-grown protein crystals is
      presented here. In addition to its useful cryoprotectant properties, sodium
      malonate can also function as a versatile stabilizing solution that allows the
      manipulation, derivatization and ligand soaking of crystals grown from salt that
      may not be possible in the crystal mother liquor.

PMID- 14646119
TI  - Overview and new developments in softer X-ray (2A < lambda < 5A) protein
      crystallography.
AB  - New methodologies with synchrotron radiation and X-ray free electron lasers
      (XFELs) in structural biology are being developed. Recent trends in harnessing
      softer X-rays in protein crystallography for phase determination are described.
      These include reference to a data-collection test at 2.6 A wavelength with a
      lysozyme crystal on SRS station 7.2 (Helliwell, 1983) and also use of softer X
      rays (2 A wavelength) to optimise f " at the xenon L1 absorption edge in the
      Single Isomorphous Replacement Optimised Anomalous Scattering ('SIROAS')
      structure determination of apocrustacyanin A1 with four, partially occupied,
      xenon atoms (Cianci et al., 2001; Chayen et al., 2000). The hand of the protein
      was determined using the f " enhanced sulphur anomalous signal from six
      disulphides in the protein dimer of 40 kDa. In a follow-up study the single
      wavelength xenon L1-edge f " optimised data set alone was used for phase
      determination and phase improvement by solvent flattening etc. (CCP4 DM) (Olczak
      et al., 2003). Auto-tracing of the protein was feasible but required additional
      diffraction data at higher resolution. This latter could be avoided in future by
      using improved tilted detector settings during use of softer X-rays, i.e. towards
      back-scattering recording (Helliwell, 2002). The Olczak et al. study has already
      led to optimisation of the new SRS beamline MPW MAD 10 (see www.nwsgc.ac.uk)
      firstly involving the thinning of the beryllium windows as much as possible and
      planning for a MAR Research tilted detector 'desk top beamline' geometry. Thus
      the use of softer, i.e. 2 to 3 A wavelength range, X-rays will allow optimisation
      of xenon and iodine L-edge f " and enhancing of sulphur f " signals for higher
      throughput protein crystallography. Softer X-rays utilisation in protein
      crystallography includes work done on SRS bending-magnet station 7.2 in the early
      1980s by the author as station scientist (Helliwell, 1984). In the future
      development of XFELs these softer X-ray wavelengths could also be harnessed and
      relax the demands to some extent on the complexity and cost of an XFEL. Thus, by
      use of say 4 A XFEL radiation and use of a back-scattering geometry area detector
      the single molecule molecular transform could be sampled to a spatial resolution
      of 2 A, sufficient, in principle, for protein model refinement (Miao et al.,
      1999). Meanwhile, Miao et al. (2003) report the first experimental recording of
      the diffraction pattern from intact Escherichia coli bacteria using coherent X
      rays, with a wavelength of 2 A, at a resolution of 30 nm and a real-space image
      constructed. The new single-particle X-ray diffraction-imaging era has commenced.

PMID- 14646120
TI  - Recent developments in micro-diffraction on protein crystals.
AB  - Protein crystallography micro-diffraction and micro small-angle X-ray scattering
      at a third-generation synchrotron radiation source undulator beamline both
      require a compromise on beam size and beam divergence. Micro small-angle X-ray
      scattering requires in addition an as-close-as-possible angular approach to the
      direct beam, which is mainly limited by the beam divergence at the sample
      position. Both techniques have been developed at the ESRF microfocus beamline in
      a complimentary way. The development of a dedicated microgoniometer in the frame
      of an EMBL/ESRF collaboration has revealed the potential of micro-diffraction for
      protein crystallography and is a step in the quest for user friendly
      instrumentation.

PMID- 14646121
TI  - Synchrotron techniques for metalloproteins and human disease in post genome era.
AB  - Metalloproteins make up some 30% of proteins in known genomes. Metalloproteins
      are a special class of proteins that utilise the unique properties of metal atoms
      in conjunction with the macromolecular assembly to perform life-sustaining
      processes. A number of metalloproteins are known to be involved in many disease
      states including ageing processes. The incorporation of the metal ion is a very
      tightly regulated process that, in vivo, very often requires specific chaperones
      to deliver and help incorporate the metal atom in the macromolecule. The lack of
      or inappropriate incorporation of metals along with genetic factors can lead to
      the mis-function of these proteins leading to disease. The mis-functions due to
      genetic alterations that lead to diseases like ALS (amyotrophic lateral sclerosis
      or motor neuron disease) and Creutzfeld Jacob disease (CJD) are now well
      recognised. Synchrotron radiation sources provide a unique set of structural
      tools, which in combination can prove extremely powerful in providing a
      comprehensive picture of these complex biological systems. In particular for
      metalloproteins, the combined use of X-ray crystallography, X-ray solution
      scattering and X-ray spectroscopy (XAFS) is extremely useful. We are currently
      engaged in a structural study where our aim is to characterize structurally and
      functionally metalloproteins and then transfer this knowledge to afford the
      problem of the mis-function of metalloproteins that lead to these terminal
      illnesses, either due to a gain of function/property or a loss of
      function/property. In this context, the benefits of adopting the 'philosophy'
      being developed for the structural genomics effort are highlighted.

PMID- 14646122
TI  - Conceptual design of novel IP-conveyor-belt Weissenberg-mode data-collection
      system with multi-readers for macromolecular crystallography. A comparison
      between Galaxy and Super Galaxy.
AB  - Galaxy is a Weissenberg-type high-speed high-resolution and highly accurate fully
      automatic data-collection system using two cylindrical IP-cassettes each with a
      radius of 400 mm and a width of 450 mm. It was originally developed for static
      three-dimensional analysis using X-ray diffraction and was installed on bending
      magnet beamline BL6C at the Photon Factory. It was found, however, that Galaxy
      was also very useful for time-resolved protein crystallography on a time scale of
      minutes. This has prompted us to design a new IP-conveyor-belt Weissenberg-mode
      data-collection system called Super Galaxy for time-resolved crystallography with
      improved time and crystallographic resolution over that achievable with Galaxy.
      Super Galaxy was designed with a half-cylinder-shaped cassette with a radius of
      420 mm and a width of 690 mm. Using 1.0 A incident X-rays, these dimensions
      correspond to a maximum resolutions of 0.71 A in the vertical direction and 1.58
      A in the horizontal. Upper and lower screens can be used to set the frame size of
      the recorded image. This function is useful not only to reduce the frame exchange
      time but also to save disk space on the data server. The use of an IP-conveyor
      belt and many IP-readers make Super Galaxy well suited for time-resolved,
      monochromatic X-ray crystallography at a very intense third-generation SR
      beamline. Here, Galaxy and a conceptual design for Super Galaxy are described,
      and their suitability for use as data-collection systems for macromolecular time
      resolved monochromatic X-ray crystallography are compared.

PMID- 14646124
TI  - Macromolecular crystal growth investigations using atomic force microscopy.
AB  - Direct visualization of macromolecular crystal growth using atomic force
      microscopy (AFM) has provided a powerful tool in the delineation of mechanisms
      and the kinetics of the growth process. It has further allowed us to evaluate the
      wide variety of impurities that are incorporated into crystals of proteins,
      nucleic acids, and viruses. It is possible, using AFM, to image the defects and
      imperfections that afflict these crystals, the impurity layers that poison their
      surfaces, and the consequences of various factors on morphological development.
      All of these can be recorded under normal growth conditions, in native mother
      liquors, over time intervals ranging from minutes to days, and at the molecular
      level.

PMID- 14646123
TI  - Secure UNIX socket-based controlling system for high-throughput protein
      crystallography experiments.
AB  - A control system for high-throughput protein crystallography experiments has been
      developed based on a multilevel secure (SSL v2/v3) UNIX socket under the Linux
      operating system. Main features of protein crystallography experiments
      (purification, crystallization, loop preparation, data collecting, data
      processing) are dealt with by the software. All information necessary to perform
      protein crystallography experiments is stored (except raw X-ray data, that are
      stored in Network File Server) in a relational database (MySQL). The system
      consists of several servers and clients. TCP/IP secure UNIX sockets with four
      predefined behaviors [(a) listening to a request followed by a reply, (b) sending
      a request and waiting for a reply, (c) listening to a broadcast message, and (d)
      sending a broadcast message] support communications between all servers and
      clients allowing one to control experiments, view data, edit experimental
      conditions and perform data processing remotely. The usage of the interface
      software is well suited for developing well organized control software with a
      hierarchical structure of different software units (Gaponov et al., 1998), which
      will pass and receive different types of information. All communication is
      divided into two parts: low and top levels. Large and complicated control tasks
      are split into several smaller ones, which can be processed by control clients
      independently. For communicating with experimental equipment (beamline optical
      elements, robots, and specialized experimental equipment etc.), the STARS server,
      developed at the Photon Factory, is used (Kosuge et al., 2002). The STARS server
      allows any application with an open socket to be connected with any other clients
      that control experimental equipment. Majority of the source code is written in
      C/C++. GUI modules of the system were built mainly using Glade user interface
      builder for GTK+ and Gnome under Red Hat Linux 7.1 operating system.

PMID- 14646125
TI  - Modified microbatch and seeding in protein crystallization experiments.
AB  - The formation of nuclei in a crystallization experiment requires the interaction
      of protein molecules until a critical size of aggregate is created. In many
      crystallization screens sufficiently high levels of saturation are never reached
      to allow this critical nucleation event to occur. There are at least two
      possibilities to change this situation. The first is to increase the
      concentration of the protein and precipitating agent during the experiment to
      levels where spontaneous nucleation will occur. The second is to influence the
      nucleation event so that crystals can form at lower concentrations. The use of a
      modified microbatch method has made the first strategy possible and the use of
      heterogeneous seeding can be used to influence the second.

PMID- 14646127
TI  - Impurity effects on lysozyme crystal growth.
AB  - Atomic force microscopy (AFM) and X-ray diffraction experiments have been
      combined to study the correlation between impurity incorporation, crystal surface
      morphology and crystal quality. Hen egg-white lysozyme has been used as a model
      protein, and covalently bound lysozyme dimer as a model impurity. AFM observation
      of the [101] crystal face revealed that the crystal surface clearly became rough
      when 5% impurity was added, and the steps disappeared as the impurity
      concentration increased to 10%. The crystal quality was evaluated by four
      factors: maximum resolution limit, <I>/<sigmaI>, Rmerge, and overall B factor. In
      every index, the crystal quality tended to degrade as the impurity concentration
      increased. The B-factor dropped significantly at 5% impurity; at the same time
      the step roughening was observed. This strongly suggested that the impurity
      incorporation affected the step growth mechanism and degraded the crystal
      quality.

PMID- 14646126
TI  - Protein crystallization by using porous glass substrate.
AB  - The effects of a commercially available porous glass substrate (Corning Porous
      Glass No.7930) on the heterogeneous nucleation of proteins [hen egg-white
      lysozyme (HEWL), thaumatin and apoferritin] have been investigated in order to
      develop an improved method to facilitate the nucleation of protein crystals. It
      was found that the porous glass substrate could promote the nucleation at lower
      supersaturations. The induction time for nucleation decreased, and the crystals
      obtained from porous glass substrates were larger than those from normal glass
      substrates. Many pores and channels of 10-100 nm in diameter were observed on the
      porous glass surface by atomic force microscopy (AFM). It is believed that these
      pores and channels are crucial for facilitating the nucleation process in this
      work.

PMID- 14646128
TI  - Rapid solubility measurement of protein crystals as a function of precipitant
      concentration with micro-dialysis cell and two-beam interferometer.
AB  - A novel dialysis-based technique was developed for the rapid and sample-saving
      determination of the precipitant dependence of protein solubility. A unique thin
      dialysis cell was developed which permits both the direct optical measurement of
      protein concentration and the observation of concentration gradients around a
      crystal via two-beam interferometry. Interferograms around a lysozyme crystal
      under the desired concentrations of precipitant (NaCl) and lysozyme were observed
      to determine whether the crystal is growing or dissolving. This technique enables
      the precipitant-dependent solubility curve of lysozyme crystal to be obtained in
      two days using a small sample (total amount: 7 mg lysozyme).

PMID- 14646129
TI  - Improvement of protein crystal quality by forced flow solution.
AB  - Flow experiments in growing protein crystals were conducted to clarify the
      influence of the solution flow on the crystal quality. Lysozyme crystals grown
      under various flow velocities were analyzed by using synchrotron radiation to
      assess the quality. As a result, the crystals grown under forced flow were of
      better quality than those grown in quiescent conditions.

PMID- 14646130
TI  - Crystallization of a large single crystal of cubic insulin for neutron protein
      crystallography.
AB  - The growth of a large single crystal of cubic porcine insulin for
      characterization of hydrogen and hydration in cubic insulin crystals by neutron
      diffraction analysis is reported. Growth in D2O was investigated based on the
      phase diagram for cubic insulin to determine appropriate growth conditions, and a
      large single crystal was then successfully grown by a dialysis method to a size
      of 4.0 x 4.0 x 1.3 mm3. Neutron diffraction analysis of the cubic insulin
      crystals was carried out using a single-crystal diffractometer at the JRR-3M
      reactor of the Japan Atomic Energy Research Institute. In preliminary analysis,
      Npi appears to be protonated and Ntau deprotonated in His5 in the B-chain,
      whereas both Npi and Ntau are protonated in His10.

PMID- 14646131
TI  - A simplified counter diffusion method combined with a 1D simulation program for
      optimizing crystallization conditions.
AB  - We developed a new protein crystallization method has been developed using a
      simplified counter-diffusion method for optimizing crystallization condition. It
      is composed of only a single capillary, the gel in the silicon tube and the screw
      top test tube, which are readily available in the laboratory. The one capillary
      can continuously scan a wide range of crystallization conditions (combination of
      the concentrations of the precipitant and the protein) unless crystallization
      occurs, which means that it corresponds to many drops in the vapor-diffusion
      method. The amount of the precipitant and the protein solutions can be much less
      than in conventional methods. In this study, lysozyme and alpha-amylase were used
      as model proteins for demonstrating the efficiency of this method. In addition,
      one-dimensional (1-D) simulations of the crystal growth were performed based on
      the 1-D diffusion model. The optimized conditions can be applied to the initial
      crystallization conditions for both other counter-diffusion methods with the
      Granada Crystallization Box (GCB) and for the vapor-diffusion method after some
      modification.

PMID- 14646132
TI  - SOLVE and RESOLVE: automated structure solution, density modification and model
      building.
AB  - The software SOLVE and RESOLVE can carry out all the steps in macromolecular
      structure solution, from scaling and heavy-atom location through phasing, density
      modification and model-building in the MAD, SAD and MIR cases. SOLVE uses scoring
      scheme to convert the decision-making in macromolecular structure solution to an
      optimization problem. RESOLVE carries out the identification of NCS, density
      modification and automated model-building. The procedure is fully automated and
      can function at resolutions as low as 3 A.

PMID- 14646133
TI  - Recent developments in the PHENIX software for automated crystallographic
      structure determination.
AB  - A new software system called PHENIX (Python-based Hierarchical ENvironment for
      Integrated Xtallography) is being developed for the automation of
      crystallographic structure solution. This will provide the necessary algorithms
      to proceed from reduced intensity data to a refined molecular model, and
      facilitate structure solution for both the novice and expert crystallographer.
      Here, the features of PHENIXare reviewed and the recent advances in
      infrastructure and algorithms are briefly described.

PMID- 14646134
TI  - Breaking good resolutions with ARP/wARP.
AB  - New procedures are outlined that enable ARP/wARP to automatically build protein
      models with diffraction data extending to about 2.5 A. An overview of ongoing
      research is given and possible future advances are discussed.

PMID- 14646135
TI  - Scaling of one-shot oscillation images with a reference data set.
AB  - By combining a least-squares procedure with the program MOSFLM, a program SCLONE
      has been developed which processes diffraction images that do not contain serial
      oscillation images and may have a few or no full reflections. After each image
      was processed by MOSFLM, the partialities and structure amplitudes of the
      reflections were estimated using a least-squares method to refine the scaling
      factor, the relative temperature factor, the mosaic spread, cell constants, and
      missetting angles for each independent image. The SCLONE calculation
      significantly improved the quality of the intensities from the reflections
      obtained by the initial MOSFLM calculation and crystal structural refinement
      confirmed the improvement. The SCLONE calculation indicated that the reflection
      of the present crystal had a rocking curve that was steeper at the middle of the
      profile and more gradual at both ends of the profile than that assumed in the
      program MOSFLM.

PMID- 14646136
TI  - Applications of ACORN to data at 1.45 A resolution.
AB  - One of the main interests in the molecular biosciences is in understanding
      structure-function relations and X-ray crystallography plays a major role in
      this. ACORN can be used as a comprehensive and efficient phasing procedure for
      the determination of protein structures when atomic resolution data are
      available. An initial model can automatically be built by ARP/wARP followed by
      REFMAC for refinement. The alpha helices and beta sheets occurring in many
      protein structures can be taken as starting fragments for structure solution in
      ACORN. ACORN, along with ARP/wARP followed by REFMAC, can be an ab initio method
      for solving protein structure for which data are better than 1.2 A (atomic
      resolution). Attempts are here made in extending its applications to real data at
      1.45 A resolution and also to truncated data at 1.6 A resolution. Two previously
      known structures, congerin II and alkaline cellulase N257, were resolved using
      the above approach. Automatic structure solution, phasing and refinement for real
      data at still lower resolutions for proteins of various complexities are being
      carried out. Data mining of the secondary structural features using PDB is being
      carried out for this new approach for 'seed-phasing' to ACORN.

PMID- 14646137
TI  - A new neutron single-crystal diffractometer dedicated for biological
      macromolecules (BIX-4).
AB  - A new neutron single-crystal diffractometer (BIX-4) has been constructed at 1G-B
      port of JRR-3M in JAERI. Since at 1G-B port another diffractometer for biology,
      BIX-3, and a high-resolution powder diffractometer (HRPD) coexist, the
      monochromator house needed to be reconstructed. The main architecture of BIX-4 is
      based on that of BIX-3. BIX-4 uses an elastically-bent perfect-Si crystal
      monochromator and neutron imaging plates as BIX-3. In addition, several
      optimizations of the monochromator and modifications from previous BIX-3 are
      carried out. The final gain of the neutron intensity at the detector position is
      estimated to be 2.5 times larger than previous BIX-3. That higher performance
      increases the opportunities to apply neutron crystallography to biological
      macromolecules which give only weak reflections and/or small crystals.

PMID- 14646138
TI  - Hydration structures in proteins and neutron diffraction experiment on
      dissimilatory sul te reductase D (DsrD).
AB  - Neutron crystallography can provide a substantial amount of information about the
      hydration of proteins. The hydration patterns of three proteins, whose structures
      have been solved at 1.5 or 1.6 A resolution using our BIX-type diffractometers,
      show interesting features. The water molecules adopt a variety of shapes in the
      neutron Fourier maps, revealing details of intermolecular hydrogen-bond formation
      and dynamics of hydration. In addition, the neutron diffraction study of a DNA
      binding protein, dissimilatory sulfite reductase D (DsrD) is briefly described,
      and some preliminary results are presented. This topic is of interest because it
      is well known that hydrogen bonds play important roles in DNA-protein
      recognition.

PMID- 14646139
TI  - Neutron diffraction studies on rubredoxin from Pyrococcus furiosus.
AB  - Single-crystal neutron diffraction data up to a resolution of 1.5 A have been
      collected at room temperature on two forms of rubredoxin using the BIX-3
      diffractometer at the JRR-3 reactor of the Japan Atomic Energy Research Institute
      (JAERI). Rubredoxin is a small iron-sulfur redox protein with 53 amino acid
      residues, and the source of this particular protein is the hyperthermophile
      Pyrococcus furiosus, a microorganism that normally lives at temperatures near
      that of boiling water. Data were collected on crystals of the wild-type protein
      and on a mutant in which three of the residues have been replaced. In this paper
      we will be describing several sets of results arising from these high-resolution
      neutron structure determinations: (a) the H/D exchange pattern of the N-H bonds
      of the main backbone, which give information about which regions of the molecule
      are more exposed to solvent; (b) the orientations of some of the O-D bonds in the
      protein, information which is often not obtainable from X-ray results; (c) the
      structure and appearance of water molecules in the protein crystals; and (d) some
      structural features which may help rationalize the remarkable thermal stability
      of the wild-type protein from this intriguing microorganism

PMID- 14646140
TI  - Protein crystallography with spallation neutrons.
AB  - Spallation neutrons are ideal for diffraction studies of proteins and oriented
      molecular complexes. With spallation neutrons and their time-dependent wavelength
      structure, one can select data with an optimal wavelength band and cover the
      whole Laue spectrum as time (wavelength) resolved diffraction data. This
      optimises data quality with best peak to background ratios and provides spatial
      and energy resolution to eliminate peak overlaps. Such a Protein Crystallography
      Station (PCS) has been built and tested at Los Alamos Neutron Science Centre. A
      partially coupled moderator is used to increase flux and data are collected by a
      cylindrical He3 detector covering 120 degrees with 200 mm height. The PCS is
      described along with some examples of data collected from proteins.

PMID- 14646141
TI  - Rapid routine structure determination of macromolecular assemblies using electron
      microscopy: current progress and further challenges.
AB  - Although the methodology of molecular microscopy has enormous potential, it is
      time consuming and labor intensive. The techniques required to produce a three
      dimensional (3D) electron density map of a macromolecular structure normally
      require manual operation of an electron microscope by a skilled operator and
      manual supervision of the sometimes complex software needed for analysis and
      calculation of 3D maps. Systems to automate the process of data acquisition from
      an electron microscope are being developing and these systems are being
      integrated with specimen handling operations and post acquisition data
      processing. Here, the current performance of our existing systems and the future
      challenges involved in substantially improving both the sustained throughput and
      the yield of automated data collection and analysis are reported.

PMID- 14646142
TI  - Water and glycerol permeation through the glycerol channel GlpF and the aquaporin
      family.
AB  - The 2.2 A resolution crystal structure of GlpF, an E. coli aquaporin that
      facilitates the flow of glycerol, water and other small solutes, provides much
      insight into the molecular function and selectivity of aquaporins. Using GlpF and
      its atomic structure as a paradigm for the ten highly conserved human aquaporins,
      site-directed mutagenesis has been used to mutate residues that are possibly
      integral to the structure and function of different aquaporins. X-ray
      crystallography and other biophysical and molecular simulation methods allows for
      assessment of these changes at the structural and functional level. Initial
      attempts to convert the glycerol specific properties of GlpF towards a water
      specific aquaporin resulted in the shifting of GlpF channel properties towards
      that of the water aquaporins. This result reveals the great possibility of
      emulating and deciphering the function of other aquaporins with GlpF via
      mutagenesis and investigation of structure and function.

PMID- 14646143
TI  - Virus structure analysis with synchrotron radiation: methods and results.
AB  - Structural studies of viruses that are investigated as part of a program to
      understand molecular machines are described. Crystallography, solution X-ray
      scattering, electron microscopy and molecular virology were employed to
      investigate structure, assembly and maturation of RNA and dsDNA viruses. 240
      copies of the RNA viral subunits (each with 650 amino acids) spontaneously
      assemble at pH 7 in a baculovirus expression system to form T = 4 icosahedral
      particles, 450 A in diameter. At pH 5 the particles condense to 410 A and the
      subunits auto-catalytically cleave at residue 570. 420 copies of the dsDNA viral
      subunits (281 amino acids each) assemble in an E. coli expression system to form
      T = 7 icosahedral particles, 450 A in diameter. At pH 4 the particles expand to
      650 A diameter with the auto-catalytic formation of cross links between a lysine
      side chain and an asparagine side chain creating a concatenated set of 60 hexamer
      and 12 pentamer rings rendering the particle impervious to denaturation without
      protease treatment. Moderate- to high-resolution structures of the procapsids and
      capsids of these virus particles have been determined as well as cryoEM
      reconstructions of intermediate structures in order to define the driving force
      and the trajectories of these large-scale transitions.

PMID- 14646144
TI  - RNA recognition and base flipping by the toxin sarcin.
AB  - Sarcin is a member of a fungal toxin family that enters cells and specifically
      cleaves one of the thousands of RNA phosphodiester bonds in the ribosome. As a
      result, elongation factor binding is disrupted, translation is inhibited and
      apoptosis is triggered. The toxin targets a universal RNA structure in the
      ribosome called the sarcin/ricin loop (SRL). A 1.11 A resolution structure of a
      minimal SRL RNA substrate (approximately 30-mer) shows that the loop portion of
      the substrate folds into two common building blocks of RNA structure: a bulged-G
      motif (recognition site) and a GAGA tetraloop (cleavage site). To elucidate the
      structural basis of toxin action, we determined two co-crystal structures of the
      sarcin homologue restrictocin bound to different analogs of a minimal SRL RNA
      substrate. Our studies argue that site selection by the toxin depends on direct
      base and shape recognition of the SRL RNA, and that cleavage by the toxin depends
      on a base flipping mechanism that positions the nucleophile for in-line attack on
      the scissile bond.

PMID- 14646145
TI  - Leveraging structural approaches: applications of NMR-based screening and X-ray
      crystallography for inhibitor design.
AB  - In the last several years, NMR strategies in drug discovery have evolved from a
      primarily structural focus to a set of technologies that are non-structural in
      nature but that have a much greater impact on the identification and optimization
      of real drug leads. NMR-based screening methods, such as the SHAPES strategy,
      help rapidly identify good starting points for drug design in a relatively high
      throughput implementation. The SHAPES method uses simple NMR techniques to detect
      binding of a limited, but diverse library of low molecular weight, soluble
      compounds to a potential drug target. SHAPES library compounds are derived
      largely from molecular frameworks most commonly found in known therapeutic
      agents. The NMR experiments used in these protocols are based on the well-known
      NMR techniques, and may be applied to targets with no limitation on molecular
      weight and no requirement for isotope labeling. Following screening, SHAPES hits
      may be used to guide virtual screening, synthesis of combinatorial libraries, and
      bias the first compounds that undergo high throughput screening. Integration of
      the SHAPES strategy with iterative X-ray crystallographic structure determination
      can be very useful in deriving an initial structural pharmacophore model and
      achieving significant in vitro potency in a short time frame. Here, examples are
      provided of how the combination of NMR SHAPES screening, virtual screening,
      molecular modeling and X-ray crystallography has led to novel drug scaffolds in
      several drug discovery programs: JNK3 MAP kinase and the fatty acid binding
      protein, aP2.

PMID- 14646146
TI  - Crystal structure of the complex of porcine pancreatic elastase with TEI-8362.
AB  - The crystal structure of porcine pancreatic elastase (PPE) complexed with a new
      benzoxazinone inhibitor, TEI-8362, of human neutrophil elastase (HNE) was
      determined at 1.8 A resolution. The hydroxyl oxygen of Ser195 opened the
      benzoxazinone by nucleophilic attack and formed a covalent bond with the carbonyl
      carbon. Hydrophobic interaction between the terminal benzene of TEI-8362 and the
      S4 pocket is reinforced by the side chain of Arg217 and has an impact on the
      ligand binding conformation. Two additional interactions with the oxyanion hole
      and His57 are introduced to the benzoxazinone structure of TEI-8362. These
      combinatorial interactions will also exist in HNE and cause high preference of
      TEI-8362 for HNE.

PMID- 14646147
TI  - Crystal structure of a humanized Fab fragment of anti-tissue-factor antibody in
      complex with tissue factor.
AB  - Tissue factor (TF) is a membrane-anchored protein that initiates the extrinsic
      cascade of blood coagulation. TF forms a complex with serine protease Factor
      VIIa, and then activates Factor X zymogen to Factor Xa, leading to the blood
      coagulation. Humanized anti-TF antibody hATR-5 strongly inhibits TF-initiated
      blood coagulation, and is of potential use for various thrombotic diseases. The
      Fab fragment of antibody hATR-5 is obtained for crystallization. The crystal
      structure of the complex of the Fab with extracellular domains of human TF was
      determined with the molecular replacement method, and refined to an R factor of
      0.196 at 2.1 A resolution. All the complementarity-determining regions (CDRs) of
      the Fab are involved in interaction with the C-terminal-side extracellular domain
      of TF through 19 hydrogen bonds. The interface between the Fab and TF molecules
      contains 15 water molecules, and yields buried surface areas as wide as 2000 A2.
      The TF surface in the interface is possibly involved in the activation of Factor
      X, by forming a transient ternary complex of Factor X-TF-Factor VIIa.
      Electrostatic interactions are predominantly observed between the heavy-chain
      CDRs and TF. These hydrogen-bonding and electrostatic interactions together with
      the wide buried areas contribute to the high affinity of the antibody toward TF,
      leading to the effective inhibition of the TF-initiated blood coagulation.

PMID- 14646148
TI  - Protein splicing of yeast VMA1-derived endonuclease via thiazolidine
      intermediates.
AB  - Protein splicing precisely excises out an internal intein segment from a protein
      precursor, and concomitantly ligates the N- and C-terminal extein polypeptides
      flanking the intein. A recombinant X10SNS bearing N- and C-extein polypeptides
      has been prepared for the intein endonuclease derived from the Saccharomyces
      cerevisiae VMA1 gene. X10SNS has replacements of C284S, H362N and C738S, and
      forms the intein and extein segments in the crystal lattice. The crystal
      structure of X10SNS revealed a linkage between the N- and C-extein segments, and
      showed that the C284 amino group of the resultant intein segment is in
      interaction with the G283 O atom of the N-extein segment. A mechanism for the
      final S --> N acyl shift step proposes that a tetrahedral intermediate involves a
      five-membered thiazolidine ring at G283-C738 junction. An oxyanion of the
      thiazolidine intermediate is to be stabilized by the C284 N atom.

PMID- 14646149
TI  - X-ray induced reduction of the crystal of high-molecular-weight cytochrome c
      revealed by microspectrophotometry.
AB  - The crystal structures of high-molecular-weight cytochrome c (HMC) from
      Desulfovibrio vulgaris Hildenborough in the transient and reduced states have
      been determined at 2.8 A resolution. An absorption spectrum measured with
      microspectrophotometer indicated that about 86% of the hemes were reduced after
      45 min irradiation of the X-ray beam. Further exposure for 90 min did not
      significantly change the spectrum. These results suggest that HMC in the
      crystalline state is easily reduced by illumination of the X-ray beam from
      synchrotron radiation.

PMID- 14646150
TI  - X-ray analyses of d(GCGAXAGC) containing G and T at X: the base-intercalated
      duplex is still stable even in point mutants at the fifth residue.
AB  - DNA fragments containing the sequence d(GCGAAAGC) prefer to adopt a base
      intercalated (zipper-like) duplex in the crystalline state. To investigate
      effects of point mutation at the 5th residue on the structure, two crystal
      structures of d(GCGAGAGC) and d(GCGATAGC) have been determined by X-ray
      crystallography. In the respective crystals, the two octamers related by a
      crystallographic two-fold symmetry are aligned in an anti-parallel fashion and
      associated to each other to form a duplex, suggesting that the base-intercalated
      duplex is stable even when the 5th residue is mutated with other bases. The
      sheared G3:A6 pair formation makes the two phosphate backbones closer and
      facilitates formation of the A-X*-X-A* base-intercalated motif. The three
      duplexes are assembled around the three-fold axis, and their 3rd and 4th residues
      are bound to the hexamine cobalt chloride. The central 5th residues are bound to
      another cation.

PMID- 14646151
TI  - Protein crystal growth with a two-liquid system and stirring solution.
AB  - We developed two novel methods for growing large, high-quality protein crystals.
      A two-liquid system enables the convenient extraction of protein crystals without
      causing mechanical damage due to growth at the interface between two liquids.
      Since this system does not require limitations on solution volume, it is also
      suitable for the seed technique, and for growing large crystals. Another new
      concept is the mild stirring of the solution using the Floating And Stirring
      Technique (FAST) and the Micro-stirring technique. When compared to conventional
      techniques, both techniques result in a reduced number of crystals, as well as
      the growth of large crystals.

PMID- 14646155
TI  - Anti-myeloperoxidase antibodies in patients with microscopic polyangiitis.
AB  - BACKGROUND & OBJECTIVES: Anti-neutrophil cytoplasmic antibodies in active
      necrotizing and crescentic glomerulonephritis are associated with systemic
      vasculitides like Wegener's granulomatosis, Microscopic polyangitiis and Churg
      Strauss Syndrome. This study shows the incidence of ANCA with specificities to
      Myeloperoxidase and Proteinase3 in MPA cases and gives the correlation of ANCA
      with Birmingham Vasculitis Activity Score. MATERIAL & METHODS: Eighteen cases of
      MPA were diagnosed as per Chapel Hill Consensus Criteria. ANCA was detected by
      indirect immunofluorescence microscopy using fluorescence and Confocal Laser
      Scanning Microscopes. Anti-MPO and anti-PR3 were identified by commercial ELISAs
      and anti-MPO subclass and IgG isotypes were also detected. RESULTS: MPA patients
      showed a male preponderance with BVAS ranging from 17-30. Systemic involvement
      was seen in 88.9%, lower respiratory tract involvement in 77.8% and upper
      respiratory tract in only 33.3% cases. All these patients had perinuclear pattern
      on IIF, where titers ranged from 80-640 and ELISA showed anti-MPO; values ranging
      from 20-80 units/ml. IIF and ELISA showed a good correlation (r=0.77). Two
      patients having FPGN had dual specificities and had both anti-MPO and anti-PR3
      which could be picked up only by ELISA. A good correlation (r=0.78) was observed
      between BVAS and ANCA levels as well. IgG ANCA was detected in 88.7% and 11.1%
      had IgG+IgM and IgG1+IgG4 ANCA was detected in 50% patients. CONCLUSION: p-ANCA
      with anti-MPO is highly specific for MPA; both IIF and ELISA should be carried
      out for true positivity and to identify rare cases of dual specificities.
      Confocal laser scanning microscopy is useful in identifying ANCA patterns
      especially when ANA is also positive. ANCA testing with BVAS assessment will
      surely help in early diagnosis and estimating the severity of this life
      threatening disease.

PMID- 14646156
TI  - Effect of acute noise stress on acetylcholinesterase activity in discrete areas
      of rat brain.
AB  - Effect of various stressor agents on the adrenergic system in brain had been
      studied extensively. However, reports on the effect of stress on various
      parameters of central cholinergic system are scanty. And very little is known
      about the effect of noise stress on the cholinergic system in brain. Hence, it
      was decided to elucidate the effect of acute noise stress on the activity of the
      enzyme acetylcholinesterase in discrete areas of brain in albino rats. Male
      albino rats of Wistar strain were subjected to acute noise stress for 30 minutes.
      The noise of pure sine wave tone was produced by using a function generator and
      was amplified. The frequency of noise generated was 1 kHz and the intensity was
      set at 100 dB. The total acetylcholinesterase activity was determined in the
      tissues of cerebral cortex, corpus striatum, hypothalamus and hippocampus of
      brain in these rats. The enzyme activity was estimated by colorimetric method
      using acetylthiocholine iodide as the substrate. The values were compared with
      the enzyme activity in the control rats. The activity of the enzyme increased
      significantly in all the four regions of the brain in rats after exposure to
      noise stress for 30 minutes. The results of the study indicate that the exposure
      to acute noise stress could modulate the cholinergic system in these areas of
      brain in rat.

PMID- 14646157
TI  - A randomized controlled comparison of minialpartomy and lapartomy in ectopic
      pregnancy cases.
AB  - BACKGROUND: As ectopic pregnancy is associated with significant maternal
      mortality and morbidity it may be worthwhile to find alternative surgical method
      to traditional laparotomy. AIMS: To compare the efficacy, safety and cost
      effectiveness of minilaparotomy surgery for ectopic pregnancy cases with standard
      laparotomy method. SETTING AND DESIGN: A total of 60 patients of ectopic
      pregnancy were randomized for minilaparotomy and laparotomy (30 cases each) for
      three years from January. 1998 to March 2001 in a medical college hospital.
      MATERIAL AND METHODS: Patients history, clinical examination, intraoperative,
      preoperative and postoperative data were recorded and compared in minilaparotomy
      and laparotomy groups. STATISTICAL ANALYSIS USED: Chi-square and Fischer chi
      square test is used using P value of less than 0.05 as level of significance.
      RESULTS: Mean operative time was significantly less in minilaparotomy (38
      minutes) than in laparotomy group (54 minutes). Postoperative complications were
      fever in 4(13.33%) and 6(20%) cases, paralytic ileus in 3(10%) and 8(26.66%)
      cases, urinary tract infection in 2(6.66%) and 3(10%) cases and wound infection
      in 1(3.33%) and 5(16.66%) cases respectively in the two groups and were
      significantly less in the minilaparotomy cases. Mean day of mobility, starting
      normal diet and discharge from the hospital were 10 hours and 24 hours, 1.5 days
      and 3.1 days and 3.4 days and 6.9 days respectively in the two groups and were
      significantly less in the minilaparotomy group than the laparotomy group.
      CONCLUSIONS: Surgery by minilaparotomy technique in ectopic pregnancy cases
      appears to be a safe and feasible method and is superior to conventional
      laparotomy as there are minimum perioperative and postoperative complications and
      patients can be discharged early from the hospital without the need of expensive
      equipment.

PMID- 14646158
TI  - Successful pregnancy outcome after cesarean section in a case of gravid uterus
      growing in an incisional hernia of the anterior abdominal wall.
AB  - We herein report a case of a pregnant woman with previous cesarean section whose
      uterus herniated in an incisional hernia of the anterior abdominal wall at 34
      weeks of pregnancy. Incarceration of the pregnant uterus in an incisional hernia
      is a rare but serious obstetric situation. Treatment is conservative till term
      followed by delivery and herniorrhaphy as was done in our case and it was
      associated with successful outcome.

PMID- 14646159
TI  - Autoimmune hemolytic anemia associated with benign ovarian cyst: a case report
      and review of literature.
AB  - A 28-years-old female presented with severe autoimmune hemolytic anemia (AIHA),
      warm antibody mediated, and right side tubo-ovarian (TO) mass. There was sub
      optimal response to immunosuppressive therapy (IST). Eight months later she
      underwent ovarian cystectomy which resulted in complete remission of AIHA without
      the need for IST. Pathological examination of the TO mass revealed benign ovarian
      cyst. Our case highlights the need to search for ovarian cyst/mass in females
      presenting with AIHA. Since immunosuppressive therapy is usually ineffectual in
      AIHA associated with ovarian cyst, it may be appropriate to contemplate surgery
      before embarking on IST in such cases.

PMID- 14646160
TI  - Facial and body blood contamination in minor obstetrics and gynecologic
      surgeries.

PMID- 14646161
TI  - Topiramate induced somnabulism and automatic behaviour.

PMID- 14646162
TI  - Viral hepatitis (Part-IV).

PMID- 14646163
TI  - Glycosylation in congenital muscular dystrophies.
AB  - Mammalian cells produce many glycoproteins, i.e., proteins with covalently
      attached sugar chains. Recent advances in glycobiology have revealed the
      importance of sugar chains as biosignals for multi-cellular organisms including
      cell-cell communication, intracellular signaling, protein folding, and targeting
      of proteins within cells. The O-mannosyl linkage, which used to be considered
      specific to yeast, has recently been found in mammals. One of the best known O
      mannosyl-modified glycoproteins is alpha-dystroglycan, which is a central
      component of the dystrophin-glycoprotein complex isolated from skeletal muscle
      membranes. We have identified and characterized a glycosyltransferase, UDP-N
      acetylglucosamine: protein O-mannose beta1,2-N-acetylglucosaminyltransferase
      (POMGnT1), involved in the biosynthesis of O-mannosyl glycans. We subsequently
      found that loss of function of the POMGnT1 gene is responsible for muscle-eye
      brain disease (MEB). MEB is an autosomal recessive disorder characterized by
      congenital muscular dystrophy, ocular abnormalities and brain malformation (type
      II lissencephaly). Moreover, recent data suggest that aberrant protein
      glycosylation of alpha-dystroglycan is the primary cause of some forms of
      congenital muscular dystrophy. Here we review new insights into the glycobiology
      of muscular dystrophy and neuronal migration disorder.

PMID- 14646164
TI  - Conformational change of glyceraldehyde-3-phosphate dehydrogenase induced by
      acetylleucine chloromethyl ketone is followed by unique enzymatic degradation.
AB  - We have previously reported that acetylleucine chloromethyl ketone (ALCK), an
      inhibitor of acylpeptidehydrolase, induces the inhibition and degradation of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the U937 cell extract. In the
      present study, the process of ALCK-induced GAPDH degradation was investigated. A
      kinetic study revealed that GAPDH was irreversibly inhibited by ALCK. ALCK
      treatment induced a change in the signal intensity of GAPDH in the near-UV region
      of the circular dichroism (CD) spectrum, and the fluorescence intensity of GAPDH
      at 330 nm increased to about 10% when excited at 280 nm, suggesting that a
      significant conformational change of GAPDH was induced by ALCK. When the U937
      cell extract was incubated with ALCK and the products were separated by SDS
      polyacrylamide gel electrophoresis (PAGE), a 23-kDa fragment from GAPDH was
      detected by Western blotting using anti-GAPDH serum. When ALCK-treated GAPDH was
      incubated with protease fractions from the U937 cell extract, a 17-kDa fragment
      was also detected. Sequence analysis showed that the N-terminal amino acid
      sequence of the 23-kDa fragment was GKVKVG and that of 17-kDa fragment was
      RDGRGAL. Therefore, ALCK-modified GAPDH is deduced to be digested at the peptide
      bond Trp(195)-Arg(196). The protease activity liberating a 23-kDa fragment from
      ALCK-treated GAPDH was effective under the basic condition. Results suggested
      that ALCK binds to GAPDH to modulate the conformation of enzyme, which is
      susceptible to chymotrypsin-like protease activity.

PMID- 14646165
TI  - Increase in molecular rigidity of the protein conformation of brain Na+-K+-ATPase
      by modification with 4-hydroxy-2-nonenal.
AB  - The effect of lipid peroxidation product 4-hydroxy-2-nonenal (HNE) on the protein
      conformation of porcine cerebral cortex Na(+)-K(+)-ATPase was examined in term of
      the intrinsic tryptophanyl fluorescence measurement. Treatment of ATPase with HNE
      resulted in a decrease in the fluorescence intensity and an increase in the
      fluorescence anisotropy in a concentration-dependent manner. The difference in
      the fluorescence intensity and fluorescence anisotropy observed between the
      control and HNE-modified ATPase completely disappeared after treatment of the
      protein with guanidine hydrochloride (1 M). These results suggest that HNE
      modification of the Na(+)-K(+)-ATPase induces alterations in the conformation of
      the enzyme molecule. This interpretation was further supported by a decrease in
      fluorescence quenching efficiency with acrylamide and sulfhydryl (SH) content.
      The decrease in quenching efficiency suggests that the proximity of the quencher
      molecule to the fluorophores located in the enzyme is suppressed. Modification of
      the enzyme with N-ethylmaleimide (NEM) also resulted in a decrease in quenching
      efficiency with the loss of SH groups. Furthermore, a good relationship between
      the SH content and these fluorescence parameters (fluorescence anisotropy and
      quenching efficiency) were observed. On the other hand, treatment of the Na(+)
      K(+)-ATPase with other aldehydes such as malondialdehyde (MDA), 1-hexanal and
      nonanal did not affect either the quenching efficiency or SH content. Based on
      these results, the possibility of alterations in the physical properties of the
      Na(+)-K(+)-ATPase associated with modification by HNE has been discussed.

PMID- 14646166
TI  - 1,3-selenazol-4-one derivatives inhibit inducible nitric oxide-mediated nitric
      oxide production in lipopolysaccharide-induced BV-2 cells.
AB  - Activated microglia extensively produce nitric oxide (NO) by inducing expression
      of inducible NO synthase (iNOS). NO plays a deleterious role in brain
      inflammation and neuronal death. In the present study, we investigated the
      effects of 1,3-selenazol-4-one derivatives (Sz-A, B, C, D and E) on NO production
      and iNOS expression in lipopolysaccharide (LPS)-induced BV-2 cells, a murine
      microglia cell line. Among these compounds, Sz-B and C remarkably inhibited LPS
      induced NO production relative to that of Sz-A, D, and E at 5 microM in BV-2
      cells. Sz-B and C dose-dependently inhibited NO production at 1, 5, and 10 microM
      without toxicity to BV-2 cells. Sz-B and C also dose-dependently suppressed iNOS
      expression at the same concentrations in LPS-induced BV-2 cells. This result
      suggests that Sz-B and C inhibit iNOS-mediated NO production in LPS-induced BV-2
      cells. Structurally, Sz-B and C bear an ethyl or methyl group at the 5 positions
      of the 4-selenazolone skeletons, which could play an important role in inhibiting
      iNOS-mediated NO production.

PMID- 14646167
TI  - Cardiovascular assessment of ER-118585, a selective phosphodiesterase 5
      inhibitor.
AB  - The aim of this study was to assess the cardiovascular effects of a selective
      phosphodiesterase 5 inhibitor ER-118585, 4-[(3-chloro-4-methoxybenzyl)amino]-1-(2
      hydroxy-7-azaspiro[3.5]non-7-yl)-6-phthalazinecarbonitrile monohydrochloride. The
      present results indicated that 1) ER-118585 significantly inhibited the human
      ether-a-go-go related gene (HERG) tail current at 10 nM and above with an IC(50)
      value of 40.7 nM in human embryonic kidney 293 cells transfected with HERG cDNA;
      2) ER-118585 at 100 and 1000 nM significantly increased the action potential
      duration (APD) at 50% and 90% repolarization in isolated papillary muscles of
      guinea pig; and 3) intravenous infusion of ER-118585 at 10 microg/kg/min
      significantly prolonged the QT interval by 10.5+/-1.6% from 281+/-2 ms to 311+/-6
      ms in six anesthetized dogs subjected to atrial pacing. In consideration of both
      the plasma concentration of ER-118585 (984+/-78 nM, n=3) and its protein binding
      fraction (99.0+/-0.1%, n=5), the free plasma concentration was estimated at 9.8+/
      0.8 nM, which is consistent with the minimum concentration of HERG current
      inhibition. In conclusion, these evaluation methods demonstrated that ER-118585
      could prolong the QT interval via APD prolongation, attributable to the
      inhibition of the HERG potassium current.

PMID- 14646168
TI  - Protective effect of aqueous extract of Ginseng radix against 1-methyl-4
      phenylpyridinium-induced apoptosis in PC12 cells.
AB  - Ginseng radix, the root of Panax ginseng C. A. MEYER (Araliaceae), is one of the
      best-known Oriental medicinal herbs with numerous therapeutic applications. To
      investigate whether Ginseng radix possesses a protective effect against 1-methyl
      4-phenylpyridine (MPP(+))-induced cytotoxicity in neuronal cells, 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow
      cytometry, DNA fragmentation assay, reverse transcription-polymerase chain
      reaction (RT-PCR), Western blotting, and caspase-3 enzyme assay were performed on
      PC12 neuronal cells. Cells treated with MPP(+) exhibited various apoptotic
      features, while cell pretreated with Ginseng radix prior to MPP(+) exposure
      showed a decrease in the occurrence of apoptotic features. These results suggest
      that Ginseng radix may exert a protective effect against MPP(+)-induced apoptosis
      in PC12 cells.

PMID- 14646169
TI  - Hypotensive activity of the ethanol extract of Pavetta crassipes leaves.
AB  - Pavetta crassipes leaf is routinely used locally in Nigeria for the management of
      respiratory disorders and hypertension. The hypotensive and other cardiovascular
      effects of Pavetta crassipes were investigated in cats and rats. The effects of
      the extract on rat and cat blood pressures, isolated rat atria, rat portal vein,
      isolated rat aorta and rat vas deferens were studied. Specific receptor
      antagonists (atropine, mepyramine, phentolamine, propranolol) were used to
      elucidate the underlying mechanism(s) involved in the cardiovascular changes
      induced by P. crassipes. The results revealed that the ethanolic extract of
      Pavetta crassipes lowered the blood pressures of cats and rats in a dose
      dependent manner. The extract also caused a concentration-dependent decrease in
      the force of contraction of the isolated rat atria and rat portal vein. The
      decreases in blood pressure values were attenuated in the presence of a beta
      adrenoceptor antagonist, propranolol. The extract also attenuated isoprenaline
      induced contraction of the rat atria. However, the extract did not affect
      contractions evoked by KCl, norepinephrine and 5-HT on the rat aorta. Pavetta
      crassipes contains biologically active substances that may be useful in the
      management of hypertension.

PMID- 14646170
TI  - Effects of atorvastatin and pravastatin on glucose tolerance in diabetic rats
      mildly induced by streptozotocin.
AB  - Effects of atorvastatin and pravastatin on glucose tolerance in mildly induced
      diabetic rats by streptozotocin at 24 mg/kg, i.v. were studied. Non-diabetic and
      diabetic rats were given orally 0.5% carboxymethylcellulose (control), 8 mg/kg
      atorvastatin or 8 mg/kg pravastatin once a day for 6 weeks. An oral glucose
      tolerance test (OGTT) was carried out 1, 2, 3, and 6 weeks after the
      administration. The blood glucose and plasma insulin levels measured before OGTT
      in the diabetic rats were not different from those in the non-diabetic rats.
      However, the hyperglycemic response to OGTT in the diabetic rats significantly
      exceeded that in the non-diabetic rats. The plasma insulin increased by OGTT in
      the diabetic rats appeared to be lower than that in the non-diabetic rats. Statin
      treatments for 1 week did not modify the OGTT-induced hyperglycemia appreciably,
      although there were some significant differences. More than 2 weeks after
      administration, the blood glucose levels at several time points after a glucose
      intake in the atorvastatin-treated diabetic rats were significantly higher than
      the respective levels in the control diabetic rats. Neither atorvastatin nor
      pravastatin modified the OGTT-induced insulin secretion. Statins, especially
      atorvastatin, may influence the glucose tolerance in mildly induced diabetic rats
      without alterations of insulin secretion.

PMID- 14646171
TI  - Inhibition of syk activity and degranulation of human mast cells by flavonoids.
AB  - To investigate the effect of flavonoids on the activation of p72(syk) (Syk)
      protein tyrosine kinase which plays a pivotal role in the high affinity IgE
      receptor-mediated degranulation of mast cells, we picked out 10 flavonoids,
      classified them into 4 series, and examined their effects on the activation of
      Syk and on the degranulation of human mast cells. Flavones and flavonols showed
      clear inhibition, whereas flavanones and isoflavones had either weak or no effect
      on Syk enzymatic activity induced by amino acid peptide corresponding to the
      activation loop domain and on IgE-dependent degranulation of human cultured mast
      cells (HCMC). On the basis of calculated logP (ClogP) values as a prediction of
      compound lipophilicity, some flavonoids were speculated to have low
      lipophilicity, the reason for poor cell permeability. A significant relationship
      was observed between the inhibition of Syk activity and HCMC degranulation
      attributable to flavonoids when the ClogP values of the compounds were taken into
      account (r(2)=0.89). These results suggested that the impairment of mast cell
      degranulation by several flavonoids classified into flavones and flavonols might
      be mediated via inhibition of the intracellular activation of Syk.

PMID- 14646172
TI  - New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor
      agonistic activity as potent ocular-hypotensive agents.
AB  - To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive
      effects with minimal side effects, we evaluated the agonistic activities of newly
      synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor
      both in vitro and in vivo. The iris constrictions induced by the derivatives and
      their effects on melanin content were examined using cat isolated iris sphincters
      and cultured B16 melanoma cells, respectively. The effects of derivative ester
      forms on miosis and intraocular pressure (IOP) were evaluated in cats and
      cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds
      were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a
      carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost
      (100 microM) significantly increased the melanin content of cultured B16 melanoma
      cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not.
      Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and
      ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently
      than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005%
      latanoprost (for at least 8 h). These findings indicate that 15,15
      difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent
      prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may
      be worthy of further evaluation as an ocular-hypotensive agent.

PMID- 14646173
TI  - Multiple cedar pollen challenge diminishes involvement of histamine in allergic
      conjunctivitis of Guinea pigs.
AB  - It has been reported that antihistamines do not fully modify symptoms of allergic
      conjunctivitis in clinical settings, suggesting that histamine is not the only
      contributor to symptom generation in the disease. However, in the majority of
      experimental allergic conjunctivitis models, antihistamines are very effective in
      the reduction of symptoms. In the present study, we used our recently developed
      guinea pig model of allergic conjunctivitis and evaluated whether involvement of
      histamine in the induction of symptoms of allergic conjunctivitis is altered by
      multiple antigen challenges. Guinea pigs were sensitized by intraperitoneal
      injection of Japanese cedar pollen extracts adsorbed on aluminum hydroxide gel,
      and then challenged by dropping a pollen suspension without the adjuvant on each
      eye once a week until the 15th challenge. The magnitude of the conjunctivitis
      intensity score (CIS), itch-associated scratching response and albumin leakage
      were found to increase with repeated challenges. At the 1st-3rd challenges,
      histamine H(1) receptor antagonist, mepyramine (10 mg/kg, p.o.), strongly reduced
      all these symptoms. However, symptoms at the 5th-15th challenges were not
      inhibited by mepyramine. On the other hand, a nitric oxide synthase (NOS)
      inhibitor, N(omega)-nitro-L-arginine methyl ester (10 mg/kg, i.v.), potently
      inhibited the increase of CIS and albumin leakage at the 15th challenge. In
      conclusion, histamine involvement in the induction of conjunctivitis symptoms in
      our model was diminished by multiple antigen challenges. The allergic
      conjunctivitis at the chronic stage is partly mediated by nitric oxide (NO)
      derived from NOSs that may be activated by mediators other than histamine. The
      histamine-independent allergic conjunctivitis may be useful for analyzing
      mechanisms underlying chronic conjunctivitis.

PMID- 14646174
TI  - Effects of sesamin on aortic oxidative stress and endothelial dysfunction in
      deoxycorticosterone acetate-salt hypertensive rats.
AB  - In the present study, we evaluated the relationship between the antihypertensive
      effect of sesamin, a lignan from sesame oil, and its antioxidative activity in
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 5-week
      treatment period, systolic blood pressure was significantly elevated in normal
      diet-fed DOCA-salt animals compared with cases in sham-operated animals. Sesamin
      feeding, tempol (a superoxide dismutase mimetic) treatment or antihypertensive
      drugs combination (triple therapy; reserpine, hydralazine, hydrochlorothiazide)
      significantly suppressed the development of DOCA-salt-induced hypertension.
      Compared with sham-operated rats, the normal diet-fed DOCA-salt rats revealed
      marked increases in aortic superoxide (O(2)(-)) production. These increases in
      O(2)(-) production were significantly suppressed by sesamin feeding or tempol
      treatment, but not by triple therapy. Acetylcholine (Ach)-induced endothelium
      dependent relaxation was markedly decreased in normal diet-fed DOCA-salt rats,
      compared with cases in sham-operated rats. Sesamin feeding and triple therapy
      significantly improved the DOCA-salt-induced impairment of endothelium-dependent
      relaxation. However, tempol treatment had no effect on the impaired vasodilator
      responses induced by DOCA-salt treatment. In DOCA-salt rats with or without
      sesamin feeding, systolic blood pressure significantly correlated with both
      aortic O(2)(-) production and endothelium-dependent vascular relaxation. These
      findings suggest that sesamin feeding inhibits the enhancement of aortic O(2)(-)
      production in DOCA-salt hypertensive rats, and this effect may contribute to the
      antihypertensive effect of sesamin. Sesamin feeding-induced improvement of
      endothelial dysfunction seems to result from the above antioxidative and
      antihypertensive effects.

PMID- 14646175
TI  - Edaravone, a radical scavenger, may enhance or produce antiproliferative effects
      of fluvastatin, amlodipine, ozagrel, GF109203X and Y27632 on cultured basilar
      artery smooth muscle cells.
AB  - Proliferation of vascular smooth muscle cells stimulated by reactive oxygen
      species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To
      clarify mechanisms by which ROS promote vascular atherogenesis, effects of
      fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a
      protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of
      guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture
      medium were studied over 3 d in the presence or absence of a free radical
      scavenger, edaravone. Viability of cells at the end of incubation was measured by
      the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test.
      Results demonstrated that fluvastatin and amlodipine by themselves possess
      antiproliferative effects on the GBa-SM3 cells at 10-100 microM and 0.1-1 microM,
      respectively. While edaravone possessed no antiproliferative effect by itself at
      100 microM, it significantly (p<0.05) augmented the antiproliferative effects of
      fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed
      no appreciable effects on the cell growth by themselves. However, coincubation of
      edaravone at 100 microM with these agents elicited significant antiproliferative
      effects for ozagrel, GF109203X and Y27632 at 10-100 microM, 1-10 microM and 0.1-1
      microM, respectively. In conclusion, edaravone may have clinically beneficial
      interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of
      vascular atherosclerosis. The interactions between edaravone and the inhibitors
      of protein kinase C and ROCK were suggestive of possible contributions of ROS
      triggered intracellular signals associated with these enzymes to vascular
      atherogenesis, but further studies are required for confirmation.

PMID- 14646176
TI  - Synthesis, analgesic, anti-inflammatory and antibacterial activities of some
      novel 2-methyl-3-substituted quinazolin-4-(3H)-ones.
AB  - A series of novel 2-methyl-3-substituted quinazolin-4-(3H)-ones have been
      synthesized by treating (2-methyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid
      methyl ester with different amines, the starting material dithiocarbamate was
      synthesized from anthranilic acid. The compounds synthesized were investigated
      for analgesic, anti-inflammatory and antibacterial activities. All the test
      compounds exhibited significant activity, the compounds VA2, VA3 and VA4 shown
      more potent analgesic activity, and the compounds VA3 and VA4 shown more potent
      anti-inflammatory activity than the reference compound diclofinac sodium.

PMID- 14646177
TI  - Post-translational modification of betaH-crystallin of bovine lens with aging.
AB  - This study investigates post-translational modification of proteins of bovine
      lens with aging (3 year old vs. 6 month old cows). After water-soluble proteins
      were submitted to gel and ion exchange chromatography, betaH-crystallin, a
      subunit of beta-crystallin, and modified materials were isolated. These materials
      were then submitted to two dimensional polyacrylamide gel electrophoresis (2D-SDS
      PAGE) to detect and isolate the new spots. Results for lens proteins from 3 year
      old animals were compared to those from 6 month old animals. All spots were
      digested in gel with trypsin and the molecular masses of tryptic digests were
      measured by matrix-assisted laser desorption ionization time of flight mass
      spectrometry (MALDI-TOFMS). Peptides peaks obtained from mass mapping were
      identified using the protein database of the MS-Fit program in the Protein
      prospector program of the University of California, San Francisco. We found that
      two post translational modifications of betaH-crystallin, acetylation and
      phosphorylation occurred with aging.

PMID- 14646178
TI  - cis-hinokiresinol, a norlignan from Anemarrhena asphodeloides, inhibits
      angiogenic response in vitro and in vivo.
AB  - cis-Hinokiresinol (CHR) is a norlignan constituent from Anemarrhena asphodeloides
      BUNGE (Liliaceae), which shows hyaluronidase inhibitory activity. In the present
      studies, we have demonstrated that CHR selectively inhibited endothelial cell
      proliferation compared with cancer cells, and especially basic fibroblast growth
      factor (bFGF) or vascular endothelial growth factor (VEGF)-induced endothelial
      cell proliferation. Furthermore, endothelial cell migration and tube formation,
      two important steps in the angiogenic process, were also inhibited by CHR.
      Moreover, CHR reduced the vessel growth induced by VEGF in the mouse corneal
      neovascularization model. These results suggest that CHR may prove useful for the
      development of a novel angiogenesis inhibitor.

PMID- 14646179
TI  - Screening chemical composition and in vitro antioxidant and antimicrobial
      activities of the essential oils from Origanum syriacum L. growing in Turkey.
AB  - In the present study, essential oil from the leaves of Syrian oreganum [Origanum
      syriacum L. (Lauraceae)] grown in Turkish state forests of the Dortyol district,
      Turkey, was obtained by steam distillation. The chemical composition of oil was
      analysed by GC and GC-MS, and was found to contain 49.02% monoterpenes, 36.60%
      oxygenated monoterpenes and 12.59% sesquiterpenes. The major components are as
      follows: gamma-terpinene, carvacrol, p-cymene and beta-caryophyllene.
      Subsequently, the reducing power, antioxidant and 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical-scavenging activities of the essential oil were studied. The
      reducing power was compared with ascorbic acid, and the other activities were
      compared with 2,6-di-tert-butyl-4-methyl phenol (BHT, butylated hydroxytoluene).
      The results showed that the activities were concentration dependent. The
      antioxidant activities of the oil were slightly lower than those of ascorbic acid
      or BHT, so the oil can be considered an effective natural antioxidant.
      Antimicrobial activities of the essential oil from the leaves of Origanum
      syriacum was also determined on 16 microorganisms tested using the agar-disc
      diffusion method, and showed antimicrobial activity against 13 of these.

PMID- 14646181
TI  - Influence of coadministered antiepileptic drugs on serum zonisamide
      concentrations in epileptic patients: quantitative analysis based on suitable
      transforming factor.
AB  - We conducted a study to clarify the most suitable transforming factor related to
      the daily zonisamide dose (D) providing a steady-state serum concentration (C(t))
      and analyzed the influences of the concomitant use of antiepileptic drugs on C(t)
      quantitatively. Data obtained by routine therapeutic drug monitoring from a total
      of 175 epileptic patients treated with the multiple oral administrations of
      zonisamide (ZNS) as a powder/tablets, were used for the analysis. Employing the
      extracellular water volume (V(ECW)) as a transforming factor, led the level/dose
      (L/D) ratio (:C(t)/(D/V(ECW))) to be independent of the patient's age and sex for
      the administration of ZNS alone. C(t) was revealed to be dependent on only one
      variable regarding D/V(ECW) and expressed as C(t)=0.604x(D/V(ECW)). Phenytoin
      (PHT) significantly lowered (p<0.01) the L/D ratio to 0.76 of the value for ZNS
      alone. For a more detailed analysis, we defined the parameter R(i) (i=1, 2, em
      leader, 6) as an alteration ratio, representing the influence of each
      antiepileptic drug on the L/D ratio of ZNS alone. A model based on the assumption
      that each R(i) value was independent from one another and multiplicative, was
      adopted. The analysis clarified that phenobarbital, valproic acid, carbamazepine,
      and PHT significantly lowered (p<0.05) the L/D ratio of ZNS to 0.849, 0.865,
      0.846, and 0.804, respectively. In the case of the addition or discontinuance of
      concomitant treatment with antiepileptic drugs in the same patient, the estimated
      L/D ratios were calculated using the value of each R(i) and compared with the
      measured ones. The mean of prediction error was calculated as 22.9%. Our results
      appear valid and R(i) should be available for clinical use.

PMID- 14646180
TI  - Trypanocidal constituents in plants 2.xanthones from the stem bark of Garcinia
      subelliptica.
AB  - The constituents of the stem bark of Garcinia subelliptica (Guttiferae) were
      investigated based on its trypanocidal activity against epimastigotes of
      Trypanosoma cruzi, the etiologic agent for Chagas' disease. As the active
      components, nine xanthones were isolated including two new ones, 4
      hydroxybrasilixanthone B and 1,3,5,6-tetrahydroxy-4,7,8-tri(3-methyl-2
      butenyl)xanthone. Their structures were determined by spectroscopic analysis.
      Trypanocidal activity against trypomastigotes, an infectious form of T. cruzi,
      was also estimated as well as cytotoxic activity. Fukugetin, the major component
      of the bark, showed no activity.

PMID- 14646182
TI  - Effect of mixed micelle formulations including terpenes on the transdermal
      delivery of diclofenac.
AB  - The significant inhibitory action of diclofenac formulated in mixed micelles of
      lecithin with cholate or deoxycholate was observed on the rat hind paw edema
      induced by carrageenan. In the primary stage, mixed micelle formulation of
      deoxycholate was more effective compared with that of cholate. However, in the
      final term, the inhibitory action was similar in both formulations. In a previous
      study, the flux of diclofenac was greater in the mixed micelle formulation of
      deoxycholate compared with that of cholate. It was suggested that the permeation
      rate of diclofenac through skin was proportional to the pharmacological activity.
      The hind paw edema was quickly inhibited when cyclic monoterpene such as d
      limonene or l-menthol was included in the formulations. All the micelle
      formulations significantly decreased the value of AUC estimated the hind paw
      thickness-time profile. This suggests that the micelle formulation of cholate in
      addition to deoxycholate showed significant anti-inflammatory activity to hind
      paw edema of rats. Incorporation of d-limonene or l-menthol was more effective on
      the decrease of AUC. A pharmacological study revealed that micelle formulations
      were able to reduce the skin irritation of chemicals.

PMID- 14646183
TI  - Bioavailability of theophylline and thiamine disulfide incorporated into
      mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate
      butyrate.
AB  - Mucoadhesive microspheres made of oppositely charged dextran derivatives and
      cellulose acetate butyrate (Ad-MS) were evaluated for their ability to improve
      the bioavailability of theophylline (TH) and thiamine disulfide (TDS). A drug
      suspension (or solution) and non-adhesive microspheres (MS) were used as
      references. In vitro drug release profiles from MS and Ad-MS were similar for
      each drug, whereas their gastrointestinal transits differed. The plasma
      concentration after oral administration of drug suspension (or solution), MS and
      Ad-MS was investigated in rats. In the case of TH, sustained plasma level
      profiles were observed after MS or Ad-MS administration, with similar C(max),
      T(max) and MRT( infinity ) values. AUC( infinity ) values of the suspension, MS
      and Ad-MS were statistically equivalence. These indicated that Ad-MS achieved a
      sustained plasma level profile without a decrease of AUC. In the case of TDS,
      MRT( infinity ) and AUC( infinity ) of Ad-MS were significantly larger than those
      of the solution and MS, indicating that the plasma level was sustained and the
      extent of bioavailability was increased. These results suggested that Ad-MS is a
      promising device for improvement of bioavailability of drugs those absorption
      windows are limited to upper part of the gastrointestinal tract.

PMID- 14646185
TI  - Screening of the inhibitory effect of vegetable constituents on the aryl
      hydrocarbon receptor-mediated activity induced by 2,3,7,8-tetrachlorodibenzo-p
      dioxin.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription
      factor that mediates responses to environmental contaminants such as dioxins,
      which have many adverse health effects. We performed a preliminary screening of
      the inhibitory effects of vegetable constituents on 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD)-induced activation of AhR using the AhR-based bioassay for dioxins,
      the Ah-Immunoassay. Ninety vegetable constituents including flavonoids, tannins,
      saponins, terpenes, etc., were assayed in vitro. Among them, flavones, flavonols,
      anthraquinones, piperine, coumestrol, brevifolincarboxylic acid, and resveratrol
      showed marked inhibitory effects on AhR-based bioassay activation by TCDD, and
      their effects were dose dependent. Curcumin, carnosol, and capsaicin also
      inhibited the activation of AhR in this assay, although to a lesser degree. These
      results suggest that several vegetable constituents might play a role in
      protection against dioxin toxicity.

PMID- 14646184
TI  - Effects of Bak Foong Pills and Menoease Pills on white blood cell distribution in
      old age female rats.
AB  - This study examined the effects of Bak Foong Pills (BFP) and the new BFP-derived
      post-menopause formula, Menoease Pills (MBFP), on the distribution of peripheral
      white blood cells (WBC) between BFP/MBFP-treated and non-treated rats. Eighteen
      months old female SD rats were used to mimic post-menopausal and old age animal
      models. The percentage distribution of lymphocytes, monocytes and granulocytes
      were measured using flow cytometry with and without treatments of BFP or MBFP.
      Results showed that WBC distribution in old age rats were significantly different
      from that of adult rats, suggesting that as the animal aged, their WBC
      distributions were altered. Old age rats were observed to have much lower
      percentages of lymphocytes, but higher percentages of granulocytes when compared
      to the adult rats, indicating possible attenuated immunity. Following treatment
      with BFP or MBFP, WBC populations were found to be redistributed back into the
      ranges observed in adult animals. Furthermore, MBFP, was found to alter WBC
      distribution in a dose-dependent manner. When compared to estrogen (E(2)), a well
      documented regulator of immune function, results showed that MBFP was able to
      show significantly greater effects on WBC redistribution compared to E(2).
      However, in ovariectomised (ovx) old age rats, neither MBFP nor E(2) treated
      groups showed any changes in WBC redistribution. These results indicate that MBFP
      may share similarities to E(2). Indeed, the effect of MBFP and E(2) seems to
      require intact ovaries, which are believed to be necessary for the modulation of
      WBC distributions and immune functions. Overall, our findings suggest that BFP
      and MBFP may be able to regulate WBC population in old age female rats, and thus,
      indicate their potential role on improving the attenuated immunity evident in
      post-menopausal and elderly women.

PMID- 14646186
TI  - Further studies on the kidney- and site-selective delivery of 5-fluorouracil
      following kidney surface application in rats.
AB  - The present study was undertaken to elucidate the kidney- and site-selective
      delivery of 5-fluorouracil (5-FU) following kidney surface application in rats.
      We selected an experimental system utilizing a cylindrical diffusion cell
      attached to the right kidney surface. After 5-FU was applied to this surface,
      approximately 60% was absorbed in 180 min. A semi-log plot of the remaining
      amount of 5-FU in the diffusion cell gave a straight line. The cumulative amount
      of urinary excretion of 5-FU for up to 180 min from the right ureter was
      significantly higher than that from the left ureter. On the other hand, the
      cumulative amount of urinary excretion of 5-FU from the right and left ureters
      after intravenous administration of the drug was similar. The 5-FU concentration
      at four sites in the right kidney after intravenous administration was also
      similar, while the drug was site-selectively delivered in the kidney after its
      surface application. 5-FU accumulated at the site under the diffusion cell was
      rapidly eliminated after its removal from the diffusion cell. From these results,
      we demonstrated that the absorption of 5-FU on the kidney surface in rats is
      explained mostly by passive diffusion. It was further elucidated that kidney
      surface application of this drug in rats results in its the kidney- and site
      selective delivery.

PMID- 14646187
TI  - Calpain 10 as a predictive gene for type 2 diabetes: evidence from a novel
      screening system using white blood cells of Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats.
AB  - The mRNA expression of type 2 diabetes-related genes in white blood cells (WBC)
      was examined before and after onset in Otsuka Long-Evans Tokushima Fatty (OLETF)
      rat. The level of the calpain 10 (CAPN10) transcript was significantly decreased
      compared to control animals in WBC before and after onset. Significant decreases
      in this gene expression were also found in the major insulin-target tissues as
      well as WBC before onset. These results suggest that gene expression in WBC could
      be a useful screening system for predicting the incidence of type 2 diabetes
      before onset in OLETF rats, and that CAPN10 represents a potential candidate gene
      for predicting type 2 diabetes in human.

PMID- 14646188
TI  - DPPH radical scavengers from dried leaves of oregano (Origanum vulgare).
AB  - 1,1-Dipehnyl-2-picrylhydrazyl (DPPH) radical scavenging activities were found in
      the extract of dried leaves of oregano (Origanum vulgare). The water-soluble
      active ingredients were isolated, and their structures were determined to be 4'-O
      beta-D-glucopyranosyl-3',4'-dihydroxybenzyl protocatechuate and 4'-O-beta-D
      glucopyranosyl-3',4'-dihydroxybenzyl 4-O-methylprotocatechuate by (1)H-, (13)C
      NMR, DEPT, HMQC, and HMBC spectral analyses, and by NOE experiments. The DPPH
      radical scavenging activities of these compounds were compared with those of
      rutin, quercetin and rosmarinic acid at a concentration of 2 x 10(-5) M. The
      scavenging activity of 4'-O-beta-D-glucopyranosyl-3',4'-dihydroxybenzyl
      protocatechuate was almost the same as that of quercetin and rosmarinic acid, but
      that of 4'-O-beta-D-glucopyranosyl-3',4'-dihydroxybennzyl 4-O
      methylprotocatechuate was less than that of quercetin, rosmarinic acid and 4'-O
      beta-D-glucopyranosyl-3',4'-dihydroxybenzyl protocatechuate. The amount of 4'-O
      beta-D-glucopyranosyl-3',4'-dihydroxybenzyl protocatechuate was estimated to be
      3.8 mg/1 g of dried leaves by an HPLC analysis.

PMID- 14646189
TI  - Transepithelial transport of p-coumaric acid and gallic acid in Caco-2 cell
      monolayers.
AB  - The transepithelial transport of such common dietary phenolic acids as p-coumaric
      acid (CA) and gallic acid (GA) across Caco-2 cell monolayers was examined. CA
      transport was dependent on pH, and in a vectorial manner in the apical
      basolateral direction. The permeation was concentration-dependent and saturable,
      the Michaelis constant and maximum velocity being 17.5 mM and 82.7 nmol min(-1)
      (mg of protein)(-1), respectively. Benzoic acid and acetic acid inhibited the
      permeation of CA. These results indicate that the transepithelial transport of CA
      was via the monocarboxylic acid transporter (MCT). On the other hand, the
      permeation of GA was not in a polarized manner, was independent of pH and
      linearly increased with increasing concentration of GA. The transport rate of GA
      was about 100 times lower than that of CA, suggesting the transepithelial
      transport of GA to be via the paracellular pathway. Dietary phenolic acids thus
      showed diversified characteristics in their intestinal absorption.

PMID- 14646190
TI  - Effects of intake of a mixture of thiamin, arginine, caffeine, and citric acid on
      adiposity in healthy subjects with high percent body fat.
AB  - We assessed the effects of intake of thiamin, arginine, caffeine, and citric acid
      (TACC) on lipid metabolism in healthy subjects. Thirty-one subjects with high
      percent body fat (> or = 25.0%) were randomly assigned to a 12-wk intervention
      with daily intake of TACC-supplemented tea (1.1, 1240, 52, and 540 mg,
      respectively; n=16) or control tea (n=15). The percent body fat decreased
      significantly during the intervention in both groups, especially in the TACC
      group. A percentage decrease in triceps skinfold was significantly greater in the
      TACC group than in the control group. The decrease in abdominal visceral fat in
      obese subjects was significantly greater in the TACC group than in the control
      group. Serum triglyceride was significantly lower during intervention than that
      during the non-intervention period in the TACC group. These results suggest that
      TACC may be effective in reducing body fat in obese subjects.

PMID- 14646191
TI  - Functional properties of glycosylated lysozyme secreted in Pichia pastoris.
AB  - Various mutant lysozymes having the N-glycosylation signal sequence, R21T
      (Asn(19)-Tyr(20)-Thr(21)), G49N (Asn(49)- Ser(50)-Thr(51)), R21T/G49N (Asn(19)
      Tyr(20)-Thr(21)/Asn(49)-Ser(50)-Thr(51)), were secreted in the Pichia pastoris
      expression system. The secreted amounts of these mutant glycosylated lysozymes
      were almost the same as those of wild-type lysozyme (about 30 mg/liter).
      Glycosylation of the mutant lysozymes was confirmed by SDS-PAGE patterns, Endo-H
      treatment, TOF-MS analysis and chemical analysis. The composition of the
      carbohydrate chain attached to the single glycosylated lysozymes, R21T and G49N,
      was GlcNAc(2)Man(9-11), while that of the double glycosylated lysozyme,
      R21T/G49N, was GlcNAc(4)Man(27-32). The results of a CD analysis and lytic
      activity suggested that the conformation of the single glycosylated lysozymes had
      been conserved, while that of the double glycosylated lysozyme was less stable.
      The emulsifying properties of the lysozyme when glycosylated were greatly
      improved, being especially noteworthy in the double glycosylated lysozyme.

PMID- 14646192
TI  - Adenovirus-mediated suicide gene therapy using the human telomerase catalytic
      subunit (hTERT) gene promoter induced apoptosis of ovarian cancer cell line.
AB  - Telomerase is a ribonucleoprotein complex the function of which is to add
      telomeric repeats (TTAGGG)(n) to chromosomal ends, and it is known to play an
      important role in cellular immortalization. Telomerase is highly active in most
      tumor cells, yet not in normal cells. As such, it may have possible applications
      in cancer gene therapy. Telomerase consists of two essential components,
      telomerase RNA template (hTR) and catalytic subunit (hTERT). hTERT is expressed
      only in cells and tissues positive for telomerase activity, i.e., tumor and fetal
      cells. We here tested the possibility of the utilization of the hTERT promoter in
      targeted cancer gene therapy. We cloned the hTERT promoter in the replace of the
      CMV promoter and sub-cloned HSV-TK gene to be controlled by hTERT gene promoter
      in adenovirus shuttle plasmid. Then we constructed recombinant adenovirus Ad-hT
      TK, and infected them into normal and human gynecological cancer cell lines.
      Through these experiments, we identified the selective tumor specific cell death
      by Ad-hT-TK. Furthermore, FACS analysis and TUNEL assay suggests that the reduced
      viability is mediated through the induction of apoptosis, indicating that this
      approach may be a useful method for suppressing cancer growth in targeted cancer
      gene therapy. These results show that Ad-hT-TK could be used for gynecological
      cancer gene therapy.

PMID- 14646193
TI  - Cloning and functional analysis of aniline dioxygenase gene cluster, from
      Frateuria species ANA-18, that metabolizes aniline via an ortho-cleavage pathway
      of catechol.
AB  - Genes encoding an aniline dioxygenase of Frateuria sp. ANA-18, which metabolizes
      aniline via the ortho-cleavage pathway of catechol, were cloned and named tdn
      genes. The tdn genes were located on the chromosomal DNA of this bacterium and
      weren't clustered with catechol-degrading gene clusters. These results show that
      the ANA-18 aniline-degrading gene cluster is constructionally different from
      Pseudomonas tdn and Acinetobacter atd gene clusters, which degrade aniline via
      the meta-cleavage pathway of catechol and organize catechol-metabolic genes in
      the gene clusters. When cloned tdnQTA1A2B genes were expressed in Eschherichia
      coli, aniline dioxygenase activity was observed. Southern blot analysis revealed
      that homologues of the tdnA1A2B genes didn't exist in strain ANA-18. Disruption
      of the tdnA1A2 genes gave the parent strain ANA-18 a defect in aniline
      metabolism. On the basis of these results, we concluded that only the cloned tdn
      genes function as genes encoding aniline dioxygenase in strain ANA-18 although
      this bacterium had two catechol-degrading gene clusters.

PMID- 14646194
TI  - A thermostable non-xylanolytic alpha-glucuronidase of Thermotoga maritima MSB8.
AB  - A putative alpha-glucosidase belonging to glycosyl hydrolase family 4 of
      Thermotoga maritima (TM0752) was expressed in Escherichia coli and it was found
      that the recombinant protein (Agu4B) was a p-nitrophenyl alpha-D
      glucuronopyranoside hydrolyzing alpha-glucuronidase, not alpha-glucosidase. It
      did not hydrolyze 4-O-methyl-D-glucuronoxylan or its fragment oligosaccharides.
      Agu4B was thermostable with an optimum temperature of 80 degrees C. It strictly
      required Mn(2+) and thiol compounds for its activity. The presence of NAD(+)
      slightly activated the enzyme. The amino acid sequence of Agu4B showed higher
      identity with Agu4A (another alpha-glucuronidase of T. maritima, 61%) than with
      AglA (alpha-glucosidase of T. maritima, 48%).

PMID- 14646195
TI  - Inhibition of chromosome separation in fertilized starfish eggs by kalihinol F, a
      topoisomerase I inhibitor obtained from a marine sponge.
AB  - Kalihinol F, a naturally occurring diterpene from a marine sponge, Acanthella
      sp., inhibited chromosome separation in fertilized starfish (Asterina
      pectinifera) eggs but allows the first cleavage to occur, thereby forming
      unseparated metaphase chromosomes which were elongated between the two daughter
      cells. The chromosomes were eventually torn off in the embryonic cells. Most of
      the cells gradually lost the chromosomes during the cell cycle progression. The
      embryonic development halted at the morula stage just before the onset of
      blastulation. The mitotic failure occurred when kalihinol F was applied to a
      fertilized egg during the second meiotic process, but not after the completion of
      the second meiotic division. Kalihinol F inhibited topoisomerase I activity in
      vitro, but had no effects on activities of DNA polymerases alpha, beta, and
      gamma, and of topoisomerase II. These results suggest that the topoisomerase I
      plays an essential role in meiosis II in this species.

PMID- 14646196
TI  - Gene cloning and function analysis of replication factor C from Thermococcus
      kodakaraensis KOD1.
AB  - Replication factor C (RFC) catalyzes the assembly of circular proliferating cell
      nuclear antigen (PCNA) clamps around primed DNA, enabling processive synthesis by
      DNA polymerase. The RFC-like genes, arranged in tandem in the Thermococcus
      kodakaraensis KOD1 genome, were cloned individually and co-expressed in
      Escherichia coli cells. T. kodakaraensis KOD1 RFC homologue (Tk-RFC) consists of
      the small subunit (Tk-RFCS: MW=37.2 kDa) and the large subunit (Tk-RFCL: MW=57.2
      kDa). The DNA elongation rate of the family B DNA polymerase from T.
      kodakaraensis KOD1 (KOD DNA polymerase), which has the highest elongation rate in
      all thermostable DNA polymerases, was increased about 1.7 times, when T.
      kodakaraensis KOD1 PCNA (Tk-PCNA) and the Tk-RFC at the equal molar ratio of KOD
      DNA polymerase were reacted with primed DNA.

PMID- 14646197
TI  - Cholesterol esterase bound to intestinal brush border membranes does not
      accelerate incorporation of micellar cholesterol into absorptive cells.
AB  - We confirmed that cholesterol esterase accelerated the incorporation of
      unesterified cholesterol solubilized in bile salt micelles into differentiated
      Caco-2 cells under various experimental conditions. Rat pancreatic juice and
      bovine cholesterol esterase increased the incorporation of micellar cholesterol
      into rat intestinal brush border membranes. The incorporation of micellar
      cholesterol was not changed in the brush border membranes enriched in and
      depleted of cholesterol esterase. The results suggest that the accelerated
      incorporation of micellar cholesterol by cholesterol esterase into absorptive
      cells is not mediated by the enzyme bound to the brush border membranes.

PMID- 14646198
TI  - Improvement of GFPuv-beta 3GnT2 fusion protein production by suppressing protease
      in baculovirus expression system.
AB  - The effects of protease inhibitors on the production of recombinant protein were
      investigated using a recombinant baculovirus containing GFPuv-human beta 1,3-N
      acetylglucosaminyltransferase 2 (beta 3GnT2) connected to the prepromelittin
      signal sequence. The addition of leupeptin as a cysteine protease inhibitor at
      2.5 microg/ml improved intra- and extracellular beta 3GnT activities 5- and 3
      fold, respectively, compared to those without addition, which was due to a
      suppression of protease activity. With the leupeptin addition only four degraded
      molecular bands lower than 32 kDa appeared, but 9 degraded molecular bands
      between 29 kDa and 41 kDa existed without addition. In contrast, pepstatin A as a
      carboxyl protease inhibitor had no influence on the improvement of beta 3GnT
      production, judging from SDS-PAGE. Moreover, when 50 microM carbobenzoxy-L-leucyl
      L-leucyl-L-leucinal (MG-132), known as a proteasome inhibitor, was used in
      combination with the leupeptin, a ladder of low molecular mass bands of fusion
      protein was diminished. The intracellular beta 3GnT activity increased 9-fold, to
      as high as that without addition of two kinds of protease, but the extracellular
      activity was not different from that with the addition of only leupeptin. These
      findings indicate that the decrease in cell viability causes the decrease in the
      secretion rate of intracellular fusion protein, resulting the accumulation of the
      full-length of fusion protein.

PMID- 14646199
TI  - Characterization of streptozotocin-induced diabetic rats and pharmacodynamics of
      insulin formulations.
AB  - Morphological and functional changes of rat pancreatic islets caused by
      administration of streptozotocin (STZ) and the bioavailability of insulin
      formulations administered to STZ-induced diabetic rats with fasting (12 h) or non
      fasting were investigated. Islets isolated from normal rats maintained a good
      three-dimensional structure and the islet yield was 962.5+/-86.5 islet equivalent
      number (IEQ, islets converted to an average diameter of 150 microm). In the
      diabetic group (>500 mg/ml blood glucose), the islet yield was only 44.4+/-8.3
      IEQ and the islet was severely damaged. The minimum reduction of blood glucose of
      each formulation, such as insulin solution, microcrystal, and insulin
      microcrystal capsule, was shown to be 11.3, 11.0, and 16.3 mg/dl, respectively,
      at 6 h in fasting with diabetic rats. These results indicated that the
      administration of insulin formulations to the fasting groups increased the severe
      hypoglycemic effect of insulin action more than in non-fasting diabetic rats. The
      diabetic rat with fasting has a regulatory disorder in maintaining the blood
      glucose level. Accordingly, the validity of pharmacological availability as an
      optimal modeling of insulin formulations is best in non-fasting STZ-induced
      diabetic rats.

PMID- 14646200
TI  - Carbohydrate binding specificity of the recombinant chitin-binding domain of
      human macrophage chitinase.
AB  - The chitin-binding domain of human macrophage chitinase was expressed as a fusion
      protein with glutathione S-transferase in Escherichia coli and assayed for its
      binding activity. The purified recombinant chitin-binding domain bound to chitin,
      but not to glucan, xylan, or mannan. The binding of the recombinant chitin
      binding domain to chitin was inhibited by N-acetylglucosamine, di-N
      acetylchitobiose, and hyaluronan, but not by N-acetylgalactosamine or
      chondroitin. Furthermore, a solid-phase binding assay showed that the recombinant
      domain interacts specifically with hyaluronan and hybrid-type N-linked
      oligosaccharide chains on glycoproteins, and that the oligosaccharide-binding
      characteristics are similar to those of wheat germ agglutinin, a lectin that
      binds to chitin. The results suggest that human chitinase chitin-binding domain
      may be involved in tissue remodeling through binding to polysaccharides or
      extracellular matrix glycoproteins, and this recombinant protein can be used to
      elucidate biological functions of the enzyme.

PMID- 14646201
TI  - Deuterium-labeled phaseic acid and dihydrophaseic acids for internal standards.
AB  - The concentration of abscisic acid in plants is regulated not only by
      biosynthesis, but also by metabolism. Abscisic acid is metabolized to phaseic
      acid via 8'-hydroxyabscisic acid, and phaseic acid is then converted to
      dihydrophaseic acid and its epimer. A quantitative analysis of these metabolites
      is important as well as that of abscisic acid to understand changes in the
      concentration of abscisic acid in plants. However, no internal standards of the
      metabolites suitable for quantitative analysis have been reported. We prepared 7'
      deuterium-labeled phaseic acid with a deuterium content of 86%, using the
      equilibrium reaction between phaseic acid and 8'-hydroxyabscisic acid. 7'
      Deuterium-labeled dihydrophaseic acids were obtained by reducing 7'-deuterium
      labeled phaseic acid. The levels of the metabolites in plant organs were
      determined by using the deuterated metabolites as internal standards.

PMID- 14646202
TI  - A Corynebacterium glutamicum rnhA recG double mutant showing lysozyme
      sensitivity, temperature-sensitive growth, and UV-sensitivity.
AB  - Corynebacterium glutamicum mutant KY9707 was originally isolated for lysozyme
      sensitivity, and showed temperature-sensitive growth. Two DNA fragments from a
      wild-type C. glutamicum chromosomal library suppressed the temperature
      sensitivity of KY9707. These clones also rescued the lysozyme-sensitivity of
      KY9707, although partially. One of them encodes a protein of 382 amino acid
      residues, the N-terminal domain of which was homologous to RNase HI. This gene
      suppressed the temperature-sensitive growth of an Escherichia coli rnhA rnhB
      double mutant. We concluded that this gene encodes a functional RNase HI of C.
      glutamicum and designated it as rnhA. The other gene encodes a protein of 707
      amino acid residues highly homologous to RecG protein. The C. glutamicum recG
      gene complemented the UV-sensitivity of E. coli recG258::kan mutant. KY9707
      showed increased UV-sensitivity, which was partially rescued by either the recG
      or rnhA gene of C. gluamicum. Point mutations were found in both recG and rnhA
      genes in KY9707. These suggest that temperature-sensitive growth, UV-sensitivity,
      and probably lysozyme-sensitivity also, of KY9707 were caused by mutations in the
      genes encoding RNase HI and RecG.

PMID- 14646203
TI  - Reduction of antigenicity of Cry j I, major allergen of Japanese cedar pollen, by
      the attachment of polysaccharides.
AB  - An attempt was made to mask the allergenic structure of a major allergen protein,
      Cry j I (CJI), in Japanese cedar pollen using the Maillard-type polysaccharide
      conjugation. The SDS-PAGE pattern of the CJI-galactomannan conjugate prepared by
      the Maillard reaction showed broad bands widely distributed from 50 kDa to more
      than 100 kDa, suggesting the attachment of galactomannan. The competitive enzyme
      linked immunosorbent assay showed that the IgE antibody in the sera of cedar
      pollen-sensitive patients reacted strongly with CJI, while it did not react with
      the CJI-galactomannan conjugate. This result suggests that the antigenicity of
      CJI is greatly reduced by the conjugation with galactomannan.

PMID- 14646204
TI  - A stearoyl-CoA-specific Delta 9 fatty acid desaturase from the basidiomycete
      Lentinula edodes.
AB  - A gene encoding a Delta 9 fatty acid desaturase (Delta 9-desaturase) was isolated
      from L. edodes. The open reading frame of this gene (named Le-FAD1) consisted of
      1416 bp. The predicted protein of 471 amino acids shares 47-57% sequence identity
      with Delta 9-desaturases from other fungi. Expression of the Le-FAD1 ORF
      complemented genetic disruption of the Saccharomyces cerevisiae OLE1 gene (Sc
      OLE1). Fatty acid analysis of the Le-FAD1-expressing S. cerevisiae ole1-disrupted
      strain showed that Le-FAD1 protein had slight activity with palmitic acid (16:0)
      as the substrate and high activity with stearic acid (18:0). Analysis of
      transcriptional expression showed that the levels of Le-FAD1 mRNA in the
      primordium and fruiting body of L. edodes were higher than in mycelia cultivated
      at 18 degrees C as well as 25 degrees C. These results correlated with the
      increase of unsaturated fatty acids (UFAs) in total lipids during fruiting-body
      formation.

PMID- 14646206
TI  - Effects of gamma-terpinene on lipid concentrations in serum using Triton WR1339
      treated rats.
AB  - We studied lipid metabolism to evaluate the effects of gamma-terpinene on
      suppression of increases in serum lipid concentrations using Triton WR1339
      treated rats. At 6 hr after Triton WR1339 injection, the total cholesterol and
      triglyceride concentrations in the gamma-terpinene group underwent statistically
      significant decreases (18.3 and 30.3%, respectively) compared with those of the
      Triton-treated group.

PMID- 14646205
TI  - Gibberellin is essentially required for carrot (Daucus carota L.) somatic
      embryogenesis: dynamic regulation of gibberellin 3-oxidase gene expressions.
AB  - A GA biosynthesis inhibitor, uniconazole, caused many shrunken embryos when it
      was supplied to cultured carrot (Daucus carota L.) cells at the induction of
      somatic embryos. The abnormality was prevented by exogenous GA(1) or GA(4). To
      analyze the status of GA biosynthesis during somatic embryogenesis, expression
      patterns of newly isolated genes encoding GA biosynthetic enzymes, two GA 20
      oxidases, three GA 3-oxidases, and two GA 2-oxidases were observed by using a
      semi-quantitative reverse-transcription-polymerase chain reaction with gene
      specific primers. Transcript levels of GA 20-oxidases and GA 2-oxidases did not
      change greatly during development of the somatic embryo. On the other hand,
      drastic changes were found in three GA 3-oxidase genes. Strikingly, expression of
      a GA 3-oxidase gene, DcGA3ox2, was elevated once in somatic embryogenesis, but
      not in the non-induced suspension cells. The enzymatic functions of these gene
      products were also confirmed using recombinant proteins expressed in Escherichia
      coli. Our results indicate that GA biosynthesis is required for carrot somatic
      embryogenesis.

PMID- 14646207
TI  - Triiodothyronine but not thyroxine accelerates myofibrillar proteolysis via ATP
      production in cultured muscle cells.
AB  - These experiments were done to clarify that the differential effects of thyroxine
      (T(4)) and triiodothyronine (T(3)) on skeletal muscle protein turnover are caused
      by their roles on ATP production. Primary cultured chick muscle cells were
      treated with a physiological level of T(4) (60 ng/ml), T(3) (12 ng/ml), or ATP
      (0.5 mM) for 6 days and the protein content, ATP production, proteasome activity,
      and myofibrillar protein breakdown were measured. The protein content measured as
      an index of cell growth was not affected by T(4), T(3), or ATP. The cellular ATP
      level was increased by T(3) and ATP, but not by T(4). Proteasome activity and
      N(tau)-methylhistidine (MeHis) release measured as an index of myofiblillar
      protein breakdown was also increased by T(3) and ATP, but not by T(4). These
      results indicate that T(3) but not T(4) increases ATP production followed by an
      increase in proteasome activity, and thus stimulates myofibrillar proteolysis.

PMID- 14646208
TI  - Effects of serum deprivation on myofibrillar proteolysis in chick myotube
      cultures.
AB  - We examined the effects of serum deprivation on myofibrillar proteolysis in chick
      myotubes. Myotubes were incubated with serum-free medium for 24 hours. N(tau)
      methylhistidine release, as an index of myofibrillar proteolysis, as well as
      protease activities such as calpain, proteasome, and cathepsins (B+L and D)
      activities were increased by serum deprivation. These results indicate that serum
      deprivation induces calpain, proteasome, and cathepsins activities, resulting in
      an increase in myofibrillar proteolysis in chick myotubes.

PMID- 14646209
TI  - Viable cell detection by the combined use of fluorescent glucose and fluorescent
      glycine.
AB  - The combined use of a fluorescent glucose (2NBDG) and a fluorescent glycine (NBD
      Gly) was tried for the detection of viable cells of significant foodborne
      pathogenic strains in addition to several Escherichia coli strains and coliforms.
      Thirty-five out of 41 strains showed marked uptake of 2NBDG but 6 strains were
      not able to take in 2NBDG. Five out of these 6 strains showed NBD-Gly uptake.

PMID- 14646210
TI  - Synthesis and antioxidant activity of 4-[2-(3,5-dimethoxyphenyl)ethenyl]-1,2
      benzenediol, a metabolite of Sphaerophysa salsula.
AB  - 4-[2-(3,5-Dimethoxyphenyl)ethenyl]-1,2-benzenediol (7), a stilbene isolated from
      Sphaerophysa salsula, was synthesized from 3,4-dihydroxybenzaldehyde (1) in five
      steps in an overall yield of 33%. The spectral data for synthetic 7 are in good
      agreement with those of the natural product. Hydroxystilbene 7 showed potent
      antioxidative activity.

PMID- 14646211
TI  - Effects of oxygenated carotenoid beta-cryptoxanthin on morphological
      differentiation and apoptosis in Neuro2a neuroblastoma cells.
AB  - Beta-Cryptoxanthin (beta Cx) was investigated for cell functions in neuroblastoma
      Neuro2a cells. The following results were obtained. 1. Beta-Cx induced neurite
      outgrowth. 2. Beta-Cx inhibited the etoposide-induced activation of caspase-3
      activity in a dose-dependent manner. These data suggest a bioregulatry function
      of beta Cx in the control of differentiation and apoptosis in Neuro2a cells.

PMID- 14646212
TI  - Damage to cultivated Japanese pearl oysters by oxidative stress that was related
      to "mass mortality".
AB  - Increased blood-DNA breakage was observed in diseased pearl oysters. They showed
      significant formation of 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde
      (MDA), whereas the oysters that had a low mortality rate from the disease had
      high activity of superoxide dismutase (SOD) and low amounts of 8-OHdG and MDA.
      These results suggest that radical damage had occurred only in the diseased pearl
      oysters with the cytolysis of their haemocytes, which was related to the mass
      mortality of the Japanese pearl oysters.

PMID- 14646213
TI  - Improvement of reverse transcription PCR by RNase H.
AB  - An improvement in the method of the Reverse Transcription PCR (RT-PCR) using
      RNase H is proposed here. We succeeded in RT-PCR amplification against the full
      sequence of the coding region (8.9 kb) of the Insulin-like growth factor II
      receptor gene which has the area called the GC-block of about 90% GC contents at
      the 5' terminal. Furthermore, the RNase H treatment improved the sensitivity of
      RT-PCR amplification against a general target.

PMID- 14646214
TI  - Inhibition of sortase, a bacterial surface protein anchoring transpeptidase, by
      beta-sitosterol-3-O-glucopyranoside from Fritillaria verticillata.
AB  - A glucosylsterol, beta-sitosterol-3-O-glucopyranoside, has been isolated as an
      active principle with sortase inhibitory effect from the bulbs of Fritillaria
      verticillata by bioassay-guided chromatographic fractionation. The isolate was a
      potent inhibitor of sortase, with an IC(50) value of 18.3 microg/ml and had
      antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and
      Micrococcus leuteus with MIC values of 50, 200, and 400 microg/ml, respectively,
      indicating that this compound is a possible candidate for the development of a
      bacterial sortase inhibitor. In addition, sitosterol was found to be inactive
      upon sortase and bacterial cell growth. These results suggest that the inhibitory
      potency of beta-sitosterol-3-O-glucopyranoside is sensitively dependent upon the
      glucopyranoside side chain moiety.

PMID- 14646215
TI  - Occurrence of coenzyme forms of vitamin B12 in a cultured purple laver (Porphyla
      yezoensis).
AB  - Porphyra yezoensis (Susabinori, an edible purple laver), which was cultured
      aseptically for 12 weeks and then lyophilized, contained 50+/-2 microg/g of
      vitamin B(12) per 100 g dry weight. Coenzyme forms of vitamin B(12) (about 60% of
      the total vitamin B(12)) were found in the cultured purple laver aseptically,
      which may have the ability to biosynthesize the coenzymes.

PMID- 14646216
TI  - Effect of enzymatic modification of dietary wheat flour for reducing its
      allergenicity on oral sensitization to and intestinal absorption of ovalbumin.
AB  - Increase in plasma immunoglobulin G specific to orally administered ovalbumin in
      Brown Norway rats was retarded by feeding enzyme-treated wheat flour when
      compared with untreated flour. Because plasma ovalbumin concentrations after
      feeding ovalbumin tended to be lower in mice fed enzyme-treated flour than in
      those fed untreated flour, suppression of ovalbumin absorption may be relevant to
      retarded sensitization observed in rats.

PMID- 14646217
TI  - Proteome analysis of wheat lemma.
AB  - We report here for the first time on the construction of proteomes from wheat
      lemma at the anthesis stage. After transfer of lemma proteins to polyvinylidene
      difluoride membranes, seventy larger spots were subjected to peptide sequence
      analysis; the amino acid sequences could be described for forty-eight of these
      proteins. The result suggested that wheat proteins were less N-terminally blocked
      compared to rice proteins, which are known to have a much higher ratio of N
      terminal blocks. We further analyzed the internal sequences of eight blocked
      proteins by the Cleveland peptide mapping method. Out of these total 56 amino
      acid sequences, forty-one could be assigned to the corresponding expressed
      sequence tags (ESTs). The expression profile of lemma proteins was generally
      similar to that of leaf, and the majority of identified proteins were related to
      cellular metabolisms. We analyzed the internal sequences of one protein spot
      present in lemma, which was not present in leaf.

PMID- 14646218
TI  - Immunological detection of proteolytically activated epidermal-type
      transglutaminase (TGase 3) using cleavage-site-specific antibody.
AB  - Transglutaminase 3 (TGase 3), involved in the cross-linking of structural
      proteins in the epidermis, is activated by limited proteolysis of zymogen into
      two fragments during keratinocyte differentiation. Using recombinant TGase 3, the
      N-terminus sequence of the proteolyzed fragment was analyzed. Antibody against
      the synthetic peptide corresponding to the cleavage site specifically detected
      the fragment in the mouse forestomach extract.

PMID- 14646219
TI  - Arabidopsis ZIM, a plant-specific GATA factor, can function as a transcriptional
      activator.
AB  - Arabidopsis ZIM is a putative transcription factor containing an atypical GATA
      type zinc-finger motif. Transcriptional activation by ZIM was tested using a
      transient GAL4 fusion assay and measuring the expression of a luciferase reporter
      in tobacco BY-2 cells. ZIM functioned as a transcriptional activator, and the
      transactivation domain was found to occur in its N-terminal acidic region.

PMID- 14646220
TI  - Inhibitory activities of aromatic amino acid esters and peptides against
      ovalbumin permeation through Caco-2 cell monolayers.
AB  - Trp, Phe, and Tyr ethyl esters and their dipeptides with Gly at the C-terminals
      inhibited ovalbumin (OVA) permeation through Caco-2 monolayers. The inhibitory
      activity of Trp ethyl ester was the highest at near the concentration of 10(-6)
      M. It was suggested that Trp ethyl ester inhibited transcellular permeation of
      OVA.

PMID- 14646221
TI  - Effects of beta-casomorphin-5 on passive avoidance response in mice.
AB  - The effects of intracerebroventricular (i.c.v.) injection of bovine beta
      casomorphin-5 (beta-CM-5: Tyr-Pro-Phe-Pro-Gly), a micro-opioid agonist derived
      from milk beta-casein, on step-down type passive avoidance tasks were
      investigated in mice. Intracerebroventricular administration of a high dose (10
      microg) of beta-CM-5 produced a significant decrease in step-down latency. beta
      Funaltrexamine (5 microg, i.c.v.) almost completely reversed the beta-CM-5
      induced shortening of step-down latency, although neither naltrindole (5 ng,
      i.c.v.) nor nor-binaltorphimine (5 microg, i.c.v.) had any significant influence
      on the effect of beta-CM-5. Meanwhile, a low dose (0.5 microg, i.c.v.) of beta-CM
      5 inhibited scopolamine (1 mg/kg)-induced impairment of passive avoidance
      response. These results indicated that a high dose of beta-CM-5 induces amnesia,
      whereas a low dose ameliorates scopolamine-induced amnesia.

PMID- 14646222
TI  - Induction of apoptosis through the activation of SAPK/JNK followed by the
      expression of death receptor Fas in X-irradiated cells.
AB  - A post-irradiation treatment of the human leukemia cell line MOLT-4 with the
      antioxidant Trolox attenuated caspase-3 dependent apoptosis. The increase in the
      p53 expression and SAPK/JNK activation after X irradiation was also inhibited by
      a Trolox treatment, but the expression of BCL-2 and BAX, which would occur
      downstream from p53, was not changed. Studies on the effects of the intracellular
      calcium chelator BAPTA-AM on the induction of apoptosis and the activation of
      SAPK/JNK and caspase-3 proved that the chelation of calcium merely delayed the
      onset of radiation-induced apoptosis and the activation of SAPK/JNK and caspase
      3. When the effects of the protein synthesis inhibitor cycloheximde on the
      apoptotic signaling pathways, including the activation of caspase family proteins
      and SAPK/JNK, were investigated, the expression of death receptor Fas through
      SAPK/JNK activation was found to be required for radiation-induced apoptosis.
      Finally, the relationship between the amounts of DNA dsb and induction of
      apoptosis was examined by irradiating BrdU-incorporated cells. An increase in DNA
      dsb caused by BrdU was found, but the induction of apoptosis was not enhanced.
      From these data, we could get no positive evidence for DNA as a target of X-rays
      and p53 as an indispensable factor to induced apoptosis in X-irradiated MOLT-4
      cells.

PMID- 14646223
TI  - Melatonin protects rat liver against irradiation-induced oxidative injury.
AB  - The aim of this study was to investigate the antioxidant roles of different doses
      of melatonin (5 and 10 mg x kg (-1) ) against gamma-irradiation-caused oxidative
      damage in liver tissue after total body irradiation (TBI) with a single dose of
      6.0 Gy. Fifty adult rats were divided into 5 equal groups, 10 rats each. Groups I
      and II were injected with 5 and 10 mg x kg (-1) of melatonin, and group III was
      injected with an isotonic NaCl solution. Group IV was injected with only 5 mg x
      kg (-1) of melatonin. Group V was reserved as a sham control. Following a 30-min
      period, 6.0 Gy TBI was given to groups 1, 2 and 3 in a single fraction. The liver
      malondialdehyde (MDA) levels, super oxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) activities were measured in all groups. TBI resulted in a
      significant increase in the liver tissue MDA levels and a decrease of SOD and GSH
      Px activities. The results demonstrated that the liver tissue MDA levels in
      irradiated rats that were pretreated with melatonin (5 or 10 mg x kg (-1) ) were
      significantly decreased, while the SOD and GSH-Px activities were significantly
      increased. Decreasing the MDA levels by melatonin was dose dependent, but the
      liver tissue SOD and GSH activities were not. The data obtained in this study
      suggest that melatonin administration prior to irradiation may prevent liver
      damage by irradiation.

PMID- 14646224
TI  - The influence of split doses of gamma-radiation on human erythrocytes.
AB  - Human erythrocyte suspensions in an isotonic Na-phosphate buffer, pH 7.4, of
      hematocrit of 2% were exposed under air to gamma radiation at a dose rate of 2.2
      kGy. Erythrocytes were irradiated with single doses, and identical doses split
      into two fractions with an interval time of 3.5 h between following exposures.
      The obtained results indicated that the irradiation of enucleated human
      erythrocytes with split doses caused a reduction of hemolysis (2.4 times), a
      decrease in the level of damage to membrane lipids and the contents of MetHb,
      compared with identical single doses. However, the splitting of radiation doses
      did not change the level of damage to the membrane proteins, as was estimated
      with a maleimide spin label. The obtained results suggest that a decrease in the
      level of damage to lipids was related to a decrease in hemolysis.

PMID- 14646225
TI  - Effects of the nerve growth factor on the survival and wound healing in mice with
      combined radiation and wound injury.
AB  - High dose of ionizing radiation could cause bone-marrow aplasia and delay wound
      healing. Nerve growth factor (NGF) has been demonstrated to play roles in wound
      healing and to affect the functional activities of mature immune and
      hematopoietic cells. In this study, we investigated the effects of NGF on
      survival and wound healing in mice with combined radiation and wound injury.
      Immunohistochemical analysis indicated that the expression of NGF decreased
      significantly at postwounding days 3, 5, 7, 10 and 14 in wounded tissues combined
      with total body irradiation of 5 Gy. NGF significantly increased the survival and
      migration of skin fibroblasts with the irradiation of 15 Gy in in vitro
      experiments. Intraperitoneal and topical applications of NGF increased the
      survival rate, peripheral white blood cells and bone-marrow nucleated cells; they
      also promoted wound healing and increased the cell number of fibroblasts and
      blood capillaries in granulation tissues. These results showed evidence that NGF
      could increase wound healing and promote survival in irradiated animals. This
      dual effect of NGF may provide a new tool for the treatment of radiation-combined
      injuries.

PMID- 14646226
TI  - Response of DNA repair enzymes in murine fibrosarcoma, lymphosarcoma and ascites
      cells following gamma irradiation.
AB  - The response of different tumours to radiation varies. This variation has been
      attributed to, among others, varying DNA repair capabilities The response of
      three tumour lines, differing in their sensitivities to radiation, namely, murine
      fibrosarcoma, lymphosarcoma and ascites, was studied by following the activities
      of enzymes known to be involved in DNA repair. The activities of poly (ADP
      ribose) polymerase (PARP), DNA polymerase b and DNA ligase in fibrosarcoma,
      lymphosarcoma and ascites recorded varying degrees of increase following gamma
      irradiation (2 Gy). The increase was more pronounced in fibrosarcoma, which
      recorded a maximum 2 h after irradiation for b polymerase, and at 4 h for ligase
      and PARP, thereafter declining to near normal levels after 24 h. In contrast, the
      activity of DNA Topoisomerase I declined, corresponding to an increase in the
      PARP activity. The maximum increase in the activity of beta polymerase, ligase
      and PARP from lymphosarcoma and ascites was observed 2 h after irradiation with a
      corresponding decrease in Topoisomerase I activity. Search for the target enzymes
      and proteins for modification by PARP in gamma -irradiated fibrosarcoma tumour
      cells revealed that nuclei, and not chromatin, were preferentially modified by
      PARP. Among the nuclear proteins, histones were found to be ribosylated. The
      enzyme topoisomerase was ribosylated by PARP in vitro, and this modification was
      found to inhibit topoisomerase activity. We speculate that a possible role of
      PARP is to coordinate the activities of other enzymes in DNA repair by
      selectively inhibiting certain enzymes by the ribosylation process.

PMID- 14646227
TI  - Radioprotective effects of citrus extract against gamma-irradiation in mouse bone
      marrow cells.
AB  - The radioprotective effects of citrus extract were investigated by using the
      micronucleus test for anticlastogenic and cell proliferation activity. A single
      intraperitoneal (i.p.) injection of citrus extract (Citrus aurantium var. amara)
      at 250, 500, 1000 mg/kg body weight 1 h prior to gamma-ray irradiation (1.5 Gy)
      reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCE(S))
      and normochromatic erythrocytes (MnNCE (S)). All three doses of citrus extract
      significantly reduced the frequencies of MnPCEs and MnNCEs in mice bone marrow
      compared to non-drug-treated irradiated control (p < 0.005-0.05). The optimum
      dose for protection in mouse was 250 mg/kg to protect mice bone marrow 2.2-fold
      against the side effects of gamma-irradiation with respect to the non-drug
      treated irradiated control. The flavonoids were contained in citrus extract,
      probably to show protective activity, and reduced the clastogenic effect of
      radiation on mice bone marrow. Therefore fruits and vegetables contain flavonoids
      to be useful as protective effects under such stress conditions as irradiation.

PMID- 14646228
TI  - Effect of extended exposure to low-dose radiation on autoimmune diseases of
      immunologically suppressed MRL/MpTn-gld/gld mice.
AB  - The purpose of this paper is to analyze the relationship between alterations of
      splenic T-cell subpopulations and the amelioration of autoimmune diseases of
      MRL/MpTn-gld/gld mice (MRL/gld mice) after extended exposure to low-dose
      radiation. After the onset of disease, 4-month-old MRL/gld mice were exposed to
      doses of 0.05, 0.2, and 0.5 Gy/day for 4 weeks (5 days/week), for total doses of
      1, 4, and 10 Gy, respectively. The MRL/gld mice that were irradiated with 0.2 and
      0.5 Gy/day showed an obvious decrease in the proportion of splenic CD4(-)CD8(-) T
      cells and remission of their autoimmune diseases. After the last irradiation,
      apoptotic cells were found in the white pulp of the spleen of the MRL/gld mice
      irradiated with 0.2 Gy/day, but not in the MRL/MpJ-+/+ mice (MRL/wild mice),
      which experienced a similar treatment. Before the onset of disease, 3-month-old
      MRL/gld mice subjected to 0.2 Gy/day showed a decrease in the proportion of
      splenic CD4(-)CD8(-) T cells and less remission of their autoimmune diseases than
      the 4-month-old mice. These results suggest that the accumulated CD4(-)CD8(-) T
      cells are more sensitive to radiation than other T-cell subpopulations, and that
      decreasing CD4(-)CD8(-) T cells with extended exposure to low-dose radiation
      leads to the amelioration of autoimmune disease.

PMID- 14646229
TI  - Preferential induction of mammary tumors in p53 hemizygous BALB/c mice by
      fractionated irradiation of a sub-lethal dose of X-rays.
AB  - BALB/c mice are susceptible to radiation-induced mammary tumors as well as
      lymphomas. We investigated the effects of the p53 deficient allele and of X
      irradiation on the tumor spectrum in the BALB/c background. Substantially all p53
      -/-animals died of thymic lymphomas before 36 weeks of age, while none of the p53
      +/+ animals died during that period. At this age, mortalities of p53 +/- females
      and males were 5% (1/22) and 11% (1/9), respectively, due to non-thymic lymphoma
      and sarcoma. When exposed to 4 Gy of X-irradiation, 100% (44/44) and 95% (18/19)
      of p53 +/- mice died with tumors within 36 weeks. Among these, the predominant
      cause of death was lymphoma in either sex [26/44 (59%) in females; 13/19 (68%) in
      males]; mammary adenocarcinoma (15/44, 34%) and sarcoma (3/19, 16%) were semi
      dominant in females and males, respectively. The mortalities of similarly treated
      p53 +/+ mice were 16% (5/31) in females and 17% (3/18) in males: virtually all
      deaths were due to thymic lymphomas in either sex. When exposed to 4 currency 0.7
      Gy of X-irradiation at weekly intervals, 23/23 (100%) of the p53 +/-females died
      of tumors within 36 weeks. In these animals, mammary adenocarcinoma (15/23, 65%),
      instead of lymphoma (7/23, 30%), was dominant. None of the similarly treated p53
      +/+ females developed malignant tumors during the period. Mammary adenocarcinomas
      generated in p53 +/- females exposed or non-exposed to radiation showed a
      frequent loss of the p53 wild-type allele. Hence, we provided a useful
      experimental system to study radiation-induced mammary tumors in mice.

PMID- 14646230
TI  - Radiation protection by disulfiram: protection of membrane and DNA in vitro and
      in vivo against gamma-radiation.
AB  - Disufiram (a drug used for the treatment of alcoholism) protected microsomal
      membranes and plasmid DNA against damages induced by gamma-radiation. The
      peroxidation of membrane lipids increased linearly with the radiation dose up to
      600 Gy, and the presence of disulfiram inhibited membrane lipid peroxidation as
      assayed by the presence of thiobarbituric acid reacting substances. The reduction
      of the quantity of the supercoiled (ccc) form of plasmid pBR322 DNA is directly
      related to the radiation-induced damage, particularly to DNA strand breaks. There
      was a complete protection of plasmid DNA when exposed to gamma-radiation in the
      presence of disufiram (0.1 mM) at 300 Gy. This drug also protected deoxyribose
      against damages caused by hydroxyl radicals produced by the Fenton reaction. The
      administration of DSF to mice prior to whole-body radiation exposure (4 Gy)
      resulted in a reduction of peroxidation of membrane lipids in mice liver as well
      as a decrease in radiation-induced damage to cellular DNA, as assayed by single
      cell gel electrophoresis (comet assay). The results thus suggest the possible use
      of DSF as a radioprotector.

PMID- 14646231
TI  - Comparisons of pulmonary carcinogenesis in rats following inhalation exposure to
      plutonium dioxide or X-ray irradiation.
AB  - Radiation-induced pulmonary carcinogenesis was compared in female Wistar rats
      following either inhalation exposure to alpha-emitting (239)PuO(2) aerosols,
      whole-body or thoracic X-ray irradiation. Dose-dependent survival reduction was
      correlated with increased malignant lung tumors at doses over 0.45 Gy, reaching
      the maximum incidence of 90% at 6.6-8.5 Gy in (239)Pu-exposed rats. While the
      differential dose responses for each histopathological type of tumors were noted,
      almost 70-80% were carcinomas among all of the primary tumors from (239)Pu
      exposed rats. As the dose response curves for lung carcinomas were compared, the
      slope of the fit linear equation and the calculated relative effectiveness for
      50% incidence of lung carcinomas were approximately 11-times as high in (239)Pu
      exposure as those of thoracic X-irradiation. The numbers of tumor lesions
      distributed in the lung per tumor-bearing animal were about 2-fold more in
      (239)Pu-exposed rats, while the proportions of their histopathological types were
      similar between (239)Pu-exposure and X-irradiation. These results indicate that
      the magnitudes of the relative effectiveness or risk for pulmonary carcinogenesis
      are greater in (239)Pu-exposure than X-irradiation, and that radiation-induced
      lung tumors appear to originate mostly from the same target epithelial cells.

PMID- 14646232
TI  - Efficient repair of DNA damage induced by heavy ion particles in meiotic prophase
      I nuclei of Caenorhabditis elegans.
AB  - The effects of heavy ion particle irradiation on meiosis and reproductive
      development in the nematode Caenorhabditis elegans were studied. Meiotic
      pachytene nuclei are significantly resistant to particle irradiation by the heavy
      ions carbon and argon, as well as to X-rays, but not UV, whereas diplotene to
      diakinesis stage oocytes and early embryonic cells are not. Chromosomal
      abnormalities appear in mitotic cells and in maturing oocytes irradiated with
      heavy ion particles during the diplotene to the early diakinesis stages, but not
      in oocytes irradiated during the pachytene stage. The pachytene nuclei of ced-3
      mutants, which are defective in apoptosis, are similarly resistant to ionizing
      radiation, but pachytene nuclei depleted for Ce-atl-1 (ataxia-telangiectasia like
      1) or Ce-rdh-1/rad-51 are more sensitive. Pachytene nuclei thus appear to
      effectively repair heavy ion-induced DNA damage by the meiotic homologous
      recombination system.

PMID- 14646233
TI  - 137Cs soil-to-plant transfer for individual species in a semi-natural grassland.
      Influence of potassium soil content.
AB  - In the present study we assessed the radiocaesium uptake by plants in order to
      piece together information on factors affecting the uptake processes,
      particularly K supply and plant species differences. Vegetation uptake from soil
      contaminated by the Chernobyl accident was compared at two semi-natural
      grasslands. The Cs/K discrimination factor (DF), which is often used to evaluate
      a plant's efficiency in absorbing nutrients from soil, was estimated. The
      obtained DF values (0.01 to 0.8) vary with K soil concentrations and plant
      species, indicating that the (40)K is more efficiently absorbed than (137)Cs. The
      soil-to-plant relationship was evaluated by means of the transfer factor (TF).
      The (137)Cs TF(sp) values obtained from separated plant species varied within the
      range of 0.016 to 0.400 (site 1) and 0.017 to 0.171 (site 2). When mixed grass
      samples were considered a large variation was observed, mainly for site 1. The
      (137)Cs TF(mix) ranges were: 0.018 to 0.250 for site 1 and 0.017 to 0.167 for
      site 2. These values fall within the range of TFs commonly reported (0.0001-1).
      Our present data suggest that these pastures are apt for forage use. Different
      plant species presented different individual behavior regarding their (137)Cs
      TF(sp) when the (40)K soil activity concentration was taken in account. For most
      of the species analyzed, we observed a gradual decrease in the individual (137)Cs
      TF(sp) when the (40)K soil activity concentration was increased, with the
      exception of Taraxacum officinale at one of the sampling sites.

PMID- 14646234
TI  - natural background radiation dosimetry in the highest altitude region of Iran.
AB  - The natural background radiation has been measured in one of the highest altitude
      regions (Zagros Mountains), Chaharmahal and Bakhtiari province, in the south west
      of Iran. The outdoors-environmental monitoring exposure rate of radiation was
      measured in 200 randomly chosen regions using portable Geiger-Muller and
      scintillation detectors. Eight measurements were made in each region and an
      average value was used to calculate the exposure rate from natural background
      radiation. The average exposure rate was found to be 0.246 microGy/h and the
      annual average effective dose equivalent was found to be 0.49 mSv. An overall
      population-weighted mean outdoor dose rate was calculated to be 49 nGy/h, which
      is higher than the world-wide mean value of 44 nGy/h, as reported by UNSCEAR in
      1998, and is comparable to the annual effective dose equivalent of 0.38 mSv. A
      good correlation between the altitude and the exposure rate was observed, as the
      higher altitude regions have higher natural background radiation levels.

PMID- 14646235
TI  - Uranium concentration in typical Pakistani diet.
AB  - To strengthen the radiation protection infrastructure in Pakistan, the uranium
      concentration in daily diet was measured and its associated radiation risks were
      estimated for the adult population. Food samples were collected from major cities
      and districts of the country by the market basket method, from which daily diets
      were prepared. These diet samples were analyzed using inductively coupled plasma
      mass spectrometry (ICP-MS) at the National Institute of Radiological Sciences,
      Japan, the regional Central Reference Laboratory of the Reference Asian Man
      Project. The measured values of the uranium content were found to vary from 2.3
      ng (g dry)(-1) to 11 ng (g dry)(-1). The geometric mean concentration and
      geometric standard deviation were 4.5 x//1.7 ng (g dry)(-1). This leads to a
      daily dietary intake of 2.6 x// 1.7 microg d(-1) or 33 x// 1.7 mBq d(-1), which
      is approximately 40% higher than the ICRP value. The measured value, i.e. 33 mBq
      d(-1), contributes 12 Bq y(-1) to annual intake of 238U activity and 0.54 microSv
      to the committed effective dose to the adult population. This is a very small
      fraction of the ICRP annual effective dose limit of 1 mSv for the general public.
      Therefore, it would pose no significant health hazard.

PMID- 14646237
TI  - Optical bioimaging: from living tissue to a single molecule: imaging and
      functional analysis of blood flow in organic microcirculation.
AB  - Activity of blood cells, erythrocytes, leucocytes, and platelets, in
      microcirculation was observed by using an intravital microscope and confocal
      laser scanning microscope connected with an image processing system including
      fluorescence and phosphorescence emission methods. Dynamic functions of the blood
      flow were mainly observed in mesentery, brain, and liver tissues of rats. The
      results are summarized as follows: Deformability of diabetic erythrocytes was
      significantly lower than that of healthy controls, particularly at high shear
      rate. The spring constant and Young's modulus of diabetic erythrocytes obviously
      stiffened, making them hard to deform in the capillary. During hemorrhagic shock
      and thrombosis, flow velocity and oxygen partial pressure of blood decreased in
      the brain and liver tissues that can be visualized by using FITC stained
      erythrocytes and Pd-porphyrin derivative as a pO(2) probe. Platelet adhesion and
      thrombus formation in the micro-vessels accelerated under the photodynamic
      reaction; diabetic platelets showed augmented adhesion and aggregation on the
      vessel wall which was followed by acute thromboembolism. Active oxygen radicals
      take part in thrombus formation, accompanied with adhesion of the activated
      leucocytes. Fluorescent dye probes, rhodamine G and acridine orange, are quite
      useful for visualization of the flow behavior of platelets and leucocytes,
      respectively.

PMID- 14646238
TI  - Optical bioimaging: from living tissue to a single molecule: optical detection of
      synaptically induced glutamate transporter activity in hippocampal slices.
AB  - Since voltage-sensitive dyes (VSDs) change their optical properties in response
      to membrane potential changes, non-invasive optical measurements of membrane
      excitation using VSDs have been applied to various types of excitable tissue.
      This article deals with the authors' recent work using this technique in addition
      to basic and technical information about VSD imaging. By applying this technology
      to hippocampal brain slices, we have found that astrocytes play indispensable
      roles in sequestering glutamate, maintenance of synaptic transmission, and
      neuronal survival. Finally, the potential of VSD imaging for drug development was
      discussed.

PMID- 14646239
TI  - Optical bioimaging: from living tissue to a single molecule: calcium imaging in
      blood vessel in situ employing two-photon excitation fluorescence microscopy.
AB  - Recent developments in optoelectronics permit real-time Ca(2+) imaging of thin
      planes within cells utilizing laser scanning confocal microscopy (LSCM). However,
      a major complication associated with this imaging system involves increased
      phototoxicity with improved spatiotemporal resolution. Two-photon excitation
      microscopy (TPEM) helps to minimize phototoxicity due to the restriction of this
      technique to the volume proximal to the geometric focus of the light. In this
      study, the capability of Ca(2+) imaging was investigated employing recently
      developed real-time TPEM, RTS2000MP (Bio-Rad, Tokyo) with a mode-locked Ti
      sapphire laser. Z-axis resolution of RTS2000MP with high NA objectives defined as
      full-width at half maximum (FWHM) with a 0.5-microm fluorescent bead provided
      values nearly identical to those obtained with LSCM at a small pinhole (0.2 mm)
      (approximately 0.6 microm). When serial sectioning of 21 sequential images at 0.3
      microm intervals in cultured endothelial cells loaded with calcein and
      tetramethyl-rhodamine methylester were performed with TPEM, the z-axis resolution
      was higher than that observed with LSCM; moreover, the photobleaching rate was
      significantly lower than that obtained with LSCM. Maximum fluorescence
      intensities were detected at 780 nm in excitation spectra of fluo-3 and fluo-4
      Ca(2+)-sensitive probes with TPEM. Fluorescence images in mouse arterial
      endothelial cells loaded with fluo-4 could be clearly visualized by TPEM in situ.
      Application of acetylcholine caused oscillatory increase in [Ca(2+)](i) of
      endothelial cells; subsequently, relaxation along the major axis of smooth muscle
      cells was evident. Furthermore, consecutive long-lasting experiments could be
      repeated with identical response in the same microscopic field. In conclusion,
      fluorescence imaging employing TPEM is useful for Ca(2+) imaging in blood vessels
      in situ.

PMID- 14646240
TI  - Optical bioimaging: from living tissue to a single molecule: atrio-ventricular
      difference in myocardial excitation-contraction coupling--sequential versus
      simultaneous activation of SR Ca2+ release units.
AB  - Rapid-scanning cofocal microscopy has been applied to the analysis of early phase
      Ca(2+) transients in ventricular and atrial cardiomyocytes. On electrical
      stimulation of ventricular myocytes, Ca(2+) concentration begins to rise earliest
      at the Z-line level and becomes uniform throughout the cytoplasm within about 10
      ms after the onset of the action potential; transsarcolemmal Ca(2+) influx
      triggers Ca(2+) release from release sites on the junctional sarcoplasmic
      reticulum (SR) coupled to T-tubules at the Z-line throughout the cytoplasm. In
      atrial myocytes lacking the T-tubular network, transsarcolemmal Ca(2+) influx
      during an action potential triggers SR Ca(2+) release only at subsarcolemmal
      region. SR Ca(2+) release then spreads towards the central region of the cell
      through a propagated Ca(2+)-induced-Ca(2+) release mechanism. The atrio
      ventricular difference in excitation-contraction coupling mechanisms underlies
      some of the atrio-ventricular difference in response to physiological and
      pharmacological stimuli.

PMID- 14646241
TI  - Optical bioimaging: from living tissue to a single molecule: single-molecule
      visualization of cell signaling processes of epidermal growth factor receptor.
AB  - Single-molecule imaging is an ideal technology to study molecular mechanisms of
      biological reactions in vitro. Recently, this technology has been extended to
      real-time observation of fluorescent dye-labeled molecules in living cells. Total
      internal reflection fluorescence microscopy is the major technique for this
      purpose. Using this technique, we have studied the process of early signal
      transduction of epidermal growth factor (EGF) in single molecules: binding of EGF
      to its receptor (EGFR) on the cell surface, dimerization of EGFR induced by
      binding of EGF, fluctuation of the structure of EGFR clusters, activation of EGFR
      through tyrosine phosphorylations on its cytoplasmic domain, and recognition of
      activated EGFR by a cytoplasmic adaptor protein, Grb2. EGF induces intracellular
      calcium response, sometimes caused by less than one hundred EGF molecules. Single
      molecule studies suggested that this highly sensitive response to EGF was due to
      the amplification of the EGFR signal using dynamic clustering, reorganization of
      the dimers, and lateral mobility of EGFR on the cell surface. Through these
      studies, single-molecule analysis has proven to be a powerful technology to
      analyze intracellular protein systems.

PMID- 14646242
TI  - Modulation of 8-OH-DPAT-induced hypothermia by imipramine in rats.
AB  - The effects of imipramine on 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT),
      the 5-hydroxytryptamine (5-HT)(1A)-receptor full agonist, -induced hypothermia
      was examined in rats. Single administration of imipramine (30 mg/kg, i.p.)
      attenuated 8-OH-DPAT-induced hypothermia. This effect of imipramine was blocked
      by the 5-HT(2A)-receptor antagonist ketanserin. 8-OH-DPAT-induced hypothermia was
      not altered 24 h after repeated administration of imipramine (1 - 10 mg/kg per
      day) for 14 days. However, 8-OH-DPAT-induced hypothermia was significantly
      enhanced in repeated imipramine (10 mg/kg per day)-treated rats that received 8
      OH-DPAT plus imipramine 24 h after the final imipramine administration for 14
      days. The 5-HT(2A)-receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      ((+/-)-DOI) attenuated the 8-OH-DPAT-induced hypothermia in drug naive rats. The
      inhibitory effect of (+/-)-DOI (0.3 mg/kg, s.c.) on 8-OH-DPAT-induced hypothermia
      was attenuated by repeated administration of imipramine (10 mg/kg per day) for 14
      days. These findings suggest that enhancement of the 5-HT(1A) receptors by
      repeated administration of imipramine may be due to reduction of the inhibitory
      effects from the 5-HT(2A) receptors to the 5-HT(1A) receptors.

PMID- 14646243
TI  - cGMP inhibits GTP cyclohydrolase I activity and biosynthesis of
      tetrahydrobiopterin in human umbilical vein endothelial cells.
AB  - Tetrahydrobiopterin (BH4) acts as an essential cofactor for the enzymatic
      activity of nitric oxide (NO) synthases. Biosynthesis of the cofactor BH4 starts
      from GTP and requires 3 enzymatic steps, which include GTP cyclohydrolase I (GCH
      I) catalysis of the first and rate-limiting step. In this study we examined the
      effects of cGMP on GCH I activity in human umbilical vein endothelial cells under
      inflammatory conditions. Exogenous application of the cGMP analogue 8-bromo-cGMP
      markedly inhibited GCH I activity in the short term, whereas an cAMP analogue had
      no effect on GCH I activity under the same condition. NO donors, NOR3 and sodium
      nitroprusside, elevated the intracellular cGMP level and reduced GCH I activity
      in the short term. This inhibition of GCH I activity was obliterated in the
      presence of an NO trapper carboxy-PTIO. NO donors had no effect on GCH I mRNA
      expression in the short term. Moreover, cycloheximide did not alter the
      inhibition by NO donors of GCH I activity. These findings suggest that
      stimulation of the cGMP signaling cascade down-regulates GCH I activity through
      post translational modification of the GCH I enzyme.

PMID- 14646244
TI  - Amyloid beta peptide specifically promotes phosphorylation and nuclear
      translocation of the extracellular signal-regulated kinase in cultured rat
      cortical astrocytes.
AB  - To explore cellular signaling molecules that respond to amyloid beta protein (A
      beta), we investigated the effect of A beta on tyrosine phosphorylation of
      cellular proteins in cultured rat cortical astrocytes. Western blotting with the
      phosphotyrosine-specific monoclonal antibody 4G10 demonstrated that exposure of
      cultured rat cortical astrocytes to 20 microM A beta 1-40 or A beta 25-35 for 24
      h resulted in a prominent increase in the phosphotyrosine content of 44-kDa
      protein. The A beta-induced increase in tyrosine phosphorylation of 44-kDa
      protein was blocked by U0126, a specific inhibitor of the extracellular signal
      regulated kinase (ERK) kinase MEK. Western blotting with anti-phospho-ERK1/2
      antibody and anti-ERK1/2 antibody demonstrated that A beta 1-40 or A beta 25-35
      induced an increase in the dually (tyrosine and threonine) phosphorylated form of
      ERK1 and ERK2, with no change in total ERK1/2 level. In addition,
      immunofluorescent staining with anti-ERK1/2 antibody revealed that A beta induced
      a significant increase in the number of cells expressing ERK1/2 mainly in the
      nucleus. These results suggest that A beta specifically promotes tyrosine
      phosphorylation and nuclear translocation of ERK in astrocytes.

PMID- 14646245
TI  - Ca2+-releasing effect of cerivastatin on the sarcoplasmic reticulum of mouse and
      rat skeletal muscle fibers.
AB  - We analyzed the effect of HMG-CoA reductase inhibitors on Ca(2+) release from the
      sarcoplasmic reticulum (SR) using chemically skinned skeletal muscle fibers from
      the mouse and the rat. Cerivastatin (>20 microM) released Ca(2+) from the SR,
      while pravastatin showed only a little effect. The rates of Ca(2+) release were
      increased by cerivastatin at all Ca(2+) concentrations tested. Cerivastatin
      induced Ca(2+) release in the presence of Ca(2+) was affected by adenosine
      monophosphate, Mg(2+), and procaine in essentially the same way as for caffeine
      induced Ca(2+) release. The Ca(2+)-uptake capacity of the SR was reduced after co
      treatment with ryanodine and cerivastatin at pCa 6.0 to a much greater extent
      than with ryanodine alone. Thus, cerivastatin-induced Ca(2+) release in the
      presence of Ca(2+) must be a result of the activation of the Ca(2+)-induced
      Ca(2+) release (CICR) mechanism of the ryanodine receptor. However, even when
      CICR was maximally inhibited by Mg(2+) and procaine, or in the practical absence
      of Ca(2+) (pCa >8), cerivastatin still caused Ca(2+) release. These results
      indicate that cerivastatin causes Ca(2+) release also by activating some other
      mechanism(s) in addition to the activation of CICR. Either or both of these
      effects might be related to its adverse effect, rhabdomyolysis.

PMID- 14646246
TI  - Effects of KRN4884, a novel K+ channel opener, on ionic currents in rabbit
      femoral arterial myocytes.
AB  - Effects of KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3
      pyridinecarboxamidine), a novel K(+) channel opener, on ionic currents were
      examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp
      conditions where cells were superfused with 5.9 mM K(+) bathing solution, KRN4884
      elicited an outward current at -30 mV. KRN4884-induced current had a reversal
      potential of -78 mV and was abolished by application of glibenclamide (glib).
      KRN4884 was approximately 43 times more potent than levcromakalim in activating
      an ATP-sensitive K(+) current (I(K-ATP)). On the other hand, KRN4884 affected
      neither voltage-dependent Ca(2+) nor delayed rectifier K(+) channel currents. In
      the inside-out patch clamp configuration where cells were superfused with the
      symmetrical 140 mM K(+) solution, KRN4884 activated 47 pS K(+) channels in the
      presence of adenosine diphosphate. Similar 47 pS K(+) channels, which were
      reversibly inhibited by glib, were recorded under outside-out patch conditions.
      Using RT-PCR analysis, we found that inward rectifier K channel 6.1 (Kir6.1) and
      sulfonylurea 2B (SUR2B) transcripts were predominantly expressed in rabbit
      femoral artery. These results indicate that KRN4884 potently activates I(K-ATP)
      in RFAMs. The KRN4884-sensitive 47 pS K(+) channel activity underlying I(K-ATP)
      is a vascular type K(ATP) channel consisting of Kir6.1 and SUR2B and has similar
      characteristics to those of ATP-sensitive K(+) channels activated by K(+) channel
      openers in other types of smooth muscles.

PMID- 14646247
TI  - Intrathecal treatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine blocks
      the antinociception induced by endomorphin-1 and endomorphin-2 given
      intracerebroventricularly in the mouse.
AB  - The involvement of spinopetal noradrenergic and serotonergic systems in
      antinociception induced by endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given
      supraspinally or spinally were investigated in male CD-1 mice. Groups of mice
      were pretreated intrathecally (i.t.) with 6-hydroxydopamine (6-OHDA, 20 microg)
      or 5,7-dihydroxytryptamine (5,7-DHT, 50 microg) for 3 days before
      intracerebroventricular (i.c.v.) or i.t. injection of different doses of EM-1 or
      EM-2, and the tail-flick response was measured for antinociceptive effects. I.t.
      pretreatment with 6-OHDA for 3 days, which markedly depleted noradrenaline (NA)
      contents by more than 90%, but not serotonin (5-HT) in the spinal cord,
      completely abolished the antinociception induced by i.c.v.-administered EM-1 or
      EM-2. Intrathecal pretreatment with 5,7-DHT for 3 days, which markedly reduced 5
      HT contents by more than 92%, but only reduced NA by 14 - 25% in the spinal cord,
      also markedly attenuated the antinociception induced by i.c.v.-administered EM-1
      or EM-2. However, the antinociception induced by i.t.-administered EM-1 or EM-2
      was not affected in either 6-OHDA or 5,7-DHT pretreated mice. It is concluded
      that NA and 5-HT in the spinal cord are involved in the antinociception induced
      by supraspinally, but not spinally administered EM-1 and EM-2.

PMID- 14646248
TI  - Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and
      inhibits in vitro contraction of airway smooth muscle.
AB  - Propolis is a bee product, which has long been used in folk medicine for the
      management of different diseases. In this study we evaluated the analgesic and
      anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis
      (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg
      inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7
      mg. kg(-1). In the formalin test, the extract caused a significant reduction in
      pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and
      for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/
      0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice;
      however, this extract was ineffective when assessed in the tail-flick and hot
      plate thermal assays. The analgesic effect of Et-Blg was associated with the
      inhibition of inflammatory responses and not to a simple irritation of nervous
      terminals. In vitro, this extract inhibited the contraction of trachea smooth
      muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50)
      = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and
      carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).

PMID- 14646249
TI  - Irsogladine prevents monochloramine-induced gastric mucosal lesions by improving
      the decrease in mucosal blood flow due to the disturbance of nitric oxide
      synthesis in rats.
AB  - The inhibitory effect of an anti-ulcer drug irsogladine [2,4-diamino-6-(2,5
      dichlorophenyl)-s-triazine maleate] on monochloramine (NH(2)Cl)-induced gastric
      mucosal lesions and its mechanisms of action were clarified in rats. Irsogladine
      dose-dependently prevented the formation of gastric mucosal lesions induced by 60
      mM NH(2)Cl. The mucosal protective effect of irsogladine was not influenced by
      capsaicin-sensitive sensory defunctionalization. On the other hand, its
      protective effect was diminished by the inhibitor of nitric oxide synthase N(G)
      nitro-L-arginine methylester (L-NAME), but not by the inducible nitric oxide
      synthase selective inhibitor aminoguanidine. Irsogladine restored the NH(2)Cl
      induced decrease in the gastric cGMP formation as an index of nitric oxide
      synthesis, while it alone had no influence on the cGMP formation in intact
      tissues. Pretreatment with L-NAME abolished the recovery of cGMP by irsogladine.
      Furthermore, irsogladine ameliorated the NH(2)Cl-induced decrease in gastric
      mucosal blood flow, which was also reversed by pretreatment with L-NAME. These
      findings suggest that the improvement of the decrease in mucosal blood flow
      subsequent to the disturbance of gastric nitric oxide synthesis is involved in
      the protective effect of irsogladine on gastric mucosal lesions caused by
      NH(2)Cl.

PMID- 14646250
TI  - Roxatidine- and cimetidine-induced angiogenesis inhibition suppresses growth of
      colon cancer implants in syngeneic mice.
AB  - Cimetidine is known to suppress the growth of several tumors, including
      gastrointestinal cancer, in humans and animals. Nonetheless, whether other
      histamine H(2)-receptor antagonists exert such tumor suppressive effects remains
      unclear. The effect of roxatidine acetate hydrochloride (roxatidine), an H(2)
      receptor antagonist, on the growth of colon cancer implanted in mice was examined
      and compared with that of cimetidine. Drugs were orally delivered for 26 - 29
      days beginning before or after implantation of syngeneic colon cancer (Colon 38)
      in C57BL/6 mice. Tumor volume was determined throughout and histochemical
      analysis was also performed. Tumor tissue and serum vascular endothelial growth
      factor (VEGF) levels were measured. In vitro cell growth was assessed by the MTT
      assay. Both roxatidine and cimetidine significantly suppressed the growth of
      Colon 38 tumor implants. Histologic analysis revealed that such antagonists
      markedly increased necrotic areas and decreased the density of microvessels in
      tumor tissue. Both H(2)-receptor antagonists suppressed VEGF levels in tumor
      tissue and significantly decreased serum VEGF levels in Colon 38-bearing mice.
      Such drugs, however, failed to suppress in vitro growth of the cell line. In
      conclusion, both roxatidine and cimetidine were found to exert suppressive
      effects on the growth of colon cancer implants in mice by inhibiting angiogenesis
      via reducing VEGF expression.

PMID- 14646251
TI  - Protective effects of kakkalide from Flos puerariae on ethanol-induced lethality
      and hepatic injury are dependent on its biotransformation by human intestinal
      microflora.
AB  - When kakkalide, which was isolated from Flos Puerariae, was incubated with human
      fecal bacteria, kakkalide was metabolized to irisolidone via kakkalidone. When
      kakkalide (250 mg/kg) was orally administered to rats, irisolidone, but not
      kakkalide, was detected in the blood. The mortality associated with ethanol
      treatment was slightly reduced when the mice were intraperitoneally treated with
      kakkalide. Intraperitoneally administered kakkalide and kakkalidone did not
      reduce alcohol toxicity. However, orally administered kakkalide and
      intraperitoneally administered irisolidone significantly reduced the mortality.
      Orally administered kakkalide and intraperitoneally injected irisolidone greatly
      reduced serum alanine aminotransferase and aspartate aminotransferase activities
      in ethanol-intoxified mice. Orally administered kakkalide and intraperitoneally
      administered irisolidone significantly lowered the level of blood ethanol. The
      results indicate that kakkalide is a prodrug of irisolidone in protecting against
      ethanol-induced lethality and hepatic injury.

PMID- 14646252
TI  - Protective effect of teprenone against acute gastric mucosal lesions induced by
      compound 48/80, a mast cell degranulator, in rats.
AB  - The protective effect of teprenone, an anti-ulcer drug, against acute gastric
      mucosal lesions was examined in rats with a single intraperitoneal injection of
      compound 48/80 (0.75 mg/kg). Teprenone (50, 100, or 200 mg/kg) was orally
      administered 0.5 h before compound 48/80 treatment. Administered teprenone
      prevented gastric mucosal lesion development found at 3 h after compound 48/80
      treatment dose-dependently, although no dose of teprenone affected the decreased
      gastric mucosal blood flow and increased serum serotonin and histamine
      concentrations found at 3 h after the treatment. Increases in the activities of
      myeloperoxdiase (an index of neutrophil infiltration) and xanthine oxidase and
      the content of thiobarbituric acid reactive substances (an index of lipid
      peroxidation) and decreases in the contents of hexosamine (a marker of gastric
      mucus) and adherent mucus occurred in gastric mucosal tissues at 3 h after
      compound 48/80 treatment. Administered teprenone dose-dependently attenuated all
      these changes found at 3 h after compound 48/80 treatment. These results indicate
      that orally administered teprenone protects against compound 48/80-induced acute
      gastric mucosal lesions in rats possibly through its stimulatory action on
      gastric mucus synthesis and secretion and its inhibitory action on neutrophil
      infiltration and enhanced lipid peroxidation in the gastric mucosal tissue.

PMID- 14646253
TI  - Evaluation of human peroxisome proliferator-activated receptor (PPAR) subtype
      selectivity of a variety of anti-inflammatory drugs based on a novel assay for
      PPAR delta(beta).
AB  - The nuclear receptor PPAR (peroxisome proliferator-activated receptor) has three
      subtypes named alpha, delta(beta), and gamma that may act as receptors for a
      range of compounds including antihyperglycaemic drugs, insulin sensitizers, and
      non-steroidal anti-inflammatory drugs (NSAIDs). Although profiling of the subtype
      selectivity of the compounds for PPAR is indispensable to elucidate their
      pharmacological action, the absence of an appropriate transactivation assay for
      PPAR delta led us to develop a sensitive and reproducible method. We found that
      co-expression of PPAR delta, retinoid X receptor (RXR) alpha, and coactivators
      such as CBP and SRC-1 enhanced basal and agonist-dependent activation of PPAR
      responsive element (PPRE)-driven transcription by PPAR delta, rendering a PPRE
      driven reporter assay reliable and sensitive. Utilizing this assay for PPAR
      delta, we re-evaluated the subtype selectivity of a variety of anti-inflammatory
      drugs for human PPAR. The PPAR agonists tested included two leukotriene (LT) D(4)
      antagonist, seven NSAIDs, and two anti-rheumatoid drugs. We found that a novel
      LTD(4) antagonist, FK011 ([2-(((2-(4-tert-butyl-1,3-thiazol-2-yl)-1-benzofuran-5
      yl)oxy)methyl)phenyl]acetic acid), showed marked agonistic activity for PPAR
      gamma. NSAIDs were classified into the following three groups: those showing no
      activity for all subtypes, those that were selective for PPAR gamma such as
      indomethacin and diclofenac, and those showing agonistic activity for the delta
      and gamma subtypes such as ibuprofen. These results will be important to studies
      on the molecular mechanisms of pharmacological actions of LTD(4) antagonists and
      NSAIDs.

PMID- 14646254
TI  - Comparative pharmacological studies on the A2 adenosine receptor agonist 5'-n
      ethyl-carboxamidoadenosine and its F19 isotope labelled derivative.
AB  - Adenosine receptors are expressed in various mammalian tissues where they mediate
      the effects of adenosine on cellular functions through a number of signalling
      mechanisms. 18F-NECA is the positron-emitting derivative of the A(2)-receptor
      agonist NECA (5'-n-ethyl-carboxamidoadenosine) and is a radioligand for PET
      imaging of adenosine receptors. Contractility and relaxation studies were
      performed on guinea pig atrial myocardium, pulmonary artery, and thoracic aorta
      to compare the pharmacological effects of NECA and F-NECA (a non-emitting
      derivative) on tissues. Furthermore, the effect of NECA and F-NECA on the
      potassium conductance was investigated in DDT1 MF-2 smooth muscle cells with the
      patch-clamp technique. Both NECA and F-NECA reduced the contractile force in
      atrial myocardium and evoked phasic contraction in pulmonary artery (A(1)
      adenosine-receptor-mediated actions) in a dose dependent manner; however, the
      apparent affinity was lower for F-NECA. No difference was found in relaxation
      induced by these compounds in 1 microM noradrenaline-precontracted aorta and
      pulmonary artery (in the presence of DPCPX, an A(1) adenosine receptor
      antagonist, tissue containing A(2B) adenosine receptors). NECA (5 microM) and F
      NECA (5 microM) also decreased the peak current and accelerated activation and
      inactivation properties of the potassium channels, but F-NECA was less effective.
      These results suggest that while NECA and F-NECA are equivalent agonists of
      vascular A(2B) receptors, they mediate different changes of some parameters. When
      evaluating the data obtained by the use of radiolabelled ligands, one has to take
      into consideration the possible physiological effects of the ligands besides its
      binding properties to tissues.

PMID- 14646255
TI  - Effect of a novel potential atypical antipsychotic drug, Y-931, in producing
      dystonia in cebus monkeys.
AB  - The effect of Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)-6H-[1]benzothieno[2,3
      b][1,5]benzodiazepine maleate), a novel potential atypical antipsychotic
      candidate, in producing dystonia in Cebus monkeys was investigated. Y-931 induced
      relatively weak dystonia in several observation periods at doses greater than 0.1
      mg/kg, i.m. Although Y-931 significantly increased total dystonia scores (the sum
      of 15 to 360 min after injection) at doses greater than 0.5 mg/kg, i.m., the
      scores did not exceed 20, up to a dose of 1.0 mg/kg, i.m. and lacked a dose
      response relationship. The present result suggests that Y-931 is predicted to
      have a low risk of extrapyramidal side effects.

PMID- 14646256
TI  - Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of
      cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line
      L929.
AB  - Harpagophytum procumbens (Pedaliaceae) has been used for the treatment of pain
      and arthritis. The effect of Harpagophytum procumbens against lipopolysaccharide
      induced inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, reverse transcription-polymerase chain
      reaction, prostaglandin E(2) (PGE(2)) immunoassay, and nitric oxide detection on
      mouse fibroblast cell line L929. The aqueous extract of Harpagophytum procumbens
      was shown to suppress PGE(2) synthesis and nitric oxide production by inhibiting
      lipopolysaccharide-stimulated enhancement of the cyclooxygenase-2 and inducible
      nitric oxide synthase (iNOS) mRNAs expressions in L929 cells. These results
      suggest that Harpagophytum procumbens exerts anti-inflammatory and analgesic
      effects probably by suppressing cyclooxygenase-2 and iNOS expressions.

PMID- 14646257
TI  - Nonspecific effects of the selective kappa-opioid receptor agonist U-50,488H on
      dopamine uptake and release in PC12 cells.
AB  - kappa-Opioid receptor agonists decrease the levels of extracellular dopamine in
      vivo and in vitro. However, the mechanism(s) underlying these actions are
      unclear. The objective of this study was to distinguish between an effect of the
      selective kappa-opioid receptor agonist U-50,488H ((trans-(+/-)-3,4-dichloro-N
      methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide methanesulfonate) on
      secretion and reuptake of dopamine by PC12 cells. The data show that U-50,488H
      has both a modest effect to increase dopamine release and a more pronounced
      effect to inhibit dopamine uptake. Neither effect was sensitive to nor
      binaltorphimine or naloxone, suggesting that they are not mediated through an
      opioid receptor.

PMID- 14646258
TI  - Platonin, a cyanine photosensitizing dye, inhibits pyrogen release and results in
      antipyresis.
AB  - Intravenous injection of the supernatant fluids from human peripheral blood
      mononuclear cells (PBMC) incubated with lipopolysaccharide (LPS) caused fever in
      rabbits. The fever was in parallel with the levels of either interleukin-1 beta
      (IL-1 beta), IL-6, or tumor necrosis factor-alpha (TNF-alpha) in supernatant
      fluids. When incubating the platonin with the LPS-human PBMC, both the levels of
      IL-1 beta, IL-6, or TNF-alpha in supernatant fluids and the pyrogenicity of
      supernatant fluids were significantly suppressed. The febrile response to
      supernatant fluids from the LPS-stimulated PBMC was attenuated almost completely
      by adding anti-IL-1 beta, but not anti-IL-6 or anti-TNF-alpha, monoclonal
      antibody to supernatant fluids. In addition, both the fever and the increased
      levels of either IL-1 beta, IL-6, or TNF-alpha in rabbit serum following an
      intravenous administration of LPS were significantly attenuated by pretreatment
      with an intravenous dose of platonin. Furthermore, the fever induced by
      intravenous injection of IL-1 beta was reduced by pretreatment of rabbits with
      intravenous injection of platonin. The data indicate that platonin inhibits
      production of pyrogenic cytokines (in particular, IL-1 beta) from PBMC and
      results in antipyresis.

PMID- 14646259
TI  - Effect of bright light on EEG activities and subjective sleepiness to mental task
      during nocturnal sleep deprivation.
AB  - The purpose of this study was to investigate the effect of the exposure to bright
      light on EEG activity and subjective sleepiness at rest and at the mental task
      during nocturnal sleep deprivation. Eight male subjects lay awake in semi-supine
      in a reclining seat from 21:00 to 04:30 under the bright (BL; >2500 lux) or the
      dim (DL; <150 lux) light conditions. During the sleep deprivation, the mental
      task (Stroop color-word conflict test: CWT) was performed each 15 min in one
      hour. EEG, subjective sleepiness, rectal and mean skin temperatures and urinary
      melatonin concentrations were measured. The subjective sleepiness increased with
      time of sleep deprivation during both rest and CWT under the DL condition. The
      exposure to bright light delayed for 2 hours the increase in subjective
      sleepiness at rest and suppressed the increase in that during CWT. The bright
      light exposure also delayed the increase in the theta and alpha wave activities
      in EEG at rest. In contrast, the effect of the bright light exposure on the theta
      and alpha wave activities disappeared by CWT. Additionally, under the BL
      condition, the entire theta activity during CWT throughout nocturnal sleep
      deprivation increased significantly from that in a rest condition. Our results
      suggest that the exposure to bright light throughout nocturnal sleep deprivation
      influences the subjective sleepiness during the mental task and the EEG activity,
      as well as the subjective sleepiness at rest. However, the effect of the bright
      light exposure on the EEG activity at the mental task diminishes throughout
      nocturnal sleep deprivation.

PMID- 14646260
TI  - Examination of the factor structure of center of foot pressure movement and cross
      validity.
AB  - This study aimed to determine the factor structure of the center of foot pressure
      (CFP) movement during static upright posture, and to objectively categorize and
      summarize parameters to evaluate CFP movement. The subjects were 220 healthy
      young males and females. The measurement of CFP was carried out 3 times with 1
      min rest and the mean of trials 2 and 3 was used for the analysis. The
      measurement device was an Anima's stabilometer G5500. The data sampling frequency
      was 20 Hz. Thirty-four parameters with high reliability were selected from the
      following 6 domains except for the center position which is a fundamental
      attribute: distance, distribution of amplitude, area, velocity, power spectrum,
      and body sway vector. Factor analysis (principal factor method and promax
      rotation) was applied to a correlation matrix consisting of 32 parameters. Four
      factors abstracted were interpreted as follows; unit time sway, front and back
      sway, left and right sway and high frequency band of power spectrum. The
      reliability coefficient (ICC=0.89-0.95) and the congruence coefficient (phi=0.80
      0.97) between factors abstracted from the original and the cross-validity groups
      were very high. It was considered that the CFP movement consists of the above 4
      factors that evaluate the amount of body sway and can be synthetically evaluated
      by them.

PMID- 14646261
TI  - Seasonal effects of sleep deprivation on thermoregulatory responses in a hot
      environment.
AB  - Effects of sleep deprivation and season on thermoregulation during 60 min. of leg
      bathing (water temperature of 42 degrees C, air temperature of 30 degrees C, and
      relative humidity of 70%) were studied in eight men who completed all 4
      experiments for normal sleep and sleep deprivation in summer and winter. Rectal
      temperature (T(re)), skin temperature, total body sweating rate (M(sw-t)), local
      sweating rate on the back (M(sw-back)) and forearm (M(sw-forearm)), and skin
      blood flow on the back (SBF(back)) and forearm (SBF(forearm)) were measured. The
      changes in T(re) (DeltaT(re)) were smaller (P<0.05) for sleep deprivation than
      for normal sleep regardless of the season. This decrease in DeltaT(re) was
      significant only in summer (P<0.05). Mean skin temperature (T(mean of)(sk)) was
      higher (P<0.05) for sleep deprivation than for normal sleep regardless of the
      season. M(sw-t) was smaller (P<0.05) for sleep deprivation than for normal sleep
      regardless of season, although M(sw-back) and M(sw-forearm) were similar.
      SBF(back) and SBF(forearm) tended to be higher for sleep deprivation than normal
      sleep. The sensitivity of SBF to T(re) was higher (P<0.05) for sleep deprivation
      than for normal sleep. These data indicate that seasonal differences in
      thermoregulation were small because of morning time. Sleep deprivation increased
      dry heat loss and restrained T(re) rise, in spite of decreased sweating rate.

PMID- 14646262
TI  - Lower extremity function in terms of shock absorption when landing with
      unsynchronized feet.
AB  - The purpose of this study was to clarify the lower extremity function in terms of
      the shock absorption during unsynchronized-foot landings. The characteristics of
      the supination and pronation in the ankle joint at landing were investigated,
      assuming that the measurements of the impact force on the body could be
      demonstrated by the changes that occurred during 3 different landing motions: 
      unsynchronized-foot landings, synchronized-foot landings, and one-foot landings.
      Subjects jumped to the floor from 10-cm footstools 3 times for each type of
      landing. For the synchronized-foot landing, the rear foot angle was 92.2 degrees
      at the start of landing and did not change significantly from landing start to
      100 msec. For the one-foot landing, rear foot angle was 95.1 degrees at the start
      of landing and decreased rapidly to 87.1 degrees by 75 msec, and then increased
      rapidly to 90.8 degrees by 140 msec. For the unsynchronized-foot landing, the
      rear foot angle was 93.8 degrees at the start of the landing, decreased rapidly
      to 88.0 degrees by 75 msec, and then increased rapidly to 89.9 degrees by 115
      msec. It was clarified that the lower extremity function for the shock
      attenuation during landing with the unsynchronized-foot was similar to that with
      one-foot landings, and the lower extremity function for supporting the body after
      another foot landing was similar to that after the synchronized-foot landings in
      this study.

PMID- 14646263
TI  - Characteristics of electroencephalographic responses induced by a pleasant and an
      unpleasant odor.
AB  - More than sensory stimuli, odorous stimuli were employed to facilitate the
      evocation of emotional responses in the present study. The odor-stimulated
      emotion was evaluated by investigating specific features of encephalographic
      (EEG) responses produced thereof. In this study, the concentrations of the same
      odor were altered; viz., the changes in odor-induced emotional level were
      compared with the concurrently monitored EEG response features. In addition, we
      performed the mental task to evoke the arousal state of the brain and
      investigated the resemblance of response characteristics of the resting state to
      the post-mental task resting state. Subjects having no abnormalities in the sense
      of smell included 12 male undergraduate and graduate students (age range: 22-26
      years). Experiment I involved 2 types of odors that induced favorable odorous
      stimuli (pleasant induction); test-solutions were either diluted 150 (easily
      perceptible odorous sensation) or 500 (slightly perceptible odorous stimuli)
      times. Experiment II had 2 types of odors that evoked unfavorable odorous stimuli
      (unpleasant induction), and test-solutions with dilution rates similar to those
      of pleasant induction were prepared. Odorless distilled water was used as the
      control in both experiments. From results of rating the odorous stimuli of our
      compounds used, the candidates were respectively found to be appropriate in
      inducing the pleasant and unpleasant smell sensations. The analyses of EEG
      responses on inducing pleasant and unpleasant smell sensations revealed that the
      EEG activities of the left frontal region were enhanced. This finding may
      establish the hypothesis of a relationship prevailing between the positive
      approach-related emotion evoked by the visual sensation and the left hemisphere
      (Davidson, 1992; Tomarken et al., 1989). In other words, it can be interpreted
      that the negative withdrawal-related emotion may be associated with activities of
      the right hemisphere. However, this hypothesis may not be applicable to the
      unpleasant odors, as the unpleasant emotions are activated by the unpleasant
      odors not only in the bilateral frontal regions but also over an extensive area
      of the brain. As such, the pleasant emotions are evoked in the left frontal brain
      region while the unpleasant emotions are incited in the bilateral frontal and
      extensive regions in the brain with the odorous stimuli. Moreover, intrinsic EEG
      activities in response to the pleasant and unpleasant inputs were not observed
      after performing the mental tasks. In other words, EEG responses reflecting
      central nervous system activities elevated by loading of the mental tasks as a
      result of exposure to the pleasant and unpleasant odors may not apparently be
      observed.

PMID- 14646264
TI  - Reference norms for a fat-free mass index and fat mass index in the Japanese
      child population.
AB  - The aims of this study were to determine reference norms for a fat-free mass
      index (FFMI) and fat mass index (FMI) in a large population of healthy children
      in Japan, to observe differences in these values in three age groups between ages
      three and eleven, and to develop percentile distributions for these parameters.
      Five hundred twenty-two boys and six hundred forty-nine girls with a wide
      spectrum of stature, body mass, and body composition underwent bioelectrical
      impedance analysis (BIA) for the determination of fat-free mass (FFM) and fat
      mass (FM). Both FFM and FM were divided by stature(2) to give FFMI and FMI, as
      described previously. Normal FFMI and FMI were defined within the range of the
      25th to 75th percentile of age- and gender-specific data in this study. The
      reference norms for FFMI (3-11 yrs) were 12.7-13.4 kg/m(2) in boys and 12.0-13.0
      kg/m(2) in girls. A modest increase in boys was observed with an age increase;
      otherwise, there were no marked age differences in FFMI for the children as a
      whole. The reference norms for FMI were 2.8-3.6 kg/m(2) in boys and 3.2-3.8
      kg/m(2) in girls. For each 3-year category (i.e., ages 3-5, 6-8 and 9-11 yrs.),
      FMI progressively increased by an average of 28.6% in boys and 18.8% in girls,
      compared to an increase in BMI of 11.0 and 11.3% respectively. FFMI and FMI are
      appropriate for many purposes, and have the advantage of expressing both aspects
      of body composition in common units. In conclusion, the data presented as
      percentiles can serve as reference in comparing a child's body composition to
      that of healthy children of the same age and gender. The reference standards
      should be appropriate for almost all children in the Japan for whom stature, body
      mass, and body composition can be measured satisfactorily. However, a more
      sophisticated approach is ultimately required for evaluating body composition.
      This article is a preliminary attempt to promote future research in the area of
      childhood body composition.

PMID- 14646265
TI  - Post-exercise hyperemia after ischemic and non-ischemic isometric handgrip
      exercise.
AB  - Post-exercise related time course of muscle oxygenation during recovery provides
      valuable information on peripheral vascular disease. The purpose of the present
      study was to examine post-exercise hyperemia (forearm blood flow; FBF, Doppler
      ultrasound) assessed by peak FBF, excess FBF and the time constant for FBF
      (FBF(Tc)) following isometric handgrip exercise (IHE). Post-exercise hyperemia
      was assessed in an ischemic and non-ischemic state at different exercise
      intensities and durations. Peak FBF and excess FBF were defined as the maximum
      FBF during recovery, and the total amount of FBF volume, respectively. FBF(Tc)
      represents the time to reach approximately 37% of the change in FBF between peak
      FBF and resting FBF (delta peak FBF). Ten subjects performed IHE at "10% and 30%
      maximum voluntary contraction (MVC)" for 2 min with or without arterial occlusion
      (AO), followed by 2 min of AO alone (Study I). In Study II, six subjects
      performed 30%MVC-IHE with AO for "100%, 66%, 33% and 10% of the exhausted
      exercise duration" (time to exhaustion). In Study I, although peak FBF and excess
      FBF were significantly higher in ischemic than non-ischemic IHE for both 10% and
      30%MVC (p<0.05), FBF(Tc) was similar in the ischemic and non-ischemic conditions.
      The peak FBF, excess FBF and FBF(Tc) were all significantly higher at 30% than at
      10%MVC (p<0.05). In Study II, the peak FBF and excess FBF increased linearly
      compared to the absolute and relative exercise durations for ischemic IHE.
      FBF(Tc) increased exponentially when compared to the absolute and relative
      exercise durations. These data suggest the ischemic exercise has a larger
      hyperemic response compared to the non-ischemic exercise. In conclusion, the peak
      FBF, excess FBF and FBF(Tc) seen during post-exercise hyperemia are closely
      correlated with exercise intensity and duration, not only in non-ischemic, but
      also in the ischemic exercise. In combination with the ischemic exercise, these
      parameters could potentially prove to be valuable indicators of peripheral
      vascular disease.

PMID- 14646266
TI  - Comparison of body water turnover in endurance runners and age-matched sedentary
      men.
AB  - This study compared the body water turnover in endurance athletes and age-matched
      sedentary men. Eight competitive endurance athletes (20.8+/-1.9 yr) and age
      matched eight sedentary men (21.6+/-2.5 yr) participated in this study. Total
      body water and body water turnover were measured using the deuterium (D(2)O)
      dilution technique. Urine samples were obtained every day for 10 days after oral
      administration of D(2)O. The day-by-day concentrations were used to calculate the
      biological half-life of D(2)O and body water turnover. Maximal oxygen uptake
      (VO(2max)) and oxygen uptake corresponding to ventilatory threshold (VO(2VT)) as
      an index of aerobic capacity were determined during a graded exercise test. Both
      VO(2max) and VO(2VT) were higher in the exercise group than in the sedentary
      group (P<0.05). The biological half-life of D(2)O was significantly shorter in
      the exercise group than in the sedentary group (5.89+/-0.81 days vs. 7.52+/-0.77
      days, P<0.05), and the percentage of the body water turnover was significantly
      higher in the exercise group than in the sedentary group (11.99+/-1.96% vs.
      9.39+/-1.21%, P<0.05). The body water turnover was correlated with VO(2max) and
      VO(2VT), respectively (P<0.05). Based on these findings, this study speculates
      that a level of physical activity may induce a body water turnover higher in the
      healthy state, since the better trained subjects have a higher body water
      turnover.

PMID- 14646267
TI  - Oxidative stress, hogg1 expression and NF-kappaB activity in cells exposed to low
      level chromium.
AB  - Chromium compounds are carcinogenic to the human lung, although the detailed
      biochemical mechanism is still unclear. To understand the carcinogenic mechanism
      in cells exposed to low level hexavalent chromium, we measured the generation of
      reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine (8-OH-dG), the
      transcription of hogg1, which encodes an 8-OH-dG repair protein, and NF-kappaB
      activation levels in the A549 human lung epithelial cell line after exposure to
      Cr (VI) at concentrations of 12.5 to 800 microM. In A549 cells, ROS levels and
      DNA binding by NF-kappaB increased in proportion to the concentration of Cr (VI).
      These increases were diminished by pretreatment with catalase, superoxide
      dismutase, or D-mannitol, but the levels of 8-OH-dG and expression of hogg1 did
      not change significantly with Cr (VI) exposure. These results suggest that the
      induction of ROS and the activation of NF-kappaB are important in the
      carcinogenic mechanism of Cr (VI), but it is unlikely that Cr (VI) concentrations
      below 800 microM increase 8-OH-dG levels or the expression of hogg1.

PMID- 14646268
TI  - Enhancement of a sense of coherence and natural killer cell activity which
      occurred in subjects who improved their exercise habits through health education
      in the workplace.
AB  - We have previously demonstrated that a sense of coherence (SOC), a candidate for
      a mediating stress factor, is involved in natural killer cell activity (NKCA)
      reduced in smokers, whereas the relationship among exercise, NKCA and SOC is
      unclear. To clarify the effects of exercise on SOC and NKCA, we examined the
      changes in SOC and NKCA before and after health education to encourage exercise.
      Of one-hundred and one male office workers who received the health education for
      one year, 27 improved, 65 were unchanged and 9 had deteriorated exercise habits.
      The repeated measures analysis of variance showed that SOC in workers with
      improvement in the exercise habit were increased more significantly by the health
      education than those in workers without improvement (p<0.05). Although the change
      in NKCA produced by health education was recognized to be significantly different
      in those who had never smoked from that in current smokers (p<0.05), multiple
      regression analysis demonstrated that improvement in health practice
      significantly contributed to increases in both SOC (p<0.01) and NKCA (p<0.05) in
      never smokers, independently of other psychological factors. These results
      suggest that subjects with improvement in exercise enhance NKCA through increased
      SOC in never smokers.

PMID- 14646269
TI  - Leisure time physical activity as a determinant of self-perceived health and
      fitness in middle-aged male employees.
AB  - Self-perceived health and fitness are epidemiological predictors of subsequent
      mortality and/or functional limitation. The present study was designed to analyze
      which lifestyle factors contribute to good status of self-perceived health and
      fitness in middle-aged male employees. Participants (n=401) aged 50-59 were
      assessed as to the status of self-perceived health and fitness, and various
      lifestyle factors including nutrition, smoking, drinking, physical activity,
      psychological stress, sleeping and relaxation. Logistic regression analysis
      revealed that among the lifestyle factors surveyed in the present study, doing
      exercise/sports at a medium level (either > or =4.5METs/1-2 times per week or
      <4.5METs/> or =3-4 times per week) of physical activity index (PAI) was the only
      predictor of good self-perceived health. Similarly, doing exercise/sports at or
      above the medium level of PAI was identified as the only independent predictor of
      good self-perceived fitness. In addition, maintaining the habit of doing
      exercise/sports at or above the medium level of PAI throughout the year, and
      having this habit through the 4th and 5th decades of life or starting to have it
      from the age of 50 through 59 were important to obtain a good status of self
      perceived health and fitness. These findings suggest that leisure time physical
      activity level is a determinant of good health and fitness in the middle-aged
      male employees in the present study.

PMID- 14646270
TI  - Alcohol consumption, serum gamma-glutamyltransferase levels, and coronary risk
      factors in a middle-aged occupational population.
AB  - The relationships between alcohol consumption, serum gamma-glutamyltransferase
      (GGT) levels, and the prevalence of major coronary risk factors were analyzed
      cross-sectionally in 2,399 male and 1,402 female middle-aged workers, to clarify
      the effects of moderate alcohol consumption on the development of the metabolic
      syndrome. Male moderate drinkers, consuming less than 60 ml of alcohol per day,
      had a lower prevalence of upper body obesity and low serum HDL-cholesterolemia
      (LHDLC) in comparison with nondrinkers, but not of hypertension, impaired glucose
      tolerance or hypertriglyceridemia (HTG). In women, alcohol consumption did not
      show any significant associations with the coronary risk factors. Men with an
      elevated serum GGT (EGGT) of 40 U/l or above had a significantly higher odds
      ratio for all the coronary risk factors as compared with those with normal GGT,
      even after adjusting for alcohol consumption, together with age, body mass index,
      cigarette consumption and physical activity. Women with an EGGT of 25 U/l or
      above had similar findings, although significance was found only in HTG. Nearly
      80% and 55% of the appearance of EGGT in men and women were attributable to
      alcohol consumption, and 20% and 10% of the male and female moderate drinkers had
      EGGT. These results suggest that even moderate alcohol consumption will increase
      coronary risk factors characteristic of the metabolic syndrome in drinkers who
      have an increase in serum GGT. Further studies are required to confirm the causal
      association between alcohol consumption, increase in serum GGT and development of
      the metabolic syndrome.

PMID- 14646271
TI  - The relationship between cold exposure and hypertension.
AB  - This study was performed to determine whether there was any relationship between
      cold exposure and hypertension, and to evaluate risk factors affecting
      hypertension in cold-exposed workers. In 11 refrigeration industries, 68 male
      workers working in cold areas more than once per day were selected as the cold
      exposed group, and 68 workers not exposed to cold were selected as the control
      group. The questionnaire survey, clinical and laboratory tests were performed.
      Systolic and diastolic blood pressures were significantly higher in the cold
      exposed group, and body core temperature was significantly lower in the cold
      exposed group (p<0.05). In logistic regression analysis, age, cold exposure
      severity and milk intake were significant variables affecting hypertension in
      cold-exposed workers, whose odd ratios were 5.204 (95% CI 1.440-18.812), 2.674
      (95% CI 1.080-6.618), and 0.364 (95% CI 0.141-0.942), respectively. Cold exposure
      was a risk factor for hypertension, and risk factors affecting hypertension in
      cold exposed workers were age, cold exposure severity, and milk intake.
      Therefore, cold exposed workers should minimize cold exposure time as much as
      possible, and ingest foods containing calcium such as milk. In particular, old
      workers working in cold areas should check their blood pressure and
      electrocardiogram periodically.

PMID- 14646272
TI  - Gene expression of surfactant protein-A and thyroid transcription factor-1 in
      lungs of rats exposed to silicon-carbide whisker in vivo.
AB  - Intratracheal instillation studies have shown that exposure to silicon carbide
      whisker (SiCW), an asbestos substitute, produces pulmonary fibrotic changes,
      suggesting that SICW might have a fibrogenic potential. It is thought that
      surfactant protein is a good biomarker of lung injury and pulmonary fibrotic
      activity. In order to explore whether or not surfactant protein is associated
      with lung disorder through exposure to SiCW, we examined the expression of SP-A,
      SP-C and thyroid transcription factor-1 (TTF-1), a common transcription factor of
      SP-A and SP-C mRNA in lungs exposed to SiCW. Male Wistar rats were administered 2
      mg or 10 mg of SiCW suspended in saline by a single intratracheal instillation,
      and were sacrificed at 3 d, 1 wk, 1 month, 3 months and 6 months after the
      intratracheal instillation. RNA was subsequently extracted from the lungs, and
      expression of SP-A, SP-C and TTF-1 mRNA from the lungs was observed by reverse
      transcription-polymerase chain reaction (RT-PCR). Exposure to 2 mg of SiCW showed
      a decrease in mRNA of SP-A and TTF-1 at 6 months, but exposure to 10 mg of SiCW
      showed decreased levels of SP-A and TTF-1 mRNA at 3 d and 6 months. On the other
      hand, 2 mg of SiCW increased the level of SP-C mRNA from 3 d to 3 months, and 10
      mg of SiCW decreased the levels of SP-C mRNA in the rat lungs at 3 d, 1 month and
      6 months. No clear tendency to the expression of SP-C was observed, but the
      patterns of expression of TTF-1 and SP-A were similar. These data suggest that SP
      A and TTF-1 are associated with not only the acute phase but also the chronic
      phase in lungs exposed to SiCW.

PMID- 14646273
TI  - Interpersonal conflict, social support, and burnout among home care workers in
      Japan.
AB  - To examine associations between interpersonal relationships in work settings and
      burnout, a cross-sectional survey was conducted on home care workers in Sapporo,
      Japan, by using the Maslach Burnout Inventory (MBI) and scales of interpersonal
      conflict and social support developed by the authors. Questionnaires were
      distributed among 303 subjects and returned by 243 subjects (80%). Complete
      answers were obtained from 106 subjects and were used for analysis. In multiple
      regression analyses, conflict with clients and their families significantly
      related to emotional exhaustion and depersonalization of the MBI (p<.05).
      Supervisory conflict significantly related to emotional exhaustion (p<.05),
      whereas coworker conflict significantly associated with depersonalization
      (p<.01). It is suggested that conflicts with clients' families, as well as
      clients, are important indicators for emotional exhaustion and depersonalization
      of home care workers.

PMID- 14646274
TI  - Acute stroke mortality and air pollution: new evidence from Shanghai, China.

PMID- 14646275
TI  - Respiratory effects of chronic animal feed dust exposure.
AB  - AIM: The aim of our study was to assess the prevalence of chronic work related
      respiratory symptoms and to determine lung function abnormalities in animal feed
      industry workers. METHOD: 108 workers with a mean age of +/- SD: 32 +/- 7.11 yr
      employed in the animal feed industry and 108 unexposed subjects as a control
      group were enrolled in the study. All subjects filled out a questionnaire on
      their respiratory symptoms. Pulmonary function tests (PFTs) were conducted.
      Airborne dust (respirable fraction) was sampled during an 8-h work shift. Dust
      sampling was performed with a Casella AFC 123 machine. RESULTS: A significantly
      higher prevalence of work related upper and lower respiratory tract symptoms such
      as cough (12%), dyspnea (5.6%) and sinusitis (8.3%) were found among the workers
      than in the control group (p=0.001, p=0.04 and p=0.008 respectively). Irritation
      symptoms such as pruritus of the eyes (11.1%), skin lesions (7.4%) and nose
      symptoms (8.3%) were also significantly higher among workers that in the control
      group (p=0.001, p=0.014 and p=0.005 respectively). The mean PFTs (predicted %) of
      the workers; forced vital capacity (FVC)% +/- SD (85.23 +/- 12.06), 1-s forced
      expiratory volume (FEV1)% +/- SD (88.73 +/- 13.09), peak expiratory flow (PEF)%
      +/- SD (70.64 +/- 18.76) and forced expiratory flow rate at 25-75% of the FVC
      (FEF25-75)% +/- SD (88.42 +/- 25.94) were found significantly lower than in the
      control group (p<0.0001, p<0.0001, p<0.0001, p<0.0001 respectively). Our data
      indicate that exposure to animal feed dust is an important factor in the
      occurrence of respiratory symptoms and decline in lung functions.

PMID- 14646276
TI  - Estimation of trunk muscle parameters for a biomechanical model by age, height
      and weight.
AB  - To establish more accurate equations for estimating the moment arm length and
      cross-sectional area of the erector spinae and rectus abdominis muscles, the
      effects of height, weight and age on those muscles were analyzed by using a high
      order polynomial equation. Data on the moment arm length and cross-sectional area
      at L3/4 were obtained from MRI images of 152 males and 98 females. The
      statistical model used in this study has any combination of up to third-order
      independent variables for age, height and weight. The effective independent
      variables were selected by the forward step method of multiple regression
      analyses. The results of multiple regression analyses showed that the polynomial
      equations for the moment arm length of erector spinae in both genders, and that
      for the rectus abdominis in males, contained all three variables of age, height
      and weight. That for the moment arm length of female rectus abdominis contained
      the variables of weight and age. The multiple correlation coefficients of the
      erector spinae and rectus abdominis were 0.355 and 0.650 for males, 0.364 and
      0.411 for females, respectively. The equations for the cross-sectional area of
      the erector spinae in both genders, as well as that for male rectus abdominis
      contained only one variable (weight). The multiple correlation coefficients of
      the cross-sectional area of the erector spinae were 0.576 for males and 0.469 for
      females. The cross-sectional area of the female rectus abdominis had no effective
      variables.

PMID- 14646277
TI  - Effects of stress management program for teachers in Japan: a pilot study.
AB  - The aim of this study was to examine the effects of a stress management program
      for teachers on their stress responses, social support, and coping. Participants
      (n=24) were assigned to either an intervention or a waiting list control group. A
      five-session program, including psychoeducation, group discussion, role-playing
      and relaxation training, was conducted for the intervention group at two week
      intervals. Eight participants from each of the groups responded to pre- and post
      intervention questionnaire surveys. The positive intervention effect was
      significant for social support from co-workers (p=0.035), whereas the negative
      intervention effect was significant for proactive coping (p=0.033). No
      significant effect was observed for stress responses (vigor, anger, fatigue,
      anxiety, depression, and somatic stress responses) (p>0.05). The positive
      intervention effect was marginally significant for social support from co-workers
      (p=0.085) and anger (p=0.057) among those who at first had high stress response
      scores in the pre-intervention survey (n=5 and n=4 for the intervention and
      waiting list control groups, respectively). Furthermore, the positive
      intervention effect was significant for social support from co-workers (p=0.021)
      and marginally significant for resignation coping (p=0.070) among those who at
      first had high job control scores (n=4 and n=5 for the intervention and waiting
      list control groups, respectively). Results showed that the stress management
      program conducted in this study contributed to increasing social support from co
      workers. This study suggests that a program that focuses on a particular subgroup
      (e.g., those with high stress responses or high job control) might be effective
      in enhancing coping skills, increasing social support, and reducing stress
      responses.

PMID- 14646278
TI  - Critical dose of lead affecting delta-aminolevulinic acid levels.
AB  - To estimate the critical dose of the association between the blood lead
      concentration (BPb) and delta-aminolevulinic acid (ALA) levels, ALA levels in
      plasma (ALA-P), blood (ALA-B), and urine (ALA-U), and the activity of delta
      aminolevulinic acid dehydratase (ALAD) were determined in 186 Japanese lead
      workers, aged 18-62 yr, with BPb levels of 2.1-62.9 g/dl. For this purpose, the
      benchmark dose (BMD) method, recently used in the environmental health field in
      place of the no-observed-adverse-effect level, was introduced into this study.
      The BMD was defined as the BPb level that resulted in an increased probability of
      abnormal change in ALA-related parameters by an excess risk (BMR) of 5% in
      exposed workers i.e., from P0 (abnormal probability of 5% in unexposed workers)
      to P0+BMR for exposed workers at the BMD. ALA-related parameters were
      significantly correlated with BPb. The BMDs computed from the 186 workers, after
      controlling for age, were 15.3-20.9 microg/dl for ALA levels, and 2.9 microg/dl
      for ALAD; likewise, the BMDs from the 154 workers with BPb levels of less than 40
      microg/dl were 3.3-8.8 microg/dl for ALA levels, and 2.7 microg/dl for ALAD.
      Since the cutoff value of ALA-P, computed from the latter workers, seems to be
      closer to the upper normal limit in unexposed adults than does that from the
      former workers, it is suggested that the critical dose of BPb causing the
      increased levels of ALA is below 10 microg/dl. Such critical doses are necessary
      to promote preventive activities of adverse effects of lead.

PMID- 14646279
TI  - Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary
      study.
AB  - Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of
      carbon monoxide from automobiles emissions. Therefore, addition of ETOH in
      reformulated fuel will most likely increase and the involuntarily human exposure
      to this chemical will also increase. This preliminary study was undertaken to
      evaluate the possible neuromotor effects resulting from acute ETOH exposure by
      inhalation in humans. Five healthy non-smoking adult males, with no history of
      alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment
      exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in
      air) for six hours. Reaction time, body sway, hand tremor and rapid alternating
      movements were measured before and after each exposure session by using the
      CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood
      and in alveolar air were also measured. ETOH was not detected in blood nor in
      alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of
      exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml
      and 253.1 ppm, respectively. The neuromotor tests did not show conclusively
      significant differences between the exposed and non-exposed conditions. In
      conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or
      lower or to concentrations that could be encountered upon refueling is not likely
      to cause any significant neuromotor alterations in healthy males.

PMID- 14646280
TI  - Systemic effects of orally administered p, p'-DDE on immature male Wistar rats
      during pubertal period.
AB  - Systemic effects of p, p'-DDE (1, 1-dichloro-2, 2 bis (p-chlorophenyl) ethylene;
      DDE) on immature male rats were investigated in pubertal Wistar rats after oral
      administration of DDE. Special rat chow containing 125 ppm DDE (approximately 10
      mg/kg DDE) had been administered daily for 42 d since 6 wk of age and its effects
      had been observed until 12 wk of age. The administration of DDE did not produce
      any overt signs of toxicity. Neither physical development nor sexual maturation
      was affected, and serum biochemistry was not impaired at the dose used in this
      experiment. Moreover, the male reproductive organs and epididymal sperm count
      were not affected by the administration of DDE during the pubertal period. Our
      results showed that even immature male rats were resistant to DDE exposure at the
      daily dose of ca. 10 mg/kg, but metabolic and immunological changes still
      remained uncertain. Further investigation should be conducted to reveal all the
      effects of DDE on immature male rats.

PMID- 14646281
TI  - Biological monitoring of indium by means of graphite furnace atomic absorption
      spectrophotometry in workers exposed to particles of indium compounds.

PMID- 14646282
TI  - Associations of sense of coherence with sickness absence and reported symptoms of
      illness in Japanese civil servants.

PMID- 14646283
TI  - A mental health care program and sickness absence in a Japanese manufacturing
      plant.

PMID- 14646284
TI  - Environmental mycological study and respiratory disease investigation in fur
      processing workers.
AB  - This paper presents the results of an investigation of respiratory symptoms,
      chest X-ray examinations, and analysis of antibodies to fungi of 138 fur
      processing workers and 40 control workers. Industrial hygiene survey and
      environmental mycological studies were also conducted. The dust concentrations in
      fur processing workshops (1.8-6.7 mg/m3) were below the national health limit (10
      mg/m3). Most dusts in all fur processing workshops contained less than 2.0%
      silica. Numbers of isolated fungi in fur processing workshops [629-3,681 cfu/m3
      (colony forming unit/m3)] were significantly higher than those in control
      environments (63-503 cfu/m3). The prevalences of respiratory symptoms in fur
      processing workers were higher than those in control workers, especially among
      female exposed workers. The prevalences of the symptoms in female exposed workers
      were 37.9% with chronic cough, 28.4% with chronic phlegm, 10.5% with dyspnea,
      22.1% with chest tightness, and 4.2% with fever. Seven cases showed abnormalities
      in chest X-ray examinations. The OD450nm values for antibodies to fungi in fur
      processing workers were significantly higher than those in control workers
      (P<0.05). The prevalences of positive anti-fungi antibodies in fur-processing
      workers were also significantly higher than those in control workers (p<0.01).
      The results suggested that fungi might be one of the main allergens in
      respiratory diseases in fur processing workers.

PMID- 14646285
TI  - Plasma concentration of adrenocorticotropic hormone in traffic policemen.
AB  - The aim of this study is to evaluate whether traffic policemen exposed to urban
      pollutants and possible psycho-social stressors could be at risk of changes on
      plasma adrenocorticotropic hormone [ACTH(P)] levels compared to a control group.
      Traffic policemen were matched by sex, age, length of service and drinking habit
      (<50 g of wine or beer per day) with a control group after excluding principal
      confounding factors; 62 traffic policemen with outdoor activity (34 men and 28
      women) and 62 control subjects with indoor activity (34 men and 28 women) were
      included in the study. The levels of ACTH(P) were significantly higher in male
      and female traffic policemen than in the control subjects (respectively P=0.040,
      P=0.043). The authors hypothesise that occupational exposure to chemical and
      physical stressors, that may interact with possible psycho-social stressors,
      could cause a change in ACTH(P) levels in traffic policemen.

PMID- 14646286
TI  - A proposal for topic-based impact factors and their application to occupational
      health literature.

PMID- 14646287
TI  - Interstitial pneumonia developed in a worker dealing with particles containing
      indium-tin oxide.

PMID- 14646288
TI  - Assessment of urinary cotinine as a marker of nicotine absorption from tobacco
      leaves: a study on tobacco farmers in Malaysia.
AB  - To assess dermal absorption of nicotine from tobacco leaves in relation to Green
      Tobacco Sickness (GTS), urinary cotinine concentrations were measured in 80 male
      tobacco-growing farmers and in 40 healthy males (controls) who did not handle wet
      tobacco leaves in Kelantan, Malaysia. Among non-smokers, urinary cotinine levels
      in farmers were significantly higher than those of controls; farmers with urinary
      cotinine of 50 ng/ml/m2 or above showed eye symptoms more frequently than those
      below this level (p<0.05). Farmers who did not wear protective equipment had
      subjective symptoms more frequently than those who used the equipment (p<0.05);
      some of these symptoms were seen more frequently in organophosphate (Tamaron)
      users than in non-users. As tobacco farmers evidence a risk of nicotine poisoning
      from tobacco leaves, assessment including GTS together with effects of pesticides
      will be necessary.

PMID- 14646289
TI  - Effect of acute exposure to loud occupational noise during daytime on the
      nocturnal sleep architecture, heart rate, and cortisol secretion in healthy
      volunteers.
AB  - OBJECTIVES: Noise is one of the commonest physical stressors to which industrial
      workers are exposed. Many workers complain of symptoms associated with a non
      specific generalized stress response, including disturbed sleep. However,
      industrial workers may be exposed to more than one source of stress and it is not
      possible to completely attribute the disturbed nocturnal sleep and changes in
      heart rate to the effects of loud noise alone. This study was done to find out
      whether acute exposure of healthy individuals to loud occupational noise during
      the daytime would cause changes in their nocturnal sleep architecture, heart rate
      during sleep and serum cortisol levels. METHODS: Baseline polysomnography was
      done on ten subjects who were exposed for eight hours either to continuous
      occupational background noise levels of >75dB(A), or a quiet environment. Sleep
      polysomnography was done on the night prior to and after exposure. Blood was
      collected for serum cortisol estimation at night prior to sleep and in the
      morning after waking up. Statistical analysis was done by repeated measures ANOVA
      with Tukey's post test. RESULTS: The sleep efficiency was less than 80% and the
      total time spent in Rapid Eye Movement (REM) sleep, Slow Wave Sleep (SWS) and the
      REM onset latency were significantly decreased on the night after exposure to
      noise. There was a significant increase in stage shifts. The percentage fall in
      heart rate during sleep was decreased compared to the baseline values. The serum
      cortisol levels in the morning after exposure to noise was significantly
      increased. CONCLUSION: Workers exposed to loud background occupational noise
      react to the stress and show changes in nocturnal sleep architecture and heart
      rate which may be contributed to the exposure to noise.

PMID- 14646290
TI  - Evaluating the efficacy of a thermal exposure chamber designed for assessing
      workers' thermal hazard.
AB  - This study was conducted on a thermal exposure chamber designed for assessing
      workers' thermal hazard. In order to assess the efficacy of the studied chamber,
      three environmental conditions were selected to simulate high, middle and low
      thermal impact situations, with air temperatures (Ta) of 43.12, 36.23 and 25.77
      masculine C, globe temperatures (Tg) of 44.41, 41.07 and 29.24 masculine C,
      relative humidity (RH) of 77, 59 and 39%, and air flow velocities (Va) of 1.70,
      0.91 and 0.25 m/s, respectively. For the three specified thermal impact
      conditions, results show that the coefficients of variation (CVs) for Ta, Tg, RH
      and Va measured in the chamber studied were consistently less than 10%, except
      for Va under the low thermal impact condition (=50%). For each specified thermal
      impact condition, we generated 1,000 environmental combinations by using the
      Monte Carlo simulation approach according to the variations obtained from the
      four environmental factors. We directly adopted the ISO 7933 approach to estimate
      the allowable exposure time (AET) for each simulated environmental condition.
      This study yielded a range in the 95% confidence interval (95% CI) of the
      estimated AETs for the three specified thermal impact conditions which were
      consistently less than 5 min. We further conducted the sensitivity analysis to
      examine the effect of the four environmental factors on estimating AETs. We found
      Va was the least important factor in estimating AETs for any specified thermal
      impact condition. In conclusion, although Va was found with great variation for
      the chamber specified in the low thermal impact condition, the exposure chamber
      studied can still be regarded as a feasible one for assessing workers' thermal
      hazard.

PMID- 14646291
TI  - Effects of genetic polymorphisms in metabolic enzymes on the relationships
      between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1
      hydroxypyrene and 2-naphthol concentrations.
AB  - This study was designed to investigate the relationship between environmental
      exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to
      evaluate the effects of cigarette smoking and the genetic polymorphisms of
      CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this
      study were 105 healthy Korean males without occupational exposure to PAHs. The 8
      hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene
      (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid
      chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6
      were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a
      significant correlation with the 1-OHP concentration in all subjects (p<.001) and
      in smokers (p<.01), and with the 2-naphthol level in non-smokers (p<.01). The 8
      OHdG level was significantly higher in smoking rapid acetylators than in smoking
      slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type
      than in those with the UGT1A6 mutant genotype. Significant positive correlations
      between 8-OHdG and 1-OHP concentrations were found in subjects with every
      genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2
      genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The
      urinary 2-naphthol level significantly correlated with the 8-OHdG level only in
      subjects with the GSTM1 null-type. In conclusion, there is a significant
      correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP
      concentration in the population not occupationally exposed to PAHs. This
      relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

PMID- 14646292
TI  - Urinary PAH metabolites influenced by genetic polymorphisms of GSTM1 in male
      hospital incinerator workers.
AB  - Hospital waste incinerator workers are exposed to various pyrolysis products
      including polycyclic aromatic hydrocarbons (PAHs). We evaluated their exposure by
      assessing urinary 1-hydroxypyrene glucuronide (1-OHPG), as an internal dose of
      PAH exposure. The potential effect of genetic polymorphisms of GSTM1/T1 involved
      in PAH metabolisms was also investigated. Pre- and post-shift samples were
      collected from 28 hospital incinerator workers. Urinary 1-OHPG was assayed by
      synchronous fluorescence spectroscopy (SFS) after immunoaffinity purification
      with the monoclonal antibody 8E11. Genotypes of GSTM1/T1 were assessed by PCR
      based methods. Information on smoking habits and use of personal protective
      equipment were collected by means of a self-administered questionnaire. The Mann
      Whitney test was used to compare group means of these biomarkers. Urinary 1-OHPG
      levels were similar in pre- and post-shift urine samples. The arithmetic mean
      concentrations of urinary 1-OHPG were 0.16 +/- 0.04 micromol/mol creatinine pre
      shift and 0.19 +/- 0.09 micromol/mol creatinine post-shift, but urinary 1-OHPG
      levels were significantly higher in individuals with the GSTM1 null genotype than
      with the GSTM1 present genotype (p=0.05, by Mann-Whitney test). Our results
      suggest that the urinary 1-OHPG levels in hospital waste incinerator workers may
      be modified by the GSTM1 genotype, but these findings remain to be confirmed in
      future studies involving larger sample sizes.

PMID- 14646293
TI  - Study on incidence of needle stick injury and factors associated with this
      problem among medical students.
AB  - Medical students face the threat of needle stick injury with the consequent risk
      of acquiring blood-borne infection by pathogens such as HIV, Hepatitis B and
      Hepatitis C while performing their clinical activities in the hospitals. A cross
      sectional study was conducted among 417 final year medical students from
      Universiti Kebangsaan Malaysia (UKM), University Malaya (UM) and Universiti Putra
      Malaysia (UPM). The aims of the study were to determine the incidence of cases
      and episodes of needle stick injury among them in the past year. This study was
      also done to find out the factors that might be associated with the occurrence of
      this problem. The factors were sociodemographic factors, duration of exposure,
      level of knowledge of blood-borne diseases and Universal Precaution, perception
      of risk of blood-borne diseases and level of practice of Universal Precaution.
      The incidence of needle stick injury among medical students was 14.1% (59 cases).
      The total number of episodes of needle stick injury was 87 and the incidence of
      episodes among respondents was high i.e. 20.9%. The highest incidence of episodes
      of needle stick injury occurred in Obstetric & Gynaecology postings, followed by
      Medicine and Surgery. For clinical procedures, venepuncture had the highest
      incidence followed by setting up drips and giving parenteral injections. The
      results showed the students who had needle stick injury (cases) had lower scores
      in the practice of Universal Precautions than non-cases (p<0.05). There was a
      significant association between the level of practice of Universal Precautions
      and the number of episodes of needle stick injury, i.e. the higher the score for
      the practice of Universal Precautions, the lower the number of episodes (beta=
      2.03 x 10(-2), p<0.05). This study showed that medical students are at risk of
      needle stick injury and blood-borne infections during their clinical activities
      while performing procedures on patients especially for those who were poor at
      practising Universal Precautions. Therefore some preventive measures should be
      taken by the management of the universities and medical students to avoid the
      occurrence of these problems.

PMID- 14646294
TI  - Influence of gender, age and lifestyle factors on micronuclei frequency in
      healthy Japanese populations.

PMID- 14646295
TI  - Cavitating BOOP associated with myeloperoxidase deficiency in a floor cleaner
      with an incidental heavy exposure to benzalkonium compounds.

PMID- 14646296
TI  - Relationship between burnout and communication skill training among Japanese
      hospital nurses: a pilot study.
AB  - We investigated the relationship between burnout and communication skill training
      among Japanese hospital nurses to improve the mental health of human service
      workers. The subjects were forty-five registered nurses referred to a self
      expression skill intervention program by their section superiors, with each
      superior choosing from two to five nurses. The hospital was located in the Kyushu
      area and staffed by about four hundred nurses. The subjects were divided into an
      intervention group (19 nurses) and a reference group (26 nurses). The
      intervention group received the communication skill training in July and August,
      2001. The communication skill training was carried out in accordance with the
      assertiveness training (AsT) precepts of Anne Dickson. In June, 2001, we
      delivered a set of questionnaires including age, gender, working years, a burnout
      scale, and a communication skill check-list as a baseline survey. The baseline
      questionnaires were returned at the end of June, 2001. In January, 2002, we
      delivered the same questionnaire again to the two groups and collected them at
      the end of the month. Excluding the only male and insufficient answers, twenty
      six nurses (58%) returned complete answers in the initial and subsequent surveys.
      We found that the personal accomplishment and the two communication skills such
      as "accepting valid criticisms" and "negotiation" of the intervention group had
      improved significantly five months after the training as compared with that of
      the reference. Our results implied that communication skill training might have a
      favorable effect on burnout among Japanese hospital nurses.

PMID- 14646297
TI  - A study of childhood poisoning at National Poisons Information Centre, All India
      Institute of Medical Sciences, New Delhi.
AB  - A retrospective analysis of the poisoning calls received by the National Poisons
      Information Centre (NPIC) showed a total of 2,720 calls during a period of three
      years (April 1999-March 2002). Poisoning in children was reported in 995 calls
      (36.6%). The age ranged from less than 1 yr to 18 yr and the age groups involved
      were divided into four categories (0-6 yr, >6-12 yr, >12-16 yr, >16-18 yr). The
      most vulnerable age group included children from less than one year to 6 yr old.
      Males outnumbered females (M=628, F=367). Although the accidental mode was the
      commonest (79.7%), intentional attempts were also noticed (20.2%) in the >12-16
      yr and >16-18 yr age groups. In the majority of cases, the route was oral (96.8%)
      followed by dermal exposure (3.2%) comprising bites and stings. Various types of
      agents belonged to classes of household products (47.0%), drugs (21.8%),
      industrial chemicals (7.9%), agricultural pesticides (9.1%), bites and stings
      (3.2%), plants (1.5%), miscellaneous products (5.3%) and unknown products (4.0%).
      The incidence of poisoning was highest due to household products comprising
      mainly pyrethroids, parad/thermometer mercury, rodenticides, phenyl, detergents
      and corrosives, etc. Poisoning due to drugs mainly included anticonvulsants,
      thyroid hormones, benzodiazepines, analgesics and oral contraceptives. Among the
      agricultural pesticides aluminium phosphide was the most commonly consumed,
      followed by organochlorines and organophosphates, etc. Paint thinners were common
      among industrial chemicals. Bites and stings were mainly snake bites and scorpion
      stings. Poisoning due to plants was low and Datura was commonly ingested.
      Although these data may not give an exact picture of the incidence rate in our
      country, due to underreporting of calls to the Centre and because the actual
      incidence might be higher or even variable, but they do give the trend in India,
      indicating that a strong emphasis should be placed on a prevention campaign which
      can at least reduce the occurrence of accidental pediatric poisoning.

PMID- 14646298
TI  - Neuropsychiatric effects in workers with occupational exposure to carbon
      disulfide.
AB  - In a cross-sectional study, prevalence of dysfunctions of the central nervous
      system was assessed in 134 male workers exposed to different levels of carbon
      disulfide (CS2) in a rayon viscose plant and compared to 38 non-exposed workers.
      In three groups of workers from the same plant with different levels of CS2
      (heavy, intermediate, none) estimated by personal samplers, disorders in the
      central nervous system were examined by means of psychiatric examination and
      questionnaire 16 (Q16). Unconditional logistic regression was calculated adjusted
      for age, alcohol consumption and education. Psychoorganic syndrome was diagnosed
      significantly more often in workers with heavy CS2 exposure, with adjusted OR of
      17.9 (95% CI 2.18-146.73), and insignificantly in workers with intermediate
      exposure. Prevalence of workers with more than 6 positive answers on the Q16 was
      higher in the heavily exposed workers (OR=4.76; 95% CI 1.80-12.60). A similar
      result was found for almost all the questions in the Q16, and the most pronounced
      psychological symptom was of less interest in sex (adjusted OR=8.14; 95% CI 2.19
      30.22). High correlation was found between symptoms recorded on neuropsychiatric
      examination and on Q16. Both neuropsychiatric exams and Q16 indicated
      disturbances in the central nervous system due to the long-term heavy exposure to
      CS2. Disorders of the central nervous system were found more often in workers
      with heavy exposure to CS2. Questionnaire Q16 is a valuable means for selecting
      workers for further neuropsychiatric testing.

PMID- 14646299
TI  - Spirometric measurements among quartz stone ex-workers of Gujarat, India.
AB  - The present cross sectional study was carried out among 134 ex-workers from
      quartz stone crushing units. Using the interview technique as a tool for data
      collection, demographic and occupational details of the subjects were recorded on
      the predesigned proforma. Standard diagnostic criteria were used for diagnosing
      silicosis and silico-tuberculosis. The pulmonary functions of the subjects were
      measured with Spirovit SP-10. The mean age of the males was found to be 33.18 +/-
      10.39 yr and that of the females was 30.10 +/- 9.3 yr and for the whole group was
      31.77 +/- 9.99 yr. Mean duration of exposure was 2.74 +/- 1.65 yr. The study
      variables included age, sex, duration of exposure, smoking and respiratory
      morbidity. Forced Vital Capacity (FVC) which suggests lung parenchymal disorders
      was found to be significantly reduced with female sex, presence of smoking,
      increasing duration of exposure and presence of pneumoconiosis, whereas the lung
      function parameters indicating the status of airways were found to be
      significantly reduced with all the factors. Therefore, it was concluded that
      quartz stone workers exposed to approximately 100% free silica had deteriorated
      lung function which can be attributed mainly to respiratory disorders along with
      other epidemiological factors such as age, sex, duration of exposure and smoking.

PMID- 14646300
TI  - Determining of crystalline silica in respirable dust samples by infrared
      spectrophotometry in the presence of interferences.
AB  - Infrared Spectrophotometry (IR) is now widely used to determine crystalline
      silica in industrial dust samples. Though the IR method has many advantages when
      dealing with respirable dust samples, some serious analytical errors are often
      caused by interference minerals contamination. These minerals have a
      characteristic absorption band corresponding in position to the analytical peak
      for crystalline silica. In this paper, six typical interference minerals
      (Kaolinite, Mullite, Muscovite, Pyrophyllite, Montmorillonite and Amorphous
      silica) were pre-size controlled to respirable range and their infrared spectra
      were measured by means of an FT-IR with the well-known potassium bromide tablet
      technique. The effects of these interference minerals on the Japanese OEL or the
      administrative control level for respirable dust which depend on the silica
      content were calculated and expressed in figures. The measured absorption
      coefficients of the interference minerals and quartz were 1.36-6.98 Abs/mg and
      24.46 Abs/mg, respectively. The absorption band height ratios of each
      interference minerals were also measured. Then the efficiency and applicability
      of two spectrum correction methods for the interference minerals, absorbance
      ratio method and difference spectrum method were examined by using artificially
      mixed samples (standard interference mineral + standard quartz). By comparing the
      quantifying results for the mixture samples, it was revealed that the interfered
      spectra were almost corrected successfully when using the difference spectrum
      method, whereas correction by the absorbance ratio method resulted in apparent
      negative errors. Furthermore, the difference spectrum method was proven to be
      superior to the absorbance ratio method in applicability.

PMID- 14646301
TI  - Assessment of exposure to magnetic fields in occupational settings.
AB  - OBJECTIVE: It is important to have data about occupational magnetic field
      intensity to consider the contribution of occupational magnetic field exposure on
      the human body. We conducted research on exposure to occupational magnetic fields
      and tried to qualify data on the distribution of magnetic field' intensity in
      certain general working environments with individual measurements. SUBJECTS AND
      METHODS: We performed sample research on the exposure to low-frequency magnetic
      fields of workers in certain occupations and in the working environment. We also
      assessed the relationship between working environmental magnetic field
      distribution and individual exposure. RESULTS: Some occupations were found to be
      exposed to high magnetic fields. We observed that some workspaces, such as the
      transformer substation, generally had a uniform and high magnetic field
      measurement but employees were exposed to a lower intensity. We also found that
      welders were exposed to high magnetic fields at about 600 microT in a very short
      time but with a geometrical value of 0.08 microT. CONCLUSION: The determination
      of administrative levels and control levels, not only of the time weighted
      average of threshold limits or short term exposure limits, but also ceiling
      limits should be considered. More systematic research is necessary to determine
      variables such as operating conditions, measuring position, and frequency bands.
      Also, further studies will be needed to make a job-exposure matrix for the
      magnetic fields for each occupation type and to combine it with exposure in non
      occupational settings such as commuting and ordinary life situations to explore
      the causal relationship between exposure to magnetic fields and disease.

PMID- 14646302
TI  - Lack of relationship between occupational exposure to carbon disulfide and
      endocrine dysfunction: a six-year cohort study of the Japanese rayon workers.
AB  - OBJECTIVES: A six-year prospective cohort study was conducted to clarify whether
      the current carbon disulfide (CS2) exposure level is low enough to prevent
      subclinical health impairment and/or to ameliorate health effects due to previous
      high exposure. This paper describes the follow-up results, exposure assessment,
      and effects on the endocrine system. METHODS: The study subjects were 432 male
      workers exposed to CS2 at one of the 11 rayon factories in Japan and 402 referent
      workers from the same factories, all of whom were examined in 1992-93. 251 CS2
      exposed, 140 former-exposed and 359 referent workers participated in the follow
      up survey (follow-up rate 89.9%) in 1998-99. Urinary 2-thiothiazolidine-4
      carboxylic acid (TTCA) at the end of a shift as internal exposure index and the
      time-weighted average CS2 concentration as external exposure index were measured
      twice a year from 1992-1993. By using various blood indices, we evaluated effects
      on thyroid, hypophysis, and gonad function, as well as effects on glucose
      metabolism. Information on potential confounding factors, such as age, smoking
      and alcohol drinking, were collected and adjusted for. RESULTS: When the
      individual exposure level was represented by arithmetic mean for TTCA and CS2
      concentration, geometric means (SD) of CS2 workers were 1.61 (1.91) mg/g.crea and
      5.02 (1.84) ppm, respectively. There were no exposure-related differences in
      glucose metabolism or any of the endocrinological indices. CONCLUSIONS: No
      biologically significant effects of CS2 were found on endocrine function in
      Japanese rayon manufacturing workers when the average internal and external
      exposure levels were maintained below the current occupational exposure limit.

PMID- 14646303
TI  - A case-crossover analysis of air pollution and daily mortality in Shanghai.
AB  - We used a case-crossover approach to assess the association between air pollution
      and daily mortality in Shanghai from June 2000 to December 2001. By design, this
      method can avoid some common concerns about the time-series approach, which was
      most frequently used to assess the short-term effects of air pollution. Different
      control periods (unidirectional and bi-directional control samplings) were used
      for the analysis. With a bi-directional six control sampling approach, the
      results from a conditional logistic regression model controlling for weather
      conditions showed that each 10 microg/m3 increase over a 48-h moving average of
      PM10, SO2 and NO2 corresponds to 1.003 (95%CI 1.001-1.005), 1.016 (95%CI 1.011
      1.021), and 1.020 (95%CI 1.012-1.027) relative risk of non-accident mortality,
      respectively. The association between air pollution and mortality for chronic
      obstructive pulmonary diseases (COPD) and cardiovascular causes was found to be
      closer than that for all causes. The results confirmed the deleterious role of
      the current air pollution level on human health in Shanghai, and provided
      information on the applicability of case-crossover design in studying the acute
      health effects of air pollution.

PMID- 14646304
TI  - Development of a light sensing self-adjusting hood for welding fumes.

PMID- 14646305
TI  - Fatal occupational injuries in Yugoslavia: 1990 to 1999.

PMID- 14646306
TI  - Adverse health experience in male workers during the boom economy in Japan.

PMID- 14646307
TI  - Adverse environmental health effects of ultra-low relative humidity indoor air.
AB  - In Japan, relative humidity (RH) shows the lowest achievement rate among the
      various general air quality standards for work environment. It has been mainly
      contributed by airtight design of modern buildings and occurrence of dry outdoor
      air in winter. Furthermore, an ultra-dry air environment of nearly 0% RH is often
      required in sophisticated industries. In order to assess the adverse health
      effects of the ultra-dry air environment, using a self-reported questionnaire, we
      have undertaken a study of over 200 employees of a high-tech device developing
      laboratory having a room at 2.5% RH (ultra-dry room). Those who worked in the
      ultra-dry room were identified and the prevalence of symptoms was compared with
      the other workers. Analysis was performed by Wilcoxon's test and Fisher's exact
      test. In the ultra-dry room, all the twelve workers covered their skin with long
      sleeve clothes, paper caps, paper masks and latex gloves. They reported skin
      symptoms more often (p<0.05) than the other workers (N=143). The prevalence of
      atopic dermatitis was also higher in the exposed workers (p<0.05). The complaints
      of workers in the ultra-dry environment were similar to preceding reports
      concerning moderately dry environmental exposures. The current precautions to
      protect the workers from the adverse effects of ultra-low RH appear to be
      insufficient, indicating that additional measures such as selection of
      appropriate clothing to mere skin coverage should be considered.

PMID- 14646309
TI  - In situ observation of the four-step dehydration process of the 1 beta
      methylcarbapenem antibiotic CS-834 crystal by X-rays.
AB  - The 1 beta-methylcarbapenem antibiotic CS-834 takes six crystalline forms
      depending on ambient conditions. The X-ray powder diffraction revealed that the
      dihydrate crystal (B2-form) was changed to the monohydrate (B1-form) through the
      intermediate form (B2'-form). The monohydrate form was then changed to the
      dehydrate (B0-form) through the intermediate B1'-form. The progress of the
      dehydration along the needle axis (c-axis) was observed under a microscope. When
      a single crystal of the B2-form was mounted on a diffractometer and the humidity
      was reduced, the crystal was gradually changed to the various dehydration forms
      with retention of the single crystal. The crystals of B2- to B0-forms form
      isostructures to each other except the solvent water molecules. In the crystal
      structure of the B1-form, the pivaloyloxymethyl moiety is disordered. One is
      nearly similar to that of the B2-form, while another is similar to that of the B0
      form. Each crystal structure consists of a columnar arrangement of CS-834 along
      the c-axis, and the water molecules are located between the columns and form a
      characteristic hydrogen bond network. When the water molecules leave the crystal,
      the columns slide slightly following the slight conformational change in the
      pivaloyloxymethyl groups and are connected by another type of hydrogen bond
      network. Such a rearrangement of the hydrogen bond network should be a motive
      force of the phase change to the next step due to the dehydration. Since the
      hydrogen bond network extends along the c-axis, the dehydration proceeds along
      the c-axis as observed microscopically.

PMID- 14646308
TI  - Antiedematogenic activity of two thiazolidine derivatives: N-tryptophyl-5-(3,5-di
      tert-butyl-4-hydroxybenzylidene) rhodanine (GS26) and N-tryptophyl-5-(3,5-di-tert
      butyl-4-hydroxybenzylidene)-2,4-thiazolidinedione (GS28).
AB  - The search for new anti-inflammatory drugs has been constant in several research
      centers. The use of the Bioisostery concept allows the elaboration of new
      bioactive compounds with different properties through the introduction of
      substitute groups in one or more positions of a main molecule with known
      biological activity. Preliminary works accomplished at our laboratory with 2,4
      thiazolidinedione isosters demonstrated inhibitory activity on edema formation
      for N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2,4-thiazolidinedione
      (GS28) and N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene) rhodanine
      (GS26). We verified the antiedematogenic and ulcerogenic activity of these two
      compounds in Wistar rats. The carrageenan induced paw edema suffered significant
      (p<0.05) inhibition (28.36% on average) for GS28 (100 mg/kg; v.o.) during the
      entire time of the experiment. GS26 (50 and 100 mg/kg; v.o.) significantly
      inhibited (p<0.05) the paw edema dextran induced (22.1 and 27.8%, for the
      respective doses) after 180 min. The compounds GS26 and GS28 did not show
      ulcerogenic activity on gastric mucous. The results suggest antiedematogenic
      action for both compounds without the appearance of gastric lesions.

PMID- 14646310
TI  - Preparation of optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid
      (threo-beta-phenylserine) via optical resolution.
AB  - To obtain optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (1),
      (2RS,3SR)-2-benzoylamino-3-hydroxy-3-phenylpropanoic acid [(2RS,3SR)-2] was first
      optically resolved using (1S,2S)- and (1R,2R)-2-amino-1-(4-nitrophenyl)-1,3
      propanediol as the resolving agents to afford (2R,3S)- and (2S,3R)-2 in yields of
      73% and 66%, based on half of the starting amount of (2RS,3SR)-2. Next, the
      racemic structures of ammonium and some organic ammonium salts of (2RS,3SR)-2
      were examined based on melting point, solubility, and infrared spectrum, with the
      aim of optical resolution by preferential crystallization. The benzylammonium
      salt of (2RS,3SR)-2 was suggested to exist as a conglomerate at room temperature,
      although it forms a racemic compound at the melting point. The optical resolution
      by preferential crystallization of the racemic salt afforded the (2R,3S)- and
      (2S,3R)-salts with optical purities of 90-97%. The (2R,3S)- and (2S,3R)-2
      obtained from the purified salts were hydrolyzed by reflux in hydrochloric acid
      to give (2R,3S)- and (2S,3R)-1.

PMID- 14646311
TI  - A synthesis of chiral 1,1,3-trisubstituted 1,2,3,4-tetrahydro-beta-carbolines by
      the Pictet-Spengler reaction of tryptophan and ketones: conversion of (1R,3S)
      diastereomers into their (1S,3S)-counterparts by scission of the C(1)-N(2) bond.
AB  - The Pictet-Spengler cyclization of the imines (3) prepared by the condensation of
      L-tryptophan methyl ester (1) and aryl methyl ketones (2), using titanium(IV)
      isopropoxide as an iminating reagent, quantitatively proceeded, when treated with
      trifluoroacetic acid (TFA) or formic acid, to provide two diastereomers, that is
      (1S,3S)-1-aryl-3-isopropoxycarbonyl-1-methyl-1,2,3,4-tetrahydro-beta-carbolines
      (4) and their (1R,3S)-diastereomers (5), of which the diastereomer ratios varied
      from 1 to 5 depending on the reaction conditions. The (1R,3S)-diastereomers (5)
      are thermodynamically more stable than their (1S,3S)-congeners (4), as shown by
      equilibration experiments in TFA. The conversion of 4 to 5 (also 5 to 4) should
      occur under acidic conditions by cleavage of the C(1)-N(2) bond with complete
      retention of configuration at the C-3 chiral center. The low diastereo
      selectivity observed in the Pictet-Spengler reaction of 1 and 2 is concluded to
      be a stereochemical outcome under conditions of kinetic control (lower
      temperature, shorter reaction time), while the high diastereo selectivity with
      preferential formation of the more stable isomer (5) is the result of
      thermodynamically controlled experiments (higher temperature, longer reaction
      time).

PMID- 14646312
TI  - Flavonoids from Andrographis viscosula.
AB  - Phytochemical investigation of the whole plant of Andrographis viscosula has led
      to the isolation of three new 2'-oxygenated flavonoids, (2R)-5-hydroxy-7,2',3'
      trimethoxyflavanone (1), 7,2',5'-trimethoxyflavone (2), 5,7,2',3'
      tetramethoxyflavone (3), and eight known flavones, 5,7,2'-trimethoxyflavone (4),
      5,7,2',4',5'-pentamethoxyflavone (5), echioidinin (6), 5,2',6'-trihydroxy-7
      methoxyflavone (7), 5-hydroxy-7,2'-dimethoxyflavone (8), echioidin (9),
      echioidinin 5-O-glucoside (10), and 5,2',6'-trihydroxy-7-methoxyflavone 2'-O
      glucoside (11). The structures of 1-11 were elucidated by physical and spectral
      methods, including extensive 2D NMR studies. The presence of 2'-oxygenated
      flavonoids is apparently restricted to Andrographis species in Acanthaceae.
      Therefore, 2'-oxygenated flavonoids are regarded as chemotaxonomic markers of
      Andrographis genus in the Acanthaceae family.

PMID- 14646313
TI  - Structures of 1,4-benzodioxane derivatives from the seeds of Phytolacca americana
      and their neuritogenic activity in primary cultured rat cortical neurons.
AB  - The methanol extract of the seeds of Phytolacca americana was reinvestigated to
      yield three new 1,4-benzodioxane-type compounds, americanoic acid methyl ester
      (1), isoamericanoic acid A methyl ester (2), and 9'-O-methylamericanol A (3)
      along with the previously isolated neolignans 6-9. The structures of 1-3 were
      characterized by 2D NMR and long-range selective proton-decoupling (LSPD)
      techniques. The neuritogenic effects of compounds 1-3, and dicarboxilic acids 4
      and 5, which had been previously synthesized with horseradish peroxidase
      catalyzed oxidative coupling of caffeic acid, were examined in primary cultured
      rat cortical neurons. Americanoic acid A methyl ester (1) exhibited neurite
      outgrowth-promoting activity at concentration of 0.01-1.0 microM, whereas
      dicarboxilic acids 4 and 5 were found to induce neuritogenesis dose dependently
      at the concentrations from 0.1 microM to 10 microM.

PMID- 14646314
TI  - Quantitative analysis of ephedrine analogues from ephedra species using 1H-NMR.
AB  - Four ephedrine analogues such as ephedrine, pseudoephedrine, methylephedrine, and
      methylpseudoephedrine were determined by (1)H-NMR from Ephedra species. In the
      region of delta 5.0-4.0, the signals of H-1 attached to the same carbon with a
      hydroxyl, were well separated from each other in CDCl(3). The amount of each
      alkaloid was calculated by the relative ratio of the intensity of H-1 signal to
      the known amount of internal standard, 200 microg of anthracene. This method
      allows rapid determination of the quantity of four ephedrine alkaloids from
      Ephedra species. The amount of these alkaloids was in the range of 1.0-2.0% of
      dry weight depending on the plant materials.

PMID- 14646315
TI  - Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors
      bearing 4-guanidino-Neu5Ac2en derivatives.
AB  - Polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives on a
      poly-L-glutamine backbone are described. Aiming for a longer retention time of 4
      guanidino-Neu5Ac2en (zanamivir) in bronchi and lungs, we focused on
      supermolecules bearing 4-guanidino-Neu5Ac2en derivatives bound at their C-7
      position through noncleavable alkyl ether linkages. We first found that
      alkylation of the 7-hydroxyl group of sialic acid derivative 8 proceeded
      smoothly, and produced 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives 13, which
      exhibited equipotent inhibitory activity against not only influenza A virus
      sialidase but also influenza A virus in the cell culture. Next, we synthesized
      poly-L-glutamine bearing 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives linked by
      amide bonds, 26, which showed enhanced antiviral activity against influenza A
      virus and more potent efficacy in vivo relative to a monomeric sialidase
      inhibitor.

PMID- 14646316
TI  - Preparation of deuterated methyl and dimethyl substituted nicotinoylating agents
      for derivatization of the N-terminal of protein.
AB  - Methyl groups of 6-methylnicotinic acid and 2,6-dimethylnicotinic acid were
      deuterated by an H-D exchange reaction under conditions of 1% NaOD/D(2)O on
      heating. With a condensation reaction between the D-labeled nicotinic acid
      derivative and N-hydroxysuccinimide with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide hydrochloride, the nicotinoylating agents, 1-(6
      methyl[D(3)]nicotinoyloxy)succinimide (2c) and 1-(2,6
      dimethyl[D(6)]nicotinoyloxy)succinimide (2f) were prepared. Both D-labeled
      nicotinoylating agents and their unlabeled counterparts quantitatively modified
      the N-terminal of protein.

PMID- 14646318
TI  - A novel 3,4-bis(sulfenyl)- or 4-selenenyl-3-sulfenylpenta-2,4-dienylation of
      aldehydes using 4-ethoxy-1,2-bis(sulfenyl)- or 1-Selenenyl-2-sulfenyl-buta-1,3
      dienyl lithiums.
AB  - 3,4-Dichalcogenopenta-2,4-dienylation of aldehydes proceeded in good to high
      yields using 4-ethoxy-1-(benzenesulfenyl)-2-(methanesulfenyl)- (5), 4-ethoxy-1,2
      bis(benzenesulfenyl)but-1,3-diene (6), and 1-selenenyl derivatives 7 and 8. This
      novel four-carbon homologation could be applied to a synthesis of 3,4,7,8
      tetrakis(benzenesulfenyl)-10,10-dimethylundeca-2,4,6,8-tetraenal (20).

PMID- 14646317
TI  - Stereostructure of komodoquinone A, a neuritogenic anthracycline, from marine
      Streptomyces sp. KS3.
AB  - The absolute stereostructure of komodoquinone A (1), a neuritogenic
      anthracycline, which was isolated from a cultured marine Streptomyces sp. KS3,
      has been determined on the basis of chemical derivatization. Komodoquinone A (1)
      induces neuronal cell differentiation in the neuroblastoma cell line, Neuro 2A
      and arrests the cell cycle at the G1 phase. The effect of a solid-state medium on
      the production of 1 and its aglycone, komodoquinone B (2), was examined.

PMID- 14646319
TI  - Synthesis and biological evaluation of ebselen and its acyclic derivatives.
AB  - Five ebselen and three acyclic ebselen derivatives were synthesized. These
      compounds were screened for their glutathione peroxidase (GSH Px)-like activity
      and scavenging activity against 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and
      peroxynitrite radical. All tested compounds displayed similar significant GSH Px
      like activity, which are slightly higher than that of ebselen. The peroxynitrite
      scavenging activity showed that the acyclic allylseleno 4c was five times more
      potent than ebselen.

PMID- 14646320
TI  - Studies on the constituents of Gardenia species. III. New iridoid glycosides from
      the leaves of Gardenia jasminoides cv. fortuneana Hara.
AB  - Two new iridoid glycosides, 7 beta,8 beta-epoxy-8 alpha-dihydrogeniposide (1) and
      8-epiapodantheroside (2), were isolated, together with six known (3-8) and three
      artifact (9-11) iridoids, from the leaves of Gardenia jasminoides cv. fortuneana
      Hara. Their structures were established based on chemical and spectral data.

PMID- 14646321
TI  - Three novel 5(6-->7)abeoabietane-type diterpenes from the bark of Taiwania
      cryptomerioides.
AB  - Three new 5(6-->7)abeoabietane diterpenes with the uncommon skeleton of fused 6-5
      6 rings were isolated from the bark of Taiwania cryptomerioides designated as
      taiwaniaquinone F (8), taiwaniaquinol C (9) and taiwaniaquinol D (10). Meanwhile,
      two known compounds, taiwaniaquinones A (1) and D (4), were also obtained. Their
      structures were determined principally from spectral evidence.

PMID- 14646322
TI  - Sulfur-containing compounds from Clinacanthus siamensis.
AB  - Two new sulfur-containing compounds, trans-3-methylsulfonyl-2-propenol (1) and
      trans-3-methylsulfinyl-2-propenol (2) were isolated together with trans-3
      methylthioacrylamide (3), entadamide A (4) and entadamide C (5) from the leaves
      of Clinacanthus siamensis. The structures were established on the basis of the
      spectroscopic data. The compounds were tested for antimalarial and
      antimycobacterial activity.

PMID- 14646323
TI  - Urinary metabolites of nobiletin orally administered to rats.
AB  - During the course of our systematic investigation of the metabolism of
      flavonoids, the polymethoxyflavone nobiletin, occurring in the fruits of Citrus
      depressa, was orally administered to rats. The urinary metabolites were separated
      and identified by three-dimensional HPLC equipped with a photodiode array
      detector and the structure was determined by spectroscopic methods to be 4'
      hydroxy-3',5,6,7,8-pentamethoxyflavone (1).

PMID- 14646324
TI  - Briarane derivatives from the gorgonian coral Junceella fragilis.
AB  - A new trihydroxyl briarane-type diterpenoid, junceellolide H (1), along with two
      known compounds, praelolide (2) and junceellin (3), have been isolated from the
      gorgonian coral Junceella fragilis. The structure, including the relative
      configuration of the new diterpenoid 1, was elucidated by extensive spectroscopic
      methods.

PMID- 14646325
TI  - Lupane-triterpene carboxylic acids from the leaves of Acanthopanax trifoliatus.
AB  - Two new lupane-triterpene carboxylic acids, called acantrifoic acid A (1) and
      acantrifoside C (2) have been isolated from the leaves of Acanthopanax
      trifoliatus. Based on extensive 1D and 2D NMR spectroscopic data, their chemical
      structures were determined as 3 alpha-acetoxy-30-hydroxylup-20(29)-ene-23,28
      dioic acid and 3 alpha-acetoxy-30-hydroxylup-20(29)-ene-23,28-dioic acid 28-O
      alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl ester.

PMID- 14646326
TI  - Further studies on the structure of polysaccharides from the lichen Flavoparmelia
      caperata (L.) Hale.
AB  - A water-soluble polysaccharide called PC-2 was previously isolated from
      Flavoparmelia caperata (L.) Hale and assigned to alpha(1-3)(1-4)glucan. However,
      PC-2 separated into three components, PC-2A, PC-2B, and PC-2C (a single peak in
      HPLC, respectively) on further purification. Methylation analysis and (1)H- and
      (13)C-NMR spectroscopic studies suggested that PC-2A is composed of repeating
      units of [alpha-D-Glc1-3](3), : [alpha-D-Glc1-4](2), while PC-2B and PC-2C are
      partly branched galactoglucomannans consisting of (1-3)- and (1-4)-linked alpha-D
      glucopyranosyl units as the main chain. In addition we confirmed that the
      polysaccharide fraction PB-2 from the lichen of the same genus, Flavoparmelia
      baltimorensis (Gyelink & Foriss) Hale, is identical to PC-2 based on the chemical
      and spectroscopic data.

PMID- 14646327
TI  - Constituents of Hypericum laricifolium and their cyclooxygenase (COX) enzyme
      activities.
AB  - Investigation of the aerial parts of the medicinal plant Hypericum laricifolium
      led to the isolation of two new natural products, hentriacontanyl caffeate (1a),
      nonacosanyl caffeate (1b). In addition, stigmasterol, beta-sitosterol, 3-epi
      betulinic acid (2), caffeic acid (3), ferulic acid, docosanol, p-hydroxybenzoic
      acid, 3,4-dimethoxy benzoic acid, quercetin (4), quercetin-3-O-galactoside (5),
      quercetin-3-O-rutinoside (6), quercetin-3-O-rhamnoside (7), quercetin-3-O
      glucuronide (8) and shikimic acid were also isolated. The structures were
      determined by 1D- and 2D-NMR, mass spectrometry, and chemical transformations.
      The anti-inflammatory effects of the isolated compounds were discussed briefly.

PMID- 14646328
TI  - Tyromycic acids F and G: two new triterpenoids from the mushroom Tyromyces
      fissilis.
AB  - Phytochemical examination of the methanol extract of the fruit bodies of the
      Japanese fungus Tyromyces fissilis led to the isolation of two new lanostane
      derivatives called tyromycic acids F (1) and G (2), together with two known
      compounds, tyromycic acid (3) and trametenolic acid B (4). Their structures were
      identified by 2D NMR, IR, and UV spectroscopy.

PMID- 14646329
TI  - Spectrophotometric determination of some drugs for osteoporosis.
AB  - Three simple, accurate and sensitive spectrophotometric methods are developed for
      the determination of some new drugs for the treatment of osteoporosis:
      risedronate sodium (I), alendronate sodium (II) and etidronate disodium (III).
      The first method is based on the measurement of difference in absorbance (Delta
      A) of risedronate sodium in 0.01 mol l(-1) hydrochloric and 0.1 mol l(-1) sodium
      hydroxide at 262 nm. Beer's law is obeyed over a concentration range of 15-150
      microg ml(-1) with mean recovery 99.75+/-1.22 and molar absorptivity (epsilon)
      1.891 x 10(3). The second method is based on the reaction of the primary amino
      group of (II) with ninhydrin reagent in methanolic medium in the presence of 0.05
      mol l(-1) sodium bicarbonate. The colored product is measured at 568 nm, and the
      linearity range is found to be 3.75-45 microg ml(-1) with mean recovery 99.77+/
      0.73 and epsilon 9.425 x 10(3). The third method is based on oxidation of the
      three mentioned drugs with ceric (IV) sulphate in 0.5 mol l(-1) sulphuric acid at
      room temperature and subsequent measurement of the excess unreacted cerium (IV)
      sulphate at 320 nm. The method obeyed Beer's law over a concentration range of 2
      24 microg ml(-1) for the three drugs with mean recovery 99.79+/-1.16, 99.73+/
      1.38 and 99.86+/-1.13 and epsilon 14.427 x 10(3), 13.813 x 10(3) and 14.000 x
      10(3) for drugs I, II, III respectively. The proposed methods were successfully
      applied for the determination of the studied drugs in bulk powder and in
      pharmaceutical formulations. The results were found to agree statistically with
      those obtained the reported methods. Furthermore, the methods were validated
      according to USP regulations and also assessed by applying the standard addition
      technique.

PMID- 14646330
TI  - Inhibitory effects of 3-O-acyl-(+)-catechins on Epstein-Barr virus activation.
AB  - In the course of an exploratory investigation of antitumor-promoting catechins, 3
      O-acyl-(+)-catechins of varying carbon lengths from C(4) to C(18) were assessed
      for inhibitory effects on the activation of the Epstein-Barr virus early antigen.
      Like 3-O-acyl-(-)-epigallocatechins, the (+)-catechin derivatives showed
      promising effects with the C-3 acyl chain of C(8)-C(11) carbon atoms.

PMID- 14646331
TI  - Synthesis of pyrimidine derivatives possessing an antioxidative property and
      their inhibitory effects on picryl chloride-induced contact hypersensitivity
      reaction.
AB  - We conducted a preliminary structure-activity relationship (SAR) study of some
      barbituric acid and uracil derivatives against the picryl chloride-induced
      contact hypersensitivity reaction. The introduction of an antioxidative moiety to
      the side chain of the C(6)-position of uracil was effective against this model.
      The introduction of dimethoxyphenol (8b) or dimethylphenol (8c) instead of di-t
      butylphenol (8a) as an antioxidative moiety gave diminished activities, so, the
      reactive oxygen would contribute to the inflammation of this model, and an
      antioxidative activity was required for exhibiting the inhibitory activity. The
      inhibitory activity was significantly affected by the substituent at the N(1)
      phenyl moiety.

PMID- 14646332
TI  - Effect of surface covering of lactose carrier particles on dry powder inhalation
      properties of salbutamol sulfate.
AB  - The effect of the surface covering of lactose carrier particles on the dry powder
      inhalation properties of salbutamol sulfate was investigated. Lactose carrier
      surfaces were covered with sucrose tristearate (J-1803F) by a high-speed
      elliptical-rotor-type powder mixer (Theta-Composer). In the present study,
      drug/carrier powder mixtures were prepared consisting of micronized salbutamol
      sulfate and lactose carriers with various particle surface conditions prepared by
      surface covering. These powder mixtures were aerosolized by a Jethaler), and the
      in vitro inhalation properties of salbutamol sulfate were evaluated by a twin
      impinger. Compared with the powder mixed with uncovered lactose carrier, the in
      vitro inhalation properties of the powder mixture prepared using the surface
      covering lactose carrier were significantly different, showing that the in vitro
      inhalation properties of salbutamol sulfate were improved. In vitro inhalation
      properties increased with the percentage of J-1803F added. Using this surface
      covering system would thus be valuable for increasing the inhalation properties
      of dry powder inhalation with lactose carrier particles.

PMID- 14646333
TI  - Microbial transformation of terreusinone, an ultraviolet-A (UV-A) protecting
      dipyrroloquinone, by Streptomyces sp.
AB  - Biotransformation study was conducted on the marine dipyrroloquinone,
      terreusinone (1) isolated from the marine-derived fungus Aspergillus terreus.
      Preparative-scale fermentation of terreusinone with Streptomyces sp. has resulted
      in the isolation of a new oxidized metabolite, terreusinol (2). The structure was
      elucidated as 2-[(1R)-1-hydroxyisobutyl]-6-[(1R)-1,2-dihydroxyisobutyl]-1H,5H
      pyrrolo[2,3-b]indole-4,8-dione (2) on the basis of physicochemical evidence.
      Terreusinol (2) showed an ultraviolet-A (UV-A) (320-390 nm) protecting activity
      with ED(50) values of 150 microM, which is more active than oxybenzone (ED(50),
      350 microM) currently being used as sunscreen.

PMID- 14646334
TI  - Vitamin B12 is a strong determinant of low methionine synthase activity and DNA
      hypomethylation in gastrectomized rats.
AB  - BACKGROUND/AIMS: The respective influence of folate and vitamin B12 deficiency on
      MTR activity and transcription, and on DNA methylation is not clearly
      established. The aim of this study was to assess the respective influence of
      folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA
      methylation. METHODS: Sixty-one rats were administered normal diet or diet
      deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them
      underwent total gastrectomy or ileal resection. RESULTS: Low vitamin B12 was
      observed only in gastrectomized rats. Low folate was observed in rats under
      deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with
      vitamin B12 level <200 pmol/l (p=0.0002), while the ratios of total vs. holo-MTR
      activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12
      was the single determinant of low MTR (lower quartile, odds ratio=15.75,
      p=0.0017). Low MTR and low vitamin B12 were the two determinants of DNA
      hypomethylation (lower quartile) (odds ratio=17.07, p=0.0006, and odds
      ratio=7.31, p=0.006, respectively). CONCLUSION: Vitamin B12 affects MTR
      expression by a non-transcriptional mechanism different from a protective effect
      on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.

PMID- 14646335
TI  - Rising incidence of reflux oesophagitis in patients undergoing upper
      gastrointestinal endoscopy.
AB  - BACKGROUND: In the literature a lot of epidemiological data is present but little
      is known on the yearly incidence of oesophagitis and Barrett's oesophagus. For
      this reason a cross-sectional study was done to explore the yearly incidence of
      these conditions in patients sent for upper gastrointestinal endoscopy. METHODS:
      All patients diagnosed with reflux oesophagitis, Barrett's oesophagus or hiatus
      hernia in a 10-year period were included. RESULTS: In the period of 10 years
      11,691 consecutive patients underwent endoscopic examination. Oesophagitis was
      diagnosed in 1,633 patients, Barrett's oesophagus in 275, and hiatus hernia
      without oesophagitis in 1,407 patients. The number of patients with oesophagitis
      almost doubled, while the number of patients with hiatus hernia or Barrett's
      oesophagus remained constant each year in this time period. The number of men
      diagnosed with oesophagitis or Barrett's oesophagus was significantly higher than
      the number of women. Hiatus hernia occurred significantly more often in women,
      and was present in 79-88% of patients with active reflux oesophagitis.
      CONCLUSION: This study clearly shows that the incidence of reflux oesophagitis
      shows a marked increase. The incidence doubled in a period of ten consecutive
      years. This data should be kept in mind in planning future health-care resources.
      It can be expected that the use of acid suppressive therapy will be rising in the
      years to come.

PMID- 14646336
TI  - Platelet-activating factor concentration in the stool of human newborns: effects
      of enteral feeding and neonatal necrotizing enterocolitis.
AB  - Epidemiologic studies have identified enteral feedings as a risk factor for
      necrotizing enterocolitis (NEC). Enteral feedings provide the substrate for
      colonization of the newborn gut with gram-negative bacteria with endotoxin
      production, which may trigger the production of endogenous inflammatory
      mediators, including platelet-activating factor (PAF). In this prospective study,
      we examined the effect of enteral feeding on PAF concentration in the stool of
      preterm and full-term human newborns. The concentration of PAF levels in stool
      was measured at the following times: at passage of first meconium, within 24 h
      prior to the onset of feedings, at the 3rd and 14th day of feeding and at any
      time confirmed NEC developed. Stool samples also were analyzed for levels of
      acetylhydrolase, the PAF breakdown enzyme. Stool PAF concentration rose
      significantly following the start of enteral feedings. The mean PAF concentration
      for day 14 samples was significantly higher than the mean concentration of
      meconium samples (4.90 +/- 1.03 vs. 1.81 +/- 0.38 ng/g, p < 0.05) and day 0
      samples (4.90 +/- 1.03 vs. 1.79 +/- 0.39 ng/g, p < 0.05). For the 7 patients
      diagnosed with definite NEC, the mean stool PAF concentration was 12.42 +/- 0.77
      ng/g, significantly elevated compared to the mean PAF levels in stool from
      healthy infants at all sampling times (p < 0.01). There was no significant change
      in acetylhydrolase activity at any of the sampling times. Stool PAF concentration
      increases with the provision of enteral feedings and rises further with the
      development of NEC. Since stool acetylhydrolase activity remained unchanged, we
      speculate the increase of PAF in stool likely represents increased PAF production
      at the local level following the provision of enteral feedings or the development
      of neonatal necrotizing enterocolitis.

PMID- 14646337
TI  - Abnormal intestinal histology in neonates with congenital anomalies of the
      gastrointestinal tract.
AB  - In animal models, when swallowing is experimentally prevented in utero, bowel
      length and weight are reduced, and villus height, crypt depth, and villus
      function are retarded. Little is known about the intestinal histology in infants
      with gastrointestinal (GI) tract anomalies. We examined the histological
      architecture of the intestine in neonates with GI anomalies in comparison to that
      of normal fetuses. Villus height, area, and length and crypt depth of normal
      fetuses were quantified in the proximal small bowel (n = 11) and measurements
      compared to those of surgical specimens of neonates with congenital anomalies of
      the GI tract (n = 16). Villus height and area and lamina propria height and area
      increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of
      the GI tract, the villi were blunted and lacked normal histological architecture,
      the crypts were disorganized, and the crypt depth was significantly decreased (p
      = 0.004). Enterocyte height and area were significantly greater in neonates with
      congenital anomalies of the GI tract. The intestinal histology in neonates with
      congenital anomalies of the GI tract differs significantly from that of normal
      fetuses.

PMID- 14646338
TI  - Translocation of coagulase-negative bacterial staphylococci in rats following
      intestinal ischemia-reperfusion injury.
AB  - Many patients with sepsis have bacteremia for which no septic focus is identified
      either clinically or by autopsy. This study was designed to determine the
      relationship between the ischemia-reperfusion injury (IRI) and bacterial
      translocation that might be involved in the pathogenesis of necrotizing
      enterocolitis. In the first experiment, a total of 32 Sprague-Dawley rats
      weighing 150-200 g were divided into four groups. The mesentery to isolated loop
      was occluded for 30, 60, and 90 min following 30-min reperfusion in the three
      groups of experimental animals with a micro-bulldog clamp. A control group
      involved the same technique and exposure, without occlusion of the mesentery. Two
      sets of blood culture were taken through a catheter in the portal vein
      immediately and 15 min after the reperfusion, respectively. In another
      experiment, bacteria isolated were fed in different doses to control rats and
      those after 30- or 60-min ischemia and 30-min reperfusion. Two sets of blood
      culture were taken following the procedure. Invasion and transcytosis of the
      bacteria through epithelial cells were studied in vitro using a Madin-Derby
      canine kidney (MDCK) cell monolayer model. PCR for delta toxin gene was performed
      on all bacteria isolated, using Staphylococcus epidermidis as the control.
      Coagulase-negative staphylococci (CoNS) were invariably isolated from mice with
      prolonged ischemia (90 min) and reperfusion. When bacteria were fed into mice
      with only 30-min ischemia, an inoculum as low as 5 x 10(5) CFU/ml could induce
      bacteremia. No bacterial translocation was found in control mice even fed with a
      higher dose of bacteria (5 x 10(8) CFU/ml). In vitro experiments showed that CoNS
      failed to transcytose MDCK monolayer. These isolates were not cytotoxic to MDCK
      cells and contained no delta toxin gene. Bacterial translocation of CoNS occurred
      following severe bowel ischemia and reperfusion injury. Intact mucosa integrity
      readily prevented bacterial translocation; however, bacterial translocation could
      occur in rats following mild IRI in the presence of a higher number of CoNS in
      the gut.

PMID- 14646339
TI  - Elevated blood levels of endogenous ouabain-like factor in preterm versus mature
      newborns at birth.
AB  - Compared to healthy adults, elevated levels of endogenous ouabain-like factor
      (OLF) have already been shown in the cord blood, and a role of OLF in the
      maintenance of high Na(+) excretion by reducing tubular sodium reabsorption
      during intrauterine life was suggested. In this study, we aimed to measure OLF
      cord blood levels of premature and mature newborns to provide further data on the
      possible physiological significance of this compound in neonates. OLF was
      assessed in the cord blood of newborns (28-41 weeks) and in the blood of healthy
      adults using ouabain radioimmunoassay. HPLC was employed to isolate endogenous
      OLF. Newborns had about twelve times higher OLF levels than healthy adults (41.96
      +/- 4.64 vs. 3.1 +/- 1.1 pg/ml, p < 0.001). Further, there was a highly
      significant correlation (p < 0.004) between maturity and OLF concentration; OLF
      level increased with gestational age, however there was a rapid drop in its
      concentration at week 39 (43.26 +/- 7 vs. 35.47 +/- 1.84 pg/ml, p = NS). Further
      studies are needed to evaluate the physiological relevance of higher OLF in
      preterm versus mature newborns.

PMID- 14646340
TI  - The association of metabolic disorders with the metabolic syndrome is different
      in men and women.
AB  - AIMS: Metabolic disorders depend on genetic, hormonal and environmental factors,
      whose relations may differ between genders. Therefore, we compared the
      contribution of metabolic disorders to the metabolic syndrome in women and men.
      METHODS: To this end, we used a hierarchical classification statistical method to
      classify subjects into similarity groups according to clinical and biological
      parameters. Data were collected from 3,508 men and women aged 35-64 years, from a
      cardiovascular disease survey. RESULTS: In both women and men, hierarchical
      classification identified a cluster corresponding to the metabolic syndrome
      representing 14 and 15% of the women's and men's sample, respectively. In women,
      elevated body weight (women's Z-score: 1.59 vs. men's Z-score: 1.29; p < 0.005),
      waist girth (1.62 vs. 1.30; p < 0.001) and low HDL cholesterol (-0.95 vs. -0.75;
      p < 0.05) were significantly larger contributors to the metabolic syndrome than
      in men. In contrast, systolic (0.59 vs. 0.95; p < 0.0001) and diastolic (0.55 vs.
      0.99; p < 0.0001) blood pressure and apolipoprotein B (0.51 vs. 0.71; p < 0.0001)
      contributed significantly less in women than in men. Finally, insulin (n.s.),
      glucose (n.s.), triglycerides (n.s.) and LDL-cholesterol (n.s.) contributions
      were not different between genders. CONCLUSION: These results are consistent with
      the concept that a clustering of metabolic disorders occurs frequently in both
      women and men. However, the contribution of several metabolic disorders to the
      metabolic syndrome is different in men and women. This finding supports the
      concept that different criteria are necessary to define the metabolic syndrome in
      women and men.

PMID- 14646341
TI  - Effect of dietary docosahexaenoic acid and catechins on maze behavior in mice.
AB  - BACKGROUND/AIMS: Docosahexaenoic acid (DHA; 22:6 n-3) and catechins are food
      components that play an important role in maintaining human health. However, the
      effect of a simultaneous intake of DHA and catechins on brain function is
      unknown. The purpose of this study was to investigate the effect of DHA and
      catechins on maze behavior in mice. METHOD: Adult (5 months old) and old (15
      months old) male mice were fed 5% lard diets containing 0 or 1.5% DHA ethyl ester
      (DHA-EE), either with or without 0.5% catechins, for 3.5 months. Maze behavior
      was assessed 3 months after the start of the feeding experiment. The time
      required and distance traveled to reach the maze exit, and the number of times
      that a mouse strayed into blind alleys in the maze were measured. The fatty acid
      compositions of plasma and brain lipids were measured after the maze behavior
      experiment. RESULTS: Adult mice in the catechin, DHA-EE, and DHA-EE + catechin
      diet groups required less time and traveled a shorter distance to reach the maze
      exit, and strayed into blind alleys fewer times than those in the corresponding
      lard groups. Among old mice, the DHA-EE + catechin diet group showed an
      improvement in maze behavior. No marked differences in the brain fatty acid
      composition between lard and catechin diet groups were observed; in the DHA-EE
      intake groups, the brain DHA percentage was raised. CONCLUSION: These results
      suggest that a simultaneous intake of DHA and catechins may certainly enhance
      brain function in both adult and old mice.

PMID- 14646342
TI  - Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial
      intermembrane space proteins in apoptotic cell death.
AB  - In addition to their function as major energy-providing organelles of the cell,
      mitochondria accomplish a crucial role in apoptosis. The pro-apoptotic BH3-only
      members of the Bcl-2 family continuously sense the cellular integrity and well
      being at various subcellular levels. If these sentinels are induced, released or
      activated, they converge on the release of mitochondrial intermembrane space
      proteins such as cytochrome c, the oxidoreductase AIF, endonuclease G,
      Smac/DIABLO and the serine protease Omi/HtrA2. We discuss how Bcl-2 family
      members integrate diverse survival and death signals and act as central
      regulators of apoptosis. Furthermore, we describe the current knowledge on the
      role of mitochondrial proteins in apoptotic cell death, discuss the molecular
      mechanisms of their release and the apoptotic role of mitochondria from a
      phylogenetic and immunological point of view.

PMID- 14646343
TI  - Granzyme B-induced cell death.
AB  - Granzyme B (GrB) is a serine protease that is released by cytotoxic lymphocytes
      to kill virus-infected and tumor cells. Recent advances in the understanding of
      GrB have stressed the importance of reassessing the mechanisms by which GrB
      accomplishes its death functions. These include the uptake and trafficking of GrB
      within target cells, pathways used to trigger cell death, and the mechanism(s)
      controlling its killing activity. In addition, the role that GrB plays in human
      pathologies is still to be defined. The purpose of this review is to discuss
      recent insights into the biology of GrB and to evaluate its functional
      significance in health and disease.

PMID- 14646344
TI  - Regulation of cell death in the lymphoid system by Bcl-2 family proteins.
AB  - Programmed cell death is an ordered process that is essential for the normal
      development and homeostasis of an organism. Dysregulation of this programmed
      pathway, resulting in either excess cell numbers or unscheduled cell death,
      underlies a number of disease states. Bcl-2 family proteins play a key role in
      regulating cell death and survival, and a number of studies have demonstrated
      their role as important regulators of cell fate in the lymphoid system. Mice that
      are genetically deficient or overexpress various Bcl-2 family proteins have
      provided important clues regarding their roles in lymphocyte development,
      progression of lymphoid tumors and analogous human disorders. In addition,
      lymphotropic viruses may trigger cell proliferation and inhibit cell death with
      the help of their own Bcl-2 homologues. Comparing the shared and distinct
      functions of viral and cellular Bcl-2-related proteins yields new insight into
      their fundamental mechanisms.

PMID- 14646345
TI  - Apoptosis of neutrophils.
AB  - Regulation of the neutrophil life span by apoptosis provides a fine balance
      between their function as effector cells of host defense and a safe turnover of
      these potentially harmful cells. Alterations of neutrophil apoptosis are
      associated with a number of diseases. As do other cell types, neutrophils possess
      components of both extrinsic and intrinsic apoptotic routes. The intrinsic
      pathway of apoptosis seems to be of major importance in neutrophils since they
      are programmed for a rapid spontaneous cell death. However, in neutrophils this
      mechanism of apoptosis has special features, probably due to peculiarities of
      neutrophil mitochondria, which are believed to be a core regulator of intrinsic
      cell death. A better understanding of mechanisms underlying neutrophil cell death
      would help to understand neutrophil physiology and contribute to the search of
      new approaches for handling of pathology related to disturbances in neutrophil
      apoptosis and also increase our knowledge of inflammation in general.

PMID- 14646346
TI  - Role of apoptotic processes in platelet biogenesis.
AB  - Platelets are anucleate cells that fragment from mature megakaryocytes and play
      an essential role in thrombosis and hemostasis. Platelets are among the first
      cell types to be recruited to an injured blood vessel, assisting in endothelial
      repair. Platelet hyperactivation contributes to the development of
      atherosclerosis, myocardial infarction, and ischemia of peripheral limbs. A fall
      in platelet counts, due to a variety of conditions, including disseminated
      intravascular coagulation, chemotherapy or genetic disorders, may lead, in most
      severe cases, to death from hemorrhage. This review focuses on the late stages of
      megakaryocyte differentiation and platelet fragmentation, including associated
      cytoskeletal changes, and on the importance of apoptotic events for these
      processes. Studies point to a unique biological system in which programmed cell
      death may be linked with biogenesis of new cells.

PMID- 14646347
TI  - The myelodysplastic syndromes: a matter of life or death.
AB  - Apoptosis is upregulated in early myelodysplastic syndromes (MDS) and may
      contribute to the peripheral cytopenias commonly observed. Conversely, leukemic
      progression is associated with abrogation of programmed cell death (PCD). The
      stage of hematopoietic cell maturation at which defects in PCD arise and the
      underlying causes of apoptosis dysregulation remain unknown. This paper outlines
      the apoptotic process in normal hematopoietic cells and summarizes current data
      regarding the role, potential causes and clinical implications of altered
      apoptosis in MDS.

PMID- 14646348
TI  - p53 alterations in myeloid leukemia.
AB  - Although most solid tumors contain inactivating mutations of the p53 tumor
      suppressor, hematological malignancies do not contain frequent alterations in the
      p53 gene (<20%). How these tumors arise in the presence of a super tumor
      suppressor like p53 remains to be elucidated. Given the number of downstream
      effectors of p53, it is likely that critical targets of p53 are inactivated in
      leukemia, bypassing the requirement for p53 gene mutations in these tumors. This
      review describes new biochemical and transcriptional activities of p53 as well as
      the status of p53 in acute myelogenous leukemia and chronic myelogenous leukemia.

PMID- 14646349
TI  - Apoptosis induced by molecular targeting therapy in hematological malignancies.
AB  - Molecular targeting therapies for hematological malignant diseases such as
      monoclonal antibodies and small molecules have been reviewed. Imatinib mesylate
      (STI571) targets the tyrosine kinase activity of the BCR-ABL fusion protein in
      CML, and was superior to IFN-alpha plus low-dose cytarabine in newly diagnosed
      chronic-phase CML in a phase III randomized study. Imatinib induced apoptosis in
      BCR-ABL-positive cells in vitro, and activates several signaling pathways such as
      PI3K/Akt, STAT5 and Ras/MAPK. Combination therapies with imatinib and new
      strategies for downregulation of intracellular BCR-ABL protein levels have also
      been investigated from the phenomenon of resistance to imatinib. Anti-CD20
      (rituximab) became the first monoclonal antibody approved for the treatment of a
      relapsed/refractory follicular/low-grade NHL and promising results were obtained
      from a phase III randomized study. Although antibody-dependent cell-mediated
      cytotoxicity and complement-mediated cytotoxicity are likely to be the major
      effectors of B-cell depletion in vivo, direct cytotoxicity by CD20 monoclonal
      antibody on B-cell lines in vitro has been reported. Anti-CD33 (Mylotarg) and
      FLT3 inhibitors for AML have also been used in clinical trials and signaling
      pathways induced by these agents are under intensive investigation. Arsenic
      trioxide, like all-TRANS-retinoic acid (ATRA), downregulates promyelocytic
      leukemia protein/retinoic acid receptor-alpha (PML/RARalpha) fusion protein and
      induced apoptosis in APL cells, and promising results were obtained from ATRA
      resistant APL patients. Finally we show our promising in vitro and in vivo data
      of R-etodolac (a non-steroidal anti-inflammatory drug lacking cyclooxygenase
      inhibitor activity) against chronic lymphocytic leukemia (CLL) cells.

PMID- 14646350
TI  - Effect of stobadine on leukocyte free radical generation in streptozotocin
      diabetic rats: comparison with vitamin E.
AB  - We investigated a possible alteration in the ability of leukocytes to produce
      reactive oxygen species by stobadine, a pyridoindole antioxidant, in
      streptozotocin-diabetic rats. The production of free radicals from whole blood
      was assessed by luminol-enhanced chemiluminescence after stimulation by phorbol
      myristate acetate. The effects of vitamin E treatment were also evaluated and
      compared with the effects of combined treatment with stobadine. Diabetes was
      induced by streptozotocin (55 mg/kg i.p.). Some of diabetic rats and their age
      matched controls were treated orally with a low dose of stobadine (24.7
      mg/kg/day), vitamin E (400-500 IU/kg/day), or stobadine plus vitamin E for 10
      weeks. Stobadine and vitamin E separately produced, to a similar degree, a
      reduction in diabetes-induced hyperglycemia. The phorbol myristate acetate
      stimulated chemiluminescence signal was markedly depressed in both moderate and
      severe diabetic rats. Stobadine treatment prevented this depression of the
      chemiluminescence response. Vitamin E treatment also eliminated the depression of
      the chemiluminescence signal in diabetic rats, and the combination with stobadine
      did not produce further improvement in leukocyte function. These results suggest
      that stobadine treatment alone is able to produce beneficial effects on leukocyte
      function and to maintain leukocyte free radical release during diabetes.

PMID- 14646351
TI  - Inhibition of guinea pig intestinal peristalsis by the flavonoids quercetin,
      naringenin, apigenin and genistein.
AB  - Flavonoids are known to relax precontracted intestinal smooth muscle and to delay
      intestinal transit. We therefore investigated the effects of quercetin,
      naringenin, apigenin and genistein on intestinal peristalsis in vitro.
      Peristalsis in fluid-perfused segments of the guinea pig small intestine was
      recorded through the intraluminal pressure changes associated with the
      peristaltic waves. Alterations of distension sensitivity were reflected by
      changes in the peristaltic pressure threshold and alterations of peristaltic
      performance by changes in the maximal acceleration, amplitude and residual
      baseline pressure of the peristaltic waves. Quercetin, naringenin, apigenin and
      genistein (10-300 micromol/l) depressed intestinal peristalsis in a structure-
      and concentration-dependent manner. The flavonoid-evoked changes in peristalsis
      parameters made it possible to distinguish between two patterns of peristaltic
      motor inhibition: a decrease in distension sensitivity and peristaltic
      performance (apigenin and genistein) and a decrease in distension sensitivity
      without a major change in peristaltic performance (quercetin and naringenin). The
      antiperistaltic effect of quercetin was partially prevented by apamin (0.5
      micromol/l), N-nitro-L-arginine methylester (100 micromol/l) and naloxone (0.5
      micromol/l), whereas the effect of genistein was hardly affected by these drugs.
      Peristaltic motor activity suppressed by quercetin (300 micromol/l), but not
      genistein (100 micromol/l), was partially restored by apamin. In contrast,
      neostigmine (0.3 micromol/l) caused a significant recovery of peristalsis from
      blockade by genistein but failed to reverse peristaltic motor blockade due to
      quercetin. These observations suggest that naringenin and quercetin inhibit
      peristalsis by facilitating inhibitory enteric pathways, whereas apigenin and
      genistein interfere with muscle excitation or excitation-contraction coupling.

PMID- 14646352
TI  - Differential induction of the expression of GST subunits by geniposide in rat
      hepatocytes.
AB  - Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides
      Ellis, has the biological capabilities of detoxication, antioxidation, and
      anticarcinogenesis. In this study, the mechanism of geniposide affecting the GST
      (glutathione S-transferase) system was investigated. Primary cultured rat
      hepatocytes were treated with geniposide and examined for total GST activity and
      expression of GST subunits. The results showed that the geniposide-induced GST
      activity was dose and time dependent. Western blotting data demonstrated that
      geniposide induced increased protein levels of GSTM1 and GSTM2 (approximately 1.7
      and 1.8-fold of control, respectively), but did not increase those of GSTA1. The
      corresponding transcripts levels were confirmed by RT-PCR. Using PD98059, the
      effect of geniposide was verified to be via the MEK pathway. The results suggest
      that geniposide possesses a potential for detoxication by inducing GST activity
      via increasing the transcription of GSTM1 and GSTM2.

PMID- 14646353
TI  - Pharmacokinetics and the cardiovascular effects of irbesartan in aortic
      coarctated rats.
AB  - A pharmacokinetic-pharmacodynamic study of irbesartan (IRB) was performed in
      anesthetized sham-operated (SO) and aortic coarctated (ACo) rats. Anesthetized
      Wistar rats were used 7 days after ACo procedure or SO. A vascular shunt probe
      was inserted into the carotid artery for the study of plasma pharmacokinetics. In
      a separate experiment, a concentric probe was placed into the anterior
      hypothalamus for the study of the IRB distribution in the central nervous system.
      IRB (10 mg.kg(-1) i.v.) induced a rapid decrease of the heart rate (HR) in the
      ACo animals (Delta HR -19.2 +/- 2.0 bpm, n = 6; p < 0.05 vs. basal HR), but not
      in the SO rats (Delta HR -6.7 +/- 5.1 bpm, n = 6). Moreover, IRB reduced the mean
      arterial blood pressure in the animals of both experimental groups, but the
      hypotensive effect lasted longer in ACo rats than in SO animals. Analysis of
      blood samples showed a lower constant of elimination of IRB in ACo rats (Ke 0.67
      +/- 0.28 h(-1), n = 5; p < 0.05) than in SO rats (Ke 1.72 +/- 0.30 h(-1), n = 6).
      Also, a greater distribution of IRB in the anterior hypothalamus was seen in the
      ACo rats (area under the curve 32 +/- 4 ng.ml(-1).h(-1), n = 6; p < 0.05) than in
      the SO rats (area under the curve 12 +/- 1 ng.ml(-1).h(-1)). The protein binding
      of IRB was similar in both experimental groups (SO rats 7.1 +/- 1.2%, n = 6; ACo
      rats 7.7 +/- 1.5%, n = 6). In conclusion, ACo reduces the plasma elimination of
      IRB, increasing the distribution in the central nervous system. The longer
      hypotensive effect of IRB observed in ACo animals could be explained by the
      slowest elimination of the drug in ACo rats. On the other hand, the effect of IRB
      on the HR suggested that angiotensin II modulates this parameter in ACo animals
      at an early stage of hypertension.

PMID- 14646354
TI  - Evidence for the mechanisms underlying the effects of pimaradienoic acid isolated
      from the roots of Viguiera arenaria on rat aorta.
AB  - The present study examines the effects of the diterpene ENT-pimara-8(14),15-dien
      19-oic acid (PA) on rat thoracic aorta. PA (10(-5), 3 x 10(-5) and 10(-4) mol/l)
      caused concentration-dependent inhibition of phenylephrine (Phe)-induced
      contraction in either endothelium-intact or endothelium-denuded aortic rings. PA
      attenuated the contraction induced by CaCl(2) in Ca(2+)-free solution containing
      Phe (10(-7) mol/l) or KCl (30 mmol/l). This diterpene did not interfere with
      Ca(2+) release from intracellular stores mediated by either Phe (10(-6) mol/l) or
      caffeine (30 mmol/l). PA (10(-6) to 3 x 10(-4) mol/l) concentration dependently
      relaxed Phe-pre-contracted rings with intact (92.64 +/- 7.60%) or denuded
      endothelium (98.82 +/- 1.56%). Pre-incubation of denuded aortic rings with N(G)
      nitro-L-arginine methyl ester (10(-4) mol/l), 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (10(-6) mol/l) or indomethacin (10(-5) mol/l) reduced PA
      induced relaxation (percentage of relaxation: 77.50 +/- 3.95, 78.56 +/- 2.81,
      77.11 +/- 6.22, respectively). However, the relaxant responses induced by PA on
      Phe-pre-contracted rings were unaffected by tetraethylammonium (1 and 5 mmol/l).
      PA also relaxed KCl-pre-contracted rings with intact (97.44 +/- 3.66%) or denuded
      endothelium (95.95 +/- 3.72%). Collectively, these results support the notion
      that the effects elicited by PA on vascular smooth muscle are endothelium
      independent and involve extracellular Ca(2+) influx blocked. In addition, PA
      effects are partly dependent on the release of nitric oxide from the vascular
      smooth muscle through an activation of guanylyl cyclase-dependent mechanism and
      are related to the release of metabolites derived from the arachidonic acid
      pathway. Finally, our results demonstrated that the PA relaxant action is not
      related with the opening of potassium (K(+)) channels.

PMID- 14646355
TI  - Amlodipine increases endothelial nitric oxide by dual mechanisms.
AB  - Several experimental and clinical studies have demonstrated the antiatherogenic
      profile of the long-acting calcium antagonist amlodipine. Given the pivotal role
      of endothelial (dys)function during atherogenesis, we investigated the influence
      of amlodipine on endothelial nitric oxide (NO) bioavailability. Acute addition of
      amlodipine to segments of porcine coronary arteries resulted in a significant
      increase in NO release which could be blocked by the NO synthase inhibitor L-NMMA
      (N-monomethylarginine). This effect was mirrored by a rise in intracellular cGMP
      levels in porcine endothelial cell cultures. Long-term (24 h) treatment of
      porcine endothelial cell cultures with amlodipine (0.1-10 micromol/l)
      significantly enhanced the basal NO formation in a concentration-dependent manner
      which was abrogated in the presence of L-NMMA (0.1 mmol/l). In EA.hy 926
      endothelial cells, amlodipine treatment for 24 h significantly increased the
      endothelial NO synthase protein expression. To evaluate whether the observed
      increase in NO was additionally due to an antioxidative protection of NO, we
      examined the influence of amlodipine in different in vitro models. In a cell-free
      system, amlodipine quenched superoxide anions (hypoxanthine/xanthine oxidase
      assay) at high concentrations (150 micromol/l). Addition of artificial membrane
      preparations (dimyristoylphosphatidylcholine) to mimic a physiological
      environment significantly enhanced this antioxidative effect. In a more
      physiological model of hyperglycemia (30 mmol/l, 20 min) induced formation of
      reactive oxygen species from native endothelial cells of porcine coronary
      arteries, amlodipine concentration dependently attenuated the reactive oxygen
      species release (>60%; 10 micromol/l). We conclude, that amlodipine increases the
      endothelial NO bioavailability, firstly via enhanced NO formation and secondly by
      prolonging the half-life of NO through antioxidative properties. This may result
      in an improved endothelial function.

PMID- 14646356
TI  - Pertussis toxin-sensitive G protein but not NO/cGMP pathway mediates the negative
      inotropic effect of carbachol in adult rat cardiomyocytes.
AB  - Previous studies have shown that muscarinic inhibition of cardiac contractility
      is mediated by either activation of nitric oxide (NO)/guanosine 3',5'-cyclic
      monophosphate (cGMP) pathway or stimulation of inhibitory G protein (G(i)).
      However, it still remains controversial as to whether NO/cGMP pathway or G(i)
      protein or both mediate(s) the negative inotropic effect of muscarinic agonists
      in adult ventricular myocytes. In the present study that involves the use of
      adult rat ventricular myocytes, the muscarinic agonist, carbachol, inhibited beta
      adrenergic (isoproterenol) stimulation of contractility (cell shortening) by 82%
      and increased cGMP levels by 49% within 6 min. Pretreatment of myocytes with
      soluble guanylyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one,
      ODQ) or NO synthase inhibitor (N(G)-monomethyl-L-arginine, L-NMMA) for 30 min
      blocked carbachol-induced increases in cGMP levels. However, neither ODQ nor L
      NMMA pretreatment had any effect on carbachol inhibition of isoproterenol-induced
      contractility. In addition, carbachol did not attenuate increases in myocyte
      contractility induced by forskolin (a direct activator of adenylyl cyclase) or 8
      (4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (a cell-permeable cAMP
      analog which activates cAMP-dependent protein kinase). Pretreatment of myocytes
      with G(i) protein inhibitor, pertussis toxin (PTX, 1 microg/ml), for 18-20 h
      abolished carbachol inhibition of isoproterenol-induced contractility.
      Furthermore, in ventricular myocytes isolated 3 days after in vivo treatment of
      rats with PTX (3 microg/100 g, i.p.), there was a complete loss of the negative
      inotropic effect of carbachol. These data indicate that pertussis toxin-sensitive
      G protein but not NO/cGMP pathway is required for muscarinic inhibition of beta
      adrenoceptor-mediated increases in contractility in adult rat ventricular
      myocytes.

PMID- 14646357
TI  - Determinants of arterial distensibility in patients with renal failure.
AB  - BACKGROUND: An increased stiffness of the arterial system is an adverse risk
      factor for the outcome in patients with renal disease. Few studies have focused
      on the determinants of an increased arterial stiffness in patients with renal
      failure. As the percentage of patients with renal failure secondary to vascular
      disease and/or diabetes mellitus is rapidly growing, and the underlying disease
      per se may also influence the arterial wall properties, it may also be of
      interest to study the arterial wall properties in relation to the etiology of
      kidney disease. METHODS: The distensibility coefficient (DC) of the common
      carotid artery was used as a marker of arterial stiffness. One hundred and
      seventeen patients were studied: 47 patients (aged 63 +/- 10 years) with renal
      failure secondary to vascular disease and/or diabetes mellitus and 70 patients
      (aged 57 +/- 13 years) with other diagnoses. The origin of the renal failure was
      retrieved from the patients' charts. RESULTS: Age, mean arterial pressure, and
      serum calcium level were each independent predictors of arterial stiffness (DC).
      The DC was significantly lower in the patients with vascular renal disease or
      diabetes mellitus [11.0 +/- 5.5 (1/MPa)] as compared with patients with
      renal/urological diseases [15.4 +/- 7.5 (1/MPa)]. Nevertheless, after correction
      for potentially confounding variables, the relation between cause of renal
      disease and DC lost significance in the overall group, but remained significant
      (p < 0.05) in the younger age groups (</=61 years; median age of the patient
      group). CONCLUSIONS: Age, mean arterial pressure, and serum calcium level were
      independent predictors of arterial stiffness in our patients with renal failure.
      Only in younger dialysis patients, the origin of renal failure was an independent
      predictor of arterial wall stiffness.

PMID- 14646358
TI  - Regulation of renal tubular bile acid transport in the early phase of an
      obstructive cholestasis in the rat.
AB  - BACKGROUND/AIMS: In obstructive liver diseases, urinary excretion of bile acids
      is markedly enhanced. The mechanism of this effect is not entirely clear. The aim
      of the present study was to assess the glomerular and tubular factors involved in
      the renal handling of bile acids during the early phase of an obstructive
      cholestasis induced by a 24-hour bile duct ligation in rats. METHODS: In addition
      to conventional clearance experiments, taurocholate transport was studied on
      proximal tubular cells freshly isolated from rat kidneys. The expression of the
      taurocholate transport protein was determined in these cells by immunoblotting.
      RESULTS: Glomerular filtration rate and arterial blood pressure were not
      significantly affected by the cholestasis induced. The (3)H-taurocholate and (3)H
      cholate clearances significantly increased whereas the fractional tubular
      reabsorption rates of these bile acids significantly fell. Probenecid did not
      affect the (3)H-taurocholate and (3)H-cholate clearances. By employing S0960, a
      specific inhibitor of the sodium-dependent bile salt transporter ASBT, it could
      be shown that this transporter mediates (3)H-taurocholate uptake into the
      proximal tubular cells. The bile duct ligation caused a significant decrease of
      the V(max) value of the taurocholate transporter indicating a downregulation of
      this transporter in cholestasis. The downregulation occurred without a change of
      the ASBT protein content of the proximal tubular cells. CONCLUSION: The results
      demonstrate that there is a functional adaptive downregulation of renal tubular
      bile acid transport enhancing renal clearance of bile acids during the early
      phase of an obstructive cholestasis.

PMID- 14646359
TI  - Influence of murine renal sexual dimorphism on amiloride-induced hyperkalemia.
AB  - The present study investigated the influence of androgens in potassium
      homeostasis both under normal conditions and when potassium balance was affected
      by the mild diuretic amiloride. Our results indicate the existence of a clear
      sexual dimorphism in renal and plasma potassium content in CD1 mice, adult males
      having a higher plasma potassium concentration than females or 40-day-old male
      mice (4.6 +/- 1.0 vs. 3.9 +/- 0.9 mEq/l). Plasma K(+) concentration was increased
      by testosterone treatment and decreased after orchiectomy, while the opposite
      occurred in the case of renal potassium concentration. Amiloride was well
      tolerated by CD1 female mice, but induced severe hyperkalemia in male mice, where
      it was also associated with a high rate of mortality. Testosterone treatment
      increased the toxicity of the diuretic in both CD1 female and male mice.
      Histopathological analysis of kidneys from CD1 male mice treated with amiloride
      revealed alterations at the proximal and distal tubule level. These results
      strongly suggest that androgens may produce adverse effects in renal function.

PMID- 14646360
TI  - Biology of the human podocyte.
AB  - The glomerulus is a complex physiological structure that, as well as maintaining
      a selective filtration barrier, participates in the control of renal blood flow
      and blood pressure. Recently there has been a surge of interest in the podocyte,
      as the main player in this functional unit, driven by key discoveries of genes
      mutated in hereditary conditions, that result in breakdown of barrier functions.
      This has been accompanied by the development of powerful new molecular, cellular
      and animal tools to enable study at a level of detail not previously possible.
      How this emerging information is shaping our understanding of glomerular biology,
      and ultimately our understanding of the pathophysiology of glomerular diseases,
      is outlined here.

PMID- 14646361
TI  - Effect of mycophenolate mofetil on glomerulosclerosis and renal oxidative stress
      in rats.
AB  - BACKGROUND/AIMS: Mycophenolate mofetil (MMF) is known to attenuate
      glomerulosclerosis in experimental models of renal failure. We investigated
      whether this is mediated by reduction of oxidative stress. METHODS: Effects of
      MMF on oxidative stress are studied in an experimental rat model (NA model)
      involving unilateral nephrectomy and two intravenous injections with adriamycin
      (2 mg/kg). Rats are sacrificed after 2 and 6 weeks. Glomerulosclerosis and
      tubulointerstitial lesions are demonstrated by histological techniques. Presence
      of macrophages/monocytes (ED1) and myofibroblasts (alpha-SMA) is demonstrated by
      immunohistochemistry. Oxidative stress is evaluated by enzymatic measurements
      (AOE), spectrofluorometry (TBARS), immunohistochemistry (MDA and HNE) and
      histology (ferric iron deposition). RESULTS: The NA model shows proteinuria,
      hypercholesterolemia, beginning glomerulosclerosis, tubulointerstitial sclerosis
      and tubular dilatation, glomerular, periglomerular and interstitial presence of
      alpha-SMA and increased presence of macrophages/monocytes after 6 weeks.
      Oxidative stress in renal cortex is apparent (increased cortex TBARS
      concentration, increased glomerular presence of MDA and HNE, decreased activity
      of antioxidant enzymes, ferric iron deposition in proximal tubules) after 6
      weeks. MMF administration results in a decrease of glomerulosclerosis,
      interstitial sclerosis, glomerular and periglomerular expression of alpha-SMA and
      the number of ED1-positive cells in tubulointerstitium and glomeruli. Proteinuria
      and cholesterolemia are not decreased. TBARS level, and activities of catalase,
      Mn and Cu/Zn superoxide dismutase as well as the presence of ferric iron in the
      proximal tubules are not changed by MMF treatment. Cortex activity of glutathione
      peroxidase returns to normal. CONCLUSION: MMF has a favorable effect on
      glomerular and interstitial fibrosis in the NA model of kidney disease, but not
      on proteinuria and cholesterolemia. Improvement of fibrosis cannot be explained
      by major changes in oxidative stress or antioxidant defense.

PMID- 14646362
TI  - Blocking VLA-4 prevents progression of experimental crescentic
      glomerulonephritis.
AB  - BACKGROUND/AIMS: Integrins are adhesion molecules of fundamental importance to
      the recruitment of leucocytes in inflammation. The alpha4beta1 integrin (VLA-4)
      is a leucocyte ligand for endothelial vascular cell adhesion molecule-1 (VCAM-1),
      fibronectin and osteopontin. We addressed the role of VLA-4 in mediating
      progressive renal injury in vivo using a blocking monoclonal antibody (mAb) in a
      rat model of crescentic glomerulonephritis. METHODS: WKY rats with nephrotoxic
      nephritis were given anti-VLA-4 or control mAb at 2.5 mg/kg by i.p. injection on
      alternate days. In separate experiments, antibodies were given from days 5-13,
      from days 13-21 or from days 14-28. RESULTS: Early treatment with anti-VLA-4 mAb
      from days 5-13 showed a significant effect on renal function, with a reduction in
      albuminuria (p < 0.01) and a higher creatinine clearance (p < 0.05). Delayed
      treatment from days 13-21 also showed a reduction in albuminuria (p < 0.05) and
      serum creatinine (p < 0.05). However, there was no significant effect on
      glomerular or interstitial scarring in these two experiments. In the late
      treatment study, in which anti-VLA-4 mAb was administered from days 14-28, serum
      creatinine was reduced (p < 0.05), creatinine clearance was improved (p < 0.05),
      and renal survival was significantly prolonged (p < 0.05). Interstitial scarring
      was significantly less in treated rats (p < 0.05). Glomerular macrophage and CD8+
      cell counts were higher in anti-VLA-4 mAb treated rats (p < 0.05), possibly
      reflecting greater glomerular scarring in control animals. CONCLUSION: Leucocyte
      VLA-4 mediates pro-inflammatory and pro-fibrotic effects within the kidney,
      independent of any role in recruitment of leucocytes into the kidney. Blocking
      VLA-4 is a promising therapeutic approach in human glomerulonephritis.

PMID- 14646363
TI  - Uremic toxins overload accelerates renal damage in a rat model of chronic renal
      failure.
AB  - Uremic toxins have been suggested to promote progression of chronic renal failure
      by damaging tubular cells. Previous in vitro studies have indicated that some
      uremic toxins induce oxidative stress and activate NF-kappaB to upregulate
      plasminogen activator inhibitor-1 in tubular cells. These mechanisms may promote
      tubulointerstitial fibrosis. The present study examined whether uremic toxins
      induce glomerular and tubulointerstitial damage in vivo. Two uremic toxins,
      hippuric acid (HA) or indoleacetic acid (IAA), were tested in two independent
      experiments (HA-treated rats vs. non-HA-treated controls, IAA-treated rats vs.
      non-IAA-treated controls). The uremic toxins were administered to subtotally
      nephrectomized rats. Renal functions were measured periodically and glomerular
      sclerosis and interstitial fibrosis were examined at the end of the experimental
      period (18 and 24 weeks, respectively, after subtotal nephrectomy for HA and IAA
      treatments). Glomerular filtration rate (inulin clearance) at the end of the
      study period was significantly lower in uremic toxin-treated rats than in control
      rats (HA-treated rats: 0.090 +/- 0.004 ml/min/100 g body weight vs. non-HA
      treated controls: 0.125 +/- 0.013, IAA-treated rats: 0.068 +/- 0.006 versus non
      IAA-treated controls: 0.100 +/- 0.013; both p < 0.05). Beta-N-acetyl
      glucoseamidase excretion was significantly higher in uremic toxin-treated rats
      than in control rats (HA-treated: 0.55 +/- 0.05 U/day vs. control: 0.39 +/- 0.04
      at week 18, IAA-treated: 0.35 +/- 0.02 vs. control: 0.26 +/- 0.07 at week 16;
      both p < 0.05). Glomerular sclerosis index was significantly higher in uremic
      toxin-treated rats than in control rats (HA-treated: 0.85 +/- 0.16 versus
      control: 0.48 +/- 0.10, IAA-treated: 1.13 +/- 0.25 vs. control: 0.57 +/- 0.10;
      both p < 0.05). Significant enlargement of interstitial fibrosis was observed in
      indoleacetic acid-treated rats. These results indicate that overload of uremic
      toxins accelerates the loss of kidney function, glomerular sclerosis and
      tubulointerstitial injury in a rat model of chronic renal failure. The present
      study suggests the potential benefit of early intervention to remove various
      uremic toxins in delaying the onset of end-stage renal failure in patients with
      progressive renal disease.

PMID- 14646364
TI  - AT1 receptor expression in glomeruli from NO-deficient rats.
AB  - Chronic inhibition of nitric oxide synthase promotes renin-dependent hypertension
      and renal injury. The present study examines how renal angiotensin II receptors
      are expressed in this model. N(G)-nitro-L-arginine methyl ester (L-NAME) was
      given orally to rats for 1 month and was associated or not with captopril during
      the 4 last days of the administration. 125I-[Sar1, Ile8]-Ang II binding, AT1)mRNA
      and cytosolic calcium were studied in isolated glomeruli from L-NAME and control
      rats and in cultured mesangial cells from normal rats. Renal injury was marked in
      rats receiving L-NAME. Type I angiotensin II (AT1) receptor number and mRNA
      expression were decreased (p < 0.05) in glomeruli isolated from L-NAME-treated
      rats compared with controls, unless they received captopril in combination. The
      low level of AT1 receptor expression was associated with an attenuated rise of
      cytosolic calcium in response to angiotensin II. Angiotensin-converting enzyme
      activity in glomeruli and angiotensin II concentration in renal cortex were
      increased (p < 0.05) in rats receiving L-NAME alone, whereas aminopeptidase A
      activity was not modified. To better discriminate between the direct and indirect
      effects of nitric oxide deficiency, rat mesangial cells were exposed or not for
      24 h to S-nitroso-N-acetyl penicillamine, a nitric oxide donor. Angiotensin II
      binding, AT1 mRNA expression and calcium response to angiotensin II were
      decreased in presence of the nitric oxide donor (p < 0.01). These results suggest
      that the decrease of AT1 receptor expression after 1 month of L-NAME treatment
      does not depend on a direct effect of nitric oxide deficiency but results from
      the high local angiotensin II concentration due to the stimulated angiotensin
      converting enzyme activity. They also show that the renin-angiotensin dependence
      of this model of hypertension does not result from the overexpression of AT1
      receptors.

PMID- 14646365
TI  - Halting chronic allograft nephropathy--do we already have the drugs?

PMID- 14646366
TI  - Urine--a mirror of the (glomerular) soul?

PMID- 14646367
TI  - Compositional lipoprotein changes and low-density lipoprotein susceptibility to
      oxidation in chronic renal failure patients with heavy proteinuria.
AB  - BACKGROUND: There are limited data regarding qualitative lipoprotein
      abnormalities in undialysed uremic patients without proteinuria. In this report,
      we focused on lipoprotein changes observed in uremic patients with proteinuria as
      well as on the susceptibility of low-density lipoprotein (LDL) of these patients
      to oxidative modification in vitro. METHODS: 20 patients with chronic renal
      failure [serum creatinine >1.6 mg/dl (141.4 micromol/l)], but not yet on renal
      replacement therapy, and with heavy proteinuria (>2 g/24 h), and 18 age- and sex
      matched healthy individuals participated in the study. In both patients and
      controls, venous blood was collected for determination of serum lipid and
      lipoprotein levels, lipoprotein subfraction profile and chemical composition, as
      well as the susceptibility of LDL subfractions to oxidation. RESULTS: Patients
      exhibited a more atherogenic lipid profile compared with the control population.
      Furthermore, the total very LDL + intermediate-density lipoprotein mass was
      increased in patients compared with controls, while this subfraction was
      triglyceride enriched in uremic patients. The total LDL concentration was
      significantly higher in patients compared with controls due mainly to an increase
      in the mass of all lipoprotein subfractions. It is noteworthy that the mass of
      small dense LDL was significantly elevated in patients compared with controls
      (135 +/- 12 vs. 115 +/- 11 mg/dl, p = 0.01), an increase which was more
      pronounced in hypertriglyceridemic patients. Furthermore, the subfraction high
      density lipoprotein-2 mass was significantly lower in uremic patients compared
      with controls. Finally, no significant differences in the lag time, the rate of
      oxidation and the relative electrophoretic mobility values in each LDL
      subfraction between the two groups were observed. CONCLUSION: We conclude that
      uremic patients with heavy proteinuria exhibit compositional lipoprotein changes
      that are less marked than those observed in nonuremic patients with nephrotic
      syndrome. However, there is no evidence that circulating LDL isolated from these
      patients is more susceptible to oxidation in vitro than lipoprotein isolated from
      age- and gender-matched controls.

PMID- 14646368
TI  - Renoprotective effects of losartan in renal transplant recipients. Results of a
      retrospective study.
AB  - BACKGROUND/AIMS: Chronic allograft nephropathy is the main cause of late graft
      loss and nonimmunological factors, including hypertension and proteinuria, the
      principal etiological factors. In this context, blockage of the renin-angiotensin
      system could be helpful. The aim of the present study was to review the
      renoprotective efficacy of losartan in a large group of renal transplant patients
      undergoing long-term follow-up. METHODS: A retrospective analysis of 276 renal
      transplant patients treated with losartan was performed. The indication for
      losartan was arterial hypertension in 163 patients, proteinuria in 37 patients
      and hypertension plus proteinuria in the remaining 76 patients. Clinical and
      biochemical parameters before starting losartan treatment (-6 months, -3 months
      and at baseline) and 3, 6, 9, 12, 18 and 24 months after the introduction of
      losartan were analyzed. RESULTS: Arterial hypertension significantly decreased
      after the introduction of losartan (p = 0.000). Serum creatinine was
      significantly decreased by losartan therapy, and changes in the serum creatinine
      slope (1/sCr) before and after losartan were statistically significant.
      Proteinuria markedly decreased after the introduction of losartan. Clinical and
      biochemical tolerance of losartan was excellent in most patients and only 9 out
      of the 276 patients (3%) treated with losartan discontinued the drug because of
      an adverse event. During follow-up, only 3 patients required substitutive
      treatment with dialysis due to progressive deterioration of renal function in the
      context of chronic allograft nephropathy. CONCLUSION: Losartan demonstrated high
      efficacy as a renoprotective agent in renal transplant patients and could be
      useful in the treatment and prevention of chronic allograft nephropathy.

PMID- 14646369
TI  - Urinary sediment podocalyxin in children with glomerular diseases.
AB  - BACKGROUND: In an immunofluorescence study using antibody to podocalyxin, we
      reported that urinary excretion of podocytes reflected podocyte injury in
      glomeruli. However, this method has some problems, since it is basically urine
      cytology. To overcome problems with this test, we measured whole podocalyxin
      content in urine sediment by enzyme-linked immunosorbent assay (ELISA). METHODS:
      Urinary sediment podocalyxin (u-sed-PCX) content of the first morning urine was
      quantified by ELISA after solubilization by detergent. We measured urine samples
      from children with various glomerular diseases and from healthy volunteers as
      controls. The glomerular diseases were classified into two categories: group I
      (inflammatory glomerular, 5 diseases) and group II (non-inflammatory glomerular,
      3 diseases). RESULTS: (1) The level of u-sed-PCX was significantly higher in the
      urine from patients with glomerular diseases (groups I and II, median
      (interquartile range (IQR)): 2 (0.6-18.5), n = 111) compared with controls (0 (0
      0.4), n = 135), and the level of u-sed-PCX in group I diseases (3.4 (0.6-27.2), n
      = 90) was significantly higher than those in group II diseases (0.9 (0.1-2.5), n
      = 21). (2) The presence of PCX in urine sediment was confirmed by Western blot
      analysis. (3) The degree of proteinuria was significantly correlated with the
      level of u-sed-PCX in group I (r(s) = 0.539, p < 0.001), but not in group II. (4)
      In group I, the level of u-sed-PCX was significantly higher in the acute phase
      than in the chronic phase (p < 0.01). (5) Comparison of histological findings of
      renal biopsies with u-sed-PCX showed a significant correlation in acute
      extracapillary lesions (p < 0.05). (6) Persistent high level of u-sed-PCX
      paralleled good histological progression in renal biopsies. CONCLUSION:
      Quantification of urinary sediment podocalyxin by ELISA is a reliable and useful
      laboratory marker for the estimation of the severity of active glomerular injury
      and a urinary index of acute extracapillary changes.

PMID- 14646370
TI  - Matrix metalloproteinase-9 expression in renal biopsies of patients with HIV
      associated nephropathy.
AB  - BACKGROUND/AIMS: The normal architecture and function of the kidney are
      maintained by a critical turnover of the extracellular matrix (ECM). Although
      increased synthesis of ECM leads to progression of renal failure, the role of
      degradation of ECM by metalloproteinases in progressive nephropathies is unclear.
      Recently, in an animal model of membranous glomerulonephritis (Heymann
      nephritis), visceral epithelial cell (VEC) injury has been found to rapidly
      increase matrix metalloproteinase-9 (MMP-9) synthesis by these cells during the
      period of maximal proteinuria. Because injury to glomerular VECs may be an
      important initiating factor in the pathogenesis of focal segmental
      glomerulosclerosis (FSGS), especially in HIV-associated nephropathy (HIVAN), we
      determined the expression of MMP-9 and its inhibitors in renal biopsies of
      patients with HIVAN. METHODS: RNA was isolated from cortical renal tissue of 6
      patients with HIVAN. Only those biopsies which displayed characteristic findings
      of HIVAN including collapsing FSGS, cystic dilatation of the tubules, and
      proliferation of VECs were used. As controls, we obtained renal cortical tissue
      from normal areas of kidneys removed due to malignancies. MMP-9, tissue inhibitor
      of metalloproteinase (TIMP)-1 and TIMP-2 mRNA expressions were determined using
      real-time quantitative reverse transcription-polymerase chain reaction. In all 6
      patients with HIVAN, MMP-9 and TIMP-1 were overexpressed. We localized MMP-9
      protein to the glomeruli with immunohistochemical detection. CONCLUSION: MMP-9 is
      overexpressed in the glomeruli of patients with HIVAN and may be involved in the
      pathogenesis of the disease.

PMID- 14646371
TI  - Aging increases neuronal nitric oxide release and superoxide anion generation in
      mesenteric arteries from spontaneously hypertensive rats.
AB  - We hypothesized that neuronal NO release as well as its bioavailability and
      vasomotor response could be affected when aging and hypertension are present
      simultaneously. The neuronal nitric oxide (NO) release, its metabolism and
      vasomotor response induced by electrical field stimulation was analyzed in
      isolated segments of endothelium-denuded mesenteric arteries from young and old
      spontaneously hypertensive rats (SHR). The nitric oxide synthase (NOS) inhibitor
      N(G)-nitro-arginine-methyl ester (L-NAME) and NOS inhibitor 7-nitroindazole both
      strengthened electrical field stimulation-elicited contractions more in arteries
      from young than aged SHR rats. Superoxide dismutase (SOD) potentiated the L-NAME
      effect in segments from old rats, whereas catalase decreased the contractions
      induced by electrical field stimulation and noradrenaline but did not modify the
      L-NAME effect. In noradrenaline-precontracted segments, sodium nitroprusside
      induced a similar relaxation in arteries from both experimental groups. This
      relaxation was increased by SOD in old SHR. 8Br cGMP induced greater relaxation
      in segments from old than from young SHR. Electrical field stimulation induced a
      tritium release in arteries preincubated with [(3)H]-noradrenaline, that was
      similar in both young and old SHR rats. Electrical field stimulation induced
      NO(2)(-) formation, which was greater in segments from old than young SHR rats.
      Basal cGMP levels and those stimulated with sodium nitroprusside were similar in
      segments from both groups. Superoxide anion production was greater from old than
      young SHR rats. Peroxynitrite production induced by electrical field stimulation
      was only detected in segments from old SHR. The results obtained in mesenteric
      arteries from old SHR showed increased neuronal NO release and superoxide anion
      production with respect to those observed in arteries from young SHR rats. This
      induced decreased NO bioavailability through peroxynitrite formation. The final
      effect is to decrease the involvement of neuronal NO in electrical field
      stimulation-induced vasomotor response in arteries from old SHR rats.

PMID- 14646372
TI  - Augmented contractile response of vascular smooth muscle in a diabetic mouse
      model.
AB  - The vasomotor properties of isolated aortae and mesenteric arteries of insulin
      resistant ob/ob and 57CBL/6J mice were compared in organ bath studies. Vessels
      from ob/ob mice were more sensitive to phenylephrine. Pretreatment with L-NAME
      caused similar leftward shifts of the phenylephrine concentration response curves
      in diabetic and non-diabetic vessels. The ob/ob aortae contracted in response to
      phenylephrine with roughly twice the force while they were not stiffer than
      control aortae. L-NAME caused a greater percentage increase in maximal force in
      the control than in the ob/ob tissue. Denudation potentiated force in the control
      aortae, but not in the ob/ob aortae. Endothelium-dependent relaxation in the
      ob/ob aortae and mesenteric arteries was impaired as manifested by a decreased
      sensitivity and maximal relaxation to acetylcholine, while the aortic basal eNOS
      mRNA levels did not differ between the two strains. In addition, ob/ob aortae
      were less sensitive to the nitric oxide donor sodium nitroprusside. Inhibition of
      endogenous prostaglandin synthesis with indomethacin (10 microM) partly
      normalized the contractile response of the ob/ob aortae and enhanced their
      endothelium-dependent relaxation. Neither blockade of endothelin-1 receptors
      (bosentan, 10 microM) nor PKC inhibition (calphostin, 1 microM) affected the
      contractile response to phenylephrine in the mouse aortae of either strain. In
      conclusion, vascular dysfunction in the aorta and mesenteric artery of ob/ob mice
      are due to increased smooth muscle contractility and impaired dilation but not to
      changes in elasticity of the vascular wall. Endothelium-produced prostaglandins
      contribute to the increased vasoconstriction.

PMID- 14646373
TI  - High dose allergen stimulation of T cells from house dust mite-allergic subjects
      induces expansion of IFN-gamma+ T Cells, apoptosis of CD4+IL-4+ T cells and T
      cell anergy.
AB  - BACKGROUND: During clinically effective allergen-specific immunotherapy a shift
      in cytokine dominance from IL-4, IL-5 predominant to IFN-gamma predominant has
      been observed. As antigen concentration influences Th cell priming, this study
      aimed to determine the effect of different allergen concentrations on human house
      dust mite (HDM)-specific T cell production of IL-4 and IFN-gamma, proliferation
      and apoptosis. METHODS: HDM-allergic donor PBMC were cultured for 14 days with
      different concentrations of HDM extract (1, 10 and 100 microg/ml). T cell
      intracellular IL-4 and IFN-gamma, division (CFSE labelling) and apoptosis (active
      caspase-3 staining) were analysed by flow cytometry. Proliferation was assessed
      by (3)H-thymidine incorporation. RESULTS: Increased CD4+IFN-gamma+ and CD8+IFN
      gamma+ T cell numbers were observed in high allergen concentration cultures
      compared with low concentration cultures whereas there were no differences in
      CD4+IL-4+ and CD8+IL-4+ T cell numbers. CFSE cell labelling revealed that high
      allergen concentration favours the expansion of IFN-gamma-producing CD4+ T cells.
      The proportion of apoptotic cells increased with allergen concentration and there
      was preferential apoptosis of CD4+IL-4+ T cells. HDM-induced proliferation was
      decreased in high allergen concentration cultures; this was reversible by IL-2
      consistent with anergy. CONCLUSION: These results show that T cell division and
      apoptosis contribute to the cytokine skewing to predominant IFN-gamma production
      by T cells observed at high allergen concentration. Thus the use of
      hypoallergenic T cell reactive preparations which can be given safely at higher
      doses than natural extracts may enhance efficacy of allergen-specific
      immunotherapy.

PMID- 14646374
TI  - Bronchial hyperreactivity and spirometric impairment in patients with perennial
      allergic rhinitis.
AB  - BACKGROUND: Allergic disorders are characterized by a systemic involvement of the
      immune response. There is a clear link between allergic rhinitis and asthma.
      Bronchial hyperreactivity (BHR) may be present in rhinitics. Smaller airways may
      also be impaired in mild asthma. This study aimed at evaluating a group of
      subjects suffering from perennial allergic rhinitis alone to investigate the
      presence of BHR and spirometric impairment. METHODS: One hundred rhinitics
      sensitized only to perennial allergens were evaluated. Spirometry and
      methacholine bronchial challenge were performed. RESULTS: Five rhinitics showed
      reduced values of forced expiratory volume/1 s (FEV(1)) without symptoms of
      asthma. Forty-eight rhinitics had reduced forced expiratory flow at 25 and 75% of
      pulmonary volume (FEF(25-75)) values. Seventy-two patients showed a positive
      methacholine challenge. In this group, reduced values of FVC (p < 0.05), FEV(1)
      (p < 0.05), and FEF(25-75) (p < 0.01) were demonstrated in comparison with BHR
      negative rhinitics. There was a relationship between the degree of BHR and FEV(1)
      values (p < 0.05) and FEF(25-75) values (p < 0.01). CONCLUSIONS: This study
      evidences that an impairment of spirometric parameters may be observed in
      patients with perennial allergic rhinitis alone. A high percentage of these
      patients have BHR. Thus, new management strategies should be employed in
      rhinitics.

PMID- 14646375
TI  - Estrogen altered oral tolerance induction in type II collagen-induced murine
      arthritis.
AB  - BACKGROUND: Estrogen plays an important modulatory role in the immune system, and
      is concerned with the pathophysiology of autoimmune diseases such as rheumatoid
      arthritis (RA), although the mechanism has not yet been clarified. Oral
      tolerance, a form of specific peripheral tolerance, which is recognized as a new
      therapeutic strategy, is related to the function of gut-associated lymphoid
      tissue. METHODS: In this study, using collagen-induced arthritis as an animal
      model of RA, the effects of 17beta-estradiol (E2) on oral tolerance induction
      were investigated. For induction of oral tolerance, mice were fed 60 microg type
      II collagen (CII) for 10 consecutive days prior to each CII immunization. Mice in
      the E2 treatment groups were injected with 5 microg (low dose) or 500 microg
      (high dose) E2 three times during the induction of oral tolerance. RESULTS: Oral
      tolerance induction suppressed the occurrence of arthritis, the proliferative
      response of splenocytes to CII and the specific DTH response. However, E2
      treatment abrogated the suppression, which might be connected with a change in
      function of Peyer's patch (PP) lymphocytes. CONCLUSION: These results suggest
      that oral tolerance induction might be affected by estrogen treatment through
      alteration of intestinal immune responses.

PMID- 14646376
TI  - Allergy-like asthma and rhinitis. A cross-sectional survey of a respiratory
      cohort and a diagnostic approach using the autologous serum skin test.
AB  - BACKGROUND: Chronic idiopathic urticaria is considered an allergy-like skin
      disorder, and in some cases an auto-reactivity caused by mast cell degranulating
      factors has been demonstrated. A positive reaction to the autologous serum skin
      test (ASST), reflecting the presence of factors capable to degranulate the mast
      cells, is regarded as a reliable in vivo diagnostic test in chronic urticaria
      patients. About one out of three patients complaining for rhinitis or asthma does
      not show sensitization to any allergenic source. No data are available on the
      application of ASST to respiratory patients. METHODS: A cohort of respiratory
      patients, aged 1 to 80 years, complaining about suspected respiratory symptoms
      was screened using a panel of inhalant allergens by means of SPT and IgE. Current
      and past information on skin and respiratory symptoms were recorded for each
      patient. Patients were divided in 'allergy' and 'allergy-like' whether or not
      they react to at least one allergenic source. Age and gender distribution were
      analyzed. A control group fulfilling criteria for chronic idiopathic urticaria
      (CIU) was selected as well. The ASST was applied to the control CIU group, to the
      allergy-like and allergy subsets, and to a group of 58 healthy adult subjects.
      RESULTS: Allergy and allergy-like patients were differently distributed in
      relation to age and gender. Allergy-like children were prevalent before age six,
      whereas the prevalence of allergics steadily increased with age representing the
      large majority of patients in late childhood. The ratio of allergy/allergy-like
      subjects continues to increase in adult males, whereas adult females represent
      the large majority of the adult patients mainly within the allergy-like subset.
      Fifty-eight percent of CIU control patients reacted to the ASST. Among allergy
      like patients ASST was positive in 47% of the adults (male 26%, female 54%), and
      in 84% of the children (no gender differences). The percentage of reactive
      subjects increased in the adult allergy-like subset if a CIU was associated
      (65%). Eighty-six percent of the pediatric patients and 61% of the adults having
      an allergy respiratory disease associated with an allergy-like condition had a
      positive ASST reactivity. Pure allergy patients reacted in 73% and 40% of the
      cases in the children and adults subgroups, respectively. Forty-five percent of
      healthy controls reacted to the ASST as well, and statistically significant
      gender differences were still recorded. CONCLUSIONS: An ASST reactivity is
      reported for the first time in allergy-like respiratory patients. A higher
      prevalence of reactive subjects has been recorded in all the pediatric subsets
      without gender differences, whereas female reactivity is prevalent among adults.
      The ASST reactivity seems to parallel the patient distribution within the entire
      respiratory cohort. Further studies are needed to demonstrate that the serum
      factors causing the ASST reactivity in respiratory patients are the same as for
      CIU affected subjects. In the light of recent in vitro findings, the ASST
      reactivity of healthy subjects could lead to a new interpretation of the
      autologous serum reactivity.

PMID- 14646377
TI  - Repeated aerosol allergen exposure suppresses inflammation in B-cell-deficient
      mice with established allergic asthma.
AB  - BACKGROUND: Repeated allergen administration is a well-established therapeutic
      strategy for desensitizing patients with allergic disease. Similarly, repeated
      inhalation of antigen by mice with established allergen-induced asthma suppresses
      allergic inflammation. The mechanisms underlying antigen-dependent suppression of
      allergic immune responses remain unknown. In previous studies, we found that
      repeated aerosol antigen challenges in sensitized mice reduced eosinophils while
      increasing plasma cells and antibody in the lungs. We sought to test whether
      plasma cells and antibody played a role in suppression of allergic disease.
      METHODS: We primed wild-type and B-cell-deficient (microMT) mice with 25 microg
      ovalbumin (OVA) precipitated in alum on days 0 and 5, nebulized weekly with 1%
      OVA, 1 h, twice daily, for up to 6 weeks, and assessed lung inflammation, mucus
      hypersecretion, and IgE/IgG1. RESULTS: Kinetic studies revealed that initial
      aerosol exposure induced high numbers of eosinophils, lymphocytes, and
      macrophages within lung infiltrates and increased mucus production in wild-type
      mice. After 3-4 weeks of antigen exposure, eosinophils diminished while
      lymphocytes, plasma cells, and macrophages and mucus hypersecretion increased.
      However, by 6 weeks, lung inflammation and mucus hypersecretion were dramatically
      reduced. In contrast, repeated aerosol challenges maintained OVA-specific IgG1
      and IgE production. Repeated aerosol antigen challenges in microMT mice resulted
      in reduced lung inflammation and mucus hypersecretion and the development of
      smooth muscle hypertrophy of the pulmonary microvasculature. CONCLUSIONS: B cells
      and antibody do not appear to play a role in antigen-dependent suppression of
      allergic responses in mice.

PMID- 14646378
TI  - Injection immunotherapy with different airborne allergens did not prevent de novo
      sensitization to ragweed and birch pollen north of Milan.
AB  - BACKGROUND: Previous studies suggest that allergen-specific immunotherapy (SIT)
      with a single allergen may prevent sensitization to other airborne allergens.
      OBJECTIVE: To assess the effectiveness of injection SIT in preventing
      sensitization to birch and ragweed pollen north of Milan, a geographical area
      that was recently colonized by these two airborne allergens. METHODS: 691 adult
      patients monosensitized to grass (n = 342), pellitory (n = 76), ragweed (n = 66),
      birch (n = 112), and house dust mite (n = 95) were studied. 284 (41%) of them
      received injection SIT as part of routine outpatient care; the remaining 407
      (59%) not submitted to SIT, served as controls. All patients underwent follow-up
      visits after no less than 2 years in order to detect possible new sensitization
      to birch and/or ragweed. RESULTS: 227 (33%) patients became sensitized to birch
      and/or ragweed pollen during the follow-up period. Surprisingly, the prevalence
      of new sensitizations was significantly higher among subjects receiving SIT
      (132/284; 46%) than among those not receiving SIT (95/407; 23%; p < 0.001). 27
      subjects developed new sensitization to birch and/or ragweed pollen while
      undergoing SIT. These findings were consistent in all subgroups with different
      airborne allergies. CONCLUSION: In this study, injection SIT did not exert any
      preventive effect against denovosensitization to the two novel airborne
      allergens, birch and ragweed pollen, in adult monosensitized patients.

PMID- 14646379
TI  - HIV/AIDS in Central Africa: pathogenesis, immunological and medical issues.
AB  - The estimated worldwide prevalence of human immunodeficiency virus (HIV)
      infections topped 52.5 million in June 2003, a mere 20 years after the
      aetiological agent was shown to be a sexually transmissible virus with a
      predilection for CD4+ T lymphocytes. More than 22 million people have died of the
      acquired immunodeficiency syndrome (AIDS) and the condition has in one generation
      become the most devastating and persistent epidemics in recorded history. More
      than two thirds of the world total of HIV-infected people live in Sub-Saharan
      Africa. In Central and Southern Africa at least 20% of the adult population is
      infected. As these adults die, they leave increasing numbers of orphans. Life
      expectancy at birth declined by 10 years per decade since the late 1980s to 50
      years in the late 1990s, and in Botswana it is estimated to be as low as 33 years
      by 2010. The epidemic is increasing unabated and prospects for a curative or
      protective vaccine remain remote. The impact on HIV in Africa has been so
      profound that it influences political, economic, agriculture/food security,
      social, education, defence, science and health considerations. The medical and in
      particular immunology communities in Central Africa have the invidious challenge
      of on the one hand diagnosing the condition, monitoring its impact and
      contributing to treatment and management efforts. The science and clinical
      practice of immunology is challenged to find answers to the epidemic, perhaps
      including a vaccine. In this review we address the peculiarities of the HIV
      epidemic in Africa, its epidemiology and immunopathogenesis. We address the
      effect of the epidemic on individual patients, in their homes, workplaces and the
      knock-on effects on families and friends of the infected. Respective specialists
      discuss special groups (women, children) that are predominantly seen in Africa.
      We also discuss the impact of the epidemic on the clinical practice of medicine
      in general and challenges faced in the introduction of antiretroviral medicines.
      We also discuss options available for the diagnosis, treatment and monitoring of
      HIV-infected patients in this region.

PMID- 14646380
TI  - Viral RNA and p24 antigen as markers of HIV disease and antiretroviral treatment
      success.
AB  - HIV-1 RNA has become the standard for monitoring antiretroviral therapies. Dogma
      predicts, however, that a viral protein like p24 should be at least as good a
      marker of HIV disease activity, provided that it is measured with sufficient
      sensitivity and accuracy. Simple modifications including use of a more efficient
      virus lysis buffer, heat-mediated destruction of antibodies interfering with
      antigen detection, and tyramide signal amplification for increased sensitivity
      have highly improved the HIV-1 p24 antigen assay. The p24 antigen assay is
      inferior to RT-PCR in detecting viral particles, but the presence of extraviral
      p24 antigen in most samples makes largely up for this. p24 antigen testing is
      similarly sensitive and specific in diagnosing pediatric HIV infection, in
      predicting CD4+ T cell decline and clinical progression at early and late stage
      of infection, and suitable for antiretroviral treatment monitoring in both adults
      and children. Notably, p24 antigen was measurable even in patients with stably
      suppressed viremia, and its concentrations were correlated negatively with the
      concentrations of CD4+ T cells and positively with the concentrations of
      activated CD8+ T cell subsets. p24 antigen is an excellent marker of HIV
      expression and disease activity and can be used in the same fields of application
      as HIV RNA is used. The test is validated for subtype B, but requires further
      studies for non-B subtypes.

PMID- 14646381
TI  - Asthma as a paradigm for autoimmune disease.
AB  - Allergy and autoimmunity result from dysregulation of the immune system. Until
      recently, it was generally accepted that the mechanisms that govern these disease
      processes are quite disparate; however, new discoveries suggest possible common
      pathogenetic effector pathways. This review illustrates the concomitant
      presentation of these conditions and the potential relationship or common
      mechanisms in some cases, by looking at the key elements that regulate the immune
      response in both asthma and autoimmune conditions: mast cells, antibodies, T
      cells, cytokines, and genetic determinants. The parallel appearance of asthma and
      autoimmune conditions in the same patients may reveal that such aberrations of
      the immune system have a common pathophysiologic mechanism. Mast cells, which
      play a key role in asthma, and the wealth of inflammatory mediators they express,
      make it likely that they have profound effects on many autoimmune processes.
      Activation of protein kinases by inflammatory cytokines and environmental
      stresses may contribute to both allergic and autoimmune diseases. The presence of
      autoantibodies in some allergic diseases suggests an autoimmune basis for these
      conditions. Because of the central role T cells play in immune reactivity, the T
      cell receptor loci have long been considered important candidates for a common
      disease susceptibility within the immune system such as asthma, atopy, and
      autoimmunity. Immunomodulation is the key to successful treatment of asthma and
      autoimmune conditions.

PMID- 14646382
TI  - Sensitization profiles of Malaysian and Singaporean subjects to allergens from
      Dermatophagoides pteronyssinus and Blomia tropicalis.
AB  - BACKGROUND: The house dust mites Dermatophagoides pteronyssinus (Der p) and
      Blomia tropicalis (Blo t) are the most common house dust mite species in
      Southeast Asia. To date, there have only been a few studies on the sensitization
      profile of the general populations in Southeast Asia to house dust mites. The aim
      of this study was to determine the profiles of Der p and Blo t sensitization
      among Singaporean and Malaysian subjects. METHODS: Enzyme-linked immunosorbent
      assay was used to detect specific IgE to Der p and Blo t mite crude extracts as
      well as purified Der p 1, Der p 2 and Blo t 5 allergens. Sera used were from 229
      Singaporean subjects (124 with rhinitis, 105 without rhinitis) and 143 Malaysian
      subjects (94 adults and 49 children with asthma). RESULTS: The sensitization
      profile of rhinitis subjects to the dust mite allergens used in this study was as
      follows: Blo t extract positive: 91/124 (73%); Blo t 5 positive: 62/124 (50%);
      Der p extract positive: 61/124 (49%); Der p 1 positive: 53/124 (43%); Der p 2
      positive: 45/124 (36%). The nonrhinitis subjects' sensitization profile was as
      follows: Blo t extract positive: 60/105 (57%); Blo t 5 positive: 24/105 (23%);
      Der p extract positive: 38/105 (36%); Der p 1 positive: 14/105 (13%); Der p 2
      positive: 17/105 (16%). The study of Malaysian asthmatic adults showed that 39%
      of them were sensitized to Der p 1, 32% to Der p 2 and 37% to Blo t 5. Among the
      asthmatic children, sensitization to Blo t 5, Der p 1 and Der p 2 was 90, 57 and
      39%, respectively. CONCLUSION: This study clearly revealed that dual
      sensitization to B. tropicalis and D. pteronyssinus is common in the general
      populations of Singapore and Malaysia. Sensitization to Blo t 5 is more prevalent
      than to Der p 1 and Der p 2.

PMID- 14646383
TI  - Mast cell degranulation induced by lectins: effect on neutrophil recruitment.
AB  - The mammalian lectin macrophage-derived neutrophil chemotactic factor (MNCF) and
      the plant lectin KM+ were characterized for their ability to activate and
      degranulate mast cells. The association between mast cell activation and the
      induction of neutrophil migration was also investigated. Incubation of rat
      peritoneal mast cells with these lectins resulted in degranulation and mediator
      release. By confocal microscopy, both lectins were evenly distributed on the cell
      surface. MNCF activated RBL-2H3 mast cells only if the cells had been sensitized
      with IgE. KM+ was able to activate either unsensitized or IgE sensitized RBL-2H3
      cells. In microplate assays MNCF, but not KM+, bound to rat IgE. In rats that
      were depleted of mast cells, neutrophil recruitment by MNCF and KM+ were
      significantly reduced indicating that mast cell activation provides an
      amplification loop for the neutrophil recruitment induced by these lectins. The
      present study supports the concept that mammalian lectins play a fundamental role
      in innate immunity.

PMID- 14646384
TI  - Azelastine inhibits secretion of IL-6, TNF-alpha and IL-8 as well as NF-kappaB
      activation and intracellular calcium ion levels in normal human mast cells.
AB  - BACKGROUND: Mast cells are involved in allergic inflammation by secreting
      histamine, proteases and several cytokines, including interleukin (IL)-6, tumor
      necrosis factor-alpha (TNF-alpha) and IL-8. Certain histamine-1 receptor
      antagonists, such as azelastine present in the ophthalmic solution Optivar, have
      been reported to inhibit histamine and tryptase secretion, but its effect on
      inflammatory cytokine release from normal human umbilical cord blood-derived
      cultured mast cells (hCBMC) are not well known. METHODS: We investigated the
      effect of azelastine on the secretion of IL-6, TNF-alpha and IL-8 from hCBMC, as
      well as its possible mechanism of action. hCBMC sensitized with IgE were
      pretreated for 5 min with azelastine at 0.01, 0.1, 1, 3, 6, 12, 24, or 60 microM
      of Optivar, before stimulation with anti-IgE for 6 h. Optivar vehicle without
      azelastine was used as control. Cytokines were measured by ELISA, intracellular
      calcium levels by calcium indicators confocal, and nuclear factor-kappaB (NF
      kappaB) by electromobility shift assay. RESULTS: Stimulation with anti-IgE led to
      substantial secretion of IL-6, TNF-alpha and IL-8. Preincubation for 5 min
      resulted in almost maximal inhibition with 6 microM azelastine for TNF-alpha
      (80%), with 24 microM for IL-6 (83%) and 60 microM for IL-8 (99%); the vehicle
      solution at the same concentrations as Optivar had no effect. Stimulation with
      anti-IgE increased intracellular Ca2+ level and induced NF-kappaB expression in
      hCBMC, which was inhibited by 24 microM azelastine. CONCLUSION: Azelastine
      inhibited hCBMC secretion of IL-6, TNF-alpha and IL-8, possibly by inhibiting
      intracellular Ca2+ ions and NF-kappaB activation. Azelastine may, therefore, be
      helpful in treating allergic inflammation.

PMID- 14646385
TI  - Bisphenol A promotes IL-4 production by Th2 cells.
AB  - BACKGROUND: It has been proposed that estrogen plays an important role in
      modulating the Th1/Th2 cytokine balance. From this viewpoint, chemicals with
      estrogenic responses were expected to possess similar immunoregulatory roles
      which have not been defined to date. To address this, we studied the effects of
      one of the estrogenic chemicals, bisphenol A (BPA), on the in vitro production of
      Th1 and Th2 cytokines. METHODS: Mesenteric lymph node cells from Trichinella
      spiralis (Ts)-infected mice were incubated with serialfold dilutions of BPA under
      stimulation with Ts antigen. The Th2 cytokine production in the supernatant was
      determined by ELISA. The Th2 cytokine production by mesenteric lymph node cells
      from Ts-infected mice inoculated orally with BPA was compared with that of
      uninoculated mice infected with Ts. RESULTS: The antigen-stimulated interleukin
      (IL)-4 production by Th2-dominant mesenteric lymph node cells from Ts-infected
      mice increased significantly by addition of 3 microM of BPA. The IL-5 production
      was not affected. The production of IL-4, but not that of IL-5, by splenocytes of
      Th2-skewed Leishmania major-infected BALB/c mice increased at concentrations of 3
      and 10 microM of BPA. However, the interferon gamma production was not affected
      by BPA in Th1-skewed L. major-infected C57BL/6 mice. The production of IL-4 and
      IL-10, but not that of IL-13, markedly increased in Ts-infected mice inoculated
      orally with BPA. CONCLUSIONS: We demonstrated that the IL-4 production was
      increased both in vitro and in vivo by treatment with BPA. This suggests that BPA
      might cause allergic diseases by stimulating the IL-4 production by Th2 cells.

PMID- 14646386
TI  - Low-dose oral tolerance due to antigen in the diet suppresses differentially the
      cholera toxin-adjuvantized IgE, IgA and IgG response.
AB  - BACKGROUND: Cholera toxin (CT) is used as a mucosal adjuvant amongst other
      applications for studying food allergy because oral administration of antigen
      with CT induces an antigen-specific type 2 response, including IgE and IgA
      production. Previously established oral tolerance due to antigen in the diet may
      radically impact on the CT-adjuvantized immune response. The present study served
      to evaluate the effect of previously established low-dose oral tolerance on the
      CT-adjuvantized immune response towards a food antigen. METHODS: Mice fed a diet
      containing microgram levels of the soy protein Kunitz soy-trypsin inhibitor
      (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized
      with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were
      monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production
      were determined. RESULTS: The anti-KSTI IgE and IgA responses in the F0 mice were
      substantially suppressed, while the IgG1 and IgG2a responses were not suppressed
      after five oral immunizations. The response suppression tended to decline with
      increasing numbers of immunizations suggesting that the suppression could be
      overcome by multiple immunizations. However, cell proliferation and IL-6
      production were clearly suppressed even after five immunizations. CONCLUSIONS:
      Priorly established low-dose oral tolerance considerably suppressed the CT
      adjuvantized KSTI-specific IgE, IgA and cellular immune response but only weakly
      and transiently the IgG response. The results revealed that low-dose oral
      tolerance includes the mucosal IgA response and that CT, albeit mediating an
      antigen-specific response, does not fully abrogate previously established oral
      tolerance.

PMID- 14646387
TI  - Safety of subcutaneous specific immunotherapy with pollen allergen extracts for
      respiratory allergy.
AB  - BACKGROUND: Specific immunotherapy (SIT) is a well-documented treatment for
      respiratory allergy. However, the major risk of SIT is the development of
      systemic anaphylactic reactions. OBJECTIVES: To evaluate the safety of SIT given
      by subcutaneous route for 3 years to patients with seasonal allergic rhinitis
      (AR) with or without asthma. METHODS: A prospective open-label study of
      immunotherapy (Chenopodium album, Bermuda grass, or both) in 181 consecutive
      patients with AR with or without asthma. After an initial dose-escalation phase,
      a maintenance dose of 0.5 ml of 100,000 PNU/ml was administered monthly for 3
      years. The occurrence and severity of systemic reaction (SR) and local reaction
      was recorded and graded according to the WHO position paper. RESULTS: Of 181
      patients enrolled, 57 (31%) did not complete the study (53 due to poor compliance
      and 4 due to systemic side effects). All 4 patients who developed SR had asthma
      and all the SR occurred during the dose- escalation phase. Three patients had
      moderate SR (grade 2), while 1 patient had severe reaction (grade 3). Three of
      the SR occurred within the first 20 min after injection and 1 SR occurred 2 h
      after injection. None of the reactions were life threatening and were managed
      easily. Total rhinitis symptom score decreased from 11.8 at baseline to 7.46 at
      the end of treatment (p<0.001). The size of the skin prick test reaction to the
      main sensitising allergen was reduced from 7.48 +/- 2.26 mm at baseline to 5.60
      +/- 2.18 mm at the end of treatment, p<001. CONCLUSION: If a strict protocol is
      used, SIT is safe in AR patients with or without mild asthma and may result in
      significant subjective and objective improvement.

PMID- 14646388
TI  - A study comparing the inhibitory effects of single and repeated oral doses of
      ebastine and fexofenadine against histamine-induced skin reactivity.
AB  - OBJECTIVE: The aim of this double-blind, randomized, crossover, placebo
      controlled clinical trial was to compare the inhibition of the histamine-induced
      skin reaction induced by ebastine 20 mg with respect to that induced by
      fexofenadine 120 mg or placebo. METHODS: Eighteen volunteers (10 males, 8
      females) received the three treatments once daily for 5 days, with a mean 7-day
      washout period between treatments. Intradermal tests, using 0.05 ml from a
      solution containing 100 microg/ml of histamine, were performed at baseline and at
      1, 1.5, 2, 3, 10 and 24 h after a single dose and repeated 5-day dose, and in
      addition after 34, 48, 58 and 72 h after repeated 5-day dose. RESULTS: After 24 h
      of acute administration, ebastine 20 mg was significantly more effective than
      fexofenadine 120 mg in reducing the wheal and flare induced by histamine
      challenge (p<0.001). Although fexofenadine 120 mg had the shortest onset of
      action (1.5 vs. 3 h in ebastine 20 mg), the duration of its antihistamine effect
      was the shortest (24 vs. 58 h in ebastine 20 mg) and wheal reduction after 24 h
      was not significantly different from placebo. The overall effect after single and
      repeated 5-day dose, expressed as the AUC of reduction of wheal and flare area
      (%/h), showed the following order of magnitude: ebastine 20 mg>fexofenadine 120
      mg>placebo. No significant differences in the incidence of adverse events were
      found between the three treatments. CONCLUSIONS: The present results clearly show
      a superior and long-acting effect of ebastine 20 mg compared with fexofenadine
      120 mg on the skin response to histamine 24 h after dosing.

PMID- 14646389
TI  - Increase in serum levels of autoantibodies after attack of seasonal allergic
      rhinitis in patients with Graves' disease.
AB  - BACKGROUND: The prevalence of allergic disease is increasing worldwide, but its
      influence on the clinical course of autoimmune diseases is unknown. OBJECTIVE:
      The purpose of this study was to assess the effect of seasonal allergic rhinitis
      on the clinical course of Graves' disease, which has been considered a Th2
      dominant autoimmune disease. METHODS: Ten patients with Graves' disease, who were
      considered to be in a state of remission or near remission, were serially
      examined for 18 months starting from August. Five of them had seasonal allergic
      rhinitis due to Japanese cedar pollen, and the remaining patients had no such
      allergic disorders. Peripheral eosinophil counts, serum concentrations of cedar
      pollen-specific IgE, anti-TSH-receptor antibody, anti-thyroid-peroxidase antibody
      and antithyroglobulin antibody were assessed at 2- to 4-month intervals. Serum
      thyroid hormones and TSH levels were also measured to evaluate disease activity.
      RESULTS: All patients with pollinosis had attacks of allergic rhinitis caused by
      cedar pollen in early March. Subsequently, peripheral eosinophil counts, pollen
      specific IgE activity and serum levels of anti-thyroid-peroxidase and
      antithyroglobulin autoantibodies markedly increased. Serum levels of anti-TSH
      receptor antibody increased in 3 patients in association with an increase in
      serum thyroid hormones but were always negative in 2 patients. The control
      patients without pollinosis showed no consistent change of these parameters.
      CONCLUSIONS: Seasonal allergic rhinitis aggravated the clinical course of Graves'
      disease and induced an increase in serum antithyroid autoantibody concentrations
      as well as an increase in pollen-specific IgE concentration. These data suggest
      that environmental antigens induce not only local allergic reactions, but also
      stimulate thyroid immune reactions toward Th2 proliferation, and finally
      aggravate Th2-dependent autoimmune thyroid disease.

PMID- 14646390
TI  - Thyrotropin-releasing hormone stimulation test in patients with pituitary
      pathology.
AB  - OBJECTIVES: To evaluate the value of the thyrotropin-releasing hormone (TRH)
      stimulation test in the diagnostic work-up of the thyroid function in patients
      with pituitary pathology. METHODS: To compare the thyrotropin (TSH) response and
      the absolute and fold changes after TRH administration in 35 patients with
      pituitary pathology and 26 normal subjects. RESULTS: Nine of the patients and 2
      of the normal subjects had a pathological response. No difference in the
      thyrotropic response to TRH was found either for the actual values, or for the
      absolute or fold changes of TSH between the groups. CONCLUSION: The role of the
      TRH test in the evaluation of thyroid function in patients with pituitary
      pathology is modest. The best variables for evaluation of the presence of central
      hypothyroidism are still a free thyroxine estimate combined with an
      inappropriately low TSH.

PMID- 14646391
TI  - A novel mutation in the D-box of the androgen receptor gene (S597R) in two
      unrelated individuals Is associated with both normal phenotype and severe PAIS.
AB  - BACKGROUND: An absent or dysfunctional androgen receptor (AR) in 46,XY
      individuals is the most common cause of various degrees of undermasculinization.
      Therefore, we routinely perform sequencing of the AR gene in all cases with
      suspected androgen insensitivity. METHODS: In a newborn 46,XY male diagnosed with
      partial androgen insensitivity syndrome and a phenotypically normal man, who in
      childhood had bilateral cryptorchidism, the AR was directly sequenced. Seven
      additional men with cryptorchidism in infancy were chosen as controls. RESULTS:
      An AR variant (S597R) was identified in both males. Treatment of the newborn with
      1% dihydrotestosterone ointment locally, resulted in normal penile size for age.
      Sequencing of the region in 7 other men with cryptorchidism in infancy did not
      reveal any additional deviation from the normal reference sequence. CONCLUSION:
      The same mutation at this codon can cause significantly different phenotypes as
      shown by the variation in masculinization of these individuals, with 1 severely
      affected child and 1 normally developed man. However, the S597R mutation does not
      seem to be a common cause of undescended testes in boys. Despite the S597R
      mutation and severe undermasculinization, as seen in the baby, normal male
      phenotype for age could be achieved with treatment.

PMID- 14646392
TI  - Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide
      and amiloride in an adult patient.
AB  - AIM: The effects of treatment with hydrochlorothiazide (HCTZ) combined with
      amiloride were elucidated and compared to HCTZ treatment alone and combined with
      acemetacin or triamterene in a Japanese adult patient with congenital nephrogenic
      diabetes insipidus. METHODS: The study was divided into seven periods: (1) HCTZ
      and acemetacin; (2) control period; (3) HCTZ; (4) a second control period; (5)
      HCTZ and amiloride; (6) a third control period, and (7) HCTZ and triamterene.
      Fluid intake, urine volume, urinary Na, K, creatinine, and osmolality and serum
      Na, K, Cl, CO2, and osmolality were measured, and free water clearance and
      proximal and distal tubular Na reabsorption rates were calculated. RESULTS:
      Without drug administration, the urine volume was about 8,000 ml/day. The urine
      volume was reduced to about 6,000 ml/day with HCTZ. A further urine volume
      reduction to about 5,000 ml/day was obtained with the second drug administration,
      and the effects were similar among the three regimens. Serum and urinary
      osmolality and free water clearance were also similar among the three
      combinations, whereas the urinary potassium excretion was the least, and the
      serum potassium concentration was the highest with HCTZ plus amiloride. Besides,
      no alkalosis was observed only with this combination. CONCLUSION: HCTZ plus
      amiloride may be superior to HCTZ plus acemetacin and HCTZ plus triamterene in
      preventing hyperkaliuria, hypokalemia, and metabolic alkalosis.

PMID- 14646393
TI  - Endocrine disorders of sodium regulation. Role of adrenal steroids in genetic
      defects causing sodium loss or sodium retention.
AB  - Salt and water homoeostasis is tightly regulated by a variety of control
      mechanisms with the adrenal steroid hormone aldosterone playing a central role.
      Defects or disturbances in these systems lead to either salt loss, which is life
      threatening in the neonatal period, or sodium retention causing hypertension.
      Rapid and accurate diagnosis is required to avoid severe complications. During
      the last few years molecular genetic advances have been identified as the basic
      genetic defects for a number of clinical syndromes. This knowledge has
      considerably increased our understanding of the basic pathways involved in sodium
      and water homoeostasis and of the pathophysiology of these syndromes,
      particularly the hypertension. In this review we have summarized the biochemical,
      physiological and genetic basis for clinical syndromes presenting with salt loss
      and failure to thrive as well as the rare but important genetic syndromes causing
      sodium retention and hypertension. Early diagnosis and identification will help
      to prevent severe complications, but it has to be emphasized that the complicated
      cascade of aldosterone action is still relatively poorly understood. Further
      syndromes may exist which once identified will help to better understand the
      basic physiology of aldosterone action.

PMID- 14646394
TI  - Cortisol responses to the insulin hypoglycaemia test in children.
AB  - AIM: To determine the timing of the peak cortisol response to the insulin
      hypoglycaemia (IH) test in children and to establish paediatric reference data.
      METHODS: We retrospectively reviewed all IH tests in a tertiary paediatric
      endocrine referral centre over a 6-year period. Inclusion criteria were age <16
      years and adequate hypoglycaemia (glucose < or =2.0 mmol/l). Patients with an
      impaired hypothalamic-pituitary-adrenal axis or receiving glucocorticoid
      medication were excluded. Fifty-four subjects (35 males) met the criteria. Blood
      samples were collected at -30, 0, 20, 30, 60, 90, 120, and 150 min in relation to
      insulin bolus injection (0.15 U/kg) at 0 min. Glucose, cortisol, and growth
      hormone (GH) were measured in all samples. RESULTS: Peak cortisol and GH
      responses occurred by 90 min in all subjects. Peak cortisol was inversely
      correlated with age (rs -0.65, p<0.0001). The median (5th centile) peak cortisol
      value was 689 nmol/l (547 nmol/l) in children younger than 10 years as compared
      with 555 nmol/l (468 nmol/l) in those older than 10 years (p<0.0001). Peak
      cortisol was not related to peak GH (rs -0.20, p=0.15). CONCLUSIONS: Blood
      sampling in the IH test may be curtailed 90 min after injection. The peak
      cortisol response to IH is age related.

PMID- 14646395
TI  - Three children with triple A syndrome due to a mutation (R478X) in the AAAS gene.
AB  - OBJECTIVE: To investigate the phenotype and genotype of 3 unrelated children with
      triple A syndrome from southern Turkey. METHODS: The coding sequence of the AAAS
      gene was sequenced including exon-intron boundaries. Haplotype analysis using
      markers from AAAS region was performed in order to assess potential founder
      effects. RESULTS: In all 3 patients, the identical nonsense mutation (R478X) in
      exon 16 of the AAAS gene was identified. The patients who may be distantly
      related appeared phenotypically similar with the classical triad of the triple A
      syndrome (adrenal insufficiency, alacrima and achalasia) with dermatological
      manifestations while lacking neurological features except for mild mental
      retardation. CONCLUSION: The R478X mutation tends to result in a rather severe
      phenotype although genotype-phenotype relationships cannot be drawn due to the
      small number of patients.

PMID- 14646396
TI  - 1,25-(OH)2-16ene-23yne-D3 reduces secondary hyperparathyroidism in uremic rats
      with little calcemic effect.
AB  - OBJECTIVES: To compare the effects of vitamin D analogs versus calcitriol on
      serum levels of Ca, P and parathyroid hormone (PTH). A compound better than
      calcitriol should increase the Ca x P product less than calcitriol for an
      equivalent decrease in PTH levels. METHODS: Biological activity of 4 vitamin D
      analogs, 1,25-(OH)(2)-16ene- D(3) (RO(1)), 1,25-(OH)(2)-16ene-23yne-D(3) (RO(2)),
      1,25-(OH)(2)-26,27-hexafluoro-16ene-23yne-D(3) (RO(3)) and 1,25-(OH)(2)-16ene
      23yne-26,27-hexafluoro-19nor-D(3) (RO(4)) was tested vs. calcitriol in
      parathyroidectomized rats. In a second set of experiments, the effects of RO(2),
      RO(4) and calcitriol were studied in 5/6 nephrectomized rats with secondary
      hyperparathyroidism. RESULTS: In parathyroidectomized rats, all analogs (250
      pmol/day) led calcemia to rise after 7 days. In uremic rats, all treatments
      reduced PTH levels. RO(4) revealed toxicity. RO(2) was as effective as calcitriol
      in suppressing PTH in a dose dependent manner. Mean plasma ionized calcium did
      not change from baseline to day 14 and day 28 on RO(2) (250 or 500 pmol/day)
      whereas it increased significantly on RO(2) (1,000 pmol/day) and calcitriol (125
      or 250 pmol/day). Increasing the dose of calcitriol led Ca x P to rise more
      dramatically than increasing the dose of RO(2), which appears to have a wider
      therapeutic window than calcitriol. CONCLUSION: 1,25-(OH)(2)-16ene-23yne-D(3)
      (RO(2)) may represent a novel candidate for the treatment of renal osteodystrophy
      in humans.

PMID- 14646398
TI  - Catch-up growth in females born short for gestational age reduces the risk of
      giving birth to short-for-gestational-age infants.
AB  - OBJECTIVES: The aim of the present study was to study the effect of catch-up
      growth on the offspring's length at birth among females born short for
      gestational age. METHODS: Data of 1,363 females born short for gestational age (<
      2 standard deviation scores) were obtained from the Swedish Birth Register. The
      females were included in the register both as babies and mothers. The effect of
      catch-up growth on the offspring's birth length was studied. RESULTS: Short adult
      stature was associated with a threefold increase in the risk of giving birth to a
      short infant [OR 3.08 (CI 1.73-5.50)] and smoking increased the risk in a dose
      dependent manner. Overweight was associated with a reduced risk [OR 0.46 (CI 0.22
      0.96)] of giving birth to a short infant. CONCLUSION: Catch-up growth to normal
      adult stature among women born short for gestational age is associated with a
      reduced risk of giving birth to a short-for-gestational-age infant.

PMID- 14646397
TI  - Differential effect of fetal, neonatal and treatment variables on
      neurodevelopment in infants with congenital hypothyroidism.
AB  - OBJECTIVES: To identify the influence of fetal, neonatal and treatment variables
      on neurodevelopment in children with congenital hypothyroidism. METHODS: A
      multiple regression analysis was performed in the neurodevelopmental scores of 26
      children with CH who were assessed at 3, 6, 12 and 18 months for postural
      control, fine eye-hand coordination and language. The independent variables were:
      duration of fetal hypothyroidism, initial biochemical severity, days at starting
      treatment, initial dose, and efficiency of treatment. RESULTS: Postural control
      was predicted by duration of fetal hypothyroidism and language by the biochemical
      severity of the disease at birth. Fine eye-hand coordination was not predicted by
      any variable. CONCLUSION: This pattern of influences suggests that fetal and
      neonatal hypothyroidism have different effects on brain maturation sites during
      the first 2 years of life and that some subtle neurocognitive deficits are
      probably unavoidable.

PMID- 14646399
TI  - Altered kinetics of pituitary response to gonadotropin-releasing hormone in women
      with variant luteinizing hormone: correlation with ovulatory disorders.
AB  - OBJECTIVE: The LH response of pituitary gland to gonadotropin-releasing hormone
      (GnRH) stimulation is not well defined in patients with mutant beta-subunit
      (Trp(8) to Arg(8) and Ile(15) to Thr(15)). Here we compared the relative
      activities and dynamics of LH secretion in patients with wild-type and variant LH
      following injection of GnRH. METHODS: A GnRH stimulation test was performed in 33
      patients with ovulatory disorders (patient group) and 29 women with normal
      ovulatory cycles (control group) heterozygous for the variant LHbeta allele.
      Blood samples were obtained up to 120 min after GnRH injection. Serum LH response
      was determined by comparing the results of LH immunoassays using a monoclonal
      antibody that recognizes wild-type LH only with those of another assay using a
      polyclonal antibody that recognizes equally both variant and wild-type LH (total
      LH). The ratio of variant LH to total LH (LH ratio) was used to determine the
      serum LH status. RESULTS: The LH ratio in the control group showed the peak 15
      min after GnRH injection, while that in the patient group showed the peaks 30-60
      min after injection. The LH ratio in the patient group at 120 min after injection
      was significantly lower than that in the control group. The percent increases in
      LH ratio in both groups showed the peak 15 min after injection. The patient group
      had significantly lower changes of LH ratio at 15, 60, 90 and 120 min after GnRH
      injection compared with that in the control group. CONCLUSION: Differences in
      circulatory kinetics of the two types of LH may explain the differences in LH
      function between patients with ovulatory disorders and women with normal
      ovulatory cycles.

PMID- 14646400
TI  - Extreme short stature after intrauterine growth retardation: factors associated
      with lack of catch-up growth.
AB  - The factors associated with lack of catch-up growth after intrauterine growth
      retardation (IUGR) are unknown. OBJECTIVE: To identify these factors by analyzing
      the clinical features and growth hormone (GH)-insulin-like growth factor I (IGF
      I) axis. METHODS: 95 patients with height <-3 SD after IUGR were assigned to
      group 1 without (n = 50) or group 2 with (n = 45) malformations. Twenty-one in
      group 1 and 19 in group 2 were treated with GH. RESULTS: They were seen at 5.3 +/
      0.5 and 4 +/- 0.5 year (p = 0.02) with heights at -3.4 +/- 0.1 and -3.9 +/- 0.2
      SD (p = 0.03). Group 1 differed from group 2 in having a lower frequency of
      consanguinity (2 vs. 28.9%, p < 0.001), and higher frequencies of target heights
      (26.5 vs. 6.7%, p = 0.02) and mothers' heights (34.7 vs. 8.9%, p < 0.01) <-2 SD,
      multiparity (26 vs. 8.9%, p < 0.05), prematurity (36 vs. 15.5%, p < 0.05) and
      cesarean section birth (42 vs. 17.8%, p = 0.01). The GH-IGF-I axis data and the
      height increases after 3 years of GH treatment (1.6 +/- 0.2 in group 1 and 1.1 +/
      0.3 SD in group 2) were similar. CONCLUSION: The short height of the parents,
      particularly of the mother, is associated with factors limiting the catch-up
      growth after IUGR of children without malformations, while the high frequency of
      consanguinity in those with malformations suggests that transmitted fetal factors
      affect organogenesis or development.

PMID- 14646401
TI  - The C105fs114X is the prevalent thyrotropin beta-subunit gene mutation in
      Argentinean patients with congenital central hypothyroidism.
AB  - BACKGROUND: Congenital isolated thyrotropin (TSH) deficiency is an unusual
      condition characterized by low levels of thyroid hormones and TSH, usually
      presenting early typical signs of severe hypothyroidism. Five different beta-TSH
      mutations have been described so far. While 4 of them affect only consanguineous
      families, a frameshift mutation in exon 3 (C105fs114X) has been found also in
      nonconsanguineous families. OBJECTIVE: The aim of the present study was to
      characterize beta-TSH mutations in Argentinean patients with congenital central
      hypothyroidism (CCH) and to emphasize the importance of early biochemical and
      molecular diagnosis of this disorder. PATIENTS AND METHODS: We investigated 8
      Argentinean children (3 boys, 5 girls) from 7 unrelated families with CCH based
      upon low levels of T(4) and T(3), and low basal and stimulated TSH levels.
      Mutation characterizations for the beta-TSH gene were performed by PCR
      amplification followed by sequence and restriction enzyme analysis with SNABI in
      the patients, 9 parents and in 100 newborn children. RESULTS: All patients
      presented the same homozygous mutation in exon 3 of the beta-TSH gene
      (C105fs114X), the 9 studied parents were heterozygous for the same mutation and 1
      carrier was found in the 100 studied newborns. CONCLUSION: Our findings show that
      the C105fs114X mutation is prevalent in our population and may constitute a hot
      spot at codon 105 in the beta-TSH gene. Since this mutation is easily
      demonstrable by a SNABI digestion in DNA amplified from dried blood spots, its
      investigation would be indicated in patients in our milieu with clinical and
      biochemical features of CCH, allowing early L-thyroxine (LT(4)) replacement and
      genetic counseling of the family.

PMID- 14646402
TI  - Observational study on the efficacy of tibolone in counteracting early carotid
      atherosclerotic lesions in postmenopausal women.
AB  - OBJECTIVE: To study whether tibolone affects lipid profile and diffused intima
      media thickness (IMT) of the common carotid arteries (CCA) in postmenopausal
      women (PMW). METHODS: Twenty-two PMW and 20 premenopausal women participated in
      the study. The PMW were randomly divided into 11 women who did not receive any
      treatment and 11 women who received tibolone (2.5 mg once a day). RESULTS: After
      6 months the treated women had lipoprotein(a) (Lpa), total-cholesterol (total-C),
      and LDL-cholesterol (LDL-C) levels lower than before, while in the non-treated
      women Lpa was increased. The IMT of CCA was unmodified in the treated women,
      whereas it increased in non-treated women. CONCLUSIONS: This preliminary study
      suggests that a 6-month tibolone treatment could counteract the increase of the
      IMT of CCA observed in untreated PMW.

PMID- 14646403
TI  - Effects of oxytocin outside pregnancy.
AB  - For a long time, oxytocin was regarded as a pregnancy hormone released by the
      hypophysis to stimulate labour and milk ejection. In the present survey, data
      have been collected from the literature to show the spectrum of the hitherto
      known functions of oxytocin outside pregnancy. It is now known that oxytocin
      receptors can occur almost ubiquitously in the organism, that oxytocin is also
      formed outside of the brain and that oxytocin has functions in a number of
      organs. In the first part of the survey, stimuli that contribute to an increase
      in oxytocin release are compiled. In the second part, details are given on the
      individual oxytocin targets. Although the majority of findings are based on the
      results of animal experiments, there are already a number of studies that
      indicate similar effects of oxytocin in humans. According to the current state of
      knowledge, oxytocin appears to be involved in functions in the following organs:
      male and non-pregnant female reproductive tract, pancreas, cardiovascular system,
      kidney, brain and breast. There are indications that oxytocin may also have
      actions in other organs. There continues to be a considerable need for research
      into oxytocin in order to better understand the physiological and
      pathophysiological actions and to be able to derive possible therapeutic uses.
      Further light on the spectrum of functions of oxytocin may be cast by the
      possibility of the use of oxytocin antagonists.

PMID- 14646404
TI  - Extremely short stature: influence of each parent's height on clinical-biological
      features.
AB  - Idiopathic extremely short stature probably has several causes. OBJECTIVE: To
      evaluate the influence of each parent's height on clinical-biological features.
      METHODS: 57 patients without intrauterine growth retardation seen at 7.9 +/- 0.4
      years for height < or = -3 SD were classified according to the difference between
      their target height and actual height: < 2 SD in familial short stature (FSS, n =
      28) and >2 SD in non-FSS (n = 29). RESULTS: Height decreased from -0.5 +/- 0.1 SD
      at birth to -2 +/- 0.2 SD at 1 year and -2.7 +/- 0.1 SD at 3 years, but the
      changes in the two groups were similar. FSS children were shorter than non-FSS
      children both at birth (p = 0.03) and as adults after growth hormone (GH)
      treatment (p < 0.05), but their plasma insulin-like growth factor I
      concentrations and GH peaks were similar. The FSS children fathers' heights were
      more frequently below -2 SD (64%) than the mothers' heights (35%) and were
      correlated with height at first evaluation (p < 0.05). For the whole population,
      the mothers' heights were correlated with birth weight (p < 0.05) and with height
      at first evaluation (p < 0.03). CONCLUSION: This study confirms the influence of
      the mother's height on birth weight and shows how of the father's height
      influences idiopathic extremely short stature.

PMID- 14646405
TI  - Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in
      combined pituitary hormone deficiency patients with abnormal pituitary MR
      imaging.
AB  - BACKGROUND/AIMS: Many genes encoding pituitary transcription factors involved in
      the formation of the pituitary gland are identified. Different mutations in these
      genes have been reported in patients with familial combined pituitary hormone
      deficiency (CPHD). This study was undertaken to analyze PIT1, PROP1, LHX3, and
      HESX1 in 12 CPHD patients with abnormal pituitary magnetic resonance imaging
      (MRI). Since embryonic development of the pituitary requires the coordinated
      expression of specific transcription factors, we postulated the presence of
      mutations in PIT1, PROP1, LHX3, and HESX1 genes. METHODS: Anterior pituitary
      function was evaluated. Each gene was PCR amplified exon by exon, and
      subsequently sequenced. RESULTS: In all cases, MRI examination showed abnormal
      pituitary gland development featuring ectopic neurohypophysis, hypoplastic
      anterior lobe, empty sella, and septo-optic dysplasia. Endocrinologically, all
      patients revealed multiple pituitary hormone deficiency including growth hormone,
      thyroid stimulating hormone, luteinizing hormone, follicular stimulating hormone
      and adrenocorticotropin. They were all sporadic cases without a positive family
      history. None of disease-causing specific mutations were identified in PIT1,
      PROP1, LHX3, and HESX1 genes of 12 sporadic CPHD patients with abnormal pituitary
      imaging. However, 2 novel polymorphisms were found in PROP1 gene: IVS1+3 A-->G
      and 27 T-->C (Ala9Ala) in exon 1. Their allele frequencies in patients and normal
      controls were not statistically different. Overall, allele frequencies of these
      polymorphisms were as follows: for the IVS1+3 A-->G polymorphism, the allele
      frequency of A was 54%, and 46% for G, with 58% of an A/G heterozygosity. For the
      27 T-->C (Ala9Ala) polymorphism, the allele frequency of T was 46%, and 54% for
      G, with 42% of a T/C heterozygosity. CONCLUSIONS: Mutations of PIT1, PROP1, LHX3,
      and HESX1 genes are very rare in sporadic CPHD patients with abnormal pituitary
      MRI.

PMID- 14646406
TI  - Annual changes in bone mineral content and body composition during growth.
AB  - OBJECTIVES: To compute the annual changes in total bone mineral content (BMCt),
      lean tissue mass and fat mass (LTM and FM) during growth. METHODS: Whole body DXA
      data were used to calculate the annual changes of the parameter P (P = BMCt, LTM
      or FM), as a percentage, as DeltaP% = 100 x (P(i+1) - P(i)) / P(i); with P(i) and
      P(i+1) the values for P at age i and age (i+1). Smoothed curves were then
      obtained from DeltaP% values plotted against age. RESULTS: Changes in FM were
      different in males and females. A peak velocity was marked for the three tissues
      at age 6.5 in boys, and at age 6.5-7.5 in girls; a pubertal peak spurt appeared
      at age 12 in girls and between age 13 and 14 in boys. This latter peak was
      followed by an exponential decrease, and no significant changes were found for
      the three components after age 20 in girls and age 21-22 in boys. CONCLUSION:
      Changes in tissue accretion during growth are easy to follow when expressed in
      percentages. Fat changes, especially, should be around 17% in girls and 15% in
      boys at the age of puberty.

PMID- 14646407
TI  - Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in
      growth-hormone-treated and untreated patients.
AB  - OBJECTIVE: To determine whether postprandial lipids, coagulation factors and
      homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD)
      adolescents. METHODS: Fifteen GHD adolescents on GH replacement were studied. Ten
      untreated GHD adolescents and 15 healthy subjects served as controls. Fasting
      lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1,
      homocysteine, folate and vitamin B12 levels were measured. Cholesterol and
      triglycerides were measured 4 h after a high fat meal. RESULTS: Fasting and
      postprandial triglycerides and homocysteine levels of untreated GHD patients were
      increased compared to those of GH-treated GHD subjects and healthy controls;
      fibrinogen concentrations were elevated in both treated and untreated
      adolescents. CONCLUSIONS: GHD adolescents present an abnormal fasting and
      postprandial lipid profile. In addition, the increased fibrinogen and
      homocysteine levels are suggestive of the accumulation of cardiovascular risk
      factors early on in life.

PMID- 14646408
TI  - Metabolic effects of growth hormone therapy in an Alstrom syndrome patient.
AB  - AIM: To investigate the metabolic effects of recombinant human growth hormone
      (rhGH) in an Alstrom syndrome patient with growth hormone deficiency. METHODS: A
      15-year-old Alstrom syndrome boy with growth hormone deficiency received rhGH
      therapy for 1 year. Biochemical parameters, including hepatic enzyme levels,
      lipid profiles, and insulin sensitivity, were measured. Body composition analysis
      and computed tomography scans of the liver were performed. RESULTS: After 1 year
      of rhGH treatment, body fat mass, fat infiltration in the liver, and serum lipid
      profiles had all decreased. Insulin sensitivity and acanthosis nigricans
      improved. CONCLUSION: rhGH therapy might have beneficial effects on body
      composition, liver fat content, lipid profiles, and insulin resistance in Alstrom
      syndrome patients, with improvement of the glucose homeostasis.

PMID- 14646409
TI  - 46,XY phenotypic male with focal segmental glomerulosclerosis caused by the WT1
      splice site mutation.
AB  - OBJECTIVE: Frasier syndrome is characterized by progressive glomerulopathy due to
      nonspecific focal and segmental glomerulosclerosis (FSGS), 46,XY sex reversal and
      the development of gonadoblastoma from dysgenetic gonads. Donor splice site
      heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) cause this
      disease. We investigated whether WT1 mutations showed clinical heterogeneity.
      PATIENTS AND METHODS: A 6-year-old phenotypic boy was diagnosed as having FSGS.
      His karyotype was 46,XY. Gonadotropin-releasing hormone and human chorionic
      gonadotropin stimulation tests revealed normal luteinizing hormone, follicle
      stimulating hormone and testosterone responses. The other patient was a 7-year
      old 46,XY female with FSGS. Prophylactic gonadectomy was performed and
      gonadoblastoma was found. By polymerase chain reaction and direct sequencing, WT1
      was analyzed in these patients. RESULTS AND CONCLUSION: Both patients had IVS9 +
      5G-->A in intron 9 of the WT1. Our study indicates a normal 46,XY phenotypic male
      patient with FSGS. The phenotypic variations of the WT1 splice site mutations are
      further expanded.

PMID- 14646410
TI  - Which stem cells should be used for transplantation?
AB  - In view of the ever-increasing demand for human stem cells for transplantation,
      we initiated in vitro and in vivo studies of human fetal bone marrow
      stem/progenitor cells derived from lost pregnancies at 16-20 weeks. Utilizing non
      human primates as models, we demonstrated that fetal tissue has distinctive
      biological and therapeutic properties that are optimal for transplantation.
      Subsequently, we tested and compared the phenotypic and functional
      characteristics of fetal bone marrow (FBM), adult bone marrow (ABM), and cord
      blood (CB) and peripheral blood (PB) sources of the most primitive
      stem/progenitor cells. A striking ontogenic difference in the proportion of CD34+
      cells in FBM, ABM, PB and CB was observed (24.6 vs. 2.1 vs. 0.5 vs. 2%). The
      clonogenic potential, as measured by the CFU-c assay, was also higher in FBM when
      compared with ABM, PB and CB (202.5 vs. 73.5 vs. 40.8 vs. 65.5 colonies/10(5
      )cells). Moreover, there was a significant decrease in proliferative
      responsiveness in the mixed lymphocyte reaction (MLR) assay of FBM and CB as
      compared to ABM and PB. The cytokinetic profiles of the cells from the four
      sources were also analyzed. This study revealed that both FBM and ABM had a
      higher proportion of S-phase (21.7 and 11.5%, respectively), compared to PB and
      CB cells (1.2 and 2.8%, respectively). FBM and ABM also showed a higher
      proportion of cells in the G(2)-M phase (6.4 and 2.6%, respectively) compared
      with PB and CB (1.7 and 1.2%, respectively). These data show that FBM has the
      highest number of proliferating cells. We have also investigated the ontogenic
      differences in stromal cells derived from FBM, ABM and CB, with a special focus
      on the expression of selected cytokines, such as CSF, GM-CSF, G-CSF, M-CSF, IL-3,
      IL-6, IL-10 and IL-11. FBM showed the highest levels of expression of CSF, IL-6
      and IL-11 when compared to the other sources. These cytokines may have an
      important role in engraftment and homing of stem cells. The levels of expression
      of the other cytokines were similar in all sources of stromal cells, with the
      exception of G-CSF, which was not detected in CB. Moreover, the number of
      colonies FBM and ABM cells was higher when inoculated with fetal stromal cells.
      These results suggested an important regulatory role of cytokines in ontogeny of
      hematopoiesis. In summary, the foregoing observations indicate that each source
      of hematopoietic and stromal cells has different intrinsic properties, closely
      correlated with ontogenetic age, which is a vital determinant for phenotypic
      characteristics, lineage commitments, immunogenicity as well as proliferative
      potentials. Our data clearly indicate that FBM is the best source of stem cells
      for engraftment and therapeutic reconstitution due to its very high proliferative
      capacity, low immunogenicity and highest number of primitive stem/progenitor
      cells. It should also be stressed that FBM stem cells retrieved at their optimal
      stage of hematopoiesis (16-20 weeks) may be the cells of choice for both
      therapeutic cellular reconstitution and gene targeting.

PMID- 14646411
TI  - In utero hematopoietic cell transplantation: what are the important questions?
AB  - The treatment of congenital hematologic disorders before birth by in utero
      hematopoietic stem cell transplantation remains a challenging goal. Although
      success has been achieved in X-linked severe combined immunodeficiency, the
      approach has failed in all other disorders attempted thus far. In this review, we
      examine relevant experimental data from the perspective of an analysis of why
      failure has occurred. We will also attempt to pose the important questions that
      will need to be answered prior to further clinical attempts to treat most target
      disorders by this approach.

PMID- 14646412
TI  - The intracoelomic route: a new approach for in utero human cord blood stem cell
      transplantation.
AB  - The intracoelomic route for in utero hematopoietic stem cell transplantation has
      been evaluated in pre-immune fetal sheep and the engraftment characteristics
      defined. Twelve ovine fetuses (gestational ages: 40-45 days) received
      intracoelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34
      selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment
      was evaluated from cell suspension of the liver, spleen, bone marrow and thymus
      by flow cytometry, cloning assays and polymerase chain reaction (PCR) analysis
      for human beta(2)-microglobulin gene. The engraftment of liver samples was also
      evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR),
      fluorescent in situ hybridization (FISH) and immunohistochemistry. Four fetuses
      (33%) aborted shortly after intracoelomic transplantation and were not evaluable
      for engraftment. Engraftment was detected in 4 fetuses obtained from cesarean
      delivery on day 70 after transplantation of CD3-depleted cord blood cells. The
      degree of engraftment in these 4 fetuses ranged from 6 to 22% in the different
      organs (as revealed by antigenic analysis of human CD45 with flow cytometry).
      Three fetuses obtained after cesarean section at 102 (No. 435184) and 105 (Nos
      915293, 037568) days and 1 fetus delivered at term, which received CD34-selected
      cord blood cells, had human engraftment with 10, 32, 20 and 10% CD45+ cells in
      bone marrow, respectively. A further check of human chimerism was done at 1 year
      after birth of the fetus delivered at term and 7.6% of bone marrow chimerism was
      detected. In 6 out of 8 fetuses evaluable for human engraftment, chimerism was
      confirmed by PCR analysis for human beta(2)-microglobulin which also identified
      human cells in brain, spinal cord, heart, lung and skeletal muscle. On liver
      samples, FISH and RT-PCR confirmed the xenograft of human cells and the
      immunohistochemical analysis detected human markers of hematopoietic and hepatic
      lineage of differentiation. This preliminary study indicates that intracoelomic
      transplantation of human hematopoietic stem cells in fetal lambs is feasible and
      effective in terms of hematopoietic engraftment.

PMID- 14646413
TI  - The sheep model of in utero gene therapy.
AB  - Once its full clinical potential has been realized, hematopoietic stem cell based
      gene therapy (GT) promises to cure a wide array of both inborn and acquired
      diseases. For many genetic disorders, early onset and irreparable tissue and
      organ damage necessitate innovative methods that allow therapeutic intervention
      early in development, if a full cure is to be realized. Performing GT in utero
      would allow early correction prior to disease onset and is thus one of the few
      therapeutic modalities that could promise the birth of a healthy infant. Several
      features of the developing fetus may circumvent obstacles that have thus far been
      observed in GT trials. For example, the immune naivete of the early gestational
      fetus may evade immune reactions to the vector and transgene product.
      Furthermore, fetal exposure to foreign antigens can result in sustained
      tolerance, suggesting that induction of tolerance to the vector/transgene product
      could allow postnatal treatment to be performed successfully. In addition to
      these immunologic advantages, the fetal hematopoietic system promises to be more
      amenable to retrovirus-mediated gene transfer than either the neonate or adult as
      a result of both proliferation and expansion of the stem/progenitor cell pool
      that take place during fetal development. To investigate whether these
      characteristics of the developing fetus could be used to advantage to efficiently
      transduce hematopoietic stem cells, we developed an approach to in utero GT, in
      which retroviral vectors were directly injected into the peritoneal cavity of
      preimmune fetal sheep. This approach resulted in the transfer and long-term (>5
      years) expression of exogenous genes within the hematopoietic system of primary
      and secondary recipients, albeit at relatively low levels that would not likely
      be therapeutic in most diseases. These studies also demonstrated that the direct
      injection of retroviral vectors into preimmune fetal sheep results not only in
      the successful transduction of long-term engrafting hematopoietic stem cells, but
      also in the widespread distribution of vector to all other tissues examined,
      including the reproductive organs. In an effort to increase the hematopoietic
      cell transduction to clinically relevant levels, we repeated our initial studies
      with 1,000-fold higher titer vectors. This led to only a modest (two- to
      fourfold) increase in the transduction levels, suggesting that factors other than
      absolute vector dosage were responsible for the low levels of gene transfer. For
      this reason, we have more recently begun evaluating the effect of recipient
      gestational age on the efficiency of gene transfer to both hematopoietic and
      nonhematopoietic tissues. Thus far, we have observed an inverse relation between
      the gestational age at the time of vector administration and the level of
      transduction and expression of the transgene within the hematopoietic system,
      such that fetuses injected earlier in gestation have higher levels of
      hematopoietic cell transduction. These elevated levels have persisted for at
      least 1 year after injection, suggesting that the enhancement is at the level of
      primitive stem/progenitor cells. When analyzing the liver sections from animals
      that had received the vector at different gestational ages, we also observed an
      inverse correlation between recipient age and efficiency of gene transfer to the
      hepatocytes, such that a high efficiency of gene transfer occurred at early ages,
      while very little occurred at later stages of gestation. In contrast to the
      findings in the hematopoietic system and in the liver, analysis of the lungs of
      these same animals revealed that the efficiency of transduction of
      nonhematopoietic lung tissue increased with increasing gestational age. These
      results demonstrate that both hematopoietic cells and nonhematopoietic cells
      within liver and lung are transduced following direct injection of murine
      retroviral vector supernatants into the peritoneal cavity of preimmune fetal
      sheep and suggest that the developmental stage of each organ at the time of
      injection may determine its etermine its susceptibility to in utero gene
      transfer.

PMID- 14646414
TI  - The fetal Doppler mechanical PR interval: a validation study.
AB  - OBJECTIVE: To evaluate the accuracy of pulsed Doppler-derived fetal PR interval
      measurements obtained by physicians participating in a multicenter prospective
      fetal echocardiographic study. METHODS: Echocardiograms on healthy fetuses were
      performed and evaluated by 15 pediatric cardiologists/perinatologists across the
      United States who are participating in a larger clinical trial involving fetuses
      at risk for autoantibody-associated congenital heart block. Prior to enrolling
      women in the main trial, each physician was provided with a teaching tape to
      demonstrate how the pulsed Doppler-derived PR interval is measured. The procedure
      involves placing a gated pulsed Doppler sample volume in the left ventricle at
      the junction of the anterior leaflet of the mitral valve and the left ventricular
      outflow tract in an apical 5-chamber view, and simultaneously obtaining left
      ventricular filling and emptying. Time intervals are measured from the onset of
      the mitral A wave (atrial systole) to the onset of the aortic pulsed Doppler
      tracing (ventricular systole). This represents the mechanical PR interval. Each
      physician measured the pulsed Doppler-derived fetal PR interval on 5 different
      subjects recruited from the physician's specific site. To validate each
      physician's technique, the tapes were sent to a central facility and the same
      intervals were remeasured by an experienced central reader (D.M.F.). A physician
      was determined to have adequate ability to measure the fetal PR interval if all 5
      measurements were within +/- 30 ms of the central reader's measurements, where 30
      ms corresponds to 25% of the mean observed in normative PR interval data. This
      difference was deemed to be the minimum clinically important difference in
      Doppler PR interval. RESULTS: Fourteen of the 15 physicians were considered to
      have adequate ability to measure the fetal PR interval according to our
      established criterion. The overall mean difference between the physicians and the
      central reader's measurements was -0.26 +/- 11.04 ms (p = 0.84). In addition, 95%
      of the observed differences were included in the interval (-22.23 to 21.81),
      which is well within our clinically acceptable range of +/- 30 ms. CONCLUSIONS:
      The pulsed Doppler assessment of the mechanical PR interval in the fetus can be
      accurately performed after minimal training. This technique may be a valuable
      tool for identification of early and potentially reversible conduction
      abnormalities in fetuses at risk for more advanced and permanent forms of heart
      block associated with maternal antibodies to SSA/Ro-SSB/La.

PMID- 14646415
TI  - Abnormal umbilical cord Doppler sonograms may predict impending demise in fetuses
      with sacrococcygeal teratoma. A report of two cases.
AB  - OBJECTIVE: To identify factors predictive of fetal demise in fetuses with
      sacrococcygeal teratoma (SCT). METHOD: The recent management of monochorionic
      twins discordant for a large SCT and a singleton with a large SCT was reviewed.
      RESULTS: Serial fetal echocardiography and ultrasonography with Doppler flow
      measurements documented rapid growth of the SCT in both cases with a relatively
      modest increase in combined cardiac output. No placentomegaly or hydrops was
      observed at any time. In both fetuses with SCT, evolution of abnormal umbilical
      artery waveforms was observed with the ultimate development of reversed end
      diastolic umbilical arterial flow that was followed by sudden fetal demise.
      CONCLUSION: Death in these 2 fetuses with large SCTs in the absence of
      placentomegaly/hydrops or hemodynamic changes suggestive of evolving high-output
      failure suggests a previously unrecognized mechanism of death in fetuses with
      large rapidly growing SCTs. In these cases, fetal demise may only be heralded by
      abnormal umbilical artery waveforms that progress to the premorbid observation of
      reversed diastolic umbilical artery blood flow. Umbilical artery waveform
      analysis should be closely monitored with other hemodynamic parameters in fetuses
      with large SCTs. In such fetuses, depending on the gestational age, abnormalities
      in umbilical artery waveform should be considered indications for early delivery
      or in utero intervention to prevent fetal demise.

PMID- 14646416
TI  - Fetal surgery for congenital diaphragmatic hernia and pulmonary sequestration
      complicated by postnatal diagnosis of transposition of the great arteries.
AB  - This report describes the case of a neonate who underwent fetal surgery for
      congenital diaphragmatic hernia (CDH) and pulmonary sequestration. His postnatal
      management was complicated by the additional diagnosis of transposition of the
      great arteries (TGA). TGA is particularly difficult to diagnose in the fetus.
      This triad has not previously been documented in the literature. Clinicians
      should have a high index of suspicion for associated anomalies, especially
      cardiac, when evaluating and counseling a pregnancy complicated by CDH.

PMID- 14646417
TI  - Association of undetectable unconjugated estriol on multiple marker screening
      with steroid sulfatase deficiency.
AB  - OBJECTIVE: To determine whether all patients with undetectable unconjugated
      estriol (uE3) on multiple marker screening (MMS) are carriers for steroid
      sulfatase (STS) deficiency. METHODS: This is a retrospective review of 65
      pregnancies with undetectable uE3 on MMS. RESULTS: Of the 65 pregnancies, there
      were 21 that continued, 40 spontaneous losses, 2 lost to follow-up and 2 elective
      terminations. Of the 21 continuing pregnancies, 15 were determined to be carriers
      of the STS deletion. Twenty-seven of the 40 pregnancy losses were associated with
      elevated alpha-fetoprotein (AFP); about half of the losses were shown to have
      occurred prior to sampling. CONCLUSION: Patients with undetectable uE3 are likely
      to be carriers of the STS deletion, except those with associated elevated AFP.
      Elevated AFP with undetectable uE3 on MMS is a marker of preexisting or impending
      fetal demise.

PMID- 14646418
TI  - Prenatal diagnosis of congenital diaphragmatic hernia in a McFadden Kalousek type
      2 triploid fetus.
AB  - Triploidy is characterized by an extra haploid set. We report a rare case of a
      prenatally diagnosed digynic type (McFadden/Kalousek type 2) triploid fetus with
      congenital diaphragmatic hernia (CDH). Prenatal ultrasonographic examination
      allows reliable detection of CDH and it is therefore of great importance for
      proper parental counselling, as well as performing fetal karyotype for associated
      chromosomal anomalies.

PMID- 14646419
TI  - Doppler measurements in fetoplacental vessels after maternal betamethasone
      administration.
AB  - OBJECTIVE: To observe the influence of maternal betamethasone administration for
      fetal lung maturation on the arterial, venous and intracardiac blood flow of the
      fetus and the uterine arteries. METHODS: Twenty-seven women with singleton
      pregnancies were examined before the first, and 30 min and 8, 24, 48 and 72 h
      after the second of two single doses of 8 mg of betamethasone. We recorded blood
      flow velocity waveforms of the umbilical artery (UA), the middle cerebral artery,
      the uterine arteries, the ductus venosus, the inferior vena cava and the right
      hepatic vein, the pulmonary trunk, the ductus arteriosus and the right and left
      intraventricular inflow of the heart. RESULTS: The resistance index of the UA
      showed a significant transient decrease 30 min (p = 0.024) after the second
      betamethasone dose. The peak systolic velocity of the ductus arteriosus increased
      significantly 30 min after the 2nd dose (p = 0.009) and then returned to non
      significant values. No significant change was observed in any of the other
      vessels. CONCLUSION: Betamethasone causes short-term changes in fetal blood flow.
      However, this effect seems to be mild and reversible and does not appear to
      contraindicate the use of corticosteroids to promote fetal lung maturation.

PMID- 14646420
TI  - Identification of Macrosomic, normal and intrauterine growth retarded neonates
      using the modified Neonatal Growth Assessment Score.
AB  - OBJECTIVE: Separation of Macrosomic, normal and intrauterine growth retarded
      (IUGR) neonates using the modified Neonatal Growth Assessment Score (NGAS).
      METHODS: A sample of 23 neonates with evidence of growth acceleration and 74
      neonates classified as normal or IUGR in a previous study was used in this
      investigation. The prenatal growth of all neonates had been studied
      longitudinally with ultrasound. From the data collected, Rossavik models
      describing the growth trajectories of head circumference (HC), abdominal
      circumference (AC), thigh circumference (ThC), femur diaphysis length, head cube
      (A) and abdominal cube (B) were specified. These models were used to predict
      birth weight (WT), crown-heel length (CHL), HC, AC and ThC at birth. Actual birth
      measurements of WT, CHL, HC, AC and ThC were evaluated using age-specific normal
      size curves and compared to predicted measurements by means of the growth
      potential realization index (GPRI). GPRI values were evaluated by comparison to
      previously established normal ranges and used to calculate Neonatal Growth
      Assessment Scores (NGAS(5)). NGAS(5) values, together with assessments of
      anatomical measurements and GPRI values, were used to establish macrosomic,
      normal and IUGR groups. Principal components analysis was applied to the sets of
      GPRI values available for each neonate to provide a principal component score for
      separating macrosomic and normal neonates (m(2)NGAS(51)) or one to separate
      macrosomic, normal and IUGR neonates (m(3)NGAS(51)) using linear discriminant
      analysis. The groups identified by these multivariate methods were compared to
      the original classification and their characteristics evaluated. RESULTS: The
      m(2)NGAS(51) and a boundary value of 207.5% separated macrosomic and normal
      neonates with an accuracy of 97.3%. The m(3)NGAS(51) and boundary values of 210.0
      and 182.5% separated macrosomic, normal and IUGR neonates with an accuracy of
      96.9%. No single GPRI value or anatomical measurement could achieve these levels
      of accuracy. All normal infants were AGA but only 45.5% of the IUGR group were
      SGA and only 60.9% of the macrosomic group were LGA. Thirteen different types of
      IUGR and eleven different types of macrosomia were identified based on GPRI
      values. CONCLUSION: The modified NGAS accurately separates macrosomic, normal and
      IUGR neonates although growth abnormalities are expressed in different ways in
      different individuals.

PMID- 14646421
TI  - Massive feto-maternal haemorrhage with good perinatal outcome following failed
      external cephalic version.
AB  - OBJECTIVE: To reinforce the risk of feto-maternal haemorrhage associated with
      external cephalic version for breech presentation. METHOD: A single case report
      with a literature review. RESULTS: Our case report was associated with the
      largest feto-maternal haemorrhage following external cephalic version reported so
      far. The perinatal outcome in this case was favourable despite a significant
      amount of fetal haemorrhage. The literature review did include cases with
      unfavourable outcomes. No reliable method of monitoring fetuses with feto
      maternal haemorrhage has been reported, although middle cerebral artery Doppler
      studies appear to show promise. CONCLUSION: External cephalic version is useful
      in the management of breech presentations at term, but it is not without risks
      and clinicians need to be aware of this.

PMID- 14646422
TI  - Significant fetal pulmonary regurgitation as a possible prenatal sign of aorto
      pulmonary window in the fetus with intrauterine growth retardation. A case
      report.
AB  - We report a fetal congenital heart defect - aorto-pulmonary window - found at
      autopsy, which coexisted with a significant holodiastolic pulmonary regurgitation
      seen during a routine echocardiography in a fetus with intrauterine growth
      retardation and multiple anomalies.

PMID- 14646423
TI  - Prenatal paternity testing using DNA extracted from coelomic cells.
AB  - OBJECTIVE: Prenatal paternity testing can be performed following invasive
      prenatal diagnosis with amniocentesis or CVS. Coelocentesis is a new technique
      that could be used as an alternative method early in the first trimester of
      pregnancy. The aim of this study is to investigate the potential use of the DNA
      extracted from coelomic cells in the prenatal paternity testing. METHODS:
      Coelocentesis was performed in 20 singleton pregnancies at 7-9 weeks of gestation
      immediately before surgical termination of pregnancy. Chorionic cells from the
      placenta and blood cells from the parents were processed by the standard salt
      extraction method. Two loci, TPO and Apo B, were used for paternity testing in
      the DNA of coelomic cells, chorionic cells and blood cells. RESULTS: There was
      concordance in the results obtained from the coelomic cells and chorionic villi.
      In two cases only the polymorphisms used were not conclusively informative for
      paternity exclusion. CONCLUSIONS: Coelomic cells are potentially useful for early
      paternity testing.

PMID- 14646424
TI  - Complete chorioamniotic membrane separation. Case report and review of the
      literature.
AB  - We present a patient who developed complete chorioamniotic membrane separation
      (CMS) in two consecutive pregnancies. The first pregnancy ended with an
      intrauterine fetal death at 25 weeks of gestation. The entire separated amniotic
      sac had twisted around the umbilical cord. In the subsequent pregnancy, a
      complete CMS was diagnosed at 34 weeks of gestation. In both pregnancies, the
      patient underwent an early 2nd-trimester genetic amniocentesis. A review of the
      literature shows that extensive CMS is associated with miscarriage, in utero
      fetal death, umbilical cord complications, and preterm delivery. Most reported
      cases occurred after invasive intrauterine procedures.

PMID- 14646425
TI  - Intrauterine myelomeningocele repair: effect on short-term complications of
      prematurity.
AB  - OBJECTIVE: To determine whether short-term complications of prematurity are
      affected by intrauterine myelomeningocele repair. METHODS: Medical records of the
      first 100 infants undergoing intrauterine myelomeningocele repair (IUMR) at the
      Vanderbilt University Medical Center were reviewed. Infants born at <34 weeks'
      gestation were identified. Two controls were identified for each IUMR infant.
      Controls were matched for gestational age, sex, birth weight, antenatal steroids,
      and mode and month of delivery. Development of respiratory distress syndrome,
      intraventricular hemorrhage, and chronic lung disease and days on ventilator and
      length of hospital stay were recorded. The results are expressed as mean values
      and ranges. Comparison of data between groups was performed using the Mann
      Whitney U test. Categorical data were compared using the chi-square test and
      Fisher's exact test. p </= 0.05 was considered statistically significant.
      RESULTS: One hundred infants underwent IUMR. Forty-four infants were born at <34
      weeks of gestation. Complete data were available on 37 infants. Seventy-four
      matched controls were studied. Eleven infants from the IUMR group and 23 infants
      from the control group developed respiratory distress syndrome (29.7 vs. 31.1%; p
      = 0.8). Six infants from the IUMR group and 13 infants from the control group
      developed chronic lung disease (16.2 vs. 17.5%; p = 0.9). The length of stay was
      28 (range 2-82) days for the IUMR group and 24 (range 1-99) days (p = 0.09) for
      the control group. There was also no significant difference between groups with
      regard to intraventricular hemorrhage and days on ventilators. CONCLUSION: There
      is no difference between short-term complications of prematurity following IUMR
      and those associated with prematurity resulting from other causes.

PMID- 14646426
TI  - Can three-dimensional ultrasound be used for the assessment of the fetal lung
      volume in cases of congenital diaphragmatic hernia?
AB  - We report on 2 fetuses with congenital diaphragmatic hernia (CDH) in whom the
      fetal lung volumes were estimated by three-dimensional ultrasound and the results
      compared with the postmortem lung volume measurements. Both examiners
      (sonographer and pathologist) were blinded to each other's results. The 1st case
      was a right CDH diagnosed at 20 weeks of gestation. The 2nd case was a left CDH
      diagnosed at 22 weeks of gestation. Both pregnancies were terminated upon request
      of the parents. Three-dimensional ultrasound estimation of the fetal lung volume
      was performed 1 day before termination of pregnancy using the technique of
      rotation of the three perpendicular planes. The left and right lung volumes
      estimated by three-dimensional ultrasound were 3.88 and 1.87 cm(3), respectively,
      in the 1st case and 0 and 5.52 cm(3), respectively, in the 2nd case. On
      postmortem examination, the left and right lung volumes were 3.0 and 2.2 cm(3),
      respectively, in case 1 and 1.1 and 5.6 cm(3), respectively, in case 2. This
      suggests that a three-dimensional estimation of pulmonary volumes may be
      correlated with postmortem findings in cases with CDH.

PMID- 14646427
TI  - In utero allotransplantation of fetal hepatocytes in primates.
AB  - OBJECTIVE: Because intrauterine transplantation of fetal hepatocytes could become
      an effective approach for treating severe genetic disorders of the liver, the
      objective of this study was to demonstrate the feasibility of in utero
      allotransplantation of fetal hepatocytes in a nonhuman primate model using direct
      intraparenchymal administration of donor cells. METHODS: Fetal primary
      hepatocytes were isolated from 3 fetal primates (MACACA MULATTA) at 89-120 days
      of gestation, and cryopreserved. When a recipient was available, the cells were
      thawed and transduced by a beta-galactosidase-expressing retrovirus (3 cases) or
      labelled with a fluorescent dye (4 cases). Hepatocytes were infused directly into
      the fetal liver under surgical visual control. Engraftment was assessed by
      surgical liver biopsies taken 8-60 days following transplantation. RESULTS: Six
      recipients survived until liver biopsy, and 1 died during the surgical procedure.
      There was no evidence of engraftment in the 3 fetuses that received genetically
      marked hepatocytes. All 3 monkeys who received 20-25 x 10(6) hepatocytes from an
      89-day-old donor labelled with fluorescent dye had positive liver biopsies 8-11
      days following intrauterine transplantation. CONCLUSIONS: In utero
      allotransplantation of fetal hepatocytes is feasible in the nonhuman primate, and
      direct intraparenchymal administration enables short-term detection of persisting
      donor hepatocytes.

PMID- 14646428
TI  - Prenatal demonstration of major aortopulmonary collateral arteries with tetralogy
      of Fallot and pulmonary atresia.
AB  - Major aortopulmonary collateral arteries were prenatally demonstrated in a case
      of tetralogy of Fallot and pulmonary atresia (TOF-PA). Color Doppler and pulsed
      Doppler ultrasonography revealed abnormal arteries arising directly from the
      descending aorta. An aortogram after birth confirmed two collateral arteries
      arising from the descending aorta and one from the left subclavian artery. Fetal
      echocardiography was essential for the diagnosis of TOF-PA, but further
      examination was needed to find collateral arteries, which provided useful
      information for management after birth.

PMID- 14646429
TI  - Functional aortic stenosis diagnosed in fetal period.
AB  - We report a case of fetal congenital heart disease prenatally diagnosed as
      critical aortic valve stenosis at 25 weeks of gestation. Fetal echocardiography
      demonstrated severe mitral regurgitation, aortic valve stenosis,
      hypocontractility of the left ventricle, and showed retrograde flow in the aortic
      arch like HLHS (hypoplastic left heart syndrome). However, soon after delivery,
      improvement in the baby's hemodynamics and myocardial contractility were
      recognized without any treatment.

PMID- 14646430
TI  - Imaging studies in the diagnosis of urogenital trauma.
AB  - Polytraumatized patients often present with urological injuries. After
      hemodynamic stability is maintained urologists are consulted to evaluate
      diagnostic and therapeutic interventions. The following article describes how to
      handle the work-up of patients with injuries to specific urogenital organs: the
      importance of clinical examination, ultrasonography, computed tomography (CT),
      magnetic resonance imaging (MRI), angiography as well as organ-specific
      radiologic studies such as intravenous pyelography or cystography are discussed.
      CONCLUSION: Even though injuries to the urogenital tract are rarely initially
      life--threatening, a fast, reliable and adequate diagnostic algorithm has to be
      established to avoid any delay of specific treatment. Urologists should be
      familiar with the indications, range and accuracy of these procedures in the
      diagnosis of urogenital trauma.

PMID- 14646431
TI  - Outcome and safety of extracorporeal shock wave lithotripsy as first-line therapy
      of lower pole nephrolithiasis.
AB  - INTRODUCTION: The aim of this study is to assess the efficiency of extracorporeal
      shock wave lithotripsy (ESWL) as initial therapy for isolated lower pole kidney
      stones smaller than 20 mm. PATIENTS AND METHODS: During a 24-month period 116
      patients with previously untreated single stones under 20 mm in diameter were
      treated with a Dornier lithotripter S. They were analyzed with regard to stone
      site and size, number of ESWL sessions, auxiliary measures, retreatment rates,
      complications and the time taken for stone clearance. RESULTS: 76 patients
      (65.5%) became stone free, 50 of them (43.1%) within 3 months after ESWL.
      Depending on stone size the stone-free rates were 67.1% for patients with a stone
      diameter of <10 mm (59 of 88 patients), and 60.7% for stone diameters between 10
      and 20 mm (17 of 28 patients). Complications during and after treatment were
      rare, i.e. the necessity of ureteral stent insertion due to colic (n = 10),
      endoscopic stone removal (n = 2), acute pyelonephritis (n = 1), stonestreet (n =
      1) and 1 case of hematoma not requiring intervention. The recurrence rate during
      follow-up (13.2-36.9, mean 25.0 months) was low: 16 patients (13.8%) had
      recurrent or persistent stones, and 74 patients (63.8%) had no evidence of
      urolithiasis. CONCLUSIONS: ESWL is a safe and efficient first-line therapy for
      treatment of isolated small lower pole kidney stones with acceptable stone-free
      rates, low morbidity, few complications and a low stone recurrence rate.

PMID- 14646432
TI  - Results of extracorporeal shock wave lithotripsy with a new electrohydraulic
      shock wave generator.
AB  - OBJECTIVE: Since 1999, the lithotriptor LDM (Philips, Germany) is used routinely
      for treatment of urinary stones in our department. We evaluated the complication
      rate and treatment success of extracorporeal stone treatment with the new
      lithotriptor. MATERIAL AND METHODS: We performed a prospective, two-step clinical
      study: (1) Complication rate: From January to May 1999, 312 consecutive
      treatments in 225 patients (136 male, 89 female) were evaluated. (2) Success
      rate: From February to April 2000, 88 consecutive patients (61 male, 27 female)
      with 113 concrements were evaluated. RESULTS: (1) Complication rate: Overall
      complication rate was 10%. Most of them were minor complications. Most
      significant complications were subcapsular renal hematomas, which were detected
      by routinely performed renal ultrasound in 1%. (2) Success rate: After single
      treatment, overall success rate was 87%. 15 of 16 in situ treated ureteral stones
      (94%) were sufficiently disintegrated by a single treatment. Disintegration rates
      after single treatment were 93.6% for renal stones smaller than 1 cm and 86% for
      renal stones 1-2 cm, respectively. CONCLUSIONS: Stone therapy by SWL with the new
      lithotriptor LDM is a highly effective therapy of renal and ureteral stones and
      has a low complication rate.

PMID- 14646433
TI  - Adrenalectomy: defining its role in the surgical treatment of renal cell
      carcinoma.
AB  - OBJECTIVES: With the recent widespread use of modern imaging techniques, the
      frequency of small low-stage renal cell carcinomas (RCC) has grown considerably,
      giving rise to more conservative surgical approaches. We evaluated the
      characteristics of adrenal involvement and the accuracy of computerized
      tomography (CT) in the diagnosis of RCC, defining the real need for adrenalectomy
      during surgical treatment. METHODS: The medical records of 201 patients
      undergoing radical nephrectomy and ipsilateral adrenalectomy for localized or
      advanced RCC, from 1996 to 2002, were analyzed, retrospectively. We considered 76
      with stage T1-2 disease and 125 with T3-4N0-1M0-1 disease. In all cases a blinded
      review of the preoperative abdominal CT was performed. Histopathology records of
      the surgical specimens were examined to determine the accuracy of the CT in
      identifying adrenal involvement by RCC. RESULTS: The overall incidence of adrenal
      metastasis was 4.4%. The mean renal tumor size in patients with adrenal
      involvement was 7.8 cm. The tumor stage correlated with a probability of adrenal
      spread (p < 0.05), with T1-2 tumors accounting for 1.3% of cases only. The
      adrenal gland was diagnosed as abnormal on preoperative CT in 21 patients
      (10.4%). CT scan demonstrated 88.8% sensitivity, 92.1% specificity, 99.4%
      negative predictive value and 34.7% positive predictive value for adrenal
      involvement by RCC. CONCLUSIONS: Adrenal involvement is not likely in patients
      with localized early stage RCC and adrenalectomy can be omitted in such cases,
      particularly when CT is negative. However, in selected patients with large high
      risk tumors, radical nephrectomy, including removal of the ipsilateral adrenal
      gland, should be performed.

PMID- 14646434
TI  - Subinguinal microsurgical varicocelectomy: evaluation of the results.
AB  - INTRODUCTION: Varicoceles have been established to be the commonest correctable
      cause of male infertility. Among the various methods available, microsurgical
      varicocelectomy has one of the lowest complication rates with low failure.
      PATIENTS AND METHODS: Over a 4-year period, 100 patients underwent microsurgical
      varicocelectomy at our center. One hundred and forty-four surgeries were
      performed on 90 of these patients through a subinguinal approach and these form
      the study group. Only clinically diagnosed varicoceles were operated. Pre
      operative semen values were compared with the post-operative values and
      statistical analysis performed using a non-parametric test. All 90 patients
      provided at least 1 post-operative semen report 3 months after surgery while 50
      are on complete follow-up. RESULTS: Sperm count improved in 71% patients, normal
      motility in 60% and normal morphology in 49%. Seventeen of the 50 patients on
      full follow-up (34%) achieved pregnancy, with 16 of these being spontaneous. All
      patients achieving pregnancy showed improvement in sperm count, 13 improved in
      motility and 12 in morphology. All improvements were statistically significant.
      There were 21 (14.6%) minor complications with no testicular atrophy and 1
      recurrence. CONCLUSION: Microsurgical varicocelectomy is a safe and effective
      option for the management of varicocele-induced male infertility. It leads to
      improvement in all semen parameters and increases the possibility of spontaneous
      pregnancies.

PMID- 14646435
TI  - Varicoceles in adolescents and young adults after surgery for hepatosplenic
      schistosomiasis.
AB  - INTRODUCTION: This case-control study aimed at evaluating testicular volume,
      pubertal and genital development, and incidence of varicoceles in adolescents and
      young adults after surgery for hepatosplenic schistosomiasis associated with
      bleeding oesophageal varices. PATIENTS AND METHODS: The study involved 26 young
      males with schistosomiasis who were submitted to splenectomy, left gastric vein
      ligature, and auto-implantation of splenic tissue in the major omentum during
      childhood. The mean follow-up period was 4 years after surgery. The control group
      included 15 healthy volunteers from a school in the same region where the cases
      lived. They were randomly selected, matched by age and epidemiological
      characteristics, and had schistosomiasis ruled out. All participants underwent
      thorough clinical and ultrasound examinations. Special attention was paid to
      sexual characteristics, testicular ultrasonography, and Doppler flowmetry of
      spermatic veins. RESULTS AND CONCLUSIONS: The patients with schistosomiasis had
      significant deficits in pubertal and genital development and in testicular
      volume, especially the left one, and a high incidence of varicoceles (61.5%)
      without a straight association with testicular atrophy.

PMID- 14646436
TI  - Ureaplasma urealyticum and Mycoplasma hominis in men attending for routine semen
      analysis. Prevalence, incidence by age and clinical settings, influence on sperm
      characteristics, relationship with the leukocyte count and clinical value.
AB  - AIM: To investigate the clinical value of the screening of Ureaplasma urealyticum
      and Mycoplasma hominis in routine semen analysis. MATERIAL AND METHODS: Semen
      samples of 234 patients with several clinical settings (infertility, varicocele,
      spontaneous abortion, genital infections, undescended testicles, hemospermia,
      etc.) were distributed in three study groups: group 1--negative cultures; group 2
      -normal colonization (< or =10(3) colony-forming units (cfu)/ml), and group -
      pathogenic colonization (>10(3) cfu/ml). Frequency rates, incidence by age and
      clinical settings, association with abnormal sperm characteristics (density,
      vitality, motility and morphology) and with the leukocyte count were
      investigated. RESULTS: Prevalence of U. urealyticum was higher than M. hominis (<
      or = 10(3) cfu/ml: 28.2 vs. 24.8%; >10(3) cfu/ml: 20.5 vs. 13.3%). No difference
      was detected on the incidence of mycoplasmas by age and clinical settings, as
      well as in regard to the mean values of sperm density, vitality, motility, oval
      headed sperm and leukocyte count (p > 0.05). CONCLUSION: In spite of the high
      incidence of mycoplasmas, not enough information was available regarding the
      influence of these microorganisms on the sperm quality and their relationship
      with the leukocyte count. Therefore, screening of U. urealyticum and M. hominis
      for routine semen analysis is not clinically relevant.

PMID- 14646437
TI  - Nephrostomy tract dilation using a balloon dilator in percutaneous renal surgery:
      experience with 95 cases and comparison with the fascial dilator system.
AB  - INTRODUCTION: Nephrostomy tract dilation is one of the important steps of
      percutaneous renal surgery. In this study, we present our initial experience with
      the balloon dilator in 95 patients and compare our results retrospectively with a
      group of 30 patients in whom Amplatz dilators were used. PATIENTS AND METHODS:
      The medical records of 95 patients who underwent percutaneous renal operations,
      including percutaneous nephrolithotomy and antegrade endopyelotomy, between
      September 1999 and September 2002 were reviewed. All procedures were performed
      using balloon dilators. The operative technique is the same as the other dilation
      procedures. Thirty consecutive patients who had previously undergone percutaneous
      renal surgery using the Amplatz dilators were taken as the control group and
      their charts were reviewed retrospectively, and the results compared with the
      results of patients in whom balloon dilation was used. RESULTS: There were no
      major perioperative complications or deaths in both groups. The mean operative
      time and tract formation times for the balloon dilation group and the Amplatz
      dilation group were 106.8 +/- 41.4 and 11.2 +/- 3.0, and 116.4 +/- 23.7 and 16.3
      +/- 2.4 min, respectively. Thirteen (13.7%) patients had significant bleeding and
      required blood transfusion in the balloon dilation group, whereas 5 (16.6%)
      patients had significant bleeding in the Amplatz dilation group. Collecting
      system perforation due to too far advancement of the dilator occurred in 11
      (11.6%) patients but there was no major parenchymal or vascular injury medially
      in the balloon dilation group. On the other hand, collecting system perforation
      occurred during sequential Amplatz dilation in 5 (16.6%) patients. CONCLUSION: We
      believe that the balloon system allows one-step dilation and shortens the
      dilation procedure. It may minimize bleeding which can occur during the stepwise
      fascial dilation. When using fascial dilators it is sometimes possible to go out
      of the collecting system by changing the size of the dilators. We think that
      balloon dilation may prevent these intraoperative and time-consuming situations.

PMID- 14646438
TI  - Stage I testicular seminoma: para-aortic and iliac irradiation with reduced dose
      after orchiectomy.
AB  - BACKGROUND AND PURPOSE: Radiotherapy remains the treatment of choice for patients
      with stage I seminoma. The aim of this study is to report preliminary results of
      reduced dose radiotherapy to ipsilateral pelvic and para-aortic lymph nodes.
      MATERIALS AND METHODS: Between February 1996 and December 2001, 53 patients with
      stage I testicular seminoma were treated with adjuvant radiotherapy after
      orchiectomy. The median age was 34 years (19-59 years). Four (7.5%) patients had
      a history of cryptorchidism. Eleven (20.8%) patients showed elevated beta-human
      chorionic gonadotropin. All patients had a radical inguinal orchiectomy and
      histopathological analysis yielded classic seminoma in 47 (88.7%), spermatocytic
      in 5 (9.4%) and anaplastic in 1 (1.9%) patients. A total of 19.6-20 Gy in 1.8- to
      2-Gy daily fractions was administered to the para-aortic and ipsilateral iliac
      lymphatics. RESULTS: Median follow-up time was 42 months (12-77 months). One
      patient developed para-aortic lymph node recurrence at month 28 of the follow-up.
      Five-year overall and disease-free survivals were 100 and 98%, respectively. Only
      grade I-II of the Radiation Therapy Oncology Group acute gastrointestinal
      complications without any severe late toxicity was detected. CONCLUSION: Reduced
      dose radiotherapy seems to be as effective as higher doses in the management of
      stage I seminoma with an acceptable toxicity.

PMID- 14646439
TI  - Is using lignocaine gel prior to flexible cystoscopy justified? A randomized
      prospective study.
AB  - OBJECTIVE: We evaluate the discomfort and efficacy of instilling 2% lignocaine
      gel (Instillagel) versus smearing water-soluble gel (Aquagel) around the flexible
      cystoscope and external urethral meatus in men undergoing flexible cystoscopy for
      the first time and the overall efficacy of lignocaine gel in completion of the
      procedure. MATERIALS AND METHODS: A total of 140 patients divided into two
      groups, were randomized for this study: group A (n = 70) received approximately
      11 ml of 2% lignocaine gel (Instillagel) intraurethrally for approximately 15
      min, while in group B (n = 70) approximately 10-15 ml of water-soluble gel
      (Aquagel) was smeared around the scope and external urethral meatus. Total
      completion time for each procedure was recorded. Primary outcomes were pain
      during instillation of lignocaine, during insertion of scope and cystoscopy. Pain
      was recorded by the patient using a 100-mm nongraphic rating visual analogue
      scale. Secondary outcome included procedure time and cost analysis. RESULTS: The
      majority of patients in both groups reported mild pain with VAS 3 or less
      throughout the whole procedure. No significant difference was noted in the two
      groups at any stage of the procedure. Use of lignocaine gel added approximately
      10 min to the procedure time. CONCLUSIONS: In our study there was no significant
      difference in patient discomfort between instilling lignocaine gel and smearing
      of Aquagel in completion of flexible cystoscopy. However, application of
      lignocaine gel added extra time, effort and cost to the procedure.

PMID- 14646440
TI  - Volume of nerve fibers in the stress-induced bladder of adult rats following
      capsaicin treatment.
AB  - INTRODUCTION: We have investigated the volume of nerve fibers in the rat urinary
      bladder following systematic exposure to cold-restraint stress and capsaicin
      treatment. MATERIALS AND METHODS: Adult Wistar albino rats were either exposed to
      cold-restraint stress (vehicle group) or treated with capsaicin before exposure
      to cold-restraint stress (capsaicin group). In the control group, animals were
      neither exposed to cold-restraint stress nor given capsaicin. From each group,
      samples of bladder were prepared for morphological investigation and
      stereological evaluation of the volume of nerve fibers. RESULTS: Stress exposure
      was associated with urothelial degeneration, a higher incidence and degranulation
      of mast cell profiles in the mucosa, and an increased volume of nerve fibers in
      the muscular layer of the bladder wall. Capsaicin treatment prevented the stress
      induced degenerative changes. In the capsaicin group, the volume of nerve fibers
      in the muscular layer was also significantly smaller than that in the stress
      group. CONCLUSIONS: Exposure of adult rats to capsaicin prevented the stress
      induced degeneration of the bladder and changed the volume of capsaicin-sensitive
      fibers in muscular layer. We conclude that capsaicin and related compounds may be
      useful in treating stress-induced bladder problems.

PMID- 14646441
TI  - Effects of diabetes on nitric oxide-mediated relaxations in male rat corpus
      cavernosum smooth muscle.
AB  - INTRODUCTION: We evaluated the effects of diabetes on nitric oxide-mediated
      relaxations and nitric oxide synthase activity in male rat corpus cavernosum
      smooth muscles. METHODS: Eight-week-old male rats were assigned to three groups:
      control (injected with the vehicle), DM (diabetes mellitus, induced by injection
      with 65 mg/kg streptozotocin), and TES (testosterone, testosterone supplemented
      after induction of diabetes). After 8 weeks, corpus cavernosum smooth muscle
      strips were mounted in an organ bath for isometric tension recordings. Electrical
      field stimulation (EFS, 2-ms pulse duration, 0.3-20 Hz and 3 s train) was applied
      to the strips precontracted with 30 microM phenylephrine. The microdialysis probe
      was inserted into the strip, and Krebs-Henseleit solution was perfused into the
      probe. The dialysate during EFS was collected, and the amount of NO(-)(2)/NO(
      )(3) (NOx) released in the dialysate was measured by the Greiss method. Sodium
      nitroprusside (0.1 nM to 10 mM) and carbachol (1 nM to 10 mM) were cumulatively
      added to the strips precontracted with 30 microM phenylephrine. RESULTS: EFS
      caused frequency-dependent relaxations and NOx releases of the strips.
      Pretreatment with N(omega)-nitro-L-arginine (100 microM) and tetrodotoxin (1
      microM) completely inhibited the relaxations and NOx releases. The maximum
      relaxation was significantly greater in the DM group than in the control or TES
      group. The release of NOx was significantly greater in the DM group than in the
      control or TES group. Sodium nitroprusside, the endothelium-independent
      vasodilator, relaxed the tissues in all three groups. There were no significant
      differences among control, DM and TES groups in the maximum relaxation to sodium
      nitroprusside. CONCLUSION: The present data suggest that diabetes enhances nitric
      oxide synthase activity and nitric oxide-mediated relaxations in the male rat
      corpus cavernosum by the reduced testosterone level in the diabetic animals.

PMID- 14646442
TI  - High-throughput tissue microarray analysis of erbB-2 gene amplification in
      urinary bladder cancer. A study of Bulgarian patients.
AB  - INTRODUCTION: Overexpression of the receptor Her-2 leads to increased
      proliferative response to epidermal growth factors which plays a key role in
      tumor development and growth. Increased oncoprotein level, in the majority of
      cases, is caused by erbB-2 gene amplification. To define the frequency of
      amplifications of erbB-2 in bladder cancer, and to determine their association
      with the tumor phenotype we utilized tissue microarray (TMA) approach. MATERIALS
      AND METHODS: We analyzed a TMA consisting of 159 transitional cell bladder
      carcinomas for erbB-2 gene amplification by dual-color FISH. RESULTS: The
      frequency of erbB-2 amplification was 5.3% of all successfully analyzed samples
      (4 of 75). It increased from minimally invasive (pT1) to muscle-invasive (pT2-4)
      tumors, as well as with advanced tumor grade (G1 to G2 to G3). All amplifications
      were cluster amplifications confirming the fact that erbB-2 amplification occurs
      intrachromosomally in bladder cancer. CONCLUSIONS: We concluded that despite its
      low incidence, erbB-2 amplification is of importance for the bladder tumor
      invasion and progression.

PMID- 14646443
TI  - Synchronous bilateral testicular germ cell tumor with different histology. Case
      report and review of the literature.
AB  - A rare case of synchronous bilateral testicular germ cell tumor of different
      histological type is described. We report the case of a 39-year-old man with this
      unusual condition and discuss the value of the histopathological diagnosis in
      therapy and prognosis. A thorough review of the literature is also presented, and
      for the first time the precise histological subtype of each reported tumor, as
      diagnosed by the authors of the original paper, is illustrated.

PMID- 14646444
TI  - Lingual metastasis from renal cell carcinoma management and review of the
      literature.
AB  - A case of anterior lingual swelling, which on excision biopsy was diagnosed as a
      secondary from renal cell carcinoma, is presented. We reviewed the indexed
      literature and present a review of the literature and current management of this
      uncommon problem.

PMID- 14646445
TI  - Renal smooth muscle tumor with features of lymphangioleiomyomatosis. Problems in
      histological diagnosis.
AB  - A 44-year-old woman with left kidney tumor involving the perirenal and
      retroperitoneal lymph nodes is presented. Imaging findings including
      ultrasonography and computerized tomography showed renal and para-aortic masses
      and no features of lymphangioleiomyomatosis or angiomyolipoma were seen. The
      histopathological examination was considered as a renal smooth muscle tumor with
      features of lymphangioleiomyomatosis. Diagnosis considerations, particularly
      histopathological, immunohistochemical and hormonal studies are discussed and we
      comment the distinction of this case from the benign mesenchymal tumors.

PMID- 14646446
TI  - Remission of idiopathic retroperitoneal fibrosis after sequential therapy with
      corticosteroids and tamoxifen.
AB  - The most favored therapy for idiopathic retroperitoneal fibrosis is the surgical
      relief of ureteral obstruction and use of corticosteroids to prevent recurrence.
      Although effective, long-term corticosteroid treatment could be associated with
      serious side effects. We would like to present a case of idiopathic
      retroperitoneal fibrosis treated successfully with intraperitonealization of the
      ureters and sequential therapy with steroids and tamoxifen to minimize the side
      effects.

PMID- 14646447
TI  - Mycotic aneurysm of the popliteal artery as a complication of intravesical BCG
      therapy for superficial bladder cancer. Case report and literature review.
AB  - A 67-year-old man was treated with maintenance intravesical BCG for superficial
      bladder cancer. As a culture-proven complication of this therapy, he developed
      general malaise, high fever, granulomatous hepatitis and a mycotic aneurysm in
      his left knee. All complications were treated successfully with antituberculous
      therapy. No vascular surgery was necessary. This case report again stresses the
      necessity to recognise complications of BCG treatment and to start adequate
      therapy as soon as possible.

PMID- 14646448
TI  - Severe neurotoxicity in tacrolimus-treated living kidney transplantation in two
      cases.
AB  - Two living kidney-transplant recipients under tacrolimus-based immunosuppressive
      therapy experienced severe neurotoxicity, with tonic-clonic seizures. In both
      cases the dosage reduction did not result in improvement of symptoms, which
      completely disappeared after modification of the immunosuppressive regimen from
      tacrolimus to cyclosporine. Severe neurotoxicity, with seizures or uncommon
      clinical features, such as serious myalgias, is not foreseeable. We recommend the
      conversion to cyclosporine-based immunosuppression in such cases.

PMID- 14646449
TI  - Inguinal fibrolipoma of the spermatic cord: discrepancies between clinical and
      histopathological findings.
AB  - Tumors of the spermatic cord are rare. Up to 20% are malignant and usually
      located in the paratesticular region. We report the rare case of an inguinal
      fibrolipoma of the spermatic cord with discrepancies between clinical and
      histopathological findings.

PMID- 14646450
TI  - Defense styles, impulsivity and suicide attempts in major depression.
AB  - BACKGROUND: The aim of our study was to identify if defense mechanisms are
      associated with impulsivity and lifetime suicide attempts in depressed patients.
      SAMPLING AND METHODS: The Defense Style Questionnaire, the Impulsivity Rating
      Scale and the Impulse Control Scale were used in 77 depressed inpatients.
      RESULTS: Impulsivity was correlated positively with immature and neurotic styles
      and negatively with mature style. Some but not all defense mechanisms were
      relevant in this respect. The number of lifetime suicide attempts was positively
      correlated not only with impulsivity, but also with immature style and to a
      lesser extent with neurotic style. Several defense mechanisms were involved in
      these correlations: undoing, projection, passive aggression, acting out,
      splitting and somatization. CONCLUSIONS: Like impulsivity, defense styles may be
      relevant to discriminate recurrent suicide attempters in depression. Prospective
      assessment of defense styles and suicide attempts in depression is needed.

PMID- 14646451
TI  - Subtypes of depressive episodes according to ICD-10: prediction of risk of
      relapse and suicide.
AB  - BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of depression
      with melancholic syndrome and depression with psychosis has not been
      investigated. SAMPLING AND METHODS: All patients in Denmark who had a diagnosis
      of a single depressive episode at their first ever discharge during a period from
      1994 to 1999 were identified. The risk of relapse leading to readmission and the
      risk of committing suicide were compared for patients discharged with an ICD-10
      diagnosis of a single depressive episode with and without melancholic syndrome
      and for patients with and without psychotic symptoms, respectively. RESULTS: In
      all, 1,639 patients had a diagnosis of depressive episode without psychotic
      symptoms, 1,275 patients a diagnosis with psychotic symptoms, 293 a diagnosis
      without melancholic syndrome, and 248 a diagnosis with melancholic symptoms at
      first discharge. The risk of relapse leading to readmission was greater for
      patients with psychotic symptoms than for patients without, but no difference was
      found between the two groups in the risk of committing suicide during follow-up.
      No differences were found in the risk of relapse leading to readmission or
      suicide between patients with and without melancholic syndrome. CONCLUSIONS: The
      ICD-10 categorization into depression with and without psychotic symptoms seems
      to be clinically and prognostically useful, whereas the ICD-10 subtyping into
      melancholic and non-melancholic syndrome does not seem to have any long-term
      predictive value.

PMID- 14646452
TI  - A retrospective comparison of inpatients with mixed and pure depression.
AB  - Some authors advocate a broadening of the narrow concept of mixed episodes in the
      direction of mania leading to the concept of mixed mania, and in the direction of
      depression leading to the concept of mixed depression. The latter has been little
      investigated so far. In the present article, we retrospectively compare 49
      patients with pure depression with 51 patients with mixed depression in terms of
      socio-demographic and clinical variables in order to contribute to the validation
      of the distinction between mixed and pure depression. Supporting this
      distinction, we observed that mixed depressive patients more frequently had past
      histories of bipolar disorder and alcohol abuse and had longer durations of
      hospital stay. These last two points remain significant even when we control for
      the effect of the association with bipolarity.

PMID- 14646453
TI  - Establishing the reliability of a verbal self-monitoring paradigm.
AB  - BACKGROUND: Auditory hallucinations in schizophrenia are associated with
      defective monitoring of inner speech. This process can be examined using a
      computerised task of verbal self-monitoring. Cognitive therapy for voices aims to
      improve the patients' self-monitoring ability, and changes in self-monitoring
      could be assessed using this task. Before using the paradigm in this way, we
      sought to determine its test re-test reliability. SAMPLING AND METHODS: 20 normal
      volunteers were tested on the paradigm on two occasions, 3 months apart. The task
      involved reading single adjectives under the following randomized conditions:
      reading aloud; reading aloud with acoustic distortion of their own voice; reading
      aloud with alien feedback (someone else's voice), and reading aloud with
      distorted alien feedback. Immediately after articulating each word, the
      participants were required to identify the source of the speech they heard
      ('self'/'other'/'unsure') via a button press. Response choice and reaction time
      were recorded. RESULTS: There was no change in error rate over the two testing
      occasions; however, participants had faster reaction times when tested for the
      second time. This reduction in reaction time was not specific to type of response
      (correct, error, unsure). CONCLUSIONS: Participants showed no evidence of
      practice on the paradigm in terms of making fewer errors or responding faster for
      correct responses. The overall reduction in reaction times on the second occasion
      may reflect increased familiarity with the task. The verbal self-monitoring
      paradigm appears to be a reliable measure, which could be used to evaluate
      changes in self-monitoring ability in hallucinators following psychological
      therapy.

PMID- 14646455
TI  - [Anesthesia and obstructive pulmonary disease].
AB  - The article deals with the problems of perioperative management of patient with
      respiratory disease. The impact of general and regional anesthesia on respiratory
      system is discussed. Risk factors of perioperative respiratory complications are
      reviewed as well as general means for reducing them. Issues of anesthetic
      management of patients with bronchial asthma and chronic respiratory disease are
      discussed, putting stress on preoperative optimization of respiratory function,
      choice of anesthetic technique and postoperative pulmonary rehabilitation.

PMID- 14646454
TI  - Antenatal depression and maternal-fetal attachment.
AB  - BACKGROUND: In recent years, attention has been turned to maternal mental health
      in relation to the mother-child relationship accompanying a widening in focus,
      i.e. taking into account not only the puerperium, but also the stage of
      pregnancy. This applies to studies that have revealed a connection between
      depression and maternal attachment in the postpartum period and late pregnancy.
      This study, however, was designed to evaluate the maternal-fetal relationship in
      the first and second trimesters, being the first one to address this issue in
      these early stages. SAMPLING AND METHODS: Zung's Self-Rating Depression Scale
      (ZSDS), the original Antenatal Maternal Attachment Scale (AMAS), and a
      questionnaire addressing peripheral factors were given to 216 pregnant women (3-6
      months of gestation) who visited the Nagoya University Hospital between September
      1998 and June 2001. RESULTS: Contrary to reports on the latter stages of
      pregnancy, no direct association was observed between depression in mothers and
      maternal-fetal attachment before fetal movement was perceived. CONCLUSION:
      However, education, form of employment, planning of pregnancy, and premenstrual
      mood changes were found to be associated with the ZSDS score (mean: 41.9), while
      form of employment, feelings regarding pregnancy, and sources of support were
      extracted as factors associated with the AMAS, which are of interest in terms of
      the subsequent association between depression and maternal-fetal attachment in
      the peri- and postnatal periods.

PMID- 14646456
TI  - [Principles of anesthesia for pulmonary surgery].
AB  - The aim of the article is to review principles of thoracic anesthesia for
      pulmonary surgery. This article is divided into three sections. Preoperative
      considerations include pulmonary evaluation and optimal pulmonary preparation.
      Intraoperative period considerations are monitoring requirements, choice of
      anaesthesia and the indications for providing one-lung ventilation. Postoperative
      problems of immediate life-threatening complications, management of mechanical
      ventilation and control of pain are discussed in the third part.

PMID- 14646457
TI  - [Acute respiratory distress syndrome].
AB  - Acute respiratory distress syndrome (ARDS) - is a life-threatening acute clinical
      syndrome of pulmonary insufficiency with high mortality. The causes of the
      syndrome are of every description - from crustacean poisoning to cardiopulmonary
      bypass. The rate of ARDS is not clear, because of diagnostical variety of ARDS
      and acute pulmonary dysfunction. The discussion on ARDS diagnostical criteria
      lasted for many years. The clinical criteria depend on how the essence of the
      disease is understood, on the size of lung infiltration, lung compliance and
      failure as well as degree of hypoxemia. The risk of ARDS increases with the
      increase of number of predisposing factors. The investigation data depend mainly
      on used datum-point for diagnostics of ARDS. It is obvious that non-cardiogenic
      light pulmonary edema is found very often, and serious lung lesions are rare
      enough. The aim of nowadays treatment is to cure the disease that causes the
      syndrome and to sustain vital functions. The early diagnostics of ARDS
      predisposing factors and minimization of their influence, the prevention, early
      diagnostics and timely treatment of complications are essential. In many cases
      ARDS caused by collateral factors is the constituent of multiple organ
      dysfunction syndrome. Anyway the ARDS predisposed by direct factors is often
      complicated by other organ (cardiovascular, renal, hepatic, hematogenous, central
      nervous system, gastrointestinal tract, etc.) dysfunction. In this case the
      treatment becomes more difficult and includes therapy correcting the function of
      other systems. In spite of intensive treatment, mortality of this syndrome still
      remains 50-90% according to the literature data. Though some authors state that
      recently the ARDS mortality decreased, but most of the authors did not notice any
      improvement during the last 20 years. The prognosis is determinated not only by
      pulmonary insufficiency itself (the cause of death in 5% of patients), but by the
      ARDS predisposing factor (the worst is sepsis and septic shock), multiple organ
      dysfunction syndrome, difficult physical state of the patient, sepsis as a cause
      or as a complication of ARDS, nosocomial pneumonia, progressive
      fibroproliferation in the lung. Considering the actuality of ARDS, the
      diagnostical criteria of ARDS, pathogenesis, clinical course and new treatment
      methods are reviewed in the publication.

PMID- 14646458
TI  - [Ventilator associated pneumonia: risk factors, diagnosis, treatment and
      prevention].
AB  - Treatment in the intensive care units has aggressive character. A lot of invasive
      diagnostic and treatment procedures are used in order to keep vital functions of
      the patients. Some complications are associated with treatment methods. Hospital
      acquired infections are the main cause of mortality. Since artificial lung
      ventilation is the most common invasive treatment method, ventilator-associated
      pneumonia is the most common hospital acquired infection. The development of
      hospital acquired infections is dependent on two independent pathophysiological
      factors: decreased patient immunity and colonization of patient cavities by
      bacteria. Ventilator-associated pneumonia causes almost half of intensive care
      units infections. The most etiologic organisms responsible for ventilator
      associated pneumonia in Europe and North America are Pseudomonas species and
      Methicillin resistant Staphylococcus aureus. Diagnosis of ventilator-associated
      pneumonia is based on clinical and laboratory criteria (fever, leukocytosis,
      purulent endotracheal secretions) and pulmonary infiltrates on chest radiograms.
      Pathogen can be distinguished using invasive or noninvasive techniques.
      Antimicrobial resistance aggravates treatment of ventilator-associated pneumonia.
      Antibiotic treatment should be chosen on the ground of clinical data, hospital
      epidemiologic situation and most common pathogens. Prevention of ventilator
      associated pneumonia is based on improving basic hygiene and nursing quality.
      Ventilator-associated pneumonia morbidity could be reduced by identification of
      risk factors and risk prevention.

PMID- 14646459
TI  - [Occupational therapy for patients after stroke].
AB  - After the stroke, person can lose efficiency due to prolonged recovery of
      biosocial dysfunctions. Occupational therapy is a purposeful activity employed on
      individuals with different dysfunctions like cognitive disorders, psychosocial
      dysfunctions, mental disability as well as learning or physical disability and
      other illnesses and states. It is aimed at reaching functional results for health
      improvement. Occupational therapy includes observation and evaluation of the
      patients, using tests, measures and evaluation of the received results. The
      evaluation of the efficiency of separate occupational therapy methods is
      inseparable part of multiple rehabilitation development.

PMID- 14646460
TI  - Prostate-specific antigen and transition zone index - powerful predictors for
      acute urinary retention in men with benign prostatic hyperplasia.
AB  - OBJECTIVES: To examine the efficacy of prostate-specific antigen and various
      parameters obtained by transrectal ultrasonography as predictors of acute urinary
      retention in patients with benign prostatic hyperplasia. METHODS: Eighty-nine men
      with symptoms of benign prostatic hyperplasia were enrolled in this study from
      February 2002 to June 2003. Among them, 21 patients presented with acute urinary
      retention. Transrectal ultrasonography was used to calculate the total prostate
      volume, transition zone volume and transition zone index. Sample of prostate
      specific antigen was taken in outpatient clinic or in clinic before first
      insertion of the catheter into the bladder, because of urinary retention. If the
      patient presented with inserted catheter, we used latest prostate-specific
      antigen date from the medical notes of outpatient clinic. To compare the
      usefulness of the various indexes, the area under the receiver-operator
      characteristic curve was calculated for each index. RESULTS: There were
      significant differences between patients with and without acute urinary retention
      in the total prostate volume (58.16 cm(3) and 44.28 cm(3), p=0.0028), transition
      zone volume (36.62 cm(3) and 23.70 cm(3), p=0.0001), transition zone index (0.62
      and 0.51, p=0.00022), prostate-specific antigen (4.96 ng/ml and 2.97 ng/ml,
      p=0.00069), age and quality of life score, but no significant difference in
      International Prostate Symptom Score. In patients with acute urinary retention,
      the area under the receiver-operator characteristic curve was 0.775 for
      transition zone index, 0.742 for prostate-specific antigen, 0.737 for transition
      zone volume, 0.696 for total prostate zone volume and 0.633 for International
      Prostate Symptom Score. CONCLUSIONS: The transition zone index and prostate
      specific antigen are accurate predictors of acute urinary retention in patients
      with benign prostatic hyperplasia and may be useful for deciding between surgical
      intervention and medical treatment.

PMID- 14646461
TI  - Staphylococcus aureus infection in the surgery of burns.
AB  - S. aureus causative agent is relatively pathogenic to humans and is found on the
      skin and mucosa of up to 40% of all population. Burn injuries are infected with
      S. aureus in 30% of cases; however, in many cases the injuries heal without the
      antibiotic therapy, solely by applying dressing with antiseptic solutions, early
      removal of necrotic masses and covering the injury with a skin graft. In 2000, in
      the Division of Plastic Surgery and Burns of our institution, the frequency of S.
      aureus infection among patients with burns was 47%, of which methicillin
      resistant S. aureus - 45%. The study included 100 patients who had S. aureus
      grown in the samples of their injuries. The article compares the severity of the
      trauma and the results of treatment in groups of patients with methicillin
      resistant S. aureus and methicillin-sensitive S. aureus.

PMID- 14646462
TI  - [Efficiency of arthroscopic treatment in the knee osteoarthritis].
AB  - THE AIM OF THE STUDY was to estimate the effectiveness of arthroscopic operations
      for patients suffering from knee osteoarthritis; to determine if it is possible
      to decrease pain, increase range of motions and mobility function. MATERIAL AND
      METHODS: The subjects of the study were patients with grade III and grade IV with
      knee osteoarthritis (Outerbridge classification), who underwent arthroscopic
      operations at Kaunas Red Cross Hospital in 1993-2000. They were followed after
      arthroscopic operations: debridement, partial synovectomy, meniscus resection and
      elimination of free bodies. Two hundred eighteen patients were examined by
      questionnaire; 137 (62.8%) were females and 81 (37.2%) were males. The age range
      was from 19 till 77 years (average 53.09 years). Follow-up was 1-8 years (average
      2.56 years). We estimated knee score and function score pre-op and 0.5 year, 1
      year, 3 years and more than 3 years post-op. RESULTS: Six months post-op 58.3% of
      patients were satisfied, 41.7% had no changes or even worsened. One year post-op
      77.5% of patients were satisfied; 3 years post-op 64 patients were followed,
      78.1% were satisfied; more than 3 years post-op 45 patients were followed, 82.2%
      were satisfied. The results six months post-op are as following: 33.9% very good,
      38.1% good, 22.9% satisfactory and 5.1% bad. One year post-op the very good and
      good results increased. Only 64 patients were followed-up three years post-op;
      64.1% had very good results and 25.0% had good results, satisfactory and bad
      results were in the range of 10.9%. The shorter time till arthroscopic
      intervention and performing arthroscopic debridement gave positive influence on
      good and very good results. Instability due to ACL rupture, big osteophytes,
      subchondral sclerosis, valgus deformation and grade III-IV patellofemoral
      cartilage changes gave worse results. Synovectomy had no influence on the
      results. CONCLUSIONS: Arthroscopy is a minimally invasive palliative intervention
      for the patients with the knee osteoarthritis.

PMID- 14646463
TI  - [Morphometric heart changes and left ventricular function in Duchenne's muscular
      dystrophy].
AB  - Heart lesion is characteristic in Duchenne's muscular dystrophy, however there is
      no unanimous opinion about its appearance time. OBJECTIVE: To evaluate early
      changes of the left ventricular morphometric parameters, systolic and diastolic
      function for the children with Duchenne's muscular dystrophy and to compare with
      the same age healthy children's data. MATERIAL AND METHODS: Eighteen patients
      with Duchenne's muscular dystrophy and 15 same age healthy boys were
      investigated. Mean age - 11 years. Echocardiography was performed in all cases.
      CONCLUSION: There were no changes of the left ventricular morphometric
      parameters, systolic and diastolic function observed in young age patients with
      Duchenne's muscular dystrophy.

PMID- 14646464
TI  - Low frequency fatigue of quadriceps muscle after sustained maximum voluntary
      contractions.
AB  - Immediately after sustained maximum voluntary contractions for 60 s, greater
      quadriceps muscle fatigue and, especially, low frequency fatigue is observed. The
      results of our study have shown that immediately after the exercise there was a
      significant (P<0.05) decrease in muscle force induced by low (20 Hz) and high (50
      Hz) stimulation frequencies and maximum voluntary contractions (it is not muscle
      length-dependent) and it did not recover to its initial (pre-exercise) level 15
      min after the end of exercise. These observations suggest the observed low
      frequency fatigue may consist of 2 phases: an early, rapid recovery phase (to 3
      min), likely related to muscle potentiation and metabolite build-up, and a slow
      recovery phase, which is not dependent on metabolite levels, but is especially
      dependent on muscle mechanical damage. There is an increase in low frequency
      fatigue during a slow recovery phase and it is more pronounced when low frequency
      fatigue is registered at short muscle length.

PMID- 14646465
TI  - [Investigations of poisonings with benzodiazepine derivatives mixtures by thin
      layer chromatography].
AB  - The thin-layer chromatography method was proposed for separation and
      identification of drugs in mixture alprazolam : brotizolam : clorazepate
      dipotassium. The mixture of these drugs excreted from body fluid (blood) was
      investigated by the thin-layer chromatography. Most acceptable is this mobile
      phase : benzene : dioxane : conc. ammonia : methanol : ethanol (60:25:5:10:10).
      Rf values for drugs: alprazolam 0.81-0.83, brotizolam 0.59-0.62, clorazepate
      dipotassium 0.67-0.69.

PMID- 14646466
TI  - Working conditions and health of the employees of public bus and trolleybus
      transport in Lithuania.
AB  - A questionnaire was used for investigation of 788 workers from three transport
      enterprises. The questionnaire was used for evaluation of occupational
      environment, lifestyle, psychosocial factors and self-evaluation of health. The
      most harmful occupational factors are unsatisfactory microclimatic conditions,
      diesel fuel, cooling oil, vibration, musculoskeletal load, and mental tension.
      Worker's lifestyle isn't healthy: 46% of them are smoking, 83% are drinking
      alcohol, 53% are physically inactive, 82% have bad nutrition regimen, 27% are
      everyday suffering from stressful situations. Main health impairments are
      musculoskeletal (46.2%), respiratory tract (22.2%), gastrointestinal (17.3%) and
      central nervous system (32.2%) diseases. Musculoskeletal disorders are
      statistically related to bad ergonomic work conditions, long workday hours, aged
      employees and long work experience of workers (p<0.05-0.002).

PMID- 14646468
TI  - [Kedainiai Hospital - one of the oldest hospitals in the region].
AB  - The review presents the facts of the origination of hospitals in Lithuanian
      villages based on historical documents. This process took place within the
      occupation period of czarist Russia. The recurrence of epidemics of grave
      infections diseases, such as cholera, typhus and diphtheria was one of the most
      important reasons leading to the establishment of network of rural health care
      institutions. Free outpatient and inpatient treatment of rural population was
      introduced for the first time, however this was accomplished not in all small
      towns. Kedainiai is a very old town with interesting and unique history. The
      article reviews development of health care in Kedainiai within the period of
      Kaunas Province.

PMID- 14646467
TI  - [Height, weight and body mass index of preterm very low birth weight infants at
      the preschool age].
AB  - THE AIM of this study was to reveal trends in height, weight, and body mass index
      of preterm very low birth weight children from birth up to 5 years of age.
      MATERIAL AND METHODS: The present study is based on cross-sectional growth study
      carried out in the Clinic of Neonatology of Kaunas University of Medicine. Total
      sample consisted of 735 children from birth up to 5 years of age: 379 preterm
      children with very low birth weight; and 356 term children with normal
      (appropriate for gestation age) birth weight. Height, weight, body mass index
      were measured. In order to verify if normal birth weight group corresponds to
      Lithuanian standards, the data of normal birth weight group children were
      compared with Lithuanian standard measures. Then data of very low birth weight
      group and normal birth weight group were compared. RESULTS: We found that height
      and weight of very low birth weight girls and boys were significantly lower than
      height and weight of term normal birth weight infant from birth up to 5 years of
      age (p<0.01). The body mass index of very low birth weight girls was
      significantly lower than that of term normal birth weight girls at birth (p<0.01)
      and at age of 4 years (p<0.05). The body mass index of very low birth weight boys
      was significantly lower than that of term normal birth weight boys at birth and
      from age of 2 up to the age of 5 years (p<0.01). These data show that very low
      birth weight boys differently from girls were more slender than term normal birth
      weight infant of the same age. CONCLUSIONS: It has been shown that preterm very
      low birth weight infants have different patterns of growth than term normal birth
      weight infants. The very low birth weight infants have not caught up on their
      retardation at the age of 5 years.

PMID- 14646469
TI  - [Sudden cardiac death by commotio cordis].
AB  - Commotio cordis due to blunt trauma to the precordium is a rare cause of death in
      young athletes, occurring less frequently than all of the other athletics-related
      deaths. Commotio cordis is a term used to describe cases of blunt thoracic impact
      causing fatality without structural damage of the heart and internal organs.
      Death is attributed to ventricular fibrillation, which is often resistant to
      resuscitative therapy. In this article we discussed this catastrophic event, its
      historical development, epidemiology and clinical presentation, mechanisms for
      sudden death in commotio cordis, limitations of evidence using animal models,
      autopsy findings, resuscitation and preventive measures.

PMID- 14646470
TI  - Apoptosis in non-proliferating cells: implications for viral infection and
      tumourigenesis.
AB  - To date much attention has been focused on regulation of apoptosis in
      proliferating cells. However, recent evidence shows that regulation of apoptosis
      in quiescent tissue plays an important role in homeostasis of the organism. This
      review examines the implications of apoptosis of quiescent cells for both
      tumourigenesis and viral infection such as HIV. In this article we propose a dual
      role for cellular activation in the homeostasis regulation. In this model
      cellular mitogens not only activate quiescent cells into the active cell cycle,
      but under certain conditions, loss of quiescence may result in apoptosis. The
      loss of quiescence-associated apoptosis may play a significant role in
      tumourigenesis and viral infections.

PMID- 14646471
TI  - Caspases in ischaemic brain injury and neurodegenerative disease.
AB  - The importance of caspases in developmental neuronal death is well-established.
      Recent data provide compelling evidence of caspase activation after ischaemic
      brain injury. Caspase inhibitors reduce cell death in several models of ischaemic
      injury. This review summarizes our current understanding of caspase function in
      ischaemic brain injury and examines the accumulating evidence of caspase
      participation in several neurodegenerative diseases. The therapeutic consequences
      of caspase inhibitor treatment in reducing cell death after such injury are also
      discussed.

PMID- 14646472
TI  - An investigation of a possible role for mitochondrial nuclease in apoptosis.
AB  - Since mitochondrial factors have been implicated in apoptosis, experiments were
      designed to assess whether or not the potent mitochondrial nuclease could be one
      of these factors. Nuclei isolated by two different methods were found to contain
      mitochondrial nuclease in masked form. This nuclease was released by treatment
      with the non-ionic detergent NP-40 and rendered trypsin-sensitive. It was not
      removed appreciably from the nuclei by washing and sedimentation of the nuclei
      through a sucrose cushion. Levels of the mitochondrial nuclease were followed
      during drug-induced apoptosis. Time courses of apoptosis in cultures of HL-60
      cells were monitored by flow cytometry of propidium iodide-stained cells and by
      agarose gel electrophoresis of extracted DNA. Changes in the inner mitochondrial
      transmembrane potential were monitored by flow cytometry of chloromethyl-X
      Rosamine-stained cells. Apoptosis was induced by treatment with either the
      chemotherapeutic agent etoposide (VP-16 at 10 microM) over an 8 h period or with
      the anti-rheumatic agent hydroxychloroquine (HCQ at 0.28 mM) over a 24 h period.
      These two drugs likely act in different pathways of apoptosis. VP-16 caused loss
      of the mitochondrial transmembrane potential 1.0-1.5 h before apoptosis was
      detected. On the other hand, treatment with HCQ caused these processes to occur
      in parallel possibly indicating that the mitochondrial changes are secondary
      events. No losses of masked mitochondrial nuclease were detected with either drug
      treatment during the course of apoptosis. HL-60 mitochondrial DNA was also not
      degraded during apoptosis induced by either agent. These observations likely
      explain why the mitochondrial DNA is not degraded and make it unlikely that
      mitochondrial nuclease plays any role in vivo in chromatin DNA fragmentation.

PMID- 14646473
TI  - Mesangial cell apoptosis induced by a fibronectin fragment.
AB  - We previously showed that in passive Heymann nephritis (PHN) rats, a large
      quantity of fibronectin (FN) fragments containing the central cell-binding (CCB)
      domain and adjacent domains are generated in the kidney and excreted into urine
      (Nishizawa et al., Biol Pharm Bull 1998; 21: 429-433). To ascertain whether the
      FN fragments could affect the progression of PHN, we investigated the effect of a
      150 K FN fragment containing the CCB and carboxyl-terminal heparin-binding (Hep
      2) domains on cultured rat mesangial cells. When rat mesangial cells cultured on
      FN-coated plates were exposed to the 150 K FN fragment, some mesangial cells
      detached from the FN substrate and then underwent apoptosis as judged by nuclear
      and DNA fragmentations. The 150 K FN fragment competitively inhibited the
      mesangial cell adhesion to the FN substrate in a dose-dependent manner.
      Furthermore, gelatinzymography of the conditioned medium of mesangial cells
      showed that the 150 K FN fragment induced and/or potentiated the extracellular
      matrix (ECM)-degrading proteinases including matrix metalloproteinases (MMPs) of
      mesangial cells. These results indicate that the 150 K FN fragment may elicit
      mesangial cell apoptosis by disrupting the mesangial cell adhesion through two
      distinct ways: the inhibition of mesangial cell adhesion and the ECM-degradation
      by the 150 K FN fragment-induced MMPs. Thus, FN fragments containing the CCB and
      adjacent domains generated in the kidneys of PHN rats may be involved in the
      evolution of the renal injury.

PMID- 14646474
TI  - Cleistanthin B causes G1 arrest and induces apoptosis in mammalian cells.
AB  - Cleistanthin B is a potential anticancer agent isolated from the tropical plant
      Cleistanthus collinus. We have previously shown that cleistanthin B is
      clastogenic and induces micronuclei formation and chromosomal aberrations. We now
      show that this compound inhibits DNA synthesis in Chinese hamster ovary (CHO)
      cells and induces apoptosis in cervical carcinoma (SiHa) cells. Flow cytometric
      analysis of cleistanthin treated CHO cells revealed that they were blocked in G1.
      Cervical carcinoma (SiHa) cells exposed to cleistanthin B shrank, rounded up and
      had condensed chromatin and fragmented nuclei. DNA isolated from cleistanthin
      treated cells exhibited the characteristic apoptotic ladder when electrophoresed
      in agarose gels. These results were confirmed by flow cytometry. Etoposide, a
      structurally similar compound also induced apoptosis in these cells although with
      a difference. Etoposide induced apoptosis after permitting cells to enter into S
      phase, while cleistanthin B stopped entry of cells into S phase and subsequently
      drove them to apoptosis.

PMID- 14646475
TI  - Two-dimensional gel analysis of apoptosis-specific p53 isoforms induced by 2
      methoxyestradiol in human lung cancer cells.
AB  - The natural metabolic byproduct of estradiol, 2-methoxyestradiol (2-MeOE2),
      induces apoptosis in human lung cancer cells by a p53-dependent mechanism. The
      expression of wild-type p53 isoforms was investigated in H1299 non-small cell
      lung carcinoma cells induced into apoptosis by 2-MeOE2. H1299 cells lack
      endogenous p53 and undergo predominantly a G1 arrest when infected with a
      recombinant wild-type p53 adenovirus. However, when H1299 cells transfected with
      p53 were treated with 2-MeOE2, they underwent rapid and extensive apoptosis.
      H1299 cells expressing mutant his273 p53 were unaffected by 2-MeOE2, indicating a
      dependence of 2-MeOE2-mediated apoptosis on the presence of a functional p53.
      Analysis of wild-type p53 phosphoisoforms in H1299 cells by two-dimensional gel
      electrophoresis revealed that 2-MeOE2 induced a unique group of acidic p53
      isoforms. Although most of the wild-type p53 in untreated H1299 cells migrated as
      at least five diffuse species with isoelectric points from pH 5.5-6.3, as many as
      nine additional forms migrating toward the acidic region with pI values from 4.4
      5.3 were detected in 2-MeOE2-treated apoptotic cells. Two other agents known to
      induce apoptosis, vinblastine and actinomycin D, induced a similar pattern of
      acidic p53 species as that observed for 2-MeOE2. The results indicated that the
      induction of apoptosis in H1299 cells by 2-MeOE2 is dependent on the upregulation
      of specific p53 isoforms. Identification of the specific p53 phosphoisoforms
      induced by MeOE2 will be an important step in understanding the regulation and
      function of p53 in apoptosis.

PMID- 14646476
TI  - Anti-Fas antibody-induced apoptosis in human colorectal carcinoma cell lines:
      role of the p53 gene.
AB  - The cell surface Fas antigen transducts an apoptotic signal by its crosslinking
      with Fas ligand or anti-Fas antibody in a variety of human cultured cells. In
      this study, we examined the expression of Fas antigen and its mediation of
      apoptosis in six human colorectal carcinoma cell lines. A flow cytometric
      analysis revealed that LoVo, DLD-1, WiDr and SW837 cell lines showed higher
      expression levels of Fas antigen, in contrast to lower expression in COLO201 and
      COLO320DM. Interferon-gamma enhanced the expression of Fas antigen in all of the
      cell lines examined. Both Fas ligand and Fas-associated phosphatase-1 (FAP-1)
      were expressed only in COLO320DM. Anti-Fas antibody induced apoptosis in LoVo
      carrying wild-type p53 gene, but not in the other five cell lines carrying
      mutated p53 gene. The transfection of wild-type p53 gene using an adenovirus
      vector upregulated P53 protein in WiDr and SW837 cells, both of which showed,
      however, no increase in apoptotic cells by anti-Fas antibody treatment. These
      results indicated that (1) Fas antigen was variably expressed, regardless of the
      p53 gene status and (2) the susceptibility to anti-Fas antibody-mediated
      apoptosis did not correlate to Fas, Fas ligand or FAP-1 expression levels.
      Therefore, we conclude that wild-type P53 expression might not necessarily be
      essential for Fas-mediated apoptosis in human colorectal carcinoma cell lines.

PMID- 14646477
TI  - Induction of apoptosis by gemcitabine in BG-1 human ovarian cancer cells compared
      with induction by staurosporine, paclitaxel and cisplatin.
AB  - A variety of chemotherapeutic agents induce cell death via apoptosis. We had
      shown previously that gemcitabine (2',2'-difluorodeoxycytidine) induced an
      atypical apoptosis in BG-1 human ovarian cancer cells; therefore, further studies
      were conducted to characterize more precisely gemcitabine-induced apoptosis in BG
      1 cells compared to a general inducer of apoptosis, staurosporine. BG-1 cells
      exposed to 0.5, 1.0 and 10 microM gemcitabine for 8 h, or staurosporine (1.0
      microM) for 6 h, exhibited high molecular weight DNA fragmentation (50 kbp);
      however, only staurosporine treatment produced internucleosomal DNA fragments
      (200 bp) in a laddered pattern on the agarose gel. Staurosporine (1.0 microM)
      rapidly induced phosphatidylserine plasma membrane translocation that increased
      linearly with time as measured by annexin V-FITC binding, and similar kinetics
      were observed for caspase activation by staurosporine in BG-1 cells. In contrast,
      10 microM gemcitabine increased phosphatidylserine expression in a small fraction
      of cells (5-10%) vs. untreated controls over the course of 48 h and significant
      caspase activity was detected within 12 h of drug exposure. Time-lapse video
      microscopy of BG-1 cells exposed to 1.0 microM staurosporine or 10 microM
      gemcitabine for up to 72 h showed that the morphologic changes and kinetics of
      cell death induced by these agents differed significantly. We also evaluated the
      apoptosis induced by paclitaxel (a mitotic poison) and cisplatin (an agent not
      dependent on cell cycle functions) in BG-1 cells by these methods because these
      drugs are used clinically to treat ovarian cancer. Our findings demonstrate that
      the kinetics of apoptotic cell death induced by gemcitabine and other
      chemotherapeutic agents should be taken into account when designing treatment
      strategies for ovarian cancer.

PMID- 14646478
TI  - Apoptosis in heart failure: a tale of heightened expectations, unfulfilled
      promises and broken hearts em leader.
AB  - Although apoptosis contributes significantly to remodeling of the fetal heart
      during evolution of cardiac chambers and correct routing of the great vessels, it
      has been believed that apoptosis does not occur in terminally differentiated
      adult cardiac muscle cells. However, apoptosis has recently been demonstrated in
      animal models of heart failure as well as in explanted hearts from patients with
      end-stage heart failure undergoing cardiac transplantation. Ventricular
      dilatation and neurohormonal activation, the hall-marks of heart failure, lead to
      upregulation of transcription factors, induce muscle cell hypertrophy and prepare
      cells for entry into the cell-division cycle. However, since terminally
      differentiated myocytes cannot divide, they die by apoptosis. It has been
      proposed that low-grade apoptosis in failing heart may be responsible for
      inexorable decline in left ventricular function. Better understanding of the
      molecular and cellular basis of apoptosis in the failing myocardium may lead to
      development of strategies aimed at preventing progressive myocyte loss and
      deterioration in left ventricular function.

PMID- 14646479
TI  - Signal transduction and the regulation of apoptosis: roles of ceramide.
AB  - Knowledge about the molecular regulators of apoptosis is rapidly expanding. Cell
      death signals emanating from death receptors or internal cell injury detectors
      launch a number of signaling pathways which converge on several key families of
      proteins including specialized proteases and endonucleases which play a critical
      role in the execution of the death order. In this review, we summarize recent
      discoveries relating to the signaling pathways involved, the death receptors, the
      caspase family of apoptotic proteases, Bcl-2 family members, the sphingolipid
      ceramide, and the tumor suppressor p53. In particular, we focus on the role
      played by ceramide as a coordinator of the stress response and as a candidate
      biostat in the detection of cell injury.

PMID- 14646480
TI  - ITAM motif in an apoptosis-receptor.
AB  - Signal transduction by the T-cell and B-cell antigen receptors and receptors for
      immunoglobulin Fc regions depends highly on the cytoplasmic immunoreceptor
      tyrosine-based activation motif (ITAM). After binding of the ligand,
      phosphorylation of the two conserved tyrosines of ITAM creates binding sites for
      downstream signalling molecules and thus enables the initiation of signalling
      events. Here, we report that the recently found apoptosis receptor, WSL-1/DR3/APO
      3/LARD/TRAMP also contains this motif. This may imply that the apoptosis receptor
      uses ways similar to immunoreceptors in relaying the induction/suppression of the
      apoptotic signal.

PMID- 14646481
TI  - Detection of apoptosis and phagocytosis in vitro in C6 rat glioma cells treated
      with tiazofurin.
AB  - Tiazofurin, an anticancer drug which inhibits IMP dehydrogenase activity and
      decreases GTP concentration in various malignant cells, induced inhibition of
      growth and apoptosis in C6 rat glioma in vitro. The effects of tiazofurin were
      significantly blocked by addition of exogenous guanosine, suggesting the role of
      decreased GTP in triggering specific signal transduction pathways involved in
      apoptosis of C6 cells. The most interesting result of this study was the evidence
      of phagocytosis of apoptotic cells in vitro by neighbouring cells, a phenomenon
      considered to occur only in apoptosis in vivo. The possibility of observing
      phagocytosis in C6 glioma cells suggests that this cell system could be a good
      model for studying mechanisms of phagocytosis in vitro.

PMID- 14646482
TI  - Differentiation and apoptosis without DNA fragmentation in cultured Schwann cells
      derived from wallerian-degenerated nerve.
AB  - The Schwann cell cables provide particularly favorable sites for the growth of
      regenerating axonal sprouts. However, if they remain denervated, endoneurial
      fibrosis takes place with the Schwann cells atrophying and total Schwann cell
      number gradually decrease with time. Even when regenerating axonal sprouts invade
      into the cables, Schwann cells do not survive for long periods if they fail to
      make axonal contact. These observations strongly suggest the involvement of
      apoptosis in peripheral nerve degeneration and regeneration. So, we investigated
      the behavior of Schwann cells prepared from wallerian-degenerated adult rat
      sciatic nerve in vitro. The secondary cultured Schwann cells showed serial
      changes in morphology, mitotic activity and migratory activity as they do during
      Schwann cell cable formation in vivo. At the final stage of differentiation, the
      Schwann cells became rounded and detached from the flask with extensive blebbing.
      Electron micrographs clearly demonstrated typical cytoplasmic changes of
      apoptosis, but, nuclei of most of the cells retained their size and morphology
      with residual nucleolar structures. An agarose gel electrophoresis of DNA clearly
      demonstrated that there was not any DNA fragmentation up to 120 h after
      detachment. Results by in situ apoptosis detection assay did not show any DNA
      degradation despite the substantial decrease in Schwann cell number. In
      conclusion, during peripheral nerve degeneration and regeneration, supernumerary
      Schwann cells are removed by apoptosis, however, it lacks most of the nuclear
      events of usual apoptosis.

PMID- 14646483
TI  - Cytokine-induced production of NO by macrophages induces apoptosis and
      immunological rejection of AK-5 histiocytic tumor.
AB  - The immunological rejection of the AK-5 histiocytoma in syngeneic hosts involves
      the participation of NK cells and the upregulation of Th1 type cytokine response.
      The tumor cells are killed by necrosis and apoptosis. We have studied the role of
      host peritoneal macrophages in tumor regression. Activated macrophages from tumor
      bearing animals produce cytokines like IL-1 beta, TNF-alpha, IL-12 and free
      radicals like nitric oxide during tumor regression. IL-12 and IFN-gamma played a
      crucial role in the induction of NO production by the host macrophages, since
      administration of anti IL-12 and anti IFN-gamma antibodies in AK-5 tumor-bearing
      animals suppressed NO production by the macrophages. Similarly the cytotoxic
      activity of the host macrophages which is dependent on NO production was also
      affected in antibody injected animals. These studies indicate an important role
      for cytokines in the activation of host macrophages which in turn produce nitric
      oxide that is involved in the induction of apoptosis in AK-5 cells, leading to
      the regression of the tumor.

PMID- 14646484
TI  - Critical parameters influencing hyperthermia-induced apoptosis in human lymphoid
      cell lines.
AB  - Brief mild hyperthermia is sufficient to induce apoptosis (programmed cell death)
      in many cell lines. Here we describe the effects of a number of factors
      modulating heat shock induced apoptosis outcomes. We report the effects of cell
      type, heat load, recovery times, cellular growth phase, and protein synthesis on
      the levels of apoptoses seen in heat stressed cell populations. We observe that a
      number of cell lines are competent to undergo heat stress induced apoptosis using
      both the comet assay and cellular and nuclear morphologies. Of the cell lines
      tested we saw a wide spectrum of sensitivities, ranging from resistant (less than
      1% apoptotic after 12 h) to exquisitely sensitive (>95%). By incrementally
      increasing the heat load from 37-49 degrees C, we observed a gradual increase in
      apoptosis with a significant change from apoptotic to necrotic death at
      temperatures beyond 45 degrees C. The kinetics of the apoptotic response to heat
      shock were also examined. A time dependent increase in apoptotic cell death was
      seen after initial hyperthermic treatment with most cell types reaching a
      'plateau' at 18 h. In addition to these parameters we report that growth phase
      has a strong influence on the number of apoptoses induced as a result of heat
      stress. Cultured cells, grown to a plateau, undergo apoptosis at a much higher
      level than similarly treated cells taken during an exponential phase of growth.
      Finally, we determined the necessity of protein synthesis for apoptotic
      competency.

PMID- 14646485
TI  - Transgenic mice in apoptosis research.
AB  - Transgenic mice have proved to be a valuable tool in various aspects of apoptosis
      research. They are particularly useful for studying apoptosis-related gene
      products in primary cells which may lead to different effects from similar
      experiments using immortalized cell lines. They allow the impact of these gene
      products on multi-faceted physiological processes to be identified. Transgenic
      mice have been generated expressing molecules ranging from Bcl-2 and Bcl-2 family
      members to CD95, superoxide dismutase and rhodopsin. This review details some of
      the insights revealed from such studies in diverse areas ranging from lymphoid
      development to neurodegeneration and effects on intracellular signalling.

PMID- 14646486
TI  - Fanconi anaemia syndrome and apoptosis: state of the art.
AB  - Fanconi anemia (FA) is a rare recessive, human genetic syndrome characterized by
      progressive bone marrow failure, developmental abnormalities, predisposition to
      malignancy, chromosomal instability and DNA damage hypersensitivity. Two (FAA and
      FAC) of the five genes involved were cloned but their functions remain unknown.
      At present, the involvement of FA proteins in DNA repair, redox status of the
      cell and apoptosis are areas of intensive investigation. The aim of this review
      is to synthesize current results and ideas concerning the involvement of
      apoptosis in the FA phenotype and conversely, the role of FA proteins in the
      control of apoptosis.

PMID- 14646487
TI  - Biological significance and molecular mechanisms of p53-induced apoptosis.
AB  - The recognition that the p53 tumour suppressor gene is frequently inactivated in
      human cancers has galvanized an intense pursuit of the fundamental mechanisms by
      which the encoded protein halts malignant transformation and tumour progression.
      It is now evident that p53 is a multifunctional transcription factor that is
      intimately involved in the cellular response to stressful stimuli such as DNA
      damage and hypoxia. In addition to its role in the surveillance mechanisms that
      arrest cell cycle progression, p53 can also trigger apoptosis in response to DNA
      damage or oncogenic aberrations that induce aberrant cell cycle progression.
      Since p53 is a critical component for DNA damage-induced apoptosis, the frequent
      occurrence of p53 mutations in human neoplasia provides a genetic basis for their
      poor response to genotoxic anticancer agents. Two recent studies offer key
      insights into the molecular mechanisms employed by p53 to induce cell death. One
      model indicates that p53 induces redox-related genes that generate reactive
      oxygen species and promote the oxidative degradation of mitochondrial components.
      The other demonstrates p53-mediated induction of DR5, a death receptor of the
      tumour necrosis factor receptor family, that induces death by caspase-mediated
      proteolysis. These insights provide an exhilarating array of possible therapeutic
      interventions against p53-deficient human cancers that may pay enormous dividends
      in the not-too-distant future.

PMID- 14646488
TI  - Establishment of a mutant from human monocytic leukaemia U937 that exhibits a
      genetically dominant resistance to TNF alpha-induced apoptosis.
AB  - Tumour necrosis factor-alpha (TNF alpha) is a cytokine that induces apoptosis in
      various cell systems by binding to a TNF receptor (TNFR). To study TNF alpha
      induced apoptosis, we isolated and characterized a novel TNF alpha resistant
      variant, U937/TNF clone II-5, from human monocytic leukaemia U937 cells. The II-5
      cells resist apoptosis by TNF alpha and anti-Fas antibody but not by anticancer
      drugs, such as VP-16 and Ara-C. Somatic cell hybridization between U937 and II-5
      showed that the apoptosis resistance to TNF alpha in II-5 was genetically
      dominant. This dominant mutation in II-5 cells blocks TNF alpha-induced
      disruption of mitochondrial membrane potential and caspase-3 activation.
      Expression of TNFR, Fas and Bcl-2 family proteins were not changed in II-5 cells.
      These results suggest that the apoptosis-resistant II-5 cells could have a
      functional defect in apoptosis signalling from TNFR to mitochondria and caspase
      activation. The II-5 cells could be useful in studying the signalling linkage
      between TNFR and mitochondria.

PMID- 14646489
TI  - Induction of apoptosis in proliferating lymphocytes by tricyclic antidepressants.
AB  - We have previously found that tricyclic antidepressants (TCAs) induce apoptosis
      in quiescent human lymphocytes. The aim of the present study was to evaluate if
      TCAs induce apoptosis in proliferating human lymphocytes and in established
      blastoid lymphocytes also. The development of conA-induced lymphoblast
      populations was followed by measuring the CD25 membrane expression. Three TCA
      compounds were run with the following concentrations: imipramine (10, 20, 30, 40,
      60 microM), clomipramine (1, 10, 20, 30, 40 microM) and citalopram (40, 60, 80,
      100, 180 microM). They all induced a dose-dependent apoptosis both in
      continuously transformed, as well as in established lymphoblasts. Preincubation
      of the TCA up to 48 h did not significantly increase induction of apoptosis. The
      three drugs tested were found to be potent inducers of apoptosis in proliferating
      lymphocytes. Furthermore, we found that the apoptotic populations in
      proliferating and in established blastoid lymphocytes were of fairly the same
      magnitude than in the corresponding population in TCA-incubated resting
      lymphocytes. In conclusion, we demonstrate that TCAs induce apoptosis in
      proliferating lymphocytes, as they do in quiescent lymphocytes. Furthermore, the
      extent of apoptosis was even more pronounced in TCA-incubated lymphoblasts
      compared to TCA-treated resting lymphocytes.

PMID- 14646490
TI  - Increased numbers of alveolar macrophages with apoptotic bodies predict lung
      carcinoma.
AB  - In our previous study on fixed tissue blocks, we reported a high apoptotic rate
      in patients with operated small cell lung carcinomas. In addition to tumour
      cells, numerous apoptotic bodies could also be found within alveolar macrophages
      within and close to tumour tissue. In order to test if such cells could be found
      in sputum smears and if their presence could be utilized as a marker in tumour
      diagnosis, we analyzed the occurrence of alveolar macrophages with apoptotic
      bodies (AMWABs) in a set of sputum smear and BAL samples from patients with and
      without a pulmonary malignancy. An increased amount of AMWABs in the cytoplasm
      could be found in sputum and BAL samples from patients with lung cancer.
      Interestingly, AMWABs could also be seen in patients with a histologically
      confirmed pulmonary malignancy, but with no detectable tumour cells in their
      sputum smear. Thus, the presence AMWABs in sputum smears could serve as a more
      sensitive marker of pulmonary malignancy than the presence of malignant cells per
      se. This is the first report describing apoptotic bodies in macrophages and the
      utility of their detection in cancer diagnosis.

PMID- 14646491
TI  - Induction of apoptosis in the centre of multicellular tumour spheroids of
      colorectal adenocarcinomas--involvement of CD95 pathway and differentiation.
AB  - Multicellular tumour spheroids (MCTS) are three-dimensional cell culture systems
      which are widely used in cancer research. They are characterized by an outer zone
      of proliferating cells, an inner region of differentiating quiescent cells and an
      area of so-called necrotic cell death in their centre. The exact cause of this
      cell death, a controversy for many years, was the aim of the present study. Our
      data show that cell death in the centre of MCTS of three colorectal
      adenocarcinoma cell lines (HRT-18, HT-29 and CX-2) was induced by apoptosis.
      Apoptotic cells were initially distributed at random but accumulated very quickly
      in the quiescent and central area at day 4-5, suggesting a time- rather than size
      dependent synchronization of apoptosis parallel to the formation of the
      proliferation gradient in MCTS. To study mechanisms inducing apoptosis, the Fas
      pathway was investigated. A cell-cell contact-dependent expression of CD95 was
      found in all MCTS. FasL was not detected in monolayer cultures, but was expressed
      in spheroids of HRT-18 and CX-2. We found that TNF alpha and TGF beta 1 activated
      the CD95 pathway in all three cell lines. Since both TNF-alpha and TGF-beta are
      known to be inducible by hypoxia in a variety of cell types, we suggest that
      these hypoxia-induced factors sensitize the CD95 pathway in the quiescent area of
      MCTS. Furthermore, a loss of the heat shock proteins 27, 32, 60, 73 and 90 was
      observed in the quiescent area of spheroids. This suggests that tumour cell
      differentiation in the inner region of MCTS may be an additional factor inducing
      apoptosis.

PMID- 14646492
TI  - Heat-induced testicular apoptosis occurs independently of hormonal depletion.
AB  - Previous studies have demonstrated that testicular germ cell apoptosis can be
      induced both by heat stress and by withdrawal of androgens and gonadotrophins. To
      investigate whether heat-induced germ cell apoptosis occurs independently of the
      altered levels of hormones that occur with heat exposure, mouse testicular
      apoptosis was studied using an in vitro system with controlled levels of
      testosterone, FSH and LH. It was observed that cells underwent apoptosis sooner
      in the absence of hormones at the same temperature. Apoptosis also occurred
      earlier at abdominal temperature compared to scrotal temperature with the same
      hormonal levels. No somatic tissues studied underwent apoptosis at 37 degrees C
      under the same culture conditions. These results suggest that heat stress may
      independently activate an apoptotic pathway in the testis, and that hormone
      deprivation may induce apoptosis via a separate mechanism.

PMID- 14646493
TI  - The p75 neurotrophin receptor: effects on neuron survival in vitro and
      interaction with death domain-containing adaptor proteins.
AB  - The p75 neurotrophin receptor (p75NTR) is a death domain (DD) containing receptor
      of the TNF/FAS(APO-1) family. p75NTR has recently been shown to mediate apoptosis
      in certain types of neurons as well as in oligodendrocytes. The molecular
      mechanisms by which p75NTR stimulates apoptosis are still unknown. Here, we have
      tested whether overexpression of p75NTR could modulate survival of sympathetic
      neurons cultured in the presence or absence of NGF. Moreover, using the yeast two
      hybrid system, we tested whether p75NTR intracellular domain was able to dimerize
      or interact with known DD-containing proteins including FADD, RIP, RAIDD and
      TRADD. We found that over-expression of p75NTR had no effect on the survival of
      sympathetic neurons cultured in the presence of NGF but instead delayed neuronal
      death following NGF deprivation. These results strongly support the finding that
      p75NTR is not involved in the apoptosis process induced by NGF deprivation in
      sympathetic neurons. We also foun d that the intracellular domain of p75NTR
      failed to associate either with itself or with other known DD-containing
      proteins. This suggests that the mechanisms by which p75NTR triggers apoptosis in
      certain cell types are different from those used by other receptors of the
      TNF/FAS family.

PMID- 14646494
TI  - Antiapoptotic action of prolactin is associated with up-regulation of Bcl-2 and
      down-regulation of Bax in HC11 mouse mammary epithelial cells.
AB  - The effect of prolactin on apoptosis and the expression of bcl-2 and bax in HC11
      mouse mammary epithelial cells were investigated. Flow cytometric analysis of Bcl
      2 level (FITC-conjugated monoclonal anti-Bcl-2 antibody and FITC-conjugated
      monoclonal anti-IgG1 antibody as a negative control), number of apoptotic cells
      and cell cycle phases (DNA stained with DAPI) was performed. Bax transcript was
      measured using the RT-PCR method with GAPDH serving as a reference gene.
      Administration of prolactin (5 microg/ml) in the presence of insulin stimulated
      differentiation of mammary epithelial cells, which manifested in stopping cells
      at G0/G1 phase, cell swelling and increase of cell number with enhanced protein
      content. Moreover, prolactin highly significantly reduced the extent of apoptosis
      of HC11 cells during 48 h of incubation. Nevertheless, the apoptotic cell number
      rose with increased time length of cell culture, probably due to the resulting
      high cell density and EGF withdrawal from t he incubation medium. The
      antiapoptotic effect of prolactin was associated with up-regulation of bcl-2
      expression, shown as an increase in cell numbers expressing this protooncogene
      and elevated Bcl-2 content in these cells. A negative relationship (r=-0.87, p<
      or =0.001) between the number of apoptotic cells and those expressing bcl-2 was
      also found. Prolactin administration lowered Bax transcript by 68.8% and 70.7%
      after 3 and 6h, respectively. In conclusion, the results presented indicate that
      stimulation of bcl-2 expression with simultaneous suppression of bax may be key
      events in the mechanism of antiapoptotic action of prolactin in HC11 mammary
      epithelial cells.

PMID- 14646495
TI  - Purification and characterization of a DNase gamma-like endonuclease from Xenopus
      laevis liver.
AB  - We recently found that two apoptotic DNase gamma-like endonucleases (36 and 38
      kDa DNases) were present in Xenopus laevis larval and adult liver cell nuclei and
      that their activities increased in metamorphic climax. Here, we purified the main
      DNase gamma-like endonuclease from Xenopus laevis liver cell nuclei and
      characterized its physical and enzymatic properties in detail. The molecular mass
      of Xenopus liver nuclear endonuclease was 38,000 daltons as determined by SDS
      polyacrylamide gel electrophoresis. A native molecular mass of 35,000 was
      estimated by gel filtration. The purified Xenopus liver endonuclease was a
      neutral one and required both Ca2+ and Mg2+ for DNase activity. Unlike the
      mammalian DNase gamma, the Ca2+/Mg2+ requirement could not be supplied by Mn2+.
      The inhibition profiles by aurintricarboxylic acid, sodium citrate and divalent
      metal ions such as Co2+, Ni2+, Cu2+ and Zn2+ were similar to those of mammalian
      DNase gamma. These results suggest that this endonuclease is a Xenopus laevis
      homolog of the mammalian apoptotic endonuclease DNase gamma.

PMID- 14646496
TI  - Alpha 1-antichymotrypsin inhibits chymotrypsin-induced apoptosis in rat hepatoma
      cells.
AB  - Increased serum levels of alpha1-antichymotrypsin (alpha 1ACT) are observed in
      some cancer patients, especially those with hepatocellular carcinoma. A possible
      role of alpha 1ACT in tumour growth has been suggested, but this remains
      uncertain. We have demonstrated that alpha 1ACT inhibited chymotrypsin-induced
      apoptosis in rat hepatoma H4 cells. Even low concentrations of chymotrypsin (but
      not trypsin) induce apoptosis in H4 cells with a minimum effective concentration
      of 2.4 x 10(-2) units/ml (0.5 microg/ml), and this apoptosis was inhibited by
      alpha 1ACT in a concentration-dependent manner. Furthermore, the concentrations
      of alpha 1ACT required to inhibit the apoptosis were lower than normal serum
      levels. These results may indicate that alpha 1ACT plays a role in the apoptosis
      of rat hepatoma cells.

PMID- 14646497
TI  - Elevated cytokeratin-19 expression associated with apoptotic resistance and
      malignant progression of human cervical carcinoma.
AB  - Cytokeratin-19 is an intermediate filament protein associated with the integrity
      of cell structure, and its elevated expression has been reported to correlate
      with the disease progression of oesophagus and lung cancers. In this study, we
      examined the level of cytokeratin-19 in five cervical cancer cell lines by
      immunobinding and Western blotting analyses. Compared with two control cell
      lines, FS-4 (foreskin cell line) and G9T (glioma cell line), all five cervical
      carcinoma cell lines (Caski, CC7T, ME180, HeLa and SIHA) showed higher
      cytokeratin-19 expression. By double-staining flow cytometry, expression of
      cytokeratin-19 in cervical cancer cells was suggested to be in a cell cycle
      independent manner. Furthermore, we could specifically localize the SIHA cell
      derived tumours in nude mice by injecting with cytokeratin-19-recognized
      radiolabelled MAb Cx-99 antibody, suggesting the possibility of using cytokeratin
      19 as a marker of cervical carcinoma. A clinical investigation was therefore
      performed on 19 patients (11 patients with cervical carcinoma and eight patients
      with benign neoplasia). In the 11 patients having cervical carcinoma, all eight
      patients with advanced stages and one out of three patients with early stage
      diseases showed higher cytokeratin-19 protein contents than the other 10 patients
      with benign neoplasia. This suggested that elevation of cytokeratin-19 level was
      associated with cervical cancer staging. In addition, we have studied the
      biological significance of elevated cytokeratin-19 level in malignant cervical
      cancer. The apoptotic rate of cervical carcinoma cells in response to cisplatin
      was increased if their cellular cytokeratin-19 level was reduced by specific
      antibody MAb Cx-99. These results indicated that elevation of cytokeratin-19
      expression could associate with the apoptotic resistance and malignant
      progression of cervical carcinoma.

PMID- 14646498
TI  - Differential inducibilities of GFAP expression, cytostasis and apoptosis in
      primary cultures of human astrocytic tumours.
AB  - Glial fibrillary acidic protein (GFAP) is an astrocytic lineage-specific
      intermediate filament protein, and its expression or non-expression is inversely
      correlated with the tumourigenecity of astrocytoma cells. To estimate the GFAP
      levels of astrocytes in intracranial tumour tissues, we established primary
      cultures from six astrocytic tumour specimens and used a double-staining flow
      cytometric method to detect the different levels of GFAP among these primary
      cultures. Although these primary cultures exhibited the same Matrigel
      invasiveness, their GFAP expression is inversely related to the rate of cell
      growth and the histologic grade of the original tumour. Phenylacetate, 12-O
      tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate, which are potent
      inducers of differentiation in various cancer cells, have been examined for their
      effects on these primary cultures. Cytostasis was more or less caused by these
      compounds in all six primary cultures, but induction of GFAP was observed only in
      the primary culture derived from a less malignant astrocytoma specimen having the
      highest intrinsic GFAP level. Interestingly, this primary culture, but not
      others, also exhibited increased HRG-alpha expression after phenylacetate or
      sodium butyrate treatment. Loss of the inducibility of differentiation-related
      gene expression could be one of the events involved in the malignant progression
      of astrocytomas. In addition, the chemotherapeutic agent BiCNU has a killing
      effect on all six primary culture cells, with LD50 less than 60 nM. The
      underlying mechanism was through the induction of apoptosis in these primary
      culture cells regardless of their varying malignancies of original tumours.
      However, unlike colon cancer and leukaemia cells, sodium butyrate could not
      induce apoptosis within 4 days in these astrocytic tumour cells, indicating that
      the cell context of different cell types indeed determined the ability of sodium
      butyrate to induce apoptosis.

PMID- 14646499
TI  - Dipropylcyclopentylxanthine triggers apoptosis in cells from patients with
      myeloid leukaemia.
AB  - 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), a xanthine analogue used as a
      selective antagonist of adenosine receptors, caused apoptosis in a variety of
      leukaemia-derived cell lines as well as in cells from patients with myeloid
      leukaemia. Apoptosis was assessed by flow cytometry, by DNA fragmentation and by
      accumulation of histones, H2A, H2B, R3 and H4, in the nucleoplasm of cells. Cell
      cycle analysis indicated that apoptosis occurred irrespective of the cell cycle
      phase. DPCPX did not trigger apoptosis in resting human peripheral blood
      lymphocytes; neither did it potentiate the apoptotic effect of phytohemagglutinin
      (PHA), when these cells were activated by PHA. These results indicate that DPCPX
      may be useful in the therapy of proliferative disorders of the hematopoietic
      system.

PMID- 14646500
TI  - Delivery of cytotoxic drugs from carrier cells to tumour cells by apoptosis.
AB  - A new drug delivery approach, apoptotic-induced drug delivery (AIDD), is
      presented that is based on apoptosis as a mechanism to trigger delivery of drugs
      from carrier cells. It was investigated whether apoptotic drug-loaded carrier
      cells could deliver drugs to tumour cells by various mechanisms, including drug
      release through a more permeable apoptotic cell membrane, and by phagocytosis of
      drug-loaded apoptotic cells by tumour cells. The feasibility of this novel
      concept was evaluated in an in vitro carrier cell model that consisted of S49
      mouse lymphoma cells that apoptose upon exposure to dexamethasone (DX). Membrane
      permeability was evaluated by measurement of release of a fluorescent dye
      (calcein-AM, C-AM) from C-AM-loaded S49 cells. Phagocytotsis of fluorescent PKH
      26-labeled S49 cells was determined in co-culture studies with rat glioma (RG-2)
      cells using fluorescence microscopy and flow cytometry. Cytotoxicity of RG-2
      cells due to temozolomide (TMZ)-loaded S49 cells was evaluated by a colony
      formation assay following co-culture of these cells for up to 8h. Calcein release
      from S49 cells was enhanced by approximately 30% at 48 h following treatment with
      DX compared to control S49 cells. Based on both flow cytometric and microscopic
      analyses, RG2 phagocytized apoptotic S49 cells to a four- to sevenfold greater
      extent than control S49 cells at co-incubation times from 4-48 h. The TMZ-loaded
      apoptotic S49 cells caused the largest degree of toxicity, about 50% cell kill,
      whereas TMZ-loaded control S49 caused 30% cell kill. The preliminary data suggest
      that AIDD should be further explored.

PMID- 14646501
TI  - Crocidolite asbestos causes an induction of p53 and apoptosis in cultured A-549
      lung carcinoma cells.
AB  - A number of genotoxic chemicals and agents, such as benzo(a)pyrene and
      ultraviolet light, are able to induce nuclear accumulation of p53 protein.
      Usually, this response is transient and a consequence of stabilization of the
      wild-type p53 protein. After withdrawal of the exposure, the amount of p53
      protein returns to a normal level within hours or a few days. We have studied the
      p53 response to the exposure of crocidolite asbestos in A-549 lung carcinoma
      cells using three different methods, i.e., p53 immunohistochemistry, Western
      blotting and metabolic labelling followed by p53 immunoprecipitation. With these
      techniques we demonstrate a dose-dependent p53 nuclear response to crocidolite
      exposure. The half-life of p53 protein in A-549 lung carcinoma cells cultured in
      serum-free media increased from 30 up to 80 min, and the protein reacted with a
      wild-type specific antibody suggesting that it was in a wild-type conformation.
      In situ 3'-end labelling of A-549 cells demonstrated a dose-dependent increase in
      apoptotic activity. Our data support the idea that increased apoptotic activity,
      induced by crocidolite, is mediated by p53.

PMID- 14646502
TI  - Apoptosis mediated by a novel leucine zipper protein Par-4.
AB  - The prostate apoptosis response-4 (par-4) gene was isolated in a differential
      screen for immediate-early genes that are up-regulated during apoptosis of
      prostate cancer cells. Unlike most other immediate-early genes, par-4 is
      exclusively induced during apoptosis. The expression or induction of par-4 is not
      restricted to prostatic cells. The par-4 gene is widely expressed in diverse
      normal tissues and cell types and conserved during evolution. Par-4 protein
      contains a leucine zipper domain that is essential for sensitization of cells to
      apoptosis. Functional studies indicate that par-4 expression is necessary to
      induce apoptosis. Par-4 protein may induce apoptosis by a p53-independent pathway
      that involves cytoplasmic inactivation of atypical protein kinase C isoforms
      resulting in down-regulation of MAP kinase activity and an up-regulation of p38
      kinase activity. However, Par-4 is detected in the cytoplasm and in the nucleus,
      suggesting both cytoplasmic and nuclear roles for the pro-apoptotic protein.
      Interestingly, Par-4 is predicted to contain a death domain homologous to that of
      Fas or TRADD, and may therefore trigger a death cascade analogous to that of the
      death domain proteins. Par-4-dependent apoptosis is abrogated by Bcl-2 and by
      caspase inhibitors. Identification of the components of the p53-independent
      apoptosis pathway induced by Par-4 may help to further elucidate the mechanism of
      Par-4 action. Moreover, in view of the pro-apoptotic function of Par-4, its role
      in diseases, such as cancer and neurogenerative disorders, whose pathophysiology
      involves apoptotic cell death needs further investigation.

PMID- 14646503
TI  - Bcl-2 antisense therapy for cancer: the art of persuading tumour cells to commit
      suicide.
AB  - The Bcl-2 oncoprotein is a potent inhibitor of apoptosis induced by numerous
      physiological and pathological stimuli, and uncontrolled cell survival due to Bcl
      2 overexpression has been shown to contribute to tumour formation and the
      development of autoimmune diseases. The multifunctional action of Bcl-2 is
      thought to prevent activation of the ced3/caspase-3 subfamily of ICE proteases,
      resulting in suppression of the death effector machinery. Since most conventional
      anti-cancer agents act by triggering this suicide pathway, overexpression of Bcl
      2 in cancer cells has also been associated with drug resistance. The antisense
      approach to inhibition of gene expression relies on the binding of small
      synthetic oligodeoxynucleotides to a complementary base sequence on a target
      mRNA. As a consequence, expression of the corresponding gene is downregulated due
      to endonuclease-mediated hydrolysis of the mRNA strand, or to translational
      arrest arising from sterie hindrance by the RNA:DNA heterodimer. Since these
      mechanisms of action differ from those exerted by conventional anticancer agents,
      antisense oligodeoxynucleotides designed to specifically inhibit bcl-2 gene
      expression hold great promise as agents that could overcome clinical drug
      resistance, and improve the treatment outcome of many hitherto incurable cancer
      diseases.

PMID- 14646504
TI  - Mutation of BCL-2 Family Proteins in Cancer.
AB  - Apoptosis is a genetically controlled cell death process that is required for
      normal development and tissue homeostasis. Suppression of apoptosis can confer a
      growth advantage to cells and contribute to cancer; many cancers are relatively
      resistant to apoptosis, including that induced by radiation or chemotherapeutics.
      Mutations which inactivate pro-apoptotic or activate anti-apoptotic proteins in
      cancer cells are therefore likely to be responsible for some of these
      differences. BCL-2 family proteins are key regulators of apoptosis and there is
      evidence supporting a role for mutation of BCL-2 family proteins in cancer. This
      includes well established events such as activation of BCL-2 via translocations
      in follicular lymphoma, as well as more recent observations implicating
      activation of Bcl-X(L) expression and frameshift and missense mutations of BAX
      and BCL-2 in cancer.

PMID- 14646505
TI  - The TRAIL of Death.
AB  - The TNF ligand family member termed TRAIL has been shown to induce apoptosis in a
      wide variety of transformed cell lines. The normal functions of this cytokine in
      vivo remain, however, relatively unknown. The complexity of this biological
      system has now increased unexpectedly with the identification of four distinct
      receptors for TRAIL, two of which have cytoplasmic death domains. This review
      will describe the known biological effects of TRAIL, as well as the structure and
      possible functions of its recently identified receptors.

PMID- 14646506
TI  - cDNA cloning of human DNase gamma: chromosomal localization of its gene and
      enzymatic properties of recombinant protein.
AB  - We report here on the nucleotide sequence of the cDNA encoding human DNase gamma,
      which is a candidate for an apoptotic endonuclease. The cDNA clone isolated from
      a human spleen cDNA library is composed of a 918 bp open reading frame encoding a
      305 amino acid precursor protein for DNase gamma. Northern blot analysis reveals
      that the expression of a single transcript of 1.5 kb DNase gamma mRNA is detected
      in the spleen and liver. The chromosomal localization of DNase gamma gene is
      mapped to chromosome 3 at region p21.1-p14.2 by fluorescence in situ
      hybridization (FISH). Characterization of thioredoxin-DNase gamma fusion protein
      (Trx-hDNase gamma) shows that the recombinant protein has a Ca(2+)/Mg(2+)- or
      Mn(2+)-dependent endonuclease activity that cleaves chromatin DNA to nucleosomal
      units. The optimum pH is around 7.2. Zn(2+) and aurintricarboxylic acid (ATA)
      inhibits the activity in dose-dependent manners. These properties are identical
      to those of purified DNase gamma.

PMID- 14646507
TI  - Presence of DNase gamma-like endonuclease in nuclei of neuronal differentiated
      PC12 cells.
AB  - DNase gamma, which cleaves chromosomal DNA into nucleosomal units (DNA ladder
      formation), has been suggested to be the critical component of apoptotic
      machinery. Using rat pheochromocytoma PC12 cells, which are differentiated to
      sympathetic neurons by nerve growth factor (NGF), we investigated whether DNase
      gamma-like enzyme is present in neuronal cells and is involved in neuronal cell
      death. The nuclear auto-digestion assay for DNase catalyzing internucleosomal DNA
      cleavage revealed that nuclei from neuronal differentiated PC12 cells contain
      acidic and neutral endonucleases, while nuclei from undifferentiated PC12 cells
      have only acidic endonuclease. The DNA ladder formation observed in isolated
      nuclei from neuronal differentiated PC12 cells at neutral pH requires both Ca(2+)
      and Mg(2+), and is sensitive to Zn(2+). The molecular mass of the neutral
      endonuclease present in neuronal differentiated PC12 cell nuclei is 32000 as
      determined by activity gel analysis (zymography). The properties of the neuronal
      endonuclease present in neuronal differentiated PC12 cell nuclei were similar to
      those of purified DNase gamma from rat thymocytes and splenocytes. Interestingly,
      in neuronal differentiated PC12 cells, internucleosomal DNA fragmentation is
      observed following NGF deprivation, whereas undifferentiated PC12 cells fail to
      exhibit DNA ladder formation during cell death by serum starvation. These results
      suggest that the DNase gamma-like endonuclease present in neuronal differentiated
      PC12 cell nuclei is involved in internucleosomal DNA fragmentation during
      apoptosis, induced by NGF deprivation.

PMID- 14646508
TI  - Effect of Fas+ and Fas- target cells on the ability of NK cells to repeatedly
      fragment DNA and trigger lysis via the Fas lytic pathway.
AB  - We and others have recently shown that human NK cells express the Fas ligand
      (FasL) constitutively and that they can trigger the lysis of Fas positive (Fas+)
      target cells (TC) by apoptosis. We have also previously demonstrated that NK
      cells exposed to sensitive TC temporarily lose their ability to lyse sensitive TC
      via the granule-mediated pathway and that this loss is recovered when inactivated
      NK cells (NKi) are incubated in medium supplemented with IL-2, IL-12 or IL-15. In
      this study, we investigated the fate of the Fas-lytic pathway in NK cells exposed
      to either Fas+ or Fas- TC. To this end, we exposed NK cells to Jurkat (Fas-) or
      Jurkat (Fas+) TC for up to 6 h, separated NK cells from the TC and assessed the
      residual lytic activity against K562, a traditional human NK cell target, Jurkat
      Fas+ and Jurkat Fas- TC. Fas lytic activity was determined in calcium free
      medium, in the presence or absence of two distinct Fas-blocking monoclonal
      antibodies and a Fas.Fc fusion protein. In parallel experiments, the extent of
      DNA fragmentation in the three TCs was also assayed by the JAM test. Our results
      indicate that: (i) NK cells exposed to susceptible Fas+ TC temporarily lose most
      of their lytic potential due to the granule-mediated pathway, while only
      partially losing the Fas-lytic pathway. They also partially lose their ability to
      fragment DNA. (ii) NK cells exposed to Fas+ TC completely recover the Fas lytic
      pathway and the ability to fragment DNA via the Fas/Fas ligand when incubated in
      medium supplemented with IL-2 for 18 h.

PMID- 14646509
TI  - Early features of apoptosis detected by four different flow cytometry assays.
AB  - The objective of this study was to investigate the sensitivity, specificity and
      reproducibility of some frequently used apoptosis assays. The degree of apoptosis
      was tested in two T-lymphoblastoid cell lines, HSB and Jurkat, in which apoptosis
      was induced by ionizing radiation. HSB and Jurkat samples were taken before, and
      0, 2, 4, 6, 8 and 24 h after irradiation with 6 and 10 Gray, or with 10 and 14
      Gray, respectively. Four frequently used flow cytometric techniques were
      evaluated: (i) Annexin V/Propidium Iodide assay, detecting the translocation of
      phosphatidylserine to the outer leaflet of the plasma membrane, simultaneously
      with preservation of the membrane integrity; (ii) Terminal deoxynucleotidyl
      Transferase (TdT) Uridine triphosphate (UTP) nick end labelling (TUNEL),
      revealing the presence of DNA strand breaks; (iii) DNA-flow cytometry, measuring
      DNA-stainability (DNA-fragmentation assay) and (iv) Phycoerythrin-labelled (PE)
      Apo2.7-assay, a monoclonal antibody against 7A6 antigen, a protein, which becomes
      exposed upon the mitochondrial membrane during apoptosis. As a general standard
      for identifying that apoptosis had occurred, the cells were assessed for the
      presence of DNA-laddering on agar gel electrophoresis and by demonstration of
      characteristic cell morphology. Results were as follows: Fluorescein
      Isothiocyanate (FITC)-labelled Annexin V/Propidium iodide flow cytometry appeared
      to be the most sensitive, the most specific and the most user-friendly test for
      measurement of apoptosis of cells in culture conditions in suspension. The
      expression of 7A6 antigen on the mitochondrial membrane appeared to be not
      specific for apoptotic cell death.

PMID- 14646510
TI  - UV-B irradiated cell lines execute programmed cell death in various forms.
AB  - We investigated changes typical for apoptosis in various cell lines after UV-B
      irradiation. Using established methods for detection of apoptosis we demonstrate
      changes of cellular morphology, phosphatidylserine (PS) exposure,
      ollgonucleosomal DNA fragmentation and generation of hypochrome nuclei. To
      isolated high-molecular-weight (hmwt) DNA fragments we engaged a new method
      avoiding pulse field gel electrophoresis. Most UV-B irradiated cell lines showed
      oligonucleosomal DNA fragmentation, hypochrome nuclei, morphological changes,
      annexin-V binding and positive TUNEL reaction. However, no oligonucleosomal DNA
      fragmentation could be detected in Raji and HaCaT cells. Whereas HaCaT cells
      displayed all other changes typical for apoptosis, Raji cells were TUNEL
      negative, formed low amounts of hmwt DNA and showed an 'atypically' low
      hypochrome shift. Nevertheless, UV-B irradiated Raji cells excluded propidium
      iodide (PI), bound annexin-V and stopped proliferation. This suggests that Raji
      cells underwent growth arrest with exposure of PS being the only feature of
      apoptosis. However, in the presence of phagocytes expressing the
      phosphatidylserine receptor these cells would share the removal pathway with
      apoptotic cells. Since UV-B induced programmed cell death differs in dependence
      of cells under investigation, the failure to detect oligonucleosomal DNA
      fragmentation or chromatin condensation is not suitable to exclude programmed
      (apoptotic?) cell death.

PMID- 14646511
TI  - Ultrastructural morphology of neuronal death following reversible focal ischemia
      in the rat.
AB  - Electron microscopy and terminal deoxynucleotidyl transferase (TdT) mediated dUTP
      biotin nick end-labelling (TUNEL) were used to illustrate the different stages
      and subcellular alterations of cell degeneration that occur in the striatum of
      the rat after transient focal ischemia. Degenerating neurons exhibited different
      morphological types: apoptosis Type 1 (aggregation of dense masses of chromatin
      beneath the 'intact' nuclear membrane) and Type 2 (high cytoplasmic
      vacuolization), and necrosis. These profiles were localized in different part of
      the striatum. Type 1 was found in the head of the caudate putamen, Type 2 in the
      middle part of the striatum and necrosis in the striatal core. These
      ultrastructural results demonstrated that apoptosis occurs in neurons following
      focal ischemia in the striatal penumbra. In contrast, necrosis can be observed in
      the ischemic core, the region maximally affected by the ischemia. Finally, the
      presence of astrocytes throughout both the penumbra and ischemic core displaying
      numerous cytoplasmic vacuoles suggested an activation of glial cells.

PMID- 14646512
TI  - Programmed cell death and the proteasome.
AB  - A characteristic feature of apoptotic cell death is the activation of a cascade
      of cytoplasmic proteases that results in the cleavage of a limited number of
      target proteins. A central role in these proteolytic events has been assigned to
      members of the capase family. However, the use of low molecular weight
      proteasomal inhibitors has also demonstrated that protein degradation or
      processing by the ubiquitin-proteasome system of the cell has a decisive impact
      on cell survival and death as well, depending on the cell type and/or the
      proliferative status of the cells studied. Treatment of proliferating cells with
      proteasome inhibitors leads to cell death, potentially involving an internal
      signalling conflict between accumulating levels of the cdk inhibitor p27Kip1 and
      c-myc. In contrast, in terminally differentiated cells the same compounds have
      the opposite effect of blocking apoptosis, possibly by preventing proteasome
      mediated degradation of a capase inhibitor. In this review the role of proteasome
      mediated proteolysis in the dying cell is discussed and apparently conflicting
      results are integrated into a working hypothesis which functionally locates the
      proteasome upstream of capase3-like enzymes.

PMID- 14646513
TI  - Cell surface exposure of phosphatidylserine during apoptosis is phylogenetically
      conserved.
AB  - Exposure of the aminophospholipid phosphatidylserine at the outer leaflet of the
      plasma membrane by apoptotic cells can trigger phagocytic removal of these dying
      cells. This functionality of phosphatidylserine exposure in the process of
      phagocytosis is indicated by in vitro studies of mammalian and insect phagocytes.
      We have studied the in vivo distribution of cell-surface exposed
      phosphatidylserine by injecting biotinylated Annexin V, a Ca2+ -dependent
      phosphatidyl-serine binding protein, into viable mouse and chick embryos and
      Drosophila pupae. The apparent binding of Annexin V to cells with a morphology
      which is characteristic of apoptosis and which was present in regions of
      developmental cell death indicates that phosphatidylserine exposure by apoptotic
      cells is a phylogenetically conserved mechanism.

PMID- 14646514
TI  - The anti-cancer drug etoposide can induce caspase-8 processing and apoptosis in
      the absence of CD95 receptor-ligand interaction.
AB  - Caspase-8 (FLICE) can associate with and be activated by CD95 (APO-1/Fas), an
      apoptosis-inducing member of the Tumour Necrosis Factor receptor family. We find
      that, in Jurkat T cells, the DNA damaging anti-cancer drug etoposide induces
      apoptosis and, surprisingly, processing of caspase-8. Therefore, we have
      investigated whether etoposide involves CD95 receptor activation. We find that
      etoposide does not induce CD95 ligand expression at the mRNA level. In addition,
      blocking of CD95 receptor function with a specific antibody does not inhibit
      etoposide-induced apoptosis. Apparently, in Jurkat cells, etoposide can induce
      caspase-8 processing and apoptosis in a CD95-independent fashion. Likewise, we
      find that thymocytes from the CD95-deficient lpr/lpr mouse strain readily undergo
      apoptosis in response to etoposide. Moreover, since inhibition of the secretory
      pathway with brefeldin A does not inhibit etoposide-induced apoptosis, we exclude
      the requirement for a newly synthesized receptor ligand to induce the apoptotic
      pathway. We conclude that, at least in certain cell types, etoposide does not
      require CD95 receptor function to induce caspase-8 processing and apoptosis.

PMID- 14646515
TI  - Caspase inhibition prevents staurosporine-induced apoptosis in CHO-K1 cells.
AB  - Apoptosis is a distinct form of programmed cell death that plays an important
      role in many biological processes. Although the phenotypes of apoptotic cells are
      well documented, little is known of the central mechanism leading to programmed
      cell death. Over the past few years, a number of ICE/CED-3 family proteases (also
      termed caspases) have been discovered and implicated as the common effectors of
      apoptosis. In this report, we demonstrate that induction of apoptosis in CHO-K1
      cells by staurosporine, a broad spectrum inhibitor of protein kinases, results in
      an increase in DEVD-dependent protease activity. These events were followed by
      nuclear DNA fragmentation and cell death. Inhibition of the DEVD-cleaving
      activity by a synthetic tetrapeptide inhibitor DEVD-CHO, blocked staurosporine
      induced downstream apoptotic phenotypes, such as morphological characteristics
      and DNA fragmentation. These results suggest that staurosporine-induced apoptosis
      in CHO-K1 cells is mediated through the CPP32/caspase-3-like cysteine proteases.

PMID- 14646516
TI  - Apoptotic differences in experimentally induced colorectal rat tumours.
AB  - The presence of apoptotic bodies and of intraepithelial lymphocytes (IELs) were
      assessed in colorectal adenomas and adenocarcinomas induced in 158 rats by two
      different carcinogens: 1,2 dimethylhydrazine (DMH) and glutamic acid pyrolysate
      (GLU-P-1 and 2). Apoptotic granules were present in 97.5% (n=40) of the 41 GLU
      induced adenomas and adenocarcinomas, but only in 20.5% (n=24) of the 117 DMH
      induced tumours. IELs were found in 95.1% (n=39) of the 41 GLU-induced tumours
      but only in 21.4% (n=25) of the 117 DMH-induced neoplasias. The differences were
      significant (p< 0.001). The presence of IELs and apoptotic granules in GLU
      tumours (and their absence in the majority of the DMH tumours) is new evidence
      that IELs are the cells from which many of the apoptotic granules--seen in
      colorectal neoplasias--derive. GLU neoplasias were induced following daily
      treatment, for 24 months (about half the life span of the animals) and DMH
      neoplasias by weekly doses, for a period of only 2.8-6 months. It would appear
      that 'slowly growing' colorectal GLU neoplasias often attract IELs and trigger
      lymphocytic apoptosis whereas 'quickly growing' DMH tumours seldom evoke those
      reactions.

PMID- 14646517
TI  - Calcium Dobesilate protects human peripheral blood mononuclear cells from
      oxidation and apoptosis.
AB  - The antioxidant effects of Calcium Dobesilate (CD, Doxium) were investigated in
      relation to the oxidative status, apoptosis and in vitro proliferation of human
      peripheral blood mononuclear cells (PBMC) isolated from healthy donors. CD alone
      did not modify cell growth in vitrountil 10 microM. This molecule counteracted
      oxidative damages generated by the high reducing sugar dR and was shown to reduce
      apoptosis by delaying both membrane permeability changes and DNA fragmentation.
      CD 10 microM affected in a time-dependent dynamics several parameters
      representative of the cellular oxidative status. In particular, CD significantly
      increased the activity of glutathione S-transferase (GST) after three days of
      treatment and also, but to a lower extent, the activity of gamma
      glutamyltransferase (gamma-GT). Both enzymes are known to be involved in the
      glutathione (GSH) metabolic cycle. This enzymatic behaviour was reversed at seven
      days of treatment, with a significant GST decrease and a gamma-GT activation.
      After seven days of CD exposure, the intracellular GSH content was enhanced and
      this resulted in a dramatic decrease in lipid peroxidation, underlining the
      powerful antioxidant properties of CD in human PBMC.

PMID- 14646518
TI  - Induction of apoptosis by a gonadotropin-releasing hormone agonist during early
      pregnancy in the rat.
AB  - We have demonstrated that continuous administration of a GnRH-agonist (GnRH-Ag)
      in the rat during early pregnancy suppressed plasma progesterone levels within 8
      h after the commencement of treatment. The purpose of the present study is to
      evaluate the hypothesis that in vivo GnRH-Ag treatment induces apoptotic cell
      death during early pregnancy. Rats were treated individually on day 8 of
      pregnancy with 5 microg/day of GnRH-Ag via an osmotic minipump. Sham-controlled
      rats received no treatment. Rats were killed at 4, 8 or 24 h after the treatment.
      At autopsy, blood samples were obtained and ovaries were removed. The corpora
      lutea (CL) from one ovary were removed for DNA laddering and RNA studies. As
      early as 8 h after the commencement of treatment, GnRH-Ag suppressed serum
      progesterone levels as expected, and increased the degree of DNA degradation in
      the CL that was time-dependent. At 24 h after the treatment, GnRH-Ag increased
      the Bax, a cell death gene, expression in the CL. Collectively, these data
      suggest that GnRH-Ag treatment induces apoptosis during early pregnancy in the
      rat.

PMID- 14646519
TI  - Intraepithelial lymphocytes vs. colorectal neoplastic cells: who is winning the
      apoptotic battle?
AB  - Intraepithelial lymphocytes (IELs) and Intraepithelial apoptotic granules (AGs)
      are found in the vast majority of colorectal adenomas, less frequently in
      incipient carcinomas and occasionally in advanced colorectal carcinomas. In
      colorectal adenomas, the activated and cytotoxic IELs undergo apoptosis by a Fas
      FasL mechanism. In advanced invasive carcinomas lacking IELs, that mechanism
      cannot be activated. On the other hand, the peritumoural lymphocytes which
      surround some advanced invasive carcinomas may abrogate to-be-metastatic tumor
      cells, as treated cancer patients with peritumoural lymphocytes have a better 5
      years' survival than those without that peritumoural barrier. In colorectal
      adenomas the host reaction (IELs) dysplastic cells Fas-dependent confrontation
      seems to prevent rapidly proliferating adenomas from becoming rapidly invasive
      carcinomas, since that process takes 10 to 20 years to evolve.

PMID- 14646520
TI  - Caspase-2/NEDD-2 protease mediates execution of apoptosis in AK-5 tumor cells.
AB  - AK-5 tumour cells have been shown to undergo apoptosis in vitro and in vivo. The
      efficient killing of tumour cells by necrosis and apoptosis leads to spontaneous
      regression of the tumour. To investigate a possible involvement of caspase-2/Nedd
      2 protease in AK-5 apoptosis, we introduced Nedd-2 gene in antisense orientation
      and showed inhibition of tumour cell apoptosis. Similarly introduction of the bcl
      2 gene in tumour cells also inhibited the apoptotic programme. NK cells which
      have previously been shown to be the effector cells also fail to induce apoptosis
      in Nedd-2 antisense and bcl-2 transfected clones whereas NK mediated cytotoxic
      activity is not altered in the transfectants. These results suggest participation
      of Nedd-2 protease in the induction of apoptosis in AK-5 cells leading to tumour
      regression.

PMID- 14646521
TI  - Role of XIAP protein, a human member of the inhibitor of apoptosis (IAP) protein
      family, in phytohemagglutinin-induced apoptosis of human T cell lines.
AB  - A new family of human genes xiap, hiap-1 and hiap-2, which are homologous to the
      baculovirus iap (inhibitor of apoptosis) genes cp-iap and op-iap, has been
      recently cloned and shown to suppress apoptosis after serum withdrawal or
      exposure to a free radical inducer. In order to examine the role of one of these
      human genes, namely xiap, in lymphoid cells, we studied XIAP expression, after
      PHA stimulation in three different human T cell lines. We report here that
      stimulation with PHA resulted in the human T cell lines undergoing apoptosis, as
      assessed by DNA fragmentation and by propidium iodide (PI) staining and flow
      cytometry. When XIAP protein expression was evaluated by Western blot, we
      observed that the induction of apoptosis by PHA was associated with a parallel
      decrease of XIAP expression. We also provide evidence that stably transfected
      Jurkat cells containing the xiap open reading frame became resistant to PHA
      induced apoptosis. These data suggest a role for XIAP protein in the regulation
      of apoptosis in lymphoid cells.

PMID- 14646522
TI  - Inhibition of protein synthesis sensitizes thermotolerant cells to heat shock
      induced apoptosis.
AB  - Hyperthermia is a potent inducer of apoptosis in many cell lines. A brief
      exposure to mildly elevated temperatures elicits a transient state of augmented
      resistance to subsequent thermal stress. Here we show that a hyperthermic
      treatment of 43 degrees C for 1 h is sufficient to induce apoptosis in the cell
      line HL-60. This observation is based on morphologic evaluation and on comet
      assay results (an extremely sensitive method of detecting and quantifying
      apoptotic DNA fragmentation in individual cells). The thermotolerance phenomenon
      was also verified in the same manner by giving the cells a brief 30 min sub
      lethal heat conditioning treatment at 43 degrees C followed by a 6 h incubation
      time prior to the administration of a lethal heat load (43 degrees C for 1 h). We
      observed a dramatic decrease in resultant apoptoses in the thermotolerized cells
      in comparison to unconditioned cells. We assessed the necessity of de novo
      protein synthesis in the protective phenomenon. When the conditioned cells were
      given a cycloheximide treatment prior to heat conditioning we saw a sensitization
      of the conditioned cells to secondary thermal injury.

PMID- 14646523
TI  - Butyrate-induced reversal of dexamethasone resistance in autonomous rat Nb2
      lymphoma cells.
AB  - The parental rat Nb2 lymphoma is a prolactin (PRL)-dependent T cell line.
      Exposure of a PRL-independent subline, Nb2-SFJCD1, to sodium butyrate (NaBT)
      causes transient reversal of their growth factor-independent proliferation in
      association with constitutive expression of protooncogenes pim-1 and c-myc. In
      the present study, we investigated the effect of NaBT treatment on the
      sensitivity of Nb2-SFJCD1 cells to dexamethasone (DEX)-induced apoptosis.
      Pretreatment with NaBT (2 mM, 72 h) partially reversed resistance to apoptosis in
      Nb2-SFJCD1 cells exposed to DEX (100 nM) for 12 h, assessed by flow cytometric
      analyses of DNA fragmentation. However, the cytolytic effect of DEX was abrogated
      by PRL in a time- and concentration-dependent manner. Evaluation of apoptosis
      associated gene expression in NaBT-pre-treated cultures incubated with DEX or
      DEX+PRL indicated that the apoptosis resistance did not stem from altered bcl-2
      or bax expression. However, there was a strong correlation between the resistance
      to DEX-activated apoptosis and their enhanced expression of pim-1 mRNA and
      protein. The results show that it is possible to reverse DEX-induced apoptosis of
      Nb2 pre-T cells and suggest the pim-1 gene product has an important role as a
      suppressor of this process, perhaps functioning as a mediator of PRL action.

PMID- 14646524
TI  - Apoptosis and Bcl-2 protein changes in L1210 leukaemic cells exposed to oxidative
      stress.
AB  - The aim of this study was to explore the dose- and time-dependent effects of
      hydrophilic peroxyl radical initiator 2,2'azobis(2amidinopropane)dihydrochloride
      (AAPH) on apoptosis, and on expression of Bcl-2 in L1210 leukaemic cells. We
      observed a progressive increase of intracellular concentration of oxygen free
      radicals (OFR), manifested by the rise of 6-carboxy-2', 7'
      dichlorodihydrofluorescein diacetate, di(acetoxymethyl ester) oxidation, during
      24 h of cells exposure to AAPH. Oxidative stress was associated with peroxidation
      of cellular lipids, which was demonstrated by the measurement of thiobarbituric
      acid-reactive substances and conjugated dienes. Analysis of cell viability by the
      use of trypan blue exclusion method revealed that AAPH reduced the ability of
      L1210 cells to multiply or survive. AAPH increased the number of leukaemic cells
      with typical features of apoptosis like condensation of chromatin, pyknosis and
      fragmentation of nucleus, followed by secondary necrosis. A characteristic
      internucleosomal DNA cleavage, visualized as a DNA 'ladder' consisting of
      fragments that are multiples of 180-200 bp was also observed. The intensity of
      apoptosis was dependent on AAPH concentration, time of cell exposure and the
      availability of growth factors and nutrients in extracellular environment (FCS
      concentration). The novel observation is the increase of Bcl-2 level in L1210
      leukaemic cells surviving an oxidative stress. The level of Bcl-2 protein
      significantly rose with increasing AAPH concentration, and time of cell exposure
      to this oxidant. This phenomenon could be the result of: (1) negative selection
      of cells with the lowest expression of bcl-2, being more susceptible to oxidative
      stress and (2) increased synthesis and/or decreased degradation of Bcl-2 protein
      as an adaptation to continuous OFR loading. In contrast to growth-promoting
      medium (10% FCS/RPMI), the maintenance medium (2% FCS/RPMI) did not cover cell
      requirements for progressive Bcl-2 increase at the highest AAPH concentration (2
      mM) applied in this study. Several observations indicate that the increased Bcl-2
      level in surviving L1210 leukaemic cells exposed to oxidative stress is a symptom
      of their natural defence against cellular lipids peroxidation and apoptosis.

PMID- 14646525
TI  - Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant
      phenotype of human tumor cell lines.
AB  - Since apoptosis is the primary mode of cell death induced by cisplatin, the role
      of apoptosis and apoptosis-related gene products in cisplatin resistance was
      investigated in four human cisplatin-resistant cell lines of different tumour
      type. A common feature of the resistant sublines was a reduced susceptibility to
      drug-induced apoptosis compared to parental sensitive lines. Loss of wild-type
      p53 function was not a general event associated with the development of drug
      resistance. An increased bcl-2 expression was found in resistant cells
      characterized by mutant p53 (A431/Pt and IGROV-1/Pt), whereas in osteosarcoma (U2
      OS/Pt) and in ovarian carcinoma (A2780/CP) cells with wild-type p53, bcl-2 levels
      were markedly reduced. U2-OS/Pt cells had a 16-fold increase in the level of Bcl
      xL protein. Stable transfection of U2-OS cells with bcl-xL cDNA conferred a low
      level of drug resistance to cisplatin, suggesting that overexpression of this
      gene contributes to the cisplatin-resistant phenotype of this osteosarcoma cell
      system. In conclusion, these observations suggest a variable contribution of
      apoptosis-related genes to cisplatin resistance depending on the biological
      background of the cell system and presumably reflecting different pathways of
      apoptosis.

PMID- 14646526
TI  - Life and death decisions: the role of the IAPs in modulating programmed cell
      death.
AB  - Multicellular organisms have evolved elaborate signal transduction pathways for
      maintaining homeostasis through the control of cell proliferation and death. The
      recent surge of interest in the regulation of programmed cell death has led to
      the rapid identification of many proteins involved in controlling and executing
      apoptosis. The inhibitors of apoptosis proteins (IAPs) constitute a family of
      highly conserved death suppressing proteins that were first identified in
      baculoviruses, and that has recently expanded to include at least two homologues
      in Drosophila melanogaster and four in rodents and humans. In this article we
      review the current state of IAP research. Two of the IAPs, HIAP-1 and HIAP-2,
      have been placed within the TNFalpha induced cell death pathway which involves
      two receptors for TNFalpha and multiple, overlapping signal transduction
      proteins. A third, X-linked gene termed XIAP, is ubiquitously expressed and
      appears to have a broad range of suppressor activity to a variety of apoptotic
      triggers. The fourth member, NAIP, has been identified as the protein product of
      a candidate gene for the inherited neuromuscular disorder, spinal muscular
      atrophy (SMA). The neuroprotective activity of NAIP in an in vivo model of
      cerebral ischemia has also been demonstrated.

PMID- 14646527
TI  - Expression of Bax, Bcl-2, Waf-1, and PCNA gene products in an immortalized human
      endothelial cell line undergoing p53-mediated apoptosis.
AB  - Transfection of the wild-type p53 gene into an immortalized human endothelial
      cell line (ECV-304) by recombinant adenoviral delivery resulted in high level
      expression of the wild-type p53 protein and induction of apoptosis. Increases in
      the number of apoptotic cells were observed within 12 h after infection of ECV
      304 cells with recombinant p53 adenovirus, as deter-mined by the appearance of
      internucleosomal DNA fragmentation ladders and by TUNEL and electron microscopic
      analyses. Control cells infected with a beta-galactosidase recombinant adenovirus
      exhibited little or no increase in apoptosis over uninfected cells. The
      expression of Waf-1 and Bax gene products were in-creased substantially in
      apoptotic ECV-304 cells as determined by Northern blot, reverse transcription-PCR
      and immunoblotting analyses. Lesser increases in the expression of the PCNA gene
      were detected in ECV-304 cells undergoing apoptosis. Both control and apoptotic
      ECV-304 cells did not express detectable levels of Bcl-2 mRNA or protein in
      Northern blotting and immunoblotting analyses, respectively. The data suggest a
      role for the Bax gene product in p53-mediated apoptosis of endothelial cells.

PMID- 14646528
TI  - Apoptosis induced in L1210 leukaemia cells by an inhibitor of the chymotrypsin
      like activity of the proteasome.
AB  - Of a number of factors involved in apoptosis, protease activity may play a
      crucial role. We show that N-benzyloxycarbonyl-Ile-Glu( O-t-butyl)-Ala-leucinal
      (PSI), a selective inhibitor of the chymotrypsin-like activity of the proteasome,
      induces massive apoptosis in murine leukaemia L1210 cells. At 50 nM
      concentration, PSI induces a block of cytokinesis, while higher concentrations
      (500 nM) cause S phase block and massive apoptosis. Z-Leu-leucinal, a specific
      calpain inhibitor, did not induce apoptosis. In contrast to previous reports, TNF
      alpha did not enhance apoptosis when combined with PSI. Our results suggest that
      proteasome inhibitors may be considered as potential anti-neoplastic agents.

PMID- 14646529
TI  - Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with
      low-dose paclitaxel-induced sub-G1 apoptosis.
AB  - Paclitaxel is a potential anti-cancer agent for several malignancies including
      ovary, breast, and head and neck cancers. This study investigated the kinetics of
      paclitaxel-induced cell cycle perturbation in two human nasopharyngeal carcinoma
      (NPC) cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with higher
      concentrations (0.1 or 1 micro M) of paclitaxel showed obvious G2/M arrest and
      then converted to a cell population with reduced DNA content, which was detected
      as a sub-G2 peak in the flow cytometric histographs. If a low concentration (5
      nM) of paclitaxel was used instead, transient G2/M arrest was observed in NPC
      cells, which subsequently converted to a sub-G1 form during the treatment period.
      Internucleosomal fragmentation and chromatin condensation were detectable in
      these sub-G1 and sub-G2 cells, suggesting that persistent or transient G2/M
      arrest is a prerequisite step for apoptosis elicited by varying doses of
      paclitaxel. The levels of cyclins A, B1, D1, E, CDK 1 (CDC 2), CDK 2 and
      proliferating cell nuclear antigen (PCNA) were unchanged in NPC cells following
      treatment with any concentration of paclitaxel; however, apoptosis-related cyclin
      B1-associated CDC 2 kinase was highly activated by paclitaxel even at
      concentrations as low as 5 nM, which is consistent with the finding that low-dose
      paclitaxel is also able to induce apoptosis in NPC cells. Activation of cyclin B1
      associated CDC 2 kinase seems to be an important G2/M event required for
      paclitaxel-induced apoptosis, and this activation of cyclin B1/CDC 2 kinase could
      be attributed to the increased activity of CDK 7 kinase.

PMID- 14646530
TI  - Non-expression of insulin-like growth factor-I receptor is associated with
      apoptosis: an ultrastructural study on rat ameloblasts.
AB  - Insulin-like growth factor-I (IGF-I) is a pleiotrophic polypeptide which appears
      to have roles both as a circulating endocrine hormone and as a locally
      synthesized paracrine or autocrine tissue factor. IGF-I plays a major role in
      regulating the growth of cells in vivo and in vitro and initiates metabolic and
      mitogenic processes in a wide variety of cell types by binding to specific type I
      receptors in the plasma membrane. In this study, we report the distribution of
      IGF-I receptors in odontogenic cells at the ultrastructural level using the high
      resolution protein A-gold technique. In the pre-secretory stage, very little gold
      label was visible over the ameloblasts and odontoblasts. During the secretory
      stage the label was mostly seen in association with the cell membranes and
      endoplasmic reticulum of the ameloblasts. Lysosome-like elements in the post
      secretory stage were labelled as well as multivesicular dense bodies. Very little
      labelling was encountered in the ameloblasts in the transitional stage, where
      apoptotic bodies were clearly visible. The maturation stage also exhibited
      labelling of the secretory-like granules in the distal surface. The presence of
      gold particles over the plasma membrane is an indication that IGF-I receptor is a
      membrane-bound receptor. Furthermore, the intracellular distribution of the label
      over the endoplasmic reticulum supports the local synthesis of the IGF-I
      receptor. The absence of labelling over the transitional ameloblasts suggests
      that the transitional stage may require the non-expression of IGF-I as a
      prerequiste or even a trigger for apoptosis.

PMID- 14646531
TI  - Oestradiol inhibits spontaneous and cisplatin-induced apoptosis in epithelial
      ovarian cancer cells: relationship to DNA repair capacity.
AB  - A prospective role of sex steroid hormones in the pathogenesis of common
      epithelial ovarian cancer remains equivocal. We hypothesized that oestradiol can
      protect ovarian cells from apoptosis by augmenting their DNA repair capacity. Two
      established oestrogen receptor-positive human cancer cell lines of ovarian
      surface epithelial origin (OVCAR-3, SKOV-3) were studied during short-term (24 h)
      subculture in the absence or presence of oestradiol-17beta and/or the DNA
      damaging chemotherapeutic agent cisplatin. Apoptosis was monitored among
      individual cells by in situ DNA fragmentation analysis. Basal rates of apoptosis
      were diminished by exposure to oestradiol (progesterone or testosterone were
      without effect). Oestradiol also suppressed apoptosis induced by cisplatin and
      enhanced the repair of a cisplatin-damaged reporter chloramphenicol-O
      acetyltransferase gene transfected into ovarian cells. The ability of oestrogen
      responsive ovarian cancer cells to efficiently repair DNA and thereby avoid
      apoptosis may be related to propensity for clonal expansion and drug resistance.

PMID- 14646532
TI  - Apoptosis induced by cadmium.
AB  - Cell death resulting from cadmium (Cd) intoxication has been confirmed to occur
      through apoptosis by morphological and biochemical studies. However it is still
      not clear whether Cd itself or metallothionein (MT) induced by Cd is the major
      factor responsible for the apoptosis. Although apoptosis is inducible by exposure
      of cells to various stimuli, the common pathway involved is generally accepted to
      be activation of endonucleases that induce internucleosomal cleavage of DNA,
      resulting in the 'ladder' formation observed upon agarose gel electrophoresis and
      the chromatin condensation seen by electron microscopy. Cd does not seem to
      activate the endonuclease in vitro. However, Cd itself can be associated with
      apoptosis through indirect oxidative stress by inhibition of antioxidant enzymes
      and possible interaction with zinc finger protein. In addition to the direct
      effect of Cd, MT appears to play dual roles in apoptosis induction: one as a Cd
      carrier by which Cd accumulates in the nucleus, and the other as an inhibitor of
      zinc finger proteins, which include transcriptional factors related to apoptosis
      such as the product of the apoptosis resistance gene A20. In this review, we
      demonstrated that the mode of cell death following Cd exposure is associated with
      intracellular movement of Cd and MT. A possible mechanism for Cd-induced
      apoptosis is also discussed.

PMID- 14646533
TI  - Regulation of apoptosis-associated proteins in cell death following transient
      focal ischemia in rat pups.
AB  - Apoptosis is a process whereby developmental or environmental stimuli activate a
      genetic programme to execute a specific series of events that culminate in the
      death and efficient disposal of a cell. Although a series of recent data
      suggested that neuronal death following cerebral ischemia occurs through an
      apoptotic pathway, additional work is needed to establish the existence of a
      causal relationship between gene expression and DNA breaks in neuronal death. We
      investigate the role of p53 and Bax proteins in the induction of apoptosis
      induced by a new transient focal ischemia model in the rat pup. Our results show
      that wild-type p53 exerts a significant and time-dependent effect in the
      initiation of apoptosis, and that apoptosis is induced via DNA-strand breakage.
      Subsequently, increased Bax expression was observed in the cytoplasm of dying
      cells located in the infarct, whereas an increased Bcl-2 and hsp72 staining was
      detectable in survival cells and reactive glia present at the periphery of the
      lesion.

PMID- 14646534
TI  - Apoptotic index, Fas and bcl-2 in initial and relapsed childhood acute
      lymphoblastic leukaemia.
AB  - Seventy-two samples with initial and 23 samples with relapsed childhood acute
      lymphoblastic leukaemia (ALL) were investigated for apoptotic index (AI) and for
      Fas expression. AI was determined by DNA-fragmentation using deoxynucleotidyl
      terminal transferase and Fas expression by immunocytochemistry. bcl-2 mRNA
      expression was measured in 50 initial and 20 relapsed ALL. The patients were
      discriminated in groups with low and high AI, Fas-protein expression and bcl
      2mRNA expression by the mean value. AI was higher in relapsed than in initial
      ALL. The mean survival was significantly higher in patients with low AI (p=
      0.034). This was also true for the relapse-free interval, however, this result
      was borderline significant (p= 0.064). AI was directly correlated with expression
      of Fas and inversely correlated with bcl-2 mRNA expression. These results suggest
      that Fas and - with limitations - bcl-2 may influence the apoptotic process in
      childhood ALL and that enhanced apoptotic activity predicts poor prognosis.

PMID- 14646535
TI  - Apoptotic myocardial degeneration in thrombotic thrombocytopenic purpura.
AB  - The objective of this study was to determine whether the known myocardial
      degeneration in TTP is due to apoptosis. In TTP the heart is often involved,
      including the cardiac conduction system. Despite many platelet occlusions of
      small coronary arteries, there is little myocardial necrosis. Why the
      intermittent clinical episodes begin or end is unknown. Six hearts of patients
      dying with TTP were examined with routine and immunohistochemical stains. In
      addition to ventricular and atrial myocardium we examined the cardiac conduction
      system and coronary chemoreceptor. Numerous small coronary arteries were occluded
      with platelet thrombi in all these sites, including especially the sinus node, AV
      node and His bundle. The myocardial degeneration we found was conspicuously
      devoid of inflammation and the myocytes were relatively intact. These
      characteristics combined with TUNEL-positivity in the degenerating cells are
      typical of apoptosis. The focal degeneration in TTP is primarily apoptotic.
      Because circulating serotonin is carried by platelets and is released during
      aggregation, and because serotonin can cause a powerful cardiogenic hypertensive
      chemoreflex, we suggest that such a response may dislodge early platelet
      aggregations. Lessons from TTP may have special relevance for better
      understanding of myocardial reperfusion problems associated with angioplasty,
      thrombolysis and ischemic preconditioning.

PMID- 14646536
TI  - BAG-1 inhibits p53-induced but not apoptin-induced apoptosis.
AB  - BAG-1 has been identified as a Bcl-2-binding protein that inhibits apoptosis,
      either alone or in co-operation with Bcl-2. Here we show that BAG-1 inhibits p53-
      induced apoptosis in the human tumour cell line Saos-2. In contrast, BAG-1 was
      unable to inhibit the p53-independent pathway induced by apoptin, an apoptosis
      inducing protein derived from chicken anaemia virus. Whereas BAG-1 seemed to co
      operate with Bcl-2 to repress p53-induced apoptosis, co-expression of these
      proteins had no inhibitory effect on apoptin-induced apoptosis. Moreover, Bcl-2,
      and to some extent also BAG-1, paradoxically enhanced the apoptotic activity of
      apoptin. These results demonstrate that p53 and apoptin induce apoptosis through
      independent pathways, which are differentially regulated by BAG-1 and Bcl-2.

PMID- 14646537
TI  - Apoptosis induced by sodium butyrate treatment increases immunogenicity of a rat
      colon tumor cell line.
AB  - We have recently demonstrated that a treatment combining the cell differentiating
      agent sodium butyrate (NaBut) and interleukin-2 (IL2) resulted in a remission of
      established peritoneal colorectal carcinomatosis in rats. NaBut or IL2 treatment
      alone, never cured these tumour-bearing rats. In the present investigation, we
      report that NaBut-treatments induce apoptosis in the colonic cancer cells both in
      vitro and in vivo. We postulated that the significant therapeutic effect of
      NaBut/IL2 treatment can be mainly attributed to a NaBut-induced apoptosis of the
      tumoural cells increasing their immunogenicity. Indeed, treatment which combined
      apoptotic bodies (apobodies) as cell vaccine, plus IL2 immunotherapy
      significantly increased tumour remission and survival rate of the vaccinated
      rats, whereas IL2 treatment alone did not. We observed that the cured rats
      presented long-term protection against subsequent challenge with the parental
      tumour cells. This latter result suggests that these treatments generate an
      immune protection. This was confirmed by the presence, in the sera of the cured
      rats, of anti-tumoural antibodies directed against both the apobodies and the
      tumour cells, but not against normal colonocytes. In addition, we show that
      injections of apobodies before administration of the parental tumour cells
      results in a partial protection. We provide the first evidence that apobodies,
      derived from cancer cells after NaBut-treatment, induce a specific immune
      response against parental tumours cells. These data suggest that the distinctive
      immunologic properties of apobodies could provide a valuable tool in colorectal
      cancer immunotherapy.

PMID- 14646538
TI  - A chronology of cell death.

PMID- 14646539
TI  - Anti-apoptotic actions of cycloheximide: blockade of programmed cell death or
      induction of programmed cell life?
AB  - Cycloheximide (CHX), long recognized for its ability to inhibit protein
      synthesis, has been widely employed in studies of cell death to the extent that
      prevention of cell death by CHX has been used as prima facie evidence for a
      subtype of apoptosis called 'programmed cell death'. However, very rarely have
      investigators determined the effects of CHX on protein synthesis in their
      particular cell death paradigms. Recent findings are revealing alternative
      mechanisms of action of CHX that involve, ironically, stimulation of
      cytoprotective signalling pathways. For example, in embryonic rat hippocampal
      cell cultures CHX protects neurons against oxidative insults by a mechanism
      involving induction of neuroprotective gene products including Bcl-2. CHX induces
      increases in immediate early gene mRNA levels, and can activate several different
      kinases and transcription factors that are also activated by various insults and
      in response to anti-apoptotic growth factors. Concentrations of CHX that cause
      only a modest and/or transient decrease in over-all protein synthesis may prevent
      cell death by inducing cytoprotective signalling pathways ('programmed cell
      life'), whereas higher concentrations of CHX may prevent cell death by blocking
      the expression of 'death genes'. Establishing which of these anti-apoptotic
      mechanisms of action of CHX is operative in each cell death paradigm is clearly
      essential for proper interpretation of experimental results.

PMID- 14646540
TI  - Radiation-induced apoptosis and its relationship to loss of clonogenic survival.
AB  - Ionizing radiation can be an effective inducer of apoptosis and studies of many
      aspects of the pathways and mechanisms involved in this apoptosis induction have
      been published. This review stresses two aspects: the relationship between
      apoptosis and loss of clonogenic ability in irradiated cells and the time course
      for the appearance of apoptosis after radiation exposure. Although it was
      initially assumed that apoptosis occurred relatively quickly (within hours) after
      irradiation, evidence is presented and discussed here showing that apoptosis can
      occur at long times after irradiation (out to 20 days) in some cell types. This
      late, or delayed, apoptosis occurs after the cells have divided once or several
      times. The impact of delayed apoptosis on loss of clonogenicity after irradiation
      remains unclear. It seems likely that in some cell types, e.g., fibroblasts, the
      occurrence of late apoptosis is minimal and may have little impact on long term
      cell survival of the population, but in at least one instance, with a cell line
      of hematopoietic origin, it appears that late apoptosis can account for all the
      loss of clonogenicity in irradiated cells. The role of p53 in radiation-induced
      apoptosis is also discussed, with data presented showing that both p53-dependent
      and independent pathways for radiation-induced apoptosis exist, depending on the
      cell type.

PMID- 14646541
TI  - lpr T cells have lower ability to maintain bcl-2 expression ex vivo.
AB  - Autoimmune-prone lpr mice develop lymphoproliferative disorders, whereas their
      lymphocytes show accelerated apoptosis in culture. To elucidate whether the bcl-2
      protein, a repressor of apoptosis, is critical to the discrepancy between in vivo
      and in vitro survival, we examined bcl-2 expression in T cells from +/+ and lpr
      mice during culture. The expression levels of bcl-2 in cultured T cells from lpr
      mice were significantly down-modulated compared to those from +/+ mice and
      freshly obtained T cells. Besides, the reduction of bcl-2 protein levels was
      inhibited in T cells cultured in the presence of T cell receptor (TCR)
      signalling. These results suggest that lpr T cells might be susceptible to
      apoptosis in vitro due to down-modulation of bcl-2 by withdrawal of TCR
      signalling.

PMID- 14646542
TI  - Caspase-3/CPP32-like activity is not sufficient to mediate apoptosis in an IL-2
      dependent T cell line.
AB  - CTLL cells undergo apoptosis when cultured in the absence of IL-2. The IL-1beta
      converting-enzyme (ICE)/ caspase family has been implicated as an integral
      component of some forms of apoptosis. Numerous members of the caspase family have
      been identified, and it appears as if caspase-3/CPP32 plays a critical role.
      Previously we demonstrated that ICE/caspase-1 expression increases in CTLL cells
      during apoptosis; however, inhibition of ICE activity did not abrogate apoptotic
      death. The purpose of this report is to determine if other members of the caspase
      family are involved in T cell apoptosis induced by growth factor starvation. We
      show that cytosolic CPP32-like activity, as measured by the cleavage of DEVD-pNA
      and poly(ADP-ribose) polymerase (PARP), increases during apoptosis following
      growth factor deprivation. Cytosolic CPP32-like activity is inhibited in cells
      treated with the broad spectrum ICE family inhibitor boc-aspartyl(OMe)
      fluoromethylketone (D-FMK) and by VAD-FMK and DEVD-FMK which have greater
      specificity for CPP32-like ICE homologs; however, only the broad spectrum ICE
      inhibitor D-FMK inhibited apoptosis. Our results suggest that apoptosis induced
      by growth factor deprivation involves the caspase family, but increased CPP32
      like activity is not sufficient to mediate apoptosis induced by IL-2 starvation.

PMID- 14646543
TI  - Intracellular alkalinization in dexamethasone-induced thymocyte apoptosis.
AB  - Glucocorticoid can induce apoptosis of thymocytes, but its mechanism is not clear
      yet. In this study, we reported that dexamethasone-induced apoptosis was
      associated with intracellular alkalinization. Dexamethasone induced a higher
      percentage of apoptosis in 138 mM than in 50 mM NaCl, total abrogation of
      apoptosis was noted in NaCl-depleted culture medium. Highest apoptotic rate was
      observed in medium with pH 7.2, whereas it was partially and completely inhibited
      at pH 6.5 and pH 6.0, respectively. Intracellular pH was higher in pre-apoptotic
      thymocytes than non-apoptotic ones. The Na+/H+ antiporter inhibitor of 5-(N,N'
      dimethyl)-amiloride inhibited the dexamethasone-induced increase in pHi and
      apoptosis of thymocytes. Glucocorticoid antagonist RU486 also blocked the
      dexamethasone-induced effect. Furthermore, the apoptosis and increase in
      intracellular pH induced by dexamethasone were inhibited by cycloheximide,
      actinomycin D. It seems that intracellular pH is increased during the development
      of thymocyte apoptosis and inhibiting its increment would retard the rate of
      progression to cell death.

PMID- 14646544
TI  - The treatment with differentiation- and apoptosis-inducing agent, vesnarinone, of
      a patient with oral squamous cell carcinoma.
AB  - A patient with histopathological recurrent oral cancer with well-differentiated
      squamous cell carcinoma, was treated with differentiation- and apoptosis-inducing
      agent, vesnarinone, per os at a dose of 180 mg/day for 56 days and then at a dose
      of 60 mg/day for 93 days. The vesnarinone administration caused complete
      remission of the tumour. It has been found by immunohistochemical staining and
      PCR-SSCP analysis that the recurrent tumour has wild type p53 gene and relative
      high level of LeY expression as well as DNA fragmentation in the cancer cells, as
      assessed by nick-end labelling. These findings suggest that the cure of oral
      squamous cell carcinoma observed in this case might be associated with induction
      of differentiation and apoptosis of cancer cells by vesnarinone.

PMID- 14646545
TI  - All-trans retinoic acid induces apoptosis in acute myeloblastic leukaemia cells.
AB  - The effect of all-trans retinoic acid (ATRA) on leukaemia cell differentiation,
      proliferation and induction of apoptosis was studied by using autonomously
      growing blast cells isolated from eight patients with acute myeloblastic
      leukaemia (AML) either at diagnosis (n=4) or at relapse (n=4). No morphological
      or functional differentiation induced by ATRA was observed in any of the cases
      studied. In cell cultures, inhibition of leukaemia cell growth by ATRA was
      obvious, especially in the case of clonogenic cells, and it was both time- and
      concentration-dependent. Induction of apoptosis was more difficult to achieve.
      The cells retained over 90% viability in suspension when the ATRA exposure at any
      of the concentrations studied was 48 h or less. When the time of exposure to ATRA
      was longer than 48 h, the viability of the cells decreased in a concentration
      dependent manner. Apoptosis was observed morphologically in each of the AML cases
      with 10(-5) to 10(-8) M ATRA, if the incubation time of cells in ATRA was 72 h.
      The percentage of apoptotic cells increased with increasing ATRA concentrations
      from 12+/- 9% of 10(-8) M ATRA to 78+/-12% of 10(-5) M ATRA. The DNA
      electrophoretic method was able to detect apoptosis in all the AML samples
      exposed to 10(-7) and 10(-6) ATRA for 48 h and occasionally in cases where lower
      concentrations and longer exposure time were used. In conclusion, the present
      study shows that it is possible to induce apoptotic leukaemia cell death in vitro
      with ATRA in AML, and this effect is dependent on both concentration and exposure
      time.

PMID- 14646546
TI  - Apoptotic and necrotic cell death are both induced by electroporation in HL60
      human promyeloid leukaemia cells.
AB  - Cell death was induced by electroporation in HL60 cells, a human promyeloid
      leukaemia strain, in order to determine by both morphological and biochemical
      criteria whether necrotic or apoptotic processes occurred. Cells sampled at
      several times after electroporation were analyzed for the assessment of the
      following end-points: (i) chromosomal DNA fragmentation; (ii) cell viability;
      (iii) mono- and oligonucleosomes in the cytoplasmic fraction; (iv) apoptotic
      index; and (v) morphology of treated cells. The results indicate that about 50%
      of the cells killed by electroporation die through necrosis, while the remaining
      50% of the cells undergo apoptosis. Chromosome damage was also studied by
      cytogenetic analysis at metaphase. The possibility of killing tumour cells by
      electroporation, as a variant of electrotherapy, constitutes, in our opinion, a
      promising procedure in cancer therapy, avoiding the undesirable side effects
      normally derived from treatment with cytotoxic drugs.

PMID- 14646547
TI  - Evidence for an interleukin-1beta converting enzyme (ICE)-like activity distinct
      from ICE and responsible for ICE and CPP32 cleavage during apoptosis.
AB  - IL-1beta converting enzyme (ICE) and ICE-related proteases (IRPs) have been
      suggested to play a central role in apoptosis. We report the use of peptidic ICE
      inhibitors to reassess the role of this enzyme in the apoptosis induced by Fas or
      TNFalpha receptor ligation in Jurkat cells, U937 cells or monocytes. Our results
      show that inhibition of IL-1beta processing can be dissociated from inhibition of
      apoptosis. Indeed, two out of three com-pounds active on ICE are not inhibitory
      for apoptosis. This shows that ICE is not required for progression in the
      apoptotic pathway, but that one or several IRPs are necessary. In addition,
      Western blot analysis of cell lysates shows that both ICE and CPP32 precursors
      disappear rapidly after apoptosis induction, while ICH-1L precursor remains
      intact. Concomitant appearance of cleavage products can be visualized for CPP32,
      but not for ICE, suggesting that the former is proteolytically activated. In
      addition, this precursor cleavage can be blocked by an ICE inhibitor active on
      apoptosis. Altogether, our data support the hypothesis that one or several IRPs
      are necessary for apoptosis and are responsible for ICE and CPP32 cleavage during
      this process.

PMID- 14646548
TI  - Human keratinocytes maintain reversible anti-apoptotic defenses in vivo and in
      vitro.
AB  - Human keratinocytes proliferate and differentiate in an epidermal environment
      where induction of apoptosis can be triggered by ultraviolet radiation (UVR),
      activated lymphocytes and cytokines. The purpose of this study was to determine
      whether keratinocytes were susceptible to apoptosis induced by ionophore, ultra
      violet radiation, cytokines or crosslinking of CD95 (Fas/APO-1). In normal human
      skin exposed to two minimal erythema doses of ultraviolet radiation, suprabasal
      cells were the first keratinocytes to demonstrate apoptotic nuclei, and by 48 h
      apoptotic cells were identified throughout the mid to upper epidermis. However,
      most keratinocytes resisted apoptosis and UVR-induced apoptosis was not observed
      in basal cells, or in the most differentiated epidermis. Human keratinocytes and
      keratinocyte cell lines cultured in vitro developed maximal apoptosis 48 h after
      radiation. Human keratinocytes cultured in full growth factor supplements were
      resistant to UVR-induced apoptosis compared to keratinocyte cell lines or to a
      lymphoid cell line (HL60) susceptible to apoptosis. Keratinocyte cell lines were
      completely resistant to apoptosis induced by interferon-gamma, interferon-alpha,
      IL-2, IL-6, TNF-alpha, IL-1Ra, and GM-CSF. A subset of the cells in cultures of
      keratinocytes and transformed keratinocyte cell lines died by apoptosis in
      response to anti-Fas, IL-1alpha and TNF-alpha plus IFN-gamma and ionophore.
      Second passage freshly isolated human keratinocytes were much more resistant to
      apoptosis induced by ionophore, anti-Fas and cytokines than were transformed
      keratinocyte cell lines. Calcium shift to induce differentiation in second
      passage keratinocyte cultures made keratinocytes even more resistant to UVR
      induced apoptosis. This parallels the lack of UVR-induced apoptosis observed in
      the most differentiated keratinocytes in irradiated human skin. Both
      keratinocytes and keratinocyte cell lines express rather low levels of the anti
      apoptotic proteins bcl-2 and bcl-x compared to other apoptosis-resistant cell
      types. The differences between keratinocytes and keratinocyte cell lines in
      susceptibility to apoptosis are not explained by difference in expression of bcl
      2 or bcl-x. Finally, withdrawal of growth factors from keratinocytes decreased
      cell survival following UVR and increased the induction of apoptosis. Inhibition
      of protein synthesis with cyclo-heximide also made keratinocytes more susceptible
      to UVR-induced apoptosis, indicating that anti-apoptotic defences in cultured
      keratinocytes are dependent on active protein synthesis. These experiments show
      that the strong keratinocyte defences against apoptosis are stratified within the
      epidermis, and can be altered by differentiation and growth factor withdrawal.

PMID- 14646549
TI  - The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible
      implications for Parkinson's disease.
AB  - It is currently believed that excessive oxidant stress induced by metabolism of
      dopamine (DA), plays a major role in the pathogenesis of the selective
      nigrostriatal neuronal loss in Parkinson's disease. We recently showed that the
      neurotransmitter DA, in physiological concentrations, is capable of initiating
      apoptosis in cultured, post-mitotic sympathetic neurons. Bcl-2 is a proto
      oncogene that blocks apoptosis. We now report that Bcl-2 is a powerful inhibitor
      of DA toxicity in PC-12 pheochromocytoma cells. We induced stable expression of
      Bcl-2 in PC-12 cells by transfection with recombinant pCMV5 expression vector,
      containing mouse bcl-2 (coding-sequence) cDNA. Cells expressing Bcl-2 manifested
      marked resistance to otherwise lethal (300 uM) in vitroconcentrations of DA. This
      protective effect was reflected in the trypan-blue test of cell survival, 3 H
      thymidine incorporation and inhibition of the characteristic apoptotic
      morphologic alterations in scanning electron microscopic studies. Bcl-2 and
      associated control systems of apoptosis may have an important physiological role
      in restraining the apop-tosis-triggering potential of DA in nigrostriatal
      neurons. This novel field of research may yield insights into the pathogenesis of
      Parkinson's disease and lead to development of novel therapeutic approaches.

PMID- 14646550
TI  - Accumulation of major stress protein 70kDa protects myeloid and lymphoid cells
      from death by apoptosis.
AB  - The major heat shock protein, hsp70, is known to contribute to the mechanisms of
      cell protection against a variety of stress and cytotoxic factors, providing an
      increase of cell survival. Whether hsp70 could be implicated in the rescue of
      cells from stress-induced death proceeding on apoptotic pathway is not well
      established. Here we report that susceptibility of myeloid and lymphoid cell
      lines to apoptosis induced by heat shock or ethanol coincides with hsp70 content
      and can be modulated by changes in expression of this protein. Cells of lymphoid
      and myeloid lines differing in basal and inducible level of the protein were
      tested. The cells containing higher amounts of hsp70 (U937, Jurkat, Molt4) were
      more resistant to the apoptosis-inducing stimuli then cells which accumu-late
      lower amounts of the protein (HL60) and especially those lacking the protein
      (NSO). Inhibition of hsp70 accumulation by quercetin made cells more susceptible
      to the same apoptotic inducer. Enhancement of hsp70 expression by previous
      heating or by liposomal delivery of the exogenic protein to the cells lacking
      hsp70 made them more resistant to apoptosis. The possible mechanisms of the hsp70
      protective effect in apoptosis are discussed.

PMID- 14646551
TI  - Superoxide, nitric oxide, peroxynitrite and cytokine combinations all cause
      functional impairment and morphological changes in rat islets of Langerhans and
      insulin secreting cell lines, but dictate cell death by different mechanisms.
AB  - We have shown that nitric oxide treatment for 30-90 min causes inhibition of
      insulin secretion, DNA damage and disturbs sub-cellular organization in rat and
      human islets of Langerhans and HIT-T15 cells. Here rat islets and beta-cell lines
      were treated with various free radical generating systems S-nitrosoglutathione
      (nitric oxide), xanthine oxidase plus hypoxanthine (reactive oxygen species), 3
      morpholinosydnonimine (nitric oxide, super-oxide, peroxynitrite, hydrogen
      peroxide) and peroxynitrite and their effects over 4 h to 3 days compared with
      those of the cytokine combination interleukin-1beta, tumour necrosis factor-alpha
      and interferon-gamma. End points examined were de novo protein synthesis,
      cellular reducing capacity, morphological changes and apoptosis by acridine
      orange cytochemistry, DNA gel electrophoresis and electron microscopy. Treatment
      (24-72 h) with nitric oxide, superoxide, peroxynitrite or combined cytokines
      differentially decreased redox function and inhibited protein synthesis in rat
      islets of Langerhans and in insulin-containing cell lines; cytokine effects were
      arginine and nitric oxide dependent. Peroxynitrite gave rare apoptosis in HIT-T15
      cells and superoxide gave none in any cell type, but caused the most beta cell
      specific damage in islets. S-nitroso-glutathione was the most effective agent at
      causing DNA laddering or chromatin margination characteristic of apoptotic cell
      death in insulin-containing cells. Cytokine-induced apoptosis was observed
      specifically in islet beta cells, combined cytokine effects on islet function and
      death most resembled those of the mixed radical donor SIN-1.

PMID- 14646552
TI  - Spontaneous death of isolated adult rat cardiocytes in culture in association
      with internucleosomal cleavage of genomic DNA.
AB  - Many isolated adult cardiocytes do not survive beyond the early days of culture,
      but why they die has not been defined. We examined the possibility of apoptosis
      as the mechanism of death in cultured atrial and ventricular rat cardiocytes.
      Calcium-tolerant cardiocytes isolated by enzymatic dissociation were cultured
      with a medium containing FBS. Nucleosomal DNA fragmentation was detected by
      electrophoresis of DNA extracted from the cardiocytes, by immunohistochemical in
      situ DNA nick-end labelling of single cells, and by enzyme immunoassay for in
      vitro quantification in cytoplasmic fraction. Electrophoresis on the 5th to 14th
      day of culture revealed the ladder appearance characteristic of internucleosomal
      DNA cleavage in apoptosis with a consistent single peak of increased cytoplasmic
      DNA fragments. After the 14th day, the cytoplasmic DNA fragments decreased, and
      the ladder appearance could no longer be detected by electrophoresis. Cardiocytes
      positive with nick-end labelling were seen by the 5th day, and then increased in
      number over the remaining days. These results indicate that many isolated
      cardiocytes die spontaneously by apoptosis within the first 2 weeks of culture,
      suggesting a possible signal dependence for survival of adult cardiocytes. In
      addition to chemical signal depletion in culture, other possible explanations for
      this apoptosis include the absence of an electric signal during culture, lack of
      contractile activity, and initial loss of intercellular connections.

PMID- 14646553
TI  - Anti-apoptotic effect of Bcl-2 overexpression in RIN cells infected with Semliki
      Forest virus.
AB  - RIN cells were infected with recombinant Semliki Forest virus (SFV) particles
      containing the LacZ gene. X-gal staining showed 100% infectivity of the cell
      cultures and high-level expression of bacterial beta-galactosidase in these
      cells. The cytopathogenic effects of the SFV infection were studied by measuring
      the viability of the RIN cells. Comparisons between control RIN cells and Bcl-2
      overexpressing RIN cells were done 72 h post-infection. Significant differences
      in viability levels were observed. The control RIN cells showed in the MTT assay
      a mean value of 0.156+/-0.017 compared to 0.347+/-0.057 for the RIN/Bcl-2 cells.
      FACS analysis of cells labelled with propidium iodide indicated that only an
      average of 4.5+/-0.5% of the control cells were viable 72 h post-infection, while
      44.5+/-3.5% of the RIN/Bcl-2 cells were still alive. Thus, the Bcl-2
      overexpression clearly protected the SFV-infected cells from undergoing
      apoptosis.

PMID- 14646554
TI  - Effects of BCL-2 overexpression on the sensitivity of MCF-7 breast cancer cells
      to ricin, diphtheria and Pseudomonas toxin and immunotoxins.
AB  - Immunotoxins are presently being evaluated as novel agents for cancer therapy.
      The direct mechanism by which immunotoxins kill cancer cells is inhibition of
      protein synthesis, but cytotoxicity due to induction of apoptosis has also been
      observed with these agents. Some cancers that express high levels of BCL-2 are
      relatively resistant to apoptosis inducing agents. It is therefore important to
      determine to what degree the toxicity of ricin, diphtheria toxin, Pseudomonas
      exotoxin and Pseudomonas exotoxin derived immunotoxins towards cancer cells can
      be attributed to inhibition of protein synthesis, and to what degree to
      subsequent induction of apoptosis. We compared the sensitivity of MCF-7 breast
      cancer cells that were stably transfected with a BCL-2 expression plasmid and
      thus protected against apoptosis and of MCF-7 cells transfected with a control
      plasmid towards ricin, diphtheria and Pseudomonas toxin, a Pseudomonas toxin
      derived immunotoxin (LMB-7) and tumour necrosis factor alpha (TNF). We found that
      BCL-2 mediated inhibition of apoptosis renders the cells almost completely
      resistant (1000-fold) to tumour necrosis factor, but the same cells were only 3
      10 fold more resistant to cytotoxicity induced by immunotoxin LMB-7 as well as
      Pseudomonas exotoxin, diphtheria toxin and ricin. We next studied several
      leukaemia cell lines with variable levels of BCL-2 expression and found them
      quite sensitive to a Pseudomonas exotoxin containing immunotoxin independent of
      the level of BCL-2. Our data indicate that although BCL-2 overexpression can have
      a modest effect on sensitivity to an immunotoxin, cell lines derived from
      patients are still very sensitive to immunotoxins.

PMID- 14646555
TI  - Serum withdrawal and etoposide induce apoptosis in human lung carcinoma cell line
      A549 via distinct pathways.
AB  - The molecular events associated with apoptosis induced by two distinct triggers
      (1) serum withdrawal and (2) etoposide treatment were investigated in the human
      lung carcinoma cell line A549. Although both serum withdrawal and etoposide
      treatment resulted in internucleosomal DNA fragmentation, the morphologic
      features were distinct. Serum deprived apoptotic cells appeared small, round and
      refractile, with little evidence of nuclear fragmentation; etoposide-induced
      apoptotic cells appeared enlarged and flattened and displayed prominent nuclear
      fragmentation. p53 and p21/waf1 protein levels were elevated in etoposide-treated
      cells, but not in cells subjected to serum with-drawal. Apoptosis induced by both
      treatments was accompanied by a significant reduction in Rb protein levels.
      However, etoposide treatment led to hypo-phosphorylation of Rb, while serum
      withdrawal did not alter the Rb phosphorylation pattern. Serum withdrawal-induced
      apoptosis was correlated with activation of JNK and suppression of ERK
      activities, while both JNK and ERK activities were slightly elevated during
      etoposid- induced apoptosis. Together, these results support the hypothesis that
      apoptosis induced by serum withdrawal and etoposide treatment occurs through
      different pathways and involves distinct mediators.

PMID- 14646556
TI  - Adriamycin (ADM) induced apoptosis in transitional cell cancer (TCC) cell lines
      accompanied by p21 WAF1/CIP1 induction.
AB  - Genotoxic stimuli, including anticancer drugs, induce apoptosis in cancer cells
      through increase of p53, p21WAF1/CIP1, at least in part. Bcl-2 and Bax modify
      this pathway or directly regulated by p53. Here we studied Adriamycin (ADM)
      induced apoptosis in four human bladder cancer cell lines in respect of p53,
      p21WAF1/CIP1 and Bcl-2 family proteins. After ADM, treatment bladder cancer cells
      underwent dose-dependent cell death with typical morphologic features of
      apoptosis. Among four cell lines RT4 with wt p53, low ratio of Bcl-2 to Bax and
      induction of p21WAF1/CIP1 after ADM treatment, was the most sensitive to
      induction of apoptosis. Thus, p53, p21WAF1/CIP1, Bcl-2 and Bax status might
      determine susceptibility of bladder cancer cells to ADM induced apoptosis.

PMID- 14646557
TI  - Apoptosis, cell proliferation and in vivo biological behaviour of primary and
      metastatic tumour cells of an AKR lymphoma variant.
AB  - The possibility that apoptosis and/or cell proliferation have a role in tumour
      progression in a murine T cell lymphoma was tested. The model consisted of the
      comparison of primary (PT) and metastatic tumour (MT) cells. The PT cells, but
      not the MT cells displayed a very pronounced tendency for spontaneous apoptosis.
      Proliferative capacity of MT cells was lower than that of PT cells, suggesting
      that it does not contribute to the metastatic phenotype in this system. Release
      from apoptosis does however, probably, play a role in the aggressiveness of the
      lymphoma.

PMID- 14646558
TI  - 5-Fluorouracil (5-FU) induced apoptosis in gastric cancer cell lines: role of the
      p53 gene.
AB  - We examined chemosensitivity to 5-fluorouracil (5-FU) in four human gastric
      cancer cell lines, by analyzing the expression of p53 and its related genes.
      Treatment with 1mM 5-FU induced variable degrees of apoptosis in the cultured
      cells. The apoptotic indices 72 h after treatment were approximately 14% in MKN
      74 (wild-type p53 gene), 12% in MKN-45 (wild-type), 3% in MKN-28 (mutated) and
      0.5% in KATO-III cells (deleted), respectively. On the other hand, 50 microM 5-FU
      had little effect on the induction of apoptosis in MKN-74 cells, the value being
      approximately 2% after 72 h. Induction of P53 expression was noted 3 h after
      initiating the treatment, followed by the induction of P21/Waf1 after 6 h in both
      MKN-74 and MKN-45 cells. The same expression mode was noted in MKN-74 treated
      with 50 microM 5-FU. Conversely, the level of P53 expression was constant in MKN
      28 cells and absent in KATO-III cells, in which P21/Waf1 had never been induced.
      The Bax/Bcl-2 expression ratio was gradually elevated for up to 72 h in MKN-74
      and MKN-45 cells treated with 1mM 5-FU; in contrast, it was unchanged in MKN-28
      and KATO-III cells, and MKN-74 treated with 50 microM 5-FU. These results might
      indicate that (1) 1mM 5-FU induces apoptosis in cultured gastric cancer cells
      carrying the wild-type p53 gene, but not those carrying the mutated type or a
      gene deletion, and (2) the elevated Bax/Bcl-2 expression ratio plays a more
      crucial role than the higher expression of P21/Waf1 in the induction of p53- gene
      dependent apoptosis.

PMID- 14646559
TI  - Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK
      432 in combination with radiotherapy: association of the therapeutic effect with
      differentiation and apoptosis in the cancer cells.
AB  - Twenty patients with oral squamous cell carcinoma having mainly stage II or III
      lesions without distant metastasis, were treated with tegafur and streptococcal
      agent, OK-432, in combination with radiotherapy. As a consequence, 16 cases among
      the treated 20 cases showed complete remission by this therapy alone. Especially,
      we have found that the squamous cell carcinoma arising in non-keratinizing oral
      epithelium rather than in keratinizing oral epithelium has better response to
      this therapy. Among the 16 cases with complete remission (CR) by the current
      therapy, 10 cases were histopathologically diagnosed as well-differentiated
      squamous cell carcinoma and six cases as moderately differentiated squamous cell
      carcinoma. When we examined immunohistochemically the expression of various
      antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the
      presence of DNA fragmentation by nick-end labelling in the biopsy materials taken
      at the first visit to our clinic from 20 patients treated with the current
      therapy, the CR group showed a significantly increased LeY expres-sion level ( p<
      0.05) and DNA fragmentation rate (p< 0.05) as compared with the partial response
      (PR, n= 3) + no change (NC, n= 1) group. On the other hand, the CR group with
      respect to PCNA expression level was significantly decreased as compared with the
      PR + NC group ( p< 0.05). From these findings, it can be considered that the
      therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with
      radiotherapy is very effective, which may be associated with differentiation or
      apoptosis in oral squamous carcinoma cells. In addition, we present the clinical
      findings and results of immunohistochemical staining for the biopsy materials
      obtained from four CR cases treated with the current therapeutic method.

PMID- 14646560
TI  - Induction of tumour differentiation and apoptosis and LeY antigen expression in
      treatment with differentiation-inducing agent, vesnarinone, of a patient with
      salivary adenoid cystic carcinoma.
AB  - A patient with locally-advanced submandibular adenoid cystic carcinoma with
      poorly differentiated solid type, was treated with differentiation-inducing
      agent, vesnarinone, per os at a dose of 60 mg/day daily for 8 weeks. The
      vesnarinone administration caused marked regression of the tumour. In addition to
      conversion into the well-differentiated tubular type from the poorly
      differentiated solid type, the induction of apoptosis and LeY antigen was
      observed in the treated tumour. These findings indicate that vesnarinone might be
      a useful therapeutic agent for treatment of salivary cancer. Since we found the
      new expression of LeY antigen in the well-differentiated tubular lesion in the
      salivary adenoid cystic carcinoma treated with vesnarinone, we examined the LeY
      antigen expression in relation to tumour differentiation in five cases of
      salivary adenoid cystic carcinoma. Consequently, tissue sections from all of the
      adenoid cystic carcinoma examined showed no positive LeY staining, except for
      some areas in the tumour lesion with the tubular pattern including the
      histologically normal-appearing tissue adjacent to the tumour tissue. These
      findings suggest that there is the intimate relationship between the LeY antigen
      expression and tumour differentiation in human salivary adenoid cystic carcinoma.

PMID- 14646561
TI  - Apoptosis and mammary gland involution: reviewing the process.
AB  - Apoptosis is a process of programmed cell death. Mammary gland involution is a
      tissue remodelling process. Mammary epithelial cell apoptosis is an integral
      component of tissue remodelling but it is only one element. Equally important are
      the factors which degrade basement membrane and extracellular matrix. Both
      operations are required for completion of mammary gland involution. The primary
      apoptotic process occurs first and is temporally distinct from the second stage
      of involution typified by lobular-alveolar collapse. Local factors related to
      milk accumulation trigger the first stage, but loss of systemic hormonal
      stimulation governs the second stage. Changes in the expression patterns of cell
      cycle control genes and bcl-2 family member genes are found in the first stage.
      Proteinase gene activation dominates the second stage. These findings support a
      two stage model of mammary gland involution. Both mammary epithelial cell
      apoptosis and mammary gland remodelling advance through a process which includes
      both loss of survival factors and gain of death factors. This review focuses on
      signalling pathways and genetic controls which are activated and repressed during
      mammary gland involution.

PMID- 14646562
TI  - Cell cycle specificity of apoptosis during treatment of leukaemias.
AB  - This review summarizes our observations on the mechanism of induction of
      apoptosis in vitro in leukaemic cell lines and in vivo in patients with leukaemia
      undergoing chemotherapy, in relation to the cell cycle. Multiparameter flow
      cytometric methods allowed us to identify apoptotic cells and position them with
      respect to their cell cycle phase. Several antitumor agents of different classes
      have been characterized in terms of the cell cycle phase specificity of induction
      of apoptosis. Three types of apoptosis could be distinguished in relation to the
      initial damage to the cell vis-a-vis cell cycle position: (1) homo-phase
      apoptosis where the cells underwent apoptosis during the same phase in which they
      were initially affected; (2) homo-cycle apoptosis, where the cells underwent
      apoptosis during the same cell cycle in which they were initially affected, i.e.,
      prior to or during the first mitosis, and (3) post-mitotic apoptosis, where cells
      underwent apoptosis during the cell cycle(s) subsequent to that in which the cell
      was initially affected, most likely at the G1 or G2 checkpoints of these
      cycle(s). Four ranges of drug concentration can be distinguished in vitro for
      most drugs, where either: (1) no immediate effects; (2) cytostasis or post
      mitotic apoptosis; (3) homo-cycle or homo-phase apoptosis; or (4) necrosis are
      observed. Analysis of cell death of blast cells from peripheral blood or bone
      marrow of over 250 leukaemia patients (AML, ALL, CML in blast crisis) treated
      with various drugs during routine chemotherapy reveals that in the case of DNA
      topoisomerase inhibitors (e.g., mitoxantrone, VP-16) apoptosis is often rapid
      (peaks at 1-2 days after drug administration) and has features of homo-phase
      apoptosis. In contrast, cell death observed after administration of paclitaxel
      (taxol) or cytarabine (cytosine arabinoside) occurs later and has features of
      post-mitotic apoptosis: the cells divide but die in G1 of the subsequent
      cycle(s).

PMID- 14646563
TI  - Differential gene expression in apoptotic 32Dcl3 cells: induction of
      metallothionein.
AB  - Growth factor deprivation induced cell death of the hematopoietic cell line
      32Dcl3 is widely used as a model system to study apoptotic signalling pathways.
      Here we show that the onset of cell death after IL-3 withdrawal can be strongly
      delayed by either cycloheximide or actinomycin D, indicating that de novo protein
      synthesis is required. Subtractive cDNA library hybridization was used to
      identify genes upregulated in apoptotic 32Dcl3 cells. Here we present data
      showing metallothionein-I (MT-I) mRNA transiently upregulated by a factor of
      three- to 20-fold. Increased levels of total MT-I+II protein after IL-3
      withdrawal were demonstrated. An induction of MT-I RNA as well as of MT-I+II
      total protein was also observed in serum deprived NIH3T3 fibroblasts. Testing the
      effect of different inducers of apoptosis on 32Dcl3 cells we found that only IL-3
      withdrawal and ethanol treatment led to an upregulation of MT-I mRNA level. Since
      MTs are believed to play a role in the metabolism of zinc, we tested the effect
      of zinc on induced cell death. When 32Dcl3 cells are treated with zinc (50-300
      microM) in the absence of IL-3, loss of viability as well as degradation of the
      cellular DNA were delayed, indicating that zinc represses apoptosis. On the other
      hand zinc pre-treatment induced MT expression and accelerated the onset of
      apoptosis. Our data, therefore, suggest that MT exerts a proapoptotic function.

PMID- 14646564
TI  - HIV-1 envelope glycoproteins-mediated apoptosis is regulated by CD4 dependent and
      independent mechanisms.
AB  - The progressive loss of CD4 T lymphocytes is one of the hallmarks of HIV
      infection. The reverse correlation observed in vivo, between plasmatic HIV levels
      and CD4 T lymphocyte counts, supports the concept that direct HIV-mediated cell
      death contributes to this depletion. Previously, we and others have demonstrated,
      in vitro, that interactions between membrane-expressed HIV-envelope glycoprotein
      complexes and CD4 ecto-molecules are critical to cell killing which occurs mainly
      by apoptosis. Here, by the use of a co-culture model, in which chronically HIV-1
      infected cells trigger apoptosis in uninfected CD4+ target cells, we have
      investigated the role of different CD4 domains in HIV envelope-mediated
      apoptosis. Target cells were A201 lymphoblastoid cell lines expressing wild-type
      CD4 or mutant forms of CD4. We show that the cytoplasmic domain of CD4 was not
      required for apoptosis induction. In contrast, the HIV permissive cell line
      expressing a CD4/CD8 chimeric molecule which contains only the first 171 amino
      acids of CD4, appeared to be resistant to HIV-induced apoptosis; thus suggesting
      that the D3-D4 CD4 module plays somewhat a regulatory role. Pre-treatment of wild
      type CD4 expressing target cells by the phorbol ester PMA which leads to down
      regulation of CD4, completely abolished apoptosis. Interestingly, in cells
      expressing CD4 devoid of its cytoplasmic domain, PMA blocked partially cell death
      without affecting, as expected, the CD4 expression. Taken together, these results
      demonstrate that although CD4 expression is essential for HIV envelope induced
      apoptosis, the apoptotic signal could be delivered in the absence of its
      cytoplasmic domain. Consistent with this, we suggest that other membrane
      associated molecule(s) are recruited for the signalling to initiate apoptosis.

PMID- 14646565
TI  - HIV-gp120 induced cell death in hematopoietic progenitor CD34+ cells.
AB  - Haematologic abnormalities accompany the majority of HIV-1 infections. At present
      it is unclear whether this is due directly to HIV infection of hematopoietic
      progenitor cells, or whether this results from an indirect mechanism secondary to
      HIV infection. Here we provide evidence for an indirect mechanism, whereby
      hematopoietic progenitor cells undergo HIV gp120-induced apoptosis (programmed
      cell death) even in the absence of HIV infection. Freshly isolated, purified
      human hematopoietic progenitor CD34+ cells, derived from both umbilical cord
      blood and bone marrow, co-expressed the CD4 marker at low density on their
      surface. Although these CD34+CD4+ cells theoretically should be capable of
      productive infection by HIV, we found that HIV-IIIB could not establish
      productive infection in these cells. Nonetheless, gp120 from IIIB could bind the
      cells. Thus, binding of gp120 did not correlate with infectivity. Furthermore,
      binding of gp120 was a specific event, leading to apoptosis upon crosslinking
      with anti-gp120 through a fas-dependent mechanism. If apoptosis is also observed
      in vivo even in uninfected hematopoietic cells, this could contribute
      significantly to the impairment in hematopoietic cell number and function. Our
      data suggest a novel indirect mechanism for depletion of CD34+ and CD34+-derived
      cells even in the absence of productive viral infection of these cells.

PMID- 14646566
TI  - A C-terminal domain of HIV-1 accessory protein Vpr is involved in penetration,
      mitochondrial dysfunction and apoptosis of human CD4+ lymphocytes.
AB  - We have previously shown that expression of HIV-1 vpr in yeast results in cell
      growth arrest and structural defects, and identified a C-terminal domain of Vpr
      as being responsible for these effects in yeast. In this report we show that
      recombinant Vpr and C-terminal peptides of Vpr containing the conserved sequence
      HFRIGCRHSRIG caused permeabilization of CD4+ T lymphocytes, a dramatic reduction
      of mitochondrial membrane potential and finally cell death. Vpr and Vpr peptides
      containing the conserved sequence rapidly penetrated cells, co-localized with the
      DNA, and caused increased granularity and formation of dense apoptotic bodies.
      The above results suggest that Vpr treated cells undergo apoptosis and this was
      confirmed by demonstration of DNA fragmentation by the highly sensitive TUNEL
      assay. Our results, together with the demonstration of extracellular Vpr in HIV
      infected individuals, suggest the possibility that extracellular Vpr could
      contribute to the apoptotic death and depletion of bystander cells in lymphoid
      tissues during HIV infection.

PMID- 14646567
TI  - Activation of a CPP32-like protease during L1210 cell apoptosis induced by thiol
      deprivation.
AB  - Reduced thiols (e.g., cysteine) are important in the maintenance of lymphocyte
      cell viability and growth. L1210 monocytic leukaemia cells were known to have a
      limited ability to uptake cystine, and they require cysteine for cell growth.
      L1210 cells underwent apoptosis when cultured without thiol-bearing and dithiol
      cleaving compounds, adding thiols suppressed the apoptosis and promoted cell
      growth. A specific inhibitor of interleukin-1 beta-converting enzyme (ICE)-like
      and CPP32-like proteases could suppress L1210 cell apoptosis induced by thiol
      deprivation. The cell lysates of apoptotic L1210 cells exhibited protease
      activity that could cleave DEVD-AMC, but not YVAD-AMC, and so CPP32-like
      proteases, but not ICE-like proteases, were activated and participated in
      apoptosis. The addition of thiols could suppress CPP32-like protease activation.
      Although the cell death-suppressor bcl-2-family proteins (bcl-2 and bcl-XL) were
      recently found to suppress the activation of CPP32-like proteases, the expression
      levels of death-suppressor bcl-2-family proteins did not change when thiols were
      added. These results suggest that reduced thiols maintain L1210 cell survival by
      inhibiting the activation of CPP32-like proteases without changing the anti
      apoptotic bcl-2-family protein expression.

PMID- 14646568
TI  - The restrictive proteolysis of alpha-fodrin to a 120 kDa fragment is not
      catalyzed by calpains during thymic apoptosis.
AB  - The alpha-subunit (240 kDa) of fodrin was found to be digested selectively to a
      120 kDa fragment during apoptosis of rat thymocytes in vivo and in vitro. This
      fragment was detected by an antibody (Ab) against full length alpha-fodrin, but
      not by the anti-N-terminal sequence (GMMPR) of the mu-calpain-generated 150 kDa
      fragment Ab or the anti-PEST sequence of alpha-fodrin Ab. On the other hand,
      basal levels of the 150 kDa fragment were constantly recognized by these three
      antibodies during apoptosis. The production of the 120 kDa fragment during
      apoptosis was not affected by the addition of calpain inhibitors such as Ac
      LLLnal and E-64d, despite inhibition of the generation of the 150 kDa fragment.
      When x-irradiated thymocytes were incubated in the presence of N-tosyl-L
      phenylalanyl chloromethyl ketone (TPCK), both production of the 120 kDa fragment
      and apoptosis were suppressed. Purified mu- and m-calpain did not catalyze the
      formation of the 120 kDa fragment from purified alpha-fodrin in vitro. These
      results suggest that a protease different from calpains is involved in the major
      process of alpha-fodrin proteolysis to a 120 kDa fragment during thymic
      apoptosis.

PMID- 14646569
TI  - Early effects in chemical-induced rat liver carcinogenesis: an
      immunohistochemical study following exposure to 0.04% AAF.
AB  - To investigate effects that distinguish AAF from incomplete carcinogens, the rate
      of cell death (apoptosis) and cell proliferation was studied at early stages of
      AAF induced rat liver carcinogenesis. Male Wistar rats were fed 0.04% AAF in the
      diet for 2, 6 and 16 weeks and immunohistochemical markers were measured in the
      liver. The formation of initiated cells and preneoplastic foci was followed by
      staining for GST-P (glutathione-S-transferase). GST-P-positive foci were present
      from 6 weeks on. Apoptosis was increased in the periportal area and in
      preneoplastic foci at all time points. Cell proliferation was enhanced in the
      periportal area in oval cells and in bile duct-like cells particularly at 2 and 6
      weeks and mainly in GST-P positive foci at 16 weeks. Notably, more cells always
      proliferated than were eliminated. Other apoptosis-related markers like p53 and
      FAS/Apo-1 could not be demonstrated in either normal hepatocytes, preneoplastic
      foci or in hepatocytes from treated animals. Scattered bcl-2 positive cells were
      present in livers at 16 weeks of treatment. The two cell growth and
      differentiation related proto-oncogenes c-FOS and c-JUN were increased in all
      treated animals at early stages. If feeding was stopped after 6 weeks, livers did
      not recover significantly within the following 10 weeks. The results support the
      complex effects of AAF in rat liver carcinogenesis. Chronic toxicity locally
      impairs the balance between cell proliferation and cell death and induces
      morphological alterations that promote the growth of initiated cells.

PMID- 14646570
TI  - Cytokeratin-19 associated with apoptosis and chemosensitivity in human cervical
      cancer cells.
AB  - Cytokeratins are one group of intermediate filament proteins responsible for the
      integrity of cell structure, and have been recently reported to play a role in
      conferring a drug resistance phenotype. MAb Cx-99 is a monoclonal antibody
      exhibiting the specificity toward its corresponding antigen which was recently
      identified as the cytokeratin-19 protein. In the present study, we found that the
      level of cytokeratin-19 in cervical cancer cells could be decreased by incubation
      of cancer cells with MAb Cx-99. The reduction of cytokeratin-19 level had a
      killing effect on cervical carcinoma SIHA and HeLa S3 cell lines. The DNA ladder
      pattern, convoluted nuclei and blebbing morphology were observed with these cells
      after exposure to MAb Cx-99 for 72 h, suggesting that the cytotoxic mechanism of
      reduced cytokeratin-19 was mediated by induction of apoptosis. Moreover, the MAb
      Cx-99 treatment could increase the cytotoxicities of cancer chemotherapeutic
      agents such as cisplatin and vinblastine to both cervical carcinoma cell lines.
      The LD80 values were at least 15-fold reduced when cancer cells were treated with
      cisplatin or vinblastine in the presence of MAb Cx-99. These results suggest that
      the functional role of cytokeratin-19 was associated with the apoptosis
      prevention and drug resistance of cervical cancer cells.

PMID- 14646571
TI  - [Application and efficacy of adefovir dipivoxil in hepatitis B virus-associated
      chronic liver diseases].
AB  - In therapy of chronic hepatitis B, there are new and exciting developments in
      antivirals such as nucleotide analogues. Adefovir dipivoxil is an oral prodrug of
      adefovir, a nucleotide analogue of adenosine monophosphate. This agent has a
      potent in vitro and in vivo effect against herpes virus, retroviruses, and
      hepadnaviruses. In the hepatitis B virus (HBV) setting, adefovir dipivoxil
      inhibits both the wild type and lamivudine-resistant HBV strains. The safety
      profile of adefovir dipivoxil 10 mg is excellent, but higher doses can produce
      renal tubular damage, particularly when the drug is used for prolonged therapy.
      Adefovir dipivoxil is an important new addition to the current first-line
      treatments for HBeAg positive and negative chronic hepatitis B, as well as being
      rescue therapy for lamivudine-resistant HBV strains. It is also licensed for use
      in adults with decompensated liver disease, as well as compensated liver disease
      where there is evidence of active viral replication, persistently elevated serum
      alanine aminotransferase levels and active liver inflammation and fibrosis.
      However, a longer follow-up is needed to establish the long term safety and
      efficacy of adefovir dipivoxil in patients with chronic HBV infection.

PMID- 14646572
TI  - [Clinical characteristics of colonic diverticulitis in Koreans].
AB  - BACKGROUND/AIMS: In western countries, symptomatic diverticulitis develops in
      about 20% of the population with colonic diverticula, and it is mainly located at
      the left-sided colon. The clinical characteristics of diverticulitis have rarely
      been investigated although its incidence is increasing in Asia including Korea.
      The aim of this study was to compare diverticulitis with asymptomatic
      diverticulosis and to compare the clinical characteristics of right-sided
      diverticulitis with those of left-sided diverticulitis. METHODS: We
      retrospectively investigated the medical records of the patients who had symptoms
      and signs of diverticulitis. Their diagnosis was confirmed with computed
      tomography, barium study, colonoscopy and/or operations at Samsung Medical Center
      from September 1998 to February 2002. The control cases of asymptomatic and
      incidental diverticulosis were randomly selected during routine health check-up
      after matching age and sex. RESULTS: Twenty-seven patients with diverticulitis
      (male : female = 14 : 13) were included. The mean age was 53 (27~86). The ratio
      of right and left diverticulitis was 20:7, which was similar to the ratio of
      diverticulosis. The complications, especially perforation, were more frequent in
      the patients with left-sided diverticulitis (p<0.05). CONCLUSIONS: Colonic
      diverticulitis is more prevalent at the right colon and left colonic
      diverticulitis has more complications than right colonic diverticulitis in Korea.

PMID- 14646573
TI  - [Is immunohistochemistry for MLH1 and MSH2 proteins a useful method for detection
      of microsatellite instability in sporadic colorectal cancer?].
AB  - BACKGROUND/AIMS: In order to identify microsatellite instability (MSI), the test
      based on the polymerase chain reaction (PCR) can be used. However, PCR is not
      routinely performed in all hospital laboratories. Recently, immunohistochemistry
      (IHC) for MLH1 and MSH2 proteins has been reported as a rapid and useful method
      for MSI. However, the efficacy of IHC in the detection of the MSI has not been
      well established. The aim of this study was to evaluate the usefulness of IHC in
      the detection of the MSI by comparing it with the test results using PCR in
      colorectal cancer (CRC). METHODS: Paraffin-embedded normal and tumor tissues from
      seventy-five patients who underwent surgical resection of CRC were used. Abnormal
      expression of MLH1 and MSH2 protein was determined by IHC using MLH1 and MSH2
      antibodies. Normal and tumor DNAs were obtained from thirty CRC tissues that
      showed abnormal expression of MLH1 and MSH2 proteins by IHC. The MSI status was
      confirmed by PCR using five markers. RESULTS: Thirty tumors showed abnormal
      expression of MLH1 and MSH2 proteins by IHC, but only three tumors out of them
      were confirmed to have MSI by PCR. CONCLUSIONS: This result suggests that IHC
      with MLH1 and MSH2 antibodies does not seem to be a useful method to identify MSI
      in CRC, therefore PCR is required for detection of the MSI.

PMID- 14646574
TI  - [Tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in Korean
      patients with inflammatory bowel disease].
AB  - BACKGROUND/AIMS: Although the importance of genetic susceptibility to
      inflammatory bowel disease (IBD) has been established by epidemiological studies,
      the genes involved remain poorly understood. The aim of this study was to assess
      the role of single nucleotide polymorphisms of tumor necrosis factor-alpha(TNF
      alpha) and interleukin-10 (IL-10) genes in genetic susceptibility of IBD.
      METHODS: Blood samples were obtained from 91 patients with ulcerative colitis
      (UC), 63 patients with Crohn's disease (CD), and 200 healthy controls (HC). DNA
      was extracted from blood leukocytes for IL-10 and TNF-alpha genotyping by single
      base extension reaction. Genotypes and allelic frequencies were compared between
      IBD patients and HC, and among subgroups of the patients. RESULTS: The frequency
      of -308A allele of TNF-alpha was significantly lower in CD patients than in HC
      (p=0.005). The frequency of -238A allele of TNF-alpha was significantly higher in
      CD patients with perianal lesion than those without perianal lesion. On the other
      hand, the frequency of -308A allele of TNF-alpha was significantly higher in ANCA
      positive IBD patients than ANCA-negative IBD patients. There were no significant
      differences in allelic frequencies in the promoter region of IL-10 between IBD
      patients and HC. CONCLUSIONS: The TNF-alpha gene polymorphisms at positions -308
      and -238 may have influences on the susceptibility to CD or the behavior of CD.

PMID- 14646575
TI  - [Usefulness of plasma tumor M2-pyruvate kinase in the diagnosis of
      gastrointestinal cancer].
AB  - BACKGROUND/AIMS: Pyruvate kinase (PK) is a key enzyme of glycolysis. Different
      isoforms of this enzyme are tissue-specifically expressed (M2-PK, M1-PK, R-PK, L
      PK). The concentration of the dimeric M2-PK is increased in a metabolic state of
      tumor cells. In this case, the dimeric M2-PK is termed Tumor M2-PK. We
      investigated EDTA-plasma of 73 patients with gastrointestinal (GI) cancer and 61
      healthy controls to evaluate its significance in diagnosing GI cancer. METHODS:
      Plasma Tumor M2-PK was measured using an ELISA assay based on two monoclonal
      antibodies which specifically react with the dimeric Tumor M2-PK. RESULTS: The
      sensitivity of Tumor M2-PK was 67.1% for all GI cancers, that of CA 19-9 was
      38.4% and that of CEA was 34.3%. The specificity of Tumor M2-PK was 91.8%
      (cutoff=20 U/mL). Tumor M2-PK showed a high sensitivity in gastric cancer
      (62.2%), colorectal cancer (66.7%) and bile duct cancer (75.0%). In colorectal
      cancer, the combination of Tumor M2-PK with CEA resulted in a remarkable increase
      in the sensitivity (86.2%). The average Tumor M2-PK levels were generally
      elevated in the metastatic GI cancer patients compared to nonmetastatic patients,
      especially in stomach cancer with statistical significance (p=0.005).
      CONCLUSIONS: Tumor M2-PK in EDTA-plasma seems to be a new valuable tumor marker
      in GI cancer.

PMID- 14646576
TI  - [Colonic transit time in patient with liver cirrhosis].
AB  - BACKGROUND/AIMS: The colonic transit time in patients with liver cirrhosis has
      not been studied extensively in South Korea. Thus, the authors investigated the
      differences of colonic transit time between cirrhotic patients and normal
      controls with attention to factors that affect this change. METHODS: Fifteen
      cirrhotic patients and 15 controls were included in this study. To exclude any
      organic diseases, colonoscopy was preceded. The colonic transit time was measured
      by taking plain abdominal films on the 4th and 7th days after ingestion of
      radiographic non-absorbable colon markers for 3 days. RESULTS: The colonic
      transit time was 10.7 +/- 2.6 hours and 24.0 +/- 4.1 hours for cirrhotic patients
      and controls, respectively, indicating that the transit time in cirrhotic
      patients is much faster (p<0.05). The transit time for each segment of the colon
      was also measured. For the ascending colon, average transit time of the cirrhotic
      patients and controls were 5.60 +/- 1.93 and 6.88 +/- 1.77 hours respectively.
      For the descending colon, those were 2.80 +/- 1.04 and 10.80 +/- 2.59 hours
      (p<0.05), while those in the rectosigmoid portion were 2.32 +/- 0.81 and 4.96 +/-
      1.19 hours, respectively. These results indicated that a significant difference
      is present in the descending colon. Additionally, the transit time is correlated
      with age and albumin level (B=0.760, p<0.05 and B=7.498, p<0.01, respectively).
      CONCLUSIONS: The colonic transit time of cirrhotic patients is faster than that
      of control, especially in the descending colon.

PMID- 14646577
TI  - [The role of hepatitis C virus core protein on liver fibrogenesis: a study using
      an in vitro co-culture system].
AB  - BACKGROUND/AIMS: The study of liver fibrogenesis by hepatitis C virus (HCV) has
      been limited due to the lack of an efficiency in vitro culture systems. In the
      present study, we investigated whether or not HCV core protein is directly
      related to liver fibrogenesis through stimulation of hepatic stellate cells
      (HSC). METHODS: Human and rat HSC were isolated and we established an in vitro co
      culture system of a stable HepG2-HCV core cell line which was transfected with
      HCV core gene and primary HSC. We performed immunocytochemical staining and
      Western and Northern blot analysis in the stimulated HSC by HCV core protein to
      identify the expression of transforming growth factor beta1 (TGF-beta1),
      transforming growth factor beta receptor II (TGFbeta R II), alpha-smooth muscle
      actin (alpha-SMA) and connective tissue growth factor (CTGF). The expression of
      matrix metalloproteinase-2 (MMP-2) and collagen type I (Col I) in the culture
      media were measured by zymogram and ELISA, respectively. RESULTS: The expression
      of TGF-beta1 and CTGF was significantly higher in the stable HepG2-HCV core cell
      line than in HepG2 cells. Furthermore, the makers related to fibrosis such as
      alpha-SMA, TGF-beta1, Col I, TGFRII and MMP-2 were highly expressed in the co
      culture of stable HepG2-HCV core with HSC. CONCLUSIONS: HCV core protein may play
      a direct role in the fibrogenesis of chronic liver disease with HCV infection.

PMID- 14646578
TI  - [Clinical significance of serum CA 125 in patients with chronic liver diseases].
AB  - BACKGROUND/AIMS: The clinical significance of serum CA 125 levels in patients
      with chronic liver disease has not been widely appreciated in relation to the
      severity of the disease. We examined serum CA 125 levels in patients with chronic
      liver disease according to the severity of liver disease and the presence of
      ascites. METHODS: Fasting serum CA 125 levels were measured by a commercial RIA
      kit in 92 patients with chronic liver disease: 22 with chronic hepatitis and 70
      with liver cirrhosis (Child class A, 19; B, 28; C, 23). Forty-one patients (45%)
      had ascites. RESULTS: The patients with Child class C liver cirrhosis had
      significantly higher mean serum CA 125 level than those with class A (p<0.05). In
      Child class B patients, the mean serum CA 125 level was significantly higher in
      patients with ascites than in those without (p<0.05). A multiple regression
      analysis showed that the presence of ascites, serum albumin, and prothrombin time
      were independent factors related to the increase of serum CA 125 levels.
      CONCLUSIONS: The presence of ascites is more closely related to the increase of
      CA125 levels in patients with liver cirrhosis than the severity of liver disease.

PMID- 14646579
TI  - [Clinical and epidemiological analysis of a 20-year experience of surgically
      treated gallstone patients].
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the epidemiological
      characteristics and changing patterns of gallstone disease over the last 20
      years. METHODS: Four thousands and twenty gallstone patients who had received
      surgery at Seoul National University Hospital (1981 to approximately 2000) were
      analyzed according to time of treatment; period I: 1981 to approximately 1985
      (831 cases), period II: 1986 to approximately 1990 (888 cases), period III: 1991
      to approximately 1995 (1,040 cases) and period IV: 1996 to approximately 2000
      (1,261 cases). Data from 13 institutes in Korea reporting 13,101 gallstone cases
      were also reviewed with literature to elucidate the nation-wide trends. RESULTS:
      The number of gallstone cases has gradually increased. A female-predominance was
      not observed (F/M=1.17-1.37). The CBD stone patients were older than the GB and
      the IHD stone patients. Over the study period, the relative portion of the GB
      stone group increased. The portion of CBD stone group decreased, while that of
      the IHD stone group was unchanged. The rural pattern of gallstone disease (low GB
      stone, high CBD and IHD stone) has become similar to the urban pattern. Such
      patterns are well agreed with the other literature reported in Korea.
      CONCLUSIONS: The pattern of gallstone disease in Korea has become similar to that
      in Western countries except a high prevalence of hepatolithiasis.

PMID- 14646580
TI  - [Usefulness and limitation of magnetic resonance cholangiopancreatography in
      patients with hepatolithiasis].
AB  - BACKGROUND/AIMS: Diagnosis of bile duct strictures as well as detection and
      localization of hepatolithiasis is important for an effective treatment of
      hepatolithiasis. For this purpose, endoscopic retrograde cholangiopancreatography
      (ERCP) and percutaneous transhepatic cholangiography (PTC) have been preferred as
      the diagnostic modalities of choice for hepatolithiasis. At present, magnetic
      resonance cholangiopancreatography (MRCP) is rapidly replacing ERCP. To determine
      the usefulness and limitation of MRCP for detecting hepatolithiasis and biliary
      strictures, we compared the result of MRCP with that of percutaneous transhepatic
      cholangioscopy (PTCS) as the standard reference. METHODS: Sixty-six patients with
      primary hepatolithiasis who underwent both MRCP and PTCS were enrolled. All
      patients underwent PTCS within 2 weeks of MRCP. The results of MRCP were reviewed
      by radiologists who were unaware of the clinical information about the location
      of hepatolithiasis and the presence of biliary strictures. RESULTS: The
      sensitivity and specificity of MRCP for detecting intrahepatic stones were 72.4
      and 90%, respectively. The sensitivity of MRCP for depicting intrahepatic bile
      duct strictures was 64%. The overall agreement between MRCP and PTCS for
      intrahepatic stones showed a good reliability (kappa value=0.64, p<0.05). The
      agreement of MRCP for hepatolithiasis with intrahepatic bile duct strictures with
      reference to PTCS showed a moderate reliability (kappa value=0.47, p<0.05).
      Imaging findings such as pneumobilia and hepatic parenchymal atrophy were related
      to false positive results in location of hepatolithiasis (p<0.05). CONCLUSIONS:
      MRCP has a good agreement rate in evaluation of intrahepatic stones and a
      moderate agreement rate in intrahepatic strictures, compared to PTCS.

PMID- 14646581
TI  - [A case of liver transplantation for primary sclerosing cholangitis].
AB  - Primary sclerosing cholangitis (PSC) is a rare disease entity. The medical
      therapy for PSC has not been reasonably beneficial. Thus liver transplantation is
      known to be the ultimate therapy. Because liver transplantation for PSC has been
      performed rarely in Korea, we report a case of liver transplantation for PSC with
      a review of the literature. A 35-year-old male was admitted to our hospital with
      recurrent jaundice for seven years. ERCP showed multiple strictures of
      intrahepatic duct and an irregularity of the extrahepatic duct wall. Despite
      medication and endoscopic treatment, liver functions did not improve and clinical
      status got worsened. Thus liver transplantation was performed for the correction
      of hepatic failure. Two months after transplantation, liver functions and general
      weakness gradually improved and now, one year after liver transplantation, the
      patient is in normal life.

PMID- 14646582
TI  - [A case of multiple bleeding pseudoaneurysms complicating acute pancreatitis].
AB  - Arterial pseudoaneurysm is rare but potentially a catastrophic complication of
      pancreatitis because it can cause massive gastrointestinal bleeding. Since
      surgical treatment of arterial pseudoaneurysm has a high mortality, percutaneous
      angiographic embolization of bleeding artery has recently been advocated as the
      alternative therapy. Acute hemorrhage into the peritoneal cavity or pseudocyst
      complicating chronic pancreatitis was frequently reported. However, multiple
      pseudoaneurysmal hemorrhage without pseudocyst complicating acute pancreatitis
      are extremely rare. Here, we present a case of multiple pseudoaneurysmal
      hemorrhage secondary to acute pancreatitis, which were managed successfully by
      percutaneous angiographic embolization.

PMID- 14646583
TI  - [A case of serous cystadenoma of the pancreas communicating with the pancreatic
      duct].
AB  - Serous cystadenoma of the pancreas is a rare disease and is usually benign.
      Mucinous cystadenoma, another cystic neoplasm of the pancreas, has a malignant
      potential. Serous cystadenoma is usually composed of many small cysts lined by
      small, cuboidal or flattened cells containing abundant glycogen. With the finding
      of endoscopic retrograde pancreatography, a communication between the cyst and
      pancreatic duct is observed occasionally in the mucinous cystadenoma, but rarely
      in the case of serous cystadenoma of the pancreas. We experienced a case of
      serous cystadenoma of the pancreas that had a communication between a cyst and
      the pancreatic duct.

PMID- 14646584
TI  - [A case of eosinophilic pancreatitis].
AB  - Eosinophilic pancreatitis is a rare disorder that may only be diagnosed after
      pancreatic resection under the suspection of a pancreatic tumor. We experienced a
      65-year-old female patient whose initial presentation suggested pancreatic
      cancer. Radiologic evaluation revealed a pancreatic mass-like lesion which was
      obstructing the main pancreatic duct. Endoscopic retrograde
      cholangiopancreatography (ERCP) showed double duct strictures involving the
      distal common bile duct and the main pancreatic duct. Serum IgE level was
      elevated. Percutaneous core needle biopsy with an 18-gauge needle was performed
      targeting the pancreatic lesion. The biopsy specimen revealed fibrotic
      interlobular septum and intralobular fibrosis with prominent eosinophilic
      infiltration. The patient was treated with oral prednisolone (40 mg/day). A
      plastic stent was inserted into the narrowed common bile duct. After three months
      of oral steroid therapy, symptoms and signs improved rapidly and serum IgE level
      was decreased. Abdominal computed tomography and ERCP revealed remission of
      pancreatic mass-like lesion.

PMID- 14646585
TI  - Phagocytosis induces superoxide formation and apoptosis in macrophages.
AB  - Phagocytosis by inflammatory cells is an essential step and a part of innate
      immunity for protection against foreign pathogens, microorganism or dead cells.
      Phagocytosis, endocytotic events sequel to binding particle ligands to the
      specific receptors on phagocyte cell surface such as Fcgamma recptor (FcgammaR),
      complement receptor (CR), beta-glucan receptor, and phosphatidylserine (PS)
      receptor, require actin assembly, pseudopod extension and phagosome closure. Rho
      GTPases (RhoA, Cdc42, and Rac1) are critically involved in these processes.
      Abrupt superoxide formation, called as oxidative burst, occurs through NADPH
      oxidase complex in leukocytes following phagocytosis. NADPH oxidase complex is
      composed of membrane proteins, p22PHOX and gp91PHOX, and cytosolic proteins,
      p40PHOX, p47PHOX and p67PHOX. The cytosolic subunits and Rac-GTP are translocated
      to the membrane, forming complete NADPH oxidase complex with membrane part
      subunits. Binding of imunoglobulin G (IgG)- and complement-opsonized particles to
      FcgammaR and CR of leukocytes induces apoptosis of the cells, which may be due to
      oxidative burst and accompanying cytochrome c release and casapase-3 activation.

PMID- 14646586
TI  - Gene expression profiling of oxidative stress on atrial fibrillation in humans.
AB  - Atrial Fibrillation (AF) is thought be caused by oxidative stress. Oxidative
      stress at the cellular level results from many factors, including exposure to
      alcohol, medications, cold, toxins or radiation. In this study we investigated
      gene transcriptional profiles on the human myocardial tissues from AF and
      oxidative stress conditions. Right atrial appendages were obtained from AF
      patients (n = 26) undergoing the Maze procedure, and from control patients (n =
      26) who were in normal sinus rhythm and undergoing coronary artery bypass graft
      operation. To examine the effects of oxidative stress on AF, we used radioactive
      complementary DNA (cDNA) microarrays to evaluate changes in the expression of
      1,152 known genes. This technology, which monitors thousands of genes
      simultaneously, gives us a better picture of the interactions between AF and
      oxidative stress. Total RNAs prepared from the retrieved tissues were used to
      synthesize 33P-labeled cDNAs by reverse transcription and hybridized to cDNA
      microarrays. Gene expression profiles showed that 30 genes were upregulated and
      25 were downregulated in AF patients compared with control patients. Moreover,
      comparison rank analysis revealed that the expression of five genes related to
      reactive oxygen species (ROS)-including flavin containing monooxygenase 1,
      monoamine oxidase B, ubiquitin specific protease 8, tyrosinase-related protein 1,
      and tyrosine 3-monooxygenase-increased by more than 2.0 of the Z-ratio, and two
      genes related to antioxidants including glutathione peroxidase 1, and heme
      oxygenase 2-decreased to the Z-ratio levels of < or = -2.0. Apparently, a
      balanced regulation of pro- and anti-oxidation can be shifted toward pro
      oxidation and can result in serious damage similar to that of human AF. Western
      blotting analysis confirmed the upregulation of tyrosinase-related protein 1 and
      tyrosine 3-monooxygenase and the downregulation of heme oxygenase 2. These
      results suggested that the gene expression pattern of myocardial tissues in AF
      patients can be associated with oxidative stress, resulting in a significant
      increase in ROS. Thus, the cDNA microarray technique was useful for investigating
      transcription profiles in AF. It showed that the intracellular mechanism of
      oxidative stress plays a pivotal role in the pathologic progression of AF and
      offers novel insight into potential treatment with antioxidants.

PMID- 14646587
TI  - Hypoxia activates signal transducers and activators of transcription 5 (STAT5)
      and increases its binding activity to the GAS element in mammary epithelial
      cells.
AB  - STATs (signal transducers and activators of transcription) are proteins with dual
      functions: signal transducers in the cytoplasm and transcriptional activators in
      the nucleus. STAT proteins act as transcription factors activated by
      phosphorylation on its tyrosine residues upon stimulation by various cytokines.
      The phosphorylated STAT molecules then form homo- or heterodimers through SH2
      mediated interaction and translocate into the nucleus to activate the
      transcription of various target genes. STAT5 recognizes the interferon-gamma
      activated site TTCNNNGAA (GAS sequence) in the promoter region of the beta-casein
      gene. Except for prolactin-dependent beta-casein production in mammary gland
      cells, the biological consequences of STAT5a activation in various systems are
      not clear. Here we showed that STAT5a was phosphorylated 10 min after
      desferrioxamine (DFO) treatment, and reached a maximum induction at 4 h in
      mammary epithelial cells (HC11) and transfected COS-7 cells. Under hypoxic
      conditions (2% O2), a maximal phosphorylation of STAT5a was observed within 6 h.
      EMSA (electrophoretic mobility shift assay) showed that DFO or hypoxia enhanced
      the binding activities of STAT5a DNA to beta-casein gene promoter in mammary
      epithelial cells (HC11) and transfected COS-7 cells. These results showed that
      DFO or hypoxia induces tyrosine phosphorylation of STAT5a and also increases the
      binding activity of STAT5a DNA in mammary epithelial cells. Our data suggest that
      the STAT5 may act as a mediator in hypoxia-mediated gene expression.

PMID- 14646588
TI  - Soluble glucocorticoid-induced TNF receptor (sGITR) induces inflammation in mice.
AB  - Glucocorticoid-induced TNF receptor (GITR) was a new member of the TNF/nerve
      growth factor receptor (TNFR/ NGFR) family and induced in murine T cells by
      dexamathasone. Recombinant soluble GITR (sGITR) induced an inflammation in
      peritoneal membrane and changes in spleen after i.p. injection of 3 mg/kg in
      C57BL/6 mice. Spleen was enlarged and percentage of neutrophils and monocytes
      were increased. The area of red pulp in spleen was increased, while that of white
      pulp was decreased after GITR injection. The thickening of membrane and
      neutrophil infiltration was observed in peritoneal membrane with increased
      myeloperoxidase activity. At later time, neutrophil infiltration moved to inside
      the tissue with tissue damage. GITR ligand and GITR were expressed constitutively
      on the surface of spleen cells and cells from peritoneal fluid. In contrast, no
      significant change in the spleen and in peritoneal membrane was observed in mice
      treated with LPS. GITR may play a role in body's inflammatory processes.

PMID- 14646589
TI  - Chronic activation of CREB and p90RSK in human epileptic hippocampus.
AB  - Mesial temporal lobe epilepsy (MTLE) is associated with severe neuronal death and
      reactive gliosis in hippocampus. However, the molecular mechanisms underlying
      these pathological changes remain unanswered. ERK has been reported chronically
      activated in reactive glia of human epileptic hippocampus. In the present study,
      we investigated which of the downstream signaling molecules of ERK would be
      involved in MTLE. Western blot analysis demonstrated that CREB and p90RSK were
      strongly activated in MTLE patients. Increase in the active forms of CREB and
      p90RSK resulted not only from the increase in their phosphorylation levels but
      also from the increase in the protein levels. Activation of CREB and p90RSK was
      noted in the whole subfields of hippocampus with Ammon's horn sclerosis (AHS)
      representing a distinctive cellular distribution. However, the common major
      change was present in proliferating reactive astrocytes. In contrast, their
      activation was not significant in adjacent temporal lobes despite the presence of
      a number of astrocytes expressing high levels of GFAP. Our results demonstrate
      that chronic activation CREB and p90RSK in the epileptic hippocampus may be
      closely associated with the histopathological changes of AHS.

PMID- 14646590
TI  - Grape extracts suppress the formation of preneoplastic foci and activity of fatty
      acid synthase in rat liver.
AB  - This study was conducted to examine the effects of dietary grape extracts on
      preneoplastic foci formation in rat hepatocarcinogenesis, and related hepatic
      enzymes. Male Sprague-Dawley rats were fed basal diet or grape diet containing
      15% concentrated grape extracts (68 bricks). The grape diet groups were divided
      into whole-period grape diet group (DEN-GW; grape diet group fed throughout
      experimental period) and postinitiation grape diet group (DEN-GP; grape diet
      group fed from post initiation stage) according to the starting time point of the
      grape diet. Hepatocarcinogenesis was induced by diethylnitrosamine (DEN; 200
      mg/kg bw) and 2/3 partial hepatectomy (DEN-B; DEN-treated basal diet group, DEN
      GW, and DEN-GP groups), while the control group treated with saline and sham
      operation (Control group). The formation of placental glutathione (GSH) S
      transferase positive (GST-P+) foci in DEN-GW group was moderately but
      significantly suppressed, however, not in DEN- GP group. Thiobarbituric acid
      reactive substances content of DEN-GW group was significantly lower than that of
      DEN-B group. The activity of fatty acid synthase (FAS) in the grape diet groups
      was decreased about 1/2 of the DEN-B group. The content of GSH and GSH peroxidase
      activity were increased by carcinogen treatment, but not modulated by grape diet.
      The activities of GSH S-transferase, p-nitrophenol hydroxylase, and catalase were
      not affected by diet or treatment. Conclusively, the grape diet-induced reduction
      of FAS activity that was expressed highly in neoplastic tissues, might be one of
      the contributing mechanisms of hepatic cancer prevention.

PMID- 14646591
TI  - Dexamethasone-induced differentiation of pancreatic AR42J cell involves
      p21(waf1/cip1) and MAP kinase pathway.
AB  - Dexamethasone converts pluripotent pancreatic AR42J cells into exocrine cells
      expressing digestive enzymes. In order to address molecular mechanism of this
      differentiation, we have investigated the role of mitogen-activated protein (MAP)
      kinase pathway and gene expressions of p21(waf1/cip1) and nuclear oncogenes (c
      fos and c-myc) during AR42J cell differentiation. Dexamethasone markedly
      increased the intracellular and secreted amylase contents as well as its mRNA
      level. However, cell growth and DNA content were significantly decreased. With
      these phenotypic changes, AR42J cells induced transient mRNA expression of
      p21(waf1/cip1) gene, which reached maximal level by 6 h and then declined
      gradually toward basal state. In contrast to p21(waf1/cip1), c-fos gene
      expression was transiently inhibited by 6 h and then recovered to basal level by
      24 h. Increased c-myc expression detected after 3 h, peaked by 12 h, and remained
      elevated during the rest of observation. Dexamethasone inhibited epidermal growth
      factor-induced phosphorylation of extracellular signal regulated kinase.
      Inhibition of MAP kinase pathway by PD98059 resulted in further elevation of the
      dexamethasone-induced amylase mRNA and p21(waf1/cip1) gene expression. These
      results suggest that p21(waf1/cip1) and nuclear oncogenes are involved in
      dexamethasone-induced differentiation and inhibition of MAP kinase pathway
      accelerates the conversion of undifferentiated AR42J cells into amylase-secreting
      exocrine cells.

PMID- 14646592
TI  - B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis.
AB  - Host immune response has been considered as an important disease-modifying factor
      of periodontitis, however, which immune cell(s) or factor(s) are involved in the
      destruction of periodontium remains unclear. Previously, we reported that
      osteoclastogenesis is enhanced by activated B cells but suppressed by activated
      CD8+ T cells. We present new data that B cells activated in the presence of Th1
      cytokines inhibit osteoclastogenesis. Purified murine B cells were activated with
      anti-IgD mAb, IL-4, and anti-CD40 mAb, in the absence (BTh2) or presence of Th1
      cytokines, either IL-2 (BIL-2) or IFN-gamma (BIFN-gamma). Each activated B cell
      population was co-cultured with RAW264.7 cells in the presence of soluble
      receptor activator of NF-kappaB ligand (sRANKL), and the effect on osteoclastic
      differentiation was evaluated. While BTh2 increased osteoclastogenesis, BIL-2 and
      BIFN-gamma suppressed it profoundly. To verify the mediating molecule(s), we
      analyzed cytokine profiles of the activated B cells. Compared to BTh2, BIL-2
      expressed increased amount of IFN-gamma and BIFN-gamma expressed decreased
      amounts of IL-4, IL-5, and IL-10. IFN-gamma was a key negative regulator of
      osteoclastic differentiation, and mediated the inhibition by BIL-2. These results
      suggest that Th1 cytokines may have new important roles in resistance to
      periodontitis, acting directly on osteoclasts or indirectly through B cells.

PMID- 14646593
TI  - Genomic organization and expression of parkin in Drosophila melanogaster.
AB  - We report here the isolation, characterization on genomic structure and
      expression of the D. melanogaster homolog of human parkin. The 2,122 bp parkin
      gene sequence contains six exons that form a 1,449 bp transcript encoding a
      protein of 482 amino acids. 151 bp of 5' and 112 bp of 3' untranslated regions
      were identified by a combination of 5'-RACE/primer extension and 3'-RACE,
      respectively. The 5' UTR contains three transcription initiation sites. Neither a
      classical TATA nor a CAAT box was found in the putative promoter sequence.
      However, binding sites for AhR-Arnt, AP4, NF1 and GATA transcription factors were
      identified. Transient transfection analysis of the 5' UTR confirmed its promoter
      activity in HEK 293 cells and SH-SY5Y neuronal cells using a dual luciferase
      reporting system. The amino acid sequence of D. melanogaster Parkin exhibits 42%,
      43% and 43% identity to that of human, mouse and rat, respectively, representing
      a 54 kDa protein band via western blot analysis. It shows a high degree of
      conservation in the Ubiquitin-like domain at the N-terminus (34%), the In-Between
      RING finger domains (IBR, 65-69%), and the RING finger domains at the C-terminus
      (56-57%). The expression pattern of D. melanogaster parkin varies during the
      developmental stages, with the highest expression in the adult stage as measured
      by competitive RT-PCR. From immunostainings of the embryo, D. melanogaster parkin
      was expressed slightly higher in the central nervous system (brain and nerve
      cord) during the late embryonic stage.

PMID- 14646594
TI  - Identification of amyloid beta-peptide responsive genes by cDNA microarray
      technology: involvement of RTP801 in amyloid beta-peptide toxicity.
AB  - Amyloid beta-peptide (Abeta), a causative molecule in the pathogenesis of
      Alzheimer's disease and the main component of senile plaques, is known to be
      neurotoxic in vitro and in vivo. The mechanisms involved in this Ab-mediated
      neurotoxicity are not fully understood, although there is evidence to suggest the
      involvement of oxidative stress, alterations in calcium homeostasis, and/or of
      CDK activators. Many studies have suggested that Ab may exert its toxic effect
      via the activation of transcription factors. Therefore, we investigated Ab-
      responsive genes in human neuroblastoma CHP134 cells using 3.1K human DNA
      microarrays. Among the several genes overexpressed or repressed by Ab, RTP801,
      Hi95/sestrin 2, and stanniocalcin 2 were confirmed to be Ab-mediated
      overexpression in the cells by semiquantitative RT-PCR. Transient expression of
      the sense RTP801 gene in CHP134 cells increased sensitivity to Abeta cytotoxicity
      and the expression of the antisense RTP801 gene protected the cells from the
      Abeta toxicity. These results suggest that RTP801 might play important roles in
      Abeta toxicity and the pathogenesis of Alzheimer's disease.

PMID- 14646595
TI  - High efficiency transduction of human VEGF165 into human skeletal myoblasts: in
      vitro studies.
AB  - We report the transduction of human VEGF165 gene into human myoblast and
      characterization of the transduced myoblasts for transduction and expression
      efficiency. Human myoblasts were assessed by immunostaining for desmin
      expression. A replication incompetent adenoviral vector carrying human VEGF165
      was constructed and used for transduction of myoblasts. Immunostaining of
      transduced myoblasts was used to determine transduction efficiency. Expression
      efficiency was confirmed by immunoblotting, ELISA and reverse transcription (RT)
      PCR analysis using human VEGF165 specific primers (5'-3' =
      5'ATGAACTTTCTGCTGTCTTGGGTG and 3'-5' = ACACCGCCTCGGCTTGTCACA3'. Biological
      activity of the secreted VEGF165 was determined by human umbilical vein
      endothelial cell proliferation and [H3] thymidine incorporation assays. Human
      myoblast preparation was >95% pure with 99% viability after transduction.
      Immunostaining showed >95% VEGF(165) positive myoblasts. Western blotting and
      ELISA revealed high VEGF165 expression in the transduced myoblasts. Maximum
      transduction efficiency was achieved by 8 h exposure of myoblasts to virus at
      1:1,000 ratio on three consecutive days. Concentration of VEGF165 released in the
      culture medium peaked (37 +/- 3 ng/ml) at 8 days post-transduction. Cell
      proliferation assay on human umbilical vein endothelial cells using supernatant
      from VEGF165 transduced myoblasts revealed extensive proliferation of cells which
      was suppressed in the presence of anti-human VEGF165 antibody in culture medium
      and was further confirmed by thymidine incorporation assay. The untransduced
      myoblasts secreted VEGF165 in vitro (300 +/- 50 pg/ml) that is enhanced many
      folds (37 +/- 3 ng/ml) in VEGF165 transduced myoblast as determined by ELISA.
      These studies suggest that human myoblast are potential carriers of human VEGF165
      to achieve concurrent angiomyogenesis for cardiac repair.

PMID- 14646596
TI  - Biochemical characterizations reveal different properties between CDK4/cyclin D1
      and CDK2/cyclin A.
AB  - CDK2 and CDK4 known promoter of cell cycling catalyze phosphorylation of RB
      protein. Enzyme specificity between two CDKs that work at a different cell cycle
      phase is not clearly understood. In order to define kinase properties of CDK2 and
      CDK4 in complex with cycline A or cycline D1 in relation to their respective role
      in cell cycling regulation, we examined enzymatic properties of both CDK4/cycline
      D1 and CDK2/cycline A in vitro. Association constant, Km for ATP in CDK4/cyclin
      D1 was found as 418 microM, a value unusually high whereas CDK2/cyclin A was 23
      microM, a value close to most of other regulatory protein kinases. Turnover value
      for both CDK4/cyclin D1 and CDK2/cyclin A were estimated as 3.4 and 3.9 min(-1)
      respectively. Kinetic efficiency estimation indicates far over one order
      magnitude less efficiency for CDK4/cyclin D1 than the value of CDK2/cycline A
      (9.3 pM(-1) min(-1) and 170 pM(-1) min(-1) respectively). In addition, inhibition
      of cellular CDK4 caused increase of cellular levels of ATP, even though
      inhibition of CDK2 did not change it noticeably. These data suggest cellular
      CDK4/cyclin D1 activity is tightly associated with cellular ATP concentration.
      Also, analysis of phosphorylated serine/threonine sites on RB catalyzed by
      CDK4/cyclin D1 and CDK2/cyclin A showed significant differences in their
      preference of phosphorylation sites in RB C-terminal domain. Since RB is known to
      regulate various cellular proteins by binding and this binding is controlled by
      its phosphorylation, these data shown here clearly indicate significant
      difference in their biochemical properties between CDK4/cyclin D1 and CDK2/cyclin
      A affecting regulation of cellular RB function.

PMID- 14646597
TI  - NF-kappaB is involved in the TNF-alpha induced inhibition of the differentiation
      of 3T3-L1 cells by reducing PPARgamma expression.
AB  - TNF-alpha, a trimeric cytokine, was known to inhibit differention of
      preadipocytes to adipocytes. In the present study, we investigated signal
      mediators working downstream of TNF-alpha using murine 3T3-L1 cells. TNF-alpha
      induced activation of both c-jun NH(2)-terminal kinase (JNK) and nuclear
      transcription factor-kappaB (NF-kappaB) in 3T3-L1 cells. Blockage of these two
      mediators activities by specific inhibitors, SP600125 and Ad-IkappaBalpha-SR
      restored adipogenesis differentiation suggesting their involvement in the
      inhibited differentiation of 3T3-L1 cells by TNF-alpha. Consistent with previous
      studies, peroxisome proliferator-activated receptor gamma (PPARgamma) a key
      transcriptional regulator was remarkably reduced by TNF-alpha treatment. Compared
      with adipogenesis, however, SP600125, a chemical JNK inhibitor hardly relieved
      TNF-alpha effect on PPARgamma expression whereas S32A/S36A mutant of IkappaBalpha
      considerably recovered PPARgamma expression, indicating that two signal mediators
      exploit separable main routes to achieve reduced adipogenesis. These results
      suggest that inhibition of 3T3-L1 cells differentiation by TNF-alpha is partly
      implemented through NF-kappaB and one of its downstream effectors be PPARgamma.

PMID- 14646598
TI  - CD99 type II is a determining factor for the differentiation of primitive
      neuroectodermal cells.
AB  - CD99 is a 32-kDa cell surface molecule present on thymocytes, peripheral T cells,
      many other hematopoietic stem cells and somatic cells were implicated in cell
      cell adhesion and cell-activation phenomena. Two major subtypes have been
      identified so far, designated CD99 type I and type II. We have investigated the
      correlation between the degree of neural differentiation and the expression of
      CD99 subtypes in three differentially differentiated cell lines such as CADO-ES1,
      RD-ES, and SH-N-SY5Y, in order of differentiation. In addition, we induced
      differentiation of the RD-ES cell line by N6,2'-dibutyryl-cAMP (db-cAMP). Six
      days after treatment with db-cAMP, RD-ES cell line has changed its morphology
      from uniform round cells to cells with neurites, and initially CD99 type II
      overexpressed RD-ES cells showed significant down-regulation of CD99 type II,
      whereas CD99 type I expression remained constant. When RD- ES cells were
      transfected with the cDNA encoding for CD99 type I-green fluorescence protein
      (GFP) and type II-GFP, CD99 type II transfected RD-ES cell line remained
      unchanged with morphology of undifferentiated form. Our data suggest that CD99
      type II acts as a negative regulator in the neural differentiation of precursor
      cells that might occur during nerve system development.

PMID- 14646599
TI  - Impaired phosphorylation and mis-localization of Bub1 and BubR1 are responsible
      for the defective mitotic checkpoint function in Brca2-mutant thymic lymphomas.
AB  - Breast cancer susceptibility gene, BRCA2, is a tumor suppressor and individuals
      who inherit one defected copy of BRCA2 allele experience early onset breast
      cancer or ovarian cancer accompanied by the loss of the wild type allele. Mouse
      model for Brca2 mutation shows growth retardation and paradoxical occurrence of
      thymic lymphomas. Thymic lymphomas from Brca2-mutant mice harbor mutations in
      p53, Bub1, and BubR1, which function as mitotic checkpoint proteins. Therefore,
      interplay between Brca2 and mitotic checkpoint has been suggested in the
      maintenance of genetic fidelity, although it has not been assessed whether the
      unique mutations in Bub1 and BubR1 found in Brca2-mutant mice are responsible for
      the abolishment of mitotic checkpoint function. This report demonstrates that
      Bub1 and BubR1 mutant proteins from Brca2-/- thymic lymphomas have defects in the
      phosphorylation and kinetochore localization after spindle damage. Thus, the
      mutations of Bub1 and BubR1 found in Brca2- mutant mice indeed are responsible
      for the chromosome instability in Brca2-mutated tumors.

PMID- 14646600
TI  - Real-time PCR analysis of the apoptosis related genes in ATRA treated APL
      t(15;17) patients.
AB  - All-trans retinoic acid (ATRA) treatment of the acute promyelocytic leukemia
      (APL) have subsequently resulted in cell apoptosis, but the molecular mechanism
      of this effect remains elusive. In order to understand a possible involvement of
      genes regulating apoptotic signal pathways, expression levels of bcl2, bax,
      dapk1, myc, bad, wt1, and mcl genes were analyzed during ATRA treatment in five
      APL patients with t (15;17) using Real- time PCR (LightCycler). Two samples from
      each patient were compared to each other: primary diagnostic sample and a sample
      taken at remission. Effect of the ATRA treatment was demonstrated by the
      concomitant induction of cd14 and il1beta genes in four patients. Also other
      apoptosis related genes were found down-regulated in general but especially the
      down regulated levels of wt1 and bax attract attention. Result suggested that
      ATRA dependent apoptosis of APL was under the control of both internal and
      external pathways without relationships to the amount of the blast populations.
      Ratio of bcl2 to bax may be more important for this regulation than the ratio of
      bcl2 to bad. Either bcl2 family or less known apoptosis related genes as wt1 will
      still be required to further studies in this setting.

PMID- 14646601
TI  - Comparison of oligonucleotide-microarray and serial analysis of gene expression
      (SAGE) in transcript profiling analysis of megakaryocytes derived from CD34+
      cells.
AB  - For the comprehensive analysis of transcript expression, the array-based
      hybridization analysis and the serial analysis of gene expression (SAGE) are
      commonly used platforms. The SAGE is based on a high-throughput sequencing of
      ditags derived from the transcript. DNA microarrays are a powerful tool for
      monitoring thousands of transcripts simultaneously, whereas the Genechip
      (Affimatrix microarray) technology is based on the hybridization of a single
      probe or other manufacturer's microarrays (cDNA- or oligonucleotide-microarray)
      procedures include the competitive hybridization of two probes. In this study,
      the quantitative accuracy of expression using oligonucleotide-microarray was
      determined by comparing data set from the SAGE. In previous study the microSAGE
      was performed for the megakaryocytes and non- megakaryocytes derived from human
      cord blood CD34+ cells by ex vivo expansion using thrombopoietin, and a total of
      38,909 tags representing 8,976 unique genes were obtained. On the identical RNA,
      expression profiling was also carried out using oligonucleotide-microarray (MAGIC
      II 10K chip, Macrogen). The most frequently expressed genes in human
      megakaryocytes were identified as platelet factor 1 followed by annexin A1,
      ribosomal protein S23. The majority of the 50 most highly expressed genes in the
      CD34+-derived megakaryocytes were those involved in protein synthesis, e.g.,
      ribosomal proteins. The expression level through the single channel of
      oligonucleotide-microarray and SAGE have a fairly good correlation in terms of
      absolute analyses and that the correlation is higher for the genes with higher
      expression levels.

PMID- 14646603
TI  - Adverse reactions to mirtazapine are unlikely to be serotonin toxicity.

PMID- 14646604
TI  - Mirtazapine: unable to induce serotonin toxicity?

PMID- 14646606
TI  - Possible relationship between testosterone and comorbid major depressive episode
      in male patients with schizophrenia treated with typical antipsychotic
      medications.
AB  - In this cross-sectional study, the author tested the hypothesis that serum
      testosterone levels were associated with depressive illness in chronic male
      schizophrenia patients. The subjects were 49 male inpatients meeting DSM-IV
      criteria for schizophrenia treated with typical antipsychotic medications. The
      author found that the schizophrenia patients with major depressive episodes (MDE)
      had been taking significantly higher dosages of antipsychotic medications than
      those without an MDE. Also, there was a trend for the serum testosterone
      concentration to be lower in schizophrenia patients with an MDE. It is suggested
      that we should be aware of testosterone levels when we find depression in chronic
      male schizophrenia patients, especially those treated with high-dose typical
      antipsychotic medications.

PMID- 14646607
TI  - Low doses of topiramate are effective in essential tremor: a report of three
      cases.
AB  - We here report on 3 patients with essential tremor, otherwise unresponsive to
      pharmacological treatment, who greatly benefited from low doses of topiramate (50
      mg/d). No side effects were observed and improvement was sustained during a mean
      of 7 months (range 3-12 months) follow up. Our results suggest that topiramate
      titration should be performed gradually, so as not to neglect cases responsive to
      low doses.

PMID- 14646608
TI  - Adjunctive quetiapine decreases symptoms of tardive dyskinesia in a patient
      taking risperidone.
AB  - Tardive dyskinesia is a potentially permanent and disfiguring side effect
      associated with the use of conventional, or first generation, antipsychotics.
      Quetiapine is a second generation antipsychotic with transient dopamine receptor
      occupancy, a property shared with clozapine. Quetiapine was administered to a
      patient who had persistent choreoathetoid movements that developed during
      treatment with conventional antipsychotics and remained unimproved during
      longterm treatment with risperidone. During 10 weeks of monotherapy with
      quetiapine, his Abnormal Involuntary Movement Scale score fell from 11 to 3. He
      was subsequently switched back to risperidone and his movements returned. The
      addition of quetiapine to his risperidone regimen once again resulted in a
      decrease of his tardive dyskinesia symptoms. The mechanism by which quetiapine
      improved tardive dyskinesia symptoms in this patient is not known, but
      differential treatment effects between the novel antipsychotics may exist.
      Controlled trials of quetiapine in the treatment of tardive dyskinesia should be
      pursued.

PMID- 14646609
TI  - Noradrenergic drugs for levodopa-induced dyskinesia.
AB  - Dyskinesia frequently mars the long-term therapeutic response to levodopa (LD) in
      Parkinson's disease (PD). New treatment strategies for levodopa-induced
      dyskinesia (LID) currently being investigated include some that target the
      nondopaminergic pathways. Indeed, LID in parkinsonism can be modulated by drugs
      acting on different neurotransmitters including glutamate, gamma-aminobutyric
      acid, noradrenaline, acetylcholine, serotonin, adenosine, and cholecystokinin. In
      many cases, the possibility of using specific compounds to counteract LID was
      raised by the previously shown efficacy of such compounds in the treatment of
      other types of dyskinesia. More data are now available on drugs that act on the
      noradrenergic system. Two studies have recently shown how the alpha-2
      adrenoreceptor antagonist idazoxan can significantly reduce LID in the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of parkinsonism
      and in patients with advanced PD. The experimental paper, which studied the
      antagonistic action of idazoxan on dyskinesia induced by both LD and apomorphine
      in marmosets with MPTP-induced parkinsonism, showed that the pharmacologic
      mechanisms underlying LID and apomorphine-induced dyskinesia in PD are probably
      distinct. LD, although not apomorphine-induced, dyskinesia was found to be
      influenced by adrenoreceptor antagonists. Indeed, the action of alpha-2
      adrenoreceptor antagonists may involve the blockade of the action of
      noradrenaline synthesized from LD. The hypothesis is that because dopamine
      agonists are not metabolized to noradrenaline, alpha-2 adrenoreceptor antagonists
      do not reduce dyskinesia produced by such agents. This finding is particularly
      relevant in planning clinical studies in which LD or dopamine agonist challenges
      are used to assess the potential antidyskinetic properties of new drugs. The
      clinical study assessed the effects of idazoxan on LID in 18 patients with
      advanced PD: An improvement in LID, without the reappearance of parkinsonian
      symptoms, was observed. The practical outcome of this research is that, although
      the mechanisms underlying the manifestations and the priming process for
      dyskinesia have yet to be fully elucidated, a nondopaminergic approach to therapy
      may provide an effective way of preventing, or at least limiting, the expression
      of involuntary movements in PD.

PMID- 14646610
TI  - Neutropenia as a complication of high-dose intravenous immunoglobulin therapy in
      adult patients with neuroimmunologic disorders.
AB  - To investigate clinical aspects of the neutropenia induced by high-dose
      intravenous immunoglobulin therapy (IVIG) we performed serial hematology,
      including differentiation of white blood cells (WBC), before and after 22
      instances of IVIG in 16 patients with neuroimmunologic disorders. WBC and
      neutrophils showed a significant decrease with a nadir 2 days after IVIG, but
      returned to previous values by 14 days with no treatment except in 2 cases. No
      patient showed any infectious complication. Both WBC and neutrophils were
      significantly decreased in cases without corticosteroid therapy but not in those
      with medication. In nine instances (4 with and 5 without corticosteroid
      treatment), CD11b and CD16 on neutrophils were investigated using flow cytometry.
      In 3 of 5 instances without corticosteroid treatment the expression of CD11b was
      decreased after IVIG, while no change was detected in CD16. There was no
      difference in either CD11b or CD16 between before and after IVIG in instances
      with corticosteroid therapy. Neutropenia commonly and transiently develops just
      after IVIG, and can be prevented by corticosteroid pretreatment. Circulating
      neutrophils might bind to the vascular wall mainly with the involvement of CD11b
      and migrate into a storage pool, resulting in an apparent neutropenia after IVIG.

PMID- 14646611
TI  - Prevalence and characteristics of subjective akathisia, objective akathisia, and
      mixed akathisia in chronic schizophrenic subjects.
AB  - Akathisia is a complex syndrome that is characterized by subjective inner
      restlessness and objective motor manifestations, and it can be classified into
      several subtypes. The purpose of this study was to examine the prevalence of
      subjective akathisia, objective akathisia, and mixed akathisia, and to evaluate
      their relationships with other drug-induced movement disorders, in chronic
      schizophrenic subjects treated with antipsychotics. One hundred and forty-two in
      patients were assessed for akathisia, drug-induced parkinsonism, and tardive
      dyskinesia. The subtypes of akathisia were specified according to the Barnes
      Akathisia Rating Scale. Drug-induced parkinsonism and tardive dyskinesia were
      assessed using the Simpson-Angus Scale and the Abnormal Involuntary Movement
      Scale, respectively. The prevalence of subjective, objective, and mixed akathisia
      was 11.3%, 6.3%, and 16.9%, respectively. Regarding concurrence rates of
      akathisia subtypes and other extrapyramidal syndromes, the comorbidity rates of
      mixed akathisia with parkinsonism and tardive dyskinesia were higher. In
      conclusion, the present study presented the prevalence of subjective, objective,
      and mixed akathisia among hospitalized schizophrenic subjects. Mixed akathisia
      showed an association with parkinsonism and tardive dyskinesia, suggesting a
      common vulnerability involved in these drug-induced movement disorders. Further
      studies are required to elucidate more detailed clinical characteristics of each
      subtype of akathisia.

PMID- 14646612
TI  - Effects of rivastigmine on cognitive function and quality of life in patients
      with schizophrenia.
AB  - We aimed to determine whether the cholinesterase inhibitor rivastigmine, an
      inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), would
      improve quality of life and cognitive function in 16 clinically stable subjects
      affected by schizophrenia in the residual phase. Study subjects began
      rivastigmine treatment at a dose of 1.5 mg bid. This dose was escalated at
      monthly intervals in increments of 1.5 mg bid to a maximum of 6 mg bid. All
      subjects were followed for 12 months. Quality of life was assessed using the
      Satisfaction with Life Domains Scale (SLDS, a self-report scale containing 10
      "satisfaction" items); cognitive function, attentional function, and aspects of
      learning and memory were evaluated using common neuropsychological tests.
      Psychopathology was evaluated by means of the Brief Psychiatric Rating Scale
      (BPRS). Rivastigmine treatment resulted in significant improvements in quality of
      life, which were paralleled by significant improvements in cognitive function,
      learning and memory, and trends for improvement in attention. The BPRS factor
      "anergia" showed significant improvement, while low baseline scores in other
      psychotic factors did not permit further improvements. There were no reports of
      nausea or vomiting. In conclusion, rivastigmine significantly improved quality of
      life in subjects with schizophrenia. These benefits may relate to the drug's
      effects on cognitive deficits and negative symptoms associated with the
      condition.

PMID- 14646613
TI  - Pharmacokinetics of etilevodopa compared to levodopa in patients with Parkinson's
      disease: an open-label, randomized, crossover study.
AB  - "Dose failures" and "delayed on" phenomena following an intake of levodopa dose
      in patients with Parkinson's disease (PD) with motor fluctuations may be caused
      by stagnation of poorly soluble levodopa in the atonic stomach. Etilevodopa is a
      unique, highly soluble prodrug of levodopa. When ingested, etilevodopa is more
      readily dissolved in the stomach than levodopa. It passes unchanged through the
      stomach to the duodenum, where it is rapidly hydrolyzed by local esterases and
      rapidly absorbed as levodopa. To compare the pharmacokinetics of three different
      modes of etilevodopa/carbidopa administration with standard levodopa/carbidopa
      tablets in fluctuating PD patients, 29 patients with PD and response fluctuations
      were enrolled in an open-label, randomized, four-way crossover study of single
      doses of 4 treatments: swallowed etilevodopa/carbidopa tablets,
      etilevodopa/carbidopa tablets dissolved in water, etilevodopa oral solution with
      carbidopa tablets, and standard levodopa/carbidopa tablets. To measure the
      maximal concentration (Cmax), time to Cmax (tmax), and area under the curve (AUC)
      of plasma levodopa, etilevodopa, and carbidopa, blood samples were drawn before
      drug administration and at intervals up to 240 minutes thereafter. Plasma
      levodopa tmax was significantly shorter with all three modes of administration of
      etilevodopa (mean of about 30 minutes) than with levodopa treatment (mean of 54
      minutes). During the first 45 minutes after drug ingestion, plasma levodopa AUC
      was significantly greater after etilevodopa administration than after levodopa
      administration. Levodopa AUC for 0 to 1 hour and 0 to 2 hours were also
      significantly greater following administration of etilevodopa/carbidopa swallowed
      tablets than following administration of levodopa/carbidopa tablets. Mean
      levodopa Cmax was in the range 2.3 to 2.7 microg/mL for all treatments. Levodopa
      Cmax was significantly greater following treatment with etilevodopa swallowed
      tablets than with levodopa tablets. Etilevodopa/carbidopa was well tolerated,
      with a safety profile comparable to that of levodopa/carbidopa. The shorter
      levodopa tmax observed with etilevodopa potentially translates to a shorter time
      to "on". Clinical trials with etilevodopa/carbidopa tablets should be carried out
      in PD patients with response fluctuations such as "delayed on" and "dose
      failures".

PMID- 14646614
TI  - Carbamazepine, clonazepam and focal reflex proprioceptive seizures.
AB  - We studied a 34-year-old man with focal tonic-clonic seizures sometimes elicited
      by some active postures of the right hand and evolving at times to secondary
      generalization. Treatment with carbamazepine (CBZ) in combination with parenteral
      diazepam induced both a dramatic increase of focal reflex proprioceptive seizures
      and choreoathetoid dyskinesias in the affected hand. CBZ was withdrawn and
      clonazepam (CZP) given 2 mg daily, with complete relief of seizures and
      choreoathetoid dyskinesias. CZP had a suppressive effect on seizures for over 15
      years, without development of tolerance.

PMID- 14646615
TI  - Biochemical characterization of a new melanoma model--the minipig MeLiM strain.
AB  - Hereditary minipig melanomas, which have many histopathological and other
      features in common with their human counterparts, have recently become preferred
      melanoma models. The MeLiM (Melanoma-bearing Libechov Minipig) strain was
      selected by partial inbreeding. A high tumour incidence and malignant behaviour
      on the one hand together with the occurrence of spontaneous regression and high
      susceptibility to the devitalization technique as a new strategy in melanoma
      therapy, make the MeLiM strain a superior melanoma model to other hereditary
      swine melanomas. Biochemical analyses of the tumours revealed: (i) a high
      concentration of eumelanin and low concentration of phaeomelanin in melanoma
      cells, which makes the probability of photochemical regression of MeLiM melanomas
      negligible; (ii) an extremely high level of melanosomes (almost half of the
      melanoma dry weight), which suggests a high differentiation of the MeLiM melanoma
      and is consistent with its mechanical rigidity; (iii) the presence of typical
      melanoma enzymes--tyrosinase, alpha-mannosidase and gamma-glutamyltransferase;
      and (iv) in the tumours regressing as a consequence of devitalization treatment,
      alpha-mannosidase activity was reduced and tyrosinase activity approached the
      detection threshold, which is in accordance with the substitution of melanoma
      tissue for connective tissue in devitalized tumours observed histologically.
      (Immuno)histochemical comparisons (based on dopaoxidase reaction, S100 and HMB-45
      reactivities) of the skin from white and pigmented minipigs revealed the absence
      of melanocytes in white skin. This is the first direct evidence supporting a
      possible explanation for the absence of melanoma in white minipigs. The
      similarities and dissimilarities of the MeLiM model compared with human melanoma
      are highlighted.

PMID- 14646616
TI  - Vitamin C downregulates interleukin-18 production by increasing reactive oxygen
      intermediate and mitogen-activated protein kinase signalling in B16F10 murine
      melanoma cells.
AB  - We recently reported that interleukin-18 (IL-18) is highly expressed in malignant
      skin tumours such as melanomas, and may play a key role in the malignancy of such
      tumours. This study was designed to investigate the mechanisms of IL-18
      regulation by vitamin C in B16F10 murine melanoma cells. Cells were treated with
      vitamin C, and the expression of IL-18 was measured by reverse transcription
      polymerase chain reaction and intracellular flow cytometry analysis. Decreased IL
      18 production and a significant reduction in IL-18 mRNA transcript were detected
      in cells treated with vitamin C. The effect of vitamin C treatment was blocked by
      the antioxidant N-acetyl-L-cysteine, suggesting that vitamin C affects IL-18
      expression by up-regulating intracellular reactive oxygen intermediate (ROI)
      levels. To investigate whether the mitogen-activated protein kinase (MAPK)
      signalling pathway is involved in the downregulation of IL-18 production, cells
      were pretreated with SB203580, an inhibitor of p38 MAPK, prior to the addition of
      vitamin C. This pretreatment blocked the decrease in IL-18 production. However,
      vitamin C treatment enhanced the expression of phosphorylated p38 MAPK. Taken
      together, we conclude that vitamin C increases intracellular ROI levels, and
      regulates IL-18 production through the MAPK signalling pathway.

PMID- 14646617
TI  - Expression and regulation of phospholipase D isoenzymes in human melanoma cells
      and primary melanocytes.
AB  - Phospholipase D (PLD) is a highly regulated enzyme involved in lipid-mediated
      signal transduction processes affecting vesicular trafficking and cytoskeletal
      reorganization. It is regulated by protein kinase C, adenosine diphosphate (ADP)
      ribosylation factors and Rho family proteins, and both protein kinase C and Rho
      family proteins have been implicated in the metastatic potential of melanoma. We
      analysed PLD in four human melanoma cell lines and in primary human melanocytes.
      Melanoma cell lines showed phosphatidylcholine-hydrolysing, phosphatidylinositol
      4,5-bisphosphate-dependent PLD activity, which was activated by phorbol ester and
      a non-hydrolysable guanosine triphosphate (GTP) analogue in a dose-dependent and
      synergistic manner, whereas primary melanocytes exhibited only low PLD activity
      compared with the melanoma cell lines. As determined by reverse transcription
      polymerase chain reaction, both splicing variants of PLD1, PLD1a and PLD1b, and
      the isoenzyme PLD2, are expressed in melanoma cells and melanocytes. Western blot
      analysis showed that PLD1 expression was low in primary melanocytes in contrast
      to melanoma cells, which is in agreement with our finding of low activity.
      Interestingly, Rho protein mRNA was elevated in all melanoma cell lines. We
      conclude that in human melanoma cells, the PLD activity that is stimulated by
      phorbol ester requires ADP-ribosylation factor, protein kinase C and Rho proteins
      for full activity, and most probably represents the isoenzyme PLD1.

PMID- 14646618
TI  - Lead acetate genotoxicity on human melanoma cells in vitro.
AB  - In this study, chromosomal damage induced in vitro by lead acetate in human
      melanoma cells (B-Mel) was evaluated using the cytokinesis-blocked micronucleus
      assay and sister chromatid exchange (SCE) analysis. Lead acetate (10-6, 10-5 and
      10-3 mM) induced micronuclei and SCE formation in a dose-dependent manner.
      Treated cells showed a decrease in cell viability but not concomitant cell death
      by apoptosis (lead acetate failed to induce internucleosomal DNA fragmentation at
      any of the doses tested). One important observation emerging from this study was
      that low-level lead exposure in vitro is able to induce significant cytogenetic
      damage in human melanoma cells, indicating an increased sensitivity of B-Mel
      cells to lead acetate.

PMID- 14646619
TI  - A novel L94Q mutation in the CDKN2A gene in a melanoma kindred.
AB  - About 10% of melanoma cases have clinical factors indicative of hereditary
      cancer. CDKN2A is a major melanoma susceptibility gene in familial malignant
      melanoma. In this study a novel L94Q missense mutation of the CDKN2A gene is
      described in a melanoma kindred with two affected second-degree family members.
      To detect the mutation, polymerase chain reaction (PCR) amplification methods and
      direct sequencing were used. The presence of the mutation was confirmed by
      restriction fragment length polymorphism analysis after digestion of the PCR
      amplicons with the restriction endonuclease BspMI. The penetrance of the novel
      mutation was shown to be incomplete. Functional importance of the mutation was
      assumed from the protein p16 structure.

PMID- 14646620
TI  - Mutation analysis of candidate genes in melanoma-prone families: evidence of
      different pathogenetic mechanisms at chromosome 9P21.
AB  - Putative tumour suppressor genes CDKN2A and CDKN2B (on chromosome 9p21) and
      CDKN2A-interacting cell growth regulatory genes CDK4 and Id-1 have been
      demonstrated to be involved in the pathogenesis of malignant melanoma (MM).
      Mutation analysis of these candidate genes was performed in MM families from
      southern Italy with three or more affected members or two affected members and
      one or more relative with histologically diagnosed atypical naevus. Two CDKN2A
      mutations, Arg24Pro and 1-292 G>A, were observed in two (15%) families; except
      for CDKN2A and Id-1 polymorphisms, no sequence variations were detected in the
      remaining genes. Screening among 119 sporadic MM cases revealed two additional
      CDKN2A mutations at very low prevalences. Identification of a large shared
      haplotype at 9p21 in some MM families negative for CDKN germline mutations
      suggests that other CDKN-inactivating mechanisms may be responsible for MM
      predisposition or, alternatively, additional susceptibility gene(s) may be
      present on chromosome 9p21. Fluorescence in situ hybridization analysis of a
      subset of MM tissue sections seemed to indicate that the D9S171 locus may be
      involved in MM pathogenesis.

PMID- 14646621
TI  - Use of multiple cytometric markers improves discrimination between benign and
      malignant melanocytic lesions: a study of DNA microdensitometry, karyometry,
      argyrophilic staining of nucleolar organizer regions and MIB1-Ki67
      immunoreactivity.
AB  - Confident separation of benign naevi and malignant melanoma can sometimes be very
      difficult using conventional microscopy. This study evaluated the combined
      diagnostic abilities of multiple cytometric markers in separating various types
      of naevi from melanomas. The lesions studied included 27 benign compound naevi,
      20 dysplastic naevi, 10 Spitz naevi and 24 melanomas. The cytometric features
      investigated were: (i) nuclear DNA content and chromatin compactness, measured by
      video imaged DNA microdensitometry; (ii) nuclear morphology, measured by nuclear
      morphometry (karyometry); (iii) transcriptional activity of nucleolar organizer
      regions, measured as the number and size of argyrophilic staining of nucleolar
      organizer regions (AgNORs); and (iv) cellular proliferative activity detected by
      quantifying the immunoreactivity of MIB1-Ki67 antigen. These variables were
      evaluated in the superficial, middle and deep zones of each lesion. Using
      multivariate discriminant analysis, a total diagnostic effectiveness of 97% could
      be achieved in separating the benign and malignant melanocytic lesions by co
      evaluating variables for DNA microdensitometry, karyometry and AgNORs. A
      diagnostic effectiveness of 100% could be achieved if further co-evaluation with
      MIB1-Ki67 immunoreactivity was performed. Our study suggests that co-evaluation
      of multiple cytometric markers can improve the diagnostic abilities of individual
      techniques in separating benign naevi from malignant melanomas. This may be of
      particular significance in the diagnosis of melanocytic lesions whose biological
      behaviour cannot be confidently predicted by their histological features using
      conventional microscopy.

PMID- 14646622
TI  - Evaluation of the serum L-dopa/L-tyrosine ratio as a melanoma marker.
AB  - A wide range of molecules have been investigated as tumour markers in melanoma,
      most of which are not suitable for use by clinical oncologists for the detection
      of fast and unpredictable metastatic dissemination. We have already shown that
      the serum L-dopa/L-tyrosine ratio (an index of tyrosinase functional activity)
      correlates with the tumour burden and in some cases predicted disease progression
      in metastatic melanoma patients. We examined the potential value of this ratio
      for the follow-up, therapy monitoring and prognosis in melanoma compared with a
      reference marker (S100B, a melanoma-associated antigen). Sixty melanoma patients
      (24 stage I-II, 18 stage III, 18 stage IV, American Joint Committee on Cancer
      staging) were entered into the study, sampled two to eight times (before and
      after therapy) and were followed for up to 30 months. Serum L-dopa and L-tyrosine
      were determined by high performance liquid chromatography and S100B by an
      immunoluminometric assay. In stage III patients with elevated marker
      concentration, lymph node dissection decreased the S100B level (from 0.27 to <
      0.13 microg/l, P=0.008), but not the L-dopa/L-tyrosine ratio. Chemotherapy
      decreased the L-dopa/L-tyrosine ratio by 38% (P =0.04) and the S100B level by 45%
      (P = 0.02) in stage IV responders. During follow-up, patients with marker levels
      within normal limits (n=19) had stable disease, except for two stage II patients.
      In patients with progressive disease (n=20), an increase in one or both markers
      was observed. Stage IV patients with high L-Dopa/L-Tyrosine ratio (above 20 x 10
      5) at inclusion had shorter survival (3 months), while patients with low levels
      had longer survival (15 months). Levels of S100B had no impact on survival, as
      all stage IV patients (with levels below or above 0.38 microg/l) had the same
      survival (5 months). The serum L-dopa/L-tyrosine ratio may be influenced by
      successful therapy and levels at inclusion may correlate with prognosis in stage
      IV patients. Levels of these two markers in other biological fluids such as
      cerebrospinal fluid and tumour exudates may be useful diagnostically and
      prognostically in difficult cases.

PMID- 14646623
TI  - Primary malignant melanoma of the oesophagus: a clinical and pathological study
      with emphasis on the immunophenotype of the tumours for melanocyte
      differentiation markers and cancer/testis antigens.
AB  - SUMMARY: Primary malignant melanomas of the oesophageal squamous mucosa are
      exceedingly rare. We present here the clinical and pathological findings of 10
      patients (mean age 64 years) with primary oesophageal melanoma, with emphasis on
      the immunophenotype of the tumours. The majority of melanomas were located in the
      mid to distal oesophagus and were large (mean tumour size at the time of
      diagnosis 6.2 cm; mean depth of invasion 1.86 cm). All but two of the melanomas
      were associated with an extensive in situ component. Half of the tumours were
      amelanotic. The histological spectrum was wide, including appearances mimicking
      lymphoma, poorly differentiated adenocarcinoma or sarcoma. Immunohistochemical
      studies were performed on six tumours using monoclonal antibodies (MAb) to S100
      protein, tyrosinase (MAb T311), Melan-A (MAb A103), and gp100 (MAb HMB-45), as
      well as antibodies to five cancer/testis (CT) antigens (MAb CT7-33 to CT7/MAGE
      C1, MAb ESO121 to NY-ESO-1, MAb 57B to MAGE-A4, MAb MA454 to MAGE-A1, and MAb
      M3H67 to MAGE-A3). Seven patients had metastatic disease at the time of
      presentation. All but one patient underwent resection of the tumour with negative
      surgical margins. Survival was poor, with a mean survival of 19.8 months. One
      patient, however, whose tumour was limited to the submucosa, is still alive 108
      months post-oesophagectomy. All six melanomas examined by immunohistochemistry
      were positive for all the melanocyte differentiation markers tested. In addition,
      they were all positive for CT antigens, with MA454 being the most commonly found,
      suggesting that CT antigens may be a promising immunotherapeutic target for
      oesophageal melanomas.

PMID- 14646624
TI  - Synthesis and selective in vitro anti-melanoma effect of enantiomeric alpha
      methyl- and alpha-ethyl-4-S-cysteaminylphenol.
AB  - Melanogenesis provides a unique target for the development of antitumour agents
      specific for malignant melanoma. Among the anti-melanoma compounds we have
      examined, 4-S-cysteaminylphenol (4-S-CAP), a phenolic amine, was found to have
      the most promising anti-melanoma effects. To further improve its efficacy as an
      anti-melanoma agent, we synthesized the R- and S-enantiomers (99% enantiomer
      excess) of alpha-methyl- 4-S-cysteaminylphenol (alpha-Me-4-S-CAP) and alpha-ethyl
      4-S-cysteaminylphenol (alpha-Et-4-S-CAP) by coupling 4-hydroxythiophenol with
      the oxazolines obtained from the (R)- and (S)-enantiomers of 2-amino-1-propanol
      and 2-amino-1-butanol, respectively. The enantiomers of alpha-Me-4-S-CAP and
      alpha-Et-4-S-CAP were found to be better substrates for tyrosinase than the
      natural substrate, L-tyrosine. In vitro experiments showed that all four
      enantiomers were highly cytotoxic to pigmented B16-F1 melanoma cells, the effect
      being 70-fold and 160-fold greater than that on non-pigmented B16-G4F melanoma
      cells and 3T3 fibroblasts, respectively. The cytotoxic effect against B16-F1
      cells was completely inhibited by phenylthiourea, a tyrosinase inhibitor, or by N
      acetyl-L-cysteine, which increases the intracellular reduced glutathione (GSH)
      level. 4-S-CAP and the enantiomers were taken up into B16-F1 cells at comparable
      rates, but showed varying rates of GSH depletion that were inversely correlated
      to the cytotoxicity. These results suggest that the use of enantiomers would
      increase the efficacy of tyrosinase-dependent cytotoxic phenols.

PMID- 14646625
TI  - Treatment of locoregional metastases of malignant melanomas with radiotherapy and
      intralesional beta-interferon injection.
AB  - Intralesional injection of beta-interferon can lead to remission of metastatic
      melanomas. Simultaneous radiotherapy may augment the effect of these injections.
      The effect of intralesional beta-interferon injections combined with radiotherapy
      was examined in patients with metastatic malignant melanoma. A total of 20
      patients with inoperable, incapacitating and disfiguring malignant melanoma
      metastases were treated with simultaneous external beam radiotherapy (electrons
      and/or photons) and intralesional injection of beta-interferon. The total
      radiation dosage ranged from 40-50 Gy, fractionated as 1.8 Gy five times per
      week. beta-Interferon (Fiblaferon) 3-5 million units per injection was
      administered three times weekly until symptoms disappeared or until termination
      of therapy. One patient was treated with beta-interferon alone; the area
      harbouring the tumour had been previously irradiated. Five patients treated in
      this way showed partial remission after combined therapy and 12 showed complete
      remission, with permanent regression of metastases. The latter group included
      five patients with lengthy survival times, including one patient who has been
      free of symptoms for 7 years following treatment. Injected metastases showed
      complete regression in the patient who was treated exclusively with beta
      interferon post-irradiation. In conclusion, combined treatment with radiotherapy
      and intratumoral injection of beta-interferon controlled local tumour growth in
      inoperable metastatic malignant melanomas.

PMID- 14646626
TI  - Phase II randomized trial of cisplatin and WR-2721 versus cisplatin alone for
      metastatic melanoma: an Eastern Cooperative Oncology Group Study (E1686).
AB  - This study was designed to evaluate the toxicity and efficacy of cisplatin and WR
      2721 in contrast to cisplatin alone for the therapy of measurable metastatic
      melanoma. Ninety-four patients with metastatic melanoma were randomized to
      receive either cisplatin at a dose of 150 mg/m2 and WR-2721 at a dose of 910
      mg/m2, or cisplatin alone at a dose of 120 mg/m2. WR-2721 did not mitigate the
      toxic effects of cisplatin, and toxicity was increased in the WR-2721 plus
      cisplatin arm compared with cisplatin alone. For patients receiving cisplatin
      alone, the response rate was 16.3%; for those receiving cisplatin plus WR-2721,
      the response rate was 23.3%. The duration of response was 7.3 months. Median
      survival in the intent-to-treat analysis was 7.58 months. The study was
      terminated after accrual of 94 patients, with inadequate power to define an
      effect of WR-2721 on the duration of response and survival. In conclusion,
      cisplatin with WR-2721 showed an improved response rate over cisplatin alone. The
      lack of improved duration of response or impact on survival may be the result of
      the limited improvement of efficacy with the higher dosage of cisplatin in
      conjunction with WR-2721, or the limited number of patients accrued to this
      study. These factors, coupled with the failure of the combination to diminish
      toxicity, dampen enthusiasm for this combination.

PMID- 14646627
TI  - Proteomics in uveal melanoma.
AB  - A new tool in the search for tumour markers is proteomic technology. Proteomics
      (or protein profiling) is the study of the proteome, the protein complement of
      the genome. The advantage of this technique in comparison with genomics is that
      the actual protein production can be measured. Gene microarrays determine levels
      of mRNA but do not necessarily predict the level of the corresponding proteins in
      a cell. In this study, we evaluated the use of proteomics in the aqueous humour
      of uveal melanoma patients compared with control patients using the surface
      enhanced laser desorption ionization time-of-flight technique. The protein mass
      spectra of aqueous humours from 24 uveal melanoma eyes were compared with 24
      control eyes using a strong anion exchange surface protein chip array. On the
      basis of two proteins (4543.43 and 6853.30 kDa), the aqueous humour of melanoma
      eyes and control eyes could be distinguished in 89% of cases. Therefore,
      proteomic evaluation might be helpful in finding diagnostic markers for uveal
      melanoma patients.

PMID- 14646628
TI  - Low positive predictive value of ABCD-E rule for dermatoscopy of small
      melanocytic naevi.

PMID- 14646629
TI  - Atypical dermatofibroma-like pattern of a melanoma on dermoscopy.

PMID- 14646630
TI  - Cutaneous zosteriform melanoma metastases arising after herpes zoster infection:
      a case report and review of the literature.

PMID- 14646631
TI  - Outbreak of syphilis among men who have sex with men in Houston, Texas.

PMID- 14646632
TI  - Treating asymptomatic sexually transmitted diseases at anonymous HIV counseling
      and testing sites.

PMID- 14646633
TI  - Seroprevalence of HIV among sexually transmitted infections clinic attenders
      voluntarily tested for HIV in Barcelona, 1998-2001.
AB  - BACKGROUND: Spain has been the European country most affected by the AIDS
      epidemic, and sexual transmission now accounts for the majority of cases of HIV.
      GOAL: The goal was to describe HIV prevalence and risk profiles among people
      tested for HIV in Barcelona in 1998 to 2001. STUDY DESIGN: We studied cross
      sectional HIV surveys among sexually transmitted infection clinic attenders. We
      performed quantification of risk factors for HIV infection through odds ratios
      (ORs) and logistic regression. RESULTS: The prevalence of HIV among the 4993
      persons tested was 1.8% (95% confidence interval, 1.5-2.2) without significant
      changes across the years. HIV prevalence in homo-/bisexual men was higher
      (P<0.001) at 4.8% than heterosexuals. Although men aged older than 30 compared
      with those younger were at increased risk, 2.56), young homosexual men were at
      higher risk (OR, 17.84) to be infected than young heterosexuals. CONCLUSION: HIV
      prevalences were relatively low among all heterosexuals, but much higher among
      homosexual and bisexual men. The potential exists for ongoing sexual HIV
      transmission among homo-/bisexual men in Barcelona.

PMID- 14646634
TI  - Prevalence of Chlamydia trachomatis infections and specimen collection preference
      among women, using self-collected vaginal swabs in community settings.
AB  - BACKGROUND: Chlamydia trachomatis is a common, often asymptomatic sexually
      transmitted infection. GOAL: The goal was to estimate the prevalence and
      predictors of C. trachomatis among young women using self-collected vaginal
      swabs, and the preferences of women and physicians for self-testing. STUDY
      DESIGN: A total of 514 attendees of university/college health clinics, adolescent
      birth control clinics, centers providing health services to homeless youth and
      adults (street health centers), a sexually transmitted diseases clinic, and
      family practices were tested by ligase chain reaction. Preference for self-
      versus provider-testing was examined. RESULTS: Prevalence was 6.0% and was
      highest (18.2%) in the street health centers. In multivariate analysis, only
      recent contact with someone with C. trachomatis infection was significantly
      associated with infection (odds ratio, 7.1; 95% confidence interval, 2.5-20.0).
      Most women (54.2%; 256 of 472) preferred self-sampling compared with physician
      sampling (15.9%; 75 of 472). The majority of physicians (75.0%; 9 of 12) reported
      at the start and end of the study that they would use vaginal swab self-sampling
      if available. CONCLUSIONS: Prevalence of infection in young women attending
      homeless youth organizations was high. Self-sampling was acceptable and could
      facilitate screening in high-risk women who do not regularly access health
      services.

PMID- 14646635
TI  - Screening for Neisseria gonorrhoeae and Chlamydia trachomatis in men who have sex
      with men at male-only saunas.
AB  - BACKGROUND AND OBJECTIVES: In response to increases in sexually transmissible
      infections (STI) and HIV infection rates among men who have sex with men (MSM),
      the current study aimed to investigate the feasibility of a screening program at
      male-only saunas in Melbourne, Australia. GOAL: The goal was to determine (1) the
      participation rate, and the proportion whom obtain test results; (2) the
      prevalence of gonorrhea and chlamydia; and (3) to evaluate risk factors for STI
      acquisition. STUDY DESIGN: We used a cross-sectional design. Pharyngeal, rectal,
      and urethral specimens were collected from participants, and tested for Chlamydia
      trachomatis and Neisseria gonorrhoeae by polymerase chain reaction (PCR).
      RESULTS: There was a participation rate of 24% (n=521), and 70% obtained their
      test results. The infection rate in those who failed to collect their results was
      no different than those seeking theirs. The proportion of participants with PCR
      detected gonorrhea and/or chlamydia infection was high, 10.7%. The presence of
      infection was associated with seeking sexual health care in the last year.
      CONCLUSION: The high prevalence rate of gonorrhea and chlamydia supports the
      concept of a screening program in Melbourne male-only saunas. The low
      participation rate has highlighted the need to consider alternative methods for
      making contact with men in the saunas or offering incentives to participate in
      future screening programs. Although anonymous participation encouraged
      participation for some men, future programs should attempt to obtain contact
      details for follow up of positive test results.

PMID- 14646636
TI  - Prevalence and risk factors for infection with herpes simplex virus type-1 and -2
      among lesbians.
AB  - BACKGROUND AND OBJECTIVES: Sexual transmission of bacterial and viral sexually
      transmitted disease has been reported between women. No data are available on
      seroprevalence of herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) among
      lesbians. GOAL: The goal was to define prevalence of infection with HSV-1 and HSV
      2 among lesbians, and associated risk factors. STUDY DESIGN: Women who reported
      sex with another woman in the preceding year were eligible. Medical and sexual
      histories were obtained. Serum was tested for HSV-1 and HSV-2 antibodies using
      Western Blot assay. RESULTS: Among 392 subjects, antibodies to HSV-1 were
      detected in 46% and to HSV-2 in 8%. Increasing age predicted higher
      seroprevalence to both HSV types, and HSV-2 seropositivity was associated with a
      history of male partner with genital herpes. Of 78 women reporting no prior sex
      with men, 3% were HSV-2-seropositive. Most HSV-2-seropositive subjects (71%)
      reported no history of genital herpes. HSV-1 seroprevalence increased
      significantly with an increasing number of female sex partners. CONCLUSIONS: HSV
      2 infection occurs in nearly 1 in 10 lesbians and is not predicted by report of
      sex with men or sexual identity. Most lesbians infected with HSV-2 are not aware
      of their infection. Sexual transmission of HSV-1 may occur more frequently among
      lesbians than among heterosexual women.

PMID- 14646637
TI  - Trends of chromosomally mediated antimicrobial resistance in Neisseria
      gonorrhoeae in Canada: 1994-1999.
AB  - BACKGROUND AND OBJECTIVES: We monitored the trends of chromosomally mediated
      resistant Neisseria gonorrhoeae (CMRNG) in Canada. Chromosomally resistant N.
      gonorrhoeae (CMRNG) were defined as having resistance to 3 antibiotics:
      penicillin (minimum inhibitory concentration [MIC] > or =2.0 mg/L), tetracycline
      (MIC > or =2.0 mg/L and < or =8.0 mg/L), and erythromycin (MIC > or =2.0 mg/L).
      GOAL: The goal was to provide surveillance data for public health interventions
      for the control of gonococcal infections. STUDY DESIGN: Antibiotic susceptibility
      tests were performed on N. gonorrhoeae isolates obtained from 1994 to 1999 in
      Canada. Strains were further characterized by auxotype (A), serovar (S), and
      plasmid profile (P). RESULTS: Between 1994 and 1999, 19.2% of strains were CMRNG,
      12.9% had a combined resistance to tetracycline and erythromycin, and 4.7% were
      resistant to tetracycline. The incidence of ciprofloxacin resistance and
      azithromycin resistance was 2.3% and 0.8%, respectively. CONCLUSION: This survey
      of N. gonorrhoeae provides strain characterization data and temporal trends of
      strains in the Canadian population. CMRNG strains are on the rise, and the
      continual monitoring and characterization of these strains is important for the
      evaluation of current recommended antibiotic therapies used in Canada.

PMID- 14646638
TI  - Prevalence and high rate of asymptomatic infection of Chlamydia trachomatis in
      male college Reserve Officer Training Corps cadets.
AB  - BACKGROUND: Prevalence of Chlamydia trachomatis and risk factors for infection
      are not well described in male college students enrolled in the Reserved Officer
      Training Corps (ROTC). GOAL: The goal was to determine prevalence of C.
      trachomatis infection, percentage of asymptomatic infections, and risk factors
      for infection in a population of male college ROTC students. STUDY DESIGN: We
      conducted a prevalence survey of C. trachomatis infection and risk factors using
      urine ligase chain reaction and questionnaire. Participants were 1443 ROTC male
      college cadets at Ft. Lewis, Washington, from June to July 2001. RESULTS:
      Prevalence of C. trachomatis infection was 31 of 1252 (2.48%); 93.6% of the
      infections were asymptomatic. Black race, exposure to a partner with a prior
      sexually transmitted disease, and self-reported symptoms were significant risk
      factors. CONCLUSIONS: The prominence of asymptomatic infection in a male
      population with comparatively low prevalence suggests that risk factor rather
      than clinically based screening could be beneficial in this population.

PMID- 14646639
TI  - Sexually transmitted infection/HIV laboratory testing in resource-limited
      countries: steps to improve use effective testing and to ensure diagnostic
      capacity.

PMID- 14646640
TI  - Correlates of recent unprotected anal sex among men having sex with men attending
      a large sex resort in the South.
AB  - BACKGROUND: Published studies have not investigated sexually transmitted disease
      associated risk behaviors among men who have sex with men (MSM) attending U.S.
      sex resorts. GOAL: We conducted an exploratory study to identify demographic and
      behavioral correlates of recently engaging in unprotected anal sex (UAS) among
      MSM attending a sex resort in the southern United States. STUDY DESIGN: A cross
      sectional survey of 150 men. RESULTS: In multivariate analyses, men were more
      likely to practice risky sex if they also recently engaged in the practices of
      having group sex (adjusted odds ratio [AOR], 3.0), rimming (AOR, 2.0), or if they
      used public restrooms to meet potential sex partners (AOR, 2.6). UAS was also
      more likely among men vaccinated against hepatitis B (AOR, 1.9). Men who reported
      having primary partners and men who reported being HIV-positive were no less
      likely than other men in the sample to report recent UAS. CONCLUSION: Sex resorts
      can be an important venue for sexually transmitted disease and HIV prevention
      among MSM. Tailored prevention messages could be warranted for men who report
      group sex, rimming, meeting partners in public restrooms, or being vaccinated
      against hepatitis B.

PMID- 14646641
TI  - Hepatitis B virus infection risk factors and immunity among sexually transmitted
      disease clinic clients.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis B virus (HBV) infection is a sexually
      transmitted infection that can be prevented with hepatitis B vaccination. GOAL:
      The goal was to determine prevalence and risk factors for HBV infection and
      immunity among sexually transmitted disease (STD) clinic clients. STUDY DESIGN:
      In this cross-sectional study, consenting adult STD clinic clients were
      interviewed regarding HBV risk factors and vaccination history, and blood was
      drawn for HBV serologic testing. RESULTS: Of the 682 participants, 154 (22.6%)
      had antibody to hepatitis B core antigen, indicating previous infection, and 64
      (9.4%) had only antibody to hepatitis B surface antigen, indicating immunity as a
      result of hepatitis B vaccination. Only 130 (19.1%) of all participants reported
      receiving at least one dose of hepatitis B vaccine. CONCLUSION: The majority of
      clients were susceptible to HBV, were at high risk for HBV infection, and would
      benefit from hepatitis B vaccination.

PMID- 14646643
TI  - Incidence and severity of short-term complications after breast augmentation:
      results from a nationwide breast implant registry.
AB  - The frequency and severity of local complications remain the primary safety
      issues with silicone breast implants. The Danish Registry for Plastic Surgery of
      the Breast (DPB), established in 1999, prospectively collects pre-, peri- and
      postoperative information regarding Danish women undergoing breast augmentation.
      Through DPB, we conducted a prospective follow-up study of short-term local
      complications among 1090 women who underwent cosmetic breast implantation from
      June 1999 through October 2002. Nineteen percent of women who underwent initial
      implantation developed at least 1 adverse effect. Forty percent of the adverse
      effects occurred within 3 months of implantation; 79%, within 6 months. Capsular
      contracture grade II-IV was observed among 4.1% of women in the 2-year follow-up
      period. Overall, 97 (29%) of the 344 adverse effects among 55 (6%) of the 971
      women required surgical intervention. A higher incidence of adverse effects
      typically occurred after subsequent implantations. According to the DPB
      experience, we conclude that most short-term postoperative adverse effects
      following cosmetic implantation are clinically insignificant and do not require
      treatment and that short-term complications requiring adjuvant treatment are
      rare.

PMID- 14646642
TI  - Low incidence and prevalence of hepatitis C virus infection among sexually active
      non-intravenous drug-using adults, San Francisco, 1997-2000.
AB  - BACKGROUND: The rate of sexual transmission of hepatitis C virus (HCV) is
      debated. GOAL: The goal was to measure the risk of sexual transmission of
      hepatitis C virus (HCV) in a sexually active population. STUDY DESIGN: Sexual
      behaviors and HCV antibody status were measured in persons seeking repeat HIV
      testing in San Francisco from October 1997 through March 2000. RESULTS: Among 981
      repeat testers, the prevalence of HCV antibody was 2.5%. Among men who have sex
      with men who denied intravenous drug use (n=746), factors associated with HCV
      antibody positivity include age greater than 50 years (odds ratio [OR], 8.5; 95%
      confidence interval [CI], 2.6-27.7), HIV infection (OR, 5.7; 95% CI, 1.6-20.6),
      and being nonwhite (OR, 3.3; 95% CI, 1.1-10.0). HCV antibody positivity was not
      associated with sexual risk behaviors. In 576.6 person-years of observation, no
      new HCV seroconversions occurred (incidence=0 per 100 person-year; 95% CI, 0-.6),
      whereas 6 new herpes simplex virus-2 infections (2.8 per 100 person-years) and 10
      new HIV infections (1.8 per 100 person-years) occurred. CONCLUSION: The absence
      of new HCV infections in this sample supports the hypothesis that the risk of
      sexual transmission of HCV is low.

PMID- 14646644
TI  - Revision augmentation mastopexy: indications, operations, and outcomes.
AB  - In the absence of any published information on the indications, frequency, and
      outcomes of revision augmentation/mastopexy, an 8-year retrospective review was
      undertaken of all patients undergoing revision of a previous
      augmentation/mastopexy in the senior author's practice. The data collected
      included original implant type, location and mastopexy type, indication for
      revision, interval from original surgery, new implant type, location, and
      associated corrective surgical procedures. A simultaneous review was also
      performed of all primary augmentation/mastopexies done during the same period.
      Twenty patients underwent revision of 34 previously performed
      augmentation/mastopexies. Five patients underwent revisions of a prior revision.
      Fourteen were bilateral, while 6 were unilateral, for a total of 34 breasts.
      Forty patients underwent primary augmentation/mastopexy during the same period.
      Among the revisions, 10 implants were originally subglandular, while 24 were
      either partly or totally submuscular. Twelve of the previous mastopexies were
      periareolar, 2 were vertical, and 20 were of the inverted T-type. The indications
      for revision included capsular contracture in 11 of 20 (55%) patients, nipple
      ptosis in 11 of 20 (55%) patients, implant malposition in 7 of 20 (35%) patients,
      dissatisfaction with implant size in 6 of 20 (30%) patients, poor scar in 5 of 20
      (25%) patients, breast ptosis in 4 of 20 (20%) patients, nipple malposition in 2
      of 20 (10%) patients, and patient preference in 1 of 20 (5%) patients. Most
      patients had 2 or more indications for revision. The average duration to revision
      was 7 years. In 13 of 20 (65%) patients, no change in implant type was made. The
      remainder had exchanges to a different type. In 12 of 20 (60%) patients, no
      change in implant location was made, whereas 8 of 20 (40%) patients had a change
      to the subpectoral or dual plane position. In 18 of 20 (90%) patients, the
      revision included the same type of mastopexy, while in 2 of 20 (10%) patients,
      the type of mastopexy was changed. Corrective surgical procedures performed
      included repeat mastopexy, capsulectomy, change of implant type, change of
      implant location, change of implant size, capsulotomy, capsulorrhaphy, and scar
      revision. To date, all of the patients are satisfied with their appearance.
      Follow-up ranged from 2 months to 4 years. Revision augmentation mastopexy is not
      an uncommon procedure, occurring half as often as primary augmentation/mastopexy
      in our series. There were 8 common indications for revision, with capsular
      contracture and recurrent ptosis being the most common. Eight surgical
      procedures, in various combinations, were performed during revision, with repeat
      mastopexy being the most common.

PMID- 14646645
TI  - Areola-sparing mastectomy with immediate breast reconstruction.
AB  - Skin-sparing mastectomy with immediate breast reconstruction is a proved option
      for patients with early-stage breast cancer requiring mastectomy. Based on the
      authors' recent pathologic analysis of mastectomy specimens showing less than 1%
      malignant involvement of the areola, they have begun to perform areola-sparing
      mastectomies (ASMs) on a select group of patients. They report their results from
      an ongoing study of ASM at their institution. During a 20-month period, 17 ASMs
      with immediate reconstruction were performed on 12 patients. Mastectomy was
      performed for breast cancer prophylaxis (n = 10), ductal carcinoma in situ (n =
      4), and less than 2 cm of peripheral infiltrating carcinoma (n = 3). The most
      frequent incision performed was intraareola (n = 13). Thirteen patients were
      reconstructed with tissue expanders and 4 with pedicled transverse rectus
      abdominis musculocutaneous flaps. There was 1 postoperative complication, which
      consisted of a localized wound infection. Overall the authors found that ASM with
      immediate reconstruction provides excellent aesthetic results with infrequent
      complications.

PMID- 14646646
TI  - The effect of body mass index and wound irrigation on outcome after bilateral
      breast reduction.
AB  - Thirty patients undergoing bilateral breast reduction by inferior pedicle
      technique were entered into a prospective, randomized study to determine the
      effect of unilateral saline wound irrigation and body mass index (BMI) on
      outcome. Each patient was assessed at 1, 4, and 8 weeks after surgery for wound
      dehiscence, infection, fat necrosis, and breast comfort by means of a visual
      analog pain score. The mean patient age was 33 years; mean weight, 67.7 kg; mean
      BMI, 26.3; and mean weight of breast tissue excised per patient, 1270 g. In 60
      breasts there were 13 cases of minor wound breakdown, all of which had healed by
      8 weeks postoperatively. Wound irrigation had no significant effect on the rate
      of T-junction breakdown or on postoperative pain. BMI was associated
      significantly with wound breakdown (BMI > 26.3, 33% wound breakdown rate; BMI <
      26.3, 10% wound breakdown rate; P < 0.05, chi2 test). Patients with a high BMI
      are more likely to have delayed healing after breast reduction.

PMID- 14646647
TI  - Modification of the vertical rectus abdominis musculocutaneous (VRAM) flap for
      functional reconstruction of complex vulvoperineal defects.
AB  - Radical vulvoperineal ablations present challenging reconstructive dilemmas,
      especially when local metastatic spread requires distal vaginal and anal
      resection. Despite advances in vaginal salvage and sphincteroplasty, surface
      recontouring remains elusive because of the necessity to resurface a large,
      complex area that includes the mons, vulva, and fourchette. We describe a
      modification of the inferior-based vertical rectus abdominis musculocutaneous
      (VRAM) flap where the superior portion is split longitudinally to produce
      "tongue" flaps, which can resurface complex vulvoperineal wounds. By splitting
      the flap, one can resurface the vulva, provide an edge to reattach the vaginal
      cuff, and recreate the fourchette and line the anoderm after anoplasty. This
      musculocutaneous flap provides adequate contour and protection against radiation
      injury. Splitting of the flap is based on the vascular territory of the superior
      epigastric branches and their perforators and can be carried down to the level of
      their anastomosis, with the inferior system at the level of the umbilicus. The
      split VRAM flap has been used successfully in 3 patients with complex perineal
      wounds with excellent results and maintenance of vaginal patency.

PMID- 14646648
TI  - Deep inferior epigastric artery perforator flaps in head and neck reconstruction.

PMID- 14646649
TI  - Long-term results of replantation for complete ring avulsion amputations.
AB  - Ring avulsion injuries have long presented complex management problems. Despite
      microsurgical advances, it is difficult to achieve good functional results in
      complete degloving injuries or amputations, and their management remains somewhat
      controversial. Ten patients with class IV injuries according to Kay's
      classification were treated from 1986 to 2000. In this study the authors
      subdivided class IV injuries into those with amputation distal to the insertion
      of the flexor digitorum superficialis tendon (class IVd, 5 cases); those with
      amputation proximal to the insertion of the flexor digitorum superficialis tendon
      (class IVp, 3 cases); and complete degloving injuries leaving the tendons intact
      (class IVi, 2 cases). Replantation was done in class IVi and class IVd injuries,
      and 6 cases were revascularized successfully. In all these patients range of
      motion was complete at the metacarpal and proximal interphalangeal joints, but
      reestablishing sensibility was more difficult. Patients with class IVp injuries
      were treated by surgical amputation of the digit. Modifications of Kay's
      classification system based on anatomic injury is more predictive of functional
      outcome for completely amputated ring avulsion injuries. The authors conclude
      that complete ring avulsion amputations are salvageable, with acceptable
      functional results in select patients.

PMID- 14646651
TI  - Effect of steroids on edema, ecchymosis, and intraoperative bleeding in
      rhinoplasty.
AB  - A double-blind, randomized study was designed to determine the efficacy of
      dexamethasone in decreasing periorbital edema and ecchymosis after rhinoplasty.
      Sixty rhinoplasty patients undergoing hump resection and lateral osteotomy were
      included in the study and were divided into 6 groups: group 1 (n = 10), single
      dose of 8 mg intravenous (IV) dexamethasone 1 hour before the operation; group 2
      (n = 10), single dose of 8 mg IV dexamethasone at the beginning of the operation;
      group 3 (n = 10), 3 doses of 8 mg IV dexamethasone 1 hour before the operation,
      and 24 and 48 hours after the operation; group 4 (n = 10), 3 doses of 8 mg IV
      dexamethasone at the beginning of the operation, and 24 and 48 hour after the
      operation; group 5 (n = 10), 3 doses of 8 mg IV dexamethasone immediately after
      the operation, and 24 and 48 hours after the operation; group 6 (n = 10),
      control, no dexamethasone administration before or after the operation.
      Intraoperative blood loss was recorded for each patient. Patients were evaluated
      at 24 hours and days 2, 5, 7, and 10. For the postoperative evaluation of
      periorbital ecchymosis and edema, a scale of 0 to 4 points was used. There was no
      significant difference between groups in terms of bleeding (P > 0.05). In the
      groups using steroid before osteotomy, edema and ecchymosis were significantly
      lower during the first 2 days compared with the control group (P < 0.05). No
      significant difference was seen between groups 1 and 2. When patients were
      evaluated on day 5, edema and ecchymosis were significantly lower in groups 3 and
      4 (P < 0.05) compared with other groups, but there was no difference between
      them. Group 5 had a significantly higher level of edema and ecchymosis compared
      with groups 1 through 4 at 24 hours and at days 2, 5, and 7 (P > 0.05). There was
      no significant difference between groups on day 10. In conclusion, if the first
      dose is given before osteotomy, triple-dose steroid application is the best bet
      for decreasing postoperative edema and ecchymosis. None of the patients had any
      complications related to the use of dexamethasone.

PMID- 14646652
TI  - A minimalist approach to the care of the indwelling closed suction drain: a
      prospective analysis of local wound complications.
AB  - Despite their long-standing and prevalent use, closed suction drains lack a
      standardized postoperative care protocol. The authors present a prospective
      analysis of local wound problems associated with a minimalist approach to care of
      the drain exit site. A total of 73 patients undergoing a variety of procedures
      had 192 closed suction drains left in place on average over 10 days after
      surgery. Drain care consisted of daily showering with soap and water for the
      skin, no dressings, and stripping and emptying of the drain by the patient.
      Ninety-one percent of the patients followed the drain protocol and showered
      postoperatively without particular attention to the drains. There were 5 major
      complications of fluid collections leading to open wounds, 5 minor wound
      complications, and 2 wound complications unrelated to drain exit site care.
      Patient follow-up averaged 10 months. Overall, these data underscore the safety
      and efficacy associated with a simple approach to the management of closed
      suction drains.

PMID- 14646653
TI  - Medial and lateral malleolar perforator flaps for repair of defects around the
      ankle.
AB  - Reconstruction for defects around the ankle continues to be challenging. Repairs
      have been effected with the dorsalis pedis flap, the medial plantar flap, and
      with reverse-flow island flaps using the anterior and posterior tibial systems
      and the peroneal system. However, sacrifice of the major vessels of the lower leg
      and wide and long scars at the donor site are disadvantages of these flaps. To
      overcome these disadvantages, the authors developed island lateral and medial
      malleolar flaps with the perforators located close to the ankle. These flaps are
      easy to elevate, involve a short operating time, require no sacrifice of major
      vessels or muscles of the lower legs, and the use of these adipofascial flaps
      makes donor scars more acceptable. Malleolar perforator flaps are suitable for
      the repair of small ankle defects.

PMID- 14646654
TI  - Eyebrow transplantation.
AB  - The eyebrow has a powerful influence on the appearance of the orbital region.
      Because the person without eyebrows has an unnatural look, drawing everyone's
      attention, eyebrow restoration/reconstruction should be viewed as an esthetic
      surgery performed to improve the patient's appearance and self-esteem. Although
      hair-bearing pedicled flaps and free composite strip grafts have been the most
      widely used approaches in clinical practice formerly, follicular unit
      transplantation (FUT) has gained more and more importance nowadays in eyebrow
      restoration because of its more rewarding results. The process and results of FUT
      have been greatly improved thanks to advances in hair transplantation techniques,
      instrumentation, and practice. In this article, we discuss the restoration of 14
      eyebrows in 8 patients (5 males and 3 females) using FUT. The procedure and the
      results also are discussed here under in light of literature.

PMID- 14646655
TI  - Advantages of the presence of living dermal fibroblasts within restylane for soft
      tissue augmentation.
AB  - For the elimination of facial wrinkles and skin contour defects, injectable
      filler substances composed of commercially prepared nonanimal stabilized
      hyaluronic acid (Restylane) are now widely used. Although this method of
      suspension has been shown to be relatively safe and convenient, varying degrees
      of resorption have required repeated percutaneous injections. This study was
      undertaken to evaluate the feasibility of Restylane, which is a modified
      hyaluronic acid, combined with cultured human dermal fibroblasts, to enhance the
      longevity of injected implants. The histologic changes of the injected implants
      were also evaluated. For the test group, fibroblasts from the dermis of healthy
      adults were isolated and cultivated. The cultured fibroblasts were measured with
      a hemocytometer. Five x 105 fibroblasts suspended in 200 microl of Dulbecco
      phosphate-buffered saline (DPBS) were then dispersed in 200 microl of Restylane
      to form a 400-microl human fibroblast-Restylane mix. For the control group, 200
      microl of DPBS without fibroblasts were mixed with 200 microl of Restylane. These
      implants were subcutaneously injected into the back of an athymic nude mouse at 6
      sites, the 3 left sites composing the control group and the 3 right sites
      composing the test group. Twelve nude mice were injected for a total of 36
      injections per group. The nodular swellings that resulted from the injections
      were excised to include skin beyond the swelling points down to the panniculus
      carnosus layer using 5-mm punches, and the weights were measured at 1, 2, 4, 8,
      12, and 16 weeks after the injections. Histologic comparisons were also performed
      to confirm the presence of human collagen in the fibroblast-mixed Restylane group
      using immunohistochemical study with antihuman collagen type I polyclonal
      antibody. The mean weight of the control group nodules decreased throughout the
      examination period. The mean weight at the 16th week was 60% of the weight at the
      first week. On the other hand, the mean weight of the test-group nodules
      decreased only over the first 2 weeks. Beyond 2 weeks, there was no further
      significant weight change. The mean weight at the 16th week was 91% of the weight
      measured at the first week. Histologic examinations of the control group
      exhibited negative immunohistochemical staining for human collagen at each
      examination period. The test group exhibited positive staining after 2 weeks,
      indicating the presence of human collagen. These results indicate that Restylane
      mixed with cultured human dermal fibroblasts may be successfully injected as
      living grafts for long-term retention of implants.

PMID- 14646656
TI  - Human skin allograft used to treat open wounds after club foot release.
AB  - The inversion deformity of club foot is characterized by shortened ligaments and
      tendons on the medial side of the foot. The condition, when refractory to
      castings, is treated easily by operative intervention with neutralization of the
      foot and ankle. Closure of the resulting incision creates tension on the skin
      that is well tolerated in most children. Correction of severe deformities leaves
      incisions that will not close primarily, leaving tendons and neurovascular
      structures exposed on the posteromedial aspect of the foot. Free tissue transfer
      or spontaneous secondary closure are 2 options that have drawbacks. Application
      of human skin allograft affords protection to underlying tissue while allowing
      granulation tissue formation and wound contraction. Subsequent skin autograft and
      secondary skin contraction and epithelialization provide satisfactory wound
      closure with normal foot contour and preservation of ankle correction. Complete
      healing is achieved by the time cast immobilization is discontinued 6 weeks after
      surgery.

PMID- 14646658
TI  - A new experimental flap model: free muscle perforator flap.
AB  - A large number of perforator flap types have been described in experimental and
      clinical studies. Perforator flaps have been used both as pedicled and free flaps
      in clinical practice, but only in a pedicled form in animal studies. According to
      the authors' literature review, a free perforator flap in an animal model has not
      yet been developed. The purpose of this study was to describe a new free
      perforator flap model in the rat. A total of 15 Wistar rats weighing 200 to 250 g
      were used in this experiment. In 5 rats, the vascular anatomy of the popliteal
      vessels and their relation with adjacent structures were determined by anatomic
      dissection. In the remaining 10 rats, a posterior thigh perforator-based flap was
      created based on the distal popliteal vascular pedicle. In 5 rats the flap was
      transferred to the groin region as a free flap. In the remaining 5 rats the flap
      was transferred to the groin region, but in this group anastomosis was not
      performed between the vascular structures of the flap and the recipient femoral
      vessels. The latter group was designated as the control group. Direct observation
      and microangiographic techniques were used to assess the viability of the flap.
      Results showed that the cutaneous islands of all the free flaps survived
      completely, whereas in the control group all the flaps under-went total necrosis.
      The authors conclude that the free posterior thigh perforator flap is a reliable
      and true perforator flap model for future physiologic, biologic, and
      pharmacologic studies. It offers the following advantages: 1) Arising from the
      biceps femoris muscle, the musculocutaneous perforator of the flap has a
      consistent vascular pedicle, 2) it is the first free perforator flap for the rat,
      3) it is harvested from a small-animal species, and 4) it can be used without the
      need for an isogeneic rat.

PMID- 14646657
TI  - Acellularization of human placenta with preservation of the basement membrane: a
      potential matrix for tissue engineering.
AB  - Basement membrane directs cell migration, cell adherence, and tissue organization
      in vivo. These qualities would be advantageous in tissue engineering, during
      which repopulation of scaffolds by functional cells is a common problem. The
      purpose of this study was to expose human term placenta to a chemical
      acellularization protocol using the isolated cotyledon perfusion technique to
      develop an acellular scaffold rich in extracellular matrix components for tissue
      engineering applications. The processed blocks of tissue demonstrated no cellular
      material on histologic examination. Periodic acid-Schiff staining, type IV
      collagen labeling, and transmission electron microscopy demonstrated preservation
      of the extracellular matrix and basement membrane. Maintenance of the
      extracellular matrix architecture was seen on scanning electron microscopy.
      Placenta-derived acellular matrix is a potential volume scaffold for tissue
      engineering. It is rich in extracellular matrix, has a complex architecture of
      vascular channels, and has unique donor opportunities.

PMID- 14646659
TI  - Two case reports of pollicization of a previously syndactylized index finger for
      congenitally absent thumb.
AB  - Two patients with absent thumbs and complicated syndactyly were successfully
      treated by pollicization of the index finger. Prior surgical release of the index
      finger syndactyly and then pollicization of that digit carries with it an
      increased risk of neurovascular compromise, adverse placement of surgical scars,
      and a stiff or unstable thumb. With caution, very satisfying reconstructive
      results can nonetheless be attained.

PMID- 14646661
TI  - Sequential use of a true perforator flap and its corresponding muscle flap.
AB  - A true perforator flap completely spares the underlying muscle that was
      previously required as essentially a passive carrier of that musculocutaneous
      unit. Thus, a perforator flap and its related muscle can now be simultaneously
      transferred as independent but conjoint flaps based on the same source pedicle,
      or sometimes also in a metachronous fashion if the requisite source vessels
      remain intact. The latter principle proved feasible after failure of 2 medial
      sural perforator flaps that were subsequently successfully replaced by a
      conventional medial gastrocnemius muscle flap. At least theoretically, depending
      on the extent of intramuscular dissection, another advantage that can be applied
      to all perforator flaps is that the muscle can be held in reserve for sequential
      use as necessary.

PMID- 14646663
TI  - The gracilis (medial circumflex femoral) perforator flap: a medial groin free
      flap?
AB  - The superior medial thigh skin territory has previously been successfully
      transferred as a free flap as part of a gracilis musculocutaneous flap. However,
      muscle bulk can be avoided and its function preserved by instead retaining only
      the musculocutaneous perforators arising from the gracilis pedicle like in a true
      perforator flap. A clinical example of this new perforator flap is described as
      the gracilis (medial circumflex femoral) perforator flap. This could become an
      ideal skin flap because no muscle is included, a well-defined segment of skin can
      be reliably harvested, closure of the donor site leaves a scar in the groin that
      can be readily concealed, and its dominant vascular pedicle is consistent in
      location and already familiar to most reconstructive surgeons.

PMID- 14646664
TI  - Long-term follow-up and unusual findings after microvascular transfer of hair
      bearing skin for pubic hair restoration.
AB  - Alopecia in the pubic area can be restored successfully with hair transplantation
      using minigrafts and micrografts or with free tissue transfer of a hair bearing
      flap. In this report the authors present the successful transfer of hair bearing
      tissue from the temporoparietal scalp for the correction of a congenital form of
      alopecia of the pubic region. In addition, they present long term results of this
      transfer. Auxiliary procedures such as tissue expansion before or after
      transferring the flap, hair epilation and minigraft and micrograft
      transplantation could help to achieve a more natural result. Tissue expansion of
      the donor site could also be performed to enhance the outcome of the procedure.
      Of note is the rapid rate of hair growth in the transplanted tissue. This type of
      reconstruction using a hair bearing temporoparietal flap for restoration of hair
      to the pubic region is a useful method that can yield good results.

PMID- 14646665
TI  - Muscle perforator flaps: the name game.
AB  - The creation of a consistent nomenclature for muscle perforator flaps is
      essential not only to eliminate confusion in the literature, but also to
      facilitate their surgical application. Universal acceptance demands that the
      chosen system be as simple as possible, yet remain comprehensive and flexible
      enough to anticipate future adaptations. Flaps named by anatomical region alone
      can be ambiguous due to the frequent variations in perforator origin and
      sometimes multiple or overlapping "mother" vessels, which unfortunately is an
      inherent characteristic of muscle perforator flaps. One sensible solution is an
      appellation that includes both the involved muscle and its source vessel, in any
      order, eg. "source vessel(MUSCLE)" or "muscle(SOURCE VESSEL)" perforator flap.
      Such a combination immediately readily identifies the precise anatomical location
      of the flap, as well as stating exactly which vascular pedicle must be dissected.

PMID- 14646666
TI  - Inexpensive self-retaining retractor for minor surgical procedures.
AB  - The need for adequate surgical exposure frequently leads to the use of hand-held
      retractors, tying up operating room personnel and depriving the assistant a
      direct view of the procedure. Self-retaining retractors are a great help because
      they assist in obtaining and maintaining the exposure needed for surgery.
      Traditional self-retaining retractors often have sharp tips that are capable of
      damaging tissue. Our self-retaining ring retractor uses material already present
      in the sterile field and can be constructed in less than 3 minutes. It is
      efficient, easy to use, and exerts a known and finite amount of force, thereby
      avoiding tissue damage.

PMID- 14646667
TI  - Correction of inverted nipple: an alternative method using two triangular areolar
      dermal flaps.
AB  - Inverted nipple, which is defined as a nipple located on a plane lower than the
      areola, presents both functional and cosmetic problems. It is a source of
      repeated irritation and inflammation, and interferes with nursing. In addition,
      its abnormal appearance may cause psychological distress. Inverted nipples are
      congenital or acquired, and are classified as the umbilicated and invaginated
      types or divided into 3 groups (grades 1, 2, and 3). With consideration of its
      underlying pathophysiologic components and severity, various surgical procedures
      have been proposed. For correcting the inverted nipple, the authors introduce an
      alternative, simple method using 2 triangular areolar dermal flaps. Compared with
      other methods using triangular areolar dermal flaps, each triangle is
      approximately 1 mm shorter than the diameter of the nipple, and the
      deepithelialized areolar dermal flaps are lodged at the slit in the bundle of the
      lactiferous ducts in the grade 2 inverted nipple. From August 2000 to December
      2001, 11 patients (16 nipples) were treated. Five patients had bilateral inverted
      nipples. Patient age at operation ranged from 18 to 31 years (mean age, 27
      years). All nipples were congenital and they had no previous operation. Thirteen
      nipples were grade 2 and 3 were grade 3 according to the classification of
      inverted nipple by Han and Hong. The mean follow-up period was 8.7 months (range,
      3-12 months). Follow-up examinations revealed no evidence of recurrence of
      inversion. There was no complication associated with surgery, such as infection,
      hematoma, permanent sensory disturbance, or nipple necrosis. The resulting scars
      were minimal. All patients were satisfied with their results. The authors
      conclude that their procedure is reliable, preserves the lactiferous ducts in
      grade 2 inverted nipple, requires no special postoperative care, and leaves
      minimal scars and no recurrence of inversion. This technique can be applied to
      any type of inverted nipple as a primary surgical procedure.

PMID- 14646668
TI  - Double opposing V-Y hinge flap.
AB  - A relatively large earlobe hole was closed with triangular flaps on both sides
      using a V-Y plasty. The design and elevation of this flap are simple and easy.
      This flap can close relatively large earlobe holes, preventing earlobe deformity.

PMID- 14646669
TI  - The mother of all myths.

PMID- 14646672
TI  - New-onset conduction defects and their relationship with in-hospital major
      cardiac events in unstable angina pectoris.
AB  - BACKGROUND: The aim of this prospective cohort study was to describe the
      incidence and the risk factors for the development of intraventricular conduction
      defects and the relationship of these defects with in-hospital major cardiac
      events (MACE) in unstable angina pectoris. METHODS: Two-hundred-and-seventy
      consecutive patients presenting with Braunwald class IIIB angina without a
      conduction defect at admission were included in the study and followed up during
      the in-hospital period. RESULTS: Fifty-one patients who developed non-ST
      elevation myocardial infarction during the first day were excluded from the
      study. Of the remaining 219 patients, 40 (18%) had a new permanent conduction
      defect (group 1) and 179 (82%) did not have a conduction defect (group 2) during
      the in-hospital period. The patients in group 1 were significantly older (mean
      age of 63.5 +/- 11 years compared with 59 +/- 10 years, P = 0.01) and a history
      of previous coronary artery bypass grafting (CABG) was more frequent in this
      group (12.5% compared with 1.6%, P = 0.004). By logistic regression analysis, age
      (P = 0.01, odds ratio (OR) = 1.473, 95% confidence interval (CI) = 1.108-2.612)
      and previous CABG (P = 0.005, OR = 3.995, 95% CI = 1.811-7.383) were also found
      to be risk factors for the development of a conduction defect. In-hospital total
      MACE, death and heart failure were more frequently observed in group 1 (P =
      0.005, P = 0.02, P = 0.001, respectively). The incidences of recurrent refractory
      angina, acute myocardial infarction and urgent revascularization were not
      different between the groups. ST-segment depression at admission (P = 0.009, OR =
      1.654, 95% CI = 1.228-2.675) and a new-onset conduction defect (P = 0.02, OR =
      1.625, 95% CI = 1.244-2.754) were found to be predictors of the development of in
      hospital MACE. CONCLUSIONS: In unstable angina pectoris, patients with a new
      onset conduction defect are relatively older and have more frequently undergone
      previous CABG. Because in-hospital MACE, death and heart failure are more common
      in patients with a new conduction defect, they should be considered as high risk
      and treated more aggressively.

PMID- 14646673
TI  - A QRS score versus ST-segment changes during exercise testing: which is the most
      reliable ischaemic marker after myocardial revascularisation?
AB  - BACKGROUND: The diagnostic ability of exercise testing based on ST-segment
      changes is low for the detection of restenosis after percutaneous transluminal
      coronary angioplasty (PTCA) or ischaemia after bypass surgery (CABG). The aim of
      this study was to improve the diagnostic accuracy of exercise testing in patients
      with a history of PTCA or CABG, with the implementation of a QRS score. METHODS:
      We studied 128 post-PTCA patients (aged 49 +/- 8 years) and 104 post-CABG
      patients (aged 54 +/- 8 years), who had either positive exercise tests with or
      without angina, or negative exercise tests with continuing angina-like symptoms,
      and underwent cardiac catheterisation. RESULTS: The univariate risk ratio of
      exercise-induced ST-segment deviation to detect restenosis was 3.05 (p = 0.005)
      and 0.83 (p = 0.690) in group A and group B patients, respectively. The
      univariate risk ratios of abnormal QRS score values to detect restenosis were
      32.1 (p < 0.001) and 18.8 (p < 0.001) for group A and group B patients,
      respectively. The univariate risk ratios of the combination of exercise-induced
      ST-segment changes and of abnormal QRS score values to detect restenosis was 9.43
      (p < 0.001) and 3.77 (p < 0.044) for group A and group B patients, respectively.
      The value of the area under the ROC curves is higher for the QRS score in group A
      patients, group B patients and for the whole study population. CONCLUSIONS: QRS
      score values significantly improve the diagnostic ability of ST-segment change
      based exercise testing, for the assessment of restenosis after PTCA or ischaemia
      after CABG.

PMID- 14646674
TI  - Effect of leisure time physical activity on blood lipid levels: the ATTICA study.
AB  - OBJECTIVE: We aimed to evaluate the effect of leisure time physical activity on
      blood lipid levels, in a random sample of cardiovascular disease-free individuals
      from the Attica basin. DESIGN AND METHODS: The ATTICA study is a population-based
      cohort, which during 2001-2002 randomly enrolled 2772 men (n = 1376, 45 +/- 12
      years old) and women (n = 1396, 45 +/- 13 years old). Physical activity status
      was evaluated through intensity (kcal/min expended per day), frequency (per week)
      and duration (min). Multivariate data analysis evaluated the association of blood
      lipids with physical activity levels. RESULTS: 578 (42%) men and 584 (40%) women
      were physically active. Compared to sedentary women, physically active women had
      lower levels of total cholesterol (P < 0.05), low-density lipoprotein (LDL) (P <
      0.05), oxidized LDL-cholesterol (P < 0.05), triglycerides (P < 0.05) and
      apolipoprotein B (P < 0.05) and higher levels of high-density lipoprotein (HDL)
      cholesterol (P < 0.05) and apolipoprotein A1 (P < 0.05). Similar associations
      were observed in men, but they did not reach statistical significance. However,
      after adjustments for age, smoking habits, body mass index and dietary intake
      were made, the effect of physical activity on blood lipids remained statistically
      significant only for HDL-cholesterol (P < 0.05) and apolipoprotein A1 (P < 0.05)
      levels in women. Moreover, physical activity was associated with lower total
      cholesterol levels both in nonsmoker men (-7%, P = 0.032) and nonsmoker women (
      2%, P = 0.064) and lower triglyceride levels in nonsmoker men (-15%, P = 0.086)
      and nonsmoker women (-9%, P = 0.036). CONCLUSIONS: Although almost all blood
      lipids were inversely associated with physical activity status, only HDL
      cholesterol and apolipoprotein A1 concentrations were significantly affected by
      exercise in women.

PMID- 14646675
TI  - Left ventricular hypertrophy and endothelial functions in patients with essential
      hypertension.
AB  - OBJECTIVE: In this study, we used a non-invasive method in patients with
      essential hypertension and without any overt clinical evidence of atherosclerosis
      to investigate the role of left ventricular hypertrophy (LVH) in endothelial
      functions. METHODS: We assessed endothelial function in 32 hypertensive patients
      with LVH (group 1), 28 hypertensive patients without LVH (group 2) and 29
      normotensive subjects (control group). Flow-mediated (endothelium-dependent) and
      nitrate induced (endothelium-independent) dilatation of the brachial artery was
      evaluated in all groups. RESULTS: Flow-mediated dilatation was considerably
      higher in the control group than in group 1 and 2 (13.98 +/- 2.92%, 4.67 +/-
      1.09% and 7.02 +/- 1.79% respectively, p < 0.001). In addition, endothelium
      dependent dilatation was significantly lower in group 1 than in group 2 (p <
      0.001), whereas nitrate induced changes were similar in all groups. CONCLUSION:
      Vascular endothelial functions are impaired in hypertensive patients. There may
      be heterogeneity of endothelial dysfunction among patients with hypertension.
      Presence of LVH has an additional negative effect on endothelial function in
      hypertensive patients.

PMID- 14646676
TI  - Addition of cytochalasin D to a biocompatible oil stent coating inhibits intimal
      hyperplasia in a porcine coronary model.
AB  - BACKGROUND: Polymer-based, drug-eluting stents, are currently under extensive
      investigation in the conquest against in-stent restenosis. Concern remains,
      however, about potential long-term lack of biocompatibility of the polymers used
      in these studies. Therefore, this study aimed to evaluate in porcine coronary
      arteries (1) the in vivo biocompatibility of a new natural, eicosapentaenoic acid
      oil stent-coating and (2) the efficacy of this coating in preventing in-stent
      restenosis when cytochalasin D--an inhibitor of actin filament formation, that
      interferes with cell proliferation and migration--was added. METHODS AND RESULTS:
      To assess in vivo biocompatibility of the oil coating, 15 bare and 15 oil-coated
      stents were randomly deployed in coronary arteries of 15 pigs. No difference in
      tissue response, regarding inflammation or proliferation, was seen between both
      groups at five days or at four weeks follow-up. To evaluate the efficacy of the
      coating in preventing in-stent restenosis by adding a potential anti-restenotic
      drug, stents were dip-coated in 20 mg cytochalasin D/ml oil solution, resulting
      in 93 +/- 18 microg cytochalasin D/stent load (n = 3). In vitro drug release
      studies showed sustained release up to four weeks. Next, 11 oil-coated and 11
      cytochalasin D-loaded stents were randomly implanted in coronary arteries of 11
      pigs. At four weeks, a 39% decrease in neointimal hyperplasia (p < 0.05, ANCOVA,
      with injury as covariate) was found in cytochalasin D-loaded stents compared to
      oil-coated stents. CONCLUSIONS: This new natural oil stent-coating shows
      excellent biocompatibility to vascular tissue. Local cytochalasin D delivery from
      this stent-platform significantly inhibits neointimal hyperplasia in a porcine
      coronary model.

PMID- 14646677
TI  - How are glaucoma patients identified?
AB  - PURPOSE: To determine the events that lead to the diagnosis of glaucoma. PATIENTS
      AND METHODS: This prospective study administered a questionnaire to consecutive
      patients in a university glaucoma service with questions about the visit at which
      their glaucoma was diagnosed. RESULTS: Among 308 patients (85% of those eligible)
      with glaucoma and those suspected of having glaucoma, more than half were
      diagnosed at a routine examination with no ocular symptom. One hundred fourteen
      of 202 (56%) of those patients were diagnosed with open angle glaucoma (OAG).
      Symptoms present at the diagnostic visit were infrequently related to glaucoma.
      Sixty-one percent of OAG patients (124 of 202) recalled elevated intraocular
      pressure (IOP) as the sole reason for their initial diagnosis; an additional 12%
      (24 of 202) recalled a combination of IOP with either disc or visual field
      findings. Only 18% (36 of 202) recalled being diagnosed due to disc or visual
      field damage alone. CONCLUSION: The detection of glaucoma is strongly associated
      with IOP measurement. Glaucoma is most frequently diagnosed at routine visits to
      eye care specialists at which patients either have no symptoms or have symptoms
      unrelated to glaucoma. Questionnaire information on large numbers of persons in
      the health care system may add to our knowledge of practice patterns.

PMID- 14646678
TI  - Cost of glaucoma in Canada: analyses based on visual field and physician's
      assessment.
AB  - PURPOSE: A longitudinal, retrospective study investigated the cost of primary
      open angle glaucoma (POAG). METHODS: Patient files from two tertiary care
      glaucoma practices were reviewed. Patients diagnosed with POAG and >/=2.5 years
      of follow-up data were included. Data collected included visual field mean
      deviation, physician's assessment, and resource utilization (physician visits,
      procedures, and medications). Costs, reported in 2001 Canadian dollars, were
      compared between groups, based on initial visual field mean deviation, including
      mild (<5 dB), moderate (5 to <12 dB), and severe (>/=12 dB), and based on
      physician's assessment, including controlled, uncontrolled, or patients initially
      uncontrolled for 12 months who become controlled. RESULTS: Of 411 patient charts
      extracted, 265 were included; 35 were excluded for ocular comorbidities and 111
      patients with insufficient follow-up. Mean (standard deviation) yearly costs
      overall (N = 265) and for mild (n = 90), moderate (n = 91), and severe (n = 84)
      groups were $508 ($278), $408 ($266), $512 ($288), and $609 ($243), respectively.
      Differences between mean yearly costs were statistically significant for all
      three groups (P < 0.05). Costs for controlled (n = 110), uncontrolled (n = 76),
      and uncontrolled then controlled group (n = 79) were $423 ($243), $594 ($314),
      and $542 ($256), respectively. The controlled group cost was significantly lower
      than both of the other groups (P < 0.05). DISCUSSION AND CONCLUSIONS: The cost of
      treating POAG increases with visual field mean deviation severity and
      uncontrolled disease. Many patients diagnosed with glaucoma had already
      progressed to later stages in the disease process. Early disease detection may
      provide a substantial cost savings to the health care system.

PMID- 14646679
TI  - Pooled-data analysis of three randomized, double-masked, six-month studies
      comparing intraocular pressure-reducing effects of latanoprost and timolol in
      patients with ocular hypertension.
AB  - PURPOSE: To assess retrospectively the intraocular pressure (IOP)-reducing effect
      of latanoprost compared with timolol in the subset of patients with ocular
      hypertension (OH). METHODS: Three randomized, double-masked, multicenter,
      parallel group, 6-month studies conducted in the United States, United Kingdom,
      and Scandinavia compared the efficacy and safety of latanoprost and timolol. The
      present study represents an analysis of the pooled data for the subset of OH
      patients. Intent-to-treat analyses were based on all randomized OH patients.
      RESULTS: Of the 441 patients with OH, 247 were treated with latanoprost and 194
      were treated with timolol. Baseline mean diurnal IOP levels were 24.4 +/- 0.2 mm
      Hg (mean +/- standard error of the mean) in the latanoprost group and 24.2 +/-
      0.2 mm Hg in the timolol group. Overall, latanoprost lowered mean diurnal IOP by
      1.1 +/- 0.2 mm Hg (95% CI: 1.6 to 0.7 mm Hg, P < 0.001) more than timolol. The
      difference in IOP-lowering ability between the two drugs was not shown to be
      related to patient sex, age, race, presence or absence of previous treatment of
      OH, time elapsed since ocular diagnosis, or family history of glaucoma/OH.
      Percentage reductions from baseline in diurnal IOP levels of at least 20% were
      achieved by 83% of patients treated with latanoprost versus 62% of those
      receiving timolol. CONCLUSION: Latanoprost provides superior IOP reduction
      compared with timolol in patients with OH.

PMID- 14646680
TI  - Rate of response to latanoprost or timolol in patients with ocular hypertension
      or glaucoma.
AB  - PURPOSE: This study determined the rate of response to latanoprost compared with
      timolol in patients with glaucoma or ocular hypertension, whether some patients
      convert from non-responders to responders after more prolonged therapy, and
      whether this conversion represents a delayed response or random fluctuation.
      METHODS: In a previously described, multicenter, randomized, double-masked,
      parallel group study, patients received either 0.005% latanoprost once daily (n =
      128) or 0.5% timolol twice daily (n = 140) for 6 months. Intraocular pressure
      (IOP) was assessed at baseline and at 0.5, 1.5, 3, 4.5, and 6 months of treatment
      at 8 am on all visits, and also at noon and 4 pm at baseline and 6 months. Rate
      of response based on diurnal measurement at 6 months compared with baseline was
      assessed using several criteria for response. Eyes with an IOP reduction of less
      than 15% compared with baseline at 8 am arbitrarily were classified as non
      responders at each of the 5 visits during treatment. Consistency of non-responder
      classifications for individual eyes was assessed. RESULTS: Mean IOP reduction was
      greater (P < 0.001) in latanoprost-versus timolol-treated patients throughout the
      course of therapy. A greater rate of response occurred in patients treated with
      latanoprost, and differences in response rates between the 2 drugs increased as
      the definitions of response became more stringent. A greater percentage of non
      responders at any single visit were classified as responders at all other visits
      with latanoprost in comparison with timolol. CONCLUSIONS: Latanoprost produces a
      greater rate of response compared with timolol. A higher percentage of non
      responders to latanoprost compared with timolol on any individual visit are
      responders on all other visits. Likewise, a higher proportion of patients who do
      not initially respond will become responders with continued treatment with
      latanoprost compared with timolol.

PMID- 14646681
TI  - Glaucomatous optic disc hemorrhages on confocal scanning laser tomographic
      images.
AB  - PURPOSE: To evaluate the detectability of glaucomatous optic disc hemorrhages by
      confocal scanning laser tomography. METHODS: The study included 73 eyes of 63
      patients, who consecutively showed optic disc hemorrhages on 15 degrees color
      optic disc photographs taken at baseline or during follow-up examinations and for
      whom confocal scanning laser tomographic images were additionally available. Of
      the total number of 92 observed hemorrhages, 51 hemorrhages extended into the
      parapapillary region and 41 hemorrhages were restricted to the intrapapillary
      region. The scanning laser tomographic images were searched for the disc
      hemorrhages already seen on the conventional disc photographs. RESULTS: Using the
      reflectivity images, 29 (32%) hemorrhages were detected on the scanning laser
      tomographs. None of the hemorrhages restricted to the intrapapillary region could
      be seen on the scanning laser tomographs. By evaluating each of the 32 single
      images of the scanning laser tomographic image series, 44 (48%) of the
      hemorrhages were identified on at least one single image. The detectability of
      disc hemorrhages on the scanning laser tomographs depended significantly on their
      extension into the parapapillary region or their intrapapillary location.
      Detectability of disc bleedings was statistically independent of the disc
      quadrant where the hemorrhage was located, width of the bleeding, size of the
      optic disc, neuroretinal rim, parapapillary atrophy, and type of glaucoma.
      CONCLUSIONS: Confocal scanning laser tomography is not very suitable for
      detection or documentation of optic disc hemorrhages in patients with glaucoma.

PMID- 14646682
TI  - Corneal punctate staining with latanoprost, bimatoprost, and travoprost in
      healthy subjects.
AB  - PURPOSE: To evaluate short-term conjunctival and corneal punctate staining with
      latanoprost, bimatoprost, and travoprost in healthy individuals. MATERIALS AND
      METHODS: A single centered, active-controlled, three-period crossover comparison
      that evaluated conjunctival and corneal punctate staining, by grade and
      individual stains, in healthy subjects after dosing for five days in one eye with
      latanoprost, bimatoprost, or travoprost. Staining was evaluated at 24-hour trough
      (Hour 0) and at Hour 1 after dosing. RESULTS: Twenty-eight subjects completed
      this study. This study found that there was no significant difference by ANOVA
      for the number of individual corneal punctate stains either at trough
      (latanoprost 22.6 +/- 25.4, bimatoprost 16.8 +/- 25.6, and travoprost 21.1 +/-
      26.0 mm Hg) (P = 0.33) or at 1 hour after dosing (latanoprost 23.8 +/- 26.3
      bimatoprost 18.2 +/- 25.2, and travoprost 26.1 +/- 26.1 mm Hg) (P = 0.75) among
      treatment groups. No significant differences existed among treatment groups in
      the study eye compared with the non-study eye or to the study eye at Hour 0 or
      Hour 1 or to the period initiation or baseline visits (P > 0.05). Several
      significantly different comparisons, inconsistent in nature, were observed for
      the nasal and temporal conjunctival staining between the treatment groups. There
      were no differences in unsolicited or solicited adverse events between groups.
      CONCLUSION: This study suggests that, in healthy subjects after short-term
      treatment, latanoprost, bimatoprost, and travoprost demonstrate generally similar
      ocular surface epithelial staining characteristics.

PMID- 14646683
TI  - Ocular factors relevant to anti-glaucomatous eyedrop-related
      keratoepitheliopathy.
AB  - PURPOSE: To evaluate the ocular factors contributing to keratoepitheliopathy in
      glaucoma patients treated with or without anti-glaucomatous eyedrops, and the
      influences of each anti-glaucomatous eyedrop to keratoepitheliopathy. METHODS:
      The presence and severity of keratoepitheliopathy was investigated in 193 eyes of
      110 glaucoma patients. The ocular factors examined were the status of the lipid
      layer of the tear fluid as assessed by a specular reflection video-recording
      system, tear volume assessed by Schirmer's test, and tear film stability assessed
      by tear break-up time. The influences of combined anti-glaucomatous eyedrops and
      each anti-glaucomatous eyedrops to keratoepitheliopathy were investigated.
      RESULTS: The overall occurrence of superficial punctate keratitis was 29.0%.
      Superficial punctate keratitis was more frequently observed in patients who used
      more than two anti-glaucomatous eyedrops (35.9%) than in those who used without
      (19.7%) and one (30.9%). Results of Schirmer's test and break-up time were worse
      in patients who used combined medication. The occurrence of superficial punctate
      keratitis in patients who used timolol (46.2%) was significantly more frequent
      than in those who used carteolol (4.2%). Severity of superficial punctate
      keratitis and break-up time in patients who used timolol were significantly worse
      than in those who used carteolol. There were no differences of
      keratoepitheliopathy and ocular factors between patients who used latanoprost and
      unoprostone. CONCLUSION: The usage of multiple anti-glaucomatous eyedrops induces
      keratoepitheliopathy by reducing the tear volume and the tear film stability.
      Carteolol may be used more safely for corneal epithelium.

PMID- 14646684
TI  - Comparison of the short-term effects on the human corneal surface of topical
      timolol maleate with and without benzalkonium chloride.
AB  - PURPOSE: To compare the short-term effects of timolol maleate with and without
      preservative (0.005% benzalkonium chloride) on pre-corneal tear film stability
      and corneal epithelial barrier function. SUBJECTS AND METHODS: The study
      population consisted of 20 healthy volunteers. To obtain baseline values, 7 days
      before the experiment the non-invasive breakup time of the pre-corneal tear film
      was measured using a tear specular microscope; corneal fluorescein uptake was
      measured with a fluorophotometer. Unpreserved or preserved 0.5% timolol was
      applied to one eye; the contralateral eye was exposed to the other drug. At 30
      minutes after instillation, the pre-study tests were repeated. RESULTS: Preserved
      timolol did, while unpreserved timolol did not, significantly reduce the non
      invasive breakup time from the baseline values (baseline and post-exposure values
      11.4 and 6.8 seconds, respectively, P = 0.008 for preserved timolol, and 11.7 vs.
      11.0 seconds, P = 0.55 for unpreserved timolol). Corneal fluorescein uptake, on
      the other hand, was significantly increased upon exposure to either preserved or
      unpreserved timolol (baseline and post-exposure values 37.5 and 82.0 ng/ml, P <
      0.001 for preserved timolol, and 35.4 vs. 57.6 ng/ml, P < 0.001 for unpreserved
      timolol). Preserved timolol exerted the greater effect (P = 0.028). CONCLUSIONS:
      Exposure to preserved timolol resulted in significant instability in the pre
      corneal tear film. Moreover, it disrupted the corneal epithelial barrier function
      to a greater degree than unpreserved timolol. The elimination of preservatives
      may be desirable in efforts to protect the integrity of the corneal surface and
      its interaction with the tear film.

PMID- 14646685
TI  - Dense pigmentation of the posterior lens capsule associated with the pigment
      dispersion syndrome.
AB  - PURPOSE: To report an unusual case of pigment dispersion syndrome associated with
      unilateral dense pigmentation of the posterior lens capsule. METHODS: Case
      report. RESULTS: A 59-year-old male with bilateral pigment dispersion syndrome
      presented with progressive decrease in visual acuity in the left eye over the
      past 10 to 20 years. Clinical examination revealed the typical findings of
      pigment dispersion syndrome including the presence of bilateral Krunkenberg
      spindles, iris transillumination defects, and heavy trabecular meshwork
      pigmentation. Of note, there was remarkably dense pigmentation of the posterior
      lens capsule in the eye with decreased visual acuity. CONCLUSION: Pigmentation of
      the posterior lens capsule may be a rare finding associated with pigment
      dispersion syndrome. Such a finding suggests that there may be aqueous flow into
      the retrolental space in some patients with this condition. The optimal treatment
      of this unusual condition remains undetermined.

PMID- 14646686
TI  - Thyroid eye disease and glaucoma.

PMID- 14646687
TI  - Re: laser peripheral iridoplasty as initial treatment of acute attack of primary
      angle-closure: a long-term follow-up study.

PMID- 14646688
TI  - Homocysteine in primary and secondary open-angle glaucoma.

PMID- 14646689
TI  - Pharmacogenetics of hypertension treatment: a structured review.
AB  - The extent of blood pressure lowering by anti-hypertensive agents is difficult to
      predict for individual patients, even when evaluated in the context of
      biochemical or demographic information. Genetic predictors (mainly single
      nucleotide polymorphisms, SNPs) have been the focus of several recent studies and
      are gaining much attention. We have conducted a literature search for studies in
      which the lowering of ambient blood pressure by specific drugs or drug classes in
      humans was related to specific genotypes. Twenty-eight studies were identified,
      of which six had a single-dose design, and the remaining 22 studied drug effects
      after more than 4 weeks of drug administration. Virtually all were association
      studies. Prospective trials that compared the prognostic value of genetic methods
      to routine clinical practice were not identified. Almost all studies used a
      candidate-gene design, usually with a very small number of SNPs (typically one).
      Gene-gene and gene-environment interactions were studied only rarely. Only one
      study targeted genes involved in drug metabolism. Most candidate-genes were part
      of the renin-angiotensin system. By far the most extensively studied has been the
      angiotensin-converting enzyme insertion/deletion polymorphism (15 studies) but,
      to date, no clear picture has emerged for this or other genetic variants. Thus,
      the potential for utility of genetic characterization of individual patients as a
      predictor of anti-hypertensive response has yet to be realized.

PMID- 14646690
TI  - Allelic variants of cytochromes P450 2C modify the risk for acute myocardial
      infarction.
AB  - SUMMARY: Cytochromes P450 (CYP) 2C8 and 2C9 are polymorphic enzymes responsible
      for the biosynthesis of vasoactive substances from arachidonic acid including
      endothelium-derived hyperpolarizing factor. Inter-individual differences in the
      action of these substances might be important in the pathogenesis of
      cardiovascular diseases such as acute myocardial infarction (AMI) and
      hypertension. This study describes the relationship between genetic variants of
      CYP2C8 and CYP2C9, and morbidity in myocardial infarction in a large Swedish
      patient material. The study included 1172 AMI patients and 1503 control subjects
      (matched by age, sex and residential area) who participated in the Stockholm
      Heart Epidemiology Program (SHEEP). Genotyping was performed by allelic
      discrimination using a 5'-nuclease assay for the CYP2C8 and CYP2C9 variants. To
      estimate associations to AMI risks, odds ratios (OR) with 95% confidence
      intervals (CI) were calculated. The frequencies of CYP2C8*1, 2C8*3, 2C9*1, 2C9*2
      and 2C9*3 variants in the control group were 0.91, 0.095, 0.83, 0.11 and 0.065,
      respectively. The risk of AMI in the female individuals carrying the *2 or *3
      variant alleles of CYP2C9 and that of all individuals carrying the *3 variant of
      CYP2C8 was higher [OR (95% CI): 1.3 (1.0-1.9), P = 0.09; 1.5 (1.0-2.2), P = 0.06
      and 1.2 (1.0-1.5), P = 0.07, respectively] compared to the groups with CYP2C8*1
      and CYP2C9*1. Possession of rare genetic variants of the CYP2C8 and CYP2C9 genes
      in females is associated with a modest increase in risk of AMI. This might be
      related to genetic differences in the formation of endogenous vasoregulating
      eicosanoids.

PMID- 14646691
TI  - Trimipramine pharmacokinetics after intravenous and oral administration in
      carriers of CYP2D6 genotypes predicting poor, extensive and ultrahigh activity.
AB  - OBJECTIVE: The tricyclic antidepressant trimipramine is one of the drugs with the
      most pronounced differences in pharmacokinetics caused by the CYP2D6 genetic
      polymorphism. However, the effect of CYP2D6 genotype on steady state kinetics and
      on bioavailability has not been studied so far. In addition, we were interested
      in trimipramine pharmacokinetics in genetically defined ultra rapid metabolizers.
      METHODS: We studied intravenous and multiple dose oral application of 50 mg
      trimipramine in five, seven, and three healthy volunteers with CYP2D6 genotypes
      predicting deficient, highly active and ultrarapid metabolism. The latter group
      included carriers of one wild-type and one duplication allele. Trimipramine and
      desmethyltrimipramine concentrations were measured by HPLC over a time interval
      of 72 h after intravenous and after one oral application. RESULTS: Both
      bioavailability and systemic clearance significantly depended on CYP2D6 genotype
      with a linear gene dose relationship. Mean bioavailability was 44, 16 and 12% in
      carriers of zero, two and three active genes of CYP2D6, respectively, and the
      corresponding data for systemic clearance were 12.0, 24.2, and 30.3 l/h.
      Consequently, the mean total oral clearances were 27.3, 151, and 253 l/h in poor,
      extensive and ultrarapid metabolizers. CONCLUSIONS: High bioavailability combined
      with low systemic clearance of trimipramine in poor metabolizers of CYP2D6
      substrates results in a very high exposure to trimipramine with the risk of
      adverse drug reactions. On the other hand, the extremely high systemic and
      presystemic elimination may result in sub-therapeutic drug concentrations in
      carriers of CYP2D6 gene duplications with a high risk of poor therapeutic
      response.

PMID- 14646692
TI  - Myeloperoxidase: new polymorphisms and relation with lung cancer risk.
AB  - Myeloperoxidase (MPO) is an haemoprotein that metabolizes tobacco smoke
      procarcinogens such as benzo(a)pyrene and aromatic amines into highly reactive
      intermediates. A polymorphism in the MPO promoter (-463G>A), resulting in lower
      expression, was previously associated with a decrease in lung cancer risk. In
      this study, the MPO gene was analysed for new polymorphisms by denaturing high
      performance liquid chromatography and sequencing on a panel of 48 subjects.
      Subsequently, the association between newly described polymorphisms, the -463G>A
      single nucleotide polymorphism (SNP) and lung cancer risk was investigated in a
      case-control study comprising 245 Caucasian cases and 249 Caucasian controls.
      Genetic polymorphisms were found in exons 2 (V53F), 6 (M251T), 7 (A332V), 11
      (I642L) and 12 (I717V), with allelic frequencies of 6.0%, 1.8%, 1.8%, 0.2% and
      1.8%, respectively. A new polymorphism located in the intron 11 3' splice site
      was found (0.4%). The known -463G>A polymorphism (24.0%) and four new
      polymorphisms in promoter region were also detected. No correlation between these
      new polymorphisms and lung cancer risk was found. For the -463G>A polymorphism,
      no modification of lung cancer risk was observed for either the G/A genotype
      [odds ratio (OR) 1.19; 95% confidence interval (CI) 0.8-1.8] or the A/A genotype
      (OR 0.97; 95% CI 0.4-2.6). Linkage analysis showed a strong disequilibrium
      between -463G>A polymorphism and exonic SNPs. However, the distribution of
      reconstructed haplotypes did not differ significantly between cases and controls.
      Further studies need to be performed to investigate the role of these
      polymorphisms in others diseases.

PMID- 14646693
TI  - Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype
      dependent renal clearance of irinotecan.
AB  - We performed comprehensive haplotyping of ABCB1/MDR1 gene blocks using 49 genetic
      polymorphisms, including seven novel ones, obtained from 145 Japanese subjects.
      The ABCB1/MDR1 gene was divided into four blocks (Blocks -1, 1, 2, and 3) based
      on linkage disequilibrium analysis of polymorphisms. Using an expectation
      maximization based program, 1, 2, 8, and 3 haplotype groups (3, 12, 32, and 18
      haplotypes) were identified in Blocks -1, 1, 2, and 3, respectively. Within Block
      2, haplotype groups *1, *2, *4, *6, and *8 reported by Kim and colleagues (Clin
      Pharmacol Ther 2001; 70:189-199) were found, and additional three groups (*9 to
      *11) were newly defined. We analyzed the association of haplotypes with the renal
      clearance of irinotecan and its metabolites in 49 Japanese cancer patients given
      irinotecan intravenously. There was a significant association of the *2 haplotype
      in Block 2, which includes 1236C>T, 2677G>T and 3435C>T, with a reduced renal
      clearance of those compounds. Moreover, tendencies of reduced and increased renal
      clearance were also observed with *1f in Block 2 and *1b in Block 3,
      respectively. These findings suggest that the P-glycoprotein encoded by
      ABCB1/MDR1 in the proximal tubules plays a substantial role in renal exclusion of
      drugs and, moreover, that block-haplotyping is valuable for pharmacogenetic
      studies.

PMID- 14646694
TI  - Successful amplification of extremely GC-rich promoter regions using a novel
      'slowdown PCR' technique.
AB  - OBJECTIVES: PCR has become a routine technique in DNA genotyping for diagnostic
      or pharmacogenetics purposes. Promoter regions of genes are in the main focus for
      detecting novel regulatory single nucleotide polymorphisms (rSNPs). However, due
      to very high GC content PCR setup procedures can be very time consuming and not
      infrequently amplification of the regions of interest fail. METHODS: We developed
      a novel method termed 'Slowdown' PCR which allows the successful amplification of
      extremely GC-rich (> 83%) targets. The method relies on combination of a novel
      standardized cycling protocol with varying temperature ramping rates plus the
      addition of 7-deaza-2'-deoxyguanosine, a dGTP analogue. Moreover, we provide
      essential practical hints for optimal primer and template length design for such
      GC-rich targets. RESULTS: Using this setup we successfully amplified and
      sequenced GC-rich DNA regions such as the 5'-upstream regions of the genes GNAS1
      and GNAQ as well as exon1 of the BRAF gene which could not be amplified by
      others. CONCLUSION: Here we show that 'Slowdown' PCR is a versatile method not
      only for amplification of extremely GC-rich regions but also for routine DNA
      diagnostics and pharmacogenetics for templates with different annealing
      temperatures.

PMID- 14646695
TI  - ADRIS--The Adverse Drug Reactions Information Scheme.
AB  - Under the Adverse Drug Reactions Information Scheme (ADRIS) data and knowledge
      relevant to the etiology of adverse drug reactions (ADRs) such as chemical
      structure of parent compounds, metabolites, covalent adducts, nucleic acid and
      protein sequences, protein structures, pharmaco-, toxico- and enzyme kinetics,
      pharmaco- and toxicodynamics, protein interactions, molecular pathways and
      complexes, as well as toxicological and clinical outcomes, are collected and
      logically and semantically related. ADRIS reflects the ontological prerequisite
      for the creation of databases and knowledge discovery systems for the abstraction
      and visualization of theragenomic concepts. A final outcome is the prediction of
      ADRs based on a profound knowledge of drug function and the molecular basics for
      personalized drug safety and eventually, personalized medicine.

PMID- 14646697
TI  - The surgery of the osteo-arthritic hip.

PMID- 14646699
TI  - Fractures of ceramic bearings: history and present status.
AB  - During a period of 25 years (1977 to 2001), 13 fractures of an alumina component
      were recorded retrospectively. During the same period, approximately 5500 alumina
      components were implanted (3300 with all-alumina bearings and 1200 with alumina
      on-polyethylene). These events occurred in seven women and six men, with a mean
      age of 59 years and a mean weight of 71 kg. There were eight fractures of the
      femoral head and five fractures of the socket component. Three fractures clearly
      were related to trauma (two fractures of the socket and one fracture of the head)
      and two were related to an abnormal design (one 22-mm head and one extra-long
      neck). Five fractures occurred without any rational explanation, but two
      fractures that occurred in the early phase could have been caused by a weaker
      alumina material. Finally three recent fractures of the liner were related to a
      change in the design of the material. This has been corrected and no additional
      fractures were observed. Although this dramatic event is of concern, it is
      infrequent and easy to solve by a limited revision procedure if done emergently.
      This rare complication should be balanced with the other complications of THR,
      including mechanical failures and osteolysis, often described with metal-on
      polyethylene prostheses.

PMID- 14646700
TI  - Three-dimensional shape of the dysplastic femur: implications for THR.
AB  - This study evaluates the three-dimensional anatomy of the femur with congenital
      dysplasia of the hip (CDH) in comparison with healthy controls. Computed
      tomographic scans were obtained from 207 women (154 with dysplasia; 54 healthy
      controls) with an average age of 51.6 years (range, 18-82 years). Most of the
      dysplastic joints were classified as Crowe I (43%), or Crowe II or III (48%),
      with 9% Crowe IV. Individualized three-dimensional computer models of the femur
      were generated by reconstruction of the CT scans. Dimensional and morphometric
      parameters were derived by computer analysis of each of the femoral
      reconstructions. The dysplastic femurs had shorter necks and smaller, straighter
      canals than the controls. The shape of the canal became more abnormal with
      increasing subluxation. Detailed analysis showed that the primary deformity of
      the dysplastic femur is rotational, with an increase in anteversion of 5 degrees
      to 16 degrees, depending on the degree of subluxation of the hip. The rotational
      deformity of the dysplastic femur arises within the diaphysis between the lesser
      trochanter and the isthmus and is not attributable to a torsional deformity of
      the metaphysis. This study shows that there is a significant difference in the
      geometry of the normal femurs and those with CDH, even in mild cases. In CDH
      cases, we recommend the use of modular or specially-designed components to
      accommodate the shape of the dysplastic canal.

PMID- 14646701
TI  - Induction of bone ingrowth from acetabular defects to a porous surface with OP-1.
AB  - Reliable ingrowth of bone into porous-coated cementless total hip components can
      be expected in primary surgery. In the revision scenario, however, bone
      deficiency frequently is encountered and the remaining bone may have less
      ingrowth potential. Allograft bone and bone graft substitutes may be successful
      in healing bone defects, but have virtually no capacity to induce bone growth
      from the defect into the porous surface. To evaluate the role osteoinductive bone
      proteins may play in enhancing bone ingrowth, six canines had bilateral total hip
      arthroplasties with a cementless press-fit porous-coated acetabular component. A
      defect 8 mm in diameter and 5 mm in depth was created in the superior
      weightbearing area of each acetabulum. One defect in each animal was filled with
      recombinant human osteogenic protein-1. Each contralateral defect was filled with
      allograft bone, left empty (defect healing control), or no defect was created
      (intact) to serve as a control for ideal conditions for bone ingrowth. The
      osteogenic protein-treated defects healed more completely than allograft bone
      treated or empty defects and achieved a bone density equivalent to the intact
      acetabulum. Bone ingrowth also occurred to a significantly higher degree in the
      osteogenic protein group compared with the allograft or empty defects achieving a
      degree of ingrowth equivalent to the intact acetabulum controls. The osteogenic
      bone protein was successful in achieving complete defect healing and inducing
      extensive ingrowth from the defect into the adjacent porous coating.

PMID- 14646702
TI  - The efficacy of BMP-2 to induce bone ingrowth in a total hip replacement model.
AB  - The purpose of this canine total hip arthroplasty (THA) study was fourfold: (1)
      to quantify the efficacy of rhBMP-2 in a carrier (alphaBSM) versus alphaBSM
      alone, and versus untreated controls to induce bone formation across a defect
      between a porous acetabular component and host bone; (2) to quantify whether
      rhBMP-2/alphaBSM improves bone growth into the porous surface beneath that
      defect; (3) to quantify the efficacy of rhBMP-2/alphaBSM in inducing bone
      ingrowth into the porous layer at points of intimate bone-implant contact; and
      (4) to determine whether rhBMP-2/alphaBSM placed in the lateral uncovered aspect
      of the porous acetabular component promotes de novo bone formation. Fifteen dogs
      were sacrificed 12 weeks after uncemented THA. Five dogs received rhBMP
      2/alphaBSM, five dogs received alphaBSM, and five dogs were controls. In contrast
      to the controls in which no bone filled the defect, the rhBMP-2/alphaBSM induced
      defect filling and full bone formation in the underlying porous coating. The
      alphaBSM produced an intermediary response. However, no increase in new bone
      formation occurred at sites of intimate bone porous surface contact. Recombinant
      bone morphogenetic protein-2/alphaBSM promoted defect filling and bone ingrowth
      into the porous coating beneath the defect region, both of potential value in
      future total joint replacement surgery.

PMID- 14646703
TI  - Demographic factors affecting long-term outcome of total hip arthroplasty.
AB  - We report the outcome of total hip arthroplasty (THA) in a cohort of patients
      with complete long-term radiographic and clinical followup information from our
      database of more than 48,000 primary hip replacements. The purpose of the study
      was to evaluate the influence of various demographic factors and patient
      comorbidity (Charnley classification) on the long-term outcome of THA. The cohort
      was comprised of 25,990 total hip replacements (THRs) in 10,243 (46.6%) men and
      11,754 (53.4%) women with a median age of 66 years (range, 20-96 years) at the
      time of arthroplasty. Our study confirmed that THA has an impressive efficiency
      and reliability in alleviating pain and improving function for almost all of the
      patients. Furthermore, the results are enduring with more than 90% of patients
      being satisfied with the outcome at 15 years. Clinical outcome measures reach
      their maximum at 2 to 5 years after arthroplasty and thereafter they decline
      gradually. Furthermore, patient age, gender, body mass index, and main diagnosis
      all have an influence on specific functional parameters. The Charnley
      classification has the most profound effect on the overall functional status of
      patients.

PMID- 14646704
TI  - Treatment of femoral head osteonecrosis using bone impaction grafting.
AB  - Even in extensive osteonecrosis of the femoral head in younger patients, a
      femoral head-preserving method is preferable. We developed a new technique using
      the lateral approach as used in traditional core biopsy; the osteonecrotic lesion
      was removed and impacted bone grafts were used to regain sphericity and prevent
      collapse. In this prospective one surgeon study, we included 28 consecutive hips
      in 27 patients with extensive osteonecrotic lesions (ARCO classification Stage 2
      [11 hips], Stage 3 [14 hips]; and Stage 4 [three hips]); 14 hips had preoperative
      collapse. The mean age of the patients was 33 years (range, 15-55 years). At a
      mean followup of 42 months (range, 24-119 months), eight hips (29%) were
      converted to a total hip arthroplasty (THA). Of the 20 reconstructions that were
      in situ, 18 were clinically successful (90%) and 70% were radiologically
      successful. Patients who were younger than 30 years at surgery had a
      radiologically significant better outcome, even patients with higher stages of
      osteonecrosis. Patients with preoperative collapse and use of corticosteroids had
      disappointing results. This method is attractive as a salvage procedure, is
      relatively simple and quick, and it does not interfere with an eventual future
      hip arthroplasty.

PMID- 14646705
TI  - Outcome of nonvascularized bone grafting for osteonecrosis of the femoral head.
AB  - Osteonecrosis is a disease with a wide-ranging etiology and poorly understood
      pathogenesis seen commonly in young patients. Various head-preserving procedures
      have been used for this disease to avert the need for total hip replacement.
      These include various vascularized and nonvascularized bone grafting procedures.
      We will describe the use of bone-grafting through a window at the femoral head
      neck junction for the treatment of osteonecrosis of the femoral head. Bone
      morphogenetic protein (BMP)-enriched allograft was used to avoid donor site
      morbidity. Nineteen patients (21 hips) were followed up for a mean of 48 months
      (range, 36-55 months) after a bone grafting procedure in which the diseased bone
      was replaced by a bone graft substitute (combination of demineralized bone
      matrix, processed allograft bone chips, and a thermoplastic carrier). Eighteen of
      21 hips (86%) were clinically successful at latest followup. Two of these
      patients have minimal radiographic progression (< 2 mm head collapse). This
      procedure is straightforward technically, led to low morbidity, and did not
      necessitate procurement of donor site bone graft. This procedure may be effective
      at avoiding or forestalling the need for total hip arthroplasty in young patients
      with early to intermediate stages of osteonecrosis of the femoral head.

PMID- 14646706
TI  - Femoral head resurfacing for the treatment of osteonecrosis in the young patient.
AB  - We reviewed the clinical and radiographic results of 29 consecutive femoral head
      resurfacing procedures in 28 patients with avascular necrosis done from February
      1997 until April 2000. There were 18 males and 10 females with an average age of
      31.6 years (range, 12-48 years). The average Harris hip score significantly
      improved from 48.1 points preoperatively to 79.3 points at last followup. At
      final followup, 17 patients (18 hips [62%]) reported feeling much better or
      better than they did before hemiresurfacing. The overall survivorship was 75.9%
      at 3 years. Eight hips (27.6%) were converted to a total hip arthroplasty (THA)
      at an average 18 months (range, 8-43 months) after resurfacing. The results of
      this study suggest that femoral head resurfacing in a young patient with ON can
      greatly improve symptoms. The majority of patients were satisfied with the
      procedure but outcomes are unpredictable with only 62.5% of patients reporting
      satisfaction and good pain relief at last followup. We continue to offer this
      procedure in young patients with large necrotic lesions with the understanding
      that this procedure provides somewhat unpredictable pain relief; however,
      hemiresurfacing avoids the negatives associated with a bearing surface.

PMID- 14646707
TI  - Long-term results of alumina-on-alumina hip arthroplasty for osteonecrosis.
AB  - Alumina-on-alumina bearings in THR may, in theory, provide an effective answer to
      osteolysis in young patients with ON of the femoral head. The purpose of this
      retrospective study was to report the long-term results of a series of 52
      consecutive alumina THAs (41 patients) done for ON. The mean age of the patients
      at surgery was 41 years (range, 22-79 years). Cemented femoral stems with a 32-mm
      alumina head were used. Plain alumina cups were used and were either cemented (39
      hips) or press-fit (13 hips). No patients were lost to followup. Sixteen hips
      have been revised. Aseptic loosening of the socket was the main cause of failure.
      At an average 16-year followup (range, 11-23.65 years), 26 hips were rated
      excellent and one hip was rated good. No osteolysis was observed and wear was
      undetectable. If revision for aseptic loosening was the end point, the rate of
      survival was 88.5% at 10 years for the socket and 100% at 10 years for the stem.
      With the alumina-on-alumina hip replacement done for ON, absence of osteolysis
      can be expected for as many as 24 years after the operation. New methods of
      socket fixation now are being explored.

PMID- 14646708
TI  - Femoroacetabular impingement: a cause for osteoarthritis of the hip.
AB  - A multitude of factors including biochemical, genetic, and acquired abnormalities
      may contribute to osteoarthritis of the hip. Although the pathomechanism of
      degenerative process affecting the dysplastic hip is well understood, the exact
      pathogenesis for idiopathic osteoarthritis has not been established. Based on
      clinical experience, with more than 600 surgical dislocations of the hip,
      allowing in situ inspection of the damage pattern and the dynamic proof of its
      origin, we propose femoroacetabular impingement as a mechanism for the
      development of early osteoarthritis for most nondysplastic hips. The concept
      focuses more on motion than on axial loading of the hip. Distinct clinical,
      radiographic, and intraoperative parameters can be used to confirm the diagnosis
      of this entity with timely delivery of treatment. Surgical treatment of
      femoroacetabular impingement focuses on improving the clearance for hip motion
      and alleviation of femoral abutment against the acetabular rim. It is proposed
      that early surgical intervention for treatment of femoroacetabular impingement,
      besides providing relief of symptoms, may decelerate the progression of the
      degenerative process for this group of young patients.

PMID- 14646709
TI  - Results of uncemented cups: a critical appraisal at 15 years.
AB  - One of the most important advances in total hip arthroplasty is the development
      of successful cementless acetabular components. Cemented acetabular components in
      older patients showed increasing loss of fixation after the first decade.
      Loosening commonly occurred during the first decade in young patients and after
      revision surgeries. Although some cementless designs failed, the hemispheric
      design with a porous exterior surface now is adopted widely. Assessment of
      acetabular reconstructions should be evaluated as primary operations in the older
      age group, primary operations in younger patients, and revisions. In all three
      categories, the cementless hemispheric design has proven remarkably successful.
      For example, a compilation of three reports on acetabular revisions using the HGP
      design revealed that by 12.5 years, only five of 263 shells required shell re
      revision (2%). Periprosthetic osteolysis and dislocation are problems, but are
      being addressed by improved articulations and designs. These advances are
      remarkable in generating successful long-term acetabular reconstructions.

PMID- 14646710
TI  - Highly cross-linked polyethylene in cemented THA: randomized study of 61 hips.
AB  - Highly cross-linked polyethylene (PE) has been introduced as an alternative
      bearing material in total hip arthroplasty (THA) because of high wear resistance
      in laboratory tests but the clinical experience of this material is limited. We
      evaluated a highly cross-linked PE (warm irradiated adiabatic melting, absorbed
      dose, 95 kGy) in a randomized study of cemented THAs. Cups of the same design but
      made of conventionally gamma irradiated PE (absorbed dose, 25-40 kGy) constituted
      the control group. Sixty-one hips (30 women, 30 men) with a median age of 55
      years (range, 35-70 years) were included. All patients received a Spectron stem
      with 28-mm CoCr head. Radiostereometric examinations with the patient supine or
      standing were done at regular intervals. Wear was measured with the patient in
      the supine position from the first postoperative week, whereas examinations done
      with the patient standing were initiated 3 months after the operation. Dual x-ray
      absorptiometry and conventional radiography were used to evaluate the bone
      mineral density and the radiolucencies around the acetabular component. Fifty-two
      patients (53 hips; 25 highly cross-linked, 28 control) have been followed up for
      2 years. At the 2-year followup, the highly cross-linked cups showed 50%
      reduction of proximal wear compared with the control group, when the patients
      were studied standing. When evaluated supine, the difference in proximal wear did
      not reach significance. The migration of the socket, the relative changes of
      periprosthetic bone mineral density, and the progression of radiolucencies
      between the immediately postoperative followup and 2-year followup did not
      differ. Highly cross-linked PE showed increase resistance to wear. Different
      mechanical properties of the two types of PE studied did not alter the
      performance of the cup in terms of fixation, periprosthetic bone loss, and
      radiographic appearance. However, the followup is short and these results are
      preliminary.

PMID- 14646711
TI  - Metal degradation products: a cause for concern in metal-metal bearings?
AB  - In the majority of patients, orthopaedic implants are biocompatible. However,
      there is an increasing recognition that, in the long-term, permanent orthopaedic
      implants may be associated with adverse local and remote tissue responses in some
      individuals. These adverse effects are mediated by the degradation products of
      implant materials. The recent reintroduction of metal-on-metal bearings for total
      hip arthroplasty has heightened concerns about the biologic response to metal
      degradation products in light of the fact that the serum and urine metal
      concentrations in patients with these implants typically are higher than those
      seen in patients with conventional metal-on-polyethylene bearings. From previous
      studies of long-term metal-on-metal McKee-Farrar implants, it seems that these
      elevated levels may persist for the duration of the implant's lifetime. This is
      of particular concern in the younger and more active patient in whom life
      expectancy after implantation may exceed 30 years. The association of metal
      release from orthopaedic implants with any metabolic, bacteriologic, immunologic,
      or carcinogenic toxicity currently remains conjectural because cause and effect
      have not been established in human subjects. However, continued surveillance of
      patient populations with metal implants, particularly those with metal-metal
      bearings, is warranted.

PMID- 14646712
TI  - Long-term function after Charnley total hip arthroplasty.
AB  - The purpose of this study was to report the functional results and mortality
      rates of a consecutive series of patients younger than 50 years after Charnley
      total hip arthroplasty. The original group of 69 patients (93 hips) was followed
      up until death or a minimum of 25 years after surgery. Of the original 93 hips,
      29 had been revised at some point. Functional outcomes included the Short Form
      36, Western Ontario and McMaster University University Osteoarthritis Index
      (WOMAC), 6-minute walk distance, Noyes activity scale, and Harris hip scores and
      included followup in 42 of 43 living patients. The functional outcome of patients
      was good, with comparable Short Form-36 scores compared with normative values of
      healthy age-matched subjects. The 6-minute walk distances and WOMAC scores were
      slightly lower than healthy normatives but were thought to be influenced by
      medical comorbidities. Although comorbid medical and musculoskeletal conditions
      significantly hindered most measures of function, revision surgery or
      radiographic loosening of components had no significant influence on function.
      The mortality rates of this cohort of patients were similar to normative values
      at both 10 and 25 years after surgery.

PMID- 14646713
TI  - Clinical consequences of stress shielding after porous-coated total hip
      arthroplasty.
AB  - From a series of 223 extensively porous-coated total hip arthroplasties, 208 hips
      had radiographic followup at a minimum of 2 years, which could be evaluated for
      radiographic evidence of stress-shielding. These patients had a mean 13.9-year
      followup (range, 2-18 years). We compared the outcome of 48 total hip
      arthroplasties that had radiographically evident stress-shielding with 160 total
      hip arthroplasties that did not have radiographically visible stress-shielding or
      that had less severe stress-shielding. Stress-shielding was more likely in
      females, patients with a low cortical index, and patients with larger stems. At
      the most recent followup, patients with stress-shielding had a lower mean walking
      score than patients without stress-shielding and less osteolysis. No patients
      with stress-shielding had femoral loosening, implant fractures, or loss of porous
      coating. The revision rate was 13% (six hips) among hips with stress-shielding
      and 21% (33 hips) among hips without stress-shielding. Fifteen-year survivorship
      was 93% among hips with stress-shielding and 77% among hips without stress
      shielding. Stress-shielding did not produce adverse consequences in these
      extensively porous-coated total hip arthroplasties.

PMID- 14646714
TI  - Osteolysis of the pelvis: evaluation and treatment.
AB  - Osteolysis of the pelvis is a common and well-recognized complication associated
      with total hip arthroplasty. The diagnosis and treatment of osteolysis of the
      pelvis is a challenging and controversial problem. Osteolysis of the pelvis often
      is asymptomatic and does not present with symptoms until considerable bone loss
      and loosening of the acetabular socket occur. Radiographs are the most common way
      to detect and monitor osteolysis around an implant. However, lesions viewed
      radiographically usually are underestimations of the lesions found
      intraoperatively. Moreover, some advocate computed tomography scanning to
      evaluate these lesions. The indications for treatment of osteolysis with cemented
      acetabular components are defined more clearly than with a cementless component.
      If the cemented or cementless acetabular component is loose, then revision is
      necessary. However, it is less clear when to intervene surgically with a well
      fixed cup with osteolysis. Many early reports advocated the removal of a well
      fixed socket during revision surgery for osteolysis and polyethylene wear.
      However, the removal of a well-fixed socket has the potential for significant
      damage and loss of the surrounding bone resulting in loss of integrity of a
      column or pelvic discontinuity, which may compromise placing another acetabular
      component. Recently, a new treatment strategy of retaining a well-fixed socket,
      exchanging the liner, and grafting lesions has proven successful. Without the
      removal of the acetabular shell, different techniques are needed to graft the
      osteolytic lesions. Osteolysis is a difficult problem; however, with radiographic
      surveillance to monitor patients for lesions, proper indications, and good
      surgical techniques, the treatment of osteolysis of the pelvis can result in a
      well-functioning total hip arthroplasty.

PMID- 14646715
TI  - Impacted cancellous graft plus cement in hip revision.
AB  - Revision of the femoral component is difficult in the presence of large cavitary
      defects of the femur. Impaction cancellous grafting used in conjunction with a
      cemented prosthesis has been recommended as a means of restoring bone stock while
      providing excellent and durable clinical results. Fifty-seven consecutive femoral
      revisions were done between 1993 and 1997 in 54 patients (24 men and 30 women)
      using the impaction grafting technique and a collarless, tapered, polished stem.
      Strut allografts were used for femoral reinforcement in 40 hips. No patient was
      lost to followup. One patient had an infection develop and had a resection
      arthroplasty. Three patients died of causes unrelated to the hip. After 6.3 years
      the clinical results were excellent. Radiographic evaluation showed no evidence
      of loosening in any of the 53 surviving hips. Subsidence of 1 to 3 mm was seen in
      40 hips and subsidence of 4 to 6 mm was seen in two hips. Cancellous remodeling
      was observed in 42 hips. The most common complications were postoperative femoral
      fractures. All six fractures occurred at the distal end of the prosthesis, were
      not associated with prosthetic loosening, and were treated successfully with open
      reduction and internal fixation without prosthetic revision. These satisfactory
      results and the limited subsidence observed in our patients radiographs could be
      explained by the careful attention to the technical details of the procedure.
      However, even with the generous use of strut graft augmentation, postoperative
      femoral fractures remain our most serious complication.

PMID- 14646716
TI  - Bone graft for revision hip arthroplasty: biology and future applications.
AB  - Revision total hip arthroplasty often presents surgeons with difficult bone loss
      problems. The selection of an appropriate bone graft is influenced by the size of
      the bone defect, the location, the biology of the bone graft site, and whether
      the graft is required for structural support. Autogenous bone graft remains the
      gold standard bone graft material but there only is a limited amount available
      and there is morbidity associated with the harvesting of these grafts. The most
      frequently used bone graft materials include autogenous iliac crest bone graft,
      cancellous allograft chips, demineralized bone matrix, and bulk structural
      allografts (femoral head, distal or proximal femoral allograft, whole acetabuli,
      and femoral strut grafts). It often is difficult to determine on plain
      radiographs whether nonstructural grafts actually incorporate into the host bone.
      Recently, attention has focused on the use of new materials for bone grafting
      including: new demineralized bone matrices, ceramics, autologous platelet
      concentrates, recombinant proteins, and stem cells. The purpose of this review
      was to assess the biologic potential of these nonstructural grafts in revision
      hip arthroplasty and their limitations. Are these agents actually incorporating
      into host bone? Future bone graft options, including tissue engineering and gene
      therapy will be discussed briefly.

PMID- 14646717
TI  - Osteoinductive agents in reconstructive hip surgery: a look forward.
AB  - The use of autograft and allograft material to restore bone stock and promote
      healing and implant stabilization is a crucial part of total hip arthroplasty,
      especially in the revision situation. Recent research has centered on the use of
      osteoinductive materials such as osteogenic proteins or bone morphogenetic
      proteins to promote bone formation. These proteins are members of the
      transforming growth factor-beta superfamily of proteins that either alone or in
      combination with other regulatory molecules induce new bone formation. The
      cloning and genetic expression of recombinant human bone proteins has led to
      production of quantities sufficient for their clinical development. Preclinical
      studies have shown that the osteoinductive capacity of autograft and allograft
      bone can be improved with the addition of osteogenic proteins. Although these
      proteins are effective alone, their use with cancellous and cortical allograft
      and autograft consistently improved the amount and rate of new bone formation
      compared with graft alone resulting in earlier graft incorporation and
      consolidation. When placed in defects adjacent to porous acetabular components,
      the use of an osteogenic protein resulted in earlier defect healing and improved
      component fixation by the enhancement of bone ongrowth and ingrowth. Although no
      detailed clinical studies have been reported to date, an anecdotal report of
      their use with and without bone graft indicate results consistent with those
      obtained in preclinical studies.

PMID- 14646718
TI  - Revision total hip arthroplasty: the limits of fully coated stems.
AB  - Femoral revision with a 7-inch or 8-inch fully porous-coated stem may not provide
      reliable long-term results in patients with moderate bone loss. The purpose of
      this study was to evaluate the limits of fully porous-coated stems and to create
      a treatment algorithm for femoral deficiencies. Fifty-one patients with either a
      10-inch or 9-inch calcar fully porous-coated stem, 10 patients with impaction
      bone grafting, and 10 patients with a modular tapered stem were evaluated at an
      average 4.2 years postoperatively. The mechanical failure rate among the 9-inch
      and 10-inch fully porous-coated stems was 0% in Type III B defects with femoral
      canals less than 19 mm (15 patients), 18% in Type IIIB defects with femoral
      canals greater than 19 mm (2 of 11 patients) and 37.5% in Type IV defects (three
      of eight patients). There were no mechanical failures observed among the bone
      packing or modular tapered stems. Patients with Type IIIB defects and a femoral
      canal less than 19 mm can be treated successfully with either a 10-inch or 9-inch
      calcar fully porous-coated stem. However, patients with Type IIIB defect and an
      endosteal canal greater than 19 mm or a Type IV defect require alternative
      methods of reconstruction such as a modular tapered stem or a bone packing
      procedure.

PMID- 14646719
TI  - Extended trochanteric osteotomy via the direct lateral approach in revision hip
      arthroplasty.
AB  - A review of the results of the extended trochanteric osteotomy through a modified
      direct lateral approach in revision total hip arthroplasty was done. We reviewed
      44 patients (45 procedures) at a minimum of 2 years followup (mean, 3.8 years;
      range, 2.1-7.2 years). There were 26 men and 18 women with a mean age at the time
      of surgery of 70.8 years (range, 36.9-90.4 years). Indications for use of the
      trochanteric osteotomy included facilitation of cement removal (25 procedures),
      proximal femoral varus deformity (14 procedures), trochanteric malposition (five
      procedures), and previous trochanteric osteotomies with significant bony
      overgrowth (three procedures). The mean length of the osteotomy was 133.9 mm. The
      mean migration of the osteotomized fragment was 2.1 mm (range, 0-20 mm) with
      significantly more proximal migration seen with the use of cerclage wires when
      compared with cables. There were two cases of trochanteric escape, for which the
      patients required repeat open reduction internal fixation. There were two late
      fractures of the greater trochanter. One femoral component had early subsidence
      for which the patient required re-revision with a further extended trochanteric
      osteotomy. The mean time to union of the remaining 40 hips was 10.3 months
      (range, 6-24 months). There only was one dislocation postoperatively. The
      extended trochanteric osteotomy through the modified direct lateral approach in
      revision total hip arthroplasty is a reproducible and reliable technique with a
      lower dislocation rate but a higher incidence of trochanteric fracture and escape
      than previously described with its use in the posterior approach.

PMID- 14646720
TI  - Acetabular liner fixation by cement.
AB  - Many situations in revision THA require the exchange of a PE liner in the setting
      of a well-fixed cementless acetabular shell. Unfortunately, a replacement liner
      is not always available, the locking mechanism of the metal shell may be damaged
      or incompatible with the desired liner, or the shell is malpositioned. Revision
      of a well-fixed cementless acetabular shell has been associated with considerable
      morbidity. This raises several questions: can a new PE liner be fixed in the
      existing shell using bone cement, and if so, which techniques can improve the end
      result, and in which patients should they be used? Biomechanical testing of
      cemented PE liners has shown initial fixation strengths that exceed conventional
      locking mechanisms. It is not known during what period this initial fixation will
      fail, but clinical reports with followup of as many as 6 years have shown
      survival in approximately 90% of cases. These studies have shown the importance
      of proper patient selection, accurate sizing of the PE liner, careful preparation
      of the substrate of the liner and the shell, and good cement technique. The
      potential advantages of this technique are less surgical morbidity, more rapid
      surgery and patient recovery, the ability to incorporate antibiotics in the
      cement, and more liner options.

PMID- 14646721
TI  - Treatment of Vancouver B3 periprosthetic femur fractures with a fluted tapered
      stem.
AB  - Periprosthetic femur fractures around a hip arthroplasty associated with a loose
      stem and severely deficient or comminuted bone typically have been treated with
      substitution for the proximal femur using an allograft prosthetic composite or a
      tumor prosthesis. Eight patients (mean age, 68 years; range, 34-80 years) with
      Vancouver Type B3 femur fractures were treated with revision using a long modular
      fluted tapered uncemented stem with retention of the proximal femur. Access to
      the failed prosthesis and joint was gained through the fracture or osteotomy and
      soft tissue attachments to the fracture fragments were maintained. One patient
      died within 1 week. The remaining patients were followed up 1 to 2 years (mean,
      1.5 years). At final followup, all patients had stable implants and all acute
      fractures were healed. Marked reconstitution of proximal femoral bone stock was
      observed consistently. All surviving patients were ambulatory and none had more
      than mild pain. The preliminary results of this method show a high rate of stable
      implant fixation and fracture healing with preservation and reconstitution of the
      host femur.

PMID- 14646722
TI  - Total hip arthroplasty using the minimally invasive two-incision approach.
AB  - A new approach to total hip replacement, a minimally invasive two-incision
      technique, was developed; one incision is used for the acetabular component and
      the other incision is used for the femoral component. The first 100 minimally
      invasive two-incision THAs done at my hospital are reported. The complication
      rate in the first 100 cases was 1%: one proximal femoral fracture. There have
      been no dislocations, no failure of ingrowth, no reoperations, and no other
      complications. After the first 12 cases, an outpatient protocol was initiated. In
      the subsequent 88 patients, 75 patients (85%) chose to go home the day of surgery
      and 13 patients (15%) chose to go home the day after surgery. All patients were
      discharged to home, not to other care facilities. There were no readmissions and
      no complications after discharge. Radiographic analysis of the first 30 patients
      showed 91% of the femoral stems in neutral alignment (range, neutral -3 degrees
      valgus). The abduction angle for acetabular components averaged 45 degrees
      (range, 36 degrees-54 degrees). No component migrated or failed to show ingrowth.
      This two-incision minimally invasive THA technique was shown to be safe and
      facilitated a rapid patient recovery; however, this technique is technically
      challenging and only should be attempted after proper hands-on training.

PMID- 14646723
TI  - Computer simulation: how can it help the surgeon optimize implant position?
AB  - Component placement critically affects the performance and longevity of total hip
      replacements (THRs). Because of limitations of observation and anatomic
      orientation imposed by the operative site, selection of the correct size, and
      position of the acetabular and femoral components is best done through
      preoperative planning. Currently, this is done by comparing two-dimensional
      templates of prosthetic components with clinical radiographs; however, this
      method has the inherent limitation that AP and lateral radiographs each provide
      one projection of the pelvis and the femur. Computer technology makes it possible
      to observe implantation of the femoral and acetabular components in three
      dimensions. This approach allows surgeons to template with superior accuracy,
      while providing an intimate view of the fit of the components in the implantation
      site. Additionally, computer routines can predict the functional outcome of a
      preoperative plan before its implementation. Restoration of leg length, center of
      rotation, ROM of the joint during various activities, and points of bony and
      prosthetic impingement can be analyzed preoperatively by the surgeon. This is a
      valuable tool for surgical navigation and surgeon training. With emerging
      technologic advances in surgical technique, computer-based preoperative planning
      tools should prove all the more essential to reliable component placement.

PMID- 14646724
TI  - Effect of radiation, heat, and aging on in vitro wear resistance of polyethylene.
AB  - Radiation cross-linking increases the wear resistance of polyethylene used in
      total hip replacement. Radiation also generates residual free radicals, which are
      detrimental to long-term properties of polyethylene. Two approaches are used to
      stabilize the residual free radicals and terminally sterilize the components. One
      is postirradiation annealing with gas sterilization and the other is
      postirradiation melting with gamma sterilization in nitrogen. The hypothesis of
      the current study is that postirradiation annealing followed by gamma
      sterilization in nitrogen will result in more free radicals in polyethylene than
      gamma sterilization either in air or in nitrogen alone. To test this hypothesis,
      concentration of residual free radicals was quantified in polyethylene that was
      annealed and gamma sterilized in nitrogen and control polyethylenes gamma
      sterilized in air versus in nitrogen. Three crosslinked polyethylenes that were
      melted and gas sterilized also were included in the study. The effects of
      residual free radicals were studied by accelerated aging. Oxidation levels and
      weight loss in bidirectional pin-on-disk tests were determined before and after
      aging. Polyethylene that was subjected to postirradiation annealing and gamma
      sterilization resulted in 58% more residual free radicals than control
      polyethylenes. Weight loss of the annealed polyethylene increased by 16-fold on
      accelerated aging and had three times higher oxidation levels than that measured
      in control polyethylenes after aging. In contrast, polyethylenes that were
      stabilized with postirradiation melting and terminally gas sterilized showed no
      detectable residual free radicals. Accelerated aging did not affect the weight
      loss and oxidation levels of melted polyethylenes.

PMID- 14646725
TI  - Acetabular retroversion is associated with osteoarthritis of the hip.
AB  - Primary osteoarthritis of the hip may have a structural basis. It was
      hypothesized that the radiographic appearance of acetabular retroversion could be
      created by altering the morphologic features of the acetabular walls, and that
      acetabular retroversion, as defined on an anteroposterior radiograph of the
      pelvis, is associated with osteoarthritis of the hip. A model pelvis was used to
      simulate normal, augmented, deficient, and rotated walls of the acetabulum, and
      radiographs were taken to compare the projections of the modified acetabular
      walls with the known plain radiographic appearance of a retroverted acetabulum.
      One hundred thirty-one good quality anteroposterior radiographs of the pelvis
      taken before total hip arthroplasty for idiopathic hip osteoarthritis were
      compared with 99 good quality radiographs taken for nonorthopaedic reasons. The
      prevalence of radiographic acetabular retroversion is 20% among patients with
      idiopathic hip osteoarthritis and 5% among the general population. The appearance
      of acetabular retroversion on an anteoroposterior radiograph of the pelvis is
      created by deficiency of the posterior wall of the acetabulum. There is a
      statistically significant association between radiographic acetabular
      retroversion and hip osteoarthritis. These findings have applicability to
      understanding the mechanical etiology of hip osteoarthritis, and to surgical
      technique during periacetabular osteotomy and total hip arthroplasty.

PMID- 14646726
TI  - Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral
      head.
AB  - Some studies have suggested that thrombotic and fibrinolytic disorders may be
      etiologic causes of osteonecrosis of the femoral head. A case-control study was
      done to determine whether these disorders are associated with osteonecrosis of
      the femoral head in East Asian patients with nontraumatic osteonecrosis of the
      femoral head. Twenty-four consecutive patients who had been diagnosed as having
      nontraumatic osteonecrosis of the femoral head were matched with 24 control
      subjects for gender, age (1-year range), and the time of presentation (1-year
      range). Thrombotic factors including protein C activity, protein S activity,
      antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus
      antibody were investigated. Fibrinolytic factors including tissue-plasminogen
      activator, plasminogen activator inhibitor-1, tissue-plasminogen activator and
      plasminogen activator inhibitor-1 ratio, lipoprotein (a), and plasminogen also
      were investigated. There were no significant differences in the levels of
      thrombotic and fibrinolytic factors. In eight patients with idiopathic
      osteonecrosis, anticardiolipin antibody immunoglobulin G, an antiphospholipid
      antibody which is associated with thrombotic phenomena, was lower than that in
      respective control subjects. These data do not confirm an etiologic role for
      thrombotic and fibrinolytic disorders in East Asian patients with nontraumatic
      osteonecrosis of the femoral head.

PMID- 14646727
TI  - In vivo assessment of patellofemoral joint contact area in individuals who are
      pain free.
AB  - Magnetic resonance imaging was used to quantify in vivo patellofemoral joint
      contact area and to determine if contact area is affected by quadriceps muscle
      contraction. Ten subjects without pain (six women, four men) had their right
      patellofemoral joint imaged. Cartilage-enhanced, axial plane images were obtained
      at 0 degrees, 20 degrees, 40 degrees, and 60 degrees knee flexion under
      quadriceps loaded (contracted) and quadriceps unloaded (relaxed) conditions.
      Medial and lateral facet contact area measurements were obtained on each image,
      and then summed across all images in a series to yield facet contact area
      measurements for each knee angle. Total contact area was computed as the sum of
      medial and lateral facet contact areas. Consistent with in vitro studies,
      progressive increases in patellofemoral joint contact area were observed from 0
      degrees to 60 degrees knee flexion. The lateral facet comprised a greater
      percentage of total contact area compared with the medial facet at each knee
      flexion angle, suggesting increased load-bearing potential. Quadriceps
      contraction did not affect patellofemoral joint contact area indicating that the
      addition of a compressive load to the joint did not alter the area of the load
      bearing surfaces. In vivo assessment of patellofemoral joint contact area could
      provide insight into mechanisms of patellofemoral joint disorders.

PMID- 14646728
TI  - Custom cross-pin fixation of 32 tumor endoprostheses stems.
AB  - The main cause of mechanical failure of primary and revision cemented tumor
      endoprosthetic stems is aseptic loosening. The placement of custom designed pins
      through the bone, the cement, and the stem can create a bone-cement-prosthesis
      composite that resists the rotatory stresses that lead to aseptic loosening. At
      risk situations include large primary reconstructions where the residual short
      metaphyseal articular segments lack sufficient length and cortical contact to
      provide lasting fixation, and revision prostheses that are to be recemented into
      straight diaphyseal segments that already have experienced aseptic loosening.
      Current modular tumor endoprosthetic systems have improved availability and allow
      for some intraoperative flexibility, but they do not provide solutions for these
      at risk scenarios. Additional customization is necessary. We report on the 16
      year experience with 32 custom cross-pin stems at the University of California,
      Los Angeles (UCLA). Twenty of these patients have been followed up for more than
      2 years. There were three mechanical failures, three patients were lost to
      followup, and five patients died of disease. There have been no cases of aseptic
      loosening in this series. Cross-pin fixation has been effective when used in
      carefully selected cases.

PMID- 14646729
TI  - Closed fractures of the proximal tibia treated with a functional brace.
AB  - It generally is agreed that fractures of the proximal tibia, when treated with
      intramedullary nails, are more likely to present technical difficulties and to be
      associated with an increased rate of complications. This study reports on 108
      closed fractures located in the proximal third of the tibia that were treated
      with functional braces. Nonunion occurred in 2.7% of the patients; the final
      displacement and shortening averaged 20% and 3.5 mm, respectively. Eighty-eight
      percent of the fractures healed with less than 6 degrees of angular deformity. It
      seems that functional braces for closed fractures of the tibia, located in its
      proximal third, are a viable therapeutic approach that offers satisfactory
      clinical and radiographic results in a high percentage of instances.

PMID- 14646730
TI  - Low-intensity ultrasound stimulation in distraction osteogenesis in rabbits.
AB  - Low-intensity pulsed ultrasound has been shown to accelerate fracture healing.
      This experiment investigated its possible role in distraction. Thirty-four New
      Zealand White rabbits had distraction osteogenesis, followed by low-intensity
      pulsed ultrasound therapy. Seventeen animals had the ultrasound transducer
      switched off (controls). Four and 6 weeks postoperatively, tibiae were analyzed
      using quantitative computed tomography and four-point mechanical testing. Two
      tibiae from each group had histologic analysis at 4 weeks. No significant
      differences were identified between regenerates of ultrasound-treated and control
      groups with respect to bone mineral content, cross-sectional area, and strength.
      No significant reductions in osteopenia proximal and distal to the regenerate
      were observed. Histologic observation showed no differences in bone volume
      fraction, but ultrasound-treated regenerates appeared to have fewer trabeculae of
      increased thickness, and fewer osteoclasts. The modulation by ultrasound may
      occur by accelerating endochondral ossification through action on chondrocytes,
      yet distraction osteogenesis is largely intramembranous. Although ultrasound is
      proven to be effective in unconstrained systems such as plaster, the current
      study does not support the role of low-intensity pulsed ultrasound as an adjunct
      for patients having distraction osteogenesis in a rigid fixator. Additional
      research is needed to definitively support the use of low-intensity pulsed
      ultrasound in such situations.

PMID- 14646731
TI  - A 35-year-old man with bony deformities and a soft tissue mass.

PMID- 14646732
TI  - Leg pain in an 8-year-old boy.

PMID- 14646733
TI  - Calf mass in a 2-year-old boy.

PMID- 14646735
TI  - Total replacement of the knee using the Freeman-Swanson knee prosthesis. 1973.

PMID- 14646736
TI  - Insall Award paper. Primary TKA in patients with lymphedema.
AB  - Lymphedema is a relatively common disorder; wound and vascular complications
      after orthopaedic surgery are assumed, but not previously shown, to be higher in
      this population. We reviewed the outcome and complications of knee arthroplasty
      in patients with lymphedema, documented by physical examination at their
      preoperative medical assessment. This was a retrospective analysis of
      prospectively collected data compiled on all patients having knee arthroplasty at
      our institution. Eighty-three knee replacements were implanted in 63 patients.
      Patients were followed up for a minimum of 2 years, with a mean followup of 58
      months (range, 24-228 months). No patients were lost to followup. We noted
      significant improvement in the Knee Society score from a preoperative mean of 47
      points (range, 16-75 points) to a postoperative mean of 87 points (range, 53-100
      points). The knee functional score also improved significantly from a
      preoperative mean of 36 points (range, 0-80 points), to a postoperative mean of
      59 points (range, 0-100 points). The total complication rate was 31%, with 10
      superficial wound infections (12%), six deep infections (7%), and three deep
      venous thromboses (3.6%). We concluded that although knee arthroplasty can be
      successful in reducing pain and improving function in patients with lymphedema,
      the complication rate is greater than that seen in patients without this
      diagnosis.

PMID- 14646737
TI  - Predicting total knee replacement pain: a prospective, observational study.
AB  - To describe the natural history of pain after total knee arthroplasty and to
      identify factors predicting excessive postoperative pain, we used a prospective,
      observational study assessing clinical and radiographic variables preoperatively
      and at 1, 3, 6, and 12 months after knee replacement. Data sources included the
      visual analog pain scale and other measures of patient health, psychologic state,
      and component reliability. Regression analyses were conducted to identify
      specific factors predictive of postoperative pain, controlling for inequality of
      variables, and confirmed using regression diagnostics. For 116 patients (149
      knees; mean age, 66 years; 55.2% women), significant pain was reported by 72.3%,
      44.4%, 22.6%, 18.4%, and 13.1%, respectively. No intergroup differences existed
      for anesthesia, weight, age, or gender. Patients with greater preoperative pain
      had more postoperative pain, used more home therapy, and postoperative
      manipulations. Preoperative depression and anxiety were associated with
      heightened pain at 1 year. Pain after knee replacement resolves quickly,
      declining to approximately (1/2) by 3 months. However, one in eight patients
      report moderate to severe pain 1 year after surgery despite an absence of
      clinical or radiographic abnormalities. Development of office-based preoperative
      screening tools and interventions for these patients may reduce postoperative
      costs and improve patient-perceived outcomes.

PMID- 14646738
TI  - Multicenter determination of in vivo kinematics after total knee arthroplasty.
AB  - A summation analysis of more than 70 individual kinematic studies involving
      normal knees and 33 different designs of total knee arthroplasty (TKA) was done
      with the objective of analyzing implant design variables that affect knee
      kinematics. Eight hundred eleven knees (733 subjects) were analyzed either during
      the stance phase of gait or a deep knee bend maneuver while under fluoroscopic
      surveillance. Fluoroscopic videotapes then were downloaded onto a workstation
      computer and anteroposterior (AP) femorotibial translational patterns were
      determined using an automated three-dimensional model fitting technique. The
      highest magnitude of translation was found in the normal and ACL-retaining TKA
      groups. Paradoxical anterior femoral translation during deep flexion was most
      commonly observed in PCL-retaining TKA. Substantial variability in kinematic
      patterns was observed in all groups. The least variability during gait was
      observed in mobile-bearing TKA designs, whereas posterior-stabilized TKA designs
      (fixed or mobile-bearing) showed the least variability during a deep knee bend. A
      medial pivot kinematic pattern was observed in only 55% of knees during deep knee
      flexion. Kinematic patterns of fixed versus mobile-bearing designs were similar
      with the exception of mobile-bearing TKA during gait in which femorotibial
      contact remained relatively stationary with minimal AP femorotibial translation.

PMID- 14646739
TI  - The difficult knee: severe varus and valgus.
AB  - To correct severe varus or valgus deformity, the surgeon must have clear
      knowledge of the location, orientation, and physical characteristics of the soft
      tissue structures that provide stability to the knee. Correct ligament balance
      restores proper load transfer across the knee and minimizes polyethylene wear.
      The failure to adequately release contracted ligaments or the overzealous release
      of ligaments will result in instability and secondary accelerated wear of a total
      knee implant. I describe several methods of selective ligament release of the
      contracted soft tissues that contribute to fixed varus and valgus deformity.

PMID- 14646740
TI  - Genu recurvatum in total knee replacement.
AB  - Genu recurvatum deformities are unusual before total knee arthroplasty (TKA),
      occurring in less than 1% of patients. Because of its rarity, concern may exist
      regarding the recurrence of the deformity and the potential for instability after
      TKA. Recurvatum may be associated with a severe osseous deformity, including genu
      valgum, capsular or ligamentous laxity, and, rarely, neuromuscular disease. In
      the presence of the latter, a plantarflexion contracture of the ankle also may be
      present. Therefore, specific attention should be given preoperatively to
      evaluation of the quadriceps, hamstrings, and gastrocnemius complex. Because genu
      recurvatum is known to recur in patients with certain neuromuscular disorders,
      the etiology of the hyperextension deformity must be elucidated thoroughly before
      surgery. In the absence of neuromuscular disease, however, hyperextension
      deformities tend not to recur after TKA. Care should be taken to avoid even mild
      degrees of residual instability in the coronal plane at surgery because this is
      associated with increased extension in the postoperative period.

PMID- 14646741
TI  - Stiffness and ankylosis in primary total knee arthroplasty.
AB  - To do a successful total knee arthroplasty (TKA), adequate exposure of the tibial
      plateau and distal femur is required. Difficulty with exposure often is
      encountered in the patient with a stiff or ankylosed knee. This can lead to
      complications including component malpositioning and extensor mechanism problems,
      such as patellar tendon rupture. In these cases where the knee has limited motion
      preoperatively, knowledge of advanced techniques for soft tissue treatment, and
      for optimizing exposure are required. Numerous such techniques have been
      described, including the quadriceps snip, V-Y quadriceps turndown, tibial
      tubercle osteotomy, and femoral peel. A systematic review of these techniques,
      including indications and results, based published reports and our experiences,
      is presented.

PMID- 14646742
TI  - The extensor mechanism in total knee replacement.

PMID- 14646743
TI  - The role of patellar resurfacing in total knee arthroplasty.
AB  - The ideal treatment of the patella in primary total knee arthroplasty (TKA) for
      osteoarthritis (OA) remains unclear. Although data exist in the literature to
      support either resurfacing or not resurfacing the patella, evidence continues to
      emerge that unresurfaced patellas deteriorate with time. Recent prospective,
      randomized studies also favor patellar resurfacing over retaining the native
      patella, reporting reoperation rates to convert unresurfaced to resurfaced
      patellas exceeding those for complications after patellar resurfacing. In
      addition, the incidence of residual patellofemoral pain after secondary
      resurfacing is substantially higher than when patellofemoral resurfacing is done
      primarily. Patient selection criteria are critical in the decision-making
      process. Patellofemoral complications, the greatest argument against resurfacing,
      have been diminished with improved surgical techniques and implant design.

PMID- 14646744
TI  - Patellar options in revision total knee arthroplasty.
AB  - There are numerous options that need to be considered by the surgeon at the time
      of revision total knee arthroplasty (TKA). One needs to consider the reason for
      the revision, the type of patella in place, and the length of time the patella
      has been in place. The surgeon also needs to consider the status of the patellar
      bone stock, the stability of the patellar component (well-fixed or loose), and
      the component type (cemented or metal-backed). Assuming that the existing
      prosthesis is not metal-backed and has minimal PE wear, then it is preferable to
      retain a well-fixed all-PE cemented patellar button. However, if the button is
      metal-backed, then it probably is best to remove the button and replace it with
      an all-PE domed patellar component. Assuming more than 8 mm of patellar bone
      stock is remaining, it usually is best to cement an all-PE dome-shaped patella.
      However, if less than 8 mm is remaining, then that patient can be left with a
      patelloplasty, recognizing that this individual is going to continue with a high
      likelihood of anterior knee pain, subluxation, and poor functional results. In
      that situation, it may be preferable to consider a bone stock augmentation.

PMID- 14646745
TI  - Patella fracture after post total knee replacements.
AB  - A retrospective study was done to determine the incidence, clinical function, and
      complications of treatment in a large series of patella fractures after total
      knee replacement (TKR). Between 1983 and 1996, 4583 primary AGC TKRs done at our
      institution. One hundred seventy-seven fractures were identified in 135 patients
      for a fracture incidence of 3.8%. Twenty-two fractures were vertical and had a
      stable implant and intact extension mechanism (Type 1). Twenty-one fractures had
      disruption of the extensor mechanism of less than 1 cm (Type 2A). Seventeen
      fractures had disruption of the extensor mechanism of 1 cm or more (Type 2B). One
      hundred fourteen fractures had a loose component and an intact extension
      mechanism (Type 3). Patients treated nonoperatively generally had no extensor lag
      and had adequate pain and function scores. Patients treated operatively had a
      high complication rate. Four of nine patients treated with excision of an
      extruded patella button developed a deep infection. Both patients treated with
      open reduction internal fixation (ORIF)had a nonunion develop. Surgery on
      patients with patella fractures has a high complication rate and should be
      avoided if possible.

PMID- 14646746
TI  - Treating extensor mechanism disruption after total knee arthroplasty.
AB  - A consecutive series of 14 patients with chronic extensor mechanism disruption
      after total knee arthroplasty (TKA) were treated with allograft reconstruction.
      Preoperatively all patients had full passive extension but a complete extensor
      lag. The average time from extensor mechanism disruption to surgery was 7 months
      (range, 3-24 months). Two methods of reconstruction were used depending on
      specific indications: an Achilles tendon with calcaneal bone block (eight
      patients) or a quadriceps tendon-patella-patellar tendon-tibial tubercle
      composite graft (six patients). At followup averaging 42 months (range, 24-60
      months) all patients were community ambulators, five patients used a cane, two
      patients used a walker, and seven patients used no assistive devices. One patient
      had a partial rerupture and a 45 degrees extensor lag, one patient had a 30
      degrees extensor lag, two patients had a 15 degrees extensor lag, and 10 patients
      had a lag of less than 10 degrees. All patients thought that their functional
      status had been improved and were satisfied with the results of the allograft
      reconstruction.

PMID- 14646747
TI  - Treatment of the patella at reimplantation for septic total knee arthroplasty.
AB  - The results of treatment of the patella at the time of aseptic revision of a
      total knee arthroplasty (TKA) have been better with resurfacing of the patella
      than other modes of treatment such as leaving a bony shell. Treatment of the
      patella at the time of reimplantation of a TKA has not been addressed in prior
      studies. The ability to resurface the patella will be determined by the amount of
      bone remaining, integrity of the patella, vascularity, the location of the joint
      line, and soft tissue coverage for wound closure. The current review addresses
      the technique of patellar resurfacing and patellar bone defect treatment at the
      time of reimplantation of a TKA.

PMID- 14646748
TI  - Scientific program. Total knee replacement.

PMID- 14646749
TI  - Analysis of unicompartmental knee arthroplasty in a community-based implant
      registry.
AB  - Using a unique community implant and explant registry, long-term survival of
      unicompartmental knee arthroplasty was examined and compared with total knee
      arthroplasty (TKA) survival. All patients with unicompartmental knee
      arthroplasties done since September 1, 1991 were followed up prospectively to
      January 31, 2002 to assess survival and reason for revision. Five hundred sixteen
      unicompartmental knee arthroplasties of nine different designs were done by 23
      surgeons. During this period, 39 of the 516 unicompartmental knee arthroplasties
      were revised. The major revision reasons for unicompartmental knee arthroplasties
      were progression of arthritis in the uninvolved compartments (51.3%), aseptic
      loosening (25.6%), and PE wear (20.5%). Kaplan-Meier survival analysis with
      revision as the end point revealed survival of 92.6% (range, 90.0%-95.2%) at 5
      years for these unicompartmental knee arthroplasties and 88.6% (range, 85.0%
      92.2%) at 10 years, compared with 94.8% (range, 93.5%-96.0%) at 10 years for
      primary TKAs. This community registry experience may more accurately reflect the
      results obtained in community practice, with different surgeons, varying
      indications, and numerous designs. The current study showed that revision of
      unicompartmental knee arthroplasties is done most commonly for progression of
      arthritis in the contralateral compartment, and at a higher rate than revision of
      primary cemented TKA.

PMID- 14646750
TI  - Extraarticular abrasive wear in cemented and cementless total knee arthroplasty.
AB  - In this study, we examine the contributions of periprosthetic impingement to a
      seldom recognized source of PE damage resulting in gouging, abrasion, and severe
      localized damage in cemented and cementless total knee replacement. One hundred
      sixty two tibial components of 34 different designs in a retrieval collection
      were examined. The presence and location of abrasive wear to the nonarticulating
      edges of the insert were measured, with representative specimens examined using
      SEM. Significant abrasive wear was observed in 35% of the retrievals with
      cemented femoral components and 25% from noncemented components. Within the group
      of worn inserts, abrasive scars were seen with a frequency of 75% on the extreme
      medial edge, 20% on the extreme lateral edge, 26% on the posteromedial edge, and
      16% on the posterolateral edge. The role of extraarticular impingement in this
      damage mode was confirmed by examination of retrieved femoral components with
      overhanging cement or embedded osteophytes. In the majority of cases, this
      complication may be avoided by careful removal of excess cement and extracortical
      osteophytes.

PMID- 14646751
TI  - Open debridement of acute gram-positive infections after total knee arthroplasty.
AB  - Open debridement and retention of components is an attractive, but often
      ineffective strategy for the treatment of a total knee arthroplasty (TKA) with
      acute infection. Few studies have stratified the outcomes of debridement
      specifically according to bacterial species. Thirty-one TKAs with acute gram
      positive infections, seen at our institution during the past 10 years, were
      treated with open debridement, component retention, and antibiotics. The average
      duration of symptoms before debridement was 9 days (range, 1-40 days), and 78% of
      debridements were done within 10 days of the onset of symptoms. Eleven (35%) of
      the 31 patients successfully retained their components at most recent followup,
      without ongoing infection (mean, 4 years; range, 2-10 years). Only one (8%) of
      the 13 who had an infection with Staphylococcus aureus was treated successfully,
      compared with 10 (56%) of 18 patients who had infections, with either
      Staphylococcus epidermidis or a streptococcal species. The difference between
      these groups is statistically significant. The success rate of debridement of
      acute infections in TKA varies significantly depending on the involved pathogen.
      A high failure rate suggests that immediate component removal should be
      considered in the presence of acute Staphylococcus aureus infection in TKA.
      Debridement for acute streptococcal or Staphylococcus epidermidis species has
      better success, but likely should be done within 2 to 3 days from the onset of
      symptoms.

PMID- 14646752
TI  - Surface damage on open box posterior-stabilized polyethylene tibial inserts.
AB  - Twenty retrieved Scorpio posterior-stabilized implants were available for
      analysis. The mean implantation time was 22 months (range, 2 days-42 months).
      Favorable types and amounts of surface damage were seen on the tibiofemoral and
      backsides of these modular PE liners that had been packaged in an inert
      environment and then sterilized by gamma irradiation. Delamination represented
      only 0.1% of the total surface damage. Off-axis loading (varus malalignment) was
      associated with tibial component loosening but there was no evidence of
      peripheral damage of PE caused by edge loading. With this open-box design,
      hyperextension marks on the anterior aspect of the posterior-stabilized post from
      femoral component impingement occurred in 11 of 20 cases and was related to
      sagittal component positioning: excess tibial slope or increased tibial slope
      combined with a flexed femoral component. Unique coarse abrasions occurred in 16
      of 20 cases and were the result of cement extrusion into the open box, especially
      with varus malalignment. These observations provide guidance for optimizing the
      surgical technique and the design of posterior-stabilized total knee components.

PMID- 14646753
TI  - Total knee arthroplasty for neuropathic (Charcot) joints.
AB  - The clinical and radiographic results of 40 modern design condylar total knee
      arthroplasties (TKAs) in 29 patients with a confirmed diagnosis of Charcot joint
      were reviewed. The followup averaged 7.9 years (range, 2-15 years) for clinical
      and 6.4 years (range, 2-15) for radiographic surveillance. There was a
      significant improvement in Knee Society pain and function scores and ROM after
      knee arthroplasty. Extensive bone fragmentation and bone defect was present in 38
      knees (95%). Metal wedge augments (10 knees, eight patient), autologous bone
      grafting (17 knees, 13 patients), and bone allografts (two knees, two patients)
      were used to reinforce the bony defects. Ligamentous instability necessitated the
      use of long stem components in 27 knees and rotating hinge prostheses in five
      knees. There were six reoperations for periprosthetic fracture (two knees, two
      patients), aseptic loosening (two knees, two patients), instability (one knee,
      one patient), and deep infection (one knee, one patient). Total knee arthroplasty
      may be offered to a select group of patients with end-stage neuropathic
      arthropathy. The basic principles of knee arthroplasty in restoring limb
      alignment, reinforcing bony defects by bone grafting or augmented prostheses,
      careful ligamentous balancing, and appropriate selection of constrained
      prostheses particularly are important in these patients. The technical challenges
      encountered during TKA in patients with neuropathic arthropathy, particularly in
      those with significant deformities, can require skills, implant systems, and
      methods usually reserved for complex revision arthroplasty.

PMID- 14646754
TI  - New techniques and concepts in total knee replacement.

PMID- 14646755
TI  - Unicompartmental tibial hemiarthroplasty: early results of the UniSpacer knee.
AB  - An intra-articular metallic spacer is evaluated for the treatment of isolated
      medial compartment OA. It is proposed that this implant can provide axial
      correction for a varus deformity, eliminate the pseudolaxity of the MCL, improve
      knee function, maintain ROM, and provide pain relief. One-and 2-year data are
      presented on 71 UniSpacer Knee System implants that were implanted in 67 patients
      (four had bilateral surgeries). The mean age and weight of these patients was 54
      years and 94 kg (207 lb), respectively. The heaviest patient in the group weighed
      168 kg (370 lb). All knees were evaluated using the Knee Society clinical rating
      system, Lysholm scoring scale, radiographic limb alignment, and ROM. The mean
      Knee Society knee score improved 169% in the 1-year group and 193% in the 2-year
      group. The mean Knee Society function score improved 31% and 65%, respectively.
      The mean Lysholm score improved 88% and 140%, respectively. Five implants (7%)
      were revised to total knee arthroplasty (TKA) and 10 implants (14%) were revised
      to another UniSpacer Knee System implant. The early results suggest that an intra
      articular metallic spacer is a viable treatment option for OA in the younger
      patient.

PMID- 14646756
TI  - UniSpacer: insufficient data to support its widespread use.
AB  - The concept of a UniSpacer is not new. McKeever and MacIntosh metallic
      hemiarthroplasties have been available for more than 50 years. Two decades ago,
      published reports for patients with unicompartmental OA revealed good initial
      results in 85% of patients. This procedure is conservative and easily revised, if
      necessary, to any type of arthroplasty in the future. The UniSpacer can be
      thought of as a mobile McKeever or MacIntosh metallic hemiarthroplasty. Rather
      than attempting fixation to the tibial plateau via a keel or a roughened
      undersurface, it is designed to translate freely on the tibial plateau as
      determined by the conforming articulation of its top side surface with the
      femoral condyle. This mobility makes it inappropriate for use in the lateral
      compartment where the femoral roll-back could cause prosthetic dislocation or
      soft tissue impingement or both. The eventual role of the UniSpacer in
      arthroplasty currently is uncertain. There are no published reports of its
      effectiveness. Its indication should be similar to those for McKeever
      arthroplasty. A patient with unicompartmental OA in whom an osteotomy is
      contraindicated but is considered too young, heavy, or active for a metal-to
      plastic arthroplasty is ideal. Less than 1% of patients with OA should be
      appropriate candidates. The procedure is technically demanding and sensitive,
      making its widespread success unlikely.

PMID- 14646757
TI  - Optimizing flexion after total knee arthroplasty: advances in prosthetic design.
AB  - The clinical results with most modern total knee arthroplasty (TKA) designs are
      highly satisfactory regarding pain relief and improving walking ability. However,
      one problem that has not been addressed fully by most current designs is the
      ability to consistently achieve flexion greater than 120 degrees. Although the
      human knee is capable of flexion of more than 150 degrees, an analysis of the
      results of contemporary TKA reveals that on average, patients rarely flex beyond
      120 degrees. Key factors influencing range of flexion after TKA include
      preoperative knee motion, surgical technique, prosthetic design, and
      rehabilitation. The success of any total knee system may in part be linked to its
      ability to optimally restore normal kinematic function. Some arthroplasty designs
      currently are available that incorporate modifications aimed at improving range
      of flexion, but limited data currently are available on their function and
      potential advantages. Currently, an in vitro experimental model incorporating
      robotics is being used to investigate the kinematics of the native knee and
      various TKA designs at flexion angles beyond 120 degrees. This robotic model in
      conjunction with clinical studies may provide an understanding of the limitations
      of contemporary knee designs regarding achieving higher degrees of knee flexion.
      This may lead to the refinement of existing designs and development of newer
      prostheses that may enhance the range of flexion that is achievable after TKA.

PMID- 14646758
TI  - Design may be counterproductive for optimizing flexion after TKR.
AB  - Pain-free flexion of as much as 155 degrees with stability is the ultimate goal
      of total knee replacement (TKR). Achieving this amount of flexion depends on
      implant design, surgical technique, preoperative range of motion (ROM), and
      patient cooperation. Current design trends are focusing on shortening the radii
      of curvature; such shortening, in turn, thickens the posterior femoral condyle,
      and increases the height of the posterior-stabilized box, both of which require
      removal of more bone. The end results may be excessive wear, increased
      patellofemoral complications, and difficult revisions. Several studies have
      indicated preoperative ROM is more predictive of postoperative ROM than any other
      criteria, including implant design. Based on currently available information, if
      full or almost full preoperative ROM is required for the high flex total knee
      design, few patients would qualify for the high flex TKA.

PMID- 14646759
TI  - How accurate is current TKR instrumentation?
AB  - Mechanical total knee replacement (TKR) alignment systems have fundamental
      limitations that limit their ultimate accuracy. This study uses an image-free
      computer-assisted navigation system to assess the accuracy of a currently
      available conventional mechanical, intramedullary instrumentation system.
      Mechanical instrumentation allows reasonably accurate and reproducible (within 3
      degrees varus-valgus) frontal and sagittal limb alignment. There is a tendency to
      leave the knee in slight flexion, to hyperextend the femoral component and to
      posteriorly tilt the tibial implant with mechanical AP guides. There also is a
      consistent tendency to internally rotate the femoral implant. Although almost all
      of the 20 TKRs resulted in final limb alignment within 3 degrees of the frontal
      and sagittal mechanical axes, only four TKRs were done in which all of the
      measured steps were within 3 degrees of the optimal positions. If implant
      longevity, pain-relief, and function are related to the accuracy with which TKRs
      are done, this study emphasizes that current mechanical instrumentation does not
      result in a high incidence of accuracy when each step of the procedure is
      measured. Computer-assisted techniques permit measurement of the steps of the
      TKRs procedure with a high degree (error < 1 degree) of accuracy.

PMID- 14646760
TI  - Minimal incision total knee arthroplasty: early experience.
AB  - Total knee arthroplasty (TKA) has evolved during the past 30 years to a well
      defined technical surgery with excellent results for as many as 20 years of
      followup. The concepts of exposure, ligament balancing, and joint alignment have
      been established clearly by Insall and others. In the early 1990s, Repicci
      introduced minimally invasive surgery for unicondylar knee arthroplasty. This
      approach suggested that less invasive surgery could accomplish similar results to
      those of standard unicondylar knee arthroplasty. Early reports in the literature
      support these conclusions. It only was logical that the minimally invasive
      surgery approach eventually would be applied to TKA. It is extremely important to
      establish a clear definition of the minimally invasive surgery and, then, to
      follow the results. We have completed 70 minimally-invasive TKAs during the past
      9 months with early results that indicate less intraoperative blood loss, shorter
      length of stay, increased range of motion (ROM), with similar implant accuracy to
      standard TKA. These new procedures will require thorough evaluation as with any
      new clinical endeavor. It also is of paramount importance to remember that the
      main goal of any new technology is to advance the science of medicine without
      compromising the ultimate result for the patient. The early findings are
      encouraging for the future of minimally invasive TKA and we hope to improve the
      technology during the next few years.

PMID- 14646761
TI  - An oxidized Zr ceramic surfaced femoral component for total knee arthroplasty.
AB  - A ceramic surfaced oxidized Zr femoral component was used in total knee
      replacedent. Prior mechanical testing had shown a decrease in adhesive and
      abrasive wear using this material as compared with CoCrMo suggesting its use in
      younger patients in whom long-term PE wear is a consideration. The alloy had no
      demonstrable Ni impurities and was applicable to patients with Ni or Co
      allergies. In a randomized prospective study comparing femoral components of the
      same design but fabricated either of cast CoCrMo or oxidized Zr, there was a more
      rapid return of flexion and regaining functional milestones in the oxidized Zr
      group. No adverse effects had been observed at the 2-year evaluation.

PMID- 14646762
TI  - The kinematics of fixed- and mobile-bearing total knee arthroplasty.
AB  - The success of any total knee arthroplasty (TKA) is influenced by a complex
      interaction between component geometry and the surrounding soft tissues. The
      objective of this study was to investigate posterior femoral translation and
      tibial rotation in a single design posterior-stabilized TKA offering fixed- and
      mobile-bearing tibial components. Specifically, we examined whether mobile
      bearing TKA restores normal knee translation and rotation better than fixed
      bearing TKA design. Eleven human knee specimens retrieved postmortem were tested
      using a robotic system. The translation and rotation of the intact and
      reconstructed knees were compared. The data indicate that for all knees,
      posterior femoral translation occurs along the passive path and under muscle
      loading conditions. Furthermore, increasing flexion angle corresponded with
      increased internal tibial rotation. Femoral translation and tibial rotation for
      fixed- and mobile-bearing posterior-stabilized TKAs were similar despite
      component design variations. However, both arthroplasties only partially restored
      intact knee translation and rotation. The data presented here may serve as an aid
      in the development of a rationale for additional improvement in surgical
      techniques and prosthesis design, so that normal knee function may be restored.

PMID- 14646763
TI  - Total knee replacement in patients with diabetes mellitus.
AB  - The purpose of the current study was to review the results of total knee
      replacement (TKR) in patients with diabetes mellitus and to test the hypothesis
      that patients with diabetes achieve inferior results after TKR. From a
      consecutive series of 5220 primary cemented TKRs, 363 were done in 291 patients
      with diabetes mellitus. Cefuoxime-impregnated cement was used routinely. The
      results in the study group were compared with the results in the patients without
      diabetes who had TKR during the same period. The followup averaged 52 months.
      Knee scores were higher in patients with diabetes preoperatively (47 versus 38)
      and postoperatively up to 7 years (80 versus 75). The average preoperative and
      postoperative pain scores also were higher in patients with diabetes. Four deep
      infections (1.2%) occurred in patients with diabetes versus 35 deep infections
      (0.7%) in patients without diabetes. The revision rate (including infections) was
      greater in patients with diabetes (3.6% versus 0.4 %). Knee and pain scores were
      similar in patients with insulin-dependent and noninsulin-dependent diabetes.
      Postoperative function scores, however, were lower in patients with insulin
      dependent diabetes. In the study group, all deep infections occurred in patients
      with insulin-dependent diabetes.

PMID- 14646764
TI  - Stem fixation in revision total knee arthroplasty: a comparative analysis.
AB  - Methods of stem fixation are a controversial aspect of revision TKA. We sought to
      determine which technique was superior by reviewing 475 revision TKAs done
      between 1986 and 2000. Of these 475 revisions, 286 major component revisions were
      done using 484 extended stems for fixation. Patients who died, patients who had
      less than 2 years follow up, or patients who had diaphyseal engaging stems were
      excluded from the study. The final data set included 113 revision TKAs with 202
      metaphyseal engaging stems. Of the 202 stems, 107 were cemented whereas 95 were
      press-fit metaphyseal engaging stems. One hundred one of these were femoral stems
      and 101 were tibial stems. Using a modified Knee Society radiographic scoring
      system, 100 (93%) of the 107 implants with cemented stems were considered stable,
      seven (7%) were categorized as possibly loose requiring close followup, and none
      were loose. Of the 95 implants placed with cementless stems, only 67 (71%) were
      categorized as stable. Eighteen (19%) were possibly loose requiring close
      followup and 10 (10%) were loose (two tibial and eight femoral implants). We
      currently would urge caution in using cementless metaphyseal engaging stems for
      fixation in revision TKA.

PMID- 14646765
TI  - Biomechanical evaluation of multidirectional glenohumeral instability and repair.
AB  - The purpose of the current study was to create a multidirectional glenohumeral
      instability model and compare anterior capsulolabral reconstruction with inferior
      capsular shift with respect to their effects on glenohumeral translation and
      rotational range of motion. Ten fresh frozen cadaveric shoulders were used with a
      custom shoulder translation testing jig. To create the multidirectional
      instability model the capsule was stretched an additional 20% from the initial
      rotational range of motion in apprehension and neutral positions. Shoulders were
      repaired using anterior capsulolabral reconstruction (n = 5) or an inferior
      capsular shift (n = 5). Anterior, posterior, inferior, and superior translations
      were measured along with the rotational range of motion for intact, stretched,
      and repaired conditions. All specimens showed increased translations and
      rotations after stretching. Both repair techniques significantly reduced
      anterior, posterior, and inferior translation. The inferior capsular shift was
      more effective in reducing inferior translation in the apprehension position;
      however, postoperative rotational range of motion was restricted significantly
      when compared with anterior capsulolabral reconstruction, and posterior
      subluxation of the humeral head was seen in all specimens. These results indicate
      that a vertical capsulorrhaphy with a medial to lateral shift of the glenohumeral
      capsule, as in the inferior capsular shift repair, significantly reduces
      rotational range of motion when compared in vitro with the horizontal shift of
      the anterior capsulolabral reconstruction.

PMID- 14646766
TI  - Scapulothoracic dissociation: diagnosis and treatment.
AB  - Scapulothoracic dissociation is an important and increasingly common clinical
      condition resulting from massive traction injury to the anterolateral shoulder
      girdle with disruption of scapulothoracic articulation. It frequently is
      accompanied by an acromioclavicular separation, displaced clavicular fracture, or
      sternoclavicular disruption. Vascular lesions have been reported in 88% of
      patients and severe neurologic injuries occur in 94% of patients. Many patients
      have a poor outcome with a flail extremity in 52%, early amputation in 21%, and
      death in 10%. Early recognition of this injury combined with a logical treatment
      protocol can help to decrease the substantial morbidity and mortality associated
      with this condition.

PMID- 14646767
TI  - Morphologic features of congenital acetabular dysplasia: one in six is
      retroverted.
AB  - It generally is thought that in congenital hip dysplasia, the opening of the
      acetabulum lies in excessive anteversion from the sagittal plane. Although this
      is true for the majority of patients, we found that one in six patients with
      acetabular dysplasia has retroversion in which the superior 1/3 of the acetabulum
      faces posterolaterally. Our method of analysis depends mainly on one true
      orthograde view of the pelvis. This view can be obtained easily and has the
      advantage of allowing the surgeon to adjust the correction during surgery. In the
      dysplastic hip with acetabular retroversion, realignment osteotomy still may be
      done but the corrective maneuvers are different.

PMID- 14646768
TI  - Functional outcome after revision hip arthroplasty: a metaanalysis.
AB  - The current study systematically reviews the literature describing patient
      outcomes after revision total hip arthroplasties using conventional global hip
      score ratings. Two thousand one hundred thirty-seven English-language articles
      published from 1966 through 2000 were identified through a computerized
      literature search and bibliography review. A three-step filter process was used
      to identify articles to be included in the metaanalysis. Forty-two articles with
      2578 patients had data abstracted for the analysis. Metaanalysis of global hip
      scores was done using a fixed effects model with the assumption that the
      variances of each measurement were identical across studies. Thirty-nine articles
      reporting on 46 cohorts progressed through three filters and went to data
      extraction and analysis. Revision total hip arthroplasty is a reasonably safe and
      effective procedure for failed hip replacement Based on this exploratory analysis
      revision hip procedures seem to have comparable longevity, to primary hip
      replacement but appear to have slightly lower functional outcome (as measured by
      global hip scores), and slightly higher morbidity and mortality rates than
      primary procedures. Inconsistent reporting in the original studies limited
      exploration of other factors that may have affected outcomes.

PMID- 14646769
TI  - Long-term results of low contact stress mobile-bearing total knee replacements.
AB  - Five hundred ninety-eight consecutive primary low contact stress total knee
      replacements were done in 502 patients between 1985 and 1990. Clinical review was
      available for 495 knees (406 patients), 228 knees with meniscal-bearing
      prostheses and 267 knees with rotating-platform prostheses. The average followup
      was 12 years (range, 10-15 years). The average postoperative knee and functional
      scores were 87 points and 75 points, respectively. The average postoperative
      range of motion was 110 degrees. Fifty-six knees (11%) required revision for
      excessive wear of the tibial insert (41), dislocation (10), patellar polyethylene
      breakage (one), component loosening (one patellar, one tibial), and infection
      (two). During revision, osteolysis (20 knees), patellar polyethylene failure
      (33), and femoral component fracture (one) were seen. The overall survivorship
      was 88.1% at 15 years using Kaplan-Meier analysis. The survival rate was 83% for
      the meniscal-bearing prostheses and 92.1% for the rotating-platform prostheses.
      The Low Contact Stress mobile-bearing knee prosthesis has no superiority over
      that of fixed-bearing knees, especially for the meniscal-bearing design in
      prevention of polyethylene failure or revision. Based on the results of this
      study, the use of the LCS meniscal-bearing prosthesis does not appear to be
      justified.

PMID- 14646770
TI  - Correction of leg-length discrepancy after hip transposition.
AB  - Four patients were treated with limb lengthening to correct a leg-length
      discrepancy that developed after a hip transposition after pelvic resection for
      sacroma of the pelvis. Three patients had Ewing's sacroma and one patient had
      osteosarcoma. All patients received chemotherapy; radiotherapy also was
      administered to the three patients with Ewing's sacroma. Femur lengthening was
      started at an average of 5.7 years (range, 4.4-6.8 years) after tumor surgery. At
      the start of elongation, the average age of the patients was 17.3 years (range,
      10.3-20.8 years). The average leg-length discrepancy was 10.3 cm (range, 6-12
      cm). The average of achieved lengthening was 6.4 cm (range 6-7.5 cm). The average
      healing index was 32 days (range, 27-40 days) per 1-cm elongation. According to
      the classification of Paley, two problems and two minor complications were
      treated by additional interventions. At the final followup, the average
      functional score was 22 (73%) according to the system of the Musculoskeletal
      Tumor Society. Leg-length discrepancy after hip transposition can be corrected
      with distraction osteogenesis. All patients who wore a stiff ankle-foot orthosis
      before lengthening wore an ordinary shoe lift after lengthening. The problems of
      the lengthening procedure are similar to the general complication rate of bone
      lengthening. Because the 5-year survival after resection of a pelvic sarcoma is
      only 20% to 30%, leg lengthening after hip transposition should be offered only
      to long-term survivors with at least 5 years event-free survival.

PMID- 14646771
TI  - Metatarsal giant cell tumors and giant cell reparative granuloma are similar
      entities.
AB  - Light and electron microscopic investigations and studies of the resorption
      ability in vitro of giant cells were done in two patients with giant cell
      osteolytic lesions of metatarsal bone. Giant cells harvested from both patients
      were similar in morphologic features and ability to resorb dentin. After other
      diagnoses of osteolytic lesions of metatarsal bone were ruled out, one lesion was
      considered a giant cell reparative granuloma and the other a true giant cell
      tumor of bone. Clinical, radiologic, ultrastructural, functional studies, and
      data in the literature, indicated that giant cell reparative granuloma only can
      be differentiated from giant cell tumor by younger age at diagnosis and the
      occurrence of giant cell clusters. All other features (cortical erosion, high
      rate of recurrence, hemorrhage areas, predominant intercellular collagenous
      substance) are characteristic of both lesions. If these two giant cell lesions
      are different entities, more accurate means are needed to distinguish them.

PMID- 14646772
TI  - Palmar plating with calcium phosphate bone cement for unstable Colles' fractures.
AB  - A prospective study was done in 20 patients with unstable Colles' fractures with
      metaphyseal bone defects and who were treated with palmar plating combined with
      injectable calcium phosphate bone cement. The patients were three men and 17
      women with a mean age of 69 years (range, 65-86 years) at the time of the injury.
      The followup after the operation ranged from 6 to 24 months (mean, 12 months).
      Union was gained in all the patients. The records of radiographic parameters,
      including the palmar tilting angle, radial inclination, radial length, and ulnar
      variance had been maintained since the surgery. According to the rating scale of
      Gartland and Werley, 16 patients had excellent results and four had good results.
      There were no neurovascular and tendon injuries as complications.

PMID- 14646773
TI  - Combination of local and systemic parathyroid hormone enhances bone regeneration.
AB  - Parathyroid hormone is one of the most promising therapeutic agents for
      osteoporosis, but its use to facilitate bone regeneration in osseous defects is
      less clear. The purpose of the current study was to determine the effects of
      combining systematic parathyroid hormone and a local parathyroid hormone gene
      therapy in a critical-sized osteotomy model. Rats received bilateral femoral
      osteotomies followed by implantation of a gene-activated matrix encoding
      parathyroid hormone (1-34) on one side and a control gene-activated matrix on te
      opposite side. Systematic parathyroid hormone (1-34) or vehicle was injected
      daily and rats were sacrificed 6 weeks later. Systematic parathyroid hormone
      increased bone mineral density and bone mineral content measured by dual-energy
      xray absorptiometry analysis of tibias and vertebrae, and increased serum
      osteocalcin levels during healing of osteotomies. Furthermore, comparing
      osteotomy sites that received the same gene-activated matrices as vehicle
      injected rats, parathyroid hormone-injected rats showed trends of greater bone
      areas via histomorphometric and microradiographic analyses and higher osteocalcin
      messenger ribonucleic acid expression via Northern blot analyses. The combination
      of systemic and local parathyroid hormone led to higher bone mineral density,
      bone mineral content, and bone area, a trend for greater radiographic-detected
      bone area and higher expression of osteocalcin in osteotomy sites when compared
      with the individual treatment or control groups. Local parathyroid hormone gene
      therapy enhanced the anabolic effect of systemic parathyroid hormone during
      osteotomy healing. This study supports the concept of a combined local and
      systemic approach for enhancing the repair of a fracture at risk for nonunion.

PMID- 14646774
TI  - Left calf mass in a 13-year-old boy.

PMID- 14646775
TI  - Proximal tibial pain and mass in a 13-year-old girl.

PMID- 14646776
TI  - Hip pain in a 12-year-old boy.

PMID- 14646778
TI  - Defining advanced practice nursing.

PMID- 14646779
TI  - Practical and professional tidbits for case management and physician team
      building.

PMID- 14646780
TI  - Effective reporting of case management outcomes: justifying your department's
      existence.

PMID- 14646781
TI  - Using a case management model to implement a faith-based initiative: addressing
      breast cancer in a rural African American population.

PMID- 14646782
TI  - Fall prevention in frail elderly nursing home residents: a challenge to case
      management: part I.
AB  - Parts I and II of this article examine the impact of a falls prevention program
      on the fall incidents among the residents in a nursing home. It was hypothesized
      that a diagnostic, therapeutic, and preventive approach should be used for
      nursing home residents identified as being at high risk for falls in order to
      reduce the number of fall incidents and to improve quality of life for this
      vulnerable population. The program effectively targeted both intrinsic and
      extrinsic factors to reduce risks facing the residents. The effectiveness of the
      program was evaluated by examining changes in the rate of falls after the program
      was implemented. The results identified that a multifaceted program, one that
      utilized multiple personalized interventions, was effective in reducing the falls
      rate of frail (those with complex medical and psychosocial problems) nursing home
      residents, and that muscle-strengthening interventions may be beneficial for this
      vulnerable population. Program outcomes verified that case managers can impact
      quality of life for frail elderly nursing home residents by promoting their
      independence and safety, and postponing problems resulting from inactivity. Part
      I discusses the background and process of a falls program and factors
      contributing to the occurrence of falls. Part II will examine the
      interdisciplinary team approach to assessment, method, and implementing
      strategies for an effective fall prevention program. Tools used for prevention,
      monitoring, and investigation of falls will be detailed in Part II.

PMID- 14646783
TI  - Operating a sustainable disease management program for chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of our nation's
      most rapidly growing chronic health conditions. It is estimated that over 16
      million individuals are diagnosed with COPD (Friedman & Hilleman, 2001). In
      addition, another 16 million are misdiagnosed as asthma or not diagnosed at all.
      COPD is a condition that affects the working-age as well as the elderly. Despite
      the high mortality rate, COPD is a treatable and modifiable condition. Disease
      management programs (DMPs) for asthma are a common initiative within many health
      insurance plans and integrated delivery networks. Similar initiatives are not as
      common for COPD. This article will highlight the National Jewish Medical and
      Research Center's COPD DMP interventions and outcomes. OBJECTIVE: To outline
      interventions and operational strategies critical in developing and operating a
      sustainable and effective disease management program for COPD. CONCLUSIONS:
      Disease Management is an effective model for managing individuals with COPD.
      Applying a case management model that includes (1) risk-identification and
      stratification; (2) education and empowerment regarding self-monitoring and
      management; (3) lifestyle modification; (4) communication and collaboration
      amongst patients, healthcare providers, and case managers to enhance the
      treatment plan; (5) providing after-hours support; and (6) monitoring care
      outcomes is crucial. Applying these interventions in a credible manner will
      improve the quality of life and quality of care delivered to individuals with
      mild, moderate, severe, and very severe COPD. Additionally, these interventions
      can significantly reduce utilization events.

PMID- 14646784
TI  - A disease management program for heart failure: collaboration between a home care
      agency and a care management organization.
AB  - This article describes a collaborative approach to manage patients with heart
      failure between a home care agency and a care management agency. The resulting
      disease management program used a combination of home visits and phone contact.
      Care management plans emphasized patient education on increasing adherence to
      medical and diet regimens, and recognizing early symptoms of exacerbation that
      could lead to rehospitalization. Clinician activities and patient outcomes are
      described.

PMID- 14646785
TI  - A short social support measure for patients recovering from myocardial
      infarction: the ENRICHD Social Support Inventory.

PMID- 14646786
TI  - Aspects of social support associated with depression at hospitalization and
      follow-up assessment among cardiac patients.
AB  - PURPOSE: High levels of depressive symptoms have been shown to affect the
      morbidity, mortality, and functioning of patients with myocardial infarction
      (MI). Findings have shown that social support is associated with depression in
      both patient and community samples. This study examined various aspects of social
      support as they relate to depressive symptoms in patients with MI, both in the
      hospital and 2 weeks later. METHODS: As part of the Enhancing Recovery in
      Coronary Heart Disease (ENRICHD) pilot study, measures of perceived social
      support, social networks, social support received, and social conflict were
      administered to 196 patients with MI. These patients also were administered the
      Beck Depression Inventory and the Hamilton Rating Scale for Depression.
      Depression was reassessed 2 weeks later. Relations between social support
      indicators and the depression measures were examined. RESULTS: The prevalence of
      depression symptoms was high, especially among poorer and younger patients. There
      was modest improvement across time. Patients with high social support scores,
      particularly those reflecting perceived support, had lower scores on depression
      measures at baseline. High levels of perceived support and low social conflict at
      baseline were associated with less follow-up depression, as measured by the Beck
      cognitive scale, but not the Beck somatic scale nor the Hamilton scale. There
      were few associations with measures of social networks and received support.
      CONCLUSIONS: Social support indicators were differentially related to depression
      among patients with MI while in the hospital and 2 weeks later. The pattern of
      associations also depended on the measure of depression. A broad assessment
      strategy of both social support and depression is needed for a full understanding
      of their interrelations.

PMID- 14646787
TI  - Social support for patients after myocardial infarction.

PMID- 14646788
TI  - Long-term behavioral outcomes after attendance at a secondary prevention clinic
      for cardiac patients.
AB  - PURPOSE: Secondary prevention interventions, including hospital clinics, can help
      patients improve their risk factors and lifestyles after an acute cardiac event.
      This study aimed to investigate the long-term behavioral outcomes of attending
      and nonattending patients consecutively enrolled in a trial of a family-based
      clinic providing screening, advice, and support 3 months after hospital
      admission. The study also aimed to identify predictors of long-term smoking
      status, dietary habit, and physical activity. METHODS: Semistructured interviews
      were conducted an average of 30 months after the acute cardiac event with 83 of
      the 103 nonattending patients and a random sample of 96 patients who had attended
      the clinic. Behavioral outcomes were investigated, and self-reported risk factors
      at the time of the acute illness were documented. RESULTS: The patients who had
      attended the clinic were significantly more likely than nonattenders to report
      positive dietary changes and, among former smokers, successful cessation of
      smoking. Furthermore, they reported being more physically active than
      nonattenders. Using logistic regression, clinic attendance was identified as a
      significant and independent predictor of all three outcomes. CONCLUSIONS: The
      results of this observational study suggest that attendance at a secondary
      prevention clinic facilitates maintenance of improved long-term health behaviors,
      although this finding is based on self-report. Factors possibly responsible for
      favorable outcomes include strong physician advice and support from a
      multidisciplinary team of health professionals. Furthermore, the timing of the
      intervention may have been appropriate for enrollment in a secondary prevention
      clinic.

PMID- 14646789
TI  - Measuring improvements in preventive cardiology outcomes: the bumpy road between
      theory and practice.

PMID- 14646790
TI  - Quality patient care in a successful business model.

PMID- 14646791
TI  - A new unsupported upper limb exercise test for patients with chronic obstructive
      pulmonary disease.
AB  - PURPOSE This study aimed to develop a new unsupported upper limb exercise test
      (UULEX) for patients with chronic obstructive pulmonary disease (COPD). METHODS:
      The reproducibility of the UULEX was assessed in nine patients with COPD who
      performed the test on three occasions. A comparison of the UULEX and a supported
      incremental upper limb exercise test (SULEX) using an arm ergometer also was
      performed with 18 patients who had COPD. RESULTS: There were no significant
      differences in the maximum values for each cardiorespiratory variable and
      sensation of dyspnea between the three repetitions of the UULEX, and all the
      variables showed high reproducibility. During the supported test, maximum values
      for the cardiorespiratory variables were significantly higher, but the ratio of
      minute ventilation to carbon dioxide output was lower than during the unsupported
      exercise test. There were significant correlations for cardiorespiratory
      responses, arm muscle fatigue, and sensation of dyspnea between the two tests.
      CONCLUSIONS: The findings suggest that the new UULEX test is a reproducible and
      acceptable exercise test for patients with COPD that can be used as a simple
      method to evaluate upper limb function in these patients. Further studies are
      required to determine the external validity of the test and its sensitivity to
      interventions such as pulmonary rehabilitation.

PMID- 14646792
TI  - Psychometric properties of four QOL instruments.

PMID- 14646793
TI  - [The ultradian rhythm of sleep: diverse relations with pituitary and adrenal
      hormones].
AB  - We evaluated the relationship between the ultradian rhythm of sleep and the
      secretory episodes of pituitary-adrenal hormones. Prolactin (PRL) and TSH
      exhibited opposite phase relationships with delta waves, PRL increasing and TSH
      decreasing when delta waves developed. Delta waves never increased together with
      an increase in cortisol secretion. They oscillated independently from each other
      throughout the 24 hour period, but when they were present at the same time, they
      oscillated in opposing phases. Concerning growth hormone (GH), its major peak
      which occurred shortly after sleep onset in association with the first slow wave
      sleep episode was blunted during sleep deprivation. However, this blunting was
      compensated during the day, so that the amount of GH secreted during a 24-hr
      period was similar whether or not a person had slept during the night. The
      physiological significance and the clinical implications of the various
      relationships of the endocrine systems with sleep are poorly known.

PMID- 14646794
TI  - [Impact of sleep debt on physiological rhythms].
AB  - Sleep loss due to voluntary bedtime curtailment has become a hallmark of modern
      society. Even though sleep deprivation in rodents has been shown to result in
      death, it was until a few years ago thought that sleep loss results in increased
      sleepiness and decreased cognitive performance but has little or no adverse
      effects on human health. We measured sleep and 24-hour hormonal profiles in 11
      healthy young males after 6 days of sleep restriction (4-hour bedtime) and after
      6 days of sleep recovery (12-hour bedtime). At the end of sleep restriction, we
      observed reduced amounts of slow wave sleep (SWS) and rapid eye movement (REM)
      sleep and an alteration in the temporal distribution of these sleep stages, i.e.
      an increased pressure for REM sleep at the beginning of the sleep period and a
      decrease in the amount of slow wave activity (SWA) during the first sleep cycle.
      These later abnormalities are usually observed in depression. In addition,
      numerous alterations in the 24-hour hormonal profiles were observed in the state
      of sleep debt. The amount of melatonin secreted was reduced because of a delay in
      the onset of the nocturnal secretion and a reduction in the value of the
      acrophase. If the overall 24-hour cortisol profile was preserved, sleep
      restriction was associated with increased cortisol levels in late afternoon and
      evening hours and the duration of the quiescent period was reduced. The 24-hour
      mean TSH levels were reduced and the nocturnal TSH elevation was markedly
      dampened, most likely as a result of elevated levels of thyroid hormones. The
      acrophase of the 24-hour leptin profile occurred earlier, the amplitude of the
      rhythm and the overall mean levels were reduced. The nocturnal elevation of
      prolactin levels was abrupt but of short duration and the 24-hour mean levels
      were decreased. A pulse of growth hormone occurred prior to sleep onset,
      therefore affecting SWA distribution at the beginning of the sleep period. Since
      these alterations are qualitatively and quantitatively similar to those observed
      during aging and sometimes during depression, a state of sleep debt, as is
      experienced by a substantial fragment of the population in modern societies, is
      likely to increase the severity of depression and widespread age-related chronic
      conditions such as obesity, diabetes and hypertension.

PMID- 14646795
TI  - [Inversion of the circadian melatonin rhythm in Smith-Magenis syndrome].
AB  - Smith-Magenis syndrome (SMS) is a genetic disease ascribed to an interstitial
      deletion on chromosome 17 (del 17p11); the prevalence is 1/25,000 births. The
      diagnosis is made on high-resolution karyotype confirmed by FISH. Clinical
      features include mild dysmorphism, short stature, other malformations (heart,
      renal, neurologic diseases). Mental retardation is constant; there are major
      behavioral disturbances and severe sleep disorders. We studied sleep disorders
      and melatonin secretion in SMS children and we have shown inversion of the
      circadian rhythm of melatonin, abnormally secreted during the day. This is the
      first biological model of behavioral and sleep disorder in a genetic disease.
      Therapeutic approach using beta-blockers in the morning and melatonin in the
      evening, reset circadian rhythm of melatonin, improve behavior and restore sleep.

PMID- 14646796
TI  - Memory processing during human sleep as assessed by functional neuroimaging.
AB  - Sleep is believed to participate in memory consolidation, possibly through off
      line processing of recent memory traces. In this paper, we summarize functional
      neuroimaging data testing this hypothesis. First, sleep deprivation disrupts the
      processing of recent memory traces and hampers the changes in functional
      segregation and connectivity which underpin the gain in performance usually
      observed in subjects allowed to sleep on the first post-training night. Second,
      experience-dependent changes in regional brain activity occur during post
      training sleep. These changes are shown to be related to the processing of high
      level material and to be modulated by the amount of learning achieved during the
      training session. These changes do not involve isolated brain areas but entire
      macroscopic cerebral networks. These data suggest a role for sleep in the
      processing of recent memory traces.

PMID- 14646797
TI  - [Thermal regulation during sleep].
AB  - Many studies point out that ambient temperatures outside the thermoneutral zone
      disturb sleep. Thermal responses depend on the phase of sleep and it appears that
      rapid eye movement (REM) sleep and thermoregulation are mutually exclusive in
      animals. In humans, there is evidence that this thermoregulatory disruption is
      less important since the thermal responses to heat or cold exposures are not
      abolished. Thermal responses persist during slow wave sleep (SWS). These
      differences suggest that there is a hierarchical control of body temperature
      regulation. The control includes different integrators at many levels of the
      nervous system with each level facilitated or inhibited by levels above and
      below. During SWS, body temperature is controlled by diencephalic structures
      whereas during REM sleep there is a suspension of hypothalamic thermoregulatory
      influences. The thermoregulatory differences may be accounted for by the neural
      organization and the autonomy of brain stem and spinal operative levels which
      differ between sleep phases and species. However, in the neonate,
      thermoregulation is not impaired during active sleep (AS) and Quiet Sleep (QS)
      considered, from behavioral and polygraphic measures, as immature forms of REM
      and SWS, respectively. From a thermoregulatory point of view, AS seems to be a
      well-protected sleep phase. As regards the thermal responses, these observations
      suggest that neonatal active sleep may be a precursor both of REM sleep and SWS
      in adults.

PMID- 14646799
TI  - [Effect of the first sleep night in polysomnography: classification by variable
      sensitivity and factorial analysis of differences between nights].
AB  - It has been known since the sixties that a habituation phenomenon is present in
      polysomnographic analyses of sleep, the first night including more awakenings and
      less Rapid Eye Movement sleep (REM) than consecutive ones. Results about Non
      Rapid Eye Movement sleep (NREM) are less clear. The study presented here
      attempted to classify the variables in function of their sensitivity to this
      phenomenon by comparing inter-night and inter-subject effects in a series of
      ANCOVA analyses and on the other hand, to group the same variables in function of
      a factorial analysis on the differences between the two first nights. The study
      included 26 subjects with no somatic nor psychiatric disorder and was performed
      at their homes for four consecutive nights. The most sensitive variables were, in
      descending order: Ultra-Slow spectral power band, REM sleep, Sleep Efficiency
      Index, Delta spectral power band, number of awakenings, duration of awakenings,
      number of ultradian sleep cycles and Total Sleep Time. The factorial analysis
      showed 7 factors, grouping separately the two series of results from the spectral
      analysis (corresponding to visually-scored NREM and REM sleep), awakenings, sleep
      duration variables, variables linked to REM sleep, microarousals and deep sleep.

PMID- 14646798
TI  - [Hypocretins/orexins and narcolepsy: from molecules to disease].
AB  - In order to foresee a curative treatment for narcolepsy, it is crucial to
      determine whether or not human narcolepsy is a neurodegenerative disorder, as we
      suggested, and to understand the mechanisms involved. The current hypothesis
      regarding the etiology of human narcolepsy is that it is an autoimmune disorder,
      because of its strong association with the human leukocyte antigen (HLA
      DQB1*0602), with the Hcrt neurons as the target. This hypothesis is supported by
      our results (Peyron et al., 2000) and others (Thannickal et al., 2000) showing
      that Hcrt messengers RNA and mature peptides are absent or greatly reduced in the
      brain of HLA DQB1*0602 positive narcoleptic patients examined to date. It is of
      great importance to determine whether the absence of Hcrt is due to a
      neurodegenerative process or to a default in the transcription process. After a
      brief review on hypocretins and narcolepsy, we discuss on how to tackle the
      issue.

PMID- 14646800
TI  - [Development of compounds active in insomnia: recent developments and
      methodological aspects].
AB  - Most pharmacotherapeutic treatments designed to treat insomnia target GABAergic
      activity globally in the brain. Development of new molecules having a more
      specific activity pathway should improve treatment efficacy and acceptance. Both
      subjective and objective criteria are needed to study drug efficacy. Data
      regarding drug effects on polysomnographic recordings are mandatory for the
      development of hypnotics. Whether the drug-induced sleep is comparable to normal
      sleep is tackled with the spectral analysis of the sleep EEG. Residual drug
      effects are assessed with a package of psychomotor and neurocognitive tests, and
      with the driving simulator test Clinical studies investigating drug efficacy and
      tolerability have to be conducted on large groups of patients carefully selected
      using polysomnographic recordings. Our knowledge about sleep will undoubtedly
      soon become available for treatment of insomnia.

PMID- 14646801
TI  - [Introduction. Neurodegenerative diseases and sleep].

PMID- 14646802
TI  - [Neuropathology of tauopathies and synucleinopathies, and neuroanatomy of sleep
      disorders: meeting the challenge].
AB  - Abnormalities of tau and alpha-synuclein have been described in a variety of
      neurodegenerative diseases often associated with sleep disorders.
      Neuropathological descriptions concerning these diseases are rapidly expanding,
      and they become difficult to summarise. On the other hand, the human neuroanatomy
      of sleep remains an ill defined issue. Main tauopathies are Alzheimer's disease,
      progressive supranuclear palsy, cortico-basal degeneration, argyrophilic grain
      disease, Pick disease and fronto-temporal degeneration with Parkinsonism
      associated with chromosome 17. In contrast to Alzheimer's disease, where abnormal
      tau containing cells are mainly neurones, in the other disorders, both neurones
      and glial cells are affected. The presynaptic protein alpha-synuclein is a major
      constituent of Lewy-type lesions in Parkinson disease and in dementia with Lewy
      bodies. Alpha-synuclein is also found in neurones and glia of Multi System
      Atrophy. This led to group these disorders into the still ill defined group of
      synucleinopathies. The lesions of tauopathies and synucleinopathies are
      presented, and their distribution in the most common disorders is described,
      distinguishing when possible neuronal loss and neuropathological markers. Recent
      data show that their extension is far larger than previously assumed and that
      they involve a variety of areas possibly involved in sleep regulation. Sleep
      disorders have been described in various tauopathies and synucleinopathies.
      However, no detailed clinico-pathological reports concerning the distribution of
      affected and spared areas in patients studied by polysomnography are available.
      Furthermore, the similarities of sleep disorders associated with different
      diseases, the interindividual variability, the frequently associated disorders,
      and the difficulties in quantifying neuronal loss make any clinicopathological
      correlation uncertain. The knowledge of sleep neuroanatomy is mainly based on
      animal studies. The few data concerning the structures of human brain areas
      involved in sleep organisation are recalled. Several systems known to be acting
      in sleep physiology are usually affected by tauopathies and synucleinopathies,
      but the pattern of their involvement in sleep pathology remains highly
      conjectural. The neuropathology of sleep disorders in tauopathies and
      synucleinopathies is a still uncultivated field.

PMID- 14646803
TI  - [Wakefulness and central basal nuclei: experimental observations and possible
      implications in Parkinson's disease].
AB  - Movement disorders in Parkinson disease, notably dampened during sleep, are
      associated with hyperactivity of the subthalamic nucleus (STN), whose origin is
      controversial. We have studied, on non-anaesthetized head-restrained rats, the
      STN spontaneous unit activity and the one of its principal GABAergic afferents,
      the globus pallidus (GP). In normal rats, STN neurons shifted from a random
      discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS),
      without any change in their mean firing rate. In contrast GP neurons, with a mean
      firing rate higher in W than in SWS, exhibited a relatively regular discharge
      rate whatever the vigilance state. During paradoxical sleep, both STN and GP
      neurons increased markedly their firing rate. When applied during W, GABA-A
      antagonists increased the STN firing rate but did not change the typical W random
      pattern. When applied during SWS, they strongly reinforced the spontaneous burst
      pattern into a particularly marked one with instantaneous frequencies reaching
      500Hz. SWS-W transitions occurring during ongoing antagonist iontophoresis
      invariably disrupted this burst pattern into a random one. On 6-OHDA unilaterally
      treated rats, the ipsilateral STN was hyperactive whatever the vigilance state
      (with an abnormal burst pattern during W on some neurons), but this hyperactivity
      did not seem to be associated with a GP hypoactivity. These results show that STN
      activity is not inversely correlated with GP activity, that its discharge pattern
      is strongly dependent on vigilance states, that GABA receptors do not play an
      exclusive role in regulating its firing pattern, and question the depolarization
      block hypothesis during STN high frequency stimulation.

PMID- 14646804
TI  - [Sleep disorders during synucleopathies and taupathies].
AB  - Dissociate states of rapid eye movement sleep (REM) are much more frequent in
      patients with synucleopathy than in patients with taupathy (except that REM sleep
      behavior disorder may affect one third of patients with supranuclear palsy), as
      are sleep onset REM periods, observed in patients with Parkinson's disease,
      multiple systemic atrophy and Lewy body disease. Recent evidences suggest that
      they may result from non dopaminergic lesions, including cholinergic neurons in
      the locus subcoeruleus and orexinergic neurons in the lateral hypothalamus.

PMID- 14646805
TI  - [Neurodegenerative, autoimmune and genetic processes of human and animal
      narcolepsy].
AB  - Narcolepsy is a rare disabling sleep disorder whose main features are excessive
      daytime sleepiness and cataplexy. Human narcolepsy is most frequently a sporadic
      disorder with both genetic and environmental factors playing a role in its
      pathophysiology. Implication of the hypocretin system is well-established: as
      mutations in both canine and murine narcolepsies and as a consistent reduction in
      hypocretin neuron in human narcolepsy. The cause of human narcolepsy remains
      unknown. However degenerative, autoimmune and/or genetic processes are the most
      probable causes of the hypocretin neurons loss. Acting on a specific genetic
      background, an autoimmune process with hypocretin neuron degeneration, in
      response to environmental factors, is the most probable hypothesis for most cases
      of human narcolepsy with cataplexy. Although narcolepsy presents one of the
      tightest association with a specific HLA antigen (DQB1*0602), there is strong
      evidence that non-HLA genes also confer susceptibility. Monoaminergic, immune
      (TNF alpha) and hypocretinergic systems seem to be involved and may interfere
      with the phenotype. Treatment has not evolved significantly over the last few
      years. However, new drugs, such as hypocretin agonists, are currently being
      developed.

PMID- 14646806
TI  - [Epidemiological definition of obstructive sleep apnea syndrome].
AB  - Obstructive sleep apnea syndrome (OSAS) is currently a clinically defined
      syndrome associating somnolence and on or two of the following symptoms: severe
      snoring, nocturnal respiratory arrest, repeated nocturnal awakening, non
      recuperative sleep, diurnal fatigue, and altered concentration. The
      polysomnographic criterion is a more than 5 apnea-hypopnea episodes plus micro
      awakenings related to respiratory efforts per hour of sleep. The epidemiological
      definition of OSAS is different because the prevalence of OSAS is estimated from
      the prevalence of the apnea-hyponea index (AHI) per hour of sleep and the
      prevalence of somnolence in the population. Epidemiological studies have produced
      different estimates of the prevalence of OSAS. The differences are less
      pronounced but still persist when comparing studies with a similar methodology,
      an identical sample, and sleep laboratory polysomnography recordings. These
      differences are related to the populations studied and also to the recording
      methods with different sensitivity and specificity. The difference between the
      prevalence P, which is the ratio between the number of patients in the study
      population, and the number Q, which is the ratio of the number of positive tests
      in the population, depends on the sensitivity and the specificity of the test
      used. The prevalence is also equal to the number of positive tests only if the
      sensitivity and specificity are both 1. The most widely used method, the
      thermistance method, has poor sensitivity and specificity. Prevalence is probably
      underestimated with this test. A rigorous consensual definition of this OSAS and
      abnormal ventilatory events as well as standardized diagnostic tests adapted for
      epidemiology studies are indispensable.

PMID- 14646807
TI  - [Respiratory disorders during sleep in the pregnant woman].
AB  - Sleep disordered breathing can occur during pregnancy due to the development of
      hormonal changes and respiratory function abnormalities that perturb patency of
      the upper airways. Habitual snoring has been described in 25 p. 100 of the women
      during the third trimester of pregnancy. The incidence of sleep apnea hypopnea
      syndrome is unknown due to the lack of longitudinal epidemiological data, and
      results of the main studies are in favor of upper airway resistance syndrome.
      However, these sleep-related breathing disorders are more frequently associated
      with maternal and fetal complications such as maternal hypertension, pre
      eclampsia and intrauterine growth restriction. This article points out the
      importance of such associations because of the efficacy of continuous positive
      airway pressure on the regression of these nocturnal respiratory and vascular
      complications.

PMID- 14646808
TI  - [Mortality in treated sleep apnea syndrome].
AB  - Obstructive sleep apnea is common and considered to be a risk factor for
      hypertension, stroke and coronary disease. Accordingly, the presence of sleep
      apnea is probably a predictor of premature death. Continuous positive airway
      pressure is an effective treatment of obstructive sleep apnea. It has been
      demonstrated that such treatment improves daytime sleepiness and quality-of-life.
      To determine mortality in obstructive sleep apnea patients treated with nasal
      continuous positive airway pressure, we followed 296 patients given continuous
      positive airway pressure for 11 years 6 months. At the end of the study 26 of the
      296 patients had died, mainly from cardiovascular disease. Mortality was 7% (95%
      confidence interval: 3%-9%) at 5 years. Three independent factors of death
      identified by forward stepwise selection were included in a Cox analysis. These
      factors were 1) smoking as a categorical covariate (>30 pack-years), 2) age and
      3) forced expiratory volume in 1 s. When the 52 patients with an associated
      chronic obstructive pulmonary disease (forced expiratory volume in 1 s/vital
      capacity<0.65) with obstructive sleep apnea were excluded form analysis,
      mortality of the 244 remailing patients was 2% at 5 years, a rate observed in the
      general population. Subsequently, it appears that nasal continuous positive
      airway pressure corrects for the risk of premature death suspected in obstructive
      sleep apnea patients. Mortality in obstructive sleep apnea patients treated with
      continuous positive airway pressure is near to that of the general population,
      particularly when patients with an associated chronic respiratory disease are
      excluded.

PMID- 14646809
TI  - [Obstructive sleep apnea syndrome and genetics].
AB  - The obstructive apnea syndrome (OSA) is considered as a complex genetic disorder.
      Descriptive studies from several countries have consistently show familial
      aggregation of the apnea-hypopnea index and symptoms of OSA in both adults and
      children. Phenotypic markers of OSA have been identifies such as upper airway
      anomalies, abnormal breathing control, and obesity through which genes might act
      to increase susceptibility to OSA. The genetics of OSA may differ among racial
      groups. Two approaches have recently been used to investigate the genetics of
      OSA: a segregation analysis and a whole genome scan. Data suggested a common
      causal pathway regulating both OSA and obesity in Caucasian families.

PMID- 14646810
TI  - [Effect of sleep apnea syndrome on the vascular endothelium].
AB  - Obstructive sleep apnoea (OSA) is a common disorder associated with an increased
      risk of cardiovascular disease and stroke. As it is strongly associated with
      known cardiovascular risk factors, including obesity, insulin resistance, and
      dyslipidemia, OSA is an independent risk factor for hypertension. Although the
      association between OSA and the metabolic syndrome tends to confound studies of
      the independent effects of OSA on vascular disease, recent evidences from basic
      science to epidemiological and clinical studies suggest that OSA may add
      worsening pathophysiological conditions to obesity. OSA contributes to the
      imbalance between vasodilators and vasoconstrictors, in particular through
      oxidative stress-dependent catabolism of nitric oxide, increased sympathetic
      nerve activity, enhanced renin-angiotensin system activity and endothelin
      synthesis. Additionally, several recent studies suggest that OSA may be a
      circumstance favouring central and vascular resistance to leptin. The beneficial
      effects of this hormone in normal subjects, are lost during endothelial
      dysfunction and OSA. Moreover, high leptin concentrations, within a range
      observed during OSA, display adverse effects on endothelial function and vascular
      physiology. Through of a yet unknown mechanism, OSA per se accounts for part of
      the elevated serum leptin concentration reported in patients. The current
      standard treatment for OSA-nasal continuous positive airway pressure (CPAP)
      eliminates apnoea and the ensuing acute hemodynamic changes during sleep.
      Accordingly, vasopressor mediators and leptin concentration are shifted toward
      normal values by CPAP. Thus, in addition to this effective therapy, evaluation of
      specific strategies targeting leptin sensitivity and vasopressor mediators may
      open novel perspectives for treatment of OSA and its associated end-organ
      damages.

PMID- 14646811
TI  - [Cortical arousal, autonomic arousal. Evaluation techniques and clinical
      importance].
AB  - The respiratory disorders expressed by obstructive hypopneas and apneas during
      sleep, as well as the sequences of crescendo in respiratory effort without
      hypopneas or apneas which define the upper airway resistance syndrome, terminate
      with (thanks to) an arousal, defined by EEG changes. In some cases, the
      activation of the central nervous system is restricted to a sympathetic
      activation, which has been mainly studied in the cardiovascular area, and is not
      always accompanied by a cortical arousal. Various approaches (heart rate, blood
      pressure, pulse transit time, peripheral arterial tonometry) make the
      identification of sympathetic activation possible. Sympathetic activation seems
      to be more sensitive than cortical arousal to the stimulations generated by the
      respiratory system via an activation of mechanoreceptors stimulated by the
      increased respiratory effort in response to total or partial occlusion of the
      upper airway. The mechanisms of the cortical or autonomic arousal are not fully
      understood, but their detection could be a diagnostic tool for the identification
      of such disorders. Such tools are currently under validation.

PMID- 14646812
TI  - [Embryology applied to neurosurgery. Introduction to part II].

PMID- 14646813
TI  - [Neurosurgical embryology. Part 5: Temporal landmarks of the development of the
      central nervous system in humans].
AB  - The establishment of temporal landmarks of the development of the central nervous
      system was the primary goal of early human embryologists. The description of
      these landmarks has lost much of its interest since it is now largely accepted
      that the temporal profile of development is at best a poor indicator of the
      origin of malformative syndromes. However, we propose here a rapid review
      describing the principal data available. One of our goals is to present here the
      original data that are needed to understand the morphological aspect of the
      development of the central nervous system. The most important results are the
      presence of a developmental gradient within each anatomical area. This means that
      all the neurons of a specific anatomical region are not generated at the same
      time. There is also another gradient that could be described. This gradient is
      the rostro-caudal gradient: the spinal cord develops first, then the brain stem,
      and finally the encephalon. This rule is only a general rule with many exceptions
      like, for instance, the cerebellum that is a late derivative of the neural tube.

PMID- 14646814
TI  - [Neurosurgical embryology. Part 6: The principal models that can be used in
      developmental biology].
AB  - To study the mechanisms controlling embryonic development, experimental analyses
      must be performed on animal models. There are different species that are
      currently used as models in developmental biology. In invertebrates, drosophila
      remains a very useful model thanks to its rapid development and to the extensive
      study of genes involved in the control of its development. C. elegans has been
      extensively used because of its simplicity due to the total restricted number of
      adult cells in this species. In vertebrates, amphibians remain a very useful
      model with the extensive analysis of Xenopus laevis. The zebrafish is now a
      widely used model because of its genetic analysis. Birds are still used for the
      accessibility of their embryo allowing experimental procedures to be performed in
      ovo. The mouse is now very widely used because it is possible to obtain
      transgenic mice to study both loss or gain of gene function.

PMID- 14646815
TI  - [Neurosurgical embryology. Part 7: Development of the spinal cord, the spine and
      the posterior fossa].
AB  - The spinal cord arises from the most caudal domain of the neural tube whereas the
      vertebrae develop from the para-axial mesoderm (namely the somites). The
      development of the spinal cord and the vertebrae is so intimately linked that it
      is more convenient to present it in the same chapter. The neural tube is formed
      from the neural plate during neurulation. This tube is submitted to a double
      gradient of diffusible molecules that lead to the ventro-dorsal polarization of
      the tube. This polarization is figured as the emergence of sub-domains that
      contain progenitors engaged in a specific lineage. Axial organs induce the
      dissociation of the somites, giving rise to the dermatome, myotome and
      sclerotome. Vertebrae derive from the sclerotome after the so-called
      resegmentation of the somites. During this process, a caudal hemi-somite is
      associated with the rostral hemi-somite of the next caudal somite to
      differentiate into the vertebra. The occipital bone forms the major part of the
      walls of the posterior fossa. This bone develops from the para-axial mesoderm for
      its sub-tentorial part whereas its sus-tentorial derives from neural crest cells.

PMID- 14646816
TI  - [Neurosurgical embryology. Part 8: Post-natal angiogenesis and remodeling].
AB  - Post-natal angiogenesis (microvascular proliferation) and remodeling
      (modifications of diameter and wall thickness) occur in various physiological
      circumstances including adaptation to exercise or wound healing. The formation of
      a new vessel is submitted to the combinative action of growth factors. New
      endothelial cells migrate, proliferate, differentiate and attract pericytes and
      future smooth muscle cells to create the new vessel. Powerful stimuli leading to
      remodeling and to the creation of new vessels are mainly represented by
      hemodynamic forces generated by pressure and blood flow, and by hypoxia. Our
      purpose is to overview the molecular mechanisms and the stimuli giving rise to
      these processes.

PMID- 14646817
TI  - [Transarticular atlanto-axial screw fixation for treatment of C1-C2 instability].
AB  - Posterior transarticular screw fixation of the C1-C2 complex has become an
      accepted method of arthrodesis for patients requiring posterior C1-C2 fusion.
      Since 2000, four patients (2 males and 2 females) were treated with this surgical
      approach for management of atlantoaxial instability, including odontoid fracture
      with unilateral C1-C2 luxation, odontoid pseudarthrosis, complex congenital
      malformation of the craniovertebral junction and rheumatoid arthritis. All
      patients underwent stabilization with 2 transarticular C1-C2 screws, without any
      posterior interspinous graft. Patients were maintained in a rigid cervical
      orthesis 3 months postoperatively. Results were good, without any complication,
      after a short mean follow-up (8 months). Technical aspects of the technique are
      reported, The risk of screw malpositioning and vertebral artery or neural injury
      is minimal and can be lowered by using preoperative CT scan and MRI, and by using
      intraoperative fluoroscopy. Transarticular C1-C2 screw fixation proves to be a
      major surgical approach for treatment of atlantoaxial instability.

PMID- 14646818
TI  - [Microsurgical vascular decompression for hemifacial spasm. Follow-up over one
      year, clinical results and prognostic factors. Study of a series of 100 cases].
AB  - BACKGROUND AND PURPOSE: The results of a series of 100 patients operated on for
      hemifacial spasm (HFS), using microsurgical vascular decompression (MVD), are
      reported. METHOD: MVD was performed through a retromastoid keyhole approach,
      under monitoring of brainstem auditory evoked potentials (BAEP) and facial EMG,
      and consisted in dissection of VII nerve from conflicting vessel(s), and
      interposition of Teflon fibers and/or screen(s). RESULTS: The offending vessels
      found were: the antero-inferior cerebellar artery in 57 cases, the postero
      inferior cerebellar artery in 56 cases, the vertebrobasilar artery in 22 cases. A
      multiple conflict was found in 32 cases (32%). The result was considered
      excellent if there was no residual spasm, good if only "minimal twitching"
      remained with relief>80%, poor for spasm relief 20 to 80%, and as a failure if
      relief<20%. The effect of MVD was satisfying (excellent or good) in 75 patients
      (75%) at discharge (10th day) and in 85 (85%) after 1 to 18 years follow-up
      (mean: 5 years). Amongst the latter patients, 29 (34%) experienced a delayed (up
      to 3(1/2) years in one) cure. Spasm recurrence was noted in 9 cases after
      satisfying effect on discharge. We encountered following permanent neurological
      complications: 1 facial palsy, 7 cases of hearing deficit (5 of them complete),
      and 1 case of IX-X deficit. Neither death nor ischaemic complication at brainstem
      or cerebellum. Most of our hearing complications occurred before using
      intraoperative BAEP monitoring (3 cases of cophosis among our first 7 patients vs
      2 out of our last 93). Local complications were: 1 meningitis, 8 cases of CSF
      leakage requiring either a series of lumbar punctures or a lumbar external drain,
      and 3 cases of wound infection and/or delayed woundhealing requiring surgical
      treatment. CONCLUSIONS: Our data are consistent with those of the literature,
      especially concerning high rate of long-term success and low complication rate of
      MVD for HFS. We do not recommend early re-operation in case of initial poor
      result. Again, the necessity of intraoperative BAEP monitoring to prevent hearing
      morbidity is highlighted.

PMID- 14646819
TI  - [Cervical medullary metastasis in a patient with Von Hippel-Lindau disease].
AB  - Von Hippel-Lindau disease is an autosomal dominant disorder mainly characterized
      by hemangioblastoma(s) associated with kidney clear-cell carcinoma.
      Hemangioblastoma represents 2 to 3% of all central nervous system tumors whereas
      extramedullary metastasis accounts for 30 to 50% of all intravertebral column
      tumors. The most common sites of metastatic dissemination in order of frequency
      are the lung, breast, prostate and kidney. We report a case of an unusual
      cervical intradural extramedullary metastasis of clear-cell kidney carcinoma
      associated with a cervical spinal cord hemangioblastoma in a 45-year-old patient
      with Von Hippel-Lindau disease who had developed retinal hemangioblastomas 20
      years earlier. A review of the relevant literature is proposed.

PMID- 14646820
TI  - [Paraganglioma of the latero-sellar area. Case report].
AB  - Paraganglioma of the sellar and latero-sellar area is extremely rare. We report a
      case of latero-sellar and suprasellar paraganglioma of a 58-year-old women which
      caused deterioration of visual acuity and left exophthalmia without endocrine
      dysfunction. Magnetic resonance imaging showed a large tumor in the sellar and
      parasellar area, which extended to the left cavernous sinus and infiltrated the
      left orbit, the ethmoid, the sphenoidal sinus and the left pterygomaxillary
      fossa. Surgery by transcranial, left frontotemporal approach, enabled subtotal
      removal. Definitive histologic examination revealed a paraganglioma with signs of
      anaplasis. We report our clinical findings and present a review of literature.

PMID- 14646822
TI  - [Diagnosis and treatment of glaucoma].

PMID- 14646821
TI  - Capillary hemangioma of the spinal cord. Comment on the article by M. Rivierez et
      al.

PMID- 14646823
TI  - [HRT and glaucoma surgery follow-up].
AB  - Heidelberg Retina Tomography (HRT) analysis of the optic nerve might be
      temporarily modified after glaucoma surgery. However, optimal follow-up of
      glaucoma patients requires comparing reliable optic nerve images. The aim of this
      study was to define the consequences of glaucoma surgery on HRT measurements.
      Results showed temporary modifications until at least the third month, suggesting
      that it is better to wait 6 months after surgery to obtain reliable measurements.

PMID- 14646824
TI  - [Glaucoma and uveitis].
AB  - In uveitis, ocular hypertension may have different meanings. Before
      corticotherapy, hypertensive uveitis has specific etiologies. During
      corticotherapy, hypertensive uveitis or ocular hypertension related to
      corticotherapy may be involved. Intra-ocular pressure monitoring is mandatory in
      uveitis and during corticotherapy.

PMID- 14646825
TI  - [Should the ophthalmologist prescribe generic drugs?].
AB  - It seems obvious that an ophthalmologist should encourage the use of generic
      drugs. However, it is important to know the exact definition of a generic drug
      and the type of studies to be conducted before a generic drug is released on the
      market. A generic drug is a drug that has the same composition quantitatively as
      well as qualitatively of the active compound as the original drug. It also has
      the same pharmaceutical mode of action and the same bioavailability, as
      determined with bioavailability studies. Ophthalmic drops contain both an active
      compound and many adjuvants used to stabilize the drug. Globally speaking, the
      active compound corresponds to the efficacy of a topical drug and the adjuvant to
      its tolerance. It is likely that the efficacy of a generic drug is identical to
      that of the brand-name drug, even though only bioavailability studies in non
      human models are required to evaluate tolerance which is less likely to be
      identical, as adjuvants can differ. A survey of 520 French ophthalmologists has
      recently been conducted. It shows that doctors rarely think of prescribing
      generic drugs, as they do not consider cost as a major issue in treating
      glaucoma. However, they see no reason not to prescribe generic drugs. This mixed
      perception is shared by patients who willingly accept that doctors prescribe a
      generic drug, but do not wish the pharmacist to take the initiative of filling a
      prescription with a generic drug, which sometimes gives patients the impression
      of being less well treated. The use of generic drugs should be encouraged,
      keeping in mind that good tolerance should be ensured.

PMID- 14646826
TI  - [I have tested it for you....the Smartlens].
AB  - The SmartLens tonometer (ODC, Zurich, Switzerland) is a contact lens that allows
      continuous measurement of intraocular pressure (IOP), in addition to estimating
      pulse amplitude. IOP measurements taken with the Smartlens tonometer showed a
      good correlation with Goldmann tonometry. Nevertheless, there was a mean
      difference of 3.5 mmHg (p<0.01) in intraocular pressure between the two methods,
      with a significant overestimation by Smartlens tonometry compared with Goldmann
      tonometry in normal individuals. Preliminary results demonstrated that IOP
      measurements are not statistically affected by the thinning of the cornea induced
      by LASIK surgery.

PMID- 14646827
TI  - [Management of non penetrating surgery failure].
AB  - Failure of deep sclerectomy with external trabeculectomy is defined as
      intraocular pressure (IOP) elevation in the post-operative period. This IOP
      increase is related to obstacles on the outflow pathway, which may be hindered
      either by internal obstacles (iris incarceration, internal trabecular layers
      insufficiently permeable to aqueous humor), or by external obstacles (excessive
      conjunctival scar such as fibrosis or cysts). These obstacles require specific
      treatment that is not always successful. Pre-, intra- and post-operative care
      that reduces the incidence of these complications is detailed.

PMID- 14646828
TI  - [Optic disk drusen: what are the advantages of the new imaging techniques?].
AB  - This study reports four clinical cases of papillary drusen associated with OHT.
      The authors show the advantages of HRT, OCT2, and GDx for exploring the optic
      nerve and/or the retinal nerve fiber layer (RNFL). The repercussions of drusen on
      the optic nerve head may precede visual field failure. Better knowledge of the
      interpretation of these new imaging techniques may help define the respective
      roles of drusen and OHT, in case of visual field attack, and treatment
      modalities. These new procedures may help us to monitor drusen and their
      progression potential.

PMID- 14646829
TI  - [Glaucoma and high-frequency ultrasound].
AB  - The iridocorneal angle and the ciliary body are imaged with high precision using
      high-frequency ultrasound. A long-focus 20-MHz probe provides high-resolution
      imaging of the optic disk and optic nerve. These improvements mean that
      glaucomatous patients can be imaged by ultrasound with increased precision.

PMID- 14646830
TI  - [Glaucoma and quality of life].
AB  - Glaucoma is a serious ocular disorder potentially leading to blindness. Measuring
      the quality of life of patients with glaucoma is important because it makes it
      possible to evaluate the impact of the disease and its treatment on the patient's
      everyday life. Hitherto, this was done using generic scales, or those developed
      for other diseases; but no scale suitable for glaucoma was available. The
      recently developed GlauQOL scale is now available. We present the short version
      of this questionnaire adapted to individual use within an ophthalmology
      consultation setting.

PMID- 14646831
TI  - [Pigmentary dispersion: is iridectomy useful?].
AB  - Several clinical reasons induced Campbell to propose an iridotomy in cases of
      pigmentary dispersion: removing the inverse pupillary block, balancing pressures
      through the iris, and finally stopping the posterior erosion of the iris leading
      to pigmentary release. It is likely that certain failures in this method stem
      from an erroneous evaluation of the cases that could benefit from iridal
      perforation. Three conditions are required for this procedure to be successful:
      established ocular hypertension, an abnormally concave iris base, and absence of
      patent glaucoma.

PMID- 14646832
TI  - [Angle-closure chronic glaucoma].
AB  - The incidence of chronic angle closure glaucoma is considerably greater than the
      incidence of the acute type. This type of glaucoma may mimic primary open angle
      glaucoma with visual field deterioration, optic nerve alteration and intraocular
      pressure elevation with a quiet painless eye. Its diagnosis is based on
      indentation gonioscopy showing peripheral anterior synechiae. The mechanisms of
      angle closure are the pupillary block, the plateau iris configuration and the
      creeping form. The treatment of chronic angle closure glaucoma is based on laser
      peripheral iridotomy.

PMID- 14646833
TI  - [How to conduct glaucoma therapy when pressure stays high despite topical
      treatment?].
AB  - When glaucoma worsens with elevated ocular pressure despite an initial treatment,
      an additional reduction of pressure is needed. It is necessary to evaluate the
      cause of the therapeutic failure which could be the consequence of a low
      compliance from the patient, a poor efficacy of the topical drug or a short or
      long term drift of this efficacy. Depending on the aetiology, another monotherapy
      or a combination of treatments should be initiated. The evaluation of the target
      pressure and the comparison between this pressure and the current pressure of the
      eye allows to evaluate the likeliness of reaching the target through medical
      treatment alone or through surgical approach. When medical treatment is possible,
      it is usual to combine two drugs, one acting on the aqueous humor inflow and the
      other one on the uveoscleral outflow pathway. If target pressure is lower than
      what can be expected to be reached with topical treatment, surgery should be
      proposed to the patient. Laser Argon trabeculoplasty keeps still some
      indications, like pigmentary or exfoliative glaucoma. Long term stability of the
      visual field in glaucoma depends more on the reduction of pressure and on its
      stability than on the choice of medical or surgical approach.

PMID- 14646835
TI  - Causes of obesity. There can be more to it than overeating.

PMID- 14646834
TI  - [The refractory glaucomas].
AB  - Refractory types of glaucoma continue to present a therapeutic challenge to
      ophthalmologists. Approaches toward the management of these difficult glaucomas
      are addressed in this paper. The first part devotes special attention to
      understand the cause(s) of the failure of previous filtering surgery(ies). The
      next part emphasizes filtration surgery with intraoperative application of
      antimetabolites: 5-fluorouracil or mitomycin C and the surgical and
      pharmacological management of failing filtration. In case of failure of multiple
      filtering surgery with application of antimetabolites, surgeons have to consider
      cyclodestructive procedures (transscleral diode laser or endoscopic
      cyclophotocoagulation) to reduce aqueous production, or fistulizing procedures
      with tube implants or other drainage devices (valves).

PMID- 14646836
TI  - Experimental test for women at high risk of breast cancer.

PMID- 14646837
TI  - Oats and soy may cut cholesterol level.

PMID- 14646839
TI  - M.D., D.O., P.A., N.P. Deciphering medical credentials.

PMID- 14646838
TI  - Too heavy. Serious treatments for the seriously overweight.

PMID- 14646840
TI  - Vitiligo.

PMID- 14646841
TI  - Hypnosis. Deep relaxation can relieve pain and more.

PMID- 14646842
TI  - One on one. Can you explain sun protection factors and how they work to protect
      your skin?

PMID- 14646843
TI  - One on one. What is melatonin and what's it used for?

PMID- 14646845
TI  - Mayo Clinic office visit. Cholesterol-lowering drugs.

PMID- 14646844
TI  - One on one. I heard about a menopause home test kit. Is it worth taking?

PMID- 14646846
TI  - The 5 best stress management techniques (because you don't have time for 10).

PMID- 14646847
TI  - Advances in breast cancer treatment. Ongoing research offers options and hope.

PMID- 14646848
TI  - Working nights linked to increased breast cancer risk.

PMID- 14646849
TI  - Antioxidant supplements plus zinc may slow age-related macular degeneration.

PMID- 14646850
TI  - Older people can benefit from colon cancer chemotherapy, too.

PMID- 14646851
TI  - Common anorectal problems. Treatment and self-care solutions.

PMID- 14646853
TI  - Piriformis syndrome.

PMID- 14646852
TI  - Bursitis. Stress and overuse can cause inflammation.

PMID- 14646855
TI  - One on one. I heard there was a shortage of tetanus vaccine. Does this put me at
      greater risk of getting tetanus?

PMID- 14646854
TI  - Golf. Fresh air, fun and a workout, too.

PMID- 14646857
TI  - One on one. I heard about new contact lenses you can wear for 30 days - even
      while asleep. How safe are they?

PMID- 14646856
TI  - One on one. Does wearing foundation makeup protect my skin from the sun's harmful
      rays?

PMID- 14646859
TI  - Advances in breast cancer screening and prevention. Ongoing research offers hope.

PMID- 14646858
TI  - Mayo Clinic office visit. Age-related eye conditions.

PMID- 14646861
TI  - Drinking alcohol has mixed effects on the brain.

PMID- 14646860
TI  - Some antidepressants may cut heart attack risk.

PMID- 14646862
TI  - Are hysterectomy and estrogen use related to Parkinson's disease?

PMID- 14646863
TI  - Cosmetic dentistry. The best techniques for a winning smile.

PMID- 14646865
TI  - Reading food labels. What they do and don't reveal.

PMID- 14646864
TI  - Hysterectomy alternatives for uterine bleeding.

PMID- 14646866
TI  - One on one. What can I do to help relieve annoying leg cramps?

PMID- 14646867
TI  - One on one. How many calories should I eat each day to maintain my weight? How
      many if I want to lose weight?

PMID- 14646868
TI  - Mayo Clinic office visit. Orthopedic injuries.

PMID- 14646869
TI  - The evolution of the annual checkup.

PMID- 14646870
TI  - Eating fish cuts heart disease risk in women.

PMID- 14646871
TI  - Fish oil supplements may protect your heart, too.

PMID- 14646872
TI  - Increasing body weight linked to risk of congestive heart failure.

PMID- 14646873
TI  - Your mind. Experiencing the emotional and cognitive changes of midlife.

PMID- 14646874
TI  - Seborrheic dermatitis. Treating this oily, scaly skin disorder.

PMID- 14646875
TI  - Trigeminal neuralgia.

PMID- 14646877
TI  - One on one. What are age spots and how can I get rid of them?

PMID- 14646876
TI  - Stocking your home gym. Ounces of prevention, gallons of fitness fun.

PMID- 14646878
TI  - One on one. I read that potassium iodide can protect me from cancer if I'm
      exposed to radiation from a nuclear power plant. Should I keep some of these
      pills on hand?

PMID- 14646879
TI  - Mayo Clinic office visit. Getting the most out of your doctor visit.

PMID- 14646880
TI  - Menopause and hormone therapy. Making important choices at an important time of
      transition.

PMID- 14646881
TI  - Insulin resistance syndrome. Altered sugar processing leads to a multitude of
      medical problems.

PMID- 14646882
TI  - Surgery reduces cancer risk to women with BRCA gene mutations.

PMID- 14646883
TI  - New imaging technique for breast cancer detection.

PMID- 14646885
TI  - Fecal incontinence. Don't shy away from seeking help.

PMID- 14646884
TI  - People with diabetes cautioned about taking metformin.

PMID- 14646886
TI  - Fatty liver disease. A potentially preventable cause of cirrhosis.

PMID- 14646887
TI  - Dyspareunia.

PMID- 14646888
TI  - Fitting eggs into a healthy diet.

PMID- 14646889
TI  - One on one. Can I use vaginal estrogen cream on my face to diminish wrinkles?

PMID- 14646890
TI  - One on one. I sometimes leak urine when I exercise. Is there anything I can do to
      prevent this from happening?

PMID- 14646891
TI  - Mayo Clinic office visit. Polycystic ovary syndrome (PCOS).

PMID- 14646893
TI  - Women with diabetes less likely to get mammograms.

PMID- 14646892
TI  - Uterine fibroids. Common, noncancerous uterine tumors.

PMID- 14646894
TI  - Drinking tea may benefit people who've had heart attacks.

PMID- 14646895
TI  - Gene linked to effectiveness of blood pressure medication.

PMID- 14646897
TI  - Atrophic vaginitis. A treatable cause of vaginal dryness.

PMID- 14646896
TI  - Circadian rhythms. How your body's internal clock affects your health.

PMID- 14646899
TI  - Weather and your health. What's in the forecast for you?

PMID- 14646898
TI  - Spasmodic dysphonia.

PMID- 14646900
TI  - One on one. Are tanning beds really as bad for you as people say?

PMID- 14646901
TI  - One on one. Is there anything that can make mammograms more comfortable?

PMID- 14646902
TI  - One on one. Can I become mineral deficient if I drink only bottled water?

PMID- 14646903
TI  - Mayo Clinic office visit. Varicose veins.

PMID- 14646905
TI  - Mayo Clinic develops new rapid rest for anthrax.

PMID- 14646904
TI  - Emerging risk factors for heart disease. Newer indicators may create a better
      picture for who's at risk.

PMID- 14646906
TI  - Possible help for cough associated with ACE inhibitors.

PMID- 14646907
TI  - Stiff aortic valve may predict risk of stroke and atherosclerosis.

PMID- 14646908
TI  - Food-borne infections. Stopping bad bugs before they bite.

PMID- 14646909
TI  - Latex allergies. Potentially dangerous, increasingly common.

PMID- 14646910
TI  - Thalassemia.

PMID- 14646911
TI  - Addictions: What do they have in common?

PMID- 14646913
TI  - One on one. Is it true that eating blueberries will help my memory?

PMID- 14646912
TI  - One on one. I heard that wearing a bra may increase my risk of breast cancer. Is
      this true?

PMID- 14646915
TI  - Mayo Clinic office visit. Coping with bioterrorism.

PMID- 14646914
TI  - One on one. Should I consider having magnetic resonance imaging (MRI) if I'm at
      risk of breast cancer, even if I have to pay for it myself?

PMID- 14646916
TI  - Women are different from men. It's a matter of biology.

PMID- 14646917
TI  - A message from your medical editors about hormone therapy.

PMID- 14646918
TI  - Fainting. When it spells trouble and when it doesn't.

PMID- 14646919
TI  - Heartburn. When does it become dangerous?

PMID- 14646920
TI  - Fitness balls. Round out your exercise program.

PMID- 14646921
TI  - One on one. Why do I yawn? Is it really contagious?

PMID- 14646923
TI  - One on one. Are there blood tests to detect genital herpes? Are they accurate?

PMID- 14646922
TI  - One on one. How can I prevent eyestrain with prolonged computer use?

PMID- 14646924
TI  - Mayo Clinic office visit. Hair loss.

PMID- 14646925
TI  - The ABCs of hormone therapy preparations.

PMID- 14646927
TI  - Beta blockers help women battle heart failure.

PMID- 14646926
TI  - Once-a-year medication for osteoporosis.

PMID- 14646929
TI  - Hereditary cancers in women. Understanding and managing your risk.

PMID- 14646928
TI  - The link between high blood pressure and headaches questioned.

PMID- 14646930
TI  - Advances in anesthesia.

PMID- 14646931
TI  - Whole-grain bread. High in nutrition, low in fat and calories.

PMID- 14646933
TI  - Mayo Clinic office visit. Hearing loss.

PMID- 14646932
TI  - Flattening tummy bulge.

PMID- 14646935
TI  - Weighing your health risks. Putting your true risks into perspective.

PMID- 14646934
TI  - Joint health. Keep them moving through life.

PMID- 14646936
TI  - Snacking linked to lower cholesterol levels.

PMID- 14646937
TI  - Lifestyle changes and medications may help prevent diabetes.

PMID- 14646939
TI  - Urinary tract infections. Update on treatment and prevention.

PMID- 14646938
TI  - Can mental stimulation cut your risk of Alzheimer's disease?

PMID- 14646941
TI  - Deep breathing. A relaxation technique that may provide health benefits.

PMID- 14646940
TI  - The sunshine vitamin.

PMID- 14646942
TI  - One on one. What causes trigger finger, and what can be done for it?

PMID- 14646943
TI  - One on one. Can I measure my blood pressure at home?

PMID- 14646944
TI  - Mayo Clinic office visit. Practical aspects of antibiotic use.

PMID- 14646945
TI  - Triglycerides. Understanding what your levels mean to your health.

PMID- 14646946
TI  - Untangling the mammogram muddle.

PMID- 14646947
TI  - Tired all of the time. Understanding and managing fatigue.

PMID- 14646948
TI  - Living with lupus.

PMID- 14646949
TI  - Exercise. What's in it for you, physiologically speaking?

PMID- 14646950
TI  - One on one. I'm thinking of getting permanent makeup. Are there any risks I
      should be aware of?

PMID- 14646951
TI  - One on one. How often do I need to repeat bone density testing after menopause?

PMID- 14646952
TI  - One on one. I recently heard that homocysteine levels may be related to
      Alzheimer's disease. Should I have mine checked?

PMID- 14646953
TI  - Mayo Clinic office visit. Depression antidepressants.

PMID- 14646954
TI  - Migraines. Managing your pain.

PMID- 14646955
TI  - Is there a link between multiple sclerosis and the Epstein-Barr virus?

PMID- 14646956
TI  - Fertility drugs may not increase risk of invasive ovarian cancer.

PMID- 14646957
TI  - Common painkiller may hinder aspirin's heart benefits.

PMID- 14646958
TI  - Steroids. The good and the bad.

PMID- 14646959
TI  - Hernias. Abdominal weaknesses can lead to protrusions.

PMID- 14646960
TI  - Polymyalgia rheumatica.

PMID- 14646961
TI  - Healthy eating. Nutritional needs change with age.

PMID- 14646962
TI  - One on one. I have a burning sensation in my mouth. What is it and what can be
      done for it?

PMID- 14646963
TI  - One on one. Could a poorly fitting bra cause rib pain?

PMID- 14646964
TI  - One on one. What's coenzyme Q-10 and what's it used for?

PMID- 14646965
TI  - Mayo Clinic office visit. An Olympic experience.

PMID- 14646966
TI  - RhoA expression is not a critical determinant in hypertension evolution in salt
      sensitive Dahl rats.
AB  - BACKGROUND: The Rho/Rho kinase pathway plays an important role in regulation of
      vascular smooth muscle cell contraction and is involved in the pathogenesis of
      hypertension. However, little is known about the role of this pathway in the
      evolution of salt-sensitive hypertension and vascular remodeling. The aim of this
      study was to examine whether the age-dependent surge of blood pressure after
      exposure to a high salt-containing diet, which is well-established for Dahl salt
      sensitive rats, is primarily regulated by the level of expression of RhoA in
      arterial vessels. MATERIAL/METHODS: We examined Dahl salt-sensitive rats at 3
      weeks, 6 weeks, and 9 weeks of age (n=10, each). In each group, animals were
      switched to being fed a diet containing 8% NaCl from one containing 0.3% NaCl.
      After 7 days, mRNA and protein levels of RhoA from the thoracic aorta were
      quantified. RESULTS: At the time of examination, increases in systolic blood
      pressure were significantly different depending on the age at which the high salt
      diet was initiated. The % increases were 34+/-3% (3-weeks), 20+/-2% (6-weeks),
      and 13+/-2% (9-weeks). Despite these differing changes in blood pressure, mRNA
      and protein levels of RhoA in the arteries did not differ among the groups.
      CONCLUSIONS: RhoA expression and activity appear not to be the critical
      determinant of the surge in hypertension when Dahl salt-sensitive rats are
      exposed to salt-rich diets. Hence, the age-dependent salt-sensitivity must be
      mediated by alternative pathways.

PMID- 14646967
TI  - The existence of an NAD-dependent pathway for retinoic acid formation from
      vitamin A (retinol) in rat esophagus and its inhibition by ethanol and histamine
      2 (H2) receptor antagonists.
AB  - BACKGROUND: Retinoic acid is essential for normal cell differentiation and
      proliferation and disturbance of its metabolism has been implicated in the
      pathogenesis of various disorders including malignancy. Retinoic acid has been
      demonstrated to be produced from retinol via a two step oxidation pathway in
      which alcohol dehydrogenase isozymes have roles. The aim of this study was to
      know whether the rat esophagus would have the pathway and whether the retinoic
      acid formation could be disturbed when alcohol dehydrogenase was hampered.
      MATERIAL/METHODS: Rat esophageal cytosolic fraction, nicotinamide adenine
      dinucleotide, and all-trans retinol were incubated together and produced all
      trans retinoic acid was detected by high performance liquid chromatography
      method. RESULTS: Remarkable all-trans retinoic acid formation was observed only
      when nicotinamide adenine dinucleotide was in existence. The all-trans retinoic
      acid formation was hampered by addition of ethanol, another substrate of alcohol
      dehydrogenase, and some histamine 2 receptor antagonists, inhibitors of alcohol
      dehydrogenase. CONCLUSIONS: These results suggest that rat esophagus has an
      nicotinamide adenine dinucleotide-dependent all-trans retinoic acid formation
      pathway in which alcohol dehydrogenase is involved. We hypothesize that
      disturbance of the all-trans retinoic acid formation pathway by ethanol and
      histamine 2 receptors may cause various esophageal disorders including esophageal
      cancer seen in alcoholics and subjects taking histamine 2 receptors excessively.

PMID- 14646968
TI  - Quantitative assessment of immediate cutaneous hypersensitivity in a mouse model
      exhibiting an IgE response to Timothy grass allergens.
AB  - BACKGROUND: A variety of allergic reactions can be induced in mice, as measured
      by the induction of specific IgE. Functional read-out parameters include skin
      reactions and airway constriction. The aim of this study was to establish an
      improved quantitative assessment of the immediate cutaneous hypersensitivity
      reaction in a mouse model. MATERIAL/METHODS: Timothy grass pollen was used to
      sensitize BALB/c mice, which were monitored for hypersensitivity reactions by
      Western blot analysis of the IgE response, determination of specific
      immunoglobulin subclasses by ELISA, and a skin test. The immediate cutaneous
      hypersensitivity reaction (ICHR) was assessed by pretreating the animals with an
      intravenous injection of Evans blue before anesthesia and provoking a reaction by
      intradermal application of the allergen. Ensuing blue coloring at the injection
      site could be seen as an indication of mast cell degranulation and the areas of
      'wheal and flare' reaction were documented for digital imaging and quantitative
      analysis. RESULTS: Analysis using an antigen-specific ELISA showed that
      sensitization with pollen extract induced the production of specific IgE, IgG1,
      IgG2a and IgG2b antibodies. Western blot analyses demonstrated the production of
      specific IgE antibodies analogous to the IgE reactivity pattern found in allergic
      patients. The production of IgE was concurrent with a positive ICHR to these
      allergens. Quantitative analysis demonstrated that the area of ICHR increased in
      size in correlation to the dose of allergen applied. CONCLUSIONS: This model and
      the mode of skin reactivity analysis may serve as a tool to evaluate new
      hyposensitization and therapeutic strategies for pollen allergy.

PMID- 14646969
TI  - Age related natural antiviral non-specific immunity of human leukocytes.
AB  - BACKGROUND: The purpose of our study was to examine the dependence of innate
      antiviral immunity on age and sex in human leukocytes. MATERIAL/METHODS: Innate
      antiviral immunity was measured by using the direct method of infection of
      leukocytes with vesicular stomatitis virus (VSV), which was selected as the
      indicatory virus for detection of immunity. The lack of VSV replication by
      infected leukocytes (0-1 log TCID50) was taken as an indicator for complete
      immunity; a low level of VSV replication (2-3 log) for partial immunity; and a
      high VSV titer (4 or more log) for the no or very low immunity. RESULTS: The
      kinetics of VSV replication was studied in leukocytes isolated from 127
      individuals ranging in a age from 0 to 89 years. Individual differentiation in
      the kinetics of VSV replication indicated differing degrees of innate immunity
      even in newborns. Age-related differences in natural immunity were observed: low
      immunity in newborns, highest in the age group 31-40, and reduced in the age
      group >60. Sex dependent innate immunity was shown in the group of aged persons,
      as innate immunity was higher in women than in men. CONCLUSIONS: Innate immunity
      of leukocytes develops to age 30-40, after which immunity is gradually reduced.
      Sex dependence was observed only in the group of elderly persons, where women
      expressed higher immunity; this is probably a reason for their statistically
      greater longevity.

PMID- 14646970
TI  - Stimulation of sensory nerves and CGRP attenuate pancreatic damage in
      ischemia/reperfusion induced pancreatitis.
AB  - BACKGROUND: Previous studies have shown that sensory nerves and calcitonin gene
      related peptide (CGRP) affect caerulein-induced pancreatitis. The aim of this
      study was to examine the role of capsaicin-sensitive nerves and the impact of
      CGRP administration on necrotizing pancreatitis induced by ischemia/reperfusion.
      MATERIAL/METHODS: Ablation of sensory nerves was made by capsaicin 10 days before
      induction of pancreatitis. Acute pancreatitis was induced in rats by limitation
      of pancreatic blood flow (PBF) followed by reperfusion. Treatment with saline or
      CGRP (10  g/kg s.c.) or stimulation of sensory nerves by low doses of capsaicin
      (0.5 mg/kg s.c.) was performed 1 h before ischemia. After 1 h reperfusion we
      examined pancreatic blood flow (PBF), plasma amylase and lipase activity, plasma
      interleukin-1beta (IL-1beta) concentration, pancreatic DNA synthesis and
      morphological signs of pancreatitis. RESULTS: Ischemia followed by 1 h
      reperfusion led to induction of necrotizing pancreatitis, manifested by
      morphological signs of pancreatic damage, decrease in pancreatic DNA synthesis
      and PBF, as well as an increase in plasma amylase and lipase activity and plasma
      IL-1beta concentration. Both, treatment with CGRP and stimulation of sensory
      nerves attenuated pancreatic damage. Ablation of sensory nerves enhanced I/R
      evoked pancreatic damage. The deleterious effect of deactivation of sensory
      nerves on I/R-induced pancreatitis was partly reversed by administration of CGRP
      prior to I/R. CONCLUSIONS: Stimulation of sensory nerves protects the pancreas
      against damage evoked by I/R, whereas ablation of these nerves aggravates tissue
      damage in the pancreas exposed to I/R. The beneficial effect of sensory nerves is
      partly dependent on CGRP release.

PMID- 14646971
TI  - Missense mutation of exon 3 in the type A human natriuretic peptide receptor gene
      is associated with myocardial infarction.
AB  - BACKGROUND: Myocardial infarction (MI) is a complex multifactorial and polygenic
      disorder that is thought to result from interaction between genetic make-up and
      various environmental factors. We previously identified a missense mutation,
      methionine (ATG) to isoleucine (ATC) at nucleotide 1023 (M341I), in exon 3 of the
      human natriuretic peptide receptor A type (hNPRA) gene. This mutation is
      associated with increased risk for essential hypertension (EH). The purpose of
      this study was to investigate association between MI and the M341I mutation in
      the hNPRA gene. MATERIAL/METHODS: The study population included 305 healthy
      control subjects and 230 patients with MI, all of whom were below the age of 70
      years. To assess the identified mutation in the target exon using Taq I
      restriction fragment length polymorphism (RFLP), specific primers were utilized.
      Based on the results of the PCR-RFLP, we developed a convenient and automatic
      method for genotyping by allelic discrimination using TaqMan PCR chemistry.
      RESULTS: Multiple logistic linear regression analysis showed significant
      difference in genotype distribution between the control and MI groups. Overall
      distribution of alleles also differed significantly between the MI and control
      groups (p=0.028). The C allele was found more frequently in the MI group than in
      the control group. CONCLUSIONS: We conclude that the M341I missense mutation is
      associated with risk for MI and may be a genetic marker of MI in Japanese people.

PMID- 14646972
TI  - An investigation of nitric oxide metabolites during symptomatic myocardial
      ischaemia in relation to exercise tolerance test.
AB  - BACKGROUND: Nitric oxide (NO) plays a pivotal role in the pathophysiology of
      coronary heart disease (CHD). Low plasma concentrations of NO metabolites
      (nitrite and nitrate), the stable oxidation products of NO have been reported in
      patients with CHD but this is controversial. Plasma nitrite and nitrate
      concentrations during symptomatic myocardial ischaemia and in response to
      exercise in subjects with CHD have not been studied. We therefore measured plasma
      nitrite and nitrate concentrations in subjects before and after an exercise
      tolerance test (ETT). MATERIAL/METHODS: Plasma nitrite and nitrate concentrations
      were measured before and after an ETT in 24 subjects with symptomatic exercise
      induced myocardial ischaemia (positive ETT) and in 27 subjects without exercise
      induced myocardial ischaemia (negative ETT). RESULTS: Plasma nitrate
      concentrations were higher (p<0.002) before and after the ETT in subjects with a
      positive ETT (31.51+/-21.80 mol/L and 30.86+/-21.42 mol/L respectively) than in
      the subjects with a negative ETT (14.75+/-6.71 mol/L and 15.64+/-6.50 mol/L
      respectively). Plasma nitrite concentrations before and after the ETT were
      similar in both groups. Within each group, plasma nitrite and nitrate
      concentrations were not altered by exercise. CONCLUSIONS: Subjects with exercise
      induced myocardial ischaemia have higher plasma nitrate concentration than
      subjects without exercise-induced myocardial ischaemia. This is consistent with
      either a compensatory or an inflammatory response of the vascular endothelium to
      endothelial damage. Symptomatic exercise-induced ischaemia is not associated with
      altered plasma NO metabolite concentrations.

PMID- 14646973
TI  - Anticardiolipin antibody of adolescents and age of myocardial infarction in
      parents.
AB  - BACKGROUND: The objective of our research was to study anticardiolipin antibody
      (ACLA) in the offspring of families at high risk for premature coronary heart
      disease (CHD) in comparison to controls, and the degree of agreement between ACLA
      levels in parents and children. MATERIAL/METHODS: In an analytical case-control
      study, three paired parent-child groups of 50 each were selected by simple random
      sampling, and their IgG ACLA levels measured by ELISA method. A comparison was
      made between parents who had premature myocardial infarction (MI<55 years of age)
      and one child aged between 12 to 19 years as the case group, parents with MI>55
      years and one child, and parents with no history of heart attacks and one child
      as the first and second control groups, respectively. RESULTS: The prevalence of
      positive ACLA in adolescents in the case group was significantly higher than the
      second control group (P=0.03), but this difference was not significant against
      the first control group (p>0.05). Regarding parents, there were significant
      differences between the case group and both control groups (P=0.04 and P=0.009,
      respectively). A substantial degree of correlation was found between positive
      ACLA in patients with premature MI and their children (kappa correlation
      coefficient =0.63, 95% CI, 0.47-0.79). CONCLUSIONS: The findings of this study
      point to the probable presence of a familial immunological background in the
      onset of premature atherosclerosis with regard to ACLA, which can be measured as
      a risk factor in predicting premature CHD.

PMID- 14646974
TI  - Severity of coronary artery disease in patients with acute coronary syndrome
      without ST segment elevation is related to baseline troponin I and ST-segment
      depression.
AB  - BACKGROUND: Risk assessment for patients admitted with acute coronary syndrome
      (ACS) is usually based on the past medical history, along with several clinical
      and biochemical criteria. We hypothesised that stratification of patients with
      ACS according to the presence of ST-segment depression and results of a
      qualitative troponin I test would identify subjects with more severe disease who
      may benefit from an earlier, more aggressive strategy. MATERIAL/METHODS: The
      study group consisted of 115 patients hospitalized for typical chest pain (>5
      min) occurring within the last 24 hours, with coronary angiography. Blood was
      drawn for routine biochemistry and qualitative troponin I testing, and ECG was
      performed on admission. RESULTS: Patients were classified according to the
      presence of ST segment depression (ST) and the troponin I test results (T) into
      three categories: group A, consisting of 34 patients with ST+/T+; group B,
      consisting of 84 patients with either ST+/T- or ST-/T+; and group C, consisting
      of 7 subjects with ST-/T-. This stratification correlated significantly with the
      extent of coronary artery disease (p=0.0004). Significant coronary artery
      stenosis was significantly more prevalent in patients from groups A and B than in
      C (p<0.002). No difference in the patients' medical history, apart from more
      frequent AMI within the past 10 days in group A (p=0.009) was found between
      groups. CONCLUSIONS: Admission assessment of ECG and troponin I tests in patients
      with ACS may identify subjects with significant coronary artery disease, who are
      at high risk and could benefit from aggressive therapy.

PMID- 14646975
TI  - Homocysteine level and other biochemical parameters in cardiovascular disease
      patients with diabetes mellitus.
AB  - BACKGROUND: Atherosclerosis is the main cause of cardiovascular morbidity and
      mortality in many countries. It is believed that hyperhomocysteinemia is a risk
      factor for premature atherosclerosis and other cardiovascular diseases (CVD) in
      both men and women. MATERIAL/METHODS: Plasma samples from 31 non-CVD and 51 CVD
      patients with diabetes were studied. Informed consent was obtained from all
      subjects. Blood samples were collected after overnight fasting. Total
      homocysteine (H [e]), the levels of high and low density lipoproteins (HDL, LDL),
      total cholesterol, urea and creatinine were determined with commercial kits.
      RESULTS: The levels of homocysteine, vitamin B12, creatinine, and urea in CVD
      patients were significantly higher than those found in the normal subjects. On
      the other hand, the levels of folic acid, HDL and LDL were lower in CVD patients
      than in normal subjects. Interestingly, a linear relationship was found between
      the levels of homocysteine and total cholesterol in CVD samples, whereas no such
      linear relationship was present in normal subjects. CONCLUSIONS: The level of
      homocysteine in plasma is known to be mainly dependent on the levels of folic
      acid and vitamin B12. However, in the present study the level of homocysteine in
      the plasma of CVD patients is dependent on the level of folic acid and not on the
      level of vitamin B12. Subjects with high homocysteine levels should be advised to
      consume a folic acid-fortified diet in order to reduce the homocysteine level in
      patients at high risk for cardiovascular disease.

PMID- 14646976
TI  - Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with
      pemphigus vulgaris and foliaceus and in healthy relatives.
AB  - BACKGROUND: Pemphigus is a life-threatening, autoimmune blistering disease,
      mediated by IgG autoantibodies. The aim of our study was to assess the usefulness
      of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating
      pemphigus autoantibodies, and to compare its sensitivity and specificity with the
      indirect immunofluorescence (IIF) test. We also established the frequency of
      occurrence of pemphigus autoantibodies in relatives of our patients.
      MATERIAL/METHODS: IIF and ELISA tests were performed in 24 patients with
      pemphigus vulgaris, 13 with pemphigus foliaceus, 56 healthy relatives, and 50
      controls, selected according to sex and age. RESULTS: The obtained results
      revealed high specificity and sensitivity of ELISA, comparable to the IIF test,
      especially in patients who were in the active stage of the disease. We also
      showed that the profile of anti-Dsg 1 and/or anti-Dsg 3 autoantibodies is
      associated with the clinical variant of pemphigus. The frequency of occurrence of
      pemphigus autoantibodies in the relatives (24/55) performed by IIF was
      significantly higher (p<0.001) than in the controls (0/50). The same antibodies
      detected by ELISA (11/56) were less frequent. CONCLUSIONS: In clinically doubtful
      cases, in which autoantibodies titres by IIF are equal on both substrates (monkey
      and guinea pig esophagus), the assessment of the exact antibody profile (anti-Dsg
      1 and/or anti-Dsg 3) is important to establish the subtype of pemphigus. The
      frequency of pemphigus antibody occurrence in healthy relatives seems not to be
      incidental, but further studies should be performed to explain this phenomenon.

PMID- 14646977
TI  - Seasonality of births and abortions in New South Wales, Australia.
AB  - BACKGROUND: Complex seasonal variations in abortions and seasonal trends have
      been reported worldwide, but there are no data from Australia. MATERIAL/METHODS:
      Hospital morbidity and birth data were modelled using time series and regression
      techniques to describe seasonal changes in births and abortions (1989-99) in NSW,
      Australia. Data were also analysed to determine demographic predictors of
      abortions. RESULTS: A higher proportion of births in NSW were recorded in March
      and September-October. Irrespective of the nuptiality the lowest seasonal indices
      were recorded in February and November. For married women aged 20-49 years,
      voluntary abortions were significantly higher in February (t=0.04) and
      significantly lower in April (t<0.001) and June (t=0.03) and non-voluntary
      abortions were significantly higher in February (t=0.002) and March (t=0.006).
      There was seasonality in voluntary abortions (F=4.3, p<0.001) and no seasonality
      in non-voluntary abortions (F=2.4, p=0.01) for never married women aged 20-49
      years. As similar to married women, voluntary abortions among never married women
      were significantly higher in February (t<0.001) and significantly low in April
      (t=0.009). The lowest number of abortions were in April. Non-voluntary abortions
      occurred mostly in March for married women. The average number of voluntary
      abortions were significantly higher for never married women than for married
      women. CONCLUSIONS: There was a significant seasonality of births and abortions
      in NSW, Australia, with a peak of conceptions in December/January. Abortions were
      lowest in April and non-voluntary abortions were peaked in March. These data
      suggest that the human reproductive behaviour has a close relationship with
      environmental factors.

PMID- 14646978
TI  - Passive acquired immunity against measles in infants born to naturally infected
      and vaccinated mothers.
AB  - BACKGROUND: Currently, the majority of newborns in Poland are born to mothers who
      have been immunized against measles. The aim of this study was to compare the
      maternal measles antibody titers of infants born to mothers who had been infected
      by measles wild virus (group I) with those born to mothers who had been
      vaccinated (group II). MATERIAL/METHODS: Serum samples were tested for measles
      antibodies from 79 infants in the 7th month of life and from 27 mothers between
      17 and 41 years of age. Two commercial enzyme immunoassays (EIA) and a plaque
      neutralization test (PNT) were used. RESULTS: Only 12.7% of all infants showed
      measles antibodies in EIA. However, antibodies could be detected by PNT in all
      the infants, although only 36.6% showed titers of >1:8, which corresponds to
      protective antibody values of >0.2 IU/ml. The mean geometrical titer was
      significantly higher among infants from group I than in group II (1:7.16 vs.
      1:3.71, p=0.0038). Protective antibody titers were detected in 50% of infants
      from group I and only 18.2% in group II (p<0.02). CONCLUSIONS: Passive acquired
      immunity in infants born to mothers who have had measles lasts longer than in
      infants born to vaccinated mothers. Nearly two thirds of infants (65.4%) in the
      7th month of life did not have sufficient maternally derived neutralizing
      antibodies to protect against measles. Our data suggest that the recommended age
      for the first dose of measles vaccine during measles epidemics should be lowered
      to 9 months, with re-vaccination at 12-15 months.

PMID- 14646979
TI  - Acute inflammation of a congenital cecal diverticulum mimicking appendicitis.
AB  - BACKGROUND: Cecal diverticulitis is a relatively rare problem in the Western
      world. It is often clinically indistinguishable from acute appendicitis. CASE
      REPORT: We present a case of a young woman who was suspected to have acute
      appendicitis prior to operation. At operation an unexpected and suspicious cecal
      mass was found and the procedure was revised to a right hemicolectomy. Subsequent
      histological examination revealed an acutely inflamed solitary, congenital
      diverticulum of the cecum. CONCLUSIONS: We would like to highlight this uncommon
      condition to ensure that its first encounter is not in the operating theatre. The
      varied and controversial management options are briefly discussed.

PMID- 14646980
TI  - Malignant lymphoma of the jaw bone.
AB  - BACKGROUND: Malignant lymphomas are neoplasms originating from lymphocytes, whose
      precursor cell or cells are generated during the multipotential differentiation
      of a stem cell. Extranodal localization most often involves the Waldeyer's ring,
      nasal cavity, maxillary sinuses, eyeballs, salivary glands, oral cavity, stomach
      or skin. Localization in the nervous system or facial bones is very rare. CASE
      REPORT: This article presents a rare case of a patient with B-cell
      lymphoplasmocytic lymphoma located in the jaw bones. The diagnosis was
      established after histopathological investigation of periapical lesions. Due to
      the localized growth of the malignant lymphoma, the patient underwent surgery
      combined with radiotherapy. The follow-up period amounted to 14 months and the
      patient now presents without recurrences or lymphadenopathy. CONCLUSIONS: All
      periapical lesions should be sampled for histopathological examination, possibly
      revealing a hidden neoplastic process.

PMID- 14646981
TI  - Polyurethanes and childhood asthma.
AB  - BACKGROUND: Asthma is the most common chronic disease of children. Its prevalence
      in affluent nations has steadily and dramatically increased in recent decades.
      Genetic and environmental factors play a role in development of atopy and asthma.
      Imbalance in the immune system favoring respiratory diseases has been linked to
      exposure to environmental stressors (e.g, biological and chemical) very early in
      life. Isocyanates, used in the production of polyurethane, can elicit asthma and
      produce immune responses (e.g, antibodies, cytokines, etc.) typical of atopy.
      MATERIAL/METHODS: Numerous medical materials that directly contact human neonates
      are constructed of polyurethanes. A detailed survey and listing of such materials
      was undertaken in the neonatal unit of a large urban hospital. Representative
      samples of polyurethane-containing materials were tested for isocyanate residues
      using a semi-quantitative colorimetric method. RESULTS: Isocyanate residues were
      detected in wound dressings, adhesive films, oximetry sensors, etc, that directly
      contact neonatal skin. CONCLUSIONS: Dermal exposure to polyurethane and, thus, to
      isocyanates could occur early in life through contact with medical materials. In
      an animal model, dermal exposure to isocyanates leads to dermal sensitization and
      asthma. We postulate that dermal contact with polyurethane-containing medical
      materials may be involved in dysregulation of the neonatal immune system and
      could predispose infants to the development of childhood asthma.

PMID- 14646982
TI  - The application of computer posturography in psychological diagnosis.
AB  - BACKGROUND: We analyzed assessment of equilibrium system efficiency versus
      organic test performance and dependence on functional aspect of cognitive and
      psychomotor functions. MATERIAL/METHODS: A population of 250 persons from 15 to
      65 years of age was examined. Measurements of the sense of balance were carried
      out by means of computer posturograph. Three parameters describing the
      posturographic trajectory (its variability over time) were selected for analysis:
      the resultant sway coefficient, average, and maximum sway speeds. CNS function
      was assessed against the background of tests results from the psychoorganic
      triad. Cognitive and psychomotor functions were evaluated on the basis of the
      Raven test, Digital Symbol test, Poppelreuter test, Toulous - Pieron test, and
      the cross-type apparatus, as well as measurement of direct reaction to auditory
      and visual stimuli. RESULTS: The results showed decreased efficiency of the
      equilibrium system in persons with poorer performance on organic tests and a
      lower level of cognitive and psychomotor functions. The analyzed parameters of
      the equilibrium system demonstrated a higher degree of dependence on the degree
      of organic alteration than on the location of defects within the central nervous
      system. CONCLUSIONS: The resultant sway coefficient proved to be the most useful
      parameter of equilibrium for diagnostic purposes.

PMID- 14646983
TI  - Use of contemporary biomarkers in the detection of chronic alcohol use.
AB  - Alcohol is the most commonly abused substance yet alcoholism is frequently
      undiagnosed. The misuse of alcohol is common and frequently an occult problem.
      More than 10% of current drinkers meet diagnostic criteria for alcohol abuse or
      dependence while the lifetime prevalence for these conditions in outpatient
      settings ranges from 16 to 36 percent. Long-term, heavy drinking is associated
      with significant morbidity, mortality, and economic costs. Clues to alcohol use
      can be discovered from a patient's history and physical stigmata. Validated
      screening instruments such as the Alcohol Use Disorders Identification Test
      (AUDIT), CAGE Questionnaire, and Brief Michigan Alcoholism Screening Tests help
      confirm the clinical suspicion of alcohol dependence. Laboratory abnormalities of
      mean corpuscular volume, gamma-glutamyl transferase, alkaline phosphatase, or
      alanine amino transferase levels are non-specific indicators of possible alcohol
      induced liver impairment. Newer, less well-known FDA-approved biochemical markers
      such as the Carbohydrate Deficient Transferrin and the Early Detection of Alcohol
      Consumption test may also be used to detect heavy alcohol abuse and to monitor
      relapse episodes. Brief interventions are successful, making identification and
      diagnosis a vital role for the family physician. Improved awareness of alcohol
      misuse, increased use of screening tools, and the appropriate use of biochemical
      markers will facilitate early intervention and successful management of patients
      with alcohol use disorders.

PMID- 14646984
TI  - The impact of periodontal infection on systemic diseases.
AB  - Systemic health is often closely linked to the state of the oral cavity: many
      systemic diseases and conditions have oral manifestations. Likewise, oral
      microbiological infections may also affect one's general health status. Indeed,
      animal and population-based studies now suggest that periodontal diseases may be
      linked with systemic diseases and conditions including cardiovascular diseases,
      diabetes, respiratory diseases, adverse pregnancy outcomes, and osteoporosis.
      Better understanding of this correlation will help both dental and medical
      professionals to determine the best approach to patient care. This review will
      focus on the current knowledge linking periodontal infections to a set of
      systemic diseases. While a number of interactions have been identified,
      additional research will be required to determine whether these associations are
      causal or coincidental, and to evaluate disease pathogenesis and potential
      therapeutic interventions. These findings place oral health in the perspective of
      systemic health, and they suggest that the dental and medical professions should
      develop even closer ties in the future.

PMID- 14646985
TI  - Non-pharmacological treatment for chronic obstructive pulmonary disease.
AB  - Evidence-based guidelines on treatment of patients with Chronic Obstructive
      Pulmonary Disease (COPD) have recently been developed. Non-pharmacological
      therapy of COPD has been receiving more interest and has been evolving rapidly in
      the last decade as an essential part of COPD treatment. In fact, non
      pharmacological treatment is a complementary approach mainly in the advanced
      stages of COPD. Most of these care options appear to benefit patients in terms of
      quality of life and cost-effectiveness. The aim of the present review is to
      survey the most important non-pharmacological treatments for COPD (smoking
      cessation, rehabilitation, long-term oxygen therapy, noninvasive positive
      pressure ventilation, and surgery) and their usefulness based on the currently
      available evidence. This review is based on an evaluation of the literature using
      a multimethod approach. A computerized MEDLINE search from 1966 through June 2003
      was undertaken using the search terms pulmonary rehabilitation, surgery, smoking
      cessation, respiratory insufficiency/failure, and lung disease/obstructive. Non
      pharmacological treatment of COPD is a real option to successfully treat these
      patients and prevent further deterioration. All the included therapies are based
      on actual scientific evidence for patient benefits. To date, smoking cessation,
      comprehensive rehabilitation and long-term oxygen therapy are widely accepted as
      therapies which may positively impact the long-term management of COPD patients.

PMID- 14646986
TI  - [Diagnostic imaging of bone tumors].

PMID- 14646987
TI  - [Description of the fast scan method in MRI].

PMID- 14646988
TI  - [Some advices for writing a scientific paper].

PMID- 14646989
TI  - [Clinical usefulness of limited cone beam X-ray CT for dental use in the cranio
      facial region].

PMID- 14646990
TI  - [A report of the parameter for SPECT images using iteration reconstruction
      method].

PMID- 14646992
TI  - [New hope for winning the war against cancer: IMRT=Intensity-Modulated-Radiation
      Therapy - Part 6 -].

PMID- 14646991
TI  - [Regarding techniques and method of experiential composition].

PMID- 14646993
TI  - [Evaluation of time resolution of primary visual cortex using a single paradigm:
      sequence design employing a stimulation system].
AB  - The characteristics of fMRI include high-resolution, non-invasiveness, and ease
      of use, making it increasingly popular for brain imaging. However, imaging by the
      block paradigm is limited in time resolution from stimulus presentation to the
      subject to image acquisition. Therefore, it is not necessarily adequate for the
      evaluation of early (initial) brain activity. To evaluate this activity, real
      time resolution during stimulation is required. We considered a single paradigm
      to be the most suitable for this purpose. To obtain real-time information at
      stimulation, it is necessary to utilize the sequence design of a single paradigm
      that synchronizes with an external trigger. By so doing, we found that it was
      possible to evaluate brain activity in the early stage in the primary visual
      cortex. The relative decrease of PO(2) ("sank") that was generated in the initial
      stage of BOLD, that is, the initial dip, was captured as a transitory change in
      signal by using a stimulation presentation of about two seconds in the single
      paradigm. Results showed that the single design provided time resolution with a
      high time to activation. Moreover, it is thought that imaging by a single
      paradigm that synchronizes with stimulation is indispensable for the time and
      spatial elucidation of detailed brain activity. Therefore, brain activity at the
      early stage in primary visual cortex was clarified by using a single paradigm
      that synchronized with stimulation from single-shot EPI.

PMID- 14646994
TI  - [Classification of observer-groups with cluster analysis and the criteria of
      visual decision for each group].
AB  - It is important that the evaluation of X-ray images include the observer's visual
      characteristics. However, evaluations of X-ray images that include these
      characteristics are not performed because of the difficulty of quantitatively
      elucidating visual characteristics. In this study, we classified observers into
      groups (clusters) by the same criteria of visual decision, using cluster analysis
      (unweighted Pair-Group method using arithmetic averages), and evaluated X-ray
      images on the basis of this separation. Clinical application is also discussed.
      It was found that observer clustering caused a decrease in between-observer
      variation. Observers were grouped into two different categories: one with the
      characteristics of radiologists and the other with the characteristics of medical
      physicists. Our results indicated that the group with the characteristics of
      radiologists was suitable for the quality control (QC) of X-ray images.

PMID- 14646995
TI  - [Development of an automated patient-recognition method for digital chest
      radiographs using edge-enhanced images].
AB  - It is important that all images in a picture archiving and communication system
      (PACS) environment should be stored in the correct location, e.g., in the proper
      patient's folder. However, if patient information, such as identification number
      or patient name, has been entered incorrectly, the image may be stored in the
      wrong place. We are developing an automated patient recognition method for chest
      radiographs based on a template-matching technique to prevent such filing errors.
      To further improve the performance of our method, we investigated the usefulness
      of a new automated patient-recognition method based on a template-matching
      technique by using edge-enhanced and smoothed images. We found that the
      relationship between the correlation values obtained with and without the edge
      enhancement technique tended to provide different criteria for identifying
      correct or incorrect patients. When we combined the two methods to distinguish
      the images by a rule-based method, 67.1% of wrongly identified patients in our
      database could be identified as wrongly identified, without any false warnings
      for correctly identified patients. We consider that this automated method for
      patient recognition based on edge-enhanced images would be useful in preventing
      "wrong" images from being stored in a PACS environment.

PMID- 14646996
TI  - [New evaluation for osteoporosis using calcaneal computed radiographs].
AB  - Quantitative analysis of bone mass is a method mainly used for the diagnosis of
      osteoporosis. However, there are cases of osteoporosis that cannot be diagnosed
      by this method alone. This study was performed to develop a new quantitative
      method for the evaluation of osteoporosis using texture analysis and geometric
      feature analysis of trabecular bone on lateral calcaneal computed radiographs.
      Thirty-seven cases including 11 normal and 26 abnormal lateral calcaneal
      radiographs were examined. The patients' ages ranged from 24 to 89 years (average
      age, 58.3 years). The root mean square (RMS) variation and first moment of power
      spectrum of trabecular bone patterns were determined as quantitative measures for
      texture analysis. In addition, the total area and total length of trabecular bone
      were obtained from geometric feature analysis. The RMS variations in pixel
      values, total area, and total length of trabecular bone were decreased as bone
      atrophy progressed. These three quantitative measures corresponded well to
      radiologists' subjective evaluations of bone atrophy. Moreover, our results
      indicated that these three quantitative measures had strong correlations with
      bone mineral density of the femoral neck. Therefore, we consider the computerized
      method with texture analysis and geometric feature analysis of lateral calcaneal
      radiographs to be very useful for radiologists in evaluating osteoporosis.

PMID- 14646997
TI  - [Verification of the portal skin mark for radiotherapy].
AB  - Verification of portal skin mark in radiotherapy is very important for external
      beam therapy because precision in radiotherapy depends on accuracy of the skin
      marking throughout the course of radiotherapy. In taking steps to preserve the
      skin mark, an adhesive tape and plastic bandage material spray are used on the
      mark after skin is marked with an oil based marking pen, and skin marking
      materials on the market are used as well. We compared the methods of preserving
      the skin mark. The results are (1) it was effective to remove oil from skin
      before marking. (2) the adhesive tape and the plastic bandage material spray were
      useful for skin marking drawn with an oil based marking pen. (3) the skin marking
      materials on the market were useful as well. (4) it is necessary to use properly
      the skin marking materials depending on the condition of skin. Most of all, it is
      essential to inform patients on the importance of skin marking in clinical
      radiotherapy.

PMID- 14646998
TI  - [Gastric phantom for training beginners in gastric segment (Stomap) recognition].
AB  - It is usually difficult for a beginner to understand precisely and quickly the
      three-dimensional (3D) construction of gastric lesions in a gastric X-ray
      examination with barium meal. In this study, a training-use stomach phantom was
      developed using the stomach segment to provide beginners with an understanding of
      3D stomach construction. The hook-shaped phantom (the shape of the stomach when a
      patient is in the supine position) was formed by using styrene, wire, and clay.
      It was then coated with dental stiffening agent, and wires were attached along
      the stomach segment. After drying, the stomach phantom was cut off and the oil
      clay was removed. The phantom then was immersed in water and the oil clay was
      dried. After that, the phantom again was glued together with a dental stiffening
      agent. The usefulness of the phantom was determined by an evaluation experiment.
      Ten students, as observers, were selected randomly for evaluation from 40
      students of the Department of Radiological Technology, College of Medical
      Technology, Hokkaido University. Eight films were shown to the observers, 4 films
      with segment and 4 films without segment. The observers checked 5 markers in
      different positions of the phantom and recorded the results on an answer sheet
      with segment picture. The significance of position recognition was identified by
      Wilcoxon's sign rank sum test (p=0.021) between the segment film and non-segment
      film.

PMID- 14646999
TI  - Neuroendocrine and cytokines-induced responses to minutes, hours, and days of
      mental stress.
AB  - OBJECTIVES: Previously, a large number of studies reported that psychological
      stress and psychiatric illness reduces immune responsiveness. However, it turned
      out that stress reduces immune responsiveness is an oversimplified statement
      because the interactions between central nervous system, endocrine system and the
      immune system are undoubtedly complex. Therefore, this study aims in reviewing
      mental stress models (e.g. brief and written examination stress as subacute and
      acute type of stressor) that have been utilized to understand the effect of
      stress on the neuroendocrine and immune systems. METHODS: The published findings
      from human mental stress models on catecholamines, cortisol, prolactin levels and
      on T helper (Th) 1 and 2-induced cytokines are presented and discussed with
      respect to the in vitro and in vivo effects of glucocorticoids, catecholamines,
      and prolactin on the induction of cytokines. RESULTS: This review shows evidence
      that short-time (minutes) or preparation to a written examination, in those
      students who are stressed, induces the production of proinflammatory cytokines
      which may be related to Th1 response. However, longer mental stress (days) causes
      dysregulation in the immune function by shifting the cytokine response to Th2
      response. CONCLUSIONS: The outcome from neuroendocrine and immune function prior
      to, following and after mental stress depends on multiple variables most
      importantly on the amount of stress, exposure time, coping behavior and
      adjustment of the individual. A few minutes of stress may improve immune
      performance but longer times of mental stress have detrimental effects that may
      lead to loss of immune integrity. Furthermore, studies on stress and common heath
      problems are necessary to increase our knowledge and understanding of the
      mechanisms responsible for producing neuroendocrine-induced immune changes in
      health and common diseases.

PMID- 14647000
TI  - The role of oxidative stress in physiological and pathological processes in the
      thyroid gland; possible involvement in pineal-thyroid interactions.
AB  - Reactive oxygen species (ROS) play an important role in physiological processes,
      but - when being in excess - ROS cause oxidative damage to molecules. Under
      physiological conditions, the production and detoxification of ROS are more-or
      less balanced. Also in the thyroid, ROS and free radicals participate in
      physiological and pathological processes in the gland. For example, hydrogen
      peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different
      steps of the process. Additionally, H2O2 is believed to participate in the Wolff
      Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much
      evidence has been accumulated indicating that oxidative stress is involved in
      pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or
      thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory
      product of the pineal gland - is a well-known antioxidant and free radical
      scavenger, widely distributed in the organism. Mutual relationships between the
      pineal gland and the thyroid have - for a long time - been a subject of intensive
      research. The abundant to-date's evidence relates mostly to the inhibitory action
      of melatonin on the thyroid growth and function and - to a lesser extent - to the
      stimulatory effects of thyroid hormones on the pineal gland. It is highly
      probable that under physiological conditions melatonin and, possibly, other
      antioxidants regulate ROS generation for thyroid hormone synthesis. We believe
      that melatonin may protect against extensive oxidative damage in the course of
      certain thyroid disorders or in case of a harmful action of some external factors
      on the thyroid. Thus, oxidative damage and the protective action of antioxidants,
      melatonin included, may occur during both physiological and pathological
      processes in the thyroid, however, this assumption, requires further studies.

PMID- 14647001
TI  - Free radicals after painful stimulation are influenced by antioxidants and
      analgesics.
AB  - OBJECTIVES: To study the balance between the pro-oxidative and antioxidative
      defence system after repeated painful stimulation in rats and the efficacy of the
      administration of different antioxidants (vitamins C, E, A, and selenium),
      analgesics (acetylsalicylic acid, morphine), and their combinations. METHODS:
      Mechanical clamping of both hind limbs was applied for 10 min for 5 consecutive
      days in adult male Wistar rats. The tail-flick latency was measured before and
      after a 5-day nociceptive stimulation with or without the substance application.
      The reactive oxygen species (ROS) were determined in the sensorimotor cortex.
      RESULTS: Painful stimulation increased lipoperoxidation which persisted for up to
      15 days after it had been discontinued. A simultaneous injection of antioxidants
      decreased the levels of TBARS, SOD and GSHPx; however, antioxidants applied one
      week prior to the painful stimulation were ineffective. A simultaneous injection
      of analgesics reduced stress-induced analgesia caused by the nociceptive
      stimulation, but did not affect lipoperoxidation. CONCLUSIONS: A combination of
      antioxidants with analgesics normalized both the oxidative stress and functional
      (the tail-flick latency) indicators. These results suggest that the
      administration of antioxidants in pain treatment may be employed to decrease the
      doses of analgesics and to prevent the negative impact of reactive oxygen species
      on nociception.

PMID- 14647002
TI  - Melatonin does not affect p21 expression in rat thyroid follicular cells.
AB  - OBJECTIVES: The cell-cycle (cc) is, in part, controlled by cyclin-dependent
      kinases (CDKs), which are activated after binding cyclins (positive regulators of
      cc). CDK inhibitors (CDKIs), such as p15, p16, p21, and p27, inhibit cyclin-CDK
      complex activity, and function as negative cell cycle regulators, blocking cell
      cycle progression. The aim of our study was to examine the influence of late
      afternoon (1600-1800) subcutaneous (s.c.) melatonin (Mel) injections,
      administered for 2 weeks, on the p21 expression in male Wistar rat thyroid
      follicular cells (TFC). METHODS: In order to detect the anti-p21 antibodies, the
      DAKO LSAB2 Rat Kit/HRP (DAKO, USA) and DAKO Liquid DAB Substrate-Chromogen System
      (DAKO, USA) were employed. RESULTS: No statistically significant changes of
      p21(LI) (p21 labelling index) values were observed in particular groups of the
      rats receiving Mel injections, in comparison to the controls. The statistical
      difference of p21(LI) values (p<0.03) was only observed between groups of rats,
      receiving Mel injections in the dose of 25 microg/daily and 100 microg/daily.
      CONCLUSION: Melatonin - in the applied doses and in the experimental conditions
      without any factors revealing anti-DNA activity - did not change, in any
      statistical way, p21 expression in rat thyroid follicular cells, as compared to
      the control group.

PMID- 14647003
TI  - Effect of unilateral superior cervical ganglionectomy on mandibular bone in rats.
AB  - OBJECTIVE: To assess the effect of local sympathectomy on mandibular bone during
      tooth eruption in rats. METHODS: The effect of a unilateral superior cervical
      ganglionectomy (Gx) on morphometry of ipsi- and contralateral mandible and
      volumetric bone density (as assessed by peripheral computed tomography) was
      examined 30 days after surgery. RESULTS: Only a few mandibular morphometric
      parameters decreased significantly after denervation in rats subjected to a
      unilateral Gx and a contralateral sham-operation. Mandibular volumetric bone
      density decreased significantly after sympathetic denervation. In a second
      experiment, carried out under conditions of unilateral unimpeded eruption of
      incisors performed ipsilaterally or contralaterally to a unilateral Gx, a
      significant interaction "denervation x type of eruption" was found for most
      morphometric parameters. Further analysis indicated higher morphometric indexes
      in denervated mandibles than in the innervated ones under impeded incisor
      eruption conditions, and lower morphometric indexes in denervated mandibles than
      in the innervated ones under unimpeded incisor eruption conditions. Unimpeded
      eruption augmented total volumetric bone density providing the innervation was
      intact and caused opposite effects on cortical volumetric bone density in the
      presence of innervation (increase) or absence of innervation (decrease).
      Trabecular volumetric bone density decreased significantly after sympathetic
      denervation. CONCLUSION: The results support a role of the sympathetic nervous
      system in the regulation of bone remodeling.

PMID- 14647004
TI  - Serum testosterone levels and coital activity in men with somatosexual disorders.
AB  - OBJECTIVES: The aim of our study is to assess the relationship between serum
      testosterone levels and the coital activity in groups of married men with
      Klinefelter's syndrome and in men with a varicocele investigated for marital
      infertility. These are compared with a group of somatosexually well developed men
      with a normozoospermia and adequate sexual life. SUBJECT AND METHODS: The serum
      testosterone levels were assessed in 77 patients with Klinefelter's syndrome
      (mean age 31 years, SD 5.78), 58 men with a varicocele (mean age 30.5 years, SD
      5.80) and 85 healthy men with normal spermiological values (mean age 32.7 years,
      SD 6.31). The frequency of sexual intercourse in their marriage was assessed by
      interview. RESULTS: We found that, although their serum testosterone levels were
      significantly lower (p < 0.01), the coital activity in both groups with
      somatosexual disorders did not significantly differ from the group of men with
      normal semen parameters. The coital activity in the group of men with
      Klinefelter's syndrome decreased after 35 years of age, before any decrease in
      serum male sex hormone levels occurred. CONCLUSION: Statistical analysis revealed
      that coital activity did not correlate with testosterone levels, but correlated
      significantly with age. A possible interpretation of the data is that Mother
      Nature ensues the survival of species by the production of not only a redundant
      amount of spermatozoids, but also of male sex hormones.

PMID- 14647005
TI  - Associations between the human insulin gene 5' VNTR and clinical variables of the
      renin-angiotensin system.
AB  - BACKGROUND: Blood pressure regulation is a complex process influenced by numerous
      environmental and genetic factors. Consequently, there's no cookie-cutter
      approach for the elucidation of of the genetic mechanism involved. One of the
      goals of molecular geneticists in the field of hypertension is to unravel the
      genetic architecture of blood pressure regulation. METHODS: With the aim of
      identifying quantitative trait loci participating in the control of blood
      pressure, we carried out a pilot study on a sample population of middle-aged,
      U.S. Caucasians (44 subjects). The design of the study was to search for
      associations between clinical variables of blood pressure regulation pertaining
      to the renin-angiotensin-aldosterone system (systolic and diastolic blood
      pressures, urinary excretion of sodium, potassium and aldosterone, plasma renin
      activity) and a genetic marker at a candidate gene locus - the human insulin gene
      (INS) RESULTS: We observed significant associations between a variable number of
      tandem repeats (VNTR) marker (visualized as a biallelic, class I/class III marker
      system) localized at the 5' end of the human INS gene, and plasma renin activity
      and urinary sodium, potassium and aldosterone. CONCLUSION: Our results indicate
      that between 6 and 10 QTLs with comparable effects could be involved in blood
      pressure regulation via the rennin angiotensin system.

PMID- 14647006
TI  - Peptide Epitalon activates chromatin at the old age.
AB  - OBJECTIVES and design. We have studied the effect of synthetic peptide Epitalon
      on the activity of ribosomal genes, denaturation parameters of total
      heterochromatin, polymorphism of structural C-heterochromatin and the variability
      of facultative heterochromatin in cultured lymphocytes of persons aged 76-80
      years. RESULTS: The obtained data demonstrate that Epitalon induces the
      activation of ribosomal genes, decondensation of pericentromeric structural
      heterochromatin and the release of genes repressed due to the age-related
      condensation of euchromatic chromosome regions. CONCLUSIONS: Epitalon has shown
      its ability to activate chromatin by modifying heterochromatin and
      heterochromatinized chromosome regions in the cells of older persons.

PMID- 14647007
TI  - Effects of treatment with somatostatin analogues on the occurrence of apoptosis
      in somatotropinomas.
AB  - OBJECTIVES: Apoptosis of endocrine cells represents one of factors significantly
      affected the control of hormones secretion. Present study aimed to examine
      whether treatment of somatotropinoma types tumours with somatostatine analogue
      (lanreotide) results in apoptosis. MATERIAL AND METHODS: The studies were
      performed on 35 patients with somatotropinoma type tumours on whom adenomectomy
      was performed by transsphenoidal approach. The operative material was examined by
      cellular morphology, based on light and electron microscopy and chromosomal
      ladder formation assay. RESULTS: The number of apoptotic cells showed features
      typical for the process as condensation and fragmentation of chromatin,
      vacuolisation, damage of the inner structure of mitochondria and oligonucleosomal
      fragmentation of DNA was found in the study material. The results of the studies
      demonstrated the occurrence of lanreotide induced apoptosis in somatotropinoma
      type tumours. The grade of apoptotic cells in macroadenomas type adenomas,
      treated with lanreotide, ranged from 4.0% to 17.1% (mean 8.7+/-2.6%). Patients in
      whom hypophysectomy was not preceded by lanreotide treatment demonstrated low
      level of apoptotic cells (no more than 3.5%). CONCLUSIONS: The studies showed
      that treatment with somatostatine analogue-lanreotide induced apoptosis of tumour
      cell suggesting that the induction of apoptotic cell death may be involved in the
      anticancer activity of somatostatine analogue.

PMID- 14647008
TI  - Thousands of blood pressure and heart rate measurements at fixed clock hours may
      mislead.
AB  - The diagnoses of summer or winter hypertension in one and the same person can
      depend upon the clock hour of measurement.

PMID- 14647009
TI  - In vitro effect of melatonin on oxygen consumption in liver mitochondria of rats.
AB  - OBJECTIVE: To examine the in vitro effect of melatonin on rat mitochondrial liver
      respiration. METHODS: Oxygen consumption by liver mitochondria was measured
      polarographically in the presence of one of the following Krebs' cycle
      substrates: Lsuccinate, DL-3- beta-hydroxybutyrate or L-malate. Respiratory
      velocities at rest (state 4) and during rapid respiration in the presence of
      substrate and adenosine diphosphate (state 3) were measured in the presence of 10
      (-9)-10(-3) M concentrations of melatonin. RESULTS: In vitro melatonin (10(-7)
      10(-3) M) reduced state 3 mitochondrial respiration. Basal, state 4 respiration
      was not affected by melatonin. Consequently, control respiratory index (i.e., the
      ratio of state 3 to state 4 respiration) was inhibited by melatonin with a
      threshold at 10(-7) M concentration. CONCLUSION: The ability of melatonin to
      curtail acutely the stimulation of oxygen consumption in liver mitochondria may
      protect the mitochondria from excessive oxidative damage.

PMID- 14647010
TI  - The effect of intraperitoneal melatonin supplementation on the release of thyroid
      hormones and testosterone in rats with hyperthyroid.
AB  - OBJECTIVE: Melatonin has a general inhibitory effect on the reproductive system
      and thyroid functions. Testosterone secretion increases in parallel to thyroid
      hormones in hyperthyroidism. The aim of this study was to investigate the effects
      of melatonin application on total T3, T4 and testosterone in hyperthyroid rats.
      METHODS: This study was performed on 4 groups each consisted of 6 male Spraque
      Dawley rats. Control group (G1); sham group (G2); applied 0.5 ml/day of serum
      physiologic intraperitoneally for 2 weeks, hyperthyroid group (G3); applied 0.3
      mg/kg/day thyroxine intraperitoneally for 2 weeks, and hyperthyroid and melatonin
      supplemented group (G4); applied 0.3 mg/kg/day thyroxine and 3 mg/kg/day
      melatonin. Blood samples taken by way of decapitation were analysed for total T3,
      T4 and testosterone by RIA. RESULTS: Serum total T3 and total testosterone levels
      were the highest in hyperthyroid group (G3), whereas in hyperthyroid and
      melatonin supplemented group (G4) were the lowest (P<0.001). Total T4 levels were
      higher in group 3 than group 1, 2 and 4 (P<0.001). CONCLUSION: Results revealed
      that melatonin supplementation in hyperthyroidism suppress secretion of thyroid
      hormones and testosterone secretion.

PMID- 14647011
TI  - Plasma amino acids in ecstasy users.
AB  - Recreational use of the illegal drug "ecstasy" has increased dramatically in
      recent years. We have measured 33 different plasma amino acids in ecstasy users
      and controls. Significant differences were found for phosphoserine, glutamate,
      citrulline, methionine, tyrosine and histidine. Resembling changes in the plasma
      amino acids have been described in acute transient polymorphous psychosis. Thus,
      alterations in plasma - methionine and phosphoserine or other amino acids could
      be involved in the psychical symptoms produced by MDMA.

PMID- 14647012
TI  - Effects of melatonin and oxytetracycline in autologous intraperitoneal ovary
      transplantation in rats.
AB  - OBJECTIVES: To comparatively investigate the effects melatonin and
      oxytetracycline as antioxidants on autologous intraperitoneal ovary
      transplantation in rats. SETTING AND DESIGN: 28 adult female Wistar rats with
      regular estrous cycles were randomly divided into four groups. Group 1 (n=7) was
      the control group; Group 2 (n=7) bilateral oophorectomy and intraperitoneal
      transplantation group; and Groups 3 (n=7) and 4 (n=7) firstly received 20
      mg/kg/IP melatonin and 10 mg/kg/IP oxytetracycline., respectively and fifteen
      minutes after that, they had bilateral oophorectomy and intraperitoneal
      transplantation. Ovarian tissue and blood malondialdehyde (MDA) levels,
      superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) levels were
      determined. Vaginal cytology and ovarian necrosis were histopathologically
      investigated. Kruskall Wallis analysis of variance was used in the statistical
      analysis of data. RESULTS: Ovarian necrosis, tissue MDA and plasma MDA levels
      were significantly higher in Group 2 compared to the Groups 1, 3 and 4 (p<0.03).
      SOD and GSHPx levels were significantly lower in group 2 compared to the groups
      1, 3 and 4 (p<0.03). Melatonin was found to be more effective on ovarian necrosis
      and tissue MDA level than the use of oxytetracycline following autologous
      intraperitoneal ovary transplantation (p<0.03). There was a significant positive
      correlation between tissue MDA level and ovarian necrosis and a very strong
      negative correlation between tissue MDA and SOD level (rs = +/-0.9, n=28,
      p=0.000). CONCLUSION: Although both melatonin and oxytetracycline were found to
      be effective in autologous intraperitoneal pelvic ovary transplantation,
      melatonin is more effective against both the ovarian necrosis and tissue MDA
      level in rats.

PMID- 14647013
TI  - Chronomics: imaging in time by phase synchronization reveals wide spectral
      biospheric resonances beyond short rhythms.

PMID- 14647014
TI  - Abortion surveillance--United States, 2000.
AB  - PROBLEM/CONDITION: CDC began abortion surveillance in 1969 to document the number
      and characteristics of women obtaining legal induced abortions. REPORTING PERIOD
      COVERED: This report summarizes and describes data reported to CDC regarding
      legal induced abortions obtained in the United States in 2000. DESCRIPTION OF
      SYSTEM: For each year since 1969, CDC has compiled abortion data by state or area
      of occurrence. During 1973-1997, data were received from or estimated for 52
      reporting areas in the United States: 50 states, the District of Columbia, and
      New York City. In 1998 and 1999, CDC compiled abortion data from 48 reporting
      areas. Alaska, California, New Hampshire, and Oklahoma did not report, and data
      for these areas were not estimated. In 2000, Oklahoma again reported these data,
      increasing the number of reporting areas to 49. RESULTS: A total of 857,475 legal
      induced abortions were reported to CDC for 2000 from 49 reporting areas,
      representing a 0.5% decrease from the 861,789 legal induced abortions reported by
      48 reporting areas for 1999 and a 1.3% decrease for the same 48 reporting areas
      that reported in 1999. The abortion ratio, defined as the number of abortions per
      1,000 live births, was 246 in 2000 (for the same 48 reporting areas as 1999),
      compared with 256 reported for 1999. This represents a 3.8% decline in the
      abortion ratio. The abortion rate (for the same 48 reporting areas as 1999) was
      16 per 1,000 women aged 15-44 years for 2000. This was also a 3.8% decrease from
      the rate reported for procedures performed during 1997-1999 for the same 48
      reporting areas. The highest percentages of reported abortions were for women
      aged <25 years (52%), women who were white (57%), and unmarried women (81%).
      Fifty-eight percent of all abortions for which gestational age was reported were
      performed at < or =8 weeks of gestation, and 88% were performed before 13 weeks.
      From 1992 (when detailed data regarding early abortions were first collected)
      through 2000, steady increases have occurred in the percentage of abortions
      performed at < or =6 weeks of gestation. Few abortions were performed after 15
      weeks of gestation; 4.3% were obtained at 16-20 weeks and 1.4% were obtained at >
      or =21 weeks. A total of 31 reporting areas submitted data stating that they
      performed medical (nonsurgical) procedures, making up 1.0% of all reported
      procedures from the 42 areas with adequate reporting on type of procedure. In
      1998 and 1999 (the most recent years for which data are available), 14 women died
      as a result of complications from known legal induced abortion. Ten of these
      deaths occurred in 1998 and four occurred in 1999; no deaths were associated with
      known illegal abortion. INTERPRETATION: From 1990 through 1997, the number of
      legal induced abortions gradually declined. In 1998 and 1999, the number of
      abortions continued to decrease when comparing the same 48 reporting areas. In
      2000, even with one additional reporting state, the number of abortions declined
      slightly. In 1998 and 1999, as in previous years, deaths related to legal induced
      abortions occurred rarely (<1 death per 100,000 abortions). PUBLIC HEALTH ACTION:
      Abortion surveillance in the United States continues to provide data necessary
      for examining trends in numbers and characteristics of women who obtain legal
      induced abortions and for increasing understanding of one additional aspect of
      the spectrum of pregnancy outcomes. Policy makers and program planners need these
      data to improve the health and well-being of women and infants.

PMID- 14647015
TI  - Increases in HIV diagnoses--29 States, 1999-2002.
AB  - Since the advent of highly active antiretroviral therapy (HAART) in 1996,
      progression from receiving diagnosis of human immunodeficiency virus (HIV)
      infection to having acquired immunodeficiency syndrome (AIDS) has slowed
      substantially, making HIV-transmission patterns less predictable through AIDS
      surveillance alone. Consequently, CDC has recommended that states report
      diagnoses of HIV infections in addition to cases of AIDS. Recent estimates of HIV
      diagnoses suggested a leveling of the downward trend in HIV infections nationally
      and increases in HIV infections among certain populations. Reports of syphilis
      outbreaks and increased unprotected sex raised concerns regarding increases in
      HIV transmission among men who have sex with men (MSM). In response to these
      developments, CDC analyzed trends in HIV diagnoses in 29 states that conducted
      name-based HIV/AIDS surveillance during 1999-2002. This report summarizes the
      results of that study, which indicated that HIV diagnoses increased among men,
      particularly MSM, and also among non-Hispanic whites and Hispanics. The findings
      emphasize the need for new prevention strategies to reverse potential increases
      in HIV transmission among these populations.

PMID- 14647016
TI  - Health status of American Indians compared with other racial/ethnic minority
      populations--selected states, 2001-2002.
AB  - Despite overall declines in morbidity and mortality in the United States in
      recent years, a persistent gap in health status remains between American Indians
      (AIs) and non-Hispanic whites. This report compares the health status of AIs with
      that of other racial/ethnic minority populations by using data from a survey
      conducted during 2001-2002 in 21 communities through the Racial and Ethnic
      Approaches to Community Health (REACH) 2010 project. The results indicate that
      although AIs had a higher prevalence of chronic disease risk factors than other
      racial/ethnic minority populations, they also were more likely to use preventive
      services. Culturally sensitive primary prevention strategies to reduce risk
      factors and disease burden in AI communities should be developed and implemented.

PMID- 14647017
TI  - Diabetes among Hispanics--Los Angeles County, California, 2002-2003.
AB  - Diabetes is associated with severe morbidity and premature death and affects U.S.
      Hispanics disproportionately. Although regional variation in diabetes prevalence
      has been observed among Hispanics, limited information is available on how
      sociodemographic factors affect the risk for diabetes among Hispanics in urban
      settings. Los Angeles County (LAC), California, has the largest urban Hispanic
      population in the United States. To assess the prevalence of diabetes among
      Hispanic adults in LAC and to examine variations in diabetes prevalence across
      sociodemographic groups in this population, the LAC Department of Health Services
      analyzed data from the 2002-2003 LAC Health Survey (LACHS). This report
      summarizes the results of that analysis, which indicate that the prevalence of
      diabetes is approximately two times higher among Hispanics than among non
      Hispanic whites and is strongly associated with living below poverty level. These
      findings underscore the need to provide additional diabetes prevention and
      treatment interventions for Hispanics in LAC, particularly those living in
      poverty.

PMID- 14647018
TI  - Hepatitis A outbreak associated with green onions at a restaurant--Monaca,
      Pennsylvania, 2003.
AB  - The Pennsylvania Department of Health and CDC are investigating an outbreak of
      hepatitis A outbreak among patrons of a restaurant (Restaurant A) in Monaca,
      Pennsylvania. As of November 20, approximately 555 persons with hepatitis A have
      been identified, including at least 13 Restaurant A food service workers and 75
      residents of six other states who dined at Restaurant A. Three persons have died.
      Preliminary sequence analysis of a 340 nucleotide region of viral RNA obtained
      from three patrons who had hepatitis A indicated that all three virus sequences
      were identical. Preliminary analysis of a case-control study implicated green
      onions as the source of the outbreak.

PMID- 14647019
TI  - Global progress toward certifying polio eradication and laboratory containment of
      wild polioviruses--August 2002-August 2003.
AB  - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, the
      number of countries in which polio is endemic has declined from 125 to seven.
      These countries are in three of the six World Health Organization (WHO) regions
      (i.e., African, Eastern Mediterranean, and South East Asian). The other three
      regions (i.e., Americas, European, and Western Pacific) were certified previously
      as polio-free. This report summarizes the progress made toward global
      certification of poliomyelitis eradication and implementation of measures to
      ensure laboratory containment of wild polioviruses (WPVs). The findings indicate
      that, although much progress has been made, wide disparities in certification and
      laboratory-containment capabilities underscore the need for continued efforts to
      verify the eradication of polio worldwide.

PMID- 14647020
TI  - West Nile virus activity--United States, November 20-25, 2003.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET as of 3 a.m., Mountain Standard Time, November 25, 2003.

PMID- 14647026
TI  - Surgical site infections: a cause for concern.

PMID- 14647027
TI  - Staphylococcus aureus nasal carriage and surgical-site infections.
AB  - The current literature indicates that surgical-site infections significantly
      increase costs and length of stay. Nosocomial infections that are acquired after
      operative procedures increase mortality rates. Staphylococcus aureus is a major
      cause of surgical-site infections among patients, particularly patients who
      undergo cardiothoracic surgery. Patients who carry S aureus in their nares are at
      increased risk for surgical-site infections that are caused by this organism.
      Occasionally, health care workers who carry S aureus in their nares can cause
      outbreaks of surgical-site infections or other nosocomial infections. Persons who
      carry S aureus in their nares and have upper respiratory tract infections may
      spread this organism to numerous staff members and patients. Key measures for
      decreasing rates of these and other nosocomial infections include the appropriate
      use of prophylactic antimicrobial agents, surveillance and reporting of
      infections, and surveillance for clusters of infection caused by the same strain
      of S aureus and culture and surveys, when appropriate, to help identify infected
      health care workers. Additionally, surgical masks may prevent health care workers
      from inadvertent transmission of S aureus from their nares to patients' surgical
      sites.

PMID- 14647028
TI  - Prevention of Staphylococcus aureus infections among surgical patients: beyond
      traditional perioperative prophylaxis.
AB  - BACKGROUND: Health care-related infections cause significant patient morbidity
      and mortality rates and add excess costs that frequently are not reimbursed.
      Staphylococcus aureus has long been recognized as an important pathogen in human
      disease and is the most common cause of nosocomial infections. METHOD: The
      objective of this review of the English language literature and a MEDLINE search
      was to describe recent advances in the prevention of S aureus health care-related
      infections that are attributable to patients' endogenous colonization. The
      ecologic niche of S aureus is the anterior nares and nasal carriage increases the
      risk of the development of a surgical-site, lower respiratory tract, or
      bloodstream infection. S aureus carriers have a 2- to 9-fold increased risk of
      the development of a surgical-site or intravenous catheter infection. RESULTS:
      Three treatment strategies may eliminate nasal carriage: locally applied
      antibiotics or disinfectants, systemic antibiotics, and bacterial interference.
      Among these strategies, locally applied or systemic antibiotics are used most
      commonly. Nasal ointments or sprays and oral antibiotics have variable efficacy,
      and their use frequently results in antimicrobial resistance among S aureus
      strains. Of the commonly used agents, mupirocin (pseudomonic acid) ointment has
      been shown to be 97% effective in reducing S aureus nasal carriage. In a recently
      published randomized, double-blind, placebo-controlled trial to determine whether
      intranasal mupirocin reduced the rate of S aureus-infected surgical-site and
      other S aureus health care-related infections; 4% of S aureus nasal carriers who
      received mupirocin acquired S aureus health care-related infections compared with
      7.7% of S aureus nasal carriers who received placebo (P=.02). The S aureus
      surgical-site infection rate was not reduced significantly, but carriers who
      received mupirocin before cardiothoracic or general surgery operations had almost
      50% fewer S aureus surgical-site infections than carriers who received placebo.
      In this setting resistance rarely has been reported. CONCLUSIONS: Given the
      importance of S aureus nosocomial infections and the increased risk of S aureus
      nasal carriage in patients with health care-related infections, investigators
      must study cost-effective strategies to further prevent certain types of health
      care-related infections or nosocomial infections that occur in specific settings.
      One potential strategy is to decrease or eliminate S aureus nasal carriage among
      certain patient populations or in certain healthcare settings.

PMID- 14647029
TI  - Experience in prevention of sternal wound infections in nasal carriers of
      Staphylococcus aureus.
AB  - Nosocomial and surgical-site infections are significant burdens to the health
      care system that account for $5 billion and $1.6 billion each year in the United
      States, respectively. These infections are associated with significant morbidity
      and mortality rates, increased length of hospitalization, and increased treatment
      costs that are often not reimbursed by third-party payers. Approximately 40% of
      sternal wound infections in cardiac surgery patients are caused by Staphylococcus
      aureus and the prevalence of methicillin-resistant S aureus (MRSA) has risen
      dramatically in the past 2 to 3 decades. The economic burden that is associated
      with MRSA is significant; infections caused by MRSA cost approximately $3700 more
      to treat than infections caused by methicillin-sensitive S aureus, and the death
      rate for MRSA infection is nearly 3 times that of methicillin-sensitive S aureus.
      Thus, interventions to prevent nosocomial infection in patients who undergo
      cardiac surgery may improve outcomes and decrease costs. Advances in diagnostic
      testing may help to target intranasal antibiotic therapy to those patients who
      are most likely to receive a benefit. The LightCycler System is a fast and
      effective polymerase chain reaction-based diagnostic test that may be used to
      identify patients with nasal colonization of S aureus. Carrier status can be
      determined in a matter of hours rather than days as is the case with traditional
      culture techniques.

PMID- 14647031
TI  - Alcoholic liver disease: is it an "extraintestinal" complication of alcohol
      induced intestinal injury?

PMID- 14647032
TI  - Apoptosis and oxidants in the heart.
AB  - Cardiomyocyte (CM) apoptosis has been reported in a variety of cardiovascular
      diseases, including myocardial infarction, ischemia/reperfusion, end-stage heart
      failure, arrhythmogenic right ventricular dysplasia, and adriamycin-induced
      cardiomyopathy. The role of CM apoptosis in the development and progression of
      cardiac diseases merits further investigation. Cumulative evidence suggests that
      reactive oxygen species (ROS), which have been implicated in cardiac
      pathophysiology, can trigger myocyte apoptosis by up-regulating proapoptotic
      proteins, such as Bax and caspases, and the mitochondria-dependent pathway. These
      apoptotic proteins and pathways are inhibited by various antioxidants, as well as
      by overexpression of the antiapoptotic protein Bcl-2 by way of the antioxidant
      pathway. Detection of CM apoptosis with the terminal transferase-mediated DNA
      nick-end labeling assay alone has recently been questioned because of technical
      concerns regarding its sensitivity and specificity. Because CMs are mononuclear
      or binuclear, if only one nucleus or a certain percentage of fragmented nuclei is
      stained with TUNEL assay at the early stage of apoptotic cell death, it remains
      unknown whether this particular early apoptotic CM is still functionally active.
      The issue of TUNEL specificity further questions reports of high percentages of
      apoptotic CM nuclei (0.02%-35%) in the heart. Nevertheless, oxidative stress is a
      major apoptotic stimulus in many cardiovascular diseases and the process can be
      inhibited by antioxidants both in vitro and in vivo.

PMID- 14647033
TI  - Detection of conformational transformation of antithrombin in blood with crossed
      immunoelectrophoresis: new application for a classical method.
AB  - The structural flexibility of antithrombin is essential for its molecular
      trapping mechanism but also makes it vulnerable to even minor changes affecting
      its conformational stability, which influences hemostasis significantly. The
      conformational transformation of this serpin has been poorly investigated in
      biologic samples because available immunologic methods hardly differentiate
      between different conformations of this protein. Crossed immunoelectrophoresis
      (CIE) in presence of heparin has been classically used to identify mutant
      antithrombins with low heparin affinity. We demonstrate that this method also
      separates native and relaxed antithrombin, permitting the analysis of
      conformational variations of this potent anticoagulant with just a few
      microliters of plasma. However, CIE does not distinguish between antithrombin
      conformations with reduced heparin affinity: latent, cleaved, thrombin
      antithrombin complexes, or heparin-binding mutants. Therefore, clinical
      interpretation of CIE results should be examined with caution. Using this and
      other methods, and evaluating the functional activity of antithrombin, we
      analyzed the conformational transformation of antithrombin in biologic samples.
      We confirmed its transformation to the latent configuration by incubating it at
      50 degrees C. This conformational change also occurs at 37 degrees C, supporting
      the idea that this process is involved in the senescence of antithrombin.
      However, fresh plasma contains only traces of latent antithrombin, suggesting
      that this conformation is rapidly cleared in vivo. Finally, small increases in
      temperature (to 40 degrees C) resulted in a faster conformational transformation
      of antithrombin. Fever has been suggested to have key structural, functional, and
      clinical consequences in patients with conformational mutations in antithrombin.
      Our results support a role for small changes in temperature in nonmutated
      antithrombin, suggesting that fever is a general risk factor for thrombosis.

PMID- 14647034
TI  - Release of decay-accelerating factor into stools of patients with colorectal
      cancer by means of cleavage at the site of glycosylphosphatidylinositol anchor.
AB  - The expression of decay-accelerating factor (DAF), a cell-membrane-complement
      regulator, is enhanced in colorectal cancer, and DAF is detected in the stools of
      patients with colorectal cancer. In this study, to elucidate mechanisms whereby
      DAF is released into the colonic lumen, we analyzed and compared the properties
      of DAF in stools and colorectal-cancer tissues. Stool specimens taken before
      surgery and tissue samples from surgically resected colorectal cancers were
      obtained from 21 patients. We analyzed DAF in stool and tissue specimens using
      immunoblotting, ultracentrifugation, and phase separation with Triton X-114. We
      analyzed the expression profile of DAF mRNA in cancer tissues using reverse
      transcription-polymerase chain reaction to determine whether DAF transcripts for
      a secretory form of DAF were present. With the use of immunoblotting, stool DAF
      was detected as a broad band with a molecular weight of around 70,000 kDa that
      migrated slightly more slowly than cancer-tissue DAF. About 90% of stool DAF was
      present as a soluble form that remained in the 100,000 g supernatant after
      ultracentrifugation. On phase separation with Triton X-114, the soluble stool DAF
      was partitioned mainly into the aqueous phase, indicating its hydrophilic nature
      and lack of the fatty-acid glycosylphosphatidylinositol anchor component. In
      colorectal cancer tissues, reverse transcription-polymerase chain reaction
      experiments revealed a nonspliced DAF messenger RNA that encodes a secretory form
      of DAF in just 2 of the 21 specimens examined. These data suggest that DAF is
      released from colorectal cancer cells by way of cleavage of membrane-bound DAF at
      the site of the glycosylphosphatidylinositol anchor.

PMID- 14647035
TI  - Characterization of angiotensin II-receptor subtypes in podocytes.
AB  - Glomerular podocytes play a key role in maintaining the integrity of the
      glomerular filtration barrier. This function may be regulated by angiotensin II
      (Ang II) through activation of cell-surface receptors. Although studies suggest
      that podocytes express receptors for Ang II, the Ang II binding site has not been
      characterized with radioligand binding techniques. We therefore used iodine 125
      labeled Ang II to monitor Ang II-receptor density during differentiation of a
      mouse podocyte cell line. Scatchard analyses of equilibrium binding data revealed
      a single class of high-affinity binding sites (dissociation constant
      approximately 3 nmol/L) in both differentiated and nondifferentiated cells.
      During differentiation, the density of Ang II-receptor sites increased roughly 15
      fold in differentiated podocytes (maximal density of specific binding sites 881
      fmol/mg protein) compared with that in nondifferentiated cells (52 fmol/mg
      protein; P<.005). Glomerular podocytes expressed messenger RNA for AT1A, AT1B,
      and AT2 receptor subtypes, and competitive binding studies found that
      differentiated podocytes expressed mostly AT1 receptors (approximately 75%) with
      lesser amounts of AT2 (approximately 25%). Up-regulation of Ang II-receptor
      number was associated with increased Ang II-receptor responsiveness, as evidenced
      by enhanced Ang II-stimulated inositol phosphate (IP) generation and
      incorporation of tritiated thymidine. Both [3H]thymidine incorporation and IP
      generation were mediated by AT1-receptor activation. These data suggest that
      glomerular podocytes express a high-affinity binding site for Ang II with
      pharmacologic characteristics of both AT1 and AT2 receptors. This receptor site
      is up-regulated during podocyte differentiation, and receptor activation induces
      both IP generation and DNA synthesis by AT1-dependent mechanisms. We speculate
      that activation of podocyte Ang II receptors contributes to glomerular damage in
      disease states.

PMID- 14647036
TI  - Ethyl pyruvate ameliorates acute alcohol-induced liver injury and inflammation in
      mice.
AB  - Ethyl pyruvate dissolved in a calcium-containing balanced salt solution--Ringer's
      ethyl pyruvate solution (REPS)--ameliorates ileal mucosal hyperpermeability and
      decreases the expression of several proinflammatory genes when it is used instead
      of Ringer's lactate solution (RLS) to resuscitate mice from hemorrhagic shock.
      Herein, we sought to determine whether delayed treatment with REPS would be
      beneficial in a murine model of acute alcoholic liver injury associated with
      binge drinking. Mice were gavaged with 3 doses of ethanol (5 g/kg each dose) over
      a 12-hour period and then randomized to treatment with 3 intraperitoneal doses of
      REPS or RLS over 12 hours. Compared with sham-treated controls not subjected to
      alcohol intoxication, RLS-treated mice demonstrated histologic evidence of fatty
      change and piecemeal necrosis of hepatocytes in the liver, as well as a
      significant increase in the plasma concentration of alanine aminotransferase.
      Biochemical changes induced by alcohol administration included increased hepatic
      lipid peroxidation, nuclear factor-kappaB activation, and tumor necrosis factor
      alpha messenger RNA expression. All of these alcohol-induced effects were
      ameliorated by treatment with REPS instead of RLS. These data support the view
      that treatment with REPS ameliorates the hepatic inflammatory response and
      decreases hepatocellular injury in mice subjected to acute alcohol intoxication.

PMID- 14647037
TI  - Deferoxamine prevents cardiac hypertrophy and failure in the gerbil model of iron
      induced cardiomyopathy.
AB  - To evaluate the effects of the iron chelator deferoxamine on the functional and
      structural manifestations of iron-induced cardiac dysfunction, we measured
      cardiac power, left ventricular systolic, and diastolic function as (dP/dt)max
      and (dP/dt)min, respectively, and left ventricular and septal wall thickness in
      isolated heart preparations derived from the Mongolian gerbil model of iron
      overload. We induced iron overload with weekly subcutaneous injections of iron
      dextran (800 mg/kg/wk); deferoxamine (DFO; 100 mg/kg) was administered twice
      daily by subcutaneous injection, 5 of 7 days each week; and control animals
      received weekly subcutaneous injections of dextran alone. Animals administered
      iron alone initially exhibited, at 5 weeks, increased cardiac power but by 12 to
      20 weeks, cardiac power was severely diminished, with impairment of both systolic
      and diastolic function of the left ventricle and marked cardiac hypertrophy
      (P<.001 for all vs control animals). Administration of DFO with iron did not
      interfere with the initial augmentation of cardiac power at 5 weeks but prevented
      the subsequent deterioration in cardiac performance. After 12 to 20 weeks,
      gerbils given DFO with iron had mean values of cardiac power indistinguishable
      from those of control animals; both systolic and diastolic function were
      significantly enhanced not only in comparison with those of animals treated with
      iron alone but also with respect to controls. In addition, DFO prevented cardiac
      hypertrophy; mean ventricular and septal wall thickness in gerbils given DFO and
      iron were not significantly different from those in controls. In the gerbil model
      of iron overload, concurrent administration of DFO with iron prevents both the
      development of cardiac hypertrophy and the progressive deterioration in cardiac
      performance that are produced by chronic iron accumulation.

PMID- 14647038
TI  - Protection of mitochondrial perturbation by human T-lymphotropic virus type 1 tax
      through induction of Bcl-xL expression.
AB  - This study was designed to determine the inhibitory role of human T-lymphotropic
      virus type 1 (HTLV-1) tax against apoptotic cell death. We used JPX-9 cells, a
      Jurkat subclone generated by the stable introduction of a tax expression-plasmid
      vector, and induced tax expression in JPX-9 cells with CdCl2. Expression of Bcl
      2, Bcl-xL, and Bax in JPX-9 cells was assessed with Western blot analysis. Both
      tax-negative and tax-positive JPX-9 cells were incubated in the presence of
      several apoptogenic stimuli, and sensitivity to apoptogenic stimuli was also
      evaluated. Compared with tax-negative JPX-9 cells, Bcl-xL expression was clearly
      augmented in tax-positive JPX-9 cells. These cells were resistant to both
      receptor-mediated apoptosis (induced by anti-Fas IgM and tumor necrosis factor
      related apoptosis-inducing ligand) and chemical-induced apoptosis (induced by
      pyrrolidine dithiocarbamate, etoposide, and staurosporine), as evidenced by the
      presence of hypodiploid DNA-positive cells, activation of caspase-3 and caspase
      9, disruption of mitochondrial transmembrane potential (DeltaPsim) and inhibition
      of cytochrome c release in tax-positive JPX-9 cells compared with tax-negative
      JPX-9 cells. Our results suggest that tax-mediated Bcl-xL expression inhibits
      apoptosis of activated T-cells in HTLV-1-seropositive subjects, which
      consequently promotes the onset of autoimmune disorders such as Sjogren's
      syndrome.

PMID- 14647039
TI  - Calcifying epithelial odontogenic (Pindborg) tumor-associated amyloid consists of
      a novel human protein.
AB  - Calcifying epithelial odontogenic tumors (CEOTs), also known as Pindborg tumors,
      are characterized by the presence of squamous-cell proliferation, calcification,
      and, notably, amyloid deposits. On the basis of immunohistochemical analyses, the
      amyloidogenic component had heretofore been deemed to consist of cytokeratin
      related or other molecules; however, its chemical composition had never been
      elucidated. We have used our microanalytic techniques to characterize the protein
      nature of CEOT-associated amyloid isolated from specimens obtained from 3
      patients. As evidenced by the results of amino-acid sequencing and mass
      spectrometry, the fibrils were found to be composed of a polypeptide of
      approximately 46 mer. This component was identical in sequence to the N-terminal
      portion of a hypothetical 153-residue protein encoded by the FLJ20513 gene cloned
      from the human KATO III cell line. That the amyloid protein was derived from this
      larger molecule was demonstrated by reverse transcription-polymerase chain
      reaction amplification of tumor-cell RNA where a full-length FLJ20513 transcript
      was found. Furthermore, immunohistochemical analyses revealed that the amyloid
      within the CEOTs immunostained with antibodies prepared against a synthetic
      FLJ20513-related dodecapeptide. Our studies provide unequivocal evidence that
      CEOT-associated amyloid consists of a unique and previously undescribed protein
      that we provisionally designate APin.

PMID- 14647041
TI  - Action plan for liver disease research.

PMID- 14647040
TI  - Transcription factors in liver development, differentiation, and regeneration.

PMID- 14647042
TI  - Making the liver young again.

PMID- 14647043
TI  - Treatment of pre- and post-liver transplantation HBV infection: Should we aim at
      combination therapy?

PMID- 14647044
TI  - Liver biopsy size matters in chronic hepatitis: bigger is better.

PMID- 14647045
TI  - Chemokine systems and hepatitis C virus infection: is truth in the genes of the
      beholders?

PMID- 14647046
TI  - Early change in bilirubin levels is an important prognostic factor in severe
      alcoholic hepatitis treated with prednisolone.
AB  - Early identification of patients with severe (discriminant function >or=32)
      biopsy-proven alcoholic hepatitis (AH) who are not responding to corticosteroids
      would be clinically relevant. Our goal was to develop simple criteria that will
      help physicians to promptly identify nonresponders to corticosteroids. A total of
      238 patients were included. We used 6 months survival as an end point because of
      the rule requiring 6 months for listing alcoholic patients for transplantation.
      Overall survival at 1 and 6 months was 85% +/- 2.3% and 64.3% +/- 3.3%,
      respectively. An early change in bilirubin levels (ECBL) at 7 days (defined as
      bilirubin level at 7 days lower than bilirubin level on the first day of
      treatment) was observed in 73% of patients. At 7 days, in patients with ECBL,
      bilirubin decreased (84 +/- 75 micromol/L [4.94 +/- 4.40 mg/dL]), whereas it
      increased in patients without ECBL (76.5 +/- 77 micromol/L [4.50 +/- 4.54 mg/dL],
      P <.0001). Ninety-five percent of patients with ECBL continued to have improved
      liver function during treatment. At 6 months, survival of patients with ECBL was
      significantly higher than that of patients without ECBL, 82.8% +/- 3.3% versus
      23% +/- 5.8%, P <.0001. On multivariate analysis, ECBL, discriminant function and
      creatinine were independent prognostic variables, and ECBL had the most important
      prognostic value. In conclusion, ECBL is a very simple predictive factor for
      identifying nonresponders. A recommendation to discontinue corticosteroids after
      7 days in patients without ECBL, suggested by our results, awaits additional
      confirmation.

PMID- 14647047
TI  - Humoral and cardiac effects of TIPS in cirrhotic patients with different
      "effective" blood volume.
AB  - The aim of this study was to evaluate the cardiac effects of transjugular
      intrahepatic portosystemic shunts (TIPS) in cirrhotic patients with different
      effective blood volume. Two-dimensional echocardiography was performed before and
      7 and 28 days after TIPS insertion in 7 cirrhotic patients with PRA <4 ng/mL/h
      (group A, normal effective blood volume) and 15 with PRA >4 ng/mL/h (group B,
      reduced effective blood volume). Before TIPS, most cirrhotic patients showed
      diastolic dysfunction as indicated by reduced early maximal ventricular filling
      velocity (E)/late filling velocity (A) ratio. Patients of group B differed from
      patients of group A because of smaller left ventricular volumes and stroke
      volume, indicating central underfilling. After TIPS insertion, portal
      decompression was associated with a significant increase of cardiac output (CO)
      and a decrease of peripheral resistances. The most important changes were
      recorded in patients of group B, who showed a significant increase of both the
      end-diastolic left ventricular volumes and the E/A ratio and a significant
      decrease of PRA. In conclusion, these results show that the hemodynamic effects
      of TIPS differ according to the pre-TIPS effective blood volume. Furthermore,
      TIPS improves the diastolic cardiac function of cirrhotic patients with effective
      hypovolemia. This result is likely due to a TIPS-related improvement of the
      fullness of central blood volume.

PMID- 14647048
TI  - Effects of the V1a vasopressin agonist F-180 on portal hypertension-related
      bleeding in portal hypertensive rats.
AB  - F-180 is a new, long-acting analog of vasopressin with a selective agonist effect
      on the vascular V1a receptors, with the advantage of having no effect on renal V2
      receptors. F-180 is approximately 20 times more powerful than terlipressin in
      reducing portal pressure and has less marked systemic effects. The present study
      investigated the effects of F-180 on the outcome of portal hypertension-related
      bleeding in hypovolemic rats. Partial portal vein-ligated rats were subjected to
      portal hypertension-related bleeding by sectioning a first-order branch of the
      ileocolic vein. After hemodynamic stabilization, a second sectioning of the first
      order branch of the ileocolic vein section was performed in the already
      hypovolemic animals, and either F-180 or placebo was administered. Blood
      transfusion was adjusted to maintain mean arterial pressure (MAP) gamma > 80 mm
      Hg. The first section of a first-order branch of the ileocolic vein induced a
      hemorrhage of similar severity in both groups of rats. After a 2nd sectioning of
      a first-order branch of the ileocolic vein section, F-180 was more effective than
      placebo in recovering shock (MAP, 21% +/- 23% vs. 0% +/- 13% in placebo; P <.05),
      preventing portal pressure (PP) increase during blood transfusion (PP: -1% +/-
      19% vs. 47% +/- 65% in placebo; P =.07), reducing transfusion requirements (2.9
      +/- 3.3 mL vs. 11.2 +/- 6.0 mL in placebo; P <.01), diminishing the magnitude of
      collected blood losses (5.1 +/- 2.2 g vs. 12.7 +/-7.7 g in placebo; P <.05), and
      decreasing the mortality from the portal hypertension-related bleeding (10% vs.
      60% in placebo; P <.05). In conclusion, in hypovolemic portal-hypertensive rats
      during a portal hypertension-related bleeding, F-180 rapidly recovers arterial
      pressure and decreases transfusion requirements, blood losses, and mortality.

PMID- 14647049
TI  - Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for
      increased prevalence of type 2 diabetes.
AB  - Patients with hepatitis C virus (HCV) infection have a greater risk of developing
      type 2 diabetes mellitus. However, the mechanism of this association is unclear.
      In this study, we examined the potential defects in upstream insulin signaling
      pathways in liver specimens obtained from nonobese/nondiabetic subjects with HCV
      infection. Fasting liver biopsy specimens were obtained from 42 HCV-infected
      subjects and 10 non-HCV-infected subjects matched for age and body mass index.
      Liver tissues were exposed to insulin and examined for the contents and
      phosphorylation/activation status of the upstream insulin signaling molecules by
      immunoprecipitation and Western blot analysis. HCV infection resulted in a trend
      toward a 2-fold to 3-fold increase in insulin receptor (IR) and insulin receptor
      substrate (IRS)-1 contents when compared with non-HCV. In contrast, insulin
      stimulated IRS-1 tyrosine phosphorylation was decreased by 2-fold in HCV-infected
      subjects compared with non-HCV-infected subjects (P <.05). The observed
      reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold
      decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and
      a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs.
      non-HCV). This was accompanied by a marked reduction in insulin-stimulated Akt
      phosphorylation without any alterations in mitogen-activated protein kinase
      (MAPK) phosphorylation. Cellular contents of the hepatic p85 subunit of PI3
      kinase were comparable between HCV-infected and non-HCV-infected subjects. In
      conclusion, we found that (1). HCV infection leads to a postreceptor defect in
      IRS-1 association with the IR and (2). insulin signaling defects in hepatic IRS-1
      tyrosine phosphorylation and PI3-kinase association/activation may contribute to
      insulin resistance, which leads to the development of type 2 diabetes mellitus in
      patients with HCV infection.

PMID- 14647050
TI  - Role of reproductive factors in hepatocellular carcinoma: Impact on hepatitis B-
      and C-related risk.
AB  - Hepatocellular carcinoma (HCC) is more prevalent in men than in women. Estrogen
      may play some role in the development of HCC. We conducted a multicenter case
      control study to evaluate the effects of reproductive factors on HCC risk, and to
      assess whether the association between each factor and HCC differs between
      hepatitis B surface antigen (HBsAg)-positive and -negative women, in which
      hepatitis C virus (HCV) is the major cause of HCC. The study included 218 women
      with HCC and 729 control women selected from nonbiological and first-degree
      female relatives of patients with HCC. The risk of HCC was inversely related to
      the number of full-term pregnancies (FTP) (P(trend) =.0216) and age at natural
      menopause (P(trend) =.0251 among women aged 45-55 without prior surgical
      menopause). Oophorectomy at age <or=50 during premenopausal years was also a risk
      factor (multivariate-adjusted OR, 2.57; 95% CI, 1.42-4.63). Use of hormone
      replacement therapy (HRT) (multivariate-adjusted OR, 0.46; 95% CI, 0.27-0.79) was
      associated with a lower risk of HCC, and there was a trend in the risk with
      increasing duration of HRT (P(trend) = 0.0013). All reproductive factors had a
      similar impact on HBsAg-positive and -negative women except for an early menarche
      (<or=12 vs. >or=16 years), which increased HCC risk in HBsAg carriers
      (multivariate-adjusted OR, 6.96; 95% CI, 2.52-19.18) but posed no increased risk
      in noncarriers (P(interaction) =.0053). In conclusion, increased exposure to
      estrogen during adulthood may provide a protective effect against HCC.
      Nevertheless, an early menarche, which results in early estrogen exposure, does
      not confer protection for HBsAg carriers.

PMID- 14647051
TI  - Separate analysis of asialoglycoprotein receptors in the right and left hepatic
      lobes using Tc-GSA SPECT.
AB  - The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the sinusoidal
      surfaces of hepatocytes. We aimed to clarify the clinical significance of the
      regional distribution of ASGPRs in the human liver, especially in chronic viral
      hepatitis. Eighteen volunteers, 34 patients with chronic hepatitis, and 33
      patients with cirrhosis (11/Child-Pugh A, 11/Child-Pugh B, 11/Child-Pugh C) were
      studied using a newly developed, conventional technetium-99m
      diethylenetriaminepentaacetic acid-galactosyl human serum albumin ((99m)Tc-GSA),
      single photon emission computed tomography (SPECT) method. Using Cantlie's line
      as a guide, ASGPR dynamics were analyzed separately in the right and left lobes,
      as well as in the whole liver, using novel indices (the liver uptake ratio [LUR]
      and the liver uptake density [LUD], which reflect the amount and density of
      ASGPRs in the liver, respectively). Mean LUR and LUD values for the whole liver
      and the right and left lobes decreased with increasing progression of chronic
      viral hepatitis. The LUR for the whole liver correlated well with parameters
      measuring the hepatic functional reserve and the platelet count. The right LUR
      correlated particularly well with conventional liver function tests, and
      comparison of the right LUD with histologic findings showed that it was a good
      indicator of periportal and/or bridging necrosis and fibrosis. In conclusion, our
      (99m)Tc-GSA SPECT method was clinically useful in evaluating regional hepatic
      function and the progression of chronic viral hepatitis using dynamic changes in
      ASGPRs.

PMID- 14647052
TI  - Inhibitory effect of adefovir and lamivudine on the initiation of hepatitis B
      virus infection in primary tupaia hepatocytes.
AB  - Adefovir dipivoxil and lamivudine are two safe and efficacious drugs licensed for
      the treatment of chronic hepatitis B virus (HBV) infection. Both drugs inhibit
      the viral polymerase, resulting in a profound suppression of virus production.
      Blocking the viral polymerase may also affect the initiation of HBV infection,
      because HBV virions harbor a partially double-stranded genome and productive
      infection requires completion of viral plus-strand DNA synthesis with subsequent
      formation of covalently closed circular DNA (cccDNA). To address this issue, we
      used primary hepatocytes from the tree shrew Tupaia belangeri that were recently
      shown to be susceptible to HBV infection. Treatment of cells with either drug
      partially inhibited initial HBV cccDNA formation. Adefovir was more effective
      than lamivudine, resulting in a 3-fold reduction of RNA synthesis and viral
      surface antigen production. However, prevention of initial cccDNA formation was
      incomplete even after combined treatment, whereas de novo synthesis of viral
      replicative intermediates was completely suppressed. A possible explanation for
      this observation is the genomic plus-strand gap of less than 200 bases in some
      virions, limiting the window for antiviral action. In conclusion, nucleos(t)ide
      analogues can target initial plus-strand DNA repair and reduce but not completely
      block HBV infection.

PMID- 14647053
TI  - Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post
      liver transplantation patients.
AB  - Three-hundred and twenty-four patients were enrolled in an open-label,
      multicenter, international study in which pre- and post-liver transplantation
      (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine
      resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre-
      and post-LT cohorts, 128 and 196 patients were treated for a median duration of
      18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of
      treatment, 81% of the pre-LT and 34% of the post-LT cohort achieved undetectable
      serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor polymerase chain
      reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a
      median change in serum HBV DNA from baseline of -4.1 log(10) and -4.3 log(10)
      copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin,
      bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre-LT
      patients and 49%, 76%, 75%, and 20% of post-LT patients. The Child-Pugh-Turcotte
      (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis
      of 122 HBV baseline samples revealed that 98% of these patients had lamivudine
      resistant mutant HBV. No adefovir resistance mutations were identified in
      patients after 48 weeks of therapy. One-year survival was 84% for pre-LT and 93%
      for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects
      associated with adefovir dipivoxil in this setting were primarily mild to
      moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in
      significant improvements in virologic, biochemical, and clinical parameters in
      CHB patients pre- and post-LT with lamivudine-resistant HBV.

PMID- 14647054
TI  - Results of retransplantation for recurrent hepatitis C.
AB  - Retransplantation for recurrent hepatitis C virus (HCV) has been evaluated in
      small series. In this study, patients undergoing transplantation for HCV-related
      cirrhosis with subsequent retransplantation more than 90 days for recurrent HCV
      (proven by pathologic examination of the explant and exclusion of other factors)
      were prospectively followed. This group was compared with a simultaneous cohort
      without HCV infection undergoing retransplantation more than 90 days after
      primary transplantation. Forty-two patients underwent retransplantation for
      recurrent HCV with a median survival of 12.9 +/- 6.7 months after
      retransplantation. Twenty patients (48%) were dead at 6 months, and 13 (65%) of
      these deaths were due to sepsis. On univariate analysis, creatinine level greater
      than or equal to 3 mg/dL, platelet count less than 100000/microL, prothrombin
      time (PT) greater than or equal to 16 seconds, alkaline phosphatase level less
      than or equal to 240 U/L, gamma-glutamyltransferase level less than or equal to
      130 U/L, and donor age of 60 years or greater all correlated significantly with
      shorter survival after retransplantation. PT and donor age were predictors of
      survival on multivariate analysis. Patients undergoing retransplantation for
      recurrent HCV had a significantly shorter median survival than the 55 patients
      undergoing retransplantation for other chronic reasons of graft loss (75.6 +/-
      17.7 months). In conclusion, median survival after liver retransplantation for
      recurrent HCV is significantly shorter than after retransplantation for other
      causes of late graft loss. Most deaths occur in the first 6 months and are due to
      sepsis. Candidates for retransplantation with a preoperative PT less than 16
      seconds and those receiving grafts from donors younger than 60 years can expect a
      significantly longer median survival after retransplantation.

PMID- 14647055
TI  - Suppression of HCV-specific T cells without differential hierarchy demonstrated
      ex vivo in persistent HCV infection.
AB  - Hepatitis C virus (HCV) has a high propensity for persistence. To better define
      the immunologic determinants of HCV clearance and persistence, we examined the
      circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex
      vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361
      overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3
      NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific
      type-1 T-cell response was significantly greater in average frequency (0.24% vs.
      0.04% circulating lymphocytes, P =.001) and scope (14/36 vs. 4/36 pools, P =.002)
      among the recovered than the chronic subjects, and the T-cell response correlated
      inversely with HCV titer among the chronic subjects (R = -0.51, P =.049).
      Although highly antigenic regions were identified throughout the HCV genome,
      there was no apparent difference in the overall HCV-specific T-cell repertoire or
      type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was
      associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells
      and with higher frequency of CD4(+)CD25(+) regulatory T cells (7.3% chronic vs.
      2.5% recovered, P =.002) that could directly suppress HCV-specific type-1 CD8 T
      cells ex vivo. In conclusion, we found that HCV persistence is associated with a
      global quantitative and functional suppression of HCV-specific T cells but not
      differential antigenic hierarchy or cytokine phenotype relative to HCV clearance.
      The high frequency of CD4(+)CD25(+) regulatory T cells and their suppression of
      HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in
      HCV persistence.

PMID- 14647056
TI  - Sampling variability of liver fibrosis in chronic hepatitis C.
AB  - Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and
      liver biopsy remains the gold standard for fibrosis evaluation. However,
      variability in the distribution of fibrosis within the liver is a potential
      limitation. Our aim was to assess the heterogeneity of liver fibrosis and its
      influence on the accuracy of assessment of fibrosis with liver biopsy. Surgical
      samples of livers from patients with chronic hepatitis C were studied.
      Measurement of fibrosis was performed on the whole section by using both image
      analysis and METAVIR score (reference value). From the digitized image of the
      whole section, virtual biopsy specimens of increasing length were produced.
      Fibrosis was assessed independently on each individual virtual biopsy specimen.
      Results were compared with the reference value according to the length of the
      biopsy specimen. By using image analysis, the coefficient of variation of
      fibrosis measurement with 15-mm long biopsy specimens was 55%; and for biopsy
      specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of
      biopsies 15 mm in length were categorized correctly according to the reference
      value. This increased to 75% for a 25-mm liver biopsy specimen without any
      substantial benefit for longer biopsy specimens. Sampling variability of fibrosis
      is a significant limitation in the assessment of fibrosis with liver biopsy. In
      conclusion, this study suggests that a length of at least 25 mm is necessary to
      evaluate fibrosis accurately with a semiquantitative score. Sampling variability
      becomes a major limitation when using more accurate methods such as automated
      image analysis.

PMID- 14647057
TI  - Hepatitis C virus and liver disease: global transcriptional profiling and
      identification of potential markers.
AB  - Microarray analysis of RNA from hepatitis C virus (HCV)-infected cirrhotic livers
      was performed to identify a gene expression signature of liver disease. The
      expression levels of approximately 13600 genes were analyzed using surgical
      material and core biopsy specimens from HCV-infected cirrhotic liver explants in
      comparison with reference samples of normal nondiseased liver. In addition,
      normal liver samples were compared with each other to determine normal
      physiologic variation in gene expression. A set of genes, including some
      associated with stress, acute-phase immune response, and hepatic stellate cell
      activation, had variable expression levels in normal livers. These genes were
      subtracted from the sets of genes differentially expressed in cirrhotic livers.
      To exclude cancer-related genes from our marker sets, we subtracted genes that
      also were expressed differentially in hepatocellular carcinomas. The resultant
      HCV- and liver disease-associated gene set provided a molecular portrait of
      several processes occurring in the HCV-infected liver. It included (1). genes
      expressed in activated lymphocytes infiltrating the cirrhotic liver, and
      activated liver macrophages; (2). genes involved in remodeling of extracellular
      matrix-cell and cell-cell interactions associated with cytoskeleton
      rearrangements; (3). genes related to the anti-apoptotic pathway of Bcl-2
      signaling; and (4). genes involved with the interferon response and virus-host
      interactions. In conclusion, our microarray analysis identified several potential
      gene markers of HCV-associated liver disease and contributed to our rapidly
      expanding database of experiments describing HCV pathogenesis.

PMID- 14647058
TI  - Association of genetic variants of the chemokine receptor CCR5 and its ligands,
      RANTES and MCP-2, with outcome of HCV infection.
AB  - The effect of host genetic variation on the outcome of hepatitis C virus (HCV)
      infection and its treatment is poorly understood. The chemokine receptors CCR5,
      CCR2, and CCR3 and their ligands, RANTES, MCP-1, MCP-2, and MIP-1alpha, are
      involved in the immune responses and the selective recruitment of lymphocytes to
      the liver in HCV infection. We studied 20 polymorphisms within these genes and
      investigated their association with persistent carriage of HCV, severity of liver
      disease, hepatic inflammation, and response to treatment in a large European
      cohort. Significant associations were found between CCR5-delta32 and reduced
      portal inflammation (P =.011, odds ratio [OR]: 2.3, 95% confidence interval [CI]:
      1.09-4.84) and milder fibrosis (P =.015, OR: 1.97, 95% CI: 1.13-3.42). A promoter
      polymorphism at position -403 in the RANTES gene was associated with less severe
      portal inflammation (P =.004). An amino acid change in MCP2, Q46K, was associated
      with severity of fibrosis (P =.018, OR: 2.29, 95% CI: 1.14-4.58). In conclusion,
      our study suggests a possible role of the polymorphisms CCR5-delta32, RANTES 
      403, and MCP-2 Q46K in the outcome of HCV infection.

PMID- 14647059
TI  - Hepatic overexpression of caveolins increases bile salt secretion in mice.
AB  - Caveolins are cholesterol-binding proteins involved in the regulation of several
      intracellular processes, including cholesterol transport. Because hepatocytes
      express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid
      metabolism and biliary lipid secretion. Our aim was to investigate the potential
      physiologic role of caveolins in hepatic cholesterol and bile salt (BS)
      metabolism and transport using adenoviral gene transfer. C57BL/6 mice were
      infected with recombinant human caveolin-1 and caveolin-2 adenoviruses. Mice
      infected with adenovirus lacking the transgene were used as controls. Hepatic
      caveolin expression was evaluated by immunochemical methods. Reverse
      transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to
      assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium
      taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]).
      Serum, liver, biliary, and fecal biochemical determinations and BS maximal
      secretory rate (SRm) were performed by standard methods. Ad.Cav-1- and Ad.Cav-2
      infected mice exhibited a 10- and 7-fold increase in hepatic caveolin-1 and
      caveolin-2 protein expression, respectively. Caveolin-1-overexpressing mice had a
      significant increase in plasma high-density lipoprotein (HDL) cholesterol and
      hepatic free cholesterol content, whereas total plasma cholesterol and
      triglyceride levels remained unchanged. Hepatic caveolin-1 and/or caveolin-2
      overexpression significantly increased bile flow and secretion of all biliary
      lipids. Caveolin-1-overexpressing mice showed a 2.5-fold increase in taurocholate
      (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size
      and fecal BS excretion remained within the normal range in mice with Cav-1
      overexpression. No changes were seen in the protein mass of BS transporters Ntcp
      and Bsep. In conclusion, our findings indicate that caveolins may play an
      important role in regulating hepatic BS and cholesterol metabolism.

PMID- 14647060
TI  - Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P
      glycoprotein.
AB  - Intrahepatic cholestasis is often associated with impairment of biliary bile acid
      secretion, a process mediated by the sister of P-glycoprotein (Spgp or Abcb11)
      also known as the bile salt export pump (Bsep). In humans, mutations in the Spgp
      gene are associated with a fatal childhood disease, type 2 progressive familial
      intrahepatic cholestasis (PFIC2). However in mice, the "knockout" of Spgp only
      results in mild cholestasis. In this study, we fed spgp(-/-) knockout mice with a
      cholic acid (CA)-supplemented diet to determine whether a more pronounced PFIC2
      like phenotype could be induced. Such mice developed severe cholestasis
      characterized by jaundice, weight loss, elevated plasma bile acid, elevated
      transaminase, cholangiopathy (proliferation of bile ductules and cholangitis),
      liver necrosis, high mortality, and wide-ranging changes in the mRNA expression
      of major liver genes (16/36 examined). A surprising observation was that the bile
      acid output and bile flow in CA-fed mutant mice was significantly higher than
      anticipated. This suggests that the spgp(-/-) mice are able to utilize an
      alternative bile salt transport system. However, unlike Spgp, this system is
      insufficient to protect the knockout mice from cholestasis despite its high
      capacity. In conclusion, the spgp(-/-) mice provide a unique model to investigate
      molecular pathways associated with cholestasis and related diseases.

PMID- 14647061
TI  - Thyrotropin-releasing hormone in the dorsal vagal complex stimulates hepatic
      blood flow in rats.
AB  - Central administration of thyrotropin-releasing hormone (TRH) enhances hepatic
      blood flow in animal models. TRH nerve fibers and receptors are localized in the
      dorsal vagal complex (DVC), and retrograde tracing techniques have shown that
      hepatic vagal nerves arise mainly from the left DVC. However, nothing is known
      about the central sites of action for TRH to elicit the stimulation of hepatic
      blood flow. The effect of microinjection of a TRH analogue into the DVC on
      hepatic blood flow was investigated in urethane-anesthetized rats. After
      measuring basal flow, a stable TRH analogue (RX-77368) was microinjected into the
      DVC and hepatic blood flow response was observed for 120 minutes by laser Doppler
      flowmetry. Either left or right cervical vagotomy or hepatic branch vagotomy was
      performed 2 hours before the peptide. Microinjection of RX-77368 (0.5-5 ng) into
      the left DVC dose-dependently increased hepatic blood flow. The stimulation of
      hepatic blood flow by RX-77368 microinjection into the left DVC was eliminated by
      left cervical and hepatic branch vagotomy but not by right cervical vagotomy. By
      contrast, microinjection of RX-77368 into the right DVC did not significantly
      alter hepatic blood flow. These results suggest that TRH acts in the left DVC to
      stimulate hepatic blood flow through the left cervical and hepatic vagus,
      indicating that neuropeptides may act in the specific brain nuclei to regulate
      hepatic function.

PMID- 14647062
TI  - Bacterial translocation up-regulates GTP-cyclohydrolase I in mesenteric
      vasculature of cirrhotic rats.
AB  - In cirrhosis, arterial vasodilation and the associated hemodynamic disturbances
      are most prominent in the mesenteric circulation, and its severity has been
      linked to bacterial translocation (BT) and endotoxemia. Synthesis of nitric oxide
      (NO), the main vasodilator implicated, is dependent on the essential cofactor
      tetrahydrobiopterin (BH(4)). The key enzyme involved in BH(4) synthesis is GTP
      cyclohydrolase I (GTPCH-I), which is stimulated by endotoxin. Therefore, we
      investigated GTPCH-I activity and BH(4) biosynthesis in the mesenteric
      vasculature of cirrhotic rats with ascites, as well as their relationship with BT
      and endotoxemia, serum NO, and mean arterial pressure (MAP). GTPCH-I activity and
      BH(4) content in mesenteric vasculature was determined by high-performance liquid
      chromatography. BT was assessed by standard bacteriologic culture of mesenteric
      lymph nodes (MLNs). Serum endotoxin was measured by a kinetic turbidimetric
      limulus amebocyte lysate assay, and serum NO metabolite (NOx) concentrations were
      assessed by chemiluminescence. BT was associated with local lymphatic and
      systemic appearance of endotoxin and was accompanied by increases in serum NOx
      levels. GTPCH-I activity and BH(4) content in mesenteric vasculature were both
      increased in animals with BT and correlated significantly (r = 0.69, P <.01).
      Both GTPCH-I activity and BH(4) levels significantly correlated with serum
      endotoxin and NOx levels (r = 0.69 and 0.54, 0.81 and 0.53, P <.05). MAP (a
      marker of systemic vasodilatation) correlated with endotoxemia (r = 0.58, P <.03)
      and with GTPCH-I activity (r = 0.69, P <.01). In conclusion, in cirrhotic animals
      BT appears to lead to endotoxemia, stimulation of GTPCH-I, increased BH(4)
      synthesis, and further enhancement of vascular NO production that leads to
      aggravation of vasodilatation.

PMID- 14647063
TI  - DNA methylation controls the responsiveness of hepatoma cells to leukemia
      inhibitory factor.
AB  - The related members of the interleukin 6 (IL-6) family of cytokines, IL-6,
      leukemia inhibitory factor (LIF), and oncostatin M, act as major inflammatory
      mediators and induce the hepatic acute phase reaction. Normal parenchymal liver
      cells express the receptors for these cytokines, and these receptors activate, to
      a comparable level, the intracellular signaling through signal transducer and
      activator of transcription (STAT) proteins and extracellular-regulated kinase
      (ERK). In contrast, hepatoma cell lines show attenuated responsiveness to some of
      these cytokines that is correlated with lower expression of the corresponding
      ligand-binding receptor subunits. This study tests the hypothesis that the
      reduced expression of LIF receptor (LIFR) observed in hepatoma cells is mediated
      by altered DNA methylation. H-35 rat hepatoma cells that have a greatly reduced
      LIF responsiveness were treated with 5-aza-2'-deoxycytidine, an inhibitor of DNA
      methyltransferase. Surviving and proliferating cells showed reestablished
      expression of LIFR protein and function. Restriction landmark genomic scanning
      (RLGS) demonstrated genome-wide drug-induced alterations in DNA methylation
      status, with striking similarities in the demethylation pattern among
      independently derived clonal lines. Upon extended growth in the absence of 5-aza
      2'-deoxycytidine, the cells exhibit partial reversion to pretreatment patterns.
      Demethylation and remethylation of the CpG island within the LIFR promoter that
      is active in normal liver cells correlate with increased and decreased usage of
      this promoter in H-35 cells. In conclusion, these results indicate that
      transformed liver cells frequently undergo epigenetic alterations that suppress
      LIFR gene expression and modify the responsiveness to this IL-6 type cytokine.

PMID- 14647064
TI  - Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1
      suppression.
AB  - Leptin-deficient ob/ob mice show many characteristics of obesity, including
      excess peripheral adiposity as well as severe hepatic steatosis, at least in
      part, due to increased hepatic lipogenesis. Polyunsaturated fatty acids (PUFAs)
      are not only ligands for peroxisome proliferator-activated receptor (PPAR) alpha
      but are also negative regulators of hepatic lipogenesis, which is thought to be
      mediated by the repression of sterol regulatory element-binding protein (SREBP)
      1. We have previously shown that the disruption of SREBP-1 in ob/ob mice
      decreased their liver triglyceride storage. To examine whether PUFAs could reduce
      hepatic triglyceride deposition, we challenged ob/ob mice with dietary PUFA. It
      is demonstrated that PUFA markedly decreased the mature form of SREBP-1 protein
      and thereby reduced the expression of lipogenic genes such as fatty acid synthase
      (FAS) and stearoyl-CoA desaturase 1 (SCD1) in the livers of ob/ob mice.
      Consequently, the liver triglyceride content and plasma alanine aminotransferase
      (ALT) levels were decreased. Furthermore, both hyperglycemia and hyperinsulinemia
      in ob/ob mice were improved by PUFA administration, similar to the effect of
      PPARalpha activators. In conclusion, PUFAs ameliorate obesity-associated
      symptoms, such as hepatic steatosis and insulin resistance, presumably through
      both down-regulation of SREBP-1 and activation of PPARalpha.

PMID- 14647065
TI  - Inhibition of CK2 activity by TGF-beta1 promotes IkappaB-alpha protein
      stabilization and apoptosis of immortalized hepatocytes.
AB  - Nuclear factor kappaB (NF-kappaB) is an antiapoptotic factor involved in
      development, regeneration, and neoplastic progression of the liver. Previously,
      we have shown that stabilization of inhibitor kappaB (IkappaB)-alpha protein
      following treatment of hepatocytes with transforming growth factor (TGF)-beta1
      promoted NF-kappaB repression, which then permitted induction of AP-1/SMAD
      mediated liver cell death. Because basal IkappaB-alpha protein turnover is
      regulated by protein kinase CK2, here we have elucidated the regulation of CK2
      kinase activity and its role in control of NF-kappaB levels following treatment
      with TGF-beta1. We show that both messenger RNA (mRNA) and protein levels of the
      CK2alpha catalytic subunit are down-regulated following TGF-beta1 stimulation in
      murine hepatocyte cells. The ensuing inhibition of CK2 kinase activity promotes
      stabilization of IkappaB protein, which is followed by the shutoff of
      constitutive NF-kappaB activity and induction of apoptosis. Ectopic expression of
      CK2alpha inhibits TGF-beta1-induced apoptosis through sustained activation of NF
      kappaB. Conversely, expression of a kinase-dead mutant of CK2alpha potentiates
      TGF-beta1 cell killing. Importantly, we show that hepatocellular carcinomas
      (HCCs) derived from TGF-beta1 transgenic mice and human HCC cell lines display
      enhanced CK2 IkappaB kinase activity that contributes in part to an elevated NF
      kappaB activity in vivo. In conclusion, inhibition of CK2 expression levels by
      TGF-beta1 is crucial for the induction of apoptosis of hepatocytes. Circumvention
      of this process by up-regulation of CK2 activity in transformed cells may
      contribute to the promotion of TGF-beta1-induced liver carcinogenesis.

PMID- 14647066
TI  - Growth hormone stimulates proliferation of old-aged regenerating liver through
      forkhead box m1b.
AB  - The Forkhead Box (Fox) proteins are an extensive family of transcription factors
      that shares homology in the winged helix DNA-binding domain and the members of
      which play essential roles in cellular proliferation, differentiation, and
      longevity. Reduced cellular proliferation during aging is associated with a
      progressive decline in both growth hormone (GH) secretion and Foxm1b expression.
      Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated
      that increased hepatocyte expression of Foxm1b alone is sufficient to restore
      hepatocyte proliferation to levels found in 2-month-old (young) regenerating
      liver. GH therapy in older people has been shown to cause an increase in cellular
      proliferation, but the transcription factors that mediated this stimulation in
      proliferation remain uncharacterized. In this study, we showed that human GH
      administration to old-aged Balb/c mice dramatically increased both expression of
      Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged
      regenerating hepatocyte proliferation was associated with elevated protein
      expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of
      cyclin-dependent kinase inhibitor p27(Kip1) (p27). GH treatment also was found to
      stimulate hepatocyte proliferation and expression of Foxm1b protein without
      partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b -/- mice
      failed to restore regenerating hepatocyte DNA replication and mitosis caused by
      Foxm1b deficiency. These genetic studies provided strong evidence that the
      presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte
      proliferation. In conclusion, our old-aged liver regeneration studies show that
      increased Foxm1b levels are essential for GH to stimulate hepatocyte
      proliferation, thus providing a mechanism for GH action in the elderly.

PMID- 14647067
TI  - Dexamethasone inhibits early regenerative response of rat liver after cold
      preservation and transplantation.
AB  - Regeneration is crucial for the recovery of hepatic mass following liver
      transplantation. Glucocorticoids, immunosuppressive and antiinflammatory agents
      commonly used in transplantation, are known to inhibit the expression of specific
      cytokines and growth factors. Some of these proteins, namely tumor necrosis
      factor alpha (TNF-alpha) and interleukin 6 (IL-6), play a critical role in the
      initiation of liver regeneration. Following cold preservation and reperfusion of
      the transplanted liver, the normal recovery process is marked by increased
      expression of TNF-alpha and IL-6, followed by activation of cytokine-responsive
      transcription factors and progression of the cell cycle resulting in hepatocyte
      proliferation. We hypothesized that glucocorticoids may influence the repair
      mechanisms initiated after extended cold preservation and transplantation. Using
      a rat orthotopic liver transplant model, recipient animals were treated with
      dexamethasone at the time of transplantation of liver grafts with prolonged cold
      storage (16 hours). Treatment with dexamethasone suppressed and delayed the
      expression of TNF-alpha and IL-6 compared with animals receiving no treatment and
      attenuated downstream nuclear factor kappaB (NF-kappaB), signal transduction and
      activator of transcription 3 (STAT3), and activation protein 1 (AP-1) activation.
      This suppression was accompanied by poor cell-cycle progression, delayed cyclin
      D1 nuclear transposition, and impaired hepatocyte proliferation by BrdU uptake.
      Histologically, the liver grafts in treated animals demonstrated more injury than
      controls, which appeared to be necrosis, rather than apoptosis. In conclusion,
      these data provide evidence that the administration of glucocorticoids at the
      time of transplantation inhibits the initiation of the regenerative process and
      may have a deleterious effect on the recovery of liver grafts requiring
      significant regeneration. This may be particularly relevant for transplantation
      of partial liver grafts in the living donor setting.

PMID- 14647068
TI  - A key pathogenic role for the STAT1/T-bet signaling pathway in T-cell-mediated
      liver inflammation.
AB  - TH1 cytokines have been suggested to contribute to the pathogenesis of T-cell
      mediated liver injury and inflammation. However, the molecular signaling pathways
      involved in such injury are still poorly understood. In the present study, we
      investigated the role of the STAT1/T-bet signaling pathway in a murine model of T
      cell-mediated liver inflammation induced by the application of concanavalin A
      (Con A) using newly created STAT1 transgenic mice as well as STAT1- and T-bet
      deficient mice. Liver injury induced by Con A was associated with an increase of
      both pSTAT1 and T-bet levels in the liver. Furthermore, functional studies
      suggested a pathogenic role for STAT1 in Con A-induced liver injury, because
      transgenic mice overexpressing STAT1 under the control of the CD2
      promoter/enhancer construct showed elevated interferon gamma (IFN-gamma) and IRF
      1 levels as well as significantly augmented liver injury following administration
      of Con A. Consistently, we observed that both STAT1-deficient and T-bet-deficient
      mice were protected from such T-cell-dependent liver injury. In conclusion, these
      findings suggest a key pathogenic role for the STAT1/T-bet signaling pathway for
      T-cell activation in the Con A model of T-cell-mediated liver pathology.

PMID- 14647069
TI  - Viral kinetics and hepatitis C.

PMID- 14647070
TI  - Resolving the role of IL-6 in liver regeneration.

PMID- 14647071
TI  - Apolipoprotein E4 allele is associated with poor treatment response in hepatitis
      C virus (HCV) genotype 1.

PMID- 14647072
TI  - Tyranny of algorithms in the treatment of patients with hepatitis C.

PMID- 14647073
TI  - A sheep in wolf's clothing.

PMID- 14647076
TI  - Research: ADA's commitment.

PMID- 14647077
TI  - Ensuring a healthy start is part of Head Start.

PMID- 14647078
TI  - Childhood eating patterns: the roles parents play.

PMID- 14647079
TI  - Research your profession: the 2002 Dietetics compensation & benefits survey.

PMID- 14647081
TI  - Reading "worth" more than presenting research?

PMID- 14647083
TI  - Preliminary report of the State Issues Task Force: trends affecting the dietetics
      profession.

PMID- 14647084
TI  - Milk--good for bones, good for reducing childhood obesity?

PMID- 14647085
TI  - An ad libitum, very low-fat diet results in weight loss and changes in nutrient
      intakes in postmenopausal women.
AB  - OBJECTIVES: To determine whether a very low-fat diet (<15% of energy intake)
      consumed ad libitum during an 8-month period can achieve weight loss of 5% to 10%
      of initial body weight while still providing adequate intakes of other essential
      nutrients. DESIGN: Longitudinal, 8-month, ad libitum, free living, very low-fat
      diet trial. SUBJECTS: Fifty-four of the sixty-four healthy postmenopausal women
      recruited completed the entire study (age 59+/-8 years, BMI=29.6+/-6.3). Twenty
      four of these women used hormone replacement therapy, thirty women did not.
      INTERVENTION: Weekly sessions aimed at teaching and reinforcing a very low-fat
      intake diet for eight months. MAIN: outcome measures Body weight, percent body
      fat, waist-to-hip ratio, resting energy expenditure, respiratory quotient, and
      nutrient intakes derived from 7-day food records at the beginning and at 2, 4, 6,
      and 8 months of the study. Statistical analysis performed Repeated measures
      analysis of variance and Tukey post hoc analysis were used to analyze significant
      differences in mean data (P<.05). RESULTS: Fat intake decreased from 33.2+/-7.5%
      to 11+/-4% over the 8-month intervention period (P<.00001). Weight loss was 6.0
      kg+/- 4.2 kg (P<.000038), an 8% weight change, and decrease in percent body fat
      of 2.7%+/-0.2% (P< or =.000046). Weight correlated better with the self-reported
      fat intake (r=0.321, P<.01) than the energy intake (r=0.263, P<.05) at baseline.
      Fiber intake increased from 16 g+/-0.6 g to 23 g+/-0.2 g (P<.0005). All
      micronutrient intakes remained at or above preintervention ranges, except for a
      decrease in vitamin E intake from 8.1 mg+/-4.0 mg to 3.7 mg+/-1.1 mg (P<.0005) on
      the very low-fat diet and linoleic acid from 6.3%+/-1.5% to 2.5%+/-0.7%
      (P<.000001) with no significant reduction in linolenic acid. Hormone replacement
      was not associated with the amount of weight loss. APPLICATIONS: This study
      demonstrates that adherence to a very low-fat diet consumed ad libitum causes
      weight loss in the 5% to 10% range and a reduction of body fat. These reductions,
      along with the observed decreases in fat intake, are associated with improved
      health outcomes. Because of the decreased vitamin E and n-3 fatty acid intake,
      emphasis on foods high in these nutrients may need to be encouraged for those
      consuming a very low-fat diet.

PMID- 14647086
TI  - Lack of effect of sucralose on glucose homeostasis in subjects with type 2
      diabetes.
AB  - OBJECTIVE: To investigate the effect of 3-months' daily administration of high
      doses of sucralose, a non-nutritive sweetener, on glycemic control in subjects
      with type 2 diabetes. DESIGN: A multicenter, double-blind, placebo-controlled,
      randomized study, consisting of a 6-week screening phase, a 13-week test phase,
      and a 4-week follow-up phase. SUBJECTS/SETTING: Subjects with type 2 diabetes
      (age range 31 to 70 years) entered the test phase of this study; 128 subjects
      completed the study. The subjects were recruited from 5 medical centers across
      the United States and were, on average, obese. INTERVENTION: Subjects were
      randomly assigned to receive either placebo (cellulose) capsules (n=69) or 667 mg
      encapsulated sucralose (n=67) daily for the 13-week test phase. All subjects
      blindly received placebo capsules during the last 4 weeks of the screening phase
      and for the entire 4-week follow-up phase. MAIN OUTCOME MEASURES: Glycated
      hemoglobin (HbA1c), fasting plasma glucose, and fasting serum C-peptide were
      measured approximately every 2 weeks to evaluate blood glucose homeostasis. Data
      were analyzed by analysis of variance using repeated measures. RESULTS: There
      were no significant differences between the sucralose and placebo groups in
      HbA1c, fasting plasma glucose, or fasting serum C-peptide changes from baseline.
      There were no clinically meaningful differences between the groups in any safety
      measure. CONCLUSIONS: This study demonstrated that, similar to cellulose,
      sucralose consumption for 3 months at doses of 7.5 mg/kg/day, which is
      approximately three times the estimated maximum intake, had no effect on glucose
      homeostasis in individuals with type 2 diabetes. Additionally, this study showed
      that sucralose was as well-tolerated by the study subjects as was the placebo.

PMID- 14647087
TI  - Ready-to-eat cereal consumption: its relationship with BMI and nutrient intake of
      children aged 4 to 12 years.
AB  - OBJECTIVE: To examine the relationship between ready-to-eat cereal consumption
      habits and body mass index of a sample of children aged 4 to 12 years. DESIGN:
      Fourteen-day self-reported food diary records were obtained from a sample of
      2,000 American households from February 1998 through February 1999. Height and
      weight of the family members were also self-reported. SUBJECTS/SETTING: The
      sample population of 603 children, aged 4 to 12 years, was broken into tertiles
      based on cereal consumption over the 14 days: (three or fewer, four to seven, or
      eight or more servings). STATISTICAL ANALYSIS: Logistic regression and analysis
      of variance were used to determine associations between frequency of ready-to-eat
      cereal consumption and body mass index or nutrient intakes. RESULTS: More than
      90% of children aged 4 to 12 years consumed ready-to-eat cereal at least once in
      the two-week collection period. Within tertiles of consumption, children in the
      upper tertile had lower mean body mass indexes than those in the lowest tertile
      consistently across all age groups (P<.01). Additionally, the proportion of
      children aged 4 to 12 years who were at risk for overweight/overweight was
      significantly lower in the upper tertile of cereal consumption (P<.05). Children
      in the upper tertile also had lower fat intakes and higher intakes of many
      micronutrients. APPLICATIONS: The consumption of ready-to-eat cereals at
      breakfast should be encouraged as a component of an eating pattern that promotes
      the maintenance of healthful body weights and nutrient intakes in children.

PMID- 14647088
TI  - A comparison of nutrient intake between infants and toddlers with and without
      cystic fibrosis.
AB  - OBJECTIVE: To compare the micronutrient and energy intake of infants and toddlers
      with cystic fibrosis (CF) to the intake of matched control children and dietary
      reference index (DRI) levels. DESIGN: A two-group comparison study. Nutrient and
      energy intakes were measured via 3-day diet diaries. Anthropometric data were
      collected within 1 week of study enrollment. SUBJECTS/SETTING: A clinical sample
      of 35 infants and toddlers with CF (mean=18.6, SD=8.1 months) matched to a
      community sample of 34 healthy controls. STATISTICAL ANALYSES PERFORMED: Children
      with CF and controls were compared on anthropometric and nutrient data using
      independent sample t tests. Mean nutrient and energy intake for children in each
      group were compared with the age-appropriate DRI for targeted nutrients using
      percentages. RESULTS: Children with CF and controls were similar on measures of
      growth (height, weight, or weight-for-height percentile). Four children with CF
      were at or below the 10th percentile for weight-for-height, compared with one
      control child. Children with CF and controls did not differ on average daily
      protein, calcium, zinc, and energy intake. Overall, children met or exceeded DRI
      levels for nutrient intakes. A notable exception was iron, for which mean intakes
      were lower for control children. Toddlers with CF consumed only 89% of the RDA
      per day for energy. APPLICATIONS/CONCLUSIONS: Infants and toddlers with CF are
      likely obtaining adequate micronutrient intakes from food. Interventions to
      increase total energy intake in infants and toddlers with CF are needed.
      Dietitians may want to focus more on calorie intake and percent calories from fat
      than on micronutrient intake in their nutrition counseling in young children with
      CF.

PMID- 14647089
TI  - Longitudinal calcium intake is negatively related to children's body fat indexes.
AB  - OBJECTIVE: To determine if dietary calcium was negatively related to children's
      body fat (BF), if BF indexes and calcium intakes changed over time, and to
      identify variables related to BF and calcium intake. DESIGN: Percent BF and kg BF
      were assessed by dual energy x-ray absorptiometry (DEXA) in 8-year-old children.
      In a prospective design, height, weight, dietary intakes, and related variables
      were monitored longitudinally from ages 2 months to 8 years during in-home
      interviews. SUBJECTS: Fifty-two white children, (n=25 boys, 27 girls)
      participated in a longitudinal study with their mothers. At 8 years of age, mean
      BMI was 17.3+/-2.1 (standard deviation) for boys and 17.1+/-2.5 for girls.
      ANALYSES: Regression analysis of all variables, followed by further regression
      analysis on selected models. RESULTS: At 8 years, percent BF was 22.7+/-6.7 for
      boys and 26.2+/-7.9 for girls, as assessed by DEXA. Dietary calcium (mg) and
      polyunsaturated fat intake (g) were negatively related to percent BF (P=.02
      to.04) in 3 statistical models, which predicted 28% to 34% of the variability in
      BF among children. Variables positively associated with percent BF were total
      dietary fat (g) or saturated fat (g), female gender, sedentary activity
      (hours/day), father's BMI, and mothers' percent BF. Calcium intakes were
      significantly correlated over time. Dietary variety was positively related to
      calcium intake, and intakes of carbonated beverages and other sweetened beverages
      were negatively related. APPLICATIONS/CONCLUSIONS: Children should be strongly
      encouraged to regularly include calcium-rich foods and beverages in their diets.

PMID- 14647090
TI  - Registered dietitians' use of physical assessment parameters in professional
      practice.
AB  - OBJECTIVE: To examine how registered dietitians who have completed one of two
      physical assessment programs use the knowledge and skills learned in practice and
      whether method of instruction had an affect on use of skills in practice.
      SUBJECTS/SETTING: Surveys were mailed to 891 persons, all of whom completed a
      Dietitians in Nutrition Support dietetic practice group or University of Medicine
      and Dentistry of New Jersey continuing education program. Four hundred seventeen
      surveys were returned and 407 were usable. STATISTICAL ANALYSIS: chi(2) analysis
      and stepwise logistic regression was used to analyze the data. Statistical
      significance was P=.05. RESULTS: Sixty percent of respondents worked in a clinic
      setting. Four of the five most-used competencies were similar between the two
      programs. More registered dietitians are using physical assessment competency
      information in clinical assessment, but not performing the competencies
      independently. Respondents with the Certified Diabetic Educator credential
      (P=.007) and Certified Nutrition Support Dietitians credential (P=.215) were more
      likely to use select physical assessment competencies. Confidence was reported as
      enhancing use of physical assessment competencies (n=153, 45%) and time was a
      barrier to using physical assessment competencies (n=159, 52%).
      APPLICATIONS/CONCLUSIONS: There were no significant differences in use of
      physical assessment competencies between the University of Medicine and Dentistry
      of New Jersey program and the Dietitians in Nutrition Support program. Although
      not statistically significant, there appeared to be more use of physical
      assessment competencies by those who received additional training and those who
      completed the University of Medicine and Dentistry of New Jersey program. This
      study reveals that registered dietitians are using the values in clinical
      assessment, however they must move to actually performing physical assessment
      competencies in practice.

PMID- 14647091
TI  - Practice point: Choosing between inexpensive and impersonal RD learning methods.

PMID- 14647092
TI  - Applying the theory of planned behavior to promotion of whole-grain foods by
      dietitians.
AB  - The objective of this preliminary study was to apply the theory of planned
      behavior to explain dietitians' intentions to promote whole-grain foods. Surveys
      were mailed to a random national sample of registered dietitians to assess
      knowledge and attitudinal, normative, and control beliefs regarding intention to
      promote whole-grain foods, with a 39% return rate (n=776, with 628 usable surveys
      from those working in direct patient care). About half of the respondents had a
      master's degree, and 58% had substantial experience in the dietetics field. The
      theory of planned behavior explained intention to promote whole grains to a
      moderate extent (df=3, F=74.5, R(2)=0.278, P<.001). Most were positive about the
      health benefits, and few perceived barriers to promotion. However, many had low
      levels of knowledge and self-efficacy regarding ability to help clients consume
      more whole-grain foods. Continuing education for dietitians should use strategies
      that enhance self-efficacy regarding ability to promote whole-grain foods.

PMID- 14647093
TI  - Identification of factors affecting purchasing and preparation of fruit and
      vegetables by stage of change for low-income African American mothers using the
      think-aloud method.
AB  - The objective of this study was to identify factors affecting the purchase and
      preparation of fruits and vegetables according to stage of change for low-income
      African American women with young children. The think-aloud method was used to
      collect verbalization data in grocery stores as women shopped (N=70) and in their
      homes during meal preparation (N=68). Audiotaped verbalizations were transcribed
      verbatim before encoding. Content analysis procedures were used to identify
      common themes by stage of change. Factors affecting decision making that varied
      by stage of change were preferences and specific needs (eg, for meals, for family
      members). Preferences regarding variety, quantity, color, and liking were more
      often expressed by women in later stages. Women in the later stages also often
      used meal-planning skills to include fruits and vegetables in meals.
      Interventions could be tailored according to selected factors regarding purchase
      and preparation of fruits and vegetables by stage of change to contribute to
      greater changes in intake.

PMID- 14647094
TI  - Food handling behaviors of special importance for pregnant women, infants and
      young children, the elderly, and immune-compromised people.
AB  - This study used a Web-based Delphi process with a group of nationally recognized
      food safety experts to identify food-handling behaviors of special importance in
      reducing the risk of foodborne illness among pregnant women, infants and young
      children, elderly people, and people with compromised immune systems because of
      disease or pharmacologic therapy. Behaviors were related to 13 pathogens. Top
      rated behaviors for pregnant women were associated with Listeria monocytogenes,
      Toxoplasma gondii, and Salmonella species. Top-rated behaviors for infants and
      young children, elderly people, and immune-compromised people were associated
      with a number of different pathogens. The results should help dietetics
      professionals and community health educators focus their efforts on those
      behaviors of special importance to the population being targeted.

PMID- 14647095
TI  - Vitamin K content of nuts and fruits in the US diet.
AB  - Assessment of vitamin K dietary intakes has been limited by incomplete vitamin K
      food composition data for the US food supply. The phylloquinone (vitamin K(1))
      concentrations of nuts (n=76) and fruits (n=215) were determined by high
      performance liquid chromatography. Each sample represented a composite of units
      obtained from 12 to 24 outlets, which provided geographic representation of the
      US food supply. With the exception of pine nuts and cashews, which contain 53.9
      and 34.8 microg of phylloquinone per 100 g of nut, respectively, nuts are not
      important dietary sources of vitamin K. Similarly, most fruits are not important
      sources of vitamin K, with the exception of some berries, green fruits, and
      prunes. Menu planning for patients on warfarin can include a healthy diet
      including fruits and nuts without compromising the stability of their oral
      anticoagulation therapy.

PMID- 14647096
TI  - Excessive maternal weight gain patterns in adolescents.
AB  - The objective of this study was to examine the correlates of excessive maternal
      weight gain among adolescent mothers in the United States. Data from the Centers
      for Disease Control & Prevention 2000 natality file were analyzed to examine
      weight gain among adolescents (< or=19 years) compared with their older
      counterparts (> or=20 years). Using the Institute of Medicine guidelines, we
      defined excessive weight gain as more than 40 pounds. Our study population was
      restricted to singleton births, delivered after 36 weeks of gestation, who did
      not live in California. Maternal weight gain distributions were tabulated by
      maternal age and other maternal characteristics. Demographic characteristics
      potentially associated with maternal weight gain were compared for adolescents
      and older mothers. We further evaluated the role of parity and maternal race on
      the relationship between excessive weight gain and maternal age. Odds ratios and
      95% confidence intervals were estimated using logistic regression. Over 27% of
      adolescent mothers gained excessive weight during pregnancy, although
      approximately 18% of their older counterparts gained more than 40 pounds. The
      association between young maternal age and weight gain was stronger for
      primiparous women than multiparous women and stronger among non-Hispanic white
      and non-Hispanic black mothers than Hispanic mothers. Adolescents were more
      likely to gain excessive weight than their older counterparts in nearly all
      demographic categories, regardless of parity or race. Adolescents are at high
      risk of gaining an excessive amount of weight during pregnancy and should be
      monitored during pregnancy by dietetics professionals.

PMID- 14647105
TI  - Infection control practices among tattooists and body piercers in Sydney,
      Australia.
AB  - BACKGROUND: Tattooing and body piercing have a long history, and both have become
      increasingly fashionable worldwide. There is an association between
      tattooing/body piercing and hepatitis B and C infections. METHOD: We undertook an
      observational study to examine the prevalence and predictors of infection control
      practices among tattooists and body piercers in Sydney, Australia. Within each
      premise, data were obtained from owners/mangers and nominated staff completion of
      a knowledge and attitudes questionnaire, owner/manager demonstration of key
      infection control procedures, and an inspection of the premises. RESULTS: Consent
      to participate was obtained in 41 of 44 premises (93.2%). A low proportion of
      owners/managers and staff gave the correct answer for the purpose of disinfection
      (52.8%/26.9%) and sterilization (50%/53.8%). About one third of owners/managers
      (38.8%) and 56% of staff reported that their infection control compliance could
      be improved. Approximately one quarter of owners/managers reported that the
      frequency of inspections was inadequate. Even though the majority of
      demonstration and inspection items were complied with, deficiencies were observed
      concerning washing of hands, wearing of gloves, and sterilization procedures.
      CONCLUSION: There is a continuing need to improve infection control performance
      among tattooists and body piercers. The effectiveness of intervention approaches
      designed to achieve this should be explored.

PMID- 14647106
TI  - The measurement of influenza vaccine coverage among health care workers.
AB  - BACKGROUND: Annual influenza vaccination is recommended for health care workers
      in both the United States and Canada. Estimations of vaccine coverage are
      commonly used to evaluate these vaccination programs. PURPOSE: We identify,
      discuss, and illustrate challenges including definitions of health care worker
      (HCW), selection of indicators, and data sources in the estimation of staff
      influenza vaccination coverage rates. METHODS: To illustrate the impact of the
      factors we discuss, we created a database of a simulated pool of HCWs that
      included varying proportions of permanent, casual, and contract staff under
      differing scenarios of staff turnover and differing probabilities of individuals
      being vaccinated. The Excel 97 random number generator (Microsoft) was used to
      randomly allocate the HCW to different strata under differing staff turnover
      rates and to designate individuals as being vaccinated. RESULTS: The nature of
      the staff targeted in the program policy has a large impact on the estimations of
      vaccine coverage. Different indicators provide data that might be useful for
      different purposes. The counts in the numerator and denominator of a period
      prevalence may be useful for estimation of the total workload required of the
      vaccination program. An incidence density might be useful as an indicator of the
      efficiency of the program in "capturing" staff for vaccination. The indicator
      that may be easiest is the point prevalence. CONCLUSION: Program evaluators must
      think carefully when planning to estimate staff vaccination coverage to avoid
      invalid comparisons of estimates over time and place. State or province-wide
      targets for health care worker (HCW) vaccination may be meaningless unless
      appropriate criteria for the calculation of influenza vaccination rates are
      developed and specified.

PMID- 14647107
TI  - Resistance to the migration of microorganisms of a needle-free disinfectable
      connector.
AB  - The aim of this study was to assess the efficacy of a disinfectable needle-free
      connector in reducing the pass of micro-organisms to the lumen of the catheter. A
      prospective, controlled, experimental trial was performed in which a laboratory
      model simulated the insertion of a peripheral venous catheter. Catheters inserted
      in sterile conditions in a hemoculture bottle were closed with the disinfectable
      needle-free connector (study group) or with a cap (control group). After 9 days
      of contamination and manipulation of the connector and cap external surfaces,
      100% of bottles in the control group were contaminated whereas 60% remained
      sterile in the study group. The disinfectable needle-free connector showed more
      resistance to the pass of microorganisms than the conventional cap according to
      our experimental model.

PMID- 14647108
TI  - National nosocomial infection surveillance system-based study in Iran: additional
      hospital stay attributable to nosocomial infections.
AB  - BACKGROUND: Nosocomial infection is a serious health and financial problem. The
      purpose of this study was to determine the extra hospital stay attributable to
      nosocomial infections for patients undergoing surgery. METHOD: All patients
      undergoing surgery admitted from March 1, 1999, to February 28, 2000, to the 38
      bed general surgery ward within a university hospital in Shiraz, Iran, were
      included in this study. The study was planned as a pairwise-matched case-control
      study nested in cohort design. A case was defined as any patient with 1 of 4 of
      the following nosocomial infections: urinary tract infection; surgical site
      infection; bloodstream infection; or pneumonia, whereby definitions for the
      nosocomial infections were on the basis of National Nosocomial Infection
      Surveillance system definitions. For each patient, an appropriate match was
      selected, which resulted in 69 pairs of study patients. RESULTS: The total
      incidence of nosocomial infection during the study period was 17.59%. The mean
      extra length of hospitalization as a result of all major kinds of nosocomial
      infections was 6.62 days total, which was obtained using 4.4, 5.33, 8.73, and 9.2
      extra days for urinary tract infection, pneumonia, surgical site infection, and
      bloodstream infection, respectively. CONCLUSION: Nosocomial infections add
      considerable costs to the health care system in Iran. Therefore, the development
      of strategies and concepts to reduce the incidence of nosocomial infections is
      cost-effective and warranted, and an appropriate surveillance system on the basis
      of international criteria is the cornerstone for this task.

PMID- 14647109
TI  - Occupational exposure to needlestick injuries and hepatitis B vaccination
      coverage among health care workers in Egypt.
AB  - BACKGROUND: The health care worker (HCW) is at substantial risk of acquiring
      bloodborne pathogen infections through exposure to blood or infectious body
      fluids. Hepatitis B vaccination of HCWs and optimal HCW practices regarding
      management of sharps can minimize these risks. This study explores the frequency
      of exposure to needlestick injuries and the hepatitis B vaccination coverage
      among HCWs in Egypt. METHODS: All HCWs available in a 25% random sample of
      different types of health care facilities from 2 governorates in Egypt (Nile
      Delta and Upper Egypt) were included in the study. A total of 1485 HCWs were
      interviewed. History of exposure to needlestick injuries, vaccination status, and
      socioeconomic data were collected. RESULTS: Of the 1485 HCWs interviewed, 529
      (35.6%) were exposed to at least 1 needlestick injury during the past 3 months
      with an estimated annual number of 4.9 needlesticks per worker. The most common
      behavior associated with needlestick injuries was 2-handed recapping. Overall,
      64% of HCWs disposed of needles unsafely in nonpuncture-proof containers. Overall
      15.8% of HCWs reported receiving 3 doses of hepatitis B vaccine. Vaccination
      coverage was highest among professional staff (38%) and lowest among housekeeping
      staff (3.5%). Using Kane's model to predict infections after needlestick
      exposures, we estimate 24,004 hepatitis C virus and 8617 hepatitis B virus
      infections occur each year in Egypt as a result of occupational exposure in the
      health care environment. CONCLUSION: High rates of needlestick injuries and low
      vaccination coverage contribute highly to the rates of viral hepatitis infections
      among HCWs. Prevention of occupational infection with bloodborne pathogens should
      be a priority to the national program for promotion of infection control.
      Training of HCWs on safe handling and collection of needles and sharps, and
      hepatitis B vaccination of all HCWs is required to reduce transmission.

PMID- 14647110
TI  - The attributable cost, length of hospital stay, and mortality of central line
      associated bloodstream infection in intensive care departments in Argentina: A
      prospective, matched analysis.
AB  - BACKGROUND: Limited information is available on the financial impact of central
      venous catheter-associated bloodstream infection (BSI) in Argentina. To calculate
      the cost of BSIs in the intensive care department (ICU), a 5-year prospective
      nested case-control study was undertaken at 3 hospitals in Argentina. METHODS: We
      studied 6 adult ICUs from 3 hospitals. In all, 142 patients with BSI and 142
      control patients without BSI were matched for hospital, type of ICU, year of
      admission, length of stay, sex, age, and average severity of illness score.
      Patients' length of stay in the ICU was obtained prospectively on daily rounds.
      The hospitals' finance departments provided the cost of each ICU day. The
      hospitals' pharmacies provided the cost of antibiotics prescribed for BSIs.
      RESULTS: The mean extra length of stay for patients with BSI compared with
      control patients was 11.9 days, the mean extra antibiotic defined daily dose was
      22.6, the mean extra antibiotic cost was $1913, the mean extra cost was $4888.42,
      and the excess mortality was 24.6%. CONCLUSIONS: In this study, patients with
      central venous catheter-associated BSI experienced significant prolongation of
      hospitalization, increased use of health care costs, and a higher attributable
      mortality. These findings support the need to implement preventative
      interventions for patients hospitalized with central venous catheters in
      Argentina.

PMID- 14647111
TI  - National Nosocomial Infections Surveillance (NNIS) System Report, data summary
      from January 1992 through June 2003, issued August 2003.

PMID- 14647112
TI  - The Food and Drug Administration should regulate medical devices--not hospitals.

PMID- 14647113
TI  - Transmission of hepatitis C by blood splash into conjunctiva in a nurse.
AB  - The risk of transmission of hepatitis C virus (HCV) infection is an important
      problem for the health care worker. HCV transmission by blood splashing into eyes
      is very rare. In a hemodialyses department, a 23-year-old female nurse splashed
      blood from a patient who was anti-HCV positive into her eyes. She washed her eyes
      with water immediately and reported to the infection control department. She had
      never used intravenous drugs nor received transfusions. At the time of exposure,
      there was no abnormality in her laboratory tests. Her anti-HCV and HCV-RNA tests
      produced negative results. She was followed up for anti-HCV and alanine
      aminotransferase activity. After 6 months, she presented with sore throat,
      nausea, vomiting, fatigue, and weight loss. She had icterus and hepatomegalia. In
      laboratory tests, alanine aminotransferase level was 504 U/L, aspartate
      aminotransferase level was 388 U/L, and anti-HCV and HCV-RNA tests produced
      positive findings. She was treated with interferon alfa-2a for a 1-year period.
      After treatment, an HCV-RNA test produced negative results and transaminase
      levels were normal. In conclusion, splashing blood from patients who are HCV
      positive into the face or eyes is a risk for health care workers. They should be
      educated to prevent a nosocomial acquisition of bloodborne infection and they
      should observe protective precautions.

PMID- 14647114
TI  - A prospective incidence study of nosocomial infections in a neonatal care unit.
AB  - BACKGROUND: Health care improvements and technical advances for diagnostic and
      therapeutic management in the neonatal care unit (NCU) have made possible the
      increasing survival of neonates with severe pathologic conditions. However,
      nosocomial infections (NI) still represent an important cause of morbidity and
      mortality in this population. OBJECTIVE: To describe the epidemiologic profile of
      NI in the NCU. METHODS: A prospective surveillance study was performed in the NCU
      at a university hospital in Barcelona during 6 months. Two hundred sixty-eight
      neonates were admitted during the study period. Centers for Disease Control and
      Prevention criteria were used as standard definitions for NI. Data including risk
      factors associated with NI were recorded. RESULTS: Sixty-five neonates had a
      total of 88 NI. The incidence rate of NI was 1.6 per 100 patient-days. The
      accumulative rate of NI was 32.7 per 100 admissions. Bacteremia (28.4%),
      conjunctivitis (19.5%), respiratory infection (10.2%), and urinary tract
      infection (7.9%) were the most common episodes observed. Gram-positive bacteria
      were the most commonly isolated germs (76.4%), with coagulase-negative
      Staphylococcus (72.5%) being the main pathogen. Intrinsic risk factors related to
      NI were low birth weight (<1000 g) and urinary catheter and peripheral venous
      catheter (P<.01). CONCLUSIONS: NI represent an important and frequent problem in
      neonates. Knowledge of the incidence of NI allows the targeting and
      implementation of preventive strategies for reducing morbidity and mortality
      related to NI in an NCU.

PMID- 14647115
TI  - Clinical comparisons of La Crosse encephalitis and enteroviral central nervous
      system infections in a pediatric population: 2001 surveillance in East Tennessee.
AB  - BACKGROUND: La Crosse encephalitis (LAC) is a mosquito-borne illness that
      primarily affects children. In 1997, an initial cluster of cases was identified
      by the regional pediatric referral center in East Tennessee. Since that time,
      public health officials, pediatric infectious disease physicians, infection
      control nurses, laboratory personnel, entomologists, and Centers for Disease
      Control and Prevention consultants have collaborated to provide ongoing
      surveillance activities. Studies comparing LAC cases with non-LAC (no etiologic
      diagnosis) central nervous system infections have yielded no statistical
      significance in signs and symptoms or laboratory values. OBJECTIVE: To determine
      any differences in signs, symptoms, and/or diagnostic laboratory values between
      LAC cases and enteroviral central nervous system (EV-CNS) infections. METHODS: In
      2001, descriptive public health surveillance for LAC was performed concurrent
      with an outbreak investigation of EV-CNS infections at a pediatric referral
      center in East Tennessee. All patients being evaluated for suspected meningitis
      and/or encephalitis were interviewed for signs and symptoms of illness. Patients
      with positive test results for LAC and negative results for EV or positive
      results for EV and negative results for LAC were included in the study. RESULTS:
      Compared with patients with EV-CNS infection, patients with LAC were
      significantly more likely to have aphasia (P=.001), loss of consciousness
      (P=.0003), seizure (P=.0003), and admission to the pediatric intensive care unit
      (P=.02). Presence of fever, headache, vomiting, stiff neck (subjective),
      photophobia, behavioral changes, confusion, need for mechanical ventilation, age,
      and sex showed no statistical significance (P>.05). Statistical differences were
      not demonstrated in cerebrospinal fluid laboratory values (P>.05). CONCLUSION:
      Patients with LAC demonstrated more severe symptoms on presentation to the
      hospital than did patients with EV-CNS infection. A possible advantage of
      identifying specific viral etiologic factors of pediatric CNS disease by clinical
      characteristics may be the ability to take advantage of emerging antiviral
      therapies.

PMID- 14647116
TI  - An innovative approach to training hospital-based clinicians for bioterrorist
      attacks.
AB  - The recent attacks of September 11, 2001, and the subsequent dissemination event
      of anthrax in the United States demonstrated the necessity for hospitals to
      initiate bioterrorism education for clinicians. Events such as the release of
      sarin gas into the Tokyo subway by the Aum Shinrikyo cult provided some insight
      into how quickly emergency medical personnel may be overwhelmed by causalities of
      unconventional weapons. Educational interventions to prepare hospital-based
      practitioners for such disasters must fit among the demands of patient care,
      administrative duties, and continuing education within specialties. In addition,
      the priority placed on the topic, confusion about reputable resources to consult,
      and concerns of funding for preparedness training mandate the need for an
      authoritative, comprehensive, and easily accessible approach. A pilot project
      supported in part by the Agency for Healthcare Research and Quality was developed
      to facilitate streamlining of preparedness efforts through the implementation of
      interactive screen savers as an alternative to traditional educational
      modalities. This report presents the successful application of this model, which
      was quantified with pretests and posttests given to users of the system.

PMID- 14647117
TI  - The presence of nucleic acids does not demonstrate the presence of living
      microbes.

PMID- 14647118
TI  - Awareness of tuberculosis among primary care physicians in low-incidence areas.

PMID- 14647119
TI  - Evaluation of aloe vera gel gloves in the treatment of dry skin associated with
      occupational exposure.

PMID- 14647120
TI  - Reader reaction and AJIC editorial board response: strategic directions for the
      journal.

PMID- 14647121
TI  - Neuroarthropathy of the extremities: magnetic resonance imaging features.
AB  - The objective of this article was to review the magnetic resonance imaging (MRI)
      findings of four different neuroarthropathic extremities, and discuss the role of
      MRI in establishing a correct diagnosis. The shoulder, ankle, and knee had
      predominantly atrophic neuroarthropathic changes, whereas both atrophic and
      productive changes could be seen in the elbow. Bone marrow edema, suggesting a
      recent stress fracture, was detected in the elbow and knee. Osteochondral
      defects, or "detritic" synovitis with effusion, were extensive in all joints but
      exceptionally profound in the shoulder with amputation-like osteolysis and a
      total loss of the humeral head. Radiologists may encounter the joint
      manifestations of neuropathy, which may be confused with various pathologies,
      including tumor and septic arthritis, before the neurological diagnosis is
      established. MRI is helpful in detecting the extension of the disease as well as
      to differentiate chronic Charcot's arthropathy from septic arthritis before
      radiographic findings suggest the diagnosis.

PMID- 14647122
TI  - Biliary cystic disease.
AB  - Cystic diseases of the biliary tract encompass a complex group of congenital
      disorders. Some of the disorders, such as Caroli disease and the hepatobiliary
      cysts of autosomal-dominant polycystic kidney disease, share common embryologic
      origins, whereas others, such as choledochal cysts, biliary diverticula, and
      choledochoceles, have unclear origins. This article reviews the embryologic,
      clinical, pathologic, and imaging features of biliary cystic disease.

PMID- 14647129
TI  - Overview of stress echocardiography: uses, advantages, and limitations.

PMID- 14647130
TI  - Surgical options in young adults with aortic valve disease.

PMID- 14647131
TI  - Anorectal melanoma: surgical management guidelines according to tumour thickness.
AB  - Management of patients with anorectal melanoma is still controversial. To reach a
      rationale therapeutic approach, we reviewed our experience obtained over the past
      decade. In all, 19 consecutive patients with the diagnosis of anorectal melanoma
      were included in this retrospective survey. Details of the patients'
      presentation, symptoms, tumour size and histology and tumour state were recorded,
      and the primary therapeutic procedures were evaluated in detail. The size of the
      tumours ranged between 0.5 and 7 cm in diameter. The median tumour thickness was
      10 mm (range 0.6-40 mm). At diagnosis, six of 19 patients already presented with
      either regional or distant metastases. The remaining 13 patients were treated
      with curative intend, either by abdomino-perineal resection (APR) or wide local
      excision (WLE). The form of operative therapy, however, had no impact on overall
      survival. Nevertheless, the incidence of local recurrences was lower after APR
      even for patients with less favourable tumours. In conclusion, WLE alone is not
      sufficient for local tumour control of thick anorectal melanoma.

PMID- 14647132
TI  - Impact of peritoneal cytology on survival of endometrial cancer patients treated
      with surgery and radiotherapy.
AB  - Stage IIIA endometrial cancer includes patients with serosal or adnexal invasion
      and patients with positive peritoneal cytology only. In this study, we assessed
      the impact of peritoneal cytology on endometrial cancer survival. All endometrial
      cancer patients receiving surgery and radiotherapy at the Geneva University
      Hospitals between 1980 and 1993 were included. Stage IIIA cancers were
      categorised into 'cytological' stage IIIA (only positive peritoneal cytology) and
      'histological' stage IIIA (serosal or adnexal infiltration). Survival rates were
      analysed by Kaplan-Meier method and compared using log-rank test. The prognostic
      importance of peritoneal cytology was analysed by multivariate regression
      analysis. This study included 170 endometrial cancers (112 stage I, 17
      cytological stage IIIA, 18 histological stage IIIA, 9 stage IIIB+). Disease
      specific survival of cytological stage IIIA was not different from stage I (94 vs
      88% respectively, P=0.5) but better than histological stage IIIA (94 vs 51%
      respectively, P<0.01). Histological stage IIIA patients were at increased risk to
      die from cancer compared to stage I patients (HR 2.7, 95% CI 1.0-7.7), while
      cytological stage IIIA patients were not (HR 0.3, 95% CI 0.3-2.0). Cytological
      stage IIIA endometrial cancer has similar prognosis as stage l and better
      prognosis than histological stage IIIA. Additional research, definitively
      separating stage and cytology is warranted.

PMID- 14647133
TI  - Comparison of sustained-release morphine with sustained-release oxycodone in
      advanced cancer patients.
AB  - The antinociceptive effect of morphine and oxycodone is mediated preferentially
      at micro and kappa receptors, respectively. The aim of this study was to evaluate
      the analgesic profile of the combination of morphine and oxycodone in cancer
      pain, compared to the standard administration of morphine alone. Controlled
      release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26
      patients. The study started with an open-label, randomised titration phase to
      achieve stable pain control for 7 days, followed by a double-blind, randomised
      crossover phase in two periods, 14 days each. At any point, patients were allowed
      to use oral immediate-release morphine (IRM) as needed, in order to keep visual
      analogue scale < or =4. Pain, satisfaction, adverse effects and number of daily
      rescue morphine tablets were assessed. A total of 22 patients were evaluated. The
      weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 (1.80, 1.83,
      1.76, 1.84). The weekly IRM consumption was higher in patients having CRM
      compared to patients having CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7)
      (P<0.05). Patients receiving oxycodone complained of less nausea and vomiting.
      The rescue morphine analgesic consumption was 38% higher in patients receiving
      only morphine, compared to patients receiving both morphine and oxycodone. The
      results suggest that the combination of morphine/oxycodone (opioids with
      differential preferential sites of action) can be a useful alternative to
      morphine alone, resulting in a better analgesia profile and less emesis.

PMID- 14647134
TI  - Bone resorption predicts for skeletal complications in metastatic bone disease.
AB  - Relationships between the rate of bone resorption (measured by urinary N
      telopeptide (Ntx) excretion) and a range of skeletal complications have been
      evaluated in patients with metastatic bone disease. A total of 121 patients had
      monthly measurements of Ntx during treatment with bisphosphonates. All skeletal
      related events, plus hospital admissions for bone pain and death during the
      period of observation, were recorded. Data were available for 121 patients over
      the first 3-month period of monitoring (0-3 months) and 95 patients over the
      second 3-month period (4-6 months). N-telopeptide levels were correlated with the
      number of skeletal-related events and/or death (r=0.62, P<0.001 for 0-3 months
      and r=0.46, P<0.001 for 4-6 months, respectively). Patients with baseline Ntx
      values > or =100 nmol mmol(-1) creatinine (representing clearly accelerated bone
      resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a
      skeletal-related event/death during the first 3 months than those with Ntx <100
      (P<0.001). In a multivariate logistic regression model, Ntx was highly predictive
      for events/death. This study is the first to indicate a strong correlation
      between the rate of bone resorption and the frequency of skeletal complications
      in metastatic bone disease. N-telopeptide appears useful in the prediction of
      patients most likely to experience skeletal complications and thus benefit from
      bisphosphonate treatment.

PMID- 14647135
TI  - Neuropsychological outcome in children with optic pathway tumours when first-line
      treatment is chemotherapy.
AB  - Standard treatment of optic pathways gliomas consists of radiotherapy and surgery
      when feasible. Owing to the toxicity of irradiation, chemotherapy has emerged as
      an interesting therapeutic option, especially in young children. This study
      describes the neuropsychological profile of 27 children (aged between 1.5 and
      15.7 years) with optic pathways gliomas treated with chemotherapy as first-line
      treatment. Eight of them also received radiotherapy as salvage treatment. Eight
      had neurofibromatosis type 1 (NF1). Intellectual outcome was preserved in
      children treated with chemotherapy only (mean=107+/-17) compared to children also
      receiving radiotherapy (mean IQ=88+/-24) or children having NF1 and treated with
      chemotherapy (mean IQ=80+/-13). Scores for abstract reasoning, mental arithmetic,
      chessboard/coding, perception, judgement of line orientation were lower in
      children irradiated than in those treated only by chemotherapy. Children with Nf1
      showed subnormal IQ scores with marked impairment of short- and long-term memory.
      With respect to long-term neuropsychological outcome, our study shows that a
      chemotherapy-first strategy can preserve the intellectual outcome of these
      patients either by avoiding the need of radiotherapy or by delaying its use as
      much as possible.

PMID- 14647136
TI  - Prognostic factors for survival in patients with advanced oesophageal cancer
      treated with cisplatin-based combination chemotherapy.
AB  - The objective of this study was to identify prognostic factors for survival in
      patients with advanced oesophageal cancer, who are treated with cisplatin-based
      combination chemotherapy. We analysed the baseline characteristics of 350
      patients who were treated in six consecutive prospective trials with one of the
      following regimens: cisplatin/etoposide, cisplatin/etoposide/5-fluorouracil,
      cisplatin/paclitaxel (weekly) and cisplatin/paclitaxel (biweekly). Predictive
      factors in univariate analyses were further evaluated using multivariate analysis
      (Cox regression). The median survival of all patients was 9 months. The 1, 2 and
      5-year survival rates were 33, 12 and 4%, respectively. The main prognostic
      factors were found to be WHO performance status (0 or 1 vs 2), lactate
      dehydrogenase (normal vs elevated), extent of disease (limited disease defined as
      locoregional irresectable disease or lymph node metastases confined to either the
      supraclavicular or celiac region vs extensively disseminated disease) in addition
      to the type of treatment (weekly or biweekly cisplatin/paclitaxel regimen vs 4
      weekly cisplatin/etoposide with or without 5-fluorouracil). Although weight loss,
      liver metastases and alkaline phosphatase were significant prognostic factors in
      univariate analyses, these factors lost their significance in multivariate
      analyses. The median survival for patients without any risk factors was 12
      months, compared to only 4 months in patients with WHO 2 plus elevated LDH and
      extensive disease. The performance status, extent of disease, LDH and the
      addition of paclitaxel to cisplatin are independent prognostic factors in
      patients with advanced oesophageal cancer, who are treated with cisplatin-based
      combination chemotherapy.

PMID- 14647137
TI  - Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with
      bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose
      escalation study.
AB  - The aim of this study was to define the maximum tolerated dose (MTD) of bolus
      mitomycin C (MMC) in combination with 24 h-continuous infusion of 5-flourouracil
      (FU) plus folinic acid, and to assess the toxicity and activity in patients with
      previously treated colorectal and gastric cancer. Escalating doses of MMC
      starting from 6 mg m(-2) in 2 mg m(-2)-steps to a maximum of 10 mg m(-2) were
      applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m(-2)) as 24 h
      infusion and folinic acid 500 mg m(-2) prior to 5-FU weekly for 6 weeks. At least
      three patients were treated at each dose level. A total of 16 patients have been
      included in the phase I study. At the highest dose level (MMC 10 mg m(-2)), grade
      III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one
      patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer
      and 12 with gastric cancer, 23 patients after failure of first- and 22 patients
      after at least second-line or subsequent chemotherapy have been treated. Seven
      partial responses (PR) were registered (16%), one (3%; CI(95%), 0-16) in
      colorectal and six (50%; CI(95%), 21-79%) in gastric cancer patients. In all, 17
      (38%) achieved disease stabilisation, 15 colorectal (45%, CI(95%), 28-64%) and
      two gastric cancer patients (17%; CI(95%), 2-48%). The median progression-free
      survival was 3.1 months (range, 0.9-9.1) in colorectal and 4.6 months (range, 0.7
      12.4) in gastric cancer. The median overall survival time was 6.6 months (range,
      1.9-15.6) in colorectal and 7.1 months (range, 1.7-20.8) in patients with gastric
      cancer. This regimen was considered to be safe and well tolerated for pretreated
      patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus
      infusional 5-FU/folinic acid may be a potential second-line regimen with
      promising antitumour activity.

PMID- 14647138
TI  - Anal canal cancer treatment: practical limitations of routine prescription of
      concurrent chemotherapy and radiotherapy.
AB  - This study is an analysis of the criteria considered when prescribing concomitant
      chemotherapy and radiotherapy, as a routine treatment for patients with anal
      canal cancer, and related complications. Between 1990 and 1996, 67 patients were
      treated at Institut Curie for invasive, nonmetastatic cancer of the anal canal.
      Median age was 65 years (range, 35-90 years). TNM stage distribution was as
      follows: seven T1, 17 T2, 27 T3, 16 T4, and 22 N+ patients. A total of 29
      patients (i.e., five T1/T2, and 24 T3/T4) received concurrent chemotherapy and
      radiotherapy. Radiotherapy volumes and dose and prescribed dose for chemotherapy
      were not statistically different from one group of patients to another. Only 55%
      of T3/T4 patients underwent standard chemoradiation treatment for anal canal
      cancer. Age was the one of main factor in determining if the patient would
      undergo concomitant chemotherapy or not. For the T3/T4 patients, concomitant
      chemotherapy was prescribed to 69% of patients <55 years, 90% of patients between
      56 and 64 years, 45% of patients between 65 and 75 years, and 20% of patients
      over 75 years (P<0.02). Overall survival at 4 years was 66%. The 4 years overall
      survival rate of T3/T4 patients, who underwent concomitant chemotherapy, was 72%,
      and that of T3/T4 patient who did not, was 34% (P<0.04). The patients who did not
      undergo chemotherapy were significantly older. The difference in cause-specific
      survival rates (72 vs 48%) was not significant. Relapse-free interval without
      local recurrence at 4 years was 70%. Relapse-free interval of T3/T4 patients was
      78% with chemotherapy and 60% without chemotherapy (p=NS). Rates of treatment
      discontinuation and early toxicity were not statistically different. Late
      complications occurred in 33 patients, eight of whom had grade 2/3 tumours. At 2
      years, complications occurred in 39% of patients who had undergone concomitant
      chemotherapy, and in 20% of patients who had not (p<0.02). Differences in grade
      2/3 complications were not significant. In conclusion, although radiotherapy with
      concomitant chemotherapy is considered the current 'gold-standard' treatment for
      anal canal cancer, in our daily experience, only 55% of our T3/T4 patients have
      undergone this treatment. The remainder did not undergo chemotherapy mainly
      because they were deemed too old. In this series, no increase in local control
      and cause-specific survival was observed in patients who received concomitant
      chemotherapy; this may be due to the small number of patients included in the
      series. The increased rate of late complications observed in patients who
      received the combined treatment, however, provides evidence that this treatment
      should be restricted to younger patients without comorbidity and therefore
      justifies our position. Perhaps reduction of doses of chemotherapy must be
      discussed for older patients.

PMID- 14647139
TI  - Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of
      primary breast cancer patients.
AB  - The UK audit was undertaken in primary breast cancer patients receiving adjuvant
      chemotherapy to: (1) record the incidence of neutropenic events (hospitalisation
      due to febrile neutropenia, dose delay of > or =1 week or dose reduction of > or
      =15% due to neutropenia); (2) evaluate the impact of neutropenic events on
      overall dose intensity (DI) received and (3) review the use of granulocyte colony
      stimulating factor (G-CSF) in clinical practice. Data from 422 patients with
      Stage I-III breast cancer were collected from 15 centres. Cyclophosphamide,
      methotrexate and 5-fluorouracil(CMF)- or anthracycline-based regimens were the
      most commonly used. Only 5.2% of patients received G-CSF. Overall, 29% of
      patients experienced a neutropenic event, most frequently dose delay. Neutropenic
      events had a significant impact on the ability to deliver planned DI. Out of 422
      patients, 17% did not achieve 85% of their planned DI; due to neutropenia in 11%
      of patients. Of the neutropenic patients receiving CMF- or anthracycline-based
      regimens, around 40 and 32% of patients, respectively, did not achieve 85% of
      their planned DI. Patients who experienced one neutropenic event had a higher
      risk of a second event. During adjuvant chemotherapy of primary breast cancer,
      neutropenic events are common, likely to occur in subsequent chemotherapy cycles,
      and have a significant impact on receiving planned DI.

PMID- 14647140
TI  - Asking questions can help: development and preliminary evaluation of a question
      prompt list for palliative care patients.
AB  - Question prompt lists (QPLs) have been shown to be an inexpensive and effective
      communication tool for patients in oncology consultations. We aimed to develop
      and pilot a QPL for palliative care (PC) patients. In order to identify suitable
      questions for inclusion in the QPL, we conducted focus groups and individual
      interviews with 19 patients, 24 carers and 22 PC health professionals. A further
      21 health professionals reviewed the draft document. The draft QPL was piloted in
      23 patients. In total, 112 questions were identified and grouped into eight
      categories. All participants felt that the QPL, in booklet form, could be a
      useful tool. Out of 23 patients in the pilot study, 22 agreed that the QPL was
      helpful, contained useful questions, was easy to understand and would be useful
      in the future. State anxiety (STAI) decreased after receiving the booklet and
      seeing the doctor in 16 out of 19 patients (overall anxiety decreased by a median
      of 8, IQR 1-13). Participants in the pilot study endorsed the inclusion of end-of
      life issues in the QPL, despite some reservations expressed about this by health
      professionals in the individual interviews. We have identified a specific QPL
      that might facilitate useful dialogue between PC patients and their doctor. The
      QPL has strong support from patients, their carers and relevant health
      professionals.

PMID- 14647141
TI  - Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in
      women aged 20-44 years: the UK National Case-Control Study of Cervical Cancer.
AB  - We report results on risk factors for invasive squamous cell and adenocarcinomas
      of the cervix in women aged 20-44 years from the UK National Case-Control Study
      of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with
      squamous cell carcinoma and 923 population controls. The risk of both squamous
      cell and adenocarcinoma was strongly related to the lifetime number of sexual
      partners, and, independently, to age at first intercourse. The risk of both types
      of cervical cancer increased with increasing duration of use of oral
      contraceptives, and this effect was most marked in current and recent users of
      oral contraceptives. The risk of squamous cell carcinoma was associated with high
      parity and the risk of both squamous cell and adenocarcinoma increased with early
      age at first birth. Long duration smoking (20 or more years) was associated with
      a two-fold increase in the risk of squamous cell carcinoma, but smoking was not
      associated with the risk of adenocarcinoma. Further studies are needed to confirm
      the suggestion from this and other studies of differences in risk related to
      smoking between squamous cell and adenocarcinomas of the cervix.

PMID- 14647142
TI  - Cigarette smoking and risk of non-Hodgkin lymphoma subtypes among women.
AB  - Previous studies of the relationship between cigarette smoking and non-Hodgkin
      lymphoma (NHL) have yielded conflicting results, perhaps because most studies
      have evaluated the risk for all NHL subtypes combined. Data from a population
      based case-control study conducted among women in Connecticut were used to
      evaluate the impact of cigarette smoking on the risk of NHL by histologic type,
      tumour grade, and immunologic type. A total of 601 histologically confirmed,
      incident cases of NHL and 718 population-based controls provided in-person
      interviews. A standardised, structured questionnaire was used to collect
      information on each subject's current smoking status, age at initiation, duration
      and intensity of smoking, and cumulative lifetime exposure to smoking. Our data
      suggest that cigarette smoking does not alter the risk of all NHL subtypes
      combined. However, increased risk of follicular lymphoma appears to be associated
      with increased intensity and duration of smoking, and cumulative lifetime
      exposure to smoking. Compared with nonsmokers, women with a cumulative lifetime
      exposure of 16-33 pack-years and 34 pack-years or greater experience 50%
      increased risk (OR=1.5, 95% CI 0.9-2.5) and 80% increased risk (OR=1.8, 95% CI
      1.1-3.2), respectively, of follicular lymphoma (P for linear trend=0.05). Our
      study findings are consistent with several previous epidemiologic studies
      suggesting that cigarette smoking increases the risk of follicular lymphoma. This
      research highlights the importance of distinguishing between NHL subtypes in
      future research on the aetiology of NHL.

PMID- 14647143
TI  - The Ki67 index a prognostic marker in medullary thyroid carcinoma.
AB  - Our objective was to examine the usefulness of the Ki67 proliferation index as a
      prognostic marker in patients with medullary thyroid carcinoma (MTC). It is
      difficult to predict the prognosis of MTC by using conventional prognostic
      factors. Immunocytochemical analysis of tumour proliferation has been used as a
      prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from
      36 patients were investigated, by using a semiautomatic image analysis programme.
      On average 10,000 nuclear profiles were counted per tumour, and the percentage of
      tumour cells expressing the proliferation marker, Ki67, was calculated. Primary
      tumours that had metastasised had higher Ki67 indices than primary tumours that
      had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices
      than the primary tumours. By using a Poisson model, it was possible to estimate
      the median survival time for individual patients if the Ki67 index for the
      primary tumour and the age at surgery were known. The higher the Ki67 index and
      the age at operation were, the shorter was the survival. Estimating the median
      survival of individual patients will be of help for planning the patients' life
      and postoperative follow-up and treatment.

PMID- 14647144
TI  - Histological validation of diagnoses of thyroid cancer among adults in the
      registries of Belarus and the Ukraine.
AB  - In order to evaluate the diagnostic reliability of the thyroid cancers listed in
      adult registries from the Ukraine and Belarus, a histological review was
      organised of 327 randomly selected thyroid carcinoma cases diagnosed between 1980
      and 1999. A final diagnosis was reached at a 5-day consensus conference by six
      pathologists who met around a multiheaded microscope. The study concluded with a
      comparison between the final diagnosis and the initial diagnosis. The
      pathologists agreed with the initial diagnosis of malignancy in 286 cases (88%).
      A final diagnosis of papillary, follicular or medullary thyroid carcinoma was
      reached in 86, 4, and 6% of the cases respectively. In 2.8% of the cases
      reviewed, diagnostic discrepancies persisted. The percentage of agreement between
      the final diagnosis and the initial diagnosis was 93%, with a weighted kappa
      statistic of 0.61 (confidence interval 95% (CI(95%)): [0.45-0.77]). In all, 89%
      of the 286 confirmed cancer cases were in agreement for the type of cancer, with
      a kappa-statistic of 0.56 (CI(95%): [0.43-0.69]). The level of agreement differed
      according to cancer categories, with concordance rates of 94, 40 and 33% for
      papillary, follicular and medullary thyroid carcinomas respectively. The low
      prevalence of follicular thyroid carcinomas in the adult population studied calls
      for further exploration. The discrepancies and classification difficulties
      encountered were analysed.

PMID- 14647145
TI  - An increased high-mobility group A2 expression level is associated with malignant
      phenotype in pancreatic exocrine tissue.
AB  - The altered form of the high-mobility group A2 (HMGA2) gene is somehow related to
      the generation of human benign and malignant tumours of mesenchymal origin.
      However, only a few data on the expression of HMGA2 in malignant tumour
      originating from epithelial tissue are available. In this study, we examined the
      HMGA2 expression level in pancreatic carcinoma, and investigated whether
      alterations in the HMGA2 expression level are associated with a malignant
      phenotype in pancreatic tissue. High-mobility group A2 mRNA and protein
      expression was determined in eight surgically resected specimens of non
      neoplastic tissue (six specimens of normal pancreatic tissue and two of chronic
      pancreatitis tissue) and 27 pancreatic carcinomas by highly sensitive reverse
      transcriptase-polymerase chain reaction (RT-PCR) techniques and
      immunohistochemical staining, respectively. Reverse transcriptase-polymerase
      chain reaction analysis revealed the expression of the HMGA2 gene in non
      neoplastic pancreatic tissue, although its expression level was significantly
      lower than that in carcinoma. Immunohistochemical analysis indicated that the
      presence of the HMGA2 gene in non-neoplastic pancreatic tissue observed in RT-PCR
      reflects its abundant expression in islet cells, together with its focal
      expression in duct epithelial cells. Intense and multifocal or diffuse HMGA2
      immunoreactivity was noted in all the pancreatic carcinoma examined. A strong
      correlation between HMGA2 overexpression and the diagnosis of carcinoma was
      statistically verified. Based on these findings, we propose that an increased
      expression level of the HMGA2 protein is closely associated with the malignant
      phenotype in the pancreatic exocrine system, and accordingly, HMGA2 could serve
      as a potential diagnostic molecular marker for distinguishing pancreatic
      malignant cells from non-neoplastic pancreatic exocrine cells.

PMID- 14647146
TI  - Incidence, mechanism and prognostic value of activated AKT in pancreas cancer.
AB  - When activated, the serine/threonine kinase AKT mediates an antiapoptotic signal
      implicated in chemoresistance of various cancers. The mechanism(s) of AKT
      activation are unknown, though overexpression of HER-2/neu has been implicated in
      breast cancer. Therefore, we determined the incidence of activated AKT in human
      pancreatic cancer, whether HER-2/neu is involved in AKT activation, and if AKT
      activation is associated with biologic behaviour. HER-2/neu expression and AKT
      activation were examined in seven pancreatic cancer cell lines by Western
      blotting. The in vitro effect of HER-2/neu inhibition on AKT activation was
      similarly determined. Finally, 78 pancreatic cancer specimens were examined for
      AKT activation and HER-2/neu overexpression, and correlated with the clinical
      prognostic variable of histologic grade. HER-2/neu was overexpressed in two of
      seven cell lines; these two cell lines demonstrated the highest level of AKT
      activation. Inhibition of HER-2/neu reduced AKT activation in vitro. AKT was
      activated in 46 out of 78 (59%) of the pancreatic cancers; HER-2/neu
      overexpression correlated with AKT activation (P=0.015). Furthermore, AKT
      activation was correlated with higher histologic tumour grade (P=0.047). Thus, it
      is concluded that AKT is frequently activated in pancreatic cancer; this
      antiapoptotic signal may be mediated by HER-2/neu overexpression. AKT activation
      is associated with tumour grade, an important prognostic factor.

PMID- 14647147
TI  - Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with
      unfavourable prognosis in superficial oesophageal cancer.
AB  - If oesophageal carcinoma is detected in the superficial stage, the prognosis is
      better than for advanced oesophageal carcinoma. But the factors which predict the
      prognosis and treatment policy remain unclear. Matrix metalloproteinase-7 (MMP-7)
      and matrix metalloproteinase-9 (MMP-9) have been reported to have close
      associations with tumour invasion and metastasis. In this study, we
      retrospectively studied the relations between MMP-7 and MMP-9 expression in
      immunohistochemistry, clinicopathologic factors, and prognosis in 55 superficial
      oesophageal carcinomas. MMP-7 and MMP-9 expression occurred in 23.6% and 47.3% of
      the patients, respectively. MMP-7 expression was significantly correlated with
      the presence of nodal metastasis (P=0.004). MMP-9 expression was significantly
      correlated with the depth of tumour invasion (P=0.004), lymphatic permeation
      (P=0.001), nodal metastasis (P=0.049), and pathologic differentiation grade
      (P=0.003). By the log-rank test, MMP-7 expression and MMP-9 expression on the
      invasive front were related to the prognosis. In multivariate analysis, MMP-9
      expression on the invasive front was an independent prognostic indicator. The
      combined expression of MMP-7 and MMP-9 may be a good marker for the degree of
      malignancy of oesophageal cancer and for the presence of lymphatic metastasis.

PMID- 14647148
TI  - Irradiation differentially affects substratum-dependent survival, adhesion, and
      invasion of glioblastoma cell lines.
AB  - Effects of ionising radiation on extracellular matrix (ECM)-modulated cell
      survival and on adhesion and invasion are not well understood. In particular, the
      aggressiveness of glioblastoma multiforme has been associated with tumour cell
      invasion into adjacent normal brain tissue. To examine these effects in more
      depth, four human glioblastoma cell lines (A-172, U-138, LN-229 and LN-18) were
      irradiated on fibronectin (FN), Matrigel, BSA or polystyrene. Major findings of
      this study include a significantly increased survival of irradiated A-172 but not
      of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells
      irradiated on polystyrene or BSA. Irradiation induced a dose-dependent increase
      in functional beta 1- and beta 3-integrins in all four glioma cell lines. This
      integrin induction caused improved cell adhesion to FN or Matrigel. In contrast
      to U-138, LN-229 and LN-18 cells, irradiation strongly impaired A-172 cell
      invasion. Invasion of all cell lines was inhibited by anti-integrin antibodies,
      the disintegrin echistatin and the MMP-2/-9 inhibitor III. Additionally, beta 1-
      and beta 3-integrins modulated basal and radiation-altered gelatinolytic activity
      of MMP-2. Tested glioblastoma cell lines showed a differential cellular
      susceptibility to FN or Matrigel which affected the cellular radiosensitivity.
      Three out of four glioma cell lines demonstrated a combination of a substratum
      independent survival after irradiation and an invasive potential which was not
      affected by irradiation. beta 1- and beta 3-integrins were identified to play a
      substantial, regulatory role in survival, adhesion, invasion and MMP-2 activity.
      Detailed insights into radioresistance and invasion processes might offer new
      therapeutic strategies to enhance cell killing of lethal high-grade astrocytoma.

PMID- 14647149
TI  - Efficacy of cytotoxic agents used in the treatment of testicular germ cell
      tumours under normoxic and hypoxic conditions in vitro.
AB  - Platinum-based chemotherapy is the main treatment element to achieve cure for
      patients with metastatic germ cell tumours. Drug resistance in testicular germ
      cell tumours (TGCTs) is rare and the reasons are not fully understood. While
      recent investigations have indicated decreased efficacy of chemotherapy in
      several tumour types under hypoxic conditions, this aspect has not been
      investigated in TGCTs so far. Furthermore, for cisplatin - the most active drug
      in this disease - controversial effects of hypoxia on cytotoxic efficacy have
      been reported. The relative efficacy of cytotoxic agents for the treatment of
      TGCT patients was studied in three different cell lines derived from human
      embryonal carcinomas (EC) in an in vitro hypoxia model. NT2, 2102 EP, and NCCIT
      were tested for their sensitivity towards cisplatin, etoposide, bleomycin, 4-OOH
      ifosfamide, carboplatin, paclitaxel, gemcitabine, oxaliplatin, irinotecan, and
      mitomycin C under normoxic and hypoxic conditions using the MTT assay. Inhibitory
      concentrations IC(50) of the tested agents under both conditions were compared.
      Selected results were confirmed by flow-cytometric assessment of the apoptotic
      index. In all cells, doubling times were prolonged in hypoxia (NT2<NCCIT<2102
      EP). All drugs were less effective under hypoxic conditions, including mitomycin
      C (eg, 1.6-fold increase of IC(50) in hypoxia compared to normoxia for NT2) and
      cisplatin (eg, NT2: two-fold increase). The relative effect of hypoxia on the
      IC(50) depended mainly on the cell line, and to a lesser extent on the drug. The
      results indicate that the reduced cell proliferation in hypoxia might be an
      important factor, but not the only determinant of a reduced cytotoxicity. In view
      of the broad spectrum of drugs with different modes of action tested, the
      relative resistance cannot be mediated by substance-specific resistance
      mechanisms like hypoxia-induced upregulation of P-glycoprotein or increased DNA
      repair capacity, since many unrelated drugs were affected to a comparable extent
      in their efficacy by hypoxia. This study also provides the rationale to test the
      hypothesis whether improving tumour oxygenation by raising haemoglobin
      concentrations, for example, with erythropoietin in patients with TGCTs receiving
      chemotherapy may improve the outcome.

PMID- 14647150
TI  - A comparative study between catalase gene therapy and the cardioprotector
      monohydroxyethylrutoside (MonoHER) in protecting against doxorubicin-induced
      cardiotoxicity in vitro.
AB  - Cardiotoxicity is the main dose-limiting side effect of doxorubicin in the
      clinic. Being a free radical producer, doxorubicin affects the heart specifically
      because of its low antioxidant capacity. Among those antioxidants, catalase is
      present in very low levels in the heart compared to other organs. Since catalase
      is an essential enzyme in detoxifying hydrogen peroxide, the aim of the present
      study was to investigate the protective effect of catalase as delivered by an
      adenovirus vector against doxorubicin-induced cardiotoxicity in cultured neonatal
      rat cardiac myocytes (NeRCaMs). 7-Monohydroxyethylrutoside (MonoHER), a potent
      cardioprotector currently under clinical investigations, was included in the
      study as a reference. Neonatal rat cardiac myocytes were infected with different
      multiplicity of infections (MOIs) of adenovirus encoding catalase (AdCat). A
      control infection with an adenovirus vector encoding a nonrelated protein was
      included. The activity and content of catalase in infected cells were determined
      during 3 days postinfection. One group of NeRCaMs was infected with AdCat before
      treatment with doxorubicin (0-50 microM). The second and third group were treated
      with doxorubicin (0-50 microM) with and without 1 mM monohydroxyethylrutoside
      (monoHER), respectively. The LDH release and viability of treated cells were
      measured 24 and 48 h after doxorubicin treatment. The beating rate was followed
      in three other groups of cells receiving the same treatments within 3 days after
      doxorubicin (0-100 microM) treatment. Catalase activity increased in AdCat
      infected cells, with different MOIs, starting from the second day after infection
      as compared to the mock-infected cells (P<0.03). At the third day of infection,
      an MOI of more than 50 caused cytopathic effects, which hampered the use of
      higher viral titres. With an MOI of 50, catalase activity increased 3.5-fold in
      AdCat-infected cells 3 days postinfection (P=0.021) compared to mock-infected
      cells. The beating rate and survival of NeRCaMs decreased in a concentration and
      time-dependent manner after doxorubicin treatment (P<0.0005). This cytotoxicity
      was associated with an increase in the LDH release from the treated cells
      (P<0.0005). The cells stopped beating 24 h after treatment with >50 microM
      doxorubicin. A 3.5-fold increase in the activity of catalase did not protect
      NeRCaMs against any of the cytotoxic effects of doxorubicin on NeRCaMs. In
      contrast, monoHER (1 mM) significantly protected NeRCaMs against the lethal
      effects of doxorubicin on the survival, LDH release and the beating rate of
      NeRCaMs (P<0.004) during 48 h after doxorubicin treatment. This protection
      resulted in a prolongation of the beating of doxorubicin-treated cells after the
      end of the experiment (i.e. >72 h). The present study (1) illustrates that the
      cytotoxicity of high MOI of AdCat (>50) limited the possibility to increase
      catalase activity more than 3.5-fold, which was not enough to protect infected
      NeRCaMs against doxorubicin-induced cardiotoxicity and (2) confirms the efficacy
      of monoHER as a cardioprotector. Thus, the use of monoHER proves more suitable
      for the prevention of doxorubicin-induced cardiotoxicity than catalase gene
      transfer employing adenovirus vectors.

PMID- 14647151
TI  - Functional evaluation of the apoptosome in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) responds very poorly to chemo- or radiotherapy. Renal
      cell carcinoma cell lines have been described to be resistant to apoptosis
      inducing stimuli and to lack caspase expression. Here, we provide a structural
      and functional assessment of the apoptosome, the central caspase-activating
      signalling complex and a candidate for apoptosis-inactivating mutations. Cells
      from RCC cell lines and clinical samples isolated from RCC patients were
      included. Apoptosome function was measured as quantitative activation of caspases
      in protein extracts. In all five cell lines and in 19 out of 20 primary clear
      cell RCC samples, the expression of apoptosome components and caspase activation
      appeared normal. Of the four nonclear cell RCC that could be included, both
      oncocytomas gave no response to cytochrome c (in one case, no Apaf-1 was
      detected), one chromophobe RCC lacked caspase-9 and failed to activate caspase-3
      in response to cytochrome c, and one papillary RCC showed good caspase activation
      despite the lack of caspase-7. Experiments utilising a peptide derived from
      Smac/DIABLO gave no indication that inhibitor of apoptosis proteins might exert
      an inhibiting effect in primary clear cell RCC. Thus, the apoptosome signalling
      complex is intact in human (clear cell) RCC, and an apoptosis defect must be
      located at other, probably upstream, sites.

PMID- 14647154
TI  - Half-full or half-empty.

PMID- 14647152
TI  - Induction of apoptosis in experimental human B cell lymphomas by conditional
      TRAIL-expressing T cells.
AB  - In the present study, we demonstrate the utility of a non-tumour-forming T-cell
      line for the inducible gene transfer of tumour necrosis factor (TNF)-related
      apoptosis-inducing ligand (Apo2L/TRAIL), which has been shown to selectively
      induce apoptosis in malignant but not in normal cells. To generate T cells
      inducible for TRAIL expression, we stably transfected Jurkat cells with TRAIL in
      the context of the Tet-On system. The switched on cells strongly expressed TRAIL
      mRNA, whose protein product was expressed on the cell surface. Paracrine
      induction of apoptosis in human target tumour cells was solely found for membrane
      bound TRAIL. The Jurkat-TRAIL cells itself survived due to clonal selection of
      TRAIL-resistant cells. Jurkat-TRAIL cells had an additive effect with cytotoxic
      drugs in vitro, since cell death was enhanced. To elucidate the antitumoral
      activity of these Jurkat-TRAIL cells in vivo, we injected them intratumorally in
      xenografts of human Burkitt lymphomas. Switching on expression of TRAIL by adding
      tetracycline to the drinking water of the mice strongly reduced tumour growth by
      apoptosis in a caspase-dependent manner. Thus, non-tumour-forming T-cell lines
      offer a novel method for gene transfer and inducible expression of TRAIL in
      tumour therapy.

PMID- 14647155
TI  - Local health department perspectives on linkages among birthing hospitals.
AB  - OBJECTIVES: To describe perinatal linkages among hospitals, changes in their
      numbers and their impact on relationships among high-risk providers in local
      communities. STUDY DESIGN: Data were obtained about the organization of perinatal
      services in 1996-1999 from a cross-sectional study evaluating fetal and infant
      mortality review (FIMR) programs nationwide. Geographic areas were sampled based
      on region, population density, and the presence of a FIMR. A local health
      department representative was interviewed in 76% (N=193) of eligible communities;
      188 provided data about hospitals. RESULTS: Linkages among all hospitals were
      reported in 143 communities and with a subspecialty hospital in 122. All but 12
      communities had a maternity hospital, and changes in the number of hospitals
      occurred in 49 communities. Decreases in the number of Level II hospitals were
      related to changes in relationships among providers of high-risk care for mothers
      and newborns; they were associated with changing relationships only for mothers
      in Level I hospitals. These relations were noted only where established provider
      relationships existed. CONCLUSIONS: Decreases in the number of maternity
      hospitals affect provider relationships in communities, but only where there are
      established linkages among hospitals.

PMID- 14647156
TI  - Effects of powdered human milk fortifiers on the antibacterial actions of human
      milk.
AB  - OBJECTIVES: To evaluate the effects of powdered fortifiers and the addition of
      iron and medium-chain triglycerides on preterm human milk antibacterial activity.
      STUDY DESIGN: Human milk samples were obtained from 42 preterm lactating mothers
      after the first week of postnatal life. Enfamil (EHMF) and Similac (SHMF) Human
      Milk Fortifiers were evaluated. All mothers were healthy and were on no
      medications except for vitamins during lactation. The effects of each fortifier
      against E. coli (E. coli), Staphylococcus (Staph), Enterobacter sakazakii (ES),
      and Group B Streptococcus (GBS) were measured by the filter paper method and
      growth of the bacteria with human milk alone as control. The addition of iron and
      medium-chain triglycerides (MCT) to human milk was also tested. RESULTS: Human
      milk inhibited the growth of E. coli, Staph, ES, and GBS. Only the SHMF and the
      addition of MCT had similar antibacterial action as human milk alone. EHMF and
      the addition of iron to human milk removed the milk's antibacterial action
      against these four organisms. CONCLUSIONS: Preterm human milk has antimicrobial
      activity against E. coli, Staph, ES, and GBS. This activity can be affected by
      the addition of iron and fortifiers that contain iron.

PMID- 14647157
TI  - Comparison of breast- and formula-fed normal newborns in time to first stool and
      urine.
AB  - BACKGROUND: Although the time to an infant's first stool is used as a marker for
      a normal GI tract, there have been no studies to date which have evaluated the
      contribution of the first 24 hours' feeding type to time to first meconium stool,
      directly comparing breast feeding vs formula feeding. OBJECTIVE: To compare
      breast- and formula-fed healthy infants > or =34 weeks gestation in time to first
      stool and urine. STUDY DESIGN: A chart review of 1000 consecutive infants > or
      =34 weeks of gestational age admitted to the normal newborn nursery of Children's
      Hospital of Buffalo from June to October 2000. Infants (n=979) were grouped based
      on feeding type in the first 24 hours: breast-fed (n=211), formula-fed (n=540),
      and mixed feeding (n=228); n=21 excluded for Neonatal Intensive Care Unit
      admission. We initially compared the time to first stool and urine between the
      breast- and formula-fed groups and then examined multiple maternal and infant
      demographic and clinical factors for their effect on time to first stool using
      univariate and multivariate analyses. RESULTS: Breast-fed infants were fed
      earlier and more frequently than formula-fed but there was no significant
      difference in time to first stool (7.6 vs 7.9 hours). Breast-fed infants were
      earlier in time to first urine (p=0.03) (7.3 vs 8.5 hours). In multiple
      regression analysis, gestational age was the only significant (p=0.000) factor in
      predicting time to first stool. CONCLUSION: Type of feeding did not predict time
      to first stool but gestational age was important even in this near-term and term
      population of infants > or =34 weeks gestation.

PMID- 14647158
TI  - Value of neurosonography in predicting subsequent cognitive and motor development
      in extremely low birth weight neonates.
AB  - OBJECTIVE: To compare the results of neurosonography (NSG) with subsequent
      neurodevelopmental testing in extremely low birth weight (ELBW; < or =1000 g)
      neonates. STUDY DESIGN: NSG at hospital discharge was available in 164 neonates
      and Bayley Scores of Infant Development (BSID II) evaluations (MDI and PDI) were
      performed in 158 of these infants at 18 to 22 months. Neurosonographic studies
      obtained prior to the discharge study also were evaluated. Neurosonograms were
      interpreted by pediatric radiologists, and BSID II examinations were performed by
      certified examiners masked to the results of the neurosonographic studies.
      RESULTS: A normal sonographic study at discharge was observed in 44% (14/32) of
      neonates with MDI <70 and 29% (7/24) with PDI <70. Furthermore, the sonographic
      study at discharge was normal in 59% (36/61) of neonates with MDI 70 to 84 and
      56% (31/55) with PDI 70 to 84. Conversely, approximately 30 to 40% of those with
      an abnormality noted on neurosonogram at discharge, or at any time during
      hospitalization, had MDI and/or PDI scores > or =85. The association between
      abnormal NSG at discharge and low BSID II results was stronger for the PDI exam
      compared with the MDI exam. CONCLUSION: These results emphasize the limitations
      of NSG in predicting subsequent neurodevelopmental outcome in ELBW neonates. The
      primary role for NSG in ELBW neonates may be in the diagnosis and management of
      acute problems, such as intraventricular hemorrhage and posthemorrhagic
      hydrocephalus, and not as a tool to predict subsequent outcome.

PMID- 14647159
TI  - Once-daily gentamicin dosing for the preterm and term newborn: proposal for a
      simple regimen that achieves target levels.
AB  - OBJECTIVE: Based on recent safety and efficacy data, combined with the known
      pharmacokinetic parameters of aminoglycosides in the newborn, once-daily
      gentamicin should be preferable to the many other dosing regimens currently in
      use. Although there are growing data to support its use in term newborns,
      experience with preterm infants is more limited. In our Neonatal Intensive Care
      Unit, we experienced difficulties regarding complicated dosing regimens, actual
      dosing errors, and the tendency to check trough and peak levels around the third
      dose for infants receiving only a 48 hour course. Therefore, we conducted a
      quality improvement initiative in which we developed and tested a clinical
      practice guideline for the use of once-daily gentamicin for preterm and term
      infants that we hoped would yield trough and peak levels in our target range.
      METHODS: We combined a review of the published English language literature with
      pharmacokinetic analysis of our own data prior to initiation of this new regimen
      to design the following dosing regimen: <35 weeks gestation: 3 mg/kg q 24 hours,
      > or =35 weeks gestation: 4 mg/kg q 24 hours. Our goal serum levels were a trough
      < or =2 microg/ml and a peak between 6 and 12 microg/ml. We collected and
      analyzed trough and peak levels from all infants receiving this dosing regimen in
      the first week of life for at least 72 hours between 3/1/99 and 12/31/00.
      RESULTS: In total, 214 babies met our inclusion criteria, 75 of whom were <35
      weeks gestation. 100% of babies of all gestational ages had a nontoxic trough
      level. For infants <35 weeks gestation, 79% had a therapeutic peak level, with a
      mean value of 6.8 microg/ml. For infants of at least 35 weeks gestation, 93% had
      a therapeutic peak level, with a mean value of 8.4 microg/ml. 92% of
      nontherapeutic peaks were too low. CONCLUSION: This study of once-daily
      gentamicin represents the largest sample size of pre-term infants published to
      date. The proposed regimen is simple and yields a high proportion of desirable
      levels. We recommend it for use in preterm and term newborns.

PMID- 14647160
TI  - Preterm infant thermal responses to caregiving differ by incubator control mode.
AB  - OBJECTIVE: To determine the influence of caregiving on preterm infant and
      incubator temperature and to investigate incubator control mode in thermal
      responses to caregiving. STUDY DESIGN: The intensive within-subject design
      involved continuous recording of infant and incubator temperature and videotaping
      throughout a 24-hour period in 40 hospitalized preterm infants. Temperature at
      care onset was compared with care offset, and 5, 10, 15, and 20 minutes following
      care offset using ANOVA-RM. RESULTS: Following caregiving, infant and incubator
      temperature differed significantly over time by incubator control mode. In air
      servo-control, infant temperature tended to decrease after caregiving, while in
      skin servo-control infant temperature remained relatively stable. With
      caregiving, incubator temperature remained consistent in air servo-control and
      increased in skin servo-control. CONCLUSIONS: The temperature effects of
      caregiving should be considered relative to maintenance of thermoneutrality and
      unintentional thermal stimulation.

PMID- 14647161
TI  - Adaptation of kangaroo mother care for community-based application.
AB  - OBJECTIVE: Working with a multidisciplinary team of Ecuadorians, Bangladeshis and
      Americans, we developed a simple protocol for community-based implementation of
      kangaroo mother care (CKMC) that does not require birth weight or clinical
      judgment to identify which newborns should receive CKMC. CKMC could stabilize
      newborns and possibly reduce neonatal mortality where there is little medical
      care for newborns and low birth weight (LBW) is common. STUDY DESIGN: During
      their CKMC training, community-based workers identified 35 expectant or recently
      delivered women in the pilot study area and taught them about CKMC. Women were
      interviewed at 1 month postpartum to evaluate their experience with CKMC.
      RESULTS: In all, 77% of mothers initiated skin-to-skin care and 85% with LBW
      babies did so (37% were LBW). CKMC mothers delayed newborn bathing. Few slept
      upright with their newborns. CONCLUSIONS: CKMC was quickly and popularly adopted.
      A randomized controlled cluster trial is planned to determine whether CKMC
      reduces neonatal mortality.

PMID- 14647162
TI  - Antenatal diagnosis of surgically correctable anomalies: effects of repeated
      consultations on parental anxiety.
AB  - OBJECTIVE: To assess whether or not a correlation exists between antenatal
      consultations and parental anxiety. STUDY DESIGN: In total, 31 couples undergoing
      prenatal consultation after a diagnosis of a surgically correctable anomaly were
      asked to fill in a questionnaire (Spielberger State-Trait Anxiety Inventory)
      measuring anxiety levels (AL) both after the first consultation and at birth.
      Prenatal counselling was done by a perinatal team including paediatric surgeon,
      obstetrician, and psychologist. RESULTS: Malformations were: eight diaphragmatic
      hernias, 10 intestinal atresias, four abdominal masses, nine abdominal wall
      defects. Each fetus was subsequently followed up at regular intervals from
      diagnosis to birth. AL at birth were then compared with the number of antenatal
      consultations. A negative correlation (r=-0.688, p<0.001) was found between the
      number of consultations and the level of anxiety at birth. Patients having at
      least two consultations had significantly lower anxiety levels at birth.
      CONCLUSION: Irrespective of the type of malformation, there is evidence that
      having more than one antenatal consultation may significantly reduce AL at birth.
      Therefore, early antenatal diagnosis should be encouraged in order to increase as
      much as possible chances of repeated consultations for the prospective parents.

PMID- 14647163
TI  - The use of quantitative ultrasound in assessing bone status in newborn preterm
      infants.
AB  - OBJECTIVE: Quantitative ultrasound is increasingly used to assess bone status in
      adults and children; however, few studies have been carried out in neonates. Our
      objective was to determine if tibial bone speed of sound (SOS) correlates with
      gestational age and birth anthropometrics, and if bone SOS is related to maternal
      factors. STUDY DESIGN: We prospectively studied 95 preterm infants to assess
      factors related to bone status as measured by quantitative ultrasound. RESULTS:
      We found significant (p< or =0.001) positive correlations between SOS and
      gestational age, birth weight, length, head circumference and tibial length.
      There was no significant relationship between SOS and prenatal steroid use,
      gestational diabetes, pre-eclampsia, race or parity. CONCLUSIONS: Quantitative
      ultrasound is an easy to use and inexpensive tool for assessing bone status in
      preterm neonates. Tibial SOS correlated with gestational age and birth
      anthropometrics, and was not related by few maternal factors.

PMID- 14647164
TI  - Ten-year trends in neonatal assisted ventilation of very low-birthweight infants.
AB  - OBJECTIVES: To examine ventilatory support for the VLBW infant over the past 10
      years in a single academic NICU and determine factors that predicted length of
      ventilation, death, and CLD. STUDY DESIGN: A retrospective cohort review of
      neonatal blood gases, ventilatory support, and clinical outcomes. RESULTS: From
      1992 through October 2002, 6254 infants were admitted, of whom 2388 required
      intubation for mechanical ventilation. Of these, 837 were <1500 g at birth (VLBW)
      infants and 453 were less than 1000 g (ELBW). Total duration of ventilation
      decreased in all weight groups. Noninvasive ventilatory support increased from 20
      to 55% of total ventilation from 1997 to 2002. During this same period, CLD
      decreased from 20 to 11% in ventilated VLBW infants. Duration of total
      ventilation was best predicted by birth weight, with each 100 g increment
      decreasing the duration of ventilation by 71 hours. Lower birth weight, male sex,
      and a longer total duration of ventilatory support were significant factors in
      predicting the occurrence of CLD. Death alone was best predicted by lower birth
      weight and maximum oxygen index (OI). Transported infants had significantly
      increased maximal OIs, durations of ventilation, and incidence of death. A total
      of 48% of infants with a single OI >10 either died or survived with CLD.
      CONCLUSIONS: Birth weight is the best predictor of duration of ventilation, and
      CLD is best predicted by birth weight, duration of ventilation and male sex. The
      increasing use of noninvasive strategies has not been associated with an
      observable increase in respiratory morbidity. VLBW infants with a single OI>10
      may benefit from inclusion in future interventional rescue studies.

PMID- 14647165
TI  - Development of a scoring system for predicting the risk of preterm birth in women
      receiving cervical cerclage.
AB  - OBJECTIVE: To develop a model for identifying women receiving cervical cerclage
      at risk for spontaneous preterm birth <32 weeks. STUDY DESIGN: Retrospective
      cohort study of high-risk patients based on past obstetric history. Our inclusion
      criteria involved all patients with singleton gestation who received cerclage
      between 10 and 24 weeks. They were evaluated for the risk factors associated with
      preterm birth <32 weeks. Risk factors evaluated include: indication for cerclage,
      gestational age at cerclage placement, cervical length prior to cerclage, timing
      of cerclage (emergency or elective) and route of cerclage (abdominal or vaginal).
      Univariable and multivariable analyses were used to determine the risk factors
      associated with preterm birth. A risk-scoring model was developed for the
      prediction of preterm birth <32 weeks in women receiving cerclage. RESULTS: We
      identified 256 women receiving cerclage that met our inclusion criteria. Preterm
      births <32 weeks occurred in 51 (20%). Multivariable analysis revealed a cervical
      length <25 mm, a history of cone biopsy and emergency cerclage to be significant
      risk factors associated with preterm birth <32 weeks. The sensitivity,
      specificity, positive and negative predictive values of the best model for
      predicting spontaneous preterm birth <32 weeks in women with cerclage are 80%;
      96%; 82% and 95%, respectively. CONCLUSION: The presence of a short cervical
      length, a history of cone biopsy and emergency cerclage were associated with
      preterm birth <32 weeks. Our model had a high sensitivity for identifying women
      who may benefit from a closer surveillance.

PMID- 14647166
TI  - Partial or complete antenatal steroids treatment and neonatal outcome in
      extremely low birth weight infants < or =1000 g: is there a dose-dependent
      effect?
AB  - OBJECTIVES: To assess the outcome of extremely low birth weight (ELBW) infants <
      or =1000 g as it relates to antenatal steroids (ANS) therapy. STUDY DESIGN: A
      retrospective analysis of 124 infants born between January 1995 and December
      1997. Infants born to mothers with pregnancy-induced hypertension, diabetes, and
      severe growth restriction were excluded. In all, 77 (62%) infants were exposed to
      ANS, of whom 31 (25%) received one to two doses (partial course), and 46 (37%)
      received three to four doses (complete course). A total of 47 infants (38%) were
      not exposed to ANS. RESULTS: Infants not exposed to ANS, who exhibited more HMD,
      PDA, and IVH, were administered more surfactants, and were more likely to die
      versus infants with complete ANS dosing. Regression models revealed a dose
      dependent effect of ANS on HMD, surfactant use, IVH, and CLD or death, with a
      significant decrease in HMD with > or =2 ANS doses. CONCLUSIONS: ANS, in a dose
      dependent way, are associated with improved outcome in ELBW infants < or =1000 g,
      with the best outcome seen after a complete course.

PMID- 14647167
TI  - Is retinopathy of prematurity increasing among infants less than 1250 g birth
      weight?
AB  - OBJECTIVE: Retinopathy of prematurity (ROP) is a complication seen in many very
      low birth weight infants. Severe ROP has been called a "marker" for severe
      disability. The purpose of this study was to evaluate the occurrence and severity
      of ROP among infants < or =1250 g birth weight treated in the Special Care
      Nursery at Women & Infants' Hospital over a period of 7 years from 1994 to 2000.
      STUDY DESIGN: This was a retrospective review of ROP data combined with neonatal
      follow-up data. Of the 1002 infants born with birth weights <1250 g,
      ophthalmologic data were available for 739 of 839 survivors. Analysis of variance
      and chi2 along with logistic regression were used to analyze outcomes. RESULTS:
      An increase in the overall occurrence of ROP was identified (40% to 54% linear
      trend, p=0.007). The occurrence of threshold ROP ranged from 2% to 5% (NS).
      Infants at greatest risk of ROP were those micropremies with birth weights <750 g
      (p<0.001). CONCLUSION: Severe ROP continues to be a significant morbidity among
      infants <750 g.

PMID- 14647168
TI  - Recognizing the potential effect of stress and trauma on premature infants in the
      NICU: how are outcomes affected?
AB  - Extensive research of the long-term outcomes of premature infants has shown
      significant risk for emotional, behavioral, and psychological problems. Chronic
      stress and trauma have not been researched specifically in this population,
      however, studies of the neurobiological impact of traumatic stress on infants and
      children in the general population show noteworthy parallels in symptomotology.
      Careful consideration should be given to practitioner caregiving, parent
      education, future research, assessment, and interventions while being mindful of
      the impact that chronic stress and trauma may have on the developing brain of the
      premature infant.

PMID- 14647169
TI  - Primary ciliary dyskinesia as a cause of neonatal respiratory distress:
      implications for the neonatologist.
AB  - We report two cases of term infants who presented with prolonged respiratory
      distress, rhinitis, and situs inversus. A high index of suspicion led to the
      diagnosis of Kartagener Syndrome, which is a subgroup of primary ciliary
      dyskinesia, in the immediate neonatal period.

PMID- 14647170
TI  - An unusual cause of neonatal respiratory distress.
AB  - Nasal cysts representing cystic extension of the nasolacrimal duct are a rare
      cause of nasal obstruction and respiratory distress in neonates. A medial canthal
      mass, epiphora, dacryocystitis or preseptal/orbital cellulitis are the usual
      presenting symptoms; however, this case shows that patients may present with eye
      findings so minimal as to be overlooked.

PMID- 14647171
TI  - Late onset group B streptococcal infection from maternal expressed breast milk in
      a very low birth weight infant.

PMID- 14647172
TI  - Intrauterine cerebral infarcts and bilateral frontal cortical leukomalacia
      following chronic maternal inhalation of carburetor cleaning fluid during
      pregnancy.
AB  - Little is known about the effect of inhalation of methanol and other solvents on
      the pregnancy and the growth of the fetus. We report a preterm male infant who
      developed cerebral infarcts in utero, leading to large areas of bilateral frontal
      cortical leukomalacia following chronic maternal inhalation of carburetor
      cleaning fluid during pregnancy. The infant presented with acute fetal distress
      with significant metabolic acidosis at birth. Initial hypotonia was followed by
      generalized hypertonicity. This infant did not exhibit typical facial features of
      fetal alcohol syndrome.

PMID- 14647173
TI  - Socioeconomic gradient in body size and obesity among women: the role of dietary
      restraint, disinhibition and hunger in the Whitehall II study.
AB  - OBJECTIVE: To examine the associations between three psychological eating
      behaviour variables--restraint, hunger and disinhibition--and body weight and
      size, and to assess their explanatory power for the employment grade gradients in
      body measurement. DESIGN: Cross-sectional analysis of self-report and clinical
      data. SUBJECTS: : In all, 1470 women (aged 45-68 y, mean 56.3, s.d. 6.0 y), body
      mass index (BMI) 26.3 (4.8) kg/m(2) at phase 5 (1997-98) of the Whitehall II
      study. MEASUREMENTS: Employment grade was measured in six bands ranging from
      clerical (lowest) to administrative (highest). Five measures of body size were
      examined: BMI, weight in kilograms, waist and hip measurement in centimetres and
      waist-hip ratio. The eating behaviour variables were measured using Stunkard and
      Messick's (1985) Three-Factor Eating Questionnaire (TFEQ). RESULTS: Disinhibition
      and hunger scores were strongly and directly associated with all measures of body
      weight and size. Restraint score was not directly associated with body size and
      weight. An interaction between restraint and disinhibition scores was found. The
      low-restraint-high-disinhibition group (based on median score splits) were the
      heaviest (BMI 28.5 kg/m(2)) and largest (waist 85.8 cm), while the low-restraint
      low-disinhibition group were the lightest (BMI 24.2 kg/m(2)) and smallest (waist
      76.3 cm). Employment grade gradients in body weight and size remained largely
      unchanged after adjustment for dietary restraint. Moderate attenuations were
      found for disinhibition scores (3.6-15.0%) and hunger (4.8-19.9%) on the five
      body-size measures. CONCLUSION: Among middle-aged women high scores on hunger and
      disinhibition, as measured by the TFEQ, are associated with greater body size.
      Restraint relates to body size through its interaction with disinhibition.
      Individuals with high disinhibition and any level of restraint are heavier and
      larger than those with low levels of disinhibition. High disinhibition coupled
      with low levels of restraint is associated with the greatest weight and size.
      Hunger and disinhibition explain a moderate amount of the gradient in body size
      across employment grade and may be useful concepts for future work on the socio
      economic gradient in obesity and overweight.

PMID- 14647174
TI  - Effect of organ and tissue masses on resting energy expenditure in underweight,
      normal weight and obese adults.
AB  - BACKGROUND: In normal-weight subjects, resting energy expenditure (REE) can be
      accurately calculated from organ and tissue masses applying constant organ
      specific metabolic rates. This approach allows a precise correction for between
      subjects variation in REE, explained by body composition. Since a decrease in
      organ metabolic rate with increasing organ mass has been deduced from
      interspecies comparison including human studies, the validity of the organ- and
      tissue-specific REE calculation remains to be proved over a wider range of fat
      free mass (FFM). DESIGN: In a cross-sectional study on 57 healthy adults (35
      females and 22 males, 19-43 y; 14 underweight, 25 intermediate weight and 18
      obese), magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry
      (DXA) were used to assess the masses of brain, internal organs, skeletal muscle
      (MM), bone and adipose tissue. REE was measured by indirect calorimetry (REEm)
      and calculated from detailed organ size determination by MRI and DXA (REEc1), or
      in a simplified approach exclusively from DXA (REEc2). RESULTS: We found a high
      agreement between REEm and REEc1 over the whole range of FFM (28-86 kg). REE
      prediction errors were -17 +/- 505, -145 +/- 514 and -141 +/- 1058 kJ/day in
      intermediate weight, underweight and obese subjects, respectively (n.s.).
      Regressing REEm on FFM resulted in a significant positive intercept of 1.6 MJ/day
      that could be reduced to 0.5 MJ/day by adjusting FFM for the proportion of
      MM/organ mass. In a multiple regression analysis, MM and liver mass explained 81%
      of the variance in REEm. DXA-derived REE prediction showed a good agreement with
      measured values (mean values for REEm and REEc2 were 5.72 +/- 1.87 and 5.82 +/-
      1.51 MJ/day; difference n.s.). CONCLUSION: Detailed analysis of metabolically
      active components of FFM allows REE prediction over a wide range of FFM. The data
      provide indirect evidence for a view that, for practical purposes within humans,
      the specific metabolic rate is constant with increasing organ mass. Nonlinearity
      of REE on FFM was partly explained by FFM composition. A simplified REE
      prediction algorithm from regional DXA measurements has to be validated in future
      studies.

PMID- 14647175
TI  - Behavioural correlates of successful weight reduction over 3 y. Results from the
      Lean Habits Study.
AB  - OBJECTIVE: To examine behavioural characteristics of subjects with successful
      long-term weight reduction. DESIGN: Prospective cohort study with 3 y follow-up.
      SETTING: Multicentre study of participants of a commercial weight-reduction
      programme (BCM-Programme). SUBJECTS: Until February 2000, 6857 voluntary study
      participants were included. Analyses are based on 1247 subjects with complete 3 y
      data. INTERVENTIONS: Open-group dietary and behavioural counselling with initial
      meal substitutions. RESULTS: Subjects show a number of significant behavioural
      improvements, for example, choice of low-fat food, flexible control of eating
      behaviour and coping with stress. Subjects who maintain these changes by the end
      of the first year have a higher probability of successful weight reduction after
      3 y. CONCLUSIONS: Successful weight maintenance is associated with more
      pronounced improvements of health behaviours after 1 y. The likelihood of success
      increases with the number of behavioural patterns which are involved in the
      process of change.

PMID- 14647176
TI  - Weight cycling and cardiovascular risk factors in obesity.
AB  - OBJECTIVE: To assess the relationship between weight cycling and some
      cardiovascular risk factors in a wide sample of obese subjects. DESIGN: Cross
      sectional study with retrospective evaluation of weight and dieting history.
      SUBJECTS: In all, 459 obese subjects, 340 women and 119 men (age: 19-65 y; BMI:
      30-69 kg/m2). MEASUREMENTS: Body composition and fat distribution (by
      bioelectrical impedance analysis and anthropometry), systolic and diastolic blood
      pressure, plasma glucose, total and HDL cholesterol, triglycerides, insulin and
      insulin resistance by HOMAir, various weight cycling indices. RESULTS: A positive
      correlation between weight cycling indices, BMI and percent body fat was found in
      both genders. Also, the maximum absolute amount of weight regained following a
      single diet episode was significantly associated to insulin and HOMAir in both
      genders. However, these correlations disappeared when the data were controlled
      for age and BMI. CONCLUSION: In obese subjects of both genders weight cycling,
      and in particular weight regain, does not appear to be associated with adverse
      effects on body composition, fat distribution or cardiovascular risk factors in
      an independent manner, but rather in relation to fat accumulation over years.

PMID- 14647177
TI  - Food purchased away from home as a predictor of change in BMI z-score among
      girls.
AB  - OBJECTIVES: To assess the relationship between eating food purchased away from
      home (FAH) and longitudinal change in body mass index (BMI) z-score among girls,
      and to assess the longitudinal tracking of eating FAH from childhood through
      adolescence. DESIGN: Participants kept 7-day dietary records at two points in
      time. The records included the place and time for all foods consumed. We recorded
      how often participants ate FAH, calculated the percent of total energy derived
      from FAH, and classified foods as quick-service food, coffee-shop food, or
      restaurant food. PARTICIPANTS: Healthy girls (n=101) between the ages of 8 and 12
      y at baseline and 11 and 19 y at follow-up participated in a longitudinal study
      of growth and development at the Massachusetts Institute of Technology.
      STATISTICAL ANALYSES: Analysis of variance was used to assess the relationship
      between change in BMI z-score and both the frequency of eating FAH and energy
      derived from eating FAH. The participants' baseline BMI z-score was a significant
      covariate and was controlled for in both models. We used the kappa coefficient to
      assess FAH tracking from childhood through adolescence. RESULTS: The frequency of
      eating quick-service food at baseline was positively associated with change in
      BMI z-score (F=6.49, P<0.01). Participants who ate quick-service food twice a
      week or more at baseline had the greatest mean increase in BMI z-score compared
      to those who ate quick-service food once a week or not at all. Quick-service food
      eating tracked slightly from childhood through adolescence (k=0.17, P<0.05).
      DISCUSSION: Adolescent girls who eat quick-service food twice a week or more are
      likely to increase their relative BMI over time.

PMID- 14647178
TI  - Subcutaneous adipose tissue blood flow varies between superior and inferior
      levels of the anterior abdominal wall.
AB  - OBJECTIVE: Blood flow regulation is thought to mediate the metabolic functions of
      adipose tissue. Different depots, and even different layers within the
      subcutaneous adipose tissue, may vary in metabolic activity and blood flow.
      Therefore, we investigated if any differences in subcutaneous adipose tissue
      blood flow (ATBF) exist at different locations of the anterior abdominal wall.
      METHODS: ATBF was measured 8-10 cm above or below the umbilicus, at 8-10 cm (both
      sides) from the midline, in 18 healthy subjects (BMI range 18-33 kg/m(2)).
      Measurements of ATBF were performed using (133)xenon washout, during a stable
      baseline period and after ingestion of 75 g of glucose. RESULTS: At baseline,
      ATBF was greater at the upper level compared to the lower level (4.4+/-0.3 vs
      3.8+/-0.2 ml min(-1) 100 g tissue(-1), P=0.005), but was not different between
      the right and the left sides at either level. ATBF increased in response to oral
      glucose at all sites. The mean increase at the superior level was also greater
      than the inferior level (3.5+/-0.7 vs 2.2+/-0.6 ml min(-1) 100 g tissue(-1),
      P=0.001). CONCLUSIONS: Even at a constant depth and with only 16-20 cm difference
      between sites, there are significant differences in function of the same adipose
      depot. These findings have physiological and methodological implications for in
      vivo metabolic studies of human adipose tissue.

PMID- 14647179
TI  - Relationship between temperament, nonresting energy expenditure, body
      composition, and physical activity in girls.
AB  - OBJECTIVES: To assess the extent that predilection for movement, as measured by a
      temperament questionnaire (activity temperament), contributes to nonresting
      energy expenditure and body composition in girls. DESIGN, SETTING, AND
      PARTICIPANTS: Baseline data for 196 premenarcheal non-obese girls aged 8-12 y
      were obtained from a longitudinal study of growth and development. The
      association of activity temperament with nonresting energy expenditure in girls
      with low and high levels of physical activity was evaluated, as was the
      association of activity temperament with body composition. MEASURES: Maternal
      reports of child activity temperament were obtained by questionnaire. Nonresting
      energy expenditure was calculated as total energy expenditure (measured by doubly
      labeled water) minus resting energy expenditure (obtained by indirect
      calorimetry). Body composition was estimated by total body water. Questionnaires
      and activity diaries were used to assess physical activity and sedentary
      behavior. RESULTS: Higher activity temperament was associated with higher
      nonresting energy expenditure after multivariate control for weight, vigorous
      activity, walking and light activity, and television viewing, although activity
      temperament did not account for a large percentage of the variability in
      nonresting energy expenditure (partial squared correlation coefficient=0.03). In
      girls with physical activity levels below the median, high activity temperament
      was associated with a mean+/-s.d., nonresting energy expenditure of 310+/-138 kJ
      (74+/-33 kcal) above that of girls with a low activity temperament. Girls with a
      high activity temperament had less body fat than did girls with a low activity
      temperament (21.6 vs 24.5%, a difference of 2.9 percentage points; 95% confidence
      interval, 1.3-4.4 percentage points). CONCLUSION: Predilection for movement, as
      measured by a temperament questionnaire, contributes to nonresting energy
      expenditure and may be useful in capturing an aspect of energy expenditure in
      population studies. The cross-sectional observation that girls with a high
      activity temperament were leaner than girls with a low activity temperament
      suggests that a constitutional predilection for movement may play a role in the
      development of obesity.

PMID- 14647180
TI  - Sex differences in the relationships of abdominal fat to cardiovascular disease
      risk among normal-weight white subjects.
AB  - The objectives of this study are to investigate the relationships between
      abdominal fat and risk factors for cardiovascular disease (CVD) among normal
      weight (NW) white subjects and to determine how these relationships differ by
      sex. NW adults (177 males and 258 females) and overweight adults (133 males and
      111 females) from the Quebec Family Study and the HERITAGE Family Study were
      retained for this study. Risk factors included systolic and diastolic blood
      pressures, low-density lipoprotein and high-density lipoprotein cholesterols,
      triglycerides, and fasting glucose. Only in NW female adults, abdominal visceral
      fat (AVF) area assessed by computed tomography was significantly correlated with
      all risk factors, except for fasting glucose, even after age, study cohort, and
      fat mass were taken into account. NW female subjects with at least one risk
      factor had a significantly higher AVF than those without risk factors, although
      the difference was small. Thus, only NW female adults with more AVF tended to
      have a more adverse CVD risk factor profile.

PMID- 14647181
TI  - Longitudinal study of the long-term relation between physical activity and
      obesity in adults.
AB  - BACKGROUND: Earlier observational studies of the relation between physical
      activity and obesity are inconsistent and ambiguous, showing a clear cross
      sectional inverse relation, and a prospective association only when physical
      activity at the time of follow-up is included. OBJECTIVE: To examine the long
      term effect of leisure time physical activity (LTPA) on subsequent development of
      obesity and the effect of body weight on later physical inactivity in a
      population-based longitudinal setting taking into account the effects of
      historical changes on future changes as well as pertinent confounders. DESIGN:
      The study included 3653 women and 2626 men aged 20-78 y selected at random within
      sex-age strata from the general population of Copenhagen. At two surveys, 5 y
      apart, LTPA, body mass index (BMI) (weight/height2, kg/m2), several possible
      confounders and modifying factors were assessed. Obesity (defined as BMI > or =30
      kg/m2) and LTPA was assessed at the 3rd survey 10 y later. Odds ratios (with 95%
      confidence limits) for developing obesity between the last two surveys were
      estimated by logistic regression analysis, taking into account baseline and
      preceding changes in BMI and LTPA. A similar analysis of odds ratios for physical
      inactivity as outcome at the 3rd survey was conducted. RESULTS: Compared to
      physical inactivity, the odds ratios of development of obesity among women with
      medium and high level of activity were 0.81 (0.53, 1.25) and 1.16 (0.73, 1.84),
      respectively, and among men, the odds ratios were 1.28 (0.71, 2.33) and 1.65
      (0.91, 2.99), respectively. Compared to median BMI, the odds ratio of later
      physical inactivity among women with high BMI was 1.91 (1.39, 2.61), and among
      men the odds ratio was 1.50 (1.01, 2.22). The associations were not confounded or
      modified by age, pre-existing diseases, smoking, alcohol intake, educational
      level, occupational physical activity or by familial predisposition to obesity.
      CONCLUSION: This study did not support that physical inactivity as reported in
      the freely living adult population in the long term is associated with the
      development of obesity, but the study indicates that obesity may lead to physical
      inactivity.

PMID- 14647182
TI  - Short-term predictors of overweight in early adolescence.
AB  - OBJECTIVE: To identify short-term predictors of risk for overweight in early
      adolescence in a sample of Caucasian origin subjects, in Cyprus. SUBJECTS: A
      total of 357 subjects (178 males) with baseline age 11.5+/-0.4 y were re
      evaluated after a mean of 1.6+/-0.5 y. MEASUREMENTS: Body weight and height,
      calculated body mass index (BMI), and blood pressure at baseline and follow-up.
      Serum lipids were determined at baseline. Obesity and overweight were defined at
      baseline and follow-up, according to the International Obesity Task Force data
      set. Socioeconomic class was determined. Self-reported parental weight and height
      were used to calculate the parental BMI. BMI tracking and changes in BMI
      categories were calculated (with 95% confidence interval (CI)). The future risk
      of overweight in baseline normal weight subjects was predicted using logistic
      regression analyses, where only normal weight subjects at baseline were included.
      RESULTS: More males remained in the overweight or obese category than females:
      86.7% (95% CI: 73.2, 94.9) vs 71.8% (95% CI: 55.1, 85.0), respectively, P=0.03.
      The identified predictors for future overweight were paternal obesity, odds ratio
      (OR): 7.1 (95% CI: 1.3, 38.0), systolic blood pressure >95th percentile, OR: 8.9
      (95% CI: 1.9, 41.7), high triglyceride levels, OR: 4.2 (95% CI: 1.0, 16.9) and
      low HDL-cholesterol levels, OR: 7.6 (95% CI: 1.7, 34.3). CONCLUSIONS:
      Triglycerides and HDL-cholesterol levels have been proved predictors for
      overweight in early adolescence for the first time. The different sex pattern in
      BMI tracking observed, and also the different environmental influences on future
      overweight risk compared to other studies, indicate that local circumstances
      should be considered when implementing national intervention strategies for the
      prevention of obesity.

PMID- 14647183
TI  - Promoting long-term weight control: does dieting consistency matter?
AB  - OBJECTIVE: The present study examined whether long-term weight loss maintenance
      is enhanced by maintaining the same diet regimen across the week and year or by
      dieting more strictly on weekdays and nonholiday periods than at other times.
      METHOD: National Weight Control Registry participants (N=1429) indicated on an
      eight-point scale whether they dieted more strictly on weekends than weekdays,
      adhered to the same diet regimen throughout the week, or dieted more strictly on
      weekdays. Participants responded to a similar question about holiday and vacation
      eating. Participants were then followed prospectively to determine whether scores
      on these questions were related to self-reported weight regain over the
      subsequent 12 months. RESULTS: There was a linear relationship between scores on
      the dieting consistency questions and weight change over the 1-y period (P's
      <0.01), with smaller weight gains in those who reported more consistency.
      Participants who reported a consistent diet across the week were 1.5 times more
      likely to maintain their weight within 5 pounds over the subsequent year
      (OR=1.58, 95% CI: 1.2-2.2) than participants who dieted more strictly on
      weekdays. A similar relationship emerged between dieting consistency across the
      year and subsequent weight regain. CONCLUSION: Dieting consistency appears to be
      a behavioral strategy that predicts subsequent long-term weight loss maintenance.

PMID- 14647184
TI  - Increasing trends of obesity in Sweden between 1996/97 and 2000/01.
AB  - BACKGROUND: During the last two decades, obesity has reached epidemic proportions
      in industrialised societies such as Sweden. OBJECTIVE: The first aim of this
      study is to examine whether the body mass index (BMI) and obesity increased
      between 1996/97 and 2000/01 in different subgroups in the Swedish population. The
      second aim is to examine whether there were any differences in BMI between
      subgroups of the population, characterised by age, gender, educational status,
      smoking habits, degree of urbanisation, and country of birth. The third aim is to
      examine whether BMI increased between the two periods after adjustment for all
      the explanatory variables. METHODS: This study is based on two cross-sectional,
      random samples of the entire population aged 16-84 y, the first from 1996/97
      including 5622 men and 5940 women and the second from 2000/01 including 5515 men
      and 5838 women. To investigate the possible change in obesity between the two
      periods, a logistic model adjusted for age was applied, after stratification by
      gender. To study the relationship between BMI and the explanatory variables, and
      the possible change in the subgroups of the population between the two periods, a
      linear regression model was used. RESULTS: The total BMI mean increased by 0.4
      units from 1996/97 to 2000/01 for both men and women. The prevalence of obesity
      also increased to about 10% in 2000/01. In some subgroups, the prevalence of
      obesity was especially high, for example, men and women aged 55-74 y, men with
      middle educational status, women with low educational status, former smokers, and
      Finnish-born men and women. CONCLUSIONS: These findings illustrate that both BMI
      and obesity increased in the Swedish population between 1996/97 and 2000/01. This
      increase in BMI and obesity is most likely due to environmental factors, such as
      diet and a sedentary lifestyle. Health interventions need to target both certain
      subgroups and the whole population.

PMID- 14647193
TI  - FcgammaRIIB gene polymorphisms in Japanese periodontitis patients.
AB  - Human type II low-affinity receptor for immunoglobulin G (FcgammaRII) constitutes
      a clustered gene family consisting of FcgammaRIIA, IIB and IIC genes. FcgammaRIIB
      is unique in its ability to transmit inhibitory signals in B cells via
      immunoreceptor tyrosine-based inhibitory motif (ITIM). B-cell activation and
      subsequent elevated production of IgG are the immunopathological features of
      inflammatory disease such as periodontitis. To determine whether an association
      with periodontitis susceptibility exists, genetic polymorphisms of FcgammaRIIB
      were examined in Japanese patients with aggressive periodontitis (AGP) and
      chronic periodontitis (CP), and in the race-matched healthy controls (HCs). A
      significant difference was observed in the distribution of FcgammaRIIB-232I/T
      allele (exon 5) between the AGP and HC groups, with enrichment of the 232T in the
      AGP group (P=0.006). In addition, the FcgammaRIIB-nt 646-184A/G allele (intron 4)
      distribution was significantly different between the CP and HC groups, with
      enrichment of the nt 646-184A in the CP group (P=0.011). These results document
      the association of FcgammaRIIB gene polymorphisms with susceptibility to
      periodontitis in the Japanese.

PMID- 14647192
TI  - Genomic polymorphic profiles in an Irish population with meningococcaemia: is it
      possible to predict severity and outcome of disease?
AB  - Patients with meningococcal disease have increased plasma levels of
      proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha, with higher levels
      associated with fatal outcome. This study investigated whether polymorphisms in
      genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and
      IL-1Ra, are associated with the outcome in patients with meningococcal disease.
      Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389
      controls. The IL-6 -174 G/G and IL-10 -1082 A/A genotypes were more frequent in
      nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients
      with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL
      10). An association was also found between meningococcal disease and the IL-1RN
      VNTR polymorphism, but no association was observed with the LTA +252, TNF -308,
      IL-10 -592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in
      the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in
      meningococcal disease.

PMID- 14647194
TI  - Novel polymorphisms and the definition of promoter 'alleles' of the tumor
      necrosis factor and lymphotoxin alpha loci: inclusion in HLA haplotypes.
AB  - Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) influence a variety of
      cellular responses and play a complex role in the immune response. Several single
      nucleotide polymorphisms (SNPs) have been reported in these major
      histocompatibility complex (MHC)-linked loci; however, a comprehensive
      examination of polymorphisms in the promoter regions of TNF and LTA has not been
      carried out and was undertaken here. Seven novel SNPs in LTA were identified by
      sequence analysis of 69 samples. Eight novel TNF alleles and 16 novel LTA alleles
      were designated. The TNF alleles clustered into two closely related groups, while
      the LTA alleles clustered into three distinct groups using phylogenetic and
      percentage difference analyses. A total of 52 unique TNF-LTA-HLA haplotypes are
      reported. There appear to be some associations between TNF/LTA alleles and HLA
      haplotypes, but not with specific HLA alleles. The majority of the SNPs appear to
      be randomly associated within and between the two loci except for the LTA SNPs at
      -293, +81 and +369. These observations may provide an explanation for the
      oftentimes contradictory results of studies associating individual cytokine gene
      SNPs with expression level phenotypes, HLA and disease.

PMID- 14647195
TI  - Genome-wide TDT analysis in a localized population with a high prevalence of
      multiple sclerosis indicates the importance of a region on chromosome 14q.
AB  - Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a
      strong genetic component, but apart from the HLA gene complex, additional genetic
      factors have proven difficult to map in the general population. Thus, localized
      populations, where MS patients are assumed to be more closely related, may offer
      a better opportunity to identify shared chromosomal regions. We have performed a
      genome-wide scan with 834 microsatellite markers in a data set consisting of 54
      MS patients and 114 healthy family members. A group of families from a small
      village were possible to track back to common ancestors living in the 17th
      century. We used single marker- and haplotype-based transmission disequilibrium
      test (TDT) analysis and nonparametric linkage analysis to analyze genotyping
      data. Regions on chromosomes 2q23-31, 6p24-21, 6q25-27, 14q24-32, 16p13-12 and
      17q12-24 were found to be in transmission disequilibrium with MS. Strong
      transmission disequilibrium was detected in 14q24-32, where several dimarker
      haplotypes were in transmission disequilibrium in affected individuals. Several
      regions showed modest evidence for linkage, but linkage and TDT were both clearly
      positive only for 17q12-24. All patients and controls were also typed for HLA
      class II genes; however, no evidence for a gene-gene interaction was observed.

PMID- 14647196
TI  - Cloning and characterization of GITR ligand.
AB  - The gene encoding the natural ligand of murine glucocorticoid-induced tumor
      necrosis factor receptor (GITR) was cloned and characterized. The putative GITR
      ligand (GITRL) is composed of 173 amino acids with features resembling those of
      type II membrane proteins and is 51% identical to the human activation-inducible
      TNF receptor (AITR) ligand, TL6. Expression of the GITRL is restricted to
      immature and mature splenic dendritic cells. GITRL binds GITR expressed on HEK
      293 cells and triggers NF-kappaB activation. Functional studies reveal that
      soluble CD8-GITRL prevents CD4+CD25+ regulatory T-cell-mediated suppressive
      activities.

PMID- 14647197
TI  - A 24-bp duplication in exon 10 of human chitotriosidase gene from the sub-Saharan
      to the Mediterranean area: role of parasitic diseases and environmental
      conditions.
AB  - Human chitotriosidase (Chit) is a member of the chitinase family and it is
      synthesized by activated macrophages. Recently, a genetic polymorphism was found
      to be responsible for the common deficiency in Chit activity, frequently
      encountered in different populations. We analyzed the Chit gene in some ethnic
      groups from the Mediterranean and African areas, to evaluate whether the Chit
      gene polymorphism correlates with the changes in environmental features and the
      disappearance of parasitic diseases. We found a heterozygote frequency for the
      duplication of 24 bp in exon 10 of 44% in Sicily and 32.71% in Sardinia, whereas
      those homozygous Chit deficient were 5.45 and 3.73%, respectively. In contrast,
      in Benin and Burkina Faso, both mesoendemic regions for Plasmodium falciparum
      malaria and other infections due to intestinal parasites, a low incidence of Chit
      mutation was found (heterozygous 0 and 2%, respectively) and no subject was
      homozygous for Chit deficiency. Our results provide evidence of the fact that the
      low frequency or the absence of mutant Chit gene may represent a protective
      factor in the population still living in disadvantaged environmental conditions.
      The present study suggests that the disappearance of parasitic diseases and the
      improved environmental conditions may have ensued the occurrence of a high
      percentage of 24-bp mutation in Sicily, in Sardinia and in other Mediterranean
      countries, whereas in the sub-Saharan regions (Benin and Burkina Faso), the
      widespread parasitic diseases and the poor social status have contributed to
      maintenance of the wild-type Chit gene.

PMID- 14647198
TI  - Genetic interactions between susceptibility loci reveal epistatic pathogenic
      networks in murine lupus.
AB  - Interactions between Sle1 and other susceptibility loci were required for disease
      development in the NZM2410 model of lupus. Sle1 corresponds to at least three
      subloci, Sle1a, Sle1b, and Sle1c, each of which independently causes loss of
      tolerance to chromatin, but displays a distinctive immune profile. We have used
      congenic strains to analyze the interactions between the Sle1 subloci and other
      lupus susceptibility loci using Y autoimmunity accelerator (Yaa) and Faslpr as
      sensitizing mutations. Sle1 coexpressed with either one of these single
      susceptibility alleles resulted in a highly penetrant nephritis, splenomegaly,
      production of nephrophilic antibodies, and increased expression of B- and T-cell
      activation markers. Here, we show that only Sle1b interacted with Yaa to produce
      these phenotypes, suggesting that Sle1b and Yaa belong to the same functional
      pathway. Interactions between the three Sle1 loci and lpr resulted in lymphocyte
      activation and lupus nephritis, but a significant mortality was observed only for
      the Sle1a.lpr combination. This suggests a major role for the FAS pathway in
      keeping in check the loss of tolerance mediated by the Sle1 loci, especially for
      Sle1a. Our results illustrate the complexity of interactions between
      susceptibility loci in polygenic diseases such as lupus and may explain the
      clinical heterogeneity of the disease.

PMID- 14647200
TI  - Goal-oriented research.

PMID- 14647199
TI  - Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in
      autoimmune thyroid disease.
AB  - The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene on 2q33 is
      associated with autoimmune thyroid diseases (AITDs). Our earlier study in 56
      families showed linkage of 2q33 to the presence of thyroid antibodies (TAbs). The
      goals of this study were to confirm the linkage of the 2q33 region to TAbs, to
      fine map this region, and study the ICOS gene. We performed a linkage study in an
      expanded data set of 99 multiplex AITD-TAb families (529 individuals). The
      highest two-point LOD score of 2.9 was obtained for marker D2S325 on 2q33. To
      fine map this locus, we genotyped 238 Caucasian AITD patients and 137 controls
      for five additional markers in the linked locus, which contained the CTLA-4,
      CD28, and ICOS genes. The A/G single-nucleotide polymorphism at position 49 of
      CTLA-4 was associated with AITD (P=0.01, OR=1.5), while markers inside CD28 and
      ICOS were not. Functional studies have shown that the G allele was associated
      with reduced inhibition of T-cell proliferation by CTLA-4. We concluded that: (1)
      the AITD gene in the 2q33 locus is the CTLA-4 gene and not the CD28 or ICOS
      genes; and (2) the G allele is associated with decreased function of CTLA-4.

PMID- 14647201
TI  - What the public thinks it knows about science.

PMID- 14647202
TI  - Research politics, bottom up.

PMID- 14647203
TI  - Time for an overhaul?

PMID- 14647204
TI  - A second chance for hormone replacement therapy?

PMID- 14647206
TI  - Fibulins: physiological and disease perspectives.
AB  - The fibulins are a family of proteins that are associated with basement membranes
      and elastic extracellular matrix fibres. This review summarizes findings from
      studies of animal models of fibulin deficiency, human fibulin gene mutations,
      human tumours and injury models that have advanced our understanding of the
      normal and pathological roles of members of this formerly obscure family.

PMID- 14647207
TI  - LIM-domain-binding protein 1: a multifunctional cofactor that interacts with
      diverse proteins.
AB  - The ubiquitous nuclear adaptor protein LIM-domain-binding protein 1 (Ldb1) was
      originally identified as a cofactor for LIM-homeodomain and LIM-only (LMO)
      proteins that have fundamental roles in development. In parallel, Ldb1 has been
      shown to have essential functions in diverse biological processes in different
      organisms. The recent targeting of this gene in mice has revealed roles for Ldb1
      in neural patterning and development that have been conserved throughout
      evolution. Furthermore, the elucidation of the three-dimensional structures of
      LIM-Ldb1 complexes has provided insight into the molecular basis for the ability
      of Ldb1 to contact diverse LIM-domain proteins. It has become evident that Ldb1
      is a multi-adaptor protein that mediates interactions between different classes
      of transcription factors and their co-regulators and that the nature of these
      complexes determines cell fate and differentiation.

PMID- 14647208
TI  - Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other
      end of the spectrum.
AB  - Autosomal recessive limb-girdle muscular dystrophy linked to 19q13.3 (LGMD2I) was
      recently related to mutations in the fukutin-related protein gene (FKRP) gene.
      Pathogenic changes in the same gene were detected in congenital muscular
      dystrophy patients (MDC1C), a severe disorder. We have screened 86 LGMD
      genealogies to assess the frequency and distribution of mutations in the FKRP
      gene in Brazilian LGMD patients. We found 13 Brazilian genealogies, including 20
      individuals with mutations in the FKRP gene, and identified nine novel pathogenic
      changes. The commonest C826A European mutation was found in 30% (9/26) of the
      mutated LGMD2I alleles. One affected patient homozygous for the FKRP (C826A)
      mutation also carries a missense R125H change in one allele of the caveolin-3
      gene (responsible for LGMD1C muscular dystrophy). Two of her normal sibs were
      found to be double heterozygotes. In two unrelated LGMD2I families, homozygous
      for novel missense mutations, we identified four asymptomatic carriers, all older
      than 20 years. Genotype-phenotype correlation studies in the present study as
      well as in patients from different populations suggests that the spectrum of
      variability associated with mutations in the FKRP gene seems to be wider than in
      other forms of LGMD. It also reinforces the observations that pathogenic
      mutations are not always determinant of an abnormal phenotype, suggesting the
      possibility of other mechanisms modulating the severity of the phenotype that
      opens new avenues for therapeutic approaches.

PMID- 14647209
TI  - Alternatively spliced, truncated human BRCA2 isoforms contain a novel coding
      exon.
AB  - The protein truncation test (PTT) employs in vitro transcription and translation
      of amplified cDNA and exonic gDNA to reveal truncating germ-line mutations. In a
      series of PTT analyses, abnormal splicing in the region encompassing exons 20-23
      of BRCA2 was discovered in leucocytes from high-risk breast cancer patients.
      Although sequencing of the genomic DNA in this region failed to reveal a
      detectable mutation in these patients, cDNA obtained from this region of BRCA2
      uncovered numerous alternative splice isoforms. PTT analysis and nested RT-PCR
      using RNA from leucocytes from healthy individuals, normal tissue and breast and
      ovarian cancer tumours demonstrated the presence of these alternatively spliced
      transcripts in all cases. The splice forms appeared to be more prominent in RNA
      from aged blood, suggesting that isoform expression was conditional. It is
      therefore important to distinguish naturally occurring alternative splicing from
      true splice defects due to mutations when interpreting PTT results.

PMID- 14647210
TI  - A high frequency of BRCA2 gene mutations in Polish families with ovarian and
      stomach cancer.
AB  - Germ-line mutations in the BRCA2 gene are associated with a wide range of cancer
      types, including the breast, ovary, pancreas, prostate and melanoma. In this
      study, we evaluated the importance of a family history of stomach cancer in
      predicting the presence of a BRCA2 mutation in Polish patients with ovarian
      cancer. A BRCA2 mutation was found in eight of 34 women with ovarian cancer and a
      family history of stomach cancer versus three of 75 women with ovarian cancer and
      a family history of ovarian cancer, but not of stomach cancer (odds ratio=7.4;
      95% CI 1.8-30; P=0.004). The results of this study suggest that, in the Polish
      population, the constellation of ovarian and stomach cancer predicts the presence
      of a germ-line BRCA2 mutation and confirms that stomach cancer is part of the
      spectrum of BRCA2 mutations. It is expected that the penetrance of BRCA2
      mutations for stomach cancer will vary from country to country, reflecting local
      environmental and lifestyle factors.

PMID- 14647214
TI  - Hydrothermal treatment and malting of barley improved zinc absorption but not
      calcium absorption in humans.
AB  - OBJECTIVE: To study whether hydrothermal treatment or malting of barley (cv.
      Blenheim) improves zinc and calcium absorption in humans. DESIGN: : Two groups of
      10 and 12 healthy subjects, respectively, were in a period of 2 months in a
      fasting state, served two single meals each containing porridge or breakfast
      cereals prepared from processed or unprocessed (control) barley (60 g). The meals
      included 200 g of milk, extrinsically labelled with (65)Zn and (47)Ca. Whole-body
      retention of both minerals was measured. SETTING: The study was carried out at
      the Department of Radiation Physics, Sahlgrenska University Hospital, Goteborg.
      SUBJECTS: The subjects were recruited among students at the Goteborg University.
      None dropped out. INTERVENTIONS: The activities of (65)Zn and (47)Ca were
      measured by whole-body counting four to five times over a 4-week period after
      each meal. RESULTS: Zinc absorption from hydrothermally treated barley porridge,
      containing 28 mg P as inositol tri- to hexaphosphates (InsP(3)-InsP(6)), was
      significantly higher (P<0.001) than from control porridge containing 111 mg P as
      InsP(3)-InsP(6), 25.2+/-6.9 vs 11.0+/-2.5% (n=12). Calcium absorption did not
      differ (P>0.05), 21.1+/-6.8 vs 19.5+/-4.7% (n=12). Zinc absorption from breakfast
      cereals of malted barley with phytase activity and containing 70 mg P as InsP(3)
      InsP(6,) was significantly higher (P<0.05) than from flakes of barley, containing
      108 mg P as InsP(3)- InsP(6) and no phytase activity, 22.9+/-5.8 vs 14.8+/-4.6%
      (n=10). The calcium absorption was 21.3+/-6.5 vs 18.5+/-4.3% (n=10) and did not
      differ significantly (P>0.05). CONCLUSION: Improvements of zinc absorption in
      breakfast meals can be achieved by optimised hydrothermal treatment or malting of
      barley. Calcium absorption was not influenced in the meals in this study.
      SPONSORSHIP: Supported by Semper AB, Sweden, Oy Lahden Polttimo, Finland, the SL
      Foundation, Sweden, Swedish National Board for Industrial and Technical
      Development (NUTEK), the Nordic Industrial Foundation, Swedish Council for
      Forestry and Agricultural Research (SJFR, project no 50.0306/97).

PMID- 14647215
TI  - Dietary and nutritional patterns in an elderly rural population in Northern and
      Southern Italy: (I). A cluster analysis of food consumption.
AB  - OBJECTIVE: To describe the food consumption patterns of Italian elderly subjects
      and the factors associated with different dietary habits. DESIGN: Cross-sectional
      study. SETTING: Population-based study. SUBJECTS: A total of 847 men and 1465
      women aged 65 y or older, living in rural areas in the province of Pavia
      (Northern Italy) and near Cosenza (Southern Italy) in 1992-1993. INTERVENTIONS:
      The dietary information was collected by means of a quantitative food-frequency
      questionnaire, with cluster analysis being used to segregate the subjects on the
      basis of similarities in their food consumption. A generalised logistic
      regression model including residence, age, living status, education, physical
      activity and degree of disability was fitted to assess the factors associated
      with different food consumption habits. RESULTS: Six dietary clusters were
      selected for men and seven for women. The largest cluster for both genders was
      "small eaters" (46% of men and 51% of women); "big eaters", "light diet" and
      "alcohol" clusters were also identified for both genders. The men were also
      grouped into "balanced diet" and "cheese" clusters, and the women into "sweet",
      "greens" and "butter" clusters. CONCLUSIONS: In addition to the influence of the
      area of residence--residents in Northern Italy consume greater amounts of animal
      fats, sugar and alcoholic beverages, and those living in Southern Italy have a
      greater intake of fruit, vegetables, fish and olive oil--all of the other studied
      variables predicted the probabilities of falling into a specific dietary cluster.
      SPONSORSHIP: National Research Council (Italy)--Invecchiamento Project No.
      95.01048. PF40.

PMID- 14647216
TI  - Dietary and nutritional patterns in an elderly rural population in Northern and
      Southern Italy: (II). Nutritional profiles associated with food behaviours.
AB  - OBJECTIVE: To describe the nutritional profiles of the food consumption patterns
      identified in an elderly Italian rural population. DESIGN: Cross-sectional study.
      SETTING: : Population-based study. SUBJECTS: A total of 847 men and 1465 women
      aged 65 y or older, resident in rural areas in the province of Pavia (Northern
      Italy) and near Cosenza (Southern Italy) in 1992-1993. INTERVENTIONS: A cluster
      analysis segregated the subjects into six groups for men and seven for women on
      the basis of similarities in their food intake (see companion paper). The mean
      daily energy, macronutrient, mineral and vitamin intakes were calculated for the
      sample as a whole and for each cluster, and then compared with the age- and
      gender-specific recommended daily allowances for the Italian population. RESULTS:
      The largest cluster ("small eaters", which included about half of the population)
      had an insufficient intake of essential fatty acids, calcium, potassium, zinc
      (men), iron (women), thiamin, riboflavin, niacin, beta-carotene, and vitamins A,
      D and E. The most noticeable characteristics of some of the other clusters were a
      high intake of fats, a high proportion of total energy provided by sugars, a high
      intake of vitamin C, folic acid and beta-carotene, and a high alcohol
      consumption. Furthermore, sodium intake was too high in all of the clusters and
      vitamin D intake was generally inadequate. CONCLUSIONS: The dietary habits of
      elderly Italians living in rural areas combine elements of the Mediterranean and
      "wealthy" diets. SPONSORSHIP: National Research Council (Italy) - Invecchiamento
      Project no. 95.01048.PF40.

PMID- 14647217
TI  - Variation in the application of methods used for predicting energy requirements
      in acutely ill adult patients: a survey of practice.
AB  - OBJECTIVE: To determine current methods used by dietitians for estimating the
      energy requirement of a chronically and acutely ill adult patient and the
      variation in the application of methods. DESIGN: A cross-sectional survey
      including a case study. SETTING: Acute care adult hospitals in Australia.
      SUBJECTS: A total of 307 dietitians (66.2% response rate). INTERVENTION: Surveys
      were posted to hospitals. A reminder letter was sent to all hospitals 2 weeks
      after the initial posting and a follow-up survey was sent 6 weeks after the
      initial posting to non-respondents. RESULTS: Respondents calculated a mean energy
      requirement for the case study of 9780+/-1410 kJ/day. One-third of respondents
      calculated energy requirement within +/-500 kJ of the mean. Respondents primarily
      used the Schofield equations (67.4%) followed by the Harris-Benedict equations
      (25.9%) to estimate energy requirement. Estimates using the Schofield equations
      calculated the highest mean energy requirement. The median injury factor used in
      the calculations was 1.3 (1.0-1.5). The values and reasons for the selection of
      injury factors varied widely. Calculated energy requirement did not differ with
      the aims of nutritional care-maintaining current weight (9700+/-1370 kJ/day) or
      increasing weight (9790+/-1380 kJ/day). CONCLUSION: There was considerable
      variation in the methods and factors used for estimating energy requirement,
      resulting in a wide range of calculated requirements. The application of
      prediction methods to individuals in acute care does not appear to be universally
      understood among dietitians. Dietitians require an understanding of the correct
      application, appropriate use, and limitations of these prediction methods.

PMID- 14647218
TI  - Effect of meal sequence on postprandial lipid, glucose and insulin responses in
      young men.
AB  - OBJECTIVE: To investigate whether the postprandial changes in plasma
      triacylglycerol (TAG), nonesterified fatty acids (NEFA), glucose and insulin
      concentrations in young men were the same if an identical meal was fed at
      breakfast and lunch, and if the response to lunch was modified by consumption of
      breakfast. METHODS: In two trials (1 and 2) healthy subjects (age 22+/-1 y, body
      mass index 22+/-2 kg/m(2)) were fed the same mixed macronutrient meal at
      breakfast at 08:00 h and lunch at 14:00 h. In the third trial, no breakfast was
      fed and the overnight fast extended until lunch at 14:00 h. Addition of [1,1,1
      (13)C]tripalmitin to one meal in each trial was used to distinguish between
      endogenous and meal-derived lipids. RESULTS: The postprandial changes in TAG,
      NEFA and glucose concentrations were similar in trials 1 and 2. The change in
      plasma total TAG concentration was about two fold less (P<0.05) after lunch
      compared to breakfast. Postprandial NEFA suppression was the same after breakfast
      and lunch. Glucose and insulin responses were significantly greater following
      lunch suggesting decreasing insulin sensitivity during the day. Consumption of
      breakfast did not alter the postprandial total TAG or NEFA responses after lunch.
      Measurement of [(13)C]palmitic acid concentration showed that handling of TAG and
      NEFA from the meal was the same after breakfast and lunch, and was not altered by
      consumption of breakfast. CONCLUSIONS: Overall, these data suggest that in young,
      healthy men regulation of plasma TAG from endogenous sources, principally VLDL,
      but not chylomicrons during the postprandial period leads to differences in the
      magnitude of lipaemic response when the same meal was consumed at breakfast or at
      lunch 6 h later.

PMID- 14647219
TI  - Tomato consumption and plasma lycopene concentration in people aged 65 y and over
      in a British national survey.
AB  - OBJECTIVE: Assessment of consumption of raw and processed tomatoes, plasma
      lycopene concentration and their interrelationship in a nationally representative
      sample of elderly British people. SETTING: : A 1994-1995 National Diet and
      Nutrition Survey: a nationwide cross-sectional sample of people aged 65 y and
      over living in mainland Britain, either in the community ("free-living", n=1275)
      or in institutions such as nursing homes (n=412). METHODS: Consumption of raw and
      processed tomatoes (including those in tomato-containing composite foods) was
      recorded by a 4-day dietary record for each participant. Plasma lycopene
      concentration was assayed by HPLC. Sociodemographic and lifestyle information was
      recorded by trained interviewers. RESULTS: In all, 29% of free-living people and
      24% of those living in institutions did not consume any raw or processed tomatoes
      during the 4-day recording period. Free-living participants were more likely to
      consume raw tomatoes (26 vs 16%). Plasma lycopene concentration was positively
      associated with the weight of raw and processed tomatoes consumed, especially
      with processed tomatoes and their products, alcohol consumption and with plasma
      total (as well as HDL and non-HDL) cholesterol concentrations. Among free-living
      participants, increased age, cigarette smoking habit and manual occupational
      social class were all associated with lower plasma lycopene concentration.
      CONCLUSIONS: In the current population, consumption of raw and processed tomatoes
      varied by sociodemographic and lifestyle characteristics, and made a significant
      contribution to plasma lycopene concentration. Determinants of plasma lycopene
      concentration were age, plasma cholesterol concentration and smoking habit.

PMID- 14647220
TI  - Association between antioxidant nutritional indicators and the incidence of
      dementia: results from the PAQUID prospective cohort study.
AB  - OBJECTIVE: To analyse the relation between antioxidant vitamins A, E, and
      malondialdehyde (MDA) lipoperoxidation product plasma concentrations with
      incident dementia. DESIGN: : A nested case-control within the PAQUID (Personnes
      Agees QUID) cohort. SETTING: The PAQUID population-based prospective cohort in
      southwestern France. SUBJECTS: Among 626 subjects with blood collection at
      baseline, 46 developed a dementia during the follow-up and were considered to be
      cases. Each case was matched (on age and sex) to three controls. RESULTS: Plasma
      vitamin E concentrations were lower among cases (mean value at 22.62 micromol/l
      (s.d.: 7.38) vs 24.99 (s.d.: 6.73 among controls). The same trend was observed
      for vitamin A concentrations, but the difference was not significant. On the
      contrary, MDA concentrations tended to be higher (mean value 1.35 micromol/l
      (s.d.: 0.53) vs 1.23 (s.d.: 0.44)) among cases. In logistic regression models,
      plasma values were split into tertiles. Adjusted for confounders, the risk of
      dementia was significantly increased in the lowest vitamin E tertile (< or =21.0
      micromol/l) (OR=3.12, P=0.033) compared to the highest one (> or =25.5
      micromol/l). The risk of Alzheimer's disease was also increased, with borderline
      significance (OR=3.06, P=0.053). Risks associated with vitamin A were
      nonsignificant. Similarly, there was a trend to an increased risk of dementia in
      the highest tertile of MDA (OR=1.67, P=0.31). CONCLUSIONS: These results suggest
      that subjects with low plasma vitamin E concentrations are at a higher risk of
      developing a dementia in subsequent years.

PMID- 14647221
TI  - Water and sanitation associated with improved child growth.
AB  - OBJECTIVE: To examine the relation between household water and sanitation, and
      the risk of stunting and reversal of stunting in Khartoum and Crezira regions,
      Sudan. DESIGN: Prospective cohort study. SETTING: A total of 25 483 children aged
      6-72 months from rural Sudan enrolled in an 18-month field trial in 1988 to study
      the effect of vitamin A supplementation on child health and survival. RESULTS:
      The mean height-for-age z-scores at baseline and the end of study were -1.66 and 
      1.55, respectively, for the group with water and sanitation facilities, and -2.03
      and -1.94 for the group without water and sanitation, after adjustment for age,
      region, gender, mother's literacy, intervention group (vitamin A vs placebo),
      family wealth, breastfeeding and cleanliness. Among children of normal height-for
      age at baseline, the risk of stunting (<-2 height-for-age z-score) was lowest in
      the group that came from homes that had both water and sanitation compared to
      children from homes without these facilities (multivariate RR=0.79, 95% CI 0.69
      0.90). Among children stunted at baseline, those coming from homes with water and
      sanitation had a 17% greater chance of reversing stunting than those coming from
      homes without either facility (adjusted RR=1.17, 95% CI 0.99-1.38). We did not
      detect a synergistic association between access to water and sanitation.
      CONCLUSIONS: Water and sanitation are independently associated with improved
      growth of children. SPONSORSHIP: None.

PMID- 14647222
TI  - Meal pattern, food choice, nutrient intake and lifestyle factors in The Goteborg
      Adolescence Study.
AB  - OBJECTIVE: To relate meal pattern of Swedish adolescents to food choice, nutrient
      intake and other lifestyle factors. DESIGN: Cross-sectional study including diet
      history and interview about smoking, ethnicity, social factors and
      retrospectively collected data of menarche and growth. SETTING: School setting,
      Goteborg, Sweden. SUBJECTS: A total of 611 boys and 634 girls in grade 9 (15-16
      y). RESULTS: The majority of the students, 65% of the boys and 52% of the girls,
      consumed three main meals daily. The in-between meals, however, contributed the
      major part of the energy intake. The energy intake was 12.9+/-3.5 MJ (mean+/
      s.d.) for boys and 9.0+/-2.5 MJ for girls. Irregular breakfast eating, 12% of the
      boys and 24% of the girls, was related to negative lifestyle factors where
      smoking was the strongest, odds ratio 3.8 (95% CI: 2.6-5.4) and to irregular
      intake of lunch and dinner. These boys and girls had a food choice including a
      higher percentage of energy from snack food (26% vs 20% and 19% in boys and girls
      respectively, all P<0.001), mostly consumed between the main meals. These groups
      had significantly lower intakes of micronutrients, but higher intakes of sucrose
      and alcohol compared to the groups with regular breakfast intake. Girls omitting
      breakfasts and lunches (8%) also had a less healthy food choice and the poorest
      nutrient intake. These girls had matured earlier, with menarche age of 12.2+/-1.1
      y vs 12.9+/-1.0 y (P<0.001) in girls with regular main meal intake. CONCLUSIONS:
      Meal pattern with omission of breakfast or breakfast and lunch was related to a
      clustering of less healthy lifestyle factors and food choice leading to a poorer
      nutrient intake. SPONSORSHIP: The Swedish Medical Research Council (project B94
      19X-04721-19A), the Swedish Mill Industry and the Wilhelm and Martina Lundgren
      Foundation.

PMID- 14647223
TI  - Recombinant human lactoferrin ingestion attenuates indomethacin-induced
      enteropathy in vivo in healthy volunteers.
AB  - OBJECTIVE: To determine whether recombinant human lactoferrin ingestion inhibits
      nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in
      healthy volunteers as a model for disorders associated with a rise in
      permeability of the stomach and the small intestine. DESIGN: A randomized
      crossover dietary intervention. SUBJECTS AND INTERVENTIONS: In all, 15 healthy
      volunteers (age 23+/-1.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R)
      permeability test was performed to assess gastroduodenal and small intestine
      permeability as indicator of NSAID-induced gastroenteropathy. All subjects
      consumed standardized meals for 2 days. On the second day at time=-24 h each
      subject ingested a drink containing 5 g recombinant human lactoferrin or placebo
      during breakfast. At t=-9 h, subjects ingested the same drink with 75 mg of the
      NSAID indomethacin and after an overnight fast at t=-1 h subjects consumed the
      drink and 50 mg indomethacin. After 1 h, at t=0, a permeability test was
      performed. RESULTS: Small intestine permeability after indomethacin and placebo
      was significantly higher (L/R ratio=0.036; 0.014-0.092, P<0.05) compared to the
      permeability observed after ingestion of indomethacin and lactoferrin (0.028;
      0.015-0.056), whereas gastroduodenal permeability did not differ between the two
      interventions (P=0.3). CONCLUSION: Oral recombinant human lactoferrin
      supplementation during a short-term indomethacin challenge reduced the NSAID
      mediated increase in small intestinal permeability and hence may provide a
      nutritional tool in the treatment of hyperpermeability-associated disorders.
      SPONSORSHIP: Grant and human recombinant lactoferrin donated from Agennix Inc.,
      Houston, TX.

PMID- 14647224
TI  - Sociodemographic differences in dietary habits described by food frequency
      questions--results from Denmark.
AB  - OBJECTIVES: To investigate whether a modest number of food frequency questions
      are sufficient to describe sociodemographic differences in dietary habits, and to
      identify sociodemographic characteristics of subjects adhering to food-based
      dietary guidelines operationalised in a "healthy-diet index". DESIGN: Cross
      sectional population survey. SUBJECTS: A total of 480 men, 515 women, aged 15-90
      y. Random sample of private telephone numbers drawn from regional telephone
      records, geographically stratified. Participation rate 62%. METHODS: Computer
      assisted telephone interviews, including six food frequency questions, a question
      on type of fat spreads used on bread, questions on seven sociodemographic
      variables. RESULTS: The summary of the healthy-diet index showed that the
      subjects who adhered to food-based dietary guidelines (top quintile) compared to
      those who did not (bottom quintile) were most often women (odds ratio (OR)=6.07;
      confidence interval (CI): 3.91-9.43, women vs men), of older age (OR=9.72; CI:
      3.02-31.31, old age vs young), highly educated (OR=3.69; CI: 1.53-8.92, high
      education vs low) and living in multiperson households including children
      (OR=4.66; CI: 2.47-8.80, multiperson household vs single household). The results
      also showed that gender difference in dietary habits is associated with other
      sociodemographic variables. CONCLUSIONS: The selected food frequency questions
      proved sufficient to describe sociodemographic differences in dietary habits, and
      this method may be a valuable supplement to traditional quantitative dietary
      surveys in monitoring sociodemographic changes in eating patterns. The results
      also underline the influence of sociodemographic status on dietary habits.
      SPONSORSHIP: The Danish Nutrition Council funded the study.

PMID- 14647225
TI  - Food insecurity is associated with dietary intake and body size of Korean
      children from low-income families in urban areas.
AB  - OBJECTIVE: This study examined household food insecurity of urban low-income
      families in Korea and the associations of the food insecurity with children's
      dietary intake and body size. DESIGN: Cross-sectional study. SETTING: Low-income
      neighborhoods in large cities. SUBJECTS: Included 370 children aged 4-12 y, who
      had all records on dietary intake and anthropometry as well as household food
      insecurity measures. RESULTS: Using the 10-item Radimer/Cornell Scale, 62.7% of
      the households showed some degree of food insecurity (8.6% for food insecure for
      family, 28.4% for food insecure for adults and 25.7% for child hunger
      households). Food insecurity was linearly and negatively associated with
      household economic conditions as well as the caretaker's use of nutrition
      knowledge. There were also significant associations of food insecurity with the
      children's dietary intakes, indicating the largest amount of nutrients for the
      children from the household food insecure, followed by those from the food
      secure, adult food insecure and child hunger groups. The household food insecure
      children were fatter than the food secure children. The fatter condition of the
      former children appeared to be related to more frequent intakes of low-quality
      foods. CONCLUSION: This study reports curvilinear associations between the status
      of household food insecurity and children's food intakes and fatness.
      SPONSORSHIP: This work was funded by a grant of the 2001 Korea Health Promotion
      Research Program, the Ministry of Health & Welfare, Republic of Korea.

PMID- 14647226
TI  - A practical approach to increasing intakes of n-3 polyunsaturated fatty acids:
      use of novel foods enriched with n-3 fats.
AB  - OBJECTIVES: To assess the effects of providing a wide range of foodstuffs
      containing n-3 polyunsaturated fatty acids (PUFA), occurring naturally or from
      fortification, on intake and blood and tissue proportions of n-3 PUFA. DESIGN:
      Before/after dietary intervention study. SETTING: Adelaide, Australia. SUBJECTS:
      16 healthy males recruited from the community. INTERVENTIONS: Subjects were
      provided with a range of foodstuffs naturally containing n-3 PUFA (fresh fish,
      canned fish, flaxseed meal, canola oil) and items fortified with fish oil
      (margarine spread, milk, sausages, luncheon meat, french onion dip). Food choices
      were left to the discretion of each subject. Intake was estimated by diet diary.
      Blood was collected at-2, 0, 2, and 4 weeks for fatty acid analysis. MAIN OUTCOME
      MEASURES: Dietary intakes; plasma, platelet, and mononuclear cell phospholipid
      fatty acids. RESULTS: Consumption of n-3 PUFA increased significantly: alpha
      linolenic acid (ALA) from 1.4 to 4.1 g/day (P<0.001), eicosapentaenoic acid (EPA)
      from 0.03 to 0.51 g/day (P<0.001), and docosahexaenoic acid (DHA) from 0.09 to
      1.01 g/day (P<0.001). Linoleic acid (LA) intake decreased from 13.1 to 9.2 g/day
      (P<0.001). The proportions of EPA and DHA increased significantly in all
      phospholipid pools examined; plasma EPA from 1.13% of total fatty acids to 3.38%
      (P<0.001) and DHA from 3.76 to 7.23% (P<0.001); mononuclear cell EPA from 0.40 to
      1.25% (P<0.001) and DHA from 2.33 to 4.08% (P<0.001); platelet EPA from 0.41 to
      1.2% (P<0.001) and DHA from 1.64 to 3.07% (P<0.001). CONCLUSION: Incorporating
      fish oil into a range of novel commercial foods provides the opportunity for
      wider public consumption of n-3 PUFA with their associated health benefits.
      SPONSORSHIP: Dawes Scholarship, Royal Adelaide Hospital.

PMID- 14647227
TI  - Serum fatty acid composition in primary school children is associated with serum
      cholesterol levels and dietary fat intake.
AB  - OBJECTIVE: To examine the serum fatty acid composition, serum cholesterol levels,
      and dietary fat intake associated with body composition in primary school
      children of both urban and rural regions in Taiwan. DESIGN: Subjects were
      randomly stratified by region and primary school. The sample consisted of 870
      children aged 10 and 11 y old. The sample was equally distributed between an
      urban region (Kaohsiung City) and a rural region (Yunlin County). The gender
      ratio of samples from each area was matched. Food record-assisted 24-h dietary
      recalls and serum lipid measurements were collected for each child, and
      associations between serum total cholesterol (TC) and fatty acids composition as
      well as between body mass index (BMI) and triceps skinfold (TSF) were evaluated
      for both urban and rural regions. RESULTS: Compared with students in the urban
      region, those in the rural region had significantly lower total fat intake, BMI,
      TSF, TC, and LDL cholesterol (LDL-C) and higher HDL-cholesterol (HDL-C) (P<0.05).
      Increased total fat (P<0.05) as a proportion of total energy was associated with
      increased TC and LDL-C. Lauric, myristic, and oleic acid levels in the serum of
      urban boys were significantly higher (P=0.0001, 0.0003, and 0.0398, respectively)
      than those of rural boys. In girls, the different fatty acid compositions
      affected TC concentrations, and palmitic and stearic acids of serum in the high
      TC group were significantly lower (P=0.0179 and 0.0001, respectively) than those
      in the low-TC group. CONCLUSIONS: Urban children had a dietary fat intake that
      both quantitatively and qualitatively differed from the traditional rural Chinese
      diet in Taiwan as reflected in rural children. Consumption of total fat was
      positively associated with BMI, TSF, TC, and LDL-C levels in Taiwanese children
      aged 10 and 11 y. SPONSORSHIP: This study was partly sponsored by a research
      grant from the Department of Health, Taiwan, ROC.

PMID- 14647228
TI  - Triacylglycerol markers of mature human milk.
AB  - OBJECTIVES: To determine which triacylglycerol (TAG) species in mature human milk
      are less affected by external factors and may thus be considered as TAG markers,
      as well as to determine which species are most influenced by these external
      conditions. Furthermore, we examine the correlation between the TAG markers and
      their fatty acids (FAs). SETTING AND SUBJECTS: Six healthy women from Barcelona
      (Catalonia, Spain). DESIGN AND INTERVENTIONS: In order to obtain the maximum
      variability of sampling conditions, 40 mature human milk samples were collected
      from different mothers, on different days, at different times of the day, and
      from different breasts during and after both the baby's and mother's meal. TAG
      and FA profiles were determined and correlated. The TAG composition was
      determined by high-performance liquid chromatography with an evaporative light
      scattering detector, and also with atmospheric pressure chemical ionisation mass
      spectrometry. FAs compositions were determined by gas chromatography. RESULTS:
      The results were analysed using the SPSS statistical package and proved to be
      more variable than might have been found in a more restrictive sample design.
      Nevertheless, despite these conditions, some TAG species were found in relatively
      constant levels in mature human milk, and could thus be considered as markers of
      the mature milk TAG profile. TAG species that we can classify in this group were:
      LaMO, CaPO, LaCaO, LaPCa, LaOL, MPLn, LLO, LaOO, MPL, and MOL. The names do not
      indicate the location of fatty acids in the glycerol molecule. On the other hand,
      concentrations of other TAG species vary considerably between samples and
      consequently these may be understood to be especially affected by the external
      factors. TAGs like PaLS, MPO, PaOO, PPP, MPS, SPP, LOO, PPO, MOS, SSP, POL, and
      SOS are in this second group. Correlation between the TAG markers and their FAs
      was examined by Pearson's test and a significant correlation was found for some
      FAs. CONCLUSIONS: The TAG species present in mature human milk are affected in
      different ways by external factors such as dietary intake, nutritional status,
      length of lactation, time of the day, etc. Some TAGs may be considered as markers
      of mature human milk as they are relatively constant under a wide range of
      sampling conditions and do not depend on the factors mentioned. SPONSORSHIP: This
      study was supported by the Fundacio Mestres Jane.

PMID- 14647229
TI  - Risk factors for nightblindness among women of childbearing age in Cambodia.
AB  - OBJECTIVE: To characterize risk factors for nightblindness among nonpregnant
      women of childbearing age, a group recently recognized to be at high risk of
      vitamin A deficiency in some developing countries. DESIGN: Case-control study.
      SETTING: The study included >15 000 households in National Micronutrient Survey
      of Cambodia conducted in 2000. SUBJECTS: The prevalence of nightblindness among
      13 358 nonpregnant women was 2.0%. A total of 328 nonpregnant women with
      nightblindness were matched by province with 1009 nonpregnant women without
      nightblindness. METHODS: Univariate and multivariate logistic regression models
      were used to estimate odds ratios (ORs) as estimates of the relative risk of
      factors associated with nightblindness. RESULTS: In a final model, materials in
      the wall of the house (OR 1.4, 95% confidence interval (CI) 0.9-2.0), land
      ownership < or =0.5 hectares (OR 1.4, 95% CI 1.0-1.9), nightblindness in last
      pregnancy (OR 44.5, 95% CI 29.2-67.8), parity >3 (OR 1.5, 95% CI 1.0-2.1),
      diarrhea within the last 2 weeks (OR 1.9, 95% CI 1.3-2.8), maternal body mass
      index <18.5 (OR 1.8, 95% CI 1.2-2.7), and lack of consumption of vitamin A-rich
      animal foods in the last 24 h (1-60 retinol equivalents (RE) OR 1.1, 95% CI 0.7
      1.6; > or =60 RE, OR 0.7, 95% CI 0.4-1.0) were associated with nightblindness
      among nonpregnant women. CONCLUSIONS: Women of childbearing age in Cambodia with
      low socioeconomic status, low consumption of vitamin A-rich animal foods, a
      history of nightblindness during the previous pregnancy, parity >3, malnutrition,
      and diarrhea have a higher risk of nightblindness. SPONSORSHIP: United States
      Agency for International Development (442-G-00-95-00515-00).

PMID- 14647230
TI  - Breast milk and energy intake in exclusively, predominantly, and partially breast
      fed infants.
AB  - OBJECTIVE: To investigate the extent to which breast milk is replaced by intake
      of other liquids or foods, and to estimate energy intake of infants defined as
      exclusively (EBF), predominantly (PBF) and partially breast-fed (PartBF). DESIGN:
      Cross-sectional. SETTING: Community-based study in urban Pelotas, Southern
      Brazil. SUBJECTS: A total of 70 infants aged 4 months recruited at birth. MAIN
      OUTCOME MEASURES: Breast milk intake measured using a "dose-to-the-mother"
      deuterium-oxide turnover method; feeding pattern and macronutrient intake
      assessed using a frequency questionnaire. RESULTS: Adjusted mean breast milk
      intakes were not different between EBF and PBF (EBF, 806 g/day vs PBF, 778 g/day,
      P=0.59). The difference between EBF and PartBF was significant (PartBF, 603
      g/day, P=0.004). Mean intakes of water from supplements were 10 g/day (EBF), 134
      g/day (PBF) and 395 g/day (PartBF). Compared to EBF these differences were
      significant (EBF vs PBF, P=0.005; EBF vs PartBF, P<0.001). The energy intake of
      infants receiving cow or formula milk (BF+CM/FM) in addition to breast milk
      tended to be 20% higher than the energy intake of EBF infants (EBF, 347 kJ/kg/day
      vs BF+CM/FM, 418 kJ/kg/day, P=0.11). CONCLUSIONS: There was no evidence that
      breast milk was replaced by water, tea or juice in PBF compared to EBF infants.
      The energy intake in BF+CM/FM infants tended to be 20% above the latest
      recommendations (1996) for breast-fed and 9% above those for formula-fed infants.
      If high intakes are maintained, this may result in obesity later in life.
      SPONSORSHIP: International Atomic Energy Agency through RC 10981/R1.

PMID- 14647231
TI  - Energy intake in Swedish adolescents: validation of diet history with doubly
      labelled water.
AB  - OBJECTIVE: To compare habitual energy intake (EI) estimated from diet history
      (DH) with total energy expenditure (TEE) measured with doubly labelled water
      (DLW) in adolescents. DESIGN: DH included a detailed questionnaire and an
      interview. TEE was measured during a 14-day period. Adequate (AR), under- (UR)
      and over-reporters (OR) were defined from the ratio EI/TEE: AR 0.84-1.16, UR
      <0.84 and OR >1.16. SETTING: Participants were recruited from grade 9 in a
      compulsory school in Goteborg, Sweden. All data were collected at school and DLW
      dosages were distributed at Sahlgrenska University Hospital. SUBJECTS: A total of
      35 adolescents (18 boys, 17 girls), 15.7 (0.4) y. RESULTS: EI was 11.0 (3.6) MJ
      and TEE was 11.4 (2.1) MJ (P=0.42). DH was able to rank EI compared to TEE
      (Spearman's r=0.59, P< or =0.001). For girls, EI was 18% lower (P=0.0067) and for
      boys, EI was 7% higher (P=0.26) compared to TEE. The 95% limits of agreement for
      difference between TEE and EI were -5.6 to 6.5 MJ. In total, 20 subjects were
      defined as AR (57%), nine as UR (26%) and six as OR (17%). Energy from in-between
      meals was 33% lower (P=0.0043) in UR girls and 57% higher (P=0.026) in OR boys,
      compared to adequate reporting girls and boys, respectively. In UR girls, energy
      adjusted intake (10 MJ) of specific foods did not differ significantly, fat was
      lower and carbohydrate and vitamin C were higher compared to AR girls (all
      P<0.05). OR boys had no significant differences in food and nutrient intake in 10
      MJ compared to AR boys. CONCLUSION: The diet history was able to capture EI for
      the group and to rank subjects. There was a wide individual range in reporting
      accuracy related to gender. SPONSORSHIP: The Ingabritt and Arne Lundberg
      Foundation, The Wilhelm and Martina Lundgren Foundation.

PMID- 14647232
TI  - Downregulation of osteopontin and bone sialoprotein II is related to reduced
      colony formation and metastasis formation of MDA-MB-231 human breast cancer
      cells.
AB  - Osteopontin (OPN), bone sialoprotein (BSPII), and osteonectin (ON) belong to a
      family of glycoproteins, which have been linked to cancer metastasis and
      progression. Here, we report on the selection of antisense oligonucleotides
      (ASOs), which are effective in reducing their protein levels. In human MDA-MB-231
      breast cancer cells, the maximum inhibition of protein expression ranged from 84%
      (OPN) to 75% (BSPII) and 70% (ON). Erucylphospho-NNN-trimethylpropanolamine
      (ErPC3) was used as positive control and combination partner. Exposure to ErPC3
      inhibited colony formation of MDA-MB-231 cells by 11% (10 microM), 45% (14
      microM) and 78% (20 microM). The clonogenicity of breast cancer cells was reduced
      by 15%, 11%, 8% (5 microM), 39%, 19%, 14% (10 microM) and 46%, 39%, 21% (20
      microM) in response to ASO-OPN-04, ASO-BSPII-06 and ASO-ON-03, respectively.
      Combination of ErPC3 with the ASOs caused additive combination effects. Pre
      exposure to the ASOs, but not to the NSO, inhibited formation of osteolytic
      metastasis in three of four (ASO-OPN-04, P<0.03) and two of four (ASO-BSPII-06)
      nude rats, and reduced metastasis lesions significantly (T/C%=4.3 and 9.1,
      P=0.05, respectively). We conclude that downregulation of OPN and BSPII reduces
      colony formation of MDA-MB-231 cells and formation of osteolytic metastasis in
      nude rats.

PMID- 14647233
TI  - Concurrent delivery of tumor antigens and activation signals to dendritic cells
      by irradiated CD40 ligand-transfected tumor cells resulted in efficient
      activation of specific CD8+ T cells.
AB  - To improve the efficacy of tumor cell-based and dendritic cell (DC)-based cancer
      vaccines, this study explored the potential of a new cancer vaccine strategy,
      that is, the use of CD40 ligand-transfected tumor (CD40L-tumor) cells to
      simultaneously deliver both tumor-derived antigens (Ag) and maturation stimuli to
      DCs. Materials from frozen/thawed or irradiated human tumor cells, with or
      without surface CD40L, were internalized efficiently by immature DCs after
      coincubation. However, during the internalization process, only coculturing with
      irradiated CD40L-tumor cells resulted in concurrent, optimal DC maturation and
      production of proinflammatory chemokines and pro-Th1 cytokines, such as IL-6, IL
      8, IL-12, IFN-gamma, and TNF-alpha. These activated DCs were the most potent
      cells to support the growth of CD8+, IFN-gamma-producing T cells, and to process
      tumor Ag for the generation of specific cytotoxic T cells in vitro. Animals
      vaccinated with irradiated CD40L-tumor cell-pulsed DCs were better protected
      against subsequent challenge of a weakly immunogenic tumor cell line than animals
      vaccinated with irradiated CD40L-tumor cells alone. Thus, our results strongly
      support the future clinical application of using DCs pulsed with irradiated CD40L
      tumor cells as a cancer vaccine.

PMID- 14647234
TI  - Lysosomes and mitochondria in the commitment to apoptosis: a potential role for
      cathepsin D and AIF.

PMID- 14647235
TI  - Caspases: an ancient cellular sword of Damocles.
AB  - Caspases are a family of cysteine proteases homologous to the Caenorhabditis
      elegans programmed cell death gene product CED-3. Caspases and their distant
      relatives, meta- and paracaspases, have been found in phylogenetically distant
      nonmetazoan groups, including plants, fungi and prokaryotes. This review
      summarizes the current information on the mechanisms and functions of non
      mammalian caspases and their relatives in apoptotic and nonapoptotic processes,
      and explores the possible evolutionary origin of the caspase family.

PMID- 14647236
TI  - Cell cycle molecules and vertebrate neuron death: E2F at the hub.
AB  - Vertebrate neuron cell death is both a normal developmental process and the
      catastrophic outcome of nervous system trauma or degenerative disorders. Although
      the mechanisms of such death include an evolutionarily conserved core apoptotic
      pathway that is highly homologous to that first described by Horvitz and co
      workers in Caenorhabditis elegans, it appears that many instances of neuron death
      additionally require the transcription-dependent induction of proapoptotic
      molecules. One such proapoptotic transcriptional pathway revealed by studies over
      the past decade revolves about the transcription factor E2F and those molecules
      that either regulate E2F activity or that are direct or indirect transcriptional
      targets of E2F. Many of the molecules associated with the E2F apoptotic pathway
      in postmitotic neurons also participate in the cell cycle in proliferating cells.
      Observations in human material and in animal and cell culture models show
      widespread correlation between changes in expression, activity and subcellular
      localization of E2F-related cell cycle molecules and developmental and
      catastrophic neuron death. A variety of experimental approaches support a causal
      role for such changes in the death process and are beginning to indicate how the
      neuronal E2F pathway activates the core apoptotic machinery. The discovery and
      elaboration of the neuronal apoptotic E2F pathway provides abundant targets as
      well as small molecule candidates for potential therapeutic intervention in
      nervous system trauma and degenerative disease.

PMID- 14647237
TI  - Paradigm shift in neuroprotective drug development: clinically tolerated NMDA
      receptor inhibition by memantine.

PMID- 14647239
TI  - Men are but worms: neuronal cell death in C elegans and vertebrates.
AB  - Awarding the 2002 Nobel Prize in Physiology or Medicine to Sydney Brenner, H
      Robert Horvitz, and John E Sulston for 'their discoveries concerning the genetic
      regulation of organ development and programmed cell death (PCD)' highlights the
      significant contribution that the study of experimental organisms, such as the
      nematode Caenorhabditis elegans, has made to our understanding of human
      physiology and pathophysiology. Their studies of lineage determination in worms
      established the 'central dogma' of apoptosis: The BH3-only protein EGL-1 is
      induced in cells destined to die, interacts with the BCL-2-like inhibitor CED-9,
      displacing the adaptor CED-4, which then promotes activation of the caspase CED
      3. The vast majority of cells undergoing PCD during development in C. elegans, as
      in vertebrates, are neurons. Accordingly, the genetic regulation of apoptosis is
      strikingly similar in nematode and vertebrate neurons. This review summarizes
      these similarities - and the important differences - in the molecular mechanisms
      responsible for neuronal PCD in C. elegans and vertebrates, and examines the
      implications that our understanding of physiological neuronal apoptosis may have
      for the diagnosis and treatment of acute and chronic human neurodegenerative
      disorders.

PMID- 14647238
TI  - Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma
      cells.
AB  - Fenretinide (HPR), a synthetic retinoid that exhibits lower toxicity than other
      retinoids, has shown preventive and therapeutic activity against ovarian tumors.
      Although the growth inhibitory effects of HPR have been ascribed to its ability
      to induce apoptosis, little is known about the molecular mechanisms involved.
      Since the proto-oncogene c-Fos has been implicated in apoptosis induction, we
      analyzed its role in mediating HPR response in a human ovarian carcinoma cell
      line (A2780) sensitive to HPR apoptotic effect. In these cells, HPR treatment
      caused induction of c-Fos expression, whereas such an effect was not observed in
      cells made resistant to HPR-induced apoptosis (A2780/HPR). Moreover, in a panel
      of other human ovarian carcinoma cell lines, c-Fos inducibility and HPR
      sensitivity were closely associated. Ceramide, which is involved in HPR-induced
      apoptosis, was also involved in c-Fos induction because its upregulation by HPR
      was reduced by fumonisin B(1), a ceramide synthase inhibitor. The causal
      relationship between c-Fos induction and apoptosis was established by the finding
      of an increased apoptotic rate in cells overexpressing c-Fos. Similarly to that
      observed for c-Fos expression, HPR treatment increased c-Jun expression in HPR
      sensitive but not in HPR-resistant cells, suggesting the involvement of the
      transcription factor activating protein 1 (AP-1) in HPR-induced apoptosis. In
      gene reporter experiments, HPR stimulated AP-1 transcriptional activity and
      potentiated the AP-1 activity induced by 12-tetradecanoylphorbol 13-acetate.
      Furthermore, inhibition of AP-1 DNA binding, by transfecting A2780 cells with a
      dominant-negative Fos gene, caused decreased sensitivity to HPR apoptotic
      effects. Overall, the results indicate that c-Fos plays a role in mediating HPR
      induced growth inhibition and apoptosis in ovarian cancer cells and suggest that
      c-Fos regulates these processes as a member of the AP-1 transcription factor.

PMID- 14647240
TI  - Looking for death at the core of life in the light of evolution.

PMID- 14647241
TI  - Involvement of cell cycle progression in survival signaling through CD40 in the B
      lymphocyte line WEHI-231.
AB  - The CD40 molecule transmits a signal that abrogates apoptosis induced by ligation
      of the antigen receptor (BCR) in both primary B cells and B-cell lines such as
      WEHI-231. Expression of Bcl-xL and A1, antiapoptotic members of the Bcl-2 family,
      is enhanced by CD40 ligation, and is suggested to mediate CD40-induced B-cell
      survival. CD40 ligation also promotes cell cycle progression by increasing the
      levels of cyclin-dependent kinases (CDKs) required for cell cycle progression,
      and reducing expression of the CDK inhibitor p27(kip1). Here we demonstrate that
      cell cycle inhibition by retrovirus-mediated p27(kip1) expression does not
      modulate the levels of Bcl-xL or A1, but significantly reduces the survival of
      BCR-ligated WEHI-231 cells by CD40 ligation. This indicates that cell cycle
      progression is crucial for CD40-mediated survival of B cells.

PMID- 14647242
TI  - Ideal or actual body weight to calculate CD34+ cell doses for allogeneic
      hematopoietic stem cell transplantation?
AB  - The number of CD34+ cells infused influences hematologic recovery after
      transplantation. Limited data suggest that cell dose should be based on ideal
      (IBW) rather than actual (ABW) body weight for autotransplantation, but none in
      allografts. We compared the correlation between recovery to 0.5 x 10(9)/l
      neutrophils and the CD34+ cell dose based upon ABW and IBW in 78 allograft
      recipients. ABW was > or =25% over IBW in 47% of patients. The median CD34+ cell
      dose was 5.1 x 10(6)/kg IBW and 4.4 x 10(6)/kg ABW. The time to neutrophil
      recovery was 8-26 days (median 12). There was a stronger inverse correlation
      between CD34+ cell dose/IBW and neutrophil recovery (r(2)=0.160; P<0.0001) than
      between CD34+ cell dose/ABW and neutrophil recovery (r(2)=0.138; P=0.001). When
      neutrophil recovery in patients receiving <3 or <5 x 10(6) CD34+ cells/kg was
      compared to those receiving > or =3 or > or =5 x 10(6) CD34+ cells/kg,
      respectively, separately by IBW and ABW, the magnitude and significance of the
      differences were greater for IBW-based comparisons. These data suggest the CD34+
      cell dose based on IBW is a better predictor of neutrophil recovery after
      allografting. Further work in a larger, more homogeneous group of patients is
      required to confirm this observation.

PMID- 14647243
TI  - Pharmacokinetics of high-dose chemotherapy.
AB  - There is considerable variation in the severity of preparative regimen-related
      toxicity (RRT) in hematopoietic stem-cell transplantation (HSCT). This variation
      has been recognized to be due, in part, to the wide variation in the
      pharmacokinetics (PK) of high-dose chemotherapy (HDC). Consequently, therapeutic
      drug modeling and pharmacokinetic-directed therapy (PKDT) represents an
      attractive strategy in this setting. Advances in our understanding of drug
      metabolism, the nature of the active metabolites, and the ability to measure drug
      concentrations have led to the point where for some agents it is now possible to
      treat to a given PK end point with a great deal of reliability. In-depth
      knowledge of the PK and pharmacodynamics (PD) associations of the agents employed
      in the high-dose setting will make possible more efficient research into
      preparative regimen dosing intensity and comparisons of different preparative
      regimens as well as safer HSCT overall. In this review, we discuss PK and PD
      studies of high-dose cyclosphamide, melphalan, thiotepa, carmustine, cisplatin,
      carboplatin, paclitaxel, docetaxel, and busulfan.

PMID- 14647244
TI  - Successful reduced-intensity HLA-haploidentical stem cell transplantation based
      on the concept of feto-maternal tolerance for an elderly patient with
      myelodysplastic syndrome.

PMID- 14647245
TI  - Transplantation of CD34+ enriched allografts in children with nonmalignant
      diseases: does graft manipulation necessarily result in high incidence of graft
      failure?

PMID- 14647246
TI  - Infections among allogeneic bone marrow transplant recipients in India.
AB  - SUMMARY: Infections are a major cause of morbidity and mortality in patients
      undergoing high-dose therapy and allogeneic bone marrow transplantation (BMT)
      despite prophylaxis, use of growth factors and newer antimicrobial drugs. We
      report the clinical profile of infections among 297 patients who underwent 304
      allogeneic transplants between 1986 and December 2001. All patients developed
      febrile neutropenia. There were 415 documented infections among 304 transplants.
      This included bacterial (34.9%), viral (42.9%), fungal (15.9%) and other
      infections (6.3%) including tuberculosis. Bacterial pathogens were mainly Gram
      negative bacteria (80%) as compared to Gram-positive (20%) bacteria. The common
      Gram-negative bacteria were nonfermenting Gram-negative bacteria (NFGNB) (24.9%),
      Pseudomonas (17.9%), Escherichia coli (17.9%) and Klebsiella (9.7%). The major
      source of positive cultures was blood (53.7%) followed by urine (25.5%) and
      sputum (8.9%). In all, 133/304 (43.7%) transplants had 178 documented viral
      infections. The common viral infections were due to cytomegalovirus, herpes group
      of viruses and transfusion-related hepatitis; and 60/304 (19.7%) transplants had
      66 documented fungal infections. Common fungi included Aspergillus species
      (69.7%), Candida (22.2%) and Zygomycetes (8.1%). Tuberculosis was documented in
      2.3% of the transplants. Catheter infections were suspected or documented in 7.8%
      of the transplants (24/304). The incidence of infections in this series from
      developing countries is not significantly different from reports from the West.
      Bone Marrow Transplantation (2004) 33, 311-315. doi:10.1038/sj.bmt.1704347
      Published online 1 December 2003

PMID- 14647247
TI  - Quality of life in adults following bone marrow transplantation during childhood.
AB  - SUMMARY: Quality of life (QOL) was assessed in 22 young adults, 14 years - on
      average- after having received bone marrow transplantation (BMT) during childhood
      at the Leiden University Medical Center. All were disease-free and >16 years when
      interviewed. The sickness impact profile and the Medical Outcome Study 36-item
      Short Form Health Survey were used as generic questionnaires in the assessment of
      QOL. The Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale
      (FACT-BMT) was used as a disease-specific measure of QOL. Coping was assessed by
      means of the Utrecht coping list. BMT-related variables were obtained from
      medical files. Of the generic QOL measures, most results fell within the normal
      range of functioning, although some illness-related impairment was reported on
      subscales for general and work-related functioning. Compared to a reference
      sample of patients who had received BMT as adults, patients involved in this
      study scored significantly higher on the 'emotional well-being' subscale of the
      FACT-BMT, indicating significantly better emotional functioning. The age at BMT
      and total body irradiation (TBI) were not related to patients' QOL. We can
      conclude that at long term, having received BMT during childhood does not
      negatively affect the QOL of patients. Bone Marrow Transplantation (2004) 33, 329
      336. doi:10.1038/sj.bmt.1704345 Published online 1 December 2003

PMID- 14647248
TI  - Autologous stem cell transplantation in primary systemic amyloidosis: the impact
      of selection criteria on outcome.
AB  - Autologous stem cell transplantation (ASCT) for primary systemic amyloidosis (AL)
      produces high hematologic and organ responses. However, treatment-related
      mortality remains high and reported series are subject to selection bias. In all,
      48 of 80 amyloid patients referred to our center had AL in the absence of
      myeloma, 26 of these 48 were deemed transplant candidates and 20 actually
      underwent ASCT. Transplant-related mortality has fallen from 50 to 20% since
      January 1999 due to better patient selection and prophylactic measures. Intent-to
      treat organ responses were renal (46%), cardiac (25%) and liver (50%). Organ
      responses in patients who survived transplantation were renal (75%), cardiac
      (40%) and liver (100%). The 3-year OS post-ASCT was 56% with improved outcome
      predicted by a better performance status (P=0.08), normal ALP (P=0.08), nephrotic
      syndrome (P=0.01) and the absence of severe hypotension (P=0.01). The 3-year OS
      for all referred patients was 44% and this was not significantly better for
      transplant candidates. Patients with significant hypotension (systolic blood
      pressure < or =90 mmHg) or poor performance status (ECOG >2) have an exceedingly
      high treatment-related mortality and should not be transplanted. For those
      undergoing ASCT, organ response rates appear promising, but conclusive evidence
      of improved survival for this select group of patients is still lacking and will
      require randomized trials.

PMID- 14647249
TI  - Herpes simplex virus infection in adult patients after unrelated cord blood
      transplantation: a single-institute experience in Japan.
AB  - Herpes simplex virus (HSV) infection in adult patients who underwent cord blood
      transplantation (CBT) from unrelated donors was studied. None of nine HSV
      seronegative patients developed HSV disease after CBT. Of 28 HSV-seropositive
      patients, seven (25%) developed HSV disease at a median of 92 days after CBT
      (range, 52-239 days). The cumulative incidence of HSV disease in HSV-seropositive
      patients was 27% at 12 months after CBT. The manifestations of HSV disease
      included gingivostomatitis (three patients), herpes labialis (two patients),
      localized herpes facialis of the nose (one patient), and disseminated eczema
      herpeticum (one patient). HSV disease recurred in two patients as
      gingivostomatitis and disseminated eczema herpeticum. All the patients responded
      to antiviral therapy. The presence of grade II-IV acute graft-versus-host disease
      (GVHD) was significantly associated with a higher rate of HSV disease after CBT
      (51 vs 8%, P=0.015). These results suggest that the recovery of HSV-specific
      immune responses is delayed in patients who develop grade II-IV acute GVHD after
      CBT.

PMID- 14647250
TI  - Allogeneic peripheral blood stem cell transplantation from two- or three-loci
      mismatched related donors in adult Japanese patients with high-risk hematologic
      malignancies.
AB  - With the increasing frequency of haploidentical transplantation, it is becoming
      more important to establish the degree of HLA mismatch that can be accepted. We
      retrospectively analyzed clinical data of 50 adult Japanese patients with high
      risk hematologic malignancies who underwent allogeneic peripheral blood stem cell
      transplantation (PBSCT) from two- or three-loci-mismatched related donors with
      HLA class I and II gene disparities in the graft-versus-host direction. They were
      treated at 20 transplant centers between 1996 and 2002. In all, 18 patients
      received unmanipulated PBSC, while 32 received purified CD34+ blood cells.
      Conventional (n=31) or reduced-intensity (n=19) conditioning regimens were used.
      Of the 39 patients (78%) who survived for > or =28 days after transplant, 37
      (95%) achieved neutrophil engraftment, while graft failure and rejection occurred
      in two of 39 (5%) and three of 37 (8%) patients, respectively. Stepwise Cox
      regression analysis revealed a significantly lower incidence of grades II-IV
      acute GVHD in patients receiving purified CD34+ cells (hazard ratio 0.32; 95% CI
      0.12-0.84; P=0.022). By 1 year post transplant, 28 patients (56%) had died of
      transplant-related problems, including infectious complications (30%). Although
      the number of patients is small, our data suggest that transplant-related
      problems, particularly infectious complications, are major obstacles to the
      success of this therapy.

PMID- 14647251
TI  - Administration of granulocyte-colony-stimulating factor for allogeneic
      hematopoietic cell collection may induce the tissue factor-dependent pathway in
      healthy donors.
AB  - The hypercoagulable state caused by the use of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) has been cited in anecdotal reports. Since
      tissue factor (TF) is the main initiator of the coagulation cascade, we examined
      if rhG-CSF had an inductive effect on the TF-dependent pathway in 18 healthy
      donors receiving rhG-CSF (10 microg/kg/day x 5 days) for peripheral blood
      progenitor cell mobilization. After rhG-CSF, there were increases both in TF
      antigen (TF:Ag) (P=0.01) and TF procoagulant activity (TF:PCA) (P=0.06) plasma
      levels and in TF:Ag cytofluorimetric expression on CD33 (+) cells (P=0.04). Mean
      activities of FVIII and vWF also increased significantly. Thrombin time was
      slightly prolonged (P=0.06) due to significant increases in plasma D-dimer
      levels. In addition, while FIX activity remained stable, there were marked
      reductions in mean plasma FX and FII activities and a slight decrease in FVII
      activity that resulted in a significant prolongation of prothrombin time within
      normal ranges. In conclusion, the administration of rhG-CSF led to a
      "prothrombotic state" via stimulation of TF and increased endothelial markers,
      such as F VIII and vWF. In the light of these findings, the use of rhG-CSF for
      stem cell mobilization should be undertaken cautiously in healthy donors with
      underlying thrombotic risk factors.

PMID- 14647252
TI  - Gram-negative bacteraemia (GNB) after 428 unrelated donor bone marrow transplants
      (UD-BMT): risk factors, prophylaxis, therapy and outcome.
AB  - Gram-negative infection is an important cause of morbidity and mortality after
      unrelated donor-bone marrow transplantation (UD-BMT). We performed a
      retrospective case-control study to examine the risk factors, prophylaxis,
      therapy and outcome of Gram-negative bacteraemia (GNB) in 428 patients undergoing
      UD-BMT. The incidence of GNB was 3.6% in children and 19% in adults. Of the
      adults, 11% developed GNB >60 days post UD-BMT. Predisposing risk factors for GNB
      included 'high-risk' disease status, chronic graft-versus-host disease and use of
      systemic steroids. Fever, a raised C-reactive protein (CRP) and hypotension were
      common findings at presentation. Patients were routinely given prophylactic
      ciprofloxacin: resistance to this antibiotic was seen in 33% of isolates. We
      identified an age-matched control group undergoing UD-BMT over the same time
      period as the study group. Gram-positive bacteraemia was significantly more
      common in cases than controls. Mortality from GNB was 17% in children and 24% in
      adults. We conclude that GNB is a common complication of UD-BMT with a high
      associated mortality. Patients should be educated further to present rapidly with
      symptoms suggestive of infection.

PMID- 14647253
TI  - Clinical relevance of serial quantitative analysis of hematopoietic chimerism
      after allogeneic stem cell transplantation in children for severe aplastic
      anemia.
AB  - Allogeneic stem cell transplantation (allo-SCT) is a well-established treatment
      modality for children with severe aplastic anemia (SAA). Treatment failures are
      rare and mostly caused by graft rejection. Increasing mixed chimerism represents
      a stage at the very beginning of graft rejection, where immunological
      intervention might be an effective prophylactic approach. To substantiate this,
      we: (1) monitored peripheral blood cells from children with SAA after allo-SCT
      and performed pre-emptive immunotherapy in patients with increasing MC. In all,
      23/34 courses of 32 children with SAA after allo-SCT showed a complete chimerism
      (CC) throughout and 10/34 developed different types of mixed chimerism (MC).
      Altogether, 4/10 with MC spontaneously developed decreasing MC, 2/10 courses
      persisted with low proportions of autologous cells below 30% (stable-MC), 4/10
      developed increasing MC and one patient showed an autologous recovery. All
      patients with CC, decreasing MC or stable MC remained in continuous complete
      remission (CCR). In all, 2/4 patients with increasing MC developed graft
      rejection. Based on these observations, 2/4 new patients with increasing MC
      received low-dose DLIs prophylactically, and remained in CCR without any GVHD.
      These results substantiate that low-dose DLI in children with SAA and increasing
      MC can prevent graft rejection with a calculable risk to induce severe GVHD.

PMID- 14647254
TI  - Efficacy of donor vaccination before hematopoietic cell transplantation and
      recipient vaccination both before and early after transplantation.
AB  - Allogeneic hematopoietic cell transplantation is followed by humoral
      immunodeficiency. We evaluated whether antibody levels can be improved by
      recipient vaccination on day -1 and 50 and whether the levels can be further
      improved by donor vaccination on day -20. A total of 85 patients were randomized
      or assigned to one of the following strategies of immunization with Streptococcus
      pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein
      conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface
      antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50
      and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365
      (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)). For H.
      influenzae and tetanus, IgG levels after grafting were the highest in the D(
      20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the
      lowest in the D(N)R(365) patients. For S. pneumoniae and hepatitis B, antibody
      levels appeared to be similar in all three patient groups. The results suggest
      that for polysaccharide-protein conjugate antigens or protein recall antigens,
      recipient immunization on days -1 and 50 improves antibody levels and that donor
      vaccination on day -20 further improves the levels. In contrast, neither
      recipient immunization on days -1 and 50 nor donor immunization on day -20
      appears to be efficacious for polysaccharide antigens and poorly immunogenic
      protein neo-antigens.

PMID- 14647255
TI  - Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation.
AB  - In the present study, we analyze the efficacy of prophylaxis with meropenem in
      patients receiving a matched related donor allogeneic transplant. In total, 38
      patients were sequentially treated with meropenem starting on the day of the
      first febrile episode (n=17, group A) vs prophylactic meropenem starting on the
      first day with <500/mm(3) granulocytes (n=21, group B), and maintained until
      resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%)
      patients in group A developed fever as compared to 16 (76%) in group B (P=0.02).
      While only one patient in group A did not require first-line antibiotherapy,
      there were seven (33%) in group B who did not require it (P=0.01) since fever
      lasted less than 72 h. In addition, 52% patients in group B did not require
      second-line antibiotics as compared to 11% among patients in group A (P=0.04). In
      multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02);
      P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04
      0.62); P=0.04) significantly influenced the development of fever. In conclusion,
      the current pilot study suggests that the use of prophylaxis with meropenem
      during the period of neutropenia in patients undergoing allogeneic
      transplantation favorably affects the morbidity of the procedure by reducing
      febrile episodes.

PMID- 14647256
TI  - Influence of cytomegalovirus (CMV) sero-positivity on CMV infection, lymphocyte
      recovery and non-CMV infections following T-cell-depleted allogeneic stem cell
      transplantation: a comparison between two T-cell depletion regimens.
AB  - We compared the incidence and outcome of preemptively treated cytomegalovirus
      (CMV) infection, lymphocyte recovery and non-CMV infections between two different
      TCD modalities, one employing CD34+ selection and T-cell add-back (TCAB),
      preceded by Campath-1H in vivo (CD34+/TCAB group, n=29), and the other using
      grafts incubated with Campath-1H in vitro (Campath-1H in vitro group, n=32). The
      probabilities of CMV reactivation and recurrence were 67 and 83.6% in the
      CD34+/TCAB group and 42.9 and 20% in the Campath-1H group (P=0.07 and 0.02).
      Donor sero-positivity reduced CMV reactivation in the Campath-1H group, but not
      in the CD34+/TCAB group. The durations of positive PCR/antigenemia positivity and
      antiviral therapy were also significantly longer in the CD34+/TCAB group.
      However, only two patients developed CMV disease in each group. The mean absolute
      lymphocyte counts (x 10(9)/l) at 30 days (0.27 vs 0.4, P=0.03) and 100 days (0.77
      vs 1.4, P=0.01) were significantly lower in the CD34+/TCAB group along with a
      higher incidence of non-CMV infections in CMV at-risk patients, but not in the
      CMV low-risk group. These findings suggest that the modality of TCD should be
      tailored according to the CMV risk status, and CMV sero-positive patients should
      receive a less extensively T-cell-depleted graft and a CMV sero-positive graft if
      possible.

PMID- 14647257
TI  - Nonmyeloablative allogenic peripheral-blood stem-cell transplantation in
      pancreatic adenocarcinoma: one case, high expectations.

PMID- 14647258
TI  - A pilot study of cytoreductive chemotherapy combined with infusion of additional
      peripheral blood stem cells reserved at time of harvest for transplantation in
      case of relapsed hematologic malignancies after allogeneic peripheral blood stem
      cell transplant.
AB  - Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is
      inconvenient and occasionally impossible in case of unrelated donors. It is well
      known that the effect of a growth factor-primed DLI is comparable to that of a
      nonprimed DLI. In total, 42 patients with hematologic malignancies and a high
      risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood
      stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at
      the time of harvest, additional peripheral blood stem cells (PBSCs) were also
      reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who
      relapsed after allogeneic PBSCT were treated with mainly cytarabine-based
      chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+
      and CD34+ cells for the primed DLIs was 1.43 x 10(8)/kg and 4.75 x 10(6)/kg,
      respectively. Six of the 12 relapsed patients exhibited a complete response after
      the primed DLI, plus their 1-year survival rate was 33%. The new development or
      progression of graft-versus-host disease after a primed DLI was observed in 50%
      of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the
      induction of a graft-versus-leukemia effect through a primed DLI, using
      additional PBSCs reserved at the original time of harvest, would appear to be
      feasible for patients with relapsed hematologic malignancies. Furthermore, this
      approach is also more convenient for donors.

PMID- 14647259
TI  - Autologous stem cell transplantation for acute myelogenous leukemia in first
      complete remission: a 6-year follow-up study of 101 patients from a single
      institution.
AB  - The objective of the study was to assess the long-term outcome and impact of stem
      cell source in patients with acute myelogenous leukemia (AML) who received ASCT
      in first complete remission (CR). A total of 101 patients (median age 46 years)
      were included in the study. Cytogenetic categories distribution was: favorable:
      18%, intermediate: 42%, and unfavorable: 7%. More than one induction course was
      needed for CR in 21% of patients. In all, 78% of patients had received at least
      one course of high-dose ara-C before autologous stem cell transplantation (ASCT).
      Bone marrow (n=58) or peripheral blood stem cells (PBSC) (n=43) transplantation
      was performed at a median of 3.5 months from CR. Hematologic recovery and
      hospitalization duration were significantly reduced in the PBSC group. No toxic
      death was recorded in this group. The median follow-up of survivors is 67 months
      (range: 15-183). The 6-year survival, disease-free survival (DFS), and relapse
      probabilities are 44%, 38%, and 54%, respectively. The presence of a favorable
      karyotype and the use of PBSC are independently associated to better survival,
      and DFS by multivariate analysis. Our results confirm that long-term DFS can be
      achieved with high-dose chemotherapy and ASCT in patients with AML. They show
      that use of PBSC is associated to very low mortality rate and acceptable
      morbidity and contributes to an improvement of autotransplant results.

PMID- 14647260
TI  - Prolonged hypogammaglobulinemia following rituximab treatment for post transplant
      Epstein-Barr virus-associated lymphoproliferative disease.

PMID- 14647261
TI  - HistoCheck: rating of HLA class I and II mismatches by an internet-based software
      tool.
AB  - HLA polymorphism is a major barrier for hematopoietic stem cell and solid organ
      transplantation. To estimate the allogeneic potential between HLA-mismatched stem
      cell donor/recipient pairs, we recently proposed a matching score (dissimilarity
      index) that is based on the structural data of HLA class I molecules, and on the
      functional similarity of amino acids (AA). This first approach revealed new
      features about presumptive subtype allogenicities within the HLA-A*23 and A*24
      groups. We have now developed an internet-based software tool ("HistoCheck") that
      is capable to assess the allogenicity (matching score) between any pair of
      clinically relevant HLA class I, and also class II, alleles. Newly described HLA
      sequences will be regularly integrated into the database according to the
      nomenclature for factors of the HLA system updates. The software is intended to
      be a first step for estimating the allogenicity of HLA mismatches in peculiar
      clinical settings, as long as there are no reliable in vitro or clinical studies
      available. The algorithm can later be modified according to functional data, for
      example, peptide-binding specificities. With the extension of the sequence
      similarity concept to all clinically relevant HLA class I and II loci, HistoCheck
      may contribute to prevent HLA mismatching being a matter of chance.

PMID- 14647262
TI  - Inflammatory myofibroblastic tumor following hematopoietic stem cell
      transplantation: report of two pediatric cases.
AB  - Inflammatory myofibroblastic tumors are benign neoplasms histologically composed
      of lymphocytes, histiocytes, macrophages, foam cells, and plasma cells among a
      spindle-shaped stroma. Their etiology and potential for metastatic spread is
      controversial. Numerous predisposing factors have been suggested, including
      preceding infections, radiotherapy, and local trauma. We present two cases of
      pseudotumors that developed in children following hematopoietic stem cell
      transplantation. These are the first cases after hematopoietic transplant
      reported in the literature. As these neoplasms are difficult to diagnose and are
      often confused with highly aggressive tumors, our cases demonstrate that a high
      index of suspicion for such lesions must be maintained when evaluating masses in
      post transplant patients.

PMID- 14647263
TI  - Novel processes for inactivation of leukocytes to prevent transfusion-associated
      graft-versus-host disease.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious
      complication of blood component transfusion therapy. Currently, cellular blood
      components for patients recognized at risk for TA-GVHD are irradiated prior to
      transfusion in order to prevent this complication. Considerable progress has been
      made in elucidating the pathophysiology of this highly morbid complication, but
      questions as to which patients are at risk and what is the most robust technology
      to prevent TA-GVHD remain. As new technologies for inactivating or modulating
      leukocyte function are introduced, the question of how to evaluate these
      technologies becomes relevant. Over the past two decades, a number of research
      groups have explored technology to inactivate infectious pathogens and leukocytes
      contaminating cellular blood components. Few clinicians have an in-depth
      understanding of the methods or the criteria for selection of how to approach new
      technologies for leukocyte inactivation with potential to replace current
      methods. This mini review focuses on the salient aspects of current and evolving
      technology for prevention of TA-GVHD.

PMID- 14647264
TI  - A simplified approach to stem cell mobilization in multiple myeloma patients not
      previously treated with alkylating agents.
AB  - High-dose chemotherapy and autologous stem cell rescue is considered a standard
      part of initial therapy for patients with multiple myeloma. Therefore, potential
      transplant candidates are generally treated with dexamethasone-based programs
      rather than alkylating agents to avoid stem cell toxicity. The optimal mobilizing
      regimen for patients with multiple myeloma has not been defined. However,
      aggressive chemotherapy may result in excessive morbidity and cost in this older,
      immunocompromised population. We retrospectively examined our experience with a
      well-tolerated regimen of 1.5 g/m(2) cyclophosphamide on day -10 followed by 10
      microg/kg G-CSF beginning on day -7 in 50 consecutive patients with multiple
      myeloma and no prior alkylating agent therapy. Median stem cell collection was
      4.88 x 10(6) CD34+ cells/kg per apheresis and 44 patients collected >5 x 10(6)
      CD34+ cells/kg within 2 days. In 36 patients, more than 10 x 10(6) CD34+ cells/kg
      were collected including 33 patients who required 1-2 days of collection. One
      patient required hospitalization for fever/neutropenia and two required weekend
      apheresis. We conclude that 1.5 g/m(2) cyclophosphamide plus 10 microg/kg G-CSF
      is a safe, effective, highly predictable mobilizing program that uniformly
      provided enough stem cells for one transplant and enough stem cells for two
      transplants.

PMID- 14647265
TI  - More efficient mobilisation of peripheral blood stem cells with HiDAC+AMSA+G-CSF
      than with mini-ICE+G-CSF in patients with AML.
AB  - We have compared the efficacy of two PBSC mobilisation regimens, mini
      ICE+filgrastim (second consolidation) and HiDAC+AMSA+filgrastim (third
      consolidation), in two consecutive cohorts of patients with AML CR1 receiving
      treatment according to a joint protocol. Group A: 18 patients, aged 41 (21-65)
      years, were mobilised with mini-ICE (idarubicin 8 mg/m(2)+cytarabine 800
      mg/m(2)+etoposide 150 mg/m(2) days 1-3) followed by filgrastim 300-480 microg
      once daily s.c. from day 11 after start of chemotherapy. Only four patients
      reached >5 CD34+ cells/microl blood (B-CD34+) and were able to undergo
      leukaphereses. Two out of 18 (11%) reached the defined target of >/=2.0 x 10(6)
      CD34+ cells/kg after 1-3 leukaphereses. Group B: 20 patients, aged 50 (29-67)
      years, received HiDAC+AMSA (cytarabine 3 g/m(2) b.i.d. days 1, 3, 5+amsacrine 150
      mg/m(2) q.d. days 2, 4) followed by filgrastim at a similar dose starting on day
      7. A total of 18 patients reached B-CD34+ >5/microl and underwent PBSC
      harvesting, starting on day 23 (14-29) and yielding 4.0 (0.9-21) x 10(6) CD34+
      cells/kg. Of 20 patients, 17 (85%) reached the defined target of >/=2.0 x 10(6)
      CD34+ cells/kg after 1-3 leukaphereses. We conclude that HiDAC+AMSA+G-CSF - in
      contrast to mini-ICE+G-CSF - is an efficient regimen for mobilising PBSC in
      patients with AML CR1.

PMID- 14647266
TI  - Pluripotent and myeloid-committed CD34+ subsets in hematopoietic stem cell
      allografts.
AB  - The present study compared the contents of pluripotent and lineage-committed
      hematopoietic progenitor cells (HPCs) in various types of allografts. Bone marrow
      (BM) allografts and single leukapheresis products (LPs) collected from G-CSF
      mobilized donors contained similar amounts of pluripotent HPCs (CD34(+)CD38(-))
      and total CD34(+) cells. However, the content of late-myeloid HPCs
      (CD34(+)CD33(+)CD15(+)) were significantly higher in BM grafts compared to LPs
      (P>0.02), whereas the contents of early-myeloid HPCs (CD34(+)CD33(+)CD15-) were
      2.5-fold higher in LPs (P<0.03). In comparison to grafts from adult donors, cord
      blood (CB) grafts contained 26-65-fold lower amounts of early-myeloid HPCs
      (P<0.001), but only 8-12-fold lower contents of pluripotent HPCs (P<0.04).
      Additional findings demonstrated that among all tested parameters the numbers of
      early-myeloid HPCs were the most accurate measure of the total colony-forming
      cell (CFC) numbers in allografts. Hence, the earlier engraftment observed after
      transplantation of LPs compared to BM grafts might be explained by the higher
      content of early-myeloid HPCs/CFCs in LPs. Moreover, the slow engraftment
      following CB transplantation might not be affected essentially by the low number
      of myeloid HPCs, but rather by pluripotent HPCs. Finally, this study reports a
      new gating strategy for the enumeration of pluripotent CD34(+)CD38(-) subsets.

PMID- 14647267
TI  - Autologous stem cell transplantation in multiple myeloma patients <60 vs >/=60
      years of age.
AB  - The role of autologous stem cell transplantation (AuSCT) in older multiple
      myeloma patients is unclear. Using data from the Autologous Blood and Marrow
      Transplant Registry, we compared the outcome of 110 patients >/=the age of 60
      (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60
      (median 52; range 30-59) years. The two groups were similar except that older
      patients had a higher beta(2)-microglobulin level at diagnosis (P=0.016) and
      fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence
      interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in
      patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in
      patients >/=60 years. The relapse rate, progression-free survival (PFS) and
      overall survival (OS) in the two groups were also similar. Multivariate analysis
      of all patients identified only an interval from diagnosis to AuSCT >12 months
      and the use of two prior chemotherapy regimens within 6 months of AuSCT as
      adverse prognostic factors. Our results indicate that AuSCT can be safely
      performed in selected older patients: the best results were observed in patients
      undergoing AuSCT relatively early in their disease course.

PMID- 14647268
TI  - Outcome after autologous and allogeneic stem cell transplantation for patients
      with multiple myeloma: impact of graft-versus-myeloma effect.
AB  - A total of 228 patients with multiple myeloma (MM), 166 patients receiving
      autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell
      depleted allogeneic transplantation were analyzed to compare overall survival
      (OS), progression-free survival (PFS) and risk of relapse. Patients receiving
      autologous transplantation had a significantly improved OS (P=0.006) and PFS
      (P=0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%,
      respectively, compared with 51% and 28% for allogeneic transplantation. By 4
      years after transplantation, outcome was similar with OS and PFS for autologous
      transplantation 41% and 23%, respectively, compared with 39% and 18% for
      allogeneic transplantation. The 4-year cumulative incidence of nonrelapse
      mortality was significantly higher in patients receiving allogeneic
      transplantation (24% vs 13%) (P=0.004). Relapse was the principle cause of
      treatment failure for both groups; however, there was a significantly reduced
      risk of relapse associated with allogeneic transplantation at 4 years: 46% for
      allograft vs 56% for autograft (P=0.02). Despite a lower risk of relapse after
      allogeneic transplantation, autologous transplantation is associated with
      improved OS and PFS compared with allogeneic transplantation in patients with MM.
      Strategies focused on reducing nonrelapse mortality in allogeneic transplantation
      may translate into an improved outcome for patients receiving allogeneic
      transplantation.

PMID- 14647269
TI  - Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for
      primary breast cancer patients.
AB  - The incidence of secondary myelodysplasia/acute myeloid leukemia (AML) was
      retrospectively assessed in an international joint study in 305 node-positive
      breast cancer patients, who received mitoxantrone-based high-dose chemotherapy
      (HDCT) followed by autologous stem cell support as adjuvant therapy. The median
      age of the patients was 57 years (range 22-67). In all, 268 patients received
      peripheral blood stem cells, and 47 patients received autologous bone marrow.
      After a median follow-up of 57 months (range 10-125), three cases of secondary
      AML (sAML) were observed, resulting in a cumulative incidence of 0.94%. One case
      of sAML developed 18 months after HDCT (FAB M3) The karyotype was translocation
      15;17 and, after induction therapy, the patient underwent autologous stem cell
      transplantation, and is in complete remission (CR) of both breast cancer and AML.
      The second patient developed AML (FAB M4eo with inversion 16) 5 months after
      HDCT. This patient achieved CR after induction therapy, but died of infectious
      complication. A third patient developed AML (FAB M4) 6 months after HDCT. She
      achieved CR after induction therapy, but relapsed and expired 28 months after
      diagnosis of AML. sAML after mitoxantrone-based HDCT is a possible, but rare
      complication in breast cancer patients.

PMID- 14647270
TI  - Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas
      relapsed after allogeneic stem cell transplantation.
AB  - Donor lymphocyte infusions (DLI) are used to treat relapsed haematological
      diseases after allogeneic stem cell transplantation (SCT). We treated seven
      patients with DLI for indolent non-Hodgkin's lymphoma relapsed after SCT. In
      available blood and bone marrow samples, lymphoma cells were analysed by real
      time quantitative polymerase chain reaction of t(14;18)-positive cells in
      follicular lymphoma, and by immunophenotyping in small lymphocytic lymphoma.
      Before DLI, three patients were treated with chemo- and/or radiotherapy, and one
      with rituximab. Evaluable responses to pre-DLI therapy were stable disease in one
      and partial remission (PR) in two patients. Six patients responded to DLI
      (complete remission (CR) in four and PR in two). After DLI, acute graft-versus
      host disease (GVHD) occurred in 3/6 patients, classified as grade 2, whereas only
      limited chronic GVHD was seen (n=5). The four continuous CR are lasting for
      median 65+ (43-89) months. In the remaining patient, not responding to DLI,
      progressive disease was seen later on; chemotherapy followed by another DLI
      resulted in CR. In three cases, clinical responses to DLI could be substantiated
      by molecular or immunophenotypic analysis of lymphoma cells. We conclude that DLI
      is effective for treatment of indolent lymphoma relapsing after SCT.

PMID- 14647271
TI  - In vitro assessment of bone marrow endothelial colonies (CFU-En) in non-Hodgkin's
      lymphoma patients undergoing peripheral blood stem cell transplantation.
AB  - The distribution and functional characteristics of in vitro bone marrow (BM)
      endothelial colonies (CFU-En) were studied in 70 non-Hodgkin's lymphoma (NHL)
      patients in different phases of the disease to explore the association between
      CFU-En growth and angiogenesis, and between the number of CFU-En and the presence
      of hematopoietic and mesenchymal progenitor cells. The mean number of CFU
      En/10(6) BM mononuclear cells seen in remission patients was significantly higher
      than that seen in newly diagnosed patients (P=0.04), and in normal subjects
      (P=0.008). Patients with low-grade NHL in remission displayed a higher CFU-En
      value compared with high-grade NHL (P=0.04). In the autograft group (40
      patients), a significant reduction of CFU-En number was detected in the first 4-6
      months after transplantation. In remission patients, the CFU-En number positively
      correlated with the incidence of BM colony-forming unit granulocyte-macrophage
      (CFU-GM) (P=0.013) and CFU-multilineage (CFU-GEMM) hematopoietic colonies
      (P=0.044). These in vitro data show that CFU-En numbers increase following
      standard-dose chemotherapy, thus providing a rationale for further investigating
      the effects of different cytostatic drugs on BM endothelial cells growth and
      function.

PMID- 14647272
TI  - Male predominance among Japanese adult patients with late-onset hemorrhagic
      cystitis after hematopoietic stem cell transplantation.
AB  - Late-onset hemorrhagic cystitis (LHC) after hematopoietic stem cell
      transplantation (HSCT) is mainly caused by viral infections. We retrospectively
      analyzed the records of 141 Japanese adult patients who underwent a first
      allogeneic HSCT from 1995 to 2002. In all, 19 patients developed LHC a median of
      51 days after HSCT. Adenovirus (AdV) was detected in the urine of 10 LHC
      patients, of whom eight had AdV type 11. Five of the six available serum samples
      from these patients were also positive for AdV type 11, but the detection of AdV
      in serum was not associated with a worse outcome. Male sex and the development of
      grade II-IV acute graft-versus-host disease were identified as independent
      significant risk factors for LHC. Male predominance was detected in LHC after
      HSCT, as has been previously shown in children with AdV-induced acute HC. The
      detection of AdV DNA in serum did not predict a poor outcome.

PMID- 14647273
TI  - High expression of active CDK6 in the cytoplasm of CD8 memory cells favors rapid
      division.
AB  - Antigen-driven CD8 memory T cell proliferation is more rapid than that of naive T
      cells, ensuring efficient control of the pathogen after reinfection. We show here
      that naive and memory cells are in different states of G0/G1 arrest. Naive cells
      are in a classical state of G0/G1 arrest, with high expression of p27Kip1 and low
      CDK6 and CDK2 kinase activity. In contrast, memory cells have low expression of
      p27Kip1 and high CDK6 kinase activity. This preactivated kinase is associated
      with cyclin D3 in the cytoplasm, and neutralization of these complexes with
      antibody to cyclin D3 blocks the rapid division of memory cells. Therefore G0/G1
      memory cells are at a unique preactivated state that favors rapid division after
      antigen stimulation.

PMID- 14647274
TI  - Evidence from the generation of immunoglobulin G-secreting cells that stochastic
      mechanisms regulate lymphocyte differentiation.
AB  - Naive B lymphocytes undergo isotype switching and develop into immunoglobulin
      secreting cells to generate the appropriate class and amount of antibody
      necessary for effective immunity. Although this seems complex, we report here
      that the generation of immunoglobulin G-secreting cells from naive precursors is
      highly predictable. The probabilities of isotype switching and development into
      secreting cells change with successive cell divisions and interleave
      independently. Cytokines alter the probability of each differentiation event,
      while leaving intact their independent assortment. As a result, cellular
      heterogeneity arises automatically as the cells divide. Stochastic division
      linked regulation of heterogeneity challenges the conventional paradigms linking
      distinct phenotypes to unique combinations of signals and has the potential to
      simplify our concept of immune complexity considerably.

PMID- 14647275
TI  - Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile
      hemochromatosis.
AB  - Juvenile hemochromatosis is an early-onset autosomal recessive disorder of iron
      overload resulting in cardiomyopathy, diabetes and hypogonadism that presents in
      the teens and early 20s (refs. 1,2). Juvenile hemochromatosis has previously been
      linked to the centromeric region of chromosome 1q (refs. 3-6), a region that is
      incomplete in the human genome assembly. Here we report the positional cloning of
      the locus associated with juvenile hemochromatosis and the identification of a
      new gene crucial to iron metabolism. We finely mapped the recombinant interval in
      families of Greek descent and identified multiple deleterious mutations in a
      transcription unit of previously unknown function (LOC148738), now called HFE2,
      whose protein product we call hemojuvelin. Analysis of Greek, Canadian and French
      families indicated that one mutation, the amino acid substitution G320V, was
      observed in all three populations and accounted for two-thirds of the mutations
      found. HFE2 transcript expression was restricted to liver, heart and skeletal
      muscle, similar to that of hepcidin, a key protein implicated in iron metabolism.
      Urinary hepcidin levels were depressed in individuals with juvenile
      hemochromatosis, suggesting that hemojuvelin is probably not the hepcidin
      receptor. Rather, HFE2 seems to modulate hepcidin expression.

PMID- 14647277
TI  - Delivering essential function.

PMID- 14647276
TI  - Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor
      proliferation and migration in the human cerebral cortex.
AB  - Disruption of human neural precursor proliferation can give rise to a small brain
      (microcephaly), and failure of neurons to migrate properly can lead to an
      abnormal arrest of cerebral cortical neurons in proliferative zones near the
      lateral ventricles (periventricular heterotopia). Here we show that an autosomal
      recessive condition characterized by microcephaly and periventricular heterotopia
      maps to chromosome 20 and is caused by mutations in the gene ADP-ribosylation
      factor guanine nucleotide-exchange factor-2 (ARFGEF2). By northern-blot analysis,
      we found that mouse Arfgef2 mRNA levels are highest during embryonic periods of
      ongoing neuronal proliferation and migration, and by in situ hybridization, we
      found that the mRNA is widely distributed throughout the embryonic central
      nervous system (CNS). ARFGEF2 encodes the large (>200 kDa) brefeldin A (BFA)
      inhibited GEF2 protein (BIG2), which is required for vesicle and membrane
      trafficking from the trans-Golgi network (TGN). Inhibition of BIG2 by BFA, or by
      a dominant negative ARFGEF2 cDNA, decreases cell proliferation in vitro,
      suggesting a cell-autonomous regulation of neural expansion. Inhibition of BIG2
      also disturbed the intracellular localization of such molecules as E-cadherin and
      beta-catenin by preventing their transport from the Golgi apparatus to the cell
      surface. Our findings show that vesicle trafficking is an important regulator of
      proliferation and migration during human cerebral cortical development.

PMID- 14647278
TI  - GermOnline, a new cross-species community annotation database on germ-line
      development and gametogenesis.

PMID- 14647279
TI  - Chipping away at the chip bias: RNA degradation in microarray analysis.

PMID- 14647282
TI  - A RUNX trio with a taste for autoimmunity.

PMID- 14647283
TI  - The collagen-mitochondria connection.

PMID- 14647284
TI  - A molecular switch controlling renal sodium and potassium excretion.

PMID- 14647285
TI  - Free energy lights the path toward more effective RNAi.

PMID- 14647290
TI  - Altered awareness of voluntary action after damage to the parietal cortex.
AB  - A central question in the study of human behavior is the origin of willed action.
      EEG recordings of surface brain activity from human subjects performing a self
      initiated movement show that the subjective experience of wanting to move
      follows, rather than precedes, the 'readiness potential'--an electrophysiological
      mark of motor preparation. This raises the issue of how conscious experience of
      willed action is generated. Here we show that patients with parietal lesions can
      report when they started moving, but not when they first became aware of their
      intention to move. This stands in contrast with the performance of cerebellar
      patients who behaved as normal subjects. We thus propose that when a movement is
      planned, activity in the parietal cortex, as part of a cortico-cortical
      sensorimotor processing loop, generates a predictive internal model of the
      upcoming movement. This model might form the neural correlate of motor awareness.

PMID- 14647291
TI  - Attention increases neural selectivity in the human lateral occipital complex.
AB  - It is well established that attention increases the efficiency of information
      processing, but the neural mechanisms underlying this improvement are not fully
      understood. Evidence indicates that neural firing rates increase for attended
      stimuli, but another possibility is that attention could increase the selectivity
      of the neural population representing an attended stimulus. We tested this latter
      hypothesis by using functional magnetic resonance imaging (fMRI) to measure
      population selectivity for object views under different attention conditions in
      the human lateral occipital complex (LOC). Our data not only show increased
      neural activity (or 'gain') with attention, consistent with existing models, but
      also increased population selectivity that cannot be accounted for by gain
      mechanisms alone. Our results suggest that attention increases the specificity of
      the neural population representing an attended object.

PMID- 14647293
TI  - Polycomb CBX7 has a unifying role in cellular lifespan.
AB  - In contrast to cancer cells and embryonic stem cells, the lifespan of primary
      human cells is finite. After a defined number of population doublings, cells
      enter in an irreversible growth-arrested state termed replicative senescence.
      Mutations of genes involved in immortalization can contribute to cancer. In a
      genetic screen for cDNAs bypassing replicative senescence of normal human
      prostate epithelial cells (HPrEC), we identified CBX7, a gene that encodes a
      Polycomb protein, as shown by sequence homology, its interaction with Ring1 and
      its localization to nuclear Polycomb bodies. CBX7 extends the lifespan of a wide
      range of normal human cells and immortalizes mouse fibroblasts by downregulating
      expression of the Ink4a/Arf locus. CBX7 does not inter-function or colocalize
      with Bmi1, and both can exert their actions independently of each other as shown
      by reverse genetics. CBX7 expression is downregulated during replicative
      senescence and its ablation by short-hairpin RNA (shRNA) treatment inhibited
      growth of normal cells though induction of the Ink4a/Arf locus. Taken together,
      these data show that CBX7 controls cellular lifespan through regulation of both
      the p16(Ink4a)/Rb and the Arf/p53 pathways.

PMID- 14647292
TI  - Mammalian formin-1 participates in adherens junctions and polymerization of
      linear actin cables.
AB  - During epithelial sheet formation, linear actin cables assemble at nascent
      adherens junctions. This process requires alpha-catenin and actin polymerization,
      although the underlying mechanism is poorly understood. Here, we show that formin
      1 interacts with alpha-catenin, localizes to adherens junctions and nucleates
      unbranched actin filaments. Furthermore, disruption of the alpha-catenin-formin-1
      interaction blocks assembly of radial actin cables and perturbs intercellular
      adhesion. A fusion protein of the beta-catenin-binding domain of alpha-catenin
      with the actin polymerization domains of formin-1 rescues formation of adherens
      junctions and associated actin cables in alpha-catenin-null keratinocytes. These
      findings provide new insight into how alpha-catenin orchestrates actin dynamics
      during intercellular junction formation.

PMID- 14647294
TI  - Developing open access.

PMID- 14647295
TI  - The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin
      ligases?
AB  - The COP9 signalosome (CSN) is a highly conserved protein complex implicated in
      diverse biological functions that involve ubiquitin-mediated proteolysis.
      Paradoxically, conserved enzymatic activities associated with CSN inhibit cullin
      ubiquitin ligase activity in vitro, whereas mutational analysis suggests that CSN
      promotes cullin-dependent proteolysis in vivo. This apparent paradox can be
      resolved in a model that proposes CSN-mediated cullin inhibition is a
      prerequisite for the proper assembly and maintenance of active cullin ubiquitin
      ligase complexes.

PMID- 14647296
TI  - Programmed cell death: Superman meets Dr Death.
AB  - This year's Cold Spring Harbor meeting on programmed cell death (September 17-21,
      2003), organised by Craig Thompson and Junying Yuan, was proof that the 'golden
      age' of research in this field is far from over. There was a flurry of
      fascinating insights into the regulation of diverse apoptotic pathways and
      unexpected non-apoptotic roles for some of the key apoptotic regulators and
      effectors. In addition to their role in cell death, components of the apoptotic
      molecular machinery are now known to also function in a variety of essential
      cellular processes, such as regulating glucose homeostasis, lipid metabolism,
      cell proliferation and differentiation.

PMID- 14647298
TI  - Calcium orchestrates apoptosis.

PMID- 14647299
TI  - Kinesin: walking or limping?

PMID- 14647300
TI  - AP-1B: polarized sorting at the endosome.

PMID- 14647302
TI  - Go ahead, break my symmetry!

PMID- 14647305
TI  - Systemic tumor targeting and killing by Sindbis viral vectors.
AB  - Successful cancer gene therapy requires a vector that systemically and
      specifically targets tumor cells throughout the body. Although several vectors
      have been developed to express cytotoxic genes via tumor-specific promoters or to
      selectively replicate in tumor cells, most are taken up and expressed by just a
      few targeted tumor cells. By contrast, we show here that blood-borne Sindbis
      viral vectors systemically and specifically infect tumor cells. A single
      intraperitoneal treatment allows the vectors to target most tumor cells, as
      demonstrated by immunohistochemistry, without infecting normal cells. Further,
      Sindbis infection is sufficient to induce complete tumor regression. We
      demonstrate systemic vector targeting of tumors growing subcutaneously,
      intrapancreatically, intraperitoneally and in the lungs. The vectors can also
      target syngeneic and spontaneous tumors in immune-competent mice. We document the
      anti-tumor specificity of a vector that systemically targets and eradicates tumor
      cells throughout the body without adverse effects.

PMID- 14647306
TI  - Principles of transcriptional control in the metabolic network of Saccharomyces
      cerevisiae.
AB  - Cellular networks are subject to extensive regulation, which modifies the
      availability and efficiency of connections between components in response to
      external conditions. Thus far, studies of large-scale networks have focused on
      their connectivity, but have not considered how the modulation of this
      connectivity might also determine network properties. To address this issue, we
      analyzed how the coordinated expression of enzymes shapes the metabolic network
      of Saccharomyces cerevisiae. By integrating large-scale expression data with the
      structural description of the metabolic network, we systematically characterized
      the transcriptional regulation of metabolic pathways. The analysis revealed
      recurrent patterns, which may represent design principles of metabolic gene
      regulation. First, we find that transcription regulation biases metabolic flow
      toward linearity by coexpressing only distinct branches at metabolic
      branchpoints. Second, individual isozymes were often separately coregulated with
      distinct processes, providing a means of reducing crosstalk between pathways
      using a common reaction. Finally, transcriptional regulation defined a
      hierarchical organization of metabolic pathways into groups of varying expression
      coherence. These results emphasize the utility of incorporating regulatory
      information when analyzing properties of large-scale cellular networks.

PMID- 14647307
TI  - Trials, tribulations and diversification.

PMID- 14647308
TI  - Beyond belief.

PMID- 14647309
TI  - Companies jostle for access to public markets.

PMID- 14647310
TI  - Germany biotech gets second chance.

PMID- 14647311
TI  - Regulators equivocate on safety of clones.

PMID- 14647312
TI  - Biotechs await single European financial market.

PMID- 14647313
TI  - US bioethics committee weighs in.

PMID- 14647314
TI  - Europe responds to UK's GM field trials.

PMID- 14647315
TI  - EU wrangles internally over safety of donated tissues and cells.

PMID- 14647317
TI  - Ultrafast DNA sequencing.

PMID- 14647318
TI  - UK field-scale evaluations answer wrong questions.

PMID- 14647319
TI  - Vox populi and public policy: why should we care?

PMID- 14647320
TI  - Time to drop the language of 'consensus'.

PMID- 14647321
TI  - Biotechnology and the UN's Millennium Development Goals.

PMID- 14647322
TI  - Biotech IPOs: handle with care.

PMID- 14647324
TI  - Unlocking the money-making potential of RNAi.

PMID- 14647325
TI  - Fluorescent proteins with ties that bind.

PMID- 14647326
TI  - Mending the message.

PMID- 14647327
TI  - Bt-resistance management--theory meets data.

PMID- 14647328
TI  - Cloning by numbers.

PMID- 14647329
TI  - UK farm-scale evaluations of transgenic herbicide-tolerant crops.

PMID- 14647331
TI  - Approaches for the sequence-specific knockdown of mRNA.
AB  - Over the past 25 years there have been thousands of published reports describing
      applications of antisense nucleic acid derivatives for targeted inhibition of
      gene function. The major classes of antisense agents currently used by
      investigators for sequence-specific mRNA knockdowns are antisense
      oligonucleotides (ODNs), ribozymes, DNAzymes and RNA interference (RNAi).
      Whatever the method, the problems for effective application are remarkably
      similar: efficient delivery, enhanced stability, minimization of off-target
      effects and identification of sensitive sites in the target RNAs. These
      challenges have been in existence from the first attempts to use antisense
      research tools, and need to be met before any antisense molecule can become
      widely accepted as a therapeutic agent.

PMID- 14647335
TI  - The patent gamble: strategic insights for playing the worldwide patent game.

PMID- 14647339
TI  - Toward an integrated biotechnological engineering education program: a Canadian
      perspective.

PMID- 14647340
TI  - Emergence of a molecular Bose-Einstein condensate from a Fermi gas.
AB  - The realization of superfluidity in a dilute gas of fermionic atoms, analogous to
      superconductivity in metals, represents a long-standing goal of ultracold gas
      research. In such a fermionic superfluid, it should be possible to adjust the
      interaction strength and tune the system continuously between two limits: a
      Bardeen-Cooper-Schrieffer (BCS)-type superfluid (involving correlated atom pairs
      in momentum space) and a Bose-Einstein condensate (BEC), in which spatially local
      pairs of atoms are bound together. This crossover between BCS-type superfluidity
      and the BEC limit has long been of theoretical interest, motivated in part by the
      discovery of high-temperature superconductors. In atomic Fermi gas experiments
      superfluidity has not yet been demonstrated; however, long-lived molecules
      consisting of locally paired fermions have been reversibly created. Here we
      report the direct observation of a molecular Bose-Einstein condensate created
      solely by adjusting the interaction strength in an ultracold Fermi gas of atoms.
      This state of matter represents one extreme of the predicted BCS-BEC continuum.

PMID- 14647341
TI  - Facing up to endangered apes.

PMID- 14647342
TI  - Eastern promise.

PMID- 14647343
TI  - State department woos weapons researchers in bid to rebuild Iraq.

PMID- 14647344
TI  - Germany puts faith in big guns as science ministry feels pinch.

PMID- 14647345
TI  - GloFish casts light on murky policing of transgenic animals.

PMID- 14647346
TI  - Promega changes tack in battle over patent.

PMID- 14647347
TI  - US draws up plans to tackle autism.

PMID- 14647348
TI  - University buildings named on shaky ground.

PMID- 14647350
TI  - US on sidelines as China prepares for satellite launch.

PMID- 14647349
TI  - Russian claims first in magnetic imaging.

PMID- 14647353
TI  - Space science: unstoppable force.

PMID- 14647352
TI  - Fish farming: eat your veg.

PMID- 14647354
TI  - Filling the gap between knowing and doing.

PMID- 14647355
TI  - Open access: the JCI has already shown it works.

PMID- 14647356
TI  - Aircraft give a new view of jellyfish behaviour.

PMID- 14647361
TI  - Scientist: four golden lessons.

PMID- 14647362
TI  - Linguistics: trees of life and of language.

PMID- 14647363
TI  - Cell biology: thanks for the memory.

PMID- 14647364
TI  - Planetary science: conveyed to the Kuiper belt.

PMID- 14647365
TI  - Comparative genomics: two worms are better than one.

PMID- 14647367
TI  - Astronomy: beacons in the distant cosmos.

PMID- 14647368
TI  - Structural biology: dual approach to a light problem.

PMID- 14647369
TI  - Earth science: the ultraslow difference.

PMID- 14647371
TI  - Pharmacology: uncoupling the agony from ecstasy.
AB  - The recreational use of amphetamine-type stimulants can produce a marked and
      sometimes lethal increase in body temperature. Here we show that mice deficient
      in a mitochondrial protein known as UCP-3 (for 'uncoupling protein-3') have a
      diminished thermogenic response to the drug MDMA (3,4
      methylenedioxymethamphetamine, nicknamed 'ecstasy') and so are protected against
      this dangerously toxic effect. Our findings indicate that UCP-3 is important in
      MDMA-induced hyperthermia and point to a new therapeutic direction for solving an
      increasing public-health problem.

PMID- 14647372
TI  - Photonic crystals: imaging by flat lens using negative refraction.
AB  - The positive refractive index of conventional optical lenses means that they need
      curved surfaces to form an image, whereas a negative index of refraction allows a
      flat slab of a material to behave as a lens and focus electromagnetic waves to
      produce a real image. Here we demonstrate this unique feature of imaging by a
      flat lens, using the phenomenon of negative refraction in a photonic crystalline
      material. The key advance that enabled us to make this observation lies in the
      design of a photonic crystal with suitable dispersion characteristics to achieve
      negative refraction over a wide range of angles.

PMID- 14647373
TI  - An ultraslow-spreading class of ocean ridge.
AB  - New investigations of the Southwest Indian and Arctic ridges reveal an ultraslow
      spreading class of ocean ridge that is characterized by intermittent volcanism
      and a lack of transform faults. We find that the mantle beneath such ridges is
      emplaced continuously to the seafloor over large regions. The differences between
      ultraslow- and slow-spreading ridges are as great as those between slow- and fast
      spreading ridges. The ultraslow-spreading ridges usually form at full spreading
      rates less than about 12 mm yr(-1), though their characteristics are commonly
      found at rates up to approximately 20 mm yr(-1). The ultraslow-spreading ridges
      consist of linked magmatic and amagmatic accretionary ridge segments. The
      amagmatic segments are a previously unrecognized class of accretionary plate
      boundary structure and can assume any orientation, with angles relative to the
      spreading direction ranging from orthogonal to acute. These amagmatic segments
      sometimes coexist with magmatic ridge segments for millions of years to form
      stable plate boundaries, or may displace or be displaced by transforms and
      magmatic ridge segments as spreading rate, mantle thermal structure and ridge
      geometry change.

PMID- 14647374
TI  - An atypical haem in the cytochrome b(6)f complex.
AB  - Photosystems I and II (PSI and II) are reaction centres that capture light energy
      in order to drive oxygenic photosynthesis; however, they can only do so by
      interacting with the multisubunit cytochrome b(6)f complex. This complex receives
      electrons from PSII and passes them to PSI, pumping protons across the membrane
      and powering the Q-cycle. Unlike the mitochondrial and bacterial homologue
      cytochrome bc(1), cytochrome b(6)f can switch to a cyclic mode of electron
      transfer around PSI using an unknown pathway. Here we present the X-ray structure
      at 3.1 A of cytochrome b(6)f from the alga Chlamydomonas reinhardtii. The
      structure bears similarities to cytochrome bc(1) but also exhibits some unique
      features, such as binding chlorophyll, beta-carotene and an unexpected haem
      sharing a quinone site. This haem is atypical as it is covalently bound by one
      thioether linkage and has no axial amino acid ligand. This haem may be the
      missing link in oxygenic photosynthesis.

PMID- 14647375
TI  - The formation of the Kuiper belt by the outward transport of bodies during
      Neptune's migration.
AB  - The 'dynamically cold Kuiper belt' consists of objects on low-inclination orbits
      between approximately 40 and approximately 50 au from the Sun. It currently
      contains material totalling less than a tenth the mass of the Earth, which is
      surprisingly low because, according to accretion models, the objects would not
      have grown to their present size unless the cold Kuiper belt originally contained
      tens of Earth masses of solids. Although several mechanisms have been proposed to
      produce the observed mass depletion, they all have significant limitations. Here
      we show that the objects currently observed in the dynamically cold Kuiper belt
      were most probably formed within approximately 35 au and were subsequently pushed
      outward by Neptune's 1:2 mean motion resonance during its final phase of
      migration. Combining our mechanism with previous work, we conclude that the
      entire Kuiper belt formed closer to the Sun and was transported outward during
      the final stages of planet formation.

PMID- 14647376
TI  - Microfluidic sorting in an optical lattice.
AB  - The response of a microscopic dielectric object to an applied light field can
      profoundly affect its kinetic motion. A classic example of this is an optical
      trap, which can hold a particle in a tightly focused light beam. Optical fields
      can also be used to arrange, guide or deflect particles in appropriate light
      field geometries. Here we demonstrate an optical sorter for microscopic particles
      that exploits the interaction of particles-biological or otherwise-with an
      extended, interlinked, dynamically reconfigurable, three-dimensional optical
      lattice. The strength of this interaction with the lattice sites depends on the
      optical polarizability of the particles, giving tunable selection criteria. We
      demonstrate both sorting by size (of protein microcapsule drug delivery agents)
      and sorting by refractive index (of other colloidal particle streams). The
      sorting efficiency of this method approaches 100%, with values of 96% or more
      observed even for concentrated solutions with throughputs exceeding those
      reported for fluorescence-activated cell sorting. This powerful, non-invasive
      technique is suited to sorting and fractionation within integrated ('lab-on-a
      chip') microfluidic systems, and can be applied in colloidal, molecular and
      biological research.

PMID- 14647377
TI  - Low-temperature processing of 'baroplastics' by pressure-induced flow.
AB  - The manufacturing of plastics traditionally involves melt processing at
      temperatures typically greater than 200 degrees C-to enable extrusion or moulding
      under pressure into desired forms-followed by solidification. This process
      consumes energy and can cause substantial degradation of polymers and additives
      (such as flame retardants and ultraviolet stabilizers), limiting plastics
      performance and recyclability. It was recently reported that the application of
      pressure could induce melt-like behaviour in the block copolymer polystyrene
      block-poly(n-butyl methacrylate) (PS-b-PBMA), and this behaviour has now been
      demonstrated in a range of other block copolymer systems. These polymers have
      been termed baroplastics. However, in each case, the order-to-disorder
      transition, which gives rise to the accompanying change in rheology from soft
      solid to melt, was observed at temperatures far exceeding the glass transition
      temperatures (T(g)) of both components. Here we show that baroplastic systems
      containing nanophase domains of one high-T(g) and one low-T(g) component can
      exhibit melt-like flow under pressure at ambient temperature through an apparent
      semi-solid partial mixing mechanism that substantially preserves the high-T(g)
      phase. These systems were shredded and remoulded ten times with no evident
      property degradation. Baroplastics with low-temperature formability promise lower
      energy consumption in manufacture and processing, reduced use of additives,
      faster production and improved recyclability, and also provide potential
      alternatives to current thermoplastic elastomers, rubber-modified plastics, and
      semi-crystalline polymers.

PMID- 14647378
TI  - Synthetic design of crystalline inorganic chalcogenides exhibiting fast-ion
      conductivity.
AB  - Natural porous solids such as zeolites are invariably formed with inorganic
      cations such as Na(+) and K(+) (refs 1, 2). However, current research on new
      porous materials is mainly focused on the use of organic species as either
      structure-directing or structure-building units; purely inorganic systems have
      received relatively little attention in exploratory synthetic work. Here we
      report the synthesis of a series of three-dimensional sulphides and selenides
      containing highly mobile alkali metal cations as charge-balancing extra-framework
      cations. Such crystalline inorganic chalcogenides integrate zeolite-like
      architecture with high anionic framework polarizability and high concentrations
      of mobile cations. Such structural features are particularly desirable for the
      development of fast-ion conductors. These materials demonstrate high ionic
      conductivity (up to 1.8 x 10(-2) ohm(-1) cm(-1)) at room temperature and moderate
      to high humidity. This synthetic methodology, together with novel structural,
      physical and chemical properties, may lead to the development of new microporous
      and open-framework materials with potential applications in areas such as
      batteries, fuel cells, electrochemical sensors and photocatalysis.

PMID- 14647379
TI  - Explosive volcanism may not be an inevitable consequence of magma fragmentation.
AB  - The fragmentation of magma, containing abundant gas bubbles, is thought to be the
      defining characteristic of explosive eruptions. When viscous stresses associated
      with the growth of bubbles and the flow of the ascending magma exceed the
      strength of the melt, the magma breaks into disconnected fragments suspended
      within an expanding gas phase. Although repeated effusive and explosive eruptions
      for individual volcanoes are common, the dynamics governing the transition
      between explosive and effusive eruptions remain unclear. Magmas for both types of
      eruptions originate from sources with similar volatile content, yet effusive
      lavas erupt considerably more degassed than their explosive counterparts. One
      mechanism for degassing during magma ascent, consistent with observations, is the
      generation of intermittent permeable fracture networks generated by non-explosive
      fragmentation near the conduit walls. Here we show that such fragmentation can
      occur by viscous shear in both effusive and explosive eruptions. Moreover, we
      suggest that such fragmentation may be important for magma degassing and the
      inhibition of explosive behaviour. This implies that, contrary to conventional
      views, explosive volcanism is not an inevitable consequence of magma
      fragmentation.

PMID- 14647380
TI  - Language-tree divergence times support the Anatolian theory of Indo-European
      origin.
AB  - Languages, like genes, provide vital clues about human history. The origin of the
      Indo-European language family is "the most intensively studied, yet still most
      recalcitrant, problem of historical linguistics". Numerous genetic studies of
      Indo-European origins have also produced inconclusive results. Here we analyse
      linguistic data using computational methods derived from evolutionary biology. We
      test two theories of Indo-European origin: the 'Kurgan expansion' and the
      'Anatolian farming' hypotheses. The Kurgan theory centres on possible
      archaeological evidence for an expansion into Europe and the Near East by Kurgan
      horsemen beginning in the sixth millennium BP. In contrast, the Anatolian theory
      claims that Indo-European languages expanded with the spread of agriculture from
      Anatolia around 8,000-9,500 years bp. In striking agreement with the Anatolian
      hypothesis, our analysis of a matrix of 87 languages with 2,449 lexical items
      produced an estimated age range for the initial Indo-European divergence of
      between 7,800 and 9,800 years bp. These results were robust to changes in coding
      procedures, calibration points, rooting of the trees and priors in the bayesian
      analysis.

PMID- 14647381
TI  - Contributions of microbial biofilms to ecosystem processes in stream mesocosms.
AB  - In many aquatic ecosystems, most microbes live in matrix-enclosed biofilms and
      contribute substantially to energy flow and nutrient cycling. Little is known,
      however, about the coupling of structure and dynamics of these biofilms to
      ecosystem function. Here we show that microbial biofilms changed the physical and
      chemical microhabitat and contributed to ecosystem processes in 30-m-long stream
      mesocosms. Biofilm growth increased hydrodynamic transient storage-streamwater
      detained in quiescent zones, which is a major physical template for ecological
      processes in streams-by 300% and the retention of suspended particles by 120%. In
      addition, by enhancing the relative uptake of organic molecules of lower
      bioavailability, the interplay of biofilm microarchitecture and mass transfer
      changed their downstream linkage. As living zones of transient storage, biofilms
      bring hydrodynamic retention and biochemical processing into close spatial
      proximity and influence biogeochemical processes and patterns in streams. Thus,
      biofilms are highly efficient and successful ecological communities that may also
      contribute to the influence that headwater streams have on rivers, estuaries and
      even oceans through longitudinal linkages of local biogeochemical and
      hydrodynamic processes.

PMID- 14647382
TI  - Balanced inhibition underlies tuning and sharpens spike timing in auditory
      cortex.
AB  - Neurons in the primary auditory cortex are tuned to the intensity and specific
      frequencies of sounds, but the synaptic mechanisms underlying this tuning remain
      uncertain. Inhibition seems to have a functional role in the formation of
      cortical receptive fields, because stimuli often suppress similar or neighbouring
      responses, and pharmacological blockade of inhibition broadens tuning curves.
      Here we use whole-cell recordings in vivo to disentangle the roles of excitatory
      and inhibitory activity in the tone-evoked responses of single neurons in the
      auditory cortex. The excitatory and inhibitory receptive fields cover almost
      exactly the same areas, in contrast to the predictions of classical lateral
      inhibition models. Thus, although inhibition is typically as strong as
      excitation, it is not necessary to establish tuning, even in the receptive field
      surround. However, inhibition and excitation occurred in a precise and
      stereotyped temporal sequence: an initial barrage of excitatory input was rapidly
      quenched by inhibition, truncating the spiking response within a few (1-4)
      milliseconds. Balanced inhibition might thus serve to increase the temporal
      precision and thereby reduce the randomness of cortical operation, rather than to
      increase noise as has been proposed previously.

PMID- 14647383
TI  - An ancient role for nuclear beta-catenin in the evolution of axial polarity and
      germ layer segregation.
AB  - The human oncogene beta-catenin is a bifunctional protein with critical roles in
      both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta
      catenin signalling has been implicated in developmental processes as diverse as
      elaboration of embryonic polarity, formation of germ layers, neural patterning,
      spindle orientation and gap junction communication, but the ancestral function of
      beta-catenin remains unclear. In many animal embryos, activation of beta-catenin
      signalling occurs in blastomeres that mark the site of gastrulation and
      endomesoderm formation, raising the possibility that asymmetric activation of
      beta-catenin signalling specified embryonic polarity and segregated germ layers
      in the common ancestor of bilaterally symmetrical animals. To test whether
      nuclear translocation of beta-catenin is involved in axial identity and/or germ
      layer formation in 'pre-bilaterians', we examined the in vivo distribution,
      stability and function of beta-catenin protein in embryos of the sea anemone
      Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta
      catenin is differentially stabilized along the oral-aboral axis, translocated
      into nuclei in cells at the site of gastrulation and used to specify entoderm,
      indicating an evolutionarily ancient role for this protein in early pattern
      formation.

PMID- 14647384
TI  - Angiotensin-converting enzyme 2 is a functional receptor for the SARS
      coronavirus.
AB  - Spike (S) proteins of coronaviruses, including the coronavirus that causes severe
      acute respiratory syndrome (SARS), associate with cellular receptors to mediate
      infection of their target cells. Here we identify a metallopeptidase, angiotensin
      converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive
      Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We
      found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked
      association of the S1 domain with Vero E6 cells. 293T cells transfected with
      ACE2, but not those transfected with human immunodeficiency virus-1 receptors,
      formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS
      CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T
      cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on
      Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for
      SARS-CoV.

PMID- 14647385
TI  - Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes
      autoimmune arthritis in mice.
AB  - Rheumatoid arthritis (RA), which afflicts about 1% of the world population, is a
      chronic systemic inflammatory disease of unknown aetiology that primarily affects
      the synovial membranes of multiple joints. Although CD4(+) T cells seem to be the
      prime mediators of RA, it remains unclear how arthritogenic CD4(+) T cells are
      generated and activated. Given that highly self-reactive T-cell clones are
      deleted during normal T-cell development in the thymus, abnormality in T-cell
      selection has been suspected as one cause of autoimmune disease. Here we show
      that a spontaneous point mutation of the gene encoding an SH2 domain of ZAP-70, a
      key signal transduction molecule in T cells, causes chronic autoimmune arthritis
      in mice that resembles human RA in many aspects. Altered signal transduction from
      T-cell antigen receptor through the aberrant ZAP-70 changes the thresholds of T
      cells to thymic selection, leading to the positive selection of otherwise
      negatively selected autoimmune T cells. Thymic production of arthritogenic T
      cells due to a genetically determined selection shift of the T-cell repertoire
      towards high self-reactivity might also be crucial to the development of disease
      in a subset of patients with RA.

PMID- 14647386
TI  - A positive-feedback-based bistable 'memory module' that governs a cell fate
      decision.
AB  - The maturation of Xenopus oocytes can be thought of as a process of cell fate
      induction, with the immature oocyte representing the default fate and the mature
      oocyte representing the induced fate. Crucial mediators of Xenopus oocyte
      maturation, including the p42 mitogen-activated protein kinase (MAPK) and the
      cell-division cycle protein kinase Cdc2, are known to be organized into positive
      feedback loops. In principle, such positive feedback loops could produce an
      actively maintained 'memory' of a transient inductive stimulus and could explain
      the irreversibility of maturation. Here we show that the p42 MAPK and Cdc2 system
      normally generates an irreversible biochemical response from a transient
      stimulus, but the response becomes transient when positive feedback is blocked.
      Our results explain how a group of intrinsically reversible signal transducers
      can generate an irreversible response at a systems level, and show how a cell
      fate can be maintained by a self-sustaining pattern of protein kinase activation.

PMID- 14647387
TI  - Specific cytotoxic T cells eliminate cells producing neutralizing antibodies.

PMID- 14647390
TI  - Small world, big hopes.

PMID- 14647391
TI  - Polymorphisms within 5' end of the Neuregulin 1 gene are genetically associated
      with schizophrenia in the Chinese population.

PMID- 14647394
TI  - Monoamine depletion in psychiatric and healthy populations: review.
AB  - A number of techniques temporarily lower the functioning of monoamines: acute
      tryptophan depletion (ATD), alpha-methyl-para-tyrosine (AMPT) and acute
      phenylalanine/tyrosine depletion (APTD). This paper reviews the results of
      monoamine depletion studies in humans for the period 1966 until December 2002.
      The evidence suggests that all three interventions are specific, in terms of
      their short-term effects on one or two neurotransmitter systems, rather than on
      brain protein metabolism in general. The AMPT procedure is somewhat less
      specific, affecting both the dopamine and norepinephrine systems. The behavioral
      effects of ATD and AMPT are remarkably similar. Neither procedure has an
      immediate effect on the symptoms of depressed patients; however, both induce
      transient depressive symptoms in some remitted depressed patients. The magnitude
      of the effects, response rate and quality of response are also comparable. APTD
      has not been studied in recovered major depressive patients. Despite the
      similarities, the effects are distinctive in that ATD affects a subgroup of
      recently remitted patients treated with serotonergic medications, whereas AMPT
      affects recently remitted patients treated with noradrenergic medications. The
      evidence also suggests that ATD and APTD affect different cognitive functions, in
      particular different memory systems. Few studies investigated cognitive effects
      of the procedures in patients. Patients who are in remission for longer may also
      be vulnerable to ATD and AMPT, but the relationship with prior treatment is much
      weaker. For these patients, individual vulnerability markers are the more
      important determinants of depressive response, making these techniques
      potentially useful models of vulnerability to depression.

PMID- 14647395
TI  - Differential effects of learning on neurogenesis: learning increases or decreases
      the number of newly born cells depending on their birth date.
AB  - The hippocampal formation, to which new neurons are added on a daily basis
      throughout life, is important in spatial learning. Surviving de novo produced
      cells integrate into the functional circuitry, where they can influence both
      normal and pathological behaviors. In this study, we examined the effect of the
      water-maze (a hippocampal-dependent spatial task) on neurogenesis. Learning in
      this task can be divided into two phases, an early phase during which performance
      improves rapidly, and a late phase during which asymptotic levels of performance
      are reached. Here we demonstrate that the late phase of learning has a
      multifaceted effect on neurogenesis depending on the birth date of new neurons.
      The number of newly born cells increased contingently with the late phase and a
      large proportion of these cells survived for at least 4 weeks and differentiated
      into neurons. In contrast, late-phase learning decreased the number of newly born
      cells produced during the early phase. This decline in neurogenesis was
      positively correlated with performance in the water-maze. Thus, rats with the
      highest de novo cell number were less able to acquire and use spatial information
      than those with low numbers of new cells. These results show that learning has a
      complex effect on hippocampal neurogenesis, and reveals a novel mechanism through
      which neurogenesis may influence normal and pathological behaviors.

PMID- 14647396
TI  - Antipsychotic drug treatment alters expression of mRNAs encoding lipid metabolism
      related proteins.
AB  - Using an automated PCR-based genomics approach, TOtal Gene expression Analysis
      (TOGA), we have examined gene expression profiles of mouse striatum and frontal
      cortex in response to clozapine and haloperidol drug treatment. Of 17 315 mRNAs
      observed, TOGA identified several groups of related molecules that were regulated
      by drug treatment. The expression of some genes encoding proteins involved in
      neurotransmission, signal transduction, oxidative stress, cell adhesion,
      apoptosis and proteolysis were altered in the brains of both clozapine- and
      haloperidol-treated mice as recognized by TOGA. Most notable was the differential
      expression of those genes whose products are associated with lipid metabolism.
      These include apolipoprotein D (apoD), the mouse homolog of oxysterol-binding
      protein-like protein 8 (OSBPL8), a diacylglycerol receptor (n-chimerin), and
      lysophosphatidic acid (LPA) acyltransferase. Real-time PCR analysis confirmed
      increases in the RNA expression of apoD (1.6-2.2-fold) and OSBPL8 (1.7-2.6-fold),
      and decreases in the RNA expression of n-chimerin (1.5-2.2-fold) and LPA
      acyltransferase (1.5-fold) in response to haloperidol and/or clozapine treatment.
      Additional molecules related to calcium homeostasis and signal transduction, as
      well as four sequences of previously unidentified mRNAs, were also confirmed by
      real-time PCR to be regulated by drug treatment. While antipsychotic drugs may
      affect several metabolic pathways, lipid metabolism/signaling pathways may be of
      particular importance in the mechanisms of antipsychotic drug action and in the
      pathophysiology of psychiatric disorders.

PMID- 14647397
TI  - Antidepressants are functional antagonists at the serotonin type 3 (5-HT3)
      receptor.
AB  - Antidepressants are commonly supposed to enhance serotonergic and/or
      noradrenergic neurotransmission by inhibition of neurotransmitter reuptake
      through binding to the respective neurotransmitter transporters or through
      inhibition of the monoamine oxidase. Using the concentration-clamp technique and
      measurements of intracellular Ca2+, we demonstrate that different classes of
      antidepressants act as functional antagonists at the human 5-HT3A receptor stably
      expressed in HEK 293 cells and at endogenous 5-HT3 receptors of rat hippocampal
      neurons and N1E-115 neuroblastoma cells. The tricyclic antidepressants
      desipramine, imipramine, and trimipramine, the serotonin reuptake inhibitor
      fluoxetine, the norepinephrine reuptake inhibitor reboxetine, and the
      noradrenergic and specific serotonergic antidepressant mirtazapine effectively
      reduced the serotonin-induced Na(+)- and Ca(2)(+)-currents in a dose-dependent
      fashion. This effect was voltage-independent and, with the exception of
      mirtazapine, noncompetitive. Desipramine, imipramine, trimipramine, and
      fluoxetine also accelerated receptor desensitization. Moclobemide and
      carbamazepine had no effect on the serotonin-induced cation current. By analyzing
      analogues of desipramine and carbamazepine, we found that a basic propylamine
      side chain increases the antagonistic potency of tricyclic compounds, whereas it
      is abolished by an uncharged carboxamide group. The antagonistic effects of
      antidepressants at the 5-HT3 receptor did not correlate with their effects on
      membrane fluidity. In conclusion, structurally different types of antidepressants
      modulate the function of this ligand-gated ion channel. This may represent a yet
      unrecognized pharmacological principle of antidepressants.

PMID- 14647399
TI  - mRNA expression of apoptosis-associated genes in infant acute lymphoblastic
      leukemia: low Fas expression is an independent predictor for poor prognosis.

PMID- 14647400
TI  - Amplification of RNA transcripts using terminal continuation.
AB  - A new methodology has been developed to amplify RNA from minute amounts of
      starting material. Specifically, an efficient means of second-strand (ss) cDNA
      synthesis using a sequence-specific 'terminal continuation' (TC) method is
      demonstrated. An RNA synthesis promoter is attached to the 3' and/or 5' region of
      cDNA utilizing the TC mechanism. The orientation of amplified RNAs is 'antisense'
      or a novel 'sense' orientation. TC RNA amplification is utilized for many
      downstream applications including gene expression profiling, cDNA microarray
      analysis, and cDNA library/subtraction library construction. Synthesized sense TC
      amplified RNA can also be used as a template for in vitro protein translations
      and downstream proteomic applications. The TC RNA amplification methodology
      offers high sensitivity, flexibility, and throughput capabilities. A likely
      mechanism is that the TC primer binds preferentially to GC-rich CpG islands
      flanking 5' regions of DNA that contain promoter sequences. Following TC RNA
      amplification, a large proportion of genes can be assessed quantitatively as
      evidenced by bioanalysis and cDNA microarray analysis in mouse and human
      postmortem brain tissues.

PMID- 14647401
TI  - Examination of MCP-1 (CCL2) partitioning and presentation during transendothelial
      leukocyte migration.
AB  - It is proposed that a chemokine concentration gradient promotes vectorial
      leukocyte migration across the vascular endothelium during inflammation. In this
      study, monocyte migration across a model endothelial monolayer was assessed at
      defined time-points after the addition of MCP-1 (CCL2). At each time-point
      transendothelial migration was quantified, medium from the apical and basal
      surface was collected for ELISA and monolayers were stained to detect both
      heparan sulfate and MCP-1. Statistically significant monocyte migration was
      observed within 60 min of chemokine addition to the basal surface of the
      endothelium and an asymmetric distribution of MCP-1 across the monolayer was
      observed at all time-points. Dual color immunofluorescence analysis demonstrated
      that MCP-1 was focused into heparan sulfate-containing domains on the apical
      surface of some of the endothelial cells. Furthermore, no uniform concentration
      gradient of chemokine was observed within the space between adjacent endothelial
      cells with apical MCP-1 application resulting in a staining pattern identical to
      that observed after basal application. The addition of a functional, monomeric
      form of MCP-1 produced a staining pattern identical to that observed using the
      wild-type protein, suggesting that localized chemokine oligomerization is not
      responsible for generating the focal chemokine distribution. Together, these data
      suggest that apical presentation of concentrated, chemokine-containing domains
      provides sufficient stimulus to promote transendothelial leukocyte migration in
      the absence of the formation of a formal haptotactic concentration gradient
      between endothelial cells.

PMID- 14647402
TI  - Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and
      function in organ fibrogenesis.
AB  - Cytoglobin/stellate cell activation-associated protein (Cygb/STAP) consists of a
      new class of hexacoordinate globin superfamily, which was recently discovered by
      a proteome analysis on the rat hepatic stellate cells. Unlike haemoglobin,
      myoglobin, and neuroglobin, Cygb/STAP is ubiquitously expressed in several
      organs, although its detailed localization has not been clarified.
      Immunohistochemistry and immunoelectron microscopy revealed that Cygb/STAP is
      uniquely localized in fibroblast-like cells in splanchnic organs, namely the
      vitamin A-storing cell lineage, but neither in epithelial cells, endothelial
      cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. The
      expression of Cygb/STAP was upregulated in fibrotic lesions of the pancreas and
      kidney in which activated fibroblast-like cells or myofibroblasts are known to
      increase in number. In cultured hepatic stellate cells, Cygb/STAP expression was
      augmented by the stimulation with sera, platelet-derived growth factor-BB, and
      transforming growth factor-beta 1. Overexpression of Cygb/STAP in NIH 3T3 cells
      induced the cells to lessen migratory activities and increase the expression of
      collagen alpha1(I) mRNA. These results indicate that Cygb/STAP is a tissue globin
      uniquely localized in splanchnic fibroblastic cell lineage and may play a role in
      fibrotic organ disorder.

PMID- 14647403
TI  - Evaluation of the carcinogenic effects of furazolidone and its metabolites in two
      fish species.
AB  - The major metabolite from the use of furazolidone (FZD) in mammals, birds and
      fish is 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1alpha, 2-di(2-oxo-oxazolidin
      3-yl)iminomethyl-furo[2,3-beta]furan, also called 3-amine-2-oxazolidone (AOZ). A
      minor metabolite was identified as N-(5-amine-2-furfuryliden)-3-amine-2
      oxazolidone (FOZ). To assess the potential carcinogenicity of FZD and the
      metabolic mixture of AOZ/FOZ, 11 mg FZD/kg feed/day was fed for 12 weeks to
      mollies (Poecilia formosa), an ornamental fish species prone to develop tumors.
      The rate of tumors was quantified and defined both in mollies and their
      offspring. Then, some fish was made into fishmeal and incorporated into fish food
      at 500 g of meal/kg of food and fed to other mollies for 12 weeks. The rate of
      tumors was assessed. A similar trial design was carried out in tilapia fish
      (Oreochromis niloticus) by adding 50 mg FZD/kg to the feed for 90 days. All
      animals were placed in glass fishponds under controlled laboratory conditions.
      Each week, a significant biomass was collected from both groups to assess the
      macroscopic and histopathological changes. All mollies developed
      melanohistiocytomic tumors in the liver and other organs. Offspring from
      surviving mollie females stimulated to breed showed no changes compared to
      control animals. None of the mollies fed with the mollie-meal food contaminated
      with AOZ/FOZ developed tumors. Neither tilapia medicated with FZD nor tilapia fed
      with tilapia-meal contaminated with AOZ/FOZ developed tumors. These results do
      not support the established viewpoint that FZD must be banned from trophic chains
      based on its potential carcinogenic properties.

PMID- 14647404
TI  - Association between a G-protein beta 3 subunit gene polymorphism and the
      symptomatology and treatment responses of major depressive disorders.
AB  - The genes involved in signal transduction are major candidates in association
      studies on affective disorders and responses to antidepressants. We investigated
      whether the C825T polymorphism of the beta3 subunit of G protein (GNB3) gene is
      associated with the symptom severity or treatment response of major depressive
      disorders (MDDs) in a Korean sample of 106 MDD patients; our study also included
      133 healthy controls. Hypertensive subjects were excluded from the study because
      association between GNB3 variants and hypertension has been reported in previous
      studies. We found significantly more carriers of the 825T allele in MDD patients
      than in normal controls (chi(2)=6.37, P=0.012; OR=2.19, 95% CI 1.18-4.05). The T
      allele carriers showed higher scores than those with the CC genotype in the
      baseline total and in some subcategories of the Hamilton Depression Rating Scale
      (P<0.05). We also found a statistically significant association between T-allele
      carriers and antidepressant treatment response (P<0.05). These results suggest
      that the T allele of the C825T polymorphism in the GNB3 gene is associated with
      MDD. It was also demonstrated that MDD patients bearing the T allele had a severe
      symptomatology and a better response to antidepressant treatment than patients
      without the T allele.

PMID- 14647405
TI  - CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers.
AB  - CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The
      CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A
      mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and
      CYP3A5 in vitro. The aim of this study was to elucidate the influence of the
      CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule
      containing 10 mg of nifedipine was administered to 16 healthy male Japanese
      subjects (eight subjects: CYP3A5(*)1/(*)3; eight subjects: CYP3A5(*)3/(*)3).
      Blood samples were collected to analyze the pharmacokinetics of serum nifedipine
      and nitropyridine metabolite (M-I). The area under the plasma concentration-time
      curve (AUC), the peak plasma concentration (C(max)) and the terminal half-life
      (t(1/2)) of nifedipine, and the ratio of the nifedipine AUC to M-I AUC showed
      large intragroup variations, but no significant differences between the two
      genotypes. Based on the present findings, the functional relevance of CYP3A5
      polymorphism should be re-evaluated in clinical trials.

PMID- 14647406
TI  - Protecting communities in pharmacogenetic and pharmacogenomic research.
AB  - The existing EELS literature has usefully identified the scope of ethical issues
      posed by pharmacogenetic and pharmacogenomic research. The time has come for in
      depth examination of particular ethical issues. The involvement of racial and
      ethnic communities in pharmacogenetic and pharmacogenomic research is contentious
      precisely because it touches upon the science and politics of studying racial and
      ethnic difference. To date, the ethics literature has not seriously taken account
      of the fact that such research impinges upon the interests of communities, and
      that taking such interests seriously requires that we both protect and empower
      communities in research. We propose a framework that rests upon the recognition
      that communities are heterogeneous human associations and differing policies are
      appropriate for differing communities. Community consent and consultation and
      community consultation alone are neither appropriate nor required for all
      pharmacogenetic and pharmacogenomic research. Rather, application of these policy
      protections must take into account particulars of both planned research and the
      communities involved.

PMID- 14647407
TI  - A Gilbert's syndrome UGT1A1 variant confers susceptibility to tranilast-induced
      hyperbilirubinemia.
AB  - Tranilast (N-(3'4'-demethoxycinnamoyl)-anthranilic acid (N-5)) is an
      investigational drug for the prevention of restenosis following percutaneous
      transluminal coronary revascularization. An increase in bilirubin levels was
      observed in 12% of patients upon administration of tranilast in a phase III
      clinical trial. To identify the potential genetic factors that may account for
      the drug-induced hyperbilirubinemia, we examined polymorphisms in the uridine
      diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene in over a thousand
      patients. Our results suggested that the TA repeat polymorphism in UGT1A1, which
      predisposes some individuals to Gilbert's syndrome, predicted the susceptibility
      to tranilast-induced hyperbilirubinemia. The (TA)(7)/(TA)(7) genotype was present
      in 39% of the 127 hyperbilirubinemic patients vs 7% of the 909 controls (P=2 x
      10(-22)). Rapid identification of genetic factors accounting for the observed
      adverse effect during the course of a double-blind clinical trial demonstrated
      the potential application of pharmacogenetics in the clinical development of safe
      and effective medicines.

PMID- 14647408
TI  - Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute
      lymphoblastic leukemia.
AB  - The central role of 5,10-methylenetetrahydrofolate reductase (MTHFR) and
      methylenetetrahydrofolate dehydrogenase (MTHFD1) in folate metabolism renders
      polymorphisms in genes encoding these enzymes potential modulators of therapeutic
      response to antifolate chemotherapeutics. The analysis of 201 children treated
      with methotrexate for childhood acute lymphoblastic leukemia (ALL) showed that
      patients with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 variant had a
      lower probability of event-free survival (EFS) in univariate analysis (hazard
      ratio (HR)=2.2, 95% confidence interval (CI), 1.0-4.7 and 2.8, 95% CI, 1.1-7.3,
      respectively). Multivariate analysis supported only the role of the MTHFR variant
      (HR=2.2, 95% CI, 0.9-5.6). However, the association of both genes with ALL
      outcome appears to be more obvious in the presence of another event-predisposing
      variant belonging to the same path of drug action. The combined effect of a
      thymidylate synthase (TS) triple repeat associated with increased TS levels, with
      either the MTHFR T677A1298 haplotype or MTHFD1 A1958 allele, resulted in a highly
      significant reduction of EFS (multivariate HR=9.0, 95% CI, 1.9-42.8 and 8.9, 95%
      CI, 1.8-44.6, respectively). These results reveal the role of gene-gene
      interactions within a folate pathway, and how they can correlate with relapse
      probabilities in ALL patients.

PMID- 14647409
TI  - Discovery of Ca2+-relevant and differentiation-associated genes downregulated in
      esophageal squamous cell carcinoma using cDNA microarray.
AB  - To identify genes that are differentially expressed in human esophageal squamous
      cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176
      clones to analyse gene expression profiles in ESCC. A total of 77 genes
      (including 31 novel genes) were downregulated, and 15 genes (including one novel
      gene) were upregulated in cancer tissues compared with their normal counterparts.
      Immunohistochemistry and Northern blot analysis were carried out to verify the
      cDNA microarray results. It was revealed that genes involved in squamous cell
      differentiation were coordinately downregulated, including annexin I, small
      proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9),
      transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like
      factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes
      encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope
      (CE). Moreover, genes associated with invasion or proliferation were upregulated,
      including genes such as fibronectin, secreted protein acidic and rich in cystein
      (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the
      expression of GKLF suggested that GKLF might be able to regulate the expression
      of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the
      role of squamous cell differentiation-associated genes in ESCC initiation and
      progression.

PMID- 14647410
TI  - Tumor-derived C-terminal mutations of Smad4 with decreased DNA binding activity
      and enhanced intramolecular interaction.
AB  - Smad4 is a critical component in transforming growth factor beta (TGF-beta)
      signaling and frequently mutated in pancreatic and colorectal cancers. Smad4 has
      two important functional domains, MH1 and MH2, that are involved in different
      biological processes. The MH1 domain comprises a DNA binding domain and the MH2
      domain is mainly implicated in transcriptional activation and homo- and
      heteromeric complex formation among Smad proteins. In the present study, a total
      of nine Smad4 mutations at both MH1 and MH2 domains were analysed and all of them
      had a reduced activity to stimulate transcription of a TGF-beta-responsive
      reporter gene. All four MH1 mutations had a markedly reduced ability to bind a
      consensus Smad binding element by an in vitro assay using GST fusion proteins.
      Among the MH2 mutations, R497H, K507Q, and R515G mutations of Smad4 gave rise to
      a reduced DNA binding capacity. The R497H mutation had a slightly reduced
      interaction with Smad2 upon activation of TGF-beta receptor. However, the K507Q
      and R515G mutations greatly lost their ability to associate with Smad2. Using a
      GST pull-down assay, it was found that the Smad4 MH2 domain bearing R497H and
      R515G mutations had an enhanced interaction with the MH1 region of the Smad4
      protein, indicating that an increased intramolecular interaction by these
      mutations may alleviate the DNA binding activity at the MH1 domain. Consistent
      with these observations, the MH2 domain with R497H mutation had an enhanced
      ability to inhibit TGF-beta receptor-mediated transcription. In addition, the
      full-length R497H mutation was able to antagonize TGF-beta signaling in a
      dominant-negative manner. Therefore, these studies revealed novel mechanisms by
      which the Smad4 mutations utilize to abrogate their functions in transducing the
      signaling of TGF-beta, which plays an important role in various stages of cancer
      formation.

PMID- 14647411
TI  - Distinct roles for p53, p27Kip1, and p21Cip1 during tumor development.
AB  - Mutations in p53 and reduced expression of the Cdk inhibitor p27Kip1 are
      frequently observed in a wide variety of human cancers, but it is not known
      whether alterations in these tumor suppressors interact to influence tumor
      progression. To address this, we measured tumor latency and spectrum in p53 and
      p27 single and compound mutant mice. p53-/- (null) mice developed T-cell
      lymphomas and soft-tissue sarcomas, while p27-/- mice developed adenomas of the
      pituitary and lung, but with much longer latency. The latency for tumor
      development in p53-/- p27-/- and p53-/- p27+/- compound mutant mice was
      significantly reduced, by 15-30%, compared to single mutant p53-/- mice. The
      tumor spectrum in the compound mutants was similar to that of p53-/- mice, and
      additional tumors of diverse histotypes. In tumors from p53-/- mice, p27 protein
      levels were reduced to a greater extent than were mRNA levels, indicating that
      p27 is downregulated in tumors at the transcriptional as well as post
      transcriptional levels. In contrast, mice deficient in another Cdk inhibitor
      p21Cip1, which is also a transcriptional target and effector of p53, showed only
      a marginal increase in tumor predisposition in response to ENU treatment. Thus,
      downregulation of p27 is a common feature in p53-/- tumors. Germline deletion of
      one or both alleles of p27 accelerates tumor development and associated mortality
      in p53-/- mice, indicating potent synergy between loss of p27 and p53. Although
      p21 is functionally similar to both p53 and p27, it plays a lesser role in tumor
      suppression. These results further highlight the highly cooperative nature of p27
      and its central role in tumor suppression.

PMID- 14647412
TI  - Divergent C-terminal transactivation domains of Rel/NF-kappa B proteins are
      critical determinants of their oncogenic potential in lymphocytes.
AB  - rel/nf-kappaB genes are amplified, overexpressed, or constitutively activated in
      many human hematopoietic tumors; however, the molecular mechanisms by which they
      contribute to tumorigenesis remain to be determined. Here, we explored the
      oncogenic potential of cellular Rel/NF-kappaB proteins in vitro and in vivo. We
      show that overexpression of wild-type mouse and human c-rel genes suffices to
      malignantly transform primary spleen cells in stringent soft agar assays and
      produce fatal tumors in vivo. In contrast relA and a constitutively active form
      of IKKbeta did not. Importantly, a hybrid RelA protein with its C-terminal
      transactivation domain substituted by that of v-Rel was potently oncogenic in
      vitro and in vivo. The transactivation domain of v-Rel selectively conferred an
      oncogenic phenotype upon the Rel homology domain (RHD) of RelA, but not to the
      more divergent RHDs of p50/NF-kappaB1, p52/NF-kappaB2, or RelB. Collectively, our
      results highlight important differences in the intrinsic oncogenic activity of
      mammalian c-Rel and RelA proteins, and indicate that critical determinants of
      their differential oncogenicity reside in their divergent transactivation
      domains. These findings provide experimental evidence for a role of mammalian
      Rel/NF-kappaB factors in leukemia/lymphomagenesis in an in vivo animal model, and
      are consistent with the implication of c-rel in many human lymphomas.

PMID- 14647413
TI  - Phosphorylation of BRCA2 by the Polo-like kinase Plk1 is regulated by DNA damage
      and mitotic progression.
AB  - The breast cancer susceptibility protein, BRCA2, preserves chromosomal stability
      through roles in the repair of DNA double-strand breaks, and possibly, cell
      division. Post-translational modifications that may coordinate these functions
      remain poorly characterized. Here, we report that BRCA2 is a substrate for the
      mitotic Polo-like kinase, Plk1. BRCA2 undergoes phosphorylation in cells
      synchronously passing through the G2/M phases of cell cycle, when Plk1 expression
      and activity are maximal. Depletion of Plk1 by RNA interference suppresses BRCA2
      modification. BRCA2 and Plk1 interact with one another in cell lysates, through a
      conserved region in BRCA2, which spans the eight BRC repeat motifs essential for
      its function in DNA repair. Within this region, residues positioned between BRC
      repeats--but not the repeat motifs themselves--are phosphorylated by Plk1.
      Interestingly, Plk1-mediated modification of BRCA2 during the G2/M phases is
      inhibited by treatment with the radiomimetic agent, adriamycin. Thus, our
      findings define a regulatory circuit for BRCA2 phosphorylation by Plk1 that is
      responsive to DNA damage as well as mitotic progression.

PMID- 14647414
TI  - Molecular profiling of mouse lung tumors: association with tumor progression,
      lung development, and human lung adenocarcinomas.
AB  - We have performed oligonucleotide array analysis on various murine lung tissues
      [normal lungs, lung adenomas, and lung adenocarcinomas (ACs)] using Affymetrix
      U74Av2 GeneChips to examine the complex genetic changes occurring during lung
      carcinogenesis. Analysis yielded 20 novel genes differentially expressed in both
      lung adenomas and ACs versus normal lungs, including the tumor suppressor APC2
      and the oncogene Ros 1. In addition, 50 genes were found to be differentially
      expressed in lung adenomas versus lung ACs, including the differentiation factor
      Hox C6, the oncogene Ets 2, and the Ras nuclear transport factor, nuclear
      transport factor 2. To understand the potential relationship between genes
      expressed in murine lung tumors and its relationship to altered gene expression
      observed during embryogenesis and postnatal development, tissues from embryonic
      lungs and from lungs of mice up to 4 weeks following birth were examined using
      Affymetrix U74Av2 GeneChips. From this analysis, approximately 1300 genes were
      determined to exhibit differential expression in fetal lung versus postnatal
      lung. When we compared lung adenomas, lung ACs, and normal lung parenchyma, 24
      developmentally regulated genes were found aberrantly expressed in lung tumors;
      these included the cell cycle control factor CDC5, the cellular differentiation
      factor TEA domain 4, and the proapoptotic factor BNIP 2. Finally, we compared the
      murine lung tumor gene expression data to the expression of genes in human lung
      cancer, in order to assess the relevance of murine lung cancer models in the
      study of human AC formation. When the 17 human lung ACs and six human lung large
      cell carcinomas were examined, it was found that 13 of the 17 human lung ACs
      clustered tightly together in a pattern that was different from the remaining
      four human lung ACs and six large cell carcinomas, which exhibited a different
      pattern. Interestingly, the mouse lung adenomas appeared similar to 13 clustered
      ACs, while mouse lung ACs appeared more similar in pattern to the group
      consisting of four ACs and six large-cell carcinomas (LCCs). Nevertheless, when
      compared with the combined human ACs, 39 genes with similar expression changes in
      murine lung tumors and human ACs/LCCs were identified, such as the oncogene
      related BCL7B, the cell cycle regulator CDK4, and the proapoptotic Endophilin B1.
      Overall, we have determined, for the first time, the expression profiles during
      murine lung tumor progression and have established, at the molecular level, an
      association between murine lung tumorigenesis and lung development. We have also
      attempted to compare the expression profiles found in mouse lung cancers and
      those in human lung ACs.

PMID- 14647415
TI  - EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression
      of RhoB antagonizes oncogene-mediated transformation.
AB  - While some low molecular weight GTPases such as Ras and RhoA contribute to
      malignant transformation, a closely related family member, RhoB, has tumor
      suppressive activity, but little is known about its regulation by oncogenes. In
      this study, we show that H-Ras, N-Ras, K-Ras, EGFR and ErbB2 but not v-Src
      suppress RhoB promoter transcriptional activity in NIH3T3 cells and human cancer
      cell lines derived from lung (A-549), pancreatic (Panc-1) and cervical (C33A)
      tumors. The EGFR and ErbB2 suppression of RhoB promoter activity is mediated by
      Ras. Furthermore, Ras suppresses basal as well as 5-fluorouracil (5-FU)-induced
      RhoB promoter activity and RhoB protein levels. Ectopic expression of RhoB, but
      not the closely related family member RhoA, antagonizes the ability of EGFR,
      ErbB2, H-Ras, N-Ras and K-Ras but not v-Src to transform NIH3T3 cells.
      Furthermore, RhoB, but not RhoA, inhibits colony formation and proliferation and
      induces anoikis in A-549 cells and Ras-transformed NIH3T3 cells. Finally, Ras
      mediated resistance to 5-FU-induced apoptosis is reversed by RhoB. These results
      demonstrate that RhoB expression is negatively regulated by oncogenes that are
      prevalent in human cancers, and that ectopic expression of RhoB antagonizes the
      ability of these oncogenes to induce transformation. Taken together the data
      suggest that certain oncogenes suppress RhoB as one of the critical steps leading
      to malignant transformation.

PMID- 14647416
TI  - Human prolactin and its antagonist, hPRL-G129R, regulate bax and bcl-2 gene
      expression in human breast cancer cells and transgenic mice.
AB  - To gain insight into the molecular mechanisms involved in human prolactin
      receptor antagonist (hPRL-G129R)-induced apoptosis, we used real-time reverse
      transcription-polymerase chain reaction to measure bax and bcl-2 gene expression
      in 11 human breast cancer cell lines following treatment with hPRL and hPRL
      G129R. We also measured bax and bcl-2 gene expression in the mammary glands of
      transgenic mice expressing hPRL or hPRL-G129R. A time-course study of hPRL and
      antagonist treatment in T-47D cells indicated changing bax/bcl-2 mRNA ratios
      beginning at 24 h. We found that bax/bcl-2 mRNA ratios were significantly
      elevated in seven of the 11 hPRL-G129R-treated cell lines, as well as in the hPRL
      G129R transgenic mice. To confirm these results, Bax and Bcl-2 proteins were
      analysed by Western blot methods in mammary gland tissue homogenates of
      transgenic mice. Bax/Bcl-2 ratios were highest in the 6-month group of hPRL-G129R
      transgenics, and lowest in the 6-month group of hPRL transgenics. We expanded our
      findings by examining the release of a downstream Bax-induced protein, cytochrome
      c, a hallmark protein of apoptosis, in transgenic mice. Again, cytochrome c
      levels were highest in the 6-month hPRL-G129R transgenic group. Thus, hPRL-G129R
      induced breast cancer cell and/or mammary gland apoptosis is mediated, at least
      in part, through the regulation of Bax and Bcl-2 gene expression.

PMID- 14647417
TI  - Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell
      growth and tumorigenicity in human hepatocellular carcinoma cells.
AB  - The gene deleted in liver cancer-1 (DLC-1) is located on human chromosome 8p21
      22, a region thought to harbor tumor suppressor genes on the basis of its
      frequent deletion or loss of heterozygosity in a variety of human cancers,
      including hepatocellular carcinoma (HCC). Deletion or altered expression of DLC-1
      is common in HCC. In the current study, the subcellular localization of Dlc-1
      protein was determined by immunostaining with antibody to DLC-1 and the possible
      tumor growth suppressor activity of DLC-1 was investigated by examining the
      effects of of DLC-1 cDNA transfection in two human HCC cell lines lacking
      expression of the endogenous gene. The results show that Dlc-1protein is
      localized in the cell cytoplasm, and the restoration of DLC-1 expression in HCC
      cells resulted in caspase-3-mediated apoptosis, inhibition of cell growth and
      invasiveness in vitro as well as in reduction of the ability of the cells to form
      tumors in athymic nude mice. These observations thus support the notion that Dlc
      1 protein is involved in hepatocarcinogenesis and has oncosuppressive activity in
      HCC.

PMID- 14647418
TI  - Induction of apoptosis in human leukemia cells by the tyrosine kinase inhibitor
      adaphostin proceeds through a RAF-1/MEK/ERK- and AKT-dependent process.
AB  - Effects of the tyrphostin tyrosine kinase inhibitor adaphostin (NSC 680410) have
      been examined in human leukemia cells (Jurkat, U937) in relation to mitochondrial
      events, apoptosis, and perturbations in signaling and cell cycle regulatory
      events. Exposure of cells to adaphostin concentrations > or =0.75 microM for
      intervals > or =6 h resulted in a pronounced release of cytochrome c and AIF,
      activation of caspase-9, -8, and -3, and apoptosis. These events were accompanied
      by the caspase-independent downregulation of Raf-1, inactivation of MEK1/2, ERK,
      Akt, p70S6K, dephosphorylation of GSK-3, and activation of c-Jun-N-terminal
      kinase (JNK) and p38 MAPK. Adaphostin also induced cleavage and dephosphorylation
      of pRb on CDK2- and CDK4-specific sites, as well as the caspase-dependent
      downregulation of cyclin D1. Inducible expression of a constitutively active MEK1
      construct markedly diminished adaphostin-induced cytochrome c and AIF release,
      JNK activation, and apoptosis in Jurkat cells. Ectopic expression of Raf-1 or
      constitutively activated (myristolated) Akt also significantly attenuated
      adaphostin-induced apoptosis, but protection was less than that conferred by
      enforced activation of MEK. Lastly, antioxidants (e.g., L-N-acetylcysteine; L
      NAC) opposed adaphostin-mediated mitochondrial dysfunction, Raf-1/MEK/ERK
      downregulation, JNK activation, and apoptosis. However, in contrast to L-NAC,
      enforced activation of MEK failed to block adaphostin-mediated ROS generation.
      Together, these findings demonstrate that the tyrphostin adaphostin induces
      multiple perturbations in signal transduction pathways in human leukemia cells,
      particularly inactivation of the cytoprotective Raf-1/MEK/ERK and Akt cascades,
      that culminate in mitochondrial injury, caspase activation, and apoptosis. They
      also suggest that adaphostin-related oxidative stress acts upstream of
      perturbations in these signaling pathways to trigger the cell death process.

PMID- 14647419
TI  - Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers:
      implications for treatment and survival.
AB  - Inactivation of the FANC-BRCA pathway via promoter methylation of the FANCF gene
      renders cells sensitive to DNA crosslinking agents, and has been identified in
      ovarian cancer cell lines and sporadic primary tumor tissues. We investigated
      epigenetic alterations in the FANC-BRCA pathway in head and neck squamous cell
      carcinomas (HNSCC) and non-small-cell lung cancers (NSCLC) using methylation
      specific PCR. Promoter methylation of FANCF occurred in 15% (13/89) of HNSCCs and
      14% (22/158) of NSCLCs. Methylation of BRCA1 occurred only in 6/158 NSCLC, and
      was limited to adenocarcinomas and large-cell carcinomas of the lung. No
      methylation of BRCA2 was detected. FANCF methylation was associated with a
      shorter duration of tobacco use (P=0.03) and a younger age of starting smoking
      (P=0.06) in NSCLC, and with a greater number of years of alcohol drinking
      (P=0.02) in HNSCC. In adenocarcinomas of the lung, FANCF promoter methylation was
      a significant predictor of poor survival with a hazard ratio of 3.1 (95% CI 1.2
      7.9). This study demonstrates that inactivation of the FANC-BRCA pathway is
      relatively common in solid tumors and may be related to tobacco and alcohol
      exposure and survival of these patients.

PMID- 14647420
TI  - Loss of the Smad3 expression increases susceptibility to tumorigenicity in human
      gastric cancer.
AB  - Loss of the tumor suppressive effect of transforming growth factor-beta (TGF
      beta) has been commonly found at later stages in carcinogenic progression.
      Although the genes encoding TGF-beta receptors and Smads have been found
      genetically altered in certain human cancers, no mutation in Smad3 has been
      observed. Therefore, suppression of Smad3 expression may mediate key oncogenic
      properties of TGF-beta. First, we observed that 37.5% of human gastric cancer
      tissues showed low to undetectable levels of Smad3 and that in nine human gastric
      cancer cell lines examined, two showed deficient Smad3 expression. Introduction
      of Smad3 into human gastric cancer cells that did not express Smad3, restored TGF
      beta responsiveness: induction of p21 and p15 gene expression, and growth
      inhibition in response to TGF-beta. Furthermore, these Smad3-expressing cells
      showed markedly decreased and delayed tumorigenicity in vivo. These findings
      suggest that Smad3 expression may have a critical role in tumor suppression in
      the early stages of gastric carcinogenesis.

PMID- 14647421
TI  - Density-dependent location and interactions of truncated APC and beta-catenin.
AB  - Adenomatous polyposis coli (APC) is a multifunctional tumour suppressor protein,
      central to development and the mature organism. It is mutated in most cases of
      colorectal cancer, rendering it ineffective in mediating beta-catenin
      degradation. We show that localization of full-length APC in colon carcinoma and
      noncancer cell lines is independent of cell density. However, the location of
      truncated APC is a function of cell density and in high-density cells truncated
      APC is predominantly not nuclear. Although the distribution of truncated APC and
      beta-catenin is closely linked in subconfluent SW480 cells, at high cell density
      they are not colocalized. We postulated that in this cell line this could be due
      to an increase in beta-catenin bound to E-cadherin with formation of adherens
      junctions at high cell density. However, while in coimmunoprecipitation assays we
      observe an increase in binding between beta-catenin and E-cadherin and a
      corresponding decrease in binding between beta-catenin and APC at high cell
      density, we did not observe a strict colocalization of beta-catenin and E
      cadherin at the membrane of all cells.

PMID- 14647422
TI  - IFNalpha induces Fas expression and apoptosis in hedgehog pathway activated BCC
      cells through inhibiting Ras-Erk signaling.
AB  - Basal cell carcinoma (BCC), the most common form of human cancer, is understood
      to be associated with activation of the sonic hedgehog pathway, through loss-of
      function mutations of tumor suppressor PTCH1 or gain-of-function mutations of
      smoothened. Interferon (IFN)-based therapy is quite effective in BCC treatment,
      but the molecular basis is not well understood. Here we report a novel mechanism
      by which IFNalpha mediates apoptosis in BCCs. In the presence of IFNalpha, we
      observed increased apoptosis in a BCC cell line ASZ001, in which PTC is null, and
      therefore with constitutive activation of the sonic hedgehog pathway. We
      demonstrate that SMO agonist Ag-1.4 mediates activation of extracellular signal
      regulated kinase (Erk) phosphorylation, which is abrogated by IFNalpha in sonic
      hedgehog responsive C3H10T1/2 cells. In transient transfection experiments, we
      demonstrate that IFNalpha inhibits Erk phosphorylation and serum response element
      activation induced by expression of SMO, Gli1, PDGFRalpha and activated Raf, but
      not activated mitogen-activated Erk-regulating kinase (Mek), suggesting that
      IFNalpha targets mainly on Mek function. We further show that IFNalpha induces
      expression of Fas in BCC cells through interfering with Mek function. The role of
      the Fas-L/Fas signaling axis in IFNalpha-mediated apoptosis is demonstrated by
      the fact that addition of Fas-L neutralizing antibodies, just as caspase-8
      inhibitor Z-IETD-FMK, effectively prevents IFNalpha-mediated apoptosis. Thus, our
      data indicate that IFNalpha-based BCC therapy induces Fas expression and
      apoptosis through interfering with Mek function.

PMID- 14647423
TI  - Multiple G-protein-coupled receptor signals converge on the epidermal growth
      factor receptor to promote migration and invasion.
AB  - Signalling through G-protein-coupled receptors (GPCRs) and receptor tyrosine
      kinases (RTK) is involved in the regulation of essential cellular processes and
      its deregulation is associated with tumorigenesis in vitro and in vivo. We
      investigated pathophysiological processes that are regulated by GPCR pathways in
      human kidney and bladder cancer cell lines. Our results show that GPCR ligands
      induce tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as
      well as downstream signalling events such as recruitment of the adapter protein
      Shc and activation of the mitogen-activated protein kinases (MAPK) ERK1/2, JNK
      and p38. Moreover, we report that the EGFR transactivation signal involves the
      EGFR ligands amphiregulin, HB-EGF and TGFalpha as well as the metalloproteinases
      ADAM 10, 15 and 17, depending on the cellular system. Finally, we demonstrate
      that EGFR transactivation is part of a regulatory system that modulates the
      migratory and invasive behaviour of kidney and bladder cancer cells. In
      conclusion, our findings demonstrate that metalloproteinase-mediated
      transactivation of the EGFR is a key mechanism of the cellular signalling network
      that promotes MAPK activation as well as tumour cell migration and invasion in
      response to a variety of physiologically relevant GPCR ligands, and therefore
      represents a novel target for cancer intervention strategies.

PMID- 14647424
TI  - Additive effect of p53, p21 and Rb deletion in triple knockout primary
      hepatocytes.
AB  - Using Cre-Lox technology to inducibly delete Rb from wild-type, p21- and/or p53
      deficient primary hepatocytes, we investigated the role of p53, p21 and pRb in
      the regulation of liver cell proliferation, polyploidization and death. These
      cellular decisions are critical to maintaining liver cell replacement in disease,
      and in determining the likelihood of carcinogenesis in chronic liver injury.
      Clearly, the present study shows a complex interplay between p53, p21 and pRb,
      which regulates the likelihood of hepatocytes stimulated from quiescence, to
      proliferate, undergo polyploidy or die. It reveals that these proteins act both
      in concert and independently, demonstrating that a small set of key cellular
      players is common to diverse cell decisions of fundamental importance to disease.

PMID- 14647425
TI  - Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec
      protein tyrosine kinase.
AB  - The Dok adaptor family of proteins binding to RasGAP, consisting of Dok-1 and Dok
      2, are critical regulators in cell proliferation. These molecules are partners
      and/or substrates of different protein tyrosine kinases considered as
      oncoproteins. Here, we show that Dok-1 and Dok-2 are the major tyrosine
      phosphorylated proteins associated to Tec, a protein tyrosine kinase expressed in
      T cells. Furthermore, we evaluate the effect of Dok-1 or Dok-2 on Tec-mediated
      signalling pathways in T cells. Here, we provide evidence that Dok-1 and Dok-2
      proteins are involved in a negative feedback regulation of Tec via a
      downregulation of its tyrosine phosphorylation and downstream signalling pathways
      including the Ras pathway. Either Dok-1 or Dok-2 therefore represents a mean of
      potent retrograde control for protein tyrosine kinase signalling, and then
      possibly of tumor development.

PMID- 14647426
TI  - A comprehensive assessment of p53-responsive genes following adenoviral-p53 gene
      transfer in Bcl-2-expressing prostate cancer cells.
AB  - The p53 protein can induce cell cycle arrest or apoptosis following activation in
      response to DNA damage. The function of p53 is largely mediated by regulating the
      expression of downstream target genes. Adenoviral-p53 gene transfer (Ad-p53) is
      currently being evaluated in clinical trials as a therapeutic intervention. Tumor
      response is likely to be influenced by context-dependent variables, such as
      expression of bcl-2. Bcl-2 is upregulated in a variety of neoplasms, and can
      inhibit p53-dependent apoptosis. It was therefore of interest to use a global
      genomic strategy to assess gene expression following Ad-p53 gene transfer and to
      determine if the expression of specific Ad-p53-responsive genes could be
      modulated in the context of bcl-2 gene deregulation. cDNA arrays were used to
      identify p53-responsive genes following Ad-p53 gene transfer in control and bcl-2
      overexpressing PC3 prostate cancer cells. A total of 40 transcripts were
      significantly upregulated by Ad-p53 in both control and bcl-2-transfectant PC3
      cells. Conversely, 19 transcripts were significantly repressed in both cell
      lines. These Ad-p53-responsive transcripts included previously identified p53
      targets, known genes representing candidate p53 targets, and transcripts
      identified as expressed sequence tags. A subset of 15 transcripts was
      differentially modulated by Ad-p53 in the context of bcl-2. Some of these genes
      were also differentially modulated in LNCaP (wt p53) cells following DNA damage.
      These results document a number of potential p53 targets and mediators of
      therapeutically relevant genotoxic stress. The findings further suggest that bcl
      2 may inhibit cell death at multiple points downstream of p53 activation.

PMID- 14647427
TI  - Effect of haemopoietic growth factors on cancer cell lines and their role in
      chemosensitivity.
AB  - The recombinant growth factors (GFs) erythropoietin (Epo) and granulocyte
      macrophage colony stimulating factor (GM-CSF) have important roles in the
      management of cancer patients. However, the effects of these GFs at a cellular
      level are not well understood. We examined the effect of GFs alone, and in
      combination with cytotoxic chemotherapy, in a panel of seven cell lines. Flow
      cytometric analysis showed varying levels of receptor expression, which
      correlated with phosphorylated MAPK expression. Additionally, there were also
      concomitant increases in BCL-2 protein levels in those cells with high levels of
      MAPK activation. Although culturing cells with Epo or GM-CSF did not alter cell
      viability by themselves, GF pretreatment in cell lines expressing higher receptor
      levels resulted in a reduced magnitude of cell kill following exposure to
      cytotoxic IC50 concentrations of cisplatin. Subsequent co-culture with either the
      MEK inhibitor U0126 or the GM-CSF antagonist E21R negated this induced resistance
      to cytotoxic chemotherapy, confirming the importance of the GF receptor as well
      as MAPK in mediating these effects. These results suggest that the use of GFs
      during chemotherapy may be detrimental in those cancers expressing higher levels
      of the specific receptor. Conversely, our results also suggest that GFs are safe
      to use in chemotherapeutic regimens if the cancer cells do not overexpress the
      particular receptor.

PMID- 14647428
TI  - Differential protein synthesis and expression levels in normal and neoplastic
      human prostate cells and their regulation by type I and II interferons.
AB  - Protein expression and de novo synthesis in normal and prostate cancer cell lines
      derived from the same patient were compared by proteomic analysis, and the
      effects of INFalpha and INFgamma (INF=interferon) determined. The expressions of
      several INF-inducible proteins, including MxA, Nmi, PA28a and IFP53, were
      downregulated in the cancer cells. INFgamma induced a more than twofold increase
      or decrease in the synthesis rates of almost twice as many proteins in the cancer
      cell line. The positive regulator of INF-induced transcription ISGF3gamma was
      upregulated in the cancer cells and inversely regulated by INFalpha and INFgamma
      in the normal and cancer cells. Moreover, ISGF3gamma's induction by INFgamma in
      the cancer cells was more enhanced by simultaneous stimulation with EGF, than its
      induction in the normal cells. In all, 31 differentially regulated proteins were
      identified by mass spectrometry analysis, several of which are involved in
      chaperone-assisted protein folding in the endoplasmic reticulum (ER) or in
      regulated protein degradation. Our results suggest that the exclusion of proteins
      by the ER quality control system, crosstalk between the EGF- and INF-induced
      signalling pathways and the regulation of INF-inducible genes are all altered in
      the prostate cancer cells. The combination of upregulated activity in the growth
      promoting PI3K/Akt pathway, suppression of Nmi and overexpression of hnRNP-K and
      c-myc proteins may explain why the prostate cancer cells were found to be more
      resistant to the growth inhibitory effects of INFgamma.

PMID- 14647429
TI  - Gadd45a regulates matrix metalloproteinases by suppressing DeltaNp63alpha and
      beta-catenin via p38 MAP kinase and APC complex activation.
AB  - The p53-regulated growth arrest and DNA damage-inducible gene product Gadd45a has
      been recently identified as a key factor protecting the epidermis against
      ultraviolet radiation (UVR)-induced skin tumors by activating p53 via the stress
      mitogen-activated protein kinase (MAPK) signaling pathway. Herein we identify
      Gadd45a as an important negative regulator of two oncogenes commonly over
      expressed in epithelial tumors: the p53 homologue DeltaNp63alpha and beta
      catenin. DeltaNp63alpha is one of the several p63 isoforms and is the predominant
      species expressed in basal epidermal keratinocytes. DeltaNp63alpha lacks the N
      terminal transactivation domain and behaves as a dominant-negative factor
      blocking expression of several p53-effector genes. DeltaNp63alpha also associates
      with and blocks activation of the adenomatous polyposis coli (APC) destruction
      complex that targets free cytoplasmic beta-catenin for degradation. While most
      beta-catenin protein is localized to the cell membrane and is involved in cell
      cell adhesion, accumulation of free cytoplasmic beta-catenin will translocate
      into the nucleus where it functions in a bipartite transcription factor complex,
      whose targets include invasion and metastasis promoting endopeptidases, matrix
      metalloproteinases (MMP). We show that Gadd45a not only directly associates with
      two components of the APC complex, namely protein phosphatase 2A (PP2A) and
      glycogen synthase kinase 3beta (GSK3beta) but also promotes GSK3beta
      dephosphorylation at Ser9, which is essential for GSK3beta activation, and
      resultant activation of the APC destruction complex. We demonstrate that lack of
      Gadd45a not only prevents DeltaNp63alpha suppression and GSK3beta
      dephosphorylation but also prevents free cytoplasmic beta-catenin degradation
      after UV irradiation. The inability of Gadd45a-null keratinocytes to suppress
      beta-catenin may contribute to the resulting observation of increased MMP
      expression and activity along with significantly faster keratinocyte migration in
      Matrigel in vitro and accelerated wound closure in vivo. Furthermore, epidermal
      keratinocytes treated with p38 MAPK inhibitors, both in vivo and in vitro, behave
      very similarly to Gadd45a-null keratinocytes after UVR. Similarly, Trp53-null
      mice are unable to attenuate DeltaNp63alpha expression in epidermal keratinocytes
      after such stress. These findings demonstrate a dependence on Gadd45a-mediated
      p38 MAPK and p53 activation for proper modulation of DeltaNp63alpha, GSK3beta,
      and beta-catenin after irradiation. Taken together, our results indicate that
      Gadd45a is able to repress DeltaNp63alpha, beta-catenin, and consequently MMP
      expression by two means: by maintaining UVR-induced p38 MAPK and p53 activation
      and also by associating with the APC complex. This implicates Gadd45a in the
      negative regulation of cell migration, and invasion.

PMID- 14647430
TI  - Nuclear-cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity
      and is regulated by dimerization with BRCA1.
AB  - The breast cancer-associated protein, BARD1, colocalizes with BRCA1 in nuclear
      foci in the S phase and after DNA damage, and the two proteins form a stable
      heterodimer implicated in DNA repair, protein ubiquitination, and control of mRNA
      processing. BARD1 has a BRCA1-independent proapoptotic activity; however, little
      is known about its regulation. Here, we show that BARD1 localization and
      apoptotic activity are regulated by nuclear-cytoplasmic shuttling. We identified
      a functional CRM1-dependent nuclear export sequence (NES) near the N-terminal
      RING domain of BARD1. The NES forms part of the BRCA1 dimerization domain, and
      coexpression of BRCA1 resulted in masking of the NES and nuclear retention of
      BARD1. In transient expression assays, BARD1 apoptotic activity was stimulated by
      nuclear export, and both apoptotic function and nuclear export were markedly
      reduced by BRCA1. Similar findings were obtained for endogenous BARD1. Silencing
      BRCA1 expression by siRNA, or disrupting the endogenous BARD1/BRCA1 interaction
      by peptide competition caused a reduction in BARD1 nuclear localization and foci
      formation, and increased the level of cytoplasmic BARD1 correlating with
      increased apoptosis. Our findings suggest that BRCA1/BARD1 heterodimer formation
      is important for optimal nuclear targeting of BARD1 and its role in DNA repair
      and cell survival.

PMID- 14647431
TI  - A TP53 polymorphism is associated with increased risk of colorectal cancer and
      with reduced levels of TP53 mRNA.
AB  - We undertook a case-control study to examine the possible associations of the
      TP53 variants Arg > Pro at codon 72 and p53PIN3, a 16 bp insertion/duplication in
      intron 3, with the risk of colorectal cancer (CRC). The p53PIN3 A2 allele (16 bp
      duplication) was associated with an increased risk (OR 1.55, 95% CI 1.10-2.18, P
      = 0.012), of the same order of magnitude as that observed in previous studies for
      other types of cancer. The Pro72 allele was weakly associated with CRC (OR =
      1.34, 95% CI 0.98-1.84, P = 0.066). The possible functional role of p53PIN3 was
      investigated by examining the TP53 mRNA transcripts in 15 lymphoblastoid cell
      lines with different genotypes. The possibility that the insertion/deletion could
      lead to alternatively spliced mRNAs was excluded. However, we found reduced
      levels of TP53 mRNA associated with the A2 allele. In conclusion, the
      epidemiological study suggests a role for p53PIN3 in tumorigenesis, supported by
      the in vitro characterization of this variant.

PMID- 14647433
TI  - Enhanced expression of MYCN leads to centrosome hyperamplification after DNA
      damage in neuroblastoma cells.
AB  - Centrosomes play important roles in cell polarity, regulation of cell cycle and
      chromosomal stability. Centrosome abnormality is frequently found in many cancers
      and contributes to chromosomal instability (including aneuploidy, tetraploidy,
      and/or micronuclei) in daughter cells through the assembly of multipolar or
      monopolar spindles during mitosis. It has recently been reported that loss of
      tumor suppressor genes or overexpression of oncogenes causes centrosome
      hyperamplification. Amplification and overexpression of the MYCN oncogene is
      found in a subgroup of neuroblastomas. In this study, we examined whether
      overexpression of MYCN causes centrosome hyperamplification in neuroblastoma
      cells. We show that ectopic expression of MYCN alone in a neuroblastoma cell line
      did not cause centrosome hyperamplification. However, centrosome
      hyperamplification and micronuclei formation were seen in these cells after DNA
      damage. These findings suggest that overexpression of MYCN abrogates the
      regulation of the centrosome cycle after DNA damage.

PMID- 14647432
TI  - Enhanced malignant tumorigenesis in Cdk4 transgenic mice.
AB  - In a previous study, we reported that overexpression of cyclin-dependent kinase-4
      (CDK4) in mouse epidermis results in epidermal hyperplasia, hypertrophy and
      severe dermal fibrosis. In this study, we have investigated the susceptibility to
      skin tumor formation by forced expression of CDK4. Skin tumors from transgenic
      mice showed a dramatic increase in the rate of malignant progression to squamous
      cell carcinomas (SCC) in an initiation-promotion protocol. Histopathological
      analysis of papillomas from transgenic mice showed an elevated number of
      premalignant lesions characterized by dysplasia and marked atypia. Interestingly,
      transgenic mice also developed tumors in initiated but not promoted skin,
      demonstrating that CDK4 replaced the action of tumor promoters. These results
      suggest that expression of cyclin D1 upon ras activation synergizes with CDK4
      overexpression. However, cyclin D1 transgenic mice and double transgenic mice for
      cyclin D1 and CDK4 did not show increased malignant progression in comparison to
      CDK4 transgenic mice. Biochemical analysis of tumors showed that CDK4 sequesters
      the CDK2 inhibitors p27Kip1 and p21Cip1, suggesting that indirect activation of
      CDK2 plays an important role in tumor development. These results indicate that,
      contrary to the general assumption, the catalytic subunit, CDK4, has higher
      oncogenic activity than cyclin D1, revealing a potential use of CDK4 as
      therapeutic target.

PMID- 14647434
TI  - Association of Vimentin overexpression and hepatocellular carcinoma metastasis.
AB  - The poor prognosis of hepatocellular carcinoma (HCC) has been associated with
      recurrence and metastasis. Recently, we established a pair of HCC cell lines from
      a primary (H2-P) and its matched metastatic (H2-M) HCC tumors. A high density of
      cDNA microarray with 9184 human cDNA was used to identify the differentially
      expressed genes between H2-P and H2-M. Comparing with H2-P, eight upregulated and
      six downregulated genes were detected in H2-M. One interesting finding is the
      overexpression of Vimentin (VIM), a well-defined intermediate filament, which has
      been linked to a more aggressive status in various tumors. The correlation of
      overexpression of VIM and HCC metastasis was studied by immunohistochemistry
      using a tissue microarray with 200 primary HCCs and 60 pairs of primary and
      matched metastatic HCC samples. Tissue microarray demonstrated that the
      overexpression of VIM was significantly associated with HCC metastasis (P<0.01).
      This finding strongly suggests that the overexpression of VIM may play an
      important role in the metastasis of HCC.

PMID- 14647436
TI  - Characterization of functional elements in the neurofibromatosis (NF1) proximal
      promoter region.
AB  - An essential requirement to understand how genes contribute to genetic disease is
      the thorough knowledge of the transcriptional regulation of gene expression.
      Here, we have characterized transcription factor binding sites within the type 1
      neurofibromatosis (NF1) proximal regulatory region, and addressed the molecular
      mechanisms that regulate NF1 transcription. Overlapping regions of the NF1
      proximal promoter have been cloned and characterized for use in luciferase
      reporter assays. These assays have identified a 500 bp region displaying
      activities up to 80-fold higher than control reporter levels. Mutations at
      putative CRE and SP1-binding sites immediately 5' to the transcription start site
      have dramatic effects that lead to a 70-90% decrease in reporter activity in all
      cell lines tested. Gelshift assays confirm binding of CREB and SP1/KLF family
      members to their putative recognition sequences, and provide the first evidence
      identifying functional sites likely involved in regulating NF1 transcription.
      These assays have also revealed a putative repressor region within the NF1
      promoter region corresponding to CCCTC-rich sequences between the transcription
      and translation start sites. This work provides new information concerning the
      transcriptional regulation of the NF1 gene, and is the most thorough attempt to
      date to map functionally relevant regions within the NF1 proximal promoter
      region.

PMID- 14647437
TI  - MMP expression profiling in recurred stage IB lung cancer.
AB  - We aimed to clarify the prime role of recurrence in stage I lung cancer. To
      determine the expression profiles, quantitative RT-PCR and real-time PCR were
      performed subsequently to evaluate the validity of meaningful molecules
      identified by 0.12 K c-DNA array experiment surveys. In all, 10 lung cancer
      patients presenting with recurrence of stage IB were selected and compared with
      10 stage IB lung cancer patients without recurrence since biopsied 3 years
      previously. On c-DNA microarray data analysis using pairs of recurred and the
      corresponding nonrecurred patients, the following genes were found to be
      upregulated in the recurred cases: matrix metalloproteinase (MMP)-10 in five
      cases, MMP-12 in two cases, MMP-11, MMP-14, MMP-15, fos, cyclin E2, E2F3, TGF
      alpha in each one case. The most frequently upregulated genes in recurred lung
      cancers were MMP-10 (stromelysin-2) and MMP-12 (macrophage elastase). On
      transcriptional assay by quantitative RT-PCR and real-time RT-PCR analysis to
      validate those molecules, both transcripts of MMP-10 and MMP-12 were
      significantly more upregulated in recurred stage IB lung cancer than in the non
      recurred stage IB lung cancer (P=0.004). Transcript levels were identical to c
      DNA array data. The protein levels of these entities were also evaluated by
      immunohistochemistry of archival slides. By immunohistochemistry, MMP-10
      monoclonal antibody showed more intense immunoreactivity in the recurred stage IB
      lung cancer than in the nonrecurred stage IB lung cancer (P=0.0313). Our approach
      revealed that MMP-10 plays an important role in the recurrence in stage IB lung
      cancer, irrespective of the histologic type.

PMID- 14647438
TI  - Evaluation of BRCA2 in the genetic susceptibility of familial esophageal cancer.
AB  - Previous studies of esophageal squamous cell carcinoma (ESCC) have shown a high
      frequency of allelic loss on chromosome 13q, infrequent somatic mutations in
      BRCA2, and a suggested association between a positive family history (FH+) of
      upper gastrointestinal cancer and germline BRCA2 mutations. In all, 70 ESCC
      patients (44 FH+ and 26 FH-) were examined by direct full sequencing of germline
      DNA for BRCA2 mutations. In addition, 28 family members of three of these
      patients and 232 unrelated healthy blood bank donor controls were examined for
      the mutations identified in the 70 ESCC patients. Five BRCA2 germline mutations,
      including three not previously reported (N1600del, A2054P, and V2109I), were
      identified in six of 44 FH+ patients, but none of 26 FH- patients (14 vs 0%,
      P=0.078), consistent with our previous findings (3/34 or 9% FH+ vs 0/22 or 0% FH
      , P=0.27). The cumulative frequency of BRCA2 germline mutations in ESCC patients
      in this and our previous study combined is 12%, with all mutations found in FH+
      as opposed to FH- cases (9/78 or 12% FH+ vs 0/48 or 0% FH-, P=0.013). We conclude
      that germline mutations in BRCA2 in ESCC patients from this high-risk area of
      China are more frequent in FH+ than FH- cases, suggesting that BRCA2 may play a
      role in genetic susceptibility to familial ESCC.

PMID- 14647439
TI  - Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human
      gastric cancer cells.
AB  - Both heme oxygenase-1 (HO-1) and p21(WAF1/Cip1) (p21) are involved in the
      pathogenesis of human cancer and their functions are closely associated with
      apoptosis. However, how these two molecules regulate apoptosis in human gastric
      cancer is unknown. In this study, we studied how HO-1 and p21 were regulated in
      two gastric cancer cell lines, MKN-45 with wild p53 and MKN-28 with mutant p53.
      The cells were treated with hemin and cadmium to induce HO-1. The result showed
      that HO-1 protein was significantly induced by hemin and cadmium in both cells
      tested. Following the HO-1 expression, p21 level was also markedly induced. The
      cells with increased HO-1 and p21 showed obviously resistantance to apoptotic
      stimuli. The levels of HO-1 and p21 induced were significantly inhibited by p38
      mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) and
      extracellular-regulated kinase (ERK) inhibitor (PD098059). Parallel to decreased
      HO-1 and p21 expression, the kinase inhibitors also significantly attenuated the
      resistance of the cells to apoptosis. The elevated HO-1 and p21 was further found
      to be associated with increase activity of the nuclear NF-kappaB and the
      inhibition of NF-kappaB led to the block of their induction. The elevated HO-1
      and p21 were also demonstrated to be related to increased cellular inhibitor of
      caspase inbitory protein-2 (c-IAP2) and decreased caspapse-3 activity. It was
      noted that the above changes observed were not different between MKN-45 and MKN
      28 cells, suggesting the functions of HO-1 and p21 were irrespective of the
      status of p53. In conclusion, we demonstrate that the resistance to apoptosis in
      gastric cancer cells with elevated HO-1 and p21 is independent of p53 status in a
      p38 MAPK- and ERK-mediated pathway with elevated c-IAP2 and decreased caspase-3
      activity and that this pathway is sensitive to the inhibition of NF-kappaB.

PMID- 14647440
TI  - Silencing effect of CpG island hypermethylation and histone modifications on O6
      methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic
      O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and
      mutagens. Recent studies have shown that in a subset of tumors, MGMT expression
      is inversely linked to hypermethylation of the CpG island in the promoter region;
      however, how the epigenetic silencing mechanism works, as it relates to
      hypermethylation, was still unclear. To understand the mechanism, we examined the
      detailed methylation status of the whole island with bisulfite-sequencing in 19
      MGMT non-expressed cancer cell lines. We found two highly methylated regions in
      the island. One was upstream of exon 1, including minimal promoter, and the other
      was downstream, including enhancer. Reporter gene assay showed that methylation
      of both the upstream and downstream regions suppressed luciferase activity
      drastically. Chromatin immunoprecipitation assay revealed that histone H3 lysine
      9 was hypermethylated throughout the island in the MGMT negative line, whereas
      acetylation on H3 and H4 and methylation on H3 lysine 4 were at significantly
      high levels outside the minimal promoter in the MGMT-expressed line. Furthermore,
      MeCP2 preferentially bound to the CpG-methylated island in the MGMT negative
      line. Given these results, we propose a model for gene silencing of MGMT that is
      dependent on the epigenetic state in cancer.

PMID- 14647441
TI  - FR901228 induces tumor regression associated with induction of Fas ligand and
      activation of Fas signaling in human osteosarcoma cells.
AB  - We investigated the antitumor effects of FR901228, a HDAC inhibitor, on human
      osteosarcoma cells, in vitro and in vivo to explore its possible utility in the
      treatment of pediatric bone cancers. FR901228 caused marked growth inhibition
      with a 50% inhibitory concentration of 1.2-7.3 nM and induction of apoptosis in
      all eight osteosarcoma cell lines tested. These effects of FR901228 were also
      observed in vivo xenograft models on BALB/c nude mice, and treatment with 5.6
      mg/kg/day resulting in a >70% reduction in the mean final tumor volume compared
      with the mean initial tumor volume. TUNEL assays demonstrated extensive apoptosis
      in tumor sections of mice treated with FR901228. Induction of apoptosis was
      preceded by increased expression of Fas ligand (FasL) mRNA, resulting in
      expression of membrane-bound FasL, which was followed by sequential activation of
      caspase-8 and -3. The level of apoptosis induction was reduced using a
      neutralizing anti-FasL antibody and overexpression of either the dominant
      negative FADD or the viral FLICE inhibitory protein. Furthermore, treatment with
      a suboptimal dose of FR901228 greatly sensitized osteosarcoma cells to agonistic
      anti-Fas antibody-mediated apoptosis. These findings suggest that FR901228 is a
      highly promising antitumor agent against osteosarcoma, inducing apoptosis by the
      activation of the Fas/FasL system.

PMID- 14647442
TI  - The human hepatocyte growth factor (HGF) gene is transcriptionally activated by
      leukemia inhibitory factor through the Stat binding element.
AB  - We found that human melanoma SEKI and neuroepithelioma NAGAI cells, which are
      known to secrete high concentrations of leukemia inhibitory factor (LIF), also
      secrete high levels of hepatocyte growth factor (HGF). We therefore examined the
      role of LIF in HGF expression and examined the human HGF promoter. The expression
      of both LIF and HGF mRNA is very low in HEK293 cells. Treatment of these cells
      with LIF stimulated the expression of HGF mRNA. The cis-acting regulatory element
      of the HGF promoter in SEKI and 293 cells was analysed by means of a transient
      expression assay. By deletion analysis, we showed that the region comprising the 
      181 to -73 bp was required for full activity of the HGF promoter in SEKI cells
      and for LIF responsiveness of 293 cells. This region contains putative consensus
      sequences for the Stat and NF-IL6 (C/EBP beta) transcription factors. The
      activity of the HGF promoter was abolished by mutation of the Stat site at -99/
      91, while the activity only slightly decreased on mutation of the NF-IL6 site.
      Treatment with anti-LIF antibodies or interruption of Stat3 signaling by dominant
      negative Stat3 also reduced the HGF promoter activity. Stat3 activation was
      constitutive in SEKI cells and induced on treatment of 293 cells with LIF. These
      results suggest that cytokines, growth factors and oncogenes (v-Src, etc.) that
      activate Stat3 are important regulators of HGF expression.

PMID- 14647443
TI  - Fidelity of DNA double-strand break repair in heterozygous cell lines harbouring
      BRCA1 missense mutations.
AB  - Germ-line mutations of the BRCA1 and BRCA2 genes, when they lead to a truncated
      protein, confer a high risk of breast and ovarian cancer. However, the role of
      BRCA1 missense mutations in cancer predisposition is unclear. Functional assays
      may be very helpful to more clearly define the biological effect of these
      mutations, and could therefore be useful in clinical practice. A recent study
      using a Host Cell End-Joining assay showed that a truncating mutation results in
      impaired fidelity of DSB repair by DNA end-joining. In the present study, we
      examined the fidelity of DSB repair in four lymphoblastoid cell lines with BRCA1
      missense mutations. The fidelity of DNA end-joining was impaired in the four cell
      lines studied compared to the normal control cell line. The fidelity of end
      joining was similar to that of a truncated mutation control cell line for one
      cell line and slightly higher for the other cell lines.

PMID- 14647444
TI  - Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary
      adenomas, is associated with CpG island methylation.
AB  - Inappropriate expression of cell-cycle regulatory genes and/or their protein
      products are a frequent finding in pituitary tumours; however, genetic changes
      associated with or responsible for their dysregulation are in general uncommon.
      In a search for novel genes, and employing cDNA-representational difference
      analysis, the gene encoding GADD45gamma was recently isolated and identified as
      being under-represented in pituitary adenomas. GADD45gamma is a member of a
      family of genes that are induced by DNA damage and function in the negative
      regulation of cell growth. In this study, we further confirm this initial report
      that the majority of pituitary adenomas (22 of 33; 67%) do not express
      GADD45gamma as determined by RT-PCR analysis. Loss of expression was not
      associated with either loss of heterozygosity or mutations within the coding
      region of this gene. In marked contrast, epigenetic change, namely methylation of
      the GADD45gamma genes CpG island, was a frequent finding (19 of 33 adenoma; 58%)
      and was significantly associated with tumours in which GADD45gamma transcript was
      not expressed (18 of 22; 82%; P=0.002). In common with the primary tumours,
      methylation-associated gene silencing of the GADD45gamma gene was also found in
      the pituitary tumour cell line AtT20. The treatment of AtT20 cells with the
      demethylating agent, 5-Aza-2'-deoxycytidine, induced the re-expression of this
      gene. These findings show that silencing of the GADD45gamma gene in pituitary
      tumours is primarily associated with methylation of the genes CpG island.
      Methylation has functional importance since reversal of this epigenetic change in
      a pituitary-derived cell line is associated with re-expression. Silencing of
      GADD45gamma, a negative regulator of cell growth, is most likely responsible for
      conferring a selective growth advantage during tumour evolution and outgrowth.

PMID- 14647445
TI  - Loss of chromosome 18q and DPC4 (Smad4) mutations in appendiceal adenocarcinomas.
AB  - Appendiceal adenocarcinomas are uncommon, and the genetic alterations present in
      these tumors are not well characterized. We studied genetic alterations including
      loss of chromosome 18q (location of DCC, DPC4, and JV-18 genes), and mutations of
      the DPC4 (SMAD4) and beta-catenin genes in 28 appendiceal adenocarcinomas,
      consisting of 17 mucinous and 11 nonmucinous carcinomas. Chromosome 18q loss was
      present in 57% (12/21) of appendiceal carcinomas including 54% (7/13) of mucinous
      and 63% (5/8) of nonmucinous carcinomas. Mutation of the DPC4 gene was present in
      14% (three of 22) of the carcinomas occurring in one tumor with chromosome 18q
      loss and in two with unassessed chromosome 18q status. beta-catenin gene mutation
      was present in 0% (0 of 25) of the carcinomas. Chromosome 18q loss status was not
      associated with any clinicopathological features. The presence of chromosome 18q
      loss and DPC4 mutations in appendiceal adenocarcinomas suggests involvement of
      DPC4 and nearby genes on chromosome 18q (DCC and/or JV-18) in the pathogenesis of
      appendiceal adenocarcinomas.

PMID- 14647446
TI  - Induction of apoptosis by enediyne antibiotic calicheamicin thetaII proceeds
      through a caspase-mediated mitochondrial amplification loop in an entirely Bax
      dependent manner.
AB  - Calicheamicin thetaII is a member of the enediyne class of antitumor antibiotics
      that bind to DNA and induce apoptosis. These compounds differ, however, from
      conventional anticancer drugs as they bind in a sequence-specific manner
      noncovalently to DNA and cause sequence-selective oxidation of deoxyriboses and
      bending of the DNA helix. Calicheamicin is clinically employed as immunoconjugate
      to antibodies directed against, for example, CD33 in the case of gemtuzumab
      ozogamicin. Here, we show by the use of the unconjugated drug that calicheamicin
      induced apoptosis is independent from death-receptor/FADD-mediated signals.
      Moreover, calicheamicin triggers apoptosis in a p53-independent manner as shown
      by the use of p53 knockout cells. Cell death proceeds via activation of
      mitochondrial permeability transition, cytochrome c release and activation of
      caspase-9 and -3. The overexpression of Bcl-x(L) or Bcl-2 strongly inhibited
      calicheamicin-induced apoptosis. Knockout of Bax abrogated cell death after
      calicheamicin treatment. Thus, the activation of mitochondria and execution of
      cell death occur through a fully Bax-dependent mechanism. Interestingly, caspase
      inhibition by the pancaspase-inhibitor zVAD-fmk interfered with mitochondrial
      activation by calicheamicin. This places caspase activation upstream of the
      mitochondria and indicates that calicheamicin-triggered apoptosis is enhanced
      through death receptor-independent activation of the caspase cascade, that is, an
      amplification loop that is required for full activation of the mitochondrial
      pathway.

PMID- 14647447
TI  - Checkpoint-mediated control of replisome-fork association and signalling in
      response to replication pausing.
AB  - The replication checkpoint controls the integrity of replicating chromosomes by
      stabilizing stalled forks, thus preventing the accumulation of abnormal
      replication and recombination intermediates that contribute to genome
      instability. Checkpoint-defective cells are susceptible to rearrangements at
      chromosome fragile sites when replication pauses, and certain human cancer prone
      diseases suffer checkpoint abnormalities. It is unclear as to how the checkpoint
      stabilizes stalled forks and how cells sense replication blocks. We have analysed
      the checkpoint contribution in controlling replisome-fork association when
      replication pauses. We show that in yeast wild-type cells, stalled forks exhibit
      stable replisome complexes and the checkpoint sensors Ddc1 and Ddc2, thus
      activating Rad53 checkpoint kinase. Ddc1/Ddc2 recruitment on stalled forks and
      Rad53 activation are influenced by the single-strand-binding protein replication
      factor A (RFA). rad53 forks exhibit a defective association with DNA polymerases
      alpha, epsilon and delta. Further, in rad53 mutants, stalled forks progressively
      generate abnormal structures that turn into checkpoint signals by accumulating
      RFA, Ddc1 and Ddc2. We suggest that, following replication blocks, checkpoint
      activation mediated by RFA-ssDNA filaments stabilizes stalled forks by
      controlling replisome-fork association, thus preventing unscheduled recruitment
      of recombination enzymes that could otherwise cause the pathological processing
      of the forks.

PMID- 14647448
TI  - Effects of Herceptin treatment on global gene expression patterns in HER2
      amplified and nonamplified breast cancer cell lines.
AB  - Herceptin is a humanized monoclonal antibody targeted against the extracellular
      domain of the HER2 oncogene, which is amplified and overexpressed in 10-34% of
      breast cancers. Herceptin therapy provides effective treatment in HER2-positive
      metastatic breast cancer, although a favorable treatment response is not achieved
      in all cases. Here, we show that Herceptin treatment induces a dose-dependent
      growth reduction in breast cancer cell lines with HER2 amplification, whereas
      nonamplified cell lines are practically resistant. Time-course analysis of global
      gene expression patterns in amplified and nonamplified cell lines indicated a
      major change in transcript levels between 24 and 48 h of Herceptin treatment. A
      step-wise gene selection algorithm revealed a set of 439 genes whose temporal
      expression profiles differed most between the amplified and nonamplified cell
      lines. The discriminatory power of these genes was confirmed by both hierarchical
      clustering and self-organizing map analyses. In the amplified cell lines, the
      Herceptin treatment induced the expression of several genes involved in RNA
      processing and DNA repair, while cell adhesion mediators and known oncogenes,
      such as c-FOS and c-KIT, were downregulated. These results provide additional
      clues to the downstream effects of blocking the HER2 pathway in breast cancer and
      may provide new targets for more effective treatment.

PMID- 14647449
TI  - Estrogen regulation of vascular endothelial growth factor gene expression in ZR
      75 breast cancer cells through interaction of estrogen receptor alpha and SP
      proteins.
AB  - Vascular endothelial growth factor (VEGF) is expressed in multiple hormone
      dependent cancer cells/tumors. Treatment of ZR-75 breast cancer cells with 17beta
      estradiol (E2) induced a greater than fourfold increase of VEGF mRNA levels. ZR
      75 breast cancer cells were transfected with pVEGF1, a construct containing a 
      2018 to +50 VEGF promoter insert, and E2 induced reporter gene (luciferase)
      activity. Deletion and mutation analysis of the VEGF gene promoter identified a
      GC-rich region (-66 to -47) which was required for E2-induced transactivation of
      pVEGF5, a construct containing the minimal promoter (-66 to +54) that exhibited
      E2-responsiveness. Interactions of nuclear proteins from ZR-75 cells with the
      proximal GC-rich region of the VEGF gene promoter were investigated by
      electrophoretic mobility shift and chromatin immunoprecipitation assays. The
      results demonstrate that both Sp1 and Sp3 proteins bound the GC-rich motif (-66
      to -47), and estrogen receptor alpha (ERalpha) interactions were confirmed by
      chromatin immunoprecipitation. Moreover, E2-dependent activation of constructs
      containing proximal and distal GC/GT-rich regions of the VEGF promoter was
      inhibited in ZR-75 cells transfected with small inhibitory RNAs for Sp1 and Sp3.
      These results were consistent with a mechanism of hormone activation of VEGF
      through ERalpha/Sp1 and ERalpha/Sp3 interactions with GC-rich motifs.

PMID- 14647450
TI  - A role for Janus kinases in crosstalk between ErbB3 and the interferon-alpha
      signaling complex in myeloma cells.
AB  - Receptor crosstalk is an emerging and recurrent theme in cytokine and growth
      factor signaling; however, insight into the mechanism(s) underlying these
      interactions remains limited. Recently, we reported that crosstalk occurs between
      ErbB3 and the interferon alpha (IFN-alpha) signaling complex in the myeloma cell
      line KAS-6/1 and that this crosstalk contributes to the regulation of cell
      proliferation. In this study, we examined the mechanism underlying the
      transactivation of ErbB3 in the IFN-alpha growth-responsive KAS-6/1 cells. The
      examination of IFN-alpha receptor 1 and 2 (IFNAR1 and IFNAR2) levels revealed
      that the KAS-6/1 cell line overexpresses IFNAR1 relative to other myeloma cell
      lines that are growth arrested by IFN-alpha. Subsequent investigation of Tyk2,
      which is constitutively associated with IFNAR1, demonstrated that Tyk2 activation
      is uniquely sustained in the KAS-6/1 cell line following IFN-alpha stimulation.
      Interestingly, silencing of Tyk2 expression via siRNA resulted in attenuation of
      ErbB3 transactivation. However, inhibition of Jak1 expression also decreased IFN
      alpha-induced tyrosine phosphorylation of ErbB3. Finally, siRNA downregulation of
      Tyk2 and Jak1 was found to decrease IFN-alpha-stimulated proliferation. These
      findings validate our previous report of ErbB3 involvement in IFN-alpha-induced
      proliferation and further suggest that both Janus kinase members, Tyk2 and Jak1,
      play a role in the transactivation of ErbB3 in this model system.

PMID- 14647452
TI  - Spi-1/PU.1 but not Fli-1 inhibits erythroid-specific alternative splicing of 4.1R
      pre-mRNA in murine erythroleukemia cells.
AB  - The inclusion of exon 16 in mature protein 4.1R mRNA arises from a stage-specific
      splicing event that occurs during late erythroid development. We have shown that
      mouse erythroleukemia (MEL) cells reproduce this erythroid-specific splicing
      event upon induction of differentiation. We here found that this splicing event
      is regulated specifically in erythroleukemic cells that have the potential to
      differentiate and produce hemoglobin, regardless of the nature of the
      differentiation inducer. Knowing that dysregulated expression of spi-1/pu.1 and
      fli-1 oncogenes is involved in MEL cell differentiation arrest, we looked at
      their effect on exon 16 erythroid splicing. We found that exon 16 inclusion
      requires Spi-1/PU.1 shutdown in MEL cells, and that enforced expression of Spi
      1/PU.1 inhibits exon selection, regardless of the presence or absence of a
      chemical inducer. By contrast, endogenous overexpression or enforced expression
      of Fli-1 has no effect on exon selection. We further showed that Spi-1/PU.1 acts
      similarly on the endogenous and on a transfected exon 16, suggesting a promoter
      independent effect of Spi-1/PU.1 on splicing regulation. This study provides the
      first evidence that Spi-1/PU.1 displays the unique property, not shared with Fli
      1, to inhibit erythroid-specific pre-mRNA splicing in erythroleukemia cell
      context.

PMID- 14647451
TI  - Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial
      permeability transition pore opening and cytochrome c release induced by arsenic
      trioxide.
AB  - The precise molecular mechanism underlying arsenic trioxide (As(2)O(3))-induced
      apoptosis is a subject of extensive study. Here, we show that clinically relevant
      doses of As(2)O(3) can induce typical apoptosis in IM-9, a multiple myeloma cell
      line, in a Bcl-2 inhibitable manner. We confirmed that As(2)O(3) directly induced
      cytochrome c (cyto c) release from isolated mouse liver mitochondria via the
      mitochondrial permeability transition pore, and we further identified the voltage
      dependent anion channel (VDAC) as a biological target of As(2)O(3) responsible
      for eliciting cyto c release in apoptosis. First, pretreatment of the isolated
      mitochondria with an anti-VDAC antibody specifically prevented As(2)O(3)-induced
      cyto c release. Second, in proteoliposome experiments, VDAC by itself was
      sufficient to mediate As(2)O(3)-induced cyto c release, which could be
      specifically inhibited by Bcl-X(L). Third, As(2)O(3) induced mitochondria
      membrane potential (DeltaPsim) reduction and cyto c release only in the VDAC
      expressing, but not in the VDAC-deficient yeast strain. Finally, we found that
      As(2)O(3) induced the increased expression and homodimerization of VDAC in IM-9
      cells, but not in Bcl-2 overexpressing cells, suggesting that VDAC
      homodimerization could potentially determine its gating capacity to cyto c, and
      Bcl-2 blockage of VDAC homodimerization represents a novel mechanism for its
      inhibition of apoptosis.

PMID- 14647453
TI  - Estrogen-independent activation of erbBs signaling and estrogen receptor alpha in
      the mouse vagina exposed neonatally to diethylstilbestrol.
AB  - Growth factors and estrogen receptor (ER) signaling cooperate to play essential
      roles in cell proliferation, differentiation and tumor progression in mouse
      reproductive organs. Treatment of neonatal mice with diethylstilbestrol (DES)
      induces an estrogen-independent persistent proliferation and cornification of the
      vaginal epithelium, which results in cancerous lesions later in life. However,
      the mechanisms of the estrogen-dependent and -independent pathways essentially
      remain unknown. We characterized the expression of epidermal growth factor (EGF)
      like growth factors (EGF, transforming growth factor alpha (TGF-alpha), heparin
      binding EGF-like growth factor (HB-EGF), betacellulin (BTC), amphiregulin (APR),
      epiregulin (EPR) and neuregulin (NRG) 1) and erbB receptors (EGF receptor (EGFR),
      erbB2/neu, erbB3 and erbB4) in the vaginae of mice treated either neonatally (0-4
      day) or as adults (55-59 day) with estrogens. EGFR and erbB2 were activated in
      the vaginal epithelium of mice by estrogen treatment. This activation was also
      encountered in vaginae from neonatally DES-exposed mice, along with the
      expression of EGF, TGF-alpha, HB-EGF, BTC, APR, EPR and NRG1. Immunohistochemical
      analysis indicated that erbB2 was primarily expressed in vaginal epithelium.
      Finally, we found that serine 118 and 167 located in the AF-1 domain of ERalpha
      were phosphorylated in these vaginae. AG825, AG1478 or ICI 182,780 administration
      blocked proliferation of vaginal epithelium induced by neonatal DES exposure.
      Thus, signal transduction via EGFR and erbB2 could be related to the estrogen
      induced vaginal changes and persistent erbBs phosphorylation and sustained
      expression of EGF-like growth factors, leading to ERalpha activation that may
      result in cancerous lesions in vaginae from neonatally DES-exposed mice later in
      life.

PMID- 14647454
TI  - Genetic complementation of cytokine signaling identifies central role of kinases
      in hematopoietic cell proliferation.
AB  - Molecular evidence suggests a multistep process in the development of acute
      leukemia. Since inappropriate activation of cytokine signaling cascades is a
      recurring theme in human leukemia, we performed expression screens to identify
      genes that transform cytokine-dependent cells. Using retroviral cDNA libraries
      derived from peripheral blood mononuclear cells of patients with
      myeloproliferative disorders, we isolated numerous genes that genetically
      complement cytokine requirements for proliferation of BaF/3 and TF-1 cells. The
      majority of recovered genes represent members of the kinase family, including
      several previously linked to leukemogenesis. Our unbiased screen highlights the
      central role of kinase activation in hematopoietic cell proliferation and
      identifies a number of potential leukemic oncoproteins.

PMID- 14647455
TI  - Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced
      apoptosis.
AB  - There has been a considerable debate as to whether caspase-2 is an initiator or
      effector caspase. Recently, a new model of intrinsic pathway of apoptosis has
      been proposed, which suggests caspase-2 to be an initiator caspase. For example,
      ultraviolet radiation (UV) and other DNA damage-inducing agents were shown to
      first activate caspase-2 and then regulate the mitochondrial and
      postmitochondrial events. Active caspase-2 was found to engage mitochondria by
      promoting Bax translocation to the mitochondria. Consequently, Bax was proposed
      to play a central role in bridging the active caspase-2 with mitochondria by
      affecting mitochondrial permeability, cytochrome c release into the cytosol and
      caspase-9 activation. In the present study, we investigated the role of Bax in UV
      induced apoptosis and caspase-2 activation. Our results indicate that UV-induced
      apoptosis and caspase-2 activation were diminished in Bax-deficient cells,
      suggesting that Bax appears to play an important role in UV-induced apoptosis as
      well as caspase-2 activation, and that it also appears to reside upstream of
      caspase-2. Bax deficiency also affected the activation of caspase-3 and -8 and
      abolished caspase-9 activation during UV-induced apoptosis, suggesting that the
      absence of caspase-9 activation may affect caspase-2, -3 and -8 activation in Bax
      deficient cells. Based on our results, we propose that activation of caspases is
      not a linear cascade of events, but is rather connected via complex feedback
      loops.

PMID- 14647457
TI  - mtDNA mutations in tumors of the central nervous system reflect the neutral
      evolution of mtDNA in populations.
AB  - Mitochondrial DNA (mtDNA) instability has been observed in different types of
      cancer, including colorectal, breast, and gastric cancer. The relationship
      between the occurrence of such alteration and the nuclear microsatellite
      instability (nMI) status of the neoplastic cells remains controversial. In an
      attempt to clarify this issue, we sequenced the first and second mtDNA
      hypervariable regions, and typed the mitochondrial (CA)(n) dinucleotide
      polymorphism in 69 patients with primary tumors of the central nervous system
      (CNS), previously screened for nMI. Tumor samples showed 27 D-loop sequence
      changes (39.1%) compared to the corresponding blood samples. Microsatellite
      homoplasmic allele mutations were detected in four cases (5.8%). We did not find
      significant associations of the mtDNA instability status with clinicopathological
      parameters including sex, age, tumor size, and duration of clinical course.
      Neither did we find any association between mtDNA and nuclear instabilities,
      indicating that, at least in CNS tumors, they respond to different DNA repair
      mechanisms. We have also compiled the mtDNA instabilities previously reported by
      other authors for several types of tumors, comparing them to mtDNA polymorphisms
      in human populations. Most of the tumor-associated changes are common human
      polymorphisms and mutational hotspots. To explain the molecular behavior of mtDNA
      instability in tumors, we propose a model also common to other biological
      situations.

PMID- 14647456
TI  - IFNgamma sensitization to TRAIL-induced apoptosis in human thyroid carcinoma
      cells by upregulating Bak expression.
AB  - TRAIL preferentially induces apoptosis in tumor cells and virus-infected cells.
      Unlike other tumor necrosis factor family members, TRAIL does not kill cells from
      most normal tissues and has thus been proposed as a promising new cancer
      treatment. Our study demonstrated that IFNgamma combined with TRAIL can trigger
      apoptosis in vitro in several resistant thyroid tumor cell lines, such as thyroid
      anaplastic carcinoma cells (ARO cells), while either agent alone exerts only a
      minimal effect. We further tested this effect on a mouse thyroid tumor model,
      when in vivo tumor growth was also significantly inhibited by this combination.
      The mechanism of how IFNgamma sensitized thyroid carcinoma cells to TRAIL-induced
      apoptosis was investigated by screening global gene alterations in ARO cells
      treated with IFNgamma. Microarray data revealed that a proapoptotic gene, Bak, is
      markedly upregulated by IFNgamma, and this was confirmed by RNase protection
      assay. Western blot analysis also showed a significant increase in Bak at the
      protein level. Upregulation of Bak and sensitization for apoptosis by IFNgamma
      was blocked by overexpression of antisense Bak in ARO cells. Furthermore,
      overexpression of Bak sensitized ARO cell to TRAIL-induced apoptosis without the
      need for IFNgamma pretreatment. This suggests that Bak is a regulatory molecule
      involved in IFNgamma-facilitated TRAIL-mediated apoptosis in thyroid cancer
      cells.

PMID- 14647458
TI  - Role of the ceramide-signaling pathways in ionizing radiation-induced apoptosis.
AB  - Ionizing radiations (IR) exposure leads to damage on several cellular targets.
      How signals from different targets are integrated to determine the cell fate
      remains a controversial issue. Understanding the pathway(s) responsible(s) for
      the cell killing effect of the IR exposure is of prime importance in light of
      using radiations as anticancer agent or as diagnostic tool. In this study, we
      have established that IR-induced cell damage initiates two independent signaling
      pathways that lead to a biphasic intracellular ceramide increase. A transitory
      increase of ceramide is observed within minutes after IR exposure as a
      consequence of DNA damage-independent acid sphingomyelinase activation. Several
      hours after irradiation, a second wave of ceramide accumulation is observed
      depending on the DNA damage-dependent activation of ceramide synthase, which
      requires a signaling pathway involving ATM. Importantly, we have demonstrated
      that the late ceramide accumulation is also dependent on the first one and is
      rate limiting for the apoptotic process induced by IR. In conclusion, our
      observations suggest that ceramide is a major determinant of the IR-induced
      apoptotic process at the cross-point of different signal transduction pathways.

PMID- 14647459
TI  - Induction of G0/G1 cell cycle arrest in ovarian carcinoma cells by the anti
      inflammatory drug NS-398, but not by COX-2-specific RNA interference.
AB  - Cyclooxygenases, particularly COX-2, play an important role in tumor development
      and progression. We have previously shown that COX-2 expression is an independent
      prognostic factor in human ovarian carcinoma. In this study, we investigated the
      effects of the inhibition of COX isoforms by the NSAID NS-398 as well as by COX
      isoform-specific RNA interference (RNAi) in the human ovarian carcinoma cell
      lines OVCAR-3 and SKOV-3. OVCAR-3 cells showed a constitutive expression of COX-1
      and an induction of high levels of COX-2 and PGE(2) after stimulation with
      interleukin-1beta. In contrast, SKOV-3 cells were negative for both COX isoforms.
      In OVCAR-3 cells, PGE(2) production was inhibited by NS-398 in concentrations of
      1 microM and by a COX-2-specific silencing RNA (siRNA), while a COX-1-specific
      siRNA did not have an effect. This suggests that COX-2 is the major source of
      PGE(2) in this cell line. To dissociate COX-2-specific and non-COX-2-specific
      effects on cell proliferation, a proliferation assay was performed after
      incubation of cells with NS-398 and COX siRNAs. NS-398 induced an inhibition of
      cell proliferation at concentrations of 50-500 microM, which are above the
      concentrations needed for the inhibition of PGE(2) production. This inhibitory
      effect was present in the COX-positive cell line OVCAR-3 as well as in the COX
      negative cell line SKOV-3 and could not be reverted by addition of exogenous
      PGE(2). Neither COX-1- nor COX-2-specific siRNAs had an effect on cell
      proliferation of OVCAR-3 cells. Cell cycle analysis showed an increased
      accumulation of cells in the G0/G1 phase after treatment with NS-398, but not
      with COX siRNAs. These experiments suggest that NS-398 reduced cell proliferation
      in ovarian carcinoma cells by induction of G0/G1 cell cycle arrest independent of
      COX-2 inhibition. Our study shows that specific inhibition of COX isoforms by
      RNAi could be used to dissociate effects of NSAIDs. Furthermore, our results
      suggest that cell cycle arrest is one of the primary mechanisms responsible for
      the antiproliferative effects of NS-398 on ovarian carcinoma cells.

PMID- 14647460
TI  - Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and
      enhances their metastatic potential in nude mouse model.
AB  - Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of
      colon carcinoma and many other human cancers. The present study demonstrates that
      treatment of human colon carcinoma cells with active matrilysin induces cell
      aggregation in vitro and promotes liver metastasis in nude mice. When two kinds
      of colon carcinoma cell lines were incubated with active matrilysin, this enzyme
      efficiently bound to the cell surface and induced loose cell aggregation, which
      led to E-cadherin-mediated tight cell aggregation. Synthetic MMP inhibitors
      inhibited both the membrane binding of matrilysin and matrilysin-induced cell
      aggregation, while TIMP-2 inhibited only the cell aggregation. Two other active
      MMPs, stromelysin and gelatinase A, neither bound to cell membrane nor induced
      cell aggregation. Tumor cells in loose cell aggregates could reaggregate even
      after they were freed from matrilysin and dispersed. When injected into the
      spleen of nude mice, the tumor cells in the stable aggregates produced much
      larger metastatic nodules in the livers than control cells and those in the loose
      aggregates. These results suggest that matrilysin may enhance metastatic
      potential of tumor cells by processing a cell surface protein(s) and thereby
      inducing loose and then tight aggregation of tumor cells.

PMID- 14647461
TI  - MLL-AF9 oncogene expression affects cell growth but not terminal differentiation
      and is downregulated during monocyte-macrophage maturation in AML-M5 THP-1 cells.
AB  - The MLL-AF9 oncogene - one of the most frequent MLL/HRX/ALL-1 rearrangements
      found in infantile and therapy-related leukaemias - originates from
      t(9;11)(p22;q23) and is mainly associated with monocytic acute myeloid leukaemia
      (AML-M5; FAB-classification). Here, we investigated the MLL-AF9 function by means
      of an antisense phosphorothioate-oligodeoxyribonucleotide (MLL-AF9-PS-ODNas)
      using the THP-1 AML-M5 cell line carrying t(9;11). Having confirmed that MLL-AF9
      PS-ODNas induces strong inhibition of THP-1 cell growth, but only a moderate
      increase in apoptosis, we found that MLL-AF9-PS-ODNas did not induce morpho
      functional terminal differentiation or restore M-CSF-, G-CSF- or GM-CSF-induced
      differentiation. Moreover, THP-1 cells showed the same phenotype with/without MLL
      AF9-PS-ODNas. In THP-1 cells differentiated to mature macrophage-like cells by
      PMA/TPA or ATRA, MLL-AF9 expression was downregulated. Thus, in the monocytic
      lineage, MLL-AF9 may be expressed only in early phases and can induce deregulated
      amplification in both nonmalignant and malignant cells, maintaining the monocytic
      phenotype without blocking final maturation. Our findings suggest that: (1) as
      well as directly promoting cell growth, MLL-AF9 may also indirectly determine
      phenotype; (2) other leukaemogenic mutations associated with MLL-AF9-related
      leukaemias should be searched for mainly in processes of resistance to apoptosis
      (where MLL-AF9 may play only a limited role) and differentiation blockage (where
      MLL-AF9 may play no role).

PMID- 14647462
TI  - Maspin - the most commonly-expressed gene of the 18q21.3 serpin cluster in lung
      cancer - is strongly expressed in preneoplastic bronchial lesions.
AB  - Maspin, SCCA1/2 and hurpin were identified by cDNA microarray analyses as
      dramatically differentially expressed transcripts in primary non-small cell lung
      cancer (NSCLC). These sequences are located within a 10-gene serpin cluster on
      18q21.3. Using comparative RT-PCR, we have investigated the expression of each of
      these serpins, including their flanking loci, in an independent NSCLC series.
      Whereas six of the genes (maspin, SCCA1, SCCA2, hurpin, megsin and pAI-2) were
      commonly differentially expressed in primary lesions, each significantly more
      often in squamous cell tumours, maspin was identified as the most frequently over
      represented sequence in both squamous cell carcinoma and adenocarcinoma. Using a
      well-characterized monoclonal antibody, we have shown strong maspin expression in
      tumour protein extracts, detected multiple isoforms of the 42 kDa protein and
      shown that maspin is localized specifically to the tumour cells within neoplastic
      lesions. In contrast, most cells in non-neoplastic lung tissue appear not to
      express the gene, with the exception of the multipotent basal epithelial cells
      that line the bronchial airway. These reserve cells generally show strong
      predominantly nuclear localization of maspin. Strong nuclear expression of maspin
      within primary tumour cells is correlated with increased survival (P=0.05) and a
      longer remission duration (P=0.02) in resectable-staged patients. However, within
      the airways of cancer patients and somewhat in contrast to this observation, such
      expression was more frequently detected in the superficial cells of preneoplastic
      over non-neoplastic epithelia (P<0.0001), consistent with a role for the protein
      in early neoplasia.

PMID- 14647463
TI  - Direct association between PU.1 and MeCP2 that recruits mSin3A-HDAC complex for
      PU.1-mediated transcriptional repression.
AB  - PU.1, a member of the Ets family of transcription factors, is implicated in
      hematopoietic cell differentiation through its interactions with other
      transcriptional factors and cofactors. To identify a novel protein(s) binding to
      PU.1, we carried out affinity purification using a column of Glutathione
      Sepharose beads bound to GST-PU.1 fusion protein and isolated several individual
      proteins using murine erythroleukemia (MEL) cell extracts. Sequence analysis of
      these proteins revealed that one was MeCP2 a methyl CpG binding protein. GST-pull
      down assay and immunoprecipitation assay showed that PU.1 bound directly to MeCP2
      via its Ets domain and MeCP2 bound to PU.1 via either its amino terminal domain
      or trans-repression domain. MeCP2 repressed transcriptional activity of PU.1 on a
      reporter construct with trimerized PU.1 binding sites. This downregulation was
      recovered in the presence of histone deacetylase inhibitor, trichostatin A (TSA).
      MeCP2 was integrated in PU.1-mSin3A-HDAC complex but not in PU.1-CBP complex.
      Chromatin immunoprecipitation (ChIP) assays showed that PU.1 and MeCP2 were
      collocated at the PU.1 binding site on the reporter construct and the PU.1
      binding site of the intervening sequence 2 (IVS2) region in the intron of the
      beta-globin gene, which has been proposed to regulate expression of the gene, in
      undifferentiated MEL cells. The complex disappeared from the region during the
      course of erythroid differentiation of MEL cells. Our results suggest that MeCP2
      acts as a corepressor of PU.1 probably due to facilitating complex formation with
      mSin3A and HDACs.

PMID- 14647464
TI  - Distinct patterns of microsatellite instability are seen in tumours of the
      urinary tract.
AB  - To date, two forms of microsatellite instability (MSI) have been described in
      human cancer. MSI typical of hereditary nonpolyposis colon cancer (HNPCC), is due
      to deficient DNA mismatch repair (MMR) and is defined with mono- and dinucleotide
      repeat microsatellites. A second variety of instability is best seen at selective
      tetranucleotide repeats (EMAST; elevated microsatellite alterations at select
      tetranucleotides). While MSI occurs infrequently in bladder cancers, EMAST is
      common. Sporadic tumours with the largest proportion showing MSI are those found
      most frequently in HNPCC kindreds. While bladder cancer is not frequently seen in
      HNPCC, upper urinary tract tumours (UTTs) are. Having previously found a low
      frequency of MSI in bladder cancer, we sought to determine the relative levels of
      MSI and EMAST in transitional cell carcinoma (TCC) of the upper and lower urinary
      tracts. Microsatellite analysis was performed at 10 mono- and dinucleotide and
      eight tetranucleotide loci, in 89 bladder and 71 UTT TCC. Contrasting patterns of
      instability were seen in urinary tumours. In bladder cancer, MSI was rare and
      EMAST was common. The presence of EMAST was not related to tumour grade, stage,
      subsequent outcome or immunohistochemical expression of the MMR proteins. In UTT,
      while MSI occurred frequently, EMAST was seen less frequently than in bladder
      cancer. When TCC of the upper and lower urinary tracts are compared, MSI-H is
      more frequent in UTT and EMAST more frequent in bladder cancer. Our findings show
      that, as for colorectal cancer, the pattern of MSI varies with location in the
      urinary tract. In addition, we have confirmed that MSI and EMAST are discrete
      forms of MSI, and that the presence of EMAST does not affect tumour phenotype.

PMID- 14647465
TI  - Tr-kit promotes the formation of a multimolecular complex composed by Fyn,
      PLCgamma1 and Sam68.
AB  - Tr-kit is a truncated form of the tyrosine kinase receptor c-kit expressed in the
      haploid phase of spermatogenesis. Upon microinjection, tr-kit triggers metaphase
      to-anaphase transition in mouse eggs by the sequential activation of Fyn and
      PLCgamma1. Here, we show that tr-kit promotes the interaction of several tyrosine
      phosphorylated proteins with the SH3 domain of PLCgamma1. Western blot analysis
      indicates that one of these proteins is Sam68, an RNA-binding protein that is
      known to interact with and be phosphorylated by Src-like kinases in mitosis. tr
      kit promotes the association of Sam68 with PLCgamma1 and Fyn in a multimolecular
      complex, as demonstrated by co-immunoprecipitation of the phosphorylated forms of
      these proteins using antibodies directed to anyone of the partners of the
      complex. Expression of tr-kit potentiates the interaction of endogenous Sam68
      also with the SH3 domain of Fyn. Furthermore, the subcellular localization of
      Sam68 is affected by tr-kit through activation of Fyn in live cells. Lastly, we
      show that interaction with the SH3 domain of Fyn triggers the release of Sam68
      from bound RNA. Thus, our data suggest that tr-kit promotes the formation of a
      multimolecular complex composed of Fyn, PLCgamma1 and Sam68, which allows
      phosphorylation of PLCgamma1 by Fyn, and may modulate RNA metabolism.

PMID- 14647466
TI  - Sequence-specific silencing of MT1-MMP expression suppresses tumor cell migration
      and invasion: importance of MT1-MMP as a therapeutic target for invasive tumors.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) has been believed a key
      enzyme in tumor invasion, because it is expressed in a variety of malignant human
      tumors, and overexpression of the enzyme enhances the ability of cellular
      invasiveness. However, it has not necessarily been clarified whether the
      endogenously expressed MT1-MMP in human tumors plays a critical role in their
      invasiveness. We used RNA silencing technology to downregulate the endogenous MT1
      MMP expression in human tumor cells (fibrosarcoma HT1080 and gastric carcinoma
      MKN-28 cell lines), and evaluated the effect on the invasion of a reconstituted
      basement membrane (Matrigel). Transfection of a double-stranded RNA targeted to
      the MT1-MMP gene decreased the level of the enzyme to less than 10-20% without
      affecting production of other MMPs. According to the degree of silencing,
      activation of proMMP-2 was inhibited. CD44 shedding was also inhibited, but only
      in part. Decreased MT1-MMP levels were also reflected in reduced cell motility on
      hyaluronan (HA) and invasion in Matrigel. Thus, specific downregulation of MT1
      MMP expression was sufficient to cause significant inhibition of the migration
      and invasion of tumor cells, even though other MMPs continued to be expressed.

PMID- 14647467
TI  - Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic
      neurons.
AB  - Cyclin D-dependent kinases phosphorylate the retinoblastoma (Rb) protein and play
      a critical role in neuronal cell cycle control and apoptosis. Here we show that
      cyclin D1 became predominantly cytoplasmic as primary cortical progenitor cells
      underwent cell cycle withdrawal and terminal differentiation. Furthermore,
      ectopically expressed cyclin D1 sequestered in the cytoplasm of postmitotic
      neurons, whereas it efficiently entered the nucleus of proliferating progenitor
      cells. Cytoplasmic cyclin D1 were complexed with cyclin-dependent kinase 4
      (CDK4), and also with CDK inhibitors, p27(Kip)(I) or p21(Cip)(I), which
      positively regulate assembly and nuclear accumulation of the cyclin D1-CDK4
      complex. Although overexpression of p21(Cip)(I) promoted cyclin D1 nuclear
      localization, inhibition of either glycogen synthase kinase 3beta- or CRM1
      mediated cyclin D1 nuclear export did not, suggesting that the inhibition of its
      nuclear import, rather than the acceleration of nuclear export, contributes to
      cytoplasmic sequestration of cyclin D1 in postmitotic neurons. In differentiated
      progenitor cells, nuclear localization of ectopic cyclin D1 induced apoptosis,
      and the DNA-damaging compound camptothecin caused nuclear accumulation of
      endogenous cyclin D1, accompanied by Rb phosphorylation. These results indicate
      that nuclear accumulation of cyclin D1 is inhibited in postmitotic neurons and
      suggest a role of its subcellular localization in neuronal death and survival.

PMID- 14647468
TI  - Sp100 is important for the stimulatory effect of homeodomain-interacting protein
      kinase-2 on p53-dependent gene expression.
AB  - HIPK2 shows overlapping localization with p53 in promyelocytic leukemia (PML)
      nuclear bodies (PML-NBs) and functionally interacts with p53 to increase gene
      expression. Here we demonstrate that HIPK2 and the PML-NB resident protein Sp100
      synergize for the activation of p53-dependent gene expression. Sp100 and HIPK2
      interact and partially colocalize in PML-NBs. The cooperation of HIPK2 and Sp100
      for the induction of p21(Waf1) is completely dependent on the presence of p53 and
      the kinase function of HIPK2. Downregulation of Sp100 levels by expression of
      siRNA does not interfere with p53-mediated transcription, but obviates the
      enhancing effect of HIPK2. In summary, these experiments reveal a novel function
      for Sp100 as a coactivator for HIPK2-mediated p53 activation.

PMID- 14647469
TI  - Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target.
AB  - The discovery of the p73 and p63 genes, homologous to p53 tumor suppressor has
      uncovered a family of transcription factors and widened the scenario of cell
      cycle control and apoptosis. We have identified a putative p53-responsive element
      in the human adenosine deaminase (ADA) gene, an important enzyme involved in
      nucleotide metabolism, the deficit of which causes the inhibition of DNA
      synthesis and repair. Here, we demonstrate that the ectopic expression of p73
      isoforms leads to the ADA gene upregulation, showing for the first time a
      correlation between p73 and ADA. We found that p73 promotes ADA gene expression
      following a dNTP unbalance generated by ADA enzyme deficiency and
      2'deoxyadenosine accumulation. The abrogation of p73 transcriptional activity by
      the specific dominant-negative p73DD abolishes ADA induction. By contrast, the
      ADA gene does not appear to be a functional p53 target in the physiological
      conditions we tested. On the whole, our results contribute to the emerging
      picture that p73 could play a different role from p53 in normal growth and
      development by inducing alternative target genes, which are not shared by p53.

PMID- 14647470
TI  - Constitutive DNA damage is linked to DNA replication abnormalities in Bloom's
      syndrome cells.
AB  - Bloom's syndrome (BS) is an autosomal recessive disorder associated with an
      elevated incidence of cancers. The gene mutated in BS, BLM, encodes a RecQ
      helicase family member. BS cells exhibit genomic instability, including excessive
      homologous recombination and chromosomal aberrations. We reported previously that
      BS cells also demonstrate increased error-prone nonhomologous endjoining, which
      could contribute to genomic instability in these cells. Here, we show that BS
      cells display an abnormality in the timing of replication of both early
      replicating genes and late-replicating loci such as chromosomal fragile sites.
      This delayed replication is associated with a constitutively increased frequency
      of sites of DNA damage and repair, as determined by the presence of DNA repair
      factors such as RAD51 and Ku86. In addition, another RecQ family helicase, WRN,
      also localizes to these repair sites. The presence of these repair sites
      correlates with the temporal appearance of cyclin B1 expression, indicative of
      the cells having progressed beyond mid-S phase in the cell division cycle.
      Critically, these defects in BS cells are the direct result of loss of BLM
      function, because BS cells phenotypically 'reverted' following transfection with
      the BLM cDNA no longer show such defects. Thus, our data indicate that
      constitutive DNA damage is coupled to delayed DNA replication in BS cells.

PMID- 14647471
TI  - Bcl-2 and Bcl-x(L) differentially protect human prostate cancer cells from
      induction of apoptosis by melanoma differentiation associated gene-7, mda-7/IL
      24.
AB  - Subtraction hybridization identified melanoma differentiation associated gene-7,
      mda-7, in the context of terminally differentiated human melanoma cells. Based on
      its structure, cytokine-like properties and proposed mode of action, mda-7 has
      now been classified as IL-24. When expressed by means of a replication
      incompetent adenovirus, Ad.mda-7 induces apoptosis in a broad range of cancer
      cells, without inducing harmful effects in normal fibroblast or epithelial cells.
      These unique properties of mda-7/IL-24 suggest that this gene will prove
      beneficial for cancer gene therapy. We now demonstrate that Ad.mda-7 decreases
      viability by induction of apoptosis in hormone-responsive (LNCaP) and hormone
      independent (DU-145 and PC-3) human prostate carcinomas, without altering growth
      or survival in early-passage normal human prostate epithelial cells (HuPEC).
      Ad.mda-7 causes G(2)/M arrest and apoptosis in LNCaP (p53-wildtype), DU-145 (p53
      mutant, Bax-negative) and PC-3 (p53-negative) prostate carcinomas, but not in
      HuPEC. Apoptosis induction correlated with changes in the ratio of pro- to
      antiapoptotic Bcl-2 protein family members. A potential functional role for
      changes in bcl-2 family gene expression in Ad.mda-7-induced apoptosis was
      suggested by the finding that forced overexpression of bcl-x(L) or bcl-2
      differentially diminished the apoptotic effect of Ad.mda-7 in prostate
      carcinomas. These results confirm that induction of apoptosis by the mda-7/IL-24
      gene in prostate cancer cells is Bax- and p53-independent and is mediated by
      mitochondrial pathways involving bcl-2 family gene members. The mda-7/IL-24 gene
      represents a new class of cancer-specific apoptosis-inducing genes with obvious
      potential for the targeted gene-based therapy of human prostate cancer.

PMID- 14647472
TI  - Acidic substitution of the activation loop tyrosines in TrkA supports nerve
      growth factor-dependent, but not nerve growth factor-independent, differentiation
      and cell cycle arrest in the human neuroblastoma cell line, SY5Y.
AB  - TrkA is the receptor tyrosine kinase (RTK) for nerve growth factor (NGF) and
      stimulates NGF-dependent cell survival and differentiation in primary neurons and
      also differentiation of neuroblastomas and apoptosis of medulloblastomas. We have
      previously shown that aspartic acid and glutamic acid substitution (AspGlu and
      GluAsp) of the activation loop tyrosines in TrkA (Tyr(683) and Tyr(684)) supports
      NGF-independent neuritogenesis and cell survival in PC12 cell-derived nnr5 cells.
      In this study, the AspGlu and GluAsp mutant Trks have been analysed for their
      ability to support NGF-independent and NGF-dependent neuritogenesis,
      proliferation and cell signalling in the human neuroblastoma cell line, SY5Y. We
      find that the AspGlu and GluAsp mutant Trks support NGF-dependent, but not NGF
      independent, autophosphorylation, neuritogenic responses and/or inhibit cell
      cycle progression. The NGF-dependent neuritogenic responses are lower for the
      mutant Trks (approximately 30-60% for AspGlu and 50-60% for GluAsp), relative to
      wild-type TrkA. While both the AspGlu and GluAsp mutant Trks support NGF
      dependent transient phosphorylation of Shc, PLCgamma-1, AKT, FRS2, SH2B as well
      as prolonged MAP kinase activation, the GluAsp mutant induces stronger NGF
      dependent tyrosine phosphorylation of FRS2 and SH2B, as well as a stronger
      reduction in bromodeoxyuridine (BrdU) incorporation. Collectively, these data
      suggest that neither absolute levels of receptor autophosphorylation, high levels
      of TrkA expression nor the activation of a specific signalling pathway is
      dominant and absolutely essential for neuritogenesis and cell cycle arrest of
      SY5Y cells.

PMID- 14647473
TI  - Evidence for radiosensitizing by gliotoxin in HL-60 cells: implications for a
      role of NF-kappaB independent mechanisms.
AB  - Radioresistance markedly impairs the efficacy of tumor radiotherapy and may
      involve antiapoptotic signal transduction pathways that prevent radiation-induced
      cell death. A common cellular response to genotoxic stress induced by radiation
      is the activation of the nuclear factor kappa B (NF-kappaB). NF-kappaB activation
      in turn can lead to an inhibition of radiation-induced apoptotic cell death.
      Thus, inhibition of NF-kappaB activation is commonly regarded as an important
      strategy to abolish radioresistance. Among other compounds, the fungal metabolite
      gliotoxin (GT) has been reported to be a highly selective inhibitor of NF-kappaB
      activation. Indeed, low doses of GT were sufficient to significantly enhance
      radiation-induced apoptosis in HL-60 cells. However, this effect turned out to be
      largely independent of NF-kappaB activation since radiation of HL-60 cells with
      clinically relevant doses of radiation induced only a marginal increase in NF
      kappaB activity, and selective inhibition of NF-kappaB by SN50 did not result in
      a marked enhancement of GT-induced apoptosis. GT induced activation of JNKs,
      cytochrome c release from the mitochondria and potently stimulated the caspase
      cascade inducing cleavage of caspases -9, -8, -7 and -3. Furthermore, cleavage of
      the antiapoptotic protein X-linked IAP and downregulation of the G2/M-specific
      IAP-family member survivin were observed during GT-induced apoptosis. Finally,
      the radiation-induced G2/M arrest was markedly reduced in GT-treated cells most
      likely due to the rapid induction of apoptosis. Our data demonstrate that various
      other pathways apart from the NF-kappaB signaling complex can sensitize tumor
      cells to radiation and propose a novel mechanism for radiosensitization by GT,
      the interference with the G2/M checkpoint that is important for repair of
      radiation-induced DNA damage in p53-deficient tumor cells.

PMID- 14647474
TI  - Biologic sequelae of c-Jun NH(2)-terminal kinase (JNK) activation in multiple
      myeloma cell lines.
AB  - Although c-Jun NH(2)-terminal kinase (JNK) is activated by treatment with
      therapeutic agents, the biologic sequelae of inhibiting constitutive activation
      of JNK has not yet been clarified. In this study, we examine the biologic effect
      of JNK inhibition in multiple myeloma (MM) cell lines. JNK-specific inhibitor
      SP600125 induces growth inhibition via induction of G1 or G2/M arrest in U266 and
      MM.1S multiple myeloma cell lines, respectively. Neither exogenous IL-6 nor
      insulin-like growth factor-1 (IGF-1) overcome SP600125-induced growth inhibition,
      and IL-6 enhances SP600125-induced G2/M phase in MM.1S cells. Induction of growth
      arrest is mediated by upregulation of p27(Kip1), without alteration of p53 and
      JNK protein expression. Importantly, SP600125 inhibits growth of MM cells
      adherent to bone marrow stromal cells (BMSCs). SP600125 induces NF-kappaB
      activation in a dose-dependent fashion, associated with phosphorylation of
      IkappaB kinase alpha (IKKalpha) and degradation of IkappaBalpha. In contrast,
      SP600125 does not affect phosphorylation of STAT3, Akt, and/or ERK. IKK-specific
      inhibitor PS-1145 inhibits SP600125-induced NF-kappaB activation and blocks the
      protective effect of SP600125 against apoptosis. Our data therefore demonstrate
      for the first time that inhibiting JNK activity induces growth arrest and
      activates NF-kappaB in MM cells.

PMID- 14647475
TI  - Human CD8(+) T-cell differentiation in response to viruses.

PMID- 14647476
TI  - CD28-mediated co-stimulation: a quantitative support for TCR signalling.

PMID- 14647477
TI  - Making sense of mass destruction: quantitating MHC class I antigen presentation.

PMID- 14647478
TI  - The mechanisms of immune diversification and their disorders.

PMID- 14647479
TI  - T-cell-antigen recognition and the immunological synapse.

PMID- 14647480
TI  - Dendritic-cell control of pathogen-driven T-cell polarization.

PMID- 14647481
TI  - Taking our breath away: dendritic cells in the pathogenesis of asthma.

PMID- 14647482
TI  - The delta-opioid receptor agonist (+)BW373U86 regulates BDNF mRNA expression in
      rats.
AB  - delta-Opioid receptor agonists have antidepressant-like effects in behavioral
      models of depression. Chronic administration of classical antidepressants
      upregulates mRNA expression of brain-derived neurotrophic factor (BDNF) and its
      high-affinity tyrosine kinase receptor, TrkB in the frontal cortex and
      hippocampus of rats. Increases in BDNF and TrkB levels are thought to be
      important for the therapeutic effects of these drugs. Therefore, we examined the
      ability of the delta-opioid receptor agonist (+)BW373U86 to regulate BDNF and
      TrkB mRNA expression in frontal cortex, hippocampus, as well as, basolateral
      amygdala, endopiriform nucleus, and primary olfactory cortex. At 3 h after a
      single administration of (+)BW373U86 animals were killed and BDNF and TrkB mRNA
      levels were examined by in situ hybridization. BDNF mRNA levels produced by
      (+)BW373U86 were compared to acute administration of the antidepressants
      desipramine and bupropion. A behaviorally antidepressant dose of 10 mg/kg
      (+)BW373U86 increased BDNF mRNA expression in all regions examined; a smaller
      dose of (+)BW373U86 (1 mg/kg) significantly increased BDNF mRNA expression only
      in frontal cortex. The delta-opioid receptor antagonist naltrindole blocked
      (+)BW373U86-mediated increases in BDNF mRNA expression. In addition, tolerance
      developed to increased BDNF mRNA expression with repeated injection, except in
      frontal cortex. Midazolam was administered to some animals to prevent the
      convulsions produced by (+)BW373U86, but midazolam did not block delta-opioid
      receptor-mediated increases in BDNF mRNA expression in frontal cortex,
      hippocampus, or amygdala. Unlike desipramine and bupropion, (+)BW373U86
      upregulated BDNF mRNA expression acutely (within 3 h after a single
      administration). These data support the concept that delta-opioid receptor
      agonists may have antidepressant potential, and could be good targets for the
      development of faster-acting antidepressants.

PMID- 14647483
TI  - ATF2, a member of the CREB/ATF family of transcription factors, in chronic stress
      and consequent to antidepressant treatment: animal models and human post-mortem
      brains.
AB  - The regulation of gene expression has been implicated in the etiology and
      treatment of depression. Transcription factors serve as the intermediates between
      intracellular cascades and gene expression, and may therefore be involved in the
      pathophysiology and pharmacotherapy of depression. We and others have previously
      reported an increase in the phosphorylation of the transcription factor cAMP
      response element binding protein (CREB) by antidepressants, alongside brain
      region-specific alterations in pCREB by stress. In the present study, we examined
      the expression of another member of the CREB/ATF family of transcription factors,
      ATF2, in the brains of rats chronically treated with two different
      antidepressants, and in rats 4 months after their exposure to prolonged stress.
      ATF2 phosphorylation was decreased by antidepressants and increased at the
      aftermath of prolonged stress, specifically in the frontal cortex. We also
      examined ATF2 expression in the ventral parieto-occipital region of post-mortem
      human brains of normal controls, depressed, bipolar, and schizophrenic patients,
      obtained from the Stanley Foundation Brain Consortium. No alterations were
      observed in the levels of ATF2. However, in the depressed group, the pATF2 levels
      were higher in unmedicated compared to medicated patients, suggesting an
      antidepressant-induced reduction in pATF2. We discuss the possible role of ATF2
      in depression, and propose that an interplay between ATF2 and CREB, and possibly
      other transcription factors, determines the final gene expression pattern in the
      etiology and treatment of depression.

PMID- 14647485
TI  - Acute cortisol administration promotes sleep intensity in man.
AB  - The neuronal mechanisms of sleep generation, in particular synchronization of
      brain activity in the process of non-rapid-eye movement (non-REM) sleep, has been
      elucidated in the past decade. A previous study of our group showed that acute
      administration of cortisol is known to increase slow-wave sleep and suppress
      rapid-eye movement (REM) sleep in man. To further elucidate the non-REM sleep
      promoting effects of cortisol with respect to the synchronization of cortical
      activity, it is important to establish a sleep-state-specific quantitative EEG
      analysis. We therefore investigated the effects of repetitive injections of
      hydrocortisone on spectral composition of sleep EEG in 10 healthy male young
      volunteers. In addition, we performed high-frequency blood samplings to assess
      the relation between changes in the sleep EEG and sleep-associated secretion of
      growth hormone (GH). Cortisol administration resulted in a significant increase
      in highly synchronized EEG activity including delta and theta frequencies,
      according to a higher amount of slow-wave sleep. This effect predominated in the
      first few hours of night sleep. REM sleep was decreased, which appeared to be
      secondary to the lengthened first sleep cycle. The cortisol-induced stimulation
      of GH release did not occur in correspondence with the increased slow-wave
      activity. In view of the sleep impairing properties of corticotropin-releasing
      hormone (CRH) and the sleep-promoting function of GH-releasing hormone, it
      appears likely that a negative feedback inhibition of endogenous CRH was the key
      mechanism mediating the observed results. The cortisol-induced effects on sleep
      intensity and sleep-associated GH secretion appeared to be driven by different
      mechanisms.

PMID- 14647484
TI  - Profound impairment in social recognition and reduction in anxiety-like behavior
      in vasopressin V1a receptor knockout mice.
AB  - Considerable evidence suggests that arginine vasopressin (AVP) is critically
      involved in the regulation of many social and nonsocial behaviors, including
      emotionality. The existence of two AVP receptors in the brain, namely the V1a and
      V1b subtypes, and the lack of clear pharmacological data using selective agonists
      or antagonists, make it difficult to determine which receptor is responsible for
      the AVP-mediated effects on behavior. Here we report the behavioral effects of a
      null mutation in the V1a receptor (V1aR) in male mice. Male mice lacking
      functional V1aR (V1aRKO) exhibit markedly reduced anxiety-like behavior and a
      profound impairment in social recognition. V1aRKO performed normally on spatial
      and nonsocial olfactory learning and memory tasks. Acute central administration
      of AVP robustly stimulated stereotypical scratching and autogrooming in wild-type
      (WT), but not V1aRKO males. AVP and oxytocin (OT) mRNA and OT receptor-binding
      levels were similar in WT and V1aRKO mice. Given the current findings, the V1aR
      may provide a novel potential pharmacological target for social and affective
      disorders including autism, and anxiety disorders.

PMID- 14647486
TI  - Encoding crystal microstructure and chain folding in the chemical structure of
      synthetic polymers.
AB  - The development of robust methodologies to control the solid-state structure of
      polymeric materials by appropriate design of the macromolecular architecture has
      a crucial impact on the mechanical properties of these materials. Here, we
      demonstrate the feasibility of controlling chain folding of polymers by steric
      interactions only, in contrast to previous attempts aimed at engineering polymer
      crystallization through hydrogen bonding. In a linear synthetic macromolecule
      similar to polyethylene, we encoded structural instructions that are translated
      during a crystallization process to generate a unique, semi-crystalline
      morphology with structure-controlled crystal thickness of approximately 5 nm that
      remains constant over a wide temperature range. The molecular code consists of a
      linear backbone alternating crystallizable, long alkyl sequences of monodisperse
      sizes separated by short spacers containing side-chains and acting as stops and
      fold-controlling units. This simple strategy could be used to produce advanced
      polymeric materials with fine control of the crystalline and amorphous regions.

PMID- 14647487
TI  - Accelerating access.

PMID- 14647489
TI  - Nature materials: Velcro mechanics in wood.

PMID- 14647490
TI  - Photonic crystals: cavities without leaks.

PMID- 14647491
TI  - Surface diffusion: shifting strings.

PMID- 14647492
TI  - Inorganic chemistry: Traps for cations.

PMID- 14647493
TI  - Material witness: Towards a materials ecology.

PMID- 14647496
TI  - Homeostatic proliferation is a barrier to transplantation tolerance.
AB  - Despite the ease of inhibiting immune responses by blockade of T-cell
      costimulation in naive rodent models, it is difficult to suppress those responses
      in animals with memory cells. Studies demonstrating the importance of
      alloreactive T-cell deletion during tolerance induction have promoted use of
      peritransplant T-cell-depleting therapies in clinical trials. But potentially
      complicating wide-scale, nonspecific T-cell depletion is the finding that
      extensive T-cell proliferation can occur under conditions of lymphopenia. This
      process, termed homeostatic proliferation, may induce acquisition of functional
      memory T cells. Here, using clinically relevant mouse models of peripheral T-cell
      depletion, we show that residual nondepleted T cells undergo substantial
      homeostatic expansion. In this setting, costimulatory blockade neither
      significantly suppresses homeostatic proliferation nor prevents allograft
      rejection. In addition, T cells that have completed homeostatic proliferation
      show dominant resistance to tolerance when adoptively transferred into wild-type
      recipients, consistent with known properties of memory cells in vivo. These
      findings establish the importance of homeostatic proliferation in clinically
      relevant settings, demonstrate the barrier that homeostatic proliferation can
      present to the induction of transplantation tolerance, and have important
      implications for transplantation protocols that use partial or complete
      peripheral T-cell depletion.

PMID- 14647498
TI  - Opportunity knocks.

PMID- 14647497
TI  - Modifying quinolone antibiotics yields new anxiolytics.
AB  - Patients taking fluoroquinolone antibiotics such as norfloxacin exhibit a low
      incidence of convulsions and anxiety. These side effects probably result from
      antagonism of the neurotransmitter gamma-aminobutyric acid (GABA) at the brain
      GABA(A) receptor complex (GRC). Modification of norfloxacin yields molecules such
      as compound 4 that potentiate GABA action with alpha(2) subunit selectivity.
      Compound 4 is anxiolytic but does not cause sedation, and may represent a new
      class of ligands that have anxiolytic activity without sedative liability.

PMID- 14647499
TI  - Erythropoietin may impair, not improve, cancer survival.

PMID- 14647502
TI  - SARS spreads new outlook on quarantine models.

PMID- 14647504
TI  - Strain of unknown prions weighs heavily on Japan, Italy.

PMID- 14647506
TI  - IBM accused of ignoring employee 'cancer cluster'.

PMID- 14647510
TI  - Inhibition of platelet thromboxane receptor function by a thrombin receptor
      targeted pepducin.

PMID- 14647513
TI  - Antiretroviral treatment for HIV infection in developing countries: an attainable
      new paradigm.

PMID- 14647516
TI  - Dilated cardiomyopathy: learning to live with yourself.

PMID- 14647517
TI  - Anti-steroid takes aim at neuropathy.

PMID- 14647518
TI  - JAKing up immunosuppression.

PMID- 14647519
TI  - Ion implicated in blood pact.

PMID- 14647520
TI  - Marrow to muscle, fission versus fusion.

PMID- 14647521
TI  - Prion disease: bridging the spleen-nerve gap.

PMID- 14647522
TI  - Parade of prions.

PMID- 14647523
TI  - Autoimmunity heats up.

PMID- 14647524
TI  - Push me, pull you.

PMID- 14647527
TI  - The promises and pitfalls of reboxetine.
AB  - The antidepressant compound, morpholine, 2-[(2-ethoxyphenoxy)phenylmethyl]
      ,methanesulfonate, or reboxetine, is a selective noradrenergic reuptake inhibitor
      that acts by binding to the norepinephrine (NE) transporter and blocking reuptake
      of extracellular NE back into terminals. This compound has low affinity for other
      transporters and receptors. The development of reboxetine as a potential
      antidepressant stems from the prior demonstration that blockade of the NE
      transporter imparts antidepressant activity. Desipramine, lofepramine, and
      nortryptiline are examples of tricyclic antidepressant (TCA) compounds from the
      first generation of antidepressants that exert their effects by blockade of NE
      reuptake. Maprotiline, a non-tricyclic compound, is also a NE selective reuptake
      inhibitor. Unfortunately, these antidepressants are also associated with
      interactions with muscarinic, histaminergic, and adrenergic receptors, which are
      known to contribute to a variety of untoward side effects. Despite the positive
      pharmacological profile of reboxetine, i.e., selectivity and specificity, with
      relatively fewer side effects, its use as an antidepressant is currently limited
      to Europe. Reboxetine is marketed as Edronax in the UK, Norebox in Italy, and as
      Irenor in Spain. It is registered in Germany, Sweden, Denmark, Ireland, Austria
      and Finland. Based on studies conducted primarily outside the US, the FDA granted
      a preliminary letter of approval in 1999. However, more recent clinical studies
      conducted in the US and Canada, prompted by the FDA, resulted in a letter of non
      approval. To date, it is unclear why the further development of reboxetine as an
      antidepressant in the US has been halted. Despite this setback, reboxetine has
      been a valuable pharmacological tool to assess the role of the noradrenergic
      system in preclinical studies of depressive disorder.

PMID- 14647528
TI  - BAY 38-7271: a novel highly selective and highly potent cannabinoid receptor
      agonist for the treatment of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is the most common cause of mortality and morbidity
      in adults under 40 years of age in industrialized countries. Worldwide the
      incidence is increasing, about 9.5 million people are hospitalized per year due
      to TBI, and the death rate is estimated to be more than one million people per
      year. Recently BAY 38-7271 has been characterized as a structurally novel,
      selective and highly potent cannabinoid CB1/CB2 receptor agonist in vitro and in
      vivo with pronounced neuroprotective efficacy in a rat traumatic brain injury
      model, showing a therapeutic window of at least 5 h. Furthermore, neuroprotective
      efficacy was also found in models of transient and permanent occlusion of the
      middle cerebral artery and brain edema models as well. In this article we review
      the in vitro and in vivo pharmacology of BAY 38-7271, the results from acute and
      subacute toxicity studies, pharmacokinetics and drug metabolism in animals and
      healthy male volunteers. In phase I studies BAY 38-7271 was safe and well
      tolerated when administered by i.v. infusion for either 1 or 24 h. As the doses
      of BAY 38-7271 in animals needed for maximal neuroprotective efficacy were
      significantly lower than those inducing typical cannabinoid-like side effects, it
      is to be expected that the compound will offer a novel therapeutic approach with
      a favorable therapeutic window for the treatment of TBI or cerebral ischemia.

PMID- 14647529
TI  - Pharmacology of acamprosate: an overview.
AB  - In the last years important advances have been made in the development of drugs
      for the treatment of alcohol addiction. Acamprosate (calcium bis
      acetylhomotaurine) is one of the better established drugs in this field on the
      European market. This review focuses first on the pharmacokinetics of
      acamprosate. The published data and the recent advances in our knowledge on the
      mechanisms involved in the intestinal absorption and elimination of this drug are
      summarized. The importance of pharmacokinetics for the proper clinical use of
      acamprosate is highlighted. The anti-relapse as well as the well-known effects of
      acamprosate on ethanol intake are discussed. The recent experiments in animal
      models of conditioned withdrawal are reviewed. These experiments, explored for
      the first time the anticraving effect of the drug. Finally, the proposed
      hypotheses on the neuropharmacological mechanism of action of acamprosate are
      discussed. The discussion deals with the relative importance of various
      hypotheses as well as with the recent experiments that support them. It is
      pointed out that further research is necessary in order to clearly understand the
      mode of action of acamprosate as well as the neurobiological mechanisms involved
      in alcohol dependence.

PMID- 14647530
TI  - Neuropharmacological profile of an atypical antipsychotic, NRA0562.
AB  - Schizophrenia is a serious and disabling psychiatric disorder affecting
      approximately 1% of the world's population. A new generation of atypical
      antipsychotics has been introduced over the past decade. These atypical
      antipsychotics have comparable or greater efficacy than traditional
      antipsychotics in the treatment of the psychotic symptoms of schizophrenia and a
      much improved neurologic side effect profile. This paper reviews the
      pharmacological efficacy and safety of a potential atypical antipsychotic,
      NRA0562. NRA0562 has a high affinity for dopamine D1, D2L, D4.2, 5-HT2A receptors
      as well as alpha1-adrenoceptors, and has a moderate affinity for H1 receptors.
      NRA0562 strongly binds to 5-HT2A receptors and alpha1-adrenoceptors in the
      frontal cortex, its binding to striatal D2 receptors is weaker, similar to that
      of clozapine. NRA562 displayed potent antipsychotic activities in animal models
      of schizophrenia, such as methamphetamine (MAP)-induced hyperactivity,
      apomorphine-induced disruption of pre-pulse inhibition and conditioned avoidance
      test. NRA0562 is more potent in reversing the inhibitory effects of MAP at A10
      than at A9 dopamine neurons. It increased Fos-like immunoreactivity in the
      nucleus accumbens more effectively than in the dorsolateral striatum, indicating
      that NRA0562 has the profile of an atypical antipsychotic. In vivo assays for
      extrapyramidal side effect liability showed that NRA0562 has a low rate of
      neurological side effects. Thus, NRA0562 may have unique antipsychotic activity
      with a lower propensity for extrapyramidal side effects.

PMID- 14647531
TI  - Pharmacology of KB-R7943: a Na+-Ca2+ exchange inhibitor.
AB  - The Na+-Ca2+ exchange (NCX) system plays a pivotal role in regulating
      intracellular Ca2+ concentration in cardiomyocytes, neuronal cells, kidney and a
      variety of other cells. It performs a particularly important function in
      regulating cardiac contractility and electrical activity. One of the leading NCX
      inhibitors is KB-R9743 (KBR) that appears to exhibit selectivity for Ca2+-influx
      mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology
      of KBR and provide a brief summary of studies with other NCX inhibitors, such as
      SEA0400 (SEA) and SN-6 (SN). Potential clinical usefulness of KBR and other NCX
      inhibitors is still controversial but the reviewed findings may be helpful in
      designing more selective and clinically useful NCX inhibitors for the treatment
      of cardiac, neuronal and kidney diseases.

PMID- 14647532
TI  - CVT-510: a selective A1 adenosine receptor agonist.
AB  - Adenosine is an endogenous nucleoside that has potent antiarrhythmic effects on
      paroxysmal supraventricular tachycardia (PSVT) due to its negative dromotropic
      effects on the atrioventricular node. In addition to its electrophysiologic
      effects, adenosine has important effects on vascular smooth muscle cells,
      inflammatory cells, the central nervous system, and the kidney. Four known
      adenosine receptor subtypes (A1, A2A, A2B, and A3) mediate the pleiotropic
      effects of adenosine in humans. These receptors are coupled to a wide range of
      second messenger cascades. Activation of the A1 adenosine receptor accounts for
      the negative chronotropic and dromotropic effects of adenosine, whereas A2A, A2B
      and A3 adenosine receptor activation are responsible for such effects as coronary
      vasodilation, bronchospasm, inhibition of platelet aggregation, and neuronal
      stimulation. Elucidation of the specific properties of each of the adenosine
      receptor subtypes has led to the development of selective ligands as potential
      therapeutic agents. CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside,
      was developed as a selective A1 adenosine receptor agonist that specifically
      targets the atrioventricular node for termination of PSVT. Preliminary clinical
      trials have shown that CVT-510 is effective in terminating PSVT and eliminating
      many of the undesirable adverse effects of adenosine. CVT-510 is also being
      explored as a potential agent for controlling the ventricular rate of atrial
      fibrillation and flutter.

PMID- 14647533
TI  - Ezetimibe: a first-in-class, novel cholesterol absorption inhibitor.
AB  - Significant numbers of patients at risk for coronary heart disease (CHD) fail to
      reach National Cholesterol Education Program (NCEP)-designated low density
      lipoprotein cholesterol (LDL-C) goals in spite of the wide range of currently
      available treatments, including combination therapies. Ezetimibe, the first in a
      class of novel cholesterol absorption inhibitors, demonstrated lipid-lowering and
      antiatherosclerotic activity in experimental and clinical hypercholesterolemia.
      Studies in hypercholesterolemic dogs showed that ezetimibe coadministered with
      statins caused greater lipid-lowering effects compared to either drug alone.
      These effects were confirmed in clinical studies of patients with primary
      hypercholesterolemia where initiation of treatment with ezetimibe plus a statin,
      or addition of ezetimibe to ongoing statin therapy, produced significant
      incremental reductions in LDL-C, as well as incremental increases in high-density
      lipoprotein cholesterol (HDL-C) and reductions in triglyceride levels.
      Combination therapy also significantly increased the number of patients attaining
      LDL-C goal at the end of treatment, compared to statin monotherapy. In studies
      using simvastatin, atorvastatin, pravastatin, and lovastatin, addition of
      ezetimibe to low dose statin was as effective as a 2- to 3-fold upward titration
      of the corresponding statin dose. Ezetimibe-statin combination therapy provided
      similar improvements in patients with primary hypercholesterolemia, as well as
      with heterozygous and homozygous familial hypercholesterolemia. Ezetimibe
      monotherapy effectively reduced plasma campesterol and sitosterol in patients
      with homozygous sitosterolemia. Clinical studies showed that ezetimibe was well
      tolerated, with a safety profile comparable to placebo when administered as
      monotherapy and comparable to statin alone when coadministered with a statin.
      These data provide strong evidence that, through their complementary lipid
      lowering mechanisms, ezetimibe coadministered with a statin offers an effective
      combination treatment option for patients with hypercholesterolemia, including
      those with genetically inherited disease.

PMID- 14647534
TI  - RWJ-58259: a selective antagonist of protease activated receptor-1.
AB  - Protease activated receptor-1 (PAR-1) is a key mediator of the cellular actions
      of alpha-thrombin. Thus, antagonism of this unique G-protein coupled receptor
      with a small molecule represents a means of selectively inhibiting thrombin's
      cellular actions without inhibiting its proteolytic activity. RWJ-58259 (alphaS)
      N-[(1S)-3-amino-1-[[(phenylmethyl)- amino]carbonyl]propyl]-alpha-[[[[[1-(2,6
      dichlorophenyl)methyl]-3-(1-pyrrolidinylmethyl)-1H-indazol-6
      yl]amino]carbonyl]amino]-3,4-difluorobenzenepropanamide) is a potent and
      selective inhibitor of PAR-1 identified as part of a synthetic chemistry program
      based upon a de novo design approach. RWJ-58259 inhibited thrombin-induced
      platelet aggregation in human platelets with an IC50 of 0.37 microM without
      inhibiting thrombin's proteolytic activity or aggregation induced by other
      agonists. RWJ-58259 was not effective in guinea pig models of thrombosis. This
      reflected the presence of a second thrombin-sensitive receptor system in guinea
      pigs (PAR-3/4) and the selectivity of RWJ-58259 for PAR-1. However, RWJ-58259 was
      effective in a non-human primate model of thrombosis. Because human platelets
      have a PAR expression profile similar to the non-human primate, PAR-1 antagonism
      has the potential to be antithrombotic in humans. RWJ-58259 also inhibited
      thrombin-induced intracellular calcium signaling and proliferation in rat
      vascular smooth muscle cells. Perivascular application of RWJ-58259 in vivo
      significantly inhibited arterial injury-induced stenosis in a rat model of
      balloon angioplasty. These preclinical results suggest a potential clinical
      utility of RWJ-58259 for treatment of thrombotic disorders and vascular injury
      associated with acute coronary interventions and atherosclerosis. Given the
      potential role of PAR-1 in thrombin's actions in other cell types and disease
      states, RWJ-58259 provides a means for assessing additional clinical utilities of
      PAR-1 antagonism in disease conditions such as inflammation, cancer and
      neurodegeneration.

PMID- 14647535
TI  - Stem cell therapy in ischemic heart disease.
AB  - Coronary artery disease (CAD) remains the leading cause of death in the Western
      world. The high impact of its main sequelae, acute myocardial infarction and
      congestive heart failure (CHF), on the quality of life of patients and the cost
      of health care drives the search for new therapies. The recent finding that stem
      cells contribute to neovascularization and possibly improve cardiac function
      after myocardial infarction makes stem cell therapy the most highly active
      research area in cardiology. Although the concept of stem cell therapy may
      revolutionize heart failure treatment, several obstacles need to be addressed. To
      name a few: 1) Which patient population should be considered for stem cell
      therapy? 2) What type of stem cell should be used? 3) What is the best route for
      cell delivery? 4) What is the optimum number of cells that should be used to
      achieve functional effects? 5) Is stem cell therapy safer and more effective than
      conventional therapies? The published studies vary significantly in design,
      making it difficult to draw conclusions on the efficacy of this treatment. For
      example, different models of ischemia, species of donors and recipients,
      techniques of cell delivery, cell types, cell numbers and timing of the
      experiments have been used. However, these studies highlight the landmark concept
      that stem cell therapy may play a major role in treating cardiovascular diseases
      in the near future. It should be noted that stem cell therapy is not limited to
      the treatment of ischemic cardiac disease. Non-ischemic cardiomyopathy,
      peripheral vascular disease, and aging may be treated by stem cells. Stem cells
      could be used as vehicle for gene therapy and eliminate the use of viral vectors.
      Finally, stem cell therapy may be combined with pharmacological, surgical, and
      interventional therapy to improve outcome. Here we attempt a systematic overview
      of the science of stem cells and their effects when transplanted into ischemic
      myocardium.

PMID- 14647536
TI  - Tumor cell-collagen interactions: Identification and semi-quantitative evaluation
      of selectively-expressed genes by combination of differential display- and
      multiplex-PCR.
AB  - It is widely acknowledged that the presence of extracellular matrix components as
      substrates can drastically modulate the phenotype and gene expression of cultured
      cells, including tumor cells. A number of published reports indicated that
      substrates made from two peculiar collagen species, i.e. type V and OF/LB, which
      are abnormally deposited in the stroma of primary ductal infiltrating carcinoma
      (d.i.c.) of the breast "in vivo," were able to exert marked and opposite effects
      on "in vitro" viability, growth and invasiveness of the 8701-BC cell line,
      isolated from d.i.c.-affected breast epithelium. To complement such functional
      data on the effect of cell-collagen interactions with information at molecular
      level, we have utilized a combination of differential display- and semi
      quantitative multiplex-PCR techniques with the aim of detecting variations in the
      expression levels of selected genes by cells maintained in either culture
      condition. Here we report some prototypical data on the identification and semi
      quantitation of three of the differentially-amplified PCR products found, i.e.
      HSP2A and MSF-B which are up-regulated in cells grown onto OF/LB collagen
      substrate, and SRCAP which is prominently down-regulated in the presence of type
      V collagen substrate. This protocol represents a powerful tool for evaluating
      changes in the levels and patterns of gene expression which can be theoretically
      adapted to any experimental model system.

PMID- 14647537
TI  - Rest: a qualitative exploration of the phenomenon.
AB  - The founders of occupational therapy perceived rest as one of the performance
      areas of the profession. They believed that an optimal balance between work, play
      and rest was crucial in obtaining maximal function and health. However, few
      occupational therapy theorists or researchers have explored the phenomenon. The
      authors explored the phenomenon of rest as reported in the literature and through
      a qualitative study. The results of the literature review showed that rest is
      differentiated from sleep; rest is equated with interrupting physical and mental
      activity resulting in a relaxed state. Rest can be achieved by listening to
      music, hypnosis, reading, walking and sitting quietly. In this exploratory study,
      seven individuals working at Tel Aviv University were interviewed regarding their
      definitions of rest. The results indicated that rest was defined as an activity
      that was personal, quiet and effortless, experienced alone or with friends, and
      helped in doing daily activities. It is concluded that there is a need for
      occupational therapists to explore further the phenomenon of rest as it relates
      to occupational performance, ergonomics and health maintenance. Examining the
      concept of rest is a challenge that involves returning to the theoretical origins
      of the profession.

PMID- 14647538
TI  - Occupational therapy and early intervention: a family-centred approach.
AB  - The purpose of this study was to identify factors that encourage or inhibit
      family-centred practice in the occupational therapy intervention process. A
      qualitative paradigm using grounded theory methodology was utilized to gather and
      analyse data. Participants included six families and four occupational
      therapists. Data analysis from the family interviews identified six categories:
      education, communication, relationship, parental roles, follow through, and
      scheduling. With further analysis two central themes of time and support were
      extracted from these categories. Analysis of the occupational therapists'
      interviews revealed six categories: education, communication, relationship,
      sibling/family participation, follow through, and empowerment. The central themes
      emerging from these categories are time and natural routine. The themes obtained
      from the families and occupational therapists were then compared and family
      individuality was identified as the core concept. Viewing families as a unique
      entity is necessary to assist occupational therapists in providing the most
      effective family-centred occupational therapy.

PMID- 14647539
TI  - Concepts in occupational therapy in relation to the ICF.
AB  - Occupational therapists need an acceptable terminology to describe a client's
      clinical performance. The language or terminology must be in harmony with common
      language in the health care system but also reflect occupational therapists'
      professional responsibility. The aim of this paper is to help clarify
      similarities and differences between concepts in occupational therapy and the
      International Classification of Functioning, Disability and Health (ICF). Two
      studies were completed in which items in the International Classification of
      Impairments, Disabilities and Handicaps (ICIDH-2) were compared with concepts
      from the Swedish version of the assessment of Motor and Process Skills (AMPS) and
      the Assessment of Communication and Interaction Skills (ACIS-S). An expert panel
      of occupational therapists served as raters and 33 clients with learning
      disabilities and mental health problems were assessed. The result showed that 12
      (60%) of the skills items from the ACIS-S were found to be equivalent to items in
      then ICIDH-2. In total, 41% (n = 23) of the items in the AMPS or ACIS-S have a
      correlation higher then 0.60 with the ICIDH-2. The classification can serve as a
      useful tool for occupational therapists and supports communication between
      professions, but is not sufficient as a professional language for occupational
      therapists. Further research is indicated to examine how the ICF can be applied
      in occupational therapy and its implications on clinical practice.

PMID- 14647540
TI  - Reliability and validity of the Canadian Occupational Performance Measure for
      clients with psychiatric disorders in Taiwan.
AB  - The purpose of the study was to examine the reliability and validity of the
      Canadian Occupational Performance Measure (COPM) in Taiwanese clients with
      psychiatric disorders. The COPM was translated into Mandarin and tested on 141
      Taiwanese clients. The average age of the clients was 35.6 years; 94% were
      diagnosed with schizophrenia. The results of the study showed that the test
      retest reliability of the COPM was r = 0.842. The COPM identified occupational
      performance problems that included self-care (37%), productivity (25%), and
      leisure occupations (20%). Fifty percent of the therapists were receptive in
      adapting the client-centred approach and applying the COPM in their clinical
      practice. It was concluded that the COPM can be applied reliably to Taiwanese
      clients. Furthermore, the COPM was valuable in identifying information related to
      occupational performance that could not be identified elsewhere. Since 50% of the
      therapists felt reluctant about the appropriateness of the client-centred
      approach in their culture, it was important to examine the gap between clients'
      judgements and actual performance, as well as to evaluate the feasibility of the
      client-centred concept in clinical practice. Finally, the concept of the client
      centred approach needs to be disseminated and communicated to the occupational
      therapy profession in order that the COPM can be adequately applied in mental
      health practice.

PMID- 14647541
TI  - Reducing anxiety by pre-operative education: make the future familiar.
AB  - Pre-operative education is widely used by occupational therapists all over the
      world to help patients prepare for their impending surgery and post-operative
      needs. The purpose of this research was to gain understanding of how the pre
      operative education process is beneficial in reducing anxiety for patients
      awaiting a total hip replacement provided in one National Health Service Trust in
      England. The participants in this study were a convenient sample of health care
      professionals who presented information on pre-operative education during a nine
      month data collection period, and a sample of patients who attended the
      programme. Data were collected from observing five pre-operative education
      programmes, 26 written patient evaluations, 16 interviews with seven presenters
      of the education, observation of three team meetings, 20 interviews with 10
      patients, and documentation pertaining to the programme. From the results it
      seems that patient education can reduce anxiety by making the unknown familiar.
      Such familiarity can be achieved in three ways by: providing an understanding of
      the experiences patients will encounter during and after surgery; giving an
      opportunity to meet the staff that will be caring for them; and familiarizing
      patients with the environments they will meet when in hospital. Major limitations
      of the study were not being able to control for researcher bias and not providing
      a standardized instrument to collect data. It is recommended that further
      research be carried out to understand the dynamics between patient education and
      the reduction of anxiety among patients undergoing hip replacements.

PMID- 14647542
TI  - [Epidemiological study of university students].
AB  - OBJECTIVE: to study prevalence rates of psychological distress among university
      students. METHOD: descriptive correlational research. Data gathered administering
      the brief version ( Argentine adaptation) of the Psychiatric Epidemiological
      Research Interview (PERI) to a sample of 1130 individuals studying at the
      University of Buenos Aires are presented. (Age Mean: 23 years old). RESULTS: 30 %
      of female students and 15 % of male ones can be considered at psychopathological
      RISK. Psychological symptoms of distress more frequently found are: anxiety,
      anger, irritability, violent attitudes or feelings. It can be said that 33% of
      female students and 19% of male ones express their wish to have a psychological
      interview with some professional of the University Health Center. Prevalence
      rates of distress are higher among participants who study Agronony, Philosophy
      and Literature and Medicine. CONCLUSION: data analyzed show the need to
      incorporate a psychophysical assessment of students matriculated in the
      University. Currently they pass only through a medical one. The University Health
      Center can provide preventive programmes as well as assistance and interventions
      related to rehabilitations.

PMID- 14647543
TI  - [Prevalence of serious mental pathology in the city of San Luis].
AB  - OBJECTIVE: This work includes part of the results of the first epidemiological
      research on mental health held at San Luis City, aimed to estimate adult
      prevalence rate of mental pathology on San Luis' adult population. It has also
      been considered the prevalent kind of disorders. In both cases, it has been taken
      into account five domains of independent variables, due to sociodemographic
      characteristics: sex, age, educational level, occupational level, and residence
      zone. METHODS: The methodology is based on the epidemiological descriptive and
      transversal model. The assessment instrument, the Millon Clinical Multiaxial
      Inventory-II, was administrated to a representative adult sample, designed by a
      probabilistic sample methodology. RESULTS: The clinical measurement of
      Personality Pathology Scales and Sever Clinical Syndromes Scales showed a
      prevalence rate of 25,69% of serious mental pathology in general population,
      which is higher in women, 27,13%; than in men, 24,19%. In accordance to
      independent variables, there is a higher prevalence in elderly people, although
      there is no correlation with the number of symptoms; there is a lower prevalence
      among people with more years of education, with a relative correlation with
      number of symptoms-; and some professions showed higher scores than others, also
      with a relative correlation with number of symptoms. Considering the kind of
      mental disorders, there was a high prevalence of paranoid disorder and of
      alucinatory disorder, both in the women and men's samples. CONCLUSIONS: Finally,
      we found that the prevalence rates of serious mental pathology in San Luis
      population are similar to those obtained by previous studies in Argentina.

PMID- 14647544
TI  - [Epidemiology of alcohol consumption in Argentina].
AB  - Wine production in Argentina left its mark in alcoholic drinks, placing it much
      closer to the socio cultural habits of the Mediterranean Europeans of the middle
      of the 20th century than to the Saxon peoples where the priority was consuming
      distilled drinks. During the last twenty years a very important economic
      investment accompanied the changes in the patterns of alcohol use, basically
      because of the incorporation of adolescent and preadolescent population into the
      alcoholic drinks market. If the traditional permissive standard, which accepted
      the enjoyment of alcohol, was modified in the elements of culture that tended to
      set limits to its excess, evolution has leaned towards a culture that extends
      tolerance to excess, frequently referred to as an uncontrolled state. It is a
      change, which weighs even heavier upon those who are more vulnerable. Up to now
      although this has been evident in educational and economic areas, it can also be
      supported by other new factors. Historically, the focus of social concern has
      concentrated on those cases with alcohol dependence, as exemplified by the
      abstinence syndrome. The cultural trivialization of 'non addictive' levels of
      consumption, is sustained only by social tolerance. Preventive strategies must
      establish a system of alarm signals that target early detection, and as a result
      prompt attention. The variety of methods within the field of rehabilitation, in
      contrast to the scarce development in the secondary level, offers a sign of
      considerable bias in health policies. This is true both in the design of
      preventive programmes as well as in the training and organisation of support
      resources.

PMID- 14647545
TI  - [A review of thirty years of activity of the Research Program in Psychiatric
      Epidemiology (PEPSI) of the CONICET].
AB  - This article summarizes the activity of the Programa de Investigaciones en
      Epidemiologia Psiquiatrica (PEPSI) (Research Program in Psychiatric Epidemiology)
      of the CONICET, directed for more than thirty years by Fernando Pages Larraya.
      After an anthropologic psychiatric experience done in the Gran Chaco Gualamba, by
      the end of the 60s, Pages Larraya and his team developed the theory of Cultural
      Isoidias, zones into which the country could be divided for epidemiologic
      studies. This article summarizes some of the principal lines of investigation of
      this program which departures from an initial study of the prevalence of mental
      diseases in Argentina. Other lines of research (such as a study about
      marginality, about Alzheimer's disease, about alcoholism and about AIDS) are
      summarized very briefly so as to give the reader an idea about the enormous field
      of study embraced by the PEPSI.

PMID- 14647546
TI  - [Violent causes of death in young people of 10 to 24 years old. Argentina 1991 -
      2000].
AB  - OBJECTIVE: to study the most frequent death causes between young people during
      1991 to 2000. We worked at the Epidemiological Research Center of the Buenos
      Aires Academy of Medicine, with all the country's death dates certified by the
      Ministry of Health. Argentine young population (10 to 24 years old) was of about
      10,000,000 people, after the increase of 15% during the studied period. MATERIAL
      AND METHODS: The population studied were all violent causes of death of people
      between 10 to 24 years old, of Argentina, since 1991 to 2000. The violent causes
      of death studied were: Accident (other than traffic), traffic accidents, suicide,
      homicide, between 10-14 year old, 15-19 year old and 20-24 year old, male and
      female youngsters. STATISTICAL ANALYSIS: Mortality rates were calculated on
      yearly basis per province and per country. RESULTS: Of 100% of death causes among
      10-24 years old adolescents: 15% were accidents (non traffic), 14,6 traffic
      accidents, 10,1% homicides and 9,1% were suicides. Mortality rates were higher
      for males, in all ages and during all the period. We observed an increase in
      external causes of death during 1991 to 2000. Mortality rates of homicide and
      suicide increased for males between 1991 and 2000. DISCUSSION: Adolescents (15-19
      year old) and male gender are risk factors for external causes of death
      (accidents, aggression and suicide). The results of this study showed that
      mortality by violent causes should be a priority problem for the Public Health
      and for all the community.

PMID- 14647547
TI  - Is there a need to involve doctors in management of health care in Saudi Arabia.
AB  - Recently, the role of doctors and managers in health care management has become a
      hot topic in the newspapers and public magazine in the Kingdom of Saudi Arabia.
      The aim of this paper is to contribute constructively and scientifically to this
      topical issue by emphasizing that commonality and interaction between medicine
      and management dictate more involvement of doctors in management. Although one
      may argue that doctors are usually not well trained in resources management,
      scientific evidence supports the need for more involvement of doctors in managing
      health care system. In addition, government needs to make a strategic shift
      towards high quality primary and preventive care to enable doctors in management
      role to maintain essential services and contain cost.

PMID- 14647548
TI  - A new era for preventive genetic programs in the Arabian Peninsula.
AB  - In the Arabian Peninsula, high percentages of consanguineous marriages and the
      tribal nature of marriages have resulted in high incidence of genetically based
      disorders. The successful management of these disorders incurs a high financial
      cost, which is a great burden on the health care system. The practical solution
      to this problem is through prevention. Prevention of genetic disorders should be
      the utmost public health concern especially where these disorders are prevalent.
      Preventive genetics became possible with the advent of biochemical and molecular
      technologies. Biochemical neonatal screening based on tandem mass spectrometry
      technology and molecular technologies such as sequencing, DNA microarray and
      nucleic acid hybridization techniques are steadily being transferred to clinical
      practice. Preventive genetics could be best achieved through establishment of
      databases for common genetic disorders, premarital diagnosis, and pre
      implantation genetic diagnosis and by genetic counseling. These preventive
      measures must take into account the social and cultural aspects.

PMID- 14647549
TI  - Health hazards of welding fumes.
AB  - Even in the twenty-first century, welding is still a common and a highly skilled
      occupation. The hazardous agents associated with welding processes are acetylene,
      carbon monoxide, oxides of nitrogen, ozone, phosgene, tungsten, arsenic,
      beryllium, cadmium, chromium, cobalt, copper, iron, lead, manganese, nickel,
      silver, tin, and zinc. All welding processes involve the potential hazards for
      inhalation exposures that may lead to acute or chronic respiratory diseases.
      According to literature described earlier it has been suggested that welding
      fumes cause the lung function impairment, obstructive and restrictive lung
      disease, cough, dyspnea, rhinitis, asthma, pneumonitis, pneumoconiosis, carcinoma
      of the lungs. In addition, welding workers suffer from eye irritation,
      photokeratitis, cataract, skin irritation, erythema, pterygium, non-melanocytic
      skin cancer, malignant melanoma, reduced sperm count, motility and infertility.
      Most of the studies have been attempted previously to evaluate the effects of
      welding fumes. However, no collectively effort illuminating the general effects
      of welding fumes on different organs or systems or both in human has not been
      published. Therefore, the aim of this review is to gather the potential toxic
      effects of welding fumes documented by individual efforts and provide
      informations to community on hazards of welding.

PMID- 14647550
TI  - Source of job stress for nurses in public hospitals.
AB  - OBJECTIVE: This study aims at assessing the different sources of job stress for
      nurses in a number of public hospitals in Riyadh city, Kingdom of Saudi Arabia.
      In addition, it intends to find out the most and least perceived sources of
      stress, and the effect of demographic factors on nurses perception of these
      sources. METHODS: Four-hundred and twenty-four nurses working in a number of
      public hospitals in Riyadh city were the sample size. A questionnaire was used as
      a method of data collection. It was distributed through the first half of year
      2002. Validity and reliability were examined and the score of Cronbachs alpha was
      found at.92. Furthermore, a number of statistical techniques such as mean,
      standard deviation, and regression analysis were used to examine the research
      questions. RESULTS: Six possible sources of job stress for nurses in public
      hospitals were found. These include organizational structure and climate, job
      itself, managerial role, interpersonal relationships, career and achievement and
      homework interface. The major sources of stress were the first 3 factors, but
      they have mixed views on the last 3. Homework interface was not seen as a source
      of stress for nurses, which may refer to the fact that most of them are
      expatriate and may have little familial obligations. On the other hand, it was
      found that the effects of demographic factors on nurses perception of these
      sources are little. The exception was between age and marital status regarding
      homework interface factor. It was found that old and unmarried nurses did not see
      this factor as a stressor on the contrary to young and married ones. CONCLUSION:
      There are many sources of job stress for nurses in public hospitals. The most
      stressors found were organizational structure and climate, the nursing job
      itself, and the managerial roles. Public hospitals managers must deal with these
      and other stressors and manage them more constructively in a way that positive
      consequences will be maintained, and negative ones will be eliminated. Besides,
      there are many strategies for coping with job stress that managers should adopt.
      Finally, it must be noted that these results have to be taken with caution. More
      research in this area is needed before generalizing the study findings.

PMID- 14647551
TI  - Students perception of the various teaching methods used in the primary health
      care course in the Abha, College of Medicine.
AB  - OBJECTIVE: To describe students perception of the various teaching methods used
      in the Primary Health Care (PHC) course concerning the scientific material
      presented, information processing as well as motivation and importance attached
      by the students to each method. METHODS: A self-administered anonymous
      questionnaire was filled by the students of the sixth year (n=51) at the end of
      the course. This was structured into 3 main parts: a general part addressing the
      objectives of the course, the suitability of the course contents, the references
      and the importance of the course for the future career. The second part dealt
      with the suitability of the used teaching methods and the last part was for
      students scoring to items related to scientific material, information processing
      and motivation for each method. The study took place in the scholar year 2001
      2002. RESULTS: A high percentage of students (93.3%) agreed with the importance
      of the course, the objectives were fully fulfilled for 72.1% of students while
      two thirds of students (66.7%) felt that there is a need to add or remove topics
      from the course. The practical sessions were suitable methods for 76.7% of
      students and clinical sessions for 73.3% of students. Seminars had the lowest
      scores for understanding the scientific material presented (mean score 5.8) as
      well as the lowest score for enhancing critical thinking (mean score 4.0).
      Lectures and problem solving exercises received fairly good attendance priority
      (mean scores 8.3 and 8.7). CONCLUSION: The teaching methods for the PHC course
      need to be reviewed in the light of the present study. Students perceptions are
      to be studied regularly in order to tailor courses that meet the needs of the
      students and reach an acceptable standards.

PMID- 14647552
TI  - Deniz: the electronic database for beta-thalassemia mutations in the Arab world.
AB  - OBJECTIVE: Data on the distribution of beta-thalassemia mutations in Arab
      populations are usually destined to disparate locations and much of these become
      increasingly difficult for an average researcher to locate. That is why we aimed
      at establishing an electronic database network, called Deniz, for beta
      thalassemia allele frequency distributions in the Arab world at
      http://biobase.fatih.edu.tr. METHODS: The scheme of the database combines the
      benefits of the relational and hierarchical systems. Detailed statistics of the
      frequencies of beta-thalassemia mutations are retrieved in tabular forms.
      Multiple permanent connections allow flexible movement within the database.
      Queries are processed by the systems language and sent to the user's browser as
      hypertext markup language documents. RESULTS: The database catalogues the
      frequencies of beta-thalassemia mutations in 14 Arab countries as pooled from the
      analysis of 3,138 chromosomes by 36 laboratories. Of the 57 B-globin gene
      mutations reported in Arabs, IVS-I-110 (G-A), IVS-I-5 (G-C), IVS-I-6 (T-C), IVS
      II-1 (G-A), and IVS-I-1 (G-A) are the most encountered and they account for
      approximately two thirds of the Arab chromosomes registered in Deniz. CONCLUSION:
      In addition to its importance as a hub of updated information on the distribution
      of beta-thalassemia mutations in Arabs, information in Deniz may be used to
      predict diagnostic strategies that may be offered to natives of unstudied
      countries. Incidence data may also give important clues on the possible origins
      of beta-thalassemia in the Arab world. The integration of Deniz with other
      databases is currently in process and researchers are invited to contribute to
      the growth of the database.

PMID- 14647553
TI  - Quick gene expression profiling of promyelocytic cell line HL-60.
AB  - OBJECTIVE: A number of techniques have been developed to perform gene expression
      profiling. We report preliminary results from our exploratory study, using
      sequential analysis of gene expression (SAGE) technique, to profile the
      undifferentiated and differentiated HL-60 cells in line with our interest to
      characterize the cancer phenotype. The aim of the study is to evaluate the
      technique and to understand the molecular bases of these 2 states of cells.
      METHODS: HL-60 cells were differentiated after treatment with dimethyl sulfoxide.
      Tag libraries were prepared from the messenger RNAs of the undifferentiated and
      differentiated cells according to the SAGE protocol. The search for genes
      corresponding to the tags was carried out using SAGE software. The tags and the
      genes from the 2 libraries were compared for their levels of expression. The
      study was carried out at the King Faisal Specialist Hospital and Research Centre,
      Riyadh, Kingdom of Saudi Arabia during the year 2001. RESULTS: A comparison of
      tags from the 2 libraries revealed that 151 tags corresponding to 57 genes
      expressed differentially: 60 tags were elevated and 59 were repressed in the
      undifferentiated cells. Thirty-two tags were equally expressed in both types of
      cells. Of the corresponding genes, 25 were expressed at higher, 17 at lower,
      while 15 were expressed at comparable levels in both cell types. In the profile
      of undifferentiated cells, the genes involved in mitochondrial function and
      protein synthesis were prominent, while in the differentiated cells, the genes
      coding for proteins associated with cell membranes, signal transduction and for
      cell specific functions were prominent. The genes, expressed equally in both the
      cell types, were concerned with the maintenance of the living state. CONCLUSION:
      Sequential analysis of gene expression is a useful technique for gene expression
      profiling. As previously indicated by others, a dedicated team can generate
      useful data within reasonable time limits.

PMID- 14647554
TI  - Pitfalls of inhalation technique in chronic asthmatics. Effect of education
      program and correlation with peak expiratory flow.
AB  - OBJECTIVE: To determine the pattern of pitfalls of inhalation technique in
      chronic asthmatics; to assess whether an educational program can reduce the
      pitfalls of inhalation technique; and to evaluate whether reduction of the
      pitfalls could have a positive correlation with peak expiratory flow (PEF)
      measurements. METHODS: The pitfalls of inhalation technique in 106 chronic
      asthmatics using either metered dose inhaler (MDI) (65%) or turbuhaler (35%) were
      studied prospectively. The pitfalls of inhalation technique and PEF measurement
      were recorded before and after an educational program at first and second visit.
      It was performed in the outpatients asthma clinic of the King Abdul-Aziz
      University Hospital, Jeddah, Kingdom of Saudi Arabia, from October 2001 until
      March 2002. RESULTS: Among the MDI group; failure to breath hold for 5-10 seconds
      (52.2%) and failure to breath in slowly and deeply after inhaler activation
      (46.4%) were the most common pitfalls that have been reduced after education
      (20.3%, 21.7%). While in the turbuhaler group; failure to breath hold for 5-10
      seconds (23.1%) and failure to twist the grip forward and backward before use
      (21.1%) were the most common pitfalls that have been reduced after education (0%,
      0%). In both groups, the education program has been significantly contributed in
      reducing the mean number of pitfalls among MDI and turbuhaler users with p<0.001
      and p=0.002. Moreover, the mean PEF has been improved significantly from 312.4 +/
      109.9 l/minute to 331+/- 105.8 l/minute (p=0.003). CONCLUSION: An educational
      program used in the outpatients asthma clinic has been significantly reduced the
      pitfalls of inhalation technique. The reduction of the pitfalls correlated
      positively with an increase in the PEF measurement. Therefore, we recommend such
      an education to be used in patients using such inhalers.

PMID- 14647555
TI  - Penicillin resistance in serogroups/serotypes of Streptococcus pneumoniae causing
      invasive infections in Central Saudi Arabia.
AB  - OBJECTIVE: To determine the minimum inhibitory concentrations (MICs) of
      penicillin, ceftriaxone and vancomycin of serogroups/serotypes of Streptococcus
      pneumoniae (S. pneumoniae) from invasive diseases in all age groups from major
      hospitals in Riyadh, Kingdom of Saudi Arabia (KSA). METHODS: All isolates of S.
      pneumoniae from patients with invasive pneumococcal infections between February
      2000 and November 2001 were prospectively collected from 8 major hospitals in
      Riyadh, KSA. The isolates were confirmed as S. pneumoniae at the King Khalid
      University Hospitals, Riyadh, KSA and then serogrouped/serotyped using the
      agglutination method. The MICs for penicillin, ceftriaxone and vancomycin were
      carried out using the E-test. RESULTS: Forty-three percent of the isolates were
      resistant to penicillin mostly of the intermediate type (97%). The resistant
      strains were mainly confined to serogroups/serotypes 6, 23, 19 and 15 and the 7
      valent conjugate vaccine covers 76% of the penicillin-resistant strains. Only one
      isolate was resistant to ceftriaxone. CONCLUSION: In view of the rather
      insignificant level of highly resistant-penicillin strains and the virtual
      absence of resistance to ceftriaxone we would like to suggest using ceftriaxone
      for treating invasive pneumococcal infections outside the central nervous system.
      We recommend that the conjugate vaccine would be a useful adjunct to penicillin
      prophylaxis in patients at risk in our community.

PMID- 14647556
TI  - Primary hyperparathyroidism.
AB  - OBJECTIVE: The aim of the study is to present the clinical pattern, surgical
      indication and management of primary hyperparathyroidism in a teaching hospital
      in the Kingdom of Saudi Arabia (KSA). METHODS: The records of patients who
      underwent surgical treatment for primary hyperparathyroidism at the King Khalid
      University Hospital, Riyadh, KSA from March 1992 to October 2002 were reviewed
      for epidemiological data, biochemical, radiological investigation, operative
      procedures, histopathology result, preoperative localization studies included
      neck ultrasonogram, neck computerized tomography and thallium-technetium
      subtraction scan. All patients underwent surgery under general anesthesia and
      procedures were bilateral, unilateral neck exploration, or minimal invasive
      parathyroidectomy. RESULTS: A total of 41 patients with diagnosis of primary
      hyperparathyroidism were reviewed. There were 30 females and 11 males with a mean
      age of 42 years (range 14-78 years). The musculoskeletal symptoms were the major
      symptoms in 30 patients (73%) followed by renal stone in 6 patients (14.6%),
      peptic ulcer in 2, acute pancreatitis in one, asymptomatic patients accounted for
      5% (2 patients) and the thallium-technetium scan has the highest sensitivity rate
      (89%) among the preoperative localization studies. The histopathological results
      showed adenoma in 36 cases (87.8%), hyperplasia in 3 cases (7.3%) and no
      pathology found in 2 cases. CONCLUSION: Almost all the patients presented with
      late symptoms and complications of primary hyperparathyroidism, the number of
      asymptomatic patients, is low due to lack of routine serum calcium check up.
      Owing to the high sensitivity of thallium-technetium scan and the relatively low
      incidence of hyperplasia (7.3%), we believe that unilateral neck exploration
      guided by preoperative scan is a suitable procedure for primary
      hyperparathyroidism.

PMID- 14647557
TI  - Risk factors, knowledge and health status in diabetic patients.
AB  - OBJECTIVE: This study aimed to assess the prevalence of risk factors, knowledge
      and awareness in Pakistani patients with type 2 diabetes mellitus (DM). METHODS:
      We studied 120 DM patients at the Diabetes Center in Rawalpindi, Pakistan, from
      February 2001 to July 2001. Structured questionnaires, clinical and laboratory
      assessments were used to determine the prevalence of dyslipidemia, glycemic
      control, hypertension, self monitoring of blood glucose, treatment for
      hyperglycemia, smoking and modes of diagnosis. The patients knowledge was
      assessed as regards to the laboratory investigations and treatment of DM that
      they are receiving. Fasting blood samples were analyzed for serum total
      cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), glucose and glycosylated hemoglobin
      (HbA1c). RESULTS: It was found that 46.7% of subjects had poor glycemic control
      (HbA1c >7.5%). There was a higher prevalence of obesity (body mass index >30) in
      females (30%) as compared to males (11.4%). Approximately 56.7% of subjects had
      moderate to high-risk levels of serum total cholesterol, LDL-C 66.7%, HDL-C 46.7%
      and triglycerides 16.7%. Prevalence of hypertension was 48.3% (41.7% had systolic
      and 28.3% had diastolic hypertension). Approximately 46% of hypertensive subjects
      were unaware of their hypertension. The prevalence of hypertension was higher in
      patients who had a positive family history of DM. On regression analysis, poor
      glycemic control (raised HbA1c levels) was positively related with total
      cholesterol (coefficient correlation [r] = 0.24) (p<0.05) and LDL-C [r = 0.28]
      (p<0.05) levels and negatively related with HDL-C [r = 0.49] (p<0.0001).
      CONCLUSION: There is a high prevalence of poor glycemic control and atherogenic
      dyslipidemia in Pakistani patients with type 2 DM. Most of these diabetics have
      poor knowledge of their disease and are unaware of its complications.

PMID- 14647558
TI  - Profile of Pap smear cytology in the Western region of Saudi Arabia.
AB  - OBJECTIVE: Cervical carcinoma is an important women's health problem in the
      Western countries. There are only few published data on this disease in the
      Kingdom of Saudi Arabia (KSA). The aim of this study is to evaluate the abnormal
      cytological entities detected by cervical Pap smear in Western region of KSA and
      to discuss the importance of Pap smears screening programs. METHODS:
      Retrospective review of all the cervical smears present at the King Abdul-Aziz
      University Hospital, Jeddah, KSA from 1984 to 2000. The reports of 22089 smears
      were retrieved from the file of the pathology department. RESULTS: There were 368
      (1.66%) abnormal Pap smears out of 22089 smears. Out of these 368 abnormal Pap
      smears there were 62 (16.8%, mean age 37 year) cervical intraepithelial neoplasia
      grade 1, 45 (12.2%, mean age 38.5) cervical intraepithelial neoplasia grade 2, 27
      (7.3%, mean age 40.5) cervical intraepithelial neoplasia grade 3, 22 (6%, mean
      age 38.5) positive for malignant cells, 36 (9.8%, mean age 40.5) atypical
      endocervical cells, 88 (23.9%, mean age 39) atypical squamous cells, 9 (2.4%,
      mean age 40.5) squamous metaplasia with atypia, 26 (7.1%, mean age 45) squamous
      cell carcinoma, 6 (1.6%, mean age 36.5) reparative atypia, 2 (5.4% mean age 35)
      herpes virus changes, 19 (5.1%, mean age 37.5) human papilloma virus changes, 5
      (1.4%, mean age 55) adenocarcinoma of endometrium, and 7 (1.9%, men age 43.5)
      adenocarcinoma of endocervix. CONCLUSION: Cervical intraepithelial neoplasia and
      invasive cervical carcinoma are less common in KSA compared to the Western
      countries, however, cervical screening programs are necessary nationwide to
      estimate the actual magnitude of cervical carcinoma and its precursor lesions.

PMID- 14647559
TI  - The outcome of pregnancy in elderly primigravidas.
AB  - OBJECTIVE: To investigate the effect of advancing age of 35 years and more
      (elderly primigravida) on the outcome of pregnancy in nulliparous women and to
      compare the type of complications observed in this group of women to those in the
      age of 20-34 years. METHODS: This was a retrospective analysis of 2517
      primigravidas delivered at King Fahd Hospital of the University, Al-Khobar,
      Kingdom of Saudi Arabia between 1996-2000. All were consecutive patients. The
      data were collected from the records of the labor room and the medical records
      were screened for maternal age, antenatal complications, gestational age, birth
      weight of the neonate, sex of the neonate and the Apgar score. RESULTS: Three
      hundred and sixty-two nulliparous were below the age of 19 years; hence, excluded
      from the study group. Between age of 20-34 years (Group A) there were 1950
      patients with the mean age of 24.79 years (range 20-34) and in women over the age
      of 35 years (Group B) there were 205 patients with the mean age of 38.72 years
      (range 35-48 years). Group B had significantly less number of normal deliveries
      59.9 compared to group A 81% with p value of <0.001. Diabetes mellitus was common
      in group B as compared to group A and was statistically significant at p value
      <0.001. The gestational age in group B was 36.06 weeks and in group A it was
      38.84 weeks (p value was markedly significant at <0.001). Women in group B had
      more deliveries by cesarean section (CS) 23.8% as in group A 12.6%, a significant
      p value <0.001. The Apgar score at 1 and 5 minutes was significant at p value
      <0.001 and <0.004. The birth-weight in group B was less compared to group A, p
      value of <0.002. CONCLUSION: Childbearing in elderly primigravidas does have
      higher rates of complications due to diseases such as diabetes mellitus and
      preeclamptic toxemia. They are liable to have more deliveries by CS than by other
      methods, in spite of lower gestational age and birth weight. The overall outcome
      however does not appear grim, as was once believed. This study suggests that
      women in the age group of >35 years should be informed of their pregnancy
      expectations and outcomes.

PMID- 14647560
TI  - Management of acute myocardial infarction. Do we follow guidelines applied in
      practice?
AB  - OBJECTIVE: Acute myocardial infarction (MI) is a major health problem with a
      substantial fatality and morbidity. The management of patients with acute MI has
      been addressed in major trials to improve the survival and enhance the quality of
      life of the patients. Numerous guidelines have been established for the
      management of such patients. The objective of this study is to determine whether
      the current practice in managing patients admitted with acute MI in a major
      community hospital in Riyadh is evidence based compliant. METHODS: The data were
      collected from patients admitted to the Coronary Care Unit (CCU), Riyadh Medical
      Complex (RMC), Riyadh, Kingdom of Saudi Arabia, a 1500 bed community hospital,
      with a diagnosis of acute MI over one-year period (April 1999 to April 2000). The
      administration of different therapeutic modalities upon admission as well as
      discharge medications was obtained. Patients outcome (all cause mortality) post
      treatment were collected. The data was analyzed and compared with the current
      guidelines. RESULTS: A total of 335 patients, 315 males (94%), were admitted to
      the CCU of RMC with a diagnosis of acute MI. Two hundred and seventy-one patients
      (80.9%) received thrombolytic therapy. Discharge medications were beta-blocker in
      255 (76.1%), angiotensin converting enzyme inhibitors in 206 (61.5%), nitrates in
      281 (83.9%), hypolipidemic agents in 15 patients (4.5%), and aspirin in all
      patients. The outcome of these patients obtained either alive or dead was 313
      (93.4%) and 22 (6.6%) (p<0.00001). CONCLUSION: The patients with acute MI
      received management compliant with evidence-based practice. However, more
      awareness to the use of angiotensin converting enzyme inhibitors as well as
      hypolipidemic agents is needed to provide maximum benefit to these patients.
      Moreover, national guidelines for the management of acute MI are needed for
      improvement of quality of care.

PMID- 14647561
TI  - Incidence of intraoperative hypothermia. Adopting protocol for its prevention.
AB  - OBJECTIVE: To determine the incidence of hypothermia during surgical procedures
      when adequate methods of preserving normothermia are applied. METHODS: A
      prospective study in which patients ASA I-IV presented for surgery at the Armed
      Forces Hospital, Wadi Al-Dawasir, Kingdom of Saudi Arabia during the period from
      July 2000 until February 2003, in whom body core temperature was between 35-37
      degree, were included. Ambient temperature of the operating room was
      thermostatically adjusted to record 26 degree and 24 degree if patients were less
      than 10 year-old or above. Depending on type of surgery; the patients were
      provided with space blankets and were lying on warm mattresses. Fluid or blood
      warmers and forced-air surface warming were used when needed. RESULTS: There were
      3886 surgical patients operated upon during the period of the study. Their
      average age was 34.5 years (range 15 days to 104 years). Sixty patients (1.54%)
      developed intraoperative hypothermia (core temperature <35 C) and were admitted
      to the intensive care unit for monitoring and gradual rewarming. There was no
      mortality amongst them. Out of those 60 patients, 17 (28.3%) expressed
      dissatisfaction on this part of the service, but the overall patient's
      satisfaction scored 99.6%. CONCLUSION: Aggressive measures must be adopted to
      preserve normothermia as prevention of intraoperative hypothermia improves
      patient's outcome. All patients should have their core body temperature monitored
      during surgery. However, application of available methods of keeping normothermia
      reduces the incidence of intraoperative hypothermia but does not abolish it
      completely. Hypothermic patients should be closely monitored during gradual
      rewarming, preferably in the intensive care setting. A protocol for prevention of
      intraoperative hypothermia must be adopted by all operating theaters.

PMID- 14647562
TI  - Prevalence of medically compromised patients referred for periodontal treatment
      to a teaching hospital in Central Saudi Arabia.
AB  - OBJECTIVE: Many patients seeking dental care have a significant medical condition
      that may alter both the course of their oral disease and the treatment provided.
      The aim of this study was to assess the systemic diseases profile of patients
      with periodontal diseases for specialized periodontal treatment. METHODS: Seven
      hundred and forty-three patient's medical records were screened from the
      Periodontal Clinics and referred to the College of Dentistry, King Saud
      University, a teaching hospital in Riyadh, Kingdom of Saudi Arabia for a special
      care during the period from January 2002 to June 2002. RESULTS: One hundred and
      sixty-seven were males while 576 were females. The age ranged was from 18-64
      years. Approximately 90% of the patients were systemically healthy. The remaining
      10% of the patients were with different systemic diseases or sequelae. Diabetes
      mellitus, hypertension, asthma and rheumatic fever were most commonly present.
      Thirty-one (4.2%) of the medically compromised were diabetic. Hypertension was
      reported in 9 (1.2%) patients. Rheumatic fever and asthma were equally present in
      7 (0.9%) patients. Periodontal diseases were equally prevalent in both male and
      female patients. Approximately 50% of the patients had moderate periodontitis
      while severe periodontitis was common among 9% of the male and female patients.
      CONCLUSION: Diabetes and heart related conditions were most common among the
      specialist patients referred for periodontal treatment. The advanced
      periodontitis was prevalent among 9% of the patients. It is recommended that
      physicians are become more familiar with the systemic associations to periodontal
      diseases. The dental practitioners should be well versed in the interplay between
      oral and systemic disease. More extensive knowledge of oral and physical medicine
      will be needed in order to provide quality care and appropriate treatment of
      patients with periodontal diseases suffering with systemic conditions.

PMID- 14647563
TI  - Metallothionein expression in human prostate gland.
AB  - OBJECTIVE: This study is conducted to detect metallothionein (MT) distribution in
      the epithelial cells of prostate gland from patients with benign prostatic
      hypertrophy and adenocarcinoma. METHODS: Prostatic tissues from patients with
      benign prostatic hypertrophy and adenocarcinoma were processed for
      immunocytochemistry using indirect peroxidase antiperoxidase procedure and
      primary antibody against MT. The samples were collected over a period of 2-3
      years and were processed at Jordan University of Science and Technology, Irbid,
      Jordan in the year 2002. RESULTS: All prostatic tissues showed a positive
      reaction for MT. In benign prostatic hypertrophy, MT was mainly localized in the
      nuclei of epithelial cells while in the adenocarcinoma; MT was mainly localized
      in the cytoplasm of the epithelial cells. CONCLUSION: Metallothionein expression
      may be affected by the pathological status of the prostate. In addition, these
      findings could be used in diagnosing and evaluating the prognosis of different
      pathological conditions of the prostate.

PMID- 14647564
TI  - Successful pregnancy in a patient with Takayasus arteritis.
AB  - This report describes a case of Takayasus arteritis in a 19-year-old Palestinian
      female. She conceived after diagnosis. Her pregnancy was complicated by
      uncontrolled hypertension, which was not associated with other markers of disease
      activity. Despite aggressive medical treatment, cesarean section had to be
      carried out at 34 weeks of pregnancy because of uncontrolled hypertension. A live
      fetus was borne, and her blood pressure was subsequently controlled with a single
      antihypertensive agent.

PMID- 14647565
TI  - Pelvic hematoma resulting in obstructive uropathy.
AB  - The use of anticoagulants, for whatever indication, may carry a high risk of
      hematoma formation following surgery. Obstructive uropathy is a very rare but
      possible example of complication secondary to an extensive pelvic hematoma. We
      describe a case of a patient with rheumatic heart disease and aortic valve
      replacement, who developed a massive postoperative pelvic hematoma following
      bilateral tubal ligation, resulting in bilateral ureteric obstructions. This was
      treated with bilateral ureteric stent through cystoscopy.

PMID- 14647566
TI  - The pathological expressions of Brunners gland hyperplasia into adenoma and
      hamartoma.
AB  - The terms Brunners gland adenoma and hamartoma are 2 pathological expressions of
      hyperplasia of these glands. We report 3 patients and review the recent
      literature to support our hypothesis of common pathology. Awareness of the
      existence and character of Brunners gland lesions will increase the possibility
      of their accurate diagnosis.

PMID- 14647567
TI  - Bilateral simultaneous hip fractures secondary to an epileptic seizure.
AB  - A 30-year-old man sustained bilateral simultaneous displaced subcapital fractures
      of neck of femur during an epileptic tonic-clonic seizure. After admission to the
      hospital approximately 18 hours later, internal fixation of the fractures with
      dynamic hip screw was undertaken. Post operatively, he was managed by early
      motion and weight bearing on the second day. Despite the severity of the
      fractures and delayed surgery, satisfactory union of the fractures was noted at 6
      months when bone densitometry was normal. At 3 years follow up, there was no sign
      of avascular necrosis of the femoral heads.

PMID- 14647568
TI  - Erythrokeratoderma variabilis.
AB  - Erythrokeratoderma variabilis is a rare autosomal dominant genodermatosis of
      variable expressivity. In this report, we describe the clinical features and
      microscopic findings in one of our patients born to unaffected parents. We also
      briefly review the literature on this disorder.

PMID- 14647569
TI  - Preference of medical students in clinical year.

PMID- 14647570
TI  - Unmet need for family planning.

PMID- 14647571
TI  - Does tuberculin skin test predict tuberculosis in patients with end-stage liver
      disease?

PMID- 14647572
TI  - The prevalence of antibodies against rubella in pregnant women in Kerman, Iran.

PMID- 14647573
TI  - Tepid blood versus cold crystalloid cardioplegia in cardiac protection.

PMID- 14647575
TI  - [Intrauterine growth curves: the use of local growth charts]

PMID- 14647574
TI  - Prescribing for asthmatic children in primary care. Are we following the
      guidelines?

PMID- 14647576
TI  - [Neonatal asphyxia and thyroid function]

PMID- 14647578
TI  - [Malnutrition and neuropsychomotor development]

PMID- 14647577
TI  - [Post-extubation laryngitis:. easy breathing?]

PMID- 14647579
TI  - [Monosymptomatic nocturnal enuresis]
AB  - OBJECTIVES: Monosymptomatic nocturnal enuresis (MNE) plays a very important role
      in the practice of pediatrics due to its high prevalence, its psychosocial
      impact, and its controversial etiology and treatment. Our objective was to show
      that MNE can be a well-defined clinical entity (monosymptomatic), but it can also
      be a symptom of urinary disorder, thus requiring a completely different
      therapeutic approach. METHODS: The literature presents numerous publications
      related to the matter of MNE, thus we tried to select, for this review, the
      classical and the most recent publications from internationally recognized
      authors; in addition, we also have a 13-year work experience at the Unit for
      Urinary Disorders of the Pediatric Nephrology Center of the state of Parana
      (Unidade de Disturbios Miccionais - Centro de Nefrologia Pediatrica do Parana).
      RESULTS: The lack of a well-defined, international consensus on the concept,
      terminology, and classification of MNE is an obstacle for the assessment of the
      numerous studies found in the literature. The individualization of the MNE
      clinical entity is the fundamental starting point for providing appropriate
      guidance for patients. Enuresis can be found in most societies and, thus, it
      gives way to several interpretations and forms of treatment. There is a
      consensus, however, on the damage to the self-esteem of enuretic children, and
      consequently, on the advantage of proper treatment. CONCLUSIONS: In most cases,
      MNE is kept as a family secret while children remain without proper guidance and
      treatment and suffering with the lack of understanding and damage to their self
      esteem. Doctors should survey patients extensively for MNE during pediatric
      appointments. It is possible to discard other diagnoses with a detailed survey of
      habits, quality of the urination, and history of urinary infection and a
      meticulous physical examination. MNE should be faced as a medical problem worthy
      of the attention of professionals and patients families.

PMID- 14647580
TI  - [Intrauterine growth curves in a high-income population]
AB  - OBJECTIVE: Growth curves can be used to assess intrauterine growth, to predict
      diseases in newborns, and to characterize different populations. The objective of
      this study was to obtain intrauterine growth curves of newborns from the
      maternity ward of the Hospital Albert Einstein (MAE) and compare them with
      intrauterine growth curves of a population from California, USA. METHODS: We
      plotted the growth curves according to weight at birth and gestational age, which
      was obtained according to information from the mother, after the 32nd week of
      gestation, between February 1995 and February 1999. We calculated the birth
      weights for the 10th, 50th, and 90th percentiles by each gestational age and
      compared them with those presented by California growth curves. RESULTS: The
      growth curves for the 10th and the 50th percentiles did not differ from the
      California growth curves. For the 90th percentile, however, the MAE growth curves
      were lower than those of California. The MAE population presented fewer small-for
      gestational age (SGA) and big-for-gestational age (BGA) newborns when assessed
      according to the California curves. The categories of SGA, normal, and BGA for
      both male and female newborns indicated a statistically significant relation with
      the weight gain of mothers. CONCLUSIONS: The two populations assessed in this
      study were different according to intrauterine growth curves. Further studies
      should be carried out in order to identify specific factors that may be acting on
      the MAE population.

PMID- 14647581
TI  - [Effect of perinatal asphyxia on thyroid hormones]
AB  - OBJECTIVE: To verify the effect of perinatal asphyxia on thyroid hormone levels
      in term newborn infants. METHODS: We carried out a case-control study with 17
      term and asphyxiated (A) and 17 term and control (N) newborn infants at the
      Hospital de Clinicas de Porto Alegre. Patients were paired according to color of
      skin, sex, type of delivery, gestational age, and weight at birth. We collected
      umbilical cord plasma T4, T3, free T4, reverse T3, and TSH after 18 to 24 hours
      of life and from asphyxiated and control newborn infants. RESULTS: There were no
      differences in thyroid hormones of cord blood, with the exception of reverse T3,
      which was higher in A than in controls [median (25th-75th percentile): A= 2(1.4
      2); N= 1.41 (1.13-1.92); P=0.037)]. Thyroid hormone levels were lower in A than
      in controls on samples collected within 18-24 hours after birth, except for
      reverse T3, which was similar in both groups [average -/+ SD: T4 A= 9.79 -/+
      2.59; N=14.68 -/+ 3.05; P<0.001; median T3 A= 40.83 (37.4-80.4); N= 164 (56.96
      222.5); P=0.003; average -/+ SD: free T4 A=1.85 -/+ 0.92; N= 2.8 -/+ 0.74;
      P=0.004; median: reverse T3 A=1.54 (1.16-1.91); N=1.31(0.87-2); P=0.507; TSH
      A=9.1 (6.34-12.95); N=14.5(12.9-17.85); P=0.008]. CONCLUSIONS: Our data suggest
      that lower T4, free T4, and T3 levels are secondary to lower TSH levels in
      asphyxiated newborns; also, peripheral metabolism of T4 in asphyxiated infants
      can be altered due to low T3 and normal reverse T3 levels.

PMID- 14647582
TI  - [Efficacy and safety of nebulized L-epinephrine associated with dexamethasone in
      postintubation laringitis]
AB  - OBJECTIVE: To assess the efficacy and safety of the use of nebulized L
      epinephrine associated with dexamethasone in postintubation laryngitis. METHODS:
      We carried out a prospective, randomized, double-blind, placebo controlled study
      with two cohorts of patients with postintubation laryngitis graded 3 to 6 by
      Downes-Raphaelly score during two years. Our population was divided into two
      groups: A and B; both groups received intravenous dexamethasone and two doses of
      nebulized saline; however, only group B received L-epinephrine. The efficacy was
      assessed by Downes-Raphaelly score. The side effects of L-epinephrine were
      evaluated according to the occurrence of cardiac arrhythmia, increased blood
      pressure, and average heart rate of group B in comparison to group A. RESULTS:
      Twenty-two patients were included in group A (average score = 4.8) and 19 in
      group B (average score = 5.2). During treatment, 3 patients in group A presented
      a score of 8 and were reintubated. This group also showed higher mean clinical
      scores than group B during the first two hours of the protocol; these results
      were not statistically significant. No side effects were observed due to
      epinephrine. The gas blood measurements were adequate in both groups, but better
      in the control group. CONCLUSIONS: We did not observe increased efficacy for the
      treatment of postintubation laryngitis when nebulized L-epinephrine was used
      simultaneously with intravenous dexamethasone. Some indicators, however, did
      present a favorable trend when combined therapy was used and should be submitted
      to further evaluation.

PMID- 14647583
TI  - [Evaluation of neuropsychomotor development in first grade children and its
      relation with nutrition]
AB  - OBJECTIVE: To investigate the neurological performance of elementary school
      students from the city of Porto Alegre, state of Rio Grande do Sul, Brazil, in
      order to assess the association of neurological development and nutritional
      status. METHODS: We carried out an observational, analytical, and crosssectional
      study on a random and proportional population sample selected out of all first
      grade students (n=35,521) in the city of Porto Alegre for a total of 484
      children, out of which 64.7% were enrolled in state public schools, 11.9% in city
      public schools, and 23.4% in private schools. Our sample size allowed for a
      precision of -/+ 3% (95% confidence interval) for an estimated prevalence of 10%
      of cortical dysfunction. Children were submitted to individual examinations at
      the school. We collected data regarding sex, age, color of skin, nutritional
      status, and school of origin. An informed consent was obtained from the State and
      City Departments of Education and from the principals of the private schools.
      Statistical analysis was carried out using the chi-square test and ANOVA.
      RESULTS: From 11.4% to 38.2% of children presented ENE results lower than
      expected according to their age. The most affected factors were sensory activity
      and gnosia (38.2%), and the least affected factor was motor persistence (11.4%).
      There were no statistically significant differences between boys and girls. We
      observed an association of children with low height-for-age and weight-for-age
      and cortical dysfunction. CONCLUSIONS: Chronic malnutrition is a risk factor for
      brain function performance.

PMID- 14647584
TI  - [Prevalence of asthma in schoolchildren]
AB  - OBJECTIVE: To assess the prevalence of asthma symptoms and of asthma in children
      due to the high frequency of pediatrics patients with symptoms suggestive of the
      disease and to the lack of data regarding prevalence of asthma in this
      population. METHODS: We carried out a cross-sectional study with 2,735 school-age
      children aged 6-7 years and 3,509 adolescents aged 13-14 years selected by random
      sampling. Data were collected between 1998 and 1999 using a translated version of
      the questionnaire of the International Study of Asthma and Allergies in Children,
      which has been previously tested and approved. Guardians were responsible for
      answering the questionnaire of younger children, whereas adolescents answered
      their own, in classroom. The data were computed and analyzed using EPI-info
      software. RESULTS: The response rates for questionnaires were 73.2% (6-7-years
      old) and 94% (13-14 years old). The prevalence of symptoms in children and
      adolescents were, respectively: wheezing ever 46.7% and 44.3% (P<0.05); wheezing
      in the last 12 months 22.7% and 21.2%; speech limited due to wheezing 4.7% and
      4.0%; wheezing following exercise 6.3% and 18.2% (P<0.05); nighttime cough in the
      last 12 months 38.5% and 45.8% (P<0.05); asthma (bronchitis) ever 28.2% and 26.4%
      (P=0.11). CONCLUSIONS: The prevalence of asthma symptoms and of asthma of the two
      groups are among the highest results ever reported in Brazil; these results were
      compatible with those of high prevalence results reported worldwide using ISAAC
      questionnaires. The high prevalence of symptoms suggests a high prevalence of the
      disease, which makes asthma an important problem for public health in the region.

PMID- 14647585
TI  - [Diagnosis of meningitis with reagent strips]
AB  - OBJECTIVE: To determine the usefulness of reagent strips in the evaluation of
      pleocytosis, cerebrospinal fluid glucose and protein levels for early and rapid
      diagnosis of meningitis in children. METHODS: We included cerebrospinal fluid
      samples of 164 children admitted to the outpatient clinic of Communicable
      Diseases of the General Pediatric Center (Fundacao Hospitalar do Estado de Minas
      Gerais, CGP-FHEMIG) during the daytime hours from May of 1997 to May 1999, and
      who presented with clinical suspicion of meningitis. Patients ranged in age from
      one month to 12 years (median 12 months). Results from the cytological and
      biochemical assay (cellularity, cerebrospinal fluid glucose and protein levels)
      were obtained from 154 patients. These results were subsequently compared with
      the reaction of cerebrospinal fluid in reagent strips. RESULTS: The cytological
      and biochemical assay identified 43 cases of probable bacterial meningitis, 19 of
      probable viral meningitis, and 83 with no alterations. According to the reagent
      strips, there were 41 cases of probable bacterial meningitis, 2 of probable viral
      meningitis, and 71 with no alterations. By comparing the results of reagent
      strips and those of the cytological and biochemical assay, we obtained values for
      sensitivity, specificity, positive and negative predictive values, and accuracy
      (respectively 90.7; 98.1; 95.1; 96.4; and 96.1). Statistical analysis using
      McNemer test did not indicate significant differences between the two methods in
      the diagnosis of bacterial meningitis (P=0.68). Kappa statistics indicated a high
      level of agreement between the tests (P<0.0001). CONCLUSIONS: Our results suggest
      that reagent strips may be a useful additional resource in the diagnosis of
      bacterial meningitis, especially when it is difficult to collect a sufficient
      amount of cerebrospinal fluid or to indicate the initial treatment.

PMID- 14647586
TI  - [Serum immunoglobulins in children perinatally exposed to human immunodeficiency
      virus]
AB  - OBJECTIVE: Hypergammaglobulinemia is an early manifestation of perinatal HIV
      infection. Our objective was to analyze the differences in serum immunoglobulin
      levels between infected and seroreverter children and their association with
      clinical outcome. METHODS: We carried out a historical prospective study with 107
      infected and 90 seroreverter children. We compared the IgA, IgG, and IgM levels
      between infected and seroreverters in the first 18 months of life; IgA, IgG, and
      IgM as surrogate markers of infection; and IgA, IgG, and IgM levels in the first
      5 years in infected children, according to clinical outcome. The Mann-Whitney
      test was used for comparison between groups. Surrogate markers were assessed
      according to sensitivity, specificity, positive and negative predictive values,
      and J index. RESULTS: Infected children, when compared to seroreverters, showed
      significantly higher levels of: IgM from the 1st to the 5th trimester; IgA and
      IgG from the 2nd to the 6th trimester (P </= 0.05). Levels of IgA >/= 90 mg/dl in
      the 2nd trimester and IgG >/= 1,700 mg/ dl or 1,200 mg/dl in the 2nd and 3rd
      trimesters were associated with HIV infection with J indexes of 0.97, 0.92, and
      0.93, respectively. Infected children in the B and C categories, compared to
      those in the N and A, showed higher levels of IgM from the 2nd to the 4th year,
      and IgA from the 3rd to the 5th year (P </= 0.05). CONCLUSIONS: The temporal
      progression of IgA, IgG, and IgM levels showed an early and intense stimulation
      to the synthesis of immunoglobulin in infected children. Clinical and
      epidemiological indicators showed that such levels may be surrogate markers of
      infection. Higher IgM and IgA levels from the 2nd to the 5th year in more
      severely infected children suggest a dysfunction in immune regulation secondary
      to persistent antigenic stimulation.

PMID- 14647587
TI  - [Is it possible to predict the number of nebulizations and the use of intravenous
      corticosteroid in children with asthma attacks in the emergency room?]
AB  - OBJECTIVE: To identify the number of nebulizations needed and the demand for
      intravenous corticosteroids in children with asthmatic attack, considering
      clinical and functional characteristics presented at the moment children were
      admitted to the emergency room. METHODS: We prospectively evaluated 130 children
      with asthmatic attack and from 1 to 13 years of age. At the moment children were
      admitted, they were evaluated according to clinical score, arterial oxygen
      saturation (pulse oximetry), and peak expiratory flow. Next, children received a
      standard treatment and were observed for the number of consecutive nebulizations
      required and the use of corticosteroid. Using regression analysis, we assessed
      the parameters evaluated for a correlation with the number of nebulizations and
      the use of intravenous corticosteroid. RESULTS: Eighty-eight children (67.7%)
      received from 1 to 3 nebulizations and 42 children (32.3%), 6 nebulizations.
      Sixty-eight children (52.3%) received corticosteroid. The initial values for
      clinical scores, arterial oxygen saturation, and peak expiratory flow showed a
      significant correlation with the number of nebulizations required and the need
      for corticosteroids. CONCLUSIONS: According to our results, it is possible to
      predict and anticipate, at the time chidren are admitted with asthmatic attack,
      the need for corticosteroid and more nebulizations, which can change the
      prognosis and the time of evolution of the attack.

PMID- 14647588
TI  - [Nasopharyngeal colonization and antimicrobial resistance of Streptococcus
      pneumoniae isolated from children with acute rhinopharyngitis]
AB  - OBJECTIVE: To determine the prevalence and risk factors for nasopharyngeal
      colonization by, and to evaluate antimicrobial susceptibility of Streptococcus
      pneumoniae strains in children with acute rhinopharyngitis. METHODS: We collected
      nasopharyngeal swab specimens from 400 children aged 3 months to 5 years and with
      clinical status of acute rhinopharyngitis from June 16, 1997 to May 20, 1998 at
      the outpatient clinics of two hospitals in the city of Sao Paulo. Nasopharyngeal
      specimens were collected pernasally using a calcium alginate swab and plated
      immediately after collection onto trypticose soy agar with 5% sheep blood and
      garamicin 5 mcg/ml. Penicillin susceptibility was determined by oxacillin 1 mcg
      disk screening test and the minimal inhibitory concentration by the E-test.
      RESULTS: Pneumococci were recovered from 139 children, indicating a colonization
      prevalence of 35%. The risk factors analyzed indicated that the colonization was
      more prevalent in children attending day-care centers, children with siblings
      younger than 5 years, and children with recent use of antimicrobial agents. The
      prevalence of penicillin non-susceptible strains was of 16 % (20 strains). All
      strains were intermediately resistant (0.1mcg/ ml </= MIC </= 1.0 mcg/ ml). Out
      of the penicillin intermediately resistant strains, 7 (37%) showed intermediate
      resistance to cotrimoxazol and 2 (11%) full resistance to trimethoprim
      sulfamethoxazole. No strains were resistant to ceftriaxone, amoxicillin,
      clarithromicin, or chloramphenicol. CONCLUSIONS: Our findings indicate that the
      prevalence of nasopharyngeal colonization by Streptococcus pneumoniae in children
      with upper respiratory infections was of 34.8%. Children attending day-care
      centers and children with younger siblings showed higher levels of colonization
      The results of prevalence of bacterial resistance were similar to those of
      studies regarding invasive infections, thus indicating that nasopharyngeal
      isolates of Streptococcus pneumoniae can be used in the surveillance of
      antimicrobial resistance in a defined geographical area.

PMID- 14647589
TI  - [Mother-infant indicators in adolescence and youth: socio-demographic, prenatal,
      delivery and newborns]
AB  - OBJECTIVE: To identify characteristics and associations between maternal age and
      gestation, delivery, and livebirths of adolescent and young adult mothers in the
      city of Feira de Santana, state of Bahia, Brazil. METHODS: We carried out a cross
      sectional, epidemiological study with a population of livebirths and adolescent
      mothers (aged 10-16 and 17-19 years) and young adult mothers (aged 20-24 years).
      The information were obtained from the Livebirths Information System (SINASC
      1998) for a total of 5,279 livebirths. Study variables were classified into socio
      demographic factors (age, schooling of the mother, sex of the newborn) and
      related to term, delivery, gestational age, birth weight, and Apgar score. Data
      were processed using prevalence ratio and multivariate analysis. Logistic
      regression was used to control confounding factors (prenatal and gestational age)
      and to establish an association between maternal age and birth weight. RESULTS:
      In 1998, 21.6% of all livebirths in the city of Feira de Santana were from
      adolescent mothers; out of these mothers, 51.2% had not finished junior high or
      elementary school. Prevalence ratio and adjusted odds ratio for the 10-16 years
      of age group indicated increased prevalence of illiteracy, no prenatal
      examination, and low birth weight and a low prevalence of adequate weight of the
      newborn in comparison to other age groups studied. Logistic regression showed a
      positive association between maternal age and low birth weight. We also observed
      that the SINASC database lacked information in many different fields.
      CONCLUSIONS: Our results indicated, for adolescent mothers, a high prevalence of
      livebirths and low schooling. Also, especially for the 10-16 years of age group,
      we observed increased risks for illiteracy, no prenatal examinations, low birth
      weight, and inadequate weight of the newborn in comparison to other age groups.

PMID- 14647590
TI  - [Extracorporeal membrane oxygenation (ECMO) in a neonate with respiratory
      distress due to meconium aspiration syndrome: Effect of the administration of
      exogenous surfactant]
AB  - OBJECTIVES: To present the clinical outcome of a newborn with severe respiratory
      distress secondary to meconium aspiration syndrome and treated by extracorporeal
      membrane oxygenation (ECMO); and to present the effect of the use of exogenous
      surfactant in this case and the cost of the procedure. METHODS: Case report of a
      newborn with meconium aspiration syndrome and treated at the neonatal ICU of the
      Instituto da Crianca Prof. Pedro de Alcantara, Hospital das Clinicas of the
      Universidade de Sao Paulo. RRESULTS: ECMO was carried out for 5 days with no
      clinical or mechanical complications. On the 4th day of ECMO, we administered
      porcine exogenous surfactant; a significant improvement in lung compliance was
      observed and the newborn was decannulated shortly after that. Treatment costs
      were compatible with the situation of healthcare in Brazil for treatment of
      critically ill newborn patients. CONCLUSIONS: ECMO is indicated in cases of
      neonatal respiratory distress not responding to other treatments. The technique
      should be made available in neonatal Intensive Care Units (ICUs) of tertiary
      hospitals according to well-established protocols. The use of exogenous
      surfactant apparently allowed for earlier decannulation of the patient and should
      be considered in similar cases. The treatment costs do justify the organizing of
      ECMO teams in this type of ICUs.

PMID- 14647591
TI  - [On the use of recombinant human erythropoietin in preterm neonates]

PMID- 14647592
TI  - [Home ventilation of pediatric patients]

PMID- 14647593
TI  - [Gastroesophageal reflux and respiratory diseases in children]

PMID- 14647594
TI  - [Standardizing the calibration of phototherapy devices - a proposal]
AB  - OBJECTIVE: To propose a method to evaluate and maintain the efficiency of
      equipment commonly used in Brazil in order to obtain uniform results in
      phototherapy treatments in different services. MATERIAL AND METHODS: The
      radiometer/photometer used to measure spectral irradiance is locally manufactured
      and fulfills basic requirements. Measure standardization seeks to be applicable
      and reproducible to phototherapy devices employed in Brazil. The material
      necessary for measurements can be easily assembled by the neonatology staff,
      except for the radiometer. We searched Medline for papers relevant to this review
      published throughout the last 10 years. RESULTS: Irradiance in phototherapy
      issues should be referred to as "medium spectral irradiance". We describe how to
      obtain medium spectral irradiance using fluorescent and halogen phototherapies.
      COMMENTS: The components of a radiometer/photometer are described. This knowledge
      is fundamental to understanding sensibility variations and to justifying
      differences in irradiance when ranges of radiometer recording are a little
      different. The standardization of this device will certainly simplify the
      comparison between results in different services. We also analyzed
      characteristics of different equipment used in phototherapy that might interfere
      with their irradiance.

PMID- 14647595
TI  - [The effect of recombinant human erythropoietin on the treatment of anemia of
      prematurity]
AB  - OBJECTIVE: To assess the efficacy of erythropoietin in the prevention and
      treatment of anemia of prematurity, correlating the use of this drug with weight
      gain, length, and head circumference and comparing two administration schemes of
      he same weekly dose: daily use and twice a week. METHODS: The study comprised 42
      premature newborns with gestational age up to 33 weeks, birthweight up to 1550 g,
      and postnatal age between 10 and 35 days. The newborns were randomized into three
      groups: patients in group 1 received seven daily doses of 100 U/kg erythropoietin
      per week; patients in group 2 received two 350 U/kg erythropoietin doses per
      week; and patients in group 3 did not receive the drug. Hematologic measurements,
      blood transfusion requirements, and growth rates were followed during therapy.
      RESULTS: Cases and controls did not differ with respect to weight, length, head
      circumference, and total time of hospital stay. At the end of the study, no
      significant difference was observed in the platelet count measurement means,
      white blood cell count, and ferritin levels in the three groups. However, the
      final hematocrit and hemoglobin values of patients who did not receive
      erythropoietin were significantly lower than those of patients who received the
      drug. The absolute reticulocyte count mean was significantly higher in patients
      who received erythropoietin after two weeks of treatment when compared with those
      patients who did not receive the drug. Patients in group 1 e 2 received fewer
      excessive transfusions (2 or more) than patients in group 3. The administration
      of 700 U/kg/week erythropoietin significantly reduced the number of excessive
      blood transfusions. There is no significant difference in blood transfusion
      volume between patients who received erythropoietin on a daily basis and those
      who received the drug twice weekly. CONCLUSIONS: the use of erythropoietin did
      not influence weight gain and growth. The administration of 700 U/kg/week
      erythropoietin in premature infants with gestational age up to 33 weeks and
      birthweight up to 1550 g stimulates erythropoiesis and significantly reduces
      excessive blood transfusion requirements. Erythropoietin showed to be a safe and
      well tolerated medication, with no short-term side effects in the study
      population.

PMID- 14647596
TI  - [Home ventilation of pediatric patients - description of a program]
AB  - OBJECTIVE: To describe a German program for home ventilatory support, and to
      analyze the possibility of applying it in Brazil. MATERIALS AND METHODS: We
      assessed Dr. von Haunersches Kinderklinikacute;s Pediatric Intensive Care Unity -
      Ludwig-Maximilians - Universitat - Munchen (Munich, Germany) home ventilatory
      support program between April 1997 and June 1998. RESULTS: Patients aged between
      1 and 21 years - 11 boys and 15 girls - participated in the study. Fifteen out of
      26 children presented neuromuscular pathologies, 8 of them had ventilatory
      problems of central causes, and 3 children presented obstructive pulmonary
      diseases. Twelve (46.2%) were receiving noninvasive ventilatory assistance, and
      19 (73.1%) only needed intermittent ventilatory support. CONCLUSION: The program
      relies on a permanent multidisciplinary staff to treat intercurrent diseases.
      Patients, at predetermined periods, are re-evaluated as to the evolution of
      respiratory insufficiency. The adequate system organization provides patients and
      their families with security, and accounts for the success of the home
      ventilatory support program. A great deal of organizational efforts should be
      consolidated before implementing similar programs in Brazil.

PMID- 14647597
TI  - [Association between gastroesophageal reflux and dips in the oxygen
      transcutaneous saturation of the hemoglobin in infants with chronic obstructive
      ventilatory disease]
AB  - OBJECTIVE: To verify the association between oxygen desaturation episodes and the
      dips in pH in infants with chronic obstructive respiratory symptoms. METHOD:
      Cross-sectional study with children 24 months old or younger hospitalized for
      investigation of chronic obstructive respiratory symptoms from 1997 to 1999. The
      patients underwent esophageal pH monitoring associated with transcutaneous oxygen
      saturation during the night. The patients were included in the study according to
      their need to be hospitalized and availability of equipment. The indices used to
      measure this association were reflux index, total number of refluxes, number of
      refluxes longer than 5 minutes, Euler index, ZMD index, 24-hour mean pH, and mean
      pH of desaturation. RESULTS: We studied 44 children. The mean age was 7.5 months,
      and 20% had desaturation below 93% during pH monitoring. We used the t test to
      compare the occurrence of desaturation with the pH monitoring parameters. We
      found higher significance with the reflux index (RI), number of episodes longer
      than 5 minutes, ZMD index, 24-hour mean pH, and mean pH of desaturation. The
      bivariate analysis, taking into account possible confounding factors and RI,
      showed PR equal to 6.61 (IC 95% 1.67 - 26.12) for an RI higher than 4%.
      CONCLUSION: Oxygen saturation monitoring associated with pH monitoring may be a
      useful tool to establish an association between GER and respiratory problems in
      patients with chronic or recurrent wheeze.

PMID- 14647598
TI  - [Overweight and obesity prevalence in children and adolescents from a private
      school in Recife]
AB  - OBJECTIVES: To determine the prevalence of overweight and obesity in students
      from a private school in Recife; compare the prevalence rates of overweight and
      obesity in boys and girls and in different age groups (children and adolescents)
      and verify the correlation between body mass index and triceps skinfold thickness
      in this population. METHODS: Cross-sectional study with 762 students (332
      children and 430 adolescents) from a middle/upper class school in Recife, in
      1999. Overweight was defined as body mass index equal or above the 85th
      percentile for age and gender. Obesity was defined as body mass index and triceps
      skinfold thickness equal or above the 85th percentile. RESULTS: The prevalence
      rates were 26.2% (95%CI = 23 to 29%) for overweight, and 8.5% (CI95% = 6.5 to
      10.5%) for obesity. Overweight was more prevalent among children (34.3%) than
      among adolescents (20.0%) (P<0.001). Obesity was more frequent among children
      (14.2%) than among adolescents (4.2%) (P<0.001). The prevalence of overweight in
      boys (34.6%) was higher than in girls (20.6%) (P<0.001). The prevalence of
      obesity was also higher in boys (14.7%) than in girls (4.4%) (P<0.001). The
      correlation coefficient between body mass index and triceps skinfold thickness
      was equal to 0.64 (95%CI = 0.60 to 0.68). CONCLUSIONS: The prevalence of
      overweight in our study population was as high as that found in industrialized
      countries; obesity, however, was less frequent.

PMID- 14647599
TI  - [Idiopathic hypercalciuria: presentation of 471 cases]
AB  - OBJECTIVE: To analyze the clinical history and evolution of children and
      adolescents with IH, emphasizing some of their peculiar features. METHODS: We
      followed 471 patients with IH at an outpatient clinic. Patients were submitted to
      the following protocol: abdominal X-ray, kidney and urinary tract
      ultrasonography; urinary ionogram, blood gas and biochemical analyses; 24-hour
      urine for measurement of calcium and other electrolytes and creatinine;
      urinalysis, urine culture and phase-contrast microscopy; second morning urine
      collected after fasting for measurement of calcium and creatinine. RESULTS: At
      the time of diagnosis, 6% of the patients were infants, 15% pre-school children,
      55% school children, and 24% adolescents; 56% of them were boys. Clinical and
      laboratory findings were: 47% had hematuria and abdominal pain, 31% had isolated
      hematuria, 14% isolated abdominal pain, and 8% had urinary tract infection,
      nocturnal enuresis, suprapubic pain or urethralgia, or the frequency/urgency
      syndrome with urinary incontinence. Hypercalciuria was associated with
      urolithiasis in 56% of patients. There was association with hyperuricosuria in
      18.5% of the cases, and hypocitraturia in 8.5% of the cases. Evolution was poor
      for 33% of the patients, with recurrence of nephrolithiasis, persistence of
      hematuria, and abdominal pain. CONCLUSIONS: IH must be diagnosed and treated with
      criteria in order to reduce consequences such as hematuria, abdominal pain,
      urinary stone formation and possible bone involvement. Signs and symptoms such as
      urgency and urinary incontinence, suprapubic pain and nocturnal enuresis may
      result from renal hyperexcretion of calcium.

PMID- 14647600
TI  - [Antistreptolysin O titer profile in acute rheumatic fever diagnosis]
AB  - OBJECTIVE: To determine ASO titer profile by establishing ARF differential
      diagnoses of other diseases with high levels of ASO antibodies. METHODS: We
      investigated 78 patients with ARF at onset and follow-up, 22 with isolated chorea
      at onset, 45 with recurrent oropharyngeal tonsillitis, and 23 with recent flare
      of juvenile idiopathic arthritis. We tested ASO with automated particle-enhanced
      immunonephelometric assay (Behring(R)-Germany). The ASO (IU/ml) titers were
      assessed at the following time intervals: 0-7 days, 1-2 weeks, 2-4 weeks, 1-2
      months, 2-4 months, 4-6 months, 6-12 months, 1-2 years, 2-3 years, 3-4 years, and
      4-5 years after onset of ARF. RESULTS: ASO titers in patients diagnosed with ARF
      had a significant increase up to the 2-4-month time interval (P<0.0001). Baseline
      levels were observed afterwards in patients under regular penicillin prophylaxis.
      The levels of ASO in ARF were also significantly higher than in patients with
      isolated chorea, recurrent oropharyngeal infections or juvenile idiopathic
      arthritis (P=0.0025), when age-matched samples of these groups were compared. The
      testacute;s sensitivity was 73.3% and the specificity was 57.6%, and it was
      calculated taking into account the upper limit of normality at 320 IU/ml, as well
      as the established diagnosis of ARF. The testacute;s specificity and positive
      predictive value increased with rising or higher titers, being higher with titers
      above 960 UI/ml. CONCLUSION: This reappraisal of ASO profile in ARF patients
      indicates a remarkable response during the acute phase, and that points to the
      extent to which ASO levels may differentiate ARF from other diseases with high
      levels of ASO antibodies, as coincidental but unrelated streptococcal infection
      or chronic arthritis flareup.

PMID- 14647601
TI  - [Positive skin test and age]
AB  - OBJECTIVE: To evaluate positive responses to skin tests for immediate
      hypersensitivity to allergens in children with asthma and rhinitis at different
      ages. METHOD: We observed positive skin test reactivity in prick tests using
      fifteen allergens of same origin (total dust and Dermatophagoides sp.;
      Dermatophagoides pteronyssinus; Dermatophagoides farinae; Blomia tropicalis;
      Penicillium sp; Alternaria alternata; Cladosporium herbarium; Aspergillus
      fumigatus; Bermuda grass; forage grass; dog and cat epithelia; feathers; Blatella
      germanica and wool). We placed 713 selected patients into different age groups -
      Group I: 6 to 11 months; Group II: 1 to 3 years and 11 months; Group III: 4 to 8
      years and 11 months; and Group IV: 9 to 15 years. We used the chi-square test for
      statistical analysis. RESULTS: The total significant differences between these
      groups were: I to II = 5; II to III = 5; II to IV = 5; III to IV = 6; I to III =
      10; and I to IV = 10. CONCLUSION: Skin test reactivity is acquired progressively
      with age, and can be observed as early as at 12 months. Reactivity is
      significantly more positive from the age of 4 on.

PMID- 14647602
TI  - [Renal scintigraphy using technetium dimercaptosuccinic acid in the diagnosis of
      pyelonephritis in children: study of 17 cases]
AB  - OBJECTIVE: To determine whether the presence of abnormal results in DMSA renal
      scintigraphy indicates pyelonephritis. METHODS: We performed the washout test in
      17 children with urinary tract infection, as a criterion standard, to locate the
      infection site. All the children underwent DMSA renal scintigraphy in the acute
      phase of the disease. The results were analyzed by the chi-square test or Fisher
      test. RESULTS: DMSA renal scintigraphy revealed changes in all five cases of
      pyelonephritis, suggesting acute kidney involvement. On the other hand, only one
      child with cystitis (total = 12 cases) had abnormal results in renal
      scintigraphy. Sensitivity and specificity were 100% and 92%, respectively.
      CONCLUSION: DMSA renal scintigraphy is a sensitive method for the diagnosis of
      pyelonephritis in children.

PMID- 14647603
TI  - [Hearing evaluation in children aged 3-6 years in day-care centers]
AB  - OBJECTIVE: To estimate the prevalence of deafness in children 3-6 years old in
      day-care centers of Sao Jose do Rio Preto, SP, Brazil. METHODS: We used free
      field audiometry to screen 103 children from 8-selected day-care centers.
      Children with abnormal examination results were referred to the speech therapy
      outpatient service to undergo pure-tone conventional audiometry. We adopted the
      WHO classification for degree of deafness. RESULTS: Audiometric dysfunctions were
      present in 10 children (9.70%; SD=0.96) with one boy showing left ear mild
      conductive hearing loss (mean LE=35 dB), while 9 children (8.73%; SD=2.78) showed
      alterations in air-conduction threshold in 4000, 6000 or 8000 sharp frequencies.
      Out of 102 children (99.03%; SD=0.96), 55 boys (53.39%; SD=4.9) and 47 girls
      (45.64%; SD=4.9) presented no hearing loss according to the WHO criteria.
      CONCLUSIONS: The prevalence of 9.7% audiometric dysfunctions found in this study
      indicates that deafness prevention programs should be organized.

PMID- 14647604
TI  - [Celiac disease: clinical characteristics and methods used in the diagnosis of
      patients registered at the Brazilian Celiac Association]
AB  - OBJECTIVE: To evaluate the clinical characteristics and methods used in the
      diagnosis of patients registered at the Brazilian Celiac Association (BCA).
      METHODS: A questionnaire about clinical characteristics and diagnostic methods in
      celiac disease was mailed to 584 members of the BCA. RESULTS: We received 292
      responses for 584 questionnaires mailed (49.5%). The clinical characteristics of
      celiac disease in the sample we analyzed showed that the most frequent type was
      the classical mode (88.9%), while the atypical mode was present in only 11.1% of
      patients at the time of diagnosis. Increased incidence of both late diagnosed
      classical mode (44.5% to 64.2%; P=.004) and atypical mode (5.2% to 16.8%; P=.005)
      has been observed in the last 5 years. Duration of symptoms before diagnosis was
      greater than 1 year in 75% patients with atypical manifestation. Intestinal
      biopsy was not performed in 19% of the cases at the time of diagnosis. It was
      observed that in the last 5 years intestinal biopsy was not performed for a
      larger number of patients (24.4%) than in the previous period (only 11.1%)
      (P=.007). CONCLUSIONS: Classical mode is still the most frequent clinical
      manifestation of celiac disease. The late diagnosed classical mode is
      predominant, but our findings show an increase in the proportion of the atypical
      mode. Although characterization of subtotal or total villous atrophy of the
      intestinal mucosa is of paramount importance to the diagnosis of celiac disease,
      19% of the patients diagnosed for celiac disease did not undergo intestinal
      biopsy at the time of diagnosis, most notably in the last 5 years.

PMID- 14647605
TI  - [Treatment of lymphangioma with alpha-2a-interferon]
AB  - OBJECTIVE: To describe the results of the use of alpha-2a-interferon in the
      treatment of inoperable childhood lymphangiomas refractory to other therapeutic
      management. METHOD: We reviewed the literature about pathogenic events and the
      treatments available for lymphangiomas. Based on that, we used alpha-2a
      interferon at a dose of 3 million units/m(2)/day administered subcutaneously to
      patients with inoperable disease and no response to other treatments. We
      conducted periodic clinical and laboratory control to evaluate the response and
      the adverse reactions to alpha-2a-interferon administration. RESULTS: We observed
      that the 6 patients with inoperable lymphangiomas who used alpha-2a-interferon
      had a satisfactory clinical response associated with minimum adverse reactions.
      Of these patients, 5 had partial regression of their lesions, and 1 remained
      stable. CONCLUSION: Alpha-2a-interferon may be one more available treatment for
      inoperable childhood lymphangiomas.

PMID- 14647606
TI  - [Exogenous surfactant treatment for severe acute viral bronchiolitis: case
      report]
AB  - OBJECTIVE: To describe the possible clinical and laboratory effects of exogenous
      surfactant instillation into the tracheal tube of a child with severe acute
      bronchiolitis undergoing mechanical ventilation. CASE REPORT: a 2-month-old girl
      with clinical diagnosis of acute viral bronchiolitis underwent mechanical
      ventilation. She required high positive inspiratory peak pressure (35 to 45
      cmH(2)O) and high inspiratory fraction of oxygen (FiO(2) = 0.9), but showed no
      clinical response or improvement in the arterial blood gas analysis. An exogenous
      surfactant (Exosurf(R), Glaxo - 50 mg/kg) was used to facilitate the use of a
      less aggressive ventilatory strategy. RESULTS: Four hours after surfactant
      administration, it was possible to reduce the positive peak inspiratory pressure
      (PIP) from 35 to 30 cmH(2)O, and FiO(2) from 0.9 to 0.6; and to increase the
      positive end-expiratory pressure (PEEP) from 6 to 9 cmH(2)O. During this period
      the paO(2)/FiO(2) ratio increased from 120 to 266. At the end of 24 hours, FiO(2)
      could be reduced to 0.4. DISCUSSION: Surfactant inactivation may be a decisive
      factor in the unfavorable evolution of some severe cases of acute bronchiolitis.
      The tracheal instillation of exogenous surfactant, in these cases, allows us to
      adopt less aggressive ventilatory strategies, and promotes rapid clinical
      responses.

PMID- 14647608
TI  - [Eyes on the present and looking into the future]

PMID- 14647607
TI  - [Epidemiology of polydactylies: a case-control study in the population of Pelotas
      RS]
AB  - OBJECTIVE: To identify and compare cases of isolated polydactyly with healthy
      newborns regarding familial and maternal characteristics. METHODS: We conducted
      this hospital-based case-control study from 1990 to 1998. We collected data in
      interviews with mothers of cases and controls during the post-delivery period.
      Cases were defined as newborns presenting an extra or a bifid digit in hands
      and/or feet. Controls were the four healthy newborns that were born after the
      case, at the same hospital. Information was gathered on type of polydactyly,
      gender and birthweight, twin pregnancy, parental consanguinity, ethnicity.
      RESULTS: African ancestry and positive family history of congenital malformation,
      especially polydactyly, were significantly associated with the occurrence of this
      type of congenital anomaly (crude OR of 3.3; 10.0; and 55.0, respectively).
      CONCLUSION: Isolated polydactyly was one of the most frequent malformations found
      in the studied population. The findings associated with black African ancestry
      confirm the data presented in the literature. Studies conducted on this same
      population, with a larger population of patients with this type of malformation,
      could investigate this association better and justify the results presented here.

PMID- 14647609
TI  - [Diabetic ketoacidosis - revisiting the basic concepts]

PMID- 14647610
TI  - [The growth of native Brazilian Indian children]

PMID- 14647611
TI  - [Maternal periodontal disease and premature birth or low birth weight]

PMID- 14647612
TI  - [Sudden infant death syndrome]

PMID- 14647613
TI  - [Diabetic ketoacidosis in children: review of pathophysiology and treatment with
      the use of the "two bags system"]
AB  - OBJECTIVES: To review diabetic ketoacidosis, including the "two bags system", a
      method of administering liquids in order to provide a smoother correction of the
      hyperglycemic and ketotic states. METHODS: Review of recent publications (last 7
      years) from a Medline search and chapters published in pediatric textbooks that
      discuss the etiology, therapy, and complications of diabetic ketoacidosis. The
      management approach incorporates the findings of these publications as well as
      the clinical experience at the Childrens Hospital of Philadelphia and Duke
      University Medical Center. RESULTS: The pathology of the type 1 Diabetes Mellitus
      involves the progressive destruction of the ss cells of the pancreas, causing
      insulin deficiency. Insulin is essential in the metabolism of carbohydrates,
      protein and fat. Insulin deficiency may lead to diabetic ketoacidosis which has
      three components: 1) hyperglycemia, which causes glycosuria and consequently
      dehydration; 2) lipolysis which, causes ketonemia/ketonuria; and 3) acidosis,
      that is caused by the dehydration and the high serum levels of ketones. Diabetic
      ketoacidosis is a serious condition and, if not treated appropriately, can cause
      coma and death. In children cerebral edema is the major complication of the
      therapy for diabetic ketoacidosis. Careful replacement of insulin, fluids,
      glucose and electrolytes is essential. CONCLUSIONS: The literature presents
      different ways to manage DKA in pediatrics, without a consensus on the cause of
      the most important complication (cerebral edema), and consequently without a
      consensus on the best approach. The use of the two saline bags in patients in DKA
      allows fast adjustments in the dextrose concentration of the infusion fluids,
      simplifying and reducing the costs of the treatment of diabetic ketoacidosis.

PMID- 14647614
TI  - [Physical growth of five to ten year old Xavante indian children in Mato Grosso]
AB  - OBJECTIVE: To investigate the physical growth of Xavante children aged 5-10 years
      and living at the Sangradouro and sao Marcos reservations, state of Mato Grosso,
      central Brazil. METHODS: A cross-sectional survey was carried out in February
      1997 in two native Brazilian Indian schools. Our sample included 233 children.
      The following data were collected: birth date, sex, weight, height, arm-muscle
      circumference, and triceps skinfold thickness. Data on height and weight were
      compared to National Center for Health Statistics (NCHS) growth charts following
      the recommendation of the World Health Organization. RESULTS: Our results show
      that 9% of our population sample had height-for-age Z scores <-2. For boys,
      statistically significant differences (P<0.05) in height-for-age and weight-for
      age Z scores were observed between the two communities. Similar differences were
      not observed for girls. Xavante children are, in average, shorter in height than
      North-American children. However, for some age groups, the average values of
      height overlap with those of the Brazilian children investigated by the National
      Research on Health and Nutrition (PNSN). CONCLUSIONS: The physical growth profile
      of Xavante children presented important differences when compared to that of a
      number of other South American native Indian populations. Based on the
      information collected, we argue that North-American curves can be used to
      evaluate the nutritional status of Xavante children.

PMID- 14647615
TI  - [Periodontal disease in pregnancy and low birth weight]
AB  - OBJECTIVE: Recently, it has been suggested that periodontal disease during
      pregnancy could have a causal relationship with low weight at birth. Our
      objective was to evaluate the influence of periodontal disease during pregnancy
      on the birth weight of newborn infants. METHODS: Mothers who gave birth to low
      birth-weight infants were randomly selected (Group 1 - G1; n=13). Immediately
      after inclusion of each mother in group 1, the mother of the next term newborn
      with birth weight of > 2,500 g (Group 2 - G2; n=13) was included as control.
      Mothers were examined by a periodontist who was not informed of the group the
      child belonged to. A probe was used to measure attachment loss of the alveolar
      bone. The extension index (EI) and severity index (SI) of the periodontal disease
      were determined. RESULTS: Both groups of mothers were similar in terms of
      maternal age, parity, color of skin, height, nutrition, smoking, drinking,
      socioeconomic status, prenatal examinations, premature rupture of membranes,
      chorioamnionitis, bacteriuria, placenta previa, abruptio placentae, previous
      hypertensive disease, preeclampsia, and heart disease. The characteristics of the
      newborns were: birth weight - G1 = 1,804 -/+ 675 g x G2 = 3,030 -/+ 516 g;
      gestational age - G1 = 33 -/+ 5 weeks x G2 = 39 -/+ 2 weeks; length of stay in
      the neonatal intensive care unit (NICU) - G1 = 128 days x G2 = 0 days. Average
      EI: G1 = 89.788 -/+ 18.355 x G2 = 72.420 -/+ 20.717; p=0.033. Average SI: G1 =
      1.377 -/+ 0.626 x G2 = 0.754 -/+ 0.413 (OR=18.3; CI95%: 2.5-133.3; p = 0.006).
      After adjustment for risk factors for low birth weight, such as smoking, maternal
      height, bacteriuria, and previous hypertension, the odds ratio for SI dropped to
      7.2 (CI95% = 0.4-125.4; P = 0.176). CONCLUSION: The multivariate analysis
      indicated a marked association between periodontal disease measured by SI score
      and low birth weight. Our data suggested that periodontal disease during
      pregnancy may be a risk factor for low weight at birth.

PMID- 14647616
TI  - [Sudden infant death syndrome: clinical aspects of an underdiagnosed disease]
AB  - OBJECTIVES: To investigate the socio-epidemiologic characteristics of the victims
      of sudden infant death syndrome and to calculate its prevalence during the 1st
      year of life. METHODS: This is an observational, retrospective, and descriptive
      study based on the review of autopsy protocols and questionnaires applied to
      families that had cases of infants death during 1997 and 1998 in the city of
      Porto Alegre. RESULTS: From 335 infants who died, 21 were fulfilled SIDS
      criteria, although SIDS was not recorded as a cause of death on the death
      certificate. The infants had no previous apnea or acute disease that could
      justify the death. Death occurred predominantly in cold months (winter and
      autumn). None of the infants who died slept in supine position. Families had a
      low monthly income (3 minimum wages). Seventy one per cent the mothers were
      smokers and 42% used alcohol during the pregnancy. SIDS prevalence was estimated
      as 6.3% from the total number of deaths, and the specific mortality coefficient
      for SIDS was 4.5:10,000 live births. CONCLUSIONS: The profile identified for
      infants at risk is similar to that reported in the literature. However, since
      SIDS is often misdiagnosed in our community, it does not appear in the statistics
      about infant mortality. As a consequence, there have never been campaigns to
      reduce the risk of death due to this syndrome.

PMID- 14647617
TI  - [Physical abuse: the profile of aggressor and child victim]
AB  - OBJECTIVE: To establish the profile of children who suffer abuse and of abuse
      perpetrators. METHODS: 225 cases of confirmed child-abuse in Curitiba, state of
      Parana, were studied in 1998 based on information collected using a protocol.
      RESULTS: The following patterns were observed: 56% of the children were in school
      age; 59.6% were the first child of the couple; 84.4% were natural offspring; and
      71.1% of the children had a satisfactory school record. Multiple injuries (38.2%)
      were found on the victims bodies, mostly bruises (37.8%). The main aggressor was
      the mother (42.2%); 25.8% of them said that the reason for the violence was
      disciplining the child; 72% of the mothers denied the use of alcohol. CONCLUSION:
      Our results reveal that the children who are most affected by physical abuse are
      the first-borns of married couples, with age between 5 and 11 years; their
      schooling level is compatible with their age. Most violent acts are performed by
      the mother, who hits the child leaving bruises on several parts of the
      victimacute;s body, with the objective of educating, or setting limits to the
      child.

PMID- 14647618
TI  - [Glicemic control in prepubertal and pubertal patients with diabetes type 1 - a
      one year ambulatory follow-up]
AB  - OBJECTIVE: To evaluate glycemic control in type 1 diabetes mellitus patients
      followed in 1998. PATIENTS AND METHODS: We studied 38 patients [22 males; age =
      10.4 -/+ 4.1 years; 12 (31.6%) prepubertal, 26 (68.4%) pubertal], with diabetes
      duration of 3.7-/+3.4 years and age of diagnosis of 7.2 -/+ 4.7 years. HbA1c was
      determined using high-performance liquid chromatography (L-9100 Merck Hitachi,
      reference value =2.6 to 6.2%). RESULTS: HbA1c was 8.04 -/+ 2.4%, without
      association with gender and puberty. In the 27 patients with at least two HbA1c
      determinations, the level of glycemic control changed in 8 (29.6%) and remained
      the same in 19 (70.4%). From these, glycemic control was poor in 3 (11.1%) and
      good in 16 (59.3%). Among the patients with good glycemic control, HbA1c was
      always within reference values in 4 (25%); 7 (43.75%) had at least one HbA1c
      measurement within these limits; and in 5 (31.25%), all HbA1c measurements were
      above the upper limit of the reference range. There was no association between
      the last glycemic control evaluation and the number of HbA1c determinations. The
      intraindividual coefficient of variation of HbA1c in the group that had at least
      three HbA1c determinations (n = 19) was 11.2 -/+ 5.6% (P = 0.0000). CONCLUSION:
      In our study, although most patients presented satisfactory glycemic control
      during the follow-up period, only 4 patients (14.8%) maintained normal values of
      HbA1c. The variability of HbA1c must be evaluated when considering the
      interrelation between glycemic control and evolution to microvascular
      complications in diabetis.

PMID- 14647619
TI  - [Thyroid carcinoma in children and adolescents - review of six cases]
AB  - OBJECTIVE: Childhood thyroid carcinoma is a rare entity whose management is
      controversial. The objective of the present study was to evaluate the
      characteristics of these patients in terms of diagnosis and evolution. PATIENT
      AND METHODS: The evolution of six patients with thyroid cancer, followed at a
      Pediatric Endocrinology Unit during the past 17 years, was retrospectively
      reviewed. RESULTS: Six female patients with age ranging from 4.5 to 12 years were
      studied. In all 6 cases, thyroid nodules were present on the initial evaluation.
      Ultrasonography and 131I scintigraphy showed solid and cold nodules in four
      patients. Histologic findings indicated four papillary and two follicular
      carcinomas. All patients were submitted to total thyroidectomy; four were
      subsequently submitted to radiodine therapy due to the presence metastases and/or
      residual thyroid tissue. CONCLUSION: Our findings support the notion that
      children and adolescents with thyroid carcinoma have a positive prognosis; no
      cases of death occurred after 17 years of follow-up. Our data are in agreement
      with the literature, which describes low mortality rates for these cases.

PMID- 14647620
TI  - [Primitive neuroectodermal tumor of the kidney in children]
AB  - OBJECTIVES: To characterize primitive neuroectodermal tumor of the kidney as a
      differential diagnosis for Wilms tumor, and to emphasize the severity of the
      disease. METHODS: We report the case of a patient with a diagnosis of primitive
      neuroectodermal tumor of the kidney who underwent nephrectomy and complete tumor
      resection combined with chemotherapy. RESULTS: Initially, the response of the
      patient to treatment was favorable, with a few events associated with
      agranulocytosis resulting from the chemotherapy. Ten months after of the end of
      treatment, the tumor recurred in the paraspinal cervical region. CONCLUSIONS:
      Primitive neuroectodermal tumors involving the kidney are very rare and extremely
      aggressive. In such cases, the pathologist has a major role in establishing a
      final diagnosis through histological and immunohistochemical methods.

PMID- 14647621
TI  - [Pediatric cervicofacial actinomycosis - case report and review of the
      literature]
AB  - OBJECTIVE: To emphasize important features in the diagnosis and monitoring of
      patients with childhood cervical actinomycosis. SUBJECT AND METHODS: We report
      the case of a patient with cervicofacial actinomycosis. We also carried out a
      review of the literature from the past few years (Lilacs and Medline). RESULTS:
      We followed a male patient admitted to the pediatric infectious disease ward.
      Diagnosis was carried out through biopsy of a cervical node and isolation of
      bacteria. Specific penicillin treatment for actinomycosis was administered for 14
      days. Subsequently, we observed remission of the node. The patient was discharged
      from the hospital. At least 6 months of amoxycillin therapy with simultaneous
      outpatient follow-up were recommended. CONCLUSION: Early diagnosis of
      actinomycosis enables appropriate and prompt treatment, thus preventing the
      involvement of other areas such as CNS, face, and neck.

PMID- 14647623
TI  - [Hypomelanosis of Ito - case report]
AB  - OBJECTIVES: The authors report a case of hypomelanosis of Ito (HI), a rare
      neurocutaneous syndrome with neurological and chromosomal alterations associated
      with cutaneous involvement and recurrent pneumonia. CASE REPORT: A male patient,
      age 1 year and 11 months, was admitted with bilateral bronchopneumonia to the Sao
      Vicente de Paulo Hospital. Examination revealed hypochromic maculas on the skin,
      compatible with HI, and a delay in neuropsychomotor development. The patient was
      submitted to incisive biopsy of the abdominal skin lesions, electroencephalogram,
      magnetic resonance, and cytogenetic evaluation. RESULTS: Histology and
      immunohistochemistry evinced absence of melanin and reductio of melanocyte in
      focal areas of the epidermis. The electroencephalogram revealed diffuse cortico
      subcortical dysfunction. Encephalic magnetic resonance imaging was compatible
      with arachnoid cyst in the temporal region. Karyotype showed chromosome mosaicism
      (46, XY) and interstitial deletion of bands 22.2 to 24.4 of the long arm of
      chromosome 10 (25%). CONCLUSIONS: Analysis of skin lesions is important for the
      etiologic definition of neuropediatric disorders.

PMID- 14647622
TI  - [Anhidrotic ectodermal dysplasia syndrome in the neonatal period - case report]
AB  - OBJECTIVE: To describe a rare syndrome affecting children, and to urge
      pediatricians to consider this diagnosis when investigating idiopathic fever in
      neonates. METHODS: We report a case of anhidrotic ectodermal dysplasia syndrome
      in a 10 day old newborn in the neonatal intensive care unit at Hospital Geral de
      Caxias do Sul. The child presented recurrent episodes of fever since the first
      days of life. RESULTS: The patient presented dry mucus, dry skin, and fever. Skin
      biopsy was performed in the childacute;s back. Absence of sweat and sebaceous
      glands as well as hypoplasia of follicular structures were identified. The
      patient is receiving adequate treatment, and is being followed as an outpatient.
      CONCLUSION: Anhidrotic ectodermal dysplasia syndrome is a rare disorder that must
      be considered when investigating newborns with recurrent episodes of fever.
      During the neonatal period, the clinical manifestations of the disease are subtle
      and unspecific. Such findings become more visible after a few months of life.
      There is no definitive treatment for this syndrome.

PMID- 14647624
TI  - [Antituberculosis chemoprophylaxis in children previously vaccinated with BCG:
      indications and questions]

PMID- 14647625
TI  - [Measuring early childhood development in epidemiological studies: underlying
      difficulties]

PMID- 14647626
TI  - [Medical end-of-life decisions - the challenge to adjust laws to ethical demands]

PMID- 14647627
TI  - [Otitis media with effusion: expectant management]
AB  - OBJECTIVE: Despite the fact that chronic otitis media with effusion (OME) is an
      entity with a high prevalence among children, the real effectiveness of most
      treatments in use nowadays has not been completely established. Based on its
      natural course, we defend an expectant management as the initial treatment.
      METHODS: We undertook a review of the available data taking into consideration
      the natural history, epidemiology and therapeutic options for OME. We looked for
      a guideline concerning the best treatment for OME in children. RESULTS: The
      treatment of OME still remains controversial, in spite of many therapeutic
      options. In children, the best management still seems to be the observation,
      probably for a period of three to six months. However, interventionist treatment
      should be done earlier on those patients considered as high risk or in which a
      problem happened with their development, due to hearing loss secondary to OME.
      CONCLUSIONS: The understanding of the several factors involved in the
      pathogenesis of OME, as well as of the features in its evolutive course,
      encourage the idea of a conservative expectant approach at first or up to the
      moment in which an interventionist approach (clinical or surgical) is justified.

PMID- 14647628
TI  - [Antituberculosis chemoprophylaxis in a public hospital - study of 100 children]
AB  - OBJECTIVE: To evaluate recommendations for antituberculosis chemoprophylaxis in
      children according to the guidelines of the National Tuberculosis Control
      Program, and in special situations, as very young children, BCG vaccinated
      children with positive tuberculin skin test and recent or current exposure to
      infected cases. METHODS: A retrospective cross-section study has been made of 100
      children who underwent chemoprophylaxis at a public hospital in Rio de Janeiro.
      Variables analyzed were sex, age, BCG vaccination, nutritional status, tuberculin
      skin test, recent tuberculosis converters, infection source for tuberculosis,
      adherence to prevention, monotherapy failure and isoniazid side effects. RESULTS:
      The case history was made up of 57 males and 43 females, 62% were younger than
      five years of age, there was reference to previous BCG vaccination in 92%,
      malnutrition in 28% and recent tuberculosis converters in 9% of the cases.
      Parents represented 60% of infection source known, there was adherence to
      prevention in 73%, monotherapy failure in 1% and isoniazid side effects in 1% of
      the cases. CONCLUSIONS: It has been concluded that 15% followed the Health
      Department guidelines thoroughly, which included the 9 cases of recent
      tuberculosis converters; 85% of the recommended chemoprophylaxis were due to the
      coverage of high-risk groups to develop the disease.

PMID- 14647629
TI  - [Risk factors for suspicion of developmental delays at 12 months of age]
AB  - OBJECTIVE: To investigate the prevalence of positive screening test for
      developmental delays in a cohort of children born in Pelotas, Brazil in 1993, and
      their risk factors. METHODOLOGY: A sample of 20% (1,363 children) of a cohort of
      children born in Pelotas, Brazil, was studied at 12 months of age regarding their
      development. The Denver II Test was used. The children who failed in two or more
      items of the test were suspected of having development delay. A set of
      independent variables was chosen taking into account the hierarchical relations
      between risk factors according to the conceptual framework (socioeconomic,
      reproductive and environmental, birth conditions, childrens care, nutrition and
      morbidity). Analyses were performed using Mantel-Haenszel X2 and multivariate
      technique through conditional logistic regression, to control for possible
      confounding. RESULTS: At 12 months of age, 34% (463) of the total of 1,363
      children failed in the screening test. After adjusting for possible confounding
      variables, failure was associated with family lower income children (OR= 1.5),
      very low birth weight (OR= 4.0), gestational age less than 37 weeks (OR= 1.6),
      more than three siblings (OR= 1.9), and duration of breastfeeding less than three
      months (OR=1.6), or no breastfeeding (OR= 1.9). Children who presented weight/age
      at six months of age less or equal to -2 z score of the reference population
      presented a risk 10 times greater of having failure in the Denver II Test.
      CONCLUSIONS: This study reinforces the multiple etiology of development delays
      and the concept of cumulative risk effect. In this population those who are
      economically disadvantaged accumulate risk factors (social, economic and
      environmental) that may render to deficits in their development.

PMID- 14647630
TI  - [Cardiopulmonary resuscitation: discrepancy between the actual cardiopulmonary
      resuscitation and the documentation in the medical record]
AB  - OBJECTIVES: To describe the characteristics of the patients not resuscitated in a
      university affiliated pediatric hospital. To characterize the data registered in
      the chart regarding the resuscitation and evaluate ethical and legal aspects of
      CPR (cardiopulmonary resuscitation). METHODS: Retrospective study of 176 deaths
      that occurred in a one year time period. The chart was reviewed and compared to
      information received directly from the physician that participated in the
      patientacute;s resuscitation. Ethical and legal aspects involved in resuscitation
      efforts were discussed. RESULTS: During the study period 176 deaths occurred. 47
      (26.7%) patients did not receive CPR as reported directly by the physician in
      charge of the patient when the dead occurred. Two patients were excluded, because
      the chart could not be found. Prior to their death, 64.4% (29/45) received
      mechanical ventilatory support and 48.5% (33/45) received inotropic support. 60%
      (27/45) of the deaths occurred in the intensive care unit. The most common
      diagnoses at admission were sepsis in 28% (13/45) and pneumonia with respiratory
      failure in 27% (12/45). The most common underlying medical conditions were
      malignancies in 28.8% (13/45). Of these 45 patients, the medical record about CPR
      was available in 40 charts. It was documented that 11/40 (27.5%) were declared
      dead without resuscitation efforts and in 29/40 (72.5%) the medical record stated
      that CPR was performed without improvement in vital signs. CONCLUSION: There was
      a discrepancy between the actual cardiopulmonary resuscitation efforts and the
      documentation of cardiopulmonary resuscitation in the medical record. This
      behavior may be due to fear of possible legal consequences of not performing
      cardiopulmonary resuscitation. However, in patients with very poor prognosis it
      may be ethically justified to withhold CPR.

PMID- 14647631
TI  - [Aerosol deposition and clinical performance verified with a spacer device made
      in Brazil]
AB  - OBJECTIVE: To assess the lung deposition pattern of radioaerosol and the clinical
      performance of a spacer developed and made in Brazil. METHODS: Qualitative - in a
      patient with cystic fibrosis - and semi-quantitative - in two healthy volunteers 
      assessment of pulmonary deposition of (99)mtechnetium was done using the
      Aerogama Medical oxigen driven nebulizer system attached to the spacer and a gama
      camera (Siemens, model Orbiter) connected to a microcomputer. In the next step,
      clinical assessment was carried out in 50 asthmatic children, aged from four
      months to 13 years old with an acute attack, using conventional doses of
      albuterol through a metered dose inhaler attached to the spacer device. RESULTS:
      Qualitative assessment revealed a lung silhouette comparable with those obtained
      in the inhalation scintigraphy and semiquantitative assessment reveals that 7.5%
      to 8.0% of the inhaled (99m)technetium reached the volunteers lungs.
      Statistically significant differences (p < 0.001) were observed comparing
      clinical scores at admission with those verified 20 and 40 minutes after
      albuterol inhalation; conversely, no significance was obtained for scores taken
      at 60 and 80 minutes. CONCLUSIONS: Although we used an alternative method, the
      scintigraphic assessment reveals an expected pattern of pulmonary deposition.
      Similarly, clinical performance in the treatment of an acute attack showed
      results comparable with those obtained with other spacers devices.

PMID- 14647632
TI  - [Comparison of conductivity with sodium determination in the same sweat sample]
AB  - OBJECTIVE: To correlate sweat conductivity by Wescor with quantitative sodium
      determination in the same sample. METHODS: We analyzed 206 sweat samples, being
      31 obtained from patients with cystic fibrosis (CF). Sweat was collected by
      quantitative pilocarpine iontophoresis in the Macroduct system for 30 minutes.
      Samples were immediately determined by Sweat-Chek analyzer (Wescor) and sodium
      quantification with a flame photometer. RESULTS: In non-CF subjects sweat
      (n=175), mean conductivity and quantitative sodium were 41mmol/L (16-75mmol/l)
      and 36mEq/ l (12-75mEq/l) respectively. In CF subjects (n=31), mean values of
      conductivity and sodium were 119mmol/L (84-155mmol/l) and 113mEq/l (80 -
      146mEq/l) respectively. None of CF patients showed values lower than 80mmol/L.
      There was a correlation between sweat conductivity and sodium determination (r= +
      0.99; p<0.0001). CONCLUSION: Sweat conductivity by Wescor simplifies the analysis
      with lower volumes and is well correlated to sodium concentration.

PMID- 14647633
TI  - [Accuracy of MiniWright peak expiratory flow meters]
AB  - OBJECTIVE: To evaluate the accuracy of the Mini-Wright (Clement Clarke
      International Ltd.) peak-flow meters. METHODS: Twenty of those meters were
      checked by use of electronic calibration syringe (Jones Flow-Volume
      Calibrator(R)). Nine of them had an old scale, with values displayed
      equidistantly, and eleven had a new mechanical scale with non-equidistant values.
      Each device was connected in series to the calibration syringe to perform eight
      hand-driven volume injections, with flows ranging from 100 to 700 l/min. Absolute
      and relative differences between meters and syringe were calculated, the syringe
      values taken as standard. The accuracy of the twenty Mini-Wright devices was
      validated by the American Thoracic Society criteria (-/+ 10% or -/+ 20 l/min),
      and/or European Respiratory Society criteria (-/+ 5% or -/+ 5 l/ min). RESULTS:
      New scale instruments were more accurate than old scale meters (p < 0.001), by
      both ATS and ERS criteria. Every meter was rechecked after 600 measurements. Both
      the old, and the new scale instruments maintained the same level of performance
      after this evaluation. CONCLUSIONS: Results suggest that new scale meters were
      accurate and can be safely used in clinical practice. The authors strongly
      recommend that they are rechecked regularly to ensure that they are within the
      ATS and ERS variation limits.

PMID- 14647634
TI  - [Chronic intestinal pseudo-obstruction in children - report of seven cases]
AB  - OBJECTIVE: The purpose of this report is to describe the clinical characteristics
      and histological abnormalities on full-thickness intestinal biopsy in seven
      children from the Gastroenterology (GI) outpatient clinic. METHODS: A
      retrospective study of all patients who attended the GI outpatient clinic in the
      last ten years. The medical records of seven patients were reviewed, and all the
      relevant clinical data recorded. Diagnosis was based on clinical, laboratorial,
      and histological findings. CONCLUSION: Although this is a rare syndrome, the
      differential diagnosis shall be performed whenever the patient presents signs and
      symptoms of obstruction along the digestive tract with no association of any
      mechanical cause. Studies shall be encouraged regarding the precocious and
      accurate diagnosis, using less invasive techniques and specific therapeutics
      (both clinical and surgical), in order to improve life quality and extended
      survival of affected patients.

PMID- 14647635
TI  - [Aplastic crisis in sickle cell anemia induced by parvovirus B19]
AB  - PURPOSE: Transient aplastic crisis is reported in an eight-month old child with
      sickle cell anemia and acute B19 parvovirus infection. This fact is uncommon in
      this age. PATIENT AND METHODS: The authors review the literature and describe a
      clinical case of an eight-month old child with sickle cell anemia presented with
      profound anemia and reticulocytopenia. His peripheral blood was analyzed for
      parvovirus B19 using the polymerase chain reaction (PCR), and for anti B19
      immunoglobulin Ig M, and Ig G by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: An eight-month old child with sickle cell anemia was admitted to the
      hospital with fever and profound anemia (HB = 3.8g/ dl) and reticulocytopenia
      (2%). A diagnosis of aplastic crisis was established. The results indicate that
      Ig M and PCR were positive and Ig G negative. The patient needed erytrocyte
      transfusion, and was discharged on hospital day 4. CONCLUSIONS: The clinical and
      laboratory features indicate that human parvovirus B19 was the etiologic agent of
      an aplastic crisis in an eight-month old child. According to the international
      literature this event is uncommon for this age; in addition, this is the first
      time it appears in the Brazilian literature.

PMID- 14647636
TI  - [Congenital syphilis: an emerging emergency also in Brazil]
AB  - OBJECTIVE: To highlight to the fact that some newborns are not identified as
      having congenital syphilis, and will present to an emergency room within a few
      months with a severe disease. METHOD: Review of the charts concerning 3 patients
      with congenital syphilis, as well as review of the literature using Medline and
      Lilacs databases, covering the period from 1988 to 1999. RESULTS: We describe the
      case of 3 infants whose diagnosis of congenital syphilis was only established
      after the neonatal period, when they presented to the emergency room and were
      admitted to the pediatric intensive care unit. The first patient had
      neurosyphilis and nephrotic syndrome, the second had neurosyphilis, and the third
      had hepatitis. We discuss the clinical aspects of the cases, and comment on other
      clinical manifestations of congenital syphilis that should be within the purview
      of pediatric emergency medicine. We analyze the reasons for the failure to
      diagnose syphilis at birth, and describe some risk factors for gestational
      syphilis. CONCLUSIONS: Considering the rising incidence of syphilis in Brazil,
      and the possibility that the congenital infections are not recognized at birth,
      emergency physicians must keep a high degree of suspicion and an awareness of
      maternal risk factors, prenatal serology pitfalls, as well as of the several
      clinical presentations of congenital syphilis that can develop in the first
      months of life.

PMID- 14647638
TI  - [The role of the preceptor in medical residencies in Pediatrics]

PMID- 14647637
TI  - [Appendicitis in the premature newborn]
AB  - OBJECTIVE: To present a case of acute appendicitis in a premature infant.
      METHODS: Retrospective review of the literature using Medline and Lilacs
      databases, as well as the necropsy report. CLINICAL REPORT: A white male preterm
      infant born at 34 weeks of gestation weighing 1,750g to a primiparous mother. The
      Apgar score was 4 and 8 at 1st and 5th minutes, respectively. The physical exam
      was normal until the 9th day of life when the child developed clinical features
      suggestive of acute abdomen, possibly due to necrotizing enterocolitis with
      perforation. He was submitted to exploratory laparotomy, which leaded to the
      diagnostic of acute appendicitis. CONCLUSION: Acute appendicitis must be
      discarded on the differential diagnostic when there is a suspicion of necrotizing
      enterocolitis with perforation, and risk factors are not present.

PMID- 14647639
TI  - [CPAP during neonatal mechanical ventilation]

PMID- 14647640
TI  - [High frequency oscillatory ventilation: small volumes, great expectations]

PMID- 14647641
TI  - [The preceptor in medical residencies in Pediatrics: main attributes]
AB  - OBJECTIVE: To analyze the profile of the preceptors and the attributes they
      consider important for the exercise of that activity, in two medical residency
      programs in Pediatrics in Rio de Janeiro METHODS: Through a questionnaire
      answered by each of the preceptors in two medical residency programs in
      Pediatrics in Rio de Janeiro, one of them connected to a university and the other
      one not, information was obtained on gender, age, time since graduation, how long
      they have been acting as preceptors, graduation titles, specific teaching
      training, and the listing of up to five attributes believed to be necessary to a
      good preceptor. The results were consolidated and discussed in the text. RESULTS:
      Of the 90 participants, 70% were woman, 74% were between 30 and 49 years old, 87%
      graduated between 10 and 29 years ago. Half of them said they did not have any
      specific teaching training and the other half had attended courses on Medical
      Pedagogy and Special Didactics during their respective graduate studies. The
      attribute categories most frequently mentioned were the exercise of tutorship,
      Ethics and Humanism, mastery of the subject area, capacity of permanent
      education, and didactic abilities. CONCLUSION: The preceptors pointed to the
      challenge of exercising preceptorship based on a medical practice where
      professional responsibilities, human relationship, organizational skills,
      evaluation techniques, and mastery of the subject area make the main guiding axes
      of the practice itself. To these axes they added the ethical and humanistic
      aspects and their permanent education capacities. They feel, however, the need
      for a didactic qualification in order to accomplish their duties.

PMID- 14647642
TI  - [Clinical and laboratorial repercussions of the nasal CPAP in preterm newborns]
AB  - OBJECTIVE: Evaluate the efficacy and problems associated with nasal CPAP use.
      METHODS: 96 preterm newborns needing nasal CPAP either as initial ventilatory
      support or as weaning from the ventilator were studied prospectively. RESULTS:
      Nasal CPAP was used in children weighing 480g to 2,450g and corrected gestational
      age of 24 to 39 weeks. It was indicated in cases of apnea (12.5%), hyaline
      membrane disease (32.3%), pneumonia (4.2%), transient tachypnea (22%), and
      weaning from the ventilator (29%). The last indication was more frequent in
      children with lower weight (p<0.01). The median time in nasal CPAP was 60.3h.
      After CPAP installation, there was a significant improvement in the respiratory
      distress that was not shown in the blood gases analysis. The percentage of
      children with nasal hyperemia, nasal bleeding, abdominal distention and children
      that could be fed was directly proportional to how long they had been in nasal
      CPAP. Children weighting </= 1,000g had higher incidence of abdominal distention
      (p<0.01) and those with weight between 1,500 to 2,500g faced higher difficulty to
      be maintained on nasal CPAP (p=0.04). Therapeutic success was of 37% for children
      weighing </=1,000g, 59% for the ones weighing 1,000 to 1,500g, and 83% for those
      weighing 1,500 to 2,500g. CONCLUSIONS: Nasal CPAP is a good option for
      ventilatory assistance in preterm babies. It is a safe therapy which in general
      has only topic complications; it does not prevent patients from being fed during
      its use. Furthermore, it was successful in 59% of the studied patients. do CPAP
      nasal.

PMID- 14647643
TI  - [High frequency oscillation ventilation compared to conventional mechanical
      ventilation plus exogenous surfactant replacement in rabbits]
AB  - OBJECTIVES: (a) to evaluate the effect on oxygenation and ventilation of rabbits
      with induced surfactant depletion when they are submitted to a conventional
      mechanical ventilation, plus a small dose of exogenous surfactant; (b) to compare
      this group with another group submitted to a High Frequency Oscillation (HFO)
      without exogenous surfactant administration.METHODS: Twenty New Zealand White
      rabbits weighing (-/+ 3 kg) were anaesthetized and artificially induced to a
      endogenous surfactant depletion by successively lung lavage with normal saline
      (aliquots of 25 ml/kg) until to reach a persistent PaO(2) less than 100 mmHg when
      submitted to a mechanical ventilation in a pressure control mode with a target
      tidal volume of 10ml/kg, PEEP of 5cm H(2)O, FiO(2) 1.0, respiratory rate 30/min,
      and inspiratory time of 0.65 s. Then the rabbits were divided in (a) CMV+S group,
      submitted to a conventional mechanical ventilation plus exogenous surfactant
      replacement; (b) HFO group, submitted to a High Frequency Oscillation
      Ventilation. Arterial blood gases were measured at control period, post lung
      lavage, 15, 16 and 120 minutes after treatment started. The groups were compared
      using Student t test.RESULTS: The post lung lavage PaO(2) in both groups was
      lower than 50mmHg (p=0.154), increasing after 15 min of treatment to 254 mmHg
      (CMV+S) and 288 mmHg (HFO, p=0.626). The PaO(2) at 60 and 120 minutes were higher
      (p=0.001) in the HFO group (431 e 431 mmHg) when compared with the CMV+S group,
      which showed a progressive fall (148 e 126 mmHg). At 60 minutes of treatment, the
      PaCO(2) was lower (p=0.008) in the CMV+S group (29 versus 41 mmHg).CONCLUSIONS:
      In ARDS animal model a protect mechanical ventilation strategy as HFO by itself
      promotes a fast and persistent increase in the oxygenation, with superior levels
      than those observed in animals treated with conventional mechanical ventilation
      plus exogenous surfactant replacement.

PMID- 14647644
TI  - [Effect of in-home boiling and refrigeration on bacterial load of pasteurized
      milk]
AB  - OBJECTIVES: To assess the efficacy of in-home boiling of pasteurized milk in
      reducing the bacterial load and the ability of the refrigeration in preserving
      the milk after boiling.METHODS: Thirty samples of pasteurized milk bought in Sao
      Paulo, Brazil, were submitted to in-home boiling procedure at the laboratory.
      Portions of samples were taken before and after boiling, and after 2, 4, 6 and 24
      hours under refrigeration for microbiological analyses. Methods used were
      mesophilic bacteria count, and coliforms and Escherichia coli (E.coli)
      enumeration.RESULTS: No sample presented mesophilic bacteria count above the
      Brazilian standard for pasteurized milk. E.coli was not recovered from any
      sample. Ten samples (33%) had coliform bacteria; of these, 3 samples (10%) were
      above the standard. Mesophilic bacteria count after boiling was significantly
      lower than before boiling. After 24 hours under refrigeration, mesophilic
      bacteria count was significantly higher than after boiling. No significant
      differences were found between the intervals of 2, 4, 6 and 24 hours under
      refrigeration. Samples before boiling presented significantly higher coliform
      bacteria. No coliform bacteria were recovered at any time after
      boiling.CONCLUSIONS: In-home boiling of milk reduced bacterial load, while
      refrigeration kept bacteria under low counts.

PMID- 14647645
TI  - [Association of signs and symptoms with cerebral neoplasms in infancy]
AB  - OBJECTIVE: To validate groups of cerebral neoplasia symptoms/signs capable of
      performing diagnosis of children with neoplasia, with a higher reliability.
      METHODS: Cross-sectional survey, clinical-epidemiological, and double-blind
      survey for cerebral neoplasia diagnosis based on data from encephalic and cranial
      computered tomography scanning (ECCT) and/or magnetic resonance imaging (MRI)
      services in the state of Bahia, first semester of 1995. A total of 753 children
      from 1 to 15 years of age, with exams and information regarding symptoms/signs
      were included. These were classified in 4 groups (1 to 4), according to location
      of the cerebral tumor. The ECCT and/or MRI were the gold standard and independent
      evaluation for each group. Basic calculation: sensibility, specificity, negative
      and positive predictive values (PPV), accuracy, pretest prevalence, and
      confidence interval (CI) at 95%. Complementary: Bias, odd ratio (OR), prevalence
      ratio (PR) and Kappa (k) with qualification of validation. RESULTS: 34 cases of
      tumors were detected, with the loss of one; prevalence of 4,4%. Evaluation
      results >/= 90% for group 2 symptoms/signs (ataxia and/or cranial nerves palsy),
      except PPV = 82%; elevated k, and "optimal" evaluation. It was the best tumor
      predictive group. The prevalence CI was significant, with small amplitudes. Group
      3 (endocrine/visual dysfunction), was optimal for k, but with a lower PPV.
      CONCLUSION: Symptoms/signs of group 2 are important for cerebral tumor diagnosis,
      followed by group 3. A complete anamneses and neurological examination of
      children with cephalea and/or seizures are important for screening and reference
      to bioimaging services. High number of normal exams increases assistance costs,
      becoming a negative factor for children who really need the exams.

PMID- 14647646
TI  - [Accidents with children in the region of Campinas, Brazil]
AB  - OBJECTIVE: Evaluate prospectively the frequency and cause of accidents in
      children seen at the Pediatric Emergency Service of a University Hospital. The
      main aim is to subsidize the development of education and preventive
      programs.METHODS: Data of all children, less than 14 years old, from March 1997
      to February 1998 were collected with a standard questionnaire.RESULTS: Accidents
      in 3,214 children were studied, 11.4% of the total. Males predominated (62.1%).
      Accidents were more common in the 9 to 13 year age group (33.4%), 2 to 5 year age
      group (27.2%) and 5 to 9 year group (25,5%). Traumatism, mainly due to falls, was
      the cause in 74%. Head trauma was important in the younger than 1 year, and
      trauma involving the extremities in the 9 to 13 age group. Bites and stings
      predominated in the 5 to 13 year age group, intoxication and foreign bodies in
      the 2 to 5 years age group. Burns predominated in the younger than 5 years. Most
      accidents (89.7%) were of low complexity but 20 patients had to be admitted to an
      ICU and 4 died in the Emergency Room.CONCLUSIONS: The child older than 9 years,
      male, with trauma of the extremities due to a fall was the most frequent case of
      accident. Prevention programs must be targeted to specific age ranges. Accidents
      are responsible for a great part of the overload of Emergency Services as 89.7%
      were of low complexity. Primary care health facilities personnel must be trained
      to manage accidents that do not involve complex procedures.

PMID- 14647647
TI  - [Application of a clinical and laboratory protocol for the investigation of
      inborn errors of metabolism among critically ill children]
AB  - OBJECTIVE: The aim of this work was to evaluate a protocol for investigation of
      Inborn Errors of Metabolism (IEM) in children who are acutely ill.METHODS: Forty
      six children with clinical suspicion of a metabolic disorder were studied during
      2 years. They were selected through request for investigation of IEM from
      Pediatrics or Neonatal Intensive Care Units located in the metropolitan area of
      Porto Alegre. Criteria for inclusion were presence of one or more of the
      following clinical alterations, without defined etiology: Metabolic acidosis,
      electrolyte disturbances, hypoglycemia, seizures, lethargy, liver disfunction,
      family history suggestive of IEM. The protocol included clinical evaluation,
      compulsory tests (performed in all patients) and optional tests (performed
      selectively according to the results from the first tests or through specific
      clinical hypothesis).RESULTS: Six cases of IEM were identified: galactosemia, non
      ketotic hyperglycinaemia, propionic acidemia, isovaleric acidemia, 3-hydroxy-3
      methylglutaric acidemia and deficiency of 3-ketothiolase deficiency.CONCLUSIONS:
      The frequency of organic acidurias in this group was 4/46 (8.7%), which justifies
      the inclusion of organic acids analysis among the first line exams in acutely and
      severely ill children with undefined etiology. The relatively high frequency of
      IEM (6/46 or 13%), which is comparable to the ones observed in other studies
      within high risk groups, indicates that the protocol suggested is efficient and
      justifies the systematic investigation of IEM in not explained critically ill
      children.

PMID- 14647648
TI  - [Diabetes insipidus as an early clinical manifestation of pineal tumor]
AB  - OBJECTIVE: To present a pineal tumor diagnosed after long clinical course of
      diabetes insipidus.CASE REPORT: A ten years old male patient, with symptoms of
      polyuria, polydipsia and nocturia for 18 months was admitted at the Nephrology
      Unit with the diagnosis of nephrogenic diabetes insipidus. Six months prior to
      his admission, he had been submitted to a computed tomography scan, which was
      considered inconclusive. The diagnosis of central diabetes insipidus was
      confirmed by a water deprivation test. A head magnetic resonance imaging
      demonstrated two masses suggesting germinoma.CONCLUSIONS: Our observations show
      that patients with central diabetes insipidus need close clinical, laboratory and
      neuroradiological follow-up in order to detect the intracranially tumors in an
      early stage.

PMID- 14647649
TI  - [Intensive phototherapy treatment for severe haemolytic disease of the newborn]
AB  - OBJECTIVE: To discuss the use of alternative treatment methods in hemolytic
      disease of newborn to replace common early exchange transfusion. METHODS: Case
      report of newborn with intensive Rh incompatibility treated with intensive
      phototherapy, plus phenobarbital instead of traditional early exchange
      transfusion.RESULTS: The neonates cord blood showed 9.2 mg/dL of total bilirubin
      and 39% hematocrit. He was medicated with phenobarbital and intensive
      phototherapy at once. There was a rapid growing hyperbilirubinemia followed by
      stabilization for almost 60 hours with little changes, but without levels that
      justified an exchange transfusion. He became progressively anemic and needed a
      concentrate transfusion. When he was five days old, he was discharged and
      returned to follow-up at the 7th week of life when his bone marrow was beginning
      to recover from anemia.CONCLUSIONS: This case demonstrates that pharmacologic
      agents and intensive phototherapy can be as useful as advantageous in severe
      hemolytic disease of newborn. We should always try to use them before adopting
      more aggressive therapies.

PMID- 14647650
TI  - [Neonatal tetanus]
AB  - OBJECTIVE: Neonatal tetanus is an infection with high mortality, constituting a
      problem in underdeveloped countries, where there is faulty prenatal attendance.
      In spite of this and of the decreasing incidence of the disease in the state of
      Rio Grande do Sul, we report a case of neonatal tetanus identified in 1997.
      METHOD: We interviewed the infantacute;s mother and verified her vaccination
      history. We conducted a clinical examination of the newborn, anaerobic culture of
      umbilical stump and review of medical records. We also reviewed the literature
      and verified the epidemic profile of neonatal tetanus in Rio Grande do
      Sul.RESULTS: Healthy mother, with complete outline of tetanus vaccination 4 years
      ago, prenatal uncomplicated and hospital delivery. Family of good socioeconomic
      level, differing from the other cases notified in the State, in that most did not
      have prenatal care nor hospital delivery. The patient is a boy. In the 24th day
      of life he presented fever, cyanosis, lower and upper limbs muscle hypertonia and
      opisthotonos episodes. An anaerobic culture of the umbilical stump grew
      Clostridium tetani. He was treated with penicillin G, gentamicin, sedation and
      tetanus immunoglobulin. He left hospital in good conditions.CONCLUSIONS: Faulty
      prenatal care in underdeveloped countries is the largest risk factor for high
      incidence of this disease in these areas. However, in pregnant women with good
      socioeconomic level and prenatal care, as in the case described here, this
      diagnosis should not be excluded if there are suggestive signs of it.

PMID- 14647652
TI  - [Nosocomial infection]

PMID- 14647651
TI  - [Thrombocytopenic purpura after hepatitis B vaccine]
AB  - OBJECTIVE: To demonstrate a case of idiopathic thrombocytopenic purpura after
      hepatitis B vaccine and drive attention to this possible relation when other
      causes have been excluded.METHODS: Description of a case of a patient who was 1
      month and 16 days old and presented petechiae and ecchymoses one week before she
      entered the Emergency Room of the Hospital das Clinicas da Universidade de Sao
      Paulo. Other causes beyond Hepatitis B vaccine, received one month before the
      hemorrhagic state, were ruled out with the history and laboratory exams. A review
      of the literature about PTI revealed case reports of the disease connected with
      Hepatitis B vaccine administration.RESULTS: The vaccine was considered the
      probable cause. The child was treated with intravenous immunoglobulin, improving
      from thrombocytopenia after three days, and remaining without symptoms during one
      month of follow up.CONCLUSION: The thrombocytopenic purpura after hepatitis B
      vaccine is a rare event whose causal relation is hard to prove. The diagnosis is
      based on the exclusion of other possible causes, but in this case, the hypothesis
      may be considered since new cases are being reported in the literature.

PMID- 14647653
TI  - [Why cancer must be considered a childhood disease]

PMID- 14647654
TI  - [Inhaled corticosteroids and growth - a review]
AB  - OBJECTIVE: The aim of this review was to evaluate the medical literature in the
      last 10 years regarding the impact of the use of ICS on children and adolescents
      growth.METHODS: literature review.RESULTS: The use of ICS in childhood asthma in
      dosages appropriate to its severity does not seem to impair the adult
      height.CONCLUSIONS: The use of ICS in childhood asthma does not seem to impair
      growth. However, it is prudent to use the lowest possible dose necessary to
      achieve a good clinical control of asthma, as well as to monitor the growth of
      any child/adolescent receiving ICS.

PMID- 14647655
TI  - [Risk factors associated with the acquisition of multiresistant bacteria in a
      pediatric nursery]
AB  - OBJECTIVE: To identify the risk factors in patients who had a multiresistant
      bacteria during their staying in a Pediatric Intensive Care Unit and in a
      pediatric nursery of a tertiary teaching hospital.METHODS: Chart review of the
      patients who stayed in the units from January, 1995 to July, 1997 and had a
      multiresistant microorganism isolated (both infection and colonization). A case
      control study was done using McNemar test for group comparison and using stepwise
      logistic regression to select independent risk factors. The following risk
      factors were tested: prior hospital staying, underlying disease, intensive care
      unit admission, surgical procedure, urinary catheter, central venous line,
      ventilator, prior antibiotic therapy and skin lesion.RESULTS: Among 52 patients,
      66 multiresistant bacteria were identified (among them, 33 were gram-negative
      bacilli and 33 were methicillin-resistant S. aureus). The logistic regression
      analysis of the case-control study identified 2 risk factors: prior antibiotic
      therapy and skin lesion. A single risk factor was indicated for patients with
      gram-negative bacilli. Nevertheless, for patients with methicillin-resistant S.
      aureus, central venous lines and skin lesion were significant.CONCLUSION: Prior
      antibiotic therapy and skin lesion were the factors associated with the
      acquisition of multiresistant bacteria. Besides skin lesion, for oxacilin
      resistant S. aureus colonized patients, central venous catheter use was a risk
      factor. The strategies employed to limit the spread of those bacteria in the
      hospital should consider these three factors.

PMID- 14647656
TI  - [Hodgkins disease in childhood: a sixteen year experience in a single
      institution]
AB  - OBJECTIVES: To report the experience in the treatment of Hodgkins lymphoma in
      children at Hospital das Clinicas, UFMG, Brazil.METHODS: 31 children with
      Hodgkins lymphoma were retrospectively followed up from 1983 to 1999. Fifteen
      children were treated according to HD-85, a protocol based on German-Austrian
      studies; the 16 remaining children were treated otherwise.RESULTS: The age at
      diagnosis varied from 3 to 15 years (median 9 years). There were 28 male
      patients. The follow-up period ranged from 2 months to 16 years (median 3 years
      and 7 months). Mixed cellularity was the predominant (61%) histological subtype;
      58% had advanced disease (stages III or IV) at diagnosis. Staging abdominal
      surgery was necessary in 61%. No reduction in the frequency of staging surgeries
      was observed after starting standardized HD-85 protocol in 1994. Herpes simplex
      and zoster infections were the most common complications. The estimated
      probability of disease-free survival (DFS) was 55.6%-/+11.7% at 5 years. Overall
      survival probability was 96.5%-/+3.5%. No difference in DFS was apparent between
      children treated with HD-85 and those treated otherwise.CONCLUSIONS: The overall
      results in DFS are worse than those reported in the literature. The predominance
      of mixed cellularity subtype, and early age and advanced disease at diagnosis are
      commonly reported in developing countries and do not fully explain the observed
      results. A longer follow-up is necessary to evaluate the influence of treatment
      standardization on the outcome of these children.

PMID- 14647657
TI  - [Systolic and diastolic blood pressure levels of healthy newborn infants]
AB  - OBJECTIVE: To identify normative blood pressure (BP) levels for Brazilian newborn
      infants and to define a cut-off point for high systolic and diastolic BP in this
      population.METHODS: 634 healthy term neonates, aged 12 to 36 hours, who were born
      in the Instituto Materno Infantil de Pernambuco (IMIP) were included in this
      survey. An oscillometric method was used to acess the neonates BP. To identify
      high BP levels the Second Task Force definition was applied.RESULTS AND
      CONCLUSIONS: The normative BP values for the study sample was 82.0 -/+ 7.5 mmHg
      for systolic and 41.7 -/+ 5.8 mmHg for diastolic blood pressure. The cut-off
      points for high blood pressure were >/= 95 mmHg and >/= 52 mmHg for systolic and
      diastolic blood pressure respectively. These results are similar to those
      reported in other surveys done in other countries.

PMID- 14647658
TI  - [Acute dapsone exposure and methemoglobinemia in children: treatment with
      multiple doses of activated charcoal with or without the administration of
      methylene blue]
AB  - OBJECTIVE: To study the changes in methemoglobinemia of 17 children admitted with
      acute exposure to dapsone complicated by a methemoglobin concentration greater
      than 20% of the total hemoglobin. The children were treated with multiple doses
      of activated charcoal with or without the administration of methylene
      blue.PATIENTS AND METHODS: Seventeen patients (ages 1-13 y, median 3 y), were
      admitted 1-72 h after the ingestion of 100-1200 mg (median 350 mg, 10 patients)
      or an unknown amount of dapsone (7 patients). The methemoglobin blood
      concentrations upon admission ranged from 23.5%-49.7% (median 37.8%), and the
      main clinical features were cyanosis (17), tachycardia (17), vomiting (11) and
      tachypnea (8). All of the children received multiple doses of activated charcoal
      orally or via nasogastric tube (1g/kg, 10% solution, 4-6 times/day, 3-16 doses
      with a median of 8 doses). Twelve of the 14 patients with methemoglobin levels
      greater than 30% were also treated with a single dose of methylene blue (1-2%
      solution, 1-2 mg/kg) infused IV over 5 min.RESULTS: There was a progressive
      decrease in the methemoglobin levels after the beginning of both treatments
      (multiple doses of activated charcoal alone or associated with methylene blue),
      and only one dose of methylene blue was necessary. There were no significant
      statistical differences between the results of the two treatments according to
      the time-course decrease in methemoglobinemia (p=0.49 Wilcoxon test).CONCLUSIONS:
      Multiple doses of activated charcoal given when methemoglobin levels were greater
      than 20% can be considered as a possible treatment for pediatric patients, with
      or without the administration of methylene blue, after acute dapsone exposure.

PMID- 14647659
TI  - [Study of lung involvement in patients with cystic fibrosis]
AB  - OBJECTIVE: To characterize the involvement of the respiratory apparatus of
      patients with cystic fibrosis in order to obtain a comprehensive view of their
      pulmonary picture.METHODS: Data were obtained retrospectively from the medical
      records of 16 patients with cystic fibrosis; arterial gas and spirometry data
      were obtained prospectively for the same patients, who were not in an acute
      pulmonary situation. The patients were subjects of both sexes aged 6 years or
      older who were followed up at the Pediatrics Outpatient Clinic of the University
      Hospital, Faculty of Medicine of Ribeirao Preto, USP.RESULTS: Median patient age
      was 114 months (9 years and 6 months) ranging between 72 - 360 months, and 68.75%
      were males. Productive cough was the most frequent symptom observed in 75% of the
      population studied. All patients had positive sputum culture obtained at least
      one year before, with Pseudomonas aeruginosa being detected in 81.25% of the
      cases. Arterial gases revealed some abnormalities in 81.25% of the patients and
      spirometry revealed abnormalities in 56.25%.CONCLUSION: All patients presented at
      least one type of pulmonary alteration. Measurement of arterial gases detected a
      larger number of patients with altered pulmonary function than did spirometry,
      but the two examinations complemented each other for a good evaluation of
      pulmonary function.

PMID- 14647660
TI  - [Rotavirus detection in feces of children with acute diarrhea]
AB  - OBJECTIVE: To determine the prevalence of rotavirus in the etiology of acute
      diarrhea in children from Natal city, RN, Brazil and investigate the existence or
      not of a seasonal distribution of this pathogen in our environment.METHODS: Fecal
      samples from 1,903 children (boys and girls) with ages ranging from 1 month to 10
      years, living in Natal-RN, who presented acute diarrhea episodes in a period from
      January 1996 to December 1998, were analyzed. We searched viral particles
      directly in the feces by a passive agglutination reaction using anti-rotavirus
      specific-group monoclonal antibodies coated latex particles.RESULTS: 151 children
      (7.9%) of the studied population presented a positive reaction, revealing the
      presence of rotavirus particles in feces. Considering, however, only the children
      (ages from 1 to 24 months) who are more susceptible to rotavirus infection, we
      verified that from 1,065 examined children, 136 of them (12.8%) presented
      positive reaction for rotavirus, and the great majority of all children with
      positive reaction (96.3%) had ages ranging from 6 to 24 months. Analysis of the
      distribution of the cases of rotavirus infection in the three year revealed that
      the incidence of infection was higher in July, August, and September.CONCLUSIONS:
      The results indicated rotavirus infections have an important role in the etiology
      of acute diarrhea cases. The majority of the acute diarrhea cases positive for
      rotavirus occurred during the first two years of life, reaching mainly children
      from 6 to 24 months, with the highest incidence of infection during the months of
      July, August, and September.

PMID- 14647661
TI  - [Coffin-Lowry syndrome]
AB  - OBJECTIVE: To promote the diffusion of the knowledge on the Coffin-Lowry syndrome
      and to contribute to the outline of the disease.METHODS: Case report.RESULTS: The
      clinical signs of a patient with the Coffin-Lowry syndrome are described and
      discussed.CONCLUSIONS: The Coffin-Lowry syndrome, a X-linked genetic disease, is
      probably underdiagnosed in Brazil. The typical facies, dental-skeletal anomalies
      and mental retardation suggest the diagnosis, which can be clinically established
      by radiographic study of the hands.

PMID- 14647663
TI  - [Mycoplasma pneumoniae pneumonia: clinical and radiological features]
AB  - OBJECTIVE: To alert about the great variability of clinical and radiological
      features of Mycoplasma pneumoniae pneumonia in pediatric patients. Although it
      has been referred as a prevalent entity in children, its diagnosis is, many
      times, retarded due to the lack of a pattern that can really be considered
      classic.METHODS: The authors present 5 cases of mycoplasma pneumonia in children.
      Diagnostic difficulties, clinical features, radiological findings and evolution
      after treatment are discussed. The cases have their significant peculiarities
      confronted with the findings of medical literature of the last two decades,
      obtained through a bibliographic research in Medline about the subject.RESULTS:
      All the patients were between 6 and 9 years old, characteristically the most
      prevalent age group for this infection. In none of the cases the possibility of
      mycoplasma infection was considered at first. Clinical hypothesis like sinusal
      aspirative pneumonia, tuberculosis, and asthma were initially considered, but
      later on discarded. Except for one, all the other patients referred previous
      treatment with antibiotics. The initial radiological findings were different
      among the cases: bronchopneumonic consolidations, pleural effusion, perihilar
      adenopathy with interstitial infiltrated, and atelectasic areas. After the
      institution of specific therapy, clinical and radiological evolution was
      favorable in all cases.CONCLUSIONS: Mycoplasma pneumoniae pneumonia has a great
      sort of clinical presentations. In the same way the complementary radiological
      investigation may also demonstrate different patterns of presentation. Due to its
      great variability, mycoplasma is not commonly considered as the first diagnosis,
      even though it is a prevalent disease at pediatric age. This may lead to a delay
      in the diagnosis and institution of an appropriate treatment.

PMID- 14647662
TI  - [Magnesium metabolism in chronic primary hypomagnesemia]
AB  - OBJECTIVES: To report three cases of primary hypomagnesemia (PH) with secondary
      hypocalcemia in symptomatic infants, born to consanguineous parents, and to
      present Mg metabolic studies.METHODS: Classic metabolic balances of Mg were
      performed during three consecutive days, using carmin as fecal marker, with and
      without Mg supplementation.RESULTS: The patients (one male) presented, between 15
      and 28 days old, with convulsions and persistent hypocalcemias, which could not
      be controlled with anticonvulsivants and/or intravenous calcium gluconate. After
      diagnostic was established the above symptoms and hypomagnesemia were controlled
      with Mg supplementation. Without supplements, mean daily balances were negative
      or below daily needs, showing final magnesemias lesser than 0.7 mEq/L and
      hypocalcemias about 3 mEq/L. The renal conservation test performed for six days
      after Mg repletion showed at the beginning of the study normal magnesemias (1.4
      to 1.5 mEq/L) decreasing to 0.7 or 0.8 mEq/L in the first 24 hours, indicating
      absence of response from the body stores. Mg total renal excretion was smaller
      than 1 mEq, during six consecutive days, indicating adequate renal Mg
      reabsorption. Intestinal absorption of Mg varied from 6 to 15% of intake. With Mg
      supplementation, daily balances were positive, correcting progressively the serum
      Ca and Mg. The intestinal absorption was greater than 22% of intake in this
      situation.In pacient LPCJ, urinary excretion was 35% of the administered dosis,
      confirming Mg depletion.CONCLUSIONS: Besides confirming specific intestinal
      malabsorption of Mg, adequate renal conservation and an homeostatic extracellular
      defect of Mg were observed, probably caused by an incapacity of mobilization of
      Mg from tissue reserves.

PMID- 14647665
TI  - [Why must early neonatal mortality be reduced in Brazil?]

PMID- 14647666
TI  - [Organ transplantation in childhood: a chimera?]

PMID- 14647664
TI  - [Transient pancytopenia induced by parvovirus B19 in a child with hereditary
      spherocytosis]
AB  - OBJECTIVE: To describe the occurrence of transient pancytopenia induced by
      parvovirus B19 infection in a patient with hereditary hemolytic anemia and to
      discuss the importance of the diagnosis of this pathology.METHODS: Case report of
      a child whose diagnosis was made by polymerase chain reaction (PCR) and serology,
      and review of the literature.CLINICAL REPORT: A twelve year-old male patient with
      hereditary spherocytosis, presenting non-specific symptoms of an infectious
      syndrome followed by severe and transient pancytopenia, whose diagnosis was a
      parvovirus B19 infection.CONCLUSION: The diagnosis of parvovirus infection has a
      particular importance in hematology, especially on some morbid conditions, among
      them the hereditary hemolytic anemias. PCR is useful because of its rapidness and
      sensitivity on the specific diagnosis of this disease.

PMID- 14647667
TI  - [Prenatal exposure to cocaine: review of the neurobehavioral effects]
AB  - OBJECTIVE: To study prenatal cocaine exposure, emphasizing its behavioral
      effects. METHODS: Literature review of the last 15 years, through Medline and
      direct search. RESULTS AND CONCLUSIONS: According to the literature, the
      incidence of prenatal cocaine exposure is up to 15.5%, and its effects on the
      newborn are particularly on the development of the nervous system. Pediatricians
      and sub-specialists must know the consequences of such exposure in order to
      diagnose and affect the prognosis of these children.

PMID- 14647668
TI  - [Bronchiolitis obliterans in children]
AB  - OBJECTIVE: To review the literature on general aspects of bronchiolitis
      obliterans, with emphasis on childhood postinfectious bronchiolitis
      obliterans.METHODS: The most important publications on bronchiolitis obliterans
      were selected, using basically the Medline database (January of 1966 to September
      of 1999).RESULTS: This review is organized as follows: introduction, general
      aspects of bronchiolitis obliterans (terminology, histopathology and
      classification), and postinfectious bronchiolitis obliterans (etiological agents,
      clinical and radiological aspects, diagnosis and investigation, and
      treatment).COMMENTS: Bronchiolitis obliterans is a clinical syndrome wich is more
      common than previously believed in the pediatric population, thus deserving
      pediatricians attention.

PMID- 14647669
TI  - [Assessing the efficacy of the recombinant human granulocyte colony-stimulating
      factor "rhG-CSF" in the treatment of early neonatal sepsis in premature neonates]
AB  - OBJECTIVE: To evaluate the efficacy of the recombinant human granulocyte colony
      stimulating factor (rhG-CSF) in the treatment of early-onset neonatal sepsis
      among premature infants.MATERIALS AND METHODS: A double-blind, randomized,
      placebo-controlled trial was performed among forty-four preterm neonates who had
      "clinical diagnosis" of early-onset sepsis. The treatment group (n=22) received
      10 micro g/kg/d of rhG-CSF, IV once daily for three consecutive days, and the
      placebo group (n=22) received the same volume of a visually-indistinguishable
      vehicle. Prior to the first dose, and prior to the second and third doses, and
      again 10 days after the first dose, we measured tumor necrosis factor-a,
      interleukin-6, granulocyte-macrophagocyte colony-stimulating factor, G-CSF,
      leukocyte count, absolute neutrophil count, immature/total neutrophil ratio,
      platelet count, and hemoglobin concentration. A bone marrow aspiration was
      performed seven days after the first dose, and both the neutrophil storage pool
      (NSP) percent and the NSP/NPP (neutrophil proliferative pool) ratios were
      tabulated.RESULTS: The treatment and placebo groups were of similar gestational
      age (29-/+ 3 vs 31-/+ 3 weeks) and birth weight (1376 -/+ 491 vs 1404 -/+ 508
      grams). They had similar Apgar scores and 24 hour SNAP scores. No deaths occurred
      during the first week of life among the treatment group while three deaths
      occurred in the placebo group. RhG-CSF treatment did not alter the serum
      concentrations of the cytokines measured (except for G-CSF). Serum G-CSF levels,
      blood leukocyte counts, absolute neutrophil counts, NSP percentages, and NSP/NPP
      ratios were higher in the treatment group 24 hours and 72 hours after dosing. The
      occurrence of a subsequent infection over the two week period following dosing
      was significantly lower in the treatment group (n=2) than in the placebo group
      (n=9; p<0.02, RR 0.19 [0.05-0.78]). The overall mortality rate during the entire
      hospitalization was not different between treatment and placebo
      groups.CONCLUSIONS: Administration of rhG-CSF to premature neonates with the
      clinical diagnosis of early-onset sepsis was associated with lower incidence of
      nosocomial infection over the ensuing three weeks period, but it did not change
      the overall mortality rate.

PMID- 14647670
TI  - [Early neonatal mortality in Caxias do Sul: a cohort study]
AB  - OBJECTIVES: To establish the profile of neonates in Caxias do Sul city, and to
      study early neonatal mortality, its causes and related variables.METHODS: This
      cohort study enrolled 5,545 newborns, which were followed up to 7 days after
      birth. The probability of early neonatal mortality was calculated and multiple
      logistic regression was performed to relate all studied variables to the outcome
      of early neonatal death.RESULTS: The observed probability of early neonatal
      mortality was 7.44 per thousand live births. The incidence of premature births
      and low birth weight was 9.4% and 8.1%, respectively. Fifty five percent of the
      neonates were born through cesarean section, which were related to socioeconomic
      and educational level. Previous history of neonatal mortality, maternal age > 35
      years, gestational age, Apgar score < 7, male sex and low birth weight were
      related to early neonatal death. The main cause of death was hyaline membrane
      disease, followed by congenital cardiopaties, extreme preterm and abruptio
      placentae.CONCLUSION: Even though the observed probability of early neonatal
      mortality was low, some deaths may have been avoided if better prenatal and
      delivery care, as well as newborn assistance had been offered.

PMID- 14647671
TI  - [Clinical profile in children under five year old with acute respiratory tract
      infections]
AB  - OBJECTIVE: To describe the clinical and epidemiological profile of acute
      respiratory infections (ARI) in children younger than five years old, of both
      sexes, diagnosed at the University Hospital Julio Muller.METHODS: This is a
      descriptive and cross sectional study. A standard questionnaire was answered by
      the childrens parents, during the period of October/1996 to February/1997. The
      cases were classified according to the Health Ministry criteria in Upper Airway
      Infection (UAI) or Acute Lower Respiratory Infection (ALRI). The following data
      were analyzed: signs and symptoms, clinical diagnosis, socioeconomic variables,
      nutritional appraisal and passive smoking. The data were analyzed with EPI-Info
      6.02b program. The X(2) test was used with confidence interval of 95% (a =
      5%).RESULTS: The ARI prevalence in children under five years was 25.6%. From the
      total number of 491 children, 76.4% (n=375) had UAI and 23.6% (n=116) ALRI. The
      most frequent diagnosis was nasopharyngitis. The most frequent respiratory
      symptoms were nasal discharge (82.1%) and cough (80.4%). Around 6.1% of the total
      number of the cases were due to pneumonia (77.7% of the cases involving
      hospitalization). There were no associations of ARI with children s nutritional
      status, family income or passive smoking. There was statistical association
      between maternal educational status and ALRI (X(2)= 16.57).CONCLUSIONS: The
      findings show that most of the children presented nasopharyngitis (UAI), being
      most of them male. Pneumonia (ALRI) was the main cause of hospitalization. The
      most common symptoms were nasal discharge and cough. Besides, the most important
      risk factor associated was the mothers educational status.

PMID- 14647672
TI  - [Intrauterine and perinatal mortality: comparative analysis of 3,904 necropsies,
      Hospital de Clinicas, Curitiba, from 1960 to 1995]
AB  - OBJECTIVE: To analyze the influence of the perinatal, fetal or maternal
      pathological processes in the induction of intra or extrauterine death as a
      guideline to a better perinatal medical assistance.METHODS: The authors studied
      retrospectively 3,094 consecutive necropsy cases carried out in stillborn fetuses
      (NM) and newborns (ON) in the period between 1960 and 1995 in the SAP of HC,
      Curitiba. The data analyzed included sex, time of gestation and causes of death
      of fetus and newborns. All maternal conditions that might have contributed to
      intra or extrauterine fetal death were also studied.RESULTS: The prevalence of
      intrauterine death due to maternal diseases was two times higher than
      extrauterine. In contrast, the fetal diseases were responsible mainly for
      extrauterine deaths. Primary placental diseases were responsible for 30% of the
      deaths with low time of gestation and 40% of them in the end of gestation. The
      same group of diseases was responsible for only 15-9% of the extrauterine deaths.
      Diseases of labor contributed to 12-20% of deaths after birth while only 7 to 17%
      of intrauterine deaths.CONCLUSION: Necropsy studies contribute to the
      identification of pathologic processes which affect the patients of any medical
      center. If a pregnancy is associated with a certain disease, the epidemiologic
      data of this study can help to identify the period of major risk of death of the
      fetus or newborn.

PMID- 14647673
TI  - [Signs and symptoms associated with chronic constipation]
AB  - OBJECTIVE: To check whether signs and symptoms referred to by parents are
      associated with chronic constipation. METHODS: A comparative survey was carried
      out in a group of children with constipation and another group without
      constipation selected from a random sample. Data were collected from mothers
      using a structured questionnaire. Children with chronic constipation were
      expected to have undergone painful defecation or defecation with effort during at
      least thirty days with stools of hard consistency and/or bowel movements
      frequency below three times per week. RESULTS: An assessment was made of the
      variables: inappetence, abdominal distension, abdominal pain, fecal bleeding,
      soiling, urinary problems and vomit. Statistical differences were observed among
      children with and without constipation for inappetence, abdominal pain and faecal
      bleeding (p<0.05). CONCLUSIONS: An association was detected between the signs and
      symptoms analyzed and constipation. This study stresses the need to investigate
      accurately whether children have constipation and the extent of its relationship
      with those complications.

PMID- 14647674
TI  - [Role of anorectal manometry in the differential diagnosis of chronic
      constipation in children]
AB  - OBJECTIVES: 1. To evaluate the role of anorectal manometry in recognizing
      patients with histological abnormalities of the myenteric plexus as the cause of
      chronic constipation. 2. To correlate clinical features with the etiology of the
      constipation.METHODS: The etiology of the constipation was identified
      retrospectively from the medical records of 57 patients submitted to anorectal
      manometry. The test was performed in the Pediatric Gastroenterology Laboratory of
      the University Hospital of the State University of Campinas Medical School. The
      procedure was performed using a single-balloon system in which a water-perfused
      pressure transducer was interfaced with a polygraph and displayed on a computer
      screen. Manometry was performed in patients who, after 6 to 23 months of intense
      medical treatment using osmotic laxatives and dietary fibres (20 g/d), continued
      to develop fecal impaction and/or needed evacuatory enema. Regularization of
      bowel movements during at least 24 months follow-up or the visualization of
      abnormalities in myenteric plexus in rectal biopsy were used as reference points
      for the definitive diagnosis.RESULTS: Rectoanal reflex was present in 44 of the
      57 patients (77%). Thirteen patients with a negative reflex underwent rectal
      biopsy which showed abnormalities of the ganglion cells in 10. Subsequent
      manometry performed on those three patients revealed a normal rectoanal reflex.
      Sensitivity, specificity, positive and negative predictive values of the
      manometric test were 1.0, 0.94, 0.77 and 1.0, respectively.CONCLUSIONS: Anorectal
      manometry is a diagnostic technique with very small possibility of error in
      differential diagnosis between constipation of a chronic functional nature and
      that which is secondary to ganglion cell abnormalities.

PMID- 14647675
TI  - [Intra-cranial hemorrhage in infants due to vitamin K deficiency - report of 2
      cases]
AB  - OBJECTIVE: Drive attention to the late form of the hemorrhagic disease of the
      newborn, secondary to vitamin K deficiency, as a cause of intracranial hemorrhage
      in young infants.METHODS: The authors describe and analyze two cases of late
      hemorrhagic disease of the newborn, secondary to vitamin K deficiency, producing
      intracranially hemorrhage during the second month of age. The most important
      publications on this subject are reviewed.RESULTS: Both infants had not received
      prophylaxis with vitamin K at birth. They were both being fed exclusively on
      breast milk. They developed intracranial hemorrhage, and the clotting defect was
      rapidly corrected with intramuscular vitamin K. At 3 and 4 years of age, one of
      them has showed normal psychomotor development, and the other has showed moderate
      developmental delay with microcephaly.CONCLUSION: Late hemorrhagic disease of the
      newborn must be considered in young infants, between 2 and 12 weeks of age, with
      intracranial hemorrhage, especially those fed exclusively on breast milk who did
      not receive vitamin K at birth. It may produce neurodevelopmental delay. The
      clotting defect is rapidly corrected with intramuscular vitamin K. This condition
      is preventable. The prophylaxis is recommended with 1 mg of intramuscular vitamin
      K to all newborns, at birth, even without risk factors.

PMID- 14647676
TI  - [Coxsackie B2 virus fatal meningoencephalitis in a student]
AB  - OBJECTIVE: To present the case of a girl who was previously healthy but had fatal
      evolution due to Coxsackie B2 viral meningoencephalitis.METHODS: The authors
      describe the case of a female child with fatal meningoencephalitis caused by
      Coxsackie B2 virus and present a review of the literature (Medline and
      Lilacs).RESULTS: The girl was eight years old when she presented
      meningoencephalitis with bad evolution, leading to death on the 32nd day of
      internation. The exams showed positive serologic reaction to Coxsackie B2. The
      virus taken from two stool samples was isolated. The CRF exam showed an increase
      four times higher on Coxsackie B2 titulation.CONCLUSION: The death of healthy
      patients with enteroviral encephalitis, as described here, is rarely dealt with
      in the medical literature, perhaps because of lack of clinic suspicion. This case
      tries to drive attention to the importance of an early etiologic diagnosis in the
      meningoencephalities and the search for specific etiological treatment.

PMID- 14647677
TI  - [Calcifications from cardiac etiology in chest radiography]
AB  - OBJECTIVE: Children s chest X-ray calcification images can be related to
      pulmonary, mediastinal and rarely cardiac parenchymatous pathology. This report
      describes cases of cardio thoracic calcifications. We emphasize the importance of
      chest X-ray to track thoracic calcifications. In spite of the fact that it is
      rare, the cardiac etiology must be considered due to the possibility of surgical
      treatment.METHODS: Regarding the period from 1988 to 1997 the authors reviewed
      the chest X-rays of 2108 patients. In 3 of them thoracic calcifications of
      cardiac etiology were observed.RESULTS: Of these three patients, two were 7 years
      old and the third was 3 years old. Case 1 presented a calcification in the right
      atrium topography caused by a heart tumor of Fibroma type. In case 2 the
      calcification was in the pulmonary trunk, presenting as a calcified aneurysm of
      the ductus arteriosus. In case 3 the child had pulmonary stenosis and the chest X
      ray showed a calcified image on the left cardiac boards caused by a thrombo in
      the right ventricle wall.CONCLUSION: The authors emphasize the importance of
      chest X-ray in the diagnosis of thoracic calcifications, and comment that in
      spite of the being rare, the cardiac causes should be considered due to the
      possibility of surgical treatment.

PMID- 14647678
TI  - [Hypotonic infants and the Prader-Willi Syndrome]
AB  - OBJECTIVE: To describe 6 patients with less than 3 years of age that were
      diagnosed with Prader-Willi syndrome (PWS) due to hypotonia, poor sucking, slight
      facial anomalies and minor abnormalities of hands and feet. PWS is a
      neurobehavioural disorder characterized by two distinct phases; in the first, the
      neonate presents variable degree of hypotonia, feeding problems with none or poor
      sucking; hypogonadism, characteristic facial features with almond shaped eyes,
      narrow bifrontal diameter and down-turned corners of the mouth. Neuropsichymotor
      development is delayed. Hypotonia is non progressive and tends to improve between
      8 and 11 months of age. The second phase then starts and is characterized by
      increasing hyperphagia and obesity, among other features. Unfortunately, most PWS
      patients are diagnosed only after obesity is installed. METHODS: Methylation,
      microsatellites analysis and karyotypic studies by traditional and in situ
      hybridization techniques were done. RESULTS: A deletion of chromosome segment
      15q11q13 was disclosed in 4 and maternal disomy in two patients. CONCLUSION: The
      diagnosis of PWS is generally established after the onset of obesity. So, we
      suggest that the genetic analysis must be carried out in children with severe
      hypotonia of unknown cause, poor sucking and some facial features of PWS (small
      hands and feet, hypogonadism, hypopigmentation, almond eyes and narrow bifrontal
      diameter). This can allow the early diagnosis and avoid invasive exams necessary
      for neuromuscular disorder diagnosis like muscle biopsy and
      electroneuromiography, wich frequently are associated with inconclusives results.

PMID- 14647679
TI  - [Gene therapy for inherited metabolic disorders: a feasible alternative]

PMID- 14647680
TI  - [Tuberculin test in the diagnosis of childhood tuberculosis]

PMID- 14647681
TI  - [Gene transfer as treatment for metabolic inherited liver diseases]
AB  - OBJECTIVE: To study gene transfer looking for its future clinical application in
      the treatment of metabolic inherited liver diseases. METHODS: Bibliographic
      review about the subject. RESULTS AND CONCLUSIONS: Gene transfer into the liver
      would be an alternative to liver transplantation to treat some inherited
      metabolic diseases. Various vectors have been employed for gene transfer,
      including retrovirus vectors, whose integration into the chromosomal DNA would
      allow stable long term expression of the transgene. The integration of retrovirus
      vectors into the genoma of the target cell is only possible during mitosis.
      Therefore, these vectors must be delivered during hepatic regeneration induced by
      partial hepatectomy, for example. Another obstacle to be overcome is the extra
      hepatic dissemination of retrovirus, in particular to the germinals cells, due to
      the risk of changing the genetical heritage of the progeniture.

PMID- 14647682
TI  - [Antituberculosis chemoprophylaxis in children]
AB  - OBJECTIVE: To present a review of the indications of antituberculosis
      chemoprophylaxis in childhood, based on Brazilian official rules of the National
      Program for the Control of Tuberculosis of the Ministry of Health and the new
      tendencies pointed by the Brazilian Consensus on Tuberculosis. METHODS: Articles
      on the theme were selected from Medline and publications of the Ministry of
      Health. RESULTS: The chemoprophylaxis is an effective and safe form of prevention
      of tuberculosis in childhood. It does not conflict with the BCG vaccination
      program, because it aims at avoiding that tuberculosis infection develops into
      disease. CONCLUSIONS: International proposals an recent national tendencies
      recommend the expansion of chemoprophylaxis indications in childhood. Thus
      measures that expand its use in our country are needed.

PMID- 14647683
TI  - [Tuberculin test in the diagnosis of childhood tuberculosis: Analysis of
      quantitative and qualitative features]
AB  - OBJECTIVE: To evaluate the role of the tuberculin test in the diagnosis of
      tuberculosis in children. METHODS: Test diagnosis study; Tuberculin test with PPD
      Rt 23 (2 UT) was performed in 158 children, distributed in 2 groups: 101 no
      tuberculous, BCG vaccinated children and 57 tuberculous ones (diagnosis by
      clinical-radiological and epidemiological features). The interpretation of the
      tuberculin test was made by quantitative analysis (Mantoux test) and qualitative
      analysis (Koch and Listeria phenomena). RESULTS: Using cutoff = 10mm in Mantoux
      test, we found sensitivity of 85.9% and specificity of 86.1%. The qualitative
      analysis (Koch phenomenon), showed sensitivity of 77.2% and specificity of 98%.
      CONCLUSION: The qualitative analysis of the tuberculin test was useful in the
      diagnosis of tuberculosis in children, associated to the Mantoux test
      interpretation.

PMID- 14647684
TI  - [Energy balance in infants born from HIV seropositive mothers]
AB  - OBJECTIVES: A nutritional evaluation of infants born from HIV seropositive
      mothers was carried out during their follow up and diagnostic investigation. The
      energy balance (EB) of infected and noninfected children were compared. METHODS:
      The energy balance (intake energy, fecal energy, and resting energy expenditure)
      was prospectively determined by indirect calorimetry, considering 13 infants (6
      girls and 7 boys) between 1 and 6 months of age, born from HIV positive mothers.
      This was made in two opportunities: before and after the diagnosis of the
      disease. A full nutritional assessment, including clinical examination and
      anthropometric measures (weight, height and skinfold thickness), was also
      determined in these two opportunities. After the definite diagnosis, the infants
      were finally assembled in 2 different groups: infected (5 in 13) and noninfected
      (8 in 13). The children were monthly submitted to clinical evaluations and
      orientation, during all the study. RESULTS: By analyzing the anthropometric
      measures of the two groups, it was observed that the infected group had
      malnutritional manifestations since the first evaluation. The resting energy
      expenditure (kcal/kg/dia) of the infected group was higher than that of the
      noninfected group: 64.5-/+16.8 vs 48.0-/+5.7 (p<0.05) at the first evaluation and
      68.0-/+11.7 vs 51.8-/+3.1 (p<0.05) at the second, respectively. CONCLUSION: The
      higher resting energy expenditure of the children in the infected group might be
      the cause of the protein energy malnutrition during the asymptomatic phase when
      the diagnosis was uncertain.

PMID- 14647685
TI  - [Role of oxidative stress in the maintenance of inflamation in patients with
      juvenile rheumatoid arthritis]
AB  - OBJECTIVE: To determine the level of cellular oxidative stress blood markers and
      the enzymatic system of antioxidant defense establishing the oxidative profile in
      patients with Juvenile Rheumatoid Arthritis. METHODS: Case-control study that
      included 64 patients (46 of female sex) with Juvenile Rheumatoid Arthritis (JRA)
      following clinical control in the Pediatric Rheumatology Service of the Vall
      dacute;Hebron Hospital, Barcelona, Spain. The patients were separated in three
      subtypes based on the pattern of onset within the first six months of disease:
      polyarticular, pauciarticular and systemic. The control group included 60
      patients (38 of female sex) following clinical control to diseases of non
      inflammatory nature, in the same hospital. The plasmatic levels of
      malondialdehyde (MDA), lipoperoxide (LPO), hydroperoxide (HPX), carbonile groups
      (CG) of proteins and gluthathione and the enzymatic activities of Superoxide
      dismutase (SOD), gluthathione peroxidase (GSH-Px) and gluthathione reductase were
      determined. RESULTS: The group of patients with JRA presented high concentrations
      of lipid peroxidation products, evaluated by determining the plasmatic levels of
      MDA, LPO, and HPX; oxidative damage of the circulate protein, determined by CG
      contents of plasma proteins; elevation of enzymatic activity of SOD and GSH-Red;
      decrease of GSH-Px activity and GSH levels. CONCLUSIONS: Our results show the
      presence of molecular damage determined by oxygen free radicals in the JRA
      patients. The SOD activity and the changes of gluthathione redox enzymatic cycle
      confirm the decrease of capacity of cellular defense system against the induced
      toxicity of oxidative stress in these patients.

PMID- 14647686
TI  - [Mensurement of airflow resistance in neonatal prongs of nasal CPAP]
AB  - OBJECTIVE: To measure airflow resistance in prongs of nasal CPAP, making use of
      different gas admission flow (GAF) in the ventilation circuit, in different
      internal diameters of the nasal prongs, besides verifying whether a GAF
      responding only to the demand of three times the minute-volume(MV) is enough to
      the circuit not to be cause of CO(2) retention. METHODOLOGY: Nasal prongs,
      assembled in the original circuits, were used, having their prongs kept open to
      the atmosphere. Pressure was read at a pressure monitor, in water centimeters,
      connected to the appropriate entrance of the circuit. A flowmeter balanced to the
      pressure was used, gauged at 50 psi, installed to the oxygen net of the Hospital,
      connected to the assessing set of the CPAP circuit. Initially, making use of the
      8 l/min flow and keeping the exhaling set of the circuit closed, it was possible
      to eliminate the nasal prongs larger than two once the measured resistance was
      equal to zero. Having nasal parts number zero, 1 and 2 selected for this study,
      the system was then assembled as for the neonate: the inhaling set to the gas
      source and the exhaling set sunk into different depths in the water seal (2, 4, 6
      and 8 centimeters). At the level of patient analysis, in order to assess the
      CO(2) retention, a mechanical pulmonary ventilation device was used as gas source
      and a nasal CPAP circuit was assembled to the device in adequate places. GAF
      values and FiO(2) were determined in the commands of the mechanical ventilation
      device. The assessment of gas concentration in the ventilation circuit was made
      while assisting two newborns. Gas samples were obtained within the ventilation
      circuit in the system assessing set (samples A), and right after the distal prong
      to the gas entrance (samples B). To determine MV the Tidal Volume (considered
      10ml/kg) was multiplied by the respiratory frequency of the patient; GAF was
      three times MV. RESULTS: To a maximum GAF of 8 litres/min, only prongs sized
      zero, 1 and 2 showed resistance to the flow, measurable by the method used. There
      was an increase in resistance in proportion to the raise of GAF and
      proportionally opposite to the internal diameter of some prongs. Maximum
      difference in CO(2) partial pressure obtained from the gas given to the
      ventilation circuit and the one obtained from the nasal prongs was, in average,
      0.43mmHg (p <0.5). CONCLUSIONS: Taking into account that during ventilation
      assistance through nasal CPAP there is the possibility of GAF incurring in the
      increase in resistance, what would involve a greater effort from the newborn to
      overcome such resistance during exhaling into the system (generating possibly an
      unexpected CPAP), and minimum GAF determined is that sufficient to meet no more
      than three times the MV, the conclusion is that prongs with the largest internal
      diameter possible and GAF only the necessary to meet, at least, the needs of the
      demand three times the MV should be used during this therapeutic procedure.

PMID- 14647687
TI  - [Prevalence of breastfeeding in the city of Sao Carlos, Sao Paulo]
AB  - OBJECTIVE: To verify the prevalence of breastfeeding in the city of Sao Carlos.
      METHOD: For the collection and treatment of data regarding prevalence of
      breastfeeding we used the LACMAT 3.3 program. During Vacination National Day
      (1998, August 15) 3,326 persons responsible for children 2 years old or younger
      were interviewed. RESULTS: It was verified that 52.4% of the children under a
      month old were on exclusive breastfeeding. Out of 532 children under 4 months
      old, 73.3% were being breast fed: 37.8% exclusively breast fed and 17.3% under
      predominant breastfeeding. It was observed that 31.7% of the children under 4
      months received some other form of nourishment, such as fruit and mush, and on
      the fifth month, this percentage went to 62.3%. CONCLUSIONS: The results of this
      study demonstrated that the situation of breastfeeding in Sao Carlos is far from
      what the WHO recommends, this confirming the need to implement actions of
      promotion, protection, and support to breastfeeding in the health public services
      of the municipality.

PMID- 14647688
TI  - [Choledochal cyst: a 10-year experience]
AB  - BACKGROUND: Choledochal cyst is a rare abnormality usually found in infancy and
      childhood and mainly in females. Outcome depends on early diagnosis, complete
      resection of the cyst and proper hepaticoenterostomy.OBJECTIVE: The aim of this
      paper is to evaluate the outcome of 18 patients operated in ten years. METHODS:
      Retrospective chart review. RESULTS AND DISCUSSION: Age ranged between 20 days
      and 13 years (mean 3 years). Fifteen (83%) were female and 03 (17%) male. Signs
      presented included 15 (83%) with jaundice, 11 (61%) with dark urine, 10(55%) with
      pale colored stools, 09 (50%) with abdominal pain and palpable mass in only
      02(11%). Ultrasonography identified the cyst in 14 (77%) patients. Endoscopic
      retrograde cholangio-pancreatography demonstrated a long common duct in three of
      four cases. Anatomical types were: 09 type I, 01 type II, 07 type IV and 01 type
      V. Except for one patient who had a type V cyst, all patients underwent cyst
      resection plus Roux-en-Y hepaticojejunostomy. There were two (11%) early
      postoperative deaths related to deterioration of liver function. Thirteen (86%)
      of the 15 patients available to follow-up were symptom-free without late
      complications at a mean period of three years, and two (14%) patients developed
      chronic pancreatitis.

PMID- 14647689
TI  - [Idiopathic pulmonary hemosiderosis: case report]
AB  - OBJECTIVE: To alert pediatricians about the possibillity of childhood Idiopathic
      Pulmonary Hemosiderosis, in cases of anemia associated with chronic lung disease.
      METHODS: This article documents a case of Idiopathic Pulmonary Hemosiderosis in a
      6 year-old child, with histopathological documentation, and reviews it against
      published literature. RESULTS: A 6 year-old child with history of anemia and lung
      disease characterized by wheezing, recurrent pneumonia and digital clubbing was
      admitted to the hospital for investigation, where he suffered sudden respiratory
      failure and hemoptysis.He was submitted to a lung biopsy which showed a
      histopathological diagnosis compatible with pulmonary hemosiderosis. Therapy with
      high doses of corticosteroids was initiated with a good early response. After two
      and a half months of therapy he had a new bleeding episode, culminating in death.
      CONCLUSIONS: Idiopathic Pulmonary Hemosiderosis should be included as a possible
      diagnosis of children with anemia and chronic lung disease. This case is a good
      example.

PMID- 14647690
TI  - [Inhalation of nitric oxide - dependence: case report]
AB  - OBJECTIVE: Describe the hemodynamic response with rebound of pulmonary
      hypertension after withdrawal of inhaled nitric oxide (NO) in a pediatric patient
      with acute respiratory distress syndrome (ARDS). METHODS: Case report of a child
      with ARDS and pulmonary hypertension evaluated through ecocardiografic with
      dopller, receiving inhaled NO for a period of 21 days. RESULTS: There was a
      decrease of the pulmonary artery pressure (PAP) from 52 mmHg to 44 mmHg after the
      initial titulation of NO inhalation dose. After the withdrawal of inhaled NO an
      elevation of PAP was observed (55 mmHg). It was necessary to reinstall the
      inhaled NO to obtain a more appropriate value (34 mmHg). A new attempt of
      interruption of the inhaled NO after prolonged inhalation (20 days) resulted in a
      new clinic worsening and increase of PAP, with the indication to reinstall the
      inhaled NO. In the 24th day of permanence in the intensive care unit the patient
      died due to multiple organ dysfunction. CONCLUSIONS: The possibility of pulmonary
      hypertension rebound after withdrawal of inhaled NO is a complication that may
      have important clinical implications for patients who need a prolonged treatment
      with NO. This case report emphasizes these implications.

PMID- 14647691
TI  - [Asymptomatic cholelithiasis in an extreme premature child]
AB  - OBJECTIVE: To report a case of asymptomatic cholelithiasis in a premature young
      infant, presenting literature review. METHODS: The authors describe a case of
      asymptomatic cholelithiasis, incidentally diagnosed during a routine
      ultrasonographic exam, with spontaneous resolution. Literature review has been
      done from Medline and Lilacs, with quotations from articles of the last 45 years.
      RESULTS: Premature patient 28 weeks old with a cholelithiasis diagnosis at 5
      months, presenting the following risk factors: prematurity, total parenteral
      nutrition, prolonged use of Furosemide and sepsis. The patient remained
      asymptomatic until the spontaneous resolution occurred. CONCLUSION:
      Cholelithiasis in childhood has been reported in the literature as a rare
      condition, usually associated with Hemolytic disease. The widespread use of
      ultrasonography has contributed to an increase in the diagnosis of neonates and
      young infants in this condition. This case report highlights the idea of possible
      spontaneous resolution in cases of asymptomatic cholelithiasis incidentally
      diagnosed.

PMID- 14647692
TI  - [Persistent hyperinsulinemic hypoglycemia of infancy: case report]
AB  - OBJECTIVE: To report a case of Persistent Hyperinsulinemic Hypoglycemia in twins
      which is a situation not yet reported in the literature. METHODS: Report of
      seizures in identical twins, from consanguineous parents, with persistent
      hypoglycemia as cause of the seizures. Laboratory tests, performed for
      etiological investigation of the hypoglycemia, included thyroid hormones
      (T4/TSH), insulin, cortisol, growth hormone, stimulation test with glucagon (to
      evaluate the insulin/glucose relation), and histopathological study of the
      pancreas. RESULTS: Laboratorial investigation revealed a persistent hypoglycemia
      with hyperinsulinism which were confirmed with the stimulation test with
      glucagon. The histopathological exam showed a persistence of first generation
      pancreatic islet, confirming the diagnosis of Persistent Hyperinsulinemic
      Hypoglycemia in Infancy (the new denomination of Nesidioblastosis). CONCLUSION:
      Although rare, this condition must be early suspected early in the evaluation of
      hypoglycemia of the young infant, even out of the neonatal period, specially if
      the parents are consanguineous. The adequate therapy must be quickly initiated in
      order to prevent neurological damage.

PMID- 14647693
TI  - [Clinical use of helium-oxygen mixture revisited]

PMID- 14647694
TI  - [Organization of health practices and vulnerability to childhood diarrhea]

PMID- 14647696
TI  - [Primary ciliary dyskinesia in children]
AB  - OBJECTIVES: To point out primary ciliary dyskinesia as a cause of chronic
      respiratory disease in children.METHODS: A 10 year literature review on Medline
      and by direct research about the subject.RESULTS AND CONCLUSIONS: Primary ciliary
      dyskinesia is a disorder characterized by an abnormal mucociliary clearance. It
      affects both the upper and lower respiratory tracts and usually the clinical
      manifestations start in the first years of life. It can progress to
      bronchiectasis. Kartageners syndrome is the typical genetic manifestation. The
      diagnosis may be based on an abnormal saccharin test, but its confirmation
      depends on abnormal ultrastructure of the cilia or abnormal ciliary function.
      Many ciliary defects are currently known. The treatment is supportive, with
      measures to enhance mucociliary clearance, such as chest physiotherapy,
      prevention of infections by immunizations and prompt antibiotic therapy in the
      acute respiratory infections.

PMID- 14647695
TI  - [Global movement for health and against poverty: a call to all pediatricians and
      health professionals]

PMID- 14647697
TI  - [The use of helium-oxygen mixture in the ventilation study of children with
      chronic obstructive lung disease]
AB  - OBJECTIVE: To study the distribution of Tc-99m DTPA radioaerosol when heliox or
      oxygen are used in the nebulization of children and adolescents with chronic
      obstructive pulmonary disease during pulmonary ventilation scintigraphy. MATERIAL
      AND METHODS: Clinical randomized and controlled trial. Patients with chronic
      obstructive pulmonary disease (5 to 18 years old) who required pulmonary
      scintigraphy between March 1996 and September 1998 were included. Obstruction of
      the lower airway was measured by spirometry. Patients were randomized into two
      groups according to the gas used for nebulization during scintigraphy: heliox
      (80% helium and 20% oxygen) or oxygen. Scintigraphy studies were expressed as
      slope of the cumulative pulmonary radioactivity uptake curve and as the maximal
      cumulative radioactivity in the lung. The mean diameter of the Tc-99m DTPA
      particles generated by heliox and oxygen was measured by laser diffraction.
      RESULTS: Ten patients were allocated in each group. There were no statistical
      differences (P>0.05) in terms of gender, main diagnosis, signs of malnutrition,
      mean values of weight, height, body area, or spirometry results. The mean slope
      in the heliox group (5,039-/+1,652) was significantly different (P=0.018) from
      the mean slope of the oxygen group (3,410-/+1,100). The mean slope of patients
      with severe airflow obstruction in the heliox group was statically different
      (P=0.017) from the mean slope of patients with airflow obstruction in the oxygen
      group. In both groups, patients without evidence of airflow obstruction were
      similar in terms of mean slopes (P=0.507) and mean cumulative radiation in the
      lung (P=0.507). The mean diameter of heliox-generated Tc-99m DTPA particles was
      2.13 m (-/+0.62). This was statistically different (P=0.004) from the mean
      diameter of oxygen-generated particles (0.88-/+0.99 m). CONCLUSIONS: Nebulization
      with heliox was more efficacious than nebulization with oxygen for distribution
      and dispersion of Tc-99m DTPA radioaerosol in the lungs of children and
      adolescents with chronic obstructive pulmonary disease submitted to ventilation
      scintigraphy. The benefits of heliox over oxygen are more evident in the presence
      of lower airway obstruction. Without airway obstruction, we did not observe any
      difference in the distribution and dispersion of radioaerosol in the lungs.
      Although the mean diameter of the Tc-99m DTPA particles generated by heliox and
      oxygen was significantly different, the particles generated by both gases were
      still within the recommended range (between 1 and 5 m). Therefore, this
      difference does not account for the effects of heliox observed in this study.

PMID- 14647698
TI  - [Organization of health practices and vulnerability to childhood diarrhea]
AB  - OBJECTIVES: This study aimed to characterize, the organization of health
      practices related to the reduction of vulnerability to childhood diarrhoea.
      METHODS: A longitudinal study was carried out, with two interconnected
      transversal cuts, in 14 health services (11 health centres and 3 hospitals),
      located in six municipalities of Pernambuco that participated of the Diarrhoea
      Control Implementation Project coordinated by the Health State Department. The
      data collection was performed through observation, interviews with professionals
      and mothers of the children, and clinic histories revision. RESULTS: Overall,
      there was a high proportion of patients who either did not get consulted or had
      to wait for a long time after their arrival at the health service. No orientation
      was given on the use of oral rehydration salts at home; little advice on the
      signs and symptoms of an aggravating episode was given, an elevated number of
      drugs were prescribed to the children with diarrhoea; and there was high degree
      of omission to record the patients hydration status and the treatment offered.
      The educational practice is systematic only in 3 services, and only in these
      services there is delegation of activities to the nursing team and articulation
      with community health agents. On the 2nd phase of the study, one of the few
      changes identified was a discrete increase in weight measurement and its
      recording on a Chart. However, in the intervention period 69.6% of the health
      team members noticed an improvement on the pediatric assistance. CONCLUSIONS: The
      results reveal the great deficiency of the evaluated services in operating
      educational and healing activities related to diarrhoea control. So the observed
      practices concerning the attention to the children have contributed to increase
      childhood vulnerability, which shows the need to reorganize disease control
      actions, among the myriad of other actions related to this social group.

PMID- 14647699
TI  - [Diarrheal disease in hospitalized children - importance of the persistent
      diarrhea]
AB  - OBJECTIVE: In this paper we aim at analyzing the epidemiological and clinical
      patterns of children with age below 24 months who were hospitalized with
      diarrhoea in order to determine the prevalence of persistent diarrhoea (PD).
      PATIENTS AND METHODS: 300 children with diarrhoea were studied at the General
      Hospital of Pediatrics - IMIP in Recife, Northeast Brazil, considering the period
      from July 1993 to March 1994. It was a cross-sectional study. The socio
      demographic, clinical and evolutive characteristics of the sample were described.
      A bidimensional analysis was used to compare the groups with acute and persistent
      diarrhoea (PD) episodes. The proportion of deaths due to persistent diarrhoea was
      compared to the proportion of those due to acute diarrhoea. RESULTS: The majority
      of the children was younger than one year of age and come from low income
      families living in poor environmental and social conditions. At admission it was
      observed that the incidence of early weaning was high (44.2%); 71.1% of the
      children were below the third percentile for weight as compared with the NCHS
      curve. During the course of PD 33.2% of the children were hospitalized. Dysentery
      was detected in 52% of the cases. 106 children among the 246 observed (43.1%)
      recovered before the 14th day, while in 140 children (56.9%) diarrhoea persisted
      for two more weeks. PD contributed to extend the course of hospitalization and
      was associated with a higher proportion of fatal cases (72.9%). CONCLUSIONS: The
      majority of the children was younger than one year of age and come from low
      income families living in poor environmental and social conditions. PD frequency
      among the children who were hospitalized was high and accounted for a very high
      proportion of fatal cases. Inadequate management in the acute phase of diarrhoea
      was associated with the lengthening of the disease.

PMID- 14647700
TI  - [Recurrent pneumonia in a pediatric pulmonology outpatient unit: concept and
      prevalence]
AB  - OBJECTIVE: This study aimed to determine the prevalence of recurrent episodes of
      pneumonia in patients referred to the pulmonology outpatient unit at "Servico de
      Pneumologia Pediatrica" of the Instituto de Puericultura e Pediatria Martagao
      Gesteira/UFRJ and to review the recurrent concept in accordance to medical
      references currently available. METHODS: Data were obtained by reviewing all
      documented initial appointments from January 1st, 1995 up to April 30th, 1997.
      RESULTS: One hundred and one visits out of six hundred and thirty eight
      appointments with suspected diagnosis of recurrent episodes of pneumonia were
      studied. In less than 40% of this population the initial diagnosis was in
      accordance with the criteria usually required in our unit to perform such
      diagnosis. CONCLUSIONS: We concluded that the recurrent nature of pneumonia
      episodes should be further clarified and discussed with pediatricians because it
      is up to them to refer such patients to specialists. Furthermore we emphasize the
      importance of normal chest roentgenograms taken between acute episodes so that
      "recurrent pneumonia" can be adequately characterized. This may help identify
      those patients who need subsequent evaluation by specialists regarding
      complementary diagnosis.

PMID- 14647701
TI  - [Atypical arthritis in children with rheumatic fever]
AB  - OBJECTIVE: The aim of this study was to describe the clinical manifestations and
      to assess the occurrence of atypical arthritis in ARF patients attending a
      Pediatric Rheumatology Clinic at the University Hospital of Ribeirao Preto.
      METHODS: We have studied retrospectively the records of 120 attacks of ARF in 109
      children, 3-13 years old, who attended our clinic from January 1990 to December
      1995. All children fulfilled the Jones criteria. RESULTS: 77% of the attacks
      involved arthritis, 62% carditis, 32% chorea, 2.5% subcutaneous nodules and 1.3%
      erythema marginatum. The number of involved joints was 1 in 3 episodes of ARF, 2
      5 in 52, 6-10 in 30 and more than 10 in 5. Arthritis was considered atypical in
      43 (47%) of the 92 ARF episodes with arthritis, based on the following criteria:
      involvement of unusual joints (cervical spine in 24 children, hip in 15, small
      joints of the hand in 12 or feet in 13); monarthritis (3); duration longer than 3
      weeks (26); incomplete response to salicylates (18). Association of these
      atypical features were frequently present. For instance, considering the 24
      episodes with cervical spine involvement, the duration of arthritis was longer
      than 3 weeks in 13 cases, 10 had insufficient response to salicylates and the hip
      joint was also involved in 7. Time to reach diagnosis was longer than 4 weeks in
      59% of the patients presenting with atypical arthritis compared to 35% in the
      other patients (p=0.04). Different diagnosis were considered at the beginning of
      the disease in 40% of the 120 episodes and in 65% of the ones presenting with
      atypical arthritis (p=0.03). CONCLUSION: We conclude that atypical arthritis was
      present in a significant proportion of ARF episodes, adding an extra dilemma to
      the diagnosis of this intriguing disease.

PMID- 14647702
TI  - [Birth weight and maternal characteristics at the Maternity of Campinas along 25
      years]
AB  - OBJECTIVE: To study the secular trends of birthweight and maternal
      characteristics at the Maternity of Campinas, Sao Paulo, Brazil, from 1971 to
      1995. METHODS: The authors studied 18,262 newborns in the Maternity of Campinas.
      Birthweight and maternal characteristics were analyzed comparing changes occurred
      every 5 years. The data were analyzed by chi-square test, analysis of variance,
      multivariate logistic regression, and population attributable risk. RESULTS: The
      results showed a positive trend for birthweight only in the period between 1976
      and 1980 (P<0.05). The frequency of low birthweight was constant, remaining
      around 8.0%, but towards the end of the studied period, it started to be
      predominantly seen among preterm newborns. The frequency of favorable weight was
      below 70.0%. The authors observed an increase in the number of pregnant
      adolescents, pregnant women working outside home, unmarried mothers, cesarean
      sections, frequency of preterms, and decrease of parity (P<0.05). The maternal
      characteristics associated with low birthweight were: unmarried status, maternal
      age of 17 years old or less, maternal age of 35 years or more, public medical
      hospital assistance, nonwhite skin color, primiparity, multiparity, and female
      newborns. In the 90s, 44.3% of low birthweight was attributed to preterm
      newborns. CONCLUSIONS: Even with a positive development of the general conditions
      considered important to improve population s health, birthweight has not
      increased, probably as a reflex of other changes that held back this advance.

PMID- 14647703
TI  - [Breastfeeding in Montes Claros, Minas Gerais: a representative sample study]
AB  - OBJECTIVE: To evaluate the situation of breast-feeding in Montes Claros, among
      under-two-year-old children, and to determine variables associated to major risk
      for early weaning. METHODS: In this cross-sectional study interviews were carried
      out by trained personnel with 602 mothers selected randomly in the urban area of
      Montes Claros, from September to November, 1996. The survival analysis was the
      method used to calculate the prevalence and the median duration of breast
      feeding. The chi-square test was conducted to compare the proportions, and the
      level of significance was set at 5%. The prevalence ratio (PR) was used to
      measure the strength of the associations, with a 95% confidence interval. The
      logistic regression analysis was used to identify the risk factors for early
      weaning. RESULTS: The median duration of breast-feeding in general was 8.7
      months; however the median duration of exclusive breastfeeding was only 27 days.
      The risk factors for early weaning were low birth weight (OR=2.65; CI95%=1.10
      6.40), mothers with difficulties to breast-feed in the first days (OR=1.86;
      CI95%=1.21-2.85) and lack of posnatal medical incentive to breast-feed (OR=1.75;
      CI95%=1.15-2.66). CONCLUSIONS: For breast-feeding in general there is a better
      situation than that showed by other national reports, but it is still below
      recommended by WHO. There is a critical exclusive breastfeeding pattern. The
      factors related with early weaning denote a weak support of the maternal-infant
      health services to breast-feeding.

PMID- 14647704
TI  - [Helium-Oxigen (Heliox) mixture in airway obstruction]
AB  - OBJECTIVE: Demonstrate the effectiveness and the good outcome of the patients
      treated with helium-oxygen (Heliox) mixture. This mixture (Heliox) has been used
      in patients with airway obstruction, from different ethiologies, who did not
      respond to a conventional treatment with oxygen. METHODS: Case report of five
      patients that received Heliox as treatment for airway obstruction. All of them
      had good results without side effects during the treatment. CONCLUSION: Heliox is
      a promising treatment for severe airway obstruction with good results in a short
      period of time, until the final treatment is established.

PMID- 14647705
TI  - [Krabbe s disease - case report]
AB  - OBJECTIVE: Report a case of Krabbes disease with necropsy. METHODS: Review of
      medical and necropsy records. RESULTS: An 8 months-old male patient developed
      tremors, swallowing difficulty and excessive salivation for 4 months prior to
      admission, evolving with vomiting and fever. Physical examination showed
      microcephaly and diffuse pigmentation of the retinae. Neurological examination
      showed flexion of upper limbs with spastic hyperthony, symmetrical global
      hyperreflexia, nystagmus and spontaneous spasms. EEG showed multifocal irritative
      activity. There was increase in both CSF protein and gamaglobulin. The patient
      evolved with transitory hyperthermia, vomiting and pneumopathy, dying on the 23rd
      day after admission. Post mortem studies revealed microcephaly with widening of
      brain sulci. Histological examination revealed several globoid cells in the deep
      portion of the white matter, reactive gliosis and demyelination. CONCLUSIONS:
      These findings were similar to those in the world literature, indicating a poor
      prognosis due to substantial brain damage.

PMID- 14647706
TI  - [The Rapunzel syndrome - a case report: trichobezoar as a cause of intestinal
      perforation]
AB  - OBJECTIVE: To report a rare case of a patient with gastric trichobezoar extended
      through the small bowel, proper to the Rapunzel syndrome. CASE REPORT: Girl at
      age 7 with history and exams suggestive of peritonitis whose laparotomy
      demonstrated trichobezoar and jejunal perforation. She also presented alopecia
      and psychological disorder which were not totally eliminated despite the support
      given. CONCLUSION: A multidisciplinary view of the patient would have increased
      the suspicion rate for the pathology and would provide early diagnosis and
      treatment before complication was evident.

PMID- 14647707
TI  - [Hepatic hemangioma]
AB  - OBJECTIVE: To describe a case of a congenital hepatic hemangioma treated with
      surgery. METHODS: We report the case of a 6-day-old boy who presented a giant
      hepatic hemangioma, and describe its evolution. RESULTS: The child developed
      hemodynamic instability secondary to consumption coagulopathy and respiratory
      failure. The image studies were inconclusive. He was submitted to surgery with
      complete resection of the tumor. Pathology confirmed it was hemangioma. The child
      was discharged after 15 days and is well, without symptoms. CONCLUSIONS: Hepatic
      hemangiomas should be treated conservatively, with surgery reserved for
      intractable cardiac failure and/or refractory consumptive coagulopaty.

PMID- 14647708
TI  - [New treatments for critically ill children].

PMID- 14647709
TI  - [Rapid airway access].
AB  - OBJECTIVE: To review the steps involved in safe airway management in critically
      ill children. SOURCE OF DATA: Review of articles selected through Medline until
      April 2003 using the following key words: intubation, children, sedation. SUMMARY
      OF THE FINDINGS: Airway compromise is rare, but whenever it occurs, the situation
      depends on professionals trained to carry out safe, early, and rapid airway
      management, with no harm to the patient. The method currently advocated for
      airway management is rapid sequence intubation, which requires preparation,
      sedation and neuromuscular block. We observed that it is not possible to apply
      one single intubation protocol to all cases, since the selection of the most
      adequate procedure depends on indication and patient conditions. We defined the
      drug doses most commonly used in our setting, since little is know so far about
      the real effect of sedatives and analgesics. In most situations, the association
      of an opioid (fentanyl at 5-10 micro g/kg) with a sedative (midazolam at 0.5
      mg/kg) and a neuromuscular blocking agent are sufficient for tracheal intubation.
      CONCLUSIONS: Training, knowledge, and skill in airway management are of
      fundamental importance for pediatric intensive caregivers and are vital for the
      adequate treatment of critically ill children. We present an objective and
      dynamic text aimed at offering a theoretical basis for the generation of new
      protocols, to be implemented according to the strengths and difficulties of each
      service.

PMID- 14647710
TI  - [New therapies for intracranial hypertension].
AB  - OBJECTIVE: The main concepts involved in the therapeutic management of
      intracranial hypertension are revisited, including pathophysiology, monitoring,
      the traditional approach, and also the presentation of recently proposed
      therapies. SOURCE OF DATA: The main medical literature data bases (especially
      Medline and Lilacs) were searched for articles published in the last 10 years,
      and traditional text books and dissertations focusing the subject were consulted.
      SUMMARY OF THE FINDINGS: Intracranial hypertension may be associated with several
      cerebral neurologic lesions from traumatic, infectious or metabolic origin, and
      in severe cases may represent an important factor for morbidity and mortality.
      Increases in intracranial pressure interfere with cerebral blood flow; in order
      to maintain an adequate cerebral perfusion pressure, it is necessary to both
      reduce and control intracranial hypertension and combat low blood pressure from
      the very beginning of treatment. Adequate monitoring is essential, and the main
      points addressed in conventional management include elevation of the head of bed
      to 30 degrees C, central positioning of the head, optimization of hypocapnia,
      perfect metabolic and hydro-electrolyte balance, sedation, anti-convulsive
      therapy, liquor drainage, and the use of barbiturics, mannitol and furosemide.
      New therapies currently under investigation include the use of dexanabinol,
      hypertonic saline solutions, moderate hypothermia, decompressive craniectomy,
      optimization of cerebral perfusion pressure, and reduction in cerebral
      microvasculature pressure (Lund therapy). CONCLUSIONS: The use of new therapies
      to effectively control intracranial hypertension, especially in cases that are
      refractory to the usual treatment, represent a promising scenario in the
      management of this problem.

PMID- 14647711
TI  - [Management of the acute respiratory distress syndrome].
AB  - OBJECTIVE: To review the current support and treatment strategies of the acute
      respiratory distress syndrome. DATA SOURCES: Original data from our research
      laboratory and from representative scientific articles on acute respiratory
      distress syndrome and acute lung Injury searched through Medline. SUMMARY OF THE
      FINDINGS: Despite advances in the understanding of the pathogenesis of acute
      respiratory distress syndrome, this syndrome still results in significant
      morbidity and mortality. Mechanical ventilation, the main therapeutic modality
      for acute respiratory distress syndrome, is no longer considered simply a support
      modality, but a therapy capable of influencing the course of the disease. New
      ventilation strategies, such as high-frequency oscillatory ventilation appear to
      be promising. This text reviews the current knowledge of acute respiratory
      distress syndrome management, including conventional and non-conventional
      ventilation, the use of surfactant, nitric oxide, modulators of inflammation,
      extracorporeal membrane oxygenation and prone position. CONCLUSIONS: The last
      decade was marked by significant advances, such as the concept of protective
      ventilation for acute respiratory distress syndrome. The benefit of alternative
      strategies, such as high-frequency oscillatory ventilation, the use of surfactant
      and immunomodulators continue to be the target of study.

PMID- 14647712
TI  - [Noninvasive ventilation in pediatrics].
AB  - OBJECTIVE: To introduce the notion of noninvasive mechanical ventilation as an
      alternative for invasive ventilation in children, describing advantages and
      disadvantages, indications, and the process of equipment installation. SOURCE OF
      DATA: Literature review through PubMed/Medline, using as source articles focusing
      on noninvasive ventilation in pediatric populations, as well as consensus
      statements and metanalyses concerning noninvasive ventilation in adults. SUMMARY
      OF THE FINDINGS: The main indication for noninvasive ventilation is respiratory
      failure due to hypercapnia. It is contra-indicated in the presence of hemodynamic
      instability. The advantages of noninvasive ventilation include: the equipment is
      easy to install; it is not invasive and involves less discomfort; there is a
      lower incidence of complications associated with the endotracheal tube; lower
      cost. The disadvantages are: gastric distention; transient hypoxemia; facial skin
      necrosis. The equipment required for noninvasive ventilation includes an
      interface (mask) and a respirator. The removal of noninvasive ventilation
      equipment is relatively simple, but chronic patients may require assistance in
      the home. CONCLUSIONS: Noninvasive ventilation is a less costly, efficient and
      simple to perform alternative in cases of respiratory failure without hemodynamic
      instability.

PMID- 14647714
TI  - [Inhaled nitric oxide in pediatrics].
AB  - OBJECTIVE: To review the literature on inhaled nitric oxide and to describe its
      main clinical applications in pediatrics. SOURCE OF DATA: A 10 year literature
      review with selection of the most important publications on inhaled nitric oxide,
      using the Medline and Cochrane Systematic Review databases. SUMMARY OF THE
      FINDINGS: This review was organized as follows: introduction; metabolism and
      biological effects; clinical applications; dosage, gas administration and
      weaning; precautions and side-effects. Inhaled nitric oxide use was described in
      persistent pulmonary hypertension and hypoxia of the newborn, acute respiratory
      distress syndrome, primary pulmonary hypertension, heart surgery, chronic
      obstructive pulmonary disease, sickle cell anemia, and bronchospastic disease.
      CONCLUSIONS: Inhaled nitric oxide is a therapeutic approach with wide clinical
      applications in pediatrics. Its use is safe when administered in pediatric
      intensive care units under strict monitoring. As a pulmonary vasodilator, nitric
      oxide has beneficial effects on gas exchange and ventilation. Controlled trials,
      focusing on early gas administration should be performed under many clinical
      conditions, especially acute respiratory distress syndrome.

PMID- 14647713
TI  - [Adrenal insufficiency in children with septic shock].
AB  - OBJECTIVE: To review the criteria for diagnosing and treating adrenal
      insufficiency in patients with septic shock. SOURCE OF DATA: Articles published
      in Brazilian and foreign journals selected through these publications websites
      and Medline, as well as references cited in key articles. SUMMARY OF THE
      FINDINGS: The literature reports a range betwen 17 and 54% for the finding of
      adrenal insufficiency in patients with septic shock. There is no consensus for
      diagnosing adrenal insufficiency in patients suffering from critical diseases,
      particularly in patients with septic shock. The presence of volume-refractory and
      catecholamine-resistant septic shock suggests this condition, while basal
      cortisol under 25 micro g/dl is a diagnostic criterion indicating adrenal
      insufficiency. The adrenal stimulation test is a useful resource for identifying
      patients with relative adrenal insufficiency. Our testing option for adrenal
      stimulation in children is the use of corticotropin in low doses (0.5 micro
      g/1,73 m(2)). An increase of less than 9 micro g/dl in the value of
      postcorticotropin-stimulated cortisol suggests the presence of occult (relative)
      adrenal insufficiency. In patients with septic shock presenting adrenal
      insufficiency, either suspected or confirmed, the administration of
      hydrocortisone in shock or stress doses can be vital for a favorable clinical
      outcome. CONCLUSIONS: The existing data, although controversial, already provides
      a basis to determine when to begin hormone replacement therapy, the serum level
      of cortisol accepted as adequate, and the choice of corticotropin doses for
      performing the adrenal stimulation test and diagnosing occult or relative adrenal
      insufficiency in patients with septic shock.

PMID- 14647715
TI  - [Hypertonic solutions for pediatric patients].
AB  - OBJECTIVE: To describe the current knowledge and indications for use of
      hypertonic saline solutions in pediatrics patients. SOURCE OF DATA: Medline
      recent review articles and personal files. SUMMARY OF THE FINDINGS: Basic
      physiologic principles were reviewed concerning the distribution of fluid inside
      the intravascular, interstitial and intracellular compartments. We also reviewed
      the findings concerning the mechanisms responsible for the rapid onset of
      cardiocirculatory effects and the additional effect of the colloid component.
      Finally, we present the medical terms used in the context of small-volume
      resuscitation, the indications for clinical use, the evidence from clinical
      research (hemorrhagic shock, preclinical trauma care, septic shock, and head
      trauma), and the disadvantages and potential adverse effects of small-volume
      resuscitation. CONCLUSIONS: Resuscitation by means of hypertonic saline solutions
      associated or not with colloid solutions is one of the most innovative concepts
      for primary resuscitation from trauma and shock established in the past decade.
      Currently, the spectrum of potential indications involves not only prehospital
      trauma care, but also perioperative and intensive care therapy. However,
      additional randomized double-blind studies are required with both children and
      adult patients to confirm the advantages of the method in terms of survival.

PMID- 14647716
TI  - [Advances in sepsis diagnosis and treatment].
AB  - OBJECTIVE: To present a critical and updated review about sepsis, focusing
      especially on diagnosis and treatment. SOURCE OF DATA: Literature review of
      Medline, including review articles, clinical trials and original research.
      SUMMARY OF THE FINDINGS: The International Sepsis Definitions Conference
      amplified the list of possible clinical and laboratory signs of sepsis, which may
      allow for more efficacious suspicion and management. In terms of laboratory
      evaluation, in addition to the research for infectious agents, many inflammatory
      response markers, such as inflammatory cytokines and procalcitonin, have been
      identified. However, they lack sensitivity and specificity for safe diagnosis. In
      terms of treatment, early intervention to prevent hemodynamic disturbances is
      still essential for a positive outcome, together with the appropriate use of
      antimicrobials. The value of treatments to remove toxins and to increase the
      innate immune response has not yet been established. The use of isolated
      inflammatory response blockers, at any stage of sepsis, does not decrease
      mortality. The use of corticosteroid makes a comeback with encouraging results,
      even in patients without sepsis-related adrenal insufficiency. A large study on
      activated protein C (drotrecogin-alpha ) reports a 6% decrease in mortality in a
      selected sample, suggesting the possibility of a better prognosis for sepsis
      patients. CONCLUSIONS: In comparison to the advances of the past few years,
      little has been achieved in terms of decreasing sepsis-related mortality due to
      the complexity of the pathogen-host relationships. The individual regulation of
      host reactions did not have the expected effects. The benefits of some known
      strategies were confirmed. Other types of treatment, such as corticosteroids and
      activated protein C therapies, are emerging as promising alternatives. Research
      indicates that the combination of immune modulator therapies is probably the best
      choice to improve outcomes in sepsis.

PMID- 14647717
TI  - [Exogenous surfactant therapy in pediatrics].
AB  - OBJECTIVE: To review current knowledge about the use of exogenous surfactants in
      the treatment of different lung diseases causing acute respiratory failure in
      children. SOURCE OF DATA: This review is based on the author's experience and on
      recent data retrieved from ONIA, Mdconsult, Medline and the Cochrane Database
      Library. SUMMARY OF THE FINDINGS: In spite of the success of the use of exogenous
      surfactants in Respiratory Distress Syndrome (RDS) of the newborn, some questions
      remain unanswered, such as the optimal administration timing - either very early
      (prophylactic), based on gestational age or on quick tests of lung maturity, or
      later, when the clinical picture becomes unequivocal. In other severe diseases
      requiring ventilatory support, the use of surfactants is still controversial, and
      data in the literature are limited and conflicting. However, successful use in
      several other diseases has been reported. Recent studies have focused on
      surfactant inactivation by substances that can be found in the airways. New
      surfactants with the addition of substances to control inhibition, such as
      polyethyleneglycol, are being tested for diseases in which inactivation seems to
      be a significant factor. CONCLUSIONS: Therapy with exogenous surfactants, even as
      a treatment for RDS, has not been thoroughly investigated. Further studies should
      be conducted to improve surfactants - mainly their resistance to inhibition - and
      the treatment of diseases other than RDS.

PMID- 14647718
TI  - [Immediate post-operative care following cardiac surgery].
AB  - OBJECTIVE: To present a care routine for children submitted to heart surgery.
      SOURCE OF DATA: Literature review of Medscape, MD Consult and PubMed. Analysis of
      the suggested conducts adopted by various services from different countries and
      comparison with the care routine at the Pequeno Principe Children's Hospital
      (Curitiba, state of Parana), where approximately 8,000 heart surgeries were
      performed in children from 1977 to April 2003. SUMMARY OF THE FINDINGS: Our
      hospital is a reference center for Cardiology and Heart Surgery in the state of
      Parana and neighboring states. The improvement of conditions for diagnosis,
      training of the clinical and surgical teams, better equipped ICU with more modern
      monitoring, training of ICU personnel from all areas to handle the post-operative
      requirements of patients submitted to heart surgery, an adequate hospital
      structure with advanced care in all pediatric and paramedic specialties have
      resulted in marked improvement in relation to previous years in terms of the
      results of surgical interventions in children with congenital or acquired heart
      disease, especially newborns and young babies with complex heart problems.
      CONCLUSION: Children with heart diseases, especially complex conditions, should
      be receive care at reference centers that can provide global care before, during
      and after the surgery.

PMID- 14647719
TI  - [Analgesia and sedation in emergency situations and in the pediatric intensive
      care unit].
AB  - OBJECTIVE: To review the current strategies for use of sedatives and analgesics
      in emergency rooms and intensive care units. SOURCE OF DATA: Original data from
      our emergency rooms and intensive care units; Medline literature review focused
      on sedatives and analgesic drugs; textbooks. SUMMARY OF THE FINDINGS: Despite the
      advances in understanding pain in children, in many critical care units the
      misguided treatment of pain and anxiety still results in significant morbidity.
      Difficulties in communication, invasive procedures and the belief that children
      do not have sufficient neurologic development to process noxious sensations are
      still a challenge in intensive care units. CONCLUSIONS: The last decade was
      marked by significant advances in understanding pediatric pain. Treating
      intensive care unit-related pain and anxiety has clear benefits which may
      influence the course of disease.

PMID- 14647720
TI  - [Intensive care therapy for cancer patients].
AB  - OBJECTIVE: To review the most important aspects of the clinical presentation and
      treatment of children with cancer in intensive care units. SOURCE OF DATA:
      Medline (1970 to 2003); search terms: children, cancer, oncology, intensive care,
      complications. General and pediatric oncology textbooks. SUMMARY OF THE FINDINGS:
      Practically all organs may be affected by cancer or by its treatment. The main
      complications include infections, hematological problems and electrolyte/
      metabolic disturbances. Intensive care therapy is necessary to correct organic
      dysfunctions (cardiovascular, respiratory, renal, gastrointestinal, and
      neurologic). Nutritional and emotional support, as well as pain control are
      fundamental aspects for recovery in children. The intensivist should be alert to
      interrupt intensive care measures if required. CONCLUSIONS: Many studies show
      that the use of intensive care therapy in children with cancer is not futile,
      with a reduction in mortality and improvement in the quality of life of these
      children in the medium and long terms.

PMID- 14647722
TI  - [Shock treatment in pediatric patients: a challenge to be faced].

PMID- 14647721
TI  - [A "good" death in pediatric ICU: is it possible?].
AB  - OBJECTIVE: In the modern pediatric intensive care unit (PICU) physicians are
      often faced with the need to interrupt life-sustaining treatment (LST) and to
      allow children to die when no further treatment options are available.
      Consequently, the importance of palliative care has been increasing in this
      context. The goal of this review is to provide intensivists with guidelines to
      allow PICU patients to have a more dignified and humane death. SOURCE OF DATA:
      Medline was searched using relevant key-words, emphasizing the topic of death in
      the PICU. The principles of palliative care medicine were then applied to this
      context. SUMMARY OF THE FINDINGS: To ensure a dignified death for a child
      receiving palliative care in the PICU some important measures must be taken, such
      as: let the family participate in the decision-making process in an open and
      honest manner; allow family members to perform their religious rites and rituals;
      offer them moments of complete privacy; effectively manage pain and discomfort,
      especially at the time of removal of LST; and finally, let the family be present
      when LST is interrupted, if they so desire. CONCLUSIONS: A child's death
      following withdrawal of LST in the PICU can be humane and dignified if basic
      principles of palliative care are followed. This is especially important in an
      environment that is notorious for the use of complex technology and described by
      the general public as inhumane.

PMID- 14647723
TI  - [Etiologic profile of bacterial meningitis in children--a transient reality].

PMID- 14647724
TI  - [Tympanostomy tubes].

PMID- 14647725
TI  - [Clinical practice parameters for hemodynamic support of pediatric and neonatal
      patients in septic shock].
AB  - BACKGROUND: The Institute of Medicine has called for the development of clinical
      guidelines and practice parameters to develop "best practice" and potentially
      improve patient outcome. OBJECTIVE: To provide American College of Critical Care
      Medicine clinical guidelines for hemodynamic support of neonates and children
      with septic shock. SETTING: Individual members of the Society of Critical Care
      Medicine with special interest in neonatal and pediatric septic shock were
      identified from literature review and general solicitation at Society of Critical
      Care Medicine Educational and Scientific Symposia (1998-2001). METHODS: The
      Medline literature database was searched with the following age specific
      keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary
      hypertension, nitric oxide, and extracorporeal membrane oxygenation. More than 30
      experts graded literature and drafted specific recommendations by using a
      modified Delphi method. More than 30 more experts then reviewed the compiled
      recommendations. The task force chairman modified the document until <10% of
      experts disagreed with the recommendations. RESULTS: Only four randomized
      controlled trials in children with septic shock could be identified. None of
      these randomized trials led to a change in practice. Clinical practice has been
      based, for the most part, on physiologic experiments, case series, and cohort
      studies. Despite relatively low American College of Critical Care Medicine-graded
      evidence in the pediatric literature, outcomes in children have improved from 97%
      mortality in the 1960s to 60% in the 1980s and 9% mortality in 1999. U.S.
      hospital survival was three fold better in children compared with adults (9% vs.
      27% mortality) in 1999. Shock pathophysiology and response to therapies is age
      specific. For example, cardiac failure is a predominant cause of death in
      neonates and children, but vascular failure is a predominant cause of death in
      adults. Inotropes, vasodilators (children), inhaled nitric oxide (neonates), and
      extracorporeal membrane oxygenation can be more important contributors to
      survival in the pediatric populations, whereas vasopressors can be more important
      contributors to adult survival. CONCLUSION: American College of Critical Care
      Medicine adult guide lines for hemodynamic support of septic shock have little
      application to the management of pediatric or neonatal septic shock. Studies are
      required to determine whether American College of Critical Care Medicine
      guidelines for hemodynamic support of pediatric and neonatal septic shock will be
      implemented and associated with improved outcome.

PMID- 14647726
TI  - [Etiological profile of bacterial meningitis in children].
AB  - OBJECTIVE: To determine the etiologic profile and analyze some epidemiological
      aspects of children with bacterial meningitis admitted to a public teaching
      hospital. METHODS: A prospective study was conducted on children with clinical
      and laboratory diagnosis of bacterial meningitis, admitted to Hospital das
      Clinicas da Universidade Federal de Uberlandia, from January 1987 to January
      2001. Patients with meningitis associated with trauma, intracranial devices or
      malformations of the neural tube, and tuberculosis, were not included in the
      study. RESULTS: From a total of 415 children with bacterial meningitis, the
      etiologic agent was detected in 315 (75.9%): Haemophilus influenzae b in 54.2%,
      meningococci in 20.6%, pneumococci in 18.1% and other agents, in 6.9%. Previous
      antibiotic treatment, observed in 47.2% of the cases, led to a significant
      decrease in positive blood cultures (from 50.8% to 38.7%) and in cerebrospinal
      fluid cultures (from 71.7% to 57.6%). Among children younger than 48 months
      Haemophilus influenzae b was predominant, particularly when compared to
      meningococci. The overall mortality was 10.1%, with a significant difference
      between the rates of pneumococcal (17.5%) and meningococcal meningitis (4.6%).
      CONCLUSIONS: Children affected by Haemophilus influenzae b and by pneumococci
      were younger than those with meningitis caused by meningococci. The blood and/or
      cerebrospinal fluid culture remains an important laboratory tool for etiologic
      diagnosis, despite the negative impact caused by antibiotic previous treatment.
      The agents most commonly detected were Haemophilus influenzae b, meningococci and
      pneumococci. Bacterial meningitis continues to present an important mortality
      among children, particularly when caused by pneumococci.

PMID- 14647727
TI  - [Tympanostomy tubes and water].
AB  - OBJECTIVE: An in vitro study was conducted to set the necessary pressure in
      fluids that could break resistance and cross the opening of a tympanostomy tube.
      METHODS: A water column model was created and graduated in centimeters from base
      to top. We adapted three sorts of tympanostomy tubes. In each model, fluids were
      tested (tap water, seawater, river water, soapy water and eardrops). The column
      was filled with fluid until a threshold was reached, flowing through the tube
      opening. The threshold was registered and represented the pressure in cmH2O.
      RESULTS: The results show that pressure is necessary so that a fluid can cross
      the opening of a ventilation tube. CONCLUSION: In spite of limitations of our in
      vitro study, the literature suggests that no ear protection is needed during
      shower, since there is neither direct flow of water nor pressure in the ear.
      Bathing with soapy water is potentially dangerous due to the reduction in surface
      tension. The direct relation of pressure and surface tension through the opening
      of tympanostomy tubes indicates the need to decrease pressure when diving and to
      avoid strong head movements in the water.

PMID- 14647728
TI  - [Musculoskeletal manifestations as the onset of acute leukemias in childhood].
AB  - OBJECTIVE: To study the frequency, the clinical features and laboratory exams of
      patients with musculoskeletal symptoms at the onset of acute leukemia. METHODS:
      Retrospective, descriptive study including patients diagnosed with acute
      leukemia, and treated at the Institute of Pediatric Oncology of UNIFESP, carried
      out from November 1999 to February 2000. The data on musculoskeletal complaints
      were obtained from a questionnaire. The medical records were revised in order to
      get data on the clinical examination and laboratory tests at the beginning of the
      illness. RESULTS: Sixty-one children were included in this trial, 93% with acute
      lymphoid leukemia, and 7% with acute myeloid leukemia. Thirty-eight patients
      (62%) had musculoskeletal pain at the onset. Arthritis was observed in eight
      patients. The mean number of involved joints was 2.5 (1-6). The most frequently
      involved joints were the knees, ankles and elbows. Three patients (4.9%) had
      normal blood count. Low hemoglobin was reported in 54 patients (88%) (in six
      patients it was the only hematological abnormality), leukopenia in 14 (22%),
      leukocytosis in 26 (42%) and low platelet count in 46 (75%). CONCLUSIONS: The
      musculoskeletal symptoms are common at the onset of acute leukemia so, malignancy
      should always be ruled out in patients presenting chronic or acute arthritis or
      benign limb pain. The laboratory tests may be normal at the onset of the illness,
      making differential diagnosis more difficult.

PMID- 14647730
TI  - [Evolution of nutritional status in hospitalized children].
AB  - OBJECTIVE: To assess the evolution of nutritional status in children admitted to
      the Teaching Hospital of Universidade Federal de Alagoas. METHODS: A
      retrospective study was performed on 52 children (0-10 yrs) whose length of
      hospital stay exceeded 10 days (from February to July/2001). We compared their
      nutritional status, expressed in terms of Z score of the weight-for-age ratio at
      the beginning (T1) and at the end of the hospitalization period (T2). RESULTS:
      The predominant age range (44.2%) was less than 1 year (median=1.4 yrs). The
      hospitalization period varied from 10 to 77 days (median=20 days). Although the
      prevalence rates of protein-energy malnutrition (PEM) in T1 and T2 were,
      respectively, 71.2% and 69.2%, only 15.4% had this diagnosis on the medical
      records. These children diagnosed with protein-energy malnutrition presented
      extreme wasting and greater length of hospital stay than the others (PEM, n=8: 
      4.38 +/- 2.1, T=30 +/- 4.5; undiagnosed PEM, n=13: -3.13 +/- 0.9, T=23 +/- 18;
      other conditions, n=31: -0.63 +/- 1.1, T=21 +/- 13). Among the 52 children
      analyzed, only 29 showed positive weight variation. However, the average
      magnitude of negative Z values was higher than that of positive values: -0.56 and
      0.50. Children who remained in hospital for a longer period of time showed larger
      weight deficits, indicating that hospitalization did not contribute towards the
      improvement of their initial nutritional status. CONCLUSION: The prevalence of
      weight-for-age deficit among children at hospital admission was very high. This
      situation remained unchanged at hospital discharge.

PMID- 14647729
TI  - [Nosocomial infection and multiple causes of death].
AB  - OBJECTIVE: The purpose of this study was to evaluate the possibility for
      collecting data on nosocomial infections by means of death certificates. METHODS:
      The medical charts of children who died after 48 hours of their admission to a
      pediatric hospital were revised to get information about the causes of death.
      Death certificates were also revised to verify whether they were properly filled
      out. The death certificates were redrafted according to the data obtained from
      patients' medical charts. Nosocomial infections and procedures related to them
      were codified using the Supplementary External Causes of Injury and Poisoning
      codes of the International Disease Classification-9th Revision. RESULTS: The
      causes mentioned on medical death certificates compared with revised causes
      obtained after revision of patients' charts showed an agreement of 69.9%, with a
      Kappa coefficient of 0.65. Only one case of nosocomial infection was found on
      original death certificates, whereas the redrafted certificates revealed 88.9% of
      nosocomial infections in the study population up to fifteen days before death.
      CONCLUSION: Death certificates are not a good source of information on nosocomial
      infection because they are often filled out inadequately. The solution to this is
      to qualify physicians so that they can identify and record nosocomial infections
      on the patient's medical chart and complete death certificates accordingly.

PMID- 14647731
TI  - [Prevalence of chronic constipation in children at a primary health care unit].
AB  - OBJECTIVE: To study the frequency of chronic constipation in childhood at a
      Primary Health Care Unit and to observe its characteristics in this population.
      METHODS: The sample consisted of 313 children aged between one and 10 years
      treated at the Centro de Saude Escola, in the district of Tiberio, in the town of
      Ribeirao Preto. Among these, 84 children with chronic constipation were selected.
      The chi-squared test was used to compare the groups of constipated and
      nonconstipated children (p=0.01). RESULTS: The prevalence of chronic constipation
      was 26.8%. In the group of chronic constipation, 85.7% of the children had
      hardened stools, 25% showed reduction in fecal mass, 17.9% had an interval
      between evacuations longer than 2 days (constipated children), 14.3% revealed
      fecal soiling and 21.4% presented blood in stools. CONCLUSION: The prevalence of
      chronic constipation was high and the interval between evacuations was as an
      important diagnostic criterion for the selection of constipated children.

PMID- 14647732
TI  - [Prevalence of hepatitis A antibody in children and adolescents with chronic
      liver disease].
AB  - OBJECTIVE: To evaluate the prevalence of Hepatitis A virus (HAV) in children and
      adolescents with chronic liver disease in a unit of pediatric hepatology.
      METHODS: Between May 1999 and February 2001, we studied the prevalence of anti
      HAV in 60 children and adolescents with chronic liver disease, aged between 1 and
      16 years, from the Unit of Pediatric Hepatology of the Hospital de Clinicas de
      Porto Alegre. The total anti-HAV was determined by a commercially available
      competitive ELISA method (Abbott), and compared with age, sex, race, etiologic
      diagnosis and family income of each patient. RESULTS: A one-year old child was
      not included in the study because she presented twice with undetermined anti-HAV
      results. Among the other 59 patients, 14 (24%) presented a positive result of
      total anti-HAV. The ages of test-positive subjects varied between 1 and 16 years
      old (mean=7.7 years, median=8.5). The differences between positive and negative
      groups in relation to age, sex and race were not statistically significant.
      Family income was lower in anti-HAV positive patients, but this difference was
      not significant. The differences between the etiologies of liver diseases were
      probably more related to the age than to the etiologies of the diseases.
      CONCLUSIONS: In the studied population, the majority (76%) of children and
      adolescents with chronic liver disease are susceptible to hepatitis A virus
      infection and, consequently, they could present a more severe disease or even
      fulminant hepatitis A. We strongly suggest that these subjects receive Hepatitis
      A inactivated vaccine.

PMID- 14647733
TI  - [Infant death surveillance as an indicator of health care system effectiveness--a
      study conducted in northeastern Brazil].
AB  - OBJECTIVE: To evaluate the access to and quality of health care administered to
      infants based on postmortem data. METHODS: A descriptive cross-sectional census
      based study was carried out to assess the infant deaths that occurred in the town
      of Bom Conselho, state of Pernambuco, between January 1st 1999 and December 31st
      1999. Home interviews and inspection of medical records were used for data
      collection. Deaths were identified by consulting the Mortality Information
      System, health centers, public notary services, cemeteries, health workers, and
      midwives. RESULTS: Seventy-one of 72 deaths were investigated, with a loss of
      1.4%. The majority (69.4%) of deaths occurred in the postneonatal period and
      67.6% of them occurred at home. In 77.5% of the cases medical help was sought at
      least once, most frequently at emergency units (65.1%). However, 22.5% of the
      patients were not taken to any kind of health care service. Most health care
      services (90.9%) were less than one hour away from the patient's home, 78.5% were
      located in the town of residence and 97% of the consultations were carried out by
      doctors. Of 88 consultations, 39.8% resulted in hospitalization and 27.3% in
      discharge without arrangement of a follow-up appointment. In 84% of the cases the
      medication was provided free of charge. CONCLUSIONS: Death surveillance revealed
      restricted access to medical care and poor quality of health care administered to
      infants living in the referred town. The high rate of home deaths is related to
      access, whilst the journeys made by some of the mothers to health care units,
      during the illness that caused the death of their infants, points to the
      precarious organization of those services.

PMID- 14647734
TI  - [Clinical and nutritional aspects of Gaucher disease: prospective study of 13
      children at a single center].
AB  - OBJECTIVE: Gaucher disease is an autosomal recessive lysosomal storage disease,
      caused by mutation to the GBA gene (glucocerebrosidase gene) located on
      chromosome 1. The objective of the present study was to identify the clinical,
      nutritional, biochemical and genetic features of the patients with Gaucher
      disease treated at the Unit of Pediatric Hematology (Hospital das Clinicas
      Universidade Federal de Minas Gerais). METHODS: Thirteen patients were
      prospectively followed up. Gaucher disease was confirmed in all patients through
      the use of an enzyme assay test to measure glucocerebrosidase enzyme activity.
      Demographic and nutritional data, and biochemical findings obtained on admission,
      were studied. Genetic testing was performed in seven patients. The median age of
      follow-up was 5.3 years. Z scores for weight and height on admission and at the
      end of observation period were calculated. The standardized prevalence for
      malnutrition was calculated using the Mora method. RESULTS: The mean age at
      diagnosis was 5.8 years. The predominant clinical manifestations at diagnosis
      were hepatomegaly and splenomegaly, and all patients were classified as clinical
      type 1. Low platelet count and anemia were detected at diagnosis in eight and six
      children, respectively. The most frequent genetic mutation was N370S. One child
      died during follow-up due to septicemia, after splenectomy. The prevalence of
      malnutrition was 26% at admission and 48% at the end of the observation period.
      CONCLUSION: The analysis of data demonstrates that N370S and clinical type 1
      predominate in our Unit, characterizing the milder form of the disease. The
      irregular enzyme replacement therapy during the study period did not allow valid
      clinical conclusions on its efficacy.

PMID- 14647735
TI  - [Bone mineral density in children. Association with musculoskeletal pain and/or
      joint hypermobility].
AB  - OBJECTIVE: Joint hypermobility can be associated with benign musculoskeletal
      pain. The relation between hypermobility and low bone mineral density is still
      unknown. Osteoporosis can be observed in some genetic syndromes associated with
      joint hypermobility. The aim of our study was to detect the possible relation
      between joint hypermobility, benign musculoskeletal pain and bone mineral density
      in children. PATIENTS AND METHODS: Ninety-three children from 5 to 10 years of
      age were evaluated concerning the presence of joint hypermobility and the
      presence of musculoskeletal pain based on a questionnaire directed to parents. We
      also performed densitometry to measure bone mineral density. All children
      underwent an L2-L4 lumbar bone densitometry. RESULTS: Children were distributed
      into four groups according to the presence or not of joint hypermobility
      associated or not with musculoskeletal pain: 29 (31.2%) with hypermobility and
      pain, 20 (21.5%) with hypermobility and without pain, 22 (23.6%) without
      hypermobility and with pain and 22 (23.6%) without hypermobility and without pain
      (control group). Twenty-four children (25.8%) presented reduction in bone mineral
      density over 10% related to the adequate bone mineral density for age and gender.
      Bone mineral density was significantly lower in relation to the controls in the
      following groups: with hypermobility (independently of the presence of pain),
      with pain (independently of the presence of hypermobility), with hypermobility
      and without pain and without hypermobility and with pain. CONCLUSION: Bone
      mineral density may be lower in children with joint hypermobility (independently
      of musculoskeletal pain) and in children with pain (independently of
      hypermobility) when compared to controls.

PMID- 14647737
TI  - [Extracorporeal shock wave lithotripsy in the treatment of children's renal
      calculi].

PMID- 14647736
TI  - [Report of a Brazilian patient with Wolfram Syndrome].
AB  - OBJECTIVE: To report a case of a patient diagnosed with Wolfram Syndrome and
      brachydactyly type E. Wolfram Syndrome is characterized by the presence of
      diabetes mellitus, diabetes insipidus, atrophy of the optic nerve, alterations of
      the urinary tract, deafness and neurologic and psychiatric disorders. However,
      not all manifestations are present at diagnosis, indicating the necessity of long
      term follow-up of these patients. This long-term follow-up should be extended to
      the patients' closest relatives, having in mind the increased risk of occurrence
      of psychiatric disorders and diabetes mellitus among the heterozygous carriers of
      Wolfram Syndrome. DESCRIPTION: Male, white patients, only child of non
      consanguineous parents, was healthy until four years of age, when he presented
      with polydipsia and polyuria, being diagnosed with diabetes mellitus type I.
      Since then, he has needed regular insulin use, but has followed an inadequate
      diet due to socioeconomic problems. He was evaluated by the genetic service when
      he was 11 years old. Brachydactyly was observed on physical examination. In the
      course of the complementary investigation, bilateral atrophy of the optic nerve
      was observed; the visual evoked potential and the electroretinogram were
      compatible with extensive optic nerve injury. Both retinas were normal. The
      presence of insulin-dependent diabetes mellitus together with atrophy of the
      optic nerve is a sufficient criterion for the diagnosis of Wolfram Syndrome. The
      molecular investigation confirmed the diagnosis of Wolfram Syndrome. COMMENTS:
      The aim of the present report is to alert physicians about the association
      between diabetes mellitus and monogenic syndromes, such as Wolfram Syndrome.

PMID- 14647738
TI  - [Cranial sonographic uncommon findings in the neonatal period: clinical
      importance].

PMID- 14647739
TI  - [The meaning of nutritional status assessment].

PMID- 14647740
TI  - [Depression in childhood and adolescence: clinical features].
AB  - OBJECTIVE: This study reviews clinical features, evolution, comorbidity and
      suicidal behavior in childhood and adolescence depression. Its objective is to
      provide clear information on this common, severe and not very easily recognized
      pathology. SOURCES: Literature searches were performed through Medline (1991
      2000), with secondary-source follow-up. SUMMARY OF THE FINDINGS: Scientific
      concern about depression in childhood and adolescence is recent and up to the 70s
      depression was considered rare or nonexistent in this period. Current diagnostic
      systems define as basic features of depression in children and adolescents are
      the same ones found in adults for major depression episodes; however, researches
      emphasize the significance of the developmental process in the clinical
      manifestations, with predominant features in each phase. CONCLUSIONS: Nowadays,
      major depression in children and adolescents is understood to be a common,
      disabling and recurrent disease, with a high level of morbidity and mortality. It
      is an important public health problem.

PMID- 14647741
TI  - [Extracorporeal lithotripsy for the treatment of urolithiasis in children].
AB  - OBJECTIVE: Urinary lithiasis affects between five and 10% of the human population
      during their lifetime, only 2-3% of whom are children. Therapy of urolithiasis in
      the pediatric age group with minimally invasive methodology represents an
      attractive alternative. This study presents results of extracorporeal shockwave
      lithotripsy, a minimally invasive methodology, for the treatment of urinary
      lithiasis in children. METHODS: In the period between September 1991 and
      September 2000, 87 children were submitted to extracorporeal shockwave
      lithotripsy; as six of them presented with two calculi 93 urinary calculi were
      treated over that period. The Dornier-Philips lithotriptor was used in the
      procedures. RESULTS: Pelvic, superior and medium caliceal calculi were fragmented
      and eliminated in 87.7% and 77.8% of cases, respectively. Inferior caliceal
      stones were eliminated in 64.7% of cases. Only one of the three patients with
      staghorn calculi became stone-free after therapy (33.3%). All patients with
      ureteral calculi were stone-free after therapy. Bladder stones were fragmented
      and eliminated in 60% of cases. CONCLUSIONS: Extracorporeal shockwave lithotripsy
      is a safe and effective treatment for pelvic, caliceal, ureteral and bladder
      urolithiasis in children. Staghorn calculi have not shown satisfactory results
      when treated by this method. Extracorporeal shockwave lithotripsy results were
      influenced in our experience by the position and size of the treated calculi.

PMID- 14647742
TI  - [Hyperechogenicity of thalamic vessels in preterm newborn infants].
AB  - OBJECTIVE: The aim of this study is to evaluate possible pathologies associated
      with hyperechogenicity of thalamic vessels (HETV), which are found on brain
      ultrasounds (BUS), as well as to observe the frequency of their occurrence.
      METHODS: The sample was composed of 206 preterm newborn infants at Hospital de
      Clinicas de Porto Alegre (HCPA) from July 1998 to May 1999. All of them were
      submitted to BUS in the first week of life. Preterm children who needed hospital
      admission and had a term of informed consent signed up by their guardians were
      included in this study. Preterm newborn children with BUS showing intracranial
      hemorrhage and/or associated congenital malformation were excluded from this
      study. RESULTS: Through BUS it was possible to identify 65 preterm newborn
      children with HETV and 141 preterm newborn children without HETV. CONCLUSIONS: We
      identified the following risk factors for HETV: pelvic presentation, longer
      gestational period, increased birthweight and big for gestational age
      classification. On the other hand, mothers hypertension during the gestational
      period tended to protect infants from HETV. The newborn infants that presented
      convulsive crises during hospitalization had a 3.2-fold higher risk of having
      HETV when compared to the ones who did not go through any convulsive crises.

PMID- 14647743
TI  - [Diagnosis of subependymal cysts by brain ultrasound].
AB  - OBJECTIVE: The aim of this study was to describe the clinical data and
      sonographic evolution of subependymal cysts (SEC) and to compare alone SEC versus
      SEC combined with other brain abnormalities. METHODS: The diagnosis of SEC relied
      on the discovery of one/several cysts at the outer angle of one/both lateral
      ventricles detected by routine brain ultrasound tests in the first days of life.
      During the 1981-2000 period, 66 neonates had evidence of SEC in Port-Royal
      Department of Neonatal Medicine. The cases were divided into two groups: G-I,
      alone SEC; G-II, SEC combined with other brain abnormalities. Hospital charts
      were reviewed for gestational and delivery data and ultrasound scans were
      analyzed according to a preset list of items (dates, measurements, other
      findings). RESULTS: Patients with alone SEC had a higher gestational and
      birthweight, better birth conditions, and less respiratory morbidity. High rates
      of associated congenital anomalies were observed in both groups (19% in G-I, 13%
      in G-II, NS). Rare pre/perinatal infections did not show any association with
      SEC. SEC were uni or bilateral, single or multiple (string), with no difference
      between G-I and G-II. Unilateral SEC predominated in the left side (26/28,
      P<0.01). Serial examinations were carried out in 49/66 (74%), showing an increase
      in size of SEC in 21/49 (45%) in the first month of life, while 12 SEC (24%)
      disappeared. The 11 deaths occurred in neonates with other severe brain injuries
      (five peri-intraventricular hemorrhages, four periventricular leukomalacias)
      except one (diaphragmatic hernia). CONCLUSIONS: Alone SEC and SEC combined with
      other brain abnormalities follow the same morphologic pattern and evolution. The
      striking predominance in the left side may suggest another etiology. Both are in
      favor of a developmental deviation and not a viral fetopathy.

PMID- 14647744
TI  - [Evaluation of the nutritional status of Indian children from Alto Xingu,
      Brazil].
AB  - OBJECTIVE: To evaluate the nutritional status and estimate body composition of
      Indian children from Xingu Indigenous Park (XIP), rain forest Amazon region, by
      using anthropometry and bioelectrical impedance (BI) tests. METHODS: One hundred
      and sixty-four Indian children (89 girls and 75 boys) of unknown age were
      evaluated by means of anthropometry and bioelectrical impedance. Weight and
      height were used to calculate z-score for weight-for-height (W/H) index. Two
      equations based on the resistance values obtained from the bioelectrical
      impedance were used to determine body composition. The values obtained were
      compared to standard reference. RESULTS: Z-score median for weigh-for-height
      index was 0.59 (boys) and 0.46 (girls) (P=0.27), respectively. Among the children
      studied only 1.8% showed z-score W/H <-2 standard deviations (SD), and 3% showed
      z-score W/H >2 SD. Mean resistance values were 625.4 +/- 79.2 Ohms (girls) and
      588.8 +/- 68.9 Ohms (boys) (P<0.01). The percentage of body composition values
      obtained for girls were 14.2% fat mass (FM) and 85.8% fat-free mass (FFM), and
      11.7% (FM) and 88.3% (FFM). The values for the boys were 14.9% (FM) and 85.1%
      (FFM), and 10.3% (FM) and 89.7% (FFM). CONCLUSIONS: There were low rates of
      obesity and malnutrition, what leads us to believe that the nutritional status
      among the Indian children from XIP has been kept in good standard along the last
      three decades, even under some degree of the Western culture influence. The
      Indians' body composition enhanced the good nutritional status among the studied
      population. BI played an important role in the estimation of body composition in
      this field study.

PMID- 14647745
TI  - [Diagnostic screening of liver disease in cystic fibrosis].
AB  - OBJECTIVE: To determine the prevalence of clinical and biochemical abnormalities
      suggestive of liver disease in the population of patients with cystic fibrosis
      (CF) seen at the CF Outpatient Clinic of the Federal University of Minas Gerais;
      to describe the group of patients with liver disease and to compare it with the
      group without liver disease, regarding several clinical and laboratory variables.
      METHODS: Descriptive study, resultant of a prospective, and partially
      retrospective assessment of 106 patients with CF. Liver disease was defined by
      the presence of firm hepatomegaly (>2.5 cm from the right costal margin), and/or
      splenomegaly, and/or persistent and significant increase (>1.5 times the upper
      limit of normality, over six months) of at least two serum liver enzymes (alanine
      aminotransferase--ALT, aspartate aminotransferase--AST, alkaline phosphatase-
      ALP, gamma-glutamyl transpeptidase--GGT). RESULTS: Hepatomegaly was verified in
      seven patients (6.6%) and splenomegaly in five (4.7%). AST activity was altered
      in 18.9% of the patients, ALT in 9.4%, GGT in 11.3%, and ALP in 46.2%.
      Significant and persistent increase in liver enzyme activities was verified in
      nine patients (8.5%). Ten patients with CF (9.4%) fulfill the criteria for liver
      disease. Other causes of liver disease were excluded. The mean age of the
      patients with liver disease was 7.7 years. There was absolute predominance of the
      male sex. All the patients are without symptoms. CONCLUSIONS: The prevalence of
      liver disease associated with CF was 9.4%. The frequent and transitory
      insignificant elevations of liver enzymes are well documented in the literature.
      Its significance as a predictor of liver disease has not been determined yet.
      However, the results of this study enhance the need for longitudinal assessment
      in order to define cases of liver disease in CF.

PMID- 14647746
TI  - [Changes in placental morphology of small for gestational age newborns].
AB  - OBJECTIVE: To verify changes in placental morphology of small for gestational age
      newborns, considering that the occurrence of placental alterations is more
      frequent in small for gestational age (SGA) infants than in appropriate for
      gestational age (AGA) infants. METHODS: Fifty SGA newborns were included in a
      cross-sectional study, which involved gross anatomy and light microscopy of
      placenta, membranes and umbilical cord. An equal size sample of randomized AGA
      newborns was used. All children were born at Maternidade Terezinha de Jesus, Juiz
      de Fora-MG, between February and November, 1996. After an informed consent was
      given by the mothers, the newborns were weighted at birth with assessment of
      length and head circumference. Every child's placenta, membranes and umbilical
      cord were sent to the laboratory of histology and embryology of the Department of
      Morphology of Universidade Federal de Juiz de Fora and Department of Pathology
      and Forensic Medicine of Universidade Federal de Minas Gerais. RESULTS: Placentas
      of SGA newborns differed significantly with greater incidence of
      chorioamnionitis, placental infarction, extensive perivillous fibrin deposition
      and multiple foci of parabasal chronic villitis. They were also lighter and had
      smaller diameters. Placentary index (placental weight/newborns weight ratio) was
      also significantly greater, indicating that although both placenta and small for
      gestational age newborn presented low weight, placentas impairment was smaller.
      CONCLUSIONS: Placentas of small for gestational age newborns differed
      significantly if compared to those of adequate gestational age.

PMID- 14647747
TI  - [Assessment of pulmonary function of preterm newborn infants with respiratory
      distress syndrome at different positive end expiratory pressure levels].
AB  - OBJECTIVE: To verify the alterations of pulmonary function in preterm newborn
      infants with respiratory distress syndrome (RDS). The parameters analyzed were
      Dynamic Compliance (Cdyn), Inspiratory Tidal Volume (TVinsp), partial arterial
      pressure of carbon dioxide (PaCO2). METHODS: Eleven preterm newborn infants, with
      gestational age <35 weeks, and birth weight <2,500 g, were include in a control
      case study. All infants presented RDS and were treated with 120 mg/Kg of porcine
      surfactant. The initial positive end expiratory pressure (PEEP) was 3 cm H2O. A
      pneumotachograph with a graphical monitor was used to assess the pulmonary
      function. After each increase in the PEEP (4 and 6 cm H2O), there was an interval
      of 20 minutes before measuring the arterial data of pulmonary function and
      arterial gases. RESULTS: There were three males and eight females (1:2.7) among
      the infants with RDS. The mean gestational age was 30.78. +/- 2.05 weeks, ranging
      from 26 to 34 weeks. The increase in the PEEP from 3 to 6 cm H2O caused
      significant decrease in the TVinsp (6.46 +/- 3.43 to 4.20 +/- 2.35, P=0.0262).
      With the increase in the PEEP from 4 to 6 cm H2O, there was also a decrease in
      the TVinsp (5.98 +/- 3.33 to 4.20 +/- 2.35), (P=0.0044). Regarding the Cdyn, when
      there was an increase in the PEEP from 3 to 6 cm H2O, the reduction was
      statistically significant (0.58 +/- 0.27 to 0.46 +/- 0.25, P=0.0408) and from 4
      to 6 cm H2O, the reduction in the Cdyn was also important (0.77 +/- 0.27 to 0.46
      +/- 0.25), (P=0.0164). Increases in the PEEP from 4 to 6 cm H2O caused increases
      in the PaCO2 (52.81 +/- 15.49 to 64.90 +/- 12.69), (P= 0.0141). A more
      significant increase was observed when the PEEP was elevated from 3 to 6 cm H2O
      (41.45 +/- 7.87 to 64.90 +/- 12.69, P=0.0033). CONCLUSIONS: The study showed that
      the PEEP from 3 to 4 cm H2O produces better results in terms of Cdyn and less
      collateral effects regarding respiratory acidosis and pulmonary hyperventilation
      with impairment of the alveolar ventilation, evidenced by the increase in the
      PaCO2 and the decrease in the TVinsp.

PMID- 14647748
TI  - [Pediatric cancer: analysis of hospital records].
AB  - OBJECTIVE: To analyze pediatric cancer hospital records regarding the occurrence
      of new cases; to verify the relation between sex, age, race, origin and the
      disease clinical extension; to describe the mortality of children with cancer; to
      explore the association of new cases with proposed demographic variables, disease
      clinical extension and vital status. METHODS: Observational, descriptive,
      longitudinal study in children up to 14 years old, from Santa Catarina. Three
      hundred and seventy-one new cases of cancer were treated in a regional reference
      outpatient clinic (1994-98) and recorded according to the International
      Classification of Childhood Cancer. Multiple Correspondence Analysis was applied
      to evaluate the categorical variables. RESULTS: Three-hundred and seventy-one new
      cases of cancer were recorded with constant distribution in each year. Cancer
      affected preschoolers (41.5%) and males (55.8%). Leukemia was observed in 36.6%
      of the cases. Non-localized stage on the diagnosis occurred in 55.7%. The death
      occurred in 55.7% of the cases with non-localized disease and 16.3% with
      localized disease. At the end of the study 58.8% of the children were alive.
      CONCLUSIONS: We observed more cases of cancer at pre-school age and among male
      subjects. Leukemia is the most frequent type of cancer. Non-localized disease
      predominates on the diagnosis. The death frequency is higher in the group with
      non-localized disease. There is direct association with non-localized disease,
      living vital status, school age, adolescent age, female, and for non-localized
      disease with death vital status, infant age, pre-school age and male.

PMID- 14647749
TI  - [Acute disease of the lower airways in children under five years of age: role of
      domestic environment and maternal cigarette smoking].
AB  - OBJECTIVE: To study the prevalence of acute disease of the lower airways and the
      role of the domestic environment and maternal smoking. Among the recognized risk
      factors, passive smoking, living in crowded environments and poor housing
      conditions play a fundamental role in the causal chain of these diseases.
      METHODS: A cross-sectional study was carried out in a sample of 775 children aged
      between 0 and 59 months living in Rio Grande, southern Brazil. Trained
      interviewers applied a standardized questionnaire to the mothers or guardians of
      these children in their homes and gathered information about maternal
      characteristics, housing conditions, socio-economic status of the family and
      smoking habits. Environmental factors were individually studied, and classified
      according to a score that evaluated the intensity of their association with
      respiratory diseases. Bivariate analyses were performed, calculating the
      prevalence ratios for each risk factor, as well as multivariate ones, by means of
      non-conditional regression analyses. RESULTS: The main risks identified were:
      unfavorable environment (P<0.01), less than five years of maternal educational
      level (P=0.01), monthly family income under US$ 200 (P=0.04), crowded
      environments (P=0.02), smoking during pregnancy (P=0.03) and present maternal
      smoking (P=0.01). A thirty-year-old or older mother was identified as offering a
      protection factor (P=0.05). CONCLUSIONS: These results indicate the need to
      improve the income distribution, improve the rates of educational level, and
      combat the smoking habit, particularly concerning mothers. The programs of
      control of respiratory diseases must address these critical points that represent
      an important risk to children's health.

PMID- 14647750
TI  - [Continuous fenoterol inhalation by children with severe acute asthma: immediate
      clinical effects].
AB  - OBJECTIVE: To evaluate the alterations of heart rate, blood pressure,
      psychological aspects and oxygen saturation after continuous fenoterol inhalation
      (0.5 mg/Kg) by children with severe acute asthma. METHODS: We studied 30 patients
      with severe acute asthma who were treated at the pediatric ward of Hospital
      Universitario-UFMS. The patients inhaled 0.5 mg/Kg of fenoterol (two drops/Kg)
      during one hour. Psychological aspects, oxygen arterial saturation, heart rate
      and blood pressure were evaluated at three different moments: before, after and
      one hour after the fenoterol inhalation. RESULTS: There were 17 males (56.6%) and
      13 females (43.4%). Sleepiness was observed in 16 (53.3%), psychomotor agitation
      in one (33%) and nausea and vomiting in 12 patients (40%). The average of oxygen
      arterial saturation increased from 90.9 +/- 2.8% to 92.7 +/- 2.5% (P<0.05) after
      inhalation. There was statistically significant increase in the average heart
      rate before and after inhalation (139.5 +/- 13.5 beats/min, 166.5 +/- 11.1
      beats/min, respectively), P<0.05. A significant decrease in blood pressure rate
      was observed from 117.56 +/- 10.3 / 74.6 +/- 7 mmHg, to 107.6 +/- 11 / 63.6 +/-
      9.3 mmHg (P<0.05). CONCLUSIONS: Continuous fenoterol (0.5 mg/Kg) inhalation by
      children with severe acute asthma caused sleepiness, nausea, vomits, palpitation
      and decrease in blood pressure rate. The authors suggest that patients submitted
      to this treatment need clinical monitorship at hospital settings. Children with
      concomitant diseases such as diarrhea, vomits, and dehydration require special
      attention.

PMID- 14647751
TI  - [Sentinel lymph node in children with melanoma--case report].
AB  - OBJECTIVE: To present a case of a child who was subjected to sentinel lymph node
      biopsy for cutaneous melanoma. DESCRIPTION: A 12 year-old child with Dysplastic
      Nevus Syndrome developed melanoma on the lumbar region. The excision biopsy
      revealed a melanoma with depth of 1.5 mm. The patient was submitted to
      amplification of the margins 2 cm in all directions and the sentinel node was
      also excised. The histopathological exam did not show residual disease. Sentinel
      on exam did not show metastases either under hematoxylin-eosin stain or
      immunohistochemistry (S-100 and HMB45). Therefore, RT-PCR for tyrosinase mRNA was
      positive. The patient has been followed for twelve months without evidence of
      recurrence. COMMENTS: Childhood melanoma is rare, corresponding to less than 1%
      of malignant tumors in children. Data point to a worldwide increase in its
      incidence. Melanoma occurs in melanocytic lesions in 70% and in the remaining 30%
      it occurs de novo. Melanoma is very aggressive, so the survival depends on an
      early diagnosis. Sentinel lymph node biopsy has selected patients to complete
      lymphadenectomy. Some authors have been using this technique in childhood
      melanoma.

PMID- 14647752
TI  - [Johanson-Blizzard syndrome: the importance of differential diagnostic in
      pediatrics].
AB  - OBJECTIVE: To promote a clinical entity that could be part of differential
      diagnosis of most disorders that affect the pediatric age group. DESCRIPTION: We
      describe a Brazilian girl affected by Johanson-Blizzard syndrome and review the
      literature. COMMENTS: Johanson-Blizzard syndrome is an autosomal recessive
      condition characterized by hypoplastic alae nasi, scalp defect, deafness and
      pancreatic insufficiency with malabsorption. Looking at the major signs, this
      disorder should be considered as differential diagnosis in several pediatric
      diseases.

PMID- 14647753
TI  - [Coagulase-negative staphylococcus infection in newborns: myth or reality?].

PMID- 14647754
TI  - [BCG revaccination in schoolchildren: a pioneer study].

PMID- 14647755
TI  - [Evaluation of the hypothalamic-pituitary-thyroid axis in children with Down
      syndrome].

PMID- 14647756
TI  - [Medical errors in hospitalized patients].
AB  - OBJECTIVE: To review the current literature and to discuss medical errors in
      hospitalized patients emphasizing its incidence, predisposing factors and
      prevention mechanism. Special attention is given to medication errors and adverse
      drug events in newborn infants and pediatric patients. SOURCES: Bibliographic
      review of the current literature through electronic search in Medline data-base,
      with selection of the most relevant articles. SUMMARY OF THE FINDINGS: Even
      though most medical errors are not reported, it is important to notice that its
      incidence is greater than previously assumed. In the USA, approximately one
      million of patients/year are victims of medical errors and adverse drug events.
      Today, deaths resulting from these episodes are the fourth cause of mortality in
      the USA. In neonatal and pediatric intensive care units, where the complexity and
      frequency of technical procedures are high, medical errors are frequent. Fifteen
      percent of all admissions to a neonatal intensive care unit is followed by
      medical errors. Most of these errors occur during night shifts and include
      incorrect administration of drugs (35%) and errors regarding the interpretation
      of medical prescription (26%). Environmental factors (noise, heat), psychological
      factors (anxiety, stress) and physiologic factors (fatigue, absence of sleep)
      contribute to the occurrence of errors. Recent study shows that after working 24
      hours without sleeping, the performance of a health professional is similar to a
      legally drunk person (serum alcohol level > or =0.08%). CONCLUSIONS: Errors are
      part of human behavior. The prevention of errors should include a careful review
      of the organizational system. Medical errors should be seen as an opportunity to
      change or re-structure the system and to improve the quality of health care
      delivered and patient safety.

PMID- 14647757
TI  - [Determinant factors of anemia in children].
AB  - OBJECTIVE: To present a review about the main determining factors of anemia in
      children under 5 years old. SOURCE OF DATA: Information was used from articles
      published in indexed national and international scientific journals, technical
      books and publications from international organizations. SUMMARY OF THE FINDINGS:
      Anemia constitutes the world's nutritional problem of the greater magnitude, and
      children under 5 years old represent one of the highest risk population groups.
      As with any public health problem, the origin of anemia is multi-causal and thus
      in this article the attempt is to interpret its direct or indirect relation with
      possible determinant factors and the main concordant or discordant findings in
      epidemiological studies. Among these factors are the social and economic
      conditions, the conditions of child health care, the child's nutritional state,
      the presence of morbidity, food consumption and biological factors. The role of
      the diet is emphasized with respect to the consumption and bioavailability of
      iron, and age of the child as the main determinants. CONCLUSIONS: Bearing in mind
      the magnitude of the problem and the breadth of its risk factors reviewed in this
      study, the implementation of urgent prevention and treatment measures for iron
      deficiency anemia becomes necessary. It is important to stress that a single
      strategy may have little success if other measures are not taken simultaneously;
      the role of nutritional education being relevant, together with other implemented
      actions. Children under 2 years old and children who live in rural and deprived
      areas should be priorities in programs to combat anemia.

PMID- 14647758
TI  - [Clinical significance of coagulase-negative staphylococci isolated from
      neonates].
AB  - OBJECTIVE: To evaluate the clinical significance of coagulase-negative
      staphylococci (CNS) isolated from newborns' infections at Neonatal Unit of
      Hospital das Clinicas da Faculdade de Medicina de Botucatu. METHODS: The CNS
      strains isolated were identified and classified as clinically significant and
      contaminant, based on a series of clinical and laboratory data obtained from
      patients who stayed in the Neonatal Unit. The following data were analyzed: risk
      factors for infections, clinical evolution, abnormal blood cell counts and/or C
      reactive protein and antibiotic therapy. RESULTS: Among the 117 CNS strains
      isolated, 60 (51.3%) were classified as significant and 57 (48.7%) as
      contaminant. Among the 54 infants infected by CNS, 43 (79.6%) presented very low
      birthweight (<1,500 g). Most of the infants infected by CNS were submitted to two
      or more invasive procedures (77.8%), including use of catheter (88.9%),
      parenteral nutrition (64.8%) and mechanical ventilation (61.1%). Staphylococcus
      epidermidis was the most frequently isolated species (77.8%) and more often
      associated with infection (86.7%) than with contamination (68.4%). Other species
      of CNS, including two strains of S. haemolyticus, three strains of S.
      lugdunensis, one strain of S. simulans, one strain of S. warneri and one strain
      of S. xylosus were also isolated from infants with clinical evidence of
      pneumonia, necrotizing enterocolitis and sepsis. CONCLUSIONS: Most newborns
      infected by CNS presented important risk factors for infection onset, including
      birthweight <1,500 g, foreign body presence and previous use of antibiotics. The
      identification of CNS species constitutes a useful marker of infection, since S.
      epidermidis was the species more frequently associated with infection.

PMID- 14647759
TI  - [BCG revaccination in school children: evolution of the lesion at the vaccination
      site between 48 hours and 10 weeks].
AB  - OBJECTIVE: Cutaneous reaction after BCG revaccination has been cause of concerns
      due its magnitude. Would it be intense enough to discourage its use in school-age
      children? The objective of this study is to describe the evolution of BCG
      vaccination site between 48 hours and 10 weeks post-revaccination. METHODS: A
      descriptive cohort study was carried out involving 484 children between six and
      11 years. The subjects were vaccinated with 0.1 mL of BCG-Moreau. Erythema,
      induration, pustule, ulcer, crust and final scar were measured within 48 h, 72 h
      and weekly until the tenth week, evaluated between July and December 1987. Epi
      Info 6.0 software was utilized to analyze frequencies, means, median and standard
      deviations. RESULTS: Induration was present in 99.1% and erythema in 91.6% of 438
      children evaluated within 48 h. Pustules were observed in the first week in 26.1%
      of 479 children. The first ulcers were seen during the second week. In the tenth
      week, 69.8% of 463 children showed crusts but only 29.2% completed the healing
      process. CONCLUSIONS: BCG revaccination in school-age children causes intense and
      early reaction that can be related to Koch phenomenon, even though it does not
      present the expected reduction in the healing period. The magnitude of the
      reaction is not enough to discourage its recommendation for school-age children.
      On the other hand, it is possible that the rapid inflammatory response is an
      indication of active immune response from the first vaccination.

PMID- 14647761
TI  - [Adolescents' knowledge about adolescence, puberty and sexuality].
AB  - OBJECTIVE: The objective of this research was to evaluate the level of knowledge
      about adolescence, pubertal development and sexuality among adolescents from 10
      to 14 years old at municipal public schools in Feira de Santana-Bahia, 2000.
      METHODS: Cross-sectional study, with a randomized and proportional sample out of
      a population of 6,419 students in the municipal Public System. The level of
      knowledge was analyzed according to age, sex and educational level. Data was
      collected by means of a specific confidential questionnaire, which was pre
      tested. A scale of values (score--satisfactory, reasonable and unsatisfactory)
      was established according to the percentage and proportional number of right
      answers regarding general and specific topics. Statistical inference was
      calculated by chi-square with a significance of 5% as well as the bivariate and
      multivariate analysis, calculating the simple and adjusted prevalence, through
      stratified analysis. RESULTS: Adolescents showed unsatisfactory level of
      information about terms, particularly those at the age of 10 (69.2%) and 11 years
      (70.6%), female (61.7%) and the ones in the 4th (82.8%) and 5th (61.1%) grades.
      The level of knowledge according to sex, adjusted by age and educational level,
      showed that females are 1.3 and 1.27 times more likely to present an
      unsatisfactory level of knowledge than males. The level of knowledge according to
      educational level, adjusted by age, showed that those subjects between 4th and
      5th grades are 2.32 times more likely to present an unsatisfactory level of
      knowledge if compared to students of 6th and 8th grades, with significant
      differences (p<0.05). CONCLUSIONS: The high prevalence of unsatisfactory level of
      knowledge with significant association between 4th and 5th grades and females
      points to the necessity of educative actions regarding health and sexuality in
      the beginning of adolescence at municipal public schools.

PMID- 14647760
TI  - [Evaluation of the hypothalamic-pituitary-thyroid axis in children with Down
      syndrome].
AB  - OBJECTIVE: To determine the thyroid stimulating hormone (TSH) secretion in
      children with Down syndrome (DS), who do not present clinical and laboratory
      evidence of classical hypothyroidism and concomitant undetectable antibodies.
      METHODS: Fourteen children with DS with a mean age of 3.4 (+/- 1.8) years were
      studied. Patients with classical hypothyroidism or hyperthyroidism or those with
      positive antithyroid antibodies were excluded. The DS group was compared to a
      control group of 16 children with a mean age of 11.8 (+/- 3.8) years, diagnosed
      as having familial short stature or constitutional growth delay. Both groups
      underwent hormonal measurements at basal condition to determine serum TSH, T3,
      T4, free T4 and prolactin concentrations and after stimulation with thyrotropin
      releasing hormone (TRH). Thyroid hormones concentrations were also compared when
      children with DS were subdivided into two groups according to their basal TSH
      levels. RESULTS: Basal TSH and prolactin levels were significantly higher in DS
      group. After stimulation with TRH, TSH peak was higher in the DS group. The
      number of patients presenting basal TSH levels higher than 5 microU/mL and TSH
      peaks higher than 30 microU/mL were significantly higher in the DS group.
      CONCLUSIONS: Children with Down syndrome present frequent increase in basal TSH
      concentrations, despite the presence of normal basal thyroid hormones levels and
      negative antithyroid antibodies. Most of them (65%) show early intense response
      after TRH stimulation. Our data demonstrate that in spite of the absence of
      classic hypothyroidism and/or antithyroid antibodies, an abnormal pattern of TSH
      secretion occurred in patients with Down syndrome, possibly related to
      hypothalamic dysfunction.

PMID- 14647762
TI  - [Autoimmune hepatitis in children and adolescents: clinical study, diagnosis and
      therapeutic response].
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical, laboratory and
      histopathological characteristics and the response to immunosuppression in
      children and adolescents with autoimmune hepatitis (AIH). METHODS: The present
      research is a descriptive study consisting of 39 children and adolescents with
      AIH who receive care at the Department of Pediatric Gastroenterology of Hospital
      das Clinicas (UFMG) from 1986 to 1998. RESULTS: Children's age ranged from 1.6 to
      17 years (mean 8.7 +/- 3.49), most of them were females (87.2%). There were three
      types of clinical presentations: chronic (53.9%), acute (41%), and serious
      hepatic failure (5.1%). The most relevant laboratory parameters were the
      aminotransferases and gamma-globulin increase. Antinuclear antibodies were
      positive in 66.7% of the patients, while smooth muscle antibodies were positive
      in 52.8% and anti-LKM1 in 3% of the patients. In the histopathology the most
      important findings were the piecemeal necrosis (93.7%), moderate to severe portal
      inflammation (78.1%), definitive or incomplete cirrhosis (76.9%), absence of
      lesion of biliary ducts (93.7%) and presence of rosettes (90.6%). During the
      treatment, 77.8% obtained complete resolution, associated to side effects in
      27.8% of them. Seven patients died (17.9%). During the treatment there was
      significant z score reduction (p<0.05) for height/age. CONCLUSIONS: After
      carrying out this study, we observed that the typical characteristics of AIH
      were: female sex, several clinical presentations, increased aminotransferase, and
      hypergammaglobulinemia. Histopathology showed a predominance of incipient and/or
      definitive cirrhosis associated with moderate to severe portal inflammation and
      piecemeal necrosis. Treatment using corticosteroids and azathioprine, turned out
      to be effective. However, the reduction in the height/age z score probably
      represents an adverse effect of corticoid treatment.

PMID- 14647763
TI  - [Comparison between two methods of supplemental iron intake to prevent iron
      deficiency anemia in the first year of life of preterm infants].
AB  - OBJECTIVE: To compare 2 methods of iron supplementation (fortified formula versus
      medicinal iron drops) to prevent iron deficiency anemia in preterm infants.
      METHODS: Sixty six premature infants weighing between 1000-2000 g were included
      in the study. Forty infants completed the whole follow-up period, divided into 2
      groups: Group A: 20 infants fed with iron fortified formula (11 mg Fe/l); Group
      B: 20 infants fed powder cow's milk supplemented with 2 mg Fe/kg/day, as drops of
      ferrous sulphate. At 2 and 12 months 2 ml of blood were collected to measure
      hemoglobin, hematocrit, serum iron, TIBC, serum ferritin and free erythrocyte
      porphyrins. At the 6th month 1 ml of blood was drawn for hemoglobin and
      hematocrit determinations. Statistical analysis used the Student t test and chi2,
      with p<0.05. RESULTS: There were no significant differences between the groups in
      terms of body weight and weight gain; hemoglobin, hematocrit, serum iron levels
      and TIBC saturation indexes were similar in both groups at 2 months but
      significantly higher in Group A at 12 months of age, while free erythrocyte
      porphyrin levels remained stable in Group A and increased significantly in Group
      B (p<0.05). Ferritin levels were normal in both groups at 2 month and declined
      sharply by 1 year of age, but only 4 (20%) infants of Group A showed levels < or
      =10 ng/ml, against 12 (60%) of the Group B (p<0.02). CONCLUSIONS: The iron
      fortified formula was significantly more efficient than medicinal iron drops to
      prevent iron deficiency anemia of preterm infants.

PMID- 14647764
TI  - [Anemia in infancy: etiology and prevalence].
AB  - OBJECTIVE: To verify the prevalence of anemia, iron deficiency anemia and iron
      deficiency in infants, at a Public Health Unit in the city of Goiania-Brazil; to
      analyze and to correlate the hematologic and biochemical variables. METHODS: A
      cross-sectional study was carried out. One hundred and ten full-term infants of
      the 120 mothers interviewed were included. The infants aged between six and
      twelve months and there were not twins. Socioeconomic and hematologic data was
      obtained. Venous blood was taken from fasting infants in order to carry out a
      complete hemogram through electronic cell counting, serum iron, serum ferritin
      and C-reactive protein, which were used in the evaluation of the etiology of iron
      deficiency in the anemic infants. Children with hemoglobin <11 g/dL were
      considered anemic. RESULTS: The prevalence of anemia was 60.9%. In the diagnosis
      of the iron deficiency etiology in infants without an inflammation process, when
      considering the alteration of hemoglobin plus two more indices among mean
      corpuscular volume (MCV) or mean corpuscular hemoglobin (MCH) or serum ferritin
      or serum iron, the prevalence of the iron deficiency was 87%. Nevertheless, when
      red cell distribution width (RDW) was included in the indices, the prevalence was
      97.8%. In the non-anemic infants, considering ferritin and RDW, the prevalence of
      iron deficiency observed was 28%. The best correlation among hematologic and
      biochemical variables were between hemoglobin and hematocrit (r=0.946), and MCH
      with MCV (r=0.950). CONCLUSIONS: The main etiology in infants was iron deficiency
      anemia and its prevalence varied according to different parameters and criteria.

PMID- 14647765
TI  - [Iron, copper and zinc in adolescents during pubertal growth spurt].
AB  - OBJECTIVE: To examine iron, copper and zinc nutritional status and their
      correlation with Body Mass Index (BMI), serum and dietetic levels in adolescents
      during the pubertal growth spurt. METHODS: A descriptive cross-sectional study
      involving a sample of 47 adolescents out of 360 patients (19 boys, whose ages
      ranged from 12.3 to 16 years and 28 girls, whose ages ranged from 11.1 to 13.6
      years), who were seen at a clinic for adolescents from March to December 1999.
      The variables analyzed were: Diet (24 hours Dietary Recall, Food Frequency Intake
      Questionnaire and Food Register Methods) to determine iron, copper and zinc
      intake; anthropometry (weight and height) to check BMI; biochemistry (measure of
      serum iron level through a Diagnostica kit in vitro; ferritin through Immulite
      kit, and atomic absorption spectrophotometry for biochemical evaluation of serum
      iron, ferritin, copper and zinc. Spearman coefficient correlation was used for
      statistical analysis. RESULTS: Forty seven adolescents during pubertal growth
      spurt showed adequate ingestion: iron (95% and 36%), copper (53% and 57%) and
      zinc (21% and 21%) in males and females, respectively. Most of them were
      eutrophic according to the BMI percentiles. Biochemically, boys presented normal
      values for serum iron and zinc in the whole sample, 95% for copper and 84% for
      ferritin. Girls also presented normal values for iron and zinc values in the
      whole sample, 96.4% for copper and 96% for ferritin. There were no statistically
      significant correlation between BMI and serum Fe, ferritin, Cu and Zn
      concentrations and between serum concentration and dietetic ingestion of the
      studied minerals, neither between serum iron and ferritin. CONCLUSIONS: It is not
      clear if serum levels of Zn and Cu are floating during the growth process or if
      each adolescent has a stable level of these minerals during the pubertal growth
      spurt. Normal Fe, Cu and Zn serum levels in most adolescents evaluated may
      reflect the organism ability to accomplish homeostatic adjustments.

PMID- 14647766
TI  - [Overweight and obesity prevalence among children and adolescents from Northeast
      and Southeast regions of Brazil].
AB  - OBJECTIVE: To study the prevalence of obesity and overweight among children and
      adolescents from Northeast and Southeast regions of Brazil. METHODS: Data was
      collected form Life Pattern Research conducted by the Brazilian Institute of
      Geography and Statistics (IBGE) in 1997. A sample of 3,317 children and 3,943
      adolescents was studied according age groups. Overweight (adolescents) and
      obesity (adolescents and children) were defined according to World Health
      Organization recommendations. Z-test was used to compare prevalence among age
      groups, sex and geographic region. The cut-off point for statistical significance
      was 0.05. RESULTS: Overweight prevalence in adolescents was 1.7% in Northeast and
      4.2% in Southeast. Obesity prevalence in adolescents was 6.6% and 8.4% in
      children and 8.2% and 11.9% in Northeast and Southeast, respectively. Considering
      both regions prevalence of obese female children was 10.3%, the rate of obese
      adolescents was 9.3% and overweight adolescents represented 3.0%. Among males
      prevalence was 9.2%, 7.3% and 2.6%, respectively. CONCLUSIONS: Obesity prevalence
      is lower in Northeast than Southeast among children with age from 2 to 17 years
      old. Overweight prevalence among adolescents was also lower in Northeast than in
      Southeast. The prevalence of obesity among younger than 2 and older than 18 years
      old was the same. Obesity prevalence is higher among breast-fed females. Among
      other age groups prevalence of obesity and overweight was the same for males and
      females. It is difficult to compare these results with other studies, since there
      are few populational studies and the criteria used to define overweight and
      obesity in children and adolescents varies in each study.

PMID- 14647767
TI  - [Factors related to the post-portoenterostomy prognosis of biliary atresia].
AB  - OBJECTIVE: This study considered the presence of congenital anomalies, ductal
      plate malformation, area of fibrosis and, mainly, the patient's age in cases of
      biliary atresia submitted to surgery. The present study verified the influence of
      these factors on the follow-up of a biliary atresia sample. METHODS: A sample of
      47 patients with biliary atresia was evaluated in a cross-sectional study. Their
      histologic specimens were stained for antibody anticytokeratin 19 and CAM 5.2
      through immunohistochemistry in order to study biliary structures, and for
      picrosirius red to evaluate the area of fibrosis. The study of biliary structures
      was performed by two pathologists and the first author of the study. They were
      "blind" with regard to the clinical follow-up. The area of fibrosis was
      quantitatively evaluated. Data on the patients with regard to age, death and
      occurrence of liver transplantation were searched on the patients records.
      RESULTS: Age at portoenterostomy varied between 24 and 251 days of life (90.4 +/-
      44.8 days) and follow-up was available in 32 cases (72%). The nine cases (19%)
      with extrahepatic congenital anomalies associated to biliary atresia did not
      present different prognosis from the remaining patients. Age at portoenterostomy
      influenced the prognosis (p=0.016). The area of fibrosis was different on
      patients aged less than 60 days and those aged more than 90 days at
      portoenterostomy (p=0.023), but did not influence the prognosis. The presence of
      ductal plate malformation, as well, did not influence the follow-up. CONCLUSIONS:
      Age at portoenterostomy was the only factor that influenced prognosis on this
      sample of biliary atresia. It is necessary to increase the biliary atresia sample
      to check the influence of congenital extrahepatic anomalies on the follow-up post
      portoenterostomy.

PMID- 14647768
TI  - [Bronchovascular fistula--complication of percutaneous central venous catheter in
      a neonate].
AB  - OBJECTIVES: To present a case of central venous line misplacement with vasculo
      pulmonary fistula and severe respiratory consequences in a newborn. To review the
      literature concerning respiratory and non-respiratory complications related to
      the introduction of percutaneously placed central venous lines in children.
      REPORT: Evaluative and diagnostic data were described after patient chart review.
      A premature newborn was admitted in a NICU after delivery for treatment of low
      grade hyaline membrane disease and infection manifested afterwards. In the day
      after the introduction of the percutaneously placed central venous catheter, in
      order to provide parenteral nutrition, respiratory distress began with rapid
      progression. Mechanical ventilation was demanded to establish proper gas
      exchange. The complication was revealed after checking the catheter course using
      radiographic contrast. COMMENTS: Complications associated with central venous
      catheter insertion are not rare and infection is the most frequent one. It is
      essential that the caretakers be aware of the many less frequent ones like
      vascular thrombosis and catheter misplacement with organ injury and extravascular
      fluids collections. Only one description related to this kind of complication
      verified in our patient was found in newborns. This singular characteristic may
      have resulted in embarrassment for rapid diagnosis. Care related aspects, after
      catheter insertion, that could make easier the prompt recognition of these
      complications are emphasized.

PMID- 14647769
TI  - [National Network of Human Milk Banks in Brazil: first class technology].

PMID- 14647770
TI  - [Breastfed infants with chronic idiopathic constipation: a problem to be
      studied].

PMID- 14647771
TI  - [Ophthalmological examination in newborns: a necessary routine].

PMID- 14647772
TI  - [Insulin pen injector for the treatment of type 1 diabetes mellitus].
AB  - OBJECTIVE: The objective of this review was to evaluate the medical literature in
      the last ten years comparing the use of insulin pen injectors versus insulin
      syringes in children with type 1 diabetes. SOURCES: This is a review of
      literature in the last ten years based on Medline. SUMMARY OF THE FINDINGS: The
      use of the insulin pen injector is disseminated all over the world. Most studies
      show that this method is more comfortable and makes patients' life easier. It is
      associated to better glycemic control, it is more easily accepted and is related
      to the reduction of hypoglycemic crisis. The use of the insulin pen injector
      provided better quality of life to this group of patients. CONCLUSIONS: The new
      technology produces different methods of insulin administration trying to improve
      the quality of life of diabetic patients and to reduce the risks of short term
      complications through the use of insulin pen injectors. The effects of this kind
      of insulin delivery with the aim of preventing chronic complications are not well
      established.

PMID- 14647773
TI  - [Alternative test for detection of coliforms bacteria in manually expressed human
      milk].
AB  - OBJECTIVE: To compare an alternative method to the most probable number (MPN)
      test for the detection of total coliform present in manually expressed human
      milk. METHODS: 343 samples of manually expressed human milk from flasks donated
      to the Human Milk Bank of Instituto Fernandes Figueira--IFF were sent to the
      Laboratory of Food Control of IFF. The samples were used for comparing both
      methods, i.e., the most probable number (MPN) method, as described in the
      "Standard methods for the examination of dairy products", and the alternative
      method. RESULTS: Coliforms were detected in 31.2% of the samples analyzed, with
      populations ranging from 3.0 x 10(0) to 1.1 x 10(4) total coliform MPN/mL. The
      comparison between classical and alternative methods showed similar results
      regarding the presence of coliform microorganisms in expressed human milk
      samples. The alternative method detected the presence of total coliform in all
      contaminated and in four noncontaminated samples according to the MNP method.
      CONCLUSIONS: The alternative test allows the detection of the presence or absence
      of coliforms and it is useful for the quality control of pasteurized flasks
      containing manually expressed human milk manipulated at human milk banks.
      Therefore, we conclude that the alternative test can be used in the routine of
      human milk banks as a substitute for the MNP method, since its cost is equivalent
      to 1/7 of the cost of the traditional method.

PMID- 14647774
TI  - [Contamination of expressed human milk by mycelial fungi].
AB  - OBJECTIVE: To characterize the genera of mycelial fungi detected in expressed
      human milk received at the human milk bank of Instituto Fernandes Figueira after
      home collection. METHODS: We studied 821 expressed human milk samples randomly
      obtained from flasks filled by the donors at home. The possible presence of
      molds, yeasts and mesophilic microorganisms was investigated. A total of 48
      strains of mycelial fungi were isolated from the human milk bank samples and
      identified through standard laboratory techniques. RESULTS: Microbiological
      analysis revealed the occurrence of molds and yeasts in 43 samples (5.2%), with
      counts reaching 10(3) CFU/ml. The following microorganisms were identified:
      Aspergillus niger group (6.3%), Aspergillus sp. (4.2%), Paecilomyces sp. (12.6%),
      Penicillium sp. (60.4%), Rhizopus sp. (2.0%), and Syncephalastrum sp. (14.5%).
      Four samples showed the presence of more than one mycelial fungus type.
      CONCLUSIONS: The presence of molds and yeasts in human milk manually expressed at
      home suggests that the hygiene conditions of the collection site may contaminate
      milk. Thus, when hospitalized premature babies receive the raw product, it is
      very important to observe the collection, storage and transport conditions in
      order to avoid the presence and consequences of contaminants increase.

PMID- 14647775
TI  - [Constipation in infants: influence of type of feeding and dietary fiber intake].
AB  - OBJECTIVE: To study the relationship between breast-feeding, dietary fiber intake
      and constipation in infants. METHODS: The study population consisted of 275
      infants consecutively enrolled in two Primary Care Clinic in the city of Embu, in
      the Great Sao Paulo. The feeding pattern were classified in predominantly breast
      feeding, partially breast and cow's milk feeding and artificial feeding.
      Constipation was defined by the elimination of hard stool associated with one of
      the following: painful or difficult defecation, hard or round cracked stools and
      less than three defecations a week. False constipation was defined by the
      elimination of soft stools without pain or difficulty but with less than three
      defecations a week. RESULTS: Constipation was found in 25.1% (69/275). False
      constipation was found only in the first semester of life in 5.1% of 159 infants.
      The prevalence of constipation was higher between 6 and 24 months (38.8%, 45/116)
      than in the first semester of life (15.1%, p=0.000). A model of logistic
      regression demonstrated that infants under artificial feeding were 4.53 times
      more liable to develop constipation than infants who were predominantly
      breastfed. The daily dietary fiber intake (g/day) was similar (p=0.57) among the
      constipated (median=9.0 g; 25th and 75th percentiles: 6.9-13.1 g) and non
      constipated (median=8.8 g; 25th and 75th percentiles: 6.1-12.9 g). CONCLUSIONS:
      Dietary fiber intake was similar in constipated and non-constipated infants.
      Breast-feeding serves as a protection factor against the development of
      constipation in the first semester of life.

PMID- 14647777
TI  - [Lactose malabsorption in children and adolescents: diagnosis through breath
      hydrogen test using cow milk].
AB  - OBJECTIVE: To determine the prevalence of lactose malabsorption and its
      association with skin color and age in children and teenagers attending public
      schools in Porto Alegre, Brazil. METHODS: A cross-sectional study was performed
      with 225 subjects between 8 and 18 years attending two public schools in Porto
      Alegre, Brazil. Patients were randomly selected. Subjects were classified
      according to skin color (white and non-white) and age group (8 to 12 and 13 to 18
      years). Lactose malabsorption was diagnosed using the breath hydrogen test after
      ingestion of 250 ml of whole cow milk. The test lasted for 3 hours, with
      collections after fasting and 60, 120, and 180 minutes after milk ingestion.
      Malabsorption was determined in the presence of increase of > or =20 ppm in
      hydrogen concentration regarding the basal levels. RESULTS: Two-hundred and
      twenty-five students were studied, with a mean age +/- standard deviation of 12.2
      +/- 2.0 years. The subjects consisted of 134 females (59.6%); 154 white (68.4%);
      and 71 nonwhite. Lactose malabsorption was observed in 19/225 cases (8.4%). It
      was diagnosed in 8/154 white patients (5.2%) and in 11/71 non-white patients
      (15.5%) (p=0.02). Regarding the age group, we found 15/143 cases of malabsorption
      in students between 8 and 12 years (10.5%), and 4/82 cases in students between 13
      and 18 years (4.9%) (p=0.227). CONCLUSIONS: The prevalence of lactose
      malabsorption in students attending public schools in Porto Alegre is
      significant, especially if we consider that the physiological doses (250 ml of
      milk) were used for diagnosis. The malabsorption rate was higher among non-white
      children, which confirms the influence of race on primary adult type
      hypolactasia. No association was observed between lactose malabsorption and age
      group.

PMID- 14647776
TI  - [Importance of the ophthalmological evaluation in newborns].
AB  - OBJECTIVE: To verify the existence of ocular diseases in the first 48 hours of
      life of newborns and relate it to the clinical suspicious of pediatricians.
      METHODS: A prospective study was performed. All infants that were born between
      July and December of 2000 were evaluated in the nursery of Hospital Universitario
      Evangelico de Curitiba (HUEC). Six hundred sixty-seven newborns were evaluated
      through a protocol by residents and tutors of ophthalmology, regardless of
      pediatricians suspicious of ocular disorder. The examination consisted of
      inspection, oblique illumination, evaluation of ocular deviation and direct
      ophthalmoscopy (red reflex) in all patients. RESULTS: Among all examined
      newborns, 3.75% showed some ocular disease. The most frequent problem was corneal
      opacity. The ocular diseases were not noticed by pediatricians, neonatologists
      and parents in fifty-six per cent of the cases presenting some problem.
      CONCLUSIONS: This study showed that many ocular disorders presented at birth are
      not noticed by pediatricians (56%), which highlights the importance of
      ophthalmological evaluation in all newborns as a routine examination in the first
      48 hours of life.

PMID- 14647778
TI  - [Weight/length ratio: is it a good index to assess the nutritional status of full
      term newborns?].
AB  - OBJECTIVE: An accurate assessment of the nutritional status of an infant at birth
      is very important, since it provides information on early identification of
      pathological events related to intrauterine growth acceleration or retardation.
      Anthropometric ratios such as weight/length and mid-arm circumference/head
      circumference may be used as alternative tools for this purpose. The main
      objective of this study was to verify the correlation between triceps skinfold
      thickness with Rohrer Index, Body Mass Index, weight/length ratio, and mid-arm
      circumference/head circumference ratio. METHODS: A cross-sectional study was
      carried out with 390 full-term newborns delivered at the Maternity Ward of
      Instituto Materno Infantil of Pernambuco, from May to July 1999. The newborns had
      their birthweight, length, head and mid-arm circumferences and triceps skinfold
      thickness measured. RESULTS: The results showed that among the anthropometric
      indices studied the weight/length ratio showed the strongest correlation with
      triceps skinfold thickness (r=0.63, p<0.001) followed by mid-arm
      circumference/head circumference ratio (r=0.59, p<0.001). Rohrer index showed the
      weakest correlation (r=0.43, p<0.001). Multiple linear regression analyses
      revealed that weight/length ratio correlated best with skinfold thickness.
      CONCLUSIONS: We concluded that among the studied indices, weight/length ratio
      showed to be the best alternative to assess the nutritional status of infants at
      birth.

PMID- 14647779
TI  - [The use of CRIB score for predicting neonatal mortality risk].
AB  - OBJECTIVE: To examine the clinical risk index for babies (CRIB) predictive value
      for hospital death; to identify the score variable with the best predictive value
      and to compare CRIB score capability to predict hospital mortality to birth
      weight, gestational age and base excess. METHODS: CRIB score was obtained through
      a prospective way from 100 newborns with birthweight of 1,500 g or less or
      gestational age less than 31 weeks, who were admitted consecutively to the
      Neonatal Unit of Hospital das Clinicas, Universidade Federal do Parana. RESULTS:
      Fifty-five newborns were females and 45 were males, the average birthweight was
      1,078 +/- 0.277 g and gestational age was 29.2 +/- 2.8 weeks. Twenty-one patients
      died. The mortality rate in the CRIB groups 1, 2, 3 and 4 was, respectively 6.6%;
      46.2%; 87.5% and 100.0%. The score accuracy for mortality was confirmed (area
      under the ROC curve=0.877) and the best score variable to predict hospital death
      was maximum base excess (area under the ROC curve=0.795). Compared with
      birthweight and gestational age, CRIB was significantly better to predict
      mortality. CONCLUSIONS: Besides being useful to predict hospital death, CRIB was
      a simple score to be applied. Based on these results, we recommend its inclusion
      in the routine of neonatal units.

PMID- 14647780
TI  - [Growth of small for gestational age preterm infants].
AB  - OBJECTIVE: To describe the linear growth and growth velocity of preterm infants
      born small for gestational age according to variables such as weight, length and
      head circumference, from birth to three months of corrected age. METHODS:
      Prospective study of one hundred preterm infants born small for gestational age
      from 28 to 36 weeks after birth and classified as small according to the weight
      for their gestational age. The anthropometric data was obtained at birth, and
      continued to be measured weekly until the probable delivery date and monthly
      until three months of corrected age. Growth curves were calculated according to
      the mean values adjusted by the polynomial function of Count model. RESULTS: The
      infants' growth curves for the three variables were much below the ones of the
      preterm infants with adequate size for gestational age until the fortieth week.
      However, the head circumference growth reached the 10th percentile curve of the
      NCHS at the fortieth week, and the 25th percentile at three months of corrected
      age. The weight growth curve reached the 10th percentile curve around one month
      and a half for males and two months and a half for females. The length growth
      curve reached the 10th percentile for males at three months of corrected age and
      it almost reached that percentile for females after the same period of time.
      CONCLUSIONS: A tendency of recovering weight and length related to preterm
      infants with adequate size and term newborns was observed. The head circumference
      showed an obvious and early recovery.

PMID- 14647781
TI  - [Intercellular adhesion molecule-1 serum profile in cardiac postoperative period
      of infants undergoing cardiopulmonary bypass].
AB  - OBJECTIVE: To measure the intercellular adhesion molecule-1 serum levels at
      baseline and after cardiopulmonary bypass exposure in infants undergoing surgery
      of congenital heart disease. METHODS: Contemporary cohort study, which consisted
      of 21 infants undergoing cardiac surgery with cardiopulmonary bypass. The
      intercellular adhesion molecule-1 serum levels were measured at induction of
      anesthesia, at the end of cardiopulmonary bypass, and 8 hours and 26 hours after
      cardiopulmonary bypass. The samples were measured using ELISA. RESULTS:
      Atrioventricular septal defects and tetralogy of Fallot were the most common
      congenital cardiac pathologies. The age and weight mean values were 6.6 months
      and 5.8 Kg. The median values of cardiopulmonary bypass time and aortic cross
      clamping time were 87 minutes and 53 minutes. All infants used inotropic drugs.
      The median values of intubation time and length of stay were 72 hours and 21
      days. The patients' mortality rate was 9.5%. The baseline levels of the molecule
      were higher than the normal values (P<0.0001). The levels of the molecule
      significantly decreased at the end of the cardiopulmonary bypass (P<0.001),
      significantly increasing 8 hours after that period (P<0.005), without reaching
      baseline values 26 hours after that. CONCLUSIONS: The soluble intercellular
      adhesion molecule-1 baseline serum level is higher than normal in infants
      presenting congenital cardiac defects. This molecule serum levels vary after
      cardiopulmonary bypass exposure, presenting a characteristic behavior in these
      patients.

PMID- 14647782
TI  - [Vascular rings in childhood: diagnosis and treatment].
AB  - OBJECTIVE: To present the study carried out by the Pediatric Surgery Department
      of Instituto da Crianca at the Medical School of Universidade de Sao Paulo
      regarding the diagnosis and treatment of children with aortic arch abnormalities
      and to define the role of complementary exams for diagnosis. METHODS:
      Retrospective study of 22 patients with diagnosis of tracheoesophageal
      compression treated at Instituto da Crianca from 1985 to 2000, analyzing pre- and
      postoperative clinical data, diagnostic exams and outcome. RESULTS: The most
      frequent diagnosis was right aberrant innominate artery (10 cases), followed by
      double aortic arch (7 cases) and right aortic arch (5 cases). Respiratory
      symptoms (86%) and early manifestation (76% since the neonatal period) were
      predominant. Nevertheless, most cases (60%) had the definitive diagnosis
      established only after 1 year of life. The most relevant examination for the
      diagnosis was the esophagogram. The correction of all the anomalies was carried
      out through left postero-lateral thoracotomy. There were no surgical
      complications. The outcome was worse in patients with delayed treatment. All
      children remained symptomatic for up to 6 months, although they had significant
      improvement in the postoperative period. CONCLUSIONS: The diagnosis of vascular
      rings should be considered in children with early respiratory symptoms and in the
      wheezing baby with difficult control. The diagnosis may be established just
      through the esophagogram. Other image studies add few information and they are
      unnecessary in most cases. Less severe symptoms may persist for variable periods.

PMID- 14647783
TI  - [Liddle's syndrome: late diagnosis of a rare cause of arterial hypertension].
AB  - OBJECTIVE: The aim of this article is to highlight the importance of a rare
      disease that causes severe arterial hypertension in children. It is important to
      advise pediatricians to measure arterial pressure in children in order to avoid
      late diagnosis and renal insufficiency. DESCRIPTION: We report a case of a 13
      year-old patient that presented typical clinical and laboratorial features of
      Liddle's syndrome. The diagnosis was established based on the clinical picture
      associated with the presence of chronic hypokalemia, increase of urinary
      potassium excretion with sodium retention and reduction of renin plasma activity,
      and circulating levels of angiotensin II and aldosterone. In a spite of the
      initial therapeutic response to triamterene, the patient developed progressive
      renal failure due to the delay in the diagnosis and the poorly controlled
      hypertension. COMMENTS: Liddle's syndrome consists of a form of
      pseudoaldosteronism characterized by arterial hypertension, hypokalemia,
      metabolic alkalosis and failure to thrive. Some aspects regarding
      physiopathology, diagnosis and treatment are discussed.

PMID- 14647786
TI  - [Injury prevention and control: will we or will we not step out of the twentieth
      century?].

PMID- 14647787
TI  - [Penicillin susceptibility of Streptococcus pneumoniae in Brazil: the tip of the
      iceberg].

PMID- 14647788
TI  - [Nutritional status and breath hydrogen test with lactose and lactulose in
      children].

PMID- 14647789
TI  - [Ischemic heart disease: prevention should begin in childhood].
AB  - OBJECTIVE: To review the main risk factors for ischemic heart disease and
      preventive strategies during childhood. SOURCES: Medline review between 1985 and
      2001, and key references from the studies evaluated. CONCLUSIONS: Preventive
      interventions that may start in childhood are described for risk factors such as
      hyperlipidemias, obesity, smoking and systemic hypertension. Results of early
      diagnosis and efficiency of interventions are discussed. Recent studies have
      shown that life styles potentially associated with atherosclerosis begin during
      childhood. Thus, early intervention regarding these life styles could have impact
      on adult behavior, reducing the prevalence of this pathologic condition.

PMID- 14647790
TI  - [Risk factors for accidental injuries in preschool children].
AB  - OBJECTIVE: To measure the main risk factors associated with the occurrence of
      accidental injuries in children aged 4-5 years. METHODS: The study included a
      prospective cohort of children whose parents filled in a diary recording
      accidents and injuries during a period of one-month. The children represented a
      systematic subsample from a population-based birth cohort in southern Brazil. The
      outcome was the number of reported injuries per child during one month.
      Multivariate analysis (Poisson regression) was used to assess confounding
      factors. RESULTS: The monthly frequency of accidents was 53.8%, and 48.4% of the
      children suffered at least one injury. Boys had 30% more injuries than girls, and
      white children had 70% higher incidence than non-white. Family income, parental
      education and maternal employment were not associated with the frequency of
      injuries. After adjustment of socioeconomic and environmental factors, having
      younger siblings was associated with a 30% higher injury rate, and living in a
      home made of bricks was associated with a 35% increase. The incidence of injuries
      appeared to be higher among children attending day-care centers and those living
      in periurban areas. CONCLUSIONS: Few risk factors were associated with an
      increased frequency of injuries. Among them, the most amenable to intervention
      seems to be the presence of younger siblings. Parents should become aware of
      children's needs for increased attention when a younger sibling is born.

PMID- 14647791
TI  - [Nasopharyngeal isolates of S. pneumoniae from healthy carriers and children with
      pneumonia: colonization rates and antimicrobial susceptibility].
AB  - OBJECTIVES: To compare colonization rates and antimicrobial resistance of
      nasopharyngeal pneumococci in healthy carriers and children with pneumonia.
      METHODS: A cross-sectional study. Healthy subjects of this study were selected
      from randomly chosen immunization centers and day-care centers, and those with
      pneumonia were selected in pediatric emergency rooms. Flexible perinasal alginate
      swabs were employed to collect nasopharyngeal pneumococci specimens. Isolation
      and identification were performed according to standard procedures. Minimum
      Inhibitory Concentrations were assessed by microdilution techniques. RESULTS: We
      studied 911 children, 429 healthy controls (60% of carriers, 72% attending day
      care centers and 49% recruited in immunization centers) and 482 children with
      pneumonia (50% of carriers) (P=0.02). The Minimum Inhibitory Concentration of
      penicillin to 441 isolates detected 198 (45%) of intermediate and 16 (4%) fully
      resistant pneumococci. Antimicrobial resistance rates of isolates from healthy
      carriers and children with pneumonia were, respectively: penicillin 48% (37% for
      immunization centers and 55% for day-care centers) and 50% (P>0.05), erythromycin
      28% and 19% (P=0.05); cotrimoxazole 81% and 76% (P>0.05), chloramphenicol 6% and
      7% (P>0.05), rifampin 5 and 3% (P>0.05) ceftriaxone 2 and 4% (P>0.05) and
      vancomycin 0% in both groups. An association among pneumococcal resistance to
      penicillin, erythromycin and cotrimoxazole was detected. CONCLUSIONS:
      Pneumococcal carriage rate was higher in healthy children than in children with
      pneumonia. Penicillin and cotrimoxazole resistance rates were high, especially
      among those attending day-care centers.

PMID- 14647792
TI  - [Nutritional status and breath hydrogen test with lactose and lactulose in Terena
      Indian children].
AB  - OBJECTIVE: To evaluate the nutritional status, absorption and tolerance of
      lactose and the occurrence of small-bowel bacterial overgrowth. METHODS: A cross
      sectional study including all 264 Terena Indian children younger than 10 years
      from two tribes (Limao Verde and Corrego Seco) in Mato Grosso do Sul. The
      nutritional status was assessed based upon weight and height, using NCHS data as
      reference. The breath hydrogen test after an oral lactose (18 g) administration
      was used for evaluation of lactose absorption and tolerance. The occurrence of
      bacterial overgrowth was evaluated using the breath hydrogen test after the
      administration of lactulose (5 g). RESULTS: The median z scores of weight-for
      age, weight-for-height and height-for-age were, respectively, in infants under 1
      year (n=34): -0.66, +0.60 and -0.85. Between 1 and 5 years (n=111), the values
      were: -0.50, +0.28 and -1.17. Between 5 and 10 years (n=119), these
      anthropometric values were, respectively: -0.09, +0.50 and -0.60. Deficient
      lactose absorption or malabsorption was verified only after the fourth year of
      age in 89.3% of the 197 evaluated children. Lactose intolerance was found in
      37.1% of them. Small-bowel overgrowth was detected in 11.5% of the Terena Indian
      children (n=252). CONCLUSIONS: The prevalence of recent malnutrition was low, but
      the median height-for-age was lower than the NCHS reference. The prevalence of
      ontogenetic lactase deficiency was high. Bacterial overgrowth may be considered
      as evidence of the occurrence of nonsymptomatic environmental enteropathy in
      Terena Indian children.

PMID- 14647793
TI  - [Visceral leishmaniasis: clinical and laboratorial aspects].
AB  - OBJECTIVE: To compare the clinical and laboratorial data before and after the
      treatment of patients with visceral leishmaniasis admitted to a pediatric
      hospital in a nonendemic area, highlighting the importance of recognizing
      visceral leishmaniasis in pediatric patients. METHODS: Clinical, laboratorial and
      treatment data of 78 patients with visceral leishmaniasis were evaluated from
      1981 to 1992. We analyzed the average level of hemoglobin, leukocyte, neutrophil,
      platelet, albumin, gammaglobulin, class and subclass of immunoglobulin, size of
      the liver and spleen during the pre- and post-treatment using the paired t test.
      RESULTS: We included 78 patients with visceral leishmaniasis, 44 males, with age
      ranging from 8 months to 13.5 years. Sixty-one patients were from Bahia. Fever
      and splenomegaly were present in 96.1% and 100% of the cases, respectively. The
      parasitological diagnosis was obtained in 74/78 patients: 67 patients through
      smear and/or culture of bone marrow (85.7%), five through liver biopsy and two
      through spleen puncture. The hematological findings and serum albumin presented
      significant improvement at the end of treatment (P<0.001), differently from serum
      gammaglobulin levels (P=0.087). There was predominance of IgG1 subclass, with two
      patients presenting low levels of IgG2. Initial treatment used antimoniate in 67
      cases and amphotericin B in five. Eleven patients (15.7%) needed a second
      treatment, and were considered cured after it. There was significant improvement
      in the liver and spleen size at the end of the treatment (P<0.001). One patient
      presented spontaneous remission and five died due to bleeding. CONCLUSIONS: In
      order to obtain accurate diagnosis and treatment, especially regarding health
      services of areas with low-incidence of visceral leishmaniasis, the diagnosis of
      patients with fever and visceromegaly, who come from endemic areas, should
      include visceral leishmaniasis.

PMID- 14647794
TI  - [Behcet's disease in childhood].
AB  - OBJECTIVE: To make Pediatricians aware of the fact that they must investigate
      Behcet's disease while performing differential diagnosis of recurrent aphthous
      stomatitis, even though it is a vasculitis of rare occurrence in early life.
      METHODS: Between June 1996 and December 2000, we retrospectively evaluated seven
      patients of our Pediatric Rheumatology Unit. Demographic, clinical, and
      laboratory data as well as data regarding treatment and follow-up were presented.
      RESULTS: Five out of seven patients were female (71.4%), four were non-Caucasian
      (57.1%), the mean age at onset was 8 years and 11 months (variation of 6 months
      to 13 years and 8 months), the mean period until diagnosis was 2 years and 3
      months (variation of 2 months to 8 years) and the mean follow-up period was 4
      years and 2 months (three patients without follow-up). The major criteria of
      diagnosis were: oral ulcers in seven patients (100%), genital ulcers in three
      patients (42.8%), ophthalmic alterations in four patients (57.1%) cutaneous
      vasculitis in one patient (14.2%) and positive pathology test in one patient
      (14.2%). The minor criteria were: arthralgia/arthritis in five patients (71.4%),
      family history in two patients (28.5%), and sagittal sinus thrombosis in one
      patient (14.2%). The initial symptoms included recurrent aphthous stomatitis
      (more than three painful aphthous ulcers episodes in the period of 1 year),
      genital ulcers, arthralgia, fever and weight loss. The laboratory findings were:
      mild anemia in 1/6 patients, ESR>25 in 3/6 patients, increased serum
      gammaglobulin level in 2/4 patients, B5 histocompatibility antigen in 2/7
      patients. The treatment included corticosteroids for 5/7 patients (4 oral, 1
      intravenous and one local use), thalidomide for 4/7 patients, colchicine for 2/7
      patients and dapsone for 1/7 patient. The outcome was favorable in 4/6, and 3/6
      patients presented relapse. CONCLUSION: Our results confirm the importance of
      considering the diagnosis of Behcet's disease in patients with recurrent oral and
      genital ulcers.

PMID- 14647795
TI  - [Pulmonary blood flow distribution in acute viral bronchiolitis].
AB  - OBJECTIVE: To assess lung perfusion patterns in inpatients with acute viral
      bronchiolitis using quantitative 99mTc-MAA scintigraphy so as to establish an
      association with clinical and radiological findings. METHODS: A comparative,
      prospective case series study with a focus on diagnosis was carried out in a
      population of patients with acute viral bronchiolitis admitted to Hospital de
      Clinicas de Porto Alegre. Inclusion criteria were age between 1 and 24 months and
      first sudden-onset wheezing episode, suggesting bronchiolitis. The patients in
      the study were submitted to clinical, radiological and 99mTc-MAA lung perfusion
      evaluation during the first 24 hours of admission. Statistical analysis employed
      t test, taking into consideration a significance level of 0.05. RESULTS: The
      regional distribution of lung blood flow in the 38 patients studied was more
      pronounced in the upper section of the left lung in relation to the right lung
      (P<0.001). The distribution gradients of blood flow between the upper and middle
      and upper and lower sections were higher in the left lung (P<0.001). The
      distribution gradients of blood flow between the middle and lower sections were
      higher in the right lung, but without significance. The distribution gradient of
      the pulmonary flow in the anteroposterior axis was >1.0 in the upper and middle
      sections of both lungs. In the lower section it was >1.0 only in the right lung
      (P<0.007). There was no association between lung blood flow distribution patterns
      and clinical or radiological findings. CONCLUSION: There was no evidence of an
      association between lung blood flow distribution and ventilation-perfusion ratio
      in hospitalized infants with acute viral bronchiolitis; only a tendency to
      redirect lung blood flow towards upper lung sections was observed.

PMID- 14647796
TI  - [Evaluation of the understanding level of pediatric prescription].
AB  - OBJECTIVE: This study intends to establish the relation between the understanding
      level of pediatric prescription by the mother, or other adult, accompanying the
      child to a doctors visit and the probable causes of noncompliance with the
      treatment, in order to improve the quality of pediatric health care. METHODS: We
      randomly interviewed one hundred adults who accompanied children to the pediatric
      outpatient clinic of Hospital Universitario. They received medical orientation
      and/or prescriptions. The interviews were made from April to October 2000 and we
      used a questionnaire to evaluate social, economic and cultural status. We also
      evaluated aspects related to the appointment and treatment, and the understanding
      of doctors handwriting and prescription. RESULTS: Eighty-three percent of them
      received a prescription and 17% received only orientation; 88% were the mothers
      and 63% had not finished elementary school. Concerning the appointment, 80% felt
      satisfied. Seventy-one percent among those who received prescriptions could
      understand the doctor's handwriting and 29% had some or none understanding of it.
      Forty-seven percent of the prescriptions had symbols and/or abbreviations that
      could not be understood by 59% of the adults. Seventy-one percent could remember
      all the prescribed drugs without looking at the prescription; 15.7% needed to
      read it in order to remember the drugs; 7.2% could not remember the drugs and
      said that a pharmacist had to help them and 6% could not remember or read the
      prescription. CONCLUSION: Aspects related to the poor understanding of pediatric
      prescriptions are caused by the low social, economic and cultural status of the
      adult accompanying the child; as well as aspects regarding physicians such as the
      use of symbols and abbreviations, illegible handwriting and verbal orientation
      only.

PMID- 14647797
TI  - [The influence of poor nutrition on the necessity of mechanical ventilation among
      children admitted to the Pediatric Intensive Care Unit].
AB  - OBJECTIVE: To determine the relation between children's nutritional status when
      they are admitted to the Pediatric Intensive Care Unit, the necessity and length
      of mechanical ventilation and the mortality rate. METHODS: A cohort study was
      conducted between July 1st, 1995 and June 30th, 1996. This study involved all
      children (28 days old to 48 months old) admitted to the pediatric intensive care
      unit of Hospital Sao Lucas, who stayed there longer than 8 hours. Exclusion
      criteria were complex cardiac disease, admission to the pediatric intensive care
      unit for elective procedure (regardless of pediatric intensive care unit
      admission criteria) or elective mechanical ventilation (cardiac, thoracic or
      other postoperative period). The staff responsible for the daily data collection
      were not involved with patient care or assistance decisions. On the day of
      admission to the pediatric intensive care unit, patients were evaluated regarding
      their nutritional status through the z score and the severity of the disease
      using the Pediatric Risk Mortality score. Demographic data, necessity and length
      of mechanical ventilation as well as main diagnosis and evolution of each patient
      were evaluated every day. RESULTS: Malnourishment increased significantly the
      need for mechanical ventilation, especially when associated with (a) age under
      one year old (RR=2.4; 1.4-3.8); (b) children admitted to the pediatric intensive
      care unit with low Pediatric Risk Mortality score (less than 10) (RR=2.5; 1.3
      4.7); (c) presence of respiratory disease (RR=2.1; 1.3-4.7). Otherwise,
      malnourishment did not show any influence on the mortality rate. CONCLUSION: In
      our study, we could demonstrate that malnourishment in children under 4 years old
      admitted to the pediatric intensive care unit represented a decisive factor on
      evolution, increasing significantly the necessity and the length of mechanical
      ventilation as well as the length of stay at the pediatric intensive care unit.

PMID- 14647798
TI  - [Urinary excretion of calcium, uric acid and citrate in healthy children and
      adolescents].
AB  - OBJECTIVE: To obtain regional reference values for calcium, uric acid and citrate
      urinary excretion and establish a correlation between those excretions in 24-hour
      urine sample and single urine sample for their use in clinical practice. METHODS:
      A hundred and twenty-five healthy children and adolescents were randomly chosen
      and submitted to the following protocol: clinical examination, biochemical
      analysis of blood, blood cell count, parathormone, 24-hour urine, fasting urine
      sample and stool test. RESULTS: The maximum value of calcium excretion in 24-hour
      urine was 3.75 mg/kg; in mg/dl of the glomerular filtration rate, it was 0.10;
      and for the calcium/creatinine (mg/dl) ratio in the fasting urine sample was
      0.25. Positive correlation was observed between calcium excretion in the 24-hour
      urine and the fasting sample (mg/dl and mg/dl of glomerular filtration rate). The
      maximum values of uric acid excretion in 24-hour urine were 600, 450, and 320 mg
      and 13, 15 and 18 mg/kg for adolescents, school and preschool children,
      respectively; in mg/dl of glomerular filtration rate, in the fasting urine
      sample, it was 0.47. Positive correlation was observed for the uric acid
      excretion in 24-hour urine and fasting urine samples. The mean values for the
      citrate excretion in 24-hour urine were 1.6, 1.1 and 0.5 mmol for adolescents,
      school and preschool children, respectively; for citrate/creatinine ratio, in the
      fasting urine sample the mean value was 0.3. CONCLUSIONS: The calcium and uric
      acid excretion in 24-hour urine showed correlation with those in the fasting
      urine sample, which allows their use for metabolic diagnosis, population studies
      and follow-up of patients with hypercalciuria and hyperuricosuria without voiding
      control; the citrate/creatinine ratio in the fasting urine sample can be used for
      controlling patients with hypocitraturia.

PMID- 14647799
TI  - [Results of nutritional intervention in children and adolescents with cystic
      fibrosis].
AB  - OBJECTIVE: Few studies have verified longitudinally the evolution of the
      nutritional status of patients with cystic fibrosis. The objective of this study
      is to follow the evolution of the nutritional status, body composition and energy
      consumption, macronutrients and micronutrients ingested by children and
      adolescents by means of nutritional interventions at the Clinic of Cystic
      Fibrosis/Pediatric Pneumology of the Department of Pediatrics of Universidade
      Federal de Sao Paulo. METHODS: 18 patients were involved in this study, thirteen
      males and five females with ages ranging from 0.3 to 18.4 years. We performed
      three evaluations: evaluation 1 (M1--prenutritional intervention), M2 after 6
      months, and M3 after 12 months. In these three instances we verified: the z score
      for weight/age, weight/height and height/age and the calculation of a 3-day diet
      record. We verified the body composition (anthropometry) in M1 and M3. The
      nutritional interventions were hypercaloric, hyperproteic, with adequate amount
      of ingested macronutrients and micronutrients. RESULTS: We observed an increase
      in the z score for height/age (M1=-1.07; M2=-0.69; M3=-0.50) and fat-free mass
      after the nutritional interventions, without improvement in the z score for
      weight/height and fat mass. We verified an increase in the energy intake during
      M2 (139%) and M3 (132%) compared to M1 (106%). Remarkable increase in the intake
      of protein, calcium, iron and vitamin C by the patients was found. The occurrence
      of anemia was found in 44% (8/18) of the patients. CONCLUSION: The improvement of
      the z score in height/age and fat-free mass was probably due to the increase in
      energy consumption after the nutritional intervention. A significant improvement
      in the z score for weight/height and fat mass was not found, probably due to a
      gain in height and fat-free mass.

PMID- 14647800
TI  - [Primary hyperoxaluria with endstage renal failure in an infant].
AB  - OBJECTIVE: To report a case of an infant with endstage renal failure caused by
      primary hyperoxaluria. METHODS: The review of the literature showed the rarity of
      the disease. In France, the prevalence is about 1.05/million and the incidence
      rate is 0.12/million/year. A survey, performed in international specialized
      centers in 1999, documented 78 cases in infants; in 14% of them the initial onset
      symptom was uremia. The rarity and severity of the disease justify the
      description of this case. RESULTS: A girl presenting vomiting and failure to
      thrive within the first months of life developed endstage renal failure at 6
      months of age. She was being treated with dialysis. At 8 months of age, she was
      referred for investigation. She was undernourished and the laboratory
      examinations showed urea (69 mg/dl), creatinine (2.2 mg/dl) and creatinine
      clearance (12.5 ml/min/1.73 m2 SA). The routine urinalysis was normal, the renal
      ultrasound showed increased echogenicity in both kidneys; the dosage of urinary
      oxalate was 9.2 mg/kg/day or 0.55 mmol/1.73 m2 SA; the urinary oxalate/creatinine
      ratio was 0.42. Renal biopsy showed calcium oxalate crystals throughout the renal
      parenchyma. The radiograph of long bones showed osteopathy and the ophthalmic
      examination showed flecked retinopathy. The child was treated with continuous
      ambulatory peritoneal dialysis and administration of pyridoxine was initiated.
      CONCLUSIONS: Primary hyperoxaluria should be considered as a differential
      diagnosis for endstage renal failure in infants, especially if there are no
      symptoms of other diseases.

PMID- 14647802
TI  - [The challenges and consolidation of a scientific journal]

PMID- 14647801
TI  - [Systemic mastocytosis in childhood: report of 3 cases].
AB  - OBJECTIVE: Mastocytosis comprises a group of diseases characterized by
      accumulation of mast cells on the skin, with the possibility of affecting other
      systems. Symptoms can be exclusively cutaneous, associated with symptoms of the
      organs involved or even systemic, due to the release of chemical mediators. Three
      cases of systemic mastocytosis are described, each case presenting different
      manifestations of the disorder. DESCRIPTION: The first report is about a patient
      with urticaria pigmentosa that presented persistent lesions until puberty when
      systemic manifestations initiated with lymphoreticular involvement, splenomegaly
      and bone marrow infiltration. In the second case, the child had bullous
      mastocytosis associated with gastrointestinal symptoms, whose investigation
      showed mast cell infiltration in the intestinal wall. The third patient presented
      an early and extensive cutaneous manifestation of mastocytosis, with a dramatic
      evolution to shock and posterior death. DISCUSSION: Clinical aspects, treatment
      and prognosis of such forms of the disease are discussed.

PMID- 14647803
TI  - [Pneumococcal infections: current considerations]

PMID- 14647804
TI  - [Escherichia coli subtypes EPEC, ETEC, EAEC, EHEC, EIEC, and DAEC in acute
      diarrhea]

PMID- 14647805
TI  - [Malnutrition and epilepsy]

PMID- 14647806
TI  - [Foreign body aspiration]
AB  - OBJECTIVE: To review the main publications on foreign body aspiration. SOURCES: A
      bibliographic search was carried out in Medline (1966-2000) and Lilacs (1979
      1999), in Portuguese, Spanish and English, using the keywords "aspiration,
      foreign body, children, adolescents". SYNTHESIS OF DATA: The universal
      distribution of these accidents was confirmed. This condition is predominant in
      males (51.0-73.0% of the cases) and in children aged under 3 years (65.8-85.0% of
      the accidents). By analyzing clinical history and physical examination together,
      we found a sensitivity and specificity of approximately 80% and 40%,
      respectively. The radiological examination was very useful for diagnosis, showing
      a sensitivity between 57.9% and 100%. Nuts are the most common inhaled objects,
      amounting to approximately 70% of the episodes. CONCLUSIONS: Rigid bronchoscopy
      is the procedure of choice and requires specialized professional training and
      well-equipped services. However, the preventive aspects of these accidents were
      not sufficiently emphasized in the context of this condition. This review has a
      specific section on these aspects.

PMID- 14647807
TI  - [Pneumococcal meningitis in children: clinical findings, most frequent serotypes
      and outcome].
AB  - OBJECTIVE: To determine mortality, morbidity, antimicrobial susceptibility and
      the most frequent serotypes in children admitted to hospital due to pneumococcal
      meningitis METHODS: Patients with meningitis caused by Streptococcus pneumoniae
      detected by culture in cerebrospinal fluid or blood, aged between 1 month and 15
      years old, admitted to two hospitals in the city of Sao Paulo, were included in
      the study. Susceptibility to penicillin was determined by the disk diffusion test
      using oxacillin 1 microg disk. If the inhibition area with oxacillin disk was
      less than 20mm, the strains were tested for penicillin, chloramphenicol,
      ceftriaxone, vancomycin and sulfamethoxazole /trimethoprim using the E test.
      RESULTS: We identified 55 patients, 52.5% of which were younger than 6 months.
      The prevalence of penicillin-nonsusceptible strains was 36%. All the strains were
      intermediately resistant (0.1 microg/ml < or =; MIC < or = 1.0 microg/ml) and 35%
      of the penicillin intermediate resistant strains were resistant to
      sulfamethoxazole/trimethoprim. The mortality rate was 20% and impaired
      neurological outcome was present in 40% of the children. The audiometric test
      revealed alteration in 60% of the children tested. Age less than 6 months was
      associated with poor outcome. The most frequent serotypes were 1, 5, 6B, 14, 19A
      and 23F, and 70% of the serotypes were included in the new 7-valent vaccine.
      CONCLUSIONS: These findings suggest that pneumococcal meningitis presents high
      mortality and morbidity and that the 7-valent conjugate vaccine would be
      potentially useful in preventing serious pneumococcal infections.

PMID- 14647808
TI  - [Etiology and evolution of bacterial meningitis in a pediatric center]
AB  - OBJECTIVE: To establish the prevalence of the etiological agents of bacterial
      meningitis in a reference center for the treatment of infectious diseases in the
      state of Minas Gerais. METHODS: Descriptive study including all children with
      probable diagnosis of meningitis between June/1999 and November/1999. RESULTS:
      There were 210 cases of meningitis, and 111 (52.9%) were caused by bacteria.
      Actually, 52 were probable bacterial meningitis (with liquor alterations) and 59
      were confirmed (with culture and/or antigen tests). The main agents were:
      Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. The
      initial treatment for children aged between three months and five years consisted
      of ampicillin and chloramphenicol. Later, the antibiotic was changed to
      penicillin in cases of Neisseria meningitidis and Streptococcus pneumoniae. and
      to chloramphenicol in cases of Haemophilus influenzae. Extended spectrum
      antimicrobial agents were used on clinical or laboratory basis, but resistant
      microorganisms were not found in cultures. CONCLUSIONS: The epidemiology of
      meningitis should be continuous and should consider local data in order to guide
      antimicrobial therapy. The continuous monitoring of the prevalent agents in each
      institution and their resistance is fundamental to the selection of antimicrobial
      drugs, preserving the antimicrobial agents, and causing less interference with
      individual colonization, without contributing to the increasing resistance of the
      agents responsible for meningeal infections.

PMID- 14647809
TI  - [Etiologic profile of acute diarrhea in children in Sao Paulo]
AB  - OBJECTIVE: To evaluate the etiologic profile of acute diarrhea in
      socioeconomically deprived children assisted at a regional pediatric emergency
      care service. METHODS: During two years all children with acute diarrhea assisted
      at a previously established day and week time schedule were included in the
      study. Other selective criteria were: a) age less than 5 years; b) nonuse of
      antibiotics in the previous month; and c) no travel outside the city in the
      previous month. Stool examination was used for the detection of the following
      microorganisms: a) rotavirus (immunofluorescence and
      counterimmunoelectrophoresis); b) bacteria - culture in MacConkey agar, SS agar,
      Columbia agar, bright green, serotyping, detection of toxins - INV, LT,ST,SLT I,
      SLT II, Sereny test, detection of virulence factors- EAF, eae, BFP; and c)
      protozoa (Hoffman and Faust). In the same period, a control group without
      diarrhea was also evaluated for the same fecal pathogens. RESULTS: Between March
      1994 and June 1996, 154 children with acute diarrhea (AD) and 42 control children
      (WAD), that is, without acute diarrhea, were selected. In the AD group,
      intestinal pathogens were detected in 112 (72.8%) cases, and in 9 (21.5%) cases
      in the WAD group. The association of two or more intestinal pathogens occurred in
      47 (30.5%) cases in the AD group, and in 3 (7.1%) cases in the WAD group. The
      pathogens identified in the AD cases were: Rotavirus: 32 (20.8%), bacteria: 53
      (34.4%), both: 25 (16.2%), and 2 (1.4%) with Giardia lamblia (in one case
      associated with Rotavirus and in another one associated with bacteria). In the
      WAD group, only bacteria were detected in 8 (19.1%) cases, and bacteria
      associated with Giardia lamblia in 1 (2.4%) case. Altogether, there were 105
      bacteria isolated in the AD group: 90 were Escherichia coli (EPEC 27, DAEC 24,
      ETEC 21, EAEC 18), 12 were Shigella sp, 2 were Salmonella sp, and one was
      Yersinia sp. Children with mixed infections (viral and bacterial) had increased
      incidence of severe vomiting, dehydration and hospitalization. CONCLUSIONS:
      Bacteria were the most frequent pathogens detected in acute diarrhea cases, among
      which Escherichia coli was highly predominant. The majority of Escherichia coli
      strains belong to non-EPEC varieties, strains that are not routinely evaluated in
      clinical laboratories of pathology. Rotavirus was found in a great number of
      diarrhea cases, often associated with bacteria. Protozoa showed reduced
      importance.

PMID- 14647810
TI  - [Effects of early malnutrition and nutritional rehabilitation in rats]
AB  - OBJECTIVE: To verify the effects of malnutrition and nutritional rehabilitation
      regarding seizure threshold, body weight and brain weight in rats. METHODS:
      Pregnant Wistar rats and their pups were used. Part of the rat pups were
      submitted to a malnutrition protocol and the rest served as nourished controls.
      At P15, malnourished and control rats were submitted to status epilepticus
      induced by flurothyl; and the rehabilitation period started after recovery from
      seizures. At P30, all rats were submitted to single flurothyl-induced seizures
      and the threshold was determined. After the seizures, the rats were sacrificed,
      the brain removed and weighed. Rat pups were weighed daily from age P2 to P30.
      RESULTS: Significant differences as to body weight between malnourished and
      nourished rats were observed from P5 onwards. At P30, even after nutritional
      rehabilitation, there were still differences in terms of body weight. Nourished
      (mean 1.47 g -/+ 0.17) and male (mean 1.47 g -/+ 0.16) rats had brain weight
      slightly higher than that presented by malnourished (mean 1.42 g -/+ 0.17) and
      female (mean 1.38 g -/+ 0.12) rats; however, the difference was not significant.
      Differences observed in the threshold for the first clonic and tonic seizure at
      ages P15 and P30 between the groups were not statistically significant.
      CONCLUSIONS: Our results suggest that malnutrition does not influence seizure
      threshold in rat pups submitted to flurothyl-induced seizures. Early nutritional
      rehabilitation seems to have a protective effect on seizure threshold in
      previously malnourished animals.

PMID- 14647811
TI  - [Peak expiratory flow rate in the management of cystic fibrosis]
AB  - OBJECTIVE: To verify the role of peak expiratory flow, measured through portable
      meters, as an alternative test to assess pulmonary disease in cystic fibrosis.
      METHODS: Forty-nine patients aged five to 19 years old in stable health condition
      and able to perform the peak expiratory flow maneuver were included. In the same
      visit, Shwachman-Kulczycki score was recorded. Linear regression was used to
      assess the correlation between the Shwachman-Kulczycki score and the peak
      expiratory flow rate. A P value of 0.05 was considered to be significant.
      RESULTS: A slight, but statistically significant correlation between absolute and
      percent values for this functional parameter and the Shwachman-Kulczycki score (r
      = 0.31, P = 0.02 and r = 0.30, P = 0.03, respectively) was found. CONCLUSIONS:
      Although this correlation was statistically significant, these findings are not
      clinically relevant, i.e., the lung involvement in this disease should be
      assessed by classic pulmonary function tests, such as spirometry.

PMID- 14647812
TI  - [Anemia in children under 3 years of age in public day care centers]
AB  - OBJECTIVE: To study the prevalence of anemia in children aged less than 36 months
      in public day care centers in the city of Cuiaba, state of Mato Grosso, Brazil.
      METHODS: Cross-sectional study with all children (n=271) less than 36 months of
      age who attended public day care centers in mid-1997. Children were evaluated as
      to their hemoglobin levels (venous blood, analyzed at the Central State
      Laboratory) and anthropometric indicators (weight/age, height/age,
      weight/height). RESULTS: A high prevalence (63%) of anemia associated with age,
      weight and height deficit, and time of admittance at kindergarten was observed.
      The prevalence of malnutrition was 0.8% according to the weight/height ratio,
      5.0% according to weight/age deficit, and showed an inadequacy of 10.3% as to the
      height/age ratio. Thus, the percentage of anemic children was six times higher
      than the height deficit and twelve times higher than the weight deficit.
      Malnutrition was not in fact associated with anemia, but at extreme
      anthropometric cut-off points of height and weight for age (< -2 z score), there
      is an association between these conditions. CONCLUSION: The high prevalence of
      anemia is regarded as a severe public health problem among preschool children in
      the city of Cuiaba.

PMID- 14647813
TI  - [Does drug therapy in the postpartum period interfere with breastfeeding
      recommendations?]
AB  - OBJECTIVE: To study the frequency of medication use in the immediate postpartum
      period and to evaluate possible effects on breastfeeding. METHODS: A cross
      sectional study was carried out with 2,173 women that gave birth in four
      hospitals in Belo Horizonte, a city in the southeast of Brazil, between July 1998
      and July 1999. The sample was calculated by means of the data obtained from the
      Citys Health Department according to the number of labors made in these four
      hospitals in 1995, which amounts to approximately 5% of the total number that
      usually occurs within a year. Women were randomized according to the calendar of
      epidemiological weeks. The interviews consisted of a questionnaire through which
      information about breastfeeding and sociodemographic data were obtained. In
      addition, the data were collected from mothers and newborns medical records. The
      drugs were classified according to their compatibility and incompatibility with
      breastfeeding, and were monitored as to the possible adverse effects on newborn
      infants. RESULTS: 2,090 (96.2%) of 2,173 women received drug therapy in the
      immediate postpartum period. Among the drugs used, 2,054 (98.3%) were not
      contraindicated for breastfeeding; 338 (16.2%) did not contain safe information,
      and 3 (0.14%) were contraindicated. CONCLUSIONS: Although drug therapy was
      widespread among the mothers followed up at these four hospitals, there seems to
      be no influence on breastfeeding. Fortunately, most prescribed drugs did not
      interfere with mothers and infants health.

PMID- 14647814
TI  - [Uveitis in juvenile idiopathic arthritis]
AB  - OBJECTIVE: To evaluate the frequency of chronic anterior uveitis in patients with
      juvenile idiopathic arthritis and its association with the presence of
      antinuclear antibodies. PATIENTS AND METHODS: We retrospectively studied 72
      patients with juvenile idiopathic arthritis. All of them were submitted to slit
      lamp examination of the anterior chamber at diagnosis. Both antinuclear
      antibodies and rheumatoid factor were determined. Patients with positive results
      for antinuclear antibodies were evaluated every three months and those with
      negative results were assessed every six months. RESULTS: Forty patients were
      male (55.5%) and 36 were Caucasoid (50%). The mean age at the onset of juvenile
      idiopathic arthritis was 6.4 years (range = 1 to 14 years) and the mean age at
      the beginning of the study was 10.4 years (1 to 19 years). According to the type
      of disease at onset, 32 were pauciarticular (44.4%) (17 boys and 15 girls), 30
      were polyarticular (41.6%) (17 boys and 13 girls) and 10 were systemic (14%) (6
      boys and 4 girls). We observed chronic anterior uveitis in five patients (6.5%)
      (mean age = 11.4 years). Among them, four (80%) had pauciarticular juvenile
      idiopathic arthritis at disease onset (three girls with type I juvenile
      idiopathic arthritis and positive antinuclear antibodies and one boy with type I
      juvenile idiopathic arthritis and negative antinuclear antibodies) and one girl
      with polyarticular juvenile idiopathic arthritis (negative antinuclear antibodies
      and rheumatoid factor). In this group, the mean age at the onset of juvenile
      idiopathic arthritis was 5.1 years and the mean age of uveitis onset was 9 years.
      Antinuclear antibodies were positive in 3/5 patients (60%) with uveitis.
      Antinuclear antibodies were positive in 12% of the patients without uveitis (n =
      67). Among the patients with uveitis, three had only one flare and the other two
      had four flares with cataract. The frequency of antinuclear antibodies was
      statistically higher in the patients with uveitis (P< 0.05). CONCLUSION: Although
      the incidence of uveitis in our study was lower than that reported in the
      literature, the frequency of uveitis was higher in females, in those with
      pauciarticular juvenile idiopathic arthritis and in patients with positive
      antinuclear antibodies.

PMID- 14647815
TI  - [Fiberoptic endoscopic swallowing disorders in chronic encephalopathy]
AB  - OBJECTIVE: To evaluate the results of fiberoptic endoscopic examination of
      swallowing safety in children with cerebral encephalopathy in order to identify
      patients with oropharyngeal dysphagia. METHODS: 68 children from the Association
      for the Care of Disabled Children (Associacao de Assistencia a Crianca Deficiente
      -AACD), Sao Paulo, were submitted to fiberoptic endoscopic examination of
      swallowing safety from March 1999 to March 2000. RESULTS: We observed premature
      spillage (53%), penetration in a pureed consistency (5.9%), penetration in a
      liquid consistency (4.4%), tracheal aspiration in a pureed consistency (14.7%),
      tracheal aspiration in a liquid consistency (32.3%), residue (7.4%), cough
      effectiveness (44.1%). CONCLUSIONS: Children showed a high incidence of
      pharyngeal swallowing disorders. Tracheal aspiration was the most important
      disorder because it is related with high morbidity in children with cerebral
      encephalopathy. The texture and consistency of the patientacute;s diet may be
      modified to decrease the risk of aspiration and improve swallowing examination.

PMID- 14647816
TI  - [Sensorineural hearing loss associated to Kawasaki Disease]
AB  - OBJECTIVE: Kawasaki disease is a systemic idiopathic self-limited vasculitis of
      small and medium-sized vessels. Thirteen cases of sensorineural hearing loss
      during the evolution of this disease have been described in the literature. We
      describe a case of an infant with Kawasaki disease who developed sensorineural
      hearing loss during the acute phase. This case report shows a complication of
      Kawasaki disease, with few citations in literature, enhancing the importance of
      careful evaluation of these patients. DESCRIPTION: Nineteen-month-old-boy,
      formerly healthy, with persistent daily fever seven days before admission,
      associated with irritability, bilateral nonexudative conjunctivitis and
      maculopapular erythema on his trunk. There was later development of arthritis on
      wrists, elbows, knees, and ankles, and swelling associated with desquamation of
      hands and feet, which prevented him from walking. The diagnosis of Kawasaki
      disease was established according to the American Heart Associations criteria,
      and the child was conventionally treated. There was regression of clinical
      manifestations three days after the beginning of treatment. However, one month
      after the onset of symptoms, the family noticed an unsatisfactory response to
      sound stimuli. The evaluation of auditory acuity through BERA (Brainstem Evoked
      Responses Audiometry) revealed severe bilateral sensorineural hearing loss.
      COMMENTS: Routine examination of auditory acuity in children with Kawasaki
      disease may help identify sensorineural hearing loss at an early stage.

PMID- 14647817
TI  - [Essential primary cutis verticis gyrata]
AB  - OBJECTIVE: To report a rare case of a child with essential primary Cutis verticis
      gyrata. REPORT: Nine-year-old boy with extensive hypertrophy of scalp skin, with
      a cerebriform appearance. No underlying neurologic and ophthalmologic disorders
      were found, and no other cases were described in his family. COMMENTS: The
      diagnosis of primary Cutis verticis gyrata was established by thickening of the
      scalp and absence of neurologic and ophthalmologic abnormalities. Differential
      diagnosis comprises secondary conditions such as: cerebriform intradermal nevus,
      pachydermoperiostosis, acromegaly, and inflammatory diseases of the scalp. This
      is the first report of a child with this form of Cutis verticis gyrata.

PMID- 14647819
TI  - [Prognostic indicators in neonatology]

PMID- 14647818
TI  - [Risk or protective factors?]

PMID- 14647820
TI  - [New approaches to postneonatal mortality]

PMID- 14647821
TI  - [Experimental empyema in rats through intrapleural injection of bacteria]

PMID- 14647822
TI  - [Immunity related to allergic response at the beginning of life]
AB  - OBJECTIVE: Given that the most common allergic manifestations (asthma, rhinitis,
      dermatitis, food allergies) occur during childhood, because the immune system can
      be induced into sensitization rather than into allergenic tolerance at the
      beginning of life, we analyzed the main immunological aspects of fetuses and
      infant in terms of allergic sensitization and response. METHODS: Detailed
      bibliographic revision concerning nonspecific immune response (physical and
      chemical barriers, myeloid cells) and specific immune response (T and B
      lymphocytes, cytokines) of the fetus and infant, with special attention to
      studies carried out in the last fifteen years. RESULTS: Various compartments of
      the immune system in fetuses and infants are different from those present in
      older children and adults. Thus, developmental aspects of nonspecific and
      specific immunity may contribute to atopic disease. CONCLUSIONS: Atopic
      predisposition is determined at the beginning of life and seems to originate not
      only from genetic factors, but also from intrauterine environment and initial
      stage of childhood, inducing the immune system to increase the synthesis of IgE.

PMID- 14647823
TI  - [Risk factors, clinical and laboratory aspects of asthma in children]
AB  - OBJECTIVE: To evaluate the clinical and laboratory aspects and the risk factors
      associated with asthma in children treated at the Pediatric Outpatient Clinic of
      Hospital Universitario Julio Muller. METHODS: A case-control study including 59
      asthmatic children (cases) and 104 nonasthmatic children (controls). The
      following factors were considered for risk analysis: parents level of education,
      domestic exposure to allergens, passive smoking, breast feeding, low income, and
      family history of allergy. Samples of blood were collected for hemogram and to
      determine the total serum IgE as well as the one specific to allergens. Immediate
      hypersensitivity skin tests were performed with puncture for the detection of the
      following allergens: house dust mite, animals, molds, and cockroaches with
      positive (histamine) and negative controls (physiologic solution). A logistic
      regression model was used to calculate the odds ratio (OR) and 95% confidence
      intervals (95%CI) adjusted for risk factors and for confounding factors. RESULTS:
      Among the risk factors studied, sex, parents low level of education, low income,
      length of the breast feeding period, and passive smoking were not associated with
      the presence of asthma. The domestic exposure to allergens was similar in both
      groups except for the higher frequency of pets at the homes of control patients
      (chi-square=16.9; P<0.05). Paternal history of rhinitis was the only association
      with asthma (OR=3.33; 95%CI: 1.03-11.17; P<0.05). The asthmatic children
      presented higher frequency of positive reactions to skin tests than the controls,
      mainly to house dust mites: Dermatophagoides pteronyssinus (69.5%),
      Dermatophagoides farinae (59.3%) and Blomia tropicalis (59.3%); cockroaches:
      Periplaneta americana (59.3%), and cat: Felis domesticus (37.3%), with OR between
      11.2-21.0; P<0.05. Eosinophilia and serum levels of total IgE were more elevated
      in the group of asthmatic children (P<0.05). The positivity of the specific IgE
      test for Dermatophagoides pteronyssinus and Blomia tropicalis was higher in the
      cases than in the controls (P<0.05). The multivariate analysis showed that
      sensitization to the allergens produced by cockroaches (OR=9.26; 95%CI: 2.59
      33.4), animals (OR=3.93; 95%CI: 1.05-14.67) and house dust mites (OR=3.74; 95%CI:
      1.18-11.8) were the most important risk factors for asthma. CONCLUSIONS: The
      sensitization to indoor allergens, mainly to house dust mites, cockroaches, and
      cats showed a strong association with asthma in this study.

PMID- 14647824
TI  - [Predictive value of SNAP and SNAP-PE for neonatal mortality]
AB  - OBJECTIVE: To evaluate the Score for Neonatal Acute Physiology and the Score for
      Neonatal Acute Physiology Perinatal Extension as neonatal mortality predictors in
      our neonatal intensive care unit, and to compare their results. METHODS: All
      newborn infants admitted to our neonatal intensive care unit from March 1997
      through December 1998 were prospectively evaluated just at completion of 24 hours
      of life for SNAP and SNAP-PE. Exclusion criteria were: death or discharge from
      the neonatal intensive care unit in the first 24 hours of life, congenital
      malformations incompatible with life, and outborn infants. RESULTS: 553 newborn
      infants were included in the study and 54 died. The median SNAP and SNAP-PE
      values were higher in those who died. Infants were allocated to five different
      raising ranges of SNAP and SNAP-PE severity. SNAP: up to 6, 7-11, 12-15, 16-24,
      higher than 24 (mortality: 3%, 11%, 29%, 48%,75%, respectively). SNAP-PE: up to
      11, 12-23, 24-32, 33-50, higher than 50 (mortality: 3%, 10%, 53%, 78%, 83%,
      respectively). The optimal cut off points based on ROC curve were 12 for SNAP,
      and 24 for SNAP-PE. Sensitivity, specificity, positive predictive value (PPV),
      and negative predictive value (NPV) for death were figured out. SNAP 12:
      sensitivity 79.6%, specificity 71.7%, PPV 23.4%, NPV 97%. SNAP-PE 24: sensitivity
      79.6%, specificity 80%, PPV 30%, NPV 97.3%. The area under the curve (Az) were
      81.4% for SNAP, and 85.1% for SNAP-PE, both statistically significant. There were
      no statistical differences between the two areas under the curve. CONCLUSIONS:
      SNAP and SNAP-PE are excellent predictors of neonatal survival. Therefore, we
      recommend their use in Neonatal Intensive Care Units.

PMID- 14647825
TI  - [Postneonatal infant mortality and quality of medical care: a case-control study]
AB  - OBJECTIVE: To identify the risk factors for postneonatal infant mortality caused
      by diarrhea and pneumonia in relation to the quality of medical assistance.
      METHODS: Population-based case-control study of 277 postneonatal infant deaths
      caused by diarrhea and pneumonia occurring in the metropolitan area of Belo
      Horizonte, Brazil, between May/1991 and April/1992. The cases were compared with
      hospitalized controls, and matched by pathology, age and hospital. Information on
      cases and controls were collected from medical records and through home
      interviews. Some variables related to the quality of medical care were analyzed.
      McNemar test and conditional logistic regression were used to define the risk
      factors for postneonatal deaths. RESULTS: Multiple logistic regression analysis
      showed the following factors independently associated with increased risk of
      postneonatal death induced by diarrhea and pneumonia: delayed immunization (OR =
      2.48; 95%CI=1.17-5.23), general status (serious) on hospital admission (OR=10.94;
      95%CI=4.91-24.34), unaccomplished hospital procedures (OR=10.08; 95%CI = 3.55
      20.59) and malnutrition on hospital admission (OR=3.58; 95%CI=1.42-9.07).
      CONCLUSIONS: The results indicate the low quality of medical assistance as an
      important risk factor for avoidable causes of postneonatal deaths. The authors
      highlight the lack of integration between the outpatient clinic and hospital
      activities as an important determinant of low quality. It is necessary that the
      performance of health services and their effect on avoidable infant mortality be
      widely discussed, also taking into consideration the preponderant role of
      socioeconomic variables

PMID- 14647826
TI  - [Experimental empyema in rats through intrapleural injection of bacteria]
AB  - OBJECTIVE: To evaluate empyema formation in rats through the injection of two
      bacteria (Pasteurella multocida and Staphylococcus aureus), using a simple, easy
      to-use surgical technique. METHODS: Twenty four anesthetized Wistar white rats,
      250-300g in weight, submitted to right anterior thoracotomy, muscular retraction
      and injection of a 0.2ml solution into pleural space according the following
      scheme: Group I (n=12): injection of 10(10) Pasteurella multocida cultured in
      brain heart infusion broth. Group II (n=8): injection of 10(10) Staphylococcus
      aureus cultured in brain heart infusion broth. Group III (n=4): injection of
      bacterium-free brain heart infusion (control). The rats were sacrificed after
      seven days, and pleural reaction was assessed by macroscopy. Mortality, and
      intrathoracic liquid volume were evaluated, and bacteriological tests were also
      performed. RESULTS: Seven rats died within the first 48 hours in Group I
      (Pasteurella multocida); five completed the experiment, but none of them
      presented empyema. Only one animal died within the first 24 hours in Group II
      (Staphylococcus aureus); seven (88%) presented empyema at the time of sacrifice.
      All animals survived in Group III (control), without empyema or thoracic
      abnormalities. Pleural inoculation of Staphylococcus aureus (Group II) was
      significantly associated with empyema formation (P<0.001). In this group, the
      amount of pleural liquid ranged from 0.9 to 3.9ml. CONCLUSION: It is possible to
      induce empyema in rats through Staphylococcus aureus pleural injection by a
      simple surgical technique. Differently from other experiments, the pleural
      injection of Pasteurella multocida did not provoke empyema in rats.

PMID- 14647827
TI  - [Cerebral CT scan alterations in children with ocular lesions caused by
      congenital toxoplasmosis]
AB  - OBJECTIVE: To evaluate the frequency and the types of cerebral CT scan
      alterations in patients with ocular lesions caused by congenital toxoplasmosis.
      METHODS: The patients should fit one of the following criteria: reagent IgM
      serology for toxoplasmosis at birth and mother with positive serology for
      toxoplasmosis; age less than ten years, with bilateral funduscopic lesions
      compatible with toxoplasmic retinochoroiditis; or reagent IgG serology for
      toxoplasmosis and mother with positive serology for toxoplasmosis. All patients
      were submitted to noncontrast cerebral CT scan. RESULTS: Twenty-two patients
      participated in this study (44 eyes). Thirteen eyes presented macular lesions
      (29.5%), eight had peripheral lesions (18.2%) and 22 eyes had concomitant macular
      and peripheral lesions (50%). Seventeen patients presented radiological
      alterations (77.3%). Among these, sixteen patients (94.1%) presented brain
      calcifications, two patients (11.7%) presented ventricular dilation, two patients
      (11.7%) had hydrocephalus, one had hydranencephaly (5.9%), one presented
      porencephalic cyst (cerebral hemiatrophy) (5.9%), one had arachnoid cyst (5.9%)
      and one had mild dilation of ventricles and subarachnoid cistern (5.9%).
      CONCLUSIONS: Patients diagnosed with congenital toxoplasmosis and ocular lesions
      should be investigated for concomitant neuroradiologic alterations.

PMID- 14647828
TI  - [Evaluation of mothers knowledge about oral rehydration therapy and sodium
      concentration in homemade sugar salt solutions]
AB  - OBJECTIVE: To evaluate mothers knowledge about oral rehydration therapy and to
      determine the concentration of sodium in sugar salt solutions prepared by the
      interviewed mothers. METHODS: Cross-sectional study of low-income families from
      the suburbs of Natal, a city in the state of Rio Grande do Norte. One hundred and
      thirty six households with children younger than 5 years were visited. The
      information on when to use the solution, how to administrate it and how to
      prepare it was provided by the interviewed mothers. The concentration of sodium
      was determined in 100 solutions prepared by those mothers. RESULTS: Only 9.0% of
      mothers had appropriate knowledge about when to use the solution and 21.0% knew
      how to administer it correctly. The error rates regarding the measurement of
      ingredients were: 2.5% for salt, 22.2% for water and 43.2% for sugar, according
      to the answers given by 81 mothers, who used a double-ended spoon made of plastic
      to measure quantities. In fifty percent of the analyzed samples, sodium was
      within safe limits (30 mmol/l to 100 mmol/l). Those considered dangerous (>100
      mmol/l) or inefficient solutions (<30 mmol/l) reached the percentage of 47.0% and
      3.0%, respectively. Out of the 69 solutions prepared with the double-ended spoon,
      63.8% were found appropriate in terms of sodium concentration, while only 19.3%
      of the 31 solutions prepared using other measuring utensils were within
      acceptable limits (P=0.0001). CONCLUSION: Mothers knowledge about oral
      rehydration therapy was considered poor. Moreover, the concentration of sodium in
      sugar salt solutions seldom remains within safe limits, particularly those
      solutions in which the double-ended spoon was not used for preparation. These
      conclusions should be considered in future educational programs on oral
      rehydration.

PMID- 14647829
TI  - [Maternal conceptions of infantile diarrhea]
AB  - OBJECTIVE: To understand maternal conceptions of infantile diarrhea, encouraging
      reflection on the importance of communication between mothers and health
      services. METHODS: Survey carried out in selected areas of six towns in the state
      of Pernambuco, all of which participated in the diarrhea control project
      coordinated by the State Health Secretariat. The information was obtained through
      interviews with 770 mothers, producing a representative sample of 1,026 children
      younger than five years. RESULTS: In general, mothers associated the occurrence
      of diarrhea with some kinds of food (fatty or undercooked). Better educated
      mothers, regardless of their place of residence, attributed it to improper
      hygiene and sanitation, whereas illiterate and poorly educated mothers, from the
      metropolitan region of Recife, blamed it on hot weather, and those living in the
      countryside believe the occurrence of diarrhea is related to teething. Circa
      24.2% (63.4% living in the countryside) do not know how to prevent the disease.
      The two preventive measures most frequently adopted consist in drinking treated
      water and cooking food thoroughly. Only 0.5% mentioned breast-feeding. The number
      of children still alive and their ages influence maternal conceptions. The main
      sources of information about the prevention of diarrhea are the support network
      (45.5%), the health sector (35.9%) and the media (33.2%). CONCLUSIONS: The
      insufficient participation of the health sector in the information network about
      diarrhea, misinformation, and sharp disagreement over maternal conceptions and
      technical knowledge, which are the cornerstone of institutional measures, show
      that it is necessary to value the communicative dimension of the educational
      approach in child care.

PMID- 14647830
TI  - [Search of antimeasles antibodies in HIV-infected children after basic
      immunization]
AB  - OBJECTIVE: To determine the presence of antimeasles antibodies in children
      perinatally infected with HIV and properly immunized. METHODS: A retrospective
      cohort study conducted in Belo Horizonte by the Universidade Federal de Minas
      Gerais, between 1995 and 1996. Twenty one children perinatally infected with HIV
      and 29 immunocompetent noninfected children were included in the study.
      Information about measles vaccination was obtained from patients immunization
      charts. The presence of neutralizing antibodies against the measles was
      determined by the plaque reduction neutralization test and IgM was measured by
      ELISA. The level of significance was set at 5% in all the performed statistical
      analyses. RESULTS: Median age was 44.5 months for HIV-infected patients and 62.0
      months for noninfected children (P=0.64). Both groups received on average two
      doses of antimeasles vaccine. All HIV-seronegative patients presented antimeasles
      antibody titers greater than 50 mIU/ml, whereas 57.1% of infected children
      presented titers above this value (P=0.0001). The geometric mean titer of
      neutralizing antibodies was significantly lower in the group of HIV-infected
      children (433.5 mIU/ml) than in noninfected children (1,668.1 mIU/ml), P=0.001.
      All patients in both groups were negative for antimeasles IgM. CONCLUSION: In the
      present study, HIV-infected children showed a lower seroprevalence of antimeasles
      antibody after immunization than noninfected children. These results emphasize
      the risk of acquisition of measles virus and the need to evaluate alternatives to
      the vaccination of HIV-infected children in an attempt to maximize the protection
      against the measles in this group of patients.

PMID- 14647831
TI  - [Clinical aspects and complete blood counts in children exposed to HIV-1:
      comparison between infected patients and seroreverters]
AB  - OBJECTIVE: To analyze the evolution of clinical and hematological aspects of
      children exposed to the vertical transmission of HIV-1, comparing infected
      patients with uninfected ones or seroreverters. METHODS: Prospective,
      descriptive, longitudinal study. We analyzed 79 children born from HIV-1 infected
      mothers, under clinical follow up from March, 1996 until November, 1997, at the
      Immunodeficiency division of the Hospital de Clinicas da Unicamp (State
      University Hospital of Campinas). RESULTS: Failure to thrive was observed in both
      groups, but was greater among seroreverters. Among the infected children, 23
      mothers did not use AZT during pregnancy, 16 of them (61.5%) had been breastfed,
      four were classified into clinical category N, seven into A and fifteen into B.
      Clinical manifestations in patients younger than one year were seen in 18
      infected children (69.2%). Anemia was observed in 73.1% of the infected group and
      in 41.5% of the seroreverters (P<0.008). The comparison between the groups showed
      that the most common hematologic alterations in the infected children was
      microcytosis and hypochromia (P<0.05), lymphopenia between 15 and 18 months
      (P<0.05), monocytosis between 9 and 12 months (P<0.05) and a tendency towards
      high ferritin levels, with no statistical significance. CONCLUSIONS: Microcytic
      and hypochromic anemia were observed in both groups: iron deficiency in the
      uninfected children, and chronic disease anemia in the infected ones. The
      infected children presented with monocytosis and lymphopenia at an earlier stage.

PMID- 14647832
TI  - [Nutrient and energy intake in adolescents from a public school]
AB  - OBJECTIVE: To assess the average intake of energy, protein, calcium, iron,
      vitamins A and C in adolescents. METHODS: Cross-sectional study in a high school
      in Sao Paulo, Brazil, with 92 students, both males and females, aged between 11
      and 17. The sample was chosen by a systematic statistical selection. The food
      intake was determined by 24-h diet recall and compared with the National Research
      Council recommendation (1989). RESULTS: The average intake of energy, proteins
      and vitamin C by both males and females was higher than the recommendation. The
      average iron intake by males was higher than the recommendation and more than 80%
      in females. The average calcium intake by males was less than 70% and less than
      50% in females. CONCLUSIONS: Low average intake of calcium and high average
      intake of energy were observed.

PMID- 14647833
TI  - [Renal arterial thrombosis and the antiphospholipid antibody syndrome: a case
      report]
AB  - OBJECTIVE: To describe an unusual case with clinical features of the
      antiphospholipid syndrome. DESCRIPTION: White child, two years and six months
      old, with renal failure, renal arterial thrombosis, and diagnosis of
      antiphospholipid syndrome was hospitalized with a history of abdominal pain,
      pallor, lethargy, and anuria for 36 hours. On physical examination, the patient
      showed malnutrition, high blood pressure, moderate edema, and hypochondrial pain.
      Laboratory findings included: urea=112mg/dl, serum creatinine= 4.5 mg/dl, blood
      pH= 7.47, blood bicarbonate= 12.8 mmol/L, K=7.2 mEq/L. Peritoneal dialysis was
      started and maintained for 11 days. After 7 weeks, the patient still needed anti
      hypertensive drugs and the renal function was still abnormal. Renal biopsy was
      performed and revealed renal infarction. The result of Doppler ultrasonography
      revealed absent renal blood flow on the right side. Renal arteriography showed
      total occlusion of the right renal artery. Results for collagen diseases were
      negative. A right nephrectomy was performed and the blood pressure was
      controlled. The child was hospitalized again at 5 years and 8 months old with
      episodes of absence seizures and abdominal and precordial pain. Anticardiolipin
      antibody test was positive. The child is now 7 years old, asymptomatic, with
      negative anticardiolipin antibody, and has been under regular follow-up.
      COMMENTS: Children with arterial thrombosis should be investigated for a possible
      association with the antiphospholipid antibody syndrome even in the absence of
      collagen disease.

PMID- 14647834
TI  - [Devic disease: a case report]
AB  - OBJECTIVE: To report a case of Devic disease, emphasizing its diagnosis, in
      addition to reviewing the medical literature. DESCRIPTION: Male, six-year-old
      patient suddenly developed weakness in lower limbs, with resolution during
      hospital stay. However, as the weakness disappeared, loss of vision occurred. The
      symptoms were reverted after the use of prednisone. COMMENTS: The diagnostic and
      therapeutic approach was similar to that used in other cases reported by
      different reference centers. In other words, clinical diagnosis and prednisone
      therapy were used, with the complete improvement of symptoms. However, there is
      still some controversy surrounding its etiology and relationship with other
      demyelinating diseases, such as multiple sclerosis.

PMID- 14647835
TI  - [Bone marrow transplant in children: where are we now?]

PMID- 14647836
TI  - [Short-term effects of prone positioning on oxygenation of pediatric patients
      submitted to mechanical ventilation]

PMID- 14647837
TI  - [Fetal cocaine exposure]

PMID- 14647838
TI  - [Bone marrow transplantation and cord blood transplantation in children]
AB  - OBJECTIVE: To review the indications, main steps and complications of bone marrow
      transplantation in children. SOURCES: Medline-based literature review. SUMMARY OF
      THE FINDINGS: We comment about the indications of autologous, allogeneic and
      syngeneic bone marrow transplantation, donor selections, harvest and infusion of
      the hematopoietic progenitor cells that will reconstitute the hematopoietic and
      immune systems. We describe the different conditioning regimens and the new
      sources of cells, such as cord blood. We also describe the most common events
      after the procedure, including infections, graft versus host disease, and
      cardiovascular, pulmonary, hepatic, genitourinary, and gastrointestinal
      complications. The late effects and their impact on quality of life are also
      discussed. CONCLUSIONS: Bone marrow transplantation does not confer an absolutely
      normal life span to all the patients; however, it represents the only chance of
      cure for children with certain neoplastic or immunological diseases. By knowing
      the steps of the procedure, pediatricians can be a source of information on bone
      marrow transplantation to the patients and their families.

PMID- 14647839
TI  - [Short-term effects of prone positioning on the oxygenation of pediatric patients
      submitted to mechanical ventilation]
AB  - OBJECTIVE: To analyze the short-term effects of prone positioning on the
      oxygenation of mechanically-ventilated children suffering from severe hypoxemia.
      MATERIALS AND METHODS: A prospective, nonrandomized trial (each patient as
      his/her own control) was conducted between July 1998 and July 1999. Mechanically
      ventilated children with peak inspiratory pressure greater than or equal to 30 cm
      H(2)O, FiO(2) greater than or equal to 0.5, and PaO(2)/FiO(2) ratio less than or
      equal to 200 were included in the study. Each patient was kept in the prone
      position for two hours, returning to the supine position after this period.
      Oxygenation was assessed by means of PaO(2)/FiO(2) in the supine position (one
      hour before prone positioning), one hour after prone positioning, and one hour
      after returning to the supine position. Patients who presented an increase of at
      least 20 in PaO(2)/FiO(2) were considered responsive. The results were compared
      by Student t-test, Friedman test, chi-square test, Fishers exact test, and
      confidence interval. RESULTS: Eighteen children (10 males), whose mean age was
      11.5 -/+11.5 months, with initial PaO(2)/FiO(2) of 96.06 -/+ 41.78, participated
      in the study. After one hour in the prone position, 27.7% of the patients (5/18)
      improved their PaO(2)/FiO(2) ratio (P=0.045). Six of these patients presented
      reduced lung compliance (four of them had acute respiratory distress syndrome);
      and twelve patients showed increased airway resistance (six of them presented
      bronchiolitis). No significant difference was observed between these two groups
      (reduced lung compliance x increased airway resistance) in terms of age, sex,
      duration of ventilation prior to change in position, peak inspiratory pressure,
      FiO(2), severity of hypoxemia, and outcome. CONCLUSION: Prone positioning during
      mechanical ventilation of children with severe hypoxemia may improve the
      PaO(2)/FiO(2) ratio in the first hour.

PMID- 14647840
TI  - [Prevalence of prenatal exposure to cocaine in a sample of newborns from a
      university teaching hospital]
AB  - OBJECTIVE: To assess the prevalence of prenatal exposure to cocaine in a sample
      of newborns using two methods: fluorescence polarization immunoassay and
      interview with the mother. METHODS: This cross-sectional study was carried out in
      a university teaching hospital. The population included all live births between
      March 23, 1999 and June 01, 1999 (n=847). Exposure was determined by a
      benzoylecgonine-positive meconium specimen and/or by a positive interview with
      the mother. RESULTS: The prevalence of prenatal exposure to cocaine in this
      sample was 2.4% (16 cases) according to the interviews, and 3.4% (25 cases)
      according to the meconium analysis. A rate of 4.6% (34 cases) was found when both
      methods were associated. CONCLUSIONS: We observed that the meconium test was more
      effective than the maternal interview for the diagnosis of prenatal exposure to
      cocaine. The meconium analysis enhanced diagnostic chances by 53.4%, compared to
      26% in the case of maternal interview.

PMID- 14647841
TI  - [Do newborn infants feel pain when submitted to gastric suctioning?]
AB  - OBJECTIVES: Evaluate physiological and behavioral parameters to verify if
      newborns feel pain when submitted to gastric suctioning. METHODS: 50 healthy
      newborns over 33 weeks gestational age, weighing more than 1999g, were submitted
      to gastric suctioning, randomly selected, and divided into two groups:
      Friction/Lancing and Lancing/Friction. The newborns were assessed through the
      Neonatal Infant Pain Scale (NIPS) (0-7, pain>3) by two independent observers in
      three different moments: one minute before, during, and one minute after gastric
      suctioning, heel lancing and foot friction, with simultaneous monitoring of heart
      rate, respiratory frequency, and hemoglobin oxygen saturation. RESULTS: The
      respiratory frequency only decreased during gastric suctioning (P=0.004). The
      heart rate was lower during gastric suctioning (P<0.0001), during the heel lacing
      procedure in the Friction/Lancing group (P=0.01), and during friction in the
      Friction/Lancing group (P=0.022). The hemoglobin oxygen saturation suffered no
      alterations during the three procedures. The results obtained through NIPS
      revealed that both groups felt pain during gastric suctioning and heel lancing,
      and did not feel pain during friction (P<0.0001). CONCLUSION: During the gastric
      suctioning procedure, newborns responded as if it were a painful stimulus.
      Physiological alterations were neither specific nor sensitive to pain assessment
      in newborn infants.

PMID- 14647842
TI  - [Differences between the nutritional status of children in public preschools and
      nutritional transition]
AB  - OBJECTIVE: To verify if there are different patterns of nutritional status among
      preschool children, and if these patterns deserve special interventions. METHODS:
      This cross-sectional study included 1,200 children from public preschools in
      Cosmopolis, a small town in the state of Sao Paulo. The z scores indices for
      height/age, weight/age, and weight/height were analyzed in terms of age, sex,
      type of school, and school location. RESULTS: Anthropometric indices were similar
      to those of the reference population (NCHS). Males had lower indices than
      females. Important differences in anthropometric indices were found among
      children from different schools. Higher prevalence of moderate deficits in height
      and weight was observed in children from non-downtown areas, while higher
      prevalence of obesity was found in children from downtown areas. However, the
      prevalence of obesity was higher than the prevalence of malnutrition even in
      schools located in non-downtown areas. CONCLUSIONS: We concluded that even in a
      small city and in a relatively homogeneous group, it is possible to detect
      different nutritional patterns in subgroups of the population. The differences
      related to nutritional status, and the high prevalence of obesity among children
      from public schools, point out the need for different approaches and
      interventions.

PMID- 14647843
TI  - [Haemophilus influenzae type b meningitis in the state of Parana, Brazil]
AB  - OBJECTIVE: During the second half of 1996, the municipalities of Londrina and
      Curitiba (State of Parana, Brazil) included Haemophilus influenzae type b (Hib)
      vaccine into their routine vaccination regimen, approximately 30 months before
      its introduction into the National Immunization Program. The present study aimed
      at verifying the incidence of meningitis caused by Hib among children in
      Londrina, Curitiba, and in the remaining municipalities of the State, before and
      after the introduction of this vaccine into the immunization program. METHODS: An
      observational and retrospective study was carried out. The study included all
      cases of Haemophilus influenzae type b meningitis recorded by the epidemiological
      surveillance system in Londrina and by the State of Parana Health Secretariat
      between 1992 and 1999 among children aged less than 5 years. The incidence rates
      of Hib meningitis were calculated per 100,000 children aged less than five years.
      RESULTS: After the introduction of Hib vaccine, an important reduction in the
      incidence rate of Haemophilus influenzae type b meningitis was observed in
      Londrina (from 23.91 in 1996 to 2.79 in 1999). A Similar decrease was observed in
      Curitiba. In the remaining localities of the state, which had not introduced the
      vaccine till mid-1999, the incidence rate remained almost unchanged. CONCLUSION:
      Regular vaccination against Hib was effective in reducing the incidence rate of
      meningitis amongst children younger than five years in Londrina and Curitiba. In
      order to maintain this low incidence rate, adequate vaccination coverage and
      strict epidemiological surveillance should be guaranteed.

PMID- 14647844
TI  - [Effects of cisapride and chest physical therapy on the gastroesophageal reflux
      of wheezing babies based on scintigraphy]
AB  - OBJECTIVE: To evaluate the effect of cisapride and chest physical therapy on the
      gastroesophageal reflux of wheezing babies. METHODS: We prospectively assessed
      the presence of technetium ((99)Tc) in the upper, middle, and lower esophagus of
      25 wheezing babies (13 with GERD and 12 without GERD) using scintigraphy. Both
      groups underwent clinical investigation, including laboratory, X-ray and
      scintigraphy tests, for the etiology of the wheezing baby syndrome (WBS) and
      GERD. Expiratory Flow Acceleration (EFA) was performed before and after treatment
      with cisapride. The total time of GER episodes was accounted for each portion of
      the esophagus during scintigraphy and during EFA. RESULTS: Cisapride
      significantly reduced the total reflux time in the upper esophagus (P<0.05), but
      showed no influence during EFA. After cisapride therapy, EFA increased the total
      reflux time in the upper and medium esophagus; however, no statistical
      significance was found. Infants with GERD presented a shorter total reflux time
      in the distal esophagus (P<0.05) during EFA. After cisapride treatment, no
      statistical significance was found. Infants without GERD also presented reduced
      total reflux time in the distal esophagus during EFA (P<0.05). Those with GERD
      had increased total reflux time in the distal esophagus (P<0.05) before and after
      cisapride treatment during EFA and scintigraphy. CONCLUSIONS: Cisapride was
      effective in reducing the total reflux time, mainly in the upper esophagus. EFA
      apparently increased the number of episodes of GER, without achieving statistical
      significance. Further studies are necessary to investigate the effects of chest
      physical therapy according to body positions.

PMID- 14647845
TI  - [Organic aciduria: diagnosis in high-risk Brazilian patients]
AB  - OBJECTIVE: To determine the prevalence of organic acidurias in high-risk
      Brazilian patients. METHODS: Laboratory techniques for the detection and
      quantification of organic acids by gas chromatography/mass spectrometry were
      implemented in Porto Alegre, Brazil. We investigated 1,480 patients suspected of
      organic aciduria between January 1994 and June 2000. RESULTS: Seventy three
      (4.9%) cases of organic acidemias (acidurias) were diagnosed among the tested
      individuals. In most of these patients, prompt therapy resulted in rapid symptom
      improvement; these results are completely different from our previous cases
      diagnosed in other laboratories in Europe and the United States, where several
      patients died before any measures could be taken. CONCLUSIONS: These results
      demonstrate the importance of diagnosing organic acidurias in loco even in
      developing countries, in spite of the extra costs involved.

PMID- 14647846
TI  - [Applications of videolaparoscopic surgery in children]
AB  - OBJECTIVES: To present the videolaparoscopies performed by the Childrens Surgery
      Service, and study the main indications for pediatric laparoscopic surgeries,
      considering advantages and disadvantages over conventional open procedures.
      METHODS: Retrospective analysis of 612 videolaparoscopies in children aged
      between 8 days and 17 years treated from November/95 to 2000. Basic principles of
      videolaparoscopy and the postoperative management of several pediatric diseases
      are described. The results, advantages, and complications were analyzed after a 5
      year follow-up period. RESULTS: Laparoscopic surgery allowed for a wide series of
      abdominal procedures conventionally carried out through open surgery, mainly for
      the treatment of gastroesophageal reflux disease, inflammatory acute abdomen,
      adhesive intestinal obstruction, biliary lithiasis, tumors, cryptorchidism,
      ovarian diseases, splenectomies, aganglionosis, trauma and others. Morbidity was
      low (1%), and mortality due to laparoscopy was nonexistent. Conversion to
      laparotomy occurred in only 14 cases (2.3%), mainly because of trauma. The
      principal advantages included minimal surgical trauma, pain and reflex ileum,
      short hospital stay, almost no incisional hernias and better cosmetic scars.
      CONCLUSIONS: Videolaparoscopy seems to be a great advance in modern pediatric
      surgery, allowing safer and less invasive treatment of a wide series of abdominal
      diseases at all pediatric ages.

PMID- 14647847
TI  - [Study of mechanisms and factors related to sexual abuse in female children and
      adolescents]
AB  - OBJECTIVE: To study the frequency of sexual abuse in children and adolescents and
      its related factors. METHODS: Retrospective analysis of 617 cases of sexual
      abuse, assisted between July 1994 and August 1999 at the Womens Health Reference
      Center, divided into two groups: 71 children (age <10 years), and 546 adolescents
      (age > or =10 and <20 years). The analyzed variables were: sexual crime;
      embarrassment; presumption of violence; characteristics and number of abusers;
      the victimacute;s situation at the moment of the crime; and occurrence of
      physical traumas. Epi Info 6 software was utilized to gather data, and the
      results were analyzed by the chi-square test. RESULTS: Significant statistic
      results were found. 90.8% of the adolescents were victims of rape, and 46.5% of
      the children suffered sexual assault. The presupposed violence (PV) was more
      frequent in the group of children (63.4%) and a serious threat in the group of
      adolescents (63.2%). Innocentia consilli was exclusive PV among 100% of children
      and 59.5% of adolescents. 84.5% of children were molested by identifiable
      abusers, most frequently family members. Perpetrators were unknown in 72.3% of
      the cases of adolescent abuse. 42.3% of sexual abuse of children occurred in
      their homes, and 28.2% at the abusers. Adolescents were approached during daily
      activities (34.8%) and on their way to work or school (28.4%). Most patients did
      not have genital or extragenital trauma. CONCLUSIONS: Children suffered sexual
      assault, perpetrated by a known abuser through presupposed violence in private
      places. Adolescents were raped by unknown individuals, under serious threat, in
      nondomestic places.

PMID- 14647848
TI  - [Endoscopic supraglottoplasty in children with severe laryngomalacia with and
      without neurological impairment]
AB  - OBJECTIVE: To describe indications and results of supraglottoplasty for severe
      laryngomalacia in children with or without neurological impairment. METHODS:
      Eight children with severe laryngomalacia submitted to endoscopic
      supraglottoplasty were retrospectively studied. Four had neurological impairment
      (male, mean age 6 years), and 4 did not present neurological problems (3 female,
      mean age 11.5 months). Surgery indications were respiratory distress, feeding
      difficulties, failure to thrive, and low oxygen saturation. Polysomnographic
      evaluation was carried out on the last 2 children, showing abnormal oxygen
      saturation, obstructive apnea, and hypoventilation. All children received
      preoperative antibiotics and corticosteroids. RESULTS: All children without
      neurological impairment had significant relief of symptoms. Children with
      neurological impairment had different outcome: one needed tracheotomy immediately
      after surgery due to edema and supraglottic granulation tissue. The other three
      children presented initial relief of symptoms, but subsequent follow-up showed
      progressive airway obstruction: one needed another endoscopic surgery 6 months
      later; other needed tracheotomy 7 months later. The children who were not
      submitted to tracheostomy presented persistent severe airway obstruction. No
      endoscopic surgery complication was observed. CONCLUSIONS: 1) Endoscopic
      supraglottoplasty is well tolerated and does not present complications when used
      in children; 2) Endoscopic supraglottoplasty was efficient in the treatment of
      children with severe laryngomalacia and in without neurological impairment;
      however, supraglottoplasty did not resolve airway obstruction in children with
      neurological impairment.

PMID- 14647849
TI  - [Recessive type of Freeman-Sheldon syndrome - report of two affected siblings]
AB  - OBJECTIVE: To share knowledge and information about the peculiarities of the
      Freeman-Sheldon syndrome, especially concerning the high risk of recurrence of
      its recessive type in siblings, and to stress the importance of genetic
      counseling for families after the birth of an affected child. DESCRIPTION: The
      authors describe and comment two pediatric cases of the Freeman-Sheldon syndrome
      in siblings born to healthy parents. These two cases present significant
      peculiarities that contradict the findings of the medical literature, obtained
      through bibliographic research about the subject. The cases described here
      corroborate the existence of a recessive type of the Freeman-Sheldon syndrome. In
      spite of the fact that some authors suggest a high frequency of severe
      neurological impairment in this type of syndrome, the two cases we analyzed did
      not show any apparent manifestation of such sequelae. COMMENTS: The Freeman
      Sheldon syndrome is heterogeneous not only in its clinical presentation but also
      in its genetic transmission. It is very important to be informed about the
      existence of more than one form of hereditary transmission of this syndrome,
      since genetic counseling should take into consideration all possibilities. In
      these cases, the use of empiric risks of recurrence would be justified.

PMID- 14647850
TI  - [A perspective on the control of myositis ossificans progressiva]
AB  - OBJECTIVE: To report four cases of myositis ossificans progressiva, its form of
      presentation, in addition to new control and treatment options. DESCRIPTION: The
      authors describe four cases of myositis ossificans progressiva, presenting its
      clinical manifestations, evolution, and available forms of control and treatment.
      The main congenital anomalies associated with myosistis ossificans progressiva
      are described, namely: hallux valgus, clinodactyly, short thumbs, exostosis, and
      syndactyly. The evolution and therapeutic responses of clinical improvement to
      oral ascorbic acid and biphosphonate in patients 1 and 4 are also described;
      patient 1 had a better response after receiving intravenous biphosphonate, while
      patients 2 and 3 showed clinical improvement after the administration of oral
      ascorbic acid. COMMENTS: Ascorbic acid relieves the pain and improves psychism in
      patients with myositis ossificans progressiva. Intravenous biphosphonate is an
      alternative to patients with significant worsening of the disease, especially
      those with ambulatory restrictions. The orientation towards avoiding recurrent
      trauma in myositis ossificans progressiva patients is important.

PMID- 14647851
TI  - [Jornal de Pediatria on-line: first impressions]

PMID- 14647852
TI  - [Influence of colostrum on normal bacterial colonization of the neonatal
      gastrointestinal tract]

PMID- 14647854
TI  - [Be patient with science]

PMID- 14647853
TI  - [Why children with severe obstruction of the airway who are attended in the
      emergency department are different]

PMID- 14647855
TI  - [A "natural experiment" regarding the mortality of very low birth weight infants]

PMID- 14647856
TI  - [The influence of smoking on fertility, pregnancy and lactation]
AB  - OBJECTIVE: To decribe the influence of smoking on different phases of the
      reproductive process, fecundation, pregnancy and lactation, drawing special
      attention to the mechanisms of action of the main toxic components found in
      cigarettes. To suggest prophylactic measures for environmental control and how to
      reduce childrens exposure to tobacco smoke. METHODS: Nonsystematic literature
      review using MEDLINE database. RESULTS: Smoking has a negative effect on
      different phases of the reproduction process, by direct action of main toxic
      components, nicotine and carbon monoxide. Smoking reduces fertility, compromises
      the length of gestation and infant birthweight. Smoking mothers also have reduced
      breast milk production and shorter lactation, which affects infant weight gain
      through unclear mechanisms in which prolactin may probably be involved.
      CONCLUSIONS: Smoking compromises reproductive function quality in different
      phases, acting mainly on intrauterine and extrauterine development of infants.
      Since during pregnancy and lactation women are in closer contact with health
      professionals, antismoking campaigns should be especially addressed to this
      period.

PMID- 14647857
TI  - [Human colostrum: a natural source of probiotics?]
AB  - OBJECTIVE: The aim of the present study was to obtain data on the microbiota of
      human colostrum, and to correlate it with a possible source of probiotics
      transferred from mother to infant during breastfeeding. METHODS: 70 samples of
      milked human colostrum were analyzed as to the presence of mesophylic,
      thermoduric, psychrotrophic, proteolytic, proteolytic-psychrotrophic, lipolytic
      microorganisms, molds and yeasts, Staphylococcus aureus, total coliforms, fecal
      coliforms, Group D Streptococcus species and lactic acid bacteria. RESULTS: the
      microbiological analyses revealed several classical groups of microorganisms:
      mesophylic (68.6%); thermoduric (38.6%); psychrotrophic (8.6%); proteolytic
      (15.7%); proteolytic-psychrotrophic (1,4%); lipolytic (4.3%); molds and yeasts
      (11.4%); Staphylococcus aureus (44.3%); total coliforms (7.2%); and lactic acid
      bacteria (37.2%), thus characterizing a diversified microbiota. Thermoduric
      psychrotrophic microorganisms, fecal coliforms and Group D Streptococcus species
      were not identified in any of the samples. CONCLUSIONS: The results show a
      microbiota rich in lactic acid bacteria, which may work as probiotics if
      delivered to infants within the first days of life.

PMID- 14647858
TI  - [Inflammatory mediators, cell counts in nasal lavage and computed tomography of
      the paranasal sinuses in atopic children]
AB  - OBJECTIVE: The aims of this study were to evaluate inflammatory cells, the
      profile of inflammatory mediators in nasal lavage (NL), and the involvement of
      the paranasal mucosa in atopic infants with no symptoms of sinusitis. METHODS: 48
      atopic patients with allergic rhinitis (AR), and 33/48 patients with asthma were
      studied; the control group consisted of 13 nonatopic children. Those individuals
      with acute, chronic or recurrent sinusitis were excluded. The involvement of the
      paranasal mucosa was assessed by coronal computed tomography (CT) and graded by a
      standard protocol (0-30). A CT score greater than or equal to 12 indicated
      extensive involvement. Nasal lavage was used to quantify total and differential
      nasal cell counts. An aliquot of the supernatant was used for determining
      inflammatory mediators: interleukin-8 (IL-8), myeloperoxidase (MPO), and
      eosinophil cationic protein (ECP). Albumin was used as a marker for increased
      vascular permeability. These measurements were performed on all of the atopic
      patients and in 6/13 patients in the control group. The three groups were
      submitted to spirometry and complete blood cell count. RESULTS: Extensive
      involvement of the paranasal mucosa was observed in 7/33 (21%) of asthmatic
      patients (Group I) and 2/15 (13%) of those with allergic rhinitis (Group II). The
      highest CT score in the control group (Group III) was 7. Total cell and
      eosinophil count/ml and albumin concentration in nasal fluid were higher in
      asthmatic patients whose CT score was greater than 12. Interleukin-8
      concentration, number of neutrophils and epithelial cells/ml in nasal fluid were
      similar in the three groups. A positive correlation between CT score, peripheral
      blood eosinophilia, number of eosinophils/ml and eosinophil cationic protein
      concentration was found in the nasal fluid of atopic children (n=48). There was
      an association between number of neutrophils and titers of interleukin-8 and
      myeloperoxidase, and between interleukin-8 and eosinophil count. CONCLUSIONS: in
      asthmatic patients with no symptoms of sinusitis, the extensive involvement of
      the paranasal mucosa is associated with blood and nasal lavage eosinophilia and
      cellular activation. Neutrophil infiltration and activation were not related to
      increased involvement of the paranasal mucosa.

PMID- 14647859
TI  - [Randomized clinical trial of intravenous magnesium sulfate versus salbutamol in
      early management of severe acute asthma in children]
AB  - OBJECTIVE: To study the efficacy of intravenous magnesium sulfate and intravenous
      salbutamol in the treatment of severe asthma in children. METHODS: Randomized,
      double-blind, placebo-controlled clinical trial, including children above 2 years
      of age with severe acute asthma admitted to the observation ward of the Pediatric
      Intensive Care Unit of Hospital Sao Lucas. All patients received conventional
      treatment (oxygen, corticoids, beta-adrenergics) on admission, and later received
      one of the following solutions: a) IVMg (50 mg/kg); b) intravenous salbutamol (1
      micro g/kg); c) saline solution. Clinical assessments, electrolyte concentration,
      and arterial blood gas analyses were recorded before intravenous infusion and one
      hour after that. RESULTS: Fifty patients participated in this study (of whom 53%
      were females, mean age = 4.5 years). There were no significant differences among
      the three groups. The group that received IVMg presented lower blood pressure
      during administration, which reached normal levels one hour afterwards, along
      with an increase in serum magnesium (P<0,001) and serum pH, and reduction of
      PaCO(2). The group that received intravenous salbutamol had lower respiratory
      rate (P=0.05) and higher blood pressure (P=0.01), and one hour after
      administration, these patients showed decreased respiratory rate (P=0.02); lower
      levels of serum potassium (P=0.009); higher pH, and reduced PaCO(2). This group
      required fewer nebulizations (P=0.009), fewer nebulizations per day (P<0.001) and
      less oxygen therapy than the IVMg and placebo groups. Acidosis was more
      persistent (P<0.01) in the placebo group. No difference as to the length of
      hospital stay was observed in any of the three groups. Artificial ventilation was
      necessary in 10% of the patients. CONCLUSIONS: The early intravenous
      administration of magnesium sulfate, especially salbutamol, achieved a rapid
      clinical response with excellent prognosis and no significant side effects.

PMID- 14647860
TI  - [Obesity and malnutrition in children: profile of a low-income community]
AB  - OBJECTIVE: To establish the nutritional diagnosis of children living in a low
      income community through anthropometric evaluation, detecting insufficient
      nutrition (low weight-for-age, wasting and stunting) and excessive nutrition
      (overweight and obesity). METHODS: A community-based survey identified children
      below 11 years living in a low-income community. Their weight and height (or
      lengths) were measured. The National Center for Health Statistics growth curve
      was used as reference. The cut-off points used were: low-weight-for-age z score
      of < -2 (weight-for-age), wasting (weight-for-height) and stunting (height-for
      age); respective overweight and obesity z scores of +1 to +2 and of > +2,
      according to weight-for-height. RESULTS: Prevalence rates were 3.8% for low
      weight for age, and 24% for low-weight-for-age risk factors; 1.2% for wasting,
      and 21.6% for wasting risk factors; 5% for stunting, and 14.3% for stunting risk
      factors; 10.1% for overweight, and 4.6% for obesity. CONCLUSIONS: Main
      nutritional issues were present in children from that community, with
      simultaneous occurrence of chronic malnutrition and obesity.

PMID- 14647861
TI  - [Risk factors for neonatal death in Recife: a case-control study]
AB  - OBJECTIVE: Neonatal mortality is the main cause of infant mortality in the city
      of Recife. The objective of the present study was to determine the major risk
      factors for neonatal death in Recife in 1995. METHODS: This is a case control
      study. Information was obtained from the mortality and live birth databases after
      validation of the data set, between January and December 1995. A sample of 456
      cases and 2,280 controls was obtained after using the linkage technique between
      the two data sets. The difference in proportion was analyzed by the chi square
      test. The odds ratio was calculated as a risk measure, with a 95% confidence
      interval. The logistic regression technique was used to adjust potential
      confounding factors. RESULTS: 212 deaths (46.6%) occurred in the first 24 hours
      of life. We found that 358 (79.7%) of the cases presented low birth weight, with
      a 46-fold higher risk of death (CI =33.8-59.0 P<0.001) than those weighing >/=
      2,500g. The major risk factors observed in the logistic regression analyses of
      the measure, listed in descending order, were: birth weight < 1,500g (OR= 49.6
      CI= 22.6-108.7 P<0.001), 5-minute Apgar score < 7 (OR = 44.1 CI= 25.1-77.2
      P<0.001), birth weight between 1,500 and 2,500g (OR= 8.2 CI= 4.8-14.0 P<0.001),
      gestational age < 37 weeks (OR= 4.3 CI= 2.6-7.1 P<0.001). CONCLUSIONS: Among the
      studied variables, birth weight, gestational age, and Apgar score should be
      considered the main risk factors for the surveillance of neonatal death.

PMID- 14647862
TI  - [IgG antibody response against Plasmodium vivax in children exposed to malaria,
      before and after specific treatment]
AB  - OBJECTIVE: To assess the IgG antibody response against P. vivax (IgG anti-PV),
      and cytophilic (IgG1 and IgG3) and noncytophilic (IgG2) IgG subclasses in 34
      children aged 0 to 15 years old infected with P. vivax malaria. METHODS: IgG
      levels were determined by indirect fluorescent antibody technique during the
      acute and therapeutic control phase. Patients were distributed into 2 groups
      according to the presence or absence of a previous malaria episode. IgG anti-PV
      levels were measured on the first and last day of treatment, and compared by
      Studentacute;s t test. Antibody levels were correlated with asexual parasitemia
      (Spearmans correlation test). RESULTS AND CONCLUSIONS: Increased IgG levels were
      observed on the first and on the last day of treatment. The geometric means for
      IgG subclass titers found in patients with previous history of malaria were: IgG1
      (806.35) > IgG3 (28.28) > IgG2 (20). In patients infected for the first time, the
      responses obtained were: IgG1 (709.21) > IgG3 (39.3) > IgG2 (10.7). There was no
      association between asexual parasitemia and antibody levels on the first day of
      treatment. Cytophilic antibodies (IgG1, IgG3) predominated over noncytophilic
      antibodies (IgG2).

PMID- 14647863
TI  - [Role of nitric oxide synthase in the etiopathogenesis of hypertrophic pyloric
      stenosis in infants]
AB  - OBJECTIVE: To experimentally reproduce, in rats, the findings corresponding to
      the histopathology of infantile hypertrophic pyloric stenosis (IHPS), using
      nitric oxide synthase (NOS) inhibitor (L-NAME). METHODS: L-NAME was administered
      to pregnant rats (L-NAME group), from the 14th gestational day on in order to
      reproduce the model of NOS inhibition in the production of IHPS. This group was
      then compared to control animals. After birth, all the animals in the L-NAME
      group were maintained under NOS inhibition until the 42nd day of life, when they
      were sacrificed. The control animals, which did not receive any kind of drug,
      were also sacrificed on the 42nd day of life. The animals and their internal
      organs were analyzed and weighed. The pyloric region was technically prepared and
      observed through light microscopy. RESULTS: The L-NAME group presented lower body
      and intestinal weight and higher gastric weight than the control group. Light
      microscopy revealed hypertrophy of the circular smooth muscle layer of the
      pyloric muscle in L-NAME animals. CONCLUSIONS: This work reproduced an
      experimental model of an IHPS study, confirming the effect of NOS blockade on the
      pyloric musculature.

PMID- 14647864
TI  - [Health care of very low birth weight infants in Montevideo, Uruguay: a
      comparison between public and private sectors]
AB  - OBJECTIVE: To compare morbidity and mortality in very low birthweight infants
      admitted to public and private intensive care units in Montevideo, Uruguay.
      METHODS: Longitudinal design. All very low birth weight infants born in public
      hospitals of Montevideo between May 1st and October 31st, 1999, were included in
      the study and followed up until they were discharged from hospital, or died. The
      quality of care, and morbidity and mortality rates obtained in private intensive
      care units were compared with those observed in public intensive care units
      (infants who were never transferred). RESULTS: Of 141 infants, 19 were excluded
      from the study (13 died at the delivery room and six were transferred to
      intensive care units of other public hospitals). Of the remaining 122 infants, 61
      were kept at the intensive care units of public hospitals, and 61 were
      transferred to a private unit. The infants who were transferred presented lower
      gestational age and increased neonatal depression. However, mortality among
      infants treated at intensive care units of public hospitals was twice as high
      (Hazard Ratio 1.8; 95%CI 1.1-3.4; P=0.04), especially in infants who weighed less
      than 1,000g (Hazard Ratio 2.4; 95%CI 1.1-5.5; P=0.04). CONCLUSIONS: The health
      status of very low birth weight infants treated at intensive care units of public
      and private hospitals in Montevideo, Uruguay, was assessed. Mortality was lower,
      and health care was better in neonatal units of private hospitals.

PMID- 14647865
TI  - [Study of the frequency of diabetes mellitus and glucose intolerance in patients
      with cystic fibrosis]
AB  - OBJECTIVE: To evaluate the frequency of diabetes mellitus and glucose intolerance
      in patients with cystic fibrosis treated at the Pediatric Gastroenterology
      Service of HC-FMRP-USP. METHODS: A cross-sectional analytical study was conducted
      on a group of 25 patients with mucoviscidosis who were followed up at HC-FMRP
      USP. Oral glucose tolerance tests (OGTT) were performed, with simultaneous
      determination of glycemia and insulinemia. Areas under the curve were obtained
      for glycemia (G) and insulinemia (I) and the I/G ratio was calculated and
      correlated with the duration of clinical manifestation and pancreatic exocrine
      function. RESULTS: Five patients presented alterations: one was diabetic and four
      had glucose intolerance and/or hyperinsulinemia. There was a direct correlation
      between the area under the curve for insulinemia and the duration of
      mucoviscidosis. A significant inverse correlation was also observed between the
      area under the curve for insulinemia and I/G ratio, and number of enzyme
      capsules/kg/day. CONCLUSIONS: The frequency of alterations in glucose homeostasis
      observed in patients with mucoviscidosis was higher than in the population at
      large (20% of the total sample and 33% of the group of patients with glycemia and
      insulinemia on OGTT). Therefore, it is important that glucose tolerance tests be
      performed systematically in patients with mucoviscidosis so that metabolic
      abnormalities can be early detected, and proper treatment can be initiated.

PMID- 14647866
TI  - [Color vision in school children: evaluation of a new test]
AB  - OBJECTIVE: To compare standard color vision test results (Ishihara test) with a
      new test developed by the authors ("crayon" test) for the detection of congenital
      dyschromatopsia. METHODS: Cross-sectional study of 712 children from three public
      schools and one private school in the city of Porto Alegre, state of Rio Grande
      do Sul. Children with learning disabilities, or systemic and ocular diseases were
      excluded from this random sample. Two color vision tests, Ishihara test (short
      version with 14 plates) and crayon test (developed by the authors) were
      sequentially applied. Each test was applied by different evaluators and analyzed
      by a third evaluator. RESULTS: The crayon test showed a specificity of 100% (99.3
      100%) and sensitivity of 38.5% (15.1-67.7%) when compared to Ishihara test. The
      prevalence of congenital dyschromatopsia in this population sample was 2.6% for
      male children, and 0.9% for female children. CONCLUSIONS: The crayon test results
      showed greater specificity than Ishihara test in the studied group; however,
      sensitivity was not adequate for a screening test. It is necessary to improve the
      sensitivity so that congenital dyschromatopsia can be detected by the crayon
      test.

PMID- 14647867
TI  - [Glucose-6-phosphate dehydrogenase deficiency with recurrent infections: case
      report]
AB  - OBJECTIVE: To report a case of rare neutrophil functional disorder with clinical
      and laboratory findings similar to those of chronic granulomatous disease.
      METHODS: Patient with extremely reduced level of glucose-6-phosphate
      dehydrogenase and recurrent infections that improved after continuous use of
      cotrimoxazole. The patient presented leukocytes with defective respiratory burst,
      similar to what occurs in chronic granulomatous disease. COMMENTS: The diagnosis
      of glucose-6-phosphate dehydrogenase deficiency in neutrophils should be
      considered in any patient with hemolytic anemia whose level of G6PD is extremely
      low or in any patient that presents recurrent infections as differential
      diagnosis of chronic granulomatous disease.

PMID- 14647868
TI  - [Hyponatremic coma as a manifestation of Addisons disease]
AB  - OBJECTIVE: To show the importance of severe hydroelectrolytic disorder as a
      consequence of previously undiagnosed chronic disease. DESCRIPTION: Case report
      of hyponatremic coma caused by adrenal crisis in a child with previously
      undiagnosed Addisons disease despite suggestive clinical findings of this disease
      in the last four years. After correction of severe hyponatremia, mild
      hypovolemia, hypernatriuria and hyperkalemia, the differential diagnosis of this
      hydroelectrolytic disorder revealed an adrenal crisis resulting from a primary
      chronic adrenal insufficiency. Oral treatment with hydrocortisone was efficient
      in correcting the metabolic disorder and the patient was then discharged.
      COMMENTS: It is very important to highly suspect of Addisons disease in order to
      avoid the dangerous consequences of late diagnosis such as severe
      hydroelectrolytic disorders and retarded growth and development.

PMID- 14647869
TI  - Advances in angiography and their impact on endovascular therapy.
AB  - Transvascular therapy has progressed rapidly due to improvements in imaging
      equipment and endovascular devices. Interventional fluoroscopic equipment and
      portable machines are able to produce high-resolution digital images in well
      lighted procedure rooms. Catheters and guidewires are now available in a variety
      of shapes, diameters and lengths, allowing entry into distal, small, and tortuous
      vessels. This in turn permits targeted local therapy of tumors and bleeding
      sites, as well as endovascular treatment of diseased vessels.

PMID- 14647870
TI  - Duplex ultrasonography and its impact on providing endograft surveillance.
AB  - Increasingly, aortic aneurysms are being repaired using endoluminal grafting
      techniques. Complications of such surgery include persistent endoleaks, continued
      growth of the aneurysm and migration or thrombosis of the device. Consequently,
      patients undergoing endovascular repair must be under rigorous surveillance
      postoperatively. Spiral computed tomography scanning is the test of choice to
      assess the integrity of the repair, but frequent scanning subjects the patient to
      repeated doses of radiation and nephrotoxic contrast agents. Duplex ultrasound
      has long been used to diagnose the presence of aortic aneurysm and may be an
      appropriate tool for monitoring endovascular grafts. However, the wide
      variability in sensitivity, specificity, positive and negative predictive values,
      and accuracy rates described in the literature reflect the fact that many
      problems still exist with this technique. Until these difficulties can be
      resolved, duplex ultrasonography is best used in conjunction with spiral computed
      tomography.

PMID- 14647871
TI  - Impact of CT angiography on endovascular therapy.
AB  - In the last ten years, computed tomography (CT) angiography has evolved from an
      experimental diagnostic tool to the preferred imaging study for a variety of
      disease processes. At the same time, endovascular surgery has become the first
      line therapy for several types of peripheral vascular disease. With the recent
      introduction of multidetector computed tomography, CT angiography of the entire
      peripheral vascular system is possible in mere seconds. This imaging modality has
      become critical for the pre-procedure planning and post-procedure follow-up of
      several endovascular procedures, including endovascular aneurysm repair, lower
      extremity revascularization, and renal artery revascularization. A thorough
      knowledge of the current applications of CT angiography with respect to the
      peripheral vasculature is essential for the endovascular specialist.

PMID- 14647872
TI  - New techniques and applications for magnetic resonance angiography.
AB  - Recent technological advances in magnetic resonance imaging have transformed the
      field of magnetic resonance angiography (MRA) from a research tool into an
      important clinical examination that is gaining acceptance as the screening
      modality of choice in evaluation of vascular disease. This article describes some
      of the new techniques and applications of MRA in clinical practice today.

PMID- 14647873
TI  - Devices and techniques for endovascular surgery: catheters, stents, coated
      stents, and stented grafts.
AB  - Endovascular/minimally invasive surgery has undergone rapid innovation and
      growth. From crude, stiff, large-bore tubes that were used initially to evaluate
      vascular structures, some of the new catheters and wires are only a little bigger
      than the human hair, which permits their passage in vessels previously thought
      inaccessible. Closed arteries and veins now can be effectively traversed and
      blood flow restored by the use of balloons and metallic stents to maintain the
      integrity of the vascular lumen.

PMID- 14647874
TI  - Endovascular therapy for atherosclerotic occlusion and stenosis from the
      infrarenal aorta to the infrapopliteal arteries.
AB  - Aortoiliac and peripheral vascular disease that cannot be treated medically is
      generally treated by vascular surgeons and/or interventional radiologists.
      Advances in technology have allowed endovascular therapy to become a therapeutic
      option for atherosclerotic disease from the aorta to the femoropopliteal region.
      Distal peripheral disease is still approached surgically; however, further
      technological advances may lead to a more active role for endovascular therapy at
      this level.

PMID- 14647875
TI  - Revascularization of aortic arch branches and visceral arteries using minimally
      invasive endovascular techniques.
AB  - Minimally invasive techniques as the first line of management in vascular
      reconstruction are beginning to replace older surgical techniques. General and
      specific approaches in the endovascular reconstruction of branches off the aortic
      arch (innominate and subclavian arteries) and the visceral branches off the
      abdominal aorta (renal and mesenteric arteries) are described. The branches of
      the aortic arch and the visceral arteries are discussed together because of the
      similarity in the interventional techniques used for revascularization. Patient
      selection, endoluminal techniques, complications, and patient management will
      also be discussed.

PMID- 14647876
TI  - Endovascular repair of diffuse atherosclerotic occlusive disease using stented
      grafts.
AB  - Minimally invasive techniques have greatly influenced the practice of surgery in
      the past two decades, especially the vascular surgical specialty. Current
      technological advances and refinements have allowed for the application of less
      invasive or percutaneous endovascular techniques to the treatment of arterial
      aneurysms and peripheral vascular occlusive disease. While balloon angioplasty
      and stenting for occlusive disease have proven successful in certain vascular
      beds (such as common iliac arteries), infrainguinal results are generally less
      impressive. This paper reviews the results of the application of covered stent
      grafts to peripheral arterial occlusive disease, both at the aortoiliac and
      infrainguinal anatomical levels. The review includes the results of iliac artery
      stented graft placement utilizing a combined open surgical and endovascular
      technique at Mount Sinai Medical Center.

PMID- 14647877
TI  - Drug-eluting stents in peripheral vascular disease: eliminating restenosis.
AB  - Transcatheter endovascular therapy for peripheral atherosclerotic disease has
      become more popular. In general, good results have been reported in focal
      aortoiliac disease. However, the long-term patency of angioplasty in longer, more
      distal lesions has been less satisfactory. Stenting has not been shown to improve
      long-term patency compared to angioplasty alone. Drug-eluting stents have shown
      promise in preventing coronary restenosis, and preliminary results in peripheral
      arterial disease are encouraging. This review article will discuss the current
      status of endovascular therapy of aortoiliac and femoropopliteal atherosclerotic
      disease, the theoretic and experimental basis for the use of drug-eluting stents,
      and the preliminary results in human studies.

PMID- 14647878
TI  - Endovascular treatment of abdominal aortic aneurysms.
AB  - Minimally invasive endovascular techniques for the treatment of abdominal aortic
      aneurysm have significantly reduced its morbidity compared to that following
      standard surgical repair. Moreover, patients with extensive comorbid medical
      illnesses, for whom standard operative repair is contraindicated may be
      successfully treated using endovascular means. The full limitations and
      indications for use of endovascular grafts have not yet been fully defined. The
      effectiveness of commercially fabricated devices is currently being evaluated.
      This article describes the general principles of use for endovascular devices for
      the repair of abdominal aortic aneurysms and details the features of the devices
      currently in use, as well as the typical results.

PMID- 14647879
TI  - Bone density, body composition and menstrual history of sedentary female former
      gymnasts, aged 20-32 years.
AB  - Few studies have examined the effects of retirement from sports involving
      regular, high impact and weight bearing activity on bone mass. This cross
      sectional study compared total body and regional areal bone mineral density
      (aBMD, g/cm(2)) within female former gymnasts and women who had never
      participated in structured sport or exercise, and explored relations between aBMD
      of these former gymnasts and their duration of retirement. Eighteen sedentary
      female former gymnasts (GYM) and 18 sedentary controls (CON) were recruited. GYM
      displayed a broad range of duration of retirement (3-12 years) and a wide age
      range (20-32 years). GYM and CON were paired individually to match for age, body
      mass and stature. GYM had commenced training at least 3 years pre-menarche and
      had trained post-menarche for 2 or more years. They had trained continuously for
      5-12 years and had retired between age 14 and 22 years. Measurements of aBMD and
      body composition were made using dual energy X-ray absorptiometry (DXA). Group
      mean values of physical and skeletal characteristics were compared using paired t
      tests. Linear regression was used to explore possible relations of aBMD within
      GYM to duration of retirement. GYM displayed a higher aBMD than CON at all
      measurement sites, which ranged in magnitude from 6% for the total body (
      P=0.004), to 11% for the total femur ( P=0.006). Elevations of aBMD within GYM
      equated to T-scores ranging from +0.8 (arms) to +1.7 (legs). There were no
      differences in body composition or age of menarche between groups, although 11 of
      18 GYM reported a history of irregular menses. There was no significant decline
      of aBMD with increasing duration of retirement in GYM. The results suggested that
      an elevated bone mass in female former gymnasts was retained during early
      adulthood, in spite of a cessation of training for up to 12 years.

PMID- 14647881
TI  - Abstracts of the 28th Annual meeting of the International Urogynecological
      Association. Buenos Aires, Argentina, 28-31 October 2003.

PMID- 14647880
TI  - Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year
      randomized, double blind, placebo-controlled study.
AB  - The aim of this study was to evaluate the efficacy of pulsed estrogen therapy
      (intranasal 17beta-estradiol) in the prevention of postmenopausal bone loss. A
      total of 386 women (40-65 years old), less than 5 years past menopause, were
      randomized to intranasal placebo, 17beta-estradiol 150 micro g, or 300 micro g
      daily for 2 years. Women with an intact uterus received micronised progesterone
      200 mg per day, 14 days of each 28-day cycle. Women randomised to placebo
      treatment received placebo progesterone. The primary endpoints were changes in
      BMD at the spine (L2-L4) and femoral neck. Secondary endpoints were changes in
      bone turnover markers: serum osteocalcin (sOC) as a marker of bone formation and
      urinary C-terminal telopeptides (uCTX) as a marker of bone resorption. BMD
      increased at all measured sites in women receiving active treatment in a dose
      related manner, the difference compared to placebo being 5.2% and 6.7% at the
      spine, and 3.2% and 4.7 % at the hip, respectively, with 150 microg and 300
      microg ( P<0.001). On the other hand, a decrease versus baseline of -3.2% and 
      3.3% at the spine and hip, respectively, was observed in women receiving placebo
      ( P<0.001). In the patients with at least one risk factor for osteoporotic
      fracture, the difference between placebo and 150 microg or 300 micro g was even
      higher at the spine (5.4% and 7.4%, respectively), and at the femoral neck (4.0%
      and 5.2%, respectively). Correspondingly, uCTX decreased from baseline by 39% and
      46 %, and sOC by 22% and 27%, in the 150 micro g group and 300 micro g group (all
      P<0.001 versus placebo). A strong correlation was found between variations of
      bone turnover markers after 1 year and BMD after 2 years, emphasizing that bone
      markers can predict BMD response during hormonal treatment. Acceptability and
      general tolerance were good. This study demonstrates that pulsed estrogen therapy
      at the dose of 150 microg and 300-microg per day prevents bone loss in a dose
      dependant manner at each site studied, and normalizes bone turnover markers to
      premenopausal levels.

PMID- 14647882
TI  - Cystectomy and orthotopic ileal neobladder in a male patient 12 years after
      kidney transplantation; good preservation of the renal function.
AB  - In case of cystectomy, some forms of urinary diversion can impair the graft
      function of renal transplant patients. Here we present the case of a 70-year-old
      male with carcinoma of the bladder 12 years after renal transplantation.
      Immunosuppression was achieved with Cyclosporin A (200 mg/day) and Prednisone (5
      mg/day). The patient's serum creatinine level was 1.4 mg/dl. Following
      cystectomy, an orthotopic ileal neobladder was constructed by means of Studer
      technique, and the afferent ileal loop was anastomosed to the graft ureter.
      Pathology revealed pT1 G3 N+ transitional cell carcinoma. Ten months later,
      periaortic nodal recurrences necessitated four cycles of chemotherapy with
      Epidoxorubicyn and Gemcytabine. To date, 20 months after cystectomy, the patient
      is stable, with day and night-time urinary continence. His serum creatinine level
      is 1.3 mg/dl, and there is no evidence of hydronephrosis or acidosis. We conclude
      that the orthotopic ileal neobladder is an effective form of urinary diversion in
      renal transplant patients requiring cystectomy, allowing good preservation of the
      renal function.

PMID- 14647883
TI  - Assessment of ventricular contractile function during orthotopic liver
      transplantation.
AB  - Hemodynamic alterations are a well-known phenomenon that influence the outcome of
      orthotopic liver transplantation (OLT). Whether or not myocardial dysfunction,
      which has various causes, contributes to this instability is still debated.
      Previous transesophageal echocardiography (TEE) studies have presented
      controversial data, not leading to final clarification. This is mainly because
      the impact of other contributing factors (inotropic support, alternating preload
      conditions and temperature) remained unaccounted for. We therefore measured the
      left ventricular shortening fraction (LVSF), a parameter reflecting myocardial
      contractility, in 10 consecutive patients undergoing OLT without veno-venous
      bypass. We measured during preparation (PP), during the anhepatic (AP) phase and
      the immediate reperfusion phase (RP). During the AP we observed a significant
      decrease of LVSF which never fell to subnormal levels in the majority of our
      patients, whereas during the RP, LVSF returned to PP values. These findings
      support the assumption that myocardial function is influenced by OLT, but that it
      plays only a minor role in the occurrence of hemodynamic instability, which could
      mainly be attributed to volume fluctuations.

PMID- 14647885
TI  - Cooling heat stroke patients by available field measures.

PMID- 14647884
TI  - Airway colonisation in long-term mechanically ventilated patients. Effect of semi
      recumbent position and continuous subglottic suctioning.
AB  - OBJECTIVE: To evaluate the impact of continuous subglottic suctioning and semi
      recumbent body position on bacterial colonisation of the lower respiratory tract.
      DESIGN: A randomised controlled trial. SETTING: The ten-bed medical ICU of a
      French university hospital. PATIENTS: Critically ill patients expected to require
      mechanical ventilation for more than 5 days. INTERVENTIONS: Patients were
      randomly assigned to receive either continuous suctioning of subglottic
      secretions and semi-recumbent body position or to receive standard care and
      supine position. MEASUREMENTS AND RESULTS: Oropharyngeal and tracheal secretions
      were sampled daily and quantitatively cultured. All included patients were
      followed up from day 1 (intubation) to day 10, extubation or death. Ninety-seven
      samples of oropharynx and trachea were analysed (40 for the suctioning group and
      57 for the control group). The median bacterial counts in trachea were 6.6 Log10
      CFU/ml (interquartile range, IQR, 4.4-8.3) in patients who received continuous
      suctioning and 5.1 Log10 CFU/ml (IQR 3.6-5.5) in control patients. Most of the
      patients were colonised in the trachea after 1 day of mechanical ventilation (75%
      in the suctioning group, 80% in the control group). No significant difference was
      found in the daily bacterial counts in the oropharynx and in the trachea between
      the two groups of patients. CONCLUSION: Tracheal colonisation in long-term
      mechanically ventilated ICU patients was not modified by the use of continuous
      subglottic suctioning and semi-recumbent body position.

PMID- 14647887
TI  - Norepinephrine compromises intestinal microvascular perfusion?

PMID- 14647886
TI  - The pathogenesis of catheter-related bloodstream infection with noncuffed short
      term central venous catheters.
AB  - OBJECTIVE: Short-term, noncuffed, percutaneously inserted central venous
      catheters (CVCs) are widely used and cause more than 250,000 bloodstream
      infections (BSIs) in hospitals each year in the United States. We report a
      prospective study undertaken to determine the pathogenesis of CVC-related BSI.
      DESIGN AND SETTING: Prospective cohort study in a university hospital 24-bed
      medical-surgical intensive care unit. PATIENTS AND PARTICIPANTS: Patients
      participating in two randomized trials during 1998-2000-one studying the efficacy
      of a 1% chlorhexidine-75% alcohol solution for cutaneous antisepsis and the other
      a novel chlorhexidine-impregnated sponge dressing-formed the study population;
      CVC-related BSIs were considered to be extraluminally acquired if concordance was
      identified solely between isolates from catheter segments, skin, and blood
      cultures and intraluminally acquired if concordance was demonstrated only between
      hub or infusate and blood culture isolates, as confirmed by DNA subtyping of
      isolates from blood and catheter sites or infusate. RESULTS: Of 1,263 catheters
      (6075 CVC days) prospectively studied, 35 (2.7%) caused BSI (5.9 per 1000 CVC
      days); 27 were caused by coagulase-negative staphylococci. Overall, 45% of
      infections were extraluminally acquired, 26% were intraluminally derived, and the
      mechanism of infection was indeterminate in 29%. In the pooled control groups of
      the two trials, 25 CVC-related BSIs occurred (7.0 per 1000 CVC days), of which
      60% of infections were extraluminally acquired, 12% were intraluminally derived
      and 28% were indeterminate. In contrast, CVC-related BSIs in the treatment groups
      were most often intraluminally derived (60%, p=0.006). CONCLUSIONS: Most catheter
      related BSIs with short-term percutaneously inserted, noncuffed CVCs were
      extraluminally acquired and derived from the cutaneous microflora. Strategies
      achieving successful suppression of cutaneous colonization can substantially
      reduce the risk of catheter-related BSI with short-term CVCs.

PMID- 14647888
TI  - Intensive care admission decisions for a patient with limited survival prospects:
      a questionnaire and database analysis.
AB  - OBJECTIVE: To explore the concept of futility by asking clinicians for estimates
      of survival and admission decisions for an intensive care unit patient with
      little chance of survival, and to compare these estimates with results from an
      intensive care database. DESIGN: Questionnaire based on the presenting features
      of a genuine patient. It asked for estimated hospital survival, decision on
      intensive care admission, resuscitation status and importance of family views.
      Analysis of a regional intensive care database. SETTING: Physicians working in
      British intensive care units. PARTICIPANTS: We received 169 replies, 146 from
      consultants. MEASUREMENTS AND RESULTS: Median estimated hospital survival was 5%;
      60% of consultants and 76% of trainees would have admitted the patient, with 9%
      and 14%, respectively, prepared to perform further cardiopulmonary resuscitation.
      Among those estimating survival probability as less than 1%, 17.2% would have
      admitted the patient. Family opinions were vital to 4.3% of respondents and
      unimportant to 9.8%. There were 251 patients in the database with similar
      physiological derangements. Their observed hospital mortality was 91%. At
      intensive care admission an admitting physician assessed 111 of these patients as
      'expected to die'. Mortality in this group was 99.1% (one survivor). CONCLUSIONS:
      Experienced intensivists did not agree on estimated survival. Even when estimates
      agreed, admission decisions varied. Database analysis suggested that clinical
      judgement is relevant when assessing the risk of dying. Lack of consensus on
      survival estimates and admission decisions suggests that it would be difficult to
      achieve agreement on appropriate use of intensive care resources and on what
      constitutes futile treatment.

PMID- 14647889
TI  - Breathing pattern variability: a weaning predictor in postoperative patients
      recovering from systemic inflammatory response syndrome.
AB  - OBJECTIVE: To investigate whether breathing pattern variability can serve as a
      potential weaning predictor for postoperative patients recovering from systemic
      inflammatory response syndrome (SIRS). DESIGN AND SETTING: A prospective
      measurement of retrospectively analyzed breathing pattern variability in a
      surgical intensive care unit. PATIENTS: Seventy-eight mechanically ventilated
      SIRS patients who had undergone abdominal surgery were included when they were
      ready for weaning. They were divided into success (n=57) and failure (n=21)
      groups based upon their weaning outcome. MEASUREMENTS AND RESULTS: Before
      weaning, tidal volume, total breath duration, inspiratory time, expiratory time,
      and peak inspiratory flow were continuously monitored for 30 min, while patients
      received 5 cmH2O pressure support weaning trial. After the patients successfully
      completed the trial, they were extubated. Successful weaning was defined as
      patients free from the ventilator for over 48 h, whereas a weaning failure was
      considered as reinstitution of mechanical ventilation within 48 h of extubation.
      The coefficient of variation and two values of standard deviation (SD1 and SD2;
      indicators of the dispersion of data points in the plot) obtained from the
      Poincare plot of five respiratory parameters in the failure group were
      significantly lower than those in the success group. The area under the receiver
      operating characteristic curve of these variability indices was within the range
      of 0.73-0.80, indicating the accuracy of prediction. CONCLUSIONS: Small breathing
      pattern variability is associated with a high incidence of weaning failure in
      postoperative patients recovering from SIRS, and this variability may potentially
      serve as a weaning predictor.

PMID- 14647890
TI  - Factors determining the appearance of glucose in upper and lower respiratory
      tract secretions.
AB  - OBJECTIVES: (a). To describe the glucose content of normal human airways
      secretions; (b). to observe the effects of hyperglycemia and airways inflammation
      on airways glucose. DESIGN: Observational studies. SETTINGS: (a). St George's
      Hospital Medical School; (b). diabetes mellitus outpatient clinics; (c). adult
      general intensive care unit. PATIENTS: Nineteen healthy volunteers, 24 volunteers
      with acute rhinitis, 20 patients with diabetes mellitus, and 60 patients admitted
      to a general adult intensive care unit. MEASUREMENTS: (a). Non-ventilated
      patients: simultaneous measurement of blood and nasal glucose concentrations;
      (b). ICU patients: simultaneous blood, nasal, and endotracheal (ET) glucose
      concentrations. RESULTS: Nasal glucose was undetectable in all healthy
      volunteers. Glucose was detected in 12/24 volunteers with acute viral rhinitis [1
      (1-2) mmol l(-1)] and 18/20 people with diabetes [4 (2-7) mmol l(-1)]. Glucose
      was detected in the ET secretions of 31/60 ventilated patients on ICU. Patients
      with ET glucose had significantly higher blood glucose (9.8+/-0.4 mmol l(-1))
      than patients without ET glucose (7.2+/-0.3 mmol l(-1), P<0.001), and all
      patients with blood glucose >10.1 mmol l(-1) had glucose in ET secretions.
      Enteral nutrition did not affect the presence or concentration of glucose in ET
      secretions. CONCLUSIONS: Glucose is not normally present in airways secretions,
      but appears where hyperglycaemia or epithelial inflammation occur. The detection
      of glucose cannot reliably be used to detect enteral feed aspiration.

PMID- 14647891
TI  - Prone ventilation following witnessed pulmonary aspiration: the effect on
      oxygenation.
AB  - OBJECTIVE: Pulmonary aspiration is a significant cause of admission to the ITU
      and is associated with significant morbidity and mortality. Aspiration in the
      supine position produces posterior collapse/consolidation, similar to that seen
      in ALI/ARDS patients. Prone positioning has been shown to improve oxygenation in
      ALI/ARDS, but no studies have been performed on pulmonary aspiration. DESIGN: A
      prospective crossover study. SETTING: Twelve-bed ITU. PATIENTS AND PARTICIPANTS:
      Eleven patients admitted to ITU with respiratory failure secondary to witnessed
      pulmonary aspiration requiring ventilation and an FIO(2) >0.50 after 12 h.
      INTERVENTIONS: Patients were placed in a prone position for 8 h and then turned
      supine for 8 h. Prone positioning was repeated if the FIO(2) remained >0.50.
      Ventilator settings were not altered in the study period. MEASUREMENTS AND
      RESULTS: Arterial blood gas analysis was performed every 2 h. The PaO(2)/FIO(2)
      gradient was calculated. Oxygenation improved on turning prone, with a
      significant increase in the PaO(2)/FIO(2) ratio ( P<0.01). There was a fall in
      this gradient on return to the supine position. There was a significant
      improvement in oxygenation on turning prone for the second period ( P<0.01).
      Overall, there was a significant improvement in the PaO(2)/FIO(2) ratio in the
      final supine position when compared to the first ( P<0.05). CONCLUSION: This
      study demonstrates a significant improvement in oxygenation in the prone position
      in pulmonary aspiration. Early prone positioning in patients with pulmonary
      aspiration requiring ventilation may improve oxygenation by altering V/Q
      relationships similarly to ARDS, but also may aid drainage of secretions, opening
      up alveoli and preventing progression to established pneumonitis.

PMID- 14647892
TI  - Superior renoprotective effects of combination therapy with ACE and AGE
      inhibition in the diabetic spontaneously hypertensive rat.
AB  - AIMS/HYPOTHESIS: Diabetic renal disease has been postulated to progress as a
      result of an interaction between metabolic and haemodynamic pathways. Our aim was
      to assess the functional, structural, molecular and cellular aspects of renal
      disease in an experimental model of diabetes with associated hypertension.
      METHOD: Streptozotocin-induced diabetic spontaneously hypertensive rats were
      randomised to no treatment, the ACE inhibitor, perindopril (2 mg/l), the AGE
      formation inhibitor, aminoguanidine (1 g/l) and a combination of both agents and
      were followed for 32 weeks. RESULTS: Diabetes was associated with a considerable
      increase in albumin excretion rate. Both aminoguanidine and perindopril retarded
      the increase in albuminuria, which was completely abrogated by combination
      therapy. Glomerulosclerosis and tubulointerstitial damage was reduced by both
      monotherapies with further renoprotection afforded by combination therapy in both
      cases. Combination therapy was also associated with a superior restoration in
      diabetes-induced nephrin protein depletion compared to either monotherapy.
      TGFbeta1 expression as assessed by in situ hybridisation was increased in the
      diabetic rats and reduced by perindopril and aminoguanidine.
      CONCLUSION/INTERPRETATION: These findings indicate that in the context of
      diabetes-related renal injury, blocking both the renin-angiotensin and advanced
      glycation pathways offers superior renoprotection and could be considered as a
      therapeutic strategy in the prevention and retardation of progressive-diabetic
      renal injury.

PMID- 14647893
TI  - Post-prandial triglyceride profile in a population-based sample of Type 2
      diabetic patients.
AB  - AIMS/HYPOTHESIS: Postprandial lipaemia is considered an emerging risk factor for
      cardiovascular disease also in the Type 2 diabetic population. However, little
      information exists on the daily triglyceride profile of these patients,
      especially during everyday life. The aim of the study was to evaluate the daily
      triglyceride profile of Type 2 diabetic patients during their everyday life.
      METHODS: 145 Type 2 diabetic patients (66 men/79 women, age range 45-65 years) at
      a health district near Naples, Italy, participating in a screening survey for the
      evaluation of diabetic complications, and 30 non-diabetic subjects of the same
      area underwent four daily capillary triglyceride profiles by Accutrend (Roche)-a
      previously validated method. RESULTS: Triglyceride values (mmol/l; Means +/- SE)
      were 2.22+/-0.08 at fasting, decreased before lunch (2.03+/-0.07), reached a peak
      3 h after lunch (2.73+/-0.09) and remained substantially high before dinner
      (2.47+/-0.09) (all p<0.001 vs fasting). The triglyceride profile of non-diabetic
      subjects was significantly lower at each point (average difference of 0.73
      mmol/l). The percentage of patients with values above 2.25 mmol/l was 61% 3 h
      after lunch and 49% before dinner. Moreover, in 30% of patients with optimal
      fasting values (<1.69 mmol/l) triglyceride concentrations 3 h after lunch ranged
      between 1.69 and 2.25 mmol/l, and in 31% they were above 2.25 mmol/l.
      CONCLUSION/INTERPRETATION: Most Type 2 diabetic patients have postprandial
      triglycerides above optimal concentrations for several hours after meals.
      Moreover, optimal fasting concentrations are not always a good predictor of
      postprandial triglycerides.

PMID- 14647894
TI  - Birthweight of offspring and paternal insulin resistance and paternal diabetes in
      late adulthood: cross sectional survey.
AB  - AIMS/HYPOTHESIS: It has been proposed that genetic factors involved in insulin
      action could explain part of the link between low birthweight and risk of
      cardiovascular disease and diabetes in adulthood. To confirm this we examined the
      association between offspring birthweight and paternal insulin resistance and
      diabetes in late adulthood. METHODS: We did a cross-sectional survey of 4252 men
      who were 60 to 79 years of age and from 24 British towns. Of these, 2788 men
      provided details of their offsprings' birthweight and sex. RESULTS: Offspring
      birthweight was inversely associated with paternal insulin resistance defined by
      the homeostasis model assessment (HOMA) score and with Type 2 diabetes in late
      adulthood. Fathers of offspring in the highest quartile of sex-standardised
      birthweight SD scores had a 34% reduction in odds of having a high HOMA insulin
      resistance score (OR=0.66, 95% CI: 0.47 to 0.92) compared with fathers of
      offspring in the lowest quartile after adjustment for potential confounders. A
      stronger inverse association was seen between offspring birthweight and risk of
      paternal diabetes (adjusted OR=0.59, 95% CI: 0.39 to 0.88 top quartile vs lowest
      quartile). For each increase of offspring-birthweight SD score the odds of high
      HOMA scores decreased by 13% (OR=0.87, 95% CI: 0.78 to 0.98) and the odds for
      diabetes by 17% (OR=0.83, 95% CI: 0.72 to 0.95), after full adjustment.
      CONCLUSIONS/INTERPRETATION: Offspring birthweight is inversely associated with
      paternal insulin resistance and diabetes in late adulthood, supporting the
      hypothesis that genetic factors related to insulin action contribute to the
      association between birthweight and adult cardiovascular disease and diabetes
      risk.

PMID- 14647895
TI  - TNF-alpha acts to prevent occurrence of malformed fetuses in diabetic mice.
AB  - AIMS/HYPOTHESIS: Activation of apoptosis in embryos is thought to be a key event
      in the pathogenesis of diabetes-induced embryopathies such as early embryonic
      death and inborn structural anomalies. TNF-alpha can activate apoptotic and anti
      apoptotic signalling cascades, indicating its ability to contribute to and
      counteract diabetes-induced maldevelopment. To investigate how TNF-alpha
      regulates the response of embryos to diabetes-induced embryopathic stress, we
      used streptozotocin-induced diabetic TNF-alpha knockout mice. MATERIALS: To
      evaluate the reproductive performance, mated diabetic female mice were examined
      on days 4 and 8 of pregnancy for the presence of blastocysts or embryos in
      uterine horns. To evaluate the teratogenic effect, the female mice were killed on
      day 18 of pregnancy and fetuses were examined for gross external anomalies. In
      addition, apoptotic nuclei were localised by the TUNEL assay and DNA-binding
      activity of the transcription factor NF-kappaB was evaluated by electrophoretic
      mobility shift assay in 10- and 11-day-old embryos respectively. RESULTS:
      Severely diabetic TNF-alpha(+/+) female mice had a much greater decrease in
      pregnancy rate but a lower incidence of malformed fetuses in litters than
      severely diabetic TNF-alpha(-/-) female mice. Also, the intensity of excessive
      apoptosis was higher, but the amount of active NF-kappaB complexes was lower in
      malformed TNF-alpha(-/-) embryos than in TNF-alpha(+/+) embryos.
      CONCLUSIONS/INTERPRETATION: TNF-alpha contributes to death of peri-implantation
      embryos and possibly protects postimplantation embryos exposed to diabetes
      induced teratogenic stimuli via activation of NF-kappaB-mediated anti-apoptotic
      signalling. It seems that TNF-alpha prevents the birth of malformed offspring in
      severely diabetic mice.

PMID- 14647897
TI  - Genetic analysis and molecular mapping of maize (Zea mays L.) stalk rot resistant
      gene Rfg1.
AB  - One single pathogen Fusarium graminearum Schw. was inoculated to maize inbred
      lines 1,145 (Resistant) and Y331 (Susceptive), and their progenies of F(1), F(2)
      and BC(1)F(1) populations. Field statistical data revealed that all of the F(1)
      individuals were resistant to the disease and that the ratio of resistant plants
      to susceptive plants was 3:1 in the F(2) population, and 1:1 in the BC(1)F(1
      )population. The results revealed that a single dominant gene controls the
      resistance to F. graminearum Schw. The resistant gene to F. graminearum Schw. was
      denominated as Rfg1 according to the standard principle of the nomenclature of
      the plant disease resistant genes. RAPD (randomly amplified polymorphic DNA)
      combined with BSA (bulked segregant analysis) analysis was carried out in the
      developed F(2) and BC(1)F(1 )populations, respectively. Three RAPD products
      screened from the RAPD analysis with 820 Operon 10-mer primers showed the linkage
      relation with the resistant gene Rfg1. The three RAPD amplification products (OPD
      20(1000), OPA-04(1100) and OPY-04(900)) were cloned and their copy numbers were
      determined. The results indicated that only OPY-04(900) was a single-copy
      sequence. Then, OPY-04(900) was used as a probe to map the Rfg1 gene with a RIL
      F(7) mapping population provided by Henry Nguyen, which was developed from the
      cross "S3xMo17". Rfg1 was primarily mapped on chromosome 6 between the two linked
      markers OPY-04(900) and umc21 (Bin 6.04-6.05). In order to confirm the primary
      mapping result, 25 SSR (simple sequence repeat) markers and six RFLP (restriction
      fragment length polymorphism) markers in the Rfg1 gene-encompassing region were
      selected, and their linkage relation with Rfg1 was analyzed in our F(2)
      population. Results indicated that SSR marker mmc0241 and RFLP marker bnl3.03 are
      flanking the Rfg1 gene with a genetic distance of 3.0 cM and 2.0 cM,
      respectively. This is the first time to name and to map a single resistant gene
      of maize stalk rot through a single pathogen inoculation and molecular marker
      analysis.

PMID- 14647898
TI  - Characterization and molecular genetic mapping of microsatellite loci in pepper.
AB  - Microsatellites or simple sequence repeats are highly variable DNA sequences that
      can be used as informative markers for the genetic analysis of plants and
      animals. For the development of microsatellite markers in Capsicum,
      microsatellites were isolated from two small-insert genomic libraries and the
      GenBank database. Using five types of oligonucleotides, (AT)(15), (GA)(15),
      (GT)(15), (ATT)(10) and (TTG)(10), as probes, positive clones were isolated from
      the genomic libraries, and sequenced. Out of 130 positive clones, 77 clones
      showed microsatellite motifs, out of which 40 reliable microsatellite markers
      were developed. (GA)(n) and (GT)(n) sequences were found to occur most frequently
      in the pepper genome, followed by (TTG)(n) and (AT)(n). Additional 36
      microsatellite primers were also developed from GenBank and other published data.
      To measure the information content of these markers, the polymorphism information
      contents (PICs) were calculated. Capsicum microsatellite markers from the genomic
      libraries have shown a high level of PIC value, 0.76, twice the value for markers
      from GenBank data. Forty six microsatellite loci were placed on the SNU-RFLP
      linkage map, which had been derived from the interspecific cross between Capsicum
      annuum "TF68" and Capsicum chinense "Habanero". The current "SNU2" pepper map
      with 333 markers in 15 linkage groups contains 46 SSR and 287 RFLP markers
      covering 1,761.5 cM with an average distance of 5.3 cM between markers.

PMID- 14647896
TI  - Conserved simple sequence repeats for the Limnanthaceae (Brassicales).
AB  - The Limnanthaceae (Order Brassicales) is a family of 18 taxa of Limnanthes
      (meadowfoam) native to California, Oregon, and British Columbia. Cultivated
      meadowfoam ( L. alba Benth.), a recently domesticated plant, has been the focus
      of research and development as an industrial oilseed for three decades. The goal
      of the present research was to develop several hundred simple sequence repeat
      (SSR) markers for genetic mapping, molecular breeding, and genomics research in
      wild and cultivated meadowfoam taxa. We developed 389 SSR markers for cultivated
      meadowfoam by isolating and sequencing 1,596 clones from L. alba genomic DNA
      libraries enriched for AG(n) or AC(n) repeats, identifying one or more unique
      SSRs in 696 clone sequences, and designing and testing primers for 624 unique
      SSRs. The SSR markers were screened for cross- taxa utility and polymorphisms
      among ten of 17 taxa in the Limnanthaceae; 373 of these markers were polymorphic
      and 106 amplified loci from every taxon. Cross-taxa amplification percentages
      ranged from 37.3% in L. douglasii ssp. rosea (145/389) to 85.6% in L. montana
      (333/389). The SSR markers amplified 4,160 unique bands from 14 genotypes sampled
      from ten taxa (10.7 unique bands per SSR marker), of which 972 were genotype
      specific. Mean and maximum haplotype heterozygosities were 0.71 and 0.90,
      respectively, among six L. alba genotypes and 0.63 and 0.93, respectively, among
      14 genotypes (ten taxa). The SSR markers supply a critical mass of high
      throughput DNA markers for biological and agricultural research across the
      Limnanthaceae and open the way to the development of a genetic linkage map for
      meadowfoam ( x = 5).

PMID- 14647899
TI  - An intraspecific genetic map of velvetbean (Mucuna sp.) based on AFLP markers.
AB  - Velvetbean ( Mucuna sp., n=11), a self-pollinated species, is an important legume
      used in tropical agricultural systems in rotation with other crops for nematode
      management and/or soil improvement. A genetic map of velvetbean was constructed
      in order to identify potential molecular markers linked to important
      morphological and agronomic traits that would be particularly useful for
      developing and improving the species. Traits such as seed coat color, pod color,
      and pod pubescence were among the main parameters observed in a process of
      genetic diversity estimation. Two slightly divergent velvetbean accessions,
      PI364362 and 'Edgar Farm White', a land race from Alabama, were used to make an
      intraspecific F(1) hybrid. Amplified fragment length polymorphism analysis (AFLP)
      detected an average of six polymorphic fragments per primer pair between the two
      parents. As expected for dominant markers, the sum of all AFLP bands from both
      parents was generally observed to be present in the AFLP profiles of the F(1)
      progeny, indicating full penetrance and the dominant nature of AFLP markers. An
      F(2) population was generated by self-pollinating a single F(1) plant. Using 37
      AFLP primer pairs, we detected 233 polymorphic markers of which 164 (70.4%)
      segregated in 3:1 Mendelian ratios, while the remaining 69 (29.6%) both
      segregated and were scorable. The genetic linkage map constructed from this
      population comprised 166 markers, including two morphological traits (pod color
      and pod pubescence). Twenty linkage groups were found with an average distance
      between markers of 34.4 cM, covering a total of 687.9 cM. The linkage groups
      contained from 2 to 12 loci each and the distance between two consecutive loci
      ranged from 0 to 21.8 cM. The newly designated morphological traits pod color (
      pdc) and pod pubescence ( pdp) co-segregated with each other at a distance of 4.2
      cM. Two DNA markers designated ACGCAG2 and ACTCTG1 were located in the same group
      as pdc and pdp. The AFLP linkage map provides opportunities for use in marker
      assisted selection and in the detection of loci controlling morphologically
      important traits.

PMID- 14647900
TI  - Selection of highly informative and user-friendly microsatellites (SSRs) for
      genotyping of cultivated potato.
AB  - Characterization of nearly 1,000 cultivated potato accessions with simple
      sequence repeats (SSRs; also referred to as microsatellites) has allowed the
      identification of a reference set of SSR markers for accurate and efficient
      genotyping. In addition, 31 SSRs are reported here for a potato genetic map,
      including new map locations for 24 of them. A first criterion for this proposed
      reference set was ubiquity of the SSRs in the eight landrace cultivar groups of
      the potato, Solanum tuberosum. All SSRs tested in the present study displayed the
      same allele phenotypes and allele size range in the diverse germplasm set as in
      the advanced potato cultivar germplasm in which they were originally discovered.
      Thirteen of 13 SSR products from all cultivar groups are shown to cross-hybridize
      with the corresponding SSR product of the source cultivar to ascertain sequence
      homology. Other important SSR selection criteria are quality of amplification
      products, locus complexity, polymorphic index content, and well-dispersed
      location on a potato genetic map. Screening of 156 SSRs allowed the
      identification of a highly informative and user-friendly set comprising 18 SSR
      markers for use in characterization of potato genetic resources. In addition, we
      have identified true- and pseudo-multiplexing SSRs for even greater efficiency.

PMID- 14647901
TI  - An EST survey of the sugarcane transcriptome.
AB  - Its large genome and high polyploidy makes sugarcane (Saccharum spp.) a
      singularly challenging crop to study and improve using genetic approaches. To
      provide large numbers of functionally characterized candidate genes that might be
      tested for direct association (rather than distant linkage) with economically
      important traits, we sequenced the 5' ends of 9,216 clones from three cDNA
      libraries (apex, leaf and mature internode), representing 3,401 non-redundant
      sequences. About 57% of these sequences could be assigned a tentative function
      based on statistically significant similarity to previously characterized
      proteins or DNA sequences. Another 28% corresponded to previously identified, but
      uncharacterized, sequences. Some of the remaining unidentified sequences were
      predicted to be genes which could potentially be new to plants or unique to
      sugarcane. Comparisons of the sugarcane ESTs to a large sorghum EST database
      revealed similar compositions of expressed genes between some different tissues.
      Comparison to a detailed Arabidopsis protein database showed some highly
      conserved sequences, which might be useful DNA markers for pan-angiosperm
      comparative mapping. These EST sequences provide a foundation for many new
      studies to accelerate isolation of agronomically important genes from the
      cumbersome sugarcane genome.

PMID- 14647907
TI  - [The trigeminovascular system in the human. Cerebral blood flow, functional
      imaging and primary headache].
AB  - Primary headache syndromes, such as cluster and migraine, are widely described as
      vascular headaches, even though there is considerable clinical evidence to
      suggest that both conditions are primarily central, that is regulated by the
      brain. The shared anatomical and physiological substrate for both clinical
      syndromes is the neural innervation of the cranial circulation. Early functional
      imaging using PET has shed light on the genesis of both syndromes, documenting
      activation in the midbrain and pons in migraine and in the hypothalamic gray in
      cluster headache. These areas are involved in the pain process in a permissive or
      triggering manner rather than simply as a response to first-division nociceptive
      pain impulses. This article reviews findings in the physiology of the
      trigeminovascular system which demand renewed consideration of the neural
      influences in many primary headaches and the physiology of the neural innervation
      of cranial circulation. Primary headaches should thus be regarded as
      neurovascular headaches to emphasize the interaction between nerves and vessels
      which is their underlying characteristic.

PMID- 14647908
TI  - [Hepatic encephalopathy].
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric complication of acute and
      chronic liver disease. Its etiology and pathogenesis are thought to be a complex,
      metabolically induced, and therefore potentially reversible disturbance in brain
      functions. The diagnosis is based on demonstrating both a disorder of the central
      nervous system and a concomitant liver disease as well as the exclusion of any
      neurological or psychiatric disorder of other etiology. The diagnosis of HE is
      clinical and displays a wide spectrum of neuropsychiatric symptoms in different
      degrees of severity. Ancillary diagnostic workup includes laboratory tests,
      neuroimaging, and neurophysiological exams such as electroencephalography and
      evoked potentials. The therapy of HE mainly consists of treatment and avoidance
      of any precipitating conditions such as high protein intake, infections, and
      gastrointestinal bleeding. Other therapeutic approaches modulate metabolic
      processes such as ammonium synthesis and excretion, formation of
      neurotransmitters, and as a last resort liver transplantation. The prognosis
      depends ultimately on the course of the liver disease.

PMID- 14647909
TI  - [Stroke in children and adolescents. Epidemiology--etiology--neurological
      deficits--neuropsychological manifestations].
AB  - Significant epidemiological facts for stroke are different in children and
      adolescents than in adults. A wide range of causes and risk factors are available
      for assessment, which is not the case for older patients. Long-term outcome must
      be regarded by different aspects such as spontaneous remission or the neural
      plasticity of child brain. Stroke in childhood results in neurological and
      specific neuropsychological impairments which depend on phases of brain maturity.
      Special attention should be paid to psychosocial effects of the disease and the
      impairments that result.

PMID- 14647910
TI  - [Antibody-induced failure of botulinum toxin therapy].
AB  - Botulinum toxin (BT) has been used with great success in a large number of
      medical specialities. In some patients, however, formation of antibodies against
      BT (BTAB), with therapy failure (ABTF) occurs. Risk factors for ABTF are the
      amount of BT given at each injection series and the duration of the intervals
      between injection series. Treatment time and cumulative BT dose as well as
      patient age and gender are not independent risk factors. BTAB titres drop
      spontaneously after cessation of BT therapy, but latencies are too long to be
      compatible with a clinically effective therapy. Once these titres have dropped,
      BT therapy can be restarted using improved parameters and improved BT
      preparations with lower antigenicity. Increasing the BT dosage can be successful
      for overcoming ABTF when BTAB titres are low and target muscle responses are only
      moderately reduced. The use of alternative BT type A preparations fails to
      overcome ABTF. Alternative BT types such as types B and F are initially
      successful in ABTF but stimulate the formation of antibodies against the
      alternative BT types after few applications. When type B is used, substantial
      systemic anticholinergic side effects can occur. Prevention of BTAB formation is
      of paramount importance. Risk factors for BTAB formation have to be taken into
      account when planning BT therapy. The most interesting perspective, however,
      seems to be the development of new BT preparations with improved specific potency
      and reduced antigenicity.

PMID- 14647911
TI  - [Analysis of direct costs in therapy of Parkinson disease].
AB  - The increasing prevalence of Parkinson syndrome and its cost-intensive modern
      therapies make for a growing economic burden. Studies on cost to date have
      limited validity owing to the various methods employed (retrospective, focus on
      partial expenses, minimal case numbers, etc.). The present study collected data
      pertaining to direct costs. Seventy-seven patients were followed for 10 months.
      They had been outpatients when enrolled in the study. Hospitalization or
      comparable changes during the course of observation were registered accordingly.
      The most significant result revealed by the study is that expenses for medication
      by far take up the biggest share of the direct costs. In the early stage of the
      disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros.
      With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in
      H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average
      costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47
      Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month,
      medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS),
      and medical services to 15.73 Euros.

PMID- 14647912
TI  - [Long-term life changes and stress sequelae for spouses of stroke patients].
AB  - OBJECTIVE: This study investigates the long-term effect of stroke on the quality
      of life and health of patients' spouses. METHOD: Twenty-six spouses of stroke
      patients were interviewed by means of standardized questionnaires and qualitative
      interviews. The study participants had been living with the consequences of
      stroke for 3 years on average when the interviews were carried out. RESULTS: A
      stroke is often followed by considerable changes in everyday life and by role
      shifts within the relationship. In particular, depressive and aggressive changes
      in the patient's behaviour are experienced as burdensome. In addition to
      impairments in quality of life, psychological and psychosomatic troubles can also
      from the burden experienced. Depressive symptoms are the main factor in these
      negative consequences: the more a patient is assessed as depressive, the more
      his/her spouse reports health problems and poor quality of life. DISCUSSION: Long
      term changes in everyday life and partnership can bring about significant chronic
      burden for the spouses of stroke patients. Hence, offers of support and
      counseling are required not only in the acute and post-acute stages of stroke,
      but also after inpatient rehabilitation has ended.

PMID- 14647913
TI  - [Bacterial meningitis as a complication of Fusobacterium necroforum infection in
      adults].
AB  - Fusobacterium necrophorum, an anaerobic, gram-negative rod, belongs to the
      physiological flora of the oropharynx. It causes Lemierre's syndrome
      characterized by oropharyngeal infection, septic thrombophlebitis of the neck, in
      particular of the internal jugular vein, and metastatic abscesses, predominantly
      in the lungs. Rarely, and mainly in children, it causes meningitis. Here we
      report the clinical course of a 25-year-old woman with F. necrophorum meningitis.
      She presented with incomplete, right third nerve palsy. Within a few days, she
      developed fever, meningism and progressive reduction of vigilance. Cerebrospinal
      fluid analysis showed typical signs of bacterial meningitis. After the
      identification of F. necrophorum, the antibiotic treatment was changed to
      meropenem, which led to continuous improvement of the clinical symptoms. Due to
      persistent signs of inflammation in the CSF, metronidazole was added to the
      antibiotic regime. This case report demonstrates that F. necrophorum should
      always be considered in the diagnostic workup of bacterial meningitis in adults.

PMID- 14647914
TI  - [Cerebral vasospasms with hemodynamic infarctions as a complication of HELLP
      syndrome].
AB  - Sinal thrombosis, intracerebral bleeding, cerebral edema, and cerebral vasospasm
      are typical neurological complications in pre- and eclampsia. Hemolysis, elevated
      liver enzyme, and low platelet (HELLP) syndrome is a rare, severe complication of
      pre-eclampsia. We present the case of a 33-year-old woman with HELLP syndrome.
      After a cesarean section, generalized epileptic seizure occurred and intubation
      was necessary due to sustained unconsciousness. Despite magnesium therapy,
      bilateral hemodynamic ischemic infarctions and narrowing of the circle of Willis
      were visible on MRI, and vasospasm of all large basal cerebral arteries was
      confirmed by cerebral angiography and transcranial Doppler sonography. During the
      following 2 weeks, the cerebral vasospasm resolved with application of high-dose
      methyl prednisolone and nimodipine. After extubation, the patient initially
      suffered from mild psychosyndrome and ataxia but recovered completely after 3
      months. The HELLP syndrome may be complicated by cerebral vasospasm with
      subsequent hemodynamic strokes. Combined treatment with magnesium,
      corticosteroids, and nimodipine can be recommended. In our case, this regimen led
      to resolution of the cerebral vasospasm and complete clinical recovery.

PMID- 14647915
TI  - [Pigmented form of orthochromatic leukodystrophy].
AB  - The pigmentary type of orthochromatic leukodystrophy (van Bogaert-Nyssen disease)
      is a hardly known neurological disorder usually with late onset that is very
      difficult to diagnose in vivo. Neuropathologically, the disorder features
      noninflammatory demyelination and the presence of pigmented macrophages and
      astrocytes that may contain iron. Clinically, van Bogaert-Nyssen disease can lead
      to death within a few years and is characterized by dementia, psychiatric
      abnormalities, epileptic seizures, spastic pareses, and occasionally
      extrapyramidal motor symptoms. This report presents a typical case and an
      overview of the literature. Furthermore, galactocerebroside could be documented
      in remaining macrophages and astrocytes by immunohistochemistry. This possibly
      indicates a dysfunction in sphingolipid breakdown and could relate the pigmented
      form of orthochromatic leukodystrophy to the genetically defined globoid cell
      leukodystrophy (Krabbe's disease). Thus, the rather heterogeneous pool of
      orthochromatic leukodystrophies could be further narrowed.

PMID- 14647916
TI  - [Neuroprotection in brain tumors. Good sense or nonsense from the
      pathophysiological viewpoint?].
AB  - The hemodynamic and metabolic state of peritumoral brain tissue is not well
      understood, especially with subtotal or total, extraluminal compression of the
      carotid artery or other main intracranial vessels of the central nervous system.
      Possibly, parallels can be drawn from the knowledge in chronically malperfused
      brain tissue of atherosclerotic disease in sub- or nearly total stenosis of the
      internal carotid artery. From this point of view, it seems that the CBF/CBV
      quotient and oxygen extraction rate represent an additional diagnostic method-if
      needed in combination with the well-established balloon occlusion test-to help to
      better characterize the grade of still viable peritumoral brain tissue. The
      therapeutic strategy for possible pharmacological neuroprotection should be
      related to these parameters. It remains a matter of debate whether this clinical
      phenomenon will be one of the therapeutic domains influenced by ischemic
      preconditioning in the near-future.

PMID- 14647917
TI  - [Walter Poppelreuter].

PMID- 14647918
TI  - [The Schmidt and Vernet classical syndrome. Alternating brain stem syndromes that
      do not exist?].
AB  - In contrast to the majority of classic brainstem syndromes, the interpretation of
      Schmidt's syndrome (ipsilateral palsy of the IX, X, XI, and XII cranial nerves
      with contralateral hemiparesis) and Vernet's syndrome (ipsilateral palsy of the
      IX, X, and XI nerves with contralateral hemiparesis) is controversial. They are
      sometimes addressed as crossed brainstem syndromes but also as syndromes due to
      multiple cranial nerve lesions without contralateral hemiparesis. In this study,
      the historic descriptions and recent publications about Schmidt's and Vernet's
      syndromes were reviewed and critically analysed. We conclude that historic
      descriptions and later publications describe exclusively patients with
      extracerebral lesions of multiple cranial nerves. "Central" syndromes of Schmidt
      and Vernet caused by brainstem lesion appear not to exist. An extremely extensive
      lesion explaining these hypothetical unilateral brainstem syndromes is
      theoretically possible but, however, was apparently never observed in any of the
      known unilateral brainstem diseases.

PMID- 14647919
TI  - [Narcoleptic dogs. Significance for human narcolepsy].

PMID- 14647920
TI  - The tumor-selective viral protein apoptin effectively kills human biliary tract
      cancer cells.
AB  - Biliary tract cancer, or cholangiocarcinoma, has a poor prognosis. Resection is
      the only curative treatment, but only a minority of patients are eligible.
      Chemotherapy and gamma-irradiation are merely palliative, as they are unable to
      remove the malignancy completely. The chicken anemia virus-derived protein
      apoptin induces apoptosis in a wide range of human tumor cells and is not
      hindered by mutations inactivating p53 or by overexpression of Bcl-2, changes
      known to frustrate chemotherapy and radiation therapy. We examined whether
      apoptin kills human biliary tract cancer cells. Expression of apoptin by means of
      plasmids caused extensive cell death in three independent cholangiocarcinoma cell
      lines, CC-LP, CC-SW, and Mz-ChA-1, regardless of their oncogenic mutations, which
      included inactivated p16 and p53 and the disruption of the transforming growth
      factor beta signaling pathway. In vitro delivery of apoptin by an adenoviral
      vector completely eradicated cholangiocarcinoma cells. Moreover, coexpression of
      the broad-spectrum caspase inhibitor p35 with apoptin only delayed the induced
      cell death. Changes in nuclear morphology still occurred early after
      transfection, and nuclei eventually disintegrated, suggesting that apoptin
      induced cell death in these cells is not blocked by mutations in either the
      initiation or execution phase of apoptosis. The efficient induction of cell death
      by apoptin in cholangiocarcinoma cell lines makes apoptin an attractive candidate
      for molecular therapy of biliary tract cancer.

PMID- 14647921
TI  - Role of insulin-like growth factor I signaling in neurodegenerative diseases.
AB  - Disturbed trophic support to neurons has long been considered a potential
      mechanism in neurodegeneration. Recent evidence indicates that intracellular
      trophic signaling may be compromised in several neurodegenerative diseases.
      Changes in the levels of insulin-like growth factor I (IGF-I), a trophic hormone
      with multiple neuroprotective actions, have recently been observed in several
      human neurodegenerative illnesses. Therefore analysis of IGF-I pathways could
      help provide greater insight into trophic disturbances to neurons. However,
      neurodegenerative diseases with similar clinical manifestations show either high
      or low levels of circulating IGF-I. This apparently puzzling observation can be
      explained if we consider that IGF-I input to target neurons is disrupted by
      either lower IGF-I availability or by reduced cell sensitivity to IGF-I. The
      latter disturbance may be associated with high IGF-I levels. We hypothesize that
      in the majority of neurodegenerative diseases compromised IGF-I support to
      neurons emerges as part of the pathological cascade during the degenerative
      process and contributes to neuronal demise. In addition, loss of IGF-I input to
      specific neuronal populations might be the cause of a small group of
      neurodegenerative diseases.

PMID- 14647922
TI  - Telomere length and telomerase activity during expansion and differentiation of
      human mesenchymal stem cells and chondrocytes.
AB  - Chondrocyte ex vivo expansion currently performed to replace damaged articular
      surfaces is associated with a loss of telomeric repeats similar to decades of
      aging in vivo. This might affect the incidence or time of onset of age-related
      disorders within transplanted cells or tissues. This study examined whether more
      immature progenitor cells, such as mesenchymal stem cells (MSC), which can be
      expanded and subsequently differentiated into chondrocytes is advantageous
      regarding telomere-length related limitations of expansion protocols. Primary
      chondrocytes and bone-marrow-derived MSC were isolated from 12 donors, expanded
      separately to 4 x 10(6) cells, and (re-)differentiated as three-dimensional
      chondrogenic spheroids. Cells were collected during expansion, after three
      dimensional culturing and chondrogenic differentiation, and sequential analyses
      of telomere length and telomerase activity were performed. Surprisingly,
      telomeres of expanded MSC were significantly shorter than those from expanded
      chondrocytes from the same donor (11.4+/-2.5 vs. 13.4+/-2.2 kb) and tended to
      remain shorter after differentiation in chondrogenic spheroids (11.9+/-1.8 vs.
      13.0+/- kb). While telomere lengths in native chondrocytes and MSC were not
      related to the age of the donor, significant negative correlations with age were
      observed in expanded (136 bp/year), three-dimensionally reconstituted (188
      bp/year), and redifferentiated (229 bp/year) chondrocytes. Low levels of
      telomerase activity were found in MSC and chondrocytes during expansion and after
      (re-)differentiation to chondrogenic spheroids. In terms of replicative
      potential, as determined by telomere length, ex vivo expansion followed by
      chondrogenic differentiation of MSC did not provide a benefit compared to the
      expansion of adult chondrocytes. However, accelerated telomere shortening with
      age during expansion and redifferentiation argues for an "age phenotype" in
      chondrocytes as opposed to MSC and suggests an advantage for the use of MSC
      especially in older individuals and protocols requiring extensive expansion

PMID- 14647923
TI  - [Comparative genomic hybridization as cytogenetic tumor diagnosis technique in
      juvenile angiofibroma].

PMID- 14647924
TI  - [Universal neonatal screening as an application of automated audiological
      techniques].

PMID- 14647925
TI  - [Submental transcutaneous electrical stimulation for obstructive sleep apnea].
AB  - BACKGROUND: Transcutaneous electrical stimulation while asleep has been used to
      treat obstructive sleep apnea (OSA), although without convincing results. Modern
      strategies consist of electrical muscle training for a number of weeks during
      wakefulness rather than stimulation during sleep. OBJECTIVE: The purpose of this
      study was to assess the practicability, safety, and efficacy of a new device,
      SilentOne (Imperpuls, Chemnitz, Germany). PATIENTS AND METHODS: Fifteen patients
      with various degrees of OSA used transcutaneous submental electrical stimulation
      therapy for 4-5 weeks every day, day and night. A patient's diary recorded
      practicability and potential adverse events. Respiratory parameters were recorded
      by fully attended polysomnography in the sleep lab. Daytime sleepiness and
      snoring were assessed by questionnaires. RESULTS: The apnea-hypopnea-index
      decreased from 29.2 before to 21.2 after therapy (P<0.05). Daytime sleepiness
      improved significantly (P<0.01) as did snoring (P<0.005). CONCLUSIONS.
      Transcutaneous electrical stimulation therapy using SilentOne proved to be safe,
      easy to use, and potent. However, therapy showed a limited cure rate.

PMID- 14647926
TI  - [Automated hearing threshold estimation in newborns using extrapolated DPOAE
      input/output functions].
AB  - BACKGROUND AND AIM: A new method for automatically assessing hearing loss by
      means of extrapolated DPOAE I/O-functions was applied for the first time in
      newborns. METHODS: DPOAE I/O-functions were recorded in 118 ears of 93 newborns
      (mean age 3 days) at 12 frequencies between 1 and 8 kHz. L(2) was varied between
      20 and 65 dB SPL with L(1)=0.4L(2)+39 and f(2)/f(1)=1.2. Auditory thresholds were
      constructed using the estimated DPOAE threshold level from extrapolated DPOAE I/O
      functions. Follow-up measurements were conducted in 15 ears 4 weeks later.
      RESULTS: The first measurement revealed a high-frequency hearing loss. The second
      measurement showed normal hearing function. This fact and the decrease of DPOAE
      level in the frequency range of the hearing loss, while keeping the compressive
      shape of the DPOAE I/O-functions, indicate that transitory sound conduction
      disturbance may be due to amniotic fluid. CONCLUSIONS: The method fulfils the
      essential criteria for screening newborn hearing. It is fast and easy to handle,
      and measurement and data analysis are performed automatically. Preliminary
      results suggest that the new method is able to differentiate between transitory
      middle-ear dysfunction and persisting cochlear disorders. Due to its better
      diagnostic capabilities in comparison to TEOAE, DPOAE, and FAEP, this method may
      provide a new instrument with which to make a fast evaluation of hearing function
      in children.

PMID- 14647927
TI  - [Chromosomal alterations in juvenile angiofibromas].
AB  - INTRODUCTION: Despite their benign histological appearance, juvenile
      angiofibromas, which occur mainly in adolescent males, have a locally aggressive
      growth pattern. beta-catenin-mutations represent their only known genetic
      abnormality. MATERIAL AND METHODS: Angiofibroma tissue from seven patients was
      available for comparative genomic hybridization (CGH). RESULTS: In six out of the
      seven angiofibromas, CGH detected various abnormalities on 18 different
      chromosomes. Frequent chromosomal gains were observed on chromosomes 4q, 6q, and
      8q. In four out of seven angiofibromas a complete loss of the chromosome Y was
      detected. CONCLUSIONS: CGH is a suitable method for the examination of
      angiofibromas for genetic alterations. Considering the sex distribution of this
      neoplasm, the frequent loss of chromosome Y is of particular interest.

PMID- 14647928
TI  - [Therapeutic management of necrotizing neck infections].
AB  - BACKGROUND: Necrotizing neck infections are uncommon soft-tissue infections,
      usually caused by virulent, toxin producing bacteria. Necrotizing fasciitis
      represents a special form of necrotizing soft tissue infection with a mortality
      rate of up to 76% even though aggressive therapy is recommended. PATIENTS AND
      METHODS: In the last 2 years we treated four patients with severe necrotizing
      neck infections and five suffering from necrotizing fasciitis. RESULTS:
      Microbiological analysis revealed mixed infections with Candida albicans,
      Streptococcus pyogenes, Fusobacterium, Proprioni bacteria and Staphylococcus. The
      surgical management was not only restricted to drainage, but also included
      functional neck dissection in order minimize the spread of the disease. Eight of
      our patients recovered completely, but one died due to toxic shock as consequence
      of a delayed in therapy. CONCLUSION: Complete recovery of patients suffering from
      necrotizing fasciitis depends on early and aggressive surgical therapy including
      neck dissection and drainage as well as an interdisciplinary strategy of
      conservative therapy. Hyperbaric oxygen should be considered as a treatment
      adjunct in patients with necrotizing fasciitis if surgery and antibiotic
      treatment fail.

PMID- 14647929
TI  - [Therapeutic and histological features of basaloid squamous cell carcinoma].
AB  - BACKGROUND AND OBJECTIVE: Basaloid squamous cell carcinoma s a rare, highly
      malignant carcinoma variant typically situated in the tongue base, supraglottis
      and pyriform sinus. It is usually only diagnosed at a very advanced stage due to
      its tendency towards submucosal growth, deep infiltration and early local and
      distant metastases. PATIENTS/METHODS: The case described involves a 39-year-old
      man with the clinical and histopathological findings typical for this neoplasm.
      RESULTS: In contrast to simple squamous cell carcinomas, the basaloid variant
      with its very poor prognosis calls for therapeutic decisions that give particular
      consideration to quality of life. It should be stressed that highly invasive
      surgery is justified only in exceptional cases because of the high local
      recurrence rate and early distant metastases. CONCLUSIONS: The case presented
      shows that radio- and chemotherapeutic approaches are just as important as
      surgery.

PMID- 14647930
TI  - [Fibrous dysplasia of the petrous bone].
AB  - Fibrous dysplasia named after Jaffe and Lichtenstein is a benign, self-limiting
      disorder of the bone structure. The normal bone is replaced by cellular fibrous
      connective tissue. Fibrous dysplasia can be differentiated into monostotic and
      polyostotic forms and the McCune-Albright syndrome (combination of polyostotic
      areas in the bone with hyperpigmentation of the skin and endocrinological
      disturbances). The rare disease is predominantly found in the 1st to 3rd decade
      of life in the femur or humerus. In about 15% of all cases it affects the facial
      bones, and one-third of these is located in the jaw bone. Extremely rare is the
      invasion of the petrous bone. A 45-year-old female patient was examined because
      of tinnitus persisting for 1 year. In addition, she was suffering from increased
      hearing reduction and recurrent vertigo. The CT and MRT showed a milky glass-like
      tumor, which was limited by an osteolytic process situated in the left petrous
      bone. The process was removed via the mastoid. Histological examination revealed
      fibrous dysplasia. A highly differentiated osteosarcoma and an ossifying fibroma
      as important differential diagnoses have to be excluded because of the different
      therapeutic consequences.

PMID- 14647931
TI  - [Recurring bilateral parotid swelling].

PMID- 14647932
TI  - [Hyperacusis, phonophobia, and recruitment. Abnormal deviations of hearing
      associated with hypersensitivity to sound].
AB  - Hypersensitivity to sound is a common description of distinct nosological
      phenomena of peripheral and central hearing disorders, which are characterized by
      intense suffering from the acoustic environment. One can distinguish between
      recruitment accompanying inner ear hearing loss, hyperacusis with a general
      hypersensitivity to sound of any frequency, and phonophobia as an anxious
      sensitivity towards specific sound largely independent of its volume. While
      recruitment can be described as a peripheral reaction caused by a lack of outer
      hair cell moderation, hyperacusis and phonophobia represent disturbances of
      central auditory processing without peripheral pathology, often combined with
      psychosomatic reactions. Due to insufficient efferent inhibition, hyperacusis
      often follows psychovegetative exhaustion. In cases of phonophobia, peripheral
      and efferent hearing functions are usually intact, but certain learning
      (conditioning) processes lead to development of specific reactions and avoidance
      patterns to certain content-related acoustic stimuli. This article describes
      those different phenomena with regard to their clinical appearance, diagnostics,
      and possibilities for therapy.

PMID- 14647933
TI  - [The Oldenburg children's rhyme test during speech simulating noise disturbance
      (Regensburg variant). Modification of the test and normal values for the ages 7
      10 years].
AB  - OBJECTIVE: Of the German language speech audiometry tests used for children, only
      the Oldenburg children's rhyme test is constructed to allow measurements in
      noise. Unfortunately, no reference values exist for such measurements. Many of
      children admitted to test speech discrimination in noise are suspected of
      suffering from central auditory processing disorders and/or attention deficits.
      Thus, the objective of the present study is the development of a speech-in-noise
      test that focuses the children's attention on the target words. DESIGN: A speech
      simulating noise was added to the Oldenburg children's rhyme test and the
      discrimination function was estimated. First, the total power of all target words
      was equalised and the total power of the noise adjusted to obtain a constant
      signal-to-noise ratio (SNR) for all target words. Second, speech and noise were
      presented binaurally with headphones. Speech was presented at 65 dB SPL and the
      noise level varied to obtain SNRs of 0, -5 and -10 dB SN. A total of 55 normal
      children, 7-10 years of age, were also tested. RESULTS: Mean speech
      discrimination was 91+/-7% at 0 dB SN, 75+/-11% at -5 dB SN and 55+/-14% at -10
      dB SN. The discrimination function results in a speech reception threshold (SRT)
      of -10.9 dB SN and a maximum slope of 4.95%/dB SN. CONCLUSION: The "Regensburg"
      variation of the "Oldenburg children's rhyme test" was easily feasible in all
      tested children. The results can be used as normative data for children between 7
      and 10 years.

PMID- 14647934
TI  - Cluster calibration in mass spectrometry: laser desorption/ionization studies of
      atomic clusters and an application in precision mass spectrometry.
AB  - For accurate mass measurements and identification of atomic and molecular species
      precise mass calibration is mandatory. Recent studies with laser
      desorption/ionization and time-of-flight analysis of cluster ion production by
      use of fullerene and gold targets demonstrate the generation of atomic clusters
      for calibration purposes. Atomic ion results from the Penning trap mass
      spectrometer ISOLTRAP, in which a carbon cluster ion source has recently been
      installed, are presented as an application in the field of precision mass
      spectrometry.

PMID- 14647935
TI  - Flow injection chemiluminescence determination of L-cysteine in amino acid
      mixture and human urine with the BrO3--quinine system.
AB  - In this paper, a novel flow injection chemiluminescence (CL) determination of L
      cysteine is proposed. The method is based on the CL reaction of L-cysteine and
      KBrO3 in acidic medium. The CL intensity was greatly enhanced in the presence of
      quinine. The CL intensity was linear with L-cysteine concentration in the range
      of 0.2-80 microg L(-1), and the detection limit was 0.1 microg L(-1) (3 sigma). A
      complete analysis, including sampling and injecting, could be performed in 1 min,
      giving a throughput of about 60 h(-1). The relative standard deviation was 1.6%
      for 0.8 microg L(-1 ) L-cysteine ( n=11). The proposed method was satisfactorily
      applied to the determination of cysteine in an amino acid mixture and human
      urine. The mechanism of the CL reaction is also discussed.

PMID- 14647936
TI  - Chemometric studies of polycyclic aromatic hydrocarbon shape selectivity in
      reversed-phase liquid chromatography.
AB  - The molecular shape recognition differences between monomeric and polymeric C18
      stationary phases in the reversed-phase liquid chromatography (RPLC) separation
      of unsubstituted polycyclic aromatic hydrocarbons (PAHs) and methyl-substituted
      polycyclic aromatic hydrocarbons (MPAHs) are examined through the use of partial
      least squares (PLS) analysis techniques. The resulting PLS models are able to
      describe the enhanced shape selectivity of the polymeric phase for recognizing
      subtle structural differences among planar and nonplanar isomers. PLS component
      analyses of these models reveal that spatial and topological descriptors are
      primarily used to rank structural differences among the PAHs (i.e., fused-ring
      patterns, molecular length and breadth) that control such shape-selective
      chromatographic processes. This is consistent with the view that polymeric alkyl
      chain stationary phases contain size- and shape-specific "slots" that promote the
      separation of structurally-related solutes. In contrast, the monomeric phase
      model is limited in resolving both the isomer classes and the nonplanarity shape
      differences among the PAHs. However, an improvement of shape recognition on the
      monomeric phase was elucidated by the PLS model for two PAHs (phenanthro[3,4
      c]phenanthrene and dibenzo[g,p]chrysene) exhibiting the most extreme
      nonplanarity. These results suggest that a limited amount of space between alkyl
      chains may exist within the higher-density polymeric phase to recognize shape
      differences among the bulkier and nonplanar solutes.

PMID- 14647937
TI  - LC-MS analysis in the aquatic environment and in water treatment--a critical
      review. Part I: Instrumentation and general aspects of analysis and detection.
AB  - LC-MS has become an invaluable technique for trace analysis of polar compounds in
      aqueous samples of the environment and in water treatment. LC-MS is of particular
      importance due to the impetus it has provided for research into the occurrence
      and fate of polar contaminants, and of their even more polar transformation
      products. Mass spectrometric detection and identification is most widely used in
      combination with sample preconcentration, chromatographic separation and
      atmospheric pressure ionization (API). The focus of the first part of this review
      is directed particularly toward instruments and method development with respect
      to their applications for detecting emerging contaminants, microorganisms and
      humic substances (HS). The current status and future perspectives of 1) mass
      analyzers, 2) ionization techniques to interface liquid chromatography (LC) with
      mass spectrometry (MS), 3) methods for preconcentration and separation with
      respect to their application for water analysis are discussed and examples of
      applications are given. Quadrupole and ion trap mass analyzers with electrospray
      ionization (ESI) and atmospheric pressure chemical ionization (APCI) are already
      applied in routine analysis. Time-of-flight (TOF) mass spectrometers are of
      particular interest for accurate mass measurements for identification of
      unknowns. For non-polar compounds, different ionization approaches have been
      described, such as atmospheric pressure photoionization (APPI), electrochemistry
      with ESI, or electron capture ionization with APCI. In sample preconcentration
      and separation, solid phase extraction (SPE) with different non-selective sorbent
      materials and HPLC on reversed-phase materials (RP-HPLC) play the dominant role.
      In addition, various on-line and miniaturized approaches for sample extraction
      and sample introduction into the MS have been used. Ion chromatography (IC), size
      exclusion chromatography (SEC), and capillary electrophoresis (CE) are
      alternative separation techniques. Furthermore, the issues of compound
      identification, matrix effects on quantitation, development of mass spectral
      libraries and the topic of connecting analysis and toxicity bioassays are
      addressed.

PMID- 14647938
TI  - Biosensors for environmental monitoring of endocrine disruptors: a review
      article.
AB  - This article provides an overview of the applications of biosensors in analysis
      and monitoring of endocrine-disrupting compounds (EDCs) in the environment.
      Special attention is devoted to the various types of physical-chemical signal
      transduction elements, biological mechanisms employed as sensing elements and
      techniques used for immobilisation of the bioreceptor molecules on the transducer
      surface. Two different classes of biosensors for EDCs are considered: biosensors
      that measure endocrine-disrupting effects, and biosensors that respond to the
      presence of a specific substance (or group of substances) based on the specific
      recognition of a biomolecule. Several examples of them are presented to
      illustrate the power of the biosensor technology for environmental applications.
      Future trends in the development of new, more advanced devices are also outlined.

PMID- 14647940
TI  - Precise isotope ratio measurements as a unique tool in modern analytical
      chemistry.

PMID- 14647939
TI  - Immunosensor for estrone with an equal limit of detection as common analytical
      methods.
AB  - Immunoanalytical methods at a very low limit of detection (LOD) and a low limit
      of quantification (LOQ) are becoming more and more important for environmental
      analysis and especially for monitoring drinking water quality. Biosensors have
      suitable characteristics such as efficiency in allowing very fast, sensitive, and
      cost-effective detection. Here we describe a fully automated immunoassay for
      estrone with a LOD below 0.20 ng L(-1) and a LOQ below 1.40 ng L(-1). In contrast
      to common analytical methods such as GC-MS or HPLC-MS, the biosensor used
      requires no sample pre-treatment and pre-concentration. The basis of our
      sensitive assay is the antibody with a high affinity constant towards estrone.
      The very low amount of antibody per sample results in low validation parameters
      (LOD, LOQ, and IC50), but this assay for estrone represents the current device
      related limitation of the River Analyser (RIANA).

PMID- 14647941
TI  - Compound-specific stable isotope analysis of organic contaminants in natural
      environments: a critical review of the state of the art, prospects, and future
      challenges.
AB  - Compound-specific stable isotope analysis (CSIA) using gas chromatography-isotope
      ratio mass spectrometry (GC/IRMS) has developed into a mature analytical method
      in many application areas over the last decade. This is in particular true for
      carbon isotope analysis, whereas measurements of the other elements amenable to
      CSIA (hydrogen, nitrogen, oxygen) are much less routine. In environmental
      sciences, successful applications to date include (i) the allocation of
      contaminant sources on a local, regional, and global scale, (ii) the
      identification and quantification of (bio)transformation reactions on scales
      ranging from batch experiments to contaminated field sites, and (iii) the
      characterization of elementary reaction mechanisms that govern product formation.
      These three application areas are discussed in detail. The investigated spectrum
      of compounds comprises mainly n-alkanes, monoaromatics such as benzene and
      toluene, methyl tert-butyl ether (MTBE), polycyclic aromatic hydrocarbons (PAHs),
      and chlorinated hydrocarbons such as tetrachloromethane, trichloroethylene, and
      polychlorinated biphenyls (PCBs). Future research directions are primarily set by
      the state of the art in analytical instrumentation and method development.
      Approaches to utilize HPLC separation in CSIA, the enhancement of sensitivity of
      CSIA to allow field investigations in the microg L(-1) range, and the development
      of methods for CSIA of other elements are reviewed. Furthermore, an alternative
      scheme to evaluate isotope data is outlined that would enable estimates of
      position-specific kinetic isotope effects and, thus, allow one to extract
      mechanistic chemical and biochemical information.

PMID- 14647942
TI  - An optimization procedure for determination of metallothionein by square wave
      cathodic stripping voltammetry: application to marine worms.
AB  - Electrochemical determination of metallothionein (MT) is widely used for
      environmental studies. This article describes the development and optimization of
      the procedure for the quantification of metallothionein by square wave cathodic
      stripping voltammetry. The determination is based on the complexation of
      cisplatin and MT and the subsequent reduction of the complexes at the electrode.
      In order to achieve the highest possible sensitivity and resolution of the peak,
      an optimization of the experimental parameters has been carried out using
      experimental design methodology (response surface). Seven chemical and physical
      parameters, namely, pH, cisplatin concentration, buffer concentration, deposition
      potential, square wave frequency, amplitude of pulse, and step potential, have
      been optimized to give 9.0, 5.9 microM, 0.65 M, -0.2 mV, 229 Hz, 46 mV, and 2 mV,
      respectively. Method characterization has been performed, leading to a detection
      limit of 0.1 microg L(-1). Quantification of MT in polychaetes and comparison
      with the modified Brdicka procedure were also carried out.

PMID- 14647943
TI  - Application of L-cysteine-capped nano-ZnS as a fluorescence probe for the
      determination of proteins.
AB  - Nanometer-sized L-cysteine-capped ZnS particles have been synthesized and used as
      a fluorescence probe to investigate the effect of proteins on fluorescent
      intensity. With Delta lambda=190 nm, maximum and constant synchronous
      fluorescence enhancement was produced at 267 nm and pH 5.12 in the presence of
      proteins. A highly sensitive synchronous fluorescence method for the rapid
      determination of proteins has been developed. Under optimum conditions,
      calibration graphs are linear over the range 0.03-8.0 microg mL(-1) for bovine
      serum albumin (BSA), 0.01-6.0 microg mL(-1) for human serum albumin (HSA), 0.05
      8.0 microg mL(-1) for gamma-globulin (gamma-G), and 0.04-4.0 microg mL(-1) for
      ovalbumin, respectively. The relative standard deviations of seven replicate
      measurements were 1.75% for 1.0 microg mL(-1) BSA, 1.90% for 1.0 microg mL(-1)
      HSA, 1.65% for 1.0 microg mL(-1) gamma-G, and 2.32% for 1.0 microg mL(-1)
      ovalbumin.

PMID- 14647944
TI  - Determination of two intact glucosinolates in vegetables and Chinese herbs.
AB  - A reversed-phase HPLC method was developed for analyzing sinigrin and
      gluconasturtiin in six vegetable and two Chinese herb samples. A gradient program
      and mobile phases using methanol and 0.05% trifluoroacetic acid containing 20 mM
      ammonium acetate allowed sufficient retention and separation of the
      glucosinolates in the sample extracts. Quadrupole time-of-flight tandem mass
      spectrometry in negative ion electrospray ionization was used to analyze the
      fractions collected from the HPLC elution to confirm the identification of the
      glucosinolates. The levels of sinigrin and gluconasturtiin in the vegetables and
      Chinese herbs were determined by using an external calibration method.
      Concentrations of gluconasturtiin in the Chinese herbs were more than 15 times
      higher than those of sinigrin. Detection limits were 18 nmol g(-1) for sinigrin
      and 4 nmol g(-1) for gluconasturtiin when 50 g of fresh vegetable was analyzed.

PMID- 14647945
TI  - Nanoscale proteomics.
AB  - Efforts to develop a liquid chromatography (LC)/mass spectrometry (MS) technology
      for ultra-sensitive proteomics studies (i.e., nanoscale proteomics) are
      described. The approach combines high-efficiency nanoscale LC (separation peak
      capacity of approximately 10(3); 15-microm-i.d. packed capillaries with flow
      rates of 20 nL min(-1), the optimal separation linear velocity) with advanced MS,
      including high-sensitivity and high-resolution Fourier transform ion cyclotron
      resonance MS, to perform both single-stage MS and tandem MS (MS/MS) proteomic
      analyses. The technology enables broad protein identification from nanogram-size
      proteomics samples and allows the characterization of more abundant proteins from
      sub-picogram-size samples. Protein identification in such studies using MS is
      demonstrated from <75 zeptomole of a protein. The average proteome measurement
      throughput is approximately 50 proteins h(-1) using MS/MS during separations,
      presently requiring approximately 3 h sample(-1). Greater throughput
      (approximately 300 proteins h(-1)) and improved detection limits providing more
      comprehensive proteome coverage can be obtained by using the "accurate mass and
      time" tag approach developed in our laboratory. This approach provides a dynamic
      range of at least 10(6) for protein relative abundances and an improved basis for
      quantitation. These capabilities lay the foundation for studies from single or
      limited numbers of cells.

PMID- 14647946
TI  - Isotope-dilution ICP-MS for trace element determination and speciation: from a
      reference method to a routine method?
AB  - This critical review discusses the conditions under which inductively coupled
      plasma-isotope dilution mass spectrometry (ICP-IDMS) is suitable as a routine
      method for trace element and element-speciation analysis. It can, in general, be
      concluded that ICP-IDMS has high potential for routine analysis of trace elements
      if the accuracy of results is of predominant analytical importance. Hyphenated
      techniques with ICP-IDMS suffer both from lack of commercially available isotope
      labeled spike compounds for species-specific isotope dilution and from the more
      complicated system set-up required for species-unspecific ICP-IDMS analysis.
      Coupling of gas or liquid chromatography with species-specific ICP-IDMS, however,
      enables validation of analytical methods involving species transformations which
      cannot easily be performed by other methods. The potential and limitations of ICP
      IDMS are demonstrated by recently published results and by some unpublished
      investigations by our group. It has been shown that possible loss of silicon as
      volatile SiF4 during decomposition of a sample by use of hydrofluoric acid has no
      effect on trace silicon determination if the isotope-dilution step occurs during
      digestion in a closed system. For powder samples, laser ablation ICP-IDMS can be
      applied with an accuracy comparable with that only available from matrix-matched
      standardization, whereas the accuracy of electrothermal vaporization ICP-IDMS was
      strongly dependent on the element determined. The significance of easy synthesis
      of isotope-labeled spike compounds for species-specific ICP-IDMS is demonstrated
      for monomethylmercury and Cr(VI). Isotope-exchange reactions between different
      element species can prevent the successful application of ICP-IDMS, as is shown
      for iodinated hydrocarbons. It is also shown for monomethylmercury that species
      transformations during sample-pretreatment steps can be followed by species
      specific ICP-IDMS without loss of accuracy. A relatively simple and time
      efficient procedure for determination of monomethylmercury in environmental and
      biological samples is discussed. The method, which entails a rapid microwave
      assisted isotope dilution step and in-situ extraction of the derivatized species,
      has good potential for routine application in the future.

PMID- 14647947
TI  - Beam-injection flame furnace AAS: comparison of different nozzle types for beam
      generation and application of sub-critical liquid carbon dioxide as carrier and
      gas pressure pump.
AB  - In beam injection flame furnace AAS (BIFF-AAS) the sample is introduced as a free
      flying high-speed liquid beam into an AAS flame-heated nickel tube, resulting in
      a considerable improvement in the power of detection. For optimization of beam
      generation different nozzle types (smooth jet nozzles, turbulent working nozzles)
      have been compared at different pressures. It was found that the type of the
      nozzle hardly influences the analytical signal. However, the flow rates resulting
      from the different inner diameters of the nozzles and the applied pressures led
      to drastic changes in the analytical signal. For these investigations a recently
      developed 0.6 MPa (84 psig) diaphragm pump system was used. Furthermore, for the
      first time ever sub-critical liquid carbon dioxide has been used simultaneously
      as a liquid gas-pressure pump, as carrier in a flow-injection system (FIA), and
      for the beam generation. Transport of the carrier takes place as a result of the
      head pressure (6 MPa) of the liquid CO2 in the gas cylinder. For volatile
      elements (e.g. Cd, Hg, Pb, and Tl) detection limits between 0.2 microg L(-1) (Cd)
      and 28 microg L(-1) (Hg) were found, the standard deviation was from 0.6% to 3.2%
      depending on the element, concentration, and sample volume used. The use of
      liquid CO2 as a carrier in FIA systems opens up new possibilities for online
      sample pretreatment and trace preconcentration.

PMID- 14647948
TI  - Ninth international symposium on biological and environmental reference materials
      (BERM-9), Berlin, Germany, June 15-19, 2003.

PMID- 14647949
TI  - Determination of rofecoxib, in the presence of its photodegradation product, in
      pharmaceutical preparations by micellar electrokinetic capillary chromatography.
AB  - A simple and rapid micellar electrokinetic capillary chromatographic (MEKC)
      method for analysis of rofecoxib (ROF) and its photodegradation product (PDP) in
      pharmaceutical preparations has been developed and validated. Analyses were
      conducted in a fused silica capillary (72 cm effective length, 50 microm i.d.)
      with a background electrolyte consisting of 25 mmol L(-1) borate buffer at pH 7.0
      containing 15 mmol L(-1) sodium dodecyl sulfate (SDS) and 10% acetonitrile (ACN).
      The separation was performed by voltage-controlled system, applying 30 kV at 30
      degrees C, detecting at 225 nm; injection was hydrodynamic at 50 mbar for 2 s.
      Nifedipine was used as internal standard (IS). Under the optimum conditions ROF,
      PDP, and IS were well separated with in 10 min. The method was validated with
      regard to linearity, limit of detection and quantitation, precision, accuracy,
      specificity, and robustness. The detection limit of the method was low, 0.8
      microg mL(-1), and the linearity range was wide, 2.5 to 125 microg mL(-1). The
      method was highly efficient-5x10(5) plates m(-1) for ROF. The method was applied
      to the tablet form of ROF-containing pharmaceutical preparations. The data were
      compared with those from the voltammetric method described in literature. No
      statistically significant difference was found.

PMID- 14647950
TI  - Study of the feasibility of using a pellicular anion-exchange column for
      separation of transferrin isoforms in human serum by HPLC with UV detection.
AB  - A method has been optimised for the separation of glycoforms of human serum
      transferrin, using a high-performance pellicular anion-exchange chromatographic
      column. The effect of the eluent pH and of the column temperature on the
      separation of transferrin glycoforms was studied using a standard solution of
      commercially available human serum transferrin. An HPLC system equipped with an
      ultraviolet detector was used for the analysis. No immunoassay was used after the
      anion-exchange chromatographic separation of the glycoforms, in contrast with
      most currently used methods. The method was applied to the separation and
      quantification of transferrin glycoforms in serum from a healthy, non-pregnant
      woman, after saturation of transferrin with iron and further precipitation of
      lipoproteins. The whole chromatographic run, including re-equilibration of the
      column, took 35 min.

PMID- 14647951
TI  - Study of a bis-furaldehyde Schiff base copper(II) complex as carrier for
      preparation of highly selective thiocyanate electrodes.
AB  - A new highly selective thiocyanate electrode based on N,N'-bis-(furaldehyde)-1,2
      phenylenediamine-dipicolyl copper(II) complex [Cu(II)-BFPD] as neutral carrier is
      described. The electrode has an anti-Hofmeister selectivity sequence: SCN->I->Sal
      >ClO4->Br->NO2->Cl->NO3->SO4(2-)>SO3(2-)>H2PO4- and a near-Nernstian potential
      linear range for thiocyanate from 1.0x10(-1) to 5.0x10(-6) mol L(-1) with a
      detection limit 2.0x10(-6) mol L(-1) and a slope of 57.5 mV decade(-1) in pH 5.0
      of phosphate buffer solution at 20 degrees C. The response mechanism is discussed
      on the basis of results from A.C. impedance measurement and UV spectroscopy. The
      anti-Hofmeister behavior of the electrode results from a direct interaction
      between the central metal and the analyte ion and a steric effect associated with
      the structure of the carrier. The electrode has the advantages of simplicity,
      fast response, fair stability and reproducibility, and low detection limit. The
      selectivity of electrodes based on [Cu(II)-BFPD] exceeds that of classical anion
      sensitive membrane electrodes based on ion exchangers such as lipophilic
      quaternary ammonium or phosphonium salts. Application of the electrode for
      determination of thiocyanate in waste water samples from a laboratory and a gas
      factory, and in human urine samples, is reported. The results obtained were fair
      agreement with the results obtained by HPLC.

PMID- 14647952
TI  - Fermentation monitoring using multisensor systems: feasibility study of the
      electronic tongue.
AB  - The electronic tongue based on an array of 30 non-specific potentiometric
      chemical sensors has been applied to qualitative and quantitative monitoring of a
      batch fermentation process of starting culture for light cheese production.
      Process control charts were built by using PLS regression and data from
      fermentations run under "normal" operating conditions. Control charts allow
      discrimination of samples from fermentation batches run under "abnormal"
      operating conditions from "normal" ones at as early as 30-50% of fully evolved
      fermentations. The capability of the electronic tongue to quantify concentrations
      of important organic acids (citric, lactic and orotic) in the present type of
      fermentation media was demonstrated. Average prediction errors were assessed in
      the range 5-13% based on test set validation. Correlation between peptide
      profiles determined using HPLC and the electronic tongue output was also
      established. The electronic tongue was demonstrated to be a promising tool for
      fermentation process monitoring and quantitative analysis of growth media.

PMID- 14647953
TI  - Analytical procedures for quantification of peptides in pharmaceutical research
      by liquid chromatography-mass spectrometry.
AB  - Peptide quantification by liquid chromatography-mass spectrometry (LC-MS)
      combines the high resolving power of reversed-phase (RP) chromatography with the
      excellent selectivity and sensitivity of mass spectrometric detection. On the
      basis of comprehensive practical experience in the analysis of small molecules,
      pharmaceutical research is developing technologies for analysis of a growing
      number of peptidic drug candidates. This article is a detailed review of
      procedures based on LC-MS techniques for quantitative determination of peptides.
      With the focus on pharmaceutical applications several technologies for sample
      preparation, various aspects of peptide chromatography, important characteristics
      of ESI-MS, selectivity of MS-detection modes, the large variability of internal
      standards, and modern instrumentation are discussed. The demand for reliable,
      robust, sensitive, and accurate methods is discussed using numerous examples from
      the literature, complemented by experiments and results from our laboratory.

PMID- 14647954
TI  - Structural study of spirolide marine toxins by mass spectrometry. Part I.
      Fragmentation pathways of 13-desmethyl spirolide C by collision-induced
      dissociation and infrared multiphoton dissociation mass spectrometry.
AB  - A novel group of toxins, the spirolides, has been investigated by several mass
      spectrometric (MS) methods to enable structure elucidation and metabolite
      identification. These macrocyclic compounds, produced by the dinoflagellate
      Alexandrium ostenfeldii, are a new class of marine phycotoxin with characteristic
      spiro-linked tricyclic ether and imine moieties. A crude phytoplankton extract
      has been shown to contain known spirolides and several unknown compounds, present
      at low yet significant levels. This study has focused on mass spectrometric
      characterization of the main component of this extract, 13-desmethyl spirolide C.
      Collision-induced dissociation (CID) spectra were collected on triple-quadrupole
      and quadrupole linear ion-trap instruments. High-resolution Fourier-transform ion
      cyclotron resonance MS data revealed the accurate masses of the protonated
      molecule and the product ions formed by infrared multiphoton dissociation. A
      fragmentation scheme for this toxin has been proposed to explain the formation of
      the collision-induced fragments. Charge-remote fragmentations dominate the CID
      spectra, because there is only one predominantly basic site in this molecule, and
      prove to be structurally informative. Extensive MS characterization of 13
      desmethyl spirolide C will undoubtedly be useful in the characterization of known
      and unknown spirolides and other related compounds.

PMID- 14647956
TI  - Alcohol intoxication increases allopregnanolone levels in male adolescent humans.
AB  - RATIONALE: Teenage drinking is a cause of growing concern in industrialized
      countries, where almost 35% of alcohol drinkers are under 16 years old. Increased
      anxiety, irritability and depression among adolescents may induce them to seek
      the anxiolytic and rewarding properties of alcohol. Allopregnanolone is rewarding
      in rodents, and therefore may contribute to the effects of alcohol. OBJECTIVE: In
      this paper, we studied the effects of acute alcohol intoxication on the plasma
      levels of allopregnanolone in male adolescents. METHODS: Blood samples were drawn
      from male adolescents who arrived at the Emergency Department of the Hospital.
      Two groups were studied: one study group was formed by adolescents who arrived
      with evident behavioral symptoms of acute alcohol intoxication (AAI) and the
      other by those arriving for mild trauma (contusions, sprains) after no
      consumption of alcohol (Controls). RESULTS: Our results demonstrate that AAI
      significantly increases serum allopregnanolone levels in male adolescents.
      CONCLUSIONS: Because alcohol and allopregnanolone positively modulate gamma
      aminobutyric acid type A (GABAA) receptors, allopregnanolone may play a major
      role in the anxiolytic and rewarding effects of alcohol, either directly or by
      influencing the sensitivity of GABAA receptors to alcohol.

PMID- 14647955
TI  - Assessing the initiation of cocaine self-administration in humans during
      abstinence: effects of dose, alternative reinforcement, and priming.
AB  - RATIONALE: Impaired ability to refrain from initiating cocaine-taking is a
      central feature of cocaine dependence and an important target for behavioral and
      pharmacological interventions. One potential trigger of cocaine-taking is
      exposure to cocaine (i.e. priming). OBJECTIVE: Here, we report a model of human
      cocaine self-administration that quantifies the ability to refrain from
      initiating cocaine self-administration during abstinence and after cocaine
      administration. METHODS: In a double-blind, within-subject, residential
      laboratory study, we assessed cocaine-taking as a function of the choice dose,
      priming dose, and the magnitude of alternative reinforcement. During each of 3
      weeks, cocaine-dependent volunteers participated in one sample and three choice
      sessions. During sample sessions, participants were administered the dose of
      cocaine (0, 15 or 30 mg/70 kg i.v.) available during subsequent choice sessions
      that week. During choice sessions, participants chose between cocaine and
      decreasing amounts of money ($19, $16, $13, $10, $7, $4, $1). A priming dose of
      cocaine (0, 15 or 30 mg/70 kg) was administered 30 min prior to the first choice
      trial during each of three choice sessions each week. RESULTS: Cocaine-taking was
      moderate, dose-dependent, and negatively related to the monetary alternative. An
      active priming injection of cocaine compared to placebo shifted choice to cocaine
      over money earlier in the session. CONCLUSIONS: A descending schedule of
      alternative reinforcement provided a measure of cocaine-taking during abstinence
      that was sensitive to cocaine choice dose, magnitude of alternative
      reinforcement, and priming. This procedure may be a useful tool for assessing
      potential therapies for cocaine dependence.

PMID- 14647957
TI  - Benzodiazepines and semantic memory: effects of lorazepam on the Moses illusion.
AB  - RATIONALE: When asked "How many animals of each kind did Moses take on the ark?",
      people fail to notice the distortion introduced by the impostor "Moses" and
      respond "two". It has been argued that the effect must be due to the existence of
      a partial-match process. In most situations, the form of a question is not likely
      to closely match the memory representation it queries. Thus, for the partial
      match hypothesis people ignore some semantic distortions. In the same vein, it
      has been shown that the benzodiazepine lorazepam drug induces some impairments of
      semantic memory as participants under lorazepam provide more incorrect recalls
      than placebo do with general information questions. OBJECTIVES: The aim of this
      study was to investigate the effects of the benzodiazepine lorazepam on the Moses
      illusion paradigm. METHOD: The effects of lorazepam (0.038 mg/kg) and of a
      placebo were investigated in 28 healthy volunteers. Twenty-two illusory questions
      were presented along with 72 normal general information questions. RESULTS:
      Lorazepam impaired the ability to detect the Moses illusion. Moreover, lorazepam
      participants appeared less biased to consider a question distorted than placebo
      participants. CONCLUSIONS: The temporary and reversible semantic memory
      impairments experienced by participants when falling into the Moses illusion are
      more frequent under lorazepam. The amnesic drug lorazepam may impair semantic
      processing as well as the strategic control of memory.

PMID- 14647958
TI  - Modulation of nerve growth factor and choline acetyltransferase expression in rat
      hippocampus after chronic exposure to haloperidol, risperidone, and olanzapine.
AB  - RATIONALE: Recently, we reported that compared to haloperidol, chronic exposure
      to either the risperidone (RISP) or olanzapine (OLZ) resulted in superior effects
      on spatial learning performance as well as the cholinergic neurons, although the
      mechanism for these effects was not addressed. OBJECTIVES: The objective of this
      study was to investigate one plausible mechanism whereby RISP and OLZ exert
      superior effects on cholinergic neurons, i.e. positive effects on nerve growth
      factor (NGF), which is known to regulate the brain cholinergic activity as well
      as cognitive function. Therefore, the effects of chronic exposure to HAL, RISP,
      or OLZ on the expression of NGF and choline acetyltransferase (ChAT) in the
      hippocampus (i.e. a brain area well known to be involved in cognitive function
      and known to receive major cholinergic projections from the medial septum) were
      compared. METHODS: Rats were treated with HAL (1 or 2 mg/kg per day), RISP (1.25
      or 2.5 mg/kg per day), or OLZ (5 or 10 mg/kg per day) for 45 days in drinking
      water. NGF and ChAT were measured by immunohistochemistry and NGF protein was
      also measured by an enzyme-linked ImmunoSorbent assay. RESULTS: Compared to
      controls, HAL exposure resulted in a marked reduction in NGF immunoreactivity in
      the hippocampal dentate gyrus (DG), CA1 and CA3 areas. In contrast, RISP did not
      alter, while OLZ significantly increased levels of NGF. These changes in NGF
      levels corresponded well with changes in ChAT immunoreactivity in the hippocampus
      and the medial septum. CONCLUSIONS: These preclinical data, combined with
      previously published behavioral results, support the premise that OLZ and RISP,
      in contrast to HAL, preserve cholinergic pathways and cognitive function via
      superior effects on NGF expression and are thus therapeutically superior for
      extended use.

PMID- 14647959
TI  - Aripiprazole (OPC-14597) fully substitutes for the 5-HT1A receptor agonist
      LY293284 in the drug discrimination assay in rats.
AB  - RATIONALE: Aripiprazole (OPC-14597) is a novel atypical antipsychotic drug with a
      low incidence of side effects. The therapeutic action of aripiprazole has been
      attributed to its unique agonist/antagonist effects at D(2) dopamine receptors;
      however, aripiprazole also has significant in vitro affinity at 5-HT(1A)
      receptors. OBJECTIVES: The 5-HT(1A) agonist property of aripiprazole has so far
      not been evaluated in any in vivo assay. METHODS: Thirteen male Sprague Dawley
      rats trained to discriminate the 5-HT(1A) agonist LY 293284 (75 nmol/kg) from
      saline, using a fixed ratio (FR) 50 schedule of food-reinforcement in a two-lever
      operant-conditioning task, were used to evaluate the behavioral effect of
      aripiprazole at 5-HT(1A) receptors. RESULTS: Aripiprazole fully mimicked LY
      293284 in a drug-discrimination assay with an ED(50) of 1.39 micromol/kg (0.62
      mg/kg). In combination tests, aripiprazole did not block the LY 293284 cue but at
      8.92 micromol/kg (4 mg/kg) significantly reduced the response rate by lowering
      the threshold for induction of the 5-HT syndrome produced by the training dose of
      LY 293284. Moreover, the selective 5HT(1A) receptor antagonist WAY 100635 was
      able to block the substitution of aripiprazole in LY-293284 trained rats.
      CONCLUSION: Although the efficacy of aripiprazole against the positive symptoms
      of schizophrenia may be related to its dopamine receptor interactions, it seems
      possible that its atypical profile may derive, at least in part, from its 5
      HT(1A) agonist effect, rather than from unusual D(2) receptor properties.

PMID- 14647960
TI  - Preliminary evidence of hippocampal dysfunction in adolescent MDMA ("ecstasy")
      users: possible relationship to neurotoxic effects.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a potent and
      selective serotonin neurotoxin whose use is growing among adolescents. Although
      cognitive deficits among adult MDMA users are well documented, little is known of
      the cognitive and brain functional sequelae of MDMA use during adolescence.
      OBJECTIVE: We tested for evidence of cognitive deficits and changes in brain
      function in a pilot sample of adolescent MDMA users, who were compared with
      adolescent non-users of MDMA. METHODS: Selective and divided attention and verbal
      working memory were examined in six adolescent MDMA users and six non-users of
      MDMA who were similar in age, gender, IQ, and other substance use. Brain function
      was assessed during performance of the working memory task using functional
      magnetic resonance imaging (fMRI). RESULTS: MDMA users had significantly
      prolonged reaction times during tests of selective and divided attention, and
      failed to deactivate the left hippocampus normally during high verbal working
      memory load. CONCLUSIONS: MDMA use in adolescence may be associated with
      cognitive impairments and dysfunction of inhibitory circuits within the
      hippocampus. Further work is urgently needed to delineate the developmental
      impact and long-term functional and clinical significance of MDMA use during
      adolescence.

PMID- 14647961
TI  - Sex differences in the reversal of fluoxetine-induced anorexia following raphe
      injections of 8-OH-DPAT.
AB  - RATIONALE AND OBJECTIVES: Serotonin (5-hydroxytryptamine, 5-HT) is widely
      distributed in the central nervous system and it is well established that this
      neurotransmitter plays an inhibitory role in the control of ingestive behavior.
      Administration of various 5-HT agonists and selective serotonin reuptake
      inhibitors, including fluoxetine (FLU), suppress food intake under free-feeding
      and food-restricted conditions. In contrast, activation of somatodendritc 5
      HT(1A) receptors in the raphe nuclei reduces forebrain 5-HT bioavailability and
      agonists of these receptors, including 8-hydroxy-2-(di-n-propylamino)tetralin (8
      OH-DPAT), reliably stimulate eating behavior. METHODS: In the present study male
      ( n=8 per group) and female ( n=8 per group) rats were pretreated with 8-OH-DPAT
      in an attempt to reverse FLU's inhibitory effect on feeding. 8-OH-DPAT was
      injected into either the dorsal or median raphe of male and female rats at doses
      of 0.1-0.4 nmol. FLU was then injected IP at a dose of 2 mg/kg. Both compounds
      were administered just prior to the onset of the dark cycle. Food intake was
      measured 2 h post-injection. Similar effects were also measured in female rats
      after ovariectomy. RESULTS AND CONCLUSIONS: FLU suppressed food intake comparably
      in male and female rats. Dorsal and median raphe injections of 8-OH-DPAT dose
      dependently reversed the anorectic effect of FLU in male rats. Higher doses of 8
      OH-DPAT completely antagonized this response. In female rats, however, 8-OH-DPAT
      pretreatment was largely ineffective except in ovariectomized females where
      results were similar to male rats. These findings suggest that male and female
      rats are differentially sensitive to the ability of 5-HT(1A) receptor agonists to
      antagonize the feeding suppressive action of FLU and imply a role for
      neuroendocrine mechanisms in enabling the somatodendritic autoreceptor to control
      serotonergic neurotransmission under these conditions.

PMID- 14647962
TI  - Changes in response to a dopamine receptor antagonist in rats with escalating
      cocaine intake.
AB  - RATIONALE AND OBJECTIVES: Prolonged access to cocaine self-administration (long
      access or LgA) produces an escalation in drug intake not observed with limited
      access to the drug (short access or ShA). The present study tested the hypothesis
      that escalating use of cocaine is associated with chronic alterations in dopamine
      neurotransmission. METHODS: After escalation of cocaine self-administration, ShA
      and LgA rats were challenged with different subcutaneous doses of cis
      flupenthixol (10-270 micro g/kg), a highly selective dopamine receptor
      antagonist. RESULTS: In both groups, increasing doses of cis-flupenthixol first
      produced an increase in the number of cocaine injections and then a dramatic
      suppression of behavior. This biphasic dose-effect function-which replicates
      previous findings from this laboratory-was shifted to the left in LgA rats
      relative to ShA rats, thereby decreasing the threshold dose at which behavior was
      completely suppressed. CONCLUSIONS: These data support the hypothesis that
      alterations in dopamine neurotransmission contribute to escalation of cocaine
      self-administration.

PMID- 14647963
TI  - Amisulpride is an "atypical" antipsychotic associated with low weight gain.
AB  - RATIONALE: It is possible that amisulpride, with its unique receptor binding
      profile, is not associated with significant weight gain, a serious side effect of
      most "atypical" antipsychotic drugs. While most "atypicals" have a high affinity
      for both dopamine and serotonin receptors, amisulpride has only dopamine receptor
      action. OBJECTIVES: To analyse the weight gain associated with amisulpride.
      METHODS: A pooled database of prospective randomised amisulpride studies was
      analysed. The mean weight gain after 10 weeks of treatment was estimated by
      regression analysis. RESULTS: Eleven studies with a total of 1422 patients were
      pooled, providing 1392 patients who were eligible for evaluation. In the main
      analysis of all effective doses (50-1200 mg/day) the mean weight gain associated
      with amisulpride at 10 weeks was 0.8 kg, 95% CI (0.48-1.18). Linear regression
      showed no dependence of weight gain on daily dose levels (P=0.7). When patients
      with mean daily doses below 400 mg/day were excluded in a sensitivity analysis,
      the mean weight gain at ten weeks was again 0.80 kg, 95% CI (0.47-1.16) with
      n=874. The mean weight gain at study endpoints in 1-year studies was 1.4 kg, 95%
      CI (0.85-1.90), n=548. CONCLUSION: Amisulpride is an atypical antipsychotic
      associated with low weight gain.

PMID- 14647964
TI  - Neuroleptic dysphoria: towards a new synthesis.
AB  - RATIONALE: Neuroleptic dysphoria (ND) is a subtle and under-recognized side
      effect of antipsychotic drugs. It is an all-inclusive descriptive phrase that
      encompasses a variety of unpleasant subjective changes in arousal, mood, thinking
      and motivation induced by neuroleptic drugs. Understanding this phenomenon has
      wide ranging clinical and research implications. OBJECTIVE: The present review
      examined the themes identified in the original studies from the neuroleptic era
      in the light of recent findings from neuroimaging research, cumulative experience
      with second generation antipsychotic drugs, and new concepts such as pleasure
      responsivity, hedonic regulation and subjective tolerability. METHODS: Empirical
      studies on neuroleptic drugs involving clinical populations treated for
      schizophrenia, Tourette's disorder and stuttering, studies performed on normal
      healthy volunteers and selected experimental studies in animals, are reviewed.
      RESULTS: Dysphoric responses occur early during treatment and typically manifest
      as a dislike towards medication (drug aversiveness). Dysphoria persisting over
      time, may lead to adverse clinical consequences such as treatment non-adherence,
      substance abuse, poor clinical outcome, increased suicidality and compromised
      quality of life. Interference with the physiological processes of hedonic
      capacity by the neuroleptics due to their dopaminergic blocking action in the
      prefrontal cortex and the shell of nucleus accumbens is the putative mediating
      mechanism underlying the occurrence of dysphoric responses. Second generation
      antipsychotic drugs with an atypical receptor blocking profile are less likely to
      elicit dysphoric responses. CONCLUSION: Viewing neuroleptic dysphoria within a
      broader spectrum of disorders of subjective tolerability and exploring its
      neurobiological mechanisms is relevant to addressing the nuances of antipsychotic
      therapy, and could help unravel the questions surrounding the pathophysiology of
      depression, substance abuse and other dysphoric clinical states.

PMID- 14647965
TI  - Effect of modafinil on fatigue, mood, and health-related quality of life in
      patients with narcolepsy.
AB  - INTRODUCTION: In addition to excessive sleepiness, patients with narcolepsy often
      have significant fatigue, depressed mood, and decreased quality of life.
      OBJECTIVE: To determine whether treatment with modafinil for excessive sleepiness
      improves fatigue, mood, and health-related quality of life (HRQOL) in patients
      with narcolepsy. MATERIALS AND METHODS: Outpatients with narcolepsy underwent a
      14-day washout of psychostimulants and then were enrolled in this 6-week, open
      label, multicenter study. Patients received modafinil starting at 200 mg once
      daily for week 1, and then 200 or 400 mg daily for weeks 2 through 6. Efficacy
      was evaluated using the Medical Outcomes Study 36-Item Short-Form Health Survey
      (SF-36) and the Profile of Mood States (POMS). Safety was assessed by monitoring
      adverse events (AE). RESULTS: At baseline, 151 patients had moderate to severe
      excessive sleepiness (mean Epworth Sleepiness Scale score=17.8+/-4.4). Most
      patients (> or =70% of 123 who completed the study) received 400 mg modafinil
      once daily during weeks 2 through 6. Modafinil significantly improved HRQOL,
      based on SF-36 measures of mental and physical component summary scores and
      subdomain scores of role-physical, social functioning, and vitality (each
      P<0.001). Modafinil treatment was also associated with significantly reduced
      fatigue and significantly improved vigor and cognition as assessed by the POMS
      (each P<0.001) from weeks 1 through 6. The most frequent AE with modafinil
      treatment were headache, nausea, and insomnia; most AE were mild or moderate in
      nature. Only seven patients (5%) withdrew from the study because of AE.
      CONCLUSION: In narcolepsy patients who were switched from psychostimulants,
      modafinil therapy improved HRQOL and subjective feelings of vigor and cognitive
      functioning and reduced fatigue.

PMID- 14647966
TI  - Stress-induced REM sleep increase is antagonized by naltrexone in rats.
AB  - RATIONALE: The expression of sleep is influenced by situations that take place
      during the preceding waking period, giving rise to different patterns of sleep
      architecture. Immobilization stress (IMB) induces an increase of both rapid eye
      movement (REM) and slow wave sleep (SWS). It has been suggested that these
      changes are mediated in part by noradrenaline and by the corticotrophin releasing
      factor. OBJECTIVE: To determine the participation of mu receptors in the stress
      induced increase of REM sleep using naltrexone (NTX). METHODS: Twelve adult male
      rats were implanted for sleep recordings. Subjects were recorded under control
      conditions as well as after: a) IMB stress (1 h); b) injection of NTX (1.5
      mg/kg); c) NTX plus IMB. To assess corticosterone levels, additional groups (
      n=5) were decapitated at 0, 1, 3 and 6 h after vehicle injection and after
      immobilization. Four groups were decapitated at 0, 1, 3, and 6 h after NTX plus
      IMB. Corticosterone plasma levels were determined by HPLC. RESULTS: IMB induces
      an increase in REM and SWS, and a decrease in wakefulness. Administration of NTX
      before IMB suppresses the effects of stress on sleep. NTX administration is
      innocuous in non-stressed animals. However, NTX administration does not prevent
      the rise of corticosterone normally observed after IMB stress. CONCLUSION: These
      data suggest that NTX prevents the effects of IMB stress on sleep by acting
      outside of the hypothalamic-pituitary-adrenal axis that partially mediates the
      stress response.

PMID- 14647967
TI  - Alcohol effects on human risk taking.
AB  - RATIONALE: Despite a well-established relationship between alcohol and risky
      behavior in the natural environment, laboratory investigations have not reliably
      shown acute alcohol effects on human risk-taking. OBJECTIVES: The present study
      was designed to demonstrate a dose-response relationship between acute alcohol
      administration and human risk taking. Further, this investigation sought to
      delineate behavioral mechanisms that may be involved in alcohol-induced changes
      in the probability of risky behavior. METHODS: Using a laboratory measure of risk
      taking designed to address acute drug effects, 16 adults were administered
      placebo, 0.2, 0.4, and 0.8 g/kg alcohol in a within-subject repeated measures
      experimental design. The risk-taking task presented subjects with a choice
      between two response options operationally defined as risky and non-risky. Data
      analyses examined: breath alcohol level (BAL), subjective effects, response
      rates, distribution of choices between the risky and non-risky option, and trial
      by-trial probabilities of making losing and winning risky responses. RESULTS: The
      alcohol administration produced the expected changes in BAL, subjective effects,
      and response rate. Alcohol dose-dependently increased selection of the risky
      response option, and at the 0.8 g/kg dose, increased the probability of making
      consecutive losing risky responses following a gain on the risky response option.
      CONCLUSIONS: Acute alcohol administration can produce measurable changes in human
      risk-taking under laboratory conditions. Shifts in trial-by-trial response
      probabilities suggest insensitivity to past rewards and more recent losses when
      intoxicated, an outcome consistent with previous studies. This shift in
      sensitivity to consequences is a possible mechanism in alcohol-induced changes in
      risk taking.

PMID- 14647968
TI  - Effects of dietary tryptophan variations on extracellular serotonin in the dorsal
      hippocampus of rats.
AB  - RATIONALE: There is evidence to suggest that the efficacy of selective serotonin
      reuptake inhibitors (SSRIs) in depression is dependent on the availability of
      serotonin (5-HT) in the brain. Moreover, there is circumstantial evidence
      suggesting that plasma tryptophan (TRP) levels can predict response to SSRIs.
      These findings suggest that dietary TRP variations may affect the efficacy of
      SSRI in major depression. OBJECTIVES: To study the neurochemical and behavioral
      effects of dietary TRP variations in rats. METHODS: In vivo microdialysis in the
      hippocampus was performed in conscious rats randomly assigned to receive a diet
      containing low, normal or high levels of TRP. Basal levels of 5-HT and 5-HIAA
      were measured using HPLC. Fenfluramine and fluvoxamine were infused locally to
      determine the effect of the diet on 5-HT availability and release. In a parallel
      group of rats, the differential reinforcement of low rate 72 s (DRL-72 s)
      schedule was used to assess the behavioral effects of the dietary manipulations.
      RESULTS: 5-HT and 5-HIAA levels were significantly decreased after TRP low diet
      and 5-HT, but not 5-HIAA, levels were significantly increased after TRP high
      diet. 5-HT release after fluvoxamine and fenfluramine was significantly
      diminished in rats on a TRP low diet, and significantly enhanced after
      fenfluramine in rats on a TRP high diet. DRL-72 performance in rats was decreased
      by a TRP low diet, whereas a TRP high diet increased DRL performance similar to
      fluvoxamine administration. CONCLUSION: The amount of 5-HT released after a 5-HT
      releasing agent and the effect of an SSRI on extracellular 5-HT are dependent on
      the nutritional availability of TRP. Moreover, increased availability of TRP
      affects behavior in a manner similar to SSRI administration. These findings
      suggest that nutritional factors have behavioral and neurochemical effects,
      relevant for the treatment of depression.

PMID- 14647969
TI  - Subjective effects of an initial dose of nicotine nasal spray predict treatment
      outcome.
AB  - RATIONALE: Nicotine nasal spray (NS) is recommended as one of five first-line
      smoking cessation products. A clinically convenient tool to identify smokers most
      likely to benefit from NS could assist healthcare practitioners in selecting the
      optimal treatment for individual patients. OBJECTIVES: To evaluate whether the
      subjective effects of an initial pre-treatment dose of NS predict 6 month
      abstinence rates following NS treatment for tobacco dependence. METHODS: One
      hundred and seventy-five smokers received an initial 1 mg pre-treatment dose of
      NS and completed a new measure of NS subjective effects (initial spray
      experience, ISE). This measure, together with demographic and smoking history
      variables, was examined as a predictor of 6-month point-prevalence (biochemically
      verified) abstinence rates. RESULTS: Factor analysis revealed positive and
      negative effects subscales of the ISE. Smokers with higher ratings of positive
      effects from the pre-treatment NS dose were significantly more likely to be
      abstinent at 6-month follow-up. These effects were partially mediated by
      reduction in urge to smoke. CONCLUSIONS: Pending additional validation in human
      laboratory and clinical studies, assessment of the acute positive subjective
      effects of initial NS delivery may be an efficient way to predict who will be
      successful with NS treatment for tobacco dependence.

PMID- 14647970
TI  - GABAA/alpha1 receptor agonists and antagonists: effects on species-typical and
      heightened aggressive behavior after alcohol self-administration in mice.
AB  - RATIONALE: The positive modulation of gamma-aminobutyric acid type-A (GABAA)
      receptors is a putative mechanism via which alcohol escalates aggressive
      behavior. Broad-spectrum benzodiazepine antagonists block alcohol-heightened
      aggression in rats and monkeys. However, the degree to which GABAA subunit
      composition plays a role in heightened aggressive behavior induced by self
      administration of a moderate alcohol dose remains unresolved. OBJECTIVE: Beta
      carboline-3-carboxylate-t-butyl ester (beta-CCt) and zolpidem act preferentially
      at GABAA receptors containing the alpha1 subunit as antagonist and agonist,
      respectively, and serve as useful tools to evaluate the role of GABAA receptor
      subtypes in self-administered alcohol on aggression. METHODS: Male resident mice,
      housed in breeding pairs, were conditioned to nose-poke in a removable panel in
      their home cage, with each fifth poke being reinforced by the delivery of 0.05 ml
      of 6% ethanol (EtOH). After consuming EtOH, the resident mice were given the
      antagonists beta-CCt and flumazenil or agonists zolpidem and triazolam, and then
      confronted an intruder male in their home cage for a 5-min period. RESULTS:
      Following self-administration of EtOH (1.0 g/kg, 1.7 g/kg), 14 of 37 resident
      mice displayed unusually large increases in the frequency of attack bites and
      sideways threats. Flumazenil or beta-CCt decreased alcohol-heightened and non
      heightened aggression in a dose-dependent manner. Administration of 3 mg/kg beta
      CCt lowered the aggression-heightening effects of 1 g/kg and 1.7 g/kg EtOH, but
      did not antagonize the sedative effects of 3.0 g/kg EtOH. Triazolam and zolpidem
      decreased alcohol-heightened and non-heightened aggressive behavior, and these
      antiaggressive effects were accompanied by reduced motor activity, indicating
      sedation. CONCLUSIONS: Benzodiazepine antagonists, particularly those acting
      preferentially at GABAA/alpha1 subunit-containing receptors, decrease alcohol
      heightened and species-typical aggressive behavior, but are ineffective in
      attenuating the sedative effects of alcohol.

PMID- 14647971
TI  - The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers.
AB  - RATIONALE: The use of herbal remedies, such as Ginkgo biloba and Ginseng, for
      improving cognitive performance has become increasingly popular during recent
      years. Several previous studies have indicated that administration of Ginkgo
      biloba and Ginseng may improve aspects of learning and memory in healthy
      volunteers. These results, however, are generally not supported by well
      controlled clinical studies. Also, positive results have often been reported from
      studies investigating effects related to short-term, chronic administration of
      the extract. Nonetheless, both Ginkgo biloba and Ginseng are marketed as having
      the capacity to enhance cognitive functions, such as memory and learning, in the
      long term. OBJECTIVE: This study aimed at investigating whether the use of Ginkgo
      biloba and Ginseng for a long period of time has positive effects on performance
      on learning and memory. METHODS: Community-dwelling volunteers ( n=3500) from The
      Betula prospective cohort study: memory, health, and aging were included in the
      study. RESULTS: It was found that the use of neither Ginkgo biloba ( n=40) nor
      Ginseng ( n=86) was associated with enhanced memory performance in any of the
      eight memory tests examined, relative to control groups either using or not using
      nutritional supplements. CONCLUSIONS: These findings indicate that use of Ginkgo
      biloba or Ginseng does not provide any quantifiable beneficial effects on memory
      performance in the long-term in healthy adult volunteers.

PMID- 14647975
TI  - Influence of alpha2-autoreceptor stimulation on the facilitation by angiotensin
      II and bradykinin of noradrenaline release.
AB  - The interaction between alpha(2)-autoreceptors and receptors for angiotensin II
      and bradykinin was studied in the heart of newborn rats. The tissues were labeled
      with [3H] noradrenaline and then superfused with cocaine-containing medium and
      stimulated electrically. Angiotensin II (30-1,000 nM) and bradykinin (10-300 nM)
      enhanced the evoked overflow of tritium, the maximum increase reaching 52.2 and
      72.8%, respectively. In the presence of the selective alpha(2)-adrenoceptor
      agonist UK-14,304, the maximal effect caused by angiotensin II and bradykinin was
      enhanced reaching 92.1 and 87.1% for angiotensin II and bradykinin, respectively.
      On the contrary, in the presence of chelerythrine (a protein kinase C blocker),
      not only the increment in facilitation by UK-14,304, but to some extent also the
      basal facilitation caused by angiotensin II and bradykinin were markedly reduced
      (to 17.3 and 43.2%, respectively). We conclude that: 1. The stimulation of alpha2
      autoreceptors enhances the facilitatory responses caused by angiotensin II and
      bradykinin, confirming that an ongoing alpha2-autoinhibition is required for the
      facilitatory influence of the peptides. 2. Protein kinase C is involved in the
      enhancement by angiotensin II and bradykinin of electrically-evoked release of
      noradrenaline from the nerve terminals.

PMID- 14647976
TI  - DNA adduct formation and physiological effects from crude oil distillate and its
      derived base oil in isolated, perfused rat liver.
AB  - A distillate, D431, originating from Venezuelan heavy crude oil and a severely
      hydro-treated base oil, BO100, derived from this distillate, were tested for DNA
      adduct formation capacities and overall impact on liver functions. D431 had
      earlier showed DNA adduct formation in vitro but not in vivo in the rat. In this
      study, isolated rat liver perfusions were performed to elucidate whether the lack
      of DNA adducts in vivo was because of lack of uptake or metabolism. The oils were
      extracted with dimethyl sulfoxide and the extracts added to the perfusion system.
      Bile production, lactate metabolism and perfusate flow through the organ, which
      are parameters that reveal the condition of the liver, were continuously
      monitored. Samples of liver were collected once every hour during perfusion for
      DNA adduct analysis with (32)P-HPLC. The results for the distillate D431 showed
      that the production of bile and metabolism of lactate decreased while DNA adduct
      formation increased with time. The DNA adduct pattern formed in the D431-treated
      livers was similar to that found earlier in in vitro studies performed on calf
      thymus DNA (CT-DNA). In the case of DNA adduct formation, virtually no difference
      with dose was seen, suggesting that perhaps a point of saturation of, for
      instance, enzymatic systems was reached. The results for base oil BO100 showed no
      significant difference regarding bile production, lactate metabolism and DNA
      adduct formation when compared with the control, indicating no toxic or genotoxic
      activity.

PMID- 14647974
TI  - Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by
      influx of extracellular Ca2+ and partly by release of intracellular stores.
AB  - Green tea has been receiving considerable attention as a possible preventive
      agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate
      (EGCG) is a major polyphenol component of green tea. Using digital calcium
      imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG
      increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87
      cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG
      induced [Ca2+]i increases were reduced to 20.9% of control by removal of
      extracellular Ca2+. The increases were also inhibited markedly by treatment with
      the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1
      mM) for 5 min. The increases were not significantly inhibited by treatment for 10
      min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the
      inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also
      significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min
      with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the
      increases significantly, while the tyrosine kinase inhibitor genistein (30 micro
      M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC
      activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic
      acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG
      induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but
      indomethacin (100 micro M) did not affect the increases. Collectively, these data
      suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by
      eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular
      Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly
      through channels sensitive to diphenylamine-2-carboxylate derivatives.

PMID- 14647973
TI  - Beta-adrenoceptor polymorphisms.
AB  - There can be no doubt that beta(1)-, beta(2)- and beta(3)-adrenoceptor genes have
      genetic polymorphisms. Two single nucleotide polymorphisms have been described
      for the beta(1)- (Ser49Gly; Gly389Arg), three for the beta(2)- (Arg16Gly;
      Gln27Glu; Thr164Ile) and one for the beta(3)-adrenoceptor subtype (Trp64Arg) that
      might be of functional importance. The possibility that changes in expression or
      properties of the beta-adrenoceptors due to single nucleotide polymorphisms might
      have phenotypic consequences influencing their cardiovascular or metabolic
      function or may contribute to the pathophysiology of several disorders like
      hypertension, congestive heart failure, asthma or obesity is an idea that has
      attracted much interest during the last 10 years. At present, it appears that
      these beta-adrenoceptor polymorphisms are very likely not disease-causing genes,
      but might be risk factors, might modify disease and/or might influence
      progression of disease. The aim of this review is to provide an overview of the
      functional consequences of such beta-adrenoceptor polymorphisms in vitro, ex vivo
      and in vivo.

PMID- 14647977
TI  - Free radical generating agents lead to the rapid progression of benign skin
      tumors to carcinoma in iron-overloaded mice.
AB  - Free radical generating compounds have been shown to enhance the malignant
      conversion of papillomas to carcinomas in mouse skin, and iron has been shown to
      participate in free radical generating reactions. In the present study, we
      investigated whether iron can play a role in the malignant conversion of
      papillomas to carcinomas. Skin tumors were chemically induced in female Swiss
      albino mice using a standard two-stage initiation-promotion protocol. Topical
      application of 12- O-tetradecanoyl phorbol 13-acetate (TPA), benzoyl peroxide
      (BPO), H(2)O(2) and cumene hydroperoxide (COOH) to these tumor-bearing mice
      increased the rate of malignant conversion. To evaluate the effect of iron
      overload on the conversion of benign skin papillomas to carcinomas, the animals
      were pre-treated with 1.0 mg Fe per mouse for 15 days before they received TPA or
      free radical generating compounds. The number of carcinomas and the percent
      incidence of carcinomas were recorded weekly. The rate of malignant conversion
      was higher in iron-overloaded mice as compared with non-iron-overloaded mice. The
      ability of iron-overload in enhancing the malignant conversion was in the order
      TPA<BPO<H(2)O(2)<COOH. Iron was the most effective in enhancing COOH-mediated
      malignant transformation. Inorganic peroxide (H(2)O(2))-mediated malignant
      transformation was also enhanced effectively by iron. This may be because a
      combination of iron accessibility and H(2)O(2) results in the formation of the
      very reactive hydroxyl radical via the Fenton reaction, which can cause DNA
      damage. Besides this, the cutaneous iron levels were also higher in iron
      overloaded mice as compared with non-iron-overloaded mice. Histopathological
      sections of tumors also showed a higher degree of keratinization and pearl
      formation in iron-overloaded animals. Thus, we observe that in iron-overloaded
      animals, free radical generating agents bring about the rapid progression of
      benign mouse skin papillomas to carcinomas.

PMID- 14647979
TI  - Production of plantaricin NC8 by Lactobacillus plantarum NC8 is induced in the
      presence of different types of gram-positive bacteria.
AB  - Lactobacillus plantarum NC8 was shown to produce plantaricin NC8 (PLNC8), a
      recently purified and genetically characterized inducible class IIb bacteriocin,
      only when it was co-cultured with other gram-positive bacteria. Among 82 strains
      belonging to the genera Bacillus, Enterococcus, Lactobacillus, Lactococcus,
      Leuconostoc, Listeria, Pediococcus, Staphylococcus, and Streptococcus, 41 were
      shown to induce PLNC8 production in L. plantarum NC8. There was apparently no
      relationship between the sensitivity of the strains and their ability to induce
      the bacteriocin, indicating that the inducer and sensitive phenotypes may not be
      linked. In some instances, induction was promoted by both living and heat-killed
      cells of the inducing bacteria. However, no PLNC8-inducing activity was found in
      the respective cell-free, pure culture supernatants. Inducer strains also
      promoted the production of a PLNC8-autoinducing activity by L. plantarum NC8,
      which was found only in the cell-free co-culture supernatants showing inhibitory
      activity. This PLNC8-autoinducing activity was diffusible, heat resistant, and of
      a proteinaceous nature, and was different from the bacteriocin itself. Taken
      together, the results suggest that the presence of specific gram-positive
      bacteria acts as an environmental stimulus activating both PLNC8 production by L.
      plantarum NC8 and a PLNC8-autoinducing activity, which in turn triggers or
      maintains bacteriocin production in the absence of inducing cells.

PMID- 14647978
TI  - Reactivation and aging kinetics of human acetylcholinesterase inhibited by
      organophosphonylcholines.
AB  - A great number of structurally different organophosphorus compounds (OPs) was
      synthesized in the past decades to be used as pesticides or chemical warfare
      agents. Methyl-fluorophosphonylcholines were found to be highly toxic OPs and the
      acetylcholinesterase (AChE) reactivator pralidoxime was shown to be unable to
      reactivate inhibited AChE. In the course of the development of more effective
      AChE reactivators, we have determined the reactivation rate constants of various
      oximes with human AChE inhibited by methylfluorophosphonylcholine (MFPCh),
      methylfluoro-beta-phosphonylcholine (MFP beta Ch) and
      methylfluorophosphonylhomocholine (MFPhCh). In addition, we investigated the
      potential influence of aging phenomena on the oxime efficacy. Human AChE
      inhibited by MFPCh, MFP beta Ch or MFPhCh was extremely resistant towards
      reactivation by oximes. Nevertheless, the newer compounds, HLo 7 and HI 6, were
      substantially more potent reactivators than obidoxime and pralidoxime. The low
      oxime efficacy was not due to rapid aging since no decrease in reactivatability
      was found over 96 h at 37 degrees C. Within this period a substantial spontaneous
      reactivation was observed, with MFPCh >MFP beta Ch >MFPhCh, which did not follow
      pseudo-first-order kinetics. In conclusion, the unexpected results, i.e., high
      resistance of inhibited AChE towards oxime reactivation and aging, and much lower
      resistance towards spontaneous reactivation, calls for further experiments at a
      molecular level for a better understanding of the interactions among AChE, its
      inhibitors and reactivators.

PMID- 14647980
TI  - Identification by gene deletion analysis of barB as a negative regulator
      controlling an early process of virginiamycin biosynthesis in Streptomyces
      virginiae.
AB  - The Streptomyces virginiae gamma-butyrolactone autoregulator virginiae butanolide
      is a low-molecular-weight Streptomyces hormone eliciting virginiamycin
      biosynthesis through its binding to the specific receptor protein, BarA.
      Immediately downstream of barA lies barB, the transcription of which is tightly
      repressed by BarA in the absence of virginiae butanolide and derepressed in its
      presence. Thus, BarB is next to BarA on the virginiae butanolide-BarA signaling
      cascade. An in-frame 279-bp deletion was introduced into the barB allele, which
      rendered it inactive by eliminating the majority of the coding region, including
      the helix-turn-helix DNA-binding motif. No significant change was observed with
      the Delta barB mutant with respect to the timing or amount of virginiae
      butanolide production, or the morphological differentiation on solid media,
      indicating that barB neither participates in virginiae butanolide biosynthesis
      nor in cytodifferentiation. In contrast, analysis of virginiamycin production in
      the Delta barB mutant revealed that production of both virginiamycin M(1) and
      virginiamycin S occurred immediately after virginiae butanolide production, 2-3 h
      earlier than in the wild-type strain, indicating that BarB participates in the
      temporal retardation of virginiamycin production after virginiae butanolide
      inactivates the repressor function of BarA. RT-PCR analysis of the transcription
      of several genes surrounding barA-barB by the Delta barB mutant indicated that
      BarB plays a negative regulatory role, directly or indirectly, in the
      transcription of barZ, vmsR, and orf5 located upstream of barB.

PMID- 14647981
TI  - Optimisation of brain SPET and portability of normal databases.
AB  - Use of a normal database in quantitative regional analysis of brain single-photon
      emission tomography (SPET) facilitates the detection of functional defects in
      individual or group studies by accounting for inter-subject variability.
      Different reconstruction methods and suboptimal attenuation and scatter
      correction methods can introduce additional variance that will adversely affect
      such analysis. Similarly, processing differences across different instruments
      and/or institutions may invalidate the use of external normal databases. The
      object of this study was to minimise additional variance by comparing
      reconstructions of a physical phantom with its numerical template so as to
      optimise processing parameters. Age- and gender-matched normal scans acquired on
      two different systems were compared using SPM99 after processing with both
      standard and optimised parameters. For three SPET systems we have optimised
      parameters for attenuation correction, lower window scatter subtraction,
      reconstructed pixel size and fanbeam focal length for both filtered back
      projection (FBP) and iterative (OSEM) reconstruction. Both attenuation and
      scatter correction improved accuracy for all systems. For single-iteration Chang
      attenuation correction the optimum attenuation coefficient (mu) was 0.45-0.85 of
      the narrow beam value (Nmu) before, and 0.75-0.85 Nmu after, scatter subtraction.
      For accurately modelled OSEM attenuation correction, optimum mu was 0.6-0.9 Nmu
      before and 0.9-1.1 Nmu after scatter subtraction. FBP appeared to change in-plane
      voxel dimensions by about 2% and this was confirmed by line phantom measurements.
      Improvement in accuracy with scatter subtraction was most marked for the highest
      spatial resolution system. Optimised processing reduced but did not remove highly
      significant regional differences between normal databases acquired on two
      different SPET systems.

PMID- 14647982
TI  - Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent.
AB  - In spite of recent advances in bone cellular and molecular biology, there is
      still a poor correlation between these parameters and data obtained from bone
      scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc
      BPs) have long been recognised as bone-seeking agents with an affinity for areas
      of active mineralisation. However, during clinical trials with a pH-sensitive
      tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid
      [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies
      (bone metastases, Paget's diseases) and lacked accumulation in normal mature
      bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular
      level was considered necessary. Moreover, to learn more about the role of Tc bone
      agents, acid-base regulation by bone tissue or cells was studied. First,
      biological parameters in body fluid were measured under systemic acidosis,
      induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)
      bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a
      conventional Tc-BP agent were carried out. The effect of glucose-mediated
      acidification on the skeletal distribution of the Tc agents in the mice provided
      valuable hints regarding the differential mediation of bone cells in skeletal
      tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and
      osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc
      BP was screened under diverse acidification conditions. Moreover, studies were
      also carried out on acid-base parameters related to the cellular uptake
      mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the
      osteoclastic system was detected, and use of Tc(V)-DMS in the differential
      detection of osteoblastic and osteoclastic metastases is discussed.

PMID- 14647983
TI  - Application of statistical parametric mapping to SPET in the assessment of
      intractable childhood epilepsy.
AB  - Statistical parametric mapping (SPM) quantification and analysis has been
      successfully applied to functional imaging studies of partial epilepsy syndromes
      in adults. The present study evaluated whether localisation of the epileptogenic
      zone (determined by SPM) improves upon visually examined single-photon emission
      tomography (SPET) imaging in presurgical assessment of children with temporal
      lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). The patient sample consisted
      of 24 children (15 males) aged 2.1-17.8 years (9.8+/-4.3 years; mean+/-SD) with
      intractable TLE or FLE. SPET imaging was acquired routinely in presurgical
      evaluation. All patient images were transformed into the standard stereotactic
      space of the adult SPM SPET template prior to SPM statistical analysis.
      Individual patient images were contrasted with an adult control group of 22
      healthy adult females. Resultant statistical parametric maps were rendered over
      the SPM canonical magnetic resonance imaging (MRI). Two corresponding sets of
      ictal and interictal SPM and SPET images were then generated for each patient.
      Experienced clinicians independently reviewed the image sets, blinded to clinical
      details. Concordance of the reports between SPM and SPET images, syndrome
      classification and MRI abnormality was studied. A fair level of inter-rater
      reliability (kappa=0.73) was evident for SPM localisation. SPM was concordant
      with SPET in 71% of all patients, the majority of the discordance being from the
      FLE group. SPM and SPET localisation were concordant with epilepsy syndrome in
      80% of the TLE cases. Concordant localisation to syndrome was worse for both SPM
      (33%) and SPET (44%) in the FLE group. Data from a small sample of patients with
      varied focal structural pathologies suggested that SPM performed poorly relative
      to SPET in these cases. Concordance of SPM and SPET with syndrome was lower in
      patients younger than 6 years than in those aged 6 years and above. SPM is
      effective in localising the potential epileptogenic zone but does not provide
      additional benefit beyond SPET in presurgical assessment of children with
      intractable epilepsy. The impact of different pathologies on the efficacy of SPM
      warrants further study.

PMID- 14647984
TI  - Do we need randomised trials to evaluate diagnostic procedures? For.

PMID- 14647985
TI  - Optimised nuclear medicine method for tumour marking and sentinel node detection
      in occult primary breast lesions.
AB  - The aim of this study was to evaluate the feasibility of sentinel node (SN)
      biopsy in occult breast lesions with different radiopharmaceuticals and to
      establish the optimal lymphoscintigraphic method to detect both occult lesions
      and SNs (SNOLL: sentinel node and occult lesion localisation). Two hundred and
      twenty-seven consecutive patients suspected to have clinically occult breast
      carcinoma were enrolled in the study. In addition to the radioguided occult
      lesion localisation (ROLL) procedure, using macroaggregates of technetium-99m
      labelled human serum albumin (MAA) injected directly into the lesion,
      lymphoscintigraphy was performed with nanocolloids (NC) injected in a peritumoral
      (group I) or a subdermal site (group II). In group III, a sole injection of NC
      was done into the lesion in order to perform both ROLL and SNOLL. Overall,
      axillary SNs were identified in 205 of the 227 patients (90.3%). In 12/62 (19.4%)
      patients of group I and 9/79 (11.4%) patients of group III, radioactive nodes
      were not visualised, whereas SNs were successfully localised in 85 of 86 patients
      of group II ( P<0.001). Pathological findings revealed breast carcinoma in
      148/227 patients (65.2%) and benign lesions in 79 (34.8%). A total of 131
      axillary SNs were removed in 118 patients with breast carcinoma; intraoperative
      examination of the SNs revealed metastatic involvement in 16 out of 96 cases of
      invasive carcinoma (16.7%). It is concluded that the combination of the ROLL
      procedure with direct injection of MAA into the lesion and lymphoscintigraphy
      performed with subdermal injection of radiocolloids represents the method of
      choice for accurate localisation of both non-palpable lesions and SNs.

PMID- 14647986
TI  - Comparison of sestamibi, thallium, echocardiography and PET for the detection of
      hibernating myocardium.
AB  - The detection of hibernating myocardium is important because revascularisation
      results in improved function and prognosis in patients with hibernation but not
      in those with non-viable myocardium. The primary aim of this study was to compare
      the diagnostic accuracy of four techniques with respect to hibernation in the
      same study population with 6-12 months of follow-up. Twenty-five males underwent
      rest-stress sestamibi and delayed (>18 h) thallium scintigraphy, high-dose
      dobutamine stress echocardiography and nitrogen-13 ammonia/fluorine-18
      fluorodeoxyglucose (NH(3)/FDG) positron emission tomography (PET). The pre
      operative ejection fraction was 36.2% (+/-7.3%). Follow-up was 8.1 (+/-2.8)
      months. Using postoperative improvement in wall motion on echocardiography as the
      gold standard, 6/34 dysfunctional vascular territories were hibernating. The mean
      uptake of all tracers was significantly higher in hibernating than in non-viable
      territories ( P<0.05). Normal perfusion or mismatch on PET (FDG>NH(3) uptake) and
      the pattern of response to dobutamine on echocardiography were also predictive of
      recovery ( P<0.001 and P=0.02 respectively). Univariate logistic regression
      identified sestamibi, ammonia and FDG as independent predictors of hibernation.
      FDG-PET was, however, the only independent predictor using multivariate analysis.
      The nuclear techniques had high negative predictive values (NPV) of >or=95% but
      lower positive predictive values (PPV) of 45%-75% as compared with
      echocardiography, which had an NPV of 87% and a PPV of 100%. PET was the most
      powerful predictor of hibernation although the combination of a technique with a
      high PPV (echocardiography) and a high NPV (PET or sestamibi) may represent the
      optimal clinical choice.

PMID- 14647988
TI  - FDG-PET/CT in re-staging of patients with lymphoma.
AB  - The aim of this study was to evaluate the clinical significance of combined
      fluorine-18 fluorodeoxyglucose positron emission tomography and computed
      tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT
      staging results with those of FDG-PET and CT alone. Twenty-seven patients were
      studied. Each patient had clinical follow-up for >12 months and entered complete
      follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT
      alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93%
      for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for
      regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT
      imaging is superior to CT alone ( P=0.02) and has additional benefit over FDG-PET
      alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging
      is accurate in re-staging lymphoma and offers advantages over separate FDG-PET
      and CT imaging.

PMID- 14647989
TI  - Fibrous dysplasia with cartilaginous differentiation ("fibrocartilaginous
      dysplasia"): a review, with an illustrative case followed for 18 years.
AB  - A 21-year-old man with an 18-year history of progressive, and deforming,
      monomelic fibrous dysplasia with massive cartilaginous differentiation
      (fibrocartilaginous dysplasia) is described. A review is made of all prior
      reported examples of this entity in the English language medical literature. The
      radiologic and histologic differential diagnoses are described, distinguishing
      the lesion from chondrosarcoma and from fibrocartilaginous mesenchymoma.

PMID- 14647990
TI  - Biotransformation of halophenols using crude cell extracts of Pseudomonas putida
      F6.
AB  - Crude cell extracts of Pseudomonas putida F6 transformed 4-substituted fluoro-,
      chloro-, bromo- and iodo-phenol without the exogenous addition of cofactors. The
      rate of substrate consumption decreased with increasing substituent size
      (F>Cl>Br>I). Biotransformations resulted in greater than 95% utilisation of the
      halogenated substrate. Product accumulation was observed in incubations with 4
      chloro, 4-bromo- and 4-iodo-phenol. These products were identified as the
      corresponding 4-substituted catechols. Transformation of 4-fluorophenol did not
      result in the accumulation of the corresponding catechol; however, manipulation
      of the reaction conditions by incorporation of ascorbic acid culminated in the
      formation of 4-fluorocatechol. Cell extracts of P. putida F6 also showed activity
      towards a 3-substituted phenol, namely 3-fluorophenol, resulting in the formation
      of a single product, 4-fluorocatechol.

PMID- 14647991
TI  - The EGF-TM7 family: a postgenomic view.
AB  - With the human and mouse genome projects now completed, the receptor repertoire
      of mammalian cells has finally been elucidated. The EGF-TM7 receptors are a
      family of class B seven-span transmembrane (TM7) receptors predominantly
      expressed by cells of the immune system. Within the large TM7 superfamily, the
      molecular structure and ligand-binding properties of EGF-TM7 receptors are
      unique. Derived from the processing of a single polypeptide, they are expressed
      at the cell surface as heterodimers consisting of a large extracellular region
      associated with a TM7 moiety. Through a variable number of N-terminal epidermal
      growth factor (EGF)-like domains, EGF-TM7 receptors interact with cellular
      ligands such as CD55 and chondroitin sulfate. Recent in vivo studies demonstrate
      a role of the EGF-TM7 receptor CD97 in leukocyte migration. The different number
      of EGF-TM7 genes in man compared with mice, the chimeric nature of EMR2 and the
      inactivation of human EMR4 point toward a still-evolving receptor family. Here we
      discuss the currently available information on this intriguing receptor family.

PMID- 14647992
TI  - Identification of the rat IgA Fc receptor encoded in the leukocyte receptor
      complex.
AB  - Human FcalphaRI (CD89) is a myeloid-specific IgA Fc receptor encoded in the
      leukocyte receptor complex. Thus far, no gene coding for FcalphaRI has been
      identified in mice. Here, we show that, unlike mice, rats have the gene ( Fcar)
      coding for FcalphaRI. The rat Fcar gene has an exon-intron structure essentially
      identical to that of the human counterpart and is encoded in the leukocyte
      receptor complex on Chromosome 1. Southern blot analysis using the rat Fcar as a
      probe revealed hybridizing bands in Chinese and Syrian hamsters and gerbils, but
      not in mice, indicating that Fcar was lost in the lineage leading to mice after
      the divergence of rats and mice. Identification of FcalphaRI in rats should
      facilitate the elucidation of the in vivo role of this receptor.

PMID- 14647994
TI  - Spontaneous occlusion of post-traumatic splenic pseudoaneurysm: report of two
      cases in children.
AB  - Conservative therapy for splenic injuries is widely advocated. The advantages of
      conservative therapy for splenic injuries include the preservation of splenic
      immune function, prevention of overwhelming post-splenectomy sepsis, and
      avoidance of laparotomy and its associated early and late complications.
      Pseudoaneurysms of the splenic artery branch are encountered because of the
      prevalence of conservative management and widespread use of imaging techniques in
      the follow-up of these cases. We report two cases of post-traumatic splenic
      pseudoaneurysm in children which thrombosed spontaneously, one during the
      diagnostic angiogram examination and another on follow-up studies.

PMID- 14647993
TI  - Farnesylated peptides in model membranes: a biophysical investigation.
AB  - Protein prenylation plays an important role in signal transduction, protein
      protein interactions, and the localization and association of proteins with
      membranes. Using three different techniques, this study physically characterizes
      the interactions between model dimyristoylphosphatidylcholine membranes and a
      series of farnesylated peptides. Magic angle spinning nuclear Overhauser
      enhancement spectroscopy and differential scanning calorimetry reveal that both
      charged [Ac-Asn-Lys-Asn-Cys-(farnesyl)-OMe and Ac-Asn-Lys-Asn-Cys-(farnesyl)
      NH(2)] and uncharged [Ac-Cys-(farnesyl)-OMe and farnesol] species partition into
      dimyristoylphosphatidylcholine bilayers. Calorimetry and vesicle fluctuation
      analysis of giant unilamellar vesicles show that the charged peptides modestly
      decrease the main gel-fluid phase transition and markedly increase the bending
      rigidity of large unilamellar vesicles. Uncharged species, on the other hand,
      dramatically decrease the main phase transition and modestly decrease the bending
      rigidity. No difference with carboxyl methylation is detected.

PMID- 14647995
TI  - Cerebral metastasis proven 1 year after an embolic cerebral infarct from
      pleuropulmonary blastoma.

PMID- 14647996
TI  - Stroke is an important paediatric illness.

PMID- 14647997
TI  - The paediatric overview.
AB  - Stroke in children, both ischaemic and haemorrhagic, is increasingly recognised
      as an important paediatric illness. This review looks at the wide number of
      causes, highlighting the fact that often no single factor is causative on its
      own. There has been an increased recognition worldwide of the importance of
      sickle cell disease and of the importance of venous sinus thrombosis. Radiology
      is mandatory in diagnosis and management. Unfortunately, it is not always
      possible to extrapolate experience from adult stroke in terms of management of
      these children, and further detailed trials are necessary to understand the
      natural history, outcome and best forms of management.

PMID- 14647998
TI  - Idiopathic intraparenchymal hematoma of the liver in a neonate.
AB  - Hepatic hematomas in newborn infants are not frequently detected clinically, but
      are often found at perinatal autopsies. These hematomas of the liver are usually
      subcapsular in location. A variety of etiologies for such hematomas has been
      implicated, such as trauma, sepsis, and coagulopathies. We present a neonate who
      presented with jaundice and abdominal distention. Initial imaging studies
      revealed a large intraparenchymal lesion of the liver, which was at first thought
      to be suspicious for neoplasm; however, MRI showed the lesion to be hemorrhagic
      and follow-up sonographic studies showed total resolution of this lesion,
      compatible with hematoma. The intraparenchymal location and the idiopathic nature
      of this lesion distinguish this case from others previously reported.

PMID- 14647999
TI  - Evolution of heart rate control after transplantation: conduction versus
      autonomic innervation.
AB  - In cardiac transplantation, the donor organ is not initially innervated and
      demonstrates decreased heart rate variability (HRV). However, HRV may improve
      after several months. The mechanism for HRV improvement has not been elucidated;
      autonomic "reinnervation" of the donor heart has been proposed. The role of
      atrioatrial conduction from recipient to donor organ has not been evaluated. We
      prospectively evaluated cardiac transplant patients with a limited
      electrophysiology study at the time of their surveillance biopsies. Recordings
      were made of recipient and donor signals, observing conduction properties between
      recipient and donor atria. Holter recordings were analyzed and HRV was determined
      using spectral analysis techniques, recording mean RR interval, low-frequency
      power (LF), high-frequency power (HF), and the LF/HF ratio. These were compared
      to published norms. From November 1999 to May 2000, 21 patients (6 female) who
      underwent cardiac transplantation participated at a median age of 101 months
      (range, 4.1-217 months). Time posttransplant ranged from 26 days to 71 months.
      Holter data were available for 20 patients and demonstrated dissociated P waves
      in 13 (65%). The mean heart rate on Holter was 111 beats per minute (bpm) (range,
      85-161 bpm). We were able to record distinct recipient atrial signals in 16 of 21
      (76%) patients. The average recipient tissue heart rate was 55% that of the donor
      heart rate. We documented atrioatrial association in only 1 patient. HRV did not
      reach normal values for most patients and did not increase with time
      posttransplantation. The LF values were in the normal range for most patients,
      whereas 3 patients had normal HF values and 2 patients had values just below
      normal. Recipients of heart transplantation have a predominantly sympathetic
      influence of HRV. These preliminary data suggest that atrioatrial conduction does
      not play a role in reestablishing normal heart rate control following pediatric
      cardiac transplantation.

PMID- 14648000
TI  - Myocardial contractility in premature neonates with and without patent ductus
      arteriosus.
AB  - Controversy exists as to whether a hemodynamically significant left-to-right
      shunt due to a patent ductus arteriosus (PDA) affects ventricular contractility.
      Load-dependent indices such as ejection fraction and shortening fraction have
      traditionally been used to assess contractility, but the relationship between the
      rate-corrected velocity of fiber shortening (MVCFc) and wall stress may be more
      suitable, as it is a preload-independent, afterload-adjusted method of assessing
      ventricular contractility. Age-related differences have been established for
      these variables in normal adults and children and it has been recommended for use
      in the premature neonate. The study was performed to assess left ventricular
      contractility in premature neonates with a significant left-to-right shunt due to
      a PDA. Using echocardiography, we measured the relationship of MVCFc to stress at
      peak systole (SPS) in two groups of premature infants. Group 1 consisted of 15
      controls (680-1495 g, 25-32 weeks' gestation), and Group 2 of 15 neonates with
      hemodynamically significant PDA (840-1635 g, 26-33 weeks' gestation). In both
      groups, MVCFc was linearly and inversely related to SPS ( p < 0.001). The
      regression equations were as follows: Group 1, MVCFc = -0.0153SPS + 1.70 ( R(2) =
      0.68); and Group 2, MVCF = - 0.019SPS + 1.89 ( R(2) = 0.76). There was no
      significant difference in the relationship between the two groups, but their
      slopes were significantly steeper and had a higher Y-intercept than the
      relationship we previously reported for older children. This preliminary study
      establishes the normal MVCFc/SPS relationship in the premature neonate (25-33
      weeks' gestation) and suggests that premature infants function at a higher
      resting contractile state than older children. A hemodynamically significant PDA
      has no effect on contractility. These data will be useful in assessing left
      ventricular contractility in premature neonates with other types of ventricular
      loading and noncardiac stress.

PMID- 14648001
TI  - Tei index determined by tissue Doppler imaging in patients with pulmonary
      regurgitation after repair of tetralogy of Fallot.
AB  - The myocardial performance index (Tei index) determined by the pulsed Doppler
      method is a simple and noninvasive measurement for assessing global right
      ventricular (RV) function. This index can also be obtained by tissue Doppler
      imaging (TDI). The effects of significant pulmonary regurgitation (PR) on the
      determination of the Tei index by these two methods have not been investigated.
      We examined 15 patients (6.3 +/- 2.2 years) with significant PR after repair of
      tetralogy of Fallot (TOF) and 24 age-matched healthy children. Myocardial wall
      motion velocities at the tricuspid annulus were assessed during systole (Sa),
      early diastole (Ea), and late diastole (Aa) from a four-chamber view. Pulsed
      Doppler-Tei index and TDI-Tei index were measured as reported previously. The Tei
      index obtained by the pulsed Doppler method in TOF patients did not differ from
      that in normal children (0.30 +/- 0. 12 vs 0.32 +/- 0.07, p = not significant).
      TDI showed that TOF patients had significantly decreased Ea, Aa, and Sa
      velocities compared to those of normal children. Both isovolumic contraction time
      and isovolumic relaxation time in TOF patients were significantly longer than
      those in normal children (88 +/- 18 vs 62 +/- 23 msec and 46 +/- 11 vs 21 +/- 12
      msec, respectively; p < 0.0001), although the duration of Sa did not differ
      between the two groups. Consequently, the Tei index as measured by TDI was
      significantly greater in TOF patients than in normal children (0.48 +/- 0.07 vs
      0.30 +/- 0.07, p < 0.0001). The Tei index measured by the pulsed Doppler method
      is limited in its ability to assess RV function in patients with significant PR.
      However, the Tei index determined by TDI is a sensitive indicator of RV function
      in these patients, and it appears to be a promising new means of assessing global
      RV function in patients with significant PR.

PMID- 14648003
TI  - Congenital heart disease in infants of diabetic mothers: echocardiographic study.
AB  - Our objective was to study neonates born to insulin-dependent diabetes mellitus
      (IDDM) mothers to detect the spectrum of congenital heart disease (CHD). Between
      July 2000 and June 2001, a prospective study of 100 consecutive infants of
      diabetic mothers (IDMs) at King Khalid University Hospital in Riyadh was
      undertaken. Family and maternal history, physical examination with special
      attention to the cardiovascular system, and echocardiography were performed. A
      total of 100 consecutive IDMs examined. The most common echocardiographic
      findings were patent ductus arteriosus (PDA; 70%), patent foramen ovale (68%),
      atrial septal defect (5%), small muscular ventricular septal defect (4%), mitral
      valve prolapse (2%), and pulmonary stenosis (1%). Hypertrophic cardiomyopathy
      (HCMP) was observed in 38% of cases, mainly hypertrophy of the interventricular
      septum. Severe forms of CHD encountered were D-transposition of great arteries,
      tetralogy of Fallot, and hypoplastic left heart syndrome (1% each). Isolated
      aortic stenosis and coarctation of aorta were not encountered in this series.
      Overall incidence of congenital heart disease was 15% after excluding PDA and
      HCMP. Maternal IDDM is a significant risk factor for CHD. Careful evaluation and
      early diagnosis of CHD in this high-risk group are highly indicated. There is a
      need for development of prenatal screening programs for CHD in our population.

PMID- 14648002
TI  - Long-term efficacy of atenolol for atrioventricular reciprocating tachycardia in
      children less than 5 years old.
AB  - Atrioventricular reciprocating tachycardia (AVRT) using an accessory pathway is
      the most common supraventricular tachycardia observed in infancy and childhood.
      There is a general agreement to treat children older than 5 years who are on a
      potentially long-term antiarrhythmic agent with radiofrequency catheter ablation.
      Atenolol, a relatively long-acting and cardioselective beta-adrenoceptor blocker,
      has been used to control the various types of supraventricular tachycardia in
      children and adults. There are few reports on the use of atenolol in children <5
      years old with AVRT. This retrospective study reports our experience in 22
      children <5 years old (median age, 20 months) who received atenolol monotherapy
      between 1995 and 2001 for treatment of AVRT. AVRT was confirmed in 17 patients by
      transvenous or transesophageal electrophysiologic study and in 5 patients by
      documented preexcitation on electrocardiograms. In nine patients atenolol was the
      first antiarrhythmic drug given. In 15 of the 22 patients (68%) therapy with
      atenolol was considered successful. The average effective dose of atenolol in
      these 15 patients was 1.2 +/- 0.3 mg/kg/day. During a median follow-up of 41
      months (8-74 months), atenolol had been discontinued in 10 patients and no
      further attacks of tachycardia occurred except in 1 patient. In no case did the
      drug have to be withdrawn for adverse effects. In conclusion, this retrospective
      study shows that atenolol as a monotherapy is efficient and relatively safe in
      the long-term treatment of AVRT in young children. Atenolol can be recommended as
      a first-line treatment option for the management of AVRT in infants and young
      children.

PMID- 14648004
TI  - Right atrial isomerism in four siblings.
AB  - Heterotaxy syndromes, right or left atrial isomerism, result from disruption of
      left-right axis determination and their manifestations include complicated heart
      defects. Recent studies in model organisms have revealed complex genetic pathways
      and several genes involved in this process. In affected humans, however,
      molecular studies have identified mutations in a small number of individuals,
      while in most the cause remains unknown. Furthermore, although family data
      suggest, autosomal recessive inheritance, such genes have not yet been
      identified. We have studied six members of a family, four children affected with
      right atrial isomerism (RAI) and their healthy parents, for disturbances of left
      right axis development. The children, one female and three males who all had
      complicated heart defects, succumbed and had an autopsy. Their nonconsanguineous
      parents were examined by cardiac and abdominal ultrasound or MRI. In all four
      children the heart defects included single ventricle with dysplastic
      atrioventricular (AV) valve, total anomalous pulmonary venous drainage (TAPVD),
      and malposition of great arteries (MGA) with pulmonary stenosis (PS). All had
      asplenia; two also had dextrocardia and abdominal situs inversus. The diagnosis
      of RAI was made postnatally in the first child and prenatally in others. Two
      siblings had no surgery and died as a newborn, one with obstructed supracardiac
      TAPVD and the other with regurgitating AV valve. Two children underwent heart
      surgery. One had repair of obstructive infracardiac TAPVD but died in infancy.
      The other underwent both hemi-Fontan operation and heart transplantation but died
      at the age of 2 years. This is the first report describing four children with RAI
      in the same family. The occurrence of RAI in male and female siblings without any
      indication of left-right axis abnormalities in their parents suggests autosomal
      recessive inheritance of human isomerism.

PMID- 14648006
TI  - Value of MRI of the brain in patients with systemic lupus erythematosus and
      neurologic disturbance.
AB  - Our objective was to review the frequency and pattern of signal abnormalities
      seen on conventional MRI in patients with suspected neuropsychiatric systemic
      lupus erythematosus (NP-SLE). We reviewed 116 MRI examinations of the brain
      performed on 85 patients with SLE, (81 women, four men, aged 21-78 years, mean
      40.6 years) presenting with neurological disturbances. MRI was normal or nearly
      normal in 34%. In 60% high-signal lesions were observed on T2-weighted images,
      frequently in the frontal and parietal subcortical white matter. Infarct-like
      lesions involving gray and white matter were demonstrated in 21 of cases. Areas
      of restricted diffusion were seen in 12 of the 67 patients who underwent
      diffusion-weighted imaging. Other abnormalities included loss of brain volume,
      hemorrhage, meningeal enhancement, and bilateral high signal in occipital white
      matter. The MRI findings alone did not allow us to distinguish between
      thromboembolic and inflammatory events in many patients. Some patients with
      normal MRI improved clinically while on immunosuppressive therapy. More sensitive
      and/or specific imaging methods, such as spectroscopy and perfusion-weighted
      imaging, should be investigated in these subgroups of patients with suspected NP
      SLE.

PMID- 14648007
TI  - MRI and intraoperative findings in cavernous haemangiomas of the spinal cord.
AB  - More sensitive imaging techniques, such as MRI, have led to an increase in the
      number of reported cases of spinal cord cavernous haemangioma (SCCH). Complete
      surgical resection has been performed with good outcomes. However, operative
      findings do not always confirm preoperative MRI as to the size and site
      (superficial or deep) of the lesion. We evaluated whether MRI can be used to
      predict whether or not SCCH reach the surface of the spinal cord, since this has
      an impact on surgical strategy. We reviewed the preoperative MRI, case-notes and
      video recordings of 12 patients who underwent surgery, at which five superficial
      and seven deep-seated lesions were identified. T1-weighted images correctly
      indicated the site of the lesion in ten, T2-weighted images in only eight. One
      deep lesion was thought to be superficial on both T1- and T2-weighted images.
      Intravenous contrast medium was not helpful in diagnosis or localisation. In no
      case was a surgically proven superficial lesion interpreted as deep in the spinal
      cord.

PMID- 14648008
TI  - The effects of frequency-encoding gradient upon detectability of the margins and
      height measurements of normal adult pituitary glands.
AB  - We investigated the effects of frequency-encoding gradient (FEG) upon
      detectability and height measurements of the normal adult pituitary gland. We
      obtained two sets of T1-weighted sagittal images of the pituitary gland from 70
      adult subjects without known pituitary dysfunction using 1.5 tesla imagers; one
      with an inferior-superior FEG, and one with an anterior-posterior FEG. We
      classified the subjects into three types according to the distribution of fatty
      marrow in the clivus. Each set of images was assessed for pituitary height on
      midline sagittal images, and detectability of pituitary margins. Height
      measurements and detectability scores were evaluated for significant difference
      between the two FEGs. In subjects with fatty marrow in the clivus, there was
      significant difference between pituitary height measurements (P < 0.005) and
      pituitary margin detectability (P < 0.001). Care should be taken to image the
      pituitary gland using an anterior-posterior FEG.

PMID- 14648009
TI  - Risedronate rapidly reduces the risk for nonvertebral fractures in women with
      postmenopausal osteoporosis.
AB  - Prevention of nonvertebral fractures, which account for a substantial proportion
      of osteoporotic fractures, is an important goal of osteoporosis treatment.
      Risedronate, a pyridinyl bisphosphonate, significantly reduces clinical vertebral
      fracture incidence within 6 months. To determine the effect of risedronate on
      osteoporosis-related nonvertebral fractures, data from four large, randomized,
      double-blind, placebo-controlled, Phase III studies were pooled and analyzed. The
      population analyzed consisted of postmenopausal women, with and without vertebral
      fractures, who had low bone mineral density (lumbar spine T-score <-2.5).
      Patients received placebo (N = 608) or risedronate 5 mg daily (N = 564) for 1 to
      3 years. At baseline, 58% had at least one prevalent vertebral fracture, and the
      mean lumbar spine T-score was -3.4. Among placebo-treated patients, the presence
      of prevalent vertebral fractures did not increase the risk of incident
      nonvertebral fractures overall, although fractures of the humerus and hip and
      pelvis were more common in patients who had prevalent vertebral fractures than in
      those who did not. Risedronate 5 mg significantly reduced the incidence of
      nonvertebral fractures within 6 months compared with control. After 1 year,
      nonvertebral fracture incidence was reduced by 74% compared with control ( P =
      0.001), and after 3 years, the incidence was reduced by 59% ( P = 0.002). The
      results indicate that risedronate significantly reduces the incidence of
      osteoporosis-related nonvertebral fractures within 6 months.

PMID- 14648010
TI  - Bone turnover markers and PTH levels in surgical versus natural menopause.
AB  - In order to assess similarities and differences in women that suffer surgical
      versus natural menopause, a series of bone, clinical, and biochemical parameters
      was assayed in a clinical sample of 35 women with surgical menopause and 112
      women with natural menopause. Biochemical parameters included hormones
      [parathyroid hormone (PTH) and the sex steroids estradiol and testosterone] and
      several markers of bone turnover measured in urine (N-telopeptide and
      calcium/creatinine ratio) or serum (osteocalcin, total alkaline phosphatase,
      total and ionic calcium, phosphate, and magnesium). In addition to type of
      menopause, women were divided by years since menopause (ysm </= 2 or >2). To
      detect differences and relationships between variables, ANOVA, ANCOVA, and linear
      regression analyses were used. Only N-telopeptide, one resorption marker, was
      significantly affected by the variable years since menopause </=2 or >2 ( P
      <0.01), but not by type of menopause. The age-corrected level of PTH was
      significantly decreased in the surgical menopause group ( P < 0.05). In
      conclusion, type of menopause did not impose significant differences in bone
      turnover markers. PTH, one powerful resorption hormone, was diminished in
      surgical menopause.

PMID- 14648011
TI  - Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in
      elderly women in summer and winter.
AB  - Vitamin D2 and D3 are generally considered equipotent in humans. A few studies
      have reported that serum 25OHD levels are higher in vitamin D3- compared with
      vitamin D2-supplemented subjects. As both vitamin D2 and D3 supplements are
      commonly used by elderly in United States, in the present study we determined the
      effect of self-reported vitamin D2 and vitamin D3 supplement use on serum total
      25OHD levels according to season in elderly women aged 65-77 years. Serum total
      25OHD levels were determined in winter and summer in unsupplemented women ( N =
      307) and in women who reported taking vitamin D2 ( N = 56) and vitamin D3 ( N =
      55) supplements by competitive protein binding assay. In vitamin D2-supplemented
      women, the contribution of vitamin D2 and D3 to the mean serum total 25OHD level
      was assessed by HPLC. In summer, there were no significant differences in the
      mean total serum 25OHD levels (ng/ml) among the vitamin D2 (32 +/- 2.1), vitamin
      D3 (36.7 +/- 1.95), and unsupplemented (32.2 +/- 0.95) groups. In winter, the
      mean serum total 25OHD levels were higher in women on vitamin D2 (33.6 +/- 2.34,
      P < 0.05) and vitamin D3 (29.7 +/- 1.76, NS) supplements compared with
      unsupplemented women (27.3 +/- 0.72). In vitamin D2-supplemented women, about 25%
      of the mean serum total 25OHD was 25OHD2, in both summer and winter. Twelve
      percent of unsupplemented women and 3.6% of vitamin D-supplemented women had a
      mean serum total 25OHD level below 15 ng/ml in winter. In elderly subjects, both
      vitamin D2 and Vitamin D3 supplements may contribute equally to circulating 25OHD
      levels, with the role of vitamin D supplement use being more predominant during
      winter.

PMID- 14648013
TI  - A multimodal brain-based feedback and communication system.
AB  - The Thought Translation Device (TTD) is a brain-computer interface based on the
      self-regulation of slow cortical potentials (SCPs) and enables completely
      paralyzed patients to communicate using their brain potentials. Here, an extended
      version of the TTD is presented that has an auditory and a combined visual and
      auditory feedback modality added to the standard visual feedback. This feature is
      necessary for locked-in patients who are no longer able to focus their gaze. In
      order to test performance of physiological regulation with auditory feedback 54
      healthy participants were randomly assigned to visual, auditory or combined
      visual-auditory feedback of slow cortical potentials. The training consisted of
      three sessions with 500 trials per session with random assignment of required
      cortical positivity or negativity in half of the trials. The data show that
      physiological regulation of SCPs can be learned with auditory and combined
      auditory and visual feedback although the performance of auditory feedback alone
      was significantly worse than with visual feedback alone.

PMID- 14648014
TI  - Slowing fastest finger movements of the dominant hand with low-frequency rTMS of
      the hand area of the primary motor cortex.
AB  - Neuroimaging studies suggest that the primary hand motor area and the cerebellum
      play a pivotal role in the control of finger tapping, but their differential
      contribution in this task is unknown. We used therefore repetitive transcranial
      magnetic stimulation (rTMS) in its virtual lesion mode (1 Hz, 10 min, 90% of
      motor threshold) to study the effects of transient disruption of the right
      lateral cerebellum (CB), the left primary hand motor area (M1), and the right
      brachial plexus (PL, control site) on various finger tapping tasks (paced finger
      tapping task: PFT; tapping with maximum speed: TAPMAX, and tapping with
      convenient speed: TAPCON) in healthy right-handed subjects. RTMS of the left M1
      slowed finger tapping speed of the right hand in the TAPMAX task. This effect
      eliminated the right hand superiority in the TAPMAX task. In addition, rTMS of
      the left M1 resulted in slower tapping speeds for both hands during TAPCON. There
      were no other effects of rTMS on tapping speed or tapping variability. Findings
      indicate that M1 is essential for generating fastest finger movements.

PMID- 14648015
TI  - Influence of working memory on patterns of motor related cortico-cortical
      coupling.
AB  - Working memory is implicated in various higher-order cognitive operations. We
      hypothesized that the availability of a temporal representation in working memory
      would limit the extent of cortico-cortical coupling necessary to undertake a self
      paced rhythmic movement. To this end we examined modulations in cortico-cortical
      interactions as determined by EEG coherence during a delay interval and
      subsequent movement reproduction. Right hand movement was initially paced by a
      metronome beat every 0.9 s, followed by a delay interval, after which hand
      movement was repeated in an unpaced manner. Movement reproduction after a long
      (22.5 s, corresponding to 25 movement cycles) compared to a short (5.4 s,
      corresponding to 6 movement cycles) delay interval was associated with an
      increased degree of functional coupling in the beta frequency band (12-30 Hz) of
      the left (movement-driving) hemisphere (F3-FC3, F3-C3 and F3-P3 connections) as
      well as mesial regions (FCz-FC3, FCz-C3 and Cz-FC3 connections) even though
      overall behavioral characteristics were not influenced. In addition, analysis of
      the EEG coherence in the delay period revealed a bilateral frontal network (F3
      F4, F3-FC4, F4-FC3 and FC3-FC4 connections). Activity in the latter tended to be
      synchronized in the theta band (4-8 Hz) and was significantly less strong at 22.5
      s than 5.4 s. These data suggest that working memory may be partly subserved by
      synchronization in a bilateral frontal network and may provide an intrinsic
      contextual influence that shapes the pattern of cortico-cortical interaction
      during a given task.

PMID- 14648016
TI  - Interferon-gamma pharmacokinetics and pharmacodynamics in patients with
      colorectal cancer.
AB  - PURPOSE: The study objectives were to define subcutaneous (s.c.) interferon gamma
      (IFN-gamma) disposition in patients with gastrointestinal malignancies receiving
      5-fluorouracil (5-FU) and leucovorin (LV) and to examine the relationship between
      IFN-gamma exposures and Fas upregulation in vivo and in vitro. METHODS: Patients
      received IFN-gamma (10, 25, 50, 75, and 100 microg/m(2)) with LV and 5-FU, and
      serial samples were collected after the first dose. IFN-gamma concentrations were
      measured by ELISA. A linear one-compartment model with a lag was fitted to the
      IFN-gamma plasma concentration-time data. To examine the relationship between IFN
      gamma systemic exposure and biological activity in vivo, cell surface Fas
      upregulation was assessed in peripheral blood mononuclear cell (PBMC)
      subcompartments. RESULTS: The median (range) apparent IFN-gamma clearance was 46
      l/m(2) per hour (2.6-92 l/m(2) per hour). With increasing IFN-gamma dosages, the
      area under the concentration-time curve (AUC(0--> infinity )) and C(max)
      increased; however, significant interpatient variability was observed. IFN-gamma
      AUC(0--> infinity ) and time above 33.3 pg/ml significantly correlated with Fas
      upregulation in several PBMC compartments, but dosage was significantly
      correlated with this pharmacodynamic marker only in CD4(+) and CD56(+) cells. In
      vitro studies in HT29 cells demonstrated that clinically relevant IFN-gamma
      concentrations (1 to 10 U/ml for 6.5 h) with 5-FU/LV upregulated Fas expression
      3.5-fold, similar to that in PBMC in vivo. CONCLUSIONS: We characterized IFN
      gamma disposition and developed a limited sampling model for use in future
      pharmacokinetic studies. Our results showed that IFN-gamma upregulates Fas in
      PBMC in vivo and in HT29 cells in vitro at tolerable, clinically relevant
      exposures and that monitoring IFN-gamma pharmacokinetics/pharmacodynamics may be
      warranted in IFN-gamma clinical use.

PMID- 14648017
TI  - Cross-resistance to cisplatin in cells with acquired resistance to copper.
AB  - PURPOSE: Cells selected for resistance to cisplatin (DDP) demonstrate cross
      resistance to copper (Cu) suggesting one or more common mechanisms of cellular
      defense. We sought to determine whether cells selected for resistance to Cu are
      cross-resistant to DDP. MATERIALS AND METHODS: Parental HuH7 human hepatoma cells
      and the CuR27 Cu-resistant subline were compared for sensitivity to Cu and DDP by
      clonogenic assay, and with respect to drug uptake and efflux by measuring
      cellular Cu and Pt content. RESULTS: CuR27 cells were found to be 1.8-fold
      resistant to Cu and 8.6-fold cross-resistant to DDP. Changes in the cellular
      pharmacokinetics of Cu in the CuR27 cells were paralleled by changes in the
      kinetics of DDP. The accumulations of Cu and DDP measured at 1 min were,
      respectively, 36% and 26% of those in the parental HuH7 cells. The initial rate
      of efflux from the CuR27 cells was 6.2-fold faster for Cu and 2.5-fold faster for
      DDP than from the HuH7 cells. Cu reduced the accumulation of DDP in the HuH7
      cells in a concentration-dependent manner and vice versa. DDP also reduced the
      efflux of Cu. Western blot analysis demonstrated that expression of the Cu
      exporter ATP7B was increased 3.9-fold in the CuR27 cells. CONCLUSIONS: In this
      model system, cross-resistance between Cu and DDP was bidirectional and
      accompanied by parallel changes in the cellular pharmacokinetics of both
      compounds. The results are consistent with the idea that transporters and
      chaperones that normally mediate Cu homeostasis also directly or indirectly
      modulate the accumulation of DDP.

PMID- 14648018
TI  - Serine/threonine protein phosphatase inhibition enhances the effect of
      thymidylate synthase inhibition.
AB  - PURPOSE: The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key
      enzymes in regulating entry into the cell cycle, mitosis and apoptosis.
      Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating
      in G(2)/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key
      regulatory enzyme in DNA synthesis, inhibition of which is often a first-line
      treatment for colorectal carcinoma. In this study the effect of combining PP
      inhibition with TS inhibition in two colorectal cell lines was examined. METHODS:
      Cantharidin and nolatrexed were used to inhibit PP and TS activity, respectively.
      The MTT cytotoxicity assay and cell cycle analysis were performed following
      single-drug treatment of HT29 and HCT116 colorectal cell lines. The median effect
      method was used to determine a combination index (CI), where drug antagonism was
      indicated by a CI>1.1, additivity by a CI between 0.9 and 1.1, and synergism by a
      CI<0.9. RESULTS: Both cell lines were equally sensitive to cantharidin alone
      (GI(50) values 5.4 and 7.3 micro M), which induced a significant increase in the
      S-phase population of both cell lines within 6 h with a concomitant increase in
      DNA synthesis. This response culminated in G(2)/M cell cycle arrest within 24 h
      and subsequent cell death. In response to nolatrexed alone, HT29 cells were more
      sensitive than HCT116 cells (GI(50) 1.9 micro M vs 9.8 micro M), with G(1)/S
      phase cell cycle arrest occurring within 24 h in both cell lines. In HT29 cells,
      this was followed by cell death, whereas in HCT116 cells, a proportion of cells
      died following arrest but the predominant event was re-entry into the cell cycle.
      The simultaneous exposure of HT29 cells to the combination of nolatrexed and
      cantharidin in drug molar ratios of 1:1 and 1:2.5 for 72 h was synergistic
      producing composite CIs of 0.88 and 0.87, respectively. The sequence of
      nolatrexed followed by cantharidin 24 h later resulted in greater synergism (CI
      values of 0.75, 0.52, 0.55, 0.68 for molar ratios of 10:1, 1:1, 1:2.5, 1:10),
      whereas the reverse sequence was antagonistic, suggesting that the point of
      interaction is downstream of TS inhibition. In HCT116 cells only additive and
      antagonistic interactions were observed for any of the treatment combinations.
      The lack of synergism in these cells may be caused by the reduced sensitivity of
      these cells to nolatrexed as a single agent. CONCLUSION: The effect of TS
      inhibition can be enhanced by the inhibition of serine/threonine protein
      phosphatases.

PMID- 14648019
TI  - Imatinib and beyond--the new CML study IV. A randomized controlled comparison of
      imatinib vs imatinib/interferon-alpha vs imatinib/low-dose AraC vs imatinib after
      interferon-alpha failure in newly diagnosed chronic phase chronic myeloid
      leukemia.

PMID- 14648020
TI  - Combination therapy of disseminated Fusarium oxysporum infection with terbinafine
      and amphotericin B.
AB  - A case of disseminated infection with Fusarium oxysporum following chemotherapy
      of acute myelogenous leukemia is reported. Antifungal treatment was successful
      with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with
      amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous
      liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B
      deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The
      combination therapy described here represents a novel approach to the treatment
      of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to
      cause disseminated infection with high mortality.

PMID- 14648023
TI  - Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current
      knowledge and future prospects.
AB  - After rapid improvement of treatment results in adult acute lymphoblastic
      leukemia (ALL) from less than 10% to 30-40% in the past decades, more recently
      stagnation has been observed. In addition, a borderline for further
      intensification of chemotherapy appears to be reached in adult ALL patients. New,
      preferably non-chemotherapy, approaches are therefore urgently required. One of
      those is targeted therapy with monoclonal antibodies (MoAbs). ALL blast cells
      express a variety of specific antigens which may serve as targets, such as CD19,
      CD20, CD22, CD33, and CD52. Published results of MoAbs in ALL are reviewed. Most
      experience is available for anti-CD20 (rituximab) which led to a significant
      improvement of the outcome in B-cell non-Hodgkin's lymphoma (NHL). In ALL,
      rituximab is combined with chemotherapy mainly in mature B-ALL and Burkitt's
      lymphoma and preliminary results are promising. In the future, studies will also
      be done in B-precursor ALL. Another promising B-cell antibody is anti-CD22.
      Several CD19 MoAbs were also tested in phase I studies. However, results are not
      conclusive and these MoAbs are not generally available. Far less experience with
      MoAb therapy is available for T-ALL, but clinical studies are on the way with
      anti-CD52 and anti-CD25 in adult T-cell leukemia/lymphoma. Overall, it can be
      stated that MoAb therapy in ALL is a promising treatment approach. Monotherapy
      with MoAbs in relapsed ALL occasionally led to responses, but higher effectivity
      can be expected from a combination with chemotherapy and treatment in the state
      of minimal residual disease. Well-designed studies and joint efforts are required
      to explore optimal combinations, timing and dosage of MoAb therapy in ALL.

PMID- 14648024
TI  - All- trans-retinoic acid-induced erythema nodosum in patients with acute
      promyelocytic leukemia.
AB  - Erythema nodosum associated with all- trans-retinoic acid (ATRA) for acute
      promyelocytic leukemia (APL) is very rare. We describe four patients with classic
      APL who developed erythema nodosum during ATRA therapy. Fever and subsequent
      multiple painful erythematous nodules over extremities developed on D11, D16,
      D17, and D19, respectively, after ATRA therapy. The skin biopsy taken from each
      patient was consistent with erythema nodosum. All patients received short course
      of steroids. Fever subsided rapidly and the skin lesions regressed completely.
      All patients achieved complete remission without withdrawal of ATRA. ATRA seemed
      to be the most possible etiology of erythema nodosum in our patients. Short-term
      use of steroid is very effective in ATRA-induced erythema nodosum.

PMID- 14648025
TI  - Presentation assessment of minor histocompatibility antigens by predictive
      proteasomal cleavage analysis.
AB  - Minor histocompatibility peptides (mHps) derived from polymorphic segments of
      endogenous proteins are thought to be targets for graft-versus-host and graft
      versus-leukemia reactions after HLA-identical stem cell transplantation. A great
      majority of antigenic peptides is generated by fragmentation of proteins in the
      course of proteasomal processing. An algorithm was recently developed to predict
      cleavage sites during proteasomal processing. We tested the accuracy of the
      algorithm to predict mHps using 18 amino acid (AA) sequences of minor
      histocompatibility antigens (mHags) encoded by autosomal genes representing
      single nucleotide polymorphisms or by Y-chromosomal genes. The algorithm
      correctly predicted the C-termini of 11 of 13 experimentally confirmed mHps: 1)
      Correct prediction of C- and N-termini, e.g., for HA-1(H); 2) Correct prediction
      of C- and N-termini while anticipating intra-epitope cleavage sites, e.g., for
      SMCY-A*0201; 3) Correct prediction of C-termini and N-terminal extensions, e.g.,
      for HA-8(R/V); and 4) Correct prediction of C-termini and N-terminal extensions
      while anticipating intra-epitope cleavage sites, e.g., for UTY-B8. Analysis of
      experimentally unconfirmed allelic counterparts of four autosomal mHags showed
      that AA substitutions either led to the insertion of an epitope-destroying
      cleavage site (e.g., in HA-1(R)) or abolished the correct C-terminus (e.g., in HA
      2(M)). The proteasomal processing algorithm provides reliable data on the
      generation of mHps and forecasts their presence or absence. Combined with MHC
      class I ligand prediction, it can be a useful tool for the prediction of
      generation and presentation of new CTL epitopes derived from minor
      histocompatibility antigens.

PMID- 14648027
TI  - Allogeneic hematopoietic stem cell transplantation in a patient affected by large
      granular lymphocyte leukemia and multiple sclerosis.
AB  - We describe a 57-year-old man, affected by large granular lymphocyte (LGL)
      leukemia and concomitant primary progressive multiple sclerosis (MS), treated
      with allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA
      identical sibling. The patient was conditioned with fludarabine, busulphan, and
      cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis consisted of
      cyclosporine and short-term methotrexate. At 3 years follow-up, the patient is in
      complete remission of LGL with a marked improvement in neurological conditions.
      This is the first case of allogeneic HSCT in a patient with LGL leukemia and
      concomitant primary progressive MS. Allogeneic HSCT, performed in our patient to
      cure the lymphoproliferative disorder, improved the clinical course of MS.

PMID- 14648028
TI  - Unusual and severe symptomatic impairment of neutrophil function after one cycle
      of temozolomide in patients with malignant glioma.
AB  - Temozolomide, a recently approved cytotoxic agent for the treatment of malignant
      glioma, has shown promising results in the treatment studies published so far.
      However, cytopenia and related infectious complications have been reported in 2
      8% of cases. Here we present three treatment-naive patients with malignant glioma
      experiencing cytopenia and/or infectious complications after the first cycle of
      temozolomide. Neutrophils obtained from each patient up to 6 weeks after the end
      of the temozolomide application showed normal phagocytic capacity but decreased
      oxygen radical production and thus impairment of microcidal activity. Our data
      suggest that a prolonged impairment of the immunological defense may occur in
      temozolomide-treated patients.

PMID- 14648030
TI  - Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG)
      experience.
AB  - This is a retrospective, multicenter study to evaluate biological features and
      outcome of elderly patients diagnosed with acute lymphoblastic leukemia (ALL)
      during the last 10 years in ten hematological centers in Poland. Eighty-seven
      patients aged 60 years or older were studied. To our knowledge, this is one of
      the largest group of elderly patients with ALL evaluated. We have not observed
      differences in immunological subtypes and Ph chromosome incidence as compared
      with younger adult ALL presented in the literature. Induction chemotherapy was
      administered in 75 patients. We observed complete remission (CR) in 34 (45%, 95%
      CI: 33-56%) patients. Induction death occurred in 11 (15%) patients. Thirty
      patients (40%) showed primary resistance to chemotherapy. Median overall survival
      (OS) of all patients was 150 days. Median disease-free survival (DFS) of
      responding patients was 180 days. We observed four long-term survivors (DFS
      longer than 3 years) in our group of patients. Factors influencing OS were CR
      achievement, female gender, and WBC below 30 x 10(9)/l. Male gender was the only
      prognostic factor negatively affecting probability to achieve CR. We have not
      observed any differences in either biology or outcome between patients aged 60-69
      years and those aged more than 70 years. ALL of the elderly is a rare disease
      with poor prognosis. Further clinical trials evaluating the disease features,
      outcome, and new therapeutic approaches are warranted.

PMID- 14648032
TI  - A randomized multicenter open label phase II study to determine the safety and
      efficacy of induction therapy with imatinib (Glivec, formerly STI571) in
      comparison with standard induction chemotherapy in elderly (>55 years) patients
      with Philadelphia chromosome-positive (Ph+/BCR-ABL+) acute lymphoblastic leukemia
      (ALL) (CSTI571ADE 10).

PMID- 14648033
TI  - Intrinsic proportions of the human tarsus: an original approach to tarsal
      biometry.
AB  - Few precise biometrical data on human tarsal bones are available, and those
      published consist principally of linear and angular measurements made on dried
      bones or on radiographs. The material consisted of 86 complete adult human tarsi
      (dried bones). The tarsal proportions were determined using the relative tarsal
      weights (Weight of each of the seven tarsal bones/Weight of the total
      tarsusx100). The calcaneus was the greatest tarsal bone (41.95%), and the talus
      the second-largest (28.45%). The medial cuneiform, the cuboid, and the navicular
      had very similar proportions (7.00-8.38%), as did the intermediate and lateral
      cuneiforms (2.98% and 3.81%). The study of the ranks of each bone by decreasing
      proportion allowed the determination of individual variability. The posterior
      tarsal row was considerably larger (70.40%) than the anterior row (29.60%),
      resulting in an antero-posterior ratio of 0.42. The medial and lateral tarsal
      columns had quite similar proportions (50.63% and 49.37%), resulting in a latero
      medial ratio of 0.98. The intrinsic tarsal proportions are fundamental
      biometrical data which seem to be of interest for a better characterization of
      the human foot in clinical practice and for quantitative approaches in functional
      and comparative morphology and in paleontology.

PMID- 14648034
TI  - Morphology and imaging of bony projections on sigmoid sulcus with clinical
      implication.
AB  - Morphologically diverse osseous projections were observed on the anterior lip of
      the sigmoid sulcus in a study conducted on 318 dry unsexed adult human skulls
      belonging to the Indian race. For convenience of description, this lip was
      divided into a longer lateral part, a shorter medial part and a junctional
      angular part having bony attributes characterized into three types, crests
      (42.9%), plates (22.3%) and bridges (13.5%). The bridges were subtyped into
      incomplete (11.8%) and complete (1.7%). Crests and plates were present anywhere
      along this lip, while bridges were confined to the angle. Right and left
      differences were analyzed, which showed that the above findings were more
      frequent on the right than the left. Plates showed a higher incidence of
      variation between right and left sides as compared to crests and bridges. Five
      cadavers were studied, which showed retinacular bands attached to the projections
      blending with dura mater over the foramen magnum. It is postulated that these
      projections are caused by the traction of the fibrous dural bands. Axial CT scan
      revealed partial and complete osseous bridges spanning the sulcus. These
      projections are of relevance to surgeons working at the cerebellopontine angle.
      Their presence has not been reported previously.

PMID- 14648035
TI  - Retrograde portography of the right caudate lobe via the middle hepatic vein.
AB  - Hepatobiliary resection with caudate lobectomy has been conducted in the surgical
      treatment of bile duct carcinoma of the hepatic hilus. However, insufficient
      attention has been paid to the anatomy of the right portion of the caudate lobe,
      and techniques to visualize the portal branches of the right caudate lobe (P1r)
      have not been reported. Contrast medium was injected into the dorso-caudal
      branches of the middle hepatic vein (MHV) and images were obtained by digital
      subtraction venography. Retrograde portography of the P1r was achieved in 64
      (84%) out of 76 cases. The mean number of visualized branches was 2.1 (137 out of
      64) and the P1r coursed beyond the trunk of the MHV in 36 (56%) out of the 64
      cases. Contrast medium flowed into the right portal vein from 59 P1r branches in
      32 cases and into the left portal vein in 20 cases. No complications were
      encountered. Retrograde portograms of the P1r may provide valuable information
      not previously available to surgeons operating on the caudate lobe.

PMID- 14648036
TI  - Study of the carrying angle of the human elbow joint in full extension: a
      morphometric analysis.
AB  - This study measured the carrying angle of the elbow joint in full extension in
      600 students, using the supplementary angle to that between the longitudinal axis
      of the arm and that of the forearm. The mean carrying angle was 12.88 degrees +/
      5.92: 10.97 degrees +/-4.27 in men and 15.07 degrees +/-4.95 in women. The
      carrying angle changes with skeletal growth and maturity. The angle is always
      greater on the side of the dominant hand. We confirmed the inverse relationship
      between the carrying angle and the intertrochanteric diameter. Also, the type of
      constitution influences the value of the carrying angle, especially in women.

PMID- 14648037
TI  - The pterion in Turkish male skulls.
AB  - This study was conducted to determine the location and type of pterion in Turkish
      males. The importance of the pterion is its relation to the middle meningeal
      artery, Broca's motor speech area on the left side, and surgical interventions
      relating to pathologies of the sphenoid ridge and optic canal. Specific
      measurements were taken on both sides of 26 Turkish human male skulls, none of
      which showed any obvious pathology or trauma. The sphenoparietal type of pterion
      was the most common (96% right side, 79% left side), followed by the
      frontotemporal (4% right side, 17% left side), and finally the epipteric type (4%
      left side only). The distances on the right and left sides respectively from the
      center of the pterion to the frontozygomatic suture were 3.30+/-0.40 cm and
      3.44+/-0.39 cm, to the zygomatic arch 4.05+/-0.39 cm and 3.85+/-0.25 cm, to the
      optic canal 4.39+/-0.40 cm and 4.36+/-0.40 cm, and to the sphenoid ridge 1.40+/
      0.33 cm and 1.48+/-0.32 cm. The thickness of the skull at the center of the
      pterion was 0.41+/-0.14 cm and 0.39+/-0.12 cm on the right and left sides
      respectively. These findings should be of use in surgical approaches and
      interventions via the pterion.

PMID- 14648038
TI  - Morphologic study of left ventricular bands.
AB  - The presence of left ventricular bands has drawn attention to their possible
      clinical importance, though there are no concrete data to support their role in
      serious clinical diseases. We have investigated the incidence, location,
      microscopic and macroscopic structure of left ventricular bands in the human and
      animals. We examined 100 hearts: 28 human and 72 animal (dog, goat, sheep). Left
      ventricular bands were present in 13 of 28 (46%) human hearts and 62 of 72 (86%)
      animal hearts. The bands usually extended from the interventricular septum to the
      free walls in human hearts and from the papillary muscles to the interventricular
      septum in animal hearts. They were composed of muscle tissue in various
      proportions in human and dog hearts, and of connective and conductive tissue in
      sheep and goat hearts.

PMID- 14648039
TI  - A safe area and angle for harvesting autogenous tendons for anterior cruciate
      ligament reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction with autogenous semitendinosus
      and gracilis tendons has become a common surgical procedure. Lower leg
      paresthesia following injury to the infrapatellar nerve during harvesting of the
      tendons has been well documented. Few authors have described the position of the
      infrapatellar nerve on a flexed knee, which is the position used during ACL
      reconstruction. The purpose of this study was to determine a safe area and angle
      where an incision could be made for harvesting of the semitendinosus and gracilis
      tendons, with the knee in flexion. Twenty right cadaver knees and 20 left knees
      were dissected. Landmarks on the knee were identified, from where the distances
      to the nerves (infrapatellar and saphenous) were measured with a vernier caliper.
      A safe area on the right knee was determined to be on the tibial tuberosity plane
      between 3.7 and 5.5 cm with a safe angle of incision of 51.6 degrees. A safe area
      on the left knee was determined to be on the tibial tuberosity plane between 3.6
      and 4.9 cm with a safe angle of incision of 52.5 degrees. The results may assist
      orthopedic surgeons performing ACL reconstruction with semitendinosus and
      gracilis tendons to avoid cutaneous nerve damage and, therefore, patient
      discomfort.

PMID- 14648040
TI  - The external laryngeal nerve: surgical and anatomic considerations. Report of 50
      total thyroidectomies.
AB  - This surgical anatomy study aimed to evaluate the possibility of identifying the
      external laryngeal nerve during thyroid surgery and the possible variations of
      nerves at risk. Fifty patients underwent total thyroidectomies during a period of
      12 months. Using a neurostimulator, the distal motor branch of the external
      laryngeal nerve was searched. Electrical stimulation of a nervous branch aimed to
      provoke a global contraction of the cricothyroid in order to identify with
      certitude the external laryngeal nerve. The external laryngeal nerve was
      identified in 20% of cases. Its course was, with almost equal frequency, either
      (1) between the vessels of the superior thyroid pedicle or (2) superficial and
      anterior to the fascia of the cricothyroid muscle. The external laryngeal nerve
      is hard to find during thyroid surgery, even with a neurostimulator. It can be
      vulnerable during thyroid surgery but only in cases of anatomic variations.
      Searching for the nerve systematically during thyroid surgery does not seem to be
      useful. Several precautions when dissecting the superior pole of the thyroid
      gland seem to be necessary and sufficient to respect the external laryngeal
      nerve.

PMID- 14648041
TI  - Massive upper gastrointestinal bleeding after acid-corrosive injury.
AB  - Our purpose was to delineate the characteristics and outcome of massive upper
      gastrointestinal bleeding (UGI) caused by acid-corrosive injury and to determine
      its management protocol. From June 1988 to June 2000, all patients with the
      history of acid-corrosive injury at our institution were reviewed. Patients with
      massive UGI bleeding (hematocrit level <25% or transfusion of three or more units
      of whole blood required to restore normal vital sign) were enrolled into this
      study. Altogether, 12 (3.2%) of 378 patients with acid-corrosive injury developed
      massive bleeding: 8 gastric bleeding, 2 duodenal bleeding, and 2 first gastric
      and then duodenal bleeding. Gastric bleedings started an average of 12.1 days
      after the initial injury (range 9-21 days). Duodenal bleeding usually occurred
      later, at 10.1 days (range 6-18 days) after a gastric or esophagogastric
      operation. Nine of the ten patients with gastric bleeding underwent surgery
      during the subacute stage: three esophagogastrectomy, three gastric mucosectomy
      with gastrostomy and jejunostomy, and three total or subtotal gastrectomy.
      Operative findings were hemorrhagic gastritis with diffuse mucosal bleeding. Two
      of four patients with duodenal bleeding underwent duodenotomy with suture
      ligation of bleeding vessels, and the other two had conservative treatment. Nine
      patients (75%) had postoperative complications. One patient (8%) died from
      complications of surgery performed to stop duodenal bleeding. Massive UGI
      bleeding rarely occurs after acid-corrosive injury; but when it does, it occurs
      during the subacute stage. Aggressive surgical treatment is mandatory for gastric
      bleeding. How duodenal bleeding can be better managed requires further study.

PMID- 14648042
TI  - Effect of interstitial laser hyperthermia in a murine model of colorectal liver
      metastases: scanning electron microscopic study.
AB  - Interstitial laser hyperthermia (ILH) is an in situ ablative technique used to
      treat colorectal liver metastases. The relatively high recurrence of tumor after
      treatment by ILH may be related to incomplete destruction. Little is known about
      the effectiveness of ILH for destroying tumor microvasculature. The aim of this
      study was to define the changes to the microvascular architecture of tumors after
      treatment with ILH, specifically focusing on the completeness of tumor
      vasculature destruction. An intrasplenic induction model of liver metastases in 4
      to 6-week-old male inbred CBA mice was used. Laser hyperthermia was applied to
      liver and tumor tissue using a bare optical quartz fiber from a Medilas Fibertom
      4100 Nd:YAG surgical laser generator. The animals underwent microvascular
      corrosion casting of the livers immediately after application of ILH.
      Microvascular casts were then prepared and studied by scanning electron
      microscopy. ILH produced complete, uniform destruction of the tumor
      microvasculature with compete hemostasis. Blood flow in vessels larger than 100
      microm diameter had a relatively protective effect, although ILH was able to
      overcome this barrier effectively by increasing the energy applied. ILH produces
      complete destruction of tumor microvasculature with hemostasis. The protective
      effect of blood flow in larger vessels can be overcome by the appropriate use of
      higher energy levels.

PMID- 14648043
TI  - Needle tract implantation of hepatocellular carcinoma and pancreatic carcinoma
      after ultrasound-guided percutaneous puncture: clinical and pathologic
      characteristics and the treatment of needle tract implantation.
AB  - Tumor implantation along the needle tract following percutaneous procedures under
      ultrasonographic guidance for hepatocellular carcinoma (HCC) and pancreatic
      carcinoma (PC) has been well documented. The purpose of the present study was to
      investigate the correlation between the procedure, the pathologic differentiation
      of the primary tumor, and the treatment after implantation. Between July 1992 and
      March 2000, HCC patients (n=372) who underwent biopsy, percutaneous ethanol
      injection (PEI) therapy and percutaneous microwave coagulation therapy (PMCT) and
      PC (n=73) patients who underwent biopsy were retrospectively studied. Needle
      tract implantation was found in six of the HCC patients (1.6%) and one of the PC
      patients (1.4%). The interval to diagnosis ranged from 5 to 25 months (mean +/-
      SD 11.2 +/- 7.6 months) in the HCC patients. The needle tract implantation was
      evident for all procedure types in these patients (two after PEI alone, two after
      both biopsy and PEI, and one after PMCT) and for each degree of pathologic
      differentiation of the primary tumors (well differentiated in one, moderately
      differentiated in two, and poorly differentiated in one). Each implanted tumor
      was surgically resected, with no recurrence at the focal lesion. These results
      suggest that needle tract implantation develops regardless of the procedure or
      the pathologic differentiation of the primary tumor, and that surgical resection
      might be effective for controlling these implanted lesions.

PMID- 14648044
TI  - Role of computer analysis in gastric cancer surgery: evaluation of the
      WinEstimate v. 2.5 computer program.
AB  - To identify the group of patients with gastric cancer who can benefit from
      extensive lymphadenectomy and to offer a rational approach to lymph node
      dissection, it is important to know the incidence of metastases at each lymph
      node station. A computer program was developed for assessment of lymph node
      involvement and survival time in each individual case according to preoperative
      variables. In patients who have undergone R0 resection with D2 lymphadenectomy,
      differences between the individual results generated by the computer and the
      actual data were compared. A cutoff point of 10% in the prediction of metastases
      was used as a positive result. The computer program made false predictions in 9%
      of patients for the pN status (3% lower and 6% higher than the actual status).
      Computerized prediction of 5-year survival was close to the rate calculated by
      the Kaplan-Meier method (55.5% vs 56.1%). Preoperative computer analysis of
      patient data and tumor characteristics offers a rational approach to
      individualizing tumor therapy] where the extent of lymph node dissection is
      tailored to the type, site, and stage of the tumor, thereby minimizing the
      disadvantages (morbidity, mortality) associated with the extensive operative
      procedure.

PMID- 14648045
TI  - Effect of spontaneous portosystemic shunts on hemorrhage from esophagogastric
      varices.
AB  - The role of a massive spontaneous portosystemic shunt (MSPSS) in cirrhotic
      patients with portal hypertension remains unclear. The aim of this study was to
      investigate clinical outcomes and portal hemodynamic changes following ligation
      of the MSPSS during devascularization surgery. Portography and gastroendoscopy
      were performed before and after surgery for hemodynamic and follow-up studies.
      Three types of MSPSS were demonstrated portographically: 22 portoumbilical
      shunts, 18 splenorenal shunts, and 2 inferior mesenteric-caval shunts. A total of
      40 MSPSS patients with esophagogastric variceal (EGV) bleeding underwent surgery:
      26 had ligation of the MSPSS, and the remaining 14 served as the nonligation
      group. Neither the preoperative mean portal pressure (MPP) nor the postoperative
      MPP were significantly different between the ligation and nonligation groups
      (p>0.1), and there was no significant difference regarding surgical mortality,
      recurrent varices, or cumulative survival rate for the two groups in the follow
      up study. However, postoperative portography demonstrated persistent drainage of
      portal flow and decreased intrahepatic portal perfusion in the nonligation
      patients. Clinical signs of hepatic encephalopathy subsided after ligation of the
      MSPSS in three patients. Therefore ligation of the MSPSS, which may be
      responsible for the development of encephalopathy, is recommended during
      devascularization surgery for EGV in cirrhotic patients.

PMID- 14648046
TI  - Usefulness of known computed tomography and clinical criteria for diagnosing
      strangulation in small-bowel obstruction: analysis of true and false
      interpretation groups in computed tomography.
AB  - Computed tomography (CT) criteria have proven useful, but not sufficient, for
      diagnosis of bowel strangulation. The purpose of the present study was to
      evaluate the use of clinical criteria in the interpretation of CT scans as a
      means of improving the diagnostic accuracy of CT, especially in patients whose CT
      scans are equivocal for distinguishing simple obstruction from strangulated
      obstruction. We analyzed the CT scans of 136 patients with simple (n=70) or
      strangulated (n=66) small-bowel obstruction. Three radiologists interpreted the
      CT scans independently for the presence of intestinal strangulation. According to
      their interpretation, 136 patients were divided into two groups, i.e., a false
      and a true interpretation group. The diagnostic value of known CT and four
      clinical criteria (tenderness, tachycardia, fever, and leukocytosis) were
      compared in the two groups. The diagnostic accuracy of CT criteria for
      distinguishing simple obstructions from strangulated small-bowel obstructions
      ranged between 73% and 80%. Of the 136 patients, 31 belonged to the false group
      and 105 to the true group. The CT criteria that were highly specific in both
      groups included severe mesenteric haziness, serrated beak, and poor bowel wall
      enhancement. Among the clinical criteria, both tachycardia and leukocytosis were
      highly specific in both groups. The number of positive clinical criteria was
      helpful in making a diagnosis; none or one clinical criterion indicated a simple
      obstruction, whereas three or four criteria indicated a strangulated obstruction;
      when this result was applied retrospectively to the false group, the CT
      diagnostic accuracy improved in 19 of the 31 patients. The use of clinical
      criteria when CT findings are equivocal, may overcome the inherent limitations of
      CT for diagnosing strangulated small-bowel obstruction.

PMID- 14648047
TI  - Enduring effects of thoracoscopic Heller myotomy for treating achalasia.
AB  - Minimal invasive surgery using a laparoscopic or thoracoscopic approach for
      cardiomyotomy (Heller myotomy) has become a widely accepted procedure to treat
      achalasia of the esophagus. In this study, we evaluated the long-term results of
      Heller myotomy achieved by performing video-assisted thoracic surgery (VATS). We
      recruited patients with achalasia who had undergone VATS for Heller myotomy from
      1991 to 2000 at the National Taiwan University Hospital. The myotomy was
      performed 6 cm above and 1 cm below the gastroesophageal junction. No
      fundoplication was performed during the procedure. The symptom score, which
      included dysphagia, regurgitation, and chest pain, was evaluated before and after
      surgery. Body weight was also recorded before and after surgery. The cases of 14
      patients (4 men, 10 women) were studied. The mean patient age was 41.8 +/- 4.9
      years. No postoperative mortality or morbidity was found in these patients. The
      follow-up duration was 56 +/- 7.17 months. The dysphasia score improved from 3.0
      preoperatively to 0.79 +/- 0.30 postoperatively (p=0.001). The reflux score
      improved from 2.64 +/- 0.17 preoperatively to 0.50 +/- 0.20 postoperatively
      (p=0.001). All the improvements were still in place at the time of the most
      recent follow-up examinations. Heller myotomy to treat achalasia using a
      thoracoscopic approach can provide satisfactory long-term results.

PMID- 14648048
TI  - Management of retrohepatic inferior vena cava injury during hepatectomy for
      neoplasms.
AB  - The aim of this article is to discuss the management of retrohepatic inferior
      vena cava injury during hepatectomy for neoplasms. Step-by-step hepatic vascular
      exclusion, digital compression, finger pinching, and surface-to-surface suturing
      were used in the management of retrohepatic inferior vena cava injury during
      hepatic resection in 16 cases: 12 patients underwent exclusion of the hepatic
      artery and portal vein by portal triad clamping (PTC) only; 3 underwent PTC and
      exclusion of the infrahepatic inferior vena cava (IVC); and 1 underwent PTC
      together with exclusion of the suprahepatic and infrahepatic IVC. In all cases,
      bleeding stopped immediately after the management described, with no
      intraoperative deaths and no postoperative bleeding. The median follow-up was
      42.5 months (range 19-60 months) for all patients, and the 5-year survival rate
      of all patients with malignant tumors was 28.57%. One died of lung metastasis 19
      months after operation, one with spontaneous rupture of a hepatocellular
      carcinoma 19 months after operation, and eight others from recurrence or
      metastasis 21, 23, 24, 27, 30, 35, 50, or 54 months after operation,
      respectively. Two patients had a recurrence 4 years and 4 years 6 months after
      the initial operation, respectively. The recurrent tumors of the liver were
      resected. The other patients are currently alive without recurrence or
      metastasis. The techniques described are safe, simple, practical, time-saving,
      and effective for controlling massive bleeding arising from injury to the
      retrohepatic inferior vena cava during hepatic resection.

PMID- 14648049
TI  - Relation between hepatic and portal veins in the right paramedian sector:
      proposal for anatomical reclassification of the liver.
AB  - Although a right liver graft without a middle hepatic vein resulted in potential
      venous congestion in the right paramedian sector, the details of the hepatic
      venous distribution in the right paramedian sector have not been established. In
      this study, the ramification patterns of the hepatic veins draining the right
      anterosuperior segment (S8) and the relation between the hepatic and portal veins
      were assessed using multislice computed tomography in 44 patients without lesions
      in the liver. All 52 drainage veins of the ventral area of S8 joined the middle
      hepatic vein, and all 48 drainage veins of the dorsal area joined the right
      hepatic vein. The hepatic vein crossing between the ventral and dorsal areas was
      observed in each patient examined. Therefore, we propose a reclassification
      wherein the right paramedian sector is divided into ventral and dorsal segments.
      This new classification may contribute to the development of new and safer
      surgical procedures, including more limited resection and right lobe adult living
      donor liver transplantation to avoid graft congestion.

PMID- 14648050
TI  - Increased mortality in patients hospitalized with primary hyperparathyroidism
      during the period 1977-1993 in Denmark.
AB  - The aim of the present study was to determine whether patients with the incident
      hospital diagnosis of primary hyperparathyroidism (PHPT) in Denmark during the
      period 1977-1993 had an increased mortality from cardiovascular disease and
      cancer compared to the rest of the Danish population. In a random sample of half
      of the Danish population, all patients with an incident hospital diagnosis of
      PHPT were identified in the National Hospital Patients Register. The mortality in
      the cohort was analyzed and compared with the background population. A cohort of
      1578 patients was identified. Follow-up of 1179 women and 376 men, who did not
      die in the same month as the incident PHPT diagnosis, was made through 1993. Of
      these, 312 (20%) died within the follow-up period. The standard mortality ratio
      (SMR) for women was 1.7 (95% confidence interval [95% CI]: 1.5-1.9). SMR for men
      was 1.6 (95% CI: 1.3-2.0). In women an increased mortality from ischemic heart
      disease, cerebrovascular disease, and cancer was found. In men an increased
      mortality from cerebrovascular disease and cancer was found.

PMID- 14648054
TI  - A screening procedure for prioritizing riparian management.
AB  - A spatially explicit linear, additive model was developed for quantifying site
      characteristics of riparian areas of the lower Cedar River, Washington, USA. The
      spatial complexity and distribution of combined habitat and anthropogenic
      landscape features were used to define habitat "indices" that indicate the
      relative quality of riparian habitats. Patches of contiguous grid cells were
      measured in terms of their locations, sizes, and relative degree of
      fragmentation. Additionally, intrapatch heterogeneity was measured to identify
      unique combinations of habitat and anthropogenic factors for individual grid
      cells within patches. Model verification indicated that existing floodplain
      riparian habitats received positive indices more than 90% of the time. Mean patch
      sizes and fragmentation indices were similar for all positive indices throughout
      the reaches in the valley floor. Among all reaches, reach 7 had the highest
      number of positive patches due to a higher degree of meandering in this reach.
      This procedure and model outputs provide unique screening opportunities for
      prioritizing management of riparian areas (e.g., conservation, restoration and
      enhancement).

PMID- 14648062
TI  - A new paradigm for the aging Asian face.
AB  - Traditionally, Asians have been thought to age more gracefully than Caucasians.
      The resistance to aging in the Asian patient was credited to the thicker dermis
      of Asian skin that contains greater collagen and the darker pigment that protects
      against photoaging. Although these statements are true, the authors propose a new
      paradigm that explains how the illusion of Asian youthfulness may be understood.
      The "baby model" purports that the Asian face has many attributes similar to an
      infant, including a wider and rounder face, higher eyebrow, fuller upper lid,
      lower nasal bridge, flatter midface, apparently more protuberant lips, and more
      receded chin. These commonalities between the infant and the Asian compel the
      viewer to perceive the Asian face as more youthful. However, the Asian face is
      subjected to a greater amount of gravitational force due to weaker skeletal
      support, heavier soft tissue, larger amount of malar fat, thicker skin, and a
      weaker chin. Facial rejuvenative surgery should always be cognizant of the
      propensity of the Asian skin to unfavorable healing, need for greater tissue
      suspension, and more conspicuous temporal alopecia. Asian aesthetics that differ
      and converge with Western ideals are reviewed so that the Western surgeon in
      particular can comprehend the Asian conception of youthful beauty.

PMID- 14648063
TI  - Brow or forehead fixation with sutures only: a preliminary communication.
AB  - Fixation of the brow, although not technically difficult, can be a time-consuming
      process. Screws, whether permanent or absorbable, are occasionally associated
      with minor undesirable problems. We present a technique of brow suspension that
      is quick, simple, and free of the problems associated with fixation to the
      calvarium. It involves the use of sutures only. A heavy PDS suture is passed
      (with the aid of an awl) from the dermis of the brow or forehead that needs to be
      fixed to the dermis of a small incisional wound located 5-8 cm away. This suture
      suspension technique has proven to be quick and easy to execute. It has provided
      satisfactory fixation of the forehead/brow without problems of suture reaction.
      The cost of calvarial screws has been eliminated. When brow or forehead fixation
      is necessary, suspension with sutures to the dermis of a more superior location
      is an excellent method to accomplish the task quickly and easily. Long-term
      follow-up of a large series of patients will be necessary to validate the initial
      impression of this new technique.

PMID- 14648064
TI  - Human histology and persistence of various injectable filler substances for soft
      tissue augmentation.
AB  - An increasing number of soft tissue filler substances have been introduced to the
      beauty market outside the U.S. which lack experimental and clinical data in
      support of their claim. Ten commercially available filler substances were
      examined for biocompatibility and durability: 0.1 cc of each substance was
      injected deep intradermally into the volar forearm of one of the authors and
      observed for clinical reaction and permanence. At 1, 3, 6, and 9 months the test
      sites were excised, histologically examined, and graded according to foreign body
      reactions classification. Collagen (Zyplast) was phagocytosed at 6 months and
      hyaluronic acid (Restylane) at 9 months. PMMA microspheres (Artecoll) had
      encapsulated with connective tissue, macrophages, and sporadic giant cells.
      Silicone oil (PMS 350) was clinically inconspicuous but dissipated into the
      tissue, causing a chronic foreign body reaction. Polylactic acid microspheres
      (New-Fill) induced a mild inflammatory response and had disappeared clinically at
      4 months. Dextran microspheres (Reviderm intra) induced a pronounced foreign body
      reaction and had disappeared at 6 months. Polymethylacrylate particles
      (Dermalive) induced the lowest cellular reaction but had disappeared clinically
      at 6 months. Polyacrylamide (Aquamid) was well tolerated and remained palpable to
      a lessening degree over the entire testing period. Histologically, it dissipated
      more slowly and was kept in place through fine fibrous capsules.
      Polyvinylhydroxide microspheres suspended in acrylamide (Evolution) were well
      tolerated, slowly diminishing over 9 months. Calcium hydroxylapatite microspheres
      (Radiance FN) induced almost no foreign body reaction but were absorbed by the
      skin at 12 months. Host defense mechanisms react differently to the various
      filler materials, but all substances-resorbable or nonresorbable-appeared to be
      clinically and histologically safe, although all exhibit undesirable side
      effects. Since the mechanism of late inflammation or granuloma formation is still
      unknown, early histological findings are not useful in predicting possible late
      reactions to filler substances.

PMID- 14648065
TI  - Improved scar quality following primary and secondary healing of cutaneous
      wounds.
AB  - Poor wound healing remains a critical problem in our daily practice of surgery,
      exerting a heavy toll on our patients as well as on the health care system. In
      susceptible individuals, scars can become raised, reddish, and rigid, may cause
      itching and pain, and might even lead to serious cosmetic and functional
      problems. Hypertrophic scars do not occur spontaneously in animals, which
      explains the lack of experimental models for the study of pathologic scar
      modulation. We present the results of three clinical comparative prospective
      studies that we have conducted. In the first study, secondary healing and
      cosmetic appearance following healing of partial thickness skin graft donor sites
      under dry (semi-open Sofra-Tulle dressing) and moist (moist exposed burn
      ointment, MEBO) was assessed. In the second study, healing of the donor sites was
      evaluated following treatment with Tegaderm or MEBO, two different types of
      moisture-retentive dressings. In the third study, 3 comparable groups of
      primarily healed wounds were evaluated. One group was treated by topical
      antibiotic ointment, the second group was treated by Moist Exposed Burn Ointment
      (MEBO), and the third group did not receive any topical treatment. In the second
      study, secondary healing of partial thickness skin graft donor sites was
      evaluated following treatment with Tegaderm or MEBO, two different types of
      moisture-retentive dressings. In the second and third studies, healed wounds were
      evaluated with the quantitative scale for scar assessment described by Beausang
      et al. Statistical analysis revealed that for both types of wound healing, scar
      quality was significantly superior in those wounds treated with MEBO.

PMID- 14648067
TI  - Heated tumour cells of autologous and allogeneic origin elicit anti-tumour
      immunity.
AB  - Vaccination with established tumour cell lines may circumvent the problem of
      obtaining autologous tumour cells from patients, but may also need immunological
      adjuvants. Up-regulation of heat shock proteins within tumour cell vaccines has
      resulted in increased immunogenicity in some models, but this has yet to be
      demonstrated for allogeneic (MHC-disparate) cell vaccines. This was investigated
      here using a rat model for prostate tumour cell vaccination. Heating of tumour
      cells (42 degrees C, 1 h) elicited significant increases in HSP70 expression.
      Vaccination with heated autologous PAIII cells elicited protection against PAIII
      challenge in 60% of rats >50 days compared to 0% with unheated vaccine and was
      associated with an increased Th1 (IFNgamma) immune response. Heated allogeneic
      MLL cells elicited significant protection against PAIII challenge, in contrast to
      unheated cells. The principle was confirmed in two mouse models, although the
      allogeneic melanoma vaccine K1735 elicited the best protection when heated and
      administered mixed with autologous dendritic cells. Thus, while heating of
      vaccine cells in some models is highly beneficial, and is a means of enhancing
      immunogenicity without genetic modification or inclusion of potentially toxic
      adjuvants, additional immune enhancement may be required.

PMID- 14648068
TI  - Characteristics of the killing mechanism of human natural killer cells against
      hepatocellular carcinoma cell lines HepG2 and Hep3B.
AB  - PURPOSE: Unlike normal hepatocytes, most hepatocellular carcinomas (HCCs) are
      quite resistant to death receptor-mediated apoptosis when the cell surface death
      receptor is cross linked with either agonistic antibodies or soluble death ligand
      proteins in vitro. The resistance might play an essential role in the escape from
      the host immune surveillance; however, it has not been directly demonstrated that
      HCCs are actually resistant to natural killer (NK) cell-mediated death.
      Therefore, this study investigated the molecular mechanism of NK cell-mediated
      cytotoxicity against the HCCs, HepG2, and Hep3B, using two distinct cytotoxic
      assays: a 4-h (51)Cr-release assay and a 2-h [(3)H] thymidine release assay which
      selectively measures the extent of necrotic and apoptotic target cell death,
      respectively. METHODS: Most of the target cells exhibited marked morphologic
      changes when they were co-incubated with the NK cells, and the NK cytotoxicity
      against these HCCs was comparable to that against K562, a NK-sensitive leukemia
      cell line, when the cytotoxicity was assessed by a 4-h (51)Cr release assay.
      RESULTS: The NK cells also induced significant apoptotic cell death in the Hep3B
      targets, but not in the HepG2 targets, when the cytotoxicity was assessed by a 2
      h [(3)H]-thymidine release assay. In agreement with these results, procaspase-3
      was activated in the Hep3B targets, but not in the HepG2 targets. Interestingly,
      mildly fixed NK cells had no detectable activity in the 4-h (51)Cr release assay
      against both HepG2 and Hep3B targets, while they were similarly effective as the
      untreated NK cells in the 2-h [(3)H]-thymidine release assay, suggesting that the
      level of apoptotic cell death of the Hep3B targets is granule independent and
      might be primarily mediated by the death ligands of the NK cells. CONCLUSION:
      This study found that a tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand TRAIL)/TRAIL receptor interaction is involved in the NK cell-mediated
      apoptotic death of the Hep3B targets, but a Fas/Fas ligand (FasL) interaction is
      not.

PMID- 14648069
TI  - Clinical applications of dendritic cell vaccination in the treatment of cancer.
AB  - Dendritic cell (DC) immunotherapy has shown significant promise in animal studies
      as a potential treatment for cancer. Its application in the clinic depends on the
      results of human trials. Here, we review the published clinical trials of cancer
      immunotherapy using exogenously antigen-exposed DCs. We begin with a short review
      of general properties and considerations in the design of such vaccines. We then
      review trials by disease type. Despite great efforts on the part of individual
      investigative groups, most trials to date have not yielded data from which firm
      conclusions can be drawn. The reasons for this include nonstandard DC preparation
      and vaccination protocols, use of different antigen preparations, variable means
      of immune assessment, and nonrigorous criteria for defining clinical response.
      While extensive animal studies have been conducted using DCs, optimal parameters
      in humans remain to be established. Unanswered questions include optimal cell
      dose, use of mature versus immature DCs for vaccination, optimal antigen
      preparation, optimal route, and optimal means of assessing immune response. It is
      critical that these questions be answered, as DC therapy is labor- and resource
      intensive. Cooperation is needed on the part of the many investigators in the
      field to address these issues. If such cooperation is not forthcoming, the
      critical studies that will be required to make DC therapy a clinically and
      commercially viable enterprise will not take place, and this therapy, so
      promising in preclinical studies, will not be able to compete with the many other
      new approaches to cancer therapy presently in development. Trials published in
      print through June 2003 are included. We exclude single case reports, except
      where relevant, and trials with so many variables as to prevent interpretation
      about DC therapy effects.

PMID- 14648070
TI  - Phase 1B study to improve immune responses in head and neck cancer patients using
      escalating doses of 25-hydroxyvitamin D3.
AB  - Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune
      defects. These defects are associated with a poor prognosis and are mediated, in
      part, by immune inhibitory CD34(+) progenitor cells, whose numbers are increased
      in the peripheral blood of HNSCC patients. Immune inhibitory CD34(+) cells are
      also present within HNSCC tumors. A phase IB clinical trial was conducted with
      HNSCC patients to determine if treatment with the differentiation-inducer 25
      hydroxyvitamin D(3) could diminish CD34(+) cell levels and improve a panel of
      immune parameters. Here we present the results of treatment with orally
      administered escalating doses (20, 40, 60 microg) of 25-hydroxyvitamin D(3), with
      an emphasis on the six patients who received the maximum dosage of 60 microg per
      day. Peripheral blood was collected at 0, 1, 2, 4, and 6 weeks, and assessed for
      markers of immune activity. Although no clinical responses were observed, results
      of this pilot study demonstrated that treatment of HNSCC patients with 25
      hydroxyvitamin D(3 )reduces the number of immune suppressive CD34(+) cells,
      increases HLA-DR expression, increases plasma IL-12 and IFN-gamma levels, and
      improves T-cell blastogenesis. In contrast, 25-hydroxyvitamin D(3) treatment did
      not modulate plasma IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, or TGF-beta
      levels.

PMID- 14648071
TI  - A highly effective and stable bispecific diabody for cancer immunotherapy: cure
      of xenografted tumors by bispecific diabody and T-LAK cells.
AB  - PURPOSE: In the field of cancer immunotherapy research, the targeting of effector
      cells with specific antibodies is a very promising approach. Recent advances in
      genetic engineering have made it possible to prepare immunoglobulin fragments
      consisting of variable domains using bacterial expression systems. METHODS: We
      have produced an anti-epidermal growth-factor receptor (EGFR) x anti-CD3
      bispecific diabody (Ex3 diabody) in an Escherichia coli (E. coli) expression
      system with refolding method. The Ex3 diabody targets lymphokine-activated killer
      cells with a T-cell phenotype (T-LAK cells) to EGFR positive bile duct carcinoma
      cells with dramatic enhancement of cytotoxicity in vitro. This specific killing
      of EGFR-positive cells was completely inhibited by parental mAb IgGs directed to
      EGFR and the CD3 antigen. RESULTS: When T-LAK cells were cultured with EGFR
      positive tumor cells in the presence of Ex3 diabody, they produced much higher
      levels of IFN-gamma, GM-CSF, and TNF-alpha than in its absence, this being a
      possible mechanism underlying specific antitumor activity. The Ex3 diabody showed
      good stability when tested at 37 degrees C for 48 h, and also markedly inhibited
      tumor growth of bile duct carcinoma xenografts in severe combined immunodeficient
      (SCID) mice. When Ex3 diabody (20 microg/mouse) was administrated intravenously,
      together with T-LAK cells and interleukin-2 (IL-2), complete cure of tumors were
      observed in three of six mice, and the other three showed marked retardation of
      tumor growth. CONCLUSION: The Ex3 diabody can be considered a highly promising
      reagent for study of specific targeting immunotherapy against bile duct and other
      EGFR-positive carcinomas.

PMID- 14648072
TI  - Safety and efficacy of locally applied imiquimod cream 5% for the treatment of
      condylomata acuminata of the vulva.
AB  - AIM: The aim of the present study was to assess the efficacy and safety of local
      application of imiquimod cream 5% for managing condylomata acuminata of the vulva
      in women referred to a tertiary University Hospital centre. METHOD: From a total
      of 283 patients referred over a 3-year period, 73(26%) were treated with
      imiquimod. RESULTS: Approximately 6% failed to continue therapy due to lack of
      therapeutic effect whereas 71% experienced total clearance of the lesions and 85%
      reduction of more than 50% in the size of the condylomata. Forty-three percent of
      the patients observed complete response in the first 6 weeks of therapy. There
      were no serious adverse events encountered with mild erythema being the
      commonest. From the patients who were followed-up for the next 12 weeks from the
      completion of treatment, 13% presented recurrent warts and were managed by a
      different mode of therapy. CONCLUSION: Imiquimod cream 5% seems to be an
      effective and safe method for treating condylomata acuminata of the vulva
      resulting possibly in lower recurrence rates than other current therapies.

PMID- 14648073
TI  - Short-term calcium supplementation has no effect on biochemical markers of bone
      remodeling in early postmenopausal women.
AB  - INTRODUCTION: This study was designed to assess changes in biochemical markers of
      bone remodeling in early postmenopausal women receiving calcium supplementation.
      MATERIALS AND METHODS: In a randomized cross-over study of eighteen weeks
      duration, the effect of a 6-week calcium supplementation (1000 mg calcium
      carbonate) on biochemical markers of bone resorption (collagen type I cross
      linked C- and N-telopeptides) and bone formation (osteocalcin, total and bone
      specific alkaline phosphatase), and total serum calcium was assessed in 27 early
      postmenopausal women. RESULTS: While total serum calcium levels increased
      significantly due to calcium supplementation (p<0.05), biochemical markers of
      both bone resorption and formation remained virtually unchanged. CONCLUSION: In
      contrast to other investigations, there was no significant short-term effect of
      calcium supplementation on biochemical markers of either bone resorption or
      formation.

PMID- 14648074
TI  - Effect of 17beta-estradiol on immunosuppression induced by ultraviolet B
      irradiation.
AB  - BACKGROUND: The risk of skin cancer is lower in females than in males, and
      photoimmunosuppression caused by ultraviolet (UV) radiation is thought to be
      involved in the progression of skin cancer. OBJECTIVES. To determine the effect
      of 17beta-estradiol on immunosuppression and contact hypersensitivity (CHS)
      caused by ultraviolet B (UVB) irradiation. METHODS: Systemic immunosuppression
      was induced in C57BL mice that had been sensitized with 0.5% fluorescein
      isothiocyanate (FITC) through the skin by a single exposure to UVB (10 kJ/m2).
      The CHS response was assessed after applying FITC to mice treated
      intraperitoneally with 17beta-estradiol, tamoxifen (17beta-estradiol antagonist),
      or antiestradiol antibody. Levels of serum interleukin-10 (IL-10) were measured
      in treated mice and control mice using an enzyme-linked immunosorbent assay
      (ELISA). To assess the effect of 17beta-estradiol on keratinocytes, Pam-212 cells
      were exposed in vitro to UVB radiation and treated for 24 h with 17beta
      estradiol. The IL-10 content of the supernatant was measured using an ELISA.
      RESULTS: The CHS response in UVB-irradiated mice was significantly suppressed in
      comparison to that in nonirradiated mice. Consecutive intraperitoneal injections
      of 17beta-estradiol significantly reduced UVB-induced suppression of the CHS
      response in male mice, whereas injection of tamoxifen or antiestradiol antibody
      significantly promoted UVB-induced suppression in female mice. Treatment with
      17beta-estradiol decreased the serum IL-10 levels in CHS-suppressed male mice
      after UVB irradiation, but treatment with tamoxifen or antiestradiol antibody
      increased the serum IL-10 levels in female mice. Treatment with 17beta-estradiol
      reduced IL-10 production by UVB-irradiated Pam-212 cells in a dose-dependent
      manner. CONCLUSIONS: These results suggest that 17beta-estradiol prevents UVB
      induced suppression of the CHS response caused by immunosuppressive cytokines
      produced by keratinocytes.

PMID- 14648075
TI  - Successful treatment of axillary hyperhidrosis with very low doses of botulinum
      toxin B: a pilot study.

PMID- 14648076
TI  - Alpha-synuclein in motor neuron disease: an immunohistologic study.
AB  - Alpha-synuclein (ASN) has been implicated in neurodegenerative disorders
      characterized by Lewy body inclusions such as Parkinson's disease and dementia
      with Lewy bodies. Lewy body-like inclusions have also been observed in spinal
      neurons of patients with amyotrophic lateral sclerosis (ALS) and reports suggest
      possible ASN abnormalities in ALS patients. We assessed ASN immunoreactivity in
      spinal and brain tissues of subjects who had died of progressive motor neuron
      disorders (MND). Clinical records of subjects with MND and a comparison group
      were reviewed to determine the diagnosis according to El-Escariol Criteria of
      ALS. Cervical, thoracic and lumbar cord sections were stained with an antibody to
      ASN. A blinded, semiquantitative review of sections from both groups included
      examination for evidence of spheroids, neuronal staining, cytoplasmic inclusions,
      anterior horn granules, white and gray matter glial staining, corticospinal tract
      axonal fiber and myelin changes. MND cases, including ALS and progressive
      muscular atrophy, displayed significantly increased ASN staining of spheroids (
      P< or =0.001), and glial staining in gray and white matter ( P< or =0.05).
      Significant abnormal staining of corticospinal axon tract fibers and myelin was
      also observed ( P< or =0.05 and 0.01). Detection of possible ASN-positive
      neuronal inclusions did not differ between groups. Significant ASN abnormalities
      were observed in MND. These findings suggest a possible role for ASN in MND;
      however, the precise nature of this association is unclear.

PMID- 14648077
TI  - Histological evidence of redox system breakdown caused by superoxide dismutase 1
      (SOD1) aggregation is common to SOD1-mutated motor neurons in humans and animal
      models.
AB  - Living cells produce reactive oxygen species (ROSs). To protect themselves from
      these ROSs, the cells have developed both an antioxidant system containing
      superoxide dismutase 1 (SOD1) and a redox system including peroxiredoxin2 (Prx2,
      thioredoxin peroxidase) and glutathione peroxidase1 (GPx1): SOD1 converts
      superoxide radicals into hydrogen peroxide (H2O2), and H2O2 is then converted
      into harmless water (H2O) and oxygen (O2) by Prx2 and GPx1 that directly regulate
      the redox system. To clarify the biological significance of the interaction of
      the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we
      produced an affinity-purified rabbit antibody against Prx2 and investigated the
      immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like
      hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral
      sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-
      >Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats
      expressing human SOD1 with H46R and G93A mutations. The LBHIs in motor neurons
      from the SOD1-mutated FALS patients and transgenic rats showed identical
      immunoreactivities for Prx2 and GPx1: the reaction product deposits with the
      antibodies against Prx2 and GPx1 were localized in the LBHIs. In addition, the
      localizations of the immunoreactivities for SOD1 and Prx2/GPx1 were similar in
      the inclusions: the co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs in
      mutant SOD1-related FALS patients and transgenic rats was evident. Based on the
      fact that Prx2/GPx1 directly regulates the redox system, such co-aggregation of
      Prx2/GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the redox
      system itself, thereby amplifying the mutant SOD1-mediated toxicity in mutant
      SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1.

PMID- 14648078
TI  - Immunohistochemical analysis of protein expression after middle cerebral artery
      occlusion in mice.
AB  - The effect of transient focal cerebral ischemia on protein regulation was studied
      in mice using multiparametric immunohistochemistry. Injury was characterized by
      measurements of blood flow, regional protein synthesis and terminal transferase
      biotinylated-dUTP nick end labeling (TUNEL). The proteins studied were selected
      from a previously established list of differentially regulated proteins and
      included the GTPases dynamin, RhoB, CAS and Ran BP-1, the transcription factors
      Nurr1 and p-Stat 6, the protein kinase MAPK p49, the splicing factors SRPK1 and
      hPrp16, the cell cycle control proteins cyclin B1 and Nek2, the inflammatory
      proteins FKBP12 and Rag2, the cell adhesion protein paxillin and the folding
      protein TCP-1. Regulation patterns were diverse and comprised ipsi- and/or
      contralateral up- and down-regulation with or without topical association to
      impeding cell death. Some proteins (SRPK1, TCP-1 and Nurr1) also exhibited post
      ischemic translocation from the nucleus to the cytosol. Our observations stress
      the importance of regional analysis for the interpretation of proteomic data, and
      contribute to the identification of new pathways that may be involved in the
      evolution of post-ischemic brain injury.

PMID- 14648079
TI  - [Overview of the program of the 6th Workshop of the Professional Society of
      Regional Cooperative Rheumatism Centers].

PMID- 14648080
TI  - [Patient education in rheumatology-an overview].
AB  - Patients with rheumatic diseases need a comprehensive and interdisciplinary
      treatment. In this context patient education takes the part to lead patients to a
      better self-management. The goals of patient education are the increase of
      knowledge and introspection, the positive influencing of attitudes and self
      efficacy and in addition the improvement of disease or health behavior. It is
      well known that the necessary change of behavior is hard and depends on various
      conditions. The study group "patient education" of the German Society of
      Rheumatology had developed several education programs, the methods and topics of
      which are based on behavioral science. These programs are topic centered and
      close to patients' needs. Their efficacy has been proved on different levels,
      economic advantages have been shown. At present these programs are mostly used
      for inpatients. Since there is no payment to implement these programs for
      outpatients, alternative ways are necessary.

PMID- 14648081
TI  - [Patient education in rheumatology-The current situation].
AB  - The article summarizes the state of the art in patient education in rheumatology
      and describes the goals that have been reached and the problems that have to be
      solved in the future. Within recent years 6 patient education programs have been
      developed, 4 additional programs are in progress. Evaluation studies have been
      conducted for 3 programs showing evidence for the efficacy of patient education
      in different fields. Furthermore quality standards for patient education in
      rheumatology have been worked out and train-the-trainer-seminars are held
      regularly. Most of the activities in patient education take place in inpatient
      settings because of the lack of financial support for patient education courses
      in outpatient settings. Therefore future efforts have to concentrate on
      negotiations with health insurance companies to obtain money for running
      comprehensive outpatient education courses overall in Germany.

PMID- 14648082
TI  - [Costs and benefits of an education program for patients with ankylosing
      spondylitis as part of an inpatient rehabilitation programs-study design and
      first results].
AB  - The economic evaluation of a patient education program "ankylosing spondylitis"
      based on a randomised controlled prospective multi-center study design-compares
      program costs and savings in direct and indirect follow-up costs. The collection
      of health services and cost data was conducted by questioning staff (education
      programme costs) and patients (follow-up costs). The present study results are:
      program costs per patient range between 117 euro (10 participants per course) and
      186 euro (6 participants per course). Savings in indirect costs (unfitness to
      work) amount to 2500 euro and thus overcompensate program costs. Currently
      patient data are verified by sickness fund data and direct follow-up costs and
      qualitiy of life data are analysed.

PMID- 14648083
TI  - [A new patient education program: vasculitis].
AB  - Referring to the literature it is known that structured standardized patient
      education represents an effective additional treatment in patients with chronic
      diseases. Programs base on cognitive behavioral interventions. Within the last
      years an interdisciplinary approach for providing information on disease,
      therapies, side effects, coping strategies, nutrition and physiotherapy has been
      developed for patients with primary systemic vasculitides (PSV) in the vasculitis
      center Medical University of Luebeck/Bad Bramstedt. The contents of the seminars
      were revised and condensed into five modules. To evaluate the new program a
      documentation system consisting of patient and physician- administered
      questionnaires assessing socioeconomic, knowledge and disease-related outcome
      parameters has been designed. Patients completed the questionnaires at baseline,
      4 weeks, 6 and 12 months after training. First results show statistically
      significant improvement of knowledge and health-related quality of life.

PMID- 14648084
TI  - [Quality standards and certification of patient education in rheumatology].
AB  - Patient education includes much more than only explanation or information
      regarding illness. The intention of all is to have a positive influence on
      patients' behaviour and to deliver the capability of self-management. One has to
      understand that the development and the realization of those programme needs a
      high quality level to achieve a reasonable result. The quality standards have
      been worked out by the DGRh-commission "Patientenschulung"-demonstrating the
      different levels of patient education. These standards are the basics of
      certificate and also the prerequisite to negotiate about the costs of patient
      education with the health insurance.

PMID- 14648085
TI  - [Patient education "systemic sclerosis"].
AB  - We report on the development of an education program for patients with systemic
      sclerosis. The program was developed by a multi professional group in cooperation
      with scleroderma patients and the scleroderma patient organization. Patient
      education will be carried out by professional trainers as a weekend seminar
      within a group of 6 to 12 participants according to the method of subject
      focussed interaction. The program consisting of 7 modules is now in the final
      test phase.

PMID- 14648086
TI  - [Qualification via training courses].
AB  - Patient education includes cognitive parts as well as coping aspects and learning
      new skills. Therefore it is necessary to prepare the interdisciplinary training
      team for their tasks. The German Society of Rheumatology offers special training
      courses for these tasks. The training courses are divided into a basic seminar
      and a seminar for special education programs. The basic seminar will mediate
      knowledge and increase skills used in patient education. Conceptions,
      effectiveness and advantages are shown. Information and experiences specially
      mixed with exercises in the areas of communication, group dynamics and adult
      education take place. In the seminar for special education programs information
      about this program and its specific problems is given. In addition participants
      have the possibility to discuss their experiences.

PMID- 14648087
TI  - [Patient education in practice-a workshop in a small group].
AB  - The aim of the workshop was to work out concrete plans and steps for implementing
      patient education courses in an outpatient setting by the collaborative arthritis
      centers in Germany. Primarily the patient education model of Lower Saxony was
      illustrated as an example of successful implementation of patient education
      programs in practice. In this state patient education courses are run in
      cooperation between the Arthritis Center of Hannover and the League against
      Rheumatism in Lower Saxony. Both institutions are in discussion with the health
      insurance companies for paying the costs for the patient education courses. Then
      the group discussed several important aspects which have to be considered when
      establishing patient education courses such as recruiting and motivating the
      trainers, recruiting the participants, choosing adequate rooms, fund raising and
      responsibilities. The participants considered the patient education model of
      Lower Saxony as a transferable model for every collaborative arthritis center in
      Germany and recommended to follow that path.

PMID- 14648088
TI  - [Molecular imaging in rheumatoid arthritis].
AB  - Advances in molecular biology and technical developments in the field of imaging
      are increasingly allowing for non-invasive visualization and quantitation of
      biological processes at the molecular level. Such technologies, defined as
      molecular imaging, promise early diagnosis and improved classification of the
      stage and severity of disease, objective assessment of treatment efficacy, and
      reliable prognosis based on so-called molecular markers. Furthermore, molecular
      imaging is an important tool for the evaluation of physiological and
      pathophysiological processes and for drug development. Various different imaging
      modalities are available, such as conventional radiography (CR), computed
      tomography (CT), nuclear imaging, magnetic resonance imaging (MRI), ultrasound
      (US), as well as other methods including fluorescence-based optical imaging.
      These methods differ with respect to resolution and their potential to gather
      information at the anatomical, physiological, cellular and molecular level.
      Therefore, the choice of the imaging modality for molecular imaging depends on
      the questions that need to be answered. This review discusses the potential of
      imaging modalities for molecular imaging in rheumatoid arthritis (RA).

PMID- 14648089
TI  - [Imaging beyond conventional radiography: mini arthroscopy, duplex
      ultrasonography and positron emission tomography].
AB  - Imaging procedures, such as ultrasound and magnetic resonance imaging have
      broadened the diagnostic spectrum by "visualization" of pathomorphologic changes
      in rheumatic diseases. The advantages of these techniques are sectional imaging
      and three dimensional illustration, which enhance the exact detection of
      inflammatory soft tissue alterations and the sensitive and early detection of
      bony changes. Most current techniques and methods such as mini arthroscopy, color
      and power Doppler ultrasonography and positron emission tomography (PET) complete
      the set of diagnostic tools for rheumatologists, when other diagnostics reach
      their limits. Doppler ultrasonography and PET detect and assess inflammatory
      changes of systemic diseases locally and on the whole, which were not visible by
      standard diagnostic procedures. Mini arthroscopy furnishes, besides the direct
      evaluation of the joint, access to the pathomorphologic substrate itself with the
      opportunity of tissue sampling and further molecular biological analysis. These
      new diagnostic techniques open a widespread goal for rheumatologists in terms of
      etiopathogenesis, early diagnosis and monitoring of inflammatory rheumatic
      diseases.

PMID- 14648090
TI  - [Informing patients in the German Rheumaliga].
AB  - The German Rheuma-Liga as the largest patient organisation presents the different
      ways of informing patients. Patient- education-programs are presented, with a
      program focussing on social and psychological issues in particular.

PMID- 14648091
TI  - [Hypoxia and angiogenesis in rheumatic diseases].
AB  - The important role of angiogenesis for the pathogenesis of most tumors has gained
      much interest into the mechanisms of new vessel formation during recent years.
      Hypoxia induces angiogenesis via stabilization of the transcription factor HIF
      1alpha. After dimerization of HIF-1alpha with HIF-1beta/ARNT, HIF-1 binds to the
      hypoxia-responsive elements in the regulatory regions of proangiogenic molecules
      such as VEGF. Hypoxia-mediated angiogenesis also plays a part in the pathogenesis
      of rheumatoid arthritis. For instance, intraarticular application of the
      angiostatic molecule angiostatin reduces the severity of collagen-induced
      arthritis in mice. Moreover, recent data indicate that the expression of HIF
      1alpha in myeloid cells is important for the initiation of the inflammatory
      infiltrate in rheumatoid arthritis. In contrast to rheumatoid arthritis, the
      therapeutic goal in systemic sclerosis (SSc) is the formation of new vessels
      rather than the inhibition of angiogenesis. Surprisingly, several proangiogenic
      factors such as VEGF or MCP-1 (CCL-2) are overexpressed in the skin of patients
      with SSc despite the reduction in the capillary density. The role of these
      findings for the defective angiogenesis in SSc is currently investigated in our
      laboratory.

PMID- 14648092
TI  - [Tissue engineering: chances and challenges for application in rheumatic
      diseases].
AB  - Current technologies of tissue engineering offer new strategies for the treatment
      of cartilage and bone defects. Beyond implantation of cell suspensions, second
      generation products of biomaterial enforced with in vitro preformed tissues are
      clinically applied. Ongoing research and development focus on differentiation
      factors and tissue protection. In search for sources of autologous cells which
      are easier to collect and which may serve for more complex tissues like
      osteochondral implants, mesenchymal stem cells are investigated. The design of in
      vitro experiments, which are required for these investigations, has produced
      tissue engineering technologies, which may serve for pathophysiology research in
      inflammatory joint diseases and for exploration of treatment strategies. These
      together with the advances in biological therapies of rheumatic diseases are the
      basis of new concepts, which promise application of tissue engineering also in
      inflammatory joint diseases.

PMID- 14648093
TI  - [Innovations in total knee arthroplasty].
AB  - The development of total knee arthroplasty started in the fifth decade last
      century. Modern total knee joint systems represent a high grade of modularity for
      a usage within the whole range of joint destruction situations, such as for
      rheumatoid arthritis. Innovations for improved long term survival can be seen in
      methods reducing aseptic loosening, such as new implant materials or mobile
      platforms. Moreover improved surgical techniques for precise component
      orientation and reconstruction of a neutral leg axis have been introduced using
      computer assisted surgery. So far the results using this technique are very
      promising. Long term results are not yet available.

PMID- 14648094
TI  - [Solutions for off-label therapy].
AB  - About 25% of administrations are for off-label indications. The treatment of many
      rheumatic diseases includes off-label use. Reimbursement from the health
      insurance is possible if no other approved therapy is available, and if
      scientific studies prove the effectiveness of the drug.

PMID- 14648095
TI  - Establishment of a colonic adenoma cell line (GEKI-2): spectral karyotype
      analysis and functional characterization.
AB  - BACKGROUND AND AIMS: On the genetic level colonic carcinogenesis is best
      described by the adenoma-carcinoma sequence, but it may be modulated by exogenous
      factors, particularly by dietary factors and chemopreventive agents. The
      protective effects of exogenous factors are thought to be exerted rather in the
      early stages of the adenoma-carcinoma sequence. Thus, an in vitro model
      consisting of cells stemming from an colon adenoma would be desirable. However,
      establishing such a cell line has proven difficult. MATERIALS AND METHODS: We
      report the establishment of a colon adenoma cell line. The cells were generated
      from a colon adenoma and propagated as a stable cell line for more than 40
      passages. The cells are microsatellite stable and confirmed to be of epithelial
      origin by cytokeratin staining. RESULTS: In contrast to commercially available
      colon cancer cell lines, cytogenetic analysis with spectral karyotype analysis
      revealed no chromosomal alterations in this adenoma cell line. Incubation with
      butyrate resulted in a time- and dose-dependent inhibition of proliferation and
      in an significant increase in cellular differentiation. The cdk inhibitor p21/waf
      which plays a pivotal role in growth inhibition and differentiation is expressed
      consecutively in GEKI-2 cells. The expression of cdk1 and cdk2, important
      regulatory elements in the cell cycle, is downregulated following treatment with
      butyrate. CONCLUSION: The presented colon adenoma cell line GEKI-2 may prove a
      versatile tool for further exploring the underlying mechanisms of protective and
      promoting factors in early colon cancerogenesis.

PMID- 14648096
TI  - Bladder spasm in children after surgery for ureteric reimplantation.
AB  - The primary aim of this study was to prospectively investigate whether there was
      an association between the duration of post-operative catheterisation and the
      incidence of bladder spasm in children following ureteric reimplantation surgery.
      A secondary aim was to investigate whether other surgical and post-operative
      factors had an effect on the incidence of bladder spasm.

PMID- 14648097
TI  - The use of LigaSure during pediatric laparoscopic splenectomy: a preliminary
      report.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is becoming the gold standard for the
      treatment of hematological disease in children. Intraoperative bleeding is the
      main complication and main cause of conversion during LS. We present the use of
      the LigaSure Vessel Sealing System for achieving a safe vascular control,
      compared with previous techniques. METHODS: LigaSure is an energy-based device
      which works by applying a precise amount of bipolar energy and pressure to the
      tissue, thus achieving a permanent seal. We have performed a total of 15 LS in
      children during 6 years, on 6 males and 9 females with a median age of 11 years
      (range 5-17). Seven children had hereditary spherocytosis, 4 thrombocytopenic
      idiopatic purpura (ITP), 3 beta talassemia, and 1 hemolytic anemia. Patients were
      divided into two groups according to the method of dissection: group 1 ultrasonic
      coagulation+endostapler (8 pts); group 2 LigaSure (7 pts). We employed a 4
      trocars technique with right semilateral position. RESULTS: The groups were well
      matched for age, gender, weight, indication and spleen size. Fourteen LS were
      completed with one conversion (7%) because of hilar bleeding due to accidental
      injury with endostapler. Median operative time of the series was 140 min (range
      90-205), significantly shorter in the group 2 (130 min versus 155 min, P<0.05),
      as well as median blood loss (group 1, 180 ml versus group 2, 70 ml, P<0.05).
      There was no mortality, with one postoperative complication (7%) (pulmonary
      atelectasis). The median postoperative hospital stay was 4 days (range 2-5)
      without differences between groups. CONCLUSIONS: Each method of dissection seems
      to be safe and effective. Otherwise LigaSure results in a reduction of operating
      time and blood loss.

PMID- 14648098
TI  - Split cord malformation and situs inversus totalis: case report and review of the
      literature.
AB  - INTRODUCTION: Situs inversus is a rare condition of visceral transposition in
      which the spinal axis is rarely affected. CASE REPORT: The authors report a
      patient with situs inversus totalis and type II split cord malformation. This
      patient had no complaints and presented with scoliosis. CONCLUSIONS: Recent
      compelling evidence from animal models and human case reports has led to
      hypotheses that defects of the midline and laterality defects (e.g., situs
      inversus) are etiologically related. Confirmation from additional case reports of
      situs inversus and split cord malformation could prove useful in determining a
      genetic locus for split cord malformations or implicating various chemical agents
      that are known to produce situs inversus as potential causative factors in the
      production of split cord malformations.

PMID- 14648099
TI  - Alanine-stimulated exocytosis in Aplysia enterocytes: effect of Na+ transport and
      requirement for actin filaments.
AB  - We used the Aplysia californica intestinal epithelium to investigate the effect
      of alanine-stimulated Na+ absorption on apical membrane exocytosis and whether
      stimulated exocytosis requires intact actin filaments. The fluid-phase marker
      fluorescein dextran was used to determine rates of apical membrane exocytosis. L
      alanine significantly increased apical exocytosis by approximately 30% compared
      to controls, and there is a modest, positive correlation between alanine
      stimulated exocytosis and short-circuit current (ISC). Thus, apical exocytosis is
      modulated to some extent by the magnitude of Na+ and alanine entry across the
      apical membrane. Apical exocytosis is also responsive to virtually any increase
      in Na+ and alanine entry because increments in alanine-stimulated ISC as small as
      1 microA/cm2 stimulated exocytosis. We used D-alanine to determine which
      parameter (sensitivity to transport vs. magnitude of transport) was most
      important in activation of apical exocytosis. D-alanine-stimulated ISC was one
      sixth that of L-alanine, but stimulated exocytosis was only 29% less than that of
      L-alanine. Therefore, the apical exocytic system is more responsive to small
      increases in transport than to the magnitude of transport. Latrunculin A (Lat-A)
      disrupts the actin cytoskeleton and reduced constitutive apical exocytosis by
      approximately 65% and completely abolished alanine-stimulated exocytosis. Hence,
      constitutive exocytosis and alanine-stimulated exocytosis require actin filaments
      for recruitment of vesicles to the apical membrane. During nutrient absorption,
      actin filament-regulated apical exocytosis may represent a negative feedback
      system that modulates apical membrane tension.

PMID- 14648100
TI  - Behavioral analysis of polarization vision in tethered flying locusts.
AB  - For spatial navigation many insects rely on compass information derived from the
      polarization pattern of the sky. We demonstrate that tethered flying desert
      locusts (Schistocerca gregaria) show e-vector-dependent yaw-torque responses to
      polarized light presented from above. A slowly rotating polarizer (5.3 degrees s(
      1)) induced periodic changes in yaw torque corresponding to the 180 degrees
      periodicity of the stimulus. Control experiments with a rotating diffuser, a weak
      intensity pattern, and a stationary polarizer showed that the response is not
      induced by intensity gradients in the stimulus. Polarotaxis was abolished after
      painting the dorsal rim areas of the compound eyes black, but remained unchanged
      after painting the eyes except the dorsal rim areas. During rotation of the
      polarizer, two e-vectors (preferred and avoided e-vector) induced no turning
      responses: they were broadly distributed from 0 to 180 degrees but, for a given
      animal, were perpendicular to each other. The data demonstrate polarization
      vision in the desert locust, as shown previously for bees, flies, crickets, and
      ants. Polarized light is perceived through the dorsal rim area of the compound
      eye, suggesting that polarization vision plays a role in compass navigation of
      the locust.

PMID- 14648101
TI  - Low-frequency distortion product otoacoustic emissions in two species of kangaroo
      rats: implications for auditory sensitivity.
AB  - Low-frequency distortion-product otoacoustic emissions were measured in two
      species of kangaroo rats to test the prediction that a large footdrumming species
      (e.g., Dipodomys spectabilis) would have greater distortion-product otoacoustic
      emission amplitude than a small non-footdrumming species (e.g., Dipodomys
      merriami), indicating better hearing sensitivity at low frequencies. Equal-level
      (65 dB SPL) stimulus tones ( f(1), f(2)), presented over a ( f(1)) range of 200
      1000 Hz, were used to evoke the 2 f(1)- f(2) distortion-product otoacoustic
      emission. Mean 2 f(1)- f(2) levels for D. merriami showed good correspondence to
      previously published audiograms for that species. Mean 2 f(1)- f(2) levels and
      95% confidence intervals indicated species differences below 400 Hz, supporting
      the theory that low-frequency hearing sensitivity is better in large kangaroo rat
      species. These results suggest that the size-related divergence in footdrumming
      behavior may be related to differential auditory sensitivity.

PMID- 14648102
TI  - Occupational exposure and urological cancer.
AB  - Occupational exposure is definitely a major cause of cancer. In the field of
      urology, the urinary bladder is the most important target. A classical cause of
      bladder cancer is exposure to carcinogenic aromatic amines, especially benzidine
      and beta-naphthylamine. Such exposures were related to work places in the
      chemical industry, implying production and processing of classical aromatic
      amines, and in the rubber industry. Occupational bladder cancer has also been
      observed in dyers, painters and hairdressers. Even some occupations with much
      lower exposures to carcinogenic aromatic amines, like coke oven workers or
      workers in the rubber industry after the ban on beta-naphthylamine, are at risk.
      In these occupations, exposure to complex mixtures of substances containing
      combustion products (e.g. polycyclic aromatic hydrocarbons) or nitrosamines is
      common. Renal cell cancer has been observed as an occupational disease in cases
      of very high exposure to trichloroethylene having led to narcotic or prenarcotic
      symptoms. Occupationally related cancers of the prostate or the testes appear
      currently not relevant.

PMID- 14648103
TI  - Genetic polymorphisms and prostate cancer risk.
AB  - The identification of common genetic polymorphisms that influence susceptibility
      to PC would allow an early risk assessment with earlier and therefore potentially
      more effective intervention by chemopreventive means. In this review we focus on
      published case-control studies and meta-analyses of the following polymorphic
      genes that may play a role in etiology of the androgen receptor (AR), the
      prostate-specific antigen (PSA), 5alpha-reductase type II gene (SRD5A2),
      cytochrome P450c17alpha (CYP17), cytochrome P4503A4 (CYP3A4) and a putative
      hereditary PC susceptibility gene, ELAC2.

PMID- 14648104
TI  - The role of interventional radiology in biliary complications after orthotopic
      liver transplantation: a single-center experience.
AB  - This study evaluated interventional radiological experience in the management of
      biliary complications of OLT at the National Cancer Institute of Milan. Seventeen
      patients who had undergone orthotopic liver transplantation in various hospital
      were referred to our unit with biliary complications. Group I consisted of 8
      patients with anastomotic biliary fistula who came to our attention a short time
      after transplantation. Group II consisted of 9 patients with anastomotic
      strictures who came to our attention in a longer period. Two different
      interventional radiological approaches were used: (a) percutaneous transhepatic
      biliary drainage (PTBD) in the presence of fistulas in patients of group I; and
      (b) percutaneous transhepatic biliary drainage combined with dilatation of the
      strictures with a balloon catheter in patients of group II. On the whole
      resolution of the biliary complications was achieved in 13 of the 17 cases
      treated (76.5%), 5 of 8 in group I and 8 of 9 in group II. No secondary stenosis
      after PTBD were observed in group I, whereas two patients of group II needed a
      second dilatation. Percutaneous biliary drainage is indicated as a valid
      treatment in the management of biliary complications, either to allow closure of
      the fistula either to perform balloon dilatation of stenosis.

PMID- 14648105
TI  - Steady-state free precession sequences in myocardial first-pass perfusion MR
      imaging: comparison with TurboFLASH imaging.
AB  - The aim of this study was to compare the image quality of a saturation-recovery
      gradient-recalled echo (GRE; TurboFLASH) and a saturation-recovery SSFP (SR
      TrueFISP) sequence for myocardial first-pass perfusion MRI. Eight patients with
      chronic myocardial infarction and 8 volunteers were examined with a TurboFLASH
      (TR 2.1 ms, TE 1 ms, FA 8 degrees ) and a SR-TrueFISP sequence (TR 2.1 ms, TE 0.9
      ms, FA, 50 degrees ) on a 1.5 T scanner. During injection of 0.05 mmol/kg BW Gd
      DTPA at 4 ml/s, three short axis slices (8 mm) of the left ventricle (LV) were
      simultaneously scanned during breath-hold. Maximum signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR) between infarcted and normal myocardium, and
      percentage signal intensity change (PSIC) were measured within the LV lumen and
      in four regions of the LV myocardium for the three slices separately. For the LV
      lumen, SR-TrueFISP was superior in SNR and PSIC (factor 3.2 and 1.6,
      respectively). Mean maximum SNR, PSIC, and CNR during peak enhancement in the LV
      myocardium were higher for SR-TrueFISP compared with TurboFLASH (factor 2.4,
      1.25, and 1.24, respectively). The SNR was higher in the septal portion of the
      ventricle than in anterior/posterior and lateral regions. The SR-TrueFISP
      provides higher SNR and improves image quality compared with TurboFLASH in first
      pass myocardial perfusion MRI.

PMID- 14648106
TI  - Identification of fungal ( Magnaporthe grisea) stress-induced genes in wild rice
      ( Oryza minuta).
AB  - To identify fungal stress-related genes in wild rice, Oryza minuta, we
      constructed a subtracted library using suppression subtractive hybridization in
      combination with mirror orientation selection. DNA chips containing 960 randomly
      selected cDNA clones were applied by reverse Northern analysis to eliminate false
      positive clones from the library and to prescreen differentially expressed genes.
      In total, 377 cDNA clones were selected on the basis of their signal intensities
      and expression ratios. Sequence analyses of these 377 cDNA fragments revealed
      that 180 of them (47.7%) represented unique genes. Of these 180 cDNAs, 89 clones
      (49.6%) showed significant homologies to previously known genes, while the
      remaining 91 did not match any known sequences. The putative functions of the 180
      unique ESTs were categorized by aligning them with MIPS data. They were
      classified into seven different groups using microarray data-derived expression
      patterns and verified by Northern blotting.

PMID- 14648107
TI  - Changes in the organization of the tubulin cytoskeleton during the early stages
      of Solanum lycopersicoides Dun. protoplast culture.
AB  - Changes in the tubulin cytoskeleton during protoplast culture and plant
      regeneration of Solanum lycopersicoides Dun. were analyzed using an
      immunodetection method. Directly after isolation, four groups of protoplasts were
      distinguished: (1) mononuclear, (2) polynuclear, (3) homogeneous, (4) anuclear.
      The tubulin cytoskeleton of the protoplasts underwent rearrangements, correlating
      to the number and structure of cell nuclei in the protoplast. All protoplast
      groups with the exception of mononuclear were characterized by perturbations in
      the organization of the tubulin cytoskeleton. Anuclear and homogeneous
      protoplasts did not have a tubulin cytoskeleton. Polynuclear protoplasts had
      cortical microtubules, but were not capable of re-forming their original
      arrangement and did not possess a radial or perinuclear cytoskeleton.
      Irregularities in microtubule arrangement of these three groups of protoplasts
      caused their inability to regenerate a cell wall and to divide. Anuclear,
      polynuclear and homogeneous protoplasts were eliminated from the culture.
      Mononuclear protoplasts rearranged their cortical microtubules and reestablished
      the radial and perinuclear tubulin cytoskeleton. Re-formation of the cell
      suspension and subsequent regeneration of plants occurred exclusively from
      mononuclear protoplasts, which were able to regenerate cell walls and to divide.

PMID- 14648108
TI  - Somatic embryogenesis and fertile green plant regeneration from suspension cell
      derived protoplasts of rye ( Secale cereale L.).
AB  - A method for somatic embryogenesis and fertile green plant regeneration from
      suspension cell-derived protoplasts of rye (Secale cereale L. cv. Auvinen) was
      developed. Fast-growing and friable embryogenic calli with a high regeneration
      capacity were induced from immature rye inflorescences using modified MS medium.
      These friable embryogenic calli were used for suspension culture initiation in
      liquid AA medium. A high yield of protoplasts was obtained from suspension cell
      clumps after 3-5 days of subculture. Isolated protoplasts were cultured in KM8p
      medium. The frequency of protoplast cell divisions and colony formations in
      liquid culture medium were similar to those on agarose-solidified medium. Compact
      embryogenic calli were developed from protoplast-derived microcalli in growth
      medium mMS. Approximately 7% of the transferred embryogenic calli produced green
      shoots on N6 regeneration medium. Of 33 green plants, 28 were fertile with normal
      flowering and seed set. The ratio of green and albino plantlets was 1:4. Rye
      protoplast-derived green plants showed normal diploid characters as determined by
      flow cytometer analysis and chromosome counting.

PMID- 14648109
TI  - Spatial and temporal patterns of green fluorescent protein (GFP) fluorescence
      during leaf canopy development in transgenic oilseed rape, Brassica napus L.
AB  - The green fluorescent protein (GFP) holds promise as a field-level transgene
      marker. One obstacle to the use of GFP is fluorescence variability observed
      within leaf canopies. In growth chamber and field experiments, GFP fluorescence
      in transgenic oilseed rape ( Brassica napus) was shown to be variable at each
      leaf position over time and among different leaves on the same plant. A leaf had
      its highest GFP fluorescence after emergence and, subsequently, its fluorescence
      intensity decreased. GFP fluorescence intensity was directly correlated with the
      concentration of soluble protein. The concentration of the genetically linked
      recombinant Bacillus thuringiensis (Bt) cry1Ac endotoxin protein also was
      examined, and GFP fluorescence was positively correlated with Bt throughout
      development. The results show that GFP can be used as an accurate transgene
      marker but that aspects of plant developmental should be taken into account when
      interpreting fluorescence measurements.

PMID- 14648110
TI  - Infliximab in two patients with juvenile ankylosing spondylitis.
AB  - Infliximab, a monoclonal chimeric anti-tumor necrosis factor alpha (anti-TNF
      alpha) antibody, was tried in two patients suffering from severe refractory
      juvenile ankylosing spondylarthritis with disease duration of more than 10 years.
      To assess the response, validated clinical activity parameters were monitored
      prospectively. In both patients, treatment with infliximab at a dosage of 5 mg/kg
      body weight already led to considerable improvement with loss of joint pain the
      day after it was given. Bath Ankylosing Spondylitis Functional Index scores
      decreased from 5.8 to 0 and 7.2 to 1.0 and the Bath Ankylosing Spondylitis
      Disease Activity Index from 2.6 to 1.4 and 9.0 to 1.0. In one patient, the
      response to a single infusion continued for more than 8 months. Because of a
      recurrence of symptoms in intervals of 2 months, the fourth infusion has now been
      given to the second patient, resulting in immediate clinical response. No side
      effects have been noted. Infliximab seems to be a promising agent for treatment
      of active and refractory juvenile ankylosing spondylitis. Controlled studies and
      long-term observations are warranted.

PMID- 14648111
TI  - Synovial membrane enhancement and bone erosion by magnetic resonance imaging for
      prediction of radiologic progression in patients with early rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to determine the prognostic factors related
      to radiographic progression in patients with early rheumatoid arthritis (RA)
      (less than 1 year after onset) undergoing enhanced MRI at entry. METHODS:
      Demographic characteristics, disease duration, and enhanced MRI of the dominant
      wrists were recorded at entry. Duration of morning stiffness, number of swollen
      joints, serum rheumatoid factor (RF), erythrocyte sedimentation rate, C-reactive
      protein (CRP) level, and radiographs of hands and feet (Sharp/van der Heijde
      score) were assessed at each follow-up. Outcome was defined as damage seen on
      radiography. RESULTS: One hundred fourteen patients were followed up for 10
      years. Logistic regression analysis showed that high MRI score, CRP, and RF
      positivity were associated with radiologic progression. The MRI score at baseline
      was a better predictor than CRP level and RF positivity at entry. CONCLUSION: The
      assessment of synovial membrane enhancement and bone erosion by MRI of the wrist
      in early RA is very helpful to predict erosive outcome.

PMID- 14648112
TI  - Neuropathic arthropathy caused by Arnold-Chiari malformation with syringomyelia.
AB  - We report a case of neuropathic arthropathy caused by Arnold-Chiari malformation
      with syringomyelia, with details of the clinical and radiologic aspects. The
      patient had pain and stiffness in his left upper limb. MRI of the left shoulder
      revealed neuropathic arthropathy. Upon examination, his left elbow also had the
      characteristic findings for neuropathic arthropathy. Examination of the spinal
      cord by MRI confirmed Arnold-Chiari malformation associated with syringomyelia.
      Neuropathic arthropathy requires evaluation of the spinal cord to assess for
      occult causal lesions.

PMID- 14648113
TI  - A novel beta-glucosidase in Uromyces fabae: feast or fight?
AB  - Efficient nutrient mobilization is a key element for biotrophic plant parasites
      such as the rust fungi. In the course of a cDNA library screen for elements
      involved in sugar utilization in Uromyces fabae, we identified a sequence with
      homology to beta-glucosidases. Full-length genomic and cDNA clones of the gene,
      termed BGL1, were isolated and sequenced. The BGL1 gene comprises 3,372
      nucleotides, including nine introns. The open reading frame encompasses 2,532
      bases and codes for a polypeptide of 843 amino acids with an apparent molecular
      mass of 92.4 kDa. Analysis of the polypeptide revealed a potential secretion
      signal, indicating an extracellular localization of mature BGL1p (89.8 kDa). BGL1
      seems to be expressed in all stages of growth, including haustoria, the feeding
      structures of rust fungi. In the course of immunolocalization studies, the gene
      product BGL1p was localized in the periphery of intercellular hyphae and
      haustoria. On the basis of sequence homology, the BGL1 gene was identified as a
      fungal beta-glucosidase.

PMID- 14648114
TI  - High-efficiency transformation of the pathogenic yeast Candida parapsilosis.
AB  - A recently developed transformation system for the pathogenic yeast Candida
      parapsilosis opened a venue for studying the biological phenomena of this species
      at the molecular level. However, the standard chemical method yielded only about
      1x10(3) transformants/microg of DNA, which is insufficient for certain types of
      experiment. With the aim of increasing the transformation efficiency, we employed
      two alternative methods for the introduction of plasmids into the recipient
      cells. Whereas biolistics resulted in about 5x10(2) transformants/microg of
      plasmid DNA, electroporation was an order of magnitude more efficient than the
      chemical method. Pretreatment of cells with 100 mM lithium acetate or 10 mM
      dithiothreitol resulted in a 5-fold (5x10(4)) or a 10-fold (1x10(5)) increase in
      transformation efficiency, respectively. This high-efficiency transformation
      method should be suitable for experiments such as the screening of DNA libraries.

PMID- 14648115
TI  - The role of shoot-localized processes in the mechanism of Zn efficiency in common
      bean.
AB  - Zn efficiency (ZE) is the ability of plants to maintain high yield under Zn
      deficiency stress in the soil. Two bean ( Phaseolus vulgaris L.) genotypes that
      differed in ZE, Voyager (Zn-efficient) and Avanti (Zn-inefficient), were used for
      this investigation. Plants were grown under controlled-environment conditions in
      chelate-buffered nutrient solution where Zn(2+) activities were controlled at low
      (0.1 pM) or sufficient (150 pM) levels. To investigate the relative contribution
      of the root versus the shoot to ZE, observations of Zn-deficiency symptoms in
      reciprocal grafts of the two genotypes were made. After growth under low-Zn
      conditions, plants of nongrafted Avanti, self-grafted Avanti and reciprocal
      grafts that had the Avanti shoot scion exhibited Zn-deficiency symptoms. However
      nongrafted and self-grafted Voyager, as well as reciprocal grafts with the
      Voyager shoot scion, were healthy with no visible Zn-deficiency symptoms under
      the same growth conditions. More detailed investigations into putative shoot
      localized ZE mechanisms involved determinations of leaf biomass production and Zn
      accumulation, measurements of subcellular Zn compartmentation, activities of two
      Zn-requiring enzymes, carbonic anhydrase and Cu/Zn-dependent superoxide dismutase
      (Co/ZnSOD), as well as the non-Zn-requiring enzyme nitrate reductase. There were
      no differences in shoot tissue Zn concentrations between the Zn-inefficient and
      Zn-efficient genotypes grown under the low-Zn conditions where differences in ZE
      were exhibited. Shoot Zn compartmentation was investigated using radiotracer
      ((65)Zn) efflux analysis and suggested that the Zn-efficient genotype maintains
      higher cytoplasmic Zn concentrations and less Zn in the leaf-cell vacuole,
      compared to leaves from the Zn-inefficient genotype under Zn deficiency. Analysis
      of Zn-requiring enzymes in bean leaves revealed that the Zn-efficient genotype
      maintains significantly higher levels of carbonic anhydrase and Cu/ZnSOD activity
      under Zn deficiency. While these data are not sufficient to allow us to determine
      the specific mechanisms underlying ZE, they certainly point to the shoot as a key
      site where ZE mechanisms are functioning, and could involve processes associated
      with Zn compartmentation and biochemical Zn utilization.

PMID- 14648116
TI  - Acclimation of Arabidopsis thaliana to the light environment: the relationship
      between photosynthetic function and chloroplast composition.
AB  - Plants respond to growth under different environmental conditions by adjusting
      the composition of the photosynthetic apparatus. To investigate the consequences
      of the acclimation strategies adopted by Arabidopsis thaliana, we have assessed
      the functioning of the photosynthetic apparatus in plants with very different
      chloroplast compositions. Using chlorophyll fluorescence analysis, we have
      determined the efficiency of, and capacity for, electron transport, assessed the
      ability to undergo state transitions, and measured non-photochemical quenching
      over a range of actinic irradiances followed by its resolution into fast- and
      slow-relaxing components; parallel measurements of leaf carotenoid composition
      were also carried out. The data clearly show that acclimation serves to maintain
      the electron transport chain in an oxidised state, ensuring efficient
      photochemistry. Furthermore, plants grown in high light have a greater capacity
      for energy-dependent feedback de-excitation, but this is not correlated with
      xanthophyll cycle pigment levels or de-epoxidation state. Surprisingly, even
      plants with very low levels of light-harvesting complexes were able to undergo
      state transitions. We also show that apparent discrepancies between chloroplast
      composition and photosynthetic function can be attributed to varying degrees of
      light penetration through the leaf. Thus, leaf chlorophyll content is an
      important factor influencing acclimation within the leaf.

PMID- 14648117
TI  - Cotton fiber germin-like protein. I. Molecular cloning and gene expression.
AB  - The presence of cotton ( Gossypium hirsutum L.) fiber transcripts coding for a
      germin-like protein (GLP) was revealed by differential display analysis in which
      early stages of cotton fiber development between a wild type line, Texas Marker-1
      (TM1) and a near isogenic mutant, Naked Seed (N1) were compared. Transcripts of
      the cotton GLP ( GhGLP1) accumulated specifically in TM1, but did not accumulate
      in the mutant although the GhGLP1 gene was present in both lines. The deduced
      protein sequence of GhGLP1 is similar to Prunus persica auxin-binding proteins, a
      barley ADP-glucose pyrophosphatase/phosphodiesterase and two different classes of
      hydrogen peroxide-producing enzymes: wheat germin oxalate oxidase and moss
      extracellular Mn-superoxide dismutase. Cotton GLPs constitute a multigene family
      like those of Arabidopsis, rice, soybean, and barley. GhGLP1 transcripts
      accumulated to their highest levels during the period of fiber expansion,
      followed by a sharp decline when the rate of cell expansion decreased. While
      germins and GLPs appear to be involved in defense mechanisms in some plants, both
      biotic and abiotic stress down-regulated the expression of GhGLP1. Numerous
      functions have been proposed for dicot GLPs. However, to date, there is little
      direct evidence for how these proteins function in vivo. The association of
      maximal GhGLP1 expression with stages of maximal cotton fiber elongation suggests
      that some GLPs may be important for cell wall expansion.

PMID- 14648118
TI  - Heterologous expression of a ketohexokinase in potato plants leads to inhibited
      rates of photosynthesis, severe growth retardation and abnormal leaf development.
AB  - In the present paper we investigated the effect of heterologous expression of a
      rat liver ketohexokinase in potato (Solanum tuberosum L.) plants with the aim of
      investigating the role of fructose 1-phosphate in plant metabolism. Plants were
      generated that contained appreciable activity of ketohexokinase but did not
      accumulate fructose 1-phosphate. They were, however, characterised by a severe
      growth retardation and abnormal leaf development. Studies of (14)CO(2)
      assimilation and metabolism, and of the levels of photosynthetic pigments,
      revealed that these lines exhibited restricted photosynthesis. Despite this fact,
      the levels of starch and soluble sugars remained relatively constant. Analysis of
      intermediates of starch and sucrose biosynthesis revealed large increases in the
      triose phosphate and fructose 1,6-bisphosphate pools but relatively unaltered
      levels of inorganic phosphate and 3-phosphoglycerate, and these lines were also
      characterised by an accumulation of glyceraldehyde. The transformants neither
      displayed consistent changes in the activities of Calvin cycle enzymes nor in
      enzymes of sucrose synthesis but displayed a metabolic profile partially
      reminiscent of that brought about by end-product limitation, but most likely
      caused by an inhibition of photosynthesis brought about by the accumulation of
      glyceraldehyde. Analysis of the metabolite contents in lamina and vein fractions
      of the leaf, and of the enzymes of carbohydrate oxidation indicate that the
      phloem-enriched veins of ketohexokinase-expressing leaves tend toward hypoxia and
      indicate a problem of phloem transport.

PMID- 14648119
TI  - Glucose delays seed germination in Arabidopsis thaliana.
AB  - Here we report that glucose delays germination of Arabidopsis thaliana (L.)
      Heynh. seeds at concentrations below those known to inhibit early seedling
      development. This inhibition acts on embryo growth and is independent of
      hexokinase (HXK) function. Hormones and hormone inhibitors were applied to the
      germination media and several hormone biosynthesis and signalling mutants were
      tested on glucose media to investigate a possible role of abscisic acid (ABA),
      gibberellin and ethylene in the glucose-induced germination delay. Results
      indicate that the germination inhibition by glucose cannot be antagonized by
      ethylene or gibberellin and is independent of the HXK1/ABA/ ABI4 signalling
      cascade. These findings suggest that there is a separate regulatory pathway
      independent of ABI2/ ABI4/ ABI5. Thus, in a relatively short time frame sugars
      utilize different signalling cascades to inhibit germination and post-germination
      growth, underlining the complexity of sugar responses.

PMID- 14648120
TI  - Kinetic properties of a micronutrient transporter from Pisum sativum indicate a
      primary function in Fe uptake from the soil.
AB  - Fe uptake in dicotyledonous plants is mediated by a root plasma membrane-bound
      ferric reductase that reduces extracellular Fe(III)-chelates, releasing Fe(2+)
      ions, which are then absorbed via a metal ion transporter. We previously showed
      that Fe deficiency induces an increased capacity to absorb Fe and other
      micronutrient and heavy metals such as Zn(2+) and Cd(2+) into pea ( Pisum sativum
      L.) roots [Cohen et al. (1998) Plant Physiol 116:1063-1072). To investigate the
      molecular basis for this phenomenon, an Fe-regulated transporter that is a
      homologue of the Arabidopsis IRT1 micronutrient transporter was isolated from pea
      seedlings. This cDNA clone, designated RIT1 for root iron transporter, encodes a
      348 amino acid polypeptide with eight putative membrane-spanning domains that is
      induced under Fe deficiency and can functionally complement yeast mutants
      defective in high- and low-affinity Fe transport. Chelate buffer techniques were
      used to control Fe(2+) in the uptake solution at nanomolar activities
      representative of those found in the rhizosphere, and radiotracer methodologies
      were employed to show that RIT1 is a very high-affinity (59)Fe(2+) uptake system
      ( K(m) =54-93 nM). Additionally, radiotracer ((65)Zn, (109)Cd) flux techniques
      were used to show that RIT can also mediate a lower affinity Zn and Cd influx (
      K(m) of 4 and 100 microM, for Zn(2+) and Cd(2+), respectively). These findings
      suggest that, in typical agricultural soils, RIT1 functions primarily as a high
      affinity Fe(2+) transporter that mediates root Fe acquisition. This is consistent
      with recent findings with Arabidopsis IRT1 knockout mutants that strongly suggest
      that this transporter plays a key role in root Fe uptake and nutrition. However,
      the ability of RIT1 to facilitate Zn and Cd uptake when these metals are present
      at elevated concentrations suggests that RIT1 may be one pathway for the entry of
      toxic metals into the food chain. Furthermore, the finding that plant Fe
      deficiency status may promote heavy metal uptake via increased expression of this
      transporter could have implications both for human nutrition and also for
      phytoremediation, the use of terrestrial plants to sequester toxic metals from
      contaminated soil.

PMID- 14648121
TI  - Functional expression in yeast of an N-deleted form of At-ACA8, a plasma membrane
      Ca(2+)-ATPase of Arabidopsis thaliana, and characterization of a hyperactive
      mutant.
AB  - A constitutively active form of At-ACA8, a plasma membrane Ca(2+)-ATPase from
      Arabidopsis thaliana (L.) Heynh., from which the first 74 amino acids containing
      the calmodulin-binding domain (delta74- At-ACA8) had been deleted, was expressed
      in Saccharomyces cerevisiae strain K616, which lacks the main endogenous active
      Ca(2+) transport systems. Delta74- At-ACA8 complemented the K616 phenotype,
      making it able to grow in a calcium-depleted medium. Delta74- At-ACA8 protein,
      which co-migrated with the endoplasmic reticulum marker BiP in a sucrose-density
      gradient, catalyzed MgATP-dependent Ca(2+) uptake and Ca(2+)-dependent MgATP
      hydrolysis, and retained the biochemical characteristics of the native plant
      plasma membrane Ca(2+)-ATPase (low specificity for nucleoside triphosphate, high
      sensitivity to inhibition by the fluorescein derivatives erythrosin B and eosin
      Y), thus confirming that it is correctly folded and functional. Substitution of
      the (794)HE residues (numbers refer to full-length At-ACA8) following the highly
      conserved TGDG(TV)NDP(AS)L motif in the cytoplasmic headpiece with two lysine
      residues generated an hyperactive protein, with a catalytic activity 2-fold
      higher than that of delta74- At-ACA8. The (794)HE-->KK mutant was also about 6
      fold more sensitive than delta74- At-ACA8 to inhibition by vanadate, indicating
      that the mutation determines an increase in the proportion of enzyme in the E(2)
      state during the catalytic cycle.

PMID- 14648122
TI  - In skeletal muscle the relaxation of the resting membrane potential induced by
      K(+) permeability changes depends on Cl(-) transport.
AB  - In resting skeletal muscle the potassium permeability is determined by the
      permeability of the inwardly potassium rectifier. Continuous resting membrane
      potential measurements are done to follow the relaxation of the membrane
      potential upon changes in potassium permeability. Inhibition of the inwardly
      potassium rectifier, by extracellular application of 80 microM Ba(2+), causes the
      cell to depolarize with mean time constants as follows: in control 127+/-7 s (
      n=23), in the presence of bumetanide, as an inhibitor of the Na(+)/K(+)/2Cl(-)
      cotransporter, 182+/-23 s ( n=7), in hypertonic media (340 mosmol/kg) 90.4+/-5 s
      ( n=7) and in reduced chloride medium 64+/-8 s ( n=5). The depolarizing
      relaxation of the membrane potential induced by reduction of extracellular
      potassium produces similar results. These time constants are at least three
      orders of magnitude slower than the time constants reported in the literature for
      the inhibition of the inwardly potassium rectifier. Chloride transport affects
      the relaxation of the membrane potential. A further characterization of chloride
      transport is done by following the relaxation of the membrane potential upon
      application of chloride transport modulators. It is argued that the
      electroneutral cotransporter, for which a flux was preliminarily estimated of
      13.4 pmol cm(-2) s(-1), has a considerable role in the processes related to the
      resting membrane potential.

PMID- 14648123
TI  - Characteristics and a functional implication of Ca(2+)-activated K(+) current in
      mouse aortic endothelial cells.
AB  - We employed the patch-clamp technique to investigate a Ca(2+)-activated K(+)
      (K(Ca)) current in cultured mouse aortic endothelial cells (MAECs). In the whole
      cell mode, an increase in cytosolic [Ca(2+)] ([Ca(2+)](i)) to 2 micro M activated
      an outwards current. The [K(+)](o)-dependent change of the reversal potentials
      agreed well with the predicted Nernstian relation, suggesting that it was a K(Ca)
      current. The Hill coefficient (4) and EC(50) (740 nM) were obtained from the
      current/[Ca(2+)](i) relationship. Iberiotoxin (50 nM) or apamin (200 nM) failed
      to inhibit the current, whereas TEA (10 mM) suppressed the current to 73.6+/-1.6%
      of control ( n=9). The intermediate-conductance, Ca(2+)-activated K(+) (IK(Ca))
      channel blockers charybdotoxin (50 nM), clotrimazole (10 micro M) and econazole
      (10 micro M) inhibited the K(Ca) current to 10.5+/-1.3% ( n=6), 16.6+/-3.1% (
      n=6), and 19.3+/-2.5% ( n=5) of control, respectively. The IK(Ca) channel openers
      chlorzoxazone, zoxazolamine and 1-ethyl-2-benz-imidazolinone and the Ca(2+)
      activated Cl(-) channel blocker niflumic acid activated the K(Ca) current. In
      inside-out patches, the single-channel conductance was 17.7 pS in symmetrical
      K(+) solutions. RT-PCR analysis showed transcripts of the murine IK1 channel
      (mIK1) in MAECs. The IK(Ca) channel blockers inhibited the ATP-induced
      [Ca(2+)](i) increase in MAECs and the endothelium-dependent relaxation of mouse
      aortic rings. In addition, the IK(Ca) channel openers augmented ATP-induced
      [Ca(2+)](i) increase in MAECs and evoked endothelium-dependent relaxation of
      mouse aorta. These results suggest that an mIK1-like channel mediates the native
      IK(Ca) current in MAECs and may contribute to endothelium-dependent relaxation by
      modulating MAEC [Ca(2+)](i).

PMID- 14648124
TI  - Activation of agonist and antagonist muscles at different joint angles during
      maximal isometric efforts.
AB  - The purpose of this study was to investigate the influence of different angles of
      the knee joint on the activation level of an agonist (quadriceps femoris muscle)
      and antagonist (biceps femoris muscle) from electromyographic activities and
      activation levels (twitch interpolation). Isometric torque measurements were
      performed on 23 healthy subjects at 10 degrees intervals between 40 degrees and
      110 degrees of knee joint flexion. Superimposed twitches at maximal voluntary
      contraction were applied and the voluntary activation estimated. To quantify the
      antagonist muscle activity, we normalized its integrated EMG (iEMG) value at each
      joint angle with respect to its iEMG value at the same angle when acting as an
      agonist at maximal effort. The activation levels at the knee-flexed position (80
      110 degrees ) were higher than that at the knee-extended position (40-70 degrees
      ). The co-activation levels at 90, 100, and 110 degrees were significantly higher
      than that the other knee angle. These results suggest that the activation level
      of an agonist (quadriceps femoris) muscle and the co-activation level of an
      antagonist (biceps femoris) muscle were higher in longer muscles than in shorter
      muscles. It was also concluded that the risk of knee injuries could be reduced by
      applying these mutual relationships between activation levels of agonist and
      antagonist muscles.

PMID- 14648125
TI  - Eccentric endurance training in subjects with coronary artery disease: a novel
      exercise paradigm in cardiac rehabilitation?
AB  - This study evaluated the effects of 8 weeks of eccentric endurance training (EET)
      in male subjects (age range 42-66 years) with coronary artery disease (CAD). EET
      was compared to concentric endurance training (CET) carried out at the same
      metabolic exercise intensity, three times per week for half an hour. CET ( n=6)
      was done on a conventional cycle ergometer and EET ( n=6) on a custom-built motor
      driven ergometer. During the first 5 weeks of the training program the metabolic
      load was progressively increased to 60% of peak oxygen uptake in both groups. At
      this metabolic load, mechanical work rate achieved was 97 (8) W [mean (SE)] for
      CET and 338 (34) W for EET, respectively. Leg muscle mass was determined by dual
      energy X-ray absorptiometry, quadriceps strength with an isokinetic dynamometer
      and muscle fibre composition of the vastus lateralis muscle with morphometry. The
      leg muscle mass increased significantly in both groups by some 3%. Strength
      parameters of knee extensors improved in EET only. Significant changes of +11
      (4.9)%, +15 (3.2)% and +9 (2.5)% were reached for peak isometric torque and peak
      concentric torques at 60 degrees s(-1) and 120 degrees s(-1), respectively. Fibre
      size increased significantly by 19% in CET only. In conclusion, the present
      investigation showed that EET is feasible in middle-aged CAD patients and has
      functional advantages over CET by increasing muscle strength. Muscle mass
      increased similarly in both groups whereas muscle structural composition was
      differently affected by the respective training protocols. Potential limitations
      of this study are the cautiously chosen conditioning protocol and the restricted
      number of subjects.

PMID- 14648126
TI  - Effects of priming exercise intensity on the dynamic linearity of the pulmonary
      VO(2) response during heavy exercise.
AB  - Prior heavy-intensity exercise facilitates the pulmonary oxygen uptake ( VO(2))
      response during subsequent exercise, such that its kinetics returns towards first
      order. To better understand this "priming" phenomenon, we investigated the effect
      of priming exercise, over a range of intensities, on the VO(2) response to heavy
      intensity cycle ergometry at a work rate of Delta50% [halfway between lactate
      threshold (LT) and VO(2max)]. Eight subjects performed two consecutive 6-min
      bouts separated by 6 min at 20 W. The first bout was each of: no warm-up control
      (CON), sub-lactate threshold (LT) at 80% of LT, and three supra-LT conditions
      (Delta20%, Delta40%, and Delta60%). The VO(2) response during the subsequent bout
      was evaluated using the "effective" time constant (tau'), and the VO(2)
      difference between minutes 3 and 6 (Delta VO(2(6-3))). The goodness-of-fit,
      indicative of "first-order" kinetics, was determined by the residual profile, and
      the mean square of errors (MSEr). The heart rate and blood lactate concentration
      ([La]r) just prior to the second bout were also measured. Compared with CON, tau'
      and Delta VO(2(6-3)) were significantly reduced following all supra-LT priming
      bouts, while the goodness-of-fit was significantly improved following Delta40%
      exercise. Delta VO(2(6-3)) and [La]r were negatively correlated ( P<0.05), unlike
      HR. In conclusion, prior exercise just above, but not below, LT facilitated the
      VO(2) response in a threshold-like manner. Supra-LT priming exercise influenced
      the VO(2) response allowing it to return to within as little as 12% from first
      order (compared to approximately 50% in CON). The associated increases in
      circulating lactate and/or related factors seem to be centrally involved in this
      phenomenon.

PMID- 14648127
TI  - The effect of passive heating and face cooling on perceived exertion during
      exercise in the heat.
AB  - Increased body temperature is thought to be an important component of the higher
      perception of exertion that is a feature of fatigue during exercise in the heat
      but a causal relationship has yet to be demonstrated. We have investigated the
      effect of passive heating on the perception of exertion during a standard bout of
      exercise and also assessed the effect of cooling the head on compensating for the
      increased body temperature on the feelings of exertion. Ten male subjects
      performed a 14-min cycling exercise [average power approximately 63% of maximum
      power output ( W(max))] at an ambient temperature of 35 degrees C at resting
      rectal temperature [mean (SD): 37.49 (0.27) degrees C; control (CON) trial] on
      one occasion, and after sitting in a sauna to raise rectal temperature [mean
      (SD): 38.95(0.13) degrees C; sauna (SAU) trial]. During the exercise, subjects
      reported their ratings of overall perceived exertion (RPE), perceived exertion of
      the legs (RPE(legs)) and thermal comfort (TC). A blood sample was collected by
      the end of the exercise for determination of plasma glucose, lactate and
      prolactin and haematocrit. RPE values were significantly elevated after passive
      heating [mean (SE): 14.5 (0.7) units in CON and 17.2 (0.5) units in SAU, at the
      end of exercise; P<0.001] as were the RPE(legs) ( P<0.01), while ratings of TC
      were similar in CON and SAU trials. Passive heating increased blood glucose (
      P<0.05) but had no effect on lactate at the end of the exercise. Plasma prolactin
      was markedly elevated as a result of the sauna exposure [mean (SE): 1598 (152)
      versus 225 (31) mU l(-1) in SAU and CON trials, respectively; P<0.001]. Six of
      the subjects repeated the two trials but with the face cooled during exercise
      (trials CON(FAN) and SAU(FAN)) that was achieved by combining face fanning and
      spraying the face with a mist of cooled water. Face cooling decreased RPE values
      after sauna to a point that no differences between the two conditions existed.
      RPE(legs) scores and heart rate, however, remained higher in SAU(FAN) compared
      with CON(FAN) ( P<0.05). We conclude that hyperthermia is a causative element of
      the increased perception of exertion during submaximal exercise in the heat and
      that the effect of increased core temperature on the feelings of exertion is
      modulated by face cooling.

PMID- 14648128
TI  - Maturity-associated variation in the growth and functional capacities of youth
      football (soccer) players 13-15 years.
AB  - The objective was to estimate the contribution of experience, body size and
      maturity status to variation in the functional capacities of adolescent football
      (soccer) players. The sample included 69 players 13.2-15.1 years of age from
      three clubs which competed in the highest division for their age group in the
      first Portuguese national division. Height and weight were measured and stage of
      pubic hair development was assessed at clinical examination. The number of years
      of experience in football was obtained at interview. Three tests of functional
      capacity were administered: 30-m dash (running speed), vertical jump (explosive
      power) and a yo-yo intermittent endurance test (aerobic resistance). Multiple
      linear regression analysis was used to estimate the relative contributions of
      age, stage of sexual maturity, height, weight and years of formal training in
      football to the three indicators of functional capacity. Stage of puberty, body
      size and years of training accounted for 21% to 50% of the variance in the three
      tasks. Sexual maturity status was the primary contributor to the variance in the
      intermittent shuttle run, whereas weight and height were the primary contributors
      to the explained variance in the 30-m dash and vertical jump, respectively. In
      conclusion, biological maturity status significantly influences the functional
      capacity of adolescent football players 13-15 years of age. Training is a
      significant contributor to aerobic resistance, whereas weight and height are
      significant contributors to the sprint and vertical jump, respectively.

PMID- 14648129
TI  - Torque loss induced by repetitive maximal eccentric contractions is marginally
      influenced by work-to-rest ratio.
AB  - The influence of different work-to-rest (W:R) ratios during fatigue induced by
      maximal eccentric contractions is unknown. The present study sought to expand the
      understanding of the task-dependent nature of eccentric contractions, and the
      associated fatigue, during exercise and acute as well as extended recovery
      periods. Using a Biodex multi-joint dynamometer, the ankle dorsiflexors of eight
      men [26 (4) years] were fatigued with 150 maximal eccentric contractions. Set
      structure was manipulated such that one leg performed 3 sets of 50 repetitions
      (short rest protocol, SRP), and the other leg performed 15 sets of 10 repetitions
      (long rest protocol, LRP). A 1-min rest interval separated each set, which
      resulted in 2 and 14 min of total rest for the SRP and the LRP, respectively. At
      fatigue, the SRP demonstrated a marginally greater loss of average peak eccentric
      torque than the LRP ( P<0.05). In the acute period following fatigue, isometric
      peak torque loss and the degree of low-frequency fatigue (LFF) were not recovered
      ( P<0.05) and were equivalent for both protocols. Significant impairment of both
      eccentric and isometric torque was persistent and equal for each protocol at 96 h
      of recovery ( P<0.05). These findings suggest that the W:R ratio has a modest
      influence on the fatigue (torque loss) induced by maximal eccentric contractions,
      but maximal isometric torque during recovery and LFF are insensitive to changes
      in total rest time.

PMID- 14648130
TI  - Respiratory symptoms and ex vivo cytokine release are associated in workers
      processing herring.
AB  - OBJECTIVE: To determine the prevalence of respiratory symptoms among workers
      processing herring and assess ex vivo cytokine release in response to agents at
      their workplace. METHODS: We applied a questionnaire, and performed skin prick
      testing and pulmonary investigations in 36 workers at two herring factories,
      using 31 municipal workers as controls. In a whole blood assay (WBA), venous
      blood from the subjects was incubated with lipopolysaccharide (LPS), beta(1,3)
      glucan or sterile-filtered, fish constituents such as skin and rinsing water. We
      determined the IL-1beta and IL-8 release in the plasma by chemiluminescence
      ELISA. RESULTS: Among smoking fish-factory workers the forced vital capacity
      (FVC) was higher (per cent predicted 92.0 vs 85.0; P=0.028) than among municipal
      workers. Fish rinsing water induced WBA IL-8 release to higher levels than LPS
      and glucan. Among non-smokers the induced IL-1beta release for rinsing water (
      P=0.007) and the IL-8 release for skin ( P=0.001) and meat ( P=0.003) were higher
      in fish-factory workers than in municipal workers. The IL-1beta release for
      rinsing water ( P=0.028) and skin ( P=0.041) was higher among non-smokers than
      among smokers, and so was the IL-8 release for rinsing water ( P=0.008).
      CONCLUSIONS: Assessing the cytokine release by use of the WBA we identified
      substances in the occupational environment with a pro-inflammatory potential
      comparable to that of LPS. The cytokine release for fish constituents was highest
      among non-smoking fish-factory workers. The results suggest a priming effect of
      the work exposure.

PMID- 14648131
TI  - Exposure to volatile organic compounds in residences adjacent to dyeing
      industrial complex.
AB  - OBJECTIVES: The present study was designed to evaluate residential exposure to
      selected volatile organic compounds (VOCs) relative to the proximity of the Daegu
      dyeing industrial complex (DDIC). METHODS: A series of surveys was conducted to
      measure the concentrations of five aromatic VOCs (toluene, benzene, m-xylene, p
      xylene, and o-xylene) and methyl tertiary-butyl ether (MTBE) in the industrial
      outdoor air within the DDIC and in residential outdoor and indoor air based on
      the relative proximity of the DDIC. RESULTS: The geometric mean (GM) toluene
      value for the outdoor air samples from residential area R1 located near the DDIC
      (255 microg/m(3)) was about seven-times higher than that from residential area R2
      located further away from the DDIC (36.9 microg/m(3)), whereas no significant
      difference was found in the outdoor air concentrations of the other target
      compounds between the two residential areas. Moreover, the elevated outdoor
      toluene levels outweighed the indoor sources with respect to the environmental
      exposure of residents near the DDIC. However, for the other target VOCs there was
      no significant difference between the residential exposure of residents living
      close to and a certain distance away from the DDIC. CONCLUSIONS: The present
      study confirmed that residents in neighborhoods near the DDIC were exposed to
      elevated outdoor toluene levels compared with residents living further away from
      such a source. Furthermore, it appeared that the DDIC was a potential contributor
      to the nearby residential outdoor toluene levels.

PMID- 14648133
TI  - Connective tissue growth factor in tear film of the horse: detection,
      identification and origin.
AB  - BACKGROUND: Healing of corneal ulcers in horses is often associated with profound
      corneal stromal fibrosis and scar formation resulting in visual impairment.
      Connective tissue growth factor (CTGF) is a fibrogenic cytokine involved in wound
      healing and scarring. The purpose of this study was to determine whether CTGF was
      present in the tear fluid of normal horse eyes and the eyes of horses with
      corneal ulcers in order to evaluate the role of CTGF in corneal wound healing and
      corneal scar formation. METHODS: Tear fluid samples were collected from 65 eyes
      of 44 horses; 32 samples from normal eyes, 21 samples from eyes with corneal
      ulceration, and 12 samples from the unaffected contralateral eyes of horses with
      ulcers. CTGF levels in the tears were determined by enzyme immunoassay using goat
      IgG against human CTGF. Antigenetic similarity of human and horse CTGF was
      established in a bio-equivalence assay. The identity of horse CTGF was confirmed
      by western blot. Lacrimal and nictitating membrane glands were investigated by
      immunohistochemistry in the attempt to clarify the origin of tear fluid CTGF.
      RESULTS: CTGF was detected in tear film of 23 normal unaffected eyes (72%) and 8
      normal contralateral eyes (67%), with the mean CTGF levels (+/- SEM) being 51.5+/
      19.2 and 13.4+/-3.9 ng/ml respectively. CTGF was found in 8 eyes with corneal
      ulcers (38%) with the mean CTGF concentration of 26.3+/-14.8 ng/ml. Western blot
      identified the protein detected as CTGF. The identification of CTGF in lacrimal
      glands suggests a major role of these glands in the presence of CTGF in tears.
      CONCLUSIONS: CTGF is present in horse tear fluid and derives, at least partly,
      from the lacrimal gland. Equine CTGF has strong antigenic similarity with human
      CTGF. Corneal disease leads to a decrease of CTGF concentrations in tears. The
      possible role of CTGF in the healing process of ocular surface requires further
      investigation.

PMID- 14648134
TI  - Factors associated with the development of chorioretinal atrophy around choroidal
      neovascularization in pathologic myopia.
AB  - PURPOSE: To examine the influencing factors on the development of chorioretinal
      atrophy, which is the main cause of long-term visual decrease in myopic choroidal
      neovascularization (CNV), in a large series of highly myopic patients. METHODS:
      Sixty-five patients (81 eyes) with myopic CNV were studied retrospectively. The
      influence of the patient's age, refractive error, axial length, visual acuity at
      onset of CNV, size of CNV, and grade of myopic retinopathy on the extent of
      chorioretinal atrophy more than 3 years after CNV onset was investigated by means
      of multiple linear regression analysis. RESULTS: Seventy-seven of 81 eyes (95.1%)
      developed chorioretinal atrophy around myopic CNV during the follow-up period.
      Multiple linear regression revealed that age was the most influencing factor for
      the development of chorioretinal atrophy in all the subjects. When we divided the
      subjects into two groups according to their age, however, CNV size was the only
      factor to influence the development of chorioretinal atrophy in the patients
      younger than 40 years, whereas age was still the only influencing factor in those
      older than 40 years. CONCLUSIONS: The factors influencing the development of
      chorioretinal atrophy differ according to patient age. Local factors, such as CNV
      size, determine the tendency to develop chorioretinal atrophy in young patients.
      Systemic factors, such as patient age, play a greater part in older subjects.

PMID- 14648135
TI  - Epimacular proliferative response following internal limiting membrane peeling
      for idiopathic macular holes.
AB  - PURPOSE: To present two patients who underwent surgery for an idiopathic macular
      hole (IMH) with internal limiting membrane (ILM) peeling and developed an
      epimacular proliferative response. METHODS: Observational case report. Two
      patients with an IMH underwent pars plana vitrectomy with ILM peeling. Ophthalmic
      examination including optical coherence tomography (OCT) was performed pre- and
      postoperatively. In both cases, scanning laser ophthalmoscopy (SLO) was performed
      postoperatively. RESULTS: In the first case, the closure of the macular hole (MH)
      was confirmed ophthalmoscopically and by OCT following the surgery. At 2 months
      postoperatively, a thin epiretinal membrane (ERM) developed over the nasal macula
      area where the ILM had been peeled. The patient's visual acuity had recovered to
      1.0 but she complained of metamorphopsia. At 18 months postoperatively, the thin
      ERM around the nasal fovea remained and her visual acuity was still 1.0. In the
      second case, the MH was sealed after the surgery, and the patient's visual acuity
      had improved to 1.0 at 3 months, but an indistinct ERM developed in the macular
      region where the ILM had been peeled. Two years after the operation, her VA was
      still 1.0. One and two years postoperatively, a thin epimacular proliferation
      remained unchanged; in addition, the OCT and SLO images remained stable.
      CONCLUSION: Two patients who underwent IMH surgery with ILM peeling developed an
      epimacular proliferative response postoperatively. We suggest that the injury
      associated with the ILM peeling may have stimulated glial proliferation.

PMID- 14648132
TI  - Innovative techniques and applications in histochemistry and cell biology.
AB  - Recent studies documenting novel histochemical methods and applications in cell
      biology and in other areas of the life sciences have again rendered insights into
      structure and functions of tissues, cells, and cellular components to the level
      of proteins and genes. Particularly, sophisticated microscopic techniques have
      proved to be able to significantly advance our knowledge. Findings of recent
      investigations representing this progress are summarized in the present review.

PMID- 14648136
TI  - Painful isolated Horner's syndrome caused by pontine ischaemia.
AB  - PURPOSE: To alert ophthalmologists to the possibility of brainstem ischaemia in
      patients with isolated Horner's syndrome. DESIGN: Observational case report.
      METHODS: Neuro-ophthalmological and neuroimaging assessment of a 59-year-old
      woman presenting with an isolated Horner's syndrome after an episode of headache.
      RESULTS: Horner's syndrome was pharmacologically localised to a first- or second
      order sympathetic neuron on the right. Magnetic resonance imaging (MRI) showed a
      small ischaemic lesion at the transition between pons and midbrain, lateral to
      the anterolateral system involving the sympathetic tract on the right side.
      CONCLUSION: An isolated Horner's syndrome may be the presenting sign of a
      brainstem infarction. This case report stresses the importance of a rational
      approach to Horner's syndrome and the need to order accurate MRI.

PMID- 14648137
TI  - Autoregulative behavior of retinal arteries and veins during changes of perfusion
      pressure: a clinical study.
AB  - PURPOSE: To investigate the autoregulative response of large retinal vessels to
      artificial reduction of perfusion pressure. METHODS: The diameters of a venous
      and an arterial segment (each approx.1.5 mm in length) in one eye of each of 13
      healthy volunteers (age 54.5+/-18 years) were measured continuously using the
      Retinal Vessel Analyzer (Imedos, Weimar, Germany). The intraocular pressure (IOP;
      mean before examination 13.7+/-2.9 mmHg) was increased by 21.2+/-3.5 mmHg by
      means of a suction cup in order to produce a temporary reduction of the retinal
      perfusion pressure. The RVA measurements were taken for 2 min without artificial
      intervention (baseline), for 100 s during IOP elevation, and for up to 10 min
      after removal of the suction cup. RESULTS: A significant response of arterial and
      venous diameters to the provocation was found ( P<0.02, ANOVA). The arterial and
      venous responses were opposite: Whereas the artificially elevated IOP increased
      the arterial diameter by +1.9+/-4.5%, the venous vessel diameter decreased by 
      2.6+/-3.5% ( P<0.02, Mann-Whitney U-test). After normalization of the IOP the
      arterial diameter fell slightly below the baseline value, while the veins
      underwent temporary dilation by +5.9+/-3.3% ( P<0.001). The mean systemic blood
      pressure did not change significantly during the investigation. CONCLUSION:
      Retinal arteries and veins of healthy volunteers exhibited opposite
      autoregulative behavior in response to perfusion pressure changes. This is
      believed to be due to the different regulative functions of arteries and veins.

PMID- 14648138
TI  - Laser interference biometry versus ultrasound biometry in certain clinical
      conditions.
AB  - PURPOSE: To compare laser interference biometry (LIB) with conventional
      ultrasound biometry in certain clinical conditions such as globe deformities,
      eccentric fixation, retinal detachment, macular edema or silicone oil-filled
      eyes. SETTING: Department of Ophthalmology, Wurzburg University Eye Hospital,
      Germany. METHODS: We evaluated all patients who came to our university hospital
      for axial length measurement with our routine immersion biometry system
      (Grieshaber Biometry System) and compared the results with those obtained using
      the Zeiss IOLMaster of Carl Zeiss Jena, the commercially available LIB device.
      RESULTS: Selected case reports demonstrate the advantages and disadvantages of
      LIB. Advantages of LIB were found in patients with asymmetrically shaped globes,
      eccentric fixation, silicone oil-filled eyes and a fearful/nervous disposition.
      Disadvantages of the system were revealed in cases of retinal detachment, severe
      opacities along the visual axis and poor patient cooperation. CONCLUSION: We
      showed that LIB is a valuable addition to the choice of biometric devices, when
      used with medical understanding.

PMID- 14648140
TI  - Intensified postoperative care versus conventional follow-up: a retrospective
      long-term analysis of 177 trabeculectomies.
AB  - PURPOSE: To evaluate the long-term outcome of trabeculectomy under the conditions
      of intensified postoperative care (IPC) compared with conventional follow-up.
      METHODS: One hundred and seventy-seven consecutive primary trabeculectomies (168
      patients) with a median follow-up of 4.5 years were retrospectively analyzed at
      the University Eye Hospital, Wurzburg. Seventy-three trabeculectomies (70
      patients) were followed by the surgeon under the conditions of IPC (group 1), and
      104 trabeculectomies (98 patients) were followed by other ophthalmologists
      without IPC (group 2). The following measures to control wound healing were
      predominantly used in group 1: (1) increase in topical steroid administration if
      corkscrew vessels were present; (2) repeated injections of 5-fluorouracil (5-FU)
      at the beginning of bleb scarring; and/or (3) needling plus 5-FU administration
      if an encapsulated bleb developed. Postoperative intraocular pressure (IOP) was
      defined as "successful" when it did not exceed 21 mmHg and was at least 20% lower
      than the treated preoperative IOP. Stable visual acuity was defined as +/-1 line.
      RESULTS: The success rates of IOP control were about 95% in both groups. In the
      IPC group 45 of 73 eyes fulfilled all success criteria without additional anti
      glaucoma medication (61.6%), whereas in conventional follow-up only 33 of 104
      eyes fulfilled all success criteria without medication (31.7%). CONCLUSIONS: This
      study demonstrates that a much higher proportion of filtering blebs reach target
      IOP without medication if measures of IPC are consistently used by a glaucoma
      specialist when necessary.

PMID- 14648141
TI  - Histopathological study of the anterior lens capsule with a double-ring sign.
AB  - BACKGROUND: A 'double-ring' sign may be seen during continuous curvilinear
      anterior capsulorhexis in cataract surgery. This sign has been attributed to
      partial splitting of the anterior lens capsule at the continuous curvilinear
      anterior capsulorhexis edge. Because horizontal intracapsular splits away from
      the capsule edge have also been reported, a double-ring sign has been
      hypothesized to be a precursor to true exfoliation. We report new
      histopathological findings for both anterior capsule and lens epithelium changes,
      the latter being similar to those of true exfoliation. METHODS: Three anterior
      capsules from two patients with a double-ring sign during capsulorhexis were
      examined via light and transmission electron microscopy. RESULTS: Light
      microscopy revealed step formations in the capsule edges and surface-parallel
      intracapsular splits in the anterior capsules. Transmission electron microscopy
      revealed stratified, banded structures consisting of alternating electron-dense
      and -lucent granular belts (300-400 nm) at the central area of the anterior
      capsule, as well as vacuole-like spaces and expansion of intercellular spaces in
      the lens epithelium. CONCLUSIONS: The thickened, stratified structure of the
      anterior capsule suggests abnormal lens epithelium in patients with a double-ring
      sign. The horizontal splits in the anterior capsule, with concomitant epithelial
      changes, i.e., the vacuole-like spaces and widened intercellular spaces, support
      the relation between a double-ring sign and true exfoliation.

PMID- 14648142
TI  - Headaches with (ipsilateral) autonomic symptoms.
AB  - Primary short-lasting headaches broadly divide themselves into those associated
      with autonomic symptoms, so called trigemino-autonomic cephalgias (TACs), and
      those with little autonomic syndromes. The trigeminoautonomic cephalgias include
      cluster headache and paroxysmal hemicranias, in which head pain and cranial
      autonomic symptoms are prominent. The most striking feature of cluster headache
      is the circadian and circannual periodicity of the attacks. Inheritance may play
      a role in some families. The attacks are of extreme intensity, of short duration,
      occur unilaterally, and are accompanied by symptoms of autonomic dysfunction.
      Medical treatment includes both acute therapy aimed at aborting individual
      attacks and prophylactic therapy aimed at preventing recurrent attacks during the
      cluster period. Some types of trigemino-autonomic headaches, such as paroxysmal
      hemicrania and hemicrania continua have, unlike cluster headaches, a very robust
      response to indomethacin, leading to a consideration of indomethacin-sensitive
      headaches.

PMID- 14648143
TI  - The spectrum of lower motor neuron syndromes.
AB  - This review discusses the most important lower motor neuron syndromes. This
      relatively rare group of syndromes has not been well described clinically. Two
      subgroups can be distinguished: patients in whom motor neurons (lower motor
      neuron disease (LMND)) are primarily affected or motor axons and their
      surrounding myelin (multifocal motor neuropathy (MMN)), both leading to muscle
      atrophy and weakness. Both hereditary and sporadic forms of LMND have been
      described. The discussion of recent advances in the genetic knowledge of several
      hereditary forms of LMND may lead to a better understanding of the
      pathophysiology and the development of therapeutic strategies. By contrast, the
      pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to
      consider the various sporadic forms of LMND, discussed in this review, as
      separate diseases. Because the diagnostic and therapeutic options may differ, it
      would seem rational to consider sporadic LMND as a spectrum of syndromes which
      can be distinguished from each other on the basis of clinical presentation.MMN is
      a lower motor neuron syndrome with presumed immunemediated pathogenesis. Evidence
      of motor conduction block on nerve conduction studies and a positive response to
      treatment with intravenous immunoglobulins (IVIg) are considered the most
      relevant criteria for the diagnosis of MMN. As it is treatable, it is important
      to distinguish MMN from LMND. Careful electrophysiological analysis in the search
      for conduction block is, therefore, required in all adult patients with pure
      lower motor neuron syndromes. For the individual patient, distinction between the
      various lower motor neuron syndromes is important as it enables the physician to
      provide adequate information over the disease course in LMND and to facilitate
      early treatment in MMN.

PMID- 14648144
TI  - High field MRI correlates of myelin content and axonal density in multiple
      sclerosis--a post-mortem study of the spinal cord.
AB  - Different MRI techniques are used to investigate multiple sclerosis (MS) in vivo.
      The pathological specificity of these techniques is poorly understood, in
      particular their relationship to demyelination and axonal loss. The aim of this
      study was to evaluate the pathological substrate of high field MRI in post-mortem
      (PM) spinal cord (SC) of patients with MS. MRI was performed in PMSCs of four MS
      patients and a healthy subject on a 7 Tesla machine. Quantitative MRI maps (PD;
      T2; T1; magnetization transfer ratio, MTR; diffusion weighted imaging) were
      obtained. After scanning, the myelin content and the axonal density of the
      specimens were evaluated neuropathologically using quantitative techniques.
      Myelin content and axonal density correlated strongly with MTR, T1, PD, and
      diffusion anisotropy, but only moderately with T2 and weakly with the apparent
      diffusion coefficient. Quantitative MR measures provide a promising tool to
      evaluate components of MS pathology that are clinically meaningful. Further
      studies are warranted to investigate the potential of new quantitative MR
      measures to enable a distinction between axonal loss and demyelination and
      between demyelinated and remyelinated lesions.

PMID- 14648145
TI  - The diagnostic difficulties of meningeal and intracerebral plasma cell granulomas
      -presentation of three cases.
AB  - Meningeal and intracerebral plasma cell granulomas are uncommon inflammatory
      lesions of unknown etiology. In this paper the diagnostic difficulties in two
      patients with meningeal plasma cell granuloma and one patient with intracerebral
      plasma cell granuloma are described. The first patient had an intracranial extra
      axial lesion, which was first diagnosed as a meningioma. One and a half years
      later she underwent a second resection for recurrent tumor growth and the
      diagnosis of a meningeal plasma cell granuloma was made. The second patient was
      treated for a central nervous system B-cell lymphoma but proved to have an
      intracerebral plasma cell granuloma in retrospect 11 years later. In the third
      patient tuberculous meningitis was considered to be the most likely diagnosis
      because infratentorial contrast-enhanced thickened meninges (pachymeningitis)
      were found together with a high protein level in the cerebrospinal fluid and a
      positive Mantoux test. However, pathological examination of an extra-axial,
      cervical lesion that was operated upon revealed a meningeal plasma cell
      granuloma. These cases show the importance of diagnosing a meningeal or
      intracerebral plasma cell granuloma correctly, since it has both therapeutical
      and prognostic implications.

PMID- 14648146
TI  - Oculopharyngeal muscular dystrophy with limb girdle weakness as major complaint.
AB  - This first description of the oculopharyngeal muscular dystrophy (OPMD) phenotype
      in Dutch patients shows that limb girdle weakness can occur early in the course
      of disease and can give the first and major complaint in OPMD patients. The aim
      of this study was to examine clinically, histologically and genetically all Dutch
      OPMD patients known at the Neuromuscular Centre Nijmegen, to measure the limb
      girdle weakness (MRC scale) and to quantify the consequences of the limb girdle
      weakness on daily activities (Rankin scale). Remarkable in this population was
      the early onset and the severity of the limb girdle weakness. We found a higher
      percentage of patients with limb girdle weakness than reported before in non
      Dutch OPMD populations. This limb girdle weakness caused limitations in daily
      activities more than the other symptoms of OPMD. It was difficult to compare the
      severity of the limb girdle weakness of Dutch patients with other patients
      because of the lack of data related to quantification of limb girdle weakness in
      non-Dutch OPMD patients. Because of the influence of the limb girdle weakness on
      the daily activities of the patients, we recommend that more attention is paid to
      the proximal limb muscles in OPMD patients early in the course of the disease.

PMID- 14648147
TI  - Analysis of HLA class I and II alleles in sporadic inclusion-body myositis.
AB  - Sporadic inclusion body myositis (s-IBM) is characterised by progressive weakness
      of proximal and distal limb muscles. Most patients are aged over 50 years at
      disease onset. Muscle biopsy reveals an inflammatory myopathy and cytoplasmic
      amyloid deposits. The mononuclear infiltrate is dominated by CD8+ T-cells.
      Several investigators have described associations between s-IBM and certain HLA
      antigens and alleles. However, to date neither HLA class I nor II alleles have
      been analysed in a large series of patients. We typed various HLA class I and II
      alleles in 47 patients suffering from s-IBM using sequence specific-primer pairs
      (SSPPCR). The results were compared with published German controls. Additional
      Bonferroni adjustment was performed over all allele groups corresponding to
      serologically defined antigens within one HLA class I or II locus. After
      Bonferroni adjustment, we found a significant increase in frequency of the
      following HLA alleles for s-IBM patients when compared with normal controls: A*03
      (p = 0.0002), B*08 (p = 0.002), DRB1*03 (p = 0.0000002), and DQB1*05 (p = 0.02).
      HLA typing may be helpful to distinguish between subgroups of s-IBM patients.
      Moreover, HLA analysis may aid in identifying patients who might profit from
      future therapeutic strategies.

PMID- 14648148
TI  - Diagnosis of Lyme neuroborreliosis with antibodies to recombinant proteins DbpA,
      BBK32, and OspC, and VlsE IR6 peptide.
AB  - Three recombinant antigens, decorin binding protein A (DbpA), BBK32, and outer
      surface protein C (OspC), and IR(6) peptide of borrelial VlsE protein, were
      evaluated for the diagnosis of neuroborreliosis (NB), using cerebrospinal fluid
      (CSF) and serum samples from 89 patients. Their performances in enzyme-linked
      immunosorbent assay (ELISA) were compared with that of commercial flagella
      antigen. IgG ELISAs were performed with three variants of each recombinant
      antigen originating from Borrelia burgdorferi sensu stricto, B. afzelii and B.
      garinii, and with the IR(6) peptide. IgM antibodies were analysed against OspC
      and flagella. Of the patients whose CSF contained elevated anti-flagella IgG
      antibodies, 93% were positive for at least three of the new antigens. Of those
      with negative or borderline CSF anti-flagella antibodies, 51% were positive for
      three new antigens. Antibodies to BBK32 were detectable mainly in early disease.
      Antibodies to DbpA and IR(6) were observed in early and late NB. The use of the
      new antigens at presentation of the disease improved the laboratory diagnosis of
      NB. In IgG ELISAs, the diagnostic sensitivity of assays with the new antigens was
      between 75 and 88%, but was only 52% with the flagella antigen. The
      discriminatory power between patient and control samples appeared better in the
      CSF than in the serum. We suggest that assessment of CSF antibodies to at least
      two antigens, using either flagella and one of the new antigens or two of the new
      antigens, would improve the current diagnostic yield of NB.

PMID- 14648149
TI  - Muscle structural changes in mitochondrial myopathy relate to genotype.
AB  - It is well known that morphological changes at the cellular level occur in muscle
      of patients with mitochondrial myopathy (MM), but changes in muscle structure
      with fat infiltration and gross variation of muscle fiber size with giant fibers,
      normally encountered in the muscular dystrophies, have typically not been
      associated with mitochondrial disease. We investigated gross and microscopic
      muscle morphology in thigh muscles by muscle biopsy and MRI in 16 patients with
      MM, and compared findings with those obtained in muscular dystrophy patients and
      healthy subjects. Changes of muscle architecture, similar to those found in the
      group of muscular dystrophy patients occurred consistently in patients with a
      high mutation load for single, largescale deletions of mtDNA, but were absent in
      all patients with the 3243A-->G mtDNA point mutation. Dystrophic changes of
      muscle architecture were also present in one MM patient with a unique, sporadic
      mutation in the mtDNA tRNA(Met) gene. These findings provide evidence that
      morphological changes in muscle of MM patients are common and may resemble those
      of muscular dystrophies, but that development of dystrophic-like changes in
      muscle relate to genotype.

PMID- 14648150
TI  - Dopamine transporter binding in chronic manganese intoxication.
AB  - Chronic exposure to manganese may induce parkinsonism similar to idiopathic
      Parkinson's disease (PD). However, clinical manifestations of manganism also have
      some features different from PD. The mechanisms of manganese-induced parkinsonism
      remain not fully understood. (99m)Tc-TRODAT-1 is a cocaine analogue that can bind
      to the dopamine transporter (DAT) site reflecting the function of presynaptic
      dopaminergic terminals. The purpose of this study was to evaluate DAT function
      using (99m)Tc-TRODAT-1 to investigate the integrity of the presynaptic
      dopaminergic terminals in manganese-induced parkinsonism. Brain (99m)Tc-TRODAT-1
      single photon emission computed tomography was performed in 4 patients with
      chronic manganese intoxication in a ferromanganese smelting plant in Taiwan.
      Twelve PD patients and 12 healthy volunteers served as abnormal and normal
      controls, respectively. Clinically, all manganism patients had a bradykinetic
      rigid syndrome. The scores of the Unified Parkinson's Disease Rating Scale ranged
      between 19 and 64. The uptake values of the (99m)Tc-TRODAT-1 were 0.868+/-0.136
      in the right corpus striatum and 0.865+/-0.118 in the left, as compared with
      0.951+/-0.059 and 0.956+/-0.058, respectively for the normal controls. The data
      were significantly higher than 0.250+/-0.070 and 0.317+/-0.066 respectively for
      the PD patients. Interestingly, there was a mild decrease in the uptake of
      (99m)Tc-TRODAT-1 in the putamen and the ratio of putamen and caudate when
      compared with the normal controls. Although the DAT shows a slight decrease in
      the putamen of manganism patients as compared with that of the normal controls,
      the data indicate that the presynaptic dopaminergic terminals are not the main
      target of chronic manganese intoxication. In addition (99m)Tc-TRODAT-1 SPECT can
      provide a useful, convenient and inexpensive tool for differentiation between
      chronic manganism and PD.

PMID- 14648151
TI  - Cognitive impairment in patients with carotid artery occlusion and ipsilateral
      transient ischemic attacks.
AB  - Although transient ischemic attacks (TIAs) by definition do not cause lasting
      neurological deficits, cognitive impairment has been suggested in patients with
      carotid artery disease who have suffered from a TIA. The purpose of our study was
      to assess whether patients with carotid artery disease and TIAs are cognitively
      impaired, to describe the frequency, nature and severity of this impairment, and
      to search for associated patient characteristics.Thirty-nine consecutive patients
      with carotid occlusion and ipsilateral cerebral or retinal TIAs, and 46 healthy
      controls underwent extensive neuropsychological assessment. Performances were
      compared group-wise with analysis of variance. In addition, the presence of
      cognitive impairment in the individual patient was determined. Associations
      between illness characteristics and cognitive impairment were explored with
      regression analysis.Fifty-four percent of patients were cognitively impaired.
      Cognitive deficits were non-specific in nature and mild in severity. Impairment
      occurred also in patients with isolated retinal symptoms and in those without
      visible ischemic brain lesions on MRI. Neither the presence of any vascular risk
      factor, the side of the symptomatic carotid occlusion, the uni- or bilaterality
      of carotid occlusion, nor the number of cerebral ischemic lesions were predictors
      of cognitive impairment. We conclude that about half of the patients with carotid
      artery occlusion and ipsilateral TIAs are cognitively impaired. The presence of
      cognitive deficits in patients with isolated retinal symptoms and in those
      without cerebral ischemic lesions on MRI argues against an exclusive role for
      structural brain damage in the pathogenesis of these deficits.

PMID- 14648152
TI  - MRI findings in central nervous system systemic lupus erythematosus are
      associated with immunoserological parameters and hypertension.
AB  - Involvement of the brain is one of the most important complications of systemic
      lupus erythematosus (SLE). To investigate the correlation between abnormal
      cranial MRI findings and age, duration of SLE, neuropsychiatric (NP)
      manifestations, hypertensive status, and the presence of antiphospholipid
      antibodies (PA) in patients with SLE we evaluated the MRI results of 81 SLE
      patients in nine NP clinical subgroups.Immunoserological status was described by
      the presence of lupus anticoagulant (LA), and anticardiolipin antibodies (aCL).
      The MRI findings were categorized as normal [41], cerebral atrophy [15], small
      subcortical hyperintensity [7], and infarct larger than 10mm [18]. Mean age
      differed among the clinical subgroups (ANOVA, p = 0.002), whereas there was no
      age difference among the subgroups based on MRI and immunoserological results.
      Patients with hypertension (33/81) were a mean of 6 years older at the time of
      examination (p = 0.033) and had stroke more frequently, than normotensive ones (p
      = 0.0015). MRI abnormalities were more frequent in patients with LA positivity (p
      < 0.01) than in those without these antibodies, and in the hypertensive than in
      the normotensive subgroup (p = 0.00041). The presence of PA was associated with
      abnormal MRI even after controlling for the effect of age and hypertensive status
      (p = 0.011). In our study the MRI findings in central nervous system SLE were
      independent of the age of patients and the age at the diagnosis of SLE, and were
      not influenced by the duration of SLE; however, they were associated with
      immunoserological parameters and hypertension.

PMID- 14648153
TI  - Clinical significance of recurrent psychogenic nonepileptic seizure status.
AB  - To explore the clinical significance of a history of recurrent psychogenic
      nonepileptic seizure status (PNES-status), this study describes the frequency of
      PNES-status in 85 consecutive PNES patients and examines whether there are
      relevant differences between patients with a history of recurrent PNES-status and
      other PNES-patients. PNES patients were also compared with 64 patients with
      epilepsy. Data were extracted from hospital records and a postal questionnaire
      (Dimensional Assessment of Personality Pathology-Basic Questionnaire; Screening
      for Somatoform Symptoms; Dissociative Experience Scale). Of the PNES-patients,
      77.6% reported at least one seizure > 30 minutes (PNES-status), 27 % admission to
      intensive care with status. 38.8% reported recurrent hospital admissions with
      status (PNES-status group), the remaining patients served as PNES-controls. The
      only clinical difference between the two PNES groups was that status patients
      were younger than PNES-controls (mean age 20.3 vs. 30.3 years, p = 0.001). Our
      results suggest that PNES status is common and often unrecognised. There were no
      substantial psychometric differences between patients with recurrent PNES-status
      and other PNES patients although both PNES-groups had more abnormal somatisation,
      dissociation and personality scores than patients with epilepsy.

PMID- 14648154
TI  - Stroke unit versus neurology ward--a before and after study.
AB  - INTRODUCTION: Few studies have tested the hypothesis of whether the beneficial
      effect of Stroke Units (SUs) can be reproduced in routine clinical practice and
      whether SU are also superior to neurological wards [NWs]. We aimed to compare the
      outcomes of patients of a newly implemented SU to the outcomes of patients
      hospitalized in a NW. METHODS: We made a before-after comparison of 352 SUs and
      352 NWs patients after adjusting for case-mixes by the multivariate method.
      Subgroup analyses were also performed to evaluate which patient groups benefit
      the most. In-hospital case-fatality, proportion of independent patients at
      discharge, length of hospital stay (LOHS), medical complication rate were the
      main outcome measures. RESULTS: Adjusted in-hospital case fatality was
      significantly reduced in the SUs (OR: 0.44, 95 % CI: 0.26-0.76; p = 0.003). The
      proportion of independent patients at discharge and patients having medical
      complications was not different. Length of hospital stay was shorter in SU
      patients (13.76 days vs. 16.72 days, p = 0.003). Treatment in the SUs decreased
      case fatality in many subgroups [men, elderly, early admitted, severe stroke, co
      morbidity present and ischemic stroke groups]. DISCUSSION: The results of
      randomized trials in favor of SUs can be reproduced in routine clinical practice.
      The benefit of SU care seems to be more apparent with advancing age and
      increasing stroke severity. Stroke Unit seems to be a better alternative to an
      experienced NW.

PMID- 14648155
TI  - Stroke unit versus neurology ward--a short commentary.

PMID- 14648156
TI  - Good outcome in early pregnancy following direct thrombolysis for cerebral venous
      sinus thrombosis.

PMID- 14648157
TI  - Novel APP mutation V715A associated with presenile Alzheimer's disease in a
      German family.

PMID- 14648158
TI  - Brain hemorrhage as a complication of type I cryoglobulinemia vasculopathy.

PMID- 14648159
TI  - Progressive multifocal leucoencephalopathy presenting with Parkinsonism.

PMID- 14648160
TI  - Myorhythmia associated with Hodgkin's lymphoma.

PMID- 14648161
TI  - Lymphocytic hypophysitis presenting early in pregnancy.

PMID- 14648162
TI  - Paraneoplastic necrotizing myelopathy with hypertrophy of the cauda equina.

PMID- 14648163
TI  - Carl Wernicke (1848-1905).

PMID- 14648167
TI  - Extraction of gunshot residues from the larvae of the forensically important
      blowfly Calliphora dubia (Macquart) (Diptera: Calliphoridae).
AB  - Whole body concentrations of lead (Pb), barium (Ba) and antimony (Sb) were
      determined in larvae of the blowfly Calliphora dubia (Macquart) (Diptera:
      Calliphoridae) removed from a piece of beef shot and contaminated with gunshot
      residue and compared with the concentrations detected within larvae feeding on a
      control piece of beef. Whole larvae were taken into solution and analysed using
      inductively coupled plasma-mass spectrometry (ICP-MS). Significantly higher
      concentrations of Pb, Ba and Sb were detected within the larvae feeding on the
      shot piece of beef compared with larvae that were feeding on the control piece of
      beef. Initial results indicate that the concentrations of Pb and Sb within the
      larvae decrease as the duration of feeding increases, whereas Ba concentrations
      appear to increase, suggesting a bioaccumulation of Ba within the larvae. The
      second part of this experiment investigated the depuration of Pb, Ba and Sb from
      the larvae following removal of the gunshot residue source. A significant
      reduction in Pb, Ba and Sb concentrations within the larvae was observed
      following the transfer of larvae from the shot piece of beef to the control piece
      of beef.

PMID- 14648168
TI  - Skin analysis following dermal exposure to kerosene in rats: the effects of
      postmortem exposure and fire.
AB  - To evaluate the usefulness of skin analysis for the forensic examination of cases
      involving postmortem dermal exposure to kerosene and/or fire, an experimental
      study using rats was performed. Rats received dermal exposure to kerosene before
      or after death, and the effect of fire was determined by burning an area of
      exposed skin after death. Kerosene concentrations in skin and blood were
      determined by gas chromatography-mass spectrometry and microscopic observation
      was performed for skin samples. No differences were observed in skin kerosene
      levels between antemortem and postmortem exposure. Kerosene concentrations in
      mildly burned skin where the stratum corneum (SC) was retained were approximately
      84% compared to those in non-burned exposed skin, whereas concentrations in
      severely burned skin where the SC was almost completely burned off were 28% of
      non-burned skin. Even in non-exposed control skin 14% of the original kerosene
      concentrations could be detected, which was considered to be caused by
      contamination during the experimental protocol combined with kerosene's property
      of a high affinity for the SC. These results suggest that (1) skin analysis is
      useful in estimating the type of petroleum product involved in crimes or
      accidents even for postmortem exposure, (2) whether the SC is retained or not
      primarily determined the kerosene levels in burned skin, and (3) attention must
      be paid to evaluate the results obtained from skin samples in the light of the
      circumstances surrounding the case.

PMID- 14648169
TI  - Characterization of ancestral chromosome fusion points in the Indian muntjac
      deer.
AB  - Tandem fusion, a rare evolutionary chromosome rearrangement, has occurred
      extensively in muntjac karyotypic evolution, leading to an extreme fusion
      karyotype of 6/7 (female/male) chromosomes in the Indian muntjac. These fusion
      chromosomes contain numerous ancestral chromosomal break and fusion points. Here,
      we designed a composite polymerase chain reaction (PCR) strategy which recovered
      DNA fragments that contained telomere and muntjac satellite DNA sequence repeats.
      Nested PCR confirmed the specificity of the products. Two-color fluorescence in
      situ hybridization (FISH) with the repetitive sequences obtained and T2AG3
      telomere probes showed co-localization of satellite and telomere sequences in
      Indian muntjac chromosomes. Adjacent telomere and muntjac satellite sequences
      were also seen by fiber FISH. These data lend support to the involvement of
      telomere and GC-rich satellite DNA sequences during muntjac chromosome fusions.

PMID- 14648170
TI  - Cosmic radiation and cancer mortality among airline pilots: results from a
      European cohort study (ESCAPE).
AB  - Cosmic radiation is an occupational risk factor for commercial aircrews. In this
      large European cohort study (ESCAPE) its association with cancer mortality was
      investigated on the basis of individual effective dose estimates for 19,184 male
      pilots. Mean annual doses were in the range of 2-5 mSv and cumulative lifetime
      doses did not exceed 80 mSv. All-cause and all-cancer mortality was low for all
      exposure categories. A significant negative risk trend for all-cause mortality
      was seen with increasing dose. Neither external and internal comparisons nor
      nested case-control analyses showed any substantially increased risks for cancer
      mortality due to ionizing radiation. However, the number of deaths for specific
      types of cancer was low and the confidence intervals of the risk estimates were
      rather wide. Difficulties in interpreting mortality risk estimates for time
      dependent exposures are discussed.

PMID- 14648172
TI  - Connection between human leucocyte antigens D region and T helper cytokines in
      preeclampsia.
AB  - Preeclampsia is a common and major cause of maternal and perinatal morbidity and
      mortality. Human leucocyte antigen (HLA) susceptibility and impaired adaptation
      of the T lymphocyte sub-population and a bi-directional effect of T helper
      cytokines on the outcome of pregnancy have been reported in patients with
      preeclampsia. The association between maternal HLA class II and T helper
      cytokines in women with preeclampsia was investigated in seventy-six preeclamptic
      women and normotensive controls using Terasaki microlymphocytotoxicity test. T
      helper cytokines interleukin (IL)-8, IL-6, IL-4, tumour necrosis factor (TNF)
      alpha and interferon (IFN)-gamma were estimated in the maternal blood and
      placenta by enzyme-linked immunosorbent assay (ELISA). Histopathological
      evaluation of the placenta was also carried out. HLA class II DR2, DR4, DR5,
      DRw8, DRw10, DRw11, DRw18, and DQw2 had significant relative risk ratios for
      preeclampsia, while DQw3 was more common in the controls. DR4-DRw11-DQw2
      haplotype was more common in preeclamptic women with intrauterine growth
      restriction, low birth weight and placental weight, increased expression of T
      helper cytokines IL-8, TNF-alpha and IFN-gamma and abnormal uteroplacental
      vasculature. These findings suggest that HLA class II DR4-DRw11 -DQw2 haplotypes
      may be associated with preeclampsia with intrauterine growth restriction through
      low placental weight from impaired placental development, as a result of
      increased expression of T helper 1 cytokines IL-8, TNF-alpha and IFN-gamma.

PMID- 14648173
TI  - A retrospective study of unplanned out-of-hospital deliveries.
AB  - Our objective was to determine maternal characteristics and perinatal outcome of
      unplanned unattended deliveries en route to the hospital in comparison to
      unplanned deliveries attended by medical personnel within the parking facility of
      the hospital. All singleton deliveries occurring between 1988 and 1999 were
      analyzed from the computerized perinatal database. Maternal characteristics and
      pregnancy outcome of unattended, unplanned out-of-hospital births were compared
      with unplanned deliveries in the hospital parking lot, with the assistance of
      medical personnel. Out of 2328 out-of-hospital deliveries, 5.7% ( n=133) were
      managed by medical personnel in the parking lot and 94.3% ( n=2195) occurred en
      route to the hospital. The birth weight of newborns from the attended out-of
      hospital delivery group was significantly higher than the comparison group
      (3126.2+/-516 g vs. 3019+/-522 g; P=0.023). A significant linear association was
      found between birth weight and attended out-of-hospital births (Mantel-Haenszel
      test for linear association; P=0.002). Moreover, these newborns were
      significantly more likely to be large for gestational age (OR=2.2, 95% CI 1.2
      3.9; P=0.004). Parturients who delivered in the parking lot with the assistance
      of medical personnel, had significantly higher rates of grade 2 perineal tears
      (OR=8.4, 95% CI 1.1-5.4; P=0.041). Perinatal mortality was non-significantly
      higher among attended out-of-hospital deliveries (OR=2.8, 95% CI 0.8-8.3;
      P=0.279) as compared to unattended out-of-hospital deliveries. The attendance of
      medical personnel in unplanned out-of-hospital deliveries did not influence the
      birth outcome.

PMID- 14648174
TI  - Hypermobility syndrome in 105 women with pure urinary stress incontinence and in
      105 controls.
AB  - We compared the frequency of Hypermobility Syndrome (HS) in 105 patients with
      urinary stress incontinence (USI) with the frequency of HS in 105 healthy
      controls that matched for age and parity. A Beighton score (BS) of more than 3
      was used to make the clinical diagnosis of HS. Thirty-six patients (34.28%) from
      the USI group and 28 patients (26.66%) from the control group were diagnosed as
      HS. The mean BS values were 6.44+/-0.35 and 5.21+/-0.29 respectively. The
      difference between the two groups was statistically significant ( P<0.05).

PMID- 14648175
TI  - Comparative profiling of metabolism-related gene expression in pre-eclamptic and
      normal pregnancies.
AB  - Extensive endothelial dysfunction has been regarded as the central hallmark in
      the pathogenesis of pre-eclampsia, but the mechanisms leading to this dysfunction
      remain unclear. The levels of many metabolism substances, such as lipid
      peroxides, are changed in plasma of patients with pre-eclampsia. Some of those
      might be associated with the occurrence of pre-eclampsia. Our research was trying
      to reveal the source of metabolism substances which were elevated in plasma of
      preeclamptic patients. The expression of many metabolism-associated genes in 3
      preeclamptic and strictly matched 3 normal placentas were compared by employing
      DNA chip representing 243 human hormone-associated genes. The results showed
      that, many redox metabolism-related genes (GenBank: U78168, X16699, D32143,
      AL035079, AF069668, X53463, J03746, X02317, X91247, etc) were found more highly
      expressed in preeclamptic placenta than that in normal placenta. Additionally,
      the mRNA levels of some genes which were related to other metabolism such as
      hormone (GenBank: NM_001718, Z22535, M38180, M76665, X75252, J03258, U56725),
      were also higher in placenta of patients with pre-eclampsia. Furthermore, many
      transcription factor genes were also up-regulated in pre-eclampsia. It suggested
      that, the change of genes expression in placenta was associated with the change
      of metabolism in patients with pre-eclampsia.

PMID- 14648176
TI  - Results of TVT operations alone and combined with other vaginal surgical
      procedures.
AB  - We made a study of 61 women with genuine stress incontinence (GSI). They all had
      a tension-free vaginal tape (TVT) and 28 patients had concomitant vaginal
      surgery. The cure rates and complication rates for the two groups were similar.

PMID- 14648177
TI  - Socioeconomic factors and cervical cancer mortality in Spain during the period
      1989-1997.
AB  - METHODS: A study was made of cervical cancer (CC) mortality trends in Spain
      during the period 1989-1997 at National, Autonomous Community and Provincial
      levels, in relation to different socioeconomic factors. Data were obtained from
      the Spanish National Institute of Statistics (Instituto Nacional de Estadistica,
      INE). The crude mortality rates were age-adjusted using the indirect method and
      Gross Domestic Product (GDP) as socioeconomic status (SES) indicator. RESULTS:
      National CC age-adjusted mortality rates have increasing slightly, varying from
      3.09 deaths/100000 women in 1989 to 3.42 in 1996. The highest age-adjusted
      mortality rates corresponded to Seville, Palencia and Orense, with 4.13, 4.06 and
      3.98 cases/100000 women, respectively. The lowest mortality rates were found in
      Las Palmas, Cantabria and Alicante with 2.63, 2.77 and 2.80 deaths/100000 women,
      respectively. A relative risk (RR) of 1.14 (95%CI: 0.98-1.32) ( P=0.048) was
      observed between the provinces with the lowest SES and highest mortality rate,
      and those with the highest SES and lowest mortality rate. CONCLUSION: The results
      of our study show a slight increasing trend in CC mortality rates in Spain during
      the period 1989-1997, and suggest that the variations among provinces and
      Autonomous Communities could be due to CC risk factors (SES related to human
      papillomavirus, parity, diet, etc.) and differences in early diagnosis.

PMID- 14648178
TI  - Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and
      cdk4) in human endometrial cancer: correlation with clinicopathological features.
AB  - INTRODUCTION: Derailments of the control mechanisms in the G1/S phase of the cell
      cycle play a fundamental role in the initiation and progression of cancer.
      However, only a few reports have addressed the issue of simultaneously occurring
      abnormalities of Rb-pathway components in malignant endometrial tumors. METHODS:
      Currently, we assessed the expression of cell-cycle regulatory proteins (pRb,
      cyclin D1, p16(INK4A) and cdk4) in 48 sporadic endometrial cancers, and
      investigated these tumors for a possible relationship between aberrant protein
      staining and clinicopathological variables of cancer and RB-LOH. RESULTS: There
      was abnormal pRb, cyclin D1, p16(INK4A) and cdk4 immunoreactivity in 2%, 50%, 6%
      and 25% of cases, respectively. Altogether, 33 of 48 (69%) endometrial malignant
      tumors showed abnormal expression of at least one Rb-pathway protein
      immunohistochemically. However, there was significant correlation neither between
      the cell-cycle regulators nor between the frequency of pRb, p16(INK4A) and cyclin
      D1 abnormalities and clinicopathological variables of cancer, but a significant
      correlation did exist between cdk4 staining and the clinical stage of disease (
      P<0.05, Fisher's exact test). Moreover, an inverse relationship was also
      demonstrated between cdk4 expression and patient age ( r=-0.367; P=0.01).
      However, none of the cell-cycle regulatory proteins, except for pRb, was related
      to loss of heterozygosity at locus 13q14. CONCLUSION: As a conclusion,
      derailments of the Rb-pathway components, cyclin D1 and cdk4 in particular, seems
      to participate in the endometrial cancer development in humans. Overexpression of
      cdk4 was related to the progression of neoplastic disease and corresponds with
      age of onset, suggesting a major role of altered cdk4 immunoreactivity in the
      progression of endometrial cancer.

PMID- 14648179
TI  - Birthweight percentiles by gestational age in Kuwait.
AB  - Our aim is develop a curve for singleton birthweight based on accurately
      calculated gestational age. A retrospective analysis of all singleton live births
      from 22-44 completed weeks of gestation during the period from September 1998 to
      December 2000 in the two largest birth birth centers in Kuwait was conducted.
      Neonates with major congenital anomalies and those with unrecorded gestational
      age were excluded from the study population. Total population and gender-specific
      birthweight percentiles according to gestational age were developed after
      smoothening of growth curves. A total of 35768 births were included in the
      development of the birthweight curve. Percentiles of birthweight for all
      population and by gender are presented. There was significant difference in
      birthweight among different ethnic groups in this population. At term, 9.8% of
      births are smaller than the 10th percentile and 10.0% are larger than the 90th
      percentile. Plotting birthweight in our population on percentile curves derived
      from the United States or United Kingdom would generally overestimate small for
      gestational age newborns and underestimate large for gestational age newborns. We
      conclude that the diagnosis of clinically significant birthweight abnormalities
      depends on the fetal growth curve used. A population specific curve of fetal
      growth dated by ultrasonography would provide a reliable reference for
      birthweight distribution.

PMID- 14648180
TI  - A prospective, double-blind, randomized, placebo-controlled clinical trial of
      bromocriptin in clomiphene-resistant patients with polycystic ovary syndrome and
      normal prolactin level.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of of
      bromocriptin combined with clomiphene citrate in clomiphene-resistant patients
      with polycystic ovary syndrome and normal prolactin level. DESIGN: Prospective,
      double-blind, controlled study. SETTING: University teaching hospital. PATIENTS:
      One hundred polycystic ovary patients and normal prolactin (PRL) who were
      clomiphene citrate resistant. INTERVENTIONS: Treatment group received 150 mg
      clomiphene citrate on days 5-9 and 7.5 mg bromocriptin continuously. Control
      group received the same protocol of clomiphene citrate combined with placebo.
      MAIN OUTCOME MEASURES: Hormonal status, follicular monitoring, ovulation rate.
      RESULTS: Follicular development (follicular size greater than 15 mm) was observed
      in 12 (25.5%) and eight (15.1%) women in treatment and placebo group respectively
      ( P=0.29). The serum prolactin level was within normal limits in all patients
      before treatment. After 3 and 6 months of treatment with bromocriptin, there was
      a significant decrease in serum level of prolactin ( P=0.000001). No any
      significant differences was seen in ovulation, and serum levels of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone
      sulfate (DHEAS), progesterone (P) between treatment and placebo group after
      treatment. CONCLUSIONS: The only significant effect of long-term bromocriptin
      therapy in clomiphene citrate resistant polycystic ovary women was to lower the
      serum prolactin concentration. It was also concluded that 10-15% of patients with
      polycystic ovaries experienced occasional ovulatory cycles and pregnancy whether
      or not they were on treatment.

PMID- 14648181
TI  - Maternal postpartum group B beta-hemolytic streptococcus ventriculoperitoneal
      shunt infection.
AB  - BACKGROUND: Women with cerebrospinal fluid shunts require special management
      during the course of pregnancy. CASE REPORT: We describe a case of delayed
      postpartum ventriculoperitoneal shunt infection by Group B streptococcus in a 19
      year-old who presented complaining of headache and a fever. The CSF culture from
      the shunt tap and the distal shunt tip both grew Group B beta-hemolytic
      streptococcus. CONCLUSION: Women who are colonized with Group B streptococcus and
      who have cerebrospinal fluid shunts should receive perinatal antibiotic
      prophylaxis, and may require more extended prophylactic antibiotics with cesarean
      section deliveries to prevent catheter tip colonization and subsequent shunt
      infection.

PMID- 14648182
TI  - Prenatal three-dimensional ultrasound diagnosis of a camptomelic dysplasia.
AB  - We describe a case of camptomelic dysplasia identified prenatally with the
      assistance of three-dimensional ultrasonography. The typical skeletal dysplasia
      of camptomelic dysplasia - including anterior bowing of the tibia, with skin
      dimpling over a convex surface at the point of maximal deformity, and talipes
      equinovarus - was successfully identified using the techniques of surface
      rendering, multiplanar displays and rotated volume data. Three-dimensional
      ultrasonography allows the diagnosis of camptomelic dysplasia, which has a poor
      prognosis as it is accompanied by respiratory insufficiency and spinal
      deformities, to be made without delay and provides information supplementary to
      that provided by two-dimensional ultrasound for early diagnosis of skeletal
      dysplasia.

PMID- 14648183
TI  - Massive fetomaternal hemorrhage and oxytocin contraction test: case report and
      review.
AB  - We present a case of a nulliparous woman who underwent oxytocin contraction test
      because of abnormal cardiotocograph. She delivered a severely anemic neonate due
      to severe fetomaternal hemorrhage. Fetal ultrasonography and Doppler studies of
      the umbilical arteries may not be helpful, while its worthy to perform flow
      cytometry for detection of fetal cells in maternal circulation when there is
      strong clinical suspicion. Management of massive fetomaternal hemorrhage requires
      immediate delivery by Caesarean section if the gestational age is suitable.
      Alternatively, for very premature fetuses could be used serial fetal
      intravascular transfusions if there are the necessary facilities and experienced
      personnel.

PMID- 14648184
TI  - Thyroid hormone resistance and enlargement of the sella turcica during pregnancy.
AB  - CASE REPORT: A 26-year-old pregnant woman was admitted to our institution running
      her 30 weeks of gestation. The patient had a past history of total thyroidectomy
      cause of a thyroid papillary carcinoma and presented with increased
      supraphysiological TSH levels under 250 microg T4, while slightly hyperthyroid,
      from the clinical point of view. Partial resistance to thyroid replacement
      therapy or TSH-secreting tumour was evoked. Pituitary MRI revealed a pituitary
      enlargement without excluding a pituitary adenoma. To avoid further stress on
      pituitary a caesarean section was performed at 38 weeks of gestation. MRI 7
      months later was normal, while the patient remained under high doses of T4
      replacement therapy and TSH was found at the upper limits of normalcy, while T3,
      T4 and FTI were above normalcy. CONCLUSION: We conclude that, in the absence of
      thyroid gland, high TSH levels due to thyroid hormone resistance could be
      erroneously attributed to a pituitary TSH secreting tumour, when associated with
      a pregnancy-related pituitary enlargement.

PMID- 14648185
TI  - Asymptomatic pelvic Castleman disease in an infertile woman: case report.
AB  - Castleman disease is defined as angiofollicular benign lymph node hyperplasia
      usually found in the mediastinum. Pelvic lymph node involvement is very rare. We
      now report a case of asymptomatic intrapelvic Castleman disease found by chance
      in an infertile woman. Transvaginal ultrasonography is very useful in diagnosing
      the disease. After 7 years of follow-up, the patient is free from recurrence.

PMID- 14648186
TI  - Successful salvage therapy of resistant gestational trophoblastic disease with
      etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP).
AB  - A 26-year-old woman who had been treated for nonmetastatic gestational
      trophoblastic tumor with three courses of methotrexate with folinic acid rescue
      and had been lost to follow up for 4 years was referred with the fractional
      curettage diagnosis of choriocarcinoma that had been performed for abnormal
      vaginal bleeding. Her serum beta human chorionic gonadotropin (betahCG) was
      706000 mIU/mL and there were multiple pulmonary metastatic foci. The uterus was
      12 weeks pregnant-size and a 6 x 6-cm tumor mass was seen within the anterior
      uterine wall at ultrasonography. Following total abdominal hysterectomy
      etoposide, methotrexate, actinomycin-D, vincristine and cyclophosphamide (EMA/CO)
      regimen was given. Whole brain radiation of 30 Gy in 3 weeks for brain
      metastasis, discovered in magnetic resonance imaging was given after the first
      course. Since serum betahCG levels plateaued after three courses of chemotherapy
      and multiple pulmonary metastases persisted, treatment was shifted to etoposide,
      methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP) regimen. She was in
      remission after three courses of chemotherapy.

PMID- 14648187
TI  - Laparoscopic bariatric surgery.

PMID- 14648188
TI  - Multimedia article. Laparoscopic Ladd's procedure in two adults: malrotation and
      the minimally invasive approach.
AB  - Malrotation is an intestinal rotation anomaly rarely diagnosed in adults. In the
      adult patient, obstructing peritoneal bands may lead to nausea and abdominal
      distention. Familiarity with this presentation as well as the aberrant anatomy
      associated with the unusual problem facilitates surgical treatment. While the
      minimally invasive approach requires meticulous dissection due to this abnormal
      anatomy, laparoscopic treatment does provide the advantages of short
      convalescence and low morbidity. This video briefly reviews embryologic
      intestinal development, rotational anomalies and two laparoscopic Ladd's
      procedures.

PMID- 14648191
TI  - Oviposition habitat selection in response to risk of predation in temporary
      pools: mode of detection and consistency across experimental venue.
AB  - Natural selection should favor females that avoid ovipositing where risk of
      predation is high for their progeny. Despite the large consequences of such
      oviposition behavior for individual fitness, population dynamics, and community
      structure, relatively few studies have tested for this behavior. Moreover, these
      studies have rarely assessed the mode of detection of predators, compared
      responses in prey species that vary in vulnerability to predators, or tested for
      the behavior in natural habitats. In an outdoor artificial pool experiment, we
      tested the oviposition responses of two dipteran species, Culiseta longiareolata
      (mosquito) and Chironomus riparius (midge), to the hemipteran predator, Notonecta
      maculata. Both dipteran species have similar life history characteristics, but
      Culiseta longiareolata larvae are highly vulnerable to predation by Notonecta,
      while Chironomus riparius larvae are not. As their vulnerabilities would suggest,
      Culiseta longiareolata, but not Chironomus riparius, strongly avoided ovipositing
      in pools containing Notonecta. An experiment in natural rock pools assessing
      oviposition by Culiseta longiareolata in response to Notonecta maculata yielded
      an oviposition pattern highly consistent with that of the artificial pool
      experiment. We also demonstrated that the cue for oviposition avoidance by
      Culiseta longiareolata was a predator-released chemical: Notonecta water (without
      Notonecta replenishment) repelled oviposition for 8 days. Oviposition avoidance
      and mode of detection of the predator have important implications for how to
      assess the true impact of predators and for the use of commercially produced
      kairomones for mosquito control.

PMID- 14648192
TI  - Implantation in vitro: co-culture of rat blastocyst and epithelial cell vesicles.
AB  - Implantation of blastocysts involves conversion of maternal and embryonic cell
      surfaces from a nonadhesive to an adhesive state in response to the internally
      driven developmental program or to externally generated factors. However, the
      intricacies of the cellular and subcellular changes that promote the attachment
      are not known, because these changes are difficult to determine in situ because
      of the nonaccessibility of the site. To overcome this, an in vitro model of
      implantation was developed by co-culturing rat blastocysts and uterine epithelial
      cells of the same gestational age (day 5 postcoitum; plug day as day 1) in drops
      hanging from the lid of a Petri dish. The system was used to study the changes on
      the surface membranes of the cells of the trophectoderm and uterine epithelium
      and to evaluate the antiadhesive activity of the newly designed test substances.
      The isolated epithelial cell vesicles were co-cultured with zona-free blastocysts
      in the microdrops (40-50 microl) hanging from the lid of a 60-mm Petri dish. The
      lid was placed over the lower dish, which was presaturated with the medium. The
      culture was examined 48 h later to determine the site of adhesion of epithelial
      cell vesicles with the trophoblasts lining the blastocyst. The cell-cell adhesion
      was monitored on a computerized image analyzer. To validate the adhesion of
      blastocysts and epithelial cell vesicles in co-culture, the expression of a cell
      adhesion molecule, uvomorulin, was studied using immunocytochemical technique
      after incubating with antiuvomorulin antibody. Intense staining was noted on the
      membrane surfaces at the site of attachment of the blastocyst and cell vesicles.

PMID- 14648193
TI  - Distribution of serotonin-like immunoreactive neurons in the slug Limax
      valentianus.
AB  - Immunohistochemical techniques were used to study the distribution of serotonin
      containing neurons in the nervous system of the slug Limax valentianus.
      Approximately 350 serotonin-like immunoreactive cell bodies were found in the
      central nervous system. These were located in the cerebral, pedal, visceral and
      right parietal ganglia. Most serotonin-like immunoreactive neurons had small cell
      bodies, which were aggregated into discrete clusters. A pair of previously
      identified metacerebral giant cells were found on the anterior side of the
      cerebral ganglion, and two additional pairs of uniquely identifiable, serotonin
      like immunoreactive cells were found on the posterior side of the cerebral
      ganglion. The whole-mount maps of these stained neurons will be useful in further
      physiological and biochemical studies of olfactory learning at the cellular level
      in Limax valentianus.

PMID- 14648194
TI  - Human periapical granulation tissue contains osteogenic cells.
AB  - Bone defects caused by periapical inflammation can be treated and improved by
      endodontic therapy. However, the mechanism for osseous healing of periapical
      lesions after root canal treatment is unclear. In this study we examined whether
      fibroblastic cells from human periapical granulation tissue could produce
      calcified matrix in vitro. Periapical lesions from three patients were dissected
      in endodontic surgery, and fibroblastic cells (HFC) migrating from these lesions
      in vitro were used in this study. The HFC were cultured with or without beta
      glycerophosphate (beta-GP) and ascorbic acid (AA), and the expression of human
      runt-related transcription factor-2 (Runx2), osterix (Osx), osteopontin (Opn),
      and osteocalcin (Ocn) mRNA, and alkaline phosphatase (ALPase) was examined by
      reverse transcriptase-polymerase chain reaction (RT-PCR) or by an enzyme
      cytochemical technique. Furthermore, calcification in the cells was investigated
      by von Kossa staining. At the beginning of the culture, HFC expressed Runx2 mRNA
      faintly, but neither Opn mRNA nor ALPase activity. Immunocytochemical study also
      showed HFC expressed Runx2 more weakly, compared to SaOS2. However, the
      expression levels of ALPase, and Runx2, Osx, and Opn mRNA, were stimulated by 2
      mM beta-GP and 50 microg/ml AA. After 4 weeks of culture with 2 mM beta-GP and 50
      microg/ml AA, HFC formed von Kossa staining-positive calcified deposits on
      culture dishes, and also expressed Ocn mRNA. These results suggest that inflamed
      periapical granulation tissue contains osteogenic cells that have the potential
      to differentiate into mature osteoblastic or cementoblastic cells, and that such
      cells might contribute to osseous healing after root canal treatment.

PMID- 14648195
TI  - Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures.
AB  - Demonstration of the importance of the paired box transcription factor Pax7 for
      the murine myosatellite cell population, with persistent expression in mature
      skeletal muscle, prompted us to investigate the distribution of Pax7 protein in
      biopsy samples of normal and pathological human skeletal limb muscle.
      Immunostaining for M-cadherin, an adhesion molecule present at the interface
      between myofibre and satellite cell, and the characteristic position adjacent to
      the muscle fibre and beneath the fibre's basement membrane were used to identify
      satellite cells. Anti-Pax7 reactivity was found in the majority of satellite
      cells but a small population was Pax7 negative. Neither could we identify Pax7
      positive nuclei in freshly regenerating myotubes or in presumed myoblasts in
      these biopsies. Similarly, in myogenic cell cultures derived from the
      explantation of human foetal muscle Pax7 expression was low or undetectable at
      the proliferative myoblast stage but it became prominent in an increasing
      proportion of mononucleate cells after the induction of differentiation. This
      expression was, however, restricted to mononucleate cells; it did not persist
      into the differentiation stage of newly formed multinucleate myotubes. Despite
      this, in the biopsy samples, we occasionally found Pax7-positive nuclei in muscle
      fibres that seemed to be undergoing degenerative changes. Most of these were
      found to be the nuclei of cells engaged in focal regenerative processes, but Pax7
      re-expression by myonuclei "in distress" cannot be ruled out entirely.

PMID- 14648196
TI  - Small deletions disturb desmin architecture leading to breakdown of muscle cells
      and development of skeletal or cardioskeletal myopathy.
AB  - Desmin ( DES) mutations have been recognized as a cause of desmin-related
      myopathy (OMIM 601419), or desminopathy, a disease characterized by progressive
      limb muscle weakness and accumulation of desmin-reactive granular aggregates in
      the myofibers. We have studied three families with skeletal or cardioskeletal
      myopathy caused by small in-frame deletions in the desmin gene. The newly
      identified in-frame deletions E359_S361del and N366del alter the heptad
      periodicity within a critical 2B coiled-coil segment. Structural analysis reveals
      that the E359_S361 deletion introduces a second stutter immediately downstream of
      the naturally occurring stutter, thus doubling the extent of the local coiled
      coil unwinding. The N366del mutation converts the wild-type stutter into a
      different type of discontinuity, a stammer. A stammer, as opposed to a stutter,
      is expected to cause an extra overwinding of the coiled-coil. These mutations
      alter the coiled-coil geometry in specific ways leading to fatal damage to desmin
      filament assembly. Expression studies in two cell lines confirm the inability of
      desmin molecules with this changed architecture to polymerize into a functional
      filamentous network. This study provides insights into molecular pathogenetic
      mechanisms of desmin mutation-associated skeletal and cardioskeletal myopathy.

PMID- 14648197
TI  - Pyruvate decarboxylases from the petite-negative yeast Saccharomyces kluyveri.
AB  - Saccharomyces kluyveri is a petite-negative yeast, which is less prone to form
      ethanol under aerobic conditions than is S. cerevisiae. The first reaction on the
      route from pyruvate to ethanol is catalysed by pyruvate decarboxylase, and the
      differences observed between S. kluyveri and S. cerevisiae with respect to
      ethanol formation under aerobic conditions could be caused by differences in the
      regulation of this enzyme activity. We have identified and cloned three genes
      encoding functional pyruvate decarboxylase enzymes (PDCgenes) from the type
      strain of S. kluyveri (Sk- PDC11, Sk- PDC12 and Sk- PDC13). The regulation of
      pyruvate decarboxylase in S. kluyveri was studied by measuring the total level of
      Sk- PDC mRNA and the overall enzyme activity under various growth conditions. It
      was found that the level of Sk- PDC mRNA was enhanced by glucose and oxygen
      limitation, and that the level of enzyme activity was controlled by variations in
      the amount of mRNA. The mRNA level and the pyruvate decarboxylase activity
      responded to anaerobiosis and growth on different carbon sources in essentially
      the same fashion as in S. cerevisiae. This indicates that the difference in
      ethanol formation between these two yeasts is not due to differences in the
      regulation of pyruvate decarboxylase(s), but rather to differences in the
      regulation of the TCA cycle and the respiratory machinery. However, the PDC genes
      of Saccharomyces/ Kluyveromyces yeasts differ in their genetic organization and
      phylogenetic origin. While S. cerevisiae and S. kluyveri each have three PDC
      genes, these have apparently arisen by independent duplications and
      specializations in each of the two yeast lineages.

PMID- 14648198
TI  - DSC1-MCB regulation of meiotic transcription in Schizosaccharomyces pombe.
AB  - Meiosis is initiated from the G1 phase of the mitotic cell cycle, and consists of
      pre-meiotic S-phase followed by two successive nuclear divisions. Here we show
      that control of gene expression during pre-meiotic S-phase in the fission yeast
      Schizosaccharomyces pombe is mediated by a DNA synthesis control-like
      transcription factor complex (DSC1), which acts upon M lu1 cell cycle box (MCB)
      promoter motifs. Several genes, including rec8+, rec11+, cdc18+, and cdc22+,
      which contain MCB motifs in their promoter regions, are found to be co-ordinately
      regulated during pre-meiotic S-phase. Both synthetic and native MCB motifs are
      shown to confer meiotic-specific transcription on a heterologous reporter gene. A
      DSC1-like transcription factor complex that binds to MCB motifs was also
      identified in meiotic cells. The effect of mutating and over-expressing
      individual components of DSC1 (cdc10+, res1+, res2+, rep1+ and rep2+) on the
      transcription of cdc22+, rec8+ and rec11+ during meiosis was examined. We found
      that cdc10+, res2+, rep1+ and rep2+ are required for correct meiotic
      transcription, while res1+ is not required for this process. This work
      demonstrates a role for MCB motifs and a DSC1-like transcription factor complex
      in controlling transcription during meiosis in fission yeast, and suggests a
      mechanism for how this specific expression occurs.

PMID- 14648199
TI  - Identification of proteins that interact with two regulators of appressorium
      development, adenylate cyclase and cAMP-dependent protein kinase A, in the rice
      blast fungus Magnaporthe grisea.
AB  - Adenylate cyclase (MAC1) and the catalytic subunit of cAMP-dependent protein
      kinase A (CPKA) are required for appressorium development and pathogenesis in the
      rice blast pathogen Magnaporthe grisea. To identify new components in the cAMP
      signal transduction pathway, we used the yeast two-hybrid system to screen MAC1
      and CPKA against an appressorium cDNA library. The cDNA library was constructed
      by GATEWAY recombinational cloning, enabling transfer of the library to various
      alternative vectors. The protein phosphatase domain in MAC1, which is unique to
      fungal adenylate cyclases, interacted with a MAP kinase kinase and a Ser/Thr
      kinase. Interactions of MAC1 with the kinases may prove to be part of feedback
      loops between the corresponding signaling pathways. A predicted membrane protein,
      ACI1, which is highly expressed under conditions that are conducive to
      appressorium formation, also interacted with MAC1. ACI1 has an extracellular
      domain containing eight-cysteines, which is also present in other fungal proteins
      implicated in pathogenesis. The N-terminal half of CPKA, which includes a
      glutamine-rich sequence unique to a group of fungal sequences, interacted with a
      putative transcriptional regulator and two different glycosyl hydrolases.
      Phosphorylation motifs in these sequences suggest that they could be CPKA
      substrates. The protein interaction assay employed here can now be scaled up to
      identify interactions between a larger set of proteins in the M. grisea
      interactome.

PMID- 14648200
TI  - Nuclear import of yeast Gcn4p requires karyopherins Srp1p and Kap95p.
AB  - The yeast transcription factor Gcn4p contains two stretches of amino acid
      residues, NLS1 and NLS2, which are independently able to relocate the cytoplasmic
      protein chorismate mutase into the nucleus. Only NLS2 is conserved among fungi. A
      truncated version of CPCA (the counterpart of Gcn4p in Aspergillus nidulans),
      which lacks the conserved NLS, accumulates in the cytoplasm instead of the
      nucleus. Nuclear uptake mediated by the NLS1 of Gcn4p is impaired by defects in
      genes for several different karyopherins, whereas NLS2-dependent nuclear import
      specifically requires the alpha-importin Srp1p and the beta-importin Kap95p.
      Yeast strains that are defective in either of these two karyopherins are unable
      to respond to amino acid starvation. We have thus identified Gcn4p as a substrate
      for the Srp1p/Kap95p transport complex. Our data suggest that NLS2 is the
      essential and specific nuclear transport signal; NLS1 may play only an unspecific
      or accessory role.

PMID- 14648201
TI  - Evidence for control of nitrogen metabolism by a START-dependent mechanism in
      Saccharomyces cerevisiae.
AB  - It is generally thought that cell growth and metabolism regulate cell division
      and not vice versa. Here, we examined Saccharomyces cerevisiae cells growing
      under conditions of continuous culture in a chemostat. We found that loss of G1
      cyclins, or inactivation of the cyclin-dependent kinase Cdc28p, reduced the
      activity of glutamate synthase (Glt1p), a key enzyme in nitrogen assimilation. We
      also present evidence indicating that the G1 cyclin-dependent control of Glt1p
      may involve Jem1p, a DnaJ-type chaperone. Our results suggest that completion of
      START may be linked to nitrogen metabolism.

PMID- 14648202
TI  - Comparative mapping reveals partial conservation of synteny at the apomixis locus
      in Paspalum spp.
AB  - In plants, gametophytic apomixis is a form of asexual reproduction that leads to
      the formation of seed-derived offspring that are genetically identical to the
      mother plant. A common set of RFLP markers, including five rice anchor markers
      previously shown to be linked to apomixis in Paspalum simplex, were used to
      detect linkage with apomixis in P. notatum and P. malacophyllum. A comparative
      map of the region around the apomixis locus was constructed for the three
      Paspalum species, and compared to the rice map. The locus that controls apomixis
      in P. simplex was almost completely conserved in the closely related species P.
      malacophyllum, whereas it was only partially represented in the distantly related
      species P. notatum. Although strong synteny of markers was noted between this
      locus and a portion of rice chromosome 12 in both P. simplex and P.
      malacophyllum, the same locus in P. notatum was localized to a hybrid chromosome
      which carries markers that map to rice chromosomes 2 and 12. All three Paspalum
      species showed recombination suppression at the apomixis locus; in the case of P.
      notatum, this might be due to a heterozygosity for a translocation that most
      probably negatively interferes with chromosomal pairing near the locus. A common
      set of markers that show linkage with apomixis in all three Paspalum species
      define a portion of the apomixis-controlling locus that is likely to contain
      genes critical for apomictic reproduction.

PMID- 14648203
TI  - Kinetics of change in the eotaxin concentration in serum and cerebrospinal fluid
      of mice infected with Angiostrongylus cantonensis.
AB  - The kinetics of changes in the eotaxin concentration in the serum and
      cerebrospinal fluid (CSF) of BALB/c mice after infection with Angiostrongylus
      cantonensis and the correlation between the concentration of eotaxin and worm
      recovery were investigated. The mean concentration of eotaxin in serum of
      infected mice gradually increased from 46.3+/-6.5 pg/ml at week 0 to 104.9+/-44.8
      pg/ml at week 3 after infection, while the mean eotaxin level in the CSF of
      infected mice rapidly increased from 18.7+/-2.1 pg/ml to 193.2+/-23.6 pg/ml 1
      week after infection and then increased further to 507.8+/-167.9 pg/ml at week 3.
      The concentrations of eotaxin in the CSF of infected mice each week after
      infection were all significantly higher than those in serum ( P<0.0001). In
      parallel with the increase in eotaxin in the CSF, infected mice showed gradual
      increases in CSF eosinophilia and a reduction in intracranial worm recovery. The
      concentration of eotaxin in CSF was higher in infected mice with more worms in
      the brain, except when the number of worms in the brain was >30. In addition,
      when the worm counts in the brains of infected mice were <30, eotaxin
      concentrations in the CSF were positively correlated with worm counts in the
      brain ( P<0.001). Thus, the release of eotaxin in the CSF of mice infected with
      A. cantonensis observed in this study was time dependent and worm-load dependent,
      and in parallel with the increase in eotaxin in the CSF, and gradual decreases in
      worm counts in the brains of infected mice.

PMID- 14648204
TI  - Sarcocystis spp. in birds of the order Anseriformes.
AB  - Having studied 342 birds of 20 species of the order Anseriformes, we found
      Sarcocystis cysts in 100 individuals (29.2+/-2.5%) belonging to 15 species. One
      macrocyst and four microcysts types have been determined. By means of light
      microscopy, the morphology of cyst walls and merozoites have been examined and
      morphometric data are presented. According to morphological features, macrocysts
      correspond to the S. rileyi species.

PMID- 14648205
TI  - Identification and specificity of a 38 kDa Loa loa antigenic fraction in sera
      from high-microfilaraemic Gabonese patients.
AB  - Circulating antigens isolated from sera of three high-microfilaraemic ( Loa loa)
      Gabonese patients were fractionated by gel filtration. A major component (38 kDa)
      was identified after SDS-PAGE and immunoblotting using sera of amicrofilaraemic
      patients with high level of antimicrofilariae Loa loa antibodies. The 38 kDa
      fraction was not found in the sera of parasitised patients or healthy controls.
      We looked for the 38 kDa antigen in the various stages of the filarial life cycle
      and found it in extracts of Loa loa microfilariae but not in somatic extracts of
      Loa loa male and female adult worms. This fraction could be used as a diagnostic
      marker in loiasis for amicrofilaraemic patients.

PMID- 14648206
TI  - Efficacy of an in-feed preparation of ivermectin against helminths in the
      European wild boar.
AB  - The wild boar is one of Europe's most popular game species and its densities are
      increasing. Management tools such as farm breeding, supplementary feeding, and
      translocations are more frequently employed and anthelmintics are increasingly
      used in game farms and translocations. Here, we report the results of a
      controlled slaughter study on the efficacy of an in-feed preparation of
      ivermectin in European wild boars naturally infected with various helminths. The
      efficacy of ivermectin against adult stages of Metastrongylus sp., Ascaris suum,
      Ascarops strongylina, Physocephalus sexalatus, and Simondsia paradoxa was 100%.
      Its efficacy against Oesophagostomum dentatum was 85.1%. There was no sufficient
      effect on Globocephalus urosubulatus, Trichuris suis, and Capillaria garfiai. The
      egg reduction in the treated group ( n=12) was 100% 6 days after the treatment.
      The importance of parasite surveillance and the application of anthelmintic
      treatments to wild boars in game farms or during translocations are discussed. We
      conclude that any attempt at helminth treatment in wild boars should consider the
      addition of a second compound with a more consistent effect on trichurids and
      other helminths.

PMID- 14648208
TI  - Report of a user-satisfaction analysis of a service provider for an oncology
      clinic.
AB  - PURPOSE: We used a questionnaire to assess professional user-satisfaction
      concerning the quality of services provided by a university hospital pharmacy for
      an oncology clinic. METHODS: All staff members at a major university medical
      center were given questionnaires pertaining to their satisfaction with various
      aspects of the services of the center's pharmacy department. The data analysis
      was carried out differentiating between the occupational groups and the various
      service sectors. RESULTS: Responding subjects (n = 460, 15% yield) were generally
      satisfied with the quality of all sections of the hospital pharmacy. Features
      appreciated included competence, reliability, flexibility, and rapid service, as
      well as helpfulness and friendliness. However, assessments differed among
      occupational groups: those working in the natural sciences tended to be most
      critical of pharmacy services, including availability of up-to-date information
      and speed of service. CONCLUSIONS: By surveying user-satisfaction, several
      shortcomings in the pharmacy ordering and complaint-management system were
      detected. Study findings should lead to improved service quality and will
      contribute to developing a manual for a quality management system (QMS).

PMID- 14648207
TI  - Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase
      (NAT) 2 polymorphisms and susceptibility to urothelial cancer.
AB  - PURPOSE: Arylamines are suspected to be the primary causative agent of urothelial
      cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a
      cytochrome P450 (CYP)1A2-catalyzed reaction, which produces a substrate for O
      esterification that can be catalyzed by N-acetyltransferases (NAT) or
      sulfotransferases (SULT). Recently, several polymorphisms of CYP1A2, SULT1A1, and
      NAT2 that affect their activities have been reported. METHODS: In this study, 306
      Japanese patients with urothelial transitional cell carcinoma and 306 healthy
      controls were compared for frequencies of CYP1A2, SULT1A1, and NAT2 genotypes.
      RESULTS: The frequencies of NAT2 intermediate or slow acetylator genotype were
      significantly higher in the urothelial cancer patients than in the healthy
      control subjects [odds ratio (OR) = 1.49, 95% confidence interval (95% CI) 1.06
      2.09, OR = 3.23, 95% CI 1.72-6.08, respectively]. Stratifying by amount of
      smoking, among subjects who consumed >33.5 pack-years and carried the SULT1A1
      *1/*1 or NAT2 slow acetylator genotype, the OR was 1.73 (95% CI 1.01-2.97)
      whereas it was 7.31 (95% CI 1.90-28.05) in non-smokers who carried the homozygous
      wild genotype, respectively. The relationships between CYP1A2, SULT1A1, and NAT2
      polymorphisms and clinical findings including tumor differentiation, stage, and
      recurrence rate were analyzed. Only associations between NAT2 genotype and
      pathological findings were admitted, and the higher OR of NAT2 intermediate and
      slow acetylator genotype was more likely to present to a low-grade tumor (G1)
      among heavy-smokers. CONCLUSIONS: Our results suggest that SULT1A1 *1/*1 and NAT2
      slow acetylator genotypes might modulate the effect of carcinogenic arylamines
      contained in tobacco smoke, and that the modulation of NAT2 intermediate and slow
      acetylator genotype has a tendency to present a higher risk for highly
      differentiated tumors among heavy-smokers.

PMID- 14648209
TI  - Clinical value of biliary alkaline phosphatase in non-jaundiced
      cholangiocarcinoma.
AB  - PURPOSE: Measurement of the activities of alkaline phosphatase isoenzyme has been
      used for the identification and monitoring of diseases associated with the
      isoenzyme. Biliary alkaline phosphatase (BALP), an isoform of liver-ALP, has been
      found in the serum of patients with biliary obstruction and metastatic liver
      cancer. This study compared the BALP isoform in the serum of patients with
      cholangiocarcinoma (CCA) with that of non-jaundiced benign hepatobiliary disease,
      other cancers, and healthy persons. METHODS: ALP isoforms were separated using
      cellulose acetate electrophoresis and the activity was demonstrated using indolyl
      blue reagent. RESULTS: The BALP isoform was demonstrated in 65% of CCA patients
      independently of jaundice condition or histological grading of the tumor. The
      level of serum BALP in non-jaundiced CCA was significantly lower than that of
      jaundiced CCA, and not correlated with serum bilirubin. No BALP was detected in
      healthy persons. In the patients with high serum ALP (> 147U/l), BALP can
      differentiate non-jaundiced CCA patients from other non-jaundiced carcinoma
      patients with 85% sensitivity, 79% specificity, and positive and negative
      predictive values of 81% and 83%, respectively. CONCLUSION: The demonstration of
      serum BALP, in particular in non-jaundiced patients with high serum ALP, may
      indicate the presence of tumor in the bile duct.

PMID- 14648210
TI  - Biweekly CHOP or THP-COP regimens in the treatment of newly diagnosed aggressive
      non-Hodgkin's lymphoma. A comparison of doxorubicin and pirarubicin: a randomized
      phase II study.
AB  - PURPOSE: To compare the efficacy and safety of a biweekly CHOP regimen consisting
      of cyclophosphamide (CPA), doxorubicin (DOX), vincristine (VCR), and prednisolone
      (PSL) and those of a biweekly THP-COP regimen containing pirarubicin (THP), an
      anthracyclin with less cardiotoxicity than DOX. METHODS: A prospective,
      randomized phase II study with 80 patients (40 receiving CHOP or THP-COP) less
      than 70 years of age with previously untreated aggressive non-Hodgkin's lymphoma
      (NHL). The regimens consisted of DOX or THP 50 mg/m2, CPA 750 mg/m2, VCR 1.4
      mg/m2, and PSL 100 mg/body administered for 5 days every 2 weeks for eight
      cycles. RESULTS: No significant differences in known prognostic factors were
      found between the two groups. Complete remission rate was 72.5% (72.5% for CHOP,
      72.5% for THP-COP). The 5-year overall survival rate was 49.2% (43.7% for CHOP,
      54.0% for THP-COP). When the patients were divided into groups with favorable or
      poor prognostic factors according to the International Prognostic Index, survival
      of the former group (L/LI) was superior to that of the later group (HI/H),
      regardless of chemotherapy regimen ( P < 0.001). Although grade 3 cardiotoxicity
      occurred in one patient in the CHOP group, no fatal toxic reactions occurred in
      either group. The THP-COP produced results equivalent to those of CHOP regarding
      efficacy and safety in aggressive NHL patients less than 70 years of age.
      CONCLUSIONS: Although both regimens effectively treated those patients with
      favorable prognostic factors, neither was satisfactory for treating those with
      poor prognostic factors.

PMID- 14648211
TI  - Halofantrine efficacy in non-immune children with imported acute Plasmodium
      falciparum malaria Infection.
AB  - A rising incidence of imported acute malaria has been observed in non-immune
      traveller children returning from the tropics to France. Halofantrine efficacy
      has been poorly assessed in non-immune children. In order to assess halofantrine
      efficacy in non-immune children with acute uncomplicated Plasmodium falciparum
      malaria, we collected data of children with positive blood smears in an open
      prospective study. Children with neurological manifestations, vomiting and
      congenital long QT were excluded. All children were hospitalised and received
      halofantrine (24 mg/kg divided into three doses per day) on an empty stomach.
      Persistent fever after day 3 defined failure. Relapse was defined by a positive
      blood smear with or without systemic symptoms within a 1 month follow-up period.
      In total, 52 children were enrolled. No failure was observed, but relapses
      occurred in 14/52. On univariate analysis, the mean age of children with relapse
      was significantly lower (P<0.05). Moreover, diarrhoea was more frequently
      associated with relapses (P<0.04). Age and diarrhoea were significant independent
      factors contributing to relapses. CONCLUSION: This study shows that with a
      relapse rate of 27%, this regimen with a 1-day course of halofantrine is not to
      be recommended.

PMID- 14648212
TI  - Arguments for early screening: a clinician's perspective.
AB  - Recent technological advances have led to an expansion in inborn errors that can
      be detected in the newborn period. Further developments in newborn screening will
      increase this number further. There are two main arguments put forward to support
      the developments of an expanded newborn screening programme. Firstly there may be
      an improvement in patient outcome. The early detection of disorders either in the
      pre-symptomatic or early symptomatic phase should, with treatment, result in the
      prevention of severe illness. This is evident for phenylketonuria and generally
      accepted for homocystinuria and medium-chain acyl-CoA dehydrogenase deficiency,
      disorders which have a long pre-symptomatic phase. However, other inborn errors
      may present within the first 10 days of life with severe illness, particularly
      neonatal encephalopathy. In order to effectively stop the rapid progression of
      these disorders, screening must be undertaken early although where severe
      metabolic decompensation occurs within 2 to 3 days of birth, newborn screening
      programmes are unlikely to be of direct benefit. Secondly an early diagnosis,
      even when this does not affect that individual's prognosis, may allow for
      accurate genetic advise to be given to the family and the opportunity to have
      prenatal diagnosis for future pregnancies. CONCLUSION: For the clinician, the
      introduction of an expanded and early newborn screening presents opportunities
      for improved patient and family care. However, it is important to be aware of
      possible detrimental effects on families of early screening. Screening tests must
      have adequate sensitivity and high specificity. Furthermore with early screening,
      close liaison between the laboratory, clinicians and community services is
      essential.

PMID- 14648213
TI  - Quality control requirements in neonatal screening.
AB  - One of the key tasks for the persons in charge of a neonatal screening laboratory
      is the control and maintenance of the quality of analytical results. The process
      of examining every day hundreds of blood spot samples obtained from newborn
      babies in order to divide the population of neonates into a low risk group and a
      high risk group, presents several challenges with respect to organisation,
      analytical accuracy and precision and effectiveness in the recall and treatment
      procedures. Quality in neonatal screening is not determined solely by the
      analytical performance of the laboratory; all the steps of the neonatal screening
      "system" contribute to the overall quality and performance. CONCLUSIONS:
      Programmes for the monitoring of the quality of neonatal screening have to be
      multidisciplinary and not restricted to the laboratory alone; not only analytical
      performance, but also the procedures used throughout the programme have to be
      monitored.

PMID- 14648214
TI  - Spleen and liver size biometry.

PMID- 14648215
TI  - Dopamine infusion and hypothyroxinaemia in very low birth weight preterm infants.
AB  - The purpose of this study was to assess the relationship between transient
      hypothyroxinaemia of prematurity (THOP) in very low birth weight newborns and
      dopamine administration. A total of 172 newborns was enrolled in a prospective
      observational study and divided into three groups: group A included newborns who
      were never treated with dopamine; group B were infants in whom dopamine treatment
      was discontinued for at least 6 h before the congenital hypothyroidism screening
      and group C included infants who were given dopamine during the screening. Among
      those newborns given dopamine, the THOP incidence was higher (11.6% in group A;
      53.8% in group B; 89.3% in group C), and the vales of TSH (1.67+/-2.32 microU/ml
      in group A; 1.29+/-1.74 microU/ml in group B; 0.89+/-1.34 microU/ml in group C)
      and thyroxine (6.1+/-2.2 microg/dl in group A; 3.9+/-1.9 microg/dl in group B;
      2.4+/-1.4 microg/dl in group C) were significantly lower. These differences were
      further confirmed even after gestational age stratification and mathematical
      correction for differences in clinical conditions. The effects of dopamine appear
      to be dose-dependent. CONCLUSION: Even if it cannot be excluded that reduced
      thyroid stimulating hormone and thyroxine concentrations are caused by non
      thyroidal illness, the results suggest that the infusion of dopamine reduces the
      thyroid stimulating hormone and thyroxine levels in very low birth weight
      newborns.

PMID- 14648216
TI  - Twenty years experience in rapid identification of congenital adrenal hyperplasia
      in Hungary.
AB  - The aim of this study was to assess the effectivity of the identification of
      patients with congenital adrenal hyperplasia (CAH) in Hungary in the absence of
      systematic neonatal screening and to estimate the incidence. Dried blood-spot
      samples of patients clinically suspected at any age to have CAH were collected
      between 1978 and 1998 throughout the whole country. 17-Hydroxyprogesterone (17
      OHP) was measured by radioimmunoassay. Age-specific cut-offs were used. The
      effectivity of the system was retrospectively assessed. Additional cases were
      sought to assess the overall incidence of CAH in Hungary. Among the 1,837
      patients investigated, 185 cases of CAH were identified. The overall effectivity
      was 94.7%. The sensitivity and the specificity were 98.9% and 94.2%,
      respectively. Salt-wasting (SW) boys were, on average, diagnosed 2 weeks later
      than SW girls, while both boys and girls with the simple virilising (SV) form
      were diagnosed at similar ages (2 versus 2.5 years). An additional 19 cases were
      diagnosed during the study period using other methods (plasma and urinary steroid
      profiles without blood-spot 17-OHP measurements). The incidence of classical CAH
      in Hungary was 1:14,300 (CI 95% between 1:12,450 and 1:16,795). Presuming that
      the incidence of CAH is the same among boys and girls, one can calculate that the
      diagnosis was missed in 24 boys (2 SW, 22 SV). CONCLUSION: it is possible to
      identify the vast majority of classical cases of congenital adrenal hyperplasia
      without a neonatal mass screening programme. However, a significant number of
      boys with the simple virilising form missed whereas both salt-wasting boys and
      girls are diagnosed safely.

PMID- 14648217
TI  - Further delineation of the congenital form of X-linked dyskeratosis congenita
      (Hoyeraal-Hreidarsson syndrome).
AB  - Hoyeraal-Hreidarsson syndrome represents a severe variant of dyskeratosis
      congenita (Zinsser-Cole-Engman syndrome). This X-linked recessive, progressive,
      multisystemic disorder reported so far in 12 pedigrees is characterised by
      intrauterine growth retardation, microcephaly, cerebellar hypoplasia, mental
      retardation, progressive combined immune deficiency and aplastic anaemia.
      Mutations in the DKC1gene on Xq28 have been identified in the X-linked form of
      dyskeratosis congenita and in some Hoyeraal-Hreidarsson syndrome patients. We
      report on two sibs and two other unrelated patients with the striking clinical
      features of Hoyeraal-Hreidarsson syndrome. Noticeably, all four had early
      digestive problems, with chronic, bloody diarrhoea and feeding problems causing
      one of the most difficult problems in the supportive treatment of this uniformly
      lethal condition. Pathological changes in the proliferative compartment of the
      digestive mucosa included alterations of the glandular architecture and focal
      rarefaction of the glands. This aspect seems consistent with altered telomerase
      function associated with a dyskerin mutation which may decrease the proliferative
      capacity of digestive epithelial cells. A missense mutation 146 C-->T (Thr49Met)
      in the DKC1gene was found in two unrelated patients, whereas mutation screening
      was negative for one single case. The absence of mutations of the DKC1gene in
      patients with Hoyeraal-Hreidarsson syndrome emphasises the probable implication
      of one or more other loci.

PMID- 14648218
TI  - Acute rheumatic fever without early carditis: an atypical clinical presentation.
AB  - The original Jones criteria, first introduced in 1944, have been modified four
      times and updated-revised criteria were published in 1992. A variety of clinical
      manifestations, which may be the presenting signs and symptoms of acute rheumatic
      fever, are not included in the updated-revised Jones criteria. A retrospective
      study was conducted on all children previously diagnosed to have acute rheumatic
      fever between September 1998 and September 2002. Review was focused on clinical
      presentation; out of 60 medical records reviewed, 4 patients with unusual
      clinical presentation were recognised and are reported here to highlight the
      potential diagnostic problems of acute rheumatic fever. They presented with
      atypical articular involvement, silent carditis and low-grade fever in the
      presence some time of a positive family history for rheumatic fever. CONCLUSION:
      a high index of suspicion and an awareness of the absence of early carditis are
      necessary to make the diagnosis of acute rheumatic fever.

PMID- 14648219
TI  - Loss of beta1-integrin-deficient cells during the development of endoderm-derived
      epithelia.
AB  - Beta1-integrins (beta1) represent cell surface receptors which mediate cell
      matrix and cell-cell interactions. Fassler and Meyer described chimeric mice
      containing transgenic cells that express the LacZ gene instead of the beta1 gene.
      They observed beta1-negative cells in all germ layers at embryonic day E 8.5.
      Later in development, using a glucose phosphate isomerase assay of homogenized
      tissue samples, high levels of transgenic cells were found in skeletal muscle and
      gut, low levels in lung, heart, and kidney and none in the liver and spleen
      (Fassler and Meyer 1995). In order to study which cell types require beta1 during
      development of the primitive gut including its derivatives, chimeric fetuses
      containing 15 to 25% transgenic cells were obtained at days E 14.5 and E 15.5.
      They were LacZ (beta-galactosidase) stained "en bloc" and cross-sectioned head to
      tail. In esophagus, trachea, lung, stomach, hindgut, and the future urinary
      bladder, we observed various mesoderm-derived beta1-negative cells (e.g.
      fibroblasts, chondrocytes, endothelial cells, and smooth muscle cells) but no
      beta1-negative epithelial cells. Since the epithelia of lung, esophagus, trachea,
      stomach, hindgut, and urinary bladder are derived from the endodermal gut tube,
      we hypothesize that beta1 is essential for the development and/or survival of the
      epithelia of the fore- and hindgut and its derivatives.

PMID- 14648220
TI  - Ultrastructure of goblet-cell metaplasia from Clara cell in the allergic
      asthmatic airway inflammation in a mouse model of asthma in vivo.
AB  - Mucus overproduction from goblet cells, a characteristic feature of the allergic
      asthmatic inflammation induced by ovalbumin (OVA) in mice, was examined
      morphologically. In OVA-untreated (normal) mice, there were no goblet cells in
      intrapulmonary bronchus and bronchiole. However, goblet cells with or without
      hyperplasia in the mucosa of inflamed bronchus-bronchiole were recognized in the
      allergic asthmatic mice. The non-ciliated epithelium containing electron lucent
      granules (mucus) showed many similarities to Clara cells, which have
      characteristic secretory granules and many mitochondria, except for the less
      developed smooth endoplasmic reticulum seen in normal mice. Ciliated Clara cells
      with or without mucus were rarely recognized. In addition, mucus was found in
      neither ciliated nor basal epithelium. The present study suggests that goblet
      cell metaplasia in the bronchus and bronchiole of inflamed mucosa may be derived,
      at least in part, from Clara cells.

PMID- 14648221
TI  - Exocrine cell transdifferentiation in dexamethasone-treated rat pancreas.
AB  - Injured pancreatic tissue, for example, after duct ligation, undergoes
      remodeling, which involves the replacement of exocrine acini by duct-like
      structures. This acinoductal metaplasia is probably at least partly due to
      transdifferentiation of amylase-positive, cytokeratin-20 (CK20)-negative acinar
      cells into amylase-negative, CK20-positive duct-like cells. Due to the kinetics
      of these phenotypic changes, however, it has not been possible to demonstrate
      transitional stages of differentiation, which would express both markers at the
      same time. We took advantage of the fact that dexamethasone treatment inhibits
      the loss of amylase from acinar cells to demonstrate transitional cells co
      expressing amylase and CK20. This was found both in vivo, where duct-ligation
      induced metaplasia, and in vitro, after isolation of acini. In addition, we found
      evidence for an acinar-to-islet conversion under the form of transitional cells
      co-expressing amylase and insulin. These observations strengthen the notion that
      fully differentiated cells, such as exocrine pancreatic cells, retain the
      capacity to undergo important phenotypic switches. This finding could have
      applications in tissue engineering or cell replacement strategies.

PMID- 14648222
TI  - odd-skipped homologs function during gut development in C. elegans.
AB  - Genes in the odd-skipped (odd) family encode a discrete subset of C2H2 zinc
      finger proteins that are widely distributed among metazoan phyla. Although the
      initial member (odd) was identified as a Drosophila pair-rule gene, various
      homologs are expressed within each of the three germ layers in complex patterns
      that suggest roles in many pathways beyond segmentation. To further investigate
      the evolutionary history and extant functions of genes in this family, we have
      initiated a characterization of two homologs, odd-1 and odd-2, identified in the
      genome of the nematode, Caenorhabditis elegans. Sequence comparisons with
      homologs from insects (Drosophila and Anopheles) and mammals suggest that two
      paralogs were present within an ancestral metazoan; additional insect paralogs
      and both extant mammalian genes likely resulted from gene duplications that
      occurred after the split between the arthropods and chordates. Analyses of gene
      function using RNAi indicate that odd-1 and odd-2 play essential and distinct
      roles during gut development. Specific expression of both genes in the developing
      intestine and other cells in the vicinity of the gut was shown using GFP
      reporters. These results indicate primary functions for both genes that are most
      like those of the Drosophila paralogs bowel and drumstick, and support a model in
      which gut specification represents the ancestral role for genes in this family.

PMID- 14648223
TI  - Embryonic origins of the two main classes of hemocytes--granular cells and
      plasmatocytes--in Manduca sexta.
AB  - Cell-mediated responses of the moth immune system involve the interaction of two
      main classes of hemocytes-granular cells and plasmatocytes. During embryogenesis,
      granular cells arise much earlier than plasmatocytes, and the presence of
      granular cells is closely coupled with the formation of basal laminae that line
      the hemocoel occupied by hemocytes. Although epithelial cells contribute the
      large extracellular matrix protein lacunin to embryonic matrices before granular
      cells begin contributing this protein to basal laminae, the spatial pattern of
      lacunin expression in early embryos parallels the later distribution of granular
      cells over surfaces of basal laminae. Plasmatocytes arise late in embryogenesis,
      after the cessation of the major morphogenetic movements and the establishment of
      intact basal laminae. Granular cells are intimately involved with remodeling of
      basal laminae, and disruptions in the structure of basal laminae can trigger an
      autoimmune response of granular cells and plasmatocytes. By arising after basal
      laminae have been molded and remodeled by granular cells, plasmatocytes
      presumably do not encounter the cues that trigger their aggregation and an
      autoimmune response.

PMID- 14648224
TI  - Positive facial expressions are recognized faster than negative facial
      expressions, but why?
AB  - Three experiments examined the recognition speed advantage for happy faces. The
      results replicated earlier findings by showing that positive (happy) facial
      expressions were recognized faster than negative (disgusted or sad) facial
      expressions (Experiments 1 and 2). In addition, the results showed that this
      effect was evident even when low-level physical differences between positive and
      negative faces were controlled by using schematic faces (Experiment 2), and that
      the effect was not attributable to an artifact arising from facilitated
      recognition of a single feature in the happy faces (up-turned mouth line,
      Experiment 3). Together, these results suggest that the happy face advantage may
      reflect a higher-level asymmetry in the recognition and categorization of
      emotionally positive and negative signals.

PMID- 14648225
TI  - The ideomotor principle and motor sequence acquisition: tone effects facilitate
      movement chunking.
AB  - Participants practiced short sequences of key presses; sequence length and
      response-effect mapping were the independent variables. Contingent, distinct key
      effect relations were contrasted with either contingent but uniform or no
      response effects. In Experiment 1, tone effects were relevant as response
      specific stimuli and also as effects. The sequence length effect for the tones
      group was reduced. In Experiment 2, participants were informed about the
      sequences to be executed and then given varying amounts of preparation time
      before the start signal. A reduction in the sequence length effect was observed,
      and initiation times and mean interresponse time (IRTs) were generally reduced in
      the tone group. Preparation time could compensate for some but not all of the
      latency reducing influence of the tone effects. The results are discussed with
      reference to ideomotor approaches to motor control, i.e., the notion that actions
      are represented in sensory format.

PMID- 14648227
TI  - Antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) was reported in the early 1980s as the
      association of thrombosis, recurrent pregnancy loss in the presence of
      anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). Since then,
      many other clinical manifestations have been associated with aPL. Almost any
      organ and tissue may be involved in the disease, including the brain, the heart,
      the kidneys, the placenta and many more. aPL are a heterogeneous group of
      autoantibodies that are detected by immunoassays and functional coagulation
      tests. The antigenic targets are negatively charged phospholipids and serum
      phospholipid-binding proteins. Despite the strong association between aPL and
      thrombosis, the pathogenic role of aPL in the development of thrombosis has not
      been fully elucidated. Proposed mechanisms include antibody-mediated interference
      with coagulation homeostasis, activation of platelets and endothelial cells and a
      T-cell immune response to serum phospholipid-binding proteins. The mainstay of
      therapy is anticoagulation, whereas immunosuppression seems to be ineffective.
      Recommendations for the management of thrombosis in the antiphospholipid antibody
      syndrome have been based largely on retrospective case series. Several
      prospective clinical trials are currently underway and their results will
      probably lead to a more precise therapeutic approach of this problem.

PMID- 14648226
TI  - Characterisation of early transcriptional changes involving multiple signalling
      pathways in the Mla13 barley interaction with powdery mildew ( Blumeria graminis
      f. sp. hordei).
AB  - Suppression subtractive hybridisation was used to isolate 21 cDNAs ( bmi1- bmi21)
      up-regulated 1-5 h post-inoculation (hpi) in a barley ( Hordeum vulgare L. cv.
      Pallas) near-isogenic line (NIL) P11 ( Mla13) challenged with either avirulent or
      virulent isolates of Blumeria graminis f. sp. hordei. Transcriptional changes at
      these time-points are crucial for the Mla-mediated hypersensitive response [W.R.
      Bushnell and Z. Liu (1994) Physiol Mol Plant Pathol 44:389-402]. Seven sequences
      were up-regulated by 1 hpi, when the pathogen has formed only the primary germ
      tube. Some transcripts were similar to genes with a role in regulating programmed
      cell death in animals, including NF kappaB and oxysterol-binding protein.
      Moreover, bmi7, similar to rice resistance gene Xa21, was rapidly up-regulated in
      both compatible and incompatible interactions, but was then down-regulated by 5
      hpi in the virulent interaction. Only nine of the transcripts were up-regulated
      in mlo5 resistance in cv. Pallas NIL P22, confirming differential pathway
      induction between Mla13 and mlo5. However, eight sequences up-regulated in the
      Mla13 response in P11 were already highly elevated in uninoculated mlo5 mutant
      P22, suggesting that they may be negatively regulated by wild-type Mlo.
      Regulation of bmi sequences was investigated using salicylic acid, methyl
      jasmonate, ethylene, H(2)O(2), abscisic acid, wounding and a glucan elicitor. No
      single stimulus up-regulated all genes, suggesting either combinations of these
      stimuli, or additional stimuli, are involved in early Mla13 and mlo5 resistances.
      Whereas H(2)O(2) up- or down-regulated 17 of the transcripts detected in Northern
      analyses, salicylic acid stimulated only down-regulation of 5 transcripts.

PMID- 14648228
TI  - Biology of human bone marrow stem cells.
AB  - The bone marrow is constituted of two separate and distinct stem cells. The
      hematopoietic stem cells (HSC) are responsible for the production and maintenance
      of all the mature blood cells. The mesenchymal stem cells constituted the bone
      marrow stroma. In this report we review our current understanding on both stem
      cell populations. We also discuss the recent unexpected degree of differentiation
      plasticity that have been reported recently and the impacts these new discoveries
      may have in stem cell therapy.

PMID- 14648229
TI  - Cytosine deaminase versus thymidine kinase: a comparison of the antitumor
      activity.
AB  - The efficacy of single and combination suicide gene therapy was evaluated using a
      Herpes simplex virus thymidine kinase/ganciclovir system and Escherichia coli
      cytosine deaminase/5-fluorocytosine system on the rat prostate tumor cell line
      R3327 AT-1. The wild-type R3327 AT-1 cell line was transfected with a
      bifunctional fusion gene CDglyTK, which had the advantage that the resulting
      R3327 AT-1/CDglyTK cell line has the same amount of cytosine deaminase and
      thymidine kinase molecules. The percentage of viable R3327 AT-1/CDglyTK cells
      after 96 h incubation with 0.1 micro g/ml ganciclovir or 10 micro g/ml 5
      fluorocytosine were 85% and 52% of controls, respectively. The cell viability
      when both suicide genes systems were activated was 43%. For in vivo analysis,
      Copenhagen rats were injected subcutaneously with R3327 AT-1 or R3327 AT
      1/CDglyTK cells and treated with 30 mg/kg ganciclovir, 500 mg/kg 5
      fluorocytosine, or both prodrugs together. A survival of 83% with the thymidine
      kinase/ganciclovir and 57% with the CD/5-FC could be observed. Only co
      administration of thymidine kinase- and cytosine deaminase-specific prodrugs
      resulted in a 100% recurrence-free survival of the Copenhagen rats with a Dunning
      R3327 AT-1/CDglyTK prostate tumor and showed an additive cytotoxic effect.
      Calculation of the degree of activation and the potential of activation can be
      used to predict the success of a suicide gene therapy. In our case, the cytosine
      deaminase/5-fluorocytosine system had a low degree of activation (value 40),
      which is also found in the low response to 5- fluorocytosine in vivo (57% tumor
      free).

PMID- 14648230
TI  - Anti-cytomegalovirus (CMV) IgG antibody titer in patients with risk factors to
      atherosclerosis.
AB  - Studies have demonstrated cytomegalovirus (CMV) DNA particles in restenotic
      lesions in atherosclerotic coronary arteries. We have shown that high (>1:800)
      anti-CMV IgG antibody titers in the serum are associated with active coronary
      disease and with post coronary angioplasty restenosis. In this study we assessed
      the anti-CMV antibody titer in patients with risk factors for atherosclerosis
      (but without documented clinical manifestations). One hundred and eighly-seven
      patients (men and women aged 40-80 years) that were admitted to the Department of
      Internal Medicine were recruited to this prospective study. All had at least one
      risk factor for atherosclerosis, and none had documented coronary artery disease.
      Fasting blood samples were drawn on admission. Risk factors included
      hypertension, diabetes mellitus, active smoking, hyperlipidemia, and a positive
      family history. Ninety-three age- and sex-matched individuals without
      atherosclerosis risk factors served as the control group. One Hundred and
      twentysix patients had high anti-CMV antibody titers (>/=1:800) compared with
      none in the control group. Although 80 patients (90%) in the control group were
      seropositive, none had anti-CMV IgG antibody titers higher than 1:400. The
      statistical difference between the patients and the control group was highly
      significant ( p<0.0001). An immunological response against CMV (expressed as an
      anti-CMV IgG antibody titer) could be a marker of a long-standing immunological
      reaction causing an inflammatory response that eventually would cause advanced
      clinical atherosclerosis. We suggest that anti-CMV antibody titer should be used
      as an early predictor of atherosclerosis. Our findings support the infectious
      theory and an association between CMV infection and atherosclerosis at an early
      stage, maybe even years before clinical events occur.

PMID- 14648231
TI  - The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor
      gene is not associated with acute myocardial infarction.
AB  - CD surface molecules mediates cell activation and signaling. In particular, CD14
      on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide.
      Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis.
      It has been recently shown that a C(-260)T polymorphism in the promoter of the
      CD14 receptor may be a risk factor for coronary artery disease. Recently this
      association has been questioned because no increased risk was found with the T
      allele, even in the homozygous state. In the present study we investigated a
      possible association between the C(-260)T polymorphism in the CD14 promoter and
      acute myocardial infarction. Two hundred and thrteen patients with and acute
      myocardial infarction 213 healthy controls were included in the study. Genotype
      frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by
      polimerase chain reaction and the amplified product was cleaved with HaeIII. The
      frequency of the T allele was not significantly different in patients compared
      with controls. In this study we were not able to detect differences of frequency
      of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of
      myocardial infarction and controls.

PMID- 14648232
TI  - Helicobacter pylori and cagA and vacA gene status in children from Brazil with
      chronic gastritis.
AB  - Helicobacter pylori has been shown to be strongly associated with chronic
      gastritis, gastric and duodenal ulceration, and is a risk factor for gastric
      carcinoma. Histology, urease, culture, and polymerase chain reaction have been
      employed as for H. pylori diagnostic methods, pre and post treatment or during
      follow-up of dyspeptic adult individuals referred for endoscopy. In order to
      obtain a more-sensitive and specific method for H. pylori detection, we evaluated
      gastric body and antrum biopsies of 134 consecutive Brazilian consecutive
      dyspeptic children aged 1-16 years by rapid urease test, histology and polymerase
      chain reaction using two pairs of oligonucleotides. Our results indicated that
      polymerase chain reaction with Southern blotting and hybridization with specific
      chemiluminescent probes increased the number of positive H. pylori patients by
      35%. The genotyping of H. pylori strains directly from gastric biopsy using the
      same nucleic acid methodology revealed that there is no association of chronic
      gastritis in our infant patients with vacA s1 and the presence of the cagA gene.
      These data suggest an initial infection of children with normal mucosa and
      probably others factors than vacA s1 genotype or the presence of the cagA gene
      are associated with the onset of gastric disease. Altogether, our results
      reinforce the need for using more sensitive diagnostic methods in order to
      understand the role of H. pylori in the genesis of gastric disease in children
      and its progression in adults.

PMID- 14648233
TI  - Optimized polymerase chain reaction-based single-strand conformation polymorphism
      analysis of p53 gene applied to Bulgarian patients with invasive breast cancer.
AB  - During the last few decades a substantial amount of evidence has accumulated
      proving that the abrogation of the normal p53 pathway is a critical step in the
      initiation and progression of tumors. Decoding the genetic mechanisms involved in
      carcinogenesis requires screening for consistent genetic tumor alterations,
      including those concerning the p53 gene. Thus, practical, efficient, and
      inexpensive techniques for accurate determination of p53 mutational status are
      needed. Polymerase chain reaction/single-strand conformation polymorphism (PCR
      SSCP) analysis is considered to be a useful tool to investigate the role of the
      p53 gene in the development and progression of human cancers. The sensitivity of
      the method can be increased considerably by varying the experimental conditions.
      Here we demonstrate a scheme of PCR-SSCP optimization for detection of p53 gene
      mutations of patients with various cancers. Optimal conditions for PCRSSCP of p53
      exons 4-9 are reported. Such PCR-SSCP optimization could allow an increase in the
      sensitivity and reproducibility of the technique and facilitates screening of
      large series of patients to assess the clinical significance of p53 mutations in
      human cancers. Using the optimized PCR-SSCP analysis we screened Bulgarian
      patients with invasive breast cancer for p53 gene mutations and registered a
      33.33% frequency of mutations. To date, there are no data concerning the p53
      status of Bulgarian breast cancer patients. Screening for p53 gene mutations
      enables an accurate and routine determination of the p53 status of patients with
      cancer and may be applied in clinical oncology to cancer diagnosis, prediction of
      prognosis and response to treatment.

PMID- 14648234
TI  - Dysregulation of blood lymphocyte subsets and natural killer cells in
      schistosomal liver cirrhosis and hepatocellular carcinoma.
AB  - Immunological factors are important in the pathogenesis of a wide spectrum of
      hepatobiliary diseases. Using flow cytometry, we determined the changes in
      lymphocyte subsets and natural killer cells in 123 individuals (81 patients with
      liver disease and 42 healthy volunteers). The liver diseases included periportal
      fibrosis (PPF, 10 patients), liver cirrhosis (LC, 31 patients), and
      hepatocellular carcinoma (HCC, 40 patients). Schistosomiasis and viral hepatitis
      B and C were the putative etiological agents of liver diseases. Immunophenotyping
      by indirect immunofluorescence was conducted using monoclonal antibodies to CD3
      (T-lymphocytes), CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T
      cells), and CD57 (natural killer cells) cell surface markers. Immunophenotyping
      of PPF patients showed no significant changes in all markers compared with the
      healthy controls. However, there was a significant decrease ( P<0.01) in CD3 and
      CD4 T-cells, and a highly significant increase ( P<0.001) in CD57 T-cells in
      patients with LC or HCC. In addition, LC and HCC patients showed no significant
      change in CD8 T-cells compared with controls. In conclusion, the progression of
      liver diseases is associated with a dysregulation of cellular immune responses. T
      lymphocytes and natural killer cells may play a role in the immunopathogenesis of
      liver cirrhosis and HCC.

PMID- 14648236
TI  - Utility of monaural spectral cues is enhanced in the presence of cues to sound
      source lateral angle.
AB  - The contention that normally binaural listeners can localize sound under monaural
      conditions has been challenged by Wightman and Kistler (J. Acoust. Soc. Am.
      101:1050-1063, 1997), who found that listeners are almost completely unable to
      localize virtual sources of sound when sound is presented to only one ear.
      Wightman and Kistler's results raise the question of whether monaural spectral
      cues are used by listeners to localize sound under binaural conditions. We have
      examined the possibility that monaural spectral cues provide useful information
      regarding sound-source elevation and front-back hemifield when interaural time
      differences are available to specify sound-source lateral angle. The accuracy
      with which elevation and front-back hemifield could be determined was compared
      between a monaural condition and a binaural condition in which a wide-band signal
      was presented to the near ear and a version of the signal that had been lowpass
      filtered at 2.5 kHz was presented to the far ear. It was found that accuracy was
      substantially greater in the latter condition, suggesting that information
      regarding sound-source lateral angle is required for monaural spectral cues to
      elevation and front-back hemifield to be correctly interpreted.

PMID- 14648237
TI  - Progressive hearing loss and increased susceptibility to noise-induced hearing
      loss in mice carrying a Cdh23 but not a Myo7a mutation.
AB  - Exposure to intense noise can damage the stereocilia of sensory hair cells in the
      inner ear. Since stereocilia play a vital role in the transduction of sound from
      a mechanical stimulus into an electrical one, this pathology is thought to
      contribute to noise-induced hearing loss. Mice homozygous for null mutations in
      either the myosin VIIa ( Myo7a) or cadherin 23 ( Cdh23) genes are deaf and have
      disorganized stereocilia bundles. We show that mice heterozygous for a presumed
      null allele of Cdh23 ( Cdh23(v)) have low- and high-frequency hearing loss at 5-6
      weeks of age, the high-frequency component of which worsens with increasing age.
      We also show that noise-induced hearing loss in 11-12-week-old Cdh23(v)
      heterozygotes is two times greater than for wild-type littermates. Interestingly,
      these effects are dependent upon the genetic background on which the Cdh23(v)
      mutation is carried. Noise-induced hearing loss in 11-12-week-old mice
      heterozygous for a null allele of Myo7a ( Myo7a(4626SB)) is not significantly
      different from wild-type littermates. CDH23 is the first gene known to cause
      deafness in the human population to be linked with predisposition to noise
      induced hearing loss.

PMID- 14648238
TI  - The auxin-induced transcriptome for etiolated Arabidopsis seedlings using a
      structure/function approach.
AB  - To increase our understanding of the mode of action of auxin, we analyzed auxin
      induced changes in the Arabidopsis transcriptome with microarrays representing
      20426 Arabidopsis genes. Treatment of etiolated seedlings with low concentrations
      of the auxin, indole-3-acetic acid (IAA), decreased the expression levels of 23
      genes, whereas it increased the expression levels of 47 genes within 20 min.
      After 40 min, the directional trend in genomic change was predominantly an
      increase in gene expression. Among the most rapidly induced changes are those in
      genes encoding transcription factors. Promoter regions of transiently induced
      genes contained DNA motifs that bind auxin response (ARFAT) and silence element
      binding factors whereas genes induced by IAA during the entire experimental
      period contained MYC and ARFAT DNA motifs at higher frequencies. Six structurally
      diverse auxins were analyzed to determine genes that are unique to a specific
      auxin, as well as a common set of genes that are rapidly regulated by all tested
      auxins, thus enabling the identification of shared DNA motifs. In addition to
      ARFAT, analysis of promoter regions of genes induced by all six auxins revealed
      the presence of an abscisic-acid-responsive DC3 promoter-binding factor and low
      temperature responsive elements suggesting a possible role for abscisic acid in
      modulating auxin-induced responses.

PMID- 14648239
TI  - Genes associated with the end of dormancy in grapes.
AB  - A grape bud EST library was constructed and 4270 ESTs sequenced. The library
      clones were arrayed for the purpose of investigating the level of gene expression
      over time, particularly leading up to the buds' release from dormancy. The arrays
      were hybridized with P(33)-labeled probes produced from samples of buds collected
      at weekly intervals. These probes covered the time from 9 weeks prior to bud
      burst until just after the emergence of the shoots. Expression patterns from
      these genes have been examined. It was found that 74% of the genes in the data
      set were homologous to known proteins. Genes were then assigned to functional
      categories according to their primary BLAST match. Of these 13% were involved
      with photosynthesis, 13% with disease resistance and defense, 5% energy, 12%
      metabolism, 20% protein production and processing, 25% cell structure and plant
      growth and the remaining 12% were unclassified The expression pattern of a
      selection of "candidate" genes retrieved from literature previously reporting an
      association with dormancy changes was assessed. On closer examination most of
      these genes relate to the oxidative processes and stress responses within the
      cell. The results of this study show that even in the dormant state, gene
      expression in the buds is high.

PMID- 14648242
TI  - Specific mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease
      carriers: dating of founder ancestor.
AB  - The incidence of Tay-Sachs disease (TSD) carriers, as defined by enzyme assay, is
      1:29 among Ashkenazi Jews and 1:110 among Moroccan Jews. An elevated carrier
      frequency of 1:140 was also observed in the Iraqi Jews (IJ), while in other
      Israeli populations the world's pan-ethnic frequency of approximately 1:280 has
      been found. Recently a novel mutation, G749T, has been reported in 38.7% of the
      IJ carriers (24/62). Here we report a second novel HEXA mutation specific to the
      IJ TDS carriers: a substitution of cytosine 1351 by guanosine (C1351G), resulting
      in the change of leucine to valine in position 451. This mutation was found in
      33.9% (21/62) of the carriers and in none of 100 non-carrier IJ. In addition to
      the two specific mutations, 14.5% (9/62) of the IJ carriers bear a known "Jewish"
      mutation (Ashkenazi or Moroccan) and 11.3% (7/62) carry a known "non-Jewish"
      mutation. In 1 DNA sample no mutation has yet been detected. To investigate the
      genetic history of the IJ-specific mutations (C1351G and G749T), the allelic
      distribution of four polymorphic markers (D15S131, D15S1025, D15S981, D15S1050)
      was analyzed in IJ heterozygotes and ethnically matched controls. Based on
      linkage disequilibrium, recombination factor (theta) between the markers and
      mutated loci, and the population growth correction, we deduced that G749T
      occurred in a founder ancestor 44.8 +/- 14.2 generations (g) ago [95% confidence
      interval (CI) 17.0-72.6 g] and C1351G arose 80.4 +/- 35.9 g ago (95% CI 44.5
      116.3 g). Thus, the estimated dates for introduction of mutations are: 626 +/-
      426 A.D. (200-1052 A.D.) for G749T and 442 +/- 1077 B.C. (1519 B.C. to 635 A.D.)
      for C1351G.

PMID- 14648243
TI  - The Shouldice herniorrhaphy in the treatment of inguinal hernias: a prospective
      study on 775 patients.
AB  - The authors present a study of 775 patients who underwent a Shouldice
      herniorrhaphy between 1987 and 2000, as performed by one surgeon. Average patient
      age was 52 years, and 93% of patients were male. Local anesthesia with sedation
      was used in 643 cases (83%) and regional anesthesia in 13%. The length of the
      incision was 9.5 cm. The average duration of surgery was 57.5 min (40-75).
      Tolerance to local anesthesia with sedation was 93%, a similar percentage to that
      of general anesthesia. The most significant postoperative complications were:
      urinary retention 8%, headache 7%, and ecchymosis 6%. Hospitalization time in 76%
      of the cases was 1 day, while 20% of interventions were undertaken on an
      outpatient basis. The average absence from work was 20 days. The recurrence rate
      at 7 years was 2%.

PMID- 14648244
TI  - Early results of a single-blinded, randomized, controlled, Internet-based
      multicenter trial comparing Prolene and Vypro II mesh in Lichtenstein
      hernioplasty.
AB  - BACKGROUND: The standard polypropylene mesh used in Lichtenstein's operation
      induces a strong foreign-tissue reaction with potentially harmful effects. A mesh
      with less polypropylene could possibly be beneficial. PATIENTS AND METHODS: Six
      hundred men with inguinal hernias were randomized to Lichtenstein's operation
      with Prolene or Vypro II in a single-blinded multicenter trial. The randomization
      was performed by a computer algorithm in a database through the Internet. All
      data were entered and directly validated in the database through the Internet.
      RESULTS: The meshes had comparable results in return to work, return to daily
      activities, complications, postoperative pain, and quality of life during the
      first 8 weeks of rehabilitation. CONCLUSIONS: Lichtenstein's operation with
      either Prolene or Vypro II is safe and well tolerated with an acceptable
      postoperative rehabilitation time and a high quality of life 2 months after
      surgery. The study was facilitated by the use of a database through the Internet.

PMID- 14648246
TI  - [Experimental and clinical study of the stability of an osteosynthesis plate for
      the atrophic mandible].
AB  - BACKGROUND: The high rate of complications led us to develop a new osteosynthesis
      plate for the treatment of the fractured atrophied mandible. The development of
      the new so-called pencil-bone plate is based on the 2.0 mini-plate system
      manufactured by the Medartis Company. MATERIAL AND METHODS: Finite elements (FE)
      analysis of the new plate as well as flexibility experiments were undertaken, and
      14 patients with 16 fractures of the atrophied mandible were treated with the
      pencil-bone plate between October 2000 and November 2001. RESULTS: The results
      clearly show that the pencil-bone plate reacted in both the FE model and the
      static flexibility experiment in a more stable way than a standard 2.0 plate. In
      13 patients, healing proceeded without serious complications; all of the patients
      showed subjective, nearly unchanged chewing, speaking, and swallowing abilities
      and no complications occurred when wearing dentures. One patient underwent
      surgical intervention after a new trauma. CONCLUSION: The clinical outcome of the
      treated fractures confirmed the experimental results, which proved the high
      stability of the plate in the area of the fracture site. Due to the mini-plate
      format the intraoral application of the plate is possible without problems. The
      intraoral access allows rapid operation followed by a minimum of morbidity. A
      great advantage of the small dimension system is the unrestricted wearing of
      dentures after the application.

PMID- 14648247
TI  - [Joint loose bodies in the mandible. Diagnostic criteria and pathways for therapy
      planning].
AB  - Osteochondrosis dissecans (OD) and synovial chondromatosis (SC) are two rare
      causes for loose bodies in the temporomandibular joint. It is assumed that OD is
      a reaction of some type of joint trauma. Gene mutations similar to what is known
      in chondrosarcomas can be found in metaplastic SC. The reasons for mutations are
      still unknown. Both diseases have very similar symptoms. Patients suffer from
      preauricular swelling, facial or temporomandibular joint pain, and occasional
      joint locking. In addition, radiological imaging (MRI) is difficult in evaluating
      the differential diagnosis of presented intra- or periarticular pathology. To
      overcome diagnostic problems, we strongly support temporomandibular joint
      arthroscopy as a diagnostic and therapeutic tool. The decision whether or not
      total synovectomy is needed or if simple removal of fragments is adequate can be
      evaluated in vivo including the option of histopathological examination.

PMID- 14648248
TI  - [Odontogenic foci--possible etiology of urticaria?].
AB  - Recent studies have shown that chronic odontogenic infections could pose a risk
      for myocardial infarction, cerebral ischemia, and arteriosclerosis. However, the
      correlation between urticaria and dental infections has rarely been examined so
      far. Therefore, we performed a case-control study using a standardized
      questionnaire and examination. We investigated 66 patients suffering from an
      acute or chronic urticaria and 65 age- and sex-matched healthy patients as a
      control group. Dental status was determined by a so-called total dental index
      (TDI) which primarily reflects caries, periodontitis, periapical lesions, and
      nonvital and missing teeth. All 66 patients were referred from the department of
      dermatology. After their treatment in hospital, all patients received a
      questionnaire with questions on intensity and localization of the urticaria. The
      TDI of the urticaria patients was slightly better ( n=66; 2.6+/-1.98) than that
      of the control group ( n=65, TDI=3.3+/-1.86). Subsequently, it was determined if
      the urticaria had receded after dental treatment. In conclusion, chronic dental
      infections do not seem to correlate with an increased risk for urticaria.

PMID- 14648249
TI  - [Facial clefts and their coding with LAHS nomenclature].
AB  - Research and treatment of clefts of lip, alveolus, and palate requires exact,
      reliable and reproducible terminology and documentation. In this paper we suggest
      a simple system to record a detailed diagnosis for every case of cleft. All
      anatomical regions involved by the cleft are considered and the extent in these
      regions is described. This nomenclature has been proposed for usage by the
      Interdisciplinary Cleft Palate and Craniofacial Anomalies Committee of the German
      Associations for Cranio-Maxillofacial Surgery, Orthodontics, Phoniatrics,
      Pedaudiology and ENT.

PMID- 14648250
TI  - [Bimaxillary osteotomy with and without condylar positioning--a 1981-2002 long
      term study].
AB  - PURPOSE: The introduction of the four-splint technique in our hospital in 1997
      made possible the reproducible centric condyle positioning in bimaxillary
      osteotomies, while taking the auto rotation of the mandible into consideration
      and avoiding steps in the mandibular osteotomy line. PATIENTS AND METHODS: From
      1981 to 2002 a total of 622 patients underwent bimaxillary osteotomy surgery.
      During 1981-1997 a total of 395 patients (63.5%) underwent surgery without or
      only with centric condyle positioning in sagittal ramus osteotomy of the
      mandible. During 1997-2002 a total of 227 patients (36.5%) underwent surgery with
      continuous centric condyle positioning with the four-splint technique. RESULTS:
      In patients with preoperative functional disorders, surgery with continuous
      centric condyle positioning resulted in statistically significant (p<0.05)
      improvement compared to those who underwent surgery without continuous centric
      condyle positioning. CONCLUSION: The results confirm the indication for
      continuous centric condyle positioning in bimaxillary osteotomies.

PMID- 14648251
TI  - [Primary implant stability with different bone surgery techniques. An in vitro
      study of the mandible of the minipig].
AB  - The treatment concept of osseointegration is based on a stable embodiment of
      implants in bone and the maintenance of stability during functional load. A goal
      of the surgical preparation technique is therefore to obtain a stable and firm
      implant anchorage. The aim of this study was to evaluate implant stability after
      different surgical treatment of the bony implantation bed. Thirty cylindrical
      solid-screw-shaped implants with standard SLA ITI configuration were implanted
      into the explanted mandibles of five minipigs. The implant sites were prepared
      either by a conventional burr technique (group A), by burr technique with
      additional thread cutting (group B), or by the osteotome technique (group C).
      Primary implant stability was evaluated by resonance frequency analysis and
      removal torque test. The average value of the resonance frequency analysis (RFA)
      was 6000+/-469 cycles/s in group A, 5700+/-557 cycles/s in group B, and 5540+/
      527 cycles/s in group C. Removal torque values of group A (507+/-57 Nmm) were
      significantly higher than those of group B (466+/-45 Nmm) and group C (240+/-31
      Nmm) (between group A and C p<0.05, group A to B p=0.39, and B to C p<0.05). It
      can be concluded from this study that the conventional burr technique achieves a
      statistically significantly better primary bone anchorage than the osteotome
      technique.

PMID- 14648252
TI  - [Temporomandibular function after malocclusion operations compared with a
      representative population group study].
AB  - AIM: The temporomandibular function of patients after orthognathic surgery was
      evaluated with the Helkimo index (D 0-III) and compared with a normal population.
      PATIENTS AND METHODS: Temporomandibular disorders (TMD) were evaluated with the
      Helkimo index (D 0-III) in a group of patients (n=105, F=69, M=36) after
      osteotomies. The average follow-up time was 47 months (9-141 months). The
      osteotomies performed were as follows: 58 bilateral sagittal split osteotomies,
      12 Le Fort I osteotomies, 22 bimaxillary osteotomies, and 13 segment-osteotomies.
      A control group (n=202, F=114, M=88, age 20-39 years) was examined in an
      epidemiological study. The statistical analysis was performed using Windows
      software SPSS 10.0. RESULT: In 82.8% of the patients no symptoms or mild
      dysfunction were found. The comparison between the patient group (31.4%) and the
      control group (31.7%) revealed a similar frequency. The most frequent dysfunction
      was a reduced mobility of the mandible, which determined the statistical
      significance (p<0,05) between the patients and the control group for the
      dysfunction group D II and D III. The chi-square test could not detect any
      difference between sex and the kind of osteotomy with regard to dysfunction.

PMID- 14648253
TI  - [Quantitative determination of CMV-DNA in saliva of patients with bone marrow and
      stem cell transplantation using TaqMan-PCR].
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection is associated with severe and
      life-threatening diseases in immunocompromised patients, especially after bone
      marrow (BM) and stem cell (SC) transplantation. Prior to transplantation the
      potential risk of HCMV disease is therefore determined by HCMV-antibody blood
      testing of transplant donor (D) and recipient (R). Virus carriers are positive
      for anti-CMV-IgG. Virus patterns are distinguished as follows: group 1 (D+/R+),
      group 2 (D-/R+), group 3 (D+/R-), and group 4 (D-/R-). AIM: The aim of this study
      was qualitative and quantitative determination of the HCMV DNA load in saliva of
      BM and SC transplantation patients. PATIENTS AND METHOD: Unstimulated saliva was
      collected from 20 patients prior to BM and SC transplantation, during the time of
      conditioning, and after transplantation. DNA was isolated and analyzed for
      evidence of HCMV DNA with TaqMan PCR. RESULTS: HCMV DNA was isolated in seven
      cases. In all group 1 patients (D+/R+) HCMV DNA could be demonstrated. Only three
      of seven group 2 patients (D-/R+) were positive for HCMV DNA. The only group 3
      patient (D+/R-) and all eight group 4 patients (D-/R-) were negative. CONCLUSION:
      TaqMan PCR is a reliable method for HCMV DNA quantification. In three patients
      (anti-HCMV-IgG positive) who received an anti-CMV-IgG negative transplant HCMV
      DNA was isolated. In contrast, no HCMV-DNA was evident in HCMV-negative patients
      who received an HCMV-negative transplant. Accordingly, the risk of HCMV
      reactivation is more probable than the risk of reinfection.

PMID- 14648254
TI  - [New concepts in image assisted surgery: automated patient registration based on
      the jaw and external ear].
AB  - OBJECTIVE: Automatic and marker less patient registration based on natural
      anatomical interfaces may considerably reduce the radiation load and logistical
      input prior to computer-assisted surgical interventions, as it is not necessary
      to place and measure reference markers. The present study was to find out if,
      apart from the facial skin, also auricles as well as the upper and lower jaw can
      be used as anatomical interfaces for the intraoperative registration of the
      patient's position. MATERIAL AND METHOD: Prior to surgical intervention the
      positions of 20 patients were registered by a high-resolution 3D laser scan and
      correlated with the preoperative CT data set. Tumors, skeletal malformations, and
      foreign bodies were indications for surgical intervention. Auricles as well as
      the upper and lower jaw were used to register the patient's positions. The
      accuracy of this basically marker less method was clinically evaluated through
      the additionally placed conventional registration markers. RESULTS AND
      CONCLUSION: The marker less patient registration based on natural anatomical
      interfaces was successful in the upper jaw (deviation: 0.8+/-0.3 mm). The tongue
      and mobile floor of the mouth led to geometric incongruence and inadequate laser
      registration in the lower jaw. As far as the auricles were concerned, high
      accuracy could only be achieved as long as the auricles had not been deformed
      during CT imaging (deviation: 1.9+/-0.9 mm). The usual CT acquisition with a
      conventional head support, however, led to temporary auricular deformations in
      more than half of the patients, which made an exact laser scan registration
      impossible.

PMID- 14648255
TI  - [Retrospective view of the development of malocclusion surgery and prospects].
AB  - DEVELOPMENT: The history of the correction of the jaw deformities began in the US
      more than 100 years ago with a bilateral osteotomy in a case of mandibular
      prognathism performed by Vilray Blair. This operation was the starting point for
      Blair's interest in jaw surgery. In 1907 he already described three different
      operative techniques for the correction of malpositions of the lower jaw. Between
      the First and the Second World War no major progress in corrective jaw surgery
      occurred, until in the fifties of the 20th century a rapid development started
      off. Mainly in Germany and in Austria new operative techniques not only for the
      mandible, but also for maxilla and midface were established. Finally, this
      development reached its height in the simultaneous total osteotomy of upper and
      lower jaw that was published by Obwegeser in 1970. OUTLOOK: Innovations first of
      all in regard to technical improvements especially in four fields could be
      realized within the past 20 years. For planning of a procedure mostly computer
      assisted systems combined with video- or laser technique were utilized. The
      improvement of resorbable materials such as plates and screws can be considered
      as a major progress. With regard to new operative techniques not only first
      results with navigation systems but also the introduction of endoscopic
      osteotomies were reported. Distraction osteogenesis was successfully performed on
      developmental deformities of the mandible, the maxilla, and the midface, while
      technical devices are being improved continuously. As in all fields mentioned
      above development is not yet completed further improvements can be expected.

PMID- 14648256
TI  - [Mucocele of the chin area. A rare complication after genioplasty with
      osteocartilagenous nasal bone transplant. Review of the literature and case
      report].
AB  - BACKGROUND: This paper describes an infrequent case of an intraosseous mucocele
      after chin augmentation using a nasal osseocartilaginous graft. Diagnostics,
      therapy, and clinical course of this rare complication are discussed based on our
      own experience and a review of the current scientific literature. CASE REPORT:
      Radiological examination of a 22-year-old patient revealed an oval lucent area
      approximately 3x1 cm in size with sclerotic rim. Cartilaginous material directly
      fused to the cyst wall was detected during surgery. The results of histological
      examination indicated parts of a cyst wall lined with respiratory epithelium
      located over normally maturing cartilaginous tissue. Postoperative long-term
      drainage with consecutive reduction of the cyst lumen was followed by cystectomy
      and concurrent osteoplasty and onlay graft. DISCUSSION: This case presented here
      is-as far as we know-one of three manifestations of a respiratory implantation
      cyst published. Its origin is most likely based on epithelium-like cells that
      have been incompletely removed from the resected nasal hump. Although severe
      complications of this technique have rarely been described, the surgeon must be
      aware of possible long-term side effects and should meticulously remove adherent
      nasal mucosa from the graft.

PMID- 14648257
TI  - Use of psi(alpha)-ETOs in the unified treatment of electronic attraction,
      electric field and electric field gradient multicenter integrals of screened
      Coulomb potentials over Slater orbitals.
AB  - In this study, using complete orthonormal sets of Psi(alpha)-ETOs (where alpha=1,
      0, -1, -2, ...) introduced by the author, a large number of series expansion
      formulae for the multicenter electronic attraction (EA), electric field (EF) and
      electric field gradient (EFG) integrals of the Yukawa-like screened Coulomb
      potentials (SCPs) is presented through the new central and noncentral potentials
      and the overlap integrals with the same screening constants. The final results
      obtained are valid for arbitrary locations of STOs and their parameters.

PMID- 14648258
TI  - Age and sequence of eruption of permanent teeth in Kelantan, north-eastern
      Malaysia.
AB  - The aim of this study was to determine the age and sequence of eruption of
      permanent teeth, as well as gender differences, in children and adolescents in
      Kelantan, Malaysia. Cross-sectional data on permanent teeth eruption were
      collected by examining pre-school, primary and secondary school children of 5-17
      years of age. The subjects were drawn by multistage random sampling from the
      school registers. There were 2,382 subjects in the sample, 1,062 boys and 1,320
      girls. The data were subjected to probit regression analysis. The mean age of
      eruption of lower first molar was 6.0 (95%CI: 5.8, 6.2) years. The median age of
      eruption of each tooth was earlier in girls than in boys. Although the range of
      years during which the permanent teeth erupted was similar in both sexes, i.e. 6
      12 years, the sequence of the tooth eruption differed. All mandibular teeth, with
      the exception of first and second premolars in both males and females, tended to
      erupt earlier than their maxillary counterparts. The findings seem to correspond
      to earlier studies done in the other parts of the world.

PMID- 14648259
TI  - Potentials of ultrasound in the diagnosis of midfacial fractures*.
AB  - The aim of this study was to evaluate the application and limitation of
      ultrasound in the diagnosis of midfacial fractures. Eighty-one patients with
      radiologically proved fractures of the facial skeleton were included in this
      study. Examinations were performed using a 7.5-MHz small-part applicator. Another
      ten patients without facial fractures served as controls with normal
      sonoanatomical findings. The most important deficiency of ultrasound in the
      diagnosis of midfacial fractures is the difficult detection of non-dislocated
      fractures. According to our own experiences, the application of ultrasound in
      midfacial fractures is most useful for visualization of the zygomatic arch and
      the anterior wall of the frontal sinus, with immediate imaging after closed
      reduction avoiding radiation exposure. Moreover, it is restricted to fractures of
      the orbital margin and nasal bone. If ultrasound is performed as the first
      imaging modality in cases of suspected facial fractures by an experienced
      investigator, the visualization of fracture lines can avoid conventional imaging,
      so that only an indicated CT scan can be added. In doubtful cases, an individual
      combination of conventional radiographs would be the next step. By this, an
      overall reduction of radiation exposure seems possible.

PMID- 14648260
TI  - Risk factors for nontraumatic osteonecrosis of the femoral head after renal
      transplantation.
AB  - We investigated risk factors for osteonecrosis of the femoral head (ONF) in renal
      transplant recipients, who are susceptible to the disease. Among 287 renal
      transplant recipients, 18 ONF patients with enough data were included, and 18 age
      and sex-matched recipients without ONF were nominated as reference cases. Risk
      factors were analyzed using a conditional logistic regression method. There were
      no differences between the ONF patients and the reference cases regarding the
      types of immunosuppressant or the donor (living or cadaveric, father or mother,
      matching blood type and human leukocyte antigens). The daily oral steroid dosage
      (prednisolone 25.0 mg/day or more) and blood urea nitrogen level 2 months after
      transplantation were the only factors with relevance to the occurrence of ONF. We
      propose that oral steroid dosages should be low or reduced after renal
      transplantation, and acute rejection should be controlled with pulsed therapy.

PMID- 14648261
TI  - Intentional marginal excision of osteosarcoma of the proximal fibula to preserve
      limb function.
AB  - Three cases of osteosarcoma (stage IIB) of the proximal fibula were successfully
      treated by marginal excision that preserved the common peroneal nerve and lateral
      stabilizers of the knee joint. Caffeine-assisted chemotherapy was administered to
      three boys, ages 15, 17, and 11 years, and resulted in a complete response. Two
      patients initially presented with peroneal nerve palsy that resolved completely
      with preoperative chemotherapy. The subsequent intentional marginal procedures
      resulted in preservation of the common peroneal nerves, lateral collateral
      ligaments, and biceps femoris tendons. In two cases the collateral ligament and
      biceps tendon were reattached to the tibia with a spike washer or suture anchors,
      and in the third case they were reattached by suture only to the ligamentous and
      capsular structure of the tibia. All three patients have normal ankle and knee
      joint function without evidence of recurrence 122, 120, and 61 months after
      surgery, respectively. Preservation of limb function without compromising the
      principles of tumor surgery is a desirable goal in any patient but particularly
      in young patients. For patients with osteosarcoma of the proximal fibula, this
      approach provides a better quality of life than conventional wide excision.

PMID- 14648262
TI  - Three-dimensional gait analysis of adults with hip dysplasia after rotational
      acetabular osteotomy.
AB  - Dysplasia of the hip, the most common cause of secondary coxarthrosis, has a
      relatively high prevalence in Japan. Rotational acetabular osteotomy (RAO) is an
      interventional strategy that seeks to reduce the abnormal amount of high stress
      concentration in the acetabulum and thereby to prevent the development of
      coxarthrosis. Long-term clinical results have been reported, but functional
      evaluations of the gait before and after RAO are underreported. The aim of our
      recently initiated long-term prospective study is to assess the effect of RAO on
      the gait characteristics of patients using quantitative gait analysis. Thus far
      22 patients (1 male, 21 females; mean age 30 years, range 15-43 years) have been
      enrolled, treated, and completed the preoperative and postoperative gait
      analyses. Hip pain during walking decreased in all patients after the RAO. The
      postoperative hip extension motion angle on the treated side increased
      significantly and correlated positively with the improvement in the Japanese
      Orthopaedic Association (JOA) pain score. The current study shows that coxalgia
      and gait function improved after RAO.

PMID- 14648263
TI  - Bone mineral density after removal of rigid plates from forearm fractures:
      preliminary report.
AB  - Bone mineral density (BMD) was measured on three occasions following removal of
      metal plates used to fixate diaphyseal forearm fractures in eight patients (mean
      age 38.5 years). At plate removal the mean BMD of the distal radius/ulna and the
      ulnar shaft sites were, respectively, 10.2% and 2.1% lower than on the
      nonfractured side. The apparent volumetric BMD (BMDvol) at the ulnar fracture
      site was 4.3% lower. At 6 months follow-up ( n = 5) the mean ulnar shaft BMD had
      increased by 6.4% ( P = 0.04), resulting in complete recovery of BMD, whereas the
      increase in BMDvol did not reach the BMDvol of the control side. No recovery was
      found at the distal radius/ulna site. We conclude that there is a small,
      partially reversible bone density deficit in the ulnar shaft that has been
      underneath the plate. Although the decreased bone density may in part be
      responsible for increased refracture risk at the fracture site immediately after
      plate removal, it is negligible after 6 months. The cessation of the effects of
      stress shielding is probably responsible for the increased bone density after
      plate removal.

PMID- 14648264
TI  - Efficacy of extracorporal shock-wave treatment for calcific tendinitis of the
      shoulder: experimental and clinical results.
AB  - The effects of various extracorporal shock wave energy levels and impulse rates
      were investigated using an in vitro model. In addition, we performed a
      controlled, randomized study to examine the clinical outcome after treatment for
      calcific tendinitis of the shoulder. Two groups of 40 patients each received 2000
      impulses twice with an energy flux density of 0.23 mJ/mm(2) and then 0.42
      mJ/mm(2). The results were evaluated by the Constant and Murley score.
      Disintegration of the implanted deposits requires an energy of at least 0.42
      mJ/mm(2) and 2000 impulses. The clinical trial showed resorption of calcific
      deposits in 37.5% (0.23 mJ/mm(2)) and 55.0% (0.42 mJ/mm(2)). After 1 year the
      Constant and Murley score increased from 46 to 68 at 0.23 mJ/mm(2) and from 48 to
      73 points at 0.42 mJ/mm(2). Based on our experimental and clinical results it is
      evident that disintegration of calcific deposits is dose-dependent. Because of
      the time that elapses until changes became evident on the radiographs, an instant
      and sole mechanical effect on the calcific deposits is unlikely. Therefore, a
      combined mechanical and cellular mechanism for absorption of the calcific
      deposits must be presumed.

PMID- 14648265
TI  - Rotational injuries of the distal tibial growth plate.
AB  - Nine rotational injuries of the distal tibial growth plate in combination with
      spiral fracture of the fibula were treated in our department between 1993 and
      2000. The average age of the patients was 12 years. The injury was a result of
      sudden, forceful external rotation of the ankle and foot. Pain and slight
      swelling of the ankle and external rotation of the distal tibia of 20 degrees -40
      degrees were present. Radiologically, irregularity and widening of the growth
      plate of the distal tibia were obvious. In all these cases we noted, on lateral
      views, the characteristic sign of an "open fish mouth," due to the changes in the
      shape of the physeal plate. The spiral fracture of the fibula was not obvious in
      all radiographic views. The treatment in all eight fresh cases was closed
      reduction and manipulation by reversing the mechanism of injury and long leg cast
      application in all nine cases (including the one neglected case) for 6-8 weeks.
      The final results were either excellent or very good in all nine patients after a
      mean follow-up of 6 years.

PMID- 14648266
TI  - Long-term outcome of MacIntosh reconstruction of chronic anterior cruciate
      ligament insufficiency using fascia lata.
AB  - The purpose of this study was to assess the long-term outcome of the MacIntosh
      lateral-substitution over-the-top anterior cruciate ligament (ACL) reconstruction
      in 82 patients (84 knees) at an average follow-up of 9.8 years. In this
      retrospective cohort study patients were evaluated with subjective questionnaires
      and by clinical and radiographic examination. Using the Lysholm score, 17 knees
      were rated excellent, 35 good, 19 fair, and 13 poor. The pivot shift test was
      negative in 74 patients. Altogether, 30 knee radiographs were evaluated. The mean
      Hospital for Special Surgery ACL radiographic score was 20.9. There was a non
      significant association between the radiographic score and the Lysholm score and
      between a worsening radiographic score and increasing time from injury. The
      MacIntosh lateral-substitution over-the-top ACL reconstruction shows results
      comparable to those of previously reported long-term studies. Although
      endoscopically assisted intraarticular reconstructions with faster rehabilitation
      protocols have now become popular, this procedure may be considered in patients
      needing an intra- and extraarticular reconstruction in whom cosmesis is not an
      issue.

PMID- 14648267
TI  - Intramedullary nailing of the femur with an inflatable self-locking nail:
      comparison with locked nailing.
AB  - We report a comparative study between an inflatable expandable nail and a
      traditional locked intramedullary implant in closed fractures of the femoral
      shaft. We matched each of 43 patients who had undergone intramedullary fixation
      with an inflatable expandable nail with a patient of the same sex, age (within 2
      years), and fracture who had undergone statically locked intramedullary fixation
      with traditional nails. The mean duration of surgery was significantly shorter in
      the patients who were treated with the inflatable expandable nail. There were no
      differences in average blood loss, transfusion requirements, or hospitalization.
      Five of the patients who underwent traditional nailing required dynamization to
      achieve union. The inflatable expandable nail allows effective management of
      diaphyseal fractures of the femur. Interlocking is not necessary, operative times
      are reduced, and exposure to ionizing radiation is minimized. At present,
      however, the inflatable expandable nail used in the this investigation is
      markedly more expensive than traditional devices.

PMID- 14648268
TI  - Gradual closed correction of equinus contracture using the Ilizarov apparatus.
AB  - We treated 16 patients with equinus contracture using the Ilizarov method without
      open soft tissue release. No hinge was used in seven patients; instead, their
      ankle joint was used as the hinge (natural hinge; unconstrained construct). In
      the remaining nine patients, medial and lateral hinges connecting the tibial and
      foot rings were placed at the center of the talar dome (rotating hinge;
      constrained construction). We assessed the results in terms of the extent of
      dorsiflexion, its improvement, and complications. There was little difference
      between the results in the natural hinge group and the rotating hinge group. The
      natural hinge system is therefore the method of choice for treating equinus
      contracture because it is less invasive and simpler. However, particular care is
      needed during correction to avoid complications such as anterior subluxation of
      the talus and joint space narrowing. When complications do occur, intervention
      should be immediate.

PMID- 14648269
TI  - Effect of calf-thigh intermittent pneumatic compression device after total hip
      arthroplasty: comparative analysis with plantar compression on the effectiveness
      of reducing thrombogenesis and leg swelling.
AB  - The purpose of this study was to evaluate the efficacy of two intermittent
      pneumatic compression devices as prophylaxis against intravascular coagulation
      and leg swelling following total hip arthroplasty. We studied 121 patients by
      assessing thrombogenesis using the D-dimer level before and after total hip
      arthroplasty. In addition, the patients' postoperative swelling was evaluated by
      measuring the thigh and lower leg circumference. Altogether, 58 patients were
      assigned to the calf-thigh pneumatic compression group, and the other 63 were
      assigned to the plantar compression group; the two pneumatic compression devices
      were compared to evaluate which was more effective for reducing thrombogenesis.
      At 7 days postoperatively, the mean D-dimer levels of the calf-thigh compression
      group and the plantar compression group were 8.86 and 9.26 microg/ml,
      respectively. There was no significant difference ( P = 0.697) between the two
      groups. However, the increased ratio of the circumference of the thigh, which was
      compared after arthroplasty, averaged 1.22% in the calf-thigh compression group
      and 3.19% in the plantar compression group, which was significantly different ( P
      << 0.01). Calf-thigh pneumatic compression was found to be more effective than
      plantar compression for reducing thigh swelling during the early postoperative
      stage.

PMID- 14648270
TI  - Minimally invasive uncemented total hip arthroplasty through an anterolateral
      approach with a shorter skin incision.
AB  - Total hip arthroplasty using a short skin incision has been associated with great
      controversy. It has still not yet been demonstrated that a shorter skin incision
      is efficient or safe for patients. Here, we review 212 cases of uncemented total
      hip arthroplasty performed since 1999 using the anterolateral approach and a
      shorter skin incision. Patients were divided into three groups according to the
      length of the incision at the end of surgery; incisions of 10 cm or less were
      defined as "mini" ( n = 115) and incisions of 10-15 cm as "short" ( n = 70);
      these two groups were defined as shorter skin incision groups. Incisions longer
      than 15 cm in patients undergoing the standard procedure were defined as
      "conventional" and served as the controls ( n = 27). Statistically significant
      differences were found with regard to operative duration and intraoperative blood
      loss: the shorter the length of the incision, the shorter the operative duration
      and the smaller the intraoperative blood loss. There was no significant
      difference in postoperative bleeding or in the incidence of complications among
      the three groups. Total blood losses in the shorter groups were each
      statistically significant less than that in the conventional group. Comparing the
      mini group to the short group, the length of the skin incision was influenced by
      the body mass index (BMI) and gender. For those with a high BMI and for male
      patients, a slightly longer incision was necessary. We concluded that total hip
      arthroplasty through a mini or short incision was indeed efficient for patients
      compared with total hip arthroplasty using a conventional incision.

PMID- 14648271
TI  - Bone-preserving prosthesis with a single axis for treating osteonecrosis of the
      femoral head: midterm results for the thrust plate hip prosthesis.
AB  - We studied 27 patients (31 joints) who underwent total hip arthroplasty (THA)
      using the thrust plate hip prosthesis (TPP) for osteonecrosis of the femoral
      head. The mean follow-up period was 56 months (range 38-72 months). Clinical
      evaluation by the Merle d'Aubigne and Postel system showed a significant
      improvement from a preoperative mean score of 8.1 to a final mean follow-up score
      of 16.6. Mechanical loosening developed about 1 year postoperatively in one joint
      with a bone defect. Grade 1 stress shielding was observed in four joints.
      Although indications for the TPP are restricted to certain cases, unlike the
      conventional intramedullary stem, much can be expected of TPP. It is an
      outstanding prosthesis for osteonecrosis of the femoral head of young patients in
      terms of bone preservation and physiological load transfer.

PMID- 14648272
TI  - Clinical effectiveness of antibiotic-impregnated cement spacers for the treatment
      of infected implants of the hip joint.
AB  - It is difficult to treat an infected implant of the hip joints, as it requires
      long-term treatment and eventually may lead to amputation or arthrodesis,
      involving immeasurable physical and psychological suffering for the patient. We
      utilized antibiotic-impregnated cement spacers for 17 infections after total hip
      arthroplasty and bipolar arthroplasty with good clinical results. We thoroughly
      removed any foreign material and formed an antibiotic-impregnated cement spacer
      into a shape similar to that of the implants. This enabled high-concentration
      antibiotics to act on the infected sites. It also can prevent leg-length
      discrepancy and atrophy of bones or muscles. Although cement spacers have been
      reported to have problems regarding shape and strength, we achieved good results
      with cement spacer molds in the present study. All revision surgeries were
      performed using a two-stage procedure. No infection has recurred at a mean follow
      up of 3 years 2 months.

PMID- 14648273
TI  - BMP-2 and CDMP-2: stimulation of chondrocyte production of proteoglycan.
AB  - A hallmark of intervertebral disc degeneration is loss of proteoglycans.
      Cytokines may be used to stimulate proteoglycan production in the disc to reverse
      or prevent disc degeneration. The effects of bone morphogenetic protein 2 (BMP-2)
      and cartilage-derived morphogenetic protein 2 (CDMP-2) (singly and jointly) on
      proteoglycan synthesis by a chondrocytic cell line (MC615) were studied. MC615
      cells were dosed with BMP-2, CDMP-2, or both, cultured for 6 days, and then
      assayed as follows: (1). The proteoglycan content of the medium and extracellular
      matrix were determined by dimethyl-methylene blue staining; (2). cell numbers
      were determined after 6 days of culture using the Hoechst dye DNA assay; (3).
      aggrecan mRNA was measured with the reverse transcription-polymerase chain
      reaction and Northern blotting assays. Both BMP-2 and CDMP-2 significantly
      enhanced proteoglycan production and aggrecan mRNA expression in a dose-dependent
      manner, although BMP-2 is more effective than CDMP-2 in increasing sulfated
      proteoglycan production. But BMP-2 and CDMP-2 have only a slight, nonsignificant
      effect on cell proliferation. There is no evidence of antagonism or synergy
      between the two growth factors in the aggrecan gene expression.

PMID- 14648274
TI  - Stress shielding of patellar tendon: effect on small-diameter collagen fibrils in
      a rabbit model.
AB  - The purpose of this study was to assess the effects of stress shielding on the
      microstructure and ultrastructure of the patellar tendon using 40 mature female
      Japanese white rabbits. The patellar tendon was completely released from stress
      by drawing the patella toward the tibial tubercle with a stainless steel wire
      installed between them. Microstructurally, stress shielding for 3 and 6 weeks
      increased the number of cells approximately fivefold, to that of the control
      tendon. Collagen bundles were less well oriented in the stress-shielded tendon
      than in the control. Ultrastructurally, small collagen fibrils with a diameter of
      less than 90 nm increased in the stress-shielded tendon. The median collagen
      fibril diameter in 6-week stress-shielded tendon was significantly smaller ( P <<
      0.05) than in the control tendon (58.8% of control). The ratio of the total area
      of collagen fibrils to the whole visualized area in the stress-shielded patellar
      tendon was significantly smaller at 3 and 6 weeks than that in the control. This
      study demonstrated that complete stress shielding significantly affects the
      microstructure and ultrastructure of the patellar tendon

PMID- 14648275
TI  - Statin stimulates bone morphogenetic protein-2, aggrecan, and type 2 collagen
      gene expression and proteoglycan synthesis in rat chondrocytes.
AB  - Statins increase bone morphogenetic protein-2 (BMP-2) mRNA expression and
      subsequently increase new bone formation in vitro. However, the action of statins
      on the BMP-2 mRNA regulation of cartilage matrix synthesis by chondrocytes is
      unknown. We evaluated regulation of BMP-2, aggrecan, and type II collagen (COL2)
      mRNA and (35)S-labeled proteoglycan (PG) synthesis by mevastatin using cultured
      chondrocytes obtained from articular cartilage of fetal rats. Expression of BMP
      2, aggrecan, and COL2 mRNAs were increased in the presence of 2 microM mevastatin
      on day 2. However, longer (10 day) culture in the presence of the drug decreased
      the expression of these mRNAs. PG synthesis was increased 3 days after treating
      the cells with mevastatin, which was also decreased with longer (10 day)
      mevastatin treatment. These results suggest that mevastatin increases mRNA
      expression of BMP-2, aggrecan, and COL2 as well as PG synthesis by fetal rat
      chondrocytes early in the treatment period. We suggest that statins have
      implications for fracture and cartilage repair.

PMID- 14648276
TI  - Changes in the antiangiogenic properties of articular cartilage in
      osteoarthritis.
AB  - Avascularity is important for the unique biomechanical properties of articular
      cartilage, and normal cartilage actively repels vascular invasion. This study
      investigated whether the antiangiogenic properties changed in the presence of
      osteoarthritis (OA) by culturing explants of human articular cartilage on the
      chorioallantoic membrane (CAM) of chick embryos and investigating the incidence
      of vascular invasion and the effects of exogenous vascular endothelial growth
      factor (VEGF) and matrix metalloproteinase-9 (MMP-9). The results were compared
      with those of non-OA cartilage obtained after femoral neck fractures. Altogether,
      72% of OA samples but only 5% of non-OA samples were invaded by the CAM,
      indicating that changes in the antiangiogenic properties represented a
      fundamental difference between control and OA cartilage. Exogenous VEGF or MMP-9
      increased the frequency of invasion to 70%-100%. Invasion most frequently
      occurred into cartilage matrix from which proteoglycans had been lost, the latter
      being detectable by sirius red staining of cartilage collagen. VEGF was
      synthesized by chondrocytes in proportion to the severity of degradation and
      might exacerbate the loss of resistance to invasion. These results indicate that
      loss of resistance to vascular invasion distinguishes OA cartilage from normal
      articular cartilage, which may be important in the pathogenesis of OA.

PMID- 14648277
TI  - Experimental study of osteoplastic laminectomy in the lumbar spine of rabbits.
AB  - Osteoplastic laminectomy has been used to treat lumbar canal stenosis and to
      prevent postoperative lumbar spinal instability by reconstructing the posterior
      element of the lumbar spine, which has been documented in many clinical studies.
      However, the biological sequence of repairing the posterior lumbar element, which
      is replaced at the time of surgery, has not yet been made clear. An in vivo
      rabbit study was designed to observe the biological sequence of repairing the
      replaced posterior element of the lumbar spine. Twenty-one adult rabbits
      underwent osteoplastic laminectomy at the L6. Animals were killed at 2, 4, 8, 12,
      26, and 52 weeks after surgery. The samples of the L6 vertebra, which contained
      the replaced lamina and spinous process, were analyzed by radiography, computed
      tomography (CT), and a histological method. Overall, radiograms demonstrated
      clearly the union of interarticular osteotomized sites from 4 to 8 weeks. CT
      findings revealed that the union of interarticular osteotomized sites could be
      confirmed beginning at 12 weeks, and that postoperative narrowing of the lumbar
      spinal canal had not occurred in the rabbit model. The biological sequence of
      repairing the replaced lamina and spinous process was characterized by slowly
      progressive creeping substitution, with continuous remodeling.

PMID- 14648278
TI  - Osteosarcoma arising from desmoplastic fibroma treated 16 years earlier: a case
      report.
AB  - We present a rare case of malignant transformation of desmoplastic fibroma in a
      37-year-old man. In 1984 we performed curettage and bone grafting for a bone
      tumor of the left distal femur. Histologically, we obtained a final diagnosis of
      desmoplastic fibroma. After this treatment, the patient had no particular
      symptoms but felt tension in the left knee in 2000 and consulted our department.
      We performed tumor curettage and bone grafting although malignant findings were
      recognized by imaging. The last pathology diagnosis was an osteosarcoma (in view
      of the formation of an osteoid). We performed caffeine-assisted chemotherapy and
      an additional wide excision. In the literature, two reports of a high-grade
      sarcoma developing in a desmoplastic fibroma have appeared. It is sometimes
      difficult to distinguish desmoplastic fibroma from low-grade fibrosarcoma or
      intraosseous-type osteosarcoma, although the radiographic findings and aspects of
      the resected specimen in 1984 were typical of a desmoplastic fibroma. Moreover,
      from a clinical standpoint, because the recurrence came 16 years after the
      initial operation, and lung metastasis was not seen, it is difficult to believe
      this case was malignant originally. This extremely rare lesion is believed to be
      a desmoplastic fibroma transformed to osteosarcoma.

PMID- 14648279
TI  - Abducens nerve palsy as a rare complication of spinal surgery: a case report.
AB  - We describe a case of diplopia due to abducens nerve palsy after upper cervical
      spinal surgery. A 22-year-old woman presented with a chief complaint of numbness
      and weakness in her left hand. A spinal cord tumor was detected at the C1/2
      level. These complaints disappeared after resection of the spinal cord tumor;
      however, she presented with diplopia due to abducens nerve palsy 3 days after
      surgery. Brain computed tomography and magnetic resonance imaging revealed no
      abnormalities. Within 1 month there was complete spontaneous resolution of the
      abducens nerve dysfunction. It is important for spinal surgeons to be aware of
      cranial nerve palsy as a potential complication of cervical spinal surgery.

PMID- 14648280
TI  - Irreducible palmar dislocation of the proximal interphalangeal joint caused by a
      fracture fragment: a case report.
AB  - We present a case of irreducible palmar dislocation of the proximal
      interphalangeal joint of the little finger caused by entrapment of a fracture
      fragment attached to the collateral ligament. The bony fragment was trapped
      between the radial condyle of the proximal phalanx and the volar plate. Reduction
      was easily accomplished by hooking out the fragment.

PMID- 14648281
TI  - Isolated plantar dislocation of the middle cuneiform: a case report.
AB  - Isolated plantar dislocation of the cuneiform was reported in only two cases in
      the literature. We report a 57-year-old man with plantar dislocation of the
      cuneiform when the foot was struck by a large concrete block during construction
      of a building. Tarsometatarsal injuries are frequently overlooked. Therefore,
      plain computed tomography (CT) and three-dimensional CT are useful for adequate
      evaluation.

PMID- 14648282
TI  - Amyotrophic lateral sclerosis: frequent complications by cervical spondylosis.
AB  - Cervical spondylosis is associated with myelopathy and radiculopathy, which
      sometimes mimic clinical manifestations of amyotrophic lateral sclerosis (ALS), a
      fatal neurodegenerative disorder that affects upper and lower motor neurons.
      Cervical spondylosis may coexist with ALS because both diseases preferentially
      affect individuals of middle or old age. We investigated 63 patients with ALS to
      clarify the complications of cervical spondylosis and other spinal disorders and
      to explore the history of surgical treatment for them. We found cervical
      spondylosis in 30 patients (48%), lumbar spondylosis in 7 (13%), ossification of
      the posterior longitudinal ligament (OPLL) in 4 (6.3%), and ossification of the
      yellow ligament (OYL) in 4 (6.3%). Surgery was performed early in the course of
      the disease on the cervical spine in five patients (7.9%) and on the lumbar spine
      in one (1.6%); these patients consulted our clinic because their motor symptoms
      had progressed even after the spinal surgery. Our results indicate that nearly
      half of all ALS patients have their disease complicated by cervical spondylosis,
      and that a careful differential diagnosis for ALS is necessary before making
      decisions about spinal surgery.

PMID- 14648283
TI  - Distraction osteogenesis for treatment of bone loss in the lower extremity.

PMID- 14648284
TI  - Bone tissue incorporates in vitro gallium with a local structure similar to
      gallium-doped brushite.
AB  - During mineral growth in rat bone-marrow stromal cell cultures, gallium follows
      calcium pathways. The dominant phase of the cell culture mineral constitutes the
      poorly crystalline hydroxyapatite (HAP). This model system mimics bone
      mineralization in vivo. The structural characterization of the Ga environment was
      performed by X-ray absorption spectroscopy at the Ga K-edge. These data were
      compared with Ga-doped synthetic compounds (poorly crystalline hydroxyapatite,
      amorphous calcium phosphate and brushite) and with strontium-treated bone tissue,
      obtained from the same culture model. It was found that Sr(2+) substitutes for
      Ca(2+) in the HAP crystal lattice. In contrast, the replacement by Ga(3+) yielded
      a much more disordered local environment of the probe atom in all investigated
      cell culture samples. The coordination of Ga ions in the cell culture minerals
      was similar to that of Ga(3+), substituted for Ca(2+), in the Ga-doped synthetic
      brushite (Ga-DCPD). The Ga atoms in the Ga-DCPD were coordinated by four oxygen
      atoms (1.90 A) of the four phosphate groups and two oxygen atoms at 2.02 A.
      Interestingly, the local environment of Ga in the cell culture minerals was not
      dependent on the onset of Ga treatment, the Ga concentration in the medium or the
      age of the mineral. Thus, it was concluded that Ga ions were incorporated into
      the precursor phase to the HAP mineral. Substitution for Ca(2+ )with Ga(3+)
      distorted locally this brushite-like environment, which prevented the
      transformation of the initially deposited phase into the poorly crystalline HAP.

PMID- 14648285
TI  - Sequential reconstitution of copper sites in the multicopper oxidase CueO.
AB  - CueO belongs to the family of multicopper oxidases which are characterized by the
      presence of multiple copper-binding sites with different structural and
      functional properties. These enzymes share the ability to couple the one-electron
      oxidation of substrate to reduction of oxygen to water by way of a functional
      unit composed of a mononuclear type 1 blue copper site, which is the entry site
      for electrons, and of a trinuclear copper cluster formed by type 2 and binuclear
      type 3 sites, where oxygen binding and reduction take place. The mechanism of
      copper incorporation in CueO has been investigated by optical and EPR
      spectroscopy. The results indicate unambiguously that the process is sequential,
      with type 1 copper being the first to be reconstituted, followed by type 2 and
      type 3 sites.

PMID- 14648286
TI  - Sequence heterogeneity among human picobirnaviruses detected in a gastroenteritis
      outbreak.
AB  - Human picobirnaviruses characterised in this study were serendipitously detected
      in a non-bacterial gastroenteritis outbreak when specimens were examined for the
      presence of human rotaviruses using polyacrylamide gel electrophoresis. Of ten
      stool samples sent for virological examination, two, three, and one specimens
      were positive for human caliciviruses, picobirnaviruses, and both viruses,
      respectively. Partial sequences of the RNA-dependent RNA polymerase gene were
      determined for three picobirnavirus-positive samples. The sequence identity among
      these three strains was 60% to 65% for the nucleic acid and 64% to 70% for the
      deduced amino acid sequences. Phylogenetic analysis revealed that each of the
      three strains clustered with strains identified in geographically separate areas.
      In contrast, human calicivirus strains co-incidentally identified, showed
      complete nucleotide sequence identity. These findings demonstrate a lack of
      common exposure to or point of source for picobirnavirus infection, suggesting
      that the outbreak was caused by human caliciviruses. Further studies are needed
      to determine the etiologic role and to establish the taxonomic basis of
      picobirnaviruses.

PMID- 14648287
TI  - Two unrelated double-stranded RNA molecule patterns in Gremmeniella abietina type
      A code for putative viruses of the families Totiviridae and Partitiviridae.
AB  - Two double stranded (ds) RNA molecule patterns, probably of viral origin, were
      sequenced from Gremmeniella abietina var. abietina type A. The genome of
      Gremmeniella abietina RNA virus L1 (GaRV-L1) from isolate HR2 was 5133 bp and
      contained two open reading frames (ORFs). The 5'-proximal ORF coded for a
      putative coat protein (CP) and the 3'-proximal ORF encoded putative RNA-dependent
      RNA polymerase (RdRp). GaRV-L1 had sequence similarities with a previously
      described totivirus (Helminthosporium victoriae 190S virus) and two unclassified
      members of family Totiviridae ( Sphaeropsis sapinea RNA virus 1 and Sphaeropsis
      sapinea RNA virus 2). The genome of Gremmeniella abietina RNA virus MS1 (GaRV
      MS1) from isolate C5 was composed of three dsRNA molecules coding for a putative
      RdRp (dsRNA1), a putative CP (dsRNA2) and protein of unknown function (dsRNA3).
      The lengths of these dsRNA molecules were 1782, 1586 and 1181 bp, respectively.
      Sequence comparisons indicated that the GaRV-MS1 dsRNA pattern comprises a
      putative virus that is highly similar to Discula destructiva virus 1, Discula
      destructiva virus 2 and Fusarium solani virus 1 of the family Partitiviridae.

PMID- 14648288
TI  - Expression of porcine CD163 on monocytes/macrophages correlates with
      permissiveness to African swine fever infection.
AB  - Monocytes-macrophages, the target cells of African swine fever virus (ASFV) are
      highly heterogeneous in phenotype and function. In this study, we have
      investigated the correlation between the phenotype of specific populations of
      porcine macrophages and their permissiveness to ASFV infection. Bone marrow cells
      and fresh blood monocytes were less susceptible to in vitro infection by ASFV
      than more mature cells, such as alveolar macrophages. FACS analyses of monocytes
      using a panel of mAbs specific for porcine monocyte/macrophages showed that
      infected cells had a more mature phenotype, expressing higher levels of several
      macrophage specific markers and SLA II antigens. Maturation of monocytes led to
      an increase in the percentage of infected cells, which correlated with an
      enhanced expression of CD163. Separation of CD163+ and CD163- monocytes
      demonstrated the specific sensitivity of the CD163+ subset to ASFV infection. In
      vivo experiments also showed a close correlation between CD163 expression and
      virus infection. Finally, mAb 2A10 and, in a lower extent, mAb 4E9 were able to
      inhibit, in a dose-dependent manner, both ASFV infection and viral particle
      binding to alveolar macrophages. Altogether, these results strongly suggest a
      role of CD163 in the process of infection of porcine monocytes/macrophages by
      ASFV.

PMID- 14648289
TI  - Polymorphism of a specific region in gene p23 of Citrus tristeza virus allows
      discrimination between mild and severe isolates.
AB  - The pathogenicity determinants of Citrus tristeza virus (CTV) are presently
      unknown, although transgenic Mexican limes over-expressing CTV p23, an RNA
      binding protein involved in regulating the asymmetrical accumulation of viral RNA
      strands, display typical CTV symptoms. Here we compared the predominant sequence
      variants of gene p23 from 18 CTV isolates of different geographic origin and
      pathogenicity characteristics. Phylogenetic analysis of these sequences revealed
      three groups of isolates: i) mild, inducing only symptoms in lime and/or decline
      of citrus species grafted on sour orange rootstock, ii) severe, causing
      additionally stem pitting on sweet orange and/or grapefruit, and iii) an atypical
      group of isolates inciting variable symptoms. The sequences of the isolates
      located at the periphery of each group were recombinants. Pairwise comparisons of
      the predicted amino acid sequences showed that residues at positions 78-80 were
      characteristic of each group of isolates. Group-specific primers based on these
      differences allowed RT-PCR detection of each sequence type in dsRNA-rich
      preparations from infected tissues. While mild isolates contained only the
      sequence characteristic of this group, most severe isolates contained the
      sequences characteristic of their group, and additionally, sequences
      characteristic of the mild and/or the atypical groups, suggesting that the severe
      phenotype is associated with the presence of the severe and/or the atypical
      sequence types. This association can be exploited for quick detection of
      potentially damaging sequence variants and for monitoring cross protection.

PMID- 14648290
TI  - Transgenic tobacco expressing geminiviral RNAs are resistant to the serious viral
      pathogen causing cotton leaf curl disease.
AB  - Cotton, the major cash crop in Pakistan, suffers 30% losses to cotton leaf curl
      disease, caused by the geminivirus, cotton leaf curl virus DNA A, plus a
      satellite component, DNA beta responsible for symptom development with plants
      failing to produce cotton bolls. We constructed transgenic tobacco expressing
      sense and antisense RNAs representing: [i] the 5' half of the viral DNA
      replication gene, AC1, [ii] the 3' half of AC1, [iii] two overlapping genes, AC2,
      a transcription activator, and AC3, a replication enhancer. In contrast to
      controls, 25% of 72 transgenic tobacco lines tested showed heritable resistance
      [T(1) - T(3) generations]: symptom-free and no replication of DNA A or DNA beta
      even after 120 days of continuous exposure to viruliferous whiteflies. As
      geminiviral and transgene RNAs are not detected in resistant lines following
      infection, and selected uninfected resistant tobacco sense lines reveal double
      stranded and small interfering RNAs, the most likely mechanism is via post
      transcriptional gene silencing.

PMID- 14648291
TI  - Characterization of a novel rat cytomegalovirus (RCMV) infecting placenta-uterus
      of Rattus rattus diardii.
AB  - A new rat cytomegalovirus (RCMV) isolated from the placenta/uterus of a house rat
      (Rattus rattus diardii) was found to productively infect rat embryo fibroblast
      (REF) cells. The virus produced typical herpesvirus-like cytopathic effects
      characterized by a lytic infection. The well-known herpesvirus morphology was
      confirmed by electron microscopy. Its slow growth in cell culture indicated that
      the virus is belonging to subfamily Betaherpesvirinae. Electron microscopy
      techniques and immunohistochemistry confirmed the presence of herpesviral
      inclusion bodies and virus related particles in the cytoplasm and nucleus of
      infected cells. Hyperimmune serum against the Maastricht strain of RCMV revealed
      the virus identity in neutralization test, immunoperoxidase and
      immunofluorescence techniques. Despite typical characteristics of CMV, the viral
      genome is significantly different from that of Maastricht, English, UPM/Sg and
      UPM/Kn strains. The dissimilarities, which have not been reported before, had
      been confirmed by mean of restriction endonuclease analysis. The new RCMV strain,
      a virus that infects placenta and uterus of rats, has been named as ALL-03.

PMID- 14648292
TI  - A conserved zinc finger motif in the coat protein of Tomato leaf curl Bangalore
      virus is responsible for binding to ssDNA.
AB  - Tomato leaf curl Bangalore virus (ToLCBV-[Ban5]) from south India belongs to the
      genus Begomovirus of the family Geminiviridae. So far, only the DNA A component
      has been identified in this virus. In this paper we report the overexpression of
      ToLCBV-[Ban5] coat protein (CP) in E. coli and its characterization. The purified
      recombinant CP bound preferentially to ssDNA in a sequence non-specific manner.
      Deletion of 50 amino acids from the N-terminus, including a putative N-terminal
      alpha helix, did not result in the loss of binding to DNA. A search for motifs
      responsible for DNA binding indicated a conserved putative zinc finger motif in
      the CPs (corresponding to residues 65-85 in ToLCBV-[Ban 5] CP) of begomoviruses.
      The role of this motif in DNA binding was evaluated through site-directed
      mutagenesis of the conserved cysteines (C68, C72) and histidines (H81, H85)
      present within this motif to alanine. The results indicate that the zinc finger
      motif is indeed involved in binding to zinc and DNA.

PMID- 14648293
TI  - Identification of differentially expressed genes in shrimp (Penaeus stylirostris)
      infected with White spot syndrome virus by cDNA microarrays.
AB  - White spot syndrome virus (WSSV) is currently the most important viral pathogen
      infecting penaeid shrimp worldwide. Although considerable progress has been made
      in characterizing the WSSV genome and developing detection methods, information
      pertaining to host genes involved in WSSV pathogenesis is limited. We examined
      the potential of cDNA microarray analysis to study gene expression in WSSV
      infected shrimp. Shrimp cDNAs were printed as low-density arrays on glass slides
      and were hybridized with Cy3/Cy5 labeled probes derived from RNA isolated from
      healthy and WSSV-infected shrimp. Genes that code for proteins that are relevant
      to crustacean immunity, structural proteins, as well as proteins of unknown
      function were among those whose mRNA expression was altered upon WSSV infection.
      To validate the microarray data, the temporal expression of three differentially
      expressed genes, an immune gene (C-type lectin-1), a structural gene (40S
      ribosomal protein), and a gene involved in lipid metabolism (fatty acid binding
      protein) was measured in healthy and WSSV-infected shrimp by real-time RT-PCR.
      The data suggest that WSSV infection alters the expression of a wide array of
      cellular genes, and provides a framework for further studies aimed at identifying
      genes whose function may provide insight into the mechanism of WSSV infection in
      shrimp.

PMID- 14648294
TI  - The human rhinovirus internal cis-acting replication element (cre) exhibits
      disparate properties among serotypes.
AB  - It has been reported previously that the Human rhinovirus 14 (HRV-14) RNA genome
      contains a cis-acting replication element (cre) that maps to the capsid coding
      (P1) sequence [19]. Further characterization of the HRV-14 cre in the present
      study established that by moving the cre stem-loop structure downstream, adjacent
      to the 3'NCR, that its position is not critical for function. When the P1
      sequences of two closely related serotypes of HRV-14 were analyzed for the
      presence of a cre, both HRV-3 and HRV-72 were found to contain similar sequence
      at the same positions as HRV-14. Moreover, sequence at these positions produced
      structures from MFOLD analysis that closely resembled the HRV-14 cre. It was also
      discovered that neither HRV serotypes 1a or 16 harbor replication elements that
      map to the P1 segments of their genomes. Computer and mutational analyses suggest
      that the cre in these latter HRV serotypes map instead to the 2A gene, as has
      been reported for HRV-2. The putative HRV-3 cre was determined to be unable to
      support replication when placed in an HRV-14 replicon background. Similarly, the
      previously identified HRV-2 cre was unable to support replication of the HRV-14
      genome. This finding is in contrast to the cardiovirus cre, which has been shown
      to be functionally active between two members of its family, and further suggests
      that there is a close link between the evolution of the human rhinoviruses and
      the mechanisms of RNA replication.

PMID- 14648295
TI  - Occurrence and sequences of Lily mottle virus and Lily symptomless virus in
      plants grown from imported bulbs in Zhejiang province, China.
AB  - Degenerate primers were used to amplify virus sequences from imported lilies in
      Zhejiang province, China. Two viruses, Lily mottle virus (LMoV, genus Potyvirus)
      and Lily symptomless virus (LSV, genus Carlavirus) were detected, purified and
      completely sequenced from a mixed infection in a plant raised from bulbs imported
      from the Netherlands. The sequence of LMoV was 9644 nt long and encoded a
      polyprotein of 3095 amino acids with a calculated M(r) of 351.0 kDa that had only
      45.1-54.4% identity to other completely sequenced potyviruses. Phylogenetic
      analysis of the complete polyproteins of members of the genus demonstrated that
      LMoV was distantly grouped with LYSV, BYMV and ClYVV. Two partial LMoV sequences
      from different cultivars were identical to one another and very similar (98.3%
      identical nucleotides) to the corresponding region of the complete sequence.
      Analysis of the coat protein sequences of LMoV isolates revealed two subgroups,
      corresponding to the earlier "Tulip breaking virus lily strain" and "Tulip band
      breaking virus" isolates. Our newly-determined isolates showed an extremely close
      relationship to the first of these. The LSV sequence was 8393 nucleotides long
      and had the typical carlavirus genome organization. The ORF1 protein was most
      closely related to that of Blueberry scorch virus (57.2% identical amino acids).
      Sequences of 1796 nt at the 3'-end of three additional LSV isolates from
      different cultivars were very similar (>98% identical nucleotides) to the
      corresponding region of the complete sequence. This is the first report of
      complete sequences for LMoV and LSV.

PMID- 14648296
TI  - Gremmeniella abietina mitochondrial RNA virus S1 is phylogenetically related to
      the members of the genus Mitovirus.
AB  - A double stranded (ds) RNA genome of Gremmeniella abietina mitochondrial RNA
      virus S1 (GaMRV-S1) was sequenced. The length of the genome was 2572 base pairs,
      it had a very low GC content (30.6%), and sequence and length variations occurred
      in both ends of it. The genome coded for a putative 741 amino acid long RNA
      dependent RNA polymerase (RdRp) using a mitochondrial translation code.
      Comparison of the putative amino acid sequences suggested that GaMRV-S1 is a
      putative member of the genus Mitovirus.

PMID- 14648297
TI  - Pathogenicity, sequence and phylogenetic analysis of Malaysian Chicken anaemia
      virus obtained after low and high passages in MSB-1 cells.
AB  - Specific-pathogen-free (SPF) chickens inoculated with low passage Chicken anaemia
      virus (CAV), SMSC-1 and 3-1 isolates produced lesions suggestive of CAV
      infection. Repeated passages of the isolates in cell culture until passage 60
      (P60) and passage 123 produced viruses that showed a significantly reduced level
      of pathogenicity in SPF chickens compared to the low passage isolates. Sequence
      comparison indicated that nucleotide changes in only the coding region of the P60
      passage isolates were thought to contribute to virus attenuation. Phylogenetic
      analysis indicated that SMSC-1 and 3-1 were highly divergent, but their P60
      passage derivatives shared significant homology to a Japanese isolate A2.

PMID- 14648298
TI  - Some molecular characteristics of three viruses from SPVD-affected sweet potato
      plants in Egypt.
AB  - Sweet potato feathery mottle virus (SPFMV, genus Potyvirus, family Potyviridae),
      Sweet potato chlorotic stunt virus (SPCSV, genus Crinivirus, family
      Closteroviridae) and sweet potato virus G (SPVG) were detected in naturally
      infected sweet potato plants grown in the Delta region in Egypt. Before this
      study, SPVG was reported only from China. Two isolates of SPFMV and one isolate
      of SPVG were characterized for the 3'-proximal genomic sequences. Phylogenetic
      analyses indicated that the SPFMV isolates belong to the "russet crack" strain
      group (RC). Serological tests using monoclonal antibodies, and phylogenetic
      analysis of a partial sequence of the Hsp70 gene, indicated that the Egyptian
      SPCSV belongs to the so-called non-East African strain group of SPCSV.

PMID- 14648299
TI  - The complete nucleotide sequence of isolate BYMV-GDD of Bean yellow mosaic virus,
      and comparison to other potyviruses.
AB  - The complete nucleotide sequence of Bean yellow mosaic virus (BYMV) gladiolus
      isolate GDD was determined and compared to broad bean isolates BYMV-MB4 and BYMV
      S. The BYMV-GDD genome (9528 nt) was more similar to BYMV-MB4 (9532 nt) than to
      BYMV-S (9547 nt), which has "atypical" symptom expression and host range. The
      greatest variability occurred in the 5' untranslated region, P1 protein, and NIa
      VPg protein, the N-terminal two thirds of HC-Pro, and the C-terminal one third of
      P3. Each of these regions has been correlated with symptom or host differences
      between isolates of other potyviruses, and may contribute to the "atypical"
      nature of BYMV-S.

PMID- 14648300
TI  - Cloning and sequencing of Duck circovirus (DuCV).
AB  - The genome of Duck circovirus (DuCV) is circular and 1996 nts in size. Two major
      open reading frames were identified, encoding the replicase (V1) and the capsid
      protein (C1). A stem-loop structure comprising the nonamer 5'-TATTATTAC,
      conserved in all circo-, nano- and geminiviruses, was found. Unique to DuCV, the
      region between the 3'-ends of the rep and cap gene contains four repeats of a 44
      bp sequence. Phylogenetic analysis shows close relation of DuCV with Goose
      circovirus and suggests classification of DuCV as a new member of the genus
      Circovirus of the virus family Circoviridae.

PMID- 14648301
TI  - Viruses are real, virus species are man-made, taxonomic constructions.

PMID- 14648302
TI  - In memoriam Rudolf Rott (1926-2003).

PMID- 14648303
TI  - Sacroiliac joint fusion for chronic pain: a simple technique avoiding the use of
      metalwork.
AB  - A previously undescribed method for posterior fusion of the sacroiliac joint
      (SIJ) utilizing the Cloward instrumentation is presented, suitable for cases with
      chronic pain and intact ligamental structures of the SIJ. The advantages of the
      method in comparison with other described options include minimal disturbance of
      the periarticular structures, avoidance of introduction of metalwork and
      preservation of the iliac crest contour. This technique has been used in five
      cases with follow-up longer than 2 years (mean 29 months, range 25-41 months). In
      all cases there was resolution of their painful symtomatology.

PMID- 14648304
TI  - Soccer causes degenerative changes in the cervical spine.
AB  - BACKGROUND: Radiological changes and degeneration of the cervical spine have been
      previously described in soccer players. The onset of such changes was 10-20 years
      earlier than that of the normal population. The aim of this study was to assess
      these early degenerative changes in amateur active and veteran soccer players in
      a cross-sectional descriptive study using biomechanical, radiological, and
      magnetic resonance measures. METHODS: The subjects were active (<30 years; n=15)
      and veteran (>30 years; n=15) male amateur soccer players, and their age-matched
      controls ( n=13 and n=15). Biomechanical measurements were made on a cervical
      dynamometer. Dynamic radiological and magnetic resonance findings were also
      obtained and evaluated. RESULTS: The normalized mean extension moment was higher
      in the active soccer players, but the mean range of motion was lower.
      Degenerative changes were prominent in veteran players, and the sagittal diameter
      of their spinal canal at C2 to C6 was lower when compared to active players and
      controls. Magnetic resonance findings of degeneration were more prominent in
      soccer players when compared to their age-matched controls. CONCLUSION: A
      tendency towards early degenerative changes exists in soccer players most
      probably due to high- and/or low-impact recurrent trauma to the cervical spine
      caused by heading the ball.

PMID- 14648305
TI  - Colour Doppler ultrasonography for evaluation of anterior chest blood supply: the
      possible role of arterial blood supply to the costosternal junction in the
      aetiology of idiopathic scoliosis in female adolescents.
AB  - This prospective comparative study was carried out to investigate the blood
      supply to the anterior chest wall by measurement of several anatomical and
      haemodynamic flow parameters of the internal mammary artery, with the use of
      colour Doppler ultrasonography, in female scoliotics with idiopathic right convex
      scoliosis in adolescence. Previous investigations have postulated that asymmetry
      of the breasts in female adolescents may be linked with the development of right
      convex thoracic scoliosis. This breast asymmetry is supposed to be linked with
      anatomical and functional asymmetry of the internal mammary artery that is the
      main supplier to the mammary gland. However, no measurements of anatomical and
      haemodynamic parameters of the internal mammary artery have been made to justify
      or reject the hypothesis of asymmetric blood flow volume to the breasts and
      costosternal junction in female adolescent scoliotics. Twenty female adolescents
      with right convex thoracic scoliosis and 16 comparable female individuals without
      spine deformity were examined with roentgenograms (scoliotics only) to measure
      scoliosis curve, vertebral rotation and concave and convex rib-vertebra angle at
      three vertebrae (the apical, one level above and one below the apical vertebra).
      Doppler ultrasonography was used to measure, at the origin of the internal
      mammary artery, its lumen diameter, cross-sectional area, time average mean flow
      and flow volume per minute in scoliotics and controls, which were compared with
      each other. The roentgenographic parameters were compared with the
      ultrasonographic parameters in the scoliotics to disclose any relationship. The
      reliability of colour Doppler ultrasonography was high and the intra-observer
      variability low (ANOVA, P=0.92-0.94). There was no statistically significant
      difference in the ultrasonographic parameters of the internal mammary artery
      between right and left side in each individual as well as between scoliotics and
      controls. In scoliotics the right mammary artery time average mean velocity
      increases with the convex ( P<0.05) and concave ( P<0.01) rib-vertebra angle one
      level above the apical vertebrae and with the apical convex rib-vertebra angle (
      P<0.05). The right internal mammary artery flow volume per minute increases with
      convex ( P<0.01) and concave ( P<0.01) rib-vertebra angle one level above the
      apical vertebrae and with the apical convex rib-vertebra angle ( P<0.05). Left
      internal mammary artery cross-sectional area increases with convex apical rib
      vertebra angle ( P<0.01) and concave rib-vertebra angle one level above the
      apical vertebra ( P<0.01). Conclusively, this investigation showed that
      haemodynamic flow parameters of the right internal mammary artery and anatomical
      parameters of the left internal mammary artery are significantly correlated with
      the magnitude of rib-vertebra angles close to the apex of right thoracic
      scoliosis in female adolescents. This study did not find any evidence for side
      difference in vascularity of the anterior thorax wall and, thus, it could not
      clearly justify previous theories for development of right thoracic scoliosis in
      female adolescents.

PMID- 14648307
TI  - Frozen cancellous bone allografts: positive cultures of implanted grafts in
      posterior fusions of the spine.
AB  - We have carried out a study on the behaviour pattern of implanted allografts
      initially stored in perfect conditions (aseptically processed, culture-negative
      and stored at -80 degrees C) but which presented positive cultures at the
      implantation stage. There is no information available on how to deal with this
      type of situation, so our aim was to set guidelines on the course of action which
      would be required in such a case. This was a retrospective study of 112 patients
      who underwent a spinal arthrodesis and in whom a total of 189 allograft pieces
      were used. All previous bone and blood cultures and tests for hepatitis B and C,
      syphilis and HIV (via PCR techniques) were negative. The allografts were stored
      by freezing them at -80 degrees C. A sample of the allograft was taken for
      culture in the operating theatre just before its implantation in all cases. The
      results of the cultures were obtained 3-5 days after the operation. There were 22
      allografts with positive culture results (12%) after implantation. These
      allografts were implanted in 16 patients (14%). Cultures were positive for
      staphylococci coagulase negative (ECN) in 10 grafts (46%), Pseudomonas stutzeri
      in two grafts (9%), Corynebacterium jeikeium in two grafts (9%), staphylococci
      coagulase positive in two grafts (9%) and for each of the following organisms in
      one case each (4%): Corynebacterium spp., Actinomyces odontolyticus,
      Streptococcus mitis, Peptostreptococcus spp., Rhodococcus equi and Bacillus spp.
      No clinical infection was seen in any of these patients. Positive cultures could
      be caused by non-detected contamination at harvesting, storing or during
      manipulation before implantation. The lack of clinical signs of infection during
      the follow-up of our patients may indicate that no specific treatment different
      from our antibiotic protocol is required in the case of positive culture results
      of a graft piece after implantation.

PMID- 14648309
TI  - Ectomycorrhizas of Cortinarius helodes and Gyrodon monticola with Alnus acuminata
      from Argentina.
AB  - Field ectomycorrhizas of Cortinarius helodes Moser, Matheny & Daniele (sp. nov)
      and Gyrodon monticola Sing. on Alnus acuminata Kunth (Andean alder, aliso del
      cerro) are described based on morphological and anatomical features.
      Ectomycorrhizal roots were sampled beneath fruitbodies of C. helodes and G.
      monticola from two homogeneous A. acuminata forest sites located in Tucuman and
      Catamarca Provinces in Argentina. C. helodes ectomycorrhizas showed a thick white
      to beige mantle exuding a milky juice when injured, were bluish toward the apex,
      and had hyphal strands in the mantle. G. monticola ectomycorrhizas showed some
      conspicuous features like highly differentiated rhizomorphs, inflated brown cells
      on the mantle surface, and hyaline and brown emanating hyphae with dolipores.
      Restriction fragment length polymorphism analysis of the nuclear rDNA internal
      transcribed spacer provided a distinctive profile for each of the collections of
      fruitbodies and the mycorrhizal morphotypes.

PMID- 14648310
TI  - Totally implantable subcutaneous port system versus central venous catheter
      placed before induction chemotherapy in patients with acute leukaemia-a
      randomized study.
AB  - A group of 43 adult patients with acute leukaemia (AL) were randomized to receive
      a double-lumen totally implantable subcutaneous port system (PORT, n=19) or a
      double-lumen central venous catheter (CVC, n=24) before induction chemotherapy.
      Six patients were excluded due to protocol violation ( n=4, CVC) and technical
      difficulties ( n=2, PORT). A standardized catheter record form was used for
      recording of catheter function, local infection and bleeding. The study was
      prematurely closed due to extensive subcutaneous bleeding after placement in five
      patients with a PORT. Intention to treat ( n=43) or per protocol (PP) analysis (
      n=37) did not reveal a significant difference between the two groups with regard
      to catheter survival time (PP PORT, median 113 days, range 2-634 days; CVC, 55
      days, 11-223 days). The number of positive blood cultures per 100 central venous
      access device days was significantly higher in the CVC group (median 3.6 per 100
      days) than in the PORT group (0.9 per 100 days; P=0.02). In addition, the time to
      the first blood culture positive for coagulase-negative staphylococcus was
      shorter in the CVC group (median 14 days) than in the PORT group (52 days;
      P=0.02). Despite fewer infectious complications in the PORT group the use of a
      double-lumen CVC is advocated in patients with AL undergoing induction treatment
      due to the risk of extensive local bleeding after placement of the PORT.

PMID- 14648311
TI  - [Psychosomatic aspects in the diagnosis and treatment of fibromyalgia].
AB  - The fibromyalgia syndrome (FMS) is a chronic pain condition of the
      musculoskeletal system defined by criteria of the American College of
      Rheumatology in 1990. Despite this definition, etiology and pathogenesis of FMS
      are still unknown, and consequently the therapy aims mainly at relieving
      symptoms. The favourite hypothesis is a multietiological concept including
      genetic, central nervous, muscular, and psychological issues. This article
      focuses on current psychological aspects as to etiology, process of
      chronification, and therapy of FMS. Regarding etiology there are diverging
      hypotheses rather than a general agreement, e.g. specific personality traits,
      traumatic events, psychodynamic explanations on the basis of a depressive
      conflict, or the subsumption under somatoform disorders. However, psychological
      aspects are evident to influence the course and treatment of FMS. In the
      chronification process behavioural aspects like avoidance behaviour with
      subsequent physical impairment, attitudes towards subjective theories of illness
      and therapeutic options, social factors like effects on work, interpersonal
      conditioning, and coping strategies play an important role. Therapeutic options
      of FMS comprise exercise, drugs, and psychotherapy. An integrated approach
      combining these options, a sustainable doctor-patient relationship, and a
      continuous support of the patient seem to be beneficial.

PMID- 14648312
TI  - [Musculoskeletal pain in the population].
AB  - This review of studies on the prevalence of musculoskeletal pain demonstrates the
      epidemiologic relevance of this health problem. Based on the results of the
      German National Health Survey, about 16% of the adult population is affected by
      severe musculoskeletal pain. Prevalence in women is higher than in men (women:
      18%, men: 14%) and dependent on age, with a maximum prevalence occurring around
      the age of 50 to 60. In a comparison with results on the prevalence of chronic
      widespread pain, a realistic estimate of the prevalence of clinically relevant
      musculoskeletal pain can be derived. Findings from longitudinal studies show
      considerable agreement with respect to the natural course of musculoskeletal
      pain. Known risk factors-apart from a history of pain experience-are only
      moderately associated with the occurrence and course of musculoskeletal pain.

PMID- 14648313
TI  - [Musculature as a source of back pain].
AB  - Lumbar muscle function is considered to be an important component of chronic low
      back pain (CLBP). Many studies have documented compromised muscle function in
      patients with CLBP. Although the mechanism associating muscle insufficiency to
      CLBP is not clearly understood, it is commonly held that the passive tissues of
      the spine are increasingly stressed with increasing functional muscle
      insuffiency. Functional instability of the spine plays a major role in the
      development of back pain. During the last few years, objective evaluation of the
      fatigue of back muscles by surface electromyography (EMG) with quantitative
      spectral techniques, evaluation of fibre type and size of the back muscles and
      quantifying of postural control of the lumbar spine during different tasks
      documented the failure of the spine in CLBP patients by a deficit of motor
      control more objectively. Besides this deficit, many patients show severe
      psychosocial problems and fear-avoidance beliefs. On this basis, treatment of
      CLBP with active rehabilitation, which includes educational, psychological, and
      social components along with the therapeutic exercises, has been increasingly
      advocated during recent years.

PMID- 14648314
TI  - [Diagnosis and therapy of myofascial trigger points].
AB  - AIM: Myofascial trigger points (MTrPs) are hyperirritable tender spots in
      palpable tense bands of skeletal muscle. Muscle is an orphan organ, no medical
      specialty claims muscle as its organ. The article aims at filling some of the
      gaps in the current knowledge of MTrPs. METHODS: The presented findings were
      partly obtained in experiments on anesthetised rabbits, partly they are the
      result of ample experience with patients suffering from MTrPs. DIAGNOSIS: Each
      muscle has a characteristic elicited referred pain pattern that, for active
      MTrPs, is familiar to the patient. Without a laboratory test or imaging method,
      diagnosis of MTrPs depends entirely on history and physical examination. MTrP
      symptoms follow muscle overload, are activated acutely by sudden overload, or
      develop gradually with prolonged contractions or repetitive activity. The
      diagnostic skill required depends on considerable innate palpation ability,
      authoritative training, and extensive clinical experience. THERAPY: Effective
      treatment methods include manual stretching by trigger-point pressure release,
      contract-relax, vapo coolant spray-and-stretch, and dry needling or injection of
      MTrPs. CONCLUSIONS: The integrated hypothesis presents an explanation for the
      pathophysiology of MTrPs and begins with excessive release of acetylcholine from
      involved motor endplates. It depends on a new understanding of the abnormality of
      endplate noise. Biopsies demonstrate segmental shortening of groups of sarcomeres
      in individual muscle fibres and possibly waves of contracted sarcomeres to
      account for palpable taut bands.

PMID- 14648315
TI  - [Muscular-arthroscopic pain: often unappreciated].
AB  - Myoarthropathic pain, most often due to masticatory myalgia, is the major source
      of orofacial pain. Its diagnosis is not always easy because the diagnostic signs
      are not pathognomonic and they may occur also with other pain disorders. The pain
      intensity fluctuates, and mild to medium intensity pain has the tendency to
      subside spontaneously or can be alleviated with simple, non-invasive therapies
      such as counseling, self-control, analgesics, physiotherapy, and occlusal
      appliances. For most patients a combination of counseling, self-control and
      physiotherapy (home program) is sufficient to relieve the pain. Occlusal
      appliances should, therefore, be used only if these modalities fail or if pain is
      present on awakening. Only in a small percentage of patients the myoarthropathic
      pain persists and becomes chronic. The factors that determine pain chronicity are
      complex and most likely due to the interaction of biomedical factors - such as
      the persistence of peripheral nociceptive input, neuroplastic changes at spinal
      and supraspinal levels (cortical reorganisation)- with psychosocial factors, in
      addition, possibly, to a polymorphism of the catechol-o-methyltransferase gene.
      Patients with chronic myogenic pain need a multimodal therapy, according to the
      biopsychosocial pain model. In addition to the modalities just described, the
      treatment must address also the affective, emotional, cognitive and behavioural
      pain component and be tailored to the single patient based on his/her
      psychosocial and constitutional characteristics. The goal is not pain relief but
      improvement of the quality of life by teaching the patient more efficient pain
      coping strategies by means of behavioural and relaxation techniques. In addition,
      tricyclic antidepressants may be used in order to treat the somatic pain
      component caused by the neuroplastic changes that take place in the central
      nervous system in chronic pain conditions.

PMID- 14648316
TI  - [Importance of inflammatory myopathies in practice].
AB  - Inflammatory myopathies can be subdivided into two main groups: infectious
      (bacterial, viral or other) myositis and immunogenic myositis. According to their
      frequency there are four main groups of diseases: dermatomyositis (DM), overlap
      syndromes, inclusion body myositis (IBM), idiopathic polymyositis (PM). Muscle
      weakness and atrophy are the prominent clinical symptoms of all immunogenic
      inflammatory myopathies. Muscle pain is not so common and occurs more frequently
      in acute forms than in chronic cases. Primary chronic forms of polymyositis and
      inclusion body myositis are mostly painless. Diagnosis starts with
      electromyography and laboratory investigations (especially CK). Myositis
      associated antibodies are mostly associated with acute forms. Radiological
      methods, especially MRI, are important in chronic cases. Definite diagnosis has
      to be done by muscle biopsy. Immunohistological (especially in DM and PM) and
      ultrastructural (especially in IBM) techniques are necessary in some cases.
      Concerning therapy of DM and PM, corticosteroids in combination with
      immunosuppressive drugs are effective in most cases. Intravenous immunoglobulins
      are needed only in selected cases (severe forms), side effects of therapy or
      resistance to conventional therapy. In IBM, it is the only therapeutic
      possibility, especially in young patients with rapid progression of the disease.

PMID- 14648317
TI  - [What's new in the therapy of fibromyalgia?].
AB  - Modern management of fibromyalgia (FM) requires a holistic approach, which
      includes nonpharmacologic strategies (both exercise and behavioral strategies)
      and pharmacologic treatment. Despite only partial effects in some patients,
      tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal
      antiinflammatory drugs, analgesics and opioids are in use. The use of
      antiepileptic drugs and antispasticity agents is mainly supported by anecdotal
      data. Three other classes of agents are currently thought to have useful
      potentials. N-methyl-D-aspartate-(NMDA-)mediated neurotransmission may play an
      important role in mediating wind-up and related phenomena in pain pathways.
      Recent studies have demonstrated that NMDA receptor antagonists improve pain
      symptoms in FM. But a poor side effect profile represents a significant problem.
      Cerebrospinal fluid substance P concentrations are significantly elevated in FM
      patients, but the analgesic potential of neurokinin-1 (NK1) receptor antagonists
      did not meet early expectations. Tropisetron, a 5-HT3 receptor antagonist, was
      tested in a multicenter, double-blind, randomized, placebo-controlled trial
      including 403 patients. In those receiving 5 mg tropisetron, 39.2% fulfilled the
      response criterion (pain reduction 35%) as compared to 26.2% in the placebo group
      (p=0.033). On 10 and 15 mg, the responder rates were smaller and statistically
      not significant. A total of 78 responders to therapy were followed up for 12
      months. After the end of treatment, pain intensity rose within one month in all 4
      groups. Patients having received 5 or 10 mg showed a less pronounced increase in
      pain. In addition, even 12 months after stopping treatment, pain was still
      markedly below baseline levels in the 5 and 10 mg groups.

PMID- 14648318
TI  - [What do we know about the state of chronic pain?].
AB  - Chronic pain syndromes are characterized by altered neuronal excitability in the
      pain matrix. The ability to rapidly acquire and store memory of aversive events
      is one of the basic principles of nervous systems throughout the animal kingdom.
      These neuroplastic changes take place e. g. in the spinal cord, in thalamic
      nuclei and cortical and subcortical (limbic) areas integrating pain threshold,
      intensity and affective components. Chronic inflammation or injury of peripheral
      nerves evokes the reorganisation of cortical sensory maps. Neurons conveying
      nociceptive information are controlled by various sets of inhibitory
      interneurons. The discharge activity of these interneurons counteracts long-term
      changes in the pain matrix following nociceptor activation, i. e. it prevents the
      transition of acute pain signaling to chronic pain states. Our most recent
      research suggests that pain states may be sensitive to novel families of agents
      and therapeutic measures not predicted by traditional preclinical pain models as
      well as human pain states. The endogenous cannabinoid system plays a central role
      in the extinction of aversive memories. We propose that endocannabinoids
      facilitate extinction of aversive memories via their selective inhibitory effects
      on GABAergic networks in the amygdala.

PMID- 14648319
TI  - [Assessment of muscle pain and hyperalgesia. Experimental and clinical findings].
AB  - AIM: It is evident that muscle hyperalgesia and referred pain have an important
      role in chronic musculoskeletal pain. More knowledge of the basic mechanisms
      involved and better methods of assessing muscle pain in clinical practice are
      needed so that treatment regimens can be revised and improved. METHODS: Methods
      of quantitative sensory testing of muscle pain and associated phenomena are
      described. These methods make it possible to evaluate manifestations of muscle
      pain in a standardised way both in patients suffering from musculoskeletal pain
      and in healthy volunteers. RESULTS: Elevated muscle sensitivity becomes manifest
      as (1) pain evoked by a normally non-noxious stimulus (allodynia), (2) abnormally
      intense pain evoked by noxious stimuli (hyperalgesia), or (3) unusually large
      areas of referred pain with associated somatosensory changes. These changes can
      occur as increased somatosensory sensitivity of deep somatic tissues or of the
      skin in areas of pain referral. Some manifestations of sensitisation in chronic
      musculoskeletal pain patients, such as expansion of the areas of referred muscle
      pain, can be explained by the extra segmental spread of central sensitisation
      seen in animal experiments. CONCLUSIONS: An important part of the manifestations
      of pain in chronic musculoskeletal disorders may be due to peripheral and central
      sensitisation processes, which are also involved in the transition from acute to
      chronic pain. Knowledge of these processes has expanded enormously in recent
      years; it should be utilised when new intervention strategies are designed.

PMID- 14648320
TI  - [Use of botulinum toxin the the treatment of muscle pain].
AB  - The analgesic effects of botulinum toxin (BTX) have been discussed
      controversially due to substantial placebo effects and flaws in the study designs
      used. Additionally, pathophysiological concepts of pain and the specific
      analgesic mechanisms of BTX remain largely unclear. Apart from pain reduction
      through the well-documented effects of BTX at the neuromuscular endplate,
      additional analgesic mechanisms, including other synaptic and local effects, have
      been suggested. Currently, BTX can be recommended for pain treatment in dystonia
      and spasticity. In myofascial pain syndromes, pain relief by BTX injections has
      been reported, but definite proof according to evidence-based medicinal criteria
      is still lacking. In fibromyalgia, there seems to be no analgesic effect. The
      role of BTX in pain therapy is likely to increase in the future.

PMID- 14648321
TI  - [What is different about muscle pain?].
AB  - BACKGROUND: The bulk of available knowledge about pain mechanisms is derived from
      studies on cutaneous pain. However, deep somatic pain (from muscle, fascia,
      tendon, joint) is clinically of much greater importance. The existing subjective
      differences between muscle and skin pain (e.g. muscle pain is poorly localized
      and shows referral) suggest that muscle and skin pain do not share the same
      mechanisms. AIMS OF THE STUDY: To answer the question if the nociceptive
      information from muscle has neuroanatomical connections and mechanisms that are
      distinct from those of cutaneous nociception. MATERIALS AND METHODS: The results
      were obtained partly in animal experiments on anaesthetised rats, partly in
      studies with healthy subjects or fibromyalgia patients. RESULTS: 1. At the spinal
      level, the excitatory effects of unmyelinated afferent fibres from muscle are
      subject to a strong segmental inhibition by myelinated afferent fibres, which is
      largely absent in the effects of cutaneous C fibres. 2. At the cortical level,
      experimental muscle pain excites other regions than does cutaneous pain. 3. At
      the level of descending pain-modulating pathways, interruption of the activity in
      these pathways leads to higher activity of nociceptive neurones caudal to the
      site of interruption. The activity was higher in neurones with input from deep
      nociceptors than in cells mediating cutaneous nociception. CONCLUSIONS: The data
      demonstrate that at all central nervous levels the connections and processing of
      nociceptive information from muscle and skin are different. The findings
      regarding descending pain-modulating pathways suggest that a dysfunction of this
      system could lead to chronic deep pain as in fibromyalgia.

PMID- 14648322
TI  - [Diagnosis and clinical signs of fibromyalgia].
AB  - According to the criteria of the American College of Rheumatology (ACR 1990)
      fibromyalgia can be classified as a complex of clinical symptoms. It is
      characterised by widespread muscle pain, and pain in at least 11 out of 18
      defined so-called tender points. The widespread muscle pain must be present for
      at least 3 months. For the diagnosis of fibromyalgia many other rheumatological,
      neurological and psychiatric diseases have to be excluded; additional autonomic
      or functional symptoms are usual. Routine laboratory or radiological examinations
      yield normal results. From a pathogenetic point of view endocrine disturbances
      and psychosocial stress factors are found. In most cases the clinical course
      shows a slow development of generalised pain.

PMID- 14648323
TI  - [Non-medical therapy of myofascial pain].
AB  - METHODS: In a prospective study, the efficacy of manual therapy and dry needling
      was examined in 84 patients with chronic low back pain (mean duration of pain 4.4
      years). RESULTS: The initial value of pain on the visual analogue scale was about
      6.6, the follow up value was reduced to 3.67 (p=0.0033). CONCLUSIONS: Manual
      trigger point therapy of myofascial trigger points in the low back is effective.

PMID- 14648324
TI  - [Facial pain].

PMID- 14648325
TI  - A-20C angiotensinogen gene polymorphism and proteinuria in childhood IgA
      nephropathy.
AB  - We have previously reported that the TT genotype of the angiotensinogen gene and
      the ID/DD genotype of the angiotensin-converting enzyme gene are associated with
      increased severity of proteinuria in IgA nephropathy in Japanese children.
      Recently it was reported that polymorphism at -20 from adenine to cytosine in the
      angiotensinogen gene, increasing the level of this transcript, was associated
      with the progression of renal dysfunction in adult IgA nephropathy. We therefore
      investigated whether this polymorphism is involved in IgA nephropathy in Japanese
      children. We identified this polymorphism in 105 children with IgA nephropathy
      and 119 healthy adults using polymerase chain reaction/restriction fragment
      length polymorphism analysis. At the time of biopsy, all patients had normal
      blood pressure and renal function. There were no differences in the genotypes and
      allele frequencies of this polymorphism between patients with IgA nephropathy and
      controls. The number of patients with the AC/CC genotype showing heavy
      proteinuria (>or=1.0 g/day per m(2) body surface area) at biopsy was
      significantly higher than that with the AA genotype ( P=0.039, chi-squared test).
      The AC/CC genotype of this polymorphism may be associated with an increased
      severity of proteinuria, suggesting that this polymorphism may play a significant
      role in the progression of IgA nephropathy in Japanese children.

PMID- 14648326
TI  - Recovery of renal function after long-term dialysis in hemolytic uremic syndrome.
AB  - Long-lasting recovery of renal function of the native kidneys after prolonged
      renal replacement therapy is rare. An 8-year-old girl and a 3-year-old boy had
      suffered from acute atypical and diarrhea-associated hemolytic uremic syndrome
      (HUS), respectively, with subsequent apparent end-stage renal failure. Both
      recovered renal function after long-lasting anuria and dialysis of 8 and 16
      months, respectively. After prolonged follow-up, i.e., 7 and 5 years after
      cessation of dialysis, they attained normal or slightly reduced renal function
      (plasma creatinine 84 and 90 micro mol/l, respectively). In addition, growth and
      cognitive development were normal. We conclude that caution is appropriate before
      offering early renal transplantation to pediatric patients with presumed end
      stage kidney disease secondary to HUS.

PMID- 14648327
TI  - Angiotensin II reduces calcium uptake into bone.
AB  - Children with neonatal Bartter syndrome (NBS) have hypercalciuria,
      nephrocalcinosis, and osteopenia. A complex of basic-fibroblast growth factor (b
      FGF) and a naturally occurring glycosaminoglycan has been identified in the serum
      and urine of NBS patients. This complex increases bone resorption in a bone disc
      bioassay system. Angiotensin II (AT II), which is increased in Bartter syndrome,
      increases the synthesis of b-FGF by cultured endothelial cells. Addition of 10(
      8) M AT II to the bioassay, a concentration reported in Bartter syndrome
      patients, significantly decreased calcium uptake into bone discs [E/C 0.60
      (0.04), P < 0.001 compared with buffer, normal E/C >0.90]. Adding b-FGF
      monoclonal antibody at 10 microg/ml [E/C 0.90 (0.06), P=NS] or indomethacin [E/C
      1.00 (0.03), P=NS] to 10(-8 )M AT II neutralized this effect. In separate
      experiments, newborn rats were given intraperitoneal injections of AT II. Bone
      discs from these animals were used in the bioassay system and calcium uptake was
      markedly reduced compared with discs from rats injected with phosphate-buffered
      saline [AT II 6.6 x 10(-9), E/C 0.10 (0.04), P<0.001, AT II 3.3 x 10(-8), E/C
      0.10 (0.05), P<0.001]. AT II decreases calcium uptake in the bone disc bioassay
      system. This effect can be abrogated by antibody to b-FGF or prostaglandin
      synthetase inhibition. These results support the hypothesis that in children with
      NBS, elevated levels of AT II stimulate local skeletal b-FGF synthesis, with a
      resultant increase in bone resorption via a prostaglandin-dependent pathway.

PMID- 14648329
TI  - Dent disease with compound heterozygous mutations leading to severe chronic renal
      failure in a female patient.

PMID- 14648330
TI  - Minimal change nephrotic syndrome with Guillain-Barre syndrome.
AB  - A 17-year-old white male with a diagnosis of Guillain-Barre syndrome (GBS)
      developed severe proteinuria and edema 5 days later. Renal biopsy confirmed
      minimal change nephrotic syndrome (MCNS). To our knowledge this is the first
      report of such an association between ex novo MCNS and GBS in a pediatric
      patient. The NS responded to steroid therapy. The pertinent literature is
      reviewed.

PMID- 14648331
TI  - Mycobacterial peritonitis in pediatric peritoneal dialysis patients.
AB  - Peritonitis is the most common complication and the leading cause of death in
      pediatric peritoneal dialysis (PD) patients. According to the most recent data
      available from the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS), approximately 25% of pediatric PD patients who die succumb to
      infection. There are no reported cases of Mycobacterium tuberculosis (MTB) or
      Mycobacterium avium-intracellulare peritonitis in the NAPRTCS registry. With an
      increasing incidence of MTB worldwide and the impairment of cellular immunity in
      chronic renal failure patients, it is not surprising that mycobacterium
      peritonitis can occur in PD patients. We report two pediatric PD patients with
      mycobacterial peritoneal infection diagnosed over an 11-year period at our
      institution. One patient presented with a malfunctioning Tenckhoff catheter and
      again 3 years later with hyponatremia and ascites. The other presented with
      recurrent culture-negative peritonitis. These cases illustrate the importance of
      more extensive evaluation of PD complications, to include evaluation for
      mycobacterium with special media or peritoneal biopsy, in the above clinical
      settings if the routine work-up is unrevealing.

PMID- 14648332
TI  - Fulminant meningococcemia and acute renal failure in a 3-year-old boy.
AB  - Acute renal failure is a common occurrence in sepsis, but is rarely reported in
      meningococcemia. We present a young child diagnosed with fulminant
      meningococcemia who had several poor prognostic factors, including hypotension,
      thrombocytopenia, purpura fulminans, seizures, the absence of meningitis with
      meningococcemia, and acute renal failure, which was successfully treated with
      peritoneal dialysis. Peritoneal dialysis was started on the 5th day because the
      patient had been anuric for 48 h. At that time, analysis showed that the child
      was both hypokalemic and hypophosphatemic. His serum blood urea nitrogen was 61
      mg/dl, creatinine 2.75 mg/dl, potassium 2.8 mEq/l, and phosphorus 0.7 mg/dl.
      Urine output began on the 12th day post admission and normalization of serum
      creatinine was achieved on the 26th day. In conclusion, renal failure is an
      important complication of meningococcemia and, to be effective, sometimes long
      term peritoneal dialysis is required. Profound metabolic abnormalities, such as
      hypokalemia and hypophosphatemia, may occur paradoxically in the presence of
      oliguria.

PMID- 14648333
TI  - Non-glucocorticoid-remediable aldosteronism in an infant with low-renin
      hypertension.
AB  - A 6-week-old male with severe hypertension is presented. He was found to have
      hyperaldosteronism and a negative long polymerase chain reaction (PCR) test for
      glucocorticoid-remediable aldosteronism. His mother and maternal grandfather also
      had severe hypertension. A case is made for the possible diagnosis of familial
      hyperaldosteronism type II at a very early age.

PMID- 14648334
TI  - In utero exposure to nonsteroidal anti-inflammatory drugs: neonatal renal
      failure.
AB  - We report a case of neonatal transient renal failure after maternal ingestion of
      diclofenac, paracetamol, and nimesulide during pregnancy. The baby girl was
      delivered at the 33 weeks gestation for complete absence of amniotic fluid. Acute
      renal failure was present. Urine output started 12 h after birth, increasing to
      polyuria on day 6, and then decreasing gradually to normal values. Serum
      creatinine normalized on day 6. Several cases of severe and sometimes
      irreversible renal problems have been described in neonates exposed to
      indomethacin, a non-selective cyclooxgenase (COX) inhibitor, during their fetal
      life. More recently, the use of nimesulide, a selective COX-2 inhibitor, as a
      tocolytic agent has been advocated. Although it is difficult to ascribe the
      observed side effects to one specific drug in our patient, using the Naranjo ADR
      probability scale, renal failure was probably related to nimesulide exposure.
      Paracetamol is considered safe at therapeutic doses, and there are no reports of
      prenatal diclofenac toxicity. However, recently there have been some reports of
      neonatal renal failure associated with maternal nimesulide consumption and
      probably modulated by genetic factors. Hence, cautious use of nimesulide during
      pregnancy must be advocated.

PMID- 14648335
TI  - Rapid decline of anti-pneumococcal antibody levels in nephrotic children.
AB  - Nephrotic children are at increased risk for pneumococcal infections. Antibody
      responses to the currently recommended pneumococcal polysaccharide vaccine have
      been variable and maintenance of adequate antibody levels over time has not been
      well documented. In this study, we determined total IgG antibody levels against
      pneumococcal polysaccharides before and 1, 6, 12 and 36 months after 23-valent
      pneumococcal polysaccharide vaccine (PPV) administration in nine children with
      steroid-responsive nephrotic syndrome during remission while off corticosteroids.
      The baseline antibody levels were between 4 and 86 mg/l. Four weeks after
      vaccination, the titer increased at least twofold in all patients with a mean
      arithmetic value of 165.4 mg/l. At the 6th month, the levels decreased in six out
      of nine subjects to a mean of 94.6 mg/l. At the 36th month, the control antibody
      levels were below the baseline or below the early postvaccination values in four
      out of nine subjects. Only two patients had stable high concentrations through
      the study period. Our data show that nephrotic patients may not retain their
      antibody levels despite reasonably good initial responses to the pneumococcal
      vaccine and that susceptibility to infections may continue in vaccinated
      children.

PMID- 14648336
TI  - Really sterile pyuria with Kawasaki disease?

PMID- 14648337
TI  - A boy with mitochondrial disease: asymptomatic proteinuria without neuromyopathy.
AB  - Mitochondrial disorder is a relatively rare disease during childhood. Previous
      studies concluded that renal complications in this disease most often occur in
      patients with mitochondrial encephalomyopathies. We describe a boy with
      mitochondrial disease who presented with proteinuria while lacking neuromyopathy.
      Proteinuria was detected at the age of 6 years, including large amounts of low
      molecular-weight proteins such as beta(2)- and alpha1-microglobulin. Renal
      functions were normal. Proximal tubular dysfunction and other renal
      manifestations were absent. Episodic neurologic problems such as migraine and
      nervous system diseases including epilepsy, depression, schizophrenia and
      amytrophic lateral sclerosis (ALS) were found in the boy's family members. Renal
      tubular basement membrane atrophy and interstitial fibrosis with mononuclear cell
      infiltration were observed. Ultrastructural examination showed mitochondria,
      mainly in the proximal tubules, which varied in size and had disoriented cristae.
      Mutation analysis using mitochondrial DNA (mtDNA) extracted from renal tissues
      demonstrated a A-->G point mutation at nucleotide position 3243 in the
      tRNA(Leu(UUR)) gene, while there was no mutation found in mtDNA extracted from
      peripheral leukocytes. Awareness among pediatricians of mitochondrial disorders,
      detection of low-molecular-weight proteinuria, renal ultrastructural examination
      and mutation analysis of mtDNA obtained from renal tissues could be important for
      early diagnosis of this disease.

PMID- 14648338
TI  - Outcome of pediatric renal transplants in a developing country.
AB  - This study was conducted to evaluate the outcome of pediatric renal transplants
      at our center. A retrospective analysis was done on 39 pediatric transplants (age
      at transplant <18 years) done at our center over the last 10 years. The mean age
      at transplant was 15.6+/-1 years (10-17 years). They comprised 4.2% of all renal
      transplants done at our center (39/921) over the period. Girls comprised 17.5% of
      total recipients ( n=7). Two patients had a preemptive transplant. The underlying
      causes of end stage renal disease were chronic glomerulonephritis ( n=21),
      chronic interstitial nephritis ( n=17) and Alport syndrome [1]. All the 39
      children were initiated on triple drug immunosuppression (cyclosporin A (CsA)
      azathioprine, prednisolone). All patients received grafts from living related
      donors. In the first month, three patients had graft loss (serum creatinine, SCr,
      >5 mg/dl). Of these, two patients died because of septicemia and one had acute
      cortical necrosis. There was evidence of infection in 16 patients (40%). Acute
      rejection was seen in 17 patients (45.8%). The 1-year patient and graft survival
      was 89% and at 3 years 70%. The actuarial graft survival at 5 years was 50%.
      Twelve children discontinued CsA after 1 year post-transplant and five of these
      had graft loss. Graft losses were significantly greater in patients who
      discontinued CsA as compared to those who continued CsA (5/12 vs 2/22). After a
      mean follow-up of 31.5+/-3.5 months, of the 37 patients, 10 had graft loss and
      chronic graft dysfunction was observed in another 9 patients. The rest of the 17
      (48%) patients had a mean SCr of 1.2 mg/dl. The long-term outcome of pediatric
      renal transplants in our country remains suboptimal. CsA discontinuation due to
      financial constraints and/or non-compliance remain the most important reasons for
      this.

PMID- 14648339
TI  - Enalapril dosage in steroid-resistant nephrotic syndrome.
AB  - We have examined, in a randomized crossover trial, the antiproteinuric effect of
      treatment with low- (0.2 mg/kg daily) and high-dose (0.6 mg/kg daily) enalapril
      in 25 consecutive patients with steroid-resistant nephrotic syndrome (SRNS).
      Patients in group A ( n=11) received enalapril at low doses for 8 weeks, followed
      by 2 weeks of washout and then at high doses for 8 weeks. Those in group B (
      n=14) initially received enalapril at high and then low doses. Patients continued
      to receive treatment with tapering doses of prednisolone; none received
      concomitant therapy with daily oral or intravenous steroids, alkylating agents,
      cyclosporine, non-steroidal anti-inflammatory drugs, and other antihypertensive
      medications. The urine albumin-to-creatinine (Ua/Uc) ratio and the percentage
      reduction were determined for each phase of therapy. Baseline clinical,
      biochemical, and histological features were comparable in the two groups. In the
      first phase, treatment with low-dose enalapril (group A) resulted in median 34.8%
      Ua/Uc reduction compared with 62.9% with high doses (group B) ( P<0.01). High
      dose enalapril was associated with a significant reduction in Ua/Uc ratio in both
      groups. The combined median Ua/Uc (95% confidence interval) reduction in the low
      dose phase was 33% (-10.3% to 72.4%) and in the high-dose 52% (15.4%-70.4%) (
      P<0.05). The median Ua/Uc ratio at the end of 20 weeks was 1.1 and 1.8 in groups
      A and B, respectively ( P>0.05). Systolic and diastolic blood pressure reductions
      were similar in both groups. No period or carry-over effect was found. Prolonged
      treatment with enalapril thus resulted in a dose-related reduction in nephrotic
      range proteinuria. Titration of the dose of enalapril may be a useful strategy
      for achieving substantial reduction of proteinuria in children with SRNS.

PMID- 14648340
TI  - Antibody response to influenza A vaccination in children with nephrotic syndrome.
AB  - The aim of this study was to determine the antibody response to influenza
      vaccination in children with nephrotic syndrome (NS). Nineteen children with NS
      and 10 healthy controls were vaccinated with a 1999-2000 influenza vaccine. A
      dose of 0.25 ml was used for those under 6 years and 0.5 ml for those over 6
      years. All children were given two doses with a month between each dose. Antibody
      titers were measured before vaccination and 1 month after vaccination in both
      groups and 6 months after vaccination in 8 patients with NS. The proportion of
      subjects in the nephrotic group with protective antibody titers before
      immunization (10.5%) was significantly lower than the proportion at 1 (78.9%) and
      6 months (87.5%) post vaccination. The mean concentration of specific IgG
      antibodies to influenza A in the NS group increased 6-fold at 1 month and
      approximately 14-fold at 6 months. These results suggest that pediatric patients
      with NS have an adequate antibody response to influenza A vaccine. Protective
      antibody titers to influenza A were maintained at 6 months after immunization in
      8 patients with NS.

PMID- 14648341
TI  - Can a congenital dysfunctional bladder be diagnosed from a smile? The Ochoa
      syndrome updated.
AB  - During the last 40 years over 100 patients have been reported with a
      dysfunctional lower urinary tract associated with a peculiar distortion of the
      facial expression. This most unusual disorder was initially considered a local
      observation. Time, however, has proven otherwise, since patients with this
      syndrome have now been reported from various countries throughout the world. This
      association of lower urinary tract and bowel dysfunction with an abnormal facial
      expression was named the urofacial (Ochoa) syndrome. Genetic studies have
      demonstrated that this condition is inherited as an autosomal recessive trait,
      and a potential gene has been mapped to chromosome 10q23-q24. There is also
      enough evidence to suggest that patients with this syndrome as well as those with
      subclinical neurological bladder, occult neuropathic bladder, non-neurogenic
      neurogenic bladder or Hinman syndrome, dysfunctional voiding, or dysfunctional
      elimination may be affected by the same congenital disorder of neurological
      origin.

PMID- 14648342
TI  - Captopril scintigraphy in the study of arterial hypertension in pediatrics.
AB  - Renovascular hypertension (RVH) is responsible for 10% of arterial hypertension
      in children. The early diagnosis of RVH permits specific treatment leading to the
      cure of hypertension and avoidance of parenchymal damage. Captopril renal
      scintigraphy (CRS) provides information on the renovascular cause of the arterial
      hypertension. To validate the usefulness of CRS in hypertensive children,
      clinical, scintigraphic, and radiological data from 20 patients (mean age 6.1+/
      5.5 years) were reviewed. Two patients were newborns. All had renal ultrasound
      scans and 9 had aortograms. In 7 children, RVH was confirmed by angiography, and
      CRS was positive for RVH in 6 of these. CRS was negative for RVH in 12 of 13
      children without RVH. CRS was non-diagnostic in 3 children with abnormal baseline
      renal scintigraphy and severely decreased relative renal function ( <35%), 1 of
      whom had RVH. No side effects of captopril renography were observed. Captopril
      renography provides a logical, non-invasive, safe, and cost-effective approach in
      the evaluation of children suspected of having RVH.

PMID- 14648343
TI  - A multicenter experience on patient and technique survival in children on chronic
      dialysis.
AB  - In this study we compared patient and technique survival of 163 new hemodialysis
      (HD) patients (age 11.4+/-3.1 years) and 295 peritoneal dialysis patients (7.7+/
      4.8 years. P< 0.001), treated in 23 dialysis centers participating in the Italian
      Registry of Pediatric Chronic Peritoneal Dialysis (CPD) during the years 1989
      2000. Three HD (1.8%) and 17 CPD (5.8%) patients died; the overall average death
      rate was 9.8/1,000 patient-years in HD and 29.8/1,000 patient-years in CPD
      patients. No statistically significant difference in patient survival between CPD
      and HD was found, while the survival of 102 CPD children younger than 5 years at
      the start of dialysis was lower ( P=0.0001) than that of 193 CPD and 160 HD
      patients aged 5-15 years. We registered 12 modality failures among HD (7.4%)
      patients and 44 among CPD (14.9%) patients. The main causes were vascular access
      failure and patient choice in HD, and infection in CPD patients. Technique
      survival was lower ( P=0.007) in CPD than in HD patients; a statistically
      significant difference ( P=0.01) was also observed between both the 0- to 5- and
      the 5- to 15-year-old CPD patients and the HD patients aged 5-15 years. Logistic
      regression analysis confirmed age at initiation of dialysis to be a predictor of
      patient death ( P=0.0001) in the whole patient population, and of technique
      failure in HD ( P=0.006) but not in CPD patients ( P=0.16).

PMID- 14648344
TI  - Fed-batch culture of Bacillus thuringiensis based on motile intensity.
AB  - The operation of a fed-batch culture is more complicated than that of batch or
      continuous culture. Thus, an appropriate feeding strategy for fed-batch cultures
      should be carefully designed. In this study, a simple feeding strategy for fed
      batch culture of Bacillus thuringiensis based on "motile intensity" is described.
      The feeding strategy consisted of two steps: (1) initiating feeding at the peak
      of motile intensity; (2) terminating feeding at low motile intensity (or non
      motility) of the cells. In addition, the motile intensity of B. thuringiensis was
      used to determine the optimum environmental conditions (pH, temperature, and
      dissolved oxygen) and optimum medium composition. Using this fed-batch strategy,
      the production of thuringiensin increased 34% compared with batch culture using
      the same environmental conditions and medium composition. The proposed strategy
      for fed-batch culture helps to avoid overfeeding of substrate and facilitates on
      line control. A comparison of several alternative strategies for fed-batch
      culture demonstrated that strategies such as glucose-stat and DO-stat result in a
      lower productivity than that obtained using the motility intensity method.

PMID- 14648345
TI  - Optimization of a culture medium for ligninolytic enzyme production and synthetic
      dye decolorization using response surface methodology.
AB  - A Box-Wilson central composite design was applied to optimize copper, veratryl
      alcohol and l-asparagine concentrations for Trametes trogii (BAFC 212)
      ligninolytic enzyme production in submerged fermentation. Decolorization of
      different dyes (xylidine, malachite green, and anthraquinone blue) by the
      ligninolytic fluids from the cultures was compared. The addition of copper
      stimulated laccase and glyoxal oxidase production, but this response was
      influenced by the medium N-concentration, with improvement higher at low N
      levels. The medium that supported the highest ligninolytic production (22.75 U/ml
      laccase, 0.34 U/ml manganese peroxidase, and 0.20 U/ml glyoxal oxidase) also
      showed the greatest ability to decolorize the dyes. Only glyoxal oxidase activity
      limited biodecoloration efficiency, suggesting the involvement of peroxidases in
      the process. The addition of 1-hydroxybenzotriazole (a known laccase mediator) to
      the ligninolytic fluids increased both their range and rate of decolorization.
      The cell-free supernatant did not decolorize xylidine, poly R-478, azure B, and
      malachite green as efficiently as the whole broth, but results were similar in
      the case of indigo carmine and remazol brilliant blue R. This indicates that the
      mycelial biomass may supply other intracellular or mycelial-bound enzymes, or
      factors necessary for the catalytic cycle of the enzymes. It also implies that
      this fungus implements different strategies to degrade dyes with diverse chemical
      structures.

PMID- 14648346
TI  - [A brain tissue bank in a neuropathology laboratory. Basic methodology].
AB  - The Meixoeiro Hospital Brain Bank (BB) was established at the end of 2002. A BB
      is a tissue collection and storage system, established under the best conditions
      to carry out prospective morphological, biochemical or molecular studies. The BB
      should ideally be supported by a donor program, although samples may also be
      obtained from autopsy material from patients with neurodegenerative diseases.
      Recruitment of control cases from brains without neurological diseases is basic.
      The main goal of a BB is to provide brain tissue for research. Each case requires
      accurate clinical data, a definite diagnosis and optimal conditions of tissue
      preservation. The use of protocols to standardize the handling and processing of
      tissues, data recruitment and neuropathological diagnosis is fundamental to
      assure the quality and homogeneity of samples. Close collaboration between
      neuropathologists, neurologists and other specialists is essential in all the
      process. Although important advances in the tissue banking field have been
      achieved, the number of donors in Spain still remains low. Stronger institutional
      support as well as public awareness through better diffusion of the information
      is necessary to increase the number of donors and improve BB development.

PMID- 14648347
TI  - [Cognitive and functional decline in the stage previous to the diagnosis of
      Alzheimers disease].
AB  - INTRODUCTION: The decline in the phase prior to diagnosis of Alzheimers disease
      (AD) is not well known, although this knowledge is necessary to evaluate the
      efficiency of new drugs that can influence in disease course prior to diagnosis.
      OBJECTIVE: To contribute to better knowledge of the decline prior to diagnosis,
      we have investigated the cognitive and functional deterioration for 2-3 years
      before the probable AD diagnosis was established. PATIENTS AND METHODS: We
      compared results obtained by 17 control subjects and 27 patients at the time of
      diagnosis of a probable AD with results obtained 2-3 years before (interval of
      27.7 4 months). We compared memory functions (logical, recognition, learning and
      autobiographical memory), naming, visual and visuospatial gnosis,
      visuoconstructive praxis, verbal fluency and the Mini-Mental State Examination
      (MMSE), Informant Questionnaire and Blessed's Scale scores. RESULTS: Performance
      of control subjects did not change. AD patients showed a significant decline in
      scores, except for verbal fluency. In order of importance, cognitive decline was
      more marked in scores of learning memory, visuospatial gnosis, autobiographical
      memory and visuoconstructive praxis. CONCLUSIONS: Decline prior to diagnosis of
      AD is characterized by an important learning memory impairment. Deterioration of
      visuospatial gnosis and visuoconstructive praxis is greater than deterioration of
      MMSE and Informant Questionnaire scores.

PMID- 14648348
TI  - A clinical longitudinal study of multiple sclerosis in Cantabria, Spain.
AB  - INTRODUCTION: There are many studies that analyze the clinical course of multiple
      sclerosis (MS), but only a few of them observed patients from their first
      episode. We report a MS series of patients longitudinally evaluated from the
      onset of the disease and compare outcome between immunosuppressive treatment and
      non-treatment groups. PATIENTS AND METHODS: Patients were included when their
      follow-up was at least three years and serial examination was available. Poser's
      criteria were used for diagnosis. We measured neurological impairment according
      to Kurtzke's expanded disability status scale (EDSS). RESULTS: Fifty-five MS
      patients were followed-up. Forty-six had clinically defined and nine clinically
      probable MS. Thirty-three patients had relapsing-remitting, 11 had secondary
      progressive and 11 had primary-progressive MS. Mean age of onset of the disease
      was 31.1 years and mean duration of follow-up was seven years. Pyramidal weakness
      and sensory symptoms were the most common initial manifestations. Median time to
      reach EDSS-3 and EDSS-6 from onset was 4.5 and 7.5 years, respectively. From a
      total of 23 patients with follow-up of 10 or more years, 11 (48 %) had benign MS.
      The average time from onset of MS to secondary-progressive was 6.1 years. There
      were no significant differences between treatment and non-treatment patients.
      CONCLUSION: Longitudinal studies starting from early clinical course of MS are
      most useful in determining its semeiology, clinical pattern and outcome. Our
      results call for caution in initiating early immunosuppressive or
      immunomodulatory therapy.

PMID- 14648349
TI  - [Arterial hypertension and intracerebral hemorrhage].
AB  - Intracerebral hemorrhage (ICH) is still a devastating stroke, with high
      mortality. Arterial hypertension (AHT) is the most common cause of primary ICH,
      causing changes in the wall of small vessels, leading to its rupture. Recent
      studies have attempted to understand the basic mechanisms of tissue damage around
      the hematoma. These days there is a debate regarding biochemical changes in this
      area, usually recognized as edema. Detection with the gradient-echo T2 weighted
      MRI of old and silent microhemorrhages in a patient with ICH as a radiological
      expression of a microangiopathy of small vessel poses questions regarding its
      predictive value of risk of bleeding recurrence. The object of our review is to
      analyze the present data that explains the interaction between chronic
      hypertension and primary ICH.

PMID- 14648350
TI  - [Painful ophtalmoparesis: benefits of the radiological study].

PMID- 14648351
TI  - [HIV related Foix-Chavany-Marie syndrome].
AB  - Automatic-voluntary motor dissociation of the face and lower cranial nerves of
      brainstem is the hallmark of Foix-Chavany-Marie syndrome (biopercular syndrome).
      It is commonly caused by ischemic strokes. We present a biopercular syndrome
      associated with HIV. A 41 year old female who presents a progressive automatic-
      voluntary motor dissociation of face and lower cranial nerves with later
      involvement of limbs. She was immunodepressed as a result of HIV. MRI showed
      bilateral lesions in opercular areas and ventrolateral thalamic nucleus, likely
      as a result of retrograde neuronal degeneration. Automatic-voluntary dissociation
      occur after biopercular lesions with sparing of motor pathway proceeding from the
      cingulate cortex.

PMID- 14648352
TI  - [Spontaneous closure of a intracraneal dural arteriovenous fistula by controlled
      hypotension during a general anesthesia procedure. A case report].
AB  - Intracranial dural arteriovenous fistulas (DAVF) are arteriovenous communications
      within the duramater, which seem to be pathophysiologically related to a venous
      sinus thrombosis. DAVF may require invasive treatment, although rarely
      spontaneous occlusion has been reported. The present case is a 48-year-old male
      with a diagnosed type III DAVF of the right lateral sinus. Complete endovascular
      embolization was not possible to perform, so he was considered a candidate for
      surgical treatment. During perioperative management, under general anesthesia,
      the intraoperative arteriographyc monitoritation showed a spontaneous closure of
      the DAVF after induced controlled hypotension, resulting in complete cure. We
      conclude that controlled hypotension could become an alternative for treatment of
      DAVF in high risk patients or when there is no chance for embolization.patients
      or when there is no chance for embolization. Neurologia 2003;18(10):746-749

PMID- 14648353
TI  - [Eales' disease with bilateral brain strokes and jaw-closing dystonia].
AB  - Eales' disease is an idiopathic occlusive vasculopathy of the retina, which is
      characterized by extensive peripheral non-perfusion, perivascular sheathing, and
      neovascularization. It is associated with recurrent vitreous hemorrhages. Both
      eyes are affected consecutively in 80% to 90% of the patients. In spite of the
      multiple theories that have been proposed, it continues to have unknown origin
      and its diagnosis relies on exclusion of other causes of retinal vasculopathy. In
      some occasions, these patients develop complications of the central nervous
      system, above all brain infarcts. We present the case of a 38 year old woman with
      Eales' disease who developed bilateral brain infarcts associated with occlusion
      or stenosis of the middle cerebral arteries. The cerebral angiography showed
      beading of the Silvian arteries, suggestive of an underlying inflammatory
      disorder. Early corticosteroid therapy could avoid contralateral retinal
      involvement and neurological complications. The patient also presented delayed
      jaw closing dystonia secondary to basal ganglia infarct which followed a benign
      course with spontaneous resolution in a few days.

PMID- 14648354
TI  - [X-ray contributions to the Opalski syndrome].

PMID- 14648355
TI  - [Bilateral occipital intraparenchymatous bleeding?].

PMID- 14648356
TI  - Comparison of Calidria chrysotile asbestos to pure tremolite: inhalation
      biopersistence and histopathology following short-term exposure.
AB  - The differences between chrysotile asbestos, a serpentine mineral, and amphibole
      asbestos have been debated extensively. Many studies have shown that chrysotile
      is cleared from the lung more rapidly than amphibole. In order to quantify the
      comparative clearance of chrysotile and the amphibole asbestos tremolite, both
      fibers were evaluated in an inhalation biopersistence study that followed the
      European Commission recommended guidelines. In addition, the histopathological
      response in the lung was evaluated following the short-term exposure. This
      article presents the results of this study through 90 days after cessation of
      exposure. Following the termination of the study, a subsequent article will
      provide the complete results through 12 mo after cessation of exposure. In order
      to quantify the dynamics and rate by which these fibers are removed from the
      lung, the biopersistence of a sample of commercial grade chrysotile from the
      Coalinga mine in New Idria, CA, of the type Calidria RG144 and of a long-fiber
      tremolite were studied. For synthetic vitreous fibers, the biopersistence of the
      fibers longer than 20 microm has been found to be directly related to their
      potential to cause disease. This study was designed to determine lung clearance
      (biopersistence) and the histopathological response. As the long fibers have been
      shown to have the greatest potential for pathogenicity, the aerosol generation
      technique was designed to maximize the number of long respirable fibers. The
      chrysotile samples were specifically chosen to have 200 fibers/cm3 longer than 20
      microm in length present in the exposure aerosol. These longer fibers were found
      to be largely composed of multiple shorter fibrils. The tremolite samples were
      chosen to have 100 fibers/cm3 longer than 20 microm in length present in the
      exposure aerosol. Calidria chrysotile fibers clear from the lung more rapidly
      (T1/2, fibers L > 20 microm = 7 h) than any other commercial fiber tested
      including synthetic vitreous fibers. With such rapidly clearing fibers, the 5-day
      exposure would not be expected to result in any pathological change in the lung,
      and the lungs of animals that inhaled Calidria chrysotile showed no sign of
      inflammation or pathology and were no different than the lungs of those animals
      that breathed filtered air. Following this 5-day exposure to tremolite, the
      tremolite fibers once deposited in the lung parenchyma do not clear and almost
      immediately result in inflammation and a pathological response in the lung. At
      the first time point examined, 1 day after cessation of exposure, inflammation
      was observed and granulomas were already formed. By 14 days postexposure these
      microgranulomas had turned fibrotic, and by 90 days postexposure the severity of
      the collagen deposits had increased and interstitial fibrosis was observed in one
      of the rats. These findings provide an important basis for substantiating both
      kinetically and pathologically the differences between chrysotile and the
      amphibole tremolite. As Calidria chrysotile has been certified to have no
      tremolite fiber, the results of the current study together with the results from
      toxicological and epidemiological studies indicate that this fiber is not
      associated with lung disease.

PMID- 14648357
TI  - Pulmonary effects and clearance after long-term inhalation of potassium
      octatitanate whiskers in rats.
AB  - The pulmonary effects of long-term inhalation of potassium octatitanate whisker
      (PT1), one of the durable man-made fibers (MMFs), were examined in rats. Male
      Wistar rats were exposed to PT1 by inhalation for 6 h/day, 5 days/wk for 1 yr.
      The daily average exposure concentration of PT1 aerosol was 2.2 +/- 0.7 mg/m3
      (111 +/- 34 fiber/ml) during the exposure. Rats were sacrificed at 3 days, 6 mo,
      and 12 mo after 1 yr of inhalation exposure. The amount of deposited PT1 in rat
      lungs (lung burden) was 2.4 +/- 0.7 mg and the deposition fraction was 7.2% at 3
      days after 1 yr. The clearance of inhaled PT1 after 1-yr inhalation was prolonged
      so that the biological half-life time (BHT) was difficult to estimate. The
      histopathological findings showed that mild fibrotic changes were observed around
      the macrophages that had engulfed the PT1 in the 3-day, 6-mo, and 12-mo rat
      sacrifice groups. As for pulmonary tumors, no malignant tumors were observed,
      although 2 adenomas at 6 mo and 1 adenoma and 1 squamous metaplasia at 12 mo
      after the exposure were found in the rat lungs.

PMID- 14648358
TI  - A distributed-parameter model for formaldehyde uptake and disposition in the rat
      nasal lining.
AB  - DNA-protein cross-links (DPX) serve as a dosimeter for inhaled formaldehyde and
      are associated with tumor induction in rat nasal passages after chronic exposure
      to 6 ppm and above. To determine the role of epithelium-specific morphometry in
      formaldehyde-induced patterns of injury, we developed a mathematical model that
      links airflow-driven formaldehyde uptake with DPX formation in regions of the rat
      nose with high and low tumor incidence. A three-dimensional, anatomically
      accurate computational fluid dynamics model of rat nasal airflow and inhaled gas
      uptake was integrated with a physiologically based mathematical model
      incorporating tissue thickness, formaldehyde diffusion, its removal by enzymatic
      and nonenzymatic processes, and DNA distribution in the nasal mucosa to predict
      DPX formation. The model implicitly incorporates the reversible conversion of
      formaldehyde to methylene glycol. Where possible, parameter values were taken
      from the literature or estimated using published correlations. The Michaelis
      Menten kinetic constants Vmax and Km, as well as a first-order constant for
      formaldehyde removal, were left as fitted parameters. The resultant model fit to
      the experimentally measured DPX in the high- and low-tumor-incidence regions of
      the rat nasal passages was very good. Sensitivity analysis indicates that among
      the fitted parameters, model fits are most sensitive to Vmax and that predictions
      were sensitive to changes in tissue thickness when all other parameters are held
      constant. The model structure facilitates extrapolation to primates and humans
      and application to other soluble, reactive gases.

PMID- 14648359
TI  - Exposure to concentrated ambient air particles alters hematologic indices in
      humans.
AB  - Descriptions of changes in hematological indices have contested the premise that
      the biological effects of suspended particulate matter (PM) are restricted to the
      lung. Employing approximately 40 hematologic parameters reflecting blood cells,
      chemistries, mediators, and coagulation factors, we tested the hypothesis that
      exposure to concentrated ambient air particles (CAPs) can be associated with
      changes in hematologic indices in normal humans. Twenty healthy young volunteers
      were exposed to either filtered air (n = 5) or CAPs (n = 15) with a mean PM mass
      of 120.5 +/- 14.0 microg/m3 and a range from 15.0-357.6 microg/m3. Hematologic
      indices were measured. Changes in all parameters are expressed as the absolute
      value either immediately after or 24 h after exposure. Differences between
      responses of those individuals exposed to filtered air and CAPs were tested using
      the T-test of independent means. If significant differences between the two
      groups were suggested by the T-test (p < .10), the relationship was further
      evaluated employing linear regression techniques. Regression analysis verified
      significant linear relationships between particle mass the individual was exposed
      to and (1) decrements in WBC count 24 h later, (2) decreases in lactate
      dehydrogenase (LDH) concentration 24 h later, and (3) elevations in fibrinogen
      levels 24 h later. There were no changes in either inflammatory mediators in the
      blood or indices of coagulation/fibrinolysis other than fibrinogen. We conclude
      that exposure of healthy volunteers to CAPs can be associated with decreases of
      both white blood cell (WBC) count and LDH and increased concentrations of
      fibrinogen in the blood.

PMID- 14648360
TI  - Respiratory diseases in French cork workers.
AB  - A cross-sectional study on suberosis was conducted in the Champagne-Ardenne
      County, France, to determine the prevalence of respiratory symptoms, the level of
      pulmonary function, and the presence of precipitins against Penicillium
      frequentans. Thirteen of the 33 workers exposed to cork dust had respiratory
      symptoms excluding hypersensitivity pneumonitis. The respiratory symptoms were
      not correlated with tobacco habits or duration of exposure. The levels of
      pulmonary function were not significantly impaired. No precipitin arc against
      Penicillium frequentans was found in the sera of exposed workers. The varied
      symptomatology of suberosis may point to several different diseases, each with
      its own determining factor. In the present study, exposure to weak humidity and
      low level of cork dust were related to asthma and chronic bronchitis only,
      excluding hypersensitivity pneumonitis.

PMID- 14648361
TI  - [Importance of epidemiology in ophthalmology].

PMID- 14648362
TI  - [Retinal regeneration from bone marrow-derived stem cells].

PMID- 14648363
TI  - [Spanish articles published in ophthalmology journals].

PMID- 14648364
TI  - The Madrid triple classification of dry eye.
AB  - From the clinical point of view, there are many etiologic causes, several
      combinations of anatomo-pathologic manifestations, and different grades of
      severity of Dry Eye diseases in the dysfunctional tear film syndrome. The
      dacryologist doctor must recognize these three parameters, quantify them, and
      establish the most appropriate treatment. The present triple classification has
      been elaborated for this purpose. First, there is an etiologic distribution in
      ten groups: age-related, hormonal, pharmacologic, immunopathic, hyponutritional,
      dysgenetic, inflammatory, traumatic, neurodeprivative, and tantalic. Each of
      these groups comprise many variants. Second, there is an anatomo-pathologic
      classification named ALMEN classification from the acronym of aquodeficiency,
      lipodeficiency, mucodeficiency, epitheliopathy, and non-ocular exocrine
      affectations. Finally, there is a severity classification in five grades:
      subclinical (symptoms only when overexposure), mild (habitual symptoms), moderate
      (symptoms plus reversible signs), severe (symptoms plus permanent signs), and
      disabling (all the above, plus visual discapacity).

PMID- 14648366
TI  - [Surgical arteriovenous decompression (sheathotomy) in branch retinal vein
      occlusion: retrospective study].
AB  - PURPOSE: To evaluate best-corrected visual acuity (BCVA), incidence of
      neovascularization and angiographic changes in patients with branch retinal vein
      occlusion (BRVO) treated with surgical decompression by sheathotomy. METHODS:
      Retrospective study including 17 cases of temporal BRVO with macular edema
      treated with surgical decompression. Results of BCVA, incidence of
      neovascularization and vitreous hemorrhage 6 months following surgery are
      included. Angiographic changes in the first 8 cases a month after decompression
      are also evaluated. RESULTS: The mean postoperatory BCVA was 0.40 with a mean
      improvement of 0.26. Seventy one percent of patients (12/17) improved 2 or more
      visual acuity lines and 53% of patients (9/17) improved 4 or more lines. Only in
      one case the vision worsened. There was no evidence of retinal neovascularization
      or rubeosis iridis six months after surgery. CONCLUSIONS: Surgical decompression
      is a therapeutical option for those patients suffering BRVO with macular edema.
      Our initial results are encouraging, not only regarding visual acuity
      improvement, but also because of a decreased risk of neovascularization. No
      patient included in our study developed neovascularization.

PMID- 14648367
TI  - [White-on-white, blue-on-yellow and blue-on-blue perimetry in normal subjects].
AB  - PURPOSE: To compare blue-on-blue differential contrast perimetry (BB), in
      accordance with E. Land "Retinex" theory, with white-on-white (WW) and blue-on
      yellow (BY) perimetries on normal subjects. METHODS: An Octopus 101 perimeter was
      modified for BB perimetry, using a 4cd/m2 background and stimulus Goldmann size
      V. Fifty healthy subjects (10 per decade, from 20 to 70 years) were examined
      twice with each type of perimetry (WW, BB, BY) using the TOP strategy. RESULTS:
      The results obtained with WW, BY and BB perimetry were respectively: Reduction of
      sensitivity per year: 0.13, 0.27 and 0.13 dB; correlation coefficient (r) of
      threshold with age (and error of estimation of Y over X): -0.63 (2.24 dB), -0.70
      (3.77 dB) and -0.80 (1.32 dB); threshold fluctuation: 2.21, 3.03 and 2.03 dB;
      percentage of points deviated more than 5dB from the expected value for the
      patient age: 8.1, 16.0 and 4.2%. CONCLUSIONS: Perimetric results are more stable
      with BB strategy than with the other two types of perimetry. BY perimetry gives
      the worst results: threshold reduction with age is twice higher, individual
      fluctuation is 50% higher and points away from the mean value are much more
      frequent. Overlapping between blue and yellow filters is minimal in Octopus.
      Therefore, an absolute threshold is examined, which is much more unstable than WW
      or BB differential thresholds.

PMID- 14648368
TI  - [Impression cytology study of dry eyes in patients with congenital aniridia].
AB  - PURPOSE: To evaluate the long-term results of ocular surface reconstruction by
      means of medical treatment, limbal transplantation or amniotic membrane
      transplantation in patients with congenital aniridia. MATERIAL AND METHODS:
      Thirty-six eyes from 18 consecutive patients with aniridia were studied by
      clinical tests (Schirmer test, break-up time and vital rose bengal staining) and
      impression cytology. Thirteen patients were treated with lubricant drops for
      ocular dryness. Two eyes from 2 patients also received limbal transplantation,
      and other 4 eyes underwent amniotic membrane transplantation. RESULTS: Corneal
      and conjunctival epithelium improved in all patients treated with lubricant
      drops. Ocular surface epithelium condition was worse in those patients not
      receiving artificial tears. After 12 months of limbal transplantation, clinical
      and morphological results showed a significant corneal recovery of at least two
      grades of squamous metaplasia in comparison with the previous situation. We also
      carried out amniotic membrane transplantation in patients with aniridia. The
      improvement was initially observed after 2 months and by the sixth month there
      was a significant improvement in clinical signs and symptoms, with normal corneal
      cells next to altered ones. CONCLUSIONS: All the aniridic patients showed dry
      eye. Treatment with lubricant drops is necessary to decrease the squamous
      metaplasia process. Limbal transplantation and amniotic membrane implantation are
      needed for effective corneal surface reconstruction in patients with aniridia,
      which is followed by a significant improvement of the dry eye.

PMID- 14648369
TI  - [Interferon alpha and infantile orbital hemangioma].
AB  - OBJECTIVE: To determine the efficacy and safety of interferon alpha therapy for
      the treatment of infantile periorbital hemangiomas associated with visual
      impairment. METHODS: Retrospective study of 4 patients diagnosed of orbital
      hemangioma during infancy. All of them were treated with interferon alpha 2b at
      doses of 3 million U/m2, administered once daily by subcutaneous injection, at
      least during 3.5 months. The lesions were compared through clinical evaluation
      and diagnostic imaging (echography, CT and MRI) before, during and after
      treatment, estimating the percentage of lesion reduction in relation to the
      initial size. RESULTS: In 3 cases, a 95% volume reduction was detected, and
      greater than 50% in the other one. Spastic diplegia was detected in a child
      during treatment, but resolved without persistent neurological deficits when
      discontinued. Alterations in plasmatic lipid profile were detected in one
      patient. CONCLUSION: Interferon alpha can be a valuable treatment for periorbital
      hemangiomas of infancy; even though, adverse effects can be clinically
      significant.

PMID- 14648370
TI  - [Strabismus surgery of the myopic patient under topical anaesthesia].
AB  - PURPOSE: To study the epidemiological characteristics and the results of
      strabismus surgery of high myopic patients under topical anaesthesia. METHOD:
      Retrospective study of nine high myopic patients with restrictive myopic myopathy
      (RMM) that underwent surgery in the last year and with a minimum follow-up of at
      least 6 months following surgery. Clinical findings, alteration of the extrinsic
      ocular motility (EOM) and response to surgical treatment were evaluated in each
      case. RESULTS: RMM was more frequent in women, average age was 46 years and
      average refractive error was 14 diopters. Diplopia was the most frequent reason
      for consultation, followed by the wish to undergo surgery because of an
      aesthetically unacceptable strabismus. High myopia was the most frequent
      etiology. One case was secondary to decompensated fourth cranial nerve palsy. The
      alteration of the EOM more frequently observed was endotropia associated with
      hypotropia. The recurrence rate of the deviation was 44%, occurring generally in
      the immediate postoperative period. In these cases botulinum toxin is a valid
      treatment option. CONCLUSIONS: Topical anaesthesia offers undoubted advantages
      for a better adjustment of diplopia in RMM surgery. During the intraoperative
      adjustment it is convenient to overcorrect the horizontal deviation and to
      undercorrect the vertical deviation.

PMID- 14648372
TI  - [Monophthalmia of the painter Giuseppe Abbati (1836-1868)].

PMID- 14648374
TI  - [G-DRGs - Quo vadis?].

PMID- 14648375
TI  - HFE genotype and parameters of iron metabolism in German first-time blood donors 
      evidence for an increased transferrin saturation in C282Y heterozygotes.
AB  - BACKGROUND: Hemochromatosis is usually inherited in an autosomal recessive mode
      and associated with missense mutations in the hemochromatosis gene (HFE), an HLA
      class 1 related gene. However the degree of penetrance is presently matter of
      debate. METHODS: To elucidate the frequency of HFE mutations in a German
      population and the relationship between genotype and phenotype, we determined the
      HFE C282Y and H63D genotypes in 500 first-time blood donors using an allele
      specific ligase chain reaction (LCR). Ferritin and transferrin saturation (TS) of
      all donors found to have at least one mutation were compared to gender- and age
      matched controls. RESULTS: The C282Y allele frequency was 46 in 1000 chromosomes
      (4.6 %). The allele frequency of H63D was 108 in 1000 (10.8 %) chromosomes. We
      found three persons homozygous for H63D, nine compound heterozygotes and none
      homozygous for C282Y. TS was elevated in C282Y heterozygotes (p = 0.002) and
      C282Y/H63D compound heterozygotes (p = 0.04) compared to wild-type controls.
      Serum ferritin tended to be elevated in compound heterozygotes (p = 0.053). Mean
      corpuscular volume (MCV) and hemoglobin (MCH) were not different from controls.
      CONCLUSION: The frequency of HFE mutations in the tested population was
      comparable to those of other northern European populations. The elevated TS in
      subjects carrying a single copy of the C282Y mutation suggests that C282Y
      heterozygosity is associated with an increased intestinal iron absorption and
      might therefore offer a selection advantage in conditions of iron depletion.

PMID- 14648376
TI  - [Screening colonoscopy among persons 50 to 60 years of age with and without
      familial risk of colorectal cancer - a prospective multicenter trial].
AB  - BACKGROUND: In Germany screening colonoscopy was introduced into the National
      program on colorectal cancer prevention in Oktober 2002. The prevalence of
      neoplasia in patients with and without familiar risk was determined together with
      patient satisfaction with screening colonoscopy. METHODS: Asymptomatic subjects
      from 50 to 60 years underwent screening colonoscopy and were stratified in two
      groups with and without familiar risk (first-degree relatives with CRC) in a
      multicenter trial among German gastroenterologists. Advanced neoplasia was
      defined as an adenoma at least 1 cm in diameter, a villous adenoma, an adenoma
      with high-grade dysplasia, or invasive cancer. After recovery from sedation all
      subjects were asked if they would agree to a control colonoscopy and the pain
      score was recorded on a scale from 0 to 6. RESULTS: A total of 557 subjects (322
      at average risk and 235 with familiar risk) underwent screening colonoscopy. The
      prevalence of advanced neoplasia in subjects without/with familiar risk was not
      significantly different in persons from 50 to 54 years (9 vs. 15 %) in contrast
      to persons from 55 to 60 years (10 vs. 22 %, p = 0.004) where the relative risk
      was doubled. Compared to younger patients, the prevalence of all neoplasia
      (including small adenomas) was significantly different only for older patients
      with familiar risk (44 vs. 23 %, p < 0.0001). The mean value of the pain-score
      was 0.76 + 1.0. Subjects examined without medication had significantly higher
      pain scores than subjects under medication. Colonoscopy performed under
      disoprivan resulted in similar pain-scores compared to midazolam at dosages > 5
      mg. All patients agreed to a control colonoscopy. CONCLUSION: Screening
      colonoscopy is an effective and well-accepted method. The high prevalence of
      advanced neoplasia even in persons from 50 to 54 years suggests that screening
      should start at the age of 50.

PMID- 14648377
TI  - Fulminant liver failure induced by hepatosplenic alphabeta T-cell lymphoma.
AB  - Since survival rates of fulminant liver failure are low, early consideration of
      liver transplantation in patients developing hepatic encephalopathy due to
      progressive liver failure is mandatory. Rapid diagnostic work-up is necessary to
      identify the underlying disease and to rule out contraindications to liver
      transplantation. We report the case of a 35-year-old patient presenting with
      fulminant hepatitis and a four-week history of biopsy-proven autoimmune
      hepatitis. Despite high-dose steroid-treatment liver function progressively
      worsened and hepatic encephalopathy rapidly developed. Histopathologic evaluation
      of a liver biopsy specimen revealed necrotizing hepatitis and rare atypical
      lymphocytes. Surgical biopsy specimens confirmed the suspicion of an aggressive
      hepatosplenic alphabeta T-cell lymphoma which represents a contraindication to
      liver transplantation.

PMID- 14648378
TI  - Treatment of pouchitis with dehydroepiandrosterone (DHEA) - a case report.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) inhibits activation of nuclear factor
      kappa B (NF-kappaB), which is known to be activated in inflammatory lesions of
      ulcerative colitis, via PPARalpha. In a pilot trial DHEA was effective for the
      treatment of active ulcerative colitis. Pouchitis is a common complication after
      proctocolectomy for ulcerative colitis and still a therapeutical challenge. CASE:
      DHEA 200 mg/d was tested in chronic active pouchitis in a 35-year-old female
      patient. DHEA was given for eight weeks, and follow up for further eight weeks
      was performed. The number of stools dropped from 15-18/d to 8/d, the addition of
      mucus, which was observed initially, was absent during treatment. The consistence
      of stools improved from liquid/soft to soft/solid. Abdominal pain resolved and
      endoscopical signs of inflammation improved. Eight weeks after termination of
      treatment with DHEA, the patient again suffered from 12 to 18 soft to liquid
      stools per day and mild abdominal pain. CONCLUSION: Therapeutic effects of DHEA
      in pouchitis should be evaluated systematically.

PMID- 14648379
TI  - [Gastroenterology in the G-DRG-System 2004].
AB  - After a year of preliminary voluntarily introduction of casemix funding in
      hospitals in 2003 nearly every German hospital will be confronted with lump sump
      payments on the basis of the G-DRG system for their inpatient care starting from
      January 2004. To analyse weaknesses referring to gastroenterology services within
      the G-DRG version 1.0 the German Association for Disorders of the Digestive
      System and Metabolism (DGVS) and the DRG-Research-Group from the University of
      Muenster conducted a DRG evaluation project. In the analysis patient data from 16
      hospitals were included. As a result of the project recommendations for G-DRG
      adjustments were generated. Those recommendations were implemented in the
      advancement to G-DRG version 2004. Also the International Classification of
      Diseases (ICD-10) was modified to ICD-10 German Modification. The classification
      of procedures OPS-301 was revised. The main adjustments to the G-DRG system and
      both classifications will be presented in this paper.

PMID- 14648380
TI  - Immunobiology and gene-based immunotherapy of hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is one of the major malignancies
      worldwide. For most patients with advanced or multifocal HCC treatment options
      are limited resulting in a poor prognosis. Several local ablation methods have
      been developed as minimally invasive strategies for HCC treatment. It is unclear,
      until now, whether these therapies will significantly improve the poor prognosis
      of patients with unresectable HCC. Novel therapeutic strategies and a better
      understanding of HCC imunobiology are, therefore, urgently required. DESIGN: The
      scientific literature since 1970 in all languages cited in Medline was
      systematically reviewed. RESULTS: Until now, a variety of specific and non
      specific immunostimulatory strategies against HCC has been applied in preclinical
      experimental models with some promising results. The molecular characterization
      of HCC associated tumour antigens such as alpha-fetoprotein (AFP) and the
      increased understanding of the immunological pathways involved in liver and tumor
      immunology have paved the way for the design of promising gene-based cancer
      vaccines. The first phase I and II immunotherapeutic clinical trials based on
      dendritic cell immunotherapy and peptide vaccines are ongoing in HCC-patients.
      Clinical trials have, in general, demonstrated the safety of such strategies.
      Recently, exciting new immunological techniques and tools have been developed
      which allow to characterize antigen specific T cells at a single-cell level. In
      future, HCC specific tumor rejection antigens which can be used therapeutically
      have to be identified using microarray-based analysis. The different therapeutic
      modalities need to be compared directly resulting in optimised therapeutic
      approaches and the identification of sub-groups of HCC-patients responding
      favourably to treatment.

PMID- 14648381
TI  - [Protection against obesity and insulin resistance in dipeptidylpeptidase-IV
      knock-out-mice].

PMID- 14648382
TI  - [Adhesions to explain abdominal complaints: a concept to adhere to?].

PMID- 14648383
TI  - [Therapy in patients with Barrett's Esophagus].

PMID- 14648385
TI  - ["Mirror, mirror on the wall which is the best proton pump inhibitor of all?"].

PMID- 14648389
TI  - Natural modulators of large-conductance calcium-activated potassium channels.
AB  - Large-conductance calcium-activated potassium channels, also known as BK or Maxi
      K channels, occur in many types of cell, including neurons and myocytes, where
      they play an essential role in the regulation of cell excitability and function.
      These properties open a possible role for BK-activators (also called BK-openers)
      and/or BK-blockers as effective therapeutic agents for different neurological,
      urological, respiratory and cardiovascular diseases. The synthetic
      benzimidazolone derivatives NS004 and NS1619 are the pioneer BK-activators and
      have represented the reference models which led to the design of several novel
      and heterogeneous synthetic BK-openers, while very few synthetic BK-blockers have
      been reported. Even today, the research towards identifying new BK-modulating
      agents is proceeding with great impetus and is giving an ever-increasing number
      of new molecules. Among these, also a handsome number of natural BK-modulator
      compounds, belonging to different structural classes, has appeared in the
      literature. The goal of this paper is to provide a possible simple classification
      of the broad structural heterogeneity of the natural BK-activating agents
      (terpenes, phenols, flavonoids) and blockers (alkaloids and peptides), and a
      concise overview of their chemical and pharmacological properties as well as
      potential therapeutic applications.

PMID- 14648390
TI  - Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity
      from Schinus molle fruits.
AB  - Three compounds with anti-inflammatory activity were isolated from Schinus molle
      fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid
      ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2,
      and biflavanone 3 were tested on two models of mice paw inflammation: one of
      acute inflammation, induced by subcutaneous injection of either phospholipase A
      (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation
      in the form of eczema, provoked by repeated administration of TPA to the ears of
      mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 %
      inhibition at 60 min), whereas all compounds reduced the chronic model of
      inflammation (48 to 26 % of swelling reduction), but only triterpenes reduced the
      leukocyte infiltration, measured as tissue peroxidase activity. In the case of
      the carrageenan-induced mouse paw oedema, only 3 led to a reduction of the
      swelling 3 h after challenge (50 mg/kg, 46 % oedema inhibition). In addition, 3
      inhibited the LTB (4) production in rat peritoneal polymorphonuclear leukocytes
      with an IC (50) value of 29.8 microM, while triterpenes showed toxicity against
      cells at 100 microM.

PMID- 14648391
TI  - Antirheumatoid arthritis effect of Rhus verniciflua and of the active component,
      sulfuretin.
AB  - Oral administration of the MeOH extract of Rhus verniciflua or of an EtOAc
      fraction containing an EtOAc-soluble portion of the MeOH extract slightly
      decreased rheumatoid arthritis (RA) and C-reactive protein (CRP) factors in
      Freund's complete adjuvant reagent FCA-treated rats, indicating that they are
      active extracts for rheumatoid arthritis, the EtOAc extract being more active.
      Treatment with these two extracts prevented histological changes such as synovial
      cell proliferation, inflammatory cell infiltration and fat necrosis compared with
      an FCA-treated group. Oral administration (30 mg/kg) of sulfuretin and fustin,
      which were isolated from the EtOAc extract by activity-guided separation,
      significantly decreased RA and CRP factors, the former being more active than the
      latter. Treatment with the EtOAc fraction ( p. o.) containing sulfuretin
      significantly decreased malondialdehyde (MDA) formation, and highly increased the
      activities of superoxide dismutase, catalase and glutathione peroxidase.
      Inhibition of xanthine oxidase and aldehyde oxidase in FCA-treated rats was also
      evident. Since treatment with sulfuretin and the EtOAc extract decreased the
      concentration of infiltrated mast cells in the rat knee exhibiting rheumatoid
      arthritis, we suggest that the Rhus verniciflua extract, which contains
      sulfuretin as an active component, may prevent rheumatoid syndromes by inhibiting
      reactive oxygen species.

PMID- 14648393
TI  - Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear
      cells.
AB  - In the last years several plant-derived natural compounds have been screened for
      their anti-HIV activity in order to find lead compounds with novel structures or
      mechanisms of action. Among these, several triterpenoids have been found to
      exhibit an antiretroviral activity with different mechanisms of action. In this
      study the effect of two limonoids, limonin and nomilin, on the growth of human
      immunodeficiency virus-1 (HIV-1) in culture of human peripheral blood mononuclear
      cells (PBMC) and on monocytes/macrophages (M/M) is described. Limonin and nomilin
      were found to inhibit the HIV-1 replication in all cellular systems used. A dose
      dependent inhibition of viral replication was observed in PBMC isolated from
      healthy donors and infected with HIV-1 strain after incubation with limonin and
      nomilin (EC (50) values: 60.0 microM and 52.2 microM, respectively). The two
      terpenoids inhibited at all concentrations studied the production of HIV-p24
      antigen even when the PBMC employed were chronically infected (EC (50) values of
      61.0 microM for limonin and 76.2 microM for nomilin). Moreover, these compounds
      inhibited the HIV-1 replication even in infected M/M. In this cellular system the
      inhibitory effect was significant at the concentrations of 20 microM, 40 microM
      and 80 microM starting from day 14 and reached the maximum effect after 18 days
      of incubation. As regards the mechanism of action, limonin and nomilin inhibit in
      vitro HIV-1 protease activity. In general, the results obtained point out a
      similar anti-HIV activity of limonin and nomilin indicating that this activity is
      not drastically influenced by the structural difference between the two
      compounds.

PMID- 14648392
TI  - Purification of gastroprotective triterpenoids from the stem bark of
      Amphipterygium adstringens; role of prostaglandins, sulfhydryls, nitric oxide and
      capsaicin-sensitive neurons.
AB  - In this investigation three bioactive compounds, responsible for the
      gastroprotective property of Amphipterygium adstringens, were purified from an
      active dichloromethane fraction. These compounds were 3alpha
      hydroxymasticadienonic acid, beta-sitosterol and 3- epi-oleanolic acid. The
      latter was the most active compound (88.8 % of gastroprotection) followed by
      3alpha-hydroxymasticadienoic acid and beta-sitosterol (69.8 and 42.5 % of
      gastroprotection, respectively). Carbenoxolone was used as positive control and
      it showed 88.4 % of gastroprotection. Masticadienonic acid was also isolated from
      the active fraction, but it was unable to inhibit the ethanol-induced gastric
      lesions. The gastroprotection of the methanol extract was completely inhibited by
      the pretreatment with l-NAME and attenuated by pretreatment with indomethacin and
      N-ethylmaleimide. These results suggest that endogenous nitric oxide plays an
      important role in the gastroprotection of A. adstringens methanol extract on
      ethanol-induced gastric mucosal lesions and that there is partial participation
      by prostaglandins and endogenous sulfhydryls. The effect of 3alpha
      hydroxymasticadienonic acid was attenuated only by pretreatment with N
      ethylmaleimide, indicating that endogenous sulfhydryls (thiols) participate in
      its gastroprotective mechanism. Capsaicin-sensitive afferent neurons do not
      participate in the gastroprotection of either the methanol extract or 3alpha
      hydroxymasticadienoic acid.

PMID- 14648394
TI  - Antitussive activity of Stemona alkaloids from Stemona tuberosa.
AB  - Bioactivity-directed fractionation of the crude extract of Stemona tuberosa led
      to the isolation and characterization of four new stenine-type Stemona alkaloids,
      namely tuberostemonine J ( 2), tuberostemonine H ( 3), epi
      bisdehydrotuberostemonine J ( 4) and neostenine ( 5), together with the known
      neotuberostemonine ( 1). These five isolated alkaloids were examined for
      antitussive activity in guinea pig after cough induction by citric acid aerosol
      stimulation. In this report, we demonstrated, for the first time, that compounds
      1 and 5 showed significant antitussive activities. Further study of the structure
      activity relationship on these isolated alkaloids and two synthetic analogues
      revealed that the saturated tricyclic pyrrolo[3,2,1- jk] benzazepine nucleus is
      the primary key structure contributing to the antitussive activity and all cis
      configurations at the three ring junctions are the optimal structure for the
      antitussive activity of stenine-type Stemona alkaloids.

PMID- 14648395
TI  - Cytotoxic activity of the seeds from Agrostemma githago var. githago.
AB  - In our investigations aqueous extracts of the seeds from Agrostemma githago L.
      proved to be remarkably more cytotoxic in comparison with isolated
      agrostemmasaponins in equal concentrations. A combination of agrostemmasaponin 1
      with a formyl function attached to triterpene position 4 together with agrostin,
      a ribosome-inactivating protein (RIP type 1; M (r): 27 kDa) which we isolated
      from the seed material, resulted in a markedly increased cytotoxicity. In analogy
      to the well-known lectin-like mechanism of action which can be inhibited by
      different monosaccharides, we tested seven different sugars known for their
      affinity to prevent cell recognition and thereby detoxify lectins. None of the
      tested monosaccharides diminished toxicity values significantly. This suggests
      that agrostin, combined with agrostemmasaponin 1, has a different mode of action
      to penetrate through the cell membrane than lectins. On the basis of these facts
      we concluded that both compounds work as a functional unity showing a mechanism
      of "cooperative toxicity".

PMID- 14648396
TI  - A mitogenic protein fraction in latex from Carica candamarcensis.
AB  - Latex from Caricaceae contains a number of proteins believed to be part of a
      defense mechanism that protects these plants from wounding. Prior evidence
      suggests that some components in Carica papaya improve healing of ulcerous wounds
      in mammals. This study shows the chromatographic isolation of a protein fraction
      from C. candamarcensis that stimulates cell proliferation of mammalian cells by
      measuring MTT reduction and thymidine incorporation. The effect appears to be
      cell specific as L929, MDA-MB231 and BHK-21 cells are stimulated while no effect
      is seen on CHO cells. The maximal stimulatory effect reaches 2.2-fold 72 h after
      addition of the active fraction to L929, 1.8-fold in MDA-MB231 cells and 1.6-fold
      in BHK cells. Proteolytic inactivation of the active fraction suggests that a
      protein is responsible for the proliferative activity and its size is estimated
      between 10 and 25 kDa. A potential candidate for this function is a 23 kDa
      protein found in the fraction that reacts with human EGF antibody.

PMID- 14648397
TI  - Antimicrobial compounds from Pimpinella species growing in Turkey.
AB  - A new, 4-(2-propenyl)-phenyl angelate ( 1) and four known phenylpropanoids ( 2 -
      5), were isolated from Pimpinella isaurica, a species endemic in Turkey. One new
      sesquiterpene, 1-methyl-4-(5-methyl-1-methylenehex-4-enyl)-7
      oxabicyclo[4.1.0]heptane ( 6) was obtained from P. aurea and two known
      phenylpropanoids were isolated ( 7, 8), from P. corymbosa. The structure
      elucidation of the new compounds 1 and 6 was achieved by a combination of one- (
      (1)H, and (13)C) and two-dimensional NMR techniques (G-DQF-COSY, G-HMQC, and G
      HMBC) and LC-ESI-FTMS. Compounds 1, 2, 4, 6, 7, 8 have been evaluated for their
      antimalarial and antimicrobial activities. Compound 1, 2, 4, 6, 8 had
      antimicrobial activity against Mycobacterium intracellulare with IC (50) values
      of 7.0, 15.0, 2.5, 10.0 and 1.5 microg/mL, respectively.

PMID- 14648398
TI  - Molecular genetic survey of European mistletoe (Viscum album) subspecies with
      allele-specific and dCAPS type markers specific for chloroplast and nuclear DNA
      sequences.
AB  - The qualitative and quantitative content of mistletoe metabolites, and
      bioactivity of extracts is related to the subspecies of Viscum album L. These
      were indicated to be genetically distinct and host specific. We aimed to check
      (i) whether the specificity is strict and (ii) how frequently hybridization
      occurs among the subspecies. We designed two sets of allele-specific and dCAPS
      molecular genetic markers that would facilitate identification of Viscum album L.
      subspecies and their hybrid derivatives on the basis of chloroplast trnH(GUG)-
      trnK(UUU) and nuclear rDNA ITS1&2 sequences. Out of 118 plants surveyed, 103
      displayed characteristics that confirmed strict host specificity of the
      subspecies, in addition, the results were compliant between nuclear and
      chloroplast markers showing no indication of hybridization among subspecies. From
      15 samples that showed deviations from this model 13 came from the Mediterranean
      Sea basin, and only two originated from Central and Western Europe.
      Abbreviations. dCAPS:derived Cleaved Amplified Polymorphic Sequence
      ITS1&2:Internal Transcribed Spacers 1&2 MAMA:Mismatch Amplification Mutation
      Assay

PMID- 14648399
TI  - Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and
      isolated flavones.
AB  - Recent cell culture experiments indicated that extracts of Vitex agnus-castus
      (VAC) may contain yet unidentified phytoestrogens. Estrogenic actions are
      mediated via estrogen receptors (ER). To investigate whether VAC compounds bind
      to the currently known isoforms ERalpha or ERss, ligand binding assays (LBA) were
      performed. Subtype specific ER-LBA revealed a binding of VAC to ERss only. To
      isolate the ERss-selective compounds, the extract was fractionated by bio
      guidance. The flavonoid apigenin was isolated and identified as the most active
      ERss-selective phytoestrogen in VAC. Other isolated compounds were vitexin and
      penduletin. These data demonstrate that the phytoestrogens in VAC are ERss
      selective.

PMID- 14648400
TI  - Saucernetin-7 and saucernetin-8 isolated from Saururus chinensis inhibit the LPS
      induced production of nitric oxide and prostaglandin E2 in macrophage RAW264.7
      cells.
AB  - In the present study, we demonstrate that saucernetin-8 ( 1) and saucernetin-7 (
      2), isolated from the underground parts of Saururus chinensis (Saururaceae),
      exerted potent inhibitory effects on LPS-induced nitric oxide (NO) and
      prostaglandin E (2) (PGE (2)) production in RAW 264.7 cells. Both compounds 1 and
      2, known as dineolignans, also suppressed the expression of iNOS and COX-2
      protein in a dose-dependent manner. Thus, this study suggests that compounds 1
      and 2-mediated inhibition of iNOS and COX-2 expression may be one of the
      mechanisms responsible for the anti-inflammatory effects of the underground parts
      of Saururus chinensis.

PMID- 14648401
TI  - Inhibitory effects of a new iridoid, patridoid II and its isomers, on nitric
      oxide and TNF-alpha production in cultured murine macrophages.
AB  - Patridoids I, II and IIA, are new iridoids isolated from the whole plants of
      Patrinia saniculaefolia. These compounds were examined by assessing their effects
      on the production of tumor necrosis factor-alpha (TNF-alpha) as well as by
      investigating the expression of two enzymes, inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2), in the lipopolysaccharide (LPS)-stimulated
      murine macrophage-like cell line, Raw 264.7. Among them, patridoid II
      consistently inhibited nitric oxide (NO) and TNF-alpha production in a dose
      dependent manner, with IC (50) values of 14.1 and 17.6 microM, respectively.
      Western Blotting probed with specific anti-iNOS antibodies showed that the
      decrease in the quantity of the NO product was accompanied by a decrease in the
      iNOS protein level. However, all three patridoids did not affect the COX-2
      protein expression level in the LPS-stimulated macrophages. In addition, the C-5
      isomer of patridoid II, patridoid I, only slightly affected the production of NO.
      Moreover, the C-3 isomer of patridoid II, patridoid IIA, did not inhibit
      proinflammatory cytokines and NO production. These results suggest that the
      orientations of the C-3 and C-5 methoxy groups in the patridoids have a
      significant role in the expression of their biological activity.

PMID- 14648402
TI  - In vitro antiviral activity of prodelphinidin B-2 3,3'-di-O-gallate from Myrica
      rubra.
AB  - In this study, the in vitro antiviral properties of prodelphinidin B-2 3,3'-di- O
      gallate (PB233'OG) isolated from the bark of Myrica rubra (Myricaceae) was
      investigated. Results showed that PB233'OG exhibited anti-herpes simplex virus
      type 2 (HSV-2) activity with IC (50) values of 5.3 +/- 0.1 and 0.4 +/- 0.04
      microM for XTT and plaque reduction assays, respectively. The IC (50) value
      increased with increasing MOI (multiplicity of infection). PB233'OG did not show
      a cellular cytotoxic effect at concentrations that possessed antiviral activity.
      Mechanistic studies demonstrated that PB233'OG inhibited HSV-2 attachment to the
      Vero cell, interfered with the penetration of HSV-2 into the Vero cell, affected
      the late stage(s) of the HSV-2 infection cycle, and also reduced the viral
      infectivity at high concentrations. It is concluded that PB233'OG exhibits
      various modes of action in its anti-HSV-2 effects.

PMID- 14648403
TI  - Pangelin, an antimycobacterial coumarin from Ducrosia anethifolia.
AB  - The aerial parts of Ducrosia anethifolia afforded the monoterpene glucoside 8
      debenzoylpaeoniflorin ( 1) and the prenylated furanocoumarin pangelin [5-[2"( R)
      hydroxy-3"-methyl-3"-butenyloxy]furocoumarin] ( 2). Their structures were
      determined by extensive 1- and 2-dimensional NMR studies. Compound 2 demonstrated
      activity against a panel of fast growing mycobacteria, namely Mycobacterium
      fortuitum, M. aurum, M. phlei and M. smegmatis and minimum inhibitory
      concentration (MIC) values ranged from 64 - 128 microg/mL. Whilst compounds 1 and
      2 have previously been reported as an antihyperglycaemic component from Paeonia
      lactiflora, and as a constituent of Angelica pancici, respectively, this is the
      first report of the full (1)H- and (13)C-NMR data for these natural products.

PMID- 14648404
TI  - Lignan profiles of indoor-cultivated Anthriscus sylvestris.
AB  - In a previous study we have shown that different populations of Anthriscus
      sylvestris (L.) Hoffm. (Apiaceae) yield significantly different lignan profiles.
      In this study we collected the seeds of A. sylvestris from 4 locations, one in
      England and three in The Netherlands. The seeds germinated and were grown under
      identical laboratory conditions. After 5 months the plants were harvested and the
      lignan profile in the roots and aerial parts was analysed using GC-MS. The plants
      from the seeds of the 4 locations showed several significant phenotypic
      differences in, for instance, dry-weight. However the 4 groups did not differ
      significantly in their lignan profile in their roots. The lignans in the roots of
      A. sylvestris, deoxypodophyllotoxin, yatein and anhydropodorhizol reached, on
      average, equal amounts in all 4 groups. Within the 4 groups, however, a large
      quantitative variation in lignan profile between the individual plants was
      observed, pointing to within-population genetic differences between individual
      plants.

PMID- 14648405
TI  - Two new guaianolides and a new daucene derivative from Sinodielsia yunnanensis.
AB  - From the roots and rhizomes of Sinodielsia yunnanensis, three new sesquiterpenes
      were isolated and their structures were established as 5alpha,6beta- H
      1(10),3,7(11)-guaiatrien-12,6alpha-olide ( 1), 5alpha,6beta,7beta- H-1(10),3
      guaiadien-12,6alpha-olide ( 2) and 5beta-hydroxy-10alpha- O-angeloyl-3-oxodauc-8
      ene ( 3) by means of spectroscopic analyses and single-crystal X-ray experiment
      (for compound 1).

PMID- 14648406
TI  - Cyclized geranyl stilbenes from the rhizomes of Helminthostachys zeylanica.
AB  - Three new cyclized geranyl stilbenes, ugonstilbene A ( 1), ugonstilbene B ( 2),
      and ugonstilbene C ( 3), and one known compound 3-hydroxyacetophenone, were
      isolated from the dried rhizomes of H. zeylanica. The structures of these three
      new compounds were elucidated on the basis of spectral analysis. Compounds 1 - 3
      exhibited moderate antioxidant activity by the DPPH assay with IC (20) of 11.31
      +/- 1.11, 38.72 +/- 0.47, and 30.80 +/- 1.19 microM, respectively, while the IC
      (20) of Trolox was 8.70 +/- 0.95 microM.

PMID- 14648407
TI  - Two new benzofuranes from Eupatorium aschenbornianum and their antimicrobial
      activity.
AB  - Through a bioassay-guided fractionation, from the aerial parts of the medicinal
      plant Eupatorium aschenbornianum were isolated two new benzofurane compounds, 5
      acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-2,3-dihydrobenzofurane ( 1)
      and 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-6-methoxy-2,3
      dihydrobenzofurane ( 2) in addition to 4-hydroxy-3,5-diprenylacetophenone,
      espeletone ( 3), encecalinol ( 4), beta-sitosterol and stigmasterol. The
      antimicrobial evaluation of these natural products showed that 1 [MIC = 200
      microg/mL against T. mentagrophytes and 100 microg/mL against T. rubrum], 2 [MIC
      = 50 microg/mL towards both] and 3 [MIC = 100 microg/mL against both] were active
      against dermatophytes, while 4 was active against all of microorganisms assayed
      [MIC = 12.5 microg/mL ( T. mentagrophytes), 12.5 microg/mL ( T. rubrum), 100
      microg/mL ( C. albicans) and 200 microg/mL ( A. niger)].

PMID- 14648408
TI  - Double-balloon enteroscopy: preliminary experience in patients with obscure
      gastrointestinal bleeding or chronic abdominal pain.
AB  - BACKGROUND AND STUDY AIMS: Even in the era of capsule endoscopy, diseases of the
      small bowel are sometimes difficult to diagnose, and endoscopic treatment is not
      possible without surgical laparotomy. The new method of carrying out enteroscopy
      using a double-balloon technique allows not only diagnostic but also therapeutic
      endoscopic interventions for lesions in the small bowel. Preliminary experience
      with this new method is reported here. PATIENTS AND METHODS: Between the end of
      March 2003 and August 2003, eight patients (four women, four men; mean age 59 +/-
      23 years, range 20 - 90) with chronic gastrointestinal bleeding or abdominal
      pain, or both, underwent enteroscopy using the double-balloon technique. Seven of
      the patients had been suffering from chronic gastrointestinal bleeding for 56 +/-
      49 months (range 3 - 120 months, median 48 months). The lowest hemoglobin levels
      ranged from 3.6 g/dl to 8.6 g/dl (mean 6.7 +/- 1.7 g/dl), and a mean of 7.6 +/-
      5.6 (range 1 - 15) blood units had been transfused. Capsule endoscopy was carried
      out in six patients, revealing angiodysplasias in three, suspected Crohn's
      disease in one, fresh blood in the small bowel without a lesion in one, and a
      focal enanthema in another patient. RESULTS: Enteroscopy with the double-balloon
      technique was carried out using the oral approach in all patients and
      additionally with the anal approach in four patients. In two patients with
      multiple angiodysplasias, it was possible to examine the whole small bowel and to
      treat the angiodysplasias. All of the capsule endoscopy findings were confirmed;
      a definite bleeding source was found and treated in two patients with unclear
      bleeding, and in another patient the real bleeding source was found (not
      angiodysplasia). The enteroscopy system was easy to handle in all cases. No
      complications occurred. It was possible to carry out the procedure with the
      patients under sedoanalgesia. CONCLUSIONS: This new enteroscopy system is easy to
      handle and seems to be safe. Visualization of the whole small bowel is possible
      using both the oral and anal approaches. Enteroscopy with the double-balloon
      technique promises to become a standard method for diagnostic and therapeutic
      endoscopy of the small bowel without surgical laparotomy.

PMID- 14648409
TI  - A prospective, randomized multicenter trial comparing DoubleLayer and
      polyethylene stents for malignant distal common bile duct strictures.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic biliary stenting is an established
      treatment for malignant obstructive jaundice. Stent clogging continues to be a
      major problem with plastic stents. The aim of this study was to carry out a
      prospective comparison of two stents with different materials and shapes: the
      Olympus DoubleLayer stent (DLS; perfluoro alkoxy, without sideholes) and the
      standard polyethylene (PE) stent (with sideholes). PATIENTS AND METHODS: A total
      of 120 patients (70 women; mean age 71, range 36 - 91) with jaundice due to
      malignant strictures of the middle to distal third of the common bile duct were
      randomly assigned to receive either DLS (n = 60) or PE (n = 60) biliary stents.
      Patients with cholangitis, hemobilia, previous biliary drainage, hilar stricture,
      or ampullary cancer were excluded. RESULTS: In all, 28 DLS patients (47 %) and 17
      PE stent patients (29 %) died without clinical evidence of stent occlusion after
      a mean of 114 and 105 days, respectively ( P < 0.05). Twenty-six DLS patients (43
      %) and 38 PE stent patients (63 %) had symptoms of stent clogging after a mean of
      144 and 99 days, respectively ( P < 0.05). Stent dysfunction (stent orifice
      impacted on the bile duct or duodenal wall, stent migration) was recorded in six
      DLS patients (10 %) and five PE patients (8 %) (n. s.). Kaplan-Meier analysis of
      DLS and PE stent clogging-free survival showed a significantly longer patency
      period with the DLS stents (P = 0.0005). CONCLUSIONS: These results show that
      DoubleLayer stents have a longer patency period than PE stents. Patients who
      received PE stents had a higher risk of stent occlusion (relative risk 3.05; 95 %
      CI, 1.57 - 5.89) before death than DLS patients.

PMID- 14648410
TI  - A randomized, prospective cross-over trial comparing methylene blue-directed
      biopsy and conventional random biopsy for detecting intestinal metaplasia and
      dysplasia in Barrett's esophagus.
AB  - BACKGROUND AND STUDY AIMS: The value of methylene blue-directed biopsies (MBDB)
      in detecting specialized intestinal metaplasia and dysplasia in Barrett's
      esophagus remains unclear. The aim of this study was to compare the accuracy of
      MBDB with random biopsy in detecting intestinal metaplasia and dysplasia in
      patients with Barrett's esophagus. PATIENTS AND METHODS: A prospective,
      randomized, cross-over trial was undertaken to compare MBDB with random biopsy in
      patients with Barrett's esophagus segments 3 cm or more in length without
      macroscopic evidence of dysplasia or cancer. Dysplasia was graded as: indefinite
      for dysplasia, low-grade dysplasia, high-grade dysplasia, or carcinoma, and was
      reported in a blinded fashion. RESULTS: Fifty-seven patients were recruited, 44
      of whom were male. A total of 1,269 biopsies were taken (MBDB-651, random biopsie
      618). Analysis of the results by per-biopsy protocol showed that the MBDB
      technique diagnosed significantly more specialized intestinal metaplasia (75 %)
      compared to the random biopsy technique (68 %; P = 0.032). The sensitivity and
      specificity rates of MBDB for diagnosing specialized intestinal metaplasia were
      91 % (95 % CI, 88 - 93 %) and 43 % (95 % CI, 36 - 51 %), respectively. The
      sensitivity and specificity rates of MBDB for diagnosing dysplasia or carcinoma
      were 49 % (95 % CI, 38 - 61 %) and 85 % (95 % CI, 82 - 88 %), respectively. There
      were no significant differences in the diagnosis of dysplasia and carcinoma -
      MBDB 12 %, random biopsy 10 %. The methylene blue staining pattern appeared to
      have an influence on the detection of specialized intestinal metaplasia and
      dysplasia/carcinoma. Dark blue staining was associated with increased detection
      of specialized intestinal metaplasia (P < 0.0001), and heterogeneous staining (P
      = 0.137) or no staining (P = 0.005) were associated with dysplasia and/or
      carcinoma detection. The MBDB technique prolonged the endoscopy examination by an
      average of 6 min. CONCLUSION: The diagnostic accuracy of the MBDB technique was
      superior to that of the random biopsy technique for identifying specialized
      intestinal metaplasia, but not dysplasia or carcinoma. The intensity of methylene
      blue staining has an influence on the detection of specialized intestinal
      metaplasia and dysplasia or carcinoma, which may help in targeting the biopsies.
      Although MBDB prolongs the endoscopy procedure slightly, it is a safe and well
      tolerated procedure. Further clinical studies on the MBDB technique exclusively
      in endoscopically normal dysplastic Barrett's esophagus are needed.

PMID- 14648411
TI  - Diagnosing colitis: a prospective study on essential parameters for reaching a
      diagnosis.
AB  - BACKGROUND AND STUDY AIMS: It is generally believed that making a correct
      histological diagnosis of colitis at colonoscopy requires segmental mucosal
      biopsies, information on the endoscopic features, and clinical data. This
      prospective study was carried out to determine the essential parameters required
      for an accurate diagnosis of colitis. PATIENTS AND METHODS: Two hundred
      consecutive patients with suspected or established colitis who underwent
      colonoscopy were prospectively examined. A double biopsy was taken at a
      macroscopic site of typical inflammation, or, if no abnormalities could be found,
      from normal mucosa. In addition, segmental biopsies were obtained. Endoscopic
      features and the patient's clinical history and symptoms were recorded. Histology
      was analyzed by providing the pathologist with the double-biopsy sample,
      segmental biopsies, and endoscopic and clinical information in a segmental
      fashion. Changes in the diagnoses were noted after each step of the analysis.
      RESULTS: Colitis was diagnosed in 152 patients (76 %). Double-biopsy examination
      provided the correct final diagnosis in 66 % of cases. After assessment of the
      segmental biopsies, the diagnosis had to be changed in 26 % of cases. Information
      on the endoscopic features altered the diagnosis in 2.5 %. Finally, the diagnosis
      was changed in an additional 5.5 % of cases after clinical data (the patient's
      history and symptoms) had been provided. CONCLUSIONS: Segmental biopsy specimens
      are essential for the differential diagnosis of intestinal inflammation.
      Information on the endoscopic features and clinical data are useful in
      differentiating some forms of colitis.

PMID- 14648412
TI  - Diagnostic yield of wireless capsule enteroscopy in comparison with computed
      tomography enteroclysis.
AB  - BACKGROUND AND STUDY AIMS: It is still difficult to visualize changes in the
      small intestine. Wireless capsule enteroscopy is a new method that promises to
      provide new insights into the small intestine. In a prospective study, the
      diagnostic yield of wireless enteroscopy was therefore compared with computed
      tomography (CT) enteroclysis. PATIENTS AND METHODS: Twenty-two patients with
      suspected small-bowel pathology underwent CT enteroclysis and wireless capsule
      enteroscopy examinations, conducted by two independent blinded investigators. The
      results of the two investigations (diagnoses and the number, extent, and location
      of lesions detected) were compared by a third investigator. RESULTS: The patients
      included in the study had obscure gastrointestinal bleeding (n = 8), Crohn's
      disease (n = 8), unexplained diarrhea (n = 5), or suspected carcinoid tumor (n =
      1). Pathological lesions were detected using capsule enteroscopy in 13 patients
      (59 %) and using CT enteroclysis in eight (36 %; P = 0.12). In seven patients
      (one case each of colonic Crohn's disease, diverticulitis, Meckel's diverticulum,
      carcinoid tumor, mesothelioma, colonic polyps, and irritable bowel syndrome), no
      pathological changes were found in the small intestine using either method. The
      diagnosis was established by wireless capsule enteroscopy in four patients with
      obscure bleeding, whereas CT enteroclysis was positive in only one patient ( P =
      0.1). Crohn's disease was found in two patients with unexplained diarrhea. Small
      bowel lesions were identified in six patients with known Crohn's disease using
      capsule enteroscopy or CT enteroclysis. The only side effect of wireless capsule
      enteroscopy observed was abdominal pain in one patient with Crohn's disease.
      There were no serious side effects with CT enteroclysis. CONCLUSIONS: Wireless
      capsule enteroscopy detects more small-bowel lesions than CT enteroclysis in
      patients with obscure gastrointestinal bleeding and Crohn's disease.

PMID- 14648413
TI  - Prevalence and significance of periduodenal venous collaterals in patients
      evaluated for pancreaticobiliary disorders by endosonography.
AB  - BACKGROUND AND STUDY AIMS: The prevalence of periduodenal venous collaterals
      detected by endoscopic ultrasonography (EUS) in patients undergoing evaluation
      for pancreaticobiliary disorders, and their influence on the success of
      transduodenal fine-needle aspiration (FNA) of solid pancreatic masses is not
      known. PATIENTS AND METHODS: Records for all consecutive patients who underwent
      EUS for pancreaticobiliary disorders over a 14-month period were reviewed. EUS
      was carried out by a single endosonographer using a radial echo endoscope. When
      FNA was attempted, a curvilinear-array echo endoscope was used in conjunction
      with color flow Doppler. Periduodenal and perigastric collaterals were defined as
      multiple anechoic serpiginous structures imaged from the duodenal bulb, the
      second portion of duodenum, or the stomach. Established criteria were used to
      assess the presence of chronic pancreatitis. RESULTS: Over the study period, 338
      patients (mean age 58.9 +/- 14.5 years; 52 % women) underwent EUS for
      pancreaticobiliary disorders. Periduodenal collaterals were detected in 22
      patients (6.5 %), 21 of whom (19 %) had pancreatic cancer. Patients with
      pancreatic cancer were significantly more likely to have periduodenal collaterals
      in comparison with those without pancreatic cancer (OR 25; 95 %CI, 5.75 - 109; P
      = 0.001). Computed tomography detected collaterals in only two of the 22 patients
      (9.1 %). Periduodenal collaterals made transduodenal FNA impossible in nine of
      the 22 patients (41 %). However, in these patients a cancer diagnosis was
      obtained using EUS-FNA from liver lesions in two cases; using a transgastric
      approach in two (pancreatic neck lesions); and atypical cells were obtained in
      two. A safe window could not be achieved in three patients (13.6 %).
      Transduodenal FNA was performed by avoiding the collaterals and was successful in
      13 of the 22 patients, with no bleeding complications. CONCLUSIONS: Periduodenal
      collateral vessels are infrequent in patients with suspected pancreaticobiliary
      disease, but are relatively common in patients with pancreatic cancer.
      Transduodenal EUS-FNA can be carried out safely in the majority of cases in the
      presence of periduodenal collaterals, but collaterals may occasionally hamper
      successful transduodenal pancreatic FNA.

PMID- 14648414
TI  - Training in radial EUS: what is the best approach and is there a role for the
      nurse endoscopist?
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to determine the relative
      contribution of previous endoscopic experience, case observation, and hands-on
      experience to skill acquisition in radial EUS. METHODS: In EUS trainees, four
      senior gastroenterology fellows, and a nurse endoscopist, the ability to
      reproduce set views from the mediastinum, stomach, and duodenum was assessed.
      Points were ascribed to static and dynamic stations and to the use of console
      controls. RESULTS: Trainees observed 55 - 170 cases and conducted 25 - 124
      examinations. Competence was demonstrated after performing approximately 25
      examinations in the mediastinum, 35 examinations in the stomach, and 78
      examinations in the duodenum. The number of previous examinations conducted
      correlated with the ability to scan the duodenum ( P < 0.01). Observation of 100
      or more further procedures early in training did not accelerate learning. The
      nurse endoscopist showed a comparable degree of competence in mediastinal
      scanning to that of the other trainees after performing a similar number of
      examinations. CONCLUSIONS: Proficiency in radial endosonography is greatly
      influenced by the numbers of examinations performed. Observing large numbers of
      cases early in training does not appear to translate into competence. A
      background in advanced therapeutic endoscopy is not a prerequisite for acquiring
      endoscopic ultrasound skills. Nurse endoscopists may be expected to train
      successfully in mediastinal imaging at the same pace as senior gastroenterology
      fellows.

PMID- 14648415
TI  - Tolerance and efficacy of argon plasma coagulation for controlling bleeding in
      patients with typical and atypical manifestations of watermelon stomach.
AB  - BACKGROUND AND STUDY AIMS: Watermelon stomach is a well-known cause of
      gastrointestinal bleeding and anemia. This study investigated the efficacy of and
      patient tolerance for argon plasma coagulation (APC) in this condition. PATIENTS
      AND METHODS: The reports of 21 patients with watermelon stomach who were treated
      using APC from February 1998 to August 2001 were reviewed. The efficacy of APC
      was evaluated on the basis of the patients' symptoms, transfusion requirements,
      and hemoglobin levels. RESULTS: Fifty-nine APC sessions were carried out (mean
      2.81 sessions per patient, range one to five). Depending on the bleeding outcome
      and lesion intensity, repeat treatments were carried out with a mean delay of 1.8
      months (range 2 days - 6 months). The mean follow-up period after the last
      session was 14.9 months (1 - 60.6 months). All of the patients required repeated
      blood transfusions before APC, compared with only two patients after treatment.
      One of these two patients died of uncontrolled bleeding despite APC. The mean
      hemoglobin level was 80.9 g/l before treatment, compared with 103.2 g/l after
      treatment. Three patients had recurrent bleeding 4.4 - 31.7 months (mean 13.8
      months) after the last session and required a further session of APC, which
      controlled bleeding in all cases. Complications encountered consisted of two
      cases of hematemesis and one of sepsis. CONCLUSIONS: APC was effective in
      controlling bleeding due to watermelon stomach in the great majority of patients,
      with a low complication rate.

PMID- 14648416
TI  - Is there a difference in diagnostic accuracy and clinical impact between
      endoscopic ultrasonography and magnetic resonance cholangiopancreatography?
AB  - BACKGROUND AND STUDY AIMS: It is still unknown whether there is a difference in
      diagnostic accuracy and clinical impact between endoscopic ultrasonography (EUS)
      and magnetic resonance cholangiopancreatography (MRCP). PATIENTS AND METHODS: The
      test performance and potential clinical impact of EUS and MRCP, had each
      investigation been performed as the first examination method, were compared
      prospectively in 163 patients admitted for and examined by endoscopic retrograde
      cholangiopancreatography (ERCP). RESULTS: The accuracies of EUS and MRCP were
      0.93 and 0.91, respectively (no significant difference, P > 0.05). Had EUS or
      MRCP been performed as the first investigation in the 75 patients who had a
      presumed high probability for needing therapeutic ERCP, only 15 and nine
      patients, respectively, would have avoided ERCP. In this group of patients, one
      patient needed other diagnostic investigations following EUS compared with 11
      patients following MRCP ( P = 0.004). For the 57 patients with an intermediate
      probability of needing endoscopic therapy, EUS and MRCP would have spared 37 and
      38 patients, respectively, from the need to have an ERCP. In 31 patients with a
      presumed low risk of needing endoscopic therapy, 30 and 29 patients would have
      been spared from ERCP had EUS and MRCP, respectively, been performed initially.
      CONCLUSIONS: There was no difference in the diagnostic accuracy and clinical
      impact between EUS and MRCP in the majority of the patients. The impact of EUS or
      MRCP on the ERCP workload was highly dependent on the presumed probability of
      needing endoscopic therapy.

PMID- 14648418
TI  - Silent myocardial ischaemia during endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND AND STUDY AIMS: Myocardial ischaemia may occur during endoscopic
      retrograde cholangiopancreatography (ERCP) and this may predispose patients to
      ischaemic complications, although the incidence and risk factors for mycocardial
      ischaemia during ERCP have not been studied in detail. The aim of this study was
      to determine the incidence of myocardial ischaemia, as defined by ST changes on
      electrocardiography during ERCP, and whether or not any intervention predisposes
      to an increased risk of myocardial ischaemia. PATIENTS AND METHODS: Consecutive
      patients undergoing ERCP at a single centre were included. Continuous Holter
      electrocardiograph recordings were carried out during ERCP. ST depression was
      defined as > 1 mm lasting for longer than 1 minute. The time of interventions
      during ERCP was recorded prospectively and related to the Holter recordings.
      RESULTS: There were 41 patients in the study (14 men, 27 women; median age 66
      years, range 21 - 88). Nine patients (22 %) experienced ST depression during the
      procedure, of whom four (10 %) showed significant ST depression (> or = - 2 mm).
      Of these, five had no previous cardiac history and normal electrocardiographic
      findings, three had no previous cardiac history but had abnormal
      electrocardiographic findings and one had a previous cardiac history and abnormal
      electrocardiographic results. ERCP interventions associated with the episodes of
      ST depression were administration of sedation ( n = 6, P < 0.01) endoscopic
      sphincterotomy ( n = 4), balloon trawl ( n = 1), basket trawl ( n = 3) and stent
      replacement ( n = 1) ( P > 0.05 for the rest). No cardiac complications occurred.
      CONCLUSIONS: Myocardial ischaemia occurred in approximately one-quarter of
      patients during ERCP, and over half of these had no previous cardiac history and
      normal baseline electrocardiography results. Myocardial ischaemia often
      accompanied the use of sedation and intubation of the patient, but specific
      therapeutic interventions were not associated with the onset of ischaemia.

PMID- 14648417
TI  - Virtual histology of colorectal lesions using laser-scanning confocal microscopy.
AB  - BACKGROUND AND STUDY AIMS: Histological examination of gastrointestinal lesions
      is currently based on light-microscopic examination of thin-slice specimens, with
      hematoxylin and eosin staining. A study of the use of laser-scanning confocal
      microscopy (LCM) to obtain immediate microscopic images of untreated specimens
      for examining colorectal lesions was carried out. A probe-type LCM prototype
      endomicroscope that can be passed through the working channel of an endoscope has
      also been developed. MATERIALS AND METHODS: The study materials consisted of
      colorectal lesions resected either endoscopically or surgically at Showa
      University Northern Yokohama Hospital. One hundred untreated specimens were
      examined using LCM. The histopathological findings in the lesions were seven
      cases of normal colonic mucosa, five hyperplastic polyps, 68 adenomas with low
      grade dysplasia, 10 adenomas with high-grade dysplasia, and 10 adenocarcinomas.
      An argon laser beam with a wavelength of 488 nm was used for the LCM study.
      Observation of the resected normal colonic mucosa (in vitro) and the rectal
      mucosa of a healthy volunteer (in vivo) was possible using the endomicroscope.
      The LCM images for each specimen were compared with the hematoxylin-eosin-stained
      histopathological cross-sections. RESULTS: The LCM images corresponded well with
      the conventional hematoxylin-eosin light-microscopic images. The nuclei were not
      visualized in normal mucosa or hyperplastic polyps. In adenomas with high-grade
      dysplasia and carcinomas, nuclei were more often visible than in adenomas with
      low-grade dysplasia. The rate of visualization of nuclei was significantly
      different ( P < 0.01) between these two groups (60.0 % vs. 10.3 %). In LCM images
      using endomicroscope, it was possible to recognize the orifices of the colonic
      glands and goblet cells both in vitro and in vivo. CONCLUSIONS: Laser-scanning
      confocal microscopy provides immediate images that correspond well with those of
      hematoxylin-eosin staining. An improved probe-type LCM endomicroscope is being
      developed which should provide better histological images of colorectal lesions
      in vivo.

PMID- 14648419
TI  - Photodynamic therapy of esophageal varices: experimental studies in animal veins,
      and first clinical cases.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic injection sclerotherapy and endoscopic
      variceal ligation have been found to have shortcomings in the treatment of
      esophageal varices. In this study the effectiveness of photodynamic therapy (PDT)
      in the obliteration of veins was investigated to evaluate its potential in the
      treatment of esophageal varices. METHODS: Auricular margin veins of rabbits were
      irradiated by copper vapor laser after intravenous injection of 10 mg/kg of
      hematoporphyrin monomethyl ether (which is a hematoporphyrin derivative) into the
      rabbits. Control groups included rabbits that received irradiation only, that
      received injection of photosensitizer only, and that received injection
      sclerotherapy (using sodium morrhuate). The treated areas were observed
      macroscopically and also identified using with ultrasonic miniprobe. Biopsies
      were performed and the specimens were examined microscopically after hematoxylin
      eosin staining and Victoria blue staining. In addition, two patients with newly
      visible veins within the esophageal wall after endoscopic injection sclerotherapy
      underwent PDT. Intravenous injection of 5 mg/kg of hematoporphyrin monomethyl
      ether was given, and the newly visible veins were endoscopically irradiated by
      copper vapor laser. Endoscopic re-examination was performed 1 month later to
      evaluate the therapeutic effect. RESULTS: Thrombi of the auricular margin vein
      were formed and blood flow was obstructed after PDT. Thrombus formation and
      diffused necrosis of adjacent tissue was found after injection of sodium
      morrhuate. On ultrasonic examination, the lumina of the veins showed a slightly
      higher echo after PDT compared with a lower echo before treatment, which was
      another sign of thrombus formation. The rabbit ears showed a diffused low echo
      after injection of sodium morrhuate, indicating diffuse necrosis. On microscopic
      observation, destruction of the endothelium and formation of thrombus was seen
      after PDT. Further observation of specimens stained with Victoria blue showed
      that the layer of elastic fiber was intact. After injection of sodium morrhuate,
      extensive necrosis of tissue was seen microscopically. No macroscopic,
      ultrasonic, or microscopic change was found in the rabbits that received
      irradiation only or injection of photosensitizer only. The rate of thrombus
      formation in rabbits that received PDT was significantly higher than that in the
      rabbits that received irradiation only or injection of photosensitizor only ( P =
      0.015, P = 0.015), and comparable to that in the rabbits that received
      sclerotherapy ( P = 0.467). In the clinical study, at endoscopy 1 month after PDT
      both the number and the "red sign" of newly visible veins were found to have
      decreased. No adverse effect was found. CONCLUSION: PDT can destroy the
      endothelium of the vein, result in thrombus formation, and eventually obliterate
      the vein. It is potentially a new method for the treatment of esophageal varices.

PMID- 14648420
TI  - Interventional radiology for the management of inoperable carcinoma of the
      oesophagus.

PMID- 14648421
TI  - Photodynamic therapy for esophageal diseases: a clinical update.
AB  - Photodynamic therapy (PDT) is a "drug and device" therapy that combines the use
      of a photosensitizing agent and a photosensitizer (a drug that selectively
      accumulates and is preferentially retained in dysplastic or neoplastic cells).
      When activated by light of a specific wavelength in the presence of oxygen, the
      photoactive compound produces rapid cell death in the target tissue. While
      studied in nearly every area of medicine, PDT has been applied most extensively
      in the treatment of Barrett's mucosa, dysplasia, and early and advanced cancer of
      the esophagus. This article represents an extensive survey of literature to
      review the experience gained with PDT and to assess its clinical value in the
      management of esophageal diseases.

PMID- 14648422
TI  - A gastric hyperplastic polyp observed endoscopically before and after
      autoamputation.
AB  - Autoamputation of a gastric polyp is a relatively rare phenomenon and its precise
      mechanism is unclear. To learn more about the mechanism(s) involved, it is
      important to observe a polyp just before and just after its disappearance. We
      report a case of a gastric polyp that was observed endoscopically just before and
      then just after autoamputation. A 61-year-old woman with a thumb-sized,
      pedunculated hyperplastic polyp in the gastric antrum visited our institution for
      investigation of hematemesis. She was being treated with oral hypoglycaemic drugs
      for diabetes mellitus but was not taking any other medicine around that time.
      Emergency gastroscopy revealed a bleeding point near the polyp; gastroscopy the
      next day revealed that the polyp had disappeared. It was concluded that
      autoamputation of a gastric polyp may follow gastric injury induced by diabetes
      mellitus or oral antidiabetic drugs.

PMID- 14648423
TI  - Spontaneous flow of bile through the human pancreatic duct in the absence of
      pancreatitis: nature's human experiment.
AB  - One hundred years ago E. L. Opie proposed two distinct hypotheses to address the
      pathogenesis of gallstone-induced pancreatitis. These hypotheses appear mutually
      exclusive. The first predicts that impediment to the flow of pancreatic juice
      causes pancreatitis (the pancreatic duct obstruction hypothesis), whereas the
      second predicts that bile flow into the pancreatic duct behind an impacted
      gallstone would trigger the onset of acute pancreatitis (the common-channel
      hypothesis). One of the more convincing arguments against the latter hypothesis
      is the observation that bile, when experimentally perfused through the pancreatic
      duct of dogs, does not induce pancreatitis. This experimental situation had
      spontaneously developed in the patient we describe here: a biliopancreatic
      fistula had permitted the continuous flow of bile through a large portion of the
      pancreas, which was associated with cholangitis but had apparently never led to
      pancreatitis. This patient's case would suggest that in humans, just as in
      experimental animals, bile flow through the pancreatic duct is not necessarily
      involved in the onset of gallstone-induced pancreatitis and lends further support
      to Opie's pancreatic duct obstruction hypothesis.

PMID- 14648424
TI  - Hepaticogastrostomy by echo-endoscopy as a palliative treatment in a patient with
      metastatic biliary obstruction.
AB  - A palliative hepaticogastrostomy was performed under endoscopic ultrasound
      guidance in a patient with inoperable hepatic hilar obstruction, creating an
      anastomosis between the dilated left hepatic duct and the stomach, to relieve
      symptoms of cholangitis and to allow biliary drainage. This therapeutic procedure
      was used as an alternative method of drainage of the biliary tree because
      endoscopic retrograde cholangiopancreatography was not possible and because the
      percutaneous metallic stent which had been inserted earlier had become occluded
      (probably by tumor overgrowth). It was a two-step procedure. In the first step a
      hepatic duct was punctured through the gastric wall with placement of a plastic
      stent, which created a fistula between them. In a second step a covered,
      metallic, self-expandable stent was substituted for the plastic stent to maintain
      the anastomosis and to improve patency over the medium term. The patient's fever
      was relieved and the bilirubin level fell; the patient remained asymptomatic at
      the five-months-follow-up.

PMID- 14648425
TI  - Laparoscopy and guided liver biopsy in the diagnosis of cirrhosis: conventional
      technique vs. minilaparoscopy.

PMID- 14648427
TI  - Treatment of colovaginal fistula with coaxial placement of covered and uncovered
      stents.

PMID- 14648428
TI  - Severe ulceration of the stomach after endoscopic injection sclerotherapy.

PMID- 14648429
TI  - Solid pseudopapillary tumor of the pancreas: diagnosis by EUS-guided fine-needle
      aspiration.

PMID- 14648430
TI  - Complications of colonic stenting: a case of stent migration and fracture.

PMID- 14648431
TI  - Use of a duodenoscope in the management of a ureteral calculus in a patient with
      ureterosigmoidostomy (Mainz pouch II; rectosigmoid pouch).

PMID- 14648432
TI  - Diagnosis of Fasciola hepatica by endoscopic ultrasound.

PMID- 14648434
TI  - [Polymethylmethacrylate-vertebroplasty. A new and effective method of pain
      treatment in vertebral compression].
AB  - BACKGROUND AND OBJECTIVE: Percutaneous polymethylmethacrylate (PMMA)
      vertebroplasty is increasingly used in the treatment of back pain related to
      compression of the vertebral bodies. After the procedure immediate mobilization
      of the patient is possible. The purpose of the study was to examine the change in
      quality of life of patients with vertebral collapse achieved by vertebroplasty
      during a six-month period. PATIENTS AND METHODS: 28 patients with osteolytic
      metastases (mean age 59,7 +/- 7,8 years, 2,1:1male/female ratio) and 38 patients
      with osteoporotic vertebral collapse (mean age 73 +/- 6 years, 1:3,5male/female
      ratio ) of the thoracal and lumbar spine were treated with PMMA vertebroplasty
      and analysed prospectively. After admission, before, six weeks and 6 months after
      discharge from the hospital patients answered the Oswestry Low Back Pain
      Disability (OLBPD) questionnaire for assessment of treatment-related changes in
      disability. RESULTS: Immediately and 6 months after treatment 83 % of tumor
      patients and 92 % of ostoporotic patients had significant pain reduction.
      Extravasation of PMMA beyond the vertebral margins were observed in 26 % of the
      patients. No treatment-related clinical or neurological complications were
      observed. CONCLUSION: PMMA vertebroplasty is an efficacious and safe method of
      pain relief for patients with osteolytic metastases or osteoporotic compression
      with good long-term results.

PMID- 14648435
TI  - [Fungemia after oral treatment with Saccharomyces boulardii in a patient with
      multiple comorbidities].
AB  - HISTORY AND CLINICAL FINDINGS: A 48-year-old diabetic with multiple co
      morbidities presented with generalized micro- and macroangiopathy including
      peripheral artery disease stage IV with necroses in several digits of both feet.
      He was admitted to the department of surgery for the insertion of femoropopliteal
      bypasses. INVESTIGATIONS: Infectious parameters were elevated (CRP 66.1 mg/l,
      sedimentation rate 90/96), accompanied by anemia (Hb 7.1 mmol/l), leukocytosis
      (14.8 Gpt/l) and thrombocytosis (514 Gpt/l). Body temperature was normal (36.8
      degrees C). With insulin treatment the patient became nearly normoglycemic (HbA1c
      6.8 %). TREATMENT AND FOLLOW UP: After receiving different broad-spectrum
      antibiotics over seven weeks the patient developed Clostridium difficile toxin
      positive diarrhea that resolved after administration of oral metronidazole and
      Saccharomyces boulardii (Perenterol ((R))). Three days after bypass insertion,
      both legs had to be amputated due to infection and beginning sepsis. The
      condition of the patient improved. However, eight days after bypass-insertion the
      patient developed a toxic megacolon and sepsis. Blood cultures yielded the growth
      of Saccharomyces cerevisae. Despite of intensive care treatment the patient died
      five days later from to multi-organ failure. CONCLUSION: S. boulardii (synonym:
      S. cerevisiae) is considered an non-pathogenic probiotic yeast, and live yeast
      cells are used for supportive therapy of diarrhea. The present case and a review
      of the literature demonstrate that fungemia and sepsis are rare complications of
      the administration of S. boulardii in immunocompromised patients. For this reason
      the therapeutic usage of probiotics should be carefully considered regarding its
      risk-benefit potential.

PMID- 14648436
TI  - [Episodes of depression with attempted suicide after taking valsartan with
      hydrochlorothiazide].
AB  - HISTORY AND CLINICAL FINDINGS: A 43-year-old woman was admitted after a suicide
      attempt with 1.5 g atenolol. Physical and neurological examination showed no
      abnormality, but psychiatric examination revealed symptoms of a major depression.
      Four weeks prior to admission a valsartan-hydrochlorothiazide combination had
      been added to the antihypertensive medication. INVESTIGATIONS: Laboratory tests,
      electrocardiography, chest-x-ray, electroencephalography and cranial computerised
      tomography showed no abnormality. DIAGNOSIS AND COURSE: The depressive disorder
      resolved within ten days after discontinuation of valsartan and
      hydrochlorothiazide without specific treatment. Blood pressure was normal under
      treatment with metoprolol. CONCLUSION: Depressive drug reactions can produce a
      substantial morbidity. This case of a drug induced affective disorder should
      heighten the awareness of unusual reactions to valsartan-hydrochlorothiazide
      therapy.

PMID- 14648437
TI  - [Confocal laser scanning microscopy: a deep look into the cell].
AB  - Confocal laser scanning microscopy (CLSM) is a powerful technology for assaying
      biomolecular distribution and dynamics in cells and tissues. Innovations in CLSM
      techniques, coupled with the development of new dyes and genetically encoded
      indicators, have increased both in vitro and in vivo imaging approaches. CLSM has
      had wide application in basic science, but little impact so far on medical
      investigations. As a "cutting edge" technology CLSM has proved to be a valuable
      tool in some areas within medical applications including pathology, dermatology,
      ophthalmology and research in various other fields of medicine. This paper gives
      an overview about the wide range of CLSM-applications and shows the enormous
      potential of this technology in medical research and development.

PMID- 14648438
TI  - [Diagnosis and treatment of patients with ischemia of the upper extremities
      caused by a dialysis shunt].

PMID- 14648439
TI  - [Primary prevention of sudden cardiac death].

PMID- 14648440
TI  - [Scientific concepts in clinical medicine].
AB  - The understanding of the scientific basis and the theory of knowledge are
      surprisingly heterogeneous in practical and clinical medicine. It is frequently
      influenced or based on the philosophical theory of critical rationalism founded
      by Sir Karl Popper. Because the theory of knowledge and the understanding of
      scientific truth is the central basis for cautious and good clinical practise it
      is necessary to discuss both points to avoid unscientific auto-immunisation
      against critique in a type of medicine that regards herself as science-based.
      Evidence-based medicine would not be possible without interpretation and
      explanation of existing data into the individual treatment context. Besides an
      inductive or deductive logic the historical and situative side-conditions of the
      gathering of knowledge and of experiments are of central importance for their
      interpretation and their relevance in clinical practice. This historical and
      situative context warrants reflection but must also be paid attention to in the
      reflections on medical ethics.

PMID- 14648441
TI  - [Which hygiene methods must be carried out in norovirus infections?].

PMID- 14648442
TI  - Bloodborne and sexually transmitted infections in drug abusers in the United
      States, Latin America, the Caribbean, and Spain.
AB  - In the United States, approximately 1 million Americans are infected with human
      immunodeficiency virus (HIV), and several thousand new infections are reported
      each year. More than one-third of cases of acquired immunodeficiency syndrome
      (AIDS) are associated with injection drug use. An estimated 1.8 million adults
      and children are currently living with HIV in Latin America and the Caribbean,
      and injection drug abuse remains a major factor in initial exposures to HIV in
      these parts of the world. Although only 3 cases of AIDS related to drug abuse
      have been reported in Bolivia, a country with a nascent epidemic, >19,000 cases
      of AIDS have been reported in Argentina and >22,000 in Brazil, with a significant
      number associated with injection drug use. Extensive epidemiological and clinical
      research has been conducted in the United States and elsewhere to determine the
      extent and nature of the problem and to design and develop interventions
      (prevention and treatment) for drug abusers infected with HIV. The articles in
      this supplement present a current view of the nature and extent of the bloodborne
      and sexually transmitted infections in drug abusers and their partners in the
      Western Hemisphere.

PMID- 14648443
TI  - Epidemiology of human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome in injection drug users in Argentina: high seroprevalence of HIV
      infection.
AB  - The aim of this study was to compile published data and to describe the
      prevalences of human immunodeficiency virus (HIV) infection among injection drug
      users (IDUs) in different populations studied in Argentina from 1987 through
      1999. Twenty-two studies of HIV infection in the IDU population were selected,
      and 6 subject groups were defined: outpatients, prisoners, children in
      rehabilitation institutes, hospitalized patients, IDUs receiving drug treatment,
      and female sex workers. The median prevalence of HIV infection among 1506
      outpatients (5 studies) was 64.0%; among 175 prisoners (1 study), the prevalence
      was 35.4%; among 446 children in rehabilitation institutes (4 studies), the
      prevalence was 48.1%; among 136 hospitalized patients (2 studies), the prevalence
      was 49.5%; among 2708 IDUs receiving drug treatment (7 studies), the prevalence
      was 39.0%; and among 26 female sex workers (2 studies), the prevalence was 47.0%.
      Prevalence of HIV infection was high among IDUs in Argentina, ranging from 27% to
      80%.

PMID- 14648444
TI  - Bloodborne and sexually transmitted infections in drug users in a hospital in
      Buenos Aires, Argentina.
AB  - Injection drug users (IDUs) constitute a population highly vulnerable to
      infections transmitted by blood or sexual relations. Social problems and
      marginalization hinder IDUs from accessing the health care system. The rates of
      prevalence of human immunodeficiency virus, hepatitis C virus, and hepatitis B
      virus infections in IDUs are high, and they have become of great concern for the
      Argentinean health care system. An integral frame oriented to identifying the
      extent of the different individual risk factors, and to enhancing social
      circumstances, has shown a significant benefit in terms of personal and social
      matters. These risk factors were analyzed according to a severity of drug abuse
      scoring system. At the beginning of the study, only 7 of 108 patients were in a
      low gravity stage, whereas there were 40 patients in the low gravity stage by the
      end of the study (P<.0001). On the basis of our results, we conclude that low
      cost nonmedical tools are effective and have a high impact on patients' health.

PMID- 14648445
TI  - High seroprevalence of bloodborne viruses among street-recruited injection drug
      users from Buenos Aires, Argentina.
AB  - Injection drug use is the main mechanism of human immunodeficiency virus (HIV)
      transmission in Argentina (40% of reported AIDS cases in Argentina). This study
      was conducted among street-recruited injection drug users (IDUs) from Buenos
      Aires, with the aim of estimating seroprevalence and coinfection of HIV,
      hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic
      viruses (HTLVs). A total of 174 volunteers participated in this study; 137 were
      men (78.7% of volunteers). The average age of the participants was 30 years. Only
      64 of participants (37%) had no viral infection, whereas 110 (63%) were infected
      with > or =1 viruses. Seroprevalences were 44.3% for HIV, 54.6% for HCV, 42.5%
      for HBV, 2.3% for HTLV-I, and 14.5% for HTLV-II. Among the 77 HIV-infected
      persons, only 6.5% (5 persons) were not coinfected with other viruses; 88.3% (68)
      were coinfected with HCV and 68.8% (53) were coinfected with HBV. We demonstrated
      the existence of multiple viral infections with a high rate of prevalence in IDUs
      in Buenos Aires, Argentina.

PMID- 14648446
TI  - Harm reduction actions as a health care construction process at a public health
      center in Rosario, Argentina.
AB  - Even faced with serious numbers of human immunodeficiency virus (HIV) and other
      infections among injection drug users (IDUs), Argentina lacks large-scale harm
      reduction programs at national, state, and local levels. We describe the strong
      relationship of IDUs with the HIV/acquired immunodeficiency syndrome epidemic in
      Rosario. We discuss a 2-year-long ongoing experience of drug-related harm
      reduction actions developed at a public health center, which began as a response
      to a spontaneous demand for needles and syringes and became a permanent and
      sustainable set of health actions for a group of nearly 50 IDUs, a larger number
      of drug users who do not inject, and their contacts. These actions comprise
      voluntary testing and counseling for HIV and other infections, reproductive
      counseling, condom promotion and distribution, and needle and syringe
      distribution without needle exchange. This experience, amenable to replication,
      shows that public health teams can engage successfully in harm reduction actions.

PMID- 14648447
TI  - Vulnerable among the vulnerable: drug users in situations of poverty and
      indigence in Argentina.
AB  - To study drug use in the context of poverty, it is necessary to undertake a
      complex analysis of various perspectives to understand the dense interweaving of
      socioeconomic, political, and cultural factors involved in the problem. The
      analysis of this social scenario was our starting point in planning holistic
      actions for the prevention of human immunodeficiency virus/acquired
      immunodeficiency syndrome and other illnesses related to drug use. Merely copying
      successful models from developed countries, which are designed for other contexts
      and populations, would result in insufficient and ineffective actions. The
      Asociacion Civil Cristiana Recuperacion Atencion de Drogadependientes (ACCRAD),
      also known as "El Retono" ("sprout"), is a nongovernmental organization that has
      been working since 1985 to consolidate a model of analysis and intervention that
      considers this complex framework and seeks to meet the needs of drug users from
      the poorest sectors of society. Our research on the use of drugs and its
      relationship to poverty, together with the documentation of harm-reduction
      interventions, has been carried out since 1997.

PMID- 14648448
TI  - Human immunodeficiency virus/acquired immunodeficiency syndrome prevention in
      injection drug users and their partners and children: lessons learned in Latin
      America--the Argentinean case.
AB  - Thirty-nine percent of Argentineans living with acquired immunodeficiency
      syndrome were infected with human immunodeficiency virus through the injection of
      drugs. However, it was not until the 1990s that harm reduction programs were
      created. Research and outreach projects have been developed to identify and
      interact with the hidden injection drug user (IDU) population. Implementation of
      rapid assessment and response methodology contributed to the founding of
      Argentina's first syringe exchange program. Community-based outreach is the
      appropriate method for working with the impoverished population of Buenos Aires.
      Seroprevalence studies and focused prevention campaigns targeting IDUs and their
      sex partners and children have been developed. Collaborations between government
      and nongovernmental organizations in various cities supported the distribution of
      prevention and harm reduction messages to 900 IDUs within a 3-month period.
      Ongoing research, community-based interventions, and collaborative work among
      different organizations allow for more frequent and more consistent contact with
      the IDU population of Argentina.

PMID- 14648449
TI  - Drug use, harm reduction, and health policies in Argentina: obstacles and new
      perspectives.
AB  - High human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)
      incidence among injection drug users (IDUs) shows the failure of traditional
      health policies. The preference of IDUs for injected cocaine exposes them to high
      risks for contracting HIV because of the frequency of drug use. The correlation
      of poverty with the selling of drugs, especially the so-called "drugs of poverty"
      -freebase cocaine and crack--is a consequence of prohibitions against drug use
      and of urban unemployment. In Argentina, "zero-tolerance" approaches and
      punishment for personal drug use tend to exclude IDUs from the country's health
      care system. A historical perspective is presented regarding approaches to the
      prevention of HIV/AIDS and harm reduction in Latin America and Argentina, where,
      despite isolated efforts, IDUs had no free access to sterile needles until the
      end of the 1990s. We present the impact of programs and campaigns of the
      Argentinean Harm Reduction Association, showing how and why, even with obstacles,
      harm reduction is possible and necessary.

PMID- 14648450
TI  - Obstacles to the development of prevention and public health policies in
      Argentina.
AB  - The spread of the human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome (AIDS) epidemic and its impact in the injection drug user population
      occurred while the social assistance of the State diminished and poverty
      increased within the Argentinean population. Five main obstacles have been
      identified for the development of HIV infection/AIDS prevention policies for
      injection drug users: the scarce development of research and its poor impact in
      the definition of governmental policies, the characteristics of the legal
      framework regarding illegal drug use, the orientation of the health and social
      care services directed to drug users, deficiencies in the training of technicians
      and professionals related to these issues, and problems in assigning existing
      resources. International agencies play a very important role in this context. The
      project "Prevention of HIV Infection in Injection Drug Users in the Southern
      Cone," financially supported by the Joint United Nations Programme on HIV/AIDS
      and the United Nations Office on Drugs and Crime, is presented as an example.

PMID- 14648451
TI  - The dynamics of the human immunodeficiency virus epidemics in the south of
      Brazil: increasing role of injection drug users.
AB  - Changes in human immunodeficiency virus (HIV) infection among injection drug
      users (IDUs) are provoking a shift in the pattern of the HIV/AIDS epidemic in
      some regions of Brazil. IDUs living in 2 cities (Porto Alegre and Itajai) in
      southern Brazil were contacted, interviewed, and tested for HIV. In 1998, 187
      IDUs were surveyed and, in 2000, 352 IDUs. In Porto Alegre, HIV seroprevalence,
      age, and duration of injection history increased significantly over time. In
      contrast, a trend toward decline was observed in Itajai. Homelessness,
      joblessness, and prison incarceration, as well as lifetime needle sharing, also
      increased over time in Porto Alegre. At the time of the study, at both sites,
      rates of needle sharing and condom use were similar, but use of syringe exchange
      programs, health and drug treatment, and HIV testing had increased over time.
      IDUs living in southern Brazil are at increased risk of HIV infection, indicating
      the continued need for permanent surveillance and preventive strategies.

PMID- 14648452
TI  - Brazilian response to the human immunodeficiency virus/acquired immunodeficiency
      syndrome epidemic among injection drug users.
AB  - The Brazilian response to the human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) epidemic is being observed all over the world
      because of its success. Understanding the role of injection drug users (IDUs) in
      the epidemic and the political response thereto is a key factor in the control of
      the epidemic in Brazil. This paper summarizes some of the most important analyses
      of the Brazilian response to the HIV/AIDS epidemic among and from IDUs. Key
      elements of the response include the support of the Brazilian Universal Public
      Health System, the provision of universal access to highly active antiretroviral
      therapy, and the creation of harm reduction projects that are politically and
      financially supported by the federal government. The response among and from IDUs
      is a key element in overall control of the HIV/AIDS epidemic. The response to the
      epidemic among and from IDUs has been headed in the correct direction since its
      beginning and is now being intensively expanded.

PMID- 14648453
TI  - Case management of human immunodeficiency virus-infected injection drug users: a
      case study in Rio de Janeiro, Brazil.
AB  - The provision of care and support to persons living with human immunodeficiency
      virus (HIV) in Brazil who also use drugs and/or alcohol represents special
      challenges because of the combined effects of addiction, poverty, stigma, and
      discrimination. This paper presents details on a program providing both clinic-
      and field-based care to HIV-infected injection drug users, highlighting the use
      of a specialized case management approach to address the clinical and
      psychosocial needs of this population. This program includes both a mobile case
      management team that fosters group discussions and provides individual
      counseling, and provision of medical consultations at 2 major drug treatment
      centers in Rio de Janeiro. The article also describes the experience of working
      with injection drug users who regularly attend an outpatient clinic serving
      marginalized communities through the use of mutual self-help groups and
      specialized support groups to address to issue of adherence to antiretroviral
      therapies for the treatment of HIV/acquired immunodeficiency syndrome.

PMID- 14648454
TI  - Determinants of health care use among Puerto Rican drug users in Puerto Rico and
      New York City.
AB  - This study was conducted to identify factors accounting for differences in health
      care and drug treatment utilization between Puerto Rican drug users residing in 2
      separate locations. Survey findings from 334 drug users in Puerto Rico and 617 in
      New York City showed that those in Puerto Rico were 6 times less likely than
      their counterparts in New York to have used inpatient medical services and 13 to
      14 times less likely to have used outpatient medical services or methadone. They
      also were less likely to have health insurance or past drug treatment. After site
      was controlled for, health insurance and previous use of physical or mental
      health services remained significant predictors of health care and drug treatment
      utilization during the study period. Although Puerto Rican drug users in Puerto
      Rico are not an ethnic minority, they reported significant disparities in health
      services use compared with Puerto Rican drug users in New York.

PMID- 14648455
TI  - Trends in human immunodeficiency virus infection among drug users in a
      detoxification unit.
AB  - In a cross-sectional study of 1111 injection drug users (IDUs) admitted to a
      hospital detoxification unit between 1987 and 2001, characteristics of substance
      abuse and blood samples were obtained at study entry. The median age at admission
      was 27 years, the median age at first injection of drugs was 19 years, and the
      median duration of injection drug use was 84 months. Overall prevalence of human
      immunodeficiency virus (HIV) infection was 60% (58% in men, 66% in women;
      P=.026). Age at start of and duration of injection drug use were associated with
      HIV infection (P<.001). The rate of HIV infection in persons with short duration
      of drug use (<24 months) was higher among women (45%) than among men (21%)
      (P=.002). The prevalence of HIV infection among IDUs <21 years old at first use
      of injection drugs and among patients reporting <48 months of injection drug use
      was significantly lower in those who started injection drug use after 1992 (19%
      vs. 53% of IDUs; odds ratio, 4.42; 95% confidence interval, 1.80-10.85).
      Awareness of acquired immunodeficiency syndrome, preventive measures, and
      substance abuse treatment have contributed to the stabilization of the HIV
      epidemic. The higher prevalence of HIV infection among women IDUs and among young
      IDUs who recently began injecting drugs emphasizes the need to target HIV
      transmission risk reduction interventions early.

PMID- 14648456
TI  - Lessons from the history of the human immunodeficiency virus/acquired
      immunodeficiency syndrome epidemic among Spanish drug injectors.
AB  - In Spain, approximately 10 years passed between the time when human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) harm
      reduction programs should have been developed with sufficient coverage to have an
      optimum impact on public health (before the HIV/AIDS epidemic's explosion in
      1984) and the date of their actual implementation. This delay yielded an enormous
      cost for the country. The introduction of the virus in drug injector networks
      during a period of widespread diffusion of heroin injection and the lack of
      political awareness of the growing problem were 2 important factors that
      contributed to the important diffusion of the HIV infection among Spanish
      injection drug users. Lessons can be learned that may be of great interest in
      countries or territories facing similar challenges now and in the future.

PMID- 14648457
TI  - Cognitive and behavioral change in health care professionals after training in
      the treatment of injection drug users.
AB  - A training program was implemented for 56 health care professionals who work with
      injection drug users (IDUs) in Spain. The aims were to change health care
      professionals' concepts of drug treatment for IDUs and increase the knowledge
      required to implement effective drug treatment programs and train professionals
      who would in turn train other professionals, thus creating a network. Follow-up
      was carried out at 8 months. All of the professionals had little prior experience
      in designing and implementing risk reduction programs. At the end of the training
      program, all thought that they had increased their knowledge; had gained the
      skills required to design, implement, and evaluate harm reduction programs for
      IDUs; and felt qualified to train colleagues from other treatment centers. After
      1 year, they had trained 676 health care professionals. The program is
      appropriate with regard to the aims sought and the target population for which it
      was designed. The effectiveness of a network-building strategy was also
      validated.

PMID- 14648458
TI  - The challenge of implementation of preventive programs in a developing country:
      experiences, situations, and perspectives in Uruguay.
AB  - In recent years, Uruguay has seen an alarming increase in the percentage of
      persons with human immunodeficiency virus infection/acquired immunodeficiency
      syndrome who are injection drug users (IDUs) and their sex partners, which has
      consequently contributed to the rate of perinatal transmission. Development of
      preventive harm reduction and risk reduction strategies has become imperative.
      These strategies must be suitable for a developing country and focused on its
      population of IDUs. These strategies must include, as a preliminary step, a
      comprehensive analysis of the current local legal system and knowledge about the
      kinds of drugs used, the ways in which they are used, and their effects on public
      health. The conclusions of some studies and a pilot program that Institute of
      Social Research and Development, Instituto de Investigacion y Desarrollo Social,
      Uruguay, implemented in 2001 have pointed to new avenues for the control of the
      epidemic spread among IDUs and to their social environment.

PMID- 14648459
TI  - Retinoids and drugs of abuse: implications for neurological disease risk in human
      immunodeficiency virus type 1 infection.
AB  - Among injection drug users, human immunodeficiency virus (HIV) type 1 infection
      may be associated with an increased risk of nervous system disease. For HIV
      infected drug users with vitamin A deficiency, the overall risk of HIV-related
      morbidity and mortality may also be higher. In previous studies, levels of
      retinol, retinol-binding protein, and transthyretin in samples from such
      individuals were examined and found to be lower than such levels in seronegative
      control subjects. Also, in studies using an activated mononuclear cell line, all
      trans retinoic acid and 9-cis retinoic acid suppressed production of the tumor
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma. However, simultaneous
      exposure of the cells to morphine at a concentration similar to that to which
      drug users are exposed resulted in increased production of these cytokines.
      Therefore, morphine may alter the immunomodulatory effects of retinoids, thereby
      potentially affecting the clinical outcome of studies involving retinoid
      administration to HIV-infected drug users and increasing the risk for the
      development of HIV-related complications, including neurological disease.

PMID- 14648460
TI  - Protecting oneself from human immunodeficiency virus: are prevention messages
      being heard?
AB  - The transmission of human immunodeficiency virus (HIV) and other communicable
      diseases is socially organized. Public health attempts to reduce HIV transmission
      have admonished persons to reduce their risks--in effect, to act as if their
      partners are or could be HIV-seropositive. Therefore, a good test of the
      effectiveness of public health messages is to compare the riskiness of behaviors
      among HIV-seronegative persons with the riskiness of the behavior of
      serodiscordant partners. Data were collected for a network study of 267 drug
      users and nonusers in an urban inner city. Results show that in most of the
      domains studied, persons with HIV-seronegative partners engaged in less risky
      behavior than did persons whose partners were HIV-seropositive. This result
      suggests that risk reduction messages have been relatively successful in
      convincing most persons to treat their partner as if he or she were HIV
      seropositive.

PMID- 14648461
TI  - Health services research: drug use and human immunodeficiency virus in the United
      States.
AB  - Major research findings show gaps in health services research on the prevalence
      and outcomes of patient- and organization-level human immunodeficiency virus
      (HIV) and drug abuse prevention and treatment services. The latest thrust of
      health services research on translational research issues includes informing and
      training practitioners about new, proven drug abuse treatment interventions;
      changing treatment organizations (creating a climate for change and building a
      culture to sustain change); and financing new treatments. Findings defining the
      direct relationship between the quality of drug abuse treatment and the patients'
      program completion, the perception of the staff by the patient, feelings of self
      empowerment and mitigation of patient and organizational readiness, the
      superiority of integrated care, and the primary reasons for delays in HIV
      infected substance-using patients seeking care are included. More needs to be
      done to increase the participation of substance abuse programs in teaching about
      and implementing HIV prevention and developing means to modulate or eliminate
      barriers to the integration of HIV and substance abuse care.

PMID- 14648462
TI  - Drug-using women need comprehensive sexual risk reduction interventions.
AB  - In the United States, drug users have dramatically reduced drug-related risk
      behaviors but continue sexual behaviors that place them at risk for human
      immunodeficiency virus (HIV) infection. Successful interventions are likely to be
      those that intervene at multiple levels, yet, historically, sexual interventions
      for drug users have primarily addressed only personal factors, such as condom
      use. Sexual risk arises from personal factors (e.g., perceived vulnerability and
      protective behaviors); interpersonal factors (e.g., relationship type and a
      partner's risk profile); social factors (e.g., gender roles and sexual mixing
      patterns among and between networks); and, finally, community-level factors
      (e.g., access to preventive methods and the prevalence of a sexually transmitted
      pathogen within a network). For female drug users, multiple sources of risk plus
      concurrent drug use during sex pose additional prevention challenges that
      disproportionately elevate their risk of sexually acquired HIV infection. New,
      multimodal interventions need to be developed and tested to more effectively
      address the many sources of sexual risk facing female drug users.

PMID- 14648463
TI  - Human immunodeficiency virus prevention and the potential of drug abuse
      treatment.
AB  - Since first recognition of the scope of the acquired immunodeficiency syndrome
      epidemic among the drug-using community, substance abuse treatment has been
      viewed as playing an important role in preventing new infections. In the past 20
      years, many studies have documented significantly lower rates of drug use, drug
      related risk behaviors, and human immunodeficiency virus (HIV) infections among
      drug users who remain in treatment programs. There is also growing evidence that
      drug detoxification alone is insufficient to provide protection from HIV
      infection. These findings have important implications for users of cocaine and
      noninjection drugs, as well as heroin injectors. Despite strong evidence of
      effectiveness and widespread support for the important public health role of drug
      treatment, its impact has been compromised by limited availability and
      acceptability. The available data clearly establish drug abuse treatment as HIV
      prevention, yet without expansion of existing treatment programs and the
      continued development of treatments for addiction to cocaine and other widely
      used stimulants, its public health potential cannot be realized.

PMID- 14648464
TI  - Effects of long-term, medically supervised, drug-free treatment and methadone
      maintenance treatment on drug users' emergency department use and
      hospitalization.
AB  - We examined the effect of drug treatment in 1996 on repeated (> or =2) emergency
      department visits and hospitalization in 1997 in a cohort of New York State
      Medicaid-enrolled human immunodeficiency virus (HIV)-positive and HIV-negative
      drug users. In HIV-positive drug users, the adjusted odds of repeated emergency
      department visits were increased for those receiving no long-term treatment (odds
      ratio [OR], 1.65; 95% confidence interval [CI], 1.04-2.75), whereas the adjusted
      odds for those receiving methadone treatment and those receiving drug-free
      treatment for > or =6 months did not differ. The adjusted odds of hospitalization
      in the HIV-positive group were higher for those receiving long-term methadone
      treatment (OR, 1.69; 95% CI, 1.14-2.55) and for those receiving no long-term
      treatment (OR, 1.91; 95% CI, 1.29-2.88), compared with those receiving drug-free
      treatment. In the HIV-negative group, these associations were similar but weaker.
      For both HIV-positive and HIV-negative drug users, long-term drug-free treatment
      was at least as effective as long-term methadone treatment in reducing use of
      services indicative of poorer access to care and/or poorer health.

PMID- 14648465
TI  - Adherence to heroin dependence therapies and human immunodeficiency
      virus/acquired immunodeficiency syndrome infection rates among drug abusers.
AB  - Adherence is a primary determinant of treatment effectiveness; thus, poor
      adherence attenuates optimum clinical benefit. A bibliographic review was
      conducted to evaluate the impact of adherence to heroin dependence treatment on
      human immunodeficiency virus (HIV) transmission and to identify interventions
      proven to be effective in improving adherence. The best adherence rates were
      achieved by methadone and diacetylmorphine, both of which are comparable in
      promoting significant reduction in heroin use. Methadone adjusted-dose studies
      with daily doses ranging from 100 to 200 mg and multiple support interventions
      achieved the highest adherence rates. Studies of methadone maintenance that
      examined changes in HIV prevalence of infection have found that higher treatment
      adherence is correlated with a reduction in HIV transmission. These data suggest
      that patients who adhere continuously to methadone treatment are less likely to
      continue injecting illicit drugs and sharing contaminated injection equipment
      than are those who interrupt treatment, thus preventing the spread of HIV via
      drug injection.

PMID- 14648466
TI  - [I remember revisions to bioethics laws].

PMID- 14648467
TI  - [Channel].

PMID- 14648468
TI  - [Antimicrobial peptides as efficient DNA vectors].

PMID- 14648469
TI  - [Canine adenovirus: useful for gene transfer in humans?].

PMID- 14648470
TI  - [Predicting metastatic potential: genetic markers].

PMID- 14648471
TI  - [Targeted molecular therapy: the example of Iressa (ZD1839)].

PMID- 14648472
TI  - [Are mitotic spindles a cellular sensory organ?].

PMID- 14648473
TI  - [A rare genetic disease: multiple sulfatase deficiency].

PMID- 14648474
TI  - [Biosynthesis of hydrocortisone in yeast].

PMID- 14648475
TI  - [Patched is a dependence receptor].

PMID- 14648476
TI  - [Conservative molecular mechanisms controlling cell polarity].

PMID- 14648477
TI  - [Development of a pseudogene with a functional role].

PMID- 14648478
TI  - [A fatal kiss between estrogen receptor and dioxin].

PMID- 14648479
TI  - [Genetics of autism: from genome scans to candidate genes].
AB  - The autistic disorder was firstly described by Leo Kanner sixty years ago. This
      complex developmental disability is characterized by social and communicative
      impairments and repetitive and stereotyped behaviours and interests. The
      prevalence of autism in the general population is about 1 in 1,000, with four
      males affected for one female. In approximately 15% of the cases, autism is
      associated with known genetic disorders, such as fragile X syndrome, tuberous
      sclerosis or Rett syndrome. Nevertheless, a recognised medical etiology can only
      be identified in a minority of cases. A higher recurrence risk in families with
      autistic subjects (45 times greater than the prevalence in the general
      population) and higher concordance for autism among monozygotic (60-90%) than
      dizygotic (0-10%) twins argue for a genetic predisposition to idiopathic autism.
      The past decade has been marked by an increased interest in the genetic basis of
      autism, with a series of multiple independent whole genome scans and chromosomal
      abnormalities studies. These analyses have pointed out several candidate regions
      on chromosomes 2q, 7q, 6q, 15q and sex chromosomes. These regions possess
      candidate genes that have been screened for mutations or association with autism.
      However, a clear involvement of a major susceptibility gene (or genes) in autism
      remains far from clear. The results from linkage studies and the clear drop in
      the concordance rates between monozygotic and dizygotic twins suggests that the
      genetic aetiology of autism is certainly heterogeneous (different genes in
      different families) and polygenic (more than one affected gene per individual).
      The almost finished sequence of the human genome and the generation of haplotype
      maps will shed light on the inter-individual genetic variability and will
      certainly increase the power and reliability of association studies for complex
      traits, such as autism.

PMID- 14648480
TI  - [Bradykinin receptors: towards new pathophysiological roles].
AB  - In addition to being a pro-inflammatory mediator, bradykinin is now recognized as
      a neuromediator and regulator of several vascular and renal functions. New
      breakthroughs point to unusual and atypical signalling pathways for a G-protein
      coupled receptor that could explain the anti-proliferative and anti-fibrogenic
      effects of bradykinin. The availability of transgenic and knock out animal models
      for bradykinin receptors or bradykinin-synthesizing or -catabolic enzymes
      confirms these cardiac and renal protective roles for this peptide system.
      Bradykinin receptors are involved in the therapeutic action of angiotensin-1
      converting enzyme inhibitors that are used in the treatment of arterial
      hypertension, heart failure and diabetes. Nevertheless, recent evidence
      highlights dissimilar mechanisms in the regulation and function of these
      receptors between the central nervous system and peripheral tissues. Therefore,
      the development of more specific bradykinin receptor agonists or antagonists
      devoid of central actions seems to evolve as a new therapeutic approach.

PMID- 14648481
TI  - [Functional duality of kinin receptors in pathophysiology].
AB  - Kinins are autacoid peptides and central neuromediators involved in
      cardiovascular regulation, inflammation and pain. Their effects are mediated by
      two transmembrane G-protein-coupled receptors denoted as B1 and B2. While the B2
      receptor is constitutive, the B1 receptor is inducible and up-regulated in the
      presence of cytokines, endotoxins or during tissue injury. The B2 receptor is
      believed to play an important role in the beneficial effects of angiotensin-1
      converting enzyme inhibitors used in the treatment of cardiovascular diseases,
      yet it is involved in the acute phase of inflammation and of somatic and visceral
      pain. Conversely, the B1 receptor participates in the chronic phase of these
      responses and is likely to play a strategic role in diseases with a strong immune
      component such as rheumatoid arthritis, multiple sclerosis, septic shock and
      diabetes. A dual function for the B1 receptor is also reported in some
      pathologies in which it can exert either a protective (multiple sclerosis and
      septic shock) or harmful (pain and inflammation) effect. Therefore, the use of
      antagonists for these receptors as clinical therapeutic agents requires a
      rigorous evaluation of the potential side effects.

PMID- 14648482
TI  - [The human placenta and its pathologies: focus on oxygen].
AB  - At the time of placentation, the conceptus surrounds itself with a trophoblastic
      layer where the villous tree develops and the uteroplacental circulation takes
      place. Analysis of the modalities of maternal blood entrance demonstrated a
      physiological hypoxia ending with the first trimester of pregnancy. Moreover,
      cultures of first trimester villous explants have shown the role of oxygen in
      extravillous cytotrophoblast proliferation, decidual invasion and spiral artery
      remodeling. Oxygen appears to be a key factor controlling the mechanism of
      placentation by regulating the transcription of several genes, such as VEGF
      (vascular endothelial growth factor), leptin, etc. These genes are turned on or
      off as a function of oxygen partial pressure via an oxygen sensor. Oxygen is now
      considered to be implicated in the development of several pathologies of
      pregnancy. It is involved at different steps in the cascade of events leading to
      preeclampsia. Positive correlations have been observed between oxygen partial
      pressure and abnormal development of the villous tree in intrauterine growth
      retardation, and in maternal anemia or pregnancy in altitude.

PMID- 14648483
TI  - [Negative cross-talk between nuclear receptors and transcription factors:
      implications in inflammation and oncogenesis].
AB  - Nuclear receptors are transcription factors mediating a signal pathway that
      triggers the cell into differentiation. By contrast, membrane receptors mediate a
      proliferation signal pathway via a phosphorylation cascade that activates
      transcription factors such as NF-kappa B and AP-1 complex. To allow efficient
      cellular integration of these contradictory signals, transcription factors
      mutually interact and modulate their transcription activity. Although often
      synergistic, these interactions can also be negative. They then result from
      various mechanisms acting either at the transcriptional level (competitive
      binding to DNA or to a common limitant cofactor...) or upstream DNA binding
      (inhibition of DNA binding, inhibition of phosphorylation...). Whatever the
      precise mechanisms, these negative interactions are significant in vivo. For
      instance, glucocorticoid and PPAR receptors repress the transcription activity of
      the pro-inflammatory factor NF-kappa B. This partly explains the anti
      inflammatory effects of their respective ligands (glucocorticoids and fibrates).
      Likewise, interactions between nuclear receptors and AP-1 complex are likely to
      participate to the anti-oncogenic activity of glucocorticoids and retinoic acid.

PMID- 14648484
TI  - [Bacterial cyclostatin, or how do bacteria manipulate the eukaryotic cell cycle].
AB  - Several bacterial proteins have been recently described that share the ability to
      inhibit the proliferation of cells in culture without causing early signs of
      cytotoxicity. Such observations suggest the existence of bacterial mechanisms of
      control of the eukaryotic cell cycle contributing to pathogenicity or adaptation
      to the host. This emerging concept of cellular microbiology is critically
      analyzed considering as a model the cytolethal distending toxins (CDT), a family
      of toxins whose mode of action on the cell cycle has been thoroughly studied over
      the last few years. CDTs activate a physiological G2 checkpoint in exposed cells,
      probably from an initial DNA alteration whose precise molecular nature has not
      yet been determined. Experimental data are lacking to extrapolate in vivo the
      antiproliferative effect of these bacterial proteins that we tentatively propose
      to call cyclostatins.

PMID- 14648485
TI  - [Nucleosome differentiation: role of histone H2A variants].
AB  - The histones H2A, H2B, H3 and H4 are very conserved basic proteins that wrap
      almost two turns of DNA to form the nucleosome core. Conventional histones can be
      replaced with histone variants that are found in all eukaryotic organisms.
      Together with other nucleosome modification pathways, histone variants
      participate in the functional specialization of chromatin. In this review, we
      focus on three major H2A histone variants: H2A.X, H2A.Z and macroH2A. Recent
      discoveries highlight their involvement in crucial events such as DNA repair and
      transcriptional regulation.

PMID- 14648486
TI  - [Issues addressed by tuberculosis in France in 2003].
AB  - The incidence of tuberculosis in France has not declined since 4 years. In fact,
      there is a constant decline in the whole country but a slight increase in the
      Paris region. As in other big cities in the world, the recent increase in cases
      in Paris is mainly due to immigrants. In contrast, HIV coinfection accounts for a
      small and decreasing part of the cases. Moreover, the rates of resistance and
      multiresistance to antituberculous drugs are low and stable indicating that the
      treatment of active diseases is satisfactory. The respective part of cases due
      either to primary infections or to reactivations is unknown. In order to control
      tuberculosis in Paris, we need to implement better infection control policy with
      active screening of contacts of patients with active tuberculosis as well as
      treatment of latent tuberculosis infections.

PMID- 14648487
TI  - [Autism: toward a necessary cultural revolution].
AB  - Autism is a pervasive developmental disorder of childhood characterised by
      disturbances in both social interactions and communication as well as stereotyped
      patterns of activities and behaviour. The increase in estimates of the prevalence
      of autism has raised the question of an "epidemic" of autism. More active case
      assessment and changes in diagnostic criteria probably account in large part for
      such increase. Investigators have attempted to define the neural pathophysiology
      of autism ever since the hypothesis of "refrigerator mother" as its cause was
      replaced by the view that it is a developmental disorder of the immature brain.
      However consensus is yet to be reached concerning the brain regions implicated.
      Psychoanalysis, cognitive psychology, neurophysiology, neuropharmacology, and
      genetics propose restricted view of the major issues leaving extensive areas
      unexplored. Therapeutic approaches induce only partial and uncertain results.
      There is no cure for autism but substantial evidence indicates that early,
      intensive, individualised education is beneficial for children. All modern
      intervention programs for autism affected children share a high degree of
      environmental structuring and predictability and an extensive individual
      approach. Autism being a behaviourally defined syndrome, it gave rise to a number
      of controversies concerning definition, classification, etiopathogenesis and
      therapeutics. In the 1990s a crisis has occurred in France with a loss of
      confidence between parents and psychiatrists with a problem concerning the means
      and ways of care of the autistic individual. The aim of this paper is to point
      out the different questions raised by autism in order to better understand this
      syndrome which touches upon essential behaviour-related aspects such as self
      consciousness, reality perception, the functioning of the thought and
      communication, as well as the role of hereditary and acquired influences in
      normal and pathological development.

PMID- 14648488
TI  - [SARS-CoV: 2. Modeling SARS epidemic].

PMID- 14648489
TI  - The future of the North American Veterinary Teaching Hospital.

PMID- 14648490
TI  - Veterinary medicine: a profession or a business?

PMID- 14648491
TI  - Curriculum development at Cambridge Veterinary School.

PMID- 14648492
TI  - The Royal Veterinary College, London.

PMID- 14648493
TI  - The BVM and S at the University of Edinburgh.

PMID- 14648494
TI  - Learning and teaching innovations in the veterinary undergraduate curriculum at
      Glasgow.

PMID- 14648495
TI  - Problem-solving concepts and theories.
AB  - Many educators, especially those involved in professional curricula, are
      interested in problem solving and in how to support students' development into
      successful problem solvers. The following article serves as an overview of
      educational research on problem solving. Several concepts are defined and the
      transition from one theory to another is discussed. Educational theories
      describing problem solving in the context of behavioral, cognitive, and
      information-processing pedagogy are discussed. The final section of the article
      describes prior findings regarding expert-novice differences in problem solving
      of various kinds.

PMID- 14648496
TI  - Research in medical problem solving: a review.
AB  - This article is a review of problem-solving models that have been studied in the
      medical domain. These models seek to describe and evaluate the cognitive
      processes activated in problem solving in the medical domain and to use this
      knowledge to further evaluate expert-novice differences. The principle models
      discussed are the hypothetico-deductive, illness scripts, and the probabilistic.
      After reviewing these problem-solving models, the reasoning strategies identified
      in medical problem solving will be discussed. These strategies, forward-backward
      and broad-narrow, are analyzed as indicators of expert versus novice problem
      solving in the medical domain. Finally, the methods identified for studying
      medical problem solving-simulated patients, stimulated recall, think-aloud
      protocol, and the Pathfinder algorithm-will be discussed.

PMID- 14648497
TI  - Cognitive processes of second-year veterinary students in clinical case
      resolution.
AB  - Researchers have established a general understanding of the cognitive processes
      of individuals and have identified expert and novice problem-solving differences.
      This study was directed towards an evaluation of the problem-solving abilities of
      a cohort of students completing their second year of veterinary study in a
      primarily lecture-based curriculum. Problem-solving abilities were evaluated by
      analysis of an audiotaped think aloud of students resolving a clinical case that
      was progressively disclosed. Transcripts of the articulated thoughts were
      analyzed using a novel taxonomy to understand the problem-solving process used by
      the students. Although all students were at the same level of training, a variety
      of problem-solving strategies were identified. Comparison to prior research
      revealed that the students exhibited characteristics consistent with novice
      problem solvers when faced with ill-defined problems, though no single,
      consistent pattern was evident.

PMID- 14648498
TI  - Are the concepts of andragogy and pedagogy relevant to veterinary undergraduate
      teaching?
AB  - Knowles and colleagues have described teaching methods as being either teacher
      centered, with dependent learning (pedagogy), or learner centered, with
      independent learning underpinned by the learners' experience and intrinsic
      motivation (andragogy). This paper argues that both models can be recognized
      within veterinary undergraduate programs. Veterinary students enter the program
      with a high level of intrinsic motivation and are prepared to invest considerably
      in comprehending the material that is presented to them. While this should result
      in learners whose behavior fits the assumptions underlying andragogy, information
      overload, poor communication of the relevance of material, teaching by
      transmission, and examination by memorization often confine learning to the
      dependent learning characteristic of pedagogical approaches. Students' experience
      and practical ability should develop as they progress through the program.
      Drawing upon experience provides opportunities for both fleshing out and putting
      in context the declarative knowledge from the didactic components of the
      curriculum. Where this is achieved (either in the clinical or preclinical
      curriculum), students' motivation and interest is stimulated, resulting in
      andragogical responses of enhanced motivation and engagement with the subject.
      Pedagogy and andragogy can, however, be complementary, rather than antithetical.
      Students enter a new subject with minimal experience and little knowledge about
      it, so a pedagogical methodology may be the most efficient way of initiating
      understanding. However, as understanding develops, an andragogical method becomes
      more appropriate, progressively developing students' independence of learning.
      The cycle may repeat itself during the program, with the balance changing along
      with changes in knowledge, goals, experience, and context.

PMID- 14648499
TI  - Search for the woolly mammoth: a case study in inquiry-based learning.

PMID- 14648500
TI  - Outcome-based education.
AB  - The move to outcome-based education has been one of the most important trends in
      health-profession education in recent years. This paper defines outcomes and
      outcome-based education, describes the development of outcome-based education,
      identifies several different ways that outcomes have been presented, and
      discusses the advantages and disadvantages of the outcome-based educational
      approach. The implementation of outcome-based education at the University of
      Dundee medical school, Scotland, UK is described as a case study for curriculum
      planners in veterinary medical education. The lessons learned in Dundee from six
      years' experience with outcome-based education are identified to aid veterinary
      medical educators wishing to implement the approach.

PMID- 14648501
TI  - Radiology as a tool for teaching veterinary anatomy.
AB  - Instructors at the Ontario Veterinary College (OVC) have a long-standing
      commitment to the use of radiographic films in teaching introductory anatomy in
      the DVM program. The imaging component of the course has evolved from being
      heavily instructor-dependent, with small group teaching in each laboratory
      session, to being almost self-taught. The manner in which recognition of
      structures in radiographic images is examined has also changed. In 2001 a novel
      examination process was introduced. Here we report the approach to the teaching
      and examining of anatomy by use of radiographic images implemented for phase 1 of
      the new DVM curriculum at the University of Guelph.

PMID- 14648502
TI  - An alternative model for teaching emergency procedures.
AB  - Emergency/critical care is a new veterinary specialty that poses special
      challenges in veterinary education. Traditional methods of teaching emergency
      procedures in the teaching hospital place novices in a high-stress, high-stakes
      environment not conducive to learning or to optimum patient care. Our innovative
      emergency-procedures laboratory enables students to acquire a high degree of
      proficiency, in a realistic setting, with focused, controlled instruction and
      practice, replicable in schools with or without emergency/critical care
      facilities.

PMID- 14648503
TI  - Methods and characteristics used in resident selection within the American
      College of Veterinary Ophthalmologists.
AB  - A survey of Diplomates from the American College of Veterinary Ophthalmologists,
      which trains residents, confirms that subjective criteria are most commonly used
      in selecting new residents. The ophthalmologist(s) who oversee(s) the training
      was/were primarily responsible for resident selection. In general, Diplomates
      seemed to be searching for a resident who was intelligent, could communicate
      well, was hard working, and had good interpersonal skills. The most important
      part of an application was the letters of recommendation, with the most important
      consideration being how well the person doing the selecting knew the author of a
      letter. The current process of resident selection does result in a majority of
      residents' completing their programs and ultimately becoming Diplomates of the
      American College of Veterinary Ophthalmologists.

PMID- 14648504
TI  - National workshop on core competencies for success in the veterinary profession.
AB  - A workshop was designed to (1) present results of the Core Competencies for
      Veterinary Medicine project conducted by Personnel Decisions International (PDI);
      (2) discuss and analyze the implications of the PDI study results for academia,
      private practice, and industry; (3) identify actionable items-discuss
      opportunities and barriers; and (4) develop appropriate recommendations-devise
      specific actions for implementation as next steps. In total, 25 veterinary
      colleges were represented at the workshop and a total of 110 attendees
      participated, a broad cross-section of the veterinary profession (both academic
      and non-academic). Through an orchestrated combination of general sessions and
      facilitated, small group discussions, prioritized recommendations for
      implementation and initial action plans for next steps were developed.
      Recommendations included publicizing results of the PDI study, reconsidering
      current admissions policies and processes, evaluating the applicant pool and
      current recruitment programs, developing structured mentoring programs, enhancing
      DVM/VMD training programs, coordinating the development of continuing education
      programs, and overcoming existing barriers to change. Next steps should involve
      collaborative efforts across all sectors of the veterinary profession to develop
      plans for implementing the workshop's recommendations. Leadership for follow-up
      might reasonably come from the Association of American Veterinary Medical
      Colleges (AAVMC), the American Veterinary Medical Association (AVMA), and the
      American Animal Hospital Association (AAHA), either individually or collectively,
      through the National Commission on Veterinary Economic Issues (NCVEI).
      Partnerships with industry are also possible and should be strongly considered.

PMID- 14648505
TI  - The proposed use of "participatory video" techniques in undergraduate veterinary
      education.

PMID- 14648506
TI  - Veterinarians in population health and public practice: meeting critical national
      needs.

PMID- 14648518
TI  - Futile care and the neonate.
AB  - The concept of futile care is controversial and difficult to define. Efforts to
      prolong life, once considered an outcome of healing, may now be viewed by some as
      harmful acts of prolonging suffering. This article reviews a number of cases
      representing this challenging ethical dilemma, such as Baby K and MacDonald v.
      Milleville. The Baby Doe regulations, the Emergency Medical Treatment and Labor
      Act (EMTALA), and the Born-Alive Protection Act of 2001, also are discussed to
      provide an improved understanding of the legal framework that impacts ethical
      decision making. Nurses at the bedside must be equipped with the ethical
      knowledge and communication skills necessary to care for patients and families
      facing the ethical dilemma of futile care. An increased focus on neonatal
      palliative care is suggested to provide infants, families, and staff with the
      necessary tools to work through this painful process.

PMID- 14648519
TI  - Case report of a pressure ulcer in an infant receiving extracorporeal life
      support: the use of a novel mattress surface for pressure reduction.
AB  - This case report describes a 4350-gram male infant of 38 weeks gestation who was
      placed on extracorporeal life support. On day 4 of life, a large bilateral
      ecchymotic area involving the scapula and extending to the mid sacral-lumbar
      thoracic area was noted, placing the infant at significant risk for pressure
      ulcer formation. The infant's initial presentation, evaluation, treatment, and
      response to therapy are discussed. A review of the anatomy and physiology of
      neonatal skin and the etiology of pressure ulcers is described. The incidence and
      staging of pressure ulcers is outlined, and high-risk infants and skin zones are
      identified. Skin care challenges in the patient on extracorporeal life support
      (ECLS) are outlined, and strategies to assess and treat affected areas are
      offered. The use of a novel mattress surface for global pressure reduction in the
      infant undergoing ECLS therapy is discussed.

PMID- 14648520
TI  - Assessment of the infant with a peripheral intravenous device.
AB  - Inserting, monitoring, and maintaining peripheral venous access is an integral
      component of neonatal nursing care. Although complications associated with
      peripheral vascular devices are typically minor, some infants may experience life
      threatening sequelae or serious and prolonged alterations in function. This
      article provides a review of the relevant anatomy and physiology of the
      peripheral venous system, techniques for maintaining catheter security, and
      guidelines for conducting a systematic physical assessment. The most commonly
      occurring complications, such as infiltration, phlebitis, and occlusion, are
      described. The etiology of the complications, signs and symptoms, and key
      evidence-based prevention strategies are outlined.

PMID- 14648521
TI  - The influence of gestational age on the efficacy and short-term safety of sucrose
      for procedural pain relief.
AB  - BACKGROUND: Physiologic and behavioral responses to procedural pain are
      influenced by gestational age (GA). Compared with term neonates, hospitalized
      preterm neonates are subjected to more painful procedures aimed at improving
      their clinical outcome. Although several trials to determine the efficacy of
      sucrose for managing procedural pain have been conducted, none have examined the
      influence of GA. OBJECTIVES: To examine the influence of GA on the efficacy and
      short-term safety of oral sucrose for relieving procedural pain associated with
      heel lances. To explore GA differences in behavioral and physiologic indicators
      of pain. METHODS: As part of a larger randomized controlled trial (RCT) to
      examine the efficacy and safety of sucrose during heel lance, 190 neonates were
      stratified by GA: (a) 27 to 316/7 weeks (group 1; n = 63), (b) 32 to 356/7 weeks
      (group 2; n = 63), and (c) >36 weeks (group 3; n = 64). They were then randomized
      to receive (a) oral sucrose and non-nutritive sucking (NNS), (b) sucrose alone,
      or (c) sterile water and NNS (control) for a heel lance. The influence of GA was
      determined by examining the short-term safety, as defined by the number of
      associated adverse events (choking, coughing or vomiting, sustained tachycardia,
      sustained tachypnea or dyspnea, or sustained oxygen desaturation). The efficacy
      was measured by changes in a validated pain measure, scored during each phase of
      the intervention and analyzed according to GA groups. RESULTS: Significant
      differences in pain response existed in each GA group, with the lowest mean pain
      scores in the sucrose and NNS group. Significant GA differences in behavioral and
      physiologic responses were found, with the most mature neonates demonstrating the
      greatest magnitude of pain response. The greatest number of short-term adverse
      effects to treatment occurred in the lowest GA group. CONCLUSIONS: In a secondary
      analysis of a larger RCT, sucrose and NNS was the most efficacious intervention
      for single heel lances in each of 3 GA groups. However, infants of lower GA
      experienced more adverse events. Research on the efficacy and safety of repeated
      doses of oral sucrose, tested in infants from a wide range of GA, is required.

PMID- 14648522
TI  - Providing culturally sensitive care to the childbearing Islamic family: Part II.
AB  - Culturally sensitive care requires a unique combination of empathy, curiosity,
      and a profound respect for others. This article provides insight into the Islamic
      family structure and the traditional male and female roles that health care
      providers may encounter. Best practice considerations focused on communication
      with and care of the family during hospitalization, and strategies to support
      breastfeeding, dietary, and medication requirements are provided. Neonatal end-of
      life decision making and death rituals are also discussed in context with
      commonly held religious beliefs and practices of this population.

PMID- 14648527
TI  - Complications associated with cannula insertion techniques used for laparoscopy
      in standing horses.
AB  - OBJECTIVE: To report our experience and complications associated with different
      cannula insertion techniques for laparoscopy in standing horses. STUDY DESIGN:
      Retrospective study. SAMPLE POPULATION: Forty horses that had laparoscopy for
      diagnostic or surgical purposes. METHODS: After a physical examination, including
      rectal palpation, standing laparoscopy was performed in 40 sedated horses. Local
      anesthetic was injected at each site of cannula insertion in the left flank.
      Horses were divided into 5 groups: Pneumoperitoneum was induced before cannula
      insertion using a Verres needle (group 1, n = 3) or a 12-g catheter (group 2, n =
      14); the cannula was inserted before inducing a pneumoperitoneum (group 3, n =
      9); the cannula was inserted under visual control, using an operating laparoscope
      (group 4, n = 2) or a Visiport Optical Trocar (group 5, n = 12). Horses were
      observed for 7 days. RESULTS: Problems with insufflation or cannula insertion
      occurred in 12 horses: 6 had peritoneal detachment, 4 had a splenic puncture, and
      2 had descending colon puncture. Eleven of these complications occurred in groups
      1 to 3 and only 1 in groups 4 and 5. CONCLUSIONS: The Visiport optical device
      allows controlled insertion of the initial trocar, and thus avoided potential
      problems associated with "blind" cannula insertion techniques and was used
      effectively in horses that had feed withheld for 12 hours. This technique enables
      direct insertion of a cannula directly into the right flank. CLINICAL RELEVANCE:
      Complications associated with initial cannula insertion in the paralumbar fossa,
      for laparoscopy, in standing horses can be minimized with the use of an optical
      cannula.

PMID- 14648528
TI  - A mechanical comparison of veterinary linear external fixation systems.
AB  - OBJECTIVE: To compare the fixation rigidity of recently developed external
      fixation systems (EFSs) to that of the traditional Kirschner-Ehmer (KE) system.
      STUDY DESIGN: In vitro biomechanical study. SAMPLE POPULATION: Five different
      EFSs (KE, Secur-U, small SK carbon fiber, small SK titanium, large SK carbon
      fiber) were assembled into 7 frame geometries to stabilize Delrin plastic rods
      with a 1-cm gap. METHODS: External skeletal fixation (ESF) constructs were tested
      in axial compression, torsion, medial-lateral bending, and cranial-caudal
      bending. Testing was conducted within the elastic range of each fixator. Mean
      stiffness in each mode was determined from the slope of the linear portion of the
      load-deformation curve. Comparison of stiffness values of each EFS within each
      loading mode and frame type was performed with 1-way analysis of variance (P
      <.05). RESULTS: Mean stiffness values were significantly higher for the large SK
      EFS in all frame types compared with KE but were equal in torsional stiffness in
      the double-bar type 1a frame. The small SK EFS with titanium connecting bar had
      greater stiffness than the KE in all modes for frame types Ia, Ia-accessory bar,
      and II-modified. No overall difference was detected between the KE EFS and the
      small SK with carbon fiber rod. The stiffness of the Secur-U type Ia frame with
      augmentation plate was significantly greater than the KE type Ia with accessory
      bar. CONCLUSIONS: The newer external fixation systems evaluated in this study
      provided fixation rigidity equal to or greater than that of the KE system.
      CLINICAL RELEVANCE: EFSs with increased frame rigidity should permit the use of
      less complex frame designs while providing fracture stability.

PMID- 14648529
TI  - The effect of topical tripeptide-copper complex on healing of ischemic open
      wounds.
AB  - OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine
      tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation, Redmond, WA)
      on healing in ischemic open wounds. STUDY DESIGN: Experimental study. SAMPLE
      POPULATION: Twenty-four adult male Sprague-Dawley rats. METHODS: Rats were
      divided into 3 groups: topical TCC, topical TCC vehicle (hydroxypropyl
      methylcellulose), and no treatment (control). Six-mm-diameter, full-thickness
      wounds were created within an ischemic bipedicle skin flap on the dorsum of each
      rat. Each day, for 13 days, wound margins were traced, and the TCC and TCC
      vehicle groups were treated topically. Tracings were scanned, and wound perimeter
      and area were calculated. On days 6, 10, and 13, selected wounds were biopsied
      and analyzed for tumor necrosis factor alpha (TNF-alpha) and matrix
      metalloproteinases (MMP) 2 and 9. RESULTS: A significant decrease in wound area
      was seen in the TCC group, but not the vehicle group, when compared with the
      control group on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with
      TCC vehicle on days 3 and 9. On day 13, initial wound area had decreased by 64.5%
      in the TCC group, 45.6% in the vehicle group, and 28.2% in the control group. On
      days 6, 10, and 13, TCC-treated wounds contained significantly lower
      concentrations of TNF-alpha and MMP-2 and MMP-9 than control wounds. CONCLUSION:
      Topical TCC resulted in accelerated wound healing in ischemic open wounds.
      CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of ischemic
      open wounds in rats and may have an application for the treatment of chronic
      wounds in other species. Clinical evaluation of topical TCC is warranted.

PMID- 14648530
TI  - Thoracoscopic treatment of bullous emphysema in 3 dogs.
AB  - OBJECTIVE: To report thorascopic partial lobectomy for treatment of bullous
      emphysema in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Three dogs
      with spontaneous pneumothorax. METHODS: Thoracoscopy without pulmonary exclusion
      was used to identify bulla. The thorascope was introduced into the thorax lateral
      to the xyphoid process, and instrument portals were made at different levels
      along the thoracic wall between the third and tenth intercostal spaces. The
      thorascope was passed through the mediastinum to view the opposite pleural
      cavity. After identification of bullae, the affected lung was excised using an
      endoscopic stapler, and the incision line was checked for air leakage. Thoracic
      drains were used for air aspiration for 2 days after surgery. RESULTS: Bullae
      were confirmed histologically as emphysematous lesions. Lung inflation did not
      interfere with identification of bullae or with surgery. All dogs had full
      recovery without recurrence for 18 to 29 months after surgery. CONCLUSIONS:
      Identification and ablation of bulla can be performed thoracoscopically without
      pulmonary exclusion in dogs. CLINICAL RELEVANCE: Thoracoscopy offers several
      advantages compared with thoracotomy for treatment and diagnosis of idiopathic
      pneumothorax, including ease of identification of bullae and reduced
      postoperative pain and morbidity.

PMID- 14648531
TI  - Laryngoplasty with ventriculectomy or ventriculocordectomy in 104 draft horses
      (1992-2000).
AB  - OBJECTIVE: To evaluate efficacy and safety of laryngoplasty with vetriculectomy
      (VE) or ventriculocordectomy (VCE) for treatment of laryngeal hemiplegia (LH) in
      draft horses. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: One hundred
      four draft horses used for competitive hitch competitions. METHODS: Medical
      records and postoperative endoscopy for competitive hitch draft horses diagnosed
      with left LH and treated with laryngoplasty and VE or VCE between January 1992
      and December 2000 were reviewed. Follow-up information was obtained from
      telephone interviews with owners and trainers, and performance scores of 1 to 3
      were assigned in which 1 was defined as a horse that was unable to perform
      (abnormal respiratory noise with or without exercise intolerance), 2 was able to
      perform but not for its intended use (exercise tolerant but abnormal respiratory
      noise), and 3 was performing as expected for its intended use (exercise tolerant,
      no abnormal respiratory noise). RESULTS: One hundred four horses that had 111
      laryngoplasty procedures were included. All horses had preoperative performance
      scores of 1. Follow-up information was available for 79 horses. Improvement in
      postoperative performance (exercise tolerant, with or without abnormal
      respiratory noise) was reported in 92% of horses. Respiratory noise was
      eliminated in 72% (57 horses) of horses. Postoperative performance scores were
      the following: 3 in 57 (72%) horses, 2 in 16 (20%) horses, and 1 in 6 (8%)
      horses. There was no significant difference in postoperative performance based on
      preoperative grade of LH. There was a trend for horses with >/=70% of possible
      maximal abduction postoperatively to have a performance score of 3.
      Postanesthetic complications included prolonged recovery (4 horses, 4%) and
      myopathy or neuropathy (7 horses, 7%). One of these horses was killed because it
      did stand; triceps myopathy and encephalopathy were confirmed on necropsy.
      CONCLUSIONS: Laryngoplasty with VE or VCE is an effective and safe procedure for
      the treatment of LH in the draft horse. Repeat laryngoplasty can be performed
      successfully, with good performance outcome after laryngoplasty failure.
      Complications associated with general anesthesia and laryngoplasty in draft
      horses are higher than reported for light breed horses under similar conditions.
      CLINICAL RELEVANCE: For LH, laryngoplasty with VCE or VE under general anesthesia
      is recommended to eliminate abnormal respiratory noise and improve performance in
      most competitive hitch draft horses.

PMID- 14648532
TI  - Pasteurized tumoral autograft and adjuvant chemotherapy for the treatment of
      canine distal radial osteosarcoma: 13 cases.
AB  - OBJECTIVE: To report outcome in 13 dogs with distal radial osteosarcoma, without
      evidence of metastasis, treated by a combination of adjuvant chemotherapy and a
      pasteurized autograft limb-sparing procedure. STUDY DESIGN: Prospective clinical
      study. ANIMALS: Thirteen dogs with distal radial osteosarcoma. METHODS: Limb
      sparing procedure was performed using an autograft from the excised tumoral
      segment, pasteurized at 65 degrees C for 40 minutes. Adjuvant chemotherapy
      (cisplatin or cisplatin and doxorubicin) was administered in all dogs. RESULTS:
      Mean and median survival times were 531 and 324 days, respectively (range, 180 to
      1,868 days). Overall survival was 100% at 6 months, 50% at 12 months, 44% at 18
      months, and 22% at 24 months. Lung metastasis occurred in 5 (38%) dogs. Observed
      complications were local recurrence (2 dogs, 15%), allograft infection (4 dogs,
      31%), and implant failure (3 dogs, 23%). Limb function was good in 12 dogs (92%)
      and fair in 1 dog. CONCLUSIONS: Pasteurized bone autograft derived from the
      tumoral bone segment was an effective alternative to cortical bone allograft for
      limb sparing in canine distal radial osteosarcoma, in terms of feasibility,
      pattern of healing, complications, and survival. CLINICAL RELEVANCE: Use of a
      pasteurized bone autograft eliminates the need for a canine bone allograft bank
      and has the added advantage of good fit to the recipient site.

PMID- 14648533
TI  - Short-term outcome after total elbow arthroplasty in dogs with severe, naturally
      occurring osteoarthritis.
AB  - OBJECTIVE: To evaluate limb function in client-owned dogs before and after total
      elbow arthroplasty (TEA) for severe, naturally occurring osteoarthritis (OA).
      STUDY DESIGN: Prospective clinical evaluation comparing limb function before and
      after surgery. ANIMALS: Twenty adult, large breed dogs with elbow OA. METHODS:
      Physical, radiographic, and force platform gait examinations were performed on
      all dogs before surgery. TEA was performed, and examinations were repeated at 3,
      6, and 12 months after surgery. Pre- and postoperative findings were compared.
      RESULTS: TEA led to a satisfactory outcome in 16 dogs. In dogs with a
      satisfactory outcome, function in the operated limb increased over time, with
      mean peak vertical force (PVF) and vertical impulse (VI) 1 year after surgery
      being nearly twice the presurgical value. Serious complications encountered
      included infection (n = 2), luxation (n = 1), and fracture of the humeral condyle
      (n = 1). CONCLUSIONS: Although TEA, as presented, has significant limitations, it
      can be successfully performed in dogs with naturally occurring elbow OA.
      Improvements in technique and implant design should lead to improved prognosis.
      CLINICAL RELEVANCE: Based on 1-year data, TEA can be successfully performed in
      dogs and should be considered as a treatment alternative for adult dogs with
      lameness from severe OA of the elbow joint.

PMID- 14648534
TI  - Life-threatening hemorrhage from enterotomies and anastomoses in 7 horses.
AB  - OBJECTIVE: To report our experience with horses that presumptively had severe
      intraluminal hemorrhage from enterotomy or anastomosis. STUDY DESIGN: Clinical
      study. ANIMALS: Six adult horses and 1 adult donkey. METHODS: A retrospective
      study was conducted at the University of Illinois (April 1994 to December 2001)
      to determine the clinical course and outcome of horses with melena and/or anemia
      and evidence of life-threatening hemorrhage from intestinal incisions. Medical
      records of all horses that had colic surgery were reviewed to determine the
      proportion of horses with this complication. In addition, horses that fit the
      same criteria identified in 3 other veterinary clinics were included. RESULTS:
      Three horses (1.3%) of those that had enterotomy or anastomosis at the University
      of Illinois and 4 horses from other clinics had complications presumptively
      related to severe hemorrhage from these intestinal procedures. Melena became
      evident within 72 hours of surgery and lasted 12 to 96 hours. Six horses had an
      acute and severe drop in packed cell volume (PCV), increased heart rates, and
      other signs of acute hemorrhage, and 1 horse had signs of colic postoperatively.
      Horses were administered intravenous formalin (3 horses) and whole blood
      transfusions (4 horses). Repeat celiotomy was performed on 2 horses. In 1 of
      these horses, a bleeding artery was ligated in the edge of the original
      enterotomy, and, in the other, a 25-cm-diameter intraluminal blood clot was found
      occluding the pelvic flexure. A horse that had jejunocolostomy for cecal
      impaction was not treated for hemorrhagic shock but was euthanatized and
      necropsied. Necropsy revealed blood-filled bowel from the jejunocolostomy to the
      anus. One of the remaining 6 horses died of enterocolitis and 5 survived to
      discharge. CONCLUSIONS: Hemorrhage from incisional edges, particularly in the
      large intestine, should be considered a rare but possibly fatal complication of
      enterotomy or anastomosis in horses. CLINICAL RELEVANCE: To prevent fatal
      hemorrhage from incisional edges during enterotomy or anastomosis, large vessels
      should be ligated at the original surgery, and hemostatic effects of different
      closure techniques should be considered. No intraoperative or postoperative
      findings were useful to predict this complication, and response to supportive
      medical therapy was favorable.

PMID- 14648535
TI  - Bone gentamicin concentration after intra-articular injection or regional
      intravenous perfusion in the horse.
AB  - OBJECTIVE: To compare intra-articular (IA) and bone gentamicin concentrations
      achieved after intra-articular administration or regional intravenous perfusion
      (RIP). STUDY DESIGN: Experimental study. ANIMALS: Twelve healthy adult horses.
      METHODS: Horses were assigned to 2 treatment groups (n = 6/group): Group 1, 1 g
      gentamicin administered simultaneously in both left and right metacarpophalangeal
      joints and group 2, 1 g gentamicin administered simultaneously in both left and
      right lateral palmar veins. Serum, synovial fluid, and bone biopsy specimens were
      collected. Gentamicin concentrations were determined by fluorescence polarization
      immunoassay. Bone, synovial fluid, and serum gentamicin concentrations were
      compared over time and between groups using 2-way ANOVA. Significance of all
      tests were evaluated at P <.05. RESULTS: IA metacarpophalangeal joint
      administration resulted in higher concentration of gentamicin in synovial fluid
      than RIP administration. Synovial fluid concentration remained above minimum
      inhibitory concentration (MIC) for common pathogens for over 24 hours with IA and
      RIP administration. Bone gentamicin concentration remained above MIC for 8 hours
      with both methods; there was no significant difference in gentamicin
      concentration in bone with either method. Neither IA nor RIP administration had a
      significant effect on serum concentration of gentamicin. CONCLUSIONS: In normal
      horses, there is no difference in bone gentamicin concentration obtained with IA
      or RIP administration. CLINICAL RELEVANCE: Based on MIC for common equine
      pathogens, administration of gentamicin intra-articularly or by regional
      intravenous perfusion should be useful for treatment of osteomyelitis.

PMID- 14648536
TI  - Effect of fenoldopam on renal function after nephrotomy in normal dogs.
AB  - OBJECTIVE: To evaluate effects of fenoldopam on renal function in normal dogs
      subjected to bisection nephrotomy. In addition, effects of bisection nephrotomy
      on renal function in normal dogs were evaluated. STUDY DESIGN: Controlled,
      randomized, blinded experiment. SAMPLE POPULATION: Sixteen mixed-breed adult
      dogs. METHODS: Dogs were paired for sex, body weight, and approximate age and
      assigned to 1 of 2 groups: fenoldopam (F) or placebo (P). Baseline glomerular
      filtration rate (GFR) based on quantitative renal scintigraphy using (99m)Tc
      DTPA, blood urea nitrogen (BUN), serum creatinine (SCr), urinalysis, and urine
      culture were performed before surgery. Left nephrotomy was performed via median
      celiotomy. Group F dogs were administered intravenous (IV) fenoldopam (0.1
      microg/kg/min) for 90 minutes, whereas group P dogs were administered an
      equivalent volume of saline (0.9 % NaCl) solution for 90 minutes. Temperature,
      heart rate, respiration, direct arterial blood pressure, and urine volume were
      recorded during anesthesia. Renal function was assessed by measuring SCr, BUN,
      and GFR at 1, 21, and 42 days after surgery. RESULTS: There was no significant
      difference between groups in measured physiologic variables. No significant
      difference in GFR, BUN, or SCr between groups or between operated or control
      kidneys was detected. CONCLUSIONS: Bisection nephrotomy in normal dogs with renal
      arterial occlusion of 15 minutes and using a simple continuous capsular closure
      does not adversely affect renal function. CLINICAL RELEVANCE: Bisection
      nephrotomy, as described in this study, does not decrease renal function;
      perioperative administration of renoprotective agents is not necessary in normal
      dogs.

PMID- 14648537
TI  - Evaluation of a vessel-sealing device for small intestinal resection and
      anastomosis in normal horses.
AB  - OBJECTIVES: To compare arterial bursting pressure after vessel closure using a
      vessel-sealing device (LigaSure Atlas Laparoscopic Sealer/Divider Instrument;
      Valleylab, Boulder, CO), a ligate-and-divide stapling device (LDS), and 2-0
      polydioxanone suture. To evaluate the LigaSure Atlas as a method for ligation of
      the mesenteric vasculature during small intestinal resection in normal horses.
      STUDY DESIGN: Experimental study. ANIMALS: Part A: jejunal segments from 19
      horses. Part B: 6 horses, aged 1 to 18 years, weighing 330 to 509 kg. METHODS:
      Part A: Jejunal segments with mesenteric vessels were collected from 19 horses.
      After closure by 1 of 3 methods (LigaSure Atlas, LDS, 2-0 polydioxanone) arteries
      were cannulated, and bursting pressure was measured by incrementally increasing
      intraluminal pressure until failure. Part B: Six horses had jejunal resection and
      anastomosis using a vessel-sealing device (LigaSure Atlas) to provide hemostasis
      of the mesenteric vasculature. Horses were monitored clinically for 4 weeks.
      RESULTS: Part A: Mean +/- SEM bursting pressure after 2-0 polydioxanone ligation
      (1,014.50 +/- 279.05 mm Hg) was significantly greater than mean bursting pressure
      after LigaSure (554.25 +/- 228.79 mm Hg), which was significantly greater than
      the mean bursting pressure after LDS (373.25 +/- 183.69). Part B: No major
      operative or postoperative hemorrhage occurred after application of the LigaSure
      Atlas for sealing and transecting mesenteric vasculature during small intestinal
      resection in normal horses. CONCLUSIONS: The LigaSure Atlas appears to be a safe
      method for hemostasis of the mesenteric vasculature during small intestinal
      resection in normal horses. CLINICAL RELEVANCE: Benefits of the LigaSure Atlas
      vessel-sealing device include reduced time required to provide hemostasis,
      acceptable arterial bursting pressure, no remaining foreign material, and no risk
      for ligature slippage. In our experience, use of the LigaSure Atlas during small
      intestinal resection and anastomosis in horses is safe for ligation of vessels
      less than or equal to 7-mm diameter.

PMID- 14648538
TI  - An ex vivo mechanical evaluation of single versus double semitubular plate
      fixation of a transverse distal-third scapular osteotomy in the dog.
AB  - OBJECTIVE: To compare single versus double semitubular plate fixation for
      scapular body fractures. STUDY DESIGN: Ex vivo mechanical study. SAMPLE
      POPULATION: Eighteen paired cadaveric canine scapulae. METHODS: Transverse
      scapular body osteotomies were created in the distal third of 18 pairs of
      scapulae. One scapula of each pair was repaired with a single plate, whereas the
      contralateral scapula was repaired with 2 plates. Initial strength and stiffness
      of the constructs were measured in 10 pairs of scapulae. Eight pairs of scapulae
      underwent cyclic loading and then were subjected to failure testing. RESULTS:
      Double-plate fixation was significantly stronger (3,899 +/- 632 N) but not
      stiffer (614 +/- 130 N/mm) than the single-plate fixation (3,238 +/- 935 N and
      537 +/- 202 N/mm, respectively). Cyclic loading variables were not significantly
      different between the 2 methods of fixation. After cyclic loading, double-plate
      fixation was significantly stronger (2,916 +/- 618 N) than single-plate fixation
      (2,347 +/- 495 N). There was no significant difference (P =.11) in stiffness
      between double- versus single-plate fixations: 734 +/- 247 N/mm and 595 +/- 139
      N/mm, respectively. CONCLUSIONS: Double-plate fixation was generally stronger and
      stiffer than single-plate fixation. Because all constructs failed at loads that
      greatly exceeded those estimated to occur clinically, any difference between the
      2 methods of fixation probably is not clinically relevant. CLINICAL RELEVANCE:
      Single-plate fixation may be of sufficient strength for fixation of scapular body
      fractures.

PMID- 14648539
TI  - Biomechanical investigation of the association between suspensory ligament injury
      and lateral condylar fracture in thoroughbred racehorses.
AB  - Objective-To determine whether partial transection of the medial branch of the
      suspensory ligament (MBSL) alters equine third metacarpal bone (MC3) condylar
      surface strains and forelimb, distal joint angles in a manner consistent with
      promotion of lateral condylar fracture. Study Design-In vitro biomechanical
      experiment. Sample Population-Right forelimbs from 7 Thoroughbred horse cadavers.
      Methods-Lateral and medial MC3 condylar, dorsal and abaxial, bone surface strains
      and distal joint angles were measured both before and after partial transection
      of the MBSL during in vitro axial limb compression. Dorsal, principal bone
      strains and abaxial, uniaxial, and proximodistal strains were compared before and
      after MBSL partial transection at 1,400-, 3,000-, and 5,600-N loads. Results-Bone
      strains increased in all locations with increasing axial load. All lateral
      condylar bone strains were significantly higher, and abaxial surface medial
      condylar bone strain was significantly lower, after partial transection of the
      MBSL. Respective distal joints became more flexed or extended as axial load
      increased but were not significantly different after partial transection of the
      MBSL. Conclusions-Partial transection of the MBSL increases in vitro MC3 lateral
      condylar bone surface strains. Clinical Relevance-Loss of integrity of the medial
      branch of the suspensory ligament could increase the risk for lateral condylar
      fracture in Thoroughbred horses by amplifying bone strain in the lateral condyle.

PMID- 14648541
TI  - Transplantation of glial-restricted precursor cells into the adult spinal cord:
      survival, glial-specific differentiation, and preferential migration in white
      matter.
AB  - Glial-restricted precursor (GRP) cells are among a number of candidate cells for
      transplantation repair of CNS injury. The isolation and characterization of these
      cells in vitro have been described previously, but their in vivo properties are
      not well understood. We examined the fate and migration of grafted fetal GRP
      cells harvested from alkaline phosphatase-expressing transgenic rats into intact
      and injured spinal cord. Transplanted GRP cells survived for at least 6 weeks and
      differentiated along astrocytic and oligodendrocytic but not neuronal lineages.
      Cells grafted into the intact spinal cord exhibited robust migration along
      longitudinal white matter tracts and by 6 weeks migrated more than 15 mm. In
      contrast, migration of GRP cells in the gray matter was very limited. We then
      examined the phenotypic properties of proliferating endogenous precursors in
      response to injury by BrdU labeling. The predominant proliferating population
      seen after injury consisted of GRP-like cells with Nkx2.2/olig2 phenotype.
      Incorporation of BrdU by endogenous cells suggests that the environment provides
      proliferation signals and is permissive to glial precursor survival. To test if
      exogenous GRP cells would respond similarly, we transplanted GRP cells into a
      lateral funiculus injury. GRP cells survived and differentiated along glial
      lineages and migrated along white matter tracts in the injured spinal cord.
      Directed homing toward the lesion was not seen and there was no significant bias
      in differentiation between cells transplanted into injured and uninjured spinal
      cord. GRP cell transplants may therefore provide a cellular transplant that can
      respond to appropriate endogenous cues to produce therapeutic molecules and new
      glial cells after injury.

PMID- 14648542
TI  - Characterization of lysophosphatidic acid and sphingosine-1-phosphate-mediated
      signal transduction in rat cortical oligodendrocytes.
AB  - Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been proposed
      to play a key role in oligodendrocyte maturation and myelinogenesis. In this
      study, we examined lysophospholipid receptor gene expression in differentiated
      rat oligodendrocyte cultures and signaling downstream of lysophospholipid
      receptor activation by LPA and S1P. Differentiated oligodendrocytes express mRNAs
      encoding lysophospholipid receptors with the relative abundance of
      lpa1>s1p5>s1p1=s1p2=lpa3>s1p3. LPA and S1P transiently increased phosphorylation
      of extracellular signal-regulated kinase (ERK) with EC50 values of 956 and 168
      nM, respectively. LPA- and S1P-induced ERK phosphorylation was dependent on the
      activation of mitogen-activated protein kinase (MAPK), phospholipase C (PLC), and
      protein kinase C (PKC), but was insensitive to pertussis toxin (PTX). LPA
      increased intracellular calcium levels in oligodendrocytes and these increases
      were partially blocked by a PLC inhibitor but not by PTX. In contrast, S1P was
      not found to induce measurable changes of intracellular calcium. These results
      taken together suggest that lysophospholipid receptor activation involves
      receptor coupling to heterotrimeric Gq subunits with consequent activation of
      PLC, PKC, and MAPK pathways leading to ERK phosphorylation.

PMID- 14648543
TI  - Hydrogen peroxide increases gap junctional communication and induces astrocyte
      toxicity: regulation by brain macrophages.
AB  - Cultured astrocytes are highly coupled by gap junction channels mainly
      constituted by connexin 43. We have previously shown that gap junctional
      communication (GJC) represents a functional property of astrocytes that is a
      target for their interaction with other brain cell types, including neurons and
      brain macrophages. In pathological situations, neurons as well as brain
      macrophages produce superoxide ions leading to the formation of hydrogen peroxide
      (H2O2) that can be cytotoxic. We report here that 10-min exposure to 100 microM
      H2O2 increases GJC in astrocytes. Moreover, 30-min exposure to 100 microM H2O2
      induces, 24 h later, an astrocyte cell death by both apoptosis and necrosis. This
      H2O2-induced astrocyte cell death is not affected when gap junctions are
      inhibited by several uncoupling agents, including 18alpha-glycyrrhetinic acid,
      halothane, heptanol, and endothelin-1, indicating that the proportion of cell
      death is not related to the level of GJC. The effect of H2O2 on gap junction
      channels does not result from the production of free radicals but is rather
      linked to modification of the redox equilibrium in astrocytes. Indeed, an
      oxidative agent reproduces the H2O2-evoked response while reducing agents prevent
      the effect of H2O2. Finally, when astrocytes are cocultured with brain
      macrophages, the effects of H2O2 on both GJC and toxicity are not observed,
      revealing a new protective role of brain macrophages during oxidative stress.

PMID- 14648544
TI  - The 4C5 antigen is associated with Schwann cell migration during development and
      regeneration of the rat peripheral nervous system.
AB  - The monoclonal antibody 4C5 recognizes a cell surface antigen of the developing
      central nervous system (CNS) and peripheral nervous system (PNS). In vitro
      antibody perturbation experiments have shown that the 4C5 antigen is involved in
      horizontal and vertical migration processes of granule cells during development
      of the rodent cerebellum. Moreover, results concerning the cellular localization
      and temporal expression of the 4C5 antigen during development and after injury of
      the rat sciatic nerve suggested that it may participate in Schwann cell
      migrations that occur during the above processes. To test this possibility, we
      examined the effects of our function-blocking antibody on Schwann cell migration
      in three in vitro bioassays: in tissue cultures from developing sciatic nerve, in
      dorsal root ganglion cultures on cryostat sections of normal or denervated adult
      sciatic nerve, and in pure Schwann cell cultures. The results showed that the
      presence of monoclonal antibody 4C5 in all the above culture systems strongly
      inhibited Schwann cell migration, indicating that the 4C5 antigen participates in
      migration processes that take place during development and regeneration of the
      peripheral nervous system. Moreover, staining of migrating Schwann cells in the
      presence of monoclonal antibody 4C5 with rhodamine-phalloidin showed that 4C5
      antigen activity is associated with actin cytoskeletal organization of these
      cells, and more specifically with lamellipodia formation.

PMID- 14648545
TI  - Antioxidants are necessary for myelination of dorsal root ganglion neurons, in
      vitro.
AB  - We have demonstrated that myelination of dorsal root ganglion (DRG) axons occurs
      in a fully defined, serum-free medium (B27). This implies that there may be
      components in B27 medium that support myelination. To determine which of the
      components in B27 were essential for myelination, we systematically removed
      components from B27 until myelination was lost. We added these components to a
      fully defined minimal medium (N2) that supports neuron survival but not
      myelination. When antioxidants were removed from B27, myelination was lost.
      However, the individual antioxidants did not induce myelination when added to N2
      medium. Addition of ascorbic acid along with the B27 antioxidants was sufficient
      to induce myelination in N2 medium, which was enhanced by retinyl acetate.
      Removal of vitamin E from B27 caused a partial loss of myelination, and addition
      of vitamin E to N2 medium containing ascorbic acid induced partial myelination.
      Addition of serum to the B27 myelinating medium inhibited myelination completely.
      These results indicate that antioxidants are important for myelination, in vitro.
      Vitamin E may play an important role. Use of a serum-free medium may be
      beneficial for in vitro myelination studies because serum has unknown inhibitory
      effects.

PMID- 14648546
TI  - Selective staining by vital dyes of Muller glial cells in retinal wholemounts.
AB  - Muller glial cells within the retina may respond to different signaling molecules
      with an elevation of their intracellular free calcium. To prove the localization
      of the recorded calcium responses in Muller cells within acutely isolated retinal
      wholemounts, retinal pieces from adult animals and humans were exposed to
      different vital dyes just after the calcium imaging records were finished. The
      dyes, Mitotracker Orange, Mitotracker Green, Celltracker Orange, Celltracker
      Green, and monochlorobimane, are all selectively taken up by Muller glial cells,
      while neuronal cells remain largely devoid of the dyes. By using this method, it
      can be demonstrated that the free calcium alterations within the wholemounts
      indeed occur within Muller cells. Moreover, the cross-sectional areas of (dye
      filled) Muller glial cell bodies, as well as of (dye-free) neuronal cell bodies,
      can be measured in retinal wholemounts, and the spatial densities of both types
      of cells can be determined. The vital dye loading of Muller cells may facilitate
      investigations of stimulus-induced alterations of retinal glial cell physiology
      and morphology.

PMID- 14648547
TI  - Olig genes are expressed in a heterogeneous population of precursor cells in the
      developing spinal cord.
AB  - Recent results from multiple laboratories have identified Olig genes as important
      in regulating glial differentiation. Here we show that Olig2 expression at early
      stages of development (prior to E16.5) identifies a domain in the developing
      spinal cord, which contains a heterogeneous population of progenitors that
      includes stem cells and glial progenitors. We show that Nkx2.2 and Olig2, which
      are present initially in nonoverlapping domains, are coexpressed at later stages,
      likely due to a second wave of Olig expression. We find that Olig1, like Olig2,
      is present in cells that coexpress astrocytic and radial glial markers and that
      Olig1/2 double knockouts lead to a loss of oligodendrocytes with preservation of
      NG2 expression. These results coupled with previously published data indicate
      that Olig1/2 and Nkx2.2, while clearly important in regulating early progenitor
      cell differentiation, do not unambiguously demonstrate the existence of an
      oligodendrocyte-neuron precursor or negate the existing retroviral lineage and
      clonal analysis data that suggest the existence of other types of precursors such
      as oligodendrocyte-astrocyte precursors or neuronal precursors.

PMID- 14648548
TI  - Progressive telomere shortening occurs in cultured rat microglia, but not
      astrocytes.
AB  - Normal somatic cells have a finite replicative capacity. With each cell division,
      telomeres shorten progressively until they reach a critical length, at which
      point the cells enter replicative senescence. Some cells maintain their telomeres
      by the action of the telomerase enzyme. Glia, particularly microglia, are the
      only adult cell types in the central nervous system (CNS) that exhibit a
      significant mitotic potential, and are thus susceptible to telomere shortening.
      In this study, we show that telomere shortening accompanied by low to moderate
      telomerase activity, and ultimately senescence, occurs in rat microglia in vitro.
      When microglia are stimulated to divide with the mitogen granulocyte macrophage
      colony stimulating factor (GM-CSF), longer telomeres are allowed to shorten,
      while shorter telomeres are lengthened. Telomerase activity is nearly 3-fold
      higher in GM-CSF-stimulated microglia initially, relative to unstimulated
      controls, and then declines to levels below those seen in controls before
      increasing again. Telomere attrition is also more rapid when microglia are grown
      in culture dishes of increasing size. Fluorescence in situ hybridization (FISH)
      analysis indicates that a nearly 3-fold variation in both inter- and intra
      chromosomal telomere length exists in microglia. In contrast to microglia,
      cultured astrocytes exhibit a cyclical pattern of telomere lengthening and
      shortening over time, corresponding to a similar cycle of higher and lower
      telomerase activity. When astrocytes are passaged, mean telomere length increases
      initially from passage 1-2, remaining constant until passage 5, while the
      shortest telomeres are continually lengthened. In conclusion, the telomere
      shortening evident in microglia is accompanied by their progression to senescence
      by 32 days in vitro. In contrast, astrocytes, perhaps due to greater telomerase
      activity, have longer life spans and may be passaged repeatedly before entering
      senescence. Our findings provide an impetus to investigate the possibility that
      microglial telomere shortening may occur in vivo.

PMID- 14648549
TI  - Activation of p38 mitogen-activated protein kinase in spinal hyperactive
      microglia contributes to pain hypersensitivity following peripheral nerve injury.
AB  - Neuropathic pain is an expression of pathological operation of the nervous
      system, which commonly results from nerve injury and is characterized by pain
      hypersensitivity to innocuous stimuli, a phenomenon known as tactile allodynia.
      The mechanisms by which nerve injury creates tactile allodynia have remained
      largely unknown. We report that the development of tactile allodynia following
      nerve injury requires activation of p38 mitogen-activated protein kinase
      (p38MAPK), a member of the MAPK family, in spinal microglia. We found that
      immunofluorescence and protein levels of the dually phosphorylated active form of
      p38MAPK (phospho-p38MAPK) were increased in the dorsal horn ipsilateral to spinal
      nerve injury. Interestingly, the phospho-p38MAPK immunofluorescence in the dorsal
      horn was found exclusively in microglia, but not in neurons or astrocytes. The
      level of phospho-p38MAPK immunofluorescence in individual microglial cells was
      much higher in the hyperactive phenotype in the ipsilateral dorsal horn than the
      resting one in the contralateral side. Intrathecal administration of the p38MAPK
      inhibitor, 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H
      imidazole (SB203580), suppresses development of the nerve injury-induced tactile
      allodynia. Taken together, our results demonstrate that nerve injury-induced pain
      hypersensitivity depends on activation of the p38MAPK signaling pathway in
      hyperactive microglia in the dorsal horn following peripheral nerve injury.

PMID- 14648550
TI  - Microglia, a potential source of neurons, astrocytes, and oligodendrocytes.
AB  - Microglia are considered the only cell population of mesodermal origin in the
      brain, although their role is not fully understood. The present study
      demonstrated that rat primary microglial cells expressed nestin, A2B5, and O4
      antigens, which are markers for oligodendrocyte precursor cells. Based on these
      findings, we investigated whether microglial cells generated neurons or
      macroglial cells. Purified microglial cells were cultured in the presence of 10%
      fetal bovine serum for 3 days, followed by culture in the presence of 70% serum
      for 2 days. During the two-step culture, microglial cells became highly
      proliferative and strongly expressed inhibitor of DNA binding (Id) genes,
      indicative of dedifferentiation of the cells. The dedifferentiated cells also
      expressed transcription factors that promote differentiation into neurons or
      macroglial cells. When the dedifferentiated cells were transferred into serum
      free medium on poly-L-lysine-coated substrate, a substantial number of the cells
      rapidly turned into long process-bearing cells, which expressed microtubule
      associated protein 2, synapsin I, neurofilament proteins, glial fibrillary acidic
      protein, or galactocerebroside. When microglial cells were fluorescently labeled
      through acetylated low-density lipoprotein (LDL) receptors or by a phagocytosis
      dependent mechanism, fluorescence-bearing neurons, astrocytes, or
      oligodendrocytes were observed. Neurospheres, aggregates of neural stem cells,
      expressed Musashi 1 and epidermal growth factor receptor, but the microglia
      derived cells did not. These results suggest a novel role of microglia as
      multipotential stem cells to give rise to neurons, astrocytes, or
      oligodendrocytes.

PMID- 14648551
TI  - Satellite cell proliferation in murine sensory ganglia in response to
      scarification of the skin.
AB  - Satellite cells (SCs) ensheathe neuronal cell bodies of sensory ganglia and
      provide mechanical and metabolic support for neurons. In mice, grossly
      detrimental stimuli such as nerve crush or cut, or explant culture of ganglia
      induce proliferation of SCs. It is unknown whether SC proliferation occurs in
      response to the less severe trauma that might commonly occur in a physiological
      situation. Our aim was to determine the response of SCs to mild trauma, such as
      scratching the skin. SC proliferation, measured by bromodeoxyuridine (BrdU)
      uptake, and immune cells, measured by CD45 labelling, were quantified at various
      times during the 7 days after scarification or abrasion of flank skin. We show
      that minimal skin trauma, such as scarification or light abrasion, triggers
      proliferation of SCs. Sections of control mice nervous tissue show <10 BrdU+
      cells/ganglionic profile. In contrast, sections of traumatised mice show >50
      BrdU+ cells/ganglionic profile, even after simply scratching the skin. The lack
      of CD45+ cells shows that the proliferating cells are not immune cells. We
      suggest that SCs in mice are a labile cell population able to proliferate rapidly
      in response to minimal nerve trauma. This finding has implications for the role
      of SCs in nervous system repair.

PMID- 14648552
TI  - The centrosome: The centriole-PCM coalition.

PMID- 14648554
TI  - Actin-binding proteins required for reliable chromosome segregation in mitosis.
AB  - While studying mitosis in Dictyostelium mutants with deficiencies in actin
      binding proteins, we found that two of these proteins, cortexillin and Aip1, are
      required for the precise segregation of chromosomes. Atypical spindles and nuclei
      with varying DNA content indicate that mutants lacking cortexillin or Aip1 are
      genetically unstable. These aberrations are caused by the detachment and
      irregular reattachment of centrosomes to the nuclear surface. Live imaging showed
      how coalescing mitotic complexes give rise to a multipolar spindle, and how
      excess centrosomes can be eliminated by mitotic cleavage between anucleate and
      nucleated portions of a cell. We hypothesize that mutations in regulatory
      proteins of the actin network might be one cause of genetic instability of
      malignant tumor cells.

PMID- 14648553
TI  - The radial spokes and central apparatus: mechano-chemical transducers that
      regulate flagellar motility.

PMID- 14648555
TI  - Higher plant cortical microtubule array analyzed in vitro in the presence of the
      cell wall.
AB  - Plant morphogenesis depends on an array of microtubules in the cell cortex, the
      cortical array. Although the cortical array is known to be essential for
      morphogenesis, it is not known how the array becomes organized or how it
      functions mechanistically. Here, we report the development of an in vitro model
      that provides good access to the cortical array while preserving the array's
      organization and, importantly, its association with the cell wall. Primary roots
      of maize (Zea mays) are sectioned, without fixation, in a drop of buffer and then
      incubated as desired before eventual fixation. Sectioning removes cytoplasm
      except for a residuum comprising cortical microtubules, vesicles, and fragments
      of plasma membrane underlying the microtubules. The majority of the cortical
      microtubules remain in the cut-open cells for more than 1 h, fully accessible to
      the incubation solution. The growth zone or more mature tissue can be sectioned,
      providing access to cortical arrays that are oriented either transversely or
      obliquely to the long axis of the root. Using this assay, we report, first, that
      cortical microtubule stability is regulated by protein phosphorylation; second,
      that cortical microtubule stability is a function of orientation, with divergent
      microtubules within the array depolymerizing within minutes of sectioning; and
      third, that the polarity of microtubules in the cortical array is not uniform.
      These results suggest that the organization of the cortical array involves random
      nucleation followed by selective stabilization of microtubules formed at the
      appropriate orientation, and that the signal specifying alignment must treat
      orientations of +/- 180 degrees as equivalent.

PMID- 14648556
TI  - Aggregation and loss of cytokeratin filament networks inhibit golgi organization
      in liver-derived epithelial cell lines.
AB  - Intermediate filaments are one of the three major cytoskeletons. Some roles of
      intermediate filaments in cellular functions have emerged based on various
      diseases associated with mutations of cytokeratins. However, the precise
      functions of intermediate filament are still unclear. To resolve this, we
      manipulated intermediate filaments of cultured cells by expressing a mutant
      cytokeratin. Arginine 89 of cytokeratin18 plays an important role in intermediate
      filament assembly. The expression of green fluorescent protein-tagged
      cytokeratin18 arg89cys induced aggregations and loss of the intermediate filament
      network composed of cytokeratins in liver-derived epithelial cells, Huh7 and
      OUMS29, but only induced the formation of cytokeratin aggregates and did not
      affect the intermediate filament network of endogenous vimentin in HEK293. The
      expression of this mutant affected the distribution of Golgi apparatus and the
      reassembly of Golgi apparatus after perturbations by nocodazole or brefeldin A in
      both Huh7 and OUMS29, but not in HEK293. Our data show that loss of the original
      intermediate filament network, but not the existence of cytokeratin aggregates,
      induces redistribution of the Golgi apparatus. The original intact intermediate
      filament network is necessary for the organization of Golgi apparatus.

PMID- 14648557
TI  - PLA2 and secondary metabolites of arachidonic acid control filopodial behavior in
      neuronal growth cones.
AB  - The neuronal growth cone provides the sensory and motor structure that guides
      neuronal processes to their target. The ability of a growth cone to navigate
      correctly depends on its filopodia, which sample the environment by continually
      extending and retracting as the growth cone advances. Several second messengers
      systems that are activated upon contact with extracellular cues have been
      reported to affect growth cone morphology by changing the length and number of
      filopodia. Because recent studies have suggested that guidance cues can signal
      via G-protein coupled receptors to regulate phospholipases, we here investigated
      whether phospholipase A2 (PLA2) may control filopodial dynamics and could thereby
      affect neuronal pathfinding. Employing identified Helisoma neurons in vitro, we
      demonstrate that inhibition of PLA2 with 2 microM BPB caused a 40.3% increase in
      average filopodial length, as well as a 37.3% reduction in the number of
      filopodia on a growth cone. The effect of PLA2 inhibition on filopodial length
      was mimicked by the inhibition of G-proteins with 500 ng/ml pertussis toxin and
      was partially blocked by the simultaneous activation of PLA2 with 50 nM melittin.
      We provide evidence that PLA2 acts via production of arachidonic acid (AA),
      because (1) the effect of inhibition of PLA2 could be counteracted by supplying
      AA exogenously, and (2) the inhibition of cyclooxygenase, which metabolizes AA
      into prostaglandins, also increased filopodial length. We conclude that
      filopodial contact with extracellular signals that alter the activity of PLA2 can
      control growth cone morphology and may affect neuronal pathfinding by regulating
      the sensory radius of navigating growth cones.

PMID- 14648558
TI  - High-resolution 1H NMR spectroscopy in a live mouse subjected to 1.5 Hz magic
      angle spinning.
AB  - It is demonstrated that the resolution of the (1)H NMR metabolite spectrum in a
      live mouse can be significantly enhanced by an ultraslow magic angle spinning of
      the animal combined with a modified phase-corrected magic angle turning (PHORMAT)
      pulse sequence. Proton NMR spectra were measured of the torso and the top part of
      the belly of a female BALBc mouse in a 2 T field while spinning the animal at a
      speed of 1.5 Hz. It was found that even in this relatively low field, with
      PHORMAT an isotropic spectrum is obtained with line widths that are a factor of
      4.6 smaller than those obtained in a stationary mouse. It is concluded that in
      vivo PHORMAT has the potential to significantly increase the utility of (1)H NMR
      spectroscopy for biochemical and biomedical animal research.

PMID- 14648559
TI  - Amide proton transfer (APT) contrast for imaging of brain tumors.
AB  - In this work we demonstrate that specific MR image contrast can be produced in
      the water signal that reflects endogenous cellular protein and peptide content in
      intracranial rat 9L gliosarcomas. Although the concentration of these mobile
      proteins and peptides is only in the millimolar range, a detection sensitivity of
      several percent on the water signal (molar concentration) was achieved. This was
      accomplished with detection sensitivity enhancement by selective radiofrequency
      (RF) labeling of the amide protons, and by utilizing the effective transfer of
      this label to water via hydrogen exchange. Brain tumors were also assessed by
      conventional T(1)-weighted, T(2)-weighted, and diffusion-weighted imaging.
      Whereas these commonly-used approaches yielded heterogeneous images, the new
      amide proton transfer (APT) technique showed a single well-defined region of
      hyperintensity that was assigned to brain tumor tissue.

PMID- 14648560
TI  - Out-and-in spiral spectroscopic imaging in rat brain at 7 T.
AB  - With standard spectroscopic imaging, high spatial resolution is achieved at the
      price of a large number of phase-encoding steps, leading to long acquisition
      times. Fast spatial encoding methods reduce the minimum total acquisition time.
      In this article, a k-space scanning scheme using a continuous series of growing
      and shrinking, or "out-and-in," spiral trajectories is implemented and the
      feasibility of spiral spectroscopic imaging for animal models at high B(0) field
      is demonstrated. This method was applied to rat brain at 7 T. With a voxel size
      of about 8.7 microl (as calculated from the point-spread function), a 30 x 30
      matrix, and a spectral bandwidth of 11 kHz, the minimum scan time was 9 min 20
      sec for a signal-to-noise ratio of 7.1 measured on the N-acetylaspartate peak.

PMID- 14648561
TI  - In vivo quantification of choline compounds in the breast with 1H MR
      spectroscopy.
AB  - This work describes a methodology for quantifying levels of total choline
      containing compounds (tCho) in the breast using in vivo (1)H MR spectroscopy
      (MRS) at high field (4 Tesla). Water is used as an internal reference compound to
      account for the partial volume of adipose tissue. Peak amplitudes are estimated
      by fitting one peak at a time over a narrow frequency band to allow measurement
      of small metabolite resonances in spectra with large lipid peaks. This
      quantitative method significantly improves previously reported analysis methods
      by accounting for the variable sensitivity of breast (1)H MRS measurements. Using
      this technique, we detected and quantified a tCho peak in 214 of 500 in vivo
      spectra. tCho levels were found to be significantly higher in malignancies than
      in benign abnormalities and normal breast tissues, which suggests that this
      technique could be used to diagnose suspicious lesions and monitor response to
      cancer treatments.

PMID- 14648562
TI  - Investigation of the microstructure of the isolated rat heart: a comparison
      between T*2- and diffusion-weighted MRI.
AB  - Myocardial fiber structure can be determined with diffusion-weighted (DW) MRI as
      well as with high-resolution T*(2) imaging. The purpose of the present study was
      twofold: to provide a more quantitative description of T*(2)-based myocardial
      fiber contrast, and to compare the T*(2)-based fiber structure with high
      resolution (78 microm in-plane, 1-mm slice thickness) DW images of the isolated
      rat heart at 11.75 T. This study demonstrates that the static dephasing regime is
      responsible for visualization of myocardial microstructure, and that the dynamic
      dephasing regime can be neglected. In comparison with DW experiments, T*(2)
      mapping and DW images yield almost equivalent information on myocardial fiber
      structure.

PMID- 14648563
TI  - Variation of the relaxographic "shutter-speed" for transcytolemmal water exchange
      affects the CR bolus-tracking curve shape.
AB  - Contrast reagents (CRs) may enter the tissue interstitium for a period after a
      vascular bolus injection. As the amount of interstitial CR increases, the
      longitudinal relaxographic NMR "shutter-speed" (T(-1)) for the equilibrium
      transcytolemmal water exchange process increases. The quantity T(-1) is given by
      |r(1o)[CR(o)] + R(1o0) - R(1i)| (where r(1o) and [CR(o)] represent the
      interstitial (extracellular) CR relaxivity and concentration, respectively, and
      R(1o0) and R(1i) are the extra- and intracellular (1)H(2)O relaxation rate
      constants, respectively, in the absence of exchange). The increase of T(-1) with
      [CR(o)] causes the kinetics of the water exchange equilibrium to appear to
      decrease. Here, analytical theory for two-site-exchange processes is combined
      with that for pharmacokinetic CR delivery, extraction, and distribution in a
      method termed BOLus Enhanced Relaxation Overview (BOLERO(Copyright )). The
      shutter-speed effect alters the shape of the bolus-tracking (B-T) time-course. It
      is shown that this is mostly accounted for by the inclusion of only one
      additional parameter, which measures the mean intracellular lifetime of a water
      molecule. Simulated and real data demonstrate that the effect of shutter-speed
      variation on pharmacokinetic parameters can be very significant: neglecting this
      effect can lead to an underestimation of the parameter values by 50%. This
      phenomenon can be heterogeneous. Within a tiny gliosarcoma implanted in the rat
      brain, the interstitial CR in the tumor core never rises to a level sufficient to
      cause apparent slowing of the exchange process. However, within the few microns
      needed to reach the proliferating rim, this occurs to a significant degree. Thus,
      even relative pharmacokinetic quantities can be incorrectly represented in a
      parametric map that neglects this effect. The BOLERO analysis shows promise for
      in vivo vascular phenotyping in pathophysiology. It also includes a provision for
      approximating the separation of the perfusion and permeability contributions to
      CR extravasation.

PMID- 14648564
TI  - Characterization of diffusing capacity and perfusion of the rat lung in a
      lipopolysaccaride disease model using hyperpolarized 129Xe.
AB  - The ability to quantify pulmonary diffusing capacity and perfusion using dynamic
      hyperpolarized (129)Xe NMR spectroscopy is demonstrated. A model of alveolar gas
      exchange was developed, which, in conjunction with (129)Xe NMR, enables
      quantification of average alveolar wall thickness, pulmonary perfusion, capillary
      diffusion length, and mean transit time. The technique was employed to compare a
      group of naive rats (n = 10) with a group of rats with acute inflammatory lung
      injury (n = 10), caused by instillation of lipopolysaccaride (LPS). The measured
      structural and perfusion-related parameters were in agreement with reported
      values from studies using non-NMR methods. Significant differences between the
      groups were found in total diffusion length (control 8.5 +/- 0.5 microm, LPS 9.9
      +/- 0.6 microm, P < 0.001), in capillary diffusion length (control 2.9 +/- 0.4
      microm, LPS 3.9 +/- 1.0 microm, P < 0.05), and in pulmonary hematocrit (control
      0.55 +/- 0.06, LPS 0.43 +/- 0.08, P < 0.01), whereas no differences were observed
      in alveolar wall thickness, pulmonary perfusion, and mean transit time. These
      results demonstrate the ability of the method to distinguish two main aspects of
      lung function, namely, diffusing capacity and pulmonary perfusion.

PMID- 14648565
TI  - Influence of magnetically-induced E-fields on cardiac electric activity during
      MRI: A modeling study.
AB  - In modern magnetic resonance imaging (MRI), patients are exposed to strong, time
      varying gradient magnetic fields that may be able to induce electric fields (E
      fields)/currents in tissues approaching the level of physiological significance.
      In this work we present theoretical investigations into induced E-fields in the
      thorax, and evaluate their potential influence on cardiac electric activity under
      the assumption that the sites of maximum E-field correspond to the myocardial
      stimulation threshold (an abnormal circumstance). Whole-body cylindrical and
      planar gradient coils were included in the model. The calculations of the induced
      fields are based on an efficient, quasi-static, finite-difference scheme and an
      anatomically realistic, whole-body model. The potential for cardiac stimulation
      was evaluated using an electrical model of the heart. Twelve-lead
      electrocardiogram (ECG) signals were simulated and inspected for arrhythmias
      caused by the applied fields for both healthy and diseased hearts. The
      simulations show that the shape of the thorax and the conductive paths
      significantly influence induced E-fields. In healthy patients, these fields are
      not sufficient to elicit serious arrhythmias with the use of contemporary
      gradient sets. However, raising the strength and number of repeated switching
      episodes of gradients, as is certainly possible in local chest gradient sets,
      could expose patients to increased risk. For patients with cardiac disease, the
      risk factors are elevated. By the use of this model, the sensitivity of cardiac
      pathologies, such as abnormal conductive pathways, to the induced fields
      generated by an MRI sequence can be investigated.

PMID- 14648566
TI  - Automated segmentation and analysis of vascular structures in magnetic resonance
      angiographic images.
AB  - The accurate assessment of the presence and extent of vascular disease, and
      planning of vascular interventions based on MRA requires the determination of
      vessel dimensions. The current standard is based on measuring vessel diameters on
      maximum intensity projections (MIPs) using calipers. In order to increase the
      accuracy and reproducibility of the method, automated analysis of the 3D MR data
      is required. A novel method for automatically determining the trajectory of the
      vessel of interest, the luminal boundaries, and subsequent the vessel dimensions
      is presented. The automated segmentation in 3D uses deformable models, combined
      with knowledge of the acquisition protocol. The trajectory determination was
      tested on 20 in vivo studies of the abdomen and legs. In 93% the detected
      trajectory followed the vessel. The luminal boundary detection was validated on
      contrast-enhanced (CE) MRA images of five stenotic phantoms. The results from the
      automated analysis correlated very well with the true diameters of the phantoms
      used in the in vitro study (r = 0.999, P < 0.001). MRA and x-ray angiography (XA)
      of the phantoms also correlated well (r = 0.895, P < 0.001). The average unsigned
      difference between the MRA and XA measurements was 0.08 +/- 0.05 mm. In
      conclusion, the automated approach allows the accurate assessment of vessel
      dimensions in MRA images.

PMID- 14648567
TI  - Quantitative assessment of carotid plaque composition using multicontrast MRI and
      registered histology.
AB  - MRI is emerging as a promising modality for monitoring carotid atherosclerosis.
      Multiple MR contrast weightings are required for identification of plaque
      constituents. In this study, eight MR contrast weightings with proven potential
      for plaque characterization were used to image carotid endarterectomy specimens.
      A classification technique was developed to create a tissue-specific map by
      incorporating information from all MR contrast weightings. The classifier was
      validated by comparison with micro-CT (calcification only) and with matched
      histological slices registered to MR images using a nonlinear warping algorithm
      (other components). A pathologist who was blinded to the classifier results
      manually segmented digitized histological images. The sensitivity of the
      classifier, as determined by pixel-by-pixel comparison with the pathologist's
      segmentation and micro-CT, was 60.4% for fibrous tissue, 83.9% for necrosis,
      97.6% for calcification, and 65.2% for loose connective tissue. The corresponding
      values for specificity were 87.9%, 75.0%, 98.3%, and 94.9%, respectively. In
      conclusion, multicontrast MRI was successfully used in conjunction with a
      supervised classification algorithm to identify plaque components in
      endarterectomy specimens. Furthermore, this methodology will provide a framework
      for comparing different classification algorithms, and determining which
      combination of MR contrasts will be most valuable for in vivo plaque imaging.

PMID- 14648568
TI  - Sickle red blood cells accumulate in tumor.
AB  - The preferential accumulation of sickle blood cells in tumor vasculature is
      demonstrated noninvasively using MRI and sickle red blood cells loaded with Gd
      DTPA and invasively by two other techniques. The distribution of red blood cells
      in rat brain tumors relative to normal brains were measured using three separate
      techniques: MRI of Gd-DTPA loaded cells, fluorescent microscopy detection of
      Oregon Green 488 fluorescence conjugated to a streptavidin-biotin complex that
      binds to red blood cell surface proteins, and autoradiography using a technetium
      (99m)Tc-labeling kit. Labeled red cells were infused intravenously in rats with
      brain tumors. Sickle cells preferentially accumulated in tumor relative to normal
      brain, with highest concentrations near the tumor / normal tissue boundary,
      whereas control normal red cells did not preferentially aggregate at the tumor
      periphery. This demonstrates the potential of sickle red blood cells to
      accumulate in the abnormal tumor vessel network, and the ability to detect their
      aggregation noninvasively and at high spatial resolution using MRI. The
      application of the noninvasive measurement of sickle cells for imaging tumor
      neovasculature, or as a delivery tool for therapy, requires further study.

PMID- 14648569
TI  - Multishot partial-k-space EPI for high-resolution fMRI demonstrated in a rat
      whisker barrel stimulation model at 3T.
AB  - A multishot partial-k-space EPI technique is presented and validated by fMRI at
      high spatial resolution. High-resolution phase maps corrected by phase-encoded
      reference scans have less off-resonance effects. Phantom studies demonstrate that
      this method can substantially improve partial-k-space EPI image formation. BOLD
      fMRI at submillimeter spatial resolution (156 x 156 x 2000 microm(3), 0.049
      microl) was achieved in a rat whisker barrel stimulation model using this
      technique. The study included eight rats, five of which were administered an
      intravascular contrast agent (monocrystalline iron oxide nanocolloid (MION))
      after the BOLD experiments. In two rats the highest BOLD responses were in the
      deep layers (IV-VI), and in six rats the highest responses were on the surface
      and in the deep cortical layers. Most of the pixels that exhibited high BOLD
      responses had high blood volume weightings. The benefits of this technique are
      expected to increase for high-resolution fMRI at higher magnetic fields, where
      T(2) (*) is shorter.

PMID- 14648570
TI  - Whole-heart steady-state free precession coronary artery magnetic resonance
      angiography.
AB  - Current implementations of coronary artery magnetic resonance angiography (MRA)
      suffer from limited coverage of the coronary arterial system. Whole-heart
      coronary MRA was implemented based on a free-breathing steady-state free
      precession (SSFP) technique with magnetization preparation. The technique was
      compared to a similar implementation of conventional, thin-slab coronary MRA in
      12 normal volunteers. Three thin-slab volumes were prescribed: 1) a transverse
      slab, covering the left main (LM) artery and proximal segments of the left
      anterior ascending (LAD) and left circumflex (LCX) coronary arteries; 2) a double
      oblique slab covering the right coronary artery (RCA); and 3) a double-oblique
      slab covering the proximal and distal segments of the LCX. The whole-heart data
      set was reformatted in identical orientations. Visible vessel length, vessel
      sharpness, and vessel diameter were determined and compared separately for each
      vessel. Whole-heart coronary MRA visualized LM/LAD (11.7 +/- 3.4 cm) and LCX (6.9
      +/- 3.6 cm) over a significantly longer distance than the transverse volume
      (LM/LAD, 6.1 +/- 1.1 cm, P < 0.001; LCX, 4.2 +/- 1.2 cm, P < 0.05). Improvements
      in visible vessel length for RCA and LCX in the whole-heart approach vs. their
      respective targeted volumes were not significant. It is concluded that the whole
      heart coronary MRA technique improves visible vessel length and facilitates high
      quality coronary MRA of the complete coronary artery tree in a single
      measurement.

PMID- 14648571
TI  - Femoro-tibial cartilage metrics from coronal MR image data: Technique, test
      retest reproducibility, and findings in osteoarthritis.
AB  - MRI-based measures of cartilage morphology are being increasingly used as
      surrogate markers in osteoarthritis. In contrast to other knee joint surfaces,
      quantitative analysis of the femoral condyles from sagittal MRI suffers from
      limited precision. The objective, therefore, was to develop a technique for
      reproducible assessment of femoral cartilage morphology from coronal image data.
      Coronal MR images (3D T(1)-w FLASHwe) of the knee were obtained in 16 healthy
      volunteers and in 7 patients with severe osteoarthritis (OA, prior to knee
      arthroplasty), with repositioning between repeated scans. After segmentation the
      cartilage volume, thickness, and joint surface areas were quantified in the tibia
      and in an anatomically defined region of the femoral condyle. Immediate test
      retest interscan precision errors (CV%) for femoral cartilage volume were 3.0%
      (SD = 26 microl) and 3.2% (29 microl) medially and laterally in volunteers, and
      3.0% (34 microl) and 7.0% (37 microl) in OA patients. The estimated loss, from
      cross sectional data, in the patients in the medial femoral condyle (-61%/-4.4
      SD) was higher than that in the medial tibia (-45%/-3.1 SD) and compared
      favorably with precision errors (ratio > 16:1). The technique proposed overcomes
      some of the problems associated with sagittal scans and thus shows high promise
      for reliable assessment of femoro-tibial cartilage loss in OA.

PMID- 14648572
TI  - Quantification of bolus-tracking MRI: Improved characterization of the tissue
      residue function using Tikhonov regularization.
AB  - Quantification of cerebral blood flow (CBF) and the tissue residue function (R)
      using bolus-tracking MRI requires deconvolution of the arterial input function
      (AIF). Currently, the most commonly used deconvolution method is singular value
      decomposition (SVD), which has been shown to produce accurate estimations of CBF.
      However, this method introduces unwanted oscillations in the time course of R,
      and there are situations in which the actual shape is of interest (e.g., in
      calculating flow heterogeneity and assessing bolus dispersion). In such cases,
      the conventional SVD method may no longer be suitable, and an alternative
      approach may be required. This work describes the implementation of Tikhonov
      regularization with the L-curve criterion to quantify CBF and obtain a better
      characterization of R. The methodology is tested on simulated and patient data,
      and the results are compared to those found using the conventional SVD approach.
      Although both methods produce similar CBF values, the deconvolved R shape
      obtained using SVD is dominated by oscillations and fails to characterize the
      shape in the presence of dispersion. On the other hand, the use of the proposed
      regularization method improves the characterization of the tissue residue
      function.

PMID- 14648573
TI  - Real-time volumetric flow measurements with complex-difference MRI.
AB  - Blood flow in large vessels can be noninvasively evaluated with phase-contrast
      (PC) MRI by encoding the spin velocity to the image phase. Conventional phase
      difference processing of the flow-encoded image data yields velocity images.
      Complex-difference processing is an alternative to phase-difference methods, and
      has the advantage of eliminating signal from stationary spins. In this study, two
      acquisitions with differential flow encoding are subtracted to yield a single
      projection that contains signal from only those spins moving in the direction of
      the flow-encoding gradients. The increase in acquisition efficiency allows real
      time flow imaging with a temporal window as short as two acquisition lengths (60
      ms). Validation of the complex-difference method by comparison with conventional
      gated-segmented PC-MRI in a flow phantom yielded a correlation of r > 0.99. Peak
      arterial flow rates in the popliteal artery and desending aorta measured in vivo
      with the complex-difference method were 0.92 +/- 0.06 of the values measured with
      conventional PC imaging. Real-time in vivo volumetric flow imaging of transient
      flow events is also presented.

PMID- 14648574
TI  - Shear stiffness estimation using intravoxel phase dispersion in magnetic
      resonance elastography.
AB  - Dynamic MR elastography (MRE) is a phase-contrast technique in which the periodic
      shear motion of an object is encoded as variations in the phase of the
      reconstructed images. An alternative MRE method is presented whereby waves are
      depicted as intensity variations in the magnitude images due to intravoxel phase
      dispersion (IVPD). A theoretical framework is developed to model how the IVPD
      magnitude data are related to the underlying shear wave motion, and how they can
      be used to estimate shear stiffness. The results are shown in a series of phantom
      experiments to demonstrate that IVPD MRE complements phase-contrast MRE.

PMID- 14648575
TI  - Efficient k-space sampling by density-weighted phase-encoding.
AB  - Acquisition-weighting improves the localization of MRI experiments. An approach
      to acquisition-weighting in a purely phase-encoded experiment is presented that
      is based on a variation of the sampling density in k-space. In contrast to
      conventional imaging or to accumulation-weighting, where k-space is sampled with
      uniform increments, density-weighting varies the distance between neighboring
      sampling points Deltak to approximate a given radial weighting function. A fast,
      noniterative algorithm has been developed to calculate the sampling matrix in
      one, two, and three dimensions from a radial weighting function w(k), the desired
      number of scans NA(tot) and the nominal spatial resolution Deltax(nom). Density
      weighted phase-encoding combines the improved shape of the spatial response
      function and the high SNR of acquisition-weighting with an extended field of
      view. The artifact energy that results from aliasing due to a small field of view
      is substantially reduced. The properties of density-weighting are compared to
      uniform and to accumulation-weighted phase-encoding in simulations and
      experiments. Density-weighted (31)P 3D chemical shift imaging of the human heart
      is shown which demonstrates the superior performance of density-weighted
      metabolic imaging.

PMID- 14648576
TI  - Fast 3D imaging using variable-density spiral trajectories with applications to
      limb perfusion.
AB  - Variable-density k-space sampling using a stack-of-spirals trajectory is proposed
      for ultra fast 3D imaging. Since most of the energy of an image is concentrated
      near the k-space origin, a variable-density k-space sampling method can be used
      to reduce the sampling density in the outer portion of k-space. This
      significantly reduces scan time while introducing only minor aliasing artifacts
      from the low-energy, high-spatial-frequency components. A stack-of-spirals
      trajectory allows control over the density variations in both the k(x)-k(y) plane
      and the k(z) direction while fast k-space coverage is provided by spiral
      trajectories in the k(x)-k(y) plane. A variable-density stack-of-spirals
      trajectory consists of variable-density spirals in each k(x)-k(y) plane that are
      located in varying density in the k(z) direction. Phantom experiments demonstrate
      that reasonable image quality is preserved with approximately half the scan time.
      This technique was then applied to first-pass perfusion imaging of the lower
      extremities which demands very rapid volume coverage. Using a variable-density
      stack-of-spirals trajectory, 3D images were acquired at a temporal resolution of
      2.8 sec over a large volume with a 2.5 x 2.5 x 8 mm(3) spatial resolution. These
      images were used to resolve the time-course of muscle intensity following
      contrast injection.

PMID- 14648577
TI  - New hybrid technique for accurate and reproducible quantitation of dynamic
      contrast-enhanced MRI data.
AB  - The accuracy and precision of two major approaches for analyzing dynamic MRI data
      from the first passage of a Gd-DTPA contrast bolus are examined, using a Monte
      Carlo simulation. Method 1 fits the contrast concentration curve of the first
      pass to a two-compartment kinetic model to determine the tissue pharmacokinetic
      parameters. Method 2 decomposes intravascular and interstitial components of the
      first-pass curve based on a leakage profile (LP) model. Based on the results of
      these Monte Carlo simulations, a new "hybrid" method is proposed that combines
      both analytical approaches to optimize accuracy and precision of estimates of
      K(trans), v(e), and v(p). The new method was evaluated by computer simulation and
      used on experimental results from a patient with primary brain tumors. The new
      method has the potential to provide more accurate quantification of tissue plasma
      volume and vessel permeability.

PMID- 14648578
TI  - Comparison of longitudinal metabolite relaxation times in different regions of
      the human brain at 1.5 and 3 Tesla.
AB  - In vivo longitudinal relaxation times of N-acetyl compounds (NA), choline
      containing substances (Cho), creatine (Cr), myo-inositol (mI), and tissue water
      were measured at 1.5 and 3 T using a point-resolved spectroscopy (PRESS) sequence
      with short echo time (TE). T(1) values were determined in six different brain
      regions: the occipital gray matter (GM), occipital white matter (WM), motor
      cortex, frontoparietal WM, thalamus, and cerebellum. The T(1) relaxation times of
      water protons were 26-38% longer at 3 T than at 1.5 T. Significantly longer
      metabolite T(1) values at 3 T (11-36%) were found for NA, Cho, and Cr in the
      motor cortex, frontoparietal WM, and thalamus. The amounts of GM, WM, and
      cerebrospinal fluid (CSF) within the voxel were determined by segmentation of a
      3D image data set. No influence of tissue composition on metabolite T(1) values
      was found, while the longitudinal relaxation times of water protons were strongly
      correlated with the relative GM content.

PMID- 14648579
TI  - Optimized detection of changes in glucose-6-phosphate levels in human skeletal
      muscle by 31P MR spectroscopy.
AB  - As glucose-6-phosphate (G6P) plays a central role in muscle energy metabolism,
      the possibility to observe changes in the tissue level of this compound in vivo
      is very relevant. G6P can be detected noninvasively by (31)P MR spectroscopy, but
      its visibility in vivo is severely hampered due to low tissue levels and spectral
      overlap with other, stronger phosphomonoester signals. To optimize the
      observation of changes in G6P levels in human calf muscle by (31)P MR
      spectroscopy at 1.5 T, we implemented an approach involving a new RF probe and a
      postacquisition correction method. An anatomically shaped circularly polarized
      (31)P coil was designed for high intrinsic sensitivity. Together with an
      additional (1)H coil and (1)H blocking circuits this allowed the application of
      NOE and (1)H decoupling to further enhance sensitivity. A hyperglycemic
      hyperinsulinemic clamp was used to increase G6P levels. The spectra were
      corrected for frequency and phase drift due to scanner instability and leg
      movements using an automated phase and frequency correction method. Difference
      (31)P spectroscopy was applied to detect changes of the G6P signal. The result,
      in five healthy subjects, demonstrated that the combination of sensitivity
      optimization with automated drift correction enabled a robust detection of G6P
      changes in time series experiments down to a resolution of 10 min.

PMID- 14648580
TI  - Proton high-resolution magic angle spinning NMR analysis of fresh and previously
      frozen tissue of human prostate.
AB  - The previously observed improvement in spectral resolution of tissue proton NMR
      with high-resolution magic angle spinning (HRMAS) was speculated to be due
      largely to freeze-thawing artifacts resulting from tissue storage. In this study,
      12 human prostate samples were analyzed on a 14.1T spectrometer at 3 degrees C,
      with HRMAS rates of 600 and 700 Hz. These samples were measured fresh and after
      they were frozen for 12-16 hr prior to thawing. The spectral linewidths measured
      from fresh and previously frozen samples were identical for all metabolites
      except citrate and acetate. The metabolite intensities of fresh and freeze-thawed
      samples depend on the quantification procedures used; however, in this experiment
      the differences of means were <30%. As expected, it was found that tissue storage
      impacts tissue quality for pathological analysis, and HRMAS conditions alone are
      not sufficiently destructive to impair pathological evaluation. Furthermore,
      although storage conditions affect absolute metabolite concentrations in NMR
      analysis, relative metabolite concentrations are less affected.

PMID- 14648581
TI  - Contribution of mitochondria to cardiac muscle water/macromolecule proton
      magnetization transfer.
AB  - The contribution of mitochondria to water-macromolecule proton magnetization
      transfer (MT) was evaluated in porcine heart tissue. An examination of isolated
      mitochondria in suspension, at the same concentration as found in heart tissue,
      revealed MT effects very similar in magnitude and bandwidth to those in intact
      heart tissue. Disruption of the gross structure of the mitochondria by freeze
      thawing or with detergent resulted in only approximately 25% decreases in MT,
      which suggests that the structure of the mitochondria is not critical for these
      effects. The current data indicate that mitochondria macromolecules contribute
      significantly to MT in the intact heart.

PMID- 14648582
TI  - Catheter-directed contrast-enhanced coronary MR angiography in swine using
      magnetization-prepared True-FISP.
AB  - Contrast-enhanced (CE) coronary magnetic resonance angiography (MRA) following
      intraarterial (IA) injection of contrast agent was compared using two sequences
      in swine: magnetization-prepared fast imaging with steady-state precession (True
      FISP), and magnetization-prepared fast low-angle shot (FLASH). Thick-slice
      projection images were acquired with submillimeter in-plane spatial resolution
      (0.9 x 0.8 mm(2)). The magnetization-preparation scheme provided a clear
      delineation of the major coronary arteries with excellent background suppression.
      The True-FISP acquisition resulted in an increase in signal-to-noise ratio (SNR)
      and contrast-to-noise ratio (CNR) by approximately a factor of 2 over FLASH (P <
      0.05). Magnetization-prepared True-FISP is a promising technique for catheter
      directed CE thick-slice projection coronary MRA.

PMID- 14648584
TI  - Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix
      metalloproteinases in the central nervous system.
AB  - Astrocytes are intimately involved in the mechanisms of neural injury and repair.
      They participate in a variety of homeostatic functions and elicit repair
      responses as balance mechanisms. Currently, there is a growing appreciation of a
      more active role of astrocytes in neuronal signaling and function. One key
      homeostatic mechanism of astrocytes in tissue repair is maintained through their
      production of tissue inhibitors of metalloproteinases (TIMPs). The family of
      TIMPs (1-4) plays a central regulatory role as inhibitors of matrix
      metalloproteinases (MMPs), enzymes involved in extracellular matrix maintenance
      and remodeling. Recently, TIMP-1, the inducible form, has been identified as a
      multifunctional molecule with divergent functions. It participates in wound
      healing and regeneration, cell morphology and survival, tumor metastasis,
      angiogenesis, and inflammatory responses. An imbalance of MMP/TIMP regulation has
      been implicated in several inflammatory diseases of the central nervous system
      (CNS). Here we review the conundrums of TIMP-1 regulation in CNS pathophysiology.
      We propose that astrocyte-TIMP-1 may play an important role in CNS homeostasis
      and disease. Astrocyte TIMP-1 expression is differentially regulated in
      inflammatory neurodegenerative diseases and may have significant therapeutic
      relevance.

PMID- 14648585
TI  - Distribution of polysialylated neural cell adhesion molecule in rat septal nuclei
      and septohippocampal pathway: transient increase of polysialylated interneurons
      in the subtriangular septal zone during memory consolidation.
AB  - During memory consolidation neuroplastic events in the mediotemporal
      corticohippocampal pathway are accompanied by transient increases in the
      frequency of neurons expressing polysialylated neural cell adhesion molecule
      (NCAM PSA), a posttranslational modification associated with morphofunctional
      change. As a bidirectional pathway between the hippocampus and the septal nuclei
      also influences memory processing, we have determined the distribution of NCAM
      PSA within this system before and after learning in the adult Wistar rat. The
      most intense NCAM PSA immunoreactivity was observed in the medial and triangular
      septal nuclei, regions that regulate hippocampal theta rhythm during memory
      consolidation. Within the fimbria, NCAM PSA was expressed only in a subpopulation
      of fibres, most likely cholinergic projections from the medial septum to the
      hippocampus. Grey level analysis or direct cell counting revealed no learning
      specific change in NCAM PSA expression in these septal subregions after avoidance
      conditioning or spatial training. A population of discrete polysialylated neurons
      in the subtriangular septal zone, however, exhibited a transient twofold
      frequency increase at 12 hr after training in either task. Immunohistochemical
      analysis revealed these cells to be gamma-aminobutyric acid (GABAergic)
      interneurons co-expressing vasoactive intestinal peptide. The unique location of
      these interneurons is proposed to provide a natural plexus by which bidirectional
      communication between the septum and hippocampus may be modified during memory
      consolidation.

PMID- 14648586
TI  - DNA microarray cluster analysis reveals tissue similarity and potential neuron
      specific genes expressed in cranial sensory ganglia.
AB  - Each of four cranial sensory ganglia, trigeminal, geniculate, petrosal, and
      nodose ganglia, contains multiple kinds of sensory neurons with different cell
      morphologies and neuronal properties that transmit information about sensory
      stimuli received peripherally. Here we analyze the complex properties of these
      neurons from the viewpoint of gene expression using DNA microarrays by cluster
      analysis. From a total of 8,740 genes, 498 genes were selected as showing tissue
      dependent expression on the microarray by hierarchical cluster analysis, and
      their profiles indicated that, among the four sensory ganglia, the petrosal and
      trigeminal ganglia are intimately related. Tissue trees of 37 subclusters
      containing the 498 genes showed that the profiles of gene expression and the
      subclusters were classified into a smaller number of groups (18 groups) when
      information on the amounts of expression was added. In situ hybridization
      analysis of 21 genes selected from 13 different groups was carried out, and the
      gene expression patterns were classified into eight categories. The putative
      profiles postulated from the microarray data were essentially consistent with the
      patterns of expression at the cellular level as shown by in situ hybridization.
      In conclusion, from the overall analyses of gene expression by DNA microarray, we
      can identify a number of candidate genes showing neuron type-specific expression
      in the peripheral ganglia.

PMID- 14648587
TI  - Dual role of cyclic AMP-dependent protein kinase in neuritogenesis and
      synaptogenesis during neuronal differentiation.
AB  - To create precise neural circuits in the nervous system, neuritogenesis and
      synaptogenesis are the critical cellular processes during neuronal
      differentiation. We examined the cyclic AMP (cAMP)-responsible signaling pathways
      for regulating neuritogenesis and synaptogenesis in NG108-15 cells. A rise in
      intracellular cAMP concentration by a membrane-permeable cAMP analog, dibutyryl
      cAMP (DBcAMP), led to an increase in the number of neurites and varicosities.
      Inhibition of cAMP-dependent protein kinase (PKA) activity by a PKA inhibitor
      (H89) accelerated this neuritogenesis and neurite outgrowth rate. Treatment with
      H89, however, decreased the number of varicosities and the frequency of
      postsynaptic miniature current recorded in the cultured cells, resulting in
      suppression of synaptogenesis. Immunoblot analyses revealed that PKA activity
      mediates phosphorylation of a gene transcription factor, cAMP-response element
      binding protein (CREB). On the other hand, inhibition of a mitogen-activated
      protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway by a
      MAPK/ERK kinase (MEK) inhibitor (PD98059) suppressed both neuritogenesis and
      neurite outgrowth without CREB phosphorylation. These results suggest strongly
      that PKA simultaneously plays two different roles in neuronal differentiation:
      inhibition of neuritogenesis and stimulation of synaptogenesis, via CREB-mediated
      gene expression.

PMID- 14648588
TI  - Isolation and characterization of neural progenitor cells from post-mortem human
      cortex.
AB  - Post-mortem human brain tissue represents a vast potential source of neural
      progenitor cells for use in basic research as well as therapeutic applications.
      Here we describe five human neural progenitor cell cultures derived from cortical
      tissue harvested from premature infants. Time-lapse videomicrography of the
      passaged cultures revealed them to be highly dynamic, with high motility and
      extensive, evanescent intercellular contacts. Karyotyping revealed normal
      chromosomal complements. Prior to differentiation, most of the cells were nestin,
      Sox2, vimentin, and/or GFAP positive, and a subpopulation was doublecortin
      positive. Multilineage potential of these cells was demonstrated after
      differentiation, with some subpopulations of cells expressing the neuronal
      markers beta-tubulin, MAP2ab, NeuN, FMRP, and Tau and others expressing the
      oligodendroglial marker O1. Still other cells expressed the classic glial marker
      glial fibrillary acidic protein (GFAP). RT-PCR confirmed nestin, SOX2, GFAP, and
      doublecortin expression and also showed epidermal growth factor receptor and
      nucleostemin expression during the expansion phase. Flow cytometry showed high
      levels of the neural stem cell markers CD133, CD44, CD81, CD184, CD90, and CD29.
      CD133 markedly decreased in high-passage, lineage-restricted cultures.
      Electrophysiological analysis after differentiation demonstrated that the
      majority of cells with neuronal morphology expressed voltage-gated sodium and
      potassium currents. These data suggest that post-mortem human brain tissue is an
      important source of neural progenitor cells that will be useful for analysis of
      neural differentiation and for transplantation studies.

PMID- 14648589
TI  - Two types of VIP neuronal components in rat suprachiasmatic nucleus.
AB  - Vasoactive intestinal peptide (VIP) neurons constitute a large group in the
      suprachiasmatic nucleus (SCN) and it is thought that they are involved in the
      generation and entrainment of circadian rhythm. We have characterized these VIP
      expressing neurons in rat SCN by their ability to induce the mammalian Period1
      (Per1) gene in response to light exposure, innervation of retinal afferents, day
      night variations in VIP mRNA, and coexpression of gastrin releasing peptide
      (GRP). VIP neurons in the ventrolateral SCN (SCNVL) were subdivided into two
      groups, light-evoked Per1-inducible main SCNVL (SCNVLmain) and non-Per1-inducible
      medially located SCNVL (SCNVLmed). Retinal innervation was abundant in the
      SCNVLmain but nearly absent in the SCNVLmed. Day-night variation in VIP mRNA
      expression level was observed in the SCNVLmain but not in the SCNVLmed. GRP mRNA
      was seen in rarely SCNVLmed but abundant in SCNVLmain, where some neurons
      coexpressed VIP mRNA. These findings indicate that VIP neurons in the SCN can be
      divided into two topographically and functionally distinct groups.

PMID- 14648590
TI  - Role for TGF-beta1, FGF-2 and PDGF-AA in a myelination of CNS aggregate cultures
      enriched with macrophages.
AB  - The increase in myelin basic protein (MBP) synthesis observed in brain aggregate
      cultures supplemented with macrophages is reflected in elevated supernatant
      protein levels of the key promoters of oligodendrocyte proliferation, fibroblast
      growth factor-2 (FGF-2) and platelet-derived growth factor-AA (PDGF-AA), during
      the premyelinating phase. Although supernatant levels of transforming growth
      factor-beta1 (TGF-beta1), the most abundant growth factor produced at the
      transcriptional and translational levels by phagocytic macrophages, were reduced
      at this stage, it was the only growth factor for which mRNA expression was
      increased significantly in macrophage-enriched cultures. TGF-beta1, which
      supports oligodendrocyte differentiation, was increased in the supernatant of
      macrophage-enriched cultures only after the onset of myelinogenesis. Hence,
      standard cultures treated with TGF-beta1 during the premyelinating period
      reproduced effects of macrophage supplementation, inducing an increase in MBP
      synthesis and in PDGF-AA and FGF-2 bioavailability. A similar increase in MBP
      synthesis in PDGF-AA treated cultures emphasises its central role in
      oligodendrocyte progenitor proliferation. In contrast, FGF-2 blocked MBP
      synthesis in the cultures. In cultures treated with anti-TGF-beta1 antibody
      before or after the first detection of MBP, supernatant levels of TGF-beta1, FGF
      2, and PDGF-AA were reduced with resultant inhibition of myelination.
      Paradoxically, supraphysiological TGF-beta1 treatment after the onset of
      myelination had the same effect on myelin accumulation. These results indicate an
      enabling and regulatory role for TGF-beta1 in oligodendrocyte development and, as
      a source of TGF-beta1, macrophages in the inflammatory multiple sclerosis lesion,
      may have the potential to promote remyelination by modulating the growth factor
      repertoire in demyelinating disease.

PMID- 14648591
TI  - Constitutive expression of p21H-Ras(Val12) in neurons induces increased axonal
      size and dendritic microtubule density in vivo.
AB  - The small G protein p21Ras is a key signal transducer mediating cellular growth
      and proliferation responses to extracellular stimuli. We investigated by electron
      microscopy the effects of augmented p21Ras activity on neuronal processes and
      microtubule arrangement in vivo. We used transgenic mice with a neuron-specific
      overexpression of p21H-RasVal12, which starts postnatally around Day 15. Axonal
      and dendritic diameters and the numerical density of dendritic microtubules were
      analyzed at postnatal Day 12 before the onset of transgene expression and in
      adult mice. In adult transgenic mice, calibers of both axons (corpus callosum)
      and dendrites (layers II/III of somatosensory cortex) were enlarged by about 57%
      and 79%, respectively. The increase in dendritic calibers was associated with an
      increment in the amount of microtubules. Even in dendrites of equivalent
      diameters, the number of microtubules was higher in transgenic mice compared to
      that in wild-type mice suggesting an elevated microtubule density. Changes in
      process diameters or microtubule density were not observed at postnatal Day 12
      before relevant transcription of transgenic p21H-RasVal12. The present results
      extend previous findings on neuronal hypertrophy as a consequence of p21H
      RasVal12 expression and suggest a profound influence on the dendritic microtubule
      network.

PMID- 14648592
TI  - Changing sensitivity to cell death during development of retinal photoreceptors.
AB  - Photoreceptor cell death occurs during both normal and pathological retinal
      development. We tested for selective induction and blockade of cell death in
      either retinal photoreceptors or their precursors. Organotypical retinal explants
      from rats at postnatal days 3-11 were treated in vitro for 24 hr with
      thapsigargin, okadaic acid, etoposide, anisomycin, or forskolin. Explant sections
      were examined for cell death, and identification of either photoreceptors or
      proliferating/immediate postmitotic cells followed imunohistochemistry for either
      rhodopsin or bromodeoxyuridine and proliferating cell nuclear antigen,
      respectively. Photoreceptor cell death was selectively induced by either
      thapsigargin or okadaic acid, whereas death of proliferating/immediate
      postmitotic cells was induced by etoposide. Prelabeling of proliferating
      precursors allowed direct demonstration of changing sensitivity of photoreceptors
      to various chemicals. Degeneration of both photoreceptors and
      proliferating/immediate postmitotic cells depended on protein synthesis. Increase
      of intracellular cyclic AMP blocked degeneration of postmitotic, but not of
      proliferating, photoreceptor precursors. The selective induction and blockade of
      cell death show that developing photoreceptors undergo progressive changes in
      mechanisms of programmed cell death associated with phenotypic differentiation.

PMID- 14648593
TI  - p38 mitogen-activated protein kinase modulates expression of tumor necrosis
      factor-related apoptosis-inducing ligand induced by interferon-gamma in fetal
      brain astrocytes.
AB  - This study describes the involvement of the p38 mitogen-activated protein kinase
      (MAPK) during interferon-gamma (IFN-gamma) signaling in fetal brain astrocytes.
      In some pathological conditions of brain, p38 MAPK transduces stress-related
      signals, increases expression of proinflammatory cytokines, and induces cellular
      damage or apoptosis. In astrocytes, the tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL) expression level was increased by IFN-gamma.
      AG490, a JAK inhibitor, blocked TRAIL expression induced by IFN-gamma. SB203580,
      a specific p38alpha and p38beta2 MAPK inhibitor, decreased the TRAIL expression
      induced by IFN-gamma. The phosphorylation of the Ser727 site of STAT1, but not
      the Tyr701 site, was inhibited by SB203580. These results suggest that p38 MAPK
      modulates STAT1 phosphorylation in IFN-gamma signaling in fetal brain astrocytes.

PMID- 14648594
TI  - Suppression of ammonia-induced astrocyte swelling by cyclosporin A.
AB  - Brain edema is a serious complication of hepatic encephalopathy associated with
      fulminant hepatic failure (FHF). A major component of the edema seems to be
      cytotoxic, involving astrocyte swelling. Although the mechanism of brain edema in
      FHF is incompletely understood, it is generally believed that ammonia is involved
      critically in this process. Recent studies have shown that exposure of cultured
      astrocytes to ammonia results in the mitochondrial permeability transition (MPT),
      a phenomenon associated with mitochondrial failure and subsequent cellular
      dysfunction. The present study examined the potential role of the MPT in the
      astrocyte swelling associated with ammonia toxicity. Treatment of cultured
      astrocytes with ammonia (5 mM) caused a time-dependent increase in astrocyte cell
      volume (swelling), which was completely inhibited by the MPT inhibitor
      cyclosporin A (CsA). In this study, CsA also inhibited the ammonia-induced
      aquaporin 4 (AQP4) upregulation, which had been shown previously to be increased
      in cultured astrocytes by ammonia treatment. These findings suggest that the MPT
      plays a significant role in the ammonia-induced astrocyte swelling and may
      contribute to the brain edema associated with FHF.

PMID- 14648595
TI  - Microglial cell cycle-associated proteins control microglial proliferation in
      vivo and in vitro and are regulated by GM-CSF and density-dependent inhibition.
AB  - Hyperplasia of microglia is one characteristic of reactive gliosis, which is
      observed in various pathologic conditions in the central nervous system (CNS). To
      investigate the regulation mechanisms of microglial proliferation, the effect of
      granulocyte macrophage colony-stimulating factor (GM-CSF) on the expression of
      cell cycle-associated proteins was examined in the microglial cell line GMI-M6-3.
      After GM-CSF administration, cyclins D1, E, and A and cyclin-dependent kinase
      inhibitor p21Cip1 were increased, and another cyclin-dependent kinase inhibitor,
      p27Kip1, was decreased with morphologic transformation into ameboid form. By
      contrast, downregulation of these cyclins and p21Cip1, and strong upregulation of
      p27Kip1 accompanied by ramification were observed with GM-CSF deprivation. We
      also found that GMI-M6-3 exhibited homotypic contact inhibition of proliferation
      without any morphologic transformation. The increase of p27Kip1 and the decrease
      of cyclin A were suggested to play an important role in microglial contact
      inhibition. In addition, the direct effect of p27Kip1 to inhibit microglial
      proliferation was demonstrated both in vitro and in vivo by overexpression of
      p27Kip1.

PMID- 14648596
TI  - Proteasome inhibition arrests neurite outgrowth and causes "dying-back"
      degeneration in primary culture.
AB  - Proteasome inhibitors such as lactacystin were first isolated when assaying their
      ability to stimulate neurite outgrowth in neuronal-like cell lines; however,
      their effect on neurites in primary culture has been largely neglected. We report
      here that lactacystin causes immediate arrest of nerve growth factor (NGF)
      stimulated neurite outgrowth in sympathetic and sensory explant cultures. This is
      followed by neurite degeneration that in sympathetic cultures has a distinctive
      "dying-back" morphology. Remarkably, this occurs even at concentrations below
      that required to induce neurite outgrowth in PC12 cells. Thus, lactacystin
      opposes rather than potentiates the effect of NGF on sympathetic neurite
      outgrowth and the role of the ubiquitin proteasome pathway in growth and long
      term maintenance of axons and dendrites differs from that in neuritogenesis in
      neuronal-like cell lines. Retrograde degeneration caused by blocking of the
      ubiquitin proteasome pathway may mimic some aspects of gracile axonal dystrophy,
      a dying-back axonopathy in mice caused by ubiquitin hydrolase (Uch-l1)
      deficiency, and may be relevant to human neurodegenerative diseases involving
      ubiquitination or proteasome abnormalities.

PMID- 14648597
TI  - Elevation of mitochondrial glutathione by gamma-glutamylcysteine ethyl ester
      protects mitochondria against peroxynitrite-induced oxidative stress.
AB  - Mitochondria under oxidative stress are thought to play a key role in various
      neurodegenerative disorders by directing neurons to cell death. Protection by
      antioxidants against oxidative stress to mitochondria may prove to be beneficial
      in delaying onset or progression of these diseases. We have investigated the
      ability of gamma-glutamylcysteine ethyl ester (GCEE) to upregulate mitochondrial
      glutathione (GSH) in vivo or in vitro and protect against subsequent in vitro
      peroxynitrite (ONOO-) damage. Mitochondria pretreated in vitro with GCEE were
      protected against oxidative damage induced by peroxynitrite, as assessed by
      mitochondrial swelling, changes in mitochondrial membrane potential, 3
      nitrotyrosine formation, protein carbonyl formation, and cytochrome c release.
      Loss of mitochondrial function in neuronal cell cultures by the oxidants
      2,2,'Azobis(2-amidino-propane)dihydrochloride (AAPH) and ONOO- was ameliorated by
      treatment with GCEE. In vivo studies showed that mitochondria isolated from
      animals injected intraperitoneally with GCEE were protected partially against
      oxidative modifications induced by ONOO-. Taken together, these results suggest
      that GCEE may be effective in increasing mitochondrial GSH and may be prove to
      have therapeutic relevance in neurodegenerative disorders associated with
      oxidative stress and mitochondrial dysfunction.

PMID- 14648598
TI  - Alterations in primary afferent input to substantia gelatinosa of adult rat
      spinal cord after neonatal capsaicin treatment.
AB  - Primary afferent fibers are divided into three main subgroups: Abeta-, Adelta-,
      and C-fibers. Morphological studies have demonstrated that neonatal capsaicin
      treatment (NCT) depletes C-fiber inputs in the spinal dorsal horn; the
      electrophysiological features of the NCT-induced changes, however, remain
      unclear. This issue was addressed by performing whole-cell voltage-clamp
      recordings from substantia gelatinosa (SG) neurons in dorsal root-attached spinal
      cord slices. When estimated from excitatory postsynaptic currents (EPSCs) evoked
      by stimulating primary afferent fibers, 24 (49%) of 49 neurons examined exhibited
      C-fiber EPSCs that were either monosynaptic (n = 15) or polysynaptic (n = 9) in
      origin; only two of the neurons had Abeta-fiber responses. In NCT rats, however,
      SG neurons exhibiting C-fiber-mediated EPSCs decreased to 7% (3 of 41 neurons
      tested), whereas Abeta-fiber EPSCs were observed in 21 (51%) of the neurons, and
      14 (67%) of them exhibited monosynaptic ones. There was no change in the cell
      proportion having Adelta-fiber innervation after NCT. Our electrophysiological
      data suggest that NCT diminishes primary afferent C-fiber inputs while enhancing
      Abeta-fiber direct innervation in the SG in adulthood.

PMID- 14648599
TI  - Quinacrine blocks PrP (106-126)-formed channels.
AB  - We investigated the action of the acridine derivative, quinacrine (QC), which has
      been shown to act as a noncompetitive channel inhibitor. The main effects of QC
      are voltage- and concentration-dependent changes in the kinetics of the prion
      protein fragment (PrP[106-126])-formed cation channels. The current-voltage
      relationships show that the maximal current (I) was not affected whereas the
      physiologically important mean current (I') was reduced as a result of changes in
      channel kinetics. These findings suggest that QC acts on the open state of the
      channels. The half-inhibitory concentration (IC50) for the dose-dependent effects
      of [QC]cis on the kinetic parameters of the PrP(106-126)-formed cation channel
      shows a reduction in the ratios Po(QC)/Po, Fo(QC)/Fo, and To(QC)/To, whereas
      Tc(QC)/Tc increases. Of these ratios, Po(QC)/Po was more sensitive than the
      others. The corresponding IC50 for these ratios were 51, 94, 86, and 250 microM
      QC, respectively. The QC-induced changes in the kinetic parameters were more
      apparent at positive voltages. IC50 values for Po were 95, 75, and 51 microM at
      +20, +80, and +140 mV, respectively. The fact that QC induced changes in the
      kinetics of this channel, although the conductance of the channel remained
      unchanged, indicates that QC may bind at the mouth of the channel via a mechanism
      known as fast channel block. The QC-induced changes in the kinetic parameters of
      this channel suggest that they are pathophysiologically significant because these
      channels could be the mechanisms by which amyloids induce membrane damage in
      vivo.

PMID- 14648600
TI  - Atypical antipsychotics attenuate neurotoxicity of beta-amyloid(25-35) by
      modulating Bax and Bcl-X(l/s) expression and localization.
AB  - We have demonstrated recently that atypical antipsychotics possess
      neuroprotective actions in H2O2-mediated and serum-withdrawal models of cell
      death. In the present study, we compared the ability of atypical and typical
      antipsychotics to protect against an insult mediated by Abeta(25-35), an
      apoptogenic fragment of the Alzheimer's disease-related beta-amyloid (Abeta)
      peptide. Treatment of PC12 cell cultures with Abeta(25-35) did not significantly
      alter total cellular expression levels of Bax, a proapoptotic Bcl-2 family
      member, or levels of Bcl-XL, an antiapoptotic analogue. Treatment with Abeta(25
      35), however, did result in mitochondrial translocation of Bax, which effectively
      increased the mitochondrial ratio of Bax to Bcl-X(L). This relative increase in
      proapoptotic molecules was reduced by pretreatment with atypical (quetiapine and
      olanzapine) and typical (haloperidol) antipsychotics. We also observed a
      selective increase in proapoptotic Bcl-XS immunodetection in haloperidol-treated
      cells, which was evident particularly in the mitochondrial compartment. This
      increase in proapoptotic molecules may account for the lower neuroprotective
      potential of haloperidol, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium (MTT) reduction assay. The disparate neuroprotective effects
      of atypical and typical antipsychotics/neuroleptics may be due to their
      respective abilities to regulate pro- and anti-apoptotic protein translocation
      and expression.

PMID- 14648601
TI  - Iridoids from Scrophularia buergeriana attenuate glutamate-induced neurotoxicity
      in rat cortical cultures.
AB  - In previous work, we isolated 7 neuroprotective iridoid glycosides from the 90%
      MeOH fraction of Scrophularia buergeriana (Scrophulariaceae). We therefore
      investigated the mode of action of 8-O-E-p-methoxycinnamoyl-harpagide (8-MCA
      Harp), the most potent neuroprotective iridoid, and its aglycone, harpagide
      (Harp) using primary cultures of rat cortical cells in vitro. 8-MCA-Harp only
      revealed its neuroprotective activity in a pretreatment paradigm; this iridoid
      had more selectivity in protecting neurons against N-methyl-D-aspartate (NMDA)
      induced neurotoxicity as opposed to that induced by kainic acid (KA). On the
      other hand, Harp exerted significant neuroprotective activity when it was
      administered either before or after glutamate insult and protected cultured
      neuronal cells from neurotoxicity induced by NMDA or KA. Furthermore, Harp
      significantly prevented the decrease of glutathione, an antioxidative compound in
      the brain, in our cultures. Finally, 8-MCA-Harp and Harp could successfully
      reduce the overproduction of nitric oxide and the level of cellular peroxide in
      cultured neurons. Collectively, these results suggested that Harp and 8-MCA-Harp
      protected primary cultured neurons against glutamate-induced oxidative stress
      primarily by acting on the antioxidative defense system and on glutamatergic
      receptors, respectively.

PMID- 14648602
TI  - Glutamate uptake inhibitor L-trans-pyrrolidine 2,4-dicarboxylate becomes
      neurotoxic in the presence of subthreshold concentrations of mitochondrial toxin
      3-nitropropionate: involvement of mitochondrial reducing activity and ATP
      production.
AB  - An increased concentration of extracellular glutamate is associated with neuronal
      damage induced by cerebral ischemia. We have demonstrated previously that
      exposure of cultured cerebellar granule neurons to L-trans-pyrrolidine-2,4
      dicarboxylate (PDC), a glutamate uptake inhibitor, increases extracellular
      glutamate levels but does not induce neuronal damage. Coincubation of PDC,
      however, with a subthreshold concentration of the mitochondrial toxin, 3
      nitropropionic acid (3-NP), results in severe damage to these neurons. We have
      investigated the time course of changes in mitochondrial reducing capacity and
      ATP levels in cerebellar granule cells after simultaneous exposure to 3-NP and
      PDC, and its relation to cell viability and nuclear condensation. Although
      individually, 3-NP and PDC treatments are not harmful to neurons, the
      simultaneous exposure to both compounds results in a progressive decline in
      mitochondrial reducing capacity during the first 4 hr, and a rapid decrease in
      ATP levels. At 4 hr, cells lose plasma membrane integrity and show condensed
      nuclei. In the presence of the energy substrates pyruvate and acetoacetate, the N
      methyl-D-apartate (NMDA) receptor antagonist, MK-801, and the spin trapper alpha
      phenyl-N-tert-butylnitrone (PBN), the decline in mitochondrial activity and ATP
      levels is prevented, the number of condensed nuclei is reduced, and plasma
      membrane integrity is preserved. In contrast, the broad-spectrum caspase
      inhibitor Z-Asp-DCB (Z-Asp-CH2-DCB) prevents nuclear condensation but has no
      effect on mitochondrial reducing capacity or cell survival. Our results show that
      glutamate uptake impairment rapidly induces neuronal death during inhibition of
      succinate dehydrogenase by a mechanism involving mitochondrial dysfunction that,
      if not prevented, leads to cell death.

PMID- 14648603
TI  - Differences in basal levels of CREB and NPY in nucleus accumbens regions between
      C57BL/6 and DBA/2 mice differing in inborn alcohol drinking behavior.
AB  - An increasing body of evidence suggests that genetic factors play a role in
      alcohol drinking behaviors. C57BL/6J (C57) mice innately consume larger amounts
      of alcohol compared to that consumed by DBA/2J (DBA) mice. Furthermore,
      alterations in cAMP-responsive element binding (CREB) protein function in the
      brain have been implicated in alcohol drinking behaviors. The present
      investigation examined innate expression and phosphorylation of CREB in various
      brain structures of C57 and DBA mice. It was found that CREB expression and
      phosphorylation was lower, specifically in the shell structure of the nucleus
      accumbens, in C57 mice compared to that in DBA mice. CREB expression and
      phosphorylation were similar in other brain regions such as the nucleus accumbens
      core and the cortical, amygdaloid, hippocampal, and striatal structures of C57
      and DBA mice. The expression of a cAMP-inducible gene, neuropeptide Y (NPY), was
      also investigated in the nucleus accumbens region of C57 and DBA mice. It was
      found that in C57 mice, NPY protein levels were lower in the shell but not in the
      core structure of the nucleus accumbens compared to that in DBA mice. It was also
      found that C57 mice are not innately anxious, but they consume larger amounts of
      alcohol than do DBA mice. Because the shell structure of the nucleus accumbens
      has been implicated in reward mechanisms of alcohol, it is possible that lower
      CREB function in this brain structure may be in part associated with the
      excessive alcohol drinking behavior of C57 mice.

PMID- 14648604
TI  - A sensitive and rapid liquid chromatography tandem mass spectrometry method for
      quantitative determination of 7-ethyl-10-hydroxycamptothecin (SN-38) in human
      plasma containing liposome-based SN-38 (LE-SN38).
AB  - 7-Ethyl-10-hydroxycamptothecin (SN-38) is an active metabolite of Irinotecan (CPT
      11), an anticancer pro-drug. To support clinical pharmacokinetic studies for
      liposome based formulation of SN-38 (LE-SN38) in cancer patients, a rapid, simple
      and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method
      has been developed and validated for the quantification of total SN-38 in human
      plasma. Sample preparation was carried out by one-step protein precipitation
      using cold acetonitrile with 0.5% acetic acid (v/v). Camptothecin was used as an
      internal standard (IS). Chromatographic separation of SN-38 and IS was achieved
      using a Synergi Hydro-RP column (C(18), 50 x 2 mm, 4 micro m), with a gradient
      elution of acetonitrile and 0.1% acetic acid. After ionization in electrospray
      source (positive ions), the acquisition was performed in the multiple reactions
      monitoring mode. Quantitation was accomplished using the precursor-->product ion
      combinations of m/z 393.1-->349.2 for SN-38 and 349.1-->305.1 for IS. The
      quantification limit of 0.05 ng/mL was achieved by using much lower volume (0.2
      mL) of plasma and in the presence of LE-SN38. The method was validated over the
      concentration range of 0.05-400 ng/mL. Accuracy was within +/-12% of nominal at
      all concentration levels. Inter-day and intra-day precisions expressed as
      percentage coefficient of variation (%CVs) for quality control (QC) samples were
      less than 14 and 5%, respectively.

PMID- 14648605
TI  - A simple and simultaneous determination of acyclovir and ganciclovir in human
      plasma by high-performance liquid chromatography.
AB  - A simple high-performance liquid chromatographic method was developed for the
      simultaneous determination of the therapeutic levels of acyclovir and ganciclovir
      in human plasma. After precipitation of plasma proteins with 6% perchloric acid,
      acyclovir and ganciclovir were simultaneously determined by reversed-phase
      chromatography with spectophotometric detection at 254 nm. The peak heights for
      acyclovir and ganciclovir were linearly related to their concentrations ranging
      from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and
      99.26-103.07% for ganciclovir. The intra- and inter-day relative standard
      deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424%
      for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL
      determined as the signal-to-noise ratio of 3. The present method is applicable to
      therapeutic monitoring during antiviral medication.

PMID- 14648606
TI  - Determination of paeonol in rat plasma by high-performance liquid chromatography
      and its application to pharmacokinetic studies following oral administration of
      Moutan cortex decoction.
AB  - Quantification of paeonol, the principal bioactive component of Moutan cortex, in
      rat plasma following oral administration of Moutan cortex decoction was achieved
      by using a simple and sensitive high-performance liquid chromatographic method.
      The calibration curves for paeonol were linear in both the low (25-200 ng/mL) and
      the high concentration range (200-4000 ng/mL) with r(2) values of 0.9928 and
      0.9993, respectively. The coefficients of variation of intra- and inter-day
      assays were 14.36, 6.52, 1.76, 1.25, 5.36, 3.30 and 1.42% and 12.70, 1.19, 2.98,
      1.91, 1.75, 1.78 and 0.96% at concentrations of 25, 50, 100, 200, 500, 1000 and
      2000 ng/mL, respectively. The recoveries of paeonol from rat plasma were found to
      be 101.9, 104.5, 105.4 and 101.2% for concentrations of 50, 500, 1000 and 2000
      ng/mL, respectively. The paeonol plasma concentrations were fitted to two
      compartment model with fi rst order absorption. The mean terminal half-lives
      (t(1/2)) of paeonol was 80.9 min.

PMID- 14648607
TI  - A sensitive and selective determination method of histamine by HPLC with
      intramolecular excimer-forming derivatization and fluorescence detection.
AB  - A highly sensitive, selective and simple method is described for the
      determination of histamine by high-performance liquid chromatography (HPLC) with
      fluorescence detection. The method is based on an intramolecular excimer-forming
      fluorescence derivatization of histamine with 4-(1-pyrene)butyric acid N
      hydroxysuccinimide ester (PSE), followed by reversed-phase HPLC. Histamine,
      having two amino moieties in a molecule, was converted to the dipyrene-labeled
      derivative by reaction with PSE. The derivative afforded intramolecular excimer
      fluorescence (450-540 nm), which can clearly be discriminated from the monomer
      fluorescence (370-420 nm) emitted from PSE. Typically, a 10 micro L sample
      solution was mixed with 100 micro L of derivatization reagent solution, which was
      a mixture of 0.5 mm PSE in acetonitrile and 0.5 mm potassium carbonate in water
      (8:2, v/v). The derivatization was carried out at 100 degrees C for 90 min. The
      PSE derivative of histamine could be separated by reversed-phase ODS column with
      isocratic elution using acetonitrile:water (82:18, v/v) containing 0.03%
      triethylamine. The detection limit (singnal-to-noise ratio = 3) of histamine was
      0.5 fmol for a 30 micro L injection. The method was successfully applied to the
      determination of histamine in human urine, and had enough selectivity and
      sensitivity for urinary histamine quantification.

PMID- 14648608
TI  - Simultaneous quantitative analysis of ketanserin and ketanserinol in plasma by RP
      HPLC with fluorescence detection.
AB  - A sensitive and selective high-performance liquid chromatographic assay for the
      quantification of ketanserin and ketanserinol in human plasma was developed and
      validated. The procedure involves extraction of ketanserin and ketanserinol from
      plasma using an Extrelut NT-1 solid-phase extraction column. The chromatograph
      was equipped with a Hypersil BDS column (100 x 4.5 mm, 3 micro m particle size).
      Separation was performed with a mixture of acetate buffer 0.01 M, pH 4.9-methanol
      acetonitrile (52:40:8, v/v/v). Detection was performed with fluorescence
      detection (lambda(ex) = 332 nm and lambda(em) = 410 nm). Calibration curves were
      linear (r(2) = 0.999) in the range 0-400 ng/mL for both ketanserin and
      ketanserinol. The repeatability coefficient for ketanserin and ketanserinol was
      3.1 and 3.0%, respectively. The reproducibility coefficient for ketanserin and
      ketanserinol was 10.5 and 9.1%, respectively. The limit of quantification for
      both ketanserin and ketanserinol was 2.0 ng/mL. The mean recovery yield for both
      ketanserin and ketanserinol was 60%. In an 8 h work day approximately 60 samples,
      including calibration and reference standards, could be processed.

PMID- 14648609
TI  - HPLC determination of diltiazem in human plasma and its application to
      pharmacokinetics in humans.
AB  - A simple and sensitive reversed-phase high performance liquid chromatographic
      method (HPLC) has been developed and validated for the routine analysis of
      diltiazem in human plasma and the study of the pharmacokinetics of the drug in
      the human body. Diltiazem and diazepa (internal standard) were extracted with a
      mixed organic solution of hexane, chloroform and isopropanol (60:40:5, v/v/v),
      and then HPLC separation of the drugs was performed on an Spherisorb C(18) column
      and detected by ultraviolet absorbance at 239 nm. The use of methanol-water
      solution (containing 2.8 mm triethylamine, 80:20, v/v) as the mobile phase at a
      fl ow-rate of 1.2 mL/min enables the baseline separation of the drugs free from
      interferences with isocratic elution. The method was linear in the clinical range
      0-300 ng/mL and the lower limit of detection of diltiazem in plasma was 3 ng/mL.
      The range of percentage of relative standard deviation (%RSD) was from 3.5 to
      6.8% for within-day analyses and from 6.2 to 8.4% for between-day analyses,
      respectively. The extraction recoveries of diltiazem from spiked human plasma (n
      = 5) at three concentrations were 91.4-104.0%. The method has been used to
      determine diltiazem in human plasma samples from eight volunteers who had taken
      diltiazem hydrochloride slow release tables and the data obtained was fitted with
      a program on computer to study the pharmacokinetics. The results showed that the
      peak level in plasma approximately averaged 118.5 +/- 14.3 ng/mL at 3.1 +/- 0.4
      h, and the areas under the drug concentration curves (AUC) was 793.1 +/- 83.1
      ng.h/mL.

PMID- 14648610
TI  - Characterization of porphyrins of rat Harderian gland by thin layer
      chromatography and mass spectrometry: no evidence for a tricarboxylic acid
      porphyrin.
AB  - Reversed-phase TLC systems using ion-pairing reagents are described for the
      separation without prior derivatization of the porphyrins of rat Harderian gland.
      Porphyrins with R(f) values greater than protoporphyrin but smaller than
      coproporphyrin, representing harderoporphyrin, were labile to 1 m NaOH, which
      converted them to protoporphyrin, inconsistent with the established literature
      that harderoporphyrin is a tricarboxylic acid porphyrin. It was confirmed by
      HPLC/electrospray ionization MS that this 'harderoporphyrin' fraction consists of
      the recently characterized glycoconjugate, protoporphyrin-1-O-acyl beta-xyloside,
      with trace amounts of protoporphyrin-1-O-acyl beta-glucoside.

PMID- 14648611
TI  - Biopartitioning micellar chromatography to predict skin permeability.
AB  - Dermal absorption of chemicals is an area of increasing interest to the
      pharmaceutical and cosmetic industries, as well as in dermal exposure and risk
      assessment processes. In this paper the capability of biopartitioning micellar
      chromatography (BMC) as an in vitro technique to describe compound percutaneous
      absorption is evaluated. A multivariate study (principal component analysis,
      partial least squares) is performed in order to evaluate the importance of some
      physicochemical variables on the skin permeability constant values. From these
      results, a quantitative retention-activity relationship model for predicting the
      skin permeability constants that uses the BMC retention data and melting point as
      descriptor variables was obtained from a heterogeneous set of 43 compounds. The
      main advantage of the proposed methodology is that it allows the obtention of
      permeability constants of ionic compound and it can be very useful to predict the
      effect of pH of vehicle on the skin permeability of xenobiotics.

PMID- 14648612
TI  - Influence of nonionic surfactants on the chromatographic behaviour of proteins in
      hydrophobic interaction chromatography.
AB  - The chromatographic characteristics of proteins in the presence of additives of
      nonionic surfactants Brij-35 and Tween-80 in the conditions of descending
      gradient of ammonium sulfate and phenyl-coated polymeric stationary phase were
      investigated. It was revealed that retention factors of proteins may be regulated
      by use of mentioned additives. The improvement of resolution is achieved for some
      hardly separated pairs of proteins, viz. albumin egg/albumin bovine,
      aldolase/tripsin. A reversion of the elution order is observed for
      tripsin/chymotrypsinogen A.

PMID- 14648613
TI  - HPLC determination of ferulic acid in rat plasma after oral administration of
      Rhizoma Chuanxiong and its compound preparation.
AB  - An HPLC method is described for determination of ferulic acid in rat plasma. The
      concentration of ferulic acid in rat plasma was determined after deproteinization
      with acetonitrile using sulfamethoxazole as internal standard. Chromatographic
      separations were performed on a C(18) stationary phase with a mobile phase
      composed of acetonitrile-water (16:84, v/v) with 1% glacial acetic acid. The UV
      detection wavelength was set at 320 nm. The method was successfully applied to
      the determination of pharmacokinetic parameters in rat plasma after oral
      administration of Rhizoma Chuanxiong and and its compound preparation Suanzaoren
      decoctions. The calibration curve was linear over the range 0.0510-4.08 micro
      g/mL in rat plasma. Within-day and between-day precisions were less than 4.5%
      RSD. Mean recovery was determined as 96.9%. The limit of quantitation was 0.0510
      micro g/mL. The pharmacokinetic parameters of the two preparations were different
      significantly (p < 0.05), which may attribute to the effects of other ingredients
      present in Suanzaoren decoction.

PMID- 14648614
TI  - TGSA-Flex: Extending the capabilities of the Topo-Geometrical Superposition
      Algorithm to handle flexible molecules.
AB  - In this work, an extension of the already studied Topo-Geometrical Superposition
      Approach (TGSA) is presented. TGSA, a general-purpose, fast, automatic, and user
      intuitive three-dimensional molecular alignment procedure, was originally
      designed to superpose rigid molecules simply based on atomic numbers, molecular
      coordinates, and connectivity. The algorithm is further developed to enable
      handling rotations around single bonds; in this way, common structural features,
      which were not properly aligned due to conformational causes, can be brought
      together, thus improving the molecular similarity picture of the final alignment.
      The present procedure, implemented in Fortran 90 and named TGSA-Flex, is deeply
      detailed and tested over four molecular sets: amino acids, nordihydroguaiaretic
      acid (NDGA) derivatives, HIV-1 protease inhibitors, and 1-[2
      hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. TGSA-Flex
      performance is evaluated by means of computational time, number of superposed
      atoms (also comparing it with respect to the rigid approach), and index of fit
      between the compared structures.

PMID- 14648615
TI  - Conformation-dependent intermolecular interaction energies of the triphosphate
      anion with divalent metal cations. Application to the ATP-binding site of a
      binuclear bacterial enzyme. A parallel quantum chemical and polarizable molecular
      mechanics investigation.
AB  - We have explored the conformation-dependent interaction energy of the
      triphosphate moiety, a key constituent of ATP and GTP, with a closed-shell
      divalent cation, Zn2+, used as a probe. This was done using the SIBFA polarizable
      molecular mechanics procedure. We have resorted to a previously developed
      approach in which triphosphate is built out from its elementary constitutive
      fragments, and the intramolecular, interfragment, interaction energies are
      computed simultaneously with their intermolecular interactions with the divalent
      cation. This approach has enabled reproduction of the values of the
      intermolecular interaction energies from ab initio quantum-chemistry with
      relative errors <3%. It was extended to the complex of a nonhydrolyzable analog
      of ATP with the active site of a bacterial enzyme having two Mg2+ cations as
      cofactors. We obtained following energy-minimization a very close overlap of the
      ATP analog over its position from X-ray crystallography. For models of the ATP
      analog-enzyme complex encompassing up to 169 atoms, the values of the SIBFA
      interaction energies were found to match their DFT counterparts with relative
      errors of <2%.

PMID- 14648616
TI  - Computational study of conformational preferences of thioamide-containing
      azaglycine peptides.
AB  - The effect of thioamide substitution on the conformational stability of an
      azaglycine-containing peptide, For-AzaGly-NH2 (1), was investigated for the sake
      of finding possible applications by using ab initio and DFT methods. As model
      compounds, For-[psiCSNH]-AzaGly-NH2 (2), For-AzaGly-[psiCSNH]-NH2 (3), and For
      [psiCSNH]-AzaGly-[psiCSNH]-NH2 (4) were used. Two-dimensional phi-psi potential
      energy surfaces (PESs) for 2-4 were calculated at the B3LYP/6-31G*//HF/6-31G*
      level in gas (epsilon = 1.0) and in water (epsilon = 78.4) by applying the
      isodensity polarizable continuum model (IPCM) method. On the basis of these PESs,
      the minimum energy conformations for 2-4 were characterized at the B3LYP level
      with 6-31G*, 6-311G**, and 6-31+G** basis sets. The remarkable structural effect
      of thioamide substitution for 2-4 is that beta-strand structure is observed as a
      global or local minimum. The minima of 2-4 are also compared with those for
      glycine and thioamide-containing glycine peptides. Our theoretical results
      demonstrate that compounds 2-4 would be used to design controllable secondary
      structures.

PMID- 14648617
TI  - Theoretical study on the excited states of psoralen compounds bonded to a thymine
      residue.
AB  - Time-dependent density functional theory calculations have been performed for the
      excited states of psoralen, 5-methoxypsoralen, and 8-methoxypsoralen in systems
      and furan and pyrone monoadducts bonded to a thymine residue. The theoretical
      assignments to ultraviolet (UV) absorption spectra of isolated systems have been
      performed. The present calculations have clarified that the excitation energies
      of the first singlet excited (S1) state of monoadducts are blue-shifted compared
      with the isolated systems. It is shown that, in particular, the S1 excitation
      energy of the pyrone monoadduct is significantly blue-shifted and, therefore, the
      pyrone monoadduct is not excited by UV-A light (300-400 nm), which is used in the
      photochemotherapy.

PMID- 14648618
TI  - Voronoi deformation density (VDD) charges: Assessment of the Mulliken, Bader,
      Hirshfeld, Weinhold, and VDD methods for charge analysis.
AB  - We present the Voronoi Deformation Density (VDD) method for computing atomic
      charges. The VDD method does not explicitly use the basis functions but
      calculates the amount of electronic density that flows to or from a certain atom
      due to bond formation by spatial integration of the deformation density over the
      atomic Voronoi cell. We compare our method to the well-known Mulliken, Hirshfeld,
      Bader, and Weinhold [Natural Population Analysis (NPA)] charges for a variety of
      biological, organic, and inorganic molecules. The Mulliken charges are (again)
      shown to be useless due to heavy basis set dependency, and the Bader charges (and
      often also the NPA charges) are not realistic, yielding too extreme values that
      suggest much ionic character even in the case of covalent bonds. The Hirshfeld
      and VDD charges, which prove to be numerically very similar, are to be
      recommended because they yield chemically meaningful charges. We stress the need
      to use spatial integration over an atomic domain to get rid of basis set
      dependency, and the need to integrate the deformation density in order to obtain
      a realistic picture of the charge rearrangement upon bonding. An asset of the VDD
      charges is the transparency of the approach owing to the simple geometric
      partitioning of space. The deformation density based charges prove to conform to
      chemical experience.

PMID- 14648619
TI  - Characterization of dynamics and reactivities of solvated ions by ab initio
      simulations.
AB  - Based on a systematic investigation of trajectories of ab initio quantum
      mechanical/molecular mechanical simulations of numerous cations in water a
      standardized procedure for the evaluation of mean ligand residence times is
      proposed. For the characterization of reactivity and structure-breaking/structure
      forming properties of the ions a measure is derived from the mean residence times
      calculated with different time limits. It is shown that ab initio simulations can
      provide much insight into ultrafast dynamics that are presently not easily
      accessible by experiment.

PMID- 14648620
TI  - A dual-level ab initio and hybrid density functional theory dynamics study on the
      unimolecular decomposition reaction C2H5O-->CH2O + CH3.
AB  - We present a direct ab initio and hybrid density functional theory dynamics study
      of the thermal rate constants of the unimolecular decomposition reaction of C2H5O
      ->CH2O + CH3 at a high-pressure limit. MPW1K/6-31+G(d,p), MP2/6-31+G(d,p), and
      MP2(full)/6-31G(d) methods were employed to optimize the geometries of all
      stationary points and to calculate the minimum energy path (MEP). The energies of
      all the stationary points were refined at a series of multicoefficient and
      multilevel methods. Among all methods, the QCISD(T)/aug-cc-pVTZ energies are in
      good agreement with the available experimental data. The rate constants were
      evaluated based on the energetics from the QCISD(T)/aug-cc-pVTZ//MPW1K/6
      31+G(d,p) level of theory using both microcanonical variational transition state
      theory (microVT) and RRKM theory with the Eckart tunneling correction in the
      temperature range of 300-2500 K. The calculated rate constants at the
      QCISD(T)/aug-cc-pVTZ/MPW1K/6-31+G(d,p) level of theory are in good consistent
      with experimental data. The fitted three-parameter Arrhenius expression from the
      microVT/Eckart rate constants in the temperature range 200-2500 K is k = 2.52 x
      10(12)T(0.41)e(-8894.0/T) s(-1). The falloff curves of pressure-dependent rate
      constants are performed using master-equation method within the temperature range
      of 391-471 K. The calculated results are in good agreement with the available
      experimental data.

PMID- 14648621
TI  - Theoretical study of ribonucleotide reductase mechanism-based inhibition by 2'
      azido-2'-deoxyribonucleoside 5'-diphosphates.
AB  - 2'-azido-2'-deoxyribonucleoside 5'-diphosphates are mechanism-based inhibitors of
      Ribonucleotide Reductase. Considerable effort has been made to elucidate their
      mechanism of inhibition, which is still controversial and not fully understood.
      Previous studies have detected the formation of a radical intermediate when the
      inhibitors interact with the enzyme, and several authors have proposed possible
      structures for this radical. We have conducted a theoretical study of the
      possible reactions involved, which allowed us to identify the structure of the
      new radical among the several proposals. A new reactional path is also proposed
      that is the most kinetically favored to yield this radical and ultimately
      inactivate the enzyme. The energetic involved in this mechanism, both for radical
      formation and radical decay, as well as the calculated Hyperfine Coupling
      Constants for the radical intermediate, are in agreement with the correspondent
      experimental values. This mechanistic alternative is fully coherent with
      remaining experimental data.

PMID- 14648622
TI  - Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein
      complex Ras-Raf.
AB  - Estimating protein-protein interaction energies is a very challenging task for
      current simulation protocols. Here, absolute binding free energies are reported
      for the complex H-Ras/C-Raf1 using the MM-PB(GB)SA approach, testing the internal
      consistency and model dependence of the results. Averaging gas-phase energies
      (MM), solvation free energies as determined by Generalized Born models (GB/SA),
      and entropic contributions calculated by normal mode analysis for snapshots
      obtained from 10 ns explicit-solvent molecular dynamics in general results in an
      overestimation of the binding affinity when a solvent-accessible surface area
      dependent model is used to estimate the nonpolar solvation contribution. Applying
      the sum of a cavity solvation free energy and explicitly modeled solute-solvent
      van der Waals interaction energies instead provides less negative estimates for
      the nonpolar solvation contribution. When the polar contribution to the solvation
      free energy is determined by solving the Poisson-Boltzmann equation (PB) instead,
      the calculated binding affinity strongly depends on the atomic radii set chosen.
      For three GB models investigated, different absolute deviations from PB energies
      were found for the unbound proteins and the complex. As an alternative to normal
      mode calculations, quasiharmonic analyses have been performed to estimate
      entropic contributions due to changes of solute flexibility upon binding.
      However, such entropy estimates do not converge after 10 ns of simulation time,
      indicating that sampling issues may limit the applicability of this approach.
      Finally, binding free energies estimated from snapshots of the unbound proteins
      extracted from the complex trajectory result in an underestimate of binding
      affinity. This points to the need to exercise caution in applying the
      computationally cheaper "one-trajectory-alternative" to systems where there may
      be significant changes in flexibility and structure due to binding. The best
      estimate for the binding free energy of Ras-Raf obtained in this study of -8.3
      kcal mol(-1) is in good agreement with the experimental result of -9.6 kcal mol(
      1), however, further probing the transferability of the applied protocol that led
      to this result is necessary.

PMID- 14648623
TI  - Direct dynamic study on the hydrogen abstraction reaction CH3CN + OH-->CH2CN +
      H2O.
AB  - The reaction of acetonitrile with hydroxyl has been studied using the direct ab
      initio dynamics methods. The geometries, vibrational frequencies of the
      stationary points, as well as the minimum energy paths were computed at the
      BHandHLYP and MP2 levels of theory with the 6-311G(d, p) basis set. The energies
      were further refined at the PMP4/6-311+G(2df, 2pd) and QCISD(T)/6-311+G(2df, 2pd)
      levels of theory based on the structures optimized at BHandHLYP/6-311G(d, p) and
      MP2/6-311G(d, p) levels of theory. The Polyrate 8.2 program was employed to
      predict the thermal rate constants using the canonical variational transition
      state theory incorporating a small-curvature tunneling correction. The computed
      rate constants are in good agreement with the available experimental data.

PMID- 14648624
TI  - Density functional investigation of reaction of borohydride cation BH2+ with
      propylene.
AB  - The reactions of BH2+ with propylene (CH2=CHCH3) to form both the adducts BC3H8+
      and the H2-elimination products BC3H6+ + H2 have been investigated at the density
      functional B3LYP/6-311G(d,p) level of theory. It is shown that the electrophilic
      attacks of BH2+ towards two olefinic carbons of H2C=CHCH3 and two subsequent 1,3
      H-shifts may form four low-lying BC3H8+ isomers (with the relative energies in
      parentheses in kcal/mol): 1 BH2+.CH2CHCH3 (0.0), 1' BH2+.CH3CHCH2 (6.3), 3
      BHCH2CH2CH3+ (4.3), and 4 BHCH(CH3)2+ (5.0), respectively. On the other hand,
      further H2-eliminations may also occur easily between B-C bonds of isomers 1 and
      1' and between C-C bonds of isomers 3 and 4 to form two dissociation products
      (P1) HBCHCHCH3+ + H2 and (P2) HBC(CH3)CH2+ + H2, with H2-elimination from isomer
      1 to be energetically most favorable. According to our calculated mechanism, the
      collisional stabilization processes of low-lying isomers 1, 1', 3, and 4 may
      compete extensively with their H2-eliminations processes for the title reaction,
      leading mainly to some linear carborane cations. This study may be helpful for
      understanding the stereochemical aspects of borohydride cations towards
      alkylenes.

PMID- 14648625
TI  - Performance comparison of generalized born and Poisson methods in the calculation
      of electrostatic solvation energies for protein structures.
AB  - This study compares generalized Born (GB) and Poisson (PB) methods for
      calculating electrostatic solvation energies of proteins. A large set of GB and
      PB implementations from our own laboratories as well as others is applied to a
      series of protein structure test sets for evaluating the performance of these
      methods. The test sets cover a significant range of native protein structures of
      varying size, fold topology, and amino acid composition as well as nonnative
      extended and misfolded structures that may be found during structure prediction
      and folding/unfolding studies. We find that the methods tested here span a wide
      range from highly accurate and computationally demanding PB-based methods to
      somewhat less accurate but more affordable GB-based approaches and a few fast,
      approximate PB solvers. Compared with PB solvation energies, the latest, most
      accurate GB implementations were found to achieve errors of 1% for relative
      solvation energies between different proteins and 0.4% between different
      conformations of the same protein. This compares to accurate PB solvers that
      produce results with deviations of less than 0.25% between each other for both
      native and nonnative structures. The performance of the best GB methods is
      discussed in more detail for the application for force field-based minimizations
      or molecular dynamics simulations.

PMID- 14648626
TI  - On the flexibility of beta-peptides.
AB  - The full conformational space was explored for an achiral and two chiral beta
      peptide models: namely For-beta-Ala-NH2, For-beta-Abu-NH2, and For-beta-Aib-NH2.
      Stability and conformational properties of all three model systems were computed
      at different levels of theory: RHF/3-21G, B3LYP/6-311++G(d,p)//RHF/3-21G, B3LYP/6
      311++G(d,p), MP2//B3LYP/6-311++G(d,p), CCSD//B3LYP/6-311++G(d,p), and
      CCSD(T)//B3LYP/6-311++G(d,p). In addition, ab initio E = E(phi, micro, psi)
      potential energy hypersurfaces of all three models were determined, and their
      topologies were analyzed to determine the inherent flexibility properties of
      these beta-peptide models. Fewer points were found and assigned than expected on
      the basis of Multidimensional Conformational Analysis (MDCA). Furthermore, it has
      been demonstrated, that the four-dimensional surface, E = E(phi, mu, psi), can be
      reduced into a three-dimensional one: E = E[phi, f(phi), psi]. This reduction of
      dimensionality of freedom of motion suggests that beta-peptides are less flexible
      than one would have thought. This agrees with experimental data published on the
      conformational properties of peptides composed of beta-amino acid residues.

PMID- 14648630
TI  - Physics of amorphous solids.
AB  - The physical state of a dosage form, crystalline versus amorphous, is critical in
      determining its solid-state physical and chemical properties. This minireview
      describes the physics associated with the preparation and storage of amorphous
      solids including a review of the common theories of the glass transition and
      relaxation processes.

PMID- 14648631
TI  - In vitro uptake of a new cholesteryl carborane ester compound by human glioma
      cell lines.
AB  - The cellular uptake and retention of a new cholesteryl carborane ester compound,
      cholesteryl 1,12-dicarba-closo-dodecaboranel-carboxylate (BCH), by two human
      glioma cell lines, glioblastoma multiforme SF-763 and SF-767, was evaluated. BCH,
      which is an extremely hydrophobic compound, was formulated into liposomes and
      incubated with two human glioma tumor cell lines and one human normal neuron cell
      line. The amount of BCH uptake by the cells was measured by high performance
      liquid chromatography. The effects of BCH concentration in the culture medium and
      the incubation time on the cellular uptake of BCH were studied. In addition, BCH
      uptake by tumor cells was examined in the presence and absence of lipoprotein in
      the culture medium. It was found that the amount of BCH taken by the glioma cell
      lines was much more (up to 14 times) than that by the normal neuron cell line.
      The cellular uptake of BCH was related to the amount of BCH in the medium as well
      as the incubation time. The cellular uptake of BCH by SF-763 and SF-767 cells
      after 16 h of incubation was 283.3 +/- 38.9 and 264.0 +/- 36.5 microg boron/g
      cells, respectively. The majority of BCH taken up in tumor cells was retained
      after the subsequent incubation. In the presence of lipoprotein, the cellular
      uptake of BCH by SF-767 tumor cells was about four times as much as that in the
      absence of lipoprotein. In conclusion, the cellular uptake of BCH by glioma cells
      was about 14 times higher than by normal neuron cells. The uptake in glioma cells
      was up to 10 times higher than that required for successful cancer treatment and
      BCH was well retained in the tumor cells. Lipoprotein seemed to have an important
      role in the BCH uptake by glioma cells.

PMID- 14648632
TI  - Mechanistic study of the uptake of wheat germ agglutinin-conjugated PLGA
      nanoparticles by A549 cells.
AB  - The purpose of this study was to evaluate the extent and mechanism of uptake of
      wheat germ agglutinin-conjugated PLGA nanoparticles by A549 cells. PLGA
      nanoparticles of 150 nm were prepared by a solvent diffusion method and
      covalently conjugated to FITC-WGA (fWGA) or FITC-bovine serum albumin (fBSA) by a
      two-step carbodiimide method. Uptake of fWGA-PLGA and fBSA-PLGA nanoparticles by
      confluent A549 cells was quantified by fluorometry. A549 cellular uptake of fWGA
      PLGA nanoparticles at 2 h, 37 degrees C was 5.02-fold that of fBSA-PLGA
      nanoparticles at a loading concentration of 2.65 mg/mL. The difference in uptake
      between the two types of nanoparticles was increased to 7.84-fold at a higher
      loading concentration of 5.3 mg/mL, but was reduced to 2.07-fold by lowering the
      uptake temperature to 4 degrees C. Coincubation with 5 mg/mL of unlabeled WGA
      negated the differential uptake of fWGA-PLGA nanoparticles at 4 degrees C,
      suggesting that the nanoparticles interacted with a specific WGA-binding receptor
      on the cell membrane. Internalization of the fWGA-PLGA nanoparticles by the A549
      cells was confirmed by confocal microscopy. Filipin (1 microg/mL), a known
      inhibitor of caveolae, reduced the 1-h uptake of the nanoparticles by 75%.
      Surface modification of PLGA nanoparticles with WGA significantly enhanced its
      endocytosis by A549 cells by a receptor-mediated, caveola-dependent pathway.

PMID- 14648633
TI  - Moisture-induced surface crystallization of spray-dried amorphous lactose
      particles studied by atomic force microscopy.
AB  - The aim of this study was to show that atomic force microscopy (AFM) can be used
      to obtain mechanistic and kinetic information about the process of moisture
      induced surface crystallization of single particles of amorphous lactose.
      Completely amorphous lactose particles were prepared by spray-drying a solution
      of alpha-lactose monohydrate, and moisture-induced crystallization was monitored
      for a bed of particles by microcalorimetry and for single particles by AFM. From
      the AFM images it was found that crystallization of the surface of single
      particles can be described in terms of a sequence of three events: an initial
      smoothening of the surface, formation of crystalline nanostructures dispersed in
      amorphous material, and growth of these structures to a complete crystalline
      surface. The surface roughness parameter rugosity was used to estimate the
      fraction crystalline surface, and the growth kinetics were found to obey the JMAK
      equation. The fraction crystalline surface at different times could also be
      estimated by determining the growth rate of individual crystals. It was concluded
      that AFM offers a unique means of visualizing the process of moisture-induced
      surface crystallization of amorphous particles and enables mechanistic and
      kinetic information about the process to be extracted.

PMID- 14648634
TI  - Preformulation studies to meet the challenges in the manufacture of betaine solid
      dosage form.
AB  - The objectives were (1). to perform solid-state characterization of anhydrous
      betaine (A) and betaine monohydrate (M), (2). to develop a pressure differential
      scanning calorimetric (DSC) technique for the quantification of M when present as
      a minor component in a mixture with A and, (3). to study the effect of annealing
      of A on the kinetics of A --> M transition. X-ray powder diffractometer (XRD),
      DSC, thermogravimetric analyzer (TGA), and an automated moisture sorption
      apparatus were used to characterize the phases. DSC at an elevated pressure of
      200 psi enabled quantification of M in mixtures of A and M. Humidity-controlled
      TGA allowed study of the kinetics of A --> M transition. Automated moisture
      studies showed that A has a strong tendency to sorb water (at RH >or= 20%, 25
      degrees C) and convert to M. When M was subjected to DSC at ambient pressure, the
      endotherms due to dehydration and vaporization of water overlapped. Pressure DSC
      enabled separation of these two thermal events. In mixtures of A and M, the
      enthalpy of dehydration (deltaH(d)) of M could be used for its quantification. A
      linear relationship was obtained when deltaH(d) was plotted as a function of the
      weight fraction of M in the mixture. The limits of detection and quantification
      of M in A were 0.15% and 1.5% w/w, respectively. The kinetics of water uptake by
      the annealed as well as the unannealed A, could be best described by the Avrami
      Erofeev model (three-dimensional nucleation and growth). The calculated rate
      constant (k) of unannealed A (0.075 +/- 0.002 min(-1)) was significantly higher
      than that of annealed A (0.052 +/- 0.004 min(-1)). DSC at elevated pressure was a
      sensitive technique for quantification of M when present as a mixture with A.
      Annealing of A decelerated the A --> M phase transition reaction, possibly by
      increasing the degree of crystallinity of A.

PMID- 14648635
TI  - Tissue disposition of 2'-O-(2-methoxy) ethyl modified antisense oligonucleotides
      in monkeys.
AB  - This study examined the plasma pharmacokinetics, tissue distribution, and
      metabolism of three second generation antisense oligonucleotides in monkeys.
      Three groups of monkeys were treated with 10 mg/kg of each test compound by a
      single 2-h intravenous infusion. Oligonucleotide concentrations were measured in
      plasma, tissues, and urine using capillary gel electrophoresis (CGE). HPLC-MS was
      used to identify the metabolite(s) of the study compounds. Plasma-concentration
      time profiles after infusion for the two phosphorothioate oligonucleotides were
      mono-exponential, but was bi- exponential for the phosphodiester oligonucleotide.
      Plasma clearance for the phosphodiester oligonucleotide was four- to sevenfold
      higher than the two phosphorothioate oligonucleotides, which was attributed to
      the plasma protein binding and reduced nuclease resistance. 2'-O-(2-methoxy)
      ethyl (MOE) modification at both 3' and 5' ends of a phosphorothioate
      oligonucleotide greatly enhanced the resistance to nucleases in plasma and
      tissue. MOE modification only at the 3' end enhanced the resistance to nucleases
      in plasma, but only moderately enhanced the resistance to nucleases in tissues.
      Urinary excretion was a minor elimination pathway for the phosphorothioate
      oligonucleotide, but was a major elimination pathway for the phosphodiester
      oligonucleotide. The results characterize the relationships between structure and
      disposition and will direct future modifications for therapeutic use.

PMID- 14648636
TI  - Application of a fluorescence sensor for miniscale on-line monitoring of powder
      mixing kinetics.
AB  - A portable system using light-induced fluorescence technology (LIF) was
      development as an analytical tool for on-line monitoring of various manufacturing
      process applications. The LIF system was verified in several laboratory scale
      process applications specifically in noninvasive real-time observations of blend
      kinetics in tumbler blenders. This technology, through careful selection of
      filters for specific formulations, can provide clean and unadulterated raw data
      that shows the actual blend characteristic behavior of powder mixtures such as
      homogeneity end point and blend stability. Consistent blend homogeneity end point
      was demonstrated for all runs with LIF where data were verified by thief sampling
      and UV spectrophotometric assays. A correlation between LIF signal and drug
      powder concentration was established with limits of detection below 0.02% w/w for
      the API, Triamterene.

PMID- 14648637
TI  - A new system for the prediction of drug absorption using a pH-controlled Caco-2
      model: evaluation of pH-dependent soluble drug absorption and pH-related changes
      in absorption.
AB  - One purpose of this study was to develop a new system for the prediction of pH
      dependent soluble drug absorption that takes into account the physiological
      condition of the gastrointestinal tract. Another purpose was to establish several
      models of different gastric acidities: a normal gastric acidity model, a low
      gastric acidity model (a model of achlorhydria), a temporarily elevated gastric
      acidity model (a model of a case in which an acidic drug was coadministered to
      temporarily elevate gastric acidity in the case of low gastric acidity), a weak
      antacid model (a model of a case in which a weak antacid drug, such as an H(2)
      receptor antagonist, was coadministered to temporarily elevate pH up to 6), and a
      strong antacid model (a model of a case in which a strong antacid drug, such as
      magnesium hydroxide, was coadministered to temporarily elevate pH up to 8.0).
      These models were used to evaluate variation in pH-related absorption in humans.
      Dipyridamole preparation (Persantin tablets) and glibenclamide preparation
      (Euglucon tablets), both poorly water-soluble and pH-dependent soluble drugs,
      were chosen as model drugs to determine whether absorption is altered by changes
      in levels of gastric acid. The extent of absorption of dipyridamole was
      remarkably lower when gastric pH was continuously elevated to 6.0, whereas it was
      increased when gastric pH temporarily decreased to 1.8. The extent of absorption
      of glibenclamide increased dramatically when gastric pH temporarily increased to
      8.0, but did not change when gastric pH temporarily increased to 6.0. These
      results are consistent with reported results obtained in clinical studies. The
      results suggest that pH-related variations in absorption in humans can be
      accurately predicted using our new system.

PMID- 14648639
TI  - Investigation of molecular interactions between paclitaxel and DPPC by Langmuir
      film balance and differential scanning calorimetry.
AB  - Molecular interactions between paclitaxel and dipalmitoylphosphatidyl choline
      (DPPC) were investigated by Langmuir film balance and differential scanning
      calorimetry (DSC). Both the lipid monolayer at the air-water interface and that
      in the lipid bilayer vesicles (liposomes) were employed as model cell membranes.
      Thermodynamic and kinetic analyses of the DPPC/pacltaxel monolayer system and the
      paclitaxel penetration into the DPPC monolayer showed that DPPC and paclitaxel
      can form a nonideal miscible system in the lipid monolayer over a wide range of
      the DPPC/paclitaxel molar ratios. Paclitaxel exerts an area-condensing effect on
      the DPPC monolayer at small molecular areas and an area-expanding effect at large
      molecular areas on the pi-A behavior of the DPPC monolayer, which can be
      explained by the intermolecular forces and geometric accommodation between
      paclitaxel and DPPC. Based on a calculation of the excess free energy of the
      mixed monolayer system, the most stable state of the system occurs at the
      monolayer composition of 5% paclitaxel. Penetration kinetics showed that the
      paclitaxel penetration into the DPPC monolayer increases with increasing the drug
      concentration in the subphase, but there is a limit of approximately 500 ng/mL.
      Any further increase in paclitaxel concentration had no additional significant
      effects on the drug penetration. Differential scanning calorimetry showed that
      paclitaxel caused broadening of the main phase transition. There was no
      significant change in the peak melting temperature of the DPPC bilayers, which
      demonstrated that paclitaxel was localized in the outer hydrophobic cooperative
      zone of the bilayer.

PMID- 14648638
TI  - Transporter-mediated effects of diclofenamic acid and its ascorbyl pro-drug in
      the in vivo neurotropic activity of ascorbyl nipecotic acid conjugate.
AB  - Continuing our studies on SVCT2 ascorbic acid (AA) transporter-mediated drug
      delivery of neurotropic agents, we have now investigated the in vitro
      intracellular uptake of Diclofenac (Diclo) and its conjugate (AA-Diclo), both
      characterized by high affinity for the SVCT2 transporter. We have also
      investigated the in vivo uptake mechanism of AA-conjugate of Nipecotic acid (AA
      Nipec) and the implication of the transporter-mediated effects of Diclo and AA
      Diclo. Diclo resulted as a noncompetitive inhibitor of AA transport, but also
      showed a sodium-dependent and ascorbate-independent uptake, thus implying the
      possible involvement of specific transporters in the delivery to the brain of
      Diclo. This result opens a perspective in the discovery of new strategies in the
      targeting of this drug to the brain. Inhibitory effects of Diclo and AA-Diclo on
      the SVCT2 transporter were used to study anticonvulsant effects of AA-Nipec,
      confirming our hypothesis of an SVCT2-mediated transport in its neurotropic
      activity. AA-Diclo stability has been also investigated: it is hydrolyzed
      following a first-order kinetics in buffer, plasma (t(1/2) at about 10 h) and
      whole blood (t(1/2) at about 3 h), suggesting AA-Diclo as a potential candidate
      to enhance the short half-life of Diclo in vivo.

PMID- 14648640
TI  - Do multidrug resistance-associated protein-1 and -2 play any role in the
      elimination of estradiol-17 beta-glucuronide and 2,4-dinitrophenyl-S-glutathione
      across the blood-cerebrospinal fluid barrier?
AB  - The purpose of this study was to examine the role of multidrug resistance
      associated protein-1 and -2 (Mrp1 and Mrp2) in the efflux transport of organic
      anions across the blood-cerebrospinal fluid (CSF) barrier. The CSF concentration
      of estradiol-17beta-glucuronide (E(2)17betaG) and 2,4-dinitrophenyl-S-glutathione
      (DNP-SG) in the CSF after intracerebroventricular and intravenous injection were
      compared between wild-type and Mrp1 gene knockout mice. There was no significant
      difference in the apparent CSF elimination rate constants of E(2)17betaG (0.158
      and 0.145 min(-1)) and DNP-SG (0.116 and 0.0779 min(-1)) between wild-type and
      Mrp1 knockout mice, respectively. After intravenous administration of
      E(2)17betaG, its brain-to-serum and CSF-to-serum concentration ratios in Mrp1
      knockout mice were not significantly different from those in the wild-type.
      Results from in vivo and in vitro studies using Eisai hyperbilirubinemic rats, in
      which Mrp2 is hereditarily deficient, were similar to those using normal rats.
      Quantitative polymerase chain reaction (PCR) showed that the expression level of
      Mrp4 and Mrp5 was several times higher than that of Mrp1, whereas the expression
      levels of Mrp2, Mrp3, and Mrp6 were negligible or low. Therefore, Mrp4 and Mrp5
      may contribute to the efflux transport of E(2)17betaG and DNP-SG from the CSF.

PMID- 14648641
TI  - Compositional effects of cationic lipid/DNA delivery systems on transgene
      expression in cell culture.
AB  - Studies of the contribution of various physical properties of cationic lipid/DNA
      complexes (CLDCs) to their observed transgene expression in vitro were conducted
      using cationic liposomes composed of the cationic lipids 1,2-dioleoyl-3
      trimethylammonium propane (DOTAP) and dimethyldioctadecylammonium bromide (DDAB),
      with or without equimolar amounts of cholesterol (CHOL) or 1,2
      dioleoylphosphatidylethanolamine (DOPE). The relative degree of luciferase
      expression by CLDCs is dependent on a complex relationship between net charge of
      the CLDC as well as previously reported properties, such as membrane fluidity and
      curvature of the cationic bilayer. Assessments were made of the role of these
      physical properties on CLDC stability in the extracellular medium, the extent of
      DNA cellular association, and membrane disruption activity. The efficiency of
      luciferase expression from negatively charged CLDCs is greatly improved by
      incorporation of DOPE. This result correlates with enhanced resistance to
      inhibition of gene delivery by heparan sulfate, increased cellular association of
      DNA, and enhanced membrane disruption activity. Luciferase expression by
      positively charged CLDCs is greatly reduced by incorporating equimolar amounts of
      CHOL and DOPE. This result occurs is in spite of increased resistance to heparan
      sulfate-mediated inhibition of gene delivery, increased DNA cellular association,
      and enhanced membrane disruption activity. The observed CLDC compositional
      effects on luciferase expression along with observed effects on the delivery
      process suggest that a better understanding of the kinetics and specific routes
      of gene delivery is necessary.

PMID- 14648642
TI  - Increased physical stability and improved dissolution properties of itraconazole,
      a class II drug, by solid dispersions that combine fast- and slow-dissolving
      polymers.
AB  - Solid dispersions were prepared of itraconazole-Eudragit E100, itraconazole
      PVPVA64, and itraconazole-Eudragit E100/PVPVA64 using a corotating twin-screw hot
      stage extruder. Modulated temperature differential scanning calorimetry (MTDSC)
      was used to evaluate the miscibility of the extrudates, and dissolution
      experiments were performed in simulated gastric fluid without pepsin (SGF(sp)).
      Itraconazole and Eudragit E100 are miscible up to 13% w/w drug loading. From that
      concentration on, phase separation is observed. Pharmaceutical performance of
      this dispersion was satisfactory because 80% of the drug dissolved after 30 min.
      Extrudates of itraconazole and PVPVA64 were completely miscible but the
      pharmaceutical performance was low, with 45% of drug dissolved after 3 h.
      Combination of both polymers in different ratios, with a fixed drug loading of
      40% w/w, was evaluated. MTDSC results clearly indicated a two-phase system
      consisting of itraconazole-Eudragit E100 and itraconazole-PVPVA64 phases. In
      these extrudates, no free crystalline or glassy clusters of itraconazole were
      observed; all itraconazole was mixed with one of both polymers. The
      pharmaceutical performance was tested in SGF(sp) for different polymer ratios,
      and Eudragit E100/PVPVA64 ratios of 50/50 and 60/40 showed significant increases
      in dissolution rate and level. Polymer ratios of 70/30 and 80/20, on the other
      hand, had a release of 85% after 30 min. Precipitation of the drug was never
      observed. The combination of the two polymers provides a solid dispersion with
      good dissolution properties and improved physical stability compared with the
      binary solid dispersions of itraconazole.

PMID- 14648643
TI  - Polymer-drug compatibility: a guide to the development of delivery systems for
      the anticancer agent, ellipticine.
AB  - To establish a method for predicting polymer-drug compatibility as a means to
      guide formulation development, we carried out physicochemical analyses of polymer
      drug pairs and compared the difference in total and partial solubility parameters
      of polymer and drug. For these studies, we employed a range of biodegradable
      polymers and the anticancer agent Ellipticine as the model drug. The partial and
      total solubility parameters for the polymer and drug were calculated using the
      group contribution method. Drug-polymer pairs with different enthalpy of mixing
      values were analyzed by physicochemical techniques including X-ray diffraction
      and Fourier transform infrared. Polymers identified to be compatible [i.e.,
      polycaprolactone (PCL) and poly-beta-benzyl-L-aspartate (PBLA)] and incompatible
      [i.e., poly (d,l-lactide (PLA)], by the above mentioned methods, were used to
      formulate Ellipticine. Specifically, Ellipticine was loaded into PBLA, PCL, and
      PLA films using a solvent casting method to produce a local drug formulation;
      while, polyethylene oxide (PEO)-b-polycaprolactone (PCL) and PEO-b-poly (d,l
      lactide) (PLA) copolymer micelles were prepared by both dialysis and dry down
      methods resulting in a formulation for systemic administration. The drug release
      profiles for all formulations and the drug loading efficiency for the micelle
      formulations were also measured. In this way, we compared formulation
      characteristics with predictions from physicochemical analyses and comparison of
      total and partial solubility parameters. Overall, a good correlation was obtained
      between drug formulation characteristics and findings from our polymer-drug
      compatibility studies. Further optimization of the PEO-b-PCL micelle formulation
      for Ellipticine was also performed.

PMID- 14648644
TI  - Physicochemical and crystallographic characterization of mefenamic acid complexes
      with alkanolamines.
AB  - The preparation of mefenamic acid (MH)-alkanolamine (propanolamine,
      diethanolamine, triethanolamine) complexes was attempted to increase the
      transdermal flux of MH. Differential scanning calorimetry, Fourier transform
      infrared spectroscopy, and X-ray crystallographic studies demonstrated that MH
      and each alkanolamine formed an ion pair complex. The series of amine complexes
      had a lower melting point and higher solubility in water compared with pure MH.

PMID- 14648645
TI  - Visualization of the crystallization of lactose from the amorphous state.
AB  - The physical stability and solid-state recrystallization of spray-dried
      'amorphous' lactose particles were visualized using environmentally controlled
      atomic force microscopy (EC-AFM) and conventional optical microscopy. The
      morphology and crystalline state were investigated as a function of relative
      humidity (RH) and were correlated with bulk gravimetric vapor sorption
      measurements that were run in parallel. The metastable nature of amorphous spray
      dried lactose particles was apparent at low RHs (<30% RH). Visualization of the
      recrystallization transformation of amorphous lactose during moisture uptake at
      58 and 75% RH suggested only a proportion of the collapsed particles undergoes
      nucleation and crystal growth. The irregular surface morphology of the
      recrystallized particles suggested a secondary nucleation and growth process.
      Primary nucleation of alpha-lactose monohydrate within the non-recrystallized
      particles required exposure to elevated RH (94% RH). In relation to bulk
      measurements of moisture-induced amorphous recrystallization of spray-dried
      lactose, the results suggest that recrystallization of amorphous lactose, above a
      critical RH, may be induced by the presence of very low levels of a seed
      material, which may dramatically reduce the activation energy barrier for
      nucleation and crystal growth.

PMID- 14648646
TI  - New perspectives for visual characterization of pharmaceutical solids.
AB  - The utilization of descriptive image information in pharmaceutical powder
      technology is rather limited. Consequently, the development of this discipline is
      a challenge within physical characterization of pharmaceutical solids. The aim of
      this study was to develop and evaluate an inventive visual characterization
      approach for monitoring the granule growth in a fluidized-bed granulation process
      and to use the generated image information in the prediction of tabletting
      behavior of granules. Surface images of samples from 34 granulations were
      continuously captured during the spraying and drying phases of the process and
      particle size distributions were determined. The gray scale difference matrix
      (GSDM) was derived from two surface images taken in controlled illumination
      conditions. The particle size calculation from the surface images was based on a
      multivariate Partial Least Square (PLS) model between the GSDM and sieve analysis
      measurements. The image information of the end-point samples was also evaluated
      with respect to tabletting behavior of the granules produced. Principal component
      analysis (PCA) was used for data visualization. The introduced approach was
      suitable in particle size measurements of granules during all process phases and
      in the monitoring of different kinds of granule growth behavior. The visual
      inspection of the granule samples was powerful, enabling representational batch
      to-batch comparisons. The tabletting behavior of the granules could be predicted
      directly from particle size information generated from the surface images. PCA as
      a projection method was efficient in data visualization. Development of process
      analytical technologies (PAT) aims at improving the efficiency of processes. The
      presented visual characterization approach can be an effective process analytical
      tool in particle size analysis also enabling the evaluation of the further
      product quality in the end of the granulation process. The idea of
      characterization of bulk surface images opens new perspectives for
      characterization of pharmaceutical solids.

PMID- 14648647
TI  - Interspecies scaling of protein drugs: prediction of clearance from animals to
      humans.
AB  - The objective of this study was to evaluate the interspecies scaling for
      therapeutic protein drugs to predict the systemic clearance in humans from animal
      data. This study was undertaken to examine whether the rule of exponents of
      Mahmood and Balian for the prediction of clearance of nonprotein drugs can also
      be extended to macromolecules. Three different methods were used to predict
      clearance in humans: (1). clearance versus body weight (simple allometry), (2).
      the product of clearance and maximum life-span potential (MLP) versus body
      weight, and (3). the product of clearance and brain weight versus body weight.
      Data from 15 therapeutic proteins were analyzed, and the results indicated that
      the clearance of protein drugs can be predicted accurately using simple allometry
      or brain weight depending on the exponents of the simple allometry. Furthermore,
      these 15 drugs were scaled up using two species and the predicted clearance was
      compared with the predicted clearance obtained from more than two species. It was
      found that more than two species are needed for a reliable prediction of
      clearance.

PMID- 14648648
TI  - The effect of solvent on permeant diffusion through membranes studied using ATR
      FTIR and chemometric data analysis.
AB  - One method of improving the bioavailability of a topical formulation is to add an
      appropriate solvent that will act as a solubilizer for the permeant and, at the
      same time, modify the barrier properties of the stratum corneum. It has proved
      very difficult to determine the precise mechanisms of action involved; this is
      complicated by the concurrent diffusion of the solvent and the permeant into the
      skin. Under these circumstances the barrier function may well be changing as a
      function of time as the solvent disrupts it. We have observed this phenomenon in
      a model silicone membrane system that we have chosen to study initially to avoid
      the complexity of the heterogeneous nature of skin and its inherent biological
      variability. Diffusion experiments were conducted using an established ATR-FTIR
      approach but the data interpreted using sophisticated chemometric approaches that
      allowed us to deconvolve the IR signals from the permeant, the solvent, and the
      membrane. Data are presented that show the concurrent diffusion of benzoic acid
      (permeant), octanol (solvent), and how the octanol modifies the characteristics
      of the silicone membrane. Initial data are then presented using human skin to
      show the power of the diffusion approach coupled to the data deconvolution
      technique.

PMID- 14648649
TI  - Anticryptosporidial activity of furan derivative G1 and its inclusion complex
      with beta-cyclodextrin.
AB  - The capacity of beta-cyclodextrin (betaCD) to form a complex with a new furanic
      derivative, G1, was investigated. Interactions of the drug and betaCD in solution
      and in the solid state were studied using phase solubility techniques, thermal
      methods, X-ray, and IR spectroscopy. Preparation of a kneaded mix of G1/betaCD
      increased both the aqueous solubility and the dissolution rate of the furan
      derivative. The anticryptosporidial efficacies of the drug and of the inclusion
      complex were evaluated using a suckling murine model. Oral administration of G1
      considerably decreased the intensity of the infection, but betaCD showed similar
      anticryptosporidial activity to that of the betaCD-G1 complex and higher activity
      than G1 alone.

PMID- 14648650
TI  - Evaluation of in vivo bioequivalence methodology for topical clobetasol 17
      propionate based on pharmacodynamic modeling using Chinese skin.
AB  - The United States Food and Drug Administration recommends pilot dose duration
      response and pivotal bioequivalence studies to be conducted using reflectance
      colorimetry for assessment of the in vivo bioequivalence of topical dermatologic
      corticosteroids. The major objectives of the present studies were to examine the
      applicability of the standardized pharmacodynamic modeling-based methodology to
      super-potent clobetasol 17-propionate (CP) in the Chinese population and to
      evaluate the bioequivalence of two generic ointments and four generic creams
      containing 0.05% (w/w) CP with respect to Dermovate formulations using such
      methodology. In the pilot dose duration-response study, although the E(max) model
      (where E(max) is the maximum fitted value of AUEC, which is the area under the
      baseline-corrected, untreated control-site-corrected a* scale data from 0 to 24 h
      after drug removal) did not provide acceptable model fits, E(max) parameter
      estimates of -38.97 +/- 3.62 and -41.89 +/- 11.28 a*-scale. h, and ED(50) (dose
      duration required to achieve 50% of the fitted E(max) value) estimates of 0.40 +/
      0.37 and 0.42 +/- 0.16 h were obtained for Dermovate ointment and cream,
      respectively, by population analyses. The estimates for the two formulations were
      not statistically different, so in vivo bioequivalence studies were conducted at
      an ED(50)dose duration of approximately 0.5 h for both Dermovate formulations.
      The results demonstrated that one generic ointment was bioequivalent to
      Dermovate, whereas the other was not. None of the generic creams were shown to be
      bioequivalent to Dermovate cream. The in vivo bioequivalence data from the
      vasoconstriction assay were linearly correlated with stratum corneum uptake of
      the drug at the same dose duration until the maximal vasoconstriction response
      was achieved. The studies illustrated the applicability of the standardized
      pharmacodynamic modeling-based methodology in detecting the product differences
      between a variety of generic 0.05% CP formulations and reference Dermovate
      formulations in Chinese skin.

PMID- 14648651
TI  - Dielectric study of the molecular mobility and the isothermal crystallization
      kinetics of an amorphous pharmaceutical drug substance.
AB  - During the development of new pharmaceutical products based on drug substances in
      their amorphous form, the molecular mobility of an amorphous active ingredient
      was characterized in detail within a very broad time-temperature range. The
      relation between the isothermal crystallization kinetics and the dynamics of this
      amorphous substance was investigated. First, dynamic dielectric spectroscopy
      (DDS) and the thermostimulated current (TSC) techniques were used to analyze the
      molecular mobility of the amorphous drug substance over a wide frequency and
      temperature range (the drug substance is referred to as SSR in this text and was
      chosen as a model glass-forming system). Two relaxation processes, corresponding
      to different molecular motions, were identified. The beta(a)-relaxation process,
      associated with intramolecular oscillation of small dipolar groups, followed
      Arrhenius temperature behavior over the entire time-temperature domain that was
      studied. However, the main alpha(a)-relaxation process, assigned to the
      dielectric manifestation of the dynamic glass transition of the amorphous phase,
      was described by Vogel-Fulcher-Tammann (VFT) and Arrhenius behavior above and
      below the glass transition temperature (T(g)) respectively. The physical meaning
      of these complex dynamics is explained in the context of the Adam and Gibbs (AG)
      model, by the temperature dependence of the size of cooperatively rearranging
      regions (CRR) that govern the time scale of delocalized molecular motions. The
      distinction between the molecular mobility and the structural relaxation of
      amorphous systems below T(g) is discussed. This work shows that the complementary
      nature of both DDS and TSC techniques is essential to directly analyze the
      intramolecular and molecular motions of disordered phases over a wide time
      temperature range above and below the T(g). Second, real-time dielectric
      measurements were carried out to determine the isothermal crystallization
      kinetics of the SSR amorphous drug. Whatever the crystalline form obtained over
      time in the crystallization process, the decrease of the dielectric response of
      amorphous phase, which is characteristic of the isothermal crystallization, was
      studied to monitor the time dependence of the degree of crystallinity. The
      characteristic crystallization time, derived from Kohlrausch-Williams-Watt (KWW)
      Avrami analyses performed at different temperatures, followed an Arrhenius
      temperature dependence. Behaviors specific to the molecular mobility of the
      amorphous drug substance were compared with the characteristic crystallization
      time. It was concluded that the crystal growth process of the SSR drug seems to
      be controlled by the intramolecular motions involving the beta(a)-relaxation mode
      and not by the molecular motions responsible for the alpha(a)-relaxation mode in
      the range of temperatures >T(g). Subsequent studies will focus on the
      crystallization process of the SSR drug in the glassy state (T < T(g)).

PMID- 14648654
TI  - Not just angiogenesis--wider roles for the angiopoietins.
AB  - Since the discovery of the angiopoietins, much interest has been focused on their
      biological actions and their potential use as therapeutic targets. It is
      generally accepted that the angiopoietins play an important role in angiogenesis
      and hence are described as angiogenic factors. However, it is becoming
      increasingly clear that this is not their only role and it is likely that the
      angiopoietins have important roles in a wider range of biological and
      pathological functions.

PMID- 14648655
TI  - New insights into the roles of matrix metalloproteinases in colorectal cancer
      development and progression.
AB  - This review outlines new concepts that are emerging for the functions of matrix
      metalloproteinases in colorectal cancer development and progression. The two main
      concepts that will be discussed are the role of matrix metalloproteinases in the
      early stages of colorectal tumour development and the functional mechanisms by
      which matrix metalloproteinases contribute to colorectal tumour invasion and
      metastasis. The matrix metalloproteinases are a group of enzymes, which have been
      best characterized for their ability to degrade extracellular matrix proteins and
      thus they have been extensively studied in tumour invasion. It is now becoming
      recognized that the matrix metalloproteinases have key roles in a variety of
      biological processes that are distinct from their well-defined role in matrix
      degradation. This group of enzymes has been shown to interact with a broad range
      of non-matrix proteins including growth factors and their receptors, mediators of
      apoptosis, and cell adhesion molecules. The elucidation of novel biological roles
      for the matrix metalloproteinases also challenges the current predominant concept
      of matrix metalloproteinases as enzymes only involved in matrix degradation.
      Recent studies have shown that several matrix metalloproteinases, especially
      matrilysin (MMP-7), interact with the specific molecular genetic and signalling
      pathways involved in colorectal cancer development. In particular, matrilysin is
      activated at an early stage of colorectal tumourigenesis by the beta-catenin
      signalling pathway. Furthermore, studies are now elucidating specific mechanisms
      by which individual matrix metalloproteinases, especially membrane-type matrix
      metalloproteinases, interact with specific cell adhesion molecules and
      cytoskeletal proteins and thus contribute dynamically to colorectal tumour
      invasion.

PMID- 14648656
TI  - The presence of high-risk HPV combined with specific p53 and p16INK4a expression
      patterns points to high-risk HPV as the main causative agent for adenocarcinoma
      in situ and adenocarcinoma of the cervix.
AB  - Adenocarcinoma in situ (ACIS) and adenocarcinoma (AdCA) of the cervix are
      frequently missed in population-based screening programmes. Adding high-risk HPV
      (hrHPV) testing to cervical cancer screening might improve the detection rate of
      ACIS and AdCA. Since the exact proportion of AdCAs of the cervix that can be
      attributed to hrHPV infection is still a matter of debate, a comprehensive study
      was performed of hrHPV presence in ACIS and AdCA of the cervix. Archival formalin
      fixed specimens of indisputable ACIS (n=65) and AdCA (n=77) of the cervix were
      tested for hrHPV DNA by GP5+/6+ PCR-enzyme immunoassay (EIA) and type-specific E7
      PCR for 14 hrHPV types. Further immunostaining for p16INK4A and p53 was performed
      to assess alternative pathways of carcinogenesis potentially unrelated to HPV.
      hrHPV DNA was found in all (100%) ACISs and 72 (94%) cervical AdCAs, whereas none
      of 20 endometrial AdCAs scored hrHPV-positive. HPV 18 was most prevalent and
      found as single or multiple infection in 68% of ACISs and 55% of cervical AdCAs.
      Diffuse immunostaining for p16INK4a, a potential marker of hrHPV E7 function, was
      significantly more frequent in hrHPV-positive cervical AdCAs (19/20; 95%) than in
      those without hrHPV (1/5; 20%; p<0.001). Immunostaining for p53, pointing to
      stabilized wild-type or mutant p53 protein, was significantly more frequent in
      hrHPV cervical AdCAs negative for hrHPV (p=0.01). No difference in p16INK4a and
      p53 immunostaining was found between hrHPV-negative cervical AdCAs and
      endometrial AdCAs. Hence, only a minority of cervical AdCAs displayed absence of
      HPV DNA and immunostaining profiles suggestive of an aetiology independent of
      HPV. Since all ACISs and nearly all cervical AdCAs were hrHPV-positive, the
      incorporation of hrHPV testing in cervical cancer screening programmes is likely
      to decrease markedly the incidence of cervical AdCA.

PMID- 14648657
TI  - Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their
      receptor VEGFR-3, during different stages of cervical carcinogenesis.
AB  - Cervical carcinogenesis has well-defined stages of disease progression including
      three grades of pre-invasive lesions--cervical intraepithelial neoplasia grades 1
      3 (CIN 1-3)--and invasive cervical cancer. However, the biological properties of
      CIN lesions prone to develop invasive disease are not well defined. Recent
      observations suggest that early invasive disease spreads to regional lymph nodes
      in several tumour types and that growth factors (VEGF-C and VEGF-D) involved in
      new lymphatic vessel formation may play a crucial role in this process. The
      present study has assessed the expression of VEGF-C and VEGF-D, and their
      receptor VEGFR-3, in 152 cervical lesions (33 CIN 1, 33 CIN 2, 37 CIN 3, and 49
      squamous cell carcinomas) to determine whether expression of lymphangiogenic
      factors occurs prior to invasion. The presence of lymphatic vessels was
      determined using LYVE-1 and podoplanin staining, as well as double immunostaining
      for LYVE-1/CD34 and podoplanin/CD34. In situ hybridization was performed to
      determine VEGFR-3 mRNA expression. A significant positive correlation was found
      between VEGF-C, VEGF-D, and VEGFR-3 expression through the different stages of
      cervical carcinogenesis. Significant differences in protein expression for VEGF
      C, VEGF-D, and VEGFR-3 were found between CIN 1-2 and CIN 3 (p<0.001 for all),
      but not between CIN 3 and cervical cancer. More than 50% of the CIN 3 lesions
      showed moderate to strong staining for VEGF-C and VEGF-D, whereas most of the
      early pre-cancerous lesions (CIN 1 and 2) were negative. In cervical cancer,
      similar observations to those in CIN 3 were found. VEGFR-3 mRNA expression was
      found in the cytoplasm of epithelial neoplastic cells and VEGFR3 protein
      expression was found in more than 50% of CIN 3 lesions and cervical cancers,
      compared with 15% in CIN 1 and 2. These findings suggest an autocrine growth
      stimulation pattern via VEGFR-3. Adjacent CIN 3 was present in nine cervical
      cancers and displayed strong expression for VEGF-C, VEGF-D, and VEGFR-3. These
      results suggest that in cervical carcinogenesis a switch to the lymphangiogenic
      phenotype may occur at the stage of CIN 3.

PMID- 14648658
TI  - In lymph node-negative invasive breast carcinomas, specific chromosomal
      aberrations are strongly associated with high mitotic activity and predict
      outcome more accurately than grade, tumour diameter, and oestrogen receptor.
AB  - The objectives of this study were to analyse whether specific chromosomal gains
      and losses in lymph node-negative breast cancer correlate with other features and
      to evaluate their prognostic value. Seventy-six lymph node-negative breast
      carcinomas (median follow-up 46 months; range 9-105 months) were used.
      Histological grade, tumour type, maximal tumour diameter, oestrogen/progesterone
      receptor (ER/PR), mitotic activity index (MAI), and mean nuclear area (MNA) were
      assessed. Whole genome DNA analysis was performed by comparative genomic
      hybridization (CGH). Chromosomal aberrations were compared with classical and
      other prognostic features. Kaplan-Meier curves and multivariate survival analysis
      (Cox model) were used to assess the prognostic value of the CGH and other data.
      Fifteen (21.4%) out of 70 patients (six cases were lost to follow-up) developed
      locoregional (n=3) or distant metastases (n=12). The following criteria were
      prognostic for (any) recurrence (in decreasing significance): 3q gain,
      simultaneous gain at 1q and 8q, MAI < versus > or =10, MNA < versus > or =63
      microm. Loss of 1p occurred significantly more often in the large group of ductal
      breast carcinomas with a MAI > or =10 (n=38) than in cancers with a MAI<10.
      Moreover, 8/15 (53%) patients with recurrences had a gain at 3q, as opposed to
      three (5.5%) of the 55 recurrence-free patients. This association was even
      stronger in ductal carcinomas (hazard ratio=10.9, p<0.0001). Cox regression
      revealed that the 3q gain was the strongest prognostic factor; other features did
      not have additional prognostic value. In conclusion, loss of 1p is associated
      with a high MAI. A gain of 3q is a stronger predictor of recurrence than grade,
      MAI, and other features in invasive breast cancers.

PMID- 14648659
TI  - Primary breast myoepithelial cells exert an invasion-suppressor effect on breast
      cancer cells via paracrine down-regulation of MMP expression in fibroblasts and
      tumour cells.
AB  - In normal breast and ductal carcinoma in situ, myoepithelial cells form an
      incomplete layer separating the epithelial compartment from the stromal
      environment. Transition to invasive disease is marked by penetration of the
      myoepithelial-basement membrane (BM) interface. One mechanism involved in tumour
      invasion is breakdown of extracellular matrices by matrix metalloproteinases
      (MMPs). It was hypothesized that myoepithelial cells may modulate tumour invasion
      by controlling MMP gene expression, both in tumour cells and in peri-ductal
      fibroblasts. To investigate this, myoepithelial cells from normal breast were
      purified and characterized and their effect on tumour cell invasive potential was
      assessed. The effect on MMP gene expression of breast cancer cells cultured alone
      or in combination with primary normal breast fibroblasts was also analysed using
      RT-PCR with ELISA quantitation, with zymographic analysis to measure enzyme
      activity. Normal breast myoepithelial cells significantly reduced invasion by the
      breast cancer cell lines MCF-7, T47D, MDA-MB 231, and MDA-MB 468 when they were
      cultured alone or in the presence of a fibroblast population. Reduced invasion
      was associated with changes in MMP gene expression. In those tumour cells
      expressing MMP, there was a significant down-regulation of MMP-2 (MDA-MB 468,
      p<0.001), MMP-9 (MDA-MB 231, p=0.05; MDA-MB 468, p<0.001), and MT1-MMP (p<0.001
      for both MDA-MB 231 and MDA-MB 468). Myoepithelial cells also caused a
      significant decrease in MMP gene expression in co-cultured fibroblasts.
      Furthermore, this was associated with reduced gelatinolytic activity as
      identified by zymography. This study demonstrates for the first time that primary
      myoepithelial cells from normal breast reduce breast cancer cell invasion and
      that this is mediated via modulation of both tumour cell and fibroblast function.
      This emphasizes the importance of the myoepithelial cell in controlling the
      breast microenvironment and focuses on the potential significance of the loss of
      this population with disease progression.

PMID- 14648660
TI  - Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of
      the breast; correlation of BNip3 levels with necrosis and grade.
AB  - Ductal carcinoma in situ (DCIS) of the breast is an early, non-invasive lesion
      and the prognosis is associated with the extent of necrosis and cell death within
      the tumour. Two cell death genes, BNip3 and NIX, are up-regulated in response to
      hypoxia in breast carcinoma cells, although any involvement of either gene in
      disease progression is currently unknown. This study has analysed the expression
      of BNip3 and NIX in 56 samples of breast DCIS, as well as in adjacent benign and
      invasive breast tissue. Both genes are strongly expressed in the epithelial
      component of a subset of DCIS and invasive disease. The data show a correlation
      between high expression of BNip3 in the DCIS cells and a high-grade, necrotic
      lesion that is likely to be associated with invasive tumour. BNip3 was present in
      tumour-associated macrophages and in apocrine metaplastic lesions. Expression of
      NIX did not correlate with any of the parameters investigated.

PMID- 14648661
TI  - Altered expression of the septin gene, SEPT9, in ovarian neoplasia.
AB  - The septin family of genes has been implicated in a variety of cellular processes
      including cytokinesis, membrane transport and fusion, exocytosis, and apoptosis.
      One member of the septin family maps to chromosome 17q25.3, a region commonly
      deleted in sporadic ovarian and breast tumours, and has also been identified as a
      fusion partner of MLL in acute myeloid leukaemias. The present study demonstrates
      that the pattern of expression of multiple splice variants of this septin gene is
      altered in ovarian tumours and cell lines. In particular, expression of the zeta
      transcript is detectable in the majority of tumours and cell lines, but not in a
      range of non-malignant adult and fetal tissues. Zeta expression is accompanied by
      loss of the ubiquitous beta transcript. Somatic mutations of the gene were not
      detected in ovarian tumours, but it was demonstrated that beta expression in
      tumour cell lines can be reactivated by 5-azacytidine treatment, suggesting a
      role for methylation in the control of expression of this gene.

PMID- 14648662
TI  - Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma.
AB  - Cyclin E overexpression occurs in a subset of endometrial carcinomas (ECs), but
      the molecular mechanisms underlying this alteration remain to be established. The
      present study has analysed amplification of the cyclin E gene (CCNE) and mutation
      in hCDC4, the gene coding for the F-box protein, which tags phosphorylated cyclin
      E for proteosomal degradation, to ascertain whether these alterations might be
      responsible for cyclin E overexpression in ECs. Cyclin E and p53 expression was
      studied by immunohistochemistry in eight atypical endometrial hyperplasias
      (AEHs), 51 endometrioid endometrial carcinomas (EECs), and 22 non-endometrioid
      endometrial carcinomas (NEECs). CCNE amplification was analysed by fluorescence
      in situ hybridization (FISH). Mutations in exons 2-11 of the hCDC4 gene were
      screened by PCR-SSCP-sequencing. Finally, the polymorphic marker D4S1610 was used
      to assess loss of heterozygosity (LOH) in the hCDC4 gene. Cyclin E overexpression
      was found in 26/81 (32%) cases and was associated with the histological type of
      the lesion, since it was not found in any AEHs but was present in 27% of EECs and
      54.5% of NEECs (p=0.035). Cyclin E overexpression was associated with
      histological grade (p=0.011) and p53 immunostaining in EECs (p=0.033). CCNE
      amplification was found in 6 of 37 (16%) ECs examined. There was a significant
      association between CCNE amplification and the histological type of the lesion,
      since five (83%) of the six cases with amplification were NEECs (p=0.008). One
      EEC harboured an hCDC4 mutation: a CGA to CAA (Arg/Gln) change at codon 479. In
      addition, D4S1610 LOH was found in 7 of 23 (30%) informative cases analysed, but
      no correlation with cyclin E overexpression was found. However, the tumour with
      hCDC4 mutation also showed LOH. This is the first study demonstrating that cyclin
      E overexpression is associated with gene amplification in ECs, these alterations
      being more frequent in NEECs. Although hCDC4 exhibits a low mutation frequency in
      ECs overexpressing cyclin E, it seems to function as a tumour suppressor gene
      that is involved in endometrial carcinogenesis.

PMID- 14648663
TI  - Long-term infection with Helicobacter felis and inactivation of the tumour
      suppressor gene p53 cumulatively enhance the gastric mutation frequency in Big
      Blue transgenic mice.
AB  - The aims of this study were to determine whether colonization with Helicobacter
      felis resulted in the accumulation of mutations within murine gastric tissue and
      whether the degree of genetic damage was increased by p53 deficiency. Female
      C57BL/6 mice carrying either the lambda/lacI transgene (Big Blue transgenic mice)
      or the lambda/lacI transgene and deficient in one allele of the p53 tumour
      suppressor gene (TSG-p53/Big Blue) were inoculated with H felis. Seven months
      after inoculation, mutations in the target lacI gene were assessed using the Big
      Blue transgenic mutagenesis assay system in these animals and in controls. There
      was an approximately two-fold increase in lacI mutations in gastric mucosa
      harvested from mice infected with H felis and also from non-infected mice
      heterozygous for the p53 allele relative to wild-type mice. The mutation
      frequency in mice infected with H felis and deficient in one allele of p53 was
      increased approximately three-fold. Active gastric inflammation was significantly
      greater in H felis-infected p53 hemizygous mice compared with H felis p53 wild
      type mice. Gastric epithelial proliferation was similarly increased with
      infection in both of these latter groups of mice. In infected mice, there was a
      significant correlation between the mutation frequency and the degree of active
      gastric inflammation. These data suggest a synergistic action between infection
      with H felis and p53 deficiency in the accumulation of mutations within gastric
      tissue. Active neutrophil infiltration in gastric Helicobacter infection may
      contribute to the increased levels of mutation observed.

PMID- 14648664
TI  - High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1,
      FGF3, FGF4, EMS1) in urinary bladder cancer.
AB  - Gene amplification is a common mechanism for oncogene overexpression. High-level
      amplifications at 11q13 have been repeatedly found in bladder cancer by
      comparative genomic hybridization (CGH) and other techniques. Putative candidate
      oncogenes located in this region are CCND1 (PRAD1, bcl-1), EMS1, FGF3 (Int-2),
      and FGF4 (hst1, hstf1). To evaluate the involvement of these genes in bladder
      cancer, a tissue microarray (TMA) containing 2317 samples was screened by
      fluorescence in situ hybridization (FISH). The frequency of gains and
      amplifications of all genes increased significantly from stage pTa to pT1-4 and
      from low to high grade. In addition, amplification was associated with patient
      survival and progression of pT1 tumours. Among 123 tumours with amplifications,
      68.3% showed amplification of all four genes; 19.5% amplification of CCND1, FGF4,
      and FGF3; and 0.8% co-amplification of FGF4, FGF3, and EMS1. Amplification of
      CCND1 alone was found in 9% of the tumours, while EMS1 alone was amplified in
      1.6% and FGF4 in 0.8%. Overall, the amplification frequency decreased with
      increasing genomic distance from CCND1, suggesting that, among the genes
      examined, CCND1 is the major target gene in the 11q13 amplicon in bladder cancer.

PMID- 14648665
TI  - NOV (CCN3) regulation in the growth plate and CCN family member expression in
      cartilage neoplasia.
AB  - Growth plate chondrocytes undergo a coordinated differentiation process resulting
      in terminal differentiation and new bone formation. Enchondromas are pre
      malignant, benign cartilaginous lesions that arise from growth plate chondrocytes
      that fail to undergo terminal differentiation. NOV (nephroblastoma overexpressed)
      is a member of the CCN family of proteins, which share a common multi-modular
      organization. While the role of NOV in chondrocyte development and cartilage
      neoplasia is not known, other CCN family members play a role in chondrocyte
      differentiation, or are differentially regulated in cartilage neoplasia. In
      embryonic murine growth plates, NOV was expressed in pre-hypertrophic and early
      hypertrophic chondrocytes. PTHrP treatment (which inhibits terminal
      differentiation) decreased NOV expression in murine femurs maintained in organ
      culture, and decreased the activity of a NOV reporter construct in vitro.
      Expression of the CCN family members NOV, CTGF, CYR61, and WISP-1 was examined in
      15 chondrosarcomas of various grades and in three enchondromas. Expression of all
      of the family members was lower in the higher-grade tumours. As identification of
      the grade of cartilage neoplasia can sometimes be difficult using histology
      alone, the level of expression of CCN family members could be a useful adjunct in
      the determination of tumour grade.

PMID- 14648666
TI  - Productive infection of dendritic cells by simian immunodeficiency virus in
      macaque intestinal tissues.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that likely play
      multiple roles in human immunodeficiency virus-1 (HIV-1) and simian
      immunodeficiency virus (SIV) pathogenesis. This paper describes the effects of
      pathogenic SIV infection on the networks of DCs in rhesus macaque (Macaca
      mulatta) intestinal tissues. Intestinal tissues were obtained from macaques at
      different stages of disease following infection with the pathogenic SIV/DeltaB670
      isolate. The patterns and levels of expression of SIV and DC-associated mRNAs
      were examined and quantitated directly in intestinal tissue sections. In situ
      hybridization was performed for SIV, DC-specific ICAM3-grabbing non-integrin (DC
      SIGN), DC-specific lysosome-associated membrane glycoprotein (DC-LAMP), DC
      specific C-type lectin 1 (DECTIN-1), CC chemokine receptor 6 (CCR6), CCR7, and
      macrophage inflammatory protein 3alpha (MIP-3alpha/CCL20) mRNAs and quantitative
      image analysis was performed to measure mRNA expression levels. To identify the
      cell types productively infected by SIV, simultaneous in situ hybridization and
      immunohistochemical staining were performed. The DC networks in macaque
      intestinal tissues were found to be extensive and although they generally
      remained intact during the course of SIV infection, there were alterations in the
      expression of markers for immature DCs. One alteration was an increase in the
      expression in intestinal submucosa of DC-SIGN, a molecule that binds to HIV-1/SIV
      and increases its infectivity. Concomitant with this increase, it was found that
      during AIDS, the population of productively infected cells included DCs, based on
      co-expression of DC-SIGN and DECTIN-1 mRNAs. These data indicate that SIV
      infection affects subpopulations of macaque intestinal DCs, including productive
      infection of DC-SIGN+ DCs, the consequences of which are likely to be ongoing
      viral propagation and decreased immunostimulatory function.

PMID- 14648667
TI  - Re: Sedivy et al. Short-term rhythmic proliferation of human breast cancer cell
      lines: surface effects and fractal growth patterns. J Pathol 2002; 197: 163-169.

PMID- 14648669
TI  - Integrins in regulation of tissue development and function.
AB  - Cell adhesion is indispensable for embryonic development and for proper tissue
      function. In metazoans, integrins are the major adhesion receptors that connect
      cells to components of the extracellular matrix. Integrins are implicated in
      assembly of extracellular matrices, cell adhesion and migration on extracellular
      matrices, and in vertebrates (in which the integrin family has expanded) they can
      also mediate cell-cell adhesion. Furthermore, integrin-mediated adhesion can
      modulate many different signal transduction cascades and support cell survival,
      proliferation, and influence the expression of differentiation-related genes. In
      this review we briefly explain how integrins can affect so many different aspects
      of cell behavior and discuss evidence for roles of integrins in tissue
      development, function, and disease.

PMID- 14648670
TI  - Ultrastructural localization of spicule matrix proteins in normal and
      metalloproteinase inhibitor-treated sea urchin primary mesenchyme cells.
AB  - Studies of the sea urchin larval skeleton have contributed greatly to our
      understanding of the process of biomineralization. In this study we have
      undertaken an investigation of the morphology of skeleton formation and the
      localization of proteins involved in the process of spicule formation at the
      electron microscope level. Sea urchin primary mesenchyme cells undergo a number
      of morphological changes as they synthesize the larval skeleton. They form a
      large spicule compartment that surrounds the growing spicule and, as spicule
      formation comes to an end, the density of the cytoplasm decreases. Inhibition of
      spicule formation by specific matrix metalloproteinase inhibitors or serum
      deprivation has some subtle effects on the morphology of cells and causes the
      accumulation of specific classes of vesicles. We have localized proteins of the
      organic matrix of the spicule and found that one protein, SM30, is localized to
      the Golgi apparatus and transport vesicles in the cytoplasm as well as throughout
      the occluded protein matrix of the spicule itself. This localization suggests
      that SM30 is an important structural protein in the spicule. Another spicule
      matrix protein, SM50, has a similar cytoplasmic localization, but in the spicule
      much of it is localized at the periphery of the spicule compartment, and
      consequently it may play a role in the assembly of new material onto the growing
      spicule or in the maintenance of the integrity of the matrix surrounding the
      spicule.

PMID- 14648671
TI  - Protein synthesis is required for the transition to Ca(2+)-dependent regulated
      secretion in progesterone-matured Xenopus oocytes.
AB  - Calcium (Ca) ionophores trigger cortical granule exocytosis in progesterone
      matured Xenopus oocytes (eggs), but not in immature oocytes. Prior work suggested
      that this secretory transition involved a Ca-dependent isoform of protein kinase
      C (PKC). To address this possibility, we treated eggs with several different
      inhibitors of Ca-dependent PKCs. Although these agents (eg., staurosporine, Ro31
      8220) completely blocked cortical granule exocytosis that is triggered in eggs by
      phorbol esters, they had no impact on ionomycin-evoked secretion of cortical
      granule lectin. These data suggest that Ca-dependent PKCs do not mediate
      secretory triggering in eggs. Instead, further investigation revealed that
      protein synthesis (but not RNA synthesis) was required for eggs to secrete in
      response to ionomycin. Moreover, we observed that when oocytes were matured by
      injection of maturation promoting factor (MPF), they failed to secrete in
      response to ionomycin. Collectively, these results suggest that the progesterone
      dependent maturation pathway induces these cells either to synthesize de novo, a
      protein that mediates Ca-dependent secretory triggering, or that intrinsic Ca
      sensing machinery is modified in a protein-synthesis-dependent fashion. Initial
      efforts to distinguish between these possibilities (using Ca overlay,
      pharmacological and immunoblot strategies) revealed that such Ca-binding proteins
      as calmodulin, synaptotagmin1, CAPS, rabphilin-3A and calcineurin were unlikely
      to transduce the secretory effects of ionomycin in eggs. Thus, the cortical
      reaction in these cells may rely on a novel mechanism for initiating Ca-dependent
      exocytosis.

PMID- 14648672
TI  - Is re-feeding efficiency compromised by prolonged starvation during aestivation
      in the green striped burrowing frog, Cyclorana alboguttata?
AB  - We examined several morphological parameters of the gastrointestinal tract,
      digesta passage rates, and nutrient assimilation efficiencies of Green-striped
      Burrowing frogs (Cyclorana alboguttata) following prolonged fasting during three
      months of aestivation and compared these with frogs that had been continuously
      fed. Whole animal digesta passage rates were significantly reduced following
      three months aestivation as a result of a decreased digesta evacuation rate from
      the stomach. Furthermore, food was selectively retained in the small intestine
      for an increased time following three months of aestivation. Overall
      digestibility of food and nitrogen, carbon, and energy extraction efficiencies
      were not significantly different from control values following three months of
      aestivation. These findings suggest that C. alboguttata employs reduced digesta
      passage rates so as to maximize nutrient assimilation efficiency following
      prolonged food deprivation during aestivation.

PMID- 14648673
TI  - Muscle enzyme activities in a deep-sea squaloid shark, Centroscyllium fabricii,
      compared with its shallow-living relative, Squalus acanthias.
AB  - The activities of several enzymes of energy metabolism were measured in the
      heart, red muscle, and white muscle of a deep and a shallow living squaloid
      shark, Centroscyllium fabricii and Squalus acanthias, respectively. The
      phylogenetic closeness of these species, combined with their active predatory
      nature, similar body form, and size makes them well matched for comparison. This
      is the first time such a comparison has been made involving a deep-sea
      elasmobranch. Enzyme activities were similar in the heart, but generally lower in
      the red muscle of C. fabricii. Paralleling the trend seen in deep-sea teleosts,
      the white muscle of C. fabricii had substantially lower activities of key
      glycolytic enzymes, pyruvate kinase and lactate dehydrogenase, relative to S.
      acanthias or other shallow living elasmobranchs. Unexpectedly, between the
      squaloid sharks examined, creatine phosphokinase activity was higher in all
      tissues of the deep living C. fabricii. Low white muscle glycolytic enzyme
      activities in the deep-sea species coupled with high creatine phosphokinase
      activity suggests that the capacity for short burst swimming is likely limited
      once creatine phosphate supplies have been exhausted.

PMID- 14648674
TI  - Refrigeration of rainbow trout gametes and embryos.
AB  - Prolonged access to early embryos composed of undifferentiated, totipotent
      blastomeres is desirable in situations when multiple collections of gametes are
      not possible. The objective of the present study is to examine whether the
      refrigeration of rainbow trout Oncorhynchus mykiss gametes and early embryos
      would be a suitable, reliable, and efficient tool for prolonging the availability
      of early developmental stages up to the advanced blastula stage. The study was
      conducted continuously during fall, winter, and spring spawning seasons. In all,
      more than 500 experimental variants were performed involving individual samples
      from 26 females and 33 males derived from three strains. These strains
      represented three possible circumstances. In optimal one, gametes from good
      quality donors were obtained soon after ovulation. In the two non-optimal
      sources, either donors were of poor genetic quality or gametes were collected
      from a distant location and transported as unfertilized gametes. A highly
      significant effect of variability of individual sample quality on efficiency of
      gamete and embryo refrigeration was revealed. The source of gametes significantly
      affected viability of refrigerated oocytes and embryos, but not spermatozoa. On
      average, oocytes from optimal source retained full fertilization viability for
      seven days of chilled storage, significantly longer than from non-optimal
      sources. Spermatozoa, regardless of storage method, retained full fertilization
      ability for the first week of storage. Refrigeration of embryos at 1.4+/-0.4
      degrees C significantly slowed the development. Two- week-old embryos were still
      in blastula stage. Average survival rate of embryos refrigerated for 10 days and
      then transferred to regular incubation temperatures of 9-14 degrees C was 92% in
      optimal and 51 and 71% in non-optimal source variants. No effect of gamete and
      embryo refrigeration on the occurrence of developmental abnormalities was
      observed. Cumulative refrigeration of oocytes and embryos resulted in an average
      embryo survival rate of 71% in optimal source variants after 17 days of
      refrigeration (7 days oocytes+10 days embryos). The study shows that both gamete
      and embryo refrigeration can be successfully used as an efficient tool for
      prolonging availability of rainbow trout embryos in early developmental stages.

PMID- 14648675
TI  - Estimate and production of milk energy in two subspecies of red deer: Cervus
      elaphus hispanicus and C. e. scoticus.
AB  - This study estimates the caloric value of red deer milk as assessed relating bomb
      calorimetry data with the main milk nutrients. The study also examines milk
      energy estimates and lactation variables to compare Iberian red deer hinds
      (Cervus elaphus hispanicus) and the most studied Scottish red deer (C. e.
      scoticus). The final model predicted energy value (Ecal) in kcal/g of fresh milk
      from fat (F) and protein (P) content of milk, but not lactose: Ecal = 0.345 +
      8.332 F + 5.403 P. Energy content per gram of milk increased with lactation stage
      but there was no difference between subspecies. However, subspecies differed in
      the daily and total energy production. Although milk energy values appeared to
      differ with estimates following the most used model developed from livestock,
      milk energy of deer estimated by both methods showed a very high correlation with
      each other, and both yielded also similar correlation coefficients with the
      remaining lactation variables. Calf gains showed a greater correlation with mean
      protein content and total protein yield, than with total energy yield or other
      milk nutrients. Milk protein appears to be more relevant to calf growth than
      gross energy yield.

PMID- 14648676
TI  - Dye coupling without gap junctions suggests excitatory connections of gamma
      aminobutyric acidergic neurons.
AB  - After injections of the low-molecular-weight tracer neurobiotin into the
      preeminential nucleus of the brain of the mormyrid fish Gnathonemus petersii, we
      observed that retrogradely labeled, large fusiform projection neurons (LFd cells)
      of the deep granular layer of the electrosensory lobe (ELL) were surrounded by 30
      50 labeled satellite granular cells. More superficially located projection cells,
      including large fusiform cells in the superficial granular layer (LFs) and large
      ganglionic (LG) cells in the ganglionic layer, were never surrounded by labeled
      satellites. LFd-satellite cells have a small soma (diameter 5-8 microm), a few
      small dendrites, and an apical axon that terminates in the plexiform and
      ganglionic layers of the ELL. They contact LFd projection neurons with
      dendrodendritic, dendrosomatic, and somatodendritic puncta adhaerentia-like
      appositions, designated here as "neurapses." In the electron microscope, these
      contacts resemble synapses without presynaptic vesicles. Because no gap junctions
      were found between LFd and satellite granule cells, we suggest that the neurapses
      allow the passage of neurobiotin, though not biocytin or biotinylated dextran
      amine. These contacts may provide the intermediate substrate for the postulated,
      but so far unknown, excitatory connection between primary afferent input and LFd
      projection neurons, via gamma-aminobutyric acid (GABA)-ergic granular cells. We
      suggest that certain puncta adhaerentia-like contacts might not be only adhesive
      structures and that LFd-satellite granular cells might both excite LFd projection
      cells via neuraptic contacts of their dendrites and cell bodies and inhibit more
      superficial LF and LG cells via their GABAergic axonal synapses. Our results
      suggest that puncta adhaerentia-like contacts could be responsible in some cases
      for the electrical coupling found electrophysiologically in local inhibitory
      circuits.

PMID- 14648677
TI  - Developmental distribution of reelin-positive cells and their secreted product in
      the rodent spinal cord.
AB  - To date, only sympathetic and parasympathetic preganglionic neurons are known to
      migrate abnormally in reeler mutant spinal cord. Reelin, the large extracellular
      matrix protein absent in reeler, is found in wild-type neurons bordering both
      groups of preganglionic neurons. To understand better Reelin's function in the
      spinal cord, we studied its developmental expression in both mice and rats. A
      remarkable conservation was found in the spatiotemporal pattern of Reelin in both
      species. Numerous Reelin-expressing cells were found in the intermediate zone,
      except for regions containing somatic and autonomic motor neurons. A band of
      Reelin-positive cells filled the superficial dorsal horn, whereas only a few
      immunoreactive cells populated the deep dorsal horn and dorsal commissure. High
      levels of diffuse Reelin product were detected in the lateral marginal and
      ventral ventricular zones in both rodent species. This expression pattern was
      detected at all segmental spinal cord levels during embryonic development and
      remained detectable at lower levels throughout the first postnatal month. To
      discriminate between the cellular and secreted forms of Reelin, brefeldin A was
      used to block secretion in organotypic cultures. Such perturbations revealed that
      the high levels of secreted Reelin in the lateral marginal zone were derived from
      varicose axons of more medially located Reelin-positive cells. Thus, the
      laterally located secreted Reelin product may normally prevent the preganglionic
      neurons from migrating too far medially. Based on the strong evolutionary
      conservation of Reelin expression and its postnatal detection, Reelin may have
      other important functions in addition to its role in neuronal migration.

PMID- 14648678
TI  - Calbindin-containing interneurons are a target for VIP-immunoreactive synapses in
      rat primary somatosensory cortex.
AB  - Inhibitory interneurons in cerebral cortex are morphologically and
      physiologically extremely heterogeneous. This greatly interferes with an
      understanding of their functions. Progress has been made by classifying these
      neurons with the aid of molecular markers, e.g., neuropeptides or calcium-binding
      proteins, which are reliably expressed by certain subpopulations. We have used
      this approach to demonstrate an output of a subpopulation of cortical
      interneurons which express vasoactive intestinal polypeptide (VIP). By double
      immunostaining and correlated light and electron microscopy, we show that
      calbindin (CB)-containing interneurons located in layers II-VI of rat barrel
      cortex are targets of symmetric VIP-immunoreactive synapses. All CB
      immunoreactive interneurons showed numerous contacts of VIP boutons on proximal
      and distal dendritic segments. A great majority of CB-immunoreactive interneurons
      (214/222) displayed such close appositions with VIP boutons on their soma as
      well. Quantification revealed that the number of VIP-immunoreactive boutons on CB
      immunoreactive somata and dendrites of specified order is comparable for the
      different cortical layers. In conclusion, all calbindin-containing cortical
      interneurons seem to be under direct influence of other GABAergic interneurons
      expressing the peptide VIP. An indirect functional consequence of this may be
      disinhibition of pyramidal cells, which are considered the major target of
      calbindin interneurons. However, since the examined types of interneurons are
      intricately embedded in networks of yet different interneurons, the outcome of
      these multiple inhibitory interactions is likely to be less simplistic. It may be
      related to the timing of pyramidal cell discharge within and across layers of
      cortical columns.

PMID- 14648679
TI  - Evidence for progression in frontal cortical pathology in late-stage Huntington's
      disease.
AB  - Atrophy of the cerebral cortex in Huntington's disease is regionally
      heterogeneous and progressive, involving the entire cerebral mantle in terminal
      stages. Here, two areas (9 and 46) of the dorsolateral prefrontal cortex were
      analyzed in 11 late-stage (grades 3 or 4) Huntington's diseased patients and 8
      normal control subjects. We used a 3-dimensional cell counting method to assess
      laminar cell density, number, and width. Reductions in overall cortical thickness
      in areas 9 (26%) and 46 (23%) were comparable. Area 9 exhibited loss of
      projection neurons in layers III (16%), V (31%), and VI (37%); these same layers
      were also reduced in width (25%, 34%, and 46%, respectively). In area 46,
      reductions in cortical width in layers II (18%) and VI (35%) were not accompanied
      by neuronal loss. Glial density was increased in deeper layers, reaching
      significance in layer VI (68%) of area 9 and in layer V (75%) of area 46; glial
      number was not altered. Thus, area 46 exhibited marked cortical thinning without
      apparent neuronal degeneration, whereas in area 9 neuronal loss was pronounced,
      consistent with an advanced phase of cortical pathology. Prominent involvement of
      corticothalamic neurons is discussed in the context of striatal loop circuitry
      and a possible pathologic cascade of cortical degeneration.

PMID- 14648680
TI  - Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co
      expressed in GABA neurons in the rat telencephalon.
AB  - Among all described serotonin (5-HT) receptors in mammals, the type three (5-HT3)
      is the only ligand-gated ion channel receptor for serotonin. By using double in
      situ hybridization histochemistry, we found co-expression of the functional 5
      HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor in
      neurons of the rat telencephalon. Double-labeled 5-HT3A/CB1 neurons were found in
      the anterior olfactory nucleus, superficial and deep layers of the cortex,
      hippocampal formation (hippocampus, dentate gyrus, subiculum, and entorhinal
      cortex) and amygdala. Analysis of the proportion of neurons co-expressing 5-HT3A
      and CB1 receptors in the cortex and amygdala showed that, depending on the brain
      region, 37-53% of all neurons expressing the 5-HT3A subunit also expressed CB1
      transcripts; 16-72% of the total population of neurons expressing CB1 mRNA co
      expressed the 5-HT3A subunit. By using a combination of double in situ
      hybridization and immunohistochemistry, we demonstrated that 5-HT3A/CB1
      expressing neurons contained the inhibitory neurotransmitter gamma-aminobutyric
      acid (GABA). These results imply that in distinct regions of the telencephalon,
      GABA neurons that react to cannabinoids may also be responsive to serotonin
      through 5-HT3 receptors. Cellular coexistence of 5-HT3A and CB1 transcripts in
      interneurons of the cortex, hippocampal formation, and amygdala suggest possible
      interactions between the cannabinoid and serotonergic systems at the level of
      GABA neurotransmission in brain areas involved in cognition, memory, and emotion.

PMID- 14648681
TI  - Temporal and spatial regulation of chondroitin sulfate, radial glial cells,
      growing commissural axons, and other hippocampal efferents in developing
      hamsters.
AB  - We investigated the time and space relationship between growth of hippocampal
      efferents, particularly those forming the hippocampal commissure, and expression
      of extracellular matrix components related to radial glial cells. Developing
      hamster brains from embryonic day (E) 13 to postnatal day (P) 7 had 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) crystals
      implanted into the hippocampus or were processed for fluorescent
      immunohistochemistry against chondroitin sulfate (CS) glycosaminoglycans and
      glial fibrillary acidic protein (GFAP). The first, pioneer fibers from the
      hippocampus were seen crossing the midline at E15 and arriving at the
      contralateral hippocampus 24-48 hours later (P1), followed closely by a thick
      front of growing fibers. Before E15, CS expression was preceded by septal fusion
      and was concomitant with formation of the commissural tract. On E15, CS
      expression formed a U-shaped border below the fimbria. From E15 to P3, CS became
      expressed between the hippocampal commissure and the third ventricle and at the
      caudal borders of the fornix columns. As the hippocampal commissure expanded, CS
      expression became gradually lighter to virtually disappear by P7. On E15 and P1,
      GFAP-positive radial glial cells were present caudal (but not rostral) to the
      commissure at the midline, partially overlapping CS expression. Similar cells
      were present dorsal to the fimbria, extending their processes perpendicularly
      over the growing axons. The data reveal that CS and radial glial cells form a
      tunnel surrounding the developing fimbria and a border at the midline caudal to
      the hippocampal commissure. It is suggested that these cellular and molecular
      borders play a role in guidance of hippocampal efferents.

PMID- 14648682
TI  - The temporal sequence of morphological and molecular changes in axotomized feline
      motoneurons leading to the formation of axons from the ends of dendrites.
AB  - At 8-12 weeks post axotomy, unusual distal processes (UDPs) with axon-like
      structural (uniform diameter, tortuous) and molecular (growth-associated protein
      [GAP]43, absence of microtubule-associated protein [MAP]2a/b immunoreactivity)
      features emerge from distal motoneuron dendrites (Rose et al. [2001] Eur J
      Neurosci 13:1166-1176). In this study, we determine the time course of molecular
      and morphological changes associated with the formation of axons from dendrites.
      Motoneurons innervating neck muscles in the adult cat were permanently axotomized
      for 2, 4, 20, or 35 weeks and intracellularly stained with Neurobiotin. Computer
      assisted reconstructions were used to map the location of MAP2a/b and GAP-43
      immunoreactivity. At 2 and 4 weeks post axotomy, all UDPs had short appendages,
      giving them an arboreal appearance. They were immunoreactive for GAP-43 and
      lacked immunostaining for MAP2a/b. Axon-like UDPs were not seen until 8-12 weeks
      post axotomy. By 20 and 35 weeks post axotomy, some axon-like UDPs acquired
      morphological features of axons with synaptic connections (right-angled
      branching, bouton-like specializations). GAP-43 immunoreactivity was not detected
      in any axotomized motoneurons by 20 weeks post axotomy, whereas all UDPs remained
      devoid of MAP2a/b immunoreactivity even at 35 weeks post axotomy. These molecular
      changes accompanied structural modifications to proximal regions of "dendrites"
      giving rise to UDPs. The distance from the ends of the UDPs to the soma did not
      change. Thus, all UDPs begin as simple, arboreal structures with molecular
      features of growing axons, but over a period of 35 weeks, some UDPs slowly
      acquire morphological and molecular features of motoneuron axons with synaptic
      connections. These results suggest a new modus operandi for axonal growth and the
      establishment of new synaptic connections after injury.

PMID- 14648683
TI  - Characterization of an amacrine cell type of the mammalian retina immunoreactive
      for vesicular glutamate transporter 3.
AB  - Immunocytochemical staining of vertical sections through rat, mouse, and macaque
      monkey retinae with antibodies against the vesicular glutamate transporter
      vesicular glutamate transporter 3 (vGluT3) showed a sparse population of amacrine
      cells. The labeled cells had similar appearances in the three species and
      probably represent homologous types. They were studied in detail in the rat
      retina. The thin varicose dendrites of vGluT3 amacrine cells formed a convoluted
      dendritic tree of approximately 100 microm in diameter that was bistratified in
      the center of the inner plexiform layer. The dendrites of vGluT3 cells were
      squeezed between the two strata of cholinergic dendrites. The density of vGluT3
      cells was measured in retinal wholemounts and increased from 200/mm2 in
      peripheral retina to 400/mm2 in central retina, accounting for about 1% of all
      amacrine cells in the rat retina. The vGluT3 cells had a two- to threefold
      dendritic overlap, and their cell bodies formed a regular mosaic, suggesting they
      represent a single type of amacrine cell. The vGluT3 amacrine cells expressed
      glycine and glycine transporter 1 (GlyT1) but not the vesicular glycine
      transporter (vesicular inhibitory amino acid transporter). They also expressed
      glutamate; hence, there is the possibility that, comparable to cholinergic
      amacrine cells, they are "dual transmitter" amacrine cells. The synaptic input of
      vGluT3 cells was studied by electron microscopy. They received input from bipolar
      cells at ribbon synapses and from other amacrine cells at conventional synapses.
      The types of bipolar cells possibly involved with vGluT3 cells were demonstrated
      by double labeling sections for vGluT3 and the calcium-binding protein CaB5. The
      axon terminals of type 3 and 5 bipolar cells costratified with vGluT3 dendrites,
      and it is possible that vGluT3 cells have ON and OFF light responses.

PMID- 14648684
TI  - Calcyon transcript expression in macaque brain.
AB  - The anatomical distribution of the transcript encoding calcyon, a 24 kDa membrane
      protein associated with coupling D1-like dopamine receptor activation to
      potentiated intracellular calcium release, was examined using in situ
      hybridization in the macaque brain. Calcyon mRNA is found to be abundantly
      distributed throughout the primate brain. In neocortex, moderately dense, diffuse
      signal is found in all areas, with increased intensity present in a superficial
      isodense band corresponding generally to cortical layers II and III. Increased
      intensity of signal is also seen in the pyramidal cell layers of medial
      prefrontal and anterior cingulate cortex. Calcyon mRNA is present abundantly in
      subcortical limbic areas such as the nucleus accumbens, septum, hypothalamus,
      amygdala, and hippocampus. Moderate calcyon transcript expression is seen in
      caudate and putamen, with lower levels in globus pallidus. Thalamic nuclei,
      including the reticular nucleus, express low to moderate levels. Very dense
      expression is noted in the substantia nigra pars compacta. Numerous brainstem
      regions express this transcript, notably monoaminergic nuclei including the locus
      coeruleus and dorsal raphe. The cerebellum has detectable levels of expression in
      both cortex and deep nuclei. Although calcyon is hypothesized as a means for D1
      like receptors to modulate "cross-talk" with other neurotransmitter receptor
      systems, it is notable that abundant calcyon transcript is detected in brain
      regions not associated with D1-like neurotransmission, particularly the
      substantia nigra pars compacta and other dopamine-synthesizing cell groups. A
      substantial proportion of this may relate to the reported association of calcyon
      with the D5 receptor, or in addition, may suggest that calcyon has a wider role
      as a regulator of intracellular signal transduction.

PMID- 14648685
TI  - Organization of axonal projections from the anterolateral area of the bed nuclei
      of the stria terminalis.
AB  - The anterolateral group of the bed nuclei of the stria terminalis (BSTalg)
      contains four distinct cell groups embedded within an undifferentiated
      anterolateral area (BSTal) that architectonically resembles a subjacent
      subcommissural zone (BSTsc). The overall distributions of axonal projections from
      various regions of the BSTal and from the BSTsc were determined with the
      Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracer method and found to
      be identical. The BSTal and BSTsc share dense bidirectional connections, and also
      project heavily within the BST to the rhomboid and fusiform nuclei and the
      anteroventral and anterodorsal areas. They project less densely to the
      juxtacapsular, oval, magnocellular, ventral, and interfascicular BST nuclei.
      Outside the BST, brain areas receiving strong to moderate inputs from the BSTal
      and BSTsc fall into several functional groups: somatomotor system (nucleus
      accumbens, substantia innominata, ventral tegmental area, and retrorubral area
      and adjacent midbrain reticular nucleus), central autonomic control system
      (central amygdalar nucleus, dorsal lateral hypothalamic area, ventrolateral
      periaqueductal gray, parabrachial nucleus, and nucleus of the solitary tract),
      neuroendocrine system (paraventricular and supraoptic nuclei, hypothalamic
      visceromotor pattern generator network), and thalamocortical feedback loops
      (midline, medial, and intralaminar nuclei). The results indicate that the BSTal
      and BSTsc are parts of the same cell group (dorsal and ventral to the anterior
      commissure), which plays a role in coordinating visceral and somatic motor
      responses (during ingestive behaviors, for example), especially in response to
      noxious stimuli (learned anorexia associated with noxious stimuli). BSTal
      projections are distinct from those of the adjacent juxtacapsular, oval,
      fusiform, and rhomboid nuclei.

PMID- 14648686
TI  - Dorsal striatopallidal system in anurans.
AB  - The dorsal striatopallidal system of tetrapods consists of the dorsal striatum
      (caudate-putamen in mammals) and the dorsal pallidum. Although the existence of
      striatal and pallidal structures has been well documented in anuran amphibians,
      the exact boundaries of these structures have so far been a matter of debate. To
      delineate precisely the dorsal striatopallidal system of anurans, we used
      quantitative analysis of leucine-enkephalin immunohistochemistry (in Bombina
      orientalis, Discoglossus pictus, Xenopus laevis, and Hyla versicolor), retrograde
      neurobiotin tracing studies (injections in the central and ventromedial thalamic
      nuclei in H. versicolor), and double-labeling tracing studies (injections in the
      lateral forebrain bundle and the caudal striatum in B. orientalis).
      Immunohistochemistry revealed that enkephalin-positive neurons are located mainly
      in the rostral and intermediate striatum. Neurobiotin tracing studies
      demonstrated that neurons projecting to the central and ventromedial thalamic
      nuclei are found in the intermediate and caudal striatum. Double-labeling studies
      revealed that the population of neurons in the rostral and intermediate striatum
      innervating the caudal striatum is separated from neurons projecting into the
      lateral forebrain bundle. Neurons that project to both the caudal striatum and
      the lateral forebrain bundle are found only in the dorsal part of the
      intermediate striatum. Taken together, our results suggest that the rostral
      striatum of anurans is homologous to the striatum proper of mammals, whereas the
      caudal striatum is comparable to the dorsal pallidum. The intermediate striatum
      represents a transition area between the two structures.

PMID- 14648688
TI  - Chemical neuroanatomy of the fly's movement detection pathway.
AB  - In Diptera, subsets of small retinotopic neurons provide a discrete channel from
      achromatic photoreceptors to large motion-sensitive neurons in the lobula
      complex. This pathway is distinguished by specific affinities of its neurons to
      antisera raised against glutamate, aspartate, gamma-aminobutyric acid (GABA),
      choline acetyltransferase (ChAT), and a N-methyl-D-aspartate type 1 receptor
      protein (NMDAR1). Large type 2 monopolar cells (L2) and type 1 amacrine cells,
      which in the external plexiform layer are postsynaptic to the achromatic
      photoreceptors R1-R6, express glutamate immunoreactivity as do directionally
      selective motion-sensitive tangential neurons of the lobula plate. L2 monopolar
      cells ending in the medulla are accompanied by terminals of a second efferent
      neuron T1, the dendrites of which match NMDAR1-immunoreactive profiles in the
      lamina. L2 and T1 endings visit ChAT and GABA-immunoreactive relays
      (transmedullary neurons) that terminate from the medulla in a special layer of
      the lobula containing the dendrites of directionally selective retinotopic T5
      cells. T5 cells supply directionally selective wide-field neurons in the lobula
      plate. The present results suggest a circuit in which initial motion detection
      relies on interactions among amacrines and T1, and the subsequent convergence of
      T1 and L2 at transmedullary cell dendrites. Convergence of ChAT-immunoreactive
      and GABA-immunoreactive transmedullary neurons at T5 dendrites in the lobula, and
      the presence there of local GABA-immunoreactive interneurons, are suggested to
      provide excitatory and inhibitory elements for the computation of motion
      direction. A comparable immunocytological organization of aspartate- and
      glutamate-immunoreactive neurons in honeybees and cockroaches further suggests
      that neural arrangements providing directional motion vision in flies may have
      early evolutionary origins.

PMID- 14648689
TI  - A comparative reappraisal of projections from the superficial laminae of the
      dorsal horn in the rat: the forebrain.
AB  - Projections to the forebrain from lamina I of spinal and trigeminal dorsal horn
      were labeled anterogradely with Phaseolus vulgaris-leucoagglutinin (PHA-L) and/or
      tetramethylrhodamine-dextran (RHO-D) injected microiontophoretically. Injections
      restricted to superficial laminae (I/II) of dorsal horn were used primarily. For
      comparison, injections were also made in deep cervical laminae. Spinal and
      trigeminal lamina I neurons project extensively to restricted portions of the
      ventral posterolateral and posteromedial (VPL/VPM), and the posterior group (Po)
      thalamic nuclei. Lamina I also projects to the triangular posterior (PoT) and the
      ventral posterior parvicellular (VPPC) thalamic nuclei but only very slightly to
      the extrathalamic forebrain. Furthermore, the lateral spinal (LS) nucleus, and to
      a lesser extent lamina I, project to the mediodorsal thalamic nucleus. In
      contrast to lamina I, deep spinal laminae project primarily to the central
      lateral thalamic nucleus (CL) and only weakly to the remaining thalamus, except
      for a medium projection to the PoT. Furthermore, the deep laminae project
      substantially to the globus pallidus and the substantia innominata and more
      weakly to the amygdala and the hypothalamus. Double-labeling experiments reveal
      that spinal and trigeminal lamina I project densely to distinct and restricted
      portions of VPL/VPM, Po, and VPPC thalamic nuclei, whereas projections to the PoT
      appeared to be convergent. In conclusion, these experiments indicate very
      different patterns of projection for lamina I versus deep laminae (III-X). Lamina
      I projects strongly onto relay thalamic nuclei and thus would have a primary role
      in sensory discriminative aspects of pain. The deep laminae project densely to
      the CL and more diffusely to other forebrain targets, suggesting roles in motor
      and alertness components of pain.

PMID- 14648690
TI  - Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the
      emergence of low intracellular chloride.
AB  - Fast synaptic inhibition in the adult central nervous system (CNS) is mediated by
      GABA and glycine. During early development GABA acts as an excitatory
      neurotransmitter, which is deemed to be important for the maturation of the CNS.
      During development GABAergic responses undergo a switch from excitatory to
      inhibitory. This switch is correlated with upregulation of KCC2, the neuronal
      isoform of the potassium-chloride cotransporter family. KCC2 lowers the
      intraneuronal chloride concentration below its electrochemical equilibrium. KCC2
      activity is thought to depend on phosphorylation by endogenous tyrosine kinases.
      Here, we analyzed the expression pattern of KCC2 during murine embryonic and
      postnatal development by in situ hybridization and Western blot analysis. KCC2
      expression paralleled neuronal differentiation and preceded the decline of the
      GABA reversal potential (EGABA) in spinal cord motoneurons and hippocampal
      pyramidal cells. The adult inhibitory response to GABA was established earlier in
      the spinal cord than in the hippocampus. Phosphorylated KCC2 protein was already
      present early in development when the functional GABA switch had not yet
      occurred. Thus, tyrosine-phosphorylation seems to be less important than the
      transcriptional upregulation of KCC2.

PMID- 14648691
TI  - Centrifugal visual system of Crocodylus niloticus: a hodological, histochemical,
      and immunocytochemical study.
AB  - The retinopetal neurons of Crocodylus niloticus were visualized by retrograde
      transport of rhodamine beta-isothiocyanate or Fast Blue administered by
      intraocular injection. Approximately 6,000 in number, these neurons are
      distributed in seven regions extending from the mesencephalic tegmentum to the
      rostral rhombencephalon, approximately 70% being located contralaterally to the
      injected eye. None of the centrifugal neurons projects to both retinae. The
      retinopetal neurons are located in rostrocaudal sequence in seven regions: the
      formatio reticularis lateralis mesencephali, the substantia nigra, the griseum
      centralis tectalis, the nucleus subcoeruleus dorsalis, the nucleus isthmi
      parvocellularis, the locus coeruleus, and the commissura nervi trochlearis. The
      greatest number of cells (approximately 93%) is found in the nucleus subcoeruleus
      dorsalis. The majority are multipolar or bipolar in shape and resemble the
      ectopic centrifugal visual neurons of birds, although a small number of monopolar
      neurons resembling those of the avian isthmo-optic nucleus may also be observed.
      A few retinopetal neurons in the griseum centralis tectalis were tyrosine
      hydroxylase (TH) immunoreactive. Moreover, in the nuclei subcoeruleus dorsalis
      and isthmi parvocellularis, both ipsilaterally and contralaterally, approximately
      one retinopetal neuron in three (35%) was immunoreactive to nitric oxide synthase
      (NOS), and a slightly higher proportion (38%) of retinopetal neurons were
      immunoreactive for choline acetyltransferase (ChAT). Some of them contained
      colocalized ChAT and NOS/reduced nicotinamide adenine dinucleotide phosphate
      diaphorase. Fibers immunoreactive to TH, serotonin (5-HT), neuropeptide Y (NPY),
      or Phe-Met-Arg-Phe-amide (FMRF-amide) were frequently observed to make intimate
      contact with rhodamine-labeled retinopetal neurons. These findings are discussed
      in relation to previous results obtained in other reptilian species and in birds.

PMID- 14648692
TI  - Differences in the expression of AMPA and NMDA receptors between axospinous
      perforated and nonperforated synapses are related to the configuration and size
      of postsynaptic densities.
AB  - Axospinous synapses are traditionally divided according to postsynaptic density
      (PSD) configuration into a perforated subtype characterized by a complex-shaped
      PSD and nonperforated subtype exhibiting a simple-shaped, disc-like PSD. It has
      been hypothesized that perforated synapses are especially important for synaptic
      plasticity because they have a higher efficacy of impulse transmission. The aim
      of the present study was to test this hypothesis. The number of postsynaptic AMPA
      receptors (AMPARs) is widely regarded as the major determinant of synaptic
      efficacy. Therefore, the expression of AMPARs was evaluated in the two synaptic
      subtypes and compared with that of NMDA receptors (NMDARs). Postembedding
      immunogold electron microscopy was used to quantify the immunoreactivity
      following single labeling of AMPARs or NMDARs in serial sections through the CA1
      stratum radiatum of adult rats. The results showed that all perforated synapses
      examined were immunopositive for AMPARs. In contrast, only a proportion of
      nonperforated synapses (64% on average) contained immunogold particles for
      AMPARs. The number of immunogold particles for AMPARs was markedly and
      significantly higher in perforated synapses than in immunopositive nonperforated
      synapses. Although all synapses of both subtypes were NMDAR immunopositive
      perforated synapses contained significantly more immunogold particles for NMDARs
      than nonperforated ones. Multivariate analysis of variance revealed that the mode
      of AMPAR and NMDAR expression is related to the complexity of PSD configuration,
      not only to PSD size. These findings support the notion that perforated synapses
      may evoke larger postsynaptic responses relative to nonperforated synapses and,
      hence, contribute to an enhancement of synaptic transmission associated with some
      forms of synaptic plasticity.

PMID- 14648693
TI  - Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex
      express GAP-43 mRNA in the adult rat.
AB  - The expression of a presynaptic phosphoprotein, growth-associated protein (GAP)
      43, is associated with synaptogenesis during development and synaptic remodeling
      in the adult. This study examined GAP-43 mRNA expression and distribution in
      primary and secondary areas of visual, auditory, and somatosensory cortex of the
      adult rat, by in situ hybridization with a digoxigenin-coupled mRNA probe,
      focusing particularly on the corticothalamic cells in layers 5 and 6. In the six
      cortical areas studied, GAP-43 mRNA was expressed predominantly in layers 5 and 6
      and was greater in secondary than primary areas. There were densely labeled cells
      in layers 5 and 6 of all areas, which showed a restricted sublaminar distribution
      in primary areas and more even distribution in secondary areas. Combining
      retrograde transport of rhodamine beads with in situ hybridization in visual and
      auditory cortex showed that corticothalamic cells in layers 5 and 6 express GAP
      43 mRNA. There are more of these GAP-43 mRNA positive corticothalamic cells in
      layer 5 of secondary areas than in primary areas. The evidence suggests that in
      the adult rat, plasticity related to GAP-43 is present in primary and secondary
      sensory cortex and more so in secondary areas.

PMID- 14648694
TI  - Correlation of electrophysiological and morphological characteristics of enteric
      neurons in the mouse colon.
AB  - We report on the first correlative study of the electrophysiological properties,
      shapes, and projections of enteric neurons in the mouse. Neurons in the myenteric
      plexus of the mouse colon were impaled with microelectrodes containing biocytin,
      their passive and active electrophysiological properties determined, and their
      responses to activation of synaptic inputs investigated. Biocytin, injected into
      the neurons from which recordings were made, was converted to an optically dense
      product and used to determine the shapes of neurons. By electrophysiological
      properties, almost all neurons belonged to one of two classes, AH neurons or S
      neurons. AH neurons had a biphasic repolarization of the action potential, and
      slow afterhyperpolarizing potentials usually followed the action potentials. S
      neurons had monophasic repolarizations, no slow afterhyperpolarization, and fast
      excitatory postsynaptic potentials in response to fibre tract stimulation. By
      shape, neurons were divided into Dogiel type II (28/136 neurons) and uniaxonal
      neurons. Dogiel type II neurons had large, smooth-surfaced cell bodies and
      several long processes that supplied branches within myenteric ganglia. All
      Dogiel type II neurons had AH electrophysiology; conversely, most AH neurons had
      Dogiel type II morphology. The majority of uniaxonal neurons had lamellar
      dendrites, i.e., Dogiel type I morphology. They projected to the circular muscle
      (circular muscle motor neurons), to the longitudinal muscle (longitudinal muscle
      motor neurons), and to other myenteric ganglia (interneurons) and in some cases
      could not be traced to target cells. All S neurons were uniaxonal. A small
      proportion of uniaxonal neurons (3/70) had AH electrophysiology. Fast excitatory
      synaptic potentials were only recorded from uniaxonal neurons and were in most
      cases blocked by nicotinic receptor antagonists. A small component of fast
      excitatory transmission in some neurons was antagonized by the purine receptor
      antagonist PPADS. Slow excitatory postsynaptic potentials were observed in both
      AH and S neurons. Slow inhibitory postsynaptic potentials were recorded from S
      neurons. We conclude that the major classes of neurons are Dogiel type II neurons
      with AH electrophysiological properties and Dogiel type I neurons with S
      electrophysiological properties. The S/Dogiel type I neurons include circular
      muscle motor neurons, longitudinal muscle motor neurons, and interneurons.

PMID- 14648695
TI  - Correlation of expression of the actin filament-bundling protein espin with
      stereociliary bundle formation in the developing inner ear.
AB  - The vertebrate hair cell is named for its stereociliary bundle or hair bundle
      that protrudes from the cell's apical surface. Hair bundles mediate
      mechanosensitivity, and their highly organized structure plays a critical role in
      mechanoelectrical transduction and amplification. The prototypical hair bundle is
      composed of individual stereocilia, 50-300 in number, depending on the animal
      species and on the type of hair cell. The assembly of stereocilia, in particular,
      the formation during development of individual rows of stereocilia with
      descending length, has been analyzed in great morphological detail. Electron
      microscopic studies have demonstrated that stereocilia are filled with actin
      filaments that are rigidly cross-linked. The growth of individual rows of
      stereocilia is associated with the addition of actin filaments and with
      progressively increasing numbers of cross-bridges between actin filaments.
      Recently, a mutation in the actin filament-bundling protein espin has been shown
      to underlie hair bundle degeneration in the deaf jerker mouse, subsequently
      leading to deafness. Our study was undertaken to investigate the appearance and
      developmental expression of espin in chicken inner ear sensory epithelia. We
      found that the onset of espin expression correlates with the initiation and
      growth of stereocilia bundles in vestibular and cochlear hair cells. Intense
      espin immunolabeling of stereocilia was colocalized with actin filament staining
      in all types of hair cells at all developmental stages and in adult animals. Our
      analysis of espin as a molecular marker for actin filament cross-links in
      stereocilia is in full accordance with previous morphological studies and
      implicates espin as an important structural component of hair bundles from
      initiation of bundle assembly to mature chicken hair cells.

PMID- 14648696
TI  - Distribution of tyrosine hydroxylase, dopamine, and serotonin in the central
      nervous system of amphioxus (Branchiostoma lanceolatum): implications for the
      evolution of catecholamine systems in vertebrates.
AB  - To investigate the evolutionary transition that has shaped the catecholaminergic
      systems of vertebrates, the organization of catecholamine-synthesizing neurons
      and the nature of the catecholamines were examined in the central nervous system
      of adult amphioxus (Branchiostoma lanceolatum), a cephalochordate. We isolated a
      gene transcript encoding tyrosine hydroxylase (TH), the limiting enzyme of
      catecholamine biosynthesis, and studied its distribution together with that of
      dopamine and serotonin. Dopamine and TH are found in the same neurons of which
      they are three separate populations. Two are located in the anterior brain, the
      first being dorsal and lying in a row and the second being more posterior and
      lateral. A third population comprising a few dorsal commissural neurons was found
      in the posterior brain. The anterior dopaminergic cells innervate the ventral
      commissure of the cephalic vesicle, the hindbrain, and the spinal cord. A
      serotonin-containing cell group is located in the same plane as the second
      dopaminergic cell population but is more caudal, marking the probable transition
      between anterior brain and hindbrain, as deduced from gene expression patterns.
      The overall distribution of dopaminergic and serotoninergic systems is similar in
      amphioxus and vertebrate central nervous system and could be an ancestral
      character of chordates. As assayed by high-performance liquid chromatography and
      electrochemical detection, significant amounts of dopamine and octopamine, but
      not of noradrenaline, are present in amphioxus head. This finding is consistent
      with data obtained from most prostomian species. We conclude that the
      noradrenergic system is probably an innovation of vertebrates that appeared along
      with the neural crest and specific hindbrain nuclei.

PMID- 14648697
TI  - Cervical cancer control, priorities and new directions.
AB  - Cervical cancer is caused by infection with a range of high risk "oncogenic"
      human papillomavirus (HPV) types, and it is now accepted that >99% of cervical
      cancer is initiated by HPV infection. The estimated lifetime risk of cervical
      cancer is nevertheless relatively low (less than 1 in 20 for most community based
      studies). Although sensitivity and specificity of the available diagnostic
      techniques are suboptimal, screening for persistent HPV infection is effective in
      reducing the incidence of cervical cancer. Infection can be detected by molecular
      techniques or by cytological examination of exfoliated cervical cells. Persistent
      infection is the single best predictor of risk of cervical cancer. The latest
      findings of HPV and cervical cancer research need to be widely disseminated to
      the scientific and medical societies that are updating screening and management
      protocols, public health professionals, and to women and clinicians. This report
      reviews current evidence, clinical implications and directions for further
      research in the prevention, control and management of cervical cancer. We report
      the conclusions of the Experts' Meeting at the EUROGIN 2003 conference.

PMID- 14648698
TI  - Molecular mechanisms underlying IGF-I-induced attenuation of the growth
      inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells.
AB  - The clinical usefulness of trastuzumab (Herceptin; Genentech, San Francisco, CA)
      in breast cancer treatment is limited by the rapid development of resistance. We
      previously reported that IGF-I signaling confers resistance to the growth
      inhibitory actions of trastuzumab in a model system, but the underlying molecular
      mechanism remains unknown. We used SKBR3/neo cells (expressing few IGF-I
      receptors) and SKBR3/IGF-IR cells (overexpressing IGF-I receptor) as our
      experimental model. IGF-I antagonized the trastuzumab-induced increase in the
      level of the Cdk inhibitor p27(Kip1). This resulted in decreased association of
      p27(Kip1) with Cdk2, restoration of Cdk2 activity and attenuation of cell-cycle
      arrest in G(1) phase, all of which had been induced by trastuzumab treatment in
      SKBR3/IGF-IR cells. We also found that the decrease in p27(Kip1) induced by IGF-I
      was accompanied by an increase in expression of Skp2, which is a ubiquitin ligase
      for p27(Kip1), and by increased Skp2 association with p27(Kip1). A specific
      proteasome inhibitor (LLnL) completely blocked the ability of IGF-I to reduce the
      p27(Kip1) protein level, while IGF-I increased p27(Kip1) ubiquitination. This
      suggests that the action of IGF-I in conferring resistance to trastuzumab
      involves targeting of p27(Kip1) to the ubiquitin/proteasome degradation
      machinery. Finally, specific inhibitors of MAPK and PI3K suggest that the IGF-I
      mediated reduction in p27(Kip1) protein level by increased degradation
      predominantly involves the PI3K pathway. Our results provide an example of
      resistance to an antineoplastic therapy that targets one tyrosine kinase receptor
      by increased signal transduction through an alternative pathway in a complex
      regulatory network.

PMID- 14648699
TI  - Human agmatinase is diminished in the clear cell type of renal cell carcinoma.
AB  - The proteome of RCC was analyzed by 2D PAGE to search for tumor-associated
      proteins. Agmatinase, which hydrolyzes agmatine to putrescine and urea, was
      identified by mass spectrometry and database searches and shown to be
      downregulated in tumor cells. Additionally, RT-PCR and Northern blot analyses
      demonstrated a clearly decreased amount of agmatinase mRNA in tumor cells. The
      differential expression of agmatinase mRNA was confirmed at the protein level.
      Western blot analysis showed almost no detectable agmatinase protein in tumor
      cells compared to corresponding normal renal tissue. Agmatinase mRNA is most
      abundant in human liver and kidney but expressed to a lesser extent in several
      other tissues, including skeletal muscle and small intestine. The human
      agmatinase gene encodes a 352-residue protein with a putative mitochondrial
      targeting sequence at the N-terminus. Using transfection and immunohistochemical
      studies, we show that agmatinase is localized in the mitochondria.
      Immunohistochemical studies revealed that agmatinase in the normal kidney is
      restricted to tubulus epithelial cells, while in tumors staining was low and
      heterogeneous. Thus, expression of human agmatinase is altered in RCC. We discuss
      the consequences of these findings in terms of polyamine, NO metabolism and
      macrophage function.

PMID- 14648700
TI  - Basement membrane proteins promote progression of intraepithelial neoplasia in 3
      dimensional models of human stratified epithelium.
AB  - We have developed novel 3-dimensional in vitro and in vivo tissue models that
      mimic premalignant disease of human stratified epithelium in order to analyze the
      stromal contribution of extracellular matrix and basement membrane proteins to
      the progression of intraepithelial neoplasia. Three-dimensional, organotypic
      cultures were grown either on a de-epidermalized human dermis with pre-existing
      basement membrane components on its surface (AlloDerm), on a Type I collagen gel
      that lacked basement membrane proteins or on polycarbonate membranes coated with
      purified extracellular matrix proteins. When tumor cells (HaCaT-II4) were mixed
      with normal keratinocytes (4:1/normals:HaCaT-II4), tumor cells selectively
      attached, persisted and proliferated at the dermal-epidermal interface in vitro
      and generated dysplastic tissues when transplanted to nude mice only when grown
      in the presence of the AlloDerm substrate. This stromal interface was permissive
      for tumor cell attachment due to the rapid assembly of structured basement
      membrane. When tumor cells were mixed with normal keratinocytes and grown on
      polycarbonate membranes coated with individual extracellular matrix or basement
      membrane components, selective attachment and significant intraepithelial
      expansion occurred only on laminin 1 and Type IV collagen-coated membranes. This
      preferential adhesion of tumor cells restricted the synthesis of laminin 5 to
      basal cells where it was deposited in a polarized distribution. Western blot
      analysis revealed that tumor cell attachment was not due to differences in the
      synthesis or processing of laminin 5. Thus, intraepithelial progression towards
      premalignant disease is dependent on the selective adhesion of cells with
      malignant potential to basement membrane proteins that provide a permissive
      template for their persistence and expansion.

PMID- 14648701
TI  - Contribution of MEK/MAPK and PI3-K signaling pathway to the malignant behavior of
      Ewing's sarcoma cells: therapeutic prospects.
AB  - Insulin-like growth factor receptor I (IGF-I)-mediated circuit is a major
      autocrine loop for Ewing's sarcoma (ES) cells and appears to be particularly
      important in the pathogenesis of this tumor. In this study, we analyzed the
      contribution of the 2 major pathways of the intracellular IGF-IR signaling
      cascade to the overall effects elicited by IGF-I in ES. Both the mitogen
      activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3-K)
      signaling pathways appeared to be constitutively activated in ES, likely due to
      the presence of the IGF-IR-mediated autocrine loop. We demonstrated that both
      MEK/MAPK (PD98059 or U0126) and PI3-K inhibitors (LY294002) profoundly impaired
      ES cell growth in monolayer and soft agar basal conditions. Both PD98059 and
      LY294002 inhibited ES cell cycle progression by inducing G1 blockage, whereas
      only LY294002 significantly affected the survival of ES cells. Exogenous IGF-I
      completely reverted LY294002-induced growth inhibition by abrogating
      antiproliferative and proapoptotic effects of the PI3-K inhibitor. By contrast,
      IGF-I could not rescue cells from growth inhibition induced by PD98059. MEK/MAPK
      blockade also significantly reduced the migratory ability of ES cells, both in
      basal and IGF-I-induced conditions, and increased chemosensitivity to
      doxorubicin, a leader drug in the treatment of ES patients. Our findings
      therefore identify MAPK pathway as a promising target for pharmacologic
      intervention in ES.

PMID- 14648702
TI  - Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer
      cells.
AB  - Vitamin D and its analogues are potent regulators of cell growth and
      differentiation both in vivo and in vitro. We studied the effects of 25
      hydroxyvitamin D(3) [25(OH)D(3)], 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]
      and vitamin D analogue, EB 1089, on the growth of a human ovarian cancer cell
      line, OVCAR-3. We also studied the expression of vitamin D metabolising enzymes
      24-hydroxylase (24OHase) and 1alpha-hydroxylase (1alphaOHase). Our results showed
      that high concentrations (10 and 100 nM) of 1,25(OH)(2)D(3) inhibited a cell
      proliferation, whereas low concentration (0.1 nM) stimulated growth of the OVCAR
      3 cells. In the concentration range of 10-500 nM a prohormone, 25(OH)D(3),
      stimulated growth. An amount of 1 nM EB 1089 and 100 nM 1,25(OH)(2)D(3) inhibited
      growth with an equal magnitude. The expression of 24OHase was strongly induced by
      1,25(OH)(2)D(3) and EB 1089 in OVCAR-3 cells, and analysis of vitamin D
      metabolites showed the functionality of 24OHase. An inhibition of 24OHase
      activity with a novel 24OHase inhibitor enhanced growth-inhibiting effects of
      1,25(OH)(2)D(3) and suppressed the growth stimulation of 100 nM 25(OH)D(3). We
      also report the expression of a vitamin D activating enzyme, 1alphaOHase, in 7
      ovarian cancer cell lines. The production of 1,25(OH)(2)D(3) in OVCAR-3 cells was
      low, possibly due to an extensive activity of 24OHase or a low 1alphaOHase
      activity. These results suggest that in ovarian cancer cells vitamin D
      metabolizing enzymes might play a key role in modulating the growth response to
      vitamin D. The possible mitogenic effects of vitamin D should be considered when
      evaluating treatment of ovarian cancer with vitamin D.

PMID- 14648703
TI  - Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids.
AB  - Members of the claudin family together with occludin are the major constituents
      of the tight junction (TJ) complex. The human homologue of the murine CLDN1,
      previously called SEMP1, was identified by differential expression analysis, and
      the CLDN1 mRNA was found to be downregulated or completely lost in human breast
      cancer cells in vitro. Retroviral-induced CLDN1 reexpression in breast cancer
      cells results in plasma membrane homing of the protein and reconstitution of
      paracellular flux inhibition, which is not dependent on the presence of occludin
      protein. In this report, we investigated the physiologic role of CLDN1 in CLDN1
      transduced MDA-MB 361 breast tumor cells in adherent 2D and suspension 3D
      spheroid cell cultures. Retroviral-transduced bulk cultures were FACS-sorted to
      enrich for 100% CLDN1-positive clonal derivatives with similar expression levels
      of CLDN1 mRNA and protein. There was no difference in proliferation and cell
      death characteristics in 2D adherent cell cultures of CLDN1-positive compared to
      control CLDN1-negative and mock-transduced cell cultures. In contrast, the
      majority of the CLDN1-transduced derivatives displayed a significant elevation of
      apoptosis that became evident as early as 2 days after 3D spheroid culture onset.
      This elevated apoptosis was independent of the volume of established spheroids.
      The cellular immunofluorescence analysis of CLDN1 protein expression in
      transduced bulk cultures revealed a CLDN1-positive subfraction with a
      heterogeneous pattern of membrane and cytosolic immunostaining. In the clonal MDA
      MB 361 CLDN1-positive cultures, we found that a more prominent cell membrane
      localization correlated with a pronounced increase of apoptosis in tumor
      spheroids. In parallel, inhibition of the paracellular flux rate was observed.
      These findings support a potential role of the TJ protein CLDN1 in restricting
      nutrient and growth factor supplies in breast cancer cells, and they indicate
      that the loss of the cell membrane localization of the TJ protein CLDN1 in
      carcinomas may be a crucial step during tumor progression.

PMID- 14648704
TI  - PGE2-mediated upregulation of iNOS in murine breast cancer cells through the
      activation of EP4 receptors.
AB  - We report here that endogenous prostaglandin E(2) (PGE(2)) resulting from
      cyclooxygenase (COX)-2 expression in a highly metastatic murine breast cancer
      cell line C3L5 upregulates IFN-gamma + LPS-induced nitric oxide (NO) synthase
      (iNOS) expression and NO production. This action of PGE(2) is mediated through
      the EP(4) receptor in a cAMP-dependent manner. Both nonselective and selective
      COX-2 inhibitors suppressed IFN-gamma + LPS-induced NO production, which was
      largely restored by exogenous PGE(2) or EP(4) receptor agonist PGE(1) alcohol.
      EP(4) antagonist AH-23848B inhibited NO production with a concomitant
      downregulation of iNOS mRNA in IFN-gamma + LPS-stimulated cells. cAMP dependence
      of NO production by cells under inducible conditions was demonstrated by the use
      of known modulators of intracellular cAMP. Since both COX-2 and iNOS are
      implicated in breast cancer progression, our findings of EP(4) receptor-mediated
      upregulation of iNOS in COX-2-expressing breast cancer cells suggest that
      blocking COX-2 and/or EP(4) may provide a simple therapeutic modality in this
      tumor model.

PMID- 14648705
TI  - CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells
      signal proliferation and survival.
AB  - CD137, a member of the tumor necrosis factor receptor family, provides expansion
      and survival signal to T cells. Its ligand, CD137L, in addition to its ability to
      costimulate T cells, signals back into antigen presenting cells promoting their
      activation and differentiation. Recently, CD137 has been proposed as a
      therapeutic target to improve and sustain anticancer immune response. Several
      activated T leukemia and B lymphoma cell lines expressed CD137 or CD137L,
      respectively, and soluble CD137L has been found in sera of leukemia patients.
      However, the functionality and role of these costimulatory molecules in
      hematologic malignancies are until now unknown. Interestingly, we observed
      constitutive CD137 and CD137L coexpression on both human T and B leukemia cell
      lines. The constitutive CD137 expression on unstimulated T or B leukemia cells
      presents some differences compared to CD137 expressed on PMA/ionomycin-activated
      T leukemia cells. Surprisingly, in spite of the low expression level, both tumor
      CD137 and CD137L molecules signaled in T and B leukemia cells inducing
      proliferation and prolonging survival. In addition, CD137/CD137L system ligation
      opposed the anticancer drug cytotoxic effects, reducing the apoptotic DNA
      fragmentation and stimulating proliferation of doxorubicin-escaped leukemia
      cells. Although the role of leukemia CD137/CD137L system in vivo is unknown,
      these data suggest that these costimulatory molecules might confer an advantage
      to hematologic tumors promoting survival, sustaining cellular growth and
      contributing to drug resistance.

PMID- 14648706
TI  - Polyglutamine repeat length in the AIB1 gene modifies breast cancer
      susceptibility in BRCA1 carriers.
AB  - Variation in the penetrance estimates for BRCA1 and BRCA2 mutation carriers
      suggests that other factors may modify cancer risk from specific mutations. One
      possible mechanism is an epigenetic effect of polymorphisms in other genes. Genes
      involved in hormonal signal transduction are possible candidates. The AIB1 gene,
      an estrogen receptor (ER) coactivator, is frequently amplified in breast and
      ovarian tumors. Variation of a CAG repeat length has been reported within this
      gene that encodes a polyglutamine repeat in the C-terminus of the protein. Three
      hundred eleven BRCA1/2 mutation carriers (257 were of Ashkenazi origin) were
      genotyped for the AIB1 polyglutamine repeat. Relative risks (RR) were estimated
      using a maximum likelihood approach. The estimated breast cancer (BC) RR per
      average repeat length adjusted for population type (Ashkenazi vs. non-Ashkenazi)
      was 1.15 (95% CI = 1.02-1.30; p = 0.01) for BRCA1/2 carriers, and 1.25 (95% CI =
      1.09-1.42; p = 0.001) when analysis was restricted to BRCA1 carriers. RR of BC
      was 1.17 (95% CI = 0.91-1.74), for individuals with 2 alleles >/=29 polyglutamine
      repeats and 0.78 (95% CI = 0.50-1.16) for those with at least 1 allele of </=26
      repeats, compared to individuals with the common genotypes 28;28, 28;29 or 28;30.
      The corresponding BC RR in BRCA1 mutation carriers was 0.55 (95% CI = 0.34-0.90)
      and 1.29 (95% CI = 0.85-1.96) in those with </=26 and >/=29 repeats respectively
      (p = 0.025). These results indicate significant association of the risk for BC in
      carriers of BRCA1 mutations with the polyglutamine chain of the AIB1 gene. Longer
      repeat length correlates with elevated risk, whereas in carriers of a shorter
      AIB1 allele BC risk was reduced. The AIB1 polyglutamine length did not affect BC
      risk among BRCA2 mutation carriers.

PMID- 14648707
TI  - Intake of beer inhibits azoxymethane-induced colonic carcinogenesis in male
      Fischer 344 rats.
AB  - Modulatory effects of beer consumption on azoxymethane (AOM)-induced rat colonic
      carcinogenesis in male Fischer 344 rats were investigated. Single cell gel
      electrophoresis assay indicated that DNA damage of colonocytes, induced by a
      single AOM injection (15 mg/kg body weight), was significantly reduced in rats
      fed beer or malt extract for 2 weeks. Examination of aberrant crypt foci (ACF)
      formation in colonic mucosa, induced by AOM (15 mg/kg body weight; twice weekly),
      revealed that feeding of beer during the whole experimental period of 5 weeks
      significantly reduced the number of ACF by 35%. In the post-initiation protocol,
      a reduction in ACF formation by 26% was not significant. The efficacy in
      inhibition of ACF formation varied with the brand of beer. ACF formation was
      significantly reduced in rats treated with freeze-dried beer (FD Beer), but not
      with ethanol, suggesting that nonvolatile components of beer are responsible for
      the reduction. Significant suppression of ACF formation was observed in groups
      treated with hot water extract of malt, especially with extracts of colored
      malts, although no reduction was observed by feeding with hops extract. A long
      term experiment of 42 weeks indicated that intake of beer decreased tumor
      incidence by 22% and decreased the number of neoplastic lesions, including
      adenocarcinomas and adenomas, by 44%. These results suggest that components of
      beer have chemopreventive effects on colonic carcinogenesis induced by AOM and
      that intake of beer may contribute to a reduction in the risk of cancer
      susceptibility.

PMID- 14648708
TI  - Quantification of cytokeratin 20, carcinoembryonic antigen and guanylyl cyclase C
      mRNA levels in lymph nodes may not predict treatment failure in colorectal cancer
      patients.
AB  - Conventional histopathologic staging of primary colorectal cancers does not allow
      accurate prognostic stratification within a given tumour stage. Therefore, PCR
      based assays are increasingly used to try to predict more accurately the
      likelihood of disease progression for the individual patient. Real-time reverse
      transcription PCR (RT-PCR) assays were used to detect and quantitate cytokeratin
      20 (ck20), carcinoembryonic antigen (CEA) and guanylyl cyclase C (GCC) mRNA in
      149 lymph nodes (LN) from 17 patients with benign disease and 302 LN from 42
      patients with colorectal cancer who had curative (R0) resections. None of the
      markers were specific, with ck20, CEA and GCC mRNA detected in 47%, 89% and 13%
      of 149 LN, respectively, from patients with benign disease. The sensitivity of
      all 3 markers was very high, with mRNA detected in 93%, 100% and 97% of 30
      histologically involved LN, respectively. There was significant overlap in the
      mRNA levels of all 3 markers between histologically involved and uninvolved LN.
      There was no association between mRNA levels and distant recurrence (median
      follow-up: 3.94 years, range 3.35-5.12). We conclude that the use of molecular
      techniques to detect occult disease in LN may suffer from the same limitations as
      conventional methods. Instead, accurate prognostic stratification requires
      careful assessment of the likely metastatic potential of the primary cancer.

PMID- 14648709
TI  - High levels of circulating testosterone are not associated with increased
      prostate cancer risk: a pooled prospective study.
AB  - Androgens stimulate prostate cancer in vitro and in vivo. However, evidence from
      epidemiologic studies of an association between circulating levels of androgens
      and prostate cancer risk has been inconsistent. We investigated the association
      of serum levels of testosterone, the principal androgen in circulation, and sex
      hormone-binding globulin (SHBG) with risk in a case-control study nested in
      cohorts in Finland, Norway and Sweden of 708 men who were diagnosed with prostate
      cancer after blood collection and among 2,242 men who were not. In conditional
      logistic regression analyses, modest but significant decreases in risk were seen
      for increasing levels of total testosterone down to odds ratio for top vs. bottom
      quintile of 0.80 (95% CI = 0.59-1.06; p(trend) = 0.05); for SHBG, the
      corresponding odds ratio was 0.76 (95% CI = 0.57-1.01; p(trend) = 0.07). For free
      testosterone, calculated from total testosterone and SHBG, a bell-shaped risk
      pattern was seen with a decrease in odds ratio for top vs. bottom quintile of
      0.82 (95% CI = 0.60-1.14; p(trend) = 0.44). No support was found for the
      hypothesis that high levels of circulating androgens within a physiologic range
      stimulate development and growth of prostate cancer.

PMID- 14648710
TI  - Circulating levels of sex steroid hormones and risk of endometrial cancer in
      postmenopausal women.
AB  - Experimental and epidemiological data support a role for sex steroid hormones in
      the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood
      concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and
      SHBG with endometrial cancer risk were investigated. A case-control study was
      nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Cases
      were 124 postmenopausal women with invasive endometrial cancer. For each case, 2
      controls were selected, matching the case on cohort, age and date of recruitment.
      Only postmenopausal women who did not use exogenous hormones at the time of blood
      donation were included. Odds ratios (OR) and their 95% confidence intervals (CI)
      were estimated by conditional logistic regression. ORs (95% CI) for endometrial
      cancer for quartiles with the highest hormone levels, relative to the lowest were
      as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88),
      p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for
      androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42
      5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG
      after adjustment for body mass index, use of oral contraceptives and hormone
      replacement therapy. The results of our multicenter prospective study showed a
      strong direct association of circulating estrogens, androgens and an inverse
      association of SHBG levels with endometrial cancer in postmenopausal women. The
      effect of elevated androstenedione and testosterone levels on disease risk seems
      to be mediated mainly through their conversion to estrogens, although an
      independent effect of androgens on tumor growth cannot be ruled out, in
      particular in the years close to diagnosis.

PMID- 14648711
TI  - Comparison of risk factors for colon and rectal cancer.
AB  - Predictors of colorectal cancer have been extensively studied with some evidence
      suggesting that risk factors vary by subsite. Using data from 2 prospective
      cohort studies, we examined established risk factors to determine whether they
      were differentially associated with colon and rectal cancer. Our study population
      included 87,733 women from the Nurses' Health Study (NHS) and 46,632 men from the
      Health Professionals Follow Up Study (HPFS). Exposure information was collected
      via biennial questionnaires (dietary variables were collected every 4 years).
      During the follow-up period (NHS: 1980 to May 31, 2000; HPFS: 1986 to January 31,
      2000), we identified 1,139 cases of colon cancer and 339 cases of rectal cancer.
      We used pooled logistic regression to estimate multivariate relative risks for
      the 2 outcomes separately and then used polytomous logistic regression to compare
      these estimates. In the combined cohort, age, gender, family history of colon or
      rectal cancer, height, body mass index, physical activity, folate, intake of
      beef, pork or lamb as a main dish, intake of processed meat and alcohol were
      significantly associated with colon cancer risk. However, only age and sex were
      associated with rectal cancer. In a stepwise polytomous logistic regression
      procedure, family history and physical activity were associated with
      statistically significant different relative risks of colon and rectal cancer.
      Our findings support previous suggestions that family history and physical
      activity are not strong contributors to the etiology of rectal cancer. Future
      investigations of colon or rectal cancer should take into consideration risk
      factor differences by subsite.

PMID- 14648712
TI  - Lymphoproliferative disorders in autoimmune diseases in Japan: analysis of
      clinicopathological features and Epstein-Barr virus infection.
AB  - Lymphoproliferative disorders (LPD) occasionally develop in individuals with
      immune deficiencies such as immunosuppressive conditions and autoimmune diseases
      (AID). In our study, the clinicopathologic features and virus status were
      analyzed in 53 cases with LPD developing in rheumatoid arthritis (RA) and other
      AID. AID in only 4 of 53 patients had been treated with some sort of
      immunosuppressive therapy, including methotrexate. Median age at the diagnosis of
      LPD in AID was 60 years old with marked female predominance (M/F = 0.4). The
      median interval between the onset of AID and LPD development was 45 months, and
      longer in RA patients than in other AID (p < 0.01). The primary site of lymphoma
      was nodal in 21 cases and extra-nodal in 24, with clinical Stage I in 17, II in
      5, III in 13, and IV in 13. Immunohistochemistry showed that 39 cases were B cell
      type, 10 were T cell type and 4 were Hodgkin lymphoma (HL). Then majority of B
      cell cases were diffuse large B cell lymphomas, and 2 were diffuse polymorphic
      type. EBER-1 in situ hybridization for Epstein-Barr virus (EBV) showed positive
      signals in tumor cells in 16 of 53 (30.2%) cases. The EBV-positive rate in T cell
      LPD (70%) was much higher than that in B cell LPD (12.8%) (p < 0.01). All 4 cases
      of HL were EBV-positive. Immunohistochemistry showed a latency II pattern of EBV
      infection (LMP-1(+) and EBNA-2(-)). Five-year overall survival rate was 33%.
      Multivariate analysis showed that only type of AID was an independent factor for
      survival of patients, i.e., LPD in RA showed the most favorable prognosis. In
      conclusion, LPD in AID generally shared common features with sporadic LPD except
      for a much higher EBV-positive rate in T cell LPD.

PMID- 14648713
TI  - Incidence trends of adult primary intracerebral tumors in four Nordic countries.
AB  - Brain tumors are some of the most lethal adult cancers and there is a concern
      that the incidence is increasing. It has been suggested that the reported
      increased incidence can be explained by improvements in diagnostic procedures,
      although this has not been totally resolved. The aim of our study was to describe
      the incidence trends of adult primary intracerebral tumors in four Nordic
      countries during a period with introduction of new diagnostic procedures and
      increasing prevalence of mobile phone users. Information about benign and
      malignant primary intracerebral tumor cases 20-79 years of age was obtained from
      the national cancer registries in Denmark, Finland, Norway and Sweden for the
      years 1969-98 and estimates of person-years at risk were calculated from the
      information obtained from national population registries. Annual age standardized
      incidence rates per 100,000 person-years were calculated and time trends analyses
      were carried out using Poisson regression. The overall incidence of all
      intracerebral tumors ranged from 8.4-11.8 for men and 5.8-9.3 for women,
      corresponding to an average annual increase of 0.6% for men (95% confidence
      interval [CI] = 0.4, 0.7) and 0.9% for women (95% CI = 0.7, 1.0). The increase in
      the incidence was confined to the late 1970s and early 1980s and coinciding with
      introduction of improved diagnostic methods. This increase was largely confined
      to the oldest age group. After 1983 and during the period with increasing
      prevalence of mobile phone users, the incidence has remained relatively stable
      for both men and women.

PMID- 14648714
TI  - Identification of candidate antigens for serologic detection of Helicobacter
      pylori-infected patients with gastric carcinoma.
AB  - Helicobacter pylori colonizes the stomach of almost half the world population and
      is a causative agent of gastric carcinomas and duodenal ulcers. Only a small
      fraction of infected people will develop these severe illnesses and a predictive
      test to identify people at high risk would greatly benefit disease management.
      Our study aimed to identify conserved bacterial antigens that may be useful for
      the development of such a diagnostic test. High-resolution immunoproteomics by 2
      dimensional electrophoresis of H. pylori 26695 proteins was carried out with sera
      from infected patients with either duodenal ulcer (n=30) or gastric carcinoma
      (n=30), 2 clinically divergent conditions. According to their antigen recognition
      patterns clear groups of patients were identified. Although this classification
      did not correspond to the clinical status, it may be correlated to other
      bacterial or host factors that influence the outcome of infection. In general
      antigen recognition patterns were found to be highly variable, however by
      utilizing powerful image analysis and statistical tests the recognition of 14
      antigenic protein species was found to differ significantly (p<0.01) between both
      diseases. Particular protein species of GroEL, HyuA, GroES and AtpA appear to be
      useful surrogate markers for gastric carcinoma detection and consequently should
      be considered for further prospective studies to assess their predictive value.
      For one protein species of AtpA, evidence was found that different post
      translational modifications may confer different immunogenicities.

PMID- 14648715
TI  - Synergistic interaction between the EGFR tyrosine kinase inhibitor gefitinib
      ("Iressa") and the DNA topoisomerase I inhibitor CPT-11 (irinotecan) in human
      colorectal cancer cells.
AB  - Epidermal growth factor receptor [EGFR (HER1, erbB1)] is a receptor with
      associated tyrosine kinase activity, and is expressed in colorectal cancers and
      many other solid tumors. We examined the effect of the selective EGFR tyrosine
      kinase inhibitor (EGFR-TKI) gefitinib ("Iressa") in combination with the DNA
      topoisomerase I inhibitor CPT-11 (irinotecan) on human colorectal cancer cells.
      EGFR mRNA and protein expression were detected by RT-PCR and immunoblotting in
      all 7 colorectal cancer cell lines studied. Gefitinib inhibited the cell growth
      of the cancer cell lines in vitro with an IC(50) range of 1.2-160 microM by
      3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.
      Lovo cells exhibited the highest level of protein and autophosphorylation of EGFR
      and were the most sensitive to gefitinib. The combination of gefitinib and CPT-11
      induced supra-additive inhibitory effects in COLO320DM, WiDR and Lovo cells,
      assessed by an in vitro MTT assay. Administration of gefitinib and CPT-11 had a
      supra-additive inhibitory effect on WiDR cells and tumor shrinkage was observed
      in Lovo cell xenografts established in nude mice, whereas no additive effect of
      combination therapy was observed in COLO320DM cells. To elucidate the mechanisms
      of synergistic effects, the effect of CPT-11-exposure on phosphorylation of EGFR
      was examined by immunoprecipitation. CPT-11 increased phosphorylation of EGFR in
      Lovo and WiDR cells in time- and dose-dependent manners. This EGFR activation was
      completely inhibited by 5 microM gefitinib and gefitinib-induced apoptosis was
      enhanced by combination with CPT-11, measured by PARP activation although no PARP
      activation was induced by 5 microM CPT-11 alone. These results suggested that
      these modification of EGFR by CPT-11, in Lovo cells, is a possible mechanism for
      the synergistic effect of CPT-11 and gefitinib. These findings imply that the
      EGFR-TKI gefitinib and CPT-11 will be effective against colorectal tumor cells
      that express high levels of EGFR, and support clinical evaluation of gefitinib in
      combination with CPT-11, in the treatment of colorectal cancers.

PMID- 14648716
TI  - Nadir B cell counts are significantly correlated with the risk of Kaposi's
      sarcoma.
AB  - Infection with HIV-1 is known to impair B cell function. To further elucidate the
      role of B cells during infection and tumorigenesis, we studied their numbers in
      cases of AIDS-related Kaposi's sarcoma (KS) during the HAART era. Patients with
      AIDS-related KS were identified from a database of 4,480 HIV-1 positive
      individuals and the incidence of KS and rate ratio was stratified according to
      nadir number of B cells, measured as the CD19 count. In an unadjusted model, we
      observed that lower B cell counts were associated with a statistically
      significant increased risk of KS development (p < 0.001). We also observed a
      trend toward increased counts during KS resolution. When adjusted for nadir CD4
      count in a multi-variable model, higher B cell counts were protective against KS
      development (p = 0.015). These data highlight a potential role for B cells and
      therefore the humoral immune system in KS aetiopathogenesis.

PMID- 14648717
TI  - CHEK2 1100delC is not a risk factor for male breast cancer population.
AB  - Genetic risk factors for male breast cancer (MBC) are poorly understood. High
      penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of
      the disease. A 1100delC mutation in CHEK2 (previously known as CHK2), a cell
      cycle checkpoint kinase, has been implicated in predisposition of Li-Fraumeni
      syndrome (LFS) and breast cancer in families suggestive of LFS. This 1100delC
      mutation has also been shown to confer a 2-fold increase of breast cancer risk in
      women and a 10-fold increase of risk in men. It was estimated to account for 1%
      of breast cancers in women and as much as 9% of breast cancers in men at the
      population level based on analysis of breast cancer families without BRCA1 or
      BRCA2 mutations. We wanted to evaluate the significance of CHEK2 1100delC in
      predisposition to MBC by assessing its frequency in a population-based material
      of 114 Finnish MBC patients. Two patients (1.8%) carried the 1100delC mutation.
      The mutation frequency among MBC cases was similar to that seen in population
      controls (26/1885, 1.4%). Our results indicate that CHEK2 1100delC variant does
      not substantially increase the risk of male breast cancer at the population
      level. We cannot exclude the fact that a small fraction of hereditary, family
      positive male breast cancers could be attributable to CHEK2 mutations.

PMID- 14648718
TI  - Role of CHEK2*1100delC in unselected series of non-BRCA1/2 male breast cancers.

PMID- 14648719
TI  - CHEK2*1100delC and male breast cancer risk in Israel.

PMID- 14648721
TI  - Prosthetic implants for hernia repair.

PMID- 14648722
TI  - Immunonutrition.

PMID- 14648723
TI  - Arterial problems in athletes.
AB  - BACKGROUND: Athletes may present with arterial problems that are unusual in the
      typical patient with peripheral vascular disease. They are often handicapped only
      at the extremes of physical exertion and may have normal arterial pulses beyond
      any arterial occlusion. METHODS: A Medline search was undertaken for articles on
      arterial disease in athletes. Further papers were identified by cross-referencing
      from the reference lists. RESULTS: A variety of syndromes has been described that
      result from unusual trauma to arteries, causing occlusion or rupture. Frequently
      the blood flow and pressures distal to the arterial disease are normal at rest,
      and diagnosis is often confused with venous, musculoskeletal or nerve disease. A
      variety of operative interventions has been described. CONCLUSION: Athletes may
      experience arterial problems that may jeopardize their careers. If recognized
      promptly, operative intervention may permit a return to the highest level of
      sporting achievement.

PMID- 14648724
TI  - Ischaemia-reperfusion is an event triggered by immune complexes and complement.
AB  - BACKGROUND: Reperfusion injury is a common clinical problem that lacks effective
      therapy. Two decades of research implicating oxygen free radicals and neutrophils
      has not led to a single successful clinical trial. METHODS: The aim was to review
      new clinical and preclinical data pertaining to the alleviation of reperfusion
      injury. A review of the literature was undertaken by searching the MEDLINE
      database for the period 1966-2003 without language restrictions. RESULTS AND
      CONCLUSION: Evidence now points to complement and immune complexes as critical
      players in mediating reperfusion injury. Ischaemia is postulated to induce a
      phenotypical cellular change through the surface expression of a neoantigen.
      Preformed circulating natural IgM antibodies are then trapped and complement is
      activated. Final events leading to reperfusion injury include formation of the
      membrane attack complex and mast cell degranulation.

PMID- 14648725
TI  - Meta-analysis of randomized clinical trials comparing open and laparoscopic
      inguinal hernia repair.
AB  - BACKGROUND: The aim was to conduct a meta-analysis of the randomized evidence to
      determine the relative merits of laparoscopic (LIHR) and open (OIHR) inguinal
      hernia repair. METHODS: A search of the Medline, Embase, Science Citation Index,
      Current Contents and PubMed databases identified all randomized clinical trials
      that compared OIHR and LIHR and were published in the English language between
      January 1990 and the end of October 2000. The meta-analysis was prepared in
      accordance with the Quality of Reporting of Meta-analyses (QUOROM) statement. The
      six outcome variables analysed were operating time, time to discharge from
      hospital, return to normal activity and return to work, postoperative
      complications and recurrence rate. Random effects meta-analyses were performed
      using odds ratios and weighted mean differences. RESULTS: Twenty-nine trials were
      considered suitable for meta-analysis. Some 3017 hernias were repaired
      laparoscopically and 2972 hernias were repaired using an open method in 5588
      patients. For four of the six outcomes the summary point estimates favoured LIHR
      over OIHR; there was a significant reduction of 38 per cent in the relative odds
      of postoperative complications (odds ratio 0.62 (95 per cent confidence interval
      (c.i.) 0.46 to 0.84); P = 0.002), 4.73 (95 per cent c.i. 3.51 to 5.96) days in
      time to return to normal activity (P < 0.001), 6.96 (95 per cent c.i. 5.34 to
      8.58) days in time to return to work (P < 0.001) and 3.43 (95 per cent c.i. 0.35
      to 6.50) h in time to discharge from hospital (P = 0.029). There was a
      significant increase of 15.20 (95 per cent c.i. 7.78 to 22.63) min in the mean
      operating time for LIHR (P < 0.001). The relative odds of short-term recurrence
      were increased by 50 per cent for LIHR compared with OIHR, although this result
      was not statistically significant (odds ratio 1.51 (95 per cent c.i. 0.81 to
      2.79); P = 0.194). CONCLUSION: LIHR was associated with earlier discharge from
      hospital, quicker return to normal activity and work, and significantly fewer
      postoperative complications than OIHR. However, the operating time was
      significantly longer and there was a trend towards an increase in the relative
      odds of recurrence after laparoscopic repair.

PMID- 14648726
TI  - Randomized clinical trial of Ligasure versus conventional surgery for extended
      gastric cancer resection.
AB  - BACKGROUND: The Ligasure Vessel Sealing System is a haemostatic device designed
      primarily for use in abdominal surgery. Randomized trials have demonstrated that
      it is safe and quick for haemorrhoidectomy, but there is no evidence that it
      confers any advantage in complicated gastrointestinal surgery. The aim of the
      present study was to examine the value of the Ligasure system in extended lymph
      node dissection (D2) during gastrectomy for cancer in a randomized clinical
      trial. METHODS: D2 gastric resection performed with the Ligasure system was
      compared with resection using conventional haemostatic methods in a prospective
      randomized trial. Central randomization (40 patients in each group) was performed
      after a staging laparotomy. The main outcome measures were operating time,
      intraoperative blood loss, postoperative course and complications. RESULTS:
      Ligasure was associated with less intraoperative blood loss (mean(s.d.) 142(73)
      versus 239(124) ml; P = 0.001) and a shorter operating time (mean(s.d.) 169(25)
      versus 222(28) min; P = 0.001) than conventional operation. Postoperative
      drainage fluid volumes were greater in the Ligasure group (mean(s.d.) 1577(940)
      versus 886(542) ml; P = 0.020). There were no differences in postoperative
      complications or hospital stay. CONCLUSION: The Ligasure Vessel Sealing System is
      safe for use in extended lymph node dissection for gastric cancer, and is
      associated with a shorter operating time and decreased blood loss compared with
      conventional haemostatic techniques.

PMID- 14648727
TI  - Randomized clinical trial of multimodal optimization and standard perioperative
      surgical care.
AB  - BACKGROUND: Multimodal optimization of surgical care has been associated with
      reduced hospital stay and improved physical function. The aim of this randomized
      trial was to compare multimodal optimization with standard care in patients
      undergoing colonic resection. METHODS: Twenty-five patients requiring elective
      right or left hemicolectomy were randomized to receive a ten-point optimization
      programme (14 patients) or conventional care (11). The groups were similar in
      terms of age (64 versus 68 years), male : female sex ratio (6 : 8 versus 5 : 6)
      and Physiological and Operative Severity Score for the enUmeration of Mortality
      and morbidity (POSSUM) score (both 26). Outcome measures were recorded before
      operation and on postoperative days 1, 7 and 30. They included hand grip
      strength, lung spirometry, and pain and fatigue scores. Further outcome measures
      included time to achieve a predetermined mobilization target, time to resumption
      of normal diet, and length of stay. RESULTS: Optimization was associated with
      maintained grip strength, earlier mobilization (46 versus 69 h; P = 0.043), and
      significantly lower pain and fatigue scores. Patients in the optimization group
      tolerated a regular hospital diet significantly earlier than controls (48 versus
      76 h; P < 0.001). Optimization significantly reduced the median length of
      hospital stay (3 versus 7 days; P = 0.002). CONCLUSION: Optimization of surgical
      care significantly improved patients' physical and psychological function in the
      early postoperative period and facilitated early hospital discharge.

PMID- 14648728
TI  - Cosmesis and satisfaction after breast-conserving surgery correlates with the
      percentage of breast volume excised.
AB  - BACKGROUND: The cosmetic outcome after breast-conserving surgery correlates with
      psychosocial adjustment. Previous studies have shown that, among other factors,
      cosmesis is dependent on breast size and weight of the wide local excision
      specimen. This study assessed cosmetic outcome relative to a combination of these
      factors-the estimated percentage of breast volume excised (EPBVE). METHODS: The
      study group consisted of 151 women who had undergone breast-conserving surgery.
      All had previously completed a patient satisfaction questionnaire and an
      independent panel had assessed cosmetic outcome. Their mammograms were reviewed
      and breast volume was estimated. A validation series showed cone volume on the
      oblique mammogram to predict true breast weight most accurately (r = 0.93).
      RESULTS: Both subjective cosmetic assessment and patient satisfaction correlated
      strongly with EPBVE. Overall, when the EPBVE was below 10 per cent, 83.5 per cent
      of patients were very satisfied with their appearance and only 3.1 per cent were
      not satisfied, compared with 37.0 and 16.7 per cent respectively if the EPBVE was
      more than 10 per cent. However, tumour location in the breast was also an
      important factor; cosmetic outcome was worse for medial tumours. CONCLUSION: The
      percentage of breast volume excised was an important determinant of cosmesis and
      patient satisfaction after breast-conserving surgery. Calculating the EPBVE
      before surgery may help select women in whom breast reshaping or volume
      replacement should be considered.

PMID- 14648729
TI  - Persistent increase in the incidence of abdominal aortic aneurysm in Scotland,
      1981-2000.
AB  - BACKGROUND: In the 1970s and 1980s, mortality and morbidity rates for abdominal
      aortic aneurysm (AAA) increased throughout the developed world. As AAAs are
      associated with similar risk factors to other cardiovascular diseases that have
      recently decreased in incidence, the incidence of AAA should show a similar
      declining trend. METHODS: Routinely collected data were obtained on all primary
      diagnoses of aortic aneurysm resulting in death or hospital discharge in Scotland
      between 1981 and 2000. Trends in the data were analysed according to sex and age,
      aneurysm site and type of hospital admission. RESULTS: Between 1981 and 2000,
      42.3 per cent of the 10 822 deaths from aortic aneurysm in Scotland were
      attributed to the abdominal aorta. Age-adjusted mortality rates for AAA increased
      2.6-fold from 2.62 deaths per 100 000 in 1981 to 6.82 per 100 000 in 2000.
      Hospital admissions for AAA also rose threefold, with increases in both elective
      admissions (from 3.05 to 7.80 per 100 000) and emergency admissions (from 7.44 to
      11.23 per 100 000). CONCLUSION: The incidence of AAA has increased over the past
      20 years in Scotland. This is unlikely to be due simply to changes in detection
      and diagnosis, data inaccuracies, coding or ageing of the population. The
      incidence of both elective and emergency admission for AAA increased, suggesting
      that a genuine and persistent rise in the incidence of AAA has probably occurred.

PMID- 14648730
TI  - Endovascular management of traumatic cervicothoracic arteriovenous fistula.
AB  - BACKGROUND: This study evaluated a single-centre experience with endovascular
      repair of traumatic arteriovenous fistula in the cervicothoracic region. METHODS:
      Endovascular repair of 27 traumatic cervicothoracic arteriovenous fistulas was
      attempted between August 1998 and December 2001. Patients with active bleeding or
      end-organ ischaemia were excluded. Follow-up was accomplished with clinical,
      duplex Doppler and arteriographic evaluation after 1 month and then every 3
      months. RESULTS: Twelve patients with a major vessel injury were treated by stent
      graft placement. Vessels involved were the subclavian (eight), common carotid
      (three) and internal carotid (one) arteries. Subclavian artery side branches were
      embolized in three of the eight patients. Four patients developed early type 4
      endoleaks but all resolved. Treatment with stent-grafts was ultimately successful
      in all 12 patients. Three patients were lost to follow-up. During mean follow-up
      of 21 (range 3-36) months, one of the remaining patients developed a graft
      stenosis. Fifteen patients with minor vessel injuries were treated with arterial
      embolization. Vessels embolized were subclavian artery branches (four), external
      carotid artery and branches (seven) and vertebral arteries (four). Successful
      embolization was accomplished in ten of 15 patients. CONCLUSION: Endovascular
      therapy is a promising alternative to surgery for selected patients with
      cervicothoracic arteriovenous fistula.

PMID- 14648731
TI  - Prognostic significance of metastatic lymph node size in patients with gastric
      cancer.
AB  - BACKGROUND: Patients with gastric cancer that has metastasized to the lymph nodes
      are a heterogeneous population with a variable prognosis. Stratification of these
      patients into prognostic groups is necessary for optimal adjuvant therapy.
      METHODS: The study comprised 715 patients who had undergone curative resection of
      a gastric neoplasm. Lymph nodes were sectioned, stained with haematoxylin and
      eosin, and the diameter of the largest metastatic lymph node (MLN) was measured.
      Patients with metastatic nodes were divided into groups n1 and n2 according to
      the size of the MLN. The cut-off level was set at 7 mm by a two-sample log rank
      test; patients in group n1 had a MLN size of 7 mm or less and those in group n2
      had a MLN of 8 mm or more. RESULTS: Patients were stratified into significant
      prognostic groups by both the Union International Contra la Cancrum (UICC) node
      (N) stage and MLN size (n group). The UICC N-stage subcategories were further
      divided into prognostic groups according to MLN size (n group). On multivariate
      analysis the MLN size remained independently significant in terms of overall and
      disease-free survival rates, and the UICC N stage was not significant,
      independently of the n group. Node-positive patients with fewer than 15 lymph
      nodes removed at operation could also be stratified into prognostic groups by the
      n group. Stratification according to the TNM stage and by MLN size was superior
      to existing UICC TNM staging. CONCLUSION: This new method may help clinicians to
      design a more appropriate treatment strategy for patients with gastric cancer.

PMID- 14648732
TI  - Risk factors predicting the development of complications after foreign body
      ingestion.
AB  - BACKGROUND: The aim of this study was to determine the predictive risk factors
      for complications resulting from foreign body ingestion. METHODS: A consecutive
      series of 1338 patients with suspected foreign body ingestion presenting from
      1996 to 2000 were studied retrospectively. The potential risk factors for
      complications after foreign body ingestion were analysed by multivariate logistic
      regression and included concurrent medical illness, age, duration and types of
      symptoms, types of foreign body ingested, positive cervical radiographic findings
      and the level of foreign body impaction. RESULTS: Fish bone (62.7 per cent) was
      the commonest type of foreign body ingested. Most of the objects were impacted at
      or above the cricopharyngeus, the commonest site being the valleculae (31.4 per
      cent). Multivariate analysis showed that presentation delayed for more than 2
      days (P < 0.001), positive cervical radiographic findings (P < 0.001) and foreign
      body impacted at the cricopharyngeus (P = 0.009) or upper oesophagus (P = 0.005)
      were significant independent risk factors associated with the development of
      complications after foreign body ingestion. CONCLUSION: In patients with a
      foreign body seen on plain cervical radiography, presentation delayed for more
      than 2 days after ingestion, and foreign body impacted at the level of the
      cricopharyngeus or oesophagus there is a high degree of correlation with the
      occurrence of complications. Awareness should be raised when these risk factors
      are present.

PMID- 14648734
TI  - Increasing age and APACHE II scores are the main determinants of outcome from
      pancreatic necrosectomy.
AB  - BACKGROUND: The aim of this study was to identify factors associated with death
      after surgery in patients with extensive pancreatic necrosis. METHODS: Sixty-four
      patients who underwent pancreatic necrosectomy between 1996 and 2002 were
      studied. RESULTS: The median age was 60.5 (95 per cent confidence interval (c.i.)
      57 to 64) years and 40 patients (62.5 per cent) were tertiary referrals. The
      initial median Acute Physiology And Chronic Health Evaluation (APACHE) II score
      was 9 (95 per cent c.i. 7.9 to 10.1) and there were 21 deaths (32.8 per cent).
      Twenty-eight patients (43.8 per cent) underwent minimally invasive
      retroperitoneal pancreatic necrosectomy (MIRP) and the remainder had open
      pancreatic necrosectomy (OPN); 44 (72.1 per cent) of 61 patients had infected
      pancreatic necrosis at the time of the first procedure. Seven patients who
      underwent MIRP died compared with 14 after OPN (P = 0.240). Patients who died
      were older than those who survived, with higher APACHE II scores at presentation,
      and before and after surgery (P = 0.001). Survivors had significantly longer
      times to surgery than those who died (P = 0.038). All 21 patients who died
      required intensive care compared with 26 of 43 survivors (P < 0.001). Thirty of
      36 patients who had the OPN procedure required intensive care compared with only
      17 of 28 patients who had MIRP (P = 0.042). Logistic regression analysis showed
      that only postoperative APACHE II score was an independent predictor of increased
      mortality (P = 0.031). CONCLUSION: Advanced age and increasing APACHE II score,
      and a need for postoperative intensive care, were the most important predictors
      of outcome after pancreatic necrosectomy.

PMID- 14648733
TI  - Surgical treatment of hydatid cysts of the liver.
AB  - BACKGROUND: Echinococcosis is a zoonotic disease that occurs throughout the
      world. The purpose of this study was to assess the clinical features and results
      of surgical treatment of hepatic hydatid cysts. METHODS: One hundred and two
      patients operated on between 1991 and 2002 were reviewed retrospectively. The
      patients' demographic data, location, number and size of cysts, type of surgical
      procedure performed, morbidity, recurrences and duration of hospital stay were
      recorded. RESULTS: There were 74 male and 28 female patients with ages ranging
      from 15 to over 60 years. The most frequent symptom was abdominal pain. From the
      total of 136 hepatic cysts, 54 (39.7 per cent) were managed by cystostomy and
      drainage, 40 (29.4 per cent) by cystostomy and capitonnage, 16 (11.8 per cent) by
      cystostomy and omentoplasty, 24 (17.6 per cent) by cystectomy and two (1.5 per
      cent) by left lateral hepatic resection. Postoperative complications were more
      frequent following cystostomy with omentoplasty (six of 16 patients) compared
      with cystectomy (none of 18) (P = 0.005). Choledochotomy increased the length of
      hospital stay in patients having cystostomy and drainage (P = 0.021) and in those
      having cystostomy with omentoplasty (P = 0.028). Two recurrences were observed.
      CONCLUSION: Surgery combined with medical treatment by albendazole is effective
      in the eradication of hepatic hydatid disease and in the prevention of local
      recurrence.

PMID- 14648735
TI  - Predictors of improvement in health-related quality of life in patients
      undergoing cholecystectomy.
AB  - BACKGROUND: Few studies have assessed health-related quality of life (HRQoL)
      among patients undergoing cholecystectomy. This study aimed to determine clinical
      variables that predict changes in HRQoL following cholecystectomy. METHODS: This
      was a prospective study of consecutive patients undergoing elective
      cholecystectomy for gallstones in six hospitals. Patients were asked to complete
      two questionnaires-the Short Form 36 (SF-36) and the Gastrointestinal Quality of
      Life Index (GIQLI)-before and 3 months after cholecystectomy. Multivariate linear
      regression models were used to examine factors potentially contributing to
      changes in HRQoL. RESULTS: Patients with symptomatic cholelithiasis and low
      surgical risk experienced the highest HRQoL gains in several SF-36 and GIQLI
      domains, with significant improvements in physical function detected by both
      instruments, compared with asymptomatic individuals at high surgical risk.
      Patients with asymptomatic cholelithiasis or high surgical risk experienced least
      improvement. CONCLUSION: These data indicate that cholecystectomy is appropriate
      for patients with symptomatic cholelithiasis and low surgical risk. In terms of
      HRQoL, the risk to benefit ratio seems poor for patients with asymptomatic
      gallstones.

PMID- 14648736
TI  - Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer
      liver metastasis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have been reported to play an
      important role in tumour cell invasion and metastasis. The bioactivity of MMPs in
      liver metastasis from colorectal cancer was investigated and correlated with
      clinicopathological variables. METHOD: Thirty-two patients underwent resection of
      colorectal cancer liver metastases. Latent and active forms of MMP were measured
      in tissue extracts, by means of quantitative gelatin zymography and a
      fluorometric activity assay. RESULTS: Broad-spectrum MMP activity, and levels of
      both active and latent forms of MMP-2 and MMP-9, were higher in tissues
      containing metastatic tumour than in normal liver tissue. Median metastatic to
      normal tissue ratios were 15.0 and 17.6 for active and proMMP-2 respectively, and
      those for active and proMMP-9 were 6.2 and 2.9. The ratios of active to latent
      enzyme were higher in metastatic tissue than in normal tissue. Lowered MMP-2
      activity was associated with large metastatic lesions and increased proMMP-9
      levels with preoperative chemotherapy. Both MMP-2 and MMP-9 activity were linked
      unfavourably to early recurrent disease. CONCLUSION: These data suggest a role
      for MMPs in colorectal cancer liver metastasis, but indicate different roles for
      individual MMPs.

PMID- 14648737
TI  - Comparison of histological features and inflammatory cell reaction in alcoholic,
      idiopathic and tropical chronic pancreatitis.
AB  - BACKGROUND: There is increasing evidence that immune mechanisms may be crucial in
      the development of alcoholic chronic pancreatitis. However, it is not known
      whether differences in underlying aetiology influence the inflammatory reaction
      in patients with chronic pancreatitis. The histological features and the pattern
      of inflammatory cell infiltration were studied in three aetiological forms of
      chronic pancreatitis: alcoholic, idiopathic and tropical pancreatitis. METHODS:
      Forty-three patients, ten with alcoholic, 12 with idiopathic and 21 with tropical
      chronic pancreatitis, were evaluated for the pattern of pancreatic inflammatory
      cell infiltration and histological features. Ten organ donors served as controls.
      Haematoxylin and eosin-stained tissue sections were used for histological
      evaluation. For immunohistochemical characterization of the inflammatory
      reaction, four antibodies-CD4, CD8, CD45 and CD68-were used. Quantitative
      evaluation of the various cell infiltrates was performed with computer-assisted
      image analysis. The inflammatory cell infiltration pattern was also evaluated.
      RESULTS: The degree of endophlebitis and the overall density of plasma cells were
      greater in tropical than in alcoholic chronic pancreatitis. The grade of
      intralobular fibrosis was significantly higher in tropical chronic pancreatitis
      compared with the idiopathic form. No significant quantitative differences in the
      specific cellular infiltrates (CD4, CD8, CD45, CD68) were observed in the three
      different groups. However, the perivascular inflammation number score was
      significantly higher in alcoholic compared with idiopathic pancreatitis (P =
      0.037), and the perivascular inflammation area score was significantly lower in
      idiopathic than in alcoholic (P = 0.024) or tropical (P = 0.020) pancreatitis.
      CONCLUSION: Different aetiological forms of chronic pancreatitis result in
      similar histological features and a comparable inflammatory cell reaction,
      indicating that the disease, independent of the underlying aetiology, reaches a
      common immunological stage beyond which it appears to progress as a single
      distinctive entity.

PMID- 14648738
TI  - Symptoms and anal sphincter morphology following primary repair of third-degree
      tears.
AB  - BACKGROUND: Approximately 0.6-9 per cent of vaginal deliveries are complicated by
      third-degree tears. The precise impact of such injuries on future pelvic floor
      function remains unknown. The aim of this study was to define the extent of
      structural and physiological damage to the anal sphincter and to investigate
      anorectal function in women who sustained third-degree tears during vaginal
      delivery. METHODS: Fifty-six women who sustained a third-degree tear were
      investigated prospectively. All patients had a primary repair of the anal
      sphincter complex, and were assessed by anorectal physiology and endoanal
      ultrasonography at a mean of 3.6 months. Symptoms were assessed by direct
      personal interview and also by a self-completed questionnaire. RESULTS: Forty
      four patients had a persistent anal sphincter defect on ultrasonography. The mean
      resting and squeeze anal canal pressures were significantly lower in patients
      with a combined defect than in those in whom the repair was intact (P = 0.036 and
      P = 0.005 respectively). At direct interview three patients volunteered current
      symptoms of faecal and/or urinary incontinence whereas 32 reported bothersome
      symptoms on the questionnaire (P < 0.001). CONCLUSION: The anatomical and
      physiological damage sustained during third-degree tears appears to be much
      greater than is generally appreciated. Primary repair does not provide lasting
      integrity. A self-administered questionnaire appears to be more accurate in
      defining the symptomatology.

PMID- 14648739
TI  - Lateral pelvic lymph node dissection for advanced lower rectal cancer.
AB  - BACKGROUND: The oncological outcome of patients who underwent curative surgery
      for lower rectal cancer was investigated to clarify whether lateral pelvic lymph
      node dissection (LPLD) conferred any benefit. METHODS: A total of 246 patients
      who underwent curative surgery for stage II and III lower rectal cancer (below
      the peritoneal reflection) between 1985 and 1998 was reviewed. Forty-two of these
      patients did not undergo LPLD. RESULTS: Patients who did not undergo LPLD were
      older, more likely to have anterior resection and pelvic nerve preservation, and
      had smaller tumours and lymph node metastasis at an earlier stage than those who
      underwent LPLD. There was no difference in survival among patients with stage II
      and III disease between the two groups. However, in patients with pathological N1
      lymph node metastasis, the 5-year disease-free survival rate was 73.3 per cent in
      patients who had LPLD compared with 35.3 per cent among those who did not (P =
      0.013). Multivariate analysis showed that LPLD was a significant prognostic
      factor. CONCLUSION: LPLD improved the prognosis of patients with stage III
      disease and a small number of lymph node metastases. A randomized clinical trial
      is needed to verify the benefit of LPLD.

PMID- 14648740
TI  - Decline in admission rates for acute appendicitis in England.
AB  - BACKGROUND: The incidence of acute appendicitis declined in western countries
      between the 1930s and the early 1990s. The aim of this study was to determine
      time trends in hospital admissions for acute appendicitis in England between 1989
      1990 and 1999-2000, and in population mortality rates for appendicitis from 1979
      to 1999. METHODS: : Hospital Episode Statistics for admissions were obtained from
      the Department of Health and mortality data from the Office for National
      Statistics. RESULTS: Between 1989-1990 and 1999-2000, age-standardized hospital
      admission rates for acute appendicitis decreased by 12.5 per cent in male
      patients and by 18.8 per cent in female patients. The proportions of admissions
      that resulted in operation remained stable. Admission rates for non-specific
      mesenteric lymphadenitis fell. Admission rates for abdominal pain increased
      between 1989-1990 and 1995-1996, at which time the International Classification
      of Diseases codes changed. Between 1995-1996 and 1999-2000, admission rates for
      abdominal pain declined. Analysis of age-specific admission rates for acute
      appendicitis and abdominal pain from 1989-1990 to 1995-1996 showed that the
      decline in acute appendicitis could not be accounted for by a change in
      diagnostic practice. Mortality rates for acute appendicitis remained stable over
      the study period. CONCLUSION: Admission rates for acute appendicitis declined
      over the study period. This decline cannot be explained by reclassification.

PMID- 14648741
TI  - Comparison of P-POSSUM risk-adjusted mortality rates after surgery between
      patients in the USA and the UK.
AB  - BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of
      Mortality and morbidity (POSSUM) criteria have been used to assess surgical risk
      in patients in the UK. The aim was to determine how applicable these criteria are
      to patients undergoing surgery in the USA. METHODS: Two cohorts of patients
      undergoing major non-cardiac surgery were followed prospectively in the USA (n =
      1056) and the UK (n = 1539). Each patient was assigned a risk score for
      preoperative physiological status and operative severity using the established
      POSSUM criteria. Death in hospital was the primary outcome measure. For each
      patient a predicted risk of death was calculated from Portsmouth POSSUM (P
      POSSUM) methodology using an established equation. The relationships between
      predicted and observed mortality rates in each cohort were investigated by means
      of multivariate logistic regression. RESULTS: Within each cohort, an increase in
      risk estimated by P-POSSUM predicted an increase in observed mortality rate (P <
      0.001). For any given risk level, however, mortality rates were significantly
      higher in the UK cohort than in the US cohort (odds ratio 4.50 (95 per cent
      confidence interval 2.81 to 7.19); Z = 6.25, P < 0.001). CONCLUSION: An increase
      in predicted risk, based on the P-POSSUM methodology, was associated with a
      higher mortality rate in patients from both countries. However, risk-adjusted
      mortality rates following major surgery were four times higher in the UK cohort.
      These marked differences warrant validation in a larger number of centres.

PMID- 14648742
TI  - Prevalence of multiple endocrine neoplasia type 1 in young patients with
      apparently sporadic primary hyperparathyroidism or pancreaticoduodenal endocrine
      tumours.
AB  - BACKGROUND: The appropriate treatment for a sporadic endocrine tumour may be
      different from those that present as part of the multiple endocrine neoplasia
      type 1 (MEN1) syndrome. As primary hyperparathyroidism (pHPT) and
      pancreaticoduodenal endocrine tumours (PETs) are the most common organ
      manifestations of MEN1, the prevalence of germline mutations in the MEN1 gene was
      determined in young patients with apparently sporadic pHPT or PETs. METHODS:
      Eighteen of 705 patients with pHPT and 11 of 93 patients with PETs operated on
      between 1987 and 2001 had no family history of MEN1, only one organ manifestation
      and were aged 40 years or less at the time of diagnosis. Fifteen patients with
      pHPT and eight with PETs agreed to MEN1 gene mutation analysis, which was
      performed by single-strand conformational variant analysis and direct DNA
      sequencing. RESULTS: Two of 15 patients (13.3 (95 per cent confidence interval
      (c.i.) 1.6 to 40.4) per cent) with apparently sporadic pHPT had a MEN1 germline
      mutation. Both mutations were found in patients with pHPT due to multiglandular
      disease, whereas the remaining 13 patients had a solitary adenoma. None of the
      eight patients with PETs carried a MEN1 germline mutation. CONCLUSION: Sporadic
      pHPT due to multiglandular disease in patients younger than 40 years may
      represent the first organ manifestation of MEN1 despite a negative family
      history.

PMID- 14648743
TI  - Experimental evaluation of phospholipids and icodextrin in re-formation of
      peritoneal adhesions.
AB  - BACKGROUND: The formation of further adhesions after adhesiolysis is a major
      problem. Not all agents that are supposed to reduce de novo adhesions can reduce
      further adhesion formation. The efficacy and safety of intraperitoneally applied
      phospholipids has been shown previously. This study evaluated the influence of
      phospholipids and icodextrin on adhesion re-formation. METHODS: In an
      experimental study on 60 Chinchilla rabbits adhesions were induced by
      standardized abrasion of defined areas of the ventral abdominal wall, the caecum
      and the ileum. Open adhesiolysis was performed 10 days later. The animals
      randomly received either 1.5 per cent phospholipids, 4 per cent icodextrin or
      Ringer's lactate intraperitoneally. Half of the animals in each group were killed
      after a further 10 days and the remainder at 20 days. Adhesion formation was
      assessed by computer-aided planimetry and histopathological examination. RESULTS:
      Phospholipids (10 days: P = 0.001; 20 days: P = 0.012) and icodextrin (10 days: P
      = 0.006; 20 days: P = 0.055) reduced adhesion re-formation after both intervals
      compared with Ringer's lactate controls. CONCLUSION: Phospholipids and icodextrin
      were effective in preventing re-formation of adhesions.

PMID- 14648744
TI  - Human model of duodenogastro-oesophageal reflux in the development of Barrett's
      metaplasia (Br J Surg 2003; 90: 1120-1128).

PMID- 14648745
TI  - Magnetic resonance imaging for primary fistula in ano (Br J Surg 2003; 90: 877
      881).

PMID- 14648748
TI  - Natural course of acquired undescended testis in boys (Br J Surg 2003; 90: 728
      731).

PMID- 14648749
TI  - Recurrence and survival after mesorectal excision for rectal cancer (Br J Surg
      2003; 90: 974-980).

PMID- 14648750
TI  - Cyclo-oxygenase 2 inhibition in colorectal cancer therapy (Br J Surg 2003; 90:
      1055-1067).

PMID- 14648751
TI  - Influence of postoperative morbidity on long-term survival following liver
      resection for colorectal metastases (Br J Surg 2003; 90: 1131-1136).

PMID- 14648752
TI  - Evaluation of POSSUM and P-POSSUM scoring systems in assessing outcome after
      laparoscopic colectomy (Br J Surg 2003; 90: 1280-1284).

PMID- 14648753
TI  - Comparison of resection and radiofrequency ablation for treatment of solitary
      colorectal liver metastases (Br J Surg 2003; 90: 1240-1243).

PMID- 14648755
TI  - Supramolecular assembly of collagen triblock peptides.
AB  - The relationship between primary sequence and collagen triple-helix formation is
      relatively well characterized, while higher levels of structural assembly from
      these sequences is poorly understood. To address this gap, a new collagen-like
      triblock peptide design was used to study the relationship between amino acid
      sequence and supramolecular assembly. Four collagen-like peptides with the
      sequence (Glu)(5)(Gly-Xaa-Hyp-Gly-Pro-Hyp)(6)(Glu)(5) and corresponding to Xaa =
      alanine, proline, serine, or valine, and an analogous peptide without the
      glutamic acid end blocks, were solubilized in water at high concentrations (20
      150 mg/mL) and analyzed in optical polarizing microscopy and transmission
      electron microscopy. Some of the peptides self-assembled into supramolecular
      structures, the nature of which was determined by the core collagen-like
      sequence. The globular end blocks appeared necessary for these short triple-helix
      forming peptides to spontaneously organize into supramolecular structures in
      solution and also provided enhanced thermal stability based on CD analysis. The
      results indicate a strong dependence of the peptide triblock assembly behavior on
      the identity of the guest residue Xaa; nematic order when Xaa was valine, no
      organization when Xaa was serine, and banded spherulites displaying a cholesteric
      like twist when Xaa was proline or alanine. According to these results, the
      identity of the amino acid in position Xaa of the triplet Gly-Xaa-Yaa
      dramatically determined the type of supramolecular assembly formed by short
      triple helices based on collagen-triblock like sequences. Moreover, the
      structural organization observed for these collagen-triblock peptides was
      analogous to some assemblies observed for native collagen in vivo and in vitro.
      The amino acid sequence in the native collagen proteins may therefore be a direct
      determinant of the different supramolecular architectures found in connective
      tissues.

PMID- 14648756
TI  - Recombinant human elastin polypeptides self-assemble into biomaterials with
      elastin-like properties.
AB  - Processes involving self-assembly of monomeric units into organized polymeric
      arrays are currently the subject of much attention, particularly in the areas of
      nanotechnology and biomaterials. One biological example of a protein polymer with
      potential for self-organization is elastin. Elastin is the extracellular matrix
      protein that imparts the properties of extensibility and elastic recoil to large
      arteries, lung parenchyma, and other tissues. Tropoelastin, the approximately 70
      kDa soluble monomeric form of elastin, is highly nonpolar in character,
      consisting essentially of 34 alternating hydrophobic and crosslinking domains.
      Crosslinking domains contain the lysine residues destined to form the covalent
      intermolecular crosslinks that stabilize the polymer. We and others have
      suggested that the hydrophobic domains are sites of interactions that contribute
      to juxtaposition of lysine residues in preparation for crosslink formation. Here,
      using recombinant polypeptides based on sequences in human elastin, we
      demonstrate that as few as three hydrophobic domains flanking two crosslinking
      domains are sufficient to support a self-assembly process that aligns lysines for
      zero-length crosslinking, resulting in formation of the crosslinks of native
      elastin. This process allows fabrication of a polymeric matrix with solubility
      and mechanical properties similar to those of native elastin.

PMID- 14648757
TI  - Brownian dynamics simulations of glycolytic enzyme subsets with F-actin.
AB  - Previous Brownian dynamics (BD) simulations identified specific basic residues on
      fructose-1,6-bisphophate aldolase (aldolase) (I. V. Ouporov et al., Biophysical
      Journal, 1999, Vol. 76, pp. 17-27) and glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) (I. V. Ouporov et al., Journal of Molecular Recognition, 2001, Vol. 14,
      pp. 29-41) involved in binding F-actin, and suggested that the quaternary
      structure of the enzymes may be important. Herein, BD simulations of F-actin
      binding by enzyme dimers or peptides matching particular sequences of the enzyme
      and the intact enzyme triose phosphate isomerase (TIM) are compared. BD confirms
      the experimental observation that TIM has little affinity for F-actin. For
      aldolase, the critical residues identified by BD are found in surface grooves,
      formed by subunits A/D and B/C, where they face like residues of the neighboring
      subunit enhancing their electrostatic potentials. BD simulations between F-actin
      and aldolase A/D dimers give results similar to the native tetramer. Aldolase A/B
      dimers form complexes involving residues that are buried in the native structure
      and are energetically weaker; these results support the importance of quaternary
      structure for aldolase. GAPDH, however, placed the critical residues on the
      corners of the tetramer so there is no enhancement of the electrostatic potential
      between the subunits. Simulations using GAPDH dimers composed of either S/H or
      G/H subunits show reduced binding energetics compared to the tetramer, but for
      both dimers, the sets of residues involved in binding are similar to those found
      for the native tetramer. BD simulations using either aldolase or GAPDH peptides
      that bind F-actin experimentally show complex formation. The GAPDH peptide bound
      to the same F-actin domain as did the intact tetramer; however, unlike the
      tetramer, the aldolase peptide lacked specificity for binding a single F-actin
      domain.

PMID- 14648758
TI  - Topological effects on the electrophoretic mobility of rigid rodlike DNA in
      polyacrylamide gels.
AB  - The electrophoretic migration of rigid rodlike DNA structures with well defined
      topologies has been investigated in polyacrylamide (PA) hydrogels prepared by
      copolymerization of acrylamide and N, N'-methylenebisacrylamide. Previous studies
      have reported structural and dynamic characteristics of linear and branched DNA
      during electrophoresis in PA gels using a variety of experimental parameters.
      However, a thorough investigation aimed at establishing specific relationships
      between topological features of rigid rodlike DNA structures and their
      electrophoretic behavior is still needed. In order to study these topological
      effects on mobility, an intensive examination of the electrophoretic mobility of
      small linear and starlike DNA was performed. A series of model DNA structures
      with well-defined branched topologies were synthesized with varying molecular
      parameters, such as number of arms surrounding the branch point and arm length.
      The electrophoretic mobility of these structures was then contrasted with a
      series of data obtained using linear DNA of comparable molecular size. When large
      DNA stars (M >/= 60 bp) were compared with linear DNA of identical molecular
      weight, the Ferguson plots were quite different. However, small DNA stars (24-32
      bp) and linear analogues had identical Ferguson plots. This indicates that a
      different motional mode or greater interaction with the gel exists for the larger
      DNA stars. When the total molecular weight of the DNA stars was held constant and
      the number of arms varied, the Ferguson plots for all the stars were identical.
      Additionally, a critical pore size was reached when the ratio of linear DNA
      mobility to star DNA mobility increased dramatically. Thus, while the
      incorporation of a single branch point can produce a large reduction in mobility,
      above a critical molecular size, the incorporation of additional branch points
      does not appear to provide further reduction in mobility. This finding is
      consistent with the transport properties of large synthetic star polymers, where
      a large reduction in their diffusion coefficient is observed when a single branch
      is added. When additional arms are incorporated, large synthetic stars do not
      display an appreciable further reduction in diffusion coefficient. The effect of
      arm length on mobility for rigid rod DNA stars was also studied. For four-arm DNA
      stars, the mobility was found to scale as an exponential function of the arm
      length. Finally, a recently proposed phenomenological model was used to
      successfully fit the mobility data for linear rigid rod DNA at various
      concentrations of PA.

PMID- 14648759
TI  - Effect of water potential on sol-gel transition and intermolecular interaction of
      gelatin near the transition temperature.
AB  - The sol-gel transition of gelatin, measured by thermal analysis and viscosity
      measurement, was analyzed in terms of the change in hydration state of polymer
      molecules. A new thermodynamic model was proposed in which the effect of water
      potential is explicitly taken into account for the evaluation of the free energy
      change in the sol-gel transition process. Because of the large number of water
      molecules involved and the small free energy change in the transition process,
      the contribution of water activity, a(W), was proved to be not negligible in the
      sol-gel transition process in solutions containing such low-molecular cosolutes
      as sugars, glycerol, urea, and formamide. The gel-stabilization effect of sugars
      and glycerol was linear with a(W), which seemed consistent with the contribution
      of water potential in the proposed model. The different stabilization effect
      among sugars and glycerol was explained by the difference in solvent ordering,
      which affects hydrophobic interaction among protein molecules. The gel
      destabilization effect of urea and formamide could be explained only by the
      direct binding of them to protein molecules through hydrogen bonding. On the
      contrary, the polymer-polymer interaction, measured by the viscosity analysis, in
      polyethyleneglycol and dextran solutions was not sensitive to the change in a(W),
      suggesting that no substantial change in hydration state with a(W) occurred in
      these polymer solutions.

PMID- 14648760
TI  - Hydrophobic tendencies of polar groups as a major force in molecular recognition.
AB  - Proteins and nucleic acids are able to adopt their native conformation and
      perform their biological role only in the presence of water with which they
      actively interact in a mutually modifying way. Traditionally, hydrophobic effect
      has been considered to be the major factor stabilizing biopolymeric structures.
      However, solvent reorganization around polar groups is an event thermodynamically
      more unfavorable than solvent reorganization around nonpolar groups.
      Consequently, burial of polar groups with formation of complementary solute
      solute hydrogen bonds out of contact with water is an energetically favorable
      process that also provides a major force driving macromolecular association and
      folding. In contrast to nonpolar groups, polar groups may form their
      complementary intra- or intersolute hydrogen bonds out of contact with water only
      provided that an appropriate solute structure has been formed with properly
      positioned hydrogen bond donors and acceptors. Formation of such structures is
      disfavored entropically and may not be possible due to steric reasons. However,
      the interior of a folded protein, alpha-helices and beta-sheets, double helical
      nucleic acid structures, and protein-ligand interfaces all provide rigid matrices
      where polar groups may form their complementary hydrogen bonds. For these
      structures, the inward drive of polar groups represents a considerable
      stabilizing factor.

PMID- 14648761
TI  - Synthesis, conformation, and immunosuppressive activity of CLX and its analogues.
AB  - The CLX peptide isolated from flax seed has a sequence cyclo-(PPFFILLX), where X
      is a nonproteinaceous amino acid residue, (2S,4R) 4-amine-N-methylproline. Picur,
      B.; Lisowski, M.; Siemion, I.Z. Letters Pept Sci 1998, 5, 183-187. The structure
      of X strongly suggests that this natural amino acid plays a role of the dipeptide
      moiety with a nonplanar cis peptidomimetic bond. The X residue contains two
      asymmetrical carbons and thus can appear in four configurations: (2S,4R),
      (2S,4S), (2R,4S), and (2R,4R). All four diastereoisomers of X were synthesized
      and characterized as trifluoroacetates of 4-phtalimido-N-methylproline
      benzylamides. Their full physicochemical characteristics are presented in this
      article. The synthesis of linear and cyclic analogues of CLX containing all four
      possible diastereoisomers of X was performed. Additionally, analogues with gamma
      aminobutyric acid (GABA) and glycyl-N-methyl-glycine dipeptide [G(Me)G]
      substituted for X were synthesized. The obtained peptides were purified using
      HPLC, examined by ESI/MS, and then studied by CD spectroscopy. They were also
      tested for immunosuppressive activity (PFC in vitro). All of them revealed
      diverse immunosuppressive activity, however, lower than that of cyclolinopeptide
      A (CLA) Wieczorek, Z.; Bengtsson, B.; Trojnar, J.; Siemion, I.Z. Peptide Res
      1991, 4, 275-283. and cyclosporine A (CsA). Ellis, G.P.; West, G.B. Progress Med
      Chem 1988, 25, 1-33. The structure of CLX with (2S,4R) 4-amino-N-methylproline
      was determined by 2-D NMR methods. All amide bonds are in the trans
      configuration. The cis peptidomimetic group delta-CH(2)-N(CH(3))- is exposed to
      the outside of the CLX molecule. The peptide contains two loops similar to beta
      turns of type IV. Chou, P.Y.; Fasman, G.D. J Mol Biol 1977, 115, 136-715 and has
      the extended shape flanked by F3 and L7 residues with significant side chain
      flexibility.

PMID- 14648762
TI  - Structural alterations of enkephalins in the presence of GM1 ganglioside
      micelles.
AB  - The enkephalins are endogenous neurotransmitters and bind with high affinity at
      the delta-receptor. Gangliosides, the major glycans of nerve cells, known to
      interact both with receptors and ligands on the cell surface, have been
      implicated to modulate the actions of opioid receptors by allosteric regulation
      (Wu, G.; Lu, Z. H.; Wei, T. J.; Howells, R. D.; Christoffers, K.; Leeden R. W.
      Ann NY Acad Sci 1998, 845, 126-138). We have studied the interactions between
      enkephalins and monosialylated ganglioside GM1 using NMR spectroscopy and
      fluorescence. The structural models of enkephalins in the presence of GM1
      micelles were generated using two-dimensional (1)H-ROESY experiments along with
      restrained molecular dynamics simulations. We report a conformational alteration
      of enkephalins in the presence of GM1 micelles.

PMID- 14648763
TI  - Characterization of two molluscan crystal-modulating biomineralization proteins
      and identification of putative mineral binding domains.
AB  - Ethylenediamine-tetraacetic acid extracted water-soluble matrix proteins in
      molluscan shells secreted from the mantle epithelia are believed to control
      crystal nucleation, morphology, orientation, and phase of the deposited mineral.
      Previously, atomic force microscopy demonstrated that abalone nacre proteins bind
      to growing step edges and to specific crystallographic faces of calcite,
      suggesting that inhibition of calcite growth may be one of the molecular
      processes required for growth of the less thermodynamically stable aragonite
      phase. Previous experiments were done with protein mixtures. To elucidate the
      role of single proteins, we have characterized two proteins isolated from the
      aragonitic component of nacre of the red abalone, Haliotis rufescens. These
      proteins, purified by hydrophobic interaction chromatography, are designated AP7
      and AP24 (aragonitic protein of molecular weight 7 kDa and 24 kDa, respectively).
      Degenerate oligonucleotide primers corresponding to N-terminal and internal
      peptide sequences were used to amplify cDNA clones by a polymerase chain reaction
      from a mantle cDNA library; the deduced primary amino acid sequences are
      presented. Preliminary crystal growth experiments demonstrate that protein
      fractions enriched in AP7 and AP24 produced CaCO(3) crystals with morphology
      distinct from crystals grown in the presence of the total mixture of soluble
      aragonite-specific proteins. Peptides corresponding to the first 30 residues of
      the N-terminal sequences of both AP7 and AP24 were generated. The synthetic
      peptides frustrate the progression of step edges of a growing calcite surface,
      indicating that sequence features within the N-termini of AP7 and AP24 include
      domains that interact with CaCO(3). CD analyses demonstrate that the N-terminal
      peptide sequences do not possess significant percentages of alpha-helix or beta
      strand secondary structure in solution. Instead, in both the presence and absence
      of Ca(II), the peptides retain unfolded conformations that may facilitate protein
      mineral interaction.

PMID- 14648764
TI  - Conformational and biological characterization of human parathyroid hormone
      hPTH(1-34) analogues containing beta-amino acid residues in positions 17-19.
AB  - The N-terminal 1-34 fragment of parathyroid hormone (PTH) elicits the full
      spectrum of bone-related biological activities of the intact native sequences. It
      has been suggested that the structural elements essential for bioactivity are two
      helical segments located at the N-terminal and C-terminal sequences, connected by
      hinges or flexible points around positions 12 and 19. In order to assess the
      relevance of the local conformation around Gly(18) upon biological function, we
      synthesized and characterized the following human (h) PTH(1-34) analogues
      containing beta-amino acid residues: [analogues: see text]. Biological activity
      and binding affinity of analogue I are one order of magnitude lower than those of
      the parent compound. In analogue II, both binding affinity and biological
      activity are partially recovered. Analogues III and V have no binding affinity
      and very low biological activity. Both bioactivity and binding affinity are
      partially recovered in analogue IV. The conformational properties of the
      analogues in aqueous solution containing dodecylphosphocholine micelles were
      studied by CD, 2D-nuclear magnetic resonance and molecular dynamics calculations.
      The results confirmed the presence in all analogues of two helical segments
      located at the N-terminal and C-terminal sequences. The insertion of beta-amino
      acid residues around position 18 does not cause appreciable conformational
      differences in the five analogues. The differences in biological activity and
      binding affinity among the five analogues cannot be related to structural
      differences in the membrane mimetic environment reported in this study. Our
      results stress the importance of the side-chain functionalities in the sequence
      17-19 for biological function.

PMID- 14648765
TI  - Use of residual dipolar couplings as restraints in ab initio protein structure
      prediction.
AB  - NMR residual dipolar couplings (RDCs), in the form of the projection angles
      between the respective internuclear bond vectors, are used as structural
      restraints in the ab initio structure prediction of a test set of six proteins.
      The restraints are applied using a recently developed SICHO (SIde-CHain-Only)
      lattice protein model that employs a replica exchange Monte Carlo (MC) algorithm
      to search conformational space. Using a small number of RDC restraints, the
      quality of the predicted structures is improved as reflected by lower RMSD/dRMSD
      (root mean square deviation/distance root mean square deviation) values from the
      corresponding native structures and by the higher correlation of the most
      cooperative mode of motion of each predicted structure with that of the native
      structure. The latter, in particular, has possible implications for the structure
      based functional analysis of predicted structures.

PMID- 14648766
TI  - Volumetric characterization of homopolymeric amino acids.
AB  - We have determined the partial molar volumes, expansibilities, and adiabatic
      compressibilities for poly(L-alanine), poly(L-proline), and poly(L-threonine)
      within the temperature range of 18-55 degrees C. In addition, we have determined
      at 25 degrees C changes in volume, DeltaV, and adiabatic compressibility,
      DeltaK(S), associated with the coil-to-helix transitions of poly(L-lysine) and
      poly(L-glutamic acid) and the alpha-to-beta transition of poly(L-lysine). We have
      interpreted our volumetric data as suggesting that poly(L-alanine) and poly(L
      proline) are not fully unfolded and, probably, retain some solvent-inaccessible
      core. Further, we propose that poly(L-threonine) is fully unfolded with the
      majority of its atomic groups being solvent-exposed. Near zero changes in volume
      and compressibility accompanying the coil-to-helix transitions of poly(L-lysine)
      and poly(L-glutamic acid) suggest that, in the absence of fortuitous
      compensations, the coil-to-helix transitions of the polypeptides do not result in
      any significant enhancement of solute hydration. By contrast, the alpha-to-beta
      transition of poly(L-lysine) causes slight but statistically significant
      increases in volume and compressibility, an observation that may suggest that the
      beta-sheet conformation of poly(L-lysine) is slightly less hydrated than its
      alpha-helical conformation. In general, our results provide a quantitative
      volumetric description of the hydration properties of the homopolymeric
      polypeptides investigated. Such characterizations should prove useful in
      developing an understanding of the role that solvent plays in the
      stabilization/destabilization of folded protein structures and protein complexes.

PMID- 14648767
TI  - Application of statistical potentials to protein structure refinement from low
      resolution ab initio models.
AB  - Recently ab initio protein structure prediction methods have advanced
      sufficiently so that they often assemble the correct low resolution structure of
      the protein. To enhance the speed of conformational search, many ab initio
      prediction programs adopt a reduced protein representation. However, for drug
      design purposes, better quality structures are probably needed. To achieve this
      refinement, it is natural to use a more detailed heavy atom representation. Here,
      as opposed to costly implicit or explicit solvent molecular dynamics simulations,
      knowledge-based heavy atom pair potentials were employed. By way of illustration,
      we tried to improve the quality of the predicted structures obtained from the ab
      initio prediction program TOUCHSTONE by three methods: local constraint
      refinement, reduced predicted tertiary contact refinement, and statistical pair
      potential guided molecular dynamics. Sixty-seven predicted structures from 30
      small proteins (less than 150 residues in length) representing different
      structural classes (alpha, beta, alpha;/beta) were examined. In 33 cases, the
      root mean square deviation (RMSD) from native structures improved by more than
      0.3 A; in 19 cases, the improvement was more than 0.5 A, and sometimes as large
      as 1 A. In only seven (four) cases did the refinement procedure increase the RMSD
      by more than 0.3 (0.5) A. For the remaining structures, the refinement procedures
      changed the structures by less than 0.3 A. While modest, the performance of the
      current refinement methods is better than the published refinement results
      obtained using standard molecular dynamics.

PMID- 14648768
TI  - Fluorescence properties of labeled proteins near silver colloid surfaces.
AB  - The fluorescence properties of a monolayer of labeled avidin molecules were
      studied near silver island films. We first adsorbed a monolayer of biotinylated
      BSA as a base that was used to capture labeled avidin molecules. For labeled
      avidin on silver island films, we observed an increase of the fluorescence
      intensity of between 18 and 80 with one-photon excitation and up to several
      hundredfold or larger with two-photon excitation. The probes were moderately more
      photostable in the presence of silver islands. There was also a dramatic decrease
      in the lifetimes with the amplitude-weighted values decreasing from 7- to 35
      fold. The data suggest that these spectral changes are due to both increased
      rates of excitation near the metallic particles and increases in the rates of
      radiative decay. Because these silver island surfaces are very heterogeneous, we
      are hopeful that larger increases in intensity and photostability can be obtained
      for probes situated at an optimal distance from the ideal island surfaces.

PMID- 14648770
TI  - Nondestructive analyses of unsaturated fatty acid species in dietary oils by
      attenuated total reflectance with Fourier transform IR spectroscopy.
AB  - The aim of this study was to develop a nondestructive method to quantitate
      relative amounts of n-3 and n-6 polyunsaturated fatty acid (PUFA) species in
      vegetable oils and oil seeds using Fourier transform IR spectroscopy (FTIR). The
      alkene Cbond;H stretching vibrations of unsaturated fatty acids in oils showed IR
      absorption bands with various peak positions and intensities at around 3010 cm(
      1), depending on the extent of unsaturation and PUFA species. With the aid of
      partial least-squares regression analysis, the FTIR measurement could practically
      predict the content of each PUFA species in the oil to be tested. A calculation
      method was also presented to directly find PUFA species in oils from the FTIR
      spectra. This technique was applied to dried soybean seeds to demonstrate a
      nonhomogenous distribution of saturated fatty acids and PUFAs, as well as
      glycans, in soybean cross sections.

PMID- 14648769
TI  - Effects of metallic silver island films on resonance energy transfer between N,N'
      (dipropyl)-tetramethyl- indocarbocyanine (Cy3)- and N,N'-(dipropyl)-tetramethyl-
      indodicarbocyanine (Cy5)-labeled DNA.
AB  - Resonance energy transfer (RET) is typically limited to distances below 60 A,
      which can be too short for some biomedical assays. We examined a new method for
      increasing the RET distances by placing donor- and acceptor-labeled DNA oligomers
      between two slides coated with metallic silver particles. A N,N'-(dipropyl)
      tetramethylindocarbocyanine donor and a N,N'-(dipropyl)
      tetramethylindodicarbocyanine acceptor were covalently bound to opposite 5' ends
      of complementary 23 base pair DNA oligomers. The transfer efficiency was 25% in
      the absence of silver particles or if only one slide was silvered, and it
      increased to an average value near 64% between two silvered slides. The average
      value of the Forster distance increased from 58 to 77 A. The energy transfer data
      were analyzed with a model assuming two populations of donor-acceptor pairs:
      unaffected and affected by silver island films. In an affected fraction of about
      28%, the apparent energy transfer efficiency is near 87% and the Forster distance
      increases to 119 A. These results suggest the use of metallic silver particles to
      increase the distances over which RET occurs in biomedical and biotechnology
      assays.

PMID- 14648771
TI  - Conformational analysis of melittin in solution phase: vibrational circular
      dichroism study.
AB  - The vibrational absorption and vibrational circular dichroism (VCD) spectra of
      melittin in D(2)O solutions at different pH values, different salt
      concentrations, or different 2,2,2-trifluoroethanol (TFE) concentrations are
      recorded in the amide I' (1850-1600 cm(-1)) region. Two models are used to
      simulate this peptide in different conditions, and a coupled oscillator program
      is used to obtain the calculated absorption and VCD spectra. This study indicates
      that melittin adopts a mixed structure in D(2)O solution at low pH, low salt
      concentration, or low TFE concentration. With an increase in pH, salt
      concentration, or TFE concentration, the structure changes to alpha-helix and
      further increases lead to aggregation. These results demonstrate the versatility
      of VCD in probing the conformations of peptides under different environmental
      perturbations.

PMID- 14648772
TI  - Resonance Raman scattering of cytochrome P450 BM3 and effect of imidazole
      inhibitors.
AB  - Resonance Raman scattering from cytochrome P450 BM3 is obtained with a Raman
      microprobe using 406-nm excitation with an accumulation time of a few seconds.
      The small sample size and rapid measurement time make the routine
      characterization of P450 systems by resonance Raman spectroscopy easier. Addition
      of imidazole and imidazole derivatives as inhibitors causes the appearance of
      additional peaks due to vinyl modes, increases the relative intensity of
      symmetric modes that would be A(1g) in D(4h) symmetry, and causes a large drop in
      the intensity of nu(11). This information indicates that the ligation of
      imidazoles to the heme iron causes the alignment of the vinyl modes with the
      plane of the heme ring and reduces the out of plane distortion of the ring. The
      effect of both inhibitors is similar but there is a subtle difference in the
      extent of the reduction in the intensity of nu(11), which suggests that steric
      effects within the pocket are having some effect.

PMID- 14648773
TI  - Spectroscopic study of permanganate oxidation reactions of oligonucleotides
      containing single base mismatches.
AB  - The electrophoretic gel-based chemical cleavage of the mismatch method gives an
      incomplete view of the DNA conformational changes induced by a single base
      mismatch. This spectroscopic study investigates the permanganate oxidation
      reactions with matched and mismatched DNA under constant and variable temperature
      conditions. The results, which include the oxidation levels, reaction patterns
      with isosbestic points, color changes, thermal spectra, spectroscopy derivative,
      and gel separation and melting temperatures, provide a fundamental background for
      identification of oligonucleotides containing single base mismatches by chemical
      means.

PMID- 14648774
TI  - Binding and reversible denaturation of double-stranded DNA by Ff gene 5 protein.
AB  - The gene 5 protein (g5p) from Ff filamentous virus is a model single-stranded DNA
      (ssDNA) binding protein that has an oligonucleotide/oligosaccharide binding (OB)
      fold structure and binding properties in common with other ssDNA-binding
      proteins. In the present work, we use circular dichroism (CD) spectroscopy to
      analyze the effects of amino acid substitutions on the binding of g5p to double
      stranded DNA (dsDNA) compared to its binding to ssDNA. CD titrations of
      poly[d(A). d(T)] with mutants of each of the five tyrosines of the g5p showed
      that the 229-nm CD band of Tyr34, a tyrosine at the interface of adjacent protein
      dimers, is reversed in sign upon binding to the dsDNA, poly[d(A). d(T)]. This
      effect is like that previously found for g5p binding to ssDNAs, suggesting there
      are similarities in the protein-protein interactions when g5p binds to dsDNA and
      ssDNA. However, there are differences, and the possible perturbation of a second
      tyrosine, Tyr41, in the complex with dsDNA. Three mutant proteins (Y26F, Y34F,
      and Y41H) reduced the melting temperature of poly[d(A). d(T)] by 67 degrees C,
      but the wild-type g5p only reduced it by 2 degrees C. This enhanced ability of
      the mutants to denature dsDNA suggests that their binding affinities to dsDNA are
      reduced more than are their binding affinities to ssDNA. Finally, we present
      evidence that when poly[d(A). d(T)] is melted in the presence of the wild-type,
      Y26F, or Y34F proteins, the poly[d(A)] and poly[d(T)] strands are separately
      sequestered such that renaturation of the duplex is facilitated in 2 mM Na(+).

PMID- 14648775
TI  - Tryptophanyl substitutions in apomyoglobin affect conformation and dynamic
      properties of AGH subdomain.
AB  - The solvent accessibilities to the tryptophanyl microenvironments of wild type
      sperm whale apomyoglobin (apoMb) and two mutants (W7F and W14F) containing a
      single tryptophan are measured by fluorescence quenching studies. The results are
      compared to those relative to horse apoMb. In the wild type sperm whale protein,
      no difference is noticed in the solvent accessibility of the two indole residues,
      as documented by the values of the Stern-Volmer constants. By contrast, the two
      tryptophan residues of horse apoMb are exposed to the solvent in a different way,
      thus indicating that some local conformational differences exist between the two
      homologous proteins in solution. The single W --> F substitution at either
      position 7 or 14 determines local conformational changes that increase the
      accessibility of the remaining indole residue but do not affect the overall
      architecture of the protein molecule.

PMID- 14648776
TI  - Effects of aluminum sorption on calcium-polygalacturonate network used as soil
      root interface model.
AB  - The objective of this study is to determine the influence of aluminum sorption on
      a calcium-polygalacturonate (Ca-PG) network used as a soil-root interface model.
      The Ca-PG network is exposed to aluminum solutions at different concentrations
      (25-800 microM) at pH 3.50. High concentrations lead to a release of calcium
      (80%) and aluminum becomes the predominant reticulating cation of the
      polygalacturonic chains. The FTIR spectra show how aluminum sorption induces
      shifts of the characteristic bands of carbohydrates in the spectral regions of
      1700-1400 and 1200-800 cm(-1), which are enhanced by decreasing intensities. This
      might be induced by a weakening of the metal-PG complex through conformational
      variations of the structure. Scanning electron micrographs also show a collapse
      of the fibrillar structure of Ca-PG that is due to aluminum sorption. This
      structural rearrangement suggests that the soil-root interface could modify its
      functionality, affecting the transport of metal ions (nutrients) across the
      interface and consequently through the cell membranes.

PMID- 14648779
TI  - Combined-modality therapy for gastric cancer.
AB  - Gastric cancer has a poor prognosis. It is often diagnosed at an advanced stage,
      and potentially curative treatments often can not be exercised. Even when a
      curative surgical resection is possible, only a minority of patients survive
      beyond 5 years, and locoregional failures are frequent among patients undergoing
      curative resections. Recently, the use of postoperative adjuvant
      chemoradiotherapy has yielded some notable benefits. Earlier studies have shown
      survival benefits in patients undergoing chemoradiotherapy for locally advanced
      unresectable gastric cancer. The recently reported Intergroup 0116 trial compared
      surgery alone with surgery plus postoperative chemotherapy plus
      chemoradiotherapy. Superior overall and disease-free survival rates among
      patients given combined-modality postoperative therapy were observed. These
      results established a new standard of care for patients following resection of
      gastric carcinoma. Preoperative combined-modality chemoradiotherapy may improve
      resectability, and is under investigation at the University of Texas M. D.
      Anderson Cancer Center. The development of novel radioenhancers and the selection
      of therapy on the basis of molecular determinants of response may result in much
      needed advances in this field.

PMID- 14648780
TI  - Combined modality therapy in esophageal cancer: the Memorial experience.
AB  - Over the past 20 years in the United States, esophageal cancer has shown the most
      rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an
      aggressive disease, and poor survival is achieved with surgery or chemoradiation
      therapy alone. Ongoing trials are investigating the use of preoperative
      chemoradiation followed by surgical resection. Chemoradiation employing a
      combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is
      the most commonly used therapy. The significant gastrointestinal toxicity of
      traditional cisplatin/5-FU-based regimens has prompted the evaluation of new
      agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center
      has conducted chemoradiation trials with weekly paclitaxel/cisplatin and
      irinotecan/cisplatin, and the results suggest that this regimen has the potential
      to improve the therapeutic index without compromising efficacy. Randomized trials
      are now being conducted to evaluate the tolerance and efficacy of
      paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with
      radiotherapy in locally advanced esophageal cancer. The incorporation of these
      non-5-FU-based therapies with novel biologic agents is planned.

PMID- 14648781
TI  - Gastrectomy, peritonectomy, and perioperative intraperitoneal chemotherapy: the
      evolution of treatment strategies for advanced gastric cancer.
AB  - Gastric cancer disseminates by hematogenous, lymphatic, and transcoelomic routes.
      For maximal containment of the malignant process, perioperative intraperitoneal
      chemotherapy is necessary in two groups of patients in whom the primary cancer
      can be resected. Those patients who have been resected for cure and have a high
      likelihood of microscopic residual disease require intraperitoneal chemotherapy.
      This includes all T3 and T4 patients, and patients with N2 nodes present. A
      series of randomized and nonrandomized clinical studies have established the
      benefits of perioperative intraperitoneal chemotherapy in this group of patients.
      Patients with stage IV disease who are able to undergo a palliative resection
      require these treatments if peritoneal seeding is observed. Systemic chemotherapy
      is largely ineffective for peritoneal seeding, while intraperitoneal chemotherapy
      is most likely to produce a response with small volume, surgically debulked
      carcinomatosis. In addition, intraperitoneal chemotherapy can eliminate the
      future development of debilitating ascites. Sufficient data are available from
      the gastric cancer literature to support the use of these combined treatments on
      a routine basis if the primary cancer is resectable and gastrointestinal function
      can be reestablished.

PMID- 14648782
TI  - Conformal chemoradiation for primary and metastatic liver malignancies.
AB  - Historically, radiation therapy has played a minor role in the management of
      patients with unresectable primary hepatobiliary malignancies and liver
      metastases from colorectal cancer. This can be attributed chiefly to the low
      tolerance of the whole liver to radiation. Three-dimensional radiation planning
      techniques have allowed much higher doses of radiation to be delivered to focal
      liver tumors, while sparing the majority of the normal liver. When combined with
      fluorodeoxyuridine (FUdR), high-dose focal liver radiation is associated with
      excellent response rates, local control, and survival in patients with large
      unresectable tumors. There appears to be a radiation dose response for
      intrahepatic malignancies. Advancements in tumor imaging, radiation techniques
      that can safely deliver higher doses of radiation, novel tumor radiation
      sensitizers, and normal-tissue radioprotectors should substantially improve the
      outcome of patients with unresectable intrahepatic malignancies treated with
      chemoradiation.

PMID- 14648783
TI  - Postoperative adjuvant therapy for pancreatic cancer.
AB  - The majority of patients diagnosed with pancreatic cancer present at an advanced
      stage, and only a small percentage are considered technically resectable at
      diagnosis. The overall prognosis for the majority is dismal, with a median
      survival in untreated cases of only 24 weeks. Even in resected patients the
      overall 5-year survival rate is generally only 5% to 10%; however, some reports
      indicate higher 5-year survival rates in patients treated with surgery who are
      pathologically staged with no lymph node involvement. Even when macroscopically
      complete resection is achieved, local recurrence (LR) rates are unacceptably high
      (30% to 70%), which is usually attributed to the difficulty of obtaining
      microscopically free surgical margins. Microscopic clearance is difficult to
      achieve because these tumors frequently extend into the peripancreatic tissues
      (e.g., retropancreatic fat), abut or invade the adjacent large vessels (the
      portal vein and superior mesenteric artery), and have a propensity to invade the
      lymphovascular and perineural space. Other common sites of failure after
      attempted curative resection include metastasis to the liver and the peritoneal
      cavity. Patients who present with pancreatic cancer, and for whom curative
      surgery is deemed possible, are thus potential candidates for adjuvant therapy
      because of the high local failure rate following resection alone. The
      radiotherapy dose that can be achieved in the postoperative setting for
      pancreatic cancer is limited because of the proximity of critical structures
      (e.g., the kidney, liver, small intestines, stomach, and spinal cord). Newer
      techniques such as conformal radiotherapy and intensity-modulated radiotherapy
      have the advantage of being able (theoretically) to precisely localize the dose
      to the target volume while reducing the dose to critical structures. These
      techniques may potentially enable the tumorcidal dose to be increased; however,
      they are only now becoming widespread. Systemic radiation-sensitizing
      chemotherapy is also a promising approach to take advantage of additive or
      synergistic effects with radiation locally, and for the sterilization of systemic
      disease. This concept of concomitant chemotherapy with radiotherapy, or
      chemoradiotherapy, has proved effective in a number of sites, including the anal
      canal, rectum, lung, and pancreas. The recent trials reviewed here varied
      considerably in terms of the total dose and technique used, and the choice of
      radiation sensitizing treatment.

PMID- 14648784
TI  - Preoperative chemoradiation for locally advanced rectal adenocarcinoma-the
      University of Florida experience.
AB  - To evaluate the efficacy of preoperative radiotherapy alone or combine with
      chemotherapy. Between 1975 to 1997, 318 patients with locally advanced rectal
      adenocarcinomas were treated with preoperative radiation therapy. Between 1991
      and 1997, approximately 60% of patients received fluorouracil (5-FU)-based
      adjuvant chemotherapy. Patients treated since 1991 had improved downstaging
      compared with those treated prior to 1991. Patients treated between 1991 and 1997
      were also more likely to undergo a sphincter preserving surgical procedure.
      Preoperative chemoradiation probably results in improved downstaging and survival
      compared with preoperative irradiation alone.

PMID- 14648785
TI  - Preoperative chemoradiation for locally advanced rectal cancer: rationale,
      technique, and results of treatment.
AB  - Over the past decade, 392 patients with stage II and III rectal cancer have been
      managed with preoperative chemoradiation and surgery at the M. D. Anderson Cancer
      Center (MDACC). Aggressive surgical techniques such as total mesorectal excision,
      proctectomy with coloanal anastamosis, and multivisceral excisions have been
      used. Initial pelvic chemoradiation is also used in patients who present with
      metastases. Preoperative chemoradiation followed by surgery has resulted in
      excellent sphincter preservation (SP) and pelvic control with minimal acute,
      perioperative, and late morbidity. SP has been achieved in greater numbers of
      patients over the past 3 years due to the increased use of coloanal anastamosis
      in very low tumors. There has been no increase in pelvic failure or perioperative
      morbidity with this practice. Patients with clinical T4 disease have
      significantly worse pelvic control. An assessment of the impact of CB on pelvic
      control and survival requires further follow-up. Poor differentiation and poor
      response to preoperative therapy predict a worse overall survival. Durable
      symptom control without colostomy has been achieved using initial chemoradiation
      in patients who present with metastases. Aggressive bowel management and skin
      care can minimize hospitalization and treatment interruption due to acute
      toxicity. Multidisciplinary therapy using preoperative chemoradiation and
      aggressive surgery has resulted in excellent SP and pelvic control. However, more
      effective systemic therapies are needed, especially for patients who do not
      respond well to preoperative chemoradiation.

PMID- 14648786
TI  - Immunocytochemical evaluation of estrogen receptor on archival Papanicolaou
      stained fine-needle aspirate smears.
AB  - The availability of limited fine-needle aspirate smears necessitates the
      selection of immunocytochemical (IC) methods that allow reuse of Pap-stained
      smears to assess the estrogen receptor (ER) status of breast carcinoma. The
      objective of the current study was to compare IC evaluation of ER status on FNA
      smears by three methods: 1) ER-ICA using H222 monoclonal antibody performed on
      slides fixed in formaldehyde-methanol-acetone; 2) destained Pap slides using 1D5
      antibody; and 3) Pap-stained slides without destaining using the same 1D5
      antibody. Two representative Pap smears of breast carcinoma were selected from 48
      cases of breast carcinoma in which ER was previously evaluated by ER-ICA. One of
      these Pap smears was used as such and the other was destained prior to
      immunostaining by a modified ABC method using 1D5 monoclonal antibody. The number
      of cells with positive nuclear staining was expressed as a percentage and the
      intensity of staining was semiquantitatively scored on a scale of 1+ to 3+. The
      degree of agreement between the three methods was evaluated statistically by
      weighted kappa statistics. Thirty cases (63%) showed varying degrees of positive
      staining while 18 cases (38%) were entirely negative by all three methods.
      Significant discrepancies in the number of cells with positive staining and in
      the intensity of staining between the three methods occurred in 40% and 23% of
      the cases and was mainly due to a reduction in the number of cells with positive
      staining and the intensity of staining using Pap slides in comparison to ER-ICA.
      Weighted kappa agreement of the percentage of cells with positive staining using
      Pap-stained slides and destained Pap-slides in comparison to ER-ICA was 0.75 and
      0.64, respectively, and that for the intensity of staining was 0.75 and 0.66,
      respectively. Therefore, IC evaluation of ER using Pap-stained smears as such or
      destained Pap smears compared favorably with ER-ICA. However, Pap-stained smears
      used as such for ER immunostaining showed a slightly better agreement with ER-ICA
      than destained Pap smears. Because significant differences in ER-IC staining can
      occur with any of the immunocytochemical methods, a negative result is less
      reliable as an indicator of true ER status than a positive result.

PMID- 14648787
TI  - Fine-needle aspiration of superficial and deeply seated lymph nodes on patients
      with and without a history of malignancy: review of 439 cases.
AB  - This study addresses the utility of fine-needle aspiration (FNA) in assessing
      lymphadenopathy in patients with and without a previous history of malignancy. We
      reviewed the FNAs of superficial and deeply seated lymph nodes performed at our
      institution over a period of 18 yr (1983-2001). Where applicable, we also
      reviewed and report here the results of subsequent surgical excisional biopsies.
      We analyzed data from 439 patients, who ranged in age from 1 to 90 yr. The neck
      and retroperitoneum were the most frequently sampled sites (47% and 25%,
      respectively). Among the 439 FNAs, adequate material was obtained in 421 cases
      (96%); the remaining 18 were unsatisfactory (4.1%). Malignant diagnoses were
      rendered in 330 cases (75% of 439), four were suspicious for lymphoma (0.9%), and
      87 were read as reactive lymph nodes or granulomas (20%). The most common
      malignant cytologic diagnoses from these lymph node FNAs were adenocarcinoma,
      squamous cell carcinoma, and lymphoma. We compared results between two major
      groups: patients with a history of malignancy and those without. FNA showed
      malignancy in 87% of patients with a history of cancer and 41% without such a
      history. Thirty-three or 10% of patients with a history of malignancy were given
      a benign diagnosis and follow-up surgical excisional biopsies were performed in
      nine of these cases. Four of the nine showed low-grade lymphoma. Of the 18 non
      diagnostic FNAs, nine came from patients with a history of malignancy and in six
      of these nine who had a follow-up surgical excisional biopsy the lymph nodes were
      positive for malignancy. Of the other nine, who had no history of malignancy,
      only two had follow-up biopsies and both of these were negative. Patients with a
      history of malignancy are more than twice as likely to show malignancy on lymph
      node FNA compared to those without such a history (87% vs. 41%). Knowing whether
      a patient has a history of malignancy provides the appropriate level of suspicion
      for ordering ancillary investigations or even recommending excisional biopsy for
      further evaluation.

PMID- 14648788
TI  - Comparative fine-needle aspiration and pathologic study of malignant fibrous
      histiocytoma: cytodiagnostic features of 95 tumors in 71 patients.
AB  - To determine diagnostic cytomorphologic features of malignant fibrous
      histiocytoma (MFH) on fine-needle aspiration (FNA) materials, we reviewed the
      cytologic material and corresponding histologic slides of 95 tumors in 71
      patients. Forty-four (46%) tumors were primary, 38 (40%) were recurrent, and 13
      (14%) were metastatic. Histological variants of MFH were as follows: 52 (54.7%,
      43 patients) were of the storiform/pleomorphic, seven (7.4%, five patients) were
      giant cells, four (4.2%, four patients) were inflammatory, and 31 (33.7%, 19
      patients) were myxoid type. Review of original cytology reports showed that only
      23 (24.2%) tumors were diagnosed as MFH and 68 (71.6%) as other types of
      malignancies. Four (4.2%) cases were reported as unsatisfactory/suspicious. Our
      findings showed that spindle-shaped, round, giant cells, osteoclastic-like giant,
      and inflammatory cells were the most consistent features that allow
      identification of the storiform/pleomorphic, giant cell, and inflammatory
      variants of MFH. The myxoid tumors had marked myxoid background matrix with
      spindle-shaped cells and, less frequently, round and giant cells. Pleomorphic
      leiomyosarcoma and dedifferentiated liposarcoma should be considered in the
      differential diagnosis of stroriphorm/pleomorphic, giant cells, and inflammatory
      variants of MFH. However, myxoid MFH may resemble their leiomyosarcoma and
      liposarcoma counterparts.

PMID- 14648790
TI  - Statistical analysis of cytologic features useful in separation of metastatic
      urothelial carcinoma from other metastatic epithelial malignancies.
AB  - The identification of a site of origin and direction of differentiation for
      metastatic neoplasms is clinically important, but is often difficult purely by
      cytologic analysis of aspirated material. Cytologic separation of metastatic
      urothelial carcinoma (UC) from other moderate or poorly differentiated epithelial
      malignancies is difficult, with few cytologic criteria identified in the
      literature as valuable for this distinction. Several investigators have suggested
      that "cercariform cells" (CCs) are highly correlated with the presence of
      metastatic UC. We statistically analyzed the utility of 37 cytomorphologic
      features for the recognition of urothelial differentiation in a series of 26
      metastatic UCs, 10 metastatic squamous cell carcinomas (SCCs), and 15 metastatic
      adenocarcinomas (ADCs). All specimens had been obtained from metastatic deposits
      in the lung, liver, lymph nodes, or soft tissues. Stepwise discriminate function
      analysis with all three diagnoses showed that the strongest discrimination could
      be made using the findings of waxy metaplastic cytoplasm, with significant
      increments in prediction added by analysis for (CCs) followed by spindle cells,
      multiple nucleoli, and columnar-shaped cells. The combination of these five
      variables accurately predicted 90% of all diagnoses, including 26 accurate
      diagnoses of UC, 9 accurate diagnoses of SCC, and 11 accurate diagnoses of ADC.
      CCs were present in highest numbers in UCs and present least frequently in cases
      of poorly differentiated ADC. While CCs were useful in the identification of UC,
      CCs occurred in a significant number of SCCs, limiting their diagnostic value as
      a single variable.

PMID- 14648789
TI  - Elastofibroma dorsi has distinct cytomorphologic features, making diagnostic
      surgical biopsy unnecessary: cytomorphologic study with clinical, radiologic, and
      electron microscopic correlations.
AB  - Elastofibroma dorsi (EFD) is a relatively rare soft tissue mass, probably of
      reactive nature. The lesion is typically located near the inferior margin of the
      scapula or between the inferior part of scapula and the chest wall in elderly
      women. Although location of the tumor together with the age/sex of the patients
      and radiologic findings is often suggestive of the diagnosis, tissue examination
      has been considered necessary to confirm the diagnosis. Although the histologic
      features of EFD are well known, there are only four single case reports of the
      cytologic findings in the English language literature. We describe the cytologic
      features of EFD in five patients with correlations to clinical, radiologic,
      histologic, and electron microscopic findings. The current study suggests that
      the fine-needle aspiration (FNA) features are highly diagnostic, permitting a
      firm diagnosis of EFD in a typical clinical setting and eliminating the need for
      preoperative histologic examination.

PMID- 14648791
TI  - Significance of psammoma bodies on a cervical sample from an asymptomatic woman.

PMID- 14648792
TI  - Sequence confirmation of the EWS-WT1 fusion gene transcript in the peritoneal
      effusion of a patient with desmoplastic small round cell tumor.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated neoplasm.
      The prognosis is poor, even if therapy is instituted promptly, and thus it is
      important to differentiate it from other histologically and cytologically similar
      looking malignancies of the young adult. We present a case of DSRCT in a 17-yr
      old male with disseminated peritoneal disease and peritoneal effusion. The
      cytology sample showed a malignant small round cell tumor, the classical
      cytological features of DSRCT, and immunohistochemistry performed in the prepared
      cell block exhibited an antibody expression profile in keeping with DSRCT.
      Further material from the effusion was prepared for RNA extraction, following
      which a reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing
      of the t(11;22)(p13;q11 or q12) were carried out. The result showed the presence
      of the reciprocal translocation and thus confirmed the diagnosis of DSRCT. This
      case shows how molecular techniques (including sequencing) can be applied to
      cytology in clarifying and confirming certain difficult diagnosis of
      undifferentiated neoplasms, DSRCT in this particular case.

PMID- 14648793
TI  - Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast
      lesions.
AB  - Fine-needle aspiration cytology (FNAC) is an established, highly accurate method
      for diagnosing breast lesions. However, in recent years there has been increased
      use of core biopsy (CB) in this setting. The aim of this study was to evaluate
      the accuracy of FNAC and compare the quality assessment parameters of FNAC and CB
      in palpable and nonpalpable breast lesions. Data regarding FNAC, CB, and excision
      biopsy (EB) diagnoses were retrieved from the archives of our department. A total
      of 4,367 FNAC samples from the years 1999-2001 was reviewed. Of these,
      corresponding histology results were available for 1,275 lesions, of which 1,248
      were primary breast epithelial lesions (788 EB, 199 CB, 261 EB+CB). All cases
      were analyzed for sensitivity and specificity of FNAC. Cases with both FNAC and
      CB were compared and quality assessment parameters were calculated using the
      methodology detailed in the National Health Service Breast Screening Program
      guidelines. High specificity and sensitivity, as calculated for satisfactory
      specimens, were achieved with the use of both FNAC and CB. False-positive and
      false-negative diagnoses were seen in 7/404 (1.7%) and 45/635 (7.1%) of biopsy
      proven specimens sampled by FNAC. The corresponding values for CB were 0% and
      5.7%, respectively. Inadequate sampling (15.1%) with use of FNAC was particularly
      seen in collagenous lesions and in submitted specimens sampled by physicians
      lacking experience with the FNAC procedure. FNAC is a valuable method, although
      moderately less sensitive than CB. CB is the preferred method for preoperative
      diagnosis when sampling FNAC provides scarce material and suspicion of a fibrotic
      and collagenous lesion such as lobular carcinoma and radial scar arises. FNAC is
      most accurate when experienced cytologists are available and when immediate
      assessment by professionals is performed for evaluation of material adequacy, so
      that additional aspirations can be done when needed.

PMID- 14648794
TI  - Intranuclear inclusions in a case of pigmented villonodular synovitis of the
      ankle.
AB  - Pigmented villonodular synovitis (PVNS) is a proliferative disorder of the
      synovial lining of the joints. Although the cytological findings of this disorder
      have been described in the literature, there is no mention of intranuclear
      cytoplasmic inclusions in this entity. A 65-yr-old woman presented with a painful
      swelling on the ankle. In addition to other characteristic findings of PVNS, we
      found the presence of intranuclear cytoplasmic inclusions in the fine-needle
      aspiration (FNA) smears. The characteristic cytological findings of abundant
      mononuclear cells occurring singly and in papillary clusters, multinucleated
      giant cells, and hemosiderin deposition should aid in the diagnosis of PVNS and
      in its differentiation from melanoma and other soft tissue sarcomas, even in the
      presence of uncommon features such as intranuclear inclusions.

PMID- 14648795
TI  - Melanotic neuroectodermal tumor of infancy in the soft tissues of the arm: fine
      needle aspiration biopsy and histologic correlation-a case report.
AB  - A case of melanotic neuroectodermal tumor of infancy (MNTI) presenting as a soft
      tissue mass in the right arm of a 6-mo female child is discussed. The mass was
      diagnosed by fine-needle aspiration biopsy (FNAB) and confirmed by histological
      examination. This communication emphasizes the characteristic cytology of MNTI
      and discusses its significance in the context of this tumor occurring in the soft
      tissues. The cytology smears were distinctive in showing a dual population of
      small, rounded, undifferentiated cells and larger melanin-containing epithelial
      like cells. It is the identification of the latter cells in the smears which
      differentiates this tumor from other round cell tumors of infancy and helps in
      the correct diagnosis by FNAB.

PMID- 14648796
TI  - Prostatic epithelial polyp diagnosed in a bladder wash.
AB  - Prostatic epithelial polyps, also known as adenomatous polyps or papillary
      adenomas with prostatic type epithelium, are uncommon lesions. These lesions
      typically involve the adult male urethra, trigone, or bladder dome. Diagnosis is
      usually made by biopsy. Presence of clusters of benign columnar cells in urine
      cytologic material can suggest the presence of such polyps and must be included
      in the differential diagnosis.

PMID- 14648797
TI  - Cytological diagnosis of nonulcerative penile neoplasms: report of two cases.
AB  - Nonulcerative penile mass lesions are rare. Pathological diagnosis of these
      lesions would traditionally be a biopsy. We report two such primary penile
      lesions which were diagnosed by fine-needle aspiration cytology (FNAC). Both
      lesions were present in the shaft and were diagnosed as squamous cell carcinoma
      (SCC). The first patient had a recurrence on the penile stump of partial
      amputation without any ulceration. The second had a primary urethral carcinoma on
      the terminal penile shaft infiltrating the corpora cavernosa dorsally. Open
      biopsies were avoided in both cases. FNAC was associated with very little and
      tolerable discomfort. There were no complications. The aspirate yield was
      sufficient for cytological diagnosis. FNAC of nonulcerated penile lesions is
      safe, well tolerated, and capable of providing a cytological diagnosis. Hence, it
      is a very useful outpatient procedure and could be the procedure of choice for
      diagnosis.

PMID- 14648798
TI  - Aggressive papillary male breast carcinoma on fine-needle cytology sample.
AB  - Papillary carcinoma (PC) is a histological variant of breast carcinoma that is
      more frequently observed in males than in females, showing the same cytological
      features in both sexes. PC is characterized by a low grade of malignancy and a
      generally favorable course. We describe a case of male breast PC (MPC) diagnosed
      by fine-needle cytology (FNC) in which some aggressive morphologically detectable
      features were associated with bland cytologic features of the tumor. FNC was
      performed on a 3 cm palpable mass of the left breast of a 55-yr-old male. FNC
      yielded abundant bloody material. Two smears were Diff-Quik and Papanicolaou
      stained, others were used for immunocytochemical assessment of estrogen,
      progesterone, c-erbB-2, and Ki-67; another was Feulgen stained for DNA ploidy.
      Smears were highly cellular, showing isolated cells and papillary structures.
      Cells showed tall and well-defined cytoplasm with a columnar aspect, light
      anisonucleosis, coarse chromatin, and small nucleoli. Immunoperoxidase staining
      demonstrated positivity for estrogen (50%), negativity for progesterone, intense
      positivity for c-erbB-2, with specific membrane staining and positivity for Ki-67
      in more than 20% of the cells. DNA-ploidy showed an aneuploid histogram with 5c
      exceeding rate (5cER) of 59% and 2c deviation index (2cDI) of 29%. Subsequent
      surgical pathology examination confirmed the cytological diagnosis of papillary
      carcinoma; moreover, it revealed neoplastic endolymphatic thrombi and
      infiltrative border of the tumor that reached the thoracic wall. Cytological
      features can suggest diagnosis of MPC on FNC samples. Immunocytochemical
      evaluation of c-erbB-2 and Ki-67 and DNA ploidy evaluation on cytological smears
      might reveal a biological aggressiveness of PC despite the bland microscopic
      features of the tumor and this should influence the therapeutic procedure.

PMID- 14648799
TI  - Ergonomics and cytotechnologists: reported musculoskeletal discomfort.
AB  - Analysis of this survey of 244 responding cytotechnologists shows that a high
      percentage still suffer from musculoskeletal disorders commonly associated with
      poor ergonomic design in the workplace, despite the variety of ergonomically
      designed microscopes that have been introduced into the market. Although Kalavar
      and Hunting surveyed a small group of cytotechnologists in the Washington, DC,
      area in 1996, no broad-based study has focused specifically on these
      professionals. The landmark study of microscope ergonomics, published by
      Soderberg in 1980, documented widespread musculoskeletal complaints in the
      electronics industry. This article identifies and discusses the types of
      musculoskeletal discomforts experienced by cytotechnologists. We propose that
      both practicing and student cytotechnologists receive training in ergonomic
      principles and appropriate interventions, such as improved work practices, proper
      ergonomic aids, well-designed workstations, and ergonomically designed equipment.
      More than 85% of respondents reported some musculoskeletal discomfort. Among the
      symptoms presented are headache, neck pain and stiffness, pain of the lower and
      upper back, and upper-extremity discomfort. Neurological symptoms, such as
      numbness, tingling, and/or pain in the hand and fingers, are often associated
      with repetitive motion. More than one-third reported numbness, tingling, and/or
      pain in the left-hand fingers, usually used for the fine-focus control knob.
      Almost one-half of respondents reported such symptoms for the right hand and
      fingers, normally used to manipulate the mechanical stage controls. Only 9% of
      the respondents were left-handed. Most (91%) were right handed. Although just
      over one-third (34.4%) of respondents worked for an employer with an ergonomics
      program, ergonomic assessments had been performed for only about one-half (17.6%)
      of these. In addition, approximately 10% of respondents indicated that ergonomics
      assessments had been performed on their workstations, even though the employer
      did not have an ergonomics program. Because of the high prevalence of reported
      symptoms, we recommend that all cytologists be trained in basic ergonomic
      principles and the proper use of ergonomic aids. These interventions should
      reduce the prevalence of musculoskeletal discomfort in medical microscopists.

PMID- 14648800
TI  - Cytologic diagnosis of follicular dendritic cell tumor: a diagnostic dilemma.

PMID- 14648802
TI  - Enteroviruses and type 1 diabetes.
AB  - The development of type 1 diabetes mellitus (T1DM) has been linked to exposure to
      environmental triggers, with Enteroviruses (EV) historically considered the prime
      suspects. Early serological studies suggested a link between EV infections and
      the development of T1DM and, though controversial, have been bolstered by more
      recent studies using more sensitive techniques such as direct detection of the EV
      genome by RT-PCR in peripheral blood. In this review, we consider the weight of
      evidence that EV can be considered a candidate trigger of T1DM, using three major
      criteria: (1) is EV infection associated with clinical T1DM, (2) can EV trigger
      the development of autoimmunity and (3) what would explain the putative
      association?

PMID- 14648803
TI  - Vascular endothelial growth factor and diabetic retinopathy: pathophysiological
      mechanisms and treatment perspectives.
AB  - Retinal neovascularization and macular edema are central features of diabetic
      retinopathy, the major cause of blindness in the developed world. Current
      treatments are limited in their efficacy and are associated with significant
      adverse effects. Characterization of the molecular and cellular processes
      involved in vascular growth and permeability has led to the recognition that the
      angiogenic growth factor and vascular permeability factor vascular endothelial
      growth factor (VEGF) plays a pivotal role in the retinal microvascular
      complications of diabetes. Therefore, VEGF represents an exciting target for
      therapeutic intervention in diabetic retinopathy. This review highlights the
      current understanding of the mechanisms that regulate VEGF gene expression and
      mediate its biological effects and how these processes may become altered during
      diabetes. The cellular and molecular alterations that characterize experimental
      models of diabetes are considered in relation to the influence of high glucose
      mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's
      actions under hyperglycemic induction. Finally, potential therapeutic strategies
      for preventing VEGF overexpression or blocking its pathological effects in the
      diabetic retina are considered.

PMID- 14648804
TI  - The role of phospholipase D in Glut-4 translocation.
AB  - Insulin-stimulated Glut-4 translocation is regulated through a complex pathway.
      Increasing attention is being paid to the role undertaken in this process by
      Phospholipase D, a signal transduction-activated enzyme that generates the lipid
      second-messenger phosphatidic acid. Phospholipase D facilitates Glut-4
      translocation at potentially multiple steps in its outward movement. Current
      investigation is centered on Phospholipase D promotion of Glut-4-containing
      membrane vesicle trafficking and vesicle fusion into the plasma membrane, in part
      through activation of atypical protein kinase C isoforms.

PMID- 14648805
TI  - Reduced cumulative incidence of diabetes but not insulitis following
      administration of chimeric human IL-15-murine IgG2b in NOD mice.
AB  - BACKGROUND: It has been recently demonstrated that apoptosis is involved in beta
      cell destruction in the NOD mouse model of diabetes. The aim of the present study
      was to investigate whether IL-15, a cytokine involved in the modulation of the
      apoptotic process, is capable of modifying the natural history of diabetes and/or
      insulitis in pre-diabetic NOD mice. The rationale for the use of IL-15-IgG2b
      recombinant cytokine is related to its long half-life (28 +/- 4 h). METHODS: At
      10 weeks of age, 2 groups of 24 female mice were treated with single or multiple
      i.p. doses of IL-15-IgG2b respectively. As control, 2 groups of 24 age- and
      litter-matched female mice were injected intra-peritoneally with single or
      multiple doses of IgG2b immunoglobulin. RESULTS: Diabetes incidence at 33 weeks
      of age was lower in the group of mice treated with multiple doses than in the
      control group (p = 0.03). The cumulative incidence of diabetes at 33 weeks of age
      between single-dose treated mice and the control group was similar. No
      significant differences in the calculated index of insulitis were observed in all
      treated and control mice. CONCLUSIONS: We conclude that IL-15-IgG2b reduces the
      cumulative incidence of diabetes, without affecting the extent and severity of
      the insulitis process. Considering this and the well-defined anti-apoptotic
      effects of IL-15, we suggest that the reduction of diabetes incidence could be
      due to a down-regulation of beta-cell apoptosis.

PMID- 14648806
TI  - Nerve conduction velocity and evoked potential latencies in streptozotocin
      diabetic rats: effects of treatment with an angiotensin converting enzyme
      inhibitor.
AB  - BACKGROUND: Diabetes mellitus is associated with deficits in cerebral function.
      Vascular disorders may play a role in the pathogenesis and provide a potential
      target for treatment. The present study examined if prevention and intervention
      treatment with the angiotensin converting enzyme inhibitor enalapril could
      improve peripheral and central neurophysiological deficits in streptozotocin
      diabetic rats. METHODS: Sciatic nerve conduction velocities were measured prior
      to diabetes induction and again every three weeks. In the prevention study, the
      final nerve conduction measurements were performed at 15 weeks and in the
      intervention study at 24 weeks. Brain stem auditory and visual evoked potential
      latencies were measured every 3 weeks from 10 weeks after diabetes induction. In
      the prevention study, the final evoked potential measurements were performed at
      16 weeks and in the intervention study at 25 weeks. Treatment with the
      angiotensin converting enzyme inhibitor enalapril was started directly after
      diabetes induction (prevention treatment) and after 15 weeks of diabetes
      (intervention treatment). RESULTS: Nerve conduction velocity, brain stem auditory
      and visual evoked potential latencies were impaired in diabetic rats. Enalapril
      prevented deficits in nerve conduction velocity (p < 0.001), brain stem auditory
      evoked potential latencies (p < 0.01) and visual evoked potential latencies (p <
      0.005). Enalapril intervention treatment had no effect on nerve conduction
      velocity and on visual evoked potential latencies, but improved brain stem
      auditory evoked potential latencies (p < 0.05) after 10 weeks of treatment.
      CONCLUSION: Enalapril partially prevents the development of neurophysiological
      alterations in the peripheral and central nervous system and partially reverses
      deficits in brain stem auditory evoked potential latencies in STZ-diabetic rats.

PMID- 14648807
TI  - Effects of Atorvastatin on LDL sub-fractions and peroxidation in type 1 diabetic
      patients: a randomised double-blind placebo-controlled study.
AB  - BACKGROUND: Patients with diabetes have an increased risk of both developing and
      dying from cardiovascular disease, and, currently, more aggressive lipid-lowering
      targets are being recommended for these patients. Statins are widely and
      successfully used to correct dyslipidemia and prevent acute coronary episodes,
      but their effects on lipoprotein composition and peroxidation have not been fully
      investigated. We aimed to address this issue in type 1 diabetes mellitus.
      METHODS: T1DM patients with atherogenic index (total/HDL-cholesterol > 4) were
      randomised double-blindly to group A (n = 12) that received Atorvastatin 40
      mg/day and group P (n = 12) that received placebo. They were monitored for blood
      biochemistry, LDL sub-fractions and lipid peroxidation at inclusion, after 6 and
      after 12 weeks. RESULTS: In group A, the 40% decrease in serum total and LDL
      cholesterol and 20% decrease in triglycerides was accompanied by a decrease in
      serum alpha-tocopherol from 46.4 +/- 16.3 (mean +/- SD) at inclusion to 32.2 +/-
      11.8 and 32.6 +/- 14.0 micromol/L after 6 and 12 weeks respectively (p < 0.001
      compared to group P by repeated-measures ANOVA). Relative to LDL + VLDL
      cholesterol, alpha-tocopherol increased by 40% (p < 0.001). Copper-induced LDL +
      VLDL peroxidation increased from 4891 +/- 1325 at inclusion to 6821 +/- 2291 and
      7040 +/- 1712 nmol TBARS/mg LDL + VLDL cholesterol produced in 3 h (p = 0.004).
      LDL sub-fractions shifted towards the less dense regions (p = 0.03). CONCLUSIONS:
      These results suggest that Atorvastatin lowers the antioxidant capacity of LDL
      and VLDL in T1DM. The mechanisms underlying these changes merit further
      investigation and should be taken into account when planning long-term primary
      prevention of CHD in diabetes.

PMID- 14648808
TI  - Left-ventricular diastolic dysfunction may be prevented by chronic treatment with
      PPAR-alpha or -gamma agonists in a type 2 diabetic animal model.
AB  - OBJECTIVES: The aim of this study was to determine whether the peroxisome
      proliferator-activated receptor (PPAR) ligands could prevent left-ventricular
      diastolic dysfunction (LVDD) in rats with advanced diabetes. In addition, this
      study examined whether the activity of malonyl-CoA decarboxylase (MCD), which is
      an enzyme related to the degradation of malonyl-CoA that is known to regulate the
      fatty acid metabolism, is changed by the diabetic state itself or by treatment
      with the PPAR ligands. METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF)
      rats, a model of type 2 diabetes, aged 28 weeks, were divided into 3 groups: the
      untreated, pioglitazone-treated (10 mg/kg/d), and fenofibrate-treated (150
      mg/kg/d) groups. The rats were treated for 10 weeks. Male Long-Evans Tokushima
      Otsuka (LETO) rats were used as nondiabetic control. Doppler echocardiography and
      measurements of the MCD activity at the myocardium were performed. RESULTS: At
      the age of 38 weeks, the OLETF rats treated with either pioglitazone or
      fenofibrate showed an improvement in the plasma glucose levels after glucose
      loading as well as an improvement in the fasting plasma insulin, triglyceride,
      and FFA levels compared to the untreated OLETF rats. The untreated OLETF rats
      showed a prolonged deceleration time of the E-wave (DTE) (74.3 +/- 3.7 vs LETO,
      56.3 +/- 3.8 ms, P < 0.05) and a reduced ratio of the peak early diastolic
      velocity wave to the late diastolic wave (E/A ratio) (1.25 +/- 0.06 vs LETO 1.54
      +/- 0.08, P < 0.05). Pioglitazone treatment in the OLETF rats improved the DTE
      (51.6 +/- 1.7 ms, P < 0.05), and the fenofibrate treatment also improved the DTE
      (61.4 +/- 4.3 ms, P < 0.05) and E/A ratio (1.57 +/- 0.05, P < 0.05) compared to
      the untreated OLETF rats. The parameters related to the systolic function did not
      change among the groups at both pre- and post-treatments. The MCD activity of the
      myocardium was remarkably lower in the OLETF rats compared to the LETO rats (3.26
      +/- 0.38 vs 7.76 +/- 0.84 nmol/min/mg protein, P < 0.05). The pioglitazone and
      fenofibrate treatments resulted in an increase in the MCD activity compared to
      that in the untreated rats (7.20 +/- 0.74 and 8.33 +/- 0.83 nmol/min/mg protein,
      P < 0.05, respectively). CONCLUSIONS: The PPAR-alpha or -gamma agonists prevented
      LVDD in the advanced diabetic rat hearts, possibly through an improvement in the
      fatty acid metabolism in the myocardium or a correction of the hyperglycemia
      and/or hyperlipidemia.

PMID- 14648812
TI  - Infants and children with hearing loss--part 2: Overview.

PMID- 14648813
TI  - Diagnostic testing for hearing loss in infants and young children.
AB  - An early, reliable diagnosis and description of hearing loss is essential in
      determining appropriate treatment to minimize potential developmental delays
      attributed to the loss. Objective assessment of auditory function is possible
      shortly after birth. Both objective and subjective measures of auditory status
      are used in a test battery approach to determine the type, degree, and
      configuration of the hearing loss. This paper reviews the diagnostic test
      procedures used to define the hearing capability of infants and young children.
      For the youngest infants electrophysiologic tests, primarily auditory evoked
      potentials, are used to estimate hearing sensitivity. Later behavioral
      audiometric measures based on operant conditioning techniques become the primary
      component of the test battery. Diagnostic audiologic assessment is an ongoing
      process that requires special equipment and expertise when directed to infants
      and young children.

PMID- 14648814
TI  - Auditory neuropathy/dys-synchrony: diagnosis and management.
AB  - Auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs) are
      objective measures of auditory function, but are not hearing tests. Normal OAEs
      reflect normal cochlear outer hair cell function, and an ABR indicates a
      synchronous neural response. It is quite possible for a patient to have normal
      OAEs but absent or grossly abnormal ABR and a behavioral audiogram that is
      inconsistent with either test. These patients, who may constitute as much as 10%
      of the diagnosed deaf population, have auditory neuropathy/dys-synchrony (AN/AD).
      To diagnose AN/AD accurately, ABRs are obtained in response to condensation and
      rarefaction clicks to distinguish cochlear microphonics (CM) from neural
      responses. Appropriate management is confounded by variation among patients and
      changes in auditory function in some patients over time. Recommendations for
      management include visual language exposure through methods such as American Sign
      Language (ASL), Cued Speech, or baby signs, and closely following patients.

PMID- 14648815
TI  - Families and children with hearing loss: grief and coping.
AB  - Parental coping with the diagnosis of their child's hearing impairment has not
      received a great deal of research attention, despite the evident importance of
      it. Parental coping has been changing with the inception of newborn screening as
      we move from a parent-initiated model of diagnosis to an institution-initiated
      model. Coping now begins without any preparation, and without any time for
      parents to "enjoy" their child as "normal." The grief models, based on the death
      experience, usually employed to describe parental reactions to the diagnosis may
      also be inappropriate. Death grief is terminable whereas parental grief is
      chronic. There is not sufficient research on the long-term effects of chronic
      grief and how that impacts on parent-child bonding. There is evidence that our
      screening endeavors have far outstripped our habilitation efforts, leaving
      parents with a diagnosis but without support. This gap must be closed.

PMID- 14648816
TI  - Early amplification options.
AB  - Children with permanent hearing loss have been remediated with hearing
      amplification devices for decades. The influx of young infants identified with
      hearing loss through successful newborn hearing screening programs has
      established a need for amplification resources for infants within the first six
      months of life. For the approximately two of every 1000 infants born who are
      identified with bilateral hearing loss [Mehl and Thomson, 1998, Pediatrics 101,
      p. e4], the use of amplification is commonly the first step in treating the
      sequella of their loss. The use of hearing aids, combined with early
      intervention, has been shown to significantly improve the speech and language
      skills of young children with hearing loss [Yoshinaga-Itano, 2000, Seminars in
      Hearing 21, p. 309]. Speech and language delays have contributed to compromised
      academic performance of school aged children with hearing loss [Johnson et al.,
      1997, Educational Audiology Handbook, Singular Publishing, San Diego]. Most hard
      of-hearing and deaf children use hearing aids and other assistive listening
      devices every day throughout their lifetime and the life expectancy of a hearing
      aid is only five to eight years. The current challenge for pediatric audiologists
      is selecting and evaluating the available amplification to provide the best
      options for children and their families. Amplification technology has seen an
      explosion in growth the past few years and the options continue to expand
      rapidly. This article examines currently available amplification technology and
      reviews the selection criteria that may be used for infants and young children.
      Issues such as style, type, amplification features, signal processing strategies,
      and verification and validation tools are also discussed.

PMID- 14648817
TI  - Communication options for children with hearing loss.
AB  - This article examines the communication options that are available for use within
      families of infants and young children who are hard-of-hearing or deaf. The need
      for language development, regardless of the specific communication mode, is
      stressed. The demands of the current environment of early identification and
      intervention often put families in a position of needing to decide among
      communication methods before they are fully knowledgeable and/or emotionally
      ready. Specific communication options are delineated and considered within a
      continuum of spoken and visual language. Available research related to early
      acquisition of language by infants and young children who are hard-of-hearing and
      deaf is reviewed; outcomes, when available, are presented for specific methods
      from reports of older children. Factors that influence families' decisions
      regarding the selection of a communication option are highlighted in the context
      of the existing literature. An ongoing evaluative process that respects the
      choices of families is advocated; a context in which change(s) in communication
      mode through childhood is viewed as a positive circumstance. The ultimate goal in
      the selection of any communication approach is to ensure that infants and young
      children who are hard of hearing or deaf and their families are language
      proficient and fluent communicators.

PMID- 14648818
TI  - Early intervention after universal neonatal hearing screening: impact on
      outcomes.
AB  - This article summarizes the developmental outcomes of Colorado children with
      significant hearing loss. Some of the research compares children born in
      hospitals that have implemented universal newborn hearing screening programs for
      newborns. Other research compares the developmental outcomes of children who have
      been early-identified with hearing loss. Early-identification is defined as
      identification of hearing loss within the first six months of life. Late
      identification in the Colorado studies is defined as age of identification of
      hearing loss after the age of six months. In a few of the Colorado studies, age
      at initiation of intervention was used. Within the Colorado system, age of
      identification can be interpreted as almost synonymous with age of intervention,
      as the vast majority of children enter intervention services with two months
      after the identification of the hearing loss. Children who were early-identified
      and had early initiation of intervention services (within the first year of life)
      had significantly better vocabulary, general language abilities, speech
      intelligibility and phoneme repertoires, syntax as measured by mean length of
      utterance, social-emotional development, parental bonding, and parental grief
      resolution. Two other studies (Nebraska and Washington state) of early- versus
      later-initiation of intervention services report findings similar to the Colorado
      studies. Direct comparisons with the historical literature are not possible
      because the developmental delays of what would now be termed "later-identified"
      were too low to report developmental ages for the birth through five-year-old
      population.

PMID- 14648819
TI  - Cochlear implants in young children.
AB  - The cochlear implant is best characterized as a device that provides access to
      the sound environment. The device enables the hearing pathway to respond to
      environmental and speech sounds, providing informational cues from the
      surroundings and from others that may escape visual detection. As the
      developmental effects of a profound hearing loss are multiple, cochlear implants
      have been applied to ever younger children in an attempt to promote a more normal
      level of developmental learning through audition. In deafness, transducer
      elements of the inner ear fail to trigger auditory nerve afferent nerves in the
      presence of sound input. However, large reserves of afferent fibers exist even in
      the auditory nerve of a profoundly deaf patient. Furthermore, these nerve fibers
      retain the ability to respond to prosthetic activation. Through developmental
      learning in the early, formative years, auditory centers of the brain appear
      capable of processing information from the implant to provide speech
      comprehension and oral language development. Multichannel implants have replaced
      original single channel designs. multichannel devices enable larger percentages
      of recipients to recognize the spoken word without visual cues because they
      provide spectral information in addition to temporal and intensity cues. Testing
      under conditions of auditory (implant)-only input reveals significant open-set
      speech understanding capabilities in more than 75% of children after three years
      of device use. The benefit provided by implants may vary with a number of
      conditions including: hearing history, age of deafness onset, age at
      implantation, etiology of deafness, linguistic abilities, and the presence of a
      motivated system of support of oral language development. Patient variables
      should be given individual consideration in judging candidacy for a cochlear
      implant and in planning rehabilitative and education services after surgery and
      activation of the device.

PMID- 14648820
TI  - Multi-turn time-of-flight mass spectrometers with electrostatic sectors.
AB  - The mass resolution of a time-of-flight (TOF) mass spectrometer is directly
      proportional to its total flight pathlength. Multi-turn or multi-passage ion
      optical geometries are necessary to obtain fight distances of sufficient length
      within reasonable size limitations. We have investigated ion optics for a multi
      turn TOF mass spectrometer with electrostatic sectors. The concept of 'perfect'
      focusing conditions is introduced. Furthermore, a new type of multi-turn TOF mass
      spectrometer, the MULTUM Linear plus, was developed. It consists of four
      cylindrical electric sectors and 28 electric quadrupole lenses. It has a vacuum
      chamber 60 x 70 x 20 cm in size. Mass resolution is demonstrated to increase
      according to the number of ion cycles. A mass resolution of 350 000 (m/z = 28,
      FWHM) was achieved after 501.5 cycles. The MULTUM Linear plus analyzer is not
      simple, however; 28 electric quadrupole lenses are used. In order to reduce the
      number of ion optical parts, an improved multi-turn TOF mass spectrometer, the
      MULTUM II, consisting of only four toroidal electric sectors, was also developed.
      The possibility of tandem mass spectrometric applications using multi-turn TOF
      mass spectrometers is also discussed.

PMID- 14648821
TI  - Neutral loss of amino acid residues from protonated peptides in collision-induced
      dissociation generates N- or C-terminal sequence ladders.
AB  - The widespread occurrence of the neutral loss of one to six amino acid residues
      as neutral fragments from doubly protonated tryptic peptides is documented for 23
      peptides with individual sequences. Neutral loss of amino acids from the N
      terminus of doubly charged tryptic peptides results in doubly charged y-ions,
      forming a ladder-like series with the ions [M + 2H](2+) = y(max) (2+), y(max - 1)
      (2+), y(max - 2) (2+), etc. An internal residue such as histidine, proline,
      lysine or arginine appears to favor this type of fragmentation, although it was
      sometimes also observed for peptides without this structure. For doubly
      protonated non-tryptic peptides with one of these residues at or near the N
      terminus, we observed neutral loss from the C-terminus, resulting in a doubly
      charged b-type ion ladder. The analyses were performed by Q-TOF tandem mass
      spectrometry, facilitating the recognition of neutral loss ladders by their 2+
      charge state and the conversion of the observed mass differences into reliable
      sequence information. It is shown that the neutral loss of amino acid residues
      requires low collision offset values, a simple mechanistic explanation based on
      established fragmentation rules is proposed and the utility of this neutral loss
      fragmentation pathway as an additional source for dependable peptide sequence
      information is documented.

PMID- 14648822
TI  - Evaluation of the metal binding properties of a histidine-rich fusogenic peptide
      by electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry (ESI-FTICRMS) was used to investigate metal ion interactions of the
      18 amino acid peptide fragment B18 (LGLLLRHLRHHSNLLANI), derived from the
      membrane-associated protein bindin. The peptide sequence B18 represents the
      minimal membrane-binding motif of bindin and resembles a putative fusion peptide.
      The histidine-rich peptide has been shown to self-associate into distinct
      supramolecular structures, depending on the presence of Zn(2+) and Cu(2+). We
      examined the binding of B18 to the metal ions Cu(2+), Zn(2+), Mg(2+), Ca(2+),
      Mn(2+) and La(3+). For Cu(2+), we compared the metal binding affinities of the
      wild-type B18 peptide with those of its mutants in which one, two or three
      histidine residues have been replaced by serines. Upon titration of B18 with
      Cu(2+) ions, we found sequential binding of two Cu(2+) ions with dissociation
      constants of approximately 34 and approximately 725 micro M. Mutants of B18, in
      which one histidine residue is replaced by serine, still exhibit sequential
      binding of two copper ions with affinities for the first Cu(2+) ion comparable to
      that of wild-type B18 peptide, but with a greatly reduced affinity for the second
      Cu(2+) ion in mutants H112S and H113S. For mutants in which two histidines are
      replaced by serines, the affinity for the first Cu(2+) ion is reduced
      approximately 3-10 times in comparison with B18. The mutant in which all three
      histidine residues are replaced by serines exhibits an approximately 14-fold
      lower binding for the first Cu(2+) ion compared with B18. For the other metal
      ions under investigation (Zn(2+), Mg(2+), Ca(2+), Mn(2+) and La(3+)), a modest
      affinity to B18 was detected binding to the peptide in a 1 : 1 stoichiometry. Our
      results show a high affinity of the wild-type fusogenic peptide B18 for Cu(2+)
      ions whereas the Zn(2+) affinity was found to be comparable to that of other di-
      and trivalent metal ions.

PMID- 14648823
TI  - Detoxification of 4-hydroxynonenal (HNE) in keratinocytes: characterization of
      conjugated metabolites by liquid chromatography/electrospray ionization tandem
      mass spectrometry.
AB  - Keratinocytes are potential targets of lipid peroxidation products (alpha,beta
      unsaturated aldehydes) generated in the skin following UV exposure, among which
      the most abundant and toxic product is 4-hydroxy-trans-2,3-nonenal (HNE). The aim
      of this study was to investigate the ability of keratinocytes (NCTC2544 cell
      lines) to detoxify HNE, through characterization of metabolites, until now never
      demonstrated, using a combined analytical approach (liquid chromatography (LC)
      and liquid chromatography/mass spectrometry (LC/MS)). Incubation of cells with
      HNE (up to 200 micro M) was performed in order to evaluate the ability of the
      cells to detoxify this toxic aldehyde, and indicated that the cell viability was
      maintained under these conditions. LC analysis of the extracellular media from
      keratinocytes incubated with 100 micro M HNE shows a time-dependent decrease of
      HNE, disappearance from the medium within 2 h and concomitant formation of two
      unconjugated (phase I) metabolites, 4-hydroxy-2-nonenoic acid (HNA) and 1,4
      dihydroxy-2-nonene (DHN), which were both identified and quantified by LC and
      accounted for 48.8 +/- 4.6% of the HNE dose. Four additional metabolites were
      identified in the extracellular medium by reversed-phase LC coupled with
      electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) with positive and
      negative ion detection as Michael adducts (phase II metabolites), arising by the
      addition of the nucleophilic sulfur of glutathione (GSH) to the electrophilic C-3
      of HNE, followed by oxidation-reduction enzymatic processes. The GSH-HNE
      conjugates were (a) S-(4-hydroxynonanal-3-yl)glutathione, (b) S-(1,4-dihydroxy
      nonane-3-yl)glutathione, (c) S-(4-oxononanal-3-yl)glutathione and (d) S-(4-oxo
      nonan-1-ol-3-yl)glutathione, and accounted for 52.3 +/- 5.8% of the HNE dose (35
      nmol mg(-1) protein), as estimated indirectly by measuring the extent of cellular
      GSH consumption (18.7 +/- 1.8 nmol mg(-1) protein). The time course of HNE
      biotransformation was then determined by monitoring the formation of metabolites
      inside and outside the cell at different times after HNE addition (5-120 min). A
      time-dependent and almost linear formation inside the cell was observed for all
      the metabolites (plateau after 15 min of incubation), followed by a rapid decay
      and a concomitant increase in the extracellular medium (plateau of formation
      after 60 min). This confirms that HNE diffuses into the cell where is totally
      metabolized through phase I and phase II reactions to unreactive products, which
      are then exported outside the cell. This is the first demonstration that skin
      epidermal cells are able to detoxify the cytotoxic products of lipid
      peroxidation.

PMID- 14648824
TI  - Intramolecular electrophilic aromatic substitution in gas-phase-protonated
      difunctional compounds containing one or two arylmethyl groups.
AB  - A variety of dibenzyl esters and ethers undergo a rearrangement process upon
      isobutane chemical ionization and collision-induced dissociation of their MH(+)
      ions, whereby a new bond is formed between the two benzyl groups, giving rise to
      abundant [C(14)H(13)](+) (m/z 181) ions. This rearrangement has been explained as
      an intramolecular electrophilic substitution in the gas phase occurring in an ion
      neutral complex formed by the cleavage of one of the benzyl-oxygen bonds. A
      similar highly efficient intramolecular electrophilic substitution takes place in
      di-alpha- and beta-naphthylmethyl adipates affording m/z 281 [C(22)H(17)](+)
      ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An
      analogous efficient rearrangement occurs in benzyl alpha- and beta
      naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl alpha- and beta
      phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much
      less efficient in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl
      derivatives, even less in benzylisopropyl and benzylacetyl analogs, and it is
      absent in benzyltetrahydropyranyl derivatives. The distinctive behavior of the
      protonated difunctional benzyl derivatives is interpreted in terms of the energy
      requirements of the O-R bond heterolysis of the protonated functionalities, the
      ability of the neutral R' groups (non-dissociated from the oxygen atom) to play
      the role of the nucleophile in the intramolecular electrophilic substitution
      processes and the electrophilicity of the R(+) ions.

PMID- 14648825
TI  - Elucidation of the fragmentation pathways of azaspiracids, using electrospray
      ionisation, hydrogen/deuterium exchange, and multiple-stage mass spectrometry.
AB  - Collision-induced dissociation (CID) mass spectra were generated for azaspiracids
      using electrospray ionisation (ESI), and hydrogen/deuterium (H/D) exchange was
      used to ascertain the number and type of replaceable hydrogens in the three
      predominant azaspiracid toxins. H/D exchange was conveniently achieved using
      deuterated solvents for liquid chromatography (LC). Using ion-trap mass
      spectrometry, multiple-stage CID experiments (MS(n)) on the protonated and fully
      exchanged ions were performed to decipher characteristic fragmentation pathways.
      The precursor and product ions from azaspiracids lost up to five water molecules
      from different regions during MS(n) experiments and it was possible to
      distinguish between the water losses from different molecular regions. These
      studies confirmed that the first water-loss ion in the spectra of azaspiracids
      resulted from dehydration at the vicinal diol at C20-C21. Five MS dissociation
      pathways were identified that resulted from fragmentation of the carbon skeleton
      of azaspiracids producing nitrogen-containing ions. Two pathways, involving
      cleavage of the E-ring and C27-C28, gave ions that were found in all
      azaspiracids. Three pathways, A-ring, C-ring and C19-C20 cleavages, were useful
      for distinguishing between azaspiracid analogues. The same product ions from
      backbone fragmentation were also observed using hybrid quadrupole time-of-flight
      mass spectrometry (QqTOFMS). The fragmentation of the A-ring was the most facile
      and was exploited in the development of LC/MS(n) methods for the analysis of
      azaspiracids.

PMID- 14648826
TI  - A derivatization assay using gaschromatography/negative chemical ionization
      tandem mass spectrometry to quantify 3-nitrotyrosine in human plasma.
AB  - Endogenous free or protein-associated 3-nitrotyrosine (3-NT) has been proposed as
      a biomarker of in vivo oxidative damage caused by nitrating agents. Isotopic
      dilution assay gaschromatographic/mass spectrometric (GC/MS) techniques have been
      employed to measure endogenous 3-NT levels. However, the quantitative normal
      plasma values reported so far are inconsistent. The results vary between the
      assays; they may have been influenced by in vitro artifactual nitration of
      tyrosine to 3-NT. In this study, a simple and artifact-free derivatization method
      for quantifying the endogenous 3-NT content of biological samples by GC/negative
      chemical ionization MS/MS is presented. The method is based on reduction of the
      nitro group of the molecule by dithionite, heptafluorobutyric acylation and
      subsequent methyl derivatization, di-O-methyldi-N-heptafluorobutyryl being the
      major derivative. The results showed excellent GC and MS properties, such as low
      background and a favorable fragmentation pattern. Endogenous 3-NT was
      unequivocally quantified using collision-induced dissociation in the selected
      reaction monitoring mode, whereas co-elution of unknown compounds interfered in
      the selected-ion monitoring mode. We found that tyrosine was nitrated in the
      presence of nitrate anions and heptafluorobutyric anhydride, but the product
      appeared as a di-O-methylmono-N-heptafluorobutyryl derivative. Therefore,
      artifactually formed 3-NT did not contribute to the measured endogenous 3-NT
      level owing to its different derivative structure. The method was applied to
      determine endogenous 3-NT in human plasma and plasma proteins. A detection limit
      of 0.03 nM for (13)C(6)-labeled 3-NT in plasma samples was established and the
      response was linear over a concentration range of 0-50 nM (R(2) > 0.999). The
      endogenous free 3-NT level (mean +/- SD) in ultrafiltered plasma samples from 12
      healthy adults was 0.74 +/- 0.30 nM. The mean concentration of 3-NT in their
      plasma total proteins was 0.60 +/- 0.40 pmol mg(-1). Hence, the described method
      is selective, eliminates the problem of artifactual nitration and is feasible for
      the quantification of free and protein-associated 3-NT in biological samples such
      as plasma.

PMID- 14648827
TI  - Liquid chromatography/electrospray ionization tandem mass spectrometric screening
      and confirmation methods for beta2-agonists in human or equine urine.
AB  - Electrospray ionization (ESI) mass spectra of 19 common beta(2)-agonists were
      investigated in terms of fragmentation pattern and dissociation behavior of the
      analytes, proving the origin of fragment ions and indicating mechanisms of charge
      driven and charge-remote fragmentation. Based on these data, liquid
      chromatographic/ESI tandem mass spectrometric (LC/ESI-MS/MS) screening and
      confirmation methods were developed for doping control purposes. These procedures
      employ established sample preparation steps including either acidic or enzymatic
      hydrolysis, alkaline extraction and, in the case of equine urine specimens,
      acidic re-extraction of the analytes. In addition, a degradation product of
      formoterol caused by acidic hydrolysis during sample preparation could be
      identified and utilized as target compound in screening and also confirmation
      methods. The screening procedures cover 18 or 19beta(2)-agonists, the estimated
      limits of detection of which for equine and human urine samples vary between 2
      and 100 ng ml(-1) and between 2 and 50 ng ml(-1), respectively. A single LC/MS/MS
      analysis can be performed in 9 min.

PMID- 14648828
TI  - Post-source decay matrix-assisted laser desorption/ionization mass spectrometric
      study of peracetylated isoflavone glycosides cationized by protonation and with
      various metal ions.

PMID- 14648831
TI  - Current literature in mass spectrometry.

PMID- 14648829
TI  - Collision-induced fluorine atom migration in atmospheric pressure ionization mass
      spectrometry.

PMID- 14648833
TI  - An overview of Trink's scientific accomplishments.

PMID- 14648834
TI  - Trink, the man.

PMID- 14648836
TI  - Mouse muscle identity: the position-dependent and fast fiber-specific expression
      of a transgene in limb muscles is methylation-independent and cell-autonomous.
AB  - We previously characterised transgenic mice in which fast-muscle-specific
      regulatory sequences from the human aldolase A pM promoter drive the
      chloramphenicol acetyltransferase gene expression. Mutation of a NF1/MEF2 binding
      site (M2 motif) in this promoter does not affect fibre-type specificity of the
      transgene but modifies its expression in a subset of fast-twitch fibres at the
      limb level, preferentially affecting distal limb muscles. We investigated the
      molecular and cellular bases of this peculiar expression pattern that provided an
      adequate model to characterise the mechanisms responsible for muscle positional
      information. By direct electrotransfer of mutated M2 construct in adult muscle,
      we demonstrate that positional differences in mutated M2 transgene expression are
      not observed when the transgene is not integrated into chromatin. Also, this
      transgene expression pattern does not seem to be correlated with the extent of
      CpG methylation in its promoter sequence. Finally, we show that positional values
      reflected by CAT levels are maintained in primary cultures established from
      different adult limb muscles, as well as in heterotopically transplanted muscles.
      Our results suggest that mutation of the M2 site contributes to reveal a
      molecular memory of fibre fate that would be set up on pM promoter during
      development and persist into adulthood possibly through a chromatin imprint
      maintained in satellite cells associated with various limb muscles.

PMID- 14648837
TI  - Alternative promoters and polyadenylation regulate tissue-specific expression of
      Hemogen isoforms during hematopoiesis and spermatogenesis.
AB  - Hemogen is a nuclear protein encoded by HEMGN (also known as hemogen in mouse,
      EDAG in human and RP59 in rat). It is considered to be a hematopoiesis-specific
      gene that is expressed during the ontogeny of hematopoiesis. Herein, we
      characterize two distinct splicing variants of HEMGN mRNA with restricted
      expression to hematopoietic cells and to round spermatids in the testis,
      respectively. Expression of the testis-specific HEMGN mRNA (HEMGN-t) is
      developmentally regulated and is concurrent with the first wave of meiosis in
      prepuberal mice. Sequence analysis reveals that HEMGN-t and the hematopoietic
      HEMGN mRNA (HEMGN-h) share a common coding sequence with distinct 5' and 3'
      untranslated regions and that these two isoforms are transcribed from the same
      gene locus, HEMGN, through the use of alternative promoters and polyadenylation
      sites. Thus, HEMGN expression exemplifies a developmental regulatory mechanism by
      which the diversification of gene expression is achieved through using distinct
      regulatory sequences in different cell types. Moreover, the existence of a testis
      specific isoform of HEMGN suggests a role in spermatogenesis. Finally,
      fluorescence in situ hybridization demonstrates that HEMGN is localized to
      chromosome 4 A5-B2 in mouse and to chromosome 9q22 in human, which is a region
      known to harbor a cluster of leukemia breakpoints.

PMID- 14648838
TI  - DNA sequence motifs conserved in endocrine promoters are essential for Pax4
      expression.
AB  - The paired box transcription factor Pax4 is required for maturation of insulin
      producing beta- and somatostatin secreting delta-cells in the murine pancreas. It
      starts to be expressed in pancreatic precursors and later is restricted to beta-
      and delta-cells to finally be switched off after birth. A 0.9-kb genomic DNA
      fragment has been shown to mediate the Pax4 expression pattern. Transcription
      factors Pdx1 and NeuroD bind to this fragment at A2- and E1-sequence motifs. In
      this study, we downscale the size of this fragment to 409 bp. Another genomic
      fragment of 254 bp is still able to mediate the specificity, but not the strength
      of Pax4 expression. Deletion of the A2 and E1 elements results in loss or
      weakening of reporter gene expression. Because A2 and E1 elements are conserved
      in numerous pancreatic promoters, they might play a general role in regulating
      endocrine gene expression.

PMID- 14648839
TI  - Neurotrophin-3 signaling in mammalian Merkel cell development.
AB  - Merkel cells are sensory cells of neural crest origin. Because little is known
      about the mechanisms that direct their differentiation, we have investigated the
      potential role of a candidate regulatory factor, neurotrophin-3 (NT-3). At
      embryonic day 16.5 (E 16.5), neither NT-3 nor its primary receptors, TrkC and
      p75NTR are expressed by Merkel cells in the murine whisker. At the time of birth,
      however, Merkel cells are immunoreactive for NT-3, TrkC and p75NTR. In TrkC null
      and NT-3 null mice, Merkel cells differentiate initially, but undergo apoptosis
      perinatally. These results show that NT-3 signaling is not required for the
      differentiation of Merkel cells, but that it is essential for their postnatal
      survival.

PMID- 14648840
TI  - Thrombospondin-1-deficient mice exhibit increased vascular density during retinal
      vascular development and are less sensitive to hyperoxia-mediated vessel
      obliteration.
AB  - Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. Its expression is
      most prominent during the late stages of vascular development and in the adult
      vasculature. Our previous studies have shown that TSP1 expression promotes a
      quiescent, differentiated phenotype of vascular endothelial cells. However, the
      physiological role TSP1 plays during vascular development and neovascularization
      requires further delineation. Here, we investigated the role of TSP1 during
      development of retinal vasculature and retinal neovascularization during oxygen
      induced ischemic retinopathy. The retinal vascular density was increased in TSP1
      deficient (TSP1-/-) mice compared with wild-type mice. This finding was mainly
      attributed to increased number of retinal endothelial cells in TSP1-/- mice.
      During oxygen-induced ischemic retinopathy, the developing retinal vasculature of
      TSP1-/- mice was less sensitive to vessel obliteration induced by hyperoxia but
      exhibited a similar level of neovascularization induced by normoxia compared with
      wild-type mice. This finding is consistent with the similar pattern of VEGF
      expression detected in wild-type and TSP1-/- mice. Furthermore, the increased
      expression of TSP1 during development of retinal vasculature was not affected by
      oxygen-induced ischemic retinopathy. In addition, the regression of ocular
      embryonic (hyaloid) vessels, as well as the newly formed retinal vessels during
      oxygen-induced ischemic retinopathy, was delayed in TSP1-/- mice. Therefore, TSP1
      is a modulator of vascular homeostasis and its expression is essential for
      appropriate remodeling and maturation of retinal vasculature.

PMID- 14648841
TI  - Molecular markers of cardiac endocardial cushion development.
AB  - Endocardial cushions are precursors of mature heart valves. They form within the
      looped heart tube as discrete swellings and develop into thin, pliable leaflets
      that prevent regurgitation of blood. The embryonic origins of cardiac valves
      include endothelial, myocardial, and neural crest cells. Recently, an increasing
      number of animal models derived from mutational screens, gene inactivation, and
      transgenic studies have identified specific molecules required for normal
      development of the cardiac valves, and critical molecular pathways are beginning
      to emerge. To further this process, we have sought to assemble a diverse set of
      molecular markers encompassing all stages of cardiac valve development. Here, we
      provide a detailed comparative gene expression analysis of thirteen endocardial
      cushion markers. We identify endocardial cushion expression of the transcription
      factor Fog1, and we demonstrate active Wnt/beta-catenin signaling in developing
      endocardial cushions suggesting pathways that have not been previously
      appreciated to participate in cardiac valve formation.

PMID- 14648842
TI  - Role of Hertwig's epithelial root sheath cells in tooth root development.
AB  - During tooth development, after the completion of crown formation, the apical
      mesenchyme forms the developing periodontium while the inner and outer enamel
      epithelia fuse below the level of the crown cervical margin to produce a
      bilayered epithelial sheath termed Hertwig's epithelial root sheath (HERS). The
      role of HERS cells in root formation is widely accepted; however, the precise
      function of these cells remains controversial. Functions suggested have ranged
      from structural (subdivide the dental ectomesenchymal tissues into dental papilla
      and dental follicle), regulators of timing of root development, inducers of
      mesenchymal cell differentiation into odontoblasts and cementoblasts, to
      cementoblast cell precursors. The characterization of the HERS phenotype has been
      hindered by the small amount of tissue present at a given time during root
      formation. In this study, we report the establishment of an immortal HERS-derived
      cell line that can be maintained in culture and then induced to differentiate in
      vitro. Characterization of the HERS phenotype using reverse transcriptase
      polymerase chain reaction and Western blot immunostaining suggests that HERS
      cells initially synthesize and secrete some enamel-related proteins such as
      ameloblastin, and then these cells appear to change their morphology and produce
      a mineralized extracellular matrix resembling acellular cementum. These studies
      suggest that the acellular and cellular cementum are synthesized by two different
      types of cells, the first one by HERS-derived cementoblasts and the later by
      neural crest-derived cementoblasts.

PMID- 14648843
TI  - Generation of structures formed by lens and retinal cells differentiating from
      embryonic stem cells.
AB  - Embryonic stem cells have the potential to give rise to all cell lineages when
      introduced into the early embryo. They also give rise to a limited number of
      different cell types in vitro in specialized culture systems. In this study, we
      established a culture system in which a structure consisting of lens, neural
      retina, and pigmented retina was efficiently induced from embryonic stem cells.
      Refractile cell masses containing lens and neural retina were surrounded by
      retinal pigment epithelium layers and, thus, designated as eye-like structures.
      Developmental processes required for eye development appear to proceed in this
      culture system, because the formation of the eye-like structures depended on the
      expression of Pax6, a key transcription factor for eye development. The present
      culture system opens up the possibility of examining early stages of eye
      development and also of producing cells for use in cellular therapy for various
      diseases of the eye.

PMID- 14648844
TI  - Left-right asymmetric morphogenesis in the Xenopus digestive system.
AB  - The morphogenetic mechanisms by which developing organs become left-right
      asymmetric entities are unknown. To investigate this issue, we compared the roles
      of the left and right sides of the Xenopus embryo during the development of
      anatomic asymmetries in the digestive system. Although both sides contribute
      equivalently to each of the individual digestive organs, during the initial
      looping of the primitive gut tube, the left side assumes concave topologies where
      the right side becomes convex. Of interest, the concave surfaces of the gut tube
      correlate with expression of the LR gene, Pitx2, and ectopic Pitx2 mRNA induces
      ectopic concavities in a localized manner. A morphometric comparison of the
      prospective concave and convex surfaces of the gut tube reveals striking
      disparities in their rate of elongation but no significant differences in cell
      proliferation. These results provide insight into the nature of symmetry-breaking
      morphogenetic events during left-right asymmetric organ development.

PMID- 14648845
TI  - Alk8 is required for neural crest cell formation and development of pharyngeal
      arch cartilages.
AB  - The type I TGFbeta family member receptor alk8 acts in bone morphogenetic protein
      (BMP) signaling pathways to establish dorsoventral patterning in the early
      zebrafish embryo. Here, we present evidence that alk8 is required for neural
      crest cell (NCC) formation and that alk8 signaling gradients direct the proper
      patterning of premigratory NCCs. We extend our previous functional studies of
      alk8 to demonstrate that ectopic expression of constitutively active and dominant
      negative Alk8, consistently results in more medially or laterally positioned
      premigratory NCCs, respectively. We also demonstrate that patterning defects in
      premigratory NCCs, induced by alk8 misexpression, correlate with subsequent
      defects in NCC-derived pharyngeal arch cartilages. Furthermore, an
      anteroposterior effect is revealed, where overexpression of Alk8 more severely
      affects anterior arch cartilages and decreased Alk8 activity more severely
      affects posterior arch cartilage formation. Ectopic expression studies of alk8
      are supported by analyses of zygotic and maternal-zygotic laf/alk8 mutants and of
      several BMP pathway mutants. Pharyngeal mesodermal and endodermal defects in
      laf/alk8 mutants suggest additional roles for alk8 in patterning of these
      tissues. Our results provide insight into alk8-mediated BMP signaling gradients
      and the establishment of premigratory NCC mediolateral positioning, and extend
      the model for BMP patterning of the neural crest to include that of NCC-derived
      pharyngeal arch cartilages.

PMID- 14648846
TI  - Function of RARgamma and RARalpha2 at the initiation of retinoid signaling is
      essential for avian embryo survival and for distinct events in cardiac
      morphogenesis.
AB  - Avian embryogenesis requires retinoid receptor activation by the vitamin A active
      form, retinoic acid (RA), during neurulation. We conducted loss-of-function
      analysis in quail embryos by nutritional deprivation of RA and by blocking
      generation of retinoid receptors. Here we identify a distinct role for RARalpha2
      in cardiac inflow tract morphogenesis and for RARgamma in cardiac left/right
      orientation and looping morphogenesis. Blocking normal embryos with antisense
      oligonucleotides to RARalpha2 or RXRalpha diminishes GATA-4 transcripts, while
      blocking RARgamma or RXRalpha diminishes nodal and Pitx2 transcripts; the
      expression of these genes in the heart forming region resembles that of the
      vitamin A-deficient embryo. Blocking the function of RARgamma, RARalpha2, and
      RXRalpha recapitulates the complete vitamin A-deficient phenotype. RARgamma is
      the most potent mediator of the retinoid signal at this time of development. Our
      studies provide strong evidence that critical RA-requiring developmental events
      in the early avian embryo are regulated by means of distinct retinoid receptor
      signaling pathways.

PMID- 14648847
TI  - Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish (Danio
      rerio) lens development.
AB  - Connexins (Cx), the protein units of gap junctions, play important roles in lens
      development and homeostasis. Here, we report the mRNA expression patterns of
      zebrafish Cx48.5, Cx44.1, Cx43 during lens development. The expression of all
      three connexins in the adult lens was first confirmed by reverse transcriptase
      polymerase chain reaction. By whole-mount in situ hybridization, we detected
      Cx48.5 expression throughout the lens, except the lateral lens epithelium, at 36
      hours postfertilization (hpf). The pattern remained the same at 2 days
      postfertilization (dpf). By 3 and 4 dpf, Cx48.5 expression was restricted to the
      differentiating lens fibers in the equatorial and medial regions. Cx44.1 was
      expressed in a similar manner as Cx48.5 from 36 hpf to 4 dpf. However, Cx44.1
      expression was also detected in the lens at 24 hpf. Cx43 expression was detected
      throughout the lens at 24 and 36 hpf but became restricted to the lateral
      epithelium at later stages.

PMID- 14648849
TI  - Cranial expression of class 3 secreted semaphorins and their neuropilin
      receptors.
AB  - The semaphorin family of chemorepellents and their receptors the neuropilins are
      implicated in a variety of cellular processes, including axon guidance and cell
      migration. Semaphorins may bind more than one neuropilin or a heterodimer of
      both, thus a detailed knowledge of their expression patterns may reveal possible
      cases of redundancy or mutual antagonism. To assess their involvement in cranial
      development, we cloned fragments of the chick orthologues of Sema3B and Sema3F.
      We then carried out mRNA in situ hybridisation of all six class 3 semaphorins and
      both neuropilins in the embryonic chick head. We present evidence for
      spatiotemporal regulation of these molecules in the brainstem and developing
      head, including the eye, ear, and branchial arches. These expression patterns
      provide a basis for functional analysis of semaphorins and neuropilins in the
      development of axon projections and the morphogenesis of cranial structures.

PMID- 14648848
TI  - Identification of BOIP, a novel cDNA highly expressed during spermatogenesis that
      encodes a protein interacting with the orange domain of the hairy-related
      transcription factor HRT1/Hey1 in Xenopus and mouse.
AB  - Hairy-related transcription factor (HRT/Hey) genes encode a novel subfamily of
      basic helix-loop-helix (bHLH) transcription factors related to the Drosophila
      hairy and Enhancer-of-split (E(spl)) and the mammalian HES proteins that function
      as downstream mediators of Notch signaling. Using the yeast two-hybrid approach,
      a previously uncharacterized protein was identified in Xenopus that interacts
      with XHRT1 (originally referred to as bc8), one member of the HRT/Hey subclass.
      This protein is evolutionarily conserved in chordates. It binds to sequences
      adjacent to the bHLH domain of XHRT1 known as the Orange domain and has been
      named bc8 Orange interacting protein (BOIP). BOIP shows a rather uniform
      subcellular localization and is recruited to the nucleus upon binding to XHRT1.
      In Xenopus, XBOIP mRNA is detected by RNase protection analysis throughout
      embryogenesis. In the adult, the strongest expression is detected in testis. In
      the mouse, high levels of BOIP mRNA are also found in adult testis. No expression
      is detected in the embryo and in any of the other adult organs tested. In situ
      hybridization revealed that BOIP transcripts were detected almost exclusively in
      round spermatids and that this expression overlaps with that of Hey1 (HRT1),
      which is expressed throughout spermatogenesis. In view of the importance of the
      Orange domain for HRT/Hey function, the newly identified BOIP proteins may serve
      as regulators specifically of HRT1/Hey1 activity.

PMID- 14648850
TI  - Cadherin-1, -2, and -11 expression and cadherin-2 function in the pectoral limb
      bud and fin of the developing zebrafish.
AB  - Cadherins are cell adhesion molecules that play important roles in development of
      a variety of organs, including the vertebrate limb. In this study, we analyze
      cadherin expression patterns in the embryonic zebrafish pectoral limb buds and
      larval pectoral fins by using both in situ hybridization and immunocytochemical
      methods. cadherin-1 is detected in the epidermis of the embryonic limb buds and
      the larval pectoral fins. Cadherin-2 is expressed in the pectoral limb bud
      mesenchyme and chondrogenic condensation. As development proceeds, cadherin-2
      expression is detected in newly differentiated pectoral fin endoskeleton, but its
      expression is greatly down-regulated in the fin endoskeleton of larval zebrafish.
      cadherin-11 is found in the basal region of the embryonic limb buds and in the
      proximal endoskeleton of the larval pectoral fins. Interfering with cadherin-2
      function using two specific antisense morpholino oligonucleotides disrupts
      formation of the chondrogenic condensation/endoskeleton, suggesting that cadherin
      2 is crucial for the normal development of the zebrafish pectoral fins.

PMID- 14648851
TI  - Expression of a novel homeobox gene Ehox in trophoblast stem cells and pharyngeal
      pouch endoderm.
AB  - Ehox is an X-linked paired like homeobox gene identified from a differentiating
      embryonic stem (ES) cell cDNA library and is expressed at low levels in the
      preimplantation blastocyst and in ES cells in vitro. In embryos at 6.5 days post
      coitum (dpc), Ehox expression was restricted to the extraembryonic ectoderm which
      correlates with high-level expression in cultures of trophoblast stem cells.
      Extraembryonic expression becomes further restricted to the chorion and by 15.5
      dpc Ehox is expressed in chorionic trophoblast of the labyrinth and
      spongiotrophoblast layers of the placenta. Ehox expression in the embryo proper
      first appears at 8.5 dpc in the anterior foregut endoderm and by 9.5 dpc is
      visible in pharyngeal pouches 2-4. By 10.5 dpc, Ehox expression becomes
      restricted to the ventral end of pouches 2 and 3. The data presented here is the
      first description of Ehox expression during embryogenesis and suggests a dual
      role for Ehox: (1) in trophoblast stem cells and compartments of the developing
      placenta, and (2) during development of the pharyngeal pouches, possibly
      delineating the area to become thymus.

PMID- 14648852
TI  - Skin-specific expression of ictacalcin, a homolog of the S100 genes, during
      zebrafish embryogenesis.
AB  - Full-length cDNA coding for the ictacalcin gene, a homolog of the S100 genes, was
      isolated in zebrafish and mapped on linkage group 16 using the LN54 radiation
      hybrid panel. The homology and phylogenetic analyses, based on the deduced amino
      acid sequences, showed the orthologous relationship of ictacalcin genes between
      zebrafish and other fish species. However, ictacalcin genes constitute an out
      group with respect to other members of the S100 gene family. This result supports
      the findings that fish ictacalcin genes are new members of the S100 gene family
      and may have evolved after the divergence of teleosts and tetrapods. The
      zebrafish ictacalcin gene was zygotically transcribed from 12 hours
      postfertilization onward and was stably expressed throughout adulthood. During
      zebrafish embryogenesis, the ictacalcin gene was specifically expressed in
      striated epidermal cells covering the entire embryo. The ictacalcin staining in
      keratinocytes of striated epithelia was absent in the cytoplasm surrounding the
      nuclei, but it was highly concentrated in the peripheral margin. Tissues enriched
      with epithelia folds, such as olfactory epithelium, hatching gland, pectoral fin
      buds, urogenital opening, and pharynx, showed a robust ictacalcin expression. The
      strikingly heavy staining of ictacalcin in the pharyngeal region provides us with
      an early marker to follow the pharynx formation in zebrafish embryos.

PMID- 14648853
TI  - Tetraploid development in the mouse.
AB  - Spontaneous duplication of the mammalian genome occurs in approximately 1% of
      fertilizations. Although one or more whole genome duplications are believed to
      have influenced vertebrate evolution, polyploidy of contemporary mammals is
      generally incompatible with normal development and function of all but a few
      tissues. The production of tetraploid (4n) embryos has become a common
      experimental manipulation in the mouse. Although development of tetraploid mice
      has generally not been observed beyond midgestation, tetraploid:diploid (4n:2n)
      chimeras are widely used as a method for rescuing extraembryonic defects. The
      tolerance of tissues to polyploidy appears to be dependent on genetic background.
      Indeed, the recent discovery of a naturally tetraploid rodent species suggests
      that, in rare genetic backgrounds, mammalian genome duplications may be
      compatible with the development of viable and fertile adults. Thus, the range of
      developmental potentials of tetraploid embryos remains in large part unexplored.
      Here, we review the biological consequences and experimental utility of
      tetraploid mammals, in particular the mouse.

PMID- 14648854
TI  - Roles of the Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis.
AB  - Although it is often presumed that the molecular pathways that underlie normal
      organogenesis are similar to those perturbed during carcinogenesis, few examples
      exist of tissue-specific regulatory genes that play central roles in both
      processes. In the case of the prostate gland, molecular genetic analyses have
      demonstrated that the Nkx3.1 homeobox gene plays an important role in normal
      differentiation of the prostatic epithelium and that its loss of function is an
      initiating event in prostate carcinogenesis. Thus, the Nkx3.1 homeobox gene
      provides a paradigm for understanding the relationship between normal
      differentiation and cancer, as well as a model for studying the roles of homeobox
      genes in these processes. Here, we review recent findings concerning the
      biological as well as biochemical function of this central regulator of prostate
      development and carcinogenesis.

PMID- 14648856
TI  - Rim versus sagittal mandibulectomy for the treatment of squamous cell carcinoma:
      two types of mandibular preservation.
AB  - BACKGROUND: The role of conservative mandibulectomy for patients with bone
      invasion from squamous cell carcinoma remains poorly defined. However, marginal
      mandibular resection is biomechanically secure in its design while maintaining
      the mandibular continuity. This procedure has proven to be a successful method of
      treating squamous cell carcinoma with limited mandibular involvement. PURPOSE:
      The purpose of this study was to analyze our results after the use of a marginal
      technique for the treatment of oral and oropharyngeal cancer and to compare two
      types of mandibular conservative procedures: rim resection versus sagittal inner
      mandibulectomy. METHODS: A retrospective review of a cohort of 50 patients
      (global group) who underwent mandibular conservative resection for previously
      untreated squamous cell carcinoma was performed. Two subgroups were considered:
      rim group (n = 37) and sagittal group (n = 13). Clinical evaluation and
      preoperative radiologic studies were the means used to evaluate bony invasion and
      to decide on the extent of mandibulectomy. The treatment outcome after these two
      types of mandibular resection was calculated and compared using analysis by the
      Pearson chi(2) test, logistic regression model for multivariate analysis, and the
      Kaplan-Meier method to determine survival. RESULTS.: In the sagittal group,
      specimens from 2 patients (11.7%) demonstrated tumor invasion on decalcified
      histologic examination, whereas the rim group showed 11 cases (29.7%) with bone
      invasion. Local recurrence was observed in the follow-up of 10 patients. No
      statistical relationship was found between the presence of histologic bone
      invasion and the risk of local recurrence. The size of bone resection >4 cm (p
      =.002) and tumor invasion of surgical margins (p =.039) were found to be
      associated with increased local recurrence rates. In multivariate analysis, lymph
      node affectation significantly correlated with histologic mandibular involvement
      (p =.02). In the global group, the 5-year observed survival rate was 56.97%.
      Overall survival and rate of recurrence were comparable in both groups. In the
      global group, tumor infiltration beyond the surgical margin was statistically
      related with poor survival (p =.01). CONCLUSIONS: Analysis of this series
      disclosed that marginal mandibulectomy is effective in the control of squamous
      cell carcinomas that are close to or involving the mandible. In carefully
      selected patients, sagittal bone resection seems to be as appropriate as rim
      resection in the local control of these tumors.

PMID- 14648857
TI  - Postradiotherapy surveillance practice for head and neck squamous cell carcinoma-
      too much for too little?
AB  - INTRODUCTION: Limited information is available regarding surveillance patterns
      after head and neck cancer radiotherapy. We cataloged follow-up for a specified
      patient cohort treated at three neighboring university, community, and Veterans
      Administration institutions. METHODS: One hundred fifteen patients were treated
      with curative intent between 1994-1998 with definitive or postoperative
      radiotherapy for newly diagnosed squamous cell carcinoma of the oral cavity,
      oropharynx, larynx, or hypopharynx. One hundred patients had continuous follow-up
      at their treating institution and were included for analysis. Median follow-up
      until disease recurrence or censorship was 28.5 months. RESULTS: Median follow-up
      frequency was 5.7 visits/year and was highly variable. Although visit frequency
      correlated with disease stage and the presence of high-risk disease features,
      this association was lost when patients with early recurrences were removed from
      analysis. Procedure and test utilization closely mirrored visit frequency,
      resulting in a wide range of estimated yearly charges (0-15,668 dollars/year;
      median, 1,772 dollars/year). Actuarial 3-year overall survival for the study
      group was 71%. Eighty-six percent (19 of 22) of potentially salvageable
      locoregional failures were discovered secondary to symptomatic complaint rather
      than by test results. Disease failure, whether detected by symptom or testing,
      predicted for poor survival (22% at 24 months after recurrence). CONCLUSIONS:
      Postradiotherapy surveillance for head and neck cancer is inconsistently pursued.
      A proven correlation between intensive follow-up and improved patient survival is
      lacking. Surveillance directed by patient symptoms should be investigated as an
      alternative approach.

PMID- 14648858
TI  - Vertical ramus osteotomy combined with a parasymphyseal mandibulotomy for
      improved access to the parapharyngeal space.
AB  - BACKGROUND: A number of procedures have been described that facilitate access to
      the parapharyngeal space. Their use may be limited because of restricted access
      or postoperative morbidity. METHODS: We describe the use of two mandibular
      osteotomies to greatly enhance the exposure of the parapharyngeal space, with
      possible access up to the skull base. RESULTS: We have performed this procedure
      in three cases with minimal postoperative morbidity and no neurologic deficit or
      occlusal disturbances. CONCLUSIONS: We have found that the osteotomies described
      provide far better exposure to this area than a single mandibular osteotomy
      alone. Furthermore, it avoids a facial scar.

PMID- 14648859
TI  - Depressive symptoms during and after radiotherapy for head and neck cancer.
AB  - BACKGROUND: Patients with head and neck cancer are extraordinarily susceptible to
      depressive traits. Thus, a general screening of these patients at their first
      admission to the ital is desirable. METHODS: From 1997-2001, 133 patients with
      head and neck tumors filled in the Self-Rating-Depression-Scale (SDS) at the
      beginning and end of radiotherapy (ti1/ti2), 6 weeks, and 6 months after
      radiotherapy (ti3/ti4). RESULTS.: The SDS index increased significantly from
      46.44 (ti1) to 48.91(ti2) (p =.025) and then remained stable. The subdomain
      "somatic-eating-related symptoms" at ti1 was significantly lower than ti2 (p
      <.001). In contrast to inpatients, outpatients and those with conventional
      instead of hyperfractionated-accelerated radiotherapy were less impaired by
      eating-related symptoms. Patients with higher education showed a lower SDS index
      and cognitive scale. Marital status, tumor stage, histologic grading, and
      substance abuse had no influence. CONCLUSIONS: Patients with a higher risk of
      depression should receive long-term monitoring during and after the end of
      radiotherapy, and prompt intervention strategies should be applied.

PMID- 14648860
TI  - Impact of comorbidity on the outcome of laryngeal squamous cancer.
AB  - BACKGROUND: Comorbidity has been shown to be a determinant in treatment selection
      and survival in various cancers. We have previously shown that the Adult
      Comorbidity Evaluation-27 index is applicable in a United Kingdom setting, and
      the process of comorbidity grading by retrospective notes evaluation is an
      accurate and reliable process. METHODS: The impact of comorbidity and other
      factors on survival was examined retrospectively in a cohort of 180 patients with
      laryngeal squamous cell cancer. RESULTS: This study shows for the first time that
      the higher comorbidity burden seen in supraglottic cancers in contrast to glottic
      tumors might account for the poorer prognosis. This study also externally
      validates the composite comorbidity-TNM staging system described by Piccirillo
      and shows the composite system to be a better predictor of outcome than TNM
      staging system alone. CONCLUSIONS: Moderate and severe comorbidity have a greater
      and statistically significant impact on survival than the TNM staging system.

PMID- 14648861
TI  - Carcinoma of the skin with perineural invasion.
AB  - PURPOSE: To evaluate the outcome and patterns of relapse in patients treated for
      skin carcinoma of the head and neck with either microscopic or clinical
      perineural invasion. METHODS AND MATERIALS: Radiotherapy alone or combined with
      surgery was used to treat 135 patients with microscopic or clinical evidence of
      perineural invasion of skin carcinoma. All patients had at least 2 years of
      follow-up. RESULTS: The 5-year local control rates without salvage therapy were
      87% with microscopic perineural invasion and 55% with clinical perineural
      invasion. Overall, 88% of the local failures occurred in patients with positive
      margins. Almost half of the recurrences in patients with microscopic perineural
      invasion were limited to the first-echelon regional nodes. However, only 1 of 11
      patients with basal cell carcinoma with microscopic perineural invasion had a
      nodal failure. Ninety percent of recurrences in patients with clinical perineural
      invasion occurred at the primary site. Cranial nerve deficits rarely improved
      after successful treatment of the primary disease. Radiographic abnormalities
      remained stable 30% of the time when patients had clinical evidence of
      progressive disease. CONCLUSIONS: Radiotherapy in patients with skin cancer with
      clinical perineural invasion should include treatment of the first-echelon
      regional lymphatics. The risk of regional node involvement is also relatively
      high for patients with squamous cell carcinoma with microscopic perineural
      invasion. In patients with clinical perineural invasion, the poor local control
      rates with conventional radiotherapy suggest a need for dose escalation with or
      without concomitant chemotherapy.

PMID- 14648862
TI  - Eating ability in head and neck cancer patients after treatment with
      chemoradiation: a 12-month follow-up study accounting for dropout.
AB  - BACKGROUND: Head and neck cancer patients treated with chemoradiation have
      difficulty eating a normal diet. This study was designed to characterize eating
      ability over 12 months after chemoradiation treatment. Analyses take patient
      dropout into account. METHODS: Two hundred fifty-five patients with head and neck
      cancer treated with chemoradiation were followed for 12 months. Eating ability
      was analyzed using generalized linear model methods that accounted for non
      ignorable dropout. RESULTS: Eating ability was compromised immediately after
      treatment and improved over 12 months to near pretreatment levels. Ability to eat
      at most 50% of the diet orally did not return to baseline levels (p <.05).
      However, the percent of patients eating a normal diet did return to baseline
      levels. Accounting for dropout modified the results, but the pattern of
      significance was similar. CONCLUSIONS: Treatment of head and neck cancer with
      chemoradiation has a significant effect on eating ability, which improves after
      12 months after treatment.

PMID- 14648863
TI  - Patient's response using freetext in the University of Washington Quality of Life
      Scale.
AB  - BACKGROUND: The University of Washington Quality of Life Scale is the only
      validated head-and-neck-specific questionnaire that invites patients to write
      comments in the form of freetext. Freetext allows the questionnaire to record
      issues raised by the patient. METHOD: Two hundred seventy-eight consecutive
      patients treated between 1995 and 1999 by primary surgery for oral and
      oropharyngeal squamous cell carcinoma completed the UWQOL. Freetext from these
      patients was independently assessed by the authors. RESULTS: Comments were made
      by 61% of patients at some time. Completion was independent of clinicodemographic
      characteristics. Comments were predominantly head and neck (39%) and medical
      (35%). In 55% of cases, the overall tone was negative. Around a quarter of issues
      was not part of a validated health-related quality-of-life questionnaire.
      CONCLUSIONS: Freetext gives the multidisciplinary team a better insight into the
      concerns of the patient and can be used to promote a holistic approach.

PMID- 14648864
TI  - Early glottic carcinoma: treatment according patient's preference?
AB  - BACKGROUND: To analyze the results in early (stage I and II) glottic carcinoma of
      a single institution with a patient-oriented concept. METHODS: After diagnostic
      workup and multidisciplinary counseling, either radiotherapy or CO(2) laser
      surgery was chosen with respect to the patient's preference. RESULTS: Sixty-five
      patients underwent laser surgery and 75 had radiotherapy. For T1 tumors, the 5
      year overall survival, disease-specific survival, and initial local control rate
      after laser surgery and radiotherapy were comparable (OS, 85% vs 88%; DSS, 96% vs
      93%; LCR, 86% vs 85%). In contrast, initial local control for T2 tumors was
      significantly more favorable after surgery (OS, 83% vs 78%; DSS, 83% vs 88%; LCR,
      89% vs 67%). Larynx preservation was significantly higher after surgery in T1
      tumors (96% vs 82%) and in T2 tumors (89% vs 77%). CONCLUSIONS: Selection of the
      treatment modality according to patient's preference results in a comparable
      control of disease for T1 tumors. The initial local control for T2 tumors is
      significantly better after surgery. In both stages laser surgery warrants a
      better larynx preservation rate.

PMID- 14648865
TI  - Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and
      radiochemotherapy: part 1, pathogenesis and prophylaxis of mucositis.
AB  - BACKGROUND: Oral mucositis is a common sequel of radiotherapy, chemotherapy, and
      radiochemotherapy in patients with cancer or patients requiring hemopoietic stem
      cell transplants. Mucositis has a direct and significant impact on the duration
      of disease remission and cure rates, because it is a cancer treatment-limiting
      toxicity. Mucositis also affects survival because of the risk of infection and
      has a significant impact on the quality of life and cost of care. METHODS: This
      article reviews publications on the etiopathogenesis and prevention of oral
      mucositis accessible from a MEDLINE search using as key words, mucositis,
      radiotherapy, chemotherapy, hemopoietic stem cell transplant, and oral.
      CONCLUSIONS: Of the current available products, ice chips and benzydamine have
      the strongest scientific evidence of support for prophylaxis of mucositis.

PMID- 14648866
TI  - Benign metastasizing pleomorphic adenoma of the parotid gland: a
      clinicopathologic puzzle.
AB  - BACKGROUND: Pleomorphic adenoma constitutes the most common benign parotid gland
      tumor. Local recurrence after surgical treatment (lateral or total parotidectomy)
      has been described in 1% to 5% of cases. Malignant degeneration has been reported
      in 2% to 9% of cases of pleomorphic adenoma of salivary gland origin.
      Metastasizing pleomorphic adenomas without histologic evidence of malignancy have
      rarely been reported. Metastatic lesions have been discovered in bone, lymph
      nodes, the lung, oral cavity, pharynx, skin, liver, retroperitoneum, kidney,
      calvarium, and central nervous system. To the best of our knowledge, we hereby
      report the first case of pleomorphic adenoma of the parotid gland metastasizing
      to the ipsilateral maxilla. METHODS: We simultaneously examined apoptosis-related
      protein expression and markers of cell-proliferation activity in our case of
      benign pleomorphic adenoma metastasis and compared outcome with a control group
      of primary parotid pleomorphic adenomas. RESULTS: Analysis of p53, Bcl-2, MIB1,
      CD 105, p27, and p21 expression did not reveal significant differences between
      metastasizing pleomorphic adenoma of the salivary gland and the control group of
      primary parotid pleomorphic adenomas. CONCLUSIONS: Clinical rather than
      pathologic evidence seems to justify inclusion of metastasizing salivary
      pleomorphic adenoma in the group of low-grade malignant salivary tumors.

PMID- 14648867
TI  - Sinonasal paraganglioma: endoscopic resection with a 4-year follow-up.
AB  - BACKGROUND: Paragangliomas are uncommon neuroendocrine tumors. In the head and
      neck, they are most commonly seen at the carotid body, the temporal bone, or
      along the vagus nerve. Sinonasal paragangliomas are extremely rare. Most cases
      reported describe management by open surgical resection, with sublabial and/or
      transfacial approaches. METHODS: We present a case of a large sinonasal
      paraganglioma successfully managed by endoscopic resection. RESULTS: The patient
      has no evidence of recurrence after 4 years of follow-up. CONCLUSIONS: This case
      demonstrates that sinonasal paragangliomas might be amenable to endoscopic
      resection. However, the most important priority to consider when selecting a
      surgical technique is whether adequate excision with clear margins can be
      obtained. Furthermore, because of the aggressive nature of these tumors,
      regardless of the surgical approach, long-term follow-up is recommended.

PMID- 14648868
TI  - The relationships between xerostomia and dysphagia after chemoradiation of head
      and neck cancer.

PMID- 14648870
TI  - Pleiotropic effects of Hoxa10 on the functional development of peri-implantation
      endometrium.
AB  - Hoxa10, a homeodomain transcription factor, is dynamically expressed in adult
      uterine endometrium where it is necessary for embryo implantation. Endometrial
      Hoxa10 expression is driven by estrogen and progesterone. High levels of
      endometrial Hoxa10 expression coincide with high progesterone levels and
      development of endometrial receptivity. Although, progesterone is sufficient for
      endometrial differentiation and implantation, the molecular mechanisms by which
      progesterone mediates endometrial receptivity are not known. To determine if
      Hoxa10 mediates the developmental effects of progesterone in the endometrial cell
      compartments, we performed in vivo uterine transfection using pcDNA3.1/Hoxa10 in
      estrogen-primed, ovariectomized mice and compared results to mice treated with
      progesterone. Additional control mice were treated with either estrogen alone or
      empty vector pcDNA3.1. By using ovariectomized mice, we were able to determine
      specific developmental effects resultant from Hoxa10 treatment and distinguish
      them from those mediated by the regulation of multiple endogenous genes
      (including Hoxa10) by ovarian progesterone. Treatment with either Hoxa10 or
      progesterone resulted in diminished uterine weight and increased expression of
      characteristic cell-type specific differentiation markers such as epithelial
      calcitonin and stromal prolactin, suggesting that Hoxa10 likely mediates
      progesterone induced functional differentiation of endometrial epithelium and
      stroma. However, progesterone treatment suppressed endometrial eosinophil
      infiltration and degranulation compared to that seen with Hoxa10 treatment.
      Besides mediating progestational effects, Hoxa10 may activate distinct
      developmental pathways leading to endometrial differentiation. Functional
      differentiation in regenerative adult tissues may depend on timed expression of
      embryonic selector genes. Mol. Reprod. Dev. 67: 8-14, 2004.

PMID- 14648869
TI  - Mouse RanBPM is a partner gene to a germline specific RNA helicase, mouse vasa
      homolog protein.
AB  - Germ cell-specific ATP-dependent RNA helicase, the product of the mouse vasa
      homolog (Mvh), has been shown to play an essential role in the development of the
      male germ cell. In male Mvh knockout mice, premeiotic germ cells arrest at the
      zygotene stage. To investigate the role of MVH protein in the progression of
      meiosis, we searched for genes encoding partners that interact with MVH in
      testicular germ cells. Using the yeast two-hybrid system, we found that MVH
      interacts with mouse RanBPM, a Ran-GTP binding protein involved in microtubule
      nucleation. RanBPM is predominantly expressed in the testis, especially in
      maturating spermatocytes. Within the cell, RanBPM and MVH are closely associated
      with perinuclear RNA-protein complexes and chromatoid bodies. The interaction of
      MVH with RanBPM points to a functional relationship between translational
      regulation and the microtubule nucleation during meiosis. Mol. Reprod. Dev. 66: 1
      7, 2004.

PMID- 14648871
TI  - Germ cell-less expression in medaka (Oryzias latipes).
AB  - The gene germ cell-less (gcl) plays an important role in the early
      differentiation of germ cells in Drosophila. We isolated the gcl homolog of the
      model teleost medaka (Oryzias latipes) using degenerated primers and an ovary
      cDNA bank. The predicted amino acid sequence of medaka gcl showed 92, 68 and 31%
      overall identity to mouse, human and Drosophila gcl respectively. RT-PCR revealed
      stronger expression in the ovary and weaker expression in testis, brain, heart,
      liver and muscle tissue. Expression in early embryos indicates the presence of
      maternal mRNA. By in situ hybridisation (ISH), gcl could not be detected in
      embryos. In contrast to vasa, ISH revealed expression of gcl in the ovary but not
      in the testis. Mol. Reprod. Dev. 67: 15-18, 2004.

PMID- 14648872
TI  - Toxicogenomic difference between diethylstilbestrol and 17beta-estradiol in mouse
      testicular gene expression by neonatal exposure.
AB  - In this study, we investigated the effects of neonatal exposure to exogenous
      estrogen (diethylstilbestrol: DES, 17beta-estradiol: E2) on testicular gene
      expressions. Male C57BL/6J mice, 1 day after birth, were subcutaneously injected
      with DES or E2 (3 micrograms/mouse/day) for 5 days, and then they were raised for
      8 weeks. In morphological observation of 8-week-old mice testes, spermatozoa were
      absent from many seminiferous tubules in DES-treated mice testes, but there was
      no change in E2-treated mice testes. Analysis of in-house cDNA microarray (mouse
      cDNA 889 genes) revealed that 17 genes were altered in DES-treated mice testes at
      8 weeks of age, compared to each control. Real-time reverse transcription
      polymerase chain reaction (real-time RT-PCR) analysis of these genes revealed
      that some genes, which were changed in E2-treated testis, were the same as in DES
      treated testis, whereas in other cases there was a difference between DES-treated
      and E2-treated testis. The present results suggest that each exogenous estrogenic
      compound has both a common gene expression change pattern and its own testicular
      gene expression change pattern. Mol. Reprod. Dev. 67: 19-25, 2004.

PMID- 14648873
TI  - Expression profiling of the developing testis in wild-type and Dazl knockout
      mice.
AB  - Genetic understanding of male-factor infertility requires knowledge of gene
      expression patterns associated with normal germ cell differentiation. The mouse
      is one of the best models of mammalian fertility due to its well-characterized
      genetics and the existence of many infertile mutants both naturally occurring and
      experimentally induced. We used cDNA microarrays firstly to investigate normal
      gene expression in the wild-type (wt) testis and secondly to gain a better
      insight into the effect of the disruption of the Dazl gene on spermatogenesis. We
      constructed a cDNA microarray from a subtracted and normalized adult testis
      library and focused on six developmental time-points during the initial
      synchronous wave of spermatogenesis. The results suggest that in the wild-type
      testis, 89.5% of genes on our chip change expression dramatically during the time
      course. To identify patterns in the gene-expression data, a k-means clustering
      algorithm and principal component analysis were used. In the Dazl knockout
      testes, the majority of genes remain at baseline levels of expression, because
      absence of Dazl has a severe effect on cell-types present in the testis. Although
      in the prepubescent Dazl-null mice the final point reached in germ cell
      development is the leptotene-zygotene stage, the microarray results suggest that
      lack of Dazl expression has a detectable effect on the mRNA complement of germ
      cells as early as day 5 when only type A spermatogonia are present. Mol. Reprod.
      Dev. 67: 26-54, 2004.

PMID- 14648874
TI  - A binding site for germ cell nuclear factor within c-mos regulatory sequences.
AB  - The proto-oncogene c-mos is specifically expressed in male and female germ cells.
      Previous studies have shown that the orphan nuclear receptor chicken ovalbumin
      upstream promoter transcription factor (COUP-TF) contributes to the repression of
      c-mos in somatic cells by binding to an inverted hexamer repeat within the c-mos
      regulatory region. In the present study, we demonstrate that another nuclear
      receptor superfamily member, germ cell nuclear factor (GCNF), binds to a sequence
      overlapping the c-mos COUP-TF binding site. Electrophoretic mobility shift assays
      with recombinant GCNF and both wild-type and mutant c-mos oligonucleotides
      demonstrated the binding of GCNF to an extended half site, CCAAGTTCA, which
      overlaps the first hexamer of the COUP-TF binding site. Transient transfection
      assays in NIH 3T3 cells further demonstrated that GCNF fused to a VP16 activation
      domain stimulated transcription from reporter constructs containing the c-mos
      GCNF binding site. Since GCNF is expressed in male and female germ cells at the
      same stages of development at which c-mos is transcribed, these results suggest
      that GCNF may serve as a regulator of c-mos transcription. Mol. Reprod. Dev. 67:
      55-64, 2004.

PMID- 14648875
TI  - Cryopreservation of Xenopus transgenic lines.
AB  - Xenopus laevis has been widely used for molecular, cellular, and developmental
      studies. With the development of the sperm-mediated transgenic method, it is now
      possible to study gene function during vertebrate development by using this
      popular model. On the other hand, like other animal species, it is labor
      intensive, and the maintenance of transgenic lines is expensive. In this article,
      we investigated the possibility of using sperm-cryopreservation as a means to
      preserve transgenic frog lines. We demonstrated that cryopreserved sperms are
      viable but not fertile under our in vitro fertilization (IVF) conditions.
      However, by microinjecting cryopreserved sperm nuclei, we successfully
      regenerated a transgenic line carrying a double promoter transgene construct,
      where the marker gene encoding the green fluorescent protein (GFP) is driven by
      the gamma-crystallin gene promoter and a gene of interest, encoding a fusion
      protein of GFP with the matrix metalloproteinase stromelysin-3 (ST3-GFP), is
      driven by a heat shock-inducible promoter. We demonstrated the functional
      transmission of the ST3-GFP transgene by analyzing the phenotype of the F1
      animals after heat-shock to induce its expression. Our method thus provides an
      inexpensive means to preserve transgenic frog lines and a convenient way for
      distribution of transgenic lines. Furthermore, the ease with which to microinject
      nuclei compared to the technically demanding transgenesis procedure with variable
      outcome should facilitate more laboratories to use transgenic Xenopus laevis for
      functional studies in vivo. Mol. Reprod. Dev. 67: 65-69, 2004.

PMID- 14648876
TI  - Comparison of bulk enucleation methods for porcine oocytes.
AB  - Cloning of mammalian oocytes requires that the recipient oocyte is enucleated to
      remove all genetic material associated with the chromosomes. The procedure
      currently used in most species requires careful micromanipulation of oocytes
      treated with cytochalasin B to prevent structural damage. Although functional,
      this procedure requires time and limits the number of oocytes available for
      cloning, and our ability to understand the mechanisms of nuclear reprogramming.
      Therefore, this study aimed at evaluating different procedures to enucleate large
      pools of oocytes in a time-efficient manner. Two different approaches were
      tested. The first approach involved centrifugation of zona-free oocytes through a
      percoll gradient to separate the portion containing the chromatin from the
      cytoplasmic portion. The second used etoposide to prevent chromatin segregation
      at first metaphase and resulting in the expulsion of all chromosomes in the polar
      body. Using the chemical approach an average enucleation rate of 39.4 +/- 7.5%
      was obtained, while the centrifugation approach resulted in an average
      enucleation rate of 66.9 +/- 6. In terms of time efficiency, the control
      manipulation method takes 0.11 min and the centrifugation took an average of 0.52
      min per oocyte. The MPF activity at the end of procedure was estimated through
      the measurement of H1 activity and as expected, the etoposide-cycloheximide
      treated oocytes had lower H1 activity which was restored by further incubation in
      the maturation medium for 5 hr while the centrifugation gave a nonsignificant
      intermediary result. In conclusion, the results presented suggest that both the
      chemical and the mechanical methods are usable alternatives to micromanipulation
      of oocytes to generate a large number of chromosome free cytoplasm for
      biochemical analysis. Mol. Reprod. Dev. 67: 70-76, 2004.

PMID- 14648877
TI  - Effects of heat shock on in vitro development and intracellular oxidative state
      of bovine preimplantation embryos.
AB  - We investigated the effects of heat shock on developmental competence of bovine
      embryos and intracellular oxidative state. After in vitro fertilization, embryos
      were exposed to heat shock at 41 degrees C for 6 hr on days 0, 2, 4, and 6,
      respectively. On day 2, cleavage rate was not significantly different in all
      groups. However, the percentage of embryos developing to blastocyst stage after
      exposure to heat shock on day 0 (18.8 +/- 4.3%) and day 2 (23.6 +/- 3.7%) were
      significantly decreased compared with control (37.5 +/- 4.0%), day 4 (40.0 +/-
      7.4%), and day 6 (38.1 +/- 2.0%). In addition, the total cell number of
      blastocysts was significantly decreased by heat shock on day 0 (107.5 +/- 6.6)
      and day 2 (112.8 +/- 5.7) compared with the control (143.2 +/- 9.4). To evaluate
      intracellular oxidative state by heat shock, embryos exposed to heat shock on
      days 0, 2, 4, and 6 were incubated with 2',7'-dichlorodihydrofluorescein
      diacetate (DCHFDA) and fluorescence of oxidized DCHFDA by reactive oxygen species
      (ROS) was detected under fluorescent microscope. The intensity of fluorescence
      was significantly increased when embryos were exposed to heat shock on days 0 and
      2. However, heat shock on day 4 and day 6 did not increase the fluorescence
      intensity. These results indicate that (1) heat shock to earlier stage embryos
      causes a decrease in development to blastocysts and cell proliferation and (2)
      the decrease in development by heat shock could be involved in an increase of
      intracellular oxidative stress. Mol. Reprod. Dev. 67: 77-82, 2004.

PMID- 14648878
TI  - Molecular study of mouse peri-implantation development using the in vitro culture
      of aggregated inner cell mass.
AB  - To study the mechanisms of mouse peri-implantation development, we explored the
      in vitro culture of the isolated inner cell mass (ICM) of the blastocyst. As
      previously reported, individually cultured ICM recapitulated several early
      embryological events, such as the formation of primitive endoderm, epiblast, and
      proamniotic cavity. However, we found that the timing and efficiency of these
      morphogenetic processes significantly varied among the ICM. Due to this
      unpredictability in developmental potential, individually cultured ICM may be
      unsuitable for further analysis. By contrast, we found that when five ICM were
      fused into a single mass, such aggregates (5x ICM) underwent efficient and
      synchronous morphogenesis. The synchronous nature of 5x ICM development was also
      demonstrated by the temporal and spatial pattern of apoptotic cell death. TUNEL
      assay showed that a number of the epiblast cells committed apoptosis in 48 hr of
      culture, which took place after primitive endoderm differentiation but prior to
      proamniotic cavity formation. In situ hybridization analysis showed that Oct4 was
      downregulated and alpha-fetoprotein was upregulated in the primitive endoderm of
      the cultured 5x ICM. In addition, RT-PCR analysis revealed the expression of
      various primitive endodermal genes, but not of extraembryonic ectodermal markers
      in the cultured 5x ICM. Taken together, we propose that the 5x ICM is a useful in
      vitro tool to study the mechanisms of peri-implantation development of the mouse
      embryo. Mol. Reprod. Dev. 67: 83-90, 2004.

PMID- 14648879
TI  - Isolation of highly pure and viable primordial germ cells from rainbow trout by
      GFP-dependent flow cytometry.
AB  - A highly pure and viable primordial germ cell (PGC) population appears to be an
      essential tool for establishing a cell line that can differentiate into a germ
      cell lineage and for studying the molecular biology and biochemistry of fish
      PGCs. Therefore, the aim of the present study was to establish a flow cytometric
      method for isolating highly pure and viable PGCs. As the material for PGC
      isolation, we used transgenic rainbow trout possessing the green fluorescent
      protein (GFP) gene driven by trout vasa-gene regulatory sequences (pvasa-GFP).
      Four independent transgenic strains were subjected to fluorescence microscopy and
      GFP-dependent flow cytometric analyses. We found that some of the pvasa-GFP
      transgenic strains exhibited ectopic background green fluorescence in the somatic
      cells aside from strong fluorescence in PGCs. Although flow cytometric analysis
      of genital ridge somatic cells in the four pvasa-GFP transgenic strains revealed
      a wide range of GFP intensities, we proved that somatic cell contamination of the
      GFP-positive cell population was markedly reduced if transgenic strains without
      the ectopic background green fluorescence were used. In addition, the forward
      light-scattering (FS) property, which is an indication of relative cell size, and
      the side light-scattering (SS) property, which is determined by cell shape and
      granularity, were employed to remove non-PGC contaminants from the GFP-positive
      cell population. By isolating GFP-positive cells with high FS/SS values, we were
      able to effectively remove cell blebs and the apoptotic fraction. Consequently,
      the purities and survival rates of isolated PGCs were greatly improved compared
      with those using GFP intensity as a single indicator. Thus, our flow cytometric
      method, in combination with the selection of suitable transgenic strains without
      the ectopic background green fluorescence, is capable of isolating highly pure
      and viable PGCs from rainbow trout. By using this method in combination with cell
      cryopreservation and cell transplantation techniques, the isolated PGCs may also
      be used for preserving the genetic resources of endangered fish species and
      domesticated fish strains carrying commercially valuable traits. Mol. Reprod.
      Dev. 67: 91-100, 2004.

PMID- 14648880
TI  - alpha and beta spectrin distribution during the differentiation of pyriform cells
      in follicles of lizard Podarcis sicula.
AB  - Using alpha and beta spectrin mammalian antibodies on Western blotting, we
      demonstrated that lizard ovarian follicles contain two isoforms of alpha
      spectrin, Mr 94 and 134 kDa, and a 230 kDa beta spectrin, and that their pattern
      modifies in relation to pyriform cell differentiation. In fact, a positive
      immunoreaction is firstly evident within follicular epithelium of previtellogenic
      follicles when small cells differentiate into pyriform cells via intermediate
      cells. Later on, immunostain is present in pyriform cells and in the oocyte
      cortex that previously appears unstained. It is noteworthy that immunostain is
      also present on small cells located in contact with the oocyte membrane, but not
      on those located under the basal lamina and among pyriform cells, not engaged in
      pyriform cell differentiation. During the subsequent stages of previtellogenic
      phase, spectrin immunostain over the follicular epithelium and in the oocyte
      cortex does not change. By contrast, in vitellogenic follicles, when the
      follicular epithelium is constituted only by small cells, immunostain is evident
      at the level of the oocyte cortex and the cytoplasm of regressing pyriform cells.
      The present data strongly suggest that the alpha and beta spectrin pattern put in
      evidence during the different phases of lizard oocyte growth is related to the
      differentiation of small into pyriform cells, where such protein may guarantee a
      relationship between surface glycoproteins (Andreuccetti et al., 2001: Anat Rec
      263:1-9), and the cytoskeleton distribution (Maurizii et al., 2000: Raf Mol
      Reprod Dev 57:159-166). Furthermore, the distribution of spectrin mRNA, similar
      to that observed for the protein, demonstrates that spectrin, once synthesized
      within pyriform cells, is transferred through intercellular bridges in the oocyte
      cortex, thus confirming that pyriform cells are nurse that significantly are
      involved in the oocyte growth. Finally, the present data demonstrate that alpha
      spectrin of lizard ovarian follicles has Mr quite different from those so far
      reported and may constitute a new group of isoforms. This important result will
      be the focus of future experiments. Mol. Reprod. Dev. 67: 101-107, 2004.

PMID- 14648881
TI  - Sexing river buffalo (Bubalus bubalis L.), sheep (Ovis aries L.), goat (Capra
      hircus L.), and cattle spermatozoa by double color FISH using bovine (Bos taurus
      L.) X- and Y-painting probes.
AB  - River buffalo, sheep, and goat spermatozoa were cross-hybridized using double
      color fluorescence in situ hybridization (FISH) with bovine Xcen- and Y
      chromosome painting probes, prepared by DOP-PCR of laser-microdissected
      catapulted chromosomes, to investigate the possibility of using bovine probes for
      sexing sperm of other members of the family Bovidae. Before sperm analysis, the
      probes were hybridized on metaphase chromosomes of each species, as control.
      Frozen-thawed spermatozoa of cattle, river buffalo, sheep, and goat were
      decondensed in suspension with 5 mM DTT. Sperm samples obtained from three
      individuals of each species were investigated, more than 1,000 spermatozoa were
      scored in each animal. FISH analysis of more than 12,000 sperm revealed high
      level of sperm with X- or Y-signals in all of the species investigated,
      indicating FISH efficiency over 99%. Significant interspecific differences were
      detected in the frequency of aberrant spermatozoa (aneuploid and diploid) between
      goat (0.393%) and sheep (0.033%) (P < 0.01), goat and cattle (0.096%) (P < 0.5),
      as well as between river buffalo (0.224%) and sheep (P < 0.5). There was no
      significant difference between river buffalo and cattle. The present study
      demonstrated that it is possible to use bovine X-Y painting probes for sexing and
      analyzing sperm of other species of the family, thus facilitating future studies
      on the incidence of chromosome abnormalities in sperm as well as on sex
      predetermination of embryos for the livestock industry. Mol. Reprod. Dev. 67: 108
      115, 2004.

PMID- 14648882
TI  - Tesmin transcription is regulated differently during male and female meiosis.
AB  - Tesmin is a protein with homology to the metal-binding motif of the
      metallothionein protein family. Tesmin has been described as a testis-specific
      transcript, which starts to accumulate in 8-day-old mouse spermatocytes. Herein,
      a differential display comparing meiotic gene expression in embryonic ovaries and
      mature testes also revealed the presence of the Tesmin transcript in fetal
      ovaries as well as in fetal and adult heart. Time-course experiments showed that
      Tesmin was expressed in a characteristic development-related manner in fetal
      ovaries. Only a weak expression was observed at E12(1/2), the strongest signal
      was reached at E14(1/2), whereas the signal declined between E14(1/2) and
      E16(1/2). This transitional expression coincides with the early stages of the
      female meiotic prophase I. In the male, however, Tesmin was expressed in all
      stages of meiotic prophase I except preleptonema and leptonema. In situ
      hybridization further showed that the mRNA level increased during prophase I in
      the male, with the strongest expression seen at the transition from mid- to late
      pachytema (Stage VII-VIII). Furthermore, initiation of Tesmin transcription
      paralleled that of the synaptonemal complex protein 1 transcript (Scp1) in the
      fetal ovary and prepubertal testis. We, therefore, propose that Tesmin is likely
      to have a function in both the male and female meiotic prophase I. Moreover, the
      distinct difference in both the timing and the level of mRNA accumulation in the
      two gender's meiotic prophase I suggests that Tesmin transcription may be
      controlled by two different mechanisms during male and female meiosis. Mol.
      Reprod. Dev. 67: 116-126, 2004.

PMID- 14648883
TI  - Evaluation of two-dimensional L-COSY and JPRESS using a 3 T MRI scanner: from
      phantoms to human brain in vivo.
AB  - Localized versions of two-dimensional (2D) magnetic resonance spectroscopic (MRS)
      sequences, namely JPRESS and L-COSY, have been implemented on a whole-body 3T
      MRI/MRS scanner. Volume selection was achieved using three slice-selective radio
      frequency (RF) pulses: 90 degrees-180 degrees-180 degrees in JPRESS and 90
      degrees-180 degrees-90 degrees in L-COSY with a CHESS sequence prior to voxel
      localization for global water suppression. The last 180 degrees RF pulse was used
      for resolving the J-coupled cross peaks in JPRESS, whereas the last 90 degrees RF
      pulse was used for coherence transfer between J-coupled metabolites in L-COSY. A
      head MRI coil for 'transmission' and a 4 inch receive surface coil for
      'reception' or a head coil transmit/receive were used. A total of 16 healthy
      volunteers were investigated using these 2D MRS sequences. Voxel sizes of 18 and
      27 ml were localized in the occipito-parietal gray and white matter regions and
      the total duration for each 2D signal acquisition was typically 35 min. Compared
      with 2D L-COSY, reduced spectral width along the second spectral dimension and
      shorter 2D spectral acquisition were the major advantages of 2D JPRESS. In
      contrast, increased spectral width along the new spectral dimension in L-COSY
      resulted in an improved spectral dispersion enabling the detection of several
      brain metabolites at low concentrations that have not been resolved using the
      conventional one-dimensional (1D) MRS techniques. Due to increased sampling rate,
      severe loss of metabolite signals due to T2 during t1 was a major drawback of 2D
      JPRESS in vivo.

PMID- 14648884
TI  - Three-dimensional MRI of cerebral projections in rat brain in vivo after
      intracortical injection of MnCl2.
AB  - In this study we investigated the potential of in vivo MRI detection of axonal
      Mn2+ transport for tracing neuronal projections originating in the sensorimotor
      cortex in healthy and lesioned rat brains. Special attention was given to the
      potential of visualizing neuronal sprouting of central nervous system across the
      midline. After injecting unchelated MnCl2 into the forelimb area of sensorimotor
      cortex of 18 healthy and 10 lesioned rats corticofugal projections could be
      traced through the internal capsule to the cerebral peduncle and the pyramidal
      decussation. Although the neuronal tract was visible as early as 6 h after MnCl2
      injection, best contrast was achieved after 24-48 h. Beside the cortico-spinal
      tract, the cortico-thalamic fibres were also visualized by anterograde Mn2+
      transport. Cortico-striatal fibres were partially masked by the very high signal
      near the MnCl2 injection site but could be discerned as well. Slight, diffuse
      signal enhancement of cortical tissue contralateral to the MnCl2 injection site
      in healthy rat brains suggests interhemispheric connections or passive diffusion
      of Mn2+. However, enhanced fibre tract contrast connecting both hemispheres was
      visible 16 weeks after onset of focal photothrombotic cortical injury. In
      conclusion our study has shown that we were able to visualize reproducibly the
      main descending corticofugal projections and interhemispheric connections by non
      invasive MRI after localized injection of MnCl2. The appearance of
      interhemispheric Mn2+-enhanced fibres after photothrombotic focal injury
      indicates that the method may bear potential to follow non-invasively gross
      plastic changes of connectivity in the brain after injury.

PMID- 14648885
TI  - Absolute eigenvalue diffusion tensor analysis for human brain maturation.
AB  - The absolute eigenvalues of the diffusion tensor of white matter in sixteen
      normal subjects in two groups representing the early developmental stage (ages 1
      10 years, n=8) and young adult stage (ages 18-34 years, n=8) were assessed using
      a high-field (3.0 T) magnetic resonance (MR) system. All three eigenvalues,
      including the largest eigenvalue, decreased significantly with brain maturation.
      The rate of the decline in the two small eigenvalues was, however, much higher
      than that of the largest eigenvalue, resulting in an actual increase in
      fractional anisotropy, a commonly measured relative index. The data demonstrate
      that an increase in anisotropy associated with brain maturation represents a
      significant decline in the small eigenvalue components, rather than an increase
      in the largest eigenvalue. The observed pattern of eigenvalue changes is best
      explained by the simultaneous occurrence of two of several independent phenomena
      within the axonal microenvironment during the myelination process, namely, (1)
      decline in unrestricted water content in extra-axonal space, and (2) increase in
      apparent diffusivity within the axon.

PMID- 14648887
TI  - REST-PEEP: reduced scan time phase-encoded echo planar imaging.
AB  - Echo planar methodology can be used for rapid acquisition in three dimensions of
      k-space. There are two groups of sequences which have thus far been implemented.
      The first group is characterized by three-dimensional acquisition from a single
      RF excitation. Echo planar shift mapping and echo volume imaging are single-shot
      chemical shift imaging and three-dimensional spatial imaging techniques,
      respectively. Even though these methods are extremely fast, their spatial and
      spectral resolutions are poor. In the second group of sequences, echo planar
      imaging acquisition is repeated for every phase-encode gradient step to improve
      upon the spatial resolution and signal-to-noise ratio at the expense of
      acquisition time. Here we report a novel combination of these two groups of
      sequences aimed at providing additional flexibility in trade-offs between the
      spectral bandwidth, signal-to-noise ratio, spatial resolution and imaging time.
      Preliminary results for both chemical shift imaging and three-dimensional spatial
      imaging are presented. The chemical shift imaging was optimized for excitation of
      the N-acetyl aspartate (NAA). An interesting consequence of our approach is that
      the Nyquist ghost is transferred from the spectrum to the metabolite image.

PMID- 14648886
TI  - Baseline physiological state and the fMRI-BOLD signal response to apnea in
      anesthetized rats.
AB  - To decipher the biophysical mechanism behind the fMRI-BOLD response to apnea and
      its dependence on the baseline cerebral blood flow and oxygenation, fMRI and
      laser Doppler flow (LDF) studies were carried out in anesthetized rats. Baseline
      cerebral blood flow (CBF) and PaO2 were modulated by ventilating with different
      gas mixtures namely, room air (21% O2), 100% O2, carbogen (95% O2+5% CO2), 2% CO2
      in air or 5% CO2 in air, respectively. A decrease in BOLD signal intensity was
      observed after the onset of apnea with either room air, 2% CO2 or 5% CO2
      ventilation. PaO2 and cerebral tissue PO2 decreased during apnea under these
      conditions. However, the apnea-induced BOLD signal intensity was unaffected with
      carbogen ventilation and increased with 100% O2 ventilation, during which PaO2
      remained constant and cerebral tissue PO2 increased. When baseline CBF was high
      during hypercapnia, a faster decrease occurred in the apnea-induced BOLD signal.
      Apnea induced the largest increase in CBF of 85 +/- 25% when ventilated with 2%
      CO2 while a 44 +/- 8% increase was observed with room air. During the other
      ventilatory conditions, minimal or no significant change in CBF was observed
      during apnea. These results show a significant correlation between the BOLD
      signal change and tissue PO2 in response to apnea under different physiological
      conditions. Apnea-induced increase in CBF affects the magnitude of the BOLD
      signal response when PaO2 remains constant or changes minimally.

PMID- 14648888
TI  - On the use of R1 and R2* for measurement of contrast agent concentration in
      isolated perfused rat liver.
AB  - We present experimental MRI protocols at 4.7 T for quantitative determination of
      the Dotarem distribution volume in isolated perfused rat liver. The procedures
      involved either constant contrast agent (CA) concentration or bolus
      administration conditions. R1 and R2* effects of the CA in liver and perfusate
      were measured using gradient echo fast imaging (GEFI) experiments by varying
      either the excitation angle or the echo time. CA concentrations in liver and
      perfusate were also measured after MRI by inductively coupled plasma atomic
      emission spectroscopy, in order to determine in situ relaxivities in the
      perfusate (r1=4.2 +/- 0.1 s(-1) mm(-1), r2*=17 +/- 2 s(-1) mm(-1)) and in the
      liver (r1=7.2 +/- 0.2 s(-1) mm(-1), r2*=99 +/- 5 s(-1) mm(-1)). When CA
      concentrations were estimated from R1 measurements and r1, the CA distribution
      volume estimations in liver resulting from bolus (0.31 +/- 0.01) and stationary
      (0.32 +/- 0.05) experiments were not significantly different. In contrast, after
      a bolus, CA concentrations derived from R2* and r2* were overestimated in liver
      and even more in perfusate. However, with R1 and R2* being measured before CA
      bolus administration, zero echo time signal intensities computed from multiple TE
      measurements during multiple boli yielded good estimations of R1 and thus correct
      CA concentrations in liver and in perfusate. Under these conditions, a single
      multi-echo GEFI acquisition should be sufficient to determine the concentration
      time curves. Consequently, this protocol should be appropriate to rapidly
      estimate the distribution volume in vivo when multiple boli have to be avoided.

PMID- 14648889
TI  - Saturation-corrected T 1 and T 2 relaxation times of choline, creatine and N
      acetyl aspartate in human cerebral white matter at 1.5 T.

PMID- 14648892
TI  - The potential use of continuous-flow isotope-ratio mass spectrometry as a tool in
      forensic soil analysis: a preliminary report.
AB  - The use of continuous-flow isotope-ratio mass spectrometry (CF-IRMS) as a tool in
      soil analysis has been assessed as part of a larger study using a number of
      geological techniques applied in a forensic context. Carbon and nitrogen isotopic
      ratios, delta13C and delta15N, have been analysed to investigate situations which
      have arisen from crime casework. Three questions have been addressed: the role of
      spatial variation found over the short-scale (less than 20 m), temporal variation
      over a period of almost 2 years, and the variation found between source soils and
      soil transferred to footwear soles during a simple one-stage transfer process.
      Results are presented for the three experiments. The use of carbon and nitrogen
      isotopes has been shown to be useful in discriminating between soil types and
      sample locations, even when sampling occurs at a different time (as might be the
      case with a crime scene). In cases of primary transfer (from a source soil by a
      one-stage transfer to another surface, in this case, shoes and boots), the
      combination of carbon and nitrogen isotope ratios is a valuable tool in
      discriminating between sites and in showing the relationship of the transferred
      samples to the relevant source soils. Used in combination with other analytical
      techniques, isotopic analysis may prove to be a useful tool in a forensic
      context.

PMID- 14648893
TI  - Quantification of priming and CO2 respiration sources following slurry-C
      incorporation into two grassland soils with different C content.
AB  - The fate of incorporated slurry-C was examined in a laboratory experiment using
      two UK grassland soils, i.e. a Pelostagnogley (5.1 %C) and a Brown Earth (2.3
      %C). C3 and C4 slurries were incorporated into these two wet-sieved (C3) soils
      (from 4-10 cm depth). Gas samples were collected 0.2, 1, 2, 3, 4, 6, 9, 20, 30
      and 40 days after slurry application and analyzed for CO2 concentration and
      delta13C content. Slurry incorporation into the soil strongly increased soil CO2
      respiration compared with the unamended soil. Total (40 day) cumulative CO2 flux
      was higher for the Pelostagnogley than the Brown Earth. The 13C natural abundance
      tracer technique enabled quantification of the sources of respired CO2 and
      priming effects (days 0-9). Proportionally more slurry-derived C was respired
      from the Pelostagnogley (46%) than the Brown Earth (36%). The incorporated slurry
      C was lost twice as fast as the native soil C in both soils. Slurry incorporation
      induced a priming effect, i.e. additional release of soil-derived C, most
      pronounced in the Pelostagnogley (highest C content). The majority of respired
      soil-derived C (>70%) was primed C. The study indicated that potential reductions
      in ammonia volatilisation following slurry injection to grasslands might be
      negated by enhanced loss of primed soil C (i.e. pollution swapping).

PMID- 14648894
TI  - Relationship between soil organic C degradability and the evolution of the
      delta13C signature in profiles under permanent grassland.
AB  - The main objective of this research was to investigate to what extent the
      potential C dynamics of soil organic matter (SOM) are related to the degree of
      13C enrichment with increasing depth in soil profiles under permanent grassland.
      The evolution of the C content and the 13C natural abundance (delta13C value) of
      SOM were investigated in three soil profiles (0-40 cm depth) under permanent
      grassland of varying texture (a loamy sand, a loam and a clay loam soil). The
      delta13C value of the SOM showed a gradual increase with increasing depth and
      decreasing C content in the profiles, ranging from 1.9 per thousand (loamy sand
      soil), 2.9 per thousand (clay loam soil) and 4 per thousand (loam soil) in
      relation to the delta13C value of SOM at the surface. The relationship between
      the 13C enrichment and total organic C content at different depths in the
      profiles (down to 40 cm depth in the loam and clay loam soil, down to 25 cm depth
      in the loamy sand soil) could be well described by the Rayleigh equation. The
      enrichment factors epsilon, associated with the Rayleigh approximation of the
      data, ranged from -1.57 per thousand (clay loam soil) to -1.64 per thousand
      (loamy sand soil) and -1.91 per thousand (loam soil). The potential C dynamics in
      four depth intervals from the profiles (0-10, 10-20, 20-30 and 30-40 cm depth)
      were determined by means of an incubation experiment. The C decomposition rate
      constants from the four sampling depths in the profiles showed a significant,
      positive correlation (y = 0.21x + 0.018, R(2) = 0.66, p < 0.005) with the
      corresponding Deltadelta13C values (change of the delta13C value per depth
      increment). A better correlation was obtained when only the data from the upper
      20 cm in the profiles (y = 0.21x + 0.019, R(2) = 0.78, p < 0.05) were considered.
      These results suggest that the Deltadelta13C values in the surface layers of
      profiles under permanent grassland may serve as an indicator of the potential
      degradability or the stability of the SOM (in terms of C decomposition rate
      constants).

PMID- 14648895
TI  - Quantifying nitrate retention processes in a riparian buffer zone using the
      natural abundance of 15N in NO3-.
AB  - Quantifying the relative importance of denitrification and plant uptake to
      groundwater nitrate retention in riparian zones may lead to methods optimising
      the construction of riparian zones for water pollution control. The natural
      abundance of 15N in NO3- has been shown to be an interesting tool for providing
      insights into the NO3- retention processes occurring in riparian zones. In this
      study, 15N isotope fractionation (variation in delta15N of the residual NO3-) due
      to denitrification and due to plant uptake was measured in anaerobic soil
      slurries at different temperatures (5, 10 and 15 degrees C) and in hydroponic
      systems with different plant species (Lolium perenne L., Urtica dioica L. and
      Epilobium hirsutum L.). It was found that temperature had no significant effect
      on isotope fractionation during denitrification, which resulted in a 15N
      enrichment factor epsilonD of -22.5 +/- 0.6 per thousand. On the other hand,
      nitrate uptake by plants resulted in 15N isotope fractionation, but was
      independent of plant species, leading to a 15N enrichment factor epsilonP of -4.4
      +/- 0.3 per thousand. By relating these two laboratory-defined enrichment factors
      to a field enrichment factor for groundwater nitrate retention during the growing
      season (epsilonR = -15.5 +/- 1.0 per thousand ), the contribution of
      denitrification and plant uptake to groundwater nitrate retention could be
      calculated. The relative importance of denitrification and plant uptake to
      groundwater nitrate retention in the riparian buffer zone was 49 and 51% during
      spring, 53 and 47% during summer, and 75 and 25% during autumn. During
      wintertime, high micropore dissolved organic carbon (DOC) concentrations and low
      redox potentials due to decomposition of the highly productive riparian
      vegetation probably resulted in a higher denitrification rate and favoured other
      nitrate retention processes such as nitrate immobilisation or dissimilatory
      nitrate reduction to ammonium (DNRA). This could have biased the 15N isotope
      fractionation and led to a low 15N enrichment factor for groundwater nitrate
      retention during wintertime (-6.2 +/- 0.9 per thousand ). In contradiction to
      what many other studies suggest, it is possible that due to plant decomposition
      during the winter period other nitrate transformation processes compete with
      denitrification.

PMID- 14648896
TI  - Effect of preparation and preservation procedures on carbon and nitrogen stable
      isotope determinations from zooplankton.
AB  - A literature survey of zooplankton stable isotope studies revealed
      inconsistencies between authors concerning (a) fixation and (b) allowance for gut
      clearance of zooplankton prior to delta13C and delta15N determinations. To
      address whether commonly used preservation techniques induce changes in stable
      isotope values, fresh lake zooplankton (control) were compared with preserved
      (ethanol, methanol, formaldehyde, gluteraldehyde, frozen and shock frozen)
      material. Differences of up to 1.1 per thousand for carbon and 1.5 per thousand
      for nitrogen isotopic signatures were found. Even freezing, the most frequently
      used method identified from the literature, caused significant changes compared
      with the control. We advocate the use of fresh material prepared immediately
      whenever possible, or complementary testing of the preservative method to be
      used. Larger organisms are routinely eviscerated, or specific tissues are
      dissected, and analysed for stable isotopes to reduce errors introduced via the
      gut contents. Yet zooplankton gut clearance is rarely performed: the gut content
      assumed to be negligible relative to organism mass. Experimental determinations
      of relative gut mass, from both original and compiled data, range from 1-26% for
      different zooplankton species. Using reported isotopic values of basal resources
      from natural systems, we calculated that, when analysing bulk zooplankton,
      inclusion of the gut mass may introduce substantial errors of >3 per thousand.
      Thus it appears prudent to perform the simple procedure of gut clearance,
      especially for copepod species.

PMID- 14648897
TI  - Use of compound-specific delta13C and deltaD stable isotope measurements as an
      aid in the source apportionment of polyaromatic hydrocarbons.
AB  - The potential of using compound-specific stable carbon isotopic analysis for the
      source apportionment of environmental polycyclic aromatic hydrocarbons (PAHs) has
      already been demonstrated by the authors, and other researchers. PAHs arising
      from wood burning and vehicle emissions have been shown to exhibit different
      isotopic signatures, and the isotopic compositions of n-alkanes and PAHs produced
      from combustion of C3 and C4 plant species have been reported. 13C/12C isotopic
      ratios for PAHs derived from coal and wood pyrolysis and from diesel particulates
      have been noted to vary over a range by ca. 8 per thousand, which may provide a
      basis for source apportionment. In order to further improve the ability of stable
      isotope measurements to source apportion environmental PAHs, hydrogen stable
      isotopes (deltaD) of PAHs from a number of processes have been measured. The wide
      range of deltaD values, in conjunction with the delta13C values obtained, provide
      a much greater degree of differentiation between petrol and jet fuel derived
      PAHs, and between PAHs from different coal conversion processes, than the
      delta13C values alone.

PMID- 14648898
TI  - Discrimination against 13C during degradation of simple and complex substrates by
      two white rot fungi.
AB  - Changes in isotopic 13C signatures of CO2-C evolved during decomposition of a
      sugar (glucose), a fatty acid (palmitic acid), a protein (albumin), a structural
      biopolymer (lignin) and bulk plant tissue (aerial shoots from Lolium perenne)
      were monitored over a period of 76 days. All materials were sterilized and
      inoculated with either of two different species of white rot fungi, Phanerochaete
      chrysosporium or Coriolus versicolor, and incubated in sealed bottles at 28
      degrees C. The CO2 concentration in the jars was periodically determined using an
      infrared gas analyzer and its isotopic (13C) signature was assessed using a trace
      gas (ANCA TGII) module coupled to an isotope ratio mass spectrometer (IRMS,
      Europa 20-20). L. perenne material inoculated with C. versicolor showed the
      highest C mineralization activity with approximately 70% of total C evolved as
      CO2 after 76 days of incubation, followed by glucose. Substrates inoculated with
      C. versicolor generally decomposed faster than when degraded by P. chrysosporium,
      except for lignin, where no significant differences between the two fungi types
      were found and CO2-C released was less than 2% of the initial C. Considerable 13C
      isotopic fractionation during the degradation of plant tissue and of pure
      biochemical compounds was revealed as well as progressive shifts in cumulative
      CO2-13C isotopic signatures over time. During the first stages of decomposition,
      the CO2-C released was usually depleted in 13C as compared with the initial solid
      substrate, but with ongoing decomposition the CO2-C evolved became progressively
      more enriched in 13C. P. chrysosporium usually showed a slightly higher 13C
      fractionation than C. versicolor during the first decomposition phase. At
      posterior decomposition stages isotopic discrimination was often stronger by C.
      versicolor. These findings on isotopic 13C discrimination during microbial
      degradation both of simple biochemical compounds and of complex vegetal tissue
      confirmed not only the existence of significant 13C isotopic fractionation during
      plant residue decomposition, but also the existence of non-random isotopic
      distribution within substrates. They also demonstrated the ability of
      microorganisms to selectively discriminate against 13C even when degrading an
      isolated simple substrate.

PMID- 14648899
TI  - High accuracy method for the application of isotope dilution to gas
      chromatography/mass spectrometric analysis of gases.
AB  - A new isotope dilution mass spectrometry (IDMS) method for high-accuracy
      quantitative analysis of gases has been developed and validated by the analysis
      of standard mixtures of carbon dioxide in nitrogen. The method does not require
      certified isotopic reference materials and does not require direct measurements
      of the highly enriched spike. The relative uncertainty of the method is shown to
      be 0.2%. Reproduced with the permission of Her Majesty's Stationery Office.

PMID- 14648900
TI  - Measurement of the 13C/12C ratio of soil-plant individual sugars by gas
      chromatography/combustion/isotope-ratio mass spectrometry of silylated
      derivatives.
AB  - Carbohydrate is an important pool in the terrestrial carbon cycle. The potential
      offered by natural and artificial 13C-labelling techniques should therefore be
      applied to the investigation of the dynamics of individual sugars in soils. For
      this reason, we evaluated the method of 13C sugar analysis by gas
      chromatography/combustion/isotope-ratio mass spectrometry (GC/C/IRMS) after
      hydrolysis and direct trimethylsilylation. Trimethylsilylation involved the
      addition of several carbon atoms per sugar. These atoms have to be taken into
      account in the estimation of the carbon isotope ratio. The analysis of standard
      and natural pentoses and hexoses of known 13C enrichments revealed that the
      number of analysed added carbon atoms was less than expected from stoichiometry.
      This was attributed to incomplete derivatization and/or incomplete oxidation of
      methylsilyl carbon before IRMS. Using a calibration of the number of analysed
      added carbon atoms, the isotope excess of enriched samples could be determined
      with a relative error close to 5%. Concerning the determination of natural
      abundances by GC/C/IRMS, we could measure the delta 13C of standard C3- and C4
      derived sugars with an accuracy of +/-1.5 per thousand using the previous
      calibration. We were able to apply this technique to plant-soil systems labelled
      by pulse-chase of 13CO2, revealing the nature and dynamics of sugars in the plant
      rhizosphere.

PMID- 14648901
TI  - Use of liquid chromatography/time-of-flight mass spectrometry and multivariate
      statistical analysis shows promise for the detection of drug metabolites in
      biological fluids.
AB  - The process of metabolite identification is essential to the drug discovery and
      development process; this is usually achieved by liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) or a combination of liquid chromatography/mass
      spectrometry (LC/MS) and nuclear magnetic resonance (NMR) spectroscopy.
      Metabolite identification is, however, a time-consuming process requiring an
      experienced skilled scientist. Multivariate statistical analysis has been used in
      the field of metabonomics to elucidate differences in endogenous biological
      profiling due to a toxic effect or a disease state. In this paper we show how a
      combination of liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS)
      and multivariate statistical analysis can be used to detect drug metabolites in a
      biological fluid with no prior knowledge of the compound administered.

PMID- 14648902
TI  - High-throughput screening of pKa values of pharmaceuticals by pressure-assisted
      capillary electrophoresis and mass spectrometry.
AB  - A high-throughput pKa screening method based on pressure-assisted capillary
      electrophoresis (CE) and mass spectrometry (MS) is presented. Effects of buffer
      type and ionic strength on sensitivity and pKa values were investigated.
      Influence of dimethyl sulfoxide (DMSO) concentration present in the sample on
      effective mobility measurement was examined. A series of ten volatile buffers,
      covering a pH range from 2.5 to 10.5 with the same ionic strength, was employed.
      The application of volatile background electrolytes resulted in significant
      signal increase as compared with commonly used non-volatile phosphate buffers. In
      general, the CE/MS system provided a ten-fold higher sensitivity than
      conventional UV detection. The newly developed CE/MS method offers high
      throughput capacity by pooling a number of compounds into a single sample.
      Simultaneous measurement of more than 50 compounds was readily achieved in less
      than 150 min. The measured pKa values are consistent with the published data
      obtained from the CE/UV method and are also in good agreement with data generated
      by other methods. Other advantages of using CE/MS for pKa screening are
      illustrated with typical examples, including poorly soluble compounds and non-UV
      absorbing compounds.

PMID- 14648903
TI  - Matrix-assisted laser desorption/ionisation mass spectrometry in the study of
      polycondensation of Ti(OBun)4 in the presence of Si(OEt)4.
AB  - The hydrolysis-polycondensation behaviour of alcoholic solutions containing
      Si(OEt)4 and Ti(OBun)4, in different molar ratios (Si/Ti = 10-0.2), was analysed
      by laser desorption/ionisation (LDI) and matrix-assisted laser
      desorption/ionisation (MALDI) mass spectrometry. The solutions were prepared
      using operating conditions usually employed in the sol-gel synthesis of SiO2-TiO2
      materials. In accord with the well-known procedures for controlling the different
      chemical reactivities of the alkoxides, the pre-hydrolysis of the slower reacting
      silicon ethoxide and the chelation by acetylacetone of the faster reacting
      titanium butoxide were performed before mass spectrometric analysis. While LDI-MS
      did not provide evidence for the presence of mixed Si-Ti species in samples
      obtained from these reactions, MALDI-MS of samples diluted with chloroform and
      using 2,5-dihydroxybenzoic acid (DHB) as matrix led to detection of various
      oligomers with different contents of Si and Ti atoms. The results suggest that
      the formation of Si-Ti mixed oligomers seems to be the favoured process,
      especially for solutions in which one of the two components is diluted.

PMID- 14648904
TI  - Analysis of ketones by selected ion flow tube mass spectrometry.
AB  - A selected ion flow tube mass spectrometry (SIFT-MS) study of the reactions of
      H3O+, NO+ and O2+* ions with the ketones (M) 2-heptanone, 2-octanone, 2-nonanone,
      2-undecanone and 2-aminoacetophenone has been conducted in preparation for
      studies of volatile emissions from bacteria. The H3O+ reactions all proceed
      rapidly via exothermic proton transfer, producing only MH+ ions that form their
      monohydrates when water vapour is present in the helium carrier gas. The O2+*
      reactions proceed rapidly via dissociative charge transfer producing parent
      cations M+* and some fragment ions. The NO+ reactions form the NO+M adduct ions
      at rates which are dependent on the pressure of the helium carrier gas. Combining
      the present NO+ kinetic data with those available from previous SIFT studies, the
      phenomenon of charge transfer complexing is clearly demonstrated. This results in
      adduct formation in these NO+/ketone reactions at or near the collisional rate.
      SIFT-MS spectra are presented to illustrate the simplicity of SIFT-MS analysis of
      ketones using both H3O+ and NO+ precursor ions.

PMID- 14648905
TI  - Simultaneous measurement of drug metabolic stability and identification of
      metabolites using ion-trap mass spectrometry.
AB  - The use of in vitro drug metabolism data in the understanding of in vivo
      pharmacokinetic, safety and toxicity data has become a large area of scientific
      interest. This has stemmed from a trend in the pharmaceutical industry to use in
      vitro data generated from human tissue as a criterion to select compounds for
      further investigation. As well as measuring metabolic stability in vitro using
      human liver microsomal preparations, the identification of possible metabolite(s)
      formed may play a vital role in Hit-to-Lead and Lead optimisation processes. The
      data-dependent scan function mode with the ion-trap instrumentation provides the
      ability to measure the metabolic stability and identification of possible
      metabolites of a compound. A gradient liquid chromatographic method with a run
      time of 6 min/injection was developed for this purpose. The approach of
      simultaneous metabolic stability measurements and rapid identification of
      metabolites of drugs with high (verapamil), medium (propranolol and cisapride)
      and low (flunarazine) metabolic stabilities using ion-trap mass spectrometry is
      described. The metabolites identified after 15 min incubation for verapamil,
      propranolol and cisapride are in good agreement with those reported as the major
      metabolites in human in vivo studies.

PMID- 14648906
TI  - Practical considerations in the gas chromatography/combustion/isotope ratio
      monitoring mass spectrometry of 13C-enriched compounds: detection limits and
      carryover effects.
AB  - This paper describes a methodological investigation of the use of gas
      chromatography/combustion/isotope ratio monitoring mass spectrometry (GC/C/IRMS)
      for the compound-specific stable isotope analysis of 13C-enriched compounds.
      Analysis of two 13C-enriched fatty acid methyl esters, possessing delta13C values
      of approximately 500 per thousand, at a range of concentrations, demonstrated
      that detectable responses, i.e. chromatographic peaks, could be observed in the
      45/44 output even when the compound was present in such low abundance that no
      peak was observed in the m/z 44 ion chromatogram. A limit of detection, defined
      as the point at which the signal-to-background ratio was equal to 3, was
      calculated for two compounds and for both ion chromatograms. The limit of
      detection in the 45/44 chromatogram was found to be ca. 30 pg injected for methyl
      13C-hexadecanoate and ca. 20 pg injected for methyl 13C-octadecanoate, whilst, in
      the m/z 44 ion chromatogram, detection limits were approximately 180 and
      approximately 200 pg, respectively. The delta13C value recorded for the analytes
      was found to be both inaccurate and imprecise below 5 ng of each component
      injected, although this would not represent a significant drawback in qualitative
      tracer-type experiments. In a further study of co-injected mixtures of labelled
      (approximately 500 per thousand) and unlabelled (natural abundance, -20 to -30
      per thousand ) fatty acid methyl esters a significant within-run carryover effect
      was observed, where the isotope values recorded for compounds eluting immediately
      after enriched components were significantly affected. Whilst this would not
      affect qualitative results, quantitative data for mixtures containing enriched
      compounds should be considered with caution. The standards employed in this
      investigation were enriched to approximately 500 per thousand in 13C; however,
      these effects would probably be accentuated at higher levels of labelling and
      with other elements. The limit of detection work demonstrated the potential of
      GC/C/IRMS as a highly sensitive and selective detector with many possible
      applications.

PMID- 14648908
TI  - Laser desorption/ionization mass spectrometry on sol-gel-derived dihydroxybenzoic
      acid isomeric films.

PMID- 14648907
TI  - Automated analysis of 13C/12C ratios in CO2 and dissolved inorganic carbon for
      ecological and environmental applications.
AB  - Stable carbon isotope ratios (13C/12C) are a valuable tool for studying a wide
      range of environmental processes, including carbon cycling and subsurface
      microbial activity. Recent advances in automated analysis provide the opportunity
      to increase greatly the ease and consistency of isotopic analysis. This study
      evaluated an automated headspace sampler linked to a commercially available CO2
      preconcentration system and continuous flow isotope ratio mass spectrometer.
      Field sampling and analysis methods are illustrated for delta13C of soil respired
      CO2, from both tracer and natural abundance experiments, and dissolved inorganic
      carbon from contaminated groundwater. The automated system demonstrated accuracy,
      precision, and linearity, with standard errors below 0.1 per thousand for
      replicate gas standards run at concentrations varying five-fold. It measured 40
      samples per 10-hour run, with concentrations ranging from ppb to percentage
      levels. In the field, gas samples were injected into nitrogen-filled autosampler
      vials, thereby allowing use of small sample volumes, control of analyte
      concentration, and direct analysis by the automated system with no further
      preparation. A significant linear relationship between standard concentrations
      and peak area allows for accurate estimates of sample CO2 concentration from the
      mass spectrometric data. The ability to analyze multiple small-volume samples
      with minimal off-line preparation should enhance the application of isotopes to
      well-replicated field experiments for process-level studies and spatial and
      temporal scaling.

PMID- 14648909
TI  - Rapid diagnosis of medium chain Acyl Co-A dehydrogenase (MCAD) deficiency in a
      newborn by liquid chromatography/tandem mass spectrometry.

PMID- 14648910
TI  - Management of HIV patients.

PMID- 14648911
TI  - HIV and AIDS--the ethical dilemma central to many issues in HIV/AIDS revolves
      around individual good versus societal good.
AB  - Using patient advocacy as a point of departure, there are three possible ethical
      options where the human immunodeficiency virus/acquired immune deficiency
      syndrome (HIV/AIDS) is concerned: a 'strict advocacy' approach, a 'moderate
      advocacy' approach and a 'no advocacy' approach. In South Africa, a 'moderate
      advocacy' approach is favoured in general.

PMID- 14648912
TI  - The evolution of moral thinking.

PMID- 14648913
TI  - Respect for patient autonomy.
AB  - Respect for patient autonomy creates the following obligations: informed consent,
      confidentiality, truth-telling and effective communication. Patient autonomy is
      becoming increasingly important in postmodern medicine and is changing the nature
      of the doctor--patient relationship.

PMID- 14648914
TI  - The maxillae: integrated and applied anatomy relevant to dentistry.
AB  - The union of the two paired maxillae form the whole upper jaw. Individual
      components of the maxilla contribute to the formation of the face, nose, mouth
      and orbit. The bony surfaces are in relation to the infratemporal and
      pterygopalatine fossae. Grooves, openings and foramina lend passage to structures
      such as the infra-orbital, posterior superior alveolar, nasopalatine and greater
      palatine nerves. These nerves are of great importance for regional anaesthesia in
      dentistry. The maxillary antrum of Highmore is frequently affected by
      pathological processes such as accidental tooth root impaction during an
      extraction procedure, sinusitis, cysts, fractures (LeFort) and tumours. Fast
      growing maxillary sinus tumours often breach the thin walls of this cavity and
      encroach upon adjacent structures such as the orbit, nose, cheek, infratemporal
      fossa and mouth. 'Blow-out' fractures through the orbital component may result in
      nerve and muscle entrapment. Alveolar processes form an arcade for the two
      incisors, one canine, two premolars and three molars on each side. Knowledge of
      regional and applied anatomy, relevant to the maxillae, is essential when
      considering diagnostic imaging by X-rays, CT, and MRI.

PMID- 14648915
TI  - Use of lead aprons.

PMID- 14648916
TI  - Relevance of the pharyngotympanic tube.
AB  - The auditory (Eustachian) tube connects the middle ear with the nasopharynx. This
      conduit permits equalisation of pressure between the middle ear and the throat.
      Balanced pressure allows the eardrum to vibrate freely as sound waves strike it.
      The auditory tube is also a potential anatomical route whereby opportunistic
      pathogens may migrate from the nose and throat to the middle ear. Eustachian tube
      (ET) function is disturbed in children with cleft palate, thereby rendering them
      susceptible to chronic otitis media with effusion (OME) and temporary conductive
      deafness. ET obstruction follows in these patients, and is thought to be related
      to the inability of the tensor veli palatini (TVP) to function properly. This
      anatomical overview reviews the clinical importance of the ET in the normal
      population and children with cleft palate.

PMID- 14648917
TI  - Cleidocranial dysplasia--a case revisited.

PMID- 14648918
TI  - General practitioner's radiology case 15. Ectodermal dysplasia.

PMID- 14648919
TI  - "Advances in thrombosis and haemostasis".

PMID- 14648920
TI  - Congestive heart failure and Virchow's triad: a neglected association.
AB  - Congestive heart failure (CHF) is associated with significant morbidity and
      mortality. In particular, patients with CHF have a high risk of venous
      thromboembolism and stroke, as well as recurrent ischaemia and infarction.
      However, in large heart failure trials, such thrombotic complications have often
      been regarded as less important end points than total mortality or readmission to
      hospital. In addition, a high proportion of mortality in CHF is due to sudden
      cardiac death (SCD). Although it was long thought that SCD was due to malignant
      arrhythmias, current evidence suggests that thrombosis also has a significant
      part to play. Thrombosis in CHF may therefore be a much more significant problem
      than is generally appreciated. CHF is associated with abnormalities of flow (low
      cardiac output, dilated cardiac chambers), vessel wall (endothelial dysfunction),
      and abnormalities of blood constituents (abnormalities of platelets and
      haemorrheology). Thus it fulfills all of Virchow's triad of characteristics of a
      prothrombotic state. In view of these findings, antithrombotic therapy ought to
      provide a substantial morbidity and mortality benefit to patients with CHF.
      However, current data is conflicting, and comes from non-randomised,
      retrospective analyses of major heart failure trials, and a few randomised trials
      of anticoagulants in CHF that are more than 50 years old. Prospective trials of
      warfarin and antiplatelet agents in CHF are in progress. Measures to identify
      patients at highest risk of thrombosis may help to guide treatment. Further study
      into the relationships between such markers and the severity of heart failure,
      the value of such markers in predicting thrombotic complications in CHF, and the
      effect of treatments, is therefore needed.

PMID- 14648921
TI  - Is there an increased frequency of autoimmune thrombocytopenia in hepatitis C
      infection? A review.
AB  - Thrombocytopenia is common in chronic liver disorders, and may be due to a
      variety of non-immune and immune mechanisms. The latter include clearance of
      immune complexes, or increased platelet sequestration driven from an antigen
      antibody immune response. A number of case observations led to the assumption
      that autoimmune thrombocytopenia (AITP) is a common feature in HCV infected
      individuals, while it is rare in non-immune chronic liver disease. Clinically,
      the differentiation of AITP from other forms of thrombocytopenia can influence
      therapeutic measures. Therefore, in HCV infection it is mandatory to disclose the
      pathomechanisms of thrombocytopenia in each case individually. In this article we
      will discuss the various pathomechanisms that may result in thrombocytopenia in
      HCV infection, review the current literature with reference to an increased
      occurrence of AITP in HCV infected patients, and how laboratory tools may assist
      in the diagnosis. Finally, we will address some of the questions that need to be
      answered to get a clearer impression of laboratory and clinical parameters
      pertaining to a possible association of AITP in HCV.

PMID- 14648922
TI  - Prevention and treatment of bleeding by pro-hemostatic treatment strategies.
AB  - Pro-hemostatic therapy may achieve an improvement of hemostasis, by amelioration
      of primary hemostasis, stimulation of fibrin formation or inhibition of
      fibrinolysis. Pro-hemostatic interventions appear to be effective in reducing
      peri-operative blood loss and reducing transfusion requirements in specific
      situations and may be helpful adjuncts in the management of severe spontaneous
      and post-operative bleeding. The risk of a higher incidence of thrombotic
      complications associated with the use of pro-hemostatic therapy is unknown but
      seems not to be very high in clinical practice. There is a need for more
      systematic and adequately controlled clinical observations to better establish
      the efficacy and safety of pro-hemostatic interventions.

PMID- 14648923
TI  - Novel anticoagulants for the prevention and treatment of venous thromboembolism.
AB  - Unfractionated heparin, low molecular weight heparin and vitamin K antagonists
      are anticoagulants currently used for the prevention and treatment of deep vein
      thrombosis and pulmonary embolism. Considerable limitations of these agents, such
      as a narrow therapeutic window, a variable dose response or lack of oral
      bioavailability, created the need for new anticoagulants. Numerous new compounds
      with different mechanisms of action have been developed and some have been
      already approved for clinical use. Quite recently, fondaparinux, an indirect anti
      factor Xa inhibitor, has been licensed in Europe and in the US for prevention of
      VTE in patients undergoing hip or knee replacement surgery. In addition,
      lepirudin, a recombinant hirudin derivative, and the heparinoid danaparoid, have
      been approved in Austria for treatment of heparin-induced thrombocytopenia.
      Recombinant nematode anticoagulant protein c2, the orally available thrombin
      inhibitor ximelagatran and ART-123, a recombinant soluble thrombomodulin, are in
      advanced stages of clinical development. This article reviews mechanisms and
      sites of action, and the current state of preclinical and clinical research of
      these and various other agents with respect to the prevention and treatment of
      venous thromboembolism).

PMID- 14648924
TI  - Hypertrophy of inferior turbinates: radiofrequency surgery.
AB  - Hypertrophy of the inferior turbinates can be treated by surgical reduction that
      seems to the most effective approach. Currently, several surgical techniques are
      performed, like turbinectomy, galvanic or laser cauterization, surgical
      submucosal decongestion and cryosurgery. In this study, we describe a procedure
      to reduce the hypertrophy of the inferior turbinates in 60 patients by radio
      frequency with electrosurgical equipment. The aim of this study is to show how to
      carry out this technique in the outpatient practice, that allows to face this
      pathology in an effective and rapid way.

PMID- 14648925
TI  - A novel method for diagnosing chronic rhinosinusitis based on an electronic nose.
AB  - The nasal out-breath of persons with chronic nasal and/or paranasal infections
      may have characteristic strange odors, which in our experience are in most cases
      related to bacterial and/or fungal infections of the sinuses. The objective of
      the present study was to examine nasal out-breath samples from patients with
      chronic rhinosinusitis (CRS) (with or without polyposis) and healthy control
      volunteers using the electronic-nose (EN) technology. We developed a simple
      technique for collecting samples of nasal out-breath in disposable sterile
      plastic sacks with a tight closing seal. The principal component analysis
      correctly classified all individual EN patterns for CRS patients and
      misclassified 2 samples from the healthy controls (80.0% successful
      classification rate). The artificial neural network analysis correctly classified
      60.0% of the patterns of both groups. We believe that the use of methodologies
      based on EN technology, combined with conventional clinical examinations, may
      improve the diagnosis of chronic rhinosinusitis.

PMID- 14648926
TI  - [Hyperparathyroidism associated with thyroid disease. Retrospective study of 15
      patients treated in 11 years].
AB  - The association of hyperparathyroidism with thyroid pathology previous to surgery
      is not very frequent in our cases, almost a 15%, but it means another difficulty
      for the diagnostic and treatment. Between 1991 and 2001 we have studied and
      operated 15 patients with this clinic association. 14 were female and only 1 male
      with a range age of 59 years old. We studied the type of hyperparathyroidism,
      personal history, clinic, type of thyroid pathology associated, complementary
      explorations, type of surgery, anatomopathology evolution, and hospital stay. We
      have done 12 adenoma resections, 1 subtotal parathyroidectomy, 2 total
      thyroidectomies and 5 hemithyroidectomies. Only in one patient the
      anatomopathology was informed as a thyroid carcinoma associated to a parathyroid
      adenoma, being the other patients benign pathologies. We did literaturer revision
      on this association. We believe that in all patients with a thyroid pathology we
      should an associated hyperparathyroidism and vice versa.

PMID- 14648927
TI  - Cyfra 21.1, TPS and SCC in squamous cell carcinoma of larynx.
AB  - BACKGROUND: Serologic tumor markers are actually a valuable tool for diagnosis,
      management and follow up in some cancer types. The concentrations of Cyfra 21.1,
      SCC and TPS has been analysed in several groups of head and neck tumors, but
      exclusively in larynx there are no studies concerning this subject. AIMS: The
      purpose of the present study was to assess the expression of serum fragments of
      cytokeratins (CK's) 18/19, and squamous cell carcinoma antigen (SCCA) in a same
      group of patients with squamous cell carcinoma of larynx, and correlate the
      results with tumor localisation, T, stage, histology, presence of regional
      metastasis, and smoking habits. METHODS: Forty six patients treated at the
      Department of Otorhinolaryngology, Porto Center of the Portuguese Institute of
      Oncology were enrolled in the study. Blood samples were obtained before
      treatment, and determinations effectuated using standard commercial available
      kits. RESULTS: Although serum concentrations of Cyfra 21.1, TPS and SCC were not
      significantly elevated in patients with laryngeal cancer, more expressive levels
      namely for TPS were observed in advanced supraglotic and metastasis tumors
      independent of the differentiation degree.

PMID- 14648928
TI  - [Treatment of thyroid cancer. Retrospective study and review of the literature].
AB  - We present a retrospective study about our experience in the treatment of thyroid
      carcinoma. For that, between 1992 and 1997, we have collected 37 malignant
      thyroid tumours (15%) over 250 operations on thyroid gland by our ENT Service. We
      analysed several variables: Age, sex, personal antecedents, clinical symptoms,
      results of the complementary tests (thyroid hormones, ultrasonography,
      scintigraphy and FNAB), type of surgery complications and number of recurrences.
      The thyroid carcinomas, specially differentiated tumors, are an increasing
      pathology with tendency to affect females. In our serie usually they are solitary
      thyroid nodes, scintigraphically cold ones, in which FNAB as the best test. We
      think that a total thyroidectomy is the best treatment and it must be made by an
      ENT.

PMID- 14648929
TI  - [Metastatic neck adenopathies without known primary tumor. Incidence study 1996
      2001].
AB  - We made a retrospective descriptive study reviewing 92 patients with cervical
      lymph node metastases from  unknown primary tumour. The study was accomplished
      during 6 years. (January 1996 to December 2001) in the Department of
      Otorhinolaryngology of the Hospital Reina Sofia, Cordoba. The median age was 61.7
      years old, male 96.7% and heavy smoker (89.1%) and drinkers most of them.
      According to TNM categories, 72.2% patients were in phase N2a and half of them
      were localized Level II. Squamous cell carcinoma was the predominant histologic
      type. The patients were treated with surgery in 70.6% of the cases with or
      without radiation therapy and/or chemotherapy.

PMID- 14648930
TI  - [Extramedullary plasmacytoma of the head and neck. Report of 3 clinical cases].
AB  - Plasmocytomas are neoplasic disorders arising from plasma cells that include
      Multiple Myeloma (MM) Solitary Plasmocytoma of the bone and Extramedullary
      Plasmacytoma (EMP). EMP are solitary tumours consisting of plasma cell
      proliferation that occurs in locations other than bone. A variable percentage may
      be associated at a later date with the development of MM. EMP represent up to 4%
      of nonepithelial tumours of the upper respiratory tract. They generally occur in
      the submucosal tissue of the upper airways (80% of cases), with a predilection
      for nasopharynx, nasal cavity, paranasal sinuses and tonsils. We report 3 cases
      of Extramedullary Plasmocytoma located one in the upper respiratory tract. All
      the patients underwent surgical resection or biopsy of the lesion that allowed
      the histological study, which showed a plasma cell proliferation. Serum and bone
      marrow studies conclude the diagnosis of Extramedullary Plasmocytoma. The
      treatment was radiotherapy, with or without previously surgery. Three patients
      are currently under close follow-up and no evidence of recurrence has been found.
      We review the clinic, diagnostic, therapeutic and prognostic aspects of this kind
      of tumours.

PMID- 14648931
TI  - [Our experience with extranodal lymphomas of the ORL region].
AB  - Head and neck extranodal lymphomas are rare. Waldeyer lymphatic ring is the most
      common localisation of these lymphomas, followed by oral cavity and parothoid
      glands. We have done a retrospective study of patients with extranodal lymphomas
      diagnosed in our hospital between 1991 and 1999. We have included in this study
      23 patients, 15 males and 9 females. We have used the REAL classification. All of
      them have been non-Hodgkin lymphomas. The rhinopharynx has been the most affected
      region, followed by the palatine tonsils and oral cavity. Most of them were of
      medium degree and they were in the initial stages. The presentation symptoms
      varied depending on the localisation. The age, stage and histologic degree were
      important for the treatment election.

PMID- 14648932
TI  - [Forestier-Rotes Querol syndrome].
AB  - The diffuse idiopathic skeletal hyperostosis (DISH) or Forestier's disease is
      characterized by an hyperostosis of the anterolateral margin of the vertebral
      bodies. It is an uncommon cause of dysphagia in old patients. In the differential
      diagnosis of mechanical dysphagia we must have present this disease. Cervico
      dorsal spine radiographies reveal large anterior osteophytes creating pharyngeal
      encroachment.

PMID- 14648934
TI  - [Living in aging].

PMID- 14648935
TI  - [History of rehabilitation and education].

PMID- 14648936
TI  - [Quality of life project in a specialized unit, why Alzheimer's disease? For
      whom? Why?].

PMID- 14648937
TI  - [Social rehabilitation, to prevent social isolation in aging].

PMID- 14648938
TI  - [Residents on the boards].

PMID- 14648939
TI  - [Discussing and writing in institutions].

PMID- 14648940
TI  - [Press review and social ties].

PMID- 14648941
TI  - [Helping aged persons who are abused in institutions].

PMID- 14648942
TI  - [Ethics and palliative care: who, when, why?].

PMID- 14648943
TI  - [Clinical trials in oncology and elderly patients].

PMID- 14648944
TI  - [Dyspnea in the elderly subject].

PMID- 14648945
TI  - [Ergonomics and posture in geriatrics, a lasting prevention].

PMID- 14648946
TI  - Carpal tunnel syndrome in children.
AB  - Carpal tunnel syndrome (CTS) is rarely seen in children. A literature search in
      1989 revealed 52 published cases. The authors review 163 additional cases that
      were published since that date. The majority of these cases were related with a
      genetic condition. The most common aetiology was lysosomal storage disease:
      mucopolysaccharidoses (MPS) in 95 and mucolipidoses (ML) in 22. In CTS secondary
      to MPS, clinical signs typical of adult CTS are rarely seen, and difficulty with
      fine motor tasks is the most frequent finding. CTS in MPS does not seem to be
      prevented by bone marrow transplantation, the usual treatment for the condition.
      CTS is probably due to a combination of excessive lysosomal storage in the
      connective tissue of the flexor retinaculum and a distorted anatomy because of
      underlying bone dysplasia. Mucolipidoses come next in the aetiology, with
      essentially similar symptoms. The authors found in the literature 11 cases of
      primary familial CTS, a condition which presents as an inheritable disorder of
      connective tissue mediated by an autosomal dominant gene; the symptoms may be
      more typical in some cases, but are more similar to MPS in others. A case with
      self-mutilation has been reported. Hereditary neuropathy with liability to
      pressure palsies (HNPP) is a rare autosomal dominant condition characterised by
      episodes of decreased sensation or palsies after slight traction or pressure on
      peripheral nerves; it may also give symptoms of CTS. Schwartz-Jampel syndrome
      (SJS), another genetic disorder with autosomal recessive skeletal dysplasia, is
      characterised by varying degrees of myotonia and chondrodysplasia; it has also
      been noted associated with CTS in a child. Melorrheostosis and Leri's syndrome
      have also been noted in children with CTS, as well as Dejerine-Sottas syndrome
      and Weill-Marchesani syndrome. Among non-genetic causes of CTS in children,
      idiopathic cases with children onset have been reported, usually but not always
      related with thickening of the transverse carpal ligament. Intensive sports
      practice has been reported as an aetiological factor in several cases of
      childhood CTS. Nerve territory oriented macrodactily, a benign localised form of
      gigantism, is another unusual cause of CTS in children, as are fibrolipomas of
      the median nerve or intraneural perineuroma or haemangioma of the median nerve.
      Acute cases have been reported in children with haemophilia, secondary to local
      bleeding. Another local cause is a musculotendinous malformation of the palmaris
      longus, the flexor digitorum superficialis, the flexor carpi radialis brevis (a
      supernumerary muscle), the first lumbricalis or the palmaris brevis. Isolated
      cases of childhood CTS have also been reported in Klippel-Trenaunay syndrome, in
      Poland's syndrome and in scleroderma. Finally, several cases have been noted
      following trauma, most often related with epiphysiolysis of the distal radius.
      Immediate reduction has cleared the problem in most cases, but exploration of the
      median nerve should be considered otherwise, and also in cases with delayed
      occurrence of symptoms. Overall 145 of the 163 reviewed cases have undergone open
      carpal tunnel release. Childhood CTS often has an unusual presentation, with
      modest complaints and children are often too young to communicate their problem.
      In CTS with specific aetiologies such as storage disease, the symptoms may be
      masked by the skeletal dysplasia and joint stiffness. Every child with even mild
      symptoms must be thoroughly examined and a family history must be taken. Children
      with storage disease may benefit from early clinical and electrophysiological
      screening before they develop obvious clinical signs.

PMID- 14648947
TI  - Polymerase chain reaction for the detection of Mycobacterium tuberculosis in
      synovial fluid, tissue samples, bone marrow aspirate and peripheral blood.
AB  - Extrapulmonary tuberculosis accounts for approximately 10% of tuberculous
      infections; the musculoskeletal system is involved in a small number of these
      (10%). Skeletal tuberculosis is an indolent disease, and diagnosis may be
      delayed. Conventional methods are time consuming and have a low sensitivity rate.
      In recent years PCR-based protocols raised hopes as a reliable and fast
      diagnostic tool for extrapulmonary tuberculosis. The authors report the detection
      of Mycobacterium tuberculosis complex DNA in specimens from six patients using a
      nested PCR protocol specific for IS6110 insertion element of Mycobacterium
      tuberculosis complex. Three men and three women are reported with ages ranging
      from 42 to 68 years. The sites of infection were the knee and shoulder in one
      case each, the hip in two cases, and the thoracic spine in two cases. Diagnosis
      was established within three days, and treatment was initiated promptly. PCR is a
      technically easy approach that can be used as a first step diagnostic tool for
      early recognition and treatment of bone and joint tuberculosis.

PMID- 14648948
TI  - Risks and complications of prolonged parenteral antibiotic treatment in children
      with acute osteoarticular infections.
AB  - This study aimed at assessing the prevalence of complications encountered during
      prolonged intravenous antibiotic (AB) therapy when treating acute osteoarticular
      (OA) infections in children. We reviewed retrospectively 60 paediatric patients
      treated in our department between 1988 and 1998 for acute osteoarticular
      infections (27 with acute haematogenous osteomyelitis, 25 with septic arthritis
      and 8 with septic osteoarthritis). C-reactive protein, erythrocyte sedimentation
      rate (ESR), and full blood count were monitored during the entire treatment. Body
      temperature was recorded three times per day until the fever subsided, and then
      daily during the remaining hospitalisation. Finally, we listed complications
      related to the antibiotic therapy and those linked to the presence of a venous
      catheter. Seventeen allergic reactions to drugs were recorded during the
      intravenous AB therapy. This complications occurred on average after 24.4 +/- 4.4
      days of treatment. The clinical manifestations most often encountered were a
      delayed rise in temperature and cutaneous symptoms. Blood tests showed an
      isolated increase in the ESR and eosinophilia (> 1000 eosinophils/ml). Four
      venous catheters had to be removed, in two cases owing to their obstruction and
      in two cases owing to an infection. Prolonged intravenous AB therapy is not
      without complications due to its duration and its mode of administration. Drug
      allergies to AB constitute a major complication of the treatment. They may render
      the treatment of subsequent infections problematic and expose these patients to
      major allergic reactions if they accidentally encounter the molecule
      incriminated. Moreover, the anaesthetics required to insert a central venous
      catheter and the need to leave it in place for a prolonged duration constitute
      another source of potential complications. The duration of i.v. AB therapy could
      therefore be shortened if the clinical and biological evolution is favourable and
      the pathogen is identified.

PMID- 14648949
TI  - The aetiology and outcome of 170 ulnar nerve lesions confirmed with
      electrophysiological testing.
AB  - The authors have studied 148 consecutive patients with 170 electrophysiologically
      confirmed ulnar nerve lesions, who were followed up for one to six years (median
      3.8 years) to determine clinical progress and outcome. Injury and intra-operative
      pressure accounted for 12.9% and 7.1% of lesions respectively; 58.2% were
      idiopathic with no identified clinical aetiological factor. Eighty-three percent
      received non-operative treatment initially; 21% of these required operative
      intervention following further clinical/electrophysiological assessment. Partial
      or complete recovery occurred in 92% of intra-operative, 64% of idiopathic and
      50% of injury cases respectively. Ulnar nerve lesions predominate in males and
      can be treated non-operatively providing clinical and electrophysiological
      monitoring is possible. Bilaterality is common and should be excluded. Lesions
      due to injury have a worse prognosis than those caused by direct continuous or
      repeated pressure, inflammation or where no aetiological factor exists.

PMID- 14648950
TI  - Radiological remodelling of the acetabulum in Perthes' disease.
AB  - Thirty-four patients were studied throughout the evolution of Perthes' disease.
      The acetabular changes included osteopoenia of the roof, irregularity of its
      contour, and decrease in its depth. These changes were proportional to the
      femoral head involvement. The purpose of the study was to assess the effect of
      the morphological changes of the femoral head on the acetabulum and the outcome,
      and to determine the extent to which coxa magna and acetabular enlargement
      induced by Perthes disease in childhood persist into adolescence. Radioisotope
      scans of the hip were examined in fourteen children with unilateral Perthes'
      disease and comparison was made with the contralateral hip. These scans showed
      increased uptake on the lateral part of the acetabulum and no uptake over the
      avascular part of the femoral head. Average follow-up was ten years and children
      were followed up on average from six years to fifteen years of age. Six readings
      of the measurements of various dimensions of the acetabulum and the femoral head
      were done. CT scan also showed irregularity in the acetabulum. Statistical tests
      lead to the conclusion that the decrease in the depth of the acetabulum was
      secondary to the femoral head involvement and the extent of its dimensional
      changes affected the final congruity between the femoral head and the acetabulum.
      Also the remodelling potential of the acetabulum decreases as the child grows
      older. Therefore containment procedures could be done by femoral osteotomy in
      younger children, whereas acetabular osteotomy may benefit older children.

PMID- 14648951
TI  - Changes in body mass index following primary elective total hip arthroplasty.
      Correlation with outcome at 2 years.
AB  - Weight has been shown to increase following total hip arthroplasty (THA). It is
      also reported that the preoperative weight does not correlate to the outcome of
      the surgery. Body mass index (BMI) is regarded as a better tool for analysis.
      However, only a few studies have analysed BMI, BMI change or its correlation to
      the outcome. We present a retrospective study of 78 consecutive patients
      undergoing elective primary cemented THA for osteoarthritis (OA) with a minimum 2
      year follow-up from a single centre. Only 26% had an acceptable BMI at the time
      of surgery and at follow-up, there was a mean absolute weight increase of 2.5%
      and BMI increase of 2.1%. Fifty seven percent correctly predicted their weight
      change. BMI values were independent of the level of satisfaction or mobility
      using Western Ontario McMaster Universities OA Index (WOMAC) score and SF12
      score. We conclude that the majority of patients undergoing primary THA will
      increase their BMI given sufficient follow-up irrespective of the outcome. Pre
      operative BMI or BMI change post operatively is not a predictor of complications
      or mid term outcome of THA.

PMID- 14648952
TI  - Temporary epiphysiodesis with Blount stapling for treatment of idiopathic genua
      valga in children.
AB  - Not all idiopathic genua valga in children show an innocuous evolution. If the
      deformity persists or increases, it can cause a long-term cosmetic or functional
      problem. The problem can easily be corrected, with only limited risks for
      complications, with temporary medial hemi-epiphysiodesis of the growth plates
      around the knees. This retrospective study considers the pre- and postoperative
      evolution of 44 patients who underwent temporary stapling of the medial femoral
      and tibial physes following Blount's technique. Ninety percent were satisfied and
      showed good correction of the knee alignment. Four patients were not satisfied
      with the result, owing to recurrence of the valgus deformity; two of them had a
      good result after revision surgery. The condition was assessed by measuring
      clinically the intermalleolar distance and the radiological hip-knee-ankle angle.
      Average age at the time of surgery was 12 years six months for girls and 13 years
      eight months for boys. Pre-operative evaluation of skeletal age on radiographs of
      the hand is advised. There is a rebound phenomenon after hardware removal, with
      an average recurrence of the valgus deformity of 4 degrees. Blount stapling
      appears as a reliable method for treatment of idiopathic genua valga in children,
      with satisfactory results and few complications.

PMID- 14648953
TI  - In vitro investigation of knee joint kinematics following cruciate retaining
      versus cruciate sacrificing total knee arthroplasty.
AB  - The aim of this biomechanical study was to investigate knee joint kinematics
      following total knee arthroplasty. We compared eight congruent posterior cruciate
      ligament retaining and four ultracongruent cruciate sacrificing Natural Knee
      prostheses to the untreated human cadaveric knee joint. A six-degree-of-freedom
      testing device was used to evaluate knee joint kinematics with a load of 300
      Newton and without load application (0 Newton). Statistical analysis was
      performed using the Wilcoxon rank sum test. A significant increase in antero
      posterior translation and tibial rotation was seen in both types of total knee
      arthroplasty. Implantation of the ultracongruent prosthesis was followed by
      distinctly more kinematic changes in comparison to the congruent prosthesis. Load
      application of 300 Newton leads to an anterior dislocation of the femoral
      component of the ultracongruent prosthesis at 60 degrees of flexion in vitro,
      indicating an increased demand of compensatory muscular activity in vivo.

PMID- 14648954
TI  - Spontaneous healing of large femoral cortical bone defects: does genetic
      predisposition play a role?
AB  - Traumatic segmental femoral defects are commonly high velocity injuries and their
      reconstruction necessitates challenging surgical procedures. These injuries
      present commonly as open fractures and thorough wound debridement followed by
      adequate soft tissue cover is mandatory before skeletal reconstruction can be
      commenced. The definitive reconstructive procedure is therefore often delayed and
      the optimal treatment option is frequently determined by the extent of the
      cortical defect. The complication rate is high and femoral non-union is not
      uncommon in these injuries but associated head injuries as part of a polytrauma
      can have a positive effect on fracture healing. We are presenting a series of
      four cases, in which traumatic segmental femoral defects of 6, 9, 10 and 15 cm
      without associated head injury healed spontaneously while the patients were
      waiting for a definitive skeletal reconstructive procedure.

PMID- 14648955
TI  - Percutaneous destruction and alcoholisation for the management of osteoid
      osteoma.
AB  - Osteoid osteoma (OO) is a small, self-limiting, benign osteogenic tumour.
      Successful treatment of OO requires complete resection or destruction of the
      nidus. Surgery, which consists of en bloc excision of the nidus, followed by
      internal fixation, bone grafting, or both, is successful in almost all cases. In
      a small percentage of cases the nidus may be missed at surgery, resulting in a
      failed procedure. The aim of this study was to evaluate the results of
      percutaneous destruction and alcoholisation as a treatment of OO. Fifteen
      patients with an osteoid osteoma (10 males, 5 females) were treated in the
      Oncology Unit, Orthopaedic Department, Mansoura University Hospital. Three OOs
      were localised in the humerus, 5 in the femur, 6 in the tibia and fibula, and one
      in the talus. All patients underwent destruction of the nidus by determining the
      nidus by CT, drilling with a cannulated drill bit, curretting with a speed burr
      and injecting ethanol. The nidus completely disappeared on the postoperative CT
      scan. The average follow-up period was 19 months (6-24 months). There were no
      postoperative complications. This technique for the treatment of OO is minimally
      invasive, safe, simple, and cost effective. It allows an early return to normal
      activities. The procedure is particularly useful for a lesion located deep in the
      skeleton, which would require an extensive approach with conventional surgery.

PMID- 14648956
TI  - Palmar dislocation of the lunate bone with complete disruption of all ligaments.
      A report on two cases.
AB  - Complete disruption of the lunate from both dorsal and palmar ligamentous
      attachments caused by palmar dislocation has rarely been reported. The authors
      present two cases and discuss the surgical treatments performed. They conclude
      from these cases that the lunate is at risk for remaining avascular after such
      trauma, so that proximal row carpectomy should be considered as a surgical option
      in the primary treatment.

PMID- 14648957
TI  - Symptomatic Linburg-Comstock syndrome: a case report.
AB  - The authors report the case of a 39-year-old woman with pain in the right
      dominant hand after initiating a crafts course. Clinical examination revealed
      tenderness on the volar side of the thumb and wrist. Simultaneous flexion of the
      distal interphalangeal joint of the index finger with flexion of the
      interphalangeal joint of the thumb was observed. Operative procedure confirmed
      the presumed diagnosis of an anomalous connection between the flexor pollicis
      longus and the flexor digitorum profundus tendon to the index finger, first
      described in 1979 by Linburg and Comstock.

PMID- 14648958
TI  - Bone diseases in children receiving growth hormone.
AB  - The authors report two cases of bone disorders in children with short stature,
      with confirmed growth hormone (GH) deficiency treated by GH supplementation. The
      first patient, aged 15 years, developed avascular necrosis of the femoral head
      and scoliosis. The second one, aged 17 years, had avascular necrosis of the
      femoral capital epiphysis on one side and acute slipped capital femoral epiphysis
      (SCFE) on the other side. All these complications were diagnosed while they were
      receiving GH-therapy. The exact aetiology and the role of GH in the pathogenesis
      of these conditions are still unknown.

PMID- 14648959
TI  - Head-neck disassembly of an uncemented revision stem treated by addition of a
      proximal spacer.
AB  - A 67-year-old woman underwent revision total hip replacement with a long,
      distally fixed uncemented stem inserted through a transfemoral approach. Initial
      stability was not achieved and the stem subsided early. Probably due to a
      conflict with the minor trochanter, the prosthetic head detached from its neck.
      Instead of a re-revision of the stem, a proximal spacer was inserted to restore
      stability and to compensate for leg-length discrepancy. This has proved to be a
      stable and satisfactory solution after three years follow-up.

PMID- 14648960
TI  - Chondroblastoma of the distal femur. A case report.
AB  - The authors report a case of chondroblastoma which was localised in the distal
      femoral epiphysis in a 16-year-old boy. The lesion was large, rapidly expanding
      and extended into the knee joint. After diagnostic evaluation including tru-cut
      biopsy, the lesion was treated surgically with curettage and grafting with
      coralline hydroxyapatite. Four months after surgery the patient had no pain and
      had nearly full range of motion of the left knee. He was followed up for thirty
      five months with routine radiographs and physical examination. He had no
      recurrence, no pain, and regained full range of motion of his knee. Most
      chondroblastomas involve the medullary cavity; they may rarely involve the cortex
      but to the best of our knowledge, no cases with soft tissue involvement have been
      reported in the literature.

PMID- 14648961
TI  - Talus fracture associated with a fracture dislocation of the distal tibia in an
      immature skeleton.
AB  - A 12-year-old boy with a severe injury of his right ankle was treated in the
      accident unit. The local condition was an extensive open wound with parts of the
      fractured bones prominent. Radiographs showed a severely displaced fracture of
      the body of the talus associated with a Salter-Harris IV injury of the distal
      tibia and subluxation of the ankle. After proper debridement the fractured bones
      were reduced and fixed. Eleven years later both fractures are completely healed
      without any sign of avascular necrosis, the patient has full painless ankle
      movement and he can perform his demanding occupation without any problem.

PMID- 14648962
TI  - The protective effects of a new preparation on wound edges.
AB  - OBJECTIVE: This study investigated the effect of Cavilon No Sting Barrier Film
      (NSBF) (3M Healthcare) on erythema on the edges of highly exuding wounds in
      patients with venous stasis ulcers. METHOD: An intra-individual double-blind
      randomised test was performed on 239 patients. The two sides of each wound on
      each patient were treated with two different dressings: Cavilon NSBF was applied
      to the wound edges of one side and a control (water) to the edges of the other.
      Erythema was assessed daily using a chromameter. RESULTS: These are based on the
      227 patients who completed the study. The researchers were surprised by their
      unambiguity: in 88.1% of patients, the erythema completely disappeared within
      three days of treatment with the test material; in the remaining 11.9% it had
      completely disappeared after four days. With the control, erythema intensity
      remained more or less unchanged throughout the four-day observation period.
      CONCLUSION: This study demonstrates that Cavilon NSBF helped control erythema in
      all the patients: in 97.3% examined, the measurable and objectively recordable
      erythema receded within two days.

PMID- 14648963
TI  - Implementation of pressure ulcer guidelines: what constitutes a successful
      strategy?

PMID- 14648964
TI  - Comparison of different wound dressings on cultured human fibroblasts and
      collagen lattices.
AB  - OBJECTIVE: We compared the effects on cultured human fibroblasts of a new non
      adhesive wound dressing, Urgotul, with five other wound dressings. Urgotul is a
      hydrocolloid dressing; the comparator dressings included impregnated gauze and
      modern wound dressings. METHOD: Cultures in monolayer were used to study the
      morphology and growth of fibroblasts. The Bell model of cultured dermis
      equivalents was used to investigate myofibroblast differentiation. These cultures
      were labelled a-SM actin and F-actin. RESULTS: Two of the tested dressings
      induced cytotoxic effects. They were found to inhibit cell growth (greater than
      60%) and to disturb cell shape and cytoskeletal differentiation. Urgotul and the
      remaining three dressings showed no effect on proliferation. However, some of
      them modified fibroblast morphology and affected F-actin distribution.
      CONCLUSION: Depending on their nature and components, wound dressings may respect
      or affect fibroblast behaviour in vitro (proliferation, morphology and a-SM actin
      and F-actin distribution). The significance of these in vitro observed findings
      require further investigations.

PMID- 14648965
TI  - The cost-effectiveness of topical negative pressure versus other wound-healing
      therapies.

PMID- 14648966
TI  - Progress and consolidation. The future state of wound care.

PMID- 14648967
TI  - Should commercial companies provide practitioner education?

PMID- 14648968
TI  - A novel formulation of metal ions and citric acid reduces reactive oxygen species
      in vitro.
AB  - OBJECTIVE: Reactive oxygen species, including superoxide anions, are thought to
      play an important role in impairing wound healing. Additionally, superoxide
      anions react with nitric oxide produced by macrophages to form peroxynitrite,
      another strong oxidant with detrimental effects on surrounding tissue. This in
      vitro study investigated whether samples of metal ions and citric acid are able
      to reduce levels of reactive oxygen species. METHOD: Samples of materials were
      tested in assays for the following: inhibition of reactive oxygen species
      production by human polymorphonuclear neutrophils (PMNs); antioxidant activity
      (scavenging of superoxide anions in a cell-free system); inhibition of human
      complement (limiting the generation of complement factors that attract and
      stimulate PMNs, thereby reducing levels of reactive oxygen species). RESULTS:
      Metal ions were shown to inhibit both PMN production of reactive oxygen species
      and the activation of complement via the classical pathway, whereas citric acid
      was found to be a scavenger of superoxide anions. CONCLUSION: The beneficial
      effects of using formulations containing metal ions and citric acid on chronic
      wounds may be explained in part by a reduction of reactive oxygen species in
      these wounds.

PMID- 14648969
TI  - Silver dressings: the debate continues.

PMID- 14648970
TI  - [Male breast cancer].
AB  - Male breast cancer (MBC) is a rare disease, accounting for less than 1% of all
      breast cancers. It is an infrequent, but serious clinical problem. This paper
      discusses epidemiology, potential risk factors, tumor histopathology, clinical
      features and treatment strategies of the disease. Hormonal, genetic and
      environmental factors associated with an increased risk of breast cancer in men
      have been reviewed. Authors suggest that there may be an association between long
      term androgen therapy and breast cancer in men. This uncommon malignancy is most
      commonly seen in men over sixty years. Histologically MBC resembles that seen in
      women, although lobular cancer is rare in men. Tumors from men are more often
      estrogen-receptor positive. Treatment strategies draw from experience in women
      and usually begin with surgery. Modified radical mastectomy is the current
      treatment of choice for invasive cancer. Additional modalities include hormonal
      treatment, radio- and chemotherapy. Male breast cancer may be also a problem in
      the context of androgen replacement therapy during andropause.

PMID- 14648971
TI  - [Assessment of changes in levels of interleukin 6 and C reactive protein in
      patients with breast tumors].
AB  - Serum concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were
      determined in 74 patients with various histological types and clinical stages of
      breast carcinoma, recurrent breast carcinoma and of benign breast tumor. The
      concentrations of IL-6 and CRP were significantly increased in carcinoma patients
      relative to control group and to benign breast tumor group. The frequency of
      higher levels and absolute value of IL-6 and CRP showed tendency to significant
      increase with the stage of disease. A positive correlation was observed between
      the concentrations of IL-6 and CRP. Our results suggest that of IL-6 assay may be
      useful in estimation of progress disease in patients with breast carcinoma.

PMID- 14648972
TI  - [Evaluation of antioxidant status in patients with primary hepatocellular
      carcinoma].
AB  - The aim of this work was to evaluate the efficiency of the antioxidant system in
      patients with primary hepatocellular carcinoma. Total antioxidant status (TAS),
      superdoxide dismutase (SOD) and catalase (CAT) activity was examined in liver
      primary cancers and in blood serum of patients before and after surgery. In
      comparison with healthy liver, very low activity of TAS was observed in liver
      cirrhosis and in primary cancer. High activity of TAS in the blood serum of
      patients before and after surgery was comparable with TAS activity in blood serum
      of healthy persons. The highest activity of SOD and CAT was observed in liver
      cirrhosis. The lowest activity was observed in liver primary cancer. Activity of
      SOD and CAT in the blood serum of patients before surgery was higher than in the
      blood serum of patients after surgery. The highest activity was observed in the
      blood serum of healthy persons. Obtained results shows, that the dysfunction of
      the defensive antioxidant mechanisms have characterised with not only local
      disturbances (in the tumour cells region), but also circuital ones (blood). Low
      levels of the activity of TAS, SOD and CAT in patients with primary
      hepatocellular carcinoma indicate to the distortion of the oxidant--antioxidant
      balance and the decrease of organism antioxidant system efficiency. These
      observations show at the participation of free radical processes in the tumour
      pathogenesis.

PMID- 14648973
TI  - [Evaluation of diagnostic values of neoplastic procoagulant in pancreatic,
      hepatic and ovary cancers].
AB  - The cancer procoagulant (CP) activity has been evaluated in serum of patients
      with pancreas, liver and ovarian cancer and in homogenates of these cancer
      tissues. CP activity in examined cancer tissues as well as in blood serum was
      significantly higher than in the control. The obtained results indicate that
      estimation of CP activity may be useful in oncological diagnosis of pancreas,
      liver and ovarian cancer.

PMID- 14648974
TI  - [p53 protein in primary gastric carcinoma and coexisting metastases].
AB  - AIM: The expression of p53 protein was compared in primary gastric carcinomas and
      coexisting regional and distant metastases. The purpose of the study was to
      evaluate whether p53 staining in regional lymph-node metastases might improve the
      value of p53 as a prognostic marker and determine the behaviour of its protein
      during gastric cancer progression. MATERIAL AND METHODS: 60 gastric cancer
      patients were included into the study. In all patients the expression of p53 was
      assessed in primary tumours and in regional lymph-node metastases. Additionally
      in 12 patients the p53 expression was determinated in distant metastases. The
      number of all secondary tumours studied was 153. Formalin fixed, paraffin
      embedded material and three-stage immunohistochemical methods were used. RESULTS:
      p53 accumulation was detected in 24 (40%) of primary gastric carcinomas. In each
      patient p53 expression in primary regional and distant metastatic tumours was
      identical. CONCLUSIONS: Our results show that assessment of p53 in lymphnode
      metastases does not improve prognostic value of p53 in gastric carcinoma and
      support the view that p53 alterations occur before and maintain during metastatic
      spread.

PMID- 14648975
TI  - [Acute phase proteins in patients with cerebral infarction with or without a
      coexisting infectious disease].
AB  - The aim of the work was evaluation of influence of infectious process before and
      in first few days of cerebral infarction on concentrations of acute phase
      proteins (APP). We evaluated also dynamics of changes of APP and correlation
      between infection and clinical status and size of ischemia. We examined 47 sick:
      30 without infections and 17 with infectious process. Concentrations of C
      reactive protein (CRP) and fibrinogen in serum were estimated on 1, 3 and 7 day
      of infarction. Fisher's scale was used to evaluate patients' clinical status.
      Comparing to patients without infection, in patients with infection,
      concentrations of CRP and fibrinogen were higher in all days of investigation but
      dynamic of changes was different. The highest concentrations of APP in patients
      without infection were observed on 3 day of infarction (CRP 3.55 +/- 6.76 mg/dl,
      fibrinogen 425.7 +/- 117.9 mg/dl). In group with infection APP gradually
      increased and was highest on 7 day (CRP 7.91 +/- 9.28 mg/dl, fibrinogen 422 +/-
      119.5 mg/dl). Clinical status of patients with infection compare to patients
      without infection was heavier and the ischemic focus was larger. Infectious
      process coexisting witch infectious process influences on deterioration of
      clinical status and intensifies neurological disorders.

PMID- 14648976
TI  - [Three dimensional spiral computed tomography imaging in preop diagnosis of
      substernal goiter (preliminary study)].
AB  - The aim of the study was the estimation of substernal goiter by use of three
      dimensional spiral computed tomography (3-D sCT) with the contrast agent. The
      size and anatomy of goiter as well as its relation to surrounding tissues,
      particularly blood vessels was evaluated. The examination allowed good
      visualization of both inferior thyroid arteries. The use of 3-D sCT may have a
      great meaning in preoperative examination in particular in technically difficult
      cases of substernal goiter.

PMID- 14648977
TI  - [Does extracorporeal circulation during coronary artery bypass grafting damage
      vascular endothelium?].
AB  - The aim of the work was to study the influence of extracorporal circulation (ECC)
      on the vascular endothelial markers: von Willebrand factor (vWf), tissue
      plasminogen activator (t-PA) and trombomodulin (TM) in patients with coronary
      heart disease (CHD) undergoing coronary artery bypass graft (CABG). Examined
      group consisted of 30 patients (22 men, 8 women) at mean age 58.0 +/- 8.0 years,
      among them 19--were operated with ECC, 11--without ECC. Before and during
      operation blood was drawn 6 times. Control group consisted of 23. healthy
      volunteers at similar age. In the plasma vWf, t-PA and TM were determined with
      immunoenzymatic methods. Before operation the examined parameters were
      significantly higher compared to controls. The concentration of vWf during ECC
      was higher than in operation without ECC, but not significant. Differences
      statistically significant in the blood collected during ECC and without it
      appeared in t-PA only on the 3. and in TM on the 1. and 3. day after operation.
      It seems that ECC does not damage vascular endothelium direct, only indirect
      trough proinflammatory factors released from activated during ECC granulocytes
      and platelets.

PMID- 14648978
TI  - [Serum homocysteine, vitamin B12 and folic acid concentrations in patients with
      alcoholic liver cirrhosis].
AB  - The aim of the work was to establish serum homocysteine, vitamin B12 and folic
      acid concentrations in patients with alcoholic liver disease. Mentioned above
      vitamins are enzymatic cofactors for metabolic changes of homocysteine. It is a
      common fact that alcoholics often present with avitaminosis. Additionally,
      damaged liver worsens this pathology what can negatively influence metabolism of
      homocysteine. 40 patients--(mean age 52.7 years) and 40 healthy individuals (mean
      age 50.3 years) were examined. Hyperhomocysteinemia (concentration > 12 mmol//l)
      was stated in 50% of the patients and mean homocysteine concentration was
      statistically significantly higher if compared to the controls (13.29 +/- 8.16 vs
      11.03 +/- 1.6 mmol/l p < 0.05). In the female patients homocysteine concentration
      was significantly higher than in the healthy controls (14.6 +/- 10.63 vs 10.73 +/
      1.37 mmol/l p < 0.001). A negative correlation between homocysteine
      concentration and folic acid concentration in the group of the patients with
      hyperthomocysteinemia was observed (r = -0.88, p < 0.001) and among all the
      patients (r = -0.312, n.s.). Vitamin B12 levels were significantly higher in the
      group of patients than in the controls (659.43 +/- 489.27 vs 384.44 +/- 145.93 p
      < 0.001) what is consistent with the data from the literature. A positive
      correlation between mean homocysteine concentration, age and platelet count of
      the examined patients was stated (r = 0.350, p < 0.05, r = 0.508, p < 0.001). On
      the basis of the obtained results one can conclude that hyperthomocysteinemia is
      often established in alcoholic liver disease. Partially, low folic acid
      concentration is responsible for this fact. In theoretical deliberation one
      should consider estimation of betaine metylotransferasis levels--the enzyme which
      is responsible for homocysteine metabolism in the liver.

PMID- 14648979
TI  - [Nutritional status of patients in hospitals in Poland. I. Screening of adult
      patients].
AB  - The aim of the study was a screening assessment of the nutritional status of
      patients admitted to hospitals and discharged from hospitals. The study was
      carried out in 4 university hospitals, 4 woivodeship hospitals and 4 district
      hospitals. In randomly selected 3310 patients (every 10th patient admitted to
      hospital) anthropometric parameters were assessed: body height, body mass, body
      mass index (BMI), waist-hip ratio (WHR), arm circumference, blood morphological
      and biochemical parameters were determined (erythrocyte, white blood cell and
      lymphocyte count in blood, albumin and haemoglobin concentration in serum). The
      mean values of the assessed parameters in the whole studied population of
      patients admitted to various types of hospitals were not different from the
      normative values for adults, however, a gradual decrease of the values of certain
      parameters in the over 70 years age group was observed. Although, the mean values
      of the studied parameters of the nutritional status were within the accepted
      normal range, 10.43% of the studied patients had BMI below 20 kg/m2, and 20.7% of
      the patients the serum albumin level was below 3.5 g/dl on admission, which could
      suggest protein-energy malnutrition. In a yet higher proportion of patients (21%)
      lymphocyte count was below 1500/mm3. During hospital stay tendency became even
      more pronounced. On discharge from hospital the proportion of patients with BMI
      below 20 kg/m2 rose to 11.21%, and with serum albumin level below 3.5 g/dl rose
      to 28.6%. Only the proportion of patients with low lymphocyte count remained
      unchanged during hospital stay and was 21.1% on discharge. In the studied
      population 42.29% of the patients reported receiving of additional food beyond
      hospital diet.

PMID- 14648980
TI  - [Nutritional status of patients in hospitals in Poland. More thorough assessment
      of nutritional status of adult patients].
AB  - The purpose of the study was a more thorough assessment of the nutrition state of
      patients admitted to hospitals in Poland. The study was carried out in four
      hospitals at teaching centre level, in four hospitals at province level, and in
      four county hospitals. The patients for the study were selected randomly from
      3310 adult patients (every 10th patient admitted to these hospitals). For the
      study 210 patients (122 women and 88 men) were qualified. Their mean age was 54
      +/- 16 years (range 15-82 years). The patients were subjected to various
      biochemical tests including determination of antioxidant vitamins (vitamins A, E
      and C), vitamin B12, folic acid, ferritin, and homocysteine and blood lipids.
      Vitamin deficiency accepted as vitamin malnutrition was found in the case of
      vitamin C in 51.8% of the patients, folic acid in 32%, vitamin E in 10%, vitamin
      B12 in 6.8%, vitamin A in 1.4%. Vitamin deficiency was equally frequent in
      patients with malnutrition, overweight or with obesity. Lipid profile
      disturbances were found in 51% and high homocysteine level in 63% of the studied
      patients.

PMID- 14648981
TI  - [Concentration of procalcitonin and C-reactive protein in serum and erythrocyte
      sedimentation rate in active autoimmune diseases in children].
AB  - Procalcitonin (PCT), a 116 amino acid prohormon of calcitonin is a new acute
      phase reactant with features different to other markers of inflammatory response.
      The aim of the study was to compare PCT and C-reactive protein (CRP) levels and
      erythrocyte sedimentation rate (ESR) in active autoimmune diseases in children.
      PCT, CRP and ESR were determined in 28 children with active autoimmune process in
      course of various diseases: ulcerative colitis (n = 7), Lesniowski-Crohn disease
      (n = 2), juvenile chronic arthritis (n = 9), autoimmune haemolytic anaemia (n =
      4), dermatomyositis (n = 2), sklerodermia (n = 1), systemic lupus erythematodes
      (n = 1), Behcet's syndrome (n = 1), primary sclerosing cholangitis (n = 1). Serum
      PCT levels were measured by immunoluminometric assay, CRP by turbidometric assay,
      ESR was counted in millimetres after one hour. PCT exceeded 0.5 ng/ml in 5 cases
      (range: 0.0-2.4 ng/ml; mean: 0.4 +/- 0.1 ng/ml); CRP was above 0.5 mg/dl in 24
      children (range: 0.2-25.9 mg/dl; mean: 7.1 +/- 1.2 mg/dl); ESR was above 10 mm/h
      in all but 2 cases (range: 3-124 mm/h; mean: 57 +/- 7 mm/h). CONCLUSION: Contrary
      to CRP and ESR, serum PCT level in children with autoimmune diseases remains low.
      However in some children with highly active autoimmune process slight elevation
      of PCT concentration is observed without evidence of bacterial infection.

PMID- 14648982
TI  - [Familial cleft lip with or without coexisting cleft palate].
AB  - Etiopatology of clefts has not been explained yet. It is assumed that the cause
      of this defect is complex and heterogeneous. Genes which induce the incidence of
      cleft have not been detected too but clinical observations indicate a familial
      predisposition. At the Plastic Surgery Clinic of the Lodz Medical Academy, on
      years 1972-2001, 3180 children with cleft lip or/and palate were being treated.
      The group under examination consisted of 540 children with positive family
      histories. Two genetic groups were confirmed and each of them with a different
      risk of the reoccurrence of the defect. The first group--cleft lip and palate,
      the second group--an isolated cleft palate. A correlation between the type of
      cleft and a child's sex and its cleft affected parent was found. Among children
      of mothers with cleft lip there were 60% of boys and only 15% of girls with the
      same type of cleft. In mothers with cleft lip and palate the same type of cleft
      has been detected in 70% of boys and 18% girls. Similar results were obtained
      when affected fathers were taken into account. However, in case of mothers and
      fathers who were affected with isolated cleft palate there were significantly
      more girls than boys who had cleft palate. An in-depth study of cleft inheritance
      mechanisms will make in the future a more precise prediction of the occurrence of
      the defect in consecutive generations possible. Perhaps, the chance to work out
      cleft preventions will emerge and the gathered data will be taken advantage of in
      genetic counselling.

PMID- 14648983
TI  - [Mental problems in Lyme disease].
AB  - North-East of Poland is an area endemic for borreliosis. Psychiatric disorders,
      the most common for the late stage, are more and more frequent manifestations of
      Lyme disease. The aim of this study is to assess the incidence of different
      psychiatric complications and identify the spectrum of symptoms and
      psychopathological syndromes associated with Borrelia burgdorferi infection. Lyme
      disease causes a variety of psychiatric symptoms. They are less common in skin
      type of borreliosis manifested by skin erythema.

PMID- 14648984
TI  - [Contraceptive practices among students].
AB  - Research has shown that university students tend to have specific sexual
      behaviour. It is worth mentioning that not much attention has been paid to
      pregnancy prevention practices among medical students nor has any survey been
      conducted in this matter. The purpose of this survey was to ascertain the
      frequency of contraceptive usage among students at Medical University of Warsaw.
      Specially designed questionnaires were anonymously self-administered by 634
      female and 354 male medical students. 52.2% of the female students and 67.2% of
      the male students were sexually active at the time. 43.4% of the survey
      participants used condoms, while 26.3% used oral contraception pill (OCP) as
      contraceptive methods. Only 0.5% of those participants used intrauterine device.
      The survey result indicates an apparent dichotomy between the male and female
      students in terms of (appropriate) choice of the following contraceptive methods:
      condom, OCP, withdrawal, basal body temperature and Billings' methods.

PMID- 14648985
TI  - [Comparison of fat consumption by patients with large bowel adenomas and control
      group].
AB  - STUDY AIM: Analysis of differences in fat consumption (total fat, saturated,
      monounsaturated and polyunsaturated acids) and cholesterol between patients with
      large adenomas (study group, GB) and control group (GK). MATERIAL AND METHODS: GB
      and GK patients were recruited from the patients undergoing full colonoscopy
      during routine work of endoscopy unit. The whole material included 111 patients:
      57 patients with large bowel adenomas and 54 without large bowel adenomas. The
      intake of fat was assessed using a method calculating intake during 30 days
      preceding the study. RESULTS: In the group of studied women versus control group
      women no significant differences were found in consumption including energy value
      of diet (1755.8 kcal vs 1925.0 kcal), total protein (69.1 g vs 76.1 g),
      carbohydrates (237.2 g vs 258.0 g). Similarly, in the group of studied men no
      significant differences were found in the consumption of total protein (84.6 g),
      carbohydrates (275.7 g) and energy (2126.9 kcal) in relation to control group in
      which the respective values were: 98.4 g, 336.1 g and 2612.8 kcal. In the group
      of studied women the mean fat consumption was 67.2 g while in the control group
      it was 73.4 g. The mean intake of saturated fatty acids was 24.0 g and 25.2 g
      respectively. The consumption of monounsaturated and polyunsaturated fatty acids
      was in these group 27.1 g and 10.5 g vs 30.5 g and 11.9 g. The differences were
      statistically not significant. No difference was found in cholesterol intake
      between women in the study group and those in control group (245.8 mg and 280.0
      mg respectively). The male study group was not differing significantly from the
      control group in the consumption of total fat (83.6 g vs 102.3 g), saturated
      fatty acids (29.7 g vs 37.5 g), monounsaturated and polyunsaturated fatty acids
      (34.2 g vs 42.1 and 13.0 g 14.7 g) and cholesterol (335.0 mg vs 420.4 mg).
      CONCLUSION: No correlation was found between the consumption of total fat,
      saturates, monounsaturated and polyunsaturated fatty acids and the occurrence of
      large bowel adenomas.

PMID- 14648986
TI  - [Assessment of transforming growth factor-beta1 in serum of children with
      idiopathic nephrotic syndrome depending on the way of treatment].
AB  - The concentration of transforming growth factor-beta 1 (TGF-beta 1) in serum was
      performed by immunoenzymatic method in serum of children with nephrotic syndrome
      in following groups: group I--9 children (5-15 years) with focal segmental
      glomerulosclerosis (FSG), before Cyclosporine A treatment (CyA) (examination A)
      and after 3-6 months of Cyclosporine A treatment during remission (examination
      B), group II--13 children (5-14 years) with minimal change nephrotic syndrome
      (MCNS) during relapse (examination A) and after 7-20 days of prednisone
      (Encorton) treatment in dose 60 mg/m2, without the proteinuria (examination B),
      group III--15 healthy children (5-15 years). The aim of the work was to
      demonstrate any differences in concentration of TGF-beta 1 in serum of examined
      children and to show the influence of prednisone and Cyclosporine A on the
      concentration of TGF-beta 1. The results showed that before treatment increased
      concentration of TGF-beta 1 was shown only in children with MCSN (p < 0.05) and
      it was reverse proportional to albuminemia. However in children without
      proteinuria (B), the concentration of cytokines decreased in children with MCSN
      and increased in children with FSG treated with Cyclosporine A. CONCLUSION: The
      concentration of TGF-beta 1 in serum increases in children with nephrotic
      syndrome during gross proteinuria and hypoalbuminemia and after Cyclosporine A
      treatment.

PMID- 14648987
TI  - [The course of vulvar carcinoma in a 35-year old female patient].
AB  - A vulvar carcinoma is a malignant disease concerning women usually in their 7th
      or 8th decade of life. The course of this disease is very dynamic in young
      females. It is often diagnosed in the advanced stage, when it should be treated
      as a systemic disease. We present a case which is an example of a very sudden
      course, the diagnostic difficulty and the evidence of the systemic process of the
      disease. The case is a challenge to make an attempt to apply combined treatment
      in such cases.

PMID- 14648988
TI  - [Automatic blood pressure monitoring for verification of earlier diagnosis of
      treatment-resistant hypertension: a case report].
AB  - We present a case of 68-year old woman with long-term diagnosis of arterial
      hypertension resistant to treatment. Despite multiple treatment modifications and
      intensification the blood pressure values were poorly controlled. We observed the
      high lability of the blood pressure measured during 10 to 20 minutes intervals.
      24 h automatic blood pressure monitoring (ABPM) was performed using Holter's
      method. The examination revealed normal or even low values of the arterial blood
      pressure. We established diagnosis of "white coat effect" and corrected the
      therapy.

PMID- 14648989
TI  - [Tumor lysis syndrome in the course of acute lymphoblastic leukemia as the
      consequence of prednisone monotherapy].
AB  - Authors present the case of 15-year-old girl with diagnosed pre T-acute
      lymphoblastic leukaemia with hyperleukocytosis--at admission 213 x 10(9)/l. At
      clinical evaluation a major peripheral and abdominal lymphadenopathy, mediastinal
      mass, hepatosplenomegaly were revealed. After administration of prednisone for
      two times--11.4 mg/m2/24 h--the features of tumour lysis syndrome rapidly
      increased. Hyperphosphatemia, hyperkalemia and hyperuricemia resulted in acute
      renal failure. Renal replacement therapy was introduced with simultaneous
      application of cytoreduction phase therapy and induction of remission according
      to New York protocol. Total number of performed hemodialysis sessions was 12.
      Obtained haematological remission in 8th week of treatment is still present.
      Renal function remains normal. Remission supportive treatment has been continued
      according to above-mentioned protocol.

PMID- 14648990
TI  - [Atrial fibrillation: therapeutic strategies].
AB  - Atrial fibrillation is the most common tachyarrhythmia encountered in clinical
      practice. Atrial fibrillation is associated with other cardiovascular diseases
      and advancing age. Patients with atrial fibrillation suffer significantly higher
      morbidity and morality rates, leading to more hospitalizations and higher health
      costs. Treatment strategies for atrial fibrillation vary widely among clinicians.
      Two basic strategies are available, control of the ventricular rate with
      anticoagulation, and restoration and maintenance of sinus rhythm. It courts
      individualization of therapy in dependence on clinical situation and considering
      potential advantages and risk.

PMID- 14648991
TI  - [Neuropathological effects of surgical treatment of coronary heart disease].
AB  - Recent improvement in surgical and anaesthetic techniques has significantly
      reduced the number of post-operative complications, including those from the CNS.
      Nevertheless the risk of cerebral complications after cardiac revascularization
      by means of coronary artery bypass grafting (CABG) still exists and is considered
      an important risk factor in cardiac surgery. Organic cerebral complications may
      manifest themselves in the form of relatively overt neurological symptoms, such
      as stroke (1-3%), dysfunction of peripheral nervous system (5-10%) or slight,
      more difficult to diagnose cognitive deficits (33 to 83%). Acute qualitative
      dysfunction of awareness develops in about 7-12% of patients shortly after
      surgery. Depression or anxiety syndromes are observed in about 25% of patients.
      Presented results inevitably suggest a necessity for programmed psychological
      assistance and counselling in this category of patients.

PMID- 14648992
TI  - [Depression and anxiety after coronary artery bypass grafting].
AB  - The paper present results of last decade studies on mood and anxiety disturbances
      in patients who underwent coronary artery bypass grafting (CABG). Cardiovascular
      disease is currently the leading cause of death and morbidity in the
      industrialized world. CABG is the most common among surgical methods of its
      treatment. The incidence of mental disorders in patients after CABG is high. Its
      cause and pathogenesis are not clearly known. Depression is the risk factor of
      cardiovascular system diseases and also one of its causes. The heart operation
      itself is the strong stressful, life-threatening factor. The earlier course of
      cardiovascular disease and then heart surgery cause changes in style of life and
      combine with burdensome and arduous rehabilitation process. The social situation
      of the patients often deteriorates. Depression makes recovery difficult.

PMID- 14648993
TI  - [The laser irradiation effects on blood leukocytes: controversies and critical
      research findings].
AB  - Although much has been written in the recent years about usefulness of low and
      mid power lasers in medicine, many doubts still remain as to the actual
      effectiveness of such therapy, and in advance its impact on the leukocytes. Based
      on the detailed analysis in both Polish and foreign literature, the authors of
      the following paper present a great deal of doubts connected with safe
      application of the laser therapy. Presented full of controversies examples
      connected with the influence of the laser radiation on the leukocytes. The
      therapeutic effects of applied biostimulative lasers cannot be confirmed neither
      by practitioners nor by professional literature. It seems that critical and
      realistic attitude is necessary.

PMID- 14648994
TI  - [Retrospective analysis of post-endoscopic retrograde cholangiopancreatography
      mortalities].
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) which belongs to routine
      investigations of the biliary tract may lead to a possible development of various
      complications terminating occasionally in death. The authors analyses the causes
      of death in 6 patients (1.06%) who died following ERCP procedures performed for
      various reasons. They were solely woman. Deaths were most often caused by acute
      pancreatitis (in 3 cases), perforation of the duodenum, hemorrhage from the
      carcinoma of the ampulla of Vater, and acute cholangitis. Emphasis was laid on
      the significance of accurate and purposeful indications for performing ERCP. It
      was pointed out that the ERCP equipment intended for being used only once has
      been utilized many times for economic reasons. It is of the highest importance
      that the ERCP procedures are carried out in well equipped and specialized centers
      by adequately trained and highly experienced endoscopists.

PMID- 14648995
TI  - [Immune mechanisms in children with tuberculosis].
AB  - The easiness of pathological process spreading and difficulties with disease
      confinement are the most characteristic features of tuberculosis in childhood.
      These are mainly due to immaturity of both respiratory and immune systems. The
      infection with Mycobacterium tuberculosis gives rise to formation of granuloma, a
      product of macrophage accumulation, which develops due to proliferation of
      mycobacteria and remains a prominent pathogenic finding in Tbc. A functional
      equilibrium between the efficacy of cell-mediated immunity (necessary for
      eradication of the pathogens) and tissue-destructive delayed-type
      hypersensitivity reaction are observed in Tbc-infected individuals. IL-12 and IFN
      gamma, as strong activators of the Th1-driven immune response, are considered as
      crucial for successful eradication of Mycobacteria. The functional predominance
      of humoral immune response is a distinctive mark of immune response in childhood
      and is regarded as the risk factor associated with poor clinical outcome. The
      determinants have been shown of immune response against Mycobacteria with a
      special consideration of childhood Tbc.

PMID- 14648996
TI  - Insurance 101.

PMID- 14648997
TI  - So you have decided to become a dentist....

PMID- 14648998
TI  - Quick guide to buying insurance.

PMID- 14648999
TI  - About the Hawaii Insurance Division....

PMID- 14649000
TI  - Schedule your annual insurance check-up.

PMID- 14649001
TI  - An EPLI primer.

PMID- 14649002
TI  - About TDIC's EPLI coverage....

PMID- 14649003
TI  - Are you prepared for a workers' compensation claim?

PMID- 14649004
TI  - Disability needs change as dentists age.

PMID- 14649005
TI  - Facts about long-term care.

PMID- 14649006
TI  - Hog-housed!

PMID- 14649007
TI  - Magnet hospitals powerful force for excellence.

PMID- 14649008
TI  - March to Magnet.... one hospital's experience in achieving magnet status.

PMID- 14649009
TI  - Nursing in the NIS/CEE region. Its changing face.

PMID- 14649010
TI  - Nursing education: global perspectives.

PMID- 14649011
TI  - Global challenge: what if...?

PMID- 14649012
TI  - Shortage of nurse educators? It shouldn't come as a surprise!

PMID- 14649013
TI  - Coming of age in health care: changes, challenges, choices.

PMID- 14649014
TI  - The ND. Preparing nurses for clinical and educational leadership.

PMID- 14649017
TI  - Reflections on quality health care.
AB  - The author, a JCAHO Codman Award recipient, reflects on her professional career
      in the area of health care quality and describes how nurses have been leaders in
      the study and improvement of health care quality. Nursing's contributions to the
      development of quality of care measures, guidelines, and standardized languages
      are described and current and future opportunities for nursing are discussed.

PMID- 14649018
TI  - Claiming the future of nursing through nursing-sensitive quality indicators.
AB  - Although many of the changes in today's health care arena have been beneficial,
      there continues to be persistent dissatisfaction with the nation's health care
      delivery system. The provision of outcome-oriented, cost-effective health care is
      no longer a goal. It is a mandate. To accomplish this mandate, the relationship
      between the costs, quality and desired outcomes of care, and the processes
      involved in providing care must be reexamined. This article describes factors
      stimulating the American Nurses Association to develop nursing-sensitive quality
      indicators, details development of the National Database for Nursing Quality
      Indicators (NDNQI), and discusses the implications of nursing-sensitive
      indicators and NDNQI for nurse administrators. Nursing's quality indicators can
      be of value in the development of evidence-based health care report cards and can
      be used to direct change. We must move forward together in claiming the future of
      nursing through nursing-sensitive quality indicators.

PMID- 14649019
TI  - Improving physician documentation through a clinical documentation management
      program.
AB  - Improving physician documentation ensures that the patient's clinical course is
      clearly recorded. North Carolina Baptist Hospital implemented interventions
      addressing physician documentation to ensure the assignment of the most
      appropriate diagnosis-related group (DRG) when it launched the Clinical
      Documentation Management Program (CDMP). Collaboration between registered nurses
      trained as clinical documentation consultants (CDC) and certified coding
      specialists as well as ongoing physician education has resulted in more accurate
      and complete documentation in the medical record.

PMID- 14649020
TI  - The dynamics of curriculum design, evaluation, and revision. Quality improvement
      in leadership development.
AB  - The nursing shortage and specifically the shortage of new nursing leaders has
      fueled heightened recognition of the need for leadership development. This
      article considers the application of the quality improvement process to
      leadership curriculum development for the Center for Nursing Leadership's (CNL)
      Journey Toward Mastery program. Both the postmodernist approach and a commitment
      to scholarship are used as a framework to develop, evaluate, and revise the
      program. Further, the importance of symmetry between philosophical perspective
      and curriculum design are illustrated.

PMID- 14649021
TI  - Quality improvement processes in growing a service line. The myriad of
      opportunities.
AB  - The authors describe the evolution of a pediatric quality management program in a
      large community hospital that has rapidly grown in size and complexity to be a
      tertiary care center. Positive changes in senior leadership expectations,
      physician involvement, and training in performance improvement methodologies
      contributed to the development of a more comprehensive program. The authors from
      several specialty areas of the pediatric service illustrate three quality and
      performance improvement projects that they used in coping with the challenges of
      fast growth and higher acuity.

PMID- 14649022
TI  - Technology's implications for health care quality. A clinical engineering
      perspective.
AB  - Bill Gates states in Business @ The Speed of Thought that "the 2000s will be
      about velocity." This "decade of velocity" is driven by the flow of digital
      information. Health care organizations should develop a "digital nervous system"
      that is distinguished from a network of computers by the accuracy, immediacy, and
      richness of the information it brings to health care workers and by the insight
      and collaboration made possible by this information. This article provides a
      clinical engineering perspective on technology in health care in an era of rapid
      change. It discusses how clinical engineers work with health care professionals
      to manage and adapt to technological, economic, social, and regulatory forces
      that are redefining our approach to health care delivery.

PMID- 14649023
TI  - Le Bistro serves up cultural change.
AB  - Bristol Hospital, a 134-bed community health care system in Connecticut, has
      consistently been nationally ranked in the top tier of hospitals for its patient
      satisfaction scores. A key to this long-term distinction has been its commitment
      to a culture built around patient satisfaction and service excellence.
      Empowerment, vigilance, recognition, and celebration are the cultural
      cornerstones. The change has enabled the hospital to increase its market share,
      increase its satisfaction rankings, increase its employee retention, and enjoy
      consistent financial success.

PMID- 14649024
TI  - A collaborative perspective on nursing leadership in quality improvement. The
      foundation for outcomes management and patient/staff safety in health care
      environments.
AB  - By 2004, only organizations whose institutional operating strategies are built on
      a continual state of readiness and include performance improvement practices
      throughout the organization are going to successfully meet Joint Commission on
      Accreditation of Healthcare Organizations standards. As stewards of patient care,
      nurses maintain a unique role in identifying and guiding the intervention
      processes central to quality care, which prepares them to become key
      players/designers of a paradigm that demonstrates commitment to establishing and
      maintaining quality care. However, without recognition and support from
      organization leadership and physicians, the opportunity to effectively use the
      capabilities of nursing may be lost. The collaborative perspectives offered here
      attest to the fact that mutual belief and vision, coupled with creativity,
      strategic planning, and implementation, can effectively mobilize resources to
      establish priority measures and achieve quality patient/safety outcomes within
      the organization. Shifting the paradigm from just meeting the standards to
      continual readiness and performance improvement throughout the organization then
      becomes mission and mantra.

PMID- 14649025
TI  - Charting the course. A quality journey.
AB  - The development of a nursing quality program is particularly challenging in the
      face of building a new hospital, hiring and orienting 800 staff, purchasing
      supplies and equipment, writing policies, developing workflows and processes, and
      implementing an electronic medical record. This is the story of one hospital's
      journey. Strategies for success and lessons learned along the way are shared.

PMID- 14649026
TI  - Four elements of a successful quality program. Alignment, collaboration, evidence
      based practice, and excellence.
AB  - The nurse's role in quality improvement and assurance is well established, but
      this is particularly true as hospitals engage in a culture of patient safety and
      view quality-related activities as important "safety checks." The role of the
      nurse in ensuring quality related to patient care and safety cannot be
      overstated. The achievement of quality and safety in patient care is the result
      of caregivers doing the right thing the right way the first time. Nurses serve as
      a critical link to the best quality health care organizations have to offer. This
      article describes four elements of a successful quality program in a large
      tertiary health care setting (alignment, collaboration, evidence-based practice,
      and excellence) and makes the connection between quality and safety in the
      provision of exemplary patient care. Three examples are provided that show how
      nurses and other members of the health care team grouped together as a governing
      council for quality (Performance Improvement Council) and at the bedside as
      direct caregivers in ensuring patient safety and quality patient care.

PMID- 14649027
TI  - A magnet nursing service approach to nursing's role in quality improvement.
AB  - The heightened focus on quality and the rise of health care consumerism are
      manifestations of numerous interrelated dynamics, especially including the aging
      of the "baby boomers" and greater prevalence of chronic conditions, the explosion
      of biomedical scientific knowledge and technology, changes in prevailing methods
      of health care financing, a recent prolonged period of economic prosperity,
      widespread concerns about patient safety, return of disproportionate health care
      cost, and the democratization of medical knowledge consequent to widespread use
      of the Internet. Quality improvement in nursing was first introduced by Florence
      Nightingale during the Crimean War. Today, nursing quality continues to look at
      process, but has evolved to an emphasis on patient care outcomes. This article
      discusses nursing quality structure, processes, and outcomes at a large,
      teaching, tertiary medical center in Los Angeles, California. The medical center
      is one of two designated magnet nursing services in California. Nursing's role in
      achieving clinical and service quality for patients, communities, and staff are
      essential characteristics of magnet-designated nursing service organizations.

PMID- 14649028
TI  - The role of IT in health care quality assessment.

PMID- 14649029
TI  - Upstream solutions.

PMID- 14649030
TI  - Relevance of cues for assessing hallucinated voice experiences.
AB  - PURPOSE: To assess psychiatric nurses' views of the importance of itemized
      content represented on an Inventory of Voice Experiences (IVE) for ongoing
      assessment of atypical auditory sense perception in people who hear voices.
      METHODS: Over 6 months, 317 experienced psychiatric nurses rated 58 assessment
      cues for hallucinated voice experiences. Cronbach's alpha, Cohen's kappa, and
      Bartko's intraclass correlation coefficients were used to measure concordance of
      the nurses' judgments against two hypothetical standards derived for purposes of
      the study. FINDINGS: There was moderate support for both the internal consistency
      of the nurses' judgments concerning the importance of itemized content
      represented on the IVE and overall equivalence of the content. There was modest
      to-moderate concordance of the nurses' original and subsequent judgments but a
      lack of concordance of the nurses' judgments with equally weighted judgments of
      the principal investigator even though the judgments of the investigator were
      based on extant literature and published reports of voice hearers. CONCLUSIONS:
      Results may reflect the effects of repeated testing, but it also is possible that
      some nurses did not have enough knowledge or professional experience to quantify
      judgments about the importance of hallucinated voice descriptions tied to the
      items on the IVE. The findings are being used to refine the IVE. PRACTICE
      IMPLICATIONS: Findings provide nurses with opportunities for discerning specific
      characteristics, antecedents, and consequences of voice hearing along with their
      implications for health and well-being. Discernment of this information will
      facilitate identification of more specific and meaningful options for helping
      voice hearers manage their voices.

PMID- 14649032
TI  - Living through aneurysm.

PMID- 14649031
TI  - Critical thinking and accuracy of nurses' diagnoses.
AB  - Interpretations of patient data are complex and diverse, contributing to a risk
      of low accuracy nursing diagnoses. This risk is confirmed in research findings
      that accuracy of nurses' diagnoses varied widely from high to low. Highly
      accurate diagnoses are essential, however, to guide nursing interventions for the
      achievement of positive health outcomes. Development of critical thinking
      abilities is likely to improve accuracy of nurses' diagnoses. New views of
      critical thinking serve as a basis for critical thinking in nursing. Seven
      cognitive skills and ten habits of mind are identified as dimensions of critical
      thinking for use in the diagnostic process. Application of the cognitive skills
      of critical thinking illustrates the importance of using critical thinking for
      accuracy of nurses' diagnoses. Ten strategies are proposed for self-development
      of critical thinking abilities.

PMID- 14649033
TI  - In defence of the casual nurse.

PMID- 14649034
TI  - High blood pressure. Disease affects some five million Canadians.

PMID- 14649035
TI  - Does gowning prevent infection in the NICU?

PMID- 14649036
TI  - Distance-wise reflections for Ontario nursing.

PMID- 14649037
TI  - What's in a question?

PMID- 14649038
TI  - Personal accountability.

PMID- 14649039
TI  - Caring for the caregivers.

PMID- 14649040
TI  - Clinical, histological and microbiological study of hand-excavated carious
      dentine in extracted permanent teeth.
AB  - Changes in cultivable flora in dentine samples collected before and after hand
      excavation were examined in association with clinical status of the cavity
      surface, light microscopy and scanning electron microscopy (SEM). Thirty-five
      extracted permanent molar teeth with an occlusal caries lesion were excavated
      with hand instruments according to the atraumatic restorative treatment (ART)
      approach. Excavation pressure, dentine colour and consistency were recorded at
      the dentine-enamel junction (DEJ) prior to carious dentine removal and at the
      cavity floor after the final excavation; a microbiological sample of dentine was
      taken at both stages. Twelve restored teeth; six with positive and six with
      negative bacterial growth on the second sample, were selected for light
      microscopy and SEM. The hand-excavation removed tooth structure was soft,
      irreversibly damaged, dark and highly infected. Hand excavation reached dentine
      of increased hardness with a more normal colour to provide a sound structural
      base for restoration. Light and SEM examination of the cavity floor showed
      infected dentinal tubules in all 12 teeth examined. Linear logistic analysis
      showed a statistical association between light-yellow dentine on the cavity floor
      and an absence of bacterial growth (P = 0.006). This short-term in vitro study
      showed that caries-producing bacteria remained in dentine close to the cavity
      floor in 26/35 teeth despite clinical observations that indicated a suitably
      prepared cavity floor.

PMID- 14649041
TI  - Evaluation of a new method to achieve optimal passivity of implant-supported
      superstructures.
AB  - Statement of problem. Passive fit of implant-supported superstructures has been
      suggested as a prerequisite for maintenance of osseo-integration and for
      successful prosthetic reconstruction. PURPOSE: This study evaluated the degree of
      fit of superstructures cemented onto titanium abutments, compared to structures
      cast onto gold cylinders. MATERIAL AND METHODS: An impression was taken and a
      master cast made of five implants mounted in a stainless steel model. Six similar
      porcelain fused to metal superstructures with standardised dimensions were then
      fabricated. One group featured castings onto gold UCLA abutments, while in the
      other group the structures were cemented onto tapering titanium abutments.
      Vertical discrepancies between implants and both types of superstructures were
      measured on at six locations around each implant using a reflex microscope.
      Measurements were taken after securing the structures to the model with a single
      screw (torqued to 32 Ncm) placed in various locations and also after tightening
      all the retaining screws simultaneously to 10 Ncm. RESULTS: With the new single
      screw procedure, no significant difference in mean gap size was noted between the
      two groups. The discrepancies were significantly larger for certain screw
      locations (1 and 5), indicating that the one-screw test might be an inaccurate
      way of assessing fit. After tightening all the retaining screws simultaneously to
      10 Ncm, the mean gaps were 11.9 microns for the cemented group and 17.8 microns
      for the cast group. CONCLUSION: Although not statistically significant, cementing
      of superstructures onto titanium abutments improved the fit up to 50% compared to
      casting the structures onto gold UCLA-abutments. Tightening one terminal abutment
      screw and evaluating the discrepancies at the other abutments (one-screw test)
      distorted the results when evaluating the fit of long-span, implant-supported
      ceramo-metal superstructures. CLINICAL IMPLICATIONS: The results of this study
      indicate that cementing superstructures onto titanium abutments will lead to an
      improved degree of fit, compared to casting superstructures onto gold cylinders.
      In addition, the one-screw test may not be an accurate method of determining the
      level of passivity of long-span, ceramo-metal, implant-supported superstructures.

PMID- 14649042
TI  - A big issue about a little tissue.

PMID- 14649043
TI  - Modeling the professionally successful practice.

PMID- 14649044
TI  - Juvenile aggressive fibromatosis.
AB  - A case study of a fibromatosis occurring in a 3 year old male is discussed, where
      a clinical diagnosis of juvenile aggressive fibromatosis was reached after
      correlating clinical and histopathological findings.

PMID- 14649045
TI  - General practitioner's radiology case 14.

PMID- 14649046
TI  - Composite resin restorations--natural aesthetic and dynamics of light.

PMID- 14649047
TI  - Laboratory size and service: they're not mutually exclusive.

PMID- 14649048
TI  - Prosthetically oriented periodontal treatment in the aesthetic zone.

PMID- 14649049
TI  - Multidisciplinary treatment using a dermal matrix allograft material.

PMID- 14649050
TI  - The new patient experience--Part 4: The second visit.

PMID- 14649051
TI  - Contemporary ceramics for dentistry.

PMID- 14649052
TI  - Delayed and immediate loading of implants in the aesthetic zone: a review of
      treatment options.

PMID- 14649053
TI  - Is your spouse's smile aesthetic?

PMID- 14649054
TI  - Aesthetic considerations in the restoration of endodontically treated teeth.

PMID- 14649055
TI  - Current developments in magnification trends for improved visualization.

PMID- 14649056
TI  - AMIDE: a free software tool for multimodality medical image analysis.
AB  - Amide's a Medical Image Data Examiner (AMIDE) has been developed as a user
      friendly, open-source software tool for displaying and analyzing multimodality
      volumetric medical images. Central to the package's abilities to simultaneously
      display multiple data sets (e.g., PET, CT, MRI) and regions of interest is the on
      demand data reslicing implemented within the program. Data sets can be freely
      shifted, rotated, viewed, and analyzed with the program automatically handling
      interpolation as needed from the original data. Validation has been performed by
      comparing the output of AMIDE with that of several existing software packages.
      AMIDE runs on UNIX, Macintosh OS X, and Microsoft Windows platforms, and it is
      freely available with source code under the terms of the GNU General Public
      License.

PMID- 14649057
TI  - Effects of metalloporphyrins on heme oxygenase-1 transcription: correlative cell
      culture assays guide in vivo imaging.
AB  - Heme oxygenase (HO) is the rate-limiting step in the heme degradation pathway and
      is a potential target for the control, or prevention, of pathologic jaundice in
      neonates. Metalloporphyrins (Mps), a diverse set of synthetic derivatives of
      heme, can competitively inhibit the HO enzymes. However, certain Mps are
      phototoxic and some increase transcription of HO-1, the inducible HO isozyme.
      Therefore, effective development of this class of compounds as therapeutics for
      treating pathologic jaundice will require rapid and integrated biological screens
      to identify the most efficacious and safe Mps. To study the safety of these
      compounds, we assessed their cytotoxic effects and measured luciferase activity
      by bioluminescent imaging (BLI) as an index of HO-1 transcription, first in live
      cell cultures and then in living transgenic reporter mice. A total of 12 Mps were
      first evaluated in the correlative cell culture assay. Based on results from this
      study, 2 Mps, zinc protoporphyrin (ZnPP) and zinc bis glycol porphyrin (ZnBG),
      were selected for further studies in the live animal model. In vitro BLI showed
      ZnPP to be a strong inducer of HO-1 transcription in comparison to ZnBG, which
      showed minimal induction. Cytotoxicity studies revealed that ZnPP was phototoxic,
      whereas ZnBG had no effect on cell viability. In vivo BLI showed that both ZnPP
      and ZnBG had minimal effects on the levels of HO-1 transcription in the animals.
      Furthermore, serum enzyme assays indicated that neither caused detectable liver
      toxicity. These findings, and especially those with ZnBG, support the use of
      selected Mps as therapies for pathologic jaundice. Coupling the high throughput
      advantage of cell culture with the capability of imaging for whole-body temporal
      analyses could accelerate and refine the preclinical phases of drug development.
      Thus, this study serves as a model for understanding the effects of specific
      compounds in relation to defined targets using an integrated approach.

PMID- 14649058
TI  - Micro-MRI at 11.7 T of a murine brain tumor model using delayed contrast
      enhancement.
AB  - In vivo imaging methodologies allow for serial measurement of tumor size,
      circumventing the need for sacrificing mice at given time points. In
      orthotopically transplanted murine models of brain tumors, cross-section micro
      MRI allows for visualization and measurement of the physically inaccessible
      tumors. To allow for long resident times of a contrast agent in the tumor,
      intraperitoneal administration was used as a route of injection for contrast
      enhanced micro-MRI, and a simple method for relative tumor volume measurements
      was examined. A strategy for visualizing the variability of the delayed tumor
      enhancement was developed. These strategies were applied to monitor the growth of
      brain tumors xenotransplanted into nude mice and either treated with the
      antiangiogenic peptide EMD 121974 or an inactive control peptide. Each mouse was
      used as its own control. Serial imaging was done weekly, beginning at Day 7 after
      tumor cell implantation and continued for 7 weeks. Images obtained were
      reconstructed on the MRI instrument. The image files were transferred off line to
      be postprocessed to assess tumor growth (volume) and variability in enhancement
      (three-dimensional [3-D] intensity models). In a small study, tumor growth and
      response to treatment were followed using this methodology and the high
      resolution images displayed in 3-D allowed for straightforward qualitative
      assessment of variable enhancement related to vascular factors and tumor age.

PMID- 14649059
TI  - Functional imaging of proteolysis: stromal and inflammatory cells increase tumor
      proteolysis.
AB  - The underlying basement membrane is degraded during progression of breast and
      colon carcinoma. Thus, we imaged degradation of a quenched fluorescent derivative
      of basement membrane type IV collagen (DQ-collagen IV) by living human breast and
      colon tumor spheroids. Proteolysis of DQ-collagen IV by HCT 116 and HKh-2 human
      colon tumor spheroids was both intracellular and pericellular. In contrast,
      proteolysis of DQ-collagen IV by BT20 human breast tumor spheroids was
      pericellular. As stromal elements can contribute to proteolytic activities
      associated with tumors, we also examined degradation of DQ-collagen IV by human
      monocytes/macrophages and colon and breast fibroblasts. Fibroblasts themselves
      exhibited a modest amount of pericellular degradation. Degradation was increased
      4-17-fold in cocultures of fibroblasts and tumor cells as compared to either cell
      type alone. Inhibitors of matrix metalloproteinases, plasmin, and the cysteine
      protease, cathepsin B, all reduced degradation in the cocultures. Monocytes did
      not degrade DQ-collagen IV; however, macrophages degraded DQ-collagen IV
      intracellularly. In coculture of tumor cells, fibroblasts, and macrophages,
      degradation of DQ-collagen IV was further increased. Imaging of living tumor and
      stromal cells has, thus, allowed us to establish that tumor proteolysis occurs
      pericellularly and intracellularly and that tumor, stromal, and inflammatory
      cells all contribute to degradative processes.

PMID- 14649060
TI  - Evolving public perceptions of spaceflight in American culture.
AB  - There is a belief that exists in the United States about public support for
      NASA's activities. The belief is almost universally held that NASA and the cause
      of space exploration enjoyed outstanding public support and confidence in the
      1960s during the era of Apollo and that public support waned in the post-Apollo
      era, only to sink to quite low depths in the decade of the 1990s. These beliefs
      are predicated on anecdotal evidence that should not be discounted, but empirical
      evidence gleaned from public opinion polling data suggest that some of these
      conceptions are totally incorrect and others are either incomplete or more
      nuanced than previously believed. This paper explores evolution of public support
      for space exploration since the 1960s. Using polling data from a variety of
      sources it presents trends over time and offers comments on the meaning of public
      perceptions for the evolution of space policy and the development of space
      exploration in the United States.

PMID- 14649061
TI  - [Heartburn without esophagitis. Symptoms more important than the finding?].

PMID- 14649062
TI  - [Fatty liver. Not only ultrasound to be relied on!].

PMID- 14649063
TI  - [Before polyp removal. To stop or not to stop ASA?].

PMID- 14649065
TI  - [Cabbage leaf therapy of gonarthrosis. At first I smiled about white cabbage,
      then I tried it].

PMID- 14649064
TI  - [Digitalis -- poisoning, myopathy, ergotism.... When antibiotic and associated
      therapy become dangerous mixture].

PMID- 14649066
TI  - [Magnet instead of thread. New methods make easier the bypass-op].

PMID- 14649067
TI  - [Transcutaneous electric nerve stimulation and electronic muscle stimulation in
      athletic injuries. Pain patients under current].

PMID- 14649068
TI  - [Investigating pain in the shoulders, elbows and wrists. Skillful manipulations
      lead to diagnosis].

PMID- 14649069
TI  - [Wrist pain of uncertain genesis].
AB  - The leading symptom wrist pain may be caused by a number of different
      pathologies. These cover traumatic and non-traumatic changes to the bone
      (including primary arthrosis, chronic polyarthritis, aseptic bone necroses, e.g.
      Kienbock's disease). Other possible sources of pain may be the capsule/ligament
      structures of the wrist, the predominant condition in terms of incidence and
      severity being injuries to the scapholunar ligament. In young women in
      particular, differential diagnostic considerations should include instability of
      the wrist. The diagnostic work-up comprises history-taking, physical examination
      including function tests and a mandatory x-ray. An MR tomogram and interventional
      procedures (e.g. arthroscopy) where indicated, can provide additional
      information. At the center of the management plan is amelioration of pain and
      restoration of function. For this purpose, a range of curative or palliative,
      conservative or operative measures are available. Early referral to the hand
      surgeon may avoid secondary sequelae resulting from long-lasting complaints.

PMID- 14649070
TI  - [Leading symptom elbow pain. Differential diagnosis].
AB  - Pain affecting the elbow joint may be caused by a number of different
      pathologies. In principle, these can be grouped by causality criteria into
      degenerative causes, inflammatory causes, tumor disease, congenital disease and
      the sequelae of trauma. The majority of these latter are associated with typical
      clinical symptoms that can be established with the aid of a systematic clinical
      examination, history-taking, inspection, palpation, an examination of joint
      mobility, and finally radiography. In this way, the diagnosis can rapidly be
      established.

PMID- 14649071
TI  - [Leading symptom shoulder pain].
AB  - Pain in the shoulder should prompt a systematic clinical examination that adheres
      closely to the functional anatomy. The basic examination of the shoulder joint
      comprises active and passive movements and isometric resistance tests with the
      aid of which external and internal rotation and abduction/adduction can be
      investigated. The results of these tests provide the physician with a "pattern of
      findings" which unequivocally identifies the pain-triggering structure.
      Accordingly, shoulder pain can be classified into four categories as proposed by
      Cyriax. As treatment, intra-articular injections of corticoids or local
      anesthetics as determined by findings, where necessary supported by
      physiotherapeutic measures. Rupture of a tendon, in particular in the case of an
      active patient, is an indication for surgery.

PMID- 14649072
TI  - [Guidelines for the family doctor. Asthma: the only good patient is an instructed
      patient].

PMID- 14649073
TI  - [Controlled-release oxycodone -- a therapeutic option for severe neuropathic
      pain].

PMID- 14649074
TI  - [Ramipril after myocardial infarct. Long lasting cardiovascular protective
      action].

PMID- 14649075
TI  - [Further options with ramipril. Besides cardio- and nephro-protection diabetes
      prevention, too?].

PMID- 14649076
TI  - [New drug against lipid disorders. HDL level rises 30%].

PMID- 14649077
TI  - [Benign prostatic syndrome. 3-step plan for the treatment].

PMID- 14649078
TI  - [Widened indications. More latitude with insulin analogs].

PMID- 14649079
TI  - [Fast to the blood pressure goal. Lengthy dose adjustments harm compliance].

PMID- 14649080
TI  - [Anti-dementia agent helps mentally fit seniors, too. Compensated and errorless
      with Gingko].

PMID- 14649081
TI  - [Continuous protection against angina pectoris-like disorders. Attack prevention
      without a nitrate pause].

PMID- 14649082
TI  - [Pressure pain in the left epigastrium: blood picture provides diagnosis. Chronic
      lymphatic leukemia].

PMID- 14649083
TI  - [Dysuria].

PMID- 14649084
TI  - ["Breasts" after contra-sexual therapy].

PMID- 14649085
TI  - [Continuation 48. Sudden hearing loss: new guidelines for diagnosis and therapy].

PMID- 14649086
TI  - Our national health record. VistA is well on its way to meeting the requirements.

PMID- 14649087
TI  - Traveling in PACS. Web-based systems make images accessible at multiple
      locations.

PMID- 14649088
TI  - Hospital stock exchange. Reverse bidding, electronic catalogs and trading
      exchanges give buyers the key to the supply chain.

PMID- 14649089
TI  - Arrested development. Early medical management improves the outcomes of diseases,
      even chronic ones.

PMID- 14649090
TI  - IT buying guide. Tips from other professionals can help you make good decisions,
      avoid mistakes and get what you pay for.

PMID- 14649091
TI  - Standards at center stage. Safe, efficient care delivery depends on
      standardization.

PMID- 14649092
TI  - EHR trends and challenges. MRI's survey finds workflow and record access among
      top IT-manager concerns.

PMID- 14649093
TI  - Rx for safer ambulatory care. The adoption rate is low but potential is high for
      e-prescribing.

PMID- 14649094
TI  - Making your broker network more intelligent. Automated prospecting, quote
      generation and group enrollment give you a competitive edge.

PMID- 14649095
TI  - Mission-critical applications. Proactive monitoring can disclose technology
      service issues before they affect medical staff.

PMID- 14649096
TI  - Stalking. A perennial concern.

PMID- 14649097
TI  - Antimicrobial activity of extracts of local cough mixtures on upper respiratory
      tract bacterial pathogens.
AB  - The punched-hole and the paper disc diffusion methods were used in screening for
      the antimicrobial activity of six common ingredients used locally in cough
      mixtures, against the following bacteria: Klebsiella pneumoniae, Pseudomonas
      aeruginosa, Staphylococcus aureus. Enterococcus faecalis, Escherichia coli,
      Salmonella spp, Salmonella paratyphi, Shigella dysenteria, Shigella sonnei and
      Candida albicans. The results, evaluated as the diameter of zone of inhibition of
      microbial growth, showed that lime, garlic onion, onion and honey were active
      against Staphylococcus aureus, Streptococcus faecalis, Candida albicans,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Salmonella spp
      and Shigella dysenteriae. Bitter-kola nut extract and palm kernel oil showed no
      antimicrobial activities against any of the tested organisms. None of the
      extracts inhibited the growth of Salmonella paratyphi and Shigella sonnei and the
      most susceptible organisms were Escherichia coli and Salmonella spp.

PMID- 14649098
TI  - Dengue viruses in the Caribbean. Twenty years of dengue virus isolates from the
      Caribbean Epidemiology Centre.
AB  - The first isolate of a dengue virus in the Americas was obtained in Trinidad and
      Tobago in 1953, and several dengue virus isolates were obtained in subsequent
      years. However, the systematic isolation and typing of dengue viruses in support
      of virus surveillance and outbreak investigations did not start until the
      creation of the Caribbean Epidemiology Centre (CAREC) in 1975. Since then, over
      two thousand viral isolates have been obtained and typed from many countries in
      the English and Dutch-speaking Caribbean. In this communication, virological data
      from 17 countries between 1977 and 1996 are presented and analyzed together for
      the first time with available epidemiological data. Types 1, 2 and 4 were
      isolated over the period, and geographic and temporal patterns in the
      distribution of the most prevalent strains are presented. The historical
      surveillance data is critically assessed. A temporal correlation with reported
      dengue incidence and rainfall data in Trinidad and Tobago is reported. Recent
      changes in epidemiological patterns are described, including reference to two
      large later outbreaks. Risk assessment of complicated forms of dengue virus
      infections in the Caribbean has been attempted, with some success. The importance
      of ongoing systematic surveillance is discussed.

PMID- 14649099
TI  - Malaria in Guadeloupe (French West Indies) 1991-2000.
AB  - The only islands in the Caribbean that still have endemic malaria are Haiti and
      the Dominican Republic. Cases of imported malaria occur on the other islands,
      particularly Martinique and Guadeloupe, due to the movement of people to and from
      endemic regions that are geographically and/or culturally close. The re-emergence
      of transmission cannot be ruled out due to the local persistence of the potential
      vectors, the anopheles mosquitoes. This retrospective study, over a ten year
      period (1991-2000), included all of the cases of malaria confirmed by blood tests
      at Pointe-a-Pitre University Hospital. This hospital is the main healthcare
      facility in Guadeloupe. Fifty-nine bouts of malaria occurred in 56 patients. The
      annual incidence was estimated at 2 to 2.5 cases per 100,000 inhabitants.
      Plasmodium falciparum largely predominated, accounting for over 80% of cases. The
      only pernicious case observed resulted in the death of the patient. In all cases
      the patient had recently travelled to an endemic region, except in one case,
      caused by P ovale which has never been endemic in the Caribbean. African
      countries accounted for 43% of cases. No Asian or Pacific strains were
      identified. In all cases, anti-malarial drugs were not taken, taken incorrectly
      or were inappropriate. All of the cases of malaria reported in Guadeloupe in the
      last decade were imported and this region cannot be considered to be at risk of
      malaria infection. However, long-term epidemiological monitoring is necessary,
      together with specific entomological monitoring.

PMID- 14649100
TI  - Oral lichen planus. Clinical aspects and management in fifty-two Brazilian
      patients.
AB  - This study aimed to characterize the clinical profile of patients with oral
      lichen planus (OLP) and to evaluate the efficacy of topical, systemic and/or
      intralesional corticosteroids in the management of symptomatic cases. Fifty-two
      patients with OLP, 33 females and 19 males, aged from 17 to 75 years (mean 49.7
      years) were studied. Information regarding the clinical forms, sites of
      involvement, patients' medical history and habits were recorded. Diagnosis of OLP
      was made using clinical criteria alone in 32 cases, while biopsy examination was
      required in the remaining 20. Symptomatic lesions were seen in 29 patients, who
      were treated with corticosteroid. Asymptomatic cases (23) were only clinically
      monitored. The forms of OLP found in this study were reticular (47%), atrophic
      (24%), erosive (21%) and plaque-like (8%). The buccal mucosa was the site
      predominantly affected. Systemic diseases were found in 17 patients (seven
      diabetic and ten with hypertension) but these data lacked statistical
      significance (p > 0.05) when compared with a control group of age and gender
      matched patients without any type of mucocutaneous disease. A habit of tobacco
      and/or alcohol use was reported by 11.5% of the patients, most of them with the
      reticular form of the disease. Topical corticosteroid therapy alone was effective
      in producing relief of symptoms in 18 of the 29 patients, although some relapses
      occurred after discontinuation. For lesions non-responsive to topical treatment,
      intralesional injection and/or short-term use of systemic corticosteroids were
      used.

PMID- 14649101
TI  - Potential role for advanced trauma life support programme in improving trauma
      care in Jamaica.
AB  - Data from the Road Safety Unit in the Ministry of Transport and Works, Jamaica,
      show an increase in road traffic accidents from 7861 in 1991 to 11,010 in 1999.
      The average number of deaths annually was 380 +/- 48 (SD) while injuries averaged
      3320 +/- 262 per year. This represents an injury to death ratio of 8.7 compared
      with 24.9 for Trinidad and Tobago and 40 for Canada. During the period 1991 to
      2000, an average of 796 +/- 159 (SD) murders were committed annually. The number
      of murders increased by over 280 per cent between the decade of the seventies and
      the nineties. Data from the trauma registry of the University Hospital of the
      West Indies showed that 29.6 per cent of all admissions to the surgical ward
      between January 1998 and December 31, 2000, were due to injuries. There were 97
      deaths (3%) during this period and 33 occurred in the Accident and Emergency
      Department with 70 per cent occurring within 120 minutes of their arrival. The
      Advanced Trauma Life Support (ATLS) Programme emphasizes the resuscitation and
      stabilization of injured patients in the first few hours after injury. Most
      Emergency Departments in Jamaica are staffed by relatively junior medical
      officers and the low injury to death ratio among victims of motor vehicle
      accidents may be due to suboptimal care. Introduction of an ATLS programme in
      Jamaica may reduce the number of preventable deaths and also stimulate interest
      in trauma care thus increasing preventative measures to decrease the high
      incidence of trauma in Jamaica.

PMID- 14649102
TI  - Thymic surgery in Jamaica 1992-2000.
AB  - The treatment for thymic tumours and/or myaesthenia gravis (MG) includes
      thymectomy. Controversy exists as to the optimal timing and operative approach to
      thymectomy. At the University Hospital of the West Indies, Kingston, Jamaica, the
      results of thymic surgery during the period 1992 to 2000 were studied
      retrospectively. There were 26 patients operated on, 17 females and nine males.
      Twenty-three underwent thymectomy to treat MG, and three to remove a thymoma. The
      average age for females was 30.7 years, and 25.1 years for males. Average
      duration of symptoms prior to surgery was 16 months (all patients), and the
      interval between diagnosis and referral averaged 2.6 months. All patients
      underwent thymectomy via median sternotomy with a cervical extension of the
      incision if required. A policy of phrenic nerve preservation, even if residual
      tumour was left behind, was followed. Patients with thymomas were given post
      operative radiotherapy. Chemotherapy was not given to any patient. The medium and
      long term results of thymic surgery in a developing country are presented. The
      results are within international norms, although the small patient population
      makes statistical analysis difficult. There appears to be no need to change
      current practice, despite the reported efficacy of less invasive approaches to
      thymic surgery.

PMID- 14649103
TI  - Six-month hypertension intervention study. One year follow-up.
AB  - The aim of this study was to assess the long term impact of an educational and
      monitoring intervention on blood pressure control in patients (n = 80) who had
      blood pressure > 140/90 mm Hg in January 1999, and attended the Specialist
      Hypertension Clinic, the University Hospital of the West Indies. Forty-two of
      these patients (cases) attended the monthly educational and monitoring
      intervention for six months, in addition to their usual care. The other 38
      (controls) attended only one educational intervention at the end of the six
      months. One year later, patients were traced by telephone or clinic attendance.
      Data were collected on 73 (91%) patients, 40 (95%) cases and 33 (87%) controls by
      clinic records or by direct measurement of blood pressure and weight. Three
      (7.5%) cases and two (6%) controls had died. One (2.5%) case and five (15%)
      controls had been referred to renal or cardiac clinics. Twenty-five (59.5%)
      cases, and 14 (36.8%) controls were still attending the clinic. At the end of the
      year, 26% (7/27) of the cases and 30% (6/20) of the controls had blood pressure
      (BP) controlled to < 140/90 mm Hg. These proportions compare to 28% (11/39) cases
      and 22% (8/36) controls at the end of the six-month intervention. At the end of
      one year, neither cases nor controls showed significant mean changes in BP,
      weight, nor body mass index (BMI). There was no significant difference between
      the median BMI of the cases, 31.2 kg/m2 and that of the controls, 29.3 kg/m2.
      Seventy-seven per cent (21/27) cases and 84.2% (16/19) controls had BMI > 25
      kg/m2. These data, though limited, are consistent with reports that the impact of
      lifestyle interventions in chronic diseases may be short lived. This study
      suggests that therapeutic lifestyle intervention strategies need to be integrated
      with the overall management of patients so that the effect may be sustained.

PMID- 14649104
TI  - Depression and anxiety in hypothyroidism.
AB  - The aim of the study was to determine the prevalence and severity of depression
      and anxiety in patients with hypothyroidism and to compare this with euthyroid
      patients. Thirty patients with hypothyroidism and 30 euthyroid controls attending
      the Endocrinology outpatient department of Celal Bayar University, Medical
      Faculty were included in the study. The hormonal screening was done by
      immunoassay and haemagglutination methods. Then, for psychiatric assessment,
      Hospital Anxiety and Depression Scale (HAD), Hamilton Depression Rating Scale
      (HAM-D), and Hamilton Anxiety Rating Scale (HAM-A) were used. There was no
      difference between the two groups in terms of demographic features. Total scores
      obtained from the scales used in the study did not differ significantly (p >
      0.05). The frequency of items of both HAM-D and HAM-A did not show any
      differences in the two groups. By Wilks' Lambda discriminant analysis, depressive
      mood (HAM-D#1) was found to be the discriminating feature between the hypothyroid
      group and the euthyroid group. Therefore, depression and anxiety were not
      outstanding features in hypothyrodism. However, depression was more significant
      in the hypothyroid than euthyroid group.

PMID- 14649105
TI  - Decrease in the incidence of tetracycline resistance in strains of Neisseria
      gonorrhoeae in the nineties.
AB  - Antibiotic resistance determined by standard disc-diffusion method on GC agar
      with supplement B in 583 strains of Neisseria gonorrhoeae encountered between
      1991 and 1996 at the University Hospital of the West Indies, Kingston, Jamaica,
      were analyzed. The level of penicillin resistance varied between 40% and 28% over
      the years. Tetracycline resistance fell from 44.2% in 1991 to 23.9% in 1996.
      Twenty-one per cent of the isolates were resistant simultaneously to both
      penicillin and tetracycline in 1991. The percentage of such strains decreased to
      6.5% in 1996. Ceftriaxone was introduced as a first line drug in treatment of
      gonococcal infections in the late 1980s. The declining trend of tetracycline
      resistance may be due to a decrease in the usage of tetracycline in recent years.

PMID- 14649106
TI  - A case control study of the prevalence of perinatal complications associated with
      fetal macrosomia in Antigua and Barbuda.
AB  - The prevalence of obstetric, perinatal and neonatal complications associated with
      fetal macrosomia at Holberton Hospital in Antigua and Barbuda was assessed by a
      retrospective, case-control study. All babies of birthweight (BW) greater than
      4.5 kg born between July 1991 and January 1997 and all babies with BW greater
      than 4.0 kg born between July 1991 and January 1995, were included. Control
      babies, were selected from those born on the same day as the index case. Babies
      of BW > 4.0 kg and babies of BW > 4.5 kg were 5.7% and 1% of births respectively
      Records were complete for 157 large babies (40 with BW > 4.5 kg) and 157 control
      babies < 4.0 kg. Mothers of large babies were significantly older, more parous,
      more likely to have diabetes mellitus, hypertension, and deliver after 40 weeks
      gestation. At delivery, mothers of large babies were more likely to bleed. Large
      babies had lower one minute and five minute Apgar score, were more likely to be
      meconium stained, have respiratory distress, have birth trauma or dystocia and to
      be admitted to Special Care Nursery. There was no difference in Caesarean section
      rate, hospital days, neonatal jaundice or mortality. Babies with BW > 4.5 kg had
      mortality of 7.5% versus 1.8% for those < 4.5 kg. Fetal macrosomia remains a
      difficult obstetrical problem associated with significant maternal, perinatal and
      neonatal consequences. Morbidity and mortality are still significant in developed
      and developing countries alike.

PMID- 14649107
TI  - Infective endocarditis at the University Hospital of the West Indies. A revisit.
AB  - Many countries have reported a change in the profile of infective endocarditis
      (IE) over the past three decades. The objective of this study was to evaluate the
      characteristics of IE from the autopsy service of the University Hospital of the
      West Indies (UHWI) during the last 15 years and to compare the results with that
      of an earlier study. There were 26 cases of IE during the period under review
      with a M:F ratio of 1.2:1. The ages ranged from 15 days to 74 years with a mean
      of 36.4 +/- 24.57 years. The largest number of cases (n = 7) occurred in the 10
      to 19-year-age group. Cardiac predisposing factors were identified in 14
      patients; nine with rheumatic heart disease, four with prosthetic valves and one
      with a bicuspid aortic valve. All vegetations were located on valves, the aortic
      being the most frequently involved followed by the mitral. Streptococcus species
      were the most common causative organisms followed by Staphylococcus aureus.
      Compared with the profile seen 15 years ago, there have been only minor changes
      in the characteristics of IE cases observed in the autopsy service at the UHWI.

PMID- 14649108
TI  - Image and diagnosis. Congenital diaphragmatic hernia.

PMID- 14649109
TI  - Free vascularized fibula graft for a cystic femoral head and neck lesion in the
      West Indies.
AB  - A case is presented of an 18-year-old athlete with fibrous dysplasia of the
      femoral neck and head. The approach was by joint plastic and orthopaedic teams,
      which minimized operating time and allowed the option of vascular bone grafting.
      The lesion was curetted through a greater trochanteric window and the defect
      reconstructed with a free vascularized fibula graft with excellent result. Weight
      bearing was achieved in six months and there was minimal donor site morbidity. We
      believe the free vascularized fibula graft to be a reconstructive option, in
      difficult orthopaedic problems, facilitated by microsurgery and there is immense
      benefit of a joint effort between the orthopaedic and plastic surgical teams.

PMID- 14649110
TI  - Recent upsurge of tuberculosis in paediatric admissions at the University
      Hospital of the West Indies.
AB  - These case reports describe the clinical course of eight children who were
      admitted to the University Hospital of the West Indies, Kingston, Jamaica,
      between July 2000 and November 2001 because of a diagnosis of tuberculosis. This
      represented an increase in the incidence of the disease in children at this
      institution. The purpose of this report is to make healthcare workers aware of
      the resurgence of tuberculosis. The diagnosis of paediatric tuberculosis is
      challenging and requires a high index of suspicion in the presence of suggestive
      clinical and laboratory findings. The diagnosis should not be limited to the
      immunocompromised patient, as in this report the majority of the patients were
      HIV negative.

PMID- 14649111
TI  - A case of pulmonary lymphangioleiomyomatosis.
AB  - A case of pulmonary lymphangioleiomyomatosis (PLAM) occurring in a 48-year-old
      Jamaican female is presented. The clinical, radiological, and pathological
      findings are typical of this rare condition, and serve to emphasize the need for
      a high index of suspicion in order to make the diagnosis and commence therapy
      early in the course of the disease. The outlook for patients with PLAM continues
      to be poor.

PMID- 14649112
TI  - Bilateral epididymal metastases from primary adenocarcinoma of the prostate.
AB  - A 65-year-old man diagnosed with adenocarcinoma of the prostate gland opted for
      hormonal manipulation and had bilateral orchiectomy. Histological evaluation
      showed tumour deposits in both epididymides. Despite the relatively common
      occurrence of adenocarcinoma of the prostate, epididymal metastasis is a rare
      occurrence. This case highlights the need for proper evaluation of the testes and
      para-testicular structures so that accurate staging of these tumours can be made.

PMID- 14649113
TI  - Subepidermal calcified nodule.
AB  - Subepidermal calcified nodules are rarely seen and are classified under
      idiopathic subepidermal calcifications. They commonly affect children. It is most
      frequently encountered in the face, and it is less common in the extremities.
      Here, we present a case where the lesion was localized on the knees of a 23-year
      old female patient.

PMID- 14649114
TI  - Complex regional pain syndrome.
AB  - A previously well fifty-five year-old female household helper developed complex
      regional pain syndrome Type II (reflex sympathetic dystrophy) following a minor
      injury to her left hand. She had marked hyperaesthesia and allodynia and was
      unable to perform her household work and to participate in the required
      physiotherapy. Following a series of stellate ganglion block, neurostimulation as
      well as physical therapy, there was a dramatic improvement in her condition and
      she was able to return to normal function.

PMID- 14649115
TI  - Hyperglycaemic hyperosmolar syndrome in young obese Afro-Caribbean adults--a
      diagnostic dilemma. Report of two cases.

PMID- 14649116
TI  - Cardiac biomarker usage in the West Indies.

PMID- 14649117
TI  - Undelayed femoral head ossification in Kniest dysplasia. Evolution of hip
      abnormalities, 30-year follow-up.

PMID- 14649118
TI  - Testing migrant workers for communicable diseases.

PMID- 14649119
TI  - Disaster planning.

PMID- 14649120
TI  - Introduction to pulse oximetry.

PMID- 14649121
TI  - Effective theatre scheduling. The Derby Theatre Project experience.

PMID- 14649122
TI  - Redefining perioperative advanced practice. The nurse specialist in anaesthesia
      and emergency surgery. Part I. Defining the problem and providing a solution.
AB  - The development of the specialist nursing role was born out of an honest and
      clinically-driven review of the system that emergency patients experienced. The
      approaches taken during this review consistently returned facts that this pathway
      was less than optimal, and a great many improvements could be made. It is
      important to identify at this stage that simply adding more resources, i.e.:
      theatre space and beds, would not have improved the patient's experience. The
      pathway needed greater continuity and better co-ordination. This required a great
      deal of cooperation between clinical and managerial staff, including some
      fundamental re-examination of traditionally held beliefs about the role that
      perioperative nursing could have in managing this patient group. Part Two of the
      paper (Radford et al 2003) will present the details of how the development of
      this post challenged the care delivery system for emergency surgical patients.
      Particular reference will be made to the scope of practice, clinical and
      organisational impacts and future directions.

PMID- 14649123
TI  - An audit of the skin condition and epidural dressings.

PMID- 14649124
TI  - The first assistant. The perspective from a district general hospital.

PMID- 14649125
TI  - Combating the nursing shortage. Vermont's call to action.
AB  - This article describes the centrality of the nursing leadership role in Vermont's
      statewide efforts to combat the nursing shortage, particularly the establishment
      of a Blue-Ribbon Commission and an Office of Nursing Workforce Research,
      Planning, and Development. Recommendations by the Blue-Ribbon Commission along
      with its progress to date are presented. The role of the Office of Nursing
      Workforce Research, Planning, and Development is described in accomplishing the
      recommendations of the Blue-Ribbon Commission. These efforts have been
      cumulative, characterized by innovation and unprecedented collaboration between
      stakeholders representing nursing, public health, health care administration,
      education, and the political and private sectors. Lessons for replication are
      underscored.

PMID- 14649126
TI  - Tackling the nursing shortage in rural America. Linking of education and service
      in a differentiated practice environment.
AB  - The need for solutions to the nursing shortage in rural areas, teamwork, and new
      ways of thinking about management and nursing education prompted the development
      of an innovative clinical activity in a rural hospital that utilizes a
      differentiated practice nursing model. The activity is part of a project titled
      University and Community College Partnership in Education (supported by a grant
      from the Fund for Improvement of Postsecondary Education). The activity links
      baccalaureate students at a mid-western university with associate degree students
      at a rural community college to study the management model in a two-day immersion
      clinical experience.

PMID- 14649127
TI  - A rural state's response to the nursing shortage. Nevada's story.
AB  - This article describes how the nursing leadership in Nevada is responding to the
      nursing shortage crisis. The Nevada Hospital Association and Nevada legislature
      have supported statewide educational initiatives. Outcomes of a task force
      include recommendations to improve articulation agreements between schools of
      nursing and community colleges, external funding for summer salaries for faculty,
      efforts to recruit and retain minority and other nontraditional students,
      reallocation of financial resources among all universities and colleges in the
      state, reexamination of state-mandated faculty-to-student ratios, and changes in
      the work environment to encourage nurses to remain in the profession. A plan was
      developed to double enrollments in nursing schools through federal and state
      funding strategies, creative scheduling, and academic resource support.

PMID- 14649128
TI  - A specialty organization addresses the nursing shortage.
AB  - The Association of periOperative Registered Nurses (AORN) has committed
      organization resources to address the worsening shortage of qualified
      professional registered nurses in the operating room. Organizationally, the
      efforts have addressed assisting members to recruit new staff and provide
      orientation and educational experiences that prepare competent practitioners for
      this specialty. As well, the organization has developed educational programs,
      membership programs, and other services to support AORN members to develop
      mentoring relationships with students and new staff. Other organizational efforts
      include legislative activities and collaborative relationships with other
      organizations.

PMID- 14649130
TI  - Addressing the shortage. Strategies for building the nursing workforce.
AB  - For more than two decades, nursing educators and administrators have grappled
      with issues of declining student enrollments and the concurrent "defection" of
      nurses from the labor market. This article describes both short- and long-term
      strategies for addressing the nursing shortage and identifies new opportunities
      for collaboration in building the nursing workforce of the future.

PMID- 14649129
TI  - A collaborative effort between nurse leaders to address the hospital nursing
      shortage.
AB  - The current nursing shortage is not a routine swinging of the supply pendulum.
      Indeed, this shortage is determined to be quantitatively and qualitatively
      different from those of the past (Kimball & O'Neil, 2002). In Cincinnati, Ohio,
      nurse leaders decided that the uniqueness of this shortage necessitated new
      strategies. Hospital nurse executives proposed the creation of a community
      leadership group, and other Cincinnati nurse leaders enthusiastically embraced
      the idea. A collaborative effort was initiated in the spring of 2000 between a
      representative group of hospital chief nursing officers, school of nursing deans
      and faculty, staff nurses, hospital nurse recruiters, and professional nursing
      organizations to address concerns related to the nursing shortage. This article
      describes the process and outcomes of this collaborative effort with a focus on
      the retention of hospital nurses.

PMID- 14649131
TI  - Career development programs at Landspitali University Hospital.
AB  - Restructuring nursing services following a hospital merger has an impact on
      retention. A career development program for nurses can be an effective retention
      strategy. Data were gathered from three focus groups of practicing nurses and an
      e-mail survey of students in the graduating nursing class. Based on their
      responses, a new career development structure was proposed. The structure
      involves three levels of development that provide an opportunity for registered
      nurses to grow in and expand their careers. The General Internship Program is
      geared toward new graduates and establishing a career. The Specialty Internship
      Program provides knowledge and skills in specialized nursing, and the Service
      Focused Cross Training Program allows nurses to expand their skills and focus
      their practice on one patients population.

PMID- 14649132
TI  - Is the US draining the UK of nurses?

PMID- 14649133
TI  - Improving the patient experience.

PMID- 14649134
TI  - A health website for children.
AB  - Knowledge about the special needs of children and adolescents in hospital has
      advanced in the past 40 years. There is now general acknowledgement that they
      should have services tailored to their emotional and developmental needs, and
      should be cared for by specially trained practitioners. However, admission to
      hospital is a stressful experience even for those going into the most child
      friendly environments. Preparation can do much to relieve anxiety, and a new
      website has been set up to give children the information they need about their
      health and what to expect in hospital.

PMID- 14649135
TI  - Understanding eating disorders.
AB  - Eating disorders can be severe and enduring mental illnesses that have serious
      physical, psychological and social consequences. They can also have a significant
      effect on the person's friends and family. In this patient group, control of body
      shape, weight or eating is over-valued and becomes the main or only way of
      judging self-worth. Eating disorders can be mild and self-limiting, but they
      commonly run a chronic course unless treatment is successful. Nurses play an
      important role in early detection, assessment and treatment.

PMID- 14649136
TI  - What you need to know about ... gallstones.

PMID- 14649137
TI  - Setting up and evaluating patient information open evenings.
AB  - Staff at the Victoria infirmary patient preadmission clinic for major joint
      replacement surgery recognised that the amount of information patients are given
      before a procedure is impossible to retain. This can lead to patients feeling ill
      informed and less confident in their health care providers. An open evening was
      arranged to provide patients, accompanied by a friend or relative, with access to
      information on all aspects of their journey of care, while giving them the
      opportunity to meet staff and ask questions. The success of the event has
      resulted in it becoming a regular occurrence.

PMID- 14649138
TI  - Psychosocial issues relating to external fixation of fractures.
AB  - The use of external fixation devices has become increasingly popular for the
      treatment of fractures and for limb reconstruction procedures. This article
      reviews the nursing literature that examines psychosocial issues in the context
      of treatment with external fixation. Nearly all the evidence cited is anecdotal.
      Personal experience should not be ignored, but this review exercise highlights
      the lack of research-based evidence to back up provision of care in what is a
      fundamentally important aspect of the patient experience.

PMID- 14649139
TI  - Health tourism. The dilemma for nurses.

PMID- 14649140
TI  - 'The patients are delighted at how quickly they have healed'. Interview by Leona
      Armstrong.

PMID- 14649141
TI  - Improving access to essential equipment.

PMID- 14649142
TI  - Intermittent self-catheterisation.
AB  - Intermittent self-catheterisation (ISC) has reduced infection hazards and greatly
      improved the lives of many patients with micturition disorders. The technique is
      used by male and female patients who experience neurogenic bladder dysfunction or
      voiding difficulties. Some of the most beneficial results associated with ISC
      have been reported when the technique is used by people with spina bifida,
      paraplegia or multiple sclerosis. ISC is the preferred course of management for
      patients with a hypotonic bladder (a floppy bladder that is unable to contract
      partially or totally during the micturition cycle).

PMID- 14649143
TI  - Indwelling catheters: developing an integrated care pathway package.
AB  - Urinary catheterisation is a common nursing procedure in hospital and in the
      community, yet there are risks associated with it. Complications include urethral
      trauma, urinary tract infection, strictures, urethral perforation, encrustation,
      bladder calculi and neoplastic changes (Lowthian, 1998). The procedure is also
      linked to nosocomial infection and, in some cases, these catheter-related
      infections can prove fatal (Pratt et al, 2001). Due to the risks, catheterisation
      is indicated as a last resort after all other interventions have failed.

PMID- 14649144
TI  - Rehabilitation and continence promotion following a stroke.
AB  - About 100,000 people in England and Wales experience a stroke each year. Nine out
      of ten strokes affect people aged over 55 years and 300,000 people are living
      with disability caused by stroke. About a third of people who experience a stroke
      will die within the first year, one third will make a good recovery and the final
      third will experience moderate to severe disabilities (Westcott, 2000).

PMID- 14649145
TI  - The benefits of a lending library for female urinals.
AB  - Reduced mobility, physical weakness or other disabilities can all contribute to
      continence problems (McIntosh, 1998). The ability to transfer from a bed or chair
      to a commode may be a critical factor in deciding whether patients can be
      discharged home or into residential care. Also, patients--particularly women--may
      be prescribed continence pads simply because they cannot access the toilet or
      commode rather than having a diagnosed bladder condition.

PMID- 14649146
TI  - Admission avoidable?

PMID- 14649147
TI  - Standard life.

PMID- 14649148
TI  - Proud and 'exceptionally nice'.

PMID- 14649149
TI  - Promoting continence in nursing homes: responding to government guidelines.

PMID- 14649150
TI  - Frail older people: participation in care.

PMID- 14649151
TI  - Sundowning in older people with dementia: evidence base, nursing assessment and
      interventions.
AB  - Sundowning is a phenomenon infrequently discussed in UK nursing literature but is
      a serious cause of distress for many older people and their carers. This article
      addresses some of the causes of sundowning and suggests ways in which nurses may
      contribute to better management of the condition.

PMID- 14649152
TI  - Age of reason.

PMID- 14649153
TI  - Support act.

PMID- 14649154
TI  - Emergency measures. Interview by Elizabeth Lynch.

PMID- 14649155
TI  - Hands-on guidance.

PMID- 14649156
TI  - Golden oldies.

PMID- 14649157
TI  - Media mania.

PMID- 14649158
TI  - Reawakening awareness.

PMID- 14649159
TI  - The real fright club.

PMID- 14649160
TI  - Assessment of portfolios in professional education.
AB  - Student-centred methods are increasingly being used to carry out learning,
      teaching and assessment activities in professional education. These methods
      underpin current curriculum design, and evidence suggests that they have been
      successful in reducing the perceived theory-practice gap and making professionals
      fit for practice in the chosen discipline. A portfolio is a common method of
      assessment in many programmes. A tripartite approach to assessing the portfolio,
      involving the student and his or her practice supervisor in the assessment
      process, brings together the assessment of theory and practice, and makes the
      process even more transparent. The tripartite approach to assessing portfolio is
      used in the mentorship preparation programme at the author's university, which
      also prepares the student to become an assessor. Thus the assessment process
      becomes part of the learning experience and is valued by the tutor, student and
      practice supervisor. This article describes a small-scale study carried out with
      a colleague on the use of portfolios as a tool for assessment in a short
      programme via a tripartite approach involving the practice supervisor, student
      and tutor.

PMID- 14649161
TI  - Regaining continence after radical prostatectomy.
AB  - In this article, the author examines incontinence following radical prostatectomy
      and describes how nurses can provide advice, support and care for these patients.

PMID- 14649162
TI  - Faecal incontinence in adults.
AB  - Faecal incontinence is a distressing condition, which adversely affects the
      quality of life of adults of all ages. It is often preventable and easily
      treatable once a diagnosis has been made. Nurses should provide support and
      information for patients and their families and ensure they understand the causes
      of faecal incontinence and the treatment regimens available.

PMID- 14649163
TI  - Improving rehabilitation of severely obese patients.
AB  - Clinically severe obesity is a chronic condition affecting an increasing patient
      population. Attitudes, interventions, and equipment must be assessed and enhanced
      to provide the best possible care for these patients. However, basic principles
      of rehabilitation are effective in improving health and independence in
      individuals with this chronic medical condition. Such care can be provided in a
      manner that ensures safety for staff and patients.

PMID- 14649164
TI  - The journey of a lifetime: one nurse's experience in home health care.

PMID- 14649165
TI  - The experience of parenting an adolescent with spina bifida.
AB  - Parents of adolescents with spina bifida (SB) face unique challenges of which
      they may not be aware. The purpose of this study was to heighten awareness of the
      challenge of parenting such adolescents. This enhanced understanding can help
      rehabilitation professionals optimize their interventions with families. In this
      qualitative study, which was part of a larger mixed-method descriptive
      investigation exploring adaptation by adolescents with SB, we used content
      analysis to evaluate 20 parent interviews for common domain, themes, and
      subthemes. The analysis yielded four major domains: (a) daily life experiences,
      (b) the dance of individuation, (c) reflections on parenting, and (d) practice
      suggestions for healthcare professionals. Overall, experiences of the parents
      were positive. Parents described meeting daily demands and balancing independence
      dependence needs with the adolescent as major challenges. Rehabilitation
      professionals must provide guidance to foster autonomy, decision making,
      cognitive skill building, and coping skills to help parents and adolescents
      manage independence-dependence issues and multiple life demands.

PMID- 14649166
TI  - Nursing time and work in an acute rehabilitation setting.
AB  - Nursing staffing has long been recognized as a significant variable in a hospital
      budget even through the era of increased productivity and efficiency. In
      addition, patient acuity has been rising, and increasing demands on nursing
      personnel have been documented. These increased demands have affected nurse
      staffing, patient outcomes, and nurse retention, all of which have an impact on
      our healthcare system. Therefore, it is imperative that nursing time and work be
      examined in the acute rehabilitation setting--a setting in which research has
      been sparse. To estimate patient acuity, the activities of nursing personnel must
      be examined to establish timeframes for the care needed by patients. Previous
      studies have examined time and work according to pre-established patient acuity
      categories. California has passed legislation that requires mandatory nurse
      staffing ratios in response to the concerns about the adequacy of patient care
      and safety. We did this study to assess the time and work related to patients
      with different diagnoses that are typically found in a rehabilitation unit. The
      data collected can be used to develop a patient acuity system. This study sought
      to identify how nurses spend their time so that hidden costs and important
      interventions can be addressed by an institution's administration.

PMID- 14649167
TI  - Evaluating the effects of music on dyspnea during exercise in individuals with
      chronic obstructive pulmonary disease: a pilot study.
AB  - In this study, we examined the effects of music on the dyspnea and anxiety
      experienced by people with chronic obstructive pulmonary disease (COPD) when they
      are walking. A crossover design was used. Patients walked for 10 minutes without
      music and for 10 minutes while listening to music. The order of the interventions
      was determined by chance. The levels of perceived dyspnea (modified Borg scale)
      and anxiety (State-Trait Anxiety Inventory-State) were measured at baseline
      (before a 6-minute walk), at pretest (after that walk and before the 10-minute
      walks), and after the walks. Thirty subjects with a mean age of 70 +/- 7 years
      participated in the study. There were no differences in dyspnea or anxiety levels
      between the walks with music and with no music (p > 0.05). Despite some positive
      trends, this study did not provide conclusive evidence to support the efficacy of
      listening to music during exercise; further research is needed to support this
      intervention.

PMID- 14649168
TI  - Use of self-efficacy and dyspnea perceptions to predict functional performance in
      people with COPD.
AB  - This correlational and comparative study explored whether self-reports of self
      efficacy and dyspnea perceptions predict the perceived level of functional
      performance in adults who have chronic obstructive pulmonary disease (COPD). The
      convenience sample included 97 Caucasian men (52) and women (45). Participants
      had to have a forced expiratory volume in 1 second (FEV1) of less than 70%
      predicted, and a FEV1/forced vital capacity (FVC) of less than 70%. Participants
      were recruited from pulmonary function laboratories and from better breather
      support groups in a Midwestern state. Three standardized, self-report
      instruments, COPD Self-Efficacy Scale (CSES), the Pulmonary Functional Status and
      Dyspnea Questionnaire (PFSDQ), and Functional Performance Inventory (FPI) were
      used to measure the participants' self-report of their perceptions of self
      efficacy, dyspnea, and functional performance. Dyspnea predicted 38.1% of the
      variance in functional performance, with self-efficacy contributing an additional
      6.5% to the variance in the total sample. Self-efficacy predicted 36.5% of the
      variance in functional performance in men, with dyspnea contributing an
      additional 7.2% to the variance. However, in women, only dyspnea was a
      significant predictor of functional performance, at 48.5% when both dyspnea and
      self-efficacy were entered as independent variables. To improve patients'
      perceptions of functional performance, nurses can use methods such as breathing
      techniques and upper- and lower-body exercises that increase optimal management
      of dyspnea. Nurses may increase the self-efficacy of managing dyspnea by helping
      patients master breathing techniques and exercise through coaching and providing
      vicarious experiences through patient support groups or pulmonary rehabilitation
      programs.

PMID- 14649169
TI  - Just another day in the office.

PMID- 14649170
TI  - Sky's the limit. Interview by Tom Keighley.

PMID- 14649171
TI  - The trials and tribulations of independent consultancy. Going solo.

PMID- 14649172
TI  - Implementing new clinical guidelines: the manager as agent of change.
AB  - THIS ARTICLE aims to demonstrate how an increased knowledge of management issues
      can help improve health care. It focuses on change management, specifically the
      manager's role in implementing new clinical guidelines on sedation in a
      paediatric intensive care unit (PICU) setting. An action plan sets out the key
      stages of the change management process involved in implementing new guidelines
      (Box 1). There follows a critical analysis of the managerial issues involved in
      this action plan with a focus on the manager as a change agent.

PMID- 14649173
TI  - Workforce transformation: building firm foundations.

PMID- 14649174
TI  - More nurses: a proposal.
AB  - This paper recognises the complexities of the current political, professional and
      economic agendas. Its chief concern is to maintain the quality of student
      learning while ensuring the development of competent practitioners and as such,
      while accepting the government and professional strategies, we suggest that
      students should exit the programme after less than three years if they achieve
      competency. In the words of former RCN assistant director of nurse education
      Sally Thomson (Alderman and Knight 1999): 'Quality is a better measure than
      quantity.' The profession has chosen to go down a competency based route; the
      amount of time taken, therefore, should become less significant. The approach
      suggested by the authors would maximise the number of students achieving
      registration without compromising standards or intensifying the existing
      stressors of registered staff. It should also ease the financial burden on many
      students and save public money, such as the 24 weeks of bursary for each student,
      and should increase the number of graduates as students are helped financially to
      complete the programme's degree component. Failure to consider this proposal
      seriously, we believe, might result in more students, less supervision, poorer
      quality placements, worse learning and less competence.

PMID- 14649175
TI  - Understanding people.

PMID- 14649176
TI  - A nurse--envisaged NHS.

PMID- 14649177
TI  - 'Nurses have so much to offer'. Interview by David Crouch.

PMID- 14649178
TI  - Raising awareness of the rise in allergy-related conditions.
AB  - The incidence of allergic disease is increasing, with one in three people now
      reported as having some kind of allergy. Allergy support groups are working to
      raise awareness of this increase and also to highlight the inadequacies in NHS
      allergy management services. This has implications for nursing practice, as
      nurses are involved in identification and documentation of patients' allergies as
      well as in the management of allergic reactions including anaphylaxis.

PMID- 14649179
TI  - Non-surgical management options for menorrhagia.
AB  - Menorrhagia is a common problem in women and increasing numbers are seeking help
      and advice regarding management. In many cases, surgery is not appropriate and so
      awareness of alternative treatments is important. The aim of this review is to
      summarise the evidence available regarding current medical therapies.

PMID- 14649180
TI  - What you need to know about ... sexually acquired reactive arthritis.

PMID- 14649181
TI  - Training and support to enable home immunoglobulin therapy.
AB  - This article describes the development of an immunoglobulin home therapy and
      support service. The service provides patients with the education and training
      that they need to be able to undertake immunoglobulin therapy at home. To
      facilitate this the trust's competency-based enhanced practice framework was
      adapted. Evaluation through clinical audit and a patient satisfaction survey has
      yielded positive results, indicating that the enhanced practice framework
      provides a robust and effective approach to patient education.

PMID- 14649182
TI  - Monitoring critically ill patients in accident and emergency.
AB  - Nurses play a vital role in A&E, monitoring patients' physiological responses to
      stress and disease, and identifying any deterioration in their condition so that
      appropriate treatment can be instigated. This article describes the monitoring
      techniques used in A&E to assess critically ill patients.

PMID- 14649183
TI  - 'It's about having a vision and providing leadership'. Interview by Alison Whyte.

PMID- 14649184
TI  - Making a difference in chronic pain management.

PMID- 14649185
TI  - At your assistance.

PMID- 14649186
TI  - Right up to the end.

PMID- 14649187
TI  - Tired of waiting. Interview by Lucy Gooding.

PMID- 14649188
TI  - Stairway to the top. Interview by Charlotte Alderman.

PMID- 14649189
TI  - Living on borrowed time.

PMID- 14649190
TI  - Worried sick.

PMID- 14649191
TI  - A fresh perspective on health.

PMID- 14649192
TI  - Critical companionship: Part 1.
AB  - This article is the first of two presenting critical companionship as a metaphor
      and framework for learning from healthcare experiences. Critical companionship is
      a helping relationship in which an experienced facilitator (often, but not
      necessarily, a colleague) accompanies another on an experiential learning
      journey, using methods of 'high challenge' and 'high support' in a trusting
      relationship. The overall purpose of critical companionship is to enable others
      to practise in ways that are person centred and evidence based. Critical
      companionship is effective in a variety of one-to-one or group learning contexts,
      such as practice development projects, organisational change, practitioner
      research, work-based learning, clinical supervision and action learning. In this
      article, the development and testing of the critical companionship framework,
      through action research, are briefly described. The framework is then presented
      and illustrated with exemplars of critical-companionship expertise in an acute
      medical ward. Part 2 highlights how the framework was used in a practice
      development programme with NHS trusts for older people's services, to help nurses
      to become critical companions.

PMID- 14649193
TI  - Using clinical governance to standardise an epidural service.
AB  - Continual epidural infusions are an accepted intervention for the management of
      postoperative pain (McQuay and Moore 1998). Benchmarking nationally through an
      unpublished audit of Pain Society members identified variation in the
      concentrations prescribed and delivery systems used. These differences were
      reflected in local practice. As a result of the local disparity in the management
      and provision of epidural infusions, the acute pain service at Southampton
      University Hospitals NHS Trust worked in conjunction with the pharmacy department
      to standardise the service provided to patients and staff. This process was
      complicated by the difficulty in obtaining anaesthetist consensus for a standard
      solution that was commercially available and funding for the dedicated delivery
      system.

PMID- 14649195
TI  - Nanny state.

PMID- 14649194
TI  - Suctioning techniques for the removal of respiratory secretions.
AB  - Suctioning techniques are a necessary nursing intervention to remove respiratory
      secretions and maintain optimum ventilation and oxygenation in patients who are
      unable to get rid of these secretions independently. This intervention can induce
      problems and it is important that the correct procedure is adhered to so that
      patient safety and comfort are maintained. Nurses should be competent in
      assessing the need for suction. The decision to perform this procedure should be
      based on the patient's clinical signs and symptoms and should not be undertaken
      as a matter of routine.

PMID- 14649196
TI  - [Effects of additives on tissue culture and rapid propagation of Dendrobium
      canducum].
AB  - Effects of additives on tissue culture and rapid propagation of Dendrobium
      canducum Walla. ex Lindal. by 1/2 MS added activated charcoal, plant growth
      regulators, banana juice, apple juice and potato juice were studied. The result
      showed that the medium 1/2 MS + 0.1 mg/L NAA + 0.5% activated charcoal was
      suitable for propagation of protocorm-like body (PLB), the medium 1/2 MS + 0.5
      mg/L 6-BA + 0.5% activated charcoal was suitable for differentiation of PLB, and
      0.5% activated charcoal, banana juice and apple juice could promote root
      formation and growth.

PMID- 14649197
TI  - [Success and problems on introduction of Scaphium lychnophorum at Xishuangbanna].
AB  - In 1970's some Scaphium lychnophorum seedlings were introduced from Kampuchea to
      Xishuangbanna, Yunnan Province. These seedlings have grown into the large trees
      and bore fruits to propagate successfully in the nature over many years. Some
      problems of the plant adaptability and phenological reaction to the local
      environment, as well as the main cultivable measures were summarized in this
      paper.

PMID- 14649198
TI  - [The study on fingerprint of compound ginseng injection by powder X-ray
      diffraction].
AB  - OBJECTIVE: To establish the fingerprint of "Compound Ginseng Injection",
      including Ginseng and Pericarpium Citri Reticulatae (Chenpi) raw material, their
      intermediate and injection by powder X-ray diffraction. METHOD: Powder X-ray
      diffraction was used to analyze Ginseng and Chenpi raw material, their
      intermediate and injection, contrasted and analyzed the graphs to establish the
      fingerprint. RESULT: The fingerprint of Ginseng and Chenpi raw material, their
      intermediate and injection was established. Furthermore, the fingerprint of them
      showed an excellent recurrence and stability. CONCLUSION: Powder X-ray
      diffraction method can be used to control the quality of "Compound Ginseng
      Injection".

PMID- 14649199
TI  - [Isolation and HPLC analysis of ginkgolic acid].
AB  - OBJECTIVE: To isolate ginkgolic acids (GA) from exopleura of Ginkgo biloba and to
      analyse GA. METHODS: GA were ultrasonic-extracted from exopleura of Ginkgo biloba
      with petroleum ether, and purified by silica gel column chromatography. The
      content of GA in sample was determined by HPLC with methanol-3% acetic acid
      (90:10) as mobile phase at a flow rate of 1 ml/min. UV detection wavelength was
      set at 310 nm. A HiQ sil C18 column was used at 40 degrees C in analysis.
      RESULTS: A good linearity was obtained in the range of 1.144-5.720 micrograms (r
      = 0.9978) for GA. The average recovery of GA was 97.50% with RSD of 1.70%.
      CONCLUSION: The method may be employed to prepare GA from exopleura of Ginkgo
      biloba. The analysis method for GA is accurate and reliable, and can be used for
      determination of GA in sample.

PMID- 14649200
TI  - [Studies on chemical constituents from Phyllostachys pubescens].
AB  - OBJECTIVE: To study the chemical constituents from Phyllostachys pubescens.
      METHODS: A extract of P. pubescens was prepared by decocting with boiling water,
      chromatographed on macroporus resin column and eluted by ethanol. The eluant was
      separated on silica gel column by eluting with various proportions of chloroform
      methanol-water. UV, MS, 1H NMR and 13C NMR were used to elucidate these chemical
      constituents structure. RESULT: Two compounds were isolated as vitexin (I) and
      orientin (II). CONCLUSION: Two compounds were isolated from this genus for the
      first time.

PMID- 14649201
TI  - [Study on invasion and metastasis related factors in differentiation of SMMC-7721
      cells induced by matrine].
AB  - OBJECTIVE: To study the inhibition effect on invasion and metastasis related
      factors in differentiation of SMMC-7721 cells induced by matrine. METHOD: Human
      hepatoma cell lines SMMC-7721 were cultured in vitro and treated by 0.5 g/L, 0.8
      g/L, 1.0 g/L matrine. Then the cell growth curve was protracted, the cell form
      was observed by light microscope, the invasion and metastasis related factors
      were measured with cell adhesion test, cell migration test and cell invasion
      test. The data was collected and analyzed with statistical methods to evaluate
      roundly the inducing differentiation function of matrine. RESULT: Treated by 0.8
      g/L, 1.0 g/L matrine, the proliferation of SMMC-7721 was inhibited markedly, and
      the malignant cell form tended to normal differentiation. It was also found that
      matrine could inhibit cell invasion and metastasis related factors, including
      adhesive ability to FN, migrative ability through the polycarbonate filter, and
      invasive ability through matrigel. CONCLUSION: Matrine is a good differentiation
      inducer, it can not only inhibit the cell proliferation and induce the cell form
      differentiation, but also significantly inhibit the invasion and metastasis
      ability of SMMC-7721 through several steps, involved cell adhesion, migration and
      invasion.

PMID- 14649202
TI  - [Biochemical pharmacological effects of lurongjing on young or old mice].
AB  - OBJECTIVE: To investigate the effect of Lurongjing (LRJ) on young or old mice.
      METHODS: In vivo monoamine oxidase (MAO) and superoxide dismutase(SOD)
      activities, the contents of monoamines(5-HT, NE, DA), malondialdehyde (MDA), RNA
      and protein, and the incorporations of [3H] Uridine into RNA and [3H] Leucine
      into protein in liver tissue were measured. RESULTS: The inhibition of MAO-B
      activity and the increase of monoamines(5-HT, DA) level, the increase of RNA and
      protein level, and the incorporations of [3H] Uridine into RNA and [3H] Leucine
      into protein in liver tissue, the enhancement of SOD activity and the decrease of
      MDA content in brain and liver tissues were selectively observed in old mice(24
      months) than in young mice(1 month) by LRJ (i.g., 4.0 g/kg) administrated orally
      for 10 successive days. CONCLUSION: LRJ exhibits some anti-aging effect in old
      mice.

PMID- 14649203
TI  - [The study on the effects of the oil from Hippophae rhamnoides in hematopoiesis].
AB  - OBJECTIVE: To investigate the possibility of the oil from Hippophae rhamnoides
      (OHR) in supporting the hematopoitic reconstitution after high dose chemotherapy.
      METHOD: The mice were fed with OHR and variation of blood cell counts of the mice
      was recorded. Animal models of myelosuppression were built by 5-Fu intra
      peritoneal infusion. The effects of OHR in the hematopoietic reconstitution were
      observed. RESULTS: The counts of erythrocytes of OHR group were significantly
      elevated. The blood cell counts in myelosuppression mice fed with OHR exceeded
      those in control group, and the mortality was decreased. CONCLUSION: OHR can
      improve the hematopoiesis of erythroid linage. Like G-CSF, OHR can stimulate the
      recovery of hematopoiesis after chemotherapy.

PMID- 14649204
TI  - [Effects of ursolic acid on liver-protection and bile secretion].
AB  - OBJECTIVE: To study the liver-protection and promoting bile secretion of ursolic
      acid. METHODS: Ursolic acid was administrated to the mice with liver injury
      induced by CCl4 or APIT. ALT, AST levels in serum were examined. The bile flow
      rate and the concentration of the main components in the bile of rats
      administrated with ursolic acid were estimated. RESULTS: Ursolic acid could
      decrease the serum ALT, AST, SB levels in the mice treated with CCl4 or APIT,
      promote the secretion of bile and increase the concentration of bilirubin in the
      bile. CONCLUSION: Ursolic acid exhibited significant liver protection and
      promoting blie secretion.

PMID- 14649205
TI  - [Study on supercritical CO2 extracting conditions on Phyllanthus urinaria].
AB  - The technology for extracting Phyllanthus urinaria L. with supercritical CO2 as a
      solvent was described. The effect of extraction pressure, extraction temperature,
      extraction time and 85% ethanol-H2O co-solvent capacity have been studied. The
      proper technology requirements were determined through orthogonal experiment and
      the result shows the rate of extraction can be up to 9.0 percent, after
      extracting for 2.5 hours under the condition of extraction pressure 18 MPa,
      extraction temperature 50 degrees C, separation temperature 42 degrees C,
      separation pressure 5.8 +/- 0.2 MPa and CO2 flux 3.0 +/- 0.2 L/h.

PMID- 14649207
TI  - Novel regulation of insulin secretion: the role of mitochondria.
AB  - Coupling of glucose entry to insulin secretion in pancreatic beta-cells depends
      on numerous intracellular metabolic steps. In this process, mitochondria play a
      central role, and defects in this organelle are associated with impaired glucose
      evoked insulin release. In response to a glucose rise, nucleotides and
      metabolites are generated by mitochondria and participate, together with
      cytosolic Ca2+, in the stimulation of insulin exocytosis. This review describes
      the mitochondria-dependent pathways of regulated insulin secretion. In addition,
      new potential drug targets for therapeutic interventions in diabetes are
      discussed.

PMID- 14649206
TI  - [Effect of ligustrazine on proliferative glomerulonephritis].
AB  - OBJECTIVE: To investigate the therapeutic effect of ligustrazine on proliferative
      nephritis. METHODS: 45 patients with mesangial cell proliferation were randomly
      divided into two groups according to age, clinical manifestations and the
      pathological lesions. Steroid, cyclophosphamide, losartan and dipyridamole were
      given to 20 patients in the control group. Ligustrazine with the dosage of 80 mg
      twice a day was given to 25 patients in the treatment group by intravenous
      perfusion besides the medicine used in the control group. The course of
      ligustrazine treatment lasted three weeks. RESULT: The proteinuria and hematuria
      were decreased significantly with the increases of urine volume, serum albumin
      and creatinine clearance after ligustrazine treatment. The improvement of serum
      albumin, proteinuria and hematuria in the treated group were significant compared
      with control group after treatment. CONCLUSION: Ligustrazine is eutherapeutic in
      treating proliferative glomerulonephritis, with the less risk of hemorrhage,
      ligustrazine can be used for long-term treatment without special monitored.

PMID- 14649208
TI  - Unmet medical needs and therapeutic goals in the treatment of type 2 diabetes.
AB  - One of the main goals in the treatment of type 2 diabetes mellitus is to produce
      near-normal glucose levels to prevent the development of diabetic complications.
      Available treatments do not succeed in restoring normoglycemia in the long term.
      The recently improved knowledge of key pathogenic mechanisms of type 2 diabetes
      has led to a multitude of new molecular targets. The main goal is the maintenance
      of beta-cell function, as its decline is the major reason for impairment in
      glucose tolerance over time. Other tissues or systems may also be interesting
      targets. No single drug is likely to reverse all aspects of the disease, but the
      main aim is to provide more effective, better tolerated and better patient
      tailored combinations.

PMID- 14649209
TI  - Protein tyrosine phosphatase 1B inhibitors for the treatment of type 2 diabetes
      and obesity: recent advances.
AB  - This review outlines the physiology of protein tyrosine phosphatase 1B (PTP1B)
      and its potential involvement in the states of insulin resistance that
      characterizes both obesity and type 2 diabetes. The primary focus of this review
      is upon the elucidation of the role and control of PTP1B enzyme activity in
      obesity and type 2 diabetes. Furthermore, since selectivity and cell permeability
      are the two most important requirements for the development of successful PTP1B
      inhibitors, recent progress in finding compounds meeting these criteria are
      discussed.

PMID- 14649210
TI  - H3 receptor antagonists/inverse agonists as anti-obesity agents.
AB  - The role of histamine in a variety of central nervous system functions is
      emerging as increasingly complex, with known effects on behavioral and
      homeostatic functions. With the discovery of presynaptic H3 receptors and the
      identification of novel ligands for these sites, new pharmacological data suggest
      a potential role for H3 antagonists and/or inverse agonists in the control of
      feeding, appetite and body weight. The in vitro and in vivo attributes of these
      compounds support the prospect that one of the new lead agents currently under
      preclinical investigation will have the properties required for clinical utility
      as an anti-obesity agent.

PMID- 14649211
TI  - Neuropeptide Y Y5 receptor antagonists as anti-obesity drugs.
AB  - Neuropeptide Y (NPY) is present in the hypothalamus, where it is believed to play
      a key role in the control of food intake. Evidence for this assertion has come
      from studies demonstrating that acute administration of NPY into the hypothalamus
      or into the brain ventricles leads to increased food intake. In the case of
      chronic administration, the hyperphagic effects of NPY are prolonged, leading to
      the development of an obese state. NPY levels in the hypothalamus are temporally
      correlated with food intake and are markedly elevated in response to energy
      depletion. However, attempts to demonstrate an important role for NPY in the
      control of food intake using NPY knockout mice, NPY antisense
      oligodeoxynucleotides and anti-NPY antibodies has produced equivocal results.
      Despite this, many pharmaceutical companies have moved ahead with the search for
      antagonists of NPY receptor subtypes as appetite suppressant/anti-obesity agents.
      Antagonists of the NPY Y5 subtype seemed initially promising since analogs of NPY
      with high selectivity for this receptor strongly stimulated food intake. However,
      once again, attempts to inhibit the signaling of NPY through the NPY Y5 receptor
      produced equivocal effects on food intake. Many thousands of NPY Y5 antagonists
      have been made which fall into two main categories: those that influence food
      intake and those that do not. Those compounds that do inhibit food intake appear
      to do so by interactions with non-NPY Y5 related mechanisms. Thus, current
      evidence would suggest that antagonists of NPY acting through the NPY Y5 receptor
      subtype will not be useful appetite suppressant/anti-obesity agents.

PMID- 14649212
TI  - Therapeutic uses of dehydroepiandrosterone.
AB  - Over recent years, increased attention has been paid to the possibility that
      dehydroepiandrosterone (DHEA) may have therapeutic benefits. Several clinical
      trials of DHEA have been conducted, investigating the use of this steroid in the
      treatment of conditions ranging from chronic inflammatory disease to psychiatric
      disorders. Possible replacement therapy with DHEA in adrenal insufficiency and in
      old age has also been investigated. This review evaluates our current
      understanding of the possible therapeutic value of DHEA. Evidence of beneficial
      effects is discussed and areas where further research is needed are highlighted.
      Possible adverse effects of long-term DHEA therapy are also considered.

PMID- 14649213
TI  - Use of estrogen antagonists and aromatase inhibitors in endometriosis.
AB  - Endometriosis is an estrogen-dependent disorder mostly occurring in reproductive
      age women. Various therapies have been used in an attempt to treat endometriosis,
      including ovarian suppression therapy, surgical treatment or a combination of
      these strategies. However, in general, substantial surgery remains the primary
      treatment option for endometriosis at all stages. Recently, aromatase inhibitors
      and anti-estrogens have been proposed as novel potential candidates. The
      rationale for the use of aromatase inhibitors is mostly related to the high
      aromatase expression in endometriotic cysts and extra-ovarian endometriotic
      implants. Among anti-estrogens, raloxifene has been investigated in animal models
      with good results, but in premenopausal women, the compound does not seem to
      suppress estrogen production.

PMID- 14649214
TI  - Delivery of testosterone replacement therapy.
AB  - Optimal testosterone replacement therapy remains a considerable challenge for the
      estimated five out of 1000 men in the general community with androgen deficiency.
      Oral delivery is not possible due to rapid first pass metabolism and short half
      life. Testosterone derivatives have been developed to enhance intrinsic
      androgenic potency, prolong duration of action, or improve oral bioavailability
      of synthetic androgens. Structural modification of testosterone include 17 beta
      esterification, 17 alpha-alkylation, 1-methylation, addition of a 19-normethyl
      group, and 7 alpha-methylation. Currently, oral (testosterone undecanoate),
      transcutaneous (Andropatch, Virormone, Testoderm (ALZA Corp), Testogel),
      sublingual (testosterone cyclodextrin), intramuscular (Sustanon, Primoteston
      Depot), and fused crystalline testosterone pellet preparations are available for
      clinical use. Transbuccal testosterone systems have also been developed for
      clinical use and require twice daily application. Suspensions of biodegradable
      microspheres consisting of a polyglycolide-lactide matrix laden with testosterone
      can deliver stable, physiological levels of testosterone for 2 to 3 months.
      Micronized testosterone has low oral bioavailability requiring high daily doses.
      7 alpha-Methyl 19-nortestosterone, a potent, synthetic androgen free of
      hepatotoxicity, has tissue-specific selectivity, being susceptible to
      aromatization but not 5 alpha-reduction, thereby potentially avoiding
      intraprostatic androgen amplification.

PMID- 14649216
TI  - Fidarestat. Sanwa Kagaku/NC Curex/Sankyo.
AB  - Fidarestat is an aldose reductase inhibitor being co-developed by Sanwa Kagaku,
      NC Curex (a joint venture company created by Japan Energy and Kaken) and Sankyo,
      for the potential treatment of diabetic neuropathy.

PMID- 14649215
TI  - Controversy of hormone treatment and cardiovascular function: need for
      strengthened collaborations between preclinical and clinical scientists.
AB  - Over the last five years, there have been several major randomized clinical
      trials assessing the use of hormone therapy as an adjunct treatment for primary
      and secondary prevention of cardiovascular disease. Results of these trials have
      called into question existing dogma from epidemiological and basic science
      studies that estrogen provides protection against development of cardiovascular
      disease. When studies are evaluated for design, type and duration of hormone
      treatment, and outcomes, directions for future research become apparent. Improved
      hormone formulations and selective estrogen receptor modulators that help to
      maintain vascular function and limit progression of cardiovascular occlusive
      disease need to be developed. This will depend upon improved understanding of:
      (i) the distribution and regulation of estrogen receptors in vascular tissue,
      (ii) genomic interactions of estrogens and progestins, (iii) association of the
      estrogen receptor and other genetic polymorphisms with particular vascular
      functions, and (iv) better definition of timing and dosing for therapeutic
      intervention. The mechanisms of interactions between coagulation proteins,
      inflammatory cytokines, platelets and the vessel wall should be defined so that
      the thrombotic risk for an individual woman can be identified and reduced, and
      progression of chronic disease processes associated with loss of ovarian hormones
      can be slowed.

PMID- 14649217
TI  - Insulin glulisine. Aventis Pharma.
AB  - Aventis Pharma (formerly Hoechst Marion Roussel) is developing insulin glulisine,
      a fast-acting insulin analog, for the potential treatment of hyperglycemia in
      both type 1 and 2 diabetes. Aventis has submitted an NDA and an MAA to the FDA
      and the EMEA, respectively.

PMID- 14649218
TI  - CJC-1131. ConjuChem.
AB  - ConjuChem is developing CJC-1131, a drug affinity complex conjugate of glucagon
      like peptide 1 for the potential treatment of type 2 diabetes. In August 2003, a
      phase I/II trial was completed and a phase II trial was expected to begin in
      October.

PMID- 14649219
TI  - [Basic study on cataract in China: current status and strategy].

PMID- 14649220
TI  - [The characteristic of clinical review].

PMID- 14649221
TI  - Retraction. Abstract 1785.

PMID- 14649222
TI  - [Ventilation in special situations. Mechanical ventilation in bronchiolitis].
AB  - Bronchiolitis is a prevalent viral disease in infants. Many of these infants
      require hospital admission and mechanical ventilation due to respiratory failure
      or apnea. The clinical and pathophysiological spectrum of this disease can range
      from two extremes, obstructive and restrictive disease, on which the indication
      for mechanical ventilation and the modality used should be based. Non-invasive
      ventilation is especially indicated in both obstructive and hypoxemic restrictive
      patterns and a pressure-controlled modality is recommended. In obstructive
      patterns, air trapping must be monitored, while in restrictive patterns the
      addition of positive end-expiratory pressure (PEEP) is indicated. High-frequency
      oscillatory ventilation is indicated in restrictive patterns with sever hypoxemia
      despite conventional ventilatory support or in cases of significant air leak
      syndromes. In all cases, a permissive hypercapnia strategy is recommended to
      prevent barotrauma. Sedation and muscle relaxation should be considered to
      facilitate adaptation to the ventilator and to try to limit the risks of air
      trapping, air leak, and barotrauma.

PMID- 14649223
TI  - [Ventilation in special situations. Mechanical ventilation in acute respiratory
      distress syndrome/acute pulmonary lesion].
AB  - Acute respiratory distress syndrome (ARDS), which was first described by Ashbaugh
      in 1967, consists of acute hypoxemic respiratory failure (PaO2/FiO2< or =200)
      associated with bilateral infiltrates on the chest radiograph caused by
      noncardiac diffuse pulmonary edema. Although ARDS is of multiple etiology,
      pulmonary or extrapulmonary injury can produce systemic inflammatory response
      that perpetuates lung disturbances once the initial cause has been eliminated.
      Most patients with ARDS require mechanical ventilation. Currently, the old
      standard is conventional ventilation optimized to protect against ventilator
      associated lung injury. Other mechanical ventilation strategies such as high
      frequency oscillatory ventilation, which is also based on alveolar recruitment
      and adequate lung volume, can be useful alternatives. In this review, the level
      of evidence for other therapies, such as prone positioning, nitric oxide and
      prostacyclin inhalation, exogenous surfactant, and extracorporeal vital support
      techniques are also analyzed.

PMID- 14649224
TI  - [Ventilation in special situations. Mechanical ventilation in congenital
      cardiopathies and pulmonary hypertension].
AB  - The cardiovascular and respiratory systems act as a functional unit. Mechanical
      ventilation modifies pulmonary volumes, which generates changes in autonomic
      nervous system reactivity and provokes tachy- or brady-cardia (depending on the
      tidal volume used). Mechanical ventilation also decreases cardiac filling volumes
      (pre-load) and alters pulmonary vascular resistances. In addition, intrathoracic
      pressures are enlarged, which usually produces a decrease in right atrium filling
      and an increase in right ventricle afterload. If coronary flow is impaired,
      myocardial contractility is reduced. However, if cardiac failure is present,
      mechanical ventilation is especially beneficial because it corrects hypoxia and
      respiratory acidosis, decreases the work of breathing, and improves stroke
      volume. Mechanical ventilation in congenital heart diseases is indicated either
      as lifesaving support or as physiopathological treatment to modify the ratio
      between pulmonary and systemic flow. As a general rule, if excessive pulmonary
      blood flow is present, the aim of respiratory support is to increase pulmonary
      vascular resistance by using high levels of airway pressure and even by
      delivering FiO2<21%. When there is low pulmonary flow, the lowest possible
      intrathoracic pressures should be used, especially in cases of pulmonary
      hypertension, which will also require high FiO2. However, mechanical ventilation
      has adverse effects and consequently it must be stopped as early as possible,
      once the child is stable and requires minimal cardiopulmonary support. Weaning
      can even be performed in the operating room, when the surgical procedure is
      finished. When this is not possible, weaning should be performed in the pediatric
      intensive care unit. Because there are no criteria for successful withdrawal of
      mechanical support in congenital heart disease, general pediatric criteria should
      be used.

PMID- 14649225
TI  - [Ventilation in special situations. Neonatal mechanical ventilation].
AB  - Severe respiratory failure is a common problem in premature neonates. We review
      the various ventilation modes available in the neonatal intensive care unit, as
      well as their indications, settings, and complications.

PMID- 14649226
TI  - [Ventilation in special situations. Mechanical ventilation during transportation
      of pediatric patients].
AB  - Most severe pediatric injuries occur far from regional centres specialized in the
      definitive care of the critically-ill child. Adequate initial stabilization and
      an appropriate transport system significantly decrease morbidity and mortality in
      these patients. In the last few years, technological developments have improved
      the quality of medical transportation. Mechanical ventilation is one of the
      elements that has been affected by these advances with portable ventilators and
      monitoring systems that are increasingly similar to those used in pediatric
      intensive care units. To prevent complications from developing during
      transportation, adequate preparation is required consisting of (i) prior
      stabilization of the patient, (ii) assessment of potential risks and specific
      needs, (iii) monitoring, (iv) transport preparation, and (v) assessment of vital
      signs and patient management. Portable ventilators are designed to be used for
      short periods under difficult conditions (temperature changes, altitude, rain,
      knocks, etc.). Consequently they should have specific common characteristics:
      portability, resistance, ease of handling, low electricity and gas consumption,
      and safety. They should also be easy to set up. Their programming is generally
      similar to that of conventional ventilators and should be based on the
      physiologic characteristics of the child according to age and underlying process.

PMID- 14649227
TI  - [Clinic application of fiberbronchoscope in the therapy of central airway
      obstruction and construction].

PMID- 14649228
TI  - On: Repression, transference and reconstruction.

PMID- 14649229
TI  - [IgE regulation in asthma pathogenesis and development of a monoclonal anti-IgE
      antibody for the treatment of allergic asthma].

PMID- 14649230
TI  - Ambulatory community-acquired pneumonia: the predominance of atypical pathogens.

PMID- 14649231
TI  - Time for a new approach for reporting herbal medicine adverse events?

PMID- 14649232
TI  - Medicare beneficiaries don't receive available preventive services.

PMID- 14649233
TI  - Safety experts offer strategies for pediatric drug error prevention.

PMID- 14649234
TI  - Team approach helps to reduce blood pressure in African-American men.

PMID- 14649236
TI  - Nodding disease: mystery of southern Sudan.

PMID- 14649235
TI  - Cancer survival rates higher in privately insured.

PMID- 14649237
TI  - Neurologists say Florida woman is very unlikely to recover.

PMID- 14649238
TI  - Alpha-synuclein gene triplication discovered in Parkinson's disease.

PMID- 14649239
TI  - Prion probing comes up with the goods.

PMID- 14649240
TI  - Social rejection may be pain to the brain.

PMID- 14649241
TI  - Monkeys use brain power to manoeuvre a robotic arm.

PMID- 14649242
TI  - Gene for rare ataxia identified in mouse studies.

PMID- 14649243
TI  - Taking a shot at neuropathic pain.

PMID- 14649244
TI  - Hands: the last great smallpox outbreak in Minnesota (1924-25).

PMID- 14649245
TI  - Porcine cysticercosis in village pigs of North-West Cameroon.
AB  - A study was carried out in two villages and one marketplace of the Batibo sub
      division in North-West Cameroon to determine the prevalence of porcine
      cysticercosis. The results showed that 4.44% of 383 pigs were positive at tongue
      examination whereas ELISA detected circulating antigens in 27.7% of 271 pig sera.
      A questionnaire survey in 140 pig-raising households indicated that 59.3% of them
      lacked latrines while in 75.7% of the households members defecated directly into
      pigpens. The seroprevalence of porcine cysticercosis was significantly higher in
      households without latrines than in those with latrines. Similarly, significantly
      more seropositive pigs were present in households that defecated in the pig pens
      (35.5%) than in those that did not (14.4%). Although 91.4% of pig raising
      households did know of pig cysticercosis, only 28.6% were aware of the link with
      human taeniasis and only 10.7% were aware of human cysticercosis.

PMID- 14649246
TI  - Nonbeneficial research with individuals who cannot consent: is it ethically
      better to enroll healthy or affected individuals?

PMID- 14649247
TI  - "Exempt" research after the privacy rule.

PMID- 14649248
TI  - Women in early phase trials: an IRB's deliberations.

PMID- 14649249
TI  - Cultural issues in genetic research with American Indian and Alaskan Native
      people.

PMID- 14649250
TI  - The e-recruitment of participants for clinical trials.

PMID- 14649251
TI  - Kawasaki disease. Involution of giant coronary aneurysms after prolonged anti
      inflammatory treatment.

PMID- 14649252
TI  - The New Face of Space: selected proceedings of the 53rd International
      Astronautical Federation Congress, Houston, Texas, USA, 10 October - 19 October
      2002.

PMID- 14649253
TI  - Physiology, medicine, long-duration space flight and the NSBRI.
AB  - The hazards of long-duration space flight are real and unacceptable. In order for
      humans to participate effectively in long-duration orbital missions or continue
      the exploration of space, we must first secure the health of the astronaut and
      the success of such missions by assessing in detail the biomedical risks of space
      flight and developing countermeasures to these hazards. Acquiring the
      understanding necessary for building a sound foundation for countermeasure
      development requires an integrated approach to research in physiology and
      medicine and a level of cooperative action uncommon in the biomedical sciences.
      The research program of the National Space Biomedical Research Institute (NSBRI)
      was designed to accomplish just such an integrated research goal, ameliorating or
      eliminating the biomedical risks of long-duration space flight and enabling safe
      and productive exploration of space. The fruits of these labors are not limited
      to the space program. We can also use the gained understanding of the effects and
      mechanisms of the physiological changes engendered in space and the applied
      preventive and rehabilitative methods developed to combat these changes to the
      benefit of those on Earth who are facing similar physiological and psychological
      difficulties. This paper will discuss the innovative approach the NSBRI has taken
      to integrated research management and will present some of the successes of this
      approach.

PMID- 14649255
TI  - Women and couples in isolated extreme environments: applications for long
      duration missions.
AB  - Expedition teams provide a number of analogs relevant to crew selection for long
      duration space missions. Three groups were studied that varied in team
      composition. Group 1 was a two woman international dyad that traversed the
      Antarctic continent in 97 days. Similarities in problem solving approach, respect
      for each other's opinions, and a collaborative process of decision making were
      evident. Group 2 was composed of four women, all from different countries,
      engaged in a six week trek across Greenland. The most important factors in
      overcoming interpersonal difficulties and contributing to the successful
      completion of the expedition were mutual respect and motivation to maintain
      positive and supportive relationships. Group 3 consisted of three married couples
      from different countries icelocked on a boat in the High Arctic for a 9 month
      period. The emotional support of and ability to confide in their partner were
      extremely important in alleviating interpersonal tensions, and contributed to the
      generally effective functioning of the group. Women add an element of emotional
      support and help to other team members that is not as evident in all-male groups.
      Selection of couples with strong bonds to each other is another paradigm for crew
      selection for extended missions.

PMID- 14649254
TI  - Synthesis of biomass and utilization of plants wastes in a physical model of
      biological life-support system.
AB  - The paper considers problems of biosynthesis of higher plants' biomass and
      "biological incineration" of plant wastes in a working physical model of
      biological LSS. The plant wastes are "biologically incinerated" in a special
      heterotrophic block involving Californian worms, mushrooms and straw. The block
      processes plant wastes (straw, haulms) to produce soil-like substrate (SLS) on
      which plants (wheat, radish) are grown. Gas exchange in such a system consists of
      respiratory gas exchange of SLS and photosynthesis and respiration of plants.
      Specifics of gas exchange dynamics of high plants--SLS complex has been
      considered. Relationship between such a gas exchange and PAR irradiance and age
      of plants has been established. Nitrogen and iron were found to the first to
      limit plants' growth on SLS when process conditions are deranged. The SLS
      microflora has been found to have different kinds of ammonifying and denitrifying
      bacteria which is indicative of intensive transformation of nitrogen-containing
      compounds. The number of physiological groups of microorganisms in SLS was, on
      the whole, steady. As a result, organic substances--products of exchange of
      plants and microorganisms were not accumulated in the medium, but mineralized and
      assimilated by the biocenosis. Experiments showed that the developed model of a
      man-made ecosystem realized complete utilization of plant wastes and involved
      them into the intrasystem turnover.

PMID- 14649256
TI  - Some approaches to medical support for Martian expedition.
AB  - Medical support in a Martian expedition will be within the scope of crew
      responsibilities and maximally autonomous. Requirements to the system of
      diagnostics in this mission include considerable use of means and methods of
      visualization of the main physiological parameters, telemedicine, broad usage of
      biochemical analyses (including "dry" chemistry), computerized collection,
      measurement, analysis and storage of medical information. The countermeasure
      system will be based on objective methods of crew fitness and working ability
      evaluation, individual selection of training regimens, and intensive use of
      computer controlled training. Implementation of the above principles implies
      modernization and refinement of the countermeasures currently used by space crews
      of long-term missions (LTM), and increases of the assortment of active and
      passive training devices, among them a short-arm centrifuge. The system of
      medical care with the functions of prevention, clinical diagnostics and timely
      treatment will be autonomous, too. The general requirements to medical care
      during the future mission are the following: availability of conditions and means
      for autonomous urgent and special medical aid and treatment of the most possible
      states and diseases, "a hospital", and assignment to the crew of one or two
      doctors. To ensure independence of medical support and medical care in an
      expedition to Mars an automated expert system needs to be designed and
      constructed to control the medical situation as a whole.

PMID- 14649257
TI  - Ground and on-orbit command and data handling architectures for the Active Rack
      Isolation System microgravity flight experiment.
AB  - The Active Rack Isolation System [ARIS] International Space Station [ISS]
      Characterization Experiment, or ARIS-ICE for short, is a long duration
      microgravity characterization experiment aboard the ISS. The objective of the
      experiment is to fully characterize active microgravity performance of the first
      ARIS rack deployed on the ISS. Efficient ground and on-orbit command and data
      handling [C&DH] segments are the crux in achieving the challenging objectives of
      the mission. The objective of the paper is to provide an overview of the C&DH
      architectures developed for ARIS-ICE, with the view that these architectures may
      serve as a model for future ISS microgravity payloads. Both ground and on-orbit
      segments, and their interaction with corresponding ISS C&DH systems are
      presented. The heart of the on-orbit segment is the ARIS-ICE Payload On-orbit
      Processor, ARIS-ICE POP for short. The POP manages communication with the ISS
      C&DH system and other ISS subsystems and payloads, enables automation of
      test/data collection sequences, and provides a wide range of utilities such as
      efficient file downlinks/uplinks, data post-processing, data compression and data
      storage. The hardware and software architecture of the POP is presented and it is
      shown that the built-in functionality helps to dramatically streamline the
      efficiency of on-orbit operations. The ground segment has at its heart special
      ARIS-ICE Ground Support Equipment [GSE] software developed for the experiment.
      The software enables efficient command and file uplinks, and reconstruction and
      display of science telemetry packets. The GSE software architecture is discussed
      along with its interactions with ISS ground C&DH elements. A test sequence
      example is used to demonstrate the interplay between the ground and on-orbit
      segments.

PMID- 14649258
TI  - Physical sciences research plans for the International Space Station.
AB  - The restructuring of the research capabilities of the International Space Station
      has forced a reassessment of the Physical Sciences research plans and a re
      targeting of the major scientific thrusts. The combination of already selected
      peer-reviewed flight investigations with the initiation of new research and
      technology programs will allow the maximization of the ISS scientific and
      technological potential. Fundamental and applied research will use a combination
      of ISS-based facilities, ground-based activities, and other experimental
      platforms to address issues impacting fundamental knowledge, industrial and
      medical applications on Earth, and the technology required for human space
      exploration. The current flight investigation research plan shows a large number
      of principal investigators selected to use the remaining planned research
      facilities.

PMID- 14649259
TI  - The Interplanetary Internet: a communications infrastructure for Mars
      exploration.
AB  - A strategy is being developed whereby the current set of internationally
      standardized space data communications protocols can be incrementally evolved so
      that a first version of an operational "Interplanetary Internet" is feasible by
      the end of the decade. This paper describes its architectural concepts, discusses
      the current set of standard space data communications capabilities that exist to
      support Mars exploration and reviews proposed new developments. We also speculate
      that these current capabilities can grow to support future scenarios where human
      intelligence is widely distributed across the Solar System and day-to-day
      communications dialog between planets is routine.

PMID- 14649260
TI  - Innovations in mission architectures for exploration beyond low Earth orbit.
AB  - Through the application of advanced technologies and mission concepts,
      architectures for missions beyond Earth orbit have been dramatically simplified.
      These concepts enable a stepping stone approach to science driven; technology
      enabled human and robotic exploration. Numbers and masses of vehicles required
      are greatly reduced, yet the pursuit of a broader range of science objectives is
      enabled. The scope of human missions considered range from the assembly and
      maintenance of large aperture telescopes for emplacement at the Sun-Earth
      libration point L2, to human missions to asteroids, the moon and Mars. The
      vehicle designs are developed for proof of concept, to validate mission
      approaches and understand the value of new technologies. The stepping stone
      approach employs an incremental buildup of capabilities, which allows for future
      decision points on exploration objectives. It enables testing of technologies to
      achieve greater reliability and understanding of costs for the next steps in
      exploration.

PMID- 14649261
TI  - Automation and Robotics for Human Mars Exploration (AROMA).
AB  - Automation and Robotics (A&R) systems are a key technology for Mars exploration.
      All over the world initiatives in this field aim at developing new A&R systems
      and technologies for planetary surface exploration. From December 2000 to
      February 2002 Kayser-Threde GmbH, Munich, Germany lead a study called AROMA
      (Automation and Robotics for Human Mars Exploration) under ESA contract in order
      to define a reference architecture of A&R elements in support of a human Mars
      exploration program. One of the goals of this effort is to initiate new
      developments and to maintain the competitiveness of European industry within this
      field.

PMID- 14649262
TI  - The challenges and opportunities of a commercial human spaceflight mission to the
      ISS.
AB  - ESA astronauts' ISS flight opportunities are considered as a vital source to meet
      the utilisation, operation and political objectives that Europe has established
      for participating in the International Space Station programme. Recent internal
      ESA assessments have demonstrated that a rate of three flights per year for
      European Astronauts should be maintained as a minimum objective. The current
      flight rate is lower than this. In order to improve this situation, in the
      context of the activation of the ESA ISS Commercialisation programme, ESA is
      developing the conditions for the establishment of commercially based human
      spaceflights with the financial support of both ESA and the private sector or, in
      the future, only the latter. ESA is working in a Partnership with the space
      industry to facilitate the implementation of such projects and support customers
      with a range of end-to-end commercial services. The opportunities and challenges
      of a "commercial human spaceflight", involving a member of the European Astronaut
      Corps, or a privately employed flight participant, are discussed here.

PMID- 14649263
TI  - Research priorities and plans for the International Space Station-results of the
      'REMAP' Task Force.
AB  - Recent events in the International Space Station (ISS) Program have resulted in
      the necessity to re-examine the research priorities and research plans for future
      years. Due to both technical and fiscal resource constraints expected on the
      International Space Station, it is imperative that research priorities be
      carefully reviewed and clearly articulated. In consultation with OSTP and the
      Office of Management and budget (OMB), NASA's Office of Biological and Physical
      Research (OBPR) assembled an ad-hoc external advisory committee, the Biological
      and Physical Research Maximization and Prioritization (REMAP) Task Force. This
      paper describes the outcome of the Task Force and how it is being used to define
      a roadmap for near and long-term Biological and Physical Research objectives that
      supports NASA's Vision and Mission. Additionally, the paper discusses further
      prioritizations that were necessitated by budget and ISS resource constraints in
      order to maximize utilization of the International Space Station. Finally, a
      process has been developed to integrate the requirements for this prioritized
      research with other agency requirements to develop an integrated ISS assembly and
      utilization plan that maximizes scientific output.

PMID- 14649264
TI  - Spatial and temporal coherence of filtered thermal light.
AB  - When a filter is placed in front of a double slit illuminated by a primary source
      of finite extent, the theory of partial coherence predicts that in general the
      interference fringes do not acquire unit visibility even as the passband of the
      filter is made arbitrarily narrow. The effect of reducing the filter bandwidth is
      that the visibility of the fringes tends to the modulus of the spectral degree of
      coherence and that more interference fringes become visible. A systematic
      experimental verification of these theoretical predictions is lacking so far and
      is provided here from the use of a highly sensitive CCD camera.

PMID- 14649265
TI  - Wadsworth mount redux: paraboloidal versus spherical gratings.
AB  - Spherical and paraboloidal diffraction gratings are considered for use on an
      experiment involving a collection of satelliteborne spectrographs that will
      investigate astrophysical plasmas in the spectral region from approximately 100
      to 300 A. We shall use eight spectrographs: Wadsworth mounts in near-normal
      incidence with effective focal lengths of 3 m, each centered on a chosen
      wavelength in this spectral range. Ray tracings show that paraboloidal gratings
      used in the Wadsworth mount have a significant increase in resolution over
      spherical gratings of the same effective focal length, used in the same mounting,
      as long as the spectral ranges are small (approximately 10% of the central
      wavelength). This increase in resolution is due to the spatial extent of coma for
      a paraboloidal grating that is less than the circle of least confusion of
      spherical gratings.

PMID- 14649266
TI  - All-dielectric reflection gratings: a study of the physical mechanism for
      achieving high efficiency.
AB  - The physical mechanism for the all-dielectric reflection gratings to achieve high
      efficiency in the -1st-order Littrow mounting is studied. The all-dielectric
      gratings consist of two parts, a surface-relief grating and a highly reflecting
      dielectric stack. The surface-relief grating sits on top of the reflecting stack.
      A simple analytical expression for diffraction efficiency is obtained in terms of
      the S-matrix elements of the two parts. By analyzing the expression we show that
      the diffraction can be interpreted as the interference of a symmetric wave and an
      antisymmetric wave. The conditions for achieving high diffraction efficiency are
      also identified. The analytical results are illustrated by numerical
      computations.

PMID- 14649267
TI  - All-fiber spot-size transformer for efficient free-space optical interconnecting
      devices.
AB  - A new concatenated configuration of optical fibers is proposed to improve
      misalignment tolerance and working distance in a free-space optical
      interconnection. The structure is composed of three segments: a thermally
      expanded core fiber, a coreless silica fiber, and a claddingless graded-index
      fiber. A numerical analysis for the design of each fiber segment is performed
      completely, and the device characteristics are experimentally evaluated in terms
      of the tolerances for a 1-dB coupling-loss increment against longitudinal,
      transverse, and angular misalignments.

PMID- 14649268
TI  - Finite-element analysis of birefringence and dispersion properties in actual and
      idealized holey-fiber structures.
AB  - Using a full-vector finite-element method, we calculate birefringence and
      dispersion in index-guiding photonic crystal fibers, also called holey fibers.
      Through real-model simulations the polarization-dependent dispersion in actual
      fiber structures is numerically demonstrated, for the first time to our
      knowledge. Furthermore the transverse-electric-field vector distributions in the
      fabricated holey fibers are also clarified for the two linearly polarized
      fundamental modes.

PMID- 14649269
TI  - Digital and analog readout systems for fiber-optic strain sensors as applied to
      the monitoring of roller element bearing systems.
AB  - A rotating machinery test rig was instrumented with fiber Fabry-Perot
      interferometer strain sensors for condition monitoring of rolling element
      bearings. Strain variations produced by ball passes were observed and analyzed in
      the time and frequency domain. Wavelength division multiplexing was utilized to
      simultaneously monitor the sensors with analog and digital readout systems-
      analog for high bandwidth and digital for high dynamic range and the monitoring
      of multiple sensors. The effects of imbalance on the shaft, changes in rotational
      speed, effects on the rotor system, and detection of bearing defects were
      investigated. Frequency peaks observed in the bearing sensor spectra closely
      matched predicted values. Imbalance and rotational speed tests showed good
      agreement with expected trends, and bearing defects were successfully detected.

PMID- 14649270
TI  - Measurement of pressure and temperature sensitivities of a Bragg grating
      imprinted in a highly birefringent side-hole fiber.
AB  - The sensing characteristics of a Bragg grating imprinted in a specially developed
      highly birefringent side-hole fiber were investigated in detail. We showed that
      such a grating has almost identical sensitivities to temperature for both
      linearly polarized modes LP01(x) and LP01(y) (approximately 5.9 pm/K) and
      significantly different sensitivities to hydrostatic pressure (-1.93 pm/MPa for
      LP01(x) and +5.37 pm/MPa for LP01(y) mode). The sensitivity differences versus
      mode polarization are so high that this effect can be employed for simultaneous
      sensing of temperature and pressure by interrogation of the wavelength shifts at
      LP01(x) and LP01(y) modes. Applying interferometric methods, we also measured the
      sensitivity of the host side-hole fiber to temperature and hydrostatic pressure
      for each polarization mode. Our results show that there is good agreement between
      the normalized sensitivities of the host side-hole fiber and those of the grating
      for the same polarization modes.

PMID- 14649271
TI  - Noise-equivalent change in radiance for misalignment noise in a double-sided
      interferogram.
AB  - Engineers designing optical alignment servo systems for Michelson interferometers
      and Fourier-transform infrared spectrometers need to predict the amount of noise
      expected from the small and randomly varying amounts of misalignment that occur
      as the servo attempts to maintain alignment while taking data. A formula is
      derived for the noise-equivalent change in radiance due to this effect and the
      formula's accuracy is demonstrated by comparison of its predictions to the errors
      found in simulated interferometer measurements contaminated by misalignment
      noise.

PMID- 14649272
TI  - Interferential scanning grating position sensor operating in space at 4 K.
AB  - An interferential position sensor for operation in space at a deep cryogenic
      temperature (4 K) is derived from a commercial sensor. The application is for the
      Spectral and Photometric Imaging Receiver submillimetric imaging Fourier
      transform spectrometer on the Herschel space telescope. This sensor is used to
      control the displacement of the interferometer's moving mirrors and to sample the
      interferograms. This development addresses the following points: minimization of
      the effects of cooling critical optical parts, introduction of a fully redundant
      focal plane, selection of optoelectronic components efficient at 4 K, and design
      of a cryogenic preamplifier.

PMID- 14649273
TI  - Optical phase singularities in detection of laser beam collimation.
AB  - Optical phase singularities, also called optical vortices, are known to have
      applications in various branches of optics. Here the role played by optical
      vortices in collimation testing is explained. Interference and a diffractive
      experimental setup in which the presence of an optical vortex permits collimation
      testing are presented. It is shown that the moire fringes that aid in collimation
      detection are due solely to the presence of vortices and not to the accompanying
      phase factors that are involved in producing a grating structure.

PMID- 14649274
TI  - Design of a grating-based thin-film filter for broadband spectropolarimetry.
AB  - We propose a simple procedure for designing an integrated single-chip grating
      based thin-film filter. A simulation from a rigorous coupled-wave analysis shows
      that structural adjustment based on the effective medium theory can achieve the
      desired integration without notable performance degradation. Our
      spectropolarimetric filter design maintains spectral filter characteristics,
      while its extinction ratio is significantly enhanced over the passband. The
      integrated spectropolarimetric filter can be a basis for building multispectral
      multipolarimetric filters for spectropolarimetry in remote-sensing applications.

PMID- 14649275
TI  - Application of schlieren interferometry to temperature measurements during laser
      welding of high-density polyethylene films.
AB  - Schlieren interferometry is found to be an alternative tool for temperature
      measurement during thermoplastic laser welding with regard to methods based on
      thermocouples or optical pyrometers. In fact, these techniques are not easily
      applied when materials to be processed have reduced thickness, negligible heat
      conduction, and low emissivity, as is the case of welding high-density
      polyethylene films with 10.6-microm CO2 laser radiation, even if the method
      reaches its applicability limit after approximately 1 s of the interaction
      process. The schlieren method provides the means and the results to probe the
      thermal variations of the laser-thermoplastic interaction on both the surface and
      the interface between the sample material and the air.

PMID- 14649276
TI  - Application of wire-grid polarizers to projection displays.
AB  - We have measured the optical properties of wire-grid polarizers (WGPs). The
      implications of these results to the application of WGPs in projectors that use
      reflective light valves are discussed. In particular, the brightness and the
      contrast ratio of the projection system are investigated as functions of the
      angle of incidence of the light beam onto the WGP. It was found that the optimal
      incident angle is dependent on the physical design of the wire grids. In the
      sample that we describe, the optimal incident angle was 35 degrees instead of 45
      degrees. At the optimal incident angle, both the transmission and the reflection
      extinction ratios can be quite good. However, WGPs suffer from the drawback of
      free-carrier absorption by the metal grid.

PMID- 14649277
TI  - Mutual diffusion process for continuous fabrication of graded-index plastic rod
      lenses.
AB  - We propose a new process for fabrication of plastic rod lenses based on the
      traditional method of fiber extrusion. The process consists of the following
      steps: multilayer conjugate extrusion, monomer diffusion between adjacent layers,
      and photopolymerization of an uncured strand fiber. We call this process a mutual
      diffusion process for continuous plastic rod lens fabrication. Characteristics of
      this process are as follows: fast production speed (approximately 100 cm/min),
      precision control of refractive-index distribution, high angular aperture, and
      long-term reliability. The optical resolution of the rod-lens array is 300 dpi,
      which is high enough for application to G3 facsimiles with transmission time of
      less than 1 min and monochromatic scanners.

PMID- 14649278
TI  - Direct writing of microlenses in polycarbonate with excimer laser ablation.
AB  - A method for fabricating microlenses in polycarbonate material is reported. Using
      a direct-write technique based on scanning excimer laser ablation with a circular
      beam, we can etch an arbitrary shape in the polymer material. The beam is
      obtained by imaging a circular aperture onto the polymer surface, and scanning is
      realized by the translation stage carrying the sample, which makes successive
      contours with well-chosen diameters and scan velocities. Afterward, to smooth the
      ablated surface and release it from debris, a large beam aperture covering the
      full lens area is used to ablate the lens deeper into the substrate. The
      fabrication process and the characterization method are described, including
      calculation of the contour set for a desired lens shape. The optical performance
      is evaluated by Mach-Zehnder interferometry, showing that aberrations below
      lambda/10 are possible for slow lenses.

PMID- 14649279
TI  - Interferometric laser diode probing of micrometer- and nanometer-scale materials.
AB  - We are developing a method for real-time detection, tracking, and categorization
      of micrometer- and nanometer-scale particles and materials using light scattered
      from a swept standing-wave probe. Synchronous, phase-sensitive detection of the
      weakly scattered optical field is exploited to provide interferometric
      sensitivity and improve the signal-to-noise ratio, allowing use of low-power
      laser diode sources and photodiode detectors. To demonstrate the technique, we
      probe a set of W, C, and Cu microfibers and determine diameters and refractive
      index values from a detailed comparison of light-scattering data and a numerical
      model. We extrapolate these results and discuss the application of laser diode
      sources and photodiode receivers for the detection and study of nanoscale
      materials.

PMID- 14649280
TI  - Optical design of a spectrometer-monochromator for the extreme-ultraviolet and
      soft-x-ray emission of high-order harmonics.
AB  - A grazing-incidence spectrometer-monochromator for diagnostics and application of
      the extreme-ultraviolet (EUV) and soft-x-ray high-order harmonics generated by
      the interaction between a few-optical-cycle laser pulse and a gas jet has been
      fabricated. We address the necessity of high-resolution spectral and spatial
      analyses of the high-order harmonics as well as their use as short EUV
      backlighters in pump-probe experiments. The spectrometer that we present uses a
      variable-line-spaced flat grating illuminated in the converging light coming from
      a toroidal mirror. The spectrum is stigmatic, and the focal surface is almost
      flat in a wide spectral region. The detector is a microchannel plate intensifier
      with a phosphor screen optically coupled to a CCD camera; it can be moved by
      means of a linear drive to acquire different portions of the spectrum in the 5-75
      nm region. The resolution is almost limited by the pixel size of the detector. We
      apply the same optical scheme to achieve a constant-deviation-angle monochromator
      by substituting an exit slit for the detector block: The rotation of the grating
      gives the spectral scanning. A monochromator for the 5-50 nm spectral region is
      achieved.

PMID- 14649281
TI  - Measurement of extreme-ultraviolet attenuation edges of magnesium, tin, and
      indium filters.
AB  - We determined the energies of the Mg L2,3, Sn N4,5, and In N4,5 attenuation edges
      by measuring the transmission of high-resolution synchrotron radiation through
      thin filters. The Al L2,3 and Si L3 edges observed in the first and higher
      diffraction orders from the monochromator were used as energy fiducials. For each
      attenuation edge, the onset of attenuation with increasing energy and the
      inflection point of the attenuation curve were measured. The measured energy
      values were compared with previously determined attenuation edge energies and
      with electron binding energies. The measured energies of the inflection points
      are Mg L2 (49.89 +/- 0.02 eV), Mg L3 (49.58 +/- 0.02 eV), Sn N4 (25.00 +/- 0.02
      eV), Sn N5 (23.97 +/- 0.02 eV), In N4 (17.66 +/- 0.02 eV), and In N5 (16.70 +/-
      0.02 eV).

PMID- 14649282
TI  - Spectroscopic ellipsometry of metal phthalocyanine thin films.
AB  - Optical functions of cobalt phthalocyanine, nickel phthalocyanine (NiPc), and
      iron phthalocyanine (FePc) have been determined by use of spectroscopic
      ellipsometry in the spectral range 1.55-4.1 eV (300-800 nm). The samples were
      prepared by evaporation onto glass and silicon substrates. The optical functions
      were determined by point-to-point fit. Absorption spectra were also measured. The
      index-of-refraction data for NiPc and FePc are reported for the first time to our
      knowledge. Good agreement with the experimental spectra was obtained for all
      three materials.

PMID- 14649283
TI  - Angular distribution of light scattered by single biological cells and oriented
      particle agglomerates.
AB  - We used a flow cytometer together with an intensified CCD camera to record
      spatially resolved light scattering from micrometer-sized single particles and
      single oriented particle agglomerates. Experimental differential cross sections
      of an oriented dumbbell made from two identical polystyrene spheres were compared
      with theoretical values calculated within the discrete dipole approximation, and
      good agreement was achieved. Furthermore, characteristic two-dimensional patterns
      of the scattered-light intensity were recorded for single blood cells, yielding
      information on the cells' shape and volume. Besides flow cytometry, we observed
      and analyzed differential light scatter of particle clusters of known size,
      shape, and orientation located within an optical trap.

PMID- 14649284
TI  - Determination of the optical properties of a two-layer tissue model by detecting
      photons migrating at progressively increasing depths.
AB  - We have investigated a method for solving the inverse problem of determining the
      optical properties of a two-layer turbid model. The method is based on deducing
      the optical properties (OPs) of the top layer from the absolute spatially
      resolved reflectance that results from photon migration within only the top layer
      by use of a multivariate calibration model. Then the OPs of the bottom layer are
      deduced from relative frequency-domain (FD) reflectance measurements by use of
      the two-layer FD diffusion model. The method was validated with Monte Carlo FD
      reflectance profiles and experimental measurements of two-layer phantoms. The
      results showed that the method is useful for two-layer models with interface
      depths of >5 mm; the OPs were estimated, within a relatively short time (<1 min),
      with a mean error of <10% for the Monte Carlo reflectance profiles and with
      errors of <25% for the phantom measurements.

PMID- 14649285
TI  - Breast cancer detection by mapping hemoglobin concentration and oxygen
      saturation.
AB  - Near-infrared (NIR) spectroscopic imaging technology provides a new modality for
      measuring changes in total hemoglobin concentration (HbT) and blood oxygen
      saturation (SO2) in human tissue. The technology can be used to detect breast
      cancer because cancers may cause greater vascularization and greater oxygen
      consumption than in normal tissue. Based on the NIR technology, ViOptix, Inc.,
      has developed an optical device that provides two-dimensional mapping of HbT and
      SO2 in human tissue. As an adjunctive tool to mammography, the device was
      preliminarily tested in a clinical trial with 50 mammogram-positive patients at
      the Massachusetts General Hospital. The results of the clinical trial demonstrate
      that the device can reach as much as 92% diagnostic sensitivity and 67%
      specificity in detecting ductal carcinoma. These results may indicate that the
      NIR technology can potentially be used as an adjunct to mammography for breast
      cancer detection to reduce the number of biopsies performed.

PMID- 14649286
TI  - Endoscopic optical coherence tomography with a modified microelectromechanical
      systems mirror for detection of bladder cancers.
AB  - Experimental results of a modified micromachined microelectromechanical systems
      (MEMS) mirror for substantial enhancement of the transverse laser scanning
      performance of endoscopic optical coherence tomography (EOCT) are presented.
      Image distortion due to buckling of MEMS mirror in our previous designs was
      analyzed and found to be attributed to excessive internal stress of the
      transverse bimorph meshes. The modified MEMS mirror completely eliminates bimorph
      stress and the resultant buckling effect, which increases the wobbling-free
      angular optical actuation to greater than 37 degrees, exceeding the transverse
      laser scanning requirements for EOCT and confocal endoscopy. The new optical
      coherence tomography (OCT) endoscope allows for two-dimensional cross-sectional
      imaging that covers an area of 4.2 mm x 2.8 mm (limited by scope size) and at
      roughly 5 frames/s instead of the previous area size of 2.9 mm x 2.8 mm and is
      highly suitable for noninvasive and high-resolution imaging diagnosis of
      epithelial lesions in vivo. EOCT images of normal rat bladders and rat bladder
      cancers are compared with the same cross sections acquired with conventional
      bench-top OCT. The results clearly demonstrate the potential of EOCT for in vivo
      imaging diagnosis and precise guidance for excisional biopsy of early bladder
      cancers.

PMID- 14649287
TI  - Research progress and accomplishments on International Space Station.
AB  - The first research payloads reached the International Space Station (ISS) more
      than two years ago, with research operating continuously since March 2001. Seven
      research racks are currently on-orbit, with three more arriving soon to expand
      science capabilities. Through the first five expeditions, 60 unique NASA-managed
      investigations from 11 nations have been supported, many continuing into later
      missions. More than 90,000 experiment hours have been completed, and more than
      1,000 hours of crew time have been dedicated to research, numbers that grow
      daily. The multidisciplinary program includes research in life sciences, physical
      sciences, biotechnology, Earth sciences, technology demonstrations as well as
      commercial endeavors and educational activities. The Payload Operations and
      Integration Center monitors the onboard activities around the clock, working with
      numerous Principal Investigators and Payload Developers at their remote sites.
      Future years will see expansion of the station with research modules provided by
      the European Space Agency and Japan, which will be outfitted with additional
      research racks.

PMID- 14649288
TI  - Coverage of protein sequence space by current structural genomics targets.
AB  - By its purest definition the ultimate goal of structural genomics (SG) is the
      determination of the structures of all proteins encoded by genomes. Most of these
      will be obtained by homology modeling using the structures of a set of target
      proteins for experimental determination. Thanks to the open exchange of SG target
      information, we are able to analyze the sequences of the current target list to
      evaluate the extent of its coverage of protein sequence space. The presence of
      homologous sequences currently either in the Protein Data Bank (PDB) or among SG
      targets has been determined for each of the protein sequences in several
      organisms. In this way we are able to evaluate the coverage by existing or
      targeted structural data for the non-membranous parts of entire proteomes. For
      small bacterial proteomes such as that of H. influenzae almost all proteins have
      homologous sequences among SG targets or in the PDB. There is significantly lower
      coverage for more complex organisms, such as C. elegans. We have mapped the SG
      target list onto the ProtoMap clustering of protein sequences. Clusters occupied
      by SG targets represent over 150,000 protein sequences, which is approximately
      44% of the total protein sequences classified by ProtoMap. The mapping of SG
      targets also enables an evaluation of the degree of overlap within the target
      list. An SG target typically occupies a ProtoMap cluster with more than six other
      homologous targets.

PMID- 14649289
TI  - More for less in structural genomics.
AB  - Structural genomics is the idea of covering protein space so that every protein
      sequence comes within model building distance of a protein of known structure.
      Unfortunately, reproducing the structural alignment of distantly related proteins
      is a difficult challenge to existing sequence alignment and motif search
      software. We have developed a new transitive alignment algorithm (MaxFlow), which
      generates accurate alignments between proteins deep in the twilight zone of
      sequence similarity, below 20% sequence identity. In particular, MaxFlow reliably
      identifies conserved core motifs between proteins which are only indirect PSI
      Blast neighbours. Based on MaxFlow alignments, useful 3D models can be generated
      for all members of a superfamily from as few as a single structural template-
      despite hundreds of representatives at 40% sequence identity level and patchy
      detection of homology by PSI-Blast. We propose novel strategies for target
      prioritization using MaxFlow scores to predict the optimal templates in a
      superfamily. Our results support an increase in the granularity of covering
      protein space that has potentially enormous economic implications for planning
      the transition to the full production phase of structural genomics.

PMID- 14649290
TI  - Multi-domain protein families and domain pairs: comparison with known structures
      and a random model of domain recombination.
AB  - There is a limited repertoire of domain families in nature that are duplicated
      and combined in different ways to form the set of proteins in a genome. Most
      proteins in both prokaryote and eukaryote genomes consist of two or more domains,
      and we show that the family size distribution of multi-domain protein families
      follows a power law like that of individual families. Most domain pairs occur in
      four to six different domain architectures: in isolation and in combinations with
      different partners. We showed previously that within the set of all pairwise
      domain combinations, most small and medium-sized families are observed in
      combination with one or two other families, while a few large families are very
      versatile and combine with many different partners. Though this may appear to be
      a stochastic pattern, in which large families have more combination partners by
      virtue of their size, we establish here that all the domain families with more
      than three members in genomes are duplicated more frequently than would be
      expected by chance considering their number of neighbouring domains. This
      duplication of domain pairs is statistically significant for between one and
      three quarters of all families with seven or more members. For the majority of
      pairwise domain combinations, there is no known three-dimensional structure of
      the two domains together, and we term these novel combinations. Novel domain
      combinations are interesting and important targets for structural elucidation, as
      the geometry and interaction between the domains will help understand the
      function and evolution of multi-domain proteins. Of particular interest are those
      combinations that occur in the largest number of multi-domain proteins, and
      several of these frequent novel combinations contain DNA-binding domains.

PMID- 14649291
TI  - Characteristics and prediction of domain linker sequences in multi-domain
      proteins.
AB  - To facilitate swift structural characterizations, structural genomic/proteomic
      projects need to divide large multidomain proteins into structural domains and to
      determine their structures separately. Thus, the assignment of structural domains
      based solely on sequence information, especially on the physico-chemical
      properties of the amino acid sequences, could be very helpful for such projects.
      In this study, we examined the characteristics of 'domain linker sequences',
      which are loop sequences connecting two structural domains. To this end, we
      prepared a set of 101 non-redundant multi-domain protein sequences with known
      structures, and performed an analysis of the linker sequences. The analysis
      revealed that the frequencies of five (Pro, Gly, Asp, Asn, Lys) amino acid
      residues differed significantly between the linker and non-linker loop sequences.
      Moreover, we observed a similar deviation for the residue pair frequencies
      between the two types of loop sequences. Finally, we describe an automated
      method, based on the above analysis, to detect loops that have high probabilities
      of being domain linkers in a protein sequence.

PMID- 14649292
TI  - The German cDNA network: cDNAs, functional genomics and proteomics.
AB  - Among the greatest challenges facing biology today is the exploitation of huge
      amounts of genomic data, and their conversion into functional information about
      the proteins encoded. For example, the large-scale cDNA sequencing project of the
      German cDNA Consortium is providing vast numbers of open reading frames (ORFs)
      encoding novel proteins of completely unknown function. As a first step towards
      their characterization we have tagged over 500 of these with the green
      fluorescent protein (GFP), and examined the subcellular localizations of these
      fusion proteins in living cells. These data have allowed us to classify the
      proteins into subcellular groups which determines the next step towards a
      detailed functional characterization. To make further use of these GFP-tagged
      constructs, a series of functional assays have been designed and implemented to
      assess the effect of these novel proteins on processes such as cell growth, cell
      death, and protein transport. Functional assays with such a large set of
      molecules is only possible by automation. Therefore, we have developed, and
      adapted, functional assays for use by robotic liquid handling stations and
      reading stations. A transport assay allows to identify proteins which localize to
      distinct organelles of the secretory pathway and have the potential to be new
      regulators in protein transport, a proliferation assay helps identifying proteins
      that stimulate or repress mitosis. Further assays to monitor the effects of the
      proteins in apoptosis and signal transduction pathways are in progress.
      Integrating the functional information that is generated in the assays with data
      from expression profiling and further functional genomics and proteomics
      approaches, will ultimately allow us to identify functional networks of proteins
      in a morphological context, and will greatly contribute to our understanding of
      cell function.

PMID- 14649294
TI  - Automated multi-dimensional purification of tagged proteins.
AB  - The capacity for high throughput purification (HTP) is essential in fields such
      as structural genomics where large numbers of protein samples are routinely
      characterized in, for example, studies of structural determination, functionality
      and drug development. Proteins required for such analysis must be pure and
      homogenous and available in relatively large amounts. AKTA 3D system is a
      powerful automated protein purification system, which minimizes preparation, run
      time and repetitive manual tasks. It has the capacity to purify up to 6 different
      His6- or GST-tagged proteins per day and can produce 1-50 mg protein per run at
      >90% purity. The success of automated protein purification increases with careful
      experimental planning. Protocol, columns and buffers need to be chosen with the
      final application area for the purified protein in mind.

PMID- 14649293
TI  - Establishing the yeast Saccharomyces cerevisiae as a system for expression of
      human proteins on a proteome-scale.
AB  - Structural genomics requires the application of a standardised process for
      overexpression of soluble proteins that allows high-throughput purification and
      analysis of protein products. We have developed a highly parallel approach to
      protein expression, including the simultaneous expression screening of a large
      number of cDNA clones in an appropriate vector system and the use of a protease
      deficient host strain. A set of 221 human genes coding for proteins of various
      sizes with unknown structures was selected to evaluate the system. We transferred
      the cDNAs from an E. coli vector to the yeast expression vector by
      recombinational cloning, avoiding time-consuming recloning steps and the use of
      restriction enzymes in the cloning process. The subcloning yield was 95%,
      provided that a PCR fragment of the correct size could be obtained. Sixty percent
      of these proteins were expressed as soluble products at detectable levels and 48%
      were successfully purified under native conditions using the His6 tag fusion. The
      advantages of the developed yeast-based expression system are the ease of
      manipulation and cultivation of S. cerevisiae in the same way as with prokaryotic
      hosts and the ability to introduce post-translational modifications of proteins
      if required, thus being an attractive system for heterologous expression of
      mammalian proteins. The expression clones selected in this screening process are
      passed on to the fermentation process in order to provide milligram amounts of
      proteins for structure analysis within the 'Berlin Protein Structure Factory'.
      All data generated is stored in a relational database and is available on our
      website (http://www.proteinstrukturfabrik.de).

PMID- 14649295
TI  - Protein crystallization for genomics: throughput versus output.
AB  - Structural genomics involves many steps in order to reach from Gene to structure.
      This article focuses on the crystallization step in this chain of tasks. It is
      becoming increasingly evident that the current high throughput procedures for
      crystallising proteins do not always produce the expected output of high quality
      crystals required for structure determination by x-ray crystallography. This
      problem is discussed and suggestions for raising the output are presented.

PMID- 14649296
TI  - Secure web book to store structural genomics research data.
AB  - Recently established collaborative structural genomics programs aim at
      significantly accelerating the crystal structure analysis of proteins. These
      large-scale projects require efficient data management systems to ensure seamless
      collaboration between different groups of scientists working towards the same
      goal. Within the Berlin-based Protein Structure Factory, the synchrotron X-ray
      data collection and the subsequent crystal structure analysis tasks are located
      at BESSY, a third-generation synchrotron source. To organize file-based
      communication and data transfer at the BESSY site of the Protein Structure
      Factory, we have developed the web-based BCLIMS, the BESSY Crystallography
      Laboratory Information Management System. BCLIMS is a relational data management
      system which is powered by MySQL as the database engine and Apache HTTP as the
      web server. The database interface routines are written in Python programing
      language. The software is freely available to academic users. Here we describe
      the storage, retrieval and manipulation of laboratory information, mainly
      pertaining to the synchrotron X-ray diffraction experiments and the subsequent
      protein structure analysis, using BCLIMS.

PMID- 14649297
TI  - Structure-based functional inference in structural genomics.
AB  - The dramatically increasing number of new protein sequences arising from genomics
      and proteomics requires the need for methods to rapidly and reliably infer the
      molecular and cellular functions of these proteins. One such approach, structural
      genomics, aims to delineate the total repertoire of protein folds in nature,
      thereby providing three-dimensional folding patterns for all proteins and to
      infer molecular functions of the proteins based on the combined information of
      structures and sequences. The goal of obtaining protein structures on a genomic
      scale has motivated the development of high throughput technologies and protocols
      for macromolecular structure determination that have begun to produce structures
      at a greater rate than previously possible. These new structures have revealed
      many unexpected functional inferences and evolutionary relationships that were
      hidden at the sequence level. Here, we present samples of structures determined
      at Berkeley Structural Genomics Center and collaborators' laboratories to
      illustrate how structural information provides and complements sequence
      information to deduce the functional inferences of proteins with unknown
      molecular functions. Two of the major premises of structural genomics are to
      discover a complete repertoire of protein folds in nature and to find molecular
      functions of the proteins whose functions are not predicted from sequence
      comparison alone. To achieve these objectives on a genomic scale, new methods,
      protocols, and technologies need to be developed by multi-institutional
      collaborations worldwide. As part of this effort, the Protein Structure
      Initiative has been launched in the United States (PSI;
      www.nigms.nih.gov/funding/psi.html). Although infrastructure building and
      technology development are still the main focus of structural genomics programs,
      a considerable number of protein structures have already been produced, some of
      them coming directly out of semiautomated structure determination pipelines. The
      Berkeley Structural Genomics Center (BSGC) has focused on the proteins of
      Mycoplasma or their homologues from other organisms as its structural genomics
      targets because of the minimal genome size of the Mycoplasmas as well as their
      relevance to human and animal pathogenicity (http://www.strgen.org). Here we
      present several protein examples encompassing a spectrum of functional inferences
      obtainable from their three-dimensional structures in five situations, where the
      inferences are new and testable, and are not predictable from protein sequence
      information alone.

PMID- 14649298
TI  - Structural genomics efforts at the Chinese Academy of Sciences and Peking
      University.
AB  - Structural genomics efforts at the Chinese Academy of Sciences and Peking
      University are reported in this article. The major targets for the structural
      genomics project are targeted proteins expressed in human hematopoietic
      stem/progenitor cells, proteins related to blood diseases and other human
      proteins. Up to now 328 target genes have been constructed in expression vectors.
      Among them, more than 50% genes have been expressed in Escherichia coli,
      approximately 25% of the resulting proteins are soluble, and 35 proteins have
      been purified. Crystallization, data collection and structure determination are
      continuing. Experiences accumulated during this initial stage are useful for
      designing and applying high-throughput approaches in structural genomics.

PMID- 14649299
TI  - Structural genomics of highly conserved microbial genes of unknown function in
      search of new antibacterial targets.
AB  - With more than 100 antibacterial drugs at our disposal in the 1980's, the problem
      of bacterial infection was considered solved. Today, however, most hospital
      infections are insensitive to several classes of antibacterial drugs, and deadly
      strains of Staphylococcus aureus resistant to vancomycin--the last resort
      antibiotic--have recently begin to appear. Other life-threatening microbes, such
      as Enterococcus faecalis and Mycobacterium tuberculosis are already able to
      resist every available antibiotic. There is thus an urgent, and continuous need
      for new, preferably large-spectrum, antibacterial molecules, ideally targeting
      new biochemical pathways. Here we report on the progress of our structural
      genomics program aiming at the discovery of new antibacterial gene targets among
      evolutionary conserved genes of uncharacterized function. A series of
      bioinformatic and comparative genomics analyses were used to identify a set of
      221 candidate genes common to Gram-positive and Gram-negative bacteria. These
      genes were split between two laboratories. They are now submitted to a systematic
      3-D structure determination protocol including cloning, protein expression and
      purification, crystallization, X-ray diffraction, structure interpretation, and
      function prediction. We describe here our strategies for the 111 genes processed
      in our laboratory. Bioinformatics is used at most stages of the production
      process and out of 111 genes processed--and 17 months into the project--108 have
      been successfully cloned, 103 have exhibited detectable expression, 84 have led
      to the production of soluble protein, 46 have been purified, 12 have led to
      usable crystals, and 7 structures have been determined.

PMID- 14649300
TI  - Accurate and scalable identification of functional sites by evolutionary tracing.
AB  - A common difficulty in post genomics biology is that large-scale techniques of
      data collection often strip away information on the biological context of these
      data. The result is a massive number of disconnected observations on sequence,
      structure, and function from which underlying patterns and biological meaning are
      obscured. One solution is to build computational filters that pick out
      sufficiently few facts, relevant to a query, that their relationship is
      immediately apparent and experimentally testable. Typically, these filters rely
      on mathematics and statistics, and on first principles from physics and
      chemistry. We show here that evolution itself can be used to filter sequence and
      structure data in order to identify evolutionarily important amino acids. A
      general property of these residues is that they form clusters in native protein
      structures and point to regions where mutations have the greatest biological
      impact. The result is an accurate method of functional site annotation that is
      scalable for structural proteomics.

PMID- 14649301
TI  - From protein structure to biochemical function?
AB  - Here we describe various methods currently under development aimed at identifying
      a protein's function from its three-dimensional structure. We are combining a
      number of these methods to create a pipeline of applications, called ProFunc,
      which will take a given 3D structure, run all the applications on it and compile
      and summarise the results obtained. The aim is to provide a best guess as to the
      protein's function from the evidence provided by the different methods. Here we
      present three examples, using structures solved by the Midwest Center for
      Structural Genomics consortium, illustrating the strengths and weaknesses of
      current approaches.

PMID- 14649302
TI  - Influence of the completeness of chemical shift assignments on NMR structures
      obtained with automated NOE assignment.
AB  - Reliable automated NOE assignment and structure calculation on the basis of a
      largely complete, assigned input chemical shift list and a list of unassigned
      NOESY cross peaks has recently become feasible for routine NMR protein structure
      calculation and has been shown to yield results that are equivalent to those of
      the conventional, manual approach. However, these algorithms rely on the
      availability of a virtually complete list of the chemical shifts. This paper
      investigates the influence of incomplete chemical shift assignments on the
      reliability of NMR structures obtained with automated NOESY cross peak
      assignment. The program CYANA was used for combined automated NOESY assignment
      with the CANDID algorithm and structure calculations with torsion angle dynamics
      at various degrees of completeness of the chemical shift assignment which was
      simulated by random omission of entries in the experimental 1H chemical shift
      lists that had been used for the earlier, conventional structure determinations
      of two proteins. Sets of structure calculations were performed choosing the
      omitted chemical shifts randomly among all assigned hydrogen atoms, or among
      aromatic hydrogen atoms. For comparison, automated NOESY assignment and structure
      calculations were performed with the complete experimental chemical shift but
      under random omission of NOESY cross peaks. When heteronuclear-resolved three
      dimensional NOESY spectra are available the current CANDID algorithm yields in
      the absence of up to about 10% of the experimental 1H chemical shifts reliable
      NOE assignments and three-dimensional structures that deviate by less than 2 A
      from the reference structure obtained using all experimental chemical shift
      assignments. In contrast, the algorithm can accommodate the omission of up to 50%
      of the cross peaks in heteronuclear- resolved NOESY spectra without producing
      structures with a RMSD of more than 2 A to the reference structure. When only
      homonuclear NOESY spectra are available, the algorithm is slightly more
      susceptible to missing data and can tolerate the absence of up to about 7% of the
      experimental 1H chemical shifts or of up to 30% of the NOESY peaks.

PMID- 14649303
TI  - Patent protection for structural genomics-related inventions.
AB  - Recently there have been some important developments with respect to the
      patentability of inventions in the field of structural genomics. The leaders of
      the European Patent Office (EPO), Japan Patent Office (JPO) and the United States
      Patent Office (USPTO) came together for a trilateral meeting to conduct a
      comparative study on protein 3-dimensional (3-D) structure related claims in an
      effort to come to a mutual understanding about the examination of such
      inventions. The three patent offices were presented with eight different cases:
      1) 3-D structural data of a protein per se; 2) computer-readable storage medium
      encoded with structural data of a protein; 3) protein defined by its tertiary
      structure; 4) crystals of known proteins; 5) binding pockets and protein domains;
      6) and 7) are both directed to in silico screening methods directed to a specific
      protein; and 8) pharmacophores. The preliminary conclusions reached at the
      trilateral meeting provide clarity regarding the types of inventions that may be
      patentable given a specific set of scientific facts in a patent application.
      Therefore, the guidance provided by this study will help inventors, attorneys and
      other patent practitioners who file for patent protection on structural genomics
      based inventions both here and abroad comply with the patentability requirements
      of each office.

PMID- 14649304
TI  - Patenting nonassociated polymeric structures (NAPS): implications for structural
      genomic data release.
AB  - The intellectual property laws that govern patent rights should provide a
      reasonable balance between the competing concerns of open access and exclusivity.
      Open access can facilitate knowledge dissemination and collaboration in
      furthering science. On the other hand, exclusivity can ensure interest and
      financial investment in scientific research and development. In recent days, the
      appropriate balance between open access and exclusivity has been a focus of
      public debate, particularly with regard to genomic inventions and their
      applications. In seeking to reconcile the timing of structural genomic data
      release with certain efforts to secure intellectual property rights, the
      International Structural Genomics Organisation joins others confronting this
      controversy. This paper seeks to inform the discussion with an overview of the
      U.S. standards for patenting nonassociated polymeric structures (NAPS), which
      include polynucleotides or polypeptides of unknown biological significance, and
      their corresponding structural data. In the United States, the present ability to
      obtain patent rights to these discoveries appears problematic given the
      requirement of specific, substantial and credible utility, among other things.
      Without demonstrable utility, NAPS and NAPS-related data likely will not be
      entitled to patent protection, whether the U.S. Patent & Trademark Office rejects
      NAPS claims as unpatentable in the first instance, or the U.S. federal courts
      invalidate NAPS claims in later patent litigation. As such, the improbability of
      obtaining enforceable patent rights to NAPS might undermine the rationale for
      delaying structural genomic data release to allow for the filing of patent
      applications in this regard.

PMID- 14649305
TI  - Pulse pressure as a risk factor for peripheral vascular disease in type 2
      diabetic patients.
AB  - This study examined whether pulse pressure (PP) could be an independent predictor
      and associated with severity of peripheral vascular disease (PVD) in 396 type 2
      diabetic patients (143 men and 253 women, aged 64.1 +/- 11.2 years). Peripheral
      vascular disease was diagnosed by an ankle-brachial index (ABI) < 0.90 and as
      severe PVD if ABI < 0.80. Association was evaluated before and after adjustment
      for age, sex, diabetes duration, hypertension, smoking, fasting plasma glucose
      (FPG), total cholesterol (TC), usage of insulin, and usage of angiotensin
      converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB); and
      for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean
      arterial pressure (MAP), respectively. Results showed that PP increased from no
      (n = 348) to mild (n = 25) and severe (n = 23) PVD (one-way ANOVA, p < 0.001;
      multiple comparisons, p < 0.05 for any two groups). The PP increase from no to
      mild PVD was due to SBP increase; while further increase to severe PVD was due to
      both DBP drop and an even higher SBP. Adjusted odds ratio (AOR) for PVD for every
      1-mmHg PP increment was 1.035 (1.012-1.058). When PP was categorized as tertiles
      (< 50, 50-59 and > or = 60 mmHg), respective AOR for PVD for second and third vs.
      first tertile was 2.605 (1.008-6.729) and 2.835 (1.123-7.156). Pulse pressure was
      also predictive for ABI independent of the effects of the confounders and the
      other parameters of blood pressure. In conclusion, PP was an independent
      predictor and correlated with severity of PVD in type 2 diabetic patients.

PMID- 14649306
TI  - Efficacy of orthostatic self-training in medically refractory neurocardiogenic
      syncope.
AB  - BACKGROUND: Orthostatic self-training is effective in the prevention of
      neurocardiogenic syncope, though the success of this method in drug refractory
      patients has not been reported. STUDY OBJECTIVE AND METHODS: This study examined
      the effectiveness of orthostatic self-training in 15 patients with head-up tilt
      testing (HUT)-inducible neurocardiogenic syncope, who were intolerant of, or
      refractory to standard drug therapy. They were enrolled in a home orthostatic
      self-training program for up to 30 min/session, twice daily. Head-up tilt testing
      was repeated within 4 weeks after onset of the training program, using the same
      protocol as at baseline. Orthostatic self-training was continued once daily, for
      up to 30 min, for a mean follow-up period of 11 months, in the drug-free state.
      RESULTS: Syncope was not reinducible by follow-up HUT, and spontaneous syncope
      occurred in no patient during the follow-up period. CONCLUSIONS: Home orthostatic
      self-training, up to 30 min once daily following an initial twice daily program,
      was highly effective in the suppression of recurrent neurocardiogenic syncope in
      patients intolerant of, or refractory to standard drug therapy.

PMID- 14649307
TI  - Effect of dietary calcium supplements and amlodipine on growth, arterial blood
      pressure, and cardiac hypertrophy of spontaneously hypertensive rats.
AB  - It has been shown that calcium-enriched diets cause a decrease in arterial blood
      pressure in hypertensive patients and animals. Moreover, it has been suggested
      that the combination of dietary calcium and calcium antagonists could
      paradoxically have a synergistic effect in order to decrease arterial blood
      pressure. The combination of these treatments may also have potential therapeutic
      benefit in the attenuation of cardiac hypertrophy. In this study, after being
      weaned at three weeks, male spontaneously hypertensive rats (SHR) were randomized
      in four groups of animals. Two of these groups were fed on a normal calcium diet
      (Ca 1%) and another two groups were fed on a calcium-enriched diet (Ca 2.5%). One
      of the groups fed on each diet also received amlodipine (1 mg/kg/day) in the
      drinking water after being weaned. Body weight was measured weekly in all the
      groups, and arterial blood pressure was also measured in all the 10-, 15-, 20-,
      and 25-week-old SHR by the tail cuff method. We established the ratio heart
      weight/body weight x 1000 (R), and we weighed the left ventricle in the 25-week
      old animals at the end of the different treatments. The Ca 2.5% diet caused a
      delay in the development of hypertension in SHR. This effect could not be
      correlated with alterations in body weight since this diet improved growth in
      these rats. Amlodipine did not alter growth in SHR. This pharmacological
      treatment caused a decrease in the arterial blood pressure of the SHR and it
      intensified the antihypertensive effect of the Ca 2.5% diet. Nevertheless, this
      drug attenuated the effect of dietary calcium on body weight and when the
      treatment was prolonged, almodipine also antagonized the effect of dietary
      calcium on arterial blood pressure. At the end of the different treatments the
      ratio R and the left ventricular weight were similar in all the groups of
      animals. Therefore, the use of dietary calcium with a calcium antagonist to
      control arterial blood pressure seems not to be advisable, and the present data
      do not prove the usefulness of the mentioned antihypertensive treatments in
      preventing cardiac hypertrophy.

PMID- 14649308
TI  - Diminished natriuretic response to dopamine D1 receptor agonist, SKF-38393 in
      obese Zucker rats.
AB  - Dopamine causes natriuresis and diuresis via activation of D1 receptors located
      on the renal proximal tubules and subsequent inhibition of the sodium
      transporters, Na-H exchanger and Na+/K+ ATPase. We have reported that dopamine
      fails to inhibit the activities of these two transporters in the obese Zucker
      rats (OZR). The present study was designed to examine the functional consequence
      of this phenomenon by determining the natriuretic and diuretic response to D1
      receptor activation in lean Zucker rats (LZR) and OZR. In 11-12 week-old OZR and
      LZR, natriuretic and diuretic responses to intravenously administered D1 receptor
      agonist, SKF 38393 (3 microg/kg/min for 30 min) were measured under Inactin
      anesthesia. Plasma insulin and glucose levels were significantly higher in the
      obese rats as compared to the lean rats. Intravenous infusion of SKF 38393 caused
      significant increases in urine flow, urinary sodium excretion (U(Na)V),
      fractional excretion of sodium (FE(Na)), and glomerular filtration rate (GFR) in
      the lean rats. However, the natriuretic and diuretic response to SKF 38393 was
      markedly blunted in OZR. Infusion of SKF 38393 did not cause significant changes
      in the mean blood pressure and heart rate in either of the two groups. We suggest
      that the diminished natriuretic response to D1 receptor activation in OZR is the
      consequence of the previously reported defect in the D1 receptor-G-protein
      coupling and the failure of dopamine to inhibit the sodium transporters in these
      animals.

PMID- 14649309
TI  - Patients with essential hypertension present higher levels of sE-selectin and
      sVCAM-1 than normotensive volunteers.
AB  - In essential hypertension (EH) patients, blood pressure can modify serum
      concentrations of some soluble forms of cell adhesion molecules (CAM), e.g.,
      soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule-1
      (sVCAM-1). The objective of this study was to compare the serum levels of these
      CAMs in compensated (CH) and non-compensated (NCH) EH patients. Our findings show
      that sE-selectin and sVCAM-1 levels are higher in EH patients than normotensive
      subjects (sVCAM-1: 796+/-52 vs. 605+/-24 ng/mL, p<0.0001, and sE-selectin: 71+/
      21 vs. 48+/-14 ng/mL, p<0.0001). Serum concentrations of both CAMs was higher in
      NCH patients than CH patients. High arterial blood pressure (ABP) may therefore
      increase the production of cell adhesion molecules, probably through endothelial
      activation.

PMID- 14649310
TI  - Effects of calcium channel antagonists on left ventricular hypertrophy and
      diastolic function in patients with essential hypertension.
AB  - Hypertensive patients characteristically exhibit left ventricular (LV)
      hypertrophy and diastolic dysfunction. The effects of antihypertensive agents on
      LV hypertrophy and diastolic dysfunction do not always correlate with the degree
      of blood pressure reduction, but their effects on the sympathetic nervous system
      and renin-angiotensin system (RA system) are thought to be important. We
      investigated the effects of amlodipine and cilnidipine, N- and L-type calcium
      channel antagonists that suppress both blood pressure elevation and sympathetic
      activities, on LV hypertrophy and diastolic function. Patients with essential
      hypertension were randomly assigned to receive either amlodipine, cilnidipine or
      nifedipine CR (which does not block N-type calcium channels) for 6 months. The LV
      mass index was determined using M-mode echocardiography. The E/A ratio, i.e., the
      ratio of maximum amplitude between the early diastolic wave (E wave) and the
      atrial systolic wave (A wave) in the LV inflow pattern, and the deceleration time
      for the E wave were determined using pulse Doppler echocardiography. Systolic and
      diastolic blood pressures significantly decreased from the baseline values in all
      three groups, with no significant differences among the groups. The LV mass index
      had significantly decreased when it was evaluated 3 months after the initiation
      of treatment in the cilnidipine group and when it was evaluated 6 months after
      the initiation of treatment in the amlodipine group; only a slight decrease was
      observed in the nifedipine CR group. A significant decrease in the deceleration
      time and a significant increase in the E/A ratio were observed after 3 months of
      treatment in the cilnidipine and amlodipine groups but not in the nifedipine CR
      group. Thus, the effects of long-acting calcium channel antagonists on
      hypertensive LV hypertrophy and LV diastolic function varied from one antagonist
      to the other. Left ventricular hypertrophy and diastolic function improved in the
      cilnidipine and amlodipine groups, but not in the nifedipine CR group. These
      results indicate that the suppression of sympathetic nerve activity by the
      blockade of N-type calcium channels contributes to the improvement of LV
      hypertrophy and diastolic function.

PMID- 14649311
TI  - A different molecular pattern of beta-thalassemia mutations in northeast Brazil.
AB  - The main hereditary hemoglobin (Hb) disorders of clinical significance in Brazil
      are sickle cell disease and beta-thalassemia (thal). The sickle gene was
      introduced by the slave trade, whereas beta-thal was introduced later, due to a
      massive immigration (mostly by Italians) between 1870 and 1953, mainly to the
      southeast region of Brazil. Molecular studies performed in the southeast of the
      country showed a marked prevalence of the nonsense mutation at codon 39 (C --> T)
      (47-54%), leading to severe forms of beta0-thal. However, the northeast region of
      the country has a different demographic history, characterized by the absence of
      the massive Italian immigration. Owing to this and since the majority of cases of
      beta-thal in Pernambuco, a state located in the northeast of the country, have
      mild or intermediate clinical and laboratory features, we would predict a
      different spectrum of beta-thal mutations in this region. We examined 60
      unrelated patients (86 beta-thal chromosomes) under regular clinical follow-up in
      Pernambuco: 6 were regularly transfused beta-thal major subjects, 20 had beta
      thal intermedia, 20 had Hb S/beta-thal and 14 were beta-thal trait individuals.
      The following mutations were found: IVS-I-6 (T --> C) 62.8%, IVS-I-1 (G -->A)
      15.1%, IVS-I-5 (G --> C) 9.3%, IVS-I-110 (G --> A) 8.2%, codon 39 (C --> T) 3.5%,
      and codon 30 (AGG --> AGC) 1.1%. These data show different patterns of beta-thal
      mutations in two regions of Brazil, demonstrating a thus far unrevealed
      heterogeneity of the disease in the country.

PMID- 14649312
TI  - delta-Globin gene structure and expression in the K562 cell line.
AB  - The delta-globin gene produces the delta chain of Hb A2 which represents less
      than 3% of the hemoglobin (Hb) in normal individuals. The delta-globin gene is
      also expressed in the human erythroleukemia cell line K562. The expression of the
      delta-globin gene in this cell line is unexpected since K562 shows an embryonic
      fetal globin gene expression pattern with no expression of the adult beta-globin
      gene. delta-Globin gene activation has been proposed as a potential therapeutic
      tool for the cure of delta-thalassemia (thal). In order to shed some light on the
      delta-globin gene activation in K562 the present study has: (1) determined the
      complete nucleotide sequence of the delta- and beta-globin genes; (2) assessed,
      by reverse transcription-polymerase chain reaction (RT-PCR), the relative delta-
      and beta-globin mRNA level; and (3) analyzed the exact level of the endogenous
      expression delta-globin gene by S1 mapping. No sequence variations were
      identified in the (delta- and beta-globin genes when compared to the normal
      sequences. delta-Globin mRNA represent more than 95% of the total delta + beta
      mRNA content. The level of expression of the delta-globin gene is 12.3% (+/- 1.2)
      compared to the endogenous alpha-globin gene. These results indicate that the
      high expression of the delta-globin gene in K562 is most likely due to the
      transacting environment. Therefore, the presence and/or absence of specific
      transacting factors are able to specifically activate the human delta-globin
      gene. The level of expression of the delta-globin gene in this cell line suggests
      that it could be of relevance to identify the transacting factor(s) responsible
      for this selective activation in order to better understand the molecular
      mechanisms undergoing gene activation.

PMID- 14649313
TI  - Production of murine monoclonal antibody to fetal hemoglobin.
AB  - Fetal hemoglobin (Hb F) is a major hemoglobin (Hb) component at birth. Hb F
      levels are markedly elevated in a number of inherited and acquired disorders.
      Measurement of Hb F levels is usually carried out by alkali denaturation which is
      not very accurate for low and high values. An accurate estimation of Hb F, and
      also of F cells, is desired in many hematological disorders like sickle cell
      disease, in monitoring the efficacy of hydroxyurea (HU) therapy, to assess feto
      maternal hemorrhage (FMH) during pregnancy and in the postpartum period. We have
      raised a murine monoclonal antibody to human Hb F, that accurately measures the
      number of F cells by flow cytometry. The antibody was found to be potent and
      specific for F cells.

PMID- 14649314
TI  - Three new hemoglobin variants with abnormal oxygen affinity: Hb Saratoga Springs
      [alpha40(C5)Lys --> Asn (alpha1)], Hb Santa Clara [beta97(FG4)His --> Asn], and
      Hb Sparta [beta103(G5)Phe --> Val].

PMID- 14649315
TI  - Hb Buzen [beta138(H16)Ala --> Thr (g.1395 G -->A)]: a new beta chain variant.

PMID- 14649316
TI  - Hb Setif [alpha94(G1)Asp --> Tyr (alpha2)] detected in a Turkish family.

PMID- 14649317
TI  - Hb Castilla [beta32(B14)Leu --> Arg] caused by a de novo mutation.

PMID- 14649318
TI  - Mild Hb S-beta(+)-thalassemia with a deletion of five nucleotides at the
      polyadenylation site of the beta-globin gene.

PMID- 14649319
TI  - A new alpha2-globin gene [codon 90 (AAG --> TAG)] nonsense mutation.

PMID- 14649320
TI  - Differential segregation of beta+ IVS-I-110 (G --> A), A(gamma) -117 (G-->A), and
      G(gamma) -158 (C --> T) mutations in members of an Albanian family.

PMID- 14649321
TI  - Molecular basis of beta-thalassemia mutations in Diyarbakir in the southeastern
      region of Turkey.

PMID- 14649322
TI  - Development of surgery during the last 50 years.

PMID- 14649323
TI  - Radiosensitivity in lung cancer with focus on p53: a review based on a doctoral
      thesis.

PMID- 14649324
TI  - Oral immunotherapy with yolk antibodies to prevent infections in humans and
      animals.
AB  - There is an increasing prevalence of antibiotic-resistant bacteria, which makes
      traditional antibiotics less effective. It is thus important to find an
      alternative to the use of antibiotics. Oral administration of specific antibodies
      is an attractive approach to establish protective immunity against
      gastrointestinal pathogens in humans and animals. Immunotherapy can also be used
      against pathogens that are difficult to treat with traditional antibiotics.
      Laying hens are good producers of specific antibodies. After immunisation, the
      specific antibodies are transported to the egg yolk from which the antibodies
      (IgY) can be purified in large quantities. Eggs are also normal dietary
      components and thus there is practically no risk of toxic side effects of IgY.
      Yolk antibodies have been shown in several studies to prevent both bacterial and
      viral infections. We have treated one patient with yolk antibodies against P.
      aeruginosa daily for more than eight years, which shows that it is possible to
      use yolk immunotherapy over long treatment periods.

PMID- 14649325
TI  - Nimodipine affects the microcirculation and modulates the vascular effects of
      acetylcholinesterase inhibition.
AB  - The present investigation was undertaken in order to study whether microvascular
      effects of the calcium antagonist nimodipine induces changes that can explain an
      increased detoxification of the highly toxic cholinesterase inhibitor soman.
      Anaesthetised, tracheotomised and artificially ventilated rats were treated intra
      peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour
      later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a
      vasodilation in the intestine, myocardium and other muscles. In the abdominal
      skin soman elicited a significant vasoconstriction that was turned into an
      increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in
      diaphragm of soman intoxicated rats was turned into a significant vasodilation by
      nimodipine pre-treatment. In the intestinal parts no effect of soman was
      detected. However, in nimodipine pretreated animals soman induced a significant
      vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic
      hydrolysis and covalent binding to different esterases, is unequally distributed
      throughout the body. Together with the knowledge of the detoxifying processes of
      cholinesterase inhibition the results support our theory, that nimodipine alters
      the peripheral blood flow in a beneficial way resulting in improved
      detoxification ability.

PMID- 14649326
TI  - Synovial sarcoma with massive ossification--a case report.
AB  - Synovial sarcoma with extensive osteoid production is rare. We report a case of
      synovial sarcoma of monophasic type with massive ossification. The diagnosis was
      confirmed by reverse-transcripitase polymerase chain reaction (RT-PCR). The
      patient was an-81-year-old woman with recurrent synovial sarcoma in her right
      knee. The tumor was primarily excised in 1989. It recurred and was removed again
      in 1996. However, in 1999 a painful mass appeared in the same site. Preoperative
      plain radiography and computed tomography revealed a 5 x 5 cm soft tissue mass
      with extensive ossification in the medial side of the right knee joint. The tumor
      was widely excised in 2000. Soft X-ray examination revealed a trabecular pattern
      of ossification in the excised tumor. Microscopically the tumor was composed of
      hypercellular spindle cells with fascicular arrangement with prominent
      ossification but no epithelial component. The tumor cells were positive for
      vimentin and focally positive for cytokeratin. The tumor expressed a sequence of
      SYT-SSX1 fusion gene transcript demonstrated by RT-PCR. Twelve years long
      survival of the present case without metastasis in spite of repeated recurrence
      suggests a better prognosis of synovial sarcomas with ossification.

PMID- 14649327
TI  - The role of epidermal growth factor receptor in advanced non-small cell lung
      carcinoma.
AB  - Chemotherapy is the standard of care for patients with advanced non-small cell
      lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown
      minimal incremental improvement in the survival outcomes of patients with
      advanced NSCLC. With the identification of molecular and genetic alterations in
      lung cancer, several new potential rationally designed therapeutic targets have
      emerged. One of these is the epidermal growth factor receptor (EGFR) and member
      of the ErbB family of receptor tyrosine kinases. Several inhibitors, both
      antibodies directed at the extra-cellular portion of the receptor, and small
      molecule inhibitors directed at the tyrosine kinase domain of EGFR are in
      clinical development in lung cancer. This article will review the pre-clinical
      rationale and the clinical studies of EGFR inhibitors alone and/or in combination
      with chemotherapy that have been performed to date in advanced NSCLC.

PMID- 14649328
TI  - Novel cancer therapy by reactivation of the p53 apoptosis pathway.
AB  - The p53 transcription factor prevents tumor development through induction of cell
      cycle arrest and cell death by apoptosis. As many as several hundred genes or
      more are regulated by p53. Around half of all human tumors carry p53 mutation,
      mostly point mutations that abrogate p53's specific DNA binding and
      transactivation activity. p53 mutation is associated with poor therapeutic
      response and prognosis. Tumors that carry wild type p53 often have other
      alterations in the p53 pathway that ablate the p53 response. Several strategies
      have been designed to restore p53 function in human tumors, including p53 gene
      therapy, reactivation of mutant p53, and activation of wild type p53 by
      inhibition of the p53 antagonist MDM2. In all cases, the aim is to eliminate the
      tumor through induction of massive apoptosis.

PMID- 14649329
TI  - Telomerase as a novel and potentially selective target for cancer chemotherapy.
AB  - Telomeres are the structures that protect eukaryotic chromosomes from recognition
      by DNA damage surveillance mechanisms and are maintained in the germ line of
      multicellular animals by telomerase. In most human somatic cells telomerase is
      silenced during development and after extensive cell division telomeres shorten
      to trigger growth arrest. Around 80% of human cancers escape from this growth
      arrest by re-activating telomerase but at diagnosis many cancers still have very
      short telomeres making them very vulnerable to the inhibition of telomerase. As
      normal cells have a considerable telomere reserve, even in elderly humans, this
      makes telomerase an attractive and potentially selective anti-cancer drug target.
      Proof-of-principle experiments are reviewed which show that this optimism may be
      justified at least for the subset of human cancers with short telomeres. I also
      address many of the commonly raised concerns that surround telomerase as a target
      for anti-cancer drug design.

PMID- 14649330
TI  - Non steroidal anti-inflammatory drugs and COX-2 inhibitors as anti-cancer
      therapeutics: hypes, hopes and reality.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and specific inhibitors of
      cyclooxygenase (COX)-2, are therapeutic groups widely used for the treatment of
      pain, inflammation and fever. There is growing experimental and clinical evidence
      indicating NSAIDs and COX-2 inhibitors also have anti-cancer activity.
      Epidemiological studies have shown that regular use of Aspirin and other NSAIDs
      reduces the risk of developing cancer, in particular of the colon. Molecular
      pathology studies have revealed that COX-2 is expressed by cancer cells and cells
      of the tumor stroma during tumor progression and in response to chemotherapy or
      radiotherapy. Experimental studies have demonstrated that COX-2 over expression
      promotes tumorigenesis, and that NSAIDs and COX-2 inhibitors suppress
      tumorigenesis and tumor progression. Clinical trials have shown that NSAIDs and
      COX-2 inhibitors suppress colon polyp formation and malignant progression in
      patients with familial adenomatous polyposis (FAP) syndrome. Recent advances in
      the understanding of the cellular and molecular mechanisms of the anti-cancer
      effects of NSAIDs and COX-2 inhibitors have demonstrated that these drugs target
      both tumor cells and the tumor vasculature. The therapeutic benefits of COX-2
      inhibitors in the treatment of human cancer in combination with chemotherapy or
      radiotherapy are currently being tested in clinical trials. In this article we
      will review recent advances in the understanding of the anti-tumor mechanisms of
      these drugs and discuss their potential application in clinical oncology.

PMID- 14649331
TI  - A practice guideline for treatment of eating disorders in children and
      adolescents.
AB  - Eating disorders are diseases of both the body and the psyche. Early treatment
      focuses on restoration of nutritional status and somatic health, including psycho
      educational counselling and support offered to the patient and his/her family.
      Diagnosis and treatment require a multidisciplinary approach. Psychological
      factors related to the condition should be assessed. The most severe weight loss
      should be reversed before psychotherapeutic treatment. Nutritional counselling is
      recommended, and the benefits of individual and/or family therapy are considered
      in accordance with the patient's age, development, symptomatology and comorbid
      psychiatric disorders. Medication is useful in the treatment of bulimia nervosa
      and certain comorbid symptoms of anorexia nervosa. Early admission to treatment
      and active therapy are associated with a more favourable prognosis.

PMID- 14649332
TI  - Sitosterolemia: a gateway to new knowledge about cholesterol metabolism.
AB  - Sitosterolemia (OMIM 210250) is a rare, autosomal recessive lipid disorder
      initially described almost 30 years ago. The disease is characterized by elevated
      plasma levels of plant sterols due to increased intestinal absorption and reduced
      biliary secretion of neutral sterols. Patients with sitosterolemia are frequently
      hypercholesterolemic, and develop xanthomas and premature coronary heart disease
      (CHD). Hemolysis, arthralgias and arthritis are also frequently associated with
      the disorder. Recently, sitosterolemia has been revealed to be due to mutations
      in either of the two ATP-binding cassette (ABC) half-transporters. ABCG5 or
      ABCG8. These two genes are expressed almost exclusively in the liver and
      intestine, and are co-regulated by the nuclear hormone receptor, liver X receptor
      (LXR). Genetically modified mice, which express either high levels or no ABCG5
      and ABCG8 have been developed. Analyses of these mice confirm that these two
      transporters play key roles in regulating the absorption of dietary and biliary
      sterols, and in mediating the excretion of neutral sterols from the liver to the
      bile. The elucidation of the gene defects responsible for sitosterolemia provides
      potential therapeutic targets for the treatment of hyperlipidemias in the general
      population.

PMID- 14649333
TI  - GnRH antagonists in the treatment of infertility.
AB  - GnRH analogues were introduced into clinical practice more than 20 years ago. The
      recent development of new GnRH antagonists (GnRHant) has revolutionized the
      treatment protocols of infertility. Ovarian stimulation has become easier, safer
      and more convenient for patients. This review presents data on the physiological
      background of GnRH and its analogues--agonists as well as antagonists--and
      highlights the different aspects of the clinical use of these substances. Two
      protocols, the single dose and multiple dose protocol are available and lead to
      comparable results. Data from prospective, randomized trials as well as meta
      analyses suggest, that a more tailored, individualized approach concerning the
      day of administration of GnRHant may lead to more favorable results with regard
      to ovarian response, implantation and pregnancy rates. Possible negative effects
      of GnRHant, mainly based on in vitro models are discussed. The outcome of
      children born after GnRHant use has shown, that this medication is safe. On the
      whole, the use of GnRHant is advantageous as compared to the traditional way of
      ovarian stimulation, i.e., the GnRH agonist long protocol. However, especially
      the effectiveness of these compounds will have to be clarified in the near future
      by carefully designed prospective, randomized studies.

PMID- 14649334
TI  - Inflammation and restenosis: implications for therapy.
AB  - Restenosis is the process of luminal narrowing in an atherosclerotic artery after
      an intra-arterial intervention such as balloon angioplasty and stenting. It is
      believed that this process is mainly characterized by migration and proliferation
      of smooth muscle cells and extracellular matrix accumulation. However, there is
      now increasing evidence for a role of inflammation in the development of
      restenosis. The underlying molecular mechanisms of restenosis are, in fact, most
      probably regulated by inflammatory mediators, such as cytokines. Understanding
      the molecular mechanisms in restenosis is crucial for the development of a
      suitable therapy for this disease. Recently, the use of immunosuppressives in
      drug-eluting stents has provided very promising results in the treatment of
      restenosis. In this review, we will describe the molecular mechanisms involved in
      restenosis with a focus on the role of inflammation and the use of
      immunosuppressive therapy.

PMID- 14649335
TI  - Confounding, ascertainment bias, and the blind quest for a genetic 'fountain of
      youth'.
AB  - Many promises have been made about the impact of the Human Genome Project on
      clinical practice and public health, yet despite massively funded efforts over
      the past decade, little headway has been made in elucidating the specific genetic
      factors which have major impact on the risk of developing common complex traits.
      There are two fundamental reasons for this abject failure as follows: 1) studies
      have been inadequately designed to identify such genetic risk factors; 2) the
      genetic factors that do exist are individually of small marginal importance, and
      are characterized by extensive heterogeneity. If 2) is the truth, there is little
      we can do about it, so we emphasize the importance of 1) in this article, while
      recognizing that 2) probably is not far from the truth. Genetic studies, in
      contrast to epidemiological studies, use confounding and ascertainment bias to
      help identify weak etiologic signal due to genes, since gene mapping is
      fundamentally a hypothesis-free science. This strategy makes it possible to
      identify genetic risk factors, but makes it impossible to quantify the size of
      their effect on risk. Classical epidemiological study designs are of minimal
      value for gene identification, but may be of use in estimation of the effect size
      of genetic risk factors once they are identified in more appropriately designed
      genetic studies. However, if the effects are so weak that we need this strong,
      systematic ascertainment bias to find them, their relevance to public health may
      be of questionable immediate value, raising many questions about the rhetoric and
      promises being made to the public as justification for 'big science' approaches
      to dissecting the hypothetical role of genes in complex traits.

PMID- 14649336
TI  - Non-heart-beating organ donation.

PMID- 14649337
TI  - Anaesthetic implications of anticancer chemotherapy.
AB  - In anaesthetic practice we deal with cancer patients who are scheduled for
      operations on tumours or other manifestations of malignant disease. Those
      patients are often debilitated and have significant weight loss accompanied with
      hypoproteinaemia, anaemia and coagulation disorders. Oncological patients usually
      present to the anaesthetist before tumour disease surgery, but they are also
      candidates for elective operations (e.g. hernia repair) and urgent/emergency
      surgery (e.g. trauma, fractures and ileus). Chemotherapeutic agents given to
      these patients are potentially noxious, can affect the conduct of anaesthesia
      and, furthermore, may aggravate the patient's condition. In this review the most
      commonly used cytostatic drug regimens and their common side-effects are listed.
      Some preclinical studies on anaesthetic and cytostatic drug metabolism and
      interactions are emphasized, as well as clinically relevant perioperative
      alterations that may affect anaesthetic management in cancer patients. An
      anaesthetist may have to modify a routine anaesthetic regimen in cancer patients
      especially if anticancer chemotherapeutics were given. Clinically silent toxic
      drug effects may become apparent during operation, trauma or in the early
      postoperative course in such patients. Altered reactions to commonly used
      anaesthetics in patients receiving chemotherapeutics and an impaired stress
      reaction may occur in such patients. Special attention must be drawn to
      protection against opportunistic infections.

PMID- 14649338
TI  - The 'TEI-index' is preload dependent and can be measured by transoesophageal
      echocardiography during mechanical ventilation.
AB  - BACKGROUND AND OBJECTIVE: The Doppler-derived echocardiographic TEI-index,
      defined as the sum of the left ventricular isovolumic contraction and isovolumic
      relaxation times divided by ejection time, quantifies combined systolic and
      diastolic ventricular functions. The index has been proposed to be independent of
      arterial pressure and heart rate, implying a broad clinical usefulness. However,
      it is unclear whether the index is preload independent. We assessed whether and
      to what degree the TEI-index is altered by left ventricular loading conditions,
      and the feasibility of measurement by transoesophageal echocardiography during
      anaesthesia and mechanical ventilation. METHODS: We studied 17 anaesthetized
      mechanically ventilated patients with coronary artery disease during variations
      in left ventricular preload evoked by head-up and head-down tilt, respectively.
      RESULTS: A head-down tilt increasing left ventricular end-diastolic area from
      18.8 +/- 4 to 23.7 +/- 4 cm2 (P < 0.05) significantly decreased the TEI-index
      from 0.5 +/- 0.17 to 0.33 +/- 0.15 (P < 0.05). In contrast, the TEI-index
      remained unchanged with decreased left ventricular preload (14.4 +/- 3.7 cm2)
      during head-up tilt. CONCLUSIONS: An increase in preload decreases the TEI-index
      indicating its sensitivity to acute increases in left ventricular preload. The
      TEI-index can be measured perioperatively by transoesophageal echocardiography.

PMID- 14649339
TI  - Desflurane inhibits platelet function in vitro similar to halothane.
AB  - BACKGROUND AND OBJECTIVE: The effects of the volatile anaesthetic desflurane on
      platelet activation in vitro were studied and compared to those of halothane.
      METHODS: Platelet-rich plasma was exposed to 2 MAC of desflurane or halothane, or
      air only and stimulated by platelet agonists ADP (2.5, 5 and 10 micromol L(-10)
      and collagen (10 microg m(L-1)). Platelet response was measured by Born
      aggregometry (maximum aggregation response, area under the curve) and flow
      cytometry (mean channel fluorescence, percentage of CD62P-positive cells, index
      of platelet activation for positive platelets). RESULTS: Aggregation response was
      significantly reduced in platelets exposed to desflurane or halothane; the
      inhibitory effect was more pronounced when the areas under the curve were
      analysed: values ranged from 37.5% to 73.3% of control samples for ADP
      stimulation and 77.1% to 79.8% for collagen stimulation. CD62P expression before
      and after stimulation with receptor agonists was not statistically different in
      platelets exposed to desflurane, halothane or air. CONCLUSIONS: By impairing
      platelet aggregation while not affecting alpha-degranulation desflurane has a
      differential effect on various aspects of platelet activation similar to
      halothane. Our results are compatible with the hypothesis of an impairment of
      platelet thromboxane receptor signalling by halothane. We suggest a similar
      mechanism for desflurane.

PMID- 14649340
TI  - Implications of the use of neuromuscular transmission monitoring on immediate
      postoperative extubation in off-pump coronary artery bypass surgery.
AB  - BACKGROUND AND OBJECTIVE: When continuous infusions of neuromuscular blocking
      drugs are administered during lengthy interventions and no routine antagonism of
      their effects is applied, there is a dramatic incidence of residual curarization.
      We have examined whether the use of neuromuscular transmission monitoring results
      in differences in the incidence of postoperative residual curarization, the use
      of antagonist agents, and the endotracheal extubation rate and outcome after
      continuous infusion of rocuronium in patients undergoing off-pump coronary artery
      bypass surgery. METHODS: Twenty patients were assigned to group 1 (n = 10, non
      blinded neuromuscular transmission monitoring) or group 2 (n = 10, blinded
      neuromuscular transmission monitoring). In group 1, patients were given
      rocuronium at an infusion rate of 6 microg kg(-1) min(-1). The rate was manually
      adjusted in order to maintain T1/T0 at 10%. In group 2, a rocuronium infusion was
      started 30 min after induction of anaesthesia, at a rate of 6 microg kg(-1) min(
      1); this rate was left unchanged during surgery. The rocuronium infusion was
      discontinued on completion of all vascular anastomoses; propofol was stopped at
      the beginning of closure of the subcutis and pirinitramide (piritramide) 15 mg
      was administered intravenously. Remifentanil was discontinued at the beginning of
      skin closure and neostigmine (50 microg kg(-1)) administered at the end of
      surgery when the train-of-four ratio was < 0.9 in group 1, and routinely in group
      2. A 20 min test period for spontaneous ventilation was allowed once surgery had
      been accomplished. When the train-of-four ratio was > or = 0.9 (group 1),
      patients were extubated if also breathing spontaneously, fully awake and able to
      follow commands. When they met the clinical criteria for normal neuromuscular
      function after induced blockade, patients in group 2 were extubated when fully
      awake and able to follow commands. RESULTS: In group 1, the rate of rocuronium
      infusion required to keep T1/T0 at 10% was 5 +/- 1.9 microg kg(-1) min(-1); this
      was not significantly different from the fixed rate in group 2 (P = 0.15). One
      patient in group 2 was excluded. Eight out of 10 and eight out of nine patients
      in groups 1 and 2, respectively, reached the extubation criteria. Three out of
      eight, and five out of eight, patients from groups 1 and 2, respectively, were
      extubated in the operating room. At that time of endotracheal extubation, all
      three patients from group 1, but only four of the five patients from group 2 had
      a train-of-four ratio > or = 0.9. In group 2, one patient was reintubated in the
      intensive care unit. The incidence of pharmacological reversal was high in group
      1. CONCLUSIONS: Although we found no additional benefit of using neuromuscular
      transmission monitoring, it seems an absolute necessity for safety reasons.
      Pharmacological antagonism was mandatory. However, in our opinion, it is not wise
      routinely to perform immediate postoperative extubation in off-pump coronary
      artery bypass surgery.

PMID- 14649341
TI  - Intraperitoneal application of bupivacaine plus morphine for pain relief after
      laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVE: Intraperitoneal administration of a local anaesthetic
      in combination with an opioid, for the relief of postoperative pain, has already
      been reported except after laparoscopic cholecystectomy. This study was aimed at
      assessing the analgesic effect of the intraperitoneal administration of
      bupivacaine and morphine in patients undergoing laparoscopic cholecystectomy.
      METHODS: At the end of laparoscopic cholecystectomy, in a double-blind,
      randomized manner, one of the following injections was given intraperitoneally.
      There were 30 patients in each group: Group 1, physiological saline 30 mL; Group
      2, bupivacaine 0.25% 30 mL; Group 3, bupivacaine 0.25% 30 mL plus morphine 2 mg.
      In addition, Group 2 received 2 mg intravenous (i.v.) morphine in 2 mL saline,
      and Groups 1 and 3, 2 mL saline intravenously. Patients' postoperative pain was
      evaluated using a visual analogue scale and a verbal rating score. The
      postoperative analgesic requirement was assessed by the total dose of metamizol
      administered by an i.v. patient-controlled analgesia (PCA) device. Pain, vital
      signs, supplemental analgesic consumption and side-effects were recorded for all
      patients for 24 h. RESULTS: There were no differences between the three groups
      regarding pain scores (at rest and coughing) during the study except in the first
      2 h, when scores were lower for patients receiving intraperitoneal bupivacaine
      plus i.v. morphine (P < 0.05). Supplemental consumption of metamizol was
      significantly lower (P < 0.05) in Group 3 than in Group 1 during the first 6 h
      after surgery. However, the cumulative doses of metamizol were also lower in
      Group 2 than in Groups 1 and 3 over the entire study (2025 +/- 1044 mg vs. 4925
      +/- 1238 and 4125 +/- 1276mg; P < 0.05). CONCLUSIONS: In patients undergoing
      laparoscopic cholecystectomy, the intraperitoneal administration of morphine plus
      bupivacaine 0.25% reduced the analgesic requirements during the first 6
      postoperative hours compared with the control group. However, the combination of
      intraperitoneal bupivacaine 0.25% and i.v. morphine was more effective for
      treatment of pain after laparoscopic cholecystectomy.

PMID- 14649342
TI  - Nerve-stimulator guided paravertebral blockade vs. general anaesthesia for breast
      surgery: a prospective randomized trial.
AB  - BACKGROUND AND OBJECTIVE: Different anaesthetic techniques are used during breast
      surgery but are frequently associated with unsatisfactory postoperative
      analgesia. Paravertebral nerve blockade has recently been proposed as a
      favourable alternative for this type of surgical procedure, providing excellent
      pain relief and a reduced incidence of postoperative nausea and vomiting. The aim
      of the present study was to compare the use of a nerve-stimulator guided
      paravertebral nerve blockade technique to regular general anaesthesia for breast
      surgery. METHODS: Sixty patients were prospectively randomized to receive either
      paravertebral nerve blockade or general anaesthesia for breast surgery. The
      primary end-point of the study was to assess postoperative analgesia (visual
      analogue scale and supplemental opioid requirements); the incidence of
      postoperative nausea and vomiting and length of hospital stay were considered as
      secondary outcome measures. RESULTS: Visual analogue scores both at rest and at
      movement, as well as the need for supplemental opioid administration during the
      first 3 days postoperatively, were significantly lower in patients handled with
      para-vertebral nerve blockade compared to patients receiving general anaesthesia
      (P < 0.05). The number of patients free from nausea and vomiting after operation
      was significantly higher in the paravertebral nerve blockade group (93%) compared
      to the general anaesthesia group (67%) (P < 0.05). The use of paravertebral nerve
      blockade was also associated with a significantly shorter hospital stay (median 1
      day) compared to general anaesthesia (2 days) (P < 0.01). Both the performance of
      the block and the intraoperative conditions was well accepted by the vast
      majority of patients treated by paravertebral nerve blockade (97%). CONCLUSION:
      The use of paravertebral nerve blockade was associated with improved
      postoperative pain relief, a reduced incidence of nausea and vomiting after
      operation and a shorter duration of hospital stay compared to general anaesthesia
      in patients undergoing breast surgery.

PMID- 14649343
TI  - Improvement in postoperative pain relief by the addition of midazolam to an
      intrathecal injection of buprenorphine and bupivacaine.
AB  - BACKGROUND AND OBJECTIVE: Intrathecal injections of the benzodiazepine midazolam
      have been reported to cause antinociception in animals and pain relief in human
      beings, including the potentiation of opioid analgesia. This study compared the
      efficacy of the addition of midazolam to a mixture of buprenorphine and
      bupivacaine used for spinal anaesthesia. METHODS: The study was prospective,
      randomized, and observer blinded. It involved 60 patients (30 per group), ASA I
      and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery
      under spinal anaesthesia. Patients were randomized into two groups: the control
      group received a spinal injection of hyperbaric bupivacaine (15 mg) plus
      buprenorphine (0.15 mg) and the experimental group received a spinal injection of
      the same two drugs and doses but supplemented with intrathecal midazolam (2 mg).
      RESULTS: The duration of postoperative analgesia in the control group was 9.24 +/
      2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P <
      0.001). Patients treated with intrathecal midazolam had better pain relief judged
      by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P
      < 0.0001). Adverse effects were minor and their incidence was similar in both
      groups. CONCLUSIONS: We conclude that intrathecal midazolam 2 mg improves the
      quality and duration of postoperative pain relief afforded by intrathecal
      buprenorphine and bupivacaine.

PMID- 14649344
TI  - The effect of intrathecal medetomidine on small bowel transit in the rat.
AB  - BACKGROUND AND OBJECTIVE: Gastrointestinal motility is influenced by abdominal
      trauma, laparotomy and particularly by intestinal ischaemia. The reflex
      inhibition of gastrointestinal motility is mediated mainly by the sympathetic
      nervous system. There are reports on the effects of systemically applied alpha2
      adrenoceptor agonists on gastric emptying and recovery of bowel motility, but the
      effect of spinally applied alpha2-adrenoceptor agonists on intestinal motility
      has not been studied. The aim of this study was to investigate the effects of
      intrathecal medetomidine on gastrointestinal transit in rats after transient
      intestinal ischaemia. METHODS: Forty rats were randomly assigned to four groups
      of 10 each. Intrathecal catheter insertion and laparotomy were performed on each
      rat. Saline (10 microL) was injected intrathecally in Groups A and B.
      Medetomidine (10 microg in 10 microL) was injected intrathecally in Groups C and
      D. Intestinal ischaemia was induced in Groups B and D. Gastrointestinal transit
      was determined by measuring the length that a standardized marker meal of
      activated charcoal had travelled. Intrathecal medetomidine was compared to
      intrathecal saline in their effect on intestinal motility after 30 min period of
      bowel ischaemia. RESULTS: Laparotomy and intestinal ischaemia slowed
      gastrointestinal transit. Intrathecal medetomidine accelerated transit in both
      ischaemia and non-ischaemia groups. CONCLUSION: Intrathecal medetomidine markedly
      accelerated small intestinal transit and may also hasten the recovery from post
      ischaemic paralytic ileus.

PMID- 14649345
TI  - Perioperative intravenous adenosine infusion to extend postoperative analgesia in
      brachial plexus block.
AB  - BACKGROUND AND OBJECTIVE: Adenosine infusions have been shown to reduce
      requirements of anaesthetics, to decrease the need for postoperative analgesics
      and to attenuate hyperaesthesia related to neuropathic pain. We decided to
      investigate the effects, beneficial or otherwise, of an adenosine infusion
      administered during surgery. A brachial plexus block was used to produce
      anaesthesia for the surgery. METHODS: Sixty adults undergoing upper extremity
      surgery were included in the study. Brachial plexus block was performed via an
      axillary approach with lidocaine 1.25% and epinephrine 1/200 000 (40 mL).
      Patients were randomly assigned to two groups. During surgery, saline (control)
      or adenosine 80 microg kg min was infused intravenously in a double-blind fashion
      for 1 h. Visual analogue scores every 4 h, analgesic consumption, time to first
      spontaneous pain sensation, time to first rescue analgesic and adverse effects
      were noted during the first 24 h. RESULTS: Vital signs were stable in both groups
      throughout surgery. During the adenosine infusion, one patient fainted while
      another complained of palpitations and tightness of the chest; both patients were
      excluded from further analyses. The time to first sensation of pain was
      significantly longer in the adenosine group compared to the control group (438 +/
      387 vs. 290 +/- 227 min, P = 0.02). The time to first rescue analgesic, the
      visual analogue scale scores and analgesic consumption in the postoperative
      period were similar. CONCLUSIONS: In patients undergoing surgery with an axillary
      plexus block, a perioperative adenosine infusion prolongs the duration of
      postoperative analgesia to some extent. However, the time to first rescue
      analgesic, total analgesic requirements and pain scores were unchanged; the risk
      of potentially serious adverse effects is high. This therapy cannot be
      recommended.

PMID- 14649346
TI  - Efficacy of tramadol versus meperidine for pain relief and safe recovery after
      adenotonsillectomy.
AB  - BACKGROUND AND OBJECTIVE: Adequate relief of pain after tonsillectomy is a common
      problem. We compared meperidine and tramadol when given at induction of
      anaesthesia with respect to their effects on postoperative pain relief and
      emergence characteristics after adenotonsillectomy in children. METHODS: Fifty
      children aged 4-7 yr undergoing tonsillectomy were randomly assigned to receive
      either tramadol 1 mg kg(-1) (n = 25) or meperidine 1 mg kg(-1) (n = 25) before
      commencement of the surgical procedure. Anaesthesia was induced with propofol
      (with cis-atracurium for muscle relaxation) and maintained with sevoflurane in
      oxygen and nitrous oxide. Postoperative pain was scored by a blinded observer
      using a facial pain scale in the recovery room at 0 (at arrival of the patient in
      the postoperative care unit) and at 10, 20 and 45 min thereafter. Agitation
      scores were also assessed by the same observer at 0 min. Heart rate and mean
      arterial pressure were recorded at regular intervals. The time to recovery to
      spontaneous respiration and the incidence of postoperative nausea and vomiting
      were noted. RESULTS: Facial pain scale scores were increased in the tramadol
      group at 0, 10 and 20 min (P < 0.05). No difference was observed in scores at the
      45th min postoperation. Agitation scores were higher in the tramadol group than
      in the meperidine group. No statistical difference was found between the two
      groups. Heart rates and mean arterial pressures were similar in both groups. The
      time to recovery to spontaneous respiration was delayed with meperidine compared
      with tramadol (P < 0.05). The incidence of nausea and vomiting was not
      statistically different between groups. CONCLUSIONS: Meperidine was more
      effective for pain relief and provides better emergence characteristics than
      tramadol after tonsillectomy in children.

PMID- 14649347
TI  - Total intravenous anaesthesia with ketamine-midazolam versus halothane-nitrous
      oxide-oxygen anaesthesia for prolonged abdominal surgery.
AB  - BACKGROUND AND OBJECTIVE: Total intravenous anaesthesia (TIVA) with ketamine
      midazolam (KM) can be used for prolonged abdominal surgery. We compared this
      technique with halothane-nitrous oxide-oxygen anaesthesia using haemodynamic and
      endocrine stress responses as primary outcomes and adequacy of operating
      conditions and recovery profile as secondary outcomes. METHODS: Fifty adult
      patients undergoing radical cystectomy and bladder substitution were randomly
      assigned to receive either TIVA with KM (n = 25) or halothane, nitrous oxide and
      oxygen anaesthesia (n = 25). Invasive haemodynamic and oxygenation variables were
      monitored along with plasma cortisol and growth hormone concentrations. Operative
      conditions and recovery profiles were registered. RESULTS: Cardiac index and
      vascular resistance remained stable during and after surgery. Cortisol
      concentrations doubled during surgery and remained elevated in the recovery
      period. Growth hormone increased after induction, peaked during surgery and
      decreased during recovery. Neither the haemodynamic variables nor the plasma
      hormone concentrations differed significantly between the two groups. Intestinal
      loops were collapsed in the KM groups providing better operative conditions and a
      reduced need for postoperative analgesics. CONCLUSIONS: The stress responses
      during KM anaesthesia for prolonged abdominal surgery were comparable to those
      during halothane-nitrous oxide-oxygen anaesthesia. However, KM anaesthesia
      provided better surgical conditions and better recovery.

PMID- 14649348
TI  - Breathing pattern and workload during automatic tube compensation, pressure
      support and T-piece trials in weaning patients.

PMID- 14649349
TI  - Pre-emptive analgesia produced by interscalene blockade. What failed: the block
      or the methods?

PMID- 14649350
TI  - Recollection of dreams after short general anaesthesia: influence on patient
      anxiety and satisfaction.

PMID- 14649351
TI  - The use of an airway exchange catheter in the management of acute airway
      obstruction.

PMID- 14649352
TI  - Clinical evidence: an avenue to evidence-based medicine.

PMID- 14649353
TI  - Evaluation of in vitro properties of di-tri-octahedral smectite on clostridial
      toxins and growth.
AB  - REASONS FOR PERFORMING STUDY: Clostridial colitis and endotoxaemia of intestinal
      origin are significant causes of morbidity and mortality in horses. Intestinal
      adsorbents are available for treatment of these conditions; however, little
      information exists supporting their use. OBJECTIVES: To evaluate the ability of
      di-tri-octahedral smectite to bind to Clostridium difficile toxins A and B, C.
      perfringens enterotoxin and endotoxin, inhibit clostridial growth and the actions
      of metronidazole in vitro. METHODS: Clostridium difficile toxins, C. perfringens
      enterotoxin and endotoxin were mixed with serial dilutions of di-tri-octahedral
      smectite, then tested for the presence of clostridial toxins or endotoxin using
      commercial tests. Serial dilutions of smectite were tested for the ability to
      inhibit growth of C. perfringens in culture broth, and to interfere with the
      effect of metronidazole on growth of C. perfringens in culture broth. RESULTS:
      Clostridium difficile toxins A and B, and C. perfringens enterotoxin were
      completely bound at dilutions of 1:2 to 1:16. Partial binding of C. difficile
      toxins occurred at dilutions up to 1:256 while partial binding of C. perfringens
      enterotoxin occurred up to a dilution of 1:128. Greater than 99% binding of
      endotoxin occurred with dilutions 1:2 to 1:32. No inhibition of growth of C.
      difficile or C. perfringens was present at any dilution, and there was no effect
      on the action of metronidazole. CONCLUSIONS: Di-tri-octahedral smectite possesses
      the ability to bind C. difficile toxins A and B, C. perfringens enterotoxin and
      endotoxin in vivo while having no effect on bacterial growth or the action of
      metronidazole. POTENTIAL RELEVANCE: In vivo studies are required to determine
      whether di-tri-octahedral smectite might be a useful adjunctive treatment of
      clostridial colitis and endotoxaemia in horses.

PMID- 14649354
TI  - Evaluation of Carolina Rinse solution as a treatment for ischaemia reperfusion of
      the equine jejunum.
AB  - REASONS FOR PERFORMING STUDY: Ileus and peritoneal adhesions are the most common
      complications following surgery for small intestinal obstruction. Carolina Rinse
      (CR) has been shown to decrease reperfusion injury in intestine and other organs.
      HYPOTHESIS: CR decreases intestinal inflammation and subsequent scarring
      associated with reperfusion injury. METHODS: CR was infused intra-arterially and
      applied topically just prior to reperfusion in jejunum exposed to experimental
      ischemia. Vascular permeability, neutrophil accumulation and serosal scarring
      were compared in treated and untreated intestine. RESULTS: CR maintained a normal
      osmotic reflection coefficient and decreased migration of neutrophils into the
      serosa during reperfusion. After 10 days, treated intestine was normal in
      appearance with a trend toward less serosal scarring and fibroblast
      proliferation. There was a significant decrease in fibroplasia at biopsy sites in
      treated intestine. CONCLUSIONS: Arterial perfusion combined with topical
      application of CR during jejunal ischaemia decreases immediate reperfusion injury
      and limits post operative scarring. POTENTIAL RELEVANCE: CR should be used as a
      local perfusate rather than a systemic treatment; it may best be applied
      topically and intraluminally to avoid damaging mesenteric arteries. CR should be
      considered an adjunct treatment as part of overall surgical management and post
      operative care.

PMID- 14649355
TI  - Ultrasonography of the equine cervical region: a descriptive study in eight
      horses.
AB  - REASONS FOR PERFORMING STUDY: In equine patients, the cause of clinical signs
      possibly related to the cervical region is often difficult to diagnose.
      Ultrasonography allows quick and noninvasive visualisation, but reference
      material of the normal equine neck is needed. OBJECTIVES: To describe and
      document the normal ultrasonographic appearance of transverse scans in the
      cervical region with emphasis on the synovial articular facet joints, cervical
      vertebrae and paravertebral structures; and further, to provide images of frozen
      cross-sections for anatomical reference. METHODS: A study describing the normal
      ultrasonographic appearance of the cervical anatomy was performed. Transverse
      scans were obtained from second cervical vertebra (C2) to first thoracic vertebra
      (T1). Post mortem photographs of frozen cross-sections were obtained as
      anatomical reference. RESULTS: The structures were clearly visualised by
      ultrasonography and consistency was found between ultrasonographic images and
      corresponding cross-sectional anatomy. The articular facets varied between horses
      and facets (C2 to T1). Discrepancy in the existing anatomical descriptions was
      found. CONCLUSIONS AND POTENTIAL RELEVANCE: The anatomical and ultrasonographic
      description provides a reference for ultrasonographic evaluation of equine
      cervical facet joints, vertebrae and paravertebral structures. The findings and
      variations found are considered to reflect the naturally occurring variations in
      horses.

PMID- 14649356
TI  - Accuracy of ultrasound-guided intra-articular injection of cervical facet joints
      in horses: a cadaveric study.
AB  - REASONS FOR PERFORMING STUDY: Intra-articular facet joint injection is an
      established diagnostic procedure in human medicine but there are no reports on
      its reliability in equine practice. OBJECTIVES: To investigate the accuracy of
      ultrasound-guided intra-articular injections of the cervical facet joints and to
      estimate factors influencing the accuracy. METHODS: Sixty injections with blue
      dye were performed on the facet joints between 2nd and 7th cervical vertebra (C2
      C7) on horses subjected to euthanasia for nonorthopaedic reasons. The facet
      joints were subsequently dissected to verify accuracy of deposition. RESULTS:
      Seventy-two percent of the injections were found to be intra-articular, 17% were
      intracapsular and a total of 98% were within 1 mm of the joint capsule. There was
      a marked effect of gained experience (P < 0.01), but not of other factors tested.
      CONCLUSIONS AND POTENTIAL RELEVANCE: The results of the present study do not
      translate directly to injections performed in live horses, but they indicate that
      the method can be applied as a diagnostic as well as therapeutic procedure in C2
      to C7 and that is advisable to practise injections on cadaver specimens before
      applying the technique.

PMID- 14649357
TI  - Retrospective study of 24 cases of septic calcaneal bursitis in the horse.
AB  - REASONS FOR PERFORMING STUDY: Wounds to the plantar aspect of the tarsus present
      a diagnostic and treatment challenge. This study was undertaken to describe
      specific features of traumatic wounds involving the calcaneal bursa, with a view
      to determining which clinical examination findings and diagnostic tests results
      could provide reliable indicators of prognosis. OBJECTIVES: To report clinical
      presentation, diagnostic findings, treatment and outcome of 24 cases of septic
      calcaneal bursitis; and to determine the importance of the involvement of
      specific anatomical structures in relation to the prognosis for survival and
      return to athletic function. METHODS: Records of 24 horses that had suffered
      traumatic wounds involving the calcaneal bursae were reviewed and divided into 3
      groups, based on the bursa involved and presence or absence of involvement of the
      tuber calcanei. Clinical, diagnostic imaging and surgical findings were recorded
      for each case. Differences between groups and outcome were examined for
      significance with Chi-squared, Fisher's Exact or Kruskal-Wallis tests, as
      appropriate. RESULTS: Wounds involving only the subcutaneous bursa had an
      excellent prognosis for survival. Seventy-five percent of horses with wounds
      involving the intertendinous calcaneal bursa survived. Involvement of the tuber
      calcanei presented a fair to guarded prognosis, with only 44% of horses with
      involvement of this structure surviving. CONCLUSIONS: In contrast to other
      studies of septic synovial structures, the time between initial injury and
      referral did not affect the outcome. Correct identification of invasion of the
      calcaneal bursa(e) and/or tuber calcanei in wounds to the plantar aspect of the
      tarsus allows for more accurate pronostication. Damage to the tuber calcanei
      presents a poorer prognosis than for cases that involve only the soft tissue
      structures in the region. POTENTIAL RELEVANCE: This study demonstrates the
      importance of correct anatomical identification of structures involved in wounds
      in the region of the calcaneal bursa. The use of radiography, ultrasonography and
      synoviocentesis are essential in these cases to provide the most appropriate
      treatment for the horse and accurate prognosis for the owner.

PMID- 14649358
TI  - Results of plate fixation of type 1b olecranon fractures in 24 horses.
AB  - REASONS FOR PERFORMING STUDY: Previous olecranon fracture reports contain a small
      proportion of type 1b fractures, with only a few repaired by tension band plate
      fixation. OBJECTIVES: To evaluate subject details, history, clinical findings and
      outcome of type 1b olecranon fractures in a large group of horses treated by
      tension band plate fixation. METHODS: Medical records of 77 horses diagnosed with
      an olecranon fracture were reviewed. Twenty-four horses (31%) were classified as
      having type 1b olecranon fractures. Clinical details and follow-up results (4-128
      months post operatively) were recorded. RESULTS: Treatment included open
      reduction and internal fixation using a narrow dynamic compression plate (n =
      20), conservative therapy (n = 2) and euthanasia (n = 2). Long-term follow-up was
      available for 16 plated horses. Four were sound and in training and 9 were sound
      and performing athletically. Articular surface involvement, comminution, open
      status or removal of anconeal process fragments did not appear to affect
      prognosis or soundness. CONCLUSIONS: Internal plate fixation provides an
      excellent prognosis for an animal capable of athletic performance. POTENTIAL
      RELEVANCE: Describing tension band plate fixation and results offers a method of
      fracture repair that will improve the treatment and prognosis for type 1b
      olecranon fractures.

PMID- 14649359
TI  - Effect of controlled exercise on middle gluteal muscle fibre composition in
      Thoroughbred foals.
AB  - REASONS FOR PERFORMING STUDY: Most racehorses are trained regularly from about
      age 18 months; therefore, little information is available on the effect of
      training in Thoroughbred foals. HYPOTHESIS: Well-controlled exercise could
      improve muscle potential ability for endurance running. METHODS: Thoroughbred
      foals at age 2 months were separated into control and training (treadmill
      exercise) groups and samples obtained from the middle gluteal muscle at 2 and 12
      months post partum. Muscle fibre compositions were determined by histochemical
      and electrophoretical techniques and succinic dehydrogenase (SDH) activity was
      analysed in each fibre type. RESULTS: All fibre types were hypertrophied with
      growth and type I and IIA fibres were significantly larger in the training than
      the control group at age 12 months. A significant increase of SDH activity was
      found in type IIX muscle fibres in the training group. CONCLUSIONS: Training in
      young Thoroughbred horses can facilitate muscle fibre hypertrophy and increase
      the oxidative capacity of type IIX fibres, which could potentially enhance
      stamina at high speeds. POTENTIAL RELEVANCE: To apply this result to practical
      training, further studies are needed to determine more effective and safe
      intensities of controlled exercise.

PMID- 14649360
TI  - Lameness in 46 horses associated with deep digital flexor tendonitis in the
      digit: diagnosis confirmed with magnetic resonance imaging.
AB  - REASONS FOR PERFORMING STUDY: The differential diagnosis of foot pain has long
      proved difficult and the use of magnetic resonance imaging (MRI) offers the
      opportunity to further the clinical understanding of the subject. OBJECTIVES: To
      determine the incidence of deep digital flexor tendon (DDFT) injuries in a series
      of 75 horses with lameness associated with pain localised to the digit, with no
      significant detectable radiographic or ultrasonographic abnormalities, using MRI;
      and to describe a variety of lesion types and relate DDF tendonitis with
      anamnesis, clinical features, response to local analgesic techniques and nuclear
      scintigraphic and ultrasonographic findings. METHODS: All horses undergoing MRI
      of the front feet between January 2001 and October 2002 were reviewed and those
      with DDFT injuries categorised according to lesion type; horses with primary
      tendonitis (Group I) and those with concurrent abnormalities of the navicular
      bone considered to be an important component of the lameness (Group II). The
      response to perineural analgesia of the palmar digital nerves and palmar (abaxial
      sesamoid) nerves, intra-articular analgesia of the distal interphalangeal (DIP)
      joint and analgesia of the navicular bursa were reviewed. The result of
      ultrasonography of the pastern and foot was recorded. Lateral, dorsal and solar
      pool and bone phase nuclear scintigraphic images were assessed subjectively and
      objectively using region of interest (ROI) analysis. RESULTS: Forty-six (61%) of
      75 horses examined using MRI had lesions of the DDFT considered to be a major
      contributor to lameness. Thirty-two horses (43%) had primary DDFT injuries and 14
      (19%) a combination of DDF tendonitis and navicular bone pathology. Lesions
      involved the insertional region of the tendon alone (n = 3), were proximal to the
      navicular bone (n = 23) or were at a combination of sites (n = 20). Lesion types
      included core lesions, focal and diffuse dorsal border lesions, sagittal plane
      splits, insertional injuries and lesions combined with other soft tissue
      injuries. Many horses had a combination of lesion types. Lameness was abolished
      by palmar digital analgesia in only 11 of 46 horses (24%). Twenty-one of 31
      horses (68%) in Group I showed > 50% improvement in lameness after intra
      articular analgesia of the DIP joint, whereas 11 of 12 horses (92%) in Group II
      had a positive response. Twelve of 18 horses (67%) in Group I had a positive
      response to analgesia of the navicular bursa. Nineteen horses had lesions of the
      DDFT extending proximal to the proximal interphalangeal joint seen using MRI, but
      these were identified ultrasonographically in only 2 horses. Scintigraphic
      abnormalities suggestive of DDFT injury were seen in 16 of 41 horses (41%), 8 in
      pool phase images and 8 in bone phase images. CONCLUSIONS AND POTENTIAL
      RELEVANCE: DDFT injuries are an important cause of lameness associated with pain
      arising from the digit in horses without detectable radiographic abnormalities.
      Lameness is not reliably improved by palmar digital analgesia, but may be
      improved by intra-articular analgesia of the DIP joint in at least 68% of horses.
      Ultrasonography is not sensitive in detecting lesions of the DDFT in the distal
      pastern region, but a combination of pool and bone phase scintigraphic images of
      the digit is helpful in some horses. Further follow-up information is required to
      determine the prognosis for horses with lesions of the DDFT in the digit and to
      establish whether this is related to lesion severity and/or location.

PMID- 14649361
TI  - Effect of GastroGard and three compounded oral omeprazole preparations on 24 h
      intragastric pH in gastrically cannulated mature horses.
AB  - REASONS FOR PERFORMING STUDY: Ulceration of the squamous gastric mucosa is
      commonly associated with intensive training programmes in horses, but only one
      compound ('Gastrogard') has been subjected to controlled scrutiny as to
      therapeutic efficacy. OBJECTIVES: To compare the gastric acid inhibitory efficacy
      of one manufactured ('GastroGard') and 3 generic pharmacy-compounded preparations
      of the proton pump inhibitor omeprazole (OME) in the mature horse. HYPOTHESIS:
      All OME preparations tested would induce a clinically acceptable effect. METHODS:
      Six healthy mature gastrically cannulated horses of various breeds, 3 mares and 3
      geldings, were used. Each product was administered per os once daily (0730 h) at
      an equivalent dose of 4 mg OME/kg bwt, in a randomised complete repeated measures
      design for sequence of individual preparation treatment per horse. There was a
      minimum of 14 days between treatment regimens. A portable unit that recorded pH
      continuously was attached to a recording electrode fixed within the gastric lumen
      via the gastric cannula. Three 24 h recordings were made one day before and
      during Days 2 and 7 after commencement of a 7 day treatment with each of the 4
      individual preparations. The horses were fed as usual throughout the study.
      RESULTS: Only the GastroGard and one other preparation induced a significant
      increase over baseline in mean percentage of time that the pH was > 4.0 and mean
      median intragastric pH, during the first 14 and 12 h post treatment respectively,
      for both Days 2 and 7 post treatment. Both these products had a vehicle pH > 8.0,
      in contrast to the 2 less effective products, where the vehicle pH was < 6.0.
      CONCLUSIONS: OME at 4 mg/kg per os s.i.d. can effectively maintain intragastric
      pH at an accepted anti-ulcerogenic level for at least 12 h post administration in
      mature horses. In contrast to GastroGard, it should not be expected that all
      compounded preparations of OME are equally effective in achieving this
      performance. It appears that vehicle pH might play an important part in
      determining preparation efficacy. POTENTIAL RELEVANCE: Optimal timing for daily
      dosing of athletic horses with an effective OME preparation, in order to suppress
      gastric squamous ulceration, might be 4-8 h prior to a training session.

PMID- 14649362
TI  - Quantification and age-related distribution of articular cartilage degeneration
      in the equine fetlock joint.
AB  - REASONS FOR PERFORMING STUDY: The equine fetlock joint has the largest number of
      traumatic and degenerative lesions of all joints of the appendicular skeleton.
      OBJECTIVE: To gain insight into the distribution of cartilage degeneration across
      the articular surface in relation to age in order better to understand the
      dynamic nature and progression of osteoarthritis (OA). HYPOTHESIS: That there
      would be a specific age-related distribution pattern of cartilage degeneration in
      the equine metacarpophalangeal joint. METHODS: The proximal articular cartilage
      surfaces of the first phalanges (P1) of 73 slaughter horses (age range 0.4-23
      years) with different stages of osteoarthritis were scored semiquantitatively on
      a 0 to 5 scale and also assessed quantitatively using the cartilage degeneration
      index (CDI(P1)), which ranges from 0 to 100%. Furthermore, CDI values were
      determined for special areas of interest; medial dorsal surface (CDI(mds)),
      lateral dorsal surface (CDI(lds)), medial central fovea (CDI(mcf)) and lateral
      central fovea (CDI(lcf)). Correlations were calculated for CDI(P1) values and CDI
      values at the specific areas of interest with macroscopic scores and with age.
      RESULTS: There was a high correlation between the semiquantitative macroscopic
      score and the quantitative CDI(P1) values (r = 0.92; P < 0.001). A macroscopic
      score of 0 (i.e. no obvious cartilage degeneration) corresponded with a CDI(P1)
      mean +/- s.e. value of 25 +/- 2.8% and a macroscopic score of 5 (i.e. severe
      cartilage degeneration in localised areas) with a mean +/- s.e. value of 38.1 +/-
      7.9%. There was a moderate but highly significant correlation between the CDI(P1)
      value and the age of the horses (r = 0.41; P < 0.001). Highest CDI values were
      calculated for the medial dorsal surface (from 10.6 +/- 2.8% at macroscopic Grade
      0 to 63.1 +/- 8.4% at Grade 5). At the lateral dorsal surface, these values were
      5.9 +/- 1.4% and 47.2 +/- 10.4%, respectively. The CDI(mcf) and CDI(lcf) were
      significantly lower (P < 0.05) than the CDI(mds) and CDI(lds) at all grades. The
      CDI(mcf) ranged from 1.0 +/- 2.9% at Grade 0 to 43.7 +/- 9.1% at Grade 5;
      laterally, these values were 1.5 +/- 2.6% and 15.2 +/- 6.2%, respectively.
      CONCLUSIONS: CDI grading increased from lateral to medial and from central to
      dorsal. This specific distribution pattern confirms the heterogeneous nature of
      the OA process and strongly supports an important role for biomechanical loading,
      superimposed on age-related changes, in the spread of the disorder over the
      joint. POTENTIAL RELEVANCE: Knowledge of the development of OA across the
      articular surface is essential for understanding the dynamic nature and
      progression of the disease and can form a basis for improvements in diagnostic
      and therapeutic approaches to degenerative joint disease.

PMID- 14649363
TI  - Gender differences in bone turnover in 2-year-old Thoroughbreds.
AB  - REASONS FOR PERFORMING STUDY: Injuries to the skeleton are a major cause of
      morbidity and mortality in racehorses and age, gender and season have all been
      shown to influence risk of injury. OBJECTIVES: To use biochemical markers of bone
      cell activity to establish to whether cellular processes in bone underlie these
      described effects. METHODS: Blood samples were collected monthly from 2-year-old
      horses in race training between November 1998 and September 1999. Mean age at the
      start of the study was 20 months (range 18-23 months), with no significant
      difference in average age between colts (n = 84) and fillies (n = 63). Three
      markers were measured; osteocalcin (OC, bone formation), the carboxyterminal
      cross-linked telopeptide of type I collagen (ICTP, bone resorption) and the
      carboxyterminal propeptide of type I collagen (PICP), which is less 'bone
      specific' than the other 2 markers. RESULTS: Colts had, on average, 3.62 ng/ml
      higher OC concentrations (P = 0.044) and 0.68 mg/l higher ICTP concentrations (P
      = 0.01) than fillies. The effect of gender was not statistically significant for
      PICP. However, in May, PICP concentrations were on average 157 mg/l higher in
      fillies than colts. There was no effect of age or season on marker
      concentrations. CONCLUSIONS: This study has shown that there are gender
      differences in bone turnover markers in 2-year-old Thoroughbreds; however, age,
      within the limited range studied, did not have a significant effect on bone cell
      activity. Lower bone marker concentrations may reflect smaller bone size and/or
      earlier skeletal maturation in fillies. An increase in concentrations of PICP in
      fillies in spring and early summer may relect an influence of sex hormones on
      collagen turnover. POTENTIAL RELEVANCE: Gender differences in bone cell activity
      in 2-year-old colts and fillies may influence bone's adaptive responses to
      training and risk of injury.

PMID- 14649365
TI  - Third metacarpal bone length and skeletal asymmetry in the Thoroughbred
      racehorse.

PMID- 14649364
TI  - The efficacy of dantrolene sodium in controlling exertional rhabdomyolysis in the
      Thoroughbred racehorse.
AB  - REASONS FOR PERFORMING STUDY: Dantrolene sodium (Dantrium) has been used
      extensively for the treatment of myopathies in man and anecdotal evidence
      suggests it is of clinical benefit in the control of exercise-induced
      rhabdomyolysis (ER) in racehorses, although data to support this are currently
      lacking. OBJECTIVES: To investigate the efficacy of oral dantrolene sodium in
      controlling ER in a randomised, double-blind, placebo-controlled crossover trial
      involving 77 Thoroughbred racehorses in Newmarket, UK. METHODS: Horses were
      treated on 2 occasions 1 week apart, with treatment days coinciding with a return
      to exercise following 2 days box rest on each occasion. For the first treatment,
      each horse was randomly selected to receive either 800 mg dantrolene sodium or a
      colour-matched placebo administered orally 1 h before exercise. This was followed
      by crossover to the other treatment on the second occasion, with each horse
      thereby acting as its own control. Degree of ER was assessed using rising serum
      creatine kinase (CK) levels, by subtracting pre-exercise blood CK levels from
      those measured in 6 h post exercise blood samples. For each horse, the difference
      in change between pre- and post exercise CK values between placebo and dantrolene
      treatments was calculated, with positive values indicating a greater rise with
      placebo than with dantrolene sodium treatment. RESULTS: The overall mean
      difference for all horses was +104.8 iu/l and the null hypothesis, that there was
      no true difference in non-normally distributed post exercise rises in CK values
      between placebo and dantrolene treatments, was rejected (P = 0.0013) using the
      nonparametric Wilcoxon signed rank test. Additionally, no horses given dantrolene
      sodium showed clinical signs of ER, whereas 3 horses given the placebo developed
      ER following exercise. The incidence of ER in the study was 4% (3/77).
      CONCLUSIONS: The results confirmed that oral administration of dantrolene sodium,
      1 h before exercise, had a statistically significant effect on reducing the
      difference between pre- and post exercise plasma CK levels compared with a
      placebo in the same animals, and preventing clinical ER in susceptible
      individuals. POTENTIAL RELEVANCE: This study suggested that dantrolene sodium is
      of use in controlling ER in the Thoroughbred racehorse. Further investigation
      into pre- and post exercise myoplasmic calcium levels and the repeat of the study
      late in the season when horses receive a much higher energy ration and more
      strenuous exercise would appear to be warranted.

PMID- 14649366
TI  - Long-term control of mucocutaneous squamous cell carcinoma and metastases in a
      horse using piroxicam.

PMID- 14649367
TI  - Jejunal perforation in three young horses.

PMID- 14649368
TI  - Antemortem diagnosis of equine mesothelioma by pleural biopsy.

PMID- 14649369
TI  - Fast foods, energy density and obesity: a possible mechanistic link.
AB  - Fast foods are frequently linked to the epidemic of obesity, but there has been
      very little scientific appraisal of a possible causal role. Here we review a
      series of studies demonstrating that the energy density of foods is a key
      determinant of energy intake. These studies show that humans have a weak innate
      ability to recognise foods with a high energy density and to appropriately down
      regulate the bulk of food eaten in order to maintain energy balance. This induces
      so called 'passive over-consumption'. Composition data from leading fast food
      company websites are then used to illustrate that most fast foods have an
      extremely high energy density. At some typical outlets the average energy density
      of the entire menus is approximately 1100 kJ 100 g(-1). This is 65% higher than
      the average British diet (approximately 670 kJ 100 g(-1)) and more than twice the
      energy density of recommended healthy diets (approximately 525 kJ 100 g(-1)). It
      is 145% higher than traditional African diets (approximately 450 kJ 100 g(-1))
      that probably represent the levels against which human weight regulatory
      mechanisms have evolved. We conclude that the high energy densities of many fast
      foods challenge human appetite control systems with conditions for which they
      were never designed. Among regular consumers they are likely to result in the
      accidental consumption of excess energy and hence to promote weight gain and
      obesity.

PMID- 14649370
TI  - Prevalence of overweight among children in Europe.
AB  - Estimates of the prevalence of childhood overweight and obesity have been made in
      several European countries during the last decade. The methods used and the
      assessment criteria differ from survey to survey. The present paper reports the
      prevalence data from 21 surveys in Europe using a single, internationally
      accepted definition of overweight in childhood, allowing direct comparisons to be
      made. A tendency for a higher prevalence of overweight among children in western
      and especially southern Europe is shown and some possible reasons for this are
      discussed.

PMID- 14649371
TI  - Liquid calories and the failure of satiety: how good is the evidence?
AB  - Increasing rates of obesity and overweight have been attributed to the growing
      proportion of dietary energy that is consumed in liquid form. Liquids reportedly
      fail to trigger physiological satiety mechanisms so that compensation for energy
      consumed as beverages may be imprecise and incomplete. Sweetened beverages have
      come under particular scrutiny, as their consumption exceeds that of milk and
      fruit and vegetable juices. However, the evidence that liquids have less impact
      on satiety than do solid foods remains inconclusive. Some published studies have
      reported that liquids are less satiating than solids, whereas other studies have
      reported that solids are less satiating than liquids. In laboratory studies, the
      degree of energy compensation following pre-load ingestion was influenced by
      subject characteristics, pre-load volume, or the time lag between the pre-load
      and the next meal. Such factors appear to interact with pre-load texture in their
      impact on hunger and satiety and later food consumption.

PMID- 14649372
TI  - Psychosocial origins of obesity stigma: toward changing a powerful and pervasive
      bias.
AB  - Widespread bias and discrimination based on weight have been documented in key
      areas of living, including education, employment, and health care. This paper
      examines the social and psychological origins of this bias through a review and
      critique of theoretical and empirical literatures, and proposes how the field
      might best advance in the area of reducing stigma. Explanations for the
      development and reduction of weight stigma are examined with different
      theoretical approaches, including attribution theory and a social consensus
      model. Individual and sociocultural contributors to bias suggested by these
      approaches are highlighted. New directions are discussed in both the
      understanding and prevention of weight bias.

PMID- 14649373
TI  - Functional neuroimaging: a new generation of human brain studies in obesity
      research.
AB  - Obesity is predominantly caused by overeating, an abnormal behaviour for which
      there is no unequivocal neurophysiological explanation. Functional neuroimaging
      techniques, such as positron emission tomography (PET) and functional magnetic
      resonance imaging (fMRI), have recently emerged as new tools to search for
      regions of the brain that are involved in the regulation of eating behaviours and
      those that are involved in the pathophysiology of obesity. Using these
      techniques, a limited number of studies have provided the first in vivo images of
      the human hypothalamic response to nutritional stimuli and revealed the
      complexity of the human brain response to hunger, taste, and satiation. Selective
      differences have been reported in the functional architecture of the brain of
      obese and lean individuals. We discuss current use and possible future
      developments of functional neuroimaging applied to obesity research. We conclude
      that functional neuroimaging provides an increasingly important tool for
      investigating how different regions of the brain work in concert to orchestrate
      normal eating behaviours and how they conspire to produce obesity and other
      eating disorders.

PMID- 14649374
TI  - Recent developments in our understanding of melanocortin system in the regulation
      of food intake.
AB  - Obesity has become one of the most significant public health problems facing the
      world today. However, the pathogenesis of obesity is multifactorial and involves
      the interaction of genetic and environmental factors. There is a pressing need to
      better understand the biochemical pathways that control energy intake and
      expenditure. In the last few years, a number of important signalling molecules
      have been identified that play important roles in obesity. One family of these
      molecules is the melanocortin system, which consists of several components: (1)
      melanocortin peptides; (2) the five seven-transmembrane G-protein coupled
      melanocortin receptors (MCRs); (3) the endogenous MCR antagonists, agouti and
      agouti-related protein; (4) the endogenous melanocortin mediators, mahogany, and
      syndecan. This system plays a key role in the central nervous system control of
      feeding behaviour and energy expenditure. This article will provide an overview
      of the anatomy, physiology, and molecular biology of the melanocortin system, and
      recent developments in our understanding of this system in obesity.

PMID- 14649375
TI  - Studies of natural allele effects in mice can be used to identify genes causing
      common human obesity.
AB  - Although genes causing rare Mendelian forms of human obesity have provided much
      useful information about underlying causes of obesity, these genes do not explain
      significant proportions of common obesity. This review presents evidence that
      animal models can be used to uncover subtle genetic effects on obesity and can
      provide a powerful rigorous compliment to human association studies. We discuss
      the advantages of animal models of obesity, various approaches to discovering
      obesity genes, and the future of mapping and isolating naturally occurring
      alleles of obesity genes. We review evidence that it is important to map
      naturally occurring obesity genes using quantitative trait locus (QTL) mapping,
      instead of mutagenesis and knockout models because the latter do not allow study
      of interactions and because naturally occurring obesity alleles can interfere
      with cloning from mutagenesis projects. Because a substantial percentage of human
      obesity results from complex interactions, the underlying genes can only be
      identified by direct studies in humans, which are still very difficult, or by
      studies in mice that begin with QTL mapping. Finally, we emphasize that animal
      model studies can be used to prove that a specific gene, only associated with
      obesity in humans, can indeed be the underlying cause of obesity in mammals.

PMID- 14649376
TI  - Physical inactivity, excess adiposity and premature mortality.
AB  - The purpose of this report is to review the evidence that physical inactivity and
      excess adiposity are related to an increased risk of all-cause mortality, and to
      better identify the independent contributions of each to all-cause mortality
      rates. A variance-based method of meta-analysis was used to summarize the
      relationships from available studies. The summary relative risk of all-cause
      mortality for physical activity from the 55 analyses (31 studies) that included
      an index of adiposity as a covariate was 0.80 [95% confidence interval (CI) 0.78
      0.821, whereas it was 0.82 [95% CI 0.80-0.84] for the 44 analyses (26 studies)
      that did not include an index of adiposity. Thus, physically active individuals
      have a lower risk of mortality by comparison to physically inactive peers,
      independent of level of adiposity. The summary relative risk of all-cause
      mortality for an elevated body mass index (BMI) from the 25 analyses (13 studies)
      that included physical activity as a covariate was 1.23 [95% CI 1.18-1.29], and
      it was 1.24 [95% CI 1.21-1.28] for the 81 analyses (36 studies) that did not
      include physical activity as a covariate. Studies that used a measure of
      adiposity other than the BMI show similar relationships with mortality, and
      stratified analyses indicate that both physical inactivity and adiposity are
      important determinants of mortality risk.

PMID- 14649377
TI  - Embryonic versus adult stem cell pluripotency: in liver only fusion matters.

PMID- 14649378
TI  - Treatment-associated serum FSH levels in very poor responders to ovarian
      stimulation.
AB  - PURPOSE: To compare treatment-associated follicle-stimulating hormone (FSH)
      response in patients undergoing controlled ovarian hyperstimulation with either
      microdose flare (MDF) leuprolide acetate or clomiphene citrate and human
      menopausal gonadotropin (CC/hMG). METHODS: Thirteen patients who were deemed poor
      responders underwent stimulation with one of two poor responder stimulation
      protocols (MDF group: n = 8; CC/hMG group: n = 5). Serum FSH, estrone (E1),
      estrone sulfate (E1S), and estradiol (E2) levels were measured at baseline, day 5
      of medication, and on day of hCG administration. Ovarian and uterine responses
      were evaluated by ultrasound. RESULTS: Treatment-associated FSH levels were
      consistently higher in the group that took CC/hMG. However, serum E1, E1S, and E2
      values were similar in both groups as were the number of oocytes retrieved and
      the endometrial echo complex. There were no differences between the two groups
      with regards to the quality of the oocytes obtained, fertilization rate, or the
      quality of the embryos. CONCLUSION: Clomiphene citrate, when administered in
      conjunction with exogenous hMG, is a more potent stimulator of FSH production
      than MDF leuprolide acetate among poor responders to ovarian stimulation.
      However, the number of oocytes is not increased.

PMID- 14649379
TI  - Factors associated with an optimal pregnancy outcome in an oocyte donation
      program.
AB  - PURPOSE: To identify donor and recipient variables that may have a significant
      impact on pregnancy outcome in order to optimize results of an oocyte donation
      program. METHOD: Retrospective analysis through a Generalized Estimating Equation
      (GEE) approach to clustered and binary clustered data, linear mixed effects
      model, scatter plot smoothing functions, and receiving operator characteristics
      (ROC) curves. SETTING: University-based center. INTERVENTION(S): None. MAIN
      OUTCOME MEASURES: Pregnancy and implantation rates. PATIENTS: 257 donation and
      transfer cycles. RESULT(S): Overall results were as follows: clinical pregnancy
      rate, 47%; implantation rate, 22%; abortion rate, 19%; and overall multiple
      pregnancy rate, 35%. The total reproductive potential was 60%. Implantation and
      pregnancy rates were not significantly related to any variable from donors or
      recipients. Abortion rate increased significantly with donors' increased basal
      serum LH. Pregnancy rate was significantly enhanced with improved embryo quality.
      In donors stimulated more than once, the pregnancy rate was 84%. CONCLUSION(S):
      Although no single or combined donor or recipient variable(s) could be identified
      as predictor(s) of pregnancy, the data suggest that donors < or = 33 years of age
      with basal cycle day 3 serum levels of FSH 4-8 IU/L, LH < 8 IU/L, and E2 < 70
      pg/mL had an optimal outcome. Transfer of two selected embryos on day 3 yields a
      favorable pregnancy outcome while significantly decreasing the occurrence of
      multiple pregnancies. These policies, in addition to embryo cryopreservation,
      were associated with optimal pregnancy outcome in oocyte donation.

PMID- 14649380
TI  - Comparison of pregnancy, implantation, and multiple gestation rates for day 3
      versus day 5 embryo transfers.
AB  - PURPOSE: To compare pregnancy, implantation, and multiple gestation rates
      resulting from day 3 and day 5 embryo transfers after in vitro fertilization
      emphasizing a subset of patients who met criteria for day 5 transfer but elected
      to undergo day 3 transfer. METHOD: A retrospective analysis of day 3 and day 5
      embryo transfers from January 2001 to June 2002 were evaluated in a community
      teaching hospital setting. A total of 331 patients < or = 40 years old were
      included. Using Student's t test, chi2 test, and Fisher's exact test, we compared
      the pregnancy, implantation, and multiple gestation rates. RESULTS: Pregnancy,
      implantation, and multiple gestation rates were not significantly different
      between the subgroup who met criteria for day 5 embryo transfer but elected day 3
      transfer. There was no significant difference between similar parameters in the
      overall comparison of day 3 versus day 5 embryo transfers. CONCLUSIONS:
      Blastocyst transfers have similar multiple gestation rates, pregnancy rates, and
      implantation rates when compared to day 3 embryo transfers.

PMID- 14649381
TI  - The relationship of pronuclear stage morphology and chromosome status at cleavage
      stage.
AB  - PURPOSE: Infertile couples undergoing in vitro fertilization-embryo transfer (IVF
      ET) program were included to study the relationship of pronuclear stage
      morphology and chromosome status at cleavage stage. METHODS: Eighteen to twenty
      one hours after fertilization, zygotes were checked for pronuclear morphology
      with modified Scott Z-score system. After embryo transfer on day 3, arrested or
      non-transferred 2 PN embryos were spread for fluorescence in situ hybridization
      (FISH) staining of probes to chromosomes 18, X and Y. RESULTS: Ninety-eight
      embryos were successfully fixed and stained. The chromosome status were recorded
      in each 2 PN score group: 7 (54%) of 13 embryos in Z2 group, 14 (35%) of 40 in Z3
      group and 10 (36%) of 28 in Z4 group being normal diploid. Z1 group has 12 (71%)
      of 17 embryos being normal diploid, which is significantly more than Z3 (p =
      0.020) and Z4 group (p = 0.033). CONCLUSION: Our results demonstrated a high
      probability to get normal diploid embryos if good morphology at pronuclear stage
      was used as selection criteria, especially for Z1 score embryos.

PMID- 14649383
TI  - Relationship between human sperm morphology and acrosomal function.
AB  - PURPOSE: In this study, we investigated the relationship between functionality of
      the acrosome and sperm morphology. METHODS: Acrosome reaction (AR) was separately
      determined in live and dead sperm and in those with normal, small, and large
      sized acrosomes by means of the triple stain. Morphology was analyzed according
      to strict criteria after Papanicolaou stain. RESULTS: AR and morphology
      correlated regarding detection of large and small sized acrosomes, but not for
      normal sized acrosomes. Spontaneous AR was significantly influenced by acrosomal
      size. Sperm with large (11.4%) and normal (9.2%) acrosomes exhibited a
      significantly higher percentage of life spontaneously acrosome-reacted sperm than
      those with small acrosomes (4.5%). Sperm with small acrosomes were associated
      with a higher percentage of cell death. CONCLUSION: The results indicate that
      sperm with small acrosomes are more susceptible to cell death and
      nonphysiological acrosomal loss. Acrosome size reflects the physiological
      capability of sperm function and therefore male fertility potential.

PMID- 14649384
TI  - Tubal pregnancy following tubal embryo transfer into the contralateral fallopian
      tube.
AB  - Ectopic and heterotopic pregnancy may occur with increased frequency following
      assisted reproductive technology (ART) procedures. In addition, there may be
      unusual sites of implantation, which may cause atypical and confusing clinical
      manifestations. We present a case of tubal pregnancy after tubal embryo transfer
      (TET) to the contralateral fallopian tube. Four embryos were transferred to the
      left fallopian tube by laparoscopy, but the patient developed a right tubal
      pregnancy, possibly as a result of intrauterine or intra-abdominal migration of
      the embryo. ART patients must be followed closely soon after the procedure, and
      there should be a high index of suspicion for an unusual implantation site.

PMID- 14649382
TI  - Mouse ovarian tissue cryopreservation has only a minor effect on in vitro
      follicular maturation and gene expression.
AB  - PURPOSE: To establish a protocol for ovarian tissue cryopreservation which can
      retain fertility potential after thawing and to evaluate the impact of
      cryopreservation on development and gene expression during folliculogenesis.
      METHODS: A controlled randomized study in a clinical and academic research
      setting in a university medical center was conducted to study cryopreservation
      and in vitro maturation (IVM) of mouse ovarian follicles. Preantral follicles
      isolated from either fresh (Group A) or cryopreserved (Group B) murine ovarian
      tissues were used to test their fertility potential by in vitro culture-in vitro
      maturation (IVC-IVM). Expression of Graafian follicles derived from both groups
      were detected by DNA microarray techniques for comparison. RESULTS: Although
      there were no significant differences in IVM outcomes and follicular gene
      expression between the two experimental groups, cryopreservation appears to
      induce the expression of heat shock proteins, DNA-damage-inducible protein 45 and
      death-related apoptosis genes (i.e., Fas and Fas-ligand). CONCLUSION:
      Cryopreservation may trigger biological events not amenable to normal cell
      function and follicular development. However, neither follicular development nor
      gene expression was dramatically changed after cryopreservation. These data
      suggest that although our current cryopreservation techniques yield competent
      follicles and mature oocytes, subtle changes observed in gene expression imply
      that the present cryopreservation techniques need to be further refined.

PMID- 14649385
TI  - Symptom control in advanced disease: why all the fuss?

PMID- 14649386
TI  - A one year health economic model comparing transdermal fentanyl with sustained
      release morphine in the treatment of chronic noncancer pain.
AB  - A Markov model was constructed to simulate the resource use and health outcomes
      of one year of treatment comparing the fentanyl transdermal therapeutic system
      (fentanyl-TTS) with oral sustained-release (SR) morphine in outpatients with
      noncancer pain in Denmark. Effectiveness was assessed in terms of days of good
      pain control and days on initial treatment. Costs included those of baseline pain
      management, including breakthrough pain; co-medication costs; and control of
      adverse events. Fentanyl-TTS was more effective than SR-morphine in achieving
      good pain control (99 vs. 64 days, respectively) and the incremental cost
      effectiveness of fentanyl-TTS was US dollars 10.26 per extra day of good pain
      control. Patients treated with fentanyl-TTS remained considerably longer on
      initial treatment compared with those treated with SR-morphine (166 days vs. 117
      days, respectively). The results of this study suggest that fentanyl-TTS is a
      competitive therapeutic and economic choice for the treatment of chronic
      noncancer pain.

PMID- 14649388
TI  - Community hospital physician and nurse attitudes about pain management.
AB  - An interdisciplinary committee was established and charged with examining pain
      management and developing interventions at a 148 bed community hospital. To
      examine strategies on managing pain from both healthcare provider and patient
      perspectives, the committee surveyed the attitudes of physicians and nurses
      toward pain management and patients' opinions about the pain management they
      received in the hospital. A separate survey instrument was developed for
      physicians, nursing staff and patients. Physicians and nursing staff from all
      departments were asked to complete the survey during departmental meetings in
      Autumn 2000, and all patients for whom pain medication were ordered during the
      month of May 2000 were asked to participate. A total of 45 physicians, 142 nurses
      and 169 patients responded. Results showed that the majority of physicians
      (88.9%, n = 40) and nurses (83.0%, n = 118) were satisfied with the pain
      management outcomes in their patients, and that 91.1% of physicians and 90.2% of
      nurses included their patients in the pain management decision-making process.
      Nearly all patients believed their pain was adequately managed, but the results
      indicated a need to improve the use of pain assessment scales by the hospital
      staff and a need to educate and involve all patients in their pain management
      options. Survey data also showed a desire for staff education on pain management.

PMID- 14649387
TI  - Potential cardiovascular effects of COX-2 selective nonsteroidal antiinflammatory
      drugs.
AB  - The newly developed nonsteroidal antiinflammatory drugs (NSAIDs) that selectively
      inhibit cyclooxygenase-2 (COX-2), are effective against pain and inflammation and
      appear to have less gastrointestinal toxicity than conventional NSAIDs. Their COX
      2 selectivity, however, has raised concerns regarding their cardiovascular
      safety, since they do not inhibit COX-1, the isoform of the enzyme that is active
      in thrombosis and vasoconstriction. At this point there is no conclusive evidence
      that COX-2 inhibitors cause ischemic vascular events, because retrospective post
      hoc analyses conflict one another, and no specific randomized trials have yet
      been done. Renal effects, edema and hypertension appear to be similar between
      conventional NSAIDs and COX-2-selective inhibitors. Aspirin is still required for
      patients with cardiovascular risk who are prescribed a COX-2-selective inhibitor.

PMID- 14649389
TI  - Pain management in a long-term care facility: compliance with JCAHO standards.
AB  - An analysis of the treatment of nonmalignant pain in the elderly at a long-term
      facility was conducted to allow development of a pain management program that
      complies with both JCAHO guidelines for pain management and with the Tennessee
      Medicaid (TennCare) reimbursement schedule, and to determine if tramadol can meet
      the standards of pain management under these new guidelines. Inclusion criteria
      were residence in our long-term care facility; a pain intensity score > 4 on a
      modified Wong Baker Pain Scale; the patient having prescription orders for one or
      more of the following drugs: propoxyphene, meperidine, or high dosages of
      acetaminophen (approaching 4 g/day); suspected neuropathic or mixed
      nociceptive/neuropathic pain; and/or a diagnosis of diabetes, osteoarthritis, or
      degenerative joint disease. Exclusion criteria were history of seizures, history
      of opioid or alcohol abuse, and demonstrated hypersensitivity to tramadol or
      opioids. Tramadol administration began at a dose of 25 mg/day titrated up to a
      maximum of 300 mg/day over a 16-day period. Data were collected from computer
      records, dispensing reports, medication administration reports (MARs), current
      federal minimum data set (MDS) data, and weekly care plan meetings. Data were
      tabulated at baseline and 4-6 weeks after a stable dose of tramadol had been
      established. Fourteen residents (mean age 85 years, 1 male, 13 female) met the
      criteria and received tramadol up to 300 mg/day (qid). Tramadol reduced the
      residents' pain scores from an average of 6 to 2 using the Modified Wong Baker
      Pain Scale, reduced the percentage of residents taking propoxyphene from 50% to
      14%, and reduced those taking high doses of APAP or APAP products from 43% to
      14%. Tramadol reduced the percentage of residents falling, losing weight, showing
      no change or decline in activities in daily living (ADLs), displaying
      inappropriate behavioral symptoms, suffering depression, and/or taking
      psychotropic medications. In the state of Tennessee, new reimbursement schedules
      by TennCare have allowed our hospital to comply with the JCAHO standards of
      "optimal achievable care" for the treatment of pain by allowing the hospital
      staff to treat patients with newer, safer, more effective analgesics such as
      tramadol. Early results from this ongoing study have shown that tramadol can
      provide a safe and effective treatment on non-malignant pain in a long-term care
      facility and improve adherence to JCAHO and TennCare standards for proper pain
      management.

PMID- 14649390
TI  - The Kansas Living Initiatives for End-of-Life Care.
AB  - The Kansas Living Initiatives for End-of-Life Care (LIFE) project was formed in
      1999 by over 70 Kansas organizations, agencies and associations to further the
      cause of dignified, comfortable and peaceful end of life in terminally ill
      patients. LIFE developed a module on end-of-life care that was added to the
      Kansas year 2000 Behavioral Risk Factor Surveillance system, convened meetings of
      partners including health professional licensing boards, reviewed state laws and
      regulations, and published a joint policy statement of the Kansas Boards of
      Healing Arts, Nursing and Pharmacy on the use of controlled substances for pain
      management. Activities of Project LIFE and outcomes are described.

PMID- 14649391
TI  - Report from the 10th World Congress on Pain.
AB  - The 10th World Congress on Pain, the triennial meeting of the International
      Association for the Study of Pain, continued the series' tradition as one of the
      premier international meetings for pain clinicians and scientists. At this
      meeting, held in August 2002 in San Diego, California, a broad spectrum of topics
      was presented, with substantial representation in both the clinical and basic
      science realms. Increased understanding of basic pain mechanisms, potential new
      targets for drug treatment of pain, ethical issues, and psychological
      interventions for pain were all areas of considerable interest.

PMID- 14649392
TI  - Treatment of neuropathic orbital pain with gabapentin.
AB  - We report and discuss a case of severe neuropathic orbital pain refractory to
      standard analgesics that responded well to treatment with the anticonvulsant
      gabapentin. Gabapentin may be a useful adjuvant analgesic in the treatment of
      neuropathic pain.

PMID- 14649393
TI  - Pain and palliative care in the Cochrane Library: Issue Number 4 for 2002.
AB  - The Cochrane Library of systematic reviews is published quarterly. Issue 4 for
      2002 contains 2655 reviews of which 1519 are completed and in full text. Nine of
      those are directly relevant to pain management and palliative care. Annotated
      bibliographies for those nine reviews are provided.

PMID- 14649394
TI  - Management of chronic central neuropathic pain following traumatic spinal cord
      injury: executive summary of evidence report/technology assessment: number 45.
AB  - The Executive summary of the federal report on available evidence for management
      of chronic central neuropathic pain following traumatic spinal cord injury is
      presented. This report is one in a series of technology assessment monographs
      commissioned by the Department of Health and Human Services to define current
      state of the art in important health care issues. A comprehensive literature
      search led to conclusions about the diagnosis, assessment and natural history of
      central neuropathic pain. The report documents a dearth of evidence on
      pharmacological therapy and addresses available evidence on central nervous
      system stimulation and lesioning.

PMID- 14649395
TI  - State-by-state report card on care for the dying finds mediocre care nationwide.
AB  - In November 2002, Last Acts issued a state-by-state report on care of dying
      patient sin the United States. The report highlights 'Islands of Excellence'
      despite a grim national picture. The opinion poll conducted by Last Acts shows
      that Americans are dissatisfied and seeking to reduce the financial burden,
      physical pain and emotional stress associated with the end of life.

PMID- 14649396
TI  - The value of twins in dental research.
AB  - Due to recent advances in molecular genetics, studies of twins will continue to
      provide important insights into how genetic and environmental factors contribute
      to variation in human physical and behavioural traits and disorders. This review
      emphasizes that biometrical genetic studies of twins are particularly valuable in
      complementing and directing molecular approaches to facilitate the detection of
      quantitative trait loci. It also describes several other research models
      involving twins, apart from the traditional comparison of similarities in
      monozygotic (identical) and dizygotic (non-identical) pairs, that have the
      potential to provide new information in the future. Current knowledge about the
      genetic bases of common dental problems is summarized and future directions in
      dental research involving twins are outlined.

PMID- 14649397
TI  - Current concepts of the management of dental extractions for patients taking
      warfarin.
AB  - BACKGROUND: Controversy has surrounded the correct management of patients
      therapeutically anticoagulated with warfarin who require dental extractions. The
      risk of bleeding must be weighed up against the risk of thromboembolism when
      deciding whether to interfere with a patient's warfarin regimen. An improved
      understanding of the importance of fibrinolytic mechanisms in the oral cavity has
      resulted in the development of various local measures to enable these patients to
      be treated on an outpatient basis. METHODS: A review of the literature was
      undertaken. This was supplemented by the authors' clinical trials and extensive
      clinical experience with anticoagulated patients. RESULTS: Various protocols for
      treating patients taking warfarin have been reviewed and summarized and an
      overview of the haemostatic and fibrinolytic systems is presented. A protocol for
      management of warfarinized patients requiring dental extractions in the
      outpatient setting is proposed. CONCLUSIONS: Patients therapeutically
      anticoagulated with warfarin can be treated on an ambulatory basis, without
      interruption of their warfarin regimen provided appropriate local measures are
      used.

PMID- 14649398
TI  - Endodontic sequelae of dental erosion.
AB  - BACKGROUND: The incidence of pulp involvement in patients with excessive wear has
      not been extensively documented. METHODS: Clinical records of 448 patients with
      excessive tooth wear were reviewed and 52 cases (11.6 per cent) with near or
      frank pulp exposures or root canal treatments were found and their numbers and
      sites were tabulated. Light microscopy of study models was used to determine
      aetiology at each site of exposure as attrition, erosion or abrasion, scanning
      electron microscopy (SEM) was performed on some individual teeth. RESULTS: Forty
      sites of near exposure and 57 sites of frank exposures or root canal treatments
      were found, some cases had both types of exposure. The commonest sites exposed by
      erosion were the palatal surfaces of maxillary, and the incisal surfaces of
      mandibular anterior teeth. Posterior teeth were not commonly affected. Toothbrush
      abrasion had exacerbated some lesions as shown by SEM. CONCLUSIONS: Endodontic
      sequelae were found in 11 per cent of tooth wear patients as late stages of
      dental erosion. Near and frank exposures of the pulp thus constitute a small but
      significant, problem for the Australian dental profession's concern in the
      management of the tooth wear cases.

PMID- 14649399
TI  - The role of occupational stress in the maladaptive use of alcohol by dentists: a
      study of South Australian general dental practitioners.
AB  - BACKGROUND: It is well recognized that dentistry is a stressful profession.
      However, there are conflicting views about the extent to which such stress
      contributes to hazardous drinking among dentists. In addition, the relative
      contributions of stress and pre-existing vulnerability in predicting alcohol
      problems among dentists generally (and Australian dentists in particular) have
      yet to be determined. METHODS: The levels of stress and alcohol consumption of
      312 South Australian dentists were measured. Factors known to mediate
      vulnerability to alcohol disorders were also assessed with appropriate
      psychometric instruments. RESULTS: High levels of stress/burnout, consistent with
      other studies of dentists' stress, were recorded. Hazardous levels of alcohol
      consumption, which were between two and four times higher than the normative
      South Australian population, were also reported, particularly among males and
      rural dentists. CONCLUSIONS: To a significant extent, stress and hazardous
      alcohol consumption are both present among South Australian dentists. However,
      compared with work stress/burnout, existing personal vulnerability factors are
      much stronger predictors of such hazardous alcohol consumption. We suggest that
      professional dental bodies, and state Dental Boards, may play a role in ensuring
      stress inoculation and guidance on safe limits of alcohol consumption for
      dentists-in-training; and in creating appropriate mechanisms for assisting
      dentists who experience alcohol related difficulties.

PMID- 14649400
TI  - Microtensile bond strengths to caries-affected dentine treated with Carisolv.
AB  - BACKGROUND: Little information is available regarding the bonding performance of
      adhesive restorative materials to caries-affected dentine after the use of
      Carisolv. The aim of this study was to compare the microtensile bond strengths of
      two resin-based adhesives, a conventional glass ionomer cement and resin modified
      glass ionomer cement to 'normal' dentine and caries-affected dentine after
      Carisolv treatment. METHODS: Specimens were prepared using molar teeth with small
      carious lesions. Caries was removed with the Carisolv solution and the whole
      surface was bonded with either SE Bond, One Coat Bond, Fuji IX or Fuji II LC.
      After 24 hours, specimens were prepared for the microtensile bond strength test
      and stressed in tension at 1 mm/min until rupture of the bond. Mean bond
      strengths and mode of failure were determined and analysed with the LSD test and
      chi square test respectively. RESULTS: The results showed no statistical
      difference for SE Bond, One Coat Bond or Fuji IX, but a difference was observed
      for the resin-modified GIC, Fuji II LC. CONCLUSIONS: It was concluded that
      carious dentine treated with Carisolv did not affect the adhesion of the adhesive
      restorative materials tested in this study with the exception of Fuji II LC.

PMID- 14649401
TI  - Minor oral surgical procedures in patients on oral anticoagulants--a controlled
      study.
AB  - BACKGROUND: Patients on therapeutic anticoagulation are at risk of bleeding from
      minor oral surgical sites. When the anticoagulant regime is modified to prevent
      the risk of bleeding, this at the same time predisposes the patient to risks of
      the medical condition for which they are being treated. METHODS: A total of 70
      patients who were on warfarin treatment requiring minor oral surgical procedures
      were treated in the Oral Surgery Department. A control group of 35 had their
      warfarin stopped prior to the minor oral surgical procedure. The other 35 formed
      the study group. Patients with an International Normalized Ratio outside the
      therapeutic range of 2-4, or with history of liver disease or on drugs affecting
      liver function were excluded from the study. Any incidences of post-operative
      bleeding were recorded. RESULTS: None of the patients in either control or study
      group had any serious bleeding complications. CONCLUSION: The data suggest that
      patients can safely undergo routine minor oral surgical procedures without
      alterations of their therapeutic anticoagulation regime.

PMID- 14649402
TI  - Canine eruption into grafted alveolar clefts: a retrospective study.
AB  - BACKGROUND: The contemporary treatment of cleft lip and palate involves a
      sequence of surgical procedures and orthodontic management. Alveolar bone
      grafting (ABG) is usually undertaken after orthodontic expansion of the maxillary
      segments between the ages of eight and 12 years. Two of the important goals of
      alveolar bone grafting are the provision of bony support for the eruption of the
      canine and the closure of residual oro-nasal fistulae. The purpose of this study
      was to retrospectively evaluate the root development and eruption of the canine
      following ABG. METHODS: Group 1: radiographic and clinical records of a sample of
      19 cleft patients who underwent alveolar bone grafting procedures, performed
      between 1996 and 1999 were reviewed. Group 2: a random sample of 15 cleft
      patients attending for routine dental review were clinically examined. The age of
      patient, degree of root development and eruption status of the canine, and
      presence of oronasal fistulae pre and post alveolar bone grafting were evaluated.
      RESULTS: Most cleft canines had continued root development and descended in the
      alveolus towards eruption following ABG. Four canine teeth (8 per cent) were
      impacted and required surgical exposure and orthodontic treatment following
      failure of eruption. Closure of anterior oro-nasal fistulae at the time of
      grafting was maintained post-operatively. CONCLUSIONS: This study demonstrated
      that canine root development and eruption continued satisfactorily through
      grafted alveolar clefts in most cases and closure of anterior oro-nasal fistulae
      was achieved in all cases.

PMID- 14649403
TI  - Dental caries experience in a young adult military population.
AB  - BACKGROUND: The purpose of this study was to investigate a group of young
      Australian adults to determine their caries experience and compare these current
      levels with similar aged cohorts over the past 30 years. Caries experience was
      also related to lifetime exposure of fluoridated water consumption. METHODS: This
      was achieved through a cross-sectional study involving Australian Army recruits
      seen for their initial dental examination at 1st Recruit Training Battalion,
      Kapooka. A total of 499 recruits had a clinical examination with the aid of
      bitewing radiographs and an orthopantogram. Sociodemographic and fluoride history
      data were elicited via a questionnaire. RESULTS: Mean DMFT scores for age cohorts
      were: 17-20 years of age--DMFT 3.59; 21-25 years of age--DMFT 4.63; 26-30 years
      of age--DMFT 7.07; 31-35 years of age--DMFT 9.04. Subjects with a lifetime
      exposure to fluoridated water had significantly lower dental caries experience
      (DMFT 3.80) than subjects with no exposure to fluoridated water (DMFT 5.15).
      CONCLUSIONS: It was found that there has been a decline in the level of caries
      experience in young Australian adults when the data from this study were compared
      to other ad hoc studies.

PMID- 14649404
TI  - An overview of drugs and ancillary equipment for the dentist's emergency kit.
AB  - The concept of a basic (i.e., essential) medical emergency kit suitable for a
      general dental practitioner varies somewhat between different authorities. A
      practitioner's choice is also dependant on the proximity of medical aid and the
      nature of the dental practice. Over recent years the trend has been to restrict
      the items to a minimum, in the interest of both common sense and safety, for
      example, just oxygen, adrenaline 1:1000, an oral carbohydrate source, glyceryl
      trinitrate and aspirin as first options. Ancillary equipment should include an
      oxygen therapy facemask, a pocket mask and a set of oral (Guedel) airways. Two
      further medication options for consideration are an aerosol bronchodilator and,
      in certain circumstances, an injectable antihypoglycaemic agent. This paper
      provides a selective overview of the subject. An absolute necessity is for
      dentists to be competent in Basic Life Support skills, and to maintain a complete
      and current medical history for all patients.

PMID- 14649405
TI  - Crohn's disease with oral presenting signs masquerading as chronic osteomyelitis.
AB  - BACKGROUND: A case of Crohn's disease (CD) was diagnosed following recognition of
      oral and systemic signs and symptoms in a 19-year-old male patient. METHODS:
      Clinical investigation utilized included blood tests (full blood count,
      electrolytes, urea, creatinine, liver function tests), computed tomogrphy scans,
      magnetic resonance imaging scans, oral biopsies, colonoscopy and biopsies of the
      terminal ileum and colon. RESULTS: A diagnosis of CD was made which then allowed
      appropriate medical treatment to be initiated. CONCLUSION: The importance of a
      thorough medical history and full physical examination with appropriate
      investigations as dictated by clinical findings is demonstrated.

PMID- 14649406
TI  - Effects of retinoids on proliferation and plasminogen activator expression in a
      bovine mammary epithelial cell line.
AB  - Effects of two natural (retinol and retinoic acid, RA) and one synthetic N-(4
      hydroxyphenyl) retinamide (4-HPR) retinoids on proliferation and expression of
      urokinase-plasminogen activator (u-PA) by bovine mammary epithelial cells were
      examined. The BME-UV1 established bovine mammary epithelial cell line was used as
      a model system. All retinoids tested (retinol, RA and 4-HPR) were effective
      inhibitors of cell proliferation. When cells were cultured in the absence of
      fetal bovine calf serum (FBCS), inhibition occurred at concentrations as low as 1
      nM for all retinoids tested. The effect of retinoids on cell proliferation was
      not dose-related when cells were cultured in the absence of FBCS. All retinoids
      (retinol, RA, 4-HPR), when used in the range 1 nM-10 microM (noncytotoxic
      concentrations), were equally effective and had identical inhibition patterns.
      Inhibition of cell proliferation by RA was apparent by 6 h and was higher after
      24 h in culture. In contrast, when cells were cultured in the presence of FBCS,
      the effect of RA and retinol on cell proliferation was dose-related. RA and
      retinol inhibited cell proliferation (P<0.01) when added to the culture medium in
      concentrations as low as 10 nM and 100 nM, respectively. 4-HPR was inhibitory
      (P<0.01) in concentrations as low as 1 nM. Higher concentrations of 4-HPR in the
      range 1 nM-1 microM had no further effect on cell proliferation. None of the
      retinoids tested, when added to cultures in the presence or absence of FBCS,
      could completely arrest cell proliferation at noncytotoxic concentrations. RA at
      1 microM inhibited (P<0.05) insulin or IGF-I-induced cell proliferation but had
      no effect (P>0.05) on u-PA mRNA levels or u-PA activity. Furthermore, RA
      inhibited cell proliferation in the presence of FBCS but had no effect (P>0.05)
      on u-PA mRNA levels. Thus, retinoids are effective inhibitors of bovine mammary
      epithelial cell proliferation and this growth inhibition does not seem to
      correlate with any changes in u-PA mRNA or u-PA activity.

PMID- 14649407
TI  - Effects of atropine on plasma amino acid profiles and on the synthesis of
      individual milk proteins in dairy cows fed with pasture.
AB  - Effects of atropine on blood plasma amino acid profile and on the yields and
      concentration of milk components were investigated in 12 Friesian cows in early
      lactation. Cows were housed indoors and fed with cut pasture ad libitum. Each cow
      received four treatments over 12 d during a replicated 4 x 4 Latin square
      experiment. Treatments were: control (saline); low dose (L; 30 microg atropine/kg
      body weight (BW)); medium dose (M; 40 microg atropine/kg BW); and 2 x L dose, 2 h
      apart (2 x L). On each of four treatment days, cows were milked at about 7.00,
      after which treatments were administered by subcutaneous injection. Cows were
      milked again at 2 h, 6 h and 10 h after injection. Milk samples were collected at
      each milking. Immediately after the 2 h milking, blood samples were drawn from
      each cow and the second injection was given for the 2 x L treatment. Atropine
      reduced hourly milk yield, and concentrations and hourly yields of total protein,
      casein, whey protein, alpha-casein, beta-casein, kappa-casein, beta-lactoglobulin
      and alpha-lactalbumin, but by differing amounts. Milk concentrations of bovine
      serum albumin and immunoglobulin G were increased by atropine, and overall yields
      of these proteins were mostly unchanged. Atropine lowered concentrations of most,
      but not all, amino acids in blood plasma, with essential amino acids reduced more
      than non-essential amino acids. Concentrations of alpha-amino N in whole blood,
      and glucose and insulin in blood plasma, fell after atropine injection. There was
      no difference between the L and M doses of atropine, but the 2 x L dose had
      greater effects on milk composition than the single doses. For yields of milk and
      milk components, the effect of the 2 x L dose was also more persistent. The
      results highlight the differential synthesis of individual milk proteins, and
      suggest that atropine might be useful for evaluating the mechanisms regulating
      milk protein composition.

PMID- 14649408
TI  - Haptoglobin and serum amyloid A in milk and serum during acute and chronic
      experimentally induced Staphylococcus aureus mastitis.
AB  - Local and systemic changes in the acute phase proteins, haptoglobin and serum
      amyloid A (SAA), were studied in six dairy cows during the acute and chronic
      phases of experimentally induced Staphylococcus aureus mastitis. Haptoglobin and
      SAA were measured in serum, and in milk from infected and healthy control udder
      quarters within each cow. Concentrations of haptoglobin and SAA increased rapidly
      in both serum and milk during the acute phase of mastitis and followed a similar
      pattern. Significantly raised milk concentrations of SAA were also found during
      chronic subclinical mastitis. Serum concentrations of SAA also tended to be
      higher during the chronic phase than pre-infection. Increases in milk haptoglobin
      and SAA were specific for the infected udder quarters. In conclusion, measurement
      of SAA in milk samples could be a useful tool in diagnosing mastitis.

PMID- 14649409
TI  - Effect of penethamate hydriodide treatment on bacteriological cure, somatic cell
      count and milk production of cows and quarters with chronic subclinical
      Streptococcus uberis or Streptococcus dysgalactiae infection.
AB  - A randomized, controlled field trial was performed in The Netherlands to
      determine the therapeutic efficacy of parenteral penethamate hydriodide
      (Leocillin) against naturally occurring, chronic, streptococcal mastitis during
      lactation. Quarter milk samples were collected from subclinical cases of
      Streptococcus uberis or Streptococcus dysgalactiae mastitis to determine the
      effect of treatment on bacteriological cure and somatic cell count (SCC) at
      quarter level. A quarter was considered to be cured when the bacterial species,
      isolated prior to treatment, was not isolated from the quarter milk samples taken
      on days 10 and 20 post-treatment (bacteriological cure), or when a quarter milk
      SCC (QMSCC) was <250000 cells/ml on days 10 and 20 post-treatment (SCC cure).
      Longitudinal data analysis was performed to determine the effect of antibiotic
      therapy on SCC and milk yield at cow level. Bacteriological cure occurred in 59%
      of 29 treated quarters, while no cure was observed in any of the 21 untreated
      control quarters. Treatment resulted in a significant decrease in SCC at cow and
      quarter level in comparison with untreated controls. There was no significant
      effect of treatment on milk production. Antibacterial treatment of subclinical
      streptococcal infections during lactation also prevented clinical mastitis.
      Furthermore, the treatment may contribute to reduction of bulk milk SCC and to
      prevention of pathogen spread in dairy herds.

PMID- 14649410
TI  - A case of sporadic ovine mastitis caused by Listeria monocytogenes and its effect
      on contamination of raw milk and raw-milk cheeses produced in the on-farm dairy.
AB  - We describe a case of listerial mastitis in a flock of 130 sheep. The animals
      were housed at a farm where the bulk raw ewe milk was processed to produce raw
      milk soft cheese. List. monocytogenes was shed from the right mammary complex.
      Shedding was observed over a period of 99 d. A mean level of 4-56 x 10(4) cfu
      (colony forming units) Listeria monocytogenes/ml was recovered from the raw milk
      originating from the infected udder. The numbers ranged from 9 x10(1) to 2.95 x
      10(5). The bulk milk was contaminated by approx. 5.7 x 10(3) cfu/ml. In the
      cheese product, 2.0 x 10(2) cfu List. monocytogenes/g were constantly detectable
      for a period of 7 d post manufacture. The starter culture used for coagulation
      had a pivotal influence on the behaviour of List. monocytogenes during
      cheesemaking. Using the same mesophilic buttermilk culture as used by the farmer
      allowed numbers of Listeria to increase 60-fold within 12 h owing to a delayed
      acidification of the bulk milk. Addition of a thermophilic yogurt culture reduced
      the numbers of Listeria within 8 h of incubation.

PMID- 14649411
TI  - Tentative hierarchization of the influence of milk properties and technological
      practices on rheological properties of Abondance cheese.
AB  - An attempt at classifying the influence of different characteristics of milk and
      cheesemaking on the rheological properties of Abondance cheese is presented.
      Abondance is a traditional farmhouse French hard cheese with protected
      denomination of origin (PDO). Thirty-nine cheeses made from unpasteurized cows'
      milk were sampled. Spline partial least squares regression was used to relate
      milk properties and cheesemaking practices to rheological properties of the six
      month-old cheeses. These properties were the deformability modulus and the strain
      and stress at fracture measured by compression. Milk properties and technological
      practices had overall the same degree of relationship with the rheological
      properties investigated: plasminogen-derived activity in milk and mineral-protein
      equilibrium, on the one hand, and brining and resting, on the other hand.
      However, acidification kinetics and 1-d pH, which result from both milk
      properties and technological practices, showed the strongest relationships with
      rheological characteristics. Factors that were most appropriate for modelling
      Abondance rheological properties are discussed.

PMID- 14649412
TI  - Effect of specific wavelengths on light-induced quality changes in Havarti
      cheese.
AB  - The effects of exposure of slices of Havarti cheeses to monochromatic light of
      wavelengths 366 nm, 405 nm, and 436 nm, respectively, were studied by tristimulus
      colorimetry, solid-phase microextraction gas chromatographic analysis of
      volatiles, and open-end fluorescence spectroscopy. Having determined the photon
      fluxes of the three wavelengths by ferrioxalate actinometry, it was possible to
      quantify the effects of light exposure in an absolute manner. For all analyses,
      the most severe effects were caused by visible light, leading to colour
      bleaching, change in hue, riboflavin degradation, and formation of the secondary
      oxidation products hexanal, 1-pentanol, and 1-hexanol. Apparent quantum yields
      for formation of hexanal and 1-pentanol were found to be insignificantly
      different for 405 nm and 436 nm exposures, having values of (3-5) x 10(-5) mol x
      einstein(-1) and (9-13) x 10(-5) mol x einstein(-1), respectively. These
      compounds were not formed when exposed to 366 nm light. In contrast, 1-hexanol
      was formed when exposing cheese to all three wavelengths, resulting in apparent
      quantum yields of (2-6) x 10(-5) mol x einstein(-1). The results obtained are
      discussed in relation to the interplay between inherent product colorants, light
      sources, and transmission characteristics of the packaging materials.

PMID- 14649414
TI  - Probiotics induce resistance to enteropathogens in a re-nourished mouse model.
AB  - Nutritional deficiency is commonly associated with impaired immune response and
      the relation between infection and malnutrition is synergic. Probiotics,
      especially lactic acid bacteria are immunomodulatory. The aim was to determine
      whether optimal doses of Lactobacillus casei and yogurt, used as adjuvants in a
      re-nutrition diet in a non-severe malnutrition experimental model, protect
      against Salmonella typhimurium and Escherichia coli. Groups of malnourished mice
      were used, which were re-nourished with milk for 7 or 14 d. After that, both
      groups of mice received the optimal doses of Lb. casei and yogurt supplements. We
      measured IgA+ and IgG+-B cells and phenotypic markers of T lymphocytes; CD3+,
      CD4+ and CD8+ cells. We also determined alphabeta and gammabeta T cell receptor
      (TCR). The ability to protect against Sal. typhimurium and Esch. coli infections
      and specific S-IgA were assessed. Probiotics complemented the effects of the re
      nutrition diet, by stimulating recuperation of the activity of immune cells that
      improved protection against infections.

PMID- 14649413
TI  - Improvement of rheological properties of firm acid gels by skim milk heating is
      conserved after stirring.
AB  - The enhancement of the strength of set acid gels by heating milk was related to
      rheological parameters (water retention capacity, storage modulus) of
      corresponding stirred gels. To obtain accurate rheological data from stirred gel
      it was necessary to maintain a constant granulometry of gel particles and to
      recognize time after stirring as a contributing factor. Two hours after stirring,
      the gel exhibited a higher storage modulus when milk was heated above 80 degrees
      C. A measurement of viscosity of just-stirred yoghurt was sufficient to predict
      correctly the quality of a stirred gel analysed by viscoelastic measurements.
      Increased resistance to syneresis of just-stirred gels was related to higher
      viscosity. The quantity of beta-lactoglobulin (beta-Ig) bound to casein micelles
      explains the improvement of these gel qualities. We have considered that the
      structure of the initial firm gel (mesostructure level) was conserved in
      fragments within the stirred gel. Consequently, the explanation given by various
      authors for the effect of heating milk on the properties of set gels can also be
      applied to stirred gels. The same mechanism, described in literature for
      structure formation of set gels from acidified milk is purposed to explain the
      role of heating milk on the recovery of gel structure after stirring. The beta-Ig
      association with casein micelles during heating favoured micelle connections
      during the acidification. It also favoured the association of gel fragments after
      stirring during the recovery in gel structure.

PMID- 14649415
TI  - Losses of precision associated with simplified designs of milk recording for
      dairy ewes.
AB  - Simplified designs of milk yield recording based on the yield of a single monthly
      milking, adjusted or not for interval between milkings and for production level,
      were simulated and evaluated for 3173 ewe-test-day records belonging to 155
      lactations of Churra dairy ewes. Losses of precision associated with simplified
      methods were evaluated by comparing estimated lactation yields with those
      observed both in a reference plan, where the two daily milkings were recorded at
      weekly intervals, and in the official A4 milk recording (monthly records of the
      two daily milkings). Estimates of lactation yields were less precise when the
      usual monthly designs were compared with a weekly sampling of both a.m. and p.m.
      milkings. The losses of precision were high at 9.4-36.2% including the A4 plan.
      The yield from only the milking period was more predictable than milk yield from
      the whole lactation (suckling and milking periods) and should consequently be
      adopted in dairy ewes. All options with one daily milking every month were more
      accurate when the corresponding plan was based on, or began with, the a.m.
      milking (loss of precision 14.9-15.8%). There was no evidence of improvement in
      sampling accuracy by adjusting for the preceding interval between milkings or
      production level. For practical and economic reasons, the design alternating a.m.
      and p.m. milkings every month, without adjustment, is suggested for ovine milk
      recording.

PMID- 14649416
TI  - Accuracy of Fourier transform infrared spectrometry in determination of casein in
      dairy cows' milk.
AB  - For practical purposes the casein content of milk is often estimated from the
      crude protein content using a general conversion factor. This is done even though
      it is known that several factors can influence the percentage of casein nitrogen
      in the total nitrogen (casein number). The uncontrolled variation in casein
      number affects optimization of cheese production because casein is a limiting
      factor for cheese yield. Fourier transform infrared spectrometry has recently
      been introduced for casein determination. Using this technique we obtained a
      standard error of prediction (SEP) of 0.033% for casein concentrations in the
      range 2.1-4.0%. The true prediction error was estimated as 0.025%. The
      correlation between casein numbers obtained by reference analysis and infrared
      spectrometry could be expressed by an R2 of 0.73 and an SEP of 0.89 for casein
      numbers in the range 70.7-81.0.

PMID- 14649417
TI  - The use of sedimentation field flow fractionation and photon correlation
      spectroscopy in the characterization of casein micelles.
AB  - Sedimentation Field Flow Fractionation (SdFFF) was combined with Photon
      Correlation Spectroscopy (PCS), to characterize changes in the structure of the
      colloidal particles of reconstituted skim milk of diameter >50 nm (aggregates of
      casein and calcium phosphate known as casein micelles) with the changes in
      partitioning (with the addition of salt) of calcium (Ca), inorganic phosphate
      (Pi) and casein between the serum and colloidal phases of the milk. The number
      weighted particle size distributions are determined. These are well represented
      by a log-normal distribution. Methods are presented for estimating the relative
      contributions of scattering and absorbance to the SdFFF detector signal and for
      taking both into account when analysing SdFFF data. The values found for the
      effective density of the casein micelles were in good agreement with the
      literature and ranged from (1.06-1.08 g cm(-3)) according to the composition of
      micelles. The changes in the scattering intensity as determined by PCS correlated
      with the changes in the particle composition. Although the concentrations of
      colloidal calcium phosphate (CCP) (1.1-3.5 g/kg milk) and micellar casein (18.1
      27.2 g/kg milk) varied considerably only small changes in the size distribution
      of particles >50 nm diameter were observed except for milk to which 30 mmol Pi+10
      mmol Ca/kg milk had been added where the particle size distribution shows a
      swelling of the particles consistent with a lower than expected value for the
      particle density. These observations suggest that the micelles have the ability
      to both lose (depleted micelles) and accommodate (enriched micelles) more casein,
      calcium and inorganic phosphate in their interior, thus confirming the model of
      the micelles which postulates an open structure allowing freedom of movement of
      casein and small ions.

PMID- 14649418
TI  - FTIR determination of ligand-induced secondary and tertiary structural changes in
      bovine plasminogen.
AB  - Human plasminogen undergoes a large tertiary structural change in the presence of
      lysine derivatives (e.g. epsilon-amino caproic acid, EACA). This change
      facilitates human plasminogen activation by human plasminogen activators,
      resulting in elevated blood plasmin levels. It is hypothesized that this
      structure-function relationship is similar for bovine plasminogen. The objectives
      of this study were to investigate the effect of the ligand EACA on the secondary
      structure of plasminogen (bovine, human, and rabbit) and the tertiary structure
      of bovine plasminogen using Fourier-transform infrared spectroscopy (FTIR).
      Spectra of plasminogen, EACA, and a mixture of plasminogen and EACA in water and
      deuterium were collected using FTIR. Fourier-self deconvoluted spectra in the
      amide I region (1700-1600 cm(-1)) were used to detect changes in secondary
      structure of plasminogen after EACA addition. Change in bovine plasminogen
      tertiary structure was determined by comparing ratios of amide II (1600-1500 cm(
      1)) to amide I bond intensities over time for samples in deuterium. No
      differences in secondary structure were observed for any plasminogen in the
      presence of EACA; however, addition of EACA significantly changed tertiary
      structure of bovine plasminogen. This tertiary structural change indicates a
      transition from a folded to an unfolded state, which could be more easily
      converted to plasmin. These results are consistent with reported human
      plasminogen studies using neutron scattering (tertiary structure) and circular
      dichroism (secondary structure) methods.

PMID- 14649419
TI  - Biochemical characterization of buffalo (Bubalus bubalis) milk lysozyme.

PMID- 14649420
TI  - Population genetic structure of earthworms (Lumbricus rubellus) in soils
      contaminated by heavy metals.
AB  - The genetic structure of earthworm (Lumbricus rubellus) populations from plots (N
      = 3) contaminated by sewage sludge (containing Cd, Cu, Pb, Zn) and reference
      plots (N = 3) was compared. Earthworms (N = 30-40 per plot) were collected during
      May 2000 and electrophoretic analyses were used to assess genetic variation at
      three polymorphic loci (GPI, LAP, PGM). Allele and genotype frequencies for GPI
      and PGM differed significantly between sludge and reference populations. Sludge
      populations were characterized by a reduced frequency of the most common genotype
      and allele at these loci, and the presence of alleles not found in the reference
      population. Allele and genotype frequencies did not differ significantly among
      individual plots within the sludge or the reference population. These results
      suggest that certain alleles and genotypes may be more sensitive to the effects
      of heavy metals. Multi-locus heterozygosity was significantly higher in the
      sludge population compared to the reference population; the proportion of
      individuals heterozygous at two or more loci was more than 15% higher in the
      sludge population. Results demonstrate that measures of population genetic
      structure in earthworms may represent useful biological indicators for the
      assessment of impacted terrestrial habitats.

PMID- 14649421
TI  - Haem peroxidase activity in Daphnia magna: a biomarker for sub-lethal toxicity
      assessments of kerosene-contaminated groundwater.
AB  - A novel biomarker was developed in Daphnia magna to detect organic pollution in
      groundwater. The haem peroxidase assay, which is an indirect means of measuring
      oxidase activity, was particularly sensitive to kerosene contamination. Exposure
      to sub-lethal concentrations of kerosene-contaminated groundwater resulted in a
      haem peroxidase activity increase by dose with a two-fold activity peak at 25%.
      Reproduction in D. magna remained unimpaired when exposed to concentrations below
      25% for 21 days, and a decline in fecundity was only observed at concentrations
      above the peak in enzyme activity. The measurement of haem peroxidase activity in
      D. magna detected sublethal effects of kerosene in just 24 h, whilst offering
      information on the health status of the organisms. The biomarker may be useful in
      determining concentrations above which detrimental effects would occur from long
      term exposure for fuel hydrocarbons. Moreover, this novel assay detects exposure
      to chemicals in samples that would normally be classified as non-toxic by acute
      toxicity tests.

PMID- 14649422
TI  - Effects of aniline--an aromatic amine to some freshwater organisms.
AB  - We determined the acute and chronic toxicity of aniline to tilapia (Oreochromis
      mossambicus), cladoceran crusatcea (Moina micrura) and oligochaete worm
      (Branchiura sowerbyi) using static bioassay tests. The 96h LC50 values of aniline
      for O. mossambicus, M. micrura and B. sowerbyi were 69.4, 0.6 and 586 mg l(-1)
      respectively. Tilapia responded to even low concentrations of aniline: the fish
      lost appetite at aniline concentrations as low as 0.02 mg l(-1). A 90 d outdoor
      bioassay with tilapia showed that 0.02 mg l(-1) aniline reduced fish yield,
      specific growth rate and food conversion efficiency. Reproductive functions of
      fish were affected by aniline at a concentration of 0.5 mg l(-1) and above.
      Dissolved oxygen, primary productivity and plankton population of the test medium
      also were significantly reduced at 2.65 and 6.94 mg l(-1) aniline.

PMID- 14649423
TI  - The biology of Oreochromis niloticus in a polluted canal.
AB  - In the present investigation, length-weight relationship, condition factor, age,
      growth, mortality, gonadosomatic index (GSI) and fecundity of tilapias (Bolti in
      Arabic): Oreochromis niloticus, from Shanawan drainage canal (SDC), Al-Minufiya
      Province, Egypt, were studied. This was carried out on 162 fish samples collected
      during the period from April 1992 to May 1993. Oreochromis niloticus was found to
      attain sexual maturity early (8-9 cm), was more fecund (1,234-3,893) and has high
      mortality rates (91% for males and 94% for females). A comparison of the various
      parameters of O. niloticus from SDC with those of other authors in different
      localities and times in Egypt revealed year-to-year and geographically
      significant differences in relation to variation in weight with length, condition
      factor, fecundity, growth and mortality rates. These differences were discussed
      and were found to be attributed to the effect of eutrophication and pollution on
      the growth, age and other biological aspects of O. niloticius. Multiple
      regression analysis showed that only female GSI correlated significantly with
      pesticides and heavy metals contamination.

PMID- 14649424
TI  - Antioxidant enzyme activities, metallothioneins and lipid peroxidation as
      biomarkers in Ruditapes decussatus?
AB  - Antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidases (GPX)) were studied in the gills and digestive gland of clams
      Ruditapes decussatus from different sites of the Ria Formosa (south coast of
      Portugal) in order to validate these enzymes as biomarkers of metal exposure. Two
      other potential biomarkers, lipid peroxidation expressed as malondialdehyde
      (MDA), and metallothionein (MT) levels were also measured. This study
      demonstrates that mitochondrial and cytosolic SOD activity changed while CAT
      activity (cytosolic and mitochondrial) was higher in the gills of clams from the
      three sites affected by different sources of contamination. GPXs (total and Se
      dependent) were inhibited in the gills of clams from sites A (directly influenced
      by sewage industrial wastes) and B (directly influenced by harbor facilities). MT
      and MDA levels were higher in the gills of clams from these two sites and in the
      digestive gland of clams from the third site (C, main navigation channel and
      exchange with Atlantic ocean). These results suggest that CAT and GPX activities
      and MDA levels especially in the gills of clams can be used as biomarkers for
      monitoring environmental pollution.

PMID- 14649425
TI  - Toxicity of lithium to three freshwater organisms and the antagonistic effect of
      sodium.
AB  - Lithium (Li) is the lightest metal and occurs primarily in stable minerals and
      salts. Concentrations of Li in surface water are typically <0.04 mg l(-1) but can
      be elevated in contaminated streams. Because of the general lack of information
      concerning the toxicity of Li to common toxicity test organisms, we evaluated the
      toxicity of Li to Pimephales promelas (fathead minnow), Ceriodaphnia dubia, and a
      freshwater snail (Elimia clavaeformis). In the laboratory, the concentration of
      Li that inhibited P. promelas growth or C. dubia reproduction by 25% (IC25) was
      dependant upon the dilution water. In laboratory control water containing little
      sodium (approximately 2.8 mg l(-1)), the IC25s were 0.38 and 0.32 mg Li l(-1) and
      in ambient stream water containing approximately 17 mg Na l(-1), the IC25s were
      1.99 and 3.33, respectively. A Li concentration of 0.15 mg l(-1) inhibited the
      feeding of E. clavaeformis in laboratory tests. Toxicity tests conducted to
      evaluate the effect of sodium on the toxicity of Li were conducted with fathead
      minnows and C. dubia. The presence of sodium greatly affected the toxicity of Li.
      Fathead minnows and Ceriodaphnia, for example, tolerated concentrations of Li as
      great as 6 mg l(-1) when sufficient Na was present. The interaction of Li and Na
      on the reproduction of Ceriodaphnia was investigated in depth and can be
      described using an exponential model. The model predicts that C. dubia
      reproduction would not be affected when animals are exposed to combinations of
      lithium and sodium with a log ratio of mmol Na to mmol Li equal to at least 1.63.
      The results of this study indicate that for most natural waters, the presence of
      sodium is sufficient to prevent Li toxicity. However, in areas of historical
      disposal or heavy processing or use, an evaluation of Li from a water quality
      perspective would be warranted.

PMID- 14649426
TI  - Review of lithium in the aquatic environment: distribution in the United States,
      toxicity and case example of groundwater contamination.
AB  - Lithium is found at low concentrations in the major rivers of the United States
      (about 0.002 mg l(-1)) and as a mineral or salt in pegmatites and brines. The
      United States produces many lithium materials and consumes the greatest amount of
      Li in the world for use in ceramics, glass, aluminum, pharmaceuticals, batteries,
      etc. From 1950 to 1970, Li was central to many nuclear-related US Department of
      Energy (DOE) activities. The historical and current use of Li has not prompted
      many studies of the toxicity of this element to aquatic organisms. Here, we
      review the distribution and use of Li in the US with emphasis on usage by DOE. We
      also summarize information on the toxicity of lithium to aquatic biota. A case
      example is provided which demonstrates the potential for contamination of
      groundwater with Li, evaluates the toxicity of the Li-contaminated groundwater,
      and identifies a treatment alternative.

PMID- 14649428
TI  - Paying for performance: Medicare should lead.

PMID- 14649429
TI  - The outlook for hospital spending.
AB  - Hospital use and spending greatly increased in 2001 and 2002, reversing a long
      term trend. In this paper we contend that the forces driving current hospital
      expenditures are more likely to continue than they are to abate. If current
      trends continue, real hospital spending per capita will increase 75 percent
      between 2002 and 2012, and the demand for hospital beds will increase
      considerably. We discuss numerous forces that will contribute to spending growth,
      including technology, which is likely to continue to raise costs. We also find
      that hospital spending by baby boomers grew more rapidly than that of the
      elderly, a change in trend that could presage increased spending as this cohort
      moves into higher-spending age groups.

PMID- 14649430
TI  - Does the aging of the population really drive the demand for health care?
AB  - In the debate on health policy, it is widely believed that the aging of the U.S.
      population is a major driver of the annual growth in the demand for health care
      and in national health spending. This essay draws on the research literature and
      on data from the Medical Expenditure Panel Surveys (MEPS) to debunk that myth.
      Although in any year per capita health spending for people age sixty-five or
      older tends to average three to five times that for younger Americans, the aging
      of the population is too gradual a process to rank as a major cost driver in
      health care.

PMID- 14649431
TI  - Does U.S. hospital capacity need to be expanded?
AB  - Some industry experts believe that U.S. hospital capacity--especially emergency
      and inpatient services--is being stretched to its limits. Using data from the
      Community Tracking Study, this paper examines constrained hospital services,
      contributing factors, and hospitals' responses. Most hospitals studied had
      emergency capacity problems, but problems in other service areas were limited to
      only a few hospitals. Hospitals have added or converted capacity, improved
      capacity management, dealt with nursing shortages, and worked with public
      officials to reduce emergency department diversions. Although additional capacity
      might be needed in some markets, better management of existing resources could be
      a more effective solution.

PMID- 14649432
TI  - Focused factories? Physician-owned specialty facilities.
AB  - Using data from Round Four of the Community Tracking Study site visits, this
      paper describes the recent rapid increase in physician-owned specialty hospitals
      and ambulatory surgery centers, reasons for this increase, possible impacts, and
      potential policy options. These facilities could lead to excess capacity,
      provision of unnecessary services, and lower quality because of decreased volume
      at some facilities. They also could reduce community hospitals' net revenue and
      thus their ability to subsidize socially necessary but unprofitable services. But
      regulatory intervention should be cautious, because data on impact are
      inconclusive, and these facilities could have the potential to function as
      "focused factories" that improve quality and reduce costs.

PMID- 14649433
TI  - Comparing the mix of patients in various outpatient surgery settings.
AB  - Medicare's facility payment rates for an ambulatory surgical procedure differ
      among settings. These differences raise questions about how Medicare should pay
      for the same procedure in various settings. In exploring this issue, it is
      important to look at whether the type of patients treated varies by setting. The
      recent growth in specialty facilities offers another reason to analyze the mix of
      patients. This study compares the medical complexity of Medicare beneficiaries
      treated in ambulatory surgical centers (ASCs) and outpatient departments.
      Outpatient departments treat beneficiaries who are more medically complex, so
      ASCs might incur lower costs when providing similar procedures.

PMID- 14649434
TI  - Trends in hospital consolidation: the formation of local systems.
AB  - During the past decade the hospital industry has made profound organizational
      changes, including the extensive consolidation of hospitals through merger and
      the formation of hospital systems. Although the rate of hospital system
      acquisitions may be slowing, the local presence of hospital systems is growing.
      Locally concentrated systems have been formed by both for-profit and nonprofit
      hospitals. Researchers have tended to ignore acquisitions or have portrayed
      system formation as primarily an issue of hospital ownership conversion, thereby
      focusing on the expansion of national, for-profit systems. This has left a large
      gap in policymakers' understanding of how locally concentrated systems may affect
      patient care and competition.

PMID- 14649435
TI  - Critical issues in hospital antitrust law.
AB  - Antitrust litigation involving hospitals is common. This paper describes recent
      developments and underlying issues in antitrust law with respect to hospital
      hospital relations, hospital-physician relations, and hospital-payer relations. A
      key unanswered question in each of these areas is how government regulation and
      public purchasing affect competitive markets for hospital services.

PMID- 14649436
TI  - Protecting competition and consumers: a conversation with Timothy J. Muris.
      Interview by William Sage.
AB  - In this interview with William Sage of Columbia University, Federal Trade
      Commission (FTC) chair Timothy Muris discusses his commission's role in the
      health care arena. He details the FTC's antitrust and consumer protection
      activities in a variety of sectors, including hospitals, physicians, and
      pharmaceuticals. Muris affirms the commission's belief that markets benefit
      consumers and that markets need basic rules to operate. The FTC's role is to
      enforce those rules, based on empirical evidence, in as much of the economy as
      possible, including health care.

PMID- 14649437
TI  - Estimating the mission-related costs of teaching hospitals.
AB  - Academic health centers and other teaching hospitals face higher patient care
      costs than nonteaching community hospitals face, because of their missions of
      graduate medical education (GME), biomedical research, and the maintenance of
      standby capacity for medically complex patients. We estimate that total mission
      related costs were dollar 27 billion in 2002 for all teaching hospitals, with GME
      (including indirect and direct GME) and standby capacity accounting for roughly
      60 and 35 percent of these costs, respectively. To assure their continued ability
      to perform important social missions in a competitive environment, it may be
      necessary to reassess the way in which these activities are financed.

PMID- 14649438
TI  - Financing teaching hospital missions: a context.
AB  - The issue of what teaching hospitals do, how much it costs, and how it should be
      financed has been the subject of ongoing debate. This Perspective provides a
      context for considering the implications of the latest contribution to that
      debate: the paper by Lane Koenig and colleagues that presents new estimates of
      teaching hospitals' mission-related costs. I address the system through which
      teaching hospital activities are financed, the difficulty in identifying and
      estimating the costs of teaching hospitals' missions, and the problems involved
      in determining how those missions should be underwritten.

PMID- 14649439
TI  - Accounting for teaching hospitals' higher costs and what to do about them.
AB  - Academic health centers (AHCs) have higher costs per case and also lower margins
      than either other teaching hospitals or community hospitals. The differences in
      margins stem mostly from differences in the intensity with which similar patients
      are treated, as well as hospitals' ability to generate revenue to cover the costs
      of that greater intensity, rather than graduate medical education per se. How
      much patient care capacity should be supported in AHCs and who should be treated
      with the greater intensity they offer are open questions. If there is to be a
      public trust fund to subsidize AHCs, it should be financed from general revenues.

PMID- 14649440
TI  - What will become of the medical mecca? Health care spending in Massachusetts.
AB  - Massachusetts has been called a "medical mecca." It has also been called the
      world's most expensive health care market. This paper concludes that claims of
      excess costs in Massachusetts are overstated. Massachusetts hospitals have lower
      inpatient costs than peer institutions in other states, yet the state's
      concentration of academic hospitals tilts the system toward higher spending. In
      markets like Massachusetts, there is growing pressure to demonstrate tangible
      benefits to justify the additional costs of academic health centers (AHCs).
      Applying new information technologies to proactively manage patients with
      expensive chronic illnesses is a critical area for future collaboration between
      payers and AHCs.

PMID- 14649441
TI  - Who walks through the door? The effect of the uninsured on hospital use.
AB  - Hospitals are concerned about the implications of an increase in the number of
      uninsured people. Using data from the 1999 Medical Expenditure Panel Survey
      (MEPS), we calculate what percentage of hospital inpatient, emergency department,
      and outpatient visits are accounted for by uninsured people and predict how those
      shares would change under three different scenarios. We find that although the
      burden of the uninsured would remain a severe problem for some hospitals, it
      would not likely increase much for most of them. This finding reflects the
      relatively low utilization rates among those most likely to lose coverage:
      nonelderly, nonpregnant, and nondisabled workers and their families.

PMID- 14649442
TI  - Limits to the safety net: teaching hospital faculty report on their patients'
      access to care.
AB  - Many major teaching hospitals might not be able to offer adequate access to
      specialty care for uninsured patients. This study found that medical school
      faculty were more likely to have difficulty obtaining specialty services for
      uninsured than for privately insured patients. These gaps in access were similar
      in magnitude for public and private institutions. Initial treatment of uninsured
      patients at academic health centers (AHCs) does not guarantee access to specialty
      and other referral services, which suggests that there are limits to relying on a
      health care safety net for uninsured patients. AHCs and affiliated group
      practices should examine policies that limit access for uninsured patients.

PMID- 14649443
TI  - The Medicare world from both sides: a conversation with Tom Scully. Interview by
      Uwe E. Reinhardt.
AB  - Tom Scully, administrator of the Centers for Medicare and Medicaid Services
      (CMS), the nation's largest health insurer, discusses the Medicare program with
      Princeton University economist Uwe Reinhardt. Scully's previous appointments in
      both the public and private sectors have given him a diverse set of experiences
      from which to draw in his current position. He praises the agency's staff for
      devising innovations to cope with a changing health care environment, praises the
      program for continuing to meet most seniors' needs, and staunchly defends the
      Bush administration's focus on the private sector as the way forward for
      Medicare.

PMID- 14649444
TI  - Challenges and opportunities for Medicare's original prospective payment system.
AB  - The Medicare program initiated prospective payment for inpatient hospital
      services in 1983. Although the payment system has achieved many of its goals,
      changes in the health care market and the public nature of the program will
      continue to present both challenges and opportunities for improvement. Looking
      forward, policymakers must consider how to balance paying accurately for services
      with using Medicare to achieve broader policy objectives. Paying for new
      technologies, responding to market segmentation and specialization, and
      encouraging quality improvement must also be addressed. To successfully navigate
      these issues, policymakers and program administrators need accurate and timely
      information.

PMID- 14649445
TI  - Obtaining greater value from health care: the roles of the U.S. government.
AB  - The problems of quality and cost in the U.S. health care system are unlikely to
      be solved without strong leadership from the federal government, which can
      mobilize action to set national priorities for quality; develop and promulgate
      standards for care; and stimulate implementation of performance measures and
      standards for providers. All of these functions would best be carried out by a
      new federal agency. Furthermore, the federal government should design payment
      policies based on the performance standards, invest in needed information
      technology, and invest in research related to improving care and in training
      professionals to support nationwide quality improvement.

PMID- 14649446
TI  - Is the current shortage of hospital nurses ending?
AB  - Although hospitals have experienced many shortages of registered nurses (RNs),
      most have not lasted as long as the current shortage, which began in 1998.
      However, hospital RNs' employment and earnings increased sharply in 2002, which
      suggests that the shortage may be easing. Two-thirds of the increase in
      employment came from older RNs, with the remainder supplied by RNs born in other
      countries. The employment response of older and foreign-born RNs indicates how
      the labor market is likely to respond to future shortages, and it emphasizes the
      challenges confronting policymakers as the RN workforce ages and eventually
      shrinks in size.

PMID- 14649447
TI  - The future of the nurse shortage: will wage increases close the gap?
AB  - In recent years the U.S. media have been reporting a shortage of registered
      nurses (RNs). In theory, labor-market shortages are self-correcting; wage
      increases will bring labor markets into equilibrium, and policy intervention is
      not necessary. In this paper we develop a simple forecasting model and ask the
      question: How high must RN wages rise in the future to end the RN shortage? We
      find that inflation-adjusted wages must increase 3.2-3.8 percent per year between
      2002 and 2016, with wages cumulatively rising up to 69 percent, to end the
      shortage. Total RN expenditures would more than double by 2016.

PMID- 14649448
TI  - The McLawsuit: the fast-food industry and legal accountability for obesity.
AB  - Recent litigation brought by a group of overweight children against the
      McDonald's Corporation that seeks compensation for obesity-related health
      problems has provoked an intense public response. Many have derided this lawsuit
      as representing the worst excesses of the tort liability system, while others
      have drawn parallels to tobacco litigation. Fast-food litigation raises the
      question of where accountability for the economic and public health consequences
      of obesity properly rests. In this paper we consider the reasonableness of the
      claims against fast-food companies and discuss several social effects that the
      litigation may have irrespective of its outcome in court.

PMID- 14649449
TI  - Care for the uninsured in general internists' private offices.
AB  - This paper examines the care of uninsured patients in general internists' private
      practices. More than two-thirds of internists provide at least some charity care,
      usually to their existing patients who have become uninsured. They appear to be
      filling a need for people who are moving between coverage, by helping bridge
      coverage intervals. Approximately two-thirds of all internists accommodate
      uninsured patients by reducing the charge or creating a payment plan, with
      internists who are practice owners much more likely to do so. This care to the
      uninsured is important, especially with growing unemployment rates, because the
      safety net would not be able to absorb these patients.

PMID- 14649450
TI  - Hospitals' behavior in a tort crisis: observations from Pennsylvania.
AB  - Pennsylvania, like many states around the country, is in the throes of a "tort
      crisis." The cost of professional liability insurance for physicians and
      hospitals is escalating rapidly, as its availability shrinks. Many hospitals are
      poorly situated to bear these rising costs, especially in an environment of flat
      reimbursement rates and poor investment returns. This paper examines the impact
      of the liability crisis on Pennsylvania hospitals and the strategies being used
      to weather the storm, including alternative risk financing and closer ties
      between hospitals and affiliated physicians. It concludes by connecting these
      trends to larger medical malpractice policy issues.

PMID- 14649451
TI  - The yellow baby. A young, uninsured patient falls through the cracks of our
      medical system.

PMID- 14649452
TI  - At the end of A day. A young doctor considers an end-of-life decision and the
      love that informs it.

PMID- 14649453
TI  - Battery-powered health insurance? Stability in coverage of the uninsured.
AB  - This study assesses the stability of Americans' health insurance status over a
      four-year period. Relatively few Americans were continuously uninsured for the
      four years 1996 to 1999, but a sizable number of the uninsured lacked a stable
      source of coverage. At least as many people were repeatedly uninsured as
      experienced a single gap in otherwise stable coverage. Given these dynamics,
      policymakers should think of "uninsured" as referring not to people, but rather
      to gaps in coverage over time. Reforms that stop short of universal coverage
      should be evaluated in terms of their likely effects on the continuity and
      stability of coverage.

PMID- 14649454
TI  - Spending for specialized mental health treatment in The VA: 1995-2001.
AB  - The mid-1990s saw dramatic changes in mental health care in the Department of
      Veterans Affairs (VA), the largest provider of such care in the United States.
      Spending for specialized inpatient mental health care fell 21 percent from 1995
      to 2001, while spending for specialized outpatient care rose 63 percent. The
      shift from inpatient to outpatient care was accompanied by rapid increases in
      outpatient medication costs. Overall, the VA reduced the average cost (per VA
      user) of specialized mental health care by 22 percent while it increased the
      number of users of these services by 35 percent.

PMID- 14649455
TI  - Mandated psychiatric treatment.

PMID- 14649456
TI  - Round pegs, square holes.

PMID- 14649457
TI  - Mental health and managed care.

PMID- 14649458
TI  - Physicians facing coverage restrictions.

PMID- 14649459
TI  - Pricing drugs.

PMID- 14649460
TI  - NCCLS publishes hematology standards and guidelines.

PMID- 14649461
TI  - Performance characteristics of the Sysmex XT-2000i hematology analyzer.
AB  - The XT-2000i is a new hematology analyzer combining aperture impedance and
      optical technologies. It is capable of generating a 30-parameter hematologic
      assay on peripheral blood at a throughput of 80 samples per hour. We have
      evaluated the performance characteristics of the XT-2000i analyzer and compared
      them with those of the state-of-the-art XE-2100 analyzer and the manual
      differential count. The XT-2000i compared favorably with the XE-2100 analyzer and
      exceeded the manufacturer's specifications in all parameters tested. The XT-2000i
      has a user-friendly graphical user interface, and there was virtually no downtime
      during the period of evaluation. This analyzer can be recommended as a backup to
      the XE-2100 analyzer or as a stand-alone analyzer in a laboratory with moderate
      volume and a broad complexity of samples.

PMID- 14649462
TI  - Human reticulocytes isolated from peripheral blood: maturation time and
      hemoglobin synthesis.
AB  - A pure population of young reticulocytes was isolated from the blood of healthy
      blood donors by an immunomagnetic technique. The young reticulocytes isolated had
      a larger mean corpuscular volume (MCV) but lower mean corpuscular hemoglobin
      (MCH) and mean corpuscular hemoglobin concentration (MCHC) than reticulocytes in
      peripheral blood. The cells were incubated in vitro for 5 days with hemolysis
      less than 5%. Maturation of reticulocytes was studied with 4 different systems:
      new methylene blue-stained smears and flow cytometry after auramine O, oxazine
      750, or thiazole orange staining. The maturation process from reticulocytes to
      erythrocytes had a half-life of 30 hours estimated by visual counting.
      Reticulocytes analyzed with flow cytometers had half-lives of 20, 28, and 29
      hours with Coulter Epics XL, Sysmex R-1000, and Bayer H*3 devices, respectively.
      Total maturation time was 4 to 5 days. During maturation, the reticulocyte MCV
      gradually decreased with a concomitant increase in reticulocyte MCHC. The
      reticulocytes synthesized hemoglobin, and the MCH of the cells increased
      approximately 7% during the incubation period. Taking into account loss of
      hemoglobin-containing vesicles during reticulocyte maturation, we estimated that
      more than 20% of hemoglobin in erythrocytes was synthesized in reticulocytes
      after release from bone marrow.

PMID- 14649463
TI  - Temporal approach to hematological test usage in a major teaching hospital.
AB  - In the era of slowly increasing laboratory budgets, identifying usage patterns
      can be an important first step in decreasing unnecessary laboratory testing. From
      January 1, 1998, through December 27, 2002, we studied inpatient laboratory
      utilization at the University of Alberta Hospital, a large Canadian teaching
      hospital (665 inpatient beds with an almost 100% continuous occupancy rate). The
      daily numbers of complete blood cell count (CBC), CBC with differential (CBCD),
      international normalized ratio, activated partial thromboplastin time, vitamin
      B12, and red cell folate (FOL) tests were correlated with regularly occurring
      hospital events, such as weekends, statutory holidays, and resident changeover
      dates. Testing for hematological monitoring (CBC, CBCD) at our institution has
      been increasing at an average of 2% to 6% per year with a recent (2001 onward)
      rate of increase in hematological diagnostic testing (vitamin B12 and FOL) of
      close to 10%. As expected, laboratory usage was statistically significantly
      higher on weekdays compared with weekends. During the weekdays, ordering
      frequencies on Monday and Friday were shown to be statistically significantly
      higher than on the other days. A nadir occurred on Thursday and on the weekend.
      This finding was postulated to be due to a combination of attending physician
      unfamiliarity and defensive testing. Resident changeovers did not contribute to
      an increase in Monday laboratory testing, as was initially thought, nor did
      holidays. We believe that we can use our findings to decrease laboratory use.
      First, weekend or midweek use might become the appropriate standard for frequency
      of testing. Second, we must alert attending physicians (and residents who are
      soon to be attending physicians) about their subliminal need to increase testing
      during changeovers.

PMID- 14649464
TI  - Use of the Advia 120 hematology analyzer in the differential cytologic analysis
      of biological fluids (cerebrospinal, peritoneal, pleural, pericardial, synovial,
      and others).
AB  - The centralization of our laboratories and the demand for new parameters to
      measure have led to an increase in the number of biological fluid samples, which
      are generally sent for urgent analysis. Due to this they cannot be processed by
      manual methods. Meeting this increased demand for assistance is a challenge for
      the laboratory, and the challenge has been met by the automated hematology area.
      A study of the reliability of the Advia 120 hematology analyzer has been carried
      out through leukocyte and red blood cell counting of 179 biological fluids:
      cerebrospinal, peritoneal or ascitic, pleural, pericardial, synovial, and others.
      The automated leukocyte counts of cerebrospinal fluid samples containing up to
      0.150 x 10(9) leukocytes/L are correlated with counts obtained with the manual
      reference method in a Neubauer counting chamber (r = 0.958; P = .0001). Applying
      Passing-Bablok regression analysis to these results indicates a slope p of 1.155
      (95% confidence interval [CI], 0.915-1.347) and an ordinate intercept b of 0.0076
      (95% CI, 0.012-0.034), showing the results to be perfectly interchangeable. In
      the comparison of the manual analysis of the leukocyte differential using the May
      Grunwald-Giemsa staining method with the analysis using the automated method, the
      percentage of polymorphonuclear granulocytes of the Advia 120 basophil/lobularity
      method is significantly correlated (r = 0.844; P = .0001) with that obtained with
      the manual count. The results of Passing-Bablok regression analysis (p = 0.859
      [95% CI, 0.58-1.190]; b = 8.8 [95% CI, -12.09-24.2]) indicate that these two
      counting methods are also perfectly interchangeable. Automated leukocyte and
      differential counts of peritoneal or ascitic fluids also show good correlations
      with the manual method, and the results are not statistically different.
      Pretreating synovial fluid samples with hyaluronidase enzyme allows their
      processing on the Advia 120; no significant differences were found between manual
      and automated methods with respect to leukocyte counts and differentials.
      Finally, results with pleural fluid samples indicated that leukocyte and
      differential counts obtained with the Advia 120 showed significant differences
      from results obtained with manual methods because of the high incidence of
      mesothelial, lymphoid, and other tumoral cells in this kind of fluid sample. This
      result shows that use of hematology analyzers is questionable for these kinds of
      samples, especially from oncology patients with tumors. A procedure is proposed
      for the processing of these pleural fluids.

PMID- 14649465
TI  - Performance evaluation of a new compact hematology analyzer, the Sysmex pocH
      100i.
AB  - Medical practitioners are searching for ways to improve the quality and outcome
      of care while decreasing cost. One technological advance that may facilitate this
      is point-of-care testing. The pocH-100i hematology analyzer (Sysmex Corporation,
      Kobe, Japan) is a compact device designed specifically for point-of-care testing
      environments. The analyzer provides a full blood count and a 3-part differential
      leukocyte count. A distinct advantage is that neutrophils are reported
      separately, which is useful for monitoring oncology patients. The device was
      evaluated in accordance with International Council for Standardization in
      Haematology (ICSH) guidelines for precision, linearity, carryover, and effects of
      sample aging. The pocH-100i analyzer was compared with the Sysmex KX-21N device.
      The results for all parameters tested were almost identical. When samples
      including blast cells, immature granulocytes, and nucleated red blood cells were
      excluded, the pocH-100i automated differential compared well with a 400-cell
      manual differential. Results for neutrophils (r2 = 0.996), lymphocytes (r2 =
      0.999), and the "mixed" population of cells (r2 = 0.611) indicated the pocH-100i
      analyzer would be highly suitable for low-volume laboratories and near-patient
      services.

PMID- 14649466
TI  - Comparative study on serum iron determination by different methods.
AB  - Iron is an important trace element in humans. Depletion or overload iron status
      can result in a number of aberrant physiological functions. Determination of
      serum iron is one of the valuable test panels for iron status assessment. A
      comparative study was performed on 3 different methods of serum iron
      determination, nonprecipitating ferrozine colorimetric method, precipitating
      ferrozine colorimetric method, and iron liquicolor cleaning factor colorimetric
      agar-based (CAB) method (Human, Taunusstein, Germany). The correlation
      coefficients between nonprecipitating ferrozine colorimetric method and
      precipitating ferrozine colorimetric method, between nonprecipitating ferrozine
      colorimetric method and iron liquicolor cleaning factor CAB method, and between
      precipitating ferrozine colorimetric method and iron liquicolor cleaning factor
      CAB method were found to be 0.998 (P = .067), 0.999 (P = .067), and 0.951 (P =
      .934), respectively. For a setting with limited resources such as Thailand, use
      of the first analytical technique, nonprecipitating ferrozine colorimetric
      method, is recommended because of its low cost and ease of performance.

PMID- 14649467
TI  - Good practice guidelines for laboratory investigation of hemoglobinopathies.
AB  - A review of the Quality Management Program-Laboratory Services (QMP-LS)
      hemoglobin fraction quantitation/hemoglobinopathy investigation surveys revealed
      recurrent errors in diagnosis of carrier genotypes for serious
      hemoglobinopathies. To address these concerns, QMP-LS developed guidelines for
      laboratory investigation of hemoglobinopathy syndromes. The guidelines are based
      on current practice in the province of Ontario, expert opinion in the field, and
      a review of recent literature. They include an overview of the clinical
      significance of the hemoglobinopathies, the indications for a hemoglobinopathy
      investigation, key components of a thorough laboratory hemoglobinopathy
      investigation, interpretation of investigation results, diagnosis of rare
      hemoglobin variants, and indications for DNA investigation of hemoglobinopathies.
      The guidelines present various tables and figures outlining mean cell volume
      reference intervals, recommended hemoglobinopathy investigative techniques,
      recommendations for further investigation of abnormal findings, and algorithms
      for interpretation of the various laboratory hemoglobinopathy investigative
      techniques. The guidelines are intended for use in the processing of specimens
      when a clinical or laboratory physician has ordered a hemoglobinopathy
      investigation (hemoglobin electrophoresis).

PMID- 14649468
TI  - The stability of basic fibroblast growth factor in sera stored at -80 degrees C.

PMID- 14649469
TI  - Platelet parameters in Toxoplasma gondii IgG-seropositive subjects.

PMID- 14649470
TI  - Principles of psychosocial assessment of adolescents.
AB  - Psychosocial and mental health problems are quite prevalent among adolescent
      worldwide, some data reporting up to 20% of adolescents having such problems. A
      number of risk factors, familial, individual and societal, have been indentified
      as contributing to these problems in adolescents. There are also many factors,
      such as family and societal connectedness, that protect adolescents from engaging
      in health risk behaviors that lead to psychosocial and mental health problems. A
      careful psychosocial assessment should be an essential part of adolescent health
      care. This paper provides a brief review of the principles of psychosocial
      assessment of adolescents.

PMID- 14649471
TI  - Comparison of blood gas values in arterial and venous blood.
AB  - OBJECTIVE: To compare pH and PCO2 values of simultaneously obtained arterial,
      arterialized capillary, and venous blood samples and also to compare oxygen
      saturation (ASaO2) measured in arterial blood and oxygen saturation by pulse
      oximetry (PSaO2). METHODS: Prospective study was done in the children admitted in
      the Pediatric Intensive Care Unit of Christian Medical College Hospital Vellore,
      requiring critical care. All the three blood gas samples (arterial, capillary and
      venous) were taken simultaneously and analyzed. Oxygen saturation by pulse
      oximetry was also recorded. RESULTS: 50 children aged 14 days to 12 years were
      included in the study. Arterial and capillary pH values were highly correlated
      (r2=0.9024, p<0.0001). Out of 16 children with arterial acidosis 9(56%) were
      identified by capillary blood gas. Arterial and venous pH values also showed good
      correlation (r2=0.8449, p<0.0001). The PCO2 values of arterial and capillary
      blood gases were found to be highly correlated (r2=0.9534, p<0.0001). The
      capillary blood gas accurately reflected the arterial PCO2 in 41 (82%) patients.
      Arterial and venous blood gas PCO2 values had less correlation (r2=0.5917,
      p=0.011). The arterial oxygen saturation (ASaO2) and oxygen saturation by pulse
      oximetry (PSaO2) were correlated moderately (r2=0.7241, p<0.0001). CONCLUSION:
      Even though arterial blood gas analysis is the gold standard, and when an
      arterial blood gas sample cannot be obtained, a combination of arterialized
      capillary blood gas and pulse oximetry can be effectively used in acutely ill
      children of all ages. Venous samples have a good correlation with arterial
      samples for pH but are not useful for monitoring blood gas status in acutely ill
      children.

PMID- 14649472
TI  - Iodine nutritional status of adolescents.
AB  - OBJECTIVE: To estimate the nutritional status of the adolescent tribes in Purnia
      District of Bihar. METHODS: Iodine nutritional status of the adolescent children
      (10-12 yrs) of tribal communities of Purnia District (Bihar) was studied. Urinary
      iodine levels of the children was estimated. Iodine content of the common salt
      samples consumed by the tribals has been determined. Goiter prevalence among the
      children has been assessed. Iodine deficiency status and goiter-proneness of the
      target population has been discussed in the light of the data. RESULT: Total
      goiter prevalence of 11.67% estimated among the tribals from six well populated
      markets. CONCLUSION: The tribals of Purnia District should be encouraged to
      consume iodised salt.

PMID- 14649473
TI  - Attention deficit hyperactivity disorder.
AB  - OBJECTIVE: To identify ADHD children, to show the prevalence of the disorder in
      the age group of 5-12 years and to study their socio-demographic variables,
      associated medical and co-morbid psychological problems. METHODS: This is a cross
      sectional case study of ADHD children presenting to a child guidance clinic in a
      busy pediatric hospital over a one year period. The diagnosis of ADHD was based
      on DSM IV criteria. RESULTS: Of the 238 children referred, 37 were diagnosed as
      ADHD. 64.9% of the referrals were from pediatricians. The prevalence of ADHD in
      pediatric clinic was 15.5%, the inattention subtype was predominant. The mean age
      of boys and girls with ADHD was 8.49 years and 6.82 years respectively. The male
      to female ratio was 6.4:1. Majority of patients were from middle socio-economic
      status belonging to Hindu families. 27.0% of children had developmental problems.
      Oppositional defiant disorder was the most prevalent while depression was the
      least prevalent co morbid problem. CONCLUSION: ADHD is prevalent in India and the
      bunch of these children are mostly presenting to the pediatrician. They need to
      be aware of the profile of this disorder for early detection and intervention.

PMID- 14649474
TI  - Tracheobronchial foreign bodies.
AB  - OBJECTIVE: [corrected] Foreign body inhalation is an extremely serious problem in
      children and sometimes result in sudden death. The current mortality rate from
      foreign body inhalation is between 0% and 1.8% according to various studies. In
      spite of this, undiagnosed and unsuspected foreign bodies still occur in the
      airway. METHODS: Pediatric patients with documented foreign body inhalation,
      treated in the Department of Pediatrics, Bapuji Hospital, JJM Medical College
      during 1997-2000 are included in the analysis. Children with or without positive
      history of aspiration were examined and the diagnosis was made on the basis of
      history, clinical findings, radilogic evaluation and strong index of suspicion in
      those children where reasonable appropriate treatment failed to resolve the
      respiratory symptoms. Bronchoscopy was performed for a suspected foreign body on
      165 children. RESULT: A review of 165 pediatric cases of suspected foreign body
      aspiration revealed, children between 1 and 3 years were found to be very
      vulnerable for aspiration. Majority of children were boys. Over 70% of the
      patients had positive history of inhalation. Only 60% of the patients presented
      immediately, that is within 24 hours after aspiration. Common symptoms were cough
      and respiratory distress. Physical examination showed abnormal finding in 91% of
      cases. Decreased air entry was the significant clinical sign. Obstructive
      emphysema was found in majority of the cases (49.5%). Rigid bronchoscopy under
      general anaesthesia was the preferred method for removal of aspirated foreign
      body. In 65 (61.9%) cases foreign body was lodged in the right main bronchus and
      majority of these were organic in nature, that is 96 (91.43%). CONCLUSION:
      Tracheobronchial foreign bodies should be strongly suspected in pediatric age
      group who present with a suggestive history, even when physical and radiographic
      evidence is absent. The modalities of diagnosis, management and outcome are
      discussed.

PMID- 14649475
TI  - Bacterial antigen detection test in meningitis.
AB  - OBJECTIVE: To evaluate the role of bacterial antigen detection test in
      cerebrospinal fluid (CSF) for a rapid etiological diagnosis of bacterial
      meningitis. METHODS: The study included 36 cases of bacterial meningitis and 14
      controls. Latex particle agglutination test (LPA test) for detection of bacterial
      antigen was done in the CSF using slidex meningitis kit (Biomeriux, France).
      RESULTS: Using LPA test, an etiological diagnosis could be made in 83% cases of
      bacterial meningitis. In contrast, CSF Gram stain and culture showed 36% and 6%
      positivity, respectively. The sensitivity and specificity of LPA test were 83%
      and 100%, respectively. The common etiological organisms were S. pneumoniae, H.
      influenzae type b and N. meningitidis A. S. pneumoniae was encountered in all age
      groups while H. influenzae type b was found only below one year of age.
      CONCLUSIONS: LPA test is a rapid and superior diagnostic tool as compared to CSF
      Gram stain and culture. The study recommends LPA test as an adjunct laboratory
      test for rapid etiological diagnosis of bacterial meningitis for prompt
      institution of proper antibiotics.

PMID- 14649476
TI  - Empyema thoracis.
AB  - Parapneumonic effusion and empyema thoracis remains a significant source of
      morbidity in children, though the overall incidence of empyema thoracis has
      decreased in the past two decades. These conditions pose a dilemma regarding
      evaluation and treatment for the treating physician. This article discusses the
      practical strategies in the management of empyema thoracis in children.

PMID- 14649477
TI  - Current treatment and future directions in neuroblastoma.
AB  - OBJECTIVE: The International Neuroblastoma Staging System (INSS) and Pathology
      Classification (INPC) were applied to analyze the results of treatment of 644
      patients with neuroblastoma treated in Japan during the years from 1995 to 1999,
      and it was found that the pathology classification (INPC) showed the strongest
      relevance to prognosis compared to other factors such as stage, MYNC
      amplification, DNA ploidy and 1p-deletion. Current results of treatment for
      advanced neuroblastoma are still not satisfactory, so innovative therapeutic
      methods have been sought during the past 10 years. METHODS: Prospects for
      irinotecan and recombinant human endostatin (rhEndostatin) were studied
      expertimentally and clinically. RESULTS: Irinotecan is a water-soluble derivative
      of camptothecin, which is isolated from a Chinese tree, Camptotheca acuminata;
      Its effectiveness against neuroblastoma was confirmed by in vivo preclinical
      studies, and phase I clinical trials in Japan concluded the maximum tolerated
      dose of this agent is 160-180 mg/m2/day for 3 consecutive days, repeated after 25
      days off. Phase II trials with this dose began, and we could obtain some
      encouraging results with the clinical use of irinotecan. rhEndostatin has been
      studied in in vivo experimental models. The action of rhEndostatin was quite
      different from those of other cytotoxic chemotherapeutic agents, and continuous
      administration of this substance showed a more marked anti-effect than its
      intermittent use. CONCLUSION: Irinotecan appears to be promising when it is given
      to the patients neuroblastoma, whereas rhEndostatin needs to have more
      preclinical studies before it is used in patients.

PMID- 14649478
TI  - Nutritional support for children with cancer.
AB  - Children with cancer are at risk of suffering from under nutrition, which can
      affect tolerance of therapy and may influence their overall survival. The goals
      of nutritional support in the cancer patient are to achieve and maintain
      desirable weight and to prevent or correct nutritional deficiencies. So early
      identification of patients at high risk for malnutrition is essential. There are
      different options for nutritional support. Oral feeding, when possible, is the
      first line. Enteral nutrition should be considered for those patients who cannot
      consume adequate macronutrients by mouth. Options are nasogastric tube or
      gastrostomy tube feeding. The advantages of enteral nutrition, when compared with
      parenteral nutrition, include better maintenance of the structural and functional
      integrity of the gastrointestinal tract, a decreased risk of bacterial
      translocation, greater ease and safety of administration, more physiologic and
      efficient use of nutrient substrates, decreased hepato-biliary complications,
      improved outcome and cost-effectiveness. Thus, parenteral nutrition should be
      considered if the gut is not functioning adequately to allow the normal
      absorption and digestion of nutrients or if enteral nutritional support is not
      sufficient to meet nutritional needs. Nutritional assessment and support should
      be integrated into treatment protocols for all children with neoplastic diseases.

PMID- 14649479
TI  - Prognostic factors in childhood acute lymphoblastic leukemia.
AB  - Approximately 80% of children and adolsecents with acute lymphoblastic leukemia
      (ALL) can be cured. To reduce the rate of relapses, but also to limit treatment
      toxicity, risk-adapted treatment has been attempted after identifying the most
      specific prognostic factors. In addition to clinical factors such as age and WBC,
      or factors of the leukemic cell such as the immunphenotype and the cytogenetics,
      the in vivo response to therapy has evolved as the most important predictor for
      relapse. The lack of specificity of most prognostic factors stimulated the search
      for more relevant parameters. Detection of residual disease at defined timepoints
      by cytomorphology can provide specific prognostic information, which allows to
      define new risk groups. Detection of minimal residual disease (MRD) by
      identifying clone-specific T-cell receptor- (TCR) or immunglobuline (Ig) gene
      rearrangements is currently being evaluated to extend this approach of testing
      the individual's sucsceptibility to therapy. The high sensitivity of the method
      when indicating fast clearance of leukemia might eventually spare some patients
      of inadequately toxic therapy. Persistent disease is an indication for treatment
      modification and intensification. If standardized tools are used for treatment
      response evaluation, logistics and quality controls are demanding but essential
      for the reliable conduct of such clinical studies.

PMID- 14649480
TI  - Childhood cancer survivors--living beyond cure.
AB  - Advances in diagnosis and treatment along with improved supportive care have
      contributed to the current survival rates for pediatric malignancies. Recent
      concept of a truly "cured child" in pediatric oncology envisages not only a
      biological cure of the disease but a child on par with peers in growth and
      development physically and in achievements and aspirations, both mentally and
      emotionally. Because of the young age of these survivors and their potential for
      longevity, the delayed consequences of therapy may have a serious impact on their
      lives and family at large than do the acute complications of the cytotoxic
      therapies that they had experienced. Though figures from India are not available,
      it has been estimated that, in USA, the prevalence of childhood cancer survivors
      is expected to increase from 1 in 900 persons among young adults to 1:250 persons
      by 2010. Although this constitutes a remarkable medical achievement, the late
      morbidity in this growing survivor population has become an area for concern. It
      is estimated that 50% of the survivors are likely to develop disabilities that
      alter the quality of life.

PMID- 14649481
TI  - Spontaneous biliary perforation: a rare entity in late infancy and childhood.
AB  - Spontaneous perforation of the biliary tract is rare in infants & children with
      less than 100 cases reported in English Literature till date. We report two cases
      of this rare clinical entity in a 9-month-old boy and other of a 2-year old boy.
      Both patients presented with clinical features of acute peritonitis. Laparotomy
      revealed sterile biliary peritonitis with a normal cholangiogram in the infant
      and biliary perforation in other child. Simple drainage in the former and
      cholecystostomy with external biliary drainage in later resulted in a
      satisfactory outcome.

PMID- 14649482
TI  - Brain abscess--an unusual complication of ventriculo-peritoneal shunt.
AB  - The authors report a case of a 10-year-old boy, who was operated for a
      craniopharyngioma with hydrocephalus. He succumbed to delayed development of
      brain abscess and its consequence, secondary to incompletely treated shunt tract
      infection. This unfortunate complication developed, despite the fact that
      conventional steps (removal of VP shunt and intravenous antibiotics) recommended
      for the treatment of VP shunt infection were adopted. The pathogenesis,
      management and review of literature of this extremely rare clinical entity is
      presented.

PMID- 14649483
TI  - Arthritis in HIV.
AB  - A five and half-year-old boy with arthritis involving large joints is reported.
      The child was found to be seropositive for HIV. Various rheumatological
      manifestations have been described in adults with HIV infection. To the best of
      our knowledge, this is the first report of HIV infection presenting as arthritis
      in pediatric age group in Indian literature.

PMID- 14649484
TI  - Aniridia and Wilm's tumor.
AB  - Aniridia (absence of iris) is a congenital, bilateral, uncommon panocular
      disorder. Whereas the occurrence of aniridia in the general population is
      1:50000, it is present in about 1 in 70 patients with Wilm's tumor. This aniridia
      is sporadic and Wilm's tumor in these cases presents at an unusually early age.
      Aniridia was present in two cases out of 60 cases of Wilm's tumor operated at
      PGIMS, Rohtak. Both cases presented below two years of age. The recognition of a
      child with sporadic aniridia should alert to the increased risk of development of
      Wilm's tumor.

PMID- 14649485
TI  - Intestinal neuronal dysplasia type A.
AB  - Intestinal neuronal dysplasia is a rare cause of bowel obstruction in neonates
      and infants, the diagnosis of which poses a formidable challenge to both
      clinicians and pathologists alike. The importance of this entity lies not only in
      the fact that it mimics Hirschsprung's disease, but also in that untreated cases,
      particularly of type A, may prove fatal. The authors describe one such case of
      intestinal neuronal dysplasia of type A, which was diagnosed at autopsy.

PMID- 14649486
TI  - Tricotillomania as an ictal manifestation of partial seizure in a 4-year-old
      girl.

PMID- 14649487
TI  - Obesity amongst affluent adolescent in India.

PMID- 14649488
TI  - Regenerative versus reparative healing in tendon: a study of biomechanical and
      histological properties in fetal sheep.
AB  - Previous studies have shown fetal tissues heal in a regenerative fashion without
      scar formation. The objective of this study is to compare the healing properties
      of adult and fetal tendons. Time-mated pregnant ewes at 80-85 days of gestation
      were utilized. A partial, midsubstance tenotomy was performed in the lateral
      extensor fetal tendons, and analogous tenotomies were created in the maternal
      limbs. One week after injury, the fetal and adult animals were sacrificed, and
      tendons were histologically and mechanically evaluated. Immunohistochemical
      staining for transforming growth factor beta isoform 1 (TGF-beta1) was performed.
      Histologically, a gap with granulation tissue and inflammatory cells was visible
      in the site of wounding in the adult tendons. In the fetal tendons, no
      abnormalities were noted in the wound, with reconstitution of collagen
      architecture. TGF-beta1 expression was low in fetal but upregulated in the adult
      wounds. No significant differences were found in the biomechanical properties
      between groups. We identified regenerative healing properties in injured fetal
      tendon, while adult tendon tissue healed reparatively with scar formation. Fetal
      tendons demonstrated a limited recovery of mechanical properties after injury
      that was no better than that of the adult tendons at seven days. A better
      understanding of the mechanisms of fetal healing may lead to novel therapeutic
      strategies in the clinical setting.

PMID- 14649489
TI  - Influence of anthropometric and mechanical variations on functional instability
      in the ACL-deficient knee.
AB  - Individual variations in joint anatomy, tissue mechanical properties, and muscle
      strength of the knee are believed to affect the clinical outcome of ACL-deficient
      patients, but the effects have not been studied systematically. The impact of
      individual anthropometric and mechanical variation on functional stability of the
      ACL-deficient knee was investigated in this study using a two-dimensional
      mathematical knee model. The model included the tibiofemoral and the
      patellofemoral articulations, four ligaments, the medial capsule, and four muscle
      units surrounding the knee. Simulations were conducted to determine tibial
      anterior translation as well as tibiofemoral and patellofemoral joint loading at
      a single selected position during early stance phase of gait. Incremental
      hamstring muscle forces were applied to the modeled ACL-deficient knee in order
      to examine the level of the hamstring muscle forces required to prevent abnormal
      tibial anterior translation relative to the femur. Simulations were repeated
      using incremental variations in the selected anthropometric and mechanical
      properties of the ACL-deficient knee. It was found that bony geometry of the knee
      joint, especially the slope of tibial plateau, strongly affected both the tibial
      translations in the ACL-deficient knee and the effectiveness of the hamstring
      muscles to compensate for the ACL deficiency. For instance, simulations indicated
      that, due to ACL deficiency, the tibial anterior displacement increased by 9.1 mm
      for a tibial slope angle of 4 degrees compared to 15.2 mm for a tibial slope
      angle of 12 degrees. Future outcome studies for ACL-deficient knee may be
      required to include individual anthropometric and mechanical parameters of the
      knee as covariants.

PMID- 14649490
TI  - Effects of hydration and fixed charge density on fluid transport in charged
      hydrated soft tissues.
AB  - The effects of tissue hydration and fixed charge density on hydraulic
      permeability and creep behavior of cartilaginous tissues have been investigated
      using the triphasic theory and finite element methods. The empirical model for
      hydraulic permeability of uncharged gels and Mackie and Meares (1955) model for
      ion diffusivity were used in the numerical analysis. The hydraulic permeabilities
      of normal and trypsin-treated porcine annulus fibrosus tissues were measured
      indirectly. Analysis of the experimental data from this study and in literature
      indicates that the water content plays a more important role in regulating tissue
      permeability than fixed charge density for normal tissues. A change in
      glycosaminoglycan content will change both triphasic closed-circuit (or
      intrinsic) and biphasic open-circuit permeabilities of cartilaginous tissues.
      Analysis also shows that both fixed charge density and water content play an
      important role in tissue creep response. This study adds new knowledge to the
      permeability and creep behavior of cartilaginous tissues and is important for
      understanding the nutrition in intervertebral disk.

PMID- 14649491
TI  - Effects of a saddle shaped annulus on mitral valve function and chordal force
      distribution: an in vitro study.
AB  - Studies have concluded that the shape of the human mitral valve annulus is a
      three-dimensional saddle. The objective of this study was to investigate the
      effects of a saddle shaped annulus on chordal force distribution and mitral valve
      function. Eleven human mitral valves were studied in a physiological left heart
      simulator with a variable shaped annulus (flat versus saddle). Cardiac output and
      transmitral pressure were analyzed to determine mitral regurgitation volume. In
      six experiments, force transducers were placed on six chordae tendineae to
      measure chordal force distribution. Valves were tested in normal and
      pathophysiologic papillary muscle positions. When comparing the flat and saddle
      shaped configurations, there was no significant difference in mitral
      regurgitation volume 11.2% +/- 24.7% (p = 0.17). In the saddle shaped
      configuration, the tension on the anterior strut chord was reduced 18.5% +/-
      16.1% (p < 0.02), the tension on the posterior intermediate chord increased 22.3%
      +/- 17.1% (p < 0.03), and the tension of the commissural chord increased 59.0% +/
      32.2% (p < 0.01). Annular shape also altered the tensions on the remaining
      chords. Annular shape alone does not significantly affect mitral regurgitation
      caused by papillary muscle displacement. A saddle shaped annulus redistributes
      the forces on the chords by altering coaptation geometry, leading to an optimally
      balanced anatomic/physiologic configuration.

PMID- 14649492
TI  - Effect of stenosis asymmetry on blood flow and artery compression: a three
      dimensional fluid-structure interaction model.
AB  - A nonlinear three-dimensional thick-wall model with fluid-structure interactions
      is introduced to simulate blood flow in carotid arteries with an asymmetric
      stenosis to quantify the effects of stenosis severity, eccentricity, and pressure
      conditions on blood flow and artery compression (compressive stress in the wall).
      Mechanical properties of the tube wall are measured using a thick-wall stenosis
      model made of polyvinyl alcohal hydrogel whose mechanical properties are close to
      that of carotid arteries. A hyperelastic Mooney-Rivlin model is used to implement
      the experimentally measured nonlinear elastic properties of the tube wall. A
      36.5% pre-axial stretch is applied to make the simulation physiological. The
      Navier-Stokes equations in curvilinear form are used for the fluid model. Our
      results indicate that severe stenosis causes critical flow conditions, high
      tensile stress, and considerable compressive stress in the stenosis plaque which
      may be related to artery compression and plaque cap rupture. Stenosis asymmetry
      leads to higher artery compression, higher shear stress and a larger flow
      separation region. Computational results are verified by available experimental
      data.

PMID- 14649493
TI  - Numerical simulation of the flow-induced deformation of red blood cells.
AB  - A theoretical model is presented for describing the flow-induced deformation of
      red blood cells. The cells are modeled as deformable liquid capsules enclosed by
      a membrane that is nearly incompressible and exhibits elastic response to
      shearing and bending deformation. In the mathematical formulation, the
      hydrodynamics is coupled with the membrane mechanics by means of surface
      equilibrium equations expressed in global Cartesian coordinates. Numerical
      simulations are carried out to investigate the deformation of a cell in simple
      shear flow, in the physiological range of physical properties and flow
      conditions. The results show that the cell performs flipping motion accompanied
      by periodic deformation in which the cross section of the membrane in the plane
      that is perpendicular to the vorticity of the shear flow alternates between the
      nearly biconcave resting shape and a reverse S shape. The period of the overall
      rotation is in good agreement with the experimental observations of Goldsmith and
      Marlow for red blood cells suspended in plasma. Parametric investigations reveal
      that, in the range of shear rates considered, membrane compressibility has a
      secondary influence on the cell deformation and on the effective viscosity of a
      dilute suspension. The numerical results illustrate in quantitative terms the
      distribution of the membrane tensions developing due to the flow-induced
      deformation, and show that the membrane is subjected to stretching and
      compression in the course of the rotation.

PMID- 14649494
TI  - Cardiac near-field morphology during conduction around a microscopic obstacle--a
      computer simulation study.
AB  - In a recent paper, we described the behavior of the cardiac electric near-field,
      E, parallel to the tissue surface during continuous conduction. We found that the
      tip of E describes a vector-loop during depolarization with the peak field, E,
      pointing opposite to the direction of propagation, phiI(m). Experimentally
      recorded loop morphologies of E, however, frequently showed significant
      deviations from the theoretically predicted behavior. We hypothesized that this
      variety of morphologies might be caused by conduction obstacles at a microscopic
      size scale. This study examines the influence of obstacles on the morphology of
      vector loops of E and whether the peak of distorted loops remains a reliable
      indicator for the direction of propagation. We used a computer model of a sheet
      of cardiac tissue with a central conduction obstacle immersed in an unbounded
      volume conductor. We studied the loop morphologies of E and the differences
      between the intracellularly determined direction of propagation, phiI(m), and the
      direction of E, phiE. Distortions of the vector loop were morphologically similar
      to those observed experimentally. Differences between phiI(m) and phiE were less
      than 18 degrees at all observation sites. The obstacle led to deformations of the
      loop morphology, particularly during the initial and terminal phases, and to a
      lesser degree near the instant of E. We concluded that E is a reliable indicator
      of phiI(m).

PMID- 14649495
TI  - Ion channel basis for alternans and memory in cardiac myocytes.
AB  - Beat-to-beat alternation in action potential morphology (alternans) in individual
      cardiac cells may be important in the development of ventricular tachycardia and
      fibrillation. So far, it has been difficult to identify the cause for alternans
      at the ion channel level because computer models and experiments that display
      alternans also simultaneously exhibit other confounding rhythm patterns,
      including those attributable to short timescale memory effects. To address this
      difficulty, we have developed an eigenmode method to study the dynamics of
      detailed cardiac cell models under constant pacing. The method completely
      separates these effects from one another in the linear regime, allowing each to
      be studied individually. For the Beeler-Reuter ion channel model, the fundamental
      difference between the alternans and memory modes was found to be rooted in the
      difference in the relative phasings of the x1 and f gate perturbations associated
      with the slow outward and slow inward currents, respectively. The importance of
      this relative phasing was analyzed with the help of two new analytical methods.
      For the alternans case, the relative phasing produced constructive interference
      between the two currents large enough to reverse the perturbation in membrane
      potential from beat to beat. The opposite was true of the memory mode.

PMID- 14649496
TI  - Wall shear stress modulation of ATP/ADP concentration at the endothelium.
AB  - A mathematical model of ATP/ADP reaction at the surface of the endothelium for
      any two-dimensional or axisymmetric nonsingular functional form of the wall shear
      stress has been presented. Excellent agreement is obtained with the numerical
      solution for the parallel plate case. For spatially varying wall shear stress,
      such as the stagnation point flow and a backward facing step the ATP
      concentrations are shown to have a maximum at the stagnation point streamline and
      the reattachment point respectively. Increasing the Reynolds number increases
      both the ATP and ADP concentrations. For the backward facing step significant
      spatial variations occur in the concentration. Hence, a strong controlling factor
      for physiological kinetic values is the geometry of the arterial vessel since
      this determines the wall shear stress and thence the transport to the reactive
      surface. The area of high concentration also occurs where the wall shear stress
      is low (limiting case is zero shear stress). Atherosclerotic plaques are known to
      occur in areas of low wall shear stress and at vessel bifurcations where the wall
      shear stress is spatially varying. The ATP/ADP concentrations at these particular
      points may very well contribute to the formation of plaques.

PMID- 14649497
TI  - Modeling modulation of intracranial pressure by variation of cerebral venous
      resistance induced by ventilation.
AB  - To test, theoretically, the hypothesis that: (1) cyclic extravascular
      compressional modulation of the terminal venous bed occurs with positive pressure
      inhalation; and (2) the degree of modulation is diminished with increasing
      vascular dilation induced by increasing the level of the partial pressure of
      arterial blood carbon dioxide (PCO2), two modifications of Ursino's model of
      cerebrospinal fluid dynamics were made: (1) terminal venous bed resistance was
      synchronously modulated with the ventilation cycle; and (2) both the depth of
      modulation and cerebrovascular resistance were progressively reduced with
      increasing levels of PCO2. Recordings of intracranial pressure (ICP) and arterial
      blood pressure of piglets were obtained and correlated at different levels of
      hypercapnia. Simulated and experimental correlation values progressively
      increased monotonically as the level of PCO2 increased. Group (n = 4) mean values
      of correlation (+/- standard deviation) were 0.54 (+/- 0.17), 0.61 (+/- 0.08),
      0.79 (+/- 0.06), 0.86 (+/- 0.04), 0.87 (+/- 0.05) for respective mean PCO2 levels
      (+/- standard deviation) of 32.9 (+/- 1.75), 41.4 (+/- 2.5), 55.9 (+/- 4.0), 72.5
      (+/- 6.45), and 87.4 (+/- 7.25) mmHg. These results support the stated premise
      that dilation of the cerebrovasculature reduces the influence of positive
      pressure ventilation on the ICP recording by increasing the venous pressure and
      thus diminishing the likelihood of vascular compression.

PMID- 14649498
TI  - Simultaneous measurement of interstitial fluid pressure and load in rat skin
      after strain application in vitro.
AB  - Skin provides the flexible, protective covering of the body. It consists of a
      network of fibrous proteins embedded in a viscoelastic gel. Theoretical models of
      soft tissue demonstrate that behavior of such systems is strongly influenced by
      the relationship between the interstitial fluid pressure (P(if)) and solid matrix
      stress. A microtensiometer for loading skin uniaxially in vitro was, therefore,
      developed and used in conjunction with the established servo-null micropipette
      technique to measure P(if). Dorsal rat skin specimens were preloaded to 100 mN,
      where P(if) was 2.3 +/- 1.3 mmHg (mean +/- SE, n = 12) above ambient, and then
      strained by 4%. Load instantaneously increased and the subsequent decay was
      described by the function, F(t) = F(1)[1-C(f)Ln(t)]. F(1), related to the
      instantaneous elasticity, was 272 +/- 42 mN (n = 12) while, C(f) was 0.0894 +/-
      0.0026 [Ln(s)](-1) (n = 12). A similar function P(t) = P(s)(1) x [1-C(ps)Ln(t)],
      where P(s)(1) = 27 +/- 5 mmHg and C(ps) = 0.1274 +/- 0.0097 [Ln(s)](-1) (n = 12)
      fitted the decay of P(if) after 20 s with a residual > or = 0.82, though, P(if)
      fell more rapidly over the initial 10 s. P(if) and stress can be measured
      simultaneously with the apparatus, though more precise determination of the depth
      at which pressure is measured is required for quantitative comparison of the
      magnitude of these two parameters.

PMID- 14649499
TI  - Biofluid aspects of embryo transfer.
AB  - Embryo transfer (ET) is the last stage of extracorporal fertilization during
      which the embryo is placed in the uterine cavity with a medium-filled catheter 2
      3 days after in vitro fertilization. While fertilization in the laboratory occurs
      at very high rates (> 90%), the overall success of the procedure (i.e., take home
      baby) is still very low (< 25%) and assumed to be mainly due to implantation
      failure. A computational model was developed to simulate ET within the uterine
      cavity by a fluid-filled catheter inserted into a two-dimensional channel with
      oscillating walls. The results showed that the speed at which the embryos are
      injected from the catheter dominates the procedure and controls the velocity of
      their transport within the uterine cavity. ET at excessively high injection
      speeds may lead to ectopic pregnancies, while uterine peristalsis affects
      transverse dispersion only during injection at low injection speeds. The presence
      of the catheter within the uterus does not affect flow patterns downstream of its
      tip. The potential risks to implantation failure due to mechanical factors
      involved in the ET processes are discussed.

PMID- 14649500
TI  - Partitioning of cortical and deep cytoskeleton responses from transient magnetic
      bead twisting.
AB  - We attempted to estimate in living adherent epithelial alveolar cells, the degree
      of structural and mechanical heterogeneity by considering two individualized
      cytoskeleton components, i.e., a submembranous "cortical" cytoskeleton and a
      "deep" cytoskeleton (CSK). F-actin structure characterizing each CSK component
      was visualized from spatial reconstructions at low and high density,
      respectively, especially in a 10-microm-cubic neighborhood including the bead.
      Specific mechanical properties (Young elastic and viscous modulus E and n) were
      revealed after partitioning the magnetic twisting cytometry response using a
      double viscoelastic "solid" model with asymmetric plastic relaxation. Results
      show that the cortical CSK response is a faster (tau1 < or = 0.7 s), softer (E1:
      63-109 Pa), moderately viscous (n1: 7- 18 Pas), slightly tensed, and easily
      damaged structure compared to the deep CSK structure which appears slower (tau2
      approximately 1/2 min), stiffer (E2: 95-204 Pa), highly viscous (n2: 760-1967 Pa
      s), more tensed, and fully elastic, while exhibiting a larger stress hardening
      behavior. Adding drug depolymerizing actin filaments decreased predominantly the
      deep CSK stiffness. By contrast, an agent altering cell-matrix interactions
      affected essentially the cortical CSK stiffness. We concluded that partitioning
      the CSK within cortical and deep structures is largely consistent with their
      respective functional activities.

PMID- 14649501
TI  - Contact deformation of liposome in the presence of osmosis.
AB  - The role of osmotic pressure on the geometry of adherent liposome remains an
      intricate question in the mechanics of supramolecular structures. In this study,
      confocal reflection interference contrast microscopy in combination with cross
      polarized microscopy was applied to probe the geometry of deformed liposome on
      fused silica substrates through the determination of a vesicle-substrate
      separation profile. In parallel, a theoretical model which describes the large
      deformation of the lipid bilayer membrane under both out-plane bending and in
      plane shear forces is developed. Then, the global deformation geometry of the
      adherent liposome is rigorously compared with our experimental data. It is shown
      that the adhesion contact area increases in dimension, the liposome volume
      decreases, and the vesicle height decreases under the reduced osmotic pressure.
      The coupling of experimental data and a modified theoretical framework of the
      adherent liposome provides a more explicit result in comparison with previous
      studies and demonstrates the possibility of modeling the change of liposome
      mechanics under the influence of osmosis.

PMID- 14649503
TI  - SARS and the effect on nurse education in Singapore.

PMID- 14649502
TI  - Incremental mechanics of collagen gels: new experiments and a new viscoelastic
      model.
AB  - Paired incremental uniaxial step (i.e., relaxation) and ramp tests were conducted
      simultaneously on four (nominally) identical samples of type I collagen gel, over
      a direct strain range 0 < epsilon < 0.2. The paired step and ramp responses could
      not both be predicted by a simple viscoelastic constitutive relation (either
      linear or Fung-type), but could be predicted reasonably accurately by a general
      nonlinear viscoelastic relation with a strain-dependent relaxation spectrum, of
      the form sigma(t) = f(t)-infinity g(t-tau,epsilon)[d(epsilon)(tau)/d(tau)]d(tau).
      Based on a four-term exponential-series approximation, we measured the stiffness
      moduli and time constants of the relaxation function, g(t,epsilon), for the four
      gel samples that we tested, and found that the time constants were independent of
      strain but the moduli increased strongly with strain. Further, we found that the
      time constants did not vary across the four gels, but the moduli varied by a
      factor of about 2 across the gels. Some additional tests show features of the
      response of collagen gels to cycles of application and removal of loading.

PMID- 14649504
TI  - A moral imperative to improve the quality of work-life for nurses: building
      inclusive social capital capacity.
AB  - The complexity and incessant change in the corporatised health care workplace has
      influenced nurses' work choices, morale, quality of work-life and the wellbeing
      of patients. Thus, there is an urgent moral imperative to improve the quality of
      work-life for nurses. To this end, it is crucial to re-define progress beyond the
      sole economic markers of success and profit in the health care workplace. This
      paper argues for the identification of ethical markers and indicators of
      organisational success based on bridging and linking social capital which could
      be used to re-organise health care organisations, hence crafting inclusive moral
      spaces where nurses can safely work and provide quality care for patients. Social
      and ethical evaluation is well suited to examine current workplace dilemmas from
      a psychosocial perspective and provide a framework for best practice in building
      capacity in effective social relations and family friendly, ethical workplaces.

PMID- 14649505
TI  - Perceived status of nurses compared to other health care professionals.
AB  - The global shortage of nurses indicates that strategies must be in place to
      attract individuals to the profession. The purpose of this study was to explore
      the specific motivations/influences that encourage students to undertake a
      nursing career, their perceived status of nurses, their perceived goals as nurses
      and their future career pathways. The study involved a cross sectional approach
      using Ford's (1986) taxonomy of human goals as a theoretical framework. A
      questionnaire was administered to 126 nursing students enrolled in the first
      semester of a nursing degree and 80 students in the final semester. Results
      revealed the image of nurses continues to be influenced by the media. Findings
      also show how the perceived status of nurses, within a hospital and community
      setting differ compared to other health care workers. This result highlights the
      participants' lack of knowledge in regard to the role of professionals within the
      health care industry. Results have implications for nurse education (long and
      short term) in relation to the role of nurses.

PMID- 14649506
TI  - 'The ones that got away': implementing an exit policy for nurses in a public
      hospital.
AB  - The shortage of registered nurses in Victoria led a Melbourne metropolitan
      hospital to analyse their recent staff attrition rate. This analysis highlighted
      the importance of having an exiting policy in place for all departing staff. An
      exit policy can provide unique opportunities for hospitals to collect information
      that may help reduce future employee turnover through the identification of the
      causes of employee dissatisfaction. This paper will discuss the literature and
      outline the project that aided in the analysis of the hospital's attrition rate
      and development of a practical exit policy.

PMID- 14649507
TI  - Barriers to conducting randomised controlled trials: lessons learnt from the
      Horsechestnut & Venous Leg Ulcer Trial (HAVLUT).
AB  - The RCT is considered the gold standard for testing a therapeutic intervention.
      However, the conduct of an RCT is not without numerous obstacles. As illustrated
      through the recent Horsechestnut and Venous Leg Ulcer Trial (HAVLUT), these
      barriers can be attributed to randomisation, recruitment, retention, blinding and
      sampling procedures, and to gate keeping. These obstacles, together with
      strategies to prevent and overcome them, are detailed throughout this article,
      and are aimed at ameliorating the future design and conduct of RCTs.

PMID- 14649508
TI  - Poor agreement in application of the Australasian Triage Scale to paediatric
      emergency department presentations.
AB  - BACKGROUND: The Australasian Triage Scale (ATS) is used in Australian emergency
      departments (ED) to describe patient priority on arrival. This study aimed to
      determine the level of inter-rater consistency with which the scale is applied to
      paediatric presentations. Additionally, it sought to document the level of
      certainty with which nurses apply the scale. METHOD: An anonymous survey of
      emergency nurses responsible for paediatric triage decisions using written
      patient profiles. RESULTS: The level of agreement between nurses applying the ATS
      to paediatric presentations can be described as poor and appears lower than the
      consistency with which it is applied to adult presentations. CONCLUSION:
      Inconsistent allocation of ATS category implies variable patient waiting times,
      which may have detrimental effects on patient condition. Hence, efforts must be
      made to address the inconsistency that exists in paediatric triage decision
      making.

PMID- 14649509
TI  - Grappling with the literature in a grounded theory study.
AB  - Student researchers often struggle to understand how to use literature in a
      grounded theory study where timing and knowing what to read are critical. Despite
      substantive theoretical documentation on this topic the reality of working
      through abstract ideas is more challenging. There is a fine line between not
      doing a literature review in the area of study and being informed so that a study
      is focused. In this paper a practical example will be presented illustrating how
      the student can integrate literature yet stay away from preconceived notions. The
      topic is interprofessional practice.

PMID- 14649510
TI  - Liberating clinical effectiveness: a model for consideration.
AB  - This paper explores Habermas' knowledge constitutive interests as a basis for
      clinical effectiveness. Clinical effectiveness and evidence based practice are
      clarified and Habermas interpretation of critical theory is introduced as an
      instrument which could arguably fulfil the needs of both concepts. The knowledge
      constitutive interests have the capacity to encompass science and evidence based
      practice via technical knowledge, the practical interests via interpretive
      knowledge and the freedom to change practice via emancipatory knowledge. This
      gives an opportunity for technical science and interpretive knowledge to
      facilitate the liberation of nurses via clinical effectiveness. The paper
      culminates in the presentation of a visual model to articulate this proposal.

PMID- 14649511
TI  - Falls and injury reduction in residential aged care: translating research into
      practice.
AB  - Falls and falls-related injuries are a major problem in residential aged care.
      While there are many factors contributing to falls in this group, there are also
      a number of strategies that can help reduce falls and associated injuries. While
      programs to prevent falls must be multifactorial and multidisciplinary, nurses in
      residential aged care will play a central role in setting up and coordinating
      such programs. This paper reviews a broad range of nursing, medical and allied
      health literature. It then synthesises the research findings to outline a
      comprehensive series of recommendations that nurses can use to improve clinical
      practice in this area.

PMID- 14649513
TI  - Nurses on the frontline: Canada should recognise its fallen heroes of SARS.

PMID- 14649512
TI  - More than just a virus: the sexual health needs of consumers with HIV and mental
      illness in the third decade of AIDS.
AB  - This paper provides a review of the literature concerning risk taking behaviors
      for HIV amongst the mentally ill and knowledge of HIV/AIDS amongst this group.
      The paper presents a comparison of Australian and international statistics of
      prevalence and new infection rates and outlines the subsequent psychiatric
      complications arising from AIDS. Suggestions are made as to the development of
      appropriate patient sexual health teaching by nurses. Above all the purpose of
      the paper is to inform clinicians and develop discourse concerning the
      implications for clinical practice.

PMID- 14649514
TI  - The NurseLink model of care.

PMID- 14649515
TI  - Unveiling appendicitis.
AB  - The most common reason for performing abdominal surgery is appendicitis, which
      affects up to 12% of the population (Lemone & Burke, 2000). Appendicitis is acute
      inflammation of the vermiform appendix that is typically manifested by localised
      pain in the right lower quadrant of the abdomen (Holmes, 2001; Lemone & Burke,
      2000; McCance & Huether, 2002; Wagner, McKinney & Carpenter, 1996). Abdominal
      pain is a very common complaint. However, pain in the lower right quadrant cannot
      be used as the gold standard in a nursing assessment as an indication of
      appendicitis. Approximately one third of patients with appendicitis will have
      pain that is spread across the abdomen similar to gastritis (Mattice, 1999).
      Therefore a more in depth nursing assessment is required. This paper looks at
      accurately assessing the other signs and symptoms of appendicitis. These may
      include changes in vital signs, behaviour and body positioning and a history of
      anorexia, nausea and vomiting. Unveiling appendicitis requires the performance of
      an accurate and thorough abdominal pain assessment. This competent assessment
      will assist in preventing complications such as perforation and peritonitis and
      ensure a better patient outcome (Wagner, et al., 1996; Wright, 1997).

PMID- 14649516
TI  - The challenge of providing family-centred care during air transport: an example
      of reflection on action in nursing practice.
AB  - This article explores reflection with regard to the nursing practice of a
      transport nurse in caring for ill newborn patients and their family. It examines
      the issue of reflective nursing practice, institutional obstacles, and angst in
      promoting the model of family-centred care, as it applies to newborn infants
      being transported for tertiary care to a hospital some distance away from the
      family's home community. Reflective practice is explored as an epistemological
      link between practice and research, locating one nurse's clinical experience in
      reflection and subsequent action, through clarification of thought-provoking
      issues and generation of research questions.

PMID- 14649517
TI  - Concept mapping the change of a surgical wound dressing.
AB  - Changing a surgical wound dressing is a traditional nursing task that
      incorporates many areas of nursing knowledge. This article describes the
      construction of a concept map to sort the subjective, objective and constructed
      knowledge required to perform this task with optimal wound healing the goal.
      Critical thinking is used to select and exclude information. The use of concept
      maps as a tool to synthesise knowledge is discussed as is how the chosen concept
      incorporates the art and science of nursing care. The concept map displays the
      wholistic assessment of the client and use of nursing knowledge to determine and
      promote wound healing.

PMID- 14649518
TI  - Self-harm in the emergency setting: understanding and responding.
AB  - Nurses are the people most consistently and intensely involved in the care of
      people who present to emergency departments because of self-harm, yet most have
      received no training or support to provide strategic care. This paper will
      explore unique features of the emergency context for care and provide practical
      instruction on how nurses working in the area can respond effectively. As this
      paper argues there is much that the emergency nurse can provide for the client
      who self-harms and it describes important steps toward recovery--a respectful
      human encounter, understanding, support for the person's efforts in coping,
      optimism and hope that pain will lessen and recovery will take place.

PMID- 14649519
TI  - Australian sexual health nurses: variations in practice.
AB  - OBJECTIVES: The study aimed to describe the scope of practice of Australian
      Sexual Health Nurses in order to inform development of nationally consistent role
      functions. METHOD: Descriptive cross sectional survey of 201 sexual health nurses
      utilising an anonymous self-administered questionnaire with reply paid envelope
      which was sent to members of the Australian Sexual Health Nurses Association
      along with a letter which encouraged them to ask non member sexual health nurses
      to also complete a questionnaire. MAJOR FINDINGS: Despite the fact that most
      Australian Sexual Health Nurses are employed in sexual health centres and family
      planning clinics, this study showed the scope of their practice to be extremely
      varied both in and between states/territories. CONCLUSION: The scope of practice
      of Australian sexual health nurses is varied. While questions remain as to the
      reasons for difference, the authors argue that the specialty needs to work toward
      a national model for basic sexual health nursing care. It is recommended that
      this model be based on knowledge of and rationales for variations in practice.

PMID- 14649521
TI  - Transcultural nursing and challenging the status quo.

PMID- 14649520
TI  - Recovery from disordered eating: what life histories reveal.
AB  - There are few studies seeking to understand the illness from the experiential
      perspective of a person who has recovered from an eating disorder. The clinical
      and research literature shows inconsistencies and varying degrees of support for
      the risk factors associated with eating disordered behaviour. It is important to
      note, however, that most contemporary research relies upon brief self-report
      questionnaires, which may be providing a fragmented picture of the behaviour. The
      focus of the current study is to gain a greater understanding of women's
      perceptions of developing, living with and recovering from an eating disorder.
      This study reports interviews with five former eating disorder sufferers who were
      recruited via an advertisement placed in an Eating Disorders Support Network
      newsletter. Life histories were gathered from each woman and the paper reports
      how these women perceive the origins of their illness and what event(s) lead to
      their recovery. Participants' narratives were analysed to elucidate themes
      pertaining to the lived experience of illness and recovery. The women talk about
      a lack of control of their lives and unrealistic family expectations as reasons
      for the development of their eating disordered behaviour. Recovery was very
      strongly related to self-determination and self-acceptance. Suggestions
      concerning new ways of conceptualising recovery from eating disordered behaviour
      are posited.

PMID- 14649522
TI  - Globalisation as we enter the 21st century: reflections and directions for
      nursing education, science, research and clinical practice.
AB  - The events of September 11th, 2001 in the United States and the Bali bombings of
      October 2002 are chastening examples of the entangled web of the religious,
      political, health, cultural and economic forces we experience living in a global
      community. To view these forces as independent, singular, linearly deterministic
      entities of globalisation is irrational and illogical. Understanding the concept
      of globalisation has significant implications not only for world health and
      international politics, but also the health of individuals. Depending on an
      individual's political stance and world-view, globalisation may be perceived as
      an emancipatory force, having the potential to bridge the chasm between rich and
      poor or, in stark contrast, the very essence of the divide. It is important that
      nurses appreciate that globalisation does not pertain solely to the realms of
      economic theory and world politics, but also that it impacts on our daily nursing
      practice and the welfare of our patients. Globalisation and the closer
      interactions of human activity that result, have implications for international
      governance, policy and theory development as well as nursing education, research
      and clinical practice. Nurses, individually and collectively, have the political
      power and social consciousness to influence the forces of globalisation to
      improve health for all. This paper defines and discusses globalisation in today's
      world and its implications for contemporary nursing education, science, research
      and clinical practice.

PMID- 14649523
TI  - Meeting diversity challenges: pathway of 'advanced' transcultural nursing
      practice in Australia.
AB  - This paper aims to address the state of transcultural nursing in Australia. In an
      attempt to address the challenges of cultural diversity in nursing practice, the
      significance of research-based transcultural nursing knowledge is examined within
      the evolutionary changes of multicultural policies in Australia. Transcultural
      nursing research, building upon existing nursing knowledge, provides evidence to
      advance transcultural nursing practice. In order to promote 'adanced practice' in
      multicultural Australia, models of research-based transcultural nursing practice
      are examined and highlighted.

PMID- 14649524
TI  - A study of clinical nursing research priorities in aged care: a Hong Kong
      perspective.
AB  - The aim of this study was to identify clinical research priorities in aged care
      from the perspectives of rehabilitation aged care nurses in Hong Kong. The Delphi
      method was used whereby 33 registered nurses working in an aged care
      rehabilitation ward identified 28 research questions pertaining to areas in which
      nurses could take a leadership role: clinical research that is of highest value
      to patients and nurse specialists; clinical research which would provide improved
      community care; facilitate health promotion and disease prevention and be of
      value to the professional needs of clinical nurses. Study findings have
      implications and provide direction for clinical nursing research in aged care.

PMID- 14649525
TI  - Critical thinking integration into nursing education and practice in Japan: views
      on its reception from foreign-trained Japanese nursing educators.
AB  - The development of critical thinking (CT) abilities for clinical practices is a
      current emphasis in nursing education and practice in Japan. Through informal
      discussion with foreign educated Japanese nurses who had learnt CT, the expressed
      concern was that the educational concepts focusing on the development of CT
      skills do not appear to be successfully implemented into nursing curriculum of
      many faculties in Japan. The main focus of this study is to explore the views of
      foreign educated Japanese nursing educators on the receptivity of an alternative
      approach to integrate CT into nursing education and practice in Japan. Relevant
      literature on Japanese nursing practice and education is reviewed as it provides
      a background for the study and highlights potential influences concerning the
      participants. Heideggerian phenomenology and interpretive methods to analyse semi
      structured interviews provided the analytic basis for the study. Analysis of data
      revealed that participants' main concerns were the lack of integration of CT
      teaching and learning approaches for the development of CT abilities into the
      current milieu of Japanese nursing education and practice. The reasons for the
      participants' concerns have been related to the influence of cultural and
      educational values shaping contemporary nursing education approaches and
      practices. The outcomes of this study propose how these values reverberate
      through teaching, learning and practice methods.

PMID- 14649526
TI  - The impact of migration on health beliefs and behaviours: the case of Ethiopian
      refugees in the UK.
AB  - The Research Centre for Transcultural Studies in Health, Middlesex University and
      the Ethiopian Community Centre in the UK conducted a study to explore the
      migration experiences of Ethiopian refugees in the UK and the impact of this on
      their health beliefs and behaviours. Data was collected via: i) semi-structured
      interviews were conducted with Ethiopians refugees and asylum seekers and
      Ethiopian professionals providing services for Ethiopian refugees; ii) a semi
      structured questionnaire; iii) a documentary analysis of newspaper articles
      concerning refugees; and iv) an ethnohistory of Ethiopia. The findings revealed
      that Ethiopian refugees place a stronger emphasis on externalised factors
      influencing health (such as happiness and good social relations) than they did in
      Ethiopia. The study found that participants fled Ethiopia due to oppression,
      violence, fear and poverty; and once in the UK experience poor housing,
      unemployment, racism and isolation, all of which impact on their health status.
      Whilst it is difficult to ascertain how these factors affect health beliefs it is
      probable that these negative experiences and the consequent unhappiness they have
      caused have highlighted to them the relationship between health and subjective
      well-being, something that people who have not suffered such life traumas may
      take for granted. In the UK Ethiopian refugees are more likely to seek Western
      medicine than they did in Ethiopia, which reflects both acculturation and
      differences in health resources. This study highlights that Ethiopian refugees,
      require holistic health care that addresses all their needs--physical, mental,
      spiritual, environmental and social-cultural. Nurses should understand that many
      refugees have had traumatic experiences and continue to live in desperate
      circumstances. Thus nurses should be aware of the experiences, needs and beliefs
      of refugees and address their own cultural competence.

PMID- 14649527
TI  - Nursing people from cultures other than one's own: a perspective from New
      Zealand.
AB  - Nursing a person from another culture is a dynamic, complex and tension-filled
      phenomenon. It is also always culturally and historically situated. This paper
      provides an overview of the evolving meaning of 'culture' in New Zealand nursing.
      Then, drawing upon the findings of research that used hermeneutic phenomenology
      to explore the experience of nursing people from cultures other than one's own, a
      description of the constituent parts is of this phenomenon is briefly outlined
      and followed by an exemplar that describes the coalescent and contradictory
      nature of the phenomenon as a whole. As New Zealand nurses negotiate the
      conflicts essential for ongoing development of their practice, interplay of the
      notions of prejudice, paradox and possibility is evident at intrapersonal and
      interpersonal levels as well as in relation to professional and other discourses.

PMID- 14649528
TI  - The nurse's role in improving indigenous health.
AB  - The health status of indigenous peoples is a global concern with mortality and
      hospitalisation data indicating that the health of indigenous groups falls below
      that of other ethnic groups within their countries. The preliminary findings of
      grounded theory research project undertaken with a group of 23 New Zealand Maori
      women about their health priorities and 'mainstream' health service needs provide
      the foundation for an exploration of issues impacting on the health status of
      indigenous people. The role that nursing and nurses have in improving access and
      use of health services by indigenous people will be discussed. Strategies are
      suggested that nurses can utilise within their practice when working with local
      indigenous groups.

PMID- 14649529
TI  - Co-operative inquiry: the development of a visual impairment prevention program
      initiative for two Aboriginal communities in South Australia.
AB  - Impaired vision and blindness are two serious health problems in Australian
      Aboriginals. In an initiative known as the Visual Impairment Prevention Program
      (VIPP) commonwealth funding was made available to each state/territory to improve
      eye status of the Aboriginal population. The South Australian Department of Human
      Services selected two Aboriginal communities to take part in this initiative.
      This paper outlines how Flinders University participated in this process. The aim
      was to conduct an eye program for Aboriginal health workers and develop eye
      health promotional resources for educational use in the Aboriginal community. The
      principles of Co-Operative Inquiry were used to guide the process. An evaluation
      indicated that both products were culturally acceptable to the Aboriginal
      community.

PMID- 14649530
TI  - Transmission of health knowledge and health practices from men to boys among
      Aboriginal communities and non-Indigenous Australians: searching for evidence.
AB  - Although men's health literature has developed rapidly over the last decade and
      covers a plethora of issues, almost no attention has been paid to understanding
      the transmission of health knowledge from men to boys in Australian society. This
      paper identifies a paucity of literature on the topic and offers explanations for
      this phenomenon. To raise awareness among health professionals of the need to
      explore the topic, the authors outline literature pertaining to men's role within
      the family and gender specfic cultural practices. This information is combined
      with the authors' personal experiences with Indigenous and non-Indigenous
      Australian men to provide a background to this emerging issue.

PMID- 14649531
TI  - Testing Orem's Self-Care Agency and Basic Conditioning Factors in a Chinese
      community undergoing haemodialysis.
AB  - This paper reports results of tests of Orem's Self-Care Agency and Basic
      Conditioning Factors in a Chinese community undergoing haemodialysis measured by
      the modified Chinese version of the ASA scale. Eighty-six patients from one major
      city of China, Tianjin, all of whom had end stage renal disease and were
      undergoing haemodialysis formed the sample of the study. The research instrument
      employed in the study was the modified version of the Appraisal of Self-care
      Agency Scale, developed for use with patients undergoing haemodialysis. The
      levels of self-care agency of the patients were identified with respect to the
      findings of the study. The relationships between the self-care agency and basic
      conditioning factors were investigated by the use of Spearman Rank Correlation
      Coefficients and the relationships were statistically supported by the findings
      of this research.

PMID- 14649532
TI  - Coronary heart disease in Indians: a review of literature.
AB  - A literature review utilising literary databases, World Wide Web and hand
      checking of written articles was conducted to determine the magnitude of the
      problem of coronary heart disease (CHD) in Indians with a particular emphasis on
      those in Australia. Health care professionals need to be aware that Indians have
      a higher than average risk of CHD at an earlier age and poorer survival and this
      is impacted on by genetic, social and cultural factors. The experiences of
      Indians with CHD needs to be researched so that prevention and rehabilitation
      programs can be individualised for this well developed community group in
      Australia.

PMID- 14649533
TI  - The first 12 weeks following discharge from hospital: the experience of Gujarati
      South Asian survivors of acute myocardial infarction and their families.
AB  - The period following discharge from hospital after an acute myocardial infarction
      (MI) is associated with vulnerability and psychosocial and physical morbidity for
      many survivors and their families. It is reported that people experience
      interpersonal, family and financial problems, self-care obstacles, work and
      physical difficulties. Culture and ethnicity undeniably influence the illness
      experience and the process of recovery and adjustment. This study investigated
      the perceptions of Gujarati survivors of acute MI and their families in
      Leicester, United Kingdom in the first 12 weeks following discharge in order to
      develop a profile of their health seeking beliefs and needs. Thirty-one
      interviews with 19 Gujarati MI survivors and their families (representing
      approximately 31 hours of dialogue) were analysed using grounded theory.
      Qualitative data revealed a period of vulnerability not only for survivors but
      also their families as they processed recent events and faced the future. Data
      analysis revealed nine interrelated themes describing the post-discharge
      experience for Gujarati survivors and their families. Data revealed that normal
      life was often markedly changed by the MI experience. Reflection, contemplation
      and resignation characterize this period of vulnerability. Overwhelmingly, data
      analysis revealed that the Gujarati culture, beliefs and customs influenced the
      recovery experience.

PMID- 14649534
TI  - Coronary heart disease in Aboriginal communities: towards a model for self
      management.
AB  - Coronary heart disease (CHD) is one of the main causes of death and disability in
      the Aboriginal population, and is the major cause of the twenty-year gap in life
      expectancy of Aboriginal and non-Aboriginal Australians. This paper explores
      Aboriginal health in relation to CHD, and suggests self-management as a
      culturally acceptable therapeutic and sustainable ideology from which positive
      outcomes may be achieved.

PMID- 14649535
TI  - The effects of education on anxiety among Chinese patients with heart disease
      undergoing cardiac catheterization in Hong Kong.
AB  - OBJECTIVE: To examine the effects of patient education on anxiety among Chinese
      patients with heart disease undergoing cardiac catheterization in Hong Kong.
      DESIGN: Randomized experimental design, data collected on three occasions from
      subjects. SETTING: A regional major hospital in Hong Kong. SUBJECTS: 62 clients
      who met the inclusion criteria were randomly allocated into experimental and
      control groups with 31 subjects in each group. INTERVENTION: Group education
      before cardiac catheterization. MAIN OUTCOME MEASURES: State Anxiety Inventory
      (STAI Form Y-1) and Knowledge about Cardiac Catheterization. RESULTS: State
      anxiety of all subjects reached the highest at the time just before cardiac
      catheterization and recorded the lowest at the time following the procedure. A
      lower level of anxiety was experienced by the experimental subjects who received
      the education intervention when compared with the control subjects who did not
      receive the education intervention before cardiac catheterization. CONCLUSION:
      The study provides initial information about anxiety reduction with education
      intervention among Chinese heart disease patients undergoing cardiac
      catheterization. It is envisaged that the study may also assist health
      professionals in developing and designing effective educational programmes for
      clients prior to cardiac catheterization.

PMID- 14649536
TI  - Assessment of inpatient treatment of mentally ill patients in Thailand:
      implications for practice.
AB  - Given the demand for services, psychiatric facilities in Thailand, strive to
      provide quality care despite limited resources. Patient quality of care
      initiatives are limited. The purpose of this investigation is to assess the
      quality of inpatient treatment among a group of acutely mentally ill hospitalized
      Thai patients. This study presents important data on the standards of care
      provided to mentally ill patients at one inpatient facility in Thailand. This
      study is one of the first to look at the inpatient care for Thais with a
      diagnosis of an acute mental illness. Areas for improvement identfied in this
      research include master treatment planning and documentation of care, patient
      teaching, and management of aggressive behavior. This study provides an insight
      into the patient profile and major nursing problems facing Thai nurses. The
      article also highlights areas of concern such as the high use of ECT and
      mechanical restraint. How pervasive these deficiencies are in other settings is
      not known. The findings in this study were shared with the professional staff. It
      is hope that the nursing staff armed with the results of this study will develop
      performance improvement activities to improve the quality of care.

PMID- 14649537
TI  - Nurse faculty perceptions regarding psychiatric-mental health nursing behavioral
      interventions: a cross-cultural comparison.
AB  - Mental disorders are internationally responsible for significant disease burden
      and disability. However, limited cross-culturally comparisons, related to
      psychiatric-mental health nurses and the care they deliver, have been conducted.
      Therefore, the purpose of this article is to present information obtained from
      nurse faculty from Australia, Hong Kong, Japan, South Korea, Thailand and the USA
      (State of Hawaii) about: a) titles and educational preparation of the psychiatric
      mental health nurses; b) the role and perception of others about the psychiatric
      mental health nurses; c) nursing behavioral interventions, including medications;
      d) length of stay of hospitalized psychiatric patients; e) leading mental health
      problems; and, f) the profile of the population with a mental illness. The
      findings reflect diversity in the role and educational preparation of psychiatric
      mental health nurses, as well as how psychiatric-mental health patients are
      treated.

PMID- 14649538
TI  - Culture, health and social justice.

PMID- 14649539
TI  - Microscope in orbit calibration procedure for a test of the equivalence principle
      at 10(-15).
AB  - The scientific objectives of the MICROSCOPE space mission impose a very fine
      calibration of the on-board accelerometers. However the required performance
      cannot be achieved on ground because of the presence of high disturbing sources.
      On-board the CHAMP satellite, accelerometers similar in the concept to the
      MICROSCOPE instrument, have already flown and analysis of the provided data then
      allowed to characterise the vibration environment at low altitude as well as the
      fluctuation of the drag. The requirements of the in-orbit calibration procedure
      for the MICROSCOPE instrument are demonstrated by modelling the expected applied
      acceleration signals with the developed analytic model of the mission. The
      proposed approach exploits the drag-free system of the satellite and the
      sensitivity of the accelerometers. A specific simulator of the attitude control
      system of the satellite has been developed and tests of the proposed solution are
      performed using nominal conditions or disturbing conditions as observed during
      the CHAMP mission.

PMID- 14649541
TI  - Effect of 3-fluorothalidomide and 3-methylthalidomide enantiomers on tumor
      necrosis factor production and antitumor responses to the antivascular agent 5,6
      dimethylxanthenone-4-acetic acid (DMXAA).
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is an antivascular drug that induces
      tumor necrosis factor (TNF) in mice. Thalidomide inhibits TNF induction by DMXAA
      and also potentiates its antitumor activity. We investigated whether these
      effects were enantiomer specific, using the R- or S-enantiomers of two
      nonracemizable thalidomide analogues. Racemic 3-fluorothalidomide (3FThal) and
      racemic 3-methylthalidomide (3MeThal) were separated into enantiomers of greater
      than 98% optical purity using preparative chiral column chromatography. C57Bl/6
      mice implanted with subcutaneous Colon 38 tumors were treated with DMXAA (25
      mg/kg) alone or together with the pure R- or S-enantiomers by a single i.p.
      injection. TNF levels in the serum or tumor tissues 3 h after treatment were
      measured using ELISAs and tumor growth was also measured. 3FThal and 3MeThal, at
      their respective single maximum tolerated doses (MTD) of 15 and 50 mg/kg, were
      more toxic in mice than thalidomide (100 mg/kg). The R- and S-enantiomers of
      either 3FThal or 3MeThal, at their respective MTD, inhibited DMXAA-induced TNF
      activity in serum and tumor tissue, but no significant differences were observed
      between the enantiomers. Coadministration of racemic or enantiomers of 3FThal or
      3MeThal at their respective MTD did not potentiate the antitumor responses above
      that obtained with DMXAA alone, and no enantioselectivity was apparent. We
      conclude that there is no advantage in using the nonracemizable thalidomide
      analogues to improve the antitumor activity of DMXAA.

PMID- 14649540
TI  - Frequent alterations of Smad signaling in human head and neck squamous cell
      carcinomas: a tissue microarray analysis.
AB  - Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most frequent
      cancer worldwide. HNSCC cell lines are typically refractory to transforming
      growth factor-beta (TGF-beta)-mediated cell cycle arrest. A number of these cell
      lines carry inactivating mutations of the TGF-beta type II (TbetaR-II) receptor,
      and fail to phosphorylate receptor-associated Smads, Smad2 and Smad3. In
      addition, we identified several intragenic mutations of the TbetaR-I gene in a
      small series of metastatic HNSCC specimens, suggesting that disruptions of TGF
      beta signaling might contribute to the development and progression of HNSCC. To
      test this idea, we have now embarked on a larger scale analysis of the patterns
      of expression and activation of Smads in 170 HNSCC specimens assembled in tissue
      microarrays. Smad2 protein was expressed by 99% (95% CI: 96-100%) of tumors. The
      activated form of Smad2, pSmad2, was expressed in 86% (95% CI: 80-91%) of HNSCC,
      indicating their ability to survive and proliferate in spite of the presence of
      bioactive TGF-beta within the tissue microenvironment. In the 24 remaining cases
      (14%; 95% CI: 9-20%), pSmad2 was not detected in the tumor cells, although it was
      expressed by surrounding stromal cells and capillaries. In addition, 38 tumors
      (22%; 95% CI: 16-29%) failed to express Smad4 protein. Thus, we found evidence of
      loss of TGF-beta/Smad signaling in approximately 15-20% of HNSCC specimens, which
      is consistent with the phenotype of established human SCC lines. Moreover, we
      found that these Smad signaling defects were associated with a greater tendency
      for metastatic spread and regional or distant recurrence of HNSCC. These results
      indicate that inactivation of TGF-beta/Smad signaling occurs frequently in HNSCC
      and might have an adverse effect on patient outcome.

PMID- 14649542
TI  - Epidermal growth factor-responsive laryngeal squamous cancer cell line Hep2 is
      more sensitive than unresponsive CO-K3 one to quercetin and tamoxifen apoptotic
      effects.
AB  - Epidermal growth factor receptor (EGFR) plays a role in laryngeal squamous cell
      carcinoma (SCC) development and progression. The flavonoid quercetin (Q) and the
      antiestrogen tamoxifen (TAM) inhibit proliferation of both primary laryngeal SCC
      and laryngeal carcinoma cell lines, through still uncharacterized mechanisms. We
      studied Q and TAM inhibitory effect on epidermal growth factor (EGF)-stimulated
      Hep2 and CO-K3 laryngeal squamous cell lines. Q and TAM (0.1-1.0 microM) induced
      more apoptosis in EGF growth-stimulated than in unstimulated Hep2 cells. EGF
      neither stimulated CO-K3 cell growth nor enhanced Q and TAM-induced apoptosis.
      Mitogen-activated protein kinase (MAPK) analysis revealed that in Hep2 cells, but
      not in CO-K3 cells, EGF induced a time-dependent phosphorylation of p42, p44,
      p38, and p46. In Hep2 cells, but not in CO-K3 cells, Q and TAM produced, upon EGF
      treatment, a twofold increase of p38 and p46 and an enhancement of p42 and p44
      dephosphorylation, suggesting a requirement of EGFR. The enhancing effect was due
      to a p38 and p46 dephosphorylation delayed kinetics. An antiphosphorylated p38
      antibody prevented Q and TAM inhibitory effect on p42 and p44 phosphorylations,
      suggesting that the EGF-dependent increase in Q and TAM apoptotic effect on Hep2
      cells could depend on the p38 inhibition of the survival kinases p42 and p44. In
      SCC, EGFR overexpression is an early event from dysplasia to neoplasia. We
      conclude that the capacity of Q and TAM to increase apoptosis in EGFR-activated
      cells makes these compounds possible chemopreventive drugs in subjects at risk of
      developing laryngeal cancer.

PMID- 14649543
TI  - Reduction of bladder cancer cell growth in response to hCGbeta CTP37 vaccinated
      mouse serum.
AB  - The free beta-subunit of human chorionic gonadotrophin (hCGbeta) is well
      established as an ectopic product of epithelial tumors. Originally explained as
      an epi-phenomenon, hCGbeta production by many types of carcinoma is increasingly
      regarded as a significant tumor event. Studies in bladder cancer have shown that
      hCGbeta production, while not diagnostic, is a very good indicator for poor
      prognosis through correlations with resistance to radiotherapy and rapid
      metastasis. These clinical findings led to in vitro studies that have shown a
      direct response to hCGbeta by bladder carcinoma cell lines. This response is
      linked by inhibition of apoptosis to an increase in cell population. More
      recently, studies on hCGbeta as a marker for poor prognosis in other epithelial
      cancers now suggest that this phenomenon may not be restricted to bladder
      carcinoma. Thus, ectopic hCGbeta represents an ideal target for immunodepletive
      therapy. Antisera were generated from mice vaccinated with full-length hCGbeta
      carboxy terminal peptide (CTP37) and a truncated region comprising 24 of the
      amino acids of the CTP (CTP24), expressed on the surface of cowpea mosaic virus
      (CPMV). The effect of the resultant murine antiseras on bladder carcinoma cell
      growth in vitro was investigated. When CTP37 antisera, at dilutions of 1:50 and
      1:100, were incubated with two hCGbeta-producing cell lines, SCaBER and RT112,
      significant reductions in cell number, up to 43%, were observed. In the bladder
      cancer cell line T24, which does not produce hCGbeta, CTP37 antisera had no
      growth effects. CTP24 antiserum, like control sera from mice immunized with wild
      type CPMV, had no effects on the in vitro growth of any cell lines. This implies
      that full-length CTP37, but not CTP24, is involved in the oncogenic inhibition of
      apoptosis by hCGbeta. hCGbeta CTP37 vaccines are available as well-tested
      antifertility vaccines in the Third World. They have now been tested on cancer
      patients. This study is the only in vitro evidence that such a vaccine would have
      beneficial antitumor effects via immunodepletion mechanisms. We propose that
      vaccines such as this could be used as an adjuvant therapy in the treatment of
      hCGbeta-producing bladder cancers.

PMID- 14649544
TI  - Characterization of prostate cancer DU145 cells expressing the recombinant
      androgen receptor.
AB  - Prostate cancer (PC) develops as a consequence of abnormal androgenic
      stimulation. Unfortunately, most of the PC cell lines are androgen independent
      (like DU145), or express mutated forms of androgen receptor (AR). We have
      produced and characterized a new stably transfected PC line expressing the AR
      (DU145-AR). Untreated DU145-AR cells showed a lower proliferation rate than mock
      transfected cells, but responded to testosterone treatment. PSA mRNA,
      undetectable in mock DU145 cells, was present and upregulated by testosterone in
      DU145-AR. About 5% of DU 145-AR cells showed modification of morphology and
      enriched of f-actin after testosterone treatment. Moreover, in DU145-AR
      plasminogen activator (PA) activity and secreted urokinase type plasminogen
      activator (uPA) protein were lower than in AR negative cells; again testosterone
      induced PA activity and uPA protein only in DU145-AR. These results indicate
      that, in general, the effects of unactivated AR is to suppress function(s) in
      DU145 cells and the addition of testosterone restores the normal properties
      associated with the untransfected cells. Some of the effects described may thus
      be mediated by a ligand-independent activation of AR in DU145 cells.

PMID- 14649545
TI  - Rett syndrome: from discovery to current interest.

PMID- 14649546
TI  - Clinical variability in Rett syndrome.
AB  - The clinical variability of Rett syndrome, associated with mutations in the MECP2
      gene, varies from classically symptomatic female patients to asymptomatic female
      patients, and male patients who have none of the diagnostic features considered
      pathognomonic of this disease. Multiple factors contribute to this variability.
      In our studies, mutations closer to the amino-terminus, prior to amino acid 255,
      led to severe clinical manifestations, such as inability to walk, severe
      dysphagia, and urinary organic acid abnormalities, compared with mutations toward
      the carboxyl-terminus. However, we found no correlation between severity and
      mutation type (missense versus nonsense). Despite the importance of mutation
      location to clinical severity, the widely varying severity within the same
      mutation suggests that in females, X-chromosome inactivation or other epigenetic
      phenomena also have roles in determining severity. We propose that stages 1 and 2
      of the disease are a consequence of failed, time-linked, postnatal expression of
      MeCP2 in cerebellar neurons. This, in association with glutamate N-methyl-D
      aspartate receptor-mediated neuroexcitotoxic injury to the differentiating
      neurons, results in the transient age-specific autistic-like behavior, motor, and
      cognitive dysfunction associated with these stages.

PMID- 14649547
TI  - MECP2 and beyond: phenotype-genotype correlations in Rett syndrome.
AB  - The association of Rett syndrome with pathogenic mutations of the methyl-CpG
      binding protein 2 (MECP2) gene was first made in 1999. Since that time, it has
      been found that the clinical phenotype can, at least in part, be explained in
      terms of the type and location of the MECP2 mutation and epigenetic factors such
      as skewing of X-chromosome inactivation. In addition, MECP2 mutations may be
      associated with non-Rett syndrome clinical phenotypes, including nonsyndromic and
      syndromic X-linked mental retardation and Angelman-like phenotypes. Intense
      research efforts are currently focused on understanding the pathogenesis of Rett
      syndrome, using sophisticated techniques such as microarray analysis, and the
      development of mouse models, with an ultimate aim being the development of
      targeted therapies that could ameliorate or even prevent the devastating
      consequences of this enigmatic neurodevelopmental disorder.

PMID- 14649548
TI  - MeCP2 expression in human cerebral cortex and lymphoid cells: immunochemical
      characterization of a novel higher-molecular-weight form.
AB  - Most cases of Rett syndrome are associated with mutations in the coding region of
      MECP2. Here we characterized a novel MeCP2 immunoreactivity, initially detected
      in normal cerebral cortex, by using a panel of MeCP2 antibodies and a combination
      of immunochemical techniques. We found that a novel higher-molecular-weight form
      (approximately 100 kDa) of MeCP2 is detected in human frontal cortex nuclear and
      synaptic fractions and in lymphoid cells. Although in the cortex the higher
      molecular-weight form is relatively more abundant than the standard approximately
      75 kDa immunoreactivity, in extranuclear locations, lymphocyte lysates show a
      predominance of the standard 75 kDa band. Lymphoblasts revealed a more complex
      pattern of MeCP2 expression, with prominent higher-molecular-weight form and both
      higher-molecular-weight form and 75 kDa MeCP2 immunoreactivities encompassing
      several closely migrating bands. We also successfully immunoprecipitated both the
      75 kDa immunoreactivity and the higher-molecular-weight form MeCP2 from cerebral
      cortex with a C-terminal antibody and confirmed their identities by
      immunoblotting with C- and N-terminal antibodies. Our data provide compelling
      evidence for the existence of a novel MeCP2 molecular form, most likely the
      result of post-translational modification. Detection in both brain and lymphoid
      cells suggests an important role for higher-molecular-weight form in MeCP2
      dependent processes. The presence of higher-molecular-weight form MeCP2 in
      postsynaptic fractions indicates a possible involvement in linking synaptic
      activity and transcriptional repression that, in turn, could play a role in the
      pathogenesis of Rett syndrome and other neurologic disorders.

PMID- 14649549
TI  - Survey of MeCP2 in the Rett syndrome and the non-Rett syndrome brain.
AB  - The clinical and neuropathologic aspects of Rett syndrome suggest that an arrest
      of brain development produces the phenotype, but it is not understood how the
      gene implicated in Rett syndrome, methyl-CpG protein 2 (MeCP2), is regulated
      during brain development. In this study, the ontogeny of MeCP2 is examined in the
      developing human brain and in the female Rett syndrome brain to evaluate the
      relationship between MeCP2 expression and brain development in health and
      disease, respectively. Immunocytochemistry using an antibody to the C-terminal
      region of the protein was performed in paraffin sections of the developing brain
      to define the age and the sites of MeCP2 protein expression. In development,
      there is no MeCP2 expression in the germinal matrix or in the progenitor cells.
      At 10 to 14 weeks' gestation, the neurons of the brain stem and the Cajal-Retzius
      and subplate neurons of the cortex express MeCP2. By midgestation, some neurons
      of the basal ganglia express MeCP2, and at late gestation, the most mature
      cortical neurons in the lower cortical layers are positive. The postnatal cortex
      continues to increase its expression of neuronal MeCP2. In the Rett syndrome
      brain, fewer neurons express MeCP2 than in the normal brain. This reduction is
      most apparent in the brain stem and thalamus. The neurons of the cerebral cortex
      show the least reduction. We conclude that the regulation of MeCP2 abundance is
      related to human brain development, being expressed in neurons when they appear
      mature. In Rett syndrome, however, the expression pattern of MeCP2 does not
      completely resemble that of the normal immature brain, suggesting that the
      maintenance of MeCP2 might be determined in specific neurons by factors other
      than those controlling maturation. In the developing brain, synaptic activity and
      plasticity could be necessary to maintain MeCP2 in selected neuronal populations.

PMID- 14649550
TI  - Neurobiology of Rett syndrome.
AB  - Girls with Rett syndrome display signs of neuronal dysfunction including mental
      retardation, seizures, stereotyped movements, and abnormal breathing and
      autonomic control. Decelerating head growth during infancy might reflect a
      disorder in production or pruning of neuronal synapses or both. Recent
      immunocytochemical studies in rodent brain investigating development of MeCP2,
      the transcription factor mutated in Rett syndrome, suggest that expression is
      delayed until the time of synapse formation. These findings are consistent with
      other evidence that Rett syndrome disrupts genetic programs that establish and
      refine synaptic connections.

PMID- 14649551
TI  - Neurotrophic factors in the pathogenesis of Rett syndrome.
AB  - Rett syndrome is characterized by disruption of a period of vigorous brain growth
      with synapse development. Neurotrophic factors are important regulators of
      neuronal growth, differentiation, and survival during early brain development.
      The aims of this study were to study the role of neurotrophic factors in Rett
      syndrome, specifically whether Rett syndrome has abnormal levels of specific
      neurotrophic factors in serum and cerebrospinal fluid and whether the changes
      differ from other neuropediatric patients, for example, those with infantile
      autism. Four neurotrophic factors were measured: nerve growth factor, brain
      derived neurotrophic factor, glial cell line-derived neurotrophic factor, and
      insulin-like growth factor 1 from the frozen cerebrospinal fluid and from serum
      (except glial cell line-derived neurotrophic factor) by enzyme-linked
      immunosorbent assay and cerebrospinal fluid glutamate and aspartate by high
      performance liquid chromatography (HPLC) method in patients with Rett syndrome.
      Insulin-like growth factor 1 was measured from the cerebrospinal fluid of
      patients with infantile autism. We found low concentrations of cerebrospinal
      fluid nerve growth factor in patients with Rett syndrome compared with control
      patients. The serum levels and other cerebrospinal fluid neurotrophic factor
      levels of the patients did not differ from the controls. Patients with Rett
      syndrome had high cerebrospinal fluid glutamate levels. Patients with infantile
      autism had low cerebrospinal fluid insulin-like growth factor 1 levels. Nerve
      growth factor acts especially on cholinergic neurons of the basal forebrain,
      whereas insulin-like growth factor 1 acts on cerebellar neurons. In Rett
      syndrome, the forebrain is more severely affected than the other cortical areas.
      In autism, many studies show hippocampal or cerebellar pathology. Our findings
      are in agreement with the different morphologic and neurochemical findings (brain
      growth, affected brain areas, neurotransmitter metabolism) in the two syndromes.
      Impairment in dendritic development in Rett syndrome could be the consequence of
      cholinergic deficiency and of neurotrophic factor/glutamate imbalance.
      Cholinergic gene expression might be influenced by the Rett syndrome gene
      directly or via the neurotrophic factor system.

PMID- 14649552
TI  - Possible mechanisms of osteopenia in Rett syndrome: bone histomorphometric
      studies.
AB  - The etiology of frequently occurring osteoporosis in Rett syndrome is unknown.
      Five girls, ages 9.75, 11, 12, 13.5, and 14 years, with typical Rett syndrome
      requiring scoliosis surgery presented an opportunity to study bone remodeling by
      quantitative bone histomorphometry. Anterior iliac crest bone biopsies taken 1 to
      2 days after double labeling of the bone surfaces with tetracycline were
      submitted for histomorphometry. Bone volume was reduced, and the surface
      parameters of formation (osteoid surface) were normal, whereas the parameters of
      resorption (osteoclast surface and number) were decreased. In four girls, the
      rate of bone formation was reduced but could not be measured in one girl owing to
      poor labeling. It is possible that the slow rate of bone formation impedes the
      development and accumulation of peak bone mass and contributes to the decreased
      bone volume in Rett syndrome. Perhaps MECP2 mutations in Rett syndrome not only
      influence brain development but also affect bone formation.

PMID- 14649553
TI  - Results of surgery for scoliosis in Rett syndrome.
AB  - The British Isles Survey for Rett Syndrome stores longitudinal health data from
      clinical examinations and postal questionnaires to monitor health and severity in
      Rett syndrome, including the presence and severity of scoliosis and the effects
      of corrective surgery. Scoliosis is rarely present at birth (3% before
      regression) but usually appears by 25 years (87%). The degree tends to increase
      with growth and by 16 to 20 years, 43% (75 of 173) of cases with classic Rett
      syndrome reported severe or operated scoliosis. Surgical correction was reported
      in 91 classic cases. Following initial postoperative recovery, families
      considered that the operation had improved general well-being for 84% of
      individuals (42 of 50 classic cases with postoperative health reports). Thirteen
      of 50 patients walked independently before surgery, and 12 patients did so
      following surgery; 2 stopped walking, and 1 who had not walked began to do so.
      Scoliosis surgery usually benefited sitting posture (82% better, 10% worse),
      chest episodes (52% better, 6% worse), and digestion of food (42% better, 6%
      worse). However, toilet function was improved in only 10% and deteriorated in
      20%. Families reported short-term problems at operation in 48% (24 of 50) and
      minor recurrence of scoliosis in 22% (11 of 50). Surgery in a specialized unit is
      satisfactory management for severe scoliosis in Rett syndrome. Recommendations
      include planning for surgery when the curve passes 40 degrees, ensuring optimal
      nutrition before and after surgery, robust fixture of the whole spine in two
      stages, familiarization of the surgical team with the individual and the disorder
      before the operation, and inclusion of the main carer in the hospital care team.
      Parents form an important part of the management team. Families also require
      support during and after this stressful major procedure.

PMID- 14649554
TI  - InterRett and RettBASE: International Rett Syndrome Association databases for
      Rett syndrome.
AB  - In 2001, the International Rett Syndrome Association funded the establishment of
      a World Wide Web-based database to collect and display the genetic data of
      children and adults with Rett syndrome from around the world. RettBASE
      (<http://mecp2.chw.edu.au>) encompasses both published and unpublished data;
      includes pathogenic mutations, benign polymorphisms, and sequence variations of
      uncertain significance; and has a range of query capabilities, allowing for
      simple or complex interrogation of the database. To undertake genotype-phenotype
      correlations and to identify the likely subtle differences in phenotype, detailed
      phenotype data on large samples will be provided by the International Rett
      Syndrome Association International Phenotype database InterRett. InterRett is
      under development by the Australian Rett syndrome study group at the Telethon
      Institute for Child Health Research in Perth, Western Australia. It will collect
      data from clinicians and families and provide deidentified, collated data on the
      Internet (<http://www.ichr.uwa.edu.au/rett/irsa>). Data records will be linked
      with RettBASE through a common unique identifier. An international reference
      panel is advising on the development of the database. Data collection procedures
      from families and clinicians are currently being piloted. Full data collection
      from both groups began in the second half of 2003. Concurrently, the output
      database will be developed to provide deidentified individual records and
      collated data for clinicians and researchers and collated data for families and
      the general public. This Web-based database will be an invaluable resource for
      understanding the nature of the disorder and managing children and adults with
      Rett syndrome.

PMID- 14649555
TI  - Alternative therapy use by Chinese-Canadian children with stroke and
      cerebrovascular disease.
AB  - The use of alternative therapies in immigrant children with stroke and
      cerebrovascular diseases has not been reported. We identified immigrant and first
      generation Chinese-Canadian children with stroke and cerebrovascular diseases in
      a pediatric stroke clinic and used standardized questionnaires to interview their
      parents about alternative therapy use. The chi-square test was used to assess the
      associations of parental educational level and foreign birth in the child with
      alternative therapy use. We identified 17 children, 9 boys and 8 girls. Six were
      immigrants to Canada and 11 were Canadian born. Nine of 17 families (53%)
      reported using alternative therapies. All 9 used Chinese herbs, but only 3 were
      able to report the names of specific preparations. Four families were using
      medications that had the potential to affect coagulation. Documentation of
      alternative therapy use was found in the medical charts of 3 of the 9 patients.
      Three families reported feeling uncomfortable discussing alternative therapy use
      with their physicians. We did not see an association between alternative therapy
      use and parental educational level or foreign birth in the child. Physicians
      should be aware that parents of children with stroke may be using alternative
      therapies to treat their children and may be unwilling or unable to report all
      therapies used.

PMID- 14649556
TI  - Neurofibromatosis 2 in the pediatric population.
AB  - Neurofibromatosis 2 is a severe autosomal dominant disorder characterized by the
      occurrence of bilateral vestibular schwannomas and other benign tumors of the
      nervous system. Excellent natural history studies exist for adults with
      neurofibromatosis 2, but limited outcome data are available for children with
      neurofibromatosis 2. In this study, we present clinical data on 12 patients with
      neurofibromatosis 2 and age at diagnosis before 18 years. Full record review
      included surgical reports, pathology reports, and imaging studies; all patients
      were personally examined by a single author. One third of the patients presented
      with hearing impairment and another third presented with other cranial nerve
      dysfunction. Tumor load was extensive, including cranial meningiomas in 75%,
      cranial schwannomas other than vestibular schwannomas in 83%, and spinal cord
      tumors in 75%. Family history was present in two thirds of the patients. Surgical
      removal of vestibular schwannomas was performed in 58%; none had full
      preservation of hearing postsurgery. Functionally, 75% of children had hearing
      loss, 83% had visual impairment, 25% had abnormal ambulation, and 25% were
      performing below grade level. In conclusion, increased clinical awareness, better
      imaging techniques, and molecular diagnostics have made pediatric diagnosis of
      neurofibromatosis 2 feasible, but outcomes appear to be worse than in adult
      patients. Further work is needed to determine optimal management of pediatric
      neurofibromatosis 2.

PMID- 14649558
TI  - Pain and palliative care in Costa Rica.

PMID- 14649557
TI  - Encephalocraniocutaneous lipomatosis: neurologic manifestations.
AB  - We report a new case of encephalocraniocutaneous lipomatosis, a rare
      neurocutaneous syndrome of unknown etiology with involvement of tissues arising
      from the mesoderm and ectoderm: skin, eye, adipose tissue, and brain. We also
      review the neurologic manifestations of the syndrome, the most frequent of which
      include seizures, ventricular enlargement, calcifications, mental retardation,
      and cerebellopontine angle tumor. Our patient had an extensive extradural spinal
      cord lipomatous lesion, emphasizing the importance of screening for spinal
      abnormalities in asymptomatic patients with this condition.

PMID- 14649560
TI  - Job satisfaction among hospice interdisciplinary team members.
AB  - The purpose of this study was to investigate job satisfaction among hospice
      interdisciplinary team (IDT) members. Interdisciplinary team members (N = 76)
      from several hospices in Ohio participated in the study. Pearson product-moment
      correlations (p < .05) revealed that there were significant relationships between
      job satisfaction and autonomy, role ambiguity, role conflict, supervisory
      support, task significance, routinization, positive affectivity, negative
      affectivity, and team functioning. Multiple regression analysis (p < .05)
      revealed that supervisory support, positive affectivity, role ambiguity,
      autonomy, and routinization were significant predictors of job satisfaction.

PMID- 14649559
TI  - A palliative medicine program in a community setting: 12 points from the first 12
      months.
AB  - This paper reports the first year's experience of a consultative,
      interdisciplinary, integrated palliative medicine program in a community hospital
      system. Prospective data collection was performed on 308 consecutive
      consultations. A computer database was developed and used to analyze
      demographics, reason for consultation, complexity of medical problems, current
      medications and allergies, physical suffering, spiritual concerns, personal and
      family concerns, consult recommendations, and mortality. In addition, data were
      collected on patient rating of the severity of physical symptoms, pain, spiritual
      suffering, and personal and family suffering; this data also was analyzed using
      the database. Cancer was the most frequent diagnosis (34 percent) and pain the
      most common reason for consultation (43 percent). Population medians were
      identified as follows: five (range, 1 to 10) acute medical problems; three
      (range, 1 to 10) chronic medical problems; and one (range, 0 to 10) medication
      allergy/intolerance. Patients were taking a median of 10 (range, 0 to 29)
      medications, including a median of two analgesics. Eighty percent could
      communicate concerning physical symptoms and had a median of two (range, 0 to 7)
      bothersome symptoms, with pain the most frequent. Fifty percent or fewer could
      rate physical suffering, pain, hope, spiritual suffering, or personal/family
      suffering using a 0 to 10 scale at consultation. Individual patient ratings
      provided over time for physical suffering, pain, hope, spiritual suffering, and
      personal/family suffering were available for less than 25 percent. A median of
      eight recommendations was made for each consultation, with medication changes
      suggested for 84 percent. For those known to have died, the median survival from
      time of consultation to death was 11 days.

PMID- 14649561
TI  - On projective identification, containment, and feeling special: some thoughts
      about hospice nurses' experiences.
AB  - This discussion is derived from a qualitative research study that examined the
      benefits of small group supervision for hospice nurses. Sigmund Freuds beliefs
      about early human development, Melanie Klein's theories of projective
      identification, and the later developments by Wilfred Bion concerning the
      container and contained, form a framework for understanding events. Alternative
      ideas are drawn from early psychoanalytic research with nurses. Individual
      comments from hospice nurses illustrate the profundity of working with issues of
      serious illness, while the work of a hospice nurse is illustrated with a single
      clinical narrative. The discussion poses questions rather than offering answers
      to the complexities of human service. It shows how some people throughout the
      event of serious illness may signal their readiness to make important changes in
      their lives or, conversely, intensify normal unhelpful modes of communicating
      with others. With the support of other members of the team, a hospice nurse was
      able to help a man ill with cancer to decide how to live the brief life that was
      left to him and make closer relationships. Thoughtful work discussions also seem
      to offer much to hospice nursing practices in the way of learning and support.

PMID- 14649562
TI  - The Ohio Hospice Bereavement Study: meeting NHPCO standards.
AB  - Little attention has been paid to documenting the quality and impact of hospice
      bereavement programs. While quality of life, quality of dying, and quality of end
      of-life measures are common indicators of effective clinical service, they are
      not adequate gauges of quality from a bereavement perspective. The National
      Hospice and Palliative Care Organization (NHPCO) published standards for hospice
      and palliative care programs that included a section on bereavement care. Little
      evaluative work has been done to discover whether hospice programs nationwide are
      compliant with these standards. The purpose of this study was to evaluate whether
      hospice programs (n = 32) in the state of Ohio were meeting the NHPCO bereavement
      standards. Findings indicated that the participating hospice programs were 83
      percent compliant at least some of the time.

PMID- 14649564
TI  - Subcutaneous emphysema: an uncommon presentation of enterocutaneous fistula.
AB  - Patients with advanced cancer often develop enterocutaneous fistulae. The
      enterocutaneous fistulae usually develop from gastrointestinal malignancies. We
      describe a case report of a patient with schwannoma of the ovarian cyst wall who
      developed enterocutaneous fistula but presented with subcutaneous emphysema.

PMID- 14649563
TI  - Morphine hyperalgesia: a case report.
AB  - We report a case of a patient with metastatic testicular cancer and intractable
      pain refractory to massive doses of oral, intravenous, and intrathecal (IT)
      opioids supported by analgesic adjuvants. During our efforts to control his pain,
      the patient exhibited opioid-induced hyperalgesia, an uncommon but important
      phenomenon seen with high-dose opioid therapy. With appropriate opioid adjustment
      -in this case reduction of intrathecal morphine dosage by a factor of 100--the
      condition rapidly resolved and the patient became pain-free and remained so until
      his death six weeks later. The keys to identifying this uncommon, but treatable,
      opioid side effect are recognizing it as a possibility when aggressive efforts to
      control pain with high doses of opioids, especially when administered
      neuraxially, are met with increasing pain.

PMID- 14649565
TI  - Assessment of nutritional status and fluid deficits in advanced cancer.
AB  - Malnutrition and cachexia are frequent manifestations of cancer and are major
      contributors to morbidity and mortality. The assessment of nutrition status in
      cancer patients can be easily accomplished. The first step is to record a
      complete medical history and to perform a thorough clinical examination to
      uncover signs of nutritional deficiency. Simple and inexpensive tests are
      available to assess the body composition, such as: anthropometric measurements,
      skinfold thickness, arm muscle circumference and area, and weight and body mass
      index (BMI). Biochemical measurements are also available, such as serum albumin,
      transferring, and prealbumin. Fluid deficit is divided into two categories based
      on pathophysiology (dehydration and volume depletion) and to three subtypes based
      on plasma sodium concentration (hyponatremic, hypernatremic, and isotonic).
      Dehydration (total water deficit, especially intracellular) is always
      hypernatremic, while volume depletion (intravascular water and sodium deficit) is
      either hyponatremic, hypernatremic, or isotonic. There are no clear clinical
      differences among the various categories, but a delay of capillary refill,
      tachycardia, and orthostatic hypotension is more common with volume depletion.
      Careful clinical assessment and laboratory tests, especially serum sodium, are
      the keystones for diagnosis and effective management. Bioelectrical impedance
      (BEI) is an easy way to assess both nutrition status and fluid deficits in
      advanced cancer and should be used more often than it currently is. This article
      reviews the subjective and objective methods of assessing fluid deficit and
      nutrition in advanced cancer.

PMID- 14649566
TI  - Wind of grace.

PMID- 14649567
TI  - Plates, screws, and children: their relationship in craniomaxillofacial trauma.
AB  - The ideal modality for fixation of pediatric craniomaxillofacial fractures
      remains elusive for a number of reasons. Surgeons who manage these injuries have
      replaced wiring techniques with the introduction of some form of reconstructive
      implant. The most commonly used implants are either resorbable or semi-rigid
      titanium. This presentation is a synopsis of the past 30 years of the English
      speaking scientific literature including plastic and reconstructive surgery,
      otolaryngology, head and neck surgery, oral and maxillofacial surgery, pediatric,
      trauma, craniofacial, materials, and biomaterials publications. While no
      consensus on ideal management was observed, various implant treatment options are
      discussed, including their indications, contraindications, considerations, and
      consequences after implant placement.

PMID- 14649568
TI  - An introduction to electromyography: an invited review.
AB  - Electromyography is a complex diagnostic test that is useful in diagnosing many
      neuromuscular and musculoskeletal conditions. Physiatrists and neurologists
      become familiar with this test during their training, while other physicians have
      minimal or no exposure, outside of perhaps some basic physiology lectures. A
      review of the anatomy, physiology, and physics upon which electrodiagnostic
      testing is based and of the various techniques used during a study provides the
      necessary foundation for understanding and using study results. A discussion of
      the conditions for which electrodiagnostic testing is useful, including carpal
      tunnel syndrome, radiculopathy, peripheral neuropathy, and disorders of the
      neuromuscular junction, is included both to review these disorders and to
      encourage appropriate referral for electrodiagnostic study.

PMID- 14649569
TI  - A biomechanical evaluation of the role of labrum on anterior/posterior
      translation of shoulders at different degrees of abduction.
AB  - The objective of the study was to investigate the effects of anterior and
      posterior labrums on the anterior/posterior translations of shoulders. Thirteen
      cadaver shoulders were arthroscopically evaluated and nine were selected based on
      the absence of any pathological findings. These shoulders were tested intact,
      vented and after sequential arthroscpoic incision of the anterior and posterior
      labrums. The anterior/posterior translations were measured in a specially
      designed apparatus. The loads vs. displacement curves were obtained. The loads
      vs. displacement curves of the shoulders before and after labrum incision did not
      show any appreciable differences. Moreover the measured loads at 6 mm
      displacement did not show any statistically significant differences due to labrum
      incision. It was concluded that both anterior and posterior labrum incisions of
      the shoulders did not show any appreciable differences in anterior/posterior
      laxity. An arthroscopic technique was successfully developed to isolate the
      effect of labrum on the shoulder laxity.

PMID- 14649570
TI  - Bioabsorbable screw fixation in coracoclavicular ligament reconstruction.
AB  - The purpose of this study is to evaluate the biomechanical properties of
      stainless steel and bioabsorbable screw fixation of the clavicle to the base of
      the coracoid. Seven matched pairs of fresh frozen shoulders were prepared by
      removing all soft tissue except the acromioclavicular and coracoclavicular
      ligament complexes. The shoulders were randomly selected and fixed with 4.5-mm
      stainless steel (SS) screws, while contralateral shoulders were fixed with 4.5-mm
      poly L-lactic acid polymer (PLLA) screws. Pullout strength, stiffness, and
      elongation to failure were measured using an Instron Mechanical Tester (Model
      4202). The average pullout strength of 720.6 +/- 244.9 N of the metal screws was
      not statistically different (p = 0.089) from that of the biodegradable screws of
      580.4 +/- 188.6 N. The pullout strengths exerted by both these screws exceeded
      the reported strength (500 N) of the intact coracoclavicular complex indicating
      adequate initial pullout strength for coracoclavicular fixation.

PMID- 14649571
TI  - Thromboembolism following total hip replacement.
AB  - Total hip replacement is an operation that is prone to thromboembolic
      complications, with potentially life-threatening consequences. However, the risk
      has declined substantially in the past three decades, reflecting advances in the
      understanding of the pathophysiology of thromboembolism and perioperative
      prophylaxis. The old concept of deciding thromboembolic prophylaxis after the
      completion of surgery is obsolete. In this review, we will concentrate on the
      main preventive measures that the medical and surgical team should implement
      prior to, during, and immediately after surgery.

PMID- 14649572
TI  - Long-term results of a cementless knee prosthesis with a metal-backed patellar
      component: clinical and radiological follow-up with histology from retrieved
      components.
AB  - Aseptic loosening of cemented knee arthroplasties has encouraged development of
      uncemented fixation. The Miller-Galante I (MG I) prosthesis was designed to
      achieve permanent stability through ingrowth into a titanium fiber mesh. Thirty
      five knees in 30 patients with MG I knee replacements have been followed
      clinically and radiologically with a mean follow-up of 12 years. Twenty knees
      were revised with a mean follow-up of 5 years. Patellofemoral problems,
      especially avulsion of the polyethylene from the metal-backed patella and in some
      cases severe metallosis, have been the main reason for revision. Metal-backed
      patellar component should be avoided. In addition, instability has been a
      problem. However, the fixation of the components has been excellent, with a high
      degree of osseous ingrowth displayed at histological analysis of retrieved
      components. The clinical and radiological results after revision are in most
      cases good, despite the femoral component having been left in situ.

PMID- 14649573
TI  - Comparative study of the covered area of Leeds-Keio (LK) artificial ligament and
      radio frequency generated glow discharge treated Leeds-Keio (Bio-LK) ligament
      with synovial cells.
AB  - The Leeds-Keio artificial ligament (LK), which was developed not only as a
      ligament substitute but also as a scaffold for tissue induction in knee ligament
      reconstruction, has been in clinical use since 1982 in Europe and Japan.
      Recently, we have developed radio frequency generated glow discharge (RFGD)
      treated LK ligament (Bio-LK) to expedite the process of tissue induction and its
      maturation. In this study of cell adhesion to the scaffold, we report the
      difference in the covered area with synovial cells when using scaffolds made from
      treated and untreated materials. Plasma clot methods were used in this study. The
      covered area on LK and Bio-LK by cells was stained by 0.1% toluidine blue and
      analyzed using NIH image. The covered area of Bio-LK was about three times higher
      than that of LK (untreated) at 3 weeks. In scanning electron microscopy, more
      cells were observed on fibers of Bio-LK, and these filled the space among the
      fibers more extensively. The spreading of covered area means that cell
      attachment, cell proliferation, and cell migration on the fibers are likely to be
      improved. Our experimental study indicates that Bio-LK will possibly speed up the
      process of induction of autogenous tissue from synovium.

PMID- 14649574
TI  - Outstanding Scientist of 2003: Dr. Zhong Wei Chen, a microsurgery pioneer.

PMID- 14649575
TI  - Minimally invasive surgical management of ureteropelvic junction obstruction:
      laparoscopic and robot-assisted laparoscopic pyeloplasty.
AB  - Ureteropelvic junction (UPJ) obstruction is characterized by a functionally
      significant impairment of urinary transport caused by an intrinsic or extrinsic
      obstruction in the area where the ureter joins the renal pelvis. The majority of
      cases are congenital in origin; however, acquired conditions at the level of the
      ureteropelvic junction may also present with symptoms and signs of obstruction.
      Until recently, open pyeloplasty and endoscopic techniques have been the main
      surgical options, with the intent of complete excision or incision of the
      obstruction. The introduction of laparoscopy and robot-assisted applications has
      allowed for minimally invasive reconstructive surgery that mirrors open surgical
      techniques. These techniques offer substantial benefits to patients by reducing
      morbidity, hastening postoperative recovery, and improving cosmetic outcome.
      During the last decade, laparoscopic pyeloplasty has garnered much interest.
      However, because of the technically challenging nature of this procedure, it is
      performed only at select medical centers by surgeons with advanced laparoscopic
      training. The recent introduction of robotics to the field of minimally invasive
      surgery may facilitate this procedure and allow for more widespread
      implementation by surgeons of varying skill levels. This review is limited
      primarily to the treatment of congenital or acquired UPJ obstruction via
      laparoscopic and robot-assisted laparoscopic pyeloplasty. Herein, we report the
      early results, ongoing evolution, and potential future role for these novel
      surgical procedures.

PMID- 14649576
TI  - Surgical tissue adhesives: new additions to the surgical armamentarium.

PMID- 14649577
TI  - Experience improves successful use of fibrin sealant in total knee arthroplasty:
      implications for surgical education.
AB  - This study evaluating fibrin sealant application in total knee arthroplasty (TKA)
      found significant differences in the decline in adjusted hemoglobin loss at 48
      hours postoperatively in the treatment group (FS) relative to the control group
      (C) when the groups were segregated into early and late subgroups. The decline
      between the late C, 3.53 +/- 0.22 g/dL, and the late FS, 3.01 +/- 0.20 g/dL, was
      0.52 g/dL (p = 0.04). The decline between the early C, 3.51 +/- 0.21 g/dL, and
      the early FS, 3.25 +/- 0.22 g/dL, was 0.26 g/dL (p = 0.34). This study
      demonstrates the importance of experience and education in successful application
      of tissue adhesives.

PMID- 14649578
TI  - Fibrin sealant reduces perioperative blood loss in total hip replacement.
AB  - Patients (n = 81) undergoing total hip replacement (THR) were randomized to
      receive either standard of care plus fibrin sealant (FS) (10 mL total) or
      standard of care alone to evaluate the efficacy of FS for reducing blood loss in
      THR. Considering the 81 intent-to-treat patients, adjusted perioperative blood
      loss was reduced significantly in the FS group, by 197 mL [95% CI: 45 mL, 319 mL]
      or 23.5% [95% CI: 5.4%, 38.1%] (p = 0.014). When protocol violators were
      eliminated, leaving 73 patients, the adjusted FS group perioperative bleeding was
      reduced by 221 mL [95% CI: 63 mL, 351 mL] or 27.1% [95% CI: 7.6%, 42.5%] (p =
      0.0098).

PMID- 14649579
TI  - Presentation of gamma-irradiated-in-air polyethylene wear in the form of a
      synovial cyst.
AB  - The increased wear of polyethylene sterilized with gamma irradiation in air has
      well been documented in the total knee arthroplasty literature. Our case report
      describes a patient with a well-functioning total knee replacement presenting
      with wear debris synovitis in the form of a large synovial cyst. We discuss this
      patient's preoperative evaluation, intraoperative findings, and postoperative
      outcome after synovectomy and polyethylene exchange. We also review the current
      literature on appropriate polyethylene sterilization methods.

PMID- 14649580
TI  - Blunt thoracic aortic injury: old problem and new technology.
AB  - The lethal nature of transmural aortic injuries has remained constant; however,
      both the diagnostic and therapeutic interventional options have improved.
      Although aortography is still the "gold standard" against which all other
      diagnostic modalities are measured, contrast-enhanced spiral thoracic computed
      tomography has emerged as the diagnostic study that could potentially supplant
      aortography. The advent of the fast spiral computed tomography scanners offer
      several advantages, including being less affected by patient motion and volume
      averaging artifacts than the earlier generation CT scanners. The operative has
      broadened from primary repair and interposition prosthetic graft placement (with
      possible use of shunt or roller vs. centrifugal bypass) to the potential
      widespread use of endovascular stents. The Eastern Virginia Medical School (EVMS)
      experience during the first 10-year period (see table below) highlights the
      majority of patients undergoing interposition prosthetic graft placement. There
      was no use of shunts during this period. At the midpoint of the second 10-year
      period (1997-2007), the method of repair is exclusively interposition graft
      placement. The role of endovascular stent insertion in the management of these
      injuries is currently being debated. [table: see text]

PMID- 14649581
TI  - Robotic surgery: an update.
AB  - Minimally invasive surgery techniques have revolutionized surgery. Robotic
      surgery may be the next revolution in surgical technology. Robotics coupled with
      minimally invasive surgery and microscopic surgery provides the potential to do
      more complex and more precise tasks. Robotic surgery offers tremor filtration,
      motion scaling, indexed movements, additional degrees of freedom, and improved
      ergonomics. We explore robotic history, the present surgical technology, the
      current clinical cases and research, and the future of robotics. We will look
      specifically at the birth and progress of our own problem.

PMID- 14649582
TI  - Cutaneous T-cell lymphomas: a review with emphasis on new treatment approaches.
AB  - Primary cutaneous T-cell lymphomas represent a wide variety of non-Hodgkin
      lymphomas that are characterized by a distinct clinical presentation. Advanced
      molecular and biological techniques have enhanced the recognition of cutaneous T
      cell lymphomas. The most common subtypes of cutaneous T-cell lymphomas are the
      epidermotropic variants mycosis fungoides and Sezary syndrome. At present, a
      stage-adjusted therapy is the best concept available, since early aggressive
      treatment options did not improve the prognosis of patients with cutaneous T-cell
      lymphomas. Accurate diagnostic and clinical assessment as well as identification
      of prognostic factors provides a helpful basis for treatment strategies. Current
      medical literature on diagnosis, prognosis, and treatment is reviewed with
      emphasis on new biologic response-modifying treatment options.

PMID- 14649583
TI  - Topical and light-based treatments for actinic keratoses.
AB  - Actinic keratosis is currently believed to be an early stage in the evolution of
      squamous cell carcinoma. Active and intensive treatment of actinic keratosis may
      prevent the formation of invasive squamous cell carcinoma and potential
      metastases. While destructive methods of treatment of actinic keratosis remain
      the gold standard for the eradication of visible and palpable actinic keratoses,
      new medical therapies may accomplish this goal more comfortably and reliably for
      the patient. Newer topical medications, light therapy and photodynamic therapy
      are generating promising results that presage more widespread use in the future.
      These novel therapies for the early treatment of actinic keratosis may be
      administered in combination or serially, with the locus of treatment at any given
      time possibly restricted to a region of affected skin. Treatment of incipient or
      subclinical lesions may mitigate the risk of future squamous cell carcinomas
      lesions. Widespread actinic keratosis constitutes a persistent medical problem
      that requires long-term management. The role of traditional and novel treatments
      in the routine treatment of actinic keratosis will be determined by the efficacy,
      limitations and the practicality of each of these methods in individual patients.
      As the first stage of squamous cell carcinoma, actinic keratosis is worthy of
      prompt evaluation and active treatment.

PMID- 14649584
TI  - Topical and light-based treatments for basal cell carcinoma.
AB  - Nonsurgical methods of treatment providing cure rates approaching those provided
      by surgery offer a significant advantage to patients with basal cell carcinoma
      (BCC) in certain anatomic locations. While intralesional interferon has been used
      to treat BCC with some success, the deliver method requires multiple visits to
      the doctor's office, which makes compliance a challenge for the patient. Initial
      success with light-based therapy of BCC over a decade ago has not evolved to the
      point where it is an effective, widely available treatment. The new class of
      immune response modifiers, represented by topical imiquimod cream, shows promise
      for providing topical treatment of early BCC. It is hoped that further
      developments of the class of drugs will produce an agent with fewer side effects
      and improved efficacy for nodular BCC.

PMID- 14649585
TI  - Management of squamous cell carcinoma in organ transplant recipients.
AB  - The number of skin cancers continues to rise with well over one million cases of
      skin cancer expected in the United States this year. Optimal management depends
      on early detection and treatment. The consequences of skin cancer may be
      particularly devastating in organ transplant recipients. In this article,
      management of squamous cell carcinoma in the organ transplant recipient is
      discussed.

PMID- 14649587
TI  - Antibiotics in cutaneous medicine: an update.
AB  - Antibiotics play a vital role in contemporary cutaneous medicine and surgery.
      They are prescribed more commonly than perhaps any other group of medications
      with the exception of the corticosteroids. This review discusses the major oral
      antibacterial agents used in dermatology today, including the beta-lactams,
      macrolides, tetracyclines, quinolones, sulfonamides, clindamycin, and rifampin.

PMID- 14649586
TI  - Systemic therapies for psoriasis: understanding current and newly emerging
      therapies.
AB  - The treatment of moderate to severe psoriasis is a rapidly expanding area. Recent
      insights into the pathogenesis of this disease as a T-cell mediated process has
      led to a greater understanding of the mechanisms of action of conventional FDA
      approved systemic therapies such as methotrexate, cyclosporine, acitretin, and
      psoralen with ultraviolet A phototherapy. It has also led to the development of
      rationally targeted therapies against key components of the immune process
      critical in the generation of the psoriatic plaque. Safety and efficacy data from
      clinical studies of 4 biologic agents furthest along in their development are
      reviewed. These results are promising, adding to the armamentarium for treating
      this disease.

PMID- 14649588
TI  - Management of leg ulcers.
AB  - Chronic wounds, and venous ulcers in particular, are often managed by
      dermatologists. The first step in the management of any lower extremity
      ulceration is accurate diagnosis. Although there are several basic tenets of good
      wound care that remain static regardless of wound etiology, such as maintaining a
      moist and clean wound healing environment, many of the maneuvers that have been
      shown to improve the chances of healing must be individualized to the wound type.
      Many of the techniques in wound management have not changed over the past
      century: compression remains the cornerstone of venous ulcer management. This
      article summarizes some of the techniques used in the management of these wounds.
      We discuss the evidence for using compression, vitamin and mineral
      supplementation, antibiotic use, growth factors, and other interventions in the
      management of these wounds.

PMID- 14649589
TI  - Psychocutaneous drug therapy.
AB  - Many patients with skin disorders have psychosocial issues associated with their
      chief complaints. New psychotropic agents with superior side effect profiles have
      become available to allow nonpsychiatric physicians to manage psychiatric
      patients safely with psychotropic agents that are effective, simple to
      administer, and well tolerated. Dermatologists who wish to help their patients
      with psychodermatologic conditions can greatly enhance their therapeutic
      armamentarium by becoming familiar with the use of a few selected psychotropic
      agents. This article reviews the current status and future directions of
      psychopharmacology for the 4 major types of psychopathologies encountered in a
      dermatology practice (depression, obsessive-compulsive disorder, anxiety, and
      delusional disorder) with the intent of guiding dermatologists in the choice of a
      psychotropic agent for patients with psychological component to their skin
      disorder.

PMID- 14649590
TI  - Bloom where you are planted.

PMID- 14649591
TI  - Women's decision making about the use of hormonal and nonhormonal remedies for
      the menopausal transition.
AB  - OBJECTIVE: To critically review qualitative research on women's decision making
      about the use of hormonal and nonhormonal remedies for the menopausal transition.
      DATA SOURCES: Computerized searches in CINAHL, MEDLINE, Medscape, and PsychINFO
      databases, using the keywords decision making, hormone therapy, herbal remedies,
      attitude toward hormone therapy, and qualitative research; and ancestral
      bibliographies. STUDY SELECTION: Articles from indexed journals from 1982 to 2001
      in the English language relevant to the keywords were evaluated. Sixteen studies
      met inclusion criteria and were included in the analysis. DATA EXTRACTION: Study
      findings were organized into several categories and compared and contrasted
      across publications and categories. DATA SYNTHESIS: Half of the researchers
      described decision making as a weighing of benefits and risks. Women's
      considerations, beliefs, and values, as well as interaction with the environment,
      were primary influences on the process. CONCLUSIONS: Major gaps in care for
      midlife women were identified. Women need information about the process of
      menopause and the range of available options for menopause management. Nurses can
      play a major role in providing information, counseling, and developing decision
      aids. Women's values and beliefs, cultures, life contexts, and desire for
      involvement in the decision should guide interventions.

PMID- 14649592
TI  - Weekend birth and higher neonatal mortality: a problem of patient acuity or
      quality of care?
AB  - OBJECTIVE: To address the differences in neonatal mortality among births to
      teenage mothers on weekdays and weekends. DESIGN: A retrospective descriptive
      design. Rates of neonatal mortality linked to maternal risk factors, low birth
      weight, gestational age, day of the week of the birth, and ethnicity/race were
      examined. PATIENTS/PARTICIPANTS: The population consisted of all recorded births
      to teenage mothers (< 20 years of age) in Texas in 1999 and 2000 (N = 111,749).
      These births were linked to death certificates for a subset of neonatal deaths
      within the same time period (n = 397). MAIN OUTCOME MEASURES: The outcome of
      interest was any death attributed to conditions originating in the perinatal
      period and recorded as such on the infant death certificate. RESULTS: Neonatal
      mortality was higher among the births on weekends than those during the week.
      Maternal risks and patient acuity levels of mothers and babies were not
      consistently higher on weekends. However, when risk factors were present, weekend
      births were more dangerous for Hispanics than for other ethnic or racial groups.
      CONCLUSIONS: Differences in patient acuity did not satisfactorily explain higher
      neonatal mortality rates on weekends. Thus, quality of care indicators such as
      lower hospital staffing and reduced availability of services on weekends may be
      critical sources of unnecessary neonatal deaths.

PMID- 14649593
TI  - The breastfeeding self-efficacy scale: psychometric assessment of the short form.
AB  - OBJECTIVE: The purpose of this study was to reduce the number of items on the
      original Breastfeeding Self-Efficacy Scale (BSES) and psychometrically assess the
      revised BSES-Short Form (BSES-SF). DESIGN: As part of a longitudinal study,
      participants completed mailed questionnaires at 1, 4, and 8 weeks postpartum.
      SETTING: Health region in British Columbia. PARTICIPANTS: A population-based
      sample of 491 breastfeeding mothers. MAIN OUTCOME MEASURES: BSES, Edinburgh
      Postnatal Depression Scale, Rosenberg Self-Esteem Scale, and Perceived Stress
      Scale. RESULTS: Internal consistency statistics with the original BSES suggested
      item redundancy. As such, 18 items were deleted, using explicit reduction
      criteria. Based on the encouraging reliability analysis of the new 14-item BSES
      SF, construct validity was assessed using principal components factor analysis,
      comparison of contrasted groups, and correlations with measures of similar
      constructs. Support for predictive validity was demonstrated through significant
      mean differences between breastfeeding and bottle feeding mothers at 4 (p < .001)
      and 8 (p < .001) weeks postpartum. Demographic response patterns suggested the
      BSES-SF is a unique tool to identify mothers at risk of prematurely discontinuing
      breastfeeding. CONCLUSIONS: These psychometric results indicate the BSES-SF is an
      excellent measure of breastfeeding self-efficacy and considered ready for
      clinical use to (a) identify breastfeeding mothers at high risk, (b) assess
      breastfeeding behaviors and cognitions to individualize confidence-building
      strategies, and (c) evaluate the effectiveness of various interventions and guide
      program development.

PMID- 14649594
TI  - Infant weight and gestational age effects on thermoneutrality in the home
      environment.
AB  - OBJECTIVE: To describe infant temperature in the home environment and explore
      factors, particularly weight and gestational age at birth, associated with
      maintenance of thermal neutral temperatures in the home. DESIGN: Continuous
      abdominal skin temperature was recorded at 1-minute intervals for a 24-hour
      period in both full-term and preterm infants, using a two-group exploratory
      design. SETTING: Infants were studied in the home environment.
      PATIENTS/PARTICIPANTS: Twenty-four preterm and 16 full-term infants were studied
      at approximately 44 weeks postconceptional age. MAIN OUTCOME MEASURES: Abdominal
      skin temperature was coded as within, over, or under the thermal neutral zone,
      and the percentage of time in these thermal conditions was calculated. RESULTS:
      Regression analysis was conducted, and weight, gestational age, and weight by
      gestational age interaction were found to be statistically significant predictors
      of percent of time over and under the thermal neutral zone. Smaller preterm
      infants were overheated, whereas heavier preterm infants were underheated.
      Smaller full-term infants were underheated, and heavier full-term infants were
      overheated. CONCLUSION: Thermal care of infants in the home may be influenced by
      parental perception of thermal vulnerability relative to weight and gestational
      age at birth.

PMID- 14649596
TI  - Recent research findings on women's health in pregnancy and childbirth: an
      updated annotated bibliography from the National Institute of Nursing Research.

PMID- 14649595
TI  - The loving support breastfeeding campaign: awareness and practices of health care
      providers in Mississippi.
AB  - OBJECTIVES: To evaluate the impact of the national breastfeeding promotion
      campaign, Loving Support Makes Breastfeeding Work, on health care providers in
      Mississippi. DESIGN: Cross-sectional study. SETTING: The Mississippi WIC (Women,
      Infants, and Children) program implemented the national Loving Support project
      for the state. Questionnaires were mailed to all hospitals with obstetric
      services and WIC clinics and to a random sample of one half of the practicing
      pediatricians and one third of the practicing family physicians in the state.
      PARTICIPANTS: Two hundred and two health care providers, including 104 nurses and
      98 physicians, responded to the questionnaire. MAIN OUTCOME MEASURES: Health care
      providers' (a) awareness of the breastfeeding promotion activities in the state;
      (b) changes in practice in providing breastfeeding advice and referrals to
      lactation specialists and for breast pumps; and (c) changes in the management of
      breastfeeding-related problems. RESULTS: A significantly higher proportion of
      nurses than physicians mentioned breastfeeding benefits to mothers, provided
      breastfeeding management advice, and referred mothers for breast pumps and to
      lactation specialists after the campaign. CONCLUSIONS: This study showed the
      positive impact of the campaign on nurses' breastfeeding awareness and practices.
      More efforts are needed to continue breastfeeding outreach activities for health
      care providers.

PMID- 14649597
TI  - Labor and birth today: things have changed.

PMID- 14649598
TI  - Trends and issues in labor induction in the United States: implications for
      clinical practice.
AB  - The labor induction rate is at an all-time high in the United States. Although
      induction of labor is recommended as a therapeutic option only when the benefits
      of expeditious birth outweigh the risks of continuing the pregnancy, a
      "psychosocial indication" has become a common rationale for elective induction in
      the United States. It is unlikely that all women are provided with a complete
      discussion of the cascade of interventions that frequently accompany labor
      induction and the risks of cesarean birth. Although at first glance elective
      labor induction may seem more convenient, an appreciation of the inconvenience of
      the greater rates of interventions, the longer labor and overall hospital stay,
      the higher costs, the additional attention required by the primary health care
      provider when complications occur, and the risk of an adverse outcome for a
      mother or baby after an elective procedure with subsequent litigation should
      cause everyone to exercise caution and reevaluate current practice. Professional
      organizations should take proactive steps to advocate for pregnant women so they
      are fully aware of the risks and benefits. A public campaign to discourage
      elective labor induction for nulliparous women is worth serious consideration.

PMID- 14649599
TI  - Analgesia and anesthesia during labor and birth: implications for mother and
      fetus.
AB  - Labor and birth, although viewed as a normal physiological process, can produce
      significant pain, requiring appropriate pain management. Systemic analgesia and
      regional analgesia/anesthesia have become less common, whereas the use of newer
      neuraxial techniques, with minimal motor blockade, have become more popular. Low-
      and ultra-low-dose epidural analgesia, spinal analgesia, and combination spinal
      epidural analgesia have replaced the once traditional epidural for labor. The
      shift from regional anesthesia during labor, in which the woman became a passive
      participant during the labor and birth, to a collaborative approach for pain
      management, in which the woman becomes an active participant, has resulted in a
      new philosophy of labor analgesia. This article provides a review of the current
      systemic analgesics and regional and neuraxial analgesia/anesthesia techniques
      for pain management in labor and birth. Also addressed are implications for
      perinatal nurses who participate in pain management choices during labor and
      birth.

PMID- 14649600
TI  - A new understanding of the second stage of labor: implications for nursing care.
AB  - A reconceptualization of the second stage of labor is proposed, with an early
      phase of descent and a later phase of active pushing, as the basis for nursing
      care related to direction or support of expectant mother's bearing-down efforts.
      This reconceptualization challenges the rules that have accompanied second stage
      by providing criteria for the obstetric conditions optimal for fetal descent that
      develop during the initial phase of second stage as the fetal head rotates to an
      anterior position and descends to at least a 1+ station. The phase of active
      pushing is accompanied by a decline in fetal pH and should be shortened, not only
      by assisting the woman with effective bearing-down but also by allowing a longer
      early phase of second stage and encouraging the woman to push only when the
      obstetric conditions are optimal.

PMID- 14649601
TI  - Intrapartum emergencies.
AB  - Intrapartum emergencies are challenging to all perinatal nurses because of the
      increased risk of adverse outcomes for the mother and fetus. Perinatal
      emergencies, such as seizures, amniotic fluid embolus, hemorrhage, and uterine
      rupture, create physiological challenges and trigger intrinsic survival
      techniques. The pregnant uterus becomes a vital source of blood volume during
      hypovolemic events because it is not considered a vital organ. The pregnancy
      itself may become burdensome, and birth may occur as an intrinsic maternal
      compensatory mechanism. The resultant fetal hypoxemia may also stress the fetus
      into initiating labor. During extensive oxygen desaturation and decompensation,
      the focus should be on maternal stabilization, which will subsequently enhance
      fetal stabilization. Clinical assessments, critical thinking, decision making,
      and resource allocation must be quick and appropriate to increase the likelihood
      of a positive outcome for the mother, fetus, and neonate.

PMID- 14649602
TI  - How do expert labor nurses view their role?
AB  - OBJECTIVE: To examine how expert perinatal nurses in a nurse-managed labor model
      view their role in caring for mothers during labor and birth. DESIGN: Focus group
      methodology. Data were analyzed using inductive coding methods to gain
      understanding from the perspective of those providing the care. SETTING: Labor
      and birth units in four large Midwestern medical centers. PARTICIPANTS: Fifty
      four expert labor nurses. INCLUSION CRITERIA: 5 years experience in nursing care
      during labor and birth in institutions where nurse-managed labor was the
      predominant practice model. RESULTS: Four common themes related to nursing roles
      were identified. These included knowing the labor process and the intuitive
      nature of nursing care provided by expert labor nurses based on years of
      experience, knowing the woman and letting her body guide labor, advocacy for
      laboring woman, and the autonomous nature of the nurse-managed labor model.
      CONCLUSIONS: Expert labor nurses developed a keen sense of intuitive knowledge
      based on their years of experience. They reported using hands-on high-touch
      supportive care techniques with the potential to affect labor and birth outcomes.
      Autonomy is perceived as a key component of practice within the nurse-managed
      labor model.

PMID- 14649603
TI  - Childhood obesity--a growing epidemic.

PMID- 14649604
TI  - The 2003 Behavior Management Conference--what's at stake?

PMID- 14649605
TI  - Children's first dental visit: attitudes and practices of US pediatricans and
      family physicians.
AB  - PURPOSE: The aim of the present study was to survey the recommendations and
      practices regarding the first dental visit by young children, as reported by
      family physicians and pediatricians in the United States. METHODS: A
      representative sample of family physicians and pediatricians was surveyed in the
      year 2000. The initial survey was mailed out to 1,500 family physicians and 1,000
      pediatricians who were selected from the AMA Masterfile. After the first mailing,
      3 follow-up questionnaires and a postcard reminder were mailed to the
      nonresponders within a period of 3 months. The questionnaire described case
      scenarios of 2, 12-month-old children, one with low caries-risk and the other at
      high risk with noticeable cavitation of the maxillary front teeth. RESULTS: The
      response rate to the survey was 43% (622 out of 1,439) for family physicians and
      52% (493 out of 957) for pediatricians. When the case scenario of a child with
      high caries risk was presented, more than 90% of the respondents recommended that
      the child see a dentist as soon as possible. For the child with low caries-risk,
      the proportion of respondents recommending early dental visit was significantly
      lower: only about 19% of family physicians and 14% of pediatricians. For a child
      at low risk for dental caries, about 40% of family physicians and 63% of
      pediatricians recommended the first dental visit around the third birthday. The
      majority of the respondents (pediatricians=91% and family physicians=77%)
      reported frequent screening for gross tooth decay. However, only a minority of
      them (pediatricians=33% and family physicians=19%) frequently checked for early
      signs of tooth decay as part of their regular practice. CONCLUSIONS: US
      physicians can decide on referral patterns based on the risk status of a child.
      However, the majority of respondents do not regularly screen for early signs of
      early childhood caries.

PMID- 14649606
TI  - Early childhood caries and quality of life: child and parent perspectives.
AB  - PURPOSE: The purpose of this study was to investigate the effects of early
      childhood caries (ECC) on children's oral health-related quality of life (QOL)
      before and 4 weeks after its treatment, as assessed by the children themselves as
      well as by their parents/guardians. METHODS: This study had a longitudinal
      intervention design. Sixty-nine children diagnosed with ECC and 43 children
      without caries (combined children's mean age=50.4 months; range=22 to 70 months)
      and their parents/guardians responded to face-to-face administered surveys before
      a dental treatment was started (baseline assessment). Thirty-seven children with
      ECC completed dental rehabilitation. Four weeks after the treatment was
      completed, these 37 children as well as their parents/guardians responded to a
      second survey (follow-up assessment). RESULTS: The results show that children
      with ECC have significantly lower oral health-related QOL than children without
      ECC as assessed both by the children and the parents/guardians at baseline. The
      children with ECC who received dental treatment had a significantly improved oral
      health-related QOL at the follow-up assessment when compared with their baseline
      measurement as measured both with the children's self-ratings of oral health
      related QOL and the parents'/guardians' perception of their child's oral health
      related QOL. CONCLUSIONS: ECC and its treatment affect children's oral health
      related QOL in a significant way. Oral health-related QOL can be assessed validly
      and reliably both in self-reports from children as young as 36 months of age as
      well as by asking parents/guardians about their perceptions of their child's oral
      health-related QOL.

PMID- 14649608
TI  - Pacifier use in children: a review of recent literature.
AB  - Pediatric dentists are generally well aware of the oral implications of
      nonnutritive sucking (NNS). NNS via digit or pacifier can effect changes in the
      occlusion, including openbite, excessive overjet, and possibly posterior
      crossbite. Skeletal changes have also been attributed to NNS. There is some
      evidence that pacifiers may do less harm to the dentition, particularly because
      pacifier habits are often spontaneously shed at about 2 to 4 years of age. Digit
      habits are more likely to persist into the school-age years and can require
      appliance therapy for discontinuation. Thus, some authorities suggest that
      pacifiers be recommended for infants who engage in NNS. While pediatric dentists
      understand the oral and perioral effects of pacifiers, they may be less well
      versed in other aspects of pacifier use that have been reported in the medical,
      nursing, chemical, and psychological literature. This paper provides reviews of
      literature concerning the role of pacifier NNS in 4 areas: (1) sudden infant
      death syndrome; (2) breast-feeding; (3) otitis media and other infections; and
      (4) safety. Knowledge of current literature in these areas may assist pediatric
      dentists with their decisions of whether to recommend or discourage pacifier use
      in infants.

PMID- 14649607
TI  - Cytokine levels in gingival crevicular fluid of erupting primary teeth correlated
      with systemic disturbances accompanying teething.
AB  - PURPOSE: The aim of this study was to investigate whether there are increased
      levels of the inflammatory cytokines IL-1beta, IL-8, and TNFalpha in the gingival
      crevicular fluid (GCF) of erupting primary teeth. This increase could explain
      such clinical manifestations as fever, diarrhea, increased crying, and sleeping
      and eating disturbances that occur at this time. METHODS: Sixteen healthy
      children aged 5 to 14 months (mean=9.8 months) were examined twice a week over 5
      months. Gingival crevicular fluid samples were taken from erupting teeth. As a
      control, GCF was collected from the same teeth 1 month later. Cytokine production
      was measured by ELISA. Signs and clinical symptoms were listed. Pearson
      correlation coefficients were used in the comparisons described below. A paired t
      test was used to analyze the same variable at different times. RESULTS: Fifty
      teeth of the 16 children were studied. GCF samples were collected from 21 of
      these teeth. Statistically significant differences (P<.05) were found with regard
      to the occurrence of fever, behavioral problems, and coughing during the teething
      period and the control period. During the control period, 72% of the children did
      not exhibit any clinical manifestations, whereas during the teething period only
      22% of the children did not exhibit any clinical manifestations. The study
      revealed high levels of inflammatory cytokines during the teething period, with a
      statistically significant difference in TNFalpha levels (P<.05) between the
      teething period and the control period. Correlations were found between cytokine
      levels and some of the clinical symptoms of teething: IL-1beta and TNFalpha were
      correlated with fever and sleep disturbances; IL-beta and IL-8 were correlated
      with gastrointestinal disturbances; IL-1beta was correlated with appetite
      disturbances. CONCLUSIONS: Cytonkines appear in the GCF of erupting prmary teeth.
      The cytokine levels are correlated to some symptoms of teething.

PMID- 14649609
TI  - Adolescent pregnancy: a review of dental treatment guidelines.
AB  - More than 6% of adolescent females become pregnant in the United States per year,
      yet there is no concise guide for their dental treatment. The principles for
      medical management of these patients are not unlike those used for adult females,
      but the higher incidence of complications coupled with social and consent issues
      make their overall management more complex. Whether treating a pregnant
      adolescent or an adult, the primary goal is to maintain a safe environment for
      both the fetus and mother. Untreated dental disease can compromise the health of
      the mother and unborn child; therefore, dental treatment should not be withheld.
      In complicated pregnancies, dental practitioners should contact the patient's
      obstetrician prior to providing treatment or prescribing medication. With proper
      technique, dental radiographs do not place the fetus at risk and should be taken
      if they are of potential benefit. Preventive care should be delivered throughout
      pregnancy, and elective routine care is best delivered during the second
      trimester.

PMID- 14649610
TI  - Comparison of the efficacy of oral midazolam alone versus midazolam and
      meperidine in the pediatric dental patient.
AB  - PURPOSE: The purpose of this study was to compare midazolam alone (Group A: 1
      mg/kg) vs midazolam plus meperidine (Group B: 0.5 and 1 mg/kg, respectively) in
      regard to physiology and behavior of young children sedated for dental
      restorative care. METHODS: Twenty healthy children who met selection criteria
      were randomly assigned to 1 of 2 groups and subsequently treated in a
      prospective, crossover design. All sedative agents were administered orally, and
      all sedations included 50% nitrous oxide administered via a nasal hood. Heart
      rate, systolic and diastolic blood pressure, and behavior were recorded at 8
      procedural or time periods during the visits. Chi-square and ANOVA were used to
      analyze the data. RESULTS: No difference in physiology or behavior was found
      between groups. However, higher heart rates and disruptive behaviors occurred
      more frequently during or after local anesthesia administration. CONCLUSIONS:
      Oral midazolam alone is just as effective as midazolam with meperidine.
      Disruptive behaviors accounted for increased heart rates.

PMID- 14649611
TI  - Factors affecting outcomes of traumatically extruded permanent teeth in children.
AB  - PURPOSE: The objectives of the present study were to determine the prevalence of
      residual extrusion, pulpal necrosis, and resorption for extruded permanent teeth
      and to establish the effect of presentation and treatment factors. METHODS:
      Seventy-two traumatically extruded permanent incisors were studied at the
      Departments of Paediatric Dentistry in Belfast, Newcastle upon Tyne, and Glasgow.
      The mean age of the patients was 10.1 years (range=6 to 18 years). Clinical and
      radiographic outcomes were analyzed and related to presenting and treatment
      factors. RESULTS: The initial degree of extrusion was moderate for 46 teeth
      (64%), and the median delay prior to repositioning was 3 hours (range=1 to 168
      hours). Pulp necrosis occurred in 31 teeth (43%), residual extrusion was present
      in 16 teeth (23%), and inflammatory resorption occurred in 11 teeth (15%).
      Residual extrusion was significantly associated with a delay in repositioning the
      tooth, pulpal necrosis was significantly more common in teeth with closed apices
      and in severely extruded teeth, and inflammatory resorption was more common after
      pulpal necrosis. CONCLUSIONS: Residual extrusion could be minimized by earlier
      presentation and repositioning. The risk of pulpal necrosis is greatest for
      severely extruded teeth and for those with closed apices.

PMID- 14649612
TI  - Association of dental health parameters with oral lesion prevalence in human
      immunodeficency virus-infected Romanian children.
AB  - PURPOSE: This study assessed the association of caries, plaque accumulation,
      gingival health, and antiretroviral therapy (AT) with oral lesion prevalence in
      human immunodeficiency virus (HIV)-infected Romanian children. METHODS: A
      convenience sample of HIV-infected children who received dental care in 2
      hospitals were evaluated for oral lesions, caries (dfs+DFS/total teeth present),
      plaque (PI, Silness and Loe), and gingival indices (GI, Loe and Silness). Oral
      lesions were grouped as: (1) extraoral herpetic infections; (2) parotid gland
      swelling; (3) oral ulcerative lesions; and (4) fungal infections. A standardized
      operator performed the examinations and photographed the oral lesions for
      confirmation. Age, gender, and use of AT were documented. Data were analyzed by
      logistic and multiple regression, Pearson correlation and t test (P<.05).
      RESULTS: One hundred four children (mean age=11.7 years) were evaluated. Fungal
      infections were associated with increased caries rate (P=.002; OR=2.5) and
      increased GI (P=.01; OR=7.6). Caries, PI, and GI were associated with an increase
      in oral lesions (r=-0.472, P<.001). AT use was associated with decreased caries
      (P=.001, t test), but was not associated with decreased oral lesion prevalence.
      CONCLUSIONS: Oral lesions, especially candidiasis, are more common in HIV
      infected children with higher caries experience, gingival inflammation, and
      plaque accumulation. In children with limited access to medical care, the role of
      oral health appears to be important for decreasing the risk of common
      opportunistic infections.

PMID- 14649613
TI  - Quantitative assessment of enamel hypomineralization by KaVo DIAGNOdent at
      different sites on first permanent molars of children in China.
AB  - PURPOSE: The purpose of this study was to identify the most caries-susceptible
      site of pits and fissures on first permanent molars by quantitative evaluation of
      the mineralization in both caries-active and caries-free children, and to provide
      helpful information for cost-effective, targeted prevention. METHODS: Eighty-four
      caries-free and 85 caries-active children were selected from 800 6- to 7-year-old
      children with fully erupted first permanent molars. Hypomineralization of the
      central fossa (CF) and lingual pit (LP) of the maxillary or buccal pit (BP) of
      mandibular first permanent molars were evaluated by KaVo DIAGNOdent. Statistical
      analysis included grouped t test and single-factor variance analysis and paired
      comparison. RESULTS: CF of mandibular first permanent molars had significantly
      greater hypomineralization than other sites. The hypomineralization of the
      maxillary CF is more severe than that of LP. The extent of the hypomineralization
      of each site at the first permanent molar in caries-active children was
      significantly higher than that in caries-free children. CONCLUSIONS: Central
      fossae of first mandibular molars are the most hypomineralized sites in both
      caries-free and caries-active groups. The results suggest that preventive
      interventions should be targeted at the CF of mandibular molars with special
      concern given to the caries-active population.

PMID- 14649614
TI  - Primary tooth enamel surface topography with in vitro argon laser irradiation
      alone and combined fluoride and argon laser treatment: scanning electon
      microscopic study.
AB  - PURPOSE: The purpose of this descriptive scanning electron microscopic study was
      to characterize surface alterations in primary tooth enamel after in vitro argon
      laser irradiation alone and combined with topical fluoride treatment either
      before or after argon laser irradiation. METHODS: Twenty extracted or exfoliated
      primary teeth underwent soft tissue debridement and a fluoride-free prophylaxis.
      Buccal and lingual surfaces were determined to be caries-free by macroscopic
      examination (stereo-zoom binocular microscope, x16). Treatment groups were: (1)
      no-treatment control; (2) argon laser irradiation (ALI; 11.5 J/cm2); (3) 1.23%
      acidulated phosphate fluoride (APF before ALI); and (4) ALI before APF. Both
      buccal and lingual surfaces were evaluated following standard scanning electron
      microscopic preparation techniques. RESULTS: With controls, enamel surfaces were
      relatively smooth with occasional enamel prism ends present on their surfaces.
      There were no areas with cavitations or surface defects. With ALI, the lased
      surfaces were roughened mildly to moderately irregular without cavitation of the
      enamel or exposure of enamel prism ends. The surfaces possessed adherent granules
      to globules, with most being <3 microm in greatest dimension. Only occasional
      fine cracks and porosities in the surface coatings were noted and these were
      typically less than 1 microm in width or diameter. With APF before ALI, the
      surfaces possessed an irregular contour, with numerous granules to globules
      varying in size from 1 to 3 microm in greatest dimension. With ALI before APF, a
      homogenous confluent surface was present that masked typical enamel surface
      markings. The previously noted adherent granules and globules with argon laser
      treatment alone or APF before ALI were not seen. The argon laser effects on the
      enamel surfaces were masked by the uniformity of these surface coatings.
      CONCLUSIONS: Argon laser irradiation and combined APF and argon laser treatment
      of primary tooth enamel created surfaces that may provide a protective barrier
      against a cariogenic attack. The surface coatings associated with combined APF
      and argon laser treatment may contain fluoride-rich calcium and phosphate mineral
      phases that could act as reservoirs for fluoride, calcium, and phosphate and
      provide a certain degree of protection from a caries lesion challenge.

PMID- 14649615
TI  - An in vitro study of enamel surface microhardness following argon laser
      irradiation and acidulated phosphate fluoride treatment.
AB  - PURPOSE: The purpose of this in vitro study was to evaluate the effect of low
      fluence argon laser (AL) irradiation and acidulated phosphate fluoride (APF) gel
      treatment on enamel microhardness. METHODS: Twelve mandibular permanent molars
      were selected for this study. The teeth were sectioned generating 4 flat enamel
      surfaces per tooth. The flattened enamel tooth surfaces were randomly assigned to
      1 of 4 treatment groups: (1) no treatment (control); (2) the enamel surface was
      exposed to a 4-minute, 1.23% APF gel treatment; (3) the enamel surface was
      exposed to AL irradiation of 11.5 J/cm2 (0.23 1-W, 5-mm beam size, 10 seconds);
      and (4) the enamel surface was exposed to the same AL irradiation followed by an
      APF gel treatment. Using a Buehler Micromet II Digital Microhardness Tester,
      Knoop hardness was determined using a 1,000-gram load and a dwell time of 12
      seconds. Five hardness values were recorded for each enamel surface. Data were
      analyzed using ANOVA and Fisher's least significant difference post-hoc test.
      RESULTS: Mean surface hardness values (+/-SD) were 298+/-37 Knoop hardness (HK)
      for the no treatment (control), 270+/-70 HK for the APF-only group, 316+/-5 HK
      for the AL-only group, and 317+/-25 HK for the AL-before-APF group. The AL-only
      and AL-before-APF groups had significantly higher (P<.05) surface hardness values
      vs the APF-only group. CONCLUSIONS: Enamel surface microhardness is higher when
      exposed to low AL irradiation only or AL before APF vs a no treatment (control)
      enamel surface.

PMID- 14649616
TI  - Novel dental anomalies associated with congenital contractural arachnodactyly: a
      case report.
AB  - Congenital contractural arachnodactyly (CCA) is an inherited disorder of
      connective tissue similar to Marfan's syndrome. The craniofacial and oral
      features of a young girl with CCA are described. The patient has the typical
      features of CCA as well as some additional dental anomalies which have not
      previously been reported with this syndrome. These include banded pitted enamel
      hypoplasia and hypomineralization, long, spindly tapered roots, and pulp canal
      obliteration with multiple pulp stones. Dentists must be aware of the clinical
      features of a patient's syndrome to determine whether there are implications for
      dental treatment such as a need for antibiotic prophylaxis. It is important to
      exclude Marfan's syndrome as a differential diagnosis for CCA because the former
      has more associated complications and a less favorable prognosis.

PMID- 14649618
TI  - HAART, hepatitis C, activated T cells, and mortality.

PMID- 14649617
TI  - Microleakage and penetration ability of resin sealant versus bonding system when
      applied following contamination.
AB  - PURPOSE: The purpose of this study was to evaluate the microleakage and
      penetration ability of sealing materials applied under different conditions of
      contamination. METHODS: One hundred twenty extracted human molar teeth were
      randomly assigned to 12 groups. The treatment groups were defined by the
      combination of sealing materials (Concise; Optibond system; Optibond system plus
      Concise) and 4 surface conditions (no moisture and no saliva contamination;
      moisture contamination; dried saliva contamination; wet saliva contamination).
      Each tooth was subjected to thermal cycling (5,000 cycles at 5 degrees C-55
      degrees C) with a dwell time of 30 seconds and dye immersion (5% methylene blue
      for 24 hours). Microleakage, penetration ability, and fissure types were examined
      after sectioning. Multiple regression analyses and the Tukey test were used for
      statistical analysis. RESULTS: Concise showed significantly less microleakage
      than the Optibond system (P<.031) when the procedures were performed under no
      contamination or moisture contamination. However, when Concise was applied on the
      wet saliva-contaminated surfaces, considerably higher microleakage and unfilled
      areas were found compared to the use of Optibond alone or Optibond with Concise
      (P<.001). CONCLUSIONS: When there is saliva contamination, the use of Optibond
      alone or with Concise is beneficial for decreasing microleakage and increasing
      the penetration ability of sealants.

PMID- 14649619
TI  - Uncircumcised men have high HIV risk.

PMID- 14649620
TI  - A new meaning for "healthy worker effect".

PMID- 14649621
TI  - Rapid HIV testing and quality assurance.

PMID- 14649622
TI  - Abacavir plus lamivudine: a thymidine analogue-sparing NRTI backbone.

PMID- 14649623
TI  - Host factors may be more important than choice of antiretrovirals in the
      development of lipoatrophy.
AB  - Peripheral fat loss, or lipoatrophy, has been reported as an emerging
      complication of long-term antiretroviral regimens, mainly when nucleoside
      analogues are included. However, lipoatrophy does not develop in the majority of
      nucleoside inhibitor-treated patients, leading to the investigation of factors
      other than drug effects alone as potential contributors to this complication. We
      conducted a retrospective cohort study study and analysis of repository plasma
      samples taken from HIV-infected patients being treated with their initial
      antiretroviral regimen. CD4 cell count and plasma tumor necrosis factor (TNF),
      soluble TNF receptors, and leptin levels were assessed and correlated with the
      development of lipoatrophy. The most significant treatment-related factor in this
      study of patients on their first drug regimen was duration of antiretroviral
      therapy, rather than type of nucleoside inhibitor treatment. No association was
      found between lipoatrophy and specific nucleoside inhibitors, including
      zidovudine and stavudine. A significant association between lipoatrophy was found
      for 2 nondrug risk factors: older age and lower pretherapy body mass index. Our
      results emphasize the need for keeping in mind the role of host factors in the
      generation of lipoatrophy.

PMID- 14649624
TI  - Editorial comment: tackling the causes of lipoatrophy--not for the fainthearted.

PMID- 14649625
TI  - Metastatic carcinoma: an unusual cause of focal brain lesions in HIV infection.
AB  - The most common causes of focal brain lesions (FBLs) in patients with HIV
      infection are cerebral toxoplasmosis, primary central nervous system lymphoma
      (PCNSL), and progressive multifocal leukoencephalopathy. Neoplasms other than
      PCNSL are uncommon. We report a rare case of metastatic carcinoma causing an FBL
      in a patient with HIV infection. The diagnostic workup and further management of
      FBLs in HIV are outlined in this review. The standard approach includes a lumbar
      puncture and cerebrospinal fluid (CSF) analysis for cytology and Epstein-Barr
      virus (EBV) DNA testing by polymerase chain reaction. Empiric therapy for PCNSL
      is justifiable for patients with positive CSF EBV-DNA test results and a positive
      single-photon emission computed tomography (SPECT) scan, especially if there has
      been no response to antitoxoplasmosis therapy. Brain biopsy may be indicated,
      however, in select cases that do not meet these criteria in order to identify
      potentially treatable infections and PCNSL.

PMID- 14649626
TI  - Editorial comment: diagnosis of focal brain lesions--old lessons retaught.

PMID- 14649627
TI  - Survival of endospores of Bacillus subtilis on spacecraft surfaces under
      simulated martian environments:   implications for the forward contamination of
      Mars.
AB  - Experiments were conducted in a Mars simulation chamber (MSC) to characterize the
      survival of endospores of Bacillus subtilis under high UV irradiation and
      simulated martian conditions. The MSC was used to create Mars surface
      environments in which pressure (8.5 mb), temperature (-80, -40, -10, or +23
      degrees C), gas composition (Earth-normal N2/O2 mix, pure N2, pure CO2, or a Mars
      gas mix), and UV-VIS-NIR fluence rates (200-1200 nm) were maintained within tight
      limits. The Mars gas mix was composed of CO2 (95.3%), N2 (2.7%), Ar (1.7%), O2
      (0.2%), and water vapor (0.03%). Experiments were conducted to measure the
      effects of pressure, gas composition, and temperature alone or in combination
      with Mars-normal UV-VIS-NIR light environments. Endospores of B. subtilis, were
      deposited on aluminum coupons as monolayers in which the average density applied
      to coupons was 2.47 x 10(6) bacteria per sample. Populations of B. subtilis
      placed on aluminum coupons and subjected to an Earth-normal temperature (23
      degrees C), pressure (1013 mb), and gas mix (normal N2/O2 ratio) but illuminated
      with a Mars-normal UV-VIS-NIR spectrum were reduced by over 99.9% after 30 sec
      exposure to Mars-normal UV fluence rates. However, it required at least 15 min of
      Mars-normal UV exposure to reduce bacterial populations on aluminum coupons to
      non-recoverable levels. These results were duplicated when bacteria were exposed
      to Mars-normal environments of temperature (-10 degrees C), pressure (8.5 mb),
      gas composition (pure CO2), and UV fluence rates. In other experiments, results
      indicated that the gas composition of the atmosphere and the temperature of the
      bacterial monolayers at the time of Mars UV exposure had no effects on the
      survival of bacterial endospores. But Mars-normal pressures (8.5 mb) were found
      to reduce survival by approximately 20-35% compared to Earth-normal pressures
      (1013 mb). The primary implications of these results are (a) that greater than
      99.9% of bacterial populations on sun-exposed surfaces of spacecraft are likely
      to be inactivated within a few tens of seconds to a few minutes on the surface of
      Mars, and (b) that within a single Mars day under clear-sky conditions bacterial
      populations on sun-exposed surfaces of spacecraft will be sterilized.
      Furthermore, these results suggest that the high UV fluence rates on the martian
      surface can be an important resource in minimizing the forward contamination of
      Mars.

PMID- 14649628
TI  - Space Biology Group: basic research, biotechnology, tissue engineering, and
      instrument development.
AB  - At the beginning of space flight, the investigations were oriented essentially
      toward the health of the astronauts. But in the last three decades space biology
      has evolved from "try-and-see" experiments to sophisticated basic and applied
      research with well-based hypotheses as well as studies on the use of low gravity
      in biological applications. In 1977 the Space Biology Group of the Swiss Federal
      Institute of Technology, Zurich, began its activities in space research. A
      summary of the experiments performed to date, from basic research on the human
      immune system to the development of sophisticated instruments for biotechnology
      and medical application, is presented here.

PMID- 14649630
TI  - Focus on psychiatry in France.

PMID- 14649629
TI  - Effects of Command and Control Vehicle (C2V) operational environment on soldier
      health and performance.
AB  - The purpose of this project was to use NASA technology to assist the US Army in
      the assessment of motion sickness incidences and effects on soldier performance
      and mood states within the Command and Control Vehicle (C2V). Specific objectives
      were (1) to determine if there was a significant difference between three
      internal configurations of the C2V and/or between seats within these vehicles;
      (2) to determine if there was a significant difference between the park, move, or
      short-halt field conditions; and (3) to validate a method of converging
      indicators developed by NASA to assess environmental impact of long duration
      spaceflight on crewmembers, using a large sample of subjects under ground-based
      operational conditions.

PMID- 14649631
TI  - 10 most commonly asked questions about thoracic outlet syndrome.

PMID- 14649632
TI  - 10 most commonly asked questions about Huntington's disease.

PMID- 14649633
TI  - Applying verbal autopsy to determine cause of death in rural Vietnam.
AB  - AIMS: Verbal autopsy (VA) is an attractive method for ascertaining causes of
      death in settings where the proportion of people who die under medical care is
      low. VA has been widely used to determine causes of childhood and maternal
      deaths, but has had limited use in assessing causes in adults and across all age
      groups. The objective was to test the feasibility of using VA to determine causes
      of death for all ages in Bavi District, Vietnam, in 1999, leading to an initial
      analysis of the mortality pattern in this area. METHODS: Trained lay field
      workers interviewed a close caretaker of the deceased using a combination
      closed/open-ended questionnaire. RESULTS: A total of 189 deaths were studied.
      Diagnoses were made by two physicians separately, with good agreement (kappa =
      0.84) and then combined to reach one single underlying cause of death for each
      case. The leading causes of death were cardiovascular and infectious diseases
      (accounting for 20.6% and 17.9% of the total respectively). Drowning was very
      prevalent in children under 15 (seven out of nine cases of drowning were in this
      age group). DISCUSSION: One month seemed an acceptable minimum recall period to
      ensure mourning procedures were over. A combination VA questionnaire was an
      appropriate instrument provided it was supported by adequate training of
      interviewers. Two physicians were appropriate for making the diagnoses but
      predefined diagnostic methods for common causes should be developed to ensure
      more replicable results and comparisons, as well as to observe trends of
      mortality over time. The causes of death in this study area reflect a typical
      pattern for developing countries that are in epidemiological transition. No
      maternal deaths and a low infant mortality rate may be the result of improvements
      in maternal and child health in this study area. Using the VA gave more precise
      causes of death than those reported at death registration. Although the validity
      of the VA method used has not been fully assessed, it appeared to be an
      appropriate method for ascertaining causes of death in the study area.

PMID- 14649634
TI  - Mortality from cardiovascular diseases in Bavi District, Vietnam.
AB  - AIMS: Like other developing countries, Vietnam is undergoing epidemiological
      transition, which is characterized by many changes in terms of morbidity and
      mortality patterns. The fact that cardiovascular diseases (CVD) are leading
      causes of death in hospitals in the whole country was ascertained from annual
      statistics. However, the magnitude of the burden of mortality from CVD at the
      community level remained unknown. The aims of the study were to outline CVD
      mortality during health transition in a rural community in the north of Vietnam
      and to examine associations between CVD mortality and the socioeconomic status of
      the population. METHODS: Within an established demographic surveillance system
      (DSS), verbal autopsy (VA) was used to identify the burden of mortality from CVD.
      Cohort analysis was used in this study to measure associations between CVD
      mortality and socioeconomic determinants. RESULTS: CVD emerged as a leading cause
      of death in the study area, accounting for more than infectious and parasitic
      diseases combined. CVD killed many people among the most economically productive
      age group, both men and women, in all socioeconomic groups. Occupational status
      was shown to be significantly associated with CVD mortality. DISCUSSION: Already
      at this point in the epidemiological transition, there is evidence of a
      substantial burden of CVD in rural Vietnam. Although this study was not able to
      show trends, the current situation is a cause for concern in health policy and
      planning. Verbal autopsy methods and CVD risk factor evaluations will form
      important parts of future research agendas.

PMID- 14649635
TI  - Effects of ethanol on glucagon-stimulated protein phosphorylation in isolated
      hepatocytes.
AB  - Ethanol has profound acute effects on hepatic metabolism. While many of these
      effects are mediated via the redox imbalance that accompanies hepatic ethanol
      oxidation via the alcohol dehydrogenase (ADH) pathway, there is increasing
      evidence that ethanol also perturbs hepatic metabolism via its modulation of
      cyclic AMP-mediated signalling pathways. This paper examines the effects of
      ethanol on glucagon-stimulated protein phosphorylation using SDS-PAGE to analyse
      the 32P-labelling of cytosolic peptides in isolated rat hepatocytes pre
      equilibrated with 32PO4(3-). We show that ethanol has biphasic effects on
      glucagon-stimulated protein phosphorylation. At a low concentration (50 mM),
      ethanol decreased the phosphorylation of certain peptides, whereas at higher
      concentrations (100-200 mM) it increased the 32P-labelling of all of the eleven
      glucagon-stimulated cytosolic peptides. The non-metabolizable alcohol 2
      methylpyrazole-2-ol had no effects on glucagon-stimulated protein
      phosphorylation. The ADH inhibitor 4-methylpyrazole at 150 mM ethanol
      concentration abolished the potentiating effect of ethanol on the glucagon
      stimulated phosphorylation of most peptides. In conclusion, the results indicate
      that ethanol alters glucagon-receptor-dependent protein phosphorylation in
      isolated hepatocytes via a complex mechanism that is partially dependent on
      ethanol oxidation via ADH.

PMID- 14649636
TI  - A probabilistic approach to interpreting verbal autopsies: methodology and
      preliminary validation in Vietnam.
AB  - AIMS: Verbal autopsy (VA) has become an important tool in the past 20 years for
      determining cause of death in communities where there is no routine registration.
      In many cases, expert physicians have been used to interpret the VA findings and
      so assign individual causes of death. However, this is time consuming and not
      always repeatable. Other approaches such as algorithms and neural networks have
      been developed in some settings. This paper aims to develop a method that is
      simple, reliable and consistent, which could represent an advance in VA
      interpretation. METHODS: This paper describes the development of a Bayesian
      probability model for VA interpretation as an attempt to find a better approach.
      This methodology and a preliminary implementation are described, with an
      evaluation based on VA material from rural Vietnam. RESULTS: The new model was
      tested against a series of 189 VA interviews from a rural community in Vietnam.
      Using this very basic model, over 70% of individual causes of death corresponded
      with those determined by two physicians increasing to over 80% if those cases
      ascribed to old age or as being indeterminate by the physicians were excluded.
      DISCUSSION: Although there is a clear need to improve the preliminary model and
      to test more extensively with larger and more varied datasets, these preliminary
      results suggest that there may be good potential in this probabilistic approach.

PMID- 14649637
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy--42nd meeting.
      27-30 September 2002, San Diego, CA, USA.

PMID- 14649639
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy--42nd meeting.
      Advances in antivirals. 27-30 September 2002, San Diego, CA, USA.

PMID- 14649638
TI  - The economic burden of unintentional injuries: a community-based cost analysis in
      Bavi, Vietnam.
AB  - AIMS: Relatively little is known about patterns of injury at the community level
      in Vietnam and their economic consequences. This study sought to estimate the
      costs of various unintentional injuries in Bavi District during one year; to
      describe how costs depended on gender, age, circumstances, and severity of
      injury; and to describe how the economic burden of unintentional injuries was
      distributed between households, government, and health insurance agency. METHODS:
      A cohort study was undertaken, which involved four cross-sectional household
      surveys among sampled communities in the Bavi District during the year 2000, each
      asking about injuries in the preceding three months. The costing system in public
      healthcare in Vietnam was applied as well as information from the victims.
      RESULTS: The total cost of injuries over one year in Bavi District was estimated
      to be D3,412,539,000 (Vietnamese dong) (US$235,347), equivalent to the annual
      income of 1,800 people. In total, 90% of this economic burden fell on households,
      only 8% on government, and 2% on the health insurance agency. The cost of a
      severe injury to the corresponded to approximately seven months of earned income.
      Home and traffic injuries together accounted for more than 80% of the total cost,
      45% and 38% respectively. The highest unit cost was related to traffic injuries,
      followed by home, "other", work-related, and school injuries in descending order.
      DISCUSSION: The results can be considered as an economic baseline that can be
      used in evaluations of future interventions aimed at preventing injuries.

PMID- 14649640
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy--42nd meeting.
      Oxazolidinones and other antibacterials. 27-30 September 2002, San Diego, CA,
      USA.

PMID- 14649641
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy--42nd meeting.
      Investigational drugs. 27-30 September 2002, San Diego, CA, USA.

PMID- 14649642
TI  - Self-reported illness and use of health services in a rural district of Vietnam:
      findings from an epidemiological field laboratory.
AB  - AIMS: The aims of the study were to assess the pattern of self-reported illness
      as well as use of health services in a rural district in Vietnam, and to analyse
      these in relation to gender, age, education level, occupation, and economic
      status. METHODS: A population-based survey of 11,089 households was conducted in
      1999. Through household interviews, data were collected on self-reported health,
      use of health services during the four weeks prior to the interview, and other
      background factors. RESULTS: The prevalence of self-reported illness was 48%.
      Cough, fever, and headache were the most commonly reported symptoms (20%) while
      cardiovascular disorders were least reported (0.6%). Occurrence of illness was
      significantly lower in groups with higher education, especially among men, but
      there was no difference between occupational and economic groups. Self-treatment
      was very common (69%). Private health facilities were used to a large extent,
      while community health stations played a less important role. Use of district
      hospitals was significantly higher among employed people. DISCUSSION: An
      epidemiological field laboratory enabled analysis of self-reported illness and
      use of health services, which is important for planning of health services. We
      found a high level of reported illness but a very low utilization of community
      health services. Better knowledge about illness patterns could be important for
      improving quality of and access to community health services.

PMID- 14649643
TI  - BioPartnering Europe--tenth annual conference. 13-15 October 2002, London, UK.

PMID- 14649644
TI  - BioPartnering Europe--tenth annual conference. Investing in global partnerships
      I. 13-15 October 2002, London, UK.

PMID- 14649645
TI  - Knowledge of tuberculosis and associated health-seeking behaviour among rural
      Vietnamese adults with a cough for at least three weeks.
AB  - AIMS: Good general lay knowledge of tuberculosis (TB), its cause and treatment is
      considered important for both prompt healthcare seeking and adherence to
      treatment. The main aim of this study was to describe the knowledge of TB among
      med and women with a cough for more than three weeks and to see how their health
      seeking related to TB knowledge. METHODS: A population-based survey was carried
      out within a demographic surveillance site in Vietnam. The study population
      included 35,832 adults aged 15 years or over. Cough cases were identified at
      household level and structures interviews were carried out with all cases of
      cough in person. RESULTS: A total of 559 people (1.6%) reported coughing with a
      duration of three weeks or longer (259 men and 300 women). A large proportion of
      individuals with a cough for more than three weeks had limited knowledge of the
      causes, transmission modes, symptoms, and curability of TB. Men had a
      significantly higher knowledge score than women (3.04 vs 2.55). Better knowledge
      was significantly related to seeking healthcare and seeking hospital care. More
      men than women did not take any health care action at all. DISCUSSION: Health
      education for TB thus seems to be useful, but efforts must be made to ensure that
      both men and women in different socioeconomic contexts can access the
      information.

PMID- 14649646
TI  - BioPartnering Europe--tenth annual conference. Investing in global partnerships
      II. 13-15 October 2002, London, UK.

PMID- 14649647
TI  - Inflammation Research Association--11th national conference. 6-10 October 2002,
      Bolton Landing, NY, USA.

PMID- 14649648
TI  - Inflammation Research Association--11th national conference. Novel therapeutic
      uses of p38 inhibitors.6-10 October 2002, Bolton Landing, NY, USA.

PMID- 14649650
TI  - European College of Neuropsychopharmacology--15th international congress. 5-9
      October 2002, Barcelona, Spain.

PMID- 14649649
TI  - Faces of poverty: sensitivity and specificity of economic classifications in
      rural Vietnam.
AB  - AIMS: Poverty concepts and measurements have occupied philosophers for centuries
      and are subject to debate by researchers. A wide range of possible measures have
      been developed and used. Most research is country specific and different methods
      produce different pictures of poverty. This study aimed to compare measures of
      poverty within an epidemiological field laboratory in Bavi District, northern
      Vietnam (FilaBavi) and specifically to find out whether the official economic
      classification made by the local authority matched other measurements of
      socioeconomic status. METHODS: Structured questionnaires were used to collect
      socioeconomic information in 11,547 households. In addition, the official
      classification for individual households was recorded. Five economic indicators
      were constructed: income, expenditure, household assets, housing conditions, and
      local authority's estimation. RESULTS: Official economic classification and
      housing score were symmetrically distributed, while assets score and particularly
      income were highly skewed. Design effects were high because of high intra-cluster
      correlations. No indicator was closely correlated with any other. Sensitivity and
      positive predictive value for poverty were generally low for all indicators.
      DISCUSSION: The authors' findings do not suggest that any of the indicators used
      is substantially better than the other or better than the Official Economic
      Classification made by local authority. The results also show that no indicator
      is particularly useful to predict the values of any other indicator and different
      poverty indicators may classify different socioeconomic groups as poor.

PMID- 14649651
TI  - American Neurological Association 127th meeting. 13-16 October 2002, New York,
      NY, USA.

PMID- 14649653
TI  - Monoclonal Antibodies in Cancer--Second International Congress. 29 August-1
      September 2002, Banff, Canada.

PMID- 14649652
TI  - Signal Transduction Therapeutics--SMi conference. 2-3 October 2002, The Hatton,
      London, UK.

PMID- 14649654
TI  - Medicare and Medicaid programs; religious nonmedical health care institutions and
      advance directives. Final rule.
AB  - This final rule implements requirements under the Balanced Budget Act of 1997,
      which set forth requirements for the new Religious Nonmedical Health Care
      Institution program and advance directives. This rule finalizes the Medicare
      requirements for coverage and payment of services furnished by religious
      nonmedical health care institutions, the conditions of participation that these
      institutions must meet before they can participate in Medicare, and the
      methodology we will use to pay these institutions and monitor expenditures for
      services they furnish. This rule also finalizes the rules governing States'
      optional coverage of religious nonmedical health care institution services under
      the Medicaid program. Additionally, this final rule addresses comments we
      received on the November 30, 1999, interim final rule and also makes minor
      changes to clarify our policy. Lastly, this rule incorporates a minor change to
      the requirements for advance directives.

PMID- 14649655
TI  - Medicare program; reduction in Medicare Part B premiums as additional benefits
      under Medicare+Choice plans. Final rule.
AB  - This final rule revises the regulations to provide for a Medicare+Choice
      organization to offer a reduction in the standard Medicare Part B premium as an
      additional benefit under one or more Medicare+Choice (M+C) plans. The legislation
      specifies that the reduction to the Medicare Part B premium cannot exceed the
      standard Medicare Part B premium amount and cannot be applied to surcharges.
      Surcharges are increased premiums for late enrollment and for reenrollment. The
      Medicare Part B premium may be collected by a variety of methods: Paid directly
      to the Centers of Medicare & Medicaid Services by the beneficiary; collected as
      an adjustment to any Social Security, Railroad Retirement, or Civil Service
      Retirement benefits; paid by an employer as part of an annuity package; or, paid
      by the State for individuals enrolled in a qualifying State Medicaid program.
      This legislation applies to benefits under Medicare M+C plans offered by an M+C
      organization electing this option, beginning January 1, 2003. This final rule
      revises the regulations to set out the basic rules under section 606 of the
      Medicare, Medicaid, and SCHIP Benefits Improvement Protection Act of 2000 (BIPA)
      for adjustment and payment of the Medicare Part B premium.

PMID- 14649657
TI  - [Current treatment of dermatophytosis].
AB  - The aim of this review is to discuss topical and systemic antifungal treatment of
      dermatophyte infections with current antifungal drugs.

PMID- 14649658
TI  - The palliative care needs of ethnic minority patients: staff perspectives.

PMID- 14649660
TI  - Partnerships with faith-based groups: running on more than faith.

PMID- 14649662
TI  - Intellectual impairment in children with blood lead concentrations below 10
      microg per deciliter.

PMID- 14649661
TI  - Mirrors at the birth of Aphrodite.

PMID- 14649663
TI  - Decline in invasive pneumococcal disease after the introduction of protein
      polysaccharide conjugate vaccine.

PMID- 14649664
TI  - Embolization of cannula fragments during insertion of central catheters.

PMID- 14649665
TI  - Quality of life and self-esteem in children treated for idiopathic short stature.

PMID- 14649666
TI  - Thalidomide therapy for juvenile-onset entero-Behcet disease.

PMID- 14649667
TI  - High rate of malignant transformation in atypical oral lichen planus lesions.

PMID- 14649668
TI  - Lack of association between early onset of breast cancer and numbers of affected
      relatives in an Iranian population.

PMID- 14649669
TI  - The information and support needs of women at high risk of familial breast and
      ovarian cancer: how can cancer genetic services give patients what they want?

PMID- 14649671
TI  - [Apoptosis and tumors].

PMID- 14649672
TI  - Understanding the risk factors for adverse birth outcomes in adolescent
      pregnancies.

PMID- 14649673
TI  - Differing risk factors for premature birth in adolescent mothers and adult
      mothers.
AB  - BACKGROUND: Although the survival rate of premature infants has improved, the
      prevalence of premature birth has not changed or has even increased. The purpose
      of this study is to analyze the demographic, psychosocial support, family
      planning, and health behavior risk factors for premature birth. METHODS: This
      county-based, cross-sectional study collected information on 1,146 first-time
      mothers, including 556 adolescents (< 20 years old) and 590 adults (20-34 years
      old). Univariate and multivariate logistic regression analyses were used to study
      risk factors associated with premature birth. RESULTS: The prevalence of
      premature birth was 11.4% for adolescent mothers and 8.4% for adult mothers.
      Younger adolescent mothers (< 18 years old) (14.5%), fewer than 10 prenatal
      visits (12.5% vs. 6.7%), hypertension (33.3% vs. 8.9%), weight gain less than 10
      kg (14.6% vs. 8.8%), drinking alcohol (23.1% vs. 9.5%), unintended pregnancy
      (13.6% vs. 7.4%), no parental support (16.8% vs. 9.1%), and victim of domestic
      violence (16.0% vs. 9.3%) were associated with a higher risk of premature birth
      (p < 0.05). In multivariate logistic regression analysis stratified by mother's
      age, prenatal visits less than 10 times (OR 2.68; 95% CI [1.38, 5.21]) and
      drinking alcohol (OR 25.0; 95% CI [1.35-460.49]) were significantly associated
      with premature birth for adult mothers but unintended pregnancy (OR 2.34; 95% CI
      [1.28, 4.27]) was the only significant factor for adolescent mothers.
      CONCLUSIONS: Differing risk factors for premature birth were found between
      adolescent and adult mothers. Effective family planning before gestation, alcohol
      abstinence, and regular prenatal visits for screening psychosocial, medical, and
      obstetric conditions during pregnancy are mandatory for the prevention of
      premature birth.

PMID- 14649674
TI  - Rapid detection of intron 22 inversions of the factor VIII gene in Chinese
      patients with severe hemophilia A.
AB  - BACKGROUND: Hemophilia A is caused by mutations in the gene for coagulation
      factor VIII. Recently, it has been reported that about half of the patients with
      severe hemophilia A have a large genomic inversion of the factor VIII gene. We
      tried to use a rapid method to detect this important mutation in the Chinese
      hemophiliacs. METHODS: Based on amplification of the leaky mRNA of factor VIII
      gene in peripheral blood lymphocytes, a reverse-transcription polymerase chain
      reaction (RT-PCR) method was applied to detect the inversion of intron 22 in the
      Chinese patients with severe hemophilia A. RESULTS: This mutation was detected in
      7 of 20 (35%) severe hemophilia A patients from unrelated families. The mutation
      was not found in 3 patients of non-severe hemophilia A and 4 normal controls.
      Family history of bleeding tendency could not be traced in 3 of the 7 patients
      with intron 22 inversion. CONCLUSIONS: Intron 22 inversion of the factor VIII
      gene is the major genetic mutation for severe hemophilia A in Taiwan. There is a
      high probability of de novo mutation for this genetic change. The results were
      consistent with the concept that intron 22 inversion will always result in severe
      deficiency of factor VIII. Rapid detection of this common mutation can helpfully
      guide the direction of molecular study in genetic counselling.

PMID- 14649675
TI  - Serum interleukin-6 level as a diagnostic test in children with sepsis.
AB  - BACKGROUND: This study was performed to determine the serum concentrations of
      interleukin-6 (IL-6) during the early course of bacterial infections disease in
      children, and to evaluate the usefulness of IL-6 as a diagnostic test alone and
      in combination with C-reactive protein (CRP). METHODS: We measured serum IL-6
      values in 3 groups of children on their first day of admission, from January 2001
      to December 2001: group 1, patients with clinical and microbiological evidence of
      sepsis (n = 13); group 2, patients with clinical and chest radiographical
      evidence of pneumonia (n = 18); and group 3, patients with no signs of infection
      (control group) (n = 16). Kruskal-Wallis tests were used to compare the
      difference of IL-6 values between groups and control subjects. RESULTS: IL-6
      values were significantly higher in groups 1 and 2 compared with those in the
      control group (p < 0.001). No significant differences were found between the
      groups 1 and 2. As a diagnostic test, IL-6 (> or = 20 pg/mL) alone yielded a
      sensitivity of 68%, a specificity of 88%, a positive predictive value of 71%, and
      a negative predictive value of 58%. A combined parameter of IL-6 (> or = 20
      pg/mL) and CRP (> or = 1 mg/dL) yielded a sensitivity of 94%, a specificity of
      63%, a positive predictive value of 79%, and a negative predictive value of 87%.
      CONCLUSION: IL-6 levels increase in children with sepsis. In combination with
      CRP, IL-6 seems to be a valuable parameter in the early diagnosis of pediatric
      infections.

PMID- 14649676
TI  - The long-term results of one time treatment by continuously fractionated
      transpupillary thermotherapy for occult choroid neovascularization membrane of
      age-related macular degeneration.
AB  - BACKGROUND: This study was to assess the long-term results of a novel
      continuously fractionated transpupillary thermotherapy (cfTTT) in treating occult
      choroid neovascularization membrane (CNV) of age-related macular degeneration
      (ARMD). METHODS: After informed consent was obtained, 19 patients were treated
      with cfTTT in 21 eyes. The diode laser (810 nm) was applied with 6 continuous 9
      second sessions to the neovascular membrane. Each session lasted 9 seconds. Every
      spot (1 mm on retina) was in close contact with each other to entirely cover the
      CNV. RESULTS: The average age was 75.9 years (from 61 to 86 years). The mean
      follow-up time was 19.6 months (from 15 to 24 months). Five eyes (23.8%) had
      improved visual acuity by 2 or more lines, 6 eyes (28.5%) by 1 line, and 10 eyes
      (47.6%) had no change in visual acuity. None had decreased vision. In final
      fluorescein angiography, all eyes treated revealed decreased fluorescein leakage.
      CONCLUSIONS: cfTTT shows no deleterious side effects in treating subfoveal or
      juxtafoveal CNV of ARMD at long-term follow-up and is at least as effective as
      long-pulse TTT.

PMID- 14649677
TI  - The combination of systemic antibiotics and antibiotics impregnated cement in
      primary total knee arthroplasty in patients of rheumatoid arthritis--evaluation
      of 60 knees.
AB  - BACKGROUND: We evaluated the effect of combination of systemic antibiotics and
      antibiotics-impregnated cement in prevention of deep infection in primary total
      knee arthroplasty (TKA) in patients of rheumatoid arthritis (RA). METHODS:
      Between 1993-2000, primary TKA were performed for 60 RA patients. Systemic
      antibiotics with cefazolin and gentamycin were applied in all the patients.
      Cefuroxime-impregnated cement was used for fixation of tibial and patellar
      components in all the patients; femoral component was fixed noncementedly in 45
      patients (hybrid TKA) and cementedly in 15 patients (cemented TKA). The
      preoperative, intraoperative and postoperative courses were evaluated in detail.
      The mean follow-up period was 61 months (range: 24-108 months). The effect of
      cefuroxime-impregnated cement in the prevention of postoperative deep infection
      in primary TKA in cases of RA was evaluated. RESULTS: Except 1 (1.6%) superficial
      infection, no other complication was noted. There was no deep infection, either.
      CONCLUSIONS: Cefuroxime-impregnated cement combining with systemic antibiotics
      seems to be effective in the prevention of early or intermediate deep infection
      in primary TKA in patients of RA.

PMID- 14649678
TI  - The symptoms of renal cell carcinoma related to patients' survival.
AB  - BACKGROUND: The aim of this study was to compare outcomes in patients presenting
      with incidental renal cell carcinoma (RCC), symptomatic RCC and paraneoplastic
      syndromes in RCC. METHODS: From October 1982 to June 2001, 312 patients with RCC
      were retrospectively enrolled. The patients were classified as: 1) incidental
      group: the patients without symptoms whose tumor was discovered incidentally; 2)
      symptomatic group: the patients presenting symptoms related to renal tumor; 3)
      paraneoplastic syndrome group: patients whose tumors were associated with
      paraneoplastic syndromes. Log rank testing was used to analyze statistical
      differences in the survival period among the three groups. RESULTS: The
      distribution of each group was 25.6% (n = 80) in group 1, 55.8% (n = 174) in
      group 2 and 18.6% (n = 58) in group 3. The mean tumor size was 5.0 cm in group 1,
      7.5 cm in group 2 and 8.3 cm in group 3 (p < 0.0001). The incidence of earlier
      stage (stages I and II) was 80% in group 1, 40.2% in group 2 and 15.5% in group 3
      (p < 0.0001). The 10-year survival rate for group 1 patients was 68.6%, for group
      2 patients was 45.6% and for group 3 patients was 12.3% (p < 0.0001).
      CONCLUSIONS: The incidental RCCs were smaller in size and at a lower tumor stage
      than symptomatic tumors. The paraneoplastic syndromes in patients with RCCs had a
      grave prognosis. The symptoms of a patient with RCC can be used as a prognostic
      factor related to survival.

PMID- 14649679
TI  - The extended lateral arm flap in head and neck reconstruction.
AB  - BACKGROUND: The lateral arm flap has been proven to be a reliable and versatile
      flap for the coverage of small to moderated-sized defects, especially in the head
      and neck and in the extremities. This flap has been modified by either extending
      the vascular pedicle or the flap territory. METHODS: From September 1997 to
      October 2000, we performed 17 free lateral arm flaps with extension of the flap
      size, including 1 osteofasciocutaneous flap for the coverage of head and neck
      defects. The reconstructions included a partial circumference defect of the
      esophagus, extensive intraoral defects, through-and-through bucco-cheek defect,
      etc. Follow-up was from three months to 12 months, with an average of 8 months.
      RESULTS: All but one flaps survived completely. Necrosis of the distal part
      occurred in one flap. Follow-up of donor sites revealed minimal morbidity when
      the flaps were extended to the below-elbow level. CONCLUSIONS: The cutaneous
      territory of the lateral arm flap, based on the posterior radial collateral
      artery, can be extended distally onto the forearm up to 10 cm. The center point
      of the flap design could be located more distally toward the lateral epicondyle
      in order to increase the size of the flap and the length of the vascular pedicle.
      The lateral arm flap provides a considerable amount of thin, pliable
      fasciocutaneous tissue. The advantages of the flap are constant anatomy, very
      easy and fast dissection, and the donor site being easier to camouflage than that
      of the radial forearm flap. The lateral arm flap is an excellent choice of
      fasciocutaneous flap for the reconstruction of head and neck defects.

PMID- 14649680
TI  - Glomus tumor of the trachea.
AB  - Glomus tumor of the trachea is extremely rare. There were approximately 15
      reported cases before. Herein, we report another case of glomus tumor of the
      trachea in a 50-year-old woman presenting with cough and dyspnea for 8 years. She
      suffered from hemoptysis for 1 day before this admission. Bronchoscopy and CT
      scan showed a polypoid tumor protruding into the tracheal lumen and with
      extraluminal extension. The tumor was located at 9 cm below the vocal cord and
      1.5 cm above the carina. It measured 2.5 x 2.5 x 2.0 cm and arose from the
      posterior wall of the trachea. Microscopically, the tumor consisted of a sheet of
      uniform cells surrounding the vascular spaces. Only few scattered tumor cells
      showed weak positive staining for muscle actin (HHF-35) by immunohistochemical
      stain. Ultrastructural study confirmed the presence of small amount of
      myofibrillar bundles with focal densities in some of the tumor cells. Other cells
      exhibited only rare or very sparse myofilaments. Characteristic feature of fine
      pinocytotic vesicles along the plasma membrance of the tumor cells was also
      noted.

PMID- 14649681
TI  - Endoscopic treatment in a patient with obstructive jaundice caused by pancreatic
      pseudocyst.
AB  - We report a case of chronic alcoholic pancreatitis with obstructive jaundice due
      to compression of the common bile duct by pancreatic pseudocyst. Ultrasonography
      and computed tomographic scan on admission demonstrated an 8 cm cystic lesion
      located at the head of the pancreas. Endoscopic retrograde
      cholangiopancreatography (ERCP) revealed a segment of narrowing at the distal
      common bile duct which was compressed by the pancreatic pseudocyst. Communication
      between the cyst and pancreatic duct was also noted. Bacteriological examination
      of cystic contents yielded the growth of Proteus vulgaris, Morganella morganii,
      Stenotrophomonas maltophilia and Pseudomonas aeruginosa. The patient was treated
      with broad-spectrum antibiotic, endoscopic sphincterotomy, endoscopic
      nasopancreatic duct drainage, and transpapillary pancreatic endoprosthesis.
      Jaundice subsided gradually during admission and a marked reduction of pancreatic
      pseudocyst was found 18 months after discharge.

PMID- 14649682
TI  - Right coronary artery arising from the left main stem with dynamic compression by
      great vessels.
AB  - Anomalous origin of the right coronary artery from the left main stem is a very
      rare congenital anomaly. The entrapment of its course between the aorta and
      pulmonary artery can cause dynamic blood flow limitation. We report a 68-year-old
      female presenting with recurrent chest pain and a positive treadmill exercise
      test. The coronary angiography disclosed anomalous origin of the right coronary
      artery from the left main stem with dynamic compression between aortic root and
      pulmonary trunk during the systolic phase. With hesitation about surgical
      revascularization, the patient was maintained on oral medication uneventfully.

PMID- 14649683
TI  - Functional nerve recovery after bridging a 15 mm gap in rat sciatic nerve with a
      biodegradable nerve guide.
AB  - Recovery of nerve function was evaluated after bridging a 15 mm sciatic nerve gap
      in 51 rats with a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve
      guide. Recovery of function was investigated by analysing the footprints, by
      analysing video recordings of gait, by electrically eliciting the withdrawal
      reflex, by nerve conduction velocity and by electromyography (EMG). Sensory nerve
      function recovered as measured by electrostimulation. Motor nerve function partly
      recovered but electromyograms remained abnormal throughout the study. We conclude
      that functional reinnervation by regenerating axons occurs after bridging a 15 mm
      nerve gap with a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide,
      but the walking patterns remain abnormal. Video analysis is a useful tool to
      record and analyse the walking patterns of rats. Further studies are necessary to
      investigate the possibility of obtaining selective reinnervation of specific
      muscles.

PMID- 14649684
TI  - Our experience using the vertical rectus abdominis muscle flap for reconstruction
      in 12 patients with dehiscence of a median sternotomy wound and mediastinitis.
AB  - The vertical rectus abdominis (VRAM) flap has been used for reconstruction of
      sternal defects, particularly in the inferior third, since it was first described
      20 years ago. We describe 12 patients with mediastinitis or chronic sternal
      osteomyelitis after sternotomy treated between 1994 and 1997, nine performed at
      the Royal Hospitals Trust, London. Sternal osteomyelitis and mediastinitis after
      median sternotomy is an uncommon (0.4%-8.4%) but often fatal condition.
      Vascularised pedicles are the treatment of choice, and VRAM flaps were used in
      all cases. We report good long-term outcome with a follow up of 2-5 years, and no
      long-term morbidity relating to the VRAM reconstruction. We had only one partial
      failure of a flap. The operations were largely done in hospitals away from the
      plastic surgical unit in extremely sick patients, which illustrates the
      importance of multidisciplinary management to reduce hospital stay, mortality,
      and morbidity. We argue that early involvement of plastic surgical specialists in
      the treatment of sternal dehiscence is essential to ensure a successful outcome.

PMID- 14649685
TI  - Management of cleft lip and palate in Brazil.
AB  - We aimed to evaluate the treatment protocols for cleft lip and palate that are
      used in Brazil, to compare them with the ones proposed from elsewhere, and to
      discuss the official data about admission for treatment of cleft lip or palate,
      or both, in Brazil. We also assessed the importance of integrated action of
      different specialities to treat this condition. A questionnaire related to
      attendance protocols was developed and sent out to all Brazilian Plastic Surgery
      Services connected to the Brazilian Society of Plastic Surgery, and to other
      units involved in such treatment. We also studied the data produced by the
      Brazilian Department of Health about the operations done during the past five
      years. Many protocols were identified, but despite much controversy in many
      areas, a consensus was reached about the surgical techniques, the age group most
      suitable to be operated on, and there was total agreement about the need for
      multidisciplinary management. According to the State Department of Health, the
      number of operations done in 1995 was 9696, and this had increased to 21 022 in
      1999. The state of Sao Paulo had done 17636 (84%) of all procedures in 1999.

PMID- 14649686
TI  - Immediate use of medicinal leeches to salvage venous congested reverse pedicled
      neurocutaneous flaps.
AB  - Reverse pedicled neurocutaneous flaps have recently become popular for
      reconstructing soft tissue defects of the lower extremity. Venous congestion is a
      relatively common problem in these flaps in diabetic patients and those with
      electric burns, and this may cause partial or complete loss if capillary
      perfusion is not re-established urgently. We describe our experience of 13
      neurocutaneous flaps, of which five developed venous congestion and were treated
      successfully with leeches placed immediately.

PMID- 14649687
TI  - Activation markers of connective tissue in Dupuytren's contracture: relation to
      postoperative outcome.
AB  - We investigated 103 consecutive patients operated on for Dupuytren's contracture
      (DC) to find out the relation between the expression of activation markers of
      connective tissue in surgical specimens obtained prospectively and recurrence of
      disease. The history of the disease and present state of the operated hand were
      obtained a mean of 4 years (range 2.5-6) after the latest operation.
      Immunohistochemical staining for anticollagen type IV, integrin alpha5, laminin,
      smooth muscle beta-actin, procollagen type I, and desmin was evaluated. Almost
      half of the patients noticed recurrences during the study period, one fifth
      within six months of operation. No differences in the expression of any of the
      markers investigated were found, either earlier or later than six months
      postoperatively, in patients with or without recurrent bending. Furthermore,
      there were no associations between sex, age at onset, number of operations,
      heredity, diabetes mellitus, or drugs taken for cardiovascular disease, and the
      expression of any of the immunohistochemical markers. The individual
      characteristics that place a person at high risk are not obviously related to
      ongoing production of connective tissue at the time of operation or to connective
      tissue activity in its conventionally-used sense.

PMID- 14649688
TI  - Combined imiquimod and acitretin for non-surgical treatment of basal cell
      carcinoma.
AB  - We report the successful outcome of treatment of a basal cell carcinoma (BCC)
      with topical imiquimod and systemic acitretin in a 48-year-old woman. We think
      that this treatment is a possible option for management of these non-life
      threatening tumours. Experimental evidence suggests that combination treatment
      with retinoids increase the effects of imiquimod and would therefore seem to be
      possible when treating superficial tumours in areas where the cosmetic outcome is
      particularly important.

PMID- 14649689
TI  - The long Abbe flap combined with periosteally-vascularised mandibular bone for
      the simultaneous reconstruction of the upper lip and supportive columella.
AB  - We did a simultaneous reconstruction of the upper lip and the supportive
      columella for a midface deformity caused by the wide resection of a squamous cell
      carcinoma of the nasal vestibule. It was reconstructed with an Abbe flap combined
      with a periosteally-vascularised outer layer of mandibular bone, which give an
      aesthetically and functionally acceptable result.

PMID- 14649690
TI  - Bilateral parotid sialoadenitis with gonial hypertrophy.
AB  - Sialoadenitis is a non-inflammatory condition that affects mainly the parotid,
      and is characterised by bilateral, painless swelling, which is an appreciable
      problem in young women. A 28-year-old woman presented with parotid sialoadenitis
      with masseteric hypertrophy. She was treated by superficial parotidectomy and
      ostectomy of the mandibular angle and made an uncomplicated recovery.

PMID- 14649691
TI  - Poland's syndrome with rare deformities: reconstruction with latissimus dorsi
      muscle through a single short incision.
AB  - We describe a 22-year-old man with Poland's syndrome and two other rare
      deformities which, to our knowledge have not been reported previously. The first
      deformity was a fibrotic band between the nipple-areola complex and the medial
      epicondyle of the humerus, and the second was a fifth digit with two phalanges. A
      single midaxillary vertical incision was used to harvest and then transfer the
      latissimus muscle for soft tissue reconstruction of the chest wall deformity.
      Almost complete symmetry was achieved and the scar was well hidden by the arm.
      The aesthetic and functional results were satisfactory.

PMID- 14649692
TI  - Proteus syndrome.
AB  - Proteus syndrome is a rare sporadic, hamartoneoplastic disorder of vascular,
      skeletal, and soft tissues that causes asymmetry of the skull, body, arms, and
      the legs. The name "Proteus" of the Greek god who had the ability to change his
      shape was coined to define the variety of deformities including partial gigantism
      of the hands or feet, asymmetry of the arms and legs, hypertrophy of long bones,
      plantar hyperplasia, haemangiomas, lipomas, varicosities, linear verrucous
      epidermal naevi, macrocephaly, and cranial hyperostoses. The basic defect seems
      to be the focal overgrowth of cellular elements in skin, bone, and other
      connective tissues. The variable features of the syndrome make differential
      diagnosis challenging for clinicians. The most important features are the
      hamartomatous disorders. The long-term prognosis is still not clear. As it is a
      hamartoneoplastic and incompletely delineated syndrome, the patients must be
      followed up because of the possible risk of neoplasms.

PMID- 14649693
TI  - Bilateral symptomatic supernumerary muscle belly syndrome.
AB  - A 32-year-old woman with a longstanding history of bilateral forearm pain had
      been unable to open her fingers and use her left arm (treated as reflex
      sympathetic dystrophy) since the age of 14. On physical examination there was
      fullness and tenderness of the distal volar forearms bilaterally; the quadriga
      test (when the patient was asked to make a tight fist quickly, with one finger
      fully extended passively) elicited burning pain. Operation confirmed that she had
      anomalous reversed forearm muscles bilaterally, and these were successfully
      resected.

PMID- 14649694
TI  - Recurrent salmonella osteomyelitis of both hands in a child with no signs of
      haemoglobinopathy: follow-up until 19 years of age.
AB  - Salmonella osteomyelitis is rare in children and usually occurs in conjunction
      with haemoglobinopathies. We followed a girl with recurrent salmonella
      osteomyelitis of both hands from infancy until she was 19 years of age. She was
      not affected by sickle cell disease, which sometimes accompanies acute swelling
      of hands and feet, and is known as hand-foot syndrome.

PMID- 14649695
TI  - Duplicate extensor tendons of the thumb mimicking rupture of the extensor
      pollicis longus tendon.
AB  - We report a patient with duplicate extensor pollicis longus tendons, who
      complained of inability to extend the thumb fully because of impingement of the
      musculotendinous junction of the duplicate tendons. Extension of the thumb
      recovered completely after Lister's tubercle was excised and the extensor
      retinaculum was released. Selective windowing with highlighting of the soft
      tissue in the axial T1-weighted magnetic resonance image at the level of the
      distal radioulnar joint showed two tendons in the third extensor compartment.

PMID- 14649696
TI  - Introduction. Lipids, inflammation and CVD--understanding the basics to break the
      atherosclerosis cycle.

PMID- 14649697
TI  - Dyslipidaemia versus endothelial dysfunction: which is more important in the
      development of vascular disease?

PMID- 14649698
TI  - Statins: how far have we come? A review of rosuvastatin.

PMID- 14649699
TI  - Statins: putting the benefit/risk into perspective.

PMID- 14649700
TI  - Global cardiovascular risk assessment: improving strategies in patients at
      intermediate risk.

PMID- 14649701
TI  - Dissipation of the herbicide clopyralid in an allophanic soil: laboratory and
      field studies.
AB  - Soil dissipation of the herbicide clopyralid (3,6-dichloropicolinic acid) was
      measured in laboratory incubations and in field plots under different management
      regimes. In laboratory studies, soil was spiked with commercial grade liquid
      formulation of clopyralid (Versatill, 300 g a.i. L(-1) soluble concentrate) @ 0.8
      microg a.i. g(-1) dry soil and the soil water content was maintained at 60% of
      water holding capacity of the soil. Treatments included incubation at 10 degrees
      C, 20 degrees C, 30 degrees C, day/night cycles (25/15 degrees C) and sterilized
      soil (20 degrees C). Furthermore, a field study was conducted at the Waikato
      Research Orchard near Hamilton, New Zealand starting in November 2000 to measure
      dissipation rates of clopyralid under differing agricultural situations. The
      management regimes were: permanent pasture, permanent pasture shielded from
      direct sunlight, bare ground, and bare ground shielded from direct sunlight.
      Clopyralid was sprayed in dilute solution @ 600 g a.i. ha(-1) on to field plots.
      Herbicide residue concentrations in soil samples taken at regular intervals after
      application were determined by gas chromatograph with electron capture detector.
      The laboratory experiments showed that dissipation rate of clopyralid was
      markedly faster in non-sterilized soil (20 degrees C), with a half-life (t1/2) of
      7.3 d, than in sterilized soil (20 degrees C) with t1/2 of 57.8 d, demonstrating
      the importance of micro-organisms in the breakdown process. Higher temperatures
      led to more rapid dissipation of clopyralid (t1/2, 4.1 d at 30 degrees C vs 46.2
      d at 10 degrees C). Dissipation was also faster in the day/night (25/15 degrees
      C) treatment (t1/2, 5.4 d), which could be partly due to activation of soil
      microbes by temperature fluctuations. In the field experiment, decomposition of
      clopyralid was much slower in the shaded plots under pasture (t1/2, 71.5 d) and
      bare ground (t1/2, 23.9 d) than in the unshaded pasture (t1/2, 5.0 d) and bare
      ground plots (t1/2, 12.9 d). These studies suggest that environmental factors
      such as temperature, soil water content, shading, and different management
      practices would have considerable influence on rate of clopyralid dissipation.

PMID- 14649702
TI  - The fate of 14C-diazinon in compost, compost-amended soil, and uptake by
      earthworms.
AB  - A process for disposing of pesticide rinsates using sorption onto organic matter
      followed by composting is being evaluated. As a part of this evaluation process,
      we have studied the bioavailability of composted delta-2-14C-diazinon and its
      degradation products to earthworms (Eisenia foetida Savigny) in 30 and 60 d
      compost amended soil. After 60 d of composting there was considerable degradation
      of diazinon (95%) and a corresponding increase in the primary hydrolysis product,
      2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP) as determined by high performance
      thin layer chromatography (HPTLC). Approximately 50% of the radioactivity became
      incorporated into the non-extractable fractions associated with composted organic
      matter with no measurable amounts of 14CO2 produced during the 60-day composting
      period. Following addition of the composted materials to soil, diazinon leading
      to 50% mortality after 14 d of exposure; continued to slowly degrade and become
      increasingly sorbed/entrapped within the soil-compost matrix. Soil amended with
      30-d composted diazinon was toxic to earthworms whereas, no mortality was
      observed in those earthworms exposed to the 60-d composted diazinon. However,
      earthworms exposed to 30-d and 60-d composted diazinon were found to have similar
      levels of radioactivity in their tissues. The majority of the radioactivity in
      earthworms exposed 60-d composted diazinon was either unextractably bound within
      the earthworm tissue or was not acetone soluble. Most of the radioactivity that
      could be extracted with acetone was not separated by the two HPTLC methods we
      used. This study demonstrates that composting high concentrations of diazinon can
      greatly reduce toxicity and the amount of diazinon that is bioavailable to a
      representative soil macroinvertebrate (E. foetida).

PMID- 14649703
TI  - The effect of propanil co-application on 2,4-D sorption by soil.
AB  - The herbicide 2,4-D is often applied as a tank mixture in combination with other
      herbicide products. However, current information on 2,4-D sorption by soil is
      largely based on batch-equilibrium experiments without considering the
      competition of other herbicides for sorption sites by soil. This study quantified
      the effect of the herbicide propanil on the sorption of 2,4-D in soil. Results
      indicated that propanil competed with 2,4-D for sorption sites, particularly in
      soils with an organic carbon content greater than 3.6%. The decrease in 2,4-D
      sorption by soil, as a result of propanil competition, was most notably for
      herbicide concentrations that are typical of recommended field rates. We conclude
      that herbicide co-applications on agricultural fields have the potential to
      increase the mobility of herbicides in soil.

PMID- 14649704
TI  - Persistence of phorate in soils: role of moisture, temperature, preexposure, and
      microorganisms.
AB  - In laboratory incubation studies with three soils of varying physicochemical
      characteristics, phorate was more persistent in nonflooded (60% water holding
      capacity) soils than in flooded soils. Phorate sulphoxide was recovered as the
      only metabolite of phorate in nonflooded soils while three metabolites (diethyl
      dithiophosphate, triethyl dithiophosphate and an unidentified metabolite) were
      formed in flooded soils. Study indicates that in nonflooded soils phorate is
      degraded via oxidation while in flooded soils hydrolysis is the major degradation
      process. Degradation of phorate was accelerated by an increase in incubation
      temperature. Preexposure or repeated application of soils to phorate slightly
      decreased the persistence of phorate or its metabolites. Decreased persistence of
      phorate and its metabolites formed in nonsterile soils compared to sterile soils
      suggested the role of microorganisms in their transformation.

PMID- 14649705
TI  - Biodegradation of chlorsulfuron and metsulfuron-methyl by Aspergillus niger in
      laboratory conditions.
AB  - Two sulfonylurea herbicides, chlorsulfuron and metsulfuron-methyl, were studied
      under laboratory conditions, in order to elucidate the biodegradation pathway
      operated by Aspergillus niger, a common soil fungus, which is often involved in
      the degradation of xenobiotics. HPLC-UV was used to study the kinetic of
      degradation, whereas LC-MS was used to identify the metabolites structure. In
      order to avoid the chemical degradation induced by a decrease in pH, due to the
      production of citric acid by the fungus, the experiments were performed in a
      buffered neutral medium. No significant degradation for both compounds was
      observed in mineral medium with 0.2% sodium acetate. On the contrary, in a rich
      medium, after 28 days the degradations, chemical degradation excluded, were about
      30% for chlorsulfuron and 33% for metsulfuron-methyl. The main microbial
      metabolites were obtained via cleavage of the sulfonylurea bridge. In addition
      the fungus seems to be able to hydroxylate the aromatic ring of chlorsulfuron. In
      the case of metsulfuron-methyl the only detected metabolite was the triazine
      derivative, while the aromatic portion was completely degraded. Finally, the
      demethylation of the methoxy group on the triazine ring, previously observed with
      a Pseudomonas fluorescens strain, was not observed with A. niger.

PMID- 14649706
TI  - Light and clomazone effects on tobacco (Nicotiana tabacum) callus and leaf discs.
AB  - The effects of clomazone on the growth of tobacco (Nicotiana tabacum L. 'NC2326')
      callus and leaf discs were studied under four light regimes. Callus cultures and
      leaf discs were grown on Murashige and Skoog medium supplemented with IAA and
      kinetin. Light regimes were: dark grown callus kept in the dark and also
      transferred to the light; light grown callus kept in the light and also
      transferred to the dark. Two-month-old callus (cultured for 2 months from
      initiation) grew more rapidly than twelve-month-old callus (cultured for 12
      months from initiation) under all conditions tested. Callus transferred from
      light to dark, or from dark to light, increased in fresh weight slower than did
      the callus maintained totally in light or dark. Clomazone (2-[(2
      chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone) at 140 mg l(-1) or more was
      lethal to both callus and leaf discs whereas 10 mg l(-1) was stimulatory to
      growth. Callus tissue responded to clomazone differently depending on the light
      regime under which it was grown. While clomazone may be affecting the isoprenoid
      pathway in the callus and leaf disks resulting in growth inhibition, it is
      possible that other target sites are also being affected and contribute to the
      reduced growth.

PMID- 14649707
TI  - Field efficacy and baseline toxicities of pyriproxifen, acetamiprid, and
      diafenthiuron against Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) in
      Burkina Faso (West Africa).
AB  - Bioassays were conducted in 2001 and 2002 to estimate toxicities and dose
      response relationships of 24 Bemisica tabaci Gennadius populations to
      pyriproxifen, acemitaprid, and diafenthiuron. LC50s ranging from 0.014 to 0.096
      mgL(-1), 0.60 to 1.3 mgL(-1), and 3.5 to 6.7 mgL(-1) were observed respectively
      for pyriproxifen, acemitaprid, and diafenthiuron. These LC50s much lower than the
      field doses recommended for each compound. A fast increase in rates of mortality
      within a narrow range of lethal concentrations was observed for each compound.
      indicating that all three compounds were highly effective at killing whiteflies.
      In a separate experiment, pyriproxifen, acemitaprid, and diafenthiuron were
      tested in 2001 and 2002 to compare their effectiveness and assess their impact on
      parasitism in the field. In both years all three compounds significantly
      prevented B. tabaci populations from reaching economic injury levels in cotton
      and minimized adverse effects on parasitism. Our results provide for the first
      time baseline toxicological, field efficacy, and effect on parasitism data for
      pyriproxifen, acemitaprid, and diafenthiuron against B. tabaci in West Africa.
      These compounds should be included in a resistance management program of the
      cotton pest complex and their use should be restricted to prevent the building of
      resistance in B. tabaci populations.

PMID- 14649708
TI  - Phylogenetic and degradation characterization of Burkholderia cepacia WZ1
      degrading herbicide quinclorac.
AB  - Strain WZI capable of degrading quinclorac was isolated from a pesticide
      manufactory soil and considered to be Burkholderia cepacia, belonged to bacteria,
      Proteobacteria, beta-Proteobacteria, based on morphology, physio-biochemical
      properties, whole cell fatty acid analysis and a partial sequencing of 16S rDNA.
      Strain WZ1 decomposed 90% of quinclorac at original concentration of 1000 mg L(
      1) within 11 days. GC/MS analysis showed that the strain degraded quinclorac to
      3,7-dichloro-8-quinoline and the cracked residue 2-chloro, 1,4
      benzenedicarboxylic acid, indicating that the metabolic pathway was initiated by
      process of decarboxylation followed by cleavage of the aromatic ring. Stain WZ1
      was also able to degrade some other herbicides and aromatic compounds, including
      2,4,5-T, phenol, naphthalene and hydrochinone etc. This paper describes for the
      first time Phylogenetic and degradation characterization of a pure bacterium
      which, is able to mineralize quinclorac.

PMID- 14649709
TI  - Isolation and 16S DNA characterization of soil microorganisms from tropical soils
      capable of utilizing the herbicides hexazinone and tebuthiuron.
AB  - Six non-fermentative bacteria were isolated from Colombian (South America) and
      Hawaiian (USA) soils after enrichment with minimal medium supplemented with two
      herbicides, hexazinone (Hex) and tebuthiuron (Teb). Microscopic examination and
      physiological tests were followed by partial 16S DNA sequence analysis, using the
      first 527 bp of the 16S rRNA gene for bacterial identification. The isolated
      microorganisms (and in brackets, the herbicide that each degraded) were
      identified as: from Colombia. Methylobacterium organophilum [Teb], Paenibacillus
      pabuli [Teb], and Micrmbacterium foliorum [Hex]; and from Hawaii,
      Methylobacterium radiotolerans [Teb], Paenibacillus illinoisensis [Hex], and
      Rhodococcus equi [Hex]. The findings further explain how these herbicides, which
      have potential for illicit coca (Erythroxylum sp.) control, dissipate following
      their application to tropical soils.

PMID- 14649710
TI  - Degradation of soil environment in the post-flooding area: content of polycyclic
      aromatic hydrocarbons (PAHs) and s-triazine herbicides.
AB  - Impacts of flooding on the soil environment with regard to soil pollution with
      polycyclic aromatic hydrocarbons and s-triazine (cyanazine, simazine, atriazine,
      propazine, prometryn) herbicides have been evaluated. No clear differences in the
      sum of the PAHs content were observed in the present studies. Only changes in the
      levels of individual PAHs were noted. In soils covered with flooding both at a
      depth of 0-20 and 20-40 high molecular weight PAHs were predominant (especially
      mutagenic and carcinogenic 5-rings PAHs) whereas in non-flooded areas, 2- and 3
      rings PAHs constituted over 80%. In the case of s-triazine herbicides, no
      influence of flooding on the changes in their content in agriculturally used
      soils was noted. On the other hand, clearly lower levels of cyanazine, simazine
      and atriazine were not in the flooded forest soil as compared to the non-flooded
      forest soil.

PMID- 14649711
TI  - Removal of MCPA from aqueous solutions by acid-activated spent bleaching earth.
AB  - The removal of MCPA (4-chloro-2-methyl phenoxyacetic acid) from aqueous solutions
      by activated spent bleaching earth (SBE) was studied as a function of time,
      initial concentration, adsorbent concentration, and temperature. The Langmuir and
      Freundlich isotherms were fitted by the adsorption data obtained. The values of
      Langmuir and Freundlich constants were determined. The adsorption kinetics was
      described by the Lagergren equation. Mass transfer coefficient and thermodynamic
      parameters were also calculated. Column experiments were conducted and
      brekthrough capacities were found for different concentrations and different flow
      rates. The study demonstrates that acid-treated SBE could be used as an efficient
      adsorbent for the removal of MCPA-bearing wastewater effluents.

PMID- 14649712
TI  - Enhanced desorption of phenanthrene from soils using hydroxypropyl-beta
      cyclodextrin: experimental results and model predictions.
AB  - Objective of this study was to evaluate the effects of hydroxypropyl-beta
      cyclodextrin (HPCD) on the removal of phenanthrene from solid phase. Batch tests
      for the phenanthrene distribution between aqueous and solid phase were conducted
      in the presence of HPCD. Column tests and numerical simulations were conducted to
      evaluate the roles of HPCD cavities and interaction rates between water, HPCD,
      and solid phase in the enhanced removal of phenanthrene. Experimental results
      showed that HPCD was effective in removing sorbed phenanthrene from subsurface
      environment, primarily due to its negligible sorption to the solid phase and the
      partitioning of phenanthrene into HPCD cavities. From the numerical simulations,
      it was found that rate-limited partitioning of phenanthrene into HPCD cavities
      was most influential factor in the enhanced elution of phenanthrene. Sorption and
      desorption rate of phenanthrene between aqueous and solid phase was very fast or
      near equilibrium state. Interaction rates of contaminant between water, HPCD, and
      solid phase could be affected by other factors such as soil types and organic
      matter contents. Results from this study implied that HPCD flushing could be
      effectively applied for the removal of hydrophobic organic pollutants existing in
      the soils as sorbed or NAPL state.

PMID- 14649713
TI  - Ozonation of aqueous solution of alpha endosulfan.
AB  - Ozonation of alpha endosulfan and the effects of some parameters such as pH,
      temperature and partial pressure on ozonation were investigated and the kinetic
      constants were calculated in this study. Alpha endosulfan solutions were ozonated
      in a lab-scale semi-batch reactor under variable experimental conditions.
      Increase in dissolved ozone concentration had a positive effect on oxidation
      rate. Alpha endosulfan could be removed up to 94% at pH 4 for an ozonation time
      of 60 minutes. The oxidation reaction was found to be of second order and of
      first order with respect to both ozone and alpha endosulfan. The temperature
      dependent reaction expression of alpha endosulfan was obtained as kd = (1.889
      exp(- 2.21 x 10(-3)/T). It was concluded that, although the rate of reaction was
      lower than the rate of other pesticide oxidation reported in the literature.
      alpha endosulfan presented an obvious reaction to ozonation.

PMID- 14649714
TI  - Benefits of sustainable waste management in the vegetable greenhouse industry.
AB  - This study investigated the benefits of an on-site sustainable solid waste
      treatment and utilization system for the greenhouse industry. The composts made
      from greenhouse wastes were tested and found to contain high nutrient values and
      good physical properties, and could be used as high quality growing media. The
      finished composts were tested in a greenhouse against the conventional growth
      media (sawdust) and resulted in a 10% yield increase by using the compost. An
      economic analysis was conducted to show the economic benefits of on-site
      composting for a greenhouse operation. Based on a four-hectare tomato or pepper
      greenhouse, and amortizing the capital equipment over five years, the net annual
      cost of composting represents a savings of dollars 8,000 annually.

PMID- 14649715
TI  - Effects of soil amendments at a heavy loading rate associated with cover crops as
      green manures on the leaching of nutrients and heavy metals from a calcareous
      soil.
AB  - The potential risk of groundwater contamination by the excessive leaching of N, P
      and heavy metals from soils amended at heavy loading rates of biosolids, coal
      ash, N-viro soil (1:1 mixture of coal ash and biosolids), yard waste compost and
      co-compost (3:7 mixture of biosolids to yard wastes), and by soil incorporation
      of green manures of sunn hemp (Crotalaria juncea) and sorghum sudangrass (Sorghum
      bicolor x S. bicolor var. sudanense) was studied by collecting and analyzing
      leachates from pots of Krome very gravelly loam soil subjected to these
      treatments. The control consisted of Krome soil without any amendment. The
      loading rate was 205 g pot(-1) for each amendment (equivalent to 50 t ha(-1) of
      the dry weight), and the amounts of the cover crops incorporated into the soil in
      the pot were those that had been grown in it. A subtropical vegetable crop, okra
      (Abelmoschus esculentus L.), was grown after the soil amendments or cover crops
      had been incorporated into the soil. The results showed that the concentration of
      NO3-N in leachate from biosolids was significantly higher than in leachate from
      other treatments. The levels of heavy metals found in the leachates from all
      amended soils were so low, as to suggest these amendments may be used without
      risk of leaching dangerous amounts of these toxic elements. Nevertheless the
      level of heavy metals in leachate from coal ash amended soil was substantially
      greater than in leachates from the other treatments. The leguminous cover crop,
      sunn hemp, returned into the soil, increased the leachate NO3-N and inorganic P
      concentration significantly compared with the non-legume, sorghum sudangrass. The
      results suggest that at heavy loading rates of soil amendments, leaching of NO3-
      could be a significant concern by application of biosolids. Leaching of inorganic
      P can be increased significantly by both co-compost and biosolids, but decreased
      by coal ash and N-viro soil by virtue of improved adsorption. The leguminous
      cover crop, sunn hemp, when incorporated into the soil, can cause the
      concentration of NO3-N to increase by about 7 fold, and that of inorganic P by
      about 23% over the non-legume. Regarding the metals, biosolids, N-viro soil and
      coal ash significantly increased Ca and Mg concentrations in leachates. Copper
      concentration in leachate was increased by application of biosolids, while Fe
      concentration in leachates was increased by biosolids, coal ash and co-compost.
      The concentrations of Zn, Mo and Co in leachate were increased by application of
      coal ash. The concentrations of heavy metals in leachates were very low and
      unlikely to be harmful, although they were increased significantly by coal ash
      application.

PMID- 14649716
TI  - Changes of the level of G protein alpha-subunit mRNA by tolerance to and
      withdrawal from butorphanol.
AB  - Butorphanol was infused continuously into cerebral ventricle at a constant rate
      of 26 nmol/microl/h for 3 days, and the withdrawal from opioid was rendered 7 h
      after the cessation of infusion. The G-protein alpha-subunit has been implicated
      in opioid tolerance and withdrawal. The effects of continuous infusion of
      butorphanol on the modulation of G protein alpha-subunit mRNA were investigated
      by using in situ hybridization techniques. In situ hybridization showed marked
      changes in the levels of Galpha s during butorphanol tolerance and withdrawal.
      Specifically, the level of Galpha s mRNA was significantly decreased in almost
      all areas of brain except hippocampus during the butorphanol withdrawal. It was
      also decreased in the septum and cerebellar granule layer in butorphanol tolerant
      rats. The level of Galpha i mRNA was significantly decreased only in the cerebral
      cortex of butorphanol tolerant rat. However, no such change was noted during the
      withdrawal from butorphanol. The level of Galpha o mRNA was not changed either in
      butorphanol tolerant or in the butorphanol withdrawal rats. No alterations were
      noted in the level of [3H]forskolin binding to adenylyl cyclase in butorphanol
      tolerant as well as withdrawing rats. The levels of pCREB were significantly
      elevated in the hippocampus in the butorphanol withdrawal rats. These results
      suggest that region-specific changes of G protein alpha-subunit mRNA and pCREB
      without marked changes in the level of adenylyl cyclase may underlie the
      tolerance to and withdrawal from butorphanol.

PMID- 14649717
TI  - Possible involvement of astrocytes in neuroprotection by the cognitive enhancer T
      588.
AB  - We have previously shown that the cognition enhancer (1R)-1-benzo[b]thiophen-5-yl
      2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588) protects astrocytes
      against hydrogen peroxide (H2O2) injury via activation of extracellular signal
      regulated kinase (ERK) pathway. The present study examines whether the effect of
      T-588 on astrocytes contributes to neuroprotection in neuronal injury models.
      Astrocyte-conditioned medium (ACM) protected against neuronal injury induced by
      amyloid-beta protein (A beta) in cultured cortical neurons. The effect of ACM on
      A beta-induced injury was blocked by the ERK kinase inhibitor 2'-amino-3'
      methoxyflavone. ACM stimulated ERK phosphorylation in cultured neurons. ACM
      derived from astrocytes exposed to H2O2 lost the activities to stimulate ERK
      phosphorylation and protect against neuronal injury. T-588 blocked the H2O2
      induced loss of the activities of ACM. These results suggest that ACM protects
      against neuronal injury by an ERK-dependent mechanism, and the effect of T-588 on
      astrocytic injury results in neuroprotection.

PMID- 14649718
TI  - Inhibitory effects of Bombusae concretio Salicea on neuronal secretion of
      Alzheimer's beta-amyloid peptides, a neurodegenerative peptide.
AB  - Alzheimer's disease (AD) is characterized by the age-related deposition of beta
      amyloid (A beta) 40/42 peptide aggregates in vulnerable brain regions. Multiple
      levels of evidence implicate a central role for A beta in the pathophysiology of
      AD. A beta is generated by the regulated cleavage of a = 700 amino acid A beta
      precursor protein (betaAPP). Full-length betaAPP can undergo proteolytic cleavage
      either within the A beta domain to generate secreted sbetaAPP alpha or at the N
      terminal and C-terminal domain(s) of A beta to generate amyloidogenic A beta
      peptides. Several epidemiological studies have reported that estrogen replacement
      therapy protects against the development of AD in postmenopausal women. The aim
      of this study was to elucidate the antioxidant neuroprotective mechanism of
      Bombusae concretio Salicea (BC). BC was effective protectants against oxidative
      glutamate toxicity in the murine neuroblastoma cells (N2a) and human
      neuroblastoma cells (SK-N-MC). BC exhibited similar protective properties against
      oxidative glutamate toxicity and H2O2 toxicity. BC exhibited an antioxidant
      activity at approximately 20 microg/ml. BC of 5 microg/ml was ineffective in
      preventing the oxidative modification of LDL. The half-maximal effective
      concentration for BC was 16 microg/ml. These results suggested that BC
      supplementation in elderly men may be protective in the treatment of Alzheimer's
      disease (AD). We report here that treatment with BC increases the secretion of
      the nonamyloidogenic APP fragment, sbetaAPP alpha and decreases the secretion of
      A beta peptides from N2a cells and rat primary cerebrocortical neurons. These
      results raise the possibility that BC supplementation in elderly men may be
      protective in the treatment of AD.

PMID- 14649719
TI  - Ketogenic diet increases glutathione peroxidase activity in rat hippocampus.
AB  - Ketogenic diets have been used in the treatment of refractory childhood epilepsy
      for almost 80 years; however, we know little about the underlying biochemical
      basis of their action. In this study, we evaluate oxidative stress in different
      brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to
      have not been affected by this diet, and cerebellum presented a decrease in
      antioxidant capacity measured by a luminol oxidation assay without changes in
      antioxidant enzyme activities--glutathione peroxidase, catalase, and superoxide
      dismutase. In the hippocampus, however, we observed an increase in antioxidant
      activity accompanied by an increase of glutathione peroxidase (about 4 times) and
      no changes in lipoperoxidation levels. We suggest that the higher activity of
      this enzyme induced by ketogenic diet in hippocampus might contribute to protect
      this structure from neurodegenerative sequelae of convulsive disorders.

PMID- 14649720
TI  - Effects of metabotropic glutamate receptor stimulation on cerebral O2 consumption
      and blood flow during focal cerebral ischemia in rats.
AB  - This investigation was performed to evaluate the effects of ACPD [(1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid], a metabotropic glutamate receptor
      agonist, on cerebral O2 consumption during focal cerebral ischemia. Male Wistar
      rats were placed in control (n = 7) and ACPD (n = 7) groups under isoflurane
      anesthesia. Twenty minutes after middle cerebral artery (MCA) occlusion, gauze
      sponges with 10(-5) M ACPD or normal saline were placed on the ischemic cortex
      (IC) for a period of 40 min and were changed every 10 min. One hour after MCA
      occlusion, regional cerebral blood flow (rCBF) was determined using the C14
      iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen
      saturation were determined using microspectrophotometry. There were no
      statistical differences in vital signs, blood gases, and hemoglobin between the
      groups. In the control group, the cerebral blood flow and oxygen consumption of
      the IC were significantly lower than the contralateral cortex (rCBF: 45 +/- 11
      vs. 110 +/- 11 ml/min/100 g, O2 consumption: 2.9 +/- 0.4 vs. 5.4 +/- 1.1 ml
      O2/min/100 g). ACPD did not change regional cerebral blood flow of the IC, but
      did significantly increase the oxygen extraction (7.8 +/- 0.2 vs. 6.9 +/- 0.3 ml
      O2/100 ml) and oxygen consumption of the IC (4.3 +/- 1.5 vs. 2.9 +/- 0.4)
      compared to the control IC. Our data demonstrated that topical application of 10(
      5) M ACPD to the ischemic area worsened cerebral O2 balance. These data suggest
      that metabotropic glutamate receptors are not maximally activated during ischemia
      in the temporal cortex.

PMID- 14649722
TI  - Structural specificity for the inhibitory effect of calmodulin on specific 125I
      omega-conotoxin GVIA binding.
AB  - To clear the structural specificity of calmodulin (CaM) on the specific 125I
      omega-CTX binding to crude membranes from whole chick brain, the following
      experiments were investigated in this study: (i) the attenuating effect of
      semisynthetic tetrahydroisoquinoline derivatives on the inhibitory effect of
      Ca2+/CaM, (ii) the effects of chimeras of yeast and chicken Ca2+/CaM, and (iii)
      the effects of Ca2+-binding proteins (such as troponin c, S 100 a and b, and
      annexin I, III-V). The inhibitory effect of Ca2+/CaM was attenuated by
      isoquinoline derivatives (PX 28, 34, 216, 224, and CPU57) and a CaM antagonist W
      7. PX 34, a typical synthesized isoquinoline derivative, showed the attenuating
      effect in a dose-dependent manner. The ED50 value for the attenuating effect of
      PX 34 was about 20 microM, which is similar to that of W-7 reported previously.
      Some chimeric CaMs such as YC 51-53 (which are close to the properties of
      vertebrate CaM) showed a significant inhibitory effect on the specific 125I-omega
      CTX binding, but YC 129 and 130 (which retain the properties of yeast CaM),
      troponin c, S100 a, b, and annexin I, III-V had no effect on the specific 125I
      omega-CTX binding. These results suggest that the characteristic structure
      containing the EF-hand structure of CaM itself is needed to cause the inhibitory
      effect on the specific 125I-omega-CTX binding.

PMID- 14649721
TI  - Reduction of mitochondrial electron transport complex activity is restricted to
      the ischemic focus after transient focal cerebral ischemia in rats: a
      histochemical volumetric analysis.
AB  - Using histochemical methods offering high topographical resolution for evaluation
      of changes in the ischemic focus and the penumbra, the mitochondrial electron
      transport chain (ETC) complexes I, II, and IV were examined in rats subjected to
      2 h of proximal occlusion of the middle cerebral artery (MCAO) followed by no
      reperfusion, 1 h reperfusion, 4 h reperfusion, or 4 h reperfusion plus treatment
      with the free radical scavenger alpha-PBN. Serial brain cryosections were
      histochemically stained to visualize activity of complexes I, II, and IV, and the
      volumes of tissue with reduced activity in the ipsilateral cortex and caudate
      putamen were measured by densitometric image analysis. Reductions in complex I,
      II, and IV activity were restricted to areas in the ischemic foci in cortex and
      caudate putamen, which microscopically displayed signs of early morphological
      damage. In cortex, the tissue volume with reduced activity did not change
      significantly during reperfusion but progressively increased in the caudate
      putamen, possibly reflecting a faster maturation of morphological damage in this
      region. Treatment with alpha-PBN did not affect the observed reductions in
      activities. We deduce that inhibition of mitochondrial ETC complex activity does
      not play a critical role for recruitment of the penumbra in the infarction
      process.

PMID- 14649723
TI  - Effects of activation of NMDA and AMPA glutamate receptors on the extracellular
      concentrations of dopamine, acetylcholine, and GABA in striatum of the awake rat:
      a microdialysis study.
AB  - The effects of activation of the AMPA and NMDA ionotropic glutamate receptors on
      the extracellular concentration of dopamine, acetylcholine, (ACh) and GABA in
      striatum of the awake rat was investigated. Also the levels of DOPAC, HVA, and
      choline (Ch) were included in this study. Seven to eight days after stereotaxical
      implantation of a guide-cannulae assembly, microdialysis experiments were
      performed. The dopamine and ACh content of samples were measured by HPLC coupled
      to electrochemical detection. GABA was measured using fluorometric detection.
      Perfusion of AMPA (1, 20, 100 microM) produced a dose-related increase of
      dopamine and a dose-related decrease of DOPAC and HVA. AMPA 100 microM decreased
      extracellular concentrations of ACh and increased the extracellular concentration
      of Ch and GABA. Perfusion of NMDA 500 microM increased the concentration of
      dopamine and decreased DOPAC and HVA. Also, NMDA 100 microM decreased DOPAC. NMDA
      500 microM decreased the extracellular concentrations of ACh and increased the
      concentrations of Ch and GABA. Perfusion of the AMPA/kainate-antagonist DNQX (100
      microM) blocked the effects of AMPA (100 microM) on dopamine, DOPAC, HVA, ACh,
      and GABA concentrations. Perfusion of the NMDA-antagonist CPP (100 microM)
      blocked the effects of NMDA 500 microM on dopamine, DOPAC, HVA, ACh, Ch, and GABA
      concentrations. These results suggest an interaction between glutamate-dopamine
      ACh-GABA in striatum of the awake rat.

PMID- 14649724
TI  - T-588 protects motor neuron death against glutamate-induced neurotoxicity.
AB  - To examine the possible neuroprotective effect of T-588 against glutamate-induced
      neurotoxicity, we analyzed the pharmacological utility of T-588 in a postnatal
      organotypic culture model of motor neuron degeneration. Treatment with 10(-5) M
      of glutamate resulted a motor neuron loss and decreased activity of choline
      acetyltransferase (ChAT). Cotreatment of 10(-5) M of glutamate and T-588 revealed
      a protective effect against motor neuron death and decreased ChAT activity. We
      concluded that T-588 may play important roles in the survival and maintenance of
      spinal motor neurons in its neuroprotection against glutamate-induced
      neurotoxicity. Our data may provide a rationale for designing a therapeutic
      strategy for protection against pathologically induced motor neuron damage or
      cell death such as amyotrophic lateral sclerosis and motor neuropathy.

PMID- 14649725
TI  - Antioxidant effect of phenelzine on MPP+-induced cell viability loss in
      differentiated PC12 cells.
AB  - Phenelzine, deprenyl, and antioxidants (SOD, catalase, ascorbate, or rutin)
      reduced the loss of cell viability in differentiated PC12 cells treated with 250
      microM MPP+, whereas N-acetylcysteine and dithiothreitol did not inhibit cell
      death. Phenelzine reduced the condensation and fragmentation of nuclei caused by
      MPP+ in PC12 cells. Phenelzine and deprenyl prevented the MPP+-induced decrease
      in mitochondrial membrane potential, cytochrome c release, formation of reactive
      oxygen species, and depletion of GSH in PC12 cells. Phenelzine revealed a
      scavenging action on hydrogen peroxide and reduced the hydrogen peroxide-induced
      cell death in PC12 cells, whereas deprenyl did not depress the cytotoxic effect
      of hydrogen peroxide. Both compounds reduced the iron and EDTA-mediated
      degradation of 2-deoxy-D-ribose degradation. The results suggest that phenelzine
      attenuates the MPP+-induced viability loss in PC12 cells by reducing the
      alteration of mitochondrial membrane permeability that seems to be mediated by
      oxidative stress.

PMID- 14649726
TI  - Regulation of the Na+-dependent glutamate/aspartate transporter in rodent
      cerebellar astrocytes.
AB  - The regulation of the Na+-dependent glutamate/aspartate transporter system GLAST
      expressed in rat and mouse cerebellar and cortical astrocytic cultures was
      examined. Pretreatment of the cerebellar cells with L-glutamate and 12-O
      tetradecanoyl-phorbol-13-acetate (TPA), a known Ca2+/diacylglicerol-dependent
      protein kinase (PKC) activator, produced a decrease in [3H]-D-aspartate uptake.
      This reduction was dose- and time-dependent and sensitive to PKC inhibitors.
      Furthermore, the L-glutamate-dependent [3H]-D-aspartate uptake decrease is a non
      receptor dependent process, because neither of the agonists or antagonists were
      effective in mimicking or reverting the effect. Interestingly, transportable
      substrates could reproduce the L-glutamate effect. In sharp contrast, in cortical
      astrocytes, both L-glutamate and TPA pre-exposure result in an augmentation of
      the [3H]-D-aspartate uptake. These findings suggest that the Na+-dependent
      glutamate uptake GLAST undergoes a region-specific regulation.

PMID- 14649727
TI  - Ornithine decarboxylase activity in in vivo and in vitro models of cerebral
      ischemia.
AB  - Ornithine decarboxylase (ODC) is considered the rate-limiting enzyme in polyamine
      biosynthesis, and an increase in putrescine after central nervous system (CNS)
      injury appears to be involved in neuronal death. Cerebral ischemia and
      reperfusion trigger an active series of metabolic events, which eventually lead
      to neuronal death. In the present study, ODC activity was evaluated following
      transient focal cerebral ischemia and reperfusion in rat. The middle cerebral
      artery (MCA) was occluded for 2 h in male rats with an intraluminal suture
      technique. Animals were sacrificed between 3 and 48 h of reperfusion following
      MCA occlusion, and ODC activity was assayed in cortex and striatum. ODC activity
      was also estimated in an in vitro ischemia model using primary rat cortical
      neuron cultures, at 6-24 h reoxygenation following 1 h oxygen-glucose deprivation
      (OGD). In cortex, following ischemia, ODC activity was increased at 3 h (P <
      .05), reached peak levels by 6-9 h (P < .001) and returned to sham levels by 48 h
      reperfusion. In striatum the ODC activity followed a similar time course, but
      returned to basal levels by 24 h. This suggests that ODC activity is upregulated
      in rat CNS following transient focal ischemia and its time course of activation
      is region specific. In vitro, ODC activity showed a significant rise only at 24 h
      reoxygenation following ischemic insult. The release of lactate dehydrogenase
      (LDH), an indicator for cell damage, was also significantly elevated after OGD.
      0.25 mM alpha-difluoromethylornithine (DFMO) inhibited ischemia-induced ODC
      activity, whereas a 10-mM dose of DFMO appears to provide some neuroprotection by
      suppressing both ODC activity and LDH release in neuronal cultures, suggesting
      the involvement of polyamines in the development of neuronal cell death.

PMID- 14649728
TI  - Interaction between metals and chelating agents affects glutamate binding on
      brain synaptic membranes.
AB  - The present study investigates the possible effects of Hg2+, Pb2+, and Cd2+ on
      [3H]-glutamate binding. To better understand the role of the thiol-disulfide
      status on the toxicity of such metals toward glutamatergic neurotransmission, we
      used three thiol chelating agents, 2,3-dimercaptopropanol (BAL), 2,3
      dimercaptopropane 1-sulfonate (DMPS), and meso-2,3-dimercaptosuccinic acid
      (DMSA). Dithiotreitol (DTT) was tested for its ability to prevent metals-induced
      inhibition on [3H]-glutamate binding. Hg2+, Pb2+, and Cd2+ showed a concentration
      dependent inhibition on [3H]-glutamate binding, and mercury was the most
      effective inhibitor. BAL did not prevent [3H]-glutamate binding inhibition by
      Hg2+, Cd2+, and Pb2+. However, DMPS and DMSA prevented the inhibition caused by
      Cd2+ and Pb2+, but not by Hg2+. DTT did not prevent the inhibition on [3H]
      glutamate binding caused by 10 microM Hg2+. In contrast, it was able to partially
      prevent [3H]-glutamate binding inhibition caused by 40 microM Pb2+ and Cd2+.
      These results demonstrated that the heavy metals present an inhibitory effect on
      [3H]-glutamate binding. In addition, BAL was less effective to protect [3H]
      glutamate binding inhibition caused by these metals than other chelating agents
      studied.

PMID- 14649729
TI  - Effect of hypothalamic proline-rich-polypeptide on voltage-gated Ca2+ currents in
      retinal ganglion cells.
AB  - Neurotrophins are molecules that regulate neuronal survival, nervous system
      plasticity, and many other physiological functions of neuronal and glial cells.
      Here we studied the physiological action of a novel neurosecretory polypeptide
      proline-rich polypeptide (PRP), isolated from bovine neurohypophysis
      neurosecretory granules, on voltage-gated Ca currents and spike firing activity
      of retinal ganglion cells. PRP reversibly increased high voltage-activated L-type
      Ca current, but was without effect on low voltage-activated T-type current. PRP
      also increased the spike after hyperpolarization and reduced the frequency of
      spike firing, most likely by affecting a Ca-dependent potassium current.

PMID- 14649730
TI  - cDNA microarray analysis of changes in gene expression associated with MPP+
      toxicity in SH-SY5Y cells.
AB  - cDNA microarray analysis of 1-methyl-4-phenyl-pyridinium (MPP+) toxicity (1 mM,
      72 h) in undifferentiated SH-SY5Y cells identified 48 genes that displayed a
      signal intensity greater than the mean of all differentially expressed genes and
      a two-fold or greater difference in normalized expression. RT-PCR analysis of a
      subset of genes showed that c-Myc and RNA-binding protein 3 (RMB3) expression
      decreased by approximately 50% after 72 h of exposure to MPP+ (1 mM) but did not
      change after 72 h of exposure to 6-hydroxydopamine (25 microM), rotenone (50 nM),
      and hydrogen peroxide (600 microM). Exposure of retinoic acid (RA)-differentiated
      SH-SY5Y cells to MPP+ (1 mM, 72 h) also resulted in a decrease in RMB3 expression
      and an increase in GADD153 expression. In contrast, c-Myc expression was slightly
      increased in RA-differentiated cells. Collectively, these data provide new
      insights into the molecular mechanisms of MPP+ toxicity and show that MPP+ can
      elicit distinct patterns of gene expression in undifferentiated and RA
      differentiated SH-SY5Y cells.

PMID- 14649731
TI  - Nitration of the striatal Na,K-ATPase alpha3 isoform occurs in normal brain
      development but is not increased during hypoxia-ischemia in newborn piglets.
AB  - Neonatal hypoxia-ischemia (HI) can result in significant sensorimotor
      abnormalities, including movement and posture disorders. These neurological
      impairments are believed to result from basal ganglia (striatum) damage, but the
      exact cause of this injury is not known. One mechanism involved in brain injury
      after HI is the generation of reactive oxygen species, which damage cellular
      macromolecules. We tested the hypothesis that inactivation of plasma membrane
      enzyme Na,K-ATPase during striatal neurodegeneration after HI emerges with
      peroxynitrite attack on the enzyme. In vitro, reaction of peroxynitrite (100-500
      microM) with purified Na,K-ATPase produced nitration of the alpha (catalytic) and
      beta (transport) subunits, as quantified by immunoblots of the reaction products
      for nitrotyrosine. To evaluate for peroxynitrite damage to Na,K-ATPase in vivo,
      striatal plasma membrane fractions from 1-week-old piglets subjected to asphyxic
      cardiac arrest and recovery were also studied by immunoprecipitation. During the
      progression of striatal neurodegeneration and loss of enzyme function 3-24 h
      after arrest, nitration of the alpha3 (neuronal) isoform of Na,K-ATPase was not
      increased relative to sham control. Suprisingly, however, nitration of this alpha
      isoform occurs during normal brain development and peaks at 2 weeks of age. We
      conclude that Na,K-ATPase is a target of peroxynitrite, but that this mechanism
      is not responsible for enzyme inactivation after HI. Protein nitration may serve
      as marker of other normal, noninjurious cell processes in the developing brain.

PMID- 14649732
TI  - High levels of orexin A in the brain of the mouse model for phenylketonuria:
      possible role of orexin A in hyperactivity seen in children with PKU.
AB  - Phenylketonuria (PKU) is a metabolic disorder caused by phenylalanine hydroxylase
      deficiency leading to increased levels of phenylalanine in the brain.
      Hyperactivity is reportedly induced by a high level of orexin A, and therefore
      orexin A content was studied in the PKU mice. Hypothalamus and brain stem had
      higher levels of orexin A compared to cerebrum and cerebellum both in wild type
      and PKU mice brains as observed by radioimmunoassay method. Interestingly, all
      these regions of the brain in PKU mouse showed a higher level of orexin A
      compared to the wild type. Heart and plasma also had higher levels of orexin A in
      PKU compared to the wild type. Immunohistochemical analysis revealed an increased
      number of orexin A-stained cells in the brain and heart of PKU mouse compared to
      the wild type. This is the first report of increased level of orexin in the PKU
      mouse brain. Hyperactivity is commonly observed in children with PKU; thus these
      findings suggest that orexin A is a contributing factor for the hyperactivity.

PMID- 14649733
TI  - Antioxidant ability and lipid peroxidation in the hippocampus with
      epileptogenesis induced by Fe3+ injection into the amygdaloid body of rats.
AB  - To analyze antioxidant ability and lipid peroxidation in the hippocampus of rats
      in an interictal state of FeCl3-induced epileptogenesis, the hippocampal
      eliminating decay ratio of exogenously applied nitroxide radical (3-carbamoyl
      2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL)) by electron
      paramagnetic resonance (EPR) spectroscopy, and the thiobarbituric reactive
      substances (TBARS) level in the hippocampus were measured. The prolonged half
      life of electron paramagnetism of carbamoyl-PROXYL in the hippocampus of rats
      with chronic FeCl3-induced epileptogenesis revealed decreased antioxidant
      ability, which supports the vulnerability against oxidative stress. In addition,
      TBARS level (marker of lipid peroxidation) was increased in the hippocampus of
      rats injected with FeCl3 compared with that of control. This study revealed that
      repetitive seizures resulted in the decreased hippocampal antioxidant ability
      with lipid peroxidation and explained the regional vulnerability to oxidative
      stress in the limbic system with epileptogenesis.

PMID- 14649734
TI  - Comparison of treatments for pelvic congestion syndrome.
AB  - To evaluate the efficacy of various treatments for pelvic congestion syndrome in
      patients with different stress levels, we analyzed one hundred six patients with
      pelvic congestion syndrome, confirmed with laparoscopy and venography, who did
      not respond to medication after 4-6 months medication. They were divided into
      three groups: (embolotherapy; hysterectomy with bilateral oophorectomy and
      hormone replacement therapy; and hysterectomy with unilateral oophorectomy). The
      visual analog scale was used to measure degree of pain; stress level data were
      scored with the revised social readjustment rating scale. Embolotherapy was
      significantly more effective at reducing pelvic pain, compared to the other
      methods (p < 0.05). The mean percentage decrease in pain was significantly
      greater in the patients with lower stress scores (p < 0.05). Ovarian and/or
      internal iliac vein embolization appears to be a safe, well-tolerated, effective
      treatment for pelvic congestion syndrome that has not responded to medication.

PMID- 14649735
TI  - Firearm-related mortality: a review of four hundred-forty four deaths in
      Diyarbakir, Turkey between 1996 and 2001.
AB  - The current study is based on a retrospective investigation of firearm deaths in
      Diyarbakir, which were autopsied by the Diyarbakir Branch of the Council of
      Forensic Medicine during the 6- year period. Four hundred-forty four deaths were
      investigated from January 1996 through December 2001, including homicide (296
      cases, 66.7%), suicide (120 cases, 27%) and accidental shootings (28 cases,
      6.3%). The age range of all firearm deaths in the study period was 5 to 75 years
      with a median age of 29.8 years. The majority were in the groups aged 16-25 years
      (38.7%). In the homicide group, 248 subjects (83.8%) were male, and 48 (16.2%)
      were female. The 31.1% of the homicide victims were in the group aged at 20-30
      years. Of the 120 suicide victims, 56 (46.7%) were in the group aged 16-20 years.
      The head was by far the favoured site, accounting for 82 (68.3%) deaths: entry
      wounds in the right temple accounted for 72 of these. Twenty-eight cases were
      accidental shootings and 18 of them were male (64.3%). Twelve of the 28
      accidental victims (42.9%) were in the group aged 0-10 years. The eight cases
      were due to their own accidental shootings, and the remaining 20 cases were shot
      by others. Our findings show that the contributing factors for increasing death
      by firearm are terrorists' activities, traditional habits of obtaining and using
      guns and blood feuds.

PMID- 14649736
TI  - Thiols, malonaldehyde and total antioxidant status in the Turkish patients with
      type 2 diabetes mellitus.
AB  - Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) is a risk factor for
      cardiovascular diseases (CVD). Oxidative stress mechanisms are often reported to
      be implied in type 2 diabetes mellitus. In order to determine their clinical
      relevance, we investigated several plasma indicators in the Turkish patients with
      NIDDM: (i) homocysteine (Hcy) and cysteine (Cys) which contribute to increase the
      risk of atherosclerosis during NIDDM, (ii) glutathione (GSH) and cysteinylglycine
      (CysGly) resulting from GSH degradation catalyzed by gamma-glutamylcysteine
      transferase (GGT), (iii) malonaldehyde (MDA) as a marker for lipid peroxidation,
      and (iv) total antioxidant status (TAS). Our main results were evaluated based on
      sex and diabetic status. In female patients, plasma concentrations of MDA and Hcy
      were significantly higher than in controls, while GSH levels were significantly
      lower. In males, a difference between control and diabetic groups was noticed
      only for Hcy, levels being also higher in patients. In the diabetic group,
      increase in serum glucose concentration was significantly correlated with
      increased GGT activity. In both controls and diabetic patients, GGT activity was
      correlated with a raised Cys concentration and a decreased GSH level. In both
      controls and diabetic patients, there were significant positive correlations
      between Cys and Hcy and between GSH and Hcy. We concluded that GSH and MDA levels
      are clinical indicators for an oxidative process linked to type 2 diabetes
      mellitus, especially in women.

PMID- 14649737
TI  - Efficacy of amikacin combinations for nocardiosis.
AB  - We isolated five bacterial strains from patients diagnosed as having nocardiosis.
      Bacterial species were identified based on the similarities in the nucleotide
      sequences of 16S ribosomal RNAs. Three of the five strains were identified as
      Nocardia asteroids, but unexpectedly other two were Streptomyces hygroscopicus
      and Rothia dentocariosa. The latter two species are not members of the family
      Nocardiaceae. We investigated the susceptibilities of these five strains to the
      following nine antimicrobial agents: trimethoprim/sulfamethoxazole (TMP/SMX),
      minocycline (MINO), erythromycin (EM), amikacin (AMK), cefotaxime (CTX),
      faropenem (FRPM), imipenem (IPM), ciprofloxacin (CPFX), and sparfloxacin (SPFX).
      The minimum inhibitory concentration (MIC) ranges (mg/ml) were as follows: TMP
      SMX, 4- > 32; MINO, 0.125-8; EM, < or = 0.016- > 32; AMK, 1-2; CTX, 0.063- > 32;
      FRPM, 0.063-16; IPM, 0.125-2; CPFX, 4-32; and SPFX, 0.5-16. Moreover, the
      synergistic effects of AMK in combination with each of TMP-SMX, MINO, EM, CTX,
      IPM, and SPFX were investigated by checkerboard synergy testing. No antagonism
      was recognized for the three N. asteroides strains. Synergistic and additive
      effects were observed for the combinations of AMK with CTX, IPM, or SPFX.

PMID- 14649738
TI  - Influence of acute exercise on urinary protein, creatinine, insulin-like growth
      factor-I (IGF-I) and IGF binding protein-3 concentrations in children.
AB  - Insulin-like growth factor-I (IGF-I) is a polypeptide hormone and present in
      human urine. Insulin-like growth factor binding protein-3 (IGFBP-3) is the major
      form of binding protein in human circulation and functions as a carrier for IGF
      I. Our goal was to determine the effects of volleyball exercise on the
      concentrations of urine protein, creatinine, IGF-I, and IGFBP-3 in children and
      to find out whether these effects differ between boys and girls. Volunteer
      children (13 females and 14 males), aged 10-13 years old were included in this
      work. Weight and height of the subjects were measured, and urine samples of their
      were collected before and after 2 hours of exercise. Urinary protein, creatinine,
      IGF-I and IGFBP-3 levels were analysed. Urinary protein, creatinine and IGF-I
      concentrations were increased after two hours of exercise wheres urinary IGFBP-3
      concentrations did not change. In addition, no statistically significant
      difference in all parameters analysed was observed between boys and girls of
      similar age and body mass index.

PMID- 14649739
TI  - Oral health of patients with Parkinson's disease: factors related to their better
      dental status.
AB  - Contrary to intuitive preconceptions, patients with Parkinson's disease (PD) have
      been reported to have less carious teeth. The present study was undertaken to
      seek responsible factors for this unexpected finding. The PD patients consisted
      of 31 consecutive university hospital outpatients who were 60 years old or over,
      and the controls of 104 comparable outpatients at a dental clinic. They were
      inspected for their dental status, and interviewed on their toothbrushing habits
      and dietary preferences. Their unstimulated saliva samples were collected and
      their flow volume and pH were measured. The total numbers of carious teeth (DMFT:
      Decayed, Missing, and Filled Teeth) and other related variables were compared
      between the two groups by stratification. In total, the DMFT for the PD patients
      was significantly fewer than for the control. The salivary flow and pH were
      correlated to the DMFT, but the difference between the two groups was not
      significant. Frequency of toothbrushing was higher among the PD patients. The
      lower DMFT among the patients became insignificant when salivary pH was 6 or
      less, toothbrushing was 2 times a day or less, or the response was positive to
      the question on the habit of eating snacks between regular meals. In summary, the
      oral health of PD outpatients with mild symptoms was better than the controls.
      However, in cases with poor oral hygiene status, the PD patient's oral health was
      not different from the control. This suggests that they are not invariably
      protected from caries-associated factors. The generic property of PD may not
      fully explain the apparent difference in DMFT.

PMID- 14649740
TI  - Can nasal continuous positive airway pressure decrease clinic blood pressure in
      patients with obstructive sleep apnea?
AB  - Obstructive sleep apnea (OSA) is commonly associated with systemic hypertension
      and now recognized as an independent risk factor for daytime hypertension. We
      aimed to study the short- and long-term effect of nasal continuous positive
      airway pressure (CPAP) in hypertensive and normotensive patients with OSA. Forty
      six patients with moderated to severe OSA were treated with nasal CPAP and
      followed after one year of treatment. Clinic blood pressure, heart rate, and body
      weight were taken before and followed up for one year after beginning nasal CPAP.
      In this study 25 patients with OSA were found to have hypertension (54.3%). The
      hypertensive group showed a significant reduction in clinic blood pressure after
      nasal CPAP, whereas the normotensive group showed no changes. The subgroup of
      hypertensive patients with OSA who had no anti-hypertensive medication revealed a
      decrease in clinic blood pressure comparable to those with anti-hypertensive
      drugs. The heart rate was not significantly changed in any patients. There was no
      significant correlation between the decrease in body weight and the reduction in
      blood pressure. These results suggest that nasal CPAP alone might have a
      substantial blood pressure lowering effect in hypertensive patients with OSA.
      This effect could decrease the morbidity and mortality related to cardiovascular
      complications in patients with OSA.

PMID- 14649741
TI  - Prevention of liquid-diet-induced damages on submandibular glands by selenium
      supplementation in rats.
AB  - This study was designed to explore the protective effects of selenium on
      submandibular glands of rats that were maintained on liquid diet. The animals
      kept on liquid diet for 10 days following 20 days of solid diet, had severe
      degeneration on both acinar and ductal cells: pycnotic nuclei, enlarged granular
      endoplasmic reticulum, swollen mitochondria with separated cristae, reduction of
      secretory granules and abundant lipid droplets were observed. Body and gland
      weights of these animals were found to decrease significantly compared to those
      of control group given solid diet for 30 days. The animals that were fed 20 days
      with solid diet + 10 days liquid diet and also given selenium 0.4 mg/kg for 30
      days, did not have any remarkable sign of degeneration on submandibular glands,
      and their gland weights significantly increased when compared to the animals fed
      with liquid diet without selenium supplementation. Submandibular glands of the
      group that was maintained on solid diet for 30 days and supplemented with
      selenium in drinking water were found to be normal. They showed consistent gain
      in both body and gland weights almost equal to that of control group. As a
      result, we assume that adding selenium in liquid diet can prevent the detrimental
      effects of liquid diet consumption on submandibular glands.

PMID- 14649742
TI  - Image processing and analysis at IPAG.

PMID- 14649743
TI  - Tracking the optic nervehead in OCT video using dual eigenspaces and an adaptive
      vascular distribution model.
AB  - Optical coherence tomography (OCT) is a new ophthalmic imaging modality
      generating cross sectional views of the retina. OCT systems are essentially
      Michelson interferometers that form images in 1.5 s by directing a
      superluminescent diode (SLD) beam over the retinal surface. Involuntary eye
      motions frequently cause incorrect locations to be imaged. This motion may leave
      no obvious artifacts in the scan data and can easily go undetected. For glaucoma
      monitoring especially, knowing the measurement path, typically a circle
      concentric with the nerve head, is crucial. The commercially available OCT system
      displays a near-infrared video of the retina showing the SLD beam. This paper
      presents a prototype system to detect the nerve head and SLD beam in the video,
      and report the true scan path relative to the nerve head. Low image contrast and
      limited resolution make the reliable detection of retinal features difficult. In
      an adaptive model construction phase, the system directly detects retinal
      vasculature and the nerve head and incrementally builds a model of the current
      subject's vascular pattern relative to the optic disk. The nerve head
      identification is multitiered, using a novel dual eigenspace technique and a
      geometric comparison of detected vessel positions and nerve head hypotheses. In
      its operational phase, a correspondence is achieved between the currently
      detected vasculature and the model. Using subjects not included in training, the
      system located the optic nerve head to within 5 pixels (0.07 optic disk
      diameters, an error well below clinical significance) in 99.75% of 2800 video
      fields. In current clinical practice, motions as large as 1-2 disc diameters may
      go undetected, so this is a vast improvement.

PMID- 14649744
TI  - Extraction of periodic multivariate signals: mapping of voltage-dependent dye
      fluorescence in the mouse heart.
AB  - In many experimental circumstances, heart dynamics are, to a good approximation,
      periodic. For this reason, it makes sense to use high-resolution methods in the
      frequency domain to visualize the spectrum of imaging data of the heart and to
      estimate the deterministic signal content and extract the periodic signal from
      background noise in experimental data. In this paper, we describe the first
      application of a new method that we call cardiac rhythm analysis which uses a
      combination of principal component analysis and multitaper harmonic analysis to
      extract periodic, deterministic signals from high-resolution imaging data of
      cardiac electrical activity, We show that this method significantly increases the
      signal-to-noise ratio of our recordings, allowing for better visualization of
      signal dynamics and more accurate quantification of the properties of electrical
      conduction. We visualize the spectra of three cardiac data sets of mouse hearts
      exhibiting sinus rhythm, paced rhythm and monomorphic tachycardia. Then, for
      pedagogical purposes, we investigate the tachycardia more closely, demonstrating
      the presence of two distinct periodicities in the re-entrant tachycardia.
      Analysis of the tachycardia shows that cardiac rhythm analysis not only allows
      for better visualization of electrical activity, but also provides new
      opportunities to study multiple periodicities in signal dynamics.

PMID- 14649745
TI  - Induced-current electrical impedance tomography: a 2-D theoretical simulation.
AB  - A reconstruction algorithm, based on the modified Newton-Raphson algorithm, was
      developed for induced-current electrical impedance tomography and studied in
      theoretical two-dimensional geometry representing a human thorax. The finite
      volume method was applied for the discretization of the physical domain,
      resulting in a symbolic representation of the Jacobian matrix, which is accurate
      and fast to construct. Several system configurations, differing in the number of
      excitation coils and electrodes, were simulated, and the performance in thoracic
      imaging was studied. It was found that a six-coil system shows a significant 40%
      improvement of conductivity values reconstruction over the three-coil system (an
      error of 2.06 omega(-1) compared with 3.44 omega(-1)). A number of 32 electrodes
      was found to be sufficient, being the smallest number of electrodes to still
      provide a reasonable performance (only 4.2% degradation in average conductivity
      error compared with the maximum possible 106-electrode system).

PMID- 14649746
TI  - A robust method for registration of three-dimensional knee implant models to two
      dimensional fluoroscopy images.
AB  - A method was developed for registering three-dimensional knee implant models to
      single plane X-ray fluoroscopy images. We use a direct image-to-image similarity
      measure, taking advantage of the speed of modern computer graphics workstations
      to quickly render simulated (predicted) images. As a result, the method does not
      require an accurate segmentation of the implant silhouette in the image (which
      can be prone to errors). A robust optimization algorithm (simulated annealing) is
      used that can escape local minima and find the global minimum (true solution).
      Although we focus on the analysis of total knee arthroplasty (TKA) in this paper,
      the method can be (and has been) applied to other implanted joints, including,
      but not limited to, hips, ankles, and temporomandibular joints. Convergence tests
      on an in vivo image show that the registration method can reliably find poses
      that are very close to the optimal (i.e., within 0.4 degrees and 0.1 mm), even
      from starting poses with large initial errors. However, the precision of
      translation measurement in the Z (out-of-plane) direction is not as good. We also
      show that the method is robust with respect to image noise and occlusions.
      However, a small amount of user supervision and intervention is necessary to
      detect cases when the optimization algorithm falls into a local minimum.
      Intervention is required less than 5% of the time when the initial starting pose
      is reasonably close to the correct answer, but up to 50% of the time when the
      initial starting pose is far away. Finally, extensive evaluations were performed
      on cadaver images to determine accuracy of relative pose measurement. Comparing
      against data derived from an optical sensor as a "gold standard," the overall
      root-mean-square error of the registration method was approximately 1.5 degrees
      and 0.65 mm (although Z translation error was higher). However, uncertainty in
      the optical sensor data may account for a large part of the observed error.

PMID- 14649747
TI  - Data analysis protocols for assessing improvement in visibility under the U.S.
      Environmental Protection Agency (EPA) regional haze rule.

PMID- 14649749
TI  - Thermal exploitation of wastes with lignite for energy production.
AB  - The thermal exploitation of wastewood with Greek lignite was investigated by
      performing tests in a laboratory-scale fluidized bed reactor, a 1-MW(th) semi
      industrial circulating fluidized bed combustor, and an industrial boiler. Blends
      of natural wood, demolition wood, railroad sleepers, medium-density fiberboard
      residues, and power poles with lignite were used, and the co-combustion
      efficiency and the effect of wastewood addition on the emitted pollutants were
      investigated. Carbon monoxide, sulfur dioxide, and oxides of nitrogen emissions
      were continuously monitored, and, during the industrial-scale tests, the toxic
      emissions (polychlorinated dibenzodioxins and dibenzofurans and heavy metals)
      were determined. Ash samples were analyzed for heavy metals in an inductively
      coupled plasma-atomic emission spectroscopy spectrophotometer. Problems were
      observed during the preparation of wastewood, because species embedded with
      different compounds, such as railway sleepers and demolition wood, were not
      easily treated. All wastewood blends were proven good fuels; co-combustion
      proceeded smoothly and homogeneous temperature and pressure profiles were
      obtained. Although some fluctuations were observed, low emissions of gaseous
      pollutants were obtained for all fuel blends. The metal element emissions (in the
      flue gases and the solid residues) were lower than the legislative limits.
      Therefore, wastewood co-combustion with lignite can be realized, provided that
      the fuel handling and preparation can be practically performed in large-scale
      installations.

PMID- 14649748
TI  - An air quality data analysis system for interrelating effects, standards, and
      needed source reductions.

PMID- 14649750
TI  - Sources and concentrations of indoor nitrogen dioxide in Barcelona, Spain.
AB  - Sources and concentrations of indoor nitrogen dioxide (NO2) were examined in
      Barcelona, Spain, during 1996-1999. A total of 340 dwellings of infants
      participating in a hospital-based cohort study were selected from different areas
      of the city. Passive filter badges were used for indoor NO2 measurement over 7-30
      days. Dwelling inhabitants completed a questionnaire on housing characteristics
      and smoking habits. Data on outdoor NO2 concentrations were available for the
      entire period of the study in the areas of the city where indoor concentrations
      were determined. Bivariate analysis was performed to investigate relationships
      between indoor NO2 concentrations on one hand and outdoor NO2 concentrations,
      housing, and occupant characteristics on the other. Stepwise multiple linear
      regression was performed with variables that were found to have a significant
      bivariate relationship. Indoor NO2 mean values ranged between 23.57 ppb in 1996
      and 27.02 ppb in 1999, with the highest yearly value of 27.82 ppb in 1997. In the
      same time period, mean outdoor NO2 concentration ranged between 25.26 and 25.78
      ppb with a peak of 30.5 ppb in 1998. Multiple regression analysis showed that
      principal sources of indoor NO2 concentrations were the use of a gas cooker, the
      absence of an extractor fan when cooking, and cigarette smoking. The absence of
      central heating was also associated with higher NO2 concentrations. Finally, each
      ppb increase in outdoor NO2 was associated with a 1% increase in indoor
      concentrations.

PMID- 14649751
TI  - A new method to assess mercury emissions: a study of three coal-fired electric
      generating power station configurations.
AB  - U.S. Environmental Protection Agency (EPA) Method 7473 for the analysis of
      mercury (Hg) by thermal decomposition, amalgamation, and atomic absorption
      spectroscopy has proved successful for use in Hg assessment at coal-fired power
      stations. In an analysis time of approximately 5 min per sample, this
      instrumental methodology can directly analyze total Hg--with no discrete sample
      preparation--in the solid matrices associated with a coal-fired power plant,
      including coal, fly ash, bottom ash, and flue gas desulfurization (FGD) material.
      This analysis technique was used to investigate Hg capture by coal combustion
      byproducts (CCBs) in three different coal-fired power plant configurations. Hg
      capture and associated emissions were estimated by partial mass balance. The
      station equipped with an FGD system demonstrated 68% capture on FGD material and
      an emissions estimate of 18% (11 kg/yr) of total Hg input. The power plant
      equipped with low oxides of nitrogen burners and an electrostatic precipitator
      (ESP) retained 43% on the fly ash and emitted 57% (51 kg/yr). The station
      equipped with conventional burners and an ESP retained less than 1% on the fly
      ash, emitting an estimated 99% (88 kg/yr) of Hg. Estimated Hg emissions
      demonstrate good agreement with EPA data for the power stations investigated.

PMID- 14649752
TI  - An air quality data analysis system for interrelating effects, standards, and
      needed source reductions: Part 13--Applying the EPA Proposed Guidelines for
      Carcinogen Risk Assessment to a set of asbestos lung cancer mortality data.
AB  - The Clean Air Act Amendments of 1990 (CAAA-90) list 189 hazardous air pollutants
      (HAPs) for which "safe" ambient concentrations are to be determined. The primary
      purpose of this paper is to develop two mathematical models, lognormal and
      logarithmic, that effectively express excess lung cancer mortality as a function
      of asbestos concentration for an example set of data and also to suggest using
      these two models for additional HAPs. The secondary purpose of this paper is to
      calculate a "safe" asbestos concentration by first assuming a default linear
      extrapolation (to one excess death per million people, as specified for
      carcinogenic HAPs). The resulting "safe" concentration is an impossible-to
      achieve 1/1000 of present background asbestos concentrations. A letter to the
      editor and a response in this Journal issue use additional asbestos data that
      suggest that the "safe" concentration should be about 730 times higher than first
      calculated here and that a default nonlinear extrapolation should be used
      instead, with the "safe" concentration proportional to the desired mortality
      level raised to the 0.39 power. These results suggest that the most important
      problem in setting a "safe" concentration for each carcinogenic HAP is to
      determine the correct nonlinear extrapolation to use for each HAP.

PMID- 14649753
TI  - Latent hydraulic reactivity of blended cement incorporating slag made from
      municipal solid waste incinerator fly ash.
AB  - The reactivity of cement pastes made by blending Portland cement with slag from
      municipal solid waste incinerator (MSWI) fly ash was investigated to assess the
      potential of recycling MSWI fly ash slag. The slag, prepared by melting MSWI fly
      ash at 1400 degrees C for 30 min, was pulverized and ground, then blended with
      ordinary Portland cement (OPC), using various substitution levels to make slag
      blended cement (SBC). The pozzolanic reactivity of the ecocement was then
      characterized by determining variations in the compressive strength, degree of
      hydration, microstructure, speciation, and mineralogical crystalline phases. The
      results suggest that the strength of the pastes at an early age decreased with
      increasing substitution levels, whereas the strength at a later age of the tested
      pastes (with substitution levels less than 10%) outperformed OPC paste because of
      typical SBC properties. The development of strength at a later age was also
      confirmed by X-ray diffraction and scanning electron microscopy techniques. This
      implies that active silica (Si) and alumina (Al) react with the hydration
      product, calcium hydroxide (Ca(OH)2), to form calcium silicate hydrate (C-S-H),
      which contributed to strength development at a later age by the filling up of
      pores in the SBC pastes. The pozzolanic activity of the SBC pastes indicates that
      it is suitable for use as a substitute for OPC in blended cement.

PMID- 14649754
TI  - Potential for reducing indoor styrene exposure from copied paper through use of
      low-emitting toners.
AB  - Tests were conducted using 53-L dynamic chambers to determine airborne styrene
      emission rates over time from freshly copied paper. Copies were produced on a
      single photocopier using two toners manufactured for this copier but having
      different styrene contents. The resulting emission models were used to predict
      whether indoor styrene concentrations resulting from copied paper in a typical
      office might be significantly reduced by use of a low-emitting toner for a given
      copier. The styrene emissions were best represented by either a 3rd-order decay
      model or by a power law model having an exponent between 0.3 and 0.5 (R2 = 0.94
      0.99). The two toners resulted in copied paper having significantly different
      styrene emissions (p < 0.01), with unit mass emissions over 1000 hr being nine
      times greater with the higher-emitting toner. But copied paper is predicted to
      produce peak indoor styrene concentrations in a typical office no more than 1% of
      the World Health Organization health-based guideline. Thus, for the toners
      considered here, indoor styrene exposures from copied paper appear to be too
      limited to provide incentive for switching to the lower-emitting toner. The
      ability to generalize these conclusions is limited by the fact that only one
      copier and two toners could be tested.

PMID- 14649755
TI  - Impact of unleaded gasoline introduction on the concentration of lead in the air
      of Dhaka, Bangladesh.
AB  - Airborne particulate matter (APM) samples collected at a semiresidential area in
      Dhaka, Bangladesh, during the periods of 1994 and 1997-2000 have been studied to
      assess the impact of the use of unleaded gasoline in Bangladesh. According to
      scanning electron microscopy/ energy-dispersive X-ray microanalyzer studies, lead
      (Pb) was found as Pb sulfates and Pb halides in motor-vehicle exhaust particles,
      whose diameters were some hundreds of nanometers. No significant changes in the
      annual averages of APM mass and black carbon concentrations have been observed
      over the period. The yearly average Pb concentration reached a maximum value of
      370 ng/m3 in the particulate matter with an aerodynamic diameter < 2.5 microm
      fraction in 1998. In 2000, the concentration decreased to approximately one-third
      (106 ng/m3) of the high earlier values after the introduction of unleaded
      gasoline in 1999. A significant lowering of the blood Pb level of the population
      over next few years is expected as a result of this great decrease in Pb
      concentration.

PMID- 14649756
TI  - Strength development of solidified/stabilized organic waste and optimum treatment
      design.
AB  - Artificially contaminated (spiked) natural soils were solidified/stabilized using
      various combinations of commonly used additives, such as lime, cement, fly ash,
      activated carbon, and silica fume. The effectiveness of the
      solidification/stabilization (S/S) processes was evaluated based on experimental
      findings from compaction testing, unconfined compressive shear strength, and X
      ray diffraction (XRD). Correlations of limited reliability between unconfined
      compressive strength and penetrometer and torvane measurements were derived.
      Results from XRD experiments indicated that certain organic contaminants (i.e.,
      naphthalene and pyrene) might impact the S/S processes for a given combination of
      additives. The type and amount of organic contaminants also affected the
      pozzolanic reactions. Specifically, the absence or small peak intensity of
      pozzolanic product XRD patterns for a given combination of additives was a good
      indication that the type and the amount of organic contaminant present inhibited
      pozzolanic reactions. This phenomenon was tested and confirmed for actual field
      contaminated samples.

PMID- 14649757
TI  - Biofiltration of cyclic air emissions of alpha-pinene at low and high
      frequencies.
AB  - Biofiltration of periodically fluctuating concentrations of an alpha-pinene-laden
      waste gas was investigated to treat both high-frequency and low-frequency
      fluctuations. The effects of periodic concentration fluctuations on biofilter
      performance were measured. Controlled variables of periodic operation included
      cycle period and amplitude. The cycle period ranged from 10 min to 6 days, with
      the inlet alpha-pinene concentration fluctuating between 0 and 100 parts per
      million volume. At high-frequency concentration cycling (i.e., on the order of
      minutes), both cyclic and constant concentration biofilters maintained similar
      long-term performance with an average removal efficiency of 77% at an averaged
      loading rate of 29 g alpha-pinene/m3 bed/hr. A first approximation suggests
      kinetics that are time-independent, indicating that steady-state data can be used
      to predict transient behavior at this time scale. Cyclic biofilter operation with
      a cycle period of 24 hr (with equal on/off time) was achievable for biofilters
      without a significant loss in performance. At longer time scales, cyclic
      biofilter performance decreased at the restart of the ON cycle. The recovery time
      to previous levels of performance increased with increasing cycle period; the
      recovery time was less than 1 hr for a cycle period of 24 hr and between 6 and 8
      hr for a cycle period of 6 days.

PMID- 14649758
TI  - Adsorption and desorption characteristics of semiconductor volatile organic
      compounds on the thermal swing honeycomb zeolite concentrator.
AB  - The use of a honeycomb zeolite concentrator and an oxidation process is one of
      the most popular methods demonstrated to control volatile organic compound (VOCs)
      emissions from waste gases in semiconductor manufacturing plants. This study
      attempts to characterize the performance of a concentrator in terms of the
      removal efficiencies of semiconductor VOCs (isopropyl alcohol [IPA], acetone,
      propylene glycol methyl ether [PGME], and propylene glycol monomethyl ether
      acetate [PGMEA]) under several parameters that govern the actual operations.
      Experimental results indicated that at inlet temperatures of under 40 degrees C
      and a relative humidity of under 80%, the removal efficiency of a zeolite
      concentrator can be maintained well over 90%. The optimal rotation speed of the
      concentrator is between 3 and 4.5 rph in this study. The optimal rotation speed
      increases with the VOCs inlet concentration. Furthermore, reducing the
      concentration ratio helps to increase the removal efficiency, but it also
      increases the incineration cost. With reference to competitive adsorption, PGMEA
      and PGME are more easily adsorbed on a zeolite concentrator than are IPA and
      acetone because of their high boiling points and molecular weights.

PMID- 14649759
TI  - Partitioning gas tracer tests for measurement of water in municipal solid waste.
AB  - A key component in the operation of almost all bioreactor landfills is the
      addition of water to maintain optimal moisture conditions. To determine how much
      water is needed and where to add it, in situ methods are required to measure
      water within solid waste. Existing technologies often result in measurements of
      unknown accuracy, because of the variability of solid waste materials and time
      dependent changes in packing density, both of which influence most measurement
      methods. To overcome these problems, a new technology recently developed by
      hydrologists for measuring water in the vadose zone--the partitioning gas tracer
      test--was tested. In this technology, the transport behavior of two gas tracers
      within solid waste is used to measure the fraction of the void space filled with
      water. One tracer is conservative and does not react with solids or liquids,
      while a second tracer partitions into the water and is separated from the
      conservative tracer during transport. This technology was tested in four
      different solid waste packings and was capable of determining the volumetric
      water content to within 48% of actual values, with most measurement errors less
      than 15%. This technology and the factors that affect its applicability to
      landfills are discussed in this paper.

PMID- 14649760
TI  - Quantification of hourly variability in NO(x) emissions for baseload coal-fired
      power plants.
AB  - The objectives of this paper are to (1) quantify variability in hourly utility
      oxides of nitrogen (NO(x)) emission factors, activity factors, and total
      emissions; (2) investigate the autocorrelation structure and evaluate cyclic
      effects at short and long scales of the time series of total hourly emissions;
      (3) compare emissions for the ozone (O3) season versus the entire year to
      identify seasonal differences, if any; and (4) evaluate interannual variability.
      Continuous emissions monitoring data were analyzed for 1995 and 1998 for 32 units
      from nine baseload power plants in the Charlotte, NC, airshed. Unit emissions
      have a strong 24-hr cycle attributable primarily to the capacity factor. Typical
      ranges of the coefficient of variation for emissions at a given hour of the day
      were from 0.2 to 0.45. Little difference was found when comparing weekend
      emissions with the entire week or when comparing the O3 season with the entire
      year. There were substantial differences in the mean and standard deviation of
      emissions when comparing 1995 and 1998 data, indicative of the effect of
      retrofits of control technology during the intervening time. The wide range of
      variability and its autocorrelation should be accounted for when developing
      probabilistic utility emission inventories for analysis of near-term future
      episodes.

PMID- 14649761
TI  - Effect of SiO2 on immobilization of metals and encapsulation of a glass network
      in slag.
AB  - The final disposal of ash from an incinerator is of special concern because of
      the possibility of its releasing toxic substances. Melting/vitrification has been
      regarded as a prospective technology of ash treatment. The object of this
      investigation was to evaluate the effect of silica (SiO2) addition on the
      immobilization of hazardous metals and the encapsulation of a glass network
      during the vitrification process. Four specimens with SiO2/fly ash mixing ratios
      of 0, 0.1, 0.2, and 0.3, respectively, were tested. The mobility of metals in
      slag was then estimated by a sequential extraction procedure. X-ray diffraction
      analysis indicates that SiO2 leads to the polymerization of silicates. The
      encapsulation of aluminum, calcium, and magnesium would not be observed unless
      adequate amount of SiO2 was added. It was also found that SiO2 addition enhances
      the formation of a compact and interconnected glass network structure and, thus,
      contributes to the chemical stability of metals in slag. After vitrification, the
      mobility of cadmium, copper, iron, chromium, nickel, lead, and zinc was
      significantly reduced. However, there is no significant correlation between the
      immobilization of these metals and the addition of SiO2.

PMID- 14649762
TI  - Tuberculin skin test conversion among healthcare workers after exposure to a
      patient with pleural effusion and parenchymal disease unapparent on chest X-ray.

PMID- 14649763
TI  - Varicella seroprevalence among Turkish medical students and the validity of
      disease history.

PMID- 14649764
TI  - How good is the tuberculin skin test?

PMID- 14649765
TI  - First do no harm: ensuring that healthcare workers vaccinate and are vaccinated.

PMID- 14649766
TI  - A survey of latent tuberculosis infection among laboratory healthcare workers in
      New York City.
AB  - OBJECTIVE: To determine the prevalence of positive tuberculin skin tests (TSTs),
      incidence of TST conversion, risk factors for positive TSTs, and history of
      active TB among HCWs in microbiology laboratories in New York City. DESIGN: Two
      year survey from May 1999 to June 2001. SETTING: Nineteen microbiology
      laboratories. RESULTS: During the first year, interviews were conducted with 345
      laboratory HCWs (mean, 18 HCWs per site; range, 2 to 51) to assess the prevalence
      of positive TSTs, but 3 (1%) could not recall their result and were excluded from
      further analyses. The mean age of the remaining 342 HCWs was 48 years; 68% (n =
      233) were female, 54% (n = 183) received bacille Calmette-Guerin (BCG)
      vaccination, and 71% (n = 244) were foreign born. The prevalence of a positive
      TST was 57% (n = 196), but only 20% (n = 39) of the HCWs received isoniazid. The
      incidence of TST conversion in the second year of the study was 1% (1 of 108).
      Multivariate analysis identified age (odds ratio [OR] per year, 1.05; 95%
      confidence interval [CI95], 1.02-1.08), foreign birth (OR, 3.80; CI95, 1.98
      7.28), BCG immunization (OR, 4.89; CI95, 2.72-8.80), and employment in a
      mycobacteriology laboratory (OR, 2.14; CI95, 1.25-3.68) as risk factors for a
      positive TST. Only one HCW had been treated for active TB. CONCLUSIONS: The
      prevalence of positive TSTs was high among laboratory HCWs, but the TST
      conversion rate was low. Higher rates of treatment for latent TB infection are
      desirable.

PMID- 14649767
TI  - Prevalence of tuberculin skin test positivity and conversions among healthcare
      workers in New York City during 1994 to 2001.
AB  - OBJECTIVE: To determine the prevalence of and risk factors for tuberculin skin
      test positivity and conversion among New York City Department of Health and
      Mental Hygiene employees. DESIGN: Point-prevalence survey and prospective cohort
      analysis. Sentinel surveillance was conducted from March 1, 1994, to December 31,
      2001. PARTICIPANTS: HCWs in high-risk and low-risk settings for occupational TB
      exposure. RESULTS: Baseline tuberculin positivity was 36.2% (600 of 1,658), 15.5%
      (143 of 922) among HCWs born in the United States, and 48.5% (182 of 375) among
      HCWs not born in the United States. There were 36 tuberculin conversions during
      2,754 observation-years (rate, 1.3 per 100 person-years). For HCWs born in the
      United States, the risk for tuberculin conversion was greater in high-risk
      occupational settings compared with low-risk settings (OR, 5.7; CI95, 1.7-19.2; P
      < .01). HCWs not born in the United States and those employed at the Office of
      the Chief Medical Examiner (OCME) were at high risk for baseline tuberculin
      positivity (OR, 3.2; CI95, 1.7-5.8; P < .001); OCME HCWs (OR, 4.7; CI95, 2.3-9.4;
      P < .001), those of Asian ethnicity (OR, 4.3; CI95, 1.4-13.5; P < .01), and older
      HCWs (OR, 1.0; CI95, 1.0-1.1; P < .05) were at a higher risk for conversion.
      CONCLUSIONS: Although the prevalence of tuberculin positivity decreased after the
      peak of the recent TB epidemic in New York City, the conversion rate among HCWs
      in high-risk occupational settings for TB exposure was still greater than that
      among HCWs in low-risk settings. Continued surveillance of occupational TB
      infection is needed, especially among high-risk HCWs.

PMID- 14649768
TI  - Costs of implementing and maintaining a tuberculin skin test program in hospitals
      and health departments.
AB  - OBJECTIVE: To determine (1) the annual costs of implementing and maintaining
      tuberculin skin test (TST) programs at participating study sites, (2) the cost of
      the TST program per healthcare worker (HCW), and (3) the outcomes of the TST
      programs, including the proportion of HCWs with a documented TST conversion and
      the proportion who accepted and completed treatment for latent TB infection,
      before and after the implementation of staffTRAK-TB software (Centers for Disease
      Control and Prevention, Atlanta, GA). DESIGN: Cost analysis in which costs for
      salaries, training, supplies, radiography, and data analysis were collected for
      two 12-month periods (before and after the implementation of staffTRAK-TB).
      SETTING: Four hospitals (two university and two city) and two health departments
      (one small county and one big city). RESULTS: The annual cost of implementing and
      maintaining a TST program ranged from dollars 66,564 to dollars 332,728 for
      hospitals and dollars 92,886 to dollars 291,248 for health departments. The cost
      of the TST program per HCW ranged from dollars 41 to dollars 362 for hospitals
      and dollars 176 to dollars 264 for health departments. CONCLUSIONS: Costs
      associated with implementing and maintaining a TST program varied widely among
      the participating study sites, both before and after the implementation of
      staffTRAK-TB. Compliance with the TB infection control guidelines of the Centers
      for Disease Control and Prevention may require a substantial investment in
      personnel time, effort, and commitment.

PMID- 14649769
TI  - Utility of dual skin tests to evaluate tuberculin skin test reactions of 10 to 14
      mm in healthcare workers.
AB  - OBJECTIVE: To define the utility of 10- to 14-mm reactions to a Mycobacterium
      tuberculosis purified protein derivative (PPD) skin test for healthcare workers
      (HCWs). DESIGN: Blinded dual skin testing, using PPD and M. avium sensitin, of
      HCWs at a single medical center who had a 10- to 14-mm reaction to PPD when
      tested by personnel from the Occupational Health Department as part of routine
      annual screening. SETTING: A single tertiary-care academic medical center.
      PARTICIPANTS: Employees of the medical center who underwent routine annual PPD
      screening and were identified by the Occupational Health Department as having a
      reaction of 10 to 14 mm to PPD. RESULTS: Nineteen employees were identified as
      candidates and 11 underwent dual skin testing. Only 4 (36%) had repeat results
      for PPD in the 10- to 14-mm range, whether read by Occupational Health Department
      personnel or study investigators. For only 5 (45%) of the subjects did the
      Occupational Health Department personnel and study investigators concur (+/- 3
      mm) on the size of the PPD reaction. Two of the 4 subjects with reactions of 10
      to 14 mm as measured by the study investigators were M. avium sensitin dominant,
      1 was PPD dominant, and 1 was nondominant. CONCLUSION: A reaction of 10 to 14 mm
      to PPD should not be used as an indication for the treatment of latent
      tuberculosis (TB) infection in healthy HCWs born in the United States with no
      known exposure to TB.

PMID- 14649770
TI  - Potential nosocomial exposure to Mycobacterium tuberculosis from a bronchoscope.
AB  - OBJECTIVE: To investigate a possible nosocomial outbreak of tuberculosis (TB).
      DESIGN: Retrospective cohort study. SETTING: Community hospital. METHODS: We
      reviewed medical records, hospital infection control measures, and potential
      locations of nosocomial exposure. We examined the results of acid-fast bacilli
      (AFB) smears, cultures, and drug susceptibility testing, and performed a DNA
      fingerprint analysis. We observed laboratory specimen processing procedures and
      bronchoscope disinfection procedures. We also reviewed bronchoscopy records.
      RESULTS: In October 2000, three patients had bronchoscopy specimen cultures that
      were positive for Mycobacterium tuberculosis. Of the three, only one had clinical
      signs and symptoms consistent with TB and positive AFB sputum smears. The other
      two did not have signs and symptoms consistent with TB and had no known exposure
      to individuals with infectious TB. The three M. tuberculosis isolates had
      matching DNA fingerprints. No evidence of laboratory cross-contamination was
      identified. The three culture-positive specimens of M. tuberculosis were
      collected with the same bronchoscope within 9 days. This bronchoscope was
      inadequately cleaned and disinfected between patients, and the automated
      reprocessor used was not approved for use with the hospital bronchoscope.
      CONCLUSIONS: One of the bronchoscopes at this hospital was contaminated with M.
      tuberculosis during bronchoscopy of an AFB-smear-positive patient. Subsequent
      specimen contamination likely occurred because the bronchoscope had been
      inadequately cleaned and disinfected. Patients who subsequently underwent
      bronchoscopy were also potentially exposed to M. tuberculosis from this
      bronchoscope.

PMID- 14649771
TI  - Relative versus absolute noncontagiousness of respiratory tuberculosis on
      treatment.
AB  - OBJECTIVE: To assess the validity of current estimates of the noncontagiousness
      of sputum smear-positive respiratory tuberculosis (TB) on treatment. DESIGN: A
      descriptive analysis of the mycobacteriologic response to treatment. SETTING: A
      TB inpatient unit of a Canadian hospital. PATIENTS: Thirty-two HIV-seronegative
      patients with moderate to advanced sputum smear-positive respiratory TB were
      treated with uninterrupted, directly observed, weight-adjusted isoniazid,
      rifampin, and pyrazinamide. Each patient's initial isolate was drug susceptible
      and each patient's sputum mycobacteriology was systematically followed until 3
      consecutive sputum smears were negative on 3 separate days. RESULTS: The time to
      smear conversion varied remarkably (range, 8 to 115 days; average, 46 days) and
      was influenced by sputum sampling frequency. Only 3 patients (9.4%) had smear
      conversions by 14 days and only 8 (25%) had smear conversions by 21 days, the
      average time it took for drug susceptibility test results to become available.
      During the first 21 days of treatment, the semiquantitative sputum smear score
      decreased rapidly and the time to detection of positive cultures doubled. Within
      the time to smear conversion, virtually all smear-positive specimens (98%) were
      culture positive and only 34% of the patients had culture conversions (ie, 3
      consecutive negative cultures). CONCLUSION: Current estimates of the
      noncontagiousness of sputum smear-positive respiratory TB on treatment (for 14
      days, for 21 days, or until smear conversion) are estimates of relative
      noncontagiousness. They do not signal absolute noncontagiousness (culture
      conversion). Semiquantitative smear and time-to-detection data suggest that
      respiratory isolation beyond 21 days of optimal treatment should be selective.

PMID- 14649772
TI  - Use of, effectiveness of, and attitudes regarding influenza vaccine among house
      staff.
AB  - OBJECTIVE: To determine influenza vaccination rates, vaccine effectiveness, and
      factors influencing vaccination decisions among house staff. DESIGN: Cross
      sectional survey. SETTING AND PARTICIPANTS: All residents registered at the
      University of Toronto were surveyed after the 1999-2000 influenza season. Of the
      1,159 questionnaires mailed, 670 (58%) could be evaluated. RESULTS: Influenza
      like illnesses were reported by 36% of house staff. The vaccination rate was 51%
      among respondents, being highest for community and occupational medicine and
      pediatric staff (77% and 75%) and lowest for psychiatry, surgery, and radiology
      staff (32%, 36%, and 36%). Vaccinees reported significantly fewer episodes of
      illness (42 vs 54 per 100 subjects; P = .03) and fewer days of illness (272 vs
      374 per 100 subjects; P = .02); absenteeism was not different (63 vs 69 per 100
      subjects; P = .69). Self-protection was the most common reason for vaccination.
      Vaccinees believed the vaccine was more effective than did non-vaccinees (P <
      .01). Non-vaccinees considered influenza-like symptoms the most important side
      effect of the vaccine. Busy schedules and inconvenience were the most common
      reasons for not getting vaccinated. Overall, 44% of house staff believed the
      influenza vaccine should be mandatory. CONCLUSIONS: Influenza-like illness was
      common among house staff. They tended to work through their illnesses,
      potentially putting patients at risk. They were motivated mostly by self
      protection and did report a benefit. Despite busy schedules and an unfounded fear
      of getting influenza symptoms from the vaccine, many thought the vaccine should
      be mandatory.

PMID- 14649773
TI  - Correlation between healthcare workers' knowledge of influenza vaccine and
      vaccine receipt.
AB  - OBJECTIVE: Influenza vaccine receipt by healthcare workers (HCWs) is important
      because HCWs are at risk for occupational exposure to influenza and may act as
      vectors in the nosocomial transmission of influenza. HCWs were surveyed to
      determine whether belief in commonly held influenza vaccine misconceptions was
      associated with influenza vaccine acceptance. DESIGN: Cross-sectional study.
      SETTING: A large urban teaching hospital. METHOD: A self-administered survey was
      used to assess nursing and physician staff influenza vaccine knowledge, current
      vaccination status, and potential reasons for vaccine declination. RESULTS: Two
      hundred twelve of 215 surveys were completed. The overall influenza vaccination
      rate was 73%. Physician staff were significantly more likely to have been
      vaccinated compared with nursing staff (82% vs 62%, respectively; P = .0009).
      HCWs answering the 5 influenza vaccine basic knowledge questions correctly were
      significantly more likely to have been vaccinated than those responding
      incorrectly to any question (84% vs 64%, respectively; P = .002). This
      association was present in the nursing group where 80% of those answering the
      knowledge questions correctly were vaccinated, but only 49% of those answering
      incorrectly were vaccinated (P = .000005). However, in the physician group, there
      was no significant difference in the influenza vaccination rates between those
      answering correctly and those answering incorrectly (P = .459). CONCLUSION:
      Belief in commonly held influenza vaccine misconceptions was significantly
      associated with influenza vaccine declination among nursing staff and may act as
      a barrier to greater rates of influenza vaccination. Reasons for influenza
      vaccine nonreceipt may differ between nursing and physician staff.

PMID- 14649774
TI  - A preventable outbreak of pneumococcal pneumonia among unvaccinated nursing home
      residents in New Jersey during 2001.
AB  - OBJECTIVE: To characterize risk factors for invasive pneumococcal infection in a
      nursing home outbreak. DESIGN: Outbreak investigation, case-control study.
      SETTING: A 114-bed nursing home in New Jersey. PARTICIPANTS: Case-patients were
      nursing home residents hospitalized with febrile respiratory illness and
      radiographic findings consistent with pneumonia, and either sputum specimens
      positive for diplococci or blood cultures positive for Streptococcus pneumoniae,
      with illness onset during April 3-24, 2001. Control-patients were selected
      randomly from remaining residents without respiratory symptoms. METHODS: Chart
      reviews were performed for case-patients and control-patients. Serotyping and
      susceptibility testing were performed on S. pneumoniae isolates. Long-term-care
      facilities (LTCFs) were surveyed to assess compliance with a state regulation
      mandating pneumococcal vaccination of residents 65 years and older. RESULTS: Nine
      case-patients were identified, with a median age of 86 years (range, 78 to 100
      years). The median age of control-patients was 86 years (range, 58 to 95 years).
      No case-patients versus 9 (50%) control-patients received pneumococcal vaccine
      before the outbreak (OR, 0; CI95, 0-0.7). Recent antibiotic use, pneumonia
      history, and physical functioning were not associated with illness. Illness
      attack rate was 16% among all unvaccinated residents versus 0 among vaccinated
      residents. S. pneumoniae serotype 14, included in pneumococcal vaccine, was
      isolated from blood cultures of 7 case-patients. Of 361 LTCFs (42%) that replied
      to the survey, 28 (8%) were not complying with state immunization regulations.
      CONCLUSIONS: This outbreak occurred in an LTCF with low vaccine coverage.
      Implementing standing order programs, enforcing regulations, documenting
      vaccinations, and providing education might increase coverage among nursing home
      residents.

PMID- 14649775
TI  - Ventilator-associated pneumonia in a multi-hospital system: differences in
      microbiology by location.
AB  - OBJECTIVE: To determine whether there were differences in the microbiologic
      etiologies of ventilator-associated pneumonia in different clinical settings.
      DESIGN: Observational retrospective cohort study of microbiologic etiologies of
      ventilator-associated pneumonia from 1998 to 2001 in a multi-hospital system.
      Microbiologic results were compared between hospitals and between different
      intensive care units (ICUs) within hospitals. SETTING: Three hospitals--one
      pediatric teaching hospital, one adult teaching hospital, and one community
      hospital--in one healthcare system in the midwestern United States. PATIENTS:
      Patients at the target hospitals who developed ventilator-associated pneumonia
      and for whom microbiologic data were available. RESULTS: Seven hundred fifty
      three episodes of ventilator-associated pneumonia had culture data available for
      review. The most common organisms at all hospitals were Staphylococcus aureus
      (28.4%) and Pseudomonas aeruginosa (25.2%). The pediatric hospital had higher
      proportions of Escherichia coli (9.5% vs 2.3%; P < .001) and Klebsiella
      pneumoniae (13% vs 3.1%; P < .001) than did the adult hospitals. In the pediatric
      hospital, the pediatric ICU had higher P aeruginosa rates than did the neonatal
      ICU (33.3% vs 17%; P = .01). In the adult hospitals, the surgical ICU had higher
      Acinetobacter baumannii rates (10.2% vs. 1.7%; P < .001) than did the other ICUs.
      CONCLUSIONS: Microbiologic etiologies of ventilator-associated pneumonia vary
      between and within hospitals. Knowledge of these differences can improve
      selection of initial antimicrobial regimens, which may decrease mortality.

PMID- 14649776
TI  - Impact of a program of intensive surveillance and interventions targeting
      ventilated patients in the reduction of ventilator-associated pneumonia and its
      cost-effectiveness.
AB  - OBJECTIVE: We hypothesized that a program of prospective intensive surveillance
      for ventilator-associated pneumonia (VAP) and concomitant implementations of
      multimodal, multidisciplinary preventive and intervention strategies would result
      in a reduction in the incidence of VAP and would be cost-effective. SETTING:
      Medical and surgical intensive care units (ICUs) in a university teaching
      hospital. INTERVENTIONS: All ventilated patients in the medical and surgical ICUs
      were monitored for VAP from January 1997 through December 1998. Interventions
      including elevation of the head of the bed, use of sterile water and replacement
      of stopcocks with enteral valves for nasogastric feeding tubes, and prolongation
      of changing of in-line suction catheters from 24 hours to as needed were
      implemented. RESULTS: The rates of VAP decreased by 10.8/1,000 ventilator-days in
      the medical ICU (CI95, 4.65-16.91) and by 17.2/1,000 ventilator-days in the
      surgical ICU (CI95, 2.85-31.56) when they were compared for 1997 and 1998. With
      the use of the estimated cost of a VAP of dollars 4,947 from the literature, the
      reduction resulted in cost savings of dollars 178,092 and dollars 148,410 in the
      medical and surgical ICUs, respectively, for a total of dollars 326,482. In
      addition, dollars 25,497 was saved due to the lengthening of the time for the
      change of in-line suction catheters, resulting in a cost savings of dollars
      351,979. This total cost savings of dollars 351,979 minus the cost of enteral
      valves of dollars 2,100 resulted in total net savings of dollars 349,899.
      CONCLUSION: Intensive surveillance and interventions targeted at ventilated
      patients resulted in reduction of VAP and appeared to be cost-effective.

PMID- 14649777
TI  - Ventilator-associated pneumonia at a tertiary-care center in a developing
      country: incidence, microbiology, and susceptibility patterns of isolated
      microorganisms.
AB  - OBJECTIVE: Ventilator-associated pneumonia (VAP) complicates the course of up to
      24% of intubated patients. Data from the Middle East are scarce. The objective of
      this study was to evaluate the incidence, microbiology, and antimicrobial
      susceptibility patterns of isolated microorganisms in VAP in a developing
      country. DESIGN: Prospective observational cohort study. SETTING: The American
      University of Beirut Medical Center, a tertiary-care center that serves as a
      major referral center for Lebanon and neighboring countries. PATIENTS: All
      patients admitted to the intensive care and respiratory care units from March to
      September 2001, and who had been receiving mechanical ventilation for at least 48
      hours, were included in the study. Results of samples submitted for culture were
      recorded and antimicrobial susceptibility testing of isolated pathogens was
      performed. RESULTS: Seventy patients were entered into the study. The incidence
      of VAP was 47%. Gram-negative bacilli accounted for 83% of all isolates. The most
      commonly identified organism was Acinetobacter anitratus, followed by Pseudomonas
      aeruginosa. Fifty percent of all gram-negative bacterial isolates were classified
      as antibiotic resistant. Compared with patients without VAP, patients with VAP
      remained intubated for a longer period and stayed in the intensive care unit
      longer. VAP was not associated with an increased mortality rate. CONCLUSION:
      Compared with other studies, the results from this referral center in Lebanon
      indicate a higher incidence of VAP and a high prevalence of resistant organisms.
      These data are relevant because they direct the choice of empiric antibiotic
      therapy for VAP.

PMID- 14649778
TI  - Is cutaneous tuberculosis infectious? A case presentation and practical
      management plan.
AB  - Infection control measures for cutaneous tuberculosis in the absence of pulmonary
      disease are problematic. Delays in diagnosis can lead to the exposure of many
      individuals. This article describes a case of cutaneous tuberculosis and the
      subsequent contact investigation. Strategies for infection control and their
      practicality are discussed.

PMID- 14649779
TI  - Risk of acquiring influenza A in a nursing home from a culture-positive roommate.
AB  - Influenza A was cultured in 62 double rooms. The roommate was infected in 12
      (19.4%). During 3,294 resident-seasons, influenza was cultured in 208 single
      rooms (6.3%). Those who lived in double rooms with a culture-positive roommate
      had a 3.07 relative risk (CI95, 1.61-5.78) of acquiring influenza.

PMID- 14649780
TI  - What can we learn from consumer studies and qualitative research in the treatment
      of eating disorders?
AB  - The aim of this paper is to review all qualitative research and questionnaire
      surveys with people who have experienced an eating disorder or received treatment
      for it. Studies were identified on PubMed and PsychInfo. Twenty-three studies
      were identified and key findings are reviewed. Support and understanding are
      critical aspects of treatment perceived as helpful. Empathic relationships,
      whether professional or non-professional, were reported as essential to recovery.
      Psychological interventions (counselling and therapy) are the most popular and
      perceived as the most helpful. Many patients report that "medical interventions"
      were unhelpful. Interventions which focus exclusively on weight are reported
      negatively and many studies identify the importance of addressing wider issues
      than food and weight in treatment.

PMID- 14649781
TI  - Cognitive behavioural therapy for obesity: one-year follow-up in a clinical
      setting.
AB  - Cognitive behavioural therapy (CBT) is the most comprehensive means of medically
      treating obesity, but only few data have so far been published concerning its
      long-term effectiveness. We here report our experience of 1068 consecutive
      patients (868 females) treated with CBT at a university-based obesity centre. The
      patients were enrolled into three different programmes: a 14-week LEARN programme
      (672 patients), a 16-week MOB programme for the morbidly obese (259 patients), or
      a 20-week BINGE programme for subjects affected by binge eating (137 patients).
      Eighty-five percent of the subjects completed the weekly programmes. The
      percentage of patients attending the scheduled control visits during the 1-year
      follow-up gradually decreased, being very low in the BINGE group (10%). The
      percentage weight loss was an average of 6% during the weekly courses, being
      higher in the MOB programme; by the end of the weekly sessions, it exceeded 10%
      of initial body weight in 22% of cases and increased to 36% during the follow-up.
      The cumulative probability of follow-up was higher among the patients undergoing
      the MOB and LEARN programmes than among the BINGE patients (p < 0.0001), and
      decreased with the increasing severity of obesity. Female gender and a weight
      loss of > 10% i.b.w. increased compliance to follow-up. The study further
      demonstrates the difficulty of achieving compliance to chronic management of
      obesity and the critical role of binge eating disorder in the medium-term
      treatment of obesity. Strategies are needed to improve adherence to a follow-up
      protocol.

PMID- 14649782
TI  - The orexigram in patients affected by morbid obesity: a preliminary report on
      daily hunger sensation before bariatric surgery.
AB  - OBJECTIVE: The present study investigated the orexigram, the time-qualified self
      rated estimate of hunger sensation (HS), in patients affected by morbid obesity
      (MO) with the aim of detecting how daily HS behaves before morbidly obese
      patients (MOP) undergo bariatric surgery (BS). This article is therefore a
      preliminary report as it is necessary to make subsequent comparisons with post-BS
      orexigrams. Preoperative orexigrams may be helpful in selecting the MOPs who are
      candidates for surgical treatment. MATERIALS AND METHODS: Ten MOPs (five males
      and five females, with a mean age of 34 +/- 11 yr and a mean BMI of 49.32 +/-
      7.26 kg/m2), and 19 clinically healthy control subjects (CHS: nine males and ten
      females, with a mean age of 24 +/- 2 yr and a mean BMI of 21.00 +/- 1.70 kg/m2)
      gave their informed consent to participate in the study. All of the study
      participants were asked to compile a 24-h orexigram, which was then biometrically
      analysed by means of: 1) conventional methods for parametric statistics; 2)
      rhythm analysis for their circadian rhythms; and 3) spectral analysis for their
      harmonic structure. RESULTS: The orexigrams of the MOPs had significantly
      increased mean daily levels (daily hyperorexia), retained their circadian
      periodicity despite an increase in mesor, and were consistently modified in their
      ultradian spectral harmonic components. CONCLUSIONS: The results show that the
      studied MOPs complain of a daily hyperorexia that is still perceived
      circadically. This perception is a structured abnormality, as demonstrated by the
      consistent changes in the spectral analysis, and so MOPs can be diagnosed as
      being affected by so-called "hyperorectic obesity". It will be interesting to see
      whether or not presurgical hyperorexia in MOPs is corrected by BS: if so,
      hyperorexia may become an additional indication, and presurgery orexigrams could
      be suggested as an additional means of selecting the hyperorectic MOPs who are
      candidates for surgical treatment.

PMID- 14649783
TI  - Binge eating behaviours, depression and weight control strategies.
AB  - The aim of this paper was to explore the relationships between depressive
      symptoms and weight control strategies in DSM-IV eating disordered patients with
      binge eating behaviours. We hypothesised that weight control strategies
      characterised by a loss of control, such as vomiting and purging, may be
      clinically associated with increased levels of depression. The study population
      consisted of 402 consecutive outpatients: 27 with binge eating/purging anorexia
      nervosa (AN-BN), 213 with purging bulimia nervosa (BN-P), 73 with non-purging
      bulimia nervosa (BN-NP), and 89 with binge eating disorder (BED). The severity of
      depression was measured using the Beck Depression Inventory (BDI), and binge
      eating behaviours were investigated using the self-report scale for bulimic
      behaviours. In the sample as a whole, the severity of depression significantly
      correlated with the severity of binge eating behaviours, but no significant
      differences were found in the severity of depression by diagnostic sub-types. In
      order to avoid the confounding erasing effect of time, a smaller sample of
      patients with a short history of binge eating behaviours was further explored.
      Furthermore, because weight control strategies and the eating disorder diagnostic
      sub-types overlapped imperfectly, the patients were compared on the basis of
      presence or absence of strategies reflecting an active attempt to master the
      weight gain due to bingeing behaviours. The patients adopting active control
      strategies (N = 14) had significantly less severe depressive symptoms than those
      adopting non-active weight control strategies (N = 39). Finally, the Authors
      discuss some hypotheses concerning the defensive role of weight control
      strategies and the impact of illness duration on the clinical expression of
      depression in eating disordered patients.

PMID- 14649784
TI  - Plasma ghrelin levels and malnutrition: a comparison of two etiologies.
AB  - Ghrelin is a peptide hormone that is involved in regulating growth hormone
      secretion as well as food intake and energy homeostasis. The aim of this study
      was to compare changes in plasma ghrelin levels in patients with malnutrition due
      to anorexia nervosa (AN) or short bowel syndrome (SBS). Blood samples for
      laboratory analyses were taken from 16 AN patients (plus 13 comparable healthy
      controls) and 27 SBS patients (plus 13 comparable healthy controls) after an
      overnight fast. In comparison with their respective control groups, plasma
      ghrelin levels were increased in the AN patients (p < 0.05) and significantly
      decreased in the patients with SBS (p < 0.01). These results suggest that
      quantitative ghrelin secretion in the gut wall is important in determining
      ghrelin concentrations in the systemic circulation.

PMID- 14649785
TI  - Four-year follow-up of guided self-change for bulimia nervosa.
AB  - The aim of this follow-up study was to evaluate the longer-term effectiveness of
      guided self-care for bulimia nervosa. In the original trial, 62 patients with DSM
      III-R bulimia nervosa were randomly assigned to: a) a self-care manual plus eight
      fortnightly sessions of cognitive behavioural therapy (guided self-change); or b)
      16 weekly sessions of cognitive behavioural therapy (CBT). Twenty-eight of these
      patients (45% of the original cohort) were involved in this follow-up study based
      on personal interviews by experts and self-rated instruments; the majority of the
      others could not be traced, but their pre- and post-treatment variables were not
      different from those of the follow-up patients. After an average follow-up of
      54.2 months (SD 5.8), significant improvements were achieved or maintained in
      both groups in terms of the main outcome measures: eating disorder symptoms based
      on expert ratings (Eating Disorder Examination sub-scores for overeating,
      vomiting, dietary restraint, and shape and weight concerns), self report (Bulimic
      Investigatory Test Edinburgh), and a global five-point severity scale. There was
      also an improvement in the subsidiary outcome variables: Beck's Depression
      Inventory, the Self-concept Questionnaire, and knowledge of nutrition, weight and
      shape. During the week before the follow-up examination, 66.7% of the patients in
      the guided self-change group and 61.5% of those in the CBT group had not binged,
      vomited or abused laxatives. Guided self-change incorporating a self-care manual
      is an approach that can be as effective as standard cognitive behavioural therapy
      in the long-term, and can reduce the amount of therapist contact required.

PMID- 14649786
TI  - Therapeutic outcome of adjustable gastric banding in morbid obese patients.
AB  - We examined 77 obese patients treated with bariatric surgery in order to analyse
      treatment success, and compare those with a good or a poor outcome. The subjects,
      who were recruited one year after undergoing adjustable gastric banding, were
      asked questions concerning their sociodemographic status, postoperative course,
      past and present weight status, eating behaviours and difficulties in changing
      eating habits. Furthermore, we also used two body image questionnaires, and
      considered the patients' evaluations of positive and negative changes, as well as
      their wishes for the future. There were no preoperative differences between the
      71% of patients in the good outcome group and the 29% in the poor outcome group.
      With regard to the postoperative course, the poor outcome group had more problems
      in adapting to new eating behaviours, experienced significantly more post
      surgical complications, and had a persistently negative body evaluation. Both
      groups were satisfied with their achieved weight loss achieved, and their
      improved self-esteem and mobility. Adjustable gastric banding seems to be
      successful in inducing weight loss and allowing a better quality of life.
      However, factors such as postoperative complications, the ability and willingness
      to adopt new eating attitudes, and an improved body image seem to be crucial for
      therapeutic outcome.

PMID- 14649787
TI  - Some features of mothers of patients with eating disorders.
AB  - The aim of this study was to compare some of the characteristics of 50 mothers of
      patients with an eating disorder (ED) with those of a control group of 30 mothers
      of non-consulting adolescents. In comparison with the control group, the
      patients' mothers had higher scores for the bulimic factor of the Eating
      Attitudes Test-26, more frequent binge eating episodes, more eating disorder
      symptoms, more depression episodes, a higher incidence of bottle-fed daughters,
      provoked abortions and poor mother-daughter relationships with their own mothers.
      We recommend one-to-one diagnostic interviews with patients' mothers at the
      beginning of consultations.

PMID- 14649788
TI  - Beauty is as beauty does: body image and self-esteem of pageant contestants.
AB  - Self-esteem, dieting, and body image of 131 female beauty pageant contestants
      (mean age 26.0 years) from 43 states were examined by an anonymous survey. Most
      (89.6%) reported being a pageant finalist or winner and 55.2% had competed at the
      nationa/international level Over one-fourth (26%) of the women had been told or
      perceived they had an eating disorder which reportedly began at 16.25 years.
      Almost half (48.5%) reported wanting to be thinner and 57% were trying to lose
      weight. Higher self-esteem scores were significantly associated with increased
      level of competition (i.e.: from local to international pageants), but not with
      the number of times the women were pageant finalists or winners. Future study is
      warranted to determine how pageant participation influences self-esteem, body
      image, and the development of eating disorders.

PMID- 14649789
TI  - Body dissatisfaction and dieting in 4,952 Norwegian children aged 11-15 years:
      less evidence for gender and age differences.
AB  - A number of studies have shown that dieting and body dissatisfaction are highly
      frequent among adolescents. We here describe the relationship between dieting and
      body dissatisfaction in 4,952 children selected from the 11, 13 and 15 year age
      cohorts of the Norwegian national sample in the multinational WHO survey "Health
      Behavior in School Children". Body dissatisfaction was defined as the subjective
      experience of being a bit or much too fat and, using this definition, about 20%
      of the boys reported body dissatisfaction and 7% that they were on a diet. About
      37% of the girls reported body dissatisfaction and 15% that they were on a diet.
      Within the age cohorts, respectively 22%, 30% and 32% reported body
      dissatisfaction, whereas about 40% overall indicated no body dissatisfaction.
      Being on a diet was reported by 8% of the 11-year olds, and subsequently
      increased to 10% (13 years) and 14% (15 years). Multiple regression analysis
      showed that body dissatisfaction explained 33% of the variance in dieting
      behaviour, and that the overall effect of gender and age was small. Dieting and
      body dissatisfaction should therefore be recognised as being equally important
      among boys, and be counteracted within the framework of a health promotion
      strategy aimed at the general adolescent population.

PMID- 14649790
TI  - Adolescents and eating disorders: an examination of a day treatment program.
AB  - OBJECTIVE: In this study, we report on our day treatment program (DTP) for
      adolescents and young adults with eating disorders (EDs). METHOD: Data for the 82
      female patients in DTP were examined, compared across ED diagnosis and by age
      (adolescents vs. young adults). At admission, patients completed the Eating
      Disorder Inventory-2 (EDI-2) and the Beck Depression Inventory (BDI) and the
      Family Adaptability and Cohesion Evaluation Scale- II (FACES-II). RESULTS: Forty
      nine percent of patients successfully completed the day program and 13% required
      hospitalization following day treatment. Overall, there were no significant
      differences between the adolescents and adults at discharge of the day program.
      DISCUSSION: With shortened inpatient (IP) hospitalizations, DTPs can provide the
      long-term care required by many adolescent patients for psychological and
      physical recovery. This may be particularly important for the development of
      children and adolescents.

PMID- 14649791
TI  - Directives in anorexia nervosa: use of the "Ulysses Agreement".
AB  - The course of anorexia nervosa frequently has episodes of exacerbation during
      which motivation and insight are reduced, cognition is impaired and treatment
      resistance is increased. Formalizing a directive to be used during these episodes
      when the patient has greater motivation and insight is one way of reducing
      treatment resistance. We describe a form of directive, called the "Ulysses
      Agreement".

PMID- 14649792
TI  - The photonic opal--the jewel in the crown of optical information processing.

PMID- 14649793
TI  - The complexity of catalysis: origins of enantio- and diastereocontrol in sulfur
      ylide mediated epoxidation reactions.
AB  - The reaction of chiral sulfur ylides with aldehydes and ketones has emerged as a
      useful asymmetric process for the synthesis of epoxides. Processes employing
      either catalytic or stoichiometric amounts of sulfides have been developed.
      Although a large number of chiral sulfur ylides have been tested in the
      epoxidation process, only a few have delivered high diastereo- and enantio-
      selectivity. This review examines the factors that influence stereocontrol
      (steric hindrance of the sulfide, ylide conformation, ylide face selectivity,
      reversibility of betaine formation, solvent, and metal salts). This analysis
      leads to the conclusion that high reversibility in betaine formation leads to
      high diastereoselectivity but low enantioselectivity, and non-reversible betaine
      formation leads to low diastereoselectivity and high enantioselectivity (provided
      that other criteria are met). To achieve both high diastereoselectivity and high
      enantioselectivity simultaneously, requires non-reversible formation of the anti
      betaine and reversible formation of the syn-betaine. Thus, factors that influence
      the degree of reversibility in betaine formation are critically important since
      with subtle changes in reaction conditions (solvent, temperature, metal ions)
      both high enantio- and diastereoselectivity can often be achieved.

PMID- 14649794
TI  - Palladium-containing perovskites: recoverable and reuseable catalysts for Suzuki
      couplings.
AB  - Palladium-containing perovskites (LaFe0.57Co0.38Pd0.05O3) have been exploited as
      recoverable and reuseable catalysts in Suzuki coupling reactions; residual levels
      of Pd after removal of the catalyst by filtration are low (2 ppm) despite
      evidence that the reaction is occurring via a homogeneous process.

PMID- 14649795
TI  - Rotavap simulation and the estimation of boiling points.
AB  - A Java applet that predicts solute losses during evaporation from a binary or
      ternary mixture has been developed which gives good agreement with experiment and
      can be used to estimate the boiling points of solutes, making use of information
      which is often collected and then discarded
      (http://www.ch.cam.ac.uk/magnus/rotavap/).

PMID- 14649796
TI  - The generation and trapping of organozinc carbenoids from N-diethoxymethyl
      amides: a new amidocyclopropanation reaction.
AB  - Amidocyclopropanes are readily prepared by reaction of N-diethoxymethyl amides
      with alkenes in the presence of zinc amagalm, zinc chloride and
      chlorotrimethylsilane.

PMID- 14649797
TI  - Medium ring synthesis by radical ipso-substitution.
AB  - A new approach to eight and nine membered ring synthesis is described in which a
      radical ipso-substitution reaction features as a key step.

PMID- 14649798
TI  - Carbonate and oxalate dianions as prolific hydrogen-bond acceptors in
      supramolecular assembly.
AB  - In the new inclusion compound [(C2H5)4N+]2 x CO3(2-) x 7(NH2)2CS, the carbonate
      ion is surrounded by twelve convergent NH donor groups from six thiourea
      molecules to form a hydrogen-bonded aggregate shaped like two concave three
      leaved propellers sharing a common core, whereas in [(n-C3H7)4N+]2 x C2O4(2-) x
      4(NH2)2CS the oxalate ion serves as a hub for binding four thiourea molecules to
      generate a cross-shaped structural motif.

PMID- 14649799
TI  - Vapour diffusion hydrolysis of a self-assembled silylated organogel, the OG-HG
      transcription process: a new way to cast and handle fluorescent silsesquioxane.
AB  - A new method of hydrolysis-polycondensation of silsesquioxanes, the OG-HG (Organo
      Gel-Hybrid Gel or Organised Gel-Hydrolysed Gel) process allows the transcription
      of the supramolecular architecture of organogels to corresponding hybrid
      silsesquioxanes.

PMID- 14649800
TI  - Assembly of a polyoxometalate into an anisotropic gel.
AB  - The self-assembly of the polyoxomolybdate [MnMo6O18[(OCH2)3CNHCO(4-C5H4N)]2]3-
      and [PdCl2(PhCN)2] yields a transparent and birefringent gel.

PMID- 14649801
TI  - Aggregation of metallo-supramolecular architectures by metallo-assembled hydrogen
      bonding sites.
AB  - Metal-ligand interactions are used not only to design metallo-supramolecular
      architectures but also to assemble multiple hydrogen bond sites at the periphery
      of these architectures. The hydrogen bond sites aggregate the architectures into
      polymeric arrays with the selection of anion determining whether this is self H
      bond aggregation or anion-mediated H-bond aggregation.

PMID- 14649802
TI  - A cationic 24-MC-8 manganese cluster with ring metals possessing three oxidation
      states [Mn(II)4Mn(III)6Mn(IV)2(mu4-O)2(mu3-O)4(mu3-OH)4(mu3
      OCH3)2(pko)12](OH)(ClO4)3.
AB  - Reaction of Mn(ClO4)2 with di-pyridyl ketone oxime, (2-py)2C=NOH, gives the novel
      cluster [Mn(II)4Mn(III)6Mn(IV)2(mu4-O)2(mu3-O)4(mu3-OH)4(mu3
      OCH3)2(pko)12](OH)(ClO4)3 1. It is the only example of a 24-MC-8, and the first
      metallacrown with ring metal ions in three different oxidation states. Magnetic
      measurements show antiferromagnetic behavior.

PMID- 14649803
TI  - Structural characterisation of the first mononuclear bismuth porphyrin.
AB  - A single carboxylate picket bismuth porphyrin has been characterised in the solid
      state as the first instance of a non-dimeric structure; the carboxylate picket,
      bent over the macrocycle, is coordinated to the bismuth, inducing a significant
      distortion of the porphyrin core.

PMID- 14649804
TI  - Single-molecule magnets: control by a single solvent molecule of Jahn-Teller
      isomerism in [Mn12O12(O2CCH2Bu(t))16(H2O)4].
AB  - Faster- and slower-relaxing versions of the title Mn12 compound have been
      obtained in pure forms that crystallize in the same space group and differ only
      in the identity of one lattice solvent molecule; solvent loss causes
      isomerization from the faster- to the slower-relaxing form.

PMID- 14649805
TI  - Dynamic combinatorial libraries of metalloporphyrins: templated amplification of
      disulfide-linked oligomers.
AB  - Disulfide-linked cyclic porphyrin oligomers from dimer to tetramer can be
      selected and amplified virtually quantitatively from a dynamic combinatorial
      library using bis-thiol substituted zinc(II) porphyrin units with appropriate
      amine donor templates.

PMID- 14649806
TI  - Significant promotional effect of CCl4 on fullerene yield in the graphite arc
      discharge reaction.
AB  - Addition of a small quantity (approximately 3%) of CCl4 to the He atmosphere of
      the graphite arc-discharge reaction revealed a marked increase in fullerene
      yield.

PMID- 14649807
TI  - Highly stereoselective synthesis of (-)-monatin, a high-intensity sweetener,
      using chelation-controlled nitrone cycloaddition.
AB  - Synthesis of (-)-monatin was achieved by chelation-controlled cycloaddition of
      nitrone 2 with allyl alcohol 3a in the presence of MgBr2-OEt2.

PMID- 14649808
TI  - HPLC separation of diastereomers of Ln(III)-ethylenepropylene-triamine
      pentaacetate complexes. Direct assessment of their water exchange rate.
AB  - The diastereomers of two Ln(III)-EPTPA derivatives have been separated by
      reversed-phase HPLC, and the water exchange rate on their Gd(III) complexes has
      been directly determined by 17O NMR (H5EPTPA = ethylenepropylene-triamine
      pentaacetic acid).

PMID- 14649809
TI  - Extended X-ray absorption fine structure (EXAFS) characterisation of dilute
      palladium homogeneous catalysts.
AB  - Highly dilute EXAFS characterisation for the elucidation of species involved in
      Heck chemistry is demonstrated; the major "monomer" species of Herrmann's acetate
      bridged phosphapalladadacycle is characterised and species present during the
      course of a 50 ppm [Pd] Pd(OAc)2/PBu(t)3 catalysed Heck reaction are presented.

PMID- 14649811
TI  - New dibenzofuran-bridged bis(amidoamine) and bis(ethylenediamine) ligands and
      their dinuclear zinc and aluminium complexes.
AB  - A new class of dibenzofuran-bridged bis(amidoamine) and bis(ethylenediamine)
      ligands are used to prepare structurally-characterized dinuclear zinc and
      aluminium complexes.

PMID- 14649810
TI  - Peptide-coated CdS quantum dots for the optical detection of copper(II) and
      silver(I).
AB  - Gly-His-Leu-Leu-Cys coated CdS quantum dots detected Cu2+ and Ag+ selectively
      with high sensitivity, below 0.5 microM.

PMID- 14649812
TI  - Synthesis of high quality inorganic fullerene-like BN hollow spheres via a simple
      chemical route.
AB  - High quality inorganic fullerene-like boron nitride hollow spheres (100-200 nm)
      have been successfully synthesized via a simple chemical route with a 30-40%
      yield of BN hollow spheres.

PMID- 14649813
TI  - Synthesis, characterization and catalytic activity of a Wilkinson's type metal
      organic-polyoxometalate hybrid compound.
AB  - A metal-organic-polyoxometalate hybrid compound with two functional centers
      consisting of a rhodium(I)bis(diphenylphospine) unit connected through two
      alkylene bridging groups to a lacunary Keggin type polyoxometalate was
      synthesized and used as an effective, recyclable hydrogenation catalyst in
      monophasic and aqueous biphasic reaction modes.

PMID- 14649814
TI  - Highly ordered three-dimensional large-pore periodic mesoporous organosilica with
      Im3m symmetry.
AB  - Highly ordered three-dimensional Im3m-type periodic mesoporous organosilica with
      a cavity size of 9.8 nm has been synthesized under strongly acidic media in the
      presence of inorganic salts using triblock copolymer F127 as the template and 1,2
      bis(trimethoxysilyl)ethane as the organically bridged silica source.

PMID- 14649815
TI  - La(1-x)Ba(1+x)GaO(4-x/2): a novel high temperature proton conductor.
AB  - In this communication we demonstrate high temperature proton conduction in the
      phase La(1-x)Ba(1+x)GaO(4-x/2), with conductivities significantly higher than
      reported for other phases containing tetrahedral ions, such as doped LaPO4.

PMID- 14649816
TI  - Thermodynamically controlled cyclisation reactions with double phenylsulfanyl
      migration.
AB  - Enantiomerically enriched C2-symmetric tetrols were synthesised by a route
      involving a 'self-metathesis' reaction with Grubbs' second-generation ruthenium
      catalyst; these tetrols produced interesting bicyclic products when rearranged
      under acidic conditions.

PMID- 14649817
TI  - Biotin grafting on boron-doped diamond.
AB  - Grafting of biotin on top of a polycrystalline boron-doped diamond layer was
      achieved by surface oxidation followed by an esterification reaction and revealed
      by fluorescently labelled streptavidin.

PMID- 14649818
TI  - Construction of a square-planar hydroperoxo-copper(II) complex inducing a higher
      catalytic reactivity.
AB  - A novel hydroperoxo-copper(II) complex with a square-planar geometry has been
      prepared, which has exhibited a higher selectivity and catalytic reactivity for
      dimethyl sulfide, in contrast to that with a trigonal-bipyramidal one.

PMID- 14649819
TI  - Telomestatin-induced stabilization of the human telomeric DNA quadruplex
      monitored by electrospray mass spectrometry.
AB  - Electrospray mass spectrometry (ESI-MS) was used to monitor the kinetics of
      duplex formation between the human telomeric DNA quadruplex and its complementary
      strand; the complexation of telomestatin to the G-quadruplex delays the unwinding
      of the quadruplex structure and formation of the duplex.

PMID- 14649821
TI  - A novel route for the synthesis of piperazine from N-(2,3
      dihydroxypropyl)ethylenediamine over composite photocatalysts.
AB  - Semiconductor loaded zeolite composite catalysts (5 wt% TiO2/Hbeta) have been
      used to photocatalytically synthesize piperazine from N-(2,3
      dihydroxypropyl)ethylenediamine with yields up to 59.0 mol%.

PMID- 14649820
TI  - Luminescent rhenium(I) diimine indole conjugates--photophysical, electrochemical
      and protein-binding properties.
AB  - Two novel luminescent rhenium(I) diimine indole complexes have been designed and
      their properties studied; these conjugates can be recognised by indole-binding
      proteins including bovine serum albumin, lysozyme and tryptophanase.

PMID- 14649822
TI  - High-performance blue electroluminescent devices based on 2-(4-biphenylyl)-5-(4
      carbazole-9-yl)phenyl-1,3,4-oxadiazole.
AB  - An electron transporting moiety (1,3,4-oxadiazole) and a hole transporting moiety
      (carbazole) were combined to create 2-(4-biphenylyl)-5-(4-carbazole-9-yl)phenyl
      1,3,4-oxadiazole (CzOxa), a three layer device with a configuration of ITO/TPD(50
      nm)/CzOxa(40 nm)/AlQ(40 nm)/Mg0.9Ag0.1(200 nm)/Ag(80 nm) which exhibited a blue
      emission peak at approximately 470 nm (x = 0.14, y = 0.19) with a maximum
      luminance of 26,200 cd m(-2) at a drive voltage of 15 V and a maximum luminous
      efficiency of 2.25 lm W(-1).

PMID- 14649823
TI  - Photoluminescence and electrochemiluminescence of a Ru(II)(bpy)3-quencher dual
      labeled oligonucleotide probe.
AB  - A molecular beacon oligonucleotide probe covalently labeled with Ru(II)(bpy)3 and
      Black Hole Quencher-2 is synthesized, and hybridization assays are performed
      using photoluminescence and electrochemiluminescence methods of excitation.

PMID- 14649824
TI  - Chiral sulfoxides in the enantioselective allylation of aldehydes with
      allyltrichlorosilane.
AB  - The use of chiral sulfoxides as Lewis base catalysts in the allylation of
      aldehydes with allyltrichlorosilane is reported.

PMID- 14649825
TI  - A highly enantioselective phase-transfer catalyzed epoxidation of enones with a
      mild oxidant, trichloroisocyanuric acid.
AB  - The enantioselective epoxidation can be carried out using trichloroisocyanuric
      acid (TCCA) as oxidant in the presence of chiral quaternary ammonium salt as a
      phase-transfer catalyst; treatment of chalcone derivatives with TCCA under mild
      conditions afforded the corresponding epoxy ketones in good yields with moderate
      to excellent enantioselectivities of up to 96%.

PMID- 14649826
TI  - Isolation of C-H...C(pi) complexes from the reaction of stable carbenes with
      hydrocarbons.
AB  - Several imidazolium-hydrocarbon salts have been isolated from the reaction of
      stable carbenes with hydrocarbons and some of the products have been structurally
      characterized showing ion pair formation in the solid state characterized by the
      presence of well defined and transferable C-H...C(pi) interactions.

PMID- 14649827
TI  - Production of vancomycin aglycone conjugated to a peptide carrier domain derived
      from a biosynthetic non-ribosomal peptide synthetase.
AB  - A method for attaching the vancomycin aglycone to a peptide carrier domain (PCD)
      is reported which involves reacting the apo-PCD produced in Escherichia coli with
      vancomycin aglycone-coenzyme A thioester, catalyzed by the phosphopantetheinyl
      transferase Sfp from Bacillus subtilis.

PMID- 14649828
TI  - RESS for the preparation of fluorinated porphyrin nanoparticles.
AB  - Rapid Expansion of Supercritical Solutions (RESS) was used to produce clean,
      surfactant-free nanoparticles (average size = 60 nm) of a fluorinated
      tetraphenylporphyrin from supercritical solutions with CO2.

PMID- 14649829
TI  - A versatile synthesis of new pyrimidinyl nitronyl nitroxides.
AB  - Pyrimidinyl nitronyl nitroxides where the bis-N-oxy fragment is included in a six
      membered ring were prepared from diacetonamine by a sequence of reactions
      including a Grignard reaction, a Ritter reaction and oxidation of the
      intermediate pyrimidine; the properties of the 2-phenyl-substituted
      representative are fully described.

PMID- 14649830
TI  - Novel synthetic method of phosphonamidate peptides and its application in peptide
      sequencing via multistage mass spectrometry.
AB  - Phosphonamidate peptides were prepared in good yields by reaction of
      ethoxy(phenyl)phosphinate with free peptides in a mixed solution of H2O, C2H5OH,
      Et3N and CCl4 at room temp.; their in situ electrospray ionization mass spectra
      exhibited high sensitivity compared with the free peptides, and sequential loss
      of amino acid residues of the sodiated phosphonamidate peptides from the C
      terminus was found in multistage ESI mass spectrometry. The results show that N
      phosphonyl derivatization combined with multistage ESI-MS is a powerful method
      for peptide sequencing.

PMID- 14649831
TI  - Novel approaches to synthesize self-supported ultrathin carbon nanowire arrays
      templated by MCM-41.
AB  - Ordered self-supported ultrathin carbon nanowire arrays with small mesopore sizes
      have been fabricated for the first time employing mesoporous silica MCM-41 as the
      templates, and two possible related mechanisms are proposed.

PMID- 14649832
TI  - Development of highly selective and sensitive probes for hydrogen.
AB  - Probes that react specifically with hydrogen peroxide to release chromophoric or
      fluorescent reporter groups were designed and synthesized.

PMID- 14649833
TI  - Quasi-solid dye sensitised solar cells filled with ionic liquid--increase in
      efficiencies by specific interaction between conductive polymers and gelators.
AB  - Photo-energy conversions for quasi-solid dye sensitised solar cells increased
      when gel electrolytes were combined with conductive polymers as counter
      electrodes and the conversion surpassed that for DSSCs equipped with conventional
      Pt counter electrodes.

PMID- 14649834
TI  - The effect of ruthenium(III) chloride on the formation of protonated parent ions
      in electrospray mass spectrometry.
AB  - We report the use of RuCl3 as an "alkali metal sponge". This is a general and
      highly efficient method for generating protonated parent ions for a variety of
      compounds that usually do not show this ion in electrospray mass spectrometry.
      This technique is demonstrated to be highly useful in "cleaning up" spectra from
      multiply metallated ions, thereby substantially improving the signal-to-noise
      ratio.

PMID- 14649835
TI  - Al-free Zr-zeolite beta as a regioselective catalyst in the Meerwein-Ponndorf
      Verley reaction.
AB  - Al-free Zr-zeolite beta catalyzes the transfer reduction of ketones to the
      corresponding alcohols in high yield and with exceptional stereocontrol. Notably,
      the catalyst is very robust and gives good results even with 10% water content in
      the reaction mixture.

PMID- 14649836
TI  - Metallo-phosphorylation of alkynes: reaction of alkynes with Cp2Zr(1-butene)(PR3)
      and chlorophosphate.
AB  - Reaction of alkynes with Cp2ZrBu2 and chlorophosphate in the presence PR3 to form
      zircono-alkenylphosphonates, which can be converted into various beta
      functionalized alkenylphosphonates.

PMID- 14649837
TI  - Polyaniline doped with modified gold nanoparticles and its electrochemical
      properties in neutral aqueous solution.
AB  - Doping polyaniline with COO(-)-modified gold nanoparticles by forming stable
      layer-by-layer multilayer films can shift its electroactivity to neutral pH. The
      films can electrocatalyze the oxidation of NADH and offer potential applications
      in other fields, e.g., optoelectronics or biosensing.

PMID- 14649838
TI  - Orientation-controlled assembly and solvothermal ion-exchange of layered double
      hydroxide nanocrystals.
AB  - The orientation-controlled LDH crystals on Si substrates were intercalated by
      dicarboxylate ions to give the anisotropic layer expansion.

PMID- 14649839
TI  - A ROMP-derived, polymer-supported chiral Schrock catalyst for enantioselective
      ring-closing olefin metathesis.
AB  - A permanently polymer-immobilised version of Schrock's molybdenum catalyst was
      realised via polymerisation of chiral 5,5'-bis(norborn-5-ene-2
      ylmethyleneoxymethyl)-3,3'-di-tert-butyl-6,6'-dimethylbiphen-2,2'-diol followed
      by reaction with the catalyst precursor Mo(N-2,6-i
      Pr2C6H3)(CHCMe2Ph)(OSO2CF3)2(CH3OCH2CH2OCH3); using this 5-, 6- and 7-membered
      heterocycles were synthesised via ring-closing metathesis (RCM) from (pro-)chiral
      substrates in high yields and ee with short reaction times; the catalyst shows
      low loss of molybdenum during RCM, and was easily separated and recycled.

PMID- 14649840
TI  - Insertion of pyridine into an iron-silicon bond: structure of the product
      Cp*(CO)Fe[eta3(C,C,C)-C5H5NSiMe2NPh2].
AB  - Heating a toluene solution of Cp*(CO)(C5H5N)FeSiMe2NPh2 led to insertion of
      pyridine into the iron-silicon bond to form Cp*(CO)Fe[eta3(C,C,C)
      C5H5NSiMe2NPh2].

PMID- 14649841
TI  - Binary solvent mixture adsorption as a characterisation tool to determine the
      hydrophilic/hydrophobic properties of multiwall carbon nanotubes.
AB  - A simple method is offered to quantitatively characterise the
      hydrophobic/hydrophilic properties of carbon nanotubes by measuring binary
      solvent mixture adsorption.

PMID- 14649842
TI  - Synthesis and crystal and molecular structure of a hydrido tetraamine cobalt(III)
      complex.
AB  - A moderately stable hydrido complex of a tetraaminecobalt(III) complex has been
      synthesised, a first, and the crystal structure and properties are reported.

PMID- 14649843
TI  - Adaptive test for testing the difference in survival distributions.
AB  - An adaptive test is proposed for the problem of testing the difference in
      survival distributions when the shape of the hazard ratio is unknown, hence the
      efficient test is unknown. The proposed adaptive test selects a test statistic
      from a finite set of the weighted logrank statistics T on the basis of the
      estimates of the efficiencies of the tests in T for given data. The efficiency
      estimator uses the length of the test based nonparametric confidence interval for
      the shift in a time transformed shift model. The suggested adaptive test is shown
      to be asymptotically efficient among the tests in T under the time transformed
      shift model and conditions commonly used in survival analysis. Simulations
      demonstrate that the adaptive test enjoys good small sample properties and in
      most situations is more powerful than the test using the maximum of the tests in
      T.

PMID- 14649844
TI  - Exact inference in the proportional hazard model: possibilities and limitations.
AB  - It is suggested that inference under the proportional hazard model can be carried
      out by programs for exact inference under the logistic regression model.
      Advantages of such inference is that software is available and that multivariate
      models can be addressed. The method has been evaluated by means of coverage and
      power calculations in certain situations. In all situations coverage was above
      the nominal level, but on the other hand rather conservative. A different type of
      exact inference is developed under Type II censoring. Inference was then less
      conservative, however there are limitations with respect to censoring mechanism,
      multivariate generalizations and software is not available. This method also
      requires extensive computational power. Performance of large sample Wald, score
      and likelihood inference was also considered. Large sample methods works
      remarkably well with small data sets, but inference by score statistics seems to
      be the best choice. There seems to be some problems with likelihood ratio
      inference that may originate from how this method works with infinite estimates
      of the regression parameter. Inference by Wald statistics can be quite
      conservative with very small data sets.

PMID- 14649845
TI  - Design of panel studies for disease progression with multiple stages.
AB  - A panel study consists of individuals who have data collected at periodic follow
      up visits or pre-specified time points following entry into the study. The
      objective of this paper is to consider design issues in a panel study when the
      response variable is the stage of disease, and with focus on the transition
      intensities. Important design issues include the choice of the time interval
      between follow-up visits and sample size considerations. We study the effects of
      time intervals between follow-up visits on the precision of the transition
      intensities estimators. We also consider the power of statistical tests on the
      ratio of transition intensities. Discussion is extended to incorporate
      heterogeneity in the population in which frailty is introduced to describe
      subject-specific transition intensities.

PMID- 14649846
TI  - Regression modeling with recurrent events and time-dependent interval-censored
      marker data.
AB  - In life history studies involving patients with chronic diseases it is often of
      interest to study the relationship between a marker process and a more clinically
      relevant response process. This interest may arise from a desire to gain a better
      understanding of the underlying pathophysiology, a need to evaluate the utility
      of the marker as a potential surrogate outcome, or a plan to conduct inferences
      based on joint models. We consider data from a trial of breast cancer patients
      with bone metastases. In this setting, the marker process is a point process
      which records the onset times and cumulative number of bone lesions which
      reflects the extent of metastatic bone involvement The response is also a point
      process, which records the times patients experience skeletal complications
      resulting from these bone lesions. Interest lies in assessing how the development
      of new bone lesions affects the incidence of skeletal complications. By
      considering the marker as an internal time-dependent covariate in the point
      process model for skeletal complications we develop and apply methods which allow
      one to express the association via regression. A complicating feature of this
      study is that new bone lesions are only detected upon periodic radiographic
      examination, which makes the marker processes subject to interval-censoring. A
      modified EM algorithm is used to deal with this incomplete data problem.

PMID- 14649847
TI  - Marginal regression of gaps between recurrent events.
AB  - Recurrent event data typically exhibit the phenomenon of intra-individual
      correlation, owing to not only observed covariates but also random effects. In
      many applications, the population may be reasonably postulated as a heterogeneous
      mixture of individual renewal processes, and the inference of interest is the
      effect of individual-level covariates. In this article, we suggest and
      investigate a marginal proportional hazards model for gaps between recurrent
      events. A connection is established between observed gap times and clustered
      survival data with informative cluster size. We subsequently construct a novel
      and general inference procedure for the latter, based on a functional formulation
      of standard Cox regression. Large-sample theory is established for the proposed
      estimators. Numerical studies demonstrate that the procedure performs well with
      practical sample sizes. Application to the well-known bladder tumor data is given
      as an illustration.

PMID- 14649848
TI  - Masters of their conditions: at the crossroads of health, culture and
      performance.
AB  - Achieving one's cultural or clinical identity is a matter of performance. The
      performing body is made through a series of apprenticeships that lead to mastery
      and then transmission. Performance, like culture and medicine, has its systems of
      learning, i.e. in the professions of the performing arts. This article examines
      the methodology of theater anthropology and other aspects of performance studies.
      Applications to intercultural work are described that make it possible for
      patient and healer to collaborate to master the condition.

PMID- 14649849
TI  - A Vietnamese man with selective mutism: the relevance of multiple interacting
      'cultures' in clinical psychiatry.
AB  - Multiple cultural variables have effects on the psychobiology and behavioral
      manifestations of illness, as do patient and physician perceptions of illness.
      The interaction among these variables is at the heart of clinical psychiatry.
      This case of a Vietnamese man with selective mutism underscores the relevance of
      the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations
      of illness and illness perceptions by patient and physician. The discussion
      focuses on how these cultures interact and play a crucial role in formulating
      diagnosis and treatment planning. Suggestions are given for shifts in medical
      education that will encourage relevant cultural paradigms to make their way into
      educational and clinical systems, which in turn should improve cultural
      competence in clinical psychiatry.

PMID- 14649850
TI  - 'Hit by the wind' and temperature-shift panic among Vietnamese refugees.
AB  - Surveying 60 Vietnamese patients with either current or past post-traumatic
      stress disorder, this article aims to phenomenologically characterize the
      syndrome of 'hit by the wind' in a multidimensional manner. This includes
      determining the patient conceptualization of the disorder, profiling 'hit by the
      wind' episodes suffered by patients in the previous month, and presenting case
      vignettes. Eighteen of the 60 patients (30%) suffered at least one episode of
      'hit by the wind' in the last month; all 18 patients had at least one episode of
      'hit by the wind' in the last month that met panic attack criteria. For the 18
      patients, 33 episodes of'hit by the wind' that met panic attack criteria were
      experienced in the previous month. For these 33 episodes, the most frequently
      reported DSM-IV panic attack symptoms were chills (100%; 33/33) and dizziness
      (88%; 29/33). Flashbacks played a role in the 'hit by the wind' episodes for 5 of
      the 18 patients (28%). In the discussion, a model of how the syndrome of 'hit by
      the wind' generates panic is adduced; also, possible Chinese origins of the
      disorder are discussed.

PMID- 14649851
TI  - Obsessive-compulsive disorder in Bali: the cultural shaping of a neuropsychiatric
      disorder.
AB  - Many psychiatric researchers believe that the clinical picture of obsessive
      compulsive disorder (OCD) shows little variability cross-culturally. This study
      examined the symptomatology and illness experience of 19 patients suffering from
      OCD in Bali, Indonesia. Patients were assessed using a semi-structured clinical
      interview. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was utilized for
      gauging symptomatology and severity of symptoms. A sub-sample of patients was
      interviewed using person-centered ethnographic techniques. Balinese culture
      strongly shaped symptomatic expression. The most common obsessional themes
      emphasized patients' obsessional need to know information about their social
      network, such as the identity and status of passers-by. Somatic obsessions and
      religious themes around witchcraft and spirits were also prominent. Psychiatric,
      indigenous and anthropological perspectives are contrasted to highlight the power
      and limitations of each to explain OCD.

PMID- 14649852
TI  - Prevalence of bulimic behaviours and eating attitudes in schoolgirls from
      Trinidad and Barbados.
AB  - We investigated eating attitudes and the prevalence of bulimic disorders in a
      group of 362 schoolgirls from the islands of Trinidad and Barbados using key
      questions from the Bulimia Investigatory Test, Edinburgh (BITE) and additional
      questions for the exploration of eating attitudes and dieting practices. A random
      sample of 92 girls were interviewed using the DSM-III-R Bulimia Diagnostic
      Interview. Only three subjects (0.8%) scored over the cut-off point on the BITE.
      None of the interviewees was diagnosed as having bulimia nervosa. Two hundred and
      forty-five girls (67.7%) reported being terrified of becoming fat and fat-fear
      was associated with higher Body Mass Index, dieting and exercising for losing
      weight. Girls of African origin were found to have a more unusual eating pattern
      and more concerns about their eating habits. The prevalence of bulimic disorders
      in Caribbean schoolgirls is still very low, but they are a population at
      increasing risk since they share the western ideals of slimness and engage in
      dieting behaviours.

PMID- 14649853
TI  - Psychosocial factors in chronic fatigue syndrome among Chinese Americans: a
      longitudinal community-based study.
AB  - Chronic fatigue syndrome (CFS) is a relatively new condition of unknown etiology.
      Research suggests that psychosocial factors such as perceived social support,
      life stress, and acculturation may significantly influence individuals who are
      prone to CFS. For 57 Chinese American individuals initially diagnosed with CFS,
      those who recovered after one year reported lower levels of life stress than
      those who did not recover. Effects of changes in perceived social support also
      appeared to be mediated by life stress.

PMID- 14649854
TI  - Comment on "A creative solution to the NIMBY problem" editorial by Jay Lehr and
      Herbert Inhaber, Ground Water 41, no. 4: 401.

PMID- 14649855
TI  - Aerobic, co-metabolic in situ biodegradation of chlorinated solvents and
      horizontal biosparge wells--a match made in bioremediation heaven.

PMID- 14649856
TI  - Air and water entrapment in the vicinity of the water table.
AB  - A laboratory tank was used to study entrapment of water in coarse sand lenses
      above the water table and of air in coarse sand lenses below the water table.
      Monitoring of these experiments involved a combination of visual inspection,
      measurement of moisture content, and measurement of air/water pressure. The
      medium consisted of coarse sand lenses with various degrees of vertical
      connectivity embedded within a fine sand matrix. Experiments were performed under
      conditions of both drainage (from a fully saturated medium) and imbibition.
      Observations during drainage included: (1) water was trapped in the coarse sand
      zones above the water table at heights significantly greater than anticipated
      from consideration of capillary rise in the coarse sand; (2) rapid drainage of
      these same coarse zones occurred when air penetrated into these zones through the
      surrounding fine sands; and (3) prior to the time of penetration of the coarse
      sand by air, water pressure in the coarse zone dropped significantly below
      atmospheric pressure. Observations during imbibition included: (1) entrapment of
      air within coarse sands below the water table, (2) the pore fluids in these zones
      varied spatially from predominantly air to predominantly water, and (3) pressure
      in the trapped air phase was significantly greater than pressure in the water
      phase in the surrounding fine sand. Overall, these results demonstrated
      significant sensitivity to the geometry of the coarse sand inclusions,
      particularly the vertical connectivity of the coarse sand lens.

PMID- 14649857
TI  - Correlation between nitrate contamination and ground water pollution potential.
AB  - AQUIPRO, a PC-based method, was used to assess aquifer vulnerability using
      digital water well logs. The AQUIPRO model is a parameter/factor weighting system
      for rating the pollution potential of an aquifer. This method uses the well
      depth, as well as the clay and partial clay thickness in a well, to generate
      pollution potential scores. In this model, aquifer protection increases as the
      AQUIPRO vulnerability scores increase and ground water pollution potential
      decreases. Computerized water well records of 2435 domestic wells with partial
      chemistry data were used to determine the ground water pollution potential of
      Kalamazoo County, Michigan. Theoretically, low AQUIPRO pollution potential scores
      should have more frequent occurrences of ground water contamination events than
      areas with high AQUIPRO scores with similar land-use, well construction, and well
      densities. The relative AQUIPRO scores were compared with the frequency of
      occurrences of nitrate-N in ground water wells. The average nitrate-N
      concentrations within each relative AQUIPRO vulnerability scores category were
      also compared. The results indicate that domestic wells containing 5 mg/L or more
      nitrate-N showed a positive correlation between the frequency of occurrences of
      nitrate-N and relative decrease of AQUIPRO (r2 = 0.99) vulnerability scores. In
      other words, as the ground water pollution potential increases, the occurrence
      frequency of nitrate-N also increases. Furthermore, the results show that as the
      relative AQUIPRO (r2 = 0.96) vulnerability scores decrease, the mean nitrate-N
      concentrations also increase.

PMID- 14649858
TI  - Behavior of gasoline pools following a denatured ethanol spill.
AB  - In 1999, approximately 72 m3 of denatured fuel-grade ethanol spilled at a bulk
      fuel terminal that had existing contamination within the subsurface. An
      unanticipated increase in the measured depth of the light nonaqueous phase liquid
      (LNAPL) was observed in nearby monitoring wells following the spill. This paper
      presents results of a laboratory analysis designed to understand the apparent
      increase in LNAPL mobility at this site. The two-dimensional stainless steel and
      glass tank allowed visual assessment of the potential effects that the addition
      of denatured ethanol may have on a site with pre-existing gasoline contamination.
      Digital images of gasoline and ethanol spill experiments were analyzed for
      changes in the characteristics of the existing gasoline pool and residual
      gasoline saturation in the unsaturated zone. Reductions in the surface and
      interfacial tensions resulted in significant changes in the size, shape, and
      saturation of the gasoline pool after the addition of ethanol to the system. The
      final gasoline pool occupied a smaller area and had a higher saturation. In
      addition, some smearing of the gasoline into the saturated zone occurred as the
      capillary fringe was depressed.

PMID- 14649859
TI  - Simulation of submarine ground water discharge to a marine estuary: Biscayne Bay,
      Florida.
AB  - Variable density ground water flow models are rarely used to estimate submarine
      ground water discharge because of limitations in computer speed, data
      availability, and availability of a simulation tool that can minimize numerical
      dispersion. This paper presents an application of the SEAWAT code, which is a
      combined version of MODFLOW and MT3D, to estimate rates of submarine ground water
      discharge to a coastal marine estuary. Discharge rates were estimated for
      Biscayne Bay, Florida, for the period from January 1989 to September 1998 using a
      three-dimensional, variable density ground water flow and transport model.
      Hydrologic stresses in the 10-layer model include recharge, evapotranspiration,
      ground water withdrawals from municipal wellfields, interactions with surface
      water (canals in urban areas and wetlands in the Everglades), boundary fluxes,
      and submarine ground water discharge to Biscayne Bay. The model was calibrated by
      matching ground water levels in monitoring wells, baseflow to canals, and the
      position of the 1995 salt water intrusion line. Results suggest that fresh
      submarine ground water discharge to Biscayne Bay may have exceeded surface water
      discharge during the 1989, 1990, and 1991 dry seasons, but the average discharge
      for the entire simulation period was only approximately 10% of the surface water
      discharge to the bay. Results from the model also suggest that tidal canals
      intercept fresh ground water that might otherwise have discharged directly to
      Biscayne Bay. This application demonstrates that regional scale variable density
      models are potentially useful tools for estimating rates of submarine ground
      water discharge.

PMID- 14649860
TI  - Monitoring well interception with fractures in clayey till.
AB  - When using monitoring wells for investigation of contaminant sources in clayey
      till, there is a high risk that fractures may cause mobile contaminants to bypass
      the monitoring wells. This paper indicates that the probability of interception
      between monitoring wells and hydraulic conductive fractures is often
      significantly less than 50%. Based on a field experiment and application of a
      calibrated discrete fracture matrix diffusion numerical model (FRAC3Dvs), the
      paper also evaluates pesticide-monitoring results for different positions of
      monitoring well screen relative to fractures. For well screens situated 0.25 and
      2 m from a conductive fracture, the first concentrations of the pesticide
      metabolite (2,6 dichlorobenzamide, "BAM") would be measured two years and 18
      years, respectively, after the contaminant had been transported into an
      underlying aquifer. In this way, underlying aquifers may be subjected to
      contamination by downward moving contamination without being observed in
      monitoring wells in the till.

PMID- 14649861
TI  - Long-term disturbance of ground water chemistry following well installation.
AB  - Ground water samples collected from a multilevel sampler shortly after its
      construction showed significantly higher alkalinity and concentrations of calcium
      and magnesium than those from nearby wells installed 10 years earlier. The
      sampler was drilled using a conventional hollow-stem power auger in a sandy,
      silicate aquifer lying beneath an isthmus between two lakes in northern
      Wisconsin. Ground water in the study area is of low ionic strength and its
      chemistry is dominated by silicate mineral weathering. Periodic sampling over two
      years following installation of the sampler showed that the higher solute
      concentrations had subsequently decreased. Oxygen isotope signature and other
      solute species, such as sulfate and chloride, were comparable to those of older
      wells and did not show any notable trends over time. Independent variation of
      other chemical species that cannot be derived from aquifer minerals, and the
      similarly high concentrations in older wells shortly after their installation,
      suggest that rapid dissolution of fresh mineral surfaces and hyperfine particles
      generated during drilling has induced the enhanced concentrations. This
      observation is consistent with the field equivalent of laboratory mineral
      dissolution experiments that show initially increased dissolution rates that
      decay over time. Well installations for geochemical sampling in dominantly
      silicate material may require longer times to reach an equilibrium state than has
      been previously thought.

PMID- 14649862
TI  - Deep water circulation, residence time, and chemistry in a karst complex.
AB  - We investigated the hydrochemistry of a complex karst hydrosystem made of two
      carbonate units along a coastal lagoon. Ground water emerges on the lagoon floor
      from a submarine spring. In addition, thermal waters circulate through the
      limestone and mix with karst water near the lagoon shore. A distinction between
      the water from the two carbonate units is related to marine influences and human
      activities. In one of the massifs, the data show an incongruent dissolution of
      dolomite with time. In the other system, a slight contamination by saline fluids
      from the thermal reservoir has led to high calcium and magnesium concentrations.
      36Cl, 14C, and 3H data constrain the residence time of the water, and allow for
      the distinguishing of four circulation types: (1) shallow surface circulation
      (primarily above sea level) in the karstic units with short residence times (<20
      years); (2) shallow subsurface circulation (approximately 0 to -50 m) below the
      karstic units with residence time in the order of 50 years; (3) deep circulation
      at depth of 700 to 1500 m in the Jurassic limestones below thick sedimentary
      cover, with residence time of several thousand years for a part of the water; and
      (4) deep circulation at a depth of approximately 2500 m, which represents the
      thermal reservoir in the Jurassic units with residence time of approximately
      100,000 years. An interpretative hydrogeological framework is based on the
      constraints of the geochemical analyses of the deep thermal system, and by water
      flow from the surface to the deep parts of the carbonate formations.

PMID- 14649863
TI  - Contaminant transport in fractured chalk: laboratory and field experiments.
AB  - Laboratory experiments were performed on chalk samples from Denmark and Israel to
      determine diffusion and distribution coefficients. Batch tests were used to
      define sorption isotherms for naphthalene and o-xylene. Linear sorption isotherms
      were observed and described with Henry-isotherms. Because of the high purity and
      low contents of clay minerals and organic carbon, Danish and white Israeli chalk
      generally have low retardation capacities. Contrarily, gray Israeli chalk, with
      organic carbon fractions as high as 1.092%, remarkably retards organic
      contaminants. The K(OC) concept is not applicable to predicting distribution
      coefficients based on the organic carbon content in the chalk samples. Effective
      diffusivities of o-xylene, naphthalene, and several artificial tracers were
      determined using through-diffusion experiments. Based on measured diffusion
      coefficients and available literature values, a chalk specific exponent of 2.36
      for Archie's law was derived, allowing a satisfactory estimate of relative
      diffusivities in chalk. A field-scale tracer test with uranine and lithium was
      performed in the Negev desert (Israel) to examine the transferability of
      diffusivities determined on small rock samples in the laboratory. Due to low
      recovery rates of the tracer, a modified single fissure dispersion model was used
      for inverse modeling of the breakthrough curves. Resulting diffusivities deviate
      insignificantly from the laboratory values, which are considered to be
      representative for the investigated part of the aquifer and applicable in
      transport models.

PMID- 14649864
TI  - A modular injection system, multilevel sampler, and manifold for tracer tests.
AB  - Ground water injection and sampling systems were developed for bacterial
      transport experiments in both homogenous and heterogeneous unconsolidated,
      surficial aquifers. Two types of injection systems, a large single tank and a
      dynamic mixing tank, were designed to deliver more than 800 L of amended ground
      water to the aquifer over 12 hours, without altering the ground water
      temperature, pH, Eh, or dissolved gas composition. Two types of multilevel
      samplers (MLSs) were designed and installed. Permanent MLSs performed well for
      the homogenous surficial aquifer, but their installation procedure promoted
      vertical mixing, which could obfuscate experimental data obtained from vertically
      stratified, heterogeneous aquifers. A novel, removable MLS was designed to fit in
      2- and 4-inch wells. Expandable O-rings between each sampling port hydraulically
      isolated each port for sample collection when a nut was tightened at the land
      surface. A low-cost vacuum manifold system designed to work with both MLS designs
      used 50 mL centrifuge tubes to efficiently sample 12 MLS ports with one
      peristaltic pump head. The integrated system was developed and used during four
      field campaigns over a period of three years. During each campaign, more than
      3000 ground water samples were collected in less than one week. This system
      should prove particularly useful for ground water tracer, injection, and push
      pull experiments that require high-frequency and/or high-density sampling.

PMID- 14649865
TI  - Ground water quality assessment using multi-rectangular diagrams.
AB  - A new graphical technique is proposed here for classifying chemical analyses of
      ground water. In this technique, a diagram is constructed using rectangular
      coordinates. The new diagram, called a multi-rectangular diagram (MRD), uses
      adjacent multi-rectangles in which each rectangle represents a specific ground
      water type. This new diagram has the capability to accommodate a large number of
      data sets. MRDs have been used to classify chemical analyses of ground water in
      the Chaj Doab area of Pakistan to illustrate this new approach. Using this
      graphical method, the differentiated ground water types are calcium bicarbonate,
      magnesium bicarbonate, sodium bicarbonate, and sodium sulfate. Sodium bicarbonate
      emerges as the most abundant ground water type. MRDs also offer a visual display
      of the Chebotarev sequence of ground water quality evolution.

PMID- 14649866
TI  - Steady flow to a well near a stream with a leaky bed.
AB  - We present an explicit analytic solution for steady, two-dimensional ground water
      flow to a well near a leaky streambed that penetrates the aquifer partially.
      Leakage from the stream is approximated as occurring along the centerline of the
      stream. The problem domain is infinite and pumping on one side of the stream
      induces flow on the other side. The solution includes the effects of uniform flow
      in the far field and a sloping hydraulic head in the stream. We use the solution
      to investigate the interaction between ground water and surface water in the
      stream, the effects of pumping on the opposite side of the stream, and the
      effects of the leaky streambed on the capture zone envelope of the well. We
      develop a relationship between parameters such that the pumping well will not
      capture water from the stream, or from the opposite side of the stream. When the
      discharge of the well is large enough to capture water from the stream, the shape
      of the capture zone envelope depends on flow conditions on the side of the stream
      opposite the well.

PMID- 14649867
TI  - Dip and anisotropy effects on flow using a vertically skewed model grid.
AB  - Darcy flow equations relating vertical and bedding-parallel flow to vertical and
      bedding-parallel gradient components are derived for a skewed Cartesian grid in a
      vertical plane, correcting for structural dip given the principal hydraulic
      conductivities in bedding-parallel and bedding-orthogonal directions. Incorrect
      minus-correct flow error results are presented for ranges of structural dip (0 <
      or = theta < or = 90) and gradient directions (0 < or = phi < or = 360). The
      equations can be coded into ground water models (e.g., MODFLOW) that can use a
      skewed Cartesian coordinate system to simulate flow in structural terrain with
      deformed bedding planes. Models modified with these equations will require input
      arrays of strike and dip, and a solver that can handle off-diagonal hydraulic
      conductivity terms.

PMID- 14649868
TI  - Lithium isotope geochemistry and origin of Canadian shield brines.
AB  - Hypersaline calcium/chloride shield brines are ubiquitous in Canada and areas of
      northern Europe. The major questions relating to these fluids are the origin of
      the solutes and the concentration mechanism that led to their extreme salinity.
      Many chemical and isotopic tracers are used to solve these questions. For
      example, lithium isotope systematics have been used recently to support a marine
      origin for the Yellowknife shield brine (Northwest Territories). While having
      important chemical similarities to the Yellowknife brine, shield brines from the
      Sudbury/Elliot Lake (Ontario) and Thompson/Snow Lake (Manitoba) regions, which
      are the focus of this study, exhibit contrasting lithium behavior. Brine from the
      Sudbury Victor mine has lithium concentrations that closely follow the sea water
      lithium-bromine concentration trajectory, as well as delta6Li values of
      approximately -28/1000. This indicates that the lithium in this brine is
      predominantly marine in origin with a relatively minor component of crustal
      lithium leached from the host rocks. In contrast, the Thompson/Snow Lake brine
      has anomalously low lithium concentrations, indicating that it has largely been
      removed from solution by alteration minerals. Furthermore, brine and nonbrine
      mine waters at the Thompson mine have large delta6Li variations of approximately
      30/1000, which primarily reflects mixing between deep brine with delta6Li of -35
      +/- 2/1000 and near surface mine water that has derived higher delta6Li values
      through interactions with their host rocks. The contrary behavior of lithium in
      these two brines shows that, in systems where it has behaved conservatively,
      lithium isotopes can distinguish brines derived from marine sources.

PMID- 14649869
TI  - Geophysical expression of natural recharge in different geological terrains.
AB  - Behavior of the Dar-Zarrouk parameters--longitudinal unit conductance, transverse
      unit resistance, longitudinal resistivity, and transverse resistivity--has been
      compared with the behavior of the natural recharge in two geological terrains.
      Contour patterns of the geophysical parameters and those of natural recharge have
      been analyzed and a qualitative relation in their behavior was recognized.
      Graphical comparison of the geophysical and hydrogeological parameters clearly
      illustrates a qualitative relationship between the two parameters. Use of such
      qualitative relation in the field of ground water exploration and management
      studies is explained. A modest beginning is attempted to arrive at a quantitative
      relation between natural recharge and Dar-Zarrouk parameters.

PMID- 14649870
TI  - A simple constant-head injection test for streambed hydraulic conductivity
      estimation.
AB  - A fast, efficient constant-head injection test (CHIT) for in situ estimation of
      hydraulic conductivity (K) of sandy streambeds is presented. This test uses
      constant-head hydraulic injection through a manually driven piezometer. Results
      from CHIT compare favorably to estimates from slug testing and grain-size
      analysis. The CHIT combines simplicity of field performance, data interpretation,
      and accuracy of K estimation in flowing streams.

PMID- 14649871
TI  - Autobiographical note: Stanley N. Davis.

PMID- 14649872
TI  - The effect of thyroid hormones on blood insulin level and metabolic parameters in
      diabetic rats.
AB  - The effect of exogenous thyroid hormones on blood insulin and metabolic
      parameters in diabetic rats was investigated. Three groups of rats were treated
      with streptozotocin (STZ; 50 mg/kg b.w., intravenously) and one group receiving
      only saline served as control. Beginning with the third day after STZ treatment,
      until the last day before decapitation, i.e. for 11 days, two groups of diabetic
      rats were treated with T3 (50 microg/kg b.w., i.p.) or T4 (250 microg/kg b.w.,
      i.p.). After two weeks, STZ injected rats had lower body weight, hyperglycemia
      with a simultaneous drop in blood insulin and decrease of T3 and T4
      concentrations in comparison to control animals. Liver glycogen content was also
      reduced, whereas serum lactate, free fatty acids, triglycerides and cholesterol
      were elevated. Exogenous thyroid hormones given to diabetic rats substantially
      attenuated hyperglycemia without any significant changes in blood insulin
      concentration. An additional reduction of body weight gain and depletion in liver
      glycogen stores were also observed. Thyroid hormones augmented serum lactate and
      cholesterol and had no beneficial effect on elevated free fatty acids and
      triglycerides. It can be concluded that in spite of partial restriction of
      hyperglycemia, thyroid hormones evoked several unfavourable changes strongly
      limiting their potential use in diabetes.

PMID- 14649873
TI  - Catecholamine responses to high intensity cycle ergometer exercise: body mass or
      body composition?
AB  - The purpose of this study was to compare the sympathoadrenergic and metabolic
      responses following 30 s of maximal high intensity cycle ergometry exercise when
      cradle resistive forces were derived from total-body mass (TBM) or fat-free mass
      (FFM). Increases in peak power output (PPO) and pedal velocity were recorded when
      resistive forces reflected FFM (953 +/- 114 W vs 1020 +/- 134 W; 134 +/- 8 rpm vs
      141 +/- 7 rpm ; P < 0.05). No differences were observed between mean power output
      (MPO), fatigue index (FI%), work done (WD) or heart rate (HR) when the TBM and
      FFM protocols were compared. There were no differences between the TBM and FFM
      protocols for adrenaline (A), noradrenaline (NA) or blood lactate concentrations
      ([La-]B) recorded at rest, immediately post or 24 h post exercise. However,
      increases in blood concentrations of A and NA (P < 0.05) were recorded for both
      the TBM and FFM protocol immediately post exercise. Significant correlations (P <
      0.05) were recorded between PPOs, immediate post- exercise NA and [La-]B for both
      the TBM and FFM protocols. [La-]B levels were also significantly elevated (P <
      0.01) immediately post exercise for both the TBM and FFM protocols. The results
      from this study suggest that greater peak power outputs are obtainable with no
      subsequent differences in neurophysiological or metabolic stress as determined by
      plasma A, NA and [La-]B concentrations when resistive forces reflect FFM and not
      TBM during loading procedures. The findings also indicate that immediate post
      exercise concentrations return to resting levels 24 h post exercise.

PMID- 14649874
TI  - Influence of the fatty acid composition of lipids in chylomicron remnants derived
      from fish or corn oil on the lipid profile of cultured rat hepatocytes.
AB  - The aim of this work was to characterise the lipid and fatty acid composition of
      chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (PUFA)
      and to investigate their influence on the fatty acid profiles of the lipids of
      rat hepatocytes cultured in monolayers. Chylomicrons were prepared from the lymph
      collected from the thoracic duct of rats given an oral dose of fish or corn oil
      (high in n-3 and n-6 PUFA, respectively), and remnants were prepared in vitro
      from such chylomicrons using rat plasma containing lipoprotein lipase. The fatty
      acids predominating in the oils abounded also in their respective chylomicrons
      and remnants, especially in triacylglycerols. Chylomicrons as well as remnants
      contained small amounts of phospholipids and long-chain PUFA that were minor in,
      or absent from, the dietary oils, evidently provided by the intestinal
      epithelium. The incubation of hepatocytes for 6 h, with either n-3 or n-6 PUFA
      rich remnants (0.25-0.75 mM triacylglycerol) resulted in a dose-dependent
      increase in the amount of triacylglycerols and phospholipids in the cells, which
      was not affected further by increasing the incubation time to 19 h. Whereas
      hepatocyte triacylglycerols mostly incorporated the PUFA predominating in each
      remnant type, the fatty acid profile of cell phospholipids was virtually
      unchanged. In addition, irrespective of whether they were enriched in n-3 or n-6
      PUFA, remnants promoted a relative decrease in the amount of cholesteryl esters,
      a minor hepatocyte lipid class poor in PUFA. The results demonstrate that the
      hepatocyte fatty acid profile is modulated in a lipid-class specific way by the
      amount and type of dietary PUFA delivered to cells in chylomicron remnants.

PMID- 14649875
TI  - Influence of fasting status on the effects of coconut oil on chick plasma and
      lipoprotein composition.
AB  - For a better understanding of the hyperlipidemic function of saturated fat, we
      have studied the effects of diet supplementation with 10-20% coconut oil on the
      chick plasma and lipoprotein composition under postprandial and starvation
      conditions. A significant hypercholesterolemia was found in chicks fed the
      standard diet after 12 h of food deprivation. In these conditions, LDL
      cholesterol also increased, whereas triglyceride levels were reduced in HDL, VLDL
      and chylomicron fractions. Coconut oil induced a significant hypercholesterolemia
      under both conditions, also increasing the plasma triglyceride content under
      postprandial conditions, but not after starvation. Coconut oil feeding increased
      all the chemical components of HDL, especially under postprandial conditions, but
      did not affect the HDL-triglycerides under food-deprivation conditions. Total
      cholesterol and triglyceride levels in LDL increased after coconut oil
      supplementation to the diet. Differences were more pronounced under postprandial
      conditions. Changes in VLDL and chylomicron composition were less evident.

PMID- 14649876
TI  - Beneficial effect of goat milk on bioavailability of copper, zinc and selenium in
      rats.
AB  - We studied the effects of dietary inclusion of freeze-dried goat and cow milk on
      the utilization of copper, zinc and selenium, and on the metabolic fate of copper
      and zinc, in rats using a standard (non-milk) control diet recommended by the
      American Institute of Nutrition and diets based on goat or cow milk. For animals
      given the goat milk diet, the apparent digestibility coefficient (ADC) of copper
      is similar to that obtained with the standard diet and higher than that in
      animals given the cow milk diet. The copper balance was higher among the rats
      given the goat milk and the standard diets than among those given cow milk. The
      ADC and retention of zinc and selenium were higher for the goat milk diet than
      for the other two diets. The copper content in the kidneys and in the femur was
      greater when the animals consumed a goat milk diet than a cow milk diet. Zn
      deposits in femur, testes, liver, kidney, heart and longissimus dorsi muscle were
      greatest with the goat-milk diet, followed by the standard diet and were lowest
      for the rats given cow-milk diet. This study shows that the goat-milk has an
      important and beneficial effect on the bioavailability of copper, zinc and
      selenium.

PMID- 14649877
TI  - Functional expression of the short isoform of the murine leptin receptor Ob-Rc
      (muB1.219) in Xenopus laevis oocytes.
AB  - Leptin, a hormone mainly secreted by the adipose tissue, acts on the hypothalamus
      to regulate food intake and thermogenesis. Six leptin receptor isoforms have been
      identified and localized in different tissues. While it is clear that leptin
      action in the brain occurs by binding to the long receptor isoform, several
      studies have shown that the short isoforms could be involved in the transcellular
      transport of the hormone from the blood to the brain. Based on these works, we
      decided to investigate whether the murine short leptin receptor isoform Ob-Rc
      (muB1.219) could transport leptin when expressed in Xenopus laevis oocytes.
      MuB1.219 cRNA was injected into the oocytes and functional studies were performed
      by incubating the oocytes in the presence of 2.5 nM [125I]-leptin, under
      different conditions. Results showed that leptin binding to the injected oocytes
      was four to eight-fold higher than the binding to the non-injected oocytes. This
      was blocked by 250 nM of non-radiolabeled leptin, suggesting that the binding was
      specific. Leptin internalization was observed from 30 min incubation onwards.
      Coexpression of the human Na+/glucose cotransporter and the leptin receptor
      showed that leptin increased sugar uptake into the oocytes. These results
      demonstrate that the short leptin receptor Ob-Rc is able to mediate binding and
      internalization of the hormone when expressed in oocytes and that it may perform
      intracellular signaling.

PMID- 14649879
TI  - Effect of IGF-I on total serum antioxidant status in cirrhotic rats.

PMID- 14649880
TI  - Introduction to special issue: targeted toxins for glioma therapy.

PMID- 14649878
TI  - Mitochondrial control of neuron death and its role in neurodegenerative
      disorders.
AB  - Genetic or functional mitochondrial alterations can result in the initiation of
      cell death programs that are believed to contribute to cell death in diabetes,
      ageing and neurodegenerative disorders. Mitochondria are being considered the
      main link between cellular stress signals activated during acute and chronic
      nerve cell injury, and the execution of nerve cell death. This second function of
      mitochondria is regulated by several families of proteins that can trigger an
      increase in permeability of the outer and/or inner mitochondrial membrane. One
      example of this is the formation of the mitochondrial permeability transition
      pore (MPTP). This process can trigger the release of cell death-inducing factors
      from mitochondria, as well as a dissipation of the mitochondrial transmembrane
      potential, depletion of ATP, and increased free radical formation. Among the
      factors released from mitochondria are cytochrome c, the apoptosis inductor
      factor (AIF), and caspases. We review the role of the MPTP in diverse
      physiological and pathological processes, including neurodegenerative disorders
      such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral
      sclerosis (ALS). The design of drugs that could interfere with the functions of
      the MPTP could allow novel therapeutic approaches for the treatment of acute and
      chronic nerve cell injury.

PMID- 14649881
TI  - Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107) for therapy of
      malignant gliomas.
AB  - The authors review the preclinical and clinical results of the ligand-targeted
      toxin conjugate Transferrin-CRM107 (Tf-CRM107), for the treatment of malignant
      gliomas. Tf-CRM107 is a conjugate protein of diphtheria toxin with a point
      mutation (CRM107) linked by a thioester bond to human transferrin (Tf). This
      conjugate exhibits potent cytotoxicity in vitro against mammalian cells
      expressing the transferrin receptor with activity at picomolar concentrations.
      Phase I clinical trial results demonstrated that Tf-CRM107, delivered via a high
      flow convection method utilizing stereotactically placed catheters, produced
      tumor response in patients with malignant brain tumors refractory to conventional
      therapy without severe neurologic or systemic toxicity. The results of a Phase II
      study are also summarized. Tf-CRM107 treatment results in complete and partial
      tumor response without severe toxicity in 35% of the evaluable patients. These
      data warrant a Phase III study as well as continued research in the field of
      targeted toxin therapy. Future directions of research include optimizing Tf
      CRM107 delivery to targeted brain regions, and improving the treatment efficacy
      by combining with other toxin conjugates targeted to different receptors.

PMID- 14649882
TI  - Interleukin-4-Pseudomonas exotoxin chimeric fusion protein for malignant glioma
      therapy.
AB  - Human malignant glioma cell lines, primary cell cultures, and tumor specimens
      derived from surgical samples have been shown to overexpress high-affinity
      receptors (R) for interleukin-4 (IL-4) in vitro and in situ. The significance of
      IL-4R expression on malignant glioma cells is still unclear. However, IL-4 has
      been reported to mediate functional effects in several solid tumor cell lines.
      These activities include inhibition of cell proliferation, regulation of adhesion
      molecules, and induction of signal transduction through the JAK/STAT pathway. To
      target IL-4Rs on tumor cells, we have produced a chimeric recombinant fusion
      protein consisting of a binding ligand, circularly permuted IL-4 and a mutated
      form of Pseudomonas exotoxin. This molecule is termed IL4(38-37)-PE38KDEL, cpIL4
      PE, or IL-4 cytotoxin. Recombinant cpIL4-PE is highly and specifically cytotoxic
      to glioma cell lines in vitro, while it is not cytotoxic or less cytotoxic to
      hematopoietic and normal brain cells. In a nude mouse model, cpIL4-PE showed
      significant antitumor activity and partial or complete regression of small or
      large established human glioblastoma tumors. Encouraging preclinical efficacy,
      safety, and tolerability studies lead to testing of this agent in patients with
      recurrent glioblastoma. Based on these pilot studies, an extended Phase I/II
      clinical trial is currently ongoing to determine safety, tolerability, and
      efficacy of cpIL4-PE when injected stereotactically directly into the recurrent
      glioma by convection enhanced delivery. Preliminary clinical results suggest that
      cpIL4-PE can cause pronounced necrosis of recurrent glioma tumors without
      systemic toxicity. The central nervous system toxicities observed were attributed
      to the volume of infusion and/or nonspecific toxicity. Ongoing clinical trials
      will reveal antitumor activities of IL-4 cytotoxin in recurrent malignant glioma.

PMID- 14649883
TI  - Progress report of a Phase I study of the intracerebral microinfusion of a
      recombinant chimeric protein composed of transforming growth factor (TGF)-alpha
      and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the
      treatment of malignant brain tumors.
AB  - TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding
      ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin,
      PE-38. After in vitro and in vivo animal studies that showed specific activity
      and defined the maximum tolerated dose (MTD), we investigated this agent in a
      Phase I trial. The primary objective of this study was to define the MTD and dose
      limiting toxicity of TP-38 delivered by convection-enhanced delivery in patients
      with recurrent malignant brain tumors. Twenty patients were enrolled in the study
      and doses were escalated from 25 ng/mL to 100 with a 40 mL infusion volume
      delivered by two catheters. One patient developed Grade IV fatigue at the 100
      ng/mL dose, but the MTD has not been established. The overall median survival
      after TP-38 for all patients was 23 weeks whereas for those without radiographic
      evidence of residual disease at the time of therapy, the median survival was 31.9
      weeks. Overall, 3 of 15 patients, with residual disease at the time of therapy,
      have demonstrated radiographic responses and one patient with a complete response
      and has survived greater than 83 weeks.

PMID- 14649884
TI  - Interleukin-13 receptor-directed cytotoxin for malignant glioma therapy: from
      bench to bedside.
AB  - Central nervous system malignant neoplasias, in particular, glioblastoma
      multiforme (GBM) have defied all current therapeutic modalities. New therapies
      involving tumor targeting approach are being explored. This approach relies on
      the identification of unique or over-expressed cell surface receptors or antigens
      on tumor cells. In that regard, we have identified receptor for an immune
      regulatory cytokine, interleukin-13 (IL-13), which is over-expressed on human
      malignant glioma cell lines and primary tumor cell cultures. To target IL-13
      receptors (IL-13R) for cancer therapy, we have developed a recombinant fusion
      protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13
      PE38QQR or IL-13 cytotoxin). The IL-13 cytotoxin was found to be highly selective
      and potent in killing human GBM cells in vitro while normal cells including
      immune cells, endothelial cells and normal brain cells were generally spared the
      cytotoxic effect of IL-13 cytotoxin. This is because these cells either expressed
      none or expressed low levels of IL-13R. Consistent with in vitro cytotoxic
      activity, IL-13 cytotoxin mediated remarkable anti-tumor activity to human glioma
      in animal xenograft models. The direct injection of IL-13 cytotoxin into
      subcutaneous human GBM tumors grown in nude mice produced complete and durable
      regression of established tumors. Intravenous and intraperitoneal administration
      of IL-13 cytotoxin also reduced tumor burden significantly with fewer complete
      responders. All animals tolerated therapy well with minimal toxicity to vital
      organs. Pre-clinical safety and toxicity studies were performed in mice, rats and
      monkeys. Systemic administration of IL-13 cytotoxin appeared to be well tolerated
      at high doses (up to 50 microg/kg). Intrabrain parenchyma administration of IL-13
      cytotoxin at doses up to 100 microg/ml was very well tolerated without any
      evidence of gross or microscopic necrosis, whereas at 500 microg/ml dose,
      localized necrosis was observed in normal rat brain. Based on these encouraging
      pre-clinical studies, three Phase I/II clinical trials in adults with malignant
      glioma have been initiated. The first clinical trial involves convection-enhanced
      delivery (CED) of IL-13 cytotoxin into recurrent malignant glioma. This route of
      IL-13 cytotoxin administration appears to be fairly well tolerated with no
      neurotoxicity. The second clinical trial involves infusion of IL-13 cytotoxin by
      CED following tumor resection. The initial stage of the second study assessed
      histologic effect of drug administered prior to resection. In third one, IL-13
      cytotoxin is infused by CED followed by tumor resection. All three clinical
      trials are currently ongoing.

PMID- 14649885
TI  - BR96-DOX immunoconjugate targeting of chemotherapy in brain tumor models.
AB  - An immunoconjugate of doxorubicin (adriamycin) and a tumor-specific monoclonal
      antibody, BR96-DOX (now SGN-15) targets chemotherapy to cells that express the
      LewisY antigen. This immunoconjugate is internalized into lysosomes in antigen
      expressing cells, with release of free doxorubicin after hydrolysis of the acid
      labile linker. We review our studies using BR96-DOX in a human small-cell lung
      carcinoma intracerebral xenograft model in nude rats. We have found that the
      immunoconjugate is effective against intracerebral tumors when delivery is
      enhanced with osmotic disruption of the blood-brain barrier (BBB). Enhanced
      delivery of BR96-DOX with BBB opening can work together with radiotherapy to
      increase antitumor efficacy, which is maximally effective if immunoconjugate is
      administered prior to radiotherapy. In heterogeneous brain tumors, enhanced
      delivery of BR96-DOX significantly reduced tumor volumes, but local release of
      doxorubicin by targeting antigen expressing cells shows modest cytotoxicity
      against adjacent non-expressor cells. Although BR96-DOX is not effective against
      glioma cells tested, it does provide a model for drug-immunoconjugate therapy of
      gliomas. Our studies in a rat brain tumor model point out the importance of
      optimized delivery, antigenic heterogeneity, and bystander effect for brain tumor
      therapy. We review additional studies of drug-mAb immunoconjugates pertinent to
      the treatment of gliomas.

PMID- 14649888
TI  - The Dyson Perrins Laboratory at Oxford.

PMID- 14649889
TI  - Synthesis and properties of hetero-halogenated TTFs.
AB  - Novel hetero-halogenated TTFs containing both chlorine and iodine atoms were
      prepared and their unique characters based on the halogen atoms were examined.

PMID- 14649887
TI  - Combination fusion protein therapy of refractory brain tumors: demonstration of
      efficacy in cell culture.
AB  - Primary brain tumors including anaplastic astrocytomas and glioblastoma
      multiforme are difficult to treat because of their locally invasive nature and
      relative resistance to chemotherapy and radiation therapy. Novel agents that can
      kill multi-drug resistant tumor cells and reach tumor cells at distant sites in
      the brain are needed. One such class of agents is fusion proteins which consist
      of brain-tumor-selective peptide ligands fused to peptide toxins. The ligand
      directs the protein to the glioma cell surface; the peptide toxin is then
      internalized into the cell, translocates to the cytosol and catalytically
      inactivates protein synthesis leading to cell death. Fusion proteins are toxic to
      multi-drug resistant brain tumor cells. Because of the large molecular weight of
      these molecules, a unique delivery system has been developed--convection-enhanced
      delivery (CED). The method creates a bulk flow which supplements diffusion and
      achieves drug concentrations in the brain parenchyma orders of magnitude greater
      than by systemic administration. Patients with recurrent glioma treated with
      individual fusion protein CED have obtained clinical remissions lasting years.
      However, toxicities to normal brain have been observed and relapses ultimately
      occurred. To address the clinical need of these patients and improve upon the
      therapeutic index observed to date with single fusion protein CED, we generated a
      novel fusion protein DAB389EGF and tested it in combination with another active
      fusion protein, IL13PE38QQR. We observed potent glioma cytotoxicity with each
      fusion protein and synergistic toxicity with the combination. Further, brain
      tumor cells showed heterogeneous expression of individual receptors suggesting
      that the combination--DAB389EGF and IL13PE38QQR may show improved efficacy and
      should undergo further preclinical development for therapy of patients with
      relapsed high-grade gliomas.

PMID- 14649886
TI  - Targeting the over-expressed urokinase-type plasminogen activator receptor on
      glioblastoma multiforme.
AB  - A recombinant fusion protein targeting the urokinase-type plasminogen activator
      receptor (uPAR) and delivering a potent catalytic toxin has the advantage of
      simultaneously targeting both over-expressed uPAR on glioblastoma cells and on
      the tumor neovasculature. Such a hybrid protein was synthesized consisting of the
      noninternalizing amino-terminal fragment (ATF) of urokinase-type plasminogen
      activator (uPA) for binding, and the catalytic portion of diphtheria toxin (DT)
      for killing, and the translocation enhancing region (TER) of DT for
      internalization. The protein was highly selective for human glioblastoma in vitro
      and in vivo. In vivo, this DT/ATF hybrid called DTAT caused the regression of
      small subcutaneous uPAR-expressing tumors with minimal toxicity to critical
      organs. In vitro, DTAT killed only uPAR-positive glioblastoma cell lines and
      human endothelial cells in the form of the HUVEC cell line. Killing was selective
      and blockable with specific antibody. DTAT was highly effective against tumor
      cells cultured from glioblastoma multiforme patients and in vitro mixing
      experiments combining DTAT with DTIL13 another highly effective anti-glioblastoma
      agent showed that the mixture was as toxic as the most potent immunotoxin. In
      this article, we review our progress to date with DTAT.

PMID- 14649890
TI  - Enhanced 13C resolution in semi-selective HMbC: a band-selective, constant-time
      HMBC for complex organic structure elucidation by NMR.
AB  - A semi-selective 2D HMBC experiment is described which yields high-resolution in
      the indirect carbon-13 dimension by suppressing homonuclear proton coupling
      modulations and so provides an NMR technique suitable for the structure
      elucidation of organic compounds which exhibit particularly crowded carbon-13
      spectra.

PMID- 14649891
TI  - Stereospecificity in the silicon tethered alpha-(methyl)allylation of aldehydes.
AB  - Heating E- and Z-crotyl(diphenyl)silyloxy aldehydes, in the absence of an added
      catalyst, results in stereospecific intramolecular allyl transfer with moderate
      to high stereoselectivity.

PMID- 14649892
TI  - Synthesis and crystal structure of a meso-trialkynyl[28]hexaphyrin.
AB  - A 5,15,25-trialkynyl [28]hexaphyrin(1.1.1.1.1.1) is the main product of the boron
      trifluoride-catalysed condensation of meso-anthryl dipyrromethane and
      triisopropylsilylpropynal; it absorbs strongly in the near-infrared, out to 1093
      nm.

PMID- 14649893
TI  - Glycosyl phenylthiosulfonates (glyco-PTS): novel reagents for glycoprotein
      synthesis.
AB  - Controlled site-selective glycosylation can be achieved by combining site
      directed cysteine mutagenesis with chemical modification of the introduced thiol;
      a new class of more efficient chemoselective reagents, glycosyl
      phenylthiosulfonates, allow rapid glycosylations of representative simple thiols,
      peptides and proteins.

PMID- 14649894
TI  - Non-denaturing electrospray ionisation-mass spectrometry reveals ligand
      selectivity in histamine-binding protein RaHBP2.
AB  - ESI-MS has been used to probe the non-covalent interactions between a histamine
      binding protein, from Rhipicephalus appendiculatus, and a range of bioactive
      amine ligands.

PMID- 14649895
TI  - Bend ribbon-forming tetrahydrofuran amino acids.
AB  - Short oligomeric chains of C-glycosyl beta-D-arabinofuranose configured
      tetrahydrofuran amino acids (where the C-2 and C-5 substituents of the
      tetrahydrofuran ring are cis to each other) exhibit a well-defined repeating turn
      secondary structure stabilised by (i, i - 2) inter-residue hydrogen bonds. This
      is in contrast to the epimeric alpha-D-arabinofuranose oligomer (where the C-2
      and C-5 substituents of the tetrahydrofuran ring are trans to each other) in
      which there is no indication of any secondary structure in solution.

PMID- 14649896
TI  - Synthesis of potent CXCR4 inhibitors possessing low cytotoxicity and improved
      biostability based on T140 derivatives.
AB  - A peptidic CXCR4 antagonist T140 efficiently blocks the entry of T cell line
      tropic strains of HIV-1 (X4-HIV-1) into target cells. In this study, a series of
      T140 derivatives, replacing the basic amino acid residues with Glu (D-Glu) and/or
      L-citrulline (Cit), were synthesized in order to reduce non-specific binding and
      cytotoxicity. Among them, TE14011 ([Cit6, D-Glu8]-T140 with the C-terminal amide)
      exhibited strong anti-HIV activity and low cytotoxicity. TE14011 was found to be
      stable in mouse serum, but unstable in rat liver homogenate due to the deletion
      of the N-terminal Arg1-Arg2-L-3-(2-naphthyl)alanine (Nal)3 residues from the
      parent peptide. N-Terminal acetylation of TE14011 led to the development of a
      novel lead compound, Ac-TE 14011, which possesses a high selectivity index as
      well as increased stability in serum and liver homogenate.

PMID- 14649897
TI  - Enhancement of the T140-based pharmacophores leads to the development of more
      potent and bio-stable CXCR4 antagonists.
AB  - A CXCR4 antagonistic peptide, T140, and its bio-stable analogs, such as Ac
      TE14011, were previously developed. These peptides inhibit the entry of T cell
      line-tropic strains of HIV-1 (X4-HIV-1) into T cells. Herein, a series of TE14011
      analogs having modifications in the N-terminal region were synthesized to develop
      effective compounds with increased biostability. Among these analogs, 4F-benzoyl
      TE14011 (TF14013) showed the strongest anti-HIV activity derived from CXCR4
      antagonism, suggesting that a 4-fluorobenzoyl moiety at the N-terminus of T140
      analogs constitutes a novel T140-based pharmacophore for CXCR4 antagonists.
      Structure-activity relationship (SAR) studies on TE14011 analogs with N(alpha)
      acylation by several benzoic acid derivatives have disclosed a significant
      relationship between the anti-HIV activity and the Hammett constant (sigma) of
      substituted benzoic acids. TF14013 was found to be stable in mouse serum, but not
      completely stable in rat liver homogenate due to deletion of the C-terminal Arg14
      NH2 from the parent peptide. This biodegradation was completely suppressed by N
      alkyl-amidation at the C-terminus. Taken together, the enhancement of the T140
      based pharmacophores led to development of a novel CXCR4 antagonist, 4F-benzoyl
      TE14011-Me (TF14013-Me), which has very high anti-HIV activity and increased
      biostability.

PMID- 14649898
TI  - Biomimetic studies on polyenes.
AB  - The crispatenes and SNF4435 C&D are complex polypropionate derived natural
      products. The core structures of these compounds along with a complex unnatural
      structure can be easily prepared from a common polyene precursor simply by
      variation of the reaction conditions. The reaction pathways provide insight into
      the biosynthesis of these complex natural products.

PMID- 14649899
TI  - An approach to the generation of simple analogues of the antitumour agent
      spicamycin.
AB  - The one-step glycosylation of arylamines in acidic medium is extended to adenine
      derivatives for the first time, providing a considerable improvement over
      existing reactions. This method is used to prepare some rhamnospicamycin
      analogues containing different base moieties. Results suggest that this novel
      approach will be applicable to a wide range of carbohydrates and arylamines,
      possibly leading to a combinatorial library of analogues of spicamycin for the
      better understanding of the modes of action of this antitumour antibiotic family.

PMID- 14649900
TI  - A novel method for the synthesis of 4'-thiopyrimidine nucleosides using
      hypervalent iodine compounds.
AB  - The coupling reactions of cyclic sulfides with a silylated pyrimidine nucleobase
      using a hypervalent iodine reagent were investigated. The reaction of silylated
      uracil with cyclic sulfide 12 using PhI=O gave the desired beta-anomer 14 in
      moderate yield. 4'-Thiouridine (22) was obtained by deprotection of 14.

PMID- 14649901
TI  - Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3
      methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3
      methylcyclopentene-1-carboxylate.
AB  - Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3
      methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with
      preferential addition of lithium dibenzylamide to the face of the cyclic
      alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of
      enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1
      carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10
      eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution
      of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl
      N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl
      (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1
      carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after
      purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis
      gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective
      epimerisation of tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha
      methylbenzylaminocyclopentane-1-carboxylate by treatment with KO'Bu in 'BuOH
      gives tert-butyl (1S,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha
      methylbenzylaminocyclopentane-1-carboxylate in quantitative yield and in > 98%
      de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving
      (1S,2S,3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.

PMID- 14649902
TI  - Asymmetric synthesis of anti-(2S,3S)- and syn-(2R,3S)-diaminobutanoic acid.
AB  - Conjugate addition of homochiral lithium N-benzyl-N-alpha-methylbenzylamide to
      tert-butyl (E)-cinnamate or tert-butyl (E)-crotonate and in situ amination with
      trisyl azide results in the exclusive formation of the corresponding 2-diazo-3
      amino esters in > 95% de. Amination of the lithium (E)-enolates of tert-butyl
      (3S,alphaR)-3-N-benzyl-N-alpha-methylbenzylamino-3-phenylpropanoate or tert-butyl
      (3S,alphaS)-3-N-benzyl-N-alpha-methylbenzylaminobutanoate with trisyl azide gives
      the (2R,3R,alphaR)- and (2S,3S,alphaS )-anti-2-azido-3-amino esters in good
      yields and in 85% de and > 95% de respectively. Alternatively, tert-butyl anti
      (2S,3S,alphaS)-2-hydroxy-3-N-benzyl-N-alpha-methylbenzylaminobutanoate may be
      converted selectively to tert-butyl anti-(2S,3S,alphaS)-2-azido-3-N-benzyl-N
      alpha-methylbenzylaminobutanoate by aziridinium ion formation and regioselective
      opening with azide. Deprotection of tert-butyl (2S,3S,alphaS)-2-azido-3
      aminobutanoate via Staudinger reduction, hydrogenolysis and ester hydrolysis
      furnishes anti-(2S,3S)-diaminobutanoic acid in 98%, de and 98% ee. The asymmetric
      synthesis of the diastereomeric syn-(2R,3S)-diaminobutanoic acid (98% de and 98%
      ee) was accomplished via functional group manipulation of tert-butyl anti
      (2S,3S,alphaS)-2-hydroxy-3-N-benzyl-N-alpha-methylbenzylaminobutanoate in a
      protocol involving azide inversion of tert-butyl (2S,3S)-2-mesyloxy-3-N-Boc
      butanoate and subsequent deprotection.

PMID- 14649903
TI  - Synthetic studies towards the tunicamycins and analogues based on diazo
      chemistry. Total synthesis of tunicaminyl uracil.
AB  - A synthetic approach to the tunicamycins, a complex family of nucleosides with
      potent antibiotic and antiviral activities is reported based on diazo chemistry.
      The corresponding precursors for the synthesis of tunicaminyl uracil derivatives,
      the non-stabilized diazo derived from 13 and the aldehyde derivative of uridine,
      compound 4, were prepared efficiently from commercially available D-galactal and
      uridine, respectively. After a high yielding coupling reaction to obtain the
      ketone 14, a stereoselective reduction provided the corresponding tunicaminyl
      uracil derivative 17a and its C-7 epimer 17b. The interconversion of the diazo
      and aldehyde functional groups in the requisite building blocks was similarly
      achieved to obtain the ketone 32, which after reduction yielded the corresponding
      7-deoxy-6-hydroxy tunicaminyl uracil analogs 33a and 33b.

PMID- 14649904
TI  - A multicomponent coupling strategy suitable for the synthesis of the triene
      component of the oxazolomycin antibiotics.
AB  - Concise and versatile routes suitable for the synthesis of three geometric
      isomers of an analogue of the left hand triene sub-unit of oxazolomycin are
      reported. A strategy based upon a key Heck reaction was unsuccessful, and this
      was traced to a combination of steric encumbrance and electronic deactivation of
      the alkene substrate. An alternative Stille coupling strategy, however, proved to
      be both versatile and high yielding, and is potentially applicable to the
      synthesis of analogues with variation both in the side-chain geometry and in the
      identity of the terminal aromatic or heteroaromatic residue.

PMID- 14649905
TI  - Synthesis of hydroxymethyl branched [3.2.0]bicyclic nucleosides using a
      regioselective oxetane ring-formation.
AB  - Two [3.2.0]bicyclic nucleosides, 35 and 34, with one and two hydroxymethyl
      substituents, respectively, have been efficiently synthesized. A protected (3'-C
      vinyl-beta-D-allofuranosyl)thymine derivative 28 was easily prepared from
      diacetone-D-glucose and the thymine moiety was protected with a BOM-group. After
      the introduction of a leaving group in the 2'-position, the subsequent nucleoside
      31 was used as the substrate for a stereoselective dihydroxylation and a
      regioselective oxetane ring-formation to give after deprotection the bicyclic
      nucleoside 34. The surprisingly efficient formation of an oxetane was first
      discovered by serendipity on a corresponding methylfuranoside derivative. The
      allo-configured bicyclic nucleoside 34 was easily shortened to a ribo-configured
      analogue 35 by a diol-cleaving reaction and subsequent reduction. Both 34 and 35
      are conformationally restricted in the important intermediate 04'-endo
      conformation.

PMID- 14649906
TI  - Scope of the reductive aldol reaction: application to aromatic carbocycles and
      heterocycles.
AB  - The reductive aldol reaction of electron deficient aromatic compounds has been
      investigated and found to be a viable method for carbon-carbon bond formation.
      Reductions under ammonia and ammonia-free conditions were both capable of
      facilitating the aldol reaction although the latter showed more scope for
      reaction with enolisable aldehydes. Moreover, reduction under ammonia-free
      conditions allowed the addition of Lewis acids which improved stereoselectivity
      to favour the anti stereoisomer. Production of the syn diastereoisomer was
      possible through either one of two different protocols performed after partial
      reduction was complete. While the main emphasis of this paper concerns the
      reductive aldol reaction of electron deficient pyrroles, it was also shown that
      both benzenoid and furan aromatic compounds were amenable to such reducing
      conditions.

PMID- 14649907
TI  - Ene cyclisations of alpha-(prenyl)dialkylsilyloxy aldehydes: formation and
      oxidative cleavage of oxasilacyclohexanols.
AB  - A variety of routes are described for the synthesis of a-silyloxy aldehydes in
      which the silicon atom bears a prenyl side chain. These compounds are shown to
      undergo stereoselective carbonyl ene cyclisation under mildly Lewis acidic
      conditions and the derived silacycles are cleaved to afford single diastereomers
      of functionalised triols.

PMID- 14649908
TI  - Nitrenium ions. Reactions of N,N-dimethyl-p-benzoyloxyanilineiminium chloride
      with indoles and indolizines. X-ray structure of unexpected [2-chloro-4-(4
      dimethylaminophenyl-ONN-azoxy)phenylldimethylamine (azoxy derivative).
AB  - N,N-Dimethyl-p-nitrosoaniline reacts with benzoyl chloride affording a complex
      salt containing a cation, a hybrid between a nitrenium ion and an iminium ion.
      The salt reacts with nucleophiles (indoles, indolizines) yielding compounds
      characterized by a new carbon-nitrogen bond, derived from the nitrenium ion form.
      According to the type of nucleophile, the reaction, to differing extents, is in
      competition with an electron transfer process which leads to the formation of the
      dimer of the nucleophile and of the azoxy corresponding to the N,N-dimethyl-p
      nitrosoaniline. In one of the reactions studied, a chlorinated azoxy derivative
      was also isolated, and its structure was elucidated by X-ray analysis.

PMID- 14649909
TI  - Stereoselective synthesis of C-glycosides from carboxylic acids: the tandem Tebbe
      Claisen approach.
AB  - A variety of beta- or alpha-C-glycosides may be readily accessed in an entirely
      stereoselective fashion from esters derived from the reaction of carboxylic acids
      and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe
      methylenation and Claisen rearrangement. Though of wide scope, for example
      allowing the synthesis of 1-6 linked C-disaccharides, the methodology does not
      currently allow the synthesis of C-glycosyl alpha-amino acids.

PMID- 14649910
TI  - Development of two processes for the synthesis of bridged azabicyclic systems:
      intermolecular radical addition-homoallylic rearrangements leading to 2
      azanorborn-5-enes and neophyl-type radical rearrangements to 2
      azabenzonorbornanes.
AB  - Radical thiol additions to 7-azanorbornadienes give 7-thio-substituted 2
      azanorbornenes and Barton deoxygenations of 7-azabenzonorbornanols give 2
      azabenzonorbornanes. The processes both involve novel nitrogen-directed radical
      rearrangements. The kinetics and mechanisms of the reactions are also discussed.

PMID- 14649911
TI  - Control of diastereoselectivity in the crotylation and cinnamylation of aldehydes
      by the selection of ligands on allylic indium reagents.
AB  - Diastereoselective couplings of salicylaldehyde, anisaldehyde and 2
      pyridylaldehyde with crotyl- and cinnamylindium reagents were studied. The
      syl/anti selectivity was found to depend largely on the ligands on the indium
      atom of the allylic indium reagents. A syn-selective cinnamylation of
      salicylaldehyde was realized by the combination of cinnamyl acetate and indium(I)
      iodide, whereas an anti-selective coupling with salicylaldehyde was achieved by
      the indium trichloride/aluminium-mediated cinnamylation.

PMID- 14649912
TI  - Synthesis of N-acyl-N,alpha,alpha-trialkyl and N-acyl-alpha,alpha-dialkyl
      glycines by selective cleavage of Ugi-Passerini adducts. Qualitative assessment
      of the effect of substituents on the path and yield of reaction.
AB  - Several symmetric N-acyl-N,alpha,alpha-trialkyl glycine amides were synthesised
      by the Ugi-Passerini four-component reaction and subjected to selective cleavage
      with trifluoroacetic acid. In almost all cases it was possible to obtain the
      corresponding N-acyl-N,alpha,alpha-trialkyl and N-acyl-alpha,alpha-dialkyl
      glycines in fair to good yields directly from the reaction adducts. With some of
      the bulkier compounds our results show that the selectivity of cleavage is
      concentration dependent with respect to the acid, which suggests kinetically
      controlled processes. The isolation of a stable oxazolone as the product of some
      of the reactions seems to confirm that amide cleavage involves in all cases
      formation of an oxazolone-type derivative.

PMID- 14649913
TI  - Reflections on spontaneous asymmetric synthesis by amplifying autocatalysis.
AB  - Spontaneous generation of chirality was observed in the course of studying the
      mechanism of asymmetric autocatalysis by NMR in ZnR2 alkylation of pyrimidin-5
      aldehydes. A systematic study was carried out in order to discover its origins.
      Even in clean fresh non-glass reaction vessels spontaneous ee was clearly
      observed, and was not dependent on any single reaction parameter. For comparison
      it was demonstrated that enantiomerically pure Zn alkoxide catalyst could control
      the configuration of the reaction product even when present at below micromolar
      concentrations. The high propensity of the Soai reaction system to produce an
      enantiomerically enriched product without initial bias is suggested to result
      from stochastic effects. These are especially important in autocatalysis because
      all the final products can be derived by breeding from a small number of initial
      events. The statistical excess of one enantiomer in that set is sufficient to
      generate a measurable ee in the product. The process is aided by the requirement
      for dimerisation before the product is an active catalyst. An enumeration that
      rationalises these observations is provided.

PMID- 14649914
TI  - Synthesis of unprotected and borane-protected cyclic phosphines using Ru- and Mo-
      based olefin metathesis catalysts.
AB  - Ru- and Mo-based catalysts can be used in ring closing metathesis (RCM) reactions
      to synthesise cyclic phosphines protected as their borane complexes. The
      compatibility of the Schrock Mo-catalyst and the N-heterocyclic carbene Ru
      catalysts with this class of substrates is particularly noteworthy as asymmetric
      RCM (ARCM) is now emerging as a new tool for the preparation of homochiral
      phosphines. One of the key results is that the Mo-catalyst allows the ring
      closure of the unprotected diallylphenylphosphine with 95% conversion.

PMID- 14649915
TI  - Precise structure activity relationships in asymmetric catalysis using
      carbohydrate scaffolds to allow ready fine tuning: dialkylzinc-aldehyde
      additions.
AB  - The ready construction of 24 stereochemically and functionally diverse
      carbohydrate ligand structures from a core D-glucosamine scaffold has allowed the
      evaluation of broad ranging structure activity relationships in ligand
      accelerated zincate additions to aldehydes, with variations in deltadeltaG+/+(R
      S) of up to 5650 J mol(-1) that create opposing senses of asymmetric induction
      and that are consistent with models based on several ligand X-ray structures and
      molecular mechanics analysis. Factorial analysis of enantioselectivity using key
      dihedral angles and steric volume on N-2 also highlight the potential for the use
      of factorial design in ligand construction.

PMID- 14649916
TI  - Investigation of the configuration of alkyl phenyl ketone phenylhydrazones from
      ab initio 1H NMR chemical shifts.
AB  - Using ab initio GIAO calculations the experimental 1H NMR spectra of the E and Z
      isomers of alkyl phenyl ketone phenylhydrazones R1-C(Ph) = N-NH-Ph (R1 = Me, Et,
      iPr, and tBu) have been re-interpreted and deviations from Karabatsos' rule or
      from the assignment of Bellamy and Hunter have been discussed in the light of the
      optimized geometrical structures.

PMID- 14649917
TI  - Formation of gold-like metal-lustrous inclusion crystals from 1-phenyl-2,5-bis[5
      (tricyanoethenyl)-2-thienyl]pyrrole host and an electron-donating aromatic guest.
AB  - A novel pi-conjugated organic compound, 1-phenyl-2,5-bis[5-(tricyanoethenyl)-2
      thienyl]pyrrole, which bears two powerful electron-withdrawing tricyanoethenyl
      substitutents, readily yielded gold-like metal-lustrous inclusion crystals with a
      series of aromatic guest molecules such as toluene, p-xylene, anisole,
      dimethoxybenzenes and indene. All the inclusion compounds have a common
      stoichiometric ratio (host/guest) of 2 : 1. X-Ray structural analyses demonstrate
      that the structural feature for toluene included crystal is similar to those
      containing p-xylene, anisole, dimethoxybenzenes and indene.

PMID- 14649918
TI  - Hindered fluorescence quenching in an insulated molecular wire.
AB  - A [3]rotaxane 2 within 1(2) consisting of an anionic phenylene ethynylene
      dumbbell 2(4-) threaded through two cationic cyclophanes 1(2+) has been prepared
      using aqueous Glaser coupling. Stern-Volmer analysis of the fluorescence
      quenching using three different electron-acceptors (methyl viologen 13(2+),
      dipropyl-4,4'-bipyridinium disulfonate 14 and anthraquinone-2,6-disulfonate 15(2
      )) shows that the threaded cyclophanes inhibit electron-transfer from the excited
      state of the dumbbell by steric shielding, and by electrostatic shielding in the
      case of methyl viologen.

PMID- 14649919
TI  - Oligocyclization of 2-(hydroxymethyl)pyrroles with electron-withdrawing groups at
      beta-positions: formation and structural elucidation of porphyrinogens and
      hexaphyrinogens.
AB  - Acid-catalyzed oligomerization of 2-(hydroxymethyl)pyrroles bearing C6F5, 2,6
      Cl2C6H3, CF3 and CO2Et groups at beta-positions was examined. The reaction of
      ethyl pyrrole-3-carboxylates gave a mixture of oligomers and type I isomers of
      porphyrinogens and hexaphyrinogens were isolated when the other beta-substituents
      were sufficiently bulky, for example, mesityl, 2,6-Cl2C6H3 and C6F5 groups. On
      the other hand, the pyrroles having other electron-withdrawing groups afforded
      porphyrinogens as the only isolable products.

PMID- 14649920
TI  - Practice guideline for the assessment and treatment of patients with suicidal
      behaviors.

PMID- 14649921
TI  - Waveguide lenses with multimode interference for low-loss slab propagation.
AB  - It is shown that a nearly ideal two-dimensional focusing Gaussian beam can be
      synthesized by use of a linear combination of the two lowest-order even modes of
      an optical waveguide. This property can be used to couple laterally guided modes
      across slab waveguide regions with low loss. The technique is illustrated by use
      of a conventional multimode interference (MMI) geometry, in which the MMI coupler
      transforms the fundamental mode of an initial waveguide into a focusing Gaussian
      beam, which is then fed to a slab region. Two-dimensional beam propagation
      simulations show that the beam does not initially diverge in the slab region, but
      rather comes to a focus. A second MMI coupler then transforms the diverging beam
      back to the initial mode. A structure is designed that can couple the fundamental
      mode of a 9-microm-wide waveguide across an 88-microm-long slab region with only
      a 0.036-dB loss. This technique can be applied to improve the performance of
      small-angle waveguide crossings and integrated turning mirrors.

PMID- 14649922
TI  - High-quality-factor Bragg onion resonators with omnidirectional reflector
      cladding.
AB  - We propose to approximate a spherically symmetric Bragg resonator in an onionlike
      geometry. We develop a transfer-matrix theory for calculation of the quality
      factors and analyze the effect of the onion stem on cavity Q factors. We find
      that it is possible to achieve significant inhibition of spontaneous emission in
      an onion resonator with omnidirectional cladding layers.

PMID- 14649923
TI  - Apertureless scanning near-field optical microscopy: the need for probe-vibration
      modeling.
AB  - In apertureless scanning near-field optical microscopy (ASNOM), the probe
      vibration is often used to increase the detected signal. The useful signal is
      detected at the probe-vibration frequency by a lock-in amplifier. By comparing
      two-dimensional numerical results with an experimental scan, we show numerically
      that, to explain or predict the detected signal, a realistic model of ASNOM
      should take into account the scan of the probe as well as the probe vibration and
      the material properties.

PMID- 14649924
TI  - Polychromatic polarization singularities.
AB  - Elliptical polarization can appear in only monochromatic optical fields. In
      polychromatic vector fields the polarization is a Lissajous figure, but in only
      commensurate fields do the figures have well-defined shapes; in other fields the
      shapes are undefined. Nonetheless, I show that a given paraxial polychromatic
      vector field has a coherency ellipse field associated with it that contains
      polarization singularities and stationary points that are surrogates for the
      corresponding critical points of the parent optical field.

PMID- 14649925
TI  - Polarimetric and spectral changes in random electromagnetic fields.
AB  - Beginning with a recently formulated unified theory of coherence and polarization
      for random electromagnetic fields, we show how partially polarized light can be
      generated through correlation of unpolarized components. The effect is
      demonstrated by use of a Mach-Zehnder interferometer, showing the possibility of
      producing light with adjustable spectral density and an adjustable degree of
      polarization.

PMID- 14649926
TI  - Deterministic phase unwrapping in the presence of noise.
AB  - We present a new Fourier-based exact solution for deterministic phase unwrapping
      from experimental maps of wrapped phase in the presence of noise and phase
      vortices. This single-step approach has superior performance for images with high
      phase gradients or insufficient digital sampling approaching 2pi/pixel and
      therefore performs as a fast and practical solution for the phase-unwrapping
      problem for experimental applications in applied optics, physics, and medicine.

PMID- 14649927
TI  - Extreme outages caused by polarization mode dispersion.
AB  - We study the dependence on fiber birefringence of the bit-error rate (BER) caused
      by amplifier noise in a linear optical fiber telecommunication system. We show
      that the probability-distribution function of the BER obtained by averaging over
      many realizations of birefringent disorder has an extended tail that corresponds
      to anomalously large values of BER. We specifically discuss the dependence of the
      tail on such details of pulse detection at the fiber output as setting the clock
      and filtering procedures.

PMID- 14649928
TI  - Instantaneous quadrature low-coherence interferometry with 3 x 3 fiber-optic
      couplers.
AB  - We describe fiber-based quadrature low-coherence interferometers that exploit the
      inherent phase shifts of 3 x 3 and higher-order fiber-optic couplers. We present
      a framework based on conservation of energy to account for the interferometric
      shifts in 3 x 3 interferometers, and we demonstrate that the resulting
      interferometers provide the entire complex interferometric signal instantaneously
      in homodyne and heterodyne systems. In heterodyne detection we demonstrate the
      capability for extraction of the magnitude and sign of Doppler shifts from the
      complex data. In homodyne detection we show the detection of subwavelength sample
      motion. N x N (N > 2) low-coherence interferometer topologies will be useful in
      Doppler optical coherence tomography (OCT), optical coherence microscopy, Fourier
      domain OCT, optical frequency domain reflectometry, and phase-referenced
      interferometry.

PMID- 14649929
TI  - Non-Gaussian statistics of soliton timing jitter induced by amplifier noise.
AB  - Based on first-order perturbation theory of the soliton, the Gordon-Haus timing
      jitter induced by amplifier noise is found to be non-Gaussian distributed. Both
      frequency and timing jitter have larger tail probabilities than Gaussian
      distribution given by the linearized perturbation theory. The timing jitter has a
      larger discrepancy from Gaussian distribution than does the frequency jitter.

PMID- 14649930
TI  - Comparison of closed-loop and open-loop feedback schemes of message decoding
      using chaotic laser diodes.
AB  - An experimental study of a chaotic optical communication scheme using an external
      cavity laser diode to encode a message is reported. The message is decoded in
      closed- and open-loop receiver schemes. Both schemes show effective decoding of a
      1-GHz message. The synchronization and effectiveness of encoding are compared in
      both schemes.

PMID- 14649931
TI  - Inscription of fiber Bragg gratings by ultraviolet femtosecond radiation.
AB  - We report on what is to our knowledge the first fabrication of fiber Bragg
      gratings by UV femtosecond radiation. The Bragg gratings, with photoinduced
      refractive-index modulation up to 1.92 x 10(-3) in H2-loaded SMF-28 and up to
      1.05 x 10(-3) in Nufern GF1 fibers, were written by high-intensity (31-77-GW/cm2)
      femtosecond pulses at 264 nm. The dependence of the refractive-index modulation
      on intensity at equal fluences points to a two-photon absorption mechanism for
      grating inscription.

PMID- 14649932
TI  - Circular Dammann grating.
AB  - A circular Dammann grating that can produce circular equal intensities at various
      orders in the far field is described. A set of parameters such as order, circular
      number, uniformity, and diffraction efficiency has been defined to describe the
      novel diffractive phase elements. Numerical solutions of binary-phase (0, pi)
      circular Dammann gratings are given. The results of experiments with a four-order
      circular Dammann grating made by a lithographic technique are presented. This
      novel diffractive optical element should be highly interesting in a wide variety
      of practical applications.

PMID- 14649933
TI  - Fractional Hankel transform studied by charge-amplitude state representations and
      complex fractional Fourier transformation.
AB  - Starting from a complex fractional Fourier transformation [Opt. Lett. 28, 680
      (2003)], it is shown that the integral kernel of a fractional Hankel
      transformation is equivalent to the matrix element of an appropriate operator in
      the charge-amplitude state representations; i.e., the fractional Hankel
      transformation is endowed with a definite physical meaning (definite quantum
      mechanical representation transform).

PMID- 14649934
TI  - Focusing of light by zone plates in Selfoc gradient-index lenses.
AB  - We study the diffraction fields in a hybrid diffractive-gradient-index element
      composed of an amplitude zone plate and a quarter-pitch Selfoc gradient-index
      lens under uniform illumination. Focal positions of the diffractive orders and
      zone-plate diffraction efficiencies are measured, thereby validating the existing
      theoretical results.

PMID- 14649935
TI  - Generation of nondiffracting Bessel beams by use of a spatial light modulator.
AB  - A laser beam with phase singularities is an interesting object to study in optics
      and may have important applications in guiding atoms and molecules. We explore
      the characteristics of a singularity in a nondiffracting Bessel beam
      experimentally by use of a programmable spatial light modulator with 64-level
      phase holograms. The diffraction efficiency with 64-level phase holograms is
      greatly improved in comparison with that obtained with a binary grating. The
      experiments show that the size and deflection angle of the beam can be controlled
      in real time. The observations are in agreement with scalar diffraction theory.

PMID- 14649936
TI  - Offset compensation by use of amplitude-modulated sidebands in optical frequency
      standards.
AB  - We present a general method for continuously measuring and compensating for
      offsets (due to residual amplitude modulation, parasitic resonances, or
      electronic offset voltages, for example) in frequency stabilization systems. The
      spectral power distribution of the oscillator waveform is modified by amplitude
      modulated sidebands, and the error signal is corrected to null the induced
      periodic lock-point shifts. We demonstrate significant improvements to the
      frequency stability of standards based on cryogenic optical resonators and
      molecular iodine.

PMID- 14649937
TI  - Asymmetric multiple-quantum-well laser diodes with wide and flat gain.
AB  - Asymmetric multiple-quantum-well laser diodes with wide and flat gain spectra
      were designed, fabricated, and analyzed. The active layer was composed of three
      10-nm, one 8-nm, and two 6-nm 0.5% compressive strained wells and four 10-nm and
      one 5-nm 0.4% tensile strained barrier layer. Measured spectra of antireflection
      coated ridge waveguide laser diodes with such quantum-well structures have shown
      that -1-dB spectral gain bandwidth can be as large as 90 nm.

PMID- 14649938
TI  - Power scaling method for 2-microm diode-cladding-pumped Tm(3+)-doped silica fiber
      lasers that uses Yb(3+) codoping.
AB  - Unidirectional dual-wavelength pumping at 805 and 975 nm of a Tm(3+)-doped silica
      double-clad fiber laser that has been codoped with Yb(3+) is demonstrated. With
      equal 2-wt. % concentrations of the Tm(3+) and Yb(3+) ions, slope efficiencies of
      49% (57%) and 35% (40%) with respect to the launched (absorbed) pump power of the
      805- and 975-nm pump wavelengths, respectively, were obtained. Efficient Yb(3+) -
      > Tm(3+) energy transfer and efficient cross relaxation combined with minimal
      upconversion losses were thus operating. At the maximum output power of 18 W, the
      fiber laser operated at a center wavelength of 2050 nm.

PMID- 14649939
TI  - Directly diode-pumped Yb3+:SrY4(SiO4)3O regenerative amplifier.
AB  - We report a regenerative amplifier based on an Yb-doped apatite crystal:
      Yb3+:SrY4(SiO4)3O (Yb:SYS). We obtained 420-fs pulses at a central wavelength of
      1066 nm with an energy of 100 microJ at 300 Hz after compression. To the best of
      our knowledge, this system is the first regenerative amplifier based on an Yb:SYS
      crystal and provides duration among the shortest ones generated by a directly
      diode-pumped regenerative amplifier.

PMID- 14649940
TI  - Phase stabilization of an octave-spanning Ti:sapphire laser.
AB  - We obtain direct stabilization of the carrier-envelope phase for a standard x
      folded geometry, octave-spanning, Ti:sapphire laser. The in-loop accumulated
      carrier-envelope phase error is 0.175 rad (1.65 mHz to 102 kHz). Intracavity
      continuum generation, which is responsible for the octave bandwidth, is
      characterized through measurement of the beam parameters.

PMID- 14649941
TI  - Phase-shifting algorithm to achieve high-speed long-depth-range probing by
      frequency-domain optical coherence tomography.
AB  - Standard Fourier-domain optical coherence tomography (FDOCT) suffers from the
      presence of autocorrelation terms that obscure the object information and degrade
      the sensitivity and signal-to-noise ratio. By exploiting the phase information of
      the recorded interferograms, it is possible to remove those autocorrelation terms
      and to double the measurement range. However, standard phase-retrieval algorithms
      need three to five interferograms. We present a novel technique that shows all
      the features of complex FDOCT with only two recorded interferograms.

PMID- 14649942
TI  - Effect of surface roughness on determination of bulk tissue optical parameters.
AB  - Monte Carlo simulations have been conducted to investigate the effect of surface
      roughness on the inverse determination of bulk optical parameters. Results show
      that mus, mua, and g can be overestimated by an order of magnitude for thin slab
      tissue samples with a moderate index mismatch at the interfaces if typical
      surface roughness is neglected. Measurements of Intralipid samples between glass
      windows with smooth and rough surfaces have been carried out and agreement was
      found between the numerical and the experimental data. This study suggests that
      the surface roughness should be taken into account for both in vitro and in vivo
      determination of bulk tissue optical parameters.

PMID- 14649943
TI  - Macromolecular structure of cellulose studied by second-harmonic generation
      imaging microscopy.
AB  - The macromolecular structure of purified cellulose samples is studied by second
      harmonic generation (SHG) imaging microscopy. We show that the SHG contrast in
      both Valonia and Acetobacter cellulose strongly resembles that of collagen from
      animal tissues, both in terms of morphology and polarization anisotropy.
      Polarization analysis shows that microfibrils in each lamella are highly aligned
      and ordered and change directions by 90 degrees in adjacent lamellae. The angular
      dependence of the SHG intensity fits well to a cos2 theta distribution, which is
      characteristic of the electric dipole interaction. Enzymatic degradation of
      Valonia fibers by cellulase is followed in real time by SHG imaging and results
      in exponential decay kinetics, showing that SHG imaging microscopy is ideal for
      monitoring dynamics in biological systems.

PMID- 14649944
TI  - Distributed measurement of chromatic dispersion by four-wave mixing and Brillouin
      optical-time-domain analysis.
AB  - A new nondestructive method for measuring the spatial distribution of chromatic
      dispersion along an optical fiber is presented. It is based on using Brillouin
      optical time-domain analysis to probe the power distribution of the four-wave
      mixing generated by two continuous-wave lasers. The results obtained prove that
      this new method is capable of providing better performance than comparable
      techniques. Furthermore, sensing the variations of Brillouin gain maximum
      produces additional information about the fiber, such as presence of strain and
      concentration of GeO2.

PMID- 14649945
TI  - Fast optical switching via stimulated Raman adiabatic passage.
AB  - We demonstrate a new approach to fast optical switching with a technique based on
      stimulated Raman adiabatic passage in which a laser pulse switches the probe
      field on and off via another coupling pulse. This new kind of optical switching
      is not limited by the decay rate of an excited state and can operate in the
      subnanosecond time domain. The experimental observation in Rb atomic vapor is in
      good agreement with numerical simulations.

PMID- 14649946
TI  - Dissipative soliton in an amplifier with a Bragg grating.
AB  - A dissipative soliton in an amplifier with a Bragg grating is numerically
      investigated by direct simulation of Maxwell-Bloch equations. The result of the
      simulation indicates that a solitary wave can exist in such a medium. However,
      the pulse shape of the dissipative soliton is asymmetrical because of the gain
      saturation effect. This gain saturation effect results from the high power of the
      ultrashort dissipative soliton. The influence of amplifier gain on the solitary
      wave is also investigated.

PMID- 14649947
TI  - 20 W of continuous-wave sodium D2 resonance radiation from sum-frequency
      generation with injection-locked lasers.
AB  - A 20-W all-solid-state continuous-wave single-frequency source tuned to the
      sodium D2a line at 589.159 nm has been developed for adaptive optical systems.
      This source is based on sum-frequency mixing two injection-locked Nd:YAG lasers
      in lithium triborate in a doubly resonant external cavity. Injection locking the
      Nd:YAG lasers not only ensures single-frequency operation but also allows the use
      of a single rf local oscillator for Pound-Drever-Hall locking both the injection
      slave and the sum-frequency cavities. We observe power-conversion efficiencies in
      excess of 55% and a linearly polarized diffraction-limited output tunable across
      the sodium D2 line (589.156 to 589.160 nm) with no change in output power and
      with high amplitude and pointing stability.

PMID- 14649948
TI  - Microsecond pulsed optical parametric oscillator pumped by a Q-switched fiber
      laser.
AB  - We report on what is to our knowledge the first optical parametric oscillator
      (OPO) pumped by microsecond pulses from a wavelength-tunable solid-state laser.
      The singly resonant OPO (SRO) is based on a periodically poled LiNbO3 crystal and
      pumped with 2.1-micros-long pulses from an actively Q-switched Yb fiber laser. At
      an average fiber laser power of 3.6 W, the SRO generates 1.9-micros-long pulses
      with a repetition rate of 25 kHz and an average power of 560 mW at 3360 nm. The
      SRO was tuned from 1518 to 1634 nm (signal) and from 3145 to 3689 nm (idler) via
      the crystal temperature and poling period. By all-electronic tuning of the fiber
      laser wavelength over 19 nm, tuning of the mid-infrared idler wavelength over 195
      nm was achieved.

PMID- 14649949
TI  - Scalar modulation instability in the normal dispersion regime by use of a
      photonic crystal fiber.
AB  - Modulation instability at high frequencies has been demonstrated in the normal
      dispersion regime by use of a photonic crystal fiber. This fiber-optic parametric
      generator provides efficient conversion of red pump light into blue and near
      infrared light.

PMID- 14649950
TI  - Evolution of localization in frequency for modulated light pulses in a
      recirculating fiber loop.
AB  - We present an experimental demonstration of the evolution of localization in
      frequency of light pulses that are repeatedly kicked by phase modulation and then
      propagated along equally spaced lengths of fiber with weak dispersion. The
      experiment was performed with a long fiber recirculating loop that allows us to
      follow the pulse's spectral changes after each cycle.

PMID- 14649951
TI  - Optical multisoliton generation in nematic liquid crystals.
AB  - The nonlocal nonlinearity stemming from molecular reorientation in nematic liquid
      crystals supports the formation of multiple solitary waves, following the onset
      of spatial modulational instability from both wide and focused input beams. We
      report experimental observations of such phenomena at power levels of hundreds of
      milliwatts in planar cells with a voltage bias.

PMID- 14649952
TI  - Noise in superresolution reconstruction.
AB  - Recently there has been a significant interest in reconstructing a high
      resolution (HR) image based on a set of low-resolution (LR) images with relative
      displacement. These images are typically undersampled with respect to the image
      spectrum of a HR image. I show that, although ideally a resolution increase of N
      times is possible with N LR images, in a practical system noise is a limiting
      factor that increases substantially as we approach this theoretical
      superresolution limit. For one dimension and a special case with two LR images, I
      present an analytical result of the noise amplification as a function of their
      displacement. This is defined as a condition number of the superresolution
      system, with the associated definitions of a well-conditioned and ill-conditioned
      superresolution reconstruction system.

PMID- 14649953
TI  - Holographic solitons in photorefractive dissipative systems.
AB  - A new kind of holographic soliton is proposed for a photorefractive dissipative
      system consisting of a biased photorefractive crystal and a strong pump beam with
      a uniform spatial distribution in both transverse dimensions. The self-trapping
      beam in the system can evolve into a spatial soliton when it couples coherently
      with the pump beam by two-wave mixing. Unlike the holographic solitons recently
      proposed by Cohen et al. [Opt. Lett. 27, 2031 (2002)], the most unique features
      of the present solitons are that they have a fixed amplitude and width that are
      determined completely by the system parameters and that their existence
      conditions are independent of the polarity of the bias field. Numerical
      simulations show that these solitons are stable relative to small perturbations.

PMID- 14649954
TI  - Polarization holographic gratings in hybrid solgel films doped with Disperse Red
      1.
AB  - Polarization holographic gratings in sp configuration are written at 488 nm in
      photorefractive organic-inorganic films based on SiO2. The films, prepared by a
      solgel technique, contain Disperse Red 1, carbazole units, and 2,4,7-trinitro-9
      fluorenone. The gratings are characterized by their diffraction efficiency for a
      632.8-nm probe. The polarization gratings act as a half-wave plate, and the
      diffraction efficiency is independent of the polarization direction of the probe.

PMID- 14649955
TI  - Phase-shifting lateral shearing interferometer with two pairs of wedge plates.
AB  - We present a compact and robust phase-shifting lateral shearing interferometer
      that produces shearing fringes in orthogonal directions without any mechanical
      rotation or precise alignment. It consists of two pairs of wedge plates, a beam
      splitter, and a single CCD camera. Both phase-shifting and tilt for lateral
      shearing are achieved with two pairs of wedge plates, which can reduce systematic
      errors caused by external vibration and atmospheric disturbance.

PMID- 14649956
TI  - Compact and fault-tolerant photonic crystal add-drop filter.
AB  - We propose an add-drop filter consisting of two adjacent waveguides carved into a
      two-dimensional photonic crystal that is etched through a standard guiding
      structure. This filter is based on distributed energy transfer via the frequency
      selective intermediate conversion of the fundamental guided mode to a high-order
      low-group-velocity mode. This geometry circumvents the fabrication sensitivity on
      the single-hole scale of previous cavity-based designs. Combining distributed
      energy transfer and reduced group velocity preserves compactness. The design is
      analytically optimized with a coupled-mode approach.

PMID- 14649957
TI  - Mo:Y multilayer mirror technology utilized to image the near-field output of a Ni
      like Sn laser at 11.9 nm.
AB  - Although bright x-ray sources exist at shorter wavelengths, the development of
      sophisticated diagnostics with x-ray laser sources has been restricted to
      wavelengths longer than 12.5 nm because of the limitations of the widely used
      Mo:Si multilayer mirrors. With the novel Mo:Y multilayer mirrors that we present,
      many x-ray laser applications can be extended to the 7-12-nm range. We
      demonstrate this new capability by imaging the near-field output of the Ni-like
      Sn laser at 11.9 nm.

PMID- 14649958
TI  - 4 x 4 optical cross-point packet switch matrix with minimized path-dependent
      optical gain.
AB  - Packet-switching characteristics are optimized across an integrated 4 x 4 optical
      cross-point switch matrix based on active vertical coupler switch cells. Optical
      gain is demonstrated across the entire matrix with a <3-dB difference between the
      shortest and longest switching paths.

PMID- 14649959
TI  - Resonant scattering of surface-plasmon polariton pulses by nanoscale metal
      defects.
AB  - We have theoretically investigated the dynamics of the scattering of surface
      plasmon polariton (SPP) pulses by single nanoscale metal defects through a
      rigorous calculation of the time dependence of the reflected and transmitted SPP
      and of the angular distribution of the scattered light. SPP resonances that occur
      at deep Gaussian grooves are probed with SPP pulses, the resonant scattering
      being unequivocally manifested by (a) the exponential tails of the scattered SPP
      and light pulses and (b) the delay time of the transmitted SPP pulse.

PMID- 14649960
TI  - Optical pulse compression to 3.4 fs in the monocycle region by feedback phase
      compensation.
AB  - We compensated for chirp of optical pulses with an over-one-octave bandwidth (495
      1090 nm; center wavelength of 655.4 nm) produced by self-phase modulation in a
      single argon-filled hollow fiber and generated 3.4-fs, 1.56 optical-cycle pulses
      (500 nJ, 1-kHz repetition rate). This was achieved with a feedback system
      combined with only one 4-f phase compensator with a spatial light modulator and a
      significantly improved phase characterizer based on modified spectral phase
      interferometry for direct electric-field reconstruction. To the best of our
      knowledge, this is the shortest pulse in the visible-to-infrared region.

PMID- 14649961
TI  - Longitudinal coherence measurements of a transient collisional x-ray laser.
AB  - We present what is to our knowledge the first longitudinal coherence measurement
      of a transient inversion collisional x-ray laser. We investigated the picosecond
      output of a Ni-like Pd x-ray laser at 14.68 nm generated by the COMET laser
      facility at the Lawrence Livermore National Laboratory. Interference fringes were
      generated with a Michelson interferometer setup in which a thin multilayer
      membrane was used as a beam splitter. We determined the longitudinal coherence
      for the 4d1S0 --> 4p1P1 lasing transition to be approximately 400 microm (1/e
      half-width) by changing the length of one interferometer arm and measuring the
      resultant variation in fringe visibility. The inferred gain-narrowed linewidth of
      approximately 0.29 pm is a factor of 4 less than previously measured in quasi
      steady-state x-ray laser schemes.

PMID- 14649962
TI  - Implementation of electro-optic spectral shearing interferometry for ultrashort
      pulse characterization.
AB  - Electro-optic spectral shearing interferometry is implemented for the highly
      sensitive characterization of ultrashort pulses from a free-running source. A
      simple phase-locked-loop clock recovery circuit is used to extract the high
      frequency microwave clock signal to drive the phase modulator for spectral
      shearing. We demonstrate accurate full temporal characterization of 200-fs pulses
      from an optical parametric oscillator at 5-pW average power.

PMID- 14649963
TI  - Surveillance of commensal rat and shrew populations in the Bangkok area with
      references to flea index as the risk indicator of plague.
AB  - Commensal rats and shrews were trapped from 47 fresh food markets in Bangkok
      during the two study periods in the same markets: 21st June to 28th December 1999
      and 1st March to 31st May 2000. Trapping was performed using wire live traps on
      three consecutive nights in each period. The trapped animals were identified for
      taxonomic species and flea infestation. Fleas were collected, identified and
      counted. Four species of rodents: Rattus norvegicus, Rattus rattus, Rattus
      exulans and Mus musculus, and one species of shrew: Suncus murinus were trapped
      in comparable numbers during the two study periods. Among the 1177 animals
      trapped, 84.3 per cent were R. norvegicus. Regarding sex prevalence, a higher
      number of female animals were trapped compared to males. Almost all the fleas
      collected were Xenopsylla cheopis, and there were very few Ctenocephalidesfelis
      felis. Flea index based on the number of X. cheopis was 0.65 for all over
      Bangkok. Based on the geographical area of Bangkok, the inner area had the
      highest rodent population and the highest flea index of 0.86. Therefore, the
      inner region should be the priority for sanitation improvement.

PMID- 14649964
TI  - Comparative health survey of Luangpraot-Tanlium and Marialai communities Lat
      Krabang district, Bangkok.
AB  - The objective of the present descriptive study was to investigate the demographic
      and health status of Thai people in Luangpraot-Tanlium (LPT) and Marialai
      community (MRL) of Lat Krabang district in Bangkok. These two communities are the
      pilot project of the "Healthy Community" of Lat Krabang BMA hospital. The total
      number of households of LPT and MRL are 263 and 240, the population is 957 and
      1057, males to female ratio was 1:1.2. The median household income of the
      residents in both communities is 9,000 baht/month/family. About 49 per cent of
      people have no health insurance and 22 per cent have social welfare (for
      underserved population). Both communities are comparable in terms of sex, age,
      marital status, contraceptive use, history of physical examination, chronic
      diseases and environmental sanitation. MRL has more trade certificate educational
      attainment, history of Pap smears and voluntary health insurance than LPT. LPT
      seemed to be prominent to have more governmental employees and governmental
      subsidised reimbursement for health care access. People of LPT required health
      and dental care more often from hospital health teams than MRL. They needed
      annual health check ups, care for chronic diseases and mosquito eradication. LPT
      also reported more garbage disposal using the burning method, greater use of rain
      and tap water and significant poorer sewerage and toilet facility systems when
      compared with MRL. The reported prevalence of chronic diseases are 1.7 fold
      higher in MRL than in LPT. Percentage of vaccination coverage (BCG, OPV&DPTI-II
      III, HBVI-II-III, Measles vaccine) among children aged less than 1 year was 100
      per cent and 1-5 years was 90 per cent (OPV & DPTIV-V).

PMID- 14649965
TI  - The pattern of prostate-specific antigen responses following hormonal therapy in
      Thai men with bone metastatic prostate cancer.
AB  - OBJECTIVE: To study the pattern of prostate-specific antigen (PSA) responses and
      prognostic factors following hormonal therapy in Thai men with bone metastatic
      prostate cancer. MATERIAL AND METHOD: Forty-four patients with bone metastatic
      prostate cancer treated by bilateral orchiectomy were retrospectively studied for
      PSA responses during follow-up. The endpoint was time to PSA biochemical failure.
      PSA pattern and the prognostic factors were evaluated. RESULTS: PSA levels
      regressed to PSA nadir level in all patients. Time to 50 per cent PSA regression,
      time to PSA nadir level and time to biochemical failure were 2.1, 6.7 and 11.2
      months, respectively. While biochemical failure was present, all patients were
      alive and had stable clinical conditions. Tumor grading was an important
      prognostic factor while age and pretreatment PSA level were not a significant
      indicator. Times to biochemical failure in the patients with well, moderate and
      poor differentiated tumors were 19.3, 10.0 and 9.3 months, respectively.
      CONCLUSION: Following bilateral orchiectomy in Thai men with bone metastatic
      prostate cancer, PSA level decreased continuously to the PSA nadir level in 6-7
      months and stable for a period then it increased, known as biochemical failure.
      The patients with a well differentiated tumor had a significantly longer time to
      biochemical failure when compared to the patients with a moderate or poor
      differentiated tumor.

PMID- 14649966
TI  - Epstein-Barr virus-associated peripheral T-cell lymphoma with gastrointestinal
      tract involvement.
AB  - Peripheral T-cell lymphoma (PTCL) is a group of diseases which are common in Asia
      and areas of South and Central America. They are highly associated with the
      Epstein-Barr virus (EBV) infection. In the present study the authors evaluated
      patients with gastrointestinal involvement of PTCL with respect to clinical
      findings and outcome, pathologic features, and molecular analysis for EBV
      infection and the clonality of tumor cells. From January 1997 through December
      2000, 7 patients with gastrointestinal tract involvement of PTCL were identified.
      The frequency of gastrointestinal tract involvement in the various types of PTCL
      was 5.4 per cent (7 of 129 cases). The pertinent clinical features were prolonged
      fever, weight loss, anemia, hepatosplenomegaly, lymphadenopathy, multiorgan
      involvement, and gastrointestinal bleeding. Laboratory results showed a
      significantly high serum level of alkaline phosphatase and lactate dehydrogenase,
      and abnormal coagulograms. Five patients died within 4 months after onset of
      illness, while two were in complete remission after chemotherapy. The tumor cell
      morphology was classified into three categories: small-sized cells, mixed medium-
      and large-sized cells, and large-sized cells. The antigenic phenotypes of the
      tumor cells were LCA+, CD3+, CD15-, CD16-, CD30-, CD45R0+, CD57-, CD68-, EMA-,
      betaF1-, granzyme B+, TIA-1+, and p53+. The expression of CD4, CD8, CD56 and CD20
      was variable. EBV-RNA expression by in situ hybridization (EBER-ISH) study was
      positive and T-cell receptor (TCR) beta and/or gamma gene rearrangements were
      detected in all patients. DNA sequence analysis showed high identity to the human
      TCR germline gene. PTCL with gastrointestinal tract involvement was associated
      with EBV infection. The tumor cells were mature T cells with some NK-cell
      antigenic expression and all demonstrated TCR gene rearrangements.

PMID- 14649967
TI  - Success rate of vaginal birth after cesarean delivery at Maharaj Nakorn Chiang
      Mai Hospital.
AB  - OBJECTIVE: To study the success rate of vaginal birth after cesarean delivery
      (VBAC) in pregnant women with prior cesarean scar who delivered at Maharaj Nakorn
      Chiang Mai Hospital. STUDY DESIGN: Prospective descriptive study. SETTING:
      Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand. SUBJECT: One hundred
      and seventy-seven pregnant women with one or two prior cesarean deliveries, who
      attended the antenatal clinic and delivered at Maharaj Nakorn Chiang Mai Hospital
      between January, 2000 and September, 2002 were recruited with written informed
      consents. INTERVENTION: Systematic non-directive counseling concerning VBAC
      compared with elective repeated cesarean delivery was given to the pregnant
      women. Couples freely chose their preferred route of delivery and were informed
      that they could change their mind at anytime. Subjects attended the high risk
      antenatal care clinic. Patients who requested repeated cesarean deliveries were
      scheduled for the operation at 38 weeks of gestation. All VBAC patients were
      admitted to the labor unit when in labor and were closely monitored. Labor and
      postpartum information was prospectively recorded. MAIN OUTCOME MEASURE: Success
      rate of VBAC. RESULT: Of 177 counselled women, 118 chose VBAC, 54 chose repeated
      cesarean and 5 could not make a decision. Thirty-three of the 177 cases were
      excluded, leaving 98 in the VBAC group and 46 in the repeated cesarean group.
      Baseline characteristics of the patients in both groups were not significantly
      different. Nineteen of the 98 cases were delivered by cesarean section because of
      obstetric indications (12/19) and changed their minds during the antenatal period
      (7/19). Forty-three of 79 cases had successful vaginal delivery, and 36 underwent
      repeated cesarean deliveries due to obstetric indications (19/36) and changed
      their minds during labor (17/36). The success rate of VBAC after trial of labor
      was 54.4 per cent (43 in 79). No uterine rupture or serious complication occurred
      in the present study. CONCLUSION: The attitude for VBAC was 66.7 per cent and the
      success rate of VBAC after trial of labor was 54.4 per cent in the present
      series. Several cesarean deliveries could be avoided by the VBAC policy. Unlike
      other previous reports, the failure rate of VBAC was rather high. This was
      associated with many factors such as change of mind due to labor pain.

PMID- 14649968
TI  - Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch
      for estrogen replacement therapy.
AB  - OBJECTIVES: To evaluate the efficacy, safety and acceptability of a seven-day,
      transdermal estradiol patch, in the treatment of menopausal symptoms. DESIGN:
      Open-label trial. SETTING: Hat Yai Regional Hospital, Thailand. SUBJECTS:
      Hysterectomized women with surgical or natural menopause. METHOD: The clients
      received a 12.5 cm2 matrix patch, containing 3.9 mg of estradiol delivering 0.05
      mg/day, once a week for six months. The efficacy, safety, and acceptability were
      evaluated at the end of 1-, 3- and 6-months. RESULTS: Six-month responses were
      analyzed among 50 enrolled patients. The mean estradiol level/Follicle
      Stimulating Hormone/Lutienizing Hormone were 27.88/70.03/31.19,
      44.08/53.37/26.86, and 42.43/48.53/24.39 pg/ml, mIU/L, mIU/L at admission, 1- and
      3-months, respectively. The average climacteric score was 27.18, 16.60, 12.78,
      and 12.18 at admission, 1-, 3- and 6-month, respectively. At least 94 per cent of
      patches were not dislodged more than one quarter. The most common skin irritation
      was itching, followed by erythema, vesicle, and burning sensation. The patches
      were generally well tolerated, and acceptability was satisfactory. CONCLUSION:
      Transdermal estradiol patch effectively reduced the severity of menopausal
      symptoms, measured by modified climacteric score. Adhesion was found to be
      excellent. In actual clinical practice, the transdermal patch should be
      appropriately introduced to tolerant users.

PMID- 14649969
TI  - A randomized comparison of ginger and vitamin B6 in the treatment of nausea and
      vomiting of pregnancy.
AB  - OBJECTIVE: To compare the efficacy of ginger to vitamin B6 in the treatment of
      nausea and vomiting of pregnancy. STUDY DESIGN: A randomized double-blind
      controlled trial. SETTING: The Department of Obstetrics and Gynecology, Bangkok
      Metropolitan Administration Medical College and Vajira Hospital. SUBJECTS: Women
      with nausea and vomiting of pregnancy at or before 16 weeks of gestation, who
      attended the antenatal care clinic. The subjects requested anti-emetics, had no
      medical complications, non-hospitalized and were able to attend a one week follow
      up visit. From November, 1999 to November 2000, 138 women participated and gave
      consent for the study. METHOD: The subjects were randomly allocated into two
      groups to take either 500 mg of ginger orally or an identical 10 mg of vitamin B6
      one capsule three times daily for three days. Subjects graded the severity of
      their nausea using visual analogue scales before treatment and recorded the
      number of vomiting episodes in the previous 24 hours and again during three
      consecutive days of treatment. MAIN OUTCOME MEASURES: The change of nausea scores
      and the number of vomiting episodes during three days of treatment. RESULTS: The
      64 subjects in each group remained in the study. The demographic data were
      comparable in both groups. The ginger and vitamin B6 significantly reduced the
      nausea scores from 5.0 (SD, 1.99) to 3.6 (SD, 2.48) and 5.3 (SD, 2.08) to 3.3
      (SD, 2.07) respectively, with p < 0.001. The mean score change after treatment
      with ginger was 1.4 (2.21), less than with vitamin B6, which was 2.0 (2.19) but
      with no statistically significant difference (95% CI -1.4 to 0.2, p = 0.136). The
      ginger and vitamin B6 also significantly reduced the number of vomiting episodes
      from 1.9 (2.06) to 1.2 (1.75) and 1.7 (1.81) to 1.2 (1.50) respectively, with p <
      0.01. The mean number change after treatment with ginger was 0.7 (2.18), more
      than with vitamin B6, which was 0.5 (1.44) but with no statistically significant
      difference, (p = 0.498). There were some minor side effects in both groups such
      as sedation (26.6% vs 32.8%, p = 0.439), and heartburn (9.4% vs 6.3%, p = 0.510),
      a non-significant difference. CONCLUSION: The nausea score and the number of
      vomiting episodes were significantly reduced following ginger and vitamin B6
      therapy. Comparing the efficacy, there was no significant difference between
      ginger and vitamin B6 for the treatment of nausea and vomiting during pregnancy.

PMID- 14649970
TI  - Effect of chili pepper (Capsicum frutescens) ingestion on plasma glucose response
      and metabolic rate in Thai women.
AB  - OBJECTIVES: To evaluate the effect of 5 g fresh chili pepper (CAP) on glucose
      response after a glucose drink and metabolic rate (MR) in Thai women. MATERIAL
      AND METHOD: The glucose response after a glucose drink was evaluated in 10
      healthy women. The plasma glucose levels at 0, 15, 30 and 60 min after glucose
      load with and without 5 g fresh CAP were compared. Evaluation of MR was performed
      in an additional 12 subjects. MR was measured by the ventilated-hood indirect
      calorimetry system before and for 60 min after CAP ingestion. RESULTS: The rise
      of plasma glucose at 30 min after CAP ingestion was significantly lower than the
      rise of plasma glucose after a plain glucose drink by 20.6 per cent (p < 0.01).
      On the other hand, the CAP ingestion significantly increased MR above resting MR.
      Moreover, MR immediately increased by 20 per cent within a few minutes after CAP
      ingestion and showed a remarkable increase of 7.2-17.4 per cent from baseline for
      11 min. The significance of thermogenic change was present up to 30 min (p <
      0.05). CONCLUSIONS: Within 30 min after consumption of 5 g of Capsicum
      frutescens, plasma glucose level during the absorption period was significantly
      inhibited. The metabolic rate was also immediately increased after ingestion and
      sustained up to 30 min.

PMID- 14649972
TI  - A clinical study of crystal-proven gouty arthritis in a university hospital.
AB  - The clinical features of 567 patients with crystal proven gout (489 males, 78
      females) seen in a University Hospital in northern Thailand was reviewed. The
      mean age at onset and mean duration of disease was 60.0 +/- 11.7 years and 5.2 +
      4.8 years, respectively. Recurrent attacks accounted for 94 per cent. The knee
      and ankle were the 2 most common joints affected during the first attack and each
      one was seen in 55.6 per cent of cases. During a recurrent attack, the ankle,
      knee and first metatarsophalangeal joint were the 3 most common joints affected
      and were seen in 94.5 per cent, 81.2 per cent and 80.2 per cent of cases,
      respectively. Thirty-six per cent of the patients had tophi. Hypertension,
      hyperlipidemia, diabetes mellitus and ischemic heart disease were commonly
      associated diseases. Thirty-five per cent had renal calculi, and fifty-four per
      cent had renal insufficiency. Of 59 patients who tested with normal renal
      function, twelve per cent were hyperexcretor. The clinical features of gout seen
      in the university hospital in northern Thailand were similar to those reported in
      Bangkok, but with a higher incidence of tophaceous gout, renal failure and renal
      calculi.

PMID- 14649971
TI  - The efficacy of Thai capsaicin in management of overactive bladder and
      hypersensitive bladder.
AB  - This paper has been generated to provide information on the effectiveness of
      capsaicin treatment among patients with overactive or hypersensitive bladder. The
      evaluation process required approximately 14 (overactive bladder) and 11
      (hypersensitive bladder and primary detrusor instability) participants who
      received capsaicin intravesically. The solution consisted of capsaicin
      (concentration = 1 mM/L) diluted in 30 per cent ethanol solution 100 ml. All
      participants went through at least 1 urodynamic test 1 month before and after
      receiving capsaicin intravesical instillation. The capsaicin treatment for
      overactive and hypersensitive bladders was very effective. On the average,
      (overactive bladder) participants' voiding needs decreased from 16.5 +/- 4.8
      times/day to 8.6 +/- 2.5 times/day, leakage from 9.7 +/- 8.1 times/day to 2.4 +/-
      4.3 times/day, bladder capacity from 160.1 +/- 123.3 ml to 236.9 +/- 146.1 ml,
      and detrusor contraction from 71.1 +/- 29.2 cm/H2O to 57.3 +/- 27.2 cm/H2O. On
      average, (hypersensitive bladder and primary detrusor instability) participants'
      voiding needs decreased from (Day time) 19.45 +/- 17.99 times to 12.00 +/- 8.91
      times/day, (Night time) 7.09 +/- 6.03 times to 4.09 +/- 3.8 times, bladder
      capacity from 197.40 +/- 156.06 ml to 323.45 +/- 129.46 ml, and detrusor
      contraction from 32.64 +/- 22.77 cm/H2O to 36.64 +/- 19.22 cm/H2O. Capsaicin
      efficiency was rated very high for both overactive and hypersensitive bladder and
      primary detrusor instability. In Thailand, it has been possible to produce
      capsaicin using local chili supplies, thus the price of the drug itself is very
      economical. When considering the efficiency and the inexpensive cost of
      capsaicin, this treatment would be another great alternative for overactive and
      hypersensitive bladder cure.

PMID- 14649973
TI  - Effect of antifungal drugs on pathogenic Naegleria spp isolated from natural
      water sources.
AB  - Five of 16 strains of pathogenic Naegleria spp isolated from 350 natural water
      sources in Taling Chan District, Bangkok had similar molecular weights and
      zymogram patterns to those of Naegleria fowleri CDCVO 3081 and Thai strain. The
      in vitro effects of antifungal drugs (amphotericin B, ketoconazole, fluconazole
      and itraconazole) were tested at the following concentrations: amphotericin B
      0.01-0.55 microg/ml, ketoconazole 0.01-0.3 microg/ml, fluconazole 0.75-3.5 mg/ml
      and itraconazole 4-12 mg/ml respectively. Aliquots (15,000 cells/ml) of the
      amoebae were placed in the cells of the microtiter plate and incubated at 37
      degrees C. Amoebae from each treatment sample were exposed to one of the four
      antifungal drugs. Statistical analysis was done by dependent t-test. The
      sensitivity of the antifungal drugs (MIC50) was as follows: amphotericin B 0.03
      0.035 microg/ml ketoconazole 0.05-0.15 microg/ml fluconazole 1.75 mg/ml and
      itraconazole 8-9 mg/ml respectively (p < 0.005). CONCLUSION: Amphotericin B and
      ketoconazole are more active against Naegleria fowleri in vitro. The results of
      the present study should be used as an in vitro screening test for drugs that
      have potential amebicidal activity.

PMID- 14649974
TI  - Evaluation of the bedside glucose monitoring system in neonatal units.
AB  - OBJECTIVE: To evaluate the performance of a commercial reader compared with a
      laboratory method in neonates with a variety of diseases and conditions. PATIENTS
      AND METHOD: A total of 175 patients were included in the present study. Venous
      whole blood samples were analyzed with a commercial reader by trained nurse.
      Through the same sampling site, specimens were collected, spun and plasma were
      sent to the laboratory for measurement of plasma glucose. RESULTS: The regression
      analysis between the results of a commercial reader and laboratory glucose were
      significantly correlated (r = 0.97; p < 0.001) with the result as follows: A
      commercial reader = Laboratory glucose - 0.17 (n = 175). A positive slope of 0.04
      was found between hematocrit and difference between a commercial reader and
      laboratory plasma glucose. However, this correlation was of little clinical
      significance. CONCLUSIONS: A commercial reader showed a good correlation with the
      standard laboratory method for the measurement of plasma glucose in neonates with
      a variety of diseases and conditions.

PMID- 14649975
TI  - Equity in health : concept and data in Thailand.

PMID- 14649976
TI  - Family physicians--looking in the mirror.

PMID- 14649977
TI  - Delay in diagnosis: how do patients feel?

PMID- 14649978
TI  - Delay in diagnosis: how do patients feel?

PMID- 14649979
TI  - Family medicine. What's it all about?

PMID- 14649981
TI  - Dermacase. Churg-Strauss syndrome.

PMID- 14649980
TI  - Risk of varicella infection during late pregnancy.
AB  - QUESTION: I have a patient who contracted varicella at 26 weeks' gestation. She
      is very concerned and would consider termination if it were earlier in the
      pregnancy. What are the current predictions of risk for her fetus? ANSWER: Based
      on review of all available studies, we could not detect a single case of
      congenital varicella syndrome in the third trimester of pregnancy (0/208), as
      compared with 5/645 (0.78%) in the first and 9/592 (1.52%) in the second
      trimester (P < .01 third vs first and second). You can reassure your patient.

PMID- 14649982
TI  - Practice tips. Toenail splinting.

PMID- 14649983
TI  - Nutrition in your practice.

PMID- 14649984
TI  - Management of atrial fibrillation. Rhythm or rate? That is the question.

PMID- 14649985
TI  - Infertility evaluation and management. Strategies for family physicians.
AB  - OBJECTIVE: To review family physicians' role in investigation and management of
      infertile couples. QUALITY OF EVIDENCE: MEDLINE and PubMed were searched using
      the MeSH headings infertility, advanced maternal age, polycystic ovarian
      syndrome, clomiphene citrate, and insulin sensitizers. Bibliographies of review
      articles and textbooks were also searched. Review articles, randomized trials,
      observational studies, and case series are cited. MAIN MESSAGE: Approximately 8%
      of Canadian couples have difficulty conceiving. Mother's age significantly
      affects ability to conceive. Infertility assessment focuses on ovulatory
      dysfunction, tubal factors, sexual factors, and male factors. Women older than 35
      years more than 12 months infertile; women younger than 35 more than 18 months
      infertile; women likely to have such problems as anovulation, tubal disease, or
      endometriosis; women whose partners' semen tests abnormal; and women who request
      referral should be referred. Patients treated with clomiphene citrate should be
      aware of its potential side effects. CONCLUSION: Family physicians have an
      important role in preconception counseling. Detailed and focused assessment
      facilitates initial investigations and treatment and can identify couples who
      could benefit from referral for further assessment.

PMID- 14649986
TI  - Diagnosis and management of microscopic colitis.
AB  - OBJECTIVE: To describe microscopic colitis (MC) and a stepwise approach to its
      diagnosis and management. QUALITY OF EVIDENCE: MEDLINE was searched from January
      1996 to August 2002. Controlled trials were sought, but due to their relative
      rarity, most articles cited are well designed retrospective studies and reviews.
      MAIN MESSAGE: Microscopic colitis in both its collagenous and lymphocytic forms
      is a relatively common and important cause of diarrhea in middle-aged and elderly
      patients. It usually presents as chronic watery diarrhea. Results of endoscopic
      and radiologic examinations are normal; specific histologic findings are seen on
      colonic biopsy. Once the diagnosis is confirmed, we suggest a stepwise approach
      to therapy. First-line therapies include antidiarrheal agents; second-line
      include bismuth subsalicylates and budesonide; third-line include cholestyramine
      and 5-aminosalicylic acid agents. When patients fail to respond to these
      therapies, oral corticosteroids or immune modulatory therapy should be
      considered. For severe unresponsive cases, colectomy is the last resort.
      CONCLUSION: Microscopic colitis is an important cause of chronic diarrhea. Once
      the diagnosis is confirmed, a stepwise approach to treatment is suggested.

PMID- 14649987
TI  - Visiting family physicians and naturopathic practitioners. Comparing patient
      practitioner interactions.
AB  - OBJECTIVE: To explore similarities and differences in patient visits with family
      physicians (FPs) and naturopathic practitioners (NPs). DESIGN: Exploratory study
      combining quantitative and qualitative methods. SETTING: Southern Ontario.
      PARTICIPANTS: A purposeful sample of 10 practitioners (five FPs and five NPs
      matched for age, sex, and number of years in practice): each agreed to recruit
      three consecutive patients with new complaints to participate in the study. MAIN
      OUTCOME MEASURES: Patient and visit characteristics; qualitative (content
      analysis of audiotaped interactions) and quantitative (ie, patient-centred care
      scores) information was gathered and analyzed. RESULTS: Qualitative analysis
      revealed that information gathering and treatment planning were very similar
      whether patients were visiting FPs or NPs. Most important differences were length
      of interaction (mean 54 minutes for NPs and 16.5 minutes for FPs) and patients'
      reasons for visits. Naturopathic practitioners were more likely to recommend
      medications (usually natural health products) than FPs. Quantitative data
      suggested that patients perceived no differences in patient-centred care from FPs
      and NPs. CONCLUSION: Overall, there were more similarities than differences in
      visits to the two types of practitioners.

PMID- 14649988
TI  - Seniors' perceptions of their medical care. Before admission to a geriatric
      rehabilitation program.
AB  - OBJECTIVE: To review older patients' perceptions of their medical care before
      hospital admission and to determine whether there are common perceptions family
      physicians should address after discharge. DESIGN: Semistructured interviews with
      qualitative analysis. SETTING: Inpatient geriatric rehabilitation and assessment
      unit. PARTICIPANTS: Community-living seniors admitted from home or transferred
      from acute care hospitals. METHOD: Consecutively admitted patients were
      interviewed within a week of admission. Participants were asked open-ended and
      Likert-type questions. Responses were analyzed to uncover recurrent themes and
      descriptive statistics. MAIN FINDINGS: Patients thought physicians' personalities
      and ability to communicate were important factors in their satisfaction with care
      received. Loyalty to a physician was an important theme and might have made
      patients minimize their concerns about care. Most patients were confident in
      being discharged back into the care of their family physicians. CONCLUSION:
      Physicians' personalities and communication skills affected whether patients were
      satisfied with care. Older patients are loyal to their family physicians; they
      did not identify any issues for family physicians to address with them after
      discharge.

PMID- 14649989
TI  - Patients seeking care during acute illness. Why do they not see their regular
      physicians?
AB  - OBJECTIVE: To identify factors that predict whether patients prefer seeing their
      regular physicians and whether they do see their regular physicians during acute
      illness. DESIGN: Cross-sectional, population-based telephone survey. SETTING:
      Urban areas in southern Ontario. PARTICIPANTS: Random sample of 304 people who
      had regular physicians, insurance coverage, and had last seen a physician for
      acute illness. Of the 304, 256 (84.2%) preferred seeing their regular physicians
      during acute illness, and 48 (15.8%) did not. Of those who preferred seeing their
      regular physicians, 131 (51.2%) did see their regular physicians, 125 (48.8%) did
      not MAIN OUTCOME MEASURES: Preference for seeing regular physician and seeing
      regular physician during acute illness. RESULTS: Multiple logistic regression
      found that believing continuity of care was important and traveling further
      increased, while recent hospitalization and difficulty seeing physicians during
      or after office hours decreased, the likelihood of actually seeing their regular
      physicians. CONCLUSION: Almost half the patients who preferred seeing their
      regular physicians for acute illness did not actually see their regular
      physicians. Improving access to regular physicians might encourage patients to
      always try to see them.

PMID- 14649990
TI  - Which hand-held computer is better for doctors? Part 1: Comparing models with
      Palm operating systems.

PMID- 14649991
TI  - U.S. Navy sources and receivers for studying acoustic propagation and climate
      change in the ocean.

PMID- 14649992
TI  - Determination of transport parameters in air-saturated porous materials via
      reflected ultrasonic waves.
AB  - An ultrasonic reflectivity method of evaluating the acoustic parameters of porous
      materials saturated by air (or any other gas) is discussed. The method is based
      on experimental detection of waves reflected at normal incidence by the first and
      second interface of the material. This method is based on a temporal model of
      direct and inverse scattering problems for the propagation of transient
      ultrasonic waves in a homogeneous isotropic slab of porous material with a rigid
      frame [Fellah et al., J. Acoust. Soc. Am. 113, 61-73 (2003)]. Generally, the
      conventional ultrasonic approach can be used to determine tortuosity, and viscous
      and thermal characteristic lengths via transmitted waves. Porosity cannot be
      estimated in transmitted mode because of its very weak sensitivity. First
      interface use of the reflected wave at oblique incidence leads to the
      determination of porosity and tortuosity [Fellah et al., J. Acoust. Soc. Am. 113,
      2424-2433 (2003)] but this is not possible at normal incidence. Using
      experimental data of reflected waves by the first and second interface at normal
      incidence simultaneously leads to the determination of porosity, tortuosity,
      viscous and thermal characteristic lengths. As with the classic ultrasonic
      approach for characterizing porous material saturated with one gas, both
      characteristic lengths are estimated individually by assuming a given ratio
      between them. Tests are performed using weakly resistive industrial plastic
      foams. Experimental and numerical results, and prospects are discussed.

PMID- 14649993
TI  - Modified Szabo's wave equation models for lossy media obeying frequency power
      law.
AB  - Szabo's models of acoustic attenuation [Szabo, J. Acoust. Soc. Am. 96(1), 491-500
      (1994)] comply well with the empirical frequency power law involving noninteger
      and odd-integer exponent coefficients while guaranteeing causality, but
      nevertheless encounter the troublesome issues of hypersingular improper integral
      and obscurity in implementing initial conditions. The purpose of this paper is to
      ease or remove these drawbacks of the Szabo's models via the Caputo fractional
      derivative concept. The positive time-fractional derivative is also introduced to
      include the positivity of the attenuation processes.

PMID- 14649994
TI  - Locally conformal method for acoustic finite-difference time-domain modeling of
      rigid surfaces.
AB  - The finite-difference time-domain method is a simple but powerful numerical
      method for simulating full-wave acoustic propagation and scattering. However, the
      method can demand a large amount of computational resources. Traditionally,
      continuously curved boundaries are represented in a stair-step fashion and thus
      accurately modeling scattering from a boundary will require a finer
      discretization than would otherwise be necessary for modeling propagation in a
      homogeneous medium. However, a fine discretization might not be practical due to
      limited computational resources. A locally conformal technique is presented here
      for modeling acoustic scattering from continuously curved rigid boundaries. This
      technique is low cost, simple to implement, and gives better results for the same
      grid discretization than the traditional stair-step representation. These
      improvements can be traded for a coarser discretization which reduces the
      computational burden. The improved accuracy of this technique is demonstrated for
      a spherical scatterer.

PMID- 14649995
TI  - Ultrasonic wave interaction with multidirectional composites: modeling and
      experiment.
AB  - Phenomena of wave transmission through a multidirectional composite laminate
      immersed in a fluid have been investigated. Based on a recently-developed
      recursive stiffness matrix method time-domain beam models have been developed to
      simulate the problem. Experimental and theoretical results at frequency 2.25 MHz
      show that the transmission amplitude is highly dependent on lamina orientation
      and angle of incidence. Large transmission amplitude appears at small (<10
      degrees) and large incident angles (45 degrees-60 degrees). At intermediate
      incident angles (16 degrees-40 degrees) the transmission amplitude is almost
      zero. At high frequency, the residue epoxy layers between each lamina become
      important and corresponding resonances may be observed. These transmission
      phenomena have been interpreted in terms of Floquet waves. It shows that the pass
      and stop bands of the three Floquet waves obtained from the unit cell stiffness
      matrix determine the transmission amplitude distribution in frequency, incident
      angle and rotation angle domains. The effect of random deviation of the laminated
      structure periodicity has also been assessed. At normal incidence, the variation
      of the thickness of the epoxy residual layer between composite lamina has little
      effect on the overall stop and pass band structures but introduces random
      reverberation and scattering in the pass bands. It is shown that for oblique
      incidence the transmittivity spectrum of a composite with random lamina lay-up
      converges with increase of randomness to that of a [0/-45/90/45]2s quasi
      isotropic composite. Randomization of lamina lay-up produces a small effect in
      the transmittivity spectrum for a quasi-isotropic composite.

PMID- 14649996
TI  - Capillary forces in the acoustics of patchy-saturated porous media.
AB  - A linearized theory of the acoustics of porous elastic formations, such as rocks,
      saturated with two different viscous fluids is generalized to take into account a
      pressure discontinuity across the fluid boundaries. The latter can arise due to
      the surface tension of the membrane separating the fluids. We show that the
      frequency-dependent bulk modulus K(omega) for wavelengths longer than the
      characteristic structural dimensions of the fluid patches has a similar analytic
      behavior to the case of a vanishing membrane stiffness and depends on the same
      parameters of the fluid-distribution topology. The effect of the capillary
      stiffness can be accounted for by renormalizing the coefficients of the leading
      terms in the low-frequency limit of K(omega).

PMID- 14649997
TI  - Investigation of the convergence of the mixed displacement-pressure formulation
      for three-dimensional poroelastic materials using hierarchical elements.
AB  - Recently, a mixed pressure displacement [u, P] formulation based on Biot's
      poroelasticity equations has been presented for porous materials. This model
      leads to a reduction of the number of degrees of freedom required for the
      modeling of three-dimensional porous media in comparison to classical
      displacement-displacement [u, U] formulations. In this paper, an extension of the
      [u, P] formulation based on hierarchical elements is presented. First, a variant
      of the weak integral form of the [u, P] formulation is presented and its
      numerical implementation using hierarchical elements is detailed, together with
      the application of boundary and loading conditions. Numerical results are
      presented to show the accuracy and performance of the present approach. In
      particular, the importance of correctly capturing the coupling effects between
      the two phases is highlighted.

PMID- 14649998
TI  - Elastic constants of layers in isotropic laminates.
AB  - The individual laminae elastic constants in multilayer laminates composed of
      dissimilar isotropic layers were determined using ultrasonic-resonance
      spectroscopy and the linear theory of elasticity. Ultrasonic resonance allows one
      to measure the free-vibration response spectrum of a traction-free solid under
      periodic vibration. These frequencies depend on pointwise density, laminate
      dimensions, layer thickness, and layer elastic constants. Given a material with
      known mass but unknown constitution, this method allows one to extract the
      elastic constants and density of the constituent layers. This is accomplished by
      measuring the frequencies and then minimizing the differences between these and
      those calculated using the theory of elasticity for layered media to select the
      constants that best replicate the frequency-response spectrum. This approach is
      applied to a three-layer, unsymmetric laminate of WpCu, and very good agreement
      is found with the elastic constants of the two constituent materials.

PMID- 14649999
TI  - Basic types of discontinuity in circular acoustic wave guide.
AB  - It is considered the interaction of acoustic waves with two basic discontinuities
      -"diameter step" and "diaphragm with coaxial opening"--in a cylindrical acoustic
      waveguide with a rigid wall. The problem is considered and solved in rigorous
      formulation for the case of axial symmetry and below first radial resonance
      (f(r1)) in the waveguide. Obtained data demonstrate that a one-dimensional (1-D)
      model provides good results for the "diameter step" if the frequency does not
      exceed 18%-50% of f(r1). Calculated data for the "diameter step" demonstrate that
      this discontinuity follows the reciprocity principle (below f(r1))--the parameter
      of nonreciprocity does not exceed calculation errors. Data for the "diaphragm"
      demonstrate good agreement with the Lamb formula for a rigid screen with parallel
      slots--a 2-D problem in the Cartesian coordinates. Calculation errors for the
      both discontinuities were evaluated with the energy conservation law. The
      difference between sum of power fluxes in reflected and transmitted waves and the
      power flux in the incident wave does not exceed 1%.

PMID- 14650000
TI  - Unidimensional models of acoustic propagation in axisymmetric waveguides.
AB  - This paper presents a model of the linear acoustic propagation in axisymmetric
      waveguides, the pressure depending on a single space variable. The approach
      consists of writing the wave equation and the boundary conditions for a
      coordinate system rectifying the isobaric map at each time. The two-dimensional
      dependence of the problem is thus transferred from the pressure to the
      coefficients of the wave equation. From this result, an exclusively geometrical
      necessary condition is deduced for the admissibility of isobaric maps. However,
      the knowledge of the waveguide geometry is not sufficient to separate the
      pressure and the isobaric map solutions. In order to develop a unidimensional
      wave equation, a geometrical hypothesis is discussed. For lossless and motionless
      rigid waveguides, the deduced equation leads to exact results for tubes and
      cones. It may be interpreted as a Webster equation for a particular coordinate
      system so that the particular profiles for which analytical solutions of the
      pressure exist are redefined. The wave equation is also established for pipes
      with visco-thermal losses and, more generally, for mobile walls having a small
      admittance. The compatibility of the geometrical hypothesis with the exact model
      is specified for this general case.

PMID- 14650001
TI  - Detection of object resonances by vibro-acoustography and numerical vibrational
      mode identification.
AB  - Chalk sphere and cylinder resonance frequencies related to compressional and
      bending modes were detected in water, using vibro-acoustography, a relatively new
      imaging technique. The variable (radiation) force of low-frequency excitation,
      produced by intersecting two primary focused ultrasound waves with slightly
      different frequencies, forces the object to vibrate. The low-frequency acoustic
      emission field, resulting from object vibration, was detected by a hydrophone. By
      fixing the object at the focus of the ultrasound beam and sweeping the frequency
      of one of the primary beams within a chosen bandwidth, it was possible to detect
      some of the resonance frequencies (those related to compressional and bending
      modes) via variations in acoustic emission amplitude. Experimental results showed
      excellent agreement with finite element calculations. This method can be used to
      characterize the presence of heterogeneities in various media, in the field of
      materials science or biology.

PMID- 14650002
TI  - The selection of layer thicknesses to control acoustic radiation force profiles
      in layered resonators.
AB  - Ultrasonic standing waves can be used to generate radiation forces on particles
      within a fluid. A number of authors have derived detailed representations of
      these forces but these are most commonly applied using an approximation to the
      energy distribution based upon an idealized standing wave within a mode based
      upon rigid boundaries. An electro-acoustic model of the acoustic energy
      distribution within a standing wave with arbitrary thickness boundaries has been
      expanded to model the radiation force on an example particle within the acoustic
      field. This is used to examine the force profile on a particle at resonances
      other than those predicted with rigid boundaries, and with pressure nodes at
      different positions. A simple analytical method for predicting modal conditions
      for combinations of frequencies and layer thickness characteristics is presented,
      which predicts that resonances can exist that will produce a pressure node at
      arbitrary positions in the fluid layer of such a system. This can be used to
      design resonators that will drive particles to positions other than the center of
      the fluid layer, including the fluid/solid boundary of the layer, with
      significant potential applications in sensing systems. Further, the model also
      predicts conditions for multiple subwavelength resonances within the fluid layer
      of a single resonator, each resonance having different nodal planes for particle
      concentration.

PMID- 14650003
TI  - The ultrasonic weak short-pulse responses of microbubbles based on a two
      frequency approximation.
AB  - The ultrasonic short-pulse responses of microbubbles are of interest in
      cavitation, transient responses, and contrast imaging. We extend the two
      frequency analytic solutions of Newhouse and Shankar [J. Acoust. Soc. Am. 75,
      1473-1477 (1984)] to approximate the short-pulse responses of microbubbles in a
      low-amplitude field. Based on their results, there is an expected component near
      dc in the spectrum of bubble echoes excited by a short pulse. Here this component
      is named the low-frequency response, and its theoretical properties are verified
      experimentally. Including the fundamental and second-harmonic components, the
      weak short-pulse responses of microbubbles include three types of response. Our
      work has determined the constraint conditions under which this approximated
      solution can be used to analyze these short-pulse responses. This paper also
      provides the amplitude and spectral properties of these responses. The low
      frequency response has a special bandwidth-dependent property and has potential
      applications in imaging and bubble sizing.

PMID- 14650004
TI  - Measurements of near-surface bubble plumes in the open ocean with implications
      for high-frequency sonar performance.
AB  - This study examines near-surface bubble data obtained with a self-contained 200
      kHz inverted echo-sounder deployed at Ocean Station Papa (NE Pacific, 1400 km
      west of Vancouver Is.) over an 81-day period in the spring of 1996. The
      instrument operated continuously, recording calibrated volume scattering profiles
      from near-surface bubbles with 3-s and 30-cm resolution. The data show the
      frequent occurrence of bubbles organized into vertical, plume-like structures,
      presumably drawn downwards by turbulence and other near-surface circulations.
      Average bubble plume penetrations of up to 15 m were observed, with maximum
      penetrations up to 25 m. Within the plumes, the backscatter cross section
      exhibited an exponential decay with depth, with e-folding scale in the range 0.5
      to 3 m, increasing proportionally to the square of average plume depth. Using
      standard models for bubble scattering, and incorporating recent acoustic
      resonator measurements of bubble-size distributions along with actual bubble
      plume data, high-frequency near-surface sonar performance models were developed.
      These models show that on a ping-to-ping basis the bubble plume structures can
      induce significant spatial variations in the reverberation level and path
      integrated extinction losses to near-surface targets.

PMID- 14650005
TI  - High-frequency acoustic scattering from turbulent oceanic microstructure: the
      importance of density fluctuations.
AB  - Acoustic scattering techniques provide a unique and powerful tool to remotely
      investigate the physical properties of the ocean interior over large spatial and
      temporal scales. With high-frequency acoustic scattering it is possible to probe
      physical processes that occur at the microstructure scale, spanning submillimeter
      to centimeter scale processes. An acoustic scattering model for turbulent oceanic
      microstructure is presented in which the current theory, which only accounts for
      fluctuations in the sound speed, has been extended to include fluctuations in the
      density as well. The inclusion of density fluctuations results in an expression
      for the scattering cross section per unit volume, sigma(v), that is explicitly
      dependent on the scattering angle. By relating the variability in the density and
      sound speed to random fluctuations in oceanic temperature and salinity, sigma(v)
      has been expressed in terms of the temperature and salinity wave number spectra,
      and the temperature-salinity co-spectrum. A Batchelor spectrum for temperature
      and salinity, which depends on parameters such as the dissipation rates of
      turbulent kinetic energy and temperature variance, has been used to evaluate
      sigma(v). Two models for the temperature-salinity co-spectrum have also been
      used. The predictions indicate that fluctuations in the density could be as
      important in determining backscattering as fluctuations in the sound speed. Using
      data obtained in the ocean with a high resolution vertical microstructure
      profiler, it is predicted that scattering from oceanic microstructure can be as
      strong as scattering from zooplankton.

PMID- 14650006
TI  - Changes in volume reverberation from deep to shallow water in the eastern Gulf of
      Mexico.
AB  - Scattering from fish is a primary cause of volume reverberation and, since fish
      populations change from deep to shallow water, the character of volume
      reverberation should also change. However, there are few data available to
      document expected changes. Therefore, an experiment was conducted in the eastern
      Gulf of Mexico to investigate possible changes in volume reverberation from deep
      to slope to shelf waters. Results showed that volume reverberation in outer shelf
      waters varied more rapidly with respect to both time and space than that in
      deeper waters. Day-time scattering was similar for deep, slope and shelf waters,
      total scattering strengths generally increased with frequency. Night-time
      scattering for the deep ocean and slope also increased with increasing frequency.
      Scattering modeling suggests that swimbladder-bearing fishes smaller than 10 cm
      were responsible for the observed volume reverberation. Night-time scattering at
      the outer shelf location was very different, with strong scattering peaks at low
      frequencies. Scattering modeling implicates 12-15 cm rough scad and round herring
      as potential causes of the low frequency peaks. Hence, experiment results
      confirmed that, as expected, volume reverberation over shelf waters is different
      and more variable than in deeper waters of the eastern Gulf of Mexico.

PMID- 14650007
TI  - Time-dependent seafloor acoustic backscatter (10-100 kHz).
AB  - A time-dependent model of the acoustic intensity backscattered by the seafloor is
      described and compared with data from a calibrated, vertically oriented, echo
      sounder operating at 33 and 93 kHz. The model incorporates the characteristics of
      the echo-sounder and transmitted pulse, and the water column spreading and
      absorption losses. Scattering from the water-sediment interface is predicted
      using Helmholtz-Kirchhoff theory, parametrized by the mean grain size, the
      coherent reflection coefficient, and the strength and exponent of a power-law
      roughness spectrum. The composite roughness approach of Jackson et al. [J.
      Acoust. Soc. Am. 79, 1410-1422 (1986)], modified for the finite duration of the
      transmitted signal, is used to predict backscatter from subbottom
      inhomogeneities. It depends on the sediment's volume scattering and attenuation
      coefficients, as well as the interface characteristics governing sound
      transmission into the sediment. Estimation of model parameters (mean grain size,
      roughness spectrum strength and exponent, volume scattering coefficient) reveals
      ambiguous ranges for the two spectral components. Analyses of model outputs and
      of physical measurements reported in the literature yield practical constraints
      on roughness spectrum parameter settings appropriate for echo-envelope-based
      sediment classification procedures.

PMID- 14650008
TI  - Remote sensing of sediment characteristics by optimized echo-envelope matching.
AB  - A sediment geoacoustic parameter estimation technique is described which compares
      bottom returns, measured by a calibrated monostatic sonar oriented within 15
      degrees of vertical and having a 10 degree-21 degree beamwidth, with an echo
      envelope model based on high-frequency (10-100 kHz) incoherent backscatter theory
      and sediment properties such as: mean grain size, strength, and exponent of the
      power law characterizing the interface roughness energy density spectrum, and
      volume scattering coefficient. An average echo envelope matching procedure
      iterates on the reflection coefficient to match the peak echo amplitude and
      separate coarse from fine-grain sediments, followed by a global optimization
      using a combination of simulated annealing and downhill simplex searches over
      mean grain size, interface roughness spectral strength, and sediment volume
      scattering coefficient. Error analyses using Monte Carlo simulations validate
      this optimization procedure. Moderate frequencies (33 kHz) and orientations
      normal with the interface are best suited for this application. Distinction
      between sands and fine-grain sediments is demonstrated based on acoustic
      estimation of mean grain size alone. The creation of feature vectors from
      estimates of mean grain size and interface roughness spectral strength shows
      promise for intraclass separation of silt and clay. The correlation between
      estimated parameters is consistent with what is observed in situ.

PMID- 14650009
TI  - Closed-form expressions for ocean reverberation and signal excess with mode
      stripping and Lambert's law.
AB  - Closed-form expressions for two-way propagation and reverberation in variable
      depth ducts are derived for isovelocity water by using ray invariants and
      acoustic flux. These expressions include the transition to single mode
      propagation at long range. Three surface scattering laws are considered: Lambert,
      Lommel-Seeliger, and angle independent, and these are compared with a point
      target to give explicit signal-to-reverberation ratios. In particular, there is
      interesting and sometimes surprising behavior when the propagation obeys mode
      stripping (the high angles are preferentially attenuated by bottom losses) whilst
      the scattering obeys Lambert's law (high angles are preferentially back
      scattered). There may be conditions where the signal-to-reverberation ratio is
      independent of range so that there is no reverberation range limit. Bottom slope
      dependence of both target echo and reverberation is surprisingly weak. The
      implications of refraction are discussed. The angle dependence for a point or
      surface scatterer at a given range can be translated into arrival time, so it is
      possible to calculate the received pulse shape for one-way or two-way paths.
      Because the tail is exponential with a range-independent half-life that only
      depends on bottom reflection properties there is scope for extracting geoacoustic
      information from the pulse shape alone. This environmental time spread is also of
      use to sonar designers.

PMID- 14650010
TI  - Acoustic backscattering by Hawaiian lutjanid snappers. 1. Target strength and
      swimbladder characteristics.
AB  - The target strengths and swimbladder morphology of six snapper species were
      investigated using broadband sonar, x rays, and swimbladder casts. Backscatter
      data were obtained using a frequency-modulated sweep (60-200 kHz) and a
      broadband, dolphinlike click (peak frequency 120 kHz) from live fish, mounted and
      rotated around each of their three axes. X rays revealed species-specific
      differences in the shape, size, and orientation of the swimbladders. The angle
      between the fish's dorsal aspect and the major axis of its swimbladder ranged
      from 3 degrees to 12 degrees and was consistent between individuals within a
      species. This angle had a one-to-one relationship with the angle at which the
      maximum dorsal aspect target strength was measured (r2 = 0.93), regardless of
      species. Maximum dorsal aspect target strength was correlated with length within
      species. However, the swimbladder modeled as an air-filled prolate spheroid with
      axes measured from the x rays of the swimbladder predicted maximum target
      strength significantly better than models based on fish length or swimbladder
      volume. For both the dorsal and lateral aspects, the prolate spheroid model's
      predictions were not significantly different from the measured target strengths
      (observed power >0.75) and were within 3 dB of the measured values. This model
      predicts the target strengths of all species equally well, unlike those based on
      length.

PMID- 14650011
TI  - Acoustic backscattering by Hawaiian lutjanid snappers. II. Broadband temporal and
      spectral structure.
AB  - The characteristics of acoustic echoes from six species of deep-dwelling (up to
      400 m) Hawaiian Lujanid snappers were determined by backscatter measurements at
      the surface. A broadband linear frequency-modulated signal and a short
      dolphinlike sonar signal were used as the incident signals. The fish were
      anesthetized and attached to a monofilament net that was attached to a rotor so
      echoes could be collected along the roll, tilt, and lateral axes of each fish.
      The temporal highlight structure of broadband echoes was determined by
      calculating the envelope of the cross-correlation function between the incident
      signal and the echoes. The echo waveforms were complex with many highlights and
      varied with the orientation of the fish. In the tilt plane, the strongest echoes
      occurred when the incident signal was perpendicular to the long axis of the
      swimbladder. The number of highlights was the fewest at this orientation. The
      number of echo highlights and the length of echoes increased as the fish was
      tilted from this orientation. The highlight structure of the echoes resulted in
      the transfer function being rippled, with local maxima and minima that changed
      with fish size and species. The echo structures in both the time and frequency
      domains were generally consistent within species and were easily distinguishable
      between species.

PMID- 14650012
TI  - Theory of explosive beam spreading due to ray chaos.
AB  - In an ocean acoustic situation where rays are known to be chaotic, a theory based
      on a Gaussian beam approximation is used to show that the width of a narrow-angle
      beam increases exponentially (explosively) with range at a rate that is given by
      the Lyapunov exponent that is calculated in the geometric limit. This finite
      frequency result shows that the phenomenon of "wave chaos" is real, and might be
      observable experimentally.

PMID- 14650013
TI  - Finite-bandwidth effects on the causal prediction of ultrasonic attenuation of
      the power-law form.
AB  - Kramers-Kronig (K-K) relations exist as a consequence of causality, placing
      nonlocal constraints on the relationship between dispersion and absorption. The
      finite-bandwidth method of applying these relations is examined where the K-K
      integrals are restricted to the spectrum of the experimental data. These finite
      bandwidth K-K relations are known to work with resonant-type data and here are
      applied to dispersion data consistent with a power-law attenuation coefficient
      (exponent from 1 to 2). Bandwidth-restricted forms of the zero and once
      subtracted K-K relations are used to determine the attenuation coefficient from
      phase velocity. Analytically, it is shown that these transforms produce the
      proper power-law form of the attenuation coefficient as a stand-alone term summed
      with artifacts that are dependent on the integration limits. Calculations are
      performed to demonstrate how these finite-bandwidth artifacts affect the K-K
      predictions under a variety of conditions. The predictions are studied in a local
      context as a function of subtraction frequency, bandwidth, and power-law
      exponent. The K-K predictions of the power-law exponent within various decades of
      the spectrum are also examined. In general, the agreement between finite
      bandwidth K-K predictions and exact values grows as the power-law exponent
      approaches 1 and with increasing bandwidth.

PMID- 14650014
TI  - Open cycle traveling wave thermoacoustics: mean temperature difference at the
      regenerator interface.
AB  - In an open cycle traveling wave thermoacoustic engine, the hot heat exchanger is
      replaced by a steady flow of hot gas into the regenerator to provide the thermal
      energy input to the engine. The steady-state operation of such a device requires
      that a potentially large mean temperature difference exist between the incoming
      gas and the solid material at the regenerator's hot side, due in part to
      isentropic gas oscillations in the open space adjacent to the regenerator. The
      magnitude of this temperature difference will have a significant effect on the
      efficiencies of these open cycle devices. To help assess the feasibility of such
      thermoacoustic engines, a numerical model is developed that predicts the
      dependence of the mean temperature difference upon the important design and
      operating parameters of the open cycle thermoacoustic engine, including the
      acoustic pressure, mean mass flow rate, acoustic phase angles, and conductive
      heat loss. Using this model, it is also shown that the temperature difference at
      the regenerator interface is approximately proportional to the sum of the
      acoustic power output and the conductive heat loss at this location.

PMID- 14650015
TI  - Vibration of prolate spheroidal shells with shear deformation and rotatory
      inertia: axisymmetric case.
AB  - This paper presents the derivation of the equations for nonaxisymmetric motion of
      prolate spheroidal shells of constant thickness. The equations include the effect
      of distributed mechanical surface forces and moments. The shell theory used in
      this derivation includes three displacements and two thickness shear rotations.
      Thus, the effects of membrane, bending, shear deformation, and rotatory inertia
      are included in this theory. The resulting five coupled partial differential
      equations are self-adjoint and positive definite. The frequency-wave-number
      spectrum has five branches, two acoustic and three optical branches representing
      flexural, extensional, torsional, and two thickness shear. For the case of
      axisymmetric motion, these were computed for various spheroidal shell
      eccentricities and thickness-to-length ratios for a large number of modes. The
      axisymmetric dynamic response for damped shells of various eccentricities and
      thicknesses under point and ring surface forces are presented.

PMID- 14650016
TI  - Structural acoustic silencers--design and experiment.
AB  - The effectiveness of introducing flexible structural layers into air conveying
      ducts for controlling noise is investigated through theoretical and experimental
      means, focusing at low frequencies where conventional passive silencing
      technology is least effective. Previous theoretical work has shown that using
      flexible rather than rigid walls has the potential to achieve high transmission
      losses. The physical mechanisms responsible for structural acoustic silencing,
      including the relation between transmission loss peaks and structural resonance
      corresponding to different transverse structural modes, are presented.
      Sensitivity of the performance to acoustic and structural boundary conditions is
      discussed. To eliminate radiated noise from these walls (breakout noise), a rigid
      walled cavity is introduced under the flexible plate. The challenge is to find
      means to reject plane waves in the two-duct system. Designs that overcome these
      issues and achieve appreciable transmission loss are investigated. Results based
      on three-dimensional finite element simulations are compared with experimental
      results.

PMID- 14650017
TI  - Contrast source inversion methods in elastodynamics.
AB  - In this paper a nonlinear inversion method is presented for determining the mass
      density of an elastic inclusion from the knowledge of how the inclusion scatters
      known incident elastic waves. The algorithm employed is an extension of the
      multiplicative regularized contrast source inversion method (MR-CSI) to
      elasticity. This method involves alternate determination of the mass density
      contrast and the contrast sources (the product of the contrast and the fields) in
      each iterative step. The simple updating schemes of the method allow the
      introduction of an extra regularization term to the cost functional as a
      multiplicative constraint. This so-called MR-CSI method (MR-CSI) has been proven
      to be very effective for the acoustic and electromagnetic inverse scattering
      problems. Numerical examples demonstrate that the MR-CSI method shows excellent
      edge preserving properties by robustly handling noisy data very well, even for
      more complicated elastodynamic problems.

PMID- 14650018
TI  - Multiple bursts, multiple looks, and stream coherence in the release from
      informational masking.
AB  - In the simultaneous multitone masking paradigm introduced by Neff and Green
      [Percept. Psychophys. 41, 409-415 (1987)] the masker typically is a small number
      of tones having frequencies and levels that are randomly drawn on every
      presentation. Large amounts of masking for a pure-tone signal often occur that
      are thought to reflect central, rather than peripheral, limitations on
      processing. Previous work from this laboratory has indicated that playing a rapid
      succession of randomly drawn multitone maskers in each observation interval
      dramatically reduces the amount of masking that is observed relative to a single
      burst (SB). In this multiple-bursts-different (MBD) procedure, the signal tone is
      the only constant frequency component during the sequence of bursts and tends to
      perceptually segregate from the masker. In this study, the number of masker
      bursts and the interburst interval (IBI) were varied. The goals were to determine
      how the release from masking relative to the SB condition depends on the number
      of bursts and to examine whether increasing the IBI would cause each burst to be
      processed independently. If the latter were true, it might disrupt the perception
      of signal stream coherence, thereby diminishing the MBD advantage. However,
      multiple independent looks could also lead to an improvement in performance. For
      those subjects showing large amounts of informational masking in the SB
      condition, substantial reduction in masked thresholds occurred as the number of
      masker bursts increased, while masking increased as IBI lengthened. The results
      were not consistent with a simple version of a multiple-look model in which the
      information from each burst was combined optimally, but instead appear to be
      attributable to mechanisms involved in the perceptual organization of sounds.

PMID- 14650019
TI  - Interactions between test- and inducer-tone durations in induced loudness
      reduction.
AB  - A tone usually declines in loudness when preceded by a more intense inducer tone.
      This phenomenon is called "loudness recalibration" or "induced loudness
      reduction" (ILR). The present study investigates how ILR depends on level,
      loudness, and duration. A 2AFC procedure was used to obtain loudness matches
      between 2500-Hz comparison tones and 500-Hz test tones at 60 and 70 dB SPL,
      presented with and without preceding 500-Hz inducer tones. For 200-ms test and
      comparison tones, the amount of ILR did not depend on inducer level (set at 80 dB
      SPL and above), but ILR was greater with 200- than with 5-ms inducers, even when
      both were equally loud. For 5-ms tones, ILR was as great with 5- as with 200-ms
      inducers and about as great as when test and inducer tones both lasted 200 ms.
      These results suggest that (1) neither the loudness nor the SPL of the inducer
      alone governs ILR, and (2) inducer duration must equal or exceed test-tone
      duration to yield maximal amounts of ILR. Further analysis indicates that the
      efferent system may be partly responsible for ILR of 200-ms test tones, but is
      unlikely to account for ILR of 5-ms tones.

PMID- 14650020
TI  - Spatial unmasking of nearby pure-tone targets in a simulated anechoic
      environment.
AB  - Detection thresholds were measured for different spatial configurations of 500-
      and 1000-Hz pure-tone targets and broadband maskers. Sources were simulated using
      individually measured head-related transfer functions (HRTFs) for source
      positions varying in both azimuth and distance. For the spatial configurations
      tested, thresholds ranged over 50 dB, primarily as a result of large changes in
      the target-to-masker ratio (TMR) with changes in target and masker locations.
      Intersubject differences in both HRTFs and in binaural sensitivity were large;
      however, the overall pattern of results was similar across subjects. As expected,
      detection thresholds were generally smaller when the target and masker were
      separated in azimuth than when they were at the same location. However, in some
      cases, azimuthal separation of target and masker yielded little change or even a
      small increase in detection threshold. Significant intersubject differences
      occurred as a result both of differences in monaural and binaural acoustic cues
      in the individualized HRTFs and of different binaural contributions to
      performance. Model predictions captured general trends in the pattern of spatial
      unmasking. However, subject-specific model predictions did not account for the
      observed individual differences in performance, even after taking into account
      individual differences in HRTF measurements and overall binaural sensitivity.
      These results suggest that individuals differ not only in their overall
      sensitivity to binaural cues, but also in how their binaural sensitivity varies
      with the spatial position of (and interaural differences in) the masker.

PMID- 14650021
TI  - Effects of reverberation on perceptual segregation of competing voices.
AB  - Two experiments investigated the effect of reverberation on listeners' ability to
      perceptually segregate two competing voices. Culling et al. [Speech Commun. 14,
      71-96 (1994)] found that for competing synthetic vowels, masked identification
      thresholds were increased by reverberation only when combined with modulation of
      fundamental frequency (F0). The present investigation extended this finding to
      running speech. Speech reception thresholds (SRTs) were measured for a male voice
      against a single interfering female voice within a virtual room with controlled
      reverberation. The two voices were either (1) co-located in virtual space at 0
      degrees azimuth or (2) separately located at +/-60 degrees azimuth. In experiment
      1, target and interfering voices were either normally intonated or resynthesized
      with a fixed F0. In anechoic conditions, SRTs were lower for normally intonated
      and for spatially separated sources, while, in reverberant conditions, the SRTs
      were all the same. In experiment 2, additional conditions employed inverted F0
      contours. Inverted F0 contours yielded higher SRTs in all conditions, regardless
      of reverberation. The results suggest that reverberation can seriously impair
      listeners' ability to exploit differences in F0 and spatial location between
      competing voices. The levels of reverberation employed had no effect on speech
      intelligibility in quiet.

PMID- 14650022
TI  - Blind estimation of reverberation time.
AB  - The reverberation time (RT) is an important parameter for characterizing the
      quality of an auditory space. Sounds in reverberant environments are subject to
      coloration. This affects speech intelligibility and sound localization. Many
      state-of-the-art audio signal processing algorithms, for example in hearing-aids
      and telephony, are expected to have the ability to characterize the listening
      environment, and turn on an appropriate processing strategy accordingly. Thus, a
      method for characterization of room RT based on passively received microphone
      signals represents an important enabling technology. Current RT estimators, such
      as Schroeder's method, depend on a controlled sound source, and thus cannot
      produce an online, blind RT estimate. Here, a method for estimating RT without
      prior knowledge of sound sources or room geometry is presented. The diffusive
      tail of reverberation was modeled as an exponentially damped Gaussian white noise
      process. The time-constant of the decay, which provided a measure of the RT, was
      estimated using a maximum-likelihood procedure. The estimates were obtained
      continuously, and an order-statistics filter was used to extract the most likely
      RT from the accumulated estimates. The procedure was illustrated for connected
      speech. Results obtained for simulated and real room data are in good agreement
      with the real RT values.

PMID- 14650023
TI  - A contribution to simulating a three-dimensional larynx model using the finite
      element method.
AB  - A three-dimensional model is presented to simulate the larynx during
      vocalization. The finite element method is used to calculate the airflow velocity
      and pressure along the larynx as well as tissue displacement. It is assumed that
      the larynx tissue is transversely isotropic and divided into three tissues:
      cover, ligament, and body. A contact-impact algorithm is incorporated to deal
      with the physics of the collision between both true vocal folds. The results show
      that the simulated larynx can reproduce the vertical and horizontal phase
      difference in the tissue movements and that the false vocal folds affect the
      pressure distribution over the larynx surfaces. The effects of exciting the
      larynx with different pressure drops are also investigated.

PMID- 14650024
TI  - Shaping function models of the phonatory excitation signal.
AB  - The phonatory excitation signal is the acoustic signal that is generated at the
      glottis by the vibrating vocal folds and pulsatile airflow. A shaping function
      model is a nonlinear memoryless input-output characteristic that transforms a
      simple harmonic into the desired output. The model can be fitted linearly to
      observed or simulated template cycles. The instantaneous values of the excitation
      cycle centroid, amplitude as well as length, and the cues for phonatory identity
      are set via distinct parameters. The synthetic phonatory excitation signal is
      zero on average, as well as identically zero when the glottal airflow rate is
      constant.

PMID- 14650025
TI  - Effects of fundamental frequency and vocal-tract length changes on attention to
      one of two simultaneous talkers.
AB  - Three experiments used the Coordinated Response Measure task to examine the roles
      that differences in F0 and differences in vocal-tract length have on the ability
      to attend to one of two simultaneous speech signals. The first experiment asked
      how increases in the natural F0 difference between two sentences (originally
      spoken by the same talker) affected listeners' ability to attend to one of the
      sentences. The second experiment used differences in vocal-tract length, and the
      third used both F0 and vocal-tract length differences. Differences in F0 greater
      than 2 semitones produced systematic improvements in performance. Differences in
      vocal-tract length produced systematic improvements in performance when the ratio
      of lengths was 1.08 or greater, particularly when the shorter vocal tract
      belonged to the target talker. Neither of these manipulations produced
      improvements in performance as great as those produced by a different-sex talker.
      Systematic changes in both F0 and vocal-tract length that simulated an
      incremental shift in gender produced substantially larger improvements in
      performance than did differences in F0 or vocal-tract length alone. In general,
      shifting one of two utterances spoken by a female voice towards a male voice
      produces a greater improvement in performance than shifting male towards female.
      The increase in performance varied with the intonation patterns of individual
      talkers, being smallest for those talkers who showed most variability in their
      intonation patterns between different utterances.

PMID- 14650026
TI  - Discrimination and identification of vowels by young, hearing-impaired adults.
AB  - This study examined the effects of mild-to-moderate sensorineural hearing loss on
      vowel perception abilities of young, hearing-impaired (YHI) adults. Stimuli were
      presented at a low conversational level with a flat frequency response
      (approximately 60 dB SPL), and in two gain conditions: (a) high level gain with a
      flat frequency response (95 dB SPL), and (b) frequency-specific gain shaped
      according to each listener's hearing loss (designed to simulate the frequency
      response provided by a linear hearing aid to an input signal of 60 dB SPL).
      Listeners discriminated changes in the vowels /I e E inverted-v ae/ when F1 or F2
      varied, and later categorized the vowels. YHI listeners performed better in the
      two gain conditions than in the conversational level condition. Performances in
      the two gain conditions were similar, suggesting that upward spread of masking
      was not seen at these signal levels for these tasks. Results were compared with
      those from a group of elderly, hearing-impaired (EHI) listeners, reported in
      Coughlin, Kewley-Port, and Humes [J. Acoust. Soc. Am. 104, 3597-3607 (1998)].
      Comparisons revealed no significant differences between the EHI and YHI groups,
      suggesting that hearing impairment, not age, is the primary contributor to
      decreased vowel perception in these listeners.

PMID- 14650027
TI  - The correlogram: a visual display of periodicity.
AB  - Fundamental frequency (F0) extraction is often used in voice quality analysis. In
      pathological voices with a high degree of instability in F0, it is common for F0
      extraction algorithms to fail. In such cases, the faulty F0 values might spoil
      the possibilities for further data analysis. This paper presents the correlogram,
      a new method of displaying periodicity. The correlogram is based on the waveform
      matching techniques often used in F0 extraction programs, but with no mechanism
      to select an actual F0 value. Instead, several candidates for F0 are shown as
      dark bands. The result is presented as a 3D plot with time on the x axis,
      correlation delay inverted to frequency on the y axis, and correlation on the z
      axis. The z axis is represented in a gray scale as in a spectrogram. Delays
      corresponding to integer multiples of the period time will receive high
      correlation, thus resulting in candidates at F0, F0/2, F0/3, etc. While the
      correlogram adds little to F0 analysis of normal voices, it is useful for
      analysis of pathological voices since it illustrates the full complexity of the
      periodicity in the voice signal. Also, in combination with manual tracing, the
      correlogram can be used for semimanual F0 extraction. If so, F0 extraction can be
      performed on many voices that cause problems for conventional F0 extractors. To
      demonstrate the properties of the method it is applied to synthetic and natural
      voices, among them six pathological voices, which are characterized by roughness,
      vocal fry, gratings/scrape, hypofunctional breathiness and voice breaks, or
      combinations of these.

PMID- 14650028
TI  - The dependency of timbre on fundamental frequency.
AB  - The dependency of the timbre of musical sounds on their fundamental frequency
      (F0) was examined in three experiments. In experiment I subjects compared the
      timbres of stimuli produced by a set of 12 musical instruments with equal F0,
      duration, and loudness. There were three sessions, each at a different F0. In
      experiment II the same stimuli were rearranged in pairs, each with the same
      difference in F0, and subjects had to ignore the constant difference in pitch. In
      experiment III, instruments were paired both with and without an F0 difference
      within the same session, and subjects had to ignore the variable differences in
      pitch. Experiment I yielded dissimilarity matrices that were similar at different
      F0's, suggesting that instruments kept their relative positions within timbre
      space. Experiment II found that subjects were able to ignore the salient pitch
      difference while rating timbre dissimilarity. Dissimilarity matrices were
      symmetrical, suggesting further that the absolute displacement of the set of
      instruments within timbre space was small. Experiment III extended this result to
      the case where the pitch difference varied from trial to trial. Multidimensional
      scaling (MDS) of dissimilarity scores produced solutions (timbre spaces) that
      varied little across conditions and experiments. MDS solutions were used to test
      the validity of signal-based predictors of timbre, and in particular their
      stability as a function of F0. Taken together, the results suggest that timbre
      differences are perceived independently from differences of pitch, at least for
      F0 differences smaller than an octave. Timbre differences can be measured between
      stimuli with different F0's.

PMID- 14650029
TI  - The structural dynamics of the American five-string banjo.
AB  - The American five-string banjo is unique among musical instruments in that many
      significant parameters that effect tone are easily adjusted. This is probably why
      so many banjo players fiddle with their banjo. The instrument is a combination of
      canonical vibrating systems (strings, and a circular membrane) and therefore more
      amenable to analysis and modeling than most other musical instruments (e.g., the
      violin). Such an analysis is presented here. The model is a harmonically driven
      string which excites the other strings and a membrane under tension, causing the
      membrane to radiate sound. Three figures-of-merit, FOMs, are assumed. They are
      loudness, brightness, and decay of the sound. The effects of a number of
      parameters on the proposed FOMs are investigated. Among these are the loss factor
      and tension of the membrane, the mass of the bridge, and the location on the
      string of the excitation. It is noted that the calculated effects of the changes
      agree with generally accepted setup practices.

PMID- 14650030
TI  - [Osteoporosis concerns everyone. A threat against public health which can be
      averted, according to the SBU-report].

PMID- 14650031
TI  - [Tuberculosis epidemic has reached Africa. HIV infection accelerates the risk of
      being infected, the BCG vaccine is not efficient enough].

PMID- 14650032
TI  - [Osteoporosis--prevention, diagnosis and treatment. A systematic literature
      review. SBU conclusions and summary].
AB  - A report by the Swedish Council on Technology Assessment in Health Care (SBU) has
      reviewed, classified, and graded the scientific literature on prevention,
      diagnosis and treatment of osteoporosis. This article summarizes the overall
      conclusions. There is no scientific evidence to support the use of bone density
      measurement as a screening method in healthy, middle-aged individuals. Patients
      with osteoporosis-related fractures are an undertreated group as regards
      pharmacotherapy and other interventions to prevent new fractures. There are some
      evidence that physical exercise to reduce falls among elderly and hip protectors
      can prevent fractures. The combination therapy of calcium and vitamin D is shown
      to reduce the risk for hip fractures and other fractures except vertebral
      fractures in elderly women. Bisphosphonates are shown to reduce the number of
      fractures, mainly vertebral fractures. SERM is shown to reduce the risk for
      vertebral fractures in postmenopausal women with osteoporosis. Important risk
      factors for osteoporosis-related fractures that can be treated are physical
      inactivity, low weight, tobacco smoking, high alcohol consumption, tendency to
      fall, impaired vision, low exposure to sunlight, and use of corticosteroids. No
      particular diagnostic method or measurement site is optimal for determining the
      risk for fracture in all parts of the skeleton. The various measurement methods-
      dual energy x-ray absorbtiometry (DXA), ultrasound (QUS), and computed tomography
      (QCT)--are not directly comparable.

PMID- 14650033
TI  - [Buruli ulcer--Africa's latest mycobacterial scourge].
AB  - Buruliulcer is an extensive ulceration usually on the extremities. The ulcer can
      spread to subcutaneous fat, muscle and even bone causing osteomyelitis and death.
      It is the the third most common mycobacterial disease in humans after
      tuberculosis and leprosy. The bacterium grows in still standing water and infects
      children through small ulcerations in their skin. Mycobacterium ulcerans may also
      be transmitted by the bite of aquatic bugs (Naucordiae), which harbor the
      bacterium in their salivary glands. The disease affects poor people in rural,
      tropical areas where deforestation has led to flooding rivers, stagnant bodies of
      water and marsh. Benin, Cote d'Ivoire and Ghana in West Africa are seriously hit.
      Skin transplantation is the treatment of choice. Treatment with antibiotics has
      been disappointing.

PMID- 14650034
TI  - [Time to stop testing adults for microhematuria].
AB  - This study compares recently published reports with earlier literature on
      asymptomatic microhematuria in order to determine which conditions we wish to
      diagnose using a dipstick, how effective the test is in a high risk population,
      which clinical significance a positive test result has as compared to a negative
      result, and which diagnostic value the test has in the workup of patients with
      urinary tract symptoms. The conclusion is that testing for microhematuria does
      not meet the requirements of a modern screening and diagnostic test. Better
      alternatives are presently available, and in the near future we will likely see
      urine tests for specific clinical conditions.

PMID- 14650035
TI  - [Result of a CPP-project at a primary health care center. Diabetes care in
      primary health care is resource-demanding].
AB  - Cost Per Patient (CPP) is a method to calculate health care costs for every
      individual health care contact. The method, which supplies information about
      diagnosis-related health care consumption, and was employed at the Primary Health
      Care Centre of Odeshog, Sweden. The study was conducted during 2001 and showed
      that 2% of the patients who had at least one contact with the health care centre
      were consuming 20% of the center's total resources. Furthermore, the single
      highest healthcare consumption was noted among the group of diabetic patients,
      mainly due to associated illness and the need for home care among those who were
      unable to manage their insulin injections themselves.

PMID- 14650036
TI  - [New treatment modalities for stroke in the near future].
AB  - The ischemic penumbra is a functionally depressed, structurally intact but
      potentially salvageable region in the brain following stroke. Several
      pathophysiological mechanisms dominate during various intervals after stroke
      onset. New promising clinical treatment possibilities include hemicraniectomy in
      younger patients with malignant media infarction (albeit no RCT data available as
      today); brain cooling during the acute phase; and constraint-induced therapy and
      physiotherapy enhanced either by psychotomimetics (amphetamine) to improve
      general function or by anesthesia of the shoulder and upper arm to improve
      chronic paretic hand function. In a further future perspective, promising results
      from animal experiments should be clinically translated. Such results include
      newborn neurons induced in the penumbra spontaneously after stroke (endogenous
      neurogenesis) or exogenously administered stem cells implanted directly, or
      alternatively migrating to the ischemic penumbra, where differentiation to
      functional neurons is hoped for. Several safety aspects are however crucial,
      especially with regard to minimizing the risk of tumorigenesis after application
      of exogenous stem cells, and further detailed experimental characterization is
      essential before large scale clinical trials are initiated.

PMID- 14650037
TI  - [The 60's anniversary of the Annual Meeting of the Swedish Medical Society. The
      flagship of the Medical Society in a perspective of the meeting's general].

PMID- 14650038
TI  - [The 60's anniversary of the Annual Meeting of the Swedish Medical Society. The
      Medical Society's manifestation of Swedish medicine].

PMID- 14650039
TI  - [Purr as a cat--and avoid osteoporosis].

PMID- 14650040
TI  - ["No one consults health services without reason". Only consumers' power with
      economical consequences can change health care].

PMID- 14650041
TI  - [The myth about the Tower of Babel or "Sic transit gloria mundi"].

PMID- 14650042
TI  - [The 2004 budget in the county of Stockholm hits against private practitioners].

PMID- 14650043
TI  - [A working group will present a suggestion concerning screening for colorectal
      cancer].

PMID- 14650044
TI  - [Significance of the clinical talk--a question of truth in every single case].

PMID- 14650045
TI  - [Thoughts in connection with some decisions by the HSAN].

PMID- 14650046
TI  - [Wrong about blood test in suspected appendicitis].

PMID- 14650047
TI  - [Yet (not)a taboo...]].

PMID- 14650048
TI  - [Aggression and power in psychiatry].

PMID- 14650049
TI  - [Tolerance and understanding in in alternative life styles].

PMID- 14650050
TI  - [Osteopathy helps in prevention and rehabilitation].

PMID- 14650051
TI  - [Nerve diseases of the aged in the sick-bed of children?].

PMID- 14650052
TI  - [When words disappear].

PMID- 14650053
TI  - [Public health in changing times].

PMID- 14650054
TI  - [Consequences of health care reform].

PMID- 14650056
TI  - [Diseases and its control on Dendrobium].
AB  - The diseases on the Dendrobium plants and their occurrence and damage as well as
      control methods have been investigated and studied. 11 kinds of fungi, 4 kinds of
      bacteria, 3 kinds of virus and one root-knot nematode were recorded. To control
      them effectively, cultural methods such as selecting cultivable field, keeping
      the field sanitation, enhancing cultural operations are mostly recommended. The
      application of chemical germicides is also stressed.

PMID- 14650055
TI  - [Study on organogenesis and dry substance accumulation of Bupleurum Chinense].
AB  - OBJECTIVE: To learn the development characteristics of Bupleurum chinese DC. and
      to provide the cultivation fundament. METHOD: Plant samples of different growing
      periods were collected and investigated. RESULTS: It was found that the
      development stages of B. chinense could be divided definitely into emergence of
      seedings, seedling, elongation of internode, flowering and fruiting, and
      dormancy. During its life, cotyledon, basal leaves and stem leaves appeared and
      died away in turn, and the stem extended to its full length in one month. The
      root reached its top length during seedling stage, and its diameter increased
      quickly from July to August. The dry substance accumulated in aerial part of the
      plant increased quickly, and that in root increased by 42.4%, 94.0%, or 40.1%
      respectively, from mid July to mid August after stem elongation beginning, from
      mid September to mid October, or from mid October to the date of harvesting.
      CONCLUSION: Management methods and planting technologies of B. chinense should be
      mapped out according to the different characteristics of its three key growing
      stages.

PMID- 14650057
TI  - [Studies on establishing rRNA gene map of Angelica sinensis and Rheum palmatum
      from Gansu by DNA sequencing].
AB  - OBJECTIVE: To amplify and sequence the internal transcripted spacer of rRNA gene
      of the seeds of Angelica sinensis and Rheum palmatum for establishing a new
      method to identify the Chinese herb seeds in molecular level. METHODS: rDNA in
      the seeds was extracted. Specific synthesized primers were applied to amplify the
      internal transcripted spacer of rRNA gene by nested PCR. And the PCR products
      were sequenced. RESULTS: PCR results were confirmed by agarose electrophoresis,
      the above-mentioned methods could achieve the PCR products of interval region of
      rRNA gene in the seeds, and the sequences of the internal transcripted spacer of
      rRNA gene in the seeds were acquired by sequencing. There existed marked
      difference. CONCLUSION: The base sequences of the internal transcripted spacer of
      rRNA gene in different plant Chinese seeds can be applied to be identifying
      marker in molecular level.

PMID- 14650058
TI  - [Application of chromatograph-digitized fingerprint spectrum in identification of
      indigenous medicinal materials Radix et Rhizoma Rhei from Gansu province].
AB  - OBJECTIVE: To establish HPLC-Digitized fingerprint spectrum (HPLC-DFPS) of Radix
      et Rhizoma Rhei from Gansu province. METHODS: HPLC method was applied. RESULTS
      AND CONCLUSION: A group of characteristic peaks suggested that HPLC-DFPS can be
      used for identification of Radix et Rhizoma Rhei from Gansu province.

PMID- 14650059
TI  - [Identification on Herba Hedyotidis by X-ray diffraction Fourier fingerprint
      pattern method].
AB  - OBJECTIVE: To establish a new identification and analysis method of Herba
      Hedyotidis. METHOD: Powder X-Ray diffraction fourier fingerprint pattern method.
      RESULT: Experiment and analysis were carried out on eight samples. The standard X
      Ray diffraction fourier fingerprint pattern method and characteristic diffraction
      peaks of Herba Hedyotidis were obtained. CONCLUSION: This method can be used for
      the identification of Herba Hedyotidis.

PMID- 14650060
TI  - [Effects of compound yi-zhi on learning and memory disorder and beta-amyloid
      protein induced neurotoxicity].
AB  - OBJECTIVE: To investigate the effects of Compound Yi-Zhi (CYZ) on learning and
      memory disorder and beta-amyloid protein induced neurotoxicity. METHODS: Various
      doses of CYZ were administered to SD rats for 8 days, twice a day. Then
      scopolamine hydrobrominde intraperitoneal injection was performed on each rat,
      and the MORRIS water maze test and step-though test were carried out respectively
      to explore the changes of the rats' learning and memory capacities. Primary rat
      cortex neurons were cultured in vitro for 7 days, and then serum containing CYZ
      was added to neurons before or after the addition of beta Amyloid peptide25-35 (A
      beta 25-35) to observe CYZ's protectiveness on neurotoxicity. MTT assay and test
      of level of LDH in the culture media were performed to achieve this aim. RESULTS:
      Compared with control group, in MORRIS water maze test time of finding the
      platform under the water surface decreased, and in step-though test the latent
      period rose and the error number got smaller. Moreover, in cultured primary
      neurons, the dramatic drop of LDH level in culture media and the high OD scores
      in MTT test indicated that CYZ could effectively resist the neurotoxicity induced
      by A beta 25-35. CONCLUSION: CYZ presented promising effects on learning and
      memory dysfunction and A beta-induced neurotoxicity in vitro.

PMID- 14650061
TI  - [Study on the effects of curcumin on angiogenesis].
AB  - OBJECTIVE: The effects of curcumin on angiogenesis were studied. METHODS:
      Proliferation of bovine aortic endothelial cells (BAECs) and cells of human
      cancerous cell line SGC-7901 were measured by MTT colorimetric assay after
      treated by various concentrations of curcumin. The effects of curcumin on BAECS
      proliferation promoted by tumor conditioned medium were observed by MTT
      colorimetric assay. The effects of various concentration of curcumin on the
      migration of BAECs and migration promoted by tumor conditioned medium were
      investigated by agorose assay. RESULTS: Curcumin can obviously inhibit the
      proliferation of BAECs induced by fetal bovine serum (FBS) and tumor conditioned
      medium. Curcumin can also obviously inhibit the migration of BAECs induced by FBS
      and tumor conditioned medium. CONCLUSION: Curcumin can inhibit angiogenesis by
      preventing proliferation and migration of endothelial cells. It also suggestes
      that curcumin is one kind of specific inhibitors of angiogenesis.

PMID- 14650062
TI  - [Study on preparation procedure of Suppositoria Radix Bupleuri for kids].
AB  - OBJECTIVE: To optimize the preparation procedure of Suppositoria Radix Bupleuri
      for Kids. METHODS: The extraction process and preparation procedure were studied
      by orthogonal experimental design. RESULTS: The extraction process was selected
      and suppositoria was prepared by hard fat. CONCLUSION: This preparation procedure
      is suitable.

PMID- 14650063
TI  - [Textual research of wuguteng].
AB  - OBJECTIVE: To make clear the origin of the traditional Chinese medicine,
      Wuguteng. METHODS: The correlation literature was consulted and arranged.
      RESULTS: There are a few plants using as Wuguteng, such as Fissistigma
      glaucescens (Hance) Merr. and Marsdenia tenacissima (Roxb.) Wight et Arn. in the
      records of principle literature. Wuguteng used as a drug was first recorded in
      "Dian Nan Ben Cao". The views of various persons in past dynasties on the
      efficacy of Wuguteng are unanimous. CONCLUSION: The paper has proved that
      Wuguteng comes from Marsdenia tenacissima of Asclepiadaceae.

PMID- 14650064
TI  - Golden rule and R-E-S-P-E-C-T encourage employee loyalty.

PMID- 14650065
TI  - Putting your money where your people are: investing in enduring success.

PMID- 14650066
TI  - Recruiting and retaining employees: critical issues for organizational leaders.

PMID- 14650067
TI  - 20 more ways to build employee loyalty.

PMID- 14650068
TI  - 21st century ushers in integrative medicine. But many questions remain about how
      the health care system will react.

PMID- 14650069
TI  - Integrative medicine clinic requires solid business plan.
AB  - This case study of an clinic in California reveals how difficult it can be to
      successfully integrate traditional medicine with alternative therapies. Take a
      look at the obstacles that must be overcome.

PMID- 14650070
TI  - Scared silent: the clash between malpractice lawsuits & expert testimony.
AB  - As the Bush administration pushes Congress to place a $250,000 cap on pain and
      suffering awards in medical malpractice lawsuits, other moves quietly afoot by
      state medical boards, state medical associations, and specialty societies may
      reduce liability insurance premiums by limiting the number of suits.

PMID- 14650071
TI  - Health care decision-support systems needed now.
AB  - The technology exists now for developing a "Health Care Web" that would greatly
      improve health care decision making and research. But leaders must first be
      willing to cooperate to build the system.

PMID- 14650072
TI  - Are human research subjects safe enough?

PMID- 14650073
TI  - Revenue cycle management--Part II.

PMID- 14650074
TI  - 11 ways to digitize health care of the future.

PMID- 14650075
TI  - CQO role offers broad leadership challenges.

PMID- 14650076
TI  - Strategic financial decision making is key to project support.

PMID- 14650077
TI  - SARS: a closer look at this emerging infectious agent.

PMID- 14650078
TI  - Prospective funding of general hospitals in Norway--incentives for higher
      production?
AB  - In Norway, a new system of Activity Based Financing (ABF) for general hospitals
      was introduced on a comprehensive basis in July 1997. The main purpose of the
      reform was to increase activity so that more patients could receive treatment
      more quickly without reducing the quality of care. In this paper we analyse
      whether the reform has had any significant effect using two different performance
      indicators: number of patients treated and production of DRG points (Diagnosis
      Related Group). We divide the hospitals into two groups: hospitals owned by
      counties that have adopted the ABF system, and hospitals owned by counties using
      other funding systems. The first group then becomes the experiment group, while
      the second serves as a comparison group. It is argued that fixed-effect models
      are suitable specifications for this evaluation study, handling selection bias
      and the influence of unobservable explanatory variables in a consistent manner.
      We find that the reform has had a significant effect on the number of patients
      treated and DRG points produced. The results are sensitive as to how the
      experiment and the comparison group are determined.

PMID- 14650079
TI  - Deductibles in health insurance: pay or pain?
AB  - We study a health-insurance market where individuals are offered coverage against
      both medical expenditures and losses in income due to illness. Individuals vary
      in their level of innate ability and their probability of falling ill. If there
      is private information about the probability of illness and an individual's
      innate ability is sufficiently low, we find that competitive insurance contracts
      yield screening partly in the form of co-payment, i.e., a deductible in pay, and
      partly in the form of reduced medical treatment, i.e., a deductible in pain.

PMID- 14650080
TI  - Hospital pricing reform in the public health care system--an empirical case study
      from Finland.
AB  - Finland's 1993 state subsidy reform encouraged hospital districts to determine
      their services as products and change their pricing from bed-day to case-based
      and fee-for-service types. The economic incentive in hospital production was
      investigated by exploring how different price types affected the use of lumbar
      discectomies, and hip and knee replacements. Procedure rates, pricing, need,
      demand and supply variables in 1991-1998 were analysed using panel data methods.
      Case-based prices increased lumbar discectomies about 8%. In hip replacement the
      effect was opposite (-11%). Only for knee replacements (1995-1998) did mixed fee
      for-service and bed-day prices significantly increase production (21%).

PMID- 14650081
TI  - Parameters of control when facing stochastic demand: a DEA approach applied to
      Bangladeshi vaccination sites.
AB  - An aim of vaccination programs is near-complete coverage. One method for
      achieving this is for health facilities providing these services to operate
      frequently and for many hours during each session. However, if vaccine vials are
      not fully used, the remainder is often discarded, considered as waste. Without an
      active appointment schedule process, there is no way for facility staff to
      control the stochastic demand of potential patients, and hence reduce waste. And
      yet reducing the hours of operation or number of sessions per week could hinder
      access to vaccination services. In lieu of any formal system of controlling
      demand, we propose to model the optimal number of hours and sessions in order to
      maximize outputs, the number and type of vaccines provided given inputs, using
      Data Envelopment Analysis (DEA). Inputs are defined as the amount of vaccine
      wastage and the number of full-time equivalent staff, size of the facility,
      number of hours of operation and the number of sessions. Outputs are defined as
      the number and type of vaccines aimed at children and pregnant women. This
      analysis requires two models: one DEA model with possible reallocations between
      the number of hours and the number of sessions but with the total amount of time
      fixed and one model without this kind of reallocation in scheduling. Comparing
      these two scores we can identify the "gain" that would be possible were the
      scheduling of hours and sessions modified while controlling for all other types
      of inefficiency. By modeling an output-based model, we maintain the objective of
      increasing coverage while assisting decision-makers determining optimal operating
      processes.

PMID- 14650082
TI  - Viscoelastic properties of a mixed culture biofilm from rheometer creep analysis.
AB  - The mechanical properties of mixed culture biofilms were determined by creep
      analysis using an AR1000 rotating disk rheometer. The biofilms were grown
      directly on the rheometer disks which were rotated in a chemostat for 12 d. The
      resulting biofilms were heterogeneous and ranged from 35 microns to 50 microns in
      thickness. The creep curves were all viscoelastic in nature. The close agreement
      between stress and strain ratio of a sample tested at 0.1 and 0.5 Pa suggested
      that the biofilms were tested in the linear viscoelastic range and supported the
      use of linear viscoelastic theory in the development of a constitutive law. The
      experimental data was fit to a 4-element Burger spring and dashpot model. The
      shear modulus (G) ranged from 0.2 to 24 Pa and the viscous coefficient (eta) from
      10 to 3000 Pa. These values were in the same range as those previously estimated
      from fluid shear deformation of biofilms in flow cells. A viscoelastic biofilm
      model will help to predict shear related biofilm phenomena such as elevated
      pressure drop, detachment, and the flow of biofilms over solid surfaces.

PMID- 14650083
TI  - Effect of different concentrations of ortho-phthalaldehyde on biofilms formed by
      Pseudomonas fluorescens under different flow conditions.
AB  - The effectiveness of different concentrations of ortho-phthalaldehyde (OPA) in
      controlling biofilms of Pseudomonas fluorescens formed on stainless steel slides,
      using flow cell reactors under laminar and turbulent flow, was investigated by
      determining the variation in mass and respiratory activity. The physical
      stability of the biofilm with and without exposure to OPA was studied in a
      rotating device as variation in the mass of the biofilm on the surface after
      exposure to different rotation velocities. The activity of OPA against bacterial
      suspended cultures was evaluated in the presence and absence of bovine serum
      albumin (BSA) in order to evaluate the interference of proteins on the activity
      of the biocide. The results showed that biofilms formed under different flow
      conditions had different properties and reacted differently after biocide
      application. Biofilms formed under laminar flow were more easily inactivated than
      those formed under turbulent conditions. However, OPA did not promote the
      detachment of biofilms from the surface. The exposure of biofilms to different
      shear stress conditions after OPA treatment enhanced removal from the surface,
      indicating that OPA may weaken the biofilm matrix. The biocide was more effective
      on suspended cells than on cells grown in biofilms. This fact may be explained by
      the reaction of the biocide with proteins of the polymeric matrix of the biofilm
      as suggested by the significant reduction of biocide action on suspended cells in
      the presence of BSA.

PMID- 14650084
TI  - Evaluation of brushes for removal of fouling from fouling-release surfaces, using
      a hydraulic cleaning device.
AB  - A portable hydraulic device has been developed for use in optimizing the design
      of brushes and cleaning units that may be employed to maintain fouling-release
      coatings. Laboratory tests showed that characteristics of experimental cleaning
      brushes, including bristle stiffness, density, and angle, significantly affected
      the shear and normal forces imparted to the surface and thus, to any encrusting
      organisms. The standoff distance between the cleaning unit and the surface also
      influenced the forces generated. The rate of rotation of the brush, however, had
      little effect on force. The hydraulic device, with its experimental brushes, can
      also be used to evaluate the cleanability of fouling-release surfaces in situ, or
      to assess wear of the coating system due to cleaning.

PMID- 14650085
TI  - Bacterial biofilm in seawater: cell surface properties of early-attached marine
      bacteria.
AB  - The development of antifouling strategies in seawater requires knowledge of the
      physico-chemical properties of the cell surfaces of early adherent bacteria. The
      hydrophilic, electrostatic and the Lewis acid-base cell surface properties of
      eleven marine bacteria were characterized. Although these bacteria adhered to a
      hydrophilic support immersed for 3 and 6 h, they presented various physico
      chemical properties. Eleven strains possessed a hydrophilic surface and five a
      hydrophobic surface. Although the majority of the bacteria presented an electron
      donating character, some could not generate Lewis acid-base interactions with the
      support. On the other hand, all strains possessed an isoelectric point ranging
      from 2.2 to 3.4 and were negatively charged at the pH of seawater. Hydrophilicity
      was a preponderant property among these bacteria, but other properties should not
      be ignored. The development of new antifouling paints must take account all the
      possible interaction levels used by the bacteria to adhere to an immersed
      surface.

PMID- 14650086
TI  - Individual and coupled effects of echinoderm extracts and surface hydrophobicity
      on spore settlement and germination in the brown alga Hincksia irregularis.
AB  - Marine substrata possess cues that influence the behavior of fouling organisms.
      Initial adhesion of fouling algal zoospores to surfaces is also theorized to
      depend primarily upon interactions between substrata and spore cell bodies and
      flagellar membranes. In an effort to identify cues and surface characteristics
      that influence spore settlement and early development, the effects of bioactive
      echinoderm extracts, surface charge, and surface hydrophobicity were examined
      individually and in tandem on zoospore settlement and germination in Hincksia
      irregularis. Experiments utilizing 96-well plastic culture plates confirmed that
      spore settlement and germination were significantly affected by surface charge
      and hydrophobicity as well as by echinoderm metabolites, both individually and in
      tandem. Spore settlement rates in the dark over 30 min were > 400% higher on
      hydrophobic surfaces than on positively and negatively charged surfaces. Spore
      germling numbers were > 300% higher on hydrophobic surfaces than on positively
      and negatively charged surfaces when spores were allowed to settle in the light
      for 30 min and the settled spores allowed to subsequently germinate for 24 h.
      Spore germling numbers were consistently > 25% higher on hydrophobic surfaces
      than on positively and negatively charged surfaces when equal numbers of spores
      were allowed to completely settle in the light and subsequently germinate for 24
      h. H. irregularis germ tube lengths were also significantly longer on positively
      charged plates than on negatively charged plates. All echinoderm extracts tested
      had significant effects on germination and settlement at levels below those of
      estimated ecological concentrations. Short-term (30 min) exposure and subsequent
      germination experiments indicated that higher concentrations of extracts had
      rapid toxic effects on algal spores. Synchronous effects of echinoderm extracts
      and plate charge upon spore settlement varied considerably and did not show a
      strong dose response relationship. Long-term (24 h) exposure of spores to
      echinoderm extracts had dosage dependent effects on germination and spore
      survival. The results of this study indicate that H. irregularis spores possess
      the capacity for complex responses to their environment, utilizing combined cues
      of surface charge, surface energy and biochemistry to determine where to settle
      and germinate. These responses may aid spores in the detection of suitable
      substrata and conditions for settlement in the marine environment.

PMID- 14650087
TI  - A new antifouling bioassay monitoring brown algal spore swimming behaviour in the
      presence of echinoderm extracts.
AB  - Epibiosis, the colonization of biogenic surfaces by epibiotic organisms such as
      bacteria, filamentous algae, and sessile invertebrates, poses a major threat to
      the fitness and survival of macroorganisms which could potentially be fouled.
      Fouling of artificial submerged structures can also cause severe economic
      problems, making the need for refined bioassays to determine the efficacy of
      potential antifouling compounds even more important. The aim of this study was to
      use the distinct swimming behaviour of zoospores of the fouling brown alga
      Hincksia irregularis to develop a new laboratory antifouling bioassay to test the
      effect of marine natural products. Spores were exposed to different
      concentrations of aqueous and organic extracts from body walls of sympatric
      echinoderms (Asteroidea: Luidia clathrata, Astropecten articulatus; Ophiuroidea:
      Astrocyclus caecilia). Computer-assisted motion analysis was used to distinguish
      between the straight and fast swimming movements of undisturbed spores (controls)
      and the helical and erratic swimming patterns of chemically irritated spores,
      using the quantitative parameters rate of direction change (RCD) and swimming
      speed (SPD). The ratio RCD/SPD of spore swimming paths at extract treatments
      compared to controls can be used to quantify the detrimental effect of echinoderm
      extracts. Echinoderm extracts had significant effects on spore swimming behaviour
      at concentrations three orders of magnitude lower than that present naturally in
      the echinoderm body walls (mg extract/dry weight echinoderm body wall).
      Comparative studies on spore settlement and germination under similar treatment
      conditions show that changes in spore swimming behaviour reflect decreased
      fitness and survivourship of algal spores. It is suggested that this bioassay can
      be used to screen potential antifouling extracts and compounds at very low
      concentrations, making this assay particularly suitable for detection of
      concentration dependent effects and for bioassay-guided fractionation of extracts
      to identify active compounds.

PMID- 14650088
TI  - Pulse disturbances to the colonization of hard-substrates and in situ
      determination of copper using diffusive gradients in thin-films (DGT):
      quantifying dose and response in the field.
AB  - Studies conducted in Port Philip Bay, Victoria, Australia are described that
      examined the effect of experimentally elevated copper concentrations on the
      recruitment of epifauna to settlement plates. Simultaneous measurement of the
      copper concentration using diffusive gradients in thin films (DGT) allowed direct
      comparisons to be made between the labile copper concentration measured at the
      settlement surface, and the biological effects observed. Copper concentrations
      created by the field dosing technique were between 20-30 micrograms l-1 for the
      first 2 d, but then dropped considerably for the following 4 d (3 micrograms l
      1), and were indistinguishable from background for the final 7 d. The first 2 d
      of a copper pulse reduced the recruitment of barnacles, ascidians, serpulid
      worms, an encrusting bryozoan, and didemnid ascidians. The impacts occurred
      despite the copper pulse being much less than published LC50 values for similar
      species. The impacts were no longer obvious by day 7 or 14, having been obscured
      by either high mortality of early settlers, or large settlement events that took
      place after day 2. Thus the greatest impact of the pollution event occurred
      during the period of highest toxicant concentration. The value of this study lies
      in the correlation of toxicity effects with bio-available metal concentrations
      under realistic (natural, in situ) conditions.

PMID- 14650089
TI  - Osteoarthritis. What therapies for this disease of many causes?
AB  - Osteoarthritis is a common and sometimes disabling disease. New directions in
      therapy include inhibitors of selective proteins and transplantation of cultured
      chondrocytes. At the present time, treatment continues to be in response to a
      patient's symptoms. Thus, the challenge to physicians is to devise individual
      treatment plans that safely maximize relief and preservation of joint function.

PMID- 14650090
TI  - Rheumatoid arthritis. Targeted interventions can minimize joint destruction.
AB  - Rheumatoid arthritis can cause joint erosion and deformity, pain, stiffness, and
      decreased function and range of motion. Early diagnosis is crucial to prevent
      permanent joint damage. In this article, Drs Williams and Fye discuss articular
      and extra-articular manifestations of rheumatoid arthritis as well as the
      evolving treatment approaches to this complex disease.

PMID- 14650091
TI  - Systemic lupus erythematosus. How to manage, when to refer.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease seen predominately in
      women between the ages of 20 and 40. Because the disease varies in severity and
      can affect major organ systems, patients should be monitored carefully for organ
      damage and medication toxicity. In this article, Drs Dall'Era and Davis review
      the diagnosis of SLE as well as its epidemiologic factors and clinical
      characteristics. The section on therapy constitutes a practical resource for
      primary care physicians who care for patients with SLE.

PMID- 14650092
TI  - New issues in bacterial meningitis in adults. Antibiotic resistance has
      complicated treatment.
AB  - The epidemiologic factors of bacterial meningitis, a serious disease that must be
      addressed with great urgency, have evolved dramatically in the last 25 years.
      Among both adults and children, multidrug-resistant Streptococcus pneumoniae has
      emerged as a clinical challenge and has greatly complicated the empirical
      management of this disease. In this article, the author focuses on new issues
      involving the epidemiologic factors, diagnosis, treatment, and prevention of
      bacterial meningitis in adults.

PMID- 14650093
TI  - Seizures and subcutaneous calcifications. Pseudehypoparathyroidism.

PMID- 14650094
TI  - Patient notes: Influenza.

PMID- 14650095
TI  - Ontario's 2003 West Nile virus public education campaign: was anybody listening?

PMID- 14650096
TI  - Update: adverse events following civilian smallpox vaccination--United States,
      2003.

PMID- 14650097
TI  - Pre-placement screening in international adoption.
AB  - BACKGROUND: The number of child adoptions from abroad is increasing, but the
      adverse living conditions of these children prior to the adoption raise questions
      on their medical and neurodevelopmental status, particularly since there are no
      guidelines for pre- or post-adoption medical evaluation. OBJECTIVES: To describe
      the condition of a cohort of young children who were candidates for adoption in
      East European orphanages and foster homes, and to determine those attributes
      associated with a family's decision to adopt or refuse a particular child.
      METHODS: Eighty-two young children, median age 11 months, were evaluated by
      Israeli pediatricians in Eastern Europe between 3 weeks and 6 months prior to
      their adoption. The evaluation consisted of comprehensive medical and
      neurodevelopmental testing on site using a battery of standardized assessment
      tools, and observation of free play and social interactive behaviors recorded on
      videotape. Laboratory tests included complete blood count, chemistries, serology
      screening, and metabolic and genetic testing. RESULTS: The children were growth
      retarded. Medical problems were classified as resolved (pneumonia and diarrhea)
      in 32.8%; or ongoing, such as hepatitis B and C, failure to thrive, organomegaly,
      and visual and hearing disorders, in 14.8%. Neuromotor status was grossly
      abnormal in 13.4%. Twenty-two percent of the children were rejected for adoption
      by families in Israel. Factors associated with the adoption decision were
      performance skills on developmental testing (P = 0.0001), present medical status
      (P = 0.002), and weight (P = 0.016). CONCLUSIONS: Pre-placement comprehensive
      screening of children eligible for foreign adoption, which includes developmental
      screening, helps to identify a wide variety of strengths and impairments in a
      child's background before the adoption procedure is finalized. A family's
      decision to adopt or not was associated with the child's performance on Bayley
      Scales, weight, and current medical status, but not with language delays, serious
      past medical history or suspect family background.

PMID- 14650098
TI  - Vaginal colonization by orally administered Lactobacillus rhamnosus GG.
AB  - BACKGROUND: The lack of lactobacilli in the vagina of postmenopausal women due to
      estrogen deficiency plays an important role in the development of bacteriuria. In
      the last few years the use of lactobacilli for the prevention of genitourinary
      infections has been explored using different probiotic strains. OBJECTIVES: To
      evaluate the vaginal colonization by Lactobacillus rhamnosus GG in postmenopausal
      healthy women following oral administration of the bacteria in a yogurt base for
      1 month, as a first step in evaluating the potential probiotic role of LGG in the
      prevention of recurrent urinary tract infections. METHODS: One or two doses per
      day of yogurt containing 10(9) colony-forming units of LGG were administered
      orally to 42 postmenopausal healthy women for 1 month. Vaginal and rectal swabs
      were cultured at the beginning and end of the study. RESULTS: At the end of the
      study the vaginas of only four women (9.5%) were colonized with LGG, at a very
      low number of bacteria, despite the fact that the gastrointestinal tracts of 33
      women (78.6%) were colonized. There were no significant differences between one
      or two doses daily. CONCLUSIONS: LGG should not be considered as a probiotic
      agent in urinary infections since it does not attach well to the vaginal
      epithelium.

PMID- 14650099
TI  - Forgoing life-sustaining treatments: comparison of attitudes between Israeli and
      North American intensive care healthcare professionals.
AB  - BACKGROUND: Physicians' decisions regarding provision of life-sustaining
      treatment may be influenced considerably by non-medical variables. OBJECTIVES: To
      examine physicians' attitudes towards end-of-life decisions in Israel, comparing
      them to those found in the United States. METHODS: A survey was conducted among
      members of the Israel Society of Critical Care Medicine using a questionnaire
      analogous to that used in a similar study in the USA. RESULTS: Forty-three
      physicians (45%) responded, the majority of whom hold responsibility for
      withholding or withdrawing life-sustaining treatments. Preservation of life was
      considered the most important factor by 31 responders (72%). The quality of life
      as viewed by the patient was generally considered less important than the quality
      of life as viewed by the physician. Twenty-one responders (49%) considered
      withholding treatment more acceptable than withdrawing it. The main factors for
      decisions to withhold or withdraw therapy were a very low probability of survival
      of hospitalization, an irreversible acute disorder, and prior existence of
      chronic disorders. An almost similar percent of physicians (93% for Israel and
      94% for the U.S.) apply Do Not Resuscitate orders in their intensive care units,
      but much less (28% vs. 95%) actually discuss these orders with the families of
      their patients. CONCLUSIONS: Critical care physicians in Israel place similar
      emphasis on the value of life as their U.S. counterparts and assign DNR orders
      with an incidence equaling that of the U.S. They differ from their U.S.
      counterparts in that they confer less significance to the will of the patient,
      and do not consult as much with families of patients regarding DNR orders.

PMID- 14650100
TI  - Quick parathormone assay in the surgical management of hyperparathyroidism.
AB  - BACKGROUND: Among the various new technologies in the field of parathyroid
      surgery is intraoperative quick parathormone measurements. OBJECTIVES: To
      evaluate the contribution of QPTH measurements during parathyroidectomy to the
      achievement of higher success rates. METHODS: QPTH assay using Immulite Turbo
      Intact PTH was measured in 32 patients undergoing parathyroidectomy: 30 for
      primary and 2 for secondary hyperparathyroidism. QPTH levels were measured at
      time 0 minutes (before incision) and at 10, 20, and 30 minutes after excision of
      the hyperfunctioning gland. Only a drop of 60% or more from the 0' level was
      considered to be a positive result. RESULTS: The mean QPTH level at time 0' for
      PHPT patients was 38.12 +/- 25.15 pmol/L (range 9.1-118 pmol/L). At 10 minutes
      post-excision of the hyperfunctioning gland (or glands), QPTH dropped by a mean
      of 73.80% to 9.89 +/- 18.78 pmol/L. CONCLUSIONS: Intraoperative QPTH level
      measurement is helpful in parathyroid surgery. A drop of 60% or more from 0'
      level indicates a successful procedure, and further exploration should be
      avoided.

PMID- 14650101
TI  - The effect of montelukast on bronchial provocation tests and exhaled nitric oxide
      levels in asthmatic patients.
AB  - BACKGROUND: Leukotriene antagonist therapy in asthmatic patients alleviates
      symptoms and improves exercise tolerance, however the effect of these drugs on
      bronchial provocation tests and exhaled nitric oxide levels are less clearly
      established. OBJECTIVE: To determine the effect of montelukast treatment on
      airway hyperresponsiveness to exercise, methacholine and adenosine-5'
      monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics.
      METHODS: Following a 2 week run-in period, 20 mild to moderate asthmatics were
      enrolled in an open label 6 week trial of oral montelukast-sodium therapy.
      Bronchial hyperreactivity (exercise, methacholine and adenosine-5'-monophosphate
      challenges) and exhaled nitric oxide levels were measured before and after the 6
      week period. RESULTS: Montelukast treatment resulted in a significant improvement
      in exercise tolerance: median delta FEV1 20.0% (range 0-50) prior to treatment
      vs. 15.0% (range 0-50) post-treatment (P = 0.029). A significant difference was
      also observed for exhaled NO following therapy: median NO 16.0 ppb (range 7-41)
      vs. 13.0 (range 4.8-26) (P = 0.016). No change was seen in baseline lung function
      tests (FEV1, MEF50) or in the bronchial responsiveness (PC20) for methacholine
      and adenosine-5'-monophosphate. CONCLUSIONS: This study demonstrates that the
      leukotriene antagonist montelukast-sodium reduces bronchial hyperreactivity in
      response to exercise and reduces exhaled nitric oxide levels but has little
      effect on bronchial responsiveness to methacholine and adenosine challenges.

PMID- 14650102
TI  - The "DRIL" procedure--a neglected way to treat the "steal" syndrome of the
      hemodialysed patient.
AB  - BACKGROUND: The ischemic "steal" syndrome complicates angio-access in a growing
      number of hemodialysed patients. Until now, operative attempts (fistula ligation
      or banding) to treat this problem have met with only limited success. OBJECTIVE:
      To assess the results of DRIL (distal revascularization-interval ligation)
      procedure in treating the "steal" syndrome. METHODS: A retrospective review (1996
      2002) was conducted of all 11 patients who underwent the DRIL procedure in two
      tertiary care hemodialysis units. RESULTS: Two patients were excluded because of
      inadequate medical documentation. All of the nine patients remaining suffered
      from overt atherosclerotic disease, six had diabetic nephropathy and four were
      smokers. The arteriovenous access, which led to the "steal" syndrome, was
      proximally located in all (antecubital in 8, thigh area in 1). "Steal" symptoms
      included hand pain, paraesthesia, neurologic deficits and gangrenous ulcers. DRIL
      was technically successful in all patients. There were no perioperative deaths.
      Immediate and complete relief of pain was achieved in eight of the nine patients.
      One patient with gangrene later required a transmetacarpal amputation. No patient
      required hand amputation. During follow-up (range 1-26 months) hemodialysis was
      continued uninterruptedly using the problematic AVA in all patients. Thrombosis
      occurred in the AVA in only two patients after the DRIL procedure at 9 and 24
      months postoperatively, respectively. Three patient deaths were unrelated to the
      DRIL. CONCLUSIONS: In selected patients the DRIL procedure is a safe and
      effective way to treat the "steal" syndrome. AVA patency is not compromised by
      this operation. Preoperative angiography, before and after manual compression of
      the AVA, is crucial for the proper selection of patients who will benefit most
      from the DRIL procedure.

PMID- 14650103
TI  - Triage disposition of patients with acute myocardial infarction--ACSIS 2000.
AB  - BACKGROUND: In the emergency department the physician is often confronted with
      the decision of where to hospitalize a patient presenting with chest pain and a
      possible acute myocardial infarction--in the cardiac care unit or in the internal
      medicine ward. OBJECTIVE: To characterize the clinical factors involved in the
      triage disposition of patients hospitalized with AMI in Israel to either CCUs or
      IMWs and to determine to what extent the perceived probability of ischemia
      influenced the disposition decision. METHODS: During a 2 month nationwide
      prospective survey in the 26 CCUs and 82 of the 94 IMWs in Israel, we reviewed
      the charts of 1,648 patients with a discharge diagnosis of AMI. The probability
      of ischemia at admission was determined retrospectively by the Acute Coronary
      Ischemia Time-Insensitive Predictive Instrument. Co-morbidity was coded using the
      Index of Coexistent Diseases. RESULTS: The ACI-TIPI score for patients admitted
      to CCUs or to IMWs was 76.2% and 57.7% respectively (P < 0.001). Multivariate
      analysis showed that young patients with a high probability of ischemia and low
      co-morbidity or functional impairment were more likely to be hospitalized in CCUs
      than in IMWs. CONCLUSION: In Israel, the factors that strongly influence the
      initial triage disposition of AMI patients to CCUs or IMWs are age, perceived
      probability of ischemia, status of co-morbid conditions and functional
      impairment.

PMID- 14650104
TI  - Further evidence of interrelation between homocysteine and hypertension in stroke
      patients: a cross-sectional study.
AB  - BACKGROUND: A high total plasma homocysteine level is an independent risk factor
      for cardiovascular and cerebrovascular disease, but the evidence connecting
      plasma tHcy level with hypertension is inconsistent. OBJECTIVE: To determine the
      association between plasma tHcy level and some common risk factors for
      cerebrovascular disease (recurrent stroke, diabetes mellitus, hypertension,
      ischemic heart disease and hyperlipidemia) in patients presenting with primary or
      recurrent acute ischemic strokes. METHODS: This retrospective cross-sectional
      chart analysis was conducted in a university-affiliated referral hospital. During
      an 18 month period we identified 113 acute ischemic stroke patients (mean age
      71.2), 25 of whom had a recurrent stroke. Plasma tHcy level, obtained 2-10 days
      after stroke onset, was determined by the high performance liquid chromatography
      method with fluorescence detection. A multivariate logistic regression model was
      used to determine the independent relationship between each potential risk factor
      and tHcy level above or below the 75th percentile. RESULTS: Hypertension was more
      frequent among patients with plasma tHcy level above than below the 75th
      percentile (51.7% vs. 80.8%, respectively, P = 0.012). After adjusting for
      demographic and clinical variables, the odds ratio for recurrent stroke and
      hypertension, with tHcy above or below the 75th percentile, was 3.4 (95%
      confidence interval 1.01-10.4, P = 0.037) and 4.02 (95% CI 1.2-13.9, P = 0.028),
      respectively. CONCLUSIONS: A high plasma tHcy level is associated with history of
      hypertension and recurrent stroke among patients presenting with acute ischemic
      stroke. These results were independent of other risk factors such as atrial
      fibrillation, diabetes and hyperlipidemia. Hypertensive stroke patients with
      hyperhomocysteinemia should be identified as high risk patients as compared to
      non-hypertensive stroke patients, and more vigorous measures for secondary
      prevention may be warranted.

PMID- 14650105
TI  - Coronary intervention in thrombus-rich lesions: beyond stents and glycoprotein
      IIb/IIIa inhibitors.
AB  - Despite widespread use of stents and GP IIb/IIIa antagonists, complications
      following percutaneous treatment of thrombus-rich lesions continue to plague
      patients with ACS. In these patients the angiographically evident coronary
      thrombosis may represent a high degree of thrombus burden, which leads to a
      higher level of microembolization and its clinical sequelae. New catheter-based
      thrombus burden reduction systems and distal protection devices show promise for
      improving the prognosis of these high risk patients by decreasing distal
      microembolization, and thereby preventing myonecrosis. Careful procedural timing
      and patient selection are also likely to improve outcomes and resource
      utilization in the management of ACS patients.

PMID- 14650106
TI  - Cardiovascular disease in type 2 diabetics: epidemiology, risk factors and
      therapeutic modalities.
AB  - Macrovascular complications associated with chronic hyperglycemia in type 2
      diabetes mellitus is a major global health problem that is currently on the rise.
      Accelerated cardiovascular and cerebrovascular atherosclerosis is the major cause
      of mortality in patients with type 2 diabetes. Many of the risk factors for
      cardiovascular disease are operative or even exacerbated in diabetic patients,
      including hypercholesterolemia, hypertriglyceridemia, hypertension, central
      obesity, and smoking. Other diabetes-specific factors, such as increased levels
      of plasminogen activator 1 and fibrinogen, chronic inflammation, genetic
      susceptibility, and accelerated glycosylation end-products-mediated vascular
      damage, are thought to play a role in the development of CVD among patients with
      type 2 diabetes. Further studies will hopefully elucidate the clinical relevance
      of such factors. In addition, recent studies indicate that hyperglycemia is an
      important and independent risk factor for CVD. Increased risk of CVD is directly
      related to elevated 1 and 2 hour post-prandial blood glucose averages, as well as
      to fasting hyperglycemia. Thus, specific treatment regimens designed to reduce
      the development rate of cardiovascular complications in patients with type 2
      diabetes must consider the impact of risk factors and their control, as well as
      the need for optimal metabolic and glycemic control.

PMID- 14650107
TI  - The head-up tilt test in the diagnosis and management of chronic fatigue
      syndrome.

PMID- 14650108
TI  - Intelligent nutrition: health-promoting mechanisms of probiotics.

PMID- 14650109
TI  - Infection and anti-tumor necrosis factor-alpha therapy.

PMID- 14650110
TI  - Infliximab for the treatment of extensive plaque psoriasis--regulation, cost and
      reimbursement.

PMID- 14650111
TI  - The changing face of Lemierre's syndrome.

PMID- 14650112
TI  - Genetic polymorphisms of the beta-2 adrenergic receptor in Israelis with severe
      asthma compared to non-asthmatic Israelis.
AB  - BACKGROUND: It has been argued that arginine replacement in locus 16 (Arg16) of
      beta 2 adrenergic receptor with glycin (Gly16) increases asthma severity, while
      glutamin replacement in locus 27 (Gln27) with glutamic acid (Glu27) decreases it.
      In addition, ethnic dependency of these polymorphisms has been described, but few
      studies investigated its relation to asthma severity in a non-anglosaxic
      population. OBJECTIVES: To investigate non-anglosaxic ethnic influences on beta
      2AR polymorphisms and its correlations to asthma severity. METHODS: Sixty-six
      Israeli Jewish and Arab asthmatics who had near-fatal asthma and/or severe
      nocturnal asthma and/or steroid-dependency were investigated for genetic
      polymorphisms of beta 2AR and compared to matched controls. The Jewish patients
      included both Ashkenazi (of European origin) and non-Ashkenazi (originating from
      the Middle East or North Africa). The results were compared with those of
      ethnically matched 113 non-asthmatic Israelis and non-asthmatic Anglo-Saxons
      described in the literature. RESULTS: We found no significant genetic differences
      between the asthmatics and their controls or between the various ethnic groups of
      our population. However, the prevalence of Glu27 was significantly lower in non
      asthmatic Israelis compared to non-asthmatic Anglo-Saxons. CONCLUSIONS: The
      genetic distribution of beta 2AR polymorphisms in severe Israeli asthmatics is
      not different from that of non-asthmatic Israelis and therefore its clinical
      impact on asthma is probably minimal.

PMID- 14650113
TI  - Orbital myositis in a patient with primary biliary cirrhosis: successful
      treatment with methotrexate and corticosteroids.

PMID- 14650114
TI  - Infliximab-induced remission of extensive plaque psoriasis.

PMID- 14650115
TI  - Listeria monocytogenes sepsis in patients treated with anti-tumor necrosis factor
      alpha.

PMID- 14650116
TI  - Lemierre's syndrome: a rare clinical condition diagnosed, exceptionally, by
      imaging.

PMID- 14650117
TI  - Complete response of brain metastases originating in breast cancer to
      capecitabine therapy.

PMID- 14650118
TI  - CT diagnosis of an acute epiploic appendagitis in a redundant sigmoid colon
      clinically suspected as acute appendicitis.

PMID- 14650119
TI  - Legionella-Rickettsia co-infection or serologic cross-reactions?

PMID- 14650120
TI  - Do patients recall and understand communicated information upon discharge from
      the emergency department?

PMID- 14650121
TI  - Bone crises in Gaucher disease.

PMID- 14650122
TI  - Influenza vaccination and reduced risk of myocardial infarction.

PMID- 14650123
TI  - [Quality of life parameters in assessment of efficacy of sanatorium treatment in
      elderly patients with hypertension].
AB  - Questionnaires specially developed for estimation of quality of life in
      hypertensive elderly patients were used in 70 patients taking sanatorium
      treatment at Urkutsk health resort Angara. It is shown that a course of chloride
      sodium mineral baths normalizes quality of life of elderly patients with
      hypertension.

PMID- 14650124
TI  - [Extracorporeal autohemomagnetotherapy in treatment of patients with rheumatoid
      arthritis].

PMID- 14650125
TI  - [Immunological phenotype of skin lymphoid cells in patients with psoriatic
      arthritis during rehabilitation].

PMID- 14650126
TI  - [Modulated kinesitherapy in rehabilitation of patients with cardiovascular
      diseases].
AB  - Modulated kinesitherapy (MK) is a new method based on synchronization of
      vegetative and motor components in walking at a pace corresponding to actual
      heart rate which is maintained during the procedure with cardiotrainer Marafon.
      MK produced the following therapeutic effects: optimization of cardiovascular
      functions (weakening of postload on the heart with lowering of arterial pressure;
      improvement of coronary blood flow, stabilization of the heart rate and cardiac
      pump function); marked antiarrhythmic effect, normalization of autonomic nervous
      system tonicity, neurohumoral and psychoemotional state. MK is indicated in
      ischemic heart disease, essential hypertension, cardiac arrhythmia,
      vegetovascular asthenia.

PMID- 14650127
TI  - [Biocontrolled aeroionotherapy--a new method of treatment in patients with
      bronchial asthma].

PMID- 14650128
TI  - [Evaluation of the efficacy of physical exercises in scoliotic disease].
AB  - Scoliotic disease manifests in the course of skeletal growth and requires long
      term specialized treatment. Special literature does not present sound criteria of
      efficacy of exercise treatment of scoliosis in children and adolescents. The
      proposed comprehensive score assessment of body function of children and
      adolescents with scoliosis, objectively characterizes its dynamics, response to
      therapeutic procedure including exercise therapy.

PMID- 14650129
TI  - [SMC-electrophoresis of peat mud in the treatment of patients with duodenal ulcer
      in outpatient care unit].
AB  - To study collagen metabolism in reparative regeneration of duodenal ulcer in
      response to peat mud electrophoresis of Uva sanatorium using sinusoidal modulated
      currents (SMC) as monotherapy in a day hospital, 82 duodenal ulcer patients in
      exacerbation or attenuation were examined. They received SMC-electrophoresis of
      peat mud diluted by sulfate sodium-calcium mineral water Uvinskaya of moderate
      mineralization. The dynamics of clinico-endoscopic and morphological picture of
      the disease was controlled with fibrogastroduodenoscopy with target biopsy of the
      periulcer zone and antral stomach, investigation of secretory and acid-producing
      function of the stomach, hormone profile and collagen metabolism. Positive
      changes were found attributed to favourable shifts in the hormone status and
      normalization of collagen metabolism in duodenal mucosa.

PMID- 14650130
TI  - [Effect of impulse infrared laser radiation on bioenergetic metabolism in gastric
      mucosa in patients with gastroduodenal ulcer].
AB  - Gastric mucosa and blood plasm were studied in 82 patients with gastroduodenal
      ulcer for content of adenylic nucleotides (AMP, ADP and ATP), histamine, amino
      acids. It was found that the above nucleotides occurred in the examinees in
      subnormal quantities. The necessary substrates, aspartate in particular, were
      deficient. This may lead to impairment of biosynthetic processes, to imbalance of
      defense factors. Photon therapy of gastroduodenal ulcer corrects bioenergetic
      metabolism in gastric mucosa thus producing a marked therapeutic effect.

PMID- 14650131
TI  - [Laser therapy and cryomassage in rehabilitation of patients with facial nerve
      neuropathy].
AB  - Cryomassage and its combination with low-intensity infra-red laser radiation have
      been introduced as a novel treatment of facial nerve neuropathy (FNN) in 32
      patients. Electrophysiological investigations (facial thermography, classical
      electrodiagnosis, electromyography of the mimic muscles) and clinical data
      including those of long-term follow-up show that neither cryomassage nor infra
      red laser radiation studied promote transformation of facial tissues in FNN
      patients. Use of the above factors is effective in a preclinical stage of forming
      contracture of the mimic muscles. Special techniques of application of local
      hypothermia and laser radiation can be used in multimodality treatment of both
      the established contracture and sluggish paresis of the facial muscles.

PMID- 14650132
TI  - [Effect of oxygen baths and massage on hemodynamics in patients with
      neurocirculatory dystonia].
AB  - 56 patients with neurocirculatory asthenia (NCA) of a hypertensive and cardial
      type aged 30 to 55 years took general oxygen baths and collar zone massage, no
      drugs were used. The baths and the massage improved the disease course in 92.6%
      patients: improved hemodynamics, relieved high vascular resistance, lowered high
      diastolic blood pressure, decreased heart rate in tachycardia. More effective was
      the treatment in hypertensive NCA.

PMID- 14650133
TI  - [Application of sinusoidal modulated currents and radon therapy in patients with
      uroliths in upper urinary tracts].
AB  - The paper describes the method of elimination of the upper urinary tract uroliths
      using a combination of the following modalities: sinusoidal modulated currents,
      drinking of artificial radon water, radon water baths and no-spa medication.
      Evacuation of the concrements or their fragments from the upper urinary tracts
      reached 80%.

PMID- 14650134
TI  - [Physical factors in therapy of patients with climacteric syndrome in
      postmenopause].

PMID- 14650135
TI  - [Effect of peloid therapy on morphofunctional changes of ovaries and oviducts
      caused by suturing (experimental study)].
AB  - A course of ultraphonophoresis of the extract of high-polar lipids of sulfide mud
      attenuated inflammation of uterine appendages in rats caused by catgut suturing
      of the ovaries and oviducts. On postoperative day 75-120 peloid therapy resulted
      in degradation of the suture material and its replacement with connective tissue.
      The peloid limited postoperative intensification of follicular atresia, raised
      content of growing follicles and yellow bodies in the ovaries.

PMID- 14650136
TI  - [Economic evaluation of efficiency of medico-rehabilitation institutions].

PMID- 14650137
TI  - [Indicative role of enterococci in sanitary evaluation of mineral waters].

PMID- 14650138
TI  - [Lipid metabolism in patients with the late sequelae of combined craniocervical
      trauma and its correction at the health resort stage].

PMID- 14650139
TI  - [Pathogenetic substantiation of sinusoidal modulated currents phoresis of drugs
      in children with various forms of alopecia areata].

PMID- 14650140
TI  - [Lipid composition of therapeutic muds].

PMID- 14650141
TI  - [Rehabilitation treatment of somato-neurological disorders].

PMID- 14650142
TI  - [Laser therapy in gastroenterology].

PMID- 14650143
TI  - [Analysis on the SARS-CoV genome of PUMC01 isolate].
AB  - OBJECTIVE: To perform variation and phylogenetics analysis on the SARS-CoV genome
      sequence (PUMC01) isolated in the Peking Union Medical College Hospital. METHODS:
      The cDNA library of SARS-CoV (PUMC01 isolate) was constructed by means of random
      priming strategy. Random selected plasmid was sequenced and the genome sequence
      of SARS-CoV-PUMC01 was assembled by conventional methods (The Genebank Accession
      No. of SARS-CoV-PUMC01 is AY350750). The variation and phylogenetics analysis
      were performed by comparing the PUMC01 sequence with other SARS-CoV isolates.
      RESULTS: Ten variation sites were found by comparing PUMC01 isolate with Tor2 and
      Urbani isolates. In phylogenetic analysis of 18 SARS-CoV isolates, two classes
      were observed and there is different differential time between these two classes
      and the different isolates in each class. CONCLUSIONS: The evidence of
      phylogenetic analysis of different SARS-CoV isolates from different region is
      instructive for understanding the clinical relations between the different
      isolates and the transmission chain of SARS-CoV.

PMID- 14650144
TI  - [cDNAs cloning of SARS-CoV PUMC2 viral genome].
AB  - OBJECTIVE: To get the cDNA clones which cover the whole genome of SARS-CoV PUMC2
      strain. METHODS: Using the SARS-CoV PUMC2 strain genomic RNA as the template, the
      cDNA fragments were amplified by RT-PCR, the PCR products were further purified
      and ligated into the pGEM-T vector, and all the clones obtained were sequenced.
      RESULTS: The cDNA clones which cover the whole genome of SARS-CoV PUMC2 strain
      were obtained. CONCLUSIONS: These cDNAs can be provided for the function study of
      SARS-CoV proteins and the construction of full-length infectious cDNA clone of
      SARS-CoV.

PMID- 14650145
TI  - [Cloning, expression and purification of SARS coronavirus PUMC2 strain
      nucleocapsid protein].
AB  - OBJECTIVE: To clone, express and purify nucleocapsid protein from SARS
      coronavirus PUMC2 strain. METHODS: According to the published SARS coronavirus
      genome sequences, the full length cDNA of N protein from SARS coronavirus PUMC2
      strain was cloned by RT-PCR and the cDNA was cloned into the pET32a expression
      vector. The recombinant N protein was expressed in E. coli BL21 (DE3), and
      purified by Ni(2+)-NTA. RESULTS: Prokaryoticly expressed and purified N protein
      of SARS coronavirus PUMC2 strain was obtained. CONCLUSIONS: The SARS coronavirus
      recombinant N protein obtained by genetic engineering methods can be used for
      further functional study of SARS coronavirus N protein.

PMID- 14650146
TI  - [Immunohistochemical investigation of lungs with severe acute respiratory
      syndrome].
AB  - OBJECTIVE: To investigate the roles of different cells in the pulmonary lesions
      in the severe acute respiratory syndrome (SARS) patients. METHODS: The monoclonal
      antibodies of CD8, CD20, CD34, LCA, CD56, CD68, and AE1/AE3 are used to
      demonstrate the different cells in the lung specimens of SARS patients in order
      to study the patterns of cell responses in this new disease. Meanwhile the HE
      stained slides were also carefully studied to compare with the results of
      immunohistochemical staining. RESULTS: The number of capillaries increased and
      the capillaries clearly outlined the contour of alveolar wall from beginning to
      early stage of organization, the number of lymphocytes decreased sharply while
      the number of macrophage remarkably increased, together with proliferation of
      type II pneumocytes. The numbers of blood vessels decreased in the fibrotic and
      consolidated lung tissue, and the vessel cavities enlarged, losing the normal
      contour of alveolar septa. CONCLUSIONS: The lesions in the lung from SARS
      patients are consisted of the tissue reaction to the inflammatory injury,
      including extensive exudation, capillary proliferation, fibrosis, and obvious
      infiltration of macrophages which may play a key role in the pathogenesis of
      pulmonary lesions of SARS.

PMID- 14650147
TI  - [Thoracic high resolution CT findings of 100 SARS patients in convalescent
      period].
AB  - OBJECTIVE: To study thoracic high resolution CT findings of severe acute
      respiratory syndrome (SARS) patients in convalescent period and the relationship
      between the features with laboratory and pulmonary function results. METHODS: All
      the 100 SARS patients who had been discharged from hospital for about 2 months
      underwent thoracic high resolution CT examinations. Among them, 65 also had
      laboratory results and 91 underwent examinations of pulmonary function. RESULTS:
      Forty-nine SARS patients (49.0%, 49/100) in convalescent period still had
      abnormal findings in CT examination. And ground-glass opacification (95.9%,
      47/49) and reticular opacification (59.2%, 29/49) were common. There was no
      significant difference in the level of lymphocytes and CD4 cells among groups
      divided according to severity of CT findings (P > 0.01). Diffusing capacity for
      carbon monoxide (DLco%) of level 2 and 3 were statistically lower than that of
      level 0 (P < 0.01). CONCLUSIONS: The features of CT findings of SARS patients in
      convalescent period are not the same as those of patients in period of apparent
      manifestation. The high resolution CT can reflect pulmonary diffusing function to
      some degree.

PMID- 14650148
TI  - [Assessment of health-related quality of life in cured SARS patients].
AB  - OBJECTIVE: To assess the quality of life in cured patients with severe acute
      respiratory syndrome (SARS). METHODS: One hundred and nineteen SARS outpatients,
      including 64 men and 55 women, with mean age (34.1 +/- 11.4) years and average
      days of discharge from hospital (28.0 +/- 12.8) days, were assessed by the St
      George's respiratory questionnaire (SGRQ), and 72 patients with spirometry test.
      RESULTS: The patients had a moderately degree physiological impairment and
      increased SGRQ score. Scores of all four part of SGRQ correlated significantly
      with diffuse capacity of the lung for carbon monoxide/pre (DLco%). The
      correlation coefficients between the activation, impaction, total score, and
      diffuse capacity of the lung for carbon monoxide/alveolar ventilation/pre
      (DLco/Va%) were resembled (r = 0.47-0.54, P < 0.01). There was a significant
      relationship between the score of SGRQ and patients age, and gender. The time
      leaving hospital only had a significant relationship with the symptom score of
      SGRQ. CONCLUSIONS: SGRQ is a sensitive tool for assessing quality of life in
      cured SARS patients. The cured SARS patients' quality of life decrease
      moderately.

PMID- 14650149
TI  - [Isolation and identification of SARS-coronavirus in nasal and throat swabs
      collected from clinically diagnosed SARS patients].
AB  - OBJECTIVE: To isolate and identify SARS-coronavirus in nasal and throat swabs
      collected from clinically diagnosed severe acute respiratory syndrome (SARS)
      patients. METHODS: Nasal and throat swab specimens were inoculated onto well of
      24-well plate containing confluent monolayers of Vero and MRC-5 cells. Isolates
      were identified with serology, electron microscopy and genome sequence. RESULTS:
      One hundred and fifty-eight nasal and throat swabs specimens from 79 SARS
      patients in Peking Union Medical College Hospital between April and May, 2003
      were cultured for SARS-coronavirus. Cytopathic effect (CPE) was found in three
      nasal swab specimens inoculated in Vero cells. Acute and convalescent phase serum
      specimens collected from SARS patients were found with seroconversions and/or a
      fourfold or greater rises in indirect fluorescence antibodies (IgG and IgM)
      titers when the 3 isolates (infected Vero cells) were used as antigen.
      Coronavirus was observed in the culture supernatant by negative-stain electron
      microscopy. Genome sequence confirmed the isolates were SARS-coronavirus.
      CONCLUSIONS: The 3 isolates from nasal and throat swabs samples collected from 79
      clinically diagnosed SARS patients were SARS coronavirus.

PMID- 14650150
TI  - [Dynamics of T lymphocyte subsets in SARS patients].
AB  - OBJECTIVE: To study dynamics of T lymphocyte subsets in severe acute respiratory
      syndrome (SARS). METHODS: Sequential anti-coagulated blood samples were collected
      from 46 cases of SARS patients during the 1st week, the 2nd week, the 3rd-5th
      week and the 8th-12th week after the infection. T lymphocyte subsets including
      CD3+CD4+ cells, CD3+CD8+ cells, naive CD4+ cells (CD4+CD45RA+CD62L+) and
      activated CD8+ cells (CD8+CD38+) were detected by 3-color flow cytometry. Fifty
      six normal healthy blood donors were also detected as normal controls. RESULTS:
      Compared with the results of normal controls, both of the percentages of CD4+
      cells and CD8+ cells of SARS patients were in normal levels during the 1st week,
      but the cell counts decreased significantly to (306 +/- 140)/mm3 and (270 +/-
      143)/mm3, respectively. The cell count of naive CD4+ subset also remarkably
      decreased to (96 +/- 49)/mm3, and the percentage of CD8+CD38+ subset was higher
      than that of normal controls [(59.3 +/- 12.6)% vs (44.9 +/- 12.5)%]. During the
      3rd-5th week, the CD8+ cell count and the percentage of CD8+CD38+ subset reached
      normal values, which were (581 +/- 356)/mm3 and (40.1 +/- 17.6)%, respectively.
      During the 8th-12th week, the cell counts of CD4+ cell [(578 +/- 193)/mm3] and
      naive CD4+ subset [(176 +/- 64)/mm3] were still less than those of normal
      controls, while compared with those of the 1st week, the increments were
      remarkable. CONCLUSIONS: T lymphocytes of SARS patients decreased dramatically
      but could be obviously resumed in a short time. It will take more than 8-12 weeks
      for CD4+ cell and naive CD4+ subset to reach to normal levels.

PMID- 14650151
TI  - [Assessment of pulmonary function in SARS patients during the convalescent
      period].
AB  - OBJECTIVE: To investigate the pulmonary function in severe acute respiratory
      syndrome (SARS) patients during the convalescent period. METHODS: Followup 89
      outpatients of SARS. The follow-up study included interview, physical
      examination, and pulmonary function test. RESULTS: The interval between hospital
      discharge and functional assessment was 1.75 +/- 0.53 months (0.5-3.4 months).
      Mild to moderate abnormalities in pulmonary function were found in 48 patients
      (53.9%). Diffusion capacity for carbon monoxide (DLco) was impaired in 38
      patients (42.7%); in 7 patients (7.9%), lung function was restrictive defect
      combined DLco impairment; Other patterns of impairment were revealed in 3
      patient. Dyspnea during acute phase and CT during the convalescent period were
      found to have significant influences on DLco and total lung capacity (TLC).
      CONCLUSIONS: Diffusing capacity impairment as well as restrictive defect persist
      in convalescence SARS.

PMID- 14650152
TI  - [An outbreak of SARS in Dongcheng District, Beijing during March to June 2003].
AB  - OBJECTIVE: To describe epidemiological characteristics of an outbreak of severe
      acute respiratory syndrome (SRAS) in Dongcheng District, Beijing during March to
      June 2003. METHODS: Data of SARS cases notified from Dongcheng District Center
      for Disease Control and Prevention (CDC) and supplemented by other channels were
      collected. All data were input into dataset files by Microsoft Excel-2000
      software and analyzed with SPSS version 10.0 software. RESULTS: Totally, 572
      cases notified were collected during this period in Dongcheng District, Beijing,
      and 99 of them were excluded from SARS, because of diagnosis of common cold,
      pneumonia, measles, or rubella, etc. Actually, 473 SARS cases were analyzed.
      Attack rate of SARS in permanent residents of Dongcheng was 28.3 per 100,000.
      Forty-one of them died, with a case-fatality ratio of 8.7%. Outbreak of SARS in
      Dongcheng District started on March 14, with a peak during mid- and late April,
      and dropped from May 5, 2003. Persons were all susceptible to SARS, with the
      highest proportion at ages of 20-50 years, which accounted for 68.7% of the total
      cases. Average age of the patients at their onset was 40.7 years. No gender
      difference in SARS cases was found. Number of SARS cases in health care workers
      (HCWs) accounted for 18.0% and that in the retired persons accounted for 15.4% of
      the total cases. Cases occurred in all 10 sub-districts of Dongcheng. Totally,
      230 of the 572 notified cases (40.2%) hospitalized at local hospitals under the
      jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in
      health care workers of local hospitals, accounting for 4.5% of the total number
      of health care workers working at the wards caring for SARS patients or at fever
      clinics. There were 34.7% of SARS cases without any contact histories before
      their onset. Familial aggregation phenomena were observed in 41.8% of the cases
      and 18.1% of households. And, 7.4% (attack rate) in those exposed to SARS cases
      suffered the illness during the periods of quarantine. CONCLUSIONS: SARS appeared
      outbreak in Dongcheng District, Beijing during March to June 2003. People were
      all susceptible to SARS, which mainly threatened the young adults and the middle
      aged, as well as health care workers and the retired workers. Main mode of
      transmission was exposure to SARS patients in a near distance at hospitals or
      families. Prevention and control of SARS should be focused on early isolation of
      patients and quarantine for the contacts. Current available measures to prevent
      and control SARS proved effective.

PMID- 14650153
TI  - [Reliability of detecting SARS-CoV antibody for diagnosis of SARS].
AB  - OBJECTIVE: To discuss the reliability of SARS-CoV antibody detection for SARS
      diagnosis. METHODS: Using SARS-CoV ELISA kit to detect relevant antibody in fresh
      serum of healthy, fever, probable, and suspect cases. RESULTS: The positive rate
      is 0%, 40%, and 95% respectively in healthy, probable, and suspect cases.
      CONCLUSIONS: It is reliable to detect SARS-CoV antibody in late suspect patients,
      but there will be high false-positive result in ordinary fever cases.

PMID- 14650154
TI  - [Change of T lymphocyte and its activated subsets in SARS patients].
AB  - OBJECTIVE: To study abnormal changes of T lymphocyte and its activated subsets in
      severe acute respiratory syndrome (SARS) patients. METHODS: Flow cytometer with
      multi-color flouroscence and hematology analyzer were used to detect the
      expression of T lymphocyte and its activated a subsets in 240 SARS patients
      including 50 cases of critical type and 190 cases of common type. RESULTS:
      Statistical analysis by means of SAS software showed that there was significant
      decrease in absolute counts (AC) of T lymphocyte and its subsets in SARS patients
      when compared with normal people, while percentages (PC) of CD3+CD25+ and CD3+
      HLA-DR+ subsets were increased markedly. Compared with common type, there was
      significant decrease in absolute counts of critical type of T lymphocyte, CD4+,
      CD25+CD3+, CD28+CD4+, and CD95+CD4+subsets. The ACs of T lymphocytes including
      CD4 and CD8 subsets in different phases were as below: III > II > I. The ACs of
      subsets involved in activation such as CD3+ HLA-DR+/lym, CD3+CD25+/lym,
      CD28+CD4+/CD4, CD28+CD8+/CD8, and CD38+CD4+/CD4 all were highest in group III. In
      addition, the AC and PC of CD95+CD4+/CD4 and CD95+CD8/CD8 subset in group III
      were highest while group I was lowest. CONCLUSIONS: With depressing cellular
      immunity, the activation of T lymphocytes were suppressed obviously in SARS
      patients, especially for critical patients.

PMID- 14650155
TI  - [Clinical diagnosis, treatment and prognosis of elderly SARS patients].
AB  - OBJECTIVE: To discuss the clinical manifestations, therapeutic strategy and
      prognosis of patients with severe acute respiratory syndrome (SARS) older than 60
      years. METHODS: Elderly patients diagnosed as SARS in Peking Union Medical
      College Hospital were compared with younger patients. RESULTS: Twenty-four
      elderly patients and 53 younger patients were analysed. Elderly patients had more
      coexisting conditions, such as hypertension, diabetes, coronary heart disease,
      and renal disease than control group (P < 0.05). Rate of respiratory failure in
      elderly patients was higher than that in control group (P < 0.05). Elderly
      patients had more respiratory symptoms, such as cough, sputum, and shortness of
      breath (P < 0.05). Rate of lymphocytopenia and thrombocytopenia in elderly
      patients was higher than that in control group. All patients were given ribavirin
      and antibiotics. More patients in elderly group were given 3rd generation
      cephalosporin and imipenem. Mortality rate in elderly group was higher than that
      in control group (33.3% vs 3.8%, P < 0.05). Univariate analysis showed that age,
      respiratory failure, and thrombocytopenia were risk factors of death, but
      logistic analysis did not find any independent risk factor. CONCLUSIONS: Though
      the elderly patients have a lower morbidity of SARS, they have more coexisting
      conditions. The therapy of elderly patients is more difficult than that of
      control group, and the mortality in elderly patients is high.

PMID- 14650156
TI  - [Evaluation of tracheal intubation in critical SARS patients].
AB  - OBJECTIVE: To analyze tracheal intubation and respiratory treatment in the
      critical severe acute respiratory syndrome (SARS) patients. METHODS: Review and
      analyze tracheal intubation and respiratory treatment in critical SARS patients
      in intensive care unit (ICU). RESULTS: Three of thirteen patients had been
      intubated or received tracheotomy before they entered into ICU, the other
      patients received treatment of nasal cannula or oxygen mask. With the development
      of the disease, two patients had been intubated because of respiratory failure or
      tracheotomy. Tracheal intubation was twice made in two patients in order to
      replace tracheal tubes. CONCLUSIONS: The patient should be intubated or received
      tracheotomy if non-invasive respiratory support has no effect. Standard
      protection could protect medical staff from infection under tracheal intubation.

PMID- 14650157
TI  - [Effect of tetramethylpyrazine on learning, memory and cholinergic system in D
      galactose-lesioned mice].
AB  - OBJECTIVE: To explore the effect of tetramethylpyrazine on learning, memory, and
      cholinergic system in D-galactose-lesioned mice. METHODS: C57BL/6J mice were
      given subcutaneous injection of 2% D-galactose for 40 days (100 mg.kg-1.d-1).
      Normal saline, tetramethylpyrazine (TMP) and Huperzine A (HupA) were given
      respectively by intragastric administration in different study groups from the
      third week on. Learning and memory ability were tested by Morris water maze for 5
      days at the sixth week. Acetylcholinesterase (AchE) activity, the binding sites
      (Bmax) and the affinity (KD) of M-cholinergic receptor were determined. RESULTS:
      The learning and memory dysfunction, with lowered AchE activity and M-cholinergic
      receptor binding sites were found in the model group as compared with the normal
      control group. The tetramethylpyrazine, especially at the dose of 100 mg.kg-1.d
      1, could markedly attenuate cognitive dysfunction, while elevate the lowered AchE
      activity (P < 0.05) and M-cholinergic receptor binding sites (P < 0.005) in the
      cerebral cortex of mice treated with D-galactose. CONCLUSIONS: The
      tetramethylpyrazine can significantly improve central cholinergic system
      function, and thus enhance the learning and memory ability in D-galactose
      lesioned mice.

PMID- 14650158
TI  - [Cloning and expression of human single-chain Fv antibody against amyloid beta
      peptide involved in Alzheimer's disease].
AB  - OBJECTIVE: To screen out the specific antibody clones against amyloid beta
      peptide 40, and clone the antibody gene and express it in a bacterial system, so
      as to provide a solid basis for novel diagnostic and therapeutic methods for
      Alzheimer's Disease. METHODS: beta amyloid peptide 40 was bound on the solid
      surface of Nunc plates as antigen to screen the binding clones from a phage
      display human single-chain Fv antibody library. After five rounds of bio-panning,
      the host E. coli TG1 was infected with eluted filamentous phage from the last
      turn of selection. 55 well-separated colonies were picked randomly from the
      plates and the specific positive clones were identified by ELISA test. The single
      chain Fv antibody gene was sequenced and their amino acids sequence was deduced.
      The scFv antibody gene was sub-cloned into a protokayotic expression vector pGEX
      6P-1 and transformed into bacteria strain BL21 to express the glutathione-S
      transferase (GST) fusion single-chain antibody. RESULTS: ELISA test showed that
      33 of the 55 clones could bind amyloid beta peptide 40 and 10 of the 33 clones
      could be inhibited by amyloid beta peptide 40 itself to below 50% of its original
      binding activities. Five of the 10 clones could also be inhibited by amyloid beta
      peptide 1-16 to the same level, which meant that the binding epitope of the
      antibody from the 5 clones was between first to sixteenth amino acids at amino
      end of amyloid beta peptide 40. DNA sequencing data demonstrated that the gene of
      the single-chain antibody specifically against amyloid beta peptide 40 was
      consisted of 768 bp and the deduced amino acids sequence confirmed its typical
      antibody structure. The complement determinant regions and framework regions were
      discriminated empirically. After cloning the antibody gene into a protokayotic
      system, the GST fusion antibody was expressed as the expected size. CONCLUSIONS:
      After five rounds of bio-panning and subsequently serial ELISA testing, the
      specific antibody clones against amyloid beta peptide 40 were screened out
      successfully. The antibody gene DNA sequence and amino acids sequence were
      analyzed and confirmed. The fusion antibody was expressed as expected in the
      bacterial system.

PMID- 14650159
TI  - [Preliminary clinical application of 99Tcm-HYNIC-TOC imaging in somatostatin
      receptor-positive tumors].
AB  - OBJECTIVE: To evaluate the effect of 99Tcm-HYNIC-TOC imaging in localization of
      somatostatin receptor-positive tumors. METHODS: Forty-four patients were involved
      in this study, including 22 neuroendocrine tumors, 10 non-neuroendrocrine tumors
      and 12 benign diseases. All patients were confirmed by histopathologic diagnosis,
      and had clinical laboratory data, or 1-2 other imaging procedures. Regional,
      whole body and SPECT/CT (in positive cases) imagings were acquired at 1 and 4
      hours after an intravenous injection of 370 MBq 99Tcm-HYNIC-TOC. 99Tcm-HYNIC-TOC
      imaging was compared with 111In-petetreotide imaging in 4 cases, and with 131I
      MIBG imaging in 10 cases. 99Tcm-HYNIC-TOC imaging was performed before and after
      treatment in 1 non-Hodgkins lymphoma (NHL) patient. RESULTS: The positive
      imagings were observed in 19 of 32 cases. The sensitivity, specificity, and
      accuracy of 99Tcm-HYNIC-TOC imaging for somatostatin receptor-positive tumors are
      82.6%, 100%, and 87.5%, respectively. The distribution in vivo of 99Tcm-HYNIC-TOC
      is similar to that of 111In-petetreotide, and showed high physiological uptake in
      liver, spleen, and kidneys. 99Tcm-HYNIC-TOC imaging demonstrated intense tumor
      sites uptake at 1 hour after injection, and revealed the lesions first in 6
      patients among the imaging modalities, and more lesions that had not been
      revealed by 131I-MIBG imaging. Compared with imaging before treatment, 99Tcm
      HYNIC-TOC imaging confirmed the tumor regression after treatment in 1NHL.
      CONCLUSIONS: 99Tcm-HYNIC-TOC is promising for the diagnosis and localization of
      somatostatin receptor-positive tumors.

PMID- 14650160
TI  - [Mechanism of carbapenems resistance in Acinetobacter baumannii].
AB  - OBJECTIVE: To investigate the mechanism of carbapenems resistance in
      Acinetobacter baumannii. METHODS: WHONET-5 software was used to analyze the trend
      of carbapenem resistance in Acinetobacter baumannii collected from 1999 to 2001
      at Peking Union Medical College Hospital. Analytical isoelectric focusing was
      used to measure the pI of the beta-lactamase. Conjugation experiment was used to
      study the transfer of carbapenem resistance and plasmid DNA was extracted and
      purified with Qiagen Plasmid Mini Kit. The homology of the isolates was
      determined by pulsed field gel electrophoresis (PFGE). Integrase genes and blaIMP
      , blaVIM-, blaOXA- genes for resistant isolates were amplified and sequenced.
      RESULTS: Imipenem resistance in A. baumannii was ranged from 1.8%-8.5%, but only
      9 resistant isolates were viable. They were co-resistant to other carbapenems,
      ceftazidime, aztreonam, and gentamicin, and four isolates were resistant to
      ciprofloxacin. Impipenem resistance could not be transferred to susceptible
      strains. No plasmid was extracted. Each isolate produced TEM-1, AmpC, and two
      enzymes (pI 6.7, 6.0), which can not be inhibited by cloxacillin and clavulanic
      acid. Each isolate had class I intergase gene. Nine isolates were all negative
      for PCR of blaIMP- and blaVIM- genes, but positive for blaOXA-23 specific PCR.
      Sequencing found 100% homology with blaOXA-23. PFGE found 3 clones (A type: 5
      isolates; B type: 3 isolates; C type: 1 isolate). Control isolates (imipenem
      susceptible, but ceftazidime, ciprofloxacin, and gentamicin resistant) were also
      A clone. CONCLUSIONS: Production of OXA-23 carbapenemase in A. baumannii was one
      of the main mechanisms of carbapenems resistance at our hospital. It brings
      concern that imipenem-resistant clone has evoluted from nosocomial multiple
      resistant strains.

PMID- 14650161
TI  - [Cloning associated genes using microdissection-cDNA PCR-SSH in gastric
      dysplasia].
AB  - OBJECTIVE: To construct cDNA subtracted libraries from gastric dysplasia and
      further screen differentially expressed genes. METHODS: Relatively pure dysplasia
      and normal tissue were procured by manual microdissection, and amplified by cDNA
      PCR, which was used to carry on for suppression subtractive hybridization (SSH).
      Subtracted cDNA fragments were linked with vector, cloned, screened, sequenced,
      and made homologous search. Differentially expressed fragments were verified by
      dot hybridization. RESULTS: Two subtracted cDNA libraries were constructed. Among
      26 sequenced clones, 15 fragments corresponded to known genes, 3 fragments were
      known EST and 8 fragments were unknown EST (GenBank BQ164614-BQ164616, BQ291516
      BQ291520). Fifteen fragments were verified to be differentially expressed in
      gastric dysplasia. CONCLUSIONS: Subtracted cDNA libraries from gastric dysplasia
      are constructed using combination of microdissection-cDNA PCR and SSH setup in
      our laboratory. Some fragments have been screened and verified to help to search
      for novel associated genes with gastric carcinogenesis.

PMID- 14650162
TI  - [Study of X-irradiation to enhance the functional and structural recovery of the
      injured spinal cord of rat].
AB  - OBJECTIVE: To explore whether X-irradiation can enhance the functional and
      structural recovery of the injured spinal cord of rats. METHODS: Seventy Sprague
      Dawley rats received spinal cord injury by clip compression at the T2 level were
      randomly divided into two groups. The experimental group received X-irradiation
      at 14 days after injury, the control group did not receive X-irradiation. The
      functional tests were performed at day 3, 7, 14, 21, 28, 35, and 42 after
      irradiation including open field movement, inclined plane and pain withdrawal
      test. All injured rats were sacrificed at 43 days after injury and the injured
      spinal cords were taken out for histological tests. RESULTS: Sixty-two rats met
      the experimental requirements among 70 injured rats, 32 rats in experimental
      group and 30 rats in control group. Statistically significant difference was
      achieved between two groups in open field movement and inclined plane (P < 0.01),
      but not for the pain withdrawal test. The edema and necrosis area of injured
      spinal cords of experimental group were less than those in control group, and the
      number of axons of experimental group were more than those in control group.
      CONCLUSIONS: X-irradiation can enhance the functional recovery by improving and
      restoring structural integrity of the injured spinal cord.

PMID- 14650163
TI  - [Translocation between chromosomes 4q35 and 10q26 in facioscapulohumeral muscular
      dystrophy].
AB  - OBJECTIVE: To investigate the distribution of translocation between chromosomes
      4q35 and 10q26 in facioscapulohumeral muscular dystrophy (FSHD) patients and
      normal individuals. METHODS: The Bgl II-Bln I dosage test was performed to study
      the distribution of translocation between chromosomes 4q35 and 10q26 in 70 cases
      of FSHD patients, 55 cases of kindred with FSHD, and 52 cases of normal controls.
      RESULTS: (1) In normal individuals, the frequency of translocation between
      chromosomes 4q35 and 10q26 is 19.23%. The frequency of translocation from
      chromosome 4q35 to 10q26 and that from chromosome 10q26 to 4q35 are both 9.62%.
      (2) In the FSHD patients, the frequency of translocation between chromosomes 4q35
      and 10q26 is 18.57%. The frequency of translocation from chromosome 4q35 to 10q26
      and that from chromosome 10q26 to 4q35 are 12.86% and 5.71% respectively.
      CONCLUSIONS: The translocation between chromosomes 4q35 and 10q26 was frequently
      observed in both normal Chinese population and FSHD patients. No significant
      difference was observed between them.

PMID- 14650164
TI  - [Static and dynamic contrast sensitivity of myopic eyes before and after laser in
      situ keratomileusis].
AB  - OBJECTIVE: To evaluate the static and dynamic contrast sensitivity changes in
      myopic patients before and after laser in situ keratomileusis (LASIK). METHODS:
      Seventy-three eyes in 37 patients with myopia (with or without astigmatism) who
      received LASIK were tested for static and dynamic contrast sensitivities using
      the METRO VISION MON ELEC I system at 0.7, 1.4, 2.7, 5.5, 11, and 22 cpd and cps
      prior to LASIK, and at one-, three-, and six-month intervals after LASIK.
      RESULTS: All eyes gained naked visual acuity of more than 0.5 after LASIK. The
      contrast sensitivity was depressed at all frequencies 1 month after LASIK, as
      compared to one week prior to LASIK. The depression at 2.7, 5.5, 11 (P < 0.01)
      and 22 cpd (P < 0.05) was statistically significant for static contrast
      sensitivity, and also at 5.5 (P < 0.01) and 11 cps (P < 0.05) for dynamic
      contrast sensitivity. Myopic eyes between 6.25 D and 14.0 D, and astigmatic eyes
      2 DC and more, suffered more static and dynamic contrast sensitivity depression
      than the myopic eyes between 1.25 D and 6.00 D and astigmatic eyes less than 2
      DC. Contrast sensitivities were improved and exceeded preoperative levels 3
      months after LASIK, and improved even more 6 months after LASIK. All sequences
      were statistically significant for static contrast sensitivity (P < 0.01), while
      only 2.7, 5.5, and 11 cps were statistically significant for dynamic contrast
      sensitivity (P < 0.01). The astigmatic eyes 2 DC and more showed less
      improvement, even below the preoperative level at 1.4 cps of dynamic contrast
      sensitivity. CONCLUSIONS: While temporary depression of contrast sensitivity for
      myopic eyes after LASIK was seen, contrast sensitivity soon returned to exceed
      preoperative levels at 3 months after LASIK, while improving even more 6 months
      after LASIK.

PMID- 14650165
TI  - [Analysis of 602 cases of nevus of Ota and study of ultrastructures on the
      melanocytes].
AB  - OBJECTIVE: To analyze clinical information and efficacy of 602 cases of nevus of
      Ota, and investigate the histopathology and ultrastructure on the melanocytes
      before and after Q-switched Alexandrite laser irradiation. METHODS: Clinical
      information of 602 cases of nevus of Ota were collected by applying clinical
      records, checking photos, and inquiry to patients by letters and telephones. Ten
      cases of biopsies were observed by light microscopy and 6 cases by electron
      microscopy before and after laser irradiation. RESULTS: Nevus of Ota included
      congenital and acquired cases. Skin lesions mainly occurred in adolescence for
      the acquired cases. The main colours of lesions were brown and blue. The most
      local lesions were zygomata, temporal regions, and lower eyelids. According to
      multiple regression, the more treatment times, the better results. The effective
      rate was 85.20% and 100% after 6 and 9 treatment times, respectively, while the
      cure rate was 55.72% and 98.46%, respectively. The eyelids involved and Tanino
      types influenced the treatment times by COX models analysis. Electron microscopy
      showed many melanosomes in the dermal melanocytes. After laser irradiation, the
      outlines of the dermal melanocytes were observed, the melanosomes were broken to
      dense and tiny granules. CONCLUSIONS: Q-switched Alexandrite laser is safe and
      effective for the treatment of nevus of Ota. The results of treatment are
      correlated with the area and size of the lesion. The dermal melanocytes in nevus
      of Ota can be selectively destroyed by Q-switched Alexandrite laser with less
      injury around tissues.

PMID- 14650166
TI  - [Perioperative melatonin secretion rhyme in patients undergoing coronary artery
      bypass grafting surgery].
AB  - OBJECTIVE: To investigate perioperative patterns of melatonin and cortisol
      secretion rhyme in patients undergoing coronary artery bypass grafting surgery.
      METHODS: Eleven male patients scheduled for elective coronary artery bypass
      grafting surgery (CABG) under hypothermic cardiopulmonary bypass (CPB) were
      enrolled in the study. Anesthesia was induced and maintained with propofol (3
      mg.kg-1.h-1) and supplemented with fentanyl (15 micrograms/kg). Blood samples
      were taken during surgery at specific time-points and every 3 h in the immediate
      postoperative period and postoperative day 2 and day 3. Plasma melatonin and
      cortisol levels were measured by radioimmunoassay and enzyme-linked immunosorbent
      assay respectively. RESULTS: During surgery, plasma melatonin levels were below
      the minimum sensitivity level but low levels, without circadian variation, were
      measured during the immediate postoperative period. During postoperative day 2
      and day 3, circadian secretion patterns of melatonin were present in 10 patients
      and showed an inverse correlation with light intensity exposed (r = -0.480, P =
      0.01). Plasma cortisol levels in the immediate postoperative period were
      significantly higher than those before induction of anesthesia (P < 0.01). During
      postoperative day 2 and day 3, only 3 patients regained circadian secretion of
      cortisol. CONCLUSIONS: It is concluded that melatonin and cortisol secretion are
      disrupted during cardiac surgery and in the immediate postoperative period.

PMID- 14650167
TI  - [Estimation of expression of glycosylphosphatidylinositol-anchored protein in B
      lymphocytes for diagnosis of paroxysmal nocturnal hemoglobinuria].
AB  - OBJECTIVE: To estimate whether the expression of glycosylphosphatidylinositol
      (GPI)-anchored protein in B lymphocytes could be an indicator for detecting
      paroxysmal nocturnal hemoglobinuria (PNH). METHODS: Flow cytometry and two-color
      McAbs were used to detect CD59 expression in B lymphocytes and granulocytes of 92
      clinical samples. The feasibility of the indicators for diagnosis of PNH was
      assessed. RESULTS: B lymphocytes from healthy individuals mainly showed a single
      population of cells strongly positive for CD59, as the percentage of CD59
      expression was (96.3 +/- 1.2)%. In PNH patients, B lymphocytes showed decreased
      expression of CD59, as well as negative cells and partly-positive cells were
      observed, as the percentage of CD59 expression was 10.5%-92.3%. In 26 of 28 non
      PNH anemia patients, CD59 expression in B lymphocyte was normal, and in the other
      2 patients, CD59 expression were decreased (< 95%), but no negative cell peak was
      observed. The precision CV of CD59 in B lymphocyte assay is less than 4.4%,
      stained samples could be kept stable for 24 h, the CD59 in B lymphocyte assay was
      100% in accordance with routine assay (CD59 in granulocyte assay). The
      sensitivity of the indicators (CD59 in B lymphocytes and granulocytes) was 100%,
      the specificity was 97.4%, misdiagnosis rate was 2.6%, the rate of failing to
      diagnosis was 0%, the rate of positive forecast was 87.5%, the rate of negative
      forecast was 100%, the accuracy was 97.8%. CONCLUSIONS: The test of CD59
      expression in B lymphocytes by flow cytometry was simple, accurate and
      reproduceable. It could be a good marker for diagnosis of PNH because of high
      sensitivity and specificity.

PMID- 14650168
TI  - [Abnormal interferon-inducible protein-10 expression in the labial glands of
      patients with Sjogren's syndrome].
AB  - OBJECTIVE: To investigate whether interferon-inducible protein 10 (IP-10) is
      involved in the inflammatory process of the labial gland of patients with
      Sjogren's Syndrome (SS). METHODS: Forty-nine patients performed labial gland
      biopsy, the number of lymphocytes in the biopsy tissues was calculated and the IP
      10 was detected by the methods as following: 39 biopsied labial tissues were
      examined by RT-PCR, among them, 21 were from primary SS, 5 from secondary SS and
      13 from other diseases. With RT-PCR, the IP-10 and beta-actin were co-amplified
      with specific primers. The gel-fractioned and ethidium bromide amplification
      products were then analyzed by densitometry. The expression of IP-10 was semi
      quantificated by IP-10/beta-actin ratio. Twenty-one samples were examined by
      immunohistochemistry with specific goat anti-IP-10 antibody, 10 of them from
      primary SS, 3 from secondary SS, 8 from other diseases. 11 out of 21 samples were
      examined by both RT-PCR and immunohistochemistry. RESULTS: The expression of IP
      10 mRNA was significantly up-regulated in labial glands of patients with SS
      compared with other diseases (IP-10/beta-actin ratio was 0.329 +/- 0.157 vs 0.099
      +/- 0.059, P < 0.01). The number of lymphocyte infiltration foci in labial glands
      of patients with SS correlated to the IP-10/beta-actin ratio (r = 0.657, P <
      0.05). Ductal epithelial cells and some of the infiltrating lymphocytes were
      stained by anti-IP-10 antibody by immunohistochemistry in 8 of the primary SS
      (8/10), all of the secondary SS (3/3) and one with primary biliary sclerosis
      (1/8). The expression of IP-10 protein detected by immunohistochemistry was
      consistent with that of mRNA detected by RT-PCR. CONCLUSIONS: IP-10 is abnormally
      highly expressed in the labial glands of patients with SS and positively relates
      to the lymphocyte infiltration. It thus suggests chemokine IP-10 may be one of
      the important molecules attracting the lymphocytes to the minor salivary glands
      to form the lymphocytic foci of Sjogren's Syndrome.

PMID- 14650169
TI  - [Imaging diagnosis of mucinous cystic neoplasms of the pancreas].
AB  - OBJECTIVE: To assess the imaging findings in mucinous cystic neoplasms (MCNs) of
      the pancreas. METHODS: The imaging manifestations of 18 cases with pathologically
      proven MCNs were analyzed retrospectively. RESULTS: The cystic features of MCNs
      could be demonstrated by ultrasonography (US), computed tomography (CT), or
      magnetic resonance imaging (MRI). Compared with US, CT and MRI are appropriate
      for localizing diagnosis (100%). One half of the cases have classic imaging
      findings of the MCNs, where as the diagnosis of remaining cases could be
      supported by clinical findings. CONCLUSIONS: Imaging technique plays an important
      role in the diagnosis of MCNs.

PMID- 14650170
TI  - [Effect of nitric oxide in vestibular compensation].
AB  - OBJECTIVE: To study the effect of nitric oxide (NO) in vestibular compensation
      after unilateral vestibular deafferentation. METHODS: Eighteen animals were
      divided into two groups, 6 of group a as control, 12 of group b received
      gentamicin intratympanic injection in the left ear. Half of the animals were
      killed respectively after 5 days and 10 days. Vestibular endorgan and brainstem
      tissue sections were subjected to NADPH-d reactive test of NOS for histochemical
      examination. RESULTS: In group a, NOS-like reactivity in both sides of vestibular
      endorgan and nucli. In group b during 5 days, NOS-like reactivity in right side
      of vestibular endorgan and nucli, those of the left side were negative. During 10
      days, NOS-like reactivity only in the right side of vestibular endorgan.
      CONCLUSIONS: Changes of NOS expression in the contralateral vestibular nucli
      might have played a role in vestibular compensation.

PMID- 14650171
TI  - [Influence of obesity on pharmacokinetics and pharmacodynamics of isoflurane].
AB  - OBJECTIVE: To observe the effect of obesity on pharmacokinetics and
      pharmacodynamics of isoflurane. METHODS: Twenty-six patients undergoing
      cholecystectomy were divided into obese group (Group A, BMI > or = 27, n = 13)
      and normal body weight group (Group N, BMI < or = 24, n = 13) according to body
      mass index (BMI). All patients were given to the same isoflurane anesthesia.
      Inspired and end-expired concentrations of isoflurane were monitored and uptake
      fraction of isoflurane were calculated. RESULTS: Isoflurane concentrations of
      vaporizer in Group A [(1.8 +/- 0.3)%] were evidently higher than those in Group N
      [(1.5 +/- 0.1)%] at all observed points (P < 0.05 or P < 0.01). Uptake fraction
      of isoflurane in Group A were higher than those in Group N at observed points (P
      < 0.05, P < 0.01 or P < 0.001), but there were no differences in the time when
      isoflurane concentration was lowered to 50% and awake time between the two groups
      after discontinuing inhaling isoflurane. CONCLUSIONS: Obese patients demand
      higher inspired concentration and uptake of isoflurane than those in normal
      weight patients but discharge of isoflurane was influenced by obesity within the
      observed period of (66 +/- 33) min.

PMID- 14650172
TI  - [Cleft lip nasal deformity corrected by an alar flap and the alar cartilage sling
      method].
AB  - OBJECTIVE: To search an effective method to correct the secondary nasal
      deformity. METHODS: The "spilth" tissue asymmetry to the another side on the
      cleft side alar is formed as a flap, which is used to drive up or reconstruct the
      nostril base (sill), readjust nostril size and shape. The cleft side alar
      cartilage lateral foot is disassociated, replaced and fixed into the normal
      place. RESULTS: Nineteen patients were received this operation, their nasal alar,
      nostril, sill, on the two sides are symmetry, and the result is good.
      CONCLUSIONS: The cleft side alar flap and alar cartilage sling procedure is
      effective to correct secondary cleft lip nasal deformity.

PMID- 14650173
TI  - [Diagnosis and surgical treatment of carotid body tumour].
AB  - OBJECTIVE: To discuss the diagnosis and surgical treatment of carotid body
      tumour. METHODS: Thirty-eight cases (41 carotid body tumours) admitted from 1983
      to 2002 were analyzed retrospectively. RESULTS: All patients were examined by
      ultrasound and angiography routinely before operation. The diagnostic coincidence
      rates of ultrasound and angiography are 95% and 98% respectively. Thirty-eight
      tumours were resected successfully. Twelve patients underwent external carotid
      artery severed, internal carotid artery repaired and tumour resected operation.
      Eleven patients underwent external carotid artery severed and tumour resection.
      Eight patients underwent tumour simple resected operation. Six patients underwent
      external carotid artery severed and internal carotid artery reconstruction. One
      patient underwent tumour resection, while common, external, and internal carotid
      artery were partially resected. CONCLUSIONS: For suspected carotid body tumour
      patients, ultrasound and angiography reconstruction of carotid artery should be
      applied routinely before operation. The early stage and one stage tumour resected
      operation as well as internal carotid artery reconstruction are the key factors
      of decreasing operative complication rate.

PMID- 14650174
TI  - [Thyroid nodules with calcification and thyroid carcinoma].
AB  - OBJECTIVE: To investigate the significance of thyroid calcification for diagnosis
      of thyroid carcinoma. METHODS: Retrospective analysis of 817 thyroid nodules' pre
      operative ultrasonic and postoperative pathologic results. RESULTS: Total
      ultrasonic thyroid calcification ratio was 18.1% (148/817). Total pathologic
      thyroid calcification ratio was 19.6% (160/817), which in benign samples was
      lower than that in malignant samples (13.1% vs 53.5%, P < 0.01). Micro
      calcification ratio in benign samples was lower than that in malignant samples
      (2.9% vs 38.6%, P < 0.01). CONCLUSIONS: Thyroid nodules with calcification
      especially micro-calcification is considered to be the most specific sign of
      thyroid carcinoma, so the detection of it should be an important diagnostic
      criterion.

PMID- 14650175
TI  - [Latent autoimmune diabetes in adults: an update].
AB  - Latent autoimmune diabetes in adults (LADA), presenting with a similar phenotype
      of type 2 diabetes at early stage, belongs to the slowly progressive subtype of
      autoimmune type 1 diabetes. LADA differs from classic juvenile-onset type 1
      diabetes in which its autoimmune destructive process of islet beta-cells is much
      slower, so LADA may serve as a human model of autoimmune type 1 diabetes.
      Although no international standardized criteria for the diagnosis of LADA has
      been established, it should be noted that LADA has some specific features in
      clinical characteristics, susceptible genotypes, cellular and humoral immune
      markers, as well as islet pathology. Presence of islet autoantibodies is
      necessary for the diagnosis of LADA. Early insulin intervention may preserve
      residual islet beta-cell function in LADA. The different pathological
      manifestations of LADA with different autoantibody titers can help throw light on
      the autoimmune process, laying foundation of prevention or even cure of type 1
      diabetes.

PMID- 14650176
TI  - [CCR5, a new target of anti-HIV drugs].
AB  - CCR5, a membrane protein on cell surface, is a member of the G protein-coupled
      receptor superfamily and one of the major co-receptors for HIV-1 infection. The
      roles of CCR5 in HIV-1 infection have been elucidated since 1996. Because of the
      biological nature of CCR5, it has became a molecular target for the novel drugs
      against HIV-1. Antagonists for CCR5 could be grouped as following, chemokine
      derivatives, small molecule non-peptide compounds, monoclonal antibodies and
      peptides. The latest progress in this field is reviewed in this article.

PMID- 14650177
TI  - [Preparation methods of nanocavity biomaterials with recognition specificity via
      template imprinting of proteins].
AB  - Nanocavity biomaterials with recognition specificity imprinted by using proteins
      as templates may successful serve as substitutes for antibodies, enzymes, and
      other native biological structures as well as cell bracket materials. It has
      numerous applications in biotechnology, medicine and so on. In this paper, the
      principle of template imprinting is introduced briefly, the specialty of template
      imprinting of proteins is analyzed, and the methods of template imprinting of
      proteins including protein entrapment, microbead surface imprinting, flat surface
      imprinting as well as the epitope are reviewed in details.

PMID- 14650178
TI  - [Effects of manganese with different valences to apoptosis of SH-SY5Y cell].
AB  - To study the effect of manganese with different valences to apoptosis, human
      neuroblastoma cell line (SH-SY5Y) has been chosen to study the induction of Mn2+
      and Mn3+ on apoptosis and the content of dopamine in vitro. The results showed
      that both Mn2+ and Mn3+ induced a time-dependent decrease in SH-SY5Y cell
      viability, as determined by MMT assay. In the meantime, apoptosis was inducted by
      flow cytometer analysis (FCAS) after culture of Mn2+ or Mn3+ (0.5-2 mmol/L) with
      SH-SY5Y cell for 24-72 h. The ultrastructural changes of apoptosis such as
      nuclear chromosome condensation, was seen by transmission electron microscope. In
      addition, DA content was decreased by measured with HPLC. The major path of cell
      death induced by Mn2+ and Mn3+ may be due to apoptosis. Both Mn2+ and Mn3+ could
      induce the reduction of DA content. All these results suggest that Mn3+ appeared
      to be more cytotoxic than Mn2+.

PMID- 14650179
TI  - [Levels and distribution of 15 rare earth elements in tumor and normal lung
      tissue from the patients with lung cancer].
AB  - Ten tumor tissue and normal tissue around tumors were collected from the patients
      with lung cancer. After digested by mixed acids(HNO3:HClO4 = 10:1), 15 rare-earth
      elements (REEs) in the tissue were measured directly by ELAN 5000 ICP-MS. Tissue
      levels and distribution of 15 REEs were analyzed and compared with those in
      healthy human lung tissue measured in the same condition. Re (rhenium) was used
      as an internal standard element to compensate for matrit inhibition and
      sensitivity drift. Recoveries of standard addition for REEs was 92.9%-111.3% and
      the precision was 0.96%-3.07%. Results showed that levels of 15 REEs in normal
      tissues around the tumor was as 2.07-2.51 times high as those in the tumor
      tissue, while the REE distribution curves of them was similar. There were
      positive abnormalities of Ce and negative abnormalities of Eu in REE curves of
      both tissue after chondrite-normalized. Compared REE level and distribution
      pattern in normal tissue with those in tumor tissue from patients with lung
      cancer, it was found that contents of light REE in lung tissue of health human
      were much higher while the contents of media and heavy REE were much lower.
      LREE/HREE in the tumor tissue and normal tissue with lung cancer and health human
      lung tissue were 12.99, 13.72 and 44.11 respectively. This study suggested that
      there might be light REEs accumulation in human lung tissue compared with REE
      distribution in the air particulates and soil. Light REEs accumulation in the
      lung of healthy people was more obviously than that in patients with lung cancer.

PMID- 14650180
TI  - [Effect of the long-term intake of yttrium in drinking water on trace elements in
      F1 generation mice].
AB  - The effects of the long-term intake of yttrium on trace elements in tissues and
      yttrium in brain of F1 generation mice were studied so as to elucidate some
      physiological function of the rare earths. The mice were fed with Y3+ (0, 23.25
      mg/L, 2325.00 mg/L) dissolved water at different levels for seven months. The
      level of trace elements such as Cu, Cd, Pb and Y in brain and Se in brain, liver,
      spleen and kidney of F1 generation mice were measured by ICP-MS and atom
      fluorescent method. The results showed that, compared with control mice,
      significant changes in content of Se (P < 0.05) in spleen and Y (P < 0.05) in
      brain were observed, but no changes were found in content of Pb, Cd, and Cu in
      brain for the high dose group, and an increase was detected in content of Se(P <
      0.05) in spleen for the low dose group, suggesting that long-term intake of Y3+
      might enhance the absorption of Se in some tissue that might be one of the
      biological effect of rare earth and, Y3+ might enter young mammalian brain.

PMID- 14650181
TI  - [Application of precision-cut liver slice to the study of the effect of
      glutathione on cadmium chloride hepatotoxicity].
AB  - In order to evaluate the feasibility of application of precision cut liver
      slice(PCLS) to the study of the effect of glutathione on cadmium chloride
      hepatotoxicity, slices were cultured with CdCl2 and GSH. Slices activity and drug
      metabolic function was estimated by assay of slice viability, NO secretion, and
      phase I and phase II enzyme activity. Results showed that the slices activity was
      significantly inhibited by CdCl2. Various phase I and phase II enzymes activity
      of slices were obviously reduced by CdCl2, but aniline hydroxidase activity was
      enhanced. GSH could distinctly reversed the change of slices induced by CdCl2.
      Therefore, it could be concluded that PCLS culture system was sensitive and
      steady, and was a good model for pharmacological and toxicological investigation
      of liver in vitro.

PMID- 14650182
TI  - [Effects of fluoride on cell cycle and apoptosis in cultured osteoblasts of
      rats].
AB  - To study the effects of fluoride on cell growth, cell cycle and apoptosis in
      cultured osteoblasts of rats. The enzymes digesting method was used to isolate
      the osteoblasts of rats. The activity of the cells was determined by the percents
      of reduced AlamarBlue. FCM was used to analyze cell cycle and apoptosis. The
      results showed that the activity of rat osteoblast was not influenced by NaF at 0
      to 2 mmol/L concentration after 24 hours incubation. At the concentration of 2
      mmol/L, the number of cells at S phase was increased. At the concentration of 4
      mmol/L, NaF increased the number of cells at S phase and at the same time,
      decreased the number of cells at G2/M phase, but the number of the cells at G0/G1
      phase kept unchanged. The percent of apoptosis was increased at the concentration
      of 2 mmol/L. Excessive fluoride could affect the cell activity, retarded cell
      cycle at S phase and induced apoptosis.

PMID- 14650183
TI  - [An experimental study of the effects of profenofos on antioxidase in rabbits].
AB  - In order to explore the effects of superoxide dismutase(SOD), catalase(CAT),
      glutathione-peroxidase (GSH-Px) in rabbits exposed by profenofos and its meaning.
      18 rabbits were divided into three groups randomly: A group (high-dose group), B
      group(low-dose group), C group(control group), each group including 6 rabbits.
      The activities of SOD, CAT, GSH-Px in plasma, and cholinesterase(ChE) in blood
      were measured in different exposure period. The results showed that activities of
      SOD, CAT and GSH-Px increased, ChE decreased markedly compared with those in the
      same group before experiment and control group (P < 0.05, P < 0.01). The increase
      of antioxidase activities was earlier than the decease of ChE activity. It
      suggests that profenofos can result in the increases of the activities of SOD,
      CAT and GSH-Px, which may be earlier diagnostic index in profenofos poisoning.

PMID- 14650184
TI  - [Relations between trace elements in drinking water and elderly residents'
      cognitive function].
AB  - The relationship between trace element levels in drinking water and cognitive
      function was studied for elderly residents in rural areas in China. Cognitive
      function was measured by a Chinese translation of the Community Screening
      Interview for Dementia (CSI "D"). The trace elements fluoride, calcium, selenium,
      aluminum, iron, zinc, cadmium, lead and arsenic contents of drinking water were
      determined using Chinese. National Standard Methods. A mixed effects model was
      used to evaluate the effect of each of the elements on cognitive function while
      adjusting for age, sex, and education level. Several of the elements examined had
      a significant effect on cognitive function when they were examined in a
      univariate context. However, after adjusting for other elements many of these
      results were not significant. There was a significant quadratic effect for
      calcium and a significant zinc-cadmium interaction. Cognitive function increased
      with calcium level to a certain point, and then decreased as calcium continued to
      increase. Zinc showed a positive relationship with cognitive function at low
      cadmium levels, but a negative relationship at high cadmium levels.

PMID- 14650185
TI  - [Effect of lycopene on the function of antioxidative enzyme system in rats].
AB  - In order to observe the effect of Lycopene(LP) on antioxidation in rats, the rats
      were given LP by oral. After 4 weeks the activity of SOD, MDA and GSH-Px, T-AOC,
      GSH, CAT in serum and liver were measured respectively. The result showed that
      the activities of SOD, T-AOC and GSH-Px in LP group were increased and the
      concentrations of MDA were decreased significantly(P < 0.05) compared with
      control group. LP could increase antioxidative effect and reduce lipid
      peroxidation in Wistar rats.

PMID- 14650186
TI  - [Relationship between calcium content and its character in fetal tissues and
      calcium deficiency of minor].
AB  - In order to probe the relationship between calcium content and its status in
      fetal tissue and minor's calcium deficiency, the calcium content of seven tissues
      of fetus aged 4 to 10 month was measured and analyzed. Results showed that the
      calcium content in fetal tissues was an unstable variable, and it was a function
      of spatio-temporal factors. Calcium content in fetal tissues reduced with the
      increase of age and weight of tissue, making a continuous decrease of the calcium
      content in per gram tissue. This characteristic could last to about the age of 20
      years old of children. The physiological character that calcium content in
      tissues of fetus and minor decreases with the development can make people to be
      more aware to calcium deficiency, laying the physiological basis of calcium
      deficiency of the people in low age, providing the physiological information for
      adjusting and controlling the calcium nutrition of the fetus, minor and pregnant
      woman.

PMID- 14650187
TI  - [Effect of iron on peroxidation and non-enzymatic glycation in diabetic rats].
AB  - SD rats were peritoneally injected with streptozotocin to establish diabetes
      mellitus animal model. The changes of nonenzymatic glycation and peroxidation in
      rats supplemented with low iron high iron during five weeks were investigated. It
      was found that MDA in serum or renal cortex but not glycated hemoglobin, glycated
      LDL, renal cortical AGEs increased significantly after supplementation of high
      iron in diabetic rats. There was no change in serum MDA, renal cortical MDA,
      glycated hemoglobin, glycated LDL and AGEs after supplementation of low iron in
      diabetic rats. The results suggested that peroxidation could be enhanced
      obviously by supplementation of high iron so that chronic complications could be
      promoted by high dose iron in diabetic rats.

PMID- 14650188
TI  - [Effects of soybean phospholipid on the content of malondialdehyde and lipofuscin
      in heart, liver and spleen in mice].
AB  - In order to observe the effects of soybean phospholipids on the SOD activity in
      liver and the content of malondialdehyde and lipofuscin in heart, liver and
      spleen in mice, forty male mice were divided into 4 groups. Experimental mice
      were fed with different doses of soybean phospholipids (2.5, 5 and 10 g/kg BW)
      and the control mice were fed with normal saline by tube feeding for 18 days.
      After that, the SOD activity in liver and the content of malondialdehyde and
      lipofuscin in heart, liver and spleen were measured. The results showed that the
      three doses of soybean phospholipid could significantly increased the SOD
      activity of liver (P < 0.05), and also could remarkably decrease the
      malondialdehyde content of in heart(P < 0.01) and in liver (P < 0.05). The
      soybean phospholipid at dose of 2.5 g/kg BW could significantly decrease the
      malondialdehyde content of in spleen(P < 0.05). But the three doses of soybean
      phospholipid did not obviously affect the content of lipofusin in liver, heart
      and spleen. The study indicated that the soybean phospholipid was effective on
      the inhibition of lipid peroxide.

PMID- 14650189
TI  - [Preparation of fiber complexes and its role in lipid peroxidation].
AB  - This study was designed to prepare the artificial fiber complexes and examine its
      role in lipid peroxidation in comparison with other fibers. Sixty-four healthy,
      female Wistar rats (50-80 g) were randomly divided into eight groups based on
      body weight. All seven kinds of DF (cellulose--group B, pectin--group C, sodium
      alginate--group D, cellulose-pectin complex--group E, cellulose-sodium alginate
      complex--group F, cellulose-pectin mixture--group G, cellulose-sodium alginate
      mixture--group H) were given at a level of 10% in the diet fed on a lipid-rich
      diet. The control group (group A) was fed on a lipid-rich diet alone without DF.
      After eight weeks, the effect on growth and development, lipid metabolism and
      lipid peroxidation in rats were studied. The results showed that: 1. Seven kinds
      of DF did not affect the growth and development of the experimental rats. 2.
      Seven kinds of DF all can increase serum superoxide dismutase (SOD) and
      glutathione peroxidase (GsH-Px) activities and reduce malondiadehyde (MDA)
      content (except group B and D). Erythrocyte membrane fluidity was significantly
      increased in DF groups, and fiber complex groups were most effective. 3. The
      fecal weight and fat contents in all DF groups were significantly higher than
      that in control group, especially for fiber mixture and complex groups. It is
      concluded that all these kinds of DF have the effect of reducing lipid
      peroxidation to some extent in rats, and fiber complexes might be the most
      effective.

PMID- 14650190
TI  - [Study on the effect of micronutrients supplementation on health status of
      children].
AB  - To study the effect of multi-micronutrients supplementation on nutritional status
      of children, 220 students aged 8-12 years were observed for 6 months. A half of
      them were given the supplements, another half placebo. The results showed that in
      comparison with the placebo, the supplemented children had a higher urine
      excretion of vitamin B2 and vitamin C after loading; a higher concentration of
      serum 25-OH-D3, a high content of hydroxy-proline and hydroxy-proline/creatinine
      ratio in fast urine, and a higher bone mineral content and bone mass density of
      the mid-ulna. The supplemented children performed significantly better than the
      placebo in reading speed, learning capacity and arithmetic examinations. It is
      concluded that micronutrients supplementation played a notable rule in resulting
      better nutritional status and learning ability of school children.

PMID- 14650191
TI  - [Impact of supplementation of vitamins and minerals on nutritional status of
      women in suburb].
AB  - In order to investigate the effect of vitamins-minerals supplementation on the
      nutritional status of Chinese women, 252 villagers aged 20-50 years old were
      selected as the participants in the study in Longli County, Guizhou Province.
      Within Twenty two weeks, half of the participants received the supplements and
      half had placebo. The results showed that in comparison with the control, the
      women with supplementation represented a higher urine excretion of vitamin B1 and
      B2 after a loading dosage and, a higher concentration of serum iron and zinc and
      a lower prevalence of anemia. They kept their facial moisture and grease better
      than those of the controls. They also felt better in sleeping, having appetite,
      and doing physical activities. The results indicated that the supplementation of
      vitamins-minerals might improve the nutritional status of rural Chinese women.

PMID- 14650192
TI  - [Study on dynamic changes of body mass index for adults in Henan Province].
AB  - To analysis the dynamic changes of body mass index (BMI) of adults, and provide
      basis for health research and policy-making, using the random cluster sampling, a
      total of 480 households (urban 80, suburban 80, county neighboring communities
      80, rural 240) in 24 different sites were selected. The adults of selected
      households were subjects. Data on height, body weight and household income etc
      were collected in autumn of every surveying year. The results showed that the
      rates of BMI < 18.5 cut-off point declined with years, they were 7.3% and 3.5% in
      1989 and 2000 respectively. The rates of overweight and obesity showed a steadily
      increasing tendency, rose up sharply from 10.7% in 1989 to 25.2% in 2000, about
      1.5% higher each year. The percentage of overweight and obesity altogether in
      2000 ranked as urban 33.3%, county 31.7%, suburban 24.6%, and rural 21.4%. It
      suggested that the percentage of overweight and obesity increased quickly, have
      accounted for big part in population, and should be listed as one of major public
      health issues.

PMID- 14650193
TI  - [Study on the energy expenditure in college students in Guangdong Province].
AB  - To investigate the energy expenditure of college students, 61 college students
      (30 male and 31 female) in Guangdong were selected as the participants. Basal
      metabolism was measured by indirect calorimetry. The activities of college
      students were systematically recorded using 24 hours recall method. Total energy
      expenditure was evaluated by the factorial calculation method of WHO. RESULTS:
      Basal metabolism rates of male and female college students were (158.03 +/- 7.85)
      kJ/(m2.h) and (145.05 +/- 10.14) kJ/(m2.h) respectively. Total energy expenditure
      of 24 hours were (10389.23 +/- 1519.90) kJ/d and (7921.15 +/- 961.41) kJ/d
      respectively. CONCLUSION: The energy expenditure of college students in South
      China accorded with the criteria of "Chinese adults at light physical activity
      level".

PMID- 14650194
TI  - [Pollution of EHEC O157:H7 in six types of food in Henan Province].
AB  - In order to investigate the distribution of contamination of EHEC O157:H7 in 6
      types of food in Henan Province and characterize the effect of seasonal factors
      on distribution of O157:H7 contamination so as to prevent and control food
      contamination, Henan Province was divided into five sampling areas according to
      the natural geographical features. Samples were taken randomly in summer and
      winter sales links. After selective culture of increasing reproduction of
      O157:H7, it was screened by immuno-gold reagent, and pathogenic bacterium were
      isolated after accumulation of immunomagnetic. Then, it was identified by the
      bioMerieux VITEK32 AMS system, GNI+ and sero-reaction. Results showed that 28
      EHEC O157:H7 were isolated in 1463 samples among which the positive rate of raw
      meat and fresh vegetable was 3.3% and 3.2% respectively (the highest of all), and
      EHEC O157:H7 was not found in yogurt. The positive rate in summer (2.5%) was
      obviously higher than that in winter (1.1%). It could be concluded that the
      contamination of EHEC O157:H7 in food was serious. Its positive rate was
      positively correlated with the epidemic of infective diarrhea. Therefore,
      attention should be given by relevant departments concerned and spervision and
      testing should be strengthened in livestock and farmyard bird slaughtering link,
      vegetable production link and sales link for better prevention of the breaking
      out and epidemic of food born diseases.

PMID- 14650195
TI  - [Assessing the content of formaldehyde in vermicelli in Changsha market].
AB  - In order to better supervise food safety for the residents, the extent of
      formaldehyde in vermicelli sold on Changsha market was assessed by the acetyl
      acetone colorimetry method. Results showed that among 106 samples, 61 were
      formaldehyde positive. The positive rate was 57.55% (61/106). The content of
      formaldehyde ranged from 0.011 mg/kg to 2.859 mg/kg, indicating severe
      contamination of vermicellis by formaldehyde in Changsha market and therefore,
      the food safety supervision work should be strengthened.

PMID- 14650196
TI  - [Evaluation on the effects of community-based anti-smoking intervention].
AB  - To explore effective antismoking intervention measures, measures including flyers
      and booklets as major mass media, school-based health education and follow-up to
      smokers were carried out in Beijing, Shanghai and Changsha urban communities. The
      changes of smoking behavior in population were evaluated by quasi-trial
      designation. Results showed that smoking rates in adult male, female and both
      genders decreased by 5.54%, 2.61% and 2.94% respectively and were statistically
      significant in intervention community. Compared with control community, the net
      decrease of smoking rates in adult male, female and both were 4.90%, 3.37% and
      3.51% respectively. The net increase of quitting rates in adult male, female and
      both were 4.35%, 17.19% and 6.30% respectively. The net changes in female and in
      both genders of smoking and quitting were all statistically significant. It was
      suggested that comprehensive intervention measure with health education as the
      core might be the priority for the effective community-based antismoking
      activity. The policy-making and behavior encouraging activities should be
      focused.

PMID- 14650197
TI  - [Study on the blood glucose and lipid of soybean milk rich in chromium to
      diabetic rats].
AB  - To reveal the effects of soybean milk with chromium fortification on the blood
      glucose and lipid of diabetic rat dealt with alloxan. The alloxan diabetic rats
      were divided into three groups and were fed continuously with the soybean milk
      without chromium fortification [Cr 0.25 microgram/(d.kg BW)], and with low
      chromium [Cr 30 micrograms/(d.kg BW)] and high chromium fortification [Cr 300
      micrograms/(d.kg BW)] respectively for four weeks. The blood samples from all
      experimental rats tail vine were obtained each week. Blood glucose, total
      cholesterol, triglyceride, very low-density lipoprotein, high-density lipoprotein
      and insulin were tested. RESULTS: The concentrations of blood glucose, total
      cholesterol, triglyceride, very low-density lipoprotein and insulin were lowered
      significantly, and high-density lipoprotein was elevated significantly in the
      rats fed by soybean milk with high chromium fortification during the experimental
      period. The effect of improving blood glucose concentration in the group of
      soybean milk with high chromium fortification is significantly better than that
      in other groups. CONCLUSION: The present investigation indicates that soybean
      milk with chromium fortification can improve glucose and lipid metabolism of
      diabetic rat, and has a potential use in the diabetes mellitus prevention and
      control.

PMID- 14650198
TI  - [Quantitative analysis of resveratrol from grape seeds and grape skins by high
      performance liquid chromatography method].
AB  - In order to perform a quantitative analysis of resveratrol from grape seeds,
      grape skins and waste residue of grape winery, acetonitrile-water (26:74) was
      applied as the fluxion phase. The detective wave-length (lambda) was 303 nm.
      Colume temperature was 35 degrees C. The type of chrimato pattern colume was
      SupelcosiLTMLC-18 (250 mm x 4.6 mm, 5 microns). Results showed that the contents
      of resveratrol from grape skins were higher than those of grape seeds. Among
      different kinds of grape skins, resveratrol contents varied. The reserveratrol
      content of Suo Suo grape skin was the lowest (0.9850 microgram/g). Among the same
      kinds of grape skins from the same production area, the resveratrol content was
      highest in the skin of waste residue of grape winery followed by the fresh grape
      skin and the old grape skin ranked thirdly, and the differences of resveratrol
      contents were statistically significant.

PMID- 14650199
TI  - [Determination of tetramine in plasma by gas chromatography].
AB  - A method was developed to measure the tetramine in plasma by liquid-liquid
      extraction and GC-NPD with the limit of detection (LOD) 1.5 pg and the limit of
      quantity 10 ng/ml. The linear range was 0.1-5 micrograms/ml with a correlation
      coefficient of 0.999. Recoveries for three concentrations of tetramine were
      96.0%, 107.0%, 106.8%. The intra-day precision were 9.6%, 9.8%, 7.8%, the inter
      day precision were 6.6%, 8.5%, 6.2%. Tetramine in plasma was stable up to 5
      months at -4 degrees C.

PMID- 14650200
TI  - [Comparison of HemoCue with cyanmethemoglobin method for estimating hemoglobin].
AB  - Hemoglobin level was the most common factor used in evaluation the iron status
      and anemia prevalence in population. We used HemoCue method and cyanmethemoglobin
      method for estimating hemoglobin by capillary blood samples from 280 3-5 years
      old-children and vein blood samples from 71 12-13 years-old children, a serial of
      control blood samples were measured also. The results showed that the two methods
      had good corelationships in estimating hemoglobin. The results from HemoCue
      method were higher than the cyanmethemoglobin method by both the capillary blood
      samples and vein blood samples. The greatness were (18.4 +/- 6.1) g/L by
      capillary blood samples and (3.4 +/- 4.4) g/L by vein blood samples respectively.
      The results indicated that in research studies cyanmethemoglobin method should be
      the best selection. HemoCue method has been found to be easy in operation, less
      in training and portable size, it can be used in the filed work that the
      cyanmethemoglobin method was not available. But the results should be adjusted.

PMID- 14650201
TI  - [Progress on industrial ecological studies of dry-cleaning process].
AB  - The safety assurance of dry cleaning solvent and rational residue criteria of
      volatile hazardous organic compounds in clothes are vital to clean production and
      green service in dry cleaning industry. Therefore, the environmental behavior of
      the enterprises should be regulated and assurance to the human health and the
      environment through the combination of environmental technologies and economic
      instruments. Progress on industrial ecological studies of dry-cleaning process
      was reviewed and the protective strategies and approaches of environmental safety
      technologies to the sustainable development of dry cleaning were put forward in
      this paper.

PMID- 14650202
TI  - [Progresses on adverse health effects of automobile exhaust].
AB  - The progresses on the latest studies at home and abroad on adverse health effects
      of automobile exhaust were reviewed in this paper. Particulates and poisonous
      gases from automobile exhaust were considered to be harmful to respiratory
      system, immune system and reproductive system. It showed that increased
      prevalence of respiratory disease (e.g. chronic bronchitis and asthma), and
      decreased lung function, immunity were associated with automobile exhaust. The
      carcinogenic potential from the exposure to automobile exhausts needs to be
      further explored because the carcinogenesis is multifactorial.

PMID- 14650203
TI  - [Endothelium derived relaxing factor and its effect on vascular disease].
AB  - The finding of endothelium derived relaxing factor (EDRF) and the illumination of
      its chemical identity, bio-synthesis and physiological functions promoted greatly
      the research on vascular disease. The EDRF was verified as NO or R-O-NO by many
      experimental results, and several pathological processes such as hypertension,
      atherosclerosis and heart failure were considered to be associated with
      abnormalities of endothellium-dependent vascular relaxation and decrease of basal
      EDRF and/or storage EDRF. As the provider of EDRF, Nitryl vascular relaxation
      substance could remedy EDRF and might play an important role in clinical therapy
      and prevention of human vascular disease.

PMID- 14650204
TI  - [Effect of a new antiparkinsonian drug himantane on monoamine oxidase activity].
AB  - N-2(adamantyl)hexamethyleneimine hydrochloride (hemantane) is a new potential
      antiparkinsonian drug targeted at several neurochemical systems. The drug
      exhibits the properties of a low-affinity noncompetitive blocker of the ion
      channels of glutamate NMDA receptors. Hemantane increases the content of dopamine
      in the striatum, while decreasing the level of dopamine metabolite
      dioxyphenylacetic acid (DOPAC). Investigation of the drug interaction with
      monoamine oxidases (MAOs) of the A and B types in vitro showed that hemantane
      acts as a weak competitive inhibitor of MAO-B (Ki = 470 +/- 70 microM) and partly
      protected MAO-B from irreversible inhibition by selegiline (deprenyl), while
      virtually not influencing the activity of MAO-A. Administered to C57BL6 mice (20
      100 mg/kg), hemantane did not influence the activity of MAO-B measured in
      isolated cerebral mitochondria. At the same time, hemantane administered in
      combination with deprenyl significantly reduced activity of the latter drug and
      caused pronounced irreversible inhibition of mitochondrial MAO-B (comparable with
      the effect of deprenyl introduced alone). Therefore, inhibition of MAO-B may
      contribute to the spectrum of neurochemical activity of hemantane.

PMID- 14650205
TI  - [Effect of GABA on phosphoinositide cycle and membrane lipid modification in the
      brain synaptosomes of rats in hypokinesia].
AB  - The influence of a 30-day hypokinesia on the phosphoinositide cycle (PIC)
      initiation and on the inclusion of [14C]-arachidonic acid into cerebral
      synaptosome phospholipids was studied in rats. The results show that the
      catabolism of phospholipids prevails on the background of signal transduction in
      synaptosomes on the 30th day of hypokinesia. The effect of gamma-aminobutyric
      acid (GABA) is manifested by a sharp increase in the PIC activity 5 sec upon
      initiation and leads to normalization of the PIC activity in the late stage (5
      min).

PMID- 14650206
TI  - [Effect of eleutherococcus on short-term memory and visual perception in healthy
      humans].
AB  - Acute administration of a liquid eleutherococcus extract significantly improves
      short-term memory in healthy humans. The expression of this action depends on the
      daytime and psychophysiological peculiarities of the volunteers. Administration
      of the preparation also changes light perception by increasing retinal
      sensitivity. This effect was more pronounced in humans with weak type of high
      nervous activity in evening hours.

PMID- 14650207
TI  - [Effect of vinpocetine on cerebral circulation in rats after exposure to
      radiation].
AB  - Vinpocetine (5 mg/kg) increases the cerebral blood flow rate, retains
      autoregulation, and positively influences carbohydrate and transcapillary
      metabolism in rats upon single irradiation to a dose of 2 Gy.

PMID- 14650208
TI  - [Effect of energostim on myocardial damage during coronary artery occlusion].
AB  - In contrast to traditional therapy (beta-adrenoblocker and nitrates), energostim
      improves the systolic and diastolic functions of myocardium during 120-min
      occlusion of the left descending coronary artery. The energostim-induced
      improvement in the central hemodynamics is correlated with an adaptive increase
      in activity of the antioxidant system enzymes in response to the ischemic
      production of reactive oxygen species, which is evidence of the mobilization of
      reserves of the enzymatic link in the antioxidant defense system of
      cardiomyocytes. Analogous pattern is observed in the blood. In the control group
      of traditional therapy, a decrease in the superoxide dismutase (SOD) activity and
      the redox potential (NAD/NADH) in myocardium are correlated with a decrease in
      the maximum rate of pressure increase in the left ventricle (R 6.4, p < 0.01)
      observed 2 h after the coronary occlusion. In the energostim treated group, there
      is a correlation between the SOD activity and the content of cytochrome C in
      mitochondria (R 6.1, p < 0.01): a change in the level of cytochrome C during 2-h
      acute ischemia is correlated with the decrease in redox potential (NAD/NADH) and
      in the ratio of glutathione peroxidase to Mn-dependent SOD (r 0.64, p < 0.01).
      Thus, disturbances in the antioxidant defense system of both myocardium and blood
      plasma of the patients with acute myocardium infarction are correlated with
      inability of the energy supply system to utilize oxygen in the process of
      glycolysis and oxidative phosphorylation in mitochondria. Stable adaptive
      increase in activity of the antioxidant defense system enzymes and a decrease in
      the content of cytochrome C in the blood plasma are probably the independent
      indications of beneficial prognosis and high efficacy of the proposed treatment
      of the ischemic damage of myocardium.

PMID- 14650209
TI  - [Study of antiarrhythmic activity and duration of action of quaternidine].
AB  - The results of experiments on dogs showed that quaternidine, a quaternary
      ammonium derivative of trimecaine, produces a significant antiarrhythmogenic
      effect in cases of rhythm disorders in the late stage of a model myocardial
      infarction. For drugs administered in a single isotoxic dose, the therapeutic
      effect of quaternidine in animals with acute myocardial ischemia considerably
      exceeds the duration of action of lidocaine and trimecaine.

PMID- 14650210
TI  - [Effect of mexidol on efficacy of traditional therapy of sick sinus syndrome in
      adolescents].
AB  - ECG data obtained with a Holter monitor in a group of 90 adolescent patients with
      vegetovascular dystonia and sick sinus syndrome (SSS) showed that mexidol,
      intravenously instilled in a daily dose of 2-4 mg/kg over a period of 10 days in
      combination with a standard neurometabolic scheme results in the development of a
      therapeutic effect in 93-100% of patients with clinical-ECG variants I and II of
      the disorder. In most cases, both clinical state and ECG quality were improved
      and the functional capacity of myocardium was increased. Repeated courses of
      mexidol administration increased efficacy of the ambulatory SSS treatment on the
      average by 20%.

PMID- 14650211
TI  - [Anti-inflammatory activity of hyaluronic acid].
AB  - The results of in vivo experiments showed that hyaluronic acid possesses
      antiexudative activity comparable with that of nonsteroidal anti-inflammatory
      drugs. Hyaluronic acid exhibits antagonism with respect to histamine-induced
      inflammation.

PMID- 14650212
TI  - [Types of biochemical response to acute pharmacological indomethacin probe in
      healthy volunteers].
AB  - By the type of biochemical response to acute pharmacological indomethacin probe,
      a group of both male and female healthy volunteers can be subdivided into two
      parts. The first part includes volunteers with a stability index reduced as a
      result of accumulation of the oxidized products and a decrease in the content of
      reduced glutathione (GSH). The second part includes volunteers with the stability
      index increased as a result of decrease in the amount of lipid peroxidation
      products and an increase in the GSH content. A difference between males and
      females with respect to the response type consisted in that females features
      changes in the gutathione buffer components, and males, in the activity of
      antioxidant enzymes (catalase and peroxidase).

PMID- 14650213
TI  - [Use of alpha-tocopherol in correction of red blood (erythron) system disorders
      in rats with acute nitrite intoxication].
AB  - The erythron system response to acute nitrite intoxication and the possible
      antioxidant correction was studied in rats poisoned with sodium nitrite with and
      without pretreatment with alpha-tocopherol. The state of the experimental;
      animals was characterized by monitoring the peripheral blood parameters, the
      surface cytoarhitectonics and the hemolytic activity of erythrocytes, the level
      of methemoglobin and nitrate ions in the blood, and the cellular composition of
      hemopoietic organs, and the state of intracell erythrodiuresis. It is established
      that the acute intoxication with sodium nitrite leads to a hemolytic anemia
      accompanied by reactive ejection of reticulocytes from the red bone marrow,
      methemoglobinemia, leukocytolysis, and a decrease in the adhesive and phagocytic
      activity of macrophages. The preliminary administration of alpha-tocopherol leads
      to a less pronounced intravascular hemolysis of erythrocytes, which is explained
      by reactivation of the intracellular mechanisms of erythrocyte destruction and by
      retention of the population of circulating erythrocytes with satisfactory
      characteristics of the morphofunctional state of the cell membrane.

PMID- 14650214
TI  - [Study of pharmacological activity of complex magnesium-containing preparation
      based on mineral bishofit and pyridoxine hydrochloride in a rat model of chronic
      alcoholic intoxication].
AB  - Nervous disturbances accompanying alcoholic illness were studied in relation to
      the depletion of magnesium ion content in the organism. The possibility of
      correcting the development of psychic (behavioral) pathologies by treatment with
      a complex magnesium-containing preparation based on mineral bishofit and
      pyridoxine hydrochloride (below, Mg-containing preparation) was studied in rats
      upon three-month voluntary alcoholization. A decrease in the locomotor (number of
      crossed squares) and vertical (number of standings) activity as evaluated in the
      open-field test and an increase in the immobilization time in the forced swim
      test showed evidence of depressive state in animals after long-term ethanol
      administration. After treatment with the Mg-containing preparation (50 mg Mg/kg
      in 2.5 ml volume, p.o.), the immobilization time of alcohol-preferring rats
      decreased in comparison to that before treatment and showed no statistically
      significant differences from the value in the intact control group. A decrease in
      the immobilization time (the main sign of antidepressant action) allows the Mg
      containing preparation to be considered as antidepressant. The level of magnesium
      in rat blood erythrocytes decreased upon three-month voluntary alcoholization by
      40.95 +/- 2.41% relative to control (p < 0.05). After a 5-week treatment with Mg
      containing preparation under conditions of free access to alcohol, the content of
      magnesium in the erythrocytes of alcohol-preferring rats restored on a normal
      level. Chronic alcoholism reduces the content of microelements and vitamins (in
      particular, B6), these changes being mutually related.

PMID- 14650215
TI  - [Effect of acetylsalicylic and mefenamic acids on cytoarchitectonic of skin in
      rats with acute local cryogenic trauma].
AB  - The effect of acetylsalicylic (250 mg/kg) and mephenamic (50 mg/kg) acids on the
      process of skin cytoarchitectonics restoration was studied in rats with acute
      local cryogenic traumas induced by acting with a stream of ethyl chloride upon
      epilated back skin area (1.5 cm2). The animals were killed under narcosis on the
      12th day of post-treatment observation. Both acetylsalicylic and mephenamic acids
      were administered per os twice per day over various periods after cryogenic
      damage. The effect depended on the treatment duration. The normal skin
      cytoarchitectonics was restored by acetylsalicylic acid in half, and by
      mephenamic acid, in one-third of cases (for a "combined" administration scheme).

PMID- 14650216
TI  - [Effect of the bone cement on human fibroblast culture and possible ways of its
      correction by cytoprotector preparations].
AB  - The results of in vitro investigation are used to assess the effect of
      poly(methyl methacrylate) based bone cements (BCs) upon human fibroblast culture.
      The dose dependent cytotoxic effect of BCs (Polacris) was manifested by the
      development of oxidative stress and hypoxia (on the cell level) and by a decrease
      in the cell ability to multiplication. The drugs possessing antihypoxant
      (mafusol) and antioxidant (erysod) activity, introduced into the incubation
      medium in clinically adequate doses, significantly reduced the toxic effect of
      BCs. The maximum positive effect was observed upon a combined administration of
      both drugs.

PMID- 14650217
TI  - [Differences in prooxidant effect of neuroleptics haloperidol and aminazine].
AB  - In the in vitro experiments with hydrobiont Daphnia magna Straus as the test
      object the comparative evaluation of the prooxydant activity of two neuroleptics
      galoperidol and aminazine, was performed. It was shown that galoperidol possesses
      the pronounced prooxydant activity compared with hydrogen peroxyde. Aminazine
      didn't display such an action. The exogenios reduced glutathione is capable to
      protect Daphnia from the prooxydant action of galoperidol may be used for the
      investigation of anti- and prooxydant effects of toxicants and medicines in vivo.

PMID- 14650218
TI  - [Application of chemiluminescent analysis for comparative assessment of
      antioxidant activity of some pharmacological compounds].
AB  - A comparative analysis of the antioxidant activity of a series of pharmacological
      compounds was performed in vitro using Fe2+ induced chemiluminescence of
      lipoproteins. With respect to the protective action against lipoprotein
      oxidation, the compounds studied can be arranged in the following order: trolox >
      carnosine > emoxypine > L-carnitine = mildronate. The results show good prospects
      for using the proposed chemiluminescent technique for evaluating the antioxidant
      activity of pharmaceuticals.

PMID- 14650219
TI  - [Central effects of ORL1 receptor ligands].
AB  - It has been discussed literature data on molecular structure of ORL1 receptor and
      its interaction with intracellular signal systems and neurotransmitters. Data on
      chemical structure of ORL1 receptor ligands and their central effects
      (nociception, locomotion, feeding, cognition) are presented.

PMID- 14650220
TI  - [Agmatine--an endogenous ligand of imidazoline receptors].
AB  - The existence of imidazoline receptors was suggested based on the results of
      investigation of the central hypotensive action of the alpha 2-adrenoreceptor
      agonist clonidine containing imidazoline group in the molecule structure.
      Experiments on the rostral venterolateral medulla oblongata (RVLM) neurons in
      rats showed that not less that 36% of specific binding sites in this zone differ
      from adrenergic and recognize imidazoline derivatives. Agmatine has proved to be
      an endogenous ligand of such imidazoline receptors.

PMID- 14650221
TI  - Overview of proteomics.

PMID- 14650223
TI  - Two-dimensional gel electrophoresis: a fundamental tool for expression proteomics
      studies.

PMID- 14650222
TI  - Sample preparation for 2-D proteomic analysis.

PMID- 14650224
TI  - Applications of mass spectrometry in proteomics.

PMID- 14650225
TI  - Mass spectrometric approaches to quantitative proteomics.

PMID- 14650226
TI  - Practical bioinformatics for proteomics.
AB  - We used various bioinformatic tools to examine the unknown protein gi|12841975
      that was up-regulated in mouse diabetic kidneys. The data indicate that this
      unknown protein is, indeed, the PEBP. Motif scanning showed that this protein
      contains several kinase motifs, especially PKC that plays an important role in
      the pathogenesis of diabetic nephropathy [24, 25]. We therefore hypothesize that
      this protein (PEBP) has a potential functional role in PKC-dependent pathogenic
      pathways of diabetic nephropathy. Further study will be focused on
      phosphorylation pathways of the PEBP and its substrates. In summary, we have
      presented a case study that outlines our approach to further characterize the
      unknown proteins identified by peptide mass fingerprinting. Publicly accessible
      bioinformatic tools can provide a wealth of information to guide subsequent
      approaches that use traditional molecular biology tools.

PMID- 14650227
TI  - Clinical proteomics: application at the bedside.

PMID- 14650228
TI  - Proteomics and nephrotoxicity.

PMID- 14650229
TI  - Proteomics and sodium transport.

PMID- 14650230
TI  - Proteomics and diabetic nephropathy.

PMID- 14650231
TI  - Urinary proteomics of renal Fanconi syndrome.

PMID- 14650232
TI  - Application of mass spectrometry to IgA nephropathy: structural and biological
      analyses of underglycosylated IgA1 molecules.

PMID- 14650233
TI  - Podocyte proteomics.

PMID- 14650234
TI  - Proteomics and mesangial cell: serpin, megsin and plasmin.

PMID- 14650235
TI  - Proteomic analysis reveals novel protein targets of S-nitrosylation in mesangial
      cells.

PMID- 14650236
TI  - Proteomic approach to identification of novel kinase substrates in mesangial
      cells.

PMID- 14650237
TI  - Proteomics and hypertension.

PMID- 14650238
TI  - Proteomic studies in urological malignancies.

PMID- 14650239
TI  - A proteomic analysis of proteins removed by ultrafiltration during extracorporeal
      renal replacement therapy.

PMID- 14650241
TI  - Proteomics and drug discovery.

PMID- 14650240
TI  - Urinary proteomics and biomarker discovery for glomerular diseases.

PMID- 14650242
TI  - Central warehouses offer savings, security.

PMID- 14650243
TI  - Price survey. Paper demand set to rebound.

PMID- 14650244
TI  - Poll: supply chain often underestimated.

PMID- 14650245
TI  - M.D. Anderson report states mission as being #1 in cancer care. Named winner of
      new Founder's Award.
AB  - The Founder's Award was established this year specifically to recognize the
      University of Texas M.D. Anderson Cancer Center. A past winner in earlier Annual
      Awards competitions, the institution is to be admired for for its consistently
      outstanding efforts to communicate effectively with its community, its
      stakeholders and the medical community worldwide. Each year, the entries in
      Profiles' competition increase both in quantity and quality, making this year's
      selections the best ones yet.

PMID- 14650246
TI  - Department of surgery annual report celebrates leadership. University of
      Pennsylvania Health System report is strong recruiting, fund raising and
      communications tool.
AB  - The University of Pennsylvania Health System, Philadelphia, receives a Special
      Award for its Department of Surgery Annual report.

PMID- 14650247
TI  - Sun Health report to medical staff builds corporate culture. Attractive, quick
      read addresses physicians' issues.
AB  - Sun Health Report to Physicians, Sun City, Ariz., is recognized with a Special
      Award.

PMID- 14650248
TI  - CD-ROM assists Baystate Health System in sharing financial info.
AB  - Baystate Health System, Springfield, Mass., receives a special award for its
      unique use of a CD-ROM, which allows it to convey considerably more information.

PMID- 14650249
TI  - Tampa General's report is strong on fundraising.

PMID- 14650250
TI  - Cleveland Clinic demonstrates world class service.

PMID- 14650251
TI  - Dartmouth-Hitchcock promotes difference, elevates image.

PMID- 14650252
TI  - Winning entry is a standout. A magical journey for Cancer Center at Ball Memorial
      Hospital.
AB  - One report stands out in this highly diverse category. First place goes to the
      Cancer Center at Ball Memorial Hospital, Muncie, Ind.

PMID- 14650253
TI  - Community hospital focus: quality. Rush-Copley Medical Center a prime example.

PMID- 14650254
TI  - Concord, community hospitals, proud of community resource role.

PMID- 14650255
TI  - New CEO creates a new tone for Rome Memorial Hospital.

PMID- 14650256
TI  - Baptist Health puts focus on people, technology and growth. 'Depend on us for
      life' cleverly combines community, foundation reports in dual format.

PMID- 14650257
TI  - Sparrow's Family Album creates sense of longevity, continuity. Report highlights
      nurses, doctors and services in subtle ways.

PMID- 14650258
TI  - Memorial HC System creates image of success, quality in upscale report. Size,
      design, photos, layout, paper all convey clear impression.

PMID- 14650259
TI  - Change, community major themes. SwedishAmerican leads the pack as proponent of
      change.

PMID- 14650260
TI  - HealthONE asserts community partner role.

PMID- 14650261
TI  - Lutheran Medical Center shows how it supports its Brooklyn community.

PMID- 14650262
TI  - Two Iowa hospitals take awards. At Grinnell Regional, red ink makes for a winning
      report.

PMID- 14650263
TI  - Report from St. Anthony Regional makes every penny count.

PMID- 14650264
TI  - Children's needs shown to donors. Children's Healthcare of Atlanta previews
      capital campaign.
AB  - The standout in this category, taking First place, is Children's Healthcare of
      Atlanta, Atlanta, Ga.

PMID- 14650265
TI  - Ball Memorial pays artistic tribute to medicine as an art. BMH Foundation, Inc.
      report achieves goals through graphics.
AB  - The Foundation report from Ball Memorial Hospital, Muncie, Ind., is distinguished
      by its graphics.

PMID- 14650266
TI  - Robert Wood Johnson University Hospital, Amery Regional honored.
AB  - Robert Wood Johnson University Hospital, New Brunswick, N.J., is honored for a
      distinctive foundation report. Amery Regional Medical Center, Amery, Wis., also
      receives honorable mention for its outstanding report in the Community Hospital
      category.

PMID- 14650267
TI  - Looking for answers. Boards struggle to find the proper way to compensate
      executives.
AB  - Boards are facing tough choices on executive compensation: Does their
      compensation package reward the right things? Is it too high or too low? The 2003
      annual Hay Compensation Report gives boards the comparative data they need to
      help make the right choices.

PMID- 14650268
TI  - Succession planning. Dress rehearsal for the understudies.
AB  - Grooming internal talent for the number one slot in the organization not only
      eases the transition to new leadership, it's also good business savvy.

PMID- 14650269
TI  - Trustee workbook 4. What boards should know about turnarounds.

PMID- 14650270
TI  - Taking the prudent path. Best practices for not-for-profit boards.
AB  - A direct outgrowth of the Sarbanes-Oxley Act, best practices in corporate
      governance strengthen board independence, provide a framework for ethical
      decision-making and enhance compliance with state and national regulations.

PMID- 14650271
TI  - The Joint Commission in 2004: what the board needs to know.
AB  - Changes to Joint Commission standards for 2004 not only enhance their fairness
      and logic, but will improve care for currently hospitalized patients.

PMID- 14650272
TI  - The tale of two turnarounds: an exercise.

PMID- 14650273
TI  - Codes of ethics in the wake of Sarbanes-Oxley.

PMID- 14650274
TI  - Making effective dietary recommendations.

PMID- 14650275
TI  - Paid feeding assistants.

PMID- 14650276
TI  - CASAWORKS for Families. A new treatment model for substance-abusing parenting
      women on welfare.
AB  - This article provides a brief overview of CASAWORKS for Families (CWF), an
      innovative intervention designed to help substance-abusing parenting women on
      welfare. CWF was developed in response to the passage of welfare reform
      legislation in 1996. Factors that provided a background and context for the
      development of CWF are considered. The rationale, key elements, and the conduct
      of a pilot demonstration of CWF are described. Evaluation findings that serve to
      guide the next steps to improve the intervention are reviewed. Finally, new
      welfare policy priorities emerging around the importance of addressing behavioral
      health problems among welfare recipients are highlighted.

PMID- 14650277
TI  - Characteristics of substance-abusing women on welfare. Findings from the
      evaluation of CASAWORKS for Families pilot demonstration.
AB  - AIM: To describe and compare the characteristics and needs of substance-abusing
      women on Temporary Assistance to Needy Families (TANF) who enroll in a multi
      service "welfare to work" program (n = 673) with two other relevant groups: (a)
      women from the general TANF population in the same locales (n = 157) and (b) a
      sample of substance-abusing women on TANF who entered standard outpatient
      substance-abuse treatment programs (n = 520). DESIGN: A field study with repeated
      measures and intent-to-treat sampling. INTERVENTION: The CASAWORKS for Families
      (CWF) program was delivered in 11 sites in 9 states across the country. The CWF
      intervention featured integration of substance-abuse treatment and employment
      work readiness services, using case management to tailor needed services
      (parenting, victimization, mental health, physical health, legal, and basic
      needs). MEASUREMENT: The Addiction Severity Index, supplemented with subject
      appropriate questions, was used at treatment admission. FINDINGS: The CWF sample
      exhibited multiple serious problems in the areas of substance abuse,
      victimization, medical and psychiatric health, and basic needs. The severity of
      their lifetime problems and their recent service needs were significantly higher
      in all these areas, except physical health, than were those of the general
      welfare sample of women in the same locales. Compared with women on TANF from
      standard addiction-treatment programs, CWF women exhibited similar substance-use
      problems but generally more severe co-occurring problems.

PMID- 14650278
TI  - Treatment services received in the CASAWORKS for Families program.
AB  - This article presents information on treatment services received by women
      participating in an initial multistate evaluation of CASAWORKS families. Results
      indicated most women received services to address medical, employment, basic
      needs, alcohol and drug, family, and psychiatric problems during the first six
      months of the program. The clients also had frequent contact with their case
      managers and were retained in the program for an average of 222 days.
      Considerable variation was observed across sites in the percentage of clients who
      received various services and the number of sessions they received. In Cox
      regressions, shorter retention in the program was predicted by referral to
      program from Child Protective Services or parole/probation, social conflicts,
      employment, and marijuana use at baseline, whereas a history of suicide attempts
      was associated with longer retention. Longer retention was associated with better
      alcohol use outcomes but was unrelated to employment or drug use outcomes.

PMID- 14650279
TI  - One-year outcomes from the CASAWORKS for Families intervention for substance
      abusing women on welfare.
AB  - AIM: To evaluate the effectiveness of a multiservice intervention designed to
      move substance-abusing women on welfare to sobriety and self-sufficiency by
      addressing their substance abuse, domestic violence, employment, and basic needs.
      DESIGN: A field evaluation with repeated measures at 6 and 12 months on an intent
      to-treat sample of 529 women conducted in 11 selected sites across the country.
      There were significant improvements shown in substance use and family and social
      functioning by the 6-month point, and additional improvements in employment by
      the 12-month point. By 12 months, more than 46% were abstinent from alcohol and
      other drugs, and 30% were employed at least part-time. There were only modest
      improvements shown in the medical and psychiatric status of these women. These
      preliminary findings suggest that site-level interagency coordination and program
      level case management were associated with improvements in the targeted areas as
      predicted by the model. Future work will require a more closely specified, manual
      guided form of the intervention plus the inclusion of control groups and cost
      measures to fully evaluate the cost benefits from the final form of the
      intervention.

PMID- 14650280
TI  - Potential barriers to work for substance-abusing women on welfare. Findings from
      the CASAWORKS for Families pilot demonstration.
AB  - AIM: To assess the prevalence and relationship to later employment of potential
      barriers to work for substance-abusing women on Temporary Assistance to Needy
      Families (TANF) enrolled in a multiservice welfare-to-work program. DESIGN: A
      field study with repeated measures and intent-to-treat sampling. INTERVENTION:
      The CASAWORKS for Families (CWF) was delivered in 11 sites in nine states across
      the nation and featured integration of substance-abuse treatment and employment
      and work readiness services. MEASUREMENT: The Addiction Severity Index,
      supplemented with subject-appropriate questions. SAMPLE: A total of 366 CWF women
      who completed interviews at program enrollment, and at 6 and 12 months later.
      FINDINGS: Substance-abusing women on TANF in the CWF program exhibited multiple
      potential barriers to work at enrollment, averaging 6 out of 14 potential
      barriers assessed. They reported significantly more obstacles than a general
      welfare sample of women from the same locales. Few single barriers were
      significantly related to employment at 12 months. However, the total number of
      potential barriers to work experienced, particularly at 6 months, was related to
      employment at 12 months.

PMID- 14650281
TI  - [Upper urinary tract tumor: conservative treatment of localized forms].

PMID- 14650282
TI  - [Genetic cause of male infertility and molecular biology].
AB  - At the present time, 15% of couples experience reproduction difficulties.
      Surgical collection of spermatozoa associated with the intracytoplasmic sperm
      injection technique (ICSI) resolves the problems of male infertility formerly
      considered to be irreversible, regardless of its aetiology. Molecular biology now
      allows evaluation of the genetic dimension of male infertility. Although it
      demonstrates the multiple aetiologies of male infertility, it also reveals the
      gaps in our knowledge and the extent of the task that has yet to be accomplished.
      Microdeletion of the Y chromosome, detected in 2% to 20% of infertile patients
      with a disorder of spermatogenesis, has already been well documented. All of the
      genes involved on the Y chromosome (DAZ, RBMY, etc.) in infertile patients have
      been shown to be involved in spermatogenesis. Testing for other genes of the
      genome would also be useful. However, the unknown outcome of these abnormalities
      with successive generations raises a number of questions. In this article, the
      authors describe the main genes involved in spermatogenesis as demonstrated by
      molecular biology.

PMID- 14650283
TI  - [Does scrotal blunt trauma require surgical treatment?].
AB  - Blunt trauma to the scrotum is increasingly frequent and is mainly due to motor
      vehicle accidents, especially with direct trauma from a motorbike petrol tank or
      falling astride a bicycle frame. The surgical exploration of these cases of
      trauma remains a controversial issue. However, according to the authors, the
      presence of haematocele on clinical examination justifies systematic early
      surgical exploration, which shortens the patient's length of hospital stay
      allowing more rapid return to work. Ultrasound is only really indicated in the
      case of scrotal trauma without haematocele, looking for rupture of the tunica
      albuginea or intratesticular haematoma.

PMID- 14650284
TI  - [Extended total nephrectomy with laparoscopy in localized renal carcinoma. Report
      of 25 cases compared with 32 conventional surgical cases].
AB  - STUDY OBJECTIVE: To evaluate the benefits obtained during the learning phase of
      laparoscopic nephrectomy (LN) for clinical stage cT1 and cT2 renal cancers.
      PATIENTS AND METHODS: We retrospectively compared our first 25 cases of LN (13
      right, 12 left) with 32 nephrectomies performed by Conventional Surgery (CS) (17
      right, 15 left) between May 2000 and December 2001. The LN group comprised 18 men
      and 7 women with a mean age of 63.8 years. The CS group comprised 18 men and 14
      women with a mean age of 67.7 years. Preoperative, intraoperative, postoperative
      and histological parameters were compared by analysis of the variance or
      nonparametric Mann-Whitney U test for quantitative variables and Chi-square test
      for qualitative data. RESULTS: Preoperative and histological parameters, blood
      loss, quantity and duration of analgesics and the complication rate were similar
      in the two groups. Resection was complete in every case. The mean duration of
      radical nephrectomy was significantly shorter by CS (p < 0.001). Return of bowel
      sounds was more rapid (p = 0.002) and patients were discharged from hospital
      earlier (p = 0.004) after LN. CONCLUSION: Laparoscopic nephrectomy for cancer
      must be performed by an operator experienced in laparoscopy. During the learning
      phase, this procedure provided benefits in terms of return of bowel sounds and
      length of hospital stay, which should encourage teams performing laparoscopy to
      perform radical nephrectomy by laparoscopy.

PMID- 14650285
TI  - [Simple nephrectomy with retroperitoneal laparoscopy].
AB  - OBJECTIVE: Nephrectomy was one of the very first urological procedures to be
      performed by laparoscopy. The objective of this study was to evaluate the results
      of retroperitoneal laparoscopic simple nephrectomy. METHODS: From 1995 to 2002,
      88 retroperitoneal laparoscopic simple nephrectomies were performed in 87
      patients with a mean age of 45.3 years (range: 18 to 77 years). The
      intraoperative and postoperative complications, conversion rate, blood loss,
      operating time and length of hospital stay were studied for each patient.
      RESULTS: The mean operating time was 114 min (range: 35 to 280 min), mean blood
      loss was 97.6 ml (range: 0 to 300 ml), there were 3 conversions (3.4%) and the
      mean length of hospital stay was 4.7 days (range: 2 to 13 days). The main
      postoperative complications were 2 cases of haematoma and one abscess of the
      nephrectomy site requiring surgical revision and 3 intraoperative thromboses of
      arteriovenous fistulas in 3 patients with polycystic kidney disease. CONCLUSION:
      Due to its low morbidity, laparoscopic simple nephrectomy has probably become
      the, reference technique for all indications for nephrectomy for benign disease.

PMID- 14650286
TI  - [Sensitivity of abdominal radiography without preparation compared with computed
      tomography in the assessment of residual fragments after percutaneous
      nephrolithotomy].
AB  - INTRODUCTION: Evaluation of possible residual fragments after percutaneous
      nephrolithotomy is an essential aspect of the management of stone disease. The
      results of this evaluation determine the therapeutic approach, follow-up and
      presumed duration of treatment. The imaging modalities most frequently used are
      non-enhanced spiral computed tomography and plain abdominal x-ray. The objective
      of this study was to evaluate the contribution of spiral CT to the immediate
      follow-up of percutaneous nephrolithotomy. MATERIAL AND METHODS: Over a period of
      two years, we prospectively included 50 patients in whom plain abdominal x-ray
      and spiral CT were performed on the first postoperative day after percutaneous
      nephrolithotomy. The diagnosis of residual fragments was based on these
      examinations by 2 independent radiologists. RESULTS: The sensitivity for the
      detection of residual fragments was 87% for plain abdominal x-ray compared 100%
      for computed tomography. 89% of the fragments not diagnosed by plain abdominal x
      ray were less than 5 min. CONCLUSION: Plain abdominal x-ray was insufficient for
      the diagnosis of small residual fragments. Spiral CT is justified to confirm the
      absence of residual fragments in a patient after percutaneous nephrolithotomy
      despite the higher cost and irradiation compared to plain abdominal x-ray.

PMID- 14650287
TI  - [Value of preserved saphenous vein graft for the creation of access ports in
      hemodialyzed patients: report of 309 cases].
AB  - INTRODUCTION: Biological grafts are rarely used for the creation of vascular
      access, despite their many advantages. Our group prefers to use distal vascular
      accesses with interposition of a biological graft when direct access cannot be
      achieved. The objective of this study was to determine the long-term patency and
      the complication rate of a series of 309 vascular access procedures using a
      preserved saphenous (PS) vein homograft. MATERIALS AND METHODS: 410 (27%) of the
      1,500 vascular access procedures performed by our group required the use of a
      graft, including 376 PS vein homografts (25%). This retrospective study comprised
      complete data collection for 309 arteriovenous fistulas (AVF) using preserved
      saphenous (PS) vein graft in the forearm performed in 267 patients between 1985
      and 2000. Primary patency was defined as the interval between creation of the
      vascular access and the first complication requiring surgical or radiological
      correction; secondary patency was defined as the interval between creation and
      loss of the graft, with or without revision of the fistula. Survival rates were
      calculated according to the Kaplan-Meier method. Inter-group comparison was
      performed by the Logrank test and analysis of variance was performed by logistic
      regression. RESULTS: Primary patency rates were 77%, 40% and 27% at 1,2 and 5
      years, respectively. Secondary patency rates were 79% and 47% at 1 year and 5
      years, respectively. The thrombosis rate was 42%. Two episodes of thrombosis
      occurred in 25% of grafts and 3 episodes were observed in 10% of cases. Infection
      rates were 1.9% postoperatively and 5% after dialysis, respectively. An aneurysm
      occurred on 10% of grafts. The operator's experience (RR = 1.58; p < 0.05) and
      diabetic nephropathy (RR = 1.89; p = 0.059) significantly influenced graft
      patency. In contrast, the position of the graft, the fact that it crossed the
      elbow joint, and the site of the arterial anastomosis did not have any negative
      impact on graft patency. DISCUSSION: Preservation of the patient's vascular
      capital is an essential objective in patients with chronic renal insufficiency,
      which is sometimes difficult to reconcile with the need to create vascular
      accesses with a long life span. The strategic choice between a distal access
      requiring a graft and a direct proximal access depends on the clinical context:
      cardiac function, waiting list for renal transplantation. Our preferred material
      in the case of bypass graft is the PS graft, as it presents the same resistance
      and the same patency rates as synthetic grafts, without the associated septic
      complications. CONCLUSION: The PS vein graft is a good material for the creation
      of vascular accesses with similar patency rates to those of prosthetic grafts.
      Vein grafts present a number of advantages, particularly a greater ease of use
      facilitating distal implantation of the graft and a low infection rate.

PMID- 14650288
TI  - [Flexible double active deflection ureterorenoscopy].
AB  - INTRODUCTION AND OBJECTIVE: Secondary deflection of a flexible ureterorenoscope
      (FUR) is a passive mechanism, which can only be performed under certain
      anatomical conditions. The objective of this study was to present a new double
      active deflection FUR and to assess its value based on our initial experience.
      MATERIAL AND METHODS: From October 2002 to February 2003, we performed flexible
      retrograde ureterorenoscopy in 30 consecutive patients (34 renal units) using a
      double active deflection FUR (ACMI DUR 8 Elite). Bilateral ureterorenoscopy was
      performed during the same operating time in four patients. Ureterorenoscopy was
      diagnostic for 9 patients (macroscopic haematuria, urinary tract tumour), and
      therapeutic for 21 patients (stones, urinary tract tumour, ureteropelvic junction
      stenosis with stone). The value of double deflection as well as the efficacy and
      morbidity of the technique were evaluated. RESULTS: The main indication for
      flexible ureterorenoscopy was the treatment of urinary stones (73.6%), followed
      by the diagnosis of macroscopic haematuria and urinary tract tumours (26.4%).
      Ureteric dilatation was necessary in 38.3% of cases. The use of active secondary
      deflection was essential in 20% of cases (7/34) for complete investigation of the
      pyelocaliceal cavities. Access to the lower calices was not possible in one
      patient with a left pelvic kidney. 19 patients with urinary stones had no
      fragments (79.2%) at the end of the operation, while 4 had residual fragments in
      the lower calices. The global success rate for all operations was 85% (29/34).
      Two patients developed acute pyelonephritis during the 48 hours after the
      procedure and another two patients experienced acute renal colic. CONCLUSIONS:
      Our study confirms the data of the literature on flexible ureterorenoscopy in
      terms of indications and efficacy. The URS DUR 8 Elite allowed complete
      exploration of the pyelocaliceal cavities in more than 97% of cases. The use of
      active secondary deflection was unnecessary for the majority of patients (80%),
      but it represents a major technical progress which should be taken into account
      in the design of future flexible ureterorenoscopes.

PMID- 14650289
TI  - [Symptomatic vesicoureteral reflux in kidney transplantation: results of
      endoscopic injections of teflon and predictive factors for success].
AB  - OBJECTIVES: Evaluation of the results of endoscopic Teflon injections for the
      treatment of symptomatic vesicoureteric reflux in renal transplant recipients and
      identification of prognostic factors. POPULATION AND METHODS: Between June 1997
      and January 2002, out of a series of 408 renal transplant recipients, 15 patients
      (8 males, 7 females) with a mean age of 41.9 years were treated for symptomatic
      vesicoureteric reflux on the transplanted kidney by endoscopic Teflon injection.
      This treatment was indicated due to the presence of febrile or afebrile
      infections, possibly associated with deterioration of renal function. Reflux was
      demonstrated by retrograde cystography. The results of endoscopic treatment were
      evaluated by cystography at 3 months, and by clinical and laboratory examinations
      thereafter. RESULTS: The mean interval between renal transplantation and
      endoscopic treatment was 64.2 +/- 64.7 months. With a mean follow-up of 25 +/-
      16.7 months, we observed a 53.3% success rate (8 patients), 13.3% of patients (2
      patients) were improved and 33.3% of procedures were considered to be failures (5
      patients). A lower number of preoperative infections, reflux < or = grade III and
      the absence of impaired renal function are predictive factors for the success of
      endoscopic treatment. The only complication was one case of renal colic due to
      meatal stenosis at 3 months, which responded favourably to endoscopic treatment
      alone. CONCLUSION: Endoscopic treatment of symptomatic vesicoureteric reflux on a
      transplanted kidney by Teflon injection is effective in two-thirds of cases. Due
      to the low morbidity of this minimally invasive procedure, this treatment should
      be proposed as first-line management for all cases of symptomatic vesicoureteric
      reflux on a transplanted kidney.

PMID- 14650290
TI  - [Incidence of bladder cancer in France: trends from 1980 to 2000].
AB  - OBJECTIVE: This study was designed to provide up-dated incidence figures for
      bladder cancer in France. MATERIAL AND METHOD: The method used was based on
      modelling of the mortality/incidence ratio observed in French departments with
      cancer registries. RESULTS: The number of invasive cancers, which represent an
      average of slightly less than two-thirds of all bladder tumours diagnosed in
      France, increased in males from 5,591 in 1990 to 7,203 in 1990 and 8,986 in 2000.
      For females, these figures were 1,593, 1,744 and 1,787, respectively. This
      increase was mainly due to growth of the population, as incidence rates varied
      only slightly (+1.14% per year in males and -0.5% in females). Over the same
      period, the risk of death from bladder cancer decreased for both sexes.
      CONCLUSION: The diversity of the classifications, which clearly reflects the
      difficulty of defining bladder tumours, raises problems for descriptive
      epidemiology. This situation will probably be clarified by the consensus reached
      by pathologists over recent years.

PMID- 14650291
TI  - [Superficial grade G2 tumors of the bladder: recurrence, progression, prognosis].
AB  - OBJECTIVE: The primary objective of this study was to describe the course of a
      series of grade 2 noninvasive urothelial carcinomas and to determine their
      prognosis by establishing recurrence, progression and mortality rates The initial
      histological and endoscopic characteristics were analysed in order to identify
      risk factors for recurrence and progression towards detrusor invasion. MATERIAL
      AND METHODS: This retrospective study was conducted on 75 patients with initially
      grade 2 superficial bladder tumours. Tumours were initially multifocal in 47% of
      cases and were classified as follows: 52 pTa tumours (69%) and 23 pT1 tumours
      (31%). The mean follow-up was 58 months. RESULTS: After the initial endoscopic
      resection, 26 patients (3.9%) received adjuvant therapy by intravesical
      instillations. The overall recurrence and progression rates in this series were
      67% and 7%, respectively. Twelve patients (16%) underwent cystectomy. The
      specific mortality rate was 2.6%. Among the initial prognostic criteria, only the
      multifocal nature was identified as a risk factor for recurrence and progression
      towards detrusor invasion. CONCLUSION: This study confirmed the uncertain
      prognosis of grade 2 superficial bladder tumours. These tumours have a high
      recurrence risk with a cystectomy rate of 16%. These tumours require surveillance
      identical to that of high-grade tumours, at least half-yearly for the first 3
      years then annually thereafter.

PMID- 14650292
TI  - [Bladder nephrogenic metaplasia: circumstances of discovery, predisposing
      factors, and clinical course in 7 cases diagnosed between 1988 and 2000].
AB  - INTRODUCTION: Nephrogenic adenoma (NA) or nephrogenic metaplasia is a rare,
      benign urothelial tumour. MATERIAL AND METHODS: This retrospective study
      evaluated the circumstances of discovery, predisposing factors, and clinical
      course of seven patients with nephrogenic adenoma diagnosed between 1988 and
      2000. The mean age of these patients was 55.7 years (range: 16 to 88 years). The
      mean follow-up was 24 months (range: 4 to 108 months). RESULTS: There are no
      specific endoscopic findings and the lesion was sometimes flat or papillary with
      an appearance that can be identical to that of bladder tumour. The diagnosis was
      always based on histological findings. Suggestive clinical signs were nonspecific
      and comprised: haematuria, dysuria, or urgency. Treatment was surgical with
      transurethral resection or electrocoagulation of the lesion, combined with
      elimination of the factors irritating the urothelial mucosa. In our experience,
      recurrences were observed in 28.5% of patients and occurred during the year
      following the initial treatment. CONCLUSION: Nephrogenic adenoma is a rare,
      benign urothelial tumour most frequently situated in the bladder. The presenting
      clinical signs are completely nonspecific and usually related to predisposing
      factors (infections, inflammation, bladder tumour). Only histological examination
      can provide the essential proof of the benign nature of this lesion. Endoscopic
      resection therefore has two objectives: diagnostic and therapeutic. The clinical
      course is characterized by recurrences.

PMID- 14650293
TI  - [Cost and efficacy of treatment strategies in localized prostatic cancer:
      feasibility study in the general population].
AB  - OBJECTIVE: Medico-economic studies are necessary to evaluate healthcare
      practices. The objective of this preliminary study is to show how this type of
      study can be conducted in the general population based on cancer registries.
      MATERIAL AND METHODS: 122 cases of localized prostate cancer diagnosed in 1995 in
      the Tarn department were included in this study. A decisional tree of the main
      diagnostic strategies was elaborated. Direct medical and non-medical costs were
      considered from the payer's point of view and the 5-year survival was calculated.
      RESULTS: The costs of therapeutic management for radical prostatectomy, localized
      radiotherapy, endocrine therapy and watchful waiting were 55,468, 65,486, 72,211,
      and 13,929 French francs (8,533, 10,075, 11,109 and 2,143 euros) respectively.
      The observed 5-year survival was 89%, 84%, 75% and 79% respectively. CONCLUSION:
      This method can be applied to the CCAFU/FRANCIM cohort derived from 5 departments
      allowing comparisons between regions and healthcare sectors. The time-course
      could be determined by follow-up of a cohort of cancers diagnosed in 2001.

PMID- 14650294
TI  - [How to present in a unique fashion the oncologic and functional results after
      radical prostatectomy].
AB  - INTRODUCTION: The results of radical prostatectomy (cancer control, continence
      and sexual potency) are currently presented separately, while the success of this
      surgery depends on a combination of good cancer control with maintenance of
      continence and erections. We propose a score to jointly evaluate and report
      cancer control and functional results. METHODS: The results of 205 radical
      prostatectomies were studied at one year. Cancer control was evaluated by PSA and
      continence and sexual potency were evaluated by a self-administered
      questionnaire. Each patient was attributed 0 or 4 points according to the
      presence or absence of biochemical progression (PSA > 0.2 ng/ml), 0 or 2 points
      according to the presence or absence of urinary incontinence (use of pads) and 0
      or 1 point according to the presence or absence of impotence (no erections). The
      sum of these points provided a socre classifying the patient into 8 distinct
      categories, from 0 to 7, each corresponding to a specific status (from 0 (0 + 0 +
      0): no cancer control-incontinence-impotence to 7 (4 + 2 + 1): cancer control
      continence-sexual potency). RESULTS: One year after the operation, 175 (85%) of
      patients had a PSA less than 0.2 ng/ml, 135 (65.8%) were continent and 64 (32.7%)
      reported erections. All patients with a score > or = 4 had good cancer control,
      wit no functional disorders for a score of 7 (4 + 2 + 1) (92%), no disorders of
      continence for a score of 6 (4 + 2 + 1) (31.5%), no disorders of erection for a
      score of 5 (4 + 0 + 1) (8.3%), or with incontinence and impotence for a score of
      4 (4 + 0 + 0) (21.9%). All patients with a score < 4 had a PSA > 0.2 ng/ml, but
      with no functional disorders for a score for 3 (0 + 2 + 1) (2.4%), no
      incontinence for a score of 2 (0 + 2 + 0) (8.3%), and no impotence for a score of
      1 (0 + 0 + 1) (1.9%). 1.9% of patients were incontinent, impotent and showed
      signs of biochemical progression (socre 0 = 0 + 0 + 0). CONCLUSION: This score
      allows analysis of the global (cancer control and functional) results of radical
      prostatectomy and would facilitate comparisons between various surgical
      techniques (type of approach, nerve-sparing techniques) and various centres.

PMID- 14650295
TI  - [Organization and innervation of striated muscle fibers of the striated sphincter
      in the rat].
AB  - OBJECTIVES: To determine the organization of striated muscle fibre (FMS) of the
      rat striated sphincter (SS) and to characterize the motor endplates (MEP).
      MATERIAL AND METHODS: The urethras of 30 male and female rats were studied. Two
      thousand hematein-eosin stained serial sections and 800 sections simultaneously
      stained for MEPs and nerve endings were studied. RESULTS: The SMFs of the SS are
      organized in the urethral wall in four symmetrical bands. MEPs are predominantly
      found in the cranial third of the SS (22 MEPs per section). Sixty sixteen per
      cent of MEPs were situated in the lateral regions. Motor units were composed of a
      maximum of five SMFs. CONCLUSION: The SMFs of the SS are organized in four
      symmetrical bands. Myoconnective insertions of SMFs emphasize the importance of
      the connective tissue in their contractile action. They are innervated by a
      single MEP, in the same way as skeletal striated muscle fibres. In the SS, MEPs
      are predominantly located laterally to the right and to the left. The specific
      organization of motor units suggests an original mechanism of reinforcement of
      muscle contraction of the SS.

PMID- 14650296
TI  - [Synthetic suburethral sling in the treatment of stress urinary incontinence in
      women].
AB  - Since the marketing and success of the TVT technique, other products have been
      released onto the suburethral sling market. These products can be classified
      according to four main criteria: TAPE: The material used in every case is
      polypropylene, in the form of woven monofilaments (TVT, Sparc, Monarc, Uretex
      Sup), multi-filaments (IVS, Safyre comprising two silicone tension bands),
      extruded crosslinked polypropylene (Obtape) or silicone-coated polypropylene in
      contact with the urethra (Uratape). A larger space between the fibres is
      associated with a lower theoretical risk of infection and better tissue ingrowth.
      The weaving process of Uretex Sap tape decreases the warping and release effect.
      Extruded polypropylene forms a very solid, but poorly elastic tape. It is not yet
      clear whether silicone-coating is an advantage or a disadvantage. INCISION: The
      ascending retropubic approach (TVT, Uretex Sup, IVS) is now well known. It
      carries a risk of bladder perforation and, more exceptionally, intestinal or
      vascular injuries. The descending retropubic approach (Uretex Sup, Sparc)
      requires more extensive vaginal dissection and carries a risk of bladder
      perforation. The mixed retropubic approach (Uretex Sup) combines the potential
      disadvantages of the ascending and descending approaches. The transobturator
      approach (Uratape, Obtape, Monarc) was described more recently and is easy to
      learn. It does not carry any risk of intestinal or vascular injury, but the
      urethra, vagina or even the bladder (in the case of lateral cystocele) can be
      damaged by this incision. INSTRUMENTS: Ease of use is an essential feature.
      Uretex Sup comprises ancillary instruments and a technique requiring multiple
      manipulations. Sparc tape cannot be easily dissociated from the ancillary
      instruments when a second passage is necessary. TVT and Uratape use
      resterilizable instruments, while the other products are totally disposable.
      FOLLOW-UP AND PUBLICATIONS: Only TVT has a sufficient follow-up and several
      hundred specific papers or publications. Only a few publications by a few
      different teams are currently available for the other products. In conclusion,
      the various published studies confirm the qualities and good tolerance of woven
      monofilament polypropylene. The other materials require a longer follow-up and
      more studies before they can be completely validated in terms of results and
      morbidity. The multiple surgical approaches and the various ancillary instruments
      available allow the technique to be adapted to each patient and each surgeon,
      regardless of his or her initial training and habits.

PMID- 14650297
TI  - [Per- and postoperative complications of TVT (tension-free vaginal tape)].
AB  - OBJECTIVES: Data concerning the complications of TVT are rare, incomplete and
      discordant. We therefore decided to record all intraoperative and postoperative
      complications of TVT observed in our experience and to evaluate these
      complications as a function of the patients and operators. MATERIAL AND METHOD:
      This was a single-centre retrospective study of 157 patients with a mean follow
      up of 24 months (range: 5 to 50 months). We performed TVT either alone (76%) or
      associated with another pelvic surgical procedure (24%), especially simple
      vaginal hysterectomy (10%), and surgical repair of prolapse (14%). Some TVTs were
      performed in the presence of sphincter incompetence (32%) or mixed urinary
      incontinence (7%). The patient's history of pelvic surgery, vaginal surgery
      associated with TVT, the operator's experience, and the type of anaesthesia
      performed were assessed as risk factors for complications of TVT. RESULTS: The
      following complications were observed: bladder perforation (4.5%), urethral
      injury (0.6%), haemorrhagic dissection (5%), pelvic haematoma (0.6%), obturator
      nerve lesion (0.6%), suprapubic abscess (2%), urinary tract infection (7%),
      complete and lasting urinary retention (4%), expulsion of the TVT (2%), migration
      of the TVT (0.6%), de novo detrusor instability (1.5%). TVT was ineffective in 3%
      of patients. CONCLUSION: Although a global TVT complication rate of 28.4% in our
      series may seem high, it should be noted that these complications have a limited
      morbidity and usually have no consequences. Bladder perforation, haemorrhagic
      dissection, and urinary retention are the complications most frequently reported
      (4% to 5%). In this series, a history of pelvic surgery, an associated vaginal
      surgical procedure, and the operator's experience did not constitute risk factors
      for complication except in the case of haemorrhagic dissections; a history of
      pelvic surgery appeared to be a risk factor for intraoperative bleeding. In our
      experience, it is difficult to evaluate whether or not the type of anaesthesia
      performed for TVT increases the complication rate.

PMID- 14650298
TI  - [Transobturator tape (Uratape). A new minimally invasive method in the treatment
      of urinary incontinence in women].
AB  - OBJECTIVE: To evaluate the one-year results of transobturator suburethral tape
      for the treatment of female stress urinary incontinence. MATERIAL AND METHODS:
      Suburethral tape was implanted via the transobturator technique. UraTape non
      woven, non-elastic polypropylene tape with a 15 mm wide central (suburethral)
      silicone-coated zone was inserted without tension in a horizontal plane
      underneath the middle of the urethra from one obturator foramen to the other. The
      lateral ends of the tape were tunnelled percutaneously with a tunnelling device.
      The retropubic space was preserved and cystoscopy was not required. From May 2000
      to February 2002, 32 patients with a mean age of 64 years (range: 50 to 81
      years), suffering from stress urinary incontinence without associated prolapse,
      were operated by the same surgeon (ED). All patients were evaluated before the
      operation by clinical and urodynamic examination: 5 patients presented sphincter
      incompetence (maximum closing pressure < 20 cmH2O); five patients presented
      recurrent urinary incontinence after Burch or TVT; 18 patients presented mixed
      incontinence and detrusor instability was demonstrated on cystometry in 6 of
      them. The results were evaluated by two independent doctors (clinical
      examination, uroflowmetry, cough test). Voiding disorders suggestive of bladder
      outflow obstruction were defined by the presence of the following two criteria:
      Qmax < 15 ml/s, residual volume > 20%. RESULTS: The mean follow-up of the study
      was 17 months (range: 13 to 29 months). The mean operating time was 15 minutes.
      No intraoperative complication was observed. One patient presented complete
      postoperative bladder retention that resolved after 4 weeks of self
      catheterization. 29/32 patients (90.6%) were cured and 3/32 (9.4%) were improved.
      No urethral erosions were observed. No residual pain and no functional impairment
      related to the tape was observed. 5/32 patients presented voiding disorders
      suggestive of bladder outflow obstruction. Two patients developed de novo urge
      incontinence. CONCLUSIONS: Transobturator Uratape is a simple and effective
      procedure with a follow-up of one year for the treatment of female stress urinary
      incontinence. The transobturator approach avoids the risks of bladder, intestinal
      and vascular injuries. Evaluation of the results with a longer follow-up is
      necessary to validate this technique.

PMID- 14650299
TI  - [Original dorsal plasty of the glans in distal hypospadias].
AB  - The long-term follow-up of patients operated for hypospadias often reveals
      progressive recession of the neo-meatus, even when it is initially correctly
      situated. MATERIAL AND METHOD: To overcome this disadvantage, we decided to
      prolong the glanular groove by longitudinally incising the distal quarter of the
      dorsal surface of the glans. Transverse suture then defines the margins of the
      neo-meatus, creates or deepens the glanular groove and promotes the formation of
      a thick anterior wall which deeply covers a short triangular Mathieu flap. The
      foreskin is systematically reconstructed. Bladder drainage is ensured by an
      urethral stent attached to the glans for 7 days. Treatment can now be performed
      as an outpatient procedure. From 1992 to June 2002, 374 children, with a mean age
      of 25 months (range: 10 to 129 months) were treated by this technique, with
      foreskin reconstruction in 307 cases. The preoperative position of the meatus was
      posterior glanular in 31 cases (83%), peno-glanular in 191 cases (52%) and
      anterior penile in 152 cases (40.7%). RESULTS: All patients were reviewed with a
      mean follow-up of 19 months (range: 1 to 123 months). The position of the meatus
      was normal apical in 309 cases (82.6%): glanular: middle: 41 cases (11%);
      posterior: 14 cases (17%), peno-glanular: 1 case, dorsal: 6 cases (1.6%), not
      specified: 3 cases (tight phimosis). COMPLICATIONS: 25 fistulas (6.7%), 4
      stenoses (1.1%). DISCUSSION: The usual glanular urethroplasty, by simple suture
      of the margins, often results in a large meatus situated in the middle of the
      glans. When the meatus is placed below the glans, recession can lead to an
      anterior penile meatus. Dorsal glanuloplasty, by elongating and deepening the
      glanular groove, while preserving the urethral plate, allows the construction of
      a solid wall around the neourethra, reducing the risks of recession and
      enlargement of the meatus which retains a split-like appearance and ensures a
      good stream. Systematic foreskin reconstruction probably also plays a role in the
      quality of healing. CONCLUSION: This dorsal glanuloplasty, which corrects the
      penis and urinary stream in more than 80% of cases without any major
      disadvantages, is a useful technique in hypospadias repair.

PMID- 14650300
TI  - [Cystic dysplasia of the testis].
AB  - Cystic dysplasia of the testis is an exceptional benign tumour resulting from a
      functional abnormality of the connection between the rete testis and the efferent
      ductules of the epididymis. The authors report a new case observed in a child.
      The frequent association with a renal abnormality is highly suggestive. Treatment
      usually consists of orchidectomy, but can be conservative with long-term
      surveillance. The prognosis is usually excellent.

PMID- 14650301
TI  - [Inferior polar nephrectomy for multi-recurrent inferior caliceal cystine
      lithiasis].
AB  - The authors report a case of left inferior caliceal cystine stones, which
      recurred despite well conducted medical treatment, 12 extracorporeal lithotripsy
      sessions, and percutaneous nephrolithotomy. A left lower pole nephrectomy was
      finally performed. No recurrence on the left side was observed with a follow-up
      of 3 years. However, the patient developed two recurrences of the right side.

PMID- 14650302
TI  - [Partial infarction of the kidney caused by spontaneous idiopathic dissection of
      the renal artery].
AB  - Idiopathic spontaneous renal artery dissection (SRAD) is a rare disease and must
      be taken into account in the differential diagnosis of low back pain. It may be
      due to various aetiologies, secondary to degenerative or traumatic diseases, or
      it may be idiopathic. Intravenous urography is usually normal. Abdominal CT
      usually visualizes the renal infarction and selective arteriography confirms the
      diagnosis of renal artery dissection. Medical treatment and surveillance provide
      effective management of the disease. However, surgical management may be proposed
      either immediately or secondarily. SRAD usually has a favourable course, but, in
      the longer term, may be complicated by organic renal failure and renovascular
      hypertension.

PMID- 14650303
TI  - [Calculous renal failure and pregnancy].
AB  - Obstructive renal failure is a rare but serious complication of pregnancy.
      Although most cases are due to extrinsic compression, renal tract obstruction can
      also be due to intraluminal precipitation of sulfadiazine prescribed for
      maternofoetal toxoplasmosis. The diagnosis is suggested by clinical history,
      ultrasound (radiolucent stones situated anywhere in the renal tract) and
      especially analysis of the urine pellet (wheat sheaf formation of yellowish
      crystals). Urinary drainage by double J stent or percutaneous nephrotomy is
      indicated in the absence of clinical improvement in response to symptomatic
      treatment and adequate alkaline rehydration. The risk of sulfadiazine
      crystallization must be systematically prevented by a sufficient water intake and
      urinary alkalinization right from the start of treatment.

PMID- 14650304
TI  - [Torsion of the renal pedicle after kidney luxation after simultaneous double
      kidney and pancreas transplantation].
AB  - Torsion of a renal transplant around its pedicle is a rare complication, which
      has been described in renal transplant children with Prune Belly syndrome, but
      also exceptionally in adults undergoing kidney-pancreas transplantation. One of
      the diagnostic difficulties is due to the lack of specificity of the clinical
      features in some cases, which may lead to delayed diagnosis and loss of the
      kidney due to renal pedicle thrombosis. The authors report a case of a 31-year
      old woman undergoing simultaneously kidney-pancreas transplantation, who
      developed torsion of the renal pedicle following intraperitoneal rotation of the
      renal transplant several months after transplantation. They discuss the diagnosis
      and prevention of this exceptional complication.

PMID- 14650305
TI  - [Primary pleomorphic rhabdomyosarcoma of the kidney in adults: unusual tumor].
AB  - Primary rhabdomyosarcoma (RMS) of the kidney in an adult is a very rare and
      unusual tumor in this site. The clinical signs associated with the flank tumoral
      syndrome, the histologic appearance of cytoplasmic double striation in
      rhabdomyoblasts and the immunohistochemical expression of skeletal muscle
      differentiation (desmin, myoglobin, myogenin) are described in the context of a
      rapidly evolving renal RMS in a 77-year old man. The differential diagnosis are
      mainly represented by sarcomatoid renal cell carcinoma. According to the
      neoplastic extent, the treatment includes radical nephrectomy, chemotherapy and
      surgery. The prognosis of primary renal RMS is extremely poor, with lymph node,
      hepatic, bone marrow and pulmonary metastasis and a short survival rate.

PMID- 14650306
TI  - [Hemorrhagic bilateral renal angiomyolipoma].
AB  - Renal angiomyolipoma is a rare benign tumour, often associated with congenital
      diseases especially de Bourneville's tuberous sclerosis. Bilateral angiomyolipoma
      is exceptional. The authors report a case of bilateral renal angiomyolipoma in a
      33-year-old patient presenting with haemorrhagic shock. In the light of this case
      and a review of the literature, the authors discuss the diagnostic and
      therapeutic aspects of this disease.

PMID- 14650307
TI  - [Tumor of upper urinary tract in renal polycystic disease].
AB  - Upper urinary tract tumours are exceptional in the context of renal polycystic
      disease. The authors report the case of Mrs B. F., 56 years old, who presented
      with left loin pain associated with haematuria. Clinical examination was normal
      and ultrasound examination revealed bilateral renal polycystic disease with a
      mass in the left renal sinus. CT urography showed a tumour arising from the renal
      pelvis suggestive of an upper urinary tract tumour. The laboratory assessment
      revealed normal renal function and normal urine cytology. Treatment consisted of
      radical nephroureterectomy with resection of a bladder cuff. Histological
      examination revealed a urothelial tumour of the renal pelvis with negative
      surgical margins. In the light of this case, the authors discuss the diagnostic
      difficulties and specificities, the treatment and the outcome of this unusual
      clinical association.

PMID- 14650308
TI  - [Primary adenocarcinoma of the bladder and renal transplantation].
AB  - Primary bladder adenocarcinoma is a rare tumour which represents between 0.5% and
      2% of malignant bladder tumours. The incidence of malignant tumours is increased
      in renal transplant recipients. The combination of primary bladder adenocarcinoma
      and renal transplantation is exceptional. The authors report a case of primary
      bladder adenocarcinoma in a 34-year-old patient who had undergone renal
      transplantation 5 years previously. In the light of this case, the authors
      discuss the various cases reported in the literature and the specific management
      of this rare tumour.

PMID- 14650309
TI  - [Bladder leiomyoma. Diagnostic and therapeutic approach].
AB  - The authors report their experience of four cases of bladder leiomyoma. Although
      MRI is currently the reference radiological examination, the diagnosis must be
      confirmed by histological examination. The various diagnostic steps and resulting
      therapeutic indications are described with a review of the literature.

PMID- 14650310
TI  - [Ureteral duplication in a boy].
AB  - The authors report the case of a 2-year-old boy presenting with a rare form of
      urethral duplication (Effmann and Lebowitz type III) associated with other
      urinary tract abnormalities and renal failure. This child died despite
      appropriate therapeutic management.

PMID- 14650311
TI  - [Testicular metastasis of alveolar rhabdomyosarcoma: clinical case of a 19-year
      old man].
AB  - The authors report a case of a 19-year-old man with alveolar rhabdomyosarcoma
      with an unusual clinical presentation. The diagnosis was established on lymph
      node biopsy performed on admission of the patient in a context simulating
      leukaemia. The patient achieved complete remission in response to high-dose
      chemotherapy. A recurrence in the form of an intratesticular metastasis
      demonstrated a periorbital tumour that was probably the primary tumour. The
      authors present the radiological and histological findings and a molecular
      biology study of the testicular metastasis, eliminating a primary testicular
      tumour.

PMID- 14650312
TI  - [Scrotal reconstruction by inguinal flap after Fournier's gangrene].
AB  - OBJECTIVES: The authors propose the use of a pedicle inguinal flap for
      reconstruction of the scrotal region after wide tissue resection following
      gangrene of the perineum. MATERIAL AND METHODS: Between 1998 and 2002, the
      authors treated 14 patients by surgical debridement following Fournier's perineo
      perianal cellulitis. The authors used a pedicle inguinal flap in two patients
      with complete resection of the scrotal sac. RESULTS: Clinical examination at 3
      years showed a good functional and aesthetic result. The trophicity and
      sensitivity of the neo-scrotum and testes were normal. CONCLUSIONS: The inguinal
      flap proposed by that authors allows cover of the scrotal region with relatively
      thick, sensitive tissue with limited scarring and functional sequelae.

PMID- 14650313
TI  - [The "prince of surgery," Antoine Jobert de Lamballe (1799-1867) and the first
      radical cure of vesico-vaginal fistulae with his method of cystoplasty].
AB  - Jobert de Lamballe, consultant-physician of Louis-Philippe, first surgeon of
      Napoleon III, Professor of Clinic Surgery, President of the Academy of medicine
      and member of the Institute, was a very inventive research worker and provided to
      the surgical technique of his time an essential contribution to the area of
      intestinal, urologic, gynecologic and plastic surgery. He died, in 1867, by
      general paresis.

PMID- 14650314
TI  - [Fallouts in human physiology studies on weightlessness].

PMID- 14650315
TI  - [Preventive medicine in geriatrics].
AB  - This paper gives a summary of check-up and preventive recommendations for
      elderly. It concerns screening, vaccination, chemoprophylaxy, and counseling. It
      is mainly based on the recommendations of the U.S. Preventive Services Task
      Force. It approaches the screening of hypertension, visual and auditive
      impairment, breast, colorectal, cervical, prostate cancers, about dyslipidemia,
      depression, osteoporosis, vaccination against influenza, pneumococcal infection,
      and chemoprophylaxy by estrogen, raloxifene, acetylsalicylic acid. There is also
      counseling in the prevention of falls, exercises, and diet. This summary
      underlines the multiple recent changes compared with the 1996 recommendations.

PMID- 14650316
TI  - [Laparoscopy in urology].
AB  - Since the past 10 years, results have established laparoscopy's efficacy. It is
      actually a consistent surgical option for a lot of indications met in urology.
      The rational behind performing laparoscopic procedures includes shorter hospital
      stays, less postoperative pain and a more rapid return to usual activity.
      Drawbacks of laparoscopy include significant learning curve, longer operative
      times and higher overall costs. One particular focus is the oncologic
      applications of laparoscopy for nephrectomy and specially for radical
      prostatectomy. Laparoscopy become nowadays an usual part of the armamenturium of
      urological teams.

PMID- 14650317
TI  - [Primary pulmonary hemangiopericytoma: 2 new cases].
AB  - We describe two new resected cases of primary pulmonary hemangiopericytoma and
      the review of cases published in the period 1954-2002. The first patient has a
      large pulmonary mass of the right apex revealed by scapular pain. The right upper
      lobectomy with free margins reveals hemangiopericytoma. Pelvic and pulmonary
      metastases appear two years after surgery, treated by two series of chemotherapy
      without clinical response. After acute nephrotoxicity controlled by hemodialysis,
      the patient dies with distant metastases three years and an half after
      thoracotomy. The second patient develops dry cough and thoracic pain with
      discovery of a cavitary mass in the right pulmonary field. Fine needle aspiration
      cytology suggests a mesenchymatous lesion. Three months after extended
      pneumonectomy, the intrathoracic tumour relapses and regresses partially under
      chemotherapy. Femoral and brain metastases are irradiated. The patient dies 22
      months after thoracotomy. Histology and immunohistochemistry of both tumours
      closely related to solitary fibrous tumour confirm malignant hemangiopericytoma.
      Primary pulmonary hemangiopericytoma is rare and may be benign or malignant.
      Radical resection is the best treatment. Chemotherapy and radiotherapy may
      improve the prognosis. Compared with lung cancer, the tumour is a slow growing
      mass, often voluminous, with delayed symptoms, very few lymph node dissemination,
      rare brain metastasis, more frequent cutaneous or retroperitoneal dissemination,
      often after long-term and requiring indeed a 10 to 20 years follow-up.

PMID- 14650318
TI  - [Physiopathology of periventricular leukomalacia].
AB  - The term "periventricular leukomalacia" (PVL) usually covers necrotic and/or
      gliotic lesions from perinatal origin occurring in the periventricular ring of
      telencephalic white matter. However focal white matter necrosis is often
      associated to a diffuse white matter disease and to brainstem and grey matter
      lesions, making up the basis of a true encephalopathy. PVLs are diagnosed in 4%
      to 10% of infants born before 33 weeks of gestation. The proportion of PVLs from
      prenatal origin is estimated around one third of cases. Recent progresses in
      neuroepidemiology, developmental neurobiology and imaging methods permitted to
      revisit the pathophysiology of PVLs on a multifactorial basis. The end result of
      these multiple factors seems to be calcium influx due to glutamatergic
      overactivation triggered by cytokines, free radicals, and deficits in
      neurotrophic factors. Periventricular topography can be explained by properties
      of the brain at this specific step of brain development. Carrying motor and
      neuropsychological consequences, PVLs could be the most severe danger for very
      premature brains. Positive rolandic sharp waves recorded on EEG and precocious
      abnormally echogenous periventricular images on ultrasound suggest prospective
      periventricular cysts. Cystic periventricular cavitations certify the diagnosis
      of PVL. More subtle lesions of PVL do not reach the cystic grade and their
      diagnosis is confirmed by MRI. Treatment of infections is already available and
      potentially a tool for prevention. When the overwhelming glutamatergic signal has
      been triggered, neuroprotective agents turning off the excitotoxic cascade,
      including calcium blockers, growth factors and others, are promising therapeutic
      tools.

PMID- 14650319
TI  - [Chronic myeloid leukemia in 2003].
AB  - The recent introduction of imatinib mesylate has deeply changed the treatment of
      chronic myeloid leukemia. This first physiopathology-based therapy, which targets
      the molecular anomaly that gives rise to the disease (the abnormal tyrosine
      kinase activity generated by the fusion protein P210 Bcr-Abl) has demonstrated an
      impressive activity. However, its long-term efficacy remains unknown. On the
      other hand, other treatment modalities, such as stem cell transplantation or
      experimental ones (immunotherapy) are also profoundly evolving. In this review,
      the authors have tried to synthesize the current knowledge of this disease and
      suggest a therapeutic strategy based on the currently available data.

PMID- 14650320
TI  - [Imaging of the month: value of 99mTc MIBI in the assessment of plasmacytoma
      extension].

PMID- 14650321
TI  - [Pioneers in human histocompatibility].

PMID- 14650322
TI  - [Analysis of nuclear and mitochondrial genomes of transplastomic Salpiglossis
      sinuata plants obtained by transfer of transformed plastids from N. tabacum (+S.
      sinuata) cybrid].
AB  - New model system of plastid transformation has been proposed using a wild
      representative of Solanaceae family--S. sinuata. Earlier obtained cybrid plants
      N. tabacum (+ S. sinuata) were used for transformation experiments by PEG
      treatment of protoplasts with aadA gene that confers resistance to spectinomycin.
      Transformed S. sinuata plastome was transferred from N. tabacum (+ S. sinuata)
      cybrid to S. sinuata wild type plants by somatic hybridization. Molecular
      analysis of nuclear and mitochondrial DNA has been performed.

PMID- 14650323
TI  - [Comparative molecular-genetic mapping of genomes of rye (Secale cereale L.) and
      other cereals].
AB  - The genetic map of rye consisting of 149 RFLP, 20 isozyme and 12 microsatellite
      markers was developed. Using the collection of cross-hybridizing probes, the
      presence of multiple translocations in rye genome with respect to wheat and
      barley genomes was shown. However, within large regions of genome a strict
      collinearity of marker order was observed that allow us to use the method of
      comparative mapping for an introduction of new genes. In the developed genetic
      map 18 morphological and breeding-valuable genes mapped in different rye
      populations were integrated. The comparative analysis of homeological loci in
      genomes of Triticeae species as well as in genomes of rice and maize was carried
      out. The genes controlling a number of morphological traits, plant height,
      photoperiodic response and winter/spring growth habit were shown to be conserve
      among cereals and to form clear homoeologous rows.

PMID- 14650324
TI  - [Genetic analysis of the short-stem populations of rye (Secale cereale L.) for
      the plant height trait].
AB  - The process and results of genetic analysis of the short-stem rye populations
      (Secale cereale L.) for the trait "plant height" are described. The analysis has
      been performed with the joint scaling test using data of estimation of the
      parental and hybrid populations developed in the cyclic reciprocal crosses
      between four initial populations. Monogenic, digenic, and trigenic differences
      between parental rye populations for two genes of incomplete dominance and one
      multiallelic gene with additive allelic interaction were determined.

PMID- 14650325
TI  - [Genetic analysis of oat (Avena sativa L.) by joint scaling test].
AB  - Comparing the results of genetic analysis of oat varieties with the method of
      diallel analysis of F1 hybrids and with the joint scaling test the spheres of
      optimal application of both methods were determined. Quantitative estimation of
      genetic parameters forming the phenotypic averages in scaling test develops the
      necessary base for involvement of marker genes for qualitative characters in
      search of QTLs controlling the traits with continuous variation. The crosses
      being the most suitable for further investigation with the aim to identify and to
      allocate the main genes of quantitative traits are indicated.

PMID- 14650326
TI  - [Characteristic of the univalent behavior in a series of monosomic lines of wheat
      Milturum 553 cultivar in the second meiotic division of microsporocytes].
AB  - The investigations fulfilled resulted in defining the character of the univalent
      behavior of each chromosome of the wheat cultivar Milturum 553 in the second
      meiotic division of the microsporocytes. General regularities of the hemizygous
      state of chromosomes in realisation of mechanisms of the changes of pole
      orientation and disjunction of chromatids to the opposite sides has been
      revealed.

PMID- 14650327
TI  - [Effect of gametocidal chromosome 4S' on the phenotype segregation ratio in
      genetic analysis of common wheat lines].
AB  - Using experimental data on genetic analysis of introgressive lines for the
      character "hairy leaf sheath" controlled by the "cuckoo" chromosome 4S1, the
      algorithm for calculation of the theoretical segregation ratio in F2 was
      developed. Segregation distortion is caused by non-viability of the majority of
      gametes lacking the chromosome 4S1. The frequency of functioning gametes without
      the chromosome 4S1 is determined by the probability p versus the theoretically
      expected ratio 7 nonviable: 9 viable ones. Since segregation involves two
      characters, gamete viability and hairiness, the ratio 15 hairy: 1 hairless was
      used as a basis for search of the frequency p by maximum-likelihood method using
      16 populations F2 from crossing the lines differing in the character studied.

PMID- 14650328
TI  - [Genetic control system of the differences in duration of vernalization in winter
      common wheat].
AB  - Hypotheses of differences in genetic control on duration of vernalization for
      winter wheat have been considered. It has been shown that differences in this
      character are controlled by independent Vrd gene system. Monogenic dominant near
      isogenic lines have been created. They differ in two non-allelic Vrd1 and Vrd2
      genes with unequal expression. The response of created lines to photoperiodic
      changes and Vrd genes effects on various agronomic traits have been
      characterized. Vrd genotypes have been identified in a number of winter common
      wheat cultivars.

PMID- 14650329
TI  - [Restriction mapping and variability of 18S-25S ribosomal genes in some species
      of Gentiana genus].
AB  - Mapping of rRNA genes in four species of Gentiana genus has been carried out by
      blot-hybridization method using some restriction endonucleases. The following
      characteristics of Gentiana rDNA structural organization have been revealed: 1)
      interspecific and intragenomic variability of the length of ribosomic repeats; 2)
      conservativity of the transcribed region; 3) variability of the length and
      location of Hind-III site in non-transcribed spacer; 4) interspecific variability
      of the number of copies. Comparative analysis of the constructed restriction maps
      of Gentiana species and some other plants revealed the similarity of restriction
      site location in the transcribed DNA region.

PMID- 14650330
TI  - [Cytogenetic processes in the course of Triticum aestivum and Haynatricum
      hybridization].
AB  - Meiosis in hybrids obtained in direct and return crossings between Haynatricum
      and wheat was studied. In F1 hybrids the possibility of stimulation of
      homoeologous pairing between the chromosomes of T. aestivum and T. dicoccum and,
      probably, H. villosum, if Haynatricum was used as pollinator, has been shown.
      This process is considerably intensified when the genes regulating chromosome
      pairing, in particular ph1b mutation, are used. In reciprocal crosses it was
      shown that wheat genotypes can differently influence on homoeologous chromosome
      pairing. In BC1 and F2 generations the chromosome compositions are determining
      which arise as a result of stochastic processes in premeiotic mitoses and in
      meiosis in F1 hybrids.

PMID- 14650331
TI  - [Recombination frequency in the locus Gli-D1 of common wheat T. aestivum L].
AB  - The recombination frequency at the gliadin locus Gli-D1 of common wheat was
      determined by the maximum likelihood method. Recombination was observed between
      the gene encoding the fastest omega-component of the allele Gli-D1j, and the
      genes encoding the other omega-gliadins of this allele. The frequency of
      recombination was 0.65 +/- 0.18% for the cross between the near-isogenic lines of
      winter common wheat with respect to gliadin loci Gli-D1-4 and Gli-B1-3 and 0.78
      +/- 0.45% for the cross between the varieties Yunnat and B-16.

PMID- 14650332
TI  - [From Lysenkoism to genetics of development (75 years of the research in the
      department of genetics of SGI].

PMID- 14650333
TI  - Dangerous laser article: please proceed with caution.

PMID- 14650334
TI  - Life-enhancing dentistry.

PMID- 14650335
TI  - Jump-start case acceptance through your hygiene department. R-E-A-C-H for
      success.

PMID- 14650336
TI  - OSAP. Meeting your infection control needs.

PMID- 14650337
TI  - Aesthetic correction of an anterior malocclusion with a submicron-filled direct
      composite resin.

PMID- 14650338
TI  - Closing a large central diastema using a pressed ceramic.

PMID- 14650339
TI  - How to be a smile designer, Part 1.

PMID- 14650340
TI  - Back to the future with porcelain veneers.

PMID- 14650341
TI  - The elusive tight contact with composite restorations. How to achieve it.

PMID- 14650342
TI  - Implant surgery and high-frequency currents. Operative indications.

PMID- 14650343
TI  - Single-visit endodontics, Part 2.

PMID- 14650344
TI  - Endodontic therapy using orascopic visualization. An update.

PMID- 14650345
TI  - A review of complete denture therapy for patients with compromised retention.

PMID- 14650346
TI  - Evaluation and management of TMDs, Part 2.
AB  - TMDs are only one of a host of different conditions that are part of the broader
      category of chronic orofacial pain disorders and dysfunctions. Due to
      multifactorial etiologies, it is imperative to adopt a multidisciplinary approach
      when evaluating and treating these patients. Table 1 lists the various conditions
      to consider in the differential diagnosis of orofacial pain disorders.

PMID- 14650347
TI  - How to build your dream practice, Part 2. The next steps.

PMID- 14650348
TI  - Never sell dentistry again!

PMID- 14650349
TI  - Like eating an elephant, computerizing your practice should be done "one bite at
      a time".

PMID- 14650350
TI  - Why should we study human food intake behaviour?
AB  - Several aspects of human eating behaviour may be relevant for identifying
      effective measures to treat or prevent diseases like obesity, diabetes, or the
      metabolic syndrome, whose natural history is strongly influenced by nutritional
      factors. Physiological factors determine hunger, satiety and satiation, and a
      biological learning mechanism supports the acquisition of food likes and
      dislikes. The paradigm of "conditioned taste aversion" refers to the acquisition
      of a strong rejection response after the intake of a food has been followed by
      digestive disorder. Food likes are acquired following the experience of the
      beneficial post-ingestive effects of intake. Physiological mechanisms reinforce
      the liking for energy-rich foods and both environmental and biological conditions
      facilitate "passive overconsumption". Sensory factors are important determinants
      of appetite and food choices from birth to old age. The human newborn exhibits an
      innate repertoire of acceptance or rejection for taste substances. The
      progressive change of sensory functions associated with ageing affects appetite
      and the pleasure of eating. Many individual psychological characteristics affect
      food intake behaviour in a significant way. These include chronic dietary
      restraint, disinhibition, etc. These psychological traits can be objectively
      assessed using validated psychometric instruments. Various stimuli present in the
      environment also affect ingestive behaviours in humans. Portion size is one
      potent environmental determinant of how much a person eats, regardless of hunger.
      The general increase in portion sizes observed in North America over the last
      decades might have played an important role in the rapid rise of obesity
      prevalence. Socio-economic factors also affect food selection and food intake in
      human societies. Factors such as education level and income determine food
      choices and behaviours in a way that does affect the risk of obesity. Behavioural
      science has provided many insights about crucial cause-and-effect relationships
      that affect nutrition and health. Therefore, clinicians and nutritionists cannot
      neglect this important area if they wish to effectively modify the habitual diet
      of individual patients or the general population.

PMID- 14650351
TI  - Influence of polymorphism (RFLP-sstI) at the apolipoprotein C-III gene locus on
      the lipoprotein metabolism and insulin resistance in essential hypertensive
      patients. Interaction between gender and genetic polymorphism.
AB  - BACKGROUND AND AIM: With respect to the general population, hypertensive patients
      show an increase in plasma total cholesterol and triglycerides, a decrease in HDL
      cholesterol (HDLc) and a higher degree of insulin resistance. Apolipoprotein C
      III (apo C-III) plays a regulatory role in the catabolism of triacylglycerol-rich
      lipoproteins. The S2 allele has been associated with elevated plasma
      triglycerides concentration, blood pressure and increased risk of myocardial
      infarction, all of which are characteristic of an insulin resistant state. The
      aim of this study was to investigate the SstI polymorphism of the apo C-III gene
      locus on the lipoprotein metabolism, apolipoproteins and basal glucose and
      insulin levels in essential hypertensive patients. We also examined the influence
      of the S1S2 allele on blood pressure and the interaction of the mutation at the
      apo C-III gene and the gender. METHODS AND RESULTS: We studied 104 essential
      hypertensive patients (59 males and 45 females) determining the carriers of the
      S2 allele of the genetic polymorphism in the apo C-III gene by polymerase chain
      reaction, lipoprotein metabolism by standard laboratory methods and
      ultracentrifugation, apolipoproteins A-I and B by immunoturbidimetry and basal
      glucose and insulin levels by enzymatic method and radioimmunoassay,
      respectively. The frequency for the carriers of the SstI minor allele S2 (S1S2
      genotype) was 0.17. Patients with the rare S2 allele compared with those with
      S1S1 allele showed higher plasma triglycerides, total cholesterol and apo B
      (255.9 +/- 114.6 vs 135.8 +/- 89.1; 250.6 +/- 56.6 vs 214.8 +/- 47.9 and 128.7 +/
      34.8 vs 103.1 +/- 28.6 respectively). Furthermore, basal glucose, insulin levels
      in S2 allele, and the rate Tg-VLDL/HDLc were increased in the same group.
      Subgroup analysis revealed that the association between these polymorphism and
      lipoprotein metabolism, apolipoprotein and basal glucose and insulin levels
      occurred predominantly in females. A study on the effect of the interaction
      between this mutation with gender revealed an additive effect on changes in total
      triglycerides levels. However age, blood pressure and body mass index were
      similar in both groups of patients (S1S1 and S1S2 genotypes). CONCLUSIONS: These
      results provide evidence of interaction between gender and the Sst1 polymorphism
      of the apo C-III on lipoprotein metabolism and insulin resistance in essential
      hypertensive patients. However, the studied mutation does not contribute to blood
      pressure levels in essential hypertensive patients (crossover study).

PMID- 14650352
TI  - Physical activity modulates effects of some genetic polymorphisms affecting
      cardiovascular risk in men aged over 40 years.
AB  - BACKGROUND AND AIM: Several genetic polymorphisms have been found to be involved
      in cardiovascular risk, and many studies have documented the beneficial effect of
      systematic physical activity (PA) on the cardiovascular system. Our aim was to
      investigate the interactive effects of PA and genetic background on plasma lipids
      and homocysteine (tHcy) levels. METHODS AND RESULTS: Clinical and metabolic
      parameters, dietary intakes and some polymorphisms of the genes involved in
      cardiovascular risk (Apo E, fatty acid binding protein-2, Apo AII, hepatic lipase
      and methylene tetrahydrofolate reductase) were determined in 100 men aged over 40
      years who cycle 120-150 Km/week and 100 age-matched sedentary controls. The
      physically active subjects had lower concentrations of plasma LDL cholesterol
      (LDL-C), triglyceride (TG), Apo B, glucose and tHcy, and higher concentrations of
      plasma HDL cholesterol (HDL-C) and Apo AI than the sedentary men; they also had
      larger LDL particle sizes (LDLs). The LDL-C and Apo B raising effect of the Apo E
      epsilon 4 allele detectable in the sedentary subjects was totally absent in the
      cyclists, in whom the LDL-C and Apo B lowering effect of the epsilon 2 allele was
      observed. PA blunted the TG-raising effect of the Apo AII-265TT genotype, and
      amplified the HDL-C raising effect of the HL-250AA genotype. PA had a small but
      significant lowering effect on plasma tHcy adjusted for folate levels in subjects
      with the 677TT genotype of the MTHFR gene. CONCLUSIONS: Extended high-intensity
      PA in men aged over 40 years may modify their metabolic cardiovascular risk
      factors even in the presence of some unfavourable genotypes.

PMID- 14650353
TI  - Citizens and family doctors facing awareness and management of traditional
      cardiovascular risk factors: results from the Global Cardiovascular Risk
      Reduction Project (Help Your Heart Stay Young Study).
AB  - BACKGROUND AND AIM: The numerous guidelines and multiple approaches to managing
      cardiovascular risk factors have reduced the number of fatal events but not the
      incidence of cardiovascular disease (CVD). One rarely explored aspect is the
      extent to which individuals perceive their own risk in relation to their
      education and history of CVD. Furthermore, Italy has a State-based Health System,
      in which family doctors (FDs) may be an extremely useful and relatively low cost
      resource for risk management, but the degree of their involvement in individual
      CVD risk management has not been previously assessed. METHODS AND RESULTS: The
      Department of Clinical and Experimental Medicine of Federico II University,
      Naples, Italy, and the Neapolitan Section of the Italian Society of Family
      Doctors (SIMG), developed an epidemiological survey to evaluate the level and
      awareness of CVD risk in subjects in the urban area of Naples, and the degree of
      involvement of FDs in CVD risk management. During a period of a few months, the
      subjects who visited their FDs were invited to respond to a standard self
      explanatory questionnaire, and the FDs were required to provide quantitative
      information concerning the CVD risk factors of each enrolled subject from their
      databases in order to assess global CVD risk. The data included cholesterol and
      blood pressure (BP) levels, and had to be collected within six months of the
      visit; if the date were missing, the fact was recorded. The present analysis was
      based on data concerning the 5,687 subjects who had entered the study by January
      2002, 7.6% of whom reported CVD (myocardial infarction (MI), stroke, angina,
      cerebral transient ischemic attack: CD+) and 92.4% did not (CVD-). MI was the
      most frequent CVD, and 18% of the CVD+ cases reported more than one non-fatal
      cardiovascular event. On average, the CVD+ subjects were older and more often
      men. After adjusting for age and FD, they also had a higher body mass index (BMI)
      and prevalence of obesity, higher self-reported BP, a lower education level, and
      more often referred high cholesterol levels, hypertension and diabetes. On the
      contrary, the proportion of smokers was higher in the CVD- group. Among the
      subjects who declared that they did not have a high cholesterol level, 11%
      reported recent values of > 200 mg/dL. The FDs of 36% of the cases were unable to
      assess the individual global CV risk level using quantitative data from their
      electronic databases. The most frequently missing information was the level of
      total cholesterol. Missing data were more frequent in the CVD- than the CVD+
      subjects, regardless of age and FD. CONCLUSIONS: The results of our study suggest
      that the awareness of CVD risk among subjects is somewhat vague. The FDs were
      generally able to provide a quantitative assessment of CVD risk in their
      patients. CVD risk prevention programmes may be more successful if they stress
      knowledge and awareness in the population, and stimulate FDs to undertake more
      stringent quantitative assessments of CVD risk factors.

PMID- 14650354
TI  - Relevance of different apolipoprotein content in binding of homocysteine to
      plasma lipoproteins.
AB  - BACKGROUND AND AIMS: In plasma the atherogenic thiol homocysteine (Hcy)
      circulates either free or bound to proteins (Pb-Hcy). The present study sets out
      to evaluate the lipoprotein-Hcy (LP-Hcy) binding in vivo and the possible
      influence of different apolipoprotein content in this binding, being lipoprotein
      oxidation a possible mechanism of Hcy-induced damage. METHODS AND RESULTS: In 34
      healthy subjects we assayed fasting plasma lipoprotein and correspondent
      apolipoprotein (apo A-I, apo A-II, apo C-II, apo C-III, apo B, apo(a) and apo E
      content, and Hcy bound to different plasma protein fractions; moreover ten
      subjects underwent an oral methionine load in order to evaluate possible
      "dynamic" modifications of Pb-Hcy and LP-Hcy after induction of
      hyperhomocysteinemia. Pb-Hcy (mean values 9.22 +/- 1.7 mumol/L) represented about
      78% of total plasma Hcy (mean values 11.8 +/- 1.8 mumol/L). Pb-Hcy distribution
      between the different fractions was as follows (mumol/L): VLDL = 0.25 +/- 0.08
      (2.7%); LDL = 0.88 +/- 0.22 (9.5%); HDL = 1.40 +/- 0.36 (15.2%); fractions with
      density greater than 1.21 g/mL (Lipoprotein-Free Protein Fraction, LPDS) = 6.7 +/
      1.2 (72.6%). Hcy/protein ratios (nmol/mg of protein) in each protein fraction
      were: VLDL = 0.32 +/- 0.19, LDL = 0.43 +/- 0.37, HDL = 0.26 +/- 0.18, LPDS < 0.1,
      thus suggesting a higher binding capacity for Hcy by VLDL and LDL. These data
      were confirmed by the higher increase in Hcy content in LDL and VLDL (76 and 90%,
      respectively vs 36% and 3.1% for HDL and LPDS fractions) after
      hyperhomocysteinemia. Lp-Hcy binding significantly correlated with the apo B
      content of VLDL and LDL and Apo A-I content of HDL. CONCLUSIONS: An important
      fraction of plasma Hcy circulates bound to LP (about 27% of Pb-Hcy); VLDL and LDL
      show the highest binding capacity for Hcy, probably due to their content in Apo
      B, a possible high capacity binding site for Hcy.

PMID- 14650355
TI  - Increase of inflammatory state in overweight adults with combined hyperlipidemia.
AB  - BACKGROUND AND AIM: Elevated levels of acute phase reactants are found in
      patients with cardiovascular disease. It is suggested that adipose tissue is a
      determinant of a low level of inflammatory state in overweight persons. The aim
      of the study was to determine, whether combined hyperlipidemia, which is an
      important factor of atherosclerosis, has influence on the inflammatory response
      in overweight adults. METHODS AND RESULTS: Levels of soluble cell adhesion
      molecules sICAM-1, sE-selectin and sP-selectin, PAI-1 Ag (by Elisa test),
      orosomucoid (ORM) and transferrin (TRF) (by microturbidimetry) and fibrinogen
      (FBG) according to Clauss were examined in peripheral blood of overweight adults
      (n 33, body mass index 27.1 +/- 1.8 kg/m2) with combined hyperlipidemia and in
      equal numbers of age, sex and BMI matched non-hyperlipidemic group. Overweight
      adults with combined hyperlipidemia had significantly higher plasma levels of
      sICAM-1 (376.5 +/- 107.4 ng/mL vs 239.3 +/- 60.4 ng/mL; p < 0.001), sE-selectin
      (70.4 +/- 20.2 ng/mL vs 48.5 +/- 25.6 ng/mL; p = 0.005), sP-selectin (228.2 +/-
      88.6 ng/mL vs 123.1 +/- 45.3 ng/mL; p < 0.001) and positive acute phase proteins
      ORM (0.82 +/- 0.16 g/L vs 0.64 +/- 0.20 g/L; p = 0.005), FBG (3.42 +/- 0.54 g/L
      vs 2.74 +/- 0.57 g/L; p = 0.037) and PAI-1 Ag (97.9 +/- 40.6 ng/mL vs 56.4 +/-
      25.6 ng/mL; p < 0.05), and a decrease of negative acute phase protein TRF (2.14
      +/- 0.40 g/L vs 2.77 +/- 0.45 g/L; p < 0.001) compared to the results in
      overweight non-hyperlipidemic controls. CONCLUSIONS: It is suggested that
      overweight adults have an increase of inflammatory response dependent on
      hyperlipidemia. It was apparent from the elevation of sE--selectin, sP--selectin
      and sICAM-1 and from an increase of systemic inflammatory response according to
      the increase of "positive" acute phase proteins (APRs) and the decrease of
      "negative" APR protein levels in these patients.

PMID- 14650356
TI  - Effect of chronic treatment with beta-blockers on resting energy expenditure in
      obese hypertensive patients during a low-calorie and physical training program.
AB  - BACKGROUND AND AIM: To evaluate whether chronic treatment with beta-blockers
      influences resting energy expenditure (REE) and weight loss after a period of
      diet and physical activity in obese hypertensive patients. METHODS AND RESULTS:
      Seventy-eight obese hypertensive patients (24 males and 54 females) aged 53.7 +/-
      11.1 years with mean BMI of 42.4 +/- 5.8 kg/m2 were enrolled. Thirty-eight
      patients were using beta-blockers while 40 patients who had not received beta
      blockers in the past 6 months were the control group. REE was measured with
      indirect calorimetric method. Total body fat mass, total body fat-free mass (FFM)
      and total body water (W) were determined by bioelectrical impedance analysis.
      Patients and controls underwent a structured physical training program and a
      hypocaloric diet for a period of 31.6 +/- 10.6 days. Measured REE in patients
      taking beta-blockers was 1818 +/- 309 kcal/24 h and 1853 +/- 348 kcal/24 h in
      patients not taking beta-blockers; p = non significant. Weight and BMI loss were
      similar between the two groups and were respectively -6.43 +/- 2.62 kg and -2.42
      +/- 0.91 kg/m2 in the beta-blocker group and -7.49 +/- 3.10 kg, -2.78 +/- 1.03
      kg/m2 in the non beta-blocker group. Body composition was similar in the two
      groups. In the comparison between patients treated with selective beta 1
      adrenoceptors blockers and non selective beta-blockers we found a significant
      difference in REE (1704 +/- 283 vs 1974 +/- 278; p = 0.012) and in weight loss (
      5.6 +/- 2.4 vs -7.5 +/- 2.7; p = 0.048) at the end of study. CONCLUSIONS: Beta
      blockers are not associated with a lower REE in obese subjects compared to other
      antihypertensive treatment. Use of non selective beta-adrenergic blockers is
      associated with a higher REE and weight loss compared to use of selective beta 1
      adrenergic blockers. Non selective beta-blockers could be indicated among first
      choice drugs in hypertensive severely obese subjects without contraindications to
      beta-blockade.

PMID- 14650357
TI  - Secondary prevention of coronary artery disease in high-risk diabetic patients.
AB  - BACKGROUND AND AIM: To compare guideline implementation and the actual delivery
      of secondary prevention for coronary artery disease in the cohort of Italian
      diabetic patients enrolled in the DAI study. METHODS AND RESULTS: The DAI study
      is a multicentre cohort study of the prevalence and incidence of macroangiopathic
      events among 19,570 type 2 diabetic patients attending 201 Diabetic Care Units.
      For this study, we selected 1,475 subjects with a history of myocardial
      infarction, coronary artery bypass graft or percutaneous transluminal coronary
      angioplasty at enrollment. Only 25% of the coronary patients in secondary
      prevention were receiving lipid-lowering drugs, and 20% were receiving beta
      blockers. None of the patients in 54/185 Diabetic Care Units were on statins, and
      none in 82/185 Units were on beta-blockers. Multivariate analysis showed a
      positive correlation between the number of treatments and the taking of statins,
      and a negative correlation with age. CONCLUSION: Our data highlight a gap between
      the therapeutic guidelines and actual treatment, with wide variability in the
      delivery of secondary prevention across Units. The out-of-pocket cost of
      medication, daily treatment burden and geographic area can be ruled out as
      possible explanatory factors. Physicians' prescription attitudes may be a
      possible reason.

PMID- 14650358
TI  - Role of the natriuretic peptide system in lipogenesis/lipolysis.
AB  - AIM: There is recent evidence that the natriuretic peptide (NP) system promotes
      adipose tissue lipolysis in primates. This effect is mediated by the interaction
      of NP with its active receptors through guanylyl cyclase activation and cGMP
      production. This review will briefly focus on the new aspects of NP
      pathophysiology in man. DATA SYNTHESIS: NP receptors have been described in
      rodent adipocytes, and the expression of their mRNA is found in human adipose
      tissue together with high level of ANP binding sites. In isolated fat cells,
      atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were able to
      stimulate lipolysis as much as isoproterenol, a non-selective beta-adrenergic
      receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest
      lipolytic effect. The potent lipolytic effect of NP has also been confirmed in
      samples of abdominal adipose tissue from healthy subjects. The potency order of
      the lipolytic effect (ANP > BNP > CNP) and ANP-induced cGMP production supported
      the presence of type A natriuretic peptide receptor in human fat cells. The
      effect of NP on lipid metabolism is confirmed by the fact that intravenous ANP
      infusion is followed by plasma NEFA and glycerol concentration increase
      (reflecting lipid mobilisation). CONCLUSIONS: The NP system seems to play an
      important role in lipid metabolism, possibly affecting the pathophysiology of
      obesity and obesity-related disorders, such hypertension. Further studies,
      however, are needed to completely establish the mechanisms involved in NP-induced
      lipolysis and the real relevance of this new pathway specific of primates.

PMID- 14650359
TI  - Tramadol--the impact of its pharmacokinetic and pharmacodynamic properties on the
      clinical management of pain.
AB  - Tramadol (CAS 36282-47-0) plays an important role in the management of pain. With
      its dual mechanism of action (opioid agonist; weak noradrenaline and serotonin
      reuptake inhibitor) tramadol provides a kind of combined/adjuvant pain therapy.
      Besides its proven clinical efficacy tramadol is a safe drug as respiratory
      depression, cardiovascular side effects, drug abuse and dependence are of minor
      clinical relevance, unlike some other opioids. Following oral administration the
      bioavailability of tramadol is high (70-90%) and with new slow release
      preparations twice daily administration enables effective pain control. Tramadol
      is characterised by low plasma protein binding (20%) and quite extensive tissue
      distribution (apparent volume of distribution about 3 l/kg). Elimination is
      primarily by the hepatic route (metabolism by CYP2D6 to an active metabolite and
      by CYP3A4 and CYP2B6) and partly by the renal route (up to 30% of dose).
      Elimination half-lives of the active agents range between 4.5 and 9.5 h and total
      plasma clearance of tramadol is moderately high (600 ml/min). The interaction
      potential of tramadol is neglectable, as it does not affect the disposition of
      other drugs. It should be taken into account that inducers (e.g. carbamazepine)
      or inhibitors (e.g. quinidine for CY2D6) of drug metabolism might modify the
      elimination of tramadol. Likewise, if kidney (creatinine clearance below 30
      ml/min) or hepatic function is severely impaired, some dosage reduction
      (approximately by 50%) or extension of the dosage interval should be considered.
      In conclusion, tramadol is an effective and safe analgesic with a very low
      interaction potential. Therefore it represents a drug of first choice if moderate
      to severe pain states have to be treated in pediatric, adult and elderly patients
      including those with poor cardiopulmonary function.

PMID- 14650360
TI  - Effect of ozagrel, a selective thromboxane A2-synthetase inhibitor, on cerebral
      infarction in rats. Comparative study with norphenazone, a free-radical
      scavenger.
AB  - The effects of ozagrel (CAS 82571-53-7), a thromboxane A2-synthetase inhibitor,
      and norphenazone (CAS 89-25-8), a free-radical scavenger, on cerebral infarction
      were assessed using the suture-induced middle cerebral artery occlusion (MCAO)
      model and a microthrombosis model. In the former model, the middle cerebral
      artery was occluded for 2 h, and the infarction area and volume were evaluated 24
      h after the start of reperfusion. In the latter model, microthrombosis were
      induced by two injections of sodium laurate (interval, 2 days) into the internal
      carotid artery, and the neurologic deficits were evaluated on the day afer the
      2nd injection. Ozagrel at 3 mg/kg decreased both the area and volume of the
      cortical infarction after ischemia-reperfusion of the middle cerebral artery.
      Ozagrel also had suppressive effects on the neurologic deficits in the
      microthrombosis model. Norphenazone at 1 and 3 mg/kg had no clear effects in
      either model. Since the suture-induced MCAO model and the microthrombosis model
      are models for occlusion-reperfusion of the major cerebral arteries and lacunar
      infarction, respectively, these results suggest a highly beneficial effect of
      ozagrel in the clinical therapy for stroke.

PMID- 14650361
TI  - Pharmacokinetics of the new pyrimidine derivative NS-7, a novel Na+/Ca2+ channel
      blocker. 2nd communication: tissue distributions, placental transfer and milk
      secretion of radioactivity after a single intravenous 14C-NS-7 injection to rats.
AB  - Tissue distribution, placental transfer and secretion of radioactivity in milk
      were studied after a single intravenous administration of 0.2 mg/kg of 14C-NS-7
      (4-(fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride, CAS
      178429-67-9), a novel Na+/Ca2+ channel blocker, to rats. Except for white fat in
      male and female rats, tissue radioactivity concentrations 5 min after
      administration were 2 to 100 times the plasma values, evidence that the drug is
      widely distributed throughout the body. Five minutes after administration the
      highest concentration was in the lung followed in order by the adrenal gland,
      kidney and thyroid gland. Concentrations in the cerebral cortex, striatum and
      cerebellum, the target organs of NS-7, were similar and 10 to 18 times the plasma
      concentrations in the male and female rats. Radioactivity concentrations in the
      lungs decreased rapidly. The pancreas had the highest concentration 2 h after
      administration. Concentrations decreased in all the tissues examined as the
      plasma concentration decreased. Maternal and fetal tissue radioactivity
      concentrations were determined after intravenous injection of 14C-NS-7 to
      pregnant rats on the 18th day of gestation. Radioactivity was well and rapidly
      distributed to the maternal tissues, and concentrations in all the tissues tested
      were higher than the plasma concentrations. In the amniotic fluid, however, the
      concentration was lower than in the plasma. In all the fetal tissues tested,
      radioactivity reached a maximum 1 h after administration. The respective fetal
      blood and whole body concentrations were 2 to 6 and 11 to 13 times the maternal
      plasma concentration. Of the fetal tissues tested the liver had the highest
      radioactivity. Decreases in fetal tissue radioactivity concentrations paralleled
      the decrease in the maternal plasma. More than 90% of the radioactivity present
      in the placenta and fetal whole body 1 and 24 h after administration was due to
      the unchanged drug. After intravenous injection of 14C-NS-7 (0.2 mg/kg) to
      lactating rats on the 10-14th day after parturition, radioactivity was excreted
      rapidly into the milk, reaching a maximum that was 4 to 6 times the plasma value
      1 h after injection.

PMID- 14650362
TI  - Studies on the interaction between fibrates and statins using human hepatic
      microsomes.
AB  - To gain a better understanding of the mechanism of drug-drug interaction between
      fibrates and statins, several in vitro experiments were performed. On
      coincubation with several fibrates, pitavastatin (CAS 147526-32-7) did not
      displace fibrates from their protein binding in human plasma. The presence of
      gemfibrozil (CAS 25812-30-0) inhibited the metabolism of statins (cerivastatin
      (CAS 145599-86-6) and atorvastatin (CAS 134523-00-5)) remarkably. However, the
      increase of the unchanged form was fairly small for pitavastatin. The metabolic
      profile of gemfibrozil was also investigated. The cytochrome P (CYP) enzyme
      CYP2C9 plays a major role in the metabolism of gemfibrozil. Gemfibrozil showed a
      high affinity for CYP enzymes and a relatively high metabolism velocity.
      Moreover, several inhibitory effects of gemfibrozil on CYP-mediated metabolism
      were detected--in contrast to other fibrates. Although the mechanism of the drug
      drug interaction was not completely clarified, it is suggested that the increase
      of plasma concentration caused by the co-administration of gemfibrozil and
      statins is at least partially due to the inhibition of the CYP-mediated
      metabolism.

PMID- 14650363
TI  - Comparison of the effects of sitostanol, sitostanol acetate, and sitostanol
      oleate on the inhibition of cholesterol absorption in normolipemic healthy male
      volunteers. A placebo controlled randomized cross-over study.
AB  - Feeding of margarines containing sitostanol (CAS 19466-47-8), sitostanol acetate
      (CAS 73052-08-1), sitostanol oleate (CAS 107615-79-2), or placebo (equivalent of
      0.5 g of sitostanol t.i.d) on cholesterol absorption and serum lipids were
      studied in 10 normolipemic volunteers in a randomized double blind cross-over
      trial. The study was divided into an open one-week run-in phase and four one-week
      treatment periods. Each treatment week was followed by a two-week washout period.
      Measurements of cholesterol absorption was performed by the continuous isotope
      feeding method using stable isotope labeled cholesterol and sitostanol.
      Cholesterol absorption during placebo, sitostanol, sitostanol acetate and
      sitostanol oleate feeding averaged 41.6 +/- (SD) 8.0, 10.2 +/- 6.6, 17.0 +/- 6.7,
      and 20.5 +/- 5.3%, respectively (p < 0.001 for all against placebo). Low density
      lipoprotein (LDL) cholesterol was proportionally reduced by 22 (p < 0.001), 14 (p
      < 0.05), and 8% (ns). Absorption efficiency was significantly lower with free
      sitostanol than with sitostanol acetate or oleate (p < 0.01). Percent reduction
      in cholesterol absorption with all preparations compared to placebo correlated
      positively with the percent reduction in LDL cholesterol (r = 0.404; p < 0.03).
      The results indicate that unesterified sitostanol is more effective in inhibiting
      cholesterol absorption and reducing LDL cholesterol than the acetate or oleate
      esters.

PMID- 14650364
TI  - Clinical effects of long-term administration of pranlukast, a leukotriene
      receptor antagonist, on adult patients with bronchial asthma.
AB  - Eighty-one adult patients with bronchial asthma who suffered from an unstable
      peak expiratory flow rate (PEFR) and asthmatic attacks that developed at
      irregular intervals in spite of inhaling beclometasone dipropionate (CAS 5534-09
      8, BDP) in excess of 400 micrograms/day were treated with pranlukast (CAS 103177
      37-3, Onon) 450 mg/day for 1 to 2 years and the clinical effects of its long-term
      administration were studied. The patients were divided into 3 groups: Group I
      with drug effect seen on peak expiratory flow rate (PEFR) in a short-term; Group
      II showing long term PEFR improvement; and Group III with no sustained
      improvement in PEFR. Those in the first two groups continued oral medication for
      2 years, while those of the third group withdrew from medication after one year
      and their clinical course was observed. The evaluation parameters were: PEFR,
      frequency of beta 2-stimulant inhalation, number of night time visits to health
      service facilities, quantity of inhalation steroids used, amount of oral steroids
      used at fixed intervals, peripheral eosinophil count, serum eosinophil cationic
      protein (ECP) concentration and FEV1.0. In Group I, the frequency of beta 2
      stimulant inhalation, number of night time visits to health service facilities,
      quantity of inhalation steroids used, and the amount of oral steroids used at
      fixed intervals were reduced; and after two years, the frequency of beta 2
      stimulant inhalation and quantity of inhalation steroids used were further
      reduced. In Group II, reductions were seen in the peripheral eosinophil count and
      serum ECP level. The asthmatic severity shifted from step 3 to 2 in 12 patients
      and from step 4 to 3 in 4 patients in Group I; and from step 3 to 2 in 3 patients
      in Group II. In Group III, an increase in the number of night time visits to
      health service facilities after the medication was interrupted and a rise in the
      serum ECP concentration were recognized.

PMID- 14650365
TI  - Synthesis and studies of 1,2-dihydroquinoline derivatives as inhibitors of lipid
      peroxidation.
AB  - A series of new spiro[naphto[2,1-c][2,7]naphtiridine-5,4'-piperidine] derivatives
      was prepared. Biochemical investigations revealed that all members of this series
      were potent inhibitors of both NADPH- and Fe(2+)-dependent lipid peroxidation
      (IC50 < 10 mumol/l) in rat brain microsomes and rat brain homogenate,
      respectively.

PMID- 14650366
TI  - Clinical study on the dose-effect relationship of a nifuratel-nystatin
      combination in the treatment of vulvo-vaginal infections.
AB  - OBJECTIVE: The dose-effect relationship of nifuratel (CAS 4936-47-4) + nystatin
      (CAS 1400-61-9, CAS 34786-70-4) (Macmiror Complex) in topical treatment of vulvo
      vaginitis was studied. METHOD: Sixty patients with Trichomoniasis and/or
      Candidiasis were randomized to: 1) nifuratel 125 mg/nystatin 50000 IU, 2)
      nifuratel 250 mg/nystatin 100000 IU, 3) nifuratel 500 mg/nystatin 200000 IU.
      Undistinguishable ovules were intravaginally applied qd for 10 days. The dose
      effect relationship was assessed by ANCOVA. RESULT: After 5 days the
      microbiological cure rate occurred in 10% of patients in the least dose, in 40%
      in the middle dose and in 85% in the highest dose group (P = 0.000). After 10
      days of treatment, the microbiological cure rate increased to 45%, 84%, and 95%,
      respectively (P = 0.007). Clinical signs and symptoms gradually disappeared in a
      dose- and time-dependent manner. No relapse has been observed after 10 day-follow
      up on 46 patients. CONCLUSION: The results confirmed a linear relationship
      between nifuratel + nystatin dose and effect. The least effective dose was
      nifuratel 250 mg + nystatin 100,000 IU once daily for 5 days and the best dose in
      terms of risk/benefit ratio was nifuratel 500 mg + nystatin 200,000 IU once daily
      for 5 days.

PMID- 14650367
TI  - Synthesis, in vitro/in vivo antifungal evaluation and structure-activity
      relationship study of 3(2H)-pyridazinones.
AB  - The synthesis, in vitro/in vivo antifungal evaluation and a structure-activity
      relationship (SAR) study of 3(2H)-pyridazinones was carried out. The results
      reported here may be helpful in the structural identification and understanding
      of the minimum structural requirements for these molecules acting as antifungal
      agents. In addition, the most active structure in this series was tested for its
      capacity of inhibiting Saccharomyces cerevisiae beta 1,3-glucan synthase and
      chitin synthase, enzymes that catalyze the synthesis of the major polymers of the
      fungal cell wall.

PMID- 14650368
TI  - Where have we been? How have we done?

PMID- 14650369
TI  - Modifiable risks present an opportunity for improvement.

PMID- 14650370
TI  - Cardiovascular risk factor control and treatment patterns in primary care.
AB  - Previous research has shown that controlling hypertension and other
      cardiovascular (CV) risk factors reduces the number of CV events and
      racial/ethnic health disparities. The objectives of this study were to assess CV
      risk factor treatment, control, and disparities among patients with hypertension
      using data from retrospective medical record audits. Data were obtained from 63
      primary care sites with 201 providers. In 49% of 35,940 patients with
      hypertension, the last blood pressure reading was less than 140/90 mm Hg. In 62%
      of 18,627 patients who also had dyslipidemia, low-density lipoprotein cholesterol
      was less than 130 mg/dL. In 49% of 6,616 patients with hypertension and diabetes,
      glycosylated hemoglobin levels were less than 7%. Multiple risk factor control
      was rare, especially among women and African Americans. It appears that programs
      to improve CV risk factor control using audit and feedback in primary care are
      feasible and instructive.

PMID- 14650371
TI  - The health insurance crisis in the United States: lack of access and the ripple
      effect.
AB  - America's health care system is in crisis. Many individuals are not offered
      health insurance or cannot afford it, thereby increasing the number of uninsured
      who have no stable source of care other than the emergency room. In turn, the
      costs associated with those who lack health insurance ripple to providers who end
      up funding a proportion of uncompensated care, thereby financially crippling the
      bottom line. The lack of access to proper care experienced by the uninsured also
      has a downstream effect on the insured population, threatening the quality of and
      access to health care for all Americans.

PMID- 14650372
TI  - Arbitration agreements in health care nursing home contracts.
AB  - Increasingly, long-term care facilities are adopting alternative dispute
      resolution measures, such as arbitration, in admission contracts. Whereas
      avoiding the onus of civil lawsuits is understandable, nursing homes must ensure
      that the arbitration wording in the contract is precise, enforceable, and most
      importantly, pursuant to state and federal laws, regulations, and guidelines.
      Otherwise, the contract itself may be the subject of a court action.

PMID- 14650373
TI  - Drug disposition analysis: a comparison between budesonide and fluticasone.
AB  - The characterisation of distribution and elimination properties of a drug is
      usually done using parameters like clearance and distributional volumes. To
      refine this characterisation, in this paper, we use drug disposition analysis to
      compare the distribution and elimination of the two glucocorticosteroids
      budesonide and fluticasone propionate, known to differ in this respect. This
      gives a more detailed description of the well known differences in distributional
      volumes using concepts like mean residence time and fraction of dose outside the
      central compartment. It clearly shows that fluticasone, although having lower
      plasma concentrations, still resides in the body in appreciable quantities.

PMID- 14650374
TI  - Comparison of the pharmacokinetics of S-1, an oral anticancer agent, in Western
      and Japanese patients.
AB  - OBJECTIVE: S-1 is an oral anticancer agent combining tegafur (FT), a prodrug of 5
      fluorouracil (5-FU), with potassium oxonate (oteracil) and gimeracil (CDHP)
      respectively to mitigate gastrointestinal toxicity and increase the half-life of
      5-FU. This article presents a population pharmacokinetic analysis of these four
      compounds in Western cancer patients. The second objective was to compare the
      pharmacokinetics of S-1 in Western and Japanese patients. METHODS: A single dose
      (25-45 mg/m2) of S-1 was administered to 60 patients. In each patient, 6
      concentrations of FT, 5-FU, oteracil and CDHP were measured over 24 hr. Using
      NONMEM, oteracil and CDHP were analyzed separately, and the individual estimates
      of CDHP parameters were included in the joint analysis of FT and 5-FU. We used
      validation techniques to assess differences between the two populations, and
      finally we compared the exposures in Western and Japanese patients using
      simulations. RESULTS: A compartmental model describing the PK of the 4 compounds
      was developed. The influence of CDHP on the elimination of 5-FU was well
      described by an enzymatic inhibition model. The model provided a good fit for all
      compounds. The pharmacokinetics for 5-FU and oteracil were similar between
      Western and Japanese patients, but apparent differences in exposure to 5-FU
      resulted from different total doses due to different body sizes.

PMID- 14650375
TI  - Reduction and lumping of physiologically based pharmacokinetic models: prediction
      of the disposition of fentanyl and pethidine in humans by successively simplified
      models.
AB  - Physiologically based pharmacokinetic (PBPK) models can be used to predict drug
      disposition in humans from animal data and the influence of disease or other
      changes in physiology on the pharmacokinetics of a drug. The potential usefulness
      of a PBPK model must however be balanced against the considerable effort needed
      for its development. Proposed methods to simplify PBPK modeling include
      predicting the necessary tissue:blood partition coefficients (kp) from
      physicochemical data on the drug instead of determining them in vivo, formal
      lumping of model compartments, and replacing the various kp values of the organs
      and tissues by only two values, for "fat" and "lean" tissues, respectively. The
      aim of this study was to investigate the effects of simplifying complex PBPK
      models on their ability to predict drug disposition in humans. Arterial plasma
      concentration curves of fentanyl and pethidine were simulated by means of a
      number of successively reduced models. Median absolute prediction errors were
      used to evaluate the performance of each model, in relation to arterial plasma
      concentration data from clinical studies, and the Wilcoxon matched pairs test was
      used for comparison of predictions. An originally diffusion-limited model for
      fentanyl was simplified to perfusion-limitation, and this model was either
      lumped, reducing 11 organ/tissue compartments to six, or changed to a model based
      on only two kp values, those of fat (used for fat and lungs) and muscle (used for
      all other tissues). None of these simplifications appreciably changed the
      predictions of arterial drug concentrations in the 10 patients. Perfusion-limited
      models for pethidine were set up using either experimentally determined
      [Gabrielsson et al. 1986] or theoretically calculated [Davis and Mapleson 1993]
      kp values, and predictions using the former were found to be significantly
      better. Lumping of the models did not appreciably change the predictions;
      however, going from a full set of kp values to only two ("fat" and "lean") had an
      adverse effect. Using a kp for lungs determined either in rats or indirectly in
      humans [Persson et al. 1988], i.e., a total of three kp values, improved these
      predictions. In conclusion, this study strongly suggested that complex PBPK
      models for lipophilic basic drugs may be considerably reduced with marginal loss
      of power to predict standard plasma pharmacokinetics in humans. Determination of
      only two or three kp values instead of a "full" set can mean an important
      reduction of experimental work to define a basic model. Organs of particular
      pharmacological or toxicological interest should of course be investigated
      separately as needed. This study also suggests and applies a simple method for
      statistical evaluation of the predictions of PBPK models.

PMID- 14650376
TI  - Mean hepatic recovery ratio in capacity-limited first-pass effect by three-point
      sampling method.

PMID- 14650377
TI  - Psychiatry in pictures. Photograph of anonymous patient's feet taken May 1998
      near Mozambique-Zimbabwe border.

PMID- 14650378
TI  - Is your skin-prep technique up-to-date?

PMID- 14650379
TI  - Administering acetaminophen safely.

PMID- 14650380
TI  - Does my patient have heparin-induced thrombocytopenia?

PMID- 14650381
TI  - Administering an enema to an adult.

PMID- 14650382
TI  - Flying blind with decorative lenses.

PMID- 14650383
TI  - Mycobacterium tuberculosis.

PMID- 14650384
TI  - Proceedings of the 2nd International Workshop on Gallbladder Motility. Ferrara,
      Italy, 14 October 2001.

PMID- 14650385
TI  - Stress myocardial perfusion imaging in the diagnosis and prognosis of women with
      suspected coronary artery disease.
AB  - Coronary artery disease is the single largest killer of women in the United
      States and claims the lives of more than 250,000 women each year. For several
      decades, there was the misperception that coronary artery disease was a "man's
      disease." The fact is that women are indeed vulnerable to coronary artery
      disease; however, they typically develop the disease 10 to 15 years later than
      men. Once coronary artery disease is evident, women have worse outcomes as
      compared with men.Therefore, early and accurate diagnosis of coronary artery
      disease is crucial for reducing heart disease mortality in women. Stress
      myocardial perfusion imaging using contemporary techniques has been shown to have
      significant value in the diagnosis and prognosis of coronary artery disease in
      women. Myocardial perfusion imaging with exercise or pharmacologic stress has
      been shown to add incremental value to the use of clinical variables or exercise
      electrocardiogram stress testing alone in the risk stratification of women with
      an intermediate clinical pretest likelihood of coronary artery disease. This
      review provides an overview of the role of stress myocardial perfusion imaging in
      the clinical evaluation of women with suspected coronary artery disease.

PMID- 14650386
TI  - Activated charcoal use.

PMID- 14650387
TI  - Shedding light on problem areas.

PMID- 14650388
TI  - An analysis of empirical research on the scope of justice.
AB  - The scope of justice has been defined as the boundary within which justice is
      perceived to be relevant. The empirical literature on this topic is primarily
      aimed at predicting when a target will be excluded from the scope of justice and
      at examining potential consequences of exclusion, from accepting a target's
      suffering to active harm-doing such as mass internment and genocide. The concept
      of the scope of justice is interesting and heuristically useful, but there are
      several problems with the empirical literature that impede its progress. For
      example, the proposed mediator often has not been measured, or
      operationalizations of the scope of justice have been confounded with other
      constructs. Also, although the scope of justice remains one possible explanation
      for results obtained in various experiments, there are equally compelling
      alternatives that do not implicate exclusion from the scope of justice. We offer
      suggestions about how to study scope of justice issues in the future and identify
      points that need to be clarified regarding the conceptualization of the scope of
      justice.

PMID- 14650390
TI  - Liquid chromatography problem solving and troubleshooting.

PMID- 14650389
TI  - The psychology of compensatory and retributive justice.
AB  - How do observers respond when the actions of one individual inflict harm on
      another? The primary reaction to carelessly inflicted harm is to seek
      restitution; the offender is judged to owe compensation to the harmed individual.
      The primary reaction to harm inflicted intentionally is moral outrage producing a
      desire for retribution; the harm-doer must be punished. Reckless conduct, an
      intermediate case, provokes reactions that involve elements of both careless and
      intentional harm. The moral outrage felt by those who witness transgressions is a
      product of both cognitive interpretations of the event and emotional reactions to
      it. Theory about the exact nature of the emotional reactions is considered, along
      with suggestions for directions for future research.

PMID- 14650391
TI  - Abstracts of the American Society of Hematology 45th Annual Meeting. December 6
      9, 2003. San Diego, California, USA.

PMID- 14650392
TI  - Abstracts of the American Society of Hematology 45th Annual Meeting. December 6
      9, 2003. San Diego, California, USA.

PMID- 14650393
TI  - [Stimulation measures mean professional boost for physicians in remote areas].

PMID- 14650394
TI  - Abstracts of the X International Workshop on CLL. 10-12 October 2003, Stresa,
      Lake Maggiore, Italy.

PMID- 14650395
TI  - Genetics, behaviour and psychiatry: historical burdens and perspective.
AB  - Familiar, twin, adoption and linkage studies represent the usual tools for
      assessing the possible role of genetics in mental disease. These genetic
      approaches have been refined in the last years and a number of methodological
      problems are absent in recent approaches. While there is no doubt that
      schizophrenia, mood disorders and autism are characterized by a genetic component
      no linkage study has been successful up to date, apart, probably, the case of
      autism. The existence of a genetic component does not minimize the role of the
      environment and of critical life events. It is also evident that no major genes
      are responsible for these psychiatric diseases: thus, quantitative trait loci
      analyses might prove fruitful in future research to track the role of different
      genes contributing to the outcome of different psychopathologies. The main
      problem, however, is the difficulty of carrying out quantitative analyses since
      the today's diagnostic tools do not allow a quantitative approach to these
      phenotypes.

PMID- 14650396
TI  - Abstracts of the 22nd Annual Scientific Meeting of the American Pain Society.
      March 20-23, 2003.

PMID- 14650397
TI  - Genetics and biotechnology in medicine historical, ethical, legal and social
      issues.

PMID- 14650398
TI  - From pharmacogenetics and ecogenetics to pharmacogenomics.
AB  - The origin and development of pharmacogenetics are traced with emphasis on early
      hints by Garrod, Haldane, and later by RJ Williams. The field was delineated by
      Motulsky in 1957 and described as pharmacogenetics by Vogel in 1959. Kalow's
      monograph (1962) definitely established the discipline. Resemblance of identical
      twins in drug metabolism as compared with non identical twins (Vesell, 1970's)
      established the general importance of polygenic inheritance in disposal of many
      drugs. Ecogenetics was defined by Brewer in 1971 as dealing with genetic
      variation affecting the response to any environmental agents with emphasis on
      xenobiotics. More recent developments have broadened pharmacogenetic approaches
      to include novel genomic techniques with introduction of the term
      pharmacogenomics in the 1990's. Genetic and genomic approaches (toxicogenetics
      and toxicogenomics) are also being applied in the "environmental genome project".
      The interaction of genetic variation with dietary factors led to the field of
      Nutritional ecogenetics (Nutrigenomics) which relates the role of genetics to
      nutritional requirements and nutrition-mediated susceptibility to chronic
      disease. The total promise of pharmacogenomics is often overstated. The field is
      likely to have an impact on choice of drug therapy and avoidance of adverse
      events but is unlikely to lead to a revolution in therapeutics. Aspects of
      pharmacogenomic approaches and its applications including problems of premature
      commercialization are discussed.

PMID- 14650399
TI  - Abstracts of the 4th SIAMOC Congress. 22-25 October 2003, Catania, Italy.

PMID- 14650400
TI  - Medical genetics to genomic medicine.
AB  - The essay analyses the conceptual and methodological implication of genetics and
      genomics as applied to medicine. Genomic medicine calls attention to the genome
      as the ultimate source of life's continuity and variety; and indicates at the
      least the origin of disease in molecular and genetic variation, and at the most,
      the role of the genes in all variation, including disease. While the literature
      of medical genetics, genomics, genomics and proteomics is energized by a keen
      anticipation of discovery most physicians are still thinking to the genes as
      merely another proximate cause. To them the thought that functional genomics and
      genetics are at the heart of life, is needed, based on a more evolutionary
      oriented views which recognize the individuality and heterogeneity of disease,
      the continuity of disease expression at the clinical level, and the multiplicity
      and integration of pathogenetic processes.

PMID- 14650401
TI  - The revolutionary implications of the word biotechnology.
AB  - Despite the success of the chemical industry, since the early 20th century
      biotechnology has been framed as a natural and revolutionary alternative. The
      idea has involved the interweaving of the concepts of engineering new products
      using living processes, and of engineering new living beings themselves. The
      potential of these twin themes as alternatives to chemical technologies has been
      debated since the revolutionary era at the end of World War I. Highpoints
      included the 1930s and the 1960s. The emergence of genetic engineering techniques
      in the 1970s enabled the realisation of long-existing aspirations. Ever since
      then there have been marked changes as the emphasis of biotechnology has shifted
      from the engineering of micro-organisms to produce proteins to the engineering of
      animals and even man. The sense of millenial change expressed when the human
      genome was first drafted is therefore both genuine and old-established.

PMID- 14650402
TI  - Lessons from anti-thalassemia campaigns in Italy, before prenatal diagnosis.
AB  - The essay reconstructs the antithalassemia campaign carried out by means of
      population screening and pre-marriage counseling for about twenty years in Italy,
      immediately after the relationship between microcythemia and Cooley's anemia had
      been established, as well as its genetic bases. We examine the Italian
      contributions to the understanding of the genetics and of the clinical treatment
      of thalassemic disorders, and analyze the approaches to prevention as well as the
      results obtained by the first campaign against a genetic disease, conceived and
      largely implemented in Italy by Ezio Silvestroni and Ida Bianco. We discuss the
      resistances met by the antithalassemia campaign due to the cultural and
      organizational backwardness of the Italian medical community and of the public
      health system. Moreover we analyze the explanations and interpretations of the
      problematic results of these experiences in terms of morbidity reduction. It will
      be pointed out that the objective of genetic counselling practised in that
      context assumed the concept of disease prevention at the population level, and it
      was far from the idea, emerged in the 1970s, of non directive genetic
      counselling.

PMID- 14650403
TI  - Contested conceptions: PKU in the postwar discourse on reproduction.
AB  - This essay uses the case of PKU as a portal through which to view shifting and
      contested views about genetics and reproductive behavior. In the early 1960s, the
      development of an effective therapy for PKU converged with the development of a
      test that could reliably detect the condition in newborns. As a result, infants
      born with the condition were enabled to reach adulthood and reproduce. However,
      by the early 1980s, a "second-generation" effect of screening was manifest,
      whereby many infants born to women who had been salvaged by screening were
      themselves severely damaged. In the 1940s, Lionel Penrose employed the case of
      PKU to demonstrate what was wrong with eugenics. Twenty years later, it would be
      used to illustrate why controls on reproduction were needed.

PMID- 14650404
TI  - Historical aspects of genetic counseling: why was maternal age 35 chosen as the
      cut-off for offering amniocentesis?
AB  - The justification for offering amniocentesis to women age 35 or older is that by
      age 35 the risk of having a child with chromosome problem is greater than the
      risk of amniocentesis. In fact, this seemingly objective statement is not
      supported by historical analysis. Maternal age 35 was chosen for the cutoff based
      mostly on economic cost-benefit analysis rather than objective medical
      assessment. The story of why 35 was chosen illustrates how collective memory can
      affect, and be influenced by, the guiding ethical principles of a medical
      profession.

PMID- 14650405
TI  - Leprosy and the elusive M. leprae: colonial and Imperial medical exchanges in the
      nineteenth century.
AB  - In the 1800s, humoral understandings of leprosy successively give way to disease
      models based on morbid anatomy, physiopathology, and bacteriology. Linkages
      between these disease models were reinforced by the ubiquitous seed/soil metaphor
      deployed both before and after the identification of M.leprae. While this
      metaphor provided a continuous link between medical descriptions, Henry Vandyke
      Carter's On leprosy (1874) marks a convergence of different models of disease.
      Simultaneously, this metaphor can be traced in popular medical debates in the
      late nineteenth century, accompanying fears of a resurgence of leprosy in Europe.
      Later the mapping of the genome ushers in a new model of disease but, ironically,
      while leprosy research draws its logic from a view of the world in which a seed
      and soil metaphor expresses many different aspects of the activity of the
      disease, the bacillus itself continues to be unreceptive to cultivation.

PMID- 14650406
TI  - Social representation of Hansen's disease thirty years after the term "leprosy"
      was replaced in Brazil.
AB  - Based on the theories of social representation (SC) and Central Core (CC), a
      structural study was undertaken regarding the neologism hanseniase (Hansen's
      disease), the term adopted by Brazil's Ministry of Health in the 1970s. Carried
      out during 2001, this study interviewed eight hundred housewives residing in the
      Rio de Janeiro and Duque de Caxias municipalities. It found that Hansen's disease
      is part of a process of modernization of common thinking, anchored in the
      additional representation of leprosy. This finding is understandable from the
      perspective that the central structure of a social representation has a
      historical determination, so short -and middle-term changes are not to be
      expected. Furthermore, there has been no ongoing investment in social marketing
      to make the new terminology more widely known. The authors discuss the relation
      between social representation and the concept of the history of mentalities.

PMID- 14650407
TI  - Adolpho Lutz and controversies over the transmission of leprosy by mosquitoes.
AB  - During his years of study in Switzerland and Germany, Adolpho Lutz published his
      first articles on zoology, clinical practice, and therapeutics. In Limeira, Sao
      Paulo, he began studies on animal and human diseases caused by germs and
      parasites. In 1885-86, Lutz traveled to Hamburg to study the morphology of germs
      related to skin diseases, in conjunction with Paul Gerson Unna, one of Germany's
      foremost dermatologists. He proposed the inclusion of Hansen's and Koch's bacilli
      in a new genus. In 1889, Unna nominated his student as physician-in-chief of the
      Leper Settlement on Molokai Island, Hawaii. From then on, Lutz sustained the
      theory that the disease was transmitted by mosquitos. He conducted research to
      prove this theory when he was head of the Instituto Bacteriologico de Sao Paulo
      (1893-1908) and, later, after he moved to the Instituto Oswaldo Cruz (1908-1940).
      Although this research was not successful, on commissions and at congresses in
      which he participated until his death in October 1940, he still held to his
      conviction that leprosy was transmitted by mosquitoes.

PMID- 14650408
TI  - Prophylaxis and exclusion: compulsory isolation of Hansen's disease patients in
      Sao Paulo.
AB  - This article aims to retrieve the history of Hansen's disease in Brazil,
      analyzing the medical thinking of the time and the shaping of health policies
      that permitted the implementation, in Sao Paulo, of a prophylactic policy of
      compulsory exclusion for all Hansen's disease patients. It also analyzes how the
      structuring and implementation of this policy led to a "Sao paulo model" that
      strongly influenced the rest of the country. It addresses the creation of the
      state's network of leper colonies, their characteristics and the emergence of a
      veritable "parallel state" that endured until 1967, with complete disregard of
      all the changes taking place in both national and international prophylactic
      policymaking.

PMID- 14650409
TI  - Carville and Curupaiti: experiences of confinement and community.
AB  - Although Hansen's disease (leprosy) is still a significant problem in many parts
      of the world, the effectiveness of multidrug therapy has allowed people affected
      by this disease to be treated on an outpatient basis. However, throughout much of
      the twentieth century, people diagnosed with Hansen's disease were isolated from
      their families in facilities known as "leprosaria". This article presents a brief
      history of isolation policies and the development of community structures at two
      such facilities, Carville and Curupaiti, in the United States and Brazil,
      respectively. The modern dilemmas faced by the administration, staff, and
      residents of these institutions will also be discussed.

PMID- 14650410
TI  - A monument to Lazarus: the leprosy hospital of Rio de Janeiro.
AB  - Soon after the Portuguese made landfall in 1500, Europeans and, later, African
      slaves introduced leprosy, and Saint Lazarus, the patron saint of its victims,
      into Brazil. Social and political pressure mounted by the middle of the
      eighteenth century in the city of Rio de Janeiro to remove those unfortunates
      from the city's streets even before the move of Brazil's capital in 1763. Frei
      Antoniom the bishop of Rio, founded the venerable hospital that year in the
      neighborhood of Sao Cristovao, He requested that the Irmandade do Santissimo
      Sacramento da Candelaria provide oversight and administration. The brotherhood
      continues to honor its covenant of 239 years ago. The history of this hospital
      provides insight into the complex relationships that existed between the
      citizenry and church and state. Rio's leprosy hospital, now the Hospital Frei
      Antonio, had an important role in the evolution of the health care professions,
      progress in medical science, and the genesis of the hygienic movement in Brazil.
      This study also contributes to the history of a disease that persists in 2002
      Brazil as a public health issue.

PMID- 14650411
TI  - Management of severely calcified right coronary artery.

PMID- 14650412
TI  - The first international leprosy conference, Berlin, 1897: the politics of
      segregation.
AB  - The present paper examines the first attempts to internationalize the problem of
      leprosy, a subject hitherto overlooked by historians of imperialism and disease.
      The last decade of the nineteenth century saw many in the 'civilized countries'
      of the imperialist West gripped by a paranoia about an invasion of leprosy via
      germ-laden immigrants and returning expatriates who had acquired the infection in
      leprosy-endemic colonial possessions. Such alarmists clamoured for the adoption
      of vigorous leper segregation policies in such colonies. But the contagiousness
      of leprosy did not go unquestioned by other westerners. The convocation in Berlin
      of the first international meeting on leprosy revealed the interplay of differing
      and sometimes incompatible views about the containment of leprosy by segregation.
      The roles of officials from several countries, as well as the roles of five
      protagonists (Albert Ashmead, Jules Goldschmidt, Edvard Ehlers, Armauer Hansen,
      and Phineas Abraham) in the shaping of the Berlin Conference are here examined.

PMID- 14650413
TI  - The anti-leprosy campaign in Colombia: the rhetoric of hygiene and science, 1920
      1940.
AB  - Since the 1920s, the medical community realized that the strategy of leprosy
      control based on segregation and persecution of patients was inefficient and
      expensive. In the 1930s the new liberal government incorporated leprosy within
      the general sanitary institutions, by merging the Bureau of Lazarettos and the
      National Department of Hygiene. The disease-apart approach started to be replaced
      by a more general public health strategy, which involved controlling other
      illnesses. Prevention and research played a more influential role, and the new
      sanitary officials saw leprosy in the light of the economic rationality of
      expenditures, placing more emphasis on therapies and making them mandatory for
      all patients. Improvements in leprosy treatment became widely known and
      available. However, the image of leprosy as a special condition and the practice
      of segregation were deeply entrenched within the Colombian culture and
      institutions. The rhetoric changed, but to break with several decades of
      persecution was a difficult task.

PMID- 14650415
TI  - Beyond quarantine: a history of leprosy in Puerto Rico, 1898-1930s.
AB  - From biblical times to the modern period, leprosy has been a disease associated
      with stigma. This mark of disgrace, physically present in the sufferers' sores
      and disfigured limbs, and embodied in the identity of a "leper", has cast leprosy
      into the shadows of society. This paper draws on primary sources, written in
      Spanish, to reconstruct the social history of leprosy in Puerto Rico when the
      United States annexed this island in 1898. The public health policies that
      developed over the period of 1898 to the 1930s were unique to Puerto Rico because
      of the interplay between political events, scientific developments and popular
      concerns. Puerto Rico was influenced by the United States' priorities for public
      health, and the leprosy control policies that developed were superimposed on
      vestiges of the colonial Spanish public health system. During the United States'
      initial occupation, extreme segregation sacrificed the individual rights and
      liberties of these patients for the benefit of society. The lives of these
      leprosy sufferers were irrevocably changed as a result.

PMID- 14650414
TI  - Global and local contexts: the Northern Ogoja Leprosy Scheme, Nigeria, 1945-1960.
AB  - Deriving funding from missionary sources in Ireland, Britain and the USA, and
      from international leprosy relief organizations such as the British Empire
      Leprosy Relief Association (BELRA) and drawing on developing capacities in
      international public health under the auspices of WHO and UNICEF through the
      1950s, the Roman Catholic Mission Ogoja Leprosy Scheme applied international
      expertise at a local level with ever-increasing success and coverage. This paper
      supplements the presentation of a successful leprosy control program in
      missionary narratives with an appreciation of how international medical politics
      shaped the parameters of success and the development of therapeutic understanding
      in the late colonial period in Nigeria.

PMID- 14650416
TI  - "Essentially Christian, eminently philanthropic": the Mission to Lepers in
      British India.
AB  - The early history of the Mission to Lepers in India is an interplay between
      politics, religion, and medicine in the context of British imperialism. The
      Mission pursued the dual but inseparable goals of evangelization and
      civilization, advancing not only a religious program but also a political and
      cultural one. These activities and their consequences were multi-faceted because
      while the missionaries pursued their religious calling, they also provided
      medical care to people and in places that the colonial government was unable or
      unwilling. Within the context of the British imperial program, the work imparted
      Western social and cultural ideals on the colonial populations they served,
      inculcated patients with Christian beliefs, and provided medical care to
      individuals who had been expelled from their own communities. Physical healing
      was intimately tied to religious salvation, spiritual healing, and the civilizing
      process.

PMID- 14650417
TI  - [Hansen's disease in the laboratory].
AB  - A physical doctor with a PhD in Pathology, Euzenir Nunes Sarno studies the
      immunology factors of Hansen's disease, one of the oldest chronic infections and
      that is an exclusively human disease. Staff member of an ambulatory that has
      become a reference on the disease in Brazil with 220 to 250 new patients per
      year, Euzenir emphasizes that the fact one cannot cultivate Mycobacterium leprae
      brings about some everlasting questions in relation to the transmission of and
      the sensitivity to the disease. There are also many epidemiology questions that
      remain unanswered. Estimates show that, among those who have contact with multi
      bacilli patients, 90% are infected but only about 8% get sick. The high infection
      rate of those who live with multi-bacilli patients but never fall sick shows that
      just a small number of individuals are sensitive to Mycobacterium leprae. This is
      one of the questions immunology has not been able to answer. Why do some people
      resist to it and some don't? The figures are even lower when compared to those
      who are in contact with patients that are paucibacillus-infected, i.e. a
      manifestation of the disease with few bacilli. Hansen's disease is known as a
      skin malady. But, according to the specialist, its first damage is to the nerve,
      when the area becomes insensitive. Besides damaging the sensitive skin nerves,
      the disease can lead to motor disability and irreversible deformities, which
      sometimes lead to the amputation of limbs and protruded parts of the body.
      Mycobacterium leprae was one of the first pathogenic bacteria whose genome
      sequence has been entirely mapped. Only now we have the capacity to have more
      precise assessments. The disease is not inherited, and only in 1986 health
      services in Brazil began to take the responsibility for both the disease and its
      patients. During the twenty-year military dictatorship the country underwent, the
      health system was dismantled. In 1991, the one-year treatment with three drugs -
      Dapsone, Rifanpicine and Clofazimine- was introduced in our country. Just 30% of
      the cases get to negative results after the treatment. according to the
      interviewee, whereas tuberculosis is a highly virulent multi-bacilli disease,
      leprosy bacillus is not virulent, is a 'lazy' germ at the end of its evolutional
      process. One third of its genome does not work.

PMID- 14650418
TI  - [A panorama of Hansen's disease: present status and perspectives].
AB  - The interviewee speaks about the endemic disease, which at present contaminates
      4.4 out of ten thousand inhabitants in Brazil, the country with the second
      highest number of patients. When Tadiana speaks about the Brazilian participation
      in the program launched by the World Health Organization, she explains that WHO's
      objective is to extinguish Hansen's disease on the planet until 2005. However,
      she says that Brazilian main goal is to reduce the occurrence of the disease to
      less than one case per ten thousand people. In our country, the structure and the
      organization of this program, which comprehends the education and specialization
      of professionals in order to guarantee early diagnoses, as well as patients'
      follow-up during treatment, is developed by Sistema Unico de Saude (SUS) and has
      been implemented in all the states of the federation. The chemotherapy treatment
      lasts about a year, when taken seriously. In many cases, the disease comes back a
      while later. Tadiana comments on the differences of the disease according to the
      different regions of the country. It has been extinguished in the South,whereas
      the rates in the North and Central East regions almost reach endemic peaks.
      Working close to patients and ex-patients associations, first as a nurse and
      later in the implementation of policies for Hansen's disease issues, Tadiana
      Alves Moreira stresses the importance of early diagnoses, which avoid the
      physical damages and deformities that take place in the advanced stages of the
      disease, so reducing the stigma over the diseased.

PMID- 14650419
TI  - Bilateral pneumonia associated with Shigella sonnei dysentery.

PMID- 14650420
TI  - Hospital- or health care establishments-acquired infection and quality and
      bioavailability of antimicrobial agents.

PMID- 14650421
TI  - Memories and history of Hansen's disease in Brazil told by witnesses (1960-2000).
AB  - This report is a preliminary result of a survey on memories and history of
      Hansen's disease, or 'hanseniasis', prepared by the Fundacao Oswaldo Cruz
      (Fiocruz) and the Universidade Federal do Rio de Janeiro (UFRJ) using statements
      from those who have been afflicted by the disease or those that have fought
      against it. It outlines the methodology used by the authors and gives a succinct
      history of Hansen's disease in Brazil, together wish information on the stage of
      the survey with extracts from our archives of statements. The founding and the
      role of Movement for the Reintegration of People Afflicted by Hansen's Disease
      (Morhan) are explained in the testimony of Thomas Frist, a social scientist who
      worked in Brazil in the 1970s and 1980s, when the country's old colonies were
      being restructured, and Cristiano Torres, a former patient who spent time in
      prevention centers and leproseries in Para state and who is now active in
      proposing new policy for the control of Hansen's disease.

PMID- 14650422
TI  - [Diagnosis and antimicrobial treatment of sinusitis].

PMID- 14650423
TI  - Vida de leprosa: the testimony of a woman living with Hansen's disease in the
      Peruvian Amazon, 1947.
AB  - This is the narrative of a patient made before, during and after being
      incarcerated in an agricultural colony in the Peruvian Amazon. In a vivid style,
      it narrates the decay of the body, the stigma and the compulsive segregation, as
      well as the hope for a better life. It is the perspective of a patient, something
      that is difficult to find when researching the history of health. The original
      publication was possible thanks to the German physician Maxime H. Kuczynski
      Godard and thanks to the Institute of Social Medicine of the University of San
      Marcos that was directed by the professor of hygiene Carlos Enrique Paz-Soldan.
      We have used this publication for this transcription. Kuczynski-Godard was a
      German medical doctor that arrived in Peru in the mid 1930s and organized
      valuable activities in the Peruvian jungle as a part of an effort, which
      eventually failed, of the Peruvian State to colonize, or really to "civilize" the
      Amazon.

PMID- 14650424
TI  - Fight for survival: the life of a Hansen's disease sufferer through his
      correspondence with Adolpho Lutz.
AB  - This project presents the complete set of letters between the family of a
      Hansen's disease (leprosy) sufferer in the state of Maranhao, in the Northeast of
      Brazil, and the doctor and bacteriologist Adolpho Lutz. For more than twenty
      years Fabricio Caldas de Oliveira and Numa Pires de Oliveira, father and son,
      exchanged a steady flow of letters with the scientist in pursuit of a cure for
      the disease that had assailed Numa since childhood. The 24 letters compiled here
      paint a unique portrait of the medical and social drama confronted by this
      family, and the results of the use of chaulmoogra oil and other medications in
      their search for alternative treatments.

PMID- 14650425
TI  - [Revealing a history of exclusion: the experience at Hospital-Colonia Itapua Data
      and Research center].
AB  - Inaugurated in May 1940, in Viamao Municipality in Rio Grande do Sul, Hospital
      Colonia Itapua was meant to shelter Hansen's disease patients. Built in order to
      work as a small town, the hospital was the stage of several life and work
      histories. The fragments of these collective and individual experiences have been
      recovered since 1999, when Centro de Documentacao e Pesquisa (Cedope/HCI) was
      first implemented. It is through the center activities that we propose a
      comparative study of the history of the hospital and the history of those who
      lived and those who still live in it.

PMID- 14650426
TI  - [Researching documents on the history of hansen's disease in Brazil].
AB  - This article corresponds to part of the results of a research on leprosy-related
      sources developed in several institutions in the city of Rio de Janeiro. At Real
      Gabinete Portugues de Leitura, Arquivo Nacional and Biblioteca Nacional, banks,
      indexes, official documents and photos on the administration of leprosaria and
      articles on the treatment of the disease have been investigated. At Centro de
      Pesquisa e Documentacao de Historia Contemporanea do Brazil (CPDOC-FGV), several
      files have been researched, mainly those with information on the health policies
      of the first Vargas administration (1930-1945). This research is part of the
      International Leprosy Association Global Project on the History of Leprosy. Its
      results can be accessed at the site http://www.leprosyhistory.org

PMID- 14650427
TI  - The papers of Stanley Browne: leprologist and medical missionary (1907-1986).
AB  - This article elaborates a significant archival acquisition that supplement the
      collection documents related to the life and work of Stanley George Browne held
      at the Wellcome Library for the History and Understanding of Medicine in London,
      specifically his work in the Belgian Congo (from 1936 to 1959), at Uzuakoli in
      Nigeria (1959 to 1966), in London with the Leprosy Study Centre (1966-1980), and
      also in his international capacity as leprosy consultant. It also briefly refers
      to an endangered collection of documents, photographs, files and correspondence
      held in a small museum in Culion Sanatorium, The Philippines. This research is
      part of the International Leprosy Association Global Project on the History of
      Leprosy. Its results can be accessed at the site http://www.leprosyhistory.org

PMID- 14650428
TI  - Claude M. Steele: Award for Distinguished Scientific Contributions.

PMID- 14650429
TI  - Cardiac surgery in Germany during 2002: a report by German Society for Thoracic
      and Cardiovascular Surgery.

PMID- 14650430
TI  - Sps-3 transcript levels are determined by multiple remote sequence elements.
AB  - The region from 1.4 to 2.7 kb upstream of Drosophila melanogaster gene Sgs-3 is
      responsible for a 10-fold increase in Sgs-3 transcript levels in the third instar
      larval salivary gland. This region includes the related Sgs-7 gene from the 68C
      glue gene cluster as well as 400 bp of its 5' sequences. We show that two
      elements are involved, each contributing a modest 3-fold effect. One of these
      includes Sgs-7 transcribed sequences some 2.3 kb upstream of Sgs-3, although Sgs
      7 transcription is not involved. Although important for the overall levels of Sgs
      3 expression, they are clearly not strong, viral-like enhancer elements. We
      propose that many position effects observed in P element transformation studies
      are the consequence of insertion in the vicinity of similar elements dispersed
      throughout the genome and having modest effects on transcript levels.

PMID- 14650431
TI  - The instability of the TE-like mutation Dp(2:2)GYL of Drosophila melanogaster is
      intimately associated with the hobo element.
AB  - We have characterized molecularly several derivatives of the TE-like element
      Dp(2:2)GYL of Drosophila melanogaster. This highly unstable mutation occurred in
      a dysgenic cross involving the 23.5 MRF chromosome, and represents an inverted
      insertional duplication of approximately 130 polytene bands of the paternal 2L,
      at 50AB of the right arm of the maternal 2R. The instability of this mutation is
      characterized by deletion of some of duplicated material, by the induction of
      rearrangements in its vicinity and by the transposition of parts of the original
      element. We have found that the mobile element hobo is present at , or very near,
      the breakpoints of all GYL derivatives analysed, demonstrating that hobo is not
      only active in dysgenic crosses, but also that it can promote genetic instability
      reminiscent of transposable elements (TE).

PMID- 14650432
TI  - Double and triple mutant combinations of bithorax complex of Drosophila.
AB  - We have constructed double and triple mutant combinations for the Ubx, abd-A and
      Abd-B genes of the bithorax complex and have examined the homeotic
      transformations they produce in the larval and adult patterns. Embryos hemizygous
      for the triple combination exhibit a metameric pattern consisting of parasegments
      5-12 being transformed into parasegment 4. In addition, parasegment 13 develops
      like a mixture of parasegment 3 and 4, and parasegment 14 is abnormal. The same
      phenotype is displayed by embryos homozygous for DfP9, lacking all the BX-C DNA,
      >300 kb. This result strongly supports the notion that the BX-C contains only
      three genes which account for all the developmental functions of the complex. The
      phenotypes of the different double combinations also support the same view; the
      Ubx abd-a comthoracic and several abdominal functions. The abd-A Abd-B
      combination exhibits the same phenotype of DpP10 DfP9, lacking all the abdominal
      functions except those specific for A1. Our results also indicate that each BX-C
      gene becomes active autonomously regardless of the presence or functional state
      of the other BX-C genes.

PMID- 14650433
TI  - Plastid, nuclear and reverse transcriptase sequences in the mitochondrial genome
      of Oenothera: is genetic information transferred between organelles via RNA?
AB  - We describe an open reading frame (ORF) with high homology to reverse
      transcriptase in the mitochondrial genome of Oenothera. This ORF displays all the
      characteristics of an active plant mitochondrial gene with a possible ribosome
      binding site and 39% T in the third codon position. It is located between a
      sequence fragment from the plastid genome and one of nuclear origin downstream
      from the gene encoding subunit 5 of the NADH dehydrogenase. The nuclear derived
      sequence consists of 528 nucleotides from the small ribosomal RNA and contains an
      expansion segment unique to nuclear rRNAs. The plastid sequence contains part of
      the ribosomal protein S4 and the complete tRNA(Ser). The observation that only
      transcribed sequences have been found i more than one subcellular compartment in
      higher plants suggests that interorganellar transfer of genetic information may
      occur via RNA and subsequent local reverse transcription and genomic integration.

PMID- 14650434
TI  - Combination of lamin immunocytochemistry and in situ hybridization for the
      analysis of chromosome copy numbers in tumor cell areas with high nuclear
      density.
AB  - We describe the application of lamin immunocytochemistry (ICC) and single- or
      double-target fluorescence in situ hybridization (FISH) on 4 microm thick frozen
      tissue sections as a method to facilitate scoring of aberrant chromosome copy
      numbers in colonic tumors. Analysis of FISH signals in colon tissue sections is
      often hampered by overlap and truncation of epithelial nuclei, due to the density
      of the epithelial cells. Furthermore, on the basis of nuclear staining it is
      often difficult to determine whether or not nuclei are overlapping, or adjoining.
      Therefore, reliable evaluation of (F)ISH signals to screen for genomic changes
      was until now mainly restricted to isolated nuclei obtained from relatively thick
      tissue sections. In this study the applicability of lamin ICC, to stain the
      nuclear periphery and to distinguish individual nuclei, combined with the FISH
      procedure is explored to solve this problem for colon epithelium. For ICC we
      applied the alkaline phosphatase (APase)-Fast Red detection method, since the
      fluorescent precipitate of this reaction resists extensive proteolytic digestion
      as needed for efficient FISH on tissue sections. Chromosome copy numbers could
      easily be determined in 4 microm thick frozen tissue sections by combining lamin
      ICC and FISH. The ratio of the copy numbers of the chromosomes 7 and 17 could be
      determined in frozen tissue sections after combined lamin ICC and double-target
      FISH. It is concluded that the combination of lamin ICC and FISH improves
      chromosome copy number analysis and can be used to investigate genomic changes in
      different tumor compartments in thin frozen tissue sections.

PMID- 14650435
TI  - Effect of chromatic errors in microscopy on the visualization of multi-color
      fluorescence in situ hybridization.
AB  - The relevant microscopical conditions for the optimal visualization of ratio
      color FISH stained cells were investigated. Special attention was given to the
      influence of the type of illumination, (semi)-critical vs. Kohler type
      illumination, in combination with the use of multi-band excitation and emission
      filters, on the registration of the colors of ratio labelled probes. Due to
      chromatic errors, many collecting lenses were found to cause a wavelength
      dependent excitation pattern with critical illumination. This resulted in a
      change of the observed color of microscopic objects when stained with a mixture
      of two dyes and excited with a dual band pass filter. A quantitative study of
      this effect for semi-critical illumination of FISH ratio-labelled chromosomes
      revealed a difference of 20% between highest and lowest ratio values depending on
      the position of the object in the microscopic field vs. only 2.5% for Kohler type
      of illumination. The impact of these errors on the identification of ratio
      labelled probes and on the sensitivity of comparative genomic hybridization (CGH)
      to detect gene amplifications or losses is discussed. Standard preparations
      consisting of solutions of defined mixtures of fluorescent dyes or objects
      stained with defined ratios of fluorophores, are proposed to correct for the
      errors observed.

PMID- 14650436
TI  - Largest contour segmentation: a tool for the localization of spots in confocal
      images.
AB  - An accurate determination of the 3-D positions of multiple spots in images
      obtained by confocal microscopy is essential for the investigation of the spatial
      distribution of specific components or processes in biological specimens. The
      position of the centroid, as an estimator for the position of a spot, can be
      calculated on the basis of all voxels that belong to the domain of the spot. For
      this calculation a domain that defines which voxels belong to the spot must be
      delimited. To create a boundary for a domain we developed a 3-D image
      segmentation procedure: the largest contour segmentation (LCS). This procedure is
      based on an iterative region-growing procedure around each local maximum of
      intensity. By means of this procedure the position of each spot was determined
      accurately and automatically. Qualities of the procedure were evaluated by means
      of simulated test-images as well as 3-D images of real biological specimens.

PMID- 14650437
TI  - Effects of pressure on red blood cell geometry during micropipette aspiration.
AB  - Micropipette aspiration is a potentially useful and accurate technique to measure
      red blood cell (RBC) geometry. Individual RBCs are partially aspirated and from
      the resulting sphere diameter, total cell length, and pipette diameter, membrane
      area and cell volume can be calculated. In this study we have focused on possible
      shape artifacts associated with the aspirated portion of RBC. We observed that
      the apparent RBC geometry (calculated area and volume) changed markedly (P <
      0.001) with the applied aspiration pressure; for normal human RBC the area
      increased by 5.6 +/- 0.6% and volume decreased by 4.7 +/- 0.6% when the
      aspiration pressure was increased from 20 to 100 mm water. The calculated
      membrane area dilation modulus was 7.4 dyn/ cm, which is far below the expected
      value, and microscopic observations revealed a membrane folding artifact as a
      possible artifact. These assumptions were strengthened by using a short-duration
      (3 s) pressure peak of 20-100-20 mm water. The folding then disappeared
      permanently, but a small (0.31 +/- 0.09%; P < 0.001) area decrease was detected
      which yields a realistic dilation modulus of 215 dyn/cm. We conclude that
      membrane folding can critically affect RBC micropipette measurements and that a
      transient pressure peak can unfold the RBC membrane, thus allowing accurate
      measurements of RBC geometry.

PMID- 14650438
TI  - Discrimination of respiratory dysfunction in yeast mutants by confocal
      microscopy, image, and flow cytometry.
AB  - Living yeast cells can be selectively stained with the lipophilic cationic
      cyanine dye DiOC6(3) in a mitochondrial membrane potential-dependent manner. Our
      study extends the use of flow cytometric analysis and sorting to DiOC6(3)-stained
      yeast cells. Experimental conditions were developed that prevented the toxic side
      effect of the probe and gave a quantitative correlation between fluorescence and
      mitochondrial membrane potential, without any staining of other membranes. The
      localization of the fluorochrome was checked by confocal microscopy and image
      cytometry. The mitochondrial membrane alterations were also tested through
      cardiolipin staining with nonyl acridine orange. Differences in light scattering
      and in fluorescence were detected in mutants (rho-, rho degrees, mit-, or pet-)
      and wild-type (rho+mit+) populations of yeast. The dye uptake of respiratory
      deficient yeast strains was significantly reduced as compared to that of the wild
      type. Application of an uncoupler (mCICCP), which collapsed the mitochondrial
      membrane potential (alphapsi(m)), led to a drastic reduction of the dye uptake.
      It was observed that a decrease in deltapsi(m), was usually correlated with a
      decrease in cardiolipin stainability by nonyl acridine orange (NAO). Quantitative
      flow cytometry is a fast and reproducible technique for rapid screening of yeast
      strains that might be suspected of respiratory dysfunction and/or mitochondrial
      structural changes. We give evidence that it is an adequate method to
      characterize and isolate respiratory mutants through sorting procedure, with
      selective enrichment of the population studied in respiring or non-respiring
      yeast cells. Confocal microscopy and image cytometry corroborate the flow
      cytometry results.

PMID- 14650439
TI  - Comparative analysis of CD4-mediated down-regulation of T cell adhesion to B
      cells by flow cytometry and fluorescence microscopy.
AB  - We have previously shown by means of fluorescence microscopy that antigen
      independent adhesion of resting CD4 T cells to EBV-transformed B cells can be
      down-regulated by ligand interaction with CD4. In this study we used flow
      cytometry analysis of conjugate formation to confirm these findings. No
      conjugates between resting CD4 + T cells and B cells were initially detected in
      the latter method, because flow velocity in the flow chamber induces hydrodynamic
      elongation forces which disrupt low-affinity conjugates. After forcing cell
      conjugation by low-speed centrifugation of T and B cells, conjugates became
      detectable although in smaller numbers than in fluorescence microscopy. "Forced"
      cell conjugates had similar characteristics to their unforced counterparts, i.e.,
      37 degrees C temperature dependency, mediation by LFA-1/ICAM-1 and CD2/LFA-3
      pathways, and transiency. The latter characteristic was at least partly mediated
      by CD4/HLA class II interaction, since adhesion of CD4 + T cells to HLA class II
      B cells was more stable. In addition, adhesion was inhibited by anti-CD4
      antibodies but not by an HLA DR-derived peptide known to inhibit unforced CD4 + T
      cell adhesion to B cells. This blocking effect was partially reproduced by
      reducing the centrifugation time prior to the adhesion assay. These results show
      that a) CD4-mediated down-regulation of T cell adhesion can be observed by means
      of two different techniques, and b) analysis of cell-cell adhesion after
      increasing centrifugation times (and possibly speeds) is a simple way of
      measuring adhesion forces semiquantitatively.

PMID- 14650440
TI  - Immunofluorescence signal amplification by the enzyme-catalyzed deposition of a
      fluorescent reporter substrate (CARD).
AB  - Progress has been made in improving the immunohistochemical detection of antigens
      for imaging and flow cytometry. We report the synthesis of a novel fluorescent
      horseradish peroxidase substrate, Cy3.29-tyramide, and its application in an
      enzyme-based signal amplification system, catalyzed reporter deposition (CARD).
      The catalyzed deposition of Cy3.29-tyramide was used to detect cell surface
      markers such as CD8 and CD25 on tonsil tissue and human lymphocytes. We compared
      the fluorescence CARD method to standard indirect immunofluorescence detection
      methods and found that an amplification of up to 15-fold was possible with CARD.
      The detection of the intracellular protein myosin II in fibroblastic cells and
      rabbit serum proteins blotted onto nitrocellulose was also improved. Thus,
      fluorescent CARD is a simple modification that can be made to standard
      immunofluorescence staining protocols to enhance significantly the detection of
      antigens.

PMID- 14650441
TI  - Identification of a human erythroid progenitor cell population which expresses
      the CD34 antigen and binds the plant lectin Ulex europaeus I.
AB  - Two and three color flow cytometry of normal human bone marrow was used to
      identify CD34+ progenitor cells and examine their binding to the plant lectin
      Ulex europaeus I (Ulex). In normal bone marrow, 48.48 +/- 17.4% of the CD34+
      cells bind to Ulex. Two color flow cytometry was used to sort CD34 + cells, and
      subsets of CD34+ cells, CD34+ Ulex+ and CD34+ Ulex-. These populations were
      sorted into colony assays to assess myeloid (CFU-GM) and erythroid (BFU-E)
      progenitors. The CD34+ Ulex+ subset was 84 +/- 14% BFU-E colonies (mean +/- S.D.)
      and had the highest cloning efficiency of 28 +/- 13%. Three color analysis of
      CD34+ Ulex+ cells showed staining with other erythroid (CD71, GlyA) antibodies
      and lack of stain. ing with myeloid (CD13, CD45RA) antibodies. These studies
      confirmed the erythroid characteristics of this subpopulation.

PMID- 14650442
TI  - Analysis of heparin binding to human leukocytes using a fluorescein-5
      isothiocyanate labeled heparin fragment.
AB  - The binding of LMWH-tyr-FITC to granulocytes, monocytes, and lymphocytes was
      analyzed by flow cytometry using a low-molecular-weight heparin (LMWH) labeled
      with fluorescein-5-isothiocyanate (FITC). FITC was covalently bound to tyramine,
      which was synthesized to LMWH by endpoint-attachment (Malsch et al.: Anal Biochem
      217:255-264, 1994). The binding was rapid, specific, dose-dependent, saturable,
      and reversible. To investigate the molecular weight dependence of heparins,
      heparin-derived di- to dodecasaccharides were used. With decreasing molecular
      weight, the amount of oligosaccharides increased; these were bound to
      granulocytes, monocytes, and lymphocytes (r = -0.77). The degree of sulfation of
      non-heparin glycosaminoglycans influenced the binding to leukocytes. Decreasing
      the degree of sulfation decreased the binding. The pentasaccharide did not bind
      as strongly as the other heparin-derived oligosaccharides, indicating an AT III
      independent mechanism. Two classes of heparin binding sites were identified on
      granulocytes and one class of binding sites on monocytes and lymphocytes. The
      lowest amount of LMWH-tyr-FITC detected was 1 ng on granulocytes, 0.18 ng on
      monocytes and 0.01 ng on lymphocytes. The data suggest that heparin and other
      sulfated polysaccharides may play a role in the physiology of thrombosis,
      arteriosclerosis, and inflammation by binding to granulocytes, monocytes, and
      lymphocytes.

PMID- 14650443
TI  - Third-color CD45 staining of paraformaldehyde-fixed peripheral blood lymphocytes.
AB  - Third-color CD45 gating is a useful procedure in various clinical applications
      (Borowitz et al.: Am J Clin Pathol 100:534-540, 1993; Steltzer et al.: Ann NY
      Acad Sci 677:267-280, 1993) allowing for the selective immunophenotyping of
      abnormal cell populations. In laboratories where dual-color protocols are in
      place, the need for CD45 gating may not become evident until after cells have
      been exposed to fixatives. This brief study demonstrates that third-color CD45
      staining and gating is possible with paraformaldehyde fixed lymphocytes,
      eliminating the need to restain fresh cells with the entire antibody panel, and
      with a significant saving of time and money. Gates must be modified from those
      obtained by fresh cell staining in order to include both bright and dim CD45
      populations. In a standard protocol, third-color CD45 staining intensity was
      decreased 10-fold post-fixation with paraformaldehyde except, unexpectedly, for
      CD8+ cells. The latter phenomenon could be explained if the spatial arrangement
      of CD45 and CD8 is such that the CD45 epitope is protected from cross-linking by
      paraformaldehyde fixation in CD8+ cells, but not others.

PMID- 14650444
TI  - Use of a lectin as an enterocyte-specific cell surface marker for flow cytometric
      analysis of isolated native small intestinal epithelial cells.
AB  - Little use has been made of flow cytometry in evaluating small intestinal
      epithelial cells. Obtaining pure epithelial cell populations devoid of peripheral
      blood contaminants and intraepithelial lymphocytes contributes to the
      difficulties encountered in flow cytometry studies. We have investigated the use
      of lectins as enterocyte specific cell markers using lectin histochemistry, and
      have identified one lectin, UEA-1, which binds exclusively and specifically to
      intestinal epithelial cell brush border. Additionally, we have exploited that
      specificity using flow cytometry and FITC-UEA-1 to identify and separate native
      intestinal epithelial cells from a mixed cell population isolated by mechanical
      vibration. This fluorescent-lectin technique is a unique and simple method to
      identify native small intestinal epithelial cells in a mixed cell population; it
      may be exploited by flow cytometric sorting of a pure population for biochemical
      study or as an enterocyte specific label for surface receptor flow cytometric
      studies in the research or clinical setting.

PMID- 14650445
TI  - Probenicid inhibition of fluorescence extrusion after MCB-staining of rat-1
      fibroblasts.
AB  - The intracellular fluorescence level of cells stained continuously with
      monochlorobimane was monitored by flow cytometry in order to assess the initial
      rate of glutatione to monochlorobimane conjugation as a measure of glutathione S
      transferase activity. In addition to a rapid initial increase and a plateau
      level, a decline in fluorescence intensity was found upon prolonged flow
      cytometric monitoring. Exposure to probenicid, an inhibitor of an ATP-dependent
      organic anion pump, prevented this decrease. Incubation with vanadate and
      verapamil was without effect. Thus, extrusion of fluorescentglutathione-conjugate
      perturbs the proportionality between initial glutathione level and
      monochlorobimane-dependent fluorescence intensity. Monitoring by flow cytometry
      the decrease in monochlorobimane-dependent fluorescence may be useful to detect
      multidrug resistant cells.

PMID- 14650446
TI  - Improved kinetic analysis of cytosolic free calcium in pressure-sensitive
      neuronal cells by fixed-time flow cytometry.
AB  - Two flow cytometric techniques were used to measure rapid transient changes in
      [Ca2+] in the neuronal cell line NH15-CA2. Using on-line injection, the cell
      suspension and stimulating solution are mixed and delivered to the detection
      point by a rapid increase in sample pressure. In NH15-CA2, injection of medium
      alone resulted in [Ca2+]i increase. Using the fixed-time method, where cells are
      maintained at constant pressure, no [Ca2+ ]i, increase was observed with medium
      alone. These results show that a rapid pressure increase alone alters the [Ca2+]i
      in NH15-CA2 cells. Both methods showed similar kinetics of [Ca2+], in response to
      bradykinin but the fixed-time method was found to be better for determination of
      the percentage of responsive cells.

PMID- 14650447
TI  - Clinical trial death from unregulated substance: Johns Hopkins recommends
      pharmacist and librarian collaboration.

PMID- 14650448
TI  - Can patients taking opioids drive safely? A structured evidence-based review.
AB  - A structured evidence-based literature review was completed to determine if there
      was epidemiological evidence of an association of opioid use and intoxicated
      driving, motor vehicle accidents (MVA) and MVA fatalities; to rate the quality of
      this research evidence according to Agency for Health Care Policy and Research
      (AHCPR) type of evidence and strength and consistency of the evidence rating
      scales; and according to this evidence determine whether patients taking opioids
      can drive safely. Relevant references were located from Medline, Psychological
      Abstracts, Science Citation Index and the National Library of Medicine Data Query
      databases by appropriate subject headings. A manual search was also performed
      utilizing the reference lists of the retrieved articles. All references relating
      to intoxicated driving, MVA and MVA fatalities were retrieved and reviewed in
      detail. Of these, references addressing opioid use were isolated and research
      information from these references was placed into tabular form under three major
      headings: Intoxicated driving and opioids; MVA and opioids; and MVA fatalities
      and opioids. Data were extracted from these references according to the following
      format: research question addressed, sample size, statistical analysis and
      results. The type of evidence each study represented was rated according to the
      AHCPR type of evidence rating scale. Each research area (intoxicated driving,
      MVA, MVA fatalities) represented by all the studies in each table was then rated
      utilizing the strength and consistency of the evidence AHCPR rating scale. Of the
      6 reports addressing intoxicated driving, 5 were well designed non-experimental
      studies and one was a well designed experimental study. All studies in this group
      reported a prevalence for opioid use which was approximately 1/10 that of the
      point prevalence use for opioids in the general population. This evidence
      indicated that opioids probably are not associated with intoxicated driving.
      Overall, the evidence indicates that opioids are not associated with MVA. Of the
      9 studies addressing MVA, 5 were well designed quasi-experimental studies and 4
      were well designed experimental studies. All reports in this group except one
      indicated that opioids are not associated with MVA. Of the 10 studies addressing
      MVA fatalities, 10 represented Type IV studies. For the vast majority of the
      studies, the prevalence percentages for an opioid association with MVA fatalities
      was 1/5 that of the point prevalence percentage for opioid use reported in the
      general population. Only 1 study reported a possible association between opioid
      use and MVA fatalities. The evidence in this review indicates that opioids do not
      appear to be associated with intoxicated driving, MVA and MVA fatalities, and
      consistently indicated that opioids are not associated with MVA. Although the
      comparison of point prevalence rates to the point prevalence may be problematic,
      the results of this systematic review support the contention that patients taking
      opioids may be allowed to drive. As in all clinical decisions, this determination
      should be individualized according to clinical factors.

PMID- 14650449
TI  - Clinical use of methadone.
AB  - Methadone hydrochloride is a mu-opioid agonist that has been used for the
      treatment of pain and for the management and maintenance of opioid withdrawal for
      over 50 years. Several characteristics make methadone a useful drug. However,
      these same characteristics and wide interpatient variability can make methadone
      difficult to use safely. A MEDLINE search was conducted on publications between
      January 1996 and May 2001 to identify literature relevant to this subject. Those
      publications were reviewed, and from them, other literature was identified and
      reviewed. Published studies demonstrate methadone's efficacy in pain management
      and in opioid withdrawal. However, interpatient variability in pharmacokinetic
      variables of methadone produces difficulties in developing guidelines for
      methadone use. Clinicians should not be deterred from use of this drug which has
      been shown to benefit patients in both pain management and methadone maintenance,
      but an individualized patient approach must be taken to use methadone safely.

PMID- 14650450
TI  - Palliative care: an international necessity.
AB  - Palliative care is the care of patients whose disease is incurable and whose life
      expectancy is limited to weeks or months. This commentary describes the
      development of modern palliative care, some of the elements and underlying
      philosophical constructs of such care, and calls for expansion and improvement in
      end of life care throughout the world.

PMID- 14650451
TI  - Moral lessons from the jury box.
AB  - A decade ago a North Carolina jury awarded millions of dollars in damages because
      of a healthcare institution's failure to provide appropriate pain relief to a
      dying patient. In 2001, a California jury found a physician guilty of elder abuse
      for his failure to properly manage the pain of a cancer patient. In both
      instances, state licensing boards had failed to take any disciplinary action
      against those involved. These cases dramatically illustrate a significant and
      persistent gulf between the lay public and the health professions with regard to
      the moral significance they attach to the duty to relieve suffering. Measures to
      insure that all patients receive effective assessment and management of their
      pain must take into account this disparity, and endeavor to achieve congruence by
      reconnecting the health professions to their ancient and core value--the relief
      of suffering.

PMID- 14650453
TI  - Myofascial pain response to topical lidocaine patch therapy: case report.
AB  - This is a case from a preliminary open trial to assess the efficacy of topically
      applied lidocaine patches as an alternative to trigger point injections for
      myofascial pain. We describe one case in this report that had a dramatic response
      to the lidocaine patch. Her pain relief increased, pain intensity decreased, and
      functional capacity increased. Her pain intensity and relief was measured by the
      Brief Pain Inventory-Short Form (BPI-SF). A quality of life measure was also
      included in the BPI-SF. While this was a dramatic response to this patient, it is
      only one case from an open-trial. The response to other patients has varied. The
      true clinical utility cannot be obtained from this one report, but only after the
      data have been analyzed from this initial trial. If the data are promising, a
      randomized, double-blind, crossover trial is planned.

PMID- 14650452
TI  - Analgesia issues in palliative care: bone pain, controlled release opioids,
      managing opioid-induced constipation and nifedipine as an analgesic.
AB  - Some recent literature relevant to analgesia in palliative care is reviewed.
      Reports on clinical use of bisphosphonates for bone pain in cancer, controlled
      release opioids, selection of laxatives for opioid-induced constipation and the
      calcium channel blocker nifedipine as an analgesic are described.

PMID- 14650454
TI  - Opiophobia as a barrier to the treatment of pain.
AB  - An international panel of pain specialists including physicians and health policy
      scholars met to discuss the impact of fear of opioids on the clinical use of
      these strong analgesics. Recognizing potential risk from opioids, the panel
      members concluded that irrational fear of the drugs often impedes their
      appropriate use. The need for education among clinicians was recognized and the
      panel concluded that while progress has been made, much remains to be done to
      correct unfounded fears and misconceptions that impede provision of opioid
      analgesia when it is indicated.

PMID- 14650455
TI  - Urine drug screening for opioids.

PMID- 14650456
TI  - Evidence-based pain management and palliative care.

PMID- 14650457
TI  - Patient-specific factors affecting patient-controlled analgesia dosing.
AB  - A study was conducted to evaluate the effect of characteristics patients' gender,
      age, weight, height, and body surface area, as well as the concurrent or recent
      use of opioids, ethanol and tobacco, on opioid dose requirements during
      administration of patient-controlled analgesia (PCA). Data were collected
      retrospectively from the medical records of 150 patients who underwent open
      cholecystectomies during an 18 month period at one institution. Demonstrable
      inter-patient variability in patterns of PCA use was observed. The results of the
      study demonstrate that during the first 48 hours of PCA therapy, patient age,
      height, weight, body surface area, gender, smoking, alcohol use, and preoperative
      opioid use may have significant influence on opioid analgesic use (p < 0.05). The
      data support the hypothesis that patient-specific factors may contribute to the
      variability observed in patients' PCA analgesic dose requirements, and these
      factors should be considered when selecting a proper demand (bolus) dose for PCA
      therapy.

PMID- 14650459
TI  - An annotated guide to pain and palliative care on the World Wide Web.
AB  - Two dozen leading sites on the World Wide Web that pertain to pain management and
      palliative care are listed and described. Strengths and limitations are
      discussed.

PMID- 14650458
TI  - What is the most effective therapy for preventing NSAID-induced gastropathy?
AB  - Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal toxicity is
      associated with morbidity and mortality, and given the very wide use of NSAIDs,
      is problematic and costly to society. Several options are now available to
      minimize gastrointestinal toxicity from NSAIDs. These options include the proton
      pump inhibitors, misoprostil, double-dose H2-receptor blockers and the COX-2
      selective NSAIDs. No head-to-head clinical trials have compared these options.
      The effectiveness of these strategies to minimize NSAID-induced gastrointestinal
      toxicity is summarized. In addition, their associated adverse effect profiles and
      costs are compared.

PMID- 14650460
TI  - Medications through the Internet: what clinicians and patients need to know.
AB  - Patients are now able to obtain mail order prescriptions through the Internet
      from reputable online pharmacies without leaving their home. While this can be a
      great convenience, the Internet also provides a new means for easily questionable
      or even illegal prescription medications, i.e., prescription legend medications
      may be obtained without a prescription and drug products not legally available in
      the United States can be obtained in this way. Many chronic pain patients are
      drug seeking, and increasingly many are using the Internet to learn about
      medications, and perhaps to obtain them. Clinicians should know where their
      patients obtain medications, how to verify the validity of the sources of
      prescriptions, and how to report fraud. Ways to verify the legitimacy of an
      online pharmacy are described.

PMID- 14650461
TI  - Report from the ASHP 36th Midyear Clinical Meeting.
AB  - The ASHP Midyear Clinical meeting continues to be the largest pharmacy meeting in
      the world. A broad range of topics was presented at hundreds of symposia and
      posters at the 2001 meeting in New Orleans, Louisiana, in December. Pain
      management, hospice care, evidence based medicine, safe medication practices and
      improved drug information services were among the many practice areas addressed
      and recognized at the meeting.

PMID- 14650462
TI  - The Cochrane Collaboration Pain, Palliative Care and Supportive Care
      Collaborative Review Group.
AB  - The Pain, Palliative and Supportive care group is one of 50 collaborative review
      groups that make up the Cochrane Collaboration, an international organization
      with the task of preparing, maintaining and disseminating systematic reviews of
      the effects of healthcare. Cochrane reviews are published cumulatively four times
      a year on the Cochrane library (CD-ROM and Web-based), along with other useful
      material such as a register of some 300,000 randomized controlled trials. The
      group has identified some 20,000 randomized trials in pain and 1,200 in
      palliative care. Reviews in progress are also published on the library as
      protocols. Full peer-review is undertaken for protocols and reviews. The Pain,
      Palliative and Supportive care group is an informal international team involving
      some 100 people from some 18 countries. The group has published 26 protocols and
      17 full reviews with a further 50 reviews in progress. The task is huge and there
      is scope for further volunteers to help with the various tasks of writing
      reviews, peer reviewing and literature searching.

PMID- 14650463
TI  - Pain and palliative care in Issue Number 3, 2001 of The Cochrane Library.
AB  - A brief description of how an individual can access The Cochrane Library and
      navigate within it is provided. The National Library of Medicine medical subject
      heading (MeSH) terminology is described. Selected new reviews from a recent
      edition of The Cochrane Library are listed in an annotated bibliography together
      with a description of the current volume of material now available on the
      library.

PMID- 14650464
TI  - Analgesic issues in palliative care gastroesophageal reflux pain and chronic non
      cancer pain management.
AB  - Brief literature reviews and commentary on gastroesophageal reflux disease
      associated pain management with rectal dosage forms and beliefs about use of
      opioids in non-cancer pain are presented. Relevant references including the model
      guidelines of the Federation of State Medical Boards of the United States on the
      use of opioids in non-cancer pain are cited.

PMID- 14650465
TI  - Management of cancer pain evidence report technology assessment: number 35-
      management of cancer pain summary.
AB  - Under its Evidence-Based Practice Program, the Agency for Healthcare Research and
      Quality (AHRQ) is developing scientific information for other agencies and
      organizations on which to base clinical guidelines, performance measures, and
      other quality improvement tools. Contractor institutions review all relevant
      scientific literature on assigned clinical care topics and produce evidence
      reports and technology assessments, conduct research on methodologies and the
      effectiveness of their implementation, and participate in technical assistance
      activities.

PMID- 14650466
TI  - Urine opioid screens may be misleading.

PMID- 14650467
TI  - Investigation and management of ischemic colitis.
AB  - The colon is the most common site of gastrointestinal ischemia. The condition
      resolves completely with conservative treatment in most cases, but late diagnosis
      or severe ischemia can be associated with high rates of complications and death.
      Once ischemic colitis is diagnosed, serial physical examinations and
      colonoscopies are helpful to follow the condition. Prompt surgery is required for
      severe episodes, when conservative measures fail, and for patients with chronic
      symptoms.

PMID- 14650468
TI  - The Russian health care system today: can American-Russian CME programs help?
AB  - The health of the Russian people has deteriorated dramatically since the fall of
      communism, due particularly to cardiovascular disease. The Eurasian Medical
      Education Program was developed in response to provide continuing medical
      education for Russian physicians. Programs are directed mainly toward primary
      care physicians and focus on outpatient management of diseases that cause high
      rates of mortality and morbidity. This experience provides an opportunity to
      assess the structure and functioning of the Russian health care system and
      emphasizes the importance of general internal medicine training in detection,
      management, and prevention of disease complications.

PMID- 14650469
TI  - Alcohol and health: a drink a day won't keep the doctor away.
AB  - We should not advise patients to start drinking alcohol for its alleged
      cardiovascular benefits. The negative effects of alcohol are well established,
      and the evidence of alcohol's benefits comes mainly from epidemiologic studies
      that were not well controlled for other influences, such as lifestyle factors.
      Moreover, we have other means of lowering cardiovascular risk that are safe and
      proven. Those who are healthy and whose drinking history shows little risk of
      developing alcohol dependency may continue to drink moderate amounts. Heavy
      drinkers should be advised to quit.

PMID- 14650470
TI  - Scleroderma: a treatable disease.
AB  - Many effective treatments for scleroderma have emerged in recent years, including
      bosentan, an endothelin receptor antagonist, and epoprostenol, a prostacyclin,
      both of which target vasoconstriction. Cyclophosphamide may soon be proven
      effective against interstitial lung disease.

PMID- 14650471
TI  - When patients on warfarin need surgery.
AB  - When a patient who has been taking warfarin long-term needs to undergo surgery,
      how to manage his or her anticoagulation is controversial. We believe most
      patients should stop taking warfarin 5 days before elective surgery, and most do
      not need to receive heparin in the perioperative period as a bridge to surgery.

PMID- 14650472
TI  - Talking to patients about St. John's wort.
AB  - St. John's wort, an unregulated herbal supplement widely used as a self-treatment
      for depression, can cause side effects and drug interactions. Physicians should
      ask their patients about use of over-the-counter products such as St. John's wort
      and discuss their use in a frank but nonjudgmental manner.

PMID- 14650473
TI  - Patient information. Straight talk about St. John's wort.

PMID- 14650474
TI  - The Heart Protection Study: high-risk patients benefit from statins, regardless
      of LDL-C level.
AB  - The landmark Heart Protection Study (Lancet 2002; 360:7-22) found benefit in
      treating subjects at high risk of a coronary event with simvastatin 40 mg daily,
      regardless of baseline low-density lipoprotein cholesterol level and in all
      subgroups, including women and the elderly. The study found no benefit of
      simvastatin therapy in preventing noncardiac events (eg, dementia, osteoporotic
      fractures), and no negative effects, such as an increase in cancer, respiratory
      disease, or suicide.

PMID- 14650475
TI  - Atrial fibrillation.

PMID- 14650476
TI  - Human rights: dispensable when convenient?

PMID- 14650477
TI  - In the company of women: enacting autonomy within the perinatal nursing
      relationship.
AB  - An understanding of autonomy has important significance in North American health
      care. Although a respect for autonomy is necessary to protect the self
      determination and agency of birthing women in hospital settings, I suggest that
      enactments of autonomy that are independent of relationships offer only an
      incomplete interpretation of such a vital concept. In this article I explore an
      understanding of autonomy situated within the context of a relational birthing
      narrative. In so doing, autonomy becomes conceptualized as contextual and
      concrete, giving rise to an embodied view of the birthing woman.

PMID- 14650478
TI  - The practice setting: site of ethical conflict for some mothers and midwives.
AB  - Practitioners' ethical orientation and responses vary between practice settings.
      Yet, currently, the ethics for midwifery practice that is explicit in the
      literature and which provides the ideals of socialization into practice, is that
      of bio(medical)ethics. Traditional bioethics, developed because of World War II
      atrocities and increased scientific research, is based on moral philosophy,
      normative theory, abstract universal principles and objective problem solving,
      all of which focus on right and wrong 'action' for resolving dilemmas. They
      exclude context and relationship. Personal narratives of mothers and midwives
      contest the appropriateness of these accepted values and systems for childbirth
      because they induce conflict between workplace/service provider ethics and
      personal/professional midwifery ethics. In contrast to the disembedded and
      disembodied approach of biomedical ethics, an ethically adequate response in
      midwifery practice resonates more with the ethics of intimates, such as feminist
      virtue ethics.

PMID- 14650479
TI  - Preserving integrity: experiences of people with mental health problems living in
      their own home in a new neighbourhood.
AB  - For patients with mental health problems, de-institutionalization has meant a
      shift from institutional care to living in the community. However, several
      studies show that problems of stigmatization, loneliness and negative attitudes
      devalue the dignity and autonomy of these patients. The aim of this study was to
      gain a deeper understanding of how people with mental health problems experience
      living in an apartment of their own. The data collection method was focus group
      interviews. The constant comparative method revealed the main category
      'preserving integrity'. The subcategories were: the need for control over
      information, similar relationships with both friends and neighbours (symmetrical
      contact), and 'My home is my castle'. Participants who lived in a group home had
      little or no contact with their neighbours. The participants experienced lack of
      acceptance and loss of autonomy when meeting people. Integrity was a necessary
      condition in order for them to become equal citizens, experience autonomy and
      dignity, and have the opportunity to develop social contacts.

PMID- 14650480
TI  - Struggling to become ready for consolation: experiences of suicidal patients.
AB  - Although there has been a vast amount of research about suicide, very few studies
      focus on the inner world of the suicidal patient. A secondary analysis of two
      exemplar narrative interviews with Norwegian patients reveals a glimpse of the
      inner world of suicidal patients' longing for consolation. The results of a
      phenomenological hermeneutic study inspired by Ricoeur's philosophy reveal five
      themes and one main theme. The themes are: 'longing for closeness', 'desiring
      connectedness', 'struggling to open up inner dialogue', 'breaking into outer
      dialogue', and 'liberating inner and outer dialogue'. The main theme is
      'struggling to become ready for consolation'. These results describe a process of
      becoming ready for consolation, which, when interpreted in the light of the model
      of consolation by Norberg et al., reveals that the end of the process of becomin
      ready for consolation is consolation itself as praxis.

PMID- 14650481
TI  - Korean nurses' attitudes to good and bad death, life-sustaining treatment and
      advance directives.
AB  - This study was an investigation of which distinctive elements would best describe
      good and bad death, preferences for life-sustaining treatment, and advance
      directives. The following elements of a good death were identified by surveying
      185 acute-care hospital nurses: comfort, not being a burden to the family, a good
      relationship with family members, a readiness to die, and a belief in perpetuity.
      Comfort was regarded as the most important. Distinctive elements of a bad death
      were: persistent vegetative state, sudden death, pain and agony, dying alone, and
      being a burden to the family. Of the 185 respondents, 90.8% answered that they
      did not intend to receive life-sustaining treatment if they suffered from a
      terminal illness without any chance of recovery; 77.8% revealed positive
      attitudes toward advance directives. Sixty-seven per cent of the respondents
      stated that they were willing to discuss their own death and dying; the
      perception of such discussions differed according to the medical condition (p =
      0.001). The elements of a bad death differed significantly depending on the
      disease state (p = 0.003) and on economic status (p = 0.023).

PMID- 14650482
TI  - Korean nursing students' ethical problems and ethical decision making.
AB  - This Korean study replicated a previously published American study. The
      conceptual framework and method combined ethical enquiry and phenomenology. The
      research questions were: (1) What is nursing students' experience of ethical
      problems involving nursing practice? and, (2) What is nursing students'
      experience of using an ethical decision-making model? The participants were 97
      senior baccalaureate nursing students, each of whom described one ethical problem
      and chose to use one of five ethical decision-making models. From 97 ethical
      problems, five content categories emerged, the largest being health professionals
      (69%). The basic nature of the ethical problems was the students' experience of
      conflict, resolution and rationale. Using an ethical decision-making model helped
      94% of the students. A comparison of the Korean and American results yields
      important implications for nursing ethics education, practice and research.

PMID- 14650483
TI  - Professional values and norms for nurses in Belgium.
AB  - Because of their responsibilities for providing high-quality care, at times when
      they are continuously confronted with inherent professional and ethical
      challenges, nurses should meet high ethical standards of practice and conduct.
      Contrary to other countries, where codes of ethics for nurses are formulated to
      support those standards and to guide nurses' professional practice, Belgian
      nurses do not have a formal code of ethics. Nevertheless, professional ethics is
      recognized as an important aspect in legal and other professional documents. The
      aim of this article is to illustrate that codes of ethics are not the only
      professional documents reflecting nurses' values, norms and responsibilities.
      Other documents can also set out professional nursing ethics, and as such replace
      codes of ethics.

PMID- 14650484
TI  - The ethics of nurse poaching from the developing world.
AB  - Recruiting nurses from other countries is a long-standing practice. In recent
      years many countries in the developed world have more frequently recruited nurses
      from the developing world, causing an imbalance in the health services in often
      already impoverished countries. Despite guidelines and promises by developed
      countries that the practice should cease, it has largely failed to do so. A
      consortium of authors from countries that have experienced significant nurse
      poaching consider the ethical aspects behind this continuing practice.

PMID- 14650485
TI  - Reconfigurable electro-optical waveguide for optical processing.
AB  - A highly versatile electro-optically induced waveguide is proposed, and some of
      its applications are discussed. The In(1-s)Ga(s)As(t)P(1-t)-based device can
      reconfigure an arbitrary refractive-index profile with high speed by using an
      array of stripe electrodes deposited along the device. This device can act as a
      variable fractional Fourier transformer or as a beam shaper. Some nonguiding
      applications based on a specific refractive-index patterning that is normal to
      the light-propagation direction, such as phase modulation and beam steering, can
      also be implemented with this device.

PMID- 14650486
TI  - Partitioned-field holographic lenses composed of three noncentered uniaxial
      systems.
AB  - Partitioned-field uniaxial volume holographic lenses increase the image fields of
      holographic volume lenses that are limited by angular selectivity. The efficiency
      and aberrations of one of these systems consisting of two overlapping uniaxial
      noncentered lenses were reported previously [Appl. Opt. 38, 4011 (1999)]. In the
      present study we present theoretical and experimental extensions of these systems
      to three overlapping lenses, showing how the dynamic range of the recording
      material can cause an important decrease in efficiency when several gratings are
      superposed on the same plate.

PMID- 14650487
TI  - Image reconstruction for in-line holography with the Yang-Gu algorithm.
AB  - A new approach to the numerical reconstruction of wave fronts stored by in-line
      holography is presented. The new algorithm can achieve good reconstructed results
      in both unitary and nonunitary systems. The influences of recording distance and
      noise as well as of digitalization errors on the quality of reconstruction are
      numerically investigated. The experimental results demonstrate the validity of
      this new approach.

PMID- 14650488
TI  - Digital shearing method for three-dimensional data extraction in holographic
      particle image velocimetry.
AB  - We report a new digital shearing method for extracting the three-dimensional
      displacement vector data from double-exposure holograms. With this method we can
      manipulate both the phase and the amplitude of the recorded signal, which, like
      optical correlation analysis, is inherently immune to imaging aberration.
      However, digital shearing is not a direct digital implementation of optical
      correlation, and a considerable saving in computation time results. We
      demonstrate the power of the method by MATLAB simulation and discuss its
      performance with reference to optical analysis.

PMID- 14650489
TI  - Comparison of measurements made with two different instruments of the same
      atmospheric vertical profile.
AB  - The validation of atmospheric remote-sensing measurements involves the comparison
      of vertical profiles of atmospheric constituents obtained by different
      instruments. This operation is a complex one because it has to take into account
      the measurement errors that are described by the variance-covariance matrices and
      the different features of the two observing systems that are described by the
      averaging kernels. The procedure is discussed and a method of comparison that is
      rigorous and does not involve degradation of the available information is
      developed by use of the formalism of functional spaces. The functional spaces
      that can be used for representation of the two profiles are reviewed, and
      criteria are determined for the choice of the most convenient functional space to
      minimize degradation of the measurements. Once the functional spaces are chosen,
      the components of the profiles are compared in the intersection space of these
      two functional spaces. If the intersection space coincides with the null vector,
      a pseudointersection space with useful geometrical properties can be used
      instead. A test of the method is made with a realistic simulation. In the test
      the profiles retrieved by two real instruments are simulated and quantitatively
      compared.

PMID- 14650490
TI  - Object recognition in subband transform-compressed images by use of correlation
      filters.
AB  - We introduce subband correlation filters (SCFs) as a solution to the problem of
      object recognition at multiple resolution levels in quantized transformed
      imagery. The approach synthesizes correlation filters that operate directly on
      subband coefficients rather than on image data. We explore two techniques to
      accomplish the reduced-resolution recognition: (1) training the correlation
      filters to incorporate downsampling tolerance and (2) adaptation of the subband
      decomposition filters to accommodate the reduced resolutions. For compression
      ratios of 20:1, SCFs demonstrate recognition performance of at least 90%, 85%,
      and 75%, respectively, on 2-, 4-, and 8-ft-resolution synthetic aperture radar
      data.

PMID- 14650491
TI  - A method for local deconvolution.
AB  - A new method for deconvolution of one-dimensional and multidimensional data is
      suggested. The proposed algorithm is local in the sense that the deconvolved data
      at a given point depend only on the value of the experimental data and their
      derivatives at the same point. In a regularized version of the algorithm the
      deconvolution is constructed iteratively with the help of an approximate
      deconvolution operator that requires only the low-order derivatives of the data
      and low-order integral moments of the point-spread function. This algorithm is
      expected to be particularly useful in applications in which only partial
      knowledge of the point-spread function is available. We tested and compared the
      proposed method with some of the popular deconvolution algorithms using simulated
      data with various levels of noise.

PMID- 14650492
TI  - Optical scanning cryptography for secure wireless transmission.
AB  - We propose a method for secure wireless transmission of encrypted information. By
      use of an encryption key, an image or document is optically encrypted by optical
      heterodyne scanning and hence encryption is performed on the fly. We call this
      technique optical scanning cryptography. The output of the heterodyne encrypted
      signal is at radio frequency and can be directly sent through an antenna to a
      secure site for digital storage to be prepared for decryption. In the secure
      site, an identical optical scanning system to that used for encryption is used,
      together with a decryption key, to generate an electrical signal. The electrical
      signal is then processed and sent to a computer to be used for decryption.
      Utilizing the stored information received from the encryption stage and the
      electrical information from the secure site, a digital decryption unit performs a
      decryption algorithm. If the encryption key and the decryption key are matched,
      the decryption unit will decrypt the image or document faithfully. The overall
      cryptosystem can perform the incoherent optical processing counterpart of the
      well-known coherent double-random phase-encoding technique. We present computer
      simulations of the idea.

PMID- 14650493
TI  - Instantaneous frequency and its application to strain extraction in moire
      interferometry.
AB  - Moire interferometry is an effective experimental technique for measurement of in
      plane deformation. However, it is information on the derivatives of the
      deformation, i.e., strains, that is usually desired in experimental mechanics. It
      is shown that the desired strains are the instantaneous frequencies of the fringe
      pattern and that either an energy operator or wavelet ridges can be used to
      extract the instantaneous frequencies from a single fringe pattern. The energy
      operator is a pixelwise processor; thus the strain extraction can be done on the
      fly, but it is sensitive to noise. The wavelet ridges extract the local features
      in the fringe pattern. The strain extraction is thus insensitive to noise, and
      good results are obtainable at the cost of longer computation time. The two
      methods can thus be chosen for different needs in strain analysis. The properties
      of the two methods as well as their applications to a real fringe pattern are
      given. The effectiveness of the proposed methods is illustrated by their
      comparison with traditional methods.

PMID- 14650494
TI  - Determination of global phase shifts between interferograms by use of an energy
      minimum algorithm.
AB  - A new algorithm for precise determination of the global phase shift between two
      interferograms is introduced. First we calculate the frame difference between the
      first and the second interferogram; the difference is multiplied by a properly
      chosen test phase factor, and then we implement a two-dimensional Fourier
      transform of the frame difference and calculate the energy of the first positive
      (or negative) diffraction order. An iterative approach is used for the test phase
      to ensure that the minimum energy is obtained, and then the correct phase shift
      value is found. This method is called the energy-minimum Fourier transform
      method, which is accurate and noise insensitive compared with the single-point
      Fourier transform method. Both the theoretical analysis and experimental results
      are given.

PMID- 14650495
TI  - Four-dimensional microscopy of defects in integrated circuits.
AB  - We demonstrate four-dimensional microscopy of defects in integrated circuits by a
      technique that combines laser-scanning confocal reflectance microscopy with one
      photon optical-beam-induced current (1P-OBIC) imaging. Accurate information is
      obtained about the three-dimensional structure of the defect and the kind of
      material (metal, semiconductor, or dielectric) that is damaged by the defect. The
      same focused probe beam simultaneously produces the 1P-OBIC and reflectance
      signals from the illuminated sample spot. The hardware development cost is
      minimal for a laser-scanning confocal microscope, and the image reconstruction
      procedure is computationally efficient. Imaging is demonstrated on defects that
      are caused by electrical overstress and unwanted generation centers. Exclusive
      three-dimensional distributions of the semiconductor and metal sites in the
      integrated circuit reveal defect features that are difficult to recognize with
      confocal or 1P-OBIC imaging alone.

PMID- 14650496
TI  - Nonlinear signal-processing model for scalar diffraction in optical recording.
AB  - A nonlinear signal-processing model is derived for the optical recording channel
      based on scalar diffraction theory. In this model, the signal waveform is written
      in closed form as an explicit function of the channel bits that are stored on an
      optical disk, thereby comprising both linear and nonlinear terms. Its explicit
      dependence on the channel bits makes this model well suited for signal-processing
      purposes. With the model it is also convenient to assess the importance of
      nonlinear contributions to the signal waveform. The model is applied for one
      dimensional optical storage as well as for two-dimensional (2D) optical storage
      in which bits are arranged on a 2D hexagonal lattice. Signal folding is addressed
      as a typical nonlinear issue in 2D optical storage and can be eliminated by
      recording of pit marks of sizes considerably smaller than the size of the
      hexagonal bit cell. Further simplifications of the model with only a limited
      number of channel parameters are also derived.

PMID- 14650497
TI  - Optical characteristics of the compound PLZT.
AB  - We present a summary of measured characteristics of lanthanum-doped lead
      zirconium titanate (PLZT) compound in its mechanical housing. It is expected that
      the PLZT device will be used as the main component in an ultrafast electro-optic
      switch. We have performed several experiments to measure and calculate the
      following characteristics: optical power transmission, thermodynamic effects,
      switching speed, and dc drift phenomenon.

PMID- 14650498
TI  - Fractional Fourier transform optical system with programmable diffractive lenses.
AB  - We present experimental results for a fractional Fourier transform (FRFT) system
      implemented with programmable lenses written onto a liquid-crystal spatial light
      modulator (LCSLM). Because the focal length can be changed, different orders of
      the FRFT can be obtained without changing the optical setup. The LCSLM can very
      easily implement more complicated operations, including the realization of
      simultaneous orders of the FRFT and anamorphic transforms.

PMID- 14650499
TI  - Predictive validity of critical thinking skills for initial clinical dental
      hygiene performance.
AB  - This study collected validity evidence on the utility of critical thinking skills
      and critical thinking disposition in predicting initial clinical performance. The
      predictive value of critical thinking skills scores and disposition scores was
      examined to determine their unique contribution beyond that provided by
      traditional predictors: grade point average, age, and number of college hours.
      The study involved three phases: establishing content validity of three outcome
      measures; assessing students' baseline critical thinking skills and disposition
      using the California Critical Thinking Skills Test (CCTST) and the California
      Critical Thinking Dispositions Inventory (CCTDI); and assessing students' initial
      clinical competence, clinical reasoning, and clinical knowledge. All
      baccalaureate-level dental hygiene programs in the United States affiliated with
      a dental school (N=22) were invited to participate; of those, seven volunteered.
      A convenience sample of 207 first-year dental hygiene students was obtained. A
      series of hierarchical multiple regression analyses demonstrated that CCTST
      scores explained a statistically significant (p<.05) proportion of variance in
      students' initial clinical reasoning scores, acquired knowledge scores, and
      faculty ratings, above and beyond that explained by other predictor variables.
      CCTDI scores were not significant predictors of any outcome measure. It was
      concluded that CCTST is a good predictor of initial student outcomes and may have
      utility for student selection and retention.

PMID- 14650500
TI  - Dental informatics: an emerging biomedical informatics discipline.
AB  - Biomedical informatics is a maturing discipline. During the last forty years, it
      has developed into a research discipline of significant scale and scope. One of
      its subdisciplines, dental informatics, is beginning to emerge as its own entity.
      While there is a growing cadre of trained dental informaticians, dental faculty
      and administrators in general are not very familiar with dental informatics as an
      area of scientific inquiry. Many confuse informatics with information technology
      (IT), are unaware of its scientific methods and principles, and cannot relate
      dental informatics to biomedical informatics as a whole. This article delineates
      informatics from information technology and explains the types of scientific
      questions that dental and other informaticians typically explore. Scientific
      investigation in informatics centers primarily on model formulation, system
      development, system implementation, and the study of effects. Informatics draws
      its scientific methods mainly from information science, computer science,
      cognitive science, and telecommunications. Dental informatics shares many types
      of research questions and methods with its parent discipline, biomedical
      informatics. However, there are indications that certain research questions in
      dental informatics require novel solutions that have not yet been developed in
      other informatics fields.

PMID- 14650501
TI  - The utility of Canadian DAT Perceptual Ability and Carving Dexterity scores as
      predictors of psychomotor performance in first-year operative dentistry.
AB  - This study sought to determine if Canadian Dental Aptitude Test Perceptual
      Ability (PA) and Carving Dexterity (CD) scores have any practical utility as
      predictors of psychomotor performance. Simple linear regression and multiple
      regression analyses were performed and prediction intervals plotted. Efforts were
      made to expand the range of the predictor and dependent variables and to improve
      the accuracy and consistency and prevent contamination of the dependent
      variables. Results for both PA and CD varied markedly across years. Weak, but
      statistically extremely significant, correlations were observed for both PA and
      CD with specific technique grades and the year-overall pooled data. PA
      correlations loaded on exams at the start, and CD correlations loaded on exams at
      the end of the year. Manual average scores exhibited the strongest correlation
      with year-overall technique grades, but could explain no more than 7.2 percent of
      observed variance. Prediction intervals for year-end grades spanned at least 38
      percentage grade points for both PA and CD. Within the context of the present
      study, PA and CD scores demonstrated no practical utility as predictors of
      psychomotor performance.

PMID- 14650502
TI  - Developing high-quality educational software.
AB  - The development of effective educational software requires a systematic process
      executed by a skilled development team. This article describes the core skills
      required of the development team members for the six phases of successful
      educational software development. During analysis, the foundation of product
      development is laid including defining the audience and program goals,
      determining hardware and software constraints, identifying content resources, and
      developing management tools. The design phase creates the specifications that
      describe the user interface, the sequence of events, and the details of the
      content to be displayed. During development, the pieces of the educational
      program are assembled. Graphics and other media are created, video and audio
      scripts written and recorded, the program code created, and support documentation
      produced. Extensive testing by the development team (alpha testing) and with
      students (beta testing) is conducted. Carefully planned implementation is most
      likely to result in a flawless delivery of the educational software and
      maintenance ensures up-to-date content and software. Due to the importance of the
      sixth phase, evaluation, we have written a companion article on it that follows
      this one. The development of a CD-ROM product is described including the
      development team, a detailed description of the development phases, and the
      lessons learned from the project.

PMID- 14650503
TI  - Evaluation of educational software.
AB  - Evaluation is an important component of developing educational software. Ideally,
      such evaluation quantifies and qualifies the effects of a new educational
      intervention on the learning process and outcomes. Conducting meaningful and
      rigorous educational evaluation is difficult, however. Challenges include
      defining and measuring educational outcomes, accounting for media effects, coping
      with practical problems in designing studies, and asking the right research
      questions. Practical considerations that make the design of evaluation studies
      difficult include confounding, potentially small effect sizes, contamination
      effects, and ethics. Two distinct approaches to evaluation are objectivist and
      subjectivist. These two complement each other in describing the whole range of
      effects a new educational program can have. Objectivist demonstration studies
      should be preceded by measurement studies that assess the reliability and
      validity of the evaluation instrument(s) used. Many evaluation studies compare
      the performance of learners who are exposed to either the new program or a more
      traditional approach. However, this method is problematic because test or exam
      performance is often a weak indicator of competence and may fail to capture
      important nuances in outcomes. Subjectivist studies are more qualitative in
      nature and may provide insights complementary to those gained with objectivist
      studies. Several published examples are used in this article to illustrate
      different evaluation methods. Readers are encouraged to contemplate a wide range
      of evaluation study designs and explore increasingly complex questions when
      evaluating educational software.

PMID- 14650504
TI  - The predictive utility of computer-simulated exercises for preclinical technique
      performance.
AB  - The objective of this research was to determine if a computerized simulated
      dental exercise predicts students' subsequent performance in preclinical
      technique courses. Twenty-nine first-year dental students voluntarily
      participated in the investigation prior to their first experience with a dental
      handpiece. These students prepared an ideal Class I amalgam on an ivorine
      mandibular first molar tooth after viewing ten-minute videotaped instructions.
      Students completed the Class I amalgam on a computerized dental treatment
      simulator (SIM). All participants' SIM scores were correlated with sub-test
      scores of the Dental Admission Test (DAT), predental overall grade point average
      (GPA), predental Biology/Chemistry/Physics grade point average (BCP), and grades
      from the first two preclinical laboratory technique courses (Lab 1 and Lab 2).
      The results showed a significant correlation between the simulator scores and DAT
      sub-test scores of Academic Average and Total Science, as well as Lab 1 scores.
      Based on these results, the simulator appears to be a good measure of general
      cognitive ability, including cognitive ability required to complete uncomplicated
      preclinical exercises.

PMID- 14650505
TI  - Reflective learning in community-based dental education.
AB  - Learners gain additional value from community-based education when they are
      guided through a reflective process. The purpose of this article is to describe
      how structured reflection assignments and methods are incorporated in the
      University of North Carolina School of Dentistry's community-based DISC
      (Dentistry in Service to Communities) program. The following strategies are
      described as ways to enrich community-based learning experiences for dental
      students: photographic documentation; written narratives; critical incident
      reports; and mentored post-experiential small group discussions. Fieldwork and
      course-related examples are drawn from community-based dental experiences to
      illustrate how reflective teaching approaches can enhance student learning. A
      directed process of reflection is suggested as a way to increase the impact of
      the community learning experience.

PMID- 14650506
TI  - Identifying and responding to competing needs: a case study of a dental school
      operated community dental clinic.
AB  - Dental schools face challenges and competing needs when they seek to initiate or
      expand their community dental programs. This article uses a dental school
      community clinic as a case study to frame the tensions between competing needs of
      educational requirements, access to dental care, financial viability, and service
      to the community that clinics must learn to manage if they are to be successful.
      The identification of competing needs provides community-oriented dental school
      clinics the ability to examine factors that come into play as communities and
      their environments change. The outcome of this assessment process is strategies
      that can facilitate the provision of a higher level of services more efficiently,
      while at the same time taking into account future limitations in availability of
      resources. The concluding section of this article presents a model for a
      community-based dental clinic that is directed more toward patient care, involves
      dentists/specialists as primary providers, allows postdoctoral residents to take
      on more responsibility, and allows dental students to provide patient care on a
      more regular and longitudinal basis.

PMID- 14650507
TI  - Personality and gender influences on faculty ratings and rankings of oral and
      maxillofacial surgery residency applicants.
AB  - This study examined effects of applicants' personality and gender on faculty
      rankings and matching to an Oral and Maxillofacial Surgery (OMS) residency
      program. Forty-seven applicants completed a standardized personality measure
      (Adjective Check List, ACL), and faculty interviewers rated each applicant on
      five personality dimensions during their onsite interview. Applicants were found
      to be similar to the normative population on all ACL personality dimensions,
      indicating that there is no distinctive personality profile characteristic of
      individuals seeking an OMS residency position. Male applicants were rated by
      interviewers as being more capable of dealing with stress effectively and more
      affiliative and deferent to authority than female applicants. Applicant ACL
      scores were unrelated to faculty rankings, but applicants rated as more friendly,
      motivated, assertive, confident, and tolerant of stress received more favorable
      rankings. Compared to applicants who did not match at this site, matched
      applicants were more likely to seek emotional support from others and were rated
      as being more assertive. Study limitations as well as implications for the use of
      personality measures and interviews in the selection of OMS residency candidates
      are discussed.

PMID- 14650508
TI  - Dispersion of Homalodisca coagulata (Hemiptera: Cicadellidae), a vector of
      Xylella fastidiosa, into vineyards in southern California.
AB  - Recent epidemics of Pierce's disease of grapevine in California vectored by
      Homalodisca coagulata (Say), an invasive vector species, have characteristics
      that differ from epidemics involving native vectors. Among these differences are
      the longer distances and greater speed that the disease is spread by H.
      coagulata. In this investigation, we used yellow sticky traps to study the
      seasonal dispersion activity of H. coagulata in a southern California grape
      growing area in which an epidemic of Pierce's disease has caused large losses.
      For 21 mo, we monitored adult H. coagulata at the edges of vineyards bordering
      citrus, an important crop host, natural coastal sage scrub vegetation, and
      natural riparian vegetation. We also monitored H. coagulata dispersion from 0 to
      40 m into vineyards. Finally, we examined the vertical dispersion of H. coagulata
      adults into grapevines through a season. This investigation showed that H.
      coagulata is associated with citrus, from where it disperses deep into vineyards,
      and not just the vineyard edge as with Pierce's disease vectors that are native
      to California. Peak dispersion into vineyards occurred in the summer. Another
      period of H. coagulata activity occurred in the winter in vineyards bordering
      citrus. Through the period of peak flight activity, 97% of all H. coagulata
      adults trapped between 1 and 7 m were caught at an altitude of 5 m or lower,
      suggesting the potential of a barrier as a management tactic to keep H. coagulata
      out of vineyards.

PMID- 14650509
TI  - Augmentative releases of Metaphycus sp. nr flavus against citricola scale on
      oranges in the San Joaquin Valley of California: are early releases better than
      late ones?
AB  - We conducted an augmentative release trial with the encyrtid parasitoid
      Metaphycus sp. nr flavus (Howard) against citricola scale, Coccus
      pseudomagniolarum (Kuwana), in three citrus orchards in the San Joaquin Valley of
      California. Three parasitoid release timings (14 October-13 November, 4 January-5
      February, and 26 February-16 March; hereinafter "early," "intermediate," and
      "late") were compared with a no-release check. Approximately 2,400 female
      parasitoids were released per central release tree. Late releases were associated
      with reduced scale survival on the release trees but no evidence of scale
      suppression was found on adjacent trees. Early and intermediate releases resulted
      in less pronounced scale suppression than late releases. Intermediate and late,
      but not early, releases were associated with an increase in the numbers of
      recovered female M. sp. nr flavus. Early releases, however, increased the numbers
      of recovered male Metaphycus spp. Thus, at the time of early releases, the scales
      may have been too small for the production of female parasitoids. A multiple
      regression model relating the degree of scale mortality in one orchard to the
      levels of recovered female Metaphycus helvolus (Compere), M. sp. nr flavus, or M.
      luteolus (Timberlake) (these latter two species are morphologically
      indistinguishable), and Coccophagus spp., suggested that the number of
      Coccophagus spp. females followed by M. helvolus females, were most strongly
      associated with scale mortality.

PMID- 14650510
TI  - Conserving vedalia beetle, Rodolia cardinalis (Mulsant) (Coleoptera:
      Coccinellidae), in citrus: a continuing challenge as new insecticides gain
      registration.
AB  - The effects of insecticides used for California citrus pest management were
      evaluated using larval and adult stages of vedalia beetle, Rodolia cardinalis
      (Mulsant). This predatory beetle is essential for control of cottony cushion
      scale Icerya purchasi (Williston) (Homoptera: Margarodidae) in San Joaquin Valley
      citrus. When adult beetles were exposed to treated citrus leaves, adult survival
      was significantly reduced by the foliar neonicotinoid imidacloprid and the
      pyrethroid cyfluthrin. Progeny production was significantly reduced by
      imidacloprid, cyfluthrin, fenpropathrin, and buprofezin. Buprofezin,
      pyriproxifen, and foliar imidacloprid also significantly reduced successful
      development of larvae into the adult stage. When vedalia stages were fed
      insecticide-treated cottony cushion scale reared on Pittosporum tobira (Thunb.)
      Ait, toxic effects were more severe than contact toxicity alone. Adult beetle
      survival was most profoundly reduced by the pyrethroids and to a lesser extent
      the foliar neonicotinoids acetamiprid and imidacloprid. Progeny production and
      larval development to adulthood were reduced by all insecticides but were most
      severely affected by pyriproxifen and the pyrethroids. Systemically applied
      neonicotinoids were toxic to vedalia larvae feeding on cottony cushion scale that
      had ingested these insecticides. These data demonstrate that IGRs, neonicotinoid
      insecticides, and pyrethroid insecticides have a significant, negative impact on
      vedalia beetles. Depending on the rate of insecticide used, the number and timing
      of applications, and the level of coverage of the tree, disruption of vedalia can
      be minimized. However, the situation is made difficult when pests such as citrus
      thrips Scirtothrips citri (Moulton) (Thysanoptera: Thripidae), forktailed bush
      katydid Scuddaria furcata Brunner von Wattenwyl (Orthoptera: Tettigoiniidae), or
      glassy-winged sharpshooter Homalodisca coagulata Say (Homoptera: Cicadellidae)
      require these pesticide treatments during periods of vedalia beetle activity.

PMID- 14650511
TI  - Ionizing irradiation quarantine treatment against plum curculio (Coleoptera:
      Curculionidae).
AB  - Plum curculio, Conotrachelus nenuphar (Herbst), is a quarantine pest of many
      temperate fruits, such as pomes, Malus spp.; stone fruits, Prunus spp.; and
      blueberries, Vaccinium spp.; in North America east of the Rocky Mountains and a
      small area in Utah. There are two strains, a northern univoltine one that
      undergoes obligate diapause as an adult and a southern multivoltine strain that
      usually has facultative diapause. Current quarantine treatments for shipment to
      areas that do not have the pest include methyl bromide fumigation and cold
      storage for several weeks. The cold storage treatment may not be effective
      against northern strain adults in diapause. The objective of this research was to
      develop an irradiation quarantine treatment against plum curculio. The estimated
      dose to kill southern strain plum curculio adults in one day is approximately 4
      kGy. Diapausing northern strain plum curculios were prevented from reproducing
      with 40 Gy. Reproduction of southern strain plum curculios was prevented with a
      target dose of 80 Gy, and the dose recommended as a quarantine treatment, that
      would prevent adults from reproducing, is 92 Gy, the maximum absorbed dose
      measured when a target dose of 80 Gy was sought. At that dose, oviposition may
      still occur for up to 1 wk and some of the eggs may hatch, but there is no
      development beyond the first instar. Hosts of the plum curculio would tolerate
      that dose well. Immature plum curculios were prevented from reproducing with
      lower doses.

PMID- 14650512
TI  - Feeding and foraging of wild and sterile Mediterranean fruit flies (Diptera:
      Tephritidae) in the presence of spinosad bait.
AB  - The sterile insect technique (SIT) is used to control wild Mediterranean fruit
      fly introductions in California and Florida in the U.S. In the past, bait sprays
      containing malathion proved invaluable in treating new outbreaks or large
      populations before the use of SIT. Recently, a spinosad protein bait spray, GF
      120, has been developed as a possible alternative to malathion, the standard
      insecticide in protein bait sprays. In this study, protein-deficient and protein
      fed Vienna-7 (sterile, mass-reared, "male-only" strain) flies and wild males and
      females were evaluated to determine the effectiveness of the GF-120 protein bait
      containing spinosad with respect to bait attraction, feeding, and toxicology.
      There were no effects of diet or fly type on feeding duration in small laboratory
      cages. Wild flies, however, registered more feeding events than Vienna-7 males.
      Flies that fed longer on fresh bait died faster. Protein-deficient flies were
      more active and found the bait more often than protein-fed flies. Data suggest
      that adding protein to the diet of SIT flies may decrease their response to
      baits, therefore, reduce mortality, and thus, allow the concurrent use of SIT and
      bait sprays in a management or eradication program.

PMID- 14650513
TI  - Effects of spring imidacloprid application for white grub control on parasitism
      of Japanese beetle (Coleoptera: Scarabaeidae) by Tiphia vernalis (Hymenoptera:
      Tiphiidae).
AB  - Imidacloprid, a relatively long residual neonicotinoid soil insecticide, is often
      applied to lawns and golf courses in spring for preventive control of root
      feeding white grubs. We evaluated effects of such applications on spring
      parasitism of the overwintered third-instar Japanese beetle, Popillia japonica
      Newman, by Tiphia vernalis Rohwer, an introduced solitary ectoparasitoid. Natural
      rates of parasitism on a golf course rough were significantly lower in plots
      treated with full or one-half label rates of imidacloprid in early May compared
      with untreated turf. Parasitism also was reduced when female T. vernalis were
      exposed to imidacloprid residues on turf cores in the laboratory. Such exposures
      did not affect wasp mortality, longevity, survival, or developmental period of
      Tiphia larvae feeding on hosts in treated turf. They did, however, reduce wasps'
      ability to parasitize hosts in nontreated soil for at least 1-2 wk postexposure.
      In Y-trail choice tests, wasps that previously had been exposed to treated turf
      failed to respond normally to host frass trails in the soil. Female wasps did not
      avoid imidacloprid residues, imidacloprid-treated host frass, or host grubs that
      had previously been exposed to treated soil. This study indicates that applying
      imidacloprid in early spring can interfere with biological control by T.
      vernalis, whereas postponing preventive grub treatments until June or July, after
      the wasps' flight period, will help to conserve T. vernalis populations.

PMID- 14650514
TI  - Transect sampling to enhance efficiency of corn rootworm (Coleoptera:
      Chrysomelidae) monitoring in corn.
AB  - Crop monitoring for adult corn rootworms, Diabrotica virgifera virgifera LeConte
      and Diabrotica barberi Smith and Lawrence, remains the best means to assess
      fields at risk from this pest if replanted to corn, Zea mays (L.). Improvements
      in sampling methodology, including the development of a sequential sampling plan,
      have reduced the minimum sampling time required to make a management decision to
      20 min or less per field per visit. However, many growers and crop consultants
      still find this time commitment a constraint to repeated scouting. A common
      currently used sampling method involves systematically covering most of the field
      following a "W" pattern. The feasibility of replacing the current sampling
      pattern with a simpler and less time-consuming transect (straight line) pattern
      was assessed. When sampling methods were compared, computer simulations
      demonstrated that treatment decisions based on transect sampling would have an
      acceptably low error rate averaging 10% over a range of realistic corn rootworm
      densities (0-2 adults per plant). This error rate represented a decrease in
      accuracy of <1% compared with systematic sampling. Field trials using transect,
      systematic, and random sampling in each field were used to compare the
      categorization of adult corn rootworm densities into "above" or "below" threshold
      with a sequential sampling plan. Efficiency measured in time to reach a decision,
      number of corn plants evaluated, and time divided by plants observed were
      compared between sampling methods. The three methods did not differ significantly
      in the number of plants evaluated or in the categorization of corn rootworm
      populations. Transect sampling resulted in a significantly shorter time divided
      by plants observed (38 s), than either systematic (78 s), or random sampling
      methods (166 s). Based on these results transect sampling reduces sampling time
      51% compared with systematic sampling and thus could be used to reduce total
      sampling times substantially.

PMID- 14650515
TI  - Oat cover cropping and soil insecticides in an integrated sugarbeet root maggot
      (Diptera: Otitidae) management program.
AB  - Sugarbeet, Beta vulgaris L., producers occasionally establish cereal cover crops
      to minimize early-season soil erosion, wind abrasion, and mechanical injury of
      seedlings. We evaluated the use of living oat, Avena sativa L., cover cropping as
      a cultural tactic to minimize feeding injury from sugarbeet root maggot, Tetanops
      myopaeformis (Roder), larvae at five field sites during 1996, 1998, and 1999.
      Sweep-net sampling yielded 4.8-, 11.2-, and 7.2-fold more flies from oat cover
      cropped chlorpyrifos, terbufos, and untreated control plots, respectively, than
      in noncover counterparts. However, larval feeding injury in terbufos-treated
      plots was reduced when cover-cropped (383 seeds/m2) at St. Thomas in all years. A
      reduced oat seeding rate (224 seeds/m2) also enhanced root protection in terbufos
      treated plots at St. Thomas in 1999. Less root injury was sustained in cover
      cropped chlorpyrifos plots than in noncover counterparts at St. Thomas in 2 study
      yr. Oat cover cropping also frequently resulted in reduced T. myopaeformis
      feeding injury in the absence of a soil insecticide. Although trends toward
      increased yields were often evident, significant yield benefits were limited to a
      6.8% root yield increase in oat cover plots when compared with noncover
      treatments overall at St. Thomas in 1996 and an 18.4% sucrose yield increase in
      terbufos-treated plots at St. Thomas in 1999. These findings suggest that
      beneficial interactions between planting-time soil insecticides and cereal cover
      crops are achievable in areas infested by T. myopaeformis. Demonstrated
      reductions in root feeding injury, combined with additional agronomic benefits,
      may warrant use of this production practice as part of an integrated management
      program for this key insect pest of sugarbeet.

PMID- 14650516
TI  - Overwintering of Heliothis virescens (F.) and Helicoverpa zea (Boddie)
      (Lepidoptera: Noctuidae) in cotton fields of northeast Mississippi.
AB  - Following the 1995-2001 crop seasons, population densities of pupae of tobacco
      budworm, Heliothis virescens (F.), and corn earworm, Helicoverpa zea (Boddie),
      overwintering in cotton fields, Gossypium hirsutum L., in Monroe County, MS, were
      estimated by digging a total of 43,542 m-row. Densities of pupae varied greatly
      among years with the highest densities occurring in years with low rainfall in
      the late summer and early fall. The sex ratio of pupae was variable and
      significantly male-biased in some years. The total area-wide, tobacco budworm
      population emerging from all overwintering sites was estimated from catches in
      pheromone traps whose absolute efficiency is known. After the introduction of
      Bacillus thuringiensis Berliner (Bt)-transgenic cotton in 1996 but before a
      several-fold increase in use of herbicide resistant (HR)-transgenic cotton
      cultivars in 2001, local cotton fields accounted for <2% of the total
      overwintered tobacco budworm population. In the pretransgenic cotton production
      era, it is estimated cotton fields typically accounted for <10% of the
      overwintered tobacco budworm population. Driving surveys of the tillage status of
      cotton fields and pheromone trapping to determine the timing of adult emergence
      in the spring indicate that--until the 2000 crop season--postseason tillage
      destroyed most tobacco budworm and corn earworm pupae overwintering in cotton
      fields. Adoption of HR-transgenic cultivars has quintupled cotton field area
      planted no-till, but the contribution of cotton fields to overwintered tobacco
      budworm populations has remained low. Preemptive tillage of cotton fields to kill
      overwintering tobacco budworm pupae would not appreciably suppress in-season
      population densities of this pest. However, the absence of such tillage might
      increase the rate at which the tobacco budworm develops resistance to
      insecticides and counteradaptation to antibiotic host plant resistance traits
      including the Bt-transgenic trait.

PMID- 14650517
TI  - The cost of slowing the spread of the gypsy moth (Lepidoptera: Lymantriidae).
AB  - Beginning in 1992, the Slow The Spread (STS) pilot project was initiated to
      target gypsy moth (Lymantria dispar L.) spread rate reduction by controlling
      populations in the transition zone. The project uses intensive monitoring
      techniques, with pheromone-baited sticky moth traps, to detect low-level
      populations and target them for eradication. The primary objective of the pilot
      project was to evaluate the feasibility of using integrated pest management
      techniques to slow the spread of gypsy moths over a large geographical area. In
      this study, the cost of STS pilot project activities in 1993-1995 was
      investigated. A cost accounting system was developed and used as a framework to
      collect the cost data and to investigate cost patterns and characteristics. Total
      expenditures of STS activities for 1993-1995 were 7,685.2 million dollars. Per
      unit cost was 49.67 dollars per trap with the direct cost component being 35.03
      dollars per trap. Trapper labor and vehicle expense accounted for approximately
      90% of this direct cost. Per unit cost for treatment activities was found to
      average 27.86 dollars per treated acre. In general, the STS pilot project is
      labor intensive, specifically the trapping component. From 1993-1995, 59% of
      total project expenditures were spent on trapping activities, 28% on pesticide
      treatments, and 13% on data management. A trapper productivity rate regression
      model is described.

PMID- 14650518
TI  - Evaluation of systemic insecticides as a treatment option in integrated pest
      management of the elm leaf beetle, Xanthogaleruca luteola (Muller) (Coleoptera:
      Chrysomelidae).
AB  - This study evaluates the efficacy of two systemic insecticides (imidacloprid and
      abamectin) in an operational setting and their suitability to be incorporated
      into an integrated pest management program. Elm leaf beetle abundance and leaf
      damage were compared between treated trees and untreated control trees from 1995
      through 1999. Laboratory bioassays using first-instar larvae were also used to
      measure the toxicity of leaves collected from treated trees at varying times
      after treatment. Trunk injections of abamectin and imidacloprid reduced the
      defoliation caused by elm leaf beetle when applied after monitoring at the peak
      density of elm leaf beetle eggs. Treatment in the first generation appeared to
      provide protection against damage in that generation as well as the second and
      third beetle generations. Both of these materials become active within the tree
      canopy very quickly and are therefore compatible with a management program that
      determines the need for treatment based on monitoring for egg clusters at peak
      density of eggs. Laboratory bioassays showed no toxicity of leaves in the year
      following treatment.

PMID- 14650519
TI  - Field and laboratory tests of new insecticides against the apple maggot,
      Rhagoletis pomonella (Walsh) (Diptera: Tephritidae).
AB  - Laboratory bioassays and field tests were conducted to compare the effectiveness
      of the new insecticides, imidacloprid, indoxacarb, pyriproxyfen, spinosad,
      thiacloprid, and thiamethoxam, against apple maggot. The activity ranking of the
      compounds in reducing oviposition in laboratory bioassays was: imidacloprid, 95%
      reduction at 11 ppm > thiamethoxam, 91% and thiacloprid, 89% reduction at 100 ppm
      > spinosad, 98% reduction at 316 ppm > indoxacarb, 80% reduction at 1000 ppm >
      pyriproxyfen, 0% reduction at 38 ppm. In laboratory bioassays, the only
      insecticides that were toxic to flies at concentrations equal to or below the
      recommended field rates were imidacloprid, (50% of flies at 11 ppm), spinosad
      (90% of flies at rates > 10 ppm), and thiamethoxam (approximately 50% of flies at
      32 ppm). In field trials, thiacloprid was the only material that consistently
      controlled apple maggot fruit infestation that was comparable to standard
      treatments of organophosphate insecticides. Spinosad applied at weekly intervals,
      and indoxacarb applied as biweekly sprays provided adequate control of apple
      maggot damage when infestation levels in the field were low, but were not
      effective in preventing damage in small plots when apple maggot pressure was
      high.

PMID- 14650520
TI  - Estimation of production losses caused by the coffee berry borer (Coleoptera:
      Scolytidae) and calculation of an economic damage threshold in Togolese coffee
      plots.
AB  - The coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Scolytidae),
      which exists in all coffee producing zones, is a major pest. The seriousness of
      this scolytid was assessed in Togolese plots spread over five agroclimatic zones,
      by determining the attack rate from a sample of coffee trees. The work was
      carried out over 2 yr and revealed that weight losses were proportional to the
      attack rates. The average infestation rates were 5.64% in the first year and
      6.36% in the second year, while total production losses amounted to 2.60% and
      3.18%, respectively, for the same periods. Generally speaking, attack rates in
      the plots were low and varied considerably within a given zone. Plantations
      located on plateau were more severely attacked than those in the plains. A
      relationship was established between total losses and the cost of insecticide
      treatment; this relationship was used to calculate an economic damage threshold
      beyond which control proves to be cost effective.

PMID- 14650521
TI  - Toxicity of plant essential oils to Trialeurodes vaporariorum (Homoptera:
      Aleyrodidae).
AB  - A total of 53 plant essential oils were tested for their insecticidal activities
      against eggs, nymphs, and adults of Trialeurodes vaporariorum Westwood, using an
      impregnated filter paper bioassays without allowing direct contact. Responses
      varied according to oil type and dose, and developmental stage of the insect.
      Bay, caraway seed, clove leaf, lemon eucalyptus, lime dis 5 F, pennyroyal,
      peppermint, rosewood, spearmint, and tea tree oils were highly effective against
      T. vaporariorum adults, nymphs, and eggs at 0.0023, 0.0093, and 0.0047 microl/ml
      air, respectively. These results indicate that the mode of delivery of these
      essential oils was largely a result of action in the vapor phase. Significant
      correlations among adulticidal, nymphicidal, and ovicidal activities of the test
      oils were observed. The essential oils described herein merit further study as
      potential fumigants for T. vaporariorum control.

PMID- 14650522
TI  - Effectiveness of GF-120 fruit fly bait spray applied to border area plants for
      control of melon flies (Diptera: Tephritidae).
AB  - In a field study in Hawaii, color-marked protein-deprived and protein-fed female
      melon flies, Bactrocera cucurbitae Coquillett, were released within canopies of
      unsprayed sorghum plants (a nonhost of melon flies) outside of a border area of
      unsprayed or bait-sprayed sorghum plants or open space that surrounded cucumbers,
      a favored host of melon flies. Application of bait spray to sorghum or sugarcane
      surrounding host plants of melon flies is a common practice for melon fly control
      in Hawaii. GF-120 Fruit Fly Bait spray proved very effective in preventing
      protein-deprived females from alighting on cucumbers (23% of released females
      were observed dead on bait-sprayed sorghum; 0% were observed alive on cucumbers),
      but proved less effective in suppressing protein-fed females (14% of released
      females were observed dead on bait-sprayed sorghum; 11% were observed alive on
      cucumbers). No females were found dead on unsprayed sorghum. Compared with open
      space surrounding cucumbers, the presence of unsprayed sorghum as surrounding
      border area neither significantly enhanced nor significantly inhibited the
      ability of either type of female with respect to finding cucumbers. Greenhouse
      cage assays revealed that compared with droplets of water, droplets of GF-120
      Fruit Fly Bait spray were highly attractive to protein-deprived females within 1
      h of bait spray application to sorghum, but lost about half of their
      attractiveness within 5 h and all of it within 24 h under the dry greenhouse
      conditions used for maintaining baited-sprayed sorghum plants in these assays.
      Laboratory cup assays showed that bait spray droplets remained highly toxic to
      protein-deprived females 24 h after application, but lost nearly half of their
      toxicity within 4 d under laboratory exposure and nearly all of it after
      approximately 8 mm of rainfall. Combined findings suggest that application of GF
      120 Fruit Fly Bait spray to nonhost plants for melon fly control either be made
      often enough to overcome loss of attractiveness of bait spray droplets to females
      or that bait spray be applied to nonhost plants that are themselves attractive to
      the females.

PMID- 14650523
TI  - Cyromazine seed treatments to control onion maggot, Delia antiqua, on green
      onions.
AB  - Cyromazine seed treatments were evaluated for onion maggot control in green onion
      crops. The more tolerant to organophosphates of two populations of onion maggots
      was chosen for further research, based on the results of adult assays in a Potter
      spray tower. In the laboratory, first-instar mortality was compared between film
      coated seed treatment and soil drench treatment. The LC50 for the film-coated
      seed treatment was approximately one fourth that of the soil drench treatment. In
      choice assays, no significant difference was observed between the number of eggs
      deposited on seedlings grown from film-coated seeds with cyromazine and film
      coated seeds without cyromazine. Field studies demonstrated that all rates of
      cyromazine seed treatment resulted in protection of onion plants from onion
      maggot damage. Green onions may not require as high a rate of cyromazine for
      control of onion maggots as the rate established for use in dry onions for two
      reasons: the seeding rate is much higher for green onions resulting in more AI/ha
      for a given amount of AI/kg of seed, and a given percentage of stand loss is more
      difficult to detect in green onions than in dry onions.

PMID- 14650524
TI  - Comparison of economic and plant phenology-based thresholds for management of
      Lygus lineolaris (Hemiptera: Miridae) in Minnesota strawberries.
AB  - Field studies were conducted in southeastern Minnesota, 2000-2002, to assess
      damage potential and management options for adult Lygus lineolaris (Palisot de
      Beauvois) in June-bearing strawberries (Fragaria x ananassa). The first study was
      designed to assess the efficacy of a published economic threshold for L.
      lineolaris nymphs compared with a plant phenology-based threshold management
      program, targeted at L. lineolaris adults. L. lineolaris nymphs were sampled
      using the standard white pan beat method; adults were sampled using yellow sticky
      traps. In the second study, during 2001-2002, caged strawberries were
      artificially infested with adult L. lineolaris at specific plant growth stages
      (i.e., vegetative, green bud, white bud, first blossom, peak blossom, first green
      fruit, and first ripe fruit) to determine the most susceptible growth stages of
      strawberry. The phenology-based thresholds proved to be more effective in
      managing L. lineolaris than the current economic threshold based on nymphs.
      Results from the infestation timing study indicate that early-growth stages
      (i.e., green and white bud) are most susceptible to adult L. lineolaris feeding
      damage. During the early-growth stages, only L. lineolaris adults were present;
      infestations of nymphs occurred primarily from first blossom to green berry.
      Results from both studies indicate that (1) management of adult L. lineolaris
      during the early strawberry growth stages is recommended for maximizing
      marketable yield and (2) the use of plant phenology-based thresholds, when adults
      are present, will significantly improve insecticide spray timing, and thus
      minimize the number of insecticide sprays.

PMID- 14650525
TI  - Honey bee (Hymenoptera: Apidae) foraging in response to preconditioning with
      onion flower scent compounds.
AB  - Onion (Allium cepa L.) seed production has long been plagued with yield problems
      because of lack of pollination by the honey bee, Apis mellifera L. To attempt to
      attract more pollinators to the onion seed production field, honey bees were
      conditioned to associate onion floral odor components with a reward. Isolated
      nucleus hives of honey bees were fed 30% sucrose solutions scented with a 0.2%
      solution of onion floral odor compounds. After feeding on these solutions for 6
      wk, bees were not found to prefer onion flowers to two competing food sources,
      carrot and alfalfa flowers, at the 5% significance level. However, there was an
      overall trend indicating a change in honey bee behavior, with fewer "trained"
      bees visiting alfalfa and carrot and more visiting onion. Thus, it may be
      possible to alter honey bee behavior with preconditioning but probably not to a
      degree that would be economically significant.

PMID- 14650526
TI  - Identification of Reticulitermes spp. (Isoptera: Reticulitermatidae) from south
      central United States by PCR-RFLP.
AB  - Because of morphological ambiguity, traditional identification of Reticulitermes
      Holmgren termites has always been difficult and unreliable. A molecular
      diagnostic method is presented for differentiating Reticulitermes species
      occurring in the south central United States, which are economically important
      urban pests. A 379-bp region of the mtDNA COII gene and a 415-bp region of the
      mtDNA 16S rRNA gene were amplified using polymerase chain reaction (PCR) and
      sequenced from Reticulitermes flavipes (Kollar), Reticulitermes virginicus
      (Banks), Reticulitermes hageni Banks, and Reticulitermes tibialis (Banks).
      Applying DNA sequence data, the PCR-restriction fragment length polymorphism (PCR
      RFLP) analysis of two restriction enzymes each for the COII amplicon and the 16S
      amplicon, were diagnostic for all of the Reticulitermes species analyzed. Based
      on putative mutation rates, >87% and 97% of the samples should be successfully
      identified to species with PCR-RFLP of COII and 16S, respectively. To verify the
      accuracy of our predictions, we examined unclassified Reticultermes populations
      from Arkansas, Louisiana, Missouri, Oklahoma, Texas, and Virginia using PCR-RFLP.
      Applying PCR-RFLP, 97 samples were correctly classified to species. This
      technique allows the use of field-collected specimens preserved in alcohol and
      can identify termite specimens regardless of caste. PCR-RFLP, resolved with
      agarose or polyacrylamide gel electrophoresis, provided an efficient method for
      identification of Reticulitermes species from the south central United States for
      diagnostic purposes.

PMID- 14650527
TI  - Targeted versus standard bait station placement affects subterranean termite
      (Isoptera: Rhinotermitidae) infestation rates.
AB  - A major challenge to termite baiting in soil habitats is the prolonged time that
      it may take for subterranean termites (Isoptera: Rhinotermitidae) to infest
      stations. The objective of this research study was to determine whether the
      location of food sources (Sentricon in-ground monitoring stations and wooden
      monitors) influences the likelihood of infestation by termites. In field trials
      conducted at 15 structures in central Ohio, standard placement of stations at 3
      4.5 m intervals was compared with targeted placements based on evidence of
      termite activity indoors and outdoors as well as conducive moisture conditions.
      Termites infested significantly more targeted placements (70/374) than standard
      placements (35/372) around structures. At the targeted placement sites, termites
      infested more wooden monitors than Sentricon stations, but this was not
      statistically significant. This implies that placement, rather than cellulose
      composition, was the more important factor. Termites first infested
      stations/monitors an average of 38 d sooner at targeted sites than standard
      placement sites. This research indicates that evidence of termite activity
      indoors and outdoors should be a prime consideration when placing in-ground
      stations.

PMID- 14650528
TI  - Resistance of insecticide-treated foam board insulation against the eastern
      subterranean termite and the Formosan subterranean termite (Isoptera:
      Rhinotermitidae).
AB  - Three foam board types, one untreated control, one containing 2,000 ppm disodium
      octaborate tetrahydrate (DOT), and one containing 1,000 ppm deltamethrin, were
      exposed to field populations of the eastern subterranean termite, Reticulitermes
      flavipes (Kollar), and the Formosan subterranean termite, Coptotermes formosanus
      Shiraki. There was no significant difference in termite damage between foam
      boards treated with 2,000 ppm DOT and the untreated control. Form boards
      containing 1,000 ppm deltamethrin were not damaged by R. flavipes, whereas only
      minor damage occurred after exposure to C. formosanus.

PMID- 14650529
TI  - A spatially explicit model simulating western corn rootworm (Coleoptera:
      Chrysomelidae) adaptation to insect-resistant maize.
AB  - A stochastic spatially explicit computer model is described that simulates the
      adaptation by western corn rootworm, Diabrotica virgifera virgifera LeConte, to
      rootworm-resistance traits in maize. The model reflects the ecology of the
      rootworm in much of the corn belt of the United States. It includes functions for
      crop development, egg and larval mortality, adult emergence, mating, egg laying,
      mortality and dispersal, and alternative methods of rootworm control, to simulate
      the population dynamics of the rootworm. Adaptation to the resistance trait is
      assumed to be controlled by a monogenic diallelic locus, whereby the allele for
      adaptation varies from incompletely recessive to incompletely dominant, depending
      on the efficacy of the resistance trait. The model was used to compare the rate
      at which the adaptation allele spread through the population under different
      nonresistant maize refuge deployment scenarios, and under different levels of
      crop resistance. For a given refuge size, the model indicated that placing the
      nonresistant refuge in a block within a rootworm-resistant field would be likely
      to delay rootworm adaptation rather longer than planting the refuge in separate
      fields in varying locations. If a portion of the refuge were to be planted in the
      same fields or in-field blocks each year, rootworm adaptation would be delayed
      substantially. Rootworm adaptation rates are also predicted to be greatly
      affected by the level of crop resistance, because of the expectation of
      dependence of functional dominance on dose. If the dose of the insecticidal
      protein in the maize is sufficiently high to kill >90% of heterozygotes and
      approximately 100% of susceptible homozygotes, the trait is predicted to be much
      more durable than if the dose is lower. A partial sensitivity analysis showed
      that parameters relating to adult dispersal affected the rate of pest adaptation.
      Partial validation of the model was achieved by comparing output of the model
      with field data on population dynamics, and with field data documenting rootworm
      adaptation to cyclodienes and organophosphates.

PMID- 14650530
TI  - Origin and extent of resistance to fipronil in the German cockroach, Blattella
      germanica (L.) (Dictyoptera: Blattellidae).
AB  - Fipronil, a phenylpyrazole insecticide, was made available in 1999 in bait
      formulations for use against the German cockroach, Blattella germanica (L.). We
      have investigated resistance to fipronil in the descendants of cockroaches
      collected just before, or contemporaneously with, the introduction of fipronil
      baits. Cockroaches were obtained in two types of settings: homes that either had
      or had not been serviced by a pest management professional while occupied by
      their current residents. Thorough inspections by us turned up no evidence that
      fipronil had been used in any of the homes, and in addition, no residents claimed
      to have used baits containing fipronil. Resistance to fipronil was detected by
      topically dosing adult males with the LC99 of fipronil, the value of which was
      determined in a dose-response assay with males of an insecticide-susceptible
      strain. Fewer than 99 of 100 males of all field-collected strains died within 72
      h of being treated. Moreover, substantial numbers of males survived doses three
      and 10-fold greater than the LC99. Regression analysis showed that 67% of the
      variation in the percentage of males that died after being treated with fipronil
      was explained by a linear relationship with the percentage that died after being
      treated with dieldrin. Therefore, it appears that resistance to fipronil in
      German cockroaches--whose ancestors had never been exposed to it--is attributable
      to enduring resistance to the cyclodienes, which were formerly used for cockroach
      control and have a similar mode of action as fipronil. Lastly, we found that
      insects resistant to topically administered fipronil were likewise resistant, and
      to a similar degree, to ingested fipronil.

PMID- 14650531
TI  - Boric acid bait kills adult mosquitoes (Diptera: Culicidae).
AB  - The toxicity of boric acid solutions to adult Anopheles quadrimaculatus Say,
      Culex nigripalpus Theobald, and Aedes albopictus Skuse was evaluated in the
      laboratory. Median lethal concentrations (LC50 in %) at 24-h exposure for male
      and female An. quadrimaculatus were 0.317 and 0.885, respectively; for Cx.
      nigripalpus, 0.273 and 0.560, respectively; and for Ae. albopictus, 0.174 and
      0.527, respectively. The LC50 values at 48-h exposure for male and female An.
      quadrimaculatus were 0.101 and 0.395, respectively; for Cx. nigripalpus, 0.098
      and 0.255, respectively; and for Ae. albopictus, 0.078 and 0.244, respectively.
      In laboratory tests, access for 48 h to sucrose (10%) water containing 1% boric
      acid (boric acid bait) resulted in 98% mortality in blood fed, gravid, and parous
      Ae. albopictus. When offered a choice between boric acid bait and sucrose water,
      52% of male and 33% of female Ae. albopictus ingested sufficient boric acid bait
      in 24 h to cause death; after 48 h, respective percent mortalities were 88 and
      58%. In outdoor tests, in a walk-in screened cage (156 m3) containing 1,250
      female Ae. albopictus, mosquito biting rates on the exposed forearm of a human
      subject in 3-min exposure were reduced > or = 78% for the boric acid bait
      treatment, compared with a sucrose water control.

PMID- 14650532
TI  - Relationship between maize stem structural characteristics and resistance to pink
      stem borer (Lepidoptera: Noctuidae) attack.
AB  - The pink stem borer, Sesamia nonagrioides (Lefebvre), is one of the most
      important insect pests of maize (Zea mays L.) in northwestern Spain. The
      objectives of this work were to evaluate, at different times during the growth of
      maize, structural traits related to the entry point and tissues on which larvae
      feed and to determine the relationship between these structural traits and the
      stem borer resistance. Six inbred lines with different levels of stem resistance
      to S. nonagrioides were evaluated in several trials. Potential structural
      resistance factors included rind and pith puncture resistance (RPR and PPR), rind
      thickness, length of the meristematic area (LMA), and pith parenchyma interlumen
      thickness (PPIT). Surprisingly, the inbred lines that showed the strongest
      stalks, EP42 and EP47, were not stem resistant to pink stem borer attack, while
      the stem resistant inbreds A509, CM151, and PB130 were among the least resistant
      to rind puncture. There were no significant differences among resistant and
      susceptible inbreds for the rind thickness. However, the susceptible inbred EP42
      had the softest internode pith, and the resistant inbred PB130 showed the
      hardest, as was expected. Susceptible inbred lines in general showed higher
      values for the LMA, while the PPIT was important for individual inbreds. The
      results suggest that the usefulness of these characters as estimators of pink
      stem borer resistance is limited to some genotypes. Besides, even among those
      genotypes, other mechanisms of resistance that do not involve stalk strength
      could be present. Among the traits considered, the LMA was the most promising as
      an indicator of resistance to pink stem borer, although further experimentation
      is necessary.

PMID- 14650533
TI  - Resistance to greenbug (Heteroptera: Aphididae) biotype I in Aegilops tauschii
      synthetic wheats.
AB  - The greenbug, Schizaphis graminum (Rondani), is a major pest of wheat in North
      America, reducing U.S. wheat production by 60 to 100 million dollars each year.
      In this research, 149 wheat lines containing genes from Aegilops tauschii (Coss.)
      Schmal. were evaluated for resistance to greenbug biotype I. More than 50% of the
      lines sustained moderate foliar chlorosis from greenbug feeding, and
      approximately one third of all the lines were highly resistant. All lines with
      chlorosis scores similar to the resistant control 'Largo' expressed high levels
      of antibiosis, producing greenbug populations with mean weights ranging from 0.05
      to 11.8 mg. There was no significant difference between greenbug weights on these
      lines and those reared on 'Largo', but the mean weight of individuals reared on
      the susceptible control 'Thunderbird' was significantly greater than those reared
      on 'Largo' or any of the test lines. The mean population size of greenbugs
      produced on plants of each line was significantly correlated with mean greenbug
      weight. Tolerance was not evident in any of the lines examined, but was
      unexpectedly apparent in 'Thunderbird' at a level similar to that in the tolerant
      control cultivar 'Largo'.

PMID- 14650534
TI  - Antixenosis and antibiosis of common beans to Thrips palmi Karny (Thysanoptera:
      Thripidae).
AB  - Antixenosis and antibiosis in the resistance of common beans (Phaseolus vulgaris
      L.) to the melon thrips, Thrips palmi Karny, were investigated under laboratory
      and field conditions. Experiments were conducted for four moderately resistant
      genotypes ('Brunca', BH-130, EMP 486, and FEB 115) in comparison with one
      susceptible genotype (APN 18). Multiple-choice tests recorded most thrips on EMP
      486 and least on FEB 115. Dual-choice tests conducted in both laboratory and
      field confirmed the antixenotic effect of FEB 115 and the attractant effect of
      EMP 486 on thrips. These results demonstrate the significance of antixenosis in
      the resistance of common beans to T. palmi. Life-table studies showed significant
      differences in egg duration, immature and adult survivorship, female body length
      and longevity, daily oviposition rate, and total fecundity among the bean
      genotypes. The intrinsic rate of natural increase (r(m)) and its associated
      population parameters varied significantly with the bean genotype on which T.
      palmi cohorts were reared. Based on mean r(m) values, the five bean genotypes can
      be divided into two groups, with BH-130 and 'Brunca' being less favorable for the
      population growth of thrips than EMP 486 and FEB 115; the latter were comparable
      to the susceptible genotype APN 18. These life-table results indicate the role of
      antibiosis in enhancing the resistance of common beans to T. palmi.

PMID- 14650535
TI  - Fixed precision sequential sampling plans for the greenbug and bird cherry-oat
      aphid (Homoptera: Aphididae) in winter wheat.
AB  - The numbers of greenbugs, Schizaphis graminum (Rondani), and bird cherry-oat
      aphids, Rhopalosiphum padi L., per wheat tiller (stem) were estimated in 189
      production winter wheat (Triticum aestivum L.) fields located throughout
      Oklahoma. Taylor's power law regressions were calculated from these data and used
      to construct fixed precision sequential sampling schemes for each species. An
      evaluation data set was constructed from 240 samples taken during three growing
      seasons from winter wheat fields at four locations in Oklahoma. Wheat cultivar
      and growth stage were recorded for each field on the day of sampling. Taylor's
      power law parameters for evaluation fields differed significantly for both
      species among growing seasons, locations, and plant growth stages. Median
      precision achieved using the fixed precision sequential sampling schemes for each
      species departed <20% from expected precision over the range population intensity
      in the evaluation data. For the 10% of samples with greatest deviation between
      observed and expected precision, observed precision was 13.8-81.8% greater than
      that expected precision depending on aphid species and population intensity. For
      the greenbug, the distribution of the percentage deviation between observed and
      expected precision was positively skewed, so that the sampling scheme tended to
      over-predict precision. For the bird cherry-oat aphid, the distribution was more
      symmetric. Even though precision observed using the sampling schemes frequently
      varied from expected precision, because of the inevitable consequence of sampling
      error and environmental variation, the sampling schemes yielded median observed
      precision levels close to expected precision levels over a broad range of
      population intensity.

PMID- 14650536
TI  - Bioactivities of l-carvone, d-carvone, and dihydrocarvone toward three stored
      product beetles.
AB  - The rice weevil, Sitophilus oryzae L., adults were highly susceptible by contact
      to l-carvone, d-carvone, and dihydrocarvone when compared with the lesser grain
      borer, Rhyzopertha dominica F., adults and red flour beetle, Tribolium castaneum
      (Herbst.). Adults of R. dominica were more susceptible than the other species to
      fumigant vapors of l-carvone, d-carvone, and dihydrocarvone. The three larval
      stages (14-, 16-, and 18-d-old) of T. castaneum progressively became more
      susceptible with age toward contact toxicity of three test compounds but in
      fumigant toxicity, 16-d-old larvae of T. castaneum were more susceptible to the
      three compounds. Comparison of contact and fumigant toxicity of the test
      compounds indicates that l-carvone and d-carvone possess 24 times more fumigant
      toxicity toward adults of R. dominica than its contact toxicity. Overall order of
      toxicity was l-carvone > d-carvone > dihydrocarvone. Egg hatching and subsequent
      larval and adult survival of T. castaneum were significantly reduced when the
      eggs of T. castaneum were treated with l-carvone, d-carvone, and dihydrocarvone.
      l-Carvone completely suppressed egg hatching at the concentration of 7.72 mg/cm2.
      Data on feeding-deterrent indices indicate the high potency of l-carvone as
      feeding-deterrent in order of S. oryzae adults > T. castaneum adults > R.
      dominica adults > T. castaneum larvae.

PMID- 14650537
TI  - Evaluation of three formulations of Beauveria bassiana for control of lesser
      mealworm and hide beetle in Georgia poultry houses.
AB  - Initial screening of 12 Beauveria bassiana (Balsamo) Vuillemin isolates against
      larvae of the lesser mealworm (Alphitobius diaperinus [Panzer]) resulted in the
      selection of two isolates, GHA and 707, for further testing under field
      conditions. Three formulations of each strain were prepared: an EC, a ground corn
      granular formulation, and waste product of fungal propagation containing spent
      media, mycelia, and unharvested conidia ("residue" formulation). Two field trials
      were conducted in commercial caged-layer houses in Georgia with 5-6 mo of manure
      accumulation and established populations of A. diaperinus and hide beetles
      (Dermestes maculatus DeGeer). In the first trial field, B. bassiana was applied a
      single time to the manure surface at either 10(9) (EC and granular cornmeal bait
      formulations) or 10(8) (residue formulation) fungal spores per square meter. In
      the second trial, two successive weekly treatments were applied, using a total of
      6x the rate of application used in the first trial, Significant treatment effects
      were short-lived and only detected 2 wk after treatment in both trials. The
      granular formulations of both strains and the residue formulation of the GHA
      strain provided the greatest degree of suppression (60-90%) of beetle larvae. A
      laboratory bioassay confirmed that the granular bait was the most effective
      formulation. More frequent applications made earlier in the manure accumulation
      cycle may be necessary to achieve satisfactory control of these beetles.

PMID- 14650538
TI  - Efficacy of the ivomec SR bolus for control of horn flies (Diptera: Muscidae) on
      cattle in South Texas.
AB  - The concentration of ivermectin in the serum of Hereford heifers treated with a
      single Ivomec SR bolus reached a maximum of 8.8 +/- 0.9 ppb at 2 wk post
      treatment. The single bolus treatment resulted in <10% mortality of adult horn
      flies feeding on the blood of the treated animals over the 21-wk trial. Bioassays
      of the manure from treated cattle showed complete inhibition of development of
      immature horn flies through week 19 post-treatment. When the trial was repeated
      using two Ivomec SR boluses/heifer, the concentration of ivermectin in the serum
      of the treated cattle reached a maximum level of 31.2 +/- 3.9 ppb at week 13 post
      treatment. During the first 17 wk of treatment, the use of two boluses/heifer
      resulted in 96.2 and 81.2% mortality of adult male and female horn flies feeding
      on the blood of treated animals, respectively. From these studies, we conclude
      that a single Ivomec SR bolus used as an anthelmintic treatment can be expected
      to provide significant control of immature horn flies developing in the manure,
      but not of adults feeding on the treated cattle.

PMID- 14650539
TI  - Effect of horn fly (Haematobia irritans) control on growth and reproduction of
      beef heifers.
AB  - The influence of horn fly control with commercially available ear tags was
      studied on beef replacement heifers (n = 670) for growth and reproductive
      performance. The study was conducted at five sites in Louisiana over 3 yr.
      Heifers used were yearling replacement females that were exposed to fertile bulls
      during a limited spring breeding season that coincided with the horn fly season.
      In mid to late May of each year, heifers were randomly assigned to one of two
      horn fly treatments: untreated and treated for horn fly control. The trial
      continued each year until September or October at the end of fly season.
      Pregnancy status was determined by rectal palpation. Horn fly populations were
      controlled on the treated heifers at moderate levels (84%). Total weight gain of
      treated heifers was 14% greater than for untreated heifers. Horn fly treatment
      had no effect on pregnancy rate (78% and 75% for untreated and treated heifers,
      respectively). Treatment differences for weight gain were of greater magnitude
      for heifers failing to conceive than for heifers that became pregnant. Weight
      gains of nonpregnant treated heifers were 33% greater than for nonpregnant
      untreated heifers, whereas weight gains of pregnant treated heifers were 8%
      greater than for pregnant untreated heifers. In conclusion, horn fly control on
      yearling beef replacement heifers improved weight gain but had no effect on first
      exposure reproduction.

PMID- 14650540
TI  - Heat resistance in liquids of Enterococcus spp., Listeria spp., Escherichia coli,
      Yersinia enterocolitica, Salmonella spp. and Campylobacter spp.
AB  - The aim of the work was to collect, evaluate, summarize and compare heat
      resistance data reported for Campylobacter, Enterococcus, Escherichia, Listeria,
      Salmonella and Yersinia spp. The work was limited to resistance in liquids with
      pH values 6-8. Results obtained under similar experimental conditions were
      sought. Thermal destruction lines for the various bacterial groups studied were
      constructed using log10 D values and treatment temperatures. There was a good
      linear relationship between log10 D and temperature with Escherichia coli,
      listerias and salmonellas. For campylobacters, enterococci and yersinias the
      relationships were weaker but, nevertheless, present. Using the slopes of the
      lines and their 95% confidence limits, z values and their 95% confidence limits
      were calculated. z values were compared with z values obtained from reports. The
      equations for the lines were also used for calculation of predicted means of D
      values at various treatment temperatures. 95% confidence limits on predicted
      means of D values and on predicted individual D values were also calculated.
      Lines and values are shown in figures and tables. Differences in heat resistance
      noted between and within the bacterial groups studied are discussed.

PMID- 14650541
TI  - Endocrine measurements and calving performance of Swedish red and white and
      Swedish Holstein dairy cattle with special respect to stillbirth.
AB  - During 3 consecutive calving seasons, calving performance, placental
      characteristics and endocrine profiles of total 98 pregnancies of late pregnant
      Swedish Red and White (SRB) and Swedish Holstein (SLB) dairy heifers and cows,
      were investigated. Ninety-four singleton pregnancies and 4 sets of twins were
      recorded. In animals with singleton pregnancy, 8 stillbirths, 7 weak calves, 3
      premature parturitions and 1 abortion were registered. In the SLB heifers, 19% of
      stillbirth (5/26) were observed, while 5% (2/42) were noted for the SRB heifers.
      One stillborn calf derived from the SRB cows and none was found from the SLB
      cows. In the heifers and cows delivering a normal living calf with unassisted
      parturition, the placentome thickness monitored by ultrasonography was constant
      towards the end of pregnancy. The numbers of foetal cotyledons varied
      individually between animals but in total, fewer cotyledons were found in the
      foetal membranes of the SRB animals than in the SLB animals (69 +/- 19) vs. (88
      +/- 29) (p < 0.05). No morphological and numerical differences of the placentome
      thickness in animals delivering a stillborn or weak calf, compared to animals
      delivering a normal living calf, could be observed. In animals with unassisted
      parturition and without birth complications, the levels of progesterone (P4),
      PGF2alpha metabolite (PG-metabolite), cortisol, oestrone sulphate (E1SO4) and
      pregnancy associated glycoproteins (PAGs) were not different by breeds and
      parities. In animals carrying stillbirth, higher levels of E1SO4 were found in 3
      SRB animals and 1 SLB heifer, whereas lower levels of E1SO4 were recorded in 3
      SLB heifers during the last week of pregnancy, compared to the profiles found in
      animals with unassisted parturition. Additionally, the levels of PAGs remained
      low and constant in 1 SRB cow (delivering a stillborn calf), 1 SRB heifer (giving
      birth prematurely), 4 animals (carrying twins) and 1 aborting SRB cow. Our
      results show a very high rate of stillbirth in especially SLB heifers and
      deviating profiles of E1SO4 and PAGs in animals with impaired parturition were
      recorded.

PMID- 14650542
TI  - Antibacterial effect of bovine lactoferrin against udder pathogens.
AB  - The antibacterial effect of lactoferrin (Lf) was tested on isolates of
      Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and coagulase
      negative staphylococci (CNS) as well as on Pseudomonas aeruginosa (P. aeruginosa)
      and Klebsiella pneumoniae (K. pneumoniae), originally isolated from bovine
      mastitis. Concentrations of Lf used were 0.67 mg/ml, 1.67 mg/ml, and 2.67 mg/ml.
      Growth of udder pathogens was monitored by turbidometry either in broth culture
      or in whey prepared from normal milk. We focused on 3 different growth variables:
      lag time, slope, and maximum absorbance of bacterial growth curves. Growth
      inhibition was seen in the broth but hardly at all in whey. The isolates of E.
      coli and CNS did not grow sufficiently well in whey to draw any conclusions. The
      most effective inhibitory activity of Lf was seen against E. coli and P.
      aeruginosa. All 5 E. coil isolates had similar growth patterns. Inhibition of
      growth by Lf was concentration-dependent. The concentration of 0.67 mg/ml in
      broth and whey was generally too low for a significant inhibitory effect.

PMID- 14650543
TI  - Verotoxinogenic Escherichia coli (VTEC) O157:H7--a nationwide Swedish survey of
      bovine faeces.
AB  - In the autumn of 1995 the first outbreaks of enterohemorrhagic Escherichia coli
      O157:H7 including ca 100 human cases were reported in Sweden. From outbreaks in
      other countries it is known that cattle may carry these bacteria and in many
      cases is the source of infection. Therefore, the present study was performed to
      survey the Swedish bovine population for the presence of verotoxin-producing E.
      coli (VTEC) of serotype O157:H7. Individual faecal samples were collected at the
      16 main Swedish abattoirs from April 1996 to August 1997. Of 3071 faecal samples,
      VTEC O157 were found in 37 samples indicating a prevalence of 1.2% (CI95% 0.8
      1.6). All 37 isolates carried genes encoding for verotoxin (VTI and/or VT2),
      intimin, EHEC-haemolysin and flagellin H7 as determined by PCR. Another 3 strains
      were of serotype O157:H7 but did not produce verotoxins. The 37 VTEC O157:H7
      strains were further characterised by phage typing and pulsed-field gel
      electrophoresis. The results clearly show that VTEC O157:H7 is established in the
      Swedish bovine population and indicate that the prevalence of cattle carrying
      VTEC O157:H7 is correlated to the overall geographical distribution of cattle in
      Sweden. Results of this study have formed the basis for specific measures
      recommended to Swedish cattle farmers, and furthermore, a permanent monitoring
      programme was launched for VTEC O157:H7 in Swedish cattle at slaughter.

PMID- 14650544
TI  - Efficacy of targeted 5-day combined parenteral and intramammary treatment of
      clinical mastitis caused by penicillin-susceptible or penicillin-resistant
      Staphylococcus aureus.
AB  - Combined parenteral and intramammary treatment of mastitis caused by
      Staphylococcus aureus was compared to parenteral treatment only. Cows with
      clinical mastitis (166 mastitic quarters) caused by S. aureus treated by
      veterinarians of the Ambulatory Clinic of the Faculty of Veterinary Medicine
      during routine farm calls were included. Treatment was based on in vitro
      susceptibility testing of the bacterial isolate. Procaine penicillin G (86 cases
      due to beta-lactamase negative strains) or amoxycillin-clavulanic acid (24 cases
      due to beta-lactamase positive strains) was administered parenterally and
      intramammarily for 5 days. Efficacy of treatments was assessed 2 and 4 weeks
      later by physical examination, bacteriological culture, determination of CMT,
      somatic cell count and NAGase activity in milk. Quarters with growth of S. aureus
      in at least one post-treatment sample were classified as non-cured. As controls
      we used 41 clinical mastitis cases caused by penicillin-susceptible S. aureus
      isolates treated with procaine penicillin G parenterally for 5 days and 15 cases
      due to penicillin-resistant isolates treated with spiramycin parenterally for 5
      days from the same practice area. Bacteriological cure rate after the combination
      treatment was 75.6% for quarters infected with penicillin-susceptible S. aureus
      isolates, and 29.2% for quarters infected with penicillin-resistant isolates.
      Cure rate for quarters treated only parenterally with procaine penicillin G was
      56.1% and that for quarters treated with spiramycin 33.3%. The difference in cure
      rates between mastitis due to penicillin-susceptible and penicillin-resistant S.
      aureus was highly significant. Combined treatment was superior over systemic
      treatment only in the beta-lactamase negative group.

PMID- 14650545
TI  - A long-term study of Neospora caninum infection in a Swedish dairy herd.
AB  - A longitudinal study was performed in a Swedish dairy herd where Neospora caninum
      had been isolated from a stillborn calf. Starting in autumn 1994, blood samples
      from all female animals in the herd were collected once yearly until 1999. The
      sera were analysed for presence of IgG1 antibodies to N. caninum by the iscom
      ELISA, and by an avidity ELISA to establish the timing of infection. In addition,
      data on reproductive performance were compiled. During the study the percentage
      of seropositive female animals increased from 63% to 87%. In 1994 a large number
      of young animals tested seropositive although their dams were seronegative,
      indicating that a transmission of the parasite other than the vertical had
      recently occurred. Low avidity values supported this assumption. The annual
      abortion rate increased from a mean of 2% before the initiation of the study to
      9% in 1994-1998. During the same time, as judged by the avidity data, a large
      proportion of the animals shifted from being recently to being chronically
      infected. The source of the external infection in the herd could not be
      identified.

PMID- 14650546
TI  - Survival of Listeria monocytogenes in wilted and additive-treated grass silage.
AB  - Grass was field-dried to 3 different dry matter (DM) levels (200, 430 and 540
      g/kg) and inoculated with 10(6)-10(7) cfu/g of a Listeria monocytogenes strain
      sharing a phagovar occasionally involved in foodborne outbreaks of listeriosis.
      Formic acid (3 ml/kg) or lactic acid bacteria (8 x 10(5)/g) with cellulolytic
      enzymes were applied only to forages with low and intermediate DM levels. Forages
      were ensiled in laboratory silos (1700 ml) and were stored at 25 degrees C for 30
      or 90 days. After 90 days of storage, L. monocytogenes could not be detected in
      any silo, except one with the high dry matter grass without additive. After 30
      days of storage, between 10(2) and 10(6) cfu L. monocytogenes/g silage were
      isolated from the untreated silages. Increasing the DM content from 200 to 540
      g/kg did not reduce listeria counts possibly because of the lower production of
      fermentation acids (higher pH). In silages treated with additives, counts of L.
      monocytogenes were always lower than in silages without additive. In wet silages
      (DM 200 g/kg) both additives were effective, but in the wilted silages (DM 430
      g/kg) only the bacterial additive reduced listeria counts below detection level.
      Listeria counts were highly correlated to silage pH (r = 0.92), the concentration
      of lactic acid (r = -0.80) and the pooled amount of undissociated acids (r = 
      0.83).

PMID- 14650547
TI  - No peri- and postnatal effects on calves born after transfer of in vitro produced
      embryos vitrified by the open pulled straw (OPS) method.
AB  - The general objective of this study was to perform follow-up studies including
      selected peri- and postnatal characteristics on calves born after transfer of in
      vitro produced (IVP) embryos vitrified by the 'Open Pulled Straw' (OPS) method.
      An overall pregnancy rate of 16% after transfer of the OPS-vitrified IVP embryos
      was achieved and resulted in birth of 9 calves, with 11 AI calves serving as
      controls. There were no immediate or long-term effects on these calves with
      respect to birth weight, gestation length, perinatal mortality, growth rate,
      disease susceptibility and reproductive performance.

PMID- 14650548
TI  - No effect of a homeopathic preparation on neonatal calf diarrhoea in a randomised
      double-blind, placebo-controlled clinical trial.
AB  - A double-blind, placebo-controlled clinical trial of a homeopathic treatment of
      neonatal calf diarrhoea was performed using 44 calves in 12 dairy herds. Calves
      with spontaneously derived diarrhoea were treated with either the homeopathic
      remedy Podophyllum (D30) (n = 24) or a placebo (n = 20). No clinically or
      statistically significant difference between the 2 groups was demonstrated.
      Calves treated with Podophyllum had an average of 3.1 days of diarrhoea compared
      with 2.9 days for the placebo group. Depression, inappetence and fever were
      presented equally in the 2 groups. These results support the widely held opinion
      that scientific proof for the efficacy of veterinary homeopathy is lacking. In
      the European Union this implies a considerable risk for animal welfare, since in
      some countries priority is given to homeopathic treatments in organic farming.

PMID- 14650549
TI  - Mycoplasma hyopharyngis isolation from swine.

PMID- 14650550
TI  - Dietary intake and nutritional status of older adult homeless women: a pilot
      study.
AB  - A pilot study was conducted to identify eating patterns, food sources, and
      nutritional problems among a limited population of older homeless women located
      in a large urban area. Most of these women's food came from shelter meals, and
      their food intake was inadequate for most nutrients. The availability of fruits,
      vegetables, dairy products, and whole grains was very limited. Foods high in
      saturated fats and simple carbohydrates provided most of their caloric intake.
      Although some women were obese, most were found to have low BMI and mid-arm
      muscle mass area measurements indicating low body fat stores and potential muscle
      wasting.

PMID- 14650551
TI  - Dietary and activity profiles of selected immigrant older adults in Canada.
AB  - In Canada, the population of older adults is becoming ethnically diverse.
      However, our understanding of the health behaviors including diet and physical
      activity among this group is limited. The purpose of this study is to examine the
      dietary and physical activity profiles, and the factors that influence these
      behaviors, among older immigrants. The sample included 54 participants (mean age
      = 68 +/- 6 years) from Cambodian, Latin-American, Vietnamese and Polish groups.
      Measures included background questionnaire, nutrition screening tool, 24-hour
      dietary recall, and physical activity assessment. Results showed that 72.5% were
      at moderate to high risk for poor nutrition. Identified dietary issues were
      related to food preparation, nutrition management for diseases, and nutritional
      needs of the elderly. Although 83.3% reported to be physically active, the level
      was less than optimal, and barriers to physical activity were identified. The
      results are further discussed in light of health promotion and nutrition
      education among immigrant older adults.

PMID- 14650552
TI  - Time for assessment of nutrition services in assisted living facilities.
AB  - State regulations on the food and nutrition service components of care influence
      both care and service delivery of the elderly in assisted living facilities.
      Information on such regulations was abstracted from a survey of 50 states that
      had been carried out by the National Academy for State Health Policy. These data
      were supplemented by examining relevant state websites and by follow up phone
      calls. They were then evaluated using criteria recommended by expert groups.
      Forty-five states had some relevant food service and nutrition regulations, and
      five had no specific regulations. No state had regulations meeting all the
      criteria examined. The availability and completeness of food and nutrition
      regulations and standards in assisted living facilities may have life safety
      implications for older adults, and they deserve further evaluation.

PMID- 14650553
TI  - Tailoring nutrition education intervention programs to meet needs and interests
      of older adults.
AB  - Methods for determining appropriate content of older adult nutrition education
      intervention programs and strategies for effectively delivering nutrition
      messages to older learners are presented. Educators can determine the nutrition
      education needs and interests of their older learners by using results of food
      intake surveys and assessment screening tools, written surveys, interviews and
      group discussions. Findings of recent reports using these methods are summarized.
      Additionally, published experiences with and suggestions for tailoring education
      intervention programs for older adult audiences, including those of particular
      racial/ethnic groups, are reviewed. The need for research in this area is
      presented. This article is one of a series of literature reviews of topics
      related to nutrition education for older adults.

PMID- 14650554
TI  - Interactive learning for congregate nutrition site nutrition education: a pilot
      study.
AB  - Older adults who participate in the Older Americans Act Title III-C Elderly
      Nutrition Program often are at moderate to high nutritional risk. Although
      nutrition education is a component of the Elderly Nutrition Program, there are
      numerous barriers to promoting behavior change in older adults. Nutrition
      education programs targeted to congregate nutrition site participants must
      address their unique nutritional needs, while engaging them in activities that
      promote learning and motivate them to make positive behavior changes. This paper
      describes a pilot study of a theory-driven, five-lesson educational module
      designed to promote healthful eating behaviors among congregate nutrition site
      participants through interactive learning.

PMID- 14650555
TI  - Should dentists be included as members of the hospice care team?

PMID- 14650556
TI  - Dental status, xerostomia and the oral health-related quality of life of an
      elderly institutionalized population.
AB  - The author examined the relative effects of tooth loss and xerostomia on the oral
      health-related quality of life of an elderly, medically compromised population,
      living in a long-term care setting. Data were collected from 225 subjects (mean
      age: 83 years) via a questionnaire and review of dental charts. Oral health
      related quality of life was assessed using self-ratings, satisfaction ratings, an
      index of chewing capacity, the GOHAI, and OHIP-14. Almost all participants had
      one or more chronic medical conditions and were taking prescribed medications.
      Two-thirds of the study group was dentulous with a mean number of 16 remaining
      teeth. One-third of the participants had scores on a xerostomia index indicating
      marked oral dryness. In bivariate and multivariate analyses, xerostomia index
      scores were significantly associated with all oral health-related quality of life
      outcomes. Dental status was associated with chewing capacity only. The results
      suggest that xerostomia has an important influence on the well-being and quality
      of life of this population.

PMID- 14650557
TI  - Supervised toothbrushing and oral health education program in Kuwait for children
      and young adults with Down syndrome.
AB  - The authors report on the effectiveness of a school-based, supervised
      toothbrushing program among a group of 112 children with Down syndrome in Kuwait.
      The study involved 45 boys and 67 girls, who ranged in age from 11-22 years
      (mean, 14.8 years). The participants had moderate mental retardation and attended
      one of two special needs schools. Plaque was scored according to the Silness and
      Loe plaque index and gingivitis according to the Loe and Silness gingival index.
      Supervised toothbrushing and dental health education sessions were conducted
      twice a week. The program was evaluated at the end of three months. The mean
      plaque score decreased from 1.93 to 0.95 (p < 0.001), and the mean gingival score
      from 2.00 to 0.83 (p < 0.001). This three-month supervised toothbrushing program
      was effective in reducing plaque and gingivitis scores, but the key to long-term
      success of the program is sustaining the children's motivation to make oral
      hygiene a part of their daily life.

PMID- 14650558
TI  - Methicillin-resistant Staphylococcus aureus and infection control for restorative
      dental treatment in nursing homes.
AB  - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in nursing
      home residents now averages 20-35%. This includes both numerous asymptomatic
      mostly unidentified carriers, and the occasional patient with an active
      infection. Among the most common sites for positive MRSA colonization are the
      nares and mouth (saliva). Ohio State University (OSU) dental students perform
      routine restorative dental care onsite in local nursing homes using portable
      equipment including handpieces that can generate aerosols. Using a series of
      cultured test swabs and plates, this pilot study suggests that protection for
      both dental health care personnel and patients are provided by the following: 1.
      universal barrier precautions (for example, gloves, gowns, masks, hats, facial
      shields, glasses), 2. surface disinfectants, 3. pre-op 0.12% chlorhexidene mouth
      rinses, 4. high volume evacuation, 5. perioral skin scrubs. Additional infection
      control methods, techniques and equipment were evaluated and compared including
      rubber dam isolation, hand excavation and bond technique, high-speed air turbine
      and electric "high" speed handpiece. There was no indication of a special
      tendency or heightened ability of MRSA to aerosolize.

PMID- 14650559
TI  - Leukemic gingival infiltrate as an indicator of chemotherapeutic failure
      following monoclonal antibody therapy: a case report.
AB  - Treatment options are limited for patients with relapsed acute myelogenous
      leukemia (AML), particularly when the disease is refractory to standard cytotoxic
      chemotherapy. Targeted drug therapy offers the advantage of delivering higher
      doses of non-cross resistant chemotherapy with potentially less systemic
      toxicity. Gemtuzumab ozogamicin (Mylotarg, Wyeth-Ayerst Laboratories) is an
      immunoconjugate that consists of humanized anti-CD 33 antibody linked to the
      potent anti-tumor antibiotic calicheamicin and has been an effective therapy for
      some patients with relapsed AML. However, the overall utility of gemtuzumab
      ozogamicin is not well defined. For instance, it is not known how well this
      antibody will target extramedullary disease. This article reports gemtuzumab
      treatment of refractory AML in a 32-year-old man. At the time of recurrence, his
      bone marrow was hypoplastic and without leukemia, but the condition progressed
      resulting in marked leukemic infiltration of the oral mucosa. This case history
      raises the possibility that leukemic sanctuary sites may exist, and that
      monoclonal antibody therapy may have sub-optimal activity in non-medullary sites
      of disease.

PMID- 14650560
TI  - Management of a patient with Mobius syndrome: a case report.
AB  - Mobius syndrome is a rare congenital disorder with the primary diagnostic
      criteria of congenital facial and abducent nerve palsy. Orofacial anomalies and
      limb malformations may be associated with the disorder. Involvement of other
      cranial nerves also is common. Occasionally, the V, X, XI, and XII cranial nerves
      are involved, resulting in difficulty of chewing, swallowing, and coughing, which
      often leads to respiratory complications. Mental retardation and autism have been
      reported in some cases. An 18-year-old Hispanic male came to the General Practice
      Residency clinic at the University of Illinois at Chicago for dental treatment.
      The patient had a history of Mobius syndrome, mental retardation, and behavioral
      problems. Because of acute situational anxiety and violent behavior, we arranged
      for the patient to have general anesthesia while we provided complete oral
      rehabilitation. This article discusses the treatment of a patient, including
      special considerations taken during anesthesia and dental management. A review of
      the special challenges concerning patients with such a condition are reviewed.

PMID- 14650561
TI  - Asthma management.

PMID- 14650562
TI  - Teaching with slides, PowerPoint, and overhead projectors.

PMID- 14650564
TI  - Resourcing nursing education through collaboration.
AB  - The nursing shortage is also a nursing faculty shortage. The shortage of nurses
      can only be managed if the shortage of faculty is addressed. The profession needs
      creative and rigorous "research and development" strategies to secure sufficient
      educator resources across practice settings. Recent position statements of the
      American Association of Colleges of Nursing and the National League for Nursing
      on nursing education and the preparation of nurse educators recommend specific
      actions to meet these needs. The author calls for purposeful and creative
      collaboration between educators in academic and service settings to resource
      nursing education, now and in our future.

PMID- 14650565
TI  - A transformational journey from clinician to educator.
AB  - One nurse's desire to learn how to teach became a transformational journey from
      clinician to nurse educator. This article describes the author's transformative
      experiences with critical reflection and mentored teaching experiences. Insights
      gleaned from her journey and the educational literature supply recommendations
      for current nurse educators and implications for potential students.

PMID- 14650566
TI  - Getting off to a good start: faculty development in professional programs.
AB  - Developing and retaining faculty in professional programs presents some unique
      challenges. This article describes an approach to faculty development designed to
      meet the needs of new faculty members in nursing and other professional programs.
      The basic premise is that a reflective approach to teaching and scholarship
      serves the twin goal of promoting development and helping the faculty member
      prepare for various reviews. Recommendations for developing a philosophy of
      teaching and a scholarship plan are presented.

PMID- 14650567
TI  - Faculty development for teaching online: educational and technological issues.
AB  - The purpose of this article is to describe the process of creating a faculty
      development program for online instruction. Both educational and technological
      issues are discussed. Factors that will facilitate and barriers that will impede
      the implementation of online courses are included. Many faculty concerns
      regarding online courses relate to the issues of quality and student learning.
      Faculty development activities are directed to ensure that courses are developed
      using sound educational theory and principles. Online courses are first about
      student learning; using the technology is second. Thus, faculty development
      programs must be two-pronged, involving instructional design and technology. It
      is an ongoing process that must be focused on continual training and development.

PMID- 14650568
TI  - Realizing the power of simple meditations.

PMID- 14650569
TI  - Understanding chronic pain and the mind-body connection.
AB  - This article investigates the mind-body connection in chronic pain. A discussion
      of pain physiology is designed to identify the role of the neurological system in
      chronic pain perception. The gate control theory and the neurotransmitter theory
      of pain are explored. A description of mind-body and pain management methods, and
      an illustrative case study are provided. The information presented concerning
      mind-body connection in chronic pain perception will enable practicing nurses to
      be more fully aware of the chronic pain phenomenon, and lead to better chronic
      pain assessment, management, and evaluation.

PMID- 14650570
TI  - Patients voice issues of dress and address.
AB  - Establishing a positive patient care environment is one of the most basic
      concepts of health care professional practice. Dress and personal address are
      aspects of this environment that are influenced by culture and express mutual
      respect within the patient-provider relationship. The Patient Sensitivity
      Questionnaire was administered to determine how 76 Israeli inpatients perceived
      forms of address and dress in their health care environment. Patients preferred
      that their health care providers wear formal dress and be addressed by their
      formal titles. Respondents did not object to being addressed by their first
      names. Based on these results, it would seem that this Israeli sample preferred
      to retain the traditional provider-patient environment.

PMID- 14650571
TI  - Can acupuncture ease the symptoms of menopause?
AB  - In a randomized, 2-group clinical study, acupuncture was used for the relief of
      menopausal hot flushes, sleep disturbances, and mood changes. The experimental
      acupuncture treatment consisted of specific acupuncture body points related to
      menopausal symptoms. The comparison acupuncture treatment consisted of a
      treatment designated as a general tonic specifically designed to benefit the flow
      of Ch'i (energy). Results from the experimental acupuncture treatment group
      showed a decrease in mean monthly hot flush severity for site-specific
      acupuncture. The comparison acupuncture treatment group had no significant change
      in severity from baseline over the treatment phase. Sleep disturbances in the
      experimental acupuncture treatment group declined over the study. Mood changes in
      both the experimental acupuncture treatment group and the comparison acupuncture
      treatment group showed a significant difference between the baseline and the
      third month of the study. Acupuncture using menopausal-specific sites holds
      promise for nonhormonal relief of hot flushes and sleep disturbances.

PMID- 14650572
TI  - The silent killer: psychological issues in ovarian cancer.
AB  - Ovarian cancer represents about 4% of all cancers in women and is the fifth
      leading cause of death in the United States each year. Ovarian cancer is
      associated with uncertainty, anxiety, and depression. Many women present with
      advanced disease at diagnosis and are faced with aggressive surgical and medical
      protocols to treat them. To meet the needs of women with ovarian cancer, the
      effects of their physical problems on psychological adjustment must be
      identified. Health care professionals must closely monitor women with ovarian
      cancer to identify those who may require ongoing psychological care or
      psychiatric intervention. This article presents an overview of ovarian cancer,
      focusing on the psychological effects, and an intervention by oncology nurse
      specialists to address both the physical and emotional distress that accompanies
      ovarian cancer. The importance of screening for psychological distress is
      emphasized.

PMID- 14650573
TI  - Meditation's impact on chronic illness.
AB  - Meditation is becoming widely popular as an adjunct to conventional medical
      therapies. This article reviews the literature regarding the experience of
      chronic illness, theories about meditation, and clinical effects of this self
      care practice. Eastern theories of meditation include Buddhist psychology. The
      word Buddha means the awakened one, and Buddhist meditators have been called the
      first scientists, alluding to more than 2500 years of precise, detailed
      observation of inner experience. The knowledge that comprises Buddhist psychology
      was derived inductively from the historical figure's (Prince Siddhartha Gautama)
      diligent self-inquiry. Western theories of meditation include Jungian, Benson's
      relaxation response, and transpersonal psychology. Clinical effects of meditation
      impact a broad spectrum of physical and psychological symptoms and syndromes,
      including reduced anxiety, pain, and depression, enhanced mood and self-esteem,
      and decreased stress. Meditation has been studied in populations with
      fibromyalgia, cancer, hypertension, and psoriasis. While earlier studies were
      small and lacked experimental controls, the quality and quantity of valid
      research is growing. Meditation practice can positively influence the experience
      of chronic illness and can serve as a primary, secondary, and/or tertiary
      prevention strategy. Health professionals demonstrate commitment to holistic
      practice by asking patients about use of meditation, and can encourage this self
      care activity. Simple techniques for mindfulness can be taught in the clinical
      setting. Living mindfully with chronic illness is a fruitful area for research,
      and it can be predicted that evidence will grow to support the role of
      consciousness in the human experience of disease.

PMID- 14650574
TI  - Our heels are praying very hard all day.
AB  - In this article, prayer is represented not as a single or individual action, but
      as an entirely integrated part of nursing work. Case examples from American,
      Irish, and Australian Catholic women's religious congregations who nursed in
      hospitals in the 19th century are used to analyze the significance of prayer to
      Catholic sisters' nursing. The issue highlighted in this historical examination
      of prayer is the power of the sickroom (particularly the deathbed scene) in the
      battle for souls. Sisters' prayers functioned as invitations to religious
      experiences and means for patients to meet God. Although based on an ancient
      religion that embraced medieval notions of penance and Counter-Reformation
      evangelism through good works, sisters' practices, in the turmoil of 19th-century
      immigration and social upheaval, contributed greatly to the production of the
      modern hospital and the modern nurse.

PMID- 14650575
TI  - Putting aromatherapy in practice.

PMID- 14650576
TI  - In vitro evaluation of the dissolving effect of solvents on root canal sealers.
AB  - The purpose of this in vitro study was to evaluate two commonly used gutta-percha
      solvents for their effectiveness in dissolving several types of root canal
      sealers. Seven different sealers (AH26, AH Plus, Diaket, Roekoseal, Sankin
      Apatite Root Sealer, Sealapex, and Sultan U/P) were used in this study. After
      mixing according to the manufacturers' directions, each material was syringed
      into 30 glass capillary tubes, and a total of 210 tubes were placed in a
      humidifier at 37 degrees C for one week to allow the materials to set completely.
      Each group of 30 tubes, obturated with one type of sealer, was then randomly
      divided into three subgroups, including 10 tubes each. Chloroform was used in the
      first ten tubes from each sealer group. Halothane was used for the second group.
      In the last group, the sealer was removed with files, without using any solvent.
      The time necessary to pass a file through to the end of the tube was recorded for
      each sample in seconds. Results were analyzed using one-way analysis of variance.
      Sealapex did not set at all unless in contact with air. Roekoseal did not adhere
      to the glass capillary tubes, and was therefore easily removed from the tube in
      all samples. AH26 and AH Plus root canal sealers tightly adhered to the tube
      walls, so none of the techniques were effective in removing them from the tubes
      within 30 min. Diaket root canal sealer was easily removed using solvents (P <
      0.05). There was no advantage in using solvents to remove Sankin Apatite Root
      Sealer (P > 0.05). Solvents were found to be very effective in dissolving the
      Sultan U/P root canal sealer (P < 0.05).

PMID- 14650577
TI  - The effects of extracts from periodontopathic bacteria on human periodontal
      fibroblasts stimulated with mineralization supplements.
AB  - Bacterial effects on in vitro mineralization of human periodontal fibroblasts
      (HPF) have not yet been examined in great detail. In our study, we investigated
      the effects of soluble extracts of the periodontopathic bacteria Porphyromonas
      gingivalis, Bacteroides forsythus and, Treponema denticola on cell proliferation,
      mineralization, as well as on osteoblastic markers present in HPF cultured in
      vitro, such as alkaline phosphatase (ALP) activity and collagen content.
      Periodontal fibroblasts stimulated by B-glycerophosphate, ascorbic acid and
      dexamethasone (BAD) or by dexamethasone and ascorbic acid (DA) were compared to
      unstimulated cells. During the cultivation period, the stimulation of HPF by
      combined dexamethasone and ascorbic acid (DA) had a strong inductive effect on
      proliferation, ALP activity and collagen formation. The extracts obtained from
      the periodontal pathogens had a suppressing effect on the proliferation rate of
      HPF. The extracts from P. gingivalis, B. forsythus and T. denticola caused a
      decrease in ALP activity within 24 h of application. While extracts obtained from
      P. gingivalis and B. forsythus induced a reduction in collagen content in BAD-
      and DA-stimulated HPF cells, T. denticola extracts led to an increase in
      collagen. Our data suggest that specific periodontopathic bacteria may suppress
      tissue regeneration in vivo not only by activating host defense mechanisms but
      also directly via a suppression of growth and differentiation of HPF and a
      reduction in the extracellular collagen matrix. For the process of pocket
      formation, not even the direct influence of viable bacteria seems to be
      necessary. Additionally, long-distance effects of bacteria harboured in
      periodontal pockets or in root canals may be of importance.

PMID- 14650578
TI  - Cyclopiazonic acid discharges intracellular Ca2+ stores and stimulates Ca2+
      influx in cultured human gingival fibroblasts.
AB  - The effect of cyclopiazonic acid (CPA) on changes in the intracellular free Ca2+
      concentration ([Ca2+]i) evoked by bradykinin (BK), histamine (HIST) and
      thapsigargin (TG) was investigated in human gingival fibroblasts. CPA itself dose
      dependently stimulated [Ca2+]i responses in both the absence and presence of
      extracellular Ca2+. Pretreatment with CPA (< 5 microM) enhanced the [Ca2+]i
      responses evoked by 5 nM BK and 1 mM HIST. However, CPA-pretreatment depressed
      the [Ca2+]i response evoked by 1 microM TG in a dose-dependent manner. Moreover,
      CPA accelerated the Ca2+ influx caused by 5 nM BK and 1mM HIST, but did not alter
      that caused by 1 microM TG. These results indicate that CPA discharges
      intracellular Ca2+ stores, resulting in their depletion, and enhances Ca2+ influx
      across the plasma membrane.

PMID- 14650579
TI  - Characterization of the gene encoding 200-kDa Porphyromonas gingivalis protein
      that reacts to sera from periodontitis patients.
AB  - Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is considered to
      be one of the major etiologic agents of adult periodontitis. We previously
      succeeded in molecular cloning of a 200-kDa antigenic protein (200-k AP) from P.
      gingivalis 381 by immunoscreening using sera from severe periodontitis patients
      and designated it as pMD101. We also identified amino acid sequences of the short
      peptide from a lysyl endopeptidase digested recombinant (r), 200-k AP, and found
      that the short peptide had exactly the same amino acid sequence as the
      hemagglutinin A (hagA) of P. gingivalis, which is thought to have potential use
      in a vaccine against periodontitis. In this study, we attempted to confirm
      whether 200-k AP was a molecule identical to hagA. DNA sequences of pMD157, a
      subclone encoding the 25-kDa antigenic region of pMD101, were identical to the
      same part of the hagA gene. The r200-k AP was purified for homogeneity and
      rabbits were immunized with it. The antibody against r200-k AP previously showed
      a similar Western-blot pattern as P. gingivalis lysate by monoclonal antibodies
      against hagA by literature and reacted to r130-kDa hemagglutinin. These findings
      suggest that 200-k AP is identical to hagA and that r200-k AP may be useful as an
      immunotherapy agent against periodontitis caused by P. gingivalis infection.

PMID- 14650580
TI  - Efficacy of 'Gamadent' toothpaste on the healing of gingival tissues: a
      preliminary report.
AB  - The aim of this randomised, parallel, double-blind study, in which 28 adult
      patients diagnosed with chronic gingivitis or early stages of chronic
      periodontitis were recruited, was to evaluate the efficacy of 'Gamadent'
      toothpaste compared to a placebo toothpaste. 'Gamadent' toothpaste has all the
      basic constituents of a toothpaste with the addition of a sea cucumber extract
      (SCE) of the species Stichopus sp. 1 to improve the healing potential of tissues.
      The placebo has the same basic constituents minus the extract. Out of the 28
      patients, 14 were placed in the test group who used the 'Gamadent' toothpaste,
      and 14 patients were placed in the control group (2 control subjects defaulted
      and were excluded), who brushed using the placebo toothpaste. The longitudinal
      study was carried out over a period of 3 months with assessments made at
      baseline, 1 month, 2 months and 3 months after conventional therapy at the
      baseline visit. The clinical parameters used during the trial were Plaque Index
      (PI), Gingival Index (GI), Papilla Bleeding Index (PBI) and Probing Pocket Depth
      (PPD). A predetermined number of sites on a molar, premolar, canine and an
      incisor were examined and evaluated in each quadrant. After the baseline
      assessment, the patients had full mouth scaling and debridement as well as oral
      hygiene instructions. Patients were instructed to brush their teeth twice a day
      with the toothbrush provided (Oral-B plus, size 35) and toothpaste (test or
      control), using the Bass technique. At the 1-month assessment, there were
      significant mean reductions to baseline mean values in PI (P < 0.005) and GI (P <
      0.001) in the test group as compared to the control group. At the end of the 2
      month interval, significant reductions were observed in PI, PBI and PPD (P <
      0.001). By the end of 3 months, there were significant differences in the mean
      reduction of all the parameters i.e. PI, PBI, GI and PPD (P < 0.001), between the
      test and control sites. In conclusion, 'Gamadent' toothpaste provided noteworthy
      benefits, producing statistically significant improvement in all clinical
      parameters compared to the placebo during the healing phase after conventional
      initial therapy.

PMID- 14650581
TI  - Oral candidosis in non-Hodgkin's lymphoma: a case report.
AB  - Though oral candidosis is an opportunistic fungal infection that commonly affects
      immunocompromised patients, little is known of its occurrence as a complication
      of Non-Hodgkin's lymphoma. This paper reports a case of oral candidosis in a 20
      year-old Indonesian woman with this lymphoproliferative disease. She presented
      with acute pseudomembranous candidosis on the dorsum and lateral borders of the
      tongue, bilateral angular cheilitis and cheilocandidosis. The latter is a rare
      clinical variant of oral candidosis, and the lesions affecting the vermilion
      borders presented as an admixture of superficial erosions, ulcers and white
      plaques. Clinical findings were confirmed with oral smears and swabs that
      demonstrated the presence of hyphae, pseudohyphae and blastospores, and colonies
      identified as Candida albicans. A culture from a saline rinse was also positive
      for multiple candidal colonies. Lip and oral lesions were managed with Nystatin.
      The lesions regressed with subsequent crusting on the lips, and overall reduction
      in oral thrush. As Non-Hodgkin's lymphoma is a neoplastic disease that produces a
      chronic immunosuppressive state, management of its oral complications, including
      those due to oral candidosis, is considered a long-term indication.

PMID- 14650582
TI  - Pemphigus vulgaris and complications of systemic corticosteroid therapy: a case
      report.
AB  - Pemphigus refers to a group of diseases characterized by painful lesions caused
      by intraepidermal acantholytic structures in the skin and mucous membrane. The
      exact nature of the disease remains unknown. Pemphigus is a rare chronic
      mucocutaneous disease characterized by intra-epithelial bulla formation, due to
      autoantibodies directed against proteins of the desmosome-tonofilament complex
      between keratinocytes. The bullous lesions are painful, slow to heal and with a
      tendency to become invasive. Any part of the oral cavity may be affected, with
      the soft palate, buccal mucosa and lips being the most common sites. The high
      doses and prolonged administration of corticosteroids often required to control
      the disease result in several side effects, many of which are serious or life
      threatening. In the present case, steroid treatment was begun at 180 mg/day and
      subsequently increased to 250 mg/day and 350 mg/day. Oral lesions were treated
      locally with 0.2% chlorhexidine gluconate in addition to systemic corticosteroids
      containing an immunosuppressive. Oral lesions were observed to recur without
      healing completely. Respiratory problems occured, necessitating direct lung
      radiographs and computerised tomography. Pulmonary embolism was diagnosed and the
      patient was transferred to the vascular surgery department. Unfortunately the
      patient died due to pulmonary embolism on the seventh day. Pemphigus vulgaris
      (PV) is a chronic autoimmune mucocutaneous disease that often primarily involves
      the oral cavity. Therefore, early diagnosis of oral symptoms is crucial for the
      successful treatment of PV. Although there is no consensus regarding the initial
      steroid dosage needed to induce remission, it is suggested that high doses of
      corticosteriods may cause fatal complications.

PMID- 14650583
TI  - The location of the mental foramen in a selected Malay population.
AB  - Knowledge of the position of the mental foramen is important both when
      administering regional anesthesia and performing periapical surgery in the mental
      region of the mandible. This study determines the position of the mental foramen
      in a selected Malay population. One hundred and sixty nine panoramic radiographs
      of Malay patients retrieved from a minor oral surgery waiting list were selected
      to identify the normal range for the position of the mental foramen. The foramen
      was not included in the study if there was any mandibular tooth missing between
      the lower left and right first molars (36-46). The findings indicated the most
      common position for the mental foramen was in line with the longitudinal axis of
      the second premolar (69.2%) followed by a location between the first and second
      premolar (19.6%). The right and left foramina were bilaterally symmetrical in
      three of six recorded positions in 67.7% patients. The mental foramen was most
      often in line with the second premolar.

PMID- 14650584
TI  - Panoramic radiography as an auxiliary in detecting patients at risk for
      cerebrovascular accident (CVA): a case report.
AB  - Most cerebrovascular accidents (CVAs), commonly referred to as noncardiogenic
      strokes, occur as a result of atherosclerosis involving the common, internal and
      external carotids arteries, due to atheroma formation. Several factors influence
      atheroma formation, such as hypertension, smoking, diabetes mellitus,
      hypercholesterolemia, obesity and sedentary lifestyle among others. When
      atheromas are positioned inside the vessel lumen, they alter the flow of blood,
      causing the stroke. These atheromas, that are calcified plaques, can be observed
      in panoramic radiography.

PMID- 14650585
TI  - Video-assisted lobectomy for a lung cancer patient with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVES: This retrospective study was conducted to see whether a video
      assisted lobectomy is beneficial in lung cancer patients with chronic obstructive
      pulmonary disease regarding preservation of pulmonary function compared to
      lobectomy by standard thoracotomy. SUBJECTS AND METHODS: Between 1982 and 2002,
      67 patients who underwent lobectomy for primary lung cancer showed 55% or less of
      preoperative forced expiratory volume in one second/vital capacity. Among them,
      25 patients were enrolled in this retrospective study. The remaining 42 patients
      were excluded because of no presence of a postoperative pulmonary function test.
      Nine of 25 patients underwent a video-assisted lobectomy between 1994 and 2002
      and the remaining 16 patients who underwent a lobectomy by standard thoracotomy
      between 1982 and 1994 were employed as a historical control. Perioperative
      conditions and changes in pulmonary function were compared between two groups.
      RESULTS: A parameter of chest wall damage was minor in video-assisted lobectomy
      compared to that in lobectomy by standard thoracotomy. Changes between pre- and
      postoperative percent of vital capacity, forced expiratory volume in one second
      and maximal ventilatory volume showed significantly minor deterioration or even
      improvement in video-assisted lobectomy patients. Predicted postoperative
      pulmonary function tended to be underestimated for postoperative values in video
      assisted lobectomy patients. CONCLUSIONS: Video-assisted lobectomy seemed to be
      profitable in preservation of pulmonary function in lung cancer patients with
      chronic obstructive pulmonary disease. Prediction of postoperative pulmonary
      function should be revised due to the underestimation for postoperative values in
      video-assisted lobectomy, which could offer profitable surgical treatment for
      lung cancer patients with chronic obstructive pulmonary disease.

PMID- 14650586
TI  - Haemostatic profile of small children during and following cardiopulmonary
      bypass.
AB  - OBJECTIVE: We evaluated changes of the haemostatic system during pediatric
      cardiac surgery during and after cardiopulmonary bypass (CPB). METHOD: Twenty
      five children under 15 kg of body weight undergoing open-heart surgery were
      divided into three groups; 9 patients (Group A), no bank blood was used
      throughout the surgery; 8 patients (Group B), packed red cells were used in the
      priming of CPB circuit; 8 patients (Group C) in cyanotic condition, for whom
      surgery was performed without bank blood. CPB caused a significant decrease of
      platelet counts in all three groups, the levels of which remained similar next
      morning. RESULTS: Platelet counts decreased more significantly in Group C (59+/
      27 k/mm3) than in Group A (119+/-42 k/mm3) and B (104+/-27 k/mm3). Platelet
      function-platelet activating factor test (HemoSTATUS) did not significantly
      decrease throughout the perioperative period in Group A. HemoSTATUS value
      decreased during CPB and recovered after CPB in Group B and C. Prothrombin time
      international ratio (PT-INR) and activated partial thromboplastin time were
      significantly prolonged just after CPB and recovered until next morning in all
      three groups. PT-INR was more prolonged in Group C (2.92+/-0.62) than in Group A
      (2.08+/-0.27) and B (2.42+/-0.42). There was no significant difference in
      postoperative bleeding for the first 12 hours among the three groups. CONCLUSION:
      Although extreme hemodilution during CPB significantly impairs the coagulation
      and platelet system, these changes are usually transient and tolerable with
      minimal postoperative hemorrhage. However, a prolonged CPB and preoperative
      cyanotic condition may induce a critical decrease of platelet counts and increase
      postoperative bleeding.

PMID- 14650587
TI  - Left thoracotomy approach in reoperative off-pump coronary revascularization:
      bypass grafting from the left axillary artery or descending thoracic aorta.
AB  - OBJECTIVE: Reoperative coronary bypass grafting is at high risk. Particularly in
      redo cases where the patent graft is running near the midline of the sternum, the
      graft may be exposed to injury by a median sternotomy and subsequent dissection.
      Whereas, off-pump bypass grafting from the left axillary artery or descending
      thoracic artery by a left thoracotomy approach is safe for preventing graft
      damage. METHODS: From March 1998 to February 2002, we performed off-pump coronary
      artery bypass grafting by a left thoracotomy approach in 9 patients. The left
      axillary artery was used as the inflow vessel in 4 cases, and the descending
      thoracic aorta in 5. RESULTS: The radial artery was anastomosed proximally to the
      axillary artery in 4 cases and the descending thoracic aorta in one case. The
      saphenous vein graft was anastomosed proximally to the descending thoracic aorta
      in 4 cases. Transdiaphragmatic minimally invasive bypass grafting for the right
      coronary artery was simultaneously performed in 3 cases. Postoperative cardiac
      events were ventricular arrhythmia in 6 cases and supraventricular arrhythmia in
      3 cases. There was no damage to the patent grafts. Postoperative coronary
      angiography performed in 8 cases revealed all the grafts to be patent without
      stenosis. Cardiac symptoms were not found after the operation in any of the
      cases. CONCLUSIONS: These procedures can prevent the injury to patent grafts
      caused by a median sternotomy, and will be one of the useful strategies for
      reoperative off-pump coronary artery bypass grafting.

PMID- 14650588
TI  - Preliminary results of intermittent retrograde cerebral perfusion during proximal
      aortic arch surgery.
AB  - OBJECTIVE: Continuous retrograde cerebral perfusion during aortic arch surgery is
      associated with cerebral edema. In this report, we describe the clinical use of a
      new type of intermittent retrograde cerebral perfusion. SUBJECTS AND METHODS:
      Fourteen patients with a Stanford type A dissection were included in this study.
      With the usual method of retrograde cerebral perfusion, about 2,500 mL venous
      blood is drained from bicaval cannulae into a hard-shell reservoir, and
      oxygenated blood is perfused through the superior vena caval cannula. The flow
      rate is 300 mL/min. After about 15 min, retrograde perfusion is discontinued, and
      drainage from the bicaval cannulae is restarted. When a bloodless field is
      necessary, perfusion also is discontinued. RESULTS: Two to seven cycles of
      intermittent retrograde cerebral perfusion were administered (average, 3.1+/-0.4,
      mean+/-SD). The total retrograde perfusion time was 36.0+/-1.9 min which was
      equivalent to 74.8% of the circulatory arrest time. No patient developed edema of
      the upper body. The time to wake-up was 3 to 14 h (average, 6.5+/-1.0 h). No
      patient suffered any neurologic complications even though the time of circulatory
      arrest was greater than 60 min in four cases. Head magnetic resonance imaging or
      computed tomography was performed in 12 cases, and no evidence of hypoxic brain
      injury was detected. CONCLUSIONS: Our clinical experience using a moderate amount
      of intermittent retrograde cerebral perfusion is superior to continuous
      retrograde cerebral perfusion for protecting the brain during aortic arch
      surgery.

PMID- 14650589
TI  - Cardiac involvement of hydatid disease.
AB  - OBJECTIVES: Echinococcosis is a serious health issue occurring in some
      geographical region of the world. Cardiac involvement is rare and early diagnosis
      and prompt surgical intervention are critical. SUBJECTS AND METHODS: Six patients
      with cardiac hydatid cysts underwent surgical treatment in our institution
      between April, 1996 and March, 2002. Five of the patients were female and one was
      male. Average age was 40+/-5 years with a range of 19 to 72 years. Cysts were
      located in the right ventricular outflow tract in two patients, the left
      ventricular outflow tract in one, the right atrial in one, the right ventricular
      in one and the right atrioventricular groove in one. Five patients were operated
      on using standard cardiopulmonary bypass techniques, and one was operated on
      without cardiopulmonary bypass. RESULTS: In the perioperative and the early
      postoperative period, no cardiac problems was observed. On control
      echocardiography, a ventricular septal defect was detected in one patient in the
      late postoperative period. The ventricular septal defect was repaired using
      standard cardiopulmonary bypass and was closed with a teflon patch. Patients were
      followed up for a mean period of 3.4+/-2.5 years. No mortality or recurrence was
      observed during the follow-up period. CONCLUSIONS: When hydatid cyst is
      diagnosed, the possibility of cardiac involvement should also be investigated.
      The treatment of cardiac hydatid cyst is surgical extraction of the cyst. Results
      of surgery are generally satisfactory.

PMID- 14650590
TI  - Prediction of hematogenous recurrence in patients with esophageal carcinoma.
AB  - OBJECTIVES: Despite recent advances in diagnosis and treatment of esophageal
      carcinoma, the future risk of hematogenous recurrence is still unpredictable. To
      identify risk factors of hematogenous recurrence in esophageal carcinoma, we used
      pathological and immunohistochemical analysis to examine relationships among
      clinical outcomes, clinicopathological features, and E-cadherin expression.
      METHODS: Subjects were 102 patients with thoracic esophageal cancer who had
      undergone curative esophagectomy without preoperative treatment. We used
      univariate and multivariate logistic regression analyses to examine the
      relationship among clinical outcomes, clinicopathological features, and E
      cadherin expression. RESULTS: There was no significant relationship between E
      cadherin expression and clinicopathological features at operation. However, the
      survival rates of patients with E-cadherin-negative tumors were significantly
      lower than those of patients with E-cadherin-weak and E-cadherin-positive tumors
      (P < 0.01). Disease recurrence had occurred in 49 (48.0%), with hematogenous
      recurrence in 29 (28.4%), of the 102 patients at the time of analysis. Metastasis
      occurred in liver in 14 patients, lung in 13, bone in 6, and brain in 2.
      Comparisons of hematogenous recurrences and clinicopathological features by
      multivariate regression analyses revealed significant associations between
      hematogenous recurrences; particularly in liver and lung metastasis and negative
      E-cadherin expression. With regard to the associations between the organ with the
      recurrence and the number of positive nodes; hematogenous recurrence, equal to or
      higher than lymphatic recurrence, was more likely to have occurred in patients
      with high numbers of positive nodes. Interestingly, with regard to the sites of
      positive nodes, liver metastasis was closely correlated with lymph node
      metastasis in the mid-thoracic as opposed to the abdominal region. Further, lung
      metastasis was most likely to occur in patients with cervical lymph node
      metastasis. CONCLUSIONS: Esophageal carcinoma with negative E-cadherin expression
      tended to be associated with hematogenous recurrence, particularly with liver and
      lung metastasis. Hematogenous recurrences were significantly associated with high
      numbers and the site of positive nodes, as well as with lymphatic recurrence.

PMID- 14650591
TI  - Concomitant David's operation and total arch replacement for acute type A aortic
      dissection.
AB  - A 61-year-old man complained of chest pain and developed congestive heart failure
      due to massive acute aortic regurgitation. Computed tomographic scan demonstrated
      Stanford type A aortic dissection from the aortic root to common iliac arteries.
      David's aortic valve sparing operation and total aortic arch replacement were
      applied to the patient, because the aortic dissection was extended into two
      aortic commissures and all arch vessels, though the tear was present at the
      proximal ascending aorta. The surgery was well tolerated without any significant
      complication.

PMID- 14650592
TI  - Successful repair of supravalvular aortic stenosis with ostial stenosis of the
      left coronary artery using Brom's three patch technique.
AB  - Stenotic lesion of the left coronary artery is an unnoticed but complicating
      feature of supravalvular aortic stenosis (SAS). We present successful repair of
      SAS with left coronary ostial stenosis. A 9-year-old girl was diagnosed as
      Williams syndrome associated with SAS. She had no symptoms of angina but cardiac
      catheterization revealed severe stenosis of the left coronary artery ostium. We
      adopted Brom's three patch technique, which could enlarge the aortic root and
      ostial lesion of left coronary artery inclusively. This method is also ideal
      regarding restoration of the aortic root geometry.

PMID- 14650593
TI  - Cusp commissuroplasty for tricuspid valve endocarditis.
AB  - A 19-year-old woman with a history of drug addiction suffered from sepsis and
      heart failure. Blood culture was positive for Streptococcus viridans. An
      operation was indicated because the echocardiography showed massive vegetation on
      the anterior leaflet of the tricuspid valve and severe regurgitation even though
      the endocarditis was healed with drug therapy. At operation all of the anterior
      leaflet of the tricuspid valve was resected with the vegetation. Using the
      technique of cusp commissuroplasty, the disrupted commissure was reconstructed by
      approximating the septal and posterior cusps at the level of their normal
      closure, forming a zone of apposition by using a single stitch. Leaflet
      apposition resulted in a defect between the apposed leaflets and the tricuspid
      annulus, which was patched with autologous pericardium. The tricuspid valve was
      reconstructed to function as a unicommissural bicuspid valve. The patient was
      stable during the follow-up period of two years without any medical treatment.

PMID- 14650594
TI  - Transapical aortic cannulation using a deep hypothermic procedure through a left
      thoracotomy for acute traumatic aortic rupture.
AB  - We describe a transapical aortic cannulation procedure through a left thoracotomy
      for a case of acute traumatic aortic rupture. A 26-year-old man was involved in a
      motor vehicle accident and admitted in a state of hypovolemic shock. Chest
      computed tomography findings revealed a rupture of the proximal portion of the
      descending aorta and a massive hematoma around the aorta extending into the
      thoracic cavity. Under hypothermic circulatory arrest, he underwent an emergency
      graft replacement through a left thoracotomy. We used transapical aortic
      cannulation together with femoral cannulation, in order to avoid malperfusion of
      the brain and upper body that can occur as a result of retrograde perfusion. The
      postoperative outcome was favorable. Transapical cannulation is a useful
      alternative for hypothermic aortic operations through a left thoracotomy.

PMID- 14650595
TI  - Off-pump redo coronary artery bypass grafting from descending aorta to the
      posterolateral area through a left thoracotomy in patients with a patent internal
      thoracic artery graft.
AB  - The patients were a 73-year-old man (Case 1) and 56-year-old man (Case 2) who
      developed angina pectoris and heart failure. Case 2 showed chronic renal failure
      on hemodialysis. These patients showed posterolateral myocardial ischemia with a
      patent internal thoracic artery graft to the left anterior descending artery.
      Left ventricle ejection fraction was 29% and 33%, respectively. Catheter
      intervention was unsuccessful, so we performed revascularization from the
      descending aorta to coronary arteries with saphenous vein grafts via a left
      thoracotomy using an off-pump technique. In case 2, proximal anastomosis was
      constructed with the Symmetric aortic connector. This procedure appeared to be a
      very safe and useful method as an option for redo coronary artery bypass grafting
      in the posterolateral area in patients with patent old grafts and poor left
      ventricular function.

PMID- 14650596
TI  - Video-assisted S6b-subsegmental resection after computed tomography guided
      localization of pulmonary nodules.
AB  - A 38-year-old man, who had undergone surgery for gastric cancer one year
      previously, was found to have two pulmonary nodules (PNs: 10 mm in diameter) on
      chest radiography. Computed tomography (CT) revealed one of these nodules to be
      located near the B6b in the right lung hilus, while the other was located in the
      superficial region of the left lower lobe. Video-assisted thoracic surgery (VATS)
      was performed, for both diagnostic and therapeutic purposes. In this procedure,
      after preoperative CT-guided marking, simultaneous subsegmental resection of the
      right S6b and VATS wedge resection of the left lower lobe were performed
      successfully with adequate surgical margin. Histological diagnosis was compatible
      with metastatic pulmonary tumor from a gastric carcinoma primary. This case
      demonstrates that preoperative CT-guided localization can facilitate safe VATS
      subsegmental resection of a small deep pulmonary nodule.

PMID- 14650597
TI  - Surgical repair for tracheo-innominate artery fistula with a muscle flap.
AB  - A 70-year-old woman was quickly diagnosed as having tracheo-innominate artery
      fistula by three-dimensional computed tomography. Immediate surgical exploration
      was performed to control the bleeding using a temporary shunt. After the damaged
      artery was excised, vascular reconstruction was performed to preserve the
      connection between the proximal and distal ends of the innominate artery with the
      interposition of a saphenous vein graft. A pedicled sternocleidomastoid muscle
      flap was successfully used for the tracheal reconstruction.

PMID- 14650598
TI  - Atrophic degeneration and loss of myocytes of residual left ventricular
      myocardium after Dor operation for ischemic cardiomyopathy associated with left
      ventricular remodeling.
AB  - A 32-year-old male with familial hypercholesterolemia suffered from severe left
      ventricular dysfunction caused by left ventricular remodeling after myocardial
      infarction (ischemic cardiomyopathy), and endoventricular circular patch plasty
      (Dor operation) was performed. The patient's postoperative recovery was
      favorable. Postoperative left ventricular function was significantly improved and
      the patient was discharged from our hospital. However, about 5 months later, the
      patient developed congestive heart failure, which progressed rapidly and
      irreversibly, with death at postoperative month 6. At autopsy, atrophic
      degeneration and loss of myocytes of the residual left ventricular myocardium
      were suggested to be the cause of irreversible heart failure. The postoperative
      balance between function of the residual myocardium and reduced left ventricular
      volume should be considered in cases of Dor operation for ischemic cardiomyopathy
      with left ventricular remodeling.

PMID- 14650599
TI  - Spontaneous thymic cyst hemorrhage causing hemothorax.
AB  - The case describes a 56-year-old man who had thymic cyst hemorrhage, followed by
      right hemothorax. There was a high possibility that his accompanying disease, an
      alteration in hemostasis due to alcoholic liver cirrhosis and hypertension, would
      induce thymic cyst hemorrhage. Thymic cyst hemorrhage should be included in
      possible causes of the sudden onset of mediastinal or intrathoracic hemorrhage,
      in addition to the rupture of aortic aneurysm or malignant mediastinal tumor.

PMID- 14650600
TI  - Methods for generating second dimension retention index data in comprehensive two
      dimensional gas chromatography.
AB  - Two methods of generating transportable second dimension retention data are
      outlined for comprehensive two-dimensional gas chromatography (GC x GC). They are
      both refinements of a previously outlined procedure, which adapted 'isovolatile'
      curves to retention prediction maps developed in our laboratory, extended to a
      more polar homologous series, the linear primary alcohols. The earlier work
      investigated maps based on alkanes and methyl ketones and methyl esters; here the
      method of data collection to generate the retention map has also changed,
      extending the retention base range. The resulting retention map permits a
      retention basis to be used for GC x GC data, however, a more polar retention set
      than alkanes is required. The calculation of 'retention indices' is aided by the
      generation of 'fractional reference compound' curves, by either direct
      manipulation of data local to the solute, or generation of a discrete curve
      coincident with the retention co-ordinates of the target compound.

PMID- 14650601
TI  - Quantitative analysis of target components by comprehensive two-dimensional gas
      chromatography.
AB  - Quantitative analysis using comprehensive two-dimensional (2D) gas chromatography
      (GC) is still rarely reported. This is largely due to a lack of suitable
      software. The objective of the present study is to generate quantitative results
      from a large GC x GC data set, consisting of 32 chromatograms. In this data set,
      six target components need to be quantified. We compare the results of
      conventional integration with those obtained using so-called "multiway analysis
      methods". With regard to accuracy and precision, integration performs slightly
      better than Parallel Factor (PARAFAC) analysis. In terms of speed and
      possibilities for automation, multiway methods in general are far superior to
      traditional integration.

PMID- 14650602
TI  - Chemometric approach for the resolution and quantification of unresolved peaks in
      gas chromatography--selected-ion mass spectrometry data.
AB  - A semiautomated and integrated chemometric approach is presented for the
      resolution and quantification of unresolved target-analyte signals in gas
      chromatography-selected-ion monitoring (GC-SIM) data collected using scanning
      mass spectrometers. The chemometric approach utilizes an unskewing algorithm and
      two multivariate chemometric methods known as rank alignment and the generalized
      rank annihilation method (GRAM). The unskewing algorithm corrects the retention
      time differences within a single GC-SIM data matrix caused by using a scanning
      mass spectrometer. Rank alignment objectively corrects the run-to-run retention
      time difference between a sample GC-SIM data matrix and a standard addition GC
      SIM data matrix. GRAM analysis uses the sample and standard addition data
      matrices to mathematically resolve and quantify the target-analyte signal(s). The
      resolution and quantification of severely unresolved target-analyte signals are
      demonstrated using GC-SIM data obtained from conventional heart-cut two
      dimensional gas chromatography with mass spectrometric detection. In addition,
      the GC-SIM data is used to demonstrate the result of chemometric analysis when
      the absence of a target-analyte signal is obscured by interference. Chemometric
      analysis is shown to unambiguously detect an analyte based on its resolved mass
      chromatograms in situations where the traditional approach of measuring peak
      height fails to positively detect it. The predicted analyte concentrations are
      within 8% of the reference concentrations.

PMID- 14650603
TI  - Comprehensive two-dimensional gas chromatography using liquid nitrogen
      modulation: set-up and applications.
AB  - An improved modulation system for comprehensive two-dimensional gas
      chromatography (GC x GC) is presented. It is based on two-jet modulation with
      liquid nitrogen as cryogen. A valve system was designed to include subsequent re
      heating of cooled capillary segments after modulation. It is demonstrated that
      even volatile components, such as propane or butane, are easily modulated with
      this system. Thus, the temperature range for GC x GC operation compared to
      diaphragm valve or liquid CO2 modulation is extended. The system allows highly
      efficient analysis of volatile and non-volatile components. Applications include
      separations of alkenes and gasoline samples. Also sulfur-containing hydrocarbon
      samples were compared via GC x GC and differences among samples of different
      producers were observed. Finally, headspace GC x GC investigations of volatiles
      found in polymer latex-coated papers round out the increasing portfolio of
      valuable applications.

PMID- 14650604
TI  - New liquid nitrogen cryogenic modulator for comprehensive two-dimensional gas
      chromatography.
AB  - A new liquid nitrogen (LN2) jet-based thermal modulator for performing
      comprehensive two-dimensional (2D) gas chromatographic (GC x GC) separations has
      been designed and constructed. Temperature measurements of the trapping zone, a
      segment of uncoated fused silica capillary, show that it can be cooled to -196
      degrees C in about 300 ms. A film of liquid nitrogen develops on the outside of
      the trapping capillary even when the oven temperature is in excess of 200 degrees
      C. Compounds as volatile as propane can be trapped by the modulator and held for
      periods of at least 1 min without breakthrough. The peak widths for n-alkanes are
      on the order of 80 ms at half height after passing through an 80cm second
      dimension column. Repeated analysis of gasoline demonstrated excellent run-to-run
      reproducibility of the system.

PMID- 14650605
TI  - Evaluation of modulators and electron-capture detectors for comprehensive two
      dimensional GC of halogenated organic compounds.
AB  - Different cryogenic and a heated GC x GC modulator(s) were evaluated and compared
      for the analysis of high-boiling halogenated compounds. The cryogenic modulators
      investigated were: (i) the longitudinally modulated cryogenic system; (ii) the
      liquid-nitrogen-cooled jet modulator (KT2001); (iii) a dual-jet CO2 modulator
      (made in-house); (iv) a semi-rotating cryogenic modulator (made in-house) and (v)
      a CO2 loop modulator (KT2003); the heated modulator was the slotted heater system
      (sweeper). Each modulator was optimised with respect to analyte peak widths at
      half height in the second-dimension. n-Alkanes, chlorinated alkanes,
      polychlorinated biphenyls (PCBs) and fluorinated polycyclic aromatic hydrocarbons
      (F-PAHs) were used as test analytes. The flow rate of the coolant was found to be
      an important parameter, i.e. the flow rate of the gaseous nitrogen in the KT2001,
      and of the liquid CO2 in the other cryogenic modulators. For the slotted heater
      the stroke velocity and pause time were important parameters. This modulator had
      a limited application range in terms of temperature due to a necessary 100
      degrees C difference between sweeper and oven temperature. All cryogenic
      modulators were found to be suitable for the GC x GC analysis of high-boiling
      compounds, but the CO2 modulators are to be preferred to the KT2001 due to a
      wider application range and slightly narrower peaks. As regards the performance
      of three commercially available electron-capture detectors (ECDs), the aim was to
      obtain narrow peak widths in GC x GC, i.e. to avoid band broadening caused by the
      cell volume. The most important parameters were the flow rate of the make-up gas
      and the detector temperature which both should be as high as possible. Comparison
      of analyte peak widths obtained with ECD mode and flame ionisation detection
      (FID) showed that all ECDs exhibited band broadening compared to the FID. The
      narrowest peaks were obtained with the Agilent micro-ECD, which has a cell volume
      of only 150 microl.

PMID- 14650606
TI  - Valve-based comprehensive two-dimensional gas chromatography with time-of-flight
      mass spectrometric detection: instrumentation and figures-of-merit.
AB  - A valve-based comprehensive two-dimensional gas chromatograph coupled to a time
      of-flight mass spectrometer (GC x GC/TOFMS) is demonstrated. The performance
      characteristics of the instrument were evaluated using a complex sample
      containing a mixture of fuel components, natural products, and organo-phosphorous
      compounds. The valve-based GC x GC, designed to function with an extended
      temperature of operation range, is shown to have high chromatographic resolution,
      high separation efficiency and low detection limits. Typical peak widths at base
      are nominally from 100 to 300 ms on column 2 and nominally 10 s on column 1. The
      injected mass and injected concentration limit of detection (LOD), defined as 3
      standard deviations above the mean baseline noise, for three organo-phosphorous
      compounds (triethylphosphorothioate (TEPT), dimethyl methyl phosphonate (DMMP)
      and dimethyl phosphite (DMP)) in a complex environmental sample were from 6 to 38
      pg, and 3 to 17 ng/ml, respectively. The temperature program for the
      environmental sample ranged from 40 to 230 degrees C, a temperature range capable
      of analyzing semi-volatile compounds. A new compact, stand-alone, valve-pulse
      generator device has been implemented and is also reported. The valve-based GC x
      GC instrument, therefore, offers a simple, rugged and less expensive alternative
      to thermally modulated instruments.

PMID- 14650607
TI  - Comprehensive two-dimensional gas chromatography with atomic emission detection
      and correlation with mass spectrometric detection: principles and application in
      petrochemical analysis.
AB  - Comprehensive gas chromatography (GC x GC) has been combined with atomic emission
      detection (AED) to enable element-selective detection. Under optimised
      experimental conditions, the requirement of minimum five data points across a
      peak can be obtained even for analytes eluting early from the second-dimension
      column. Simple manipulation of the results allows the combined presentation of up
      to four sets of elemental data in one two-dimensional plot. GC x GC with AED and
      mass spectrometric (MS) detection in petrochemical analysis for fingerprinting as
      well as the identification of N- and S-containing unknowns is presented as an
      application.

PMID- 14650608
TI  - Determination of sulfur-containing compounds in diesel oils by comprehensive two
      dimensional gas chromatography with a sulfur chemiluminescence detector.
AB  - This article reports an analytical method for separating, identifying and
      quantitating sulfur-containing compounds and their groups in diesel oils (170-400
      degrees C) using comprehensive two-dimensional gas chromatography coupled with a
      sulfur chemiluminescence detector. The identification of target compounds and
      their groups was based on standard substances, the group separation feature and
      tile-effect of comprehensive two-dimensional gas chromatography. The quantitative
      analysis on major sulfur compounds and total sulfur was carried out based on the
      linear response of sulfur chemiluminescence detector and the internal standards
      method. The results of total sulfur determination in the samples were compared
      with those from ASTM D 4294 standard method, the R.S.D. percentage were <6.02%,
      correctness of this method can meet the industrial requirement. To the end, the
      method developed was used to investigate the sulfur-containing compounds in
      different diesel oils, the result shows that the distribution of sulfur
      containing compounds in diesel oils from different process units are apparently
      different. The sulfur compounds in fluid catalytic cracking (FCC), residuum fluid
      catalytic cracking (RFCC) diesel oils mainly exist in the form of alkyl
      substituted dibenzothiophenes that add up to about 40-50% of the total sulfur,
      while this number is only 6-8 and 20-28% in visbreaking (VB) and delayed-coking
      (DC) diesel oils, respectively.

PMID- 14650609
TI  - Comprehensive two-dimensional gas chromatography of the 209 polychlorinated
      biphenyls.
AB  - Comprehensive two-dimensional gas chromatography (GC x GC) of the 209
      polychlorinated biphenyls (CBs) was carried out using a longitudinally modulated
      cryogenic system (LMCS) and liquid carbon dioxide as cryogen. The effluent from a
      non-polar column was modulated and further separated on either a polar or a shape
      selective second-dimension column. Five GC x GC column combinations were
      evaluated, with DB-XLB as the first column in each case. DB-XLB separates more
      congeners than any other GC column currently available. When combined with a
      biscyanopropyl siloxane (SP-2340 or BPX70) or smectic liquid crystal (LC-50)
      second-dimension column in a GC x GC system many additional CBs can be separated.
      In total, 176 and 181 of the 209 congeners were separated (Rs = 0.5) on the
      column combinations DB-XLB/SP-2340 and DB-XLB/LC-50, respectively. Of the 136 CBs
      present in any Aroclor mixture at concentrations greater than 0.05% (w/w), 126
      were resolved using either of these two column combinations. The seven frequently
      measured CBs 28, 52, 101, 118, 138, 153, 180, and the WHO-PCBs 77, 81, 105, 114,
      118, 123, 126, 156. 157, 167, 169 and 189 were all separated from Aroclor CBs on
      the DB-XLB/LC-50 column set, whereas CBs 118 and 131 coeluted on the DB-XLB/SP
      2340 column set. In addition, three technical CB formulations (Aroclors 1232,
      1248 and 1260) and a seal blubber sample (Halichoerus grypus) from the Baltic Sea
      were analyzed. Similar peak patterns were found for Aroclor 1260 and the CBs in
      the seal blubber, facilitating use of this technical CB formulation to identify
      the CBs in the blubber by GC x GC. Individual CBs in environmental samples, such
      as seal blubber, may be identified semi-automatically by matching the samples GC
      x GC profiles to a template generated using a standard containing all 209 CBs.
      Using such a template, 64 CBs were identified in the grey seal blubber sample.

PMID- 14650610
TI  - Determination of atropisomeric and planar polychlorinated biphenyls, their
      enantiomeric fractions and tissue distribution in grey seals using comprehensive
      2D gas chromatography.
AB  - High prevalence of uterine occlusions and sterility is found among Baltic ringed
      and grey seal. Polychlorinated biphenyls (CBs) are suspected to be the main
      cause. The CB concentrations are higher in affected than in healthy animals, but
      the natural variation is considerable. Thus, it might be possible to assess the
      health status of seals by CB analysis. The ratios of chiral compounds
      (enantiomeric fractions (EFs)) such as atropisomeric CBs are of
      particularinterest, since these may reflect differences in metabolic rates. An
      analytical procedure was developed and used to determine the levels of
      atropisomeric CBs, planar-CBs (WHO-PCBs) and total CBs in seals of different
      health status. Comprehensive 2D gas chromatography (GC x GC) was used to separate
      the target analytes from other CBs and interferences and a micro electron-capture
      detector (microECD) was used for detection. EFs of the atropisomeric CBs were
      difficult to determine as the levels were low and the interferences many. Two
      column combinations bad to be used to avoid biased results-both had a chiral
      column as first-dimension column. The second-dimension column was coated with
      either a high-polarity cyanopropyl or a liquid crystal phase. EFs were determined
      for five atropisomeric CBs, i.e. CBs 91,95, 132, 149 and 174. The results were
      verified by GC x GC-time-of-flight mass spectrometry (TOF-MS). Some atropisomeric
      CBs had EFs that deviated strongly from the racemic-mixture value. The deviations
      were larger in liver than blubber, which indicates enantioselective metabolism.
      However, there was no selective passage of the studied atropisomeric CBs across
      placenta and no selective blood-brain barrier. Similarly, no correlation between
      EFs and health status was observed, although there was a correlation between the
      total CB levels and health status.

PMID- 14650611
TI  - Qualitative evaluation of thermal desorption-programmable temperature
      vaporization-comprehensive two-dimensional gas chromatography-time-of-flight mass
      spectrometry for the analysis of selected halogenated contaminants.
AB  - The separation of 38 toxic and predominant polychlorinated biphenyl (PCB)
      congeners, 11 persistent halogenated pesticides, 1 brominated biphenyl (BB), and
      8 polybrominated diphenyl ethers (PBDEs) has been optimized using comprehensive
      two-dimensional gas chromatography coupled to time-of-flight mass spectrometry
      (GC x GC-TOFMS). A thermal desorption-programmable temperature vaporization (TD
      PTV) step was used for the injection. Different column sets were investigated,
      and a 100% dimethylpolysiloxane (15 m x 0.25 mm i.d. x 0.25 microm film
      thickness) narrowbore capillary column coupled to a high temperature (8% phenyl)
      polycarborane-siloxane (2 m x 0.10 mm i.d. x 0.10 microm film thickness)
      microbore column set was selected. Of the 58 compounds investigated, only one
      pair of PCBs was not resolved. All other analytes were either baseline separated
      into the chromatographic plane or were virtually separated using the
      deconvolution capability of the TOFMS.

PMID- 14650612
TI  - Comprehensive two-dimensional gas chromatography with time-of-flight mass
      spectrometric detection for the trace analysis of flavour compounds in food.
AB  - The practicability and potential of comprehensive two-dimensional gas
      chromatography coupled to time-of-flight mass spectrometry (GC x GC-TOF-MS) for
      the analysis of complex flavour mixtures in food were studied. With the
      determination of key flavour targets in dairy samples as an example, it was
      demonstrated that GC x GC dramatically improves the separation. As a consequence,
      identification and, more importantly, quantification down to the ng/g level can
      be performed more reliably: background interferences largely disappear. Next to
      the peak table generated from the GC-TOF-MS software after data processing, the
      additional use of well-ordered patterns in the 2D-plane and information from
      second-dimension retention times can substantially help the identification of
      unknowns. The technique was successfully used for an evaluation of extraction
      techniques and the characterisation of different types of samples.

PMID- 14650613
TI  - Evaluation of two-dimensional gas chromatography-time-of-flight mass spectrometry
      for the determination of multiple pesticide residues in fruit.
AB  - In recent years, comprehensive two-dimensional gas chromatography (GC x GC) has
      attained increasing attention for its outstanding separation potential and
      capability to solve demanding analytical tasks. Trace level analysis of
      pesticides residues in complex food matrices represents such a demanding task.
      For some commodities, such as baby food, the requirements on method detection
      limits are very strict and the unambiguous confirmation of the pesticide presence
      based on mass spectrometric detection is required. In this work, GC x GC coupled
      to time-of-flight mass spectrometry (TOF MS) has been evaluated for the
      determination of pesticides residues in fruit samples. Twenty modern pesticides
      with a broad range of physico-chemical properties were analysed in apple and
      peach samples. It has been demonstrated that the application of comprehensive two
      dimensional gas chromatography brings distinct advantages such as enhanced
      separation of target pesticides from matrix co-extracts as well as their improved
      detectability. The limits of detection of the pesticides comprised in the study
      (determined at S/N = 5) ranged from 0.2 to 30 pg, injected with the exception of
      the last eluted deltamethrin, for which 100 pg could be detected. When compared
      to one-dimentional GC-TOF MS analysis under essentially the same conditions the
      detectability enhancement was 1.5-50-fold. Full mass spectral information by time
      of-flight mass spectrometry and the deconvolution capability of the dedicated
      software allowed for reliable identification of most pesticides at levels below
      0.01 mg/kg (< 10 pg injected) in fruit. Performance characteristics of the GC x
      GC-TOF MS method, such as linearity of calibration curves, repeatability of
      (summed) peak areas, as well as repeatability of first and second dimension
      retention times, were shown to fully satisfy the requirements for trace level
      analysis of the pesticide residues in food.

PMID- 14650614
TI  - Detailed analysis and group-type separation of natural fats and oils using
      comprehensive two-dimensional gas chromatography.
AB  - Comprehensive gas chromatography (GC x GC) is an adequate methodology for the
      separation and identification of very complex samples. It is based on the
      coupling of two capillary columns that each give a different but substantial
      contribution to the unprecedented resolving power of this technique. The 2D space
      chromatograms that derive from GC x GC analysis have great potential for
      identification. This is due to the fact that the contour plot positions,
      pinpointed by two retention time coordinates, give characteristic patterns for
      specific families of compounds that can be mathematically translated. This
      investigation concerned the application of this principle to fatty acid methyl
      esters that were grouped on an equal double bond number basis. The ester samples
      were derived from various lipids and all underwent bidimensional analysis on two
      sets of columns. Peak attribution was supported by mass spectra, linear retention
      indices and information reported in the literature.

PMID- 14650615
TI  - Application of comprehensive two-dimensional gas chromatography to the
      quantification of overlapping faecal sterols.
AB  - Standard solutions containing a mixture of seven sterols and 5alpha-cholestane as
      internal standard, and sample mixtures that comprised varying ratios of sterol
      and stanols from green lip mussel tissue and dried cow faeces were analysed by
      using comprehensive two-dimensional gas chromatography (GC x GC). Quantitative
      results were compared with single-column GC analysis. The latter samples included
      sterols of interest, but which cannot be readily obtained elsewhere. It may also
      mimic potential environmental samples where dairy production and aquaculture
      (oyster, mussel cultivation) share the same catchment; environmental sterol
      signatures may exhibit characteristics of both sample types comprising this
      mixture. Whereas single-column GC-flame ionisation detection was unable to
      reliably quantitate target sterols, the GC x GC experiment permitted small
      amounts of sterols and stanols to be detected and separated. Likewise GC-MS
      analysis was unable to detect some of the minor sterols which coeluted on a
      single column. The GC x GC mode allows complete separation of several important
      sterols and stanols, such as 24-ethylcoprostanol, campesterol and 24
      methylenecholesterol, demonstrating the enhanced resolving power of the GC x GC
      system. Separation of 24-ethyl-epi-coprostanol from several algal-derived
      interfering components was achieved, leading to higher degree of confidence in
      the quantitative analysis of faecal sterols. The effects of a number of operating
      variables--column length, carrier flow-rate and elution temperature--on component
      resolution and presentation of data in the two-column analysis are described.

PMID- 14650616
TI  - Comprehensive two-dimensional gas chromatography using large sample volume
      injection for the determination of polynuclear aromatic hydrocarbons in complex
      matrices.
AB  - The sensitivity of a gas chromatography (GC) analytical method can be
      substantially enhanced by injecting large sample volumes. The novel Large Volume
      Splitless injection technique was used in combination with comprehensive two
      dimensional GC (GC x GC), taking advantage of the improved detectability and the
      very high separation capability. An experimental version of Thermo Electron TRACE
      GC Ultra using a cryogenic dual jet modulator was utilized with a fast flame
      ionization detector (FID) for the analysis of low ppbs level of PAHs compounds in
      very complex matrices. Experimental data (relative standard deviation of 1%
      evaluated on a standard mixture) demonstrate the reliability of the whole system.
      A dedicated data system is presented for acquiring and managing GC x GC data:
      three-dimensional and color plot visualization, peaks integration, identification
      and quantitation are functions available with the software.

PMID- 14650617
TI  - Pressurised liquid extraction--comprehensive two-dimensional gas chromatography
      for fast-screening of polycyclic aromatic hydrocarbons in soil.
AB  - Pressurised liquid extraction (PLE) was applied to the extraction of polycyclic
      aromatic hydrocarbons (PAHs) from contaminated soils from Husarviken in
      Stockholm, Sweden. The extraction step was followed by conventional gas
      chromatography (GC), comprehensive two-dimensional gas chromatography (GC x GC)
      (both with flame ionisation detection) and gas chromatography-quadrupole mass
      spectrometry (GC-MS) analysis. Qualitative and quantitative aspects of the
      results are considered. Qualitatively, results from all chromatographic analyses
      are in good agreement, and PLE provides a reliable extraction technique with all
      PAHs extracted in one extraction step; no carry over was observed. With respect
      to PAH quantification, some variability in results was noted, with better
      agreement in PAH concentrations for GC and GC x GC measurement, as compared to GC
      MS. GC analysis compares favourably with GC x GC apart from the few exceptions
      where peaks are not fully resolved from other co-extracted analytes, which
      compromises GC-FID measurement. For example, acenaphthene shows a much higher
      concentration when measured by GC-FID, demonstrating the superior separating
      powers of GC x GC; the latter is the preferred technique if precise and accurate
      quantification of analytes are required. GC-MS results compare reasonably with GC
      x GC for low-molecular mass PAHs but not for high-molecular mass PAHs; results
      for GC-MS are consistently higher than those for GC x GC for high-molecular mass
      PAHs. Since PLE-GC x GC is proposed as a broad screening tool, the demand for
      precise quantification may be relaxed in the present situation. GC x GC has the
      added advantage of providing chemical structural information within the two
      dimensional contour presentation. Reproducibilities for GC x GC results (peak
      area) and 2tR were acceptable with relative standard deviations (R.S.D.) of 8 and
      1%, respectively (at the mg/kg level), and good repeatability within samples was
      achieved.

PMID- 14650618
TI  - Search criteria and rules for comprehensive two-dimensional gas chromatography
      time-of-flight mass spectrometry analysis of airborne particulate matter.
AB  - Direct thermal desorption-gas chromatography-time-of-flight mass spectrometry
      (DTD-GC-TOFMS) and comprehensive two-dimensional (2D) gas chromatography-time-of
      flight mass spectrometry (GC x GC-TOFMS) was applied for characterisation of semi
      volatile organic compounds (SVOC) in fine particulate matter (PM), with a
      diameter of up to 2.5 microm (PM2.5), from ambient air in Augsburg, Germany. DTD
      GC-TOFMS measurements on the SVOC in PM2.5 are done on a daily basis (time series
      over several years). The data will be used in an epidemiological study
      questioning the influence of SVOC in PM2.5 on ambient aerosol related health
      effects. The outcome of the first measurements periods is that the organic
      inventory in the ambient aerosol can undergo drastic fluctuations, e.g. due to
      meteorological influences or specific emission sources. This includes also the
      large fraction of chromatographically not resolved peaks (unresolved carbonaceous
      matter (UCM)). The UCM fraction contains about 70% of the SVOC mass in PM2.5. GC
      x GC-TOFMS is a suited technique to study the nature of the yet unidentified
      compounds forming the UCM. The considerably increased chromatographic resolution
      in GC x GC allows separation of many UCM compounds while the TOFMS supplies mass
      spectral data of all separated compounds. However, the data sets are getting
      enormously complex. In a typical PM2.5 sample from Augsburg more than 15,000
      peaks can be detected. Thus, it is important to classify the observed GC x GC
      peaks by rational means. A classification procedure based on GC x GC retention
      times and the fragmentation patterns is suggested. With a preliminary
      classification procedure it is already possible to group compounds with some
      certainty into substance classes. After some further development, this approach
      can be used for classifying GC x GC data, e.g. for environmental and
      epidemiological studies.

PMID- 14650619
TI  - Comprehensive two-dimensional gas chromatography in the analysis of urban
      aerosols.
AB  - Comprehensive two-dimensional gas chromatography utilising a semi-rotating
      cryogenic modulator was applied to the analysis of urban aerosols. Samples were
      collected onto glass fibre filters using a high-volume sampler in Helsinki,
      Finland. Sample preparation included extraction into n-hexane-acetone mixture and
      clean-up on silver-impregnated silica column. Analyses were performed with GC x
      GC-FID and GC x GC-QMS equipment. Linearity of the method was good with R2 values
      greater than 0.994 for all analytes. Polycyclic aromatic hydrocarbons (PAHs) and
      oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) were identified and
      quantified in urban particulates. PAH and oxy-PAH concentrations ranged from 0.5
      to 5.5 ng/m3.

PMID- 14650620
TI  - Standardized test mixture for the characterization of comprehensive two
      dimensional gas chromatography columns: the Phillips mix.
AB  - A novel column characterization test mixture is developed for use in
      comprehensive two-dimensional gas chromatography (GC x GC). This mixture has been
      named the "Phillips mix" in honor of the late professor John B. Phillips, the
      father of GC x GC. The mixture comprises a series of homologous compounds from
      structural groups that cover a volatility and polarity range that is similar to
      the Grob mix, and includes saturated hydrocarbons (alkanes), unsaturated
      hydrocarbons (alkenes and alkynes), carbonyls (ketones and aldehydes), primary
      alcohols, fatty acid methyl esters, alkyl ethers, carboxylic acids, aromatics, as
      well as other unique functional groups (such as amines, etc.). Similarly to the
      Grob mix in conventional one-dimensional GC, the Phillips mix can be used as a
      standardized test for performance characterization of GC x GC column sets. Unlike
      the Grob mix, however, the Phillips mix's most important use is as a practical
      guideline for column users. This paper addresses some qualitative aspects of the
      use of the Phillips mix through an investigation of the chromatographic
      fingerprints of two different GC x GC column combinations.

PMID- 14650621
TI  - Retention time reproducibility in comprehensive two-dimensional gas
      chromatography using cryogenic modulation. II. An interlaboratory study.
AB  - An interlaboratory survey was conducted to determine the reproducibility of
      retention times in both the first (1D) and second dimension (2D) axes of the two
      dimensional separation space, using the longitudinal cryogenic modulation
      comprehensive two-dimensional gas chromatographic approach. Intralaboratory
      reproducibility has been demonstrated in part 1 of this investigation [J.
      Chromatogr. A 968 (2002) 161]. Confidence in absolute retention times (hence
      component positions) in the two-dimensional separation space is critical to
      component identification. Comparing data from four independent laboratories, five
      independent gas chromatographs, five independent LMCS units, and numerous
      operators has determined that the LMCS cryogenic modulation approach provides
      reliable comprehensive two-dimensional GC results.

PMID- 14650622
TI  - Trace elements, anxiety and immune parameters in patients affected by cancer.
AB  - The aim of this case-control study was to investigate the relationship between
      trace elements, immune parameters, and human cancer, taking into account some
      personality traits, such as anxiety, implicated in the modulation of both immune
      responses and pathology. Thirty patients affected by the most frequent cancer
      types were recruited at the onset of disease together with 30 healthy controls.
      Se, Zn and Cu were measured in plasma together with glutathione peroxidase (GSH
      Px) activity, and lipid peroxidation (thiobarbituric acid-reactive substances-
      TBARS). Furthermore, Zn and GSH-Px activity were measured in red blood cells. A
      complete blood profile with the main lymphocytes subsets was obtained and the
      State-Trait Anxiety Inventory was applied to evaluate anxiety. The only
      differences found between trace element levels in cases and controls were
      significantly higher erythrocyte Zn in cancer patients and higher plasma Cu
      levels in male patients. In addition, subjects affected by cancer exhibited a
      significant reduction in TBARS levels, were more anxious, had lower total B cells
      percentage and T helper/T suppressor ratio, and had a higher percentage of
      natural killer cells. Interestingly, in patients only, GSH-Px in plasma was
      positively related to trait anxiety scores (p < 0.02) and Cu to state anxiety
      scores (p < 0.05). In conclusion, we could not confirm the existence of trace
      element deficiency in relation to cancer and no links between trace element
      levels and lymphocyte subsets were documented. However, interesting associations
      between state anxiety and Cu, and between trait anxiety and GSH-Px were observed
      thus deserving further investigations.

PMID- 14650623
TI  - In vitro effects of nickel-sulphate on immune functions of normal and nickel
      allergic subjects: a regulatory role for zinc.
AB  - Nickel hypersensitivity represents a very common human disease state, mainly
      occurring in females, defined as allergic contact dermatitis. Ni is a transition
      metal whose activity may be modulated by congeners. Zinc, an essential component
      for living organisms, has been shown to counteract Ni effects in patients with Ni
      hypersensitivity. We analysed immune responses to both Ni and Zn in healthy
      subjects and patients with allergic contact dermatitis to Ni. Our in vitro
      results show that Ni modulates surface receptors expression, reduces
      phytohemagglutinin (PHA)-driven lymphoproliferation, and upregulates some
      proinflammatory cytokines production, including interferon (IFN)-gamma. Zn also
      induced CD4+ lymphocyte proliferation, but it abolished or reduced most Ni
      mediated effects. Our data are consistent with the hypothesis that Zn and Ni, as
      part of the heavy transition metals, may exchange roles in immune-mediated
      phenomena leading to expression of allergic contact dermatitis.

PMID- 14650624
TI  - Metal concentrations (Cu, Zn and Cd) and metallothionein expression in Sparus
      aurata exposed to waterborne copper.
AB  - Metal concentrations in different tissues of Sparus aurata are linked to the
      functional role of the investigated organ: in the liver, Zn and Cu are highly
      concentrated, due to the detoxification and storage processes typical of the
      hepatic tissue. Comparison between control specimens of farmed and wild gilthead
      seabream resulted in significant differences in Zn and Cu concentrations between
      the tissue metal levels of the two populations. The cadmium levels, always less
      than 1 microg/g wet weight, were indicative of a low exposure to the non
      essential element. In Cu-exposed fish the metal was mostly accumulated in the
      liver and to a lesser extent in the gills in a dose-dependent manner, whereas
      zinc concentrations were unaffected by the metal treatment. In the liver a 1.6
      fold and 4-fold increase was observed in fish exposed to 0.1 microg/mL and 0.5
      microg/mL respectively; moreover, Cu exposure caused an increase of MTmRNA and
      CuMT. On this basis, the two molecular parameters could be considered as useful
      biomarkers of an early cellular response against Cu toxicity.

PMID- 14650625
TI  - Protective effect of human HDL against Cu(2+)-induced oxidation of astrocytes.
AB  - Several studies support the role of copper-mediated oxidative injury in the
      development of neurodegenerative diseases. In this study we demonstrated that
      copper exerts an oxidant effect on cultured astrocytes as shown by the
      significant increase in the levels of hydroperoxides in astrocytes oxidized with
      10 micromol/L Cu2+ for 4 h with respect to control cells. Using the fluorescent
      probe 2,7-dichloro-dihydrofluorescein diacetate (H2DCFDA) that represents an
      useful approach for measuring the production of reactive oxygen species (ROS), a
      significant increase in fluorescence intensity was observed in Cu(2+)-oxidized
      cells. The increase in the levels of lipid peroxidation products was associated
      with a significant decrease in cell viability in Cu(2+)-treated cells with
      respect to untreated cells. Many evidences suggest that human high-density
      lipoproteins (HDL) play a key role against lipid peroxidation of plasma low
      density lipoproteins (LDL) and peripheral cells. We investigated whether HDL
      isolated from human plasma exert a protective role against copper-induced lipid
      peroxidation on astrocytes in culture. The increase in the levels of
      hydroperoxides and in the fluorescent intensity of H2DCFDA was significantly
      lower in astrocytes oxidized after preincubation for 20 h in the presence of HDL
      (50-200 microg/mL) with respect to cells preincubated without HDL. The decrease
      in viability in Cu(2+)-treated astrocytes preincubated with HDL was significantly
      lower with respect to cells preincubated without. These results demonstrate that
      preincubation of astrocytes with HDL for 20 h makes cells more resistant to the
      Cu2+ oxidant effect. The protective effect exerted by HDL against copper-induced
      oxidative damage on astrocytes was concentration dependent. These data suggest
      that copper, at concentrations similar to those observed in cerebro-spinal fluid
      of patients affected by neurodegenerative diseases, induces oxidative damage to
      astrocytes and confirm that HDL exert a protective effect against oxidative
      damage induced by copper ions.

PMID- 14650626
TI  - Toenail selenium as biomarker: reproducibility over a one-year period and factors
      influencing reproducibility.
AB  - We assessed the reproducibility of selenium levels in toenails, comparing
      concentrations in two sets of specimens collected about a year apart, from 80
      women (40 pre-menopausal and 40 post-menopausal) in the period October 1990 to
      February 1992. The women were participants in a prospective study on hormones and
      diet in relation to prediagnostic breast cancer (the ORDET study) conducted in
      northern Italy. Toenail selenium was determined by electrothermal atomic
      absorption spectrometry. The data were log-transformed as they were not normally
      distributed. To assess reproducibility Pearson correlation coefficients (r) for
      the two selenium determinations were calculated in pre- and post-menopausal
      women, according to smoking status and acetone treatment. A weighted kappa
      statistic (k) assessed inter-quintile agreement between the two sets of measures.
      Toenail selenium levels were highly reproducible (r = 0.57, p < 0.001),
      especially in pre-menopausal women (r = 0.66, p <0.001). Smoking lowered selenium
      levels (mean difference of 0.24 microg/g, p < 0.05 between smokers and non
      smokers) but did not significantly influence reproducibility. Acetone treatment
      to remove nail polish did not modify selenium levels but affected inter-quintile
      agreement, with moderate agreement (k = 0.58, p < 0.001) when acetone was used at
      both or neither samplings; and fair non significant agreement (k = 0.39, p =
      0.06) when acetone was used at one sampling but not the other. As selenium levels
      in toenails are highly reproducible, notwithstanding variation in selenium levels
      in food and long-term changes in individuals' food choices, toenail selenium may
      be a useful biomarker of selenium exposure, particularly since toenail samples
      provide a measure of long-term exposure. However age, smoking status and acetone
      treatment are possible causes of misclassification.

PMID- 14650627
TI  - Relationship between mineral content of domestic hot water and microbial
      contamination.
AB  - The relationship between Legionella and Pseudomonas spp contamination and mineral
      content of domestic hot waters was investigated in a cross-sectional Italian
      survey. Pseudomonas spp contamination was associated with elevated Ca, but lower
      Fe and free chlorine content in the water. Waters with Cu concentrations > 50
      microg/L prevented Legionella spp colonisation (OR = 0.14, 95% CI = 0.02-1.13),
      whereas the risk of legionellae occurrence increased in waters with Mn levels > 3
      microg/L (OR = 2.37, 95% CI = 1.06-5.30). Furthermore, Mn was positively
      associated with the risk of colonisation by eterotrophic bacteria growing at
      either 22 and 36 degrees C. Legionella species and serogroups were differently
      distributed according to Cu and Mn concentrations, suggesting that Legionella
      strains may have a different sensibility/resistance to trace elements. A specific
      action of Cu as decontamination factor is suggested and the consideration of Mn
      as a risk indicator for bacterial colonisation and biofilm presence is proposed.

PMID- 14650628
TI  - Element concentrations in Chianti Classico appellation wines.
AB  - The concentrations of 21 elements (Al, B, Ba, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na,
      Ni, P, Pb, S, Si, Sr, Ti, V and Zn) were determined in wine samples of the very
      popular Italian Chianti Classico appellation, vintage 1997. Concentrations of
      most elements in Chianti Classico wines fell in the range of European red wines.
      Data variability (expressed as a coefficient of variation, CV) was maximum for
      elements more prone to exogenous contamination such as Cu (a residue of vineyard
      treatments; CV = 165), Pb (from atmospheric contamination; CV = 99) or Ni (from
      wine-making contamination; CV = 78). With respect to the results of a previous
      survey on 1987 vintage wines (n = 24) from the same appellation, levels of Mn,
      Cr, Pb and Cd decreased by a factor of 1.65, 1.84, 2.67, and 3.00, respectively.
      The improved quality and standard of hygiene in wine-making, and the phasing out
      of leaded gasoline during the last decade are probably responsible for these
      results. No differences were found for Al, Mg, Fe and Zn. The principal component
      analysis successfully distinguished Chianti Classico wines from Chianti and
      Venetian Cabernet Sauvignon, which were analysed for comparison. Seven elements
      (Al, Mg, Ca, K, Sr, Mn and Si) described a distinctive pattern. The
      classification success rate was lower for the two Tuscan wines because of
      similarities in the growing environment and variety composition. However, several
      elements appear as important chemometric parameters for developing a specific
      system to protect the designation of origin of Chianti Classico wines.

PMID- 14650629
TI  - Biomonitoring of trace element air contamination at sites in Campania (Southern
      Italy).
AB  - Surface soils and one-year-old Quercus ilex L. leaves were investigated for
      element concentrations to evaluate the air quality of some sites in Campania
      (Southern Italy). Sampling was carried out at 7 natural and 7 urban sites from
      September 1998 to February 1999. The investigated elements were Cd, Cr, Cu, Fe,
      Mn, Ni, Pb, V and Zn. At the urban sites, Cr, Cu, Fe, Ni and Pb Leaf
      concentrations were on average two fold higher than at the natural sites. Cu, Pb
      and Zn soil concentrations were also higher at the urban sites. On the contrary,
      Cd, Cr and Mn soil concentrations were significantly lower than at the natural
      sites. Leaf and soil element concentrations were positively correlated for Cu and
      Pb, and negatively correlated for Cr. Both leaves and soil element accumulations
      showed a conspicuous deposition of Cu, Pb and Zn at the urban sites of Campania.

PMID- 14650630
TI  - Environmental discrimination of wines using the content of lithium, potassium and
      rubidium.
AB  - 56 wine samples were analysed to determine their content of Li, K and Rb. These
      samples came from 28 species of vine grown on two plots of land, each of which
      had different pedo-climatic characteristics. The data collected were elaborated
      using Linear Discriminant Analysis (LDA); this statistical approach showed that
      it was possible to net differentiate both the soil where the different species of
      vines were grown and the colour of wines. The variable "species of vine
      nationality", instead, has not been discriminated by LDA. These results point out
      that it is possible to identify the place of origin of wines and that the
      "environment" variable prevails over the others, using the content of Li, K and
      Rb.

PMID- 14650631
TI  - Stress-induced injuries and trace element concentrations in vascular leaf plants
      from an urban environment (Palermo, Italy).
AB  - We examined leaf injuries and measured trace element concentrations in vascular
      plants from an urban ecosystem with distinct stress valences (the city of
      Palermo), and compared them with samples of the same species from sites where the
      stress potential is lower. Urban pollution influences macro-, micro- and toxic
      element concentrations in leaves. Therefore these leaves can be used as markers
      of the chemical and biological effects of atmospheric pollution. We studied the
      trace element content in the leaves of two species, oleander and oak, both fairly
      tolerant plants and good indicators and bio-monitors of pollution contaminants.
      Samples were collected at various sites in different periods.

PMID- 14650632
TI  - Changes in soil and leaf trace element concentrations: a study in Naples city
      centre.
AB  - The spatial and temporal changes of trace element concentrations in leaves and
      soils of an urban area were investigated simultaneously. For this purpose, in May
      and September 2001 and in January and May 2002, samples of Quercus ilex leaves
      and surrounding soils were taken at 5 sites in central Naples and on Mt.
      Vesuvius, a remote area, as control. The contents of Cd, Cr, Cu, Fe, Mn, Pb, V
      and Zn were analysed in both matrices by atomic absorption spectrometry. The
      urban sites in Naples showed different spatial trends of contamination depending
      on each element. The highest leaf concentrations of Cr, Cu, Fe, Pb, V and Zn were
      measured at the sites affected by a high traffic flow. The highest Cd, Cu, Pb and
      Zn soil concentrations were measured at different urban sites. The remote soil
      showed the highest values of Cr and V. The significant correlations between Pb
      and Zn in each matrix and between leaf and soil Pb and Zn concentrations suggest
      a common origin and an influence of wet and dry airborne deposition upon foliage
      and soils. Cd, Pb and Zn concentrations decreased and Cr increased from May 2001
      to May 2002 in both matrices. The season and sampling period do not seem to
      affect trace element concentrations of Q. ilex mature leaves.

PMID- 14650634
TI  - Lossless compression of otoneurological eye movement signals.
AB  - We studied the performance of several lossless compression algorithms on eye
      movement signals recorded in otoneurological balance and other physiological
      laboratories. Despite the wide use of these signals their compression has not
      been studied prior to our research. The compression methods were based on the
      common model of using a predictor to decorrelate the input and using an entropy
      coder to encode the residual. We found that these eye movement signals recorded
      at 400 Hz and with 13 bit amplitude resolution could losslessly be compressed
      with a compression ratio of about 2.7.

PMID- 14650633
TI  - Comparison of two spatially resolved NIRS oxygenation indices.
AB  - We compared the percentage haemoglobin oxygenation indices from two near infrared
      spectrophotometers (NIRS) to determine whether the devices reported similar
      changes in response to induced changes in oxygenation. METHODS: 24 healthy
      juvenile swine undergoing cardiac bypass surgery had INVOS 5100 and NIRO-300
      sensors applied to the brow. Induced events included circulatory arrest, altered
      blood flow rate, core cooling, and re-warming. RESULTS: The average data
      collection was 4 hours 36 minutes and had an r = 0.82 mean correlation between
      the INVOS and NIRO. The total resting baseline collection from all trials (8,590
      pairs) had a correlation of r = 0.62. The average relationship between the INVOS
      and NIRO was non-linear: an INVOS regional oxygen saturation index (rSO2) of 0%
      was equivalent to a NIRO tissue oxygenation index (TOI) of 36.2%; values were
      equal at 56.8%; and an (rSO2) of 100% was equivalent to a TOI 85.9%. There was
      good or excellent agreement (r > 0.5) between the (rSO2) and TOI patterns of
      change during induced events in 96% of trials. The INVOS and NIRO were most
      closely correlated when an attenuation filter was used to obtain identical
      emitter/detector separations. CONCLUSIONS: There was close agreement between the
      INVOS 5100 and NIRO-300 in response to major physiological change, although
      absolute values of (rSO2) and TOI were not identical. There was less agreement
      during baseline measurements or minimal physiologic change.

PMID- 14650636
TI  - How to develop a low cost, in-house distance learning center for continuing
      medical education. Part I.
AB  - Continuing medical education is essential to improve the quality of health care.
      Residential courses are expensive for small hospitals but videoconferencing is an
      economical alternative. Models of distance learning centers are described along
      with an explanation of INTERNET basics and the use of INTERNET protocol for local
      area networks (INTRANET). Hardware, software and other technology required and
      the advantages and disadvantages of different communication methods are reported.

PMID- 14650635
TI  - Comparison of local measurement of cerebral metabolism and to cerebral PvO2
      during alterations in intracranial pressure, PaCO2 and arterial pressure--an
      experimental study in goat.
AB  - OBJECTIVE: to assess the changes in local brain PO2, PCO2, pH (PO2br, PCO2br,
      pHbr) measured by a intraparenchymal probe (Neurotrend, Codeman) and compare them
      to simultaneous recording of cerebral PvO2 and blood flow (CBF). METHODS:
      Arterial, venous longitudinal sinus blood samples and CBF were analyzed in 8
      adult anesthetized, ventilated goats. Three step increase of intracranial
      pressure (ICP) (16, 22, 29 mm Hg) were performed by inflation of an epidural
      balloon. At each ICP level, similar changes in MAP and in PaCO2 were performed.
      RESULTS: At constant PaCO2 and MAP, balloon inflation induced a fast response: a
      decrease of PO2br, PCO2br and pHbr (starting 14 +/- 12 sec, 45 +/- 23 sec and 55
      +/- 19 sec after the peak ICP, respectively). Since the second inflation level,
      PO2br decreased (p < 0.05) despite an ICP returning at 22 mm Hg and a cerebral
      perfusion pressure (CPP) larger than 90 mmHg. During changes in PaCO2, PO2br
      paralleled CBF and PvO2 before the second balloon inflation but diverged at
      higher ICP. In the same time pH-pHbr gradient rose. Hypotension did not induce
      sizeable changes. CONCLUSIONS: The direct metabolic monitoring of cerebral tissue
      locally compressed show fast response. At steady state, it shows alterations
      which are not detected by the measurement of the oxygen saturation in the
      longitudinal sinus or that of CBF. It confirms that the threshold for ICP which
      may require therapy in presence of focal brain compression is around 20 mm Hg
      even in the presence of a CPP > 90 mm Hg.

PMID- 14650637
TI  - How to develop a low cost, in-house distance learning center for continuing
      medical education. Part II.
AB  - The first part of this paper discussed the advantages and communication tools
      needed to create a Distance Learning Center for continuing medical education by
      using an Intranet or the Internet. This part continues with an explanation of the
      hardware, software (largely free) and human resources needed for
      videoconferencing as well as the costs. Suitable even for small hospitals
      Distance Learning Centers can be of higher quality than traditional methods of
      continuing medical education.

PMID- 14650638
TI  - Integrated image analysis solutions for PET datasets in damaged brain.
AB  - OBJECTIVE: To identify and discuss the problems inherent in the processing of
      multiparametric functional imaging datasets from patients with acute brain
      injury, using "triple oxygen" positron emission tomography (PET) as an example.
      To present an integrated imaging solution for analysis of such datasets and
      report on its use in practice. METHODS: Structured analysis of the steps in image
      analysis for triple oxygen studies in patients with acute brain injury,
      subarachnoid haemorrhage and carotid artery disease was undertaken. Systematic
      identification of the drawbacks of conventional manual processing techniques,
      which make use of modules from different commercially available software packages
      was carried out. This analysis informed the construction of an image analysis
      gateway that addressed these issues. RESULTS: We describe an integrated image
      analysis gateway (PETAn) that provides for the automated integration of all
      processing steps, along with outputs that detail analysis stages, error logs and
      results. Implementation of PETAn allowed batch processing of clinical PET data
      sets, reduced the level of technical expertise required for analysis, improved
      the quality of results and achieved significant reductions in operator analysis
      time. CONCLUSIONS: While modules from several imaging software suites can be
      usefully combined to allow analysis of multiparametric PET data sets from
      patients with acute brain injury, sequential use of these modules for various
      steps in image analysis is fraught with difficulty. Careful automation and
      integration of these steps greatly facilitates the interrogation of information
      rich data sets and increases research productivity.

PMID- 14650639
TI  - Mismatched concepts in a neonatal intensive care unit (NICU): further issues for
      computer decision support?
AB  - BACKGROUND: Common concepts and definitions are important for the effective
      practice of medicine. In an intensive care unit clear understanding of
      terminology and communication between different staff groups may be critical for
      optimal care. If computerised decision support tools are to be successfully
      deployed in these high intensity environments, all staff must understand the
      concepts and information that is to be portrayed. OBJECTIVE: To examine the
      similarity of language and concepts related to newborn infants and their care in
      staff groups with different experience. METHODS: An experimental study in a
      tertiary regional neonatal intensive care unit involved 32 staff in 4 groups with
      varying experience (junior and senior / nurses and doctors). A psychologist
      developed a lexicon of clinical actions and a second lexicon of possible patient
      descriptors applicable to newborn infants receiving all degrees of neonatal care
      by conducting interviews with staff on the unit. Card sorting experiments were
      performed on the terms in the action and descriptor lexicons, the staff being
      asked to group words that were related to the same or similar concepts. The card
      sort data were analysed using conventional cluster analysis to produce tree
      diagrams or dendrograms and then by distance matrix analysis to give cumulative
      probability plots. RESULTS: Differences were shown in the way various classes of
      staff and staff with different experience mentally map clinical concepts.
      Clinical actions were grouped more randomly by nurses and by those with less
      experience with a polarisation between senior doctors and junior nurses.
      Descriptors were classed more definitively and similarly by junior and senior
      nurses and senior doctors but more randomly and quite differently by junior
      doctors. Thus there were differences seen between nurses and doctors with
      different roles within the unit and differences related to experience.
      CONCLUSIONS: Concepts are used differently by various staff groups in a neonatal
      unit: this may have an impact on the effectiveness of computerised decision aids
      unless it is taken into account during their development.

PMID- 14650640
TI  - Does the EEG during isoflurane/alfentanil anesthesia differ from linear random
      data?
AB  - OBJECTIVE: Bispectral analysis of the electroencephalogram (EEG) has been used to
      monitor depth of anesthesia. In the majority of publications this has been done
      using the so called Bispectral (BIS) Index. The exact relation of this index to
      bispectral quantities like the bispectrum and its normalized version the
      bicoherence has not yet been published. In case the EEG is a linear random
      process the bicoherence is trivial. It is a mere constant independent of the EEG
      frequency. If the signal is a linear Gaussian random process this constant is
      zero. In this case both the bispectrum and bicoherence are zero. The aim of this
      study was to determine the proportion of EEG epochs with non-trivial bicoherence
      during anesthesia with isoflurane/nitrous oxide. METHODS: We reanalyzed 26.4 hr
      of EEG signal recorded in 8 patients during anesthesia for general abdominal
      surgery which were stored in digitized form on CD-Rom. The test developed by
      Hinich for Gaussianity and linearity was applied to these data. The test was
      validated with various kinds of surrogate data; especially the phase randomized
      (pr) EEG, synthetic Gaussian random data and the z-component of the Lorenz
      attractor and its pr version. RESULTS: The proportion of epochs for which a non
      trivial bicoherence was detected by the test was as follows: Lorenz data 95%, pr
      Lorenz data 5%, synthetic Gaussian data 13.8%, pr EEG 5.4%, original EEG 6.2%.
      CONCLUSION: As expected the test procedure correctly identified for the Lorenz
      data for 95% of all epochs a non-trivial bicoherence. For the original EEG data
      we could not find a significant greater percentage of epochs with non-trivial
      bicoherence than for the pr data and the synthetic Gaussian data. We conclude
      that the EEG during anesthesia with isoflurane/alfentanil appears to be largely a
      linear random process.

PMID- 14650641
TI  - Sigh: tool to determine the respiratory viscoelastic properties.
AB  - OBJECTIVE: In mechanically ventilated patients a high fraction of the pressure
      can be dissipated to overcome the viscoelastic components of the respiratory
      system. Recently it was demonstrated that sigh improved oxygenation in
      mechanically ventilated ARDS patients. We evaluated if, in acute lung injury
      (ALI) patients, the sigh can be used to measure the respiratory viscoelastic
      properties. METHODS: Ten consecutive normal subjects undergoing general
      anaesthesia for minor abdominal surgery and ten ALI patients admitted to the ICU,
      were studied. Three sighs were administered every minute during the measurement
      period. The viscoelastic constants (E2, R2 and tau2) were determined by (i) a
      series of end-inflation airway occlusions (multiple breath method, MBM) and (ii)
      fitting the time course of the slow decay in pressure during end inspiratory
      pause of the sigh (sigh method, SM). The results were compared by means of the
      limits of agreement as modified for small sample sizes. RESULTS: Viscoelastic
      parameters were similar to those obtained in other studies. In normal subjects
      the mean differences (+/- SEM) of tau2, R2, and E2 given by the SM and the MBM
      were 0 +/- 0.04 s, 0.37 +/- 0.20 cmH2O L(-1) s, and 0.21 +/- 0.26 cmH2O L(-1),
      respectively. The mean differences (+/- SEM) of tau2, R2, and E2 in ALI patients
      were 0.02 +/- 0.02 s, 0.45 +/- 0.31 cmH2O L(-1) s, 0.34 +/- 0.36 cmH2O L(-1),
      respectively. No lack of agreement could be detected between the two methods in
      all variables in normal subjects and ALI patients. CONCLUSIONS: The long
      inflation time characteristic of the sigh allowed the determination of the
      viscoelastic constants by means of a simpler and faster method. Moreover it does
      not require very small tidal volumes, which can increase reabsorption atelectasis
      in ALI patients and can improve alveolar recruitment and oxygenation in these
      patients.

PMID- 14650642
TI  - Thrombus formation in the left atrial appendage in the course of atrial
      fibrillation.
AB  - BACKGROUND: Thromboembolism in patients with nonvalvular atrial fibrillation is
      secondary to emboli arising from atrial cavities, particularly left atrial
      appendage. Stroke Prevention Atrial Fibrillation (SPAF) III study showed washing
      flow, left appendage ejection fraction, natural echocontrast, and left appendage
      volume and morphology, as risk parameters of thromboembolism. METHODS: The
      authors examined 69 patients by transesophageal echocardiography, subdividing
      them into 3 groups: 26 patients in sinus rhythm in Group A (Gr.A), 22 patients in
      atrial fibrillation without thrombi in the left atrial appendage in Group B
      (Gr.B), 21 patients with tromboembolism and with thrombus in the left atrial
      appendage (Gr.C). RESULTS: Atrial volume in sinus rhythm (SR) patients (41.9 +/-
      23.4 cm3) was lower than the one in Gr.B (86.2 +/- 47.9 cm3, p < 0.001) and Gr.C
      (78.6 +/- 28.5 cm3, p < 0.01), whereas no difference was found between Gr.B and
      Gr.C (86.2 vs. 78.6 cm3; p > 0.05). No difference was found between Gr.A and Gr.B
      left atrial appendage fraction (31.8% versus 29.1%, p > 0.05), whereas it was
      found related to Gr.C (31.8% versus 15.4% p < 0.01). Flow velocity within left
      atrial appendage was significantly higher in Gr.A in relation to the other two
      groups (p < 0.001); flow velocity in Gr.B was lower than in Gr.A but higher than
      in Gr.C and in all cases such differences were statistically significant (p <
      0.001). Gr.A flow duration was approximately twice as much compared to the one in
      Gr.B (616.8 +/- 94.1 msec vs. 483.3 +/- 172.6 msec, p < 0.01), whereas it was
      approximately four times higher compared to the one in Gr.C (616.8 +/- 94.1 msec
      vs. 165.7 +/- 53.7 msec; p < 0.001). Such duration, if related to the
      corresponding cardiac cycle, indicates the percentage of time during which blood
      flows through a cycle within the left atrial appendage; this value is about 85%
      of cardiac cycle in Gr.A, while it is 65% in Gr.B (p < 0.01) and about 21% in
      Gr.C (p < 0.001). CONCLUSIONS: Such results add a new parameter to the ones
      suggested in the SPAF III study for the evaluation of TE risk, that is flow
      duration measurement within the left atrial appendage, and its ratio to the
      cardiac cycle. The availability to measure this parameter, by recording the
      transesophageal pulse wave sample volume positioned in the atrial appendage,
      makes the evaluation of TE risk more reliable.

PMID- 14650643
TI  - Neurotensin pulmonary metabolism in normal and asthmatic subjects.
AB  - BACKGROUND: The role of pulmonary metabolism of endogenous neurotensin (NT) in
      asthma is still unclear. Information on this subject in humans is scarce.
      OBJECTIVES: Evaluation of the pulmonary metabolism of the endogenous NT in
      asthmatic subjects during symptom-free periods and after a methacoline challenge
      test and in healthy individuals. METHODS: Ten asthmatic subjects (aged 34 to 70
      years), diagnosed with extrinsic (n = 5), atopic (n = 3), and mixed asthma (n =
      2), were compared to a group of 10 healthy individuals (aged 45 to 69 years). The
      asthmatic group of patients was evaluated with a PD20-FEV1 methacoline challenge
      test 3 days after a washout period from cessation of their regular medications.
      Two catheters were inserted in order to draw blood samples for the evaluation of
      NT concentration: one was inserted into the pulmonary artery and the other into
      the radial artery. The mean concentration of NT in pulmonary and systemic
      arterial blood, as well as the arteriovenous difference of NT and the absolute
      value of production rate [PR/m'], PR/m'/kg and PR/m'/m2 were calculated for each
      participant. RESULTS: The mean neurotensin concentration in normal subjects was
      higher in mixed venous blood (pulmonary artery) than in systemic arterial blood
      (p < 0001). Similarly, mean NT mixed venous levels in asthmatic subjects was
      shown to be higher than mean NT levels in systemic arterial blood, before and
      after the bronchoconstriction with methacoline (p = 0.05 and p = 0.02,
      respectively). In contrast, the arterovenous difference and the mean values of PR
      of NT were similar in both groups. CONCLUSIONS: Our findings suggest that (1) NT
      concentration in mixed venous blood changes in transit through the pulmonary
      parenchyma, indicating that the pulmonary parenchyma is an important site of NT
      metabolism; (2) Pulmonary clearance of NT is unaffected by cholinergic
      bronchoconstriction. Further clinical studies are needed in order to improve both
      the understanding and the therapeutic approach of the neurogenic process in
      asthmatic subjects.

PMID- 14650644
TI  - Hyperhomocysteinemia in preeclampsia is associated to higher risk pressure
      profiles.
AB  - Homocysteine levels have been determined with Chromatography on HPLC column,
      between the 20th and the 24th week of pregnancy, in women with analogous
      characteristics (a) normotensive, (b) with pregnancy-induced hypertension (PIH),
      low (LR), medium (MR), high risk (HR). The group they belonged to was confirmed
      after natural or caesarean delivery. All the patients were submitted to 24 hour
      blood pressure monitoring for the evaluation of further pressure risk parameters:
      mean arterial pressure (MAP), non dippers, percentages of pressure peaks.
      Homocysteine levels in normotensive pregnant women (5.8 +/- 1.7 microM) were low.
      Significant high levels of homocysteine were present proportionally to the risk
      degree of PIH. Higher levels of homocysteine statistically significant were
      present in non dippers of all groups (MR p < 0.05; HR p < 0.01). A direct
      correlation between plasmatic homocisteine levels and pressure profiles was found
      out in non dippers (r = 0.56, r = 0.55, r = 0.50 respectively) and in dippers (r
      = 0.7, r = 0.75, r = 0.60 respectively), and also between levels of homocysteine,
      MAP value, and pathological percentages of systolic and diastolic nocturnal
      peaks. In pregnant women presenting preeclampsia afterwards, high levels of
      homocysteine were not different from mean values present in high risk PIH
      pregnant women (13.3 +/- 1.9 vs. 16.4 +/- 1.7 microM). High levels of
      homocysteine early determined in the second trimester of PIH pregnancies seem to
      be associated to a pregnancy higher risk, coexisting with dangerous pressure
      profiles. High levels confirm a pregnant woman to belong to a higher or lower
      risk degree of vascular damage, but in the same group context high levels of
      homocisteine do not allow to identify those pregnant women who will develop
      eclampsia.

PMID- 14650645
TI  - Use of mental health and substance abuse services among high-cost Medicaid
      enrollees.
AB  - Users of mental health and substance abuse (MH/SA) services were examined among
      nonelderly high-cost Medicaid enrollees in 10 states in 1995. Although MH/SA
      service users constitute 11% of all Medicaid enrollees, they make up nearly a
      third of high-cost enrollees. Adults account for two thirds of this high-cost
      MH/SA group, and most frequently qualify for Medicaid through disability-related
      eligibility categories. In contrast, a majority of children in the high-cost
      MH/SA group are eligible for Medicaid through child-related categories, rather
      than disability. In diagnostic makeup, the high-cost group was somewhat more
      likely to have serious disorders than the general Medicaid MH/SA user population.

PMID- 14650646
TI  - Predicting length of stay on an acute care medical psychiatric inpatient service.
AB  - The goal of this study was to identify variables associated with length of stay
      (LOS) and to incorporate into the authors' routine preadmission assessment the
      measurement of these variables. A retrospective study of 80 discharged patients
      explored the association of 25 variables reflecting a mixture of
      patient/demographic variables, illness variables, and treatment variables with
      LOS. Multivariate analysis revealed that 10 variables independently accounted for
      62% of the variance in LOS. The information used was obtained primarily in the
      preadmission screening. The predictive power of the variables shrank in the
      prospective study. However, fewer individual variables were significantly
      associated with LOS; the summed score of the variables predicted 17% of the LOS
      variance. Results indicated that factors important for estimating LOS are
      available at the time of admission, and these variables can be systematically
      assessed and incorporated into clinical decision making.

PMID- 14650647
TI  - Change in mental health service delivery among blacks, whites, and Hispanics in
      the Department of Veterans Affairs.
AB  - The authors analyzed changes in access to and use of mental health services by
      minorities in the Veterans Health Administration during a period of major system
      change (1995-2001). Blacks had poorer outpatient access than Whites during this
      period of change, but were not further disadvantaged over time, and their access
      to care improved relative to Whites on some measures. For Hispanics, there was a
      trend toward greater inequality in the delivery of outpatient mental health care.
      These results suggest a need to monitor and address the differential impact on
      minorities of changes in mental health service delivery.

PMID- 14650648
TI  - What happens to patients' psychotropic prescriptions after discharge from a state
      psychiatric hospital?
AB  - Continuity of pharmacotherapy was examined between a state psychiatric hospital
      and an urban community mental health center. Anecdotal reports from
      administrators as well as limited empirical research suggested that there would
      be breaks in the continuity of pharmacotherapy across the two agencies and that
      the high cost of newer medications would contribute to poor continuity. Clinical
      chart reviews of 242 discharges over a 5-year period revealed that less than 11%
      of atypical prescriptions and less than 20% of all psychotropic prescriptions
      were altered beyond dosage level changes after discharge from a state hospital.
      Analysis of reasons given (reported) for altering the medication regimen revealed
      a consistent pattern of changes based on clinical evidence or consumer choice.

PMID- 14650649
TI  - Four decades of mental health policy in Ontario, Canada.

PMID- 14650650
TI  - Relationship of depression and anxiety to cancer patients' medical decision
      making.
AB  - The purpose of this study was to examine the relation of depression and anxiety
      to cancer patients' medical decision-making. Participants were 79 rural and urban
      cancer patients undergoing chemotherapy. The four decisional styles of the
      Decisional Processing Model were the independent variables. Dependent variables
      were anxiety and depression, measured by Spielberger's State-Trait Anxiety and
      the Center for Disease Control Depression Scale, respectively. Consistent with
      the Decisional Processing Model, analysis suggested that patients make medical
      decisions by information seeking, information processing, advice following, or
      ruminating. Decisional style did not vary according to type or stage of cancer,
      prognosis, time elapsed since initial diagnosis, or whether cancer was initial or
      recurrent. Decisional style did not systematically vary with depression and
      anxiety suggesting how a person makes decisions is a stable personality trait.
      Thus, decision-making may follow a cognitive schema. It is likely that patients'
      decisional styles help to manage anxiety and depression when confronted with life
      threatening illness. Implications for informed consent and patients' involvement
      in decision-making are discussed.

PMID- 14650651
TI  - Toward a career development model for postbaccalaureate premedical programs: from
      theory to practice.
AB  - The purpose of this study was to assess the career maturity of 168 minority and
      disadvantaged premedical students upon entry into a medical education preparatory
      program. All took the Medical Career Development Inventory as a pre-assessment in
      the course. Students' scores identified three instructional groups: on, below,
      and above instructional level. A model for career intervention for
      postbaccalaureate premedical programs is presented.

PMID- 14650652
TI  - Signal probability effects on error detection performance in a quality control
      task.
AB  - This study was designed to examine the influence of signal probability on
      detection accuracy in a quality control task patterned after the checking of
      prescriptions in a pharmacy. Signal probability was defined as the ratio of
      erroneous scripts to correct scripts. 91 participants were either exposed to
      signal probabilities ranging from 26 to 30% ("low probability") or 34 to 38%
      ("high probability") while checking two sets of 40 simulated scripts for
      accuracy. Wrong item, wrong number, and wrong label information errors were
      possible, and performance was measured in terms of sensitivity (percentage of
      errors detected) and specificity (percentage of correct orders accepted).
      Analysis indicated that sensitivity was significantly worse for participants in
      the high signal probability condition, but specificity was not significantly
      different between signal probability conditions. Connections to existing theory
      and future directions for research are discussed.

PMID- 14650653
TI  - Present mood states in Brazilian night nurses.
AB  - Variations in the state of momentary emotions of Brazilian hospital nurses on day
      and night shifts were recorded. Ten graduate nurses working on day and night
      shifts in the clinical ward of hospitals completed the Present Mood States List
      of Engelmann at the beginning and end of the first and last days of each shift.
      Analysis indicated (a) nurses had a stable emotional profile, present at the
      working shift, and (b) variations in present mood states related to specific
      effects of shift work were observed when comparisons were made between the
      present mood states at the beginning and end of each shift duty.

PMID- 14650654
TI  - A factor analysis of Furnham's Money Attitude Scale: a response to Furnham.
AB  - Two empirically-derived scales from Furnham's Money Attitude Scale are presented.
      They measure money as a source of status and power and having a strong desire for
      money.

PMID- 14650655
TI  - Validation and measurement of perceived environmental threat as an antecedent to
      job insecurity.
AB  - The Perceived Environmental Threat scale was designed to measure perception of
      environmental sources of threat to an individual's job. A total of 276 managers
      responded to a survey to test the psychometric characteristics. Analysis
      supported the internal reliability and factor structure and anticipated
      correlations were observed with two measures of job insecurity. The Perceived
      Environmental Threat scale also demonstrated convergent validity as scores
      correlated positively with those on Anticipated Organizational Change which,
      generally, did not correlate significantly with trust, commitment, or role
      ambiguity, variables with which it was not expected to be related. The evidence
      was generally supportive of the overall psychometric properties, offering
      academic researchers and managers a useful means of evaluating perceived
      environmental threat.

PMID- 14650656
TI  - A case-control analysis of felony convictions among recreational drug users.
AB  - This study applied an epidemiologic case-control design to the identification of
      variables predicting which subjects in a population of recreational drug users
      were likely to have a felony conviction. A sample of 158 self-identified drug
      users responded to the web-based DRUGNET survey from February, 1997 through June,
      1998. In this sample of 704 U.S. citizens who reported using illicit drugs, 79
      (11.2%) reported having a drug-related felony conviction. A further 52 (7.4%)
      subjects reported felony convictions not related to drugs. Control subjects were
      drawn from the same sample and matched to cases on sex, age, and ethnicity.
      Subjects with drug-related convictions differed significantly from controls on 13
      variables and those with nondrug-related convictions differed on 11 variables out
      of the 82 used in this study. Although there are major limitations given the self
      selection of the sample, the differences between the groups indicates that we
      should be wary in generalizing from the minority of drug users who are arrested
      or incarcerated to the population of drug users in general.

PMID- 14650657
TI  - Interpersonal problems and personality: using three factor solutions.
AB  - Attempting to bridge the gap between psychotherapy research on interpersonal
      discord and personality research on factors of normal and abnormal personality,
      the present study uses personality factors to predict interpersonal problems.
      Eysenck's P-E-N (Psychoticism-Extraversion-Neuroticism) model of personality and
      its correspondent index, the Eysenck Personality Questionnaire-Revised is used as
      a schema from which to conceptualize and measure personality. Horowitz's
      Inventory of Interpersonal Problems, which includes six problems commonly
      reported by psychotherapy patients at intake (hard to be assertive, hard to be
      submissive, hard to be intimate, hard to be sociable, too controlling, and too
      responsible), was used as an index of interpersonal distress. Hierarchical
      multiple regression, in which the most significant predictor was entered into the
      equation first, indicate significant prediction of various problems by the
      personality factors considered here. Results are discussed in the context of
      interpersonal theory.

PMID- 14650658
TI  - Correlates of motives for suicide.
AB  - Analysis of a large sample of suicide notes from 262 suicides in Australia showed
      separated/divorced suicides and suicides who abused alcohol were more likely to
      give love/romance as a precipitant for suicide while those who used gas (natural
      or car exhaust) were more likely to give depression and guilt as a motive.

PMID- 14650659
TI  - Supervisors' behavior during new employees' socialization: scale development.
AB  - This study developed a 16-item scale to measure specifically the construct of
      Intended Socialization Behavior of the supervisor during new employees'
      socialization. Data were collected from 178 subjects representing six midwestern
      organizations. The organizations ranged in size from 100 to 1,001+ employees and
      represented multiple industries. The subjects included 74 subordinates (with less
      than 1 year tenure at the organizations) and 93 supervisors. Both the subordinate
      and the supervisor groups were predominantly male, and the subordinate group was
      primarily younger than the supervisor group.

PMID- 14650660
TI  - Local processing bias impairs lineup performance.
AB  - Evidence suggests that lineup performance by witnesses can be influenced by
      inducing a prior local or global processing bias. In this study, 90 witnesses
      attempted to identify a perpetrator from a lineup. Prior to the lineup, 30
      participants completed a global processing task followed by a local processing
      task; 30 did the same tasks in reverse order; and 30 acted as controls. Analysis
      indicated that the last task completed influenced subsequent lineup performance.

PMID- 14650661
TI  - Intrinsic-extrinsic religious orientation and individual coping style.
AB  - The relationship between intrinsic and extrinsic religious orientation and the
      use of specific coping strategies was investigated among 58 volunteers who ranged
      in age from 17 to 57 years and who reported experiencing either high or low
      stress. Dependent upon the amount of stress, age interacted with religious
      orientation to influence the use of two coping strategies, turning against an
      object and turning against self.

PMID- 14650662
TI  - Predicting success among first-year engineering students at the Rand Afrikaans
      University.
AB  - 160 first-year students in the Engineering Faculty at the Rand Afrikaans
      University completed the Study Orientation Questionnaire in Mathematics and the
      Senior Aptitude Test Advanced. 100 students who passed and 40 who failed the
      first year scored significantly differently on three subtests, Calculations,
      Study attitude in mathematics, and Problem-solving behaviour in mathematics. Step
      wise linear regression showed a combination of three fields, namely,
      Calculations, Study attitude in mathematics, and Mathematics anxiety, contributed
      significantly (R2=25.8%) towards predicting the first-year aggregate score of
      first-year engineering students.

PMID- 14650663
TI  - Domestic violence among homosexual partners.
AB  - Is domestic violence more frequent in homosexual partnerships? The 1996 National
      Household Survey of Drug Abuse, based upon a random sample of 12,381 adults aged
      18 to 59 years, estimated that 828,900 men and 828,678 women engaged in
      homosexuality in the prior 12 months. Random surveys indicated that at any given
      time, 29% of homosexual men and 32% of homosexual women are in same-sex
      partnerships. The National Criminal Victimization Survey for 1993 to 1999
      reported that 0.24% of married women and 0.035% of married men were victims of
      domestic violence annually versus 4.6% of the men and 5.8% of the women reporting
      same-sex partnerships. Domestic violence appears to be more frequently reported
      in same-sex partnerships than among the married.

PMID- 14650664
TI  - Customers' perceptions of salespersons' orientation and susceptibility to
      salespersons' influence.
AB  - This study examined correlations of scores for salespersons' and customers'
      orientation, as indicated by a modified Salesperson Orientation-Customer
      Orientation scale, with self-reported consumers' susceptibility to salespersons'
      information, recommendations, and relational influence. Vehicle purchasers
      provided 508 useable survey responses. Correlations for customers' perceptions of
      both salespersons' orientation (-.39 and -.21) and customers' orientation (.39
      and .24) were related to self-reports of susceptibility to salespersons'
      information and relational influence.

PMID- 14650665
TI  - Family and ability correlates of academic achievement: social status group
      differences.
AB  - In a set of interrelated investigations in 2001-03, Garcia Bacete and Rosel
      Remirez, Marjoribanks, and Garcia Bacete and Villanueva Badenes examined
      relationships among intellectual ability, family environment, and academic
      achievement. Analysis in this follow-up study showed that relationships among
      ability, environment, and achievement varied for children from different social
      status groups.

PMID- 14650666
TI  - A quaternary temperament model and defense cluster preferences.
AB  - A quaternary model of temperament constructed from orthogonal axes defined by
      Extraversion-Introversion and Thinking-Feeling resulted in four groups:
      Introverted Thinking, Introverted Feeling, Extraverted Thinking, and Extraverted
      Feeling. Hypothesized relationships between quaternary groups and defense cluster
      preferences were tested by giving 158 female college students the Myers-Briggs
      Type Indicator and the Defense Mechanisms Inventory. There was little support for
      hypothesized relationships between the quaternary model and defense preferences.
      The only hypothesized significant group difference showed the Extraverted Feeling
      group recording a greater preference for the Reversal defense cluster than the
      Introverted Feeling group.

PMID- 14650667
TI  - Association of daytime sleepiness and the morningness/eveningness dimension in
      young adult subjects in Brazil.
AB  - Sleepiness is a major public health problem associated with motor vehicle
      crashes, occupational accidents, decreased productivity, and interpersonal
      problems. It can be influenced by many factors, including the individual's
      circadian rhythm. The objective of this study is to assess the correlation
      between the morningness/eveningness dimension and daytime sleepiness in medical
      school students. This is a cross-sectional study; 310 subjects (123 women and 187
      men, M age 20.5 +/- 1.9 yr.) completed a questionnaire on use of drugs,
      diagnostic diseases, sleeping habits, the Morningness/Eveningness Questionnaire
      and the Epworth Sleepiness Scale. The only variable related to daytime sleepiness
      was the morningness/eveningness dimension (r = -.18, p=.002). Questions with
      higher coefficients of discrimination between the morning and the evening
      chronotype were "Lying down to rest in the afternoon when circumstances permit"
      (.61), "Sitting and reading" (.53), and "As a passenger in a car for an hour
      without a break" (.53). The implications of the findings are discussed.

PMID- 14650668
TI  - The function of phenomenal states: is there progress for the "softer problem" of
      consciousness?
AB  - The function of phenomenal states remains a mystery, primarily because of the
      prevalent, a priori view that these states serve no functional role. This note is
      a call to arms against this uncorroborated and counterproductive view, which
      continues to stifle research on the topic. It is proposed that, given what we
      know and can accomplish with the tools at hand, discovering the function of
      phenomenal states has become a tractable problem, easier than that of discovering
      the neural basis of these states--the "hard problem" of consciousness. A simple
      method that may unveil the function of phenomenal states is presented. It
      involves contrasting the task demands of conscious and unconscious processes.

PMID- 14650669
TI  - A validity study of the Positive Psychology Protective Profile.
AB  - The purpose of this study was to conduct an exploratory factor analysis to
      provide support for the construct validity of the Positive Psychology Protective
      Profile, a self-report measure based on positive psychology. 985 undergraduates
      completed the profile, the Beck Depression Inventory, and the College Life Stress
      Inventory. Scores on the first two factor scores (Positive Outlook, Negative
      Symptoms) for the profile correlated significantly with scores on depression and
      stress, whereas scores on the third profile factor (Problem-solving) correlated
      significantly only with scores on the Beck Depression Inventory. Scores on the
      Positive Outlook significantly differentiated participants having either chronic
      illness or recent major illness from those who did not.

PMID- 14650670
TI  - Authoritarian and aggressive attitudes in American students.
AB  - In a sample of 118 college students, scores on a measure of authoritarian
      attitudes were associated with scores on subscales from the Buss and Perry (1992)
      Aggression Questionnaire.

PMID- 14650671
TI  - Assessment of thinking style preferences and language proficiency for South
      African students whose native languages differ.
AB  - The language proficiency of first-year students at the University of Pretoria (56
      men and 59 women, M age=19.40 yr., SD=.80, range from 18.00 to 20.70) was
      assessed by means of the English Language Skills Assessment. More than one-third
      of the students did not show proficiency at Grade 10, as expected. This language
      assessment was not correlated with academic achievement equally well for students
      in a group. The diversity of thinking style preferences of the students enrolled
      in a language development course was also assessed on the Herrmann Brain
      Dominance Instrument. Scores indicated a range of thinking style preferences but
      the group's overall mean scores represented detail-oriented and feeling-based
      modes of thinking processes. These preferences were correlated with academic
      achievement and learning of languages. The data are consistent with the
      hypothesis that thinking styles could be a focus of educational strategies in
      South Africa, using the perspective that qualitatively different approaches to
      teaching might be associated with students' qualitatively different approaches to
      learning.

PMID- 14650672
TI  - Problem behaviors and suicide and homicide.
AB  - In a sample of 36 nations, suicide rates were negatively associated with a drug
      abuse index. Homicide rates were positively associated with a violent crime
      index.

PMID- 14650673
TI  - Comparability of self-report checklist and interview data in the assessment of
      stressful life events in young adults.
AB  - The purpose of this study was to evaluate the incremental value of conducting an
      interview to assess stressful life events over the self-report questionnaire
      approach, first by examining the degree to which life events reported on a
      questionnaire met inclusion criteria in a detailed stress interview, and second,
      by comparing the magnitude of prospective associations with depression symptoms
      for the two different assessment procedures. Data from the Oregon Adolescent
      Depression Project were examined, in which 191 community-residing young adults
      (55% female; M age=23.6, SD=0.6) completed a mailed questionnaire assessing the
      frequency with which 33 life events had occurred to them or to other important
      people in their lives prior to the diagnostic and stress interviews. An average
      of 67.5% of events occurring to self met criteria for classification as a life
      event on the stress interview, as did 19.7% of the events occurring to others.
      Events having a large effect on the participant had a greater likelihood of
      meeting inclusion criteria on the stress interview. Contrary to expectation,
      stress scores from the interview assessment did not result in stronger
      associations with depression. Recommendations for assessment of stressful life
      events are offered.

PMID- 14650674
TI  - A statistical comparison of the apparent importance of various prophets within
      early Islamic and Christian historical documents.
AB  - Counts were made for the number of times prophets were mentioned in both the
      Qur'an and in the New Testament. Within the New Testament, the name Jesus (Isa)
      is cited far more than any other notable figure. Within the Qur'an, Moses is
      cited most often, followed by Abraham and Noah. Statistical analysis indicates
      that Jesus is cited between 4th and 11th most often among the prophets of Islam,
      which seemed surprising to the author, given that Jesus is considered to be the
      ultimate prophet by many Muslims.

PMID- 14650675
TI  - A mathematics content course and teaching efficacy beliefs of undergraduate
      majors in education.
AB  - This study was designed to assess the mathematics teaching efficacy beliefs of
      undergraduates in elementary education through a manipulative-based course in
      mathematics. Responses of 106 university undergraduates to the 21-item
      Mathematics Teaching Efficacy Beliefs administered as pre- and posttest without a
      control group showed a significant immediate postcourse change in their efficacy
      beliefs using dependent t test.

PMID- 14650676
TI  - Physicians' perceptions of compliance and attitudes toward complementary care.
AB  - 31 surveyed physicians perceived that between one-third and two-thirds of
      patients do not comply with instructions, and that nearly one-third of those who
      comply do not show optimal treatment response. The physicians expressed concerns
      about the validity and cost of complementary approaches that might increase
      medical compliance and enhance treatment response.

PMID- 14650677
TI  - Psychometric properties of the Children's Attributional Style Questionnaire.
AB  - The structure of the Children's Attributional Style Questionnaire was examined
      for 359 children in Grades 5 and 6. Unsatisfactory internal consistency
      reliabilities ranged from .19 to .41 for the subscales and .54 for the overall
      measure. In addition, scree plots of the individual subscales resulted in a range
      of 2 to 4 factors per subscale and hence lacked evidence of unidimensionality.

PMID- 14650678
TI  - How lonely are gay and lesbian youth?
AB  - UCLA Loneliness Scale (8-item version) scores in a sample of 384 gay and lesbian
      adolescents support the hypothesis that such youths are especially vulnerable to
      loneliness.

PMID- 14650679
TI  - Factors influencing the desire for children.
AB  - 187 college students (139 women; 175 between the ages of 18 to 25 years) were
      asked to report how many children they desired. Participants' desire for children
      was unrelated to skin color, socioeconomic status, and the need for
      postbaccalaureate education. Conversely, sex, value orientation, and religious
      orientation were significantly associated with a desire for children.

PMID- 14650680
TI  - Relationship with health care provider and adherence to HIV medications.
AB  - Suboptimal adherence to antiretroviral medications was reported in a sample of 97
      inner-city residents with HIV/AIDS. Most respondents had been seeing the same
      physician for several years. Those who perceived themselves to be more engaged
      with their health care provider also reported better treatment adherence. This
      finding, though, should be viewed with caution since self-reported measures were
      used. Interventions that target adherence could include patients' perceptions of
      providers.

PMID- 14650681
TI  - Cognitive Testing Battery: differences among groups with dementia, Huntington's
      disease, and controls.
AB  - This study evaluated a new test for dementia, the Cognitive Testing Battery, used
      for over six years in outpatient clinics for aging-related disorders. This
      battery was developed to be brief, easy to administer, and to provide useful
      feedback as a cognitive profile for clinicians, patients, and caregivers. 489
      participants were tested during a 5-yr. period. Multidisicplinary teams diagnosed
      these patients with dementia, depression, or Huntington's Disease. A control
      group was also included. Groups were then compared on the 10 key subscales that
      subserve dementia populations. Analysis showed there were significant differences
      among the groups on all measures and that selected scales differentiated the
      groups. The total score maximally differentiated the groups, and the dementia
      group was most different from the other groups.

PMID- 14650682
TI  - Contributions to the history of psychology: CXVIII. Michael Argyle, 1925-2002.
AB  - Recollections of Michael Argyle, one of Europe's leading social psychologists,
      cover his life, work, and some ideas.

PMID- 14650683
TI  - Mean Beck Depression Inventory-II scores of outpatients with dysthymic or
      recurrent-episode major depressive disorders.
AB  - The Beck Depression Inventory-II, published in 1996, was administered to 100
      adult outpatients (Age M=43.1 yr., SD=15.6) who were diagnosed with a recurrent
      episode Major Depressive Disorder and 100 outpatients (Age M=42.8 yr., SD=15.7)
      who were diagnosed with a Dysthymic Disorder. Each diagnostic group was composed
      of 50 men and 50 women who did not have a comorbid depressive disorder. The mean
      Beck Depression Inventory-II total score and the mean number of symptoms endorsed
      by the outpatients with a Major Depressive Disorder were significantly (ps<.001)
      higher than those for outpatients with a Dysthymic Disorder. The usefulness of
      the Beck Depression Inventory-II was discussed in helping clinicians discriminate
      between these two unipolar disorders.

PMID- 14650684
TI  - Interpreting past religious discrimination today.
AB  - Much of modern western law now presupposes opposition to discrimination based on
      race, religion, sex, national origin, and other factors. However, ancient
      religious Scriptures may have sanctioned certain types of discrimination. Whether
      those who are inclined to accept literal interpretations of their Scriptures will
      condone certain forms of discrimination could be evaluated to contrast the
      effects of modernization versus religious indoctrination on various kinds of
      prejudice.

PMID- 14650685
TI  - The original MMPI and Colligan Norms revisited.
AB  - Norms developed by Colligan, Osborne, Swenson, and Offord (1983) and others at
      the Mayo Clinic for the MMPI overcome criticisms that the MMPI is not useful in
      2003 and representative. This study ascertained the classification of MMPI
      profiles of clinicians. Mayo Clinic norms are warranted in view of the similar
      classifications made using both methods based on the same MMPI data.

PMID- 14650686
TI  - Methods of killing employed by psychotic parricides.
AB  - Lewis, et al. in 1998 showed that psychotic women are more likely to use a weapon
      than nonpsychotic women to kill their children. This study presents data
      concerning psychotic parricide. Analysis indicated that a higher percentage used
      a weapon (81% versus 36%) than psychotic filicide. Reasons for this difference
      are discussed.

PMID- 14650687
TI  - Changes in behavior and behavioral intentions among middle-age women: results
      from an osteoporosis prevention program.
AB  - The purpose of this study was to evaluate changes in behaviors and behavioral
      intentions that occurred among 342 middle-age women (M age 49.5 yr.) after
      participating in an Osteoporosis Prevention Program. The valid and reliable
      Osteoporosis Preventing Behaviors Survey (developed by Doheny and Sedlak) and a
      survey developed for this work were measures. Significant changes in behaviors
      were reported, especially increases in weight-bearing physical activity, dairy
      product intake, and decreases in consumption of caffeine-containing beverages.
      Many subjects reported intentions to increase physical activity and calcium
      intake. An Osteoporosis Prevention Program may help promote osteoporosis
      prevention behaviors, but intents must be followed up to check actual change.

PMID- 14650688
TI  - Death anxiety in Spain and five Arab countries.
AB  - The present study compared death anxiety among volunteer undergraduates from
      Spain and five Arab countries, i.e., Egypt, Kuwait, Qatar, Lebanon, and Syria.
      The Templer Death Anxiety Scale was used in its Spanish and Arabic forms,
      respectively. The Mean for the Spanish sample was lower than that of their Arabic
      counterparts in the five countries, whether the subjects were men or women.

PMID- 14650689
TI  - Hardy personality: a potential link with organizational citizenship behavior.
AB  - Hardiness is a personality construct which is assumed to protect the individual
      from stress-induced illness. Although widely accepted, hardiness has shown only
      modest relations with the development of illness. Examining the components of
      hardiness indicates apparent consistency with organizational citizenship
      behaviors such as obedience, participation, and loyalty. This study investigated
      the potential relations between hardiness and organizational citizenship
      behavior, using Kobasa's Personal Views Survey, and Van Dyne, Graham, and
      Diensch's citizenship measure. Subjects were 129 unionized employees whose mean
      age was 37 yr.; 58% were men. Correlations and regressions indicated that scores
      for total hardiness and its components of commitment and control were linked to
      citizenship behaviors. Differential relationhips were identified between
      hardiness and citizenship behavior for individuals with high versus low scores on
      hardy personality. Hardiness appears to have a positive association with
      organizational effectiveness through its link to citizenship behavior and
      consequently may have more implications for organizational behavior than for
      health.

PMID- 14650690
TI  - The Multidimensional Child and Adolescent Depression Scale: psychometric
      properties.
AB  - Based on previous factor analyses of child and adolescent depression inventories,
      the following eight basic dimensions were identified, i.e., Pessimism, Weak
      Concentration, Sleep Problems, Anhedonia, Fatigue, Loneliness, Low Self-esteem,
      and Somatic Complaints. Each dimension was assessed by five items, so the
      Multidimensional Child and Adolescent Depression Scale has 40 brief statements
      answered on a 3-point intensity scale, i.e., None, Some, and A lot. The eight
      dimensions have good factorial validity and acceptable to good alpha and test
      retest reliability, and good criterion-related validity using three self-report
      depression scales. The total scale score has from good to high coefficients of
      reliability and validity. The highest mean scores were on Fatigue and Anhedonia
      for Kuwaiti boys and girls, respectively, while the Loneliness subscale has the
      lowest mean score for both sexes. Girls attained significantly higher mean scores
      than boys for the total score as well as on all dimensions, with the exception of
      weak concentration. The scale has two compatible Arabic and English versions. It
      was designed to be useful in defining the profile of children's and adolescents'
      depression.

PMID- 14650691
TI  - Toxic mold and mycotoxins in neurotoxicity cases: Stachybotrys, Fusarium,
      Trichoderma, Aspergillus, Penicillium, Cladosporium, Alternaria, Trichothecenes.
AB  - Presented is the argument that psychologists and neuropsychologists have no
      scientific basis for rendering opinions about causation given the current state
      of the literature. The critical question is whether in a residence or office
      inhalation of mold spores or mold metabolites, including mycotoxins, causes
      neuropsychological impairment or mental and emotional disorders. There has not
      been sufficient research to support such conclusions. Nonetheless, in the context
      of litigation, speculative opinions are rendered in lieu of scientifically well
      founded conclusions. Resources for recognizing and coping with pseudoscientific
      arguments are suggested.

PMID- 14650692
TI  - Revised form of the Belief in Good Luck Scale in a Turkish sample.
AB  - The aim of the study was to explore the patterns of belief in luck in a Turkish
      sample. For this purpose, a shorter version of Freedman and Darke's Belief in
      Good Luck Scale was given, including some more items related to the beliefs in
      'consistent' versus 'variant' patterns of luck. This scale, together with Turkish
      versions of Rosenberg's measure of Global Self-esteem, Rotter's Internal-External
      Locus of Control Scale, and the Satisfaction With Life Scale of Diener, Emmons,
      Larsen, and Griffin, was administered to a group of 173 (96 men, 77 women)
      undergraduate students from the Middle East Technical University attending an
      elective general psychology course. The mean age was 21 yr. (SD=2.1). The factor
      composition of the extended scale consisted of three scales, similar to the
      original version. Loading of new items on the General Belief in Luck factor
      indicates that this factor may describe a belief in an organised pattern of luck.

PMID- 14650693
TI  - The effects of short- and long-term life review interview on the psychological
      well-being of young adults.
AB  - The present study investigates the effects of short- and long-term life review
      interviews on young adults' psychological well-being. Study 1 investigates mood
      using the Japanese UWIST adjective checklist (yielding two scores: Tense Arousal
      which represents low hedonic tone and Energetic Arousal which represents high
      hedonic tone). Results show that Energetic Arousal significantly increased after
      life review, although Tense Arousal did not change. Study 2 investigates self
      esteem and mental health (measured by the General Health Questionnaire-6 factors:
      General Illness, Somatic Symptoms, Sleep Disturbance, Social Dysfunction, Anxiety
      and Dysphoria, Suicidal Depression). Both self-esteem and mental health scores
      increased after life review. With regard to factors of mental health, General
      Illness and Anxiety Dysphoria scores were much higher than those on Somatic
      Symptoms, Sleep Disturbance, Social Dysfunction, and Suicidal Depression. There
      was also a significant difference between before and after scores on General
      Illness, Somatic Symptoms, Sleep Disturbance, and Anxiety Dysphoria, but not in
      Social Dysfunction and Suicidal Depression. That is, short-term life review led
      to higher hedonic tone scores, and long-term life review led to better mental
      health scores in healthy young adults. These results suggest that both short- and
      long-term life review in an interview promote young adults' immediate
      psychological well-being. Further research is required for young adults who have
      psychological problems.

PMID- 14650694
TI  - Effects of instructions and representation on mathematical problem-solving.
AB  - We investigated whether specific instructions have different representations for
      target problems, and hence whether task representations mostly affect the
      direction of typical errors in permutation problem-solving. We hypothesized that
      different instructions produce specific representations of a permutation problem
      in an identical description. The 39 participants were randomly assigned to the
      three groups: the equation instruction group, the subgoal instruction group, and
      the control group. Results confirmed our prediction that the treatment groups
      solved the problem more correctly than the control group. More importantly, a
      subgoal instruction (a set of steps in a meaningful task) decreased the typical
      mistakes. Educational implications are discussed.

PMID- 14650695
TI  - Aggressive and nonaggressive antisocial behavior in adolescence.
AB  - This study examined whether a distinction between aggressive and nonaggressive
      antisocial behavior can be empirically verified in a large (254 girls and 254
      boys) nonclinical (community) sample of Dutch adolescents between 12 and 18 years
      old. The results of confirmatory factor analysis for both boys and girls shows
      that aggressive and nonaggressive antisocial behaviors do not represent a single
      underlying dimension, but two separate constructs with moderate independence
      among them. These findings suggest that the conceptualization of adolescent
      antisocial behavior as a one-dimensional phenomenon is of questionable utility
      and supports growing evidence that aggressive antisocial behavior is distinct
      from other forms of antisocial behavior.

PMID- 14650696
TI  - Are parents' and children's thinking styles related?
AB  - This study extends the investigation of the validity of Sternberg's theory of
      mental self-government to mainland Chinese secondary school students and their
      parents. The assumption of a 'socialization effect' underlying the theory was
      subjected to broader investigation. 232 students and their parents responded to a
      range of demographic questions and to the Thinking Styles Inventory which is
      based on Sternberg's theory. The two major findings are that (1) Sternberg's
      theory is valid with both samples, and (2) students' thinking styles are related
      not only to their personal factors, e.g., sex, grade, and self-rated abilities,
      but also to their parents' thinking styles. These findings have implications for
      school teachers and counselors as well as for parents.

PMID- 14650697
TI  - Decision frame and procedural justice: interactive effects on perceptions of
      distributive justice.
AB  - This work examined the effect of procedural justice and item frame on responses
      to positively and negatively worded survey items. Under conditions of low
      procedural justice, there is a significant difference in the rating of
      distributive justice items positively and negatively framed, but not when
      procedural justice is high. Implications for decision frame theory and biasing of
      responses to survey items are considered.

PMID- 14650698
TI  - Generalization of the negativity effect to self-attributions.
AB  - In 1979 Reeder and Brewer reported that people make stronger attributions for
      negative behaviors than for positive ones, following Hastorf and Cantril's
      statement that people are motivated to maintain positive self-views. The present
      study tested whether 67 participants would make stronger self-attributions for
      negative behaviors than for positive ones by having them indicate the number of
      times that they had to engage in a specific behavior before it would become a
      trait they possess. Analysis confirmed that participants make stronger self
      attributions for negative behaviors than for positive behaviors.

PMID- 14650699
TI  - Attitudes toward physician-assisted suicide and death anxiety.
AB  - A scale to measure approval of physician-assisted suicide was devised. Scores on
      the scale were uncorrelated to death anxiety in a sample of 168 students.

PMID- 14650700
TI  - Relationship between human papilloma virus infection and abnormal Pap smear in
      HIV-seropositive women at Siriraj Hospital.
AB  - The purpose of this prospective study was to determine the prevalence of human
      papillomavirus and abnormal Pap smear in HIV-seropositive women, particularly in
      HIV-seropositive women who undertook antiretroviral drug. The consecutive series
      of 178 HIV-seropositive women was enrolled in the Department of Obstetrics and
      Gynecology, Siriraj Hospital. All general information and laboratory results of
      the patients were recorded. Pap smears are obtained from the endocervix, cervical
      transformation zone and vagina by using a cotton tip stick and Ayre spatula, as
      described in the VCE technique. The patients were assigned into two groups, the
      AZT and non-AZT group. The comparison between the groups was calculated
      statistically. It was found that 88 of 178 HIV-seropositive women (49.4%)
      undertook Zidovudine. The prevalence of abnormal Pap smear in HIV-seropositive
      women, who had an abnormal Pap smear, was 59.6 per cent. However, the prevalence
      of human papillomavirus infection detected by Pap smear was reported in 17
      patients (9.6%). There was no difference between the AZT and non-AZT group
      statistically. There was a significantly higher probability of finding an
      abnormal Pap smear for cervical dysplasia in HIV-seropositive women who were
      infected with human papillomavirus compared to. It is concluded that there is a
      higher risk of developing cervical dysplasia in HIV-seropositive women who carry
      the human papillomavirus.

PMID- 14650701
TI  - Efficacy and safety of rilmenidine, a selective imidazoline I1 receptor binding
      ligand, in mild-to-moderate Thai hypertensive patients.
AB  - BACKGROUND: Rilmenidine is an antihypertensive agent that selectively binds to
      imidazoline I1 receptor located in the brainstem and kidney. It acts both
      centrally by reducing sympathetic overactivity and in the kidney by decreasing
      water and sodium overload. This dual action leads to the immediate and delayed
      control of blood pressure caused by this drug. OBJECTIVE: The aim of this study
      was to assess the efficacy and safety of rilmenidine as monotherapy in mild-to
      moderate essential hypertensive patients. METHOD: An 8-week, open-labeled,
      multicenter study was conducted in Thai patients with mild-to-moderate essential
      hypertension. Rilmenidine 1 mg/day was given for 8 weeks. The dose could be
      titrated up to 2 mg/day according to the patient's blood pressure response at
      week 4. The primary efficacy parameters were the mean reductions in systolic and
      diastolic blood pressure. The proportions of patients whose blood pressure
      normalized or responded were evaluated as secondary efficacy parameters. Safety
      parameters were assessed by the changes in heart rate and reported side effects
      during the treatment period. RESULTS: 103 subjects (44.7% men) with a mean age of
      53 +/- 9.7 years completed the 8-week follow-up. At baseline, 46.6 per cent and
      53.4 per cent of the patients were classified with mild and moderate
      hypertension, respectively. The mean blood pressure was 154/93 mmHg. After the 8
      week treatment, there was a significant decrease in blood pressure to 140/86 mmHg
      (p < 0.001), with mean pressure reduction of 14/7.5 mmHg. The normalization rate
      was 44 per cent and the response rate was 68 per cent. No significant changes
      were found for mean heart rate and any laboratory parameters tested. Only 17
      patients reported mild and transient side effects such as drowsiness and dryness
      of the mouth and throat, which required no treatment. CONCLUSION: This study has
      shown that rilmenidine is an effective and well tolerated monotherapy in Thai
      patients with mild-to-moderate essential hypertension.

PMID- 14650702
TI  - Transcatheter closure of perimembranous ventricular septal defect with immediate
      follow-up.
AB  - BACKGROUND: Surgical closure of membranous ventricular septal defect (VSD) is
      performed by open heart surgery with a small but significant morbidity and
      mortality. The authors reported here the first group of patients who underwent
      transcatheter closure of membranous VSD. METHOD: Patients who had membranous VSD
      with significant left to right shunt as shown by echocardiogram were selected for
      closure. A standard right and left heart catheterization was done under general
      anesthesia. A complete arteriovenous wire loop from the aorta to the left
      ventricle and VSD out into right ventricle was formed in order to guide the
      delivery sheath into the VSD from the right ventricle. The authors used the new
      Amplatzer Membranous VSD Occluder (AGA Medical Corp., USA) to deploy in the VSD
      position. RESULTS: There were 4 patients in the present study with age range of 2
      to 24 years old (median: 4 years old). Their weight ranged from 10 to 45 kg
      (median: 12 kg). Qp:Qs ranged from 1.7-2.5 to 1. The device diameter selected was
      from 6 to 10 mm. All of them were placed without any residual shunt. At one month
      follow-up all the patients had echocardiographic examination which showed no
      evidence of residual shunt. CONCLUSIONS: The authors demonstrated that
      transcatheter closure of membranous VSD could be safely and effectively performed
      in small children. This device also provided an opportunity for closure of VSD in
      patients with pulmonary hypertension.

PMID- 14650703
TI  - Clinical features of corrosive ingestion.
AB  - OBJECTIVE: To study the clinical presentation after corrosive ingestion. SETTING:
      A University Hospital. DESIGN: Prospective descriptive study. PATIENTS AND
      METHOD: Corrosive ingestion patients were studied, from July 2000 to December
      2002. Reasons for ingestion, symptoms, physical findings and routine
      investigations were recorded in a standard form. Data analysed using the
      descriptive statistical method. RESULTS: There were 73 patients, 55 women and 18
      men, median age 22 years, 48 (65.8%) of whom had ingested strong acid, 3 (4.1%)
      ingested strong alkali. Suicidal gesture was the most common reason for ingestion
      (89.2%). The amount of ingestion was less in accidental cases. Symptoms of
      nausea/vomiting, drooling and abdominal tenderness were associated with the
      amount of ingestion, while severity of lips, buccal mucosa and palate injuries
      was significantly related with strong corrosive agents (p < 0.05). Leucocytosis
      was found in patients who had symptoms of drooling, hoarseness, stridor and signs
      of mucosal slough or superficial ulcers (p < 0.05). Four required surgery. Two of
      them had esophago-gastrectomy. Twenty-one patients were followed-up, with the
      median follow-up time of 11 (1-28) months. One patient died from HIV infection.
      The rest were normal. CONCLUSION: Drooling and oral mucosal slough or ulcers were
      significant findings and were related to the amount and strength of the corrosive
      substance ingested, respectively. To meet the goal of a holistic approach,
      attention must also be given to psychiatric management, and surgeons should
      provide a supportive role.

PMID- 14650704
TI  - Prognostic factors associated with severe leptospirosis.
AB  - To determine the prognostic factors associated with severity and death of
      leptospirosis, the authors conducted a hospital based cross sectional study by
      collecting data of adult patients that were admitted to Phrae Hospital for
      leptospirosis from 1998 to 2001. The serology was confirmed with a microscopic
      agglutination test (MAT). The variables obtained from the history, examination,
      behavioral risks, investigations, and initial treatment especially the data of
      the first day of admission were examined for association with severity. Of 362
      patients, 214 were classed as nonsevere patients, 81 were severe with
      complications (serum creatinine > or = 3 mg/dl and/or patients with respiratory
      failure) and 67 died. Multivariate logistic regression demonstrated that five
      factors were independently associated with severity: hemoptysis, platelet count
      (Plt) < 100,000/mm3, total bilirubin > 2.5 mg/dl, white blood cell count >
      13,000/mm3 and hematocrit (Hct) < 30 per cent. Five factors associated with
      mortality are: respiratory failure (or respiratory rate; RR > 24/min),
      hemoptysis, oliguria, metabolic acidosis (or bicarbonate < 20 mmol/l) and
      thrombocytopenia (or Plt < 100,000/mm3). Identification of these factors might
      provide useful selection criteria for patients who need early admission or
      transfer to the intensive care unit.

PMID- 14650705
TI  - Newborn screening for congenital hypothyroidism in Khon Kaen University Hospital,
      the first three years, a preliminary report.
AB  - Between January 2000 and December 2002, 9,558 of 10,868 live births at
      Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, were screened
      for congenital hypothyroidism (CH). Dried blood spot thyroid stimulating hormone
      (TSH) was collected at age 48 hours or older. The cut-off TSH level for recall
      test was > 25 mu/L. Serum thyroxine (T4), Free T4 and TSH were performed during
      the confirmatory test. Six of 24 infants recalled for confirmatory thyroid
      function tests had abnormal tests. Primary CH was confirmed in 3 infants and
      thyroxine treatment was given. Two of the three infants had thyroid dysgenesis,
      one had normal thyroid gland. Three infants showed borderline CH from the
      confirmatory test, only one had borderline CH from the second confirmatory test
      and also received thyroxine treatment. Twenty infants with false positives during
      the screening and confirmatory tests were regularly followed-up for growth,
      development and thyroid function tests. The incidence of primary CH in this sole
      tertiary care government hospital in Northeast Thailand was 1:3,186. Routine
      newborn CH screening would ensure early detection and treatment.

PMID- 14650706
TI  - Nationwide survey of the health status and quality of life of elderly Thais
      attending clubs for the elderly.
AB  - Thailand is seen as a developing Southeast Asian country with a fast-growing
      number of senior citizens. Meanwhile, they are also encouraged to attend a local
      club for the elderly for the sake of health promotion and disease prevention.
      Knowledge of the quality of life as well as the health status of elderly people
      in this setting would be invaluable for further planning. 1811 individuals from
      66 provinces, who attended clubs for the elderly were recruited. Structured
      questionnaires with detailed instructions were distributed to clubs for the
      elderly nationwide. 61.4 per cent had a good quality of life. The independent
      factors determining poor quality of life were as follows: not living with a
      spouse, poor financial status, no regular exercise, sleeping or hearing
      difficulty, not taking milk regularly, suffering from joint pain or diabetes
      mellitus, history of a fall within the last 6 months and a poor mobility score
      and score of instrumental activities of daily living. No regular exercise had the
      highest adjusted odds ratio (2.38: 95% CI: 1.61-3.51). The main factors
      determining a poor quality of life in any region of the country were
      socioeconomic background in the northern region, having less exercise and joint
      pain in the eastern part and diabetes mellitus in the western region. CONCLUSION:
      All these factors should be part of the geriatric assessment among elderly Thais.
      Socioeconomic factors could be employed to screen for those who are at risk while
      the other reversible factors should be highlighted and treated properly in order
      to reduce the outcomes of poor quality of life in those attending clubs for the
      elderly.

PMID- 14650707
TI  - Relative bioavailability study of 20-mg enalapril tablets in healthy male
      volunteers.
AB  - The pharmacokinetic and relative bioavailability studies of 20-mg enalapril
      tablets, the test product manufactured by Biolab, Thailand compared to the
      reference product (Merck Sharp & Dohme, USA) was conducted in 14 healthy Thai
      male volunteers following a single dose, two-period, crossover design. Each
      subject received 20-mg enalapril tablets of both formulations with a 1-week
      washout period. Plasma samples collected over a 24-h period after administration
      were analyzed by LC/MS/MS. Pharmacokinetic parameters were determined by using
      non-compartmental analysis. Regarding bioequivalence testing, the 90 per cent
      confidence intervals of Cmax and AUC(0-infinity) ratios (test/reference) of
      enalapril were 101.8-134.9 per cent and 105.9-121.4 per cent and those of
      enalaprilat were 104.2-122.3 per cent and 104.5-118.1 per cent. Based on the
      European bioequivalence guideline, the 90 per cent confidence intervals of Cmax
      and AUC(0-infinity) ratios of both parent and metabolite forms were within the
      acceptable ranges of 70-143 per cent and 80-125 per cent, respectively. It was
      concluded that the test formulation was bioequivalent to the reference
      formulation and both formulations can be used interchangeably in clinical
      practice.

PMID- 14650708
TI  - Drug-resistant tuberculosis among prisoners of three prisons in Bangkok and the
      vicinity.
AB  - The purpose of this study was to determine the prevalence of drug-resistant
      tuberculosis and some factors associated with drug resistance among prisoners of
      three prisons in Bangkok and the vicinity. Susceptibility testing to four first
      line antituberculous drugs was performed on 165 M. tuberculosis strains isolated
      from prisoners of three prisons including Klongprem Central (KC) prison,
      Bangkwang Central (BC) prison and the Correctional Institution (CI) for Male Drug
      Addicts. Of 165 smear positive tuberculosis (TB) cases with drugs susceptibility
      results, resistance to one or more drugs was 49.7 per cent. Resistance to one,
      two, three, and four drugs was 20.0, 13.3, 4.2 and 12.1 per cent, respectively.
      Multidrug resistant tuberculosis (MDR-TB) was 18.8 per cent. Patients classified
      as primary and acquired drug resistant were 6.7 and 50.0 per cent. The primary
      drug resistance to one or more drugs among prisoners at KC, BC and CI were 42.5,
      36.4 and 53.9 per cent, respectively and MDR-TB were 8.2, 3.0, and 7.7 per cent,
      respectively. Of several factors analyzed in the present study, only a history of
      previous TB treatment was significantly associated with drug resistance (p <
      0.05). In conclusion, the results indicate the high prevalence of drug-resistant
      tuberculosis and the seriousness of the TB problem in prisons. The public health
      sector and prison authorities should work in close collaboration and co
      ordination to continue improving TB case detection. Directly Observed Treatment
      Short course (DOTS) is highly recommended. Moreover, discharged prisoners with
      tuberculosis should be appropriately referred to hospitals or TB control centers.

PMID- 14650709
TI  - Uterine artery resistance index above 95 percentile: prevalence and adverse
      perinatal outcome prediction in pregnancies complicated by hypertensive
      disorders.
AB  - Uterine artery resistance index (UARI) was determined in a cohort of pregnant
      women complicated by a hypertensive disorder. The prevalence of the value above
      95 percentile (UARI95) and its prediction of adverse perinatal outcomes were
      evaluated. Fifty-eight women were included in the study. The prevalence of UARI95
      in this group of women was 27.6 per cent. The correlations between mean UARI95
      and adverse perinatal outcomes were: 31.6 per cent sensitivity, 74.4 per cent
      specificity, with only 60.3 per cent accuracy. The mean UARI95 does not qualify
      as a reliable screening test for adverse perinatal outcomes in pregnancies
      complicated by hypertensive disorders.

PMID- 14650710
TI  - Detection of Clostridium difficile toxin A and B genes from stool samples of Thai
      diarrheal patients by polymerase chain reaction technique.
AB  - The prevalence of Clostridium difficile isolated from stools of Thai adult
      patients with suspected antibiotic-associated diarrhea (AAD) was 18.64 per cent.
      The recovery rate of toxin genes (tcdA and tcdB) by polymerase chain reaction
      (PCR) from stool samples yielded almost the same compared to the recovery rate of
      the toxin detection by enzyme immunoassay (EIA), which were 44.9 per cent and
      46.7 per cent, respectively. Correlation of toxin gene detection by PCR and toxin
      detection by EIA was 90.6 per cent. All but one stool sample, the tcdA gene was
      detected together with the tcdB gene. Both genes were always detected together
      from tox gene-positive strains. Although, there were some discrepancy results for
      certain samples, the direct PCR-based-detection of C. difficile tox genes in
      stool samples seems to be the appropriate method for the diagnosis of C.
      difficile diarrhea. The PCR assay should be a recommended technique to be used
      routinely in laboratories. Further optimization of the technique to increase the
      sensitivity of the PCR assays is still needed. However, a quantitative isolation
      of the organism from stools of suspected antibiotic-associated diarrhea (AAD) or
      antibiotic-associated colitis (AAC) patients may give some evidence for
      clinicians in hospitals who cannot perform PCR-based or EIA-based techniques,
      since 48.6 per cent of the isolates were demonstrated as toxigenic strains.

PMID- 14650711
TI  - Thrombocytopenic purpura associated with miliary tuberculosis.
AB  - The authors report a case of thrombocytopenia associated with miliary
      tuberculosis. The patient was a 28-year-old woman who was admitted because of
      massive upper gastrointestinal hemorrhage and acute respiratory failure. Chest
      radiographs revealed diffuse bilateral reticulonodular infiltration and complete
      blood count was significant for severe thrombocytopenia. Bone marrow biopsy was
      performed to investigate the cause of thrombocytopenia and demonstrated multiple
      tiny caseating granulomas suggesting miliary tuberculosis (TB). She received anti
      TB therapy and a short course of steroid with good response. Platelet count
      returned to normal limit within 10 days. Although isolated thrombocytopenia is
      uncommon in TB, it is still important to consider TB in the differential
      diagnosis of thrombocytopenia, particularly in patients with abnormal chest
      radiographs. Bone marrow examination is very helpful in this situation.

PMID- 14650712
TI  - Intravitreal angiostrongyliasis: report of 2 cases.
AB  - Two male patients presented with unilateral blurred vision. A small motile worm
      was found in the vitreous cavity in both cases. In one case, another dead,
      disintegrated worm was noted in the inferior portion of the vitreous cavity. On
      each eye, vitreous surgery was performed and the worm was removed by an
      aspirator. Both worms were identified as Angiostrongylus cantonensis. Since both
      patients had no signs of meningitis, lumbar puncture was not done. Long-term
      follow-up confirmed the benefit and safety of the vitreous surgery. Fluorescein
      angiography revealed severe pigmentary alteration, probably from inflammation of
      the choroid and retina due to subretinal migration of the worm prior to access
      into the vitreous cavity.

PMID- 14650713
TI  - Parasitic leiomyoma: a case report of an unusual tumor and literature review.
AB  - Uterine leiomyomas are one of the most common tumors in women. Parasitic
      leiomyoma is an uncommon type of uterine leiomyoma. It may present with a wide
      spectrum of symptoms. The authors report a case of a 44-year-old woman who
      presented with a palpable pelvic mass and increased frequency of urination for 2
      years. A parasitic leiomyoma that had blood supplies from the common iliac
      vessels was diagnosed during the operation. Total abdominal hysterectomy and mass
      removal were performed without complication. Even though a parasitic leiomyoma is
      uncommon, it should be included in the differential diagnosis of pelvic mass. The
      management depends on the operative finding and the desired fertility function of
      the patients. Literature on parasitic leiomyoma is also reviewed.

PMID- 14650714
TI  - Ethics in general practice.

PMID- 14650715
TI  - Presenting new screening guidelines.

PMID- 14650716
TI  - There they go again.

PMID- 14650717
TI  - Sticking it to the kids.

PMID- 14650718
TI  - The empire strikes back.

PMID- 14650719
TI  - Patient, medicate thyself.

PMID- 14650720
TI  - Single payer or pluralism?

PMID- 14650721
TI  - The anomalous health status of Texas border counties.
AB  - The health status of Texas border counties is anomalous in that the combination
      of poor health care services, low socioeconomic status, and low education rate
      does not result in the expected increase in age-adjusted mortality rate and
      shortened life expectancy. The anomaly appears to be due largely to the
      combination of a high Hispanic population density in this region, specifically
      Mexican-Americans, and to the phenomenon of Hispanic longevity. The latter is
      considered to be based on a variety of possible cultural factors. In the face of
      continuing escalations in the cost of health care, further definition of what
      those factors are and how they could be incorporated into the delivery of health
      care in our state should be a priority for state health policy.

PMID- 14650722
TI  - Physicians' views and practice of smoking cessation.
AB  - To assess recent smoking cessation practices of physicians in East Texas and to
      determine whether physicians' practices meet current standards, a 43-item
      questionnaire was mailed in May 2000 to 1955 physicians in East Texas. The 406
      physicians who finished and returned the survey were included in this study. The
      questionnaire covered a wide range of sociodemographic variables, and physicians'
      attitudes and activities related to patients' smoking cessation. The survey
      results indicated that most physicians frequently ask their patients about
      smoking and advise patients who smoke to quit, but only half of all respondents
      always ask about their patients' smoking status and advise smokers to quit.
      Furthermore, less than half of surveyed physicians are willing to spend
      additional time to conduct additional activities that involve other office
      personnel or to provide additional smoking cessation assistance to help their
      patients quit.

PMID- 14650724
TI  - [Compulsory services].

PMID- 14650723
TI  - The prevalence of antibodies against B. burgdorferi, an indicator for Lyme
      borreliosis in dogs? A comparison of serological tests.
AB  - Five serological tests for the detection of IgM and IgG antibodies to Borrelia
      burgdorferi, the causative microorganism of Lyme borreliosis (LB), were compared
      in 1177 sera from Dutch dogs: 401 healthy working hunting dogs, 100 healthy city
      pet dogs, 629 city dogs suspected of having LB with various clinical symptoms,
      and 47 hunting dogs with intermittent lameness. The results of the in-house
      species-independent enzyme immunoassay (i.e. an EIA which can be used to test
      serum samples from different animal species) showed a strong agreement (kappa:
      0.78-0.81) with those of an experimental and a commercially available EIA
      (Genzyme Virotech, Russelsheim, Germany) for the detection of canine IgG
      antibodies to B. burgdorferi. Furthermore, the sensitivity of the in-house EIAs
      for the detection of antibodies to B. burgdorferi was independent of the
      antigenic heterogeneity, as demonstrated by the results of sera from dogs
      suspected of LB with various clinical symptoms: lameness (n = 60), and
      neurological (n = 60) and skin disorders (n = 52). Because of its high
      sensitivity for IgM antibodies, the indirect assay (Diagast, Pessac, France)
      proved to be an interesting tool for the detection of an acute Lyme infection in
      dogs. However, in this study a positive serological result could not be linked to
      any clinical symptom that has been related to LB in dogs. Results showed no
      difference in seroprevalence between dogs considered at high or at low risk of a
      B. burgdorferi infection. It was concluded that LB is an uncommon disease in the
      Dutch dog population despite the fact that many of Dutch dogs are infected with
      B. burgdorferi. Because of this low prevalence, the use of any immunoassay to
      support the clinical diagnosis of LB in dogs might be of limited value.
      Nevertheless, the species-independent EIA could be valuable in
      seroepidemiological studies when sera of several different animal species need to
      be tested.

PMID- 14650725
TI  - [VWA speaks to farmer, veterinarian and minister].

PMID- 14650726
TI  - [Waiting times for veterinary drugs in guidelines disappears].

PMID- 14650727
TI  - [DIB (Veterinarians in Business) visits colleague Niels van Elk in Dolfinarium
      Hardewijk, the Netherlands].

PMID- 14650728
TI  - [Veterinarians back in balance with Veterinary Society Meeting 2003].

PMID- 14650729
TI  - [Veterinarians have difficult social circumstances].

PMID- 14650730
TI  - [Workshop VVAA: the veterinarian financially and economically in balance. Net
      result does not increase with turnover profits of large animal practices].

PMID- 14650731
TI  - [Workshop 2--change management by Paul Nyst].

PMID- 14650732
TI  - [Ton de Ruijter elected again as chairman KNMvD].

PMID- 14650733
TI  - [Vision KNMvD about the 'Future intensive animal husbandry' to the minister of
      LNV].

PMID- 14650734
TI  - Undesirable reactions of domestic pigeons to vaccination against paramyxovirus
      type 1.
AB  - Subcutaneous vaccination of fancy and racing pigeons with inactivated oil-based
      vaccines protects against all clinical manifestations caused by the Paramyxovirus
      type 1. Correct application of the vaccine may occasionally result in the
      development of granulomas or abscess-like lesions on the site of vaccine
      application. Although protected against disease as proven by challenge
      experiments, a variable proportion of vaccinated pigeons do not react with the
      formation of detectable serum antibodies. The pathogenesis of granuloma and
      abscess-like lesion developments and the failure to form humoral antibodies are
      presently not understood. Questions relating to legal liability of vaccinating
      veterinarians are briefly discussed.

PMID- 14650735
TI  - [Comparison of the influence of different anesthetic protocols in the development
      of post-anesthetic arrhythmia in the dog].
AB  - Post-anesthetic holter monitoring was performed in 2 patient groups in order to
      compare the incidence of cardiac arrhythmias as a result of different anesthetic
      protocols. The 2 groups differed in their anesthetic protocol. Both groups
      received levomethadone as pre-anesthetic. The dogs in group A (n = 30)
      additionally received diazepam, the dogs in group B (n = 30) received propofol
      instead. Anesthesia was maintained by isoflurane in group A and a propofol
      constant rate infusion in group B. In each patient 2 holter monitorings were
      performed. The first recording began directly after anesthesia. As a comparison a
      second recording was performed on the 5th post-operative day. The recorded number
      of arrhythmias was low and no statistical difference was demonstrated between the
      2 patient groups.

PMID- 14650736
TI  - [Suckling behavior of llamas (Lama glama)].
AB  - In the present study the suckling behaviour of six Ilama crias was analysed. A
      total of 3398 suckling bouts were observed and evaluated. The crias mostly
      suckled in a reverse parallel position with no side preference. The cria
      initiated suckling in most suckling bouts whereas the dams usually ended them.
      The total number of suckling bouts could be divided into two types: suckling
      bouts of short duration and suckling bouts of long duration. There were no
      significant differences in duration per suckling bout among the different ages of
      crias. But the animals suckled less frequently and spent less total time suckling
      as they grow older. The age related differences and evidence for a dual function
      (nutrition, social contact) of suckling behaviour are discussed.

PMID- 14650737
TI  - [Population genetic analysis of the heritability of gutteral pouch tympany in
      Arabian purebred foals].
AB  - The objective of the present study was to analyse the importance of the
      influences of the sex, inbreeding coefficient and the additive genetic
      contribution to the occurrence of guttural pouch tympany in Arabian foals. Horses
      affected by guttural pouch tympany were ascertained in the Clinic for Horses,
      School of Veterinary Medicine Hannover. The data comprised 27 Arabian purebred
      foals with guttural pouch tympany. Of these 27 animals 22 were patients of the
      Clinic for Horses between 1994 and 2001 and 5 Arabian foals were sampled on the
      studs. Information on the pedigrees of these patients allowed us to sort in the
      affected foals into four families with a total of 276 animals. Female foals were
      more often affected by guttural pouch tympany. The difference was 11.9% in favour
      of female foals. The size of the inbreeding coefficient was not important for the
      occurrence of guttural pouch tympany. The heritability estimate for the frequency
      of guttural pouch tympany using a threshold model was 0.49 +/- 0.28. This is the
      first report that could show a genetic component responsible for guttural pouch
      tympany in foals.

PMID- 14650738
TI  - Comparative efficacy of flubendazole chewable tablets and a tablet combination of
      febantel, pyrantel embonate and praziquantel against Trichuris vulpis in
      experimentally infected dogs.
AB  - Fourteen of 23 dogs developing patent Trichuris vulpis infections by 120 days
      p.i. with 5000 embryonated eggs were allocated into three groups. One group was
      treated with flubendazole 220 mg chewable tablets (Flubenol) at the recommended
      dose regimen once daily for 3 days. The second group was given the recommended
      single treatment with a tablet containing 150 mg febantel, 144 mg pyrantel
      embonate and 50 mg praziquantel in combination (Drontal Plus). The third group
      remained untreated. All dogs were necropsied for worm counts 10 or 11 days after
      (first) treatment. No worms were recovered from the flubendazole treated dogs
      resulting in a significant worm count reduction of 100%. In contrast, 2 of 5
      animals treated with the combination of febantel, pyrantel embonate and
      praziquantel remained infected; the geometric mean worm burden was reduced by
      99.4% as compared to the control group but did not differ significantly from
      those of the controls.

PMID- 14650739
TI  - Epidemiological study on clinical bovine dermatophilosis in northern Ethiopia.
AB  - A total of 5586 indigenous and cross breed cattle were examined for clinical
      dermatophilosis, and 292 (5.22%) were positive. In indigenous cattle,
      statistically discernible (p < 0.05) difference was recorded between the
      prevalence in wet (5.5%) and dry (4.0%) seasons. During both seasons, infestation
      with A. Variegatum significantly (p < 0.05, chi 2 = 59.9) influenced clinical
      dermatophilosis. A. variegatum-infested cattle were at 7x higher risk (OR, Odds
      Ratio = 6.8) of acquiring the disease than non-infested ones. Logistic regression
      analysis of the overall prevalence showed a significant difference (p < 0.05)
      between prevalence in indigenous and cross breeds; the crossbreeds being at about
      3x higher risk (OR = 2.68). Improved management reduced the prevalence in cross
      breeds from 15.1% in dry to 8.6% in wet season suggesting the significance of
      management in the epidemiology of dermatophilosis. The disease occurrence was
      also significantly (p < 0.05, chi 2 = 133.05) affected by agro-climatic
      (altitude) variation suggesting the impact of rainfall, humidity, vegetation and
      vector population that varied with altitude. Age and gender had no influence (p >
      0.05) on the disease. Our result showed that season of the year, breed,
      management, infestation with A. variegatum and agro climatic difference are
      important risk factors influencing the disease pattern in the region. A tick
      control strategy and a better and adequate management particularly when keeping
      cross breeds are recommended.

PMID- 14650740
TI  - [Case report: Porcine circovirus type 2 infection in an European wild boar (Sus
      scrofa) in the state of Brandenburg, Germany].
AB  - This case represents the first case of Porcine Circovirus Type 2 (PCV-2)-
      infection in a free living European wild boar associated with morphological
      lesions, which are regarded as characteristic for Postweaning Multisystemic
      Wasting Syndrome (PMWS) in domestic pigs. The animal, an approximately 10 month
      old male, was found dead in a rural area within the state of Brandenburg,
      Germany. The closest commercial pig farm is located in 3 km distance from the
      spot where the carcass was found. At necropsy, the animal was found to be in a
      runted condition. Morphological investigation revealed two lesion complexes.
      Firstly, lymphatic depletion was present in different organs. Mainly the white
      pulp of the spleen was affected, where lymph follicles and periarteriolar
      lymphatic sheaths were nearly completely depleted of lymphoid cells. The former
      lymphatic areas could only be identified by the presence of histiocytic cells.
      Secondly, there were widely distributed lesions indicative of a bacterial
      septicemia i.e. purulent-necrotizing lymphadenitis, pulpous hyperplasia of the
      spleen, miliary lytic liver necroses and foci of fibrinous pneumonia. Within the
      lesions, bacterial colonies were found (short Gram-negative rods). Bacteriology
      revealed a septicemic Salmonella choleraesuis var. Kunzendorf--infection.
      Virologically, the animal was tested with negative results for Classical Swine
      Fever Virus and PRRSV. The unusual depletion of the lymphatic tissue mainly in
      the spleen led to the suspicion of a PCV-2 infection. Typical circoviral
      particles were found by negative-contrast electron microscopy in samples from
      spleen and lymph nodes. Using a commercial antiserum against Porcine Circovirus,
      positive staining was found by fluorescence microscopy in tonsils, spleen and
      lymph nodes. Finally, the virus was identified to be PCV-2 by species-specific
      PCR. The presented case rises the questions if PCV-2 is endemic in the European
      wild boar population at least in certain areas, if it is of pathogenetic
      importance for wild boars and if the virus present in wild boars is identical to
      that present in domestic pigs with PMWS.

PMID- 14650741
TI  - [Continuing education on swine diseases within the framework of the 225-year
      celebration of the Veterinary College of Hannover].

PMID- 14650742
TI  - [End stage renal failure is a chronic inflammatory disease].
AB  - For the past ten years, the discovery of the Toll-like receptor family have
      greatly contributed to our current understanding of the innate immune system. The
      first part of this article draws up the inflammatory reaction by integrating
      these new data. The second part deals with inflammation during end stage renal
      disease and introduces this special edition of Nephrologie: "Inflammation in
      dialysis, a daily concern". Through this edition, we would like to convince you
      that end stage renal failure is a chronic inflammatory disease and that better
      understanding of causes and consequences implied in dialysed patients
      inflammation will enable to improve their global therapeutic care.

PMID- 14650743
TI  - [Is C-reactive protein a marker of inflammation?].
AB  - C-reactive protein (CRP) is the prototype of acute-phase protein which is
      secreted by the liver in response to a variety of inflammatory cytokines. Levels
      of CRP can increase up to 1000-fold very rapidly after the onset of inflammation
      and decrease just as rapidly with the resolution of aggression. CRP is a member
      of the ancient highly conserved pentraxin family of proteins and it is arranged
      in a cyclic homopentameric structure. The important role of CRP in innate
      immunity is largely due to its opsonizing abilities, its capability to activate
      human complement and to bind to immunoglobulin G receptors. CRP can bind
      phosphocholine largely present in bacterial membranes, cell membrane and
      lipoproteins, in addition CRP can recognize nuclear constituent in damaged cells.
      CRP can activate C3 convertase through the classical pathway but not C5
      convertase resulting in generation of opsonic complement fragments. Interactions
      of CRP with Fc receptors lead to the generation of proinflammatory cytokines and
      reactive oxygen species by monocyte/macrophage while inhibit neutrophiles
      functions. Recently, CRP was demonstrated to play an active role in atherogenesis
      and it has been largely proven that a microinflammatory state as defined by a
      moderate increase in CRP (up to 3 mg/l), is associated with an increased risk for
      arterial disease. Moreover it has been postulated that CRP may be a useful tool
      for monitoring drug therapy.

PMID- 14650744
TI  - [Inflammatory markers in dialysis: epidemiological data].
AB  - Inflammatory markers such as C-reactive protein are frequently elevated in
      patients treated by dialysis. Serum concentration of these markers are much
      higher than in the general population, in which it has been clearly shown that
      chronic inflammation is associated to the occurrence of cardiovascular events.
      The mechanisms leading to chronic inflammation in dialysis patients may be
      related to chronic inflammation per se, or to dialysis. Furthermore, in these
      patients, raised inflammatory markers are associated to malnutrition and
      increased cardiovascular morbidity and mortality. The association of
      inflammation, malnutrition and atherosclerosis defines the so-called MIA
      syndrome.

PMID- 14650745
TI  - [Inflammation markers in daily practice].
AB  - Cardiovascular diseases and infections remain the first mortality causes in ESRD
      patients. European recommendations for good clinical practice in the hemodialysis
      field advocate to use the inflammation markers in daily practice. These markers
      foretell both cardiovascular and global mortality. They also enable to detect the
      silent infections (parodontitis, Heliobacter pilory infection, shunt infection in
      PTFE), to make sure of the dialysis biocompatibility (microbiological quality of
      the dialysate, use of biocompatible membrane). The C-reactive protein is the most
      current and used marker. Its use, combined with the procalcitonin measurement,
      specific marker for bacterial infection, would enable the diagnostic and
      therapeutic strategy improvement.

PMID- 14650746
TI  - [Vascular access, an underestimated source of inflammation in dialysis patients].
AB  - The surveillance of inflammation in dialysis patient, by means of sensitive
      markers such as CRP, is strongly recommended in a continuous quality improvement
      treatment approach. Chronic inflammation being deleterious via several pathways
      including malnutrition, accelerated arteriosclerosis and beta 2M-amyloidosis,
      microinflammation must diagnosed and corrected as soon as possible in dialysis
      patients. Vascular access represents an underestimated source of inflammation in
      hemodialysis patients. In the absence of organic cause of inflammation, the
      vascular access should be always incriminated and meticulously investigated.
      Withdrawing the suspected prosthetic or unused material (PTFE or catheter) should
      be considered as the best way of correcting the inflammation and restoring the
      recombinant erythropoietin (EPO) activity in the dialysis patient.

PMID- 14650747
TI  - [Membrane biocompatibility in dialysis: the role of absorption].
AB  - Membrane biocompatibility is a concept that have gained clinical relevance. How
      to define a "biocompatible membrane" in hemodialysis is still object of
      discussion. Intermediate biochemical reactions, measured in the blood are more
      relevant than clinical events to document membrane's quality. In the absence of
      prospective studies, it is not possible to document that the constant use of a
      dialysis membrane governs risk of death in the hemodialyzed patient.
      Nevertheless, some clinical criteria are relevant, such as hemocompatibility,
      i.e. clotting of the extracorporeal circuit and heparin consumption,
      hypersensitivity reactions, denutrition associated with the "microinflammatory"
      stress induced by the hemodialysis session, occurrence of beta 2 microglobulin
      derived amyloidosis. Synthetic membranes are credited of higher biocompatibility
      than cellulosic membranes. In general, they are highly permeable to peptides and
      proteins of the middle molecular range that contain some uremic toxins. In
      addition to be "highly permeable", allowing convective transfert, some synthetic
      membranes (polymethylmetacrylate, polyacrylonitrile, polyamide) bind proteins.
      Protein adsorption into synthetic membrane results from electrical charges
      distribution both at the surface and in the bulk of the membrane. Ionic
      interactions are the main contribution to protein adsorption, but rheological
      conditions, surface rugosity, and porosity or gel consistency play also a role.
      Consequently, some membranes can bind cytokines and oxygen species, other bind
      endotoxins. Recently, it has been demonstrated that heparin coating was possible
      with the AN69-ST membrane, resulting in improved hemocompatibility and
      significant lessening of heparin requirements during the sessions. It appears
      that adsorption characteristics govern biocompatibility. For clinical practice, a
      classification of various membranes according to these properties must be taken
      into account.

PMID- 14650748
TI  - [Inflammation in peritoneal dialysis].
AB  - In patients on peritoneal dialysis, peritoneal membrane alterations with
      inadequate peritoneal membrane function may be induced during long-term therapy.
      Chronic inflammation triggers malnutrition and atherosclerotic cardiovascular
      disease contributing to high mortality. The role of catheter, peritonitis and
      peritoneal dialysis fluids is argued. A neutral pH, a lesser presence of glucose
      degradation products generated during heat sterilization and accelerating the
      production of advanced glycosylation end-products (AGEs) could be reduced with
      better biocompatibility of peritoneal dialysis fluids.

PMID- 14650749
TI  - [Uremic toxins].
AB  - Uremic toxins are compounds which exert biological action and which are retained
      in the body of patients with renal failure, whereas they normally should be
      excreted by the healthy kidneys into the urine. Only few retention solutes
      conform with the strict definition of uremic toxins. Uremic solutes can be
      subdivided into small water soluble compounds, small protein bound compounds and
      middle molecules. Most small water soluble compounds are not very toxic and the
      toxic ones often show a kinetic behavior that is different from that of urea. The
      uremic solutes that play a role in inflammation and cardio-vascular complications
      most often are middle molecules and/or protein bound. Hence, once more, the
      current marker urea is not representative for their mechanistic behavior.

PMID- 14650750
TI  - [Oxidative stress in chronic renal failure and hemodialysis].
AB  - Evidence has accumulated that oxidative stress resulting from the increased
      generation of oxidants (reactive oxygen species and chlorinated oxidants) by
      activated phagocytes at the contact of dialysis membranes and dialysate
      endotoxins and from the uremia-related profound deficiency in antioxidants
      (glutathion system mainly) plays a prominent role in the pathogenesis of the
      accelerated atherosclerosis process which accounts for almost one half of deaths
      in dialysis patients. However more recent studies of large cohorts of uremic
      patients have shown that oxidative stress is already present at an early stage of
      chronic renal failure, increases with the progression of uremia and that
      phagocytic cells are elective targets of uremic toxins. Our recent studies aimed
      at better characterizing oxidative stress in dialysis patients have led to
      describe the presence in the plasma of uremic patients of AOPP (Advanced
      Oxidation Protein Products) which proved to be potential uremic toxins and
      mediators of inflammation. A better knowledge of the respective contribution of
      bioincompatibility and uremic toxins at the origin of phagocyte activation will
      allow to develop therapeutic strategies aimed at reducing the incidence of
      oxidative stress related complications and with AOPP as a gauge of their
      efficacy.

PMID- 14650751
TI  - [Metabolic consequences of inflammation in kidney failure].
AB  - Chronic inflammation is very common in patients on maintenance dialysis. It is
      associated with an increase of many cytokines (especially: IL-1, IL-6 and TNF
      alpha). This inflammation leads to hormonal dysregulation (leptin, adiponectin,
      insulin). Increase in cytokines is associated with a high cardio-vascular morbi
      mortality for general population as well as for uremic patients. Many metabolic
      abnormalities are due to chronic inflammation: protein catabolism, anorexia and
      many others. Among them, the "metabolic" syndrome includes adiposis, dyslipemia,
      insulinoresistance and high blood pressure very often present in chronic uremic
      patients. It is still unknown whether anti-inflammatory treatments would improve
      inflammation consequences in dialysis.

PMID- 14650752
TI  - [Prevention of malnutrition in peritoneal dialysis patients].
AB  - Malnutrition is a frequent and serious problem for patients treated by peritoneal
      dialysis. Patients' survival depends on their nutritional status at the
      initiation of the dialysis treatment. Main malnutrition factors are inflammation,
      insufficient dialysis dose, peritoneal glucidic absorption and protein loss
      within the dialysate. These patients show a relationship between malnutrition,
      inflammation and cardiovascular diseases. To prevent malnutrition, it is
      necessary to reduce inflammation by improving dialysis solutions'
      biocompatibility and optimising the sodium regulation. The peritoneal membrane
      exposure to both glucose and its degradation products must also be reduced. In
      order to restrict protein losses, especially when peritoneal hyper permeability
      occurred, dialysis solutions containing amino acids can be used. Early dialysis
      treatment and a progressive increase of the dialysis dose corresponding to the
      decrease of the residual renal function can also be recommended.

PMID- 14650753
TI  - [Pain in kidney disease].
AB  - There are little data concerning the prevalence of pain and its intensity in the
      population suffering from kidney diseases. However, according to number of
      pathologies with a kidney impact, the sequellae of the kidney disease itself and
      the technology in this area, there is a risk for a high prevalence rate of either
      acute and/or chronic pain. This can be responsible for some degree of psychologic
      disturbances as a major impact on the quality of life. Pain management must be a
      challenge in this field as it may interfere with the kidney disease.

PMID- 14650754
TI  - [Recent data on the physiology of pain].
AB  - Along the time, the relation between a painful stimulus and the created
      perception keeps on evolving. The distortion between stimulation and perception
      concerns all the steps of the painful messages transmission, from the peripheral
      level to the supraspinal sites. At the peripheral level, C or A delta fibres are
      excited by noxious stimuli. Involved molecules are released from cellular lysis,
      inflamed surrounding tissues and C or A delta fibres themselves. The progresses
      of molecular biology have once again enriched this peripheral inflammatory mix,
      which composition becomes more and more complicated: ATP and P2X3 purinergic
      receptor, bradykinin and B2 bradykinin receptor, H+ and ASIC proton receptor,
      vanilloid receptor activated by heat, inflammation and increase in synthesis of
      sodic channels resistant to the tetradotoxine (TTXr).... The first synapses are
      modulated by excitatory amino-acids and many peptides, at the end of the
      peripheral nerves in the dorsal horn of the spinal cord A lot of supraspinal
      sites are activated: the brain stem, the pontomesencephalic regions, the thalamic
      sites and the cortex. Along the way, multiple mechanisms modulate the pain
      transmission: the painful perception depends on the balance between both exciting
      and inhibitory effects. Descending inhibitory controls triggered by noxious
      stimuli would play a decisive role in the extraction of the painful
      characteristic of information and would give it priority over other stimuli.

PMID- 14650755
TI  - [Inflammation and atherosclerosis].
AB  - Atherosclerosis is a vascular pathology in which inflammation plays a major role
      at every stage of the disease. The inflammatory process develops in response to
      abnormal cholesterol deposits in the intima of large arteries. The inflammatory
      reaction is initiated by a phase of endothelial activation induced by cytokines,
      oxidized low density lipoprotein (LDL) and/or changes in endothelial shear
      stress. This leads to the primary expression of endothelial adhesion molecules
      and chemokines followed by the recruitment and activation of circulating
      monocytes and lymphocytes. The clinical manifestations of atherosclerosis,
      including acute coronary syndromes, are the consequences of atherosclerotic
      plaque rupture/erosion that triggers thrombus formation leading to the occlusion
      of the vessel lumen. The local inflammatory process at the level of the
      atherosclerotic plaque might influence the stability of the plaque through its
      potential effects on the extracellular matrix, and on the plaque thrombogenicity.
      In humans, systemic inflammation has been recognized as a major risk factor of
      occurrence of acute coronary syndromes.

PMID- 14650757
TI  - Medical education--then and now.

PMID- 14650758
TI  - What INR is right for your patient?

PMID- 14650756
TI  - [Management of micro-inflammation in uremia].
AB  - Chronic micro-inflammation is commonly observed in patients with chronic renal
      failure. However, the causes of this micro-inflammation remain mainly
      indeterminated. Therefore, the appropriate therapeutic management of uremic
      microinflammation is not yet established. Meanwhile, it appears to be reasonable
      to use current non-specific anti-inflammatory therapies (e.g. ACEI, statins) in
      order to reduce uremic micro-inflammation. However, it is clear that such an
      approach is not sufficient, and further strategies (e.g. vitamin E) are warranted
      to optimize uremic micro-inflammation prevention.

PMID- 14650759
TI  - Keeping medicine strong.

PMID- 14650760
TI  - Early onset polycystic kidney disease: how early is early?
AB  - We report a case of a six-month-old infant with autosomal dominant polycystic
      kidney disease. He was a full term baby with an uneventful pre and postnatal
      period. He was delivered by uncomplicated vaginal delivery without forceps or
      fetal distress. His father was recently diagnosed with adult onset autosomal
      dominant polycystic kidney disease (APKD) with creatinine clearance around 25%
      30%. The parents requested renal ultrasound of the baby to screen for APKD. It
      revealed normal sized and normal shaped kidneys, but with multiple bilateral
      cysts in the renal cortices, each measuring about 5 mm-7 mm in diameter.
      Subsequent DNA analysis showed presence of PKD1 gene, present on chromosome 16.
      His renal function was within normal range. The baby needs to be regularly
      followed-up for the most common complications of APKD, including hypertension and
      renal insufficiency.

PMID- 14650761
TI  - Pink slip introduction.

PMID- 14650762
TI  - Cardiovascular genetics: case studies.

PMID- 14650763
TI  - Can employers put genetic information to good use?

PMID- 14650764
TI  - Is there a pink slip in your genes?

PMID- 14650765
TI  - Genetic testing and employment litigation.

PMID- 14650766
TI  - Constitutional classifications and the "gay gene".

PMID- 14650767
TI  - Genomic medicine: the human genome project from a healthcare provider's
      perspective.

PMID- 14650768
TI  - Genetic discrimination: does it exist, and what are its implications?

PMID- 14650769
TI  - Legislation and genetic discrimination.

PMID- 14650770
TI  - Reasons to eschew federal lawmaking and embrace common law approaches to genetic
      discrimination.

PMID- 14650771
TI  - Genetic testing and employment litigation.

PMID- 14650772
TI  - Application of administrative law to health care reform: the real politik of
      Crossing the quality chasm.

PMID- 14650773
TI  - Routine patient care in clinical trials: whose cost is it anyway?

PMID- 14650774
TI  - The misperception and misapplication of the First Amendment in the American
      pluralistic system: mergers between Catholic and non-Catholic healthcare systems.

PMID- 14650776
TI  - Red tape, burnout and fatigue.

PMID- 14650775
TI  - The Affordable Prescription Drugs Act: a solution for today's high prescription
      drug prices.

PMID- 14650777
TI  - Evidence in medical practice.

PMID- 14650778
TI  - Tiredness in general practice.

PMID- 14650779
TI  - Toxicity in head lice treatment.

PMID- 14650780
TI  - Fatigue--a general diagnostic approach.
AB  - BACKGROUND: Fatigue or excessive tiredness of body or mind is a common presenting
      problem in general practice. OBJECTIVE: This article provides a diagnostic model
      for the diagnosis of fatique in general practice. DISCUSSION: Fatigue is not a
      diagnosis but rather a symptom. Fatigue is interchangeable with terms such as
      tiredness, weariness, loss of energy, listlessness and exhaustion. It can be a
      difficult and frustrating symptom for the general practitioner to evaluate.

PMID- 14650781
TI  - Psychological and psychiatric causes of fatigue. Assessment and management.
AB  - BACKGROUND: Fatigue is a common presentation in general practice and its
      diagnosis and management can be a source of frustration to both doctor and
      patient. Although it may exist independently of other diagnoses, and in
      conjunction with physical disorders, fatigue is strongly associated with
      psychological disorders. OBJECTIVE: We propose an approach to the diagnosis and
      management of the psychological and psychiatric causes of fatigue, and present
      two clinical cases to highlight some of the discriminating features. DISCUSSION:
      Psychological causes should be considered in all patients with fatigue. Awareness
      of the range of causes of fatigue, experience in using readily available
      screening tests to detect psychological disorders, and knowledge of the
      recommended management regimens will facilitate the delivery of quality care to
      patients and the reduction of the morbidity associated with the underlying
      conditions.

PMID- 14650782
TI  - Chronic fatigue syndrome. The patient centred clinical method--a guide for the
      perplexed.
AB  - BACKGROUND: Chronic fatigue states are common in general practice and over the
      past 20 years there has been considerable worldwide consensus developed on the
      criteria for chronic fatigue syndrome (CFS) also commonly known as myalgic
      encephalomyelitis (ME). Chronic fatigue syndrome is an illness characterised by
      the new onset of disabling fatigue, accompanied by cognitive, musculoskeletal and
      sleep symptoms. There are no specific diagnostic tests or biological markers and
      the diagnosis is made by ruling out other causes of fatigue. The pathophysiology
      of CFS is still unclear. OBJECTIVE: This article discusses the application of the
      patient centred clinical method to the diagnosis and treatment of CFS.
      DISCUSSION: There is no new breakthrough in the diagnosis or management of CFS in
      spite of much research and controversy. There is considerable evidence that the
      best place to manage CFS is in primary care under the care of the patient's own
      general practitioner, but it has been suggested that doctors feel unable to deal
      with the problem. The patient centred clinical method offers a constructive guide
      to management. The author considers that the best hope for sufferers is self
      management guided by a supportive and helpful health professional, preferably the
      patient's own GP.

PMID- 14650783
TI  - Diagnostic and management strategies for anaemia in adults.
AB  - BACKGROUND: Anaemia is often an incidental finding or is discovered when patients
      present with nonspecific symptoms such as tiredness. OBJECTIVE: This article
      presents strategies to identify the cause of anaemia and uses four case studies
      to illustrate these principles. DISCUSSION: Few diagnostic tests can completely
      rule in or rule out causes of anaemia. This makes the investigation of anaemia
      complex. An understanding of the limitations of tests in aiding diagnosis is
      required.

PMID- 14650784
TI  - Fatigue and endocrine disorders. Causes and comorbidities.
AB  - BACKGROUND: Most causes of fatigue are ill defined, self limiting or elude
      diagnosis. Many endocrine disorders present with nonspecific features including
      fatigue, so are difficult to differentiate on clinical grounds. However, avoiding
      diagnostic delay is vital to prevent significant morbidity and mortality. Thus, a
      high index of suspicion and knowledge of appropriate investigations is important.
      Endocrine disorders predispose the individual to developing related disorders;
      fatigue may be one sign of associated comorbidity. OBJECTIVE: This article
      discusses the endocrine disorders that commonly present with or develop fatigue
      as a prominent feature, with emphasis on particular challenges for diagnosis,
      investigation or management. Screening recommendations for comorbid disease was
      generated by an extensive review of current evidence. DISCUSSION: The
      identification of endocrine disorders can be both challenging--due to patterns of
      presentation--and rewarding for doctors and patients alike, due to importance and
      effectiveness of treatment.

PMID- 14650785
TI  - Monitoring in high level care.
AB  - BACKGROUND: Prescribing for elderly patients in nursing homes in an area where
      appropriate patient monitoring is poorly managed. OBJECTIVE: This article
      discusses the use of some commonly prescribed medications in elderly nursing home
      residents and how these medications should be monitored. DISCUSSION: Many of the
      medications prescribed to nursing home residents may be appropriately prescribed
      initially, but their continuing prescription may be inappropriate in the setting
      of lack of effect and adverse reactions. It is important to appreciate that the
      response rate to many of the commonly prescribed medications such as tricyclic
      antidepressants, selective serotonin reuptake inhibitors, anticholinergics and
      antipsychotics, is limited in this population of patients and that they also have
      quite a significant potential for toxicity. Therefore, monitoring for the effects
      of therapy, as well as any potential adverse effects, is important to ensure the
      ongoing appropriateness of such prescriptions.

PMID- 14650786
TI  - Cognitive behavioural strategies for general practice.

PMID- 14650787
TI  - Adolescent health--as easy as EPC.
AB  - BACKGROUND: There are a number of very serious health trends for adolescent
      Australians. A major barrier to young people's access to high quality health care
      is poor general practitioner remuneration for longer consultations for complex
      adolescent issues. OBJECTIVE: This article discusses the use of the Enhanced
      Primary Care Medicare items for adolescents presenting to community general
      practice, youth specific health centres and community health centres. DISCUSSION:
      Medicare items for care planning, case conferencing, mental health, asthma,
      diabetes, and cervical screening may be used to improve outcomes for young people
      and increase GP remuneration in this poorly funded area.

PMID- 14650788
TI  - Dealing with subpoenas.

PMID- 14650789
TI  - The trouble with testing: screening.

PMID- 14650790
TI  - The art of treating Parkinson disease in the older patient.
AB  - BACKGROUND: Parkinson disease (PD) is a neurodegenerative disorder that increases
      sharply after the sixth decade. There are many disorders in the elderly that
      exhibit some parkinsonian signs that can be confused with PD. OBJECTIVE: This
      article discusses the diagnostic and management issues of PD in the elderly
      patient. DISCUSSION: Levo-dopa (L-dopa) therapy is the cornerstone of treatment
      for PD in the elderly. After 5-8 years of treatment, monitor complications such
      as fluctuations and dyskinesia usually occur and adjunct therapy may be required.
      Dopamine agonists can be used to smooth out motor fluctuations and amantadine is
      sometimes useful for dyskinesia. However, the adverse drug effects of adjunct
      therapy in the elderly are more common than with L-dopa alone, and risks need to
      be weighed up against benefits. Nonmotor complications including dementia,
      psychosis, depression, autonomic dysfunction and somnolence are common and
      require special attention. Late stage problems such as aspiration, difficulties
      with activities of daily living or recurrent falls require a multidisciplinary
      approach. Anticholinergic drugs such as benztropine and benzhexol are best
      avoided because of the high risk of major side effects.

PMID- 14650791
TI  - Is egg hypersensitivity a contraindication to influenza vaccine?

PMID- 14650792
TI  - Does she have a fatty liver?

PMID- 14650793
TI  - Thyroid eye disease. Eye series--10.

PMID- 14650794
TI  - Electronic decision support in general practice. What's the hold up?
AB  - BACKGROUND: The uptake of computers in Australian general practice has been for
      administrative use and prescribing, but the development of electronic decision
      support (EDS) has been particularly slow. Therefore, computers are not being used
      to their full potential in assisting general practitioners to care for their
      patients. OBJECTIVE: This article examines current barriers to EDS in general
      practice and possible strategies to increase its uptake. DISCUSSION: Barriers to
      the uptake of EDS include a lack of a business case, shifting of costs for data
      collection and management to the clinician, uncertainty about the optimal level
      of decision support, lack of technical and semantic standards, and resistance to
      EDS use by the time conscious GP. There is a need for a more strategic and
      attractive incentives program, greater national coordination, and more effective
      collaboration between government, the computer industry and the medical
      profession if current inertia is to be overcome.

PMID- 14650795
TI  - Sleep that knits the ravelled sleeve of care.

PMID- 14650796
TI  - Sexual dysfunction in the Australian population.
AB  - AIM: To describe the prevalence and forms of sexual dysfunction experienced by
      Australians, and compare these with people in the United States. METHODS: A cross
      sectional, telephone interview survey of a randomly selected sample of men (n =
      876) and women (n = 908) aged between 18 and 59 years on the electoral roll in
      all states and territories of Australia (response rate = 61%) was conducted
      between November 1999 and April 2000. RESULTS: Large proportions of Australian
      men (55.0%) and women (60.5%) reported at least one sexual problem within the
      preceding year. More serious sexual dysfunction (> 3 symptoms) was observed in
      13.2% of men and 19.7% of women. DISCUSSION: Australia and the USA are similar
      with regard to the high rate of symptoms of sexual dysfunction observed in the
      population. The low rate of treatment points to both patient and doctor
      reluctance to discuss sexual performance and practices.

PMID- 14650797
TI  - Pathways to care for psychological problems in primary care.

PMID- 14650799
TI  - Adult stem cell research, please.

PMID- 14650800
TI  - Tough choices.

PMID- 14650798
TI  - Building research capacity. An exploratory model of GPs' training needs and
      barriers to research involvement.
AB  - AIMS: To determine general practitioners' research training needs, and the
      barriers to involvement in research. METHOD: Semi-structured interviews with 11
      GPs in rural and metropolitan South Australia, analysed using a grounded theory
      approach. RESULTS: General practitioners' perceptions about their research needs
      were limited by their own experience and focussed at an individual level.
      Overlapping needs and barriers emerged, categorised as: 'individual issues' (a
      lack of research training or experience, concepts and attitudes to research, and
      research interest) and 'systems issues' (funding arrangements for general
      practice, access to resources, opportunity for publication and the role of The
      Royal Australian College of General Practitioners [RACGP]). DISCUSSION: Our data
      provide an exploratory model that may assist in developing suitable strategies
      for research capacity building programs. General practitioners perceived both
      individual and systems solutions to building research capacity, including
      multifaceted interventions.

PMID- 14650801
TI  - Out of time.

PMID- 14650802
TI  - Making the bite equal to the bark.

PMID- 14650803
TI  - Protecting the innocent.

PMID- 14650804
TI  - Newborn screening for congenital hypothyroidism: the Texas experience.
AB  - Routine screening of asymptomatic newborns allows detection and treatment of
      infants affected by congenital hypothyroidism. Implemented by legislation enacted
      in 1980, the Texas Newborn Screening Program detects 120-150 cases of primary
      hypothyroidism a year. The responsibility and, ultimately, the success of
      hypothyroid screening in the newborn period largely depends upon the medical
      provider, necessitating a clear understanding of the screening process,
      appropriate diagnostic tests for confirmation, and timely treatment.

PMID- 14650805
TI  - Please restore health care benefits.

PMID- 14650806
TI  - The logic of insurance.

PMID- 14650807
TI  - Aetna settlement a scam.

PMID- 14650808
TI  - Prompt pay.

PMID- 14650809
TI  - A win-win situation.

PMID- 14650810
TI  - Junk food junked.

PMID- 14650811
TI  - Stemming the tide of disease.

PMID- 14650812
TI  - The carrot and the stick.

PMID- 14650813
TI  - Health care fraud: recent developments and timeless advice.
AB  - Health care fraud has gained increased attention at both the state and federal
      levels in recent years. The $875 million criminal settlement by TAP
      Pharmaceutical Products, Inc, in October 2001 and subsequent indictments of
      physicians involved with the alleged HCA Medicare fraud conspiracy highlight the
      fact that physicians who are unaware of any wrongdoing may get dragged into the
      government's battle. The various laws and overlapping enforcement agencies can be
      complex and daunting to a physician who is falsely accused. This article provides
      a brief overview of three relevant federal health care fraud statutes: the
      Prescription Drug Marketing Act, the Medicaid Anti-Kickback Statute, and the
      False Claims Act. The article also briefly discusses the Texas Medicaid Fraud
      Prevention Act and the roles of various state agencies responsible for the
      detection and prevention of health care fraud. Finally, the article provides
      practical advice about the investigate process and what every prudent physician
      should do if under investigation.

PMID- 14650814
TI  - Diabetic renal failure in Texas: influence of ethnicity and household income.
AB  - Although end-stage renal disease (ESRD) remains a major public health problem in
      Texas, information regarding the influence of ethnicity and socioeconomic status
      on the prevalence of ESRD in Texas counties is limited. To determine whether
      ethnicity and a surrogate marker of socioeconomic status influence the prevalence
      of dialysis-related ESRD and of diabetic nephropathy ESRD (ESRD-DM) in Texas, we
      calculated indirect prevalence rates for each county by using 1998 data on 19,336
      patients in 80 counties. Using weighted multiple linear regression, we estimated
      ESRD and ESRD-DM ethnic prevalence. We estimated that among dialysis patients
      with ESRD, the indirect ethnic prevalence rate was highest for blacks, whereas
      when ESRD-DM was considered, Hispanics showed the highest prevalence, followed by
      blacks and then by non-Hispanic non-blacks. When the socioeconomic factor was
      incorporated into the regression model, the ESRD ethnic prevalence was highest
      for blacks living in poor counties and for Hispanics living in wealthy counties;
      however, for ESRD-DM, the ethnic prevalence rate was highest for Hispanics,
      whether they lived in poor or wealthy counties. Ethnicity and socioeconomic
      status accounted for 94% (93%) of the variation of ESRD (ESRD-DM) prevalence.
      This study may serve as a springboard for further investigation. Additional
      information, interventions, and resources are needed, particularly in the
      Southwest Hispanic region of the United States. Future annual reports from the US
      Renal Data System should include supplementary information on Hispanics.

PMID- 14650815
TI  - New perspectives in the treatment of tobacco dependence.
AB  - Tobacco dependance treatment is a long lasting journey that is now approaching
      the fifty-years landmark. Beginning with lobeline in the late Fifties, and
      passing through the development of nicotine replacement therapy, the
      pharmacological therapy of nicotine dependance has now reached a new phase of
      intense and florishing research. The purpose of this review is to briefly
      overview the history of tobacco dependence treatments and to lead the reader
      towards the future, not only in terms of drug therapy but also of new goals like
      relapse prevention strategies and smoking reduction. Neurobiology of drug
      addiction mechanisms better understanding has recently unmasked new therapeutical
      targets and has lead to the development of new drugs. Nicotine vaccine,
      tetrahydrocannabinoid receptor blockers, partial agonists for the nicotine
      receptors are now under evaluation. Interference with the liver enzymes
      metabolising nicotine is another approach who has just reached the testing phase.
      The article will briefly overview each of this new promising drug treatments.

PMID- 14650817
TI  - [Amiodarone and thyroid dysfunction: a pending problem].
AB  - Amiodarone is an antiarhytmic drug used in many clinical situations for its
      probed effect; it is also preferred in particular groups of patients (heart
      failure, post-ischemical) for its safe and its prognostic benefits. However, a
      substantial proportion of amiodarone treated patients develop either
      hypothyroidism or thyrotoxicosis. Both abnormalities may occur in apparently
      normal glands or in glandes with pre-existed abnormalities. It may be difficult
      to recognize the dysfunction because of the many changes in thyroid function test
      results that occur in euthyroid patients who are receiving amiodarone.
      Hypothyroidism is a well defined clinical situation managable thanks to common
      guidelines. The occurrence of hypothyroidism does not necessitate withdrawing
      amiodarone while instituting L-T4 replacement therapy, although many cases are
      transient and will spontaneously remit after amiodarone withdrawal. At the
      opposite, hyperthyroidism needs more attention to be diagnosed and to be treated,
      in fact there is a "personal" clinical-therapeutical behave towards it, caused by
      the lack of big trials made on this clinical situation. Effective strategies
      exist for the management of thyroid dysfunction, these should be tailored to the
      needs of the individual patient.

PMID- 14650816
TI  - [Guidelines for psychology activities in cardiologic rehabilitation and
      prevention].
AB  - The purpose of these guidelines is to provide specific recommendations in regard
      to psychological activities in cardiac rehabilitation (CR). Based on scientific
      evidence and clinical experience, the present guidelines are targeted for
      psychologists working in the field of cardiac rehabilitation and for the core
      component of CR, as well as for the health care providers, insurers, policy
      makers and consumers. In the introduction, the framework of Italian cardiac
      rehabilitation and psychology as well as the methodology used are defined, in
      accordance with the recommendations of the National Guidelines Programme of the
      Italian Health Ministry. The first section illustrates the educational training
      and structural requirements necessary for psychologists intending to work in
      cardiac rehabilitation, and provides a summary of the principal models of
      organization. Section two describes the sequence of psychological activities
      based on the different phases of the process of care. The chapters devoted to
      selection and admission of cardiac patients define the clinical conditions for
      which patients should be referred to the psychologist and describe the models for
      the first "patient-psychologist" contact. The chapter dedicated to evaluation,
      which aims to identify the care needs of the patient describes the instruments
      available to the psychologist (interview, screening tests, clinical assessment
      tests, quality-of-life tests) and the areas of investigation in cardiac diseases
      patients. The chapter on intervention analyses the different tools including
      educational interventions, counselling, stress management and psychotherapy
      evidenced by the literature and common to the different cardiac pathologies. In
      the chapter on follow-up, are described tools for evaluation of patient
      satisfaction and for planning long-term care. Section three describes the
      psychological characterization and the specificity of psychological interventions
      in different cardiac patients populations: patients with ischemic heart disease,
      patients after cardiac surgery, patients with chronic heart failure, patients
      after heart transplantation, patients with chronic peripheral artery disease,
      patients with pace-maker or implantable cardioverter defibrillator, high risk
      patients for cardiovascular disease, over 75 years of age and finally end-stage
      cardiac patients. The last section describes the processes of programme
      evaluation, audit and patient feedback as the main instruments recommended for
      continuous improvement of quality of psychological care in cardiac
      rehabilitation. The appendices contain a flow-chart describing the course of
      psychological interventions, a summary of recommendations for each cardiac
      condition and a glossary.

PMID- 14650818
TI  - [Cardiologic rehabilitation from the hospital to medical practice].

PMID- 14650819
TI  - [Communicating in health care: how mass-media can mislead].

PMID- 14650820
TI  - [Diagnostic and prognostic value of echocardiography in ischemic cardiopathy].

PMID- 14650821
TI  - Boario Home Care Project: an Italian telemedicine experience.
AB  - The use of telemedicine appears particularly promising in cardiovascular disease,
      because the cost/effectiveness ratio of an early, tailored intervention, in terms
      of life-saving and functional recovery is demonstrated. Boario Home Care project
      was born in 1998, with the aim of applying the new models of disease management
      and the new technology on the territory. In the first phase the project was to
      realize a telematic network for the General Practitioners in a mountain
      territory; In the second phase the project was extended to the regional and then
      national territory and the number of enrolled GPs increased. In the third phase,
      that is nowadays, the structure of the Service Center has been implemented with
      new broad band technologies (HDLS) and with an innovative teleworking model has
      been adopted for the professional figures involved. Four different types of
      services are now available: General Practitioners, Home Telenursing for chronic
      patients, Tele-diagnosis for palpitations and Call Center Services for hospitals.
      In conclusion, Boario Home Care project has reached its maturity and many results
      even if we can consider them preliminary in the field of Telemedicine. Boario
      Home Care project won e-health Awards with the honourable mention and it was
      presented at the "eHealth 2003: ICT for Health" in Brussels, Belgium.

PMID- 14650822
TI  - Range of pulmonary artery pressures in patients undergoing percutaneous atrial
      septal defect device closure.
AB  - The secundum type of atrial septal defect is one of the most common conditions
      associated with pulmonary arterial hypertension. In a series of 274 consecutive
      patients who have undergone percutaneous atrial septal defect device closure at
      our institution we observed an increase in pulmonary artery pressure with age,
      but only three patients had overt pulmonary arterial hypertension.

PMID- 14650823
TI  - Molecular genetics of kidney cancer.

PMID- 14650824
TI  - Mechanisms of immune dysfunction in renal cell carcinoma.

PMID- 14650825
TI  - New algorithms for the staging of kidney cancer.

PMID- 14650826
TI  - Basic biology and clinical behavior of renal cell carcinoma.

PMID- 14650827
TI  - Nephron-sparing surgery for renal cell carcinoma.

PMID- 14650828
TI  - Laparoscopic radical nephrectomy and minimally invasive surgery for kidney
      cancer.

PMID- 14650829
TI  - Role of nephrectomy in metastatic kidney cancer.

PMID- 14650830
TI  - Prognostic factors for metastatic kidney cancer.

PMID- 14650831
TI  - Interleukin-2 based therapy for kidney cancer.
AB  - In summary, IL-2 based therapy remains the basis for treatment of metastatic
      renal cell cancer. Un-answered questions remain in the development of regimens
      that exceed a mean response rate of 20%. Additionally, there may be differences
      among the histologic subtypes of renal cell cancer that predispose to response or
      lack there of to immunotherapy, and this is being further explored. As can be
      noted from the studies presented in this paper, there are numerous variations on
      the regimens for IL-2 based therapy. Current recommendations are to use the
      simplest and most feasible in a given institution. Certainly high dose IL-2
      remains the standard regimen to which all others are measured.

PMID- 14650832
TI  - The role of systemic chemotherapy in the treatment of kidney cancer.
AB  - Traditional cytotoxic chemotherapy has been considered to be ineffective in renal
      cell carcinoma, likely due to multiple mechanisms of high-level drug resistance
      proteins such as p-glycoprotein expressed by these cancers. Nonetheless, low
      level activity of several nucleoside analogues and the elucidation of critical
      molecular pathways and targets in this disease, such as the angiogenic pathway,
      provide hope that important advances can and will be made.

PMID- 14650833
TI  - Cell, gene and vaccine based strategies in kidney cancer.

PMID- 14650834
TI  - Monoclonal antibody therapy of kidney cancer.

PMID- 14650835
TI  - Allogeneic hematopoetic stem cell transplantation for cytokine refractory renal
      cell carcinoma.

PMID- 14650836
TI  - Novel therapies for renal cell carcinoma.

PMID- 14650837
TI  - Developmental plasticity of photoreceptors.
AB  - During development, retinal ganglion cells undergo conspicuous structural
      remodeling as they gradually attain their mature morphology and connectivity.
      Alterations in their dendritic organization and in their axonal projections can
      also be achieved following early insult to their targets or their afferents.
      Other retinal cell types are thought not to display this same degree of
      developmental plasticity. The present review will consider the evidence, drawn
      largely from recent experimental studies in the carnivore retina, that
      photoreceptors also undergo structural remodeling, extending their terminals
      transiently into inner plexiform layer before retracting to the outer plexiform
      layer. The determinants of this transient targeting to the inner plexiform layer
      are considered, and the role of cholinergic amacrine cells is discussed. The
      factors triggering this retraction are also considered, including the concurrent
      maturational changes in outer segment formation and in the differentiation of the
      outer plexiform layer. These results provide new insight into the life history of
      the photoreceptor cell and its connectivity, and suggest a transient role for the
      photoreceptors in the circuitry of the inner retina during early development,
      prior to the onset of phototransduction.

PMID- 14650838
TI  - Morphology and physiology of primate M- and P-cells.
AB  - Catarrhines and platyrrhines, the so-called Old- and New-World anthropoids, have
      different cone photopigments. Postreceptoral mechanisms must have co-evolved with
      the receptors to provide trichromatic color vision, and so it is important to
      compare postreceptoral processes in these two primate groups, both from
      anatomical and physiological perspectives. The morphology of ganglion cells has
      been studied in the retina of catarrhines such as the diurnal and trichromatic
      Macaca, as well as platyrrhines such as the diurnal, di- or trichromatic Cebus,
      and the nocturnal, monochromatic Aotus. Diurnal platyrrhines, both di- and
      trichromats, have ganglion cell classes very similar to those found in
      catarrhines: M (parasol), P (midget), small-field bistratified, and several
      classes of wide-field ganglion cells. In the fovea of all diurnal anthropoids, P
      cell dendritic trees contact single midget bipolars, which contact single cones.
      The Aotus retina has far fewer cones than diurnal species, but M- and P-cells are
      similar to those in diurnal primates although of larger size. As in diurnal
      anthropoids, in the Aotus, the majority of midget bipolar cells, found in the
      central 2 mm of eccentricity, receive input from a single cone and the sizes of
      their axon terminals match the sizes of P-cell dendritic fields in the same
      region. The visual responses of retinal ganglion cells of these species have been
      studied using single-unit electrophysiological recordings. Recordings from
      retinal ganglion cells in Cebus and Aotus showed that they have very similar
      properties as those in the macaque, except that P-cells of mono- and dichromatic
      animals lack cone opponency. Whatever the original role of the M- and P-cells
      was, they are likely to have evolved prior to the divergence of catarrhines and
      platyrrhines. M- and P-cell systems thus appear to be strongly conserved in the
      various primate species. The reasons for this may lie in the roles of these
      systems for both achromatic and chromatic vision.

PMID- 14650839
TI  - Identifying corollary discharges for movement in the primate brain.
AB  - The brain keeps track of the movements it makes so as to process sensory input
      accurately and coordinate complex movements gracefully. In this chapter we review
      the brain's strategies for keeping track of fast, saccadic eye movements. One way
      it does this is by monitoring copies of saccadic motor commands, or corollary
      discharges. It has been difficult to identify corollary discharge signals in the
      primate brain, although in some studies the influence of corollary discharge, for
      example on visual processing, has been found. We propose four criteria for
      identifying corollary discharge signals in primate brain based on our experiences
      studying a pathway from superior colliculus, in the brainstem, through
      mediodorsal thalamus to frontal eye field, in the prefrontal cortex. First, the
      signals must originate from a brain structure involved in generating movements.
      Second, they must begin just prior to movements and represent spatial attributes
      of the movements. Third, eliminating the signals should not impair movements in
      simple tasks not requiring corollary discharge. Fourth, eliminating the signals
      should, however, disrupt movements in tasks that require corollary discharge,
      such as a double-step task in which the monkey must keep track of one saccade in
      order to correctly generate another. Applying these criteria to the pathway from
      superior colliculus to frontal eye field, we concluded that it does indeed convey
      corollary discharge signals. The extent to which cerebral cortex actually uses
      these signals, particularly in the realm of sensory perception, remains unknown
      pending further studies. Moreover, many other ascending pathways from brainstem
      to cortex remain to be explored in behaving monkeys, and some of these, too, may
      carry corollary discharge signals.

PMID- 14650840
TI  - Visual awareness and the cerebellum: possible role of decorrelation control.
AB  - The two roles in awareness most often suggested for the cerebellum are (i)
      keeping the details of motor skills away from forebrain computation, and (ii)
      signaling to the forebrain when a sensory event is not predictable from prior
      motor commands. However, it is unclear how current models of the cerebellum could
      carry out these roles. Their architecture, based on the seminal ideas of Marr and
      Albus, appears to need 'motor error' to learn correct motor commands. However,
      since motor error is the difference between the actual motor command and what the
      command should have been, it is a signal unavailable to the organism in
      principle. We propose a possible solution to this problem, termed decorrelation
      control, in which the cerebellum learns to decorrelate the motor command sent to
      the muscles from the sensory consequences of motor error. This method was tested
      in a linear model of oculomotor plant compensation in the vestibulo-ocular
      reflex. A copy of the eye-movement command was sent as mossy-fiber input to the
      flocculus, represented as a simple adaptive filter version of the Marr-Albus
      architecture. The sensory consequences of motor error were retinal slip,
      delivered as climbing fiber input to the flocculus. A standard anti-Hebbian
      learning rule was used to decorrelate the two. Simulations of the linearized
      problem showed the method to be effective and robust for plant compensation.
      Decorrelation control is thus a candidate algorithm for the basic cerebellar
      microcircuit, indicating how it could achieve motor learning using only signals
      available to the system. Such learning might then enable the cerebellum to free
      up visual awareness, and also, by providing a sensory signal decorrelated from
      motor command, supply awareness with crucial information about the external
      world.

PMID- 14650841
TI  - Some effects of cortical and callosal damage on conscious and unconscious
      processing of visual information and other sensory inputs.
AB  - Although new methods of investigation from the molecular level to cognition are
      promoting major advances in the study of the functions of the human brain, the
      analysis of behavioral and psychological deficits following brain damage is still
      a major tool for the understanding of cerebral organization. The present paper
      reviews some aspects of work on functional losses and residual abilities
      following cortical damage that have allowed to distinguish conscious and
      unconscious levels of visual input processing. Attention is given to the possible
      contribution of residual conscious vision of color to unconscious form analysis
      in visual agnosia. The paper also reviews findings on temporary and permanent
      deficits that occur after selective lesions of a prominent input-output system of
      the cerebral cortex, the corpus callosum, with the aim of assessing the
      possibility of establishing a functional callosal topography.

PMID- 14650842
TI  - Consciousness absent and present: a neurophysiological exploration.
AB  - Backward masking was used to investigate the amount of neuronal activity that
      occurs in the macaque inferior temporal visual cortex when faces can just be
      identified. It is shown that the effect of the pattern mask is to interrupt
      neuronal activity in the inferior temporal visual cortex. This reduces the number
      of action potentials that occur to a given stimulus, and decreases even more the
      information that is available about which stimulus was shown because the variance
      of the spike counts is increased. When the onset of the mask follows the onset of
      the test stimulus by 20 ms, each neuron fires for approximately 30 ms, provides
      on average 0.06 bits of information, and human observers perform at approximately
      50% better than chance in forced choice psychophysics, yet say that they are
      guessing, and frequently report that they are unable to consciously see the face
      and identify which face it is. At a longer Stimulus Onset Asynchrony of 40 ms,
      the neurons fire for approximately 50 ms, the amount of information carried by a
      single neuron is 0.14 bits, and human observers are much more likely to report
      conscious identification of which face was shown. The results quantify the amount
      of neuronal firing and information that is present when stimuli can be
      discriminated but not reported on consciously, and the additional amount of
      neuronal firing and information that is required for humans observers to
      consciously identify the faces. It is suggested that the threshold for conscious
      visual perception may be set to be higher than the level at which small but
      significant information is present in neuronal firing, so that the systems in the
      brain that implement the type of information processing involved in conscious
      thoughts are not interrupted by small signals that could be noise in sensory
      pathways.

PMID- 14650843
TI  - Rapid serial visual presentation for the determination of neural selectivity in
      area STSa.
AB  - We show that rapid serial visual presentation (RSVP) in combination with a
      progressive reduction of the stimulus set is an efficient method for describing
      the selectivity properties of high-level cortical neurons in single-cell
      electrophysiological recording experiments. Rapid presentation allows the
      experimental testing of a significantly larger number of stimuli, which can
      reduce the subjectivity of the results due to stimulus selection and the lack of
      sufficient control stimuli. We prove the reliability of the rapid presentation
      and stimulus reduction methods by repeated experiments and the comparison of
      different testing conditions. Our results from neurons in area STSa of the
      macaque temporal cortex provide a well-controlled confirmation for the existence
      of a population of cells that respond selectively to stimuli containing faces.
      View tuning properties measured using this method also confirmed earlier results.
      In addition, we found a population of cells that respond reliably to complex non
      face stimuli, though their tuning properties are not obvious.

PMID- 14650844
TI  - Cortical interactions in vision and awareness: hierarchies in reverse.
AB  - The anatomical connections between visual areas can be organized in
      'feedforward', 'feedback' or 'horizontal' laminar patterns. We report here four
      experiments that test the function of some of the feedback projections in visual
      cortex. Projections from V5 to V1 have been suggested to be important in visual
      awareness, and in the first experiment we show this to be the case in the
      blindsight patient GY. This demonstration is replicated, in principle, in the
      second experiment and we also show the timing of the V5-V1 interaction to
      correspond to findings from single unit physiology. In the third experiment we
      show that V1 is important for stimulus detection in visual search arrays and that
      the timing of V1 interference with TMS is late (up to 240 ms after the onset of
      the visual array). Finally we report an experiment showing that the parietal
      cortex is not involved in visual motion priming, whereas V5 is, suggesting that
      the parietal cortex does not modulate V5 in this task. We interpret the data in
      terms of Bullier's recent physiological recordings and Ahissar and Hochstein's
      reverse hierarchy theory of vision.

PMID- 14650845
TI  - Two distinct modes of control for object-directed action.
AB  - There are multiple routes from vision to action that play a role in the
      production of visually guided reaching and grasping. What remain to be resolved,
      however, are the conditions under which these various routes are recruited in the
      generation of actions and the nature of the information they convey. We argue in
      this chapter that the production of real-time actions to visible targets depends
      on pathways that are separate from those mediating memory-driven actions.
      Furthermore, the transition from real-time to memory-driven control occurs as
      soon as the intended target is no longer visible. Real-time movements depend on
      pathways from the early visual areas through to relatively encapsulated
      visuomotor mechanisms in the dorsal stream. These dedicated visuomotor
      mechanisms, together with motor centers in the premotor cortex and brainstem,
      compute the absolute metrics of the target object and its position in the
      egocentric coordinates of the effector used to perform the action. Such real-time
      programming is essential for the production of accurate and efficient movements
      in a world where the location and disposition of a goal object with respect to
      the observer can change quickly and often unpredictably. In contrast, we argue
      that memory-driven actions make use of a perceptual representation of the target
      object generated by the ventral stream. Unlike the real-time visuomotor
      mechanisms, perception-based movement planning makes use of relational metrics
      and scene-based coordinates. Such computations make it possible, however, to plan
      and execute actions upon objects long after they have vanished from view.

PMID- 14650846
TI  - Color contrast: a contributory mechanism to color constancy.
AB  - Color constancy--by which objects tend to appear the same color under changes in
      illumination--is most likely achieved by several mechanisms, operating at
      different levels in the visual system. One powerful contributory mechanism is
      simultaneous spatial color contrast. Under changes in natural illumination the
      spatial ratios of within-type cone excitations between natural surfaces tend to
      be preserved (Foster and Nascimento, 1994); therefore, the neural encoding of
      colors as spatial contrasts tends to achieve constancy. Several factors are known
      to influence the strength of chromatic contrast induction between surfaces,
      including their relative luminance, spatial scale, spatial configuration and
      context (Ware and Cowan, 1982; Zaidi et al., 1991). Here we test the hypothesis
      that color contrast is weakened by differences between surfaces which indicate
      that they may be under distinct illuminants. We summarize psychophysical
      measurements of the effects of relative motion, relative depth and texture
      differences on chromatic contrast induction. Of these factors, only texture
      differences between surfaces weaken chromatic contrast induction. We also
      consider neurophysiological and neuropsychological evidence and conclude that the
      mechanisms which mediate local chromatic contrast effects are sited at low levels
      in the visual system, in primary visual cortex (V1) or below, prior to image
      segmentation mechanisms which require computation of relative depth or motion. V1
      and lower areas may therefore play a larger role in color constancy than
      previously thought.

PMID- 14650848
TI  - Neuroimaging studies of attention and the processing of emotion-laden stimuli.
AB  - Because the processing capacity of the visual system is limited, selective
      attention to one part of the visual field comes at the cost of neglecting other
      parts. In this paper, we review evidence from single-cell studies in monkeys and
      functional magnetic resonance imaging (fMRI) studies in humans for neural
      competition and how competition is biased by attention. We suggest that, at the
      neural level, an important consequence of attention is to enhance the influence
      of behaviorally relevant stimuli at the expense of irrelevant ones, providing a
      mechanism for the filtering of distracting information in cluttered visual
      scenes. Psychophysical evidence suggests that processing outside the focus of
      attention is attenuated and may be even eliminated under some conditions. A major
      exception to the critical role of attention may be in the neural processing of
      emotion-laden stimuli, which are reported to be processed automatically, namely,
      without attention. Contrary to this prevailing view, in a recent study we found
      that all brain regions responding differentially to faces with emotional content,
      including the amygdala, did so only when sufficient resources were available to
      process those faces. After reviewing our findings, we discuss their implications,
      in particular (1) how emotional stimuli can bias competition for processing
      resources; (2) the source of the biasing signal for emotional stimuli; (3) how
      visual information reaches the amygdala; and finally (4) the relationship between
      attention and awareness.

PMID- 14650849
TI  - Selective visual attention, visual search and visual awareness.
AB  - In a previous study, Butter and Goodale (2000) reported that visual search
      increases the identification of targets relative to distracters. The present
      series of studies investigated further this effect of search. Search increased
      identification of Ls when they were targets and decreased their identification
      when Ls were distracters in concurrent search involving feature conjunctions
      (Exp. 1). Subjects in Experiment 2 showed increases in sensitivity, but not in
      response bias, to Ls. Search had a weaker effect on d' for identification of Ts.
      Increasing the difficulty of searching for Ts or Ls by increasing the number of
      distracters enhanced identification of targets versus distracters relative to the
      effect of search involving eight distracters (Exp. 3). Two studies investigated
      the effects on probe identification of easy search tasks involving differences in
      stimulus features. In Experiment 4, there were no reliable effects of search on
      probe identification when targets were distinguished from distracters by straight
      versus curved lines (Z vs. O). When horizontal and vertical lines were targets
      and distracters, subjects showed weak and inconsistent effect on probe
      identification (Exp. 5). These findings, together with results of
      neurophysiological studies, support the view that executive mechanisms play a
      role in visual search by augmenting the activity of goal representations in
      working memory, thus increasing the likelihood of identifying goal stimuli and
      enhancing the efficiency of visual search.

PMID- 14650847
TI  - The primacy of chromatic edge processing in normal and cerebrally achromatopsic
      subjects.
AB  - The local chromatic contrast between surfaces in a visual scene plays an
      important role in theories of color perception. Our studies of cerebral
      achromatopsia suggest that this contrast signal is computed independently of the
      more complex processes such as edge integration and anchoring. We report a study
      in which we attempted to determine whether local-contrast signals also drove
      behavior in normal subjects. We sought to reduce the role of edge integration and
      anchoring by using stimuli whose background varied very gradually in color from
      top to bottom. The local chromatic contrast of patches relative to such
      backgrounds depends upon the position at which they are presented. It is
      therefore possible for patches with identical spectral composition to have
      opposite contrasts. We constructed stimuli in which two of three vertically
      arranged discs had the same contrast while the third had opposite contrast. The
      stimuli were also constructed so that the contrast-odd disc and one of the other
      two had identical spectral composition while the third disc had different
      composition. We used these stimuli in an attentional task where, after a brief
      delay, a letter discrimination target was presented in the location of one of the
      discs. Attention should automatically be attracted to the odd disc in such a
      display. Normal observers were faster at making the letter discrimination when
      the target appeared at the contrast-odd as opposed to spectrally odd location. We
      conclude that local chromatic contrast, but not raw spectral composition, is
      accessible to normal observers at an appropriate stage in visual processing to
      drive attention.

PMID- 14650850
TI  - First-order and second-order motion: neurological evidence for neuroanatomically
      distinct systems.
AB  - An unresolved issue in visual motion perception is how distinct are the processes
      underlying 'first-order' and 'second-order' motion. The former is defined by
      spatio-temporal variations of luminance and the latter by spatio-temporal
      variations in other image attributes such as contrast or depth, for example.
      Using neuroimaging and psychophysics we present data from four neurological
      patients with unilateral and mostly cortical infarcts, which strongly suggest
      that first- and second-order motion have a different neural substrate. We found
      that from the early stages of processing, these two types of motions are mediated
      by two distinct pathways: first-order motion is carried out by mechanisms along
      the dorsal pathway in the occipital lobe, while the second-order motion by
      mechanisms mostly along the ventral pathway. The data reported here also suggest
      that different cortical regions may be in charge of processing direction
      discrimination in second-order motion defined by different second-order
      attributes.

PMID- 14650851
TI  - Reaching between obstacles in spatial neglect and visual extinction.
AB  - The aim of the present studies was to investigate whether 'perception' and
      'visually guided action' could be dissociated with regard to two different
      aspects of the neglect syndrome. In the first study we tested a group of patients
      with neglect in two tasks, both within the same experimental setting. One task
      was to bisect a space between two objects, while the other required subjects to
      reach between the same pair of objects en route to a target area, so that the
      objects became potential obstacles to the reach. In the second study we tested a
      patient with visual extinction to double simultaneous stimulation, using a
      similar reaching task. Our aim was to determine whether visual awareness of
      obstacles in the workspace was necessary for successful navigation. In both
      studies we found evidence that reaching responses took normal account of the
      presence and location of obstacles on the left side, despite the tendency to
      neglect such left-sided information in more explicit perceptual tasks. We
      interpret both sets of results within a theoretical framework that identifies on
      line visuomotor control with the occipito-parietal 'dorsal stream' (along with
      associated premotor and subcortical structures), and visual perception with the
      occipito-temporal 'ventral stream', plus associated temporo-parietal areas.

PMID- 14650852
TI  - Roots of blindsight.
AB  - The chapter reviews the historical background to demonstrations that there is
      residual visual function in the total absence of striate cortex (V1) in monkey
      and humans. The late 19th century evidence by Munk and others, as reviewed by
      William James, was that this was not possible in humans, and doubtful at best in
      monkeys. It has gradually become realized, starting in the middle of the 20th
      century, that even total bilateral removal of striate cortex in monkeys does not
      abolish all visual capacity, including spatial and pattern vision. The situation
      regarding unilateral or incomplete bilateral lesions in the monkey did not become
      clarified until Cowey's doctoral work in the 1960s, demonstrating that field
      defects were not absolute, that sensitivity continued to improve over several
      months of postoperative testing, that the size of the field defect gradually
      shrank, that the sensitivity was poorest at the center of the field defect, and
      that recovery was not spontaneous but depended on sustained practice. In human
      subjects with unilateral lesions from the 1970s onwards, using forced-choice
      methodology parallel to animal studies, a wide range of visual discriminations
      was demonstrated but with alterations or complete absence of acknowledged
      awareness by subjects (blindsight). Various varieties of skepticism are discussed
      and rebutted. The gap between humans and animals was diminished by the
      demonstration by Cowey and Stoerig that monkeys, like humans, classify responses
      to blind-field stimuli as being 'unseen'. Further recent degrees of closure and
      developments in human blindsight research are discussed.

PMID- 14650853
TI  - 'Double-blindsight' revealed through the processing of color and luminance
      contrast defined motion signals.
AB  - Background perturbation techniques using both static and dynamic luminance
      contrast and chromatic contrast noise have been employed to investigate the
      interaction between luminance and chromatic contrast signals. A number of
      experiments involving contrast detection thresholds for static stimuli, simple
      reaction times, and pupil color responses yield evidence for independent
      processing of luminance and color signals. One exception is the perception of
      color-defined coherent motion of randomly distributed checks when dynamic,
      luminance-defined, motion signals can disrupt completely the perception of
      coherent motion. When the moving stimulus contains color-defined, recognizable
      features that are spatially distinct from background noise, the perception of
      coherent motion is restored and becomes completely independent of dynamic
      luminance contrast noise. Feature-tracking mechanisms must therefore play a major
      part in the detection of color-defined motion. Other findings reveal the
      existence of a motion channel that receives exclusively achromatic inputs and a
      separate channel that extracts and combines luminance contrast and color-defined
      motion signals. Further studies carried out to investigate the interaction
      between luminance and chromatic signals show that color-defined, position-change
      thresholds are mediated by motion detection mechanisms and are, therefore, also
      disrupted by dynamic luminance contrast noise. In spite of the perceived
      uncertainty of spatial location, other experiments show that accurate, color
      defined position information is preserved and available for use in other tasks.
      For example, accurate position information can be used to detect the vertical
      misalignment of color-defined checks, independently of luminance contrast noise,
      even when position-change thresholds are severely impaired. The analogy with
      'blindsight' is obvious and irresistible. 'Blindsight' describes the ability to
      make accurate use of visual information in the absence of conscious visual
      perception. The findings that have emerged from this investigation reveal the
      ability of normal subjects to discard misleading, consciously perceived visual
      signals. The ability to override perception and to make good use of accurate
      visual information, in spite of misleading percepts, can best be described as
      'Double-blindsight'.

PMID- 14650854
TI  - Stimulus cueing in blindsight.
AB  - When visual stimuli are presented in the cortically blind visual field of
      patients or monkeys with verified destruction of striate cortex, many subjects
      can voluntarily respond to them. In studies of this blindsight, the on- and/or
      offset of the visual stimulus is usually known to the subject, either because it
      is signaled in some way or because the subject can present the stimulus himself.
      To study the effect of stimulus uncertainty on the responses of four hemianopic
      monkeys and one human hemianope, we compared trials on which the subjects
      themselves could instantly trigger the stimulus with trials on which the same
      stimulus appeared 1-7 s after the start-light that normally served as the trigger
      was first touched. The latter manipulation diminished both the percentage of
      trials on which the subjects responded and the percentage correct when they did
      respond. As the start-light disappeared when touched in the first but not second
      condition, we interpret our results as indicating an influential role for
      attention in blindsight. Although keeping attention focused on the start-light
      and delaying the target impaired performance especially in the monkeys,
      localization was still significant in three and hardly affected in GY.

PMID- 14650855
TI  - Visually guided behavior after V1 lesions in young and adult monkeys and its
      relation to blindsight in humans.
AB  - After lesions of striate cortex in primates, there is still the capacity to
      detect and localize visual stimuli. In this chapter we review three aspects of
      our study of this phenomenon in macaques. First, we found that macaques that
      received their striate lesions as infants had considerably greater ability to
      detect and localize stimuli than those that received similar lesions as adults.
      Second, we suggest that the visual functions that survive striate lesions in
      macaques made in adulthood resemble those in human 'blindsight'. Third, we report
      that monkeys with striate lesions made in infancy are able to discriminate
      direction of visual motion.

PMID- 14650856
TI  - Is blindsight in normals akin to blindsight following brain damage?
AB  - The aim of this chapter is to discuss evidence bearing on two related issues,
      namely, first, whether the neural pathways of subliminal perception are the same
      as those subserving suprathreshold perception. Second, whether the pathways for
      subliminal perception in normals are similar to those subserving blindsight in
      brain-damaged patients. As to the former question, the overall balance is in
      favor of the different-pathway hypothesis while a tentative answer to the second
      question might be that blindsight is basically similar to subliminal perception
      in normals. The differences undoubtedly existing between the two conditions
      depend mainly on the differences in the stimuli used to reveal them.

PMID- 14650857
TI  - Auras and other hallucinations: windows on the visual brain.
AB  - Hallucinations in psychologically normal individuals provide a valuable route to
      studying the neural mechanisms of visual awareness. Migraine auras, epileptic
      auras and the hallucinations of Charles Bonnet Syndrome are examined in this
      context. Both similarities and striking differences in content are noted and the
      extent to which we are currently able to localize the source of these forms of
      endogenously driven visual awareness is discussed.

PMID- 14650858
TI  - Theories of visual awareness.
AB  - The past decade has provided a wealth of data for theorists of visual awareness.
      Two empirical approaches, both seeking to dissociate conscious from unconscious
      neural processes, have been particularly fruitful. The first has focused on the
      neural correlates of changes in experience occurring in the absence of change in
      external stimuli, for example during binocular rivalry; the second has
      investigated the neural correlates of unconscious processes such as blindsight.
      Several of the theories based on these data propose that visual consciousness
      arises from interactions between thalamo-cortical modules whose independent
      operation is unconscious; popular candidate 'modules' include visual regions in
      the 'ventral' visual pathway and parieto-frontal regions associated with action
      planning. These theories can be tested against recent findings from patients in
      the vegetative state, a state of 'wakefulness without awareness', which can
      follow major insults to the brain. The findings indicate that stimulus-evoked
      cortical activity occurs in the vegetative state, but tends to be limited in
      extent, is often restricted to primary sensory areas, and is poorly integrated
      with activity elsewhere in the cerebrum. The theories of visual awareness
      reviewed previously predict that such activity should not give rise to visual
      experience. This prediction is reassuring, but can we be sure that it is correct?
      Reflection on the indirect nature of the evidence available to theorists of
      visual awareness makes it doubtful that we can confidently specify the minimum
      conditions for awareness, unless we are prepared to modify our everyday concept
      of consciousness. O'Regan and Noe have recently proposed a sophisticated
      redefinition of visual awareness along these lines. Progress at this frontier of
      visual neuroscience requires that scientists and philosophers join forces to
      clarify the concepts of experience and consciousness.

PMID- 14650859
TI  - Venous thromboembolism: pathophysiology and clinical presentation.
AB  - Venous thromboembolism (VTE) is associated with short- and long-term morbidity
      and mortality. Strategies to identify and stratify patients at risk for VTE and
      guidelines for its prevention are discussed. VTE, which includes deep venous
      thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal
      health problem. An estimated 2 million patients in the United States will develop
      a DVT annually. Although VTE is asymptomatic in many patients, the risk of
      mortality remains high--approximately 100,000 deaths annually in the United
      States--despite the availability of effective treatments. Many patients who
      initially survive a PE die within 90 days of discharge. VTE is also associated
      with long-term consequences, such as recurrent VTE and the disabling and costly
      postthrombotic syndrome (PTS). VTE produces a significant economic burden due not
      only to the direct medical costs associated with acute inpatient care but also to
      the long-term, follow-up costs. The routine use of prophylaxis to prevent VTE is
      justified due to high prevalence, asymptomatic nature, long-term morbidity, high
      mortality rate, and cost of the disorder. Health-system pharmacists can help to
      diminish the risk of VTE by identifying and stratifying at-risk patients and
      ensuring that appropriate prophylaxis is provided. Implementing a methodical and
      aggressive approach will reduce the incidence as well as the morbidity,
      mortality, and cost associated with VTE.

PMID- 14650860
TI  - Clinical trials with factor Xa inhibition in the prevention of postoperative
      venous thromboembolism.
AB  - Factor Xa inhibition is a selective mechanism used for anticoagulation therapy.
      Clinical trials of drugs designed to inhibit factor Xa for the prevention of
      venous thromboembolism (VTE) after major orthopedic surgery are discussed.
      Hemostasis is a balanced process of blood coagulation and clot dissolution.
      Factor Xa is located at a key point in the clotting cascade, since it bridges the
      extrinsic and intrinsic pathways of this process. Inhibition of factor Xa via
      antithrombin (AT) by fondaparinux has been studied extensively. Fondaparinux
      selectively binds to AT, producing rapid anticoagulation with an approximate 300
      fold potentiation of the natural inhibitory activity of AT against factor Xa. The
      anticoagulant demonstrates a linear dose response and is eliminated renally.
      Comparative trials conducted in major hip and knee surgeries established the
      efficacy and safety of fondaparinux in this setting. Overall, fondaparinux
      significantly reduced the incidence of VTE by day 11 (6.8%) compared with
      enoxaparin (13.7%)--common odds reduction of 55.2%. No difference in the
      incidence of clinically relevant bleeding (e.g, major bleeding leading to death
      or reoperation, or occurring in a critical organ) was observed. An increase in
      the occurrence of major bleeding was observed when the first dose was
      administered prior to 6 hours after surgical closure, resulting in the
      recommendation that the first dose be given 6 to 8 hours postsurgically. With
      strict adherence to recommendations for its use, fondaparinux may be used safely
      in certain special populations. Results from these large controlled trials
      predict that this factor Xa inhibitor will receive the highest recommendation in
      subsequent evidence-based guidelines for the prevention of VTE following major
      hip and knee surgeries, including surgery for hip fracture repair.

PMID- 14650861
TI  - Pharmacoeconomic considerations.
AB  - Pharmacoeconomic analyses can be readily applied to the study of venous
      thromboembolism (VTE) in the orthopedic postsurgical setting. The cost of VTE to
      the health care system and a cost-effectiveness trial that utilized a factor Xa
      inhibitor for VTE prophylaxis are discussed. The rationale for preventing VTE can
      be justified by its high frequency, asymptomatic nature, and high morbidity and
      mortality that result from unprevented thromboemboli. However, the economic
      burden that results from VTE is indeed significant. More effective antithrombotic
      prophylaxis would reduce the occurrence of VTE, the incidence of complications,
      and subsequent costs. Previous pharmacoeconomic analyses underscore the financial
      burden VTE places on the health care system in terms of increased length of
      hospital stay, time spent in the intensive care unit, and mean total cost. Trial
      based and effectiveness-based analyses were utilized to compare the cost
      effectiveness of a 7-day regimen of fondaparinux (2.5 mg once daily) and
      enoxaparin (30 mg twice daily). In the trial-based analysis, fondaparinux was
      estimated to prevent 15.1 thromboembolic events per 1000 patients at three months
      compared with enoxaparin; fondaparinux produced cost savings per patient at 30
      days, 3 months, and 5 years postdischarge. In the effectiveness analysis,
      fondaparinux was estimated to prevent 17.7 thromboembolic events per 1000
      patients at 3 months compared with enoxaparin; fondaparinux produced cost savings
      per patient at discharge, 1 month, 3 months, and 5 years postdischarge. These
      analyses demonstrate fondaparinux to be cost-effective for the prophylaxis of VTE
      in the orthopedic postsurgical setting.

PMID- 14650862
TI  - Novel concepts: emerging data and the role of extended prophylaxis following hip
      fracture surgery.
AB  - The typical duration of hospitalization following major knee and hip surgeries
      may not provide adequate time for effective prophylaxis of venous thromboembolism
      (VTE) when inpatient therapy only is administered. Results from a clinical trial
      that extended the duration of VTE prophylaxis after hip fracture surgery are
      reviewed. The risk of VTE after major knee and hip arthroplasty has been
      demonstrated to extend into the outpatient period. Although extending the
      duration of VTE prophylaxis has been demonstrated to decrease the incidence of
      VTE following total hip replacement, no randomized, double-blinded assessment had
      demonstrated the effectiveness of this strategy following hip fracture surgery. A
      multicenter, randomized, placebo-controlled, double-blind trial was conducted to
      assess prolonged prophylaxis of VTE in patients undergoing surgery for fracture
      of the upper third of the femur. Patients received an initial 7 +/- 1 day open
      period of treatment with subcutaneous fondaparinux (2.5 mg once daily); 656
      patients were subsequently randomized to receive a 21 +/- 2-day double-blind
      treatment period of either the same fondaparinux regimen or placebo. Fondaparinux
      treatment produced statistically significant reductions in the incidence of all
      VTE events (1.4% compared with placebo 35.0%); prolonged prophylaxis was
      associated with a 96% relative risk reduction for VTE (p < 0.001). Also, no
      differences were observed in the incidence of other major endpoints such as
      bleeding or death. These results indicate that extended prophylaxis with
      fondaparinux significantly reduces the risk of VTE without increasing the risk of
      major bleeding.

PMID- 14650863
TI  - Future therapeutic directions for factor Xa inhibition in the prophylaxis and
      treatment of thrombotic disorders.
AB  - The targeted mechanism of factor Xa inhibition has been studied extensively,
      initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic
      surgical setting. Future therapeutic directions for selective factor Xa
      inhibition in the management of other thrombotic diseases are discussed.
      Thromboembolic diseases can occur in the venous or arterial sides of the
      circulatory system. Factor Xa inhibition is a targeted approach to
      anticoagulation that resulted from significant advances in our understanding of
      the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied
      extensively in the orthopedic surgical setting for the prophylaxis of VTE.
      Current investigations that are under way or completed evaluate the efficacy and
      safety of fondaparinux for the management of various thrombotic diseases. The
      future development of fondaparinux resides primarily in three therapeutic areas:
      prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes.
      For the prevention of VTE, fondaparinux has been studied as extended prophylaxis
      following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal
      surgical patients (PEGASUS and APOLLO), and for use in medical patients
      (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of
      the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was
      investigated in phase 2 studies for the treatment of acute coronary syndromes,
      including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina
      (PENTUA). Encouraging data from these trials are the basis for phase 3 programs
      in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic
      clinical programs for fondaparinux in the management of thrombosis support the
      concept that targeted inhibition of coagulation is an effective advance in
      antithrombotic therapy.

PMID- 14650864
TI  - The influence of adrenergic receptor block on the cardiovascular effects of the
      lipopolysaccharide from Salmonella typhimurium.

PMID- 14650865
TI  - The adrenalin-mediated activation of expression of the 70-kDa heat-shock protein
      in the population of thymocytes.

PMID- 14650866
TI  - Sprouting and electric activity parameters of the rat sensorimotor cortex after
      damaging a symmetric part of the contralateral hemisphere.

PMID- 14650867
TI  - Sensitivity of dolphin's hearing as a function of the sound-source position.

PMID- 14650868
TI  - The potentiation of hippocampal responses at positive membrane potential reveals
      the presynaptic nature of the low efficacy of "silent" synapses.

PMID- 14650870
TI  - Spatiotemporal analysis of the contraction of a fragment of the unfolded frog
      atrium.

PMID- 14650869
TI  - The role of cAMP as a primary and secondary messenger in interactions between
      micro- and macroorganisms studied in the model of pathology related to
      immunodeficiency and extensive cell dehydration.

PMID- 14650871
TI  - The use of ethnic portraiture for predicting individual sensitivity to chemicals
      as exemplified by N-acetylation in cancer patients.

PMID- 14650872
TI  - Bat (Vespertilionidae) hibernation in the northeasternmost part of their
      geographic range.

PMID- 14650873
TI  - Evaluation of winter activity of soil invertebrates.

PMID- 14650874
TI  - On the stimulatory effect of neuromediators on the root pumping activity.

PMID- 14650875
TI  - Periodic structure of surface fields of the net atmospheric protein aerosol
      concentration in the outskirts of the city of Novosibirsk.

PMID- 14650877
TI  - Subfossil Oribatid mites in the holocene deposits of the Arkhangel'sk oblast.

PMID- 14650876
TI  - Juvenile hormone regulates oviposition in Drosophila exposed to heat stress.

PMID- 14650878
TI  - Some theoretical problems of cloning in the light of comparative analysis of
      early development in mammals.

PMID- 14650879
TI  - Assessment of the rate of 241Am americium release from the biomass of aquatic
      plants of the Yenisei River.

PMID- 14650880
TI  - The enzymatic activity of the gastrointestinal tract microflora of the greater
      mole rat (Spalax microphtalmus, Spalacidae, Rodentia).

PMID- 14650881
TI  - Evaluation of the effects of drought on cotton plants using characteristics of
      chlorophyll fluorescence.

PMID- 14650882
TI  - Mechanism of defensive morph formation in Euplites aediculatus (Ciliate,
      Hypotrichida).

PMID- 14650883
TI  - Activity rhythms in weakly electric fish.

PMID- 14650884
TI  - A phenomenological mathematical model of the effect of biomanipulation (removal
      of planktivorous fish) on the biomass of cyanobacteria in a small pond.

PMID- 14650885
TI  - Ubiquitinylation and proteasome-dependent degradation of the phosphoinositide
      specific phospholipase C gamma 1 in A-431 cells.

PMID- 14650886
TI  - Irradiation of tubulin solution in vitro by electrons causes self-assembly of
      tubulin into microtubules in the absence of magnesium cations.

PMID- 14650887
TI  - Genetic instability of male gametes in long-lived mice of the SAMP1 strain prone
      to accelerated aging.

PMID- 14650888
TI  - Morphometric analysis of cardiomyocytes of the rat heart left ventricle under
      simulated weightlessness.

PMID- 14650889
TI  - New neurogenes in mammals.

PMID- 14650890
TI  - Proliferation block and mitotic pathology in cells infected with cytomegalovirus:
      the role of the cell cycle stage at the moment of infection.

PMID- 14650892
TI  - Diabetes--a review.

PMID- 14650891
TI  - Opposite effects of low oligomycin concentrations on the apoptosis of normal and
      tumor cells.

PMID- 14650893
TI  - Inhalant abuse: information for parents.

PMID- 14650894
TI  - An opportunity for school nurses and pediatricians to collaborate.

PMID- 14650895
TI  - Keys to helping socially-anxious teenagers.

PMID- 14650896
TI  - School refusal behavior.

PMID- 14650897
TI  - Community approaches to a national problem: oral health. Part 2.

PMID- 14650898
TI  - Medical management needs of children with diabetes at school.

PMID- 14650899
TI  - Schools: the hub of the wheel for CPR/AED programs in the school and the
      community.

PMID- 14650900
TI  - Rhabdomyolysis: an overview and study of outcomes in smoking and non-smoking
      patients at WVU hospitals.
AB  - The purpose of this study was to review the etiology, diagnosis, treatment, and
      outcomes of cases of rhabdomyolysis at West Virginia University Hospitals.
      Another goal was to determine if smokers had worse outcomes than non-smokers.
      Rhabdomyolysis was defined as a fivefold or greater elevation above the upper
      limit of normal in creatine kinase (CK) levels with a muscle/brain (MB) fraction
      of < 5% in patients with a known risk factor for this disorder. During the 12
      years from 1989 to 2001, 69 patients met our study criteria. The most common
      causes were infection and trauma. Of the 69 patients, 32% developed acute renal
      failure (ARF) which is defined as an elevation in creatinine to 2.0 mg/dL or
      greater. Although all patients received intravenous fluids (IVF), many did not
      receive other treatments such as sodium bicarbonate, furosemide, and mannitol.
      There was no significant difference in peak serum creatinine or creatine kinase
      (CK) levels between smokers and non-smokers. Eleven of the 13 patients required
      dialysis (p = 0.031), 17 of the 22 had ARF (p = 0.026), and all nine patients who
      died were smokers (p = 0.008). Thus, smokers with rhabdomyolysis have higher
      morbidity and mortality rates than non-smokers.

PMID- 14650901
TI  - Radiofrequency maze ablation for atrial fibrillation in a patient undergoing
      atrial septal defect repair.
AB  - Chronic atrial fibrillation affects over 2.2 million people and is associated
      with complications including heart failure, stroke, and exercise intolerance.
      Since drug therapy and cardioversion have been only partially successful in
      restoring sinus rhythm, surgical procedures were developed for medically
      refractory atrial fibrillation (1). We report a case of successful left atrial
      radiofrequency ablation for chronic atrial fibrillation in a patient who had a
      large secundum atrial septal defect.

PMID- 14650902
TI  - Case report: bacterial tracheitis in an adult female.
AB  - Bacterial tracheitis is an extremely rare entity, long considered to be a disease
      of pediatrics. However, cases continue to be reported among adult patients. We
      present the case of a 19-year-old female patient who presented to our Emergency
      Department (ED) with bacterial tracheitis. Other adult cases of bacterial
      tracheitis as reported in the literature from 1981 to the present are discussed.

PMID- 14650903
TI  - Mediation becomes option to resolve Medicare beneficiary complaints.

PMID- 14650904
TI  - Phylogenetic and ontogenetic aspects of the basal forebrain cholinergic neurons
      and their innervation of the cerebral cortex.

PMID- 14650905
TI  - Structural determinants of the roles of acetylcholine in cerebral cortex.

PMID- 14650906
TI  - Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus.
AB  - The M1, M2 and M4 subtypes of mAChRs are the predominant receptors in the CNS.
      These receptors activate a multitude of signaling pathways important for
      modulating neuronal excitability, synaptic plasticity and feedback regulation of
      ACh release. In addition, novel functions mediated by mAChRs are currently being
      discovered. These studies are greatly facilitated by the recent development of
      subtype selective toxins and mice lacking individual mAChR genes. Studies in cell
      culture and the rodent brain demonstrate that mAChR internalization and
      intracellular trafficking is an important component of mAChR regulation.
      Characterizing mAChR intracellular trafficking could help facilitate the
      development of selective mAChR ligands. For example, a selective M1 agonist would
      cause a shift in the distribution of M1 from the cell surface to an intracellular
      distribution, while M2 and M4 would remain on the cell surface. Characterizing
      mAChR intracellular trafficking is also important for understanding the cellular
      mechanisms that regulate mAChR cell surface expression and signaling.
      Furthermore, intracellular trafficking has recently been demonstrated to play a
      role in the development of tolerance to drugs (Whistler et al., 1999; He et al.,
      2002). Because individual mAChR subtypes are novel targets for treatments of
      diseases such as Alzheimer's disease and schizophrenia, understanding the
      mechanisms that regulate mAChR signaling and intracellular trafficking following
      acute and chronic stimulation might lead to the development of rational
      strategies.

PMID- 14650907
TI  - The cholinergic innervation of the human cerebral cortex.

PMID- 14650908
TI  - Synaptic mechanisms modulated by acetylcholine in cerebral cortex.

PMID- 14650909
TI  - Functional and molecular characterization of neuronal nicotinic ACh receptors in
      rat hippocampal interneurons.

PMID- 14650910
TI  - The nicotinic acetylcholine receptor subtypes and their function in the
      hippocampus and cerebral cortex.
AB  - Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central
      nervous system and have been implicated in multiple behavioral paradigms and
      pathological conditions. Nicotinic therapeutic interventions require an extensive
      characterization of native nAChRs including mapping of their distribution and
      function in different brain regions. Here, we describe the roles played by
      different nAChRs in affecting neuronal activity in the hippocampus and cerebral
      cortex. At least three distinct functional nAChR subtypes (alpha 7, alpha 4 beta
      2, alpha 3 beta 4) can be detected in the hippocampal region, and in many
      instances a single neuron type is found to be influenced by all three nAChRs.
      Further, it became clear that GABAergic and glutamatergic inputs to the
      hippocampal interneurons are modulated via different subtypes of nAChRs. In the
      cerebral cortex, GABAergic inhibition to the layer V pyramidal neurons is
      enhanced predominantly via activation of alpha 4 beta 2 nAChR and to a minor
      extent via activation of alpha 7 nAChR. Such diversity offers pathways by which
      nicotinic drugs affect brain function.

PMID- 14650911
TI  - Studies of muscarinic neurotransmission with antimuscarinic toxins.
AB  - M1 and M4 muscarinic receptors are the most prevalent receptors for acetylcholine
      in the brain, and m1-toxin1 and m4-toxin are the most specific ligands yet found
      for their extracellular faces. Both toxins are antagonists. These toxins and
      their derivatives with biotin, radioiodine and fluorophores are useful for
      studying M1- and M4-linked neurotransmission. We have used the rat striatum for
      many studies because this tissue express exceptionally high concentrations of
      both receptors, the striatum regulates movement, and movement is altered by
      antimuscarinic agents, M1-knockout and M4-knockout. These toxins and their
      derivatives may also be used for studies of M1 and M4 receptors in the
      hippocampus and cortex.

PMID- 14650912
TI  - Hyperactivation of developing cortical circuits by acetylcholine and the ontogeny
      of abnormal cognition and emotion: findings and hypothesis.

PMID- 14650913
TI  - Synaptic mechanisms and cholinergic regulation in auditory cortex.

PMID- 14650914
TI  - Activity, modulation and role of basal forebrain cholinergic neurons innervating
      the cerebral cortex.
AB  - The basal forebrain constitutes the ventral extra-thalamic relay from the
      brainstem activating system to the cerebral cortex. Cholinergic neurons form an
      important contingent of this relay, yet represent only a portion of the
      cortically projecting and other basal forebrain neurons, which include GABAergic
      neurons. By recording, labeling and identifying neurons by their neurotransmitter
      first in vitro and then in vivo, we have determined that the cholinergic neurons
      have different physiological and pharmacological properties than other
      codistributed neurons. Cholinergic neurons discharge at higher rates during
      cortical activation than during cortical slow wave activity, and are excited by
      transmitters released from brainstem afferent neurons, including glutamate from
      reticular formation, noradrenaline (NA) from locus coeruleus, and orexin and
      histamine from posterior hypothalamus. In contrast, particular GABAergic neurons
      discharge at higher rates during cortical slow wave activity and are inhibited by
      NA. When NA is administered into the basal forebrain in naturally sleeping-waking
      rats, it elicits an increase in fast gamma EEG activity and diminution of slow
      delta EEG activity while promoting waking and eliminating slow wave sleep (SWS).
      Cholinergic neurons also have the capacity to discharge in rhythmic bursts when
      activated by particular agonists, notably neurotensin (NT). When NT is
      administered into the basal forebrain, it stimulates theta activity in addition
      to gamma while promoting waking and paradoxical sleep (PS). By increasing
      discharge and firing in rhythmic bursts in response to transmitters of the
      activating systems, cholinergic neurons can thus stimulate cortical activation
      with gamma and theta activity along with the states of waking and PS. Colocalized
      GABAergic basal forebrain neurons which are inhibited by transmitters of the
      arousal systems can oppose these actions and promote delta activity and SWS.

PMID- 14650915
TI  - Cholinergic modulation of the cortical microvascular bed.
AB  - Cortical microvessels receive a cholinergic input that originates primarily from
      basal forebrain neurons which, upon stimulation, induce significant increases in
      cortical perfusion together with a dilation of intracortical microvessels.
      Heterogeneous mAChRs have been detected in cortical microvessels with expression
      of M2 and M5 subtypes in endothelial cells, while M1 and M3, and possibly M5
      mAChR subtypes, were expressed in smooth muscle cells. Application of ACh to
      isolated and pressurized microarterioles, whether at basal tone or
      pharmacologically preconstricted, elicited only a dilation. This response was
      dependent on NO production, and was mediated by a mAChR, the pharmacology of
      which correlated best with the M5 receptor subtype. ACh afferents also project to
      intracortical neurons that synthesize NO and VIP. These correspond to distinct
      sub-populations of GABA interneurons which were found to send numerous
      projections to local microvessels. Preliminary results suggest expression of the
      VPAC1 receptor in the smooth muscle cells of intracortical arterioles, where it
      could mediate dilation as it does in cerebral arteries. Together these results
      indicate that basal forebrain ACh fibers can directly affect the cortical
      microvascular bed, but further suggest that specific populations of GABA
      interneurons could serve as a functional relay to adapt perfusion to locally
      increased neuronal activity. In confirmed cases of Alzheimer's disease, we found
      a severe ACh denervation of both cortical microvessels and NO neurons, suggesting
      that two important regulators of cortical perfusion are dysfunctional in this
      pathology.

PMID- 14650916
TI  - Acetylcholine systems and rhythmic activities during the waking--sleep cycle.
AB  - The two processes of activation in thalamocortical systems exerted by mesopontine
      cholinergic neurons are (a) a direct depolarization associated with increased
      input resistance of thalamic relay neurons, which is antagonized by muscarinic
      blockers, and (b) a disinhibition of the same neurons via hyperpolarization of
      inhibitory thalamic reticular neurons. Low-frequency (< 15 Hz) oscillations
      during slow-wave sleep, characterized by rhythmic and prolonged
      hyperpolarizations, are suppressed by brainstem cholinergic neurons and nucleus
      basalis cholinergic and GABAergic neurons projecting to thalamic reticular
      neurons. Fast rhythms (20-60 Hz) appear during the sustained depolarization of
      thalamic and neocortical neurons during brain-active states that are accompanied
      by increased release of acetylcholine (ACh) in the thalamus and cerebral cortex.
      Such fast rhythms also occur during the depolarizing phases of the slow
      oscillation (0.5-1 Hz) in non-REM sleep. Intracellular recordings of neocortical
      neurons during natural states of waking and sleep demonstrate stable and
      increased input resistance of corticocortical and corticothalamic neurons during
      the sustained depolarization in wakefulness, compared to the depolarizing phase
      of the slow oscillation in non-REM sleep. Despite the highly increased synaptic
      inputs along different afferent systems that open many conductances of cortical
      neurons during wakefulness, the increased input resistance is attributed to the
      effect of acetylcholine on cortical neurons.

PMID- 14650917
TI  - Cholinergic mechanisms mediating anesthetic induced altered states of
      consciousness.

PMID- 14650918
TI  - High acetylcholine levels set circuit dynamics for attention and encoding and low
      acetylcholine levels set dynamics for consolidation.

PMID- 14650919
TI  - Knockout and knockin mice to investigate the role of nicotinic receptors in the
      central nervous system.
AB  - The recent use of genetically engineered knockout (Ko) and knockin (Kin) animals
      for neurotransmitter receptor genes, in particular, nicotinic acetylcholine
      receptors (nAChRs) in the brain, has provided a powerful alternative to the
      classical pharmacological approach. These animal models are not only useful in
      order to reexamine and refine the results derived from pharmacological studies,
      but they do also provide a unique opportunity to determine the subunit
      composition of the nicotinic receptors which modulate various brain functions.
      Ultimately, this knowledge will be valuable in the process of designing new drugs
      that will mimic the effects of nicotine on several important pathologies or on
      smoking cessation therapies. In this review, we present recent data obtained from
      the studies of mutant animals that contributed to our understanding of the role
      and composition of nAChRs in the central nervous system (CNS). The advantages and
      pitfalls of Ko animal models will also be discussed.

PMID- 14650920
TI  - Nicotinic modulation of thalamocortical neurotransmission.

PMID- 14650921
TI  - Amyloid beta peptides and central cholinergic neurons: functional
      interrelationship and relevance to Alzheimer's disease pathology.

PMID- 14650922
TI  - Nicotinic receptor mutations in human epilepsy.

PMID- 14650923
TI  - Neurochemistry of consciousness: cholinergic pathologies in the human brain.

PMID- 14650924
TI  - Functional studies of cholinergic activity in normal and Alzheimer disease states
      by imaging technique.

PMID- 14650925
TI  - Paying attention to acetylcholine: the key to wisdom and quality of life?

PMID- 14650926
TI  - Biochips beyond DNA: technologies and applications.
AB  - Technological advances in miniaturization have found a niche in biology and
      signal the beginning of a new revolution. Most of the attention and advances have
      been made with DNA chips yet a lot of progress is being made in the use of other
      biomolecules and cells. A variety of reviews have covered only different aspects
      and technologies but leading to the shared terminology of "biochips." This review
      provides a basic introduction and an in-depth survey of the different
      technologies and applications involving the use of non-DNA molecules such as
      proteins and cells. The review focuses on microarrays and microfluidics, but also
      describes some cellular systems (studies involving patterning and sensor chips)
      and nanotechnology. The principles of each technology including parameters
      involved in biochip design and operation are outlined. A discussion of the
      different biological and biomedical applications illustrates the significance of
      biochips in biotechnology.

PMID- 14650927
TI  - Non-ribosomal peptide synthetases as technological platforms for the synthesis of
      highly modified peptide bioeffectors--Cyclosporin synthetase as a complex
      example.
AB  - Many microbial peptide secondary metabolites possess important medicinal
      properties, of which the immunosuppressant cyclosporin A is an example. The
      enormous structural and functional diversity of these low-molecular weight
      peptides is attributable to their mode of biosynthesis. Peptide secondary
      metabolites are assembled non-ribosomally by multi-functional enzymes, termed non
      ribosomal peptide synthetases. These systems consist of a multi-modular
      arrangement of the functional domains responsible for the catalysis of the
      partial reactions of peptide assembly. The extensive homology shared among NRPS
      systems allows for the generalisation of the knowledge garnered from studies of
      systems of diverse origins. In this review we shall focus the contemporary
      knowledge of non-ribosomal peptide biosynthesis on the structure and function of
      the cyclosporin biosynthetic system, with some emphasis on the re-direction of
      the biosynthetic potential of this system by combinatorial approaches.

PMID- 14650928
TI  - Horseradish peroxidase: a valuable tool in biotechnology.
AB  - Peroxidases have conquered a prominent position in biotechnology and associated
      research areas (enzymology, biochemistry, medicine, genetics, physiology, histo-
      and cytochemistry). They are one of the most extensively studied groups of
      enzymes and the literature is rich in research papers dating back from the 19th
      century. Nevertheless, peroxidases continue to be widely studied, with more than
      2000 articles already published in 2002 (according to the Institute for
      Scientific Information). The importance of peroxidases is emphasised by their
      wide distribution among living organisms and by their multiple physiological
      roles. They have been divided into three superfamilies according to their source
      and mode of action: plant peroxidases, animal peroxidases and catalases. Among
      all peroxidases, horseradish peroxidase (HRP) has received a special attention
      and will be the focus of this review. A brief description of the three super
      families is included in the first section of this review. In the second section,
      a comprehensive description of the present state of knowledge of the structure
      and catalytic action of HRP is presented. The physiological role of peroxidases
      in higher plants is described in the third section. And finally, the fourth
      section addresses the applications of peroxidases, especially HRP, in the
      environmental and health care sectors, and in the pharmaceutical, chemical and
      biotechnological industries.

PMID- 14650929
TI  - Considerations for the planning and conduct of reproducibility studies of in
      vitro diagnostic tests for infectious agents.
AB  - The US Food and Drug Administration (FDA) requires reproducibility studies for
      premarket approval of in vitro diagnostic (IVD) tests. Results of reproducibility
      studies provide an estimate of the variability of the IVD test among study sites,
      reagent lots, site operators, within a single test run, and over multiple test
      days. In planning the study, discuss the product registration strategy, including
      the intended use of the product and desired label claims, and define the study
      team. Design the sample panel according to the limit of detection or quantitation
      of the test, dynamic range of the test, FDA guidelines, sample matrix, and
      genotype. Consider legal and ethical issues for obtaining the panel parent
      specimen, such as minimizing the privacy risk and keeping promises to donors.
      During the study, review data promptly to determine invalid runs, discover trends
      in the data that may require additional operator training, ensure correct
      completion of case report forms, and resolve queries quickly. At the end of the
      study, gather the study team to review and improve processes. Use the outcome to
      set expectations of other functional areas and to provide product feedback.

PMID- 14650930
TI  - Clinical trial methods to discover and validate predictive markers for treatment
      response in cancer.
AB  - Although postoperative chemotherapy in the treatment of cancer appears to have
      reached the limit of cytoreduction, this may be due to chemotherapeutic agents
      that are administered nonselectively rather than attainment of the true limit of
      cytoreduction. Molecular profiles of tumor cells may determine tumor response to
      chemotherapy, and therefore the selective use of chemotherapy based on prediction
      will ultimately provide a cure for breast cancer. In this paper, design
      strategies for clinical trials aimed at disclosing predictive markers are
      discussed.

PMID- 14650931
TI  - Production of high-quality marketing applications: strategies for biotechnology
      companies working with contract research organizations.
AB  - Many biotechnology and pharmaceutical companies use clinical research
      organizations (CROs) to assist in the writing and preparation of clinical
      documents intended for submission to health authorities. Start-up companies often
      require the expertise of a CRO to prepare their first regulatory documents.
      Larger or more experienced companies often require CRO staff to assist at times
      of multiple simultaneous submissions. The timely production of high-quality new
      drug marketing applications requires close collaborations between the drug
      company and the CRO. The views of both CRO and industry in ensuring best
      practices are discussed.

PMID- 14650932
TI  - Use of benchmarking in the development of biopharmaceutical products.
AB  - As the pharmaceutical and biotechnology industry enters the 21st century, the
      pressure on companies to maintain the level of productivity required for
      consistent year-on-year growth is increasing. Benchmarking has become a tool for
      obtaining the information needed to support continuous improvement and gain a
      competitive advantage. During the process of benchmarking, best practices can be
      identified while giving management the ability to improve on existing performance
      in an objective, well-informed manner. When used appropriately, benchmarking
      provides a new perspective on traditional methods while enabling companies to
      monitor their performance.

PMID- 14650933
TI  - The state of biopharmaceutical manufacturing.
AB  - The manufacturing of protein-based biopharmaceuticals is done in bacterial or
      mammalian cell cultures. While bacterial cultures are inexpensive, dependable,
      and approved by regulatory authorities, many complex proteins cannot be
      manufactured this way. Complex proteins must be manufactured in mammalian cell
      cultures to produce active products. Mammalian cell culture capacity is limited
      and has slowed the delivery of necessary biopharmaceutical products to patients.
      The nature of the production capacity problem and future outlook are critically
      examined.

PMID- 14650934
TI  - Review of current authorship guidelines and the controversy regarding publication
      of clinical trial data.
AB  - Publication of clinical trial data is the final step in the scientific method and
      an important method by which pharmaceutical and biotechnology companies, i.e.,
      drug sponsors, disseminate information about their products. Because of the
      nature of large, multicenter trials, multiple investigators from many
      institutions may be considered as authors of these papers. Controversy concerning
      the rights of academic institutions and the rights of drug sponsors has been
      widely debated. This chapter summarizes the controversy and the current policies.

PMID- 14650935
TI  - Protein electrostatics: a review of the equations and methods used to model
      electrostatic equations in biomolecules--applications in biotechnology.
AB  - The molecular understanding of the initial interaction between a protein and,
      e.g., its substrate, a surface or an inhibitor is essentially an understanding of
      the role of electrostatics in intermolecular interactions. When studying
      biomolecules it is becoming increasingly evident that electrostatic interactions
      play a role in folding, conformational stability, enzyme activity and binding
      energies as well as in protein-protein interactions. In this chapter we present
      the key basic equations of electrostatics necessary to derive the equations used
      to model electrostatic interactions in biomolecules. We will also address how to
      solve such equations. This chapter is divided into two major sections. In the
      first part we will review the basic Maxwell equations of electrostatics equations
      called the Laws of Electrostatics that combined will result in the Poisson
      equation. This equation is the starting point of the Poisson-Boltzmann (PB)
      equation used to model electrostatic interactions in biomolecules. Concepts as
      electric field lines, equipotential surfaces, electrostatic energy and when can
      electrostatics be applied to study interactions between charges will be
      addressed. In the second part we will arrive at the electrostatic equations for
      dielectric media such as a protein. We will address the theory of dielectrics and
      arrive at the Poisson equation for dielectric media and at the PB equation, the
      main equation used to model electrostatic interactions in biomolecules (e.g.,
      proteins, DNA). It will be shown how to compute forces and potentials in a
      dielectric medium. In order to solve the PB equation we will present the
      continuum electrostatic models, namely the Tanford-Kirkwood and the modified
      Tandord-Kirkwood methods. Priority will be given to finding the protonation state
      of proteins prior to solving the PB equation. We also present some methods that
      can be used to map and study the electrostatic potential distribution on the
      molecular surface of proteins. The combination of graphical visualisation of the
      electrostatic fields combined with knowledge about the location of key residues
      on the protein surface allows us to envision atomic models for enzyme function.
      Finally, we exemplify the use of some of these methods on the enzymes of the
      lipase family.

PMID- 14650936
TI  - The development of supportive-care agents for patients with cancer.
AB  - As the population ages, a dramatic increase in the number of cases of cancer is
      expected and the need for supportive-care agents, those used to ameliorate some
      of the side effects of cancer or its treatment, becomes more urgent. At present,
      supportive-care products are available and new agents are being developed with
      novel mechanisms of action or modifications of existing agents that improve
      performance. Because of the urgent need for such products, efficient development
      is required to deliver useful products to patients as rapidly as possible. This
      chapter uses actual examples to illustrate the stages of drug development, phase
      I through phase 3.

PMID- 14650937
TI  - [Heart functions].

PMID- 14650938
TI  - [Single-molecule dynamics in cell communication process].

PMID- 14650939
TI  - [Method for simultaneous recording of optical and electrical signals from single
      ion channels].

PMID- 14650940
TI  - [First aid measures by bystanders at the place of accident: useful or
      dangerous?].

PMID- 14650941
TI  - Complementary therapies for cancer, more good than harm?

PMID- 14650942
TI  - [From plagues of the past to epidemics of the present].

PMID- 14650944
TI  - [First aid measures by bystanders at the place of accident. A prospective,
      epidemiologic study in the Vienna area].
AB  - The object of this prospective, epidemiological study was to determine whether
      bystanders provided necessary first aid measures in the prehospital trauma
      setting, whether they performed these measures correctly, and whether the level
      of first aid training affected the quality of first aid measures performed. Data
      were collected by means of a questionnaire, which was filled out between March
      and July 2000 for all cases attended to by the Vienna Ambulance Service. A total
      of 2812 cases were documented. The most frequent causes of trauma were falls from
      heights less than 1 meter (50%) and traffic accidents (17%). The most frequent
      injuries were injuries to the extremities (59%) and head and traumatic brain
      injuries (42%). Most patients were "moderately" or "severely" injured (69% and
      29%, respectively), but life-threatening injuries were rare (2%). Bystanders were
      present in 57% of the cases. The most frequently required first aid measures were
      "application of a dressing" and "positioning" of the patient. "Control of
      haemorrhage", "ensuring accident site safety" and "extrication" of the patient
      were less frequently required. "Clearing of the airway", "precautions against
      hypothermia" and cardio-pulmonary resuscitation were very rarely required.
      Bystanders were most frequently policemen, relatives or friends of the patient,
      and strangers. The vast majority of bystanders had no training in first aid or
      had only attended the first aid course required to attain a driving license. We
      found a clear relationship between the level of first aid training and the
      quality of first aid measures provided. It would be advisable to offer an
      increased amount of refresher courses in first aid to improve bystander trauma
      care.

PMID- 14650945
TI  - Complementary therapies in cancer patients: prevalence and patients' motives.
AB  - BACKGROUND: Data relating to the use of complementary/alternative medicine (CAM)
      in cancer patients have been published for a number of European countries. No
      recent data are available for Austria. AIM: To ascertain the extent of CAM use by
      cancer patients, what patients' motives are, what methods are used and who the
      CAM providers are. DESIGN: Self-administered questionnaire; cross-sectional
      study. PATIENTS AND METHODS: A sample of 231 cancer patients who had consulted
      the Viennese Cancer League. Chi-square and Mantel-Haenszel tests were used for
      the statistical evaluation. RESULTS: 27.3% of the cancer patients had received
      CAM therapy: 33.1% of the female and 20.5% of the male participants (p = 0.045).
      Those who were below the median of the age categories (53.8 years) had used CAM
      to a statistically higher degree (35.5% vs. 21.1%; p = 0.023). The most important
      motives were the enhancement of "nature" and the GPs' recommendation. CAM was
      administered in 44.4% of cases by the family doctor, in 39.7% by patients
      themselves, in 6.3% by a hospital doctor, in 6.3% by a lay-practitioner or "non
      medical practitioner against payment" and in 4.8% of cases by a practising
      oncologist. CONCLUSION: From the high percentage of patients who use CAM without
      consulting a physician or who follow the advice of others, it would seem highly
      probable that conventional and complementary methods are rarely effectively
      coordinated. To rectify this we conclude that oncologists and GPs should have a
      basic knowledge of CAM and address the issue when counselling their cancer
      patients.

PMID- 14650943
TI  - Tuberculosis and HIV disease: two decades of a dual epidemic.
AB  - The HIV epidemic is currently in its third decade without any sign of abating.
      Tuberculosis (TB) is responsible for a third of all AIDS deaths, 99% of which
      occur in developing countries. The two epidemics fuel each other, together making
      up the leading infectious causes of mortality worldwide. Tuberculosis-HIV
      coinfection presents special diagnostic and therapeutic challenges and
      constitutes an immense burden on the health care systems of heavily infected
      countries. Despite major gains that have been made in the past two decades,
      important questions still remain. To cope with the challenge of TB-HIV
      coinfection, further research in the design of diagnostic tests for tuberculosis,
      detection of drug resistant Mycobacterium tuberculosis strains in HIV-positive
      people, as well as development of more effective therapeutic agents and vaccines
      are urgently needed. It has become evident that this dual epidemic will persist
      unless comprehensive measures are instituted through the provision of sufficient
      funding in addition to expanding and strengthening current control strategies
      adopted by governments and international organizations.

PMID- 14650946
TI  - Safety of a combined strength and endurance training using neuromuscular
      electrical stimulation of thigh muscles in patients with heart failure and
      bipolar sensing cardiac pacemakers.
AB  - Neuromuscular electrical stimulation (NMES) is an effective and non-strenuous
      therapy to enhance the strength and endurance capacity of the skeletal muscles in
      patients with severe chronic heart failure. NMES in patients with pacemakers is
      controversial because potential electromagnetic interference may result in
      pacemaker malfunction. Therefore, such patients are in general excluded from
      NMES. The aim of this pilot study was to evaluate the safety of a combined NMES
      protocol to increase strength and endurance capacity of the skeletal muscles in
      patients with heart failure and implanted pacemakers. Seven patients with chronic
      heart failure and implanted cardiac pacemakers with bipolar sensing leads
      received NMES treatment of thigh muscles, using a combined protocol comprising
      biphasic, symmetric, rectangular constant current impulses at different
      frequencies (8-50 Hz), pulse width up to 60 s (8 Hz), 4 s (15 Hz), 4 s (30 Hz),
      and 6 s (50 Hz), and amplitudes up to +/- 100 mA (all frequencies) applied to
      both knee extensor and flexor muscles via surface electrodes (8 x 13 cm each).
      Acute electromagnetic interference during a safety procedure (telemetric
      monitoring) before therapeutic NMES application was not observed in any of the
      patients. The 7 patients received during 20 therapeutic NMES sessions a total of
      23,380 on-phases, comprising 2194.08 x 10(3) biphasic electrical pulses, without
      adverse events. Heart rate monitoring during stimulation and pacemaker
      interrogation revealed no abnormalities. NMES treatment of thigh muscles using a
      combined NMES protocol to enhance strength and endurance capacity appears to be
      safe in patients with heart failure and implanted pacemakers with bipolar
      sensing, as far as the described electrode configuration and parameter range is
      applied.

PMID- 14650947
TI  - Pain and stress management in the Neonatal Intensive Care Unit--a national survey
      in Austria.
AB  - Neonates are sensitive to pain and vulnerable to both its short-term and long
      term effects. Management of analgesia is thought to be hampered by lack of
      awareness that newborns are capable of experiencing pain and by fears about
      adverse effects associated with analgesics. The purpose of this study was to
      assess current medical practice in preventive analgesia and sedation in the
      neonate throughout Austria. This report details the results of a survey in 28
      neonatal intensive care units (NICUs) in Austria. Data collection took place from
      October to December 2001. All NICUs reported the capability of newborns to
      experience and express pain and nearly all stated the possibility of pain
      affecting morbidity. Validated scores for pain assessment were used by 11% of
      NICUs, standardized protocols for analgesia existed in 75%, and 100% practiced
      non-pharmacological treatment strategies. The use of preventive measures in
      routinely performed painful procedures ranged from 8% to 96%. For example, only
      8% of NICUs prevent distress and pain prior to umbilical vessel catheterization,
      29% prior to subcutaneous injections and 46% prior to heel lancing. Nearly all
      NICUs apply analgesia before lumbar puncture and thoracic-drain placement, and
      all use analgesic and/or sedative medication in elective intubation. CONCLUSION:
      There is widespread awareness among neonatologists of the importance and effects
      of distress caused by pain in newborns. However, the necessity of providing
      sufficient analgesia is underestimated. Further information on the safety of
      analgesic drugs in neonatology is imperative.

PMID- 14650948
TI  - Women's position during labour: influence on maternal and neonatal outcome.
AB  - AIM: To assess the maternal, perineal and neonatal outcomes of an upright
      position compared with a supine position during vaginal delivery, in terms of
      defined outcome variables. METHODS: This case-control study was carried out at
      the Department of Obstetrics and Gynaecology of the University Hospital Vienna
      between 1997 and 2002. A total of 307 women who delivered in an upright position
      were enrolled in the study. Upright position was defined as free squatting and
      was also described as an alternative birth position. 307 controls, delivering in
      a supine position, were selected from the delivery database as the next parity
      matched normal spontaneous vaginal delivery. Our analysis was restricted to a
      sample of women with a gestational age > 37 weeks, a normal sized fetus and a
      pregnancy with cephalic presentation. Women with medical or obstetric risk
      factors were excluded. RESULTS: A statistically significant decrease for the use
      of medical analgesia (p = 0.0001) and oxytocin (p = 0.001) was observed in women
      using the upright birth position. The length of the first and second stages of
      labour did not significantly differ between the two groups (p > 0.05). A
      significantly lower rate of episiotomy was detected in women who delivered in an
      upright position compared with women delivering supine (p = 0.0001). The
      frequency of perineal tears, and vaginal and labial trauma did not differ between
      the two groups (p > 0.05). When analysing maternal blood loss, no significant
      differences between the two groups were found (p > 0.05). No differences in APGAR
      score < 7 at 1 and 5 minutes or cord pH < 7.1 were observed (p > 0.05).
      CONCLUSIONS: The data indicate that labouring and delivering in an upright
      position is associated with beneficial effects such as a lower rate of
      episiotomy, and a reduced use of medical analgesia and oxytocin. In our opinion,
      the best recommendation is to give low-risk maternity patients the option of
      bearing in the mode that is most comfortable for them.

PMID- 14650949
TI  - Detection of corticotropin-releasing hormone receptors R1 and R2 (CRH-R1, CRH-R2)
      using fluorescence immunohistochemistry in the myometrium of women delivering
      preterm or at term.
AB  - OBJECTIVE: To determine differences in expression of corticotropin-releasing
      hormone receptors R1 and R2 in the myometrium of women delivering preterm or at
      term, with or without labor. MATERIAL AND METHODS: Small pieces of myometrial
      smooth muscle were taken from forty patients undergoing caesarian section. One
      sample each was taken from all preterm and term patients, with and without labor.
      Antibodies against CRH-R1/2 and CRH-R2 were used for localization by conventional
      fluorescence immunohistochemistry. The evaluation of staining was based on
      examination of the entire histologic section by three independent observers.
      RESULTS: In women at term, CRH-R2 levels were elevated before labor and decreased
      with the onset of labor. In eight of 10 term samples from women in labor, no
      staining was detected. In preterm patients we found no difference in CRH-R2
      staining between women with and without labor. The intensity of staining for CRH
      R1/2 was generally uniform in all four groups. CONCLUSION: The high level of CRH
      R2 expression in term patients without labor, together with the subsequent
      decrease of CRH-R2 in the myometrium during progression of labor, is consistent
      with the possibility that CRH may have autocrine/paracrine effects on myometrial
      contractility in the lower segment of the uterus.

PMID- 14650950
TI  - Misdiagnosis of pulmonary embolism in patients with allergic reaction--the
      importance of prior probability of disease.
AB  - Because pulmonary embolism (PE) and its treatment carry substantial risk of
      morbidity and mortality, accurate diagnosis is essential. We report two cases
      with allergic reactions, in which PE was suggested by routine ECG and D-dimer
      elevation and strengthened by spiral CT. Therapy with low-molecular-weight
      heparin was initiated and long-term anticoagulation was considered. As their
      histories did not reveal any predisposing factor to PE, the cases were re
      evaluated. Elevation of D-dimer was now attributed to allergic reaction, ECG
      abnormalities were considered as constitutional, and findings from spiral CT
      attributed to breathing artifacts and partial-volume effects. The diagnosis of PE
      was therefore rejected and anticoagulant treatment discontinued without sequelae.
      These cases show the importance of determining clinical probability before
      ordering further diagnostic tests and critical interpretation of test results
      suggestive of PE, based on prior probability of the disease.

PMID- 14650951
TI  - Acute colonic pseudo-obstruction (Ogilvie's-syndrome) and pneumatosis
      intestinalis in a kidney recipient patient.
AB  - Acute colonic pseudo-obstruction (Ogilvie's syndrome) is a clinical entity
      characterized by massive nontoxic dilatation of the colon in the absence of
      mechanical obstruction and is associated with increased morbidity and mortality
      in the immunosuppressed patient. We present a case of a kidney transplant
      recipient developing a life-threatening condition with acute colonic pseudo
      obstruction associated with radiologic findings of a linear pneumatosis
      intestinalis (PI). Urgent laparotomy and resection of the dilated cecum, colon
      ascendens and transversum was performed because of bowel necrosis with multiple
      serosal defects. Stool cultures and special stains for microorganisms were all
      negative, and there was no evidence for viral or fungal infection. The patient
      was discharged 31 days after transplantation with normal renal function. In
      conclusion, this steroid-induced ileus (pseudo-obstruction) is a potentially
      malignant early form of colonic dysmotility rarely reported in transplant
      recipients. Awareness and early recognition of the condition are critical for a
      successful outcome. Colonoscopic decompression can achieve reversal of colonic
      dilatation in most cases, but in some patients prophylactic laparotomy is
      indicated for prevention of the catastrophic consequences of perforation.

PMID- 14650953
TI  - [Chemotherapy for esophageal cancer].
AB  - Esophageal cancer is supposed to be more sensitive to chemotherapy compared to
      other gastrointestinal cancers. Since cisplatin (CDDP) was developed, it has
      become a key drug for combined chemotherapy. At present, the combination of CDDP
      and 5-fluorouracil (5-FU) is the standard regimen for the treatment of esophageal
      carcinoma. Nedaplatin (CDGP) and paclitaxel (TXL) have shown favorable results
      either as a single agent or in combination with CDDP. Comparisons of drug
      efficacy between these new regimens and CDDP/5-FU in more cases has yet to be
      carried out. However, since esophageal cancer can hardly be cured by definitive
      chemotherapy alone, chemotherapy plays an important role in the multimodality
      therapy for esophageal cancer. The results of definitive chemoradiotherapy for
      advanced esophageal cancer has recently improved. The efficacy of preoperative
      (neoadjuvant) chemoradiotherapy in terms of survival benefit still remains
      controversial according to a meta-analysis of large-scale, randomized controlled
      trials (RCTs) when compared with surgery alone. A RCT completed by the Japan
      Clinical Oncology Group (JCOG) demonstrated the prognostic benefit of
      postoperative adjuvant chemotherapy for disease-free survival in comparison to
      surgery alone. Another RCT by JCOG has been conducted to clarify whether
      preoperative or postoperative chemotherapy may have a prognostic benefit in
      patients who undergo an esophagectomy.

PMID- 14650952
TI  - [Current screening for molecular target therapy of cancer].
AB  - Recent progress in molecular biology and cancer biology has revealed that many
      molecules, which are heavily involved in the un-limited growth, anti-apoptotic
      effects and invasion of tumors, would be targets of cancer therapy. Part of the
      drugs which inhibit these molecules have shown clinical response as well as
      clinical benefits. In this review article, the summary of mechanism based drug
      screening for cancer as well as recent status of new molecular target drugs for
      cancer, are described.

PMID- 14650954
TI  - [Chemotherapy for gastric cancer].
AB  - 5-FU has been a key chemotherapeutic agent in the treatment of advanced or
      recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical
      modulation or combined chemotherapy has been developed. Although several phase
      III studies have been reported in 1990's, a standard chemotherapeutic regimen has
      not been established worldwide. Recently, newly developed anticancer agents such
      as CPT-11, TS-1, Paclitaxel, or Docetaxel can be clinically used for advanced
      gastric cancer either single agent or in combination that may further improve the
      quality of life and prolong the survival of patients with gastric cancer. In
      Japan, postoperative adjuvant chemotherapy has been actively developed to enhance
      survival benefit of surgery for patients with gastric cancer. There were a few
      positive single randomized controlled study showing benefit of adjuvant
      chemotherapy with a high evidence level. However, all reports of meta-analysis of
      adjuvant chemotherapy for gastric cancer indicated the survival benefit of
      adjuvant chemotherapy. At present, a nation-wide randomized controlled study in
      the postoperative adjuvant setting for gastric cancer using TS-1 (ACTS-GC) is
      under way that may clarify the effect of postoperative adjuvant chemotherapy in
      gastric cancer.

PMID- 14650955
TI  - [Chemotherapy for colorectal carcinoma].
AB  - 5-fluorouracil (5-FU) plus leucovorin (LV) therapy is the most widely used
      regimen with a high evidence as the first-line treatment for advanced colorectal
      cancer (CRC), as well as CPT-11 as the second-line. Recently, it is reported in
      several randomized prospective studies that convenient oral combination of UFT
      and LV has equal efficacy and less adverse effect. Intrahepatic arterial infusion
      (IHA) therapy shows high response rate in the treatment of liver metastasis.
      Survival benefit of IHA has to be disclosed by further clinical trials.
      Prospective studies showed that 6 months' administration of 5-FU and LV after
      curative resection of Dukes' C CRC contributes to a patients' better survival.

PMID- 14650957
TI  - [Chemotherapy for pancreatic cancer].
AB  - Pancreatic cancer has one of the worst prognosis of any malignant disease. The
      National Registry of Japan Pancreas Society has reported that only 13% of
      patients achieve 5 years survival after surgical resection. The vast majority of
      patients present with metastatic or unresectable disease. Gemcitabine (GEM) has
      replaced 5-fluorouracil (5-FU)-based chemotherapy as the standard of care. GEM
      first generated improvements in symptom control and survival in advanced disease,
      spurring further research. For locally advanced disease, most recent studies have
      incorporated GEM into combined-modality therapy. However, subsequent trials have
      not demonstrated that combinations of other agents with GEM extend clinical
      benefits yet. Similarly, in surgically resectable disease, current trials are
      incorporating GEM into adjuvant therapy. According to several clinical trials it
      has been demonstrated that improvements in locoregional control and survival may
      be achieved when chemotherapy using 5-FU is added to radiation for locally
      advanced pancreatic cancer. The new regimen for locally advanced disease has
      demonstrated that the better outcome is expected by chemoradiation therapy with 5
      FU followed by GEM treatment. Furthermore, one of the patients showed the
      significant regression of pancreas tumor, resulting in the successful surgical
      resection. In order to develop chemotherapy for pancreatic cancer, we are
      analyzing mRNA expression of pancreas cancer cell lines and examined their
      resistant against to GEM. One of the genes is demonstrated to be a responsible
      for drug sensitivity by clustering analysis.

PMID- 14650956
TI  - [The chemotherapy for hepatocellular carcinoma].
AB  - For the difficulty of the giving sufficient dose because of the poor liver
      function and low sensitivity for the anti-cancer agents, the chemotherapy may not
      play a central role for the hepatocellular carcinoma (HCC) patients with liver
      cirrhosis. However, the chemotherapy must be the one of important possibility as
      a multimodal treatment for the advanced HCC, for which hepatic resection, TAE and
      other general therapy would not be effective. The intraarterial perfusion
      chemotherapy is common as a chemotherapy for HCC and it is not difficult to
      maintain; the effective rate is not sufficient. Recently, the combination therapy
      with subcutaneous IFN-alpha and intraarterial 5-FU showed a outstanding effective
      rate for intractable HCC with Vp3. For the further advance of the HCC treatment
      and prognosis, this therapy might be the promising treatment modality and
      expected of the development.

PMID- 14650958
TI  - [Autoimmune phenomena during interferon-alpha therapy for hematopoietic
      disorders].
AB  - The development of various kinds of autoimmune disease as a result of interferon
      alpha (IFN-alpha) therapy has been reported among chronic myeloproliferative
      disorders(CMPD) including chronic myeloid leukemia(CML). Therefore, we
      investigated the frequency of autoimmune disorders in 33 patients with
      hematopoietic diseases treated with IFN-alpha in our department. Thirty-three
      patients (12 females, 21 males) included cases of CML (n = 23), essential
      thrombocythemia (ET) (n = 1), multiple myeloma (n = 8), and hypereosinophilic
      syndrome (HES) (n = 1). Autoantibodies (ANA, dsDNA, and RAPA), thyroid grand
      functions, and coagulant functions were examined. Twenty-five out of 33 patients
      were treated with natural IFN-alpha, and 8 patients were treated with recombinant
      IFN-alpha 2b (rIFN alpha-2b). Three patients were treated with IFN and anticancer
      agents. Antinuclear antibodies were detected in 2 of 33 patients. RAPA and anti
      thyroglobulin antibody became positive in 3 and 4 patients, respectively. Ten
      patients showed low serum levels of either free T3 and/or free T4. However, none
      of them showed any clinical symptoms for developing autoimmune diseases. In
      addition, circulating anticoagulant antibodies were detected in 3 of 23 patients
      with CML treated with rIFN alpha-2b, but in no cases treated with natural IFN
      alpha. Although none of the patients developed autoimmune diseases, we concluded
      that patients receiving IFN therapy should be carefully monitored for clinical
      signs and symptoms of autoimmune disorders.

PMID- 14650959
TI  - [Effects of docetaxel dosage in combination chemotherapy with carboplatin against
      advanced non-small cell lung cancer].
AB  - We retrospectively analyzed the effects of dosages of docetaxel (DOC) in
      combination chemotherapy with carboplatin (CBDCA) against advanced non-small cell
      lung cancer (NSCLC). Twenty-three cases of previously untreated NSCLC (stage III
      and IV, performance status: 0-1) that were pathologically or cytologically
      confirmed were divided into 2 groups (DOC-60, DOC-70) based on their received DOC
      doses (60 and 70 mg/m2, respectively). Both groups had similar patient
      characteristics and received similar treatment except for their DOC doses.
      Although not statistically significant, the response rates after the completion
      of whole cycles of the treatment (mean: 4 cycles) were 18.2% in DOC-60 and 41.6%
      in DOC-70. Leukocytopenia, neutropenia and anemia were observed similarly in both
      groups. However, while thrombocytopenia was not observed in DOC-70, it was found
      in 36.4% of the cases in DOC-60. In combination chemotherapy with carboplatin
      against advanced NSCLC, the use of DOC at 70 mg/m2 was rather protective against
      thrombocytopenia, keeping the response equivalent or possibly superior to that
      obtained in the patients treated with DOC at 60 mg/m2.

PMID- 14650960
TI  - [Non-platinum induction chemotherapy for stage III non-small cell lung cancer].
AB  - We conducted combination chemotherapy with gemcitabine (GEM) and paclitaxel (TXL)
      for stage III non-small cell lung cancer. The chemotherapy schedule consisted of
      GEM 800 mg/m2 and TXL 70 mg/m2 once a week for 6 consecutive weeks. The patients
      were 7 males and 3 females with a median age of 66 years. There were 5
      adenocarcinomas and 5 squamous cell carcinomas, 7 stage IIIA and 3 IIIB. Eight
      patients completed 6 cycles of planned administration. Of 9 patients who were
      evaluable for response, 6 patients achieved PR (66.7%), 2 patients had SD, and 1
      patient had PD. The cancers were resectable in 7 out of 9 patients, and were
      resected completely in 5 patients. Grade 3 anemia and leucopenia were observed in
      1 patient and 2 patients, respectively, but they were mild. In our experience, a
      non-platinum weekly regimen with GEM and TXL is well tolerated and effective,
      which suggests the possibility of induction chemotherapy and outpatient
      treatment.

PMID- 14650961
TI  - [Weekly docetaxel therapy is useful for gastric carcinoma as a second-line
      chemotherapy].
AB  - In the present study, we demonstrate the results of weekly administered docetaxel
      treatments as a second-line chemotherapy after TS-1 treatment in 4 gastric cancer
      patients. Twenty-five mg/m2 of docetaxel was administered once a week for 3 weeks
      followed by a 1-week rest period as one cycle. The treatment was continued for 2
      to 16 weeks. In case 1, a 60% reduction of the primary tumor was observed for 20
      weeks. In cases 2 and 3, the decrease of tumor marker was observed. In one case,
      progression of the tumor was observed and the treatment was not performed. As for
      adverse effects, no hematological toxicity was observed; however, in one case,
      grade 2 hair loss, pleural effusion and grade 2 nail changes were observed. These
      results indicate that the weekly docetaxel therapy is useful for gastric
      carcinoma patients, as it reduces the hematologic toxicities and improves the
      quality of life of the patients in the outpatient setting.

PMID- 14650962
TI  - [Evaluation of TS-1 combined with cisplatin for neoadjuvant chemotherapy in
      patients with advanced gastric cancer].
AB  - We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with TS-1
      and cisplatin (CDDP) for advanced gastric cancer patients. Since October 2000, 37
      patients with far advanced or non-curative resectable gastric cancer received
      NAC, together with TS-1 and CDDP after informed consent was obtained. TS-1 (80
      mg/m2/day) was administrated for 21 consecutive days followed by 14 days rest as
      one course, and CDDP (50 mg/m2) was infused over 2 hours on day 8. After at least
      2 courses of treatment, the patients underwent gastrectomy with lymphadenectomy.
      The median number of courses administered was 3 (range 2-7), and 6 cases were
      treated on an outpatient basis only. The overall response rate was 62.2% (no CR,
      but 23 PR), and the individual response rates were 67.6% for the primary lesion,
      90.5% for lymph node metastasis including para-aortic region, 50.0% for liver
      metastasis and 14.3% for peritoneal dissemination, respectively. Toxicities were
      generally mild, no treatment-related death and no serious adverse reactions were
      observed. There were only 2 grade 4 anemia (5.4%), and leucopenia, neutropenia,
      anemia, thrombocytopenia of grade 3 were observed in one (2.7%), 3 (8.1%), 6
      (16.2%), and 2 (5.4%) patients respectively at hematological toxicity. Appetite
      loss and diarrhea of grade 3 were observed in only one (2.7%) patient at
      nonhematological toxicity. Twenty-four cases had undergone surgical treatment,
      and resection was performed in all cases. Seventeen of the 24 (70.8%) patients
      underwent curative resection. There was no major morbidity following surgery. The
      patients were favorable both for operation time (229 min) and bleeding volume
      (365 ml). The mean duration of hospitalization after surgery was 23.5 days and
      the only complications were one leakage, ileus and 2 pancreatitis. Two-year
      survival rate was 46.8% and MST was 523 days. In conclusion, a combination of TS
      1 and CDDP for NAC appears to be an effective treatment modality for far advanced
      gastric cancer patients in view of toxicities, antitumor effects and QOL of the
      patients.

PMID- 14650963
TI  - [A case of a 91-year-old woman with maxillary sinus carcinoma who achieved a
      complete response to chemoradiotherapy with intra-arterial administration of
      docetaxel].
AB  - We treated a 91-year-old woman with advanced maxillary sinus carcinoma who
      achieved a complete response to chemoradiotherapy with intra-arterial
      administration of docetaxel. She received local irradiation with a total dose of
      50 grays along with concomitant intramaxillary arterial infusion of docetaxel
      with a total dose of 80 mg. After treatment, pathological examination of a biopsy
      specimen from the maxillary sinus revealed no residual tumor, and a posttreatment
      CT scan showed no tumor. Twenty one months after chemoradiotherapy, she had no
      recurrence and no metastasis. We conclude that chemoradiotherapy using
      intramaxillary infusion with docetaxel would be useful for maxillary sinus
      squamous cell carcinoma.

PMID- 14650964
TI  - [A case of lymph node metastasis after total laryngectomy successfully treated
      with chemoradiotherapy with TS-1].
AB  - A patient with advanced recurrent laryngeal cancer complicated with cervical
      lymph node metastasis was successfully treated with chemoradiotherapy with an
      oral anticancer drug, TS-1. TS-1 was administered at a dose of 120 mg/day. One
      course consisted of consecutive administration of TS-1 for 28 days and withdrawal
      for 14 days. During chemotherapy, the patient received concomitant radiotherapy
      (60 Gy). At the end of 2 courses, a partial response of the neck metastasis was
      achieved.

PMID- 14650965
TI  - [Resection of esophageal cancer infiltrating the left main bronchus following
      complete response to preoperative radiochemotherapy--a case report].
AB  - We report a case of esophageal cancer infiltrating the left main bronchus in
      which radical esophagectomy with clear surgical margins could be performed after
      preoperative radiochemotherapy. The patient was a 57-year-old man, who was found
      to have esophageal squamous cell carcinoma of the middle thoracic esophagus
      during a work-up of dysphagia. Bronchoscopy revealed an elevated region
      protruding into the lumen of the left main bronchus. After radiochemotherapy
      (liniac irradiation + low-dose FP therapy), the esophageal and bronchial lesion
      became smaller. The case was evaluated as a clinically complete response.
      Bronchoscopic ultrasonography showed a clear boundary between the membranous
      portion of the trachea and the esophageal wall. Based on these findings, the
      lesion was considered resectable and radical surgery, including 3-field lymph
      node dissection, was performed. The resected esophageal specimen had residual
      cancer cells in the muscularis propria covered with normal mucosa. However, the
      patient is currently healthy with no evidence of disease. The indication for
      surgical resection in cases of esophageal cancer with contiguous spread, and a
      good response to preoperative radiochemotherapy, is controversial. It is
      necessary to verify the effectiveness of surgical resection, as a secondary
      treatment, by accumulating data on cases such as the present one.

PMID- 14650966
TI  - [Preliminary evaluation of chemotherapy with docetaxel, 5-FU, CDDP for recurrent
      esophageal cancer--a pilot study].
AB  - A pilot study has been conducted since January 2002 to investigate whether
      chemotherapy with docetaxel, 5-FU, CDDP could be an effective regimen for
      recurrent esophageal cancer. Ten patients with recurrent esophageal cancer were
      treated with the combination of docetaxel 60 mg/m2 (day 1), CDDP 10 mg/body (days
      1-5) and 5-FU 500 mg/body (days 1-5) at intervals of 2-3 weeks. All patients had
      undergone surgery, had a recurrent tumor and had already been treated with chemo
      radiotherapy or chemotherapy with CDDP + 5-FU. Response evaluation in 10 patients
      with measurable disease: partial response 4 patients, stable disease 2 patients
      and progressive disease 4 patients. The main NCI-CT grade 3/4 toxicity was
      leukopenia (8/10). Mild to moderate nausea (> or = grade 2) occurred in 3/10
      patients.

PMID- 14650967
TI  - [A case of advanced thymic cancer successfully treated with neoadjuvant intra
      arterial infusion chemotherapy].
AB  - We report the case of a 68-year-old man with advanced thymic cancer who was
      diagnosed as having squamous cell carcinoma by percutaneous needle biopsy. The CT
      scan showed pre-cardiac and pulmonary invasion, therefore the tumor was
      classified as Masaoka's stage III. Induction systemic chemotherapy consisting of
      CDDP (70 mg/m2, day 1), ADM (40 mg/m2, day 1) and ETP (70 mg/m2, day 1-3) was
      performed for the purpose of reducing the tumor size; however, the tumor's size
      did not shrink. Therefore, second line chemotherapy combined with selective intra
      arterial infusion chemotherapy and systemic chemotherapy consisting of CDDP (70
      mg/m2, day 1; intra-arterial), ADM (30 mg/m2, day 1; intra-arterial), VCR (0.5
      mg/m2, day 3; systemic) and CPA (500 mg/m2, day 3; systemic) was performed. After
      this treatment, the tumor was reduced in size, and an extended thymectomy was
      subsequently performed. The histological diagnosis of the resected tumor was
      squamous cell carcinoma. Examination of the resected tumor revealed extensive
      necrosis and only a few cancer cells. These results show that intra-arterial
      infusion chemotherapy may be effective for local control of advanced thymic
      cancer.

PMID- 14650968
TI  - [A case of advanced cancer with liver metastasis and paraaortic lymph node
      metastasis responding remarkably to combination chemotherapy of low-dose CDDP, 5
      FU and CPT-11].
AB  - A 57-year-old male patient with upper epigastric discomfort was introduced to our
      hospital from another clinic because of gastric cancer. Several examinations
      showed massive liver metastasis and paraaortic lymph node metastasis from Type-3
      gastric cancer beneath the posterior wall of the pyloric antrum. First we tried
      infusion of CDDP (10 mg/day for days 1-5 and 8-12) and continuous infusion of 5
      FU (500 mg/day for 14 days). Concurrently, we added infusion of CPT-11 (80 mg/day
      on days 1,8). After 3 courses of chemotherapy, the tumor had decreased remarkably
      in size. Moreover, liver metastasis and paraaortic lymph node metastasis had
      vanished. This regimen thus appears to be effective for advanced gastric
      carcinoma.

PMID- 14650969
TI  - [A case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU
      and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP].
AB  - We report a case of advanced gastric cancer that responded to docetaxel with low
      dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to
      M-FLP. A 52-year-old male was diagnosed with type 3 gastric cancer of angulus
      (poorly differentiated adenocarcinoma) with left neck, Virchow, mediastinal and
      abdominal lymph nodes metastases. The patient was treated with 5 courses of M-FLP
      (MTX + 5-FU + LV + CDDP), and the effect of this therapy was PR, but the tumor
      was chemoresistant to the sixth course of this therapy. After 7 courses of M-FLP,
      docetaxel (TXT) with low-dose FP (5-FU + CDDP) was administered to the patient as
      second-line chemotherapy. After 2 courses of TXT with low-dose FP, the gastric
      cancer and metastatic lymph nodes were remarkably reduced and the effect of this
      therapy was PR. The toxic events were anemia (grade 2) and leukopenia (grade 3),
      which were treated with G-CSF. CDDP and 5-FU based regimens are considered as the
      first-line chemotherapy for metastatic advanced gastric cancer in Japan; however,
      a second-line chemotherapy has not been established. As in this case, a TXT based
      regimen is effective and well tolerated therapy as a second-line chemotherapy for
      metastatic gastric cancer after prior exposure to CDDP and 5-FU.

PMID- 14650970
TI  - [A case of gastric carcinoma with multiple skin, bone, and bilateral ovary
      metastasis; effective treatment by chemotherapy].
AB  - A 40-year-old female visited our hospital with general malaise. She was diagnosed
      with gastric carcinoma with multiple skin, bone, and bilateral ovary metastases.
      Chemotherapy with 5-FU (1,000 mg/w) and cisplatin (10 mg/w) was performed in the
      outpatient clinic. Two years after the initial diagnosis, CEA was elevated. She
      then was given chemotherapy of CPT-11 (40 mg/w) in the outpatient clinic after 1
      cycle of combined chemotherapy of CPT-11 and cisplatin. She died 38 months after
      the initial diagnosis. Weekly 5-FU/CDDP or low-dose CPT-11 appear to be effective
      for such a gastric carcinoma with systemic metastases without impairing quality
      of life.

PMID- 14650971
TI  - [A case of effective response to TS-1 of inoperable gastric cancer, in the course
      of chemotherapy for malignant lymphoma].
AB  - We encountered a case of effective response to TS-1 of inoperable gastric cancer,
      in the course of chemotherapy for malignant lymphoma. A 78-year-old man, in the
      course of chemotherapy for malignant lymphoma, complained of appetite loss. A
      biopsy from gastric endoscopy indicated gastric carcinoma. This was diagnosed as
      inoperable gastric cancer, and gastro-jejunostomy was performed. After
      administration of TS-1 orally for 4 courses, it was observed to be effective with
      no severe adverse events.

PMID- 14650972
TI  - [Effective use of combination chemotherapy with paclitaxel and 5-fluorouracil in
      a case of non-resectable advanced gastric cancer].
AB  - The patient was a 67-year-old man who had gastric cancer located in the posterior
      wall of the stomach and who underwent surgery on June 27, 2001. The operative
      finding was carcinomatous peritonitis in which the primary lesion was considered
      to be surgically unresectable. Therefore, only a probe laparotomy was performed.
      Under full informed consent, we performed combination chemotherapy with
      paclitaxel and 5-fluorouracil, 5-fluorouracil (600 mg/m2/day) was infused
      continuously for 120-hours (day 1-5) on administration and paclitaxel (60 mg/m2)
      was infused for 1.5 hours after premedication at day 8, 15 and 22 on an
      outpatient basis. After 2 courses of the chemotherapy, the tumor markers were
      reduced remarkably, ascites had completely disappeared, and abdominal lymph nodes
      had decreased. No serious adverse event was observed and the patient maintained
      good QOL throughout the treatment.

PMID- 14650973
TI  - [A case of multiple hepatic metastases from colorectal cancer effectively treated
      by arterial infusion therapy with Leucovorin/5-FU].
AB  - We report a patient with multiple hepatic metastases from colorectal cancer
      effectively treated by hepatic arterial infusion therapy (5-FU/LV therapy). The
      patient was a 55-year-old man with sigmoid colon cancer and multiple hepatic
      metastases, 5 cm in diameter, in both lobes of the liver. First, we locally
      controlled the sigmoid colon cancer by sigmoid colectomy (with D3 lymph node
      dissection). After resection of the primary cancer lesions and dissection of the
      lymph nodes, we treated the patient by systemically administering 4 courses of
      Leucovorin/5-FU (once weekly for 6 weeks per course) from a port-catheter system
      during hospital stay and in the outpatient clinic after hospital discharge.
      Assessment of therapeutic effects by CT showed CR in the patient. CEA levels,
      which were abnormal before and after surgery, decreased to normal at the end of
      chemotherapy. After 1 year, neither CT evidence of tumor enlargement in the liver
      nor re-increase in CEA levels has been noted. Although the patient experienced
      side effects such as pigmentation, grade 1 loss of appetite, and leukopenia, he
      was able to maintain his QOL in the absence of severe side effects.

PMID- 14650974
TI  - [A case of advanced breast cancer with multiple lung, bone and lymph node
      metastases successfully treated with 5'-DFUR alone].
AB  - A 78-year-old female patient with locally advanced breast cancer, bleeding from a
      deep ulcer, and with multiple bone, lung and distant lymph node metastases was
      successfully treated with 5'-DFUR alone. She was at first treated with docetaxel
      + 5'-deoxy-5-fluorouridine (5'-DFUR) + tamoxifen, but they were discontinued
      because of deep venous thrombosis. She underwent simple mastectomy due to
      periodically recurring bleeding and infection. After administration of 5'-DFUR
      alone, a decrease of abnormal accumulation on a bone scintigram was obtained in
      10 months, the lung metastases were diagnosed as being in complete remission (CR)
      at 11 months and the lymph node metastases were diagnosed as being in CR at 14
      months. These states have continued to the present. The administration of 5'-DFUR
      alone is suitable for tumor dormancy in some cases.

PMID- 14650975
TI  - [Marked reduction of BCR-ABL fusion chromosome positive cells with interferon
      therapy combined with short-term imatinib in chronic myelogenous leukemia].
AB  - A 71-year-old man with chronic myelogenous leukemia received interferon therapy
      for 21 months, but did not have complete cytogenetic response. Imatinib was then
      added to the former therapy. Imatinib was prescribed for only 12 days and
      discontinued because of severe erythema. Since then, however, marked reduction of
      bcr-abl fusion chromosome positive cells was observed, and this state has been
      maintained to the present day even though treatment has consisted only of
      interferon. we discuss efficacy of the combined therapy, composed of interferon
      and imatinib, for chronic myelogenous leukemia and other bcr-abl fusion
      chromosome positive diseases.

PMID- 14650976
TI  - [Evidence-based management of chemotherapy related thrombocytopenia].
AB  - The availability of G-CSF increases the safety margin of chemotherapy use,
      especially in the management of infection. This in turn makes administration of a
      more intense regimen of chemotherapy possible. However, this improvement in
      neutropenic management could lead to an undesirable concurrent rise in
      thrombocytopenia risk due to the higher dose of chemotherapy administered.
      Although mortality from thrombocytopenia is generally quite rare, transfusions of
      platelets are often expensive and can be associated with side effects such as
      fever, hypersensitivity reaction, and occasionally infection. Therefore,
      transfusion of platelets should be performed when it is truly indicated. In
      general, the threshold for platelet transfusion is accepted as being when the
      platelet count drops below 10,000/microliter, unless there is an obvious bleeding
      lesion or other coagulation abnormality, such as DIC being identified in the
      patients. On the other hand, thrombotic microangiopathy (TMA) can also occur as a
      rare complication of the malignancy itself or from the associated cancer
      chemotherapy. The major features of TMA are thrombocytopenia and marked increases
      of destroyed erythrocytes and LDH in peripheral blood. Despite a low incidence,
      its high mortality rate makes it important for all physicians caring for cancer
      patients to be aware of it, especially in view of the ready availability of
      successful treatments (e.g., plasma exchanges). Early diagnosis of TMA in
      patients receiving chemotherapy requires special attention because some
      characteristics of TMA are often masked by common side-effects of chemotherapy
      such as bone marrow suppression. Since delay in initiation of plasma exchange
      could result in higher mortality, urgent hematology consultation should be
      obtained if TMA is ever suspected.

PMID- 14650977
TI  - Systems approach helps PA hospital improve patient safety.

PMID- 14650978
TI  - Scanning medication barcodes improves accuracy at Lehigh Valley Hospital.
AB  - Performance improvement often means doing tasks faster, but it can also involve
      increasing the accuracy of a health care process and reducing error rates. At
      Lehigh Valley Hospital in Allentown, PA, the implementation of a wireless barcode
      scanning system has increased the accuracy of nurses giving medications to
      patients, even though it has slowed them down a bit.

PMID- 14650979
TI  - Project teams produce successful turnaround for Illinois hospital.
AB  - When Jay Kreuzer was hired as president and CEO of West Suburban Health Care, it
      didn't take him long to realize the organization was headed in the wrong
      direction. The not-for-profit system, which includes a 258-bed medical center,
      was projected to end fiscal year 2001 with a loss of $19 million. Kreuzer put
      together a team that implemented an organization-wide performance improvement
      effort. In just two years the turnaround has been completed, as West Suburban
      ended fiscal year 2003 with a small surplus.

PMID- 14650980
TI  - Ohio hospitals and nursing homes improve care coordination.
AB  - Unnecessary transfers of elderly patients between the Summa Health System in
      Akron, OH, and 25 skilled nursing facilities are being reduced, thanks to better
      communication about the patients' medical histories and special needs.

PMID- 14650981
TI  - [The study on specific anti-Streptococcus mutans IgY against dental caries in
      rats].
AB  - OBJECTIVE: To investigate the effect of specific anti-streptococcus mutans IgY
      against streptococcus mutans on dental caries development in rats. METHODS: 35
      wistar rats were divided into 5 groups: group A received IgY gargle; group B
      received IgY lyophilized powder; group C received sterilized water as control;
      group D and E received egg yolk food with or without specific IgY individually.
      They were all fed with caries-inducing diet 2000#. The number of caries scores
      was counted by the procedure of Keyes'. RESULTS: There was a significant lower
      mean of caries scores in groups treated with IgY lyophilized powder and gargle.
      By treating with egg-yolk food contained specific IgY, the mean of caries scores
      decreased comparing with no treatment group. CONCLUSION: Local passive
      immunization with specific anti-streptococcus mutans IgY may be an effective way
      to prevent the development of dental caries.

PMID- 14650982
TI  - [Expression of matrix metalloproteinase-3 and tissue inhibitor metalloproteinases
      1 in regenerated rabbit bone after mandibular osteodistraction].
AB  - OBJECTIVE: To observe the expression patterns of matrix metalloproteinase-3 and
      its inhibitor, tissue inhibitor metalloproteinases (TIMP)-1, in remodeling phase
      of mandibular distraction osteogenesis. METHODS: Bilateral mandibular osteotomies
      were performed in 8 mature rabbits. The mandibles were lengthened 6 mm using a
      custom-made distractor with a rate of 1 mm/d. All animals were killed in 4 weeks
      after completion of distraction. The distracted calluses were harvested and
      processed for histology and immunohistochemistry of MMP-3 and TIMP-1. RESULTS:
      Elevated expression of both MMP-3 and TIMP-1 was found in the distracted calluses
      resulting from mandibular lengthening. Positive staining for MMP-3 was seen in
      the osteoblasts and osteocytes, and TIMP-1 was mainly localized in osteoblasts.
      CONCLUSION: MMP-3 and TIMP-1 appear to play important roles in the remodeling of
      new bone created by mandibular distraction osteogenesis.

PMID- 14650983
TI  - [The roles of Notch2-Delta signaling in the differentiation of long-term cultured
      human dental pulp cells].
AB  - OBJECTIVE: To study the roles of the Notch2-Delta signaling in the
      differentiation of dental pulp cells into odontoblasts in vitro. METHODS: A long
      term culture system was used as a model for the study of proliferation and
      differentiation of pulp cells into preodontoblasts. The expression patterns of
      Notch2 and its ligand Delta in different phases of long-term cultured dental pulp
      cells were studied by immunohistochemistry and western blotting. Furthermore, the
      effects of rhBMP-2 on the expression of Notch signaling members were studied.
      RESULTS: Notch2 and its ligand Delta expressed in all phases of dental pulp cells
      and the sites and levels of their expression changed with different phases. rhBMP
      2 could significantly up-regulated the expression of Delta in the phase of later
      cell nodule formation. CONCLUSION: This study demonstrated that Notch signaling
      pathway played roles in the differentiation of long-term cultured human dental
      pulp cells which formed nudules that were slightly mineralized and had
      ultrastructural features reminiscient of preodontoblasts, and it may be the
      mechanism that control pulpal cell's responsiveness to signaling molecules in the
      healing of wound pulp.

PMID- 14650984
TI  - [Bone induction by human periodontal ligament fibroblasts transfected with bone
      morphogenetic protein 2 gene].
AB  - OBJECTIVE: To establish human periodontal ligament fibroblasts (HPDLFs) that
      express bone morphogenetic protein 2 and observe their osteogenesis in vivo, so
      as to provide fundamental data for future study on gene therapy of periodontal
      defect treatment. METHODS: The phagemid expression vector for BMP-2 (pBK-B2) was
      transfected into HPDLFs by using Lipofect AMINE. The BMP-2 expression was
      determined by immunohistochemical ABC method. The BMP-2 gene transfected HPDLFs
      were injected into thigh muscle of nude mice under sterile condition. Specimens
      were collected in 21 days after injection and underwent normal procedures for
      fixation, decalcification, embedding, incising and staining with HE. RESULTS: The
      results demonstrated that BMP-2 protein expressed in HPDLFs after BMP-2 gene
      transfection. The HPDLFs transfected with BMP-2 gene could induce new bone
      formation at the injection site. CONCLUSION: The results indicated that BMP-2
      gene was transfected successfully and expressed efficiently in HPDLFs. The HPDLFs
      transfected with BMP-2 gene are capable of inducing new bone formation in vivo.

PMID- 14650985
TI  - [DNA sequence analysis for the promoter of pyruvate oxidase gene from
      Streptococcus oralis].
AB  - OBJECTIVE: To elucidate the molecular structure of pyruvate oxidase gene
      promoter. METHODS: The 1.30 kb fragment with promoter activity, amplified from
      upstream of Streptococcus oralis pyruvate oxidase gene (Sopox), was cloned into
      vector PBK-CMV. The positive transformed E. coli JM109 clone was selected, the
      recombinant plasmid was further identified with restriction mapping analysis. The
      positive recombinant plasmid was studied with sequence analysis. RESULTS: After
      digesting the recombinant plasmid with Hind III, 1% agarose electrophoresis
      showed 1.30 kb fragment, which was consistent with predicted size. Sequence
      analysis revealed 1,350 bp. CONCLUSION: The Sopox promoter region is sequenced.
      Further characterization of the Sopox promoter region will elucidate the
      molecular mechanism of H2O2 production of streptococcus oralis.

PMID- 14650986
TI  - [The study of peptide vaccine HDS from Streptococcus mutans glucosyltransferase].
AB  - OBJECTIVE: To investigate the antigenicity of the peptide vaccine HDS from
      Streptococcus mutans glucosyltransferase and its ability to induce protective
      immune responses in an experimental rat model of dental caries. METHODS:
      Artificial antigen HDS-KLH, peptide HDS, glycosyltransferase were injected to
      immunize rats. Measurement of the specific anti-HDS, GTF IgG or IgA concentration
      in saliva and serum were undertaken by ELISA among the experimental groups.
      Gnotobiotic rat model was developed when challenged S. mutans and a caries
      promoting diet. The jaws of the rats were selected and dyed. The Keyes caries
      score for each jaw were counted. RESULTS: The level of serum and salivary
      specific anti-HDS IgG and IgA in the group immunized by HDS-KLH was significantly
      higher than that in control group (P < 0.05). The Keyes caries score of GTF, HDS
      and HDS-KLH immunized group were significantly lower than that of control group,
      especially lower in smooth tooth surface. CONCLUSION: Artificial antigen HDS-KLH
      could induce immune response. As a peptide vaccine, HDS-KLH could reduce the
      caries incidence in experimental rat model.

PMID- 14650987
TI  - [A scanning electron microscopy study on morphological changes of Er, Cr: YSGG
      laser-cutted dental hard tissue].
AB  - OBJECTIVE: The purpose of this study was to evaluate the morphological changes of
      Er, Cr: YSGG laser irradiated dental hard tissues by scanning electron microscopy
      (SEM). METHODS: 12 freshly extracted premolars were treated with fissure bur, Er,
      Cr: YSGG laser at 4 watt, Er, Cr: YSGG laser at 6 watt, respectively, and then
      bisected transversally and longitudinally. The tooth slice were prepared with
      conventional methods and observed by SEM. RESULTS: Compared with fissure bur,
      laser treatment resulted in a rather scaly and rough surface. The sections were
      free of smear layer, with open dentinal tubules. No carbonization and thermal
      damages were observed. The laser at 6 watt appeared rougher than at 4 watt,
      occasionally caused micro-cracks. CONCLUSION: The utilizing of Er, Cr: YSGG laser
      can contribute to enhance the bond strength between restorative materials and
      dental hard tissues. It suggests that higher energy could be applied in cutting
      enamel, whereas the lower energy in dentin.

PMID- 14650988
TI  - [The pathologic basis of partial parotidectomy in parotid pleomorphic adenoma
      treatment].
AB  - OBJECTIVE: The purpose of this study was to offer pathological reasons for
      partial parotidectomy adopted in parotid pleomorphic adenoma treatment. METHODS:
      Continuous slices from 25 cases of primary parotid pleomorphic adenoma were
      carefully examined and the extra-envelope infiltration, the budding and the
      primary multi-center were measured and recorded. RESULTS: The range of extra
      envelope infiltration and budding was limited in 0.09-0.285 mm out of tumor
      capsules, which was far less than the safe boundary(1 cm) of the partial
      parotidectomy. Two cases with multi-centers were found, but all the centers were
      aggregated together and encapsulated in a united envelope. CONCLUSION: Partial
      parotid parotidectomy is a safe method and can remove the tumor completely in
      parotid plemorphic adenoma treatment.

PMID- 14650990
TI  - [Sphenozygomatic suture as a guide in the reduction of zygomatic fracture].
AB  - OBJECTIVE: To retrospectively investigate the effectiveness of sphenzygomatic
      suture as a guide in the reduction of zygomatic complex fracture. METHODS: 55
      cases of zygomatic complex fracture classified according to Zingg classification
      were treated, sphenozygomatic suture in group 1 (n = 36) was reduced first, then
      the other fracture line was reduced, in group 2 (n = 19), malar bone was reduced
      according to superficial fracture line. Patients were followed up for 4 weeks to
      3 months, aesthetic result and X-ray symmetry were observed. RESULTS: All
      patients in group 1 were restored with satisfactory facial contour, 35 cases got
      precise reduction, 5 cases in group 2 were asymmetry. CONCLUSION: During open
      reduction of complex zygomatic fracture, sphenozygomatic suture should be reduced
      at first as a guide, so as to get precise zygomatic complex reconstruction and
      normal aesthetic outcome.

PMID- 14650989
TI  - [The development and in vitro release rate determination of controlled-release
      delivery gutta-percha point containing metronidazole compound].
AB  - OBJECTIVE: To prepare the controlled-release delivery gutta-percha points
      containing metronidazole compound (CDGMC) and to determine its release rate in
      vitro. METHODS: The drug points were made by using compound drugs and gutta
      percha as a carrier, and CDGMC were prepared followed by enveloping a release
      membrane outward. The best formula was selected according to the release
      parameters of the drugs extracted in the release experiments in vitro. The CDGMC
      were placed into the extracted teeth after root canals were routinely prepared.
      The non-drug CDGMC was used as the control. The absorbency of the drugs in normal
      saline (37 degrees C, pH 7.4) was determined timely. The percentage of release
      and cumulated release of the drugs were calculated according to the
      concentrations of drugs in medium. RESULTS: The in vitro experiments showed that
      this system contained 1,880 micrograms of metronidazole and 267 micrograms of
      ciprofloxacin. The experiments in healthy single root canal showed that the drug
      release amounts around the perioapical area were metronidazole 88.54
      micrograms/ml and ciprofloxacin 9.05 micrograms/ml in 10 days. CONCLUSION: CDGMC
      can continuously release effective drug concentrations more than 10 days and
      could be considered as an ideal method for clinical application.

PMID- 14650991
TI  - [The measurement of retentive forces in mandibular complete overdenture with
      Magfit magnetic attachments].
AB  - OBJECTIVE: To evaluate the in vivo retentive forces of mandibular complete
      overdenture with Magfit attachments, as well as the relation between the location
      of magnetic attachments and the retentive forces of the denture. METHODS: 5
      patients were selected and treated with mandibular complete overdentures retained
      by Magfit EX600 and MD800 attachments. A strainometer was used to measure the
      retentive forces in anterior, central and posterior parts of the overdenture
      before and after magnets were set. The vertical and anterior-upper 60 degrees
      retentive forces of the overdenture were measured one month later. RESULTS: The
      retentive forces of the overdentures after setting magnets were significantly
      greater than that before magnets were set (P < 0.05). There was no significant
      difference in retentive forces between the different parts (P > 0.05). The
      retentive force in vertical direction was greater than that in anterior-upper 60
      degrees direction (P < 0.025). CONCLUSION: Magnetic attachments can significantly
      improve the retention of mandibular complete overdenture. The location of
      magnetic attachments greatly influences the retentive force of the overdenture.

PMID- 14650992
TI  - [Correction of malmaxillomandibular relation with therapeutic complete denture].
AB  - OBJECTIVE: The purpose of this study is to evaluate the effect of therapeutic
      complete denture in rectifying malmaxillomandibular relation of complete.
      METHODS: 11 patients were treated with therapeutic complete denture, of which the
      maxillary premolars and molars were artificial ceramic teeth and mandibular
      premolar and molar region was just like a splint. The changes before and after
      the treatment were recorded by mandibular kinesiograph(MKG). The effect was
      evaluated by self-control comparison. RESULTS: After rectifying, the
      concentration of the closing locus end position evidently increased, the symmetry
      of mandible motion significantly improved, CRO-ICO three-dimensional slide range
      decreased and moreover, the teeth had even and stable contact during sliding.
      CONCLUSION: The temporary therapeutic complete denture had a fair effect in
      rectifying malmaxil-lomandibular relation of edentulous patients.

PMID- 14650993
TI  - [Clinical analysis of the patients with burning mouth syndrome].
AB  - OBJECTIVE: Clinical data of burning mouth syndrome were investigated in detail
      and the relation to pain was analyzed in order to find a clue to clinical
      treatment. METHODS: 78 patients with burning mouth syndrome were examined
      carefully and 7 factors that related to the degree of pain were analyzed with
      multivariate stepwise regression. RESULTS: The study demonstrated that the
      psychological disorder, autonomic nerves system abnormity, oral dryness and high
      extravasated blood level were positively related to the degree of pain.
      CONCLUSION: The study suggested that psychotherapy, improvement of autonomic
      nerves system, treatment for oral dryness and Chinese traditional therapy of
      invigoration of blood circulation were of great importance in curing burning
      mouth syndrome.

PMID- 14650994
TI  - [Clinical application of maxillary endossenous implant with edentulous ridge
      expansion technique].
AB  - OBJECTIVE: To evaluate the application and the effect of edentulous ridge
      expansion(ERE) technique in maxillary endossenous implant placement. METHODS: 49
      patients with maxillary alveolar ridge atrophy received edentulous ridge
      expansion using condenser. In order to be similar to natural root, dental
      implants were selected and placed to tooth missed sites according to the
      requirements of aesthetics, function and dimension. RESULTS: 49 patients with
      atrophied alveolar ridge received 86 implants. The labio-lingual width augmented
      from 3.3 to 5.4 mm and the alveolar ridge height from 2 to 7 mm 6 months after
      operation. The implants osseintergrated tightly with alveolar bone and second
      step prosthesis was performed 6 months after implant placement. CONCLUSION: The
      edentulous ridge expansion technique can meet the requirements of aesthetics and
      function and is applicable to endossenous implant placement in maxilla. The
      method is simple and valuable to clinical application.

PMID- 14650995
TI  - [Correlations among mood disorder, serum interleukin-2 and interleukin-6 in
      patients with burning mouth syndrome].
AB  - OBJECTIVE: To examine serum IL-2 and IL-6 levels in BMS patients with or without
      depression and make clear the relationship between serum IL-2, IL-6 and mood
      disorder. METHODS: Serum IL-2 and IL-6 were examined in 48 BMS patients by means
      of ELISA. The Hamilton Depression Rating Scale (HDRS) was used to evaluate the
      depressive symptomatology. RESULTS: There was no significant difference in serum
      IL-2 and IL-6 among BMS patients with or without depression. Mood disorder was
      not correlated to serum IL-2 and IL-6, but positively correlated to pain levels.
      CONCLUSION: Depression status may not influence serum IL-2 and IL-6 levels
      significantly, but it has a relationship with BMS. The HDRS can be used to
      determine depression status in BMS patients in order to help clinical treatment.

PMID- 14650996
TI  - [Influence to maxillary development by repairing denudated palates with buccal
      mucosa and palatal mucosa].
AB  - OBJECTIVE: To provide experimental data of different oral mucosa suitable to
      repair denudated palate. METHODS: Thirty Japanese white rabbits (5 weeks old)
      were divided into three groups: I group (left hard palate was denudated with
      right side intact), II group and III group (both sides of the hard palate were
      denudated with right side repaired by palatal mucosa or buccal mucosa
      correspondingly). Then the effect of different transplanted mucosa on preventing
      maxillary deformity was investigated and compared. RESULTS: Maxillary development
      in the three groups was same and no significant differences among them were
      discovered. CONCLUSION: Buccal mucosa is effective in serving as reparative
      tissue for preventing maxillary deformity.

PMID- 14650997
TI  - [A study on microstructures and heat reaction zone of laser-melted and cast post
      keepers].
AB  - OBJECTIVE: In order to introduce the laser welding technology into root-cap
      making, this study compared the surface characters and internal structures of
      laser-melted and cast post-keeper to provide experimental data for clinical
      application of the technique. METHODS: Using untreated keeper as the control
      group, the surface characters and metallographic structures of the keepers were
      examined by stereomicroscope, metallographic microscope and SEM, and element
      analysis were conducted with EPMA. RESULTS: The laser-melted post-keeper
      basically kept the original smooth and the internal structure of the keeper, the
      heat reaction zone was extremely small and elements diffused mutually around the
      fusion zone obviously. While in the cast post-keeper, the surface was rough and
      had an oxide-layer. The internal structure changed and a fusion band formed
      between the base alloy and the keeper, but element diffusion was limited to the
      fusion zone. CONCLUSION: Compared with casting, laser welding technique
      demonstrated less influence on the surface and internal structure of the keepers.

PMID- 14650998
TI  - [The measurement of retentive force of laser-melted and cast post-keepers of
      Magfit magnetic attachments].
AB  - OBJECTIVE: In order to compare the influence of casting and laser welding on
      magnetic retentive force, the magnetic retentive forces of laser-melted and cast
      post-keepers of the magnetic attachments were measured in vitro. METHODS: 5 cast
      and 6 laser-melted post-keeper specimens (Magfit MD800) were formed,
      respectively. Using untreated keeper as control group, the vertical magnetic
      retentive forces were measured by a universal testing machine. RESULTS: The
      average vertical magnetic retentive force of the laser-melted post-keeper group
      and the cast post-keeper group in vitro were (4.223 +/- 0.217,0)N, (3.792,9 +/-
      0.296,4)N, respectively. Compared with the cast post-keeper group, the average
      vertical magnetic retentive force of the laser-melted post-keeper groups was much
      higher in vitro (P < 0.05). CONCLUSION: Laser welding had less influence on the
      magnetic retentive force of the magnetic attachments than casting.

PMID- 14650999
TI  - [Evaluation of in vitro cario-static effect of Galla chinensis with biofilm
      model].
AB  - OBJECTIVE: To evaluate the in vitro cario-static effect of Galla chinesis with
      biofilm model. METHODS: A four-organism bacterial consortium was cultured in a
      biofilm model on hydroxyapatite (HA) discs in a continuous culture system and
      exposed to repeated solution pulsing. There were three groups with different
      solution pulsed in the model: negative control group was pulsed with distilled
      water, positive control group was pulsed with 100 mmol/L sucrose solution and
      experimental group was pulsed with 100 mmol/L sucrose solution containing 4.0 g/L
      Galla chinensis. During the experiment, the dynamic changes of pH were recorded.
      After 6 pulses, surface structure of the biofilm was observed with a scanning
      electron microscope and the population on the biofilm was enumerated. RESULTS:
      Galla chinesis significantly inhibited the adherence of Actinomyces naelundii to
      HA disc compared with the control group and facilitated the removal of acid
      products. It was also found that the extra-cellular polysaccharide was reduced
      with the pulsing of Galla chinesis. CONCLUSION: Galla chinesis in the biofilm
      model can partially reduce the cario-genic response of sucrose solution.

PMID- 14651000
TI  - [Detection of the transmitted strains and non-transmitted strains of Mutans
      streptococci by AP-PCR].
AB  - OBJECTIVE: Dental caries is a transmissible infectious disease in which S. mutans
      plays the major role. The purpose of this study was to detect the S. mutans
      transmitted strains and non-transmitted strains by AP-PCR fingerprint for laying
      the foundation of study on the relation between bacterial properties of S. mutans
      and its transmission. METHODS: Plaque samples were obtained from buccal surfaces
      of 20 3-4 years old children and their mothers. Caries experience was scored by
      dmft (DM-FT). Diet regime, breast feeding and care of the children were recorded.
      200 Isolates of S. mutans were detected by S. mutans B medium and confirmed
      biochemically. DNA from each isolate was purified and AP-PCR fingerprinting was
      conducted. Amplicons were separated by electrophoresis in 1.5% agarose gels.
      RESULTS: 45 different patterns among the 200 isolates were found. There were 10
      mothers (50%) and 15(75%) children owning one genotype while 10 mothers and 5
      children owning more than one (2 mothers owning 5 types). The data showed that
      the mothers harbored a more heterogeneous population of S. mutans than their
      children. Comparisons in genotypes between children and their mothers discovered
      that 16(80%) children harbored the same genotypes as their mothers, indicating
      high transmission in the group of people. Detection of the S. mutans transmitted
      strains and non-transmitted strains in mothers demonstrated that 10 (50%) mothers
      harbored not only transmitted strains but also non-transmitted strains,
      suggesting that different strains had different ability of transmission.
      CONCLUSION: AP-PCR was capable of detecting the S. mutans transmitted strains and
      non-transmitted strains. Some S. mutans genotypes had higher ability of
      transmission than others.

PMID- 14651001
TI  - [An experimental study on PAc and GTF gene vaccines of Streptococcus mutans
      against rats caries: antibody levels in saliva and serum].
AB  - OBJECTIVE: The purpose of this study is to examine the levels of salivary SIgA
      and serum IgG induced by pcDNA3-pac and pcDNA3-gtfB immunization, so as to
      testify the antigenity of the two gene vaccines. METHODS: 36 28-day-old Wistar
      rats were divided into 6 groups, among which 3 experimental groups were
      vaccinated with pcDNA3-pac, pcDNA3-gtfB or pcDNA3-pac combined with pcDNA3-gtfB,
      respectively, one positive control was vaccinated with inactive whole cell of S.
      mutans JBP and other two negative controls were injected with the vector pcDNA3
      or PBS buffer, respectively. All vaccines and materials were delivered with 100
      micrograms by submandibular gland injection for 3 times. Then the restricted
      bacterial model of rat was constructed. Following that all rats were fed with
      cariogenic diet Keyes 2000 for 3 months, saliva and serum samples were collected
      to assay SIgA or IgG levels by ELASA. RESULTS: The salivary S-IgA levels both in
      pcDNA3-pac combined with pcDNA3-gtfB group and inactive S. mutans cell group were
      higher than others (P < 0.01). In groups of pcDNA3 and PBS buffer, they were
      lowest (P < 0.01). The serum IgG levels in the three experimental groups and
      positive control were higher than that in negative control (P < 0.05). It was
      important that salivary SIgA in groups of gene vaccine and inactive S. mutans
      vaccination reached its peak at the 11th week after the first inoculation and
      kept until the end of the study. CONCLUSION: Both pcDNA3-pac and pcDNA3-gtfB can
      express immunogenic protein and induce immune responses of mucosal and humoral
      immune system in gnobobiotic rats. It is also indicated that the joint gene
      vaccines immunization is an optimal choice for anticaries strategy.

PMID- 14651002
TI  - [Characteristic changes of acetylcholine receptor in rat lateral pterygoid
      muscles after functional mandibule advancement].
AB  - OBJECTIVE: The purpose of this study was to evaluate the maximum binding(Bmax)
      and affinity(Kd value) changes of acetylcholine receptor (n-AchR) in rat lateral
      pterygoid muscles after functional mandibule advancement. METHODS: 40 five-weeks
      old male Sprague-Dawley rats were equally divided into experimental and control
      group. The mimic functional appliances were used in experiment group and the rats
      were killed after 1, 3, 7, 14 days. Radio-ligand binding assay (RBA) was applied
      to determine the maximum binding(Bmax) and Kd value of n-AchR of lateral
      pterygoid muscle. RESULTS: The Bmax of n-AchR in experimental group was higher
      than that in control group and the Kd value always kept in high level.
      CONCLUSION: The functional orthopedics can increase the Bmax of n-AchR in rapid
      growing rat lateral pterygoid muscles.

PMID- 14651003
TI  - [Study on mechanical compression regulating the proliferation of young growing
      rat masticatory myocyte in vitro].
AB  - OBJECTIVE: To establish an experimental model which was the masticatory myocyte
      culture and force stimulation in vitro and study the proliferation changes of
      cultured masticatory myocytes caused by mechanical compression in young rat.
      METHODS: Flow cytometry (FCM) was used to examine the changes of cellular DNA
      content and cell cycles of cultured masticatory myocytes. RESULTS: The DNA
      content in experimental groups was higher than that in control. After the
      compressive force was applied for 2 hours, the proliferation index (PI) in
      experimental group became higher than that in control. Under a continuous
      pressure for 4 hours, the PI in 2,000 mu strain group reached the maximum (48.9%)
      but the PI in 4,000 mu strain group reached the minimum (39.0%). CONCLUSION: The
      proliferation of masticatory myocytes from young rat increased under certain
      force and certain period of time, but decreased if the force applied was
      overloaded.

PMID- 14651004
TI  - [Effects of investment materials on cast shrinkage of base metal alloys].
AB  - OBJECTIVE: To compare the influence of different investment materials, methods
      and crown height on the cast shrinkage of full crowns made of dental base metal
      alloy. METHODS: All of the 288 wax patterns were made and divided into three
      groups according to their crown height. In every group, wax patterns were
      invested in metal rings and paper rings with three types investment material and
      cast with base metal alloys. Then the inside diameters of castings were measured
      and analyzed by statistical package SPSS. RESULTS: Differences between groups
      invested with the three types of material were significant(P < 0.01). There were
      significant difference between the groups investing with metal rings and paper
      rings(P < 0.01). CONCLUSION: The component of investment material and invested
      ring can affect the cast shrinkage of dental base metal alloy apparently.

PMID- 14651005
TI  - [Both the fetus and the newborn infant can be protected against maternal HIV
      infection. Preventive measures have drastically reduced the number of cases in
      developed countries].

PMID- 14651006
TI  - [Stroke--expansive research with a future. Thrombolytic therapy, rehabilitation,
      medical secondary prevention, injury repair with stem cells...there is a reason
      to optimism].

PMID- 14651007
TI  - [Improved survival after stroke but unchanged risk of incidence].
AB  - Stroke is the third most common cause of death in Sweden. With almost one million
      hospital days pro year, stroke consumes more hospital days than any other somatic
      disease. Each year between 27,000 and 35,000 have a stroke and the mean age of
      stroke patients in Sweden is now 75 years (73 years for men and 77 for women).
      Swedish studies have shown that the stroke incidence has been unchanged or even
      increasing slightly over the lasts decades. However, the stroke mortality has
      decreased, mainly because the case fatality has improved. In patients younger
      than 75 years, the Northern Sweden MONICA study has shown that the case fatality
      has declined from almost 20% 1985 to 11% in 1998. One important reason for the
      declining case fatality is probably the improved care of the stroke patients. In
      1994 half of the patients were treated in a stroke unit. Today 73% of all
      patients are treated in a stroke unit. With an ageing population and an improved
      survival, the prevalence of stroke will increase as long as the incidence is
      unchanged. This means that the number of stroke patients will increase health
      care facilities at all levels. Therefore, it is very important to reduce or
      eliminate risk factors for stroke. Preventing a stroke saves much suffering for
      both patients and relatives and reduces the economic burden for the society.

PMID- 14651008
TI  - [Stroke--risk factors and primary prevention].
AB  - The five major risk factors for stroke are hypertension, smoking, diabetes,
      atrial fibrillation and physical inactivity. All of these are amenable. In
      addition, although hypercholesterolemia is not strongly associated with stroke in
      epidemiological studies, primary prevention with statins provides a modest
      reduction of stroke risk. Unchanged population levels of blood pressure in Sweden
      over the last two decades are accompanied by constant stroke incidence rates. The
      single most cost-effective preventive action is detection and treatment of
      hypertension in the elderly. Antismoking advice and anticoagulants in patients
      with atrial fibrillation and other cardiac sources of embolism also have
      favourable effects relative to costs. There is a dearth of successful population
      based programs to prevent stroke.

PMID- 14651009
TI  - [Antiviral agents reduce HIV transmission from mother to child. Current
      combination therapy results in best suppression of the virus].

PMID- 14651010
TI  - [Adolescents' view on the use of condoms].
AB  - Seven out of ten of the adolescents included in the study had experienced unsafe
      sex with a new partner. Afterwards, 48% worried about STD and 31% worried about
      pregnancy. Teenagers calculate the risk of contracting STD from the looks and the
      reputation of a new partner. Young women and men agree, that both share
      responsibility for the use of condoms, but more often the young women initiate
      the use of condoms. Many participants found it more embarrassing to buy condoms
      than to use them. The participants hoped for improved education in schools and
      less expensive condoms. The adolescents possessed good knowledge concerning how
      to protect themselves, but changes in attitudes are needed. School and youth
      clinics play important roles in this process.

PMID- 14651011
TI  - [What benefits does the patient gain from consulting the general practitioner? A
      review of the literature on the impact of consultations].
AB  - Curing, relieving and comforting are the central tasks of doctors. However, do we
      actually perform these tasks? A literature review was carried out to investigate
      how visits to general practitioners have been evaluated. The review indicates
      that evaluations have focused mostly on whether the patient was satisfied with
      the visit, on changes in the patient's health status, on whether the patient's
      health care consumption has decreased, on whether the patient has complied with
      advice and prescriptions, and to a lesser degree on enablement. These different
      measures have sometimes been related to the working methods of the doctor. In
      these often large, quantitative studies, there is a great deal of uncertainty
      concerning the definition of terms such as "satisfaction" and "health" and also
      concerning the sampling of doctors and patients. The information communicated by
      the studies seldom contributes to increased understanding of the importance of
      consultations to patients.

PMID- 14651012
TI  - [The "Help to Spain" field hospital during the Spanish Civil War. Swedish
      Norwegian contribution for democracy].

PMID- 14651013
TI  - [Carl Peter Thunberg--physician and botanist. "Father" of the thunbergia].

PMID- 14651014
TI  - [Negotiated insurance policies make sick leave profitable for high income
      persons].

PMID- 14651015
TI  - [Panicky measures to reduce sick leave costs].

PMID- 14651016
TI  - [Cooperation when it comes to assessment of occupational injuries is welcomed].

PMID- 14651017
TI  - [European drug policy: welcomed modernization but shortage of political proposals
      concerning industry and research].

PMID- 14651018
TI  - [A fairer comparison between carvedilol and metoprolol is still to be done].

PMID- 14651019
TI  - [Background of iron deficiency as a symptom should be assessed].

PMID- 14651020
TI  - [Health and transfer: which scenario?].

PMID- 14651021
TI  - [Hospital data, cancer registries, and clinical evaluation].

PMID- 14651022
TI  - [The prevention model and the clinical model].

PMID- 14651023
TI  - [Are 10 not enough anymore?].

PMID- 14651024
TI  - [Palestinian genome and scientific publishing].

PMID- 14651025
TI  - [Evaluation of quality of care through hospital discharge reports: an example of
      rectal cancer surgery].
AB  - This study was undertaken to evaluate the usefulness of hospital discharge data
      for monitoring the impact of a regional practice guideline on treatment of
      colorectal cancer. The aims of the study were: i) estimating process and outcome
      indicators; ii) exploring the relationship between patient and hospital
      characteristics and these indicators. Odds ratios (OR) and 95% confidence
      intervals (CI) were adjusted for all risk factors analysed. All 3,614 patients
      undergoing potentially curative resection for rectal cancer in 75 hospitals in
      Piedmont (Italy) between 1997 and 2000 were included. Occurrences of
      abdominoperineal resections (APR), postoperative complications, reinterventions
      and hospital mortality were 16.2%, 11.0%, 5.5% and 4.4%, respectively. APR was
      performed more frequently in patients with distant metastases or urgently
      admitted and by hospitals with a lower volume of cases (< 25 per year) compared
      to hospital with more than 50 cases per year (OR = 1.50, CI = 1.16-1.94). The
      strongest predictors for mortality and complications were: older age, distant
      metastases and urgency of admission. Incidence of complications and of
      reinterventions was also increased among males and in patients with lesions of
      the lower rectum. The rate of complications showed an increasing trend during the
      period, from 8.5% to 14.5% likely reflecting improvement in coding during time.
      Low hospital workload was associated to a reduced risk of complications and
      reinterventions, but there was evidence of underreporting of secondary diagnoses
      and procedures in smaller hospitals. Outcome indicator based on secondary
      diagnoses and procedures are of limited value in monitoring improvement of care
      since they reflect also differences in coding during time and among providers.

PMID- 14651026
TI  - [Nasal sinus cancer registry of the province of Brescia].
AB  - Sinonasal cancers (SNC) are neoplasm uncommon; although strictly related to
      occupational risk factors, in the Brescia province the professional SNC was
      unknown to the Occupational Health Service until short time ago. During the first
      nineties, a retrospective study has carried out to detect SNC and it has showed
      several occupational SNC cases. A local SNC population based Register was
      subsequently set up in 1994, covering 1,044,544 inhabitants. Between 1981 and
      2000 104 SNC, occurred to 74 men and 30 women, have been collected; 98% of them
      was histologically diagnosed and 87.4% was of epithelial type. 36% of cases is
      located on maxillary sinus and the 31.7% on the ethmoidal sinus; 43% is the
      squamous cell carcinoma and 13.7% is the intestinal adenocarcinoma. The annual
      standardised incidence rates (on the Italian population, census 1981, x 100,000)
      on 1990-1995 and 1996-2000 are respectively 1 and 1 in men, 0.3 and 0.4 in women,
      in accordance with those esteemed in others industrialised provinces. In 1990
      1995 the survival observed after 1, 3 and 5 years are respectively 83.8%, 67.7%
      and 48.3%. Anamneses were collected on 83 SNC cases among the epithelial type
      cancer. In men the 33% was exposed to occupational risk factors: wood (13 cases),
      leather (6 cases) and chromium (1 case) dusts. Among works probably related to
      SNC, agriculture, construction and textile reached respectively the 20.5% for
      both sex, 16.4% for men and 18% for women. As for non occupational risk factors
      suggested by literature, smoke appear to be the most relevant, related to the 52%
      of all cases and reaching the 64% in men. Among the women, polyps and inverted
      papillomas (31%), and also chronic rhinitis and sinusitis (13.6%) are more
      frequently observed. Some problems still limiting the work and its usefulness are
      discussed.

PMID- 14651027
TI  - [Reanalysis of mortality in a petrochemical plant producing vinyl chloride and
      polyvinyl chloride].
AB  - OBJECTIVE: To study cancer mortality among main subgroups of workers employed in
      VC/PVC production potentially exposed to toxics and carcinogens. MATERIALS AND
      METHODS: We reanalyzed the mortality of 1,658 males (follow up 1972-1995; 35,626
      person years; 170 deaths) by Poisson regression, adjusting for age, age at
      hiring, calendar period, length of exposure and latency. We calculated the
      relative risks (RR) and the 95% confidence intervals (CI) for PVC baggers (n. =
      197), PVC compound (n. = 403) and autoclave (n. = 209) workers. As an internal
      reference we used two groups of workers: technicians and employees (main
      reference: n. = 202 subjects), with the group of other blue collar workers (n. =
      639) added for statistical purposes only (minor reference: n. = 841 subjects).
      RESULTS: Pooling the four subgroups of exposed workers, the comparison with the
      main reference group allowed us to detect increased mortality from all causes of
      death (RR = 2.09; CI = 1.09-4.00; 160 deaths), all tumours (RR = 1.53; ns; 81
      deaths), lung cancer (RR = 2.05; ns; 29 deaths) and cardiovascular diseases (RR =
      3.57; ns; 29 deaths). The analysis for each specific subgroup revealed increased
      mortality from all causes of death among both PVC baggers (RR = 2.66; CI = 1.27
      5.59) and PVC compound workers (RR = 2.68; CI = 1.36-5.27). Comparison of the
      minor reference group with the overall population of exposed workers showed
      increased RRs for other diseases, namely, liver tumour (RR = 4.08; ns; 9 deaths),
      lymphomas and leukaemia (RR = 2.97; ns; 7 deaths) and liver cirrhosis (RR = 3.30;
      ns; 11 deaths). The analysis for each specific subgroup revealed significantly
      increased RR for all tumours among PVC compound workers (RR = 1.74; CI = 1.06
      2.85), for lung cancer among PVC baggers workers (RR = 3.04; CI = 1.15-7.99) and
      for liver cancer (RR = 9.57; CI = 1.69-54.1) and liver cirrhosis (RR = 6.32; CI =
      1.37-29.07) among autoclave workers. In addition, the two deaths from brain
      tumour were observed among PVC compound workers. CONCLUSIONS: To highlight the
      risk previously reported in the literature and to reduce the possible dilution
      effect (due to comparison bias, healthy worker effect), it proved
      methodologically pivotal to separate exposed and probably unexposed workers
      (considered as an internal reference group).

PMID- 14651028
TI  - [Asthma and allergies in childhood in Rome: Italian contribution to the ISAAC
      II].
AB  - A study about the frequency of respiratory and allergic disorders in childhood
      was carried out in Rome, during the 2000-2001 school year. This survey represents
      the Italian contribution to the second phase of the International Study on Asthma
      and Allergies in Childhood (ISAAC Phase Two). A properly filled in ISAAC Phase II
      questionnaire was returned by parents of 1,760 children attending the fifth grade
      in primary school (83.5% of the target). Prick tests were performed to provide an
      objective measure of atopy, defined as skin reactivity to one or more allergens.
      The presence of visible flexural dermatitis was determined through skin
      examination. Lifetime prevalence for asthma, allergic rhinitis and eczema was
      12.4%, 13.2% and 15.1%, respectively. Period prevalence in the last 12 months was
      7.0% for attacks of wheezing or whistling in the chest, 9.1% for rhinitis
      symptoms, and 9.5% for dermatitis symptoms. A total of 1.6% of the children under
      examination had a visible flexural dermatitis. Of the children who performed
      prick test, 31.8% was skin positive at least to one of the adopted allergens. An
      international comparison with the results of other ISAAC Phase Two studies
      (conducted in Albania, Germany, Hong Kong, UK and Sweden) has shown that Rome and
      Hong Kong were the areas with the highest prevalence rate for atopy, but had
      comparatively low proportions of asthmatic subjects. This inconsistency suggests
      that factors other than atopy could be responsible for the geographic
      epidemiological distribution of asthma.

PMID- 14651029
TI  - [Epidemiologic study Salus domestica: evaluation of health damage in a sample of
      women living near the Malpensa 2000 airport].
AB  - The opening of the new Malpensa 2000 Airport worried people living in the
      neighbouring towns about possible effects of acoustic and air pollution on health
      status. For this reason, Varese Health Unit set up a study involving housewives
      and General Practitioners. This study has been carried out in 3 Areas: A Area,
      bordering the airport, B Area, at intermediate distance, and C Area, at long
      distance. On the whole, 932 housewives (18 to 64 years old) and 92 General
      Practitioners, were involved. The questionnaire, distributed to housewives
      between May 1st and November 30th 2000, was filled out in the doctor's surgery
      who furthermore added clinical data. Chi-square statistics were calculated to
      test the association between living area and personal data, behavioural and
      environmental characteristics, and reported disorders. To describe possible
      interrelationships between living Area and the answers supplied by housewives and
      General Practitioners the multiple correspondence multivariate analysis technique
      was applied. The housewives living next to the airport (A area) frequently report
      insomnia, nocturnal waking, anxiety and difficulty in hearing words. The
      multivariate analysis has shown a relationship between recently increasing noise
      noted by the housewives, and the area where they live, as well as a noticeable
      coherence between the answers given by the housewives and those given by the
      General Practitioners, who reported higher frequencies of cephalgy, allergies,
      anxiety neurosis, medical consultation, benzodiazepine's and sleeping disorder's
      prescriptions in A Area compared to C Area. The airport's presence seems to be
      associated with the onset of subjective disorders in neighbouring population.
      Some of these disorders, in particular neuropsychological ones, are clinically
      confirmed by General Practitioners, and are consistent with different noise
      exposure levels.

PMID- 14651030
TI  - [Air pollution: how many victims?].
AB  - Air pollution is associated with short- and long-term effects on "natural"
      mortality. Both can be viewed as the worsening of population health, more
      pronounced for long-term effects. A method for estimating this burden is
      proposed.

PMID- 14651031
TI  - [The concept of health in Italian occupational health legislation].
AB  - This study describes the evolution of the concept of health in Italian
      occupational health legislation (1900-2001). Mental health dimensions at work
      (such as reduction in monotony and repetitiveness, mental risks in pregnancy and
      so on) were introduced only recently. This can be explained with: 1) poor working
      conditions; 2) the delay of the occupational health community in including mental
      health in the concept of health; 3) the gap between scientific knowledge of risk
      factors for mental health and legislation aimed at prevention.

PMID- 14651032
TI  - [The smoke free movies initiative in the United States].
AB  - Movies influence fashion, lifestyles, and represent smoking as an acceptable
      behaviour. In fact the greatest tobacco companies built relationships with
      Hollywood's actors and producers, in order to show smoking and cigarette brands
      in films. All over the world laws have been developed, in order to restrict
      smoking and tobacco advertising. Films showing tobacco do not violate these laws,
      even in those states where tobacco advertising is restricted. Moreover, films are
      better than any other commercial advertisements because the audience is total
      unconscious of the sponsor's involvement. Stanton Glantz, Medicine Professor at
      San Francisco University, is the voice of the movement for smoke-free movies. A
      lot of studies show that cigarette smoking is more frequently in '90s movies than
      in 60's and 70's movies. The smoking actors seem to be attractive, strong,
      healthy and successful. Films showing smoking influence tomorrow's customers:
      adolescents. Teenagers watching "smoking films" are the most exposed to start
      smoking. Hence the need to educate Hollywood industry, in order to have smoke
      free movies.

PMID- 14651033
TI  - Mental retardation and the death penalty: a guide to State Legislative issues.

PMID- 14651034
TI  - Weekly malaria surveillance in Zimbabwe.

PMID- 14651035
TI  - Center specificity in the limited sampling model (LSM): can the LSM developed
      from healthy subjects be extended to disease states?
AB  - BACKGROUND AND OBJECTIVES: Area under the curve (AUC) can be related to the
      therapeutic or toxic effect of a drug. In order to accurately measure AUC,
      multiple blood samples are required, but in a clinical setting, frequent blood
      sampling from the patients is time-consuming and expensive. The limited sampling
      model (LSM) is one of the approaches that is gaining popularity due to its
      simplicity for the estimation of AUC using 1 - 3 samples. Despite its simplicity,
      the LSM has some shortcomings. One of the major drawbacks of the LSM is that the
      LSM developed under a given condition may not be extended to other conditions.
      For example, the LSM developed from healthy subjects may not be extended to
      disease states such as renal or hepatic impairment or vice versa. This
      characteristic of the LSM can be referred to as "center-specific". In this
      investigation, the LSM developed from the healthy subjects was used to predict
      AUC in patients with renal or hepatic impairment. METHODS: Two sets of simulated
      plasma concentration versus time data for 2 antihypertensive drugs and measured
      plasma concentration versus time data for 2 representative drugs (A and B) were
      used in the analysis. RESULTS AND CONCLUSION: The results of the study indicate
      that the LSM developed from healthy subjects is inadequate to predict AUC in
      patients with hepatic or renal impairment, indicating center specificity of the
      LSM.

PMID- 14651036
TI  - Doctors who performed abortions before Roe v. Wade.

PMID- 14651037
TI  - [Organotypic cultures of free-floating sections of human embryonic medulla
      oblongata].
AB  - The aim of the present study was the development of organotypic culture of
      embryonic nerve tissue of human brain, which is necessary for the study of the
      effect of blood serum factors in mental diseases and their medicinal treatment.
      For the cultivation the sections of medulla oblongata were taken from human 9-10
      week embryos obtained at legal medical abortion. Free-floating sections were
      cultured using a modified roller method for 4 weeks. By using the methods of
      light and electron microscopy, as well as of immunocytochemistry, it was
      demonstrated that within the cultured sections the differentiation and growth of
      neurons, astrocytes and microgliocytes took place accompanied by the formation of
      synaptic contacts and the establishment of glial-neuronal relationships,
      characteristic to the organotypical cultures. However, along with the
      differentiated neurons and glial cells, undifferentiated cellular elements were
      partially retained, that had the signs of neuronal and glial stem cells and
      progenitor cells. The studies performed have demonstrated that the method of
      organotypic roller culture of free-floating sections of human embryonic brain
      tissue could be applied for the study of the processes of neuronal and gliocyte
      development, mechanisms of neurotoxicity and neuroprotection using various
      morphological (including stereological) and biochemical research methods.

PMID- 14651038
TI  - Micromachining microcarrier-based biomolecular encoding for miniaturized and
      multiplexed immunoassay.
AB  - Micromachining techniques, which originated in the microelectronics industry,
      have been employed to manufacture microparticles bearing an engraved dot-type
      signature for biomolecular encoding. These metallic microstructures are
      photolithographically defined and manufactured in a highly reproducible manner.
      In addition, the code introduced on the particle face is a straightforward
      visible feature that is easily recognizable with the use of optical microscopy.
      The number of distinct codes theoretically could be many thousands, depending on
      the coding element numbers. Such microparticles are, thus, with appropriate
      surface organic functionalizations, ideal for encoding biomolecular libraries and
      serving as a platform for developing high-throughput multiplexed bioassay schemes
      based on suspension array technology. As proof of this statement, we demonstrated
      that encoded microparticles tagged with antibodies to human immunoglobulin
      classes are capable, using imaging detection as the interrogating approach, of
      high sensitivity and high specificity, as well as multiplexed detection of the
      respective antigens in a microliter-sample volume.

PMID- 14651040
TI  - Cassandra.

PMID- 14651039
TI  - The Lupus Foundation as an additional source for case ascertainment: developing a
      community-based lupus registry.
AB  - OBJECTIVE: To determine whether the local Lupus Foundation of America (LFA)
      chapter would provide a unique source of additional lupus incident cases for a
      population-based incidence registry of SLE. METHODS: We reviewed membership and
      telephone records from the LFA to identify potential lupus cases. These potential
      cases were compared with the names on our previously developed incidence
      registry. Non-matches were interviewed concerning demographic characteristics and
      the signs and symptoms of lupus. RESULTS: Of the 449 potential lupus cases
      identified through the LFA Western Pennsylvania Chapter (WPC), 108 (24%) were
      already in the incident lupus registry. Of the remaining unmatched cases, 26
      reported a diagnosis of lupus in Allegheny County between 1985 and 1990. Of
      these, 5 patients met the criteria for definite or probable lupus. CONCLUSION:
      The LFA-WPC provided a negligible advantage in identifying additional incident
      lupus cases to those already identified through an established registry.

PMID- 14651042
TI  - [AIDS: success of a change of mind].

PMID- 14651043
TI  - Cumulative subject index, volumes 40-72.

PMID- 14651041
TI  - [Regarding public health there is no doubt that in Germany and Europe that it is
      driven by economic considerations].

PMID- 14651044
TI  - Abstracts of the Middle East Cardiostim Congress. 2-4 October 2003, Beirut,
      Lebanon.

PMID- 14651045
TI  - USP Veterinary Pharmaceutical Information Monographs--Antibiotics.

PMID- 14651047
TI  - Abstracts of the 51st Annual Meeting of the Irish Gerontological Society. 26-27
      September 2003.

PMID- 14651046
TI  - Abstracts of the IX Congress of SOLACI (Latin American Society of Interventional
      Cardiology) and XXV Congress of SBHCI (Brazilian Society of Hemodynamics and
      Interventional Cardiology. 23-25 July 2003, Sao Paulo, Brazil.

PMID- 14651048
TI  - NASA's global reach.

PMID- 14651049
TI  - Lawmakers battle for reform on many fronts.
AB  - In Washington, much of the attention of the nation's leaders is focused on the
      economy, on next year's election, and on the war's aftermath in Iraq. Polls show
      that a restive nation wants more jobs and fewer casualties in the war on terror.
      In the world of aerospace, few topics seem to be headline-grabbers lately, but
      the lawmakers are always working on air and space issues--some of them very
      familiar to Americans. The U.S. program for manned spaceflight remains
      controversial and a firm date for a return to flight elusive. The little-known
      air war in Colombia is receiving more attention than many in Washington would
      like. And the Air Force plan to lease air-refueling tankers continues to draw
      flak from the Hill.

PMID- 14651050
TI  - Medical devices: classification of the dental sonography device and jaw tracking
      device. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the dental sonography
      device into class I, when it is used to monitor temporomandibular joint sounds,
      and into class II, when it is used to interpret temporomandibular joint sounds
      for the diagnosis of temporomandibular joint disorders and associated orofacial
      pain. FDA is classifying the jaw tracking device into class I, when it is used to
      monitor mandibular jaw positions relative to the maxilla, and into class II, when
      it is used to interpret mandibular jaw positions relative to the maxilla, for the
      diagnosis of temporomandibular joint disorders and associated orofacial pain.
      Elsewhere in this issue of the Federal Register, FDA is announcing the
      availability of a guidance document that will serve as the special control for
      this device. FDA is taking this action under the Federal Food, Drug, and Cosmetic
      Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976
      amendments), the Safe Medical Devices Act of 1990 (the SMDA), the Food and Drug
      Administration Modernization Act of 1997 (FDAMA) and the Medical Device User Fee
      and Modernization Act of 2002 (MDUFMA).

PMID- 14651051
TI  - Conversations with Norman Augustine. Interview by Linda Voss.

PMID- 14651052
TI  - Cumulative author, subject, compound and special issue indexes volumes 952-1000
      (2002-2003).

PMID- 14651053
TI  - Cumulative index volumes 1-45.

PMID- 14651054
TI  - Abstracts of the 30th Annual Meeting of the Japanese Society of Toxicology. 18-20
      July 2003, Sagamihara City, Japan.

PMID- 14651055
TI  - Abstracts of the 7th Annual Meeting of the Heart Failure Society of America, 21
      24 September 2003.

PMID- 14651056
TI  - Can CO2 help harvest minerals on Mars?
AB  - When astronauts first go to Mars, it will be difficult for them to bring
      everything they need to survive. Even the first tentative explorations could last
      as long as two years. However, spaceships can carry only limited supplies. "We
      might have to do what explorers have done for ages: live off the land," says
      chemical engineer Ken Debelak of Vanderbilt University. It is a meager
      atmosphere, compared to Earth's, and it is about 95% carbon dioxide. This,
      however, turns out to be an advantage. The CO2, says Debelak, can be used to
      harvest almost everything else.

PMID- 14651057
TI  - Society for Free Radical Biology and Medicine 10th Annual Meeting. November 20
      24, 2003. Seattle, Washington, USA. Abstracts.

PMID- 14651058
TI  - Columbia: what went wrong?
AB  - The results of the Gehman board's exhaustive investigation of the Columbia
      accident (STS-107) will have far-reaching effects on the U.S. space program.

PMID- 14651059
TI  - Roy Zuckerberg: sharing the lessons of corporate culture. Interview by Laurie
      Larson.

PMID- 14651061
TI  - Abstracts of the German Society of Electron Microscopy 31st Annual Meeting.
      Dresden, Germany, 7-12 September 2003.

PMID- 14651060
TI  - [Abstracts of the 20th Annual Meeting of the Brazilian Society of Dental
      Research. 30 August-3 September 2003, Sao Paulo, Brazil].

PMID- 14651062
TI  - New cell-based technologies in bone and cartilage tissue engineering. II.
      Cartilage regeneration.
AB  - A tissue engineering, cell-based therapeutic approach could be essential for
      extensive bone or cartilage reconstruction. This article is divided in two
      chapters and describes new cell-based surgical techniques for cartilage and bone
      reconstruction. The second part of the article, regarding cartilage repair,
      describes a new arthroscopic surgical technique for tissue engineered cartilage
      grafting. A 3-dimensional hyaluronic acid support is used for autologous
      chondrocyte culturing. The technique reduces morbidity of classic autologous
      implant avoiding open surgery and periosteal flap use. With this technique is
      possible to reduce the patient morbidity, time and cost of surgery.

PMID- 14651063
TI  - Editor's retraction.

PMID- 14651064
TI  - 75th anniversary series. The 1990s: visions of the future.

PMID- 14651065
TI  - Working smart. Does the privacy rule allow us to release patient information over
      the telephone without authorization?

PMID- 14651067
TI  - Orthopaedic proceedings: 2001, 2002, 2003.

PMID- 14651069
TI  - Special issue: Biological threats.

PMID- 14651070
TI  - Abstracts of the Canadian Council of Cardiovascular Nurses (CCCN) Annual Meeting.
      Toronto, Ontario, Canada, October 2003.

PMID- 14651071
TI  - Following interests yields dynamic career. Interview by Jessica Squazzo.

PMID- 14651072
TI  - Abstracts of the 10th Annual Conference of the International Society for Quality
      of Life Research. November 12-15, 2003. Prague, Czech Republic.

PMID- 14651073
TI  - Abstracts of the 26th Annual San Antonio Breast Cancer Symposium. December 3-6,
      2003.

PMID- 14651074
TI  - Abstracts of the 5th National Congress of Medical Oncology. 21-24 October 2003,
      Rome, Italy.

PMID- 14651075
TI  - JCAHO's new accreditation process.

PMID- 14651076
TI  - Translation, difference and ontological fluidity: cerebral angiography and
      neurosurgical practice (1926-45).
AB  - Cerebral angiography is nowadays a standard test in neurosurgical treatment. The
      coupling between such a diagnostic technique and neurosurgical practices is the
      outcome of a complex story. This paper explores that complexity. It does so by
      exploring the continuities and discontinuities between the multiple definitions
      and uses of angiography in the first 20 years of its history. It also
      investigates the relations between process and narrative in S&TS research, and
      suggests that it is possible to turn dis/continuity into an empirical question,
      viewing it as internal to the processes of socio-technical innovation as it
      becomes available in the practical engagements of the actors involved in those
      processes.

PMID- 14651077
TI  - Proceedings of the 3rd International Conference on Innovations and Challenges in
      Prostate Cancer: Prevention, Detection and Treatment. November 15-16, 2002,
      Cambridge, Massachusetts, USA.

PMID- 14651078
TI  - Isolated deep cerebral venous thrombosis diagnosed on CT and MR imaging. A case
      study and literature review.
AB  - Cerebral venous thrombosis represents less than 5% of all strokes. Isolated
      cerebral deep venous thrombosis is very rare. We present a case of isolated
      thrombosis of the internal cerebral veins and the vein of Galen diagnosed on CT
      and MRI, and we review the literature. We emphasize the pathognomonic signs on CT
      and MRI necessary for an early diagnosis obviating conventional angiography.
      Early diagnosis and treatment may avoid potentially devastating consequences.

PMID- 14651079
TI  - Non perforated septum supra-patellaris mimicking a soft tissue tumour.
AB  - Plicae synoviales of the knee are well known to present as anterior knee pain but
      can also cause blocking, clicking, and swelling of the knee mimicking pathology
      such as meniscal tears or other internal derangements, and even mono-arthritis.
      Embryologically, the knee is divided into a medial and lateral compartment and a
      supra-patellar pouch by thin membranes of synovium. Incomplete involution of
      these membranes gives rise to a plica. When there is no involution at all, the
      membrane is called a septum. There are three frequent types of plicae/septa: a
      suprapatellar, a medial-patellar, and an infra-patellar type. We discuss on a
      patient with a non perforated septum supra-patellaris which resulted in a
      swelling above the knee, mistaken for a soft tissue tumour.

PMID- 14651080
TI  - MR imaging findings of bone marrow changes in patients with cystic fibrosis.
AB  - The purpose of this work was to evaluate bone marrow abnormalities in the lower
      limbs of patients with cystic fibrosis by means of MR imaging. Eight patients
      with cystic fibrosis ranging in age from 16 to 35 years (average age 25.1 years)
      were evaluated with MR imaging of the lower extremities. T1 weighted spin echo
      sequences were obtained in all patients. Pelvis, femora and tibia were imaged in
      the coronal plane whereas the feet were imaged in the sagittal plane. The studies
      were independently evaluated by two musculoskeletal radiologists. The images were
      not mixed with disease-free images, but the readers were completely unaware of
      clinical data. Distribution of haematopoietic and fatty marrow was graded on a 5
      point scale. In five patients, both observers considered marrow distribution as
      probably or definitely abnormal relative to their age. Although our findings are
      very preliminary, our investigation suggests that cystic fibrosis may be added to
      the list of disorders in which bone marrow abnormalities may be observed.

PMID- 14651081
TI  - Cystic insulinoma of the pancreas in a patient with myotonic dystrophy:
      correlation of imaging and pathologic findings.
AB  - We present a case of cystic islet cell tumor of the pancreas in a 60-year old
      male with myotonic dystrophy. A cystic lesion was found with a thick peripheral
      rim, a few intralesional septae and a fluid-debris level on CT and MRI. Image
      characteristics are compared with the pathological findings. MRI demonstrated the
      internal architecture of the lesion more clearly.

PMID- 14651082
TI  - Claudication type lower limb pain in an athlete without atherosclerotic risk
      factors: a case of cystic adventitial disease of the popliteal artery.
AB  - Cystic adventitial disease (CAD) of popliteal artery is a rare cause of lower
      limb claudication. Since its first description in 1947 only about 323 cases have
      been reported in the literature. We report the case of a 45 year old man with CAD
      of the popliteal artery causing progressive left lower leg claudication detected
      by US and Doppler US and characterized with spiral CT angiography. No
      communication with the knee joint could be demonstrated.

PMID- 14651083
TI  - The meniscal ossicle revisited.
AB  - The meniscal ossicle is an infrequent radiographic finding in humans. It often is
      mistaken for an intra-articular loose body. MR imaging is the ideal modality to
      differentiate between these entities. We report the imaging findings of a
      meniscal ossicle in a patient with emphasis on the MR imaging appearance. A
      review of the literature on meniscal ossicles is also presented.

PMID- 14651084
TI  - Pictorial essay. Myositis ossificans circumscripta.
AB  - Myositis ossificans circumscripta (MOC) is a localized, non-neoplastic,
      heterotopic ossification within the muscle. Despite advances in medical imaging,
      it remains difficult to distinguish it from other disorders. As a consequence, a
      biopsy is frequently performed. We illustrate some common findings and non
      specific imaging features of MOC with respect to radiography, computed
      tomography, bone scintigraphy, ultrasonography, and magnetic resonance imaging.
      The differentiation among MOC and its mimics is also presented in order to help
      the radiologists to make an appropriate diagnostic decision.

PMID- 14651085
TI  - Proceedings of the State-of-the-Art Symposium on Diagnostic and Interventional
      Radiology of the Spine, Antwerp, September 7, 2002 (Part two). Upright, weight
      bearing, dynamic-kinetic MRI of the spine: pMRI/kMRI.
AB  - PURPOSE: To review the general clinical utility of the first dedicated magnetic
      resonance imaging (MRI) unit enabling upright, weight-bearing positional
      evaluation of the spinal column (pMRI) during various dynamic-kinetic maneuvers
      (kMRI) in patients with degenerative conditions of the spine. MATERIALS &
      METHODS: This study consisted of a prospective non-statistical analysis of
      cervical or lumbar imaging examinations. All studies were performed on a recently
      introduced whole body MRI system (Stand-Up MRI, Fonar Corp, Melville, NY). The
      system operates at 0.6T using an electromagnet with a horizontal field,
      transverse to the longitudinal axis of the patient's body. Depending upon spinal
      level, all examinations were acquired with either a cervical or lumbar solenoidal
      radiofrequency receiver coil. This unit was configured with a top-front open
      design, incorporating a patient-scanning table with tilt, translation and
      elevation functions. The unique motorized patient handling system developed for
      the scanner allowed for vertical (upright, weight bearing) and horizontal
      (recumbent) positioning of all patients. The top-open construction also allowed
      dynamic-kinetic flexion and extension maneuvers of the spine. Patterns of bony
      and soft tissue change occurring among recumbent (rMRI) and upright neutral
      positions (pMRI), and dynamic-kinetic acquisitions (kMRI) were sought. RESULTS:
      Depending on the specific underlying pathologic degenerative condition,
      significant alterations observed on pMRI and kMRI that were either more or less
      pronounced than on rMRI included: fluctuating anterior and posterior disc
      herniations, hypermobile spinal instability, central spinal canal and spinal
      neural foramen stenosis and general sagittal spinal contour changes. No patient
      suffered from feelings of claustrophobia that resulted in termination of the
      examination. CONCLUSION: To conclude, the potential relative beneficial aspects
      of upright, weight-bearing (pMRI), dynamic-kinetic (kMRI) spinal imaging on this
      system over that of recumbent MRI (rMRI) include: the revelation of occult
      disease dependent on true axial loading, the unmasking of kinetic-dependent
      disease, and the ability to scan the patient in the position of clinically
      relevant signs and symptoms. This imaging unit also demonstrated low
      claustrophobic potential and yielded relatively high-resolution images with
      little motion/chemical shift artifact.

PMID- 14651086
TI  - Functional MRI of the spinal cord: will it solve the puzzle of pain?
AB  - PURPOSE: Whether stimulation of the median nerve could evoke an fMR imaging
      response at 1.5 T in the cervical spinal cord was investigated and the response
      pattern was compared with that obtained by fist clenching. METHODS: Eleven
      subjects performed the fist-clenching task and in seven of them electrical
      stimulation was also applied. fMRI was performed using a T2* sensitive echo
      planar imaging sequence gated by the heartbeat signal. A dynamic cardiac-gated
      T2*-weighted imaging sequence was used to quantify cervical spinal cord
      activation. Cord activation was measured in the sagittal and transverse imaging
      planes. RESULTS: With the fist-clenching task, activation of the spinal cord in
      the cervical intumescence could be seen in seven of eleven subjects in the
      sagittal plane and in six of nine subjects in whom axial images were acquired.
      When median nerve stimulation was applied, cord activation was seen in the
      sagittal images in five out of seven, and in the axial plane in two out of six
      subjects. A consistent cross-sectional localization of the activity measured in
      the spinal cord was not detected, either in terms of the right and left sides or
      in terms of the posterior and anterior directions. CONCLUSION: In the sagittal
      plane, median nerve stimulation at the elbow can evoke an fMR imaging response in
      the lower cervical spinal cord. The activation pattern was comparable with that
      obtained by fist clenching.

PMID- 14651087
TI  - CT-guided percutaneous needle biopsy in spine lesions.
AB  - Vertebral bone biopsy is an accurate, rapid, and cost-effective method to
      diagnose benign and malignant spine lesions. The major complications are
      uncommon. Nondiagnostic or insufficient specimens are encountered in less than
      ten per cent. The accuracy of the biopsy depends on the location and type of the
      lesion, needle system, and biopsy route. The major indications are focal lesions
      with non-specific medical imaging findings, to exclude metastasis in patients
      with known primary malignancy, lesion without response to treatment, no clinical
      improvement in children with diskitis after six weeks of therapy to exclude
      occult tumor and extreme pain due to vertebral collapse. If histology yields only
      peripheral blood elements in an obviously destructive mass, biopsy can be
      repeated, by directing at a slightly different area of the lesion. No more than
      three percutaneous biopsies of the same lesion should be performed.

PMID- 14651088
TI  - Intradiscal electrothermal therapy (IDET).
AB  - The indications of discography include situations in which there is inconsistency
      between the imaging and physical findings. Discography may also be performed
      prior to planned disc therapy such as percutaneous diskectomy or IDET. The
      diagnostic goal of the diskcogram is to reproduce the patient's original pain
      pattern by injection of the disc. If it is determined that the origin of the
      patient's back pain is diskcogenic, disc therapy can be provided by either
      surgical or non-surgical means. The non-surgical disc therapy includes steroid
      injections, IDET, or even percutaneous diskectomy.

PMID- 14651089
TI  - Percutaneous vertebroplasty.
AB  - Percutaneous vertebroplasty (PV) is a safe and effective treatment for relieving
      pain in patients complaining of severe back pain induced by osteoporotic or
      neoplastic compression fractures. The success rate exceeds 90% and the
      complication rate is lower than 1%. Most of the complications are transient. The
      classic indication for PV is severe, persistent, and incapacitating focal back
      pain not responding to standard medical therapy and related to one or more
      collapsed vertebral bodies of 4 to 12 weeks duration.

PMID- 14651090
TI  - Proceeding of the meeting of The KBVR-SRBR Osteo-Articular section, Brussels,
      June 21, 2003. Cystic lesions around the knee.

PMID- 14651091
TI  - Images in clinical radiology. Calcinosis cutis following calcium gluconate
      extravasation.

PMID- 14651092
TI  - Images in clinical radiology. Double bubble sign in the newborn.

PMID- 14651093
TI  - Crystal engineering, where from? Where to?

PMID- 14651094
TI  - Rational design of porous titanophosphates.
AB  - To rationally design new nanoporous materials based on titanophosphates, a small
      library of titanium phosphate crystalline nanoporous compounds has been build up
      and its compounds have been investigated by X-ray diffraction and by in- and ex
      situ NMR. The main trends of the unusual titanium solution chemistry, of the
      prenucleation building units and of their assembling have been established. The
      classical trial and error strategy can therefore be replaced by a better control
      of the steps leading to the final targeted network.

PMID- 14651095
TI  - Improved transparency--nonlinearity trade-off with boroxine-based octupolar
      molecules.
AB  - A series of octupolar molecules derived from the boroxine framework were designed
      and their optical nonlinearities were investigated by performing harmonic light
      scattering experiments in solution; the molecules were found to combine excellent
      transparency in the near UV-visible region (lambdamax < or = 280 nm) and
      significant first-order hyperpolarisabilities (up to beta(0) = 56 x 10(-30) esu).

PMID- 14651096
TI  - A novel water-soluble and self-doped conducting polyaniline graft copolymer.
AB  - A water-soluble and self-doped conducting polyaniline graft copolymer,
      poly(styrenesulfonic acid-g-aniline) (PSSA-g-PANI), was first synthesized and its
      electrical properties were investigated.

PMID- 14651097
TI  - Correlation of chemical reactivity of Nudaurelia capensis omega virus with a pH
      induced conformational change.
AB  - Nudaurelia capensis omega virus, which undergoes one of the largest known
      structural changes of icosahedral viruses in response to its environment,
      exhibits chemical reactivity which depends on its conformational state.

PMID- 14651098
TI  - Two-dimensional metamagnet composed of cyano-bridged CuII-WV bimetallic assembly.
AB  - Two-dimensional cyanide-bridged copper(II) octacyanotungstates(V), [(Cu(3
      CNpy)2(H2O))2(Cu(3-CNpy)2(H2O)2)(W(CN)8)2] (3-CNpy = 3-cyanopyridine) (1) and
      [(Cu(4-CNpy)2)2(Cu(4-CNpy)2(H2O)2)(W(CN)8)2] x 6H2O (4-CNpy = 4-cyanopyridine)
      (2), were prepared and these compounds exhibited metamagnetic behavior with Neel
      temperatures of 8.0 K (1) and 4.4 K (2).

PMID- 14651099
TI  - Small molecule fixation by a dithiadiazolyl radical: X-ray crystal structures of
      (CF3C6H3FCNSSN)2 and (CF3C6H3FCNSSN)2 x G (G = N2, Ar, CO2 and SO2).
AB  - The title dithiadiazolyl radical, F3CC6H3FCNSSN (1) forms inclusion structures
      with small molecules (such as N2, CO2, Ar and SO2) when sublimed under partial
      atmospheres of the guest.

PMID- 14651100
TI  - Formation of nickel-thiolate aggregates via reaction with CH2Cl2.
AB  - Reaction of the mononuclear nickel-thiolate complex [Ni(L1)(dppe)] with CH2Cl2
      affords the novel pentanuclear complex [Ni5Cl2(L1)4(dppe)2], while [Ni(L1)(dcpe)]
      reacts with CH2Cl2 to give the binuclear species [Ni2Cl2(L2)(dcpe)2] in which two
      L1 units are linked by a methylene group derived from CH2Cl2.

PMID- 14651101
TI  - A rational synthetic route leading to 3d-3d'-4f heterospin systems: self-assembly
      processes involving heterobinuclear 3d-4f complexes and hexacyanometallates.
AB  - A novel heterospin system, [(CuL)Gd(H2O)3(Fe(CN)6)] x 4H2O, is obtained by
      reacting the mononuclear complex, [CuL], with gadolinium(III) nitrate, followed
      by the substitution of the nitrato groups with [Fe(CN)6](3-) ions (L2- = N,N'
      propylenedi(3-methoxysalicylideneiminato)).

PMID- 14651103
TI  - Morphosynthesis of complex inorganic forms using pollen grain templates.
AB  - Porous micron-sized particles of silica, calcium carbonate or calcium phosphate
      are prepared with complex morphologies by template-directed synthesis employing
      intact pollen grains; the materials adsorb and release drug molecules and can be
      functionalized with metallic or magnetic nanoparticles.

PMID- 14651102
TI  - Evidence from engineered gene fusions for the repeated use of a module in a
      modular polyketide synthase.
AB  - Functional evidence for programmed loss of co-linearity on the borrelidin modular
      polyketide synthase (PKS) is presented.

PMID- 14651104
TI  - Total synthesis of (+/-)-acetoxyodontoschismenol using zirconium chemistry.
AB  - The dolabellane diterpene (+/-)-acetoxyodontoschismenol has been synthesised for
      the first time by a short route in which a three component coupling on zirconium
      is used to assemble all the carbons needed for the skeleton in onepot.

PMID- 14651105
TI  - Synthetic studies towards congeners of phomactin A. Re-examination of the
      structure of Sch 49028.
AB  - The total syntheses of the epoxy cyclic hemiacetal structures 8 and 9, which are
      isomeric with the structure 6 proposed for the phomactin known as Sch 49028
      isolated from the marine fungus Phoma sp. are described. Neither of these
      structures showed spectroscopic data consistent with those reported for the
      purported natural product, adding credibility to the proposal that the structure
      Sch 49028 does not exist in nature and that its NMR spectroscopic data should
      have been assigned as phomactin A (1).

PMID- 14651106
TI  - Using two photon microscopy to quantify enzymatic reaction rates on polymer
      beads.
AB  - Two-photon fluorescence microscopy was introduced as a tool to assess enzyme
      accessibility and to quantify enzyme reactions rates on solid supports.

PMID- 14651107
TI  - Multiple hydrogen bonding-based fluorescent imprinted polymers for cyclobarbital
      prepared with 2,6-bis(acrylamido)pyridine.
AB  - A cyclobarbital-imprinted polymer was prepared using a fluorescent functional
      monomer, 2,6-bis(acrylamido)pyridine, and the polymer showed not only selective
      binding of cyclobarbital but also enhancement of fluorescence intensity,
      suggesting that the polymer could be utilized as a selective fluorescence probe.

PMID- 14651108
TI  - Different thermal reactivity of a 1,2-thiaphospholo[a]phosphirane in free and
      metal carbonyl complexed form.
AB  - The W(CO)5 and Fe(CO)4 complexes of the bicyclic phosphirane 3,5,6,6-tetraphenyl
      1-phospha-2-thiabicyclo[3.1.0]hex-3-ene undergo a thermal 2-phenylphosphirane -->
      dihydrophosphaisoindole ring expansion, while the free phosphirane suffers both a
      [2 + 1] cycloreversion and a fragmentation yielding a butadienyl sulfide.

PMID- 14651109
TI  - Phase transitions in calcium nitrate thin films.
AB  - Calcium carbonate is a ubiquitous mineral and its reactivity with indoor and
      outdoor air pollutants will contribute to the deterioration of these materials
      through the formation of salts that deliquesce at low relative humidity (RH). As
      shown here for calcium nitrate thin films, deliquescence occurs at even lower
      relative humidity than expected from bulk thermodynamics and lower than the
      recommended humidity for the preservation of artifacts and antiques.

PMID- 14651110
TI  - First in-situ SAXS studies of the mesostructuration of spherical silica and
      titania particles during spray-drying process.
AB  - Meso-organisation of SiO2 and TiO2 particles prepared by spray drying have been
      for the first time analysed through in-situ SAXS. Both processing and chemical
      parameters are critical to obtain meso-organised spheres.

PMID- 14651111
TI  - Total synthesis of (-)-raumacline.
AB  - The total synthesis of (-)-raumacline from L-tryptophan was achieved, featuring a
      cis-specific Pictet-Spengler reaction, a stereoselective Dieckmann cyclization,
      and an epimerization step that allowed complete stereocontrol of five chiral
      centres.

PMID- 14651113
TI  - Pore size effects in the pyrolysis of 1,3-diphenylpropane confined in mesoporous
      silicas.
AB  - A new method for derivatizing mesoporous silicas, SBA-15 and MCM-41, with a
      substituted phenol is described, and pore confinement and surface curvature are
      shown to impact the reaction rate and product selectivity for the pyrolysis of
      surface-immobilized 1,3-diphenylpropane.

PMID- 14651112
TI  - Facilitation of addition-elimination reactions in pyrimidines and purines using
      trifluoroacetic acid in trifluoroethanol.
AB  - SNAr displacement reactions of 6-cyclohexylmethoxy-2-fluoropurine, 6-amino-2
      butylsulfonyl-4-cyclohexylmethoxypyrimidine and 2-amino-6-chloropurine with
      substituted anilines (e.g. the weakly nucleophilic 4-aminobenzenesulfonamide) are
      dramaticallyaccelerated in the presence of trifluoroacetic acid and occur
      especially efficiently in 2,2,2-trifluoroethanol solvent.

PMID- 14651114
TI  - Heterogeneous Baylis-Hillman using a polystyrene-bound 4-(N-benzyl-N
      methylamino)pyridine as reusable catalyst.
AB  - An insoluble Merrifield type resin having 4-aminopyridine units is a suitable and
      reusable heterogeneous catalyst for the Baylis-Hillman coupling of aromatic
      aldehydes and alpha,beta-unsaturated ketones.

PMID- 14651115
TI  - Observation of the enhancement in enantioselectivity with conversion for the
      aziridination of styrene using copper bis(oxazoline) complexes.
AB  - During the aziridination of styrene using copper bis(oxazoline) complexes the ee
      increases with conversion due to further reactions of the product.

PMID- 14651116
TI  - Direct photomodulation of peptide backbone conformations.
AB  - Significant photoswitching ability is found for secondary thioxopeptide bonds and
      can be used for the photomodulation of the backbone conformation of peptides or
      proteins.

PMID- 14651117
TI  - Aromatic nitrations in ionic liquids: the importance of cation choice.
AB  - Aromatic substrates can be nitrated in high yields and with efficient use of the
      nitrating agent in ionic liquids, although a suitably inert ionic liquid cation
      must be used.

PMID- 14651118
TI  - Ir/SiO2 as a highly active catalyst for the selective reduction of NO with CO in
      the presence of O2 and SO2.
AB  - Coexisting SO2 considerably enhanced the catalytic activity of Ir/SiO2 for NO
      reduction with CO in the presence of O2 because of the formation of a cis-type
      coordinated species of NO and CO to one iridium atom ([formula: see text]), a
      possible reaction intermediate leading to N2 formation.

PMID- 14651119
TI  - Ethylene trimerization with a half-sandwich titanium complex bearing a pendant
      thienyl group.
AB  - A half-sandwich titanium complex with a pendant thienyl group, activated by
      methylalumoxane (MAO), can trimerize ethylene to 1-hexene with considerable
      activity and high selectivity; the coodination of the sulfur atom to the titanium
      center is proposed to be responsible for the selective trimerization of ethylene.

PMID- 14651120
TI  - A novel electrochemical strategy for developing alkaline air electrodes by a
      combined use of dual functional catalysts.
AB  - A novel electrochemical strategy for the development of new alkaline air
      electrodes has been proposed based on a combined use of dual catalysts for redox
      mediating O2 reduction and disproportionating the reduction intermediates, i.e.,
      superoxide and peroxide in alkaline media.

PMID- 14651121
TI  - Cross-coupling reaction of thermally stable titanium(II)-alkyne complexes with
      aryl halides catalysed by a nickel complex.
AB  - The first cross-coupling reaction of thermally stable titanium(II)-alkyne
      complexes with aryl iodides in the presence of a catalytic amount of Ni(cod)2 is
      presented.

PMID- 14651122
TI  - Identification using LC-MSn of co-metabolites in the biosynthesis of the
      polyketide toxin mycolactone by a clinical isolate of Mycobacterium ulcerans.
AB  - LC-MSn analysis of mycolactone toxin from extracts of Mycobacterium ulcerans has
      shown that minor co-metabolites, including two previously unreported, differ
      structurally from mycolactone only in a small portion of the polyketide side
      chain.

PMID- 14651123
TI  - Molecular recognition. Self-assembly of molecular trigonal prisms and their host
      guest adducts.
AB  - Two supramolecular trigonal prisms, each bearing three molecular clefts are shown
      to form 1:6 and 1:7 host-guest complexes with 9-methylanthracene and one of the
      prisms forms a 1:2 host-guest complex with a tritopic tri-anthracene guest that
      registers with the recognition sites of the host.

PMID- 14651124
TI  - A new class of C1-symmetric monosulfoximine ligands for enantioselective hetero
      Diels-Alder reactions.
AB  - Quinoline-based C1-symmetric sulfoximines have been used as chiral ligands in
      copper-catalyzed asymmetric hetero Diels-Alder reactions leading to cycloadducts
      with up to 96% ee.

PMID- 14651125
TI  - Applying reversible chemistry of CO2 to supramolecular polymers.
AB  - Novel supramolecular, reversibly formed polymers featuring self-assembling
      capsules have been constructed through chemical fixation of CO2 and hydrogen
      bonding.

PMID- 14651126
TI  - Controlled crystallization of mixed-ligand complexes of 1,3-bis(4-pyridyl)propane
      N,N'-dioxide with metal(II) thiocyanates: isostructurality in coordination
      networks bearing different mono- and di-nuclear nodes.
AB  - The new flexible spacer ligand 1,3-bis(4-pyridyl)propane-N,N'-dioxide forms three
      classes of isomorphous compounds with metal(iI) thiocyanates at controlled ligand
      metal molar ratios, and its mu3-O,O,O' mode leads to a pair of coordination
      networks having the same (4, 4) topological characteristics but different mono-
      and di-nuclear nodes.

PMID- 14651127
TI  - Substrate specificity for catalysis of phosphodiester cleavage by a dinuclear
      Zn(II) complex.
AB  - The 2.4 kcal mol(-1) greater stabilization of the transition state for cleavage
      of the minimal substrate HpPNP compared to the nucleoside substrate UpPNP by the
      efficient dinuclear metal ion catalyst Zn2(L2O) provides evidence that access to
      the cationic core of Zn2(L2O) is sterically blocked for the bulkier nucleoside
      substrates, a flaw that will need to be dealt with in later generations of metal
      ion catalysts of RNA cleavage.

PMID- 14651128
TI  - Refinement of hydrogen atomic position in a hydrogen bond using a combination of
      solid-state NMR and computation.
AB  - DFT computations of the proton chemical shift for the intermolecular hydrogen
      bond in the white form of methylnitroacetanilide, together with the experimental
      value obtained by high-speed magic-angle spinning NMR, enable the N-H distance to
      be determined as 1.03 +/- 0.02 A.

PMID- 14651129
TI  - Alkoxyphenyl-substituted polyfluorene: a stable blue-light-emitting polymer with
      good solution processability.
AB  - A new alkoxyphenyl-substituted poly(fluorene) was synthesized to suppress the
      emission of long-wavelength radiation. The polymer emitted pure blue light, the
      characteristics of which did not change upon thermal annealing or normal
      operation of the EL device.

PMID- 14651130
TI  - Competitive electron transfers from a tyrosyl side-chain and peptide bond in the
      photodegradation of N-tosyl alpha-aminomethylamides: an insight into
      photosynthesis and photodamage in the biological oxidation of water?
AB  - Photo-excited N-tosyl derivatives of phenylalanyl- and, more particularly, O
      methyltyrosylmethylamides undergo electron transfer from aryl to tosyl groups
      whereas the photo-degradation of aliphatic analogues is initiated by electron
      transfer from the peptide bond, suggesting the latter as one possible reason for
      the rapid turnover of the D1 protein in biological water oxidation when the
      essential mediating role of tyrosine 116 in the PSII complex is inhibited.

PMID- 14651131
TI  - Effects of base pairing on the one-electron reduction rate of cytosine.
AB  - Using nucleoside derivatives, which are soluble in dichloromethane, we have
      experimentally demonstrated that the reduction potential of cytosine is lowered
      by base pairing with guanine.

PMID- 14651132
TI  - Diagnosis of kala-azar--an important stride.

PMID- 14651133
TI  - Sub clinical diabetes--vascular threat to Asian Indians.

PMID- 14651134
TI  - K39 strip test--easy, reliable and cost-effective field diagnosis for visceral
      leishmaniasis in India.
AB  - OBJECTIVE: A firm diagnosis of visceral leishmaniasis (VL) requires demonstration
      of the parasite in splenic or bone marrow aspirate. The aim of this prospective
      study was to assess the usefulness of K39 strip test as a noninvasive method of
      diagnosing visceral leishmaniasis under field conditions by testing serum
      antibody to the leishmanial antigen K39. MATERIAL AND METHODS: One drop of
      serum/blood was applied to the sample application pad on the test strip, which
      was diluted with 2 drops of chase buffer solution. The development of two visible
      red lines indicates the presence of IgG anti-K39. In the first phase of the study
      (2001), a total of 200 patients (Active VL-70, ex-VL-30, healthy endemic control
      20 and patients with other tropical diseases-80) were tested with the K39 strip
      test at the School of Tropical Medicine, Kolkata. In the second phase of the
      study (2002), the test was applied in a remote tribal area of West Bengal where
      an epidemic of VL had occurred. Thirty-two patients were identified in 207
      villagers of the affected area; all of them were tested with the K39 strip test.
      RESULTS: In the first phase, all VL and ex-VL cases gave positive results (100%).
      Ten percent of the healthy endemic controls were positive. The test results were
      negative in all other prevalent tropical diseases (100%). The estimated
      sensitivity of the test was 100% and the specificity was 98.18%. In the second
      phase of the study, all 32 patients of the epidemic were shown to be positive.
      All patients were treated with sodium stibogluconate injections and they
      recovered uneventfully. CONCLUSIONS: K39 strip test is ideal for rapid reliable
      field diagnosis of visceral leishmaniasis. The test has high sensitivity and
      specificity but it remains positive long after treatment (up to 3 years).

PMID- 14651135
TI  - Age-specific prevalence and risk associations for impaired glucose tolerance in
      urban southern Indian population.
AB  - OBJECTIVES: A national survey of diabetes and impaired glucose tolerance (IGT)
      conducted in 2000 AD in six major cities of India showed a high prevalence of
      diabetes (12.1%) and IGT (14%). Prevalence of IGT was higher than that of
      diabetes in subjects with less than 40 years when compared with older subjects.
      This analysis was done to look for differences in the risk factors associated
      with IGT in the younger and older subjects. METHODS: Associations of body mass
      index (BMI), waist : hip ratio, physical activity, family history of diabetes and
      monthly income with IGT and with diabetes were tested in the age groups of < 40
      and > or = 40 years separately. Multiple logistic regression analyses were done
      to test the associations. RESULTS: Prevalence of IGT was higher than diabetes in
      the younger group (13.1% Vs 5%, P < 0.001). Prevalence of obesity was higher in
      the older IGT subjects (38% Vs 30.5%, p < 0.003). Presence of positive family
      history of diabetes was similar in both the groups. In the > or = 40 year group
      age, BMI and family history of diabetes were common risk factors for diabetes and
      IGT. In the younger group, only BMI showed an association with IGT. The
      association of family history of diabetes with IGT was weaker than for diabetes
      even in the older subjects (Odds Ratio (OR) = 3.5 for diabetes, 1.33 for IGT).
      CONCLUSIONS: Prevalence of IGT was higher than diabetes in the age group < 40
      years. Only BMI showed an association with IGT in them while the risk
      associations were similar to diabetes in the older group. Prospective studies
      will throw more light on the implications of these findings.

PMID- 14651136
TI  - Glucose intolerance (diabetes and IGT) in a selected South Indian population with
      special reference to family history, obesity and lifestyle factors--the Chennai
      Urban Population Study (CUPS 14).
AB  - AIM OF THE STUDY: The aim of the study was to assess the impact of family history
      of diabetes, obesity and lifestyle factors particularly physical activity on
      glucose intolerance in a selected south Indian population. MATERIALS AND METHODS:
      The Chennai Urban Population Study (CUPS) is an epidemiological study involving
      two residential areas in Chennai in South India representing the middle and lower
      socio-economic group. Of the total of 1399 eligible subjects (age > or = 20
      years), 1262 (90.2%) participated in the study. A detailed questionnaire was used
      to collect details on medical history, family history of diabetes, family income
      and physical activity. All the study subjects underwent a glucose tolerance test
      (GTT) and were categorized as having normal glucose tolerance (NGT), impaired
      glucose tolerance (IGT) or diabetes using WHO consulting group criteria. Obesity
      and abdominal obesity were defined using the new Asia Pacific guidelines.
      RESULTS: The overall prevalence of diabetes in the study population was 12.0%,
      (age-standardized -9.3%), which included 7.2% of known diabetic subjects and 4.8%
      undiagnosed diabetic subjects, while the prevalence of impaired glucose tolerance
      was 5.9% (age-standardized prevalence 5.0%). The prevalence of glucose
      intolerance (Diabetes + IGT) was significantly higher among subjects with both
      parents diabetic (55%) compared to those with one parent diabetic (22.1%, p =
      0.005) and those with no family history (15.6%, p < 0.0001). Prevalence of
      glucose intolerance was significantly higher among subjects who had light grade
      physical activity (23.2%) compared to moderate (17.5%, p = 0.04) and heavy grade
      activity (8.1 % p < 0.00001). Subjects belonging to higher socio-economic status
      (SES) and who also had a positive family history of diabetes had five times
      greater prevalence of glucose intolerance compared to subjects from lower
      socioeconomic status and no family history (p < 0.0001). Regression analysis
      revealed age (p < 0.0001), waist circumference (p < 0.0001), body mass index (p <
      0.0001), waist-hip ratio (p < 0.0001), systolic blood pressure (p < 0.0001),
      diastolic blood pressure (p < 0.0001), family history of diabetes (p < 0.0001),
      higher SES (p < 0.0001), moderate (p = 0.001) and light (p < 0.001) grade
      physical activity to be associated with glucose intolerance. Multiple logistic
      regression analysis showed that even after adjusting for variables like age and
      family history of diabetes, physical activity showed a significant association
      with glucose intolerance CONCLUSION: The prevalence of glucose intolerance is
      high in this selected urban south Indian population. Lifestyle factors and family
      history have a synergistic effect on increasing the risk for diabetes in this
      population.

PMID- 14651138
TI  - Restless legs syndrome: diagnosis and treatment.
AB  - AIM: To describe clinical, biochemical and electrophysiological profile in Indian
      patients with Restless Legs Syndrome. MATERIAL AND METHODS: A total of 84
      patients with sleep disorders were evaluated. Eight patients were diagnosed to
      have RLS. All underwent series of hematological, biochemical investigations and
      electrophysiological studies. Severity was assessed before and after specific
      treatment RESULTS: Eight patients presenting with clinical features of RLS formed
      the study group. The mean age was 51.6 +/- 13.8 years. The male : female ratio
      was 7:1. Six cases were primary and two were of secondary type of RLS. Seven
      patients reported significant improvement in symptoms after treatment CONCLUSION:
      RLS can be diagnosed purely on clinical criteria; and appropriate treatment
      results in significant relief. Thus, the recognition of this entity is essential.

PMID- 14651137
TI  - HLA class II genotyping in chronic hepatitis B infection.
AB  - OBJECTIVES: To analyze the role of HLA genotypes in persistence of chronic
      hepatitis B in Western India. METHODS: HLA genotyping for class II-DR was done in
      26 subjects having chronic hepatitis B infection (HBsAg positive) and in 100
      healthy controls. Statistics were done using Halden's modification of Woolf's
      formula. RESULT: Significant association of chronic hepatitis B infection was
      found for class II-DR antigens DRB1*15XX (57.6 vs. 25%) and DRB1*11XX (23 vs.
      4%). DRB1*13XX (0 vs. 19%) was negatively associated with chronic hepatitis B
      infection. CONCLUSION: HLA phenotype, which varies with different regions, is one
      of the factors in persistence of hepatitis B infection. Our study supports
      negative association of DRB1*13XX to persistence of HBV. Also there may be role
      of DRB1*11XX and DRB1*15XX in persistence of HBV and development of chronic HBV
      hepatitis.

PMID- 14651139
TI  - Apolipoprotein E polymorphism and coronary heart disease.
AB  - Apolipoprotein E is a constituent of various lipoproteins and plays an important
      role in the transport of cholesterol and other lipids among cells of various
      tissues. The gene is polymorphic with three alleles (epsilon2, epsilon3, and
      epsilon4) coding for isoforms E2, E3, and E4 and having different binding
      affinities for the apo E receptors. While the epsilon2 allele is associated with
      elevated triglyceride levels, epsilon4 allele is associated with increased
      cholesterol levels. Though several studies support the role of apo E polymorphism
      in CHD either directly or indirectly via its influence on lipid and lipoprotein
      levels, there are some studies, which show no association. With the increasing
      incidence of CHD among Indians, it becomes imperative to identify genetic markers
      that may predispose individuals to coronary events. It would be of importance to
      determine if apo E gene will become a usefuladjunct to assess cardiovascular risk
      profile when performing genetic studies in families.

PMID- 14651140
TI  - Medical philaely (medical personalities on stamps). "G. Vianna and the parasite".

PMID- 14651141
TI  - HIV-associated dementia and caudate atrophy.

PMID- 14651142
TI  - Rhodotorula rubra.

PMID- 14651143
TI  - Etiopathophysiology of disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) involves activation of clotting as
      well as fibrinolytic pathways. Thrombosis from thrombin release results in end
      organ damage, whereas consumption of coagulation factors results in bleeding.
      Sepsis is the commonest cause of DIC. The consumption of antithrombin in sepsis
      abrogates its anti-inflammatory role and so its low level is a poor prognostic
      marker in sepsis. The increased release of plasminogen activator inhibitor-1 (PAI
      1) as seen in sepsis decreases fibrinolysis and promotes increased microvascular
      thrombosis. Here, we discuss the role of inhibitors of coagulation, cytokines,
      kinins, complement and vasoactive peptides in DIC.

PMID- 14651144
TI  - Gastrointestinal stromal tumour--a paradigm shift in management of solid tumours.
AB  - Gastrointestinal stromal tumour (GIST) till recently were non-responsive to all
      chemotherapy agents. With the advent of c-kit, diagnosis of GIST has become more
      specific. STI-571, a tyrosine kinase, has become one of the first targeted
      therapeutic agent tobe active in solid tumour. At present it is the only agent
      with substantial activity in GIST.

PMID- 14651145
TI  - Neurally-mediated syncope: an overview and approach.

PMID- 14651146
TI  - Woman, moon and menstruation.

PMID- 14651147
TI  - Olivopontocerebellar atrophy presenting with stridor.
AB  - The spectrum of degenerative ataxia includes the symptomatic degenerative ataxias
      and the primary degenerative ataxias. The later may be sporadic and idiopathic or
      hereditary, being genetically determined. When an individual ataxic patient
      presents with an adult-onset degenerative ataxia and has a negative family
      history, the physician is faced with a diagnosis of pure idiopathic sporadic
      degenerative ataxia or one of the hereditary ataxias. The clinical spectrum of
      olivopontocerebellar atrophy (OPCA) usually consists of pancerebellar signs with
      pyramidal and abnormal eye movements. Although Stridor is more commonly found in
      multisystem atrophy, it is rarely seen in OPCA. We, here report a case of third
      decade onset of ataxia presenting with stridor.

PMID- 14651148
TI  - Rodenticide-induced hepatotoxicity.
AB  - Hepatotoxicity following acute poisoning with rodenticides has been infrequently
      reported in literature. To emphasize the fact that this form of clinical
      presentation is not unusual we are reporting two cases of rodenticide poisoning
      masquerading as severe hepatic dysfunction.

PMID- 14651149
TI  - Amlodipine-induced gingival hyperplasia.
AB  - Gingival hyperplasia can occur during use of drugs such as diphenylhydantoin,
      cyclosporine and nifedipine. We report, three cases of gingival hyperplasia
      induced by amlodipine, a second generation calcium channel blocker. Exact cause
      of induction of thehyperplasia is not known. Individual variation in metabolism
      of the drug may be a factor.

PMID- 14651150
TI  - Syringomyelia in caudal dysplasia sequence.
AB  - Caudal dysplasia sequence (CDS) comprises developmental anomalies of the caudal
      vertebrae, neural tube, urogenital and digestive organs, and hind limbs, the
      precursors of all of which are derived from the caudal eminence. Although the
      syndrome is well recognized, the etiology and pathogenetic mechanisms are poorly
      understood. We report syringomyelia in association with the CDS, which has not
      been described previously and recommends inclusion of this entity in the spectrum
      of abnormalities encountered in this syndrome.

PMID- 14651151
TI  - Cholangiocarcinoma presenting with recurrent venous thrombosis.
AB  - A 38 years female presented with three episodes of venous thrombosis over one
      year--first in left femoral vein, next in splenic vein causing haematemesis and
      malena and lastly in inferior vena cava causing Budd-Chiari syndrome. During
      third episode, endoscopic cholangiopancreatography and guided biopsy established
      a diagnosis of cholangiocarcinoma at the mid portion of common bile duct. The
      disease was far advanced with cervical lymph node metastasis.

PMID- 14651152
TI  - Gigantism associated with slipped capital femoral epiphysis.
AB  - The etiology of slipped capital femoral epiphysis (SCFE) is unknown, though
      hormonal as well as mechanical factors have been implicated. We report a case of
      gigantism who presented with SCFE. This case provides an insight into the genesis
      of SCFE, which in this case was related to growth hormone excess and sex-hormone
      deficiency.

PMID- 14651153
TI  - Bilateral ptosis following wasp sting.
AB  - We report a case of bilateral ptosis due to wasp sting which was completely
      treatable.

PMID- 14651154
TI  - Isolated extra-cranial internal carotid artery aneurysm in a young adult with
      Eale's disease.
AB  - A young male patient, a known case of Eale's disease presented with a large
      isolated aneurysm of the extra-cranial part of internal carotid artery. Detailed
      investigation failed to establish the etiology of the aneurysm, and it is
      possible that the underlying pathology may be the same as that of Eale's disease.
      Eale's disease is an idiopathic vascular disease of the peripheral retina and we
      hypothesize that aneurysm in this patient may be associated with Eale's disease
      of the eye.

PMID- 14651155
TI  - Spontaneous autoamputation and expulsion of intestinal lipoma.

PMID- 14651156
TI  - Hodgkin's disease and pilocytic astrocytoma--a synchronous presentation.

PMID- 14651157
TI  - Torsade de pointes probably induced by sparfloxain.

PMID- 14651158
TI  - Air pollution.

PMID- 14651159
TI  - Paroxysmal nocturnal movements secondary to obstructive sleep apnoea syndrome.

PMID- 14651160
TI  - Possible application of milk oligosaccharides for drug development.
AB  - By applying a finger-printing method to the analysis of human milk
      oligosaccharides, several oligosacchartides were found to be deleted in the milk
      of non-secretor or Lewis negative individual. This finding afforded a clue to
      elucidate the enzymatic basis of blood types in humans. Furthermore,
      disappearance of some major oligosaccharides led to the finding of five novel
      minor oligosaccharides, which were hidden under the major oligosaccharides. Later
      on, structures of more than seventy oligosaccharides were elucidated. These
      oligosaccharides are derived from eleven core oligosaccharides by sialylation
      and/or fucosylation. All these oligosaccharides contain lactose at their reducing
      termini. This evidence, together with the deletion phenomena found in the milk of
      two blood type individuals, suggested that the oligosaccharides are formed by the
      concerted action of glycosyltransferases, which are responsible for formation of
      the sugar chains of glycoproteins on the surface of epithelial cells constructing
      the mucous membrane. The elongation may start by the action of iGnT. This enzyme
      is responsible for the addition of a beta-N-acetylglucosamine residue to the C-3
      position of the galactose moiety constructing the N-acetyllactosamine group of
      the sugar chains of glycoconjugates. Therefore, oligosaccharides in human milk
      may include many structures, starting from the N-acetyllactosamine residues in
      the sugar chains of various glycoproteins. Many evidences, which indicate that
      virulent enteric bacteria and viruses start their infection by binding to
      particular sugar chains of glycoconjugates on the surface of their target cells,
      were presented recently. Therefore, milk oligosaccharides are expected to be
      useful to inhibit the infection of these bacteria and viruses.

PMID- 14651161
TI  - Lack of correlation of betel nut chewing, tobacco smoking, and alcohol
      consumption with telomerase activity and the severity of oral cancer.
AB  - BACKGROUND: Oral cancer is one of the most frequent cancers. A strong association
      has been found between oral cancer incidence and the use of betel nut, alcohol,
      and tobacco. Telomerase activity (TA) has also been shown to play a role in
      carcinogenesis. We therefore surveyed the consumption habits of betel nut
      chewing, alcohol drinking, and tobacco smoking in oral cancer patients and
      evaluated the association of these habits with TA level and clinical stage.
      METHODS: In total, 154 oral cancer patients were recruited. TA was measured in
      paired (grossly normal and cancerous) tissues using a polymerase chain reaction
      based enzyme immunoassay. Associations of these factors with clinical stage and
      TA level were analyzed using the Pearson chi-square test. RESULTS: In these
      patients, 86.4%, 61.0%, and 83.3% used betel nut, alcohol, and tobacco,
      respectively. For all tissue assayed, 80.5% of cancerous and 3.2% of grossly
      normal mucosae were positive for TA. However, neither clinical stage nor TA level
      in cancerous tissues had a statistical association with the use of individual
      substances (betel nut, alcohol, and tobacco) or their combined use. CONCLUSION:
      Even though the habitual uses of these substances have been previously reported
      to be associated with oral cancer incidence, we found a lack of correlation with
      TA level or with disease severity in our study. These results imply that these
      consumption habits might only be associated with the early stages of oral cancer
      development, while the later stages of cancer progression may be more associated
      with other external factors or dependent on host cellular factors, all of which
      require confirmation through further investigations.

PMID- 14651162
TI  - Postoperative adjuvant radiotherapy for adenoid cystic carcinoma of the head and
      neck: treatment results and prognostic factors.
AB  - BACKGROUND: To analyze the treatment results and prognostic factors of patients
      with adenoid cystic carcinoma (ACC) arising from the major and minor salivary
      glands of the head and neck, and who received postoperative radiotherapy after
      radical tumor resection. METHODS: Between October 1987 and December 1999, 25
      patients with ACC of the head and neck were treated with radical surgical
      resection and postoperative adjuvant irradiation without chemotherapy. Using
      appropriate radiation techniques to the tumor bed, total doses ranged from 44 to
      68.4 Gy. All patients had a minimum of 2 years of follow-up. RESULTS: The 5-year
      overall survival rate, local control rate, and distant metastasis-free rate were
      75%, 83%, and 66%, respectively. To the present, 2 patients had experienced
      recurrence at the primary sites, and 1 had regional lymph node metastasis.
      Distant metastases developed in 7 patients (28%), of whom 6 (86%) were disease
      free at the primary site. The lung was the most common distant metastatic site.
      In multivariate analysis, the only statistically significant prognostic factor
      for a distant metastasis-free rate was the stage at presentation (p = 0.009).
      CONCLUSION: Patients with an advanced stage of disease had higher distant
      metastasis rates even when receiving postoperative radiotherapy. Distant
      metastasis is still the main problem in the management of ACC of the head and
      neck. However, more-effective treatment for this problem is still lacking.

PMID- 14651163
TI  - Rotavirus gastroenteritis associated with afebrile convulsion in children:
      clinical analysis of 40 cases.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical manifestations
      and outcomes of hospitalized children with afebrile seizures following rotavirus
      gastroenteritis. METHODS: We conducted a retrospective study enrolling patients
      under 18 years old who were admitted to our hospital during a 10-year period with
      the diagnosis of rotavirus gastroenteritis. We identified and further analyzed
      patients who presented with afebrile seizures, without previous seizure
      disorders, electrolyte imbalances or hypoglycemia. The statistical methods used
      were the Chi-square test, the Kruskal-Wallis test and the Mann-Whitney test.
      RESULTS: Of 1937 patients, 40 patients (24 female and 16 male patients) met the
      inclusion criteria. The incidence of afebrile seizures following rotavirus
      gastroenteritis was 2.06%. The age of the patients ranged from 6 months old to 6
      years old (mean, 1.9 years). The highest incidence of afebrile seizures was 4.67%
      in children 1 to 2 years of age (p < 0.001). Twenty-seven patients (67.5%) had
      two or more seizures, which usually were in clusters within a 24-hour period. No
      status epilepticus was observed. More than half of the patients (52.5%) suffered
      from seizures on the third day of diarrhea. Only five of 35 patients showed
      abnormal electroencephalogram (EEG) findings, which reverted to normal in four of
      the patients during the follow-up period. Most patients did not require long-term
      anticonvulsant treatment. During the follow-up period, all patients displayed
      normal psychomotor development without the recurrence of seizures, except in one
      patient who had a febrile convulsion. CONCLUSION: We found that the course of
      afebrile seizures following rotavirus gastroenteritis was benign with
      satisfactory outcomes.

PMID- 14651165
TI  - Malignant hypertensive retinopathy-clinical and fundus manifestations in patients
      with new onset or acute exacerbation of chronic hypertension.
AB  - BACKGROUND: We attempted to review the clinical and fundus findings in patients
      with malignant hypertension (MHT). METHODS: Charts and fundus photographs of
      patients with malignant hypertensive retinopathy from 1995 to 2000 were
      retrospectively reviewed. Data of patients were included when their color fundus
      photographs revealed findings suggestive of malignant hypertension (MHT). There
      had to have been at least 1 high blood pressure reading recorded in the chart
      during the period when the symptoms occurred. Data were excluded from patients
      with diseases such as diabetes mellitus, blood dyscrasia, and autoimmune and
      infectious diseases which can mimic the fundus findings of MHT. RESULTS: Fourteen
      patients were included in our study. Patients were divided into 2 groups
      according to whether or not they had a history of hypertension. Group 1 included
      6 patients with no hypertension history, while group 2 included 8 patients with a
      known hypertension history. In group 1, MHT was diagnosed by an ophthalmologist
      in 4 patients, and the other 2 patients were referred from the Gynecology and
      Nephrology Departments. Between the 2 groups, there were no significant
      differences in age, or systolic and diastolic blood pressures. There were more
      complications such as renal failure and stroke in group 2 patients. CONCLUSION:
      Funduscopy has decisive significance in the diagnosis and monitoring of MHT. In
      order to accurately diagnose and achieve early control of this critical
      condition, a detailed fundus examination and blood pressure monitoring are
      mandatory.

PMID- 14651164
TI  - Mini-open intramedullary nailing of acute femoral shaft fracture: reduction
      through a small incision without a fracture table.
AB  - BACKGROUND: Femoral shaft fractures are usually treated with intramedullary
      nailing. In this study, we report on a modified surgical technique with reduction
      through a small incision for this type of fracture. METHODS: From 1994 to 1997,
      this technique was used on 74 patients with 82 femoral shaft fractures. Seventy
      patients (76 fractures) with at least 3 years of postoperative follow-up were
      included for clinical evaluation. The surgical technique involves a mini-wound at
      the fracture site, and fracture reduction is performed with 1 finger or a bone
      hook without the use of a fracture table. RESULTS: Seventy-four fractures (97%)
      healed in the first 6 months. In 2 patients, there was little evidence of
      fracture union at 6 months. One of these 2 patients was treated with an open bone
      graft, and the other was treated with a closed exchanging nail. Finally these 2
      patients healed. The mean operation time for this procedure was 75 minutes.
      CONCLUSION: The advantages of this procedure include that no fracture table is
      needed, there is a shorter operation time, there is a small amount of blood loss,
      and it is especially suitable for multiple trauma patients.

PMID- 14651166
TI  - Management of talon cusp affecting the primary central incisor: a case report.
AB  - Talon cusps are relatively rare dental anomalies that manifest as accessory
      cusplike structures and project from the cingulum area of the anterior teeth. The
      condition can occur in both the primary and permanent dentitions. However, the
      occurrences of anomalous cusps are rather infrequent in the primary dentition.
      Little has been written about the treatment of talon cusps in the primary
      dentition compared with their counterparts in the permanent dentition. The
      purpose of this article was to document the management of a patient with a
      maxillary primary incisor affected by a talon cusp and the long-term follow up.

PMID- 14651167
TI  - Guided bone regeneration for fenestration defects in dental implants.
AB  - Guided bone regeneration has been applied in implant dentistry for increasing the
      width and height of the alveolar ridge in areas with insufficient bone. Various
      materials and techniques have been used for this purpose. It refers to a surgical
      procedure by which utilizing a mechanical barrier to create a secluded space
      around the defect to permit bone regeneration without the competition of other
      tissues. This report presents a case with buccal fenestrations on maxillary
      implant sites observed during a surgical procedure. An allograft and a non
      resorbable membrane were concomitantly used to increase the width of the alveolar
      ridge. Hard tissue regeneration was evident clinically. The implants were
      restored for functioning and followed for 2 years. Factors affecting outcomes are
      also discussed. Membrane stability and the space-making effect remain the keys to
      success.

PMID- 14651168
TI  - Pneumolabyrinth associated with perilymph fistula.
AB  - Pneumolabyrinth associated with perilymph fistula, especially with the presence
      of air in the cochlea, has rarely been identified using imaging study. We present
      a 24-year-old woman who experienced right fluctuating sensorineural hearing
      impairment and dis-equilibrium after sustaining an open-handed slap on the right
      side of her face. The diagnosis of pneumolabyrinth was established through the
      detection of air bubbles in the right basal turn of cochlea using high-resolution
      computerized tomography. Right side exploratory tympanotomy confirmed the
      presence of a perilymph fistula. The patient was free of symptoms after surgery.
      Early fistula repair was beneficial in this case.

PMID- 14651169
TI  - Ovarian endometrioma associated with very high serum CA-125 levels.
AB  - CA-125 is a 220-kD cell surface glycoprotein present in over 80% of non-mucinous
      epithelial ovarian carcinomas and it occurs in the serum of healthy males and
      females at low concentrations (< 35 U/mL). Serum CA-125 concentration may also be
      moderately elevated in several benign conditions, such as pelvic inflammatory
      disease, uterine fibroids, pregnancy, spontaneous abortion with chromosomal
      abnormality, and especially in endometriosis. However, serum CA-125 concentration
      is seldom > 100 IU/ml in endometriosis. In this paper, we present a patient with
      unilateral ovarian endometrioma associated with abnormally high serum CA-125
      level (> 6000 U/mL) and after excision of the ovarian tumor, the CA-125 levels
      returned to normal. Our case further emphasizes the association of high levels of
      CA-125 with benign gynecologic conditions and we discussed the possible
      explanations for this abnormal elevation of CA-125 levels.

PMID- 14651170
TI  - Alobar holoprosencephaly: report of two cases with unusual findings.
AB  - Holoprosencephaly, a disorder resulting from failure of cleavage or incomplete
      differentiation of the forebrain structures at various levels or to various
      degrees, is related to hereditary factors, chromosomal anomalies, cytogenetic
      abnormalities, and environmental teratogenic factors. We report on 2 cases of
      alobar holoprosencephaly, with similar physical findings, including microcephaly,
      microphthalmia, cebocephalus, choanal atresia, pseudo cleft palate, distended
      abdomen, and acrocyanosis. The brain echogram of these 2 patients demonstrated
      fused thalami and a single large U-shaped ventricular cavity. Chromosome studies
      of these 2 patients were normal. The findings of the autopsies confirmed the
      clinical presentations. One of our cases had a clinical picture similar to that
      of holoprosencephaly-polydactyly syndrome. The other had the rare anatomical
      finding of a polylobuated spleen. Because of the poor prognosis of alobar
      holoprosencephaly, early prenatal diagnosis is recommended.

PMID- 14651172
TI  - Introduction: queering communication: starting the conversation.

PMID- 14651173
TI  - The violence of heteronormativity in communication studies: notes on injury,
      healing, and queer world-making.
AB  - Heteronormativity is everywhere. It is always already present in our individual
      and collective psyches, social institutions, cultural practices, and knowledge
      systems. In this essay, I provide some sketches for a critical analysis of
      heteronormativity in the communication discipline. More specifically, I examine
      the symbolic, discursive, psychological, and material violence of
      heteronormativity, and begin exploring ways to heal, grow, transform, and
      contemplate new possibilities in our social world. To accomplish this, this essay
      is divided into live sections. First, I discuss the study of sexuality in
      Communication. Next, through the notion of injury, I focus on the violence of
      heteronormativity. Third, using the concept of healing, I discuss ways of
      unpacking heteronormativity through a critique of hegemonic heterosexuality.
      Further, I offer potential ways for queer world-making through the lens of queer
      theory. I conclude by exploring the need for more sexuality research in the
      discipline by engaging the productive tensions between constructive and
      deconstructive impulses.

PMID- 14651174
TI  - Queering relationships: toward a paradigmatic shift.
AB  - This article exposes, and is critical of, the blatant and insidious ways in which
      a specific brand of heterosexual relationship has been promoted as the ultimate
      relational form at the expense of others who neither believe in nor practice such
      idealized relationships. To uncover this multilayered and deeply imbedded
      ideology, this piece turns to a description and analysis of how various
      institutions (e.g., organized religion, medicine, education, law, politics, and
      the family) perpetuate heteronormative practices in general. Next, specific
      traits considered to constitute the best and most respectable relationship style
      are identified. Then, notions of how heteronormativity is marketed and reproduced
      to create a sexual relationship hierarchy--with a certain form of heterosexuality
      elevated to the top, as the most revered and cherished relational form--are
      described and analyzed. Turning to the results of such a well-established and
      entrenched "marketing campaign," the author offers some notes regarding attitudes
      about sexual relationships gleaned from teaching a course, "Sex and
      Relationships," for over a decade. Finally, the author explores the merits and
      potential drawbacks of a paradigmatic shift toward queering relationships and
      possible directions for theoretical interventions.

PMID- 14651175
TI  - Speaking to silence: toward queering nonverbal communication.
AB  - The majority of nonverbal communication research and pedagogy reproduces
      heterosexist and sexist ideologies, normalizing and naturalizing gender and
      sexual binaries, and sanctioning an exceedingly narrow range of gendered and
      sexualized subjects, practices, and relationships. This essay proposes that
      nonverbal communication scholarship and pedagogy need to address these issues.
      First, I provide a brief summary of the history of the field of nonverbal
      communication. Second, I critique the conspicuous absence of the queer subject,
      the rigid essentialism, and the pervasive heterosexism in nonverbal communication
      textbooks in particular. Finally, I discuss three examples of communication
      research that avoid these pitfalls and herald what queering nonverbal
      communication might look like.

PMID- 14651176
TI  - Racisms, heterosexisms, and identities: a semiotic phenomenology of self
      understanding.
AB  - This article examines the contributions of lesbians of color to the developmental
      relationship between queer theory and qualitative research methodology. Its
      thesis is that the contributions of lesbians of color in this context have been
      overlooked despite being featured. This oversight is explained through an
      examination of theoretical perspectives that dominate our current understanding
      of the relationship between queer theory and qualitative research. Postmodernism
      is revealed as susceptible to liberal bias and racist exclusions common in U.S.
      culture. Semiotic phenomenology is offered as a non-essentialist approach to
      queer theory and qualitative research that reduces the liberal bias and racist
      exclusions often perpetuated in postmodern theorizing that have led to the
      exclusion of contributions of lesbians of color in queer theory.

PMID- 14651177
TI  - Queer criticism and sexual normativity: the case of Pee-wee Herman.
AB  - One of the most useful aspects of queer theory is the critical force that the
      perspective provides scholars. The tenets of queer theory provide scholars with a
      model to interrogate how sexuality and other differences play a fundamental role
      in rhetorical practice. Focusing on differences rather than similarities, queer
      critics seek to dismantle hierarchies by blurring the definitions of specific
      identity categories. A framework for queer rhetorical criticism is described and
      illustrated with a variety of examples from popular culture. The model is further
      illustrated through an examination of the body of work of Pee-wee Herman.

PMID- 14651178
TI  - Kuaering queer theory: my autocritography and a race-conscious, womanist,
      transnational turn.
AB  - Critiquing queer theory's omissions in race and class, E. Patrick Johnson (2001)
      suggests "quare" studies, a turn similar to that being made from feminism to
      womanism. I fully embrace Johnson's theorizing. But to make relevant the worlds
      lying beyond the pale of North America, Europe, and the English language to the
      study of sexualities and other dimensions of systematic discrimination, I use
      kuaer theory to make another turn. One that is at once race-conscious, womanist
      and transnational. I travel through three awakenings, and look into nu nu (female
      female) words in Taiwanese and Chinese lesbian existence in different historical
      periods. I also ofter a rhetorical analysis of the title of Ai Bao, the first
      officially registered Taiwanese lesbian magazine, exploring its persuasiveness
      via wordplay and multiple entendre. In addition, from jin lan hui to nu tongzhi,
      from T/puo and lazi to kuer, I provide sketches of heterogeneous and complex
      Taiwanese and Chinese nu nu worlds. As I get deeper into my autocritography,
      these women become my women and I learn to utter my own words in a language that
      is little pre-packaged. My crossing marks a daring but humble beginning. If
      nothing else, there is at least more space for bringing up race and transnational
      complicity queerly.

PMID- 14651179
TI  - Immigrant closets: tactical-micro-practices-in-the-hyphen.
AB  - The theoretical and material moves within this essay suggest that culturally
      hybrid agents use the "closet" as a space to negotiate the intersections of
      sexuality and ethnicity in everyday life. Discussing some conclusions of my
      ethnographic research project with the Russian Gay and Lesbian Group of West
      Hollywood, this essay applies Michel de Certeau's notion of tactics to the daily
      micro-practices of queer identified immigrants as they move between the demands
      of overlapping and contradictory cultures. Examining the circumstances in the
      Russian-American-immigrant-imagined community shared by the informants in this
      site, I argue that, contrary to a popularized valorization of queer "outness,"
      there is a great deal of power in the oscillation between visibility and
      invisibility.

PMID- 14651180
TI  - Negotiating multiple identities in a queer Vietnamese support group.
AB  - My participant-observation with O-Moi, a support group for Vietnamese lesbians,
      bisexual women and female-to-male transgenders, and interviews with members,
      focusing on how different identity issues are negotiated, suggest that despite O
      Moi's claim of supporting its members' multiple marginalized identities, group
      processes in everyday pragmatic interactions construct a hierarchy that centers
      and normalizes experiences of bilingual Vietnamese lesbians. This renders the
      marginalization of bisexual women, transgender men, and Vietnamese/English
      monolingual members. Using the concept of "identity work" to examine the
      intersection of race/ethnicity, class, and gender/sexuality as everyday
      (counter)hegemonic processes, I discuss how organizational structure, discourse
      resources, and personal politics orient and mold members' talk and interactions
      leading to normalization and/or marginalization of certain groups' experiences.

PMID- 14651181
TI  - The specter of the black fag: parody, blackness, and hetero/homosexual
      B(r)others.
AB  - This essay investigates the ways in which three African American heterosexual
      males-Eddie Murphy, Damon Wayans, and David Alan Grier-appropriate signifiers of
      gayness to parody, stereotype, and repudiate black gay men. These performances
      are also attempts to circumscribe the boundaries of blackness, ultimately
      suggesting that "authentic" blackness is lodged within hegemonic black
      masculinity. Contrary to this desired effect, the essay demonstrates how these
      performers, in the act of repudiation, ironically and unwittingly queer
      heteronormative black masculinity, securing further the dialectic between
      heterosexuality and homosexuality. Finally, the essay argues that these
      performances manifest the black heterosexual male's melancholia, his refusal to
      grieve the loss of his sexual B(r)other.

PMID- 14651182
TI  - The queering of Swan Lake: a new male gaze for the performance of sexual desire.
AB  - This essay argues that, by re-gendering the ballet classic Swan Lake,
      choreographer Matthew Bourne has also queered it. He thrusts center stage an
      unstable relationship between two male characters, and in so doing, de-centers
      the conventionally fixed categories of sex, gender and sexual desire. He also
      forces a long-simmering relationship between homosexuality and dance out of the
      closet and into mainstream popular culture. Applying Mulvey's theory of
      spectatorship and Butler's theory of gendered performance, the essay describes
      how viewers may be intrigued, rather than repulsed, by the ambiguities
      surrounding Bourne's portrayal of sexual identity.

PMID- 14651183
TI  - Queering marriage: an ideographic interrogation of heteronormative subjectivity.
AB  - Recent debates on same-sex marriage mark the institution, practice, and concept
      of marriage as a significant site of power and resistance within American
      culture. Adopting Michel Foucault's conception of "discipline," this essay
      examines how marriage discourse reinforces heteronormative power relations
      through its rhetorical constitution of gay male identity. Supplementing
      "ideographic" critique with Judith Butler's theory of performative speech acts
      enables us to better interrogate and resist these operations of power. This essay
      maps the contemporary scene of heteronormative power and resistance through two
      rhetorical performances of gay male identity. The marriage debates, in the first
      instance, demonstrate how a conventional desire for masculine agency influences
      the heteronormative production of gay male identity. In the second instance, gay
      male SM [sadomasochism] performs a concept of "relational agency," which
      potentially resists heteronormativity.

PMID- 14651184
TI  - Transgender DeKalb: observations of an advocacy campaign.
AB  - In September 2000, the Community Members Against Discrimination (CMAD), a
      grassroots LGBT organization in DeKalb, Illinois, convinced their city council to
      add protection against discrimination on the basis of gender identity and
      expression. Written as an autoethnography, this essay considers the events of the
      campaign in terms of queer theory and the study of public argument by isolating a
      set of episodes that bring the reader closer to the experiences of transgender
      citizens who act in a public culture. The author also explores his own
      responsibilities as a scholar of communication, an activist, and a member of the
      LGBT community.

PMID- 14651185
TI  - Disciplining "Sextext": queers, fears, and communication studies.
AB  - This essay is a critical interrogation of disciplinary responses to Tom Nakayama
      and Fred Corey's 1997 Text and Performance Quarterly essay, "Sextext."
      Disciplinary responses to the essay suggest strong resistance to queer theory as
      a "legitimate" intellectual and critical framework. By reading the responses to
      "Sextext" through the lens of queer theory, and by offering a political reading
      of conventional studies of sexual representation, this essay suggests how
      disciplinary boundaries in Communication Studies are policed to protect the
      production of "legitimate" scholarship. By revealing these practices, this essay
      provides further support for the central value of queer theory to the discipline
      of Communication Studies.

PMID- 14651186
TI  - Nextext.
AB  - Gay men who are marked as "sexual outlaws" have unique and tense relationships
      with social regulatory forces, and for the porn star, the tensions are
      exacerbated. Surveillance, attraction, seduction, repulsion, authority, and
      discipline mark the communicative dynamics between the bodies of subject/object,
      performer/spectator, image-maker/imagined. This essay, which is a follow-up to
      "Sextext," is a fictional account of a porn star who navigates personal and
      social relationships in the context of a culture that averts overt discussions of
      carnal desire.

PMID- 14651187
TI  - Reflections on queer theory: disparate points of view.

PMID- 14651188
TI  - The normalization of queer theory.

PMID- 14651189
TI  - Queer theory, gay movements, and political communication.

PMID- 14651190
TI  - Querying queer theory again (or queer theory as drag performance).

PMID- 14651191
TI  - Queer theory and performance.

PMID- 14651192
TI  - Queer theory in education.

PMID- 14651193
TI  - Reflections on queer studies and queer pedagogy.

PMID- 14651194
TI  - Queer ideals in education.

PMID- 14651195
TI  - Sounds queer to me: the politics of disillusionment.

PMID- 14651196
TI  - Queer theory, new millennium.

PMID- 14651197
TI  - Run queer Asia run.

PMID- 14651198
TI  - Reflections on queer theory and communication.

PMID- 14651199
TI  - More queer: resources on queer theory.

PMID- 14651200
TI  - Liver metastases from colorectal cancer--more cures awaiting?

PMID- 14651201
TI  - New techniques and agents in the adjuvant therapy of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma represents a major oncological challenge.
      Despite improvements in surgical techniques, long-term survival after resection
      is poor, with few patients surviving after 5 years. Until recently, there have
      been no large randomized trials of adjuvant therapy in pancreatic ductal
      adenocarcinoma. However, major trials such as the European Study Group for
      Pancreatic Cancer (ESPAC-1) and ESPAC-3 trials have set new standards for patient
      recruitment and development in this field. Adjuvant therapy has the potential to
      improve both patient survival and quality of life after curative resection.
      Currently, the best treatment is with 5-fluorouracil with folinic acid, but in
      the light of ongoing clinical trials, this may be supplanted by gemcitabine as
      the treatment of choice. Chemoradiotherapy does not appear to be beneficial in
      the adjuvant setting, but trials of a wide variety of other techniques and agents
      in the treatment of advanced disease are being undertaken and some of these will
      almost certainly be extended into the adjuvant setting in time. Great progress
      has been made in the adjuvant treatment of pancreatic cancer in the past 10 years
      and similar advances are likely over the next decade.

PMID- 14651202
TI  - Swedish Cancer Society radiation therapy research investigation.
AB  - In an investigation by the Swedish Cancer Society, the present status, critical
      issues and future aspects and prospects were described by an expert group for
      each of nine major areas of radiation research. A summary of the investigation is
      presented in this report. A more extensive summary (in Swedish) can be found at
      www.Cancerfonden.se. It is concluded that radiation therapy plays an increasingly
      important role in curative and palliative tumour treatment and presents a
      considerable challenge to research. Several suggestions are made that could
      improve the possibilities for high-quality radiation therapy research in Sweden.

PMID- 14651203
TI  - Medical imaging for improved tumour characterization, delineation and treatment
      verification.
AB  - In an investigation by the Swedish Cancer Society, the present status, critical
      issues and future aspects and potentials were described by an expert group for
      each of nine major areas of radiation therapy research. This report deals with
      medical imaging for improved medical diagnosis including tumour detection,
      staging and characterization, treatment planning, guiding and verification,
      evaluation of response and treatment follow-up.

PMID- 14651204
TI  - Sensitizing and protective substances in radiation therapy and predictive assays.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. The present report deals with the
      use of sensitizing and protective substances in radiation therapy and predictive
      assays on normal tissues and tumour response.

PMID- 14651205
TI  - Therapy with radiopharmaceuticals.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. The present report deals with
      therapy with radiopharmaceuticals.

PMID- 14651206
TI  - Radiation therapy through activation of stable nuclides.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. This report deals with radiation
      therapy using activation of stable nuclides.

PMID- 14651207
TI  - Interactions between chemotherapy, endocrine therapy and radiation.
AB  - In an investigation by the Swedish Cancer Society, an expert group described the
      present status, critical issues and future aspects and potentials for each of
      nine major areas of radiation therapy research. This report deals with
      interactions between chemotherapy, endocrine therapy, other anti-tumour drugs and
      radiation.

PMID- 14651208
TI  - 'Patient satisfaction' in hospitalized cancer patients.
AB  - Predictors of 'patient satisfaction' with hospitalization at a specialized cancer
      hospital in Norway are examined in this study. Two weeks after their last
      hospitalization, 2021 consecutive cancer patients were invited to rate their
      satisfaction with hospitalization, quality of life, anxiety and depression.
      Compliance rate was 72% (n = 1453). Cut-off levels separating dissatisfied from
      satisfied patients were defined. It was found that 92% of the patients were
      satisfied with their stay in hospital, independent of cancer type and number of
      previous admissions. Performance of nurses and physicians, level of information
      perceived, outcome of health status, reception at the hospital and anxiety
      independently predicted 'patient satisfaction'. The model explained 35% of the
      variance with an area under the curve of 0.76 of the Receiver Operator Curve.
      Cancer patients' satisfaction with their hospital stay was high, and predicted by
      four independently predictive variables related to the performance of caregivers.
      These suggest areas for further improvement in the healthcare service.

PMID- 14651209
TI  - Use of alternative medicine among Norwegian cancer patients is associated with
      mental distress--a follow-up study.
AB  - The purpose of this study was to investigate the relationship between the use of
      alternative medicine (AM) by cancer patients' and the level of self-perceived
      mental distress. One hundred and fifty-seven cancer patients were included in a
      longitudinal questionnaire-based study 12 months after their first contact with
      the Department of Oncology, University Hospital of Tromso, during the period 1990
      to 1991. Eligible patients received follow-up questionnaires after 24 and 60
      months recording their use of AM and measuring their perceived mental distress
      (GHQ-20). A total of 64 (41%) of the 157 patients who completed at least one
      questionnaire reported using AM one or more times during follow-up (ever-use).
      Between 65% and 79% of patients who were eligible at each point of the study
      completed the GHQ questionnaire. After 60 months of follow-up, 104 patients were
      still alive and 54 patients (52% of the survivors) had completed all the
      questionnaires. At inclusion in the study, significantly more AM users reported
      mental distress (57%) than non-users (20%) (p = 0.001). After 24 and 60 months,
      the corresponding figures were 42% versus 29% (p = 0.18), and 30% versus 10% (p =
      0.02), respectively. When adjusted for sex, age and disease progression, use of
      AM was found to be an independent factor highly associated with mental distress
      at 12 months (OR = 5.5, 95% CI 2.1-14.4). Later in the study, progression/relapse
      of cancer proved to be a more important predictor of mental distress. These
      findings suggest that, in North Norway, seeking alternative treatment is more
      common among mentally distressed cancer patients.

PMID- 14651210
TI  - Patient preference for dissection of sentinel nodes outside level I-II of the
      axilla.
AB  - In this study patients' and female doctors' opinions about harvesting sentinel
      nodes outside the axilla are evaluated and patients' ability to understand the
      concept of sentinel node biopsy is investigated. Information leaflets and
      questionnaires were mailed to 100 patients with breast cancer who had undergone
      sentinel node biopsy and to 300 female doctors. Seventy-three (73%) patients and
      148 (49%) female doctors returned the questionnaire. Fifty-eight (79%) breast
      cancer patients and 71 (48%) female doctors wanted harvesting to be done in order
      to determine whether the nodes were involved. Sixty-six (90%) patients and 128
      (86%) female doctors wanted the procedure if it changed the treatment. Sixty
      (82%) patients understood the outcome of the sentinel node procedure. Patients
      with breast cancer seem to value the information gained by harvesting sentinel
      nodes outside the axilla and want the procedure if there is even the slightest
      possibility that it might change the adjuvant treatment.

PMID- 14651211
TI  - Patients above sixty years of age with Hodgkin's lymphoma treated with a new
      strategy.
AB  - In the Swedish National Care Programme for Hodgkin's lymphoma (HL) a less
      intensive chemotherapy regimen with individualized dosing (LVPP/OEPA) was
      introduced in 1989. In total, 139 patients, 77 between 1985 and 1988 and 62
      between 1989 and 1992, were studied. Mean ages were 72 and 71 years,
      respectively. One hundred and nineteen patients were treated with curative
      intention, 63 (82%) between 1985 and 1988 vs. 56 (90%) between 1989 and 1992 (p =
      0.11). All patients (13 vs. 20) treated with radiotherapy only achieved a
      complete remission (CR). The CR rates (67% vs. 65%) for patients treated with 6-8
      cycles of chemotherapy were also similar in the two time periods. The 5-year
      survival rate was 45% in the period 1985-1988 and 48% in 1989-1992. The survival
      of elderly HL patients was thus not improved from 1985-1988 to 1989-1992. Thus
      efforts to improve the chemotherapy regimen with individualized dosing did not
      change the outcome. Many patients experienced myelosuppression and opportunistic
      infections that may have contributed to the poor treatment results.

PMID- 14651212
TI  - Cytotoxic treatment of aggressive prostate tumors with or without neuroendocrine
      elements.
AB  - The aim of this study was to investigate whether there is an association between
      the presence of neuroendocrine elements in relapsed prostate cancer and
      sensitivity to estramustine/etoposide and carboplatin or cisplatin. Thirty
      patients with progressive metastatic castrate prostate cancer were selected on
      the basis of clinical criteria for treatment with cytotoxic chemotherapy. The
      criteria included a tumor biopsy specimen taken during relapse showing
      neuroendocrine features based on morphology alone (carcinoid elements, small cell
      tumor) or by immunohistochemistry (detection of chromogranin A, neuron-specific
      enolase or synaptophysin). Patients were treated with cis- or carboplatin,
      estramustine (orally) and etoposide (orally or intravenously). Remission of
      radiographically visualized lesions, decline of prostate-specific antigen (PSA)
      or death owing to any cause constituted (separately reported) the endpoints.
      Tumor remission was found in about half of the patients, determined either by
      changes in measurable lesions or by a 50% decline in serum PSA. Neuroendocrine
      elements--irrespective of how they were identified--were not predictive of tumor
      remission or survival. Regression of measurable lesions by > 50% was seen in 4/9
      (44%) cases of small cell carcinoma, 6/13 (46%) of poorly differentiated
      carcinoma, 7/13 (54%) of tumors with one marker immunohistochemically detected
      and 3/7 (43%) of tumors without any staining. It is concluded that response to
      chemotherapy was not predicted solely on the basis of the presence or absence of
      neuroendocrine elements in a relapsed tumor specimen. The results support the use
      of cytotoxic drugs in the relapsed setting and definitive trials are ongoing to
      prove any benefit to survival.

PMID- 14651213
TI  - Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk
      primary operable breast cancer--a quality assessment study.
AB  - From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support
      was used as an adjuvant treatment strategy for management of primary high-risk
      breast cancer patients with more than five positive nodes. This single
      institution study included 52 women aged < or = 56 years with primary operable
      breast cancer and > or = 6 tumour-positive axillary lymph nodes. The treatment
      regimen consisted of at least three initial courses of FEC (5-fluorouracil,
      epirubicin, cyclophosphamide) followed by high-dose chemotherapy
      (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral
      blood stem-cell reinfusion. This study focuses on quality control including
      evaluation of toxicity, supportive therapy and assessment of the stem-cell
      products. Cytokeratin 19 positive cells were found in the stem-cell product from
      3/37 patients. Data regarding organ toxicity were used for evaluation of short-
      and long-term side effects. Substantial acute toxicity and frequent catheter
      related infections were found. Long-term toxicities included reduced lung
      diffusion capacity (n = 36), fatigue (n = 14), arthralgia/myalgia (n = 10),
      neurotoxicity (n = 9) and memory loss (n = 4). However, most toxicities were
      grade 1-2 and reversible within two years. No treatment-related death occurred.
      Within a median follow-up of 30 months (range, 11-57), 25% of the patients had
      relapsed. Recurrence-free survival was 75% and overall survival was 88% three
      years after the start of treatment. Overall, high-dose chemotherapy was
      relatively well tolerated, with manageable toxicity and an acceptable requirement
      of supportive therapy. Until now, high-dose chemotherapy has not proven superior
      to conventional-dose adjuvant chemotherapy, therefore it is necessary in the
      future to focus on well-designed randomized studies.

PMID- 14651214
TI  - Maintained salivary function after brachytherapy in patients with head and neck
      carcinomas--evaluation using quantitative salivary gland scintigraphy.
AB  - The purpose of this study was to determine whether or not salivary gland
      dysfunction occurs within the first three months after brachytherapy in patients
      with head and neck carcinoma. Of the 20 patients with head and neck squamous cell
      carcinoma included in this study, 11 were treated with brachytherapy and the
      remaining 9 patients received external irradiation. All the patients underwent a
      salivary gland scintigraphy before and after radiotherapy. The scintigraphic
      parameters of each major salivary gland were then compared before and after the
      radiotherapy. In the brachytherapy group, none of the scintigraphic functional
      parameters showed a significant change before and after the radiotherapy. In
      contrast, all of the parameters with the exception of the uptake ratio (UR) of
      the submandibular glands significantly decreased after external irradiation. This
      observation was to be expected owing to the different irradiation doses
      administered by the two techniques. The scintigraphic technique used to evaluate
      salivary gland function should be used in future intensity-modulated radiation
      therapy salivary-gland-sparing studies in order to evaluate both the acute and
      chronic effects of irradiation in head and neck cancer patients.

PMID- 14651215
TI  - Phase II study of gemcitabine, UFT and leucovorin in patients with advanced
      pancreatic cancer.
AB  - The combination of gemcitabine with protracted 5-fluorouracil (5-FU) in the
      treatment of metastatic pancreatic cancer has shown activity with tolerable
      toxicity. The administration of UFT may simulate the effects of a protracted
      infusion of 5-FU. Patients with previously untreated metastatic or unresectable
      measurable pancreatic adenocarcinoma received gemcitabine (800 mg/m2 i.v.,
      administered as an 80-min infusion on days 1, 8 and 15), UFT (200 mg/m2/day, on
      days 1 to 21), and oral leucovorin (90 mg/day, on days 1 to 21). Thirty patients
      were enrolled in this study. Five patients had partial responses, with an overall
      response rate of 17% (5/30), using the intent-to-treat principle (95% confidence
      interval (CI), 3-30%). Nine out of 25 (36%) patients experienced clinical benefit
      responses (95% CI; 17-55%). The median time to progression was 3.0 months, and
      the median overall survival was 7.2 months. The principal adverse event was
      neutropenia. The combination of gemcitabine, UFT, plus oral leucovorin shows
      significant antitumor activity and a beneficial clinical effect with an
      acceptable level of toxicity.

PMID- 14651216
TI  - Chalkley estimates of angiogenesis in early breast cancer--relevance to
      prognosis.
AB  - The aim of this study was to investigate whether Chalkley estimates of
      angiogenesis add new knowledge regarding prediction of prognosis in 455
      consecutive early breast carcinomas, both node-positive (52%) and node-negative
      (48%). Median follow-up was 101 months. Intense vascularization indicated poor
      disease-specific (p = 0.003) and overall (p = 0.004) survival. In node-negative
      patients, Chalkley counts were not associated with prognosis, whereas in node
      positive patients, high Chalkley scores indicated poor disease-specific (p =
      0.0006) and overall (p = 0.0008) survival. A multivariate analysis showed that
      positive lymph nodes, high histopathological grades, and negative oestrogen
      receptors were independent markers of cancer-related death. A high
      histopathological grade was associated with cancer-related death in node-negative
      patients, whereas in node-positive patients, many lymph nodes, high malignancy
      grade, negative oestrogen receptor, and increasing Chalkley counts (both tertiles
      and continuous) were independent markers of disease-specific death. Thus, in a
      univariate analysis it was found that high Chalkley estimates of angiogenesis
      indicated a poor prognosis, but high Chalkley estimates were independent
      prognostic markers only in node-positive patients.

PMID- 14651217
TI  - Cytomegalovirus colitis--a severe complication after standard chemotherapy.
AB  - We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year
      old patient after a first course of standard chemotherapy for a small cell lung
      carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and
      IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA
      was positive. Lymphopenia and diminished CD4 T-cell counts were observed.
      Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died
      several months later of metastatic lung cancer. Significant immunosuppression
      leading to severe colitis by CMV infection or reactivation can occur after
      standard chemotherapy.

PMID- 14651218
TI  - Cell lines with potential for megakaryocytic differentiation: a review.
AB  - Megakaryocyte development is a complex cell developmental process, and
      megakaryocytic cell lines offer an alternative approach and provide a useful tool
      in order to better understand megakaryocytopoiesis. This review attempts to
      consolidate recent observations made on megakaryocytic cell lines.

PMID- 14651219
TI  - Production of cytokines by rat immunocytoma clonal variants: a new type of
      intratumor heterogeneity.
AB  - A long-term tissue culture line of highly metastatic IR202 immunocytoma of LOU
      rats, and five of its clones (B4, C2, C4, C5, D3) was examined for their ability
      to produce cytokines. A combination of cytokine detection bioassays was employed
      in order to compensate for differences in sensitivity and specificity, and the
      possibility of inhibitors masking an activity. All the IR202 variants tested were
      shown to secrete constitutively varying amount of interleukin (IL-6). In
      addition, most of the cells produce IL-10 and TGF-beta, except clones C4 and C2,
      respectively. Moreover, supernatants from clone B4, C2, C4, and D3 may contain
      low levels of soluble IL-1. Membrane-bound IL-1 was found on the surface of B4,
      C4, and D3 cells. None of the IR202 variants, however, produced IL-2, IL-4, tumor
      necrosis factor-alpha (TNF-alpha), or LT. These results are consistent with the
      concept of a new type of intratumor heterogeneity and the ability of immunocytoma
      tumors to generate different immunoregulatory molecules in tumor-bearing hosts.

PMID- 14651220
TI  - Successful pregnancy in a young woman with essential thrombocythemia treated with
      platelet apheresis.
AB  - We report a 27-year-old woman with essential thrombocythemia who had delivered a
      healthy baby after Caesarian section. The patient was treated with two courses of
      platelet apheresis at the beginning of the gestation. Subsequent to this
      procedure, the platelet count decreased progressively and remained at about
      500,000/microl of blood until delivery without any further treatment. Caesarian
      section was performed at the 37th week when the placenta presented grade III
      lesions on ultrasound examination. Histology of the placenta revealed multiple
      infarcts. Platelet count in the newborn was normal. We concluded that essential
      thrombocythemia is not a risk factor for pregnancy, and that platelet count may
      decrease during pregnancy. In addition, an emergent reduction of platelets may
      easily be obtained by platelet apheresis.

PMID- 14651221
TI  - Myopathy with tubular aggregates and hypertrophic cardiomyopathy in a patient
      with type IIA von Willebrand disease.

PMID- 14651222
TI  - Cytologically distinct acute leukemia in sibs exposed to the same leukemogen.

PMID- 14651223
TI  - Evaluation of the Pall RC100 leucocyte removal filters and the effect of air
      introduction on its performance.
AB  - We evaluated the efficiency of Pall RC100 leucocyte removal filters in processing
      two units of concentrated red cells for transfusion. Our results show that the
      filter is very effective in processing the first unit. However, 32% (5/16) of the
      filters evaluated allowed a leak of substantial numbers of white cells towards
      the end of the transfusion of the second unit of blood. Air introduction
      experiments showed that as little as 2 ml of air in the filter may cause major
      deterioration of the filter function.

PMID- 14651224
TI  - Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of
      cancer, and use in other diseases.
AB  - Pentostatin (2'-deoxycoformycin, dCF) is a purine nucleoside analog and a product
      of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor
      of adenosine deaminase (ADA), an enzyme essential in the cellular metabolism of
      purines. Children with congenital absence of ADA suffer from atrophy of lymphoid
      tissues and severe combined immune deficiency (SCID) syndrome. It was
      hypothesized that pentostatin would be lymphocytotoxic and this proved to be
      true; this finding prompted its investigation in lymphoid neoplasms. It was
      anticipated that pentostatin would be most active in neoplasms with high
      intracellular concentrations of ADA, e.g. acute lymphocytic leukemia (ALL),
      particularly of the T-cell variety. Although pentostatin proved to be active in
      ALL, large doses were required and major toxic effects outweighed therapeutic
      benefits. By contrast, pentostatin proved to be exceptionally active in hairy
      cell leukemia (HCL), a B-cell neoplasm with low intracellular concentrations of
      ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic
      leukemia, prolymphocytic leukemia, cutaneous T-cell lymphomas, adult T-cell
      lymphoma-leukemia, and low grade non-Hodgkin's lymphomas. It potentiates the
      activity of vidarabine against viruses and against the cells of acute myeloid
      leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not
      been adequately evaluated in other solid tumors. The toxic effects of pentostatin
      include renal failure, central nervous system (CNS) depression, immunosuppresion,
      keratoconjunctivitis, and opportunistic infections. In the absence of pre
      existing bone marrow compromise, pentostatin produces only mild myelosuppression.
      Aside from its use as an antineoplastic agent, pentostatin has potential
      applications as an immunosuppressive drug, as an antiviral agent, as an
      antimalarial compound, and in the protection of cells of the CNS from damage
      induced by ischemia and anoxia. Clinical studies with pentostatin are ongoing,
      and its roles in the management of neoplastic and non-neoplastic diseases have
      yet to be fully defined.

PMID- 14651225
TI  - Tumor necrosis factor in advanced gastrointestinal neoplasms. A clinical trial
      with a focus on haematological effects.
AB  - This paper presents the results of the clinical trial with the use of hr TNF
      alpha (human recombinant tumor necrosis factor-alpha) in 16 advanced
      gastrointestinal cancer patients. Hr TNF-alpha was administered intravenously in
      a short, 30-min infusion. According to authors' previous experiences with daily
      dose escalation (modified Fibonacci scheme), a daily dose of 150 microg/m2 was
      established as safe, and was well tolerated by the patients. The treatment
      consisted of 5-day cycles, repeated six times, every 14 days. Special attention
      was paid regarding the possible side-effect and safety of hr TNF-alpha
      administration in men, as many acute and chronic haematological toxicities have
      been reported. After careful analysis of TNF-alpha side-effects, we did not find
      any acute haematological complications (e.g. thrombosis, DIC, embolism) in any of
      the patients. Haemoglobin values and erythrocyte and leucocyte counts gradually
      decreased during each cycle, with the tendency for spontaneous renewal after the
      treatment had been completed. No cases of thrombocytopenia and severe neuropenia
      were observed.

PMID- 14651226
TI  - Mitoxantrone and cytosine arabinoside in previously untreated adult patients with
      acute non-lymphocytic leukemia.
AB  - Twenty-five adult patients with previously untreated acute non-lymphocytic
      leukemia (ANLL) were treated with mitoxantrone (Mto) 12 mg/m2 daily by 30 minutes
      intravenous (IV) infusion for 3 days and cytosine arabinoside (Ara-C) 200 mg/m2
      daily by continuous infusion for 7 days, as an induction therapy. After complete
      remission (CR) was observed, they were given two more courses of consolidation
      therapy which was as Mto 12 mg/m2 daily by 30 minutes IV infusion for one day,
      and Ara-C 200 mg/m2 daily by 30 minutes IV infusion for 5 days. CR was obtained
      in 18 of 25 patients (72%). Median remission duration was 294 days and length of
      survival was 366 days. 11 patients (44%) are still in remission. Myelosupression
      developed in all patients following induction therapy, but it was not observed
      after consolidation therapies. Non-hematological side-effects consisted of
      nausea, vomiting, alopecia, stomatitis, and transient elevation in liver enzymes.
      Our therapeutic responses are similar to those obtained by others.

PMID- 14651227
TI  - Bilateral primary malignant lymphoma of the breast during pregnancy.
AB  - The authors report a case of bilateral primary malignant lymphoma of the breast
      presenting during pregnancy in a 24-year-old woman. After the delivery of a
      healthy premature infant by Caesarean section, polychemotherapy was employed. The
      efficacy of the treatment could not be evaluated since the patient died within a
      very short period of time. Autopsy and histological examination revealed
      infiltration of Burkitt-type lymphoma in the breast, ovary, brain, liver, kidney,
      adrenal gland, pancreas, stomach, bone marrow and myocardium.

PMID- 14651228
TI  - Continuing professional development with distance learning.

PMID- 14651229
TI  - Patient satisfaction with mandibular implant overdentures and conventional
      dentures 6 months after delivery.
AB  - PURPOSE: This study examined patient satisfaction with conventional complete
      dentures and mandibular implant overdentures opposing conventional maxillary
      dentures 6 months after delivery. MATERIALS AND METHODS: Sixty edentulous
      subjects (aged 65 to 75 years) were randomly assigned to either a mandibular
      conventional denture or an overdenture supported by two implants with ball-shaped
      retentive anchors. Patients rated their general satisfaction and other features
      of their prostheses, together with their ability to eat certain food items, on
      100-mm visual analogue scales before assignment, and after 2 and 6 months.
      RESULTS: Both treatment groups reported greater satisfaction with their new
      prostheses at 6 months. General satisfaction ratings were higher in the implant
      group than in the conventional denture group by approximately 36% (mean
      difference 22.3 mm). The implant group also rated comfort (mean difference 22.4
      mm), stability (mean difference 28.5 mm), and ability to chew (mean difference
      17.3 mm) significantly higher. Significantly higher scores were also given by the
      implant group for their ability to chew certain hard foods. A trend for an
      increase in the differences between the groups, in favor of the implant group,
      was observed between the 2- and 6-month recalls, although the increase was only
      significant for ease of cleaning. The primary influence on general satisfaction 6
      months after the delivery of the prostheses was the provision of the two-implant
      overdenture. CONCLUSION: Edentulous seniors who received mandibular implant
      overdentures opposing a conventional denture rated their general satisfaction
      approximately 36% higher than did a comparable group provided with new
      conventional dentures.

PMID- 14651231
TI  - In vivo forces on implants influenced by occlusal scheme and food consistency.
AB  - PURPOSE: The aim of this study was to investigate whether systematic
      modifications of occlusal features or food consistency are suitable to reduce the
      loading of implants. MATERIALS AND METHODS: Ten healthy subjects, each of whom
      had a gap in the chewing center (second premolar or first molar) of one lateral
      dental arch, were provided with fixed partial dentures (FPD) on two ITI implants.
      Strain gauges attached to the abutments recorded forces in three dimensions. In
      each person, the original FPD was successively replaced by three FPDs with
      different occlusal schemes: The first had steep cusps, the second had flat cusps,
      and the third had the same cuspal inclination as the first but a narrow occlusal
      surface. Subjects chewed gummy bears and bread as a tough and a soft bolus,
      respectively. RESULTS: In chewing of gummy bears, the mean vertical forces of the
      three FPDs ranged between 264 and 284 N and were not significantly different. The
      mean bending moments amounted to 27 Ncm and 24 Ncm with steep and flat occlusal
      slopes, respectively. With the narrow occlusal surface, the bending moments were
      reduced by 48%, to a mean of 11 Ncm. Chewing of bread yielded similar relations
      with lower mean vertical forces and bending moments. CONCLUSION: Narrowing the
      orovestibular width of the occlusal surface by 30% caused a significant reduction
      of lateral force components. A reduced orovestibular width of the occlusal
      surface is recommended in unfavorable loading conditions. In addition, the
      chewing of soft food is suggested during the healing period in cases of immediate
      loading.

PMID- 14651230
TI  - Influence of core thickness on a restored crown of a first premolar using finite
      element analysis.
AB  - PURPOSE: This study examined the influence of ceramic coping thickness on the
      maximum stresses that arise in a first premolar all-ceramic crown. MATERIALS AND
      METHODS: Axisymmetric finite element models with different In-Ceram Alumina
      coping thicknesses (0.3, 0.6, and 0.9 mm) were examined. Models with and without
      resin lute were constructed. To all models, an identical axial load of 600 N was
      applied vertically downward, over an area around the crown's fissure. RESULTS:
      The resulting peak tensile maximum principal stresses in each part of the crown
      existed below the fracture strengths of the respective materials making up the
      crown. This was true for all variations of core thickness, with and without resin
      lute. The peak tensile stresses in the coping, porcelain, and dentin decreased
      for an increase in core thickness. This was most evident in the porcelain and
      coping. CONCLUSION: The thickness of the ceramic core has a significant influence
      on the resulting stresses in the coping, porcelain, and dentin of this axially
      loaded crown.

PMID- 14651232
TI  - Probability of failure of veneered glass fiber-reinforced composites and glass
      infiltrated alumina with or without zirconia reinforcement.
AB  - PURPOSE: The probability of failure under flexural load of veneered specimens of
      a unidirectional glass fiber-reinforced composite (FibreKor/Sculpture), a
      bidirectional glass fiber-reinforced composite (Vectris/Targis), a glass
      infiltrated alumina (In-Ceram Alumina/Vita alpha), and a zirconia-reinforced
      glass-infiltrated alumina (In-Ceram Zirconia/Vita alpha) was investigated; a
      metal-ceramic (PG200/Vita omega) system served as a control. MATERIALS AND
      METHODS: Ten uniform beams of the veneered core materials were fabricated for
      each system and subjected to a three-point bending test. The data were analyzed
      using the Weibull method. The failure load of specimens at a 10% probability of
      failure (B10 load) was compared. The mode of failure was analyzed. RESULTS: The
      B10 load of the systems investigated was not significantly different from that of
      the metal-ceramic system. FibreKor possessed significantly higher B10 load than
      Vectris, In-Ceram Alumina, and In-Ceram Zirconia. The B10 strength loads of
      Vectris, In-Ceram Alumina, and In-Ceram Zirconia were not significantly different
      from one another. CONCLUSION: The probability of FibreKor to fracture under a
      flexural load was significantly lower than that of Vectris, In-Ceram Alumina, or
      In-Ceram Zirconia.

PMID- 14651233
TI  - Effect of Nd:YAG laser irradiation on shear bond strength of glass-lonomer luting
      cement to dentin surface.
AB  - PURPOSE: The purposes of this study were to evaluate the shear bond strength of
      luting glass-ionomer cement to a dentin surface treated by pulsed Nd:YAG laser
      irradiation, and to prove the hypothesis that the bond strength of glass-ionomer
      luting cement to dentin is favorably altered after Nd:YAG laser irradiation.
      MATERIALS AND METHODS: Sixty-four extracted human molars with an exposed flat
      dentin surface were divided into four groups (n = 16). After painting black ink
      on their surfaces, the teeth of groups 1, 2, and 3 were irradiated by an Nd:YAG
      laser at 1.064-microm wavelength at 1, 2, and 3 W, respectively; group 4 was
      untreated and served as a control. Some specimens of each group were used for
      morphologic and atomic analytic study, and the others were used for shear bond
      testing. The shear bond test was performed after cylindric titanium specimens
      were cemented with glass-ionomer cement on a circular dentin area and specimens
      were immersed in distilled water. The tested specimens were also morphologically
      investigated. RESULTS: Shear bond strength of group 3 was significantly higher
      than that of the control group. Morphologic observation of the cement-dentin
      interface showed good adaptation of the luting cement to laser-treated dentin.
      Analysis of atomic contents on the dentin surface showed a significant increase
      of calcium:phosphorus ratio after laser irradiation. CONCLUSION: The dentin
      surface was modified morphologically and chemically, and the shear bond strength
      of glass-ionomer luting cement to dentin was increased by Nd:YAG laser
      irradiation at 3 W.

PMID- 14651234
TI  - Shear bond strength between composite resin and denture teeth: effect of tooth
      type and surface treatments.
AB  - PURPOSE: The purpose of this study was to investigate the strength of the
      composite resin-denture tooth bond as affected by different tooth surface
      treatments. MATERIALS AND METHODS: Spectrum TPH was condensed on 112 mandibular
      first molar acrylic resin and composite resin denture teeth, which received seven
      different treatments: Four groups were treated with Prime & Bond NT adhesive, and
      three groups were treated with One Step adhesive. Four groups (two of each
      adhesive category) were treated with Composite Activator and air abrasion. In one
      group, AeliteFlo was used just before the condensation of Spectrum TPH. Bond
      strength was evaluated with a shear test device on a Monsanto testing machine.
      The results were evaluated statistically with two-way ANOVA and the Scheffe
      method. RESULTS: There was a significant interaction between denture tooth type
      and surface treatments. Bond strength of composite resin was greater to composite
      than to acrylic resin teeth when the bond was mediated only with adhesives. One
      Step adhesive and AeliteFlo resulted in a higher bond of composite resin to both
      types of teeth. Wetting tooth surfaces with Composite Activator did not increase
      the bond. CONCLUSION: When repairing denture teeth with composite resin and
      adhesives, the bond strength was higher with composite than with acrylic resin
      teeth, and there were differences between the adhesives used.

PMID- 14651235
TI  - Effect of nucleation temperature on fracture toughness (KIC) of fluorcanasite
      based glass-ceramic.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that nucleation
      temperature significantly affects the fracture toughness of a fluorcanasite-based
      glass-ceramic. MATERIALS AND METHODS: Sixty specimens were cut from a glass bar,
      polished, and randomly divided into six groups for nucleation treatment at
      temperatures of (1) 520 degrees C, (2) 550 degrees C, (3) 580 degrees C, (4) 610
      degrees C, (5) 640 degrees C, and (6) 670 degrees C for 4 hours and a
      crystallization temperature of 850 degrees C for 6 hours. A precrack was produced
      at the center of each bar, and the prepared specimens were subjected to three
      point flexural loading with the cracked surface under tension using an Instron
      machine at a cross-head speed of 0.5 mm/min. Fracture toughness was calculated
      based on the indentation strength technique, and crystal volume fraction was
      determined by quantitative stereology of SEM images of each group of ceramic
      specimens. RESULTS: The mean fracture toughness and crystal volume fraction
      ranged from 2.6 to 3.5 MPa x m1/2 and from 65% to 81%, respectively, within the
      limits of the nucleation temperatures investigated. ANOVA showed statistically
      significant differences among the test groups. Based on Duncan's multiple
      comparison test, significant differences in mean fracture toughness and crystal
      volume fraction were found among the following statistical subsets: groups 1 to
      4, group 5, and group 6. CONCLUSION: Fracture toughness and crystal volume
      fraction of a fluorcanasite-based glass-ceramic were strongly influenced by
      nucleation temperature; the crystals precipitated during thermal processing are
      thought to be an important factor in increasing fracture toughness.

PMID- 14651236
TI  - A retrospective study of Mirage ceramic inlays over up to 9 years.
AB  - PURPOSE: The aim of this retrospective longitudinal study was to document the
      outcomes of resin-cemented ceramic inlays in patients treated in a private dental
      practice over up to 9 years. MATERIALS AND METHODS: Fifty-two patients received
      in all 109 Mirage ceramic inlays, 59 in molars and 50 in premolars. Follow-up
      data were collected on 51 patients and 107 inlays. The mean time in situ was 6.3
      years. Technical failures or dislodgments of the inlays were recorded, as well as
      clinical and radiographic signs of periodontal and periapical diseases or caries
      lesions. RESULTS: During the follow-up period, 17 inlays had to be removed, 14
      because of major fractures and 3 in teeth requiring endodontic treatment. The
      fractures were confined to 8 of the 51 patients available for follow-up and were
      significantly more common in molars than in premolars. Replacement of inlays was
      significantly more frequent in men than in women. During the study period, 20
      further minor clinical interventions (eg, recementation of intact inlays, repair
      of minor fractures or caries defects) had been undertaken on the surviving
      inlays. Thus, major and minor complications together necessitated a total of 37
      clinical interventions. The survival rate, based on the remaining 90 inlays still
      in situ, was 84%. CONCLUSION: In this material, the outcome of ceramic inlay
      therapy was influenced by both major and minor complications (35%). Eight of the
      51 patients accounted for all the major fractures, implying that patient
      selection is an important determinant of the clinical outcome.

PMID- 14651237
TI  - Sentiments expressed in relation to tooth loss: a qualitative study among
      edentulous Saudis.
AB  - PURPOSE: The objective was to explore and gain insight into the sentiments
      surrounding tooth loss in a group of edentulous Saudis. MATERIALS AND METHODS:
      Using a qualitative methodology, 44 edentulous patients who were receiving
      complete denture treatment were interviewed in private, in the Arabic language.
      Interviews were tape recorded and semistructured, following a list of
      predetermined and piloted topics, but dialogue also took place, with the freedom
      for both interviewer and interviewee to explore areas of interest. All recordings
      were transcribed, translated into English, and interpreted independently by two
      members of the team to identify the core themes associated with tooth loss.
      RESULTS: The mean age of participants was 58.9 years (range 35 to 72 years), and
      they had been edentulous for a mean of 7.1 years (range 3 months to 22 years).
      The main themes related to tooth loss were unqualified acceptance, inevitability
      with old age, behavior changes with respect to eating comfort, aged appearance,
      self-responsibility, positively perceived benefits, high prosthetic expectations
      and reduced level of denture satisfaction, and some need for privacy. CONCLUSION:
      The lack of any outward indication that participants experienced bereavement
      suggests that outlook on life can influence the impact of tooth loss.
      Participants' unqualified acceptance of their edentulous fate, yet their clear
      need to "normalize" oral function, reflects a degree of pragmatism toward life
      events. The strong influence of religion in Saudi society is a possible factor in
      the sentiments expressed.

PMID- 14651238
TI  - Maintenance requirements of implant-supported fixed prostheses opposed by implant
      supported fixed prostheses, natural teeth, or complete dentures: a 5-year
      retrospective study.
AB  - PURPOSE: The purpose of this study was to compare the maintenance requirements of
      implant-supported fixed prostheses with cantilever arms in edentulous jaws when
      opposed by fixed prostheses of similar design, by natural teeth, or by complete
      dentures. MATERIALS AND METHODS: The maintenance requirements for the 5-year
      follow-up period were obtained by examining the dental records of 37 people. Six
      were provided with fixed prostheses in both arches, 22 with a fixed prosthesis in
      the mandible opposed by a complete denture, and 9 with a fixed prosthesis opposed
      by natural teeth. Everyone was treated with Nobel Biocare implants using standard
      implant and prosthetic protocols. RESULTS: The denture teeth and acrylic resin
      were repaired on 44 occasions in the group with implants in both jaws, on 14
      occasions in the group with implants opposed by natural teeth, and twice in the
      group in which the implants were opposed by a complete denture. The group with
      implants in both jaws was more likely to fracture the gold-alloy framework, which
      occurred on six occasions. The group with implants in both jaws was significantly
      different from the other two groups in relation to higher incidence of fracture
      of the teeth and gold-alloy framework. CONCLUSION: The maintenance requirements
      of implant-supported fixed prostheses with cantilever arms opposed by fixed
      prostheses of similar design were much greater than when opposed by natural teeth
      or complete dentures.

PMID- 14651239
TI  - Status of teeth adjacent to single-tooth implants.
AB  - PURPOSE: This study evaluated the status of teeth adjacent to single-tooth
      implants in the anterior and posterior jaw during a follow-up of more than 3
      years. MATERIALS AND METHODS: Seventy-eight single-tooth implants and 148
      adjacent teeth were followed for a mean of 58 months. Implant survival rate, peri
      implant structures, and prosthetic complication rates were evaluated. Crowns and
      periodontal status of adjacent teeth were compared at crown placement and at the
      last examination. Horizontal distance from the implant edge to adjacent teeth was
      calculated and compared for anterior and posterior regions. The influence of
      approximal crestal bone resorption of the adjacent teeth was calculated using
      multivariate regression analysis. RESULTS: The clinical findings for implants
      (one loss), peri-implant structures, and prosthetic complication rates (three
      crown fractures) were excellent. There was a high proportion of intact adjacent
      teeth in both anterior and posterior regions at crown placement and at the follow
      up examination. No adjacent teeth required extraction or endodontic treatment,
      and only four required restoration. Comparison of the periodontal status at crown
      placement and at follow-up revealed no differences for plaque and bleeding
      indices or for pocket depth of adjacent teeth. There was a significant influence
      of the horizontal distance on approximal bone loss in the closer distance of the
      anterior region, but not in the posterior region. CONCLUSION: The crown and
      periodontal status of teeth adjacent to single-implant restorations was
      excellent. The approximal bone crest reduction of the adjacent teeth was
      significantly influenced by the horizontal distance between the implant edge and
      neighboring tooth.

PMID- 14651240
TI  - Peri-implant mucosal level in patients treated with implant-supported fixed
      prostheses: a 1-year follow-up study.
AB  - PURPOSE: The purpose of this follow-up study was to quantify the change in the
      peri-implant mucosal level after treatment of edentulous patients with fixed
      prostheses on osseointegrated endosseous implants. MATERIALS AND METHODS: Twenty
      patients were included in the study: 10 were treated in the maxilla, and 10 were
      treated in the mandible. Both groups had fixed prostheses on osseointegrated
      Branemark implants. Peri-implant mucosal level was measured with a calibrated
      probe after removal of the prostheses at the 1-year follow-up. These measurements
      were compared to those made on the original master casts. RESULTS: A larger mean
      retraction (-) was observed in the mandible (-1.6 mm) compared to the maxilla (
      0.8 mm), but there was great variation. The individual values varied from -4.5 to
      +1.0 mm in the mandible and from -6.0 to +6.0 mm in the maxilla. CONCLUSION: Peri
      implant soft tissue recession occurs during the first year in edentulous jaws
      after treatment with implant-supported fixed prostheses and more so in the
      maxilla than the mandible.

PMID- 14651241
TI  - Effect of new dentures on interocclusal distance during speech.
AB  - PURPOSE: The aim of this study was to investigate the changes in interocclusal
      distance during the pronunciation of /m/ and /s/ sounds in the Portuguese
      language, in partially edentulous patients before and after insertion of new
      dentures. MATERIALS AND METHODS: Subjects were divided into a control group
      consisting of 18 completely dentate patients and an experimental group consisting
      of 18 patients who were edentulous in the maxilla and classified as Kennedy Class
      I in the mandible. The experimental group had new dentures placed and the
      occlusal vertical dimension corrected. A magnetic jaw-tracking device measured
      the interocclusal distance during pronunciation of the /m/ and /s/ phonemes.
      Interocclusal distance evaluations were carried out in a single session for the
      control group. In the experimental group, the measurements were carried out
      before insertion of new dentures; immediately after insertion; and after 6 and 24
      hours; 2 days; 1 and 2 weeks; 1, 2, 3, and 6 months; and 1 year. RESULTS:
      Comparison between groups revealed significant difference in interocclusal
      distance for the /m/ sound both before and after insertion of dentures up to 2
      months. For the /s/ phoneme, there was no difference between the groups before
      prosthesis insertion, or after 3, 6, and 12 months of prosthesis use. There were
      significant differences for the /m/ sound only at 6 and 12 months after new
      denture insertion, and for the /s/ sound at all periods evaluated. CONCLUSION:
      Insertion of new dentures, with the vertical dimension corrected, changes the
      interocclusal distance of speech during phonation of /m/ and /s/ sounds.

PMID- 14651243
TI  - Integration of laser surface digitizing with CAD/CAM techniques for developing
      facial prostheses. Part 2: Development of molding techniques for casting
      prosthetic parts.
AB  - PURPOSE: This article presents a novel manufacturing approach that integrates
      laser surface digitizing/scanning and computer-aided design and manufacturing
      (CAD/CAM) to achieve automated fabrication of spatially and anatomically accurate
      extraoral facial prostheses. MATERIALS AND METHODS: Contrary to the approach in
      part 1 for fabricating positive replicas of prostheses, the approaches presented
      here are focused on designing and producing negative molds of the final
      prostheses using CAD, rapid prototyping, and rapid tooling techniques. The molds
      were applied directly to cast the final prostheses, thereby eliminating
      conventional flasking and investing procedures. RESULTS: Three different facial
      prostheses were produced to evaluate the proposed approach for prosthesis
      production. The advantages of this alternative manufacturing approach over the
      approach presented in part 1 and conventional techniques are discussed. The
      limitations encountered with the integrated manufacturing system are highlighted.
      CONCLUSION: With the new techniques, reduced patient discomfort, minimal
      dependence on the artistic skills of the prosthetist, and short turnaround times
      for prosthesis production can be expected.

PMID- 14651242
TI  - The influence of different cements on the fracture resistance and marginal
      adaptation of all-ceramic and fiber-reinforced crowns.
AB  - PURPOSE: This in vitro study investigated the marginal adaptation and fracture
      resistance of heat-pressed glass-ceramic and fiber-reinforced composite molar
      crowns luted with resin, resin-modified glass-ionomer, or zinc-oxide-eugenol-free
      cements. MATERIALS AND METHODS: A total of 24 heat-pressed all-ceramic and 24
      glass fiber-reinforced composite crowns were constructed and cemented using the
      above-mentioned luting agents (eight crowns per cement). The restorations were
      thermocycled and mechanically stressed, and fracture resistance was determined.
      Marginal adaptation was evaluated before and after stress application using
      semiquantitative analysis in a scanning electron microscope. RESULTS: All-ceramic
      and fiber-reinforced composite crowns reached the highest fracture resistance
      after stress application in combination with the resin cement. When luted with
      resin-modified glass-ionomer or zinc-oxide-eugenol-free cements, the fracture
      resistance of all-ceramics decreased significantly, while the fiber-reinforced
      composite crowns maintained their fracture resistance level; the lowest values
      were found for zinc-oxide-eugenol-free cements. The marginal adaptation remained
      unchanged after stress for all-ceramics and fiber-reinforced composite
      restorations if they were luted with resin cements. Luting with resin-modified
      glass-ionomers significantly deteriorated the marginal adaptation after stress
      application, with the exception of the crown-cement interface of all-ceramics.
      CONCLUSION: The highest fracture resistance and marginal adaptation were found
      for all-ceramic and glass fiber-reinforced composite molar crowns if they were
      luted with resin cement.

PMID- 14651244
TI  - Strength and elastic modulus of fiber-reinforced composites used for fabricating
      FPDs.
AB  - PURPOSE: The purpose of this study was to examine the flexural strength and
      elastic modulus of a new fiber-reinforced composite used for the fabrication of
      inlay-retained fixed partial dentures (FPD). MATERIALS AND METHODS: A total of
      six materials were used: Vectris, FibreKor, and an experimental material, BR-100,
      were the types of glass fiber preimpregnated with resin used for making the
      frameworks; Targis, Sculpture, and Estenia were used as the veneering composites.
      Five specimens of each material were prepared. Flexural strength and elastic
      modulus were determined using the three-point bending test. In addition, laminate
      specimens were fabricated by combination of the veneering composite and framework
      materials (Targis/Vectris, Sculpture/FibreKor, and Estenia/BR-100), and fracture
      loads of these specimens were determined. Laminate specimens were fabricated with
      three different framework thicknesses for Estenia/BR-100. RESULTS: Estenia had
      the greatest strength and highest modulus of elasticity of the veneering
      composites. All three framework materials had flexural strength values (567 to
      686 MPa) more than three times as great as those of the veneering composites (132
      to 193 MPa). Of the laminate specimens, the Estenia/BR-100 with a framework
      thickness of 1.0 mm had a fracture load more than 50% greater than Targis/Vectris
      and Sculpture/FibreKor. CONCLUSION: The combination of the experimental framework
      material BR-100 and the composite Estenia showed higher fracture loads than the
      other combinations tested.

PMID- 14651245
TI  - A prospective 5-year multicenter study of the Cresco implantology concept.
AB  - PURPOSE: The purpose of this study was to investigate the clinical and
      radiographic outcome of a prospective 5-year longitudinal multicenter test of a
      simplified implantology concept comprising an abutment-free implant system
      (Cresco) and a new method for fabrication of passively fitting superstructures,
      the Cresco Ti Precision method. MATERIALS AND METHODS: The tests were carried out
      at three different centers. Sixty partially or completely edentulous patients
      were restored by fixed implant-supported superstructures fabricated according to
      the Cresco Ti Precision method. In all, 215 Cresco implants were placed for the
      support of the superstructures. For various reasons, eight patients (13%) could
      not be followed through the 5 years. The radiographic measurements were recorded
      from radiographs exposed perpendicular to the implants. RESULTS: The initial
      implant failure rate (during the healing phase) was 2%, and the survival rate
      after loading was 98%. The mean peri-implant bone loss was 0.29 mm (SD 0.57). Of
      the measured sites, 71% showed a crestal bone loss of less than 0.5 mm. Very few
      mechanical complications were observed. This was attributed to the passively
      fitting superstructures. CONCLUSION: The results from the present multicenter
      test demonstrated that the abutment-free Cresco implantology concept is a
      reliable alternative method for implant-supported fixed prosthetic rehabilitation
      of edentulous and partially edentulous jaws.

PMID- 14651246
TI  - Simple system to record jaw movements by a home digital camcorder.
AB  - PURPOSE: Systems of recording jaw movements that are used in prosthodontics and
      orthodontics are too expensive and complicated for daily clinical diagnosis. This
      pilot study presents the development of a simple system using a camcorder and
      motion-capturing software. MATERIALS AND METHODS: Markers to detect jaw movement
      were attached to the mandibular incisors of a subject. A mirror was assembled
      beside the subject's face to detect anteroposterior movement. Jaw movements were
      recorded by a home digital camcorder. Movements of the markers were analyzed by
      motion-capturing software and transferred to 3-D data. The results were compared
      with those of a conventional system. To examine the accuracy of the measurements,
      the markers were placed on a computer-controlled x-y working stage and displaced.
      The positions of the markers were measured and analyzed, then compared with the
      true values indicated by the x-y working stage. RESULTS: The trajectories of the
      mandibular incisors recorded by the new system were very similar to those of the
      conventional system. On measurement accuracy, the mean differences between the
      measured and true values of the vertical and transverse movements were 0.07 mm
      (SD 0.03) and 0.06 mm (SD 0.04), respectively. On anteroposterior movement, the
      difference was 0.11 mm (SD 0.05). CONCLUSION: This new system can be useful for
      simple recording of jaw movements with satisfactory accuracy.

PMID- 14651247
TI  - Long-handled sponges: to bend or not to bend.
AB  - The purpose of this study was to compare upper extremity range of motion when
      using a straight-handled long-handled sponge versus a bent-handled long-handled
      sponge. Thirty-eight participants ranging in age from 20 to 55 years were
      randomly assigned to one of two order groups: straight-bent or bent-straight. The
      task involved touching a buzzer placed over thoracic vertebrae 6 and 7 with the
      long-handled sponge. The dependent variable was right upper extremity range of
      motion. Significant range of motion differences were found in wrist flexion
      extension, elbow flexion-extension, and shoulder abduction-adduction between the
      straight-handled and the bent-handled long-handled sponge (p < .05). No
      significant differences were found with ulnar and radial deviation of the wrist,
      wrist supination-pronation, or shoulder flexion (p > .05). These results suggest
      that within a normal population, the bent handle may be more beneficial to
      individuals who have decreased range of motion in shoulder abduction-adduction
      and wrist flexion-extension, whereas the straight handle may be more
      accommodating to those with decreased range of motion in the elbow. Implications
      for therapeutic evaluation include ensuring proper evaluation of range of motion
      of all upper extremity joints in order to provide assistive devices that serve
      individual needs. Future research should include special populations with upper
      extremity orthopedic conditions as well as different degrees of handle bending
      with the long-handled sponge.

PMID- 14651248
TI  - Examination of new environmental control applications.
AB  - The aim of this study was to examine the application of new Environmental Control
      Systems (ECSs) in the homes of users and caregivers. The research questions were:
      (1) Can new ECS applications improve the activities of daily living (ADL) of
      people with significant functional limitations who require personal assistance?
      (2) Can new ECS applications replace home services and lessen caregiver burden?
      To answer these questions, user satisfaction regarding ECS applications, impact
      on ADL, technical performance, and caregiver burden were examined. This
      collaborative investigation involving a local community health care center, a
      telephone monitoring service, an industrial partner, and a university research
      team used a case study approach. Five users with moderate cognitive problems or
      significant functional limitations who required personal assistance were chosen,
      along with their caregivers, for a 3-month in-home trial to test new ECS
      alternatives. The ECS in the study featured remote control functions (e.g., door
      lock release, outside intercom), specific verbal reminders (e.g., reminders to
      turn off stove elements), and automatic functions (e.g., night-lights in the
      bathroom and hallway). Information was collected in the users' homes with three
      standardized questionnaires and a company-designed questionnaire. The overall
      technical performance of the ECS was found to be in most cases moderately
      efficient. Participant satisfaction revealed that ECS alternatives needed
      improvement with respect to the service aspects such as follow-up services and
      repair/servicing. Caregiver burden was lessened for psychological aspects but not
      for physical tasks. Users seemed to have a positive perception of the impact of
      the ECS on many of their ADL. We learned six lessons from this 15-month case
      study, namely: (1) the use of remote control by people with moderate cognitive
      impairments was difficult; (2) verbal reminders were greatly appreciated; (3) the
      automatic ECS applications needed more adjustment; (4) reactions varied depending
      on the participant's perspective; (5) other assessment tools might have been
      better suited to mild cognitive problems; and (6) removal of a beneficial product
      at the conclusion of the evaluation phase raised ethical considerations.

PMID- 14651249
TI  - Ambulation aid use during the rehabilitation of people with lower limb
      amputations.
AB  - Our objective was to describe the progression of ambulation aid use by people
      with lower limb amputations during their initial rehabilitation. We prospectively
      studied 37 people with recent lower limb amputations and a mean (SD) age of 68
      (13) years. Subjects were evaluated each weekday during gait-training
      physiotherapy sessions, and the type and order of ambulation aids used during
      ambulation training were documented. The total number of gait-training sessions
      that we observed was 605, with a mean (SD) of 16.4 (7.7) sessions per participant
      and a range of 5-47. Of the 37 participants, 33 (89%) were discharged with
      prostheses. The mean (SD) number of aids per person was 2.9 (1.0). The percentage
      of participants who used each aid (presented in the mean order in which they were
      first used) were 76% parallel bars, 60% four-footed walkers, 81% two-wheeled
      walkers, 11% two crutches, 8% four-wheeled walkers, 46% two canes, and 14% one
      cane. People with lower limb amputations generally use a number of ambulation
      aids in a fairly consistent order as they progress through their initial
      rehabilitation. These findings have implications for the process of providing
      ambulation aids and provide a foundation for further study.

PMID- 14651250
TI  - Critical review of the research literature of seating interventions: a focus on
      adults with mobility impairments.
AB  - An expanding area in rehabilitation practice is the prescription of seating
      interventions for clients with mobility impairments. The goal of this
      intervention is to enhance comfort and functional performance. The purpose of
      this paper is to review the body of knowledge from the research literature
      concerning the effectiveness or impact of seating interventions for adults who
      have mobility impairments. In this review both the scope and the gaps in the
      literature are defined to identify areas for future research. Specifically, this
      review was undertaken to identify what outcomes have been examined and what
      methods have been used in carrying out the research studies. A content analysis
      based on the conceptual framework of the modified International Classification of
      Impairment, Disability, and Handicap (ICIDH) and review guidelines for evaluating
      the quality of research studies has been helpful in informing future research
      design in this area. The results of the 16 studies that comprised this review
      indicate that the majority of research conducted thus far has numerous
      methodological limitations, which in turn limits the extent to which this body of
      research can be drawn upon to provide evidence for effectiveness in seating
      interventions. There was an emphasis on constructs at the impairment level and
      inadequate attention to functional and psychosocial issues. Recommendations
      regarding future research required to support this specific type of intervention
      are presented. This research review is an important first step in facilitating
      discussion among researchers, clinicians, research funders, and seating device
      users regarding future priorities for research and development in this practice
      area.

PMID- 14651251
TI  - Dissatisfaction and nonuse of assistive devices among frail elders.
AB  - This article is based on the Rehabilitation Engineering Research Center on Aging
      Consumer Assessments Study. The sample included 1,056 subjects who reported use
      or nonuse of assistive devices. Of these subjects, 873 identified reasons for not
      using or being dissatisfied with certain assistive devices. Study participants
      owned a mean of 14.2 assistive devices, used 84.8% of the devices they owned, and
      were satisfied with 84.2% of the devices they owned. Devices were grouped into
      categories based on the type of impairment they addressed (hearing, vision,
      cognitive, and musculoskeletal/neuromotor). Study participants owned the largest
      number of devices in the musculoskeletal/neuromotor category (mean of 10.6
      devices). Devices in the hearing impairment category were rated lowest by
      participants in terms of satisfaction. Almost half of all reasons listed for not
      using certain assistive devices related to perceived lack of need.

PMID- 14651252
TI  - Efficacy of three head-pointing devices for a mouse emulation task.
AB  - Today, there are three competing technologies (exemplified by five products) to
      provide head-pointing mouse emulation. Since the manufacturers of each of these
      devices claims to provide similar functionality, it can be difficult for the
      clinician to decide which is the appropriate device for a client. The current
      study compares the functional performance of the three input technologies using
      three commercially available devices, the HeadMaster Plus, Tracker 2000, and
      Tracer. Each device was used to produce a series of drawings of similar
      complexity until the participants achieved a stable level of performance. The
      number of trials required to achieve mastery, the speed of drawing at mastery,
      and the accuracy of drawings was compared for the devices. In addition, the
      participants were asked about their subjective experience using the devices. Each
      of the three technologies was fastest for some participants, but the HeadMaster
      Plus produced the most consistently fast drawing times. Results indicated that
      although performance of the devices was similar, participant preference was
      driven by comfort more than by performance. The two fastest devices, the
      HeadMaster Plus and Tracer, both resulted in complaints regarding comfort,
      whereas the most comfortable device, the Tracker 2000, was preferred by
      participants although it was slightly slower in performance.

PMID- 14651253
TI  - Nicotine enhances neovascularization and promotes tumor growth.
AB  - Solid tumors require vascularization for their growth. Bone marrow-derived
      endothelial progenitor cells participate in tumor angiogenesis. Here, we show
      that nicotine markedly accelerated growth of colon cancer cells inoculated
      subcutaneously in mice but had no effect on proliferation of carcinoma cells in
      vitro. We found that the tumor growth was associated with increased
      vascularization of the tumor and that bone marrow-derived cells contributed to
      the formation of the new blood vessels. Our findings show that nicotine promotes
      tumor growth, at least in part, by stimulating tumor-associated
      neovascularization.

PMID- 14651254
TI  - Survivin reduces activation-induced T cell death in G1 phase.
AB  - A process termed activation-induced cell death (AICD) is responsible for
      peripheral T cell tolerance after negative selection of self-reactive T cells,
      and deletion of hyperactivated T cells following the immune response. Cells in G1
      phase of the cell cycle are most susceptible to AICD. We have investigated the
      relationship between the induction of AICD by phorbol 12-myristate 13-acetate
      plus ionomycin during the cell cycle and the expression of survivin, an inhibitor
      of the apoptosis protein (LAP) family. AICD was highly induced in cells of the
      human T cell line Jurkat E6.1 arrested in G1 phase, whereas survivin was hardly
      expressed in G1 and instead it was highly expressed in G2/M. Moreover, transient
      over-expression of survivin in G1 partially blocked the induction of AICD. These
      results suggest that survivin inhibits the induction of AICD, especially in G1
      phase.

PMID- 14651255
TI  - Degranulation and cytokine expression in human cord blood-derived mast cells
      cultured in serum-free medium with recombinant human stem cell factor.
AB  - Human cord blood-derived mast cells (HCMC) grown in medium with serum and
      recombinant human stem cell factor (rhSCF) with or without interleukin (IL)-6 are
      less mature than human skin mast cells (HSMC). We found that c-kit-positive HCMC
      cultured for 8-10 weeks with rhSCF in serum-free medium became sensitive to basic
      secretatogues and expressed the serine protease, chymase, which is preferentially
      expressed in HSMC. The HCMC release beta-hexosaminidase (beta-HEX) within 1 min
      of stimulation with compound 48/80 or substance P, and release was suppressed by
      pertussis toxin. Approximately 34% of the HCMC in the serum-free culture stained
      positively with chymase antibody. Chymase and c-kit levels, and responsiveness to
      basic secretagogues, increased substantially after an additional 2 weeks in a
      serum-free environment with rhIL-6 and rhSCF. Moreover, Fc(epsilon)RI-dependent
      activation of the HCMC resulted in induction of cytokines and cyclooxygenase-2.
      These results show that HCMC can differentiate into a phenotype morphologically
      and functionally similar to HSMC if exposed to SCF in serum-free medium.

PMID- 14651256
TI  - Discovering the interaction propensities of amino acids and nucleotides from
      protein-RNA complexes.
AB  - With the availability of many genome sequences, the mining of biological data is
      attracting much attention, most of it limited to the sequences of macromolecules.
      Sequence data are easy to analyze as they can be treated as strings of
      characters, whereas the structure of a macromolecule is much more complex. We
      developed a set of algorithms to analyze the structures of protein-RNA complexes
      at the atomic level and used them to analyze protein-RNA interactions using
      structural data on 51 protein-RNA complexes. The analysis revealed, among other
      things, that: (1) polar and charged amino acids have a strong tendency to
      interact with nucleotides, (2) arginine and asparagine tend to hydrogen bond with
      uracil, and (3) histidine favors uracil in water-mediated bonding with RNA. We
      analyzed a large set of structural data of protein-RNA complexes involving water
      mediated hydrogen bonds as well as direct hydrogen bonds. The interaction
      patterns discovered from the analysis provide useful information for predicting
      the structure of RNA that binds proteins, and of proteins that bind RNA.

PMID- 14651257
TI  - Interleukin-10 is up-regulated by prolactin and serum-starvation in cultured
      mammary epithelial cells.
AB  - The epithelial cells of the mammary gland go through a cycle of growth,
      differentiation, and involution during pregnancy. Recently, we found that
      interleukin-10 (IL-10) was induced at the involution stage and contributed to
      apoptosis in the mammary gland. To elucidate the role of the epithelial cells in
      involution, we examined IL-10 expression in an in vitro model of HC11 cells, in
      various culture conditions. IL-10 was weakly expressed early in growth but when
      the cells were induced to differentiate by insulin and dexamethasone expression
      increased slightly. Prolactin in combination with insulin and dexamethasone
      caused a further increase. To mimic apoptosis the culture was deprived of serum
      as well as hormones, and this resulted in a gradual increase in IL-10. In
      contrast with its ligand, the IL-10 receptor itself was not expressed in any
      conditions. We speculate that release of IL-10 from the epithelial cells recruits
      lymphocytes, which have IL-10 receptors on their cell membranes, and they in turn
      secrete death factors inducing apoptosis of the epithelial cells.

PMID- 14651258
TI  - GnRH-II analogs for selective activation and inhibition of non-mammalian and type
      II mammalian GnRH receptors.
AB  - Recently, we identified three types of non-mammalian gonadotropin-releasing
      hormone receptors (GnRHR) in the bullfrog (designated bfGnRHR-1-3), and a
      mammalian type-II GnRHR in green monkey cell lines (denoted gmGnRHR-2). All these
      receptors responded better to GnRH-II than GnRH-I, while mammalian type-I GnRHR
      showed greater sensitivity to GnRH-I than GnRH-II. In the present study, we
      designed new GnRH-II analogs and examined whether they activated or inhibited non
      mammalian and mammalian type-II GnRHRs. [D-Ala6]GnRH-II, with D-Ala substituted
      for Gly6 in GnRH-II, increased inositol phosphate (IP) production in cells stably
      expressing non-mammalian GnRHRs more effectively than native GnRH-II. However, it
      exhibited lower activity for mammalian type-I GnRHR than GnRH-I itself.
      Trptorelix-1, a GnRH-II antagonist, inhibited GnRH-induced IP production in cells
      expressing non-mammalian GnRHRs more effectively than Cetrorelix, a GnRH-I
      antagonist. Trptorelix-1, however, had lower potency for mammalian type-I GnRHR
      than Cetrorelix. Ligand-receptor binding assays revealed that [D-Ala6]GnRH-II and
      Trptorelix-1 have higher affinities for non-mammalian GnRHRs but lower affinities
      for mammalian type-I GnRHR than GnRH-II and Cetrorelix, respectively. Moreover,
      [D-Ala6]GnRH-II and Trptorelix-1 had a higher affinity for gmGnRHR-2 than GnRH-II
      and Cetrorelix, respectively. These results indicate that [D-Ala6]GnRH-II and
      Trptorelix-1 are highly effective agonist and antagonist, respectively, for non
      mammalian and type-II mammalian GnRHRs.

PMID- 14651259
TI  - Signaling via histamine receptors in cat duodenal smooth muscle cells.
AB  - Histamine produced concentration-dependent contractions in cat duodenal smooth
      muscle cells that were obtained by enzymatic digestion of smooth muscle with
      collagenase F. Pyrilamine, an H1 receptor antagonist, inhibited the contractile
      response while famotidine, an H2 receptor antagonist, augmented it. In cells with
      selectively preserved H1 receptors, produced by pretreatment with pyrilamine
      followed by inactivation of all unprotected receptors with N-ethylmaleimide,
      histamine-induced contraction was significantly augmented as compared with
      control cells. Pertussis toxin (PTX) had no effect on contraction, suggesting
      that the H1 receptor is coupled to a PTX-insensitive G protein. Gi2, Gi3, Go, Gs,
      and Gq subunits were present in cat duodenum, and histamine-induced contraction
      was inhibited by Gq antibody after cell permeabilization. Neomycin, a PLC
      inhibitor, inhibited the histamine-induced cell contraction, but not rhoCMB, a
      PLD inhibitor, or DEDA, a PLA2 inhibitor. Heparin, an IP3 receptor inhibitor,
      inhibited contraction whereas chelerythrine, a PKC inhibitor, had no effect. We
      conclude that histamine-induced contraction in cat duodenal smooth muscle cells
      is mediated by H1 receptors coupled to a PTX-insensitive Gq protein and results
      in activation of phosphatidylinositol-specific phospholipase C (PI-PLC).

PMID- 14651260
TI  - Renaturation of recombinant ErmSF and its refolding behavior.
AB  - ErmSF is one of four gene products responsible for the resistance of Streptomyces
      fradiae to the autogenous antibiotic, tylosin. It catalyzes the methylation of a
      single adenine residue (A2058) of 23S rRNA to produce dimethyl adenine from
      monomethyl adenine or unmodified adenine. This reduces the affinity of macrolide
      lincosamide-streptogramin B (MLS) antibiotics for the peptidyltransferase circle
      and confers resistance to these antibiotics. We earlier cloned ermSF from
      Streptomyces fradiae, ligated it into pET23b with a T7 promoter and transformed
      it into E. coli. The transformants were resistant to erythromycin, but most of
      the expressed protein was present as an inclusion body. In the present work, the
      protein was extracted from the inclusion bodies, solubilized with 6 M guanidine
      HCl, and purified by metal ion (Ni2+) affinity chromatography yielding 171 mg of
      denatured protein per liter of culture. Renaturation of the protein was achieved
      by step-wise removal of the guanidine-HCl. Most of the refolded protein appeared
      to assume the natural conformation, as judged by circular dichroism spectroscopy.
      The yield of refolded protein increased as the protein concentration in the
      renaturation medium was lowered, but the activity of the renatured protein tended
      to increase with protein concentration. The highest yield of renatured protein,
      107 mg/L of culture had 55% of the activity of the naturally folded protein.
      Refolding was also carried out by removing denaturant by a simple two-step
      dilution-dialysis method. With that method, the yield of the refolded protein was
      lower and the activity higher than with step-wise refolding. The yields and
      activities did not seem to be affected by the concentration of denaturant,
      suggesting that renaturation under the conditions employed occurred spontaneously
      with a strong tendency to fold to the native state, even though ErmSF contains
      two domains.

PMID- 14651261
TI  - Cloning and expression of mitochondrial MnSOD from the small radish (Raphanus
      sativus L.).
AB  - A cDNA clone for a mitochondrial MnSOD was isolated from a cDNA library derived
      from seedlings of the small radish (Raphanus sativus L.). The cDNA clone,
      RsMnSOD, encoded a polypeptide with a predicted molecular mass of 25.4 kDa and
      calculated pI of 8.77. Its deduced amino acid sequence was 93% homologous with
      MnSOD of Arabidopsis. RNA gel blot analysis showed that RsMnSOD transcripts were
      most abundant in leaves, followed by roots and hypocotyls, whereas transcripts of
      RsFeSOD and RsCu/ZnSOD were not detected in roots. The hypocotyls of germinated
      seedlings turned green and finally red in response to white light. These color
      changes were accompanied by increases in RsMnSOD and RsCu/ZnSOD mRNA. In
      addition, RsMnSOD expression was strongly induced by osmotic stress, moderately
      induced by phytohormones such as ABA and IAA, and not induced by xenobiotics
      other than cercosporin.

PMID- 14651262
TI  - Structural elements of dynamic RNA strings.
AB  - Short transient secondary structures form while RNA is being transcribed, and
      these become the initial sites for protein anchoring. The insulin gene transcript
      (IGT) of chain length 1,430 nucleotides can be folded into 92 stem-loops, at an
      average of one stem-loop per 15.5 nucleotides (range: 9-35). The 25
      hydroxyvitamin D3 1-alpha-hydroxylase gene transcript (HDHGT) of 4,825
      nucleotides can fold into 274 stem-loops, at one stem-loop per 17.6 nucleotides
      (range: 9-45). We found no differences in transient secondary structures between
      the exons of IGT and HDHGT but there were significant differences between the
      introns. RNA chain shortening by folding ranged from 2.57 to 9.6 fold.
      Contraction ratios for IGT were 2.79 for minimal contraction and 7.77 for maximal
      contraction, and for HDHGT 2.57 and 8.80 respectively. The maximal contraction
      ratios but not the minimal contraction ratios differed significantly between IGT
      and HDHGT. This implies that initial RNP fibril formation may proceed by shared
      mechanisms whereas the final degree of compaction can differ in different hnRNPs.
      Metastable co-transcriptional folding may be necessary for "chaperones"/"match
      makers" to refold the RNA correctly for splicing and other maturation process.
      Branch point sequences are not consistent and are not included in the analysis.
      However, 5' and 3' splice regions have more disordered secondary structures, and
      3' and 5' exon regions contain intrinsic snap-back complementarity that can bring
      3' and 5' nucleotides together for joining. Upon splicing, the remaining exons
      undergo no change except for a few stem-loops flanking the splice sites.

PMID- 14651263
TI  - Immunocytochemical localization of neurons containing the AMPA GluR2/3 subunit in
      the hamster visual cortex.
AB  - AMPA glutamate receptors play a crucial role in brain functions such as synaptic
      plasticity and development. We have studied the chemo-architecture of the AMPA
      glutamate receptor subtype GluR2/3 in the hamster visual cortex by
      immunocytochemistry and compared it with the distribution of the calcium-binding
      proteins, calbindin D28K and calretinin. Anti-GluR2/3-immunoreactive (IR) neurons
      were predominantly located in layers II/III, V, and VI, and the majority of the
      labeled neurons were round or oval. However, many pyramidal cells in layer V were
      also labeled. Two-color immunofluorescence revealed that none of the GluR2/3-IR
      neurons contained calbindin D28 K or calretinin. Thus specific layers of neurons
      express the GluR2/3 subunit and these do not correlate with expression of
      calbindin D28K and calretinin.

PMID- 14651264
TI  - Exoenzyme Tat-C3 inhibits association of zymosan particles, phagocytosis,
      adhesion, and complement binding in macrophage cells.
AB  - Phagocytosis by macrophages is most important in the initial stages of an immune
      response. Although RhoA regulates cell adhesion, its roles in the integrin
      related association of particles with macrophages and in phagocytosis are not
      clearly understood. We introduced C3 exoenzyme, a specific inhibitor of Rho, into
      J774A.1 macrophage cells fused with the 9 amino acid (49-57) transduction domain
      (RKKRRQRRR) of HIV-1 Tat. The presence of this Tat-C3 vector altered RhoA
      mobility on non-denaturing gels, indicating that Tat-C3 modified RhoA by ADP
      ribosylation. Uptake of (FITC)-conjugated serum-opsonized zymosan particles and
      adhesion to fibrinogen-coated plates were reduced as was the association of serum
      opsonized zymosan particles, and complement C3 and C3bi with the transfected
      cells. These results suggest that Rho regulates the activity of integrins that
      are involved in the association of particles with macrophages, phagocytosis,
      adhesion, and binding of complement C3 and C3bi.

PMID- 14651265
TI  - A rice isoflavone reductase-like gene, OsIRL, is induced by rice blast fungal
      elicitor.
AB  - We have isolated and characterized a rice isoflavone reductase-like gene, OsIRL,
      whose expression is induced by a fungal elicitor. The OsIRL cDNA contains 1203 bp
      with an open reading frame of 942 nucleotides encoding 314 amino acids. The
      deduced amino acid sequence of OsIRL has a putative pyridine nucleotide binding
      domain and is 68% homologous with the maize isoflavone reductase-like gene.
      Southern blot analysis revealed that OsIRL belongs to a small multigene family.
      Expression of OsIRL was induced by treatment with a fungal elicitor and jasmonic
      acid as well as by inoculation with rice blast fungus. Cycloheximide (1 microM),
      strongly inhibited the induction of OsIRL by the fungal elicitor, indicating that
      new protein synthesis is required. The protein kinase inhibitor, staurosporine (1
      microM), had little effect, but the phosphatase inhibitor, calyculin A (1
      microM), strongly inhibited induction. Treatment with salicylic acid (SA, 5 mM)
      strongly inhibited expression of OsIRL in response to fungal elicitor and JA,
      while abscisic acid (ABA, 200 microM) also strongly antagonized OsIRL induction
      by JA, but had only a weak effect on induction by the fungal elicitor. These
      results suggest that the expression of OsIRL is positively regulated by
      phytohormones such as JA, and negatively by phytohormones such as SA, ABA.

PMID- 14651266
TI  - Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats
      after transient forebrain ischemia.
AB  - Neurogenesis in the dentate gyrus occurs throughout life. We observed regional
      differences in neurogenesis in the dentate gyrus of adult rats following
      transient forebrain ischemia. Nine days after ischemic-reperfusion or sham
      manipulation, rats were given 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU), a
      marker for dividing cells. They were killed 1 or 28 days later to distinguish
      between cell proliferation and survival. Neurogenesis was evaluated by BrdU
      incorporation as well by identifying neuronal and glial markers in six regions of
      the dentate gyrus: rostral, middle and caudal along the rostrocaudal axis, each
      further divided into suprapyramidal and infrapyramidal blade subregions. In
      control rats BrdU-positive cells in the rostral subregions were significantly
      lower in the suprapyramidal than in the infrapyramidal blades at both 1 and 28
      days after BrdU injection. One day after injection, BrdU-positive cells had
      increased more in five of the subregions in the ischemic rats than in the
      controls, the exception being the suprapyramidal blade of the rostral subregion.
      At 28 days after BrdU injection, numbers of BrdU-positive cells were higher in
      four subregions in the ischemic group, the exceptions being the rostral
      suprapyramidal and middle infrapyramidal blades. At 28 days after BrdU injection,
      the percentages of BrdU positive cells that expressed a neuronal marker (NeuN)
      were the same in the dentate granule cell layers of ischemic and control rats.
      Our data thus demonstrate regional differences in enhanced neurogenesis in the
      dentate gyrus of adult rats after transient forebrain ischemia.

PMID- 14651267
TI  - Cloning and expression of cryptochrome2 in the bullfrog (Rana catesbeiana).
AB  - Cryptochromes (CRYs) are non-opsin photoactive pigments that have recently been
      implicated in circadian photo-entrainment in humans, mice and Drosophila. In
      order to study the mechanism of circadian rhythm in amphibians, we have cloned
      and characterized a Rana cryptochrome in the bullfrog. We isolated a cDNA of
      about 2.1 kb from a bullfrog brain cDNA library by screening with a partial cry2
      cDNA probe obtained by RT-PCR using degenerate primers. The cloned Rana cry2 cDNA
      has a complete single open-reading frame consisting of 323 amino acids, and its
      deduced amino acid sequence has a high degree of homology with human and mouse
      CRY2. Interestingly, we also isolated two other cry2 cDNAs, which may be splicing
      variants. Rana cry2 is expressed in all tissues as a 2.2 kb transcript. It is
      particularly highly expressed in the brain and ovaries, and also showed seasonal
      variation in expression in ovarian tissue. To examine its involvement in
      circadian rhythm, we tested whether expression in brain tissue followed a light
      dark cycle, and found that expression was higher in the dark than in the light.
      Rana cry2 should therefore, be useful for studying circadian rhythms in
      seasonally breeding wild animals.

PMID- 14651268
TI  - Macrophage-derived TGF-beta1 induces IgA isotype expression.
AB  - TGF-beta1 is a potent IgA isotype switching factor. However the cell population
      that generates the TGF-beta is not known. In this study, we examined the origin
      of the TGF-beta1 that is secreted by LPS-activated murine total spleen cell
      cultures and that is responsible for IgA isotype switching. Treatment with anti
      TGFbeta1 antibody decreased IgA secretion 2 fold in these cultures and caused a 5
      fold decrease in the number of IgA secreting cells. In Mphi-depleted spleen cell
      populations, this IgA response was markedly reduced and anti-TGFbeta1 antibody
      had no additional effect on IgA production. The inference that Mphi-derived TGF
      beta1 is responsible for the isotype switching is supported by observations with
      the macrophage line, P388D1. LPS, particularly in the presence of IFN-gamma,
      induced P388D1 cells to secrete active TGF-beta1. The supernatant from such an
      activated P388D1 culture, in combination of IL-2, stimulated IgA secretion and
      this effect was abolished by anti-TGFbeta1 antibody.

PMID- 14651269
TI  - The effect of ER stress on activity-dependent induction of brain-derived
      neurotrophic factor exon III.
AB  - Neuronal activity promotes neuronal survival and increases synaptic strength.
      These effects are primarily mediated by influx of calcium through L-type calcium
      channels during membrane depolarization. This activates the transcription factor
      CREB by phosphorylating it on Ser-133 and induces several genes including BDNF
      exon III that play important roles in activity-dependent neuronal survival. Since
      ER stress is known to perturb intracellular calcium signaling, we examined
      whether it attenuated depolarization-induced CREB Ser-133 phosphorylation and
      BDNF exon III expression in PC12 cells. ER stress induced by tunicamycin, beta
      mercaptoethanol, or thapsigargin did not reduce depolarization-induced CREB Ser
      133 phosphorylation. However it did suppress the induction of BDNF exon III by
      membrane depolarization, indicating that it exerts this effect by blocking a
      pathway distinct from CREB Ser-133 phosphorylation.

PMID- 14651270
TI  - Downregulation of voltage-gated potassium channel alpha gene expression by
      axotomy and neurotrophins in rat dorsal root ganglia.
AB  - Injury to peripheral nerves causes a neuropathic pain which is difficult to
      relieve, but the underlying mechanism remains largely unknown. In previous
      studies we reported that voltage-gated potassium (Kv) channel alpha genes are
      downregulated in the dorsal root ganglia (DRG) following chronic constriction of
      the sciatic nerve [Kim et al. (2002)], suggesting a relationship between
      electrical abnormalities of the injured neurons and Kv gene expression. Here, we
      examined expression of the Kv 1.2, 1.4, and 4.2 genes in the DRG following
      transection of the sciatic nerve, and investigated the effect of nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)
      on expression of those mRNAs, using the reverse transcription-polymerase chain
      reaction. Expression of these mRNAs was reduced by axotomy and by exposure to
      BDNF, and NT-3 treatment. However no significant change was detected following
      NGF treatment. Our findings suggest that downregulation of Kv channel gene
      expression in DRG neurons by neurotrophins may play an important role in long
      term changes of neuronal excitability following nerve injury.

PMID- 14651271
TI  - A genotype-specific pollen gene associated with self-incompatibility in
      Lycopersicon peruvianum.
AB  - Self-incompatibility is a genetically controlled process used to prevent self
      pollination. We report here the characterization of pollen cDNA clones of
      Lycopersicon peruvianum, and the identification of a genotype-specific pollen
      factor involved in self-incompatibility. To identify the latter, differential
      mRNA display RT-PCR was performed on pollen cDNAs from S12Sa and S11Sa genotypes.
      We isolated four cDNA fragments expressed preferentially in S12Sa pollen, and
      screened a cDNA library from S12Sa pollen with the four cDNA fragments to isolate
      the corresponding full length cDNAs. One of the four isolated cDNAs encoded part
      of an actin depolymerizing factor protein that we named LpADF. LpADF is highly
      homologous to actin depolymerizing factors of Arabidopsis thaliana, Lilium
      longiflorum, and Zea mays. RNA blot analysis revealed that LpADF is only
      expressed in mature pollen of the S12Sa genotype, and is therefore a candidate
      pollen factor in the gametophyte self-incompatibility system of L. peruvianum.

PMID- 14651272
TI  - X-ray crystallographic studies of HemK from Thermotoga maritima, an N5-glutamine
      methyltransferase.
AB  - The enzyme HemK (or PrmC) is one of the first identified methyltransferases that
      modify glutamine. It methylates the highly conserved GGQ motif in class I release
      factors (RF1 and RF2) in Escherichia coli. HemK from Thermotoga maritima was over
      expressed and crystallized in the presence of S-adenosylmethionine at 296 K using
      ammonium sulfate as the precipitant. X-ray diffraction data were collected to 2.5
      A resolution from a native crystal. The crystal is orthorhombic, belonging to the
      space group I222 (or I2(1)2(1)2(1)), with unit-cell parameters of a = 104.24, b =
      118.73, and c = 146.62 A. Two (or three) monomers of recombinant HemK are likely
      to be present in the crystallographic asymmetric unit, giving a V(M) of 3.62 A3
      Da(-1) (or 2.41 A3 Da(-1)), with a solvent content of 62.7% (or 44.0%).

PMID- 14651273
TI  - The incidence of bacteremia in endodontic manipulation: preliminary report. 1960.

PMID- 14651274
TI  - Roentgenographic and direct observation of experimental lesions in bone: I. 1961.

PMID- 14651275
TI  - Roentgenographic and direct observation of experimental lesions in bone: II.
      1961.

PMID- 14651276
TI  - Cognitive dissonance in endodontics. 1965.

PMID- 14651277
TI  - Paget's disease.
AB  - A review of the signs, symptoms, and treatment of Paget's disease is presented.
      Paget, or osteitis deformans, is a chronic, progressive, bone disease of viral
      etiology. Recent investigations about the causative agent of this disorder have
      implicated the measles virus of the paramyxovirus family. Additional studies have
      demonstrated that abnormal virus-infected osteoclasts generate interleukin (IL)
      6, a resorptive cytokine from the bone marrow of patients with Paget's bone
      disease.

PMID- 14651278
TI  - Anesthetic efficacy of the supplemental X-tip intraosseous injection in patients
      with irreversible pulpitis.
AB  - The purpose of this study was to determine the anesthetic efficacy of the
      supplemental intraosseous injection, using the X-tip system in an apical
      location, in mandibular posterior teeth diagnosed with irreversible pulpitis when
      the conventional inferior alveolar nerve block failed. Thirty-three emergency
      patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth,
      received an inferior alveolar nerve block and had moderate-to-severe pain on
      endodontic access. The X-tip system was used to administer 1.8 ml of 2% lidocaine
      with 1:100,000 epinephrine. The X-tip injection site was 3- to 7-mm apical to the
      mucogingival junction of the affected tooth. Success of the X-tip intraosseous
      injection was defined as none or mild pain on endodontic access or initial
      instrumentation. The results of this study demonstrated that 6 of 33 (18%) X-tip
      injections resulted in backflow of anesthetic solution into the oral cavity; none
      were successful in obtaining anesthesia. Twenty-seven of the remaining 33 X-tip
      injections (82%) were successful. We conclude that when the inferior alveolar
      nerve block fails to provide profound pulpal anesthesia, the X-tip system, when
      used in an apical location and when there was no backflow of the anesthetic
      solution into the oral cavity, was successful in achieving pulpal anesthesia in
      mandibular posterior teeth of patients presenting with irreversible pulpitis.

PMID- 14651279
TI  - Direct capping with four different materials in humans: histological analysis of
      odontoblast activity.
AB  - Pulp inflammation in restored teeth is mainly due to the presence of bacteria or
      bacterial products introduced by microleakage around the restoration or to the
      material toxicity. Recent knowledge has permitted a precise identification of the
      risks for pulpal irritation associated with adhesive materials and procedures.
      The purpose of this work was to evaluate the cellular events that occur in direct
      pulp exposure capped using different materials. Twenty-four vital teeth without
      caries, scheduled for extraction for orthodontic reasons, were selected. After a
      control of the hemostasis, each pulp was directly capped with a different
      material. The samples were randomly divided into four groups of six specimens
      each: group I: dental-bonding agent (Solist) followed by resin composite
      (Ecusit); group II: dental adhesive (Prompt) and resin composite (Pertac II);
      group III: traditional calcium hydroxide (Dycal) plus resin composite (Ecusit);
      group IV: light-curing calcium hydroxide (Ultrablend Plus) and amalgam
      (Dentsply). After 15 days the teeth were extracted, immediately fixed in 10%
      buffered formalin, embedded in resin (7200 Technovit), and prepared for thin
      ground sections with Precise 1 System. In the specimens of all groups, there were
      active odontoblasts near the composite resins and no newly formed dentin. Small
      quantities of inflammatory cells were present. A 1- to 3-microm layer zone of
      necrosis was present. In conclusion, all materials tested in this study induced
      similar tissue responses.

PMID- 14651280
TI  - Pseudoramibacter alactolyticus in primary endodontic infections.
AB  - A nested polymerase chain reaction (PCR)-based method was used to directly survey
      samples taken from primary endodontic infections for the occurrence of
      Pseudoramibacter alactolyticus. Identification by nested PCR was performed in
      root-canal samples from teeth associated with asymptomatic periradicular lesions
      or acute apical periodontitis, and in pus samples from acute periradicular
      abscesses. DNA was extracted from the samples and initially amplified using
      universal 16S rDNA primers. A second round of amplification used the first PCR
      products to detect a specific fragment of P. alactolyticus 16S rDNA. P.
      alactolyticus was detected in 76% of root-canal samples from teeth showing
      asymptomatic periradicular lesions, in 60% of samples taken from root canals
      associated with acute apical periodontitis, and in 32% of pus samples aspirated
      from acute periradicular abscesses. No significant association of this species
      with clinical symptoms was observed (p > 0.01). In general, P. alactolyticus
      occurred in 56% of samples taken from infections of endodontic origin. The high
      prevalence of P. alactolyticus in infections of endodontic origin as detected by
      nested PCR in this study, and its apparent pathogenicity, particularly in mixed
      infections, indicate that this bacterial species is a candidate endodontic
      pathogen that can participate in the etiology of different forms of periradicular
      diseases.

PMID- 14651281
TI  - Clinical and radiographic evaluation of root-canal obturation with obtura II.
AB  - This study evaluated clinical and radiographic healing of 236 root-canal
      treatments in 131 cases obturated with the Obtura II system. One operator
      performed all canal preparation and obturation with sealer. A standardized apical
      coronal preparation technique instrumented all canals. Clinical symptoms,
      periodontal condition, and radiographic findings were evaluated at 3, 6, and 12
      months. Radiographs taken immediately postobturation were compared to recall
      radiographs. The level of the final root filling was classified as short (more
      than 2 mm short of the apex), flush (within 2 mm), or over (beyond) in 12.7%,
      81.4%, and 5.9% of cases, respectively. More than 96% of cases were treated
      successfully by the Obtura II system. Where roots were filled flush, over, or
      short, lesions healed in 97%, 93%, and 93% of cases, respectively, with no
      significant differences (p < 0.05). Root filling excess had no impact on the
      healing process.

PMID- 14651282
TI  - In vitro neurotoxic evaluation of root-end-filling materials.
AB  - Root-end-filling materials have been tested for toxicity on several cell types,
      but their toxicity has not been tested on neurons. In this study we evaluated the
      neurotoxicity in murine cerebral cortical cell cultures of four commonly used
      root-end-filling materials: mineral trioxide aggregate, amalgam, Super EBA, and
      Diaket. Standardized amounts of each material were placed on culture-well
      inserts, allowing the material to be exposed to the culture bathing media without
      causing physical disruption of the cells. Cell death was quantified by assaying
      release of the cytosolic enzyme lactate dehydrogenase. Exposure of cortical
      cultures to freshly mixed or 7-day-old MTA did not cause significant neuronal
      death, whereas exposure to freshly mixed or 7-day-old amalgam, Super EBA, and
      Diaket resulted in significant neuronal death (p < .05). Thus, each material,
      except for mineral trioxide aggregate, can induce neurotoxicity, even when
      allowed to set thoroughly.

PMID- 14651283
TI  - Effect of MTAD on flexural strength and modulus of elasticity of dentin.
AB  - The purpose of this study was to evaluate the effect of MTAD on the flexural
      strength and modulus of elasticity of dentin. Dentin bars were randomly assigned
      to eight groups treated with various concentrations of NaOCl (5.25%, 2.65%,
      1.31%, 0.66%), 17% EDTA, MTAD, saline, or according to a clinical protocol with
      1.3% NaOCl and then 5 min of MTAD. Specimens were subjected to flexural strength
      and modulus of elasticity tests. Two-sample t test (alpha = 0.05) showed no
      statistically significant differences between various groups except for a
      reduction in flexural strength for the 2-h MTAD group (p = 0.002) and the EDTA
      group (p = 0.002). A significant reduction of modulus of elasticity for the 2-h
      MTAD group (p < 0.001), EDTA group (p < 0.001), and 0.6% NaOCl (p < 0.002) also
      was noted. There was no significant difference in flexural strength and modulus
      of elasticity between the dentin bars exposed to saline or MTAD when applied
      according to the clinical protocol (p > 0.05). These results indicate that MTAD
      can be used as prescribed for clinical use without affecting the physical
      properties of the dentin.

PMID- 14651284
TI  - Radiopacity of endodontic sealers: development of a new method for direct
      measurement.
AB  - Radiopacity is an essential attribute of endodontic filling materials. It is
      important to see clearly the root canal filling to detect its presence, extent,
      and apparent condensation. National and international standards require a minimal
      radiopacity equivalent to 3 or 4 mm of aluminum, yet some products made by
      reputed companies do not meet this requirement. The result may be unjustified
      downgrading of clinical cases. The purpose of this investigation was 2-fold: to
      develop a novel and easily reproducible technique for assessing the radiopacity
      of endodontic sealers and to apply it to measure the opacity of 21 current
      cements poured in 6- x 1-mm wells. As in the currently recommended technique, the
      standardized samples are radiographed alongside an aluminum stepwedge but instead
      of using an optical densitometer to measure the density and then calculate the
      radiopacity, the image is digitized. The gray pixel value of the test material is
      compared with the stepwedge, using computer software, to find the corresponding
      step. The opacity of the samples ranged from 1.6 mm to more than 11 mm of
      aluminum. The technique can be advanced to a dry, chemical-less variant by using
      radiation captors, as for periapical X-rays, instead of film.

PMID- 14651285
TI  - Evaluation of an ultrasonic technique to remove fractured rotary nickel-titanium
      endodontic instruments from root canals: an experimental study.
AB  - The use of nickel-titanium rotary instruments in endodontic practice is
      increasing. One frequently mentioned problem is fracture of an instrument within
      the root canal. To date, there is no consistently safe and successful technique
      for removing these fractured instruments. This study evaluates the use of an
      ultrasonic technique to remove fractured rotary nickel-titanium instruments from
      narrow, curved canals in both simulated (resin blocks) and mesiolingual canals of
      extracted mandibular first molars. A technique using ultrasonic tips, combined
      with the creation of a "staging platform" and the use of the dental operating
      microscope, was consistently successful and safe at removing fractured rotary
      nickel-titanium instruments from curved root canals, when some part of the
      fractured instrument segment was located in the straight portion of the canal.
      When the fractured instrument segment was located entirely around the curve, the
      success rate was significantly decreased and major canal damage often occurred.

PMID- 14651286
TI  - Evaluation of an ultrasonic technique to remove fractured rotary nickel-titanium
      endodontic instruments from root canals: clinical cases.
AB  - The removal of fractured rotary nickel-titanium instruments from small, curved
      root canals is one of the most complex operative procedures in endodontics. There
      have been many different devices and techniques developed to remove fractured
      instruments, but none are consistently successful and all show a high incidence
      of canal damage such as perforation. A technique using a staging platform and the
      use of modern ultrasonic tips with direct visualization through a dental
      operating microscope has recently been evaluated. The use of this technique in
      clinical practice is described in 24 cases and illustrated by 3 cases.

PMID- 14651287
TI  - Paresthesia associated with endodontic treatment of mandibular premolars.
AB  - The objective of this retrospective study was to determine how often paresthesia
      occurs and to examine the role of the anatomy of the inferior alveolar nerve
      (IAN). The study took the form of a review of the records of the endodontic
      department at the Creighton University School of Dentistry, a literature review,
      and cadaver dissections. The result showed that of 6313 teeth treated during a 7
      yr period, 832 were mandibular premolar teeth. The eight reported cases of
      paresthesia in that group reflected an incidence of 0.96%. Observations of
      dissected human-cadaver mandibles indicated that the paresthesias of the mandible
      could be related to the confinement of the IAN within the limits of the mandible.
      It was concluded that these paresthesias were related to the intrabony course of
      the IAN through the mandible, which contributed to the paresthesia symptoms.

PMID- 14651288
TI  - Orbital pain and headache secondary to overfilling of a root canal.
AB  - A 35-yr-old woman was referred to the Istanbul University, Faculty of Dentistry,
      Oral Surgery Department with complaints of orbital pain and headache. Panoramic
      radiographs showed overfilling of a maxillary premolar, which caused a
      perforation in the maxillary sinus floor. The etiology, clinical manifestations,
      and treatment of this complication are discussed with emphasis on early surgical
      intervention to decrease the risk of a superimposed aspergillosis infection.

PMID- 14651289
TI  - Vestibular surgical access to the palatine root of the superior first molar: "low
      dose cone-beam" CT analysis of the pathway and its anatomic variations.
AB  - Apicoectomy of the superior first molar palatine root until recently involved
      relatively destructive and laborious surgery because of the palatal access route,
      which not only necessitates an extensive flap, but also the readying of
      procedures required to deal with a possible hemorrhage from the palatine artery.
      With the advent of operative microscopy, endodontic surgery has become more
      precise and less invasive and its technical potential has increased; a possible
      innovative surgical technique may entail vestibular root access. The possibility
      of using low-dose, low-cost computed tomography (CT) dedicated to the jaw to
      obtain anatomic information to plan apicoectomy via the vestibular approach was
      evaluated; 31 patients were referred to CT with the NewTom apparatus. In 43
      superior first molars, the mean distance of the palatine root from the external
      vestibular cortex was measured, and the frequency that the maxillary sinus
      lateral recess lay between the roots was determined. The mean root apex
      vestibular cortex distance was 9.73 mm. In 25% of cases the maxillary sinus
      recessus lay between vestibular and palatine roots. CT may play an important role
      in optimizing palatine root apicoectomy through vestibular access, with regard to
      precision and preventing complications, with relatively low biological and
      economic cost, also possibly contributing to the affirmation of this new surgical
      procedure.

PMID- 14651290
TI  - Maturogenesis: is it a new concept?
AB  - The treatment of an undeveloped (immature) tooth with a carious exposure has been
      reported extensively in the literature. The main objective of treatment is to
      provide vital pulp therapy to allow continued development of root dentin in the
      hope that the root will attain full maturity. A case report is presented that
      illustrates root development (maturogenesis), not just closure of the apex
      (apexogenesis). A direct pulp cap was performed after a carious pulp exposure
      using calcium hydroxide with iodoform paste. The crown was restored with a glass
      ionomer/composite resin cement.

PMID- 14651291
TI  - Where is our evidence?

PMID- 14651292
TI  - Does jugde activate COURT? Transposed-letter similarity effects in masked
      associative priming.
AB  - Transposed-letter (TL) nonwords (e.g., jugde) can be easily misperceived as
      words, a fact that is somewhat inconsistent with the letter-position-coding
      schemes employed by most current models of visual word recognition. To examine
      this issue further, we conducted four masked semantic/associative priming
      experiments, using a lexical decision task. In Experiment 1, the related primes
      could be words, TL-internal nonwords, or replacement-letter (RL) nonwords (e.g.,
      judge, jugde, or judpe, respectively; the target would be COURT). Relative to an
      unrelated condition, masked TL-internal primes produced a significant
      semantic/associative priming effect, an effect that was only slightly smaller
      than the priming effect for word primes. No effect, however, was observed for RL
      nonword primes. In Experiment 2, the TL-nonword primes were created by switching
      the two final letters of the primes (e.g., judeg). The results again showed a
      semantic/associative priming effect for word primes, but not for TL-final nonword
      primes or for RL-nonword primes. Experiment 3 replicated the associative/semantic
      priming effect for TL-internal nonword primes, with, again, no effect for TL
      final nonword primes. Finally, Experiment 4 again failed to yield a priming
      effect for TL-final nonword primes. The implications of these results for the
      choice of a letter-position-coding scheme in visual word recognition models are
      discussed.

PMID- 14651293
TI  - Number-of-features effects and semantic processing.
AB  - Participants list many semantic features for some concrete nouns (e.g., lion) and
      fewer for others (e.g., lime; McRae, de Sa, & Seidenberg, 1997). Pexman, Lupker,
      and Hino (2002) reported faster lexical decision and naming responses for high
      number of features (NOF) words than for low-NOF words. In the present research,
      we investigated the impact of NOF on semantic processing. We observed NOF effects
      in a self-paced reading task when prior context was not congruent with the target
      word (Experiment 1) and in a semantic categorization task (concrete vs. abstract;
      Experiment 2A). When we narrowed our stimuli to include high- and low-NOF words
      from a single category (birds), we found substantial NOF effects that were
      modulated by the specificity of the categorization task (Experiments 3A, 3B, and
      3C). We argue that these results provide support for distributed representation
      of word meaning.

PMID- 14651294
TI  - Semantic and phonological influences on the processing of words and
      pseudohomophones.
AB  - In two experiments, we investigated the relationship between semantics and
      phonology in the lexical decision task. In the first experiment, lexical
      decisions to words with large semantic neighborhoods were faster than those to
      words with sparse semantic neighborhoods. Conversely, this effect of semantic
      neighborhood was reversed for pseudohomophones (e.g., nale). That is,
      pseudohomophones based on words with large semantic neighborhoods took longer to
      reject than did those based on words with sparse semantic neighborhoods. In the
      second experiment, we found the magnitude of the semantic neighborhood effect for
      words to be a function of nonword foil type. Taken together, these results
      indicate that semantic neighborhood size affects processing of both words and
      pseudohomophones, and that the effect of semantic neighborhood size for words is
      more pronounced when pseudohomophone foils are employed. These effects are
      discussed in terms of a model in which the orthographic, phonological, and
      semantic systems are fully interactive.

PMID- 14651295
TI  - Cross-task strategic effects.
AB  - When easy and difficult items are mixed together, their reading aloud latencies
      become more homogeneous relative to their presentation in unmixed ("pure")
      conditions (Lupker, Brown, & Colombo, 1997). We report two experiments designed
      to investigate the nature of the mechanism that underlies this list composition,
      or blocking, effect. In Experiment 1, we replicated Lupker et al.'s (1997)
      blocking effect in the reading aloud task and extended these findings to the
      visual lexical decision task. In Experiment 2, we found that blocking effects
      generalized across tasks: The characteristics of stimuli in a visual lexical
      decision task influenced reading aloud latencies, and vice versa, when visual
      lexical decision and reading aloud trials were presented alternately in the same
      experiment. We discuss implications of these results within time-criterion
      (Lupker et al., 1997) and strength-of-processing (Kello & Plaut, 2000, 2003)
      theories of strategic processing in reading.

PMID- 14651296
TI  - Experimental manipulations of the phenomenology of memory.
AB  - We investigated the effects of visual input at encoding and retrieval on the
      phenomenology of memory. In Experiment 1, participants took part in events with
      and without wearing blindfolds, and later were shown a video of the events.
      Blindfolding, as well as later viewing of the video, both tended to decrease
      recollection. In Experiment 2, participants were played videos, with and without
      the visual component, of events involving other people. Events listened to
      without visual input were recalled with less recollection; later adding of the
      visual component increased recollection. In Experiment 3, participants were
      provided with progressively more information about events that they had
      experienced, either in the form of photographs that they had taken of the events
      or narrative descriptions of those photographs. In comparison with manipulations
      at encoding, the addition of more visual or narrative cues at recall had similar
      but smaller effects on recollection.

PMID- 14651297
TI  - Belief and recollection of autobiographical memories.
AB  - In three experiments, undergraduates rated autobiographical memories on scales
      derived from existing theories of memory. In multiple regression analyses,
      ratings of the degree to which subjects recollected (i.e., relived) their
      memories were predicted by visual imagery, auditory imagery, and emotions,
      whereas ratings of belief in the accuracy of their memories were predicted by
      knowledge of the setting. Recollection was predicted equally well in between- and
      within-subjects analyses, but belief consistently had smaller correlations and
      multiple regression predictions between subjects; individual differences in the
      cognitive scales that we measured could not account well for individual
      differences in belief. In contrast, measures of mood (Beck Depression Index) and
      dissociation (Dissociative Experience Scale) added predictive value for belief,
      but not for recollection. We also found that highly relived memories almost
      always had strong visual images and that remember/know judgments made on
      autobiographical memories were more closely related to belief than to
      recollection.

PMID- 14651298
TI  - Why are some people more knowledgeable than others? A longitudinal study of
      knowledge acquisition.
AB  - The purpose of this study was to investigate correlates of knowledge acquisition
      within a real-world domain-basketball. The study employed a longitudinal design
      and involved two sessions, with approximately 2.5 months between sessions.
      Session 1 occurred near the beginning of the men's college basketball season, and
      Session 2 occurred after the season. There was an indirect effect of interest in
      basketball on new basketball knowledge, via exposure to domain-relevant
      information. In addition, prior basketball knowledge had a strong effect on new
      basketball knowledge distinct from an influence through basketball exposure. This
      finding suggests that prior knowledge may provide a framework into which new
      knowledge can be integrated. By contrast, there was no effect of fluid
      intelligence on new basketball knowledge. Although somewhat surprising given
      evidence that this aspect of intelligence may play a role in the acquisition of
      certain types of knowledge, this finding accords with the view that knowledge is
      a major determinant of various aspects of cognitive functioning, including
      learning.

PMID- 14651299
TI  - Delaying judgments of learning affects memory, not metamemory.
AB  - Judgments of learning (JOLs) for cue-target word pairs correlate particularly
      well with later target recall when made under conditions that permit delayed
      attempts to retrieve the targets--the delayed-JOL effect. Metamemory theories
      claim that memory monitoring improves under these conditions. However, another
      theory--the memory hypothesis--claims that the correlation increases because
      retrieved items receive a boost in recall from spaced study and are assigned high
      JOLs, whereas unretrieved items receive no spaced study and, therefore, no boost
      in recall and, consequently, are assigned low JOLs. When we eliminated
      differences in spaced study by reexposing word pairs following their JOLs, the
      delayed-JOL effect disappeared, supporting the memory hypothesis.

PMID- 14651300
TI  - Testing a conceptual locus for the inconsistent object change detection advantage
      in real-world scenes.
AB  - Changes to objects that are inconsistent with the scene in which they appear are
      detected more accurately than changes to consistent objects. In three
      experiments, we tested whether this inconsistent object advantage derives from
      the differential retention of conceptual codes generated from a brief view of a
      real-world scene in accordance with a conceptual short-term memory (CSTM)
      hypothesis. A scene was presented for 250 msec, followed by a brief mask and a
      test scene in which a target object was either changed or not changed. In
      Experiment 1, changes that altered conceptual content (object deletion) were
      contrasted with visual changes (left-right orientation changes). In Experiment 2,
      the duration of the mask was manipulated to vary the amount of time available for
      conceptual consolidation of the initial scene. In Experiment 3, the type of mask
      was manipulated: Either a meaningless pattern mask or a meaningful, and thus
      conceptually disruptive, scene was shown. The inconsistent object advantage was
      obtained in each experiment, yet in none was it modulated in the direction
      predicted by the CSTM hypothesis. Instead, the inconsistent object advantage is
      likely to be caused by contextual influence on memory for visual object
      representations.

PMID- 14651301
TI  - Updating space during imagined self- and array translations.
AB  - Previous work has demonstrated superior spatial updating performance during
      imagined viewer rotation versus imagined object/array rotation. Studies have also
      suggested that rotations are more difficult to process than translations. In
      three studies, we examined whether the advantage seen for updating during
      imagined self-rotations would generalize to translations. The participants
      updated the positions of objects in a line extending either to the front and back
      of the viewer or to the right and left after imagining viewer or array
      translation. Experiments 1 and 2 replicated the effects seen in imagined rotation
      tasks. A response time and accuracy advantage was found for imagined viewer
      translation versus imagined array translation. In Experiment 3, we directly
      compared real and imagined self- and array translations and demonstrated an
      advantage for real versus imagined array translation. The results suggest that
      the advantage for imagined viewer transformations is not a function of the
      specific transformation, but rather of the ability to imagine and predict the
      outcome of a moving frame of reference.

PMID- 14651302
TI  - The positivity proportion effect: a list context effect in masked affective
      priming.
AB  - In the evaluative decision task, participants decide whether target words denote
      something positive or negative. Positive and negative prime words are known to
      engender so-called affective priming effects in this task. Primes were sandwich
      masked, and the proportion of positive to negative target words was manipulated.
      In Experiment 1, prime valence and positivity proportion interacted, so that
      primes of the less frequently presented target valence caused larger priming
      effects. Experiment 2 rendered an explanation of this interaction in terms of
      response bias unlikely, Experiment 3 ruled out a peripheral locus of the effect,
      and Experiment 4 ruled out an account in terms of stimulus repetition. The effect
      is explained by means of an attentional bias favoring the rare kind of valence.

PMID- 14651303
TI  - Probability judgment and subadditivity: the role of working memory capacity and
      constraining retrieval.
AB  - In this research, we examined the role that individual differences in working
      memory (WM) capacity, the strength of alternatives, and time constraints play in
      probability judgment and subadditivity. With a laboratory-based learning task,
      Experiment 1 revealed that the degree to which participants' probability
      judgments were subadditive was negatively correlated with a measure of WM
      capacity, even when variance due to short-term memory capacity was removed. In
      addition, participants were more subadditive when the viable alternatives were
      all rather weak. Experiment 2 extended the WM-capacity-subadditivity correlation
      to a population judgment task and revealed that subadditivity increases when the
      judgment task is performed under time constraints. Results support a model that
      assumes that people make probability judgments by comparing the focal hypothesis
      with relevant alternatives retrieved from long-term memory and that people high
      in WM span include more alternatives in the comparison process. Time constraints
      are assumed to truncate the alternative generation process, leading to fewer
      alternatives being recalled from long-term memory.

PMID- 14651304
TI  - Object-based attentional selection can modulate the Stroop effect.
AB  - The Stroop (1935) effect is the inability to ignore a color word when the task is
      to report the ink color of that word (i.e., to say "green" to the word RED in
      green ink). The present study investigated whether object-based processing
      contributes to the Stroop effect. According to this view, observers are unable to
      ignore irrelevant features of an attended object (Kahneman & Henik, 1981). In
      three experiments, participants had to name the color of one of two superimposed
      rectangles and to ignore words that appeared in the relevant object, in the
      irrelevant object, or in the background. The words were congruent, neutral, or
      incongruent with respect to the correct color response. Words in the irrelevant
      object and in the background produced significant Stroop effects, consistent with
      earlier findings. Importantly, however, words in the relevant object produced
      larger Stroop effects than did the other conditions, suggesting amplified
      processing of all the features of an attended object. Thus, object-based
      processing can modulate the Stroop effect.

PMID- 14651305
TI  - Pediatric peripheral i.v. insertion success rates.
AB  - Determination of an acceptable practice standard for peripheral intravenous (PIV)
      insertion as well as insertion success rates of inpatient medical/surgical
      registered nurse (RN) staff at Children's Hospital, Omaha, NE, was examined. The
      prospective study consisted of a non-randomized sample of 249 total i.v.
      placements. The inpatient medical/surgical registered nurse (RN) staff and
      patients were used as study participants. The data were collected on three
      separate occasions over 20 months by self-report. The cumulative insertion data
      revealed 53% successful PIV cannulation on the first attempt, 67% within two
      attempts, and 91% within four attempts. Additionally, the medical/surgical RN
      staff successfully placed 85% of the medical/surgical PIVs. As a result of this
      study, the standard of practice is now defined as no greater than four attempts
      at insertion by RN staff. Future data should be collected in order to
      substantiate a defined standard for PIV placement.

PMID- 14651306
TI  - Peripherally inserted central catheters (PICCs) in the CF population: one
      center's experience.
AB  - Cystic fibrosis (CF) is a common fatal genetic disorder characterized by chronic
      pulmonary infections, some of which require intravenous (i.v.) antibiotics.
      Peripherally inserted central catheters (PICCs) have proven to be an effective
      means of i.v. delivery in a variety of populations. An evaluation of the
      effectiveness of the use of PICCs for patients at a CF center in New England was
      conducted over a 25-consecutive month period. During this time, 61 PICCs were
      placed in 32 patients with CF requiring i.v. antibiotics. The catheters were in
      place for a median of 15 days (range 1-155 days). The total number of catheter
      days in this series was 1,139. Although no serious complications were
      encountered, minor complications or technical problems occurred in 18 (29.5%) of
      the 61 catheters. Complications included external breaks in the catheters,
      shoulder pain, phlebitis, catheter occlusion, accidental dislodgement, local
      irritation at the insertion site, and yeast infection at the insertion site. No
      long-term sequelae resulted, and the rate of i.v. antibiotic completion with this
      mode of i.v. access was high. As a result of the evaluation, PICC access remains
      the standard of care at this institution for patients with CF requiring i.v.
      antibiotics for pulmonary exacerbations.

PMID- 14651307
TI  - Quality of life for adolescents with type 1 diabetes: parental and youth
      perspectives.
AB  - PURPOSE: This descriptive correlational study explored quality of life for
      adolescents with type 1 diabetes versus healthy adolescents, and possible
      influences of age, gender, race, and metabolic control on quality of life and
      health perception of the adolescents with diabetes. SAMPLE: Sixty-nine
      adolescents with type 1 diabetes treated at a pediatric diabetes center of a
      children's medical center in the Mid-South versus 75 healthy adolescents and
      their respective parents. METHODS: Data were collected using the Diabetes Quality
      of Life Instrument for Youth, the Self-Perception Profile for Adolescents, the
      Children's Behavior Checklist (Competence Scales), and the Functional Status II.
      Chart data included the duration of diabetes, insulin dosage, most recent
      hemoglobin A1c, and average hemoglobin A1c over the past year. RESULTS: Teens
      with diabetes expressed lower life satisfaction and health perception than
      controls; females with diabetes had lower life satisfaction than their male
      counterparts.

PMID- 14651308
TI  - Pediatric management problems. HIV.

PMID- 14651309
TI  - Life-threatening fall.

PMID- 14651310
TI  - Changes in infant sleep problems after a family-centered intervention.
AB  - PURPOSE: To describe a family-centered intervention for sleep disturbed infants
      and its effect on the infants' sleep pattern. METHODS: The sample consisted of 33
      infants (6-23 month of age) hospitalized because of sleep problems in The City
      Hospital in Reykjavik, Iceland, and 33 mothers and 30 fathers. Infants' sleep
      patterns were assessed by a 1-week diary and by interviews with parents before
      hospital admission, 1 week and 2 months after discharge. The intervention was
      based on correction of day-sleep rhythm, support of self-comforting capabilities
      of the infant, and education of parents in regard to the infants' characteristics
      and developmental status. Changes in day naps and infant irritability over
      daytime also improved significantly. FINDINGS: Night sleep improved significantly
      1 week after discharge and even more so 2 months later. CONCLUSIONS: Offering a
      family-centered intervention improves infants' sleep patterns up to 2 months
      after discharge.

PMID- 14651311
TI  - Alternating acetaminophen and ibuprofen in the febrile child: examination of the
      evidence regarding efficacy and safety.

PMID- 14651312
TI  - Lactation suppression: forgotten aspect of care for the mother of a dying child.

PMID- 14651314
TI  - Knights Against Tobacco: teens lead the charge to prevent tobacco use among
      adolescents.

PMID- 14651315
TI  - Get involved! Join a pediatric nursing association just right for you.

PMID- 14651316
TI  - Honor Society of Nursing recognizes nurse researcher. Kathryn Barnard.

PMID- 14651317
TI  - Movements in art: from Rosso to Riley.

PMID- 14651318
TI  - Gaze stability of observers watching Op Art pictures.
AB  - It has been the matter of some debate why we can experience vivid dynamic
      illusions when looking at static pictures composed from simple black and white
      patterns. The impression of illusory motion is particularly strong when viewing
      some of the works of 'Op Artists, such as Bridget Riley's painting Fall.
      Explanations of the illusory motion have ranged from retinal to cortical
      mechanisms, and an important role has been attributed to eye movements. To assess
      the possible contribution of eye movements to the illusory-motion percept we
      studied the strength of the illusion under different viewing conditions, and
      analysed the gaze stability of observers viewing the Riley painting and control
      patterns that do not produce the illusion. Whereas the illusion was reduced, but
      not abolished, when watching the painting through a pinhole, which reduces the
      effects of accommodation, it was not perceived in flash afterimages, suggesting
      an important role for eye movements in generating the illusion for this image.
      Recordings of eye movements revealed an abundance of small involuntary saccades
      when looking at the Riley pattern, despite the fact that gaze was kept within the
      dedicated fixation region. The frequency and particular characteristics of these
      rapid eye movements can vary considerably between different observers, but,
      although there was a tendency for gaze stability to deteriorate while viewing a
      Riley painting, there was no significant difference in saccade frequency between
      the stimulus and control patterns. Theoretical considerations indicate that such
      small image displacements can generate patterns of motion signals in a motion
      detector network, which may serve as a simple and sufficient, but not necessarily
      exclusive, explanation for the illusion. Why such image displacements lead to
      perceptual results with a group of Op Art and similar patterns, but remain
      invisible for other stimuli, is discussed.

PMID- 14651319
TI  - "A moment's monument": the central vision of Italian sculptor Medardo Rosso (1858
      1928).
AB  - One of the basic limitations on visual perception is that it is impossible, in
      any given moment, to see the world sharply and full of colors beyond the central
      area of the visual field. This fact was popularized and brought to the attention
      of artists in the nineteenth century. To accurately represent the 'impression',
      or vision of a single glance, an artistic work should contain only a central area
      in focus surrounded by a progressively greater blur. The work of the Italian
      sculptor Medardo Rosso (1858-1928) may be the first artistic representation of
      differences in central and peripheral acuity. Despite using the medium of
      sculpture, typically three-dimensional, Rosso conceived of his art as two
      dimensional because in a given moment it is possible to view a scene from only
      one viewpoint. The analysis of Rosso's photographs of his own sculptures
      emphasizes the areas of detail and relative blur, allowing a reconstruction of
      his point de vue unique--where the observer should stand when viewing that
      specific sculpture. We argue that the role of central and peripheral vision in
      subjective perception is critical to understanding the work of Rosso, aptly
      defined by critics as monument d'un instant.

PMID- 14651320
TI  - Haptics and projection: drawings by Tracy, a blind adult.
AB  - Outline drawings in a raised form were made by a blind woman, Tracy, who has been
      blind from very early in life. Highly practiced in drawing, she reports she is
      largely self-taught. To invoke matters of projection, she was asked to represent
      an object with faces slanting away from the observer, a fixed array from
      different vantage points, and sets of objects in depth. In particular, she drew a
      cube balanced on a vertex, three objects from different vantage points, receding
      rows of glasses, and a house. Her drawings included features of parallel and
      polar projection. Her use of these features may reflect an appreciation of
      direction from a vantage point, which observers deal with via haptics in everyday
      tasks. Tracy may have advanced drawing-development skills common to the blind and
      the sighted.

PMID- 14651321
TI  - Visually perceived eye level with reversible pitch stimuli: implications for the
      great circle and implicit surface models.
AB  - Visually perceived eye level (VPEL) and perceived pitch were measured while
      subjects viewed two sets of stimuli that were either upright or pitched top
      toward or top-away from them. The first set of stimuli, a pair of vertical lines
      viewed at various angles of pitch, caused systematic changes in perceived pitch
      and upward and downward VPEL shifts for the top-toward and top-away pitches,
      respectively. Neither the perceived pitch nor the VPEL measures with these
      stimuli differed between monocular and binocular viewing. The second set of
      stimuli was constructed so that, when viewed at the appropriate pitch angle, the
      projected orientations of the lines in the retinal image of each stimulus were
      similar to those generated by a pair of vertical lines pitched by a lesser amount
      in the opposite direction. When viewed monocularly, these stimuli appeared
      pitched in the direction opposite their physical pitch, yet produced VPEL shifts
      consistent with the direction of their physical pitch. These results clearly
      demonstrate a dissociation between perceived pitch and VPEL. The same stimuli,
      when viewed binocularly, appeared pitched in the direction of their physical
      pitch and caused VPEL shifts indistinguishable from those obtained monocularly.
      The retinal image orientations of these stimuli, however, corresponded to those
      of vertical line stimuli pitched in the opposite direction. This finding is
      therefore consistent with the hypothesis that VPEL and perceived pitch are
      processed independently, but inconsistent with the specific version of this
      hypothesis which states that differences in VPEL are determined solely on the
      basis of the orientation of lines in the retinal image.

PMID- 14651322
TI  - Sex, beauty, and the relative luminance of facial features.
AB  - It has been suggested that the consistent luminance difference between the darker
      regions of the eyes and mouth and the lighter regions that surround them forms a
      pattern unique to faces. One of the more consistent uses of cosmetics to make the
      female face more attractive is to darken the eyes and mouth relative to the
      surrounding skin. The hypothesis that the size of the luminance difference
      between the eyes and mouth and the rest of the face affects the attractiveness of
      male and female faces differently was tested in four experiments in which
      attractiveness ratings were obtained for images of faces in which the luminance
      difference between the eyes and mouth and the rest of the face had been
      manipulated. Female faces were found to be more attractive when this luminance
      difference was increased than when it was decreased, and the opposite was found
      for male faces. An interpretation consistent with these results is that the
      luminance difference between the eyes and mouth and the rest of the face is
      naturally greater in women than men. In this case increasing or decreasing the
      luminance difference will make a face more feminine or masculine, respectively,
      and hence, more or less attractive depending on the sex of the face. Implications
      for the causes of cosmetics usage are discussed.

PMID- 14651323
TI  - Pulling faces: an investigation of the face-distortion aftereffect.
AB  - After adaptation to a face distorted to look unnaturally thin or fat, a normal
      face appears distorted in the opposite direction (Webster and MacLin 1999
      Psychonomic Bulletin & Review 6 647-653). When the adapting face is oriented 45
      degrees from vertically upright and the test face 45 degrees in the opposite
      direction, the axis of perceived distortion changes with the orientation of the
      face. The magnitude of this aftereffect shows a reduction of approximately 40%
      from that found when both adapting and test faces are tilted identically. This
      finding suggests that to a large degree the aftereffect is mediated not by low
      level retinotopic (image-based) visual mechanisms but at a higher level of object
      based processing. Aftereffects of a similar magnitude are obtained when adapting
      and test images are both either upright or inverted, or for an upright adapter
      and an inverted test; but aftereffects are smaller when the adapter is inverted
      and the test upright. This pattern of results suggests that the face-distortion
      aftereffect is mediated by object-processing mechanisms including, but not
      restricted to, configurational face-processing mechanisms.

PMID- 14651324
TI  - An encoding advantage for own-race versus other-race faces.
AB  - Studies have shown that individuals are better able to recognise the faces of
      people from their own race than the faces of people from other races. Although
      the so-called own-race effect has been generally regarded as an advantage in
      recognition memory, differences in the processing of the own-race versus other
      race faces might also be found at the earlier stages of perceptual encoding. In
      this study, the perceptual basis of the own-race effect was investigated by
      generating a continuum of images by morphing an East Asian parent face with a
      Caucasian parent face. In a same/different discrimination task, East Asian and
      Caucasian participants judged whether the morph faces were physically identical
      to, or different from, their parent faces. The results revealed a significant
      race-of-participant by race-of-face interaction such that East Asian participants
      were better able to discriminate East Asian faces, whereas Caucasian participants
      were better able to discriminate Caucasian faces. These results indicate that an
      own-race advantage occurs at the encoding stage of face processing.

PMID- 14651325
TI  - Do expertise and the degree of perception-action coupling affect natural
      anticipatory performance?
AB  - Two experiments using a temporal occlusion paradigm (the first with expert and
      novice participants and the second with participants of intermediate skill) were
      conducted to examine the capability of tennis players to predict the direction of
      an opponent's service in situ. In both experiments two different response
      conditions, reflecting differing degrees of perception-action coupling, were
      employed. In a coupled condition players were required to make a movement-based
      response identical to that which they would use to hit a return of service in a
      game situation, whereas in an uncoupled condition a verbal prediction of service
      direction was required. Experiment 1 provided clear evidence of superior
      prediction accuracy under the coupled response condition when ball flight was
      available, plus some limited evidence to suggest that superior prediction
      accuracy under uncoupled response conditions might hold true if only advance (pre
      contact) information was available. Experiment 2 showed the former finding to be
      a robust one, but was unable to reveal any support for the latter. Experiment 1
      also revealed that expert superiority is more apparent for predictions made under
      natural (coupled) than uncoupled response-mode conditions. Collectively, these
      findings suggest that different perceptual processes may be in operation in
      anticipatory tasks which depend on skill level, the type of information
      presented, and degree of perception-action coupling inherent in the task
      requirements.

PMID- 14651326
TI  - First-order and second-order spectral 'motion' mechanisms in the human auditory
      system.
AB  - Light energy displaced along the retinal photoreceptor array leads to a
      perception of visual motion. In audition, displacement of mechanical energy along
      the cochlear hair cell array is conceptually similar but leads to a perception of
      'movement' in frequency space (spectral motion)--a rising or falling pitch. In
      vision there are other types of stimuli that also evoke a percept of motion but
      do not involve a displacement of energy across the photoreceptors (second-order
      stimuli). In this study, we used psychophysical methods to determine if such
      second-order stimuli also exist in audition, and if the resulting percept would
      rival that of first-order spectral motion. First-order auditory stimuli consisted
      of a frequency sweep of sixteen non-harmonic tones between 297 and 12123 Hz.
      Second-order stimuli consisted of the same tones, but with a random subset turned
      on at the beginning of a trial. During the trial, each tone in sequence randomly
      changed state (ON-to-OFF, or OFF-to-ON). Thus, state transitions created a
      'sweep' having no net energy displacement correlated to the sweep direction. At
      relatively slow sweep speeds, subjects readily identified the sweep direction for
      both first-order and second-order stimuli, though accuracy decreased for second
      order stimuli as the sweep speed increased. This latter characteristic is also
      true of some second-order visual stimuli. These results suggest a stronger
      parallelism between auditory and visual processing than previously appreciated.

PMID- 14651327
TI  - Golfers may have to overcome a persistent visuospatial illusion.

PMID- 14651328
TI  - Evaluation of human resistin assays with serum from patients with type 2 diabetes
      and different degrees of insulin resistance.
AB  - Resistin is a peptide hormone encoded at the RSTN gene that since its detection
      in mice is considered to be an important link between obesity and insulin
      resistance. However, the study reports and especially the human data are
      contradictory and require further investigation. The purpose of this study was to
      evaluate three commercially available resistin ELISAs with different target
      epitopes (Phoenix, Belmont, CA, USA (PH); Biovendor, Brno, Czech Republic (BV);
      and Immundiagnostik, Bensheim, Germany (ID)) from a laboratory and clinical
      perspective. All three assays successfully passed the standardized technical
      validation procedure, with an inter- and intra-assay variability below 10% and
      15%, respectively. They proved to be different with regard to calibration and
      reference ranges, which may be linked to the different antibody specificities.
      The clinical evaluation was performed with fasting serum samples from 78 patients
      with type 2 diabetes (43 female, 35 male, age (mean +/- SD, range): 67 +/- 10,
      (41-86) years; BMI: 29.2 +/- 4.2 (21.6-41.9) kg/m2). Insulin resistance was
      calculated from the fasting insulin and glucose values by means of the HOMA
      analysis. Intact proinsulin served as comparative laboratory marker for insulin
      resistance. The mean resistin values of patients without insulin resistance were
      slightly higher (PH: 9.5 +/- 2.8 ng/ml; BV: 4.1 +/- 4.0 ng/ml; ID: 3.8 +/- 9.0
      ng/ml) than the mean values of the resistant patients (PH: 9.0 +/- 1.7 ng/ml,
      n.s.; BV: 3.8 +/- 1.3 ng/ml, n.s.; ID: 0.8 +/- 1.0 ng/ml, p<0.05). Intact
      proinsulin levels correlated well with the HOMA score values (r = 0.64, p<0.001).
      No correlation was seen between any of the resistin assays and any of the other
      clinical or laboratory observation parameters collected, such as BMI, age,
      disease duration, triglycerides, LDL, HDL, insulin, glucose, or intact
      proinsulin. In conclusion, the resistin assays showed good technical quality, but
      the diagnostic value remains still unclear. It may, however, be concluded from
      this study that at least in cross-sectional epidemiological investigations,
      fasting human resistin concentrations are not significantly correlating with any
      clinical measure for insulin resistance.

PMID- 14651329
TI  - Laboratory-based diagnosis of brucellosis--a review of the literature. Part II:
      serological tests for brucellosis.
AB  - Brucellosis is a common zoonotic disease transmittable to humans from infected
      animal reservoirs. Malta, Rock, Gibraltar, Cyprus or Mediterranean fever, Bang's
      disease, intermittent typhoid or typho-malarial fever, undulant fever, etc. are
      just various synonyms for brucellosis. Patients suffering from this disease show
      unspecific symptoms, e.g. fever, chills, malaise, arthralgia, headache, tiredness
      and weakness. Human brucellosis may be caused by four of totally six genetically
      and phenotypically closely related Brucella species, i.e. B. melitensis, B.
      abortus, B. suis and B. canis. Although many organ systems may be involved,
      brucellosis is rarely fatal. Therapeutic failure and relapses, chronic courses
      and severe complications like bone and joint involvement, neurobrucellosis and
      endocarditis are characteristic for the disease. A definite diagnosis requires
      the isolation of Brucellae from blood, bone marrow or other tissues. However,
      cultural examinations are time-consuming, hazardous and not sensitive. Thus,
      clinicians often rely on the indirect proof of infection. The detection of high
      or rising titers of specific antibodies in the serum allows a tentative
      diagnosis. A variety of serological tests has been applied, but at least two
      serological tests have to be combined to avoid false negative results. Usually,
      the serum agglutination test is used for a first screening and complement
      fixation or Coombs' test will confirm its results. As Brucella ELISAs are more
      sensitive and specific than other serological tests, they may replace them step
      by step. This review will summarize advantages and disadvantages of the
      serological techniques used in clinical laboratories for indirect verification of
      human brucellosis.

PMID- 14651330
TI  - Autoantibodies to thyroperoxidase (TPOAb) in a large population of euthyroid
      subjects: implications for the definition of TPOAb reference intervals.
AB  - OBJECTIVE: Measurement of autoantibodies against thyroperoxidase (TPOAb) plays an
      important role in the diagnosis of autoimmune thyroid disease. The assessment of
      reference intervals for TPOAb, however, is a controversial issue since elevated
      TPOAb values are sometimes found in subjects without other evidence of thyroid
      disease. METHODS: TPOAb were measured in 1,295 euthyroid individuals using a
      highly sensitive, fully automated chemiluminescence assay (Advantage A-TPO,
      Nichols Institute Diagnostics, CA, USA). The study subjects participated in a
      population study on the prevalence of thyroid disorders in the German federal
      state of Saxony, an area of mild iodine deficiency. RESULTS: TPOAb above the
      detection limit of 0.45 IU/ml were found in 1,277/1,295 euthyroid individuals.
      TPOAb values in the low measurable range below 1.1 IU/ml followed a normal
      distribution, and this was independent of age and sex. When using a cut-off value
      of 1.1 IU/ml, which corresponds to a sensitivity of 79% and a specificity of 95%
      resulting from the receiver-operator characteristic plot for discrimination
      between a main type and other types with a higher mean value of TPOAb, elevated
      TPOAb were found in 14.4% of euthyroid men and in 25.8% of euthyroid women.
      CONCLUSIONS: The results demonstrate for the first time that TPOAb are detectable
      in nearly all euthyroid individuals and that TPOAb values in the low measurable
      range are normally distributed. The distribution of TPOAb values in the low range
      is independent of age and sex. Based on these data, reference intervals for TPOAb
      can be defined that are independent of the population investigated. The clinical
      significance of slightly elevated TPOAb, however, has still to be defined by
      prospective studies.

PMID- 14651331
TI  - Role of lipases, lecithin:cholesterol acyltransferase and cholesteryl ester
      transfer protein in abnormal high density lipoprotein metabolism in insulin
      resistance and type 2 diabetes mellitus.
AB  - Dyslipidaemia, hallmarked by low HDL cholesterol and high plasma triglycerides,
      is a feature of insulin resistance and type 2 diabetes mellitus. These
      lipoprotein abnormalities represent major cardiovascular risk factors in these
      conditions. Among other factors, lipoprotein lipase (LPL), hepatic lipase (HL),
      lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer
      protein (CETP) play an important role in an abnormal HDL metabolism in insulin
      resistance and type 2 diabetes mellitus. LPL hydrolyses lipoprotein
      triglycerides, thus providing lipids for HDL formation. In insulin resistant
      states, a decreased post-heparin plasma LPL activity contributes to a low HDL
      cholesterol, whereas an increased activity of HL reduces HDL particle size by
      hydrolysing its triglycerides and phospholipids. High HL activity coincides with
      low HDL cholesterol. The esterification of free cholesterol by LCAT increases HDL
      particle size. Subsequent CETP action results in transfer of cholesteryl esters
      from HDL towards triglyceride-rich lipoproteins. This cholesteryl ester transfer
      process results in lower HDL cholesterol and indirectly decreases HDL size.
      Plasma cholesterol esterification is unaltered or increased, whereas cholesteryl
      ester transfer is enhanced in type 2 diabetes mellitus, abnormalities which are
      probably related to the degree of hypertriglyceridaemia. It is plausible that a
      low LPL activity contributes to premature atherosclerosis as observed in insulin
      resistance and type 2 diabetes mellitus, but the effects of high HL activity and
      altered plasma cholesterol esterification on atherosclerosis development are
      uncertain. Since the cholesteryl ester transfer process between lipoproteins
      provides a metabolic intermediate between low HDL cholesterol and high plasma
      triglycerides, hypertriglyceridaemia-associated accelerated transfer of
      cholesteryl ester out of HDL may be pathogenetically involved in the development
      of cardiovascular disease in insulin resistance and type 2 diabetes mellitus.

PMID- 14651332
TI  - Cancer and venous thromboembolism: a multidisciplinary approach.
AB  - In this paper, we briefly review the relation between cancer and venous
      thromboembolism (VTE), an association that has been recognized for more than a
      century. In particular we focus on VTE as predictor and prognostic factor for
      cancer and the antineoplastic potential of antithrombotic treatment. Cancer may
      cause disturbances in the haemostatic system by numerous mechanisms that can lead
      to an increased risk of VTE. Patients with known cancer are at increased risk of
      VTE; however, VTE may also be a predictor of subsequent cancer in the years
      afterwards. Furthermore, cancer patients with VTE are more likely to have
      advanced disease and a worse prognosis than cancer patients without a VTE
      episode. These findings may have implications for the clinical care of patients
      with VTE in terms of screening for cancer. However, extensive cancer screening
      programs are not recommended in general for patients with VTE. A wide range of
      antithrombotic drugs including heparin, oral anticoagulants, and platelet
      inhibitors have been examined in order to study the effect on the prevention and
      treatment of various cancers. These efforts have resulted in a considerable
      amount of useful data from animal models and a number of promising reports from
      retrospective analyses and small-scale trials linking antithrombotic treatment
      with an increased survival in cancer patients and even a lower risk of primary
      cancer. However, the clinical implications of these findings must await properly
      designed and conducted randomized clinical trials.

PMID- 14651333
TI  - Circulating levels of osteoclast activating cytokines, interleukin-11 and
      transforming growth factor-beta2, as valuable biomarkers for the assessment of
      bone turnover in postmenopausal osteoporosis.
AB  - The objective of this study was to evaluate the role of osteoclast activating
      cytokines, interleukin-11 (IL-11) and transforming growth factor-beta2 (TGF
      beta2) in the assessment of bone turnover in postmenopausal osteoporosis (PO).
      Eighty postmenopausal osteoporotic women with lumbar spine bone mineral densities
      (BMD) as measured by DEXA that were more than 2.5 SD below the normal mean of
      healthy women (controls), participated in this study. Various therapeutic
      modalities (hormone replacement therapy, HRT, alendronate, calcitonin and 1alpha
      hydroxyvitamin D (alfacalcidol) were administered for 12 months to 4 groups of
      postmenopausal osteoporotic patients. Fasting blood samples and two hour urine
      samples were collected from control subjects and from patients before and after
      treatment. Serum samples were assayed for IL-11, TGF-beta2, osteocalcin (OC) and
      bone alkaline phosphatase (B-ALP), whereas urine samples were assayed for N
      telopeptide for type I collagen (NTX) and deoxypyridinoline (DPyr). The results
      demonstrated a significant increase of both IL-11 and TGF-beta2 in postmenopausal
      osteoporosis. Positive correlations exist between TGF-beta2 or IL-11 and markers
      of bone resorption (NTX and DPyr). Moreover, there was a significant positive
      correlation between TGF-beta2 and IL-11. Therapeutic modalities enhancing bone
      formation and/or with antiresorptive effect revealed a significant decrease in
      markers of bone resorption, formation and osteoclast activating cytokines,
      indicating a decrease in bone turnover. The decrease of IL-11 and TGF-beta2 may
      be attributed to a drug inhibitory effect of these cytokines on enhancing
      osteoblast mediated osteoid degradation. In conclusion, both serum IL-11 and TGF
      beta2 determinations may be considered as biomarkers for the assessment of bone
      turnover and for monitoring antiresorptive therapy in postmenopausal
      osteoporosis.

PMID- 14651334
TI  - Fluorimetric analysis of hydrogen peroxide with automated measurement.
AB  - In the pathophysiology of chronic obstructive pulmonary disease (COPD) oxidative
      stress plays an important role, which can be determined by measuring hydrogen
      peroxide. Hydrogen peroxide can be measured fluorimetrically in exhaled breath
      condensate (EBC), however, not standardized. The objective of this study was to
      investigate the sensitivity and reproducibility of measuring the hydrogen
      peroxide concentration in EBC of COPD patients using an automated flow injection
      device with varying flow rates and measurements. METHODS: 10 microl p
      hydroxyphenylacetic acid (1.0 mmol/l) and 10 microl horseradish peroxidase (15
      mU/l) were manually added to several hydrogen peroxide containing solutions and
      EBC of patients suffering from COPD. The fluorescence of the reaction product was
      measured with an automated sampler, flow injection and scanning fluorescence
      detector, excitation wave 295 nm, emission wave 405 nm, at different flow rates.
      The degree of fluorescence was expressed as either the area under the curve or
      the peak value. RESULTS: A flow rate of 1 ml/min gave the best results. There
      were no significant differences in calibration curves or detection limits using
      area under the curve or peak value (respectively 0.007 and 0.005 micromol/l)
      (flow rate 1.0 ml/min). The mean volume of EBC was 2.8 ml, the mean hydrogen
      peroxide concentration in the patient group was 0.2 micromol/l and the standard
      deviation of duplication 0.009 micromol/. CONCLUSIONS: The low detection limit
      may be explained by using flow injection, because it measures the fluorescence
      over a period of time. It is important to choose an appropriate flow rate. There
      is no difference in the detection limit between measuring the fluorescence as
      area under the curve or as peak value.

PMID- 14651335
TI  - Polymorphisms in the TAFI gene and the risk of venous thrombosis.
AB  - Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described
      inhibitor of fibrinolysis. The aim of this study was to estimate the risk of deep
      venous thrombosis (DVT) caused by the polymorphisms in the TAFI gene in relation
      to polymorphisms of the other fibrinolytic variables such as PAI-844A>G and t-PA
      7,351C>T. This study includes 130 patients with DVT and 130 age- and sex-matched
      healthy controls. Our results showed no association of the investigated "TAFI
      increasing" alleles TAFI 505A (Thr147) and TAFI+1542C with the risk of venous
      thrombosis. However the adjustment for age, sex, factor V Leiden, PAI-844A allele
      and t-PA-7,351T allele indicates a tendency to a moderately increased thrombotic
      risk of TAFI+1542GG carriers (low TAFI level).

PMID- 14651336
TI  - The influence of renal function on NT-proBNP levels in various disease groups.

PMID- 14651337
TI  - Standardization of two immunological HbA1c routine assays according to the new
      IFCC reference method.
AB  - The measurement of HbA1c is meanwhile well established as the most important
      parameter in clinical chemistry for monitoring the long term metabolic control of
      diabetic patients. However, the comparability of HbA1c values obtained by
      different methods in different laboratories and different countries is limited
      since there was no internationally agreed reference method available.
      Additionally the % HbA1c values, based on the most common DCCT values are too
      high due to well known non specificity of the DCCT standardization protocol.
      Recently a new reference method for the determination of HbA1c was developed and
      has been approved by the IFCC as the future basis for the worldwide
      standardization of HbA1c routine assays. The two routine methods from Roche
      Diagnostics (both based on the immunoturbidimetric determination of the stable
      glucose adduct to the N-terminal group of the hemoglobin beta chain, Roche
      Hitachi/Tina-quant [a] and COBAS INTEGRA) are directly standardized against this
      new reference method. Both routine methods are based on a two step approach: in a
      first step the total Hb is quantified by a colorimetric method and in a second
      step the stable glucose adduct to the N-terminal group of the hemoglobin beta
      chain is quantified by immunoturbidity (HbA1c mass). Consequently, first the
      standardization of the total Hb assay was reconfirmed by method comparisons
      against the cyanomethemoglobin reference method. Second, the standardization of
      the HbA1c mass was done by running method comparisons against the new IFCC
      reference method. The resulting new calibrator values for HbA1c [mass] and total
      Hb [mass] allow a direct estimation of % HbA1c according to IFCC just by
      calculating the HbA1c [mass]/total Hb [mass] ratio. Good linear correlations were
      obtained when comparing the routine methods against the new IFCC reference,
      indicating the high specificity of these immunological approaches. The following
      correlations are obtained: Hitachi / Tina-quant [a] (Y) versus IFCC reference
      method (X): Y = -0.031 + 1.009 x X; r = 0.995. COBAS INTEGRA (Y) versus IFCC
      reference method (X): Y = -0.156 + 1.006 x X; r = 0.997. Hitachi / Tina-quant [a]
      (Y) versus Integra (X); (both standardized according to IFCC): Y = 0.057 + 1.003
      x X; r = 0.997. The HbA1c values obtained with this new IFCC standardization are
      significantly lower than the well known DCCT values. Due to the specificity of
      the immunological approach which is very close to the analyte as defined by the
      IFCC reference method, no further corrections of the obtained % HbA1c values are
      necessary. A slope/intercept correction formula is derived which allows the
      transformation of IFCC values into the DCCT numbers if requested.

PMID- 14651338
TI  - Nodulation of Mimosa spp. by the beta-proteobacterium Ralstonia taiwanensis.
AB  - Several beta-proteobacteria have been isolated from legume root nodules and some
      of these are thought to be capable of nodulating and fixing N2. However, in no
      case has there been detailed studies confirming that they are the active
      symbionts. Here, Ralstonia taiwanensis LMG19424, which was originally isolated
      from Mimosa pudica nodules, was transformed to carry the green fluorescent
      protein (gfp) reporter gene before being used to inoculate axenically-grown
      seedlings of M. pudica and M. diplotricha. Plants were harvested at various
      intervals for 56 days after inoculation, then examined for evidence of infection
      and nodule formation. Nodulation of both Mimosa spp. was abundant, and acetylene
      reduction assays confirmed that nodules had nitrogenase activity. Confocal laser
      scanning microscopy (CLSM) showed that fresh M. pudica nodules with nitrogenase
      activity had infected cells containing bacteroids expressing gfp. In parallel,
      fixed and embedded nodules from both Mimosa spp. were sectioned for light and
      electron microscopy, followed by immunogold labeling with antibodies raised
      against gfp and nitrogenase Fe (nifH) protein. Significant immunolabeling with
      these antibodies confirmed that R. taiwanensis LMG19424 is an effective N2-fixing
      symbiont of Mimosa spp. Both species were infected via root hairs and, in all
      respects, the nodule ontogeny and development was similar to that described for
      other mimosoid legumes. The nodules were indeterminate with a persistent
      meristem, an invasion zone containing host cells being invaded via prominent
      infection threads, and an N2-fixing zone with infected cells containing membrane
      bound symbiosomes.

PMID- 14651339
TI  - Induction of the Hahsp17.7G4 promoter by root-knot nematodes: involvement of heat
      shock elements in promoter activity in giant cells.
AB  - Root-knot nematodes feed from specialized giant cells induced in the plants that
      they parasitize. We found that the promoter of the Hahsp17.7G4 gene, which
      encodes a small heat-shock protein involved in embryogenesis and stress
      responses, directed GUS expression in tobacco galls induced by the root-knot
      nematode Meloidogyne incognita. In roots containing a GUS reporter fusion to the
      Hahsp17.7G4 promoter, 10% of the galls stained for GUS expression 1 to 3 days
      after infection and the fraction stained increased to 60 to 80% 17 to 20 days
      after infection. A DNA fragment from -83 to +163, which contains heat-shock
      element (HSE) core sequences, is sufficient to support a promoter activity
      largely restricted to giant cells within the galls. Two-point mutations in HSE
      cores, previously reported to abolish the heat-shock response and to strongly
      reduce the embryogenesis response of the same promoter, did not reduce expression
      in giant cells. This suggests a distinct regulation of the promoter by nematodes.
      However, additional point mutations located at positions crucial for binding of
      heat-shock transcription factors (HSFs) caused a severe decrease in the nematode
      response. These results demonstrate that HSEs are involved in the promoter
      activation in giant cells and suggest that HSFs may mediate this response.

PMID- 14651340
TI  - The glucocorticoid-inducible GVG system causes severe growth defects in both root
      and shoot of the model legume Lotus japonicus.
AB  - During the past decade, the legume Lotus japonicus has emerged as an important
      model system for study of symbiotic nitrogen fixation. Controlled expression of
      genes involved in symbiosis from an inducible promoter at specific time points
      would be a valuable tool for investigating gene function in L. japonicus. We have
      attempted to study the function of the putative transcription factors LjNDX and
      LjCPP1 by expression from the GVG inducible system. This study showed that the
      GVG system itself causes growth disturbances in L. japonicus. Shoot internode
      elongation and root pericycle cell division are affected when the chimeric GVG
      transcription factor is activated. We suggest that deficient auxin signaling
      could cause the phenotype observed and conclude that the GVG inducible system is
      not well suited for use in the model legume L. japonicus.

PMID- 14651341
TI  - A set of genes differentially expressed between avirulent and virulent
      Meloidogyne incognita near-isogenic lines encode secreted proteins.
AB  - A cDNA-amplification fragment length polymorphism (AFLP)-based strategy has been
      used to identify genes differentially expressed between two pairs of near
      isogenic lines (NIL) of the root-knot nematode Meloidogyne incognita either
      avirulent or virulent against the tomato Mi resistance gene. Gene expression
      profiles from infective second-stage juveniles (J2) were compared, and 22 of the
      24,025 transcript-derived fragments (TDF) generated proved to be differential,
      i.e., present in both avirulent NIL and absent in both virulent NIL. Fourteen of
      the TDF sequences did not show any significant similarity to known proteins,
      while eight matched reported sequences from nematodes and other invertebrates.
      The differential expression of nine genes was confirmed by reverse transcription
      polymerase chain reaction (RT-PCR) experiments. In situ hybridization conducted
      with five of the sequences showed that two were specifically expressed in the
      intestinal cells (HM10 and PM1), one in the subventral esophageal glands (HM1),
      and two in the dorsal esophageal gland of J2 (HM7 and HM12). Analysis of full
      length cDNA sequences revealed the presence of a signal peptide for HM1, HM10,
      and HM12, indicating that the encoded proteins are putatively secreted. Since
      secreted products in general and esophageal gland secretions in particular are
      thought to be among the main M. incognita pathogenicity factors, this result
      suggests a possible dual role for some of the genes encoding such secretions,
      i.e., they could be involved in both pathogenicity and virulence or avirulence of
      these biotrophic parasites.

PMID- 14651342
TI  - Three genes encoding for putative methyl- and acetyltransferases map adjacent to
      the wzm and wzt genes and are essential for O-antigen biosynthesis in Rhizobium
      etli CE3.
AB  - The elucidation of the structure of the O-antigen of Rhizobium etli CE3 predicts
      that the R. etli CE3 genome must contain genes encoding acetyl- and
      methyltransferases to confer the corresponding modifications to the O-antigen. We
      identified three open reading frames (ORFs) upstream of wzm, encoding the
      membrane component of the O-antigen transporter and located in the lps alpha
      region of R. etli CE3. The ORFs encode two putative acetyltransferases with
      similarity to the CysE-LacA-LpxA-NodL family of acetyltransferases and one
      putative methyltransferase with sequence motifs common to a wide range of S
      adenosyl-L-methionine-dependent methyltransferases. Mutational analysis of the
      ORFs encoding the putative acetyltransferases and methyltransferase revealed that
      the acetyl and methyl decorations mediated by these specific enzymes are
      essential for O-antigen synthesis. Composition analysis and high performance
      anion exchange chromatography analysis of the lipopolysaccharides (LPSs) of the
      mutants show that all of these LPSs contain an intact core region and lack the O
      antigen polysaccharide. The possible role of these transferases in the decoration
      of the O-antigen of R. etli is discussed.

PMID- 14651343
TI  - Nitric oxide-mediated transcriptional changes in Arabidopsis thaliana.
AB  - Nitric oxide (NO) is an essential regulatory molecule in several developmental
      processes and in the stress response in both animal and plant systems.
      Furthermore, key features of plant resistance to pathogens have been shown to
      depend on NO production, e.g., defense gene expression and the activation of a
      hypersensitive reaction (HR) in synergy with reactive oxygen species (ROS). Due
      to the many possible mechanisms of NO action, a clear picture of its involvement
      in plant resistance to pathogens is far from being achieved. Transcriptional
      changes related to NO action are likely to play a significant role in resistance
      and cell death. We investigated the changes in the expression profiles of
      Arabidopsis thaliana following infiltration with the NO donor sodium
      nitroprusside, by cDNA-amplification fragment length polymorphism (AFLP)
      transcript profiling. Altered expression patterns were detected for 120 of the
      approximately 2,500 cDNAs examined. Sequence analysis revealed homologies with
      genes involved in signal transduction, disease resistance and stress response,
      photosynthesis, cellular transport, and basic metabolism or with sequences coding
      for unknown proteins. Comparison of the expression profiles with data from public
      microarray sources revealed that many of the identified genes modulated by NO
      were previously reported to be modulated in disease-related experiments.

PMID- 14651344
TI  - GacA, the response regulator of a two-component system, acts as a master
      regulator in Pseudomonas syringae pv. tomato DC3000 by controlling regulatory
      RNA, transcriptional activators, and alternate sigma factors.
AB  - Concerted investigations of factors affecting host-pathogen interactions are now
      possible with the model plant Arabidopsis thaliana and its model pathogen
      Pseudomonas syringae pv. tomato DC3000, as their whole genome sequences have
      become available. As a prelude to analysis of the regulatory genes and their
      targets, we have focused on GacA, the response regulator of a two-component
      system. The DC3000 gene was cloned by testing for the reversal of phenotypes of
      an Erwinia GacA- mutant. A GacA- mutant of DC3000 constructed by marker exchange
      produces much-reduced levels of transcripts of three alternate sigma factors:
      HrpL, required for the production of effector proteins and their translocation
      via the type III secretion system; RpoS, required for stress responses and
      secondary metabolite production; and RpoN, required for an assortment of
      metabolic processes and expression of hrpL. GacA deficiency also reduces the
      expression of hrpR and hrpS, which specify enhancer-binding proteins of the NtrC
      family required for hrpL transcription; ahlI and ahlR, the genes for quorum
      sensing signal; salA, a regulatory gene known to control virulence; CorS, a
      sensor kinase; CorR, the cognate response regulator that controls coronatine
      biosynthetic genes; and rsmB and rsmZ, which specify untranslatable regulatory
      RNA species. gacA expression itself is regulated by environmental conditions in
      DC3000, since transcript levels are affected by growth phase and media
      composition. The observations that high levels of gacA RNA occur in the hrp
      inducing medium and GacA deficiency reduces the levels of rpoS expression
      implicate an important role of GacA in stress responses of DC3000. Consistent
      with the effects on hrpL expression, the GacA- mutant produces lower levels of
      transcripts of avr, hrp, and hop genes controlled by HrpL. In addition, GacA
      deficiency results in reduced levels of transcripts of several HrpL-independent
      genes. As would be expected, these effects on gene expression cause drastic
      changes in bacterial behavior: virulence towards A. thaliana and tomato;
      multiplication in planta; efficiency of the induction of the hypersensitive
      reaction (HR); production of pigment and N-acyl-homoserine lactone (AHL), the
      presumed quorum-sensing signal; and swarming motility. Our findings establish
      that GacA, located at the top in a regulatory cascade in DC3000, functions as a
      central regulator by controlling an assortment of transcriptional and
      posttranscriptional factors.

PMID- 14651345
TI  - Laminarin elicits defense responses in grapevine and induces protection against
      Botrytis cinerea and Plasmopara viticola.
AB  - Grapevine (Vitis vinifera L.) is susceptible to many pathogens, such as Botrytis
      cinerea, Plasmopara viticola, Uncinula necator, and Eutypa lata. Phytochemicals
      are used intensively in vineyards to limit pathogen infections, but the
      appearance of pesticide-resistant pathogen strains and a desire to protect the
      environment require that alternative strategies be found. In the present study,
      the beta-1,3-glucan laminarin derived from the brown algae Laminaria digitata was
      shown both to be an efficient elicitor of defense responses in grapevine cells
      and plants and to effectively reduce B. cinerea and P. viticola development on
      infected grapevine plants. Defense reactions elicited by laminarin in grapevine
      cells include calcium influx, alkalinization of the extracellular medium, an
      oxidative burst, activation of two mitogen-activated protein kinases, expression
      of 10 defense-related genes with different kinetics and intensities, increases in
      chitinase and beta-1,3-glucanase activities, and the production of two
      phytoalexins (resveratrol and epsilon-viniferin). Several of these effects were
      checked and confirmed in whole plants. Laminarin did not induce cell death. When
      applied to grapevine plants, laminarin reduced infection by B. cinerea and P.
      viticola by approximately 55 and 75%, respectively. Our data describing a large
      set of defense reactions in grapevine indicate that the activation of defense
      responses using elicitors could be a valuable strategy to protect plants against
      pathogens.

PMID- 14651346
TI  - The cre1 and cre3 nematode resistance genes are located at homeologous loci in
      the wheat genome.
AB  - Differential responses in host-nematode pathotype interactions occur in wheat
      lines carrying different cereal cyst nematode resistance (Cre) genes. Cre1,
      located on chromosome 2B, confers resistance to most European nematodes and the
      sole Australian pathotype, while Cre3, present on chromosome 2D, is highly
      resistant to the Australian pathotype and susceptible to a number of European
      pathotypes. Genes encoding nucleotide binding site-leucine rich repeat (NBS-LRR)
      proteins that cosegregate with the Cre3 locus cross hybridize to homologues whose
      restriction fragment length polymorphism (RFLP) patterns distinguish near
      isogenic Cre1 nematode-resistant wheat lines. Genetic mapping showed that the NBS
      LRR gene members that distinguished the Cre1 near-isogenic lines were located on
      chromosome 2BL at a locus, designated Xcsl107, that cosegregates with the Cre1
      locus. A haplotype of NBS-LRR genes from the Xcsl107 locus provides a diagnostic
      marker for the presence of Cre1 nematode resistance in a wide collection of wheat
      lines and segregating families. Genetic analysis of NBS-LRR haplotypes that
      cosegregate with Cre1 and Cre3 resistance, together with flanking cDNA markers
      and other markers from homoeologous group 2 chromosomes, revealed a conserved
      gene order that suggests Cre1 and Cre3 are homeoloci.

PMID- 14651347
TI  - Depletion of the photosystem II core complex in mature tobacco leaves infected by
      the flavum strain of tobacco mosaic virus.
AB  - The flavum strain of Tobacco mosaic virus (TMV) differs from the wild-type (wt)
      virus by causing strong yellow and green mosaic in the systemically infected
      developing leaves, yellowing in the fully expanded leaves, and distinct
      malformations of chloroplasts in both types of infected tissues. Analysis of the
      thylakoid proteins of flavum strain-infected tobacco leaves indicated that the
      chlorosis in mature leaves was accompanied by depletion of the entire photosystem
      II (PSII) core complexes and the 33-kDa protein of the oxygen evolving complex.
      The only change observed in the thylakoid proteins of the corresponding wt TMV
      infected leaves was a slight reduction of the alpha and beta subunits of the ATP
      synthase complex. The coat proteins of different yellowing strains of TMV are
      known to effectively accumulate inside chloroplasts, but in this work, the viral
      movement protein also was detected in association with the thylakoid membranes of
      flavum strain-infected leaves. The mRNAs of different enzymes involved in the
      chlorophyll biosynthesis pathway were not reduced in the mature chlorotic leaves.
      These results suggest that the chlorosis was not caused by reduction of pigment
      biosynthesis, but rather, by reduction of specific proteins of the PSII core
      complexes and by consequent break-down of the pigments.

PMID- 14651348
TI  - Oxidative burst elicited by Bacillus mycoides isolate Bac J, a biological control
      agent, occurs independently of hypersensitive cell death in sugar beet.
AB  - Response of sugar beet cultivars C40 and USH11 to syringe infiltration of live
      and dead Bacillus mycoides isolate Bac J, a biological control agent, and
      virulent and avirulent isolates of Erwinia carotovora pv. betavasculorum was
      measured by monitoring systemic acquired resistance control of Cercospora
      beticola, specific activity of chitinase and beta-glucanase, the oxidative burst,
      and hypersensitive cell death at the infiltration site. Priming sugar beet with
      B. mycoides Bac J (1 x 10(8) cells/ml) and avirulent isolates of E. carotovora
      pv. betavasculorum (1 x 10(6) cells/ml) reduced C. beticola symptoms by nearly
      70% on distal, untreated leaves. Systemic resistance responses elicited by live
      B. mycoides Bac J and avirulent E. carotovora pv. betavasculorum isolates,
      measured by assays for chitinase and beta-glucanase, were statistically
      equivalent, and biphasic hydrogen peroxide production was observed. Although
      similar in timing, the second hydrogen peroxide burst was twofold lower for B.
      mycoides Bac J than for avirulent E. carotovora pv. betavasculorum.
      Hypersensitive cell death was elicited by avirulent E. carotovora pv.
      betavasculorum but not B. mycoides Bac J. An oxidative burst was elicited by
      spray-applied B. mycoides Bac J under both light and green light conditions,
      indicating that the signal produced by B. mycoides Bac J was not reliant on the
      stomata for entry into sugar beet. A working model for signal delivery and
      systemic resistance induction by B. mycoides Bac J in sugar beet is proposed.

PMID- 14651349
TI  - Differentiation of prostate cancer and benign prostatic hyperplasia: the clinical
      value of 201Tl SPECT--a pilot study.
AB  - PURPOSE: Thallium-201 (201Tl) is a recognized tumor-imaging agent; however, the
      usefulness of 201Tl in prostate cancer has not been studied. The purpose of this
      preliminary study was to evaluate the efficacy of 201Tl single-photon emission
      computed tomography (SPECT) imaging for differentiating prostate cancer from
      benign prostatic hyperplasia (BPH). METHODS: 201Tl pelvic SPECT was performed in
      10 patients (aged 64-78 years) with biopsy-proven BPH before transurethral
      resection of the prostate and 15 patients (aged 65-81 years) with biopsy-proven
      prostate cancer prior to any therapeutic modality or invasive surgical procedures
      for treatment of their prostate cancer. RESULTS: From the 15 patients with
      prostate cancer, 201Tl pelvic SPECT detected prostate cancer in 13 (86.7%) but
      not in 2 (13.3%) patients with Gleason scores of 5 (2 + 3). In contrast, all 10
      patients with BPH (100.0%) had negative results of 201Tl pelvic SPECT.
      CONCLUSION: Our study showed that 201Tl pelvic SPECT scan is very helpful in
      distinguishing between prostate cancer and BPH.

PMID- 14651350
TI  - Evaluation of the number of SPECT projections in the ordered subsets-expectation
      maximization image reconstruction method.
AB  - Filtered back projection (FBP) method, maximum likelihood-expectation
      maximization(ML-EM) method, and ordered subsets-expectation maximization (OS-EM)
      method are currently used for reconstruction of SPECT images in clinical studies.
      In the ML-EM method, images of good quality can be reconstructed even with a
      small sampling number of projection data, when compared with FBP. Shorter
      acquisition time and less radionuclide dose are preferable in the clinical
      setting if image quality is the same. In this study, we attempted to find optimal
      conditions for reconstruction of OS-EM images with commonly used sampling numbers
      of 30, 60 and 120 (step angles: 12 degrees, 6 degrees, and 3 degrees,
      respectively), with acquisition counts/projection of 30, 60, 120 and 240 each. We
      adjusted the pixel counts of reconstructed images to be constant, by setting
      combination of sampling number and counts/projection (120 sampling number for 30
      counts/projection, 60 for 60, and 30 for 120). Among the 3 acquisition
      conditions, the small sampling number of 30 had large acquisition counts per
      direction, resulting in low signal to noise ratio. Under this condition, the
      resolution was slightly low, but the uniformity of images was high. The
      combination of OS-EM and smaller sampling projection number may be clinically
      useful with reduction of the examination time, which is also beneficial to reduce
      dead time for gamma-camera rotation.

PMID- 14651351
TI  - Dobutamine Tc-99m furifosmin SPECT in detection of coronary artery disease:
      evaluation of same day, rest-stress protocol.
AB  - The purpose of this study was to evaluate the feasibility and diagnostic accuracy
      of same day rest-stress myocardial perfusion SPECT (MP SPECT) protocol by using
      technetium-99m (Tc-99m) furifosmin in conjunction with dobutamine stress test in
      subjects in whom coronary artery disease (CAD) had been proven or excluded at
      coronary angiography (CA). The study group consisted of 25 patients (8 female and
      17 male with a mean age of 53.04 +/- 8.56 yrs) unable to perform treadmill
      exercise or unsuitable for pharmacologic vasodilator stress testing. Ten mCi (370
      MBq) of Tc-99m furifosmin was injected intravenously at rest. Sixty min after
      injection, planar and SPECT images were acquired. One hour later all patients
      underwent dobutamine stress test. At the peak stress, 20 mCi (740 MBq) of Tc-99m
      furifosmin was injected. Sixty min after stress dose injection, planar and SPECT
      images were acquired. Rest-stress planar and SPECT data were evaluated by using
      visual and quantitative analysis. Heart to adjacent organ (Heart/Lung; H/Lu and
      Heart/Liver; H/Li) activity ratios were calculated from anterior planar images by
      using regions of interest (ROI). SPECT data were interpreted by using 20 segment
      5 point scoring system from short axis and vertical long axis slices. The results
      of rest-dobutamine stress Tc-99m furifosmin MP SPECT were compared with CA
      results. There were statistically significant differences between H/Lu and H/Li
      ratios at rest and stress conditions. Heart/adjacent organ activity ratios were
      similar and significant statistical difference could not be found between CA
      positive and CA normal patients. Sensitivity, specificity and accuracy for Tc-99m
      furifosmin SPECT study were calculated as 90%, 80% and 84% for left anterior
      descending (LAD), 87%, 94% and 92% for left circumflex (LCx) and 67%, 86% and 80%
      for right coronary artery (RCA), respectively. Overall sensitivity, specificity
      and accuracy were calculated as 83%, 87% and 85%, respectively. According to the
      results obtained in this study, it may be concluded that same day rest-dobutamine
      stress Tc-99m furifosmin SPECT protocol is a feasible and accurate technique in
      the evaluation of CAD, especially in patients unable to perform treadmill
      exercise or unsuitable for pharmacologic vasodilator stress testing.

PMID- 14651352
TI  - Comparison of myocardial fatty acid metabolism with left ventricular function and
      perfusion in cardiomyopathies: by 123I-BMIPP SPECT and 99mTc-tetrofosmin
      electrocardiographically gated SPECT.
AB  - OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship
      with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy
      (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with
      cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched
      healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)
      methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF)
      electrocardiographically gated SPECT. As parameters of myocardial fatty acid
      metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were
      calculated from early and delayed planar images, while regional BMIPP uptake and
      washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection
      fraction (LVEF) were calculated as global parameters of perfusion and function,
      while regional TF uptake and wall thickening index were calculated as regional
      parameters of perfusion and function using the Quantitative Gated SPECT software.
      The differences in the parameters and the correlations between the parameters
      from the 2 studies were investigated by one-way ANOVA and multiple linear
      regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its
      washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression
      analysis, global BMIPP parameters showed no significant correlation with LVEF (p
      > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and
      HCM. According to the partial correlation coefficient, early H/M was the only
      significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple
      linear regression analysis on regional parameters showed regional BMIPP
      parameters had no correlation with regional function (p > 0.05) but had a
      significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM,
      regional BMIPP parameters showed significant multiple linear correlations with
      both regional function (p < 0.005) and perfusion (p < 0.0001). According to the
      partial correlation coefficients, delayed regional BMIPP uptake was the most
      significant factor for predicting regional function in HCM, while early regional
      BMIPP uptake was the only or the most significant factor for predicting regional
      perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and
      washout could not reflect LV function. In HCM, regional delayed BMIPP uptake
      might be useful for evaluating regional function. In DCM and HCM, early BMIPP
      uptake might be largely determined by myocardial perfusion.

PMID- 14651353
TI  - Comparison of direct radionuclide cystography and voiding direct cystography in
      the detection of vesicoureteral reflux.
AB  - PURPOSE: The aim of this study is to compare the results of direct radionuclide
      cystography (DRNC) and voiding cystourethrography (VCUG) in a group of children
      with a high suspicion of vesicoureteral reflux (VUR). METHODS: For this purpose,
      25 children were studied with both VCUG and DRNC. Among 50 ureter units able to
      be compared 39 ureter units did not show any VUR on either study. Eleven ureter
      units (10 children) had VUR either on one study or on both (VCUG and DRNC). In
      the children who had VUR on either study, a dimercaptosuccinic acid scintigraphy
      (DMSA) was performed to determine their cortical function. RESULTS: We identified
      the following four patterns: 1) Five ureter units (five children) read positive
      on DRNC who were negative on VCUG and four of these children had positive
      findings on DMSA; 2) Four ureter units (four children) read positive on VCUG who
      were negative on DRNC, and two of them had positive findings on DMSA; 3) Two
      ureters (one child) read positive in both studies and also had abnormal DMSA
      findings; 4) Thirty-nine ureter units read as negative on both studies.
      CONCLUSION: Although the results of these two methods did not show a significant
      difference, DRNC offers a high sensitivity in the younger age group whereas VCUG
      seems to be more sensitive in the older age group. DRNC also offers continuous
      recording during the study, ease of assessment and lower radiation dose to the
      gonads, which makes it a preferable method for the initial diagnosis and follow
      up of VUR.

PMID- 14651354
TI  - Augmentation effects of lymphocyte activation by antigen-presenting macrophages
      on FDG uptake.
AB  - OBJECTIVE: Research on FDG-uptake by blood cells has revealed that FDG is
      incorporated by macrophages and granulocytes, as well as activated lymphocytes.
      These characteristics of FDG suggest the possibility of visualizing the
      distribution of immunocytes in target organs. The aim of this study was to
      investigate if mouse spleen-derived lymphocytes, activated by macrophages
      presenting sheep red blood cell (sRBC) antigens, could be traced by FDG. METHODS:
      One percent of a sRBC suspension was injected into the peritoneal cavity of mice
      thereby creating immunity to the sRBC antigen. The splenocytes, consisting mostly
      of lymphocytes, were isolated, and serum containing the anti-sRBC antibody was
      mixed with sRBC to prepare sRBC-antibody complexes (sRBC-AbCs). Then five percent
      of a thioglycolate medium was injected into the peritoneal cavity of the same
      mice, and macrophages of ascitic cell origin were obtained. These macrophages
      were added to the sRBC-AbCs to induce sRBC antigen presenting macrophages. These
      were incubated with splenocytes obtained from sRBC immunized mouse (sRBC
      immunized splenocytes) or non-immunized splenocytes to induce a T cell immune
      response. [3H]deoxyglucose ([3H]DG) and FDG were incorporated in splenocytes, and
      the quantity of their uptake was measured. RESULTS: [3H]DG uptake by sRBC
      immunized splenocytes was about eleven times as high as that of non-immunized
      splenocytes. In contrast, [3H]DG uptake by sRBC-immunized splenocytes, co
      cultured with macrophages phagocytizing sRBC-AbCs, was about 40 times higher
      compared with non-immunized splenocytes. Splenocytes in non-immunized mice picked
      up very little [3H]DG, despite co-culture with macrophages phagocytizing sRBC
      AbCs. Similar tendencies were observed with FDG. CONCLUSIONS: These results
      suggest that the SUV calculated in PET reflects not only the number of
      lymphocytes, but also the activation state of the lymphocytes themselves. In
      addition, the biodistribution of antigen specific lymphocytes, that have been
      taken up FDG in vitro and returned to the body, can be observed through PET.

PMID- 14651355
TI  - Comparison of methods for determination of glomerular filtration rate: Tc-99m
      DTPA renography, predicted creatinine clearance method and plasma sample method.
AB  - BACKGROUND: The gamma camera uptake method with Tc-99m-DTPA is simple and less
      time consuming for the determination of the glomerular filtration rate (GFR).
      However, its diagnostic accuracy is debated. Gates' method and predicted
      creatinine clearance method were compared with plasma clearance method with Tc
      99m-DTPA for the measurement of GFR. MATERIALS AND METHODS: Tc-99m-DTPA
      renography was performed on 133 patients (69 males and 64 females; age range
      being 24 to 84 years) with a wide range of renal function. The GFR was determined
      simultaneously by 3 methods; (1) gamma camera uptake method (modified Gates,
      Gates); (2) predicted creatinine clearance method (Cockcroft-Gault, CG); (3)
      single- or two-plasma clearance method (plasma sample clearance method, PSC). The
      PSC was chosen as a reference. RESULTS: The regression equation of the Gates and
      the CG against the PSC was Y = 11.89 + 1.041X (r = 0.790, p < 0.001, RMSE = 23.55
      ml/min/1.73 m2) and Y = 8.845 + 0.7899X (r = 0.8270, p < 0.001, RMSE = 16.27
      ml/min/1.73 m2), respectively. In comparison with the GFR by PSC, the Gates
      tended to overestimate the GFR, and contrarily the CG tended to underestimate the
      GFR. CONCLUSION: The Gates correlates well with the PSC. However, the Gates is
      even less precise than the CG. The Gates' method in Tc-99m-DTPA renography is not
      suitable for the estimation of GFR in routine practice.

PMID- 14651356
TI  - Decreased striatal D2 receptor density associated with severe behavioral
      abnormality in Alzheimer's disease.
AB  - OBJECTIVES: Since patients manifesting behavioral and psychological symptoms of
      dementia (BPSD) are a burden for their families and caregivers, the underlying
      neurobiological mechanism of this condition should be clarified. Using positron
      emission tomography (PET), we previously reported that wandering behavior in
      dementia was associated with a disturbed dopaminergic neuron system. We herein
      investigated the relationship between the severity of BPSD and the striatal D2
      receptor density in Alzheimer's disease (AD). METHODS: Ten patients with probable
      AD as per the National Institute of Neurological and Communicative Disorders and
      Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and
      five normal subjects were examined with PET. The tracer used was [11C]raclopride
      (D2 antagonist). The uptake of [11C] raclopride was calculated as the estimation
      of binding potential (BP) of the striatum to the cerebellum. The AD patients were
      institutionalized in multiple nursing homes, and their BPSD were evaluated by the
      Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale
      (Reisberg). RESULTS: There was a significant inverse Spearman's correlation
      between BEHAVE-AD-FW score and the BP, especially between the score of the
      behavioral domain and the BP values. The BP was found to be lower in severer BPSD
      patients. CONCLUSIONS: Patients with AD who manifest severe BPSD may have some
      dysfunction of striatal dopamine metabolism compared with those without BPSD.

PMID- 14651357
TI  - Improved accuracy in estimation of left ventricular function parameters from QGS
      software with Tc-99m tetrofosmin gated-SPECT: a multivariate analysis.
AB  - The purpose of this study was to verify whether the accuracy of left ventricular
      parameters related to left ventricular function from gated-SPECT improved or not,
      using multivariate analysis. METHODS: Ninety-six patients with cardiovascular
      diseases were studied. Gated-SPECT with the QGS software and left
      ventriculography (LVG) were performed to obtain left ventricular ejection
      fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV). Then,
      multivariate analyses were performed to determine empirical formulas for
      predicting these parameters. The calculated values of left ventricular parameters
      were compared with those obtained directly from the QGS software and LVG.
      RESULTS: Multivariate analyses were able to improve accuracy in estimation of
      LVEF, EDV and ESV. Statistically significant improvement was seen in LVEF (from r
      = 0.6965 to r = 0.8093, p < 0.05). Although not statistically significant,
      improvements in correlation coefficients were seen in EDV (from r = 0.7199 to r =
      0.7595, p = 0.2750) and ESV (from r = 0.5694 to r = 0.5871, p = 0.4281).
      CONCLUSION: The empirical equations with multivariate analysis improved the
      accuracy in estimating LVEF from gated-SPECT with the QGS software.

PMID- 14651358
TI  - Comparison of barium swallow, CT and thallium-201 SPECT in evaluating responses
      of patients with esophageal squamous cell carcinoma to preoperative
      chemoradiotherapy.
AB  - The aims of this study were to compare the results of thallium-201 (Tl-201)
      SPECT, barium swallow and CT in the assessment of the effect of preoperative
      chemoradiotherapy. This study consisted of 28 patients with advanced esophageal
      squamous cell carcinoma (AESCC) who underwent the three imaging modalities before
      and after preoperative chemoradiotherapy. The results were quantified using the
      bidimensional method for barium swallow and contrast-enhanced CT and the tumor-to
      lung ratio for SPECT. The percent decrease in these quantitative values after
      therapy was defined as %Dba, %Dct and %Dtl respectively. The histological effect
      of the chemoradiotherapy was determined from the resected surgical specimen of
      the esophagus: grade 0, 100% viable tumor cells; grade 1a, 99-67%; grade 1b, 66
      34%; grade 2, 33-1%; grade 3, no viable cells. A statistically significant
      difference of %Dtl between the subgroups of each grade was evident (p = 0.0433),
      whereas no significant differences were evident for %Dba (p = 0.1778) or %Dct (p
      = 0.7377). However, the overlap of %Dtl between these groups was marked. Although
      thallium-201 SPECT cannot be used to evaluate the therapeutic effect with
      acceptable accuracy, SPECT may be of additional value to barium swallow and CT in
      assessing the response of AESCC to preoperative chemoradiotherapy.

PMID- 14651359
TI  - Lipoma arborescens; successfully treated by yttrium-90 radiosynovectomy.
AB  - Although radiosynovectomy (RS) applications have been carried out for many years,
      clinical indications of this non-invasive procedure is thought to be limited
      probably due to the lack of information of clinicians. Clinicians' preferential
      indication for RS is the treatment-resistant synovitis of individual joints, i.e.
      despite systemic pharmacotherapy and intra-articular steroid injections. We
      present here a case of "lipoma arborescens" treated by yttrium-90, which is a
      rare intra-articular lesion characterized by villous proliferation of the
      synovial membrane and hyperplasia of subsynovial fat. The results of clinical,
      biochemical and hematological examinations, magnetic resonance (MR) imaging,
      arthroscopy and histological analysis have shown that the etiology was lipoma
      arborescens in a female patient, aged 36 having swelling and sometimes
      associating pain at her right knee for 4 years. We have applied to our patient's
      right knee RS with 185 MBq yttrium-90 colloid together with 40 mg of
      methylprednisolone acetate, although in our literature survey we have not met any
      similar case being treated with such indication. Even a year after the
      application, the patient has absolutely benefited from the treatment clinically,
      and this was also confirmed by comparative MR images (pre- and post-treatment).
      Consequently, we consider that Y-90 treatment might be applicable in suitable
      cases with lipoma arborescens.

PMID- 14651360
TI  - A case of lung cancer associated with pneumoconiosis diagnosed by fluorine-18
      fluorodeoxyglucose positron emission tomography.
AB  - We report a case of lung cancer arising from progressive massive fibrosis (PMF)
      associated with pneumoconiosis. In this case, fluorine-18 fluorodeoxyglucose
      positron emission tomography (FDG-PET) was able to clearly distinguish the lung
      cancer from PMF, suggesting a potential usefulness of FDG-PET in cancer screening
      in patients with pneumoconiosis. To our knowledge, this is the first description
      of an FDG-PET image of lung cancer arising from PMF.

PMID- 14651361
TI  - The usefulness of 99mTc-hexamethylpropyleneamineoxime white blood cell
      scintigraphy in a patient with eosinophilic gastroenteritis.
AB  - White blood cell (WBC) 99mTc-hexamethylpropyleneamineoxime (HMPAO) scintigraphy
      was performed in a patient with eosinophilic gastroenteritis. WBC accumulation
      was detected in the terminal ileum to descending colon, and pathological studies
      demonstrated eosinophilic infiltration at the same region. 99mTc-HMPAO-WBC
      scintigraphy was proved to be a useful tool for the detection of eosinophilic
      infiltration in eosinophilic gastroenteritis.

PMID- 14651362
TI  - Changes in myocardial oxidative metabolism after biventricular pacing as
      evaluated by [11C]acetate positron emission tomography.
AB  - A 70-year-old woman with dilated cardiomyopathy and recurrent severe heart
      failure was admitted for biventricular pacing (BVP), which was recently reported
      to have clinical efficacy for severe heart failure with intraventricular
      conduction delay. An electrocardiogram showed complete left bundle branch block,
      and the QRS interval was markedly prolonged at 195 msec. Echocardiogram showed
      marked dilatation, diffuse hypokinesis and dyssynchrony of the left ventricle,
      and grade III mitral valve regurgitation. The patient underwent implantation of
      an atriobiventricular pacemaker and three pacing leads transvenously. The QRS
      interval shortened to 165 msec immediately after the BVP therapy, and
      improvements in echocardiographic parameters were seen at 5 months after BVP
      therapy. Myocardial oxidative metabolism was assessed by the monoexponential
      clearance rate of [11C]acetate (Kmono) as measured by positron emission
      tomography (PET), and myocardial efficiency was assessed by the work metabolic
      index (WMI) at 1 and 5 months after the BVP therapy. The PET images obtained 5
      months after BVP therapy showed a decrease in the clearance of [11C]acetate
      compared with that obtained 1 month after BVP therapy. The Kmono of the whole
      left ventricle decreased from 0.051 at 1 month to 0.038 min-1 at 5 months after
      BVP therapy, and that of the septum, anterior wall, lateral wall and posterior
      wall also decreased. The WMI increased from 4.2 x 10(6) to 6.8 x 10(6) mmHg.
      ml/m2. These results suggest that BVP improved left ventricular function without
      increasing myocardial oxidative metabolism, resulting in improved myocardial
      efficiency, and that BVP may improve the long-term prognosis of heart failure
      patients with ventricular dyssynchrony. [11C]acetate PET is a useful method of
      evaluating global and regional myocardial oxidative metabolism in patients who
      have undergone BVP therapy.

PMID- 14651363
TI  - Neurofibroma with increased uptake of [F-18]-fluoro-2 deoxy-D-glucose interpreted
      as a metastatic lesion.
AB  - We report a patient with a solitary spinal neurofibroma in the posterior
      mediastinum interpreted as a metastatic tumor. A 46-year-old female with rectal
      cancer who had undergone operation and subsequent adjuvant chemotherapy two years
      previously was referred to our department for a follow-up whole body FDG-PET
      study. PET scan revealed a mass with increased uptake of FDG (SUV = 4.6) in the
      posterior mediastinum. MRI examination showed a dumbbell neurogenic tumor
      originating from the intercostal nerve at T6 level. A subsequent CT-guided biopsy
      demonstrated a neurofibroma.

PMID- 14651364
TI  - What is the diagnosis? Uveal malignant melanoma.

PMID- 14651365
TI  - The role of thallium-201 whole body scan with pelvic SPECT in patients with
      uterine cervical cancer treated by radiation therapy: a preliminary report.
AB  - Evaluation of tumor extent before treatment and its response to therapy is
      important. The aim of this report is to assess the usefulness with thallium-201
      (Tl-201) imaging study including whole body scan and pelvic single photon
      emission computed tomography (SPECT) in patients with uterine cervical cancers
      treated by radiation therapy. Before irradiation, eleven patients received
      detailed physical examination and Tl-201 imaging studies. A 4-score grading
      system was set for evaluation. The interval between Tl-201 imaging follow-up and
      completion of radiotherapy is one to four months, and its findings were compared
      with those from CT scan and clinical evidence. Before radiation, left
      supraclavicular and paraaortic lymphadenopathy was identified in one patient from
      whole body scan. Accumulation of Tl-201 uptake is observed from pelvic SPECT in
      all patients. It seems that patients with more tumor bulk had more intense
      uptake, except for one case with history of suspected pelvic inflammatory disease
      (PID). After radiotherapy, complete or partial regression is observed. For 6
      patients with complete regression (score = 0), no evidence of recurrence is
      confirmed by follow-up examinations. For three patients with little residual
      uptake (score = 1), one is suspected with residual density and she is under close
      follow-up, the other two patients seem due to uterine myoma or short latency.
      These three patients received another Tl-201 scan 6 months after irradiation
      completion and the score became zero. One patient with residual intense uptake
      (score = 2) suffered from relapse in the pelvis and abdomen. This preliminary
      report indicates that Tl-201 whole body scan and pelvic SPECT has potential in
      the assessment of response to radiotherapy in patients with uterine cervical
      cancers. However, further studies including more cases and longer follow-up are
      needed.

PMID- 14651366
TI  - Preliminary evaluation of image reconstruction by ordered-subset expectation
      maximization in thallium-201 lung scintigraphy.
AB  - OBJECTIVES: We observed whether clearer tumor delineation and greater tumor to
      non-tumor (T/N) count ratios could be obtained using an iterative ordered-subsets
      expectation maximization (OSEM) algorithm than conventional filtered-back
      projection algorithm (FBP) in the image reconstruction of thallium-201 (201Tl)
      lung scintigraphy. METHODS: In 29 patients with lung cancer and phantom studies,
      tomograms were reconstructed using FBP and OSEM algorithms, with and without a
      prefilter (Butterworth filter: BW), whose cut-off frequencies were 0.10
      cycles/pixel for FBP and 0.10 and 0.17 cycles/pixel for OSEM. Visual
      interpretation and tumor to non-tumor (T/N) count ratios were obtained and
      compared. RESULTS: Without a prefilter, T/N ratios from OSEM and FBP were 1.89 +/
      0.31 (early) and 2.00 +/- 0.54 (late) for OSEM, 1.90 +/- 0.33 (early) and 2.05
      +/- 0.59 (late) for FBP, respectively. The OSEM reconstruction without
      prefiltering showed clearer tumor contours than FBP without a prefilter.
      Incorporation of BW showed visually low-noised images but decreased T/N ratios in
      both reconstructions with BW (0.10 cycles/pixel). No greater T/N ratios were
      obtained by OSEM than FBP, with or without prefiltering. With BW with a cut-off
      frequency of 0.17 cycles/pixel, the same T/N ratios as those without BW were
      obtained. The tumor model sized 0.9 cm in the phantom study was invisible in both
      OSEM and FBP reconstructions without a prefilter, but visible with a prefilter.
      The influence of prefiltering on T/N ratios was also observed in phantom studies.
      CONCLUSIONS: Visually improved tumor delineation could be obtained in OSEM
      reconstruction without a prefilter as compared to FBP reconstruction without a
      prefilter for tumors greater than 2 cm. Prefiltering should be incorporated into
      OSEM reconstruction in diagnosing small tumors. However, the influence of
      prefilter (BW) setting on semi-quantitative interpretation needs further
      discussion.

PMID- 14651367
TI  - Re: Hung CJ, et al. Annals of Nuclear Medicine 17: 213-218, 2003.

PMID- 14651368
TI  - Celebrating 40 years of service, advocacy, and leadership within the Student
      National Medical Association 2003-2004 programmatic agenda.

PMID- 14651369
TI  - Comparison of blood pressure between Indiana AMA and NMA members.
AB  - OBJECTIVE: 1) To determine whether African-American physicians, compared to
      caucasian physicians, were at increased risk to develop hypertension; and 2) to
      determine whether physicians' knowledge of cardiovascular risk factors influenced
      their pattern of exercise. DESIGN: A mailed survey of members of the American
      Medical Association (AMA) and the National Medical Association (NMA) was
      completed to assess health status and plans for retirement. RESULTS: High-normal
      blood pressure was defined as systolic blood pressure of 85-89 mmHg. Mild (stage
      1) hypertension was defined as systolic blood pressure of 140-159 mmHg and
      diastolic blood pressure of 90-99 mmHg. Gender (male), age, and body mass index
      (BMI) were significantly correlated with elevated levels of selected blood
      pressure measures. Using regression analysis to control for gender, age, and BMI,
      ethnicity was identified as a fourth factor accounting for elevated blood
      pressure. NMA physicians had 3.25 times the risk of having systolic blood
      pressure in the mild (stage-1) hypertension range, 5.78 times the risk for blood
      pressure in the high-normal diastolic hypertension range, and 5.19 times the risk
      for blood pressure in the mild (stage-1) diastolic hypertension range. Medical
      specialty and type of psychological support were not significant predictors of
      elevated blood pressure. CONCLUSION: These data suggest that African-American
      physicians may be at an increased risk to develop abnormal blood pressure,
      compared to caucasian physicians, potentially affecting the number of physicians
      available to minority communities.

PMID- 14651370
TI  - Morbidity in relation to stage of diabetic nephropathy in type-2 diabetic
      patients.
AB  - AIMS OF THE STUDY: Type-2 diabetic patients have excessive cardiovascular
      mortality, primarily related to diabetic nephropathy. The extent of the morbidity
      due to nephropathy in type-2 diabetes mellitus has not been fully quantified in
      Nigeria. This study aims to quantify the prevalence of micro- and macrovascular
      complications in hospitalized type-2 diabetic patients with nephropathy. METHODS:
      Over a three-year period, 465 type-2 diabetic patients were examined for
      nephropathy and diabetic associated diseases while on hospital admission.
      RESULTS: One-hundred-ninety-one patients (41.1%) had signs of different stages of
      diabetic nephropathy. There is a predominance of the male sex in the nephropathic
      groups. Disease duration is lowest in the non-nephropathic group (6.5+/-7.1
      years) but varies between 9.4+/-4.1 years and 11.7+/-3.5 years in the
      nephropathic groups. Hypertension, left ventricular hypertrophy, stroke, and
      myocardial infarction were less common in the non-nephropathic group, p<0.05, but
      showed an upward trend with progression of nephropathy. Although foot amputation
      was uncommon, the total percentage of patients with diabetic foot increased with
      progression of nephropathy (17% in non-nephropathic group versus 67% in patients
      with chronic renal insufficiency). The overall prevalence of diabetic retinopathy
      increased with progression of nephropathy, especially the occurrence of
      proliferative retinopathy. CONCLUSIONS: A high morbidity was already present even
      in patients without nephropathy that increased in the course of the development
      of nephropathy. The study identifies patients with diabetic nephropathy as a high
      risk group for excess cardiovascular morbidity in Nigeria. Thus, it is imperative
      to aggressively prevent or slow down progression of diabetic nephropathy.

PMID- 14651371
TI  - Hypertension and medical informatics.
AB  - BACKGROUND: Only about 27% of Americans with hypertension have their disease
      under control. Hypertension in the African-American population has a higher
      prevalence (32%) and is less likely to be treated or controlled compared with
      that in the caucasian population. Hypertension places a significant burden on
      patients and health care systems. Applications of medical informatics can
      facilitate the management of hypertension. Examples that illustrate the utility,
      status, and future potential of medical informatics applications in the treatment
      of hypertension are presented. METHODS: Relevant studies and review articles were
      accessed through a PubMed search of the English-language literature and for
      current Internet-based information for the time period of 1993-2002. Search terms
      included, but were not limited to, hypertension, medical informatics, medical
      information science, electronic medical records, Internet, and managed care.
      RESULTS: There is evidence that medical informatics has a favorable impact on
      health care issues as it relates to patients and physicians. Although the use of
      computers to assist in managing hypertension is in its infancy, there are
      examples where informatics applications have a demonstrated clinical value.
      CONCLUSIONS: Management of hypertension needs much improvement. The use of
      computers and the Internet in health care is expanding and expected to have a
      positive impact on the management of chronic diseases, such as hypertension.

PMID- 14651373
TI  - African Americans' knowledge about organ donation: closing the gap with more
      effective persuasive message strategies.
AB  - In spite of increasing interest in the area of African Americans' willingness to
      donate organs, little empirical knowledge exists that can be used to create more
      effective public communication campaigns. In this study, 310 African Americans
      responded to seven knowledge items (based on myths and misconceptions about organ
      donation) shown in past studies to discriminate between donors and nondonors. The
      rate of accurate responses varied from 33% to 78% to individual knowledge items.
      Beliefs that the organ allocation system is inequitable (favoring whites and the
      rich) and the belief that donors pay extra medical bills strongly distinguished
      donors from nondonors. In addition, the information sources reported by African
      Americans willing to donate were more likely to include family members.
      Implications of these findings to the development of more effective organ
      donation campaigns targeting African Americans are offered.

PMID- 14651372
TI  - Exploring the relationship of conspiracy beliefs about HIV/AIDS to sexual
      behaviors and attitudes among African-American adults.
AB  - Conspiracy beliefs about HIV/AIDS have been endorsed by significant percentages
      of African Americans in prior research. However, almost no research has
      investigated the relationship of such beliefs to behaviors and attitudes relevant
      to HIV risk. In the present exploratory study, 71 African-American adults (aged
      18-45; 61% female) in the United States participated in a national, cross
      sectional telephone survey examining the relationship of HIV/AIDS conspiracy
      beliefs to sexual attitudes and behaviors. Results indicated significant
      associations between endorsement of a general HIV/AIDS government conspiracy and
      negative beliefs regarding condoms and greater numbers of sexual partners.
      Endorsement of HIV/AIDS treatment conspiracies was related to positive attitudes
      about condoms and greater condom use intentions. Findings suggest that conspiracy
      beliefs have implications for HIV prevention in African-American communities.

PMID- 14651374
TI  - The impact of using a low-literacy patient education tool on process measures of
      diabetes care in a minority population.
AB  - This study evaluated the current level of diabetes care in three county clinics
      serving an underserved minority population and determined if a low-literacy,
      diabetes reminder card would enhance certain diabetes process care measures.
      Patients from two intervention sites were given the low-literacy, diabetes
      reminder card. Two-hundred-nineteen patients (87%) showed the card to their
      provider, and 209 charts were reviewed. American Diabetes Association guidelines
      had been met 37%, 71%, and 41% for foot exam, and urine and lipid tests,
      respectively, at the time the card was given to the patients. Of the patients who
      needed a foot exam, urine test, and lipid panel that day (based on ADA
      guidelines), 48%, 67%, and 35% received them, respectively (card effect). In the
      third (nonintervention) site, charts of 218 patients were reviewed. Guidelines
      met were 95%, 89%, and 45% for foot exam, urine and lipid tests, respectively.
      Interestingly, standardized progress notes containing the first two (but not the
      third) process measures were used at this site. We conclude that although low
      literacy reminder cards did improve the ordering of process measures somewhat,
      they were not as effective as the utilization of progress forms with specific
      diabetes-related measures.

PMID- 14651375
TI  - Directly observed short course therapy for tuberculosis--a preliminary report of
      a three-year experience in a teaching hospital.
AB  - SETTING: The Chest Clinic of Obafemi Awolowo University Teaching Hospitals
      Complex (OAUTHC), Ile-Ife, southwest Nigeria is a referral center for
      tuberculosis patients in the region. Directly Observed Treatment Short Course
      (DOTS) has been in operation in the center since 1996. OBJECTIVE: To review the
      outcome of patients on DOTS with the aim of determining factors that may
      influence compliance. METHODS: Tuberculosis patients were placed on different
      treatment regimens according to the recommendation of the International Union
      Against Tuberculosis and Lung Disease (IUATLD) and the Nigerian Tuberculosis and
      Leprosy Control Program (NTBLCP). The results were recorded and evaluated
      periodically by the clinic staff under central supervision. The outcome of
      treatment over a three-year period (1996-1999) was reviewed. RESULTS: Five
      hundred-seventy-one patients were treated during this period. Cure/treatment
      completed rate was 86.1%, and compliance rate was 93.8%. Age, sex category of
      treatment, and distance from hospital had no significant influence on drug
      compliance. CONCLUSION: DOTS is an effective means of administering anti-TB
      drugs. Efforts should be channeled towards developing strategies for implementing
      DOTS in a more efficient way.

PMID- 14651376
TI  - Use of a web site to increase knowledge and awareness of hunger-related issues.
AB  - The purpose of this study was to determine the current level of knowledge and
      awareness of hunger-related issues among a convenience sample of Delawareans. We
      also assessed whether raising knowledge and awareness of the hunger problem
      through the FBD's newly designed web site would encourage participation in
      antihunger activities. Via e-mail, 1,719 individuals were invited to participate
      in a three-phase, online survey, and 392 agreed. Phase-I questions were answered
      prior to viewing the web site, phase II (n=217) immediately afterward, and phase
      III (n=61) six weeks later. Responses indicated a high level of awareness about
      general hunger issues but specific knowledge proved to be at a lower level. No
      statistically significant differences were noted when data were collapsed across
      gender, age, educational level, or work setting. In a six-week post-survey, 41%
      of subjects were motivated by the web site to engage in an antihunger activity;
      34% had told others about the web site and indicated it may be a useful tool in
      antihunger outreach efforts for the FBD.

PMID- 14651377
TI  - Salmonella epidural abscess in sickle cell disease: failure of the nonsurgical
      treatment.
AB  - In patients suffering from sickle cell disease (SCD), bone is a preferred site of
      infection. We report the case of a five-year-and-eight-month-old black African
      boy with homozygous-SS disease who developed a cranial epidural abscess. This
      intracranial infectious complication originated from a Salmonella enteritidis
      osteitis of the frontal bone. Antibiotic treatment alone did not control the
      disease, so surgery was necessary to remove the necrotic bone and to evacuate the
      epidural pus. The numerous factors interfering with normal healing of a septic
      focus in sickle cell anemia, particularly in this previously undescribed
      intracranial complication, emphasize the need for a primary and early surgical
      treatment in similar situations.

PMID- 14651378
TI  - Fever of unknown origin.
AB  - This is a case study of a 26-year-old Hispanic male who presented with an initial
      complaint of fevers, chills and generalized weakness for three weeks. Patient
      reported a classical history of diurnal fever with temperature spikes as high as
      105.8F after returning from a trip to Guatemala. His symptoms had waxed and waned
      for 3 weeks. This case study will focus on the initial presentation, value of
      complete history and physical exam, use of laboratory data and use of specialized
      diagnostic procedures in the outpatient setting. This case proves to be highly
      relevant to primary care in the context of treating patients with fevers of
      unknown etiology. Primary care physicians should be alert for unusual diseases in
      patients who are returning from foreign travel. Malaria is a potentially fatal
      disease that can be acquired by travelers to certain areas of the world,
      primarily developing nations. Transmitted through the bite of the Anopheles
      mosquito, malaria usually presents with fever and a vague systemic illness. The
      disease is diagnosed by demonstration of Plasmodium organisms on a specially
      prepared blood film. This case study speaks to the importance of prompt work up
      and treatment of fever of unknown origin that presents in an unusual clinical
      picture or that is not readily explainable.

PMID- 14651379
TI  - Stress, adverse pregnancy outcomes, and African-American females.

PMID- 14651380
TI  - In search of the RD degree: a challenge to the class of 2003 and beyond.

PMID- 14651381
TI  - NMA should advocate a national moratorium on the death penalty.

PMID- 14651382
TI  - LOHIA bill proposal.

PMID- 14651383
TI  - Rising prevalence of diabetes in China.

PMID- 14651384
TI  - Occupational asthma--Part II.

PMID- 14651385
TI  - Issues in electronic research publishing: implications for occupational health
      care.
AB  - Electronic publishing (e-publishing) is a global effort to make new scientific
      findings freely available to the public at the earliest possible time in a
      centralized Internet repository. Several journals modeled after the PubMedCentral
      concept offer central and efficient access to biomedical literature while
      balancing open communication with publishing obligations. Supporters of e
      publishing indicate that convenient access to the most current scientific
      literature in multimedia formats affords occupational and other health care
      providers tools to supplement practice, answer clinical questions, and network
      with other professionals. Non-supporters claim that e-publishing may compromise
      the peer review process, promote weak research and the use of non-scientifically
      endorsed information, and present technical difficulties to users. Accepting e
      publishing requires considering all users and producers of scientific information
      as potential vehicles to conduct, communicate, disseminate, and retrieve
      scientific research. The transition will occur more smoothly if standards,
      including costs, for e-publishing are established and implemented.

PMID- 14651386
TI  - Reaching managers at an industry association conference: evaluation of ergonomics
      training.
AB  - Managers rarely receive targeted safety and health training, despite the belief
      that management support is important for a successful workplace safety and health
      program. A program evaluation was performed on an ergonomics workshop for
      managers attending an industry association conference. The goals were to
      determine whether the conference was an effective setting for the training, to
      assess whether the training led to an increase in participants' knowledge and
      ability, and to determine whether participants could use what was taught in an
      applied exercise. The majority of participants (97%) believed the conference was
      an effective setting for the training. Participants' knowledge and ability to
      identify musculoskeletal risks increased significantly following the training.
      Additionally, participants were able to identify musculoskeletal risk factors and
      suggest solutions during the applied exercise. Occupational health nurses should
      consider trade association meetings as a venue for educational training sessions
      and for disseminating their research results.

PMID- 14651387
TI  - Exploring variables among medical center employees with injuries: developing
      interventions and strategies.
AB  - Data for this study were collected via retrospective chart review. The study
      shows the variables associated with work related injury (WRI) in Central Arkansas
      Veterans Healthcare System medical center employees from 1998 to 2000 in terms of
      age, gender, employment type, employment status, shift length, body mass index
      (BMI), workers' compensation claims prior to current employment, employee health
      and wellness activity attendance, lost time claims, medical/loss of productivity
      costs. Notable characteristics of injured employees included advancing age,
      female gender, long working hours, increased BMI, history of prior back and upper
      extremity injuries, no health and wellness activity attendance, and lost time
      with injury. Back and shoulder strain, falling accidents, and repetitive motion
      injuries were the most severe and costly injuries. Further study of medical
      center employees is warranted to determine risk factors for WRI and develop
      appropriate protective interventions and safety promotion strategies.

PMID- 14651388
TI  - Providing notice to employees on leave: Implications of Ragsdale versus Wolverine
      Worldwide, Inc.
AB  - Occupational health nurses must develop a perspective on implementation of the
      Family and Medical Leave Act (FMLA) that supports the provision of quality
      nursing care to employees and regulatory compliance by the employer. Public
      policy related to the FMLA continues to evolve with the states acting more
      rapidly than the federal government as laboratories for social change.
      Occupational health nurses must identify resources for staying current about new
      legislation and proposals to advise employers and facilitate regulatory
      compliance. Occupational health nurses should advise employers to provide written
      notice to employees designating leave taken under company leave policies as
      counting as employees' FMLA leave entitlement. These issues are important for
      regulatory compliance, and also for communication with and fair treatment of
      employees.

PMID- 14651389
TI  - Recognizing early signs of dementia at work.

PMID- 14651390
TI  - Falls prevention in rural general practice: what stands the test of time and
      where to from here?
AB  - OBJECTIVE: General practitioner recall of the 1992-96 'Stay on Your Feet' (SOYF)
      program and its influence on practice were surveyed five years post-intervention
      to gauge sustainability of the SOYF General Practice (GP) component. METHODS: A
      survey assessed which SOYF components were still in existence, current practice
      related to falls prevention, and interest in professional development. All
      general practitioners (GPs) situated within the boundaries of a rural Area Health
      Service were mailed a survey in late 2001. RESULTS: Response rate was 66.5%
      (139/209). Of 117 GPs in practice at the time of SOYF, 80.2% reported having
      heard of SOYF and 74.4% of those felt it had influenced practice. Half (50.9%)
      still had a copy of the SOYF GP resource and of those, 58.6% used it at least
      'occasionally'. Three-quarters of GPs surveyed (75.2%) checked medications
      'most/almost all' of the time with patients over 60 years; 46.7% assessed falls
      risk factors; 41.3% gave advice; and 22.6% referred to allied health
      practitioners. GPs indicated a strong interest in falls prevention-related
      professional development. There was no significant association between use of the
      SOYF resource package and any of the current falls prevention practices (all chi2
      > 0.05). CONCLUSIONS AND IMPLICATIONS: There was high recall of SOYF and a
      general belief that it influenced practice. There was little indication that use
      of the resource had any lasting influence on GPs' practices. In future, careful
      thought needs to go into designing a program that has potential to affect long
      term change in GPs' falls prevention practice.

PMID- 14651391
TI  - A study of the use of free nicotine patches by Indigenous people.
AB  - OBJECTIVE: To assess use of free nicotine patches by Indigenous people when
      offered a brief intervention for smoking cessation, and to assess changes in
      smoking behaviour at six months. METHODS: We conducted a pre and post study in
      three Indigenous communities in the Northern Territory. RESULTS: Forty Indigenous
      smokers self-selected to receive free nicotine patches and a brief intervention
      for smoking cessation, and 71 chose the brief intervention only. Eighty-four per
      cent of participants were followed up; 14% of participants could not be located.
      Fifteen per cent of the nicotine patches group (10% with CO validation) and 1%
      (CO validated) of the brief intervention only group reported that they had quit
      at six months. Seventy-six per cent of the nicotine patches group and 51% of the
      brief intervention only group had reduced their consumption of tobacco. No
      participant completed a full course of patches. One possible side effect--the
      experience of bad dreams--was attributed in one community to the person concerned
      having been 'sung' or cursed. CONCLUSIONS: Free nicotine patches might benefit a
      small number of Indigenous smokers. Cessation rates for the use of both nicotine
      patches and brief intervention alone were lower than those in other populations,
      possibly because the study was conducted in a primary care setting and because of
      barriers to cessation such as widespread use of tobacco in these communities and
      the perception of tobacco use as non-problematic.

PMID- 14651392
TI  - Nicotine replacement therapy products over the counter: real-life use in the
      Australian community.
AB  - OBJECTIVE: To explore the information received by NRT users; whether patterns of
      NRT use are in accordance with recommendations; and to identify the
      characteristics of those using NRT products. METHODS: A cross-sectional, omnibus
      telephone survey of 1,509 community members was conducted in New South Wales,
      Australia in 2000. The survey identified 215 current and former smokers who
      completed additional questions regarding their most recent quit attempt. RESULTS:
      Of the 215 current and former smokers, 67 (31.2%) had used NRT on their most
      recent quit attempt. The majority of NRT use (61%) lasted for less than two
      weeks. More than 40% of NRT users reported receiving no instructions from a
      doctor or pharmacist on how to use the product. Approximately one-third of NRT
      use was associated with concomitant smoking, with 10% of NRT use being associated
      with little or no reduction in reported daily cigarette consumption, Only 41.8%
      of NRT users reported a doctor had recommended using the product. CONCLUSIONS:
      Despite the small size of the sample, the data suggest a level of inappropriate
      use of NRT products in the community. IMPLICATIONS: Wider use and effective
      provision of support and advice to NRT users in the community must be addressed
      if this product is to achieve its optimal potential in aiding smoking cessation.

PMID- 14651393
TI  - Exposure to secondhand smoke at work: a survey of members of the Australian
      Liquor, Hospitality and Miscellaneous Workers Union.
AB  - OBJECTIVE: To measure workers' attitudes towards and experiences of exposure to
      secondhand smoke (SHS) in the workplace. METHOD: A stratified random sample of
      members from the Victorian Branch of the Australian Liquor, Hospitality and
      Miscellaneous Workers Union (LHMU) was interviewed by telephone in September
      2001. Of the 1,078 respondents surveyed (77% response rate), hospitality workers
      comprised 49% of the sample, while the remainder comprised community services,
      property services and manufacturing workers. RESULTS: Overall, 54% of union
      members were employed in workplaces that did not completely ban smoking and 34%
      reported being exposed to SHS during their typical working day. Workplaces with
      total smoking bans had a high level of compliance with these restrictions, with
      no workers in these settings indicating exposure to SHS at work. Compared with
      other workers, hospitality workers reported working in environments that had more
      permissive smoking policies. Consistent with this, 56% of hospitality workers
      said they were exposed to SHS during a typical day at work compared with 11% of
      other workers. Overall, 79% of workers expressed concern about exposure to SHS,
      including 66% of smokers. Compared with other workers, hospitality workers
      reported a higher level of concern about exposure to SHS at work. CONCLUSION:
      These findings provide evidence that many workers, and especially those employed
      in the hospitality sector, are exposed to SHS during their working day and are
      concerned about the effects of such exposure on their health. IMPLICATIONS: These
      findings indicate that workplace smoke-free policies are effective in reducing
      worker exposure to SHS and demonstrate support for the extension of smoke-free
      policies to hospitality workplaces.

PMID- 14651394
TI  - PSA testing and digital rectal examination in New Zealand.
AB  - OBJECTIVE: To investigate the use of digital rectal examination and prostate
      specific antigen (PSA) testing in a population-based sample of men in New
      Zealand. METHODS: A random selection of men aged 40-74 years, weighted by age,
      was chosen from the general electoral roll of New Zealand. Only men with a
      telephone who had been married at some time were eligible. Telephone interviews
      were conducted using a standard questionnaire. Crude and age-adjusted proportions
      were calculated. Logistic regression was used to explore associations between
      sociodemographic factors and digital rectal examination or PSA testing. RESULTS:
      Interviews were completed for 85% of the 1,486 eligible men and analyses were
      confined to the 1,225 European men. Many more men reported having a digital
      rectal examination (41%; 95% CI 33.8-48.2) than a PSA test (9%; 95% CI 4.2-14.2).
      Men in the lowest social class were significantly less likely to have had a
      digital rectal examination (OR 0.30; 95% CI 0.18-0.50) or PSA test (OR 0.25; 95%
      CI 0.11-0.60) compared with those in the highest social class. Men with
      vocational training or no post-school qualifications were approximately half as
      likely to report a digital rectal examination or a PSA test compared with men
      with degrees or diplomas. CONCLUSIONS: Although current New Zealand
      recommendations are that population screening for prostate cancer should not be
      introduced, many men are still having digital rectal examinations and PSA tests
      in the absence of symptoms. The frequency of PSA testing is considerably lower
      than in Australia and appears to be largely influenced by a man's social class.

PMID- 14651396
TI  - Home bowel cancer tests and informed choice--is current information sufficient?
AB  - OBJECTIVES: To evaluate the type of information that is available to purchasers
      of home-based bowel cancer test kits. METHODS: Manufacturers, pharmacies and
      independent testing programs were contacted to obtain faecal occult blood test
      (FOBT) kits. State cancer organisations were contacted for information on bowel
      cancer screening. Information on bowel cancer, the FOBT kit, the testing process
      and potential benefits and harms of the screening process were assessed using
      guidelines provided by the UK General Medical Council (GMC). RESULTS: FOBT kits
      and cancer organisation information provided adequate information on the purpose
      of screening, the screening process itself and potential benefits, but provided
      no information concerning uncertainties of screening or potential harms.
      CONCLUSIONS: On the basis of both the UK GMC criteria and patient desires for
      information, the information available at present falls short of being considered
      adequate for an informed decision to purchase a home-based FOBT. IMPLICATIONS: We
      must ensure adequate and balanced information is available to redress the present
      information asymmetry to facilitate informed participation in a potentially
      valuable public health initiative.

PMID- 14651395
TI  - Effects of variations in hysterectomy status on population coverage by cervical
      screening.
AB  - OBJECTIVES: To investigate geographic differences in hysterectomy rates and
      effects on estimated screening coverage in South Australia. METHODS: Hysterectomy
      data from South Australian hospitals for 1992-2000 were used to calculate age
      specific hysterectomy rates for 20-69 year old women by residential subregion and
      postcode. Regional variations in rates were used to estimate variations in
      proportions of women with an intact uterus. Effects on estimates of screening
      coverage were investigated. RESULTS: About 66% of South Australian women were
      estimated to have an intact uterus at 70 years of age, based on hysterectomy
      rates for 1992-2000. The proportion was smaller in lower than upper socio
      economic areas, and in country areas than the State capital (Adelaide). Estimates
      varied from 49% to 73% across 20 subregions. About 67% of 20-69 year olds with an
      intact uterus were estimated to have been screened in the 24-month period from
      2000 to 2001. Similar estimates applied to Adelaide and country areas,
      irrespective of whether adjustments were made for differences in hysterectomy
      rates. A lower screening coverage applied to lower than upper socio-economic
      areas of Adelaide, irrespective of whether these adjustments were made. While
      adjusting for variations in hysterectomy rates generally had little effect on
      estimated screening coverage, there were notable exceptions. For example, in one
      subregion, coverage increased among 50-69 year olds from 53% to 66%. CONCLUSIONS:
      Adjustments for variations in hysterectomy rates can affect estimated screening
      coverage in some localities. Such adjustments should be undertaken to better
      define areas of under-screening for targeting in screening promotion.

PMID- 14651397
TI  - Developing a charter of physical activity and sport for children and youth.
AB  - OBJECTIVES: The purpose of this project was to develop a Charter of Physical
      Activity and Sport for Children and Youth. Its primary purpose is to provide a
      philosophical framework to support participation, enjoyment and safety in
      physical activity and sport for all Australian children and youth. METHODS: The
      development of the charter was initiated by The Children's Hospital at Westmead,
      New South Wales (NSW) and was developed in consultation with 60 parent and
      community groups, sporting and recreational clubs and organisations, professional
      associations, schools, local and state government organisations and national
      sporting bodies. RESULTS: The charter emphasises that physical activity and sport
      should be a fundamental right of all children and youth; be enjoyable; enhance
      health and well-being; be available for children and youth with disabilities and
      chronic illness; include those who are geographically isolated; be safe and free
      from physical and psychological abuse; be free from exploitation for political,
      commercial or financial gain; avoid elitism; and be encouraged by a wide cross
      section of the community. CONCLUSIONS: Broad consensus has been reached by most
      organisations with a role or interest in child and youth sport and physical
      activity on the foundations for participation in these activities by young people
      living in NSW. IMPLICATIONS: Research and evaluation of practice in Australia is
      essential and will allow development of evidence-based guidelines for
      participation in physical activity and sport for young Australians, based on the
      philosophy of the charter.

PMID- 14651398
TI  - Health promotion in childcare centres: a survey of sun protection policy and
      practice.
AB  - OBJECTIVES: To describe sun protection policy and practice in child care centres
      in the Hunter region of New South Wales (NSW) and examine differences in sun
      protection policy and practice between those who attended a NSW Cancer Council
      SunSmart workshop and those who did not. METHOD: One hundred and seventy-seven
      Hunter child care centres completed a CATI interview (95% consent rate). RESULTS:
      Ninety seven per cent of centres reported having a written sun protection policy
      (only 5% deemed comprehensive by review). Sun protection policy components were
      reported more often than sun protection practices. There were no significant
      differences in policy or practice according to workshop attendance. CONCLUSIONS:
      Having a sun protection policy in place does not necessarily translate to sun
      protection practice at child care centres.

PMID- 14651399
TI  - Nifty after fifty: evaluation of a physical activity directory for older people.
AB  - OBJECTIVE: To develop a physical activity directory (PAD) for Brisbane people
      over the age of 50 years for distribution by two methods (given or requested),
      and to determine its effectiveness in raising awareness and encouraging older
      people to participate in local physical activity options. METHODS: Baseline
      demographic data and stage of change was collected from 224 participants who
      received the directory. Participants were interviewed by telephone six weeks
      later to determine their use of the directory on a number of dimensions. RESULTS:
      Most participants interviewed at follow-up remembered reading the directory.
      Participants who requested the directory were significantly more likely than
      those who were given it to: be contemplators, read the directory, plan to ring a
      number, plan to attend a class, and to share the directory with others.
      Participants who were contemplators were significantly more likely to have
      participated in physical activity of their own and rang a number from the
      directory. The directory increased over half the participants' awareness of local
      physical activity options, yet only 7% reported ringing a number and 15% reported
      doing their own physical activity. CONCLUSIONS: The directory was more effective
      in raising awareness about physical activity options than encouraging people to
      participate in physical activity, and participants with short-term plans to be
      more active were more likely to have used the directory. IMPLICATIONS: The
      directory, even when linked with other services, raises awareness about physical
      activity options, but has minimal short-term influence on participation.

PMID- 14651400
TI  - Australians' use of fake tanning lotions: another piece of the puzzle.
AB  - OBJECTIVE: To assess community attitudes and practices in relation to fake
      tanning lotions. METHODS: 1,509 New South Wales residents aged 15 years and over,
      selected at random, completed a computer-assisted telephone survey. RESULTS:
      Thirty-three per cent of respondents thought fake tanning lotions were unsafe. In
      relation to The Cancer Council marketing fake tanning lotions, more than three
      fifths thought The Cancer Council would be promoting tans, although 62% thought
      it would be a good thing as fake tans are safer than tanning in the sun. Nine per
      cent of respondents had used fake tanning lotions in the past 12 months. Almost
      half (48%) of female current users used fake tanning lotions occasionally or only
      for special occasions during the past summer. In particular settings, the
      sunscreen and hat-wearing practices of female users and non-users of fake tanning
      lotions differed significantly. CONCLUSION: There appears to be no consistent
      data to suggest that fake tanning lotions may be used as a safer alternative to
      sun tanning. However, there is a responsibility to at least disseminate accurate
      information on these products.

PMID- 14651401
TI  - Immunisation coverage in Australia corrected for under-reporting to the
      Australian Childhood Immunisation Register.
AB  - OBJECTIVE: To assess the level of under-reporting to the Australian Childhood
      Immunisation Register (ACIR) and the resulting underestimation of national
      immunisation coverage using ACIR data, and to correct national immunisation
      estimates for under-reporting. METHODS: A national population-based telephone
      survey was conducted in May-July 2001 of two random samples of children born in
      1998 and 1999 who were recorded on the ACIR as incompletely immunised at either
      12 months or 24 months of age. Parents were asked whether and when their child
      had received the vaccinations required to qualify as fully immunised. Survey data
      were then used to correct ACIR-derived coverage estimates at 12 and 24 months of
      age. RESULTS: Of 640 surveyed children in the 12-month group, 258 (40%) met the
      study definition of 'definitely immunised'. This adjusted the ACIR coverage
      estimate upwards by 2.7% to 94% (95% CI 93.6-94.1). Of 698 surveyed children in
      the 24-month group, 387 (55%) met the study definition of 'definitely immunised'
      at the second birthday. Adjusted coverage for doses due by 24 months was 89.8%
      (95% CI 89.6-90.1), 5% higher than recorded on the ACIR. CONCLUSIONS:
      Immunisation coverage in Australia for all scheduled vaccines due by 12 months of
      age is 94% and for all vaccines due by two years of age is almost 90%. The ACIR
      underestimates coverage by up to 5%. As the ACIR database relies on provider
      notification, published estimates of immunisation coverage are unlikely to rise
      significantly above current levels, unless mechanisms are put in place to further
      improve notification to the ACIR.

PMID- 14651402
TI  - Community attitudes towards environmental tobacco smoke in licensed premises:
      follow-up study after the Sharp case.
AB  - OBJECTIVE: To examine community attitudes towards environmental tobacco smoke in
      licensed premises after the Sharp case decision. METHOD: 723 randomly selected
      New South Wales residents aged 18 years and over completed a telephone survey in
      November 2001. RESULTS: The vast majority supported some form of smoking
      restriction in licensed clubs (92.1%) and hotels (90.0%). Compared with a 2000
      survey, respondents in the 2001 survey were significantly more likely to support
      a total smoking ban in licensed clubs and hotels. When support was assessed using
      a ban-only question, 66.8% supported banning smoking in pubs/clubs. Approximately
      half reported being less likely to visit non-eating areas of licensed clubs
      (51.2%) and hotels (49.8%) if smoking were permitted and these proportions were
      significantly higher than in the 2000 survey. A majority (83.1%) thought bar
      workers' health should be a major consideration when deciding how to handle
      smoking in pubs/clubs. More than half (56.8%) believed pubs/clubs would
      experience significant financial problems if smoking bans were introduced.
      CONCLUSIONS AND IMPLICATIONS: In New South Wales, majority support exists for
      banning smoking in pubs and clubs. Legislation banning smoking in all indoor
      drinking and gaming areas should be introduced immediately.

PMID- 14651403
TI  - Domestic violence in South Australia: a population survey of males and females.
AB  - OBJECTIVE: To determine the self-reported prevalence of domestic violence in
      South Australian adults and to examine the associated risk factors, demographic
      factors and related health issues using computer-aided telephone interviewing
      (CATI) methodology. SAMPLE: A representative random sample of South Australian
      adults aged 18 years and over selected from the Electronic White Pages. Overall,
      6,004 interviews were completed (73.1% response rate). RESULTS: In total, 17.8%
      of adults in South Australia reported some form of domestic violence by a current
      or an ex-partner. Demographic factors such as low household income, unemployment
      or part-time employment and health variables such as poor to fair self-reported
      health status and alcohol abuse problems were found to have a significant
      relationship with domestic violence. CONCLUSIONS: Approximately one in five South
      Australian adults report physical and emotional abuse from current or ex
      partners, of whom the majority are women who are separated, divorced or never
      married and on lower incomes. Telephone interviewing is a cost-effective method
      of identifying prevalence estimates of domestic violence when compared with data
      collection by way of police reports or hospital emergency statistics.
      IMPLICATIONS: Domestic violence is a serious public health concern often 'hidden'
      by the lack of appropriate data. This study has shown that domestic violence is
      frequent and has important social, economic and health consequences.

PMID- 14651404
TI  - The injection of methadone syrup in New South Wales: patterns of use and
      increased harm after partial banning of injecting equipment.
AB  - OBJECTIVE: To describe methadone injectors and the risk practices associated with
      injecting methadone in New South Wales, Australia. To assess the impact on
      injecting drug use and risk behaviour of the withdrawal of methadone injecting
      equipment from government-funded needle and syringe programs. METHOD: Cross
      sectional survey, conducted in 1999, of 206 people who had injected methadone at
      least once in the previous month. Participants were from Central Sydney, West
      Sydney and rural New South Wales. RESULTS: Of participants who had injected both
      methadone and other drugs in the previous month (n=162), significantly more
      reused their methadone injecting equipment compared with those who reused their
      other drug injecting equipment (60% vs. 28%, p<0.01). There was no significant
      difference in terms of sharing injecting equipment, with 19% reporting sharing
      methadone injecting equipment and 14% sharing other drug injecting equipment.
      However, women were more likely than men to share methadone injecting equipment.
      Over half of the participants had accessed diverted methadone and a substantial
      minority reported the use of public spaces for injecting methadone. CONCLUSIONS:
      Our results suggest that the current policy has led to increased reuse of
      equipment for injecting methadone. IMPLICATIONS: A range of other possible policy
      options, such as closer monitoring and dilution of take-home doses, increasing
      oral doses and implementing trials of injected methadone, may assist to reduce
      the prevalence of methadone syrup injection and related harms.

PMID- 14651405
TI  - Prevalence of smoking in Australia.

PMID- 14651406
TI  - The economic impact of smoke-free policies on sales in restaurants and cafes in
      Victoria.

PMID- 14651407
TI  - Poor knowledge and low coverage of hepatitis B vaccination among injecting drug
      users in Sydney.

PMID- 14651408
TI  - Tobacco in Australia: still a profitable venture?

PMID- 14651409
TI  - Are we doing enough for young people with chronic illness?

PMID- 14651410
TI  - The feasibility of applying item response theory to measures of migraine impact:
      a re-analysis of three clinical studies.
AB  - BACKGROUND: Item response theory (IRT) is a powerful framework for analyzing
      multiitem scales and is central to the implementation of computerized adaptive
      testing. OBJECTIVES: To explain the use of IRT to examine measurement properties
      and to apply IRT to a questionnaire for measuring migraine impact--the Migraine
      Specific Questionnaire (MSQ). METHODS: Data from three clinical studies that
      employed the MSQ-version 1 were analyzed by confirmatory factor analysis for
      categorical data and by IRT modeling. RESULTS: Confirmatory factor analyses
      showed very high correlations between the factors hypothesized by the original
      test constructions. Further, high item loadings on one common factor suggest that
      migraine impact may be adequately assessed by only one score. IRT analyses of the
      MSQ were feasible and provided several suggestions as to how to improve the items
      and in particular the response choices. Out of 15 items, 13 showed adequate fit
      to the IRT model. In general, IRT scores were strongly associated with the scores
      proposed by the original test developers and with the total item sum score.
      Analysis of response consistency showed that more than 90% of the patients
      answered consistently according to a unidimensional IRT model. For the remaining
      patients, scores on the dimension of emotional function were less strongly
      related to the overall IRT scores that mainly reflected role limitations. Such
      response patterns can be detected easily using response consistency indices.
      Analysis of test precision across score levels revealed that the MSQ was most
      precise at one standard deviation worse than the mean impact level for migraine
      patients that are not in treatment. Thus, gains in test precision can be achieved
      by developing items aimed at less severe levels of migraine impact. CONCLUSIONS:
      IRT proved useful for analyzing the MSQ. The approach warrants further testing in
      a more comprehensive item pool for headache impact that would enable computerized
      adaptive testing.

PMID- 14651411
TI  - The responsiveness of headache impact scales scored using 'classical' and
      'modern' psychometric methods: a re-analysis of three clinical trials.
AB  - BACKGROUND: While item response theory (IRT) offers many theoretical advantages
      over classical test theory in the construction and scoring of patient based
      measures of health few studies compare scales constructed from both methodologies
      head to head. OBJECTIVE: Compare the responsiveness to treatment of migraine
      specific scales scored using summated rating scale methods vs. IRT methods.
      METHODS: The data came from three clinical studies of migraine treatment that
      used the Migraine Specific Quality of Life Questionnaire (MSQ). Five methods of
      quantifying responsiveness were used to evaluate and compare changes from pre- to
      post-treatment in MSQ scales scored using Likert and IRT scaling methods.
      RESULTS: Changes in all MSQ scale scores from pre- to post-treatment were highly
      significant in all three studies. A single index scored from the MSQ using IRT
      methods was determined to be more responsive than any one of the MSQ subscales
      across the five methods used to quantify responsiveness. Across 13 of the 15
      tests (5 responsiveness methods * 3 studies) conducted, the single index scored
      from the MSQ using IRT methods was the most responsive measure. CONCLUSIONS: IRT
      methods increased the responsiveness of the MSQ to the treatment of migraine. The
      results agree with the psychometric evidence that suggest that it is feasible to
      score a single index from the MSQ using IRT methods. This approach warrants
      further testing with other measures of migraine impact.

PMID- 14651412
TI  - Calibration of an item pool for assessing the burden of headaches: an application
      of item response theory to the headache impact test (HIT).
AB  - BACKGROUND: Measurement of headache impact is important in clinical trials, case
      detection, and the clinical monitoring of patients. Computerized adaptive testing
      (CAT) of headache impact has potential advantages over traditional fixed-length
      tests in terms of precision, relevance, real-time quality control and
      flexibility. OBJECTIVE: To develop an item pool that can be used for a
      computerized adaptive test of headache impact. METHODS: We analyzed responses to
      four well-known tests of headache impact from a population-based sample of recent
      headache sufferers (n = 1016). We used confirmatory factor analysis for
      categorical data and analyses based on item response theory (IRT). RESULTS: In
      factor analyses, we found very high correlations between the factors hypothesized
      by the original test constructers, both within and between the original
      questionnaires. These results suggest that a single score of headache impact is
      sufficient. We established a pool of 47 items which fitted the generalized
      partial credit IRT model. By simulating a computerized adaptive health test we
      showed that an adaptive test of only five items had a very high concordance with
      the score based on all items and that different worst-case item selection
      scenarios did not lead to bias. CONCLUSION: We have established a headache impact
      item pool that can be used in CAT of headache impact.

PMID- 14651413
TI  - Applications of computerized adaptive testing (CAT) to the assessment of headache
      impact.
AB  - OBJECTIVE: To evaluate the feasibility of computerized adaptive testing (CAT) and
      the reliability and validity of CAT-based estimates of headache impact scores in
      comparison with 'static' surveys. METHODS: Responses to the 54-item Headache
      Impact Test (HIT) were re-analyzed for recent headache sufferers (n = 1016) who
      completed telephone interviews during the National Survey of Headache Impact
      (NSHI). Item response theory (IRT) calibrations and the computerized dynamic
      health assessment (DYNHA) software were used to simulate CAT assessments by
      selecting the most informative items for each person and estimating impact scores
      according to pre-set precision standards (CAT-HIT). Results were compared with
      IRT estimates based on all items (total-HIT), computerized 6-item dynamic
      estimates (CAT-HIT-6), and a developmental version of a 'static' 6-item form (HIT
      6-D). Analyses focused on: respondent burden (survey length and administration
      time), score distributions ('ceiling' and 'floor' effects), reliability and
      standard errors, and clinical validity (diagnosis, level of severity). A random
      sample (n = 245) was re-assessed to test responsiveness. A second study (n =
      1103) compared actual CAT surveys and an improved 'static' HIT-6 among current
      headache sufferers sampled on the Internet. Respondents completed measures from
      the first study and the generic SF-8 Health Survey; some (n = 540) were re-tested
      on the Internet after 2 weeks. RESULTS: In the first study, simulated CAT-HIT and
      total-HIT scores were highly correlated (r = 0.92) without 'ceiling' or 'floor'
      effects and with a substantial reduction (90.8%) in respondent burden. Six of the
      54 items accounted for the great majority of item administrations (3603/5028,
      77.6%). CAT-HIT reliability estimates were very high (0.975-0.992) in the range
      where 95% of respondents scored, and relative validity (RV) coefficients were
      high for diagnosis (RV = 0.87) and severity (RV = 0.89); patient-level
      classifications were accurate 91.3% for a diagnosis of migraine. For all three
      criteria of change, CAT-HIT scores were more responsive than all other measures.
      In the second study, estimates of respondent burden, item usage, reliability and
      clinical validity were replicated. The test-retest reliability of CAT-HIT was
      0.79 and alternate forms coefficients ranged from 0.85 to 0.91. All correlations
      with the generic SF-8 were negative. CONCLUSIONS: CAT-based administrations of
      headache impact items achieved very large reductions in respondent burden without
      compromising validity for purposes of patient screening or monitoring changes in
      headache impact over time. IRT models and CAT-based dynamic health assessments
      warrant testing among patients with other conditions.

PMID- 14651414
TI  - A study of the feasibility of Internet administration of a computerized health
      survey: the headache impact test (HIT).
AB  - BACKGROUND: Headache impact test (HIT) is a precise, practical tool that
      quantifies the impact of headache on respondents' lives. It is the first widely
      available dynamic health assessment (DynHA). Applications of this brief, precise
      survey include population based screening for disabling headaches, tracking of
      individual patient scores over time, disease management programs and others. We
      use data from Internet HIT assessments during the fall of 2000 to (1) evaluate
      characteristics of respondents and assessments, (2) assess the utility of joint
      administration of HIT and the SF-8 Health Survey (SF-8) to screen for migraine
      and depression, and (3) explore associations between HIT scores and subsequent
      healthcare-related attitudes and behaviors. METHODS: We analyzed Internet HIT
      surveys completed between 9/1 and 11/30/2000 (n = 19,195). Subsamples include
      respondents who also completed (1) a 12-item Internet survey assessing severity,
      frequency, cause and management of headaches; (2) an e-mail survey measuring
      healthcare-related behaviors; (3) the SF-8; or (4) the website registration
      process, providing age and gender data. We used analysis of variance (ANOVA) to
      evaluate HIT score differences associated with age, gender, headache severity or
      frequency, and healthcare-related behaviors and attitudes and chi2 tests to
      assess the prevalence and comorbidity of migraine and depression. RESULTS: Three
      quarters of respondents achieved a precise HIT score in < or = 5 items. Most had
      moderate/severe headaches; 65% had headaches at least monthly. HIT scores were
      directly related to headache severity and frequency. Most respondents were
      females, with significantly higher HIT scores than males. Most HIT respondents
      were between ages 25 and 54 (HIT scores were higher for younger respondents).
      Sixty four percent screened positive for migraine; 20% for depression. Both
      conditions were more prevalent among females than males. Comorbid migraine and
      depression was 50% more prevalent among females and increased with age until age
      50. Patients with worse headache impact were more likely to seek care, discuss
      headaches with their providers and find HIT useful. CONCLUSIONS: It is feasible
      to use Internet-based dynamic assessments to measure health status. These data
      complement previous results showing that HIT differentiates respondents according
      to headache characteristics (severity and frequency). HIT plus SF-8 yields a
      practical screen for migraine and depression in headache patients and may lead to
      more effective treatment for patients with these conditions. Preliminary findings
      suggest that the experience of taking HIT on the Internet may motivate headache
      patients to seek care and discuss headaches with their providers.

PMID- 14651416
TI  - Translating the Short-Form Headache Impact Test (HIT-6) in 27 countries:
      methodological and conceptual issues.
AB  - The process of translating the Short-Form Headache Impact Test (HIT-6) in 27
      countries and the comparability of the content of the translations is discussed.
      HIT-6 translations were developed using a standard forward-backward translation
      process, including a cognitive debriefing step and international harmonization of
      the translations. Prior to translating the HIT-6, modifications were made to the
      English-language source form, to improve translation equivalence. In general, the
      HIT-6 was not difficult to translate. The most difficult items included
      colloquial expressions such as 'fed up' and words whose intended meaning changed
      in translation such as 'school' or 'lie down.' Subjects generally found the HIT-6
      translations to be clear and relevant. The translation process resulted in
      questionnaires that are both culturally appropriate and comparable in content.

PMID- 14651415
TI  - A six-item short-form survey for measuring headache impact: the HIT-6.
AB  - BACKGROUND: Migraine and other severe headaches can cause suffering and reduce
      functioning and productivity. Patients are the best source of information about
      such impact. OBJECTIVE: To develop a new short form (HIT-6) for assessing the
      impact of headaches that has broad content coverage but is brief as well as
      reliable and valid enough to use in screening and monitoring patients in clinical
      research and practice. METHODS: HIT-6 items were selected from an existing item
      pool of 54 items and from 35 items suggested by clinicians. Items were selected
      and modified based on content validity, item response theory (IRT) information
      functions, item internal consistency, distributions of scores, clinical validity,
      and linguistic analyses. The HIT-6 was evaluated in an Internet-based survey of
      headache sufferers (n = 1103) who were members of America Online (AOL). After 14
      days, 540 participated in a follow-up survey. RESULTS: HIT-6 covers six content
      categories represented in widely used surveys of headache impact. Internal
      consistency, alternate forms, and test-retest reliability estimates of HIT-6 were
      0.89, 0.90, and 0.80, respectively. Individual patient score confidence intervals
      (95%) of app. +/-5 were observed for 88% of all respondents. In tests of validity
      in discriminating across diagnostic and headache severity groups, relative
      validity (RV) coefficients of 0.82 and 1.00 were observed for HIT-6, in
      comparison with the Total Score. Patient-level classifications based in HIT-6
      were accurate 88.7% of the time at the recommended cut-off score for a
      probability of migraine diagnosis. HIT-6 was responsive to self-reported changes
      in headache impact. CONCLUSIONS: The IRT model estimated for a 'pool' of items
      from widely used measures of headache impact was useful in constructing an
      efficient, reliable, and valid 'static' short form (HIT-6) for use in screening
      and monitoring patient outcomes.

PMID- 14651417
TI  - Using item response theory to calibrate the Headache Impact Test (HIT) to the
      metric of traditional headache scales.
AB  - BACKGROUND: Item response theory (IRT) scoring of health status questionnaires
      offers many advantages. However, to ensure 'backwards comparability' and to
      facilitate interpretations of results, we need the ability to express the IRT
      score in the metrics of the traditional scales. OBJECTIVES: To develop procedures
      to calibrate IRT-based scores on the Headache Impact Test (HIT) into the metrics
      of the traditional headache scales. To assess the degree to which the calibrated
      HIT scores agree with the observed traditional scores and lead to the same
      conclusions in group comparisons. METHODS: We used telephone interview data (n =
      1016) and Internet data (n = 1103) from general population surveys of recent
      headache sufferers. Analyses were conducted in four steps: (1) develop IRT models
      for all items, (2) for each IRT score level, calculate the expected score on each
      of the traditional scales (calibration), (3) adjust this calibrated score for
      measurement error in the IRT score, (4) for each of the traditional scales,
      assess agreement between calibrated HIT scores and observed scores using
      intraclass correlation (ICC) and evaluate the agreement of mean scores and the
      relative validity (RV) in discriminating among groups differing in migraine
      diagnosis, headache severity, and change in impact over time. RESULTS: For the
      traditional categorical questionnaire items (the Migraine Specific Questionnaire
      (MSQ) and the Headache Disability Inventory (HDI)) the calibrated HIT agreed with
      the observed traditional scores: ICC's were between 0.80 and 0.94. In RV analyses
      the maximum mean difference between the observed and expected scores was 1.7
      points on a 0-100 scale for comparisons at one point in time. Analyses of change
      over time and analyses calibrating scores from the fixed-form HIT-6 to the metric
      of other questionnaires were also satisfactory although less precise. Analysis of
      non-standard questionnaire items (e.g. On how many days in the past 3 months did
      you have a headache, from the HIMQ and the MIDAS) required special IRT models.
      Agreement was less good: ICC's were between 0.56 and 0.61 and the maximum mean
      differences were 2.9 (on a 0-270 scale) and 3.8 (on a 0-450 scale) in RV analyses
      at one point in time. The ability of the calibrated scale scores to discriminate
      between groups was at least as good as the ability of the observed sum scales and
      often remarkably better. CONCLUSION: The theoretical advantage of IRT models in
      scale calibration is supported by our results. This approach to achieving
      comparability of new and widely-used scales and accelerating the accumulation of
      interpretation guidelines based on previous work warrant testing for measures of
      other generic and disease-specific concepts.

PMID- 14651418
TI  - Usefulness of the SF-8 Health Survey for comparing the impact of migraine and
      other conditions.
AB  - BACKGROUND: Migraine headaches have been shown to have substantial personal and
      societal implications. Health-related quality of life (HRQOL) assessments of
      migraineurs have been used to monitor and evaluate patient- and population-based
      outcomes, and to evaluate effectiveness and responsiveness to treatment. In this
      paper, we test a new, even shorter generic health survey, the SF-8 Health Survey
      (SF-8), an alternate form that uses one question to measure each of the eight SF
      36 Health Survey (SF-36) domains, in a sub-sample of migraine sufferers. METHODS:
      Data from 7557 participants surveyed via the Internet and mail were used to
      document the burden of migraine on HRQOL and to compare the relative burden of
      migraine with other chronic conditions using the SF-8. RESULTS: Migraineurs'
      HRQOL is similar to those with congestive heart failure, hypertension and
      diabetes, and is better than those with depression. Migraine sufferers experience
      better physical health and worse mental health (MH) than those with
      osteoarthritis. Results support prior research indicating that the burden of
      migraine on functional health and well-being is considerable and comparable to
      other chronic conditions known to have substantial impact on HRQOL. CONCLUSIONS:
      The SF-8 may provide a more practical and efficient method to describe the burden
      of migraine in population studies.

PMID- 14651419
TI  - Evaluation of quality of life in a clinical trial with nonrandom dropout: the
      effect of epoetin alfa in anemic cancer patients.
AB  - Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of
      anemic cancer patients treated with nonplatinum-containing chemotherapy who
      received epoetin alfa or placebo were subjected to a sensitivity analysis. Three
      QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia
      (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study
      Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis
      were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An
      fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the
      SF-36 physical and mental component summary scales. Lower QOL scores were
      reported for patients who discontinued early, suggesting a nonrandom dropout
      process. Significant correlations (ranging from 0.37 to 0.77) between individual
      rates of change and the time to early termination of therapy or death supported
      this conclusion. Estimates of within-treatment-arm QOL change over time are more
      conservative with the missing not at random (MNAR) assumption as compared with
      the more optimistic estimates with the assumption that missing QOL data are
      missing at random (MAR). However, the between-treatment-arm comparisons were
      consistent across analyses, demonstrating statistically significant differences
      in favor of the epoetin alfa arm for four of the seven outcome measures.

PMID- 14651420
TI  - Do differences in methods for constructing SF-36 physical and mental health
      summary measures change their associations with chronic medical conditions and
      utilization?
AB  - BACKGROUND AND OBJECTIVE: Various approaches have been employed to derive
      physical health and mental health summary scores for the SF-36 and the RAND-36,
      but head-to-head comparisons of alternative scoring algorithms are rare. We
      determined whether the associations of the physical and mental health summary
      scores with chronic medical conditions and utilization would differ depending on
      the scoring algorithm used. METHODS: We examined 5701 patients receiving medical
      care from an independent association of 48 physician groups located primarily in
      the western United States and compared SF-36 and RAND-36 scoring of physical
      health and mental health summary scores. Associations with the presence of
      diabetes, heart disease, and kidney disease, as well as with utilization of
      medical care and mental health care were compared using bivariate and
      multivariate analysis. To examine the relationship between SF-36 and RAND-36
      scores, we regressed the SF-36 physical and mental health composite scores on the
      RAND-36 physical and mental health summary measures and vice versa. RESULTS: We
      found that the SF-36 and RAND-36 summary scores generally yielded results similar
      to one another across measures of heart disease, diabetes, and kidney disease, as
      well as measures of utilization. However, for each chronic medical condition, the
      RAND-36 showed a slightly larger decrement in mental health than did the SF-36.
      CONCLUSIONS: Differences between the two sets of summary scores were consistent
      with their respective conceptual and analytic approaches. Where comparisons of
      results between the SF-36 and RAND-36 summary scores are desirable in future
      studies, they can be estimated using the regression equations derived in this
      study.

PMID- 14651421
TI  - Quality of life of HIV-infected patients: psychometric properties and validation
      of the German version of the MQOL-HIV.
AB  - OBJECTIVE: To determine the psychometric properties of the recently developed
      German version of the Multidimensional Quality of Life Questionnaire for HIV/AIDS
      (MQOL-HIV) and to test its performance in a sample of HIV-infected patients.
      METHODS: Two-hundred and seven outpatients with HIV/AIDS were interviewed with
      the German version of the MQOL-HIV; 109 patients were interviewed a second time
      approximately 2 weeks later. Patients also completed the Beck Depression
      Inventory (BDI) and the World Health Organization Disability Assessment Schedule
      II (WHODAS II). RESULTS: The German version of the MQOL-HIV showed satisfactory
      internal consistency (r: 0.74-0.85, sexual functioning: r = 0.61) and test-retest
      reliability in most subscales (r: 0.74-0.89, medical care: r = 0.67). Convergent
      validity with WHO-DAS II and BDI was satisfactory for most domains. Exploratory
      factor analysis yielded a seven-factor solution with separate factors for
      physical, emotional, cognitive, social and financial aspects, sexual functioning
      and medical care. CD4 count and source of infection were associated with most QOL
      domains, whereas age and gender showed no major impact on QOL. High rates of
      missing values were seen in the partnership domain and substantial ceiling
      effects in the area of medical care. CONCLUSIONS: Overall the German version of
      the MQOL-HIV showed satisfactory reliability and validity. However, the domains
      of partnership, sexuality and medical care should generally receive more emphasis
      in future research on QOL assessment in patients with HIV/AIDS and the MQOL-HIV
      may be improved in these domains.

PMID- 14651422
TI  - Reliability and validity of the SF-36 in HIV-infected homeless and marginally
      housed individuals.
AB  - OBJECTIVE: To assess the reliability and validity of the Short-Form 36 (SF-36)
      health survey as a health status indicator among HIV-infected homeless and
      marginally housed (HMH) individuals. METHODS: Between July 1996 and May 2000, a
      sample of HMH individuals completed interviews that included the SF-36. Responses
      to the SF-36 were analyzed for missing data, range, internal consistency, and
      construct validity. RESULTS: Among 330 individuals interviewed, 83% were male,
      43% were African-American, and the median age was 39 years. All internal
      consistency reliability coefficients exceeded 0.70, all item-scale correlations
      exceeded 0.40, all items were more strongly correlated with their hypothesized
      scale than any other scale, and all reliability coefficients exceeded inter-scale
      correlations for the same scale. Three of four physical health scales were
      significantly associated with CD4 cell count and HIV viral load. All scales were
      significantly associated with depression. DISCUSSION: We found that scales were
      internally consistent, items correlated to an acceptable degree with their
      hypothesized scales, items were distinct from other scales, physical scales were
      associated with CD4 cell count and viral load, and all scales were associated
      with depression. These analyses provide evidence for the reliability and validity
      of the SF-36 as a measure of health status in HIV-positive HMH individuals.

PMID- 14651423
TI  - Areas of decrement in health-related quality of life (HRQL): comparing the SF-12,
      EQ-5D, and HUI 3.
AB  - BACKGROUND: Different measures of health status and health-related quality of
      life (HRQL) have been advocated for different purposes at the clinical and
      population level. Relatively little is known about how these measures function in
      relationship to one another. We examined the relationship between the Short-Form
      12 (SF-12), EQ-5D, and Health Utilities Index (HUI) Mark 3 for overall scores and
      in analogous domains of health. A convenience sample was obtained through
      surveying patients at an inner-city community health center. MEASUREMENTS AND
      MAIN RESULTS: The sample was comprised primarily of low-income racial/ethnic
      minorities; 393 patients were approached and 301 patients (77%) participated. The
      three measures had correlations between overall scores that ranged from 0.41 to
      0.69 and correlations between similar domains from different measures that ranged
      from 0.42 to 0.59. For the HUI 3, 'any' impairment most frequently was noted with
      pain, vision, cognition, and emotion. For the EQ-5D, pain/discomfort and
      anxiety/depression were reported as impaired most often. Compared to published
      population scores, participants reported impairments with increased frequency and
      at a greater level. CONCLUSIONS: Participants demonstrated consistency with
      responses to similar types of items and correlations between related aspects of
      health were moderate to strong. Domains of health most often reported as impaired
      resembled those noted in national surveys. Despite differences in the structure
      of the measures, all three instruments capture information about decrements in
      broadly analogous domains of health.

PMID- 14651424
TI  - Responsiveness of the EuroQol (EQ 5-D) and the SF-36 in elderly patients with
      displaced femoral neck fractures.
AB  - OBJECTIVES: To evaluate the responsiveness of the EuroQol (EQ-5D) and Short-Form
      36 (SF-36) instruments, i.e. their ability to capture clinically important
      changes, in elderly patients with a displaced femoral neck fracture. The study
      was part of a prospective randomised study comparing two different surgical
      procedures, internal fixation (IF) and total hip replacement (THP). SETTING:
      University hospital. PATIENTS: A total of 110 patients, mean age 80 years with an
      acute displaced femoral neck fracture (Garden III and IV). The inclusion criteria
      were age > or = 70, absence of severe cognitive dysfunction, independent living
      status and independent walking capability. INTERVENTION: The patients were
      randomised to IF or to a THR. MAIN OUTCOME MEASUREMENTS: Health-related quality
      of life according to EQ-5D and SF-36. Responsiveness measured by the ability of
      the EQ-5D and the SF-36 to detect clinically relevant differences in the study
      population according to an external criterion (EC) for outcome (good or less good
      clinical outcome). Responsiveness was measured in terms of change scores,
      standardised effect size (SES) and standardised response mean (SRM). RESULTS: The
      rated prefracture EQ-5D(index) scores and SF-36 scores showed good correspondence
      with the scores of age-matched Swedish reference populations. The relationship
      between the EC and EQ-5D(index) score and the SF-36 global score showed
      significant differences in both comparisons (p < 0.001). The responsiveness
      expressed with the SES and SRM were large for both the EQ-5D (1.37 and 0.90,
      respectively) and for the SF-36 global score (0.89 and 0.82, respectively). The
      correlation between the change scores for the SF-36 global score and the EQ-5D
      was 0.39 (p < 0.001). CONCLUSION: The results showed high responsiveness for both
      the EQ-5D and the SF-36, indicating that both instruments are suitable for use as
      outcome measures in clinical trials in elderly hip fracture patients.

PMID- 14651425
TI  - The effect of different methods of collecting data: mail, telephone and filter
      data collection issues in utility measurement.
AB  - When collecting data researchers can interview participants, conduct telephone
      interviews, or mailout questionnaires. Often mixed methods are used. Whether
      these methods produce equivalent data is under-researched in the health-related
      quality of life (HRQoL) field. In addition, the effect of using filter questions
      has not been researched among HRQoL multi-attribute utility instruments. This
      study randomly sampled from Melbourne, Australia, and employed a test-retest
      design to investigate whether mail or telephone interview made any difference to
      Assessment of Quality of Life (AQoL) instrument utility scores. A filter question
      AQoL version investigated the effect of filters on scores. There was no
      significant difference in standard AQoL scores between mail self-completion and
      telephone interview, regardless of which was administered first. Inclusion of
      filter questions encouraged respondents to select the best response category
      thereby screening out minor health conditions. The effect was to increase utility
      scores by 0.06 or 7%. This effect has not been previously reported in utility
      instruments and has profound implications for economic evaluations using cost
      utility analysis; there are implications for researchers using filter questions
      in general. In conclusion, researchers should feel confident that utility scores
      elicited from the standard AQoL through self-completion mail and telephone
      interview administrations are directly comparable.

PMID- 14651426
TI  - Quality of life of patients with type I diabetes mellitus.
AB  - The objective of this study was to assess health related quality of life (QOL) in
      patients with type I diabetes mellitus (DMT1) and to compare their QOL with the
      QOL of persons of comparable age in the general population. Furthermore we wanted
      to investigate which factors mostly influence QOL. In a Dutch cohort of 281
      patients with DMT1 QOL was assessed using two generic instruments: the EuroQol
      and the RAND-36. We performed regression analyses to investigate relationships
      between several demographic (e.g. sex, age, marital status) and diabetes-specific
      variables (e.g. HbA1c, frequency of insulin injection, presence of acute and
      chronic complications) and QOL. The Spearman rank correlations between RAND-36
      domains and EuroQol were analysed. RAND-36 results showed, for almost all
      domains, a QOL comparable with persons of comparable age in the general
      population. In contrast the QOL measured with the EuroQol was lower for subjects
      with DMT1. Hyperglycaemic complaints and macrovascular complications had a
      profound negative influence on QOL. Most correlations between the RAND-36 results
      and the EuroQol results corresponded with our expectations. Longitudinal data and
      comparison with results of several diabetes-specific questionnaires should help
      to establish which instrument might be most appropriate to measure QOL in
      patients with DMT1.

PMID- 14651427
TI  - Life satisfaction in patients with chest pain subsequently diagnosed as coronary
      heart disease--connection through depressive symptoms?
AB  - The aim of this study was to investigate factors associated with life
      dissatisfaction in symptomatic patients (n = 144) with chest pain subsequently
      diagnosed as coronary heart disease (CHD) by coronary angiography. Life
      dissatisfaction was assessed with a four-item life satisfaction scale (LS),
      depression with the 21-item Beck Depression Inventory (BDI) and other psychiatric
      symptoms with the symptom check list (SCL). DSM-III-R Axis I and Axis II
      psychiatric diagnoses were performed by means of the Structured Clinical
      Interview. All assessments took place one day before angiography. Twenty-four per
      cent of CHD patients were dissatisfied with their lives. Life dissatisfaction was
      associated with being unmarried. Dissatisfied patients had Axis I mental
      disorders and Axis II personality disorders more frequently than others.
      Psychiatric and depressive symptoms according to the SCL and BDI, respectively,
      were also higher among dissatisfied patients. In multiple logistic regression
      analyses, mental disorders were related to life dissatisfaction when age, sex,
      employment status, New York Heart Association class, duration of chest pain
      symptoms and work load were controlled in the model. Married subjects had a lower
      probability of being dissatisfied with their lives than other subjects (Odds
      Ratio, OR: 0.23). When BDI scores were included in the model, the only factor
      independently associated with life dissatisfaction was the severity of depressive
      symptoms (OR: 1.81). To conclude, life dissatisfaction is not primarily
      determined by the severity of CHD but by the existence of depressive symptoms.

PMID- 14651428
TI  - Quality of life terminology included in package inserts for US approved
      medications.
AB  - OBJECTIVES: To identify and review prescription drugs approved in the US
      containing quality of life (QoL) terminology within the package inserts (PIs).
      METHODS: The electronic Physician Desk Reference (PDR) was searched for the
      terminology 'Quality of Life' or 'QoL' as of December 2000. Summary basis of
      approvals (SBAs) served as the primary data sources were retrieved. The two
      categories evaluated within the SBAs were QoL components (year submitted, trials,
      efficacy, statistics, type of submission) and QoL instruments utilized within
      clinical studies. RESULTS: Eighteen medications comprising 20 indications with
      QoL claims were documented in the PIs. The first approved QoL claim was submitted
      in 1989 and the most recent was in 1998. Eight (40%) of the drug indications had
      QoL measures included in two trials. One quarter of the PI listings used QoL
      measures as primary efficacy endpoints. Many sponsors provided detailed
      information on the types or categories of QoL data collected. CONCLUSION: Many
      drug development programs incorporate QoL measures into clinical studies however
      only a few are accepted into the PI. Despite this study finding, the increased
      interest in assessing the value and full impact of new therapies has led to
      greater inclusion of all types of patient assessments in clinical trials.

PMID- 14651429
TI  - The Caregiver Quality of Life Cystic Fibrosis (CQOLCF) scale: modification and
      validation of an instrument to measure quality of life in cystic fibrosis family
      caregivers.
AB  - OBJECTIVE: Modify the Caregiver Quality of Life Index-Cancer (CQOLC) scale
      (Weitzner, Jacobsen et al. Qual Life Res 2000; 8: 55-63) as the Caregiver Quality
      of Life Cystic Fibrosis (CQOLCF) scale, validate it with cystic fibrosis (CF)
      family caregivers, and assess caregiver quality of life QOL with patient disease
      severity. METHODS: Following modifications, 100 family caregivers were
      administered the CQOLCF. Construct validity was assessed by the Medical Outcomes
      Study Short Form (SF-36) and the Beck Depression Inventory (BDI). Pulmonary
      function scores and hospitalizations assessed relationship between caregiver QOL
      and patient disease severity. RESULTS: Split-half reliability was 0.862 and
      internal consistency (Cronbach's alpha) was 0.909. As expected, there were
      relatively high correlations with the mental health (0.634) and emotional
      distress (-0.687); and low correlations with physical health (0.049). ANCOVA
      examined differences in the CQOLCF totals based on disease severity, controlling
      for age. Significant mean differences existed (days hospitalized F = 3.010, sig.
      = 0.022). DISCUSSION: The CQOLCF appears to be a valid, reliable, and internally
      consistent disease-specific scale with CF family caregivers. Future research
      recommendations include administering the CQOLCF to an increased study sample to
      explore item factor analysis.

PMID- 14651430
TI  - Internal consistency and validity of the Stroke Impact Scale 2.0 (SIS 2.0) and
      SIS-16 in an Australian sample.
AB  - BACKGROUND AND PURPOSE: The impact of stroke is multidimensional however standard
      stroke measures do not discriminate well when stroke patients are less physically
      impaired. The Stroke Impact Scale 2.0 (SIS 2.0) is a multidimensional measure of
      the impact of stroke but its' psychometric properties require further testing.
      The SIS-16 is a measure of physical functioning designed to be more sensitive to
      differences in physical functioning than current stroke outcome measures but
      there is only preliminary information detailing its' reliability and validity.
      The current study examined the internal consistency and validity of the SIS 2.0
      and SIS-16 in an Australian sample of stroke patients. METHODS: The SIS 2.0, SIS
      16, World Health Organization Bref-Scale (WHOQOL-BREF) and Zung's Self-Rating
      Depression Scale (SDS) were completed by 74 stroke patients in rural Victoria,
      Australia. RESULTS: The item convergent validity index indicated good item
      convergence of the SIS-16 and SIS 2.0 domains. The item discriminant validity
      index had only adequate divergence for most SIS 2.0 domains. Internal
      consistencies of the SIS-16 and SIS 2.0 domains were acceptable (alpha = 0.87
      0.95). Correlations between the SIS-16 and SIS 2.0 and the WHOQOL-BREF and SDS
      supported the convergent and discriminant validity of the SIS-16 and all the
      dimensions of the SIS 2.0 except 'Participation' which lacked discriminant
      validity. CONCLUSIONS: The SIS 2.0 and SIS-16 had good psychometric properties
      with support for the internal consistency and validity of both measures.

PMID- 14651431
TI  - Validity and reliability of the Italian translation of the MOS-HIV health survey
      in persons with AIDS.
AB  - OBJECTIVES: To evaluate the validity and reliability of the Italian version of
      the 35-item Medical Outcome Study HIV Health Survey (MOS-HIV) when applied to
      persons with AIDS. METHODS: The study population consisted of 185 adults with
      AIDS residing in Rome and participating in a randomised controlled trial on home
      care. Diagnosis was made between 1 October 1994 and 1 April 1996, and enrollment
      took place within 2 months of diagnosis. The MOS-HIV, which measures 10
      dimensions of health-related quality of life (QoL), was administered at baseline
      and every 3 months thereafter during the 1-year follow-up. Tests of convergent
      and concurrent construct validity were conducted for all scales. RESULTS: Of the
      185 trial participants, 146 responded to the questionnaire; 82 responded at least
      twice (including baseline collection) during follow-up. For the role functioning,
      general health, and vitality scales, the distribution of scale scores was
      concentrated at the lower half of the range. Internal consistency reliability was
      adequate (>0.80) for all scales. Baseline scores tended to increase with
      decreasing AIDS severity and with increasing age. There were improvements over
      time in the role functioning, vitality, and health distress scales. CONCLUSIONS:
      The MOS-HIV had good reliability among persons with AIDS. There was a moderate
      floor effect for some of the subscales. Tests of convergent and construct
      validity were generally confirmed. Additional studies are needed to evaluate the
      responsiveness to changes over time.

PMID- 14651432
TI  - The doctor's duty to the elderly patient in clinical trials.
AB  - The ethical principles of beneficence (or non-maleficence), respect for persons
      and justice apply to both good medical practice and clinical research. Doctors
      have a duty to offer to their patients, of all ages, the opportunity to take part
      in clinical trials and to ensure that research is appropriately designed and
      conducted. Barriers to participation of elderly patients in clinical trials
      include complex protocols with onerous outcome measures, a research focus on
      aggressive therapies with substantial toxicity, restrictive entry criteria
      unnecessarily excluding concurrent conditions and medication, patients' and
      families' limited expectations of benefits and lack of financial, logistic and
      social support.Participation is encouraged when attitudes of care staff towards
      research are positive, altruistic motives are acknowledged, approval of family
      members is gained and protocols are designed for patient rather than staff
      convenience. Special consideration should be given to ensuring that patient
      consent is fully informed and freely given. Elderly patients may have more
      difficulty comprehending consent information and particular attention should be
      given to compensating for communication and sensory deficits, improving
      readability of information sheets and consent forms, and considering the use of
      innovative consent procedures. Those with cognitive impairment and the
      institutionalised are vulnerable to exploitation and require special
      consideration and management.

PMID- 14651433
TI  - Long-acting injectable antipsychotics in the elderly: guidelines for effective
      use.
AB  - The elderly are at increased risk for psychosis because of age-related
      deterioration of cortical areas and neurochemical changes, comorbid physical
      illnesses, social isolation, sensory deficits and polypharmacy. The prevalence of
      psychiatric and neuropsychiatric disorders requiring treatment with an
      antipsychotic agent is expected to increase dramatically among people aged >64
      years. Antipsychotic agents are effective in the treatment of schizophrenia,
      schizoaffective disorder, behavioural symptoms in patients with dementia, and
      mood disorders with psychosis. However, failure to adhere to a prescribed
      medication regimen by patients with psychosis is one of the most frustrating
      problems faced by mental healthcare providers, because of the high risk of
      relapse associated with partial compliance. For patients with psychosis who will
      not or cannot take oral medications on a regular daily basis or have other
      characteristics, such as memory, vision or auditory impairment, which contribute
      to partial compliance, long-acting injectable antipsychotic medication offers a
      solution. Older patients are especially at risk of adverse effects associated
      with traditional antipsychotic agents, such as motor effects, postural
      hypotension, excessive sedation, and anticholinergic effects because of age
      related pharmacokinetic and pharmacodynamic factors, coexisting medical illnesses
      and concomitant medications. Therefore, drug dosage recommendations in the
      elderly are much more conservative than in younger patients. The appropriate
      starting dose of an antipsychotic in older individuals is 25% of the usual adult
      dose; total daily maintenance doses ranges from 25-50% of the adult dose. There
      are few studies regarding the use of depot antipsychotics in elderly patients.
      Studies that are available indicate that traditional antipsychotic agents given
      as depot injections are associated with positive outcomes in the elderly. Because
      the risks for extrapyramidal symptoms and tardive dyskinesia are reduced
      dramatically with atypical antipsychotics compared with traditional agents, the
      development of long-acting atypical antipsychotic formulations has been pursued.
      Of the atypical antipsychotics, risperidone is the first agent to be approved in
      a long-acting injectable formulation. Unpublished clinical data have revealed
      that patients treated with long-acting injectable risperidone (25mg, 50mg or
      75mg) are more likely to show significant clinical improvement than placebo. In
      addition, hospitalisation rates decreased continuously and significantly during 1
      year of treatment for patients who received long-acting injectable
      risperidone.Long-acting injectable antipsychotic medication should be considered
      for older patients for whom long-term treatment is indicated. The choice of which
      drug to use should be based on patients' history of response and personal
      preference, clinician's previous experience and pharmacokinetic properties.

PMID- 14651436
TI  - Donepezil in vascular dementia: a viewpoint by David S. Geldmacher.

PMID- 14651435
TI  - Donepezil: in vascular dementia.
AB  - Vascular dementia (VaD), caused by stroke or small vessel disease, is the second
      most common form of dementia after Alzheimer's disease (AD). Donepezil, an
      acetylcholinesterase inhibitor currently indicated for use in patients with mild
      to moderate AD, has recently been evaluated in VaD. Donepezil 5 or 10mg once
      daily provided significant improvements in cognition, as determined by the
      Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), relative to
      placebo, after 24 weeks in patients with VaD. Pooled data from two, randomised,
      double-blind, phase III trials showed that the least-squares mean change from
      baseline score effect size for the ADAS-cog was -1.79 for donepezil 5mg once
      daily (p < 0.001) and -2.28 for donepezil 10mg once daily (p < 0.001) at 24 weeks
      (observed cases). Significant improvement in global functioning occurred with
      donepezil 5mg once daily compared with placebo (p = 0.003), but not with
      donepezil 10mg once daily, as measured by the Clinician's Interview-Based
      Impression of Change-plus version score (pooled data, observed cases). Donepezil
      was generally well tolerated in patients with VaD. Most adverse events were mild
      to moderate in nature, with diarrhoea and nausea being the most common.

PMID- 14651434
TI  - Chronic prostatitis/chronic pelvic pain syndrome in elderly men: toward better
      understanding and treatment.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common of
      the prostatitis syndromes. It is characterised by pelvic pain, with or without
      voiding symptoms. CP/CPPS accounts for 2 million office visits in the US alone.
      Recent epidemiological studies have shown that CP/CPPS can affect men at any age,
      including those in their 80s. The aetiology is unknown but proposals include
      infectious, autoimmune, neurologic and psychiatric causes. Men with CP/CPPS are
      much more likely to have had a past medical history of cardiovascular,
      neurologic, psychiatric or infectious disease (particularly sinusitis) as
      compared with asymptomatic individuals. Although leucocytes are commonly found in
      the prostatic fluid of these men, they do not correlate with the symptoms. The
      clinical evaluation now includes a validated, self administered symptom score,
      the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI),
      which was designed as an outcome measure for treatment trials. This can aid in
      diagnosis and follow-up of patients' response to therapy. Treatment for CP/CPPS
      is empiric and limited by a lack of randomised, placebo-controlled clinical
      trials. Antimicrobials are commonly used to treat the symptoms of CP/CPPS.
      However, the finding that asymptomatic men have equal or greater numbers of
      bacteria which localise to the prostatic fluid, compared with men with CP/CPPS,
      has raised doubts about the contribution of infection to the symptoms. Other
      commonly used drugs include alpha-adrenoceptor antagonists, anti-inflammatory
      drugs, tricyclic antidepressants and anticholinergic agents. The adverse effects
      of these medications are a concern in older men with CP/CPPS. Other therapies
      available include minimally invasive procedures such as microwave thermotherapy
      and transurethral needle ablation, and now neuromodulation devices.Although much
      progress has been made, particularly in the last 7 years, considerable work still
      remains to be done to determine the aetiology and pathogenesis of CP/CPPS, and to
      develop mechanism based therapy that is shown to be effective in controlled
      trials.

PMID- 14651437
TI  - Donepezil in vascular dementia: a viewpoint by Gustavo C. Roman.

PMID- 14651438
TI  - Donepezil in vascular dementia: a viewpoint by Sandra E. Black.

PMID- 14651439
TI  - Galantamine vs donepezil in the treatment of Alzheimer's disease.

PMID- 14651441
TI  - Allergen prick-puncture skin testing in the elderly.
AB  - Many older patients present with rhinitis, conjunctivitis, asthma or itching that
      the patient attributes to allergies. Yet physicians often dismiss allergy in the
      elderly as irrelevant. Testing elderly patients for allergies is sometimes
      challenging as changes in the skin may cause difficulty in applying skin tests,
      and the response of the skin may be difficult to measure. The prick puncture skin
      test is the preferred method of immediate-type allergy testing, but careful
      examination of the skin prior to skin testing is important. If the area of skin
      where allergen skin tests are routinely placed is either atrophic or severely sun
      damaged, a sun-protected area should be sought. If no suitable area of skin can
      be identified, in vitro allergen testing should be considered. Skin-test results
      must be interpreted with care in the elderly. Positive skin tests to an allergen
      must correlate with a history of exacerbation to the allergen. By identifying
      specific allergens to which the elderly patient is sensitive, avoidance measures
      or specific allergen vaccination can be recommended, improving the quality of
      life and decreasing the need for medications.

PMID- 14651443
TI  - Gabapentin for the treatment of behavioural alterations in dementia: preliminary
      15-month investigation.
AB  - BACKGROUND: Although the core feature of dementia is progressive cognitive
      disruption, non-cognitive behavioural problems are expressed in most patients
      with dementia during the course of their illness. While psychotropic drugs are
      frequently used to control behavioural symptoms, comorbidities, which are very
      common in the geriatric population, could often limit their use. Gabapentin may
      be a potential treatment in such situations. METHODS: In this open, baseline
      comparison study 20 patients with probable Alzheimer's disease with behavioural
      alterations and serious comorbidities (paralytic ileus, open-angle glaucoma,
      ischaemic cardiopathy, hepatic failure or severe prostatic hyperplasia) received
      gabapentin for 15 months. Patients were allowed to continue any previous therapy
      for concurrent diseases. However, concomitant antipsychotic or benzodiazepine
      intake was not permitted. RESULTS: Gabapentin appeared to be efficacious and well
      tolerated in this patient population, and did not appear to interact with other
      drugs. General benefit is reflected by a reduction of caregiver stress. No
      patients withdrew before the end of the study and no serious adverse events were
      reported. CONCLUSION: The results of this study in patients with probable
      Alzheimer's disease with behavioural alterations and serious comorbidities
      indicate that gabapentin provides significant and sustained efficacy in terms of
      behaviour, with associated reductions in caregiver burden. The results of an
      ongoing larger, randomised, double-blind study of gabapentin are keenly awaited
      and may help to provide a safer and more efficacious treatment option for this
      group of patients.

PMID- 14651442
TI  - Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly
      patients.
AB  - Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease,
      severe diarrhoea and gastric acid hypersecretion associated with an islet-cell
      tumour of the pancreas (gastrinoma). The true incidence and prevalence of this
      rare disease is unknown; in the US, the frequency is one per one million people
      and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome
      is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple
      endocrine neoplasia type 1 (MEN 1). The diagnosis of Zollinger-Ellison syndrome
      is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is
      >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised
      patients, or when this hypergastrinemia is associated with a pH <2. The treatment
      is based on control of gastric acid hypersecretion and of the malignant tumour
      and its possible metastases. Proton pump inhibitors are the most effective
      antisecretory drugs and can be administered in the elderly at high dosages
      without drug-related adverse effects. As an initial therapy, daily dosages of
      omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term
      treatment the doses can be greatly reduced once effective control of the gastric
      output has been established. Intravenous proton pump inhibitors may be
      administered when patients cannot take oral therapy, particularly in acute
      conditions. All sporadic localised gastrinomas should be excised if possible.
      When liver metastases are also present, their debulking may improve symptoms and
      survival, and facilitate medical treatment. There is some controversy as to the
      surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues
      can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric
      enterochromaffin-like (ECL) cells and can thus contribute to treating the disease
      more effectively. Their antiproliferative effect can be used in treating liver
      metastases. Chemotherapy is not the therapy of choice in patients with
      gastrinomas and is indicated only in those with malignant progressive disease;
      interferon alpha, embolisation and chemoembolisation are not advisable for the
      elderly. The treatment of elderly Zollinger-Ellison syndrome patients, similarly
      to all elderly oncological patients, should be based on the use of comprehensive
      geriatric assessment. This will enable the clinician to define the functional
      status of the elderly person, to decide whether the patient can tolerate surgery
      and/or the stress of antineoplastic therapy, and finally, to determine whether
      this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome
      or whether the only possible choice is palliative relief of symptoms.

PMID- 14651444
TI  - Glucosamine: a review of its use in the management of osteoarthritis.
AB  - Glucosamine occurs naturally in all human tissues. It stimulates the synthesis of
      glycosaminoglycan, proteoglycan and hyaluronic acid, although the precise
      mechanism of action remains to be established. Formulated as glucosamine sulphate
      (Dona) and various others), glucosamine has been evaluated for its efficacy in
      relieving the symptoms of osteoarthritis and its disease-modifying potential. In
      two large randomised, double-blind, multicentre studies in patients with
      osteoarthritis, oral or intramuscular glucosamine for 4-6 weeks was associated
      with a greater decrease in symptom severity (as assessed by the Lequesne index)
      than placebo. In addition, there was a greater proportion of responders (defined
      as patients with a >or=3-point reduction in the Lequesne index, along with a
      positive overall assessment by the investigator) at the end of the treatment
      period with glucosamine than with placebo. In two large 4-week trials, oral
      glucosamine produced similar improvements to ibuprofen in the Lequesne index in
      one study and in articular pain scores in the other study. In a smaller 8-week
      comparative trial, oral glucosamine therapy achieved a significantly greater
      improvement in articular pain score than ibuprofen, and the investigators rated
      treatment efficacy as 'good' in a significantly greater proportion of glucosamine
      than ibuprofen recipients. In comparison with piroxicam, glucosamine
      significantly improved arthritic symptoms after 12 weeks of therapy and remained
      effective 8 weeks after treatment was discontinued. Beneficial effects of long
      term oral glucosamine therapy in preventing joint space narrowing and improving
      symptoms were shown in two 3-year placebo-controlled trials in a total of 414
      patients with osteoarthritis. Statistically significant differences favouring
      glucosamine were noted in the per-protocol and intention-to-treat analyses for
      the primary endpoints for both joint structural changes and symptom modification.
      Glucosamine has a tolerability profile similar to that of placebo and is better
      tolerated than ibuprofen or piroxicam. In particular, glucosamine recipients had
      a markedly lower incidence of gastrointestinal disturbances than those receiving
      ibuprofen. Other adverse events reported in both glucosamine and ibuprofen
      recipients were pruritus or skin reactions, flushing and fatigue. In general, a
      lower incidence of withdrawal from clinical trials was reported for glucosamine
      recipients than either ibuprofen or piroxicam recipients. CONCLUSION: In short
      term clinical trials, glucosamine provided effective symptomatic relief for
      patients with osteoarthritis of the knee. In addition, glucosamine has shown
      promising results in modifying the progression of arthritis over a 3-year period.
      Glucosamine may therefore prove to be a useful treatment option for
      osteoarthritis.

PMID- 14651446
TI  - Trisomy 16 in a pigtailed macaque (M. nemestrina) with multiple anomalies and
      developmental delays.
AB  - A female pigtailed macaque (Macaca nemestrina) with unusual physical
      characteristics, deficits in learning and cognitive tasks, abnormal social
      behavior, and abnormal reflexes and motor control was followed from birth until 3
      years of age and found to have trisomy 16, which is homologous to trisomy 13 in
      humans. The animal described here showed similar features to cases of trisomy 16
      and 18 (human trisomy 13 and 18, respectively) reported previously in nonhuman
      primates. However, both significant differences and similarities were found when
      compared with the homologous human trisomy. Evaluation of the genetic components
      of these disorders as well as systematic developmental evaluation can lead to new
      insights into the genetic basis of speciation, development, and the underlying
      differences between humans and their closest living relatives.

PMID- 14651448
TI  - The Willowbrook futures project: a longitudinal analysis of person-centered
      planning.
AB  - We conducted a longitudinal comparative evaluation of person-centered planning
      processes and outcomes for 20 individuals with intellectual disabilities and
      problem behavior (former residents of Willowbrook) and a matched contrast group,
      who received traditional interdisciplinary service planning (ISP). At the
      inception of the study, all participants were living in one of four other
      developmental centers (institutions) in New York City. Process and outcome data
      obtained from questionnaires completed by team members approximately every 8
      months at four time periods showed that the rate of improvement in both person
      centered planning process and outcomes for the intervention group was
      significantly greater than that of the comparison group. Eighteen of 19 person
      centered planning participants moved to community living arrangements, as did 5
      of 18 in the contrast group.

PMID- 14651449
TI  - Positive perceptions held by support staff in community mental retardation
      services.
AB  - Existing research on support staff has been focused on variables associated with
      stress. However, there has been little attention to the possibility that staff
      may also experience a number of positive outcomes or perceptions. In the present
      study, 101 support staff working with adults who had mental retardation completed
      measures of burnout and mental health and a new measure: the Staff Positive
      Contributions Questionnaire (SPCQ). A range of positive perceptions of their work
      was endorsed by participants, demonstrating that such perceptions do exist and
      require theoretical explanation. The SPCQ had promising internal consistency,
      test-retest reliability, and construct validity. Thus, further research with this
      instrument is warranted.

PMID- 14651445
TI  - Pravastatin: a review of its use in elderly patients.
AB  - Pravastatin (Pravachol) is a competitive, reversible HMG-CoA reductase inhibitor
      that lowers serum cholesterol levels by inhibiting de novo cholesterol synthesis
      and has antiatherogenic effects that appear to be partially independent of its
      lipid-lowering effects. Pravastatin 10-40 mg/day produced significant reductions
      (vs baseline or placebo) in serum total cholesterol (TC) and low-density
      lipoprotein cholesterol (LDL-C) levels in elderly patients (aged >or=60 or >or=
      65 years) with hypercholesterolaemia or normal cholesterol levels. Serum
      triglyceride and high-density lipoprotein cholesterol levels also improved in
      some studies, but not in others. Coadministration of cholestyramine, another
      lipid-lowering agent, further enhanced the lipid-lowering effects of pravastatin
      in elderly patients. Data from the large, long-term (3-6 years) PROspective Study
      Of Pravastatin in the Elderly at Risk (PROSPER), Cholesterol And Recurrent Events
      trial (CARE) and Long term Intervention with Pravastatin in Ischaemic Disease
      (LIPID) trials demonstrated that pravastatin 40 mg/day reduces coronary events in
      elderly patients with hypercholesterolaemia or normal cholesterol levels, with or
      at high risk of developing coronary heart disease (CHD). In these trials, the
      incidence of death from CHD or the combined endpoint of death from CHD or
      nonfatal myocardial infarction was significantly lower in pravastatin than in
      placebo recipients. Pravastatin is well tolerated in the elderly, and adverse
      effects considered related to therapy are minimal. The most commonly occurring
      adverse events included gastrointestinal events, renal or genital system events,
      respiratory disorders, headaches and musculoskeletal pain. CONCLUSION:
      Pravastatin effectively lowers serum TC and LDL-C levels and, as demonstrated in
      major clinical outcome trials, reduces coronary events in elderly patients with
      hypercholesterolaemia or normal cholesterol levels. Pravastatin is well tolerated
      and as such should be considered a first-line agents for primary or secondary
      prevention in older individuals with evident CHD or multiple risk factors for
      CHD.

PMID- 14651450
TI  - Visual-visual nonidentity matching assessment: a worthwhile addition to the
      assessment of basic learning abilities test.
AB  - The Assessment of Basic Learning Abilities test (ABLA) is a useful tool for
      choosing appropriate training tasks for persons with developmental disabilities.
      This test assesses the ease or difficulty with which persons are able to learn
      six hierarchically positioned discrimination tasks. A visual-visual nonidentity
      matching prototype task was examined to assess its (a). relation to the ABLA
      hierarchy, (b). predictive validity, and (c). test-retest reliability. Results
      from 23 participants with developmental disabilities suggest that visual-visual
      nonidentity matching is a worthwhile addition to the ABLA test and is positioned
      in the ABLA hierarchy above Level 4 (visual-visual identity matching) and below
      Level 6 (auditory-visual discrimination). The prototype visual-visual nonidentity
      matching task also demonstrated high predictive validity and test-retest
      reliability.

PMID- 14651451
TI  - Substantial genetic influence on mild mental impairment in early childhood.
AB  - We report the first major genetic study of mild mental impairment. From a
      representative sample of 3886 twins (1314 monozygotic, 1296 dizygotic same-sex,
      and 1276 dizygotic opposite-sex), the lowest 5% were selected on a composite
      measure of verbal and nonverbal abilities assessed by parents when the twins were
      2, 3, and 4 years of age. Twin concordances for mild mental impairment were 74%
      for monozygotic twins, 45% for same-sex, and 36% for opposite-sex dizygotic
      twins, indicating substantial genetic influence. Model-fitting analyses estimated
      group heritability as.49, which is significantly greater than heritability for
      the rest of the population in early childhood. These results suggest that mild
      mental impairment is a good target for neuroscience research on global brain
      function and dysfunction.

PMID- 14651452
TI  - Relationships between psychiatric conditions and behavior problems among adults
      with mental retardation.
AB  - Adults with predominantly severe and profound mental retardation (N = 180) who
      lived in a developmental center were assessed with the Behavior Problems
      Inventory and the Diagnostic Assessment for the Severely Handicapped-II.
      Individuals with self-injurious, stereotyped, or aggressive/destructive behavior
      had generally higher psychopathology scores than individuals without, and the
      presence of behavior problems increased the likelihood of almost all psychiatric
      conditions up to three-fold. Factor analysis revealed that behavior problems
      tended to be associated with psychiatric conditions conventionally linked with
      behavior problems. A Self-Injury and Aggression/Destruction factor was related to
      impulse control and conduct problems, and a Stereotyped Behavior factor was
      linked to pervasive developmental disabilities and somewhat less so to
      schizophrenia. Stereotyped Behavior factor was independent of the Self
      Injury/Aggression/Destruction factor.

PMID- 14651453
TI  - Quantifying temporal distributions of self-injurious behavior: defining bouts
      versus discrete events.
AB  - An objective method is presented to group discrete self-injurious behavior (SIB)
      events into bouts. Survival analysis was used to determine how long after an SIB
      the probability of observing a subsequent SIB remained elevated. This estimated
      bout length criterion time point was determined individually for 19 subjects with
      developmental disorders and severe SIB. Bout length criterion estimates ranged
      from.6 to 15.5 seconds. When participants' SIBs were grouped into bouts using the
      bout length criterion estimate, the rate of bouts and the average number of SIBs
      in each bout were found to be more stable than the rate of individual SIBs. This
      approach may facilitate research on factors that initiate and maintain SIB.

PMID- 14651454
TI  - Benjamin Dann Walsh: pioneer entomologist and proponent of Darwinian theory.
AB  - Many entomologists are generally unacquainted with the life and scientific
      contributions of Benjamin Dann Walsh, the first State Entomologist of Illinois
      and an early proponent of Darwinian theory. This historical oversight is
      unfortunate because Walsh was both a pioneer in entomology and the only
      entomologist of his and Darwin's generation to support and contribute to Darwin's
      revolutionary theory of species origin. In this review, I attempt to return Walsh
      to his rightful place among the more fascinating and progressive scientists of
      the nineteenth century. The review comprises three sections: the first provides a
      biographical sketch of Walsh's rich and varied life in England and the United
      States; the second considers his entomological endeavors and legacy; and the
      third argues for Walsh's prescient advocacy of, and contributions to,
      evolutionary theory. Also included are passages from some of Walsh's publications
      and excerpts from his correspondence with Darwin and notable entomologists.

PMID- 14651455
TI  - Functional ecology of immature parasitoids.
AB  - Recently, there has been exciting progress in our understanding of the behavioral
      and evolutionary ecology of immature parasitoids. Developing parasitoids face a
      diversity of ecological constraints, and parasitism success involves decisions
      and responses made by immature parasitoids to find a host and solve conflicts
      with five potential antagonists: host, mother, siblings, competitors, and natural
      enemies. In this review we synthesize and interpret results from studies on (a)
      the convergent evolution of host selection behavior of first-instar larvae and
      females in hymenopteran, dipteran, and coleopteran families; (b) the competitive
      interactions between larval parasitoids and the evolution of gregariousness; (c)
      the susceptibility of parasitized hosts to predation; and (d) the ability of
      parasitoids to manipulate the behavior of the host. We discuss how ecological
      interactions between juvenile parasitoids and their hosts, competitors, and
      natural enemies influence the evolution of parasitoid life-history strategies,
      and why the integration of functional aspects of the ecology of immature
      parasitoids provides a reliable framework for effective host-parasitoid
      population models and formulation of biological control solutions.

PMID- 14651456
TI  - Insect walking and robotics.
AB  - With the advent of significant collaborations between researchers who study
      insect walking and robotics engineers interested in constructing adaptive legged
      robots, insect walking is once again poised to make a more significant scientific
      contribution than the numbers of participants in the field might suggest. This
      review outlines current knowledge of the physiological basis of insect walking
      with an emphasis on recent new developments in biomechanics and genetic
      dissection of behavior, and the impact this knowledge is having on robotics.
      Engineers have begun to team with neurobiologists to build walking robots whose
      physical design and functional control are based on insect biology. Such an
      approach may have benefits for engineering, by leading to the construction of
      better-performing robots, and for biology, by allowing real-time and real-world
      tests of critical hypotheses about how locomotor control is effected. It is
      argued that in order for the new field of biorobotics to have significant
      influence it must adopt criteria for performance and an experimental approach to
      the development of walking robots.

PMID- 14651457
TI  - The gut bacteria of insects: nonpathogenic interactions.
AB  - The diversity of the Insecta is reflected in the large and varied microbial
      communities inhabiting the gut. Studies, particularly with termites and
      cockroaches, have focused on the nutritional contributions of gut bacteria in
      insects living on suboptimal diets. The indigenous gut bacteria, however, also
      play a role in withstanding the colonization of the gut by non-indigenous species
      including pathogens. Gut bacterial consortia adapt by the transfer of plasmids
      and transconjugation between bacterial strains, and some insect species provide
      ideal conditions for bacterial conjugation, which suggests that the gut is a "hot
      spot" for gene transfer. Genomic analysis provides new avenues for the study of
      the gut microbial community and will reveal the molecular foundations of the
      relationships between the insect and its microbiome. In this review the
      intestinal bacteria is discussed in the context of developing our understanding
      of symbiotic relationships, of multitrophic interactions between insects and
      plant or animal host, and in developing new strategies for controlling insect
      pests.

PMID- 14651458
TI  - Regulation of intermediary metabolism and water balance of insects by
      neuropeptides.
AB  - Neuropeptides regulate all important physiological, developmental, and behavioral
      processes in insects. Here, I review two major physiological events that are
      hormonally controlled, namely intermediary metabolism and ion and water
      transport. Peptides belonging to the family of adipokinetic hormones (AKHs)
      increase hemolymph carbohydrates, lipids, and proline by activating the enzyme
      glycogen phosphorylase or lipase in the fat body. Moreover, these pleiotropic and
      multifunctional peptides inhibit protein-, lipid-, and RNA synthesis, and
      stimulate the frequency of contraction of certain muscles. Diuretic hormones that
      are related to the vertebrate corticotropin-releasing factor (CRF-related DHs) or
      belong to the family of kinins (which also have a myotropic action) or the
      cardioacceleratory peptides (CAPs), which increase the frequency of the
      heartbeat, all stimulate the secretion of fluid in Malpighian tubules (MTs) in
      vitro. Only a few true antidiuretic hormones are known: those from mealworms that
      inhibit the fluid transport in MTs in vitro, probably neuroparsins that stimulate
      water absorption by everted rectal sacs in vitro, and the desert locust's ion
      transport peptide (ITP). Biosynthesis, release, receptors, mode of action,
      inactivation, structure-activity studies, and biological functions are discussed
      for the various peptides.

PMID- 14651459
TI  - Long-term, large-scale biomonitoring of the unknown: assessing the effects of
      insecticides to control river blindness (onchocerciasis) in West Africa.
AB  - The control of river blindness (onchocerciasis), a human disease transmitted by
      black flies, has been an economic and public health success in West Africa. It
      involved insecticide applications to as many as 50,000 km of rivers, almost
      weekly, in 11 countries between 1974 and 2002. The long-term biomonitoring of the
      effects of insecticide use on the nontarget invertebrate (primarily insect) and
      fish communities was initially designed on the basis of limited knowledge
      available for West African rivers and on information from other areas. Routine
      monitoring surveys demonstrated little effect on fish but produced inconclusive
      results for invertebrates. Research conducted beyond these surveys and current
      views in river and general ecology indicate that permanent damage to
      invertebrates from insecticiding was unlikely. The scientific progress made
      during the 29 years of this biomonitoring program is relevant to future, large
      scale, long-term programs worldwide.

PMID- 14651460
TI  - Venezuelan equine encephalitis.
AB  - Venezuelan equine encephalitis virus (VEEV) remains a naturally emerging disease
      threat as well as a highly developed biological weapon. Recently, progress has
      been made in understanding the complex ecological and viral genetic mechanisms
      that coincide in time and space to generate outbreaks. Enzootic, equine
      avirulent, serotype ID VEEV strains appear to alter their serotype to IAB or IC,
      and their vertebrate and mosquito host range, to mediate repeated VEE emergence
      via mutations in the E2 envelope glycoprotein that represent convergent
      evolution. Adaptation to equines results in highly efficient amplification, which
      results in human disease. Although epizootic VEEV strains are opportunistic in
      their use of mosquito vectors, the most widespread outbreaks appear to involve
      specific adaptation to Ochlerotatus taeniorhynchus, the most common vector in
      many coastal areas. In contrast, enzootic VEEV strains are highly specialized and
      appear to utilize vectors exclusively in the Spissipes section of the Culex
      (Melanoconion) subgenus.

PMID- 14651461
TI  - Galling aphids: specialization, biological complexity, and variation.
AB  - Gall-inducing aphids are host specific in the gall stage. Most species alternate
      between trees (the primary host), where the gall is induced, and shrubs and
      grasses (secondary hosts). Parthenogenesis during most of their life cycle is
      interrupted by a single stage of sexual reproduction on the primary host. Apart
      from these general characteristics, galling aphids present some of the most
      complex and diverse life histories in the insect world. In this article I review
      the specialized characteristics of galling aphids, as well as their complex and
      diverse life histories, as reported in the past 20 years.

PMID- 14651462
TI  - Population genetics of autocidal control and strain replacement.
AB  - The concept that an insect species' genome could be altered in a manner that
      would result in the control of that species (i.e., autocidal control) or in the
      replacement of a pestiferous strain of the species with a more benign genotype
      was first proposed in the mid-twentieth century. A major research effort in
      population genetics and ecology followed and led to the development of a set of
      classical genetic control approaches that included use of sterile males,
      conditional lethal genes, translocations, compound chromosomes, and microbe
      mediated infertility. Although there have been a number of major successes in
      application of classical genetic control, research in this area has declined in
      the past 20 years for technical and societal reasons. Recent advances in
      molecular biology and transgenesis research have renewed interest in genetically
      based control methods because these advances may remove some major technical
      problems that have constrained effective genetic manipulation of pest species.
      Population genetic analyses suggest that transgenic manipulations may enable
      development of strains that would be 10 to over 100 times more efficient than
      strains developed by classical methods. Some of the proposed molecular approaches
      to genetic control involve modifications of classical approaches such as
      conditional lethality, whereas others are novel. Experience from the classical
      era of genetic control research indicates that the population structure and
      population dynamics of the target population will determine which, if any,
      genetic control approaches would be appropriate for addressing a specific
      problem. As such, there continues to be a need for ongoing communication between
      scientists who are developing strains and those who study the native pest
      populations.

PMID- 14651463
TI  - Biological control of cereal aphids in north america and mediating effects of
      host plant and habitat manipulations.
AB  - The predator and parasitoid fauna associated with cereal aphids is described,
      emphasizing the fauna associated with classical biological control efforts
      against the greenbug and Russian wheat aphid. We focus on literature from North
      America and include work from Europe and elsewhere when it is desirable to draw
      contrasts between approaches that affect cereal aphid biological control. Effects
      on natural enemies of cereal aphids are described that appear associated with
      plant traits that are innate, bred, or induced by aphid feeding. Examples of
      habitat manipulations, within and bordering cereal fields and within the broader
      landscape in which cereal production resides, affecting predators and parasitoids
      of cereal aphids are presented. These mediating effects of host plant and habitat
      manipulations on cereal aphid biological control provide significant and
      underexplored avenues to optimize cereal aphid management.

PMID- 14651464
TI  - The biology of xylem fluid-feeding insect vectors of Xylella fastidiosa and their
      relation to disease epidemiology.
AB  - Xylophagous leafhopppers are common and abundant insects of tropical and
      subtropical environments and play important ecological roles in these ecosystems.
      The feeding biology of these insects is unique in terms of their high feeding
      rates and a digestive physiology that allows them to assimilate amino acids,
      organic acids, and sugars at approximately 99% efficiency. For those species well
      studied, fluctuations in plant xylem chemistry and tension appear to determine
      the diurnal and seasonal use of their host plants. Relatively few species of
      xylem fluid-feeding leafhoppers are considered important pests in commercial
      agriculture, as they transmit the bacterial plant pathogen Xylella fastidiosa. X.
      fastidiosa induces diseases of grapevines, citrus, coffee, almond, alfalfa, stone
      fruits, landscape ornamentals, and native hardwoods for which there is no cure.
      Two Xylella diseases, citrus variegated chlorosis (CVC) and Pierce's disease (PD)
      of grapevines, have emerged as important issues within the past decade. In
      Brazil, CVC became important in the early 1990s and has now expanded throughout
      many citrus-growing areas of South America and threatens to spread to North
      America. The recent establishment of the exotic glassy-winged sharpshooter
      (Homalodisca coagulata) in California now threatens much of the United States'
      wine grape, table grape, and almond production. The spread of H. coagulata
      throughout southern California and the spread of CVC northward from Argentina
      through Brazil exemplifies the biological risks from exotic species. The
      occurrence and epidemiology of leafhopper-vectored Xylella diseases are
      discussed.

PMID- 14651465
TI  - Defensive behavior of honey bees: organization, genetics, and comparisons with
      other bees.
AB  - One key advantage of eusociality is shared defense of the nest, brood, and stored
      food; nest defense plays an important role in the biology of eusocial bees.
      Recent studies on honey bees, Apis mellifera, have focused on the placement of
      defensive activity in the overall scheme of division of labor, showing that guard
      bees play a unique and important role in colony defense. Alarm pheromones
      function in integrating defensive responses; honey bee alarm pheromone is an
      excellent example of a multicomponent pheromonal blend. The genetic regulation of
      defensive behavior is now better understood from the mapping of quantitative
      trait loci (QTLs) associated with variation in defensiveness. Colony defense in
      other eusocial bees is less well understood, but enough information is available
      to provide interesting comparisons between A. mellifera and other species of
      Apis, as well as with allodapine, halictine, bombine, and meliponine bees. These
      comparative studies illustrate the wide variety of evolutionary solutions to
      problems in colony defense in the Apoidea.

PMID- 14651466
TI  - Wasp parasitoid disruption of host development: implications for new biologically
      based strategies for insect control.
AB  - Wasp parasitoids use a variety of methods to commandeer their insect hosts in
      order to create an environment that will support and promote their own
      development, usually to the detriment of the host insect. Parasitized insects
      typically undergo developmental arrest and die sometime after the parasitoid has
      become independent of its host. Parasitoids can deactivate their host's immune
      system and effect changes in host hormone titers and behavior. Often, host
      tissues or organs become refractory to stimulation by tropic hormones. Here we
      present an overview of the manipulative capabilities of wasp-injected calyx fluid
      containing polydnaviruses and venom, as well as the parasitoid larva and the
      teratocytes that originate from the serosal membrane that surrounds the
      developing embryo of the parasitoid. Possibilities for using regulatory molecules
      produced by the parasitoid or its products that would be potentially useful in
      developing new, environmentally safe insect control agents are discussed.

PMID- 14651467
TI  - Eradication of the melon fly, Bactrocera cucurbitae, in Japan: importance of
      behavior, ecology, genetics, and evolution.
AB  - The melon fly, Bactrocera cucurbitae, is a destructive insect of cucurbit and
      other fruits. It invaded the Southwestern Islands of Japan from 1919 to 1974. The
      sterile insect technique (SIT) was successfully applied from 1972 to 1993 to
      eradicate the melon fly. Technical research into SIT functions, such as
      suppression of density, mass-rearing, sterilization, shipment, release,
      evaluation of efficacy, and quality control of mass-reared insects, was conducted
      for this eradication project. Fundamental research into the dispersion, mating
      and oviposition behavior, population dynamics and estimation of density,
      eradication models, spatial distribution, genetics, and evolution of the melon
      fly was also undertaken and supported the success of the eradication project.

PMID- 14651468
TI  - The African honey bee: factors contributing to a successful biological invasion.
AB  - The African honey bee subspecies Apis mellifera scutellata has colonized much of
      the Americas in less than 50 years and has largely replaced European bees
      throughout its range in the New World. The African bee therefore provides an
      excellent opportunity to examine the factors that influence invasion success. We
      provide a synthesis of recent research on the African bee, concentrating on its
      ability to displace European honey bees. Specifically, we consider (a) the
      genetic composition of the expanding population and the symmetry of gene flow
      between African and European bees, (b) the mechanisms that favor the preservation
      of the African genome, and (c) the possible range and impact of the African bee
      in the United States.

PMID- 14651469
TI  - Phylogeny and biology of neotropical orchid bees (Euglossini).
AB  - Orchid bees (Euglossini), noted for their brilliant iridescence, are elusive
      pollinators throughout the American tropics. Males are especially important in
      the pollination of some orchids, from which they collect aromatic fragrances
      thought to play a role in territorial display and courtship. The tribe contains
      approximately 190 described species divided among five genera, distributed from
      Mexico to central Argentina. Relatively intense study of their biology in the
      1960s through the mid-1980s shed light on their nesting biology, chemical
      ecology, and classification. Vigorous taxonomic research led to the naming of
      many new species, revisions, and checklists, but phylogenetic studies were
      scarce. In the two decades following the last comprehensive review, phylogenetic
      research has resulted in new hypotheses of generic relationships, and further
      examination of male display has led to additional interpretations. Females in
      natural and artificial nesting cavities have revealed social interactions and
      additional details of parasitism within the nest. This review emphasizes areas in
      need of more study, particularly phylogeny, phylogeography, chemosensory ecology,
      and comparative behavior, and highlights how historical context can guide future
      research.

PMID- 14651470
TI  - Plant-insect interactions in fragmented landscapes.
AB  - Population and community ecology need a large-scale perspective because local
      patterns (of biodiversity) and processes (trophic interactions) are influenced by
      the regional setting. The ratio of the foraging range and/or dispersal ability to
      the distance between landscape elements influences local population dynamics. The
      spatial scale experienced by a species may be linked to its trophic level and
      also to traits such as body size, resource specialization, rarity, and population
      size variability. Hence, communities are assemblages of species with different
      spatial strategies. Effects of habitat loss and habitat fragmentation on plant
      herbivore, herbivore-enemy, as well as plant-pollinator interactions are
      contingent on species and landscape. Metapopulation theory provides a unifying
      frame to approach plant-insect systems across fragmented landscape, although the
      landscape context is often ignored. In some cases theory is far ahead of
      empirical research. We call for more population data on large spatial and
      temporal scales to better understand plant-insect populations across fragmented
      landscapes.

PMID- 14651471
TI  - Polydnavirus genes and genomes: emerging gene families and new insights into
      polydnavirus replication.
AB  - Polydnavirus genome sequencing is providing new insights into viral genome
      organization and viral gene function. Sequence analyses demonstrate that the
      genomes of these viral mutualists are largely noncoding but maintain genes and
      gene families that are unrelated to other viral genes. Interestingly, these
      organizational patterns in polydnavirus genomes are evident in both the
      bracovirus and ichnovirus genera, even though these two genera are evolutionarily
      unrelated. The identity and function of some polydnavirus gene families are
      considered with some functions experimentally supported and others implied by
      homology relationships with known insect genes. The evidence relative to
      polydnavirus origins and evolution is considered but remains an area of
      speculation. However, sequencing of these viral genomes has been informative and
      provides opportunities for productive investigation of these unusual mutualistic
      insect viruses.

PMID- 14651472
TI  - Human lice and their control.
AB  - Current research on human louse biology has focused on the long-standing debate
      about speciation of head and body lice but using new tools of DNA and enzyme
      analysis. These studies have indicated that head and body lice from the same
      geographical zone may be more closely allied than insects inhabiting the same
      ecological niche in other regions. However, the majority of research over the
      past decade has involved clinical aspects including transmission, treatment, and
      the appearance and identification of resistant strains within populations of
      lice. Despite advances, there is a need for a better understanding of louse
      biology, as existing therapies fail and lice remain potential vectors of disease
      for millions of people.

PMID- 14651473
TI  - Plasma urocortin in human systolic heart failure.
AB  - Urocortin (UCN), a member of the corticotrophin-releasing factor family, is
      expressed in heart, brain and gut. UCN has potent cardiostimulatory,
      cardioprotective, vasodilator and diuretic/natriuretic effects, and cardiac UCN
      expression is increased in heart failure (HF). In the present study, we
      investigated plasma levels of UCN in 119 patients with HF and 212 age- and gender
      matched controls to clarify its relationship with gender and disease severity.
      UCN was elevated in HF [normal males, 19.5 (3.9-68.8) pmol/l and HF males, 50.2
      (6.9-108.2) pmol/l, P < 0.0005; normal females, 14.2 (3.9-53.5) pmol/l and HF
      females, 21.8 (3.9-112.5) pmol/l, P < 0.001; values are medians (range)]. The
      relative increase was greater in males than females ( P < 0.03). UCN fell with
      increasing age, especially in HF patients ( r(s) = -0.56, P < 0.0005) and with
      increasing New York Heart Association (NYHA) class ( r(s) = -0.55, P < 0.0005).
      The fall in UCN levels with increasing NYHA class was reinforced by a significant
      correlation between UCN and ejection fraction ( r(s) = 0.45, P < 0.0005) in HF
      patients. Although receiver operating characteristic (ROC) curves for diagnosis
      of all HF cases yielded an area under the curve (AUC) of 0.76, ROC AUCs for
      patients with early HF (NYHA class I and II) were better (0.91). ROC AUCs for
      logistic models incorporating N-terminal probrain natriuretic peptide (N-BNP) and
      UCN were better than either peptide alone. In conclusion, plasma UCN is elevated
      in HF, especially in its early stages. Its decline with increasing HF severity
      may expedite disease progression due to diminished cardioprotective/anti
      inflammatory effects. UCN measurement may also complement N-BNP in the diagnosis
      of early HF.

PMID- 14651474
TI  - Redox regulation of DNA binding activity of DREF (DNA replication-related element
      binding factor) in Drosophila.
AB  - DREF [DRE (DNA replication-related element) binding factor] is an 80 kDa
      polypeptide homodimer which plays an important role in regulating cell
      proliferation-related genes. Both DNA binding and dimer formation activities are
      associated with residues 16-115 of the N-terminal region. However, the mechanisms
      by which DREF dimerization and DNA binding are regulated remain unknown. Here, we
      report that the DNA binding activity of DREF is regulated by a redox mechanism,
      and that the cysteine residues are involved in this regulation. Electrophoretic
      mobility shift analysis using Drosophila Kc cell extracts or recombinant DREF
      proteins indicated that the DNA binding domain is sufficient for redox
      regulation. Site-directed mutagenesis and transient transfection assays showed
      that Cys59 and/or Cys62 are critical both for DNA binding and for redox
      regulation, whereas Cys91 is dispensable. In addition, experiments using Kc cells
      indicated that the DNA binding activity and function of DREF are affected by the
      intracellular redox state. These findings give insight into the exact nature of
      DREF function in the regulation of target genes by the intracellular redox state.

PMID- 14651475
TI  - A novel omega3-fatty acid desaturase involved in the biosynthesis of
      eicosapentaenoic acid.
AB  - Long-chain n-3 PUFAs (polyunsaturated fatty acids) such as EPA (eicosapentaenoic
      acid; 20:5 n-3) have important therapeutic and nutritional benefits in humans. In
      plants, cyanobacteria and nematodes, omega3-desaturases catalyse the formation of
      these n-3 fatty acids from n-6 fatty acid precursors. Here we describe the
      isolation and characterization of a gene ( sdd17 ) derived from an EPA-rich
      fungus, Saprolegnia diclina, that encodes a novel omega3-desaturase. This gene
      was isolated by PCR amplification of an S. diclina cDNA library using
      oligonucleotide primers corresponding to conserved regions of known omega3
      desaturases. Expression of this gene in Saccharomyces cerevisiae, in the presence
      of various fatty acid substrates, revealed that the recombinant protein could
      exclusively desaturate 20-carbon n-6 fatty acid substrates with a distinct
      preference for ARA (arachidonic acid; 20:4 n-6), converting it into EPA. This
      activity differs from that of the known omega3-desaturases from any organism.
      Plant and cyanobacterial omega3-desaturases exclusively desaturate 18-carbon n-6
      PUFAs, and a Caenorhabditis elegans omega3-desaturase preferentially desaturated
      18-carbon PUFAs over 20-carbon substrates, and could not convert ARA into EPA
      when expressed in yeast. The sdd17 -encoded desaturase was also functional in
      transgenic somatic soya bean embryos, resulting in the production of EPA from
      exogenously supplied ARA, thus demonstrating its potential for use in the
      production of EPA in transgenic oilseed crops.

PMID- 14651476
TI  - Substitutions in hamster CAD carbamoyl-phosphate synthetase alter allosteric
      response to 5-phosphoribosyl-alpha-pyrophosphate (PRPP) and UTP.
AB  - CPSase (carbamoyl-phosphate synthetase II), a component of CAD protein
      (multienzymic protein with CPSase, aspartate transcarbamylase and dihydro-orotase
      activities), catalyses the regulated steps in the de novo synthesis of
      pyrimidines. Unlike the orthologous Escherichia coli enzyme that is regulated by
      UMP, inosine monophosphate and ornithine, the mammalian CPSase is allosterically
      inhibited by UTP, and activated by PRPP (5-phosphoribosyl-a-pyrophosphate) and
      phosphorylation. Four residues (Thr974, Lys993, Lys954 and Thr977) are critical
      to the E. coli inosine monophosphate/UMP-binding pocket. In the present study,
      three of the corresponding residues in the hamster CPSase were altered to
      determine if they affect either PRPP activation or UTP inhibition. Substitution
      of the hamster residue, positionally equivalent to Thr974 in the E. coli enzyme,
      with alanine residue led to an enzyme with 5-fold lower activity and a near loss
      of PRPP activation. Whereas replacement of the tryptophan residue at position 993
      had no effect, an Asp992-->Asn substitution yielded a much-activated enzyme that
      behaved as if PRPP was present. The substitution Lys954-->Glu had no effect on
      PRPP stimulation. Only modest decreases in UTP inhibitions were observed with
      each of the altered CPSases. The results also show that while PRPP and UTP can
      act simultaneously, PRPP activation is dominant. Apparently, UTP and PRPP have
      distinctly different associations within the mammalian enzyme. The findings of
      the present study may prove relevant to the neuropathology of Lesch-Nyhan
      syndrome

PMID- 14651478
TI  - Detection and localization of two constitutive NOS isoforms in bull spermatozoa.
AB  - Bull spermatozoa were examined for the presence and localization of constitutive
      Nitric Oxide Synthase (NOS), as nitric oxide (NO) is involved in calcium
      dependent capacitation. In bull spermatozoa, NO generation is enhanced by l
      arginine (3 microm) and abolished by the NOS-inhibitor N-nitro-l-arginine methyl
      ester (l-NAME). In addition, presence of NOS in bull spermatozoa was verified by
      immunohistochemistry, revealing the existence of both neuronal NOS (nNOS) and
      endothelial NOS (eNOS) immunoreaction. These findings were confirmed by Western
      blot technique, showing immunoreactive bands at 161 kDa (nNOS) and 133 kDa
      (eNOS). Confocal laser microscopy localized nNOS related immunofluorescence at
      the acrosome cap of sperms and their flagellum-mainpart. This technique also
      identified eNOS staining spread over the spermatozoan head. In conclusion,
      immunohistochemistry, Western blot technique, and NO generation suggest the
      presence of n- and eNOS in bull spermatozoa.

PMID- 14651479
TI  - Development of the areola in the early placenta of the one-humped camel (Camelus
      dromedarius): a light, scanning and transmission electron microscopical study.
AB  - This study aimed to elucidate development of the areola in the early dromedary
      placenta in comparison with that of the pig and mare. Placental tissues from 25
      pregnant camels were obtained from Cairo abattoir and prepared for light,
      scanning and transmission electron microscopy by routine methods. Vascular casts
      were made by injection of 4 : 1 liquid plastic mixture of mercox and
      methylmethacrylate. Areolar formation was first observed at 4.5 cm curved-crown
      rump CVR length, while by 5-9 cm CVR length, the endometrial surface was uneven
      and studded with numerous uterine gland openings, where corresponding foetal
      areolae were barely detectable and the foetal areolar cells were of variable
      appearance and covered with long microvilli. At 10-13 cm CVR length the uterine
      gland openings developed irregular folds and the maternal areolar cells showed
      numerous apical blebs. At 14-29 cm CVR length the foetal areolae showed a great
      increase in height at the expense of their width. At 30-34 cm (CVR) length the
      maternal areolae appeared discoid and sharply demarcated from the surrounding
      inter-areolar tissues and the foetal areolae were rounded to irregular in shape
      with well-developed areolar rims. The vascular casts showed a widely meshed
      capillary network on the maternal areola, connecting with the pre- and post
      capillary vessels, whereas the foetal side showed a relatively dense capillary
      meshwork. These studies indicate that the areola in the placenta of the one
      humped camel is of the regular type like in the pig, and is poorly vascularized.

PMID- 14651480
TI  - Afferent and efferent connections of the nucleus rotundus demonstrated by WGA-HRP
      in the chick.
AB  - Organization of the fibre connections in the chick nucleus rotundus (Rt) was
      investigated by an axonal tracing method using wheat germ agglutinin conjugated
      to horseradish peroxidase (WGA-HRP). After an injection of WGA-HRP into the Rt,
      labelled neurones were observed in the striatum griseum centrale (SGC) in both
      sides of the tectum (TO) and in the ipsilateral nucleus subpretectalis/nucleus
      interstito-pretecto-subpretectalis (SP/IPS). Labelled fibres and terminals were
      also found in the ipsilateral ectostriatum (Ect). These fibre connections were
      topographically organized rostrocaudally. In the TO-Rt projection, the rostral
      and the dorsocaudal parts of the Rt received afferents from the superficial part
      of the SGC, the middle part of the Rt received afferents from the intermediate
      part of the SGC, and the ventrocaudal part of the Rt received mainly fibres from
      the deep part of the SGC. These topographic projections were accompanied by a
      considerable number of diffuse projections to the thalamic regions surrounding
      the Rt. In addition, the rostral and middle caudal parts of the Rt received
      afferents from the lateral and medial parts of the SP/IPS, respectively, and
      respective parts of the Rt sent efferents to the lateral and medial parts of the
      Ect.

PMID- 14651477
TI  - Regulation of glycogen metabolism in cultured human muscles by the glycogen
      phosphorylase inhibitor CP-91149.
AB  - Pharmacological inhibition of liver GP (glycogen phosphorylase), which is
      currently being studied as a treatment for Type II (non-insulin-dependent)
      diabetes, may affect muscle glycogen metabolism. In the present study, we
      analysed the effects of the GP inhibitor CP-91149 on non-engineered or GP
      overexpressing cultured human muscle cells. We found that CP-91149 treatment
      decreased muscle GP activity by (1) converting the phosphorylated AMP-independent
      a form into the dephosphorylated AMP-dependent b form and (2) inhibiting GP a
      activity and AMP-mediated GP b activation. Dephosphorylation of GP was exerted,
      irrespective of incubation of the cells with glucose, whereas inhibition of its
      activity was synergic with glucose. As expected, CP-91149 impaired the
      glycogenolysis induced by glucose deprivation. CP-91149 also promoted the
      dephosphorylation and activation of GS (glycogen synthase) in non-engineered or
      GP-overexpressing cultured human muscle cells, but exclusively in glucose
      deprived cells. However, this inhibitor did not activate GS in glucose-deprived
      but glycogen-replete cells overexpressing PTG (protein targeting to glycogen),
      thus suggesting that glycogen inhibits the CP-91149-mediated activation of GS.
      Consistently, CP-91149 promoted glycogen resynthesis, but not its
      overaccumulation. Hence, treatment with CP-91149 impairs muscle glycogen
      breakdown, but enhances its recovery, which may be useful for the treatment of
      Type II (insulin-dependent) diabetes.

PMID- 14651481
TI  - Morphological and histochemical characterization of the mucosa of the digestive
      tract in Engraulis anchoita.
AB  - The histomorphological aspects as well as the histochemical content and
      distribution of glycoproteins (GPs) in the mucosa of the digestive tract of the
      anchovy Engraulis anchoita were studied. The buccopharyngeal cavity is lined by a
      squamous stratified epithelium with mucous superficial cells; the oesophagus
      shows two zones, cranial with a squamous stratified epithelium with mucous
      superficial cells and caudal with a columnar secretory epithelium. Finally, the
      stomach presents both the cranial and pyloric portion lined with a simple
      columnar epithelium. Tubular branched glands, formed by a single type of
      glandular cell, located along the stomach, are more numerous in the cranial
      portion. The GPs were identified with (1) oxidizable vicinal diols; (2) sialic
      acids and some of their chain variants, C7 or C9; (3) sialic acid residues with O
      acyl substitution at C7 or C8; (4) carboxyl groups and (5) sulphate groups.
      Histochemical tests showed that the buccopharyngeal cavity presented the largest
      amount of the different types of mucosubstances. Epithelial secretory cells were
      found in the oesophagus, which synthesized a large quantity of
      sialosulphoglycoproteins likely to be related to a protective role. The surface
      epithelium of the stomach synthesizes and secretes acid and neutral GPs, probably
      related to the movement of fluids and to the absorption of easily digested
      substrates, respectively. Although great differences exist between different
      species, in E. anchoita as in other fish species, the wall of the digestive tract
      is composed of the four layers classically described for vertebrates. The GPs
      secreted by the epithelial cells are suggested to be important for the protection
      and inhibition of microorganisms. In addition, they are involved in enzymatic
      digestion of food, absorptive functions and lubrication of the alimentary tract.

PMID- 14651482
TI  - Morphology and comparative anatomy of circulus arteriosus cerebri in mammals.
AB  - The normal configuration of the arterial pattern at the base of the brain in
      rhesus monkeys, dogs, sheep, goats and rabbits is described. The length and
      diameter of all vessels of the circulus arteriosus cerebri are measured.
      Variations are compared in relation to that of the typical pattern present in
      humans. In rhesus monkeys, dogs and rabbits, the circle of Willis is almost
      similar to that in human beings except that in these animals, (i) the anterior
      cerebral arteries join each other to form a single median vessel; (ii) in dogs,
      rabbits, goats and sheep the anterior cerebellar artery is a branch of posterior
      cerebral artery, and (iii) in goats and sheep, a considerable length of the
      internal carotid artery contributes to the formation of circulus arteriosus while
      the posterior cerebral artery arises from the posterior communicating artery.

PMID- 14651483
TI  - The zonal distributions of alkaline phosphatase, adenosine triphosphatase,
      laminin, fibronectin and chondroitin 4-sulphate in growing rat humerus proximal
      epiphyseal cartilage: a histochemical and an immunohistochemical study.
AB  - Although there are many studies about epiphyseal cartilage extracellular matrix
      (ECM) macromolecules in bone formation, studies of their distribution and role in
      the mineralization of these components in growing rat humerus proximal epiphyseal
      cartilage have not been sufficiently detailed. The aim of this study was to
      determine the distributions of alkaline phosphatase (ALP), adenosine
      triphosphatase (ATPase), laminin, fibronectin and chondroitin 4-sulphate in
      growing rat humerus proximal epiphyseal cartilage. The rats were killed by
      cervical dislocation, and the humeri were removed, sectioned (6 and 10 microm) on
      a cryotome or paraffin microtome, and stained using histochemical and
      immunohistochemical methods. ALP and ATPase were markedly observed in the
      hypertrophy and calcifying cartilage. In addition, ATPase was found to be very
      strongly positive in the tangential zone of articular cartilage. Results of
      immunohistochemical staining for laminin, fibronectin and chondroitin 4-sulphate
      showed that the immunostaining was the heaviest in the tangential zone of
      articular cartilage. In growing epiphyseal plates, there were differences in the
      density of these macromolecules of chondrocytes as a function of the maturation
      process. In conclusion, these ECM macromolecules of epiphyseal cartilage may
      regulate the cell-cell and cell-matrix interactions as well as the matrix
      calcification during the ossification of epiphyseal cartilage.

PMID- 14651484
TI  - Subgross investigation of vessels originating from arcus aortae in guinea-pig
      (Cavia porcellus).
AB  - The vessels that originate from the aortic arch were studied in 16 adult guinea
      pigs. Two major vessels, the left subclavian artery and the brachiocephalic
      trunk, were easily identified as they were branching off from the aortic arch.
      The brachiocephalic trunk, at first branched off to the left common carotid
      artery and continued as a common trunk, which was then divided into the right
      subclavian artery and the right common carotid artery. The left subclavian artery
      branched off to the following vessels: the costacervical trunk, the internal
      thoracic artery, a common trunk from which the dorsal scapular artery and the
      vertebral artery originated, and the superficial cervical artery. The right
      subclavian artery branched off to the bronchoesophageal artery (in five
      cadavers), the caudal thyroid artery (in three cadavers) and the tracheal artery
      (in three cadavers) in addition to the above vessels. There were two vertebral
      arteries branching off to the right subclavian artery in all dissected cadavers.
      However, only 10 cadavers had two vertebral arteries originating from the left
      subclavian artery. The first vertebral artery originated from the common trunk,
      whereas the second vertebral artery arose from the dorsal scapular artery. The
      second vertebral artery entered the foramen transversarium of the seventh
      cervical vertebrae and anastomosed with the first vertebral artery just before
      entering the foramen transversarium of the sixth cervical vertebrae.

PMID- 14651485
TI  - The macroanatomical investigations on the aortic arch in porcupines (Hystrix
      cristata).
AB  - The anatomy of aortic arch in porcupine was studied. Angiography was applied to
      each of the three adult porcupines (two males, one female) following the
      injection of latex from the abdominal aorta for the examination of aortic arch.
      The results indicated that three arteries arose from aortic arch in porcupine.
      These were truncus brachiocephalicus, arteria carotis communis sinistra and
      arteria subclavia sinistra. The truncus brachiocephalicus in porcupine yielded
      arteria subclavia dextra and arteria carotis communis dextra. Truncus bicaroticus
      was absent. The origin of truncus costocervicalis (right) and arteria vertebralis
      (right) arose from a common root. Left or right axillary arteries seemed to be a
      continuation of subclavian arteries. The results of this study may contribute to
      the data in this area of science.

PMID- 14651486
TI  - Peculiar bundles of filaments in Leydig cells of the lesser mouse deer (Tragulus
      javanicus): an ultrastructural study.
AB  - Leydig cells of lesser mouse deer (Tragulus javanicus) testes were observed using
      light and transmission electron microscopies. Sexually mature lesser mouse deer
      were obtained in East Malaysia. The testes were perfused with 5% glutaraldehyde,
      postfixed with 1% OsO4, dehydrated in ethanol and embedded in Araldite. The
      semithin sections were cut, stained with toluidine blue and observed under light
      microscopy. The ultrathin sections were cut, stained with uranyl acetate and lead
      citrate, and examined using a JEM-1200 transmission electron microscope. As a
      result, two types of filament bundles were frequently recognized in Leydig cells,
      but not in other testicular cells. These bundles were clearly seen at even a
      light microscopic level. One type was bundles of actin filaments (approximately 5
      nm in diameter). These structures were found not only in the cytoplasm but also
      in the nucleus. The other type was bundles of intermediate filaments
      (approximately 10 nm in diameter). These structures were found only in the
      cytoplasm. The existence of filament bundles has never been reported in the
      testicular cells of another mammalian species. Thus, while bundles of actin and
      intermediate filaments are specifically present in the Leydig cells of the lesser
      mouse deer, their functions are still unclear.

PMID- 14651487
TI  - Morphology of canine cumulus-oocyte complexes in pre-pubertal bitches.
AB  - The morphology of canine cumulus-oocyte complexes (COCs) before puberty is still
      unknown. Therefore, the aim of our study was to elucidate the morphological
      characteristics of pre-pubertal oocytes and cumulus cells by light microscopy,
      scanning electron microscopy and transmission electron microscopy. The pre
      pubertal oocyte was characterized by accumulation of lipid yolk droplets in the
      cytoplasm as well as high energy metabolism, low protein synthesis and high
      transcriptional activity of the cumulus cells. The cumulus cells, which revealed
      a prominent nucleus and few cytoplasm, communicated with each other by few short
      processes and exhibited merely a small amount of processes reaching the oocyte.
      Our studies imply that both the oocyte and the cumulus cells of canine COCs
      before puberty reveal characteristic morphological features which are correlated
      with changes in oocyte metabolism and cumulus cell communication.

PMID- 14651488
TI  - Pax-7 immunoreactivity in the post-natal chicken central nervous system.
AB  - In this immunocytochemical study on the constitutive expression of Pax-7 protein
      in the postnatal chicken brain, Pax-7 showed region and cell type specific
      expression. In the optic tectum, only cells in grey matter showed positive
      immunoreactivities (IRs), whereas those in the white matters did not show any
      IRs. In thalamic nuclei and several pontine nuclei, we also localized Pax-7
      positive IRs. On the contrary, in the cerebellum, Pax-7 was mainly localized
      within the Bergmann glia, whereas Purkinje cells did not show any IRs. In double
      immunolabelling studies, most of the Pax-7 IRs did not originate from neuroglial
      cells such as oligodendrocytes, microglia or astrocytes, but from neurons, with
      the exception of Bergmann glia in the cerebellum. The presence of Pax-7 IRs in
      the adult chicken brain could suggest that Pax-7 might play a role in maintaining
      normal physiological function in some postnatal chicken brain cells.

PMID- 14651490
TI  - Safety in drug and alcohol research.

PMID- 14651494
TI  - The relative contribution of outcome domains in the total economic benefit of
      addiction interventions: a review of first findings.
AB  - AIMS: This paper provides a focused summary of the relative contribution of
      addiction intervention outcomes to total economic benefit, based upon a
      compilation of published economic studies from the United States. DESIGN: The
      relevant literature was searched extensively, and 11 economic studies were
      selected for review. SETTING: The selected addiction interventions address both
      alcohol use/abuse and illicit drug use/abuse and represent various treatment
      modalities, including a brief physician intervention and long-term residential
      programs. PARTICIPANTS: Study participants included community-based drug users,
      pregnant and/or parenting women, problem drinkers, and criminal offenders.
      MEASUREMENTS: These studies estimated the economic benefits of an addiction
      intervention(s) in terms of one or more of the following outcome domains:
      criminal activity, health services utilization, employment earnings, and
      expenditures on illicit drugs and alcohol. FINDINGS: The primary finding of this
      review was that avoided criminal activity was the greatest economic benefit of
      addiction interventions and contributed more, as a separate outcome domain, to
      the total economic benefit of addiction interventions than any other outcome
      domain. Reduced utilization of health care services was also a noteworthy
      economic benefit of addiction interventions. CONCLUSIONS: This study provides a
      detailed exposition of economic benefits estimation and highlights the potential
      impact of individual outcomes, thus providing a useful resource for substance
      abuse researchers and administrators as they design and evaluate future
      interventions.

PMID- 14651495
TI  - A hierarchy of gambling disorders in the community.
AB  - AIMS: To help refine the definition and diagnosis of gambling disorders, we
      investigated the distribution among US gamblers of the 10 DSM-IV criteria for
      Pathological Gambling. DESIGN: We drew data from two stratified random surveys (n
      = 2417, n= 530) of gambling behavior and consequences among community-based
      samples of US adults. A fully structured questionnaire, administered by trained
      lay interviewers, screened for the life-time prevalence of problem and
      Pathological Gambling. Per DSM-IV definitions, anyone meeting five or more of 10
      itemized criteria was considered a pathological gambler. We analyzed these
      criteria among all gamblers who met one or more criteria (n = 399). FINDINGS:
      Most gamblers who met only one or two criteria reported 'chasing their losses'.
      At subclinical levels (three to four criteria), gamblers also reported elevated
      rates of gambling-related fantasy: lying, gambling to escape and preoccupation.
      Pathological gamblers with five to seven criteria reported marked elevations of
      loss of control, withdrawal symptoms and tolerance (internalizing dimensions of
      dependence); risking their social relationships and needing to be bailed out
      financially (externalizing dimensions). Most of the highest-level pathological
      gamblers (eight to 10 criteria) reported committing illegal acts to support
      gambling. CONCLUSION: Dependence in a biobehavioral sense appears to be a
      hallmark of Pathological Gambling, but it marks only one threshold in a
      qualitative hierarchy of disorders beginning with a common subclinical behavior,
      'chasing'. Epidemiological assessments and future DSM revisions might consider
      explicit recognition of a problem gambling disorder, identifying people
      presenting some cognitive symptoms of Pathological Gambling but not clear signs
      of dependence. Pathological gamblers in turn appear to have two distinct levels
      of severity.

PMID- 14651496
TI  - Moving beyond a dichotomous classification for gambling disorders.

PMID- 14651497
TI  - Distribution of the DSM-IV criteria for pathological gambling.

PMID- 14651498
TI  - The fascination of psychometrics: commentary on Gerstein et al. (2003).

PMID- 14651500
TI  - Cannabis and educational achievement.
AB  - AIMS: To examine the relationship between cannabis use in adolescence/young
      adulthood and levels of educational attainment. DESIGN: Data were gathered over
      the course of a 25-year longitudinal study of a birth cohort of 1265 New Zealand
      children. MEASUREMENTS: Measures analysed included (a) frequency of cannabis use
      in adolescence and young adulthood (15-25 years); (b) levels of educational
      achievement to age 25 years; and (c) social, family and individual
      characteristics assessed prior to age 16. FINDINGS: Increasing cannabis use was
      associated with increasing risks of leaving school without qualifications,
      failure to enter university and failure to obtain a university degree. The
      association between cannabis use and leaving school without qualifications
      persisted after control for confounding factors. When due allowance was made for
      pre-existing levels of cannabis use there was no evidence to suggest the presence
      of reverse causal pathways in which lower educational achievement led to
      increased cannabis use. CONCLUSIONS: Findings support the view that cannabis use
      may act to decrease educational achievement in young people. It is likely that
      this reflects the effects of the social context within which cannabis is used
      rather than any direct effect of cannabis on cognitive ability or motivation.

PMID- 14651501
TI  - A contextual profile of club drug use among adults in Chicago.
AB  - AIMS: To better understand the prevalence, correlates, risk factors and context
      of club drug use among US adults in the City of Chicago. DESIGN: An Audio
      Computer-Assisted Self Interview was administered to a household probability
      sample of adults, aged 18-40 years, from June 2001 to January 2002. SETTING:
      Subjects were drawn from randomly selected households using a multi-stage area
      probability design. PARTICIPANTS: The data represent 627 randomly selected adult
      participants. MEASUREMENT: Weighted prevalence estimates with design-effect
      adjusted confidence intervals of life-time, past 12 month and past 30 day use of
      any club drug and of specific club drugs; prevalence of rave attendance, other
      drug use, motivation for use among club drug users; chi2 tests of significance,
      logistic regression and adjusted odds ratios. FINDINGS: Overall club drug
      prevalence rates were nearly twice those obtained for MDMA alone. Club drug users
      were more likely to use multiple illicit substances and to report having been in
      treatment for substance use. A majority of life-time club drug users never
      attended a rave although rave attendees were more likely to report frequent use
      of MDMA. Use was associated with gender, race and sexual orientation.
      CONCLUSIONS: Prevention research should be informed by further population-based
      research on club drug use. Research should not focus exclusively on rave
      attendees, as they are only a subset of club drug users. Research is needed on
      neurological and behavioral sequelae across different types of club drugs, gender
      differences in the impact of sexual orientation on club drug risk and on the
      effects of personality characteristics such as sensation seeking on club drug use
      behavior.

PMID- 14651502
TI  - Neighborhood effects on drug reporting.
AB  - AIMS: To examine whether neighborhood racial characteristics are associated with
      the under reporting of life time cocaine/crack use. DESIGN: A household survey of
      high-risk communities with above-average admissions to state-supported drug and
      alcohol treatment programs. SETTING: Chicago, Illinois, USA. PARTICIPANTS: A
      total of 303 adults. MEASURES: Self-reported use of cocaine/crack during a
      respondent's life time, hair test assays for cocaine use and level of
      neighborhood diversity measured using the Simpson Index. FINDINGS: Respondents
      from more segregated neighborhoods were more likely than those from diverse
      neighborhoods to under report life time cocaine/crack use. CONCLUSIONS:
      Neighborhood racial characteristics should be considered as an important factor
      in household surveys on illicit substance use.

PMID- 14651503
TI  - The role of an international nightlife resort in the proliferation of
      recreational drugs.
AB  - AIMS: The study compares types, frequencies and quantities of substances used by
      young people while holidaying in the international dance resort of Ibiza (Spain)
      with their patterns of use in the United Kingdom. It measures changes in
      substance use at both locations between 1999 and 2002 and examines the role of
      dance resorts in recruiting individuals into using new substances. DESIGN: Data
      were collected from visitors to Ibiza in 1999 (n = 846) and 2002 (n = 868).
      Information on drug use was surveyed through a short anonymous questionnaire.
      SETTING: Individuals were sampled at Ibiza airport just prior to returning to the
      UK. FINDINGS: Most individuals visiting Ibiza used illicit drugs in the United
      Kingdom (57.4% in 2002), with nearly all users continuing to use in Ibiza. Use of
      most drugs in Ibiza was characterized by binge behaviour, with many individuals
      using drugs 5 or more nights per week. Proportions using cocaine, ecstasy and GHB
      have risen significantly (1999-2002) in both locations, as have numbers of
      ecstasy tablets taken on a usual night. Substance use was associated positively
      with number of previous visits to Ibiza and new users were recruited into use
      while abroad (17.4 and 33.1 per 1000 people were introduced to cocaine and
      ecstasy use, respectively, in Ibiza). CONCLUSIONS: The emergence of international
      nightlife resorts increasingly links drug use abroad with that in individuals'
      countries of origin. Our results indicate that resorts such as Ibiza offer
      tourists the opportunity to increase levels of drug consumption and try different
      substances in an atmosphere conducive to experimentation. Patterns of
      recreational drug use in leading international resorts may help predict
      developments in drug use elsewhere and as such be an important tool in planning
      appropriate interventions.

PMID- 14651504
TI  - Areca quid chewing by Taiwanese adolescents: application of the Attitudes Social
      Influence Self-efficacy (ASE) model.
AB  - AIMS: To investigate the factors associated with areca quid-chewing behaviour
      using the Attitudes-Social influence-Self-efficacy (ASE) model as a theoretical
      framework. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: A total of
      400 students from a junior high school participated in the study in 2001 in Chia
      Yi city (Taiwan). MEASUREMENTS: Expectancy scales (for the attitude component of
      the ASE), a self-efficacy scale (for the self-efficacy component of the ASE) and
      a social norm scale (for the social influence component of the ASE) were
      utilized. These measures displayed good reliability and validity. FINDINGS: Forty
      seven students (11.75%) reported that they had tried chewing areca quid
      previously, eight of them practicing chewing it every day. Positive and negative
      expectancy (r = 0.43, r=- 0.20), self- efficacy (r = - 0.65), and subject social
      norm (r = 0.53) were significantly correlated with participants' intentions to
      chew areca quid. In a regression model, self-efficacy (beta = - 0.46, P < 0.001),
      social norm (beta = 0.22, P < 0.001), positive expectancy (beta = 0.18, P <
      0.001) and negative expectancy (beta = - 0.08, P = 0.040) all made independent
      contributions to predicting intentions to chew and explained 46.8% of the
      variance in areca quid-chewing behaviour. CONCLUSIONS: Areca quid chewing
      appeared to be linked to positive expectancy and social norms pertaining to areca
      quid chewing associated with adolescents. However, high negative expectancy and
      high self-efficacy encouraged contrary behaviour. The application of the ASE
      model as the scenario could improve our understanding of the intention of the
      areca quid chewing among these adolescents.

PMID- 14651505
TI  - Chronic depersonalization following illicit drug use: a controlled analysis of 40
      cases.
AB  - AIMS: To examine demographic and clinical features of a group of patients
      reporting chronic depersonalization (DP) following illicit drug use, and to
      assess whether depersonalization arising in these circumstances constitutes a
      distinct clinical syndrome. DESIGN: Case-control comparison using self-reports,
      standardized questionnaires and clinical assessments in a specialized clinic.
      SETTING: A tertiary referral depersonalization clinic and research unit
      affiliated to a psychiatric hospital and research centre. PARTICIPANTS: A total
      of 164 individuals with chronic DP symptoms who had been in contact with the
      clinic. Forty of these individuals related the onset of symptoms to an episode of
      illicit drug use. MEASUREMENTS: A wide range of demographic and clinical
      variables measured using questionnaires and standardized rating scales. FINDINGS:
      The drug-induced DP group were significantly younger and had a preponderance of
      males compared to the non-drug group. Certain clinical and phenomenological
      differences were found between these groups, but in general the groups are
      strikingly similar. This is reinforced by the fact that when the drug-induced
      group was compared with an age and sex-matched subset of the non-drug group,
      differences between groups largely disappeared. CONCLUSIONS: Drug-induced DP does
      not appear to represent a distinct clinical syndrome. The neurocognitive
      mechanisms of the genesis and maintenance of DP are likely to be similar across
      clinical groups, regardless of precipitants.

PMID- 14651506
TI  - Types of natural recovery from alcohol dependence: a cluster analytic approach.
AB  - BACKGROUND: Social capital and a low severity of alcohol-related problems have
      been focused upon to explain the processes of natural recovery from alcohol
      dependence. However, studies using control groups have not found significant
      differences in these variables. Subtypes of natural remission which might account
      for this inconsistency have only been described on grounds of qualitative data.
      AIMS: To identify subtypes of natural remitters using cluster analysis.
      PARTICIPANTS: One hundred and seventy-eight media-recruited natural remitters
      were interviewed personally. Several triggering mechanisms and maintenance
      factors of remission were assessed using standardized questionnaires. Based on
      age of onset and severity of dependence, adverse consequences from drinking,
      social pressure and social support, cluster analyses were performed. RESULTS:
      Cluster analyses yielded three groups of natural remitters: one cluster with a
      high severity of dependence, low alcohol-related problems and low social support
      ('low problems-low support'; n = 65), one group characterized by high severity of
      dependence, high alcohol-related problems and medium social support ('high
      problems-medium support'; n = 37), and a third group which consisted of subjects
      with high social support, late age of onset, low severity of dependence, and low
      alcohol-related problems ('low problems-high support'; n = 76). Cluster solutions
      were confirmed using discriminant analyses. Analyses of variance (ANOVAs)
      revealed further group differences on other triggering and maintaining factors of
      remission. CONCLUSIONS: Failure to identify specific pointers to natural recovery
      in previous research might be due to heterogeneous subgroups of natural
      remitters. In order to build a conceptual framework for understanding the
      processes of natural recovery, interactions of different independent variables
      should be considered.

PMID- 14651507
TI  - Patterns of over-the-counter nicotine gum use: persistent use and concurrent
      smoking.
AB  - AIMS: To examine the occurrence of persistent use (i.e. use beyond 12 weeks) and
      concurrent use of nicotine gum with cigarettes among consumers who purchase
      nicotine gum over-the-counter (OTC). DESIGN: Assessment of gum use was conducted
      in the context of a smoking cessation trial among smokers who purchased Nicorette
      gum and enrolled in the optional Committed Quitters smoking cessation program.
      Eligible participants were contacted by telephone 6 weeks and 12 weeks following
      their self-selected target quit date. Those who reported gum use at 12 weeks were
      contacted again at week 24. PARTICIPANTS: A total of 2655 current smokers who
      purchased nicotine gum and enrolled in a clinical efficacy trial of the Committed
      Quitters program. MEASUREMENTS: Detailed information on smoking and gum use,
      including frequency of use, amount used and reasons for use was obtained at each
      of the three follow-up assessments. FINDINGS: At the 24-week assessment, 6% of
      participants reported current use of nicotine gum (i.e. persistent use). Those
      engaging in persistent use averaged 4.7 (SD = 2.5) days of gum use per week and
      3.2 (SD = 3.5) pieces of gum per day. Sixty-six per cent of persistent users
      reported at week 24 that they were not currently smoking, and 67% of persistent
      users reported they were using gum to establish or maintain abstinence. At the 6
      , 12- and 24-week assessments, 14%, 10% and 2% of participants, respectively,
      reported current use of nicotine gum and current cigarette smoking (i.e.
      concurrent users). Those concurrent users reported at the 12-week follow-up that
      they did so an average of 4.4 (SD = 2.1) days per week, that they chewed an
      average of 2.6 (SD = 3.5) pieces of nicotine gum per day and that they smoked an
      average of 8.7 (SD = 8.6) cigarettes per day. CONCLUSION: Extended use of
      nicotine gum is rare. Concurrent use with cigarettes is uncommon. In both cases,
      the amount of gum use is small. OTC marketing of nicotine gum does not appear to
      have increased use contrary to labeling nor resulted in patterns of use that
      should warrant clinical or public health concerns.

PMID- 14651508
TI  - The alcohol-tobacco relationship: a prospective study among adolescents in six
      European countries.
AB  - AIM: This study examined the earliest stages in drug involvement, in terms of the
      relationship between alcohol and tobacco use, among adolescents from six European
      countries (Denmark, Finland, the Netherlands, Portugal, Spain and the United
      Kingdom). International, gender and age differences were studied. DESIGN, SETTING
      AND PARTICIPANTS: A large international sample of European adolescents (n =
      10170, mean age = 13.3 years) was followed longitudinally. Data were gathered in
      the autumn terms of 1998 and 1999 by means of self-administered questionnaires.
      MEASURES: Adolescents' self-reports on smoking and alcohol behaviour were used.
      Both behaviours were classified into two categories, that of adolescents who had
      never used the substance and that of those who had used the substance at least
      once in their lives. Logistic regression was used to determine which substance
      was the best predictor of the subsequent use of the other substance. FINDINGS:
      Alcohol use and tobacco use were found to be associated with each other
      reciprocally. Results revealed that in Europe as a whole, tobacco use predicted
      subsequent alcohol use better than the converse. However, for Dutch girls,
      alcohol use predicted subsequent smoking behaviour better than the converse.
      CONCLUSION: The findings suggest that the development of alcohol and tobacco use
      patterns are closely related, but the order of progression is not universal and
      may reflect cultural factors.

PMID- 14651509
TI  - Cigarette consumption and socio-economic circumstances in adolescence as
      predictors of adult smoking.
AB  - AIM: To investigate effects of cigarette consumption level and socio-economic
      circumstances during adolescence on adult smoking. METHODS: 1958 British birth
      cohort (all births 3-9 March 1958). Logistic regression used to predict (i)
      smoking at 41 years and (ii) persistent smoking (at 23, 33 and 41 years) from
      cigarette consumption and socio-economic circumstances at 16 years, indicated by
      social class and educational qualifications. RESULTS: Of 6537 subjects with full
      smoking history, 30% smoked at 16 years, 23% smoked at 41 years and 19% smoked at
      23, 33 and 41 years (persistent smokers). Heavier smokers at 16, 23 and 33 years
      were more likely to smoke at 41 years than lighter smokers. The odds ratio (OR)
      of smoking at 41 years was 2.5 for men and 3.0 for women who smoked >/=60
      cigarettes/week at age 16, relative to <20 cigarettes/week. Subjects from manual
      social backgrounds and those with no qualifications had elevated risks of being a
      smoker at 41 years or a persistent smoker. These effects were robust to
      adjustment for adolescent consumption level (e.g. adjusted OR for no
      qualifications was 3.8). However, adolescent consumption level modified the
      effect of educational achievements. Among lighter adolescent smokers, those
      gaining higher qualifications had lower prevalence of smoking at 41 years (16%)
      than men with no qualifications (83%); among heavier adolescent smokers,
      prevalence was more similar for subjects with higher (56%) and no qualifications
      (69%). CONCLUSIONS: Socio-economic background appears to influence adult smoking
      behaviour separately from adolescent cigarette consumption which is a recognized
      measure of nicotine dependence. There was some evidence that effects of early
      nicotine dependence are modified by educational achievements.

PMID- 14651510
TI  - Research and the alcohol industry.

PMID- 14651512
TI  - Heroin addiction and the capacity for consent: a reply to Charland.

PMID- 14651517
TI  - Human uterine leukocytes and pregnancy.
AB  - In human pregnancy, the embryo implants into the specialized mucosal wall of the
      uterus (decidua) and the placenta starts to form. Cells from the placenta
      (trophoblasts) invade into the uterine mucosa in order to open up maternal
      uterine arteries to ensure an adequate supply of blood to the developing fetus.
      The trophoblasts have a unique immunological phenotype compared to most cells
      especially with regard to their expression of major histocompatibility complex
      (MHC) antigens. On the other side of the interaction, the uterine mucosa
      (endometrium) differentiates in preparation for implantation. One of the changes
      that takes place is the appearance in the endometrium of a large number of
      maternal leukocytes in the final part of the menstrual cycle. If pregnancy
      ensues, these leukocytes continue to increase in number and are found in close
      contact with trophoblasts. The composition of this population of maternal immune
      cells is unusual compared to that seen at other mucosal sites. A lot of research
      has focused on whether maternal T-cell responses are suppressed or modified
      during pregnancy. Research has also concentrated on the specialized uterine
      natural killer (NK) cells, which are found in the decidua in large numbers during
      early pregnancy. These uterine NK cells have been shown to express receptors for
      trophoblast MHC antigens, but their role in pregnancy is still mysterious. The
      purpose of this review is to give an overview of what is known about the
      immunology at the implantation site and also to provide an update of some of the
      most recent findings in this field.

PMID- 14651518
TI  - A NOTCH4 association with multiple sclerosis is secondary to HLA-DR*1501.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) with supposedly autoimmune features known to be associated with a
      specific HLA DR-DQ haplotype (DR15, DQ6, or
      HLDRB1*1501,DRB5*0101,DQA1*0102,DQB1*0602). We have previously reported that the
      associated haplotype extends to HLA-B and described an independent association
      with HLA-A alleles in MS. Owing to a complex situation with extensive linkage
      disequilibria, it is still unclear whether classical HLA genes are responsible or
      whether associations may be due to other genes in this region. Here, we analyzed
      an association in MS with the NOTCH4 and TNFalpha (tumor necrosis factor-alpha)
      genes, located between the HLA-DRB1 gene and the HLA-A gene. For NOTCH4, located
      0.4 Mb telomeric to HLA-DRB1, an SNP at position -25 and a trinucleotide repeat
      were investigated in 181 MS patients, and 180 controls also typed P = 0.027 for
      HLA-DRB and HLA-A. A modest association was observed (OR = 3.44) with the C-25
      allele. However, two-locus analysis revealed that this association was secondary
      to the classical association with HLA-DRB1. For TNF, located 0.7 Mb telomeric of
      NOTCH4, SNPs at positions -308 and -238 were studied in the same dataset. We
      found no association between these TNFalpha gene polymorphisms and MS in this
      dataset, although there was linkage disequilibrium (LD) between DRB1 and TNF and
      between HLA-A and TNF. We conclude that alleles of the NOTCH4 and TNFalpha genes
      are unlikely to be of importance for the susceptibility to MS, although specific
      alleles of these genes are often carried on the same haplotype as DR15, DQ6.

PMID- 14651519
TI  - Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic
      lupus erythematosus in Chinese: a common susceptibility gene in the Asian
      populations.
AB  - The association of Fcgamma receptor (FcgammaR) polymorphisms with systemic lupus
      erythematosus (SLE) has been demonstrated in various populations; however, the
      results have been inconsistent. We recently identified a single-nucleotide
      polymorphism encoding a non-synonymous substitution, Ile232Thr (I232T), of FCGR2B
      and its association with SLE in Japanese and in Thais. Multiple functional
      FcgammaR genes with polymorphisms (FCGR2A, FCGR2B, FCGR3A, and FCGR3B) cluster in
      1q23, and some of them are in linkage disequilibrium (LD). To differentiate
      contributions from multiple-linked loci, comparison of different populations may
      provide useful information. In this study, we analyzed the above four FCGR
      polymorphisms of the Chinese patients and controls for the association with SLE.
      FCGR2A-H131R, FCGR2B-I232T, FCGR3A-F176V, and FCGR3B genotypes were determined in
      167 Chinese patients with SLE and 129 healthy controls. Association was examined
      using case-control analysis. Allele frequencies of FCGR2B-232T and FCGR3A-176F
      were significantly increased in SLE [odds ratio (OR) = 1.67 and OR = 1.41,
      respectively]. Interestingly, while these alleles had a tendency of positive LD
      in the controls, FCGR2B-232T was in positive association with FCGR3A-176V in SLE,
      suggesting that these two alleles were associated with SLE in an independent
      manner. Comparison between SLE with and without nephritis indicated significant
      association of FCGR2B-232T with nephritis (OR = 2.65). When the present results
      were combined with our previous data on the Japanese and the Thais using meta
      analytic methods, highly significant and independent association was observed for
      FCGR2B and FCGR3A genotypes. These results strongly suggested that FCGR2B is a
      common susceptibility factor to SLE in the Asians.

PMID- 14651520
TI  - Genetic variants in the tumor necrosis factor receptor II gene in patients with
      multiple sclerosis.
AB  - Common genetic variants have been shown to influence disease susceptibility,
      disease course, or both in multiple sclerosis (MS). Several studies have
      suggested a role for tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis
      of MS. Recently, it has been reported that the TNF receptor (TNFR) II plays an
      essential role in the pathology and progression of experimental autoimmune
      encephalomyelitis, an animal model of MS. To investigate whether TNFR II
      polymorphisms influence susceptibility and/or clinical progression of MS, genomic
      DNA of 321 samples of the Austrian Genetics in MS study group and DNA of 174
      platelet donors, who served as healthy controls, were genotyped for five
      polymorphic sites in the TNFR II gene: exon 6 nucleotide (nt) 676*T-->G, exon 6
      nt 783*G-->A (both are associated with non-conserved amino acid substitution),
      exon 10 nt 1663*G-->A, exon 10 nt 1668*T-->G, and exon 10 nt 1690*T-->C (all of
      which are located in the 3' non-coding region of the gene). We found a
      significant association between exon 10 nt 1668*T-->G polymorphism and
      susceptibility to MS. The other investigated nucleotide substitutions were not
      associated with susceptibility to or clinical parameters in MS.

PMID- 14651521
TI  - Eleven human platelet systems studied in the Vietnamese and Ma'ohis Polynesian
      populations.
AB  - The frequencies of human platelet antigens (HPA) are variable among different
      ethnic groups. Platelet phenotyping and genotyping in different populations are
      important to the clinical implications of antiplatelet alloimmunization. No
      report on HPA prevalence has been published concerning the Vietnamese Kinh and
      Ma'ohis Polynesian populations. Recent anthropological and genetic marker studies
      suggest that these two groups have a common origin in East Asia, so we have
      conducted a combined study concerning the frequency of HPA-1 to HPA-11w systems
      (excluding HPA-8w) and Gov in these two populations. The results demonstrate a
      similar pattern of prevalence between Ma'ohis and most of the Asian populations.
      However, it should be noted that the frequency of HPA-2 is closer to northern
      Caucasian frequencies than to Asian frequencies. The population of Kinh shows an
      HPA distribution that is closer to the Chinese population than to the
      northeastern Thais except for HPA-3, closer to the Indonesian population. Given
      HPA-3 gene frequency distribution fetomaternal incompatibility could occur more
      frequently with the risk of alloantibody production.

PMID- 14651522
TI  - Chemokine gene polymorphisms associate with gender in patients with uveitis.
AB  - Uveitis is an inflammatory condition of ocular tissue characterized by leukocyte
      infiltration, tissue damage, and decreased visual acuity. Chemokines have been
      implicated in the pathogenesis of uveitis. Polymorphisms in the genes encoding
      chemokines have been described as affecting chemokine production or function. We
      analyzed the frequency of single-nucleotide polymorphisms (SNPs) in genes
      encoding CCL2 (-2518 and -2076) and CCL5 (-403 and -28) in patients with Behcet's
      disease (BD), a systemic form of uveitis, and patients with retinal vasculitis
      (RV), an organ-specific form of disease. We report that there was no association
      between any SNP and disease. However, when segregated on the basis of gender the
      CCR5 -403 AA genotype was only found in male patients with BD. Similarly, CCL2
      genotypes 1/2 were predominant in males, while genotype 4 was significantly
      associated with disease in female patients with BD. Differences in disease
      symptoms and severity between males and females have been described in BD and
      gender-specific genetic differences in chemokine gene function may be involved.

PMID- 14651523
TI  - Production and the characterization of monoclonal antibody against CD43, K06.
AB  - A monoclonal antibody against human CD43 has been developed and designated as
      K06. Its reactivity in the lymphoid organs was different from that of known anti
      CD43 monoclonal antibodies suggesting that this may recognize a novel epitope of
      human CD43 molecule. The CD43 epitope detected by anti-K06 monoclonal antibody
      was highly expressed in cortical thymocytes, platelets, and myeloid cells of
      normal peripheral blood, and its reactivity was comparable to that of known anti
      CD43 monoclonal antibodies. However, the density of this epitope was lower in the
      medullary thymocytes. Biochemical studies indicated that anti-K06 monoclonal
      antibody could recognize glycosylated moiety of CD43 antigen. The expression
      profile of anti-K06 monoclonal antibody in several cell lines was somewhat
      different from that of known anti-CD43 antibodies. In addition, CD43 ligation
      through the K06 epitope appeared to induce apoptosis in human leukemic cell line,
      Molt-4. We therefore assume that K06 epitope of human CD43 might have some role
      in T-cell development.

PMID- 14651524
TI  - Polymorphisms of toll-like receptor 2 and 4 genes in rheumatoid arthritis and
      systemic lupus erythematosus.
AB  - Human toll-like receptors (TLRs) participate in the innate response and signal
      the activation of adaptive immunity. Therefore, these TLRs may be important in
      autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE). We investigated, by using a polymerase chain reaction
      restriction-fragment length polymorphism method, the possible association between
      the polymorphisms of TLR2 (Arg677Trp and Arg753Gln) and TLR4 (Asp299Gly and
      Thr399Ile) genes with the susceptibility or severity of RA and SLE. Our study
      population consisted of 122 patients with SLE, 224 patients with RA, and a
      control group of 199 healthy individuals. The TLR2 polymorphisms were very rare
      in our population; no individual carrying the TLR2-Arg677Trp polymorphism was
      observed, whereas the TLR2-Arg753Gln polymorphism was present in only 1% of the
      total population. We found no statistically significant differences in the TLR4
      Asp299Gly and the TLR4-Thr399Ile genotype or allele distribution between SLE
      patients, RA patients, and control individuals. Similarly, no association was
      found with any of the demographic and clinical parameters tested either in RA or
      in SLE patients. In conclusion, a case-control study was used to analyze, for the
      first time, the influence of TLR2 and TLR4 gene polymorphism on the
      predisposition and clinical characteristics of SLE and RA but provided no
      evidence for association of TLR2 or TLR4 gene polymorphism with either disease in
      the population under study.

PMID- 14651525
TI  - HLA DQA1 genes generate multiple transcripts by alternative splicing and
      polyadenylation of the 3' untranslated region.
AB  - Regulation of the human leucocyte antigen (HLA) class II genes expression is an
      important field in immunology, because these molecules play a crucial role in the
      function of the immune system. HLA DQ genes expression is a complex phenomenon
      regulated at both transcriptional and post-transcriptional levels. In this study,
      we have investigated the post-transcriptional mechanisms accounting for alleles
      dependent length polymorphism of DQA1 mRNA. We have first sequenced the genomic
      DNA encoding the 3' untranslated region (UTR) of DQA1 *0101, *0102, *0103, *0201,
      *0301, *0401, and *0501 alleles. We have identified two competing splicing sites:
      a unique splicing donor site AG/GTA located 20 nucleotides downstream from the
      stop codon associated to two spliced acceptor sequences, approximately 165 and
      approximately 370 nucleotides downstream. In addition, three polyadenylation
      signals have been identified, respectively, at approximately 475, approximately
      795, and approximately 855 nucleotides downstream from the stop codon.
      Subsequently, we have analyzed mRNAs derived from DQA1 alleles in homozygous B
      lymphoblastoid cell lines by reverse transcriptase-polymerase chain reaction. We
      show that allele-dependent length polymorphism of DQA1 mRNA-3' UTR results from a
      combination of differential splicing and alternative polyadenylations. Four mRNA
      isoforms (two spliced variant cleaved at two distinct polyadenylation sites) were
      detected in DQA1 *0101, *0102, and *0103 homozygous cell lines, and six mRNA
      species (three spliced variant cleaved at two polyadenylation-sequence signal)
      were generated by the other four alleles. Possible advantages for cells to
      generate multiple transcripts previously undetected are discussed.

PMID- 14651526
TI  - The human leukocyte antigen genotype has a modest effect on the insulin gene
      polymorphism-associated susceptibility to type 1 diabetes in the Finnish
      population.
AB  - In addition to the known human leukocyte antigen (HLA)-associated risk,
      polymorphisms of insulin gene region show association with type 1 diabetes. We
      analyzed possible interactions between the HLA class II genotypes and -2221 MspI
      (insulin) INS gene polymorphism in Finnish population, using a series of 1331
      diabetic children and 2222 healthy newborns. C/C genotype was increased among
      diabetic children compared to the controls (83.2 vs 70.1%). This genotype was
      slightly more common in diabetic children with low or moderate HLA-associated
      risk than in those with high risk, but INS gene effect was clear in all major HLA
      risk genotypes and, thus, can be used as an additional risk prediction marker,
      irrespective of HLA genotypes.

PMID- 14651527
TI  - TNF-alpha promoter polymorphisms and extended HLA and TNF-alpha haplotypes in
      Koreans based on 100 families.
AB  - We investigated five single-nucleotide polymorphism (SNP) sites of tumor necrosis
      factor-alpha (TNF-alpha) promoter, the distribution of five-locus TNF-alpha
      haplotypes, and extended human leukocyte antigen (HLA)/TNF-alpha haplotypes in
      200 parents from 100 unrelated Korean families. TNF-alpha SNPs were typed using
      polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and
      PCR restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies
      of -1031C, -863A, -857T, -308A, and -238A alleles were 0.185, 0.145, 0.140,
      0.060, and 0.040, respectively. The allele frequencies in Koreans were similar to
      those of Japanese. A total of five TNF-alpha haplotypes (-1031/-863/-857/-308/
      238) were detected in 196 parents: TCCGG (frequency 0.617), CACGG (0.143), TCTGG
      (0.143), TCCAG (0.061), and CCCGA (0.036). Five most common extended HLA/TNF
      alpha haplotypes (frequencies >0.020) accounted for 16% (63/392) of the total
      haplotypes. A total of 223 HLA haplotypes and 239 HLA/TNF-alpha haplotypes were
      detected, indicating that most HLA haplotypes are exclusively associated with
      particular TNF-alpha haplotypes.

PMID- 14651528
TI  - Five newly identified HLA alleles: A*0310, A*2907, B*4435, Cw*0206, Cw*0506, and
      confirmation of A*3106, B*3924, Cw*0314, DRB1*0322, and DRB1*1433 alleles.
AB  - A number of HLA alleles have been newly identified. This concerns HLA-A*0310,
      A*2907, B*4435, Cw*0206, Cw*0506, of which Cw*0206 was found in three unrelated
      individuals, all B*4002 positive. Some other alleles are also presented but
      confirm earlier detected sequences: A*3106, Cw*0314, DRB1*0322, and DRB1*1433.
      Moreover, we identified B*3924 in a bone marrow transplant recipient and in five
      of six unrelated stem cell donors, selected for this patient. In all cases,
      B*3924 was found on a haplotype combining A*0201, B*3924, Cw*0701, and DRB1*1303.
      The observation of this extended haplotype is of importance for the selection for
      stem cell transplantation. Cells expressing B*3924 and B*4435 were typed by
      serology as B39 and B44, respectively. Cells expressing HLA-A*0310 do not express
      A3 but type as A-Blank.

PMID- 14651529
TI  - A novel HLA-A allele: A*0257.
AB  - A novel human leucocyte antigen-A*02 (HLA-A*02) allele was detected by reference
      strand-mediated conformation analysis (RSCA) of a DNA sample from a Tarahumara
      individual. Direct sequencing of HLA-A locus polymerase chain reaction products
      identified a mutation in one of the alleles. Cloning and sequencing confirmed the
      presence of a new allele, A*0257 which differed from A*0206 by two nucleotides at
      positions 355 and 362, inducing changes in residues 95 and 97, respectively,
      within the peptide-binding site. Those changes suggest that allele A*0257 may
      have resulted from an intralocus recombination event.

PMID- 14651530
TI  - Rapid detection of all HLA-B*27 alleles (B*2701-B*2725) by group-specific
      polymerase chain reaction.
AB  - Human leucocyte antigen-B*27 is strongly associated with a number of rheumatic
      diseases, including ankylosing spondylitis and reactive arthritis. Targeted
      detection of the B*27 group by molecular methods is hampered by the extreme
      heterogeneity of the serological B*27 group. Here, we describe a simple, rapid
      sequence-specific primer-based method for detection of all 28 B*27 alleles
      defined to date. The method involves an initial screening with two sequence
      specific polymerase chain reactions (PCRs), which has to be followed by two
      additional PCR amplifications in samples carrying a few rare subtypes of B*27,
      B*4202 or B*7301. The described protocol should be useful for laboratories
      involved in diagnostics and research of rheumatoid diseases.

PMID- 14651531
TI  - Identification of two novel HLA class II alleles, DQB1*030503 and DRB1*0447.
AB  - Two novel human leukocyte antigen (HLA) class II alleles have been identified in
      routine typing of bone marrow donors for the Australian Bone Marrow Donor
      Registry in Sydney, Australia. Sequence analysis of exon 2 of both the DQB1 and
      DRB1 genes revealed the novel polymorphism. A silent substitution of G to A at
      nucleotide position 210 has been identified for the DQB1*030503 allele when
      compared to the closest matched allele, DQB1*030501. There is no associated amino
      acid difference between the translated products of the two alleles. The second
      new allele is a variant of the DRB1 gene. The DRB1*0447 allele was identified
      with three nucleotide substitutions compared to the closest matched allele
      DRB1*0436. There is a silent mutation at nucleotide position 303, G to C and two
      substitutions at adjacent nucleotide positions 344 and 345, T to G and G to T,
      respectively. The latter two substitutions result in an amino acid change from
      valine to glycine at position 86, implicating a different specificity and
      affinity of antigen binding.

PMID- 14651532
TI  - Nomenclature for factors of the HLA system, update July 2003.

PMID- 14651533
TI  - Nomenclature for factors of the HLA system, update August 2003.

PMID- 14651534
TI  - Spontaneous platelet aggregation in Kawasaki disease using the particle counting
      method.
AB  - BACKGROUND: Platelet aggregation is generally measured by the optical density
      method. This method is not very sensitive in detecting platelet activation
      because of the poor correlation between the formation of platelet aggregates and
      light transmission, and inability to detect small platelet aggregates. Recently,
      a new method was developed that detects small platelet aggregates formed in the
      early phase of platelet aggregation by means of a particle counting technique
      using light scattering. METHODS: The present study used the particle counting
      method to measure spontaneous platelet aggregation (SPA) produced by agitation
      with a stirrer bar without agonists in patients with Kawasaki disease (KD) and
      children's thrombotic disease, and compared the results with the conventional
      optical density method. RESULTS: Using the particle counting method,
      significantly higher SPA rates were found before treatment than in healthy adults
      and at the other stages of treatment. A similar tendency was noted with the
      optical density method; however, the positive rate of SPA was significantly
      higher with the particle counting method in each stage except the second stage,
      which was the period from the start of gamma-globulin therapy to 20 days.
      CONCLUSION: These results indicate that enhanced platelet aggregation is noted at
      a high frequency before treatment of KD and that the particle counting method is
      superior to the optical density method in detecting enhanced platelet
      aggregation.

PMID- 14651535
TI  - Ketotic hypoglycemia in patients with allergic diseases.
AB  - BACKGROUND: Ketotic hypoglycemia is the most common cause of recurrent
      hypoglycemia in early childhood but its etiology is poorly understood.
      Elimination diets have been used for the prevention or treatment of some allergic
      diseases; however, these diets entail a risk to the normal nutrition and growth
      of children. The present study investigated whether elimination diets are related
      to the occurrence of ketotic hypoglycemia. METHODS: The prevalence of allergy
      treated with elimination diet therapy was retrospectively investigated in 18
      patients with ketotic hypoglycemia seen in Yamaguchi University Hospital between
      January 1995 and September 1999. Data were gathered by reviewing the patients'
      medical charts. RESULTS: Ten (55.6%) of 18 patients with ketotic hypoglycemia had
      allergic diseases. Six (60%) of the patients had been treated with strict
      elimination diets and the others were on incomplete elimination diets for the
      prevention of allergy. The ketotic hypoglycemia patients with allergic diseases
      had experienced fewer pre-existing infectious diseases than those without
      allergic diseases. CONCLUSIONS: Patients with allergic diseases treated with
      elimination diets have a relatively high tendency towards developing ketotic
      hypoglycemia. They might have a lower capacity to tolerate fasting due to their
      excessive avoidance of many foods, even during periods when they are not
      undergoing strict elimination diets.

PMID- 14651536
TI  - Antenatal steroid treatment prevents severe hyperkalemia in very low-birthweight
      infants.
AB  - BACKGROUND: Hyperkalemia is seen quite often in very low-birthweight (VLBW)
      infants and concentrations sometimes become high enough to cause cardiac
      arrhythmia. The purpose of the present study was to identify factors that
      increase serum concentrations of potassium in VLBW infants. METHODS:
      Retrospective comparative analysis was performed on 140 VLBW infants who had been
      admitted to the Toho University Perinatal Center between January 1993 and
      December 1999 and needed mechanical ventilation for respiratory distress. Serum
      concentrations of potassium at 24 and 48 h of age were compared in two groups of
      infants, those whose mothers did and did not receive antenatal steroid treatment.
      Risk factors for severe hyperkalemia were analyzed by multiple linear regression
      models and Pearson's partial correlation analysis. RESULTS: Antenatal steroid
      treatment reduced serum potassium concentrations significantly at 24 and 48 h, as
      well as the incidence of cardiac arrhythmia and necessity for glucose insulin
      treatment for severe hyperkalemia. Multiple linear regression showed the serum
      potassium concentration at 24 h of age was associated with antenatal steroid
      hormone treatment, 24 h fluid intake volume, serum sodium concentrations at 24 h,
      gestational weeks and sampling site. Serum concentration of potassium at 48 h of
      age was associated with blood urea nitrogen, gestational week, serum sodium
      concentration at 48 h of age and fluid intake between 24 and 48 h of age. Urine
      output volume and serum creatinine concentrations were not correlated with
      potassium concentrations at either age. CONCLUSION: Antenatal steroid hormone
      treatment can reduce early hyperkalemia in VLBW infants and also the incidence of
      cardiac arrhythmia and the use of glucose insulin treatment.

PMID- 14651537
TI  - Evaluation of change of cerebral circulation by SpO2 in preterm infants with
      apneic episodes using near infrared spectroscopy.
AB  - BACKGROUND: In the neonatal intensive care unit (NICU), hemodynamics in very low
      birthweight infants are generally examined for oxygen saturation (SpO2), heart
      rate, respiration rate, and blood pressure. The present study examined how
      changes in cerebral circulation in preterm infants can be evaluated by the SpO2
      monitoring method with near infrared spectroscopy (NIRS) to detect the cerebral
      circulation. METHODS: The study was conducted in 11 low-birthweight neonates with
      a mean weight of 1252 g (940-1948 g), mean post-conceptional age of 28.9 weeks
      (28-31 weeks) and in whom a total of 145 apneic episodes were examined. Changes
      in cerebral circulation at the apneic attack were evaluated by two parameters of
      Delta HbD ( micro mol/L) for reduction in cerebral oxygenation and Delta cHb
      (mL/100 g brain) for variation in cerebral blood volume using the near infrared
      spectroscopy (NIRS). RESULTS: There was a tendency for a reduction in cerebral
      oxygenation and a change in cerebral blood volume as SpO2 was reduced. In the
      event of apneic attacks where SpO2 was reduced to <85%, cerebral oxygen
      saturation was extensively reduced. In addition, cerebral blood volume was also
      greatly changed when the SpO2 was reduced to <85%, and changed further still when
      SpO2 was reduced again to < or =75%. CONCLUSION: Reduction in SpO2 (<85%) was
      suggested to be an effective indication to changes in cerebral circulation. In
      the case of apneic attacks where SpO2 was < or =85%, the cerebral circulation in
      preterm low-birthweight neonates was extensively changed and, therefore,
      attention should be paid to changes in the concentration of SpO2 when managing
      apnea of prematurity in NICU.

PMID- 14651538
TI  - Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in
      preterm infants.
AB  - BACKGROUND: Patent ductus arteriosus (PDA) is commonly found in very low
      birthweight (VLBW) infants. The presence of respiratory distress syndrome (RDS)
      is also associated with increased frequency of significant PDA. Intravenous
      indomethacin has been used to treat and to prevent PDA in premature infants since
      1976. However, concern remains regarding the safety of indomethacin, which
      affects renal, gastrointestinal and cerebral perfusion. Intravenous ibuprofen has
      recently been used to treat and to prevent PDA premature infants with PDA without
      reducing cerebral blood flow or affecting intestinal or renal hemodynamics. The
      aim of the present study is to compare intravenous ibuprofen and indomethacin
      with regard to efficacy and safety for the early treatment of PDA in preterm
      infants. METHODS: A total of 63 preterm infants with RDS who had a birthweight of
      < or =1500 g and gestational age of < or =32 weeks, were enrolled in the present
      study. All patients were treated with nasal continuous positive airway pressure
      with additional oxygen supply in inspired air>30%, or with mechanical
      ventilation. The patients' serum platelet counts were>100,000/uL, and serum
      creatinine values were <1.5 mg/dL. There were no 3-4 grade intraventricular
      hemorrhages before randomization, and all patients were aged 2-7 days and had
      echo-cardio-graphic evidence of significant PDA. Patients were randomized into
      two groups: the first group of neonates (group A, n = 32) received intravenous
      ibuprofen lysine 10 mg/kg, followed by 5 mg/kg after 24 and 48 h; the second
      group (group B, n = 31) received intravenous indomethacin 0.2 mg/kg every 12 h
      for three doses. RESULTS: Patent ductus arteriosus closed in 27 patients from the
      ibuprofen group (84.4%) and in 25 patients from the indomethacin group (80.6%).
      PDA reopened in three patients from the ibuprofen group (9.4%) and in three
      patients from the indomethacin group (9.7%). One patient in the ibuprofen group
      and two patients in the indomethacin group required ductal ligation. Serum
      creatinine and blood urea nitrogen (BUN) concentrations were lower in the
      ibuprofen group than in the indomethacin group. Urine output and creatinine
      clearance values were higher in the ibuprofen group than in the indomethacin
      group. CONCLUSIONS: Ibuprofen therapy is as efficacious as indomethacin for the
      treatment of PDA in preterm infants. Infants treated with ibuprofen have higher
      creatinine clearance and urine output and lower serum creatinine and BUN values
      than infants treated with indomethacin.

PMID- 14651539
TI  - Effect of beraprost sodium on pulmonary vascular resistance in candidates for a
      Fontan procedure: a preliminary study.
AB  - OBJECTIVE: Although long-term prostacyclin(PGI2) therapy in patients with severe
      pulmonary hypertension (PH)reduces pulmonary vascular resistance (PVR), there
      have been no reports on its therapeutic effects in patients with mild PH. We
      investigated the chronic effect of beraprost sodium (BPS), an oral PGI2 analog,
      in children with mild PH. METHODS: We studied 20 patients who were destined for a
      Fontan procedure with a mean pulmonary arterial pressure(PAP) of>20 mmHg and/or
      PVR of>3.0 Wood units. Both the PAP and the PVR in these cases were too high for
      patients to undergo a successful Fontan procedure. Seven patients received BPS
      (PG group) and 13 did not (control group). All patients underwent repeat cardiac
      catheterization to examine pulmonary hemodynamics. RESULTS: In the PG group, the
      pulmonary-to-systemic flow ratio (Qp/Qs) did not change after BPS
      administration(1.1 +/- 0.6 vs 1.3 +/- 0.9);however, the mean PAP decreased
      significantly (25.3 +/- 8.2 vs 19.9 +/- 6.5 mmHg; P < 0.05),as did PVR (3.7 +/-
      1.3 vs 2.3 +/- 0.9 Wood units; P < 0.05), whereas the pulmonary artery (PA) index
      increased significantly (312 +/- 136 vs 375 +/- 165; P < 0.05). In the control
      group, the mean PAP decreased significantly (24.9 +/- 4.7 vs 19.8 +/- 6.3 mmHg; P
      < 0.05)and the PA index increased significantly (295 +/- 72 vs 362 +/- 114; P <
      0.05). No significant changes in Qp/Qs (1.5 +/- 0.8 vs 1.4 +/- 0.6)or PVR (2.9 +/
      1.3 vs 2.5 +/- 0.8 Wood units) were observed. CONCLUSION: We conclude that long
      term BPS administration probably reduces PVR in potential candidates for a Fontan
      procedure with mild PH. This treatment would reduce the risks associated with the
      Fontan procedure and would also improve its outcome.

PMID- 14651540
TI  - Tolmetin and salicylate therapy in acute rheumatic fever: Comparison of clinical
      efficacy and side-effects.
AB  - BACKGROUND: The arthritis of rheumatic fever is very responsive to treatment with
      salicylates, but there are many adverse reactions, especially hepatotoxicity, due
      to aspirin (acetylsalicylic acid) therapy. These side-effects change the course
      and duration of rheumatic fever. Other non-steroidal anti-inflammatory drugs may
      be equally effective, although no reports are available. METHODS: We studied 72
      patients with rheumatic fever who were admitted to Dr Sami Ulus Children's
      Hospital between 1995 and 1999. Twenty patients with arthritis were treated with
      tolmetin (25 mg/kg per day; group I) and 52 patients with arthritis and/or mild
      carditis were put on aspirin therapy (75-100 mg/kg per day) for 4-6 weeks (group
      II). Arthritis had disappeared at the same time in both the aspirin and tolmetin
      groups (P = 0.675). RESULTS: The erythrocyte sedimentation rates of patients upon
      admission, at the first week and at the end of therapy were not different in the
      two groups (P > 0.05). No adverse effect of tolmetin therapy was observed,
      whereas side-effects of salicylate were observed in 19 patients (36.5%) in the
      aspirin group. Hepatotoxicity, gastric irritation and salicylism were found in
      16, four and three patients, respectively. Renal toxicity and Reye syndrome were
      not demonstrated. Because of these side-effects of aspirin, therapy had to be
      stopped for 10-20 days and the duration of hospitalization in this group was
      lengthened unnecessarily. CONCLUSION: Tolmetin was safe and effective treatment
      for arthritic rheumatic fever patients without carditis. Tolmetin can be used
      particularly in patients who cannot tolerate aspirin.

PMID- 14651541
TI  - Effect of mass immunization against influenza encephalopathy on mortality rates
      in children.
AB  - BACKGROUND: Since the Japanese influenza vaccination program for school children
      was terminated in 1994, a steep rise has been noted in the number of young
      children reported with fulminant influenza and influenza associated with acute
      encephalopathy/encephalitis. The purpose of the present study was to interpret
      and clarify the effect of mass influenza vaccination on mortality of Japanese
      children, aged <19 years, with influenza and influenza-associated acute
      encephalopathy/encephalitis. METHODS: The authors examined the distribution of
      mortality rates of children in Japan aged <19 years with influenza during 1950
      2000, influenza associated with central nervous system (CNS) signs in the period
      1950-1978, and the estimated cases of influenza associated with acute
      encephalopathy/encephalitis in the period 1987-2000. RESULTS: Total influenza
      mortality among children aged <19 years has increased since 1990, with children
      aged <4 years after 1994 being the worst affected. The mean values of mortality
      rates of influenza associated with central nervous system signs during 1963-1978
      and the estimated mortality of children aged <9 years during 1979-1994 were
      significantly lower than in some years before 1962, and after 1995 (P < 0.05).
      The annual mortality rates of influenza-associated acute
      encephalopathy/encephalitis during 1995-2000 were significantly higher than the
      expected mortality of influenza associated with central nervous system signs in
      children aged <14 years (P < 0.05). CONCLUSION: The results of the present study
      suggest that mass immunization of school-aged children reduced the mortality rate
      from influenza-associated acute encephalopathy/encephalitis in children less than
      9 years of age.

PMID- 14651542
TI  - Relationship between fluvoxamine and stress barometer for nocturnal enuresis.
AB  - BACKGROUND: It has been reported recently that fluvoxamine (a selective serotonin
      reuptake inhibitor) is effective and safe for children with monosymptomatic
      nocturnal enuresis (MNE). However, the exact mechanism by which fluvoxamine is
      beneficial in the treatment of MNE remains unknown. One possibility is that it
      controls emotional stress. METHODS: We divided children with MNE into primary MNE
      (n = 40) and secondary MNE (n = 7). We measured urinary 17-hydroxycorticosteroids
      (17-OHCS) and 17-ketosteroid sulfates (17-KS-S) as a stress barometer in children
      with MNE to evaluate adaptation to emotional stress before and during fluvoxamine
      treatment. We initially administered fluvoxamine at a dose of 25 mg at bedtime.
      If patients remained incontinent after 3 weeks, we increased the dose to 50 mg.
      RESULTS: Fluvoxamine was effective in 26 of 28 children (93%) with primary MNE
      and an abnormality of the stress barometer and in six of six children (100%) with
      secondary MNE and an abnormality of the stress barometer. Fluvoxamine was
      effective in only six of 12 children (50%) with primary MNE and normality of the
      stress barometer and was not effective in one child with secondary MNE and
      normality of the stress barometer. CONCLUSIONS: The stress barometer is useful
      clinically for evaluating the therapeutic effect of fluvoxamine for children with
      MNE.

PMID- 14651543
TI  - Clinical features of infants with subependymal germinolysis and choroid plexus
      cysts.
AB  - BACKGROUND: Periventricular cysts are not rare findings in neonates. However,
      they are sometimes associated with serious clinical complications, such as
      congenital viral infections and anomalies. METHODS: We performed a retrospective
      follow-up study on newborns who had periventricular cysts on routine cranial
      ultrasound examination. RESULTS: We followed 13 infants (three preterm) with
      periventricular cysts. Ten had single or multiple germinolysis cysts and the
      remaining three had choroid plexus cysts. All infants had various kinds of
      underlying complications, including congenital viral infection (two with
      cytomegalovirus and one with rubella),Sotos syndrome (n = 4), intrauterine growth
      retardation (n = 5), large-for-dates(n = 4), congenital heart disease (n =
      1),myelomeningocele (n = 1) and other minor anomalies. All cases of germinolysis
      except for one developed a neurodevelopmental abnormality and/or delay. In
      contrast,all three cases with choroid plexus cysts appeared to develop
      well,despite the underlying complications. CONCLUSIONS: Germinolysis cysts seem
      to be associated with systemic diseases and should be treated as a high-risk sign
      for impaired neurological development.

PMID- 14651544
TI  - Acute hemorrhagic edema of infancy.
AB  - BACKGROUND: Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic
      vasculitis of infants. Even though the cutaneous findings are dramatic in both
      appearance and rapidity of onset, the prognosis is benign. METHODS: We report on
      eight patients with AHEI evaluated from the viewpoints of age, sex, history of
      infection, drug administration or immunization before the onset of skin lesions,
      laboratory findings, cutaneous findings, cutaneous biopsy and treatment. RESULTS:
      The ages of the patients, six of whom were male, ranged between 7 and 27 months.
      Five episodes in our patients occurred in winter. Six patients (75%) had a
      history of recent infection, drug administration or immunization. All patients
      had fever, peripheral edema and large, purpuric, annular or targetoid plaques on
      the face and extremities. Two patients had mucosal involvement (conjunctiva and
      palatum molle). One patient with severe genital involvement had trunk
      involvement. Hematologic and immunologic tests were not diagnostic in any
      patient. Leukocytoclastic vasculitis was demonstrated in four patients for whom a
      cutaneous biopsy was performed. Complete recovery time ranged between 4 and 7
      days. CONCLUSIONS: We believe that AHEI is a benign disorder, despite its
      dramatic appearance. We want to point out that mucosal and trunk involvement may
      also occur in AHEI.

PMID- 14651545
TI  - Acanthosis nigricans is a reliable cutaneous marker of insulin resistance in
      obese Japanese children.
AB  - BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by
      darkening and thickening of skin with formation of irregular folds, usually
      limited to a few specific areas of the body. Recently, AN has been reported to be
      linked to hyperinsulinemia and obesity. The aim of the present study was to
      determine whether or not the presence of AN in obese Japanese children is a
      reliable cutaneous marker. METHODS: The authors analyzed the clinical
      characteristics of 439 obese Japanese children (260 boys, 179 girls; mean age
      10.1 years; mean percentage overweight 51.9%), who had visited Tsuruoka City
      Shonai Hospital in 1990-2000. Eighty-two of the 439 children were examined using
      an oral glucose tolerance test (OGTT). Of these children, the authors
      retrospectively studied 16 subjects: eight with AN and eight without AN (age
      range: 10.8-13.9 years; percentage overweight range: 54.3-97.0%). They were age
      and percentage obesity-matched males with normal glucose tolerance during OGTT.
      Females with normal glucose tolerance during OGTT were excluded from the 16
      subjects because the number was too small and children with impaired glucose
      tolerance or type 2 diabetes during OGTT were also excluded because of glucose
      toxicity. Eighty-two children including the 16 subjects were analyzed at their
      first visit for the presence or absence of AN on the posterior of the neck, and
      for characteristics including age, birthweight, body height, bodyweight,
      percentage overweight, blood pressure, liver function markers serum lipid
      concentrations, fasting plasma glucose concentrations and insulin concentrations
      shown by the results of OGTT. RESULTS: (1) Children with AN showed significantly
      more glucose intolerance including impaired glucose tolerance and type 2 diabetes
      compared with those children without AN, and fasting plasma insulin
      concentrations were most significantly correlated with the presence of AN. (2)
      Insulin resistance based on fasting plasma insulin concentrations was seen in
      significantly more children with AN than in children without AN, even in age and
      percentage obesity-matched subjects with normal glucose tolerance during OGTT.
      CONCLUSIONS: Acanthosis nigricans could be a reliable cutaneous marker of insulin
      resistance in obese Japanese children.

PMID- 14651546
TI  - Adolescent quality of life: a school-based cohort study in Western Australia.
AB  - BACKGROUND: Quality of life (QOL) has received increasing attention in pediatrics
      medicine recently. Improving QOL is the primary justification for many
      interventions, medications and therapies. The present study is a school-based
      longitudinal study which aims to investigate the factors affecting QOL of
      adolescents in Western Australia over a 6-month period. METHODS: A generic self
      reported questionnaire was administered twice to participants from 20 schools in
      Perth at 6 months apart. In addition to QOL scores and physical health status,
      demographic and other information was also collected. For the cohort of 363
      students who participated in the initial survey, 300 of them completed the second
      questionnaire. RESULTS: A significant change in QOL score between baseline and 6
      months was observed. Results from fitting a hierarchical mixed regression model
      indicated that 55% of the variation in QOL was due to differences between
      individuals, and was significantly associated with age, control, opportunities
      and perceptions of physical health, while the remaining variance component could
      be attributed to within-individual changes. Improved control and opportunities
      appeared to have a significant positive impact on QOL, whereas increasing age and
      deterioration in physical health had the opposite effect. CONCLUSIONS: The
      hierarchical regression analysis has enabled valid inferences to be made based on
      the observed longitudinal data. Perceptions of physical health, age, control and
      opportunities available are related to adolescent QOL. The findings have
      implications on evidence-based practices and childhood health issues.

PMID- 14651547
TI  - Physical and mental development of Turkish twins.
AB  - BACKGROUND: Multiple gestations are known to bring some risks in the prenatal and
      natal period, but whether it is a risk for development in childhood is a matter
      of debate. The aim of the present study was to evaluate physical and mental
      development of Turkish twins and then to assess whether being a twin poses risks
      for their development. METHODS: Fifty-two twin pairs (104 children) aged between
      1 and 5 years were enrolled in the study. The control group consisted of 91
      singletons, who were matched according to age, sex, gestational week and maternal
      educational level. The Denver Developmental Screening Test (DDST) was
      administered to assess cognitive development. Student t-test and chi2 test were
      used to compare the two groups. RESULTS: The mean age of the mothers of twins did
      not differ from that of singleton mothers (P > 0.05). Twins were more frequently
      born in cases of assisted fertilization and were more often born via cesarean
      section. The birthweights of twins were lower and they were more frequently
      hospitalized after birth. The breast feeding period was shorter in twins and they
      had more chronic diseases than singletons (P < 0.05). Mothers of twins needed
      more help while caring for their infants. Physical development of twins and
      singletons did not differ statistically (P > 0.05). Twins had more suspect and
      delayed results in the DDST, especially in the language section of the test.
      CONCLUSION: Physical and mental development of twins does not differ
      significantly from singletons except that twins might have a tendency towards
      slow language acquisition.

PMID- 14651548
TI  - Effect of tongue brushing on oral malodor in adolescents.
AB  - BACKGROUND: Halitosis is a common problem in humans, and is a social and
      psychological handicap for those affected by it. Halitosis has a positive
      correlation with the accumulation of bacterial plaque in the oral cavity. AIMS:
      The aim of the present study was to determine the effect of tongue brushing on
      oral malodor in adolescents. METHODS: The subjects of the investigation were 28
      adolescents who had oral malodor and whose average age was 16 +/- 0.12 years.
      Subjects were chosen to participate in the study if they had an established
      routine of oral care, and did not have systemic or periodontal disease or
      dentures (such as fixed prosthesis or partial and total dentures). The subjects
      with oral malodor were randomly assigned into two groups. Individuals in the
      first group received instructions regarding professional procedures of oral care
      from a periodontist. In addition, individuals in this group had the surface of
      their tongue cleaned using a hard toothbrush, wetted with 0.12% chlorhexidine
      gluconate. Individuals in the second group (control) underwent the same
      professional procedures of oral care executed by the same periodontist, however,
      they did not have their tongues cleaned. Oral malodor of individuals was then
      evaluated for all individuals using the organoleptic method. The pH of the
      subjects tongues were recorded before and after treatment. The results of the
      oral malodor test were compared between the two groups. RESULTS: The results of
      the study found that oral malodor scores obtained by an organoleptic method was
      more severe in the second group than the first group, and statistical differences
      were found between the two groups (P < 0.001). CONCLUSION: These results revealed
      that accumulation of bacterial plaque on the tongue is an important factor for
      oral malodor in the adolescents. Oral malodor levels were significantly reduced
      after cleaning the surface of the tongue. Thus, tongue care shouldn't be
      neglected in order to avoid oral malodor.

PMID- 14651549
TI  - Scabies in Thai orphanages.
AB  - BACKGROUND: Scabies outbreaks have emerged in the orphanages in Chiang Mai,
      Thailand. Sulfur has been accepted as the standard treatment for childhood
      scabies in Thailand. Sulfur was administered in the mass treatment in two
      orphanages. The present study surveys the prevalence of scabies in these orphans
      the year following the mass treatment program. METHODS: The authors visited the
      two orphanages over the course of 1 year. Children at the orphanages were
      examined. Cases of scabies and their contacts were treated. RESULTS: The
      prevalence of scabies was 87.3% before the mass treatment, and 2 months after
      treatment the prevalence of scabies was reduced to a prevalence of <10%, which
      was maintained until the end of the present study (P < 0.01 for each visit).
      CONCLUSION: Sulfur is effective for treating scabies outbreaks where the cost of
      treatment is a major concern. In order to control the scabies outbreak and to
      prevent further outbreaks, the authors emphasize that an ongoing process of
      follow up after mass treatment is necessary.

PMID- 14651550
TI  - Novel germline mutation in the RB1 gene with multifocal bone tumors following
      retinoblastoma.

PMID- 14651551
TI  - Opitz trigonocephaly C syndrome associated with hearing loss.

PMID- 14651552
TI  - Serum cytokine concentrations of influenza-associated acute necrotizing
      encephalopathy.

PMID- 14651553
TI  - Rare complication of adrenal neuroblastoma: Budd-Chiari syndrome.

PMID- 14651554
TI  - Pulmonary involvement in a patient with dyskeratosis congenita.

PMID- 14651555
TI  - Dual-chamber pacing in hypertrophic obstructive cardiomyopathy with biventricular
      outflow tract obstruction and severe drug-refractory symptoms in a 9-year-old
      girl.

PMID- 14651556
TI  - Pulmonary veno-occlusive disease associated with partial anomalous pulmonary
      venous connection.

PMID- 14651557
TI  - Use of interferon alpha-2b and prednisolone in the treatment of severe
      intractable diarrhea in a child with systemic mastocytosis.

PMID- 14651558
TI  - Toxic hepatitis due to enalapril in childhood.

PMID- 14651560
TI  - New pediatric guideline for the treatment and management of bronchial asthma in
      Japan.

PMID- 14651559
TI  - Child abuse or Barlow's disease?

PMID- 14651561
TI  - Validation of a self-administered questionnaire in Chinese in the assessment of
      eczema severity.
AB  - The purpose of this study was to validate the Chinese version of the Nottingham
      Eczema Severity Score (NESS) in determining the severity of atopic dermatitis
      (AD). Each parent or patient filled out a questionnaire in Chinese based on the
      NESS. A physician then repeated the NESS independently. Finally, the severity of
      AD was evaluated according to the Scoring Atopic Dermatitis (SCORAD) scale. The
      NESSs, severity grades, and SCORAD were analyzed for agreement and correlation.
      The severity grading agreed with the physician's grading in 38 of 52 parents
      (73%) and in 16 of 18 children (89%) who self-evaluated the severity of their AD.
      The weighted kappa (95% confidence interval [CI]) for parents with children less
      than 10 years old, parents with children > or =10 years old, and patients who
      self-evaluated their AD were 0.79 (0.66-0.91), 0.85 (0.69-1.00), and 0.74 (0.36
      1.00), respectively. The R2 for the NESS by parents, the NESS by patients, and
      the SCORAD scores was 42.1%, 47.5%, and 49.8%, respectively. When compared with
      the parents, the older children who self-evaluated their AD showed a better
      correlation of the NESS with the SCORAD index. The self-administered
      questionnaire appears to be useful in assessing AD severity in Chinese children.

PMID- 14651562
TI  - Epidemiology of skin diseases in school children: a study from northern India.
AB  - Little information is available about the prevalence of skin conditions among
      children in the general population of northern India. Low socioeconomic status,
      malnutrition, overcrowding, and poor standards of hygiene are important factors
      accounting for the distribution of skin diseases in developing countries such as
      India. In order to estimate the burden and relative frequency of dermatologic
      diseases among children in the community, we measured the point prevalence of
      skin conditions in 12,586 Indian school children ages 6-14 years. The overall
      point prevalence of one or more identifiable/apparent skin conditions was 38.8%.
      Of those studied, 3786 children (30%) had only one skin disease, 765 (6%) had
      two, and 336 (2.7%) had three skin pathologies. The most common skin conditions
      and their respective point prevalences were skin infections (11.4%), pityriasis
      alba (8.4%), dermatitis/nonspecific eczemas (5.2%), infestations (5.0%),
      disorders of pigmentation (2.6%), keratinization disorders (mostly keratosis
      pilaris) (1.3%), and nevi/hamartomas (1.1%). This study shows that skin
      conditions are common in children and about one-third of them are affected at any
      given time. The finding that more than 85% of the disorders can be grouped into
      fewer than eight categories is important in designing training programs for
      medical teams involved in the delivery of primary health care services in
      developing countries such as India, where about one-third of the population is
      less than 15 years of age.

PMID- 14651563
TI  - Quality of life in children with pityriasis rosea: a prospective case control
      study.
AB  - Our aim was to investigate the effects on quality of life of pityriasis rosea
      (PR) in children and the concerns of their parents. We recruited all children
      ages 5-16 years with a diagnosis of PR in a primary care setting over a period of
      30 months. Controls were the next child of the same sex and comparable age
      consulting for atopic dermatitis or for conditions unrelated to the skin.
      Information on parental concerns was also gathered. Ten children with PR and 20
      control subjects were recruited. Total Children's Dermatology Life Quality Index
      (CDLQI) scores of children with PR (mean 3.50; 95% confidence interval [CI] 2.66
      4.34) were significantly lower than those of children with atopic dermatitis
      (mean 7.70; 95% CI 5.59-9.81). Children with PR had significantly lower scores
      for symptoms and feelings, personal relationships, and sleep. Total CDLQI scores
      of children with PR were significantly higher than those of children with no
      active skin problem (mean 0.30; 95% CI -0.18 to 0.78). Significantly more parents
      of children with PR had concerns regarding the etiology, infectivity, relapse,
      and complications or dangers of the disease. We concluded that quality of life
      (QOL) of children with PR is significantly less affected than that of children
      with atopic dermatitis and significantly more affected than in children with no
      active skin problem. The major concerns of parents of children with PR are the
      etiology, infectivity, relapse, and complications or dangers. These results have
      important implications on whether active intervention is worthwhile for this
      disease.

PMID- 14651564
TI  - Validation of a Cantonese version of the Children's Dermatology Life Quality
      Index.
AB  - My goal was to assess the validity and reliability of a Cantonese version of the
      Children's Dermatology Life Quality Index (CDLQI). To do so, I invited four
      translators to produce a proper Cantonese translation of the CDLQI. I asked five
      children to complete this version and made adjustments as necessary. I then
      requested 30 children with skin problems and 30 children consulting for problems
      unrelated to the skin in a primary care setting to complete the questionnaire
      before their consultation. A physician assessed the severity of the skin problem
      using a visual analog scale. Some children from both groups completed the
      questionnaire again 7 days later. The CDLQI scores are strongly (gammas = 0.850)
      and significantly (p < 0.01) correlated with physician-rated disease severity.
      The Cantonese CDLQI scores were similar to those of the English version for
      individual skin problems. Correlation of test-retest results is strong (gammas =
      0.958, p < 0.01). Cronbach's alpha is 0.83. I concluded that the Cantonese CDLQI
      is a valid and reliable tool for assessing the effects of skin problems on
      quality of life in children.

PMID- 14651566
TI  - Juvenile chondrodermatitis nodularis helicis: a case report and literature
      review.
AB  - Chondrodermatitis nodularis helicis (CNH) is a disorder that affects adults. Only
      one case of juvenile CNH has been reported, in an 8-year-old child who suffered
      from dermatomyositis. We report another child with juvenile CNH who was not
      afflicted with dermatomyositis or other systemic disorders. The clinical and
      histologic evaluations demonstrated CNH on the helix of the right ear in a 16
      year-old Caucasian girl who was otherwise healthy. Serologic analysis ruled out
      an underlying autoimmune disorder. We conclude that juvenile CNH is extremely
      rare and may occur in patients without dermatomyositis or other systemic
      disorders.

PMID- 14651565
TI  - Epidemiology of pediatric dermatology and allergology in the region of Aargau,
      Switzerland.
AB  - Pediatric dermatology is a new topic and no epidemiologic data exist from
      Switzerland. Therefore we performed a survey of the pediatric population referred
      to the hospital of Aarau, Switzerland, between 1998 and 2001. All inpatients and
      outpatients less than 16 years old with a dermatologic diagnosis were included
      prospectively in our study. Demographic data (age, mean age, sex distribution),
      referral method, pattern and frequency of the different diagnoses in various age
      groups, diagnostic pattern, and therapy were analyzed. A total of 1105 children
      were included, with a slightly higher proportion of girls (53.8% versus 46.2%).
      The average age was 6.8 years and infants and school children represented 60% of
      the study population. Half of the patients (51%) were external referrals, almost
      one-third (29%) presented spontaneously, and the remaining 20% were sent from
      other hospital departments. With a frequency of 25.9%, atopic dermatitis was the
      most frequent diagnosis, followed by pigmented nevi (9.1%) and warts (5.0%).
      Local therapy was prescribed in 66% of patients and systemic therapy in 18.6%.
      Other treatments such as curettage, surgery, cryotherapy, ultraviolet therapy,
      and electrotherapy were rarely performed (2%). We found that atopic dermatitis
      was the most frequent skin disorder seen in all age groups. As this was a
      dermatologic subspecialty clinic, higher frequencies of chronic and uncommon
      dermatoses such as genetic and autoimmune diseases were seen, whereas frequent
      diagnoses such as diaper rash and miliaria were rarely seen and the frequencies
      of other common skin disorders such as scabies, pediculosis, impetigo contagiosa,
      warts, and molluscum contagiosum were expected to be higher compared with the
      figures in the literature. In our study these dermatoses are underreported, as
      most patients are treated by general practitioners and pediatricians. Our survey
      documents the most common skin diseases in childhood primarily seen by
      pediatricians. We emphasize that dermatologic education of medical students,
      primary care physicians, and pediatricians should focus on allergic skin
      diseases, skin infections, pigmentary disorders, and vascular lesions.

PMID- 14651568
TI  - Ecthyma gangrenosum caused by disseminated Exserohilum in a child with leukemia:
      a case report and review of the literature.
AB  - We report an 8-year-old boy with acute leukemia who developed ecthyma gangrenosum
      secondary to infection with Exserohilum spp., a rare cause of human disease. The
      skin, paranasal sinuses and lungs were involved. To the best of our knowledge,
      this is the first report of ecthyma gangrenosum caused by Exserohilum spp. This
      case emphasizes the importance of prompt skin biopsy for early diagnosis and
      treatment of this life-threatening infection.

PMID- 14651567
TI  - Incontinentia pigmenti associated with cerebral palsy and cerebral leukomalacia:
      a case report and literature review.
AB  - Incontinentia pigmenti (IP) is a multisystem disorder with characteristic
      cutaneous signs. After the skin, the central nervous system is the next most
      affected system. We report a child with IP and left-sided hemiparesis and
      cerebral periventricular leukomalacia on magnetic resonance imaging (MRI). The
      MRI findings would support ischemia sustained perinatally.

PMID- 14651569
TI  - Congenital erythropoietic porphyria complicated by squamous cell carcinoma.
AB  - We report two sisters, ages 12 and 8 years, with the characteristic clinical and
      biochemical profile of congenital erythropoietic porphyria (CEP). The disease is
      inherited as an autosomal recessive. The elder sibling had squamous cell
      carcinoma arising from the stump of the amputated left arm with metastases to
      lymph nodes, adrenals, and bone. To our knowledge, this feature has not been
      described in the English language literature, making our patient the first
      documented report of CEP with squamous cell carcinoma.

PMID- 14651570
TI  - Urticarial lesions in a child with acute lymphoblastic leukemia and eosinophilia.
AB  - The hypereosinophilic syndrome (HES) is defined by a longer than 6-month history
      of peripheral blood hypereosinophilia (greater than 1.5 x 10(9)/L), with signs
      and symptoms of internal organ involvement, in the absence of an identifiable
      cause. HES is therefore a diagnosis of exclusion. Patients have been reported who
      initially met the criteria for HES but subsequently developed a rare hematologic
      malignancy known as acute lymphoblastic leukemia with eosinophilia (ALL-Eo). We
      report such a case in a 10-year-old boy who presented to the pediatric
      dermatology clinic with unusual, urticarial skin lesions. Although skin
      involvement is often reported in cases of HES and ALL-Eo, such findings are
      variable and reports in the dermatology literature are few. We emphasize the
      importance of continuous monitoring for underlying malignancy in children with
      urticarial skin lesions in the setting of unexplained hypereosinophilia.

PMID- 14651571
TI  - Childhood pustular psoriasis elicited by the streptococcal antigen: a case report
      and review of the literature.
AB  - The Zumbusch pattern of generalized pustular psoriasis (GPP) classically presents
      as waves of widespread sheets of sterile pustules on brightly erythematous skin.
      The occurrence of this disease in childhood is rare, and fewer than 200 cases
      have been reported in the literature. We describe a 10-year-old boy with GPP who
      had an elevated serum antistreptolysin titer. Several antigenic factors shown to
      elicit GPP have been reported, including withdrawal of steroids, emotional
      stress, and infection. However, we further propose that the group A beta
      hemolytic streptococcus can trigger a flare of GPP. We suggest that if pustular
      psoriasis is suspected clinically, an elevated serum antistreptolysin antibody
      titer may help identify the causative antigen.

PMID- 14651572
TI  - Kawasaki disease with facial nerve paralysis.
AB  - Kawasaki disease (KD) is a multisystem disorder with varying clinical expression.
      We describe an instance of facial nerve paralysis in a patient with KD. A 5-month
      old boy developed fever, irritability, and diarrhea, treated 8 days later with
      cefaclor and ibuprofen. Three days later a confluent, erythematous and papular
      rash appeared, his lips were reddened and swollen, and his white blood count and
      platelet count were 20,900/mm(3) and 558,000/mm(3), respectively. He was admitted
      to the hospital with a diagnosis of KD, and an echocardiogram showed a right
      coronary aneurysm. The patient then developed an acute, right-sided, facial nerve
      peripheral paralysis that resolved over the next 6 weeks. He was treated with
      intravenous immune globulin (IVIG) 2 g/kg and aspirin 100 mg/kg/day with
      improvement of signs and symptoms. This report documents facial nerve paralysis
      as an uncommon complication of KD and points out that it may be a marker of
      increased risk of cardiovascular disease in this disorder.

PMID- 14651573
TI  - Linear porokeratosis associated with disseminated superficial actinic
      porokeratosis: a new example of type II segmental involvement.
AB  - The coexistence of linear porokeratosis (LP) and disseminated superficial actinic
      porokeratosis (DSAP) in a 3-year-old girl with a family history of DSAP is
      presented. Happle proposed loss of heterozygosity (LOH) to explain the origin of
      this unusual phenomenon. Homozygosity would explain why lesions in LP are far
      more pronounced than those of the associated heterozygous DSAP lesions. LOH would
      also explain the early age of presentation of the linear lesions, the family
      history of DSAP, and why LP cases are particularly prone to malignant
      transformation. This case is also important for molecular studies because of the
      presence of heterozygous and homozygous mutated cells in the same patient and the
      familial occurrence of the heterozygous form of the disease.

PMID- 14651574
TI  - Noma-like gangrenous cheilitis in a child with cyclic neutropenia associated with
      myeloperoxidase deficiency.
AB  - An unusual case of cyclic neutropenia and hereditary myeloperoxidase deficiency
      complicated by noma-like gangrenous cheilitis is described. Klebsiella pneumoniae
      and Candida albicans were cultured from the involved area. We present this case
      to increase physician awareness of the possible association of both quantitative
      and qualitative defects of neutrophils and to stress the importance of the early
      and effective management of skin infections that can rapidly progress to severe
      sequelae when associated with profound neutropenia.

PMID- 14651575
TI  - Pneumocystis carinii mimicking neonatal lupus erythematosus-related pneumonitis.
AB  - Neonatal lupus erythematosus (LE) is a rare disease associated with the
      transplacental passage of maternal autoantibodies to infants who manifest
      congenital heart block, skin disease, and less commonly, hematologic and hepatic
      disease. Pulmonary disease is a rare manifestation of neonatal LE and has
      presented as transient pneumonitis. In this report we describe an infant with
      neonatal LE who had the classic skin and hematologic findings of the disease in
      addition to pulmonary disease which might be attributed to neonatal LE-related
      pneumonitis, but in fact was caused by a concomitant Pneumocystis carinii
      infection. This case demonstrates the importance of looking for other causes of
      pulmonary disease in neonatal LE patients.

PMID- 14651576
TI  - Harlequin baby with ecthyma gangrenosum.
AB  - Pseudomonas aeruginosa bacteremia or sepsis often occurs in hospitals, affecting
      mainly children with underlying disease. Ecthyma gangrenosum is classically
      considered a pathognomonic sign of sepsis by P. aeruginosa. The harlequin baby, a
      severe variant of ichthyosis, occurs rarely, and these infants are at high risk
      of cutaneous infections and sepsis. We herein report a harlequin baby who
      developed ecthyma gangrenosum.

PMID- 14651577
TI  - Azathioprine as a treatment for severe atopic eczema in children with a partial
      thiopurine methyl transferase (TPMT) deficiency.
AB  - Azathioprine is a valuable agent in the treatment of severe childhood atopic
      eczema. Thiopurine methyl transferase (TPMT) exhibits autosomal codominant
      polymorphism and plays an important role in the metabolism of azathioprine. In
      most large population groups studied to date, approximately 10% of the population
      had intermediate activity due to heterozygosity at the TPMT locus, and about
      0.33% were TPMT deficient. TPMT deficiency results in the accumulation of
      thioguanine nucleotides and cytotoxic 6-mercaptopurine metabolites. Previously it
      was considered unsafe to treat this group with azathioprine because of what was
      considered to be an unacceptably high risk of toxicity (profound
      myelosuppression). Better understanding of the pharmacogenetics of purine
      metabolism has changed this, and with appropriate dose adjustments, individuals
      who have a partial TPMT deficiency (heterozygotes) can now be treated with
      thiopurines. It seems probable that these individuals are more likely to have a
      therapeutic response while being at lower risk of developing dose-related
      hepatotoxicity because of the reduced doses required to effect a therapeutic
      response. Two patients with severe refractory atopic eczema, both of whom had a
      partial TPMT deficiency, have had an excellent response to treatment with
      azathioprine. They were treated with half-standard doses and response to
      treatment occurred within 2 weeks.

PMID- 14651578
TI  - A disturbing milia eruption.

PMID- 14651579
TI  - What syndrome is this? Cockayne syndrome.

PMID- 14651580
TI  - Halo congenital nevus.

PMID- 14651581
TI  - Unusual course of a halo nevus.

PMID- 14651582
TI  - Re: yellowish papules on flexural areas in a child.

PMID- 14651584
TI  - Multidrug-resistant cutaneous tuberculosis: response to therapy.

PMID- 14651585
TI  - Lymphedema: an additional finding in the charge association.

PMID- 14651587
TI  - Naturally acquired antibody responses to the components of the Plasmodium
      falciparum merozoite surface protein 1 complex.
AB  - Merozoite surface protein 6 (MSP6) and 7 (MSP7) of Plasmodium falciparum are
      peripheral membrane proteins whose cleaved products, MSP636, MSP722 and MSP719,
      are found on the merozoite surface as components of a non-covalently bound
      complex which also contains four polypeptides derived from merozoite surface
      protein 1 (MSP1). We have expressed both the precursor regions and the processed
      mature products of MSP6 and MSP7 in Escherichia coli and showed that these
      recombinant proteins react with human immune sera. In a set of sera collected
      from individuals living in malaria-endemic areas of Southern-central Vietnam,
      antibodies to the mature polypeptides of MSP636 and MSP722 were detected in 50.6
      and 85.6% of the serum samples, whereas antibodies to the precursor regions of
      MSP6 and MSP7 were detected in only 12.1 and 42.5% of the serum samples,
      respectively. The predominant subclass of anti-MSP6 antibodies was IgG1, whereas
      the predominant subclass of anti-MSP7 antibodies was IgG3. In the same set of
      serum samples, the antibody responses to MSP119 are predominantly IgGI, whereas
      antibodies to merozoite surface protein 4 (MSP4) are mainly IgG3. This data is
      consistent with the proposition that, during malaria infection, variable proteins
      induce responses that are predominantly of the IgG3 isotype, and conserved
      proteins induce responses that are predominantly IgG1. The antibodies to MSP6,
      MSP7 and MSP119 all decreased at the time of infection, but increased during the
      convalescent period. No correlation was observed between the antibodies at the
      commencement of the study and absence of parasitaemia during surveillance in this
      population.

PMID- 14651588
TI  - Local skin reaction (chancre) induced following inoculation of metacyclic
      trypanosomes in cattle by tsetse flies is dependent on CD4 T lymphocytes.
AB  - The first visible response in livestock to the bite of a trypanosome-infected
      tsetse fly is the formation of a localized skin reaction, also known as a
      chancre. This is an inflammatory response in the skin associated with swelling
      and an influx of cells. It is thought to be associated with an acquired immune
      response to the injected metacyclic trypanosomes. In this study, we examined the
      role of T lymphocytes in the development of the inflammatory response, by
      depleting cattle of T cell subpopulations and monitoring the development of
      chancres. Depletion of CD4 cells, but not CD8 cells, resulted in a significant
      reduction in chancre formation, confirming that an acquired response mediates the
      inflammatory response. In addition, it was established that the CD4 T cells
      mediate the generation of memory for immunity to a homologueous re-challenge. The
      inflammatory response in the skin did not affect further progress of the
      infection.

PMID- 14651589
TI  - In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface
      antigens associated with severe malaria in African children.
AB  - P. falciparum-infected red blood cells (IRBC) can adhere to endothelial host
      receptors through parasite-encoded, clonally variant surface antigens (VSA). The
      VSA-mediated IRBC adhesion and the acquired VSA-specific antibody response have
      both been linked to IRBC organ tropism and disease severity. Parasites isolated
      from young children with severe malaria (SM) tend to express a limited and
      conserved set of VSA (VSASM) that are both stronger and more commonly recognized
      by IgG in the plasma of malaria-exposed individuals than VSA (VSAUM) expressed by
      parasites causing uncomplicated malaria (UM) in older semi-immune children.
      Establishment of the genetic mechanism underlying changes in VSA expression in
      response to in vitro selective pressure is now possible because of the
      availability of the entire genomic sequence of the P. falciparum clone 3D7. As a
      first step towards direct molecular identification of VSASM-encoding genes in
      3D7, we report here a method of enforcing expression of VSASM-like antigens in
      this parasite clone by a novel selection method using plasma from semi-immune
      children with low VSAUM-specific, but high VSASM-specific, IgG reactivity. In
      addition to the resulting increase in VSA-specific IgG recognition, VSASM
      expressing 3D7(3D7-Dodowa1) showed reduced adhesion to CD36. Finally, levels of
      IgG specific for the VSA expressed by 3D7-Dodowa1 were uniformly higher than
      those of IgG with specificity for VSA expressed by the unselected 3D7 in plasma
      samples from geographically and epidemiologically diverse areas of endemic
      parasite transmission. The described selection method appears a useful tool in
      the identification of genes encoding VSA involved in severe and life-threatening
      P. falciparum malaria.

PMID- 14651590
TI  - A DNA-prime/protein-boost vaccination regimen enhances Th2 immune responses but
      not protection following Schistosoma mansoni infection.
AB  - DNA immunization represents a promising vaccine strategy that has been reasonably
      successful, and will likely play an even greater role in vaccine development as
      these vaccines continue to be improved. We have developed a partially protective
      DNA vaccine against schistosome infection based on a 23-kDa integral membrane
      protein, Sm23. The focus of this study was to compare immunogenicity and efficacy
      of vaccination regimens utilizing Sm23 DNA vaccine alone vs. regimens that
      utilized both Sm23 DNA and Sm23 in recombinant protein form. We found that
      priming and boosting with the Sm23 DNA construct (Sm23-pcDNA) resulted in a
      significant level of protection against challenge infection (36-44%). In
      contrast, altering this protocol by changing the boost from Sm23 DNA to boosting
      with recombinant Sm23 protein (rSm23) formulated in aluminium hydroxide (alum)
      failed to induce a significant reduction in worm burdens. Similarly, mice primed
      and boosted with the rSm23 in alum also did not develop significant levels of
      protection against challenge infection. We hypothesize that the differences in
      the ability to drive protective immunity using the DNA prime-DNA boost strategy
      and the inability to do so when recombinant Sm23 in alum was substituted for Sm23
      DNA is due to driving of different immune responses. In support of this, we found
      that mice primed and boosted with Sm23-pcDNA had Th1-type immune responses
      characterized by low anti-Sm23 IgG1 : IgG2a antibody isotype ratios, whereas mice
      boosted with rSm23 had higher IgG1 : IgG2a ratios. In addition, priming and
      boosting with rSm23 elicited mainly IgG1 antibodies with no detectable IgG2a,
      indicative of a polarized Th2-type immune response. Thus, similar to our earlier
      work, the results of this study show that protective vaccination using Sm23 is
      associated with a Th1 immune response, and efficacy is diminished using protocols
      that diminish this Th1 bias. In our study, this was likely due to the use of the
      Th2-driving adjuvant alum, and future studies are planned where we will compare
      the protective efficacy of rSm23 administered with Th1-type adjuvants.

PMID- 14651591
TI  - Factors influencing Leishmania major infection in IL-4-deficient BALB/c mice.
AB  - The outcome of Leishmania major infection in IL-4-deficient BALB/c mice has been
      a controversial subject. We have shown that IL-4-deficient BALB/c mice infected
      with Leishmania major developed progressive lesions and could not contain the
      replication of the parasites, whereas other studies have reported that IL-4
      deficient mice were able to resist infection. Therefore, we examined different
      factors that can influence the course of Leishmania major infection. We tested
      different lines of IL-4-deficient BALB/c mice and show that the reported
      differences in the outcome of infection were not due to the different genetic
      origin of the embryonic stem cells used to disrupt the IL-4 gene. In addition, we
      infected IL-4-deficient mice with different isolates of L. major parasites and
      show that none of the parasite strains tested were cleared, although some of them
      caused milder pathology. Interestingly, this milder pathology was paralleled by a
      reduced arginase activity of the parasites. We also tested the influence of age
      on the course of Leishmania major infection in IL-4-deficient BALB/c mice and
      show that older mice express a transient resistance. Thus, we conclude that
      differences in the age of the mice and in the arginase activity of the different
      isolates of parasites are factors that can influence the non-healing phenotype of
      IL-4-/- BALB/c mice.

PMID- 14651592
TI  - Humoral immune responses induced by Kudoa sp. (Myxosporea: Multivalvulida) in
      BALB/c mice: oral administration, immunization and cross-reactions with Myxobolus
      aeglefini (Myxosporea: Bivalvulida).
AB  - The majority of Kudoa species infect the somatic muscle of fish, establishing
      cysts. Because there is no effective method to detect infected fish without
      destroying them, these parasitized fish reach the consumer. The elevated humoral
      responses detected previously by us in BALB/c mice immunized with Kudoa sp.
      pseudocyst extracts showed the possible immunopathological effects in man from
      the ingestion of Kudoa-infected fish. In this work, the high IgG1 and IgE levels
      induced by the oral administration of Kudoa pseudocysts to BALB/c mice confirmed
      the allergenic nature of some of their components. An alternative way of
      preparing the soluble extract by using a FastPrep' shaker indicated the
      inconvenience of using sonication to prepare the Kudoa sp. extract. IgG+M, IgG,
      IgG3 and IgA cross-reactions of Kudoa sp. with another myxosporean, Myxobolus
      aeglefini, were found.

PMID- 14651593
TI  - Adrenocortical hormones and interleukin patterns in leprosy.
AB  - The functional status of adrenocortical hormones and their relationship to the
      pattern of inflammatory cytokines in the lepromatous and tuberculoid poles of
      leprosy were investigated. Interleukin (IL)-1beta, IL-6 and tumour necrosis
      factor (TNF)-alpha plasma levels, C-reactive protein (CRP) concentrations and
      erythrocyte sedimentation rates (ESR) were significantly higher in LL/BL
      (lepromatous) leprosy patients than in control subjects. There was a significant
      positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP
      concentrations. IL-1beta was positively correlated with ESR but not with CRP.
      Both baseline and stimulated adrenocorticotropic hormone and cortisol plasma
      levels were not different between patients and control subjects. In contrast,
      adrenal androgen dehydroepiandrosterone sulphate (DHEA-S) plasma levels were
      significantly lower in leprosy patients than in sex-matched control subjects.
      There was a significant inverse correlation between DHEA-S and IL-6, TNF-alpha,
      and CRP concentrations. This finding may be of pathogenetic significance in this
      disease and in other inflammatory states.

PMID- 14651595
TI  - Components of the standard oesophageal manometry.

PMID- 14651594
TI  - In vivo activation of murine peritoneal B1 cells by the filarial nematode
      phosphorylcholine-containing glycoprotein ES-62.
AB  - Mice were subcutaneously implanted with osmotic pumps loaded with ES-62, an
      immunomodulatory phosphorylcholine (PC)-containing glycoprotein secreted by
      filarial nematodes. The concentration of ES-62 was set to give a serum level
      within the range found for PC-containing molecules during natural filarial
      nematode infection of humans. Peritoneal B1 cells were recovered from the mice
      and the effect of exposure to ES-62 on a number of parameters determined ex vivo.
      B1 cells exposed to ES-62 showed an increase in spontaneous proliferation that
      was enhanced by ex vivo exposure to F(ab')(2) fragments of anti-IgM antibodies
      (anti-IgM), to activate via the antigen receptor, or LPS. Consistent with this,
      cell-cycle analysis indicated that cells pre-exposed to ES-62 showed increased
      cell-cycle progression following stimulation with anti-IgM. Pre-exposed cells
      also showed an increase in both spontaneous and anti-IgM induced IL-10 secretion.
      Taken together, these data indicate that ES-62 activates murine B1 cells in vivo.
      Conversely, we have previously shown conventional (B2) B cells to be rendered
      hypo-responsive by in vivo exposure to ES-62 and the different effect on the two
      cell types is discussed in relation to the nature of the antibody response
      arising during filarial nematode infection.

PMID- 14651596
TI  - Interleukin-1 beta selectively increases substance P release and augments the
      ascending phase of the peristaltic reflex.
AB  - Exposure of muscle strips to interleukin (IL)-1beta stimulates substance P (SP)
      expression, suggesting a link between IL-1beta and the increase in SP expression
      during intestinal inflammation. The present study examined whether the SP
      expression induced by IL-1beta is reflected by enhanced SP release and SP
      mediated reflex activity. Exposure of innervated longitudinal colonic muscle
      strips to IL-1beta for 8 h increased SP synthesis in, and greater SP release from
      excitatory motor neurones in response to KCl or electrical field stimulation
      (EFS), and enhanced longitudinal muscle contraction in response to EFS. IL-1 Ra
      and IL-1beta antibody blocked IL-1beta-induced increase in SP release and muscle
      contraction. Neither vasoactive intestinal peptide (VIP) nor somatostatin release
      was increased. The increase in SP release was reflected in enhanced circular
      muscle contraction in response to stretch. VIP-mediated descending relaxation of
      circular muscle was not affected. The selective increase in ascending contraction
      induced by exposure to IL-1beta was blocked by IL-1 Ra or IL-1beta antibody. We
      conclude that the selective increase in SP expression induced by IL-1beta in
      excitatory motor neurones is reflected by enhanced SP release and longitudinal
      muscle contraction in response to EFS, and enhanced SP release and circular
      muscle contraction during the ascending phase of the peristaltic reflex.

PMID- 14651597
TI  - The effect of sildenafil on oesophageal motor function in healthy subjects and
      patients with nutcracker oesophagus.
AB  - Type 5 phosphodiesterase terminates the action of nitric oxide (NO) induced 3',5'
      cyclic monophosphate (cGMP). Sildenafil inhibits this phosphodiesterase,
      increases cellular cGMP concentrations and enhances NO-induced smooth muscle
      relaxation. We investigated the effect of sildenafil on the oesophageal motor
      function of healthy subjects and patients with nutcracker oesophagus. Eight
      healthy volunteers and nine patients with nutcracker oesophagus participated in
      this study. The participants underwent oesophageal manometries on two separate
      days after either 20 mL of distilled water or 0.8 mg kg-1 sildenafil dissolved in
      20 mL of water was infused into the stomach. Lower oesophageal sphincter (LOS)
      resting pressure, the duration of LOS relaxation and the amplitudes of
      oesophageal pressure waves were examined before, and 7.5, 15, 30 and 60 min after
      either placebo or sildenafil. In both healthy subjects and patients with
      nutcracker oesophagus, sildenafil decreased resting LOS pressure and the
      amplitude of peristaltic pressure waves at 3, 8 and 13 cm above LOS. Sildenafil
      also prolonged the duration of LOS relaxation. It had no effect on the velocity
      of peristalsis or the amplitude of peristaltic pressure waves 18 cm above LOS.
      Sildenafil may be considered as an alternative treatment in nutcracker oesophagus
      although there are several limitations to be overcome.

PMID- 14651598
TI  - Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions.
AB  - The cyclic nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine
      3',5'-cyclic monophosphate (cGMP) mediate the inhibitory effects of vasoactive
      intestinal polypeptide and nitric oxide on oesophageal smooth muscle.
      Phosphodiesterases (PDE) terminate their actions. We hypothesized that PDE
      inhibitors alter nerve-induced responses of oesophageal and lower oesophageal
      sphincter (LES) smooth muscle. An electrical field known to activate intrinsic
      oesophageal nerves was used to stimulate transverse muscle strips from the
      opossum oesophagus. This produced a contractile off-response from circular
      oesophageal muscle and a biphasic relaxation of the LES - an initial rapid
      relaxation (R1) and a slower sustained relaxation (R2). The effects on LES and
      oesophageal muscle of zaprinast (type V), zardaverine (type III/IV) and
      theophylline (non-specific) PDE inhibitors were explored. All three PDE
      inhibitors decreased LES tone and attenuated the off-response. Zaprinast and
      theophylline increased the latency of the off-response. Zaprinast prolonged R1,
      and slowed its recovery. It also increased the percentage relaxation of the
      second R2. Zardaverine increased the percentage relaxation of R2. Theophylline
      slowed the recovery of R2. PDEs play a role in maintaining LES tone and its
      recovery after LES relaxation. They may also modulate oesophageal motor activity.

PMID- 14651599
TI  - Coupling and innervation patterns of interstitial cells of Cajal in the deep
      muscular plexus of the guinea-pig.
AB  - Interstitial cells in the deep muscular plexus (ICC-DMP) are thought to be
      essential for neurotransmission in the circular muscle. There is evidence for gap
      junctions within the ICC-DMP network and between ICC-DMP and muscle cells;
      however, there is no evidence for functional coupling via these gap junctions. In
      addition, the innervation of individual ICC-DMP has not been studied. We
      investigated these questions by injecting the dye Lucifer yellow into ICC-DMP of
      guinea-pig ileum. Nerves were labelled immunohistochemically for protein gene
      product 9.5. Cells were imaged by confocal microscopy. Most (79%) of the dye
      injected ICC-DMP were coupled to one to five other ICC-DMP, and 86% of them were
      coupled to one to five circular muscle cells. Octanol effectively blocked all
      coupling. Incubation in pH 6.8-7.0 reduced ICC-ICC coupling to 49% and ICC-muscle
      coupling to 32%. In contrast, pH 7.8-7.9 increased ICC-ICC and ICC-muscle
      coupling to 100%. Most ICC somata (95%) and processes (60%) were in close
      proximity with both nerve fibres and smooth muscle cells. These results provide
      direct evidence for functional coupling within the ICC-DMP network, and between
      this network and cells of the outer circular muscle layer and showed that
      coupling can be affected by pH.

PMID- 14651600
TI  - Kit/stem cell factor receptor-induced phosphatidylinositol 3'-kinase signalling
      is not required for normal development and function of interstitial cells of
      Cajal in mouse gastrointestinal tract.
AB  - Signalling mediated by the receptor tyrosine kinase c-Kit is required for normal
      development of interstitial cells of Cajal (ICC). c-Kit activates several
      signalling pathways, including the phosphatidylinositol 3'-kinase (PI3'-kinase)
      pathway. The signals required for ICC development and maintenance are not well
      understood. Studies indicate a role for PI3'-kinase. We studied ICC function and
      morphology in mice homozygous for the tyrosine 719 to phenylalanine c-Kit
      mutation, which disrupts all PI3'-kinase binding to c-Kit. Functionally, the
      electrical slow waves in the jejunum and inhibitory junction potentials were
      normal in adult mutants. Morphologically, the distribution of ICC was not altered
      in mutants. There was no difference in the density of ICC in the jejunum of
      adults or newborns from quantitative analysis of c-Kit immunoreactivity. The
      number of ICC obtained in culture was the same using mutants or wild-type
      littermates. The density and organization of nerves in the jejunum of mutants was
      not affected. Deletion of c-Kit-induced PI3'-kinase signalling does not affect
      the function or development of ICC in the mouse. This is an important and
      counterintuitive result, given the role of PI3'-kinase signalling downstream of c
      Kit and the role of both c-Kit and PI3'-kinase individually in ICC development.

PMID- 14651601
TI  - Neurochemical coding of myenteric neurones in the human gastric fundus.
AB  - The major functions of the stomach are under the control of the enteric nervous
      system (ENS), but the neuronal circuits involved in this control are largely
      unknown in humans. Enteric neurones can be characterized by their neuromediator
      or marker content, i.e. by neurochemical coding. The purpose of this study was to
      characterize the presence and co-localization of neurotransmitters in myenteric
      neurones of the human gastric fundus. Choline acetyltransferase (ChAT), neurone
      specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide
      synthase (NOS), substance P (SP) were detected by immunohistochemical methods in
      whole mounts of gastric fundus myenteric plexus (seven patients). Antibodies
      against ChAT and NOS labelled the majority of myenteric neurones identified by
      NSE (57.2 +/- 5.6% and 40.8 +/- 4.5%, respectively; mean +/- SD). The proportions
      of VIP- and SP-immunoreactive neurones were significantly smaller, constituting
      19.6 +/- 6.9% and 16.0 +/- 3.7%, respectively. Co-localization studies revealed
      five major populations representing over 75% of the myenteric neurones: ChAT/-,
      30.1 +/- 6.1%; NOS/-, 24.2 +/- 4.4%; ChAT/SP/-, 8.3 +/- 3.1%; NOS/VIP/-, 7.2 +/-
      6.0%; ChAT/VIP/-, 4.9 +/- 2.6. Some similarities are apparent in the
      neurochemical coding of myenteric neurones in the stomach and intestine of
      humans, and between the stomach of humans and animals, but striking differences
      exist. The precise functional role of the neurochemically identified classes of
      neurones remains to be determined.

PMID- 14651602
TI  - Is there a role for the IHH gene in Hirschsprung's disease?
AB  - Hirschsprung disease (HSCR) is characterized by the absence of ganglion cells
      along a variable length of the intestine. HSCR has a complex genetic aetiology
      with 50% of the patients unexplained by mutations in the major HSCR genes. The
      Ihh gene is involved in the development of the enteric nervous system (ENS) and
      Ihh mutant mice present with a phenotype reminiscent of HSCR. The requirement of
      Ihh signalling for the proper development of the ENS, together with the evidence
      presented by the Ihh murine model, prompted us to investigate the involvement of
      the human IHH gene in HSCR. Sequence analysis revealed seven single nucleotide
      polymorphisms, six of which were new. Allele and haplotype frequencies were
      compared between cases and controls, and, among the cases, between genders,
      between different phenotypes, and between patients with different mutation status
      in the main HSCR genes. Despite the involvement of IHH in the development of the
      ENS, IHH is not a major gene in HSCR. Nevertheless, as the manifestation of the
      HSCR phenotype is genetic background dependent, polymorphic loci should be tested
      simultaneously to characterize gene-gene interaction. The involvement of IHH in
      other intestinal anomalies should be investigated.

PMID- 14651603
TI  - Cholinergic transmission to colonic circular muscle of children with slow-transit
      constipation is unimpaired, but transmission via NK2 receptors is lacking.
AB  - Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones
      supplying human colonic circular muscle (CCM). Some children with slow-transit
      constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM
      suggesting a deficit in neuromuscular transmission. This study aimed to test this
      possibility. Seromuscular biopsies of transverse colon were obtained
      laparoscopically from STC children (37, 17 with low density of TK
      immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were
      obtained from adults undergoing colonic resection for cancer. CCM contractions
      were measured isotonically and responses to carbachol, neurokinin A (NKA) and
      electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked
      contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly
      depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR
      48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult
      transverse CCM, but had no effect on STC preparations. Thus, neuromuscular
      transmission in both adults and STC children is predominantly cholinergic and
      this component is unimpaired in the latter, indicating that reduced TK
      immunoreactivity is not a marker for depressed cholinergic responses. Although
      pharmacologically responsive TK receptors are present in STC colon, we did not
      detect neuromuscular transmission mediated by release of TKs in these
      preparations.

PMID- 14651604
TI  - Influence of sex and experimental protocol on the effect of maternal deprivation
      on rectal sensitivity to distension in the adult rat.
AB  - Neonatal maternal separation induces visceral hyperalgesia before and after
      stress in male rats. This study compares the effects on sensitivity to rectal
      distension in adult male and female rats, using two protocols of deprivation.
      Between postnatal days 1 and 14, maternal deprivation was performed for 2 h per
      day according to a protocol of type M (removal of all pups from home cage) or
      type P (separation of half of littermates). Visceral sensitivity was assessed at
      12 weeks of age by the number of abdominal contractions induced by rectal
      distension before and after restraint stress. Calcitonin gene-related peptide
      (CGRP) was identified in the rectal wall by immunohistochemistry. In basal
      conditions, both separation protocols induced hyperalgesia, that was greater
      after type M than type P, and in females than in males for type P separation.
      Acute restraint stress induced hyperalgesia in control females only, and this
      effect was similarly enhanced by both type P and M separation. No difference was
      found between controls and deprived rats in rectal CGRP immunoreactivity which
      was greater in females and increased after rectal distension. These results
      indicate that long-term visceral hyperalgesia depends upon the type of maternal
      deprivation and that females are more sensitive than males.

PMID- 14651605
TI  - The effect of new diagnostic criteria for irritable bowel syndrome on community
      prevalence estimates.
AB  - The 'Rome' criteria for irritable bowel syndrome (IBS) have evolved over 15 years
      with four published versions. The impact of these changes on community prevalence
      rates is not known. Study aims were to estimate the prevalence of IBS using the
      four Rome criteria and agreement between Rome II and previous criteria.
      Questionnaires were mailed to a random sample of Olmsted County, Minnesota
      residents in 1992. Age- and gender-adjusted prevalence estimates were calculated
      for Rome II (1999), Rome I (1992), Rome (1990), and Rome (1989) criteria. Per
      cent agreement and kappa values were calculated to assess agreement. Of 892
      eligible subjects, 643 (72%) responded. The age- and gender-adjusted prevalence
      of IBS was 5.1% [95% confidence interval (CI): 3.1, 7.0], 6.8% (95% CI: 4.7,
      8.9), 5.1% (95% CI: 3.2, 7.1) and 27.6% (95% CI: 23.6, 31.5), respectively. In
      comparison with Rome II criteria, per cent agreement and kappa values were 97.2%
      and 0.78 (95% CI: 0.69, 0.88), 96.4% and 0.68 (95% CI: 0.55, 0.80), and 79.0% and
      0.29 (95% CI: 0.19, 0.40), respectively. Thus, although differences were seen
      with the older criteria, compared with the Rome I criteria, good agreement was
      seen and community prevalence estimates were similar with the Rome II criteria.

PMID- 14651606
TI  - Restricting restriction.
AB  - Systems biology is a new, fashionable and well-funded discipline, which to quote
      from a recent review aims to 'examine the structure and dynamics of cellular and
      organismal function, rather than the characteristics of isolated parts of a cell
      or organism em leader ' (Kitano, H. (2002) Science 295:1662-1664). Systems
      biology will do this by profiting from the vast amounts of biological information
      that are available in the genomics era and make extensive use of computer
      modelling. But: 'many breakthroughs in experimental devices, advanced software
      and analytical methods are required before the achievements of system biology can
      live up to their much-touted potential'. This edition of Molecular Microbiology
      contains a paper that is the product of traditional experimental biology but
      which could serve as a test case for systems biology. The paper shows how
      bacteria integrate such disparate subsystems as DNA restriction, homologous
      recombination and regulated proteolysis to protect their chromosomes from
      degradation. When systems biology can predict this level of choreography, it will
      be a mature discipline.

PMID- 14651607
TI  - Regulatory proteins with a sense of direction: cell cycle signalling network in
      Caulobacter.
AB  - Localization of kinases and other signalling molecules at discrete cellular
      locations is often an essential component of signal transduction in eukaryotes.
      Caulobacter crescentus is a small, single-celled bacterium that presumably lacks
      intracellular organelles. Yet in Caulobacter, the subcellular distribution of
      several two-component signal transduction proteins involved in the control of
      polar morphogenesis and cell cycle progression changes from a fairly dispersed
      distribution to a tight accumulation at one or both poles in a spatial and
      temporal pattern that is reproduced during each cell cycle. This cell cycle
      dependent choreography suggests that similarly to what happens in eukaryotes,
      protein localization provides a means of modulating signal transduction in
      bacteria. Recent studies have provided important insights into the biological
      role and the mechanisms for the differential localization of these bacterial
      signalling proteins during the Caulobacter cell cycle.

PMID- 14651608
TI  - Global regulation of virulence and the stress response by CsrA in the highly
      adapted human gastric pathogen Helicobacter pylori.
AB  - Although successful and persistent colonization of the gastric mucosa depends on
      the ability to respond to changing environmental conditions and co-ordinate the
      expression of virulence factors during the course of infection, Helicobacter
      pylori possesses relatively few transcriptional regulators. We therefore
      investigated the contribution of the regulatory protein CsrA to global gene
      regulation in this important human pathogen. CsrA was necessary for full motility
      and survival of H. pylori under conditions of oxidative stress. Loss of csrA
      expression deregulated the oxidant-induced transcriptional responses of napA and
      ahpC, the acid induction of napA, cagA, vacA, the urease operon, and fur, as well
      as the heat shock responses of napA, groESL and hspR. Although the level of napA
      transcript was higher in the csrA mutant, its stability was similar in the wild
      type and mutant strains, and less NapA protein was produced in the mutant strain.
      Finally, H. pylori strains deficient in the production of CsrA were significantly
      attenuated for virulence in a mouse model of infection. This work provides
      evidence that CsrA has a broad role in regulating the physiology of H. pylori in
      response to environmental stimuli, and may be important in facilitating
      adaptation to the different environments encountered during colonization of the
      gastric mucosa. Furthermore, CsrA appears to mediate its effects in H. pylori at
      the post-transcriptional level by influencing the processing and translation of
      target transcripts, with minimal effect on the stability of the target mRNAs.

PMID- 14651609
TI  - Characterization of a non-mitochondrial type I phosphatidylserine decarboxylase
      in Plasmodium falciparum.
AB  - In search of key enzymes in Plasmodium phospholipid metabolism, we demonstrate
      the presence of a parasite-encoded phosphatidylserine decarboxylase (PSD) in the
      membrane fraction of Plasmodium falciparum-infected erythrocytes. PSD cDNA,
      encoding phosphatidylserine decarboxylase (PfPSD), was cloned by screening a
      directional cDNA library derived from the trophozoite erythrocytic stage. The
      corresponding PfPSD gene is located on chromosome 9 of P. falciparum, contains
      one intron of 938 nucleotides and is transcribed into a 3.7 kb mRNA. PfPSD cDNA
      encodes a putative protein of 362 amino acids, with a predicted molecular mass of
      42.6 kDa, which clearly belongs to the type I PSD family. Only a 35 kDa
      polypeptide was detected in the parasite using a specific rabbit antiserum. PfPSD
      has a 314VGSS317 sequence near its carboxyl-terminus that is related to the
      Escherichia coli, yeast and human LGST motif, which is the site of proenzyme
      processing. PSD enzyme was expressed in E. coli with a KM of 63 +/- 19 microM and
      a VMAX of 680 +/- 49 nmol of phosphatidylethanolamine formed h-1 mg-1 protein.
      Site-directed mutagenesis of the VGSS active site demonstrated that the PfPSD
      proenzyme was processed into two non-identical subunits (alpha and beta) and
      revealed the crucial role played by each residue in enzyme processing and
      activity. Using indirect immunofluorescence, PfPSD labelling was co-localized
      with an endoplasmic reticulum marker, but not with a mitochondrial vital dye.
      This P. falciparum PSD is the first type I PSD identified in the endoplasmic
      reticulum compartment.

PMID- 14651610
TI  - The antioxidant systems in Toxoplasma gondii and the role of cytosolic catalase
      in defence against oxidative injury.
AB  - Superoxide dismutase, catalase, glutathione peroxidase and peroxiredoxins form an
      antioxidant network protecting cells against reactive oxygen species (ROS).
      Catalase is a potent H2O2-detoxifying enzyme, which is unexpectedly absent in
      some members of the Kinetoplastida and Apicomplexa, but present in Toxoplasma
      gondii. In T. gondii, catalase appears to be cytosolic. In addition, T. gondii
      also possesses genes coding for other types of peroxidases, including
      glutathione/thioredoxin-like peroxidases and peroxiredoxins. This study presents
      a detailed analysis of the role of catalase in the parasite and reports the
      existence of antioxidant enzymes localized in the cytosol and the mitochondrion
      of T. gondii. The catalase gene was disrupted and, in addition, T. gondii cell
      lines overexpressing either catalase or a cytosolic 1-cys peroxiredoxin, TgPrx2,
      under the control of a strong promoter were created. Analysis of these mutants
      confirmed that the catalase activity is cytosolic and is encoded by a unique gene
      in T. gondii. Furthermore, the catalase confers protection against H2O2 exposure
      and contributes to virulence in mice. The overexpression of Prx2 also increases
      protection against H2O2 treatment, suggesting that catalase and other peroxidases
      function as a defence mechanism against endogenously produced reactive oxygen
      intermediates and the oxidative stress imposed by the host.

PMID- 14651611
TI  - Macroautophagy is dispensable for intracellular replication of Legionella
      pneumophila in Dictyostelium discoideum.
AB  - The Gram-negative bacterium Legionella pneumophila is a facultative intracellular
      pathogen of free-living amoebae and mammalian phagocytes. L. pneumophila is
      engulfed in phagosomes that initially avoid fusion with lysosomes. The phagosome
      associates with endoplasmic reticulum (ER) and mitochondria and eventually
      resembles ER. The morphological similarity of the replication vacuole to
      autophagosomes, and enhanced bacterial replication in response to macroautophagy
      inducing starvation, led to the hypothesis that L. pneumophila infection requires
      macroautophagy. As L. pneumophila replicates in Dictyostelium discoideum, and
      macroautophagy genes have been identified and mutated in D. discoideum, we have
      taken a genetic and cell biological approach to evaluate the relationship between
      host macroautophagy and intracellular replication of L. pneumophila. Mutation of
      the apg1, apg5, apg6, apg7 and apg8 genes produced typical macroautophagy
      defects, including reduced bulk protein degradation and cell viability during
      starvation. We show that L. pneumophila replicates normally in D. discoideum
      macroautophagy mutants and produces replication vacuoles that are morphologically
      indistinguishable from those in wild-type D. discoideum. Furthermore, a green
      fluorescent protein (GFP)-tagged marker of autophagosomes, Apg8, does not
      systematically co-localize with DsRed-labelled L. pneumophila. We conclude that
      macroautophagy is dispensable for L. pneumophila intracellular replication in D.
      discoideum.

PMID- 14651612
TI  - Self-association of EPEC intimin mediated by the beta-barrel-containing anchor
      domain: a role in clustering of the Tir receptor.
AB  - Outer membrane intimin directs attachment of enteropathogenic Escherichia coli
      (EPEC) via its Tir receptor in mammalian target cell membranes. Phosphorylation
      of Tir triggers local actin polymerization and the formation of 'pedestal-like'
      pseudopods. We demonstrate that the intimin protein contains three domains, a
      flexible N-terminus (residues 40-188), a central membrane-integrated beta-barrel
      (189-549), and a tightly folded Tir-binding domain (550-939). Intimin was shown
      by electron microscopy to form ring-like structures with an approximately 7 nm
      external diameter and an electron dense core, and to form channels of
      50picoSiemens conductance in planar lipid bilayers. Gel filtration, multiangle
      light scattering and cross-linking showed that this central beta-barrel membrane
      anchoring domain directs intimin dimerization. Isothermal titration calorimetry
      revealed a high affinity, single-binding site interaction of 2 : 1 stoichiometry
      between dimeric intimin and Tir, and modelling suggests that this interaction
      determines a reticular array-like superstructure underlying receptor clustering.
      In support of this model, actin rearrangement induced in Tir-primed cultured
      cells by intimin-containing proteoliposomes was dependent on the concentration of
      both intimin and Tir, and co-localized with clustered phosphorylated Tir.

PMID- 14651613
TI  - Recognition of individual genes in a single bacterial cell by fluorescence in
      situ hybridization--RING-FISH.
AB  - Fluorescence in situ hybridization (FISH) using rRNA targeted oligonucleotide
      probes is a standard method for identification of microorganisms in environmental
      samples. Apart from its value as a phylogenetic marker ribosomal RNA has always
      been the favoured target molecule for FISH because of its abundance in all cells,
      whereas plasmids and DNA were regarded as unsuitable targets because of their low
      copy number. Here we present an improved FISH technique, which is based on
      polynucleotide probes. It goes beyond the detection of high copy intracellular
      nucleic acids such as rRNA (up to 10(4)-10(5) copies per cell) and allows for the
      first time the in situ detection of individual genes or gene fragments on
      plasmids (10(1)-10(3) copies per cell) and chromosomal DNA (<10 copies per cell)
      in a single cell. Using E. coli as model organism we were able to detect in situ
      cells harbouring the antibiotic resistance gene beta lactamase on high, medium
      and low copy plasmids as well as the chromosomal encoded housekeeping gene
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Furthermore, we detected the
      prepilin peptidase gene xpsO in the plant pathogen Xanthomonas campestris in
      situ. Because of the characteristic hybridization signal obtained with this
      method--a halo-like, ring-shaped concentration of fluorescence in the cell
      periphery--we coined the term RING-FISH (recognition of individual genes) to
      differentiate it from conventional FISH.

PMID- 14651614
TI  - Characterization of two Pseudomonas putida lipopeptide biosurfactants, putisolvin
      I and II, which inhibit biofilm formation and break down existing biofilms.
AB  - Pseudomonas putida strain PCL1445 was isolated from roots of plants, grown on a
      site polluted with polycyclic aromatic hydrocarbons. PCL1445 produces
      biosurfactant activity at the end of the exponential growth phase. High
      performance liquid chromatography (HPLC) analysis of supernatant extracts of
      PCL1445 showed two peaks with surface-tension reducing activity, tentatively
      assigned as biosurfactants putisolvin I and putisolvin II and was followed by
      structural analyses. A transposon mutant of PCL1445, strain PCL1436, which lacks
      the two surface-active peaks appeared to be mutated in an open reading frame
      (ORF) with amino acid homology to various lipopeptide synthetases. Structural
      analyses of the two biosurfactants of PCL1445 revealed that both are novel cyclic
      lipodepsipeptides with a hexanoic lipid chain connected to the N-terminus of a 12
      amino-acid peptide moiety, in which the C-terminal carboxylic acid group forms an
      ester with the hydroxyl side-chain of Ser9. The difference between the two
      structures is located in the second amino acid from the C-terminus, being valine
      for putisolvin I, and leucine/isoleucine for putisolvin II. We show that these
      novel compounds lower the surface tension and influence the biofilm development
      on polyvinyl chloride (PVC). Biofilm formation of the bio-synthetic mutant
      PCL1436 was strongly increased containing more cells, which formed aggregates
      earlier as compared with wild-type PCL1445 biofilms. Using purified putisolvin I
      and II it was shown that biofilm formation of different Pseudomonas strains was
      inhibited and most interestingly, that both putisolvins are also able to break
      down existing Pseudomonas biofilms.

PMID- 14651615
TI  - Targeted gene replacement of a ferredoxin gene in Trichomonas vaginalis does not
      lead to metronidazole resistance.
AB  - Ferredoxin, Fd, is often deficient in metronidazole-resistant strains of
      Trichomonas vaginalis and is thought to be necessary for drug activation. To
      directly test whether Fd is essential for metronidazole susceptibility, gene
      replacement technology has been developed for T. vaginalis. The selectable marker
      gene neomycin phosphotransferase (NEO) flanked by approximately 2.6 and
      approximately 2.0 kBp of the Fd 5' and 3' flanking regions (pKO-FD-NEO) was
      introduced into cells on linear DNA and selected for NEO gene expression. Stable
      transformants were shown to contain the NEO gene in the Fd locus and to have
      completely lost the Fd gene. Northern and immunoblot analyses confirm the loss of
      Fd mRNA and protein in pKO-FD-NEO cells. Analyses of the activity of
      hydrogenosomal proteins in Fd KO cells show a fourfold increase in hydrogenase
      activity and a 95% decrease in pyruvate/ferredoxin oxidoreductase (PFO) activity.
      In contrast, PFO and hydrogenase mRNA levels are unchanged. Surprisingly, Fd KO
      cells are not resistant to metronidazole under aerobic or anaerobic conditions.
      These cells are capable of producing molecular hydrogen, albeit at 50% the level
      of the parental strain, demonstrating that the Fd gene product eliminated in KO
      cells is neither necessary for hydrogen production nor metronidazole activation.
      Together these data indicate the presence of unidentified Fds or flavodoxins
      capable of drug activation or an unidentified mechanism that does not require
      either PFO or Fd for metronidazole activation.

PMID- 14651616
TI  - Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent
      proteolytic degradation of multiple virulence factors by SpeB.
AB  - A globally disseminated strain of M1T1 group A Streptococcus (GAS) has been
      associated with severe infections in humans including necrotizing fasciitis and
      toxic shock syndrome. Recent clinicoepidemiologic data showed a striking inverse
      relationship between disease severity and the degree to which M1T1 GAS express
      the streptococcal cysteine protease, SpeB. Electrophoretic 2-D gel analysis of
      the secreted M1T1 proteome, coupled with MALDI-TOF mass spectroscopy, revealed
      that expression of active SpeB caused the degradation of the vast majority of
      secreted GAS proteins, including several known virulence factors. Injection of a
      SpeB+/SpeA- M1T1 GAS strain into a murine subcutanous chamber model of infection
      selected for a stable phase-shift to a SpeB-/SpeA+ phenotype that expressed a
      full repertoire of secreted proteins and possessed enhanced lymphocyte
      stimulating capacity. The proteome of the SpeB-in vivo phase-shift form closely
      matched the proteome of an isogenic speB gene deletion mutant of the original
      M1T1 isolate. The absence or the inactivation of SpeB allowed proteomic
      identification of proteins in this M1T1 clone that are not present in the
      previously sequenced M1 genome including SpeA and another bacteriophage-encoded
      novel streptodornase allele. Further proteomic analysis of the M1T1 SpeB+ and
      SpeB- phase-shift forms in the presence of a cysteine protease inhibitor
      demonstrated differences in the expression of several proteins, including the in
      vivo upregulation of SpeA, which occurred independently of SpeB inactivation.

PMID- 14651617
TI  - Is modification sufficient to protect a bacterial chromosome from a resident
      restriction endonuclease?
AB  - It has been generally accepted that DNA modification protects the chromosome of a
      bacterium encoding a restriction and modification system. But, when target
      sequences within the chromosome of one such bacterium (Escherichia coli K-12) are
      unmodified, the cell does not destroy its own DNA; instead, ClpXP inactivates the
      nuclease, and restriction is said to be alleviated. Thus, the resident chromosome
      is recognized as 'self' rather than 'foreign' even in the absence of
      modification. We now provide evidence that restriction alleviation may be a
      characteristic of Type I restriction-modification systems, and that it can be
      achieved by different mechanisms. Our experiments support disassembly of active
      endonuclease complexes as a potential mechanism. We identify amino acid
      substitutions in a restriction endonuclease, which impair restriction alleviation
      in response to treatment with a mutagen, and demonstrate that restriction
      alleviation serves to protect the chromosome even in the absence of mutagenic
      treatment. In the absence of efficient restriction alleviation, a Type I
      restriction enzyme cleaves host DNA and, under these conditions, homologous
      recombination maintains the integrity of the bacterial chromosome.

PMID- 14651618
TI  - Aberrant cardiolipin metabolism in the yeast taz1 mutant: a model for Barth
      syndrome.
AB  - In eukaryotic cells, the acyl species of the phospholipid cardiolipin (CL) are
      more highly unsaturated than those of the other membrane phospholipids. Defective
      acylation of CL with unsaturated fatty acids and decreased total CL are
      associated with Barth syndrome, an X-linked cardio- and skeletal myopathy
      attributed to a defect in the gene G4.5 (also known as tafazzin). We constructed
      a yeast mutant (taz1) containing a null mutation in the homologue of the human
      G4.5 gene. The yeast taz1Delta mutant was temperature sensitive for growth in
      ethanol as sole carbon source, but grew normally on glucose or glycerol plus
      ethanol. Total CL content was reduced in the taz1Delta mutant, and monolyso-CL
      accumulated. The predominant CL acyl species found in wild-type cells, C18:1 and
      C16:1, were markedly reduced in the mutant, whereas CL molecules containing
      saturated fatty acids were present. Interestingly, CL synthesis increased in the
      mutant, whereas expression of the CL structural genes CRD1 and PGS1 did not,
      suggesting that de novo biosynthetic enzyme activities are regulated by CL
      acylation. These results indicate that the taz1Delta mutant is an excellent
      genetic tool for the study of CL remodelling and may serve as a model system for
      the study of Barth syndrome.

PMID- 14651619
TI  - Characterization of components of the mismatch repair machinery in Trypanosoma
      brucei.
AB  - Mismatch repair is one of a number of DNA repair pathways that cells possess to
      deal with damage to their genome. Mismatch repair is concerned with the
      recognition and correction of incorrectly paired bases, which can be base-base
      mismatches or insertions or deletions of a few bases, and appears to have been
      conserved throughout evolution. Primarily, this is concerned with increasing the
      fidelity of DNA replication, but also has important roles in the regulation of
      homologous recombination and the correction of chemical damage. In this study, we
      describe five genes in the protistan parasite Trypanosoma brucei that are likely
      to be involved in nuclear mismatch repair. The predicted T. brucei mismatch
      repair genes are diverged compared with their likely counterparts in the other
      eukaryotes examined to date. To demonstrate that these do indeed encode a
      functional nuclear mismatch repair system, we made T. brucei null mutants in two
      of the genes, MSH2 and MLH1, that are likely to be central to the functioning of
      the mismatch repair machinery. These mutations resulted in increased rates of
      sequence variation at a number of microsatellite loci in the parasite genome, and
      led to increased tolerance to the alkylating agent N-methyl-N'-nitro-N
      nitrosoguanidine, both phenotypes consistent with mismatch repair impairment.

PMID- 14651620
TI  - EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in
      mycobacteria, octamerizes cooperatively on its operator.
AB  - Ethionamide (ETH) is an important second-line antitubercular drug used for the
      treatment of patients infected with multidrug-resistant Mycobacterium
      tuberculosis. Although ETH is a structural analogue of isoniazid, only little
      cross-resistance to these two drugs is observed among clinical isolates. Both
      isoniazid and ETH are pro-drugs that need to be activated by mycobacterial
      enzymes to exert their antimicrobial activity. We have recently identified two M.
      tuberculosis genes, Rv3854c (ethA) and Rv3855 (ethR), involved in resistance to
      ETH. ethA encodes a protein that belongs to the Flavin-containing monooxygenase
      family catalysing the activation of ETH. We show here that ethR, which encodes a
      repressor belonging to the TetR/CamR family of transcriptional regulators,
      negatively regulates the expression of ethA. By the insertion of the ethA
      promoter region upstream of the lacZ reporter gene, overexpression of ethR in
      trans was found to cause a strong inhibition of ethA expression, independently of
      the presence of ETH in the culture media. Electrophoretic mobility shift assays
      indicated that EthR interacts directly with the ethA promoter region. This
      interaction was confirmed by DNA footprinting analysis, which, in addition,
      identified the EthR-binding region. Unlike other TetR/CamR members, which
      typically bind 15 bp operators, EthR recognises an unusually long 55 bp region
      suggesting multimerization of the repressor on its operator. Identification by
      primer-extension of the ethA transcriptional start site indicated that it is
      located within the EthR-binding region. Taken together, bacterial two-hybrid
      experiments and gel filtration assays suggested a dimerization of EthR in the
      absence of its operator. In contrast, surface plasmon resonance analyses showed
      that eight EthR molecules bind cooperatively to the 55 bp operator, which
      represents a novel repression mechanism for a TetR/CamR member.

PMID- 14651621
TI  - Authentic precursors to ribosomal subunits accumulate in Escherichia coli in the
      absence of functional DnaK chaperone.
AB  - Escherichia coli dnaK-ts mutants are defective in the late stages of ribosome
      biogenesis at high temperature. Here, we show that the 21S, 32S and 45S ribosomal
      particles that accumulate in the dnaK756-ts mutant at 44 degrees C contain
      unprocessed forms of their 16S and 23S rRNAs (partially processed in the case of
      45S particles). Their 5S rRNA stoichiometry and ribosomal protein composition are
      typical of the genuine ribosomal precursors found in a wild-type (dnaK+) strain.
      Despite the lack of a functional DnaK, a very slow maturation of these 21S, 32S
      and 45S particles to structurally and functionally normal 30S and 50S ribosomal
      subunits still occurs at high temperature. This conversion is accompanied by the
      processing of p16S and p23S rRNAs to their mature forms. We conclude that: (i)
      21S, 32S and 45S particles are not dead-end particles, but true precursors to
      active ribosomes (21S particles are converted to 30S subunits, and 32S and 45S to
      50S subunits); (ii) DnaK is not absolutely necessary for ribosome biogenesis, but
      accelerates the late steps of this process considerably at high temperature; and
      (iii) 23S rRNA processing depends on the stage reached in the stepwise assembly
      of the 50S subunit, not directly on DnaK.

PMID- 14651622
TI  - Evidence for dynamic clustering of carboxy-terminal aromatic amino acids in TonB
      dependent energy transduction.
AB  - Escherichia coli uses the proton motive force of the cytoplasmic membrane and
      TonB protein to energize the active transport of iron-siderophores and vitamin
      B12 across the outer membrane. TonB shuttles between the cytoplasmic and outer
      membranes, presumably during the course of energy transduction. Previous results
      indicated that the carboxy-terminal 65 amino acids of TonB are essential for both
      its outer membrane association and activity. A highly conserved region (residues
      199-216) within this domain, predicted to be an amphipathic alpha-helix, was the
      initial focus of this study. Scanning mutagenesis indicated that only the
      aromatic residues F202, W213 and Y215 were individually important for activity.
      When the crystal structure of a dimeric TonB carboxy-terminus subsequently became
      available, we observed that two additional aromatic residues outside that region,
      F180 and F230, were potentially engaged in end-on hydrophobic interactions with
      the three residues identified previously. Changing these five aromatic residues
      individually to alanine reduced TonB activity. Surprisingly, however, each
      substitution exhibited a unique phenotypic profile with respect to ability to
      support [55Fe]-ferrichrome transport, sensitivity to colicins B, D, Ia and M or
      sensitivity to bacteriophage phi80. The phenotypic results suggested that the
      carboxy-terminus of TonB was a flexible and dynamic domain that could interact
      specifically with different ligands or transporters, perhaps through the aromatic
      residues. The possibility of interactions among all the aromatic residues was
      tested using double-mutant cycle analysis. All possible combinations of alanine
      substitutions were constructed, with the result that TonB containing any double
      alanine substitution was inactive in the phenotypic assays, while retaining the
      ability to associate with the outer membrane. This synergistic, rather than
      additive, effect of the double mutants suggested that, consistent with the
      flexibility suggested by analysis of the single substitutions, all the aromatic
      residues might be capable of interacting with one another. A means of reconciling
      these results with the crystal structure is presented.

PMID- 14651623
TI  - Lack of O-antigen is essential for plasminogen activation by Yersinia pestis and
      Salmonella enterica.
AB  - The O-antigen of lipopolysaccharide (LPS) is a virulence factor in
      enterobacterial infections, and the advantage of its genetic loss in the lethal
      pathogen Yersinia pestis has remained unresolved. Y. pestis and Salmonella
      enterica express beta-barrel surface proteases of the omptin family that activate
      human plasminogen. Plasminogen activation is central in pathogenesis of plague
      but has not, however, been found to be important in diarrhoeal disease. We
      observed that the presence of O-antigen repeats on wild-type or recombinant S.
      enterica, Yersinia pseudotuberculosis or Escherichia coli prevents plasminogen
      activation by PgtE of S. enterica and Pla of Y. pestis; the O-antigen did not
      affect incorporation of the omptins into the bacterial outer membrane. Purified
      His6-Pla was successfully reconstituted with rough LPS but remained inactive
      after reconstitution with smooth LPS. Expression of smooth LPS prevented Pla
      mediated adhesion of recombinant E. coli to basement membrane as well as invasion
      into human endothelial cells. Similarly, the presence of an O-antigen prevented
      PgtE-mediated bacterial adhesion to basement membrane. Substitution of Arg-138
      and Arg-171 of the motif for protein binding to lipid A 4'-phosphate abolished
      proteolytic activity but not membrane translocation of PgtE, indicating
      dependence of omptin activity on a specific interaction with lipid A. The results
      suggest that Pla and PgtE require LPS for activity and that the O-antigen
      sterically prevents recognition of large-molecular-weight substrates. Loss of O
      antigen facilitates Pla functions and invasiveness of Y. pestis; on the other
      hand, smooth LPS renders plasminogen activator cryptic in S. enterica.

PMID- 14651624
TI  - Genetics of capsule O-acetylation in serogroup C, W-135 and Y meningococci.
AB  - Capsular polysaccharides of serogroup C, W-135 and Y meningococci were previously
      reported to be O-acetylated at the sialic acid residues. There is evidence that O
      acetylation affects the immunogenicity of polysaccharide vaccines. We identified
      genes indispensable for O-acetylation of serogroup C, W-135 and Y meningococci
      downstream of the capsule synthesis genes siaA-D. The genes were co-transcribed
      with the sia operon as shown by reverse transcription polymerase chain reaction
      analysis. The putative capsular polysaccharide O-acetyltransferases were
      designated OatC and OatWY. The protein OatWY of serogroups W-135 and Y showed
      sequence homologies to members of the NodL-LacA-CysE family of bacterial
      acetyltransferases, whereas no sequence homology with any known protein in the
      different databases was found for the serogroup C protein OatC. In serogroup W
      135 and Y meningococci, several clonal lineages either lacked OatWY or OatWY was
      inactivated by insertion of IS1301. For serogroup C meningococci, we observed in
      vitro phase variation of O-acetylation, which resulted from slipped-strand
      mispairing in homopolymeric tracts. This finding explains the observation of
      naturally occurring de-O-acetylated serogroup C meningococci. Our report is the
      first description of sequences of sialic acid O-acetyltransferase genes that have
      not been cloned from either other bacterial or mammalian organisms.

PMID- 14651625
TI  - Modulation of CRP-dependent transcription at the Escherichia coli acsP2 promoter
      by nucleoprotein complexes: anti-activation by the nucleoid proteins FIS and IHF.
AB  - acs encodes acetyl-coenzyme A synthetase, a high-affinity enzyme that allows
      cells to scavenge for acetate during carbon starvation. CRP activates acs
      transcription by binding tandem DNA sites located upstream of the major promoter,
      acsP2. Here, we used electrophoretic mobility shift assays and DNase I footprint
      analyses to demonstrate that the nucleoid proteins FIS and IHF each bind multiple
      sites within the acs regulatory region, that FIS competes successfully with CRP
      for binding to their overlapping and neighbouring sites and that IHF binds
      independently of either FIS or CRP. Using in vitro transcription assays, we
      demonstrated that FIS and IHF independently reduce CRP-dependent acs
      transcription. Using in vivo reporter assays, we showed that disruption of DNA
      sites for FIS or deletion of DNA sites for IHF increases acs transcription. We
      propose that FIS and IHF each function directly as anti-activators of CRP, each
      working independently at different times during growth to set the levels of CRP
      dependent acs transcription.

PMID- 14651626
TI  - The Pasteurella multocida toxin is encoded within a lysogenic bacteriophage.
AB  - Toxigenic strains of Pasteurella multocida produce a 146 kDa toxin (PMT) that
      acts as a potent mitogen. Sequence analysis of the structural gene for PMT, toxA,
      previously suggested it was horizontally acquired, because it had a low G + C
      content relative to the P. multocida genome. To address this, the sequence of DNA
      flanking toxA was determined. The sequence analysis showed the presence of
      homologues to bacteriophage tail protein genes and a bacteriophage antirepressor,
      suggesting that the toxin gene resides within a prophage. In addition to phage
      genes, the toxA flanking DNA contained a homologue of a restriction/modification
      system that was shown to be functional. The presence of a bacteriophage was
      demonstrated in spent medium from toxigenic P. multocida isolates. Its production
      was increased by mitomycin C addition, a treatment that is known to induce the
      lytic cycle of many temperate bacteriophages. The genomes of bacteriophages from
      three different toxigenic P. multocida strains had similar but not identical
      restriction profiles, and were approximately 45-50 kb in length. The prophages
      from two of these had integrated at the same site in the chromosome, in a tRNA
      gene. Southern blot analysis confirmed that these bacteriophages contained the
      toxA gene.

PMID- 14651627
TI  - Characterization of cis-acting prgQ mutants: evidence for two distinct repression
      mechanisms by Qa RNA and PrgX protein in pheromone-inducible enterococcal plasmid
      pCF10.
AB  - The pCF10-encoded negative regulators PrgX and Qa (prgQ antisense) RNA inhibit
      pCF10 transfer by blocking prgQ transcription extension past a potential
      transcription terminator sequence IRS1. To identify potential target sites for
      negative regulation, we isolated and analysed 13 cis-acting mutations in the
      prgXQ region. Determination of the 3' end of Qa RNA showed that eight mutations
      mapped in the region encoding Qa RNA. Four mutations were in the Qa promoter
      region and one was in IRS1. Three mutations in Qa greatly reduced the
      intracellular level of this RNA but did not affect that of PrgX. However, both Qa
      RNA and PrgX protein were reduced in three Qa promoter region mutants and the
      expression of prgQ transcripts extending 3' from IRS1 became constitutive. Qa RNA
      could mediate its negative regulatory activity in the absence of PrgX, and this
      activity was not abolished by cCF10, the peptide pheromone that induces pCF10
      transfer. RNA analysis showed that Qa RNA abolished transcription readthrough.
      Based on the experimental data as well as computer analysis of predicted
      secondary structures of prgQ mRNA in the presence or absence of Qa, we concluded
      that Qa RNA is a pheromone-insensitive effector of prgQ mRNA termination or
      degradation at IRS1. In cells lacking a Qa target sequence, expression of PrgX
      repressed transcription from the prgQ promoter, and this repression was relieved
      by addition of exogenous cCF10. Thus, even though the synthesis of these negative
      regulators is coupled, they each act independently on separate targets to
      regulate expression of conjugation functions.

PMID- 14651628
TI  - Structure-function analysis of the self-recognizing Antigen 43 autotransporter
      protein from Escherichia coli.
AB  - Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia
      coli strains. Expression of Ag43 confers aggregation and fluffing of cells,
      promotes biofilm formation and is associated with enhanced resistance to
      antimicrobial agents. Ag43 is an autotransporter protein and consists of two
      moieties: a transporter, the beta-module, and a passenger domain, the alpha
      module. Here we have employed various molecular approaches to probe
      structure/function aspects of Ag43. An entire family of Ag43 variants was
      identified. The gene encoding Ag43 (flu) was cloned from a diverse range of E.
      coli subtypes and found to encode variant proteins with different properties.
      Several novel variants were identified and characterized that were unable to
      promote cell-cell aggregation. By employing a combination of linker insertion
      mutagenesis and domain swapping between clumping and non-clumping variants, we
      have pinpointed the region of the protein responsible for autoaggregation to be
      located within the N-terminal one-third of the passenger domain. Our data suggest
      that ionic interactions between charged residues residing in interacting pairs of
      Ag43alpha domains may be important for the self-recognition process. Based on its
      similarity to other related proteins, we predict the passenger, Ag43alpha, domain
      primarily to consist of an extended beta-helix structure in which numerous
      repeats or rungs are stacked in parallel orientation in an extended cylindrical
      formation. Finally, we found that in spite of their different aggregative pattern
      all Ag43 variants promoted biofilm formation to abiotic surfaces.

PMID- 14651630
TI  - Cyclophilin A and calcineurin functions investigated by gene inactivation,
      cyclosporin A inhibition and cDNA arrays approaches in the phytopathogenic fungus
      Botrytis cinerea.
AB  - Calcineurin phosphatase and cyclophilin A are cellular components involved in
      fungal morphogenesis and virulence. Their roles were investigated in the
      phytopathogenic fungus Botrytis cinerea using gene inactivation, drug inhibition
      and cDNA macroarrays approaches. First, the BCP1 gene coding for cyclophilin A
      was identified and inactivated by homologous recombination. The bcp1Delta null
      mutant obtained was still able to develop infection structures but was altered in
      symptom development on bean and tomato leaves. Opposite to this, calcineurin
      inhibition using cyclosporin A (CsA) modified hyphal morphology and prevented
      infection structure formation. CsA drug pattern signature on macroarrays allowed
      the identification of 18 calcineurin-dependent (CND) genes among 2839 B. cinerea
      genes. Among the co-regulated CND genes, three were shown to be organized as a
      physical cluster that could be involved in secondary metabolism. The signature of
      BCP1 inactivation on macroarrays allowed the identification of only three BCP1
      cyclophilin-dependent (CPD) genes that were different from CND genes. Finally, no
      CsA drug pattern signature was observed in the bcp1Delta null mutant which
      provided a molecular target validation of the drug.

PMID- 14651631
TI  - Stop codon recognition and interactions with peptide release factor RF3 of
      truncated and chimeric RF1 and RF2 from Escherichia coli.
AB  - Release factors RF1 and RF2 recognize stop codons present at the A-site of the
      ribosome and activate hydrolysis of peptidyl-tRNA to release the peptide chain.
      Interactions with RF3, a ribosome-dependent GTPase, then initiate a series of
      reactions that accelerate the dissociation of RF1 or RF2 and their recycling
      between ribosomes. Two regions of Escherichia coli RF1 and RF2 were identified
      previously as involved in stop codon recognition and peptidyl-tRNA hydrolysis. We
      show here that removing the N-terminal domain of RF1 or RF2 or exchanging this
      domain between the two factors does not affect RF specificity but has different
      effects on the activity of RF1 and RF2: truncated RF1 remains highly active and
      able to support rapid cell growth, whereas cells with truncated RF2 grow only
      poorly. Transplanting a loop of 13 amino acid residues from RF2 to RF1 switches
      the stop codon specificity. The interaction of the truncated factors with RF3 on
      the ribosome is defective: they fail to stimulate guanine nucleotide exchange on
      RF3, recycling is not stimulated by RF3, and nucleotide-free RF3 fails to
      stabilize the binding of RF1 or RF2 to the ribosome. However, the N-terminal
      domain seems not to be required for the expulsion of RF1 or RF2 by RF3:GTP.

PMID- 14651632
TI  - Modulation of Pseudomonas aeruginosa gene expression by host microflora through
      interspecies communication.
AB  - The change in gene expression patterns in response to host environments is a
      prerequisite for bacterial infection. Bacterial diseases often occur as an
      outcome of the complex interactions between pathogens and the host. The
      indigenous, usually non-pathogenic microflora is a ubiquitous constituent of the
      host. In order to understand the interactions between pathogens and the resident
      microflora and how they affect the gene expression patterns of the pathogens and
      contribute to bacterial diseases, the interactions between pathogenic Pseudomonas
      aeruginosa and avirulent oropharyngeal flora (OF) strains isolated from sputum
      samples of cystic fibrosis (CF) patients were investigated. Animal experiments
      using a rat lung infection model indicate that the presence of OF bacteria
      enhanced lung damage caused by P. aeruginosa. Genome-wide transcriptional
      analysis with a lux reporter-based promoter library demonstrated that
      approximately 4% of genes in the genome responded to the presence of OF strains
      using an in vitro system. Characterization of a subset of the regulated genes
      indicates that they fall into seven functional classes, and large portions of the
      upregulated genes are genes important for P. aeruginosa pathogenesis. Autoinducer
      2 (AI-2)-mediated quorum sensing, a proposed interspecies signalling system,
      accounted for some, but not all, of the gene regulation. A substantial amount of
      AI-2 was detected directly in sputum samples from CF patients and in cultures of
      most non-pseudomonad bacteria isolated from the sputa. Transcriptional profiling
      of a set of defined P. aeruginosa virulence factor promoters revealed that OF and
      exogenous AI-2 could upregulate overlapping subsets of these genes. These results
      suggest important contributions of the host microflora to P. aeruginosa infection
      by modulating gene expression via interspecies communications.

PMID- 14651633
TI  - The distribution of RNA polymerase in Escherichia coli is dynamic and sensitive
      to environmental cues.
AB  - Despite extensive genetic, biochemical and structural studies on Escherichia coli
      RNA polymerase (RNAP), little is known about its location and distribution in
      response to environmental changes. To visualize the RNAP by fluorescence
      microscopy in E. coli under different physiological conditions, we constructed a
      functional rpoC-gfp gene fusion on the chromosome. We show that, although RNAP is
      located in the nucleoid and at its periphery, the distribution of RNAP is dynamic
      and dramatically influenced by cell growth conditions, nutrient starvation and
      overall transcription activity inside the cell. Moreover, mutational analysis
      suggests that the stable RNA synthesis plays an important role in nucleoid
      condensation.

PMID- 14651634
TI  - Deletion analysis identifies key functional domains of the cytadherence
      associated protein HMW2 of Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae attachment to host cells requires biogenesis of a
      functional attachment organelle, including proper localization of the adhesion
      protein P1 to this structure. Mutations in the hmw2 gene result in the inability
      to cytadhere, failure to localize P1 to the attachment organelle, altered cell
      morphology and accelerated turnover of the cytadherence-associated proteins HMW1,
      HMW3 and P65. The hmw2 gene encodes HMW2 (190 kDa) and P28 (28 kDa), the latter
      apparently the product of internal translation initiation near the 3' end of the
      hmw2 coding region. Transformation of hmw2 mutant I-2 with recombinant wild-type
      hmw2 restores a wild-type phenotype. In the current study, a severely truncated
      hmw2 gene with an in frame internal deletion of 80% of the HMW2 coding region
      that leaves the P28-encoding region intact restored cytadherence to mutant I-2.
      Transformants produced the expected 38 kDa HMW2 derivative (HMW2Deltamid) at
      levels comparable to that of HMW2 in wild-type cells; like HMW2, HMW2Deltamid
      exhibited marked Triton X-100 insolubility. HMW3, P65 and P28 were fully
      restored, but not HMW1. These transformants were morphologically similar to wild
      type M. pneumoniae but failed to localize P1 to the attachment organelle.
      Finally, a C-terminally truncated HMW2 derivative was partly Triton X-100 soluble
      and incapable of restoring HMW1, HMW3 and P65 to wild-type levels. These data are
      consistent with a model in which the C-terminal domain of HMW2 imparts normal
      localization to the protein, and this localization itself is required for
      productive interactions with downstream cytadherence-associated proteins.
      Furthermore, these results emphasize the association of HMW1 with P1 clustering.

PMID- 14651635
TI  - Heterologous expression of a mammalian protein tyrosine phosphatase gene in
      Leishmania: effect on differentiation.
AB  - Leishmania is a protozoan pathogen which is transmitted to humans through the
      bite of an infected sandfly. This infection results in a spectrum of diseases
      throughout the developing world, collectively known as leishmaniasis. During its
      life cycle, Leishmania differentiates from the promastigote stage in the sandfly
      vector into the amastigote stage in the mammalian host where it multiplies
      exclusively in macrophage phagolysosomes. Although differentiation of Leishmania
      is essential for its survival and pathogenesis in the mammalian host, this
      process is poorly understood. In higher eukaryotic cells, protein tyrosine
      phosphorylation plays a central role in cell proliferation, differentiation and
      overall function. We have therefore investigated the role of protein tyrosine
      phosphorylation in Leishmania differentiation by undertaking complementary
      approaches to mediate protein tyrosine dephosphorylation in vivo. In the present
      study, L. donovani were engineered to express a mammalian protein tyrosine
      phosphatase, or were treated with inhibitors of protein tyrosine kinases, and the
      resulting phenotype was examined. Both approaches resulted in a partial
      differentiation from promastigotes to amastigotes including the expression of the
      amastigote specific A2 protein, morphological change and increased virulence.
      These data provide support for the involvement of tyrosine phosphorylation in the
      differentiation of Leishmania.

PMID- 14651636
TI  - Evidence for the importance of genetic structuring to the structural and
      functional specialization of the Plasmodium falciparum var gene family.
AB  - The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1)
      proteins that act as virulence factors responsible for both antigenic variation
      and cytoadherence of infected erythrocytes. These proteins orchestrate infected
      erythrocyte sequestration from blood circulation and contribute to adhesion-based
      complications of P. falciparum malaria infections. For this study, we analysed
      the genetic organization and strain structure of var genes and present evidence
      for three separately evolving groups that have, in part, functionally diverged
      and differ between subtelomeric and central chromosomal locations. Our analyses
      suggest that a recombination hierarchy limits reassortment between groups and may
      explain why some var genes are unusually conserved between parasite strains. This
      recombination hierarchy, coupled with binding and immune selection, shapes the
      variant antigen repertoire and has structural, functional and evolutionary
      consequences for the PfEMP1 protein family that are directly relevant to malaria
      pathogenesis.

PMID- 14651637
TI  - Malaria parasites lacking eef1a have a normal S/M phase yet grow more slowly due
      to a longer G1 phase.
AB  - Eukaryotic elongation factor 1A (eEF1A) plays a central role in protein
      synthesis, cell growth and morphology. Malaria parasites possess two identical
      genes encoding eEF1A (eef1aa and eef1ab). Using pbeef1a-Plasmodium berghei
      mutants that lack an eEF1a gene, we demonstrate that the level of eEF1A
      production affects the proliferation of blood stages and parasite fitness.
      Pbeef1a- parasites can complete the vertebrate and mosquito phases of the life
      cycle, but the growth phase of the asexual blood stages is extended by up to 20%.
      Analysis of the cell cycle by flow cytometry as well as transcriptional analyses
      revealed that the duration of the S and M phases and the number of daughter cells
      produced were not detectably affected, but that the G1 phase is elongated. Thus,
      as in budding yeast, a growth threshold must be achieved by blood-stage
      Plasmodium parasites to permit transition from G1 into S/M phase. Initial
      analyses indicate that transcriptional events associated with gametocyte
      development were not remarkably retarded. Insight into protein synthesis and its
      influence on cell proliferation might be used to generate slow-growing
      (attenuated) parasites.

PMID- 14651638
TI  - Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector
      called Cif, which blocks cell cycle G2/M transition.
AB  - Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC)
      are closely related pathogens. Both use a type III secretion system (TTSS)
      encoded by the 'locus of enterocyte effacement' (LEE) to subvert and attach to
      epithelial cells through the injection of a repertoire of effector molecules.
      Here, we report the identification of a new TTSS translocated effector molecule
      called Cif, which blocks cell cycle G2/M transition and induces the formation of
      stress fibres through the recruitment of focal adhesions. Cif is not encoded by
      the LEE but by a lambdoid prophage present in EPEC and EHEC. A cif mutant causes
      localized effacement of microvilli and intimately attaches to the host cell
      surface, but is defective in the ability to block mitosis. When expressed in TTSS
      competent LEE-positive pathogens, Cif is injected into the infected epithelial
      cells. These cells arrested at the G2/M phase displayed accumulation of inactive
      phosphorylated Cdk1. In conclusion, Cif is a new member of a growing family of
      bacterial cyclomodulins that subvert the host eukaryotic cell cycle.

PMID- 14651639
TI  - Distribution of split DnaE inteins in cyanobacteria.
AB  - Inteins are genetic elements found inside the coding regions of different host
      proteins and are translated in frame with them. The intein-encoded protein region
      is removed by an autocatalytic protein-splicing reaction that ligates the host
      protein flanks with a peptide bond. This reaction can also occur in trans with
      the intein and host protein split in two. After translation of the two genes, the
      two intein parts ligate their flanking protein parts to each other, producing the
      mature protein. Naturally split inteins are only known in the DNA polymerase III
      alpha subunit (polC or dnaE gene) of a few cyanobacteria. Analysing the
      phylogenetic distribution and probable genetic propagation mode of these split
      inteins, we conclude that they are genetically fixed in several large
      cyanobacterial lineages. To test our hypothesis, we sequenced parts of the dnaE
      genes from five diverse cyanobacteria and found all species to have the same type
      of split intein. Our results suggest the occurrence of a genetic rearrangement in
      the ancestor of a large division of cyanobacteria. This event fixed the dnaE gene
      in a unique two-genes one-protein configuration in the progenitor of many
      cyanobacteria. Our hypothesis, findings and the cloning procedure that we
      established allow the identification and acquisition of many naturally split
      inteins. Having a large and diverse repertoire of these unique inteins will
      enable studies of their distinct activity and enhance their use in biotechnology.

PMID- 14651640
TI  - Temperature effect on inclusion body formation and stress response in the
      periplasm of Escherichia coli.
AB  - We previously characterized a defective-folding mutant of maltose-binding protein
      of Escherichia coli, MalE31, which formed periplasmic inclusion bodies. Here, we
      show that MalE31 aggregation does not affect bacterial growth at 30 degrees C but
      is lethal at 37 degrees C. Surprisingly, under mild heat shock conditions at 42
      degrees C, inclusion bodies are degraded and bacterial growth is restored. One
      physiological consequence for the cells overproducing MalE31 was to induce an
      extracytoplasmic stress response by increasing the expression of the heat shock
      protease DegP via the CpxA/CpxR two-component signalling pathway. Furthermore, we
      show that the Cpx response is required to rescue the cells from the toxicity
      mediated by MalE31. Finally, expression of highly destabilized MalE variants that
      do not aggregate in the periplasm also induces the Cpx pathway, indicating that
      inclusion body formation is not necessary to activate this specific
      extracytoplasmic stress regulatory system.

PMID- 14651642
TI  - Ssh10b, a conserved thermophilic archaeal protein, binds RNA in vivo.
AB  - Proteins of the Sac10b family, which is highly conserved among hyperthermophilic
      archaea, have been regarded as DNA-binding proteins. Based on their in vitro DNA
      binding properties, these proteins are thought to be involved in chromosomal
      organization or DNA repair/recombination. We show that Ssh10b, a member of the
      Sac10b family from Sulfolobus shibatae, bound with similar affinities to double
      stranded DNA, single-stranded DNA and RNA in vitro. However, the protein was
      exclusively bound to RNA in S. shibatae cells, as revealed by in vivo UV cross
      linking and co-immunoprecipitation. Ribosomal RNAs were among the RNA species co
      immunoprecipitated with Ssh10b. Consistent with this observation, Ssh10b was co
      purified with ribosomes under low salt conditions. Furthermore, we demonstrate by
      UV-cross-linking hybridization that, when the cells were irradiated with UV,
      Ssh10b became cross-linked to 16S, 23S rRNAs and mRNAs. Our data indicate that
      RNA is the physiological binding target of the Sac10b family.

PMID- 14651641
TI  - Cell wall stress responses in Bacillus subtilis: the regulatory network of the
      bacitracin stimulon.
AB  - In response to sublethal concentrations of antibiotics, bacteria often induce an
      adaptive response that can contribute to antibiotic resistance. We report the
      response of Bacillus subtilis to bacitracin, an inhibitor of cell wall
      biosynthesis found in its natural environment. Analysis of the global
      transcriptional profile of bacitracin-treated cells reveals a response
      orchestrated by two alternative sigma factors (sigmaB and sigmaM) and three two
      component systems (YvqEC, YvcPQ and BceRS). All three two-component systems are
      located next to target genes that are strongly induced by bacitracin, and the
      corresponding histidine kinases share an unusual topology: they lack about 100
      amino acids in their extracellular sensing domain, which is almost entirely
      buried in the cytoplasmic membrane. Sequence analysis indicates that this novel N
      terminal sensing domain is a characteristic feature of a subfamily of histidine
      kinases, found almost entirely in Gram-positive bacteria and frequently linked to
      ABC transporters. A systematic mutational analysis of bacitracin-induced genes
      led to the identification of a new bacitracin-resistance determinant, bceAB,
      encoding a putative ABC transporter. The bcrC bacitracin resistance gene, which
      is under the dual control of sigmaX and sigmaM, was also induced by bacitracin.
      By comparing the bacitracin and the vancomycin stimulons, we can differentiate
      between loci induced specifically by bacitracin and those that are induced by
      multiple cell wall-active antibiotics.

PMID- 14651643
TI  - Use of green fluorescent protein fusions to analyse the N- and C-terminal signal
      peptides of GPI-anchored cell wall proteins in Candida albicans.
AB  - Glycophosphatidylinositol (GPI)-anchored proteins account for 26-35% of the
      Candida albicans cell wall. To understand the signals that regulate these
      proteins' cell surface localization, green fluorescent protein (GFP) was fused to
      the N- and C-termini of the C. albicans cell wall proteins (CWPs) Hwp1p, Als3p
      and Rbt5p. C. albicans expressing all three fusion proteins were fluorescent at
      the cell surface. GFP was released from membrane fractions by PI-PLC and from
      cell walls by beta-glucanase, which implied that GFP was GPI-anchored to the
      plasma membrane and then covalently attached to cell wall glucans. Twenty and 25
      amino acids, respectively, from the N- and C-termini of Hwp1p were sufficient to
      target GFP to the cell surface. C-terminal substitutions that are permitted by
      the omega rules (G613D, G613N, G613S, G613A, G615S) did not interfere with GFP
      localization, whereas some non-permitted substitutions (G613E, G613Q, G613R,
      G613T and G615Q) caused GFP to accumulate in intracellular ER-like structures and
      others (G615C, G613N/G615C and G613D/G615C) did not. These results imply that (i)
      GFP fusions can be used to analyse the N- and C-terminal signal peptides of GPI
      anchored CWPs, (ii) the omega amino acid in Hwp1p is G613, and (iii) C can
      function at the omega+2 position in C. albicans GPI-anchored proteins.

PMID- 14651644
TI  - The AGUAAA motif in cspA1/A2 mRNA is important for adaptation of Yersinia
      enterocolitica to grow at low temperature.
AB  - Acclimatization of the psychrotolerant Yersinia enterocolitica after a cold shock
      from 30 degrees C to 10 degrees C causes transcription of the major cold shock
      protein (CSP) bicistronic gene cspA1/A2 to increase by up to 300-fold. Northern
      blot analysis of cspA1/A2 using four probes that hybridize specifically to
      different regions of CSP mRNA revealed the appearance of a number of cspA1/A2
      transcripts that are smaller than the original transcript and transiently visible
      at the end of the acclimation period. Primer extension and RNA protection
      experiments demonstrated that these smaller mRNAs have 5' ends located in the
      same core sequence (5'-AGUAAA-3') at five different places within the mRNA,
      indicating preferential cleavage of the CSP mRNA transcripts. A similar result
      was obtained for cspB of Escherichia coli, containing two such core sequences.
      Furthermore, this motif is present in the major CSP genes of a variety of Gram
      negative and Gram-positive bacteria. We have therefore termed this sequence cold
      shock cut box (CSC-box). After inserting a CSC-box into a plasmid-bound lacZ gene
      in Y. enterocolitica, the mRNA of this construct was cleaved within the CSC-box,
      and a change in this CSC-box from AGUAAA to AGUCCC dramatically reduced cleavage
      of the mutated lacZ gene. Mutating all CSC-boxes in Y. enterocolitica of a
      plasmid bound cspA1/A2 dramatically increases the lag time after a cold shock
      before re-growth occurs. Based on these results, we suggest that the role of the
      CSC-box is related to downregulation of cspA mRNA after acclimation to low
      temperature.

PMID- 14651645
TI  - Constitutive expression of PcsB suppresses the requirement for the essential VicR
      (YycF) response regulator in Streptococcus pneumoniae R6.
AB  - We report several new findings about the function of the essential VicRK two
      component regulatory system (TCS) in the human pathogen Streptococcus pneumoniae.
      The vicR-encoded response regulator, vicK-encoded histidine kinase and the
      protein encoded by the downstream vicX gene are the homologues of the YycF, YycG
      and YycJ proteins, respectively, studied previously in Bacillus subtilis and
      Staphylococcus aureus. Using a regulatable promoter, we demonstrated that the
      VicK histidine kinase is conditionally required for growth of S. pneumoniae.
      Likewise, we found that the VicX protein is also conditionally required for
      growth and probably plays a role in the essential signal transduction pathway
      mediated by VicR and VicK. Recovery of limited substitutions in the conserved
      aspartate 52 residue (D52) of VicR was consistent with a requirement for
      phosphorylation of VicR for growth under some conditions. We applied microarrays
      to characterize the changes in transcription patterns in bacteria depleted for
      vicRKX operon expression. Our results suggest that the pcsB gene is a target of
      the VicRK TCS. We present evidence that downregulation of pcsB could account for
      many of the defects in cell growth, shape, size and morphology observed in
      bacteria depleted for vicRKX expression. Furthermore, constitutive expression of
      pcsB+ suppressed the essential requirement for the VicRK TCS and allowed the
      isolation of vicR null mutants.

PMID- 14651646
TI  - The RcsC sensor kinase is required for normal biofilm formation in Escherichia
      coli K-12 and controls the expression of a regulon in response to growth on a
      solid surface.
AB  - Bacteria are often found associated with surfaces as sessile bacterial
      communities called biofilms, and the formation of a biofilm can be split up into
      different stages each requiring the expression of specific genes. The production
      of extracellular polysaccharides (EPS) is important for the maturation of
      biofilms and is controlled by the Rcs two-component pathway in Escherichia coli
      (and other Gram-negative bacteria). In this study, we show, for the first time,
      that the RcsC sensor kinase is required for normal biofilm development in E.
      coli. Moreover, using a combination of DNA macroarray technology and
      transcriptional fusion analysis, we show that the expression of > 150 genes is
      controlled by RcsC in E. coli. In silico analyses of the RcsC regulon predicts
      that 50% of the genes encode proteins that are either localized to the envelope
      of E. coli or have activities that affect the structure/properties of the
      bacterial surface, e.g. the production of colanic acid. Moreover, we also show
      that RcsC is activated during growth on a solid surface. Therefore, we suggest
      that the RcsC sensor kinase may play an important role in the remodelling of the
      bacterial surface during growth on a solid surface and biofilm formation.

PMID- 14651647
TI  - The Spo0A regulon of Bacillus subtilis.
AB  - The master regulator for entry into sporulation in Bacillus subtilis is the DNA
      binding protein Spo0A, which has been found to influence, directly or indirectly,
      the expression of over 500 genes during the early stages of development. To
      search on a genome-wide basis for genes under the direct control of Spo0A, we
      used chromatin immunoprecipitation in combination with gene microarray analysis
      to identify regions of the chromosome at which an activated form of Spo0A binds
      in vivo. This information in combination with transcriptional profiling using
      gene microarrays, gel electrophoretic mobility shift assays, using the DNA
      binding domain of Spo0A, and bioinformatics enabled us to assign 103 genes to the
      Spo0A regulon in addition to 18 previously known members. Thus, in total, 121
      genes, which are organized as 30 single-gene units and 24 operons, are likely to
      be under the direct control of Spo0A. Forty of these genes are under the positive
      control of Spo0A, and 81 are under its negative control. Among newly identified
      members of the regulon with transcription that was stimulated by Spo0A are genes
      for metabolic enzymes and genes for efflux pumps. Among members with
      transcription that was in-hibited by Spo0A are genes encoding components of the
      DNA replication machinery and genes that govern flagellum biosynthesis and
      chemotaxis. Also in-cluded in the regulon are many (25) genes with products that
      are direct or indirect regulators of gene transcription. Spo0A is a master
      regulator for sporulation, but many of its effects on the global pattern of gene
      transcription are likely to be mediated indirectly by regulatory genes under its
      control.

PMID- 14651648
TI  - Mitochondrial and Wolbachia markers for the sandfly Phlebotomus papatasi: little
      population differentiation between peridomestic sites and gerbil burrows in
      Isfahan province, Iran.
AB  - In Iran, Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) is the main vector
      of Leishmania major Yakimoff & Schokhor (Kinetoplastida: Trypanosomatidae), the
      causative agent of rural zoonotic cutaneous leishmaniasis. This sandfly is
      abundant both in villages and in the burrows of the main reservoir host, the
      gerbil Rhombomys opimus (Licht.) (Rodentia: Gerbillidae). Populations of P.
      papatasi were sampled from the edges of villages in Isfahan province, using CDC
      miniature light traps in peridomestic sites and sticky papers placed at the
      entrances to gerbil burrows. Single peridomestic sites in two northern provinces
      were also sampled. Individual sandflies were characterized by PCR amplification
      and sequencing of fragments of their mitochondrial cytochrome b gene and of the
      wsp gene of endosymbiotic Wolbachia pipientis Hertig (alpha-Proteobacteria:
      Rickettsiaceae). The distributions of the haplotypes of these two maternally
      inherited genes were analysed to assess the population differentiation of P.
      papatasi, knowledge of which will be needed for planning control measures. For
      the first time these markers were used to characterize P. papatasi from gerbil
      burrows, and they indicated the absence not only of sympatric cryptic species but
      also of any long-term differentiation of lineages in different habitats. A single
      lineage of cytochrome b haplotypes was found, and both sexes in all populations
      had a high infection rate of the same A-group strain of Wolbachia (wPap). The
      distributions of cytochrome b haplotypes were consistent with females dispersing
      more than males, which has been reported for P. papatasi in other countries. The
      widespread distribution of wPap suggests that Wolbachia could be used to spread
      transgenes between populations of P. papatasi in different habitats.

PMID- 14651649
TI  - Molecular identification of some forensically important blowflies of southern
      Africa and Australia.
AB  - One major aspect of research in forensic entomology is the investigation of
      molecular techniques for the accurate identification of insects. Studies to date
      have addressed the corpse fauna of many geographical regions, but generally
      neglected the southern African calliphorid species. In this study, forensically
      significant calliphorids from South Africa, Swaziland, Botswana and Zimbabwe and
      Australia were sequenced over an 1167 base pair region of the COI gene.
      Phylogenetic analysis was performed to examine the ability of the region to
      resolve species identities and taxonomic relationships between species. Analyses
      by neighbour-joining, maximum parsimony and maximum likelihood methods all showed
      the potential of this region to provide the necessary species-level
      identifications for application to post-mortem interval (PMI) estimation;
      however, higher level taxonomic relationships did vary according to method of
      analysis. Intraspecific variation was also considered in relation to determining
      suitable maximum levels of variation to be expected during analysis. Individuals
      of some species in the study represented populations from both South Africa and
      the east coast of Australia, yet maximum intraspecific variation over this gene
      region was calculated at 0.8%, with minimum interspecific variation at 3%,
      indicating distinct ranges of variation to be expected at intra- and
      interspecific levels. This region therefore appears to provide southern African
      forensic entomologists with a new technique for providing accurate identification
      for application to estimation of PMI.

PMID- 14651650
TI  - In vitro assays for repellents and deterrents for ticks: differing effects of
      products when tested with attractant or arrestment stimuli.
AB  - Most in vivo and in vitro tests with repellents or deterrents against ticks have
      not considered which sensory channel is being targeted. We have recorded the
      responses of two hard tick species (Acari: Ixodidae) in vitro to determine if
      such products can disrupt the perception of an attractant in a repellent assay or
      the perception of an arrestment stimulus in a deterrent assay. Ethyl
      butylacetylaminopropionate (EBAAP), N,N-diethyl-methyl-benzamide (deet),
      permethrin and indalone were chosen to test their capacity to inhibit the
      attraction of Amblyomma variegatum Fabricius to its aggregation-attachment
      pheromone. Vapours of each test product plus those from a synthetic blend of the
      pheromone were delivered to the walking tick in an air stream on a locomotion
      compensator. Neither EBAAP, deet, permethrin nor indalone could inhibit
      attraction of A. variegatum even when each of the test products was delivered at
      106 times the pheromone. Indalone did decrease the attraction of A. variegatum to
      the pheromone and induced repulsion of A. variegatum when presented on its own in
      the air stream. The effect of permethrin, a sodium channel blocker, was also
      tested in a deterrent assay measuring the arrestment of Ixodes ricinus (L.)
      adults on its own faeces and faecal constituents. Permethrin deterred arrestment
      at doses of 670 fg/cm2 to 67 ng/cm2, i.e. at levels five times lower than the
      dose of chemostimuli present in the arrestment stimulus. This sensitivity to
      permethrin suggests that it acts via the contact chemoreception channel.

PMID- 14651651
TI  - Phylogenetic status and matrilineal structure of the biting midge, Culicoides
      imicola, in Portugal, Rhodes and Israel.
AB  - The biting midge Culicoides imicola Kieffer (Diptera: Ceratopogonidae) is the
      most important Old World vector of African horse sickness (AHS) and bluetongue
      (BT). Recent increases of BT incidence in the Mediterranean basin are attributed
      to its increased abundance and distribution. The phylogenetic status and genetic
      structure of C. imicola in this region are unknown, despite the importance of
      these aspects for BT epidemiology in the North American BT vector. In this study,
      analyses of partial mitochondrial cytochrome oxidase subunit I gene (COI)
      sequences were used to infer phylogenetic relationships among 50 C. imicola from
      Portugal, Rhodes, Israel, and South Africa and four other species of the Imicola
      Complex from southern Africa, and to estimate levels of matrilineal subdivision
      in C. imicola between Portugal and Israel. Eleven haplotypes were detected in C.
      imicola, and these formed one well-supported clade in maximum likelihood and
      Bayesian trees implying that the C. imicola samples comprise one phylogenetic
      species. Molecular variance was distributed mainly between Portugal and Israel,
      with no haplotypes shared between these countries, suggesting that female
      mediated gene flow at this scale has been either limited or non-existent. Our
      results provide phylogenetic evidence that C. imicola in the study areas are
      potentially competent AHS and BT vectors. The geographical structure of the C.
      imicola COI haplotypes was concordant with that of BT virus serotypes in recent
      BT outbreaks in the Mediterranean basin, suggesting that population subdivision
      in its vector can impose spatial constraints on BT virus transmission.

PMID- 14651652
TI  - Geographical and seasonal distribution of the bluetongue virus vector, Culicoides
      imicola, in central Italy.
AB  - Following the first incursion of bluetongue virus (BTV) into Italy, the
      geographical and seasonal distribution of the biting midge Culicoides imicola
      Kieffer (Diptera: Ceratopogonidae), the main vector of BTV and African horse
      sickness virus, was investigated in two regions of central Italy (Lazio and
      Tuscany). Surveillance of Culicoides was carried out between July 2001 and
      December 2002 using light traps: 1917 collections were made in 381 trap sites,
      well distributed across both regions. During the survey, bluetongue outbreaks
      were recorded in both regions. Culicoides imicola was found in 89 (23%) trap
      sites, distributed fairly continuously along the whole western coastline, between
      41.2697 degrees N and 44.05724 degrees N. It was found only occasionally inland
      and usually in low abundance, with catches of more than 1000 specimens per night
      found in only two sample sites and 74% of catches numbering fewer than 10
      specimens. Adults were caught from March to mid December, with peaks ranging from
      the end of August to mid November. The coastal distribution and the presence of
      only few sites with year-round records of adult vectors suggests that
      colonization may have occurred recently, by passive wind-dispersal from external
      source areas (Sardinia and Corsica). Alternatively, the species may occur in
      established, previously undetected, autochthonous populations that are limited
      from extension inland and northern-ward within Lazio and Tuscany by cool winter
      temperatures.

PMID- 14651653
TI  - Vasodilatory activity in horsefly and deerfly salivary glands.
AB  - Salivary gland extract (SGE) of four horsefly species (Hybomitra bimaculata
      Macquart, Hybomitra ciureai Seguy, Tabanus bromius L., Tabanus glaucopis Meigen)
      and one deerfly species (Chrysops relictus Meigen) (Diptera: Tabanidae) were
      shown to contain vasodilatory activity. Aliquots equivalent to 1, 5 and 10 pairs
      of salivary glands (SG) relaxed rat femoral artery (with intact endothelium) pre
      constricted with phenylephrine. Vasodilatory activity was dose-dependent. SGE of
      one horsefly species (Haematopota pluvialis L.) did not induce relaxation. The
      kinetics of vasodilation induced by SGE of four horsefly species differed from
      the deerfly. These results indicate that tabanid species may produce more than
      one type of vasodilator to aid blood feeding.

PMID- 14651654
TI  - Mosquito host-feeding patterns and implications for Japanese encephalitis virus
      transmission in northern Australia and Papua New Guinea.
AB  - Japanese encephalitis (JE) virus spread to northern Australia during the 1990s,
      transmitted by Culex annulirostris Skuse and other mosquitoes (Diptera:
      Culicidae). To determine the relative importance of various hosts for potential
      vectors of JE virus, we investigated the host-feeding patterns of mosquitoes in
      northern Australia and Western Province of Papua New Guinea, with particular
      attention to pigs, Sus scrofa L. - the main amplifying host of JE virus in South
      east Asia. Mosquitoes were collected by CDC light traps baited with dry ice and 1
      octen-3-ol, run 16.00-08.00 hours, mostly set away from human habitations, if
      possible in places frequented by feral pigs. Bloodmeals of 2569 mosquitoes,
      representing 15 species, were identified by gel diffusion assay. All species had
      fed mostly on mammals: only <10% of bloodmeals were from birds. The predominant
      species was Cx. annulirostris (88%), with relatively few (4.4%) bloodmeals
      obtained from humans. From all 12 locations sampled, the mean proportion of Cx.
      annulirostris fed on pigs (9.1%) was considerably lower than fed on other animals
      (90.9%). Highest rates of pig-fed mosquitoes (>30%) were trapped where domestic
      pigs were kept close to human habitation. From seven of eight locations on the
      Australian mainland, the majority of Cx. annulirostris had obtained their
      bloodmeals from marsupials, probably the Agile wallaby Macropus agilis (Gould).
      Overall proportions of mosquito bloodmeals identified as marsupial were 60% from
      the Gulf Plains region of Australia, 78% from the Cape York Peninsula and 64%
      from the Daru area of Papua New Guinea. Thus, despite the abundance of feral pigs
      in northern Australia, our findings suggest that marsupials divert host-seeking
      Cx. annulirostris away from pigs. As marsupials are poor JE virus hosts, the
      prevalence of marsupials may impede the establishment of JE virus in Australia.

PMID- 14651655
TI  - Seasonal dynamics of the Cayenne tick, Amblyomma cajennense on horses in Brazil.
AB  - The population dynamics of all stages of the Cayenne tick, Amblyomma cajennense
      (Fabricius) (Acari: Ixodidae) on horses was evaluated over a period of 2 years in
      the district of Pedro Leopoldo, State of Minas Gerais, Brazil. Every 14 days, the
      left side of 20 horses was brushed for collection of immature stages; counts of
      adults were also undertaken. Infestation by larvae was detected from April to
      August, whereas nymphs were observed from June to October. Infestation by adults
      was detected throughout the year, and the highest population density occurred
      from September to March. The number of males was always higher than the number of
      females, but with considerable reduction in the male : female ratio between April
      and July. It was observed that 25% of the horses carried 41% of the infesting
      ticks, and 20% carried only 10% of the ticks during the entire period of the
      study.

PMID- 14651656
TI  - Anopheles arabiensis and An. quadriannulatus resistance to DDT in South Africa.
AB  - The malaria control programme of KwaZulu-Natal Province, South Africa, includes
      Mamfene and Mlambo communities. Western-type houses there are currently sprayed
      with deltamethrin, whereas traditional houses are sprayed with DDT for malaria
      control. In 2002, mosquitoes of the Anopheles gambiae complex (Diptera:
      Culicidae) were collected from DDT-sprayed houses, by window exit traps, and from
      man-baited nets outdoors. Larval collections were also carried out at Mzinweni
      Pan near Mlambo. Species of the An. gambiae complex were identified by rDNA
      polymerase chain reaction assay. The majority of samples collected by window trap
      and baited nets were identified as the malaria vector An. arabiensis Patton, with
      a few An. merus Donitz and An. quadriannulatus (Theobald). The larval collections
      were predominantly An. quadriannulatus with a small number of An. arabiensis.
      Standard WHO insecticide susceptibility tests using 4% DDT and 0.05% deltamethrin
      were performed on both wild-caught females and laboratory-reared progeny from
      wild-caught females. Wild-caught An. arabiensis samples from window traps gave
      63% and 100% mortality 24-h post-exposure to DDT or deltamethrin, respectively.
      Wild-caught An. arabiensis samples from man-baited net traps gave 81% mortality
      24-h post-exposure to DDT. The F1 progeny from 22 An. arabiensis females showed
      average mortality of 86.5% 24-h post-exposure to DDT. Less than 80% mortality was
      recorded from five of these families. Biochemical analyses of samples from each
      of the families revealed comparatively high levels of glutathione-S-transferases
      and non-specific esterases in some families, but without significant correlation
      to bioassay results. Wild-caught An. quadriannulatus larvae were reared through
      to adults and assayed on 4% DDT, giving 47% (n = 36) mortality 24-h post
      exposure. Finding DDT resistance in the vector An. arabiensis, close to the area
      where we previously reported pyrethroid-resistance in the vector An. funestus
      Giles, indicates an urgent need to develop a strategy of insecticide resistance
      management for the malaria control programmes of southern Africa.

PMID- 14651657
TI  - Multiplex PCR assay for malaria vector Anopheles minimus and four related species
      in the Myzomyia Series from Southeast Asia.
AB  - Mosquitoes (Diptera: Culicidae) of the Anopheles (Cellia) Myzomyia Series are
      important malaria vectors in Africa, India and Southeast Asia. Among 10 named
      species of Myzomyia known from the Oriental Region, seven form the An. minimus
      group. Even for expert taxonomists, the adults of these species remain difficult
      to identify morphologically. For technical staff of malaria control programmes,
      confusion may extend to misidentification of species that are not formally within
      the minimus group. For identification of specimens from Indochina (Cambodia,
      Laos, Vietnam), we describe a multiplex polymerase chain reaction (PCR) assay,
      based on rDNA internal transcribed spacer 2 (ITS2) sequences, that employs a
      cocktail of primers to identify An. minimus Theobald sibling species A and C
      (sensu; Green et al., 1990) and three other species in the An. minimus group (An.
      aconitus Donitz, An. pampanai Buttiker & Beales, An. varuna Iyengar), as well as
      An. jeyporiensis James, also belonging to the Myzomyia Series. As the test is DNA
      based, it can be applied to all life stages of these mosquitoes for ecological
      investigations and vector incrimination studies. This PCR assay is simpler,
      quicker, cheaper and more readily interpreted than previous assays.

PMID- 14651658
TI  - Mitochondrial diversity of Musca domestica housefly populations in the Asian and
      western Pacific biogeographical regions.
AB  - Houseflies (Musca domestica L., Diptera: Muscidae) are cosmopolitan, colonizing,
      and eusynanthropic. Their distribution in the Malaysian archipelago provides an
      opportunity to study successive waves of colonization and extinction during the
      Pleistocene and Recent epochs. We scored single-strand conformation polymorphisms
      (SSCPs) at 16S2 and COII mitochondrial loci in 47 housefly samples from the
      Australian, Austro-Malayan, Indo-Malayan, Manchurian and Indo-Chinese subregions
      of Wallace's zoogeographical classification. We discuss the results in light of
      the Pleistocene vs. post-Pleistocene dispersal and faunal exchange in the Asia
      Pacific area. Fourteen haplotypes were detected, of which 10 were confined to a
      single subregion. No haplotype was ubiquitous and only one was found in four
      subregions. Population diversity, HS, was greatest in the Indo-Malayan (0.36) and
      heterogeneous among subregions. The mean subregional diversity was 0.21 +/- 0.03,
      representing the probability that two randomly chosen flies, from any subregion,
      had different haplotypes. The hierarchical partition of diversity indicated
      restricted maternal gene flow among subregions (GRT = 0.60, Nm approximately
      0.32). These results suggest long-standing genetic isolation of houseflies in the
      Malaysian archipelago and support the hypothesis that they dispersed widely
      during the Pleistocene. Haplotypes common among mainland populations but shared
      with island groups in low frequencies (<1%) indicate surprisingly little recent
      gene flow.

PMID- 14651659
TI  - Oral susceptibility of South African Culicoides species to live-attenuated
      serotype-specific vaccine strains of African horse sickness virus (AHSV).
AB  - The oral susceptibility of livestock-associated South African Culicoides midges
      (Diptera: Ceratopogonidae) to infection with the tissue culture-attenuated
      vaccine strains of African horse sickness virus (AHSV) currently in use is
      reported. Field-collected Culicoides were fed on horse blood-virus mixtures each
      containing one of the seven serotype-specific vaccine strains of AHSV, namely
      serotypes 1, 2, 3, 4, 6, 7 and 8. The mean titres of virus in the bloodmeals for
      the seven vaccine strains were between 6.8 and 7.6 log10TCID50/mL. All females (n
      = 3262) that survived 10 days extrinsic incubation (10 dEI) at 23.5 degrees C
      were individually assayed in microplate BHK-21 cell cultures. In midges tested
      immediately after feeding, AHSV was detected in 96.1% individuals; mean virus
      titre was 2.0 log10TCID50/midge. After 10 dEI virus recovery rates varied in
      Culicoides (Avaritia) imicola Kieffer from 1% (AHSV-2) to 11% (AHSV-7) and in
      Culicoides (A.) bolitinos Meiswinkel from 0% (AHSV-3) to 14.6% (AHSV-2). Although
      our results indicate that two major field vectors C. imicola and C. bolitinos are
      susceptible to oral infection with vaccine strains of AHSV, the level of viral
      replication for most of the vaccine strains tested was below the postulated
      threshold (=2.5 log10TCID50/midge) for fully disseminated orbivirus infection. In
      this study, for the first time AHSV has been recovered after 10 dEI from six non
      Avaritia livestock-associated Old World species: C. engubandei de Meillon (AHSV
      4), C. magnus Colaco (AHSV-3, -4), C. zuluensis de Meillon (AHSV-2, -4), C.
      pycnostictus Ingram & Macfie (AHSV-2), C. bedfordi Ingram & Macfie (AHSV-7), and
      C. dutoiti de Meillon (AHSV-7). As little is known about the virogenesis of AHSV
      in the southern African species of Culicoides, the epidemiological significance
      of our findings in relation to the potential for transmission of current AHSV
      vaccine strains by Culicoides requires further assessment.

PMID- 14651660
TI  - First finding of Dirofilaria repens in a natural population of Aedes albopictus.
AB  - The invasive mosquito Aedes albopictus (Skuse) (Diptera: Culicidae) has become
      widespread in Italy during the past decade. Also Italy has foci of canine
      filariasis caused by Dirofilaria (Spirurida: Onchocercidae), due to subcutaneous
      D. repens Railliet & Henry as well as the dog heartworm D. immitis (Leidy)
      transmitted by various vector mosquitoes (Diptera: Culicidae). In 2002, at
      Fiumicino, west of Rome (Lazio Region), 17% of dogs were found to have D. repens
      microfilariae in peripheral blood. To evaluate the role of Ae. albopictus as a
      vector of Dirofilaria in this area, female mosquitoes were collected daily, June
      October 2002, landing on dog or human bait in a rural house at Focene. Mosquitoes
      were maintained at 27 degrees C and 70% RH for 6 days, to allow development or
      purging of filaria larvae, then identified and frozen for subsequent molecular
      assay with filaria-specific ribosomal S2-S16 primers. To distinguish specimens
      harbouring infective L3 Dirofilaria larvae, DNA was extracted separately from the
      mosquito abdomen and head-thorax. Dirofilaria species were identified by
      sequencing, confirmed by polymerase chain reaction of positive specimens using
      primers specific for D. immitis and D. repens. Dirofilaria DNA was detected in
      3/154 (2%) of Ae. albopictus females examined: D. repens DNA in head-thorax and
      abdomen of one collected 27th July; D. immitis in the abdomen of one collected
      24th September; DNA of both D. immitis and D. repens in the head-thorax of one
      collected 11th October 2002. Thus Ae. albopictus is a potential vector of both
      Dirofilarias in Italy, representing risks for veterinary and human health.

PMID- 14651661
TI  - Seasonal abundance patterns of the sandfly Phlebotomus papatasi in climatically
      distinct foci of cutaneous leishmaniasis in Israeli deserts.
AB  - Among foci of cutaneous leishmaniasis in Israel, population densities of the
      vector sandfly Phlebotomus papatasi Scopoli (Diptera: Psychodidae) were assessed
      during April-October 1999 in the mesic Negev desert and the hyper-xeric Arava
      valley, using sticky traps placed overnight near host burrows of the fat sand
      rat, Psammomys obesus Cretzschmar (Cricetidae: Gerbillinae). Population dynamics
      of Ph. papatasi differed between the Negev (study sites on sand near Mount Keren
      and on loess at Nizzana ruins) and the Arava valley (study sites on sand at
      Shezaf and in a fallow field near irrigation at wadi Arava). At the Negev sites,
      sandfly abundance peaked in spring (April or May), whereas at Arava sites Ph.
      papatasi population densities were bi-modal, with peaks in both spring and autumn
      (September or October). This might be conducive to sustaining enzootic Leishmania
      major Yakimoff & Schokhor (Kinetoplastida: Trypanosomatidae). In both areas, Ph.
      papatasi densities were much higher at the site with moister soil, raising
      transmission risks of zoonotic cutaneous leishmaniasis.

PMID- 14651662
TI  - Learning and memory in the mosquito Aedes aegypti shown by conditioning against
      oviposition deterrence.
AB  - Oviposition site choice by female mosquitoes, Aedes aegypti (L) (Diptera:
      Culicidae), was affected by rearing them in water treated with 0.016% of the
      repellent Mozaway trade mark containing citronella and neem. Given a choice
      between a bowl of repellent-treated and a bowl of untreated water, Ae. aegypti
      reared in untreated water strongly preferred to oviposit on the clean water (93
      98%) instead of repellent-treated water. This demonstrates effective deterrence
      of oviposition by dilute Mozaway trade mark. Those reared in repellent-treated
      water were less deterred: 38-46% of their eggs were laid on the repellent-treated
      water and 54-62% on the clean water. Evidently the female mosquitoes reared in
      repellent-treated water were conditioned against oviposition site deterrence, as
      shown when choice tests were conducted 6 days post-emergence from the treated
      water. This demonstrates learning and memory in the mosquito Ae. aegypti, with
      implications for dengue vector surveillance and control.

PMID- 14651663
TI  - Reduced seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), human
      herpesvirus 8 (HHV8), related to suppression of Anopheles density in Italy.
AB  - In two formerly malarious parts of Italy, age-related seroprevalence rates of
      Kaposi's sarcoma-associated herpesvirus [human herpesvirus 8 (KSHV/HHV8)] were
      determined from local blood donors and correlated with periods of vector control
      during anti-malaria campaigns. In Veneto, decreased KSHV/HHV8 seroprevalence in
      the 1951-1955 birth cohort coincides with the peak of DDT house-spraying. In
      Sardinia, where larviciding augmented indoor DDT-spraying, a significant drop of
      KSHV/HHV8 seroprevalence between 1945 and 1950 and 1951-1955 birth cohorts (P =
      0.0046) coincides with suppression of the malaria vector Anopheles labranchiae
      Falleroni (Diptera: Culicidae). These results are consistent with age-related
      association between KSHV/HHV8 seroprevalence rates in native/resident populations
      and the density of malaria vectors in Veneto and Sardinia. This example supports
      our 'promoter arthropod' hypothesis on the role of haematophagous insects
      [putatively blackflies (Simuliidae), sandflies (Phlebotominae) and biting midges
      (Ceratopogonidae), as well as mosquitoes] when their bites induce
      hypersensitivity and immunosuppression, potentiate KSHV/HHV8 transmission via
      human saliva (when insect bite lesions are licked by another person whose saliva
      carries the virus) and may facilitate Kaposi's sarcoma.

PMID- 14651664
TI  - Blood pressure - lower targets, greater challenges.

PMID- 14651665
TI  - Physicians' prescribing attitudes to combined therapy with statins and fibrates.
AB  - OBJECTIVE: To assess the impact of a package insert revision and a drug-drug
      interaction warning embedded in a computerized prescription ordering system, on
      physicians' prescribing of concomitant statins and fibrates. METHODS: Data were
      obtained using a computerized prescription order entry system before and after
      administrative intervention advising of potentially adverse effects of this
      combined therapy. The number of prescriptions for statins and fibrates were
      counted monthly from January 1998 to June 2002 at the National Cardiovascular
      Center (NCVC). Counting was based on information from a prescription database
      file compiled from a computerized order entry system. The total number of
      prescriptions and frequency of requests for statins and fibrates were compared
      with the timing of either package insert revision or introduction of the warning
      on a computerized prescription ordering system. In addition, laboratory testing
      of renal function using serum creatinine (Scr) assays in patients treated with
      combined statins and fibrates was obtained from medical records at two stages
      during the study period (stage 1, January 1998 to June 1998; stage 2, January
      2002 to June 2002). RESULTS: There were 204 prescriptions for concomitant statins
      and fibrates at the beginning and 50 prescriptions at end of the study period.
      The number of prescriptions began to decrease in the latter half of 1999 with the
      percentage of concomitant use of statins and fibrates showing an evident downward
      trend from January 2001. This acceleration in the downward trend coincided with
      the introduction of the computerized warning message. Scr levels were measured in
      43.8% of patients in stage 1 and in 48.3% of patients in stage 2 in the past
      month. The percentage of patients having Scr levels measured in the past 6 months
      was 85.3% in stage 1 and 84.5% in stage 2. There was no significant difference in
      the percentages of patients whose Scr levels had been measured between the two
      stages. CONCLUSION: Revision of package inserts concerning combined therapy of
      statins and fibrates led to physicians' prescribing fewer of these combinations.
      A warning message displayed on a computerized prescription order entry system
      accentuated this effect.

PMID- 14651666
TI  - Relationship between erythrocyte lithium concentration and renal concentrating
      capacity.
AB  - BACKGROUND: Studies investigating possible correlations between plasma lithium
      concentration, lithium treatment duration, and frequency of lithium
      administration, and lithium nephrotoxicity have yielded conflicting results.
      OBJECTIVES: Our main objective was to investigate whether there was any
      relationship between erythrocyte lithium concentration (ELC) and renal side
      effects. Another objective of our study was to identify a parameter, which could
      be estimated inexpensively, for assessing possible renal side-effects of lithium.
      METHOD: Seventy Iranian inpatients with bipolar disorder entered this case
      control study. Medications taken concurrently by the patients were recorded. A
      direct method of measuring ELC was used in this study. The cases were patients on
      lithium who had urine specific gravity (SG) of 1.006 or less after 8-10 h water
      deprivation at night and the controls consisted of patients on lithium with urine
      SG of 1.011 or more after this period. Blood urea nitrogen, serum creatinine,
      sodium and potassium and urine SG, sodium, and potassium were measured in all
      patients during this time. Renal indices were compared by using independent
      sample t-test at a significance level of a P-value of 0.05 or less. Non
      parametric Spearman's rank correlation test was used to investigate the
      relationship between clinical variables and the indices of renal function.
      RESULTS: Results revealed that in case group mean serum sodium concentrations
      were significantly higher (P = 0.008) and mean urine sodium and potassium were
      significantly lower than those of controls (P = 0.004 and 0.007 respectively). We
      found no statistically difference in lithium ratios between the two groups.
      However, ELCs were significantly higher in the cases (P = 0.026). There were no
      significant correlation between concomitant use of neuroleptics, benzodiazepines
      or carbamazepine and ELC or lithium renal side-effects. CONCLUSION: This study
      showed that ELC may reflect lithium renal side-effects better than plasma lithium
      level.

PMID- 14651667
TI  - Stability of extemporaneously prepared saquinavir formulations.
AB  - AIMS: The effects of pH and excipients on the stability of saquinavir in
      extemporaneously prepared suspensions were assessed. The stability of a developed
      extemporaneously prepared saquinavir suspension was then determined at 5 and 25
      degrees C over 30 days. METHOD: Extemporaneous saquinavir 2 mg/mL formulations
      were prepared from soft gelatin capsule (Fortovase). Four batches of the
      formulations were buffered at pHs 2, 4, 5 and 7, whereas the other five batches
      were prepared in Milli-Q water, 0.5% (w/v) citric acid, 0.1% (w/v) sodium
      ascorbate, 10% (v/v) syrup and in vehicle containing both 0.5% (w/v) citric acid
      and 0.1% (w/v) sodium ascorbate. The stability of these formulations was tested
      at 25 degrees C. A final formulation of saquinavir suspension (60 mg/mL)
      containing both 10% (v/v) syrup and 0.5% (w/v) citric acid was developed and
      tested for stability at 5 and 25 degrees C for up to 30 days using a stability
      indicating high-performance liquid chromatographic method. RESULTS: Saquinavir
      was most stable at pH 2-4. Formulations containing sodium ascorbate, citric acid
      and syrup or both citric acid and sodium ascorbate were significantly more stable
      than the control formulation (saquinavir 2 mg/mL in Milli-Q water). CONCLUSION:
      The pH for optimal stability of saquinavir was around 2-4. Besides pH adjustment,
      saquinavir could also be stabilized by adding anti-oxidants. The saquinavir 60
      mg/mL formulation prepared with about a pH of about 4 was stable at both 5 and 25
      degrees C for at least 30 days.

PMID- 14651668
TI  - Application of cutaneous microdialysis to evaluate metronidazole and its main
      metabolite concentrations in the skin after a single oral dose.
AB  - OBJECTIVE: To measure the concentration of metronidazole and its
      hydroxymetabolite in plasma and cutaneous microdialysates and to compare
      metronidazole penetration into cutaneous microdialysates against theoretical
      predicted penetration in a peripheral compartment. METHOD: A single oral dose of
      2 g of the parent drug was administered to 10 healthy male volunteers.
      Microdialysis probes with 2 kDa molecular weight cut-off were inserted
      intradermally and were perfused with Ringer solution up to 8 h after drug
      ingestion. Drug and metabolite concentrations were measured by high performance
      liquid chromatography. RESULTS: Mean maximum concentration in plasma, cutaneous
      microdialysates and theoretical peripheral compartment were 214 +/- 49, 151 +/-
      52 and 146 +/- 38 micromol/L, respectively, and were achieved after about 2.1 +/-
      0.8, 2.8 +/- 1.0 and 6.0 +/- 2.9 h. The extent of penetration into cutaneous
      microdialysates and theoretical peripheral compartment relative to plasma were
      0.672 +/- 0.196 and 0.675 +/-0.207, respectively, and did not differ
      significantly. Moreover, maximum concentration as well as area under
      concentration-time curve in these compartments also did not differ significantly.
      CONCLUSION: Use of cutaneous microdialysis technique permits the characterization
      of true systemic drug disposition, for optimizing drug treatment strategies.

PMID- 14651669
TI  - Stability of dopamine hydrochloride 0.5 mg/mL in polypropylene syringes.
AB  - OBJECTIVE: To determine the stability of dopamine hydrochloride diluted to 0.5
      mg/mL in isotonic glucose infusion and stored in 50 mL polypropylene syringes
      from two different suppliers. METHODS: Polypropylene syringes containing dopamine
      hydrochloride 0.5 mg/mL were stored protected from light at 25 degrees C/60%
      relative humidity for 1 week, at 4 degrees C/ambient humidity for 3 months and at
      -20 degrees C/ambient humidity for 6 months. Samples were periodically withdrawn
      and the concentration of dopamine hydrochloride determined using a stability
      indicating high-performance liquid chromatography method. The appearance of the
      solutions with respect to colour, clarity and precipitation was studied and the
      pH of the solutions measured. RESULTS: The concentration of dopamine
      hydrochloride in the solutions remained at least 95% of the initial concentration
      after storage at 25 degrees C for 1 week and at 4 degrees C for 3 months.
      Variation in dopamine concentration was observed in syringe samples, stored
      frozen, from two suppliers. The mean concentration was >/=95% for product stored
      in syringes from Codan and >/=90% of initial concentration when stored in
      syringes from Braun. In some of the syringes from Braun, the concentration was
      lower than 90%. The samples in all syringes had to be homogenized after thawing
      to give a uniform solution. There were no other evident changes in the physical
      appearance or pH of the solutions during the study. CONCLUSION: Dopamine
      hydrochloride 0.5 mg/mL in isotonic glucose solution is stable when protected
      from light for 1 week at 25 degrees C/60% relative humidity and for 3 months at 4
      degrees C/ambient humidity in Codan and Braun syringes. The cause of content
      variability observed in solutions stored frozen in Braun syringes needs further
      investigation. Braun syringes should not be used if the product is to be frozen.
      The stability of the frozen product, in Codan syringes is 6 months.

PMID- 14651670
TI  - Selecting outcome parameters in studies aimed at improving rational use of
      antibiotics - practical considerations.
AB  - When designing studies of the optimal use of antimicrobial drugs, it is important
      to define at an early stage, which outcome parameters to use. It must be clear to
      which category a parameter to be measured belongs: the structure, the process or
      a clinical outcome. Attention must be paid to the measurement scales as well as
      the statistical tests to be used. The outcome measure must be sensitive, specific
      and reliable. Furthermore, the timeframe chosen for the performance of a study
      should be validated. Whether process parameters or clinical outcomes are to be
      preferred depends on the settings and the intended purpose. The essential point
      is the appropriate choice of outcome measure for the study. Examples drawn from
      the field of quality of use of antimicrobial drugs are discussed.

PMID- 14651671
TI  - Aminoglycoside and vancomycin serum concentration monitoring and mortality due to
      neonatal sepsis in Saudi Arabia.
AB  - OBJECTIVE: To assess the effectiveness of monitoring of serum concentration of
      aminoglycosides in neonates. METHOD: A retrospective evaluation of serum
      concentration monitoring of aminoglycosides (gentamicin and amikacin) and
      vancomycin in neonates treated for sepsis in a maternity and children hospital in
      Jeddah, Saudi Arabia, over the period 1998-2000. RESULTS: The total number of
      requests for monitoring increased sixfold in 1999 and 12-fold in 2000 relative to
      1998. For aminoglycosides, the incidence of both subtherapeutic peak and toxic
      trough serum levels decreased significantly (P < 0.05) in 1999 and 2000 compared
      with 1998. Furthermore, the rate of neonatal mortality caused by sepsis showed
      reduction in both 1999 (34%) and 2000 (35%) in comparison with 1998 (45%).
      Vancomycin trough (effective) concentration monitoring revealed no change in the
      incidence (30%) of levels at subtherapeutic values (<5.0 microg/mL) between the
      compared years. Furthermore, the rate of toxic levels (>10 microg/mL) increased
      in both 1999 (31%) and 2000 (39%) relative to 1998 (25%). CONCLUSION: Therapeutic
      drug monitoring of vancomycin needs re-evaluation in the hospital to explain why
      existing methods are ineffective.

PMID- 14651672
TI  - Managing insomnia in the elderly - what prevents us using non-drug options?
AB  - OBJECTIVE: To identify strategies needed to increase use of non-drug
      interventions in the management of insomnia in the elderly. METHODS: A
      questionnaire was mailed to 425 general practitioners (GPs) in the South
      Australian Southern Division of General Practice. To provide a consumer
      perspective, 16 older persons attended focus groups. RESULTS: Responses from 209
      GPs showed the role of non-drug strategies in insomnia management was widely
      known, however access to and the usefulness of these strategies was less well
      known. GPs' perceptions of patients' expectations regarding medication were the
      greatest barrier. Patient inquiries about other options, patients' willingness to
      consider alternatives, printed information for patients on non-drug options, and
      step-by-step procedures to follow during consultations were considered enabling
      factors. Most consumers reported problems with sleeping but thought the GP could
      not help them with their sleep problems. In contrast to GPs' perceptions,
      consumers expressed interest in alternative treatments and willingness to
      participate in education sessions. CONCLUSIONS: Strategies to increase the use of
      non-drug alternatives need to provide GPs with information on access to, and the
      usefulness of, non-drug strategies. Consumers need concurrent education to inform
      them that GPs can help manage insomnia, and that they need to express willingness
      to trial non-drug strategies. Effective communication between GPs and consumers
      is paramount.

PMID- 14651673
TI  - Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation
      in human microsomes.
AB  - BACKGROUND AND OBJECTIVES: Trimethadione (TMO), an antiepileptic drug, may be
      used as a candidate for estimating hepatic drug-oxidizing activity. While TMO
      metabolism is mainly catalysed by CYP2C9, CYP2E1 and CYP3A4 the contribution of
      the different isoforms is unclear. In this study, we determined the percentage
      contribution of the three CYPs (CYP2C9, CYP2E1 and CYP3A4) to TMO N
      demethylation. METHOD: We used human liver microsomes and human recombinant CYPs
      expressed in human B-lymphoblast cells and baculovirus-infected insect cells.
      RESULTS: The mean Km, Vmax and Vmax/Km values of TMO N-demethylation in human
      microsomes were 3.66 (mm), 503 (pmol/min/mg) and 2.61 (mL/h/mg), respectively. In
      the microsomes from human B-lymphoblast cells or baculovirus-infected insect
      cells, CYP 2C9, CYP 2E1 and CYP3A4 exhibited similar Km and higher Vmax in
      baculovirus-infected insect cells than B-lymphoblast cells. In baculovirus
      infected insect cells, CYP2C9, CYP2E1 and CYP3A4 exhibited activities of 32, 286
      and 77 pmol/min/pmol CYP, respectively. No CYP activity catalysed by CYP1A2 and
      2D6 were detected in the two human cDNA expressed CYP isoforms. CONCLUSION: TMO
      is metabolized not only by CYP2E1 but also CYP3A4 and CYP2C9. The order of this
      metabolism is as follows: CYP2E1 >> CYP3A4 > CYP2C9.

PMID- 14651674
TI  - Pharmacoepidemiologic investigation of a clonazepam-valproic acid interaction by
      mixed effect modeling using routine clinical pharmacokinetic data in Japanese
      patients.
AB  - Non-linear Mixed Effects Modeling (NONMEM) was used to estimate the effects of
      clonazepam-valproic acid interaction on clearance values using 576 serum levels
      collected from 317 pediatric and adult epileptic patients (age range, 0.3-32.6
      years) during their clinical routine care. Patients received the administration
      of clonazepam and/or valproic acid. The final model describing clonazepam
      clearance was CL = 144.0 TBW-0.172 1.14VPA, where CL is total body clearance
      (mL/kg/h); TBW is total body weight (kg); VPA = 1 for concomitant administration
      of valproic acid and VPA = zero otherwise. The final model describing valproic
      acid clearance was CL (mL/kg/h) = 17.2 TBW-0.264 DOSE0.159 0.821CZP 0.896GEN,
      where DOSE is the daily dose of valproic acid (mg/kg/day); CZP = 1 for
      concomitant administration of clonazepam and CZP = zero otherwise; GEN = 1 for
      female and GEN = zero otherwise. Concomitant administration of clonazepam and
      valproic acid resulted in a 14% increase in clonazepam clearance, and a 17.9%
      decrease in valproic acid clearance.

PMID- 14651675
TI  - Delayed adverse reactions to iodinated radiographic contrast media after coronary
      angiography: a search for possible risk factors.
AB  - OBJECTIVE: The incidence of and risk factors for delayed adverse events (DAEs)
      that appear from 1 h to 7 days after injection of radiographic contrast media
      were investigated in patients who had undergone coronary angiography (CAG).
      METHODS: DAEs were monitored by questionnaire in 155 patients who received
      iomeprol. Isosorbide dinitrate was injected in every case. Risk factors for DAEs
      were analysed by a logistic regression model. RESULTS: Of 118 patients who
      returned questionnaires, 54 complained of DAEs, although no severe or fatal
      reactions occurred. Erythema, rash and nausea were frequent events. Female
      gender, total dose of isosorbide dinitrate <2 mg, and execution of acetylcholine
      provocation test were found to be the major risk factors, and the incidence of
      DAEs increased as the number of risk factors increased. CONCLUSION: Care should
      be taken when CAG is performed on female patients who undergo acetylcholine
      provocation tests and receive low-dose nitric oxide donor injections.

PMID- 14651676
TI  - Use of health-related quality of life in prescribing research. Part 1: why
      evaluate health-related quality of life?
AB  - Clinicians, regulatory authorities, and pharmaceutical companies increasingly
      recognize the importance of assessing the patient's perspective on the impact of
      disease and its treatment on their health-related quality of life (HRQoL). This
      article describes the importance of assessing HRQoL, particularly in patients
      with chronic disease, provides examples of the different types of instrument
      available for measuring HRQoL and considers how such assessment can aid medical
      decision making. In addition we consider the potential role of HRQoL assessment
      in routine clinical practice, and its use in licensing and health technology
      appraisal.

PMID- 14651678
TI  - Nurse-managed clinics: issues in evaluation.
AB  - BACKGROUND: Nurse-managed clinics (NMCs) have been in existence for over 30
      years. Evaluation of such clinics has been sparse and most have used entirely
      quantitative techniques. This article explores the importance of evaluation of
      NMCs using the Mana Health Clinic in Auckland, New Zealand as an example.
      DISCUSSION: Fourth generation evaluation is offered as an appropriate methodology
      for undertaking evaluation of NMCs. Fourth generation evaluation actively seeks
      involvement of clients in the process and outcome of the evaluation, resulting in
      participation and empowerment of stakeholders in the service - a precept often
      forgotten in traditional evaluation strategies and of vital importance in
      understanding why people use NMCs. The method proposed here also incorporates the
      need for quantitative data. CONCLUSION: The main argument proposed here is that a
      combination of qualitative and quantitative data sources is likely to give the
      greatest understanding of NMCs utilization. Evaluation of NMCs is vital to the
      continuation of this type of health service. However, evaluation must be
      appropriate to the service being studied. Fourth generation evaluation used to
      elicit client's perceptions of the clinic along with quantitative data is offered
      as an appropriate means of achieving this.

PMID- 14651679
TI  - Management of chronic illness: voices of rural women.
AB  - BACKGROUND: The prevalence and cost of chronic illness globally and in the United
      States of America continue to escalate and the day-to-day management of these
      conditions presents a major challenge. The burden of chronic illness
      disproportionately affects vulnerable populations such as women and those living
      in rural areas. AIM: To add to the knowledge base of illness management by
      chronically ill rural women through examining their individual perceptions of the
      illness experience. METHOD: The Women to Women project provided a nursing
      research-based computer intervention model for conducting support groups,
      providing health education, and fostering self-care, via personal computers and
      evaluated its effect on the women's psychosocial health. FINDINGS: Fatigue and
      pain were the major physical symptoms that impacted the women's quality of life,
      with depression and stress being the primary emotions they experienced. The
      characteristics of humour, hope, and courage were key in their successful
      adaptation to living with chronic illness. CONCLUSIONS: The women's voices relate
      how they manage their illness responses and adaptation mechanisms. The data
      provide nurses with information to heighten their sensitivity to clients' day-to
      day needs and experiences. It will assist them in their designing and planning of
      interventions that will enable clients to adapt and to have the best quality of
      life possible within the limitations of their chronic illnesses. The data are
      also important to nurses involved in rural research and theory development
      concerning self-management and adaptation to chronic illnesses.

PMID- 14651680
TI  - Hysterectomy: a case study of one woman's experience.
AB  - BACKGROUND: There are many published qualitative studies in the large volume of
      literature about hysterectomy documenting themes common to the majority of
      participants, such as social support, feelings of illness and wellness, pain and
      resumption of normal life rather than events which were unique or exceptional.
      AIM: This study explores the meaning of the experience of abdominal hysterectomy
      for one woman. METHODS: Single client case study method was used. An overview of
      case study is presented and the rationale for its selection as an appropriate
      methodology for this study given. The participant and her "significant others"
      are introduced. FINDINGS: Four major themes relating to the participant's
      experience were identified: doubts and justifications, pain, embodiment and sense
      of betterness. These are discussed in relation to the participant, the research
      literature and nursing and medical practice. CONCLUSION: Highlighting the case of
      one woman and analysing her experience as a single case study has produced a
      depth of material not previously available in other studies. The findings should
      be of use to staff working in gynaecological nursing, but could also be used in
      the education of nursing and midwifery students.

PMID- 14651681
TI  - Nursing home staff attitudes towards residents with dementia: strain and
      satisfaction with work.
AB  - BACKGROUND: Occupational and resident characteristics affect levels of staff
      stress and satisfaction in nursing homes, and levels of staff turnover are high.
      Working with more cognitively impaired residents, especially on day shift, is
      associated with high levels of stress in nursing home staff. Workload is highly
      predictive of the experience of burden and job pressure, while these outcomes
      vary according to whether staff work full- or part-time. AIMS: To investigate the
      attitudes of nursing home staff towards residents, strain related to dementia
      care and satisfaction with work and their associations with demographic,
      occupational and behavioural disturbance in the home. METHODS: A cross-sectional
      design was adopted, using a self-completion questionnaire survey of 253 nursing
      home staff from 12 nursing homes in Sydney's eastern suburbs, and behavioural
      assessment of all 647 residents from 11 of the 12 homes. Staff attitudes and
      strain were measured using the Swedish Strain in Nursing Care Assessment Scale
      and satisfaction using the Swedish Satisfaction with Nursing Care and Work
      Assessment Scale. RESULTS: Staff members' five most prevalent perceptions of
      residents with dementia were that they are anxious, have little control over
      their difficult behaviour, are unpredictable, lonely and frightened/vulnerable.
      The five attributes staff found most difficult to cope with were being
      aggressive/hostile, having little control over their difficult behaviour, being
      stubborn/resistive, deliberately difficult, and unpredictable. Although 91% of
      staff reported that they were happy in their job, a quarter reported that
      residents provided no job satisfaction. The five satisfaction statements most
      agreed with were "The patients/residents at work nearly always receive good
      care", "It is important to try and enter into the way patients experience what
      happens to them", "Relatives are given enough information about care and
      treatment", "I enjoy my current work situation" and "Our work organisation is
      good". There were significant differences between homes in levels of strain
      related to dementia care that were not accounted for by the level of behavioural
      disturbance. CONCLUSIONS: Nursing home staff tended to perceive residents in more
      negative than positive ways. Staff were generally satisfied with their work.
      Factors other than resident behavioural disturbance are important influences in
      nursing staff strain.

PMID- 14651682
TI  - Classifying general and specialist children's nursing competencies.
AB  - BACKGROUND: Whilst there is evidence in the literature to support the
      continuation of a children's nursing qualification, the distinction between
      generalist and specialist nursing is insufficiently comprehensive to distinguish
      children's nursing from other branches of nursing. AIM: To develop a definition
      of children's nursing and specialist children's nursing in terms of competencies
      as the basis for differentiating them from other forms of nursing. DESIGN: A
      multi-method comparative design incorporating a case study approach was used.
      This included a nominal group technique, focus groups, Delphi survey and semi
      structured interviews. Two arms of data collection were undertaken concurrently
      (during 1998-2000) with children's nurses (n = 146) and specialist children's
      nurses (children's cancer nurses, n = 37) from a number of centres in the United
      Kingdom (UK). FINDINGS: The holistic competencies developed from the data exposed
      characteristics of knowledge, skills, abilities, values and qualities displayed
      in the context of professional work for both groups of nurses. A classification
      of competencies was developed inductively from the data by two independent
      researchers through the labelling, defining and ordering of competencies. The
      resulting hierarchy of competencies and sub-competencies illustrates
      relationships between children's nurses and specialist children's nurses and
      provides a detailed definition of children's nursing and specialist children's
      nursing. CONCLUSION: There is a significant common element in these two areas of
      nursing practice, and generalist preparation in children's nursing is the
      foundation of specialist children's nursing practice. Generalist knowledge and
      skills are expanded in specialist practice and there is also evidence of
      specialist practice that is beyond the scope of general nursing practice.

PMID- 14651683
TI  - Evaluating a management of aggression unit for student nurses.
AB  - BACKGROUND: Workplace violence is acknowledged as a major problem in health care
      settings and affects staff morale, recruitment, retention and direct health care
      budgets. Staff training is advocated as the appropriate managerial response, but
      identifying appropriate training and trainers is difficult and there is little
      published evidence of training effectiveness. Student nurses are frequent targets
      of aggression but are less likely to receive specific training. AIMS: The study
      considered the application of a model of learning to a 3-day learning unit for
      diploma-level student nurses on the "prevention and management of aggression". It
      aimed to measure student outcomes of the unit and gain information about more
      general issues in evaluating training effectiveness. METHODS: A repeated measures
      longitudinal design was used to obtain data from three cohorts of student nurses
      (3 x 80 approximately) at four time points over an 8-month period. A
      questionnaire was administered twice before the unit, at its conclusion and
      approximately 3 months afterwards, following two clinical placements. RESULTS:
      Statistically significant changes were demonstrated in a number of areas,
      including number of risk factors identified, and five "factors" identified from
      the questionnaire statements. STUDY LIMITATIONS: The results refer to one course
      for student nurses that had many common elements with popular training courses
      for qualified staff, including inter-personal and breakaway skills. However,
      restraint skills were not included. CONCLUSIONS: It is possible to provide
      training that produces desirable, statistically demonstrable and durable change
      in knowledge, behaviour, attitudes and confidence using a rigorous longitudinal
      evaluation research design.

PMID- 14651684
TI  - Educating for rural nursing practice.
AB  - BACKGROUND: Rural hospitals in Australia, as in many countries, face challenges
      in ensuring that appropriate, quality services are provided. AIMS: The overall
      aim of this study was to explore the issues that impact on the ability of rural
      hospitals to provide effective health care. METHODS: We used a qualitative
      descriptive method and purposive sampling, and conducted interviews in hospitals
      in rural Victoria, Australia. The data collected enabled major issues that impact
      on hospital service delivery to be identified. Using thematic analysis, global
      themes were extracted and organized around a thematic network. FINDINGS: The
      workforce was an important theme. Whilst the impact of medical shortages on
      hospital function has been considered in other studies, little consideration has
      been given to the rural nursing workforce. The need to maintain an appropriately
      educated rural nursing workforce emerged as one of the major issues that impact
      on rural hospital service delivery. In Australia, there has been a great deal of
      discussion about the educational preparation required for rural nursing practice,
      with the emphasis on postgraduate study. However, the majority of rural nurses do
      not have postgraduate qualifications and face significant barriers in obtaining
      them. Although the vast majority of literature claims that postgraduate
      preparation is vital for rural nursing practice, this research suggests that the
      future rural nursing workforce will be recruited from undergraduate courses in
      regional universities. However, there is a need to include specific theoretical
      and operational preparation in undergraduate education, to enable nurses to make
      the transition to rural practice more readily. CONCLUSIONS: Rural nurses are
      central to the delivery of health services in rural hospitals. Future rural
      nursing recruitment and retention hinges on ensuring that they have the
      confidence, knowledge and skills to deliver safe, appropriate and effective care.

PMID- 14651685
TI  - Central venous catheter dressings: a systematic review.
AB  - BACKGROUND: Gauze and tape or transparent polyurethane film dressings such as
      Tegaderm, Opsite or Opsite IV3000 are the most common types of dressing used to
      secure central venous catheters (CVCs). Currently, there are no clear guidelines
      as to which type of dressing is the most appropriate. AIMS: To identify whether
      there are any differences between gauze and tape and/or transparent polyurethane
      film dressings in the incidence of CVC-related infection, catheter-related
      sepsis, catheter security, tolerance to dressing material, dressing condition and
      ease of application in hospitalized patients. METHODS: The Cochrane Controlled
      Trials Register and Medline, Embase and CancerLit databases were searched to
      identify any controlled trials comparing the effects of gauze and tape and/or
      transparent polyurethane dressings on CVCs. Additional references were sought
      from published and non-published literature. Twenty-three studies were reviewed.
      Data were extracted independently from each paper by two members of the review
      team and results compared. Differences were resolved either by consensus or
      referral to a third person. Authors were contacted for missing information.
      RESULTS: Of the 23 studies reviewed, 15 were excluded. Of the remaining eight,
      data were available for meta-analysis from six studies. Of the six included
      studies, two compared gauze and tape with Opsite IV3000, two compared Opsite with
      Opsite IV3000, one compared Tegaderm with Opsite IV3000, and one compared
      Tegaderm with Opsite. CONCLUSIONS: There was no evidence of any difference in the
      incidence of infectious complications between any of the dressing types compared
      in this review. Each of these comparisons was based on no more than two studies
      and all of these studies reported data from a small patient sample. Therefore it
      is unlikely that any of these comparisons would have had sufficient power to
      detect any differences between groups.

PMID- 14651686
TI  - Workplace stress in nursing: a literature review.
AB  - BACKGROUND: Stress perception is highly subjective, and so the complexity of
      nursing practice may result in variation between nurses in their identification
      of sources of stress, especially when the workplace and roles of nurses are
      changing, as is currently occurring in the United Kingdom health service. This
      could have implications for measures being introduced to address problems of
      stress in nursing. AIMS: To identify nurses' perceptions of workplace stress,
      consider the potential effectiveness of initiatives to reduce distress, and
      identify directions for future research. METHOD: A literature search from January
      1985 to April 2003 was conducted using the key words nursing, stress, distress,
      stress management, job satisfaction, staff turnover and coping to identify
      research on sources of stress in adult and child care nursing. Recent (post-1997)
      United Kingdom Department of Health documents and literature about the views of
      practitioners was also consulted. FINDINGS: Workload, leadership/management
      style, professional conflict and emotional cost of caring have been the main
      sources of distress for nurses for many years, but there is disagreement as to
      the magnitude of their impact. Lack of reward and shiftworking may also now be
      displacing some of the other issues in order of ranking. Organizational
      interventions are targeted at most but not all of these sources, and their
      effectiveness is likely to be limited, at least in the short to medium term.
      Individuals must be supported better, but this is hindered by lack of
      understanding of how sources of stress vary between different practice areas,
      lack of predictive power of assessment tools, and a lack of understanding of how
      personal and workplace factors interact. CONCLUSIONS: Stress intervention
      measures should focus on stress prevention for individuals as well as tackling
      organizational issues. Achieving this will require further comparative studies,
      and new tools to evaluate the intensity of individual distress.

PMID- 14651687
TI  - The effects of extended workdays on fatigue, health, performance and satisfaction
      in nursing.
AB  - BACKGROUND: Several authors have claimed that 12-hour shifts in nursing are
      better for both employees and patient care. However, although the research has
      found positive effects on satisfaction with working hours and free time, the
      effects on employee fatigue, health and performance have mostly been neutral or
      negative. AIM: Work schedules should preferably be beneficial for satisfaction,
      fatigue, health and performance. This study therefore investigated whether shifts
      that are extended only slightly can combine the positive effects of the 12-hour
      shift with the positive effects of the 8-hour shift. The study investigated the
      effects of 9-hour shifts. METHOD: A total of 134 nurses from three nursing homes
      in the Netherlands completed a questionnaire on fatigue, health, performance and
      satisfaction. One group worked 8-hour shifts, and the other worked 9-hour shifts.
      RESULTS: Nurses who worked 9-hour shifts were on average more fatigued, had more
      health complaints, and were less satisfied with their working hours and free time
      than those who worked 8-hour shifts. Their performance was slightly poorer. About
      70% to 80% of the 8- and 9-hour nurses preferred to work a maximum of 8 hours
      during morning/early and afternoon/late shifts. CONCLUSIONS: The 9-hour shift
      seemed to combine the negative aspects of the 12-hour shift with the negative
      aspects of the 8-hour shift. It is suggested that the 9-hour shift had more
      negative effects than the 12-hour shift because: (1) nurses could not choose what
      shift length they worked; (2) many worked part-time; and (3) they already had
      many days off. It is also suggested that increases in workload since the 1980s
      make current extended shifts in nursing more fatiguing.

PMID- 14651691
TI  - Liberating our conceptualization of 'evidence'.

PMID- 14651688
TI  - Response to: Buchan J.E.F., Corner J. & Bond S. (2003) JAN Forum. Journal of
      Advanced Nursing 43, 531-534.

PMID- 14651693
TI  - Research into patients' perspectives: relevance and usefulness of
      phenomenological sociology.
AB  - BACKGROUND: The dominant epistemology underpinning much inquiry in the field of
      patient evaluation of health care is positivist, with categorization and
      quantification being high priorities, despite the highly personal and dynamic
      nature of people's responses to their health care experiences. The mis-match
      between underpinning theoretical assumptions and the nature of the subject under
      investigation has led to ineffectiveness in much current inquiry into patients'
      perspectives. More needs to be learnt about patients' processes of evaluation
      prior to any summary assessment of the quality of their care. AIMS: This paper
      documents the search for a close fit between a study's research questions and a
      theoretical perspective with which to underpin the research. It describes the
      benefits of identifying a specifically relevant perspective, in this case
      phenomenological sociology, and discusses the potential of that particular
      perspective to underpin research within health care. METHODS: Research questions
      relating to patients' processes of evaluation were established. The possible
      contribution of a range of interpretative methodologies was considered. While all
      were relevant to some degree, phenomenological sociology was identified as having
      considerable specific potential to illuminate the patient's process of
      evaluation. FINDINGS: The particular strengths of phenomenological sociology
      relevant to the investigation of patients' processes of reflection are in
      highlighting the importance of subjectivity; its insistence on a clear link from
      theoretical development right back to the raw data; its wealth of evocative ideas
      and concepts that support the investigation of the development of interpretation;
      and the relatively accessible language and style of its texts. CONCLUSION: Time
      spent evaluating the potential contribution of different theoretical perspectives
      to a study is worthwhile, as a good choice can not only support but also enhance
      the quality of the research. Phenomenological sociology has much potential to
      underpin research into patient evaluation of health care and in nursing research
      more widely.

PMID- 14651694
TI  - Psychometric properties of the SF-36 in the early post-stroke phase.
AB  - BACKGROUND: Patients who have had a stroke are a large group in whom long-term
      disability is common and therefore impaired general health is likely. The Short
      Form 36 (SF-36) is a popular measure of general health that has been used with
      this patient group, but not all aspects of its psychometric properties have been
      established for use in this context, and its use in the early post-stroke phase
      has been neglected. AIMS: To examine the reliability, validity and sensitivity to
      change of the SF-36 (UK version I) in patients in the early post-stroke period.
      DESIGN: A prospective, observational study of stroke outcomes was carried out.
      RESEARCH METHODS: From May 1996 to April 1997, patients who had had a stroke were
      identified by 24 general practices in Scotland and were recruited within 1 month
      of their stroke, whether in hospital or at home. Outcome measures including the
      SF-36 were administered at one, 3 and 6 months after onset. RESULTS: The internal
      consistency of the eight subscales at all three time-points was good except for 1
      month Vitality (alpha = 0.6824) and 3 month General Health (alpha = 0.6650),
      which were borderline in comparison with the criterion value of 0.7. Construct
      validity was adequate overall, although correlations between Role Physical and
      General Health and the Barthel Index and Canadian Neurological Scale were lower
      than hypothesized. Most SF-36 subscales were sensitive to change between 1 and 3
      months post-stroke, but none detected change between 3 and 6 months. CONCLUSIONS:
      There were some practical problems in using the SF-36 in an acutely unwell stroke
      population. However, analysis of psychometric properties suggested that most of
      the subscales were adequately reliable and valid. Sensitivity to change was
      poorer in the later stages of the study.

PMID- 14651695
TI  - Efficacy of swallowing training for residents following stroke.
AB  - BACKGROUND: The presence of dysphagia is associated with an increased risk of
      mortality, malnutrition, dehydration, compromised pulmonary function, and
      disability. Appropriate swallowing training can establish optimal nutritional
      status and eliminate or reduce the risk of developing medical complications
      associated with swallowing impairment. AIM(S) OF THE STUDY: The aim of this study
      was to examine the functional swallowing and nutritional outcomes of swallowing
      training in institutionalized stroke residents with dysphagia. DESIGN AND
      METHODS: A quasi-experimental parallel cluster design was used. Seven
      institutions with similar bed sizes were selected. All subjects in the
      experimental group received a structured swallowing training programme. The
      subjects in the experimental group (n = 40) received 30 minutes of swallowing
      training each day for 6 days per week for 8 weeks. The control group (n = 21) did
      not receive any training. RESULTS: After swallowing training, mean differences in
      volume per second, volume per swallow, mid-arm circumference and body weight
      between pre- and post-training of the experimental group were significantly
      higher than for the control group, while mean differences in neurological
      examination and choking frequency during meals for the experimental group were
      significantly lower than in the control group. CONCLUSION: This study used
      objective timed swallowing tests, a swallowing questionnaire, and a neurological
      examination to evaluate the effects of swallowing training. However,
      videofluroscopy is generally considered the best method for evaluating the
      pharyngeal and esophageal stages of swallowing, and introducing this technique is
      recommended for future studies. Furthermore, it is recommended that nursing
      professionals should conduct swallowing training protocols in stroke patients to
      help prevent aspiration from dysphagia.

PMID- 14651696
TI  - Management of childhood constipation: parents' experiences.
AB  - BACKGROUND: Constipation in childhood is common and places a burden on child
      health services. Whilst constipation can have a variety of causes, for most
      children it is usually non-organic and requires limited intervention. It has been
      suggested that health professionals can resent consultations for such a common
      problem, believing them to be inappropriate. However, they can underestimate the
      impact of this condition, leading to adverse clinical effects, as well as
      parental dissatisfaction. Little research has explored parents' experiences of
      consulting health professionals about the management of childhood constipation.
      AIM: To explore parents' experiences of consulting health professionals about
      management of childhood constipation and to use the findings to inform more
      effective therapeutic encounters when responding to parental concerns. METHODS: A
      phenomenological approach was adopted, using in-depth interviews with parents of
      14 children receiving health interventions for constipation. FINDINGS: Six themes
      emerged from analysis including: 'enduring and extreme constipation', which
      reflected the substantial and sustained impact of the child's constipation;
      'dismissed and fobbed off', which captured parents' feelings that their concerns
      were frequently dismissed by health professionals; 'asserting the need for
      action', a perception that they had reached a point at which they had to demand
      some intervention; and 'validation and acknowledgement', which reflected
      acknowledgment that, finally, their concerns for their child had been taken
      seriously and acted on. DISCUSSION: The findings indicate a failure by some
      health professionals to appreciate fully the significance of childhood
      constipation, thereby appearing to be unconcerned and insensitive to the needs of
      child and family. The impact of this is a potential loss of trust in health
      professionals by parents, which can then have implications for how they perceive
      and access health services for management of this common childhood problem. The
      findings offer an insight into parental experiences and indicate the need for a
      more sensitive approach during health consultations.

PMID- 14651697
TI  - Educational needs of families caring for Chinese patients with schizophrenia.
AB  - BACKGROUND: Schizophrenia is a disruptive and distressing illness for patients
      and family members who care for them. As in Western countries more than 20% of
      people with schizophrenia in Hong Kong are discharged to their homes, but their
      families are unprepared to care for them. Studies of caregivers' opinions about
      the information required to supervise patients are limited, particularly for the
      purposes of optimizing family-centred care. AIM: The aim of this study was to
      identify the educational needs of Chinese families caring for a relative with
      schizophrenia. METHODS: A cross-sectional survey was conducted in Hong Kong with
      a random sample of 204 family members caring for a relative with schizophrenia. A
      Chinese version of the Modified Educational Needs Questionnaire, validated in a
      previous study, was used to identify educational needs that family caregivers
      considered important in caring for mentally ill relatives. FINDINGS: Educational
      needs perceived as important by caregivers included gaining information about
      early warning signs of illness and relapse, effects of medication and ways of
      coping with patients' bizarre and assaulting behaviour. Gender, education level
      and closeness of the relationship with the patient correlated positively and
      significantly with need importance. Conversely, the relationship between duration
      of caring for patient and need importance correlated significantly but
      negatively, indicating the adverse effect of enduring mental illness on family
      caregivers' interest in mental health education. CONCLUSION: This study
      emphasizes the importance of assessing specific family needs in caring for a
      relative with mental illness. It also raises concern about the negative effects
      of the length of time of caring for such patients and the role of socio-economic
      factors on the perceived educational needs of these families.

PMID- 14651698
TI  - Korean mothers' psychosocial adjustment to their children's cancer.
AB  - BACKGROUND: During the course of adjustment to their child's illness and medical
      treatment, parents of children with cancer may experience numerous challenges and
      difficulties. Although parental adjustment has been a research topic for many
      years, little research has been conducted among families in different cultures
      and countries. AIM: To identify factors that influence maternal psychosocial
      adjustment to childhood cancer using a new cultural group: Korean. METHODS: A
      sample of 200 Korean mothers of children with cancer was included in the study.
      Guided by the double ABCX model of family adjustment and adaptation, a series of
      variables (i.e. maternal stress, coping, social support and selected illness
      related and demographic questions) were examined for their relationships with
      maternal psychosocial adjustment to childhood cancer. RESULTS: Using a
      hierarchical multiple regression, we found perceived level of stress, coping,
      social support, and time since diagnosis to be significant correlates of maternal
      psychosocial adjustment. Stress accounted for most (50%) of the total variance
      explained (56%) in maternal adjustment. CONCLUSION: The results suggest that the
      stress-coping framework may be appropriate in explaining maternal responses to
      childhood cancer across cultures.

PMID- 14651699
TI  - Nursing needs of acutely ill older people.
AB  - BACKGROUND: Investigating older acutely ill hospitalized patients' nursing needs
      and quality of care is paramount, given the growing pressure on nurses to provide
      increasingly intensive levels of care to a growing older population while at the
      same time working with reduced staffing levels. AIMS: The aims of this study were
      to determine: (1) important aspects of nursing care as perceived by older
      patients, their family member/carer who observed care during hospitalization, and
      nurses; (2) satisfaction levels of patients, family/carers and nurses on nursing
      care received; and (3) mismatches between nursing care priorities and
      satisfaction with nursing care. METHODS: Two hundred and thirty-two acutely ill
      patients aged over 65 years, 99 carers/family members and 90 nurses completed the
      Caregiving Activities Survey, which measures importance of and satisfaction with
      various aspects of nursing care. Qualitative data, which qualified responses to
      survey items, were also obtained from participants. RESULTS: Patients, carers and
      nurses perceived that carrying out doctors' orders was the most important aspect
      of nursing care, followed by physical care, psychosocial care and discharge
      planning. Nurses and carers rated physical care, psychosocial care and discharge
      planning more highly than patients. Physical care was rated highly by patients in
      terms of importance, but rated moderately in terms of satisfaction. Carers' and
      patients' ratings of satisfaction with physical care were lower than nurses'
      ratings of opportunities to provide it. The importance of discharge planning was
      rated highly by nurses but all groups were only moderately satisfied with this
      aspect of care. STUDY LIMITATIONS: The findings do not apply to acutely ill older
      patients with confusion, mental illness or more than early stage dementia.
      CONCLUSIONS: Patients, nurses and family/carers were generally in agreement about
      the relative importance of particular aspects of nursing care. Nurses may need to
      communicate more effectively with older patients and their family carers about
      the particular roles they will play during the patient's hospital episode, the
      expectations they have of patients in the process of healing and recovery, and
      the reasons for the actions they take in aiding this process. The findings are
      useful in making nurses more aware of the expectations and needs of older
      hospital patients and their carers. They provide evidence for developing both new
      models of nursing care for this patient group, and nursing education programmes.

PMID- 14651700
TI  - Effect of music on chronic osteoarthritis pain in older people.
AB  - BACKGROUND: Osteoarthritis is the most common degenerative disease in humans. It
      usually begins in middle age and is progressive. Chronic pain in older people
      presents a significant obstacle in maintaining function and independence.
      Previous studies have shown that music can improve motivation, elevate mood, and
      increase feelings of control in older people. PURPOSE: The purpose of this
      randomized clinical trial was to examine the influence of music as a nursing
      intervention on osteoarthritis pain in elders. METHOD: Data were collected using
      the short form of the McGill Pain Questionnaire with 66 elders suffering from
      chronic osteoarthritis pain. Differences in perceptions of pain were measured
      over 14 days in an experimental group who listened to music for 20 minutes daily
      and a control group who sat quietly for 20 minutes daily. All participants
      completed the Short Form McGill Pain Questionnaire (SF-MPQ) on day 1, 7, and 14
      of the study. RESULTS: Results of t-tests indicated that those who listened to
      music had less pain on both the Pain Rating Index on day 1 (P = 0.001), day 7 (P
      = 0.001) and day 14 (P = 0.001) and on the Visual Analogue Scale on day 1 (P =
      0.001), day 7 (P = 0.001) and day 14 (P = 0.001), when compared with those who
      sat quietly and did not listen to music. A repeated measure analysis of variance
      controlling for pretest measures demonstrated a significant decrease in pain
      among experimental group participants when compared with the control group on the
      pain descriptor section of the SF-MPQ (P = 0.001) and the visual analogue portion
      of the SF-MPQ (P = 0.001). CONCLUSION: Listening to music was an effective
      nursing intervention for the reduction of chronic osteoarthritis pain in the
      community-dwelling elders in this study.

PMID- 14651701
TI  - Caring for dying people in hospital.
AB  - BACKGROUND: Fifty-four per cent of people who die in England and Wales do so in
      hospital. Evidence suggests that care delivered to dying people in hospital does
      not match up to the ideal of a good death. These studies have provided
      organizational and structural explanations of nurses' behaviour that support
      argument for change at the macro level, in order to improve the quality of care
      delivered to dying people. There has been little study of the perceptions of
      nurses working in acute medical settings in relation to their experience of
      caring for dying people. Therefore, there is little evidence on which to base
      supportive strategies at the level of individual nurses. AIM: In this study we
      set out to develop an understanding of care for dying people in hospital, from
      the perspective of newly qualified staff nurses in the UK. The purpose was to
      build a theory of how nurses might be helped to deliver quality care to dying
      people in hospital. METHODS: This paper is based on an exploratory study
      underpinned by phenomenological philosophy. In-depth interviews were conducted
      with 28 newly qualified nurses, focusing on their experiences of caring for dying
      people on medical wards in two acute hospitals in England in 1999. The interview
      transcripts were interpreted using a phenomenological approach. FINDINGS: The
      findings presented in this paper relate to commonalities found to underlie study
      participants' perceptions of their experiences. All the nurses' stories were
      found to be built around six essences - the personal ideal, the actual, the
      unknown, the alone, tension and anti-tension. These essences, and the
      relationships between them, were used to build a model of the experience of
      caring for dying people in hospital. LIMITATIONS: This descriptive study of the
      experience of individual nurses does not examine the wider social context. It
      attempts to complement existing sociological theory of death and dying.
      CONCLUSION: The study revealed how a group of newly qualified nurses experienced
      caring for dying people. We theorize that the model developed has utility as a
      tool for gaining understanding of the experience of caring for dying people. It
      is assumed that nurses, through using this model to find explanations for their
      emotions and behaviours, may gain emotional support that might have a positive
      impact on the quality of care delivered to dying people in hospital.

PMID- 14651702
TI  - A comprehensive model for predicting burnout in Korean nurses.
AB  - BACKGROUND: Although burnout among nurses has been studied in a great deal, this
      work has not included Korean nurses. Furthermore, the role of personal resources
      such as empathy and empowerment in predicting the variance in burnout has never
      been examined. AIM: The purpose of this study was to understand the phenomenon of
      burnout among Korean nurses. A comprehensive model of burnout was examined to
      identify significant predictors among individual characteristics, job stress and
      personal resource, with the intention of providing a basis for individual and
      organizational interventions to reduce levels of burnout experienced by Korean
      nurses. METHODS: A cross-sectional correlational design was used. A sample of 178
      nurses from general hospitals in southern Korea was surveyed from May 1999 to
      March 2000. The data were collected using paper and pencil self-rating
      questionnaires and analysed using descriptive statistics, Pearson correlations,
      and hierarchical multiple regression. RESULTS: Korean nurses reported higher
      levels of burnout than nurses in western countries such as Germany, Canada, the
      United Kingdom and the United States of America. Nurses who experienced higher
      job stress, showed lower cognitive empathy and empowerment, and worked in night
      shifts at tertiary hospitals were more likely to experience burnout. CONCLUSIONS:
      Identifying a comprehensive model of burnout among Korean nurses is an essential
      step to develop effective managerial strategies to reduce the problem.
      Suggestions to reduce the level of burnout include enhancing nurses' cognitive
      empathy and perceived power, providing clear job descriptions and work
      expectations, and exploring nurses' shift preferences, especially at tertiary
      hospitals. In future research we recommend recruiting nurses from broader
      geographical areas using random selection in order to increase the
      generalizability of the findings.

PMID- 14651703
TI  - JAN Forum: your views and letters. Response to: Watson's guest editorial
      'Scientific methods are the only credible way forward for nursing research',
      Journal of advanced Nursing 43, 219-220.

PMID- 14651704
TI  - JAN Forum: your views and letters. Response to: Watson's guest editorial
      'Scientific methods are the only credible way forward for nursing research',
      Journal of advanced Nursing 43, 219-220.

PMID- 14651706
TI  - Supporting biosciences in the nursing curriculum: development and evaluation of
      an online resource.
AB  - AIMS: The aim of this project was to develop and evaluate an online resource
      designed to improve the biosciences knowledge of preregistration nursing
      students. BACKGROUND: A number of studies have identified lack of biological
      subject knowledge and anxiety about studying biosciences as serious problems for
      nursing students. The availability of a contextualized biological information
      resource prior to and early in their studies might help to reduce this fear and
      anxiety. METHODS: The project used an action research approach, involving an
      initial analysis of the extent of the problems with biosciences encountered by
      our nursing students, followed by the development and evaluation of a biology
      based open learning resource (entitled Headstart) in collaboration with
      preregistration nursing students and nurse educators. FINDINGS: The students in
      this study expressed a high level of concern about studying biology, and
      perceived this to be the most difficult aspect of their nursing programme
      (significantly more difficult than nursing practice). A significant correlation
      was also found between previous level of biological qualification and confidence
      in passing module tests. Evaluation of the new online resource illustrated the
      willingness of nursing students to use such a package, and general approval of
      its content and mode of delivery, despite a number of problems related to
      computer access and students' inexperience with information technology.
      CONCLUSIONS: This project has provided further evidence of the need for
      additional resources in biosciences for nursing students. It has also illustrated
      the way in which a targeted online resource has the potential to provide
      substantial benefits in terms of supporting the nursing curriculum. Whilst
      further evaluation is needed, the findings suggest that Headstart has the
      potential to address a number of issues identified both by this study and by
      previous research in nurse education.

PMID- 14651707
TI  - Postregistration genetics education provision for nurses, midwives and health
      visitors in the UK.
AB  - BACKGROUND: Rapid advances in genetics following the sequencing of the human
      genome will progressively reach all aspects of health care. Developments in
      genetics will increasingly having a significant influence on the work of nurses,
      midwives and health visitors. Therefore, these practitioners need to understand
      the impact that genetics will have for their patients and should be able to
      incorporate this new knowledge into their clinical practice to ensure that they
      continue to offer holistic care and influence the strategic development of health
      care. An earlier survey of higher education institutions in the United Kingdom
      (UK) offering preregistration courses for nurses, midwives and health visitors
      showed that the teaching of genetics was very limited in most curricula. AIM: To
      assess the provision of education on genetics for postregistration and
      postgraduate nurses, midwives and health visitors in the UK, as these
      practitioners are mostly likely to influence current health care provision and
      initiate changes in clinical practice. METHOD: A total of 38 higher education
      institutions from 11 regions were surveyed via telephone or e-mail, using a semi
      structured interview schedule. RESULTS: The findings showed that the inclusion of
      genetics in the curriculum was highly variable. A small number of institutions (n
      = 3) offered courses with whole modules on genetics, whereas 19 of the 38
      responding did not include any genetics in their curriculum at a postregistration
      level. CONCLUSION: The findings suggest that there is lack of recognition of the
      impact genetics is likely to have on health care. It is, therefore, recommended
      that the profile and relevance of genetics to nurses, midwives and health
      visitors should be promoted by the major organizations responsible for
      developing, commissioning and providing health care education.

PMID- 14651708
TI  - Myocardial infarction: gender differences in coping and social support.
AB  - AIM: The aim of this review is to summarize current knowledge about gender
      differences in perceptions of coping and social support among patients who have
      experienced myocardial infarction. RATIONALE: Women with coronary heart disease
      have physical, social and medical disadvantages compared with their male
      counterparts, which can influence their perception of recovery after cardiac
      events. No review has been found which focuses on gender differences in coping
      and social support in myocardial infarction patients. METHOD: A computerized
      search was conducted using the keywords 'myocardial infarction', 'coping',
      'gender differences' and 'social support'. Forty-one articles, published between
      1990 and October 2002, were scrutinized. FINDINGS: Two studies report that women
      used more coping strategies than men. Several qualitative studies found that
      women used a variety of coping strategies. Women minimized the impact of the
      disease, tended to delay in seeking treatment and did not want to bother others
      with their health problems. Household activities were important to them and aided
      their recovery. Men were more likely to involve their spouses in their recovery,
      and resuming work and keeping physically fit were important to them. Women tended
      to report that they had less social support up to 1 year after a myocardial
      infarction compared with men. They received less information about the disease
      and rehabilitation and experienced lack of belief in their heart problems from
      caregivers. Further, they received less assistance with household duties from
      informal caregivers. Men tended to report more support from their spouses than
      did women. CONCLUSIONS: Traditional gender-role patterns may influence the
      recovery of patients who have experienced myocardial infarction. Caregivers may
      need to be more sensitive to gender-specific needs with regard to risk profiles,
      social roles, and the patient's own role identity. For many women, especially
      older ones, household duties and family responsibilities may be an opportunity
      and a base for cardiac rehabilitation.

PMID- 14651709
TI  - Effects of acupuncture therapy on insomnia.
AB  - BACKGROUND: Acupuncture therapy, commonly used in clinical practice in oriental
      cultures, has the potential to produce a positive effect with patients
      experiencing insomnia. AIM: The purposes of this systematic review were: (1) to
      assess the trends across intervention studies using acupuncture for insomnia from
      1975 to 2002, (2) to examine dependent variables, and (3) to evaluate the effects
      of acupuncture therapy on insomnia in older people. METHOD: Data were collected
      from November 2001 to January 2003. A wide range of electronic databases was
      searched using the keywords 'insomnia', 'acupuncture' and 'experimental design'.
      Papers were included if they were published in the English language between 1975
      and 2002 and described an experimental study using acupuncture therapy to treat
      insomnia. Eleven reports met these criteria. FINDINGS: Most of the studies had
      been conducted since 1990. The findings showed that the first author was usually
      a Chinese medical doctor (n = 9) employed in a traditional department of
      medicine. Most of the papers were published in two journals: International
      Journal of Clinical Acupuncture and Journal of Traditional Chinese Medicine. Data
      were limited because of the small number of studies available. Half the studies
      had small samples (50 subjects or fewer), which were composed mainly of older
      women who had a variable duration of insomnia from 3 days to 34 years. The main
      method used to assess outcomes was questionnaire. All the studies reported
      statistically significant positive results. CONCLUSION: The results of this
      review suggest that acupuncture may be an effective intervention for the relief
      of insomnia. Further research, using a randomized clinical trial design, are
      necessary to determine the effectiveness of acupuncture. More work is also needed
      to promote the long-term therapeutic effects of acupuncture and to compare it
      with other therapies for insomnia.

PMID- 14651710
TI  - Patients' experiences of hip fracture.
AB  - BACKGROUND: Hip fracture is a major cause of mortality and morbidity,
      particularly among older people, but there is little information on how
      individuals experience this. AIMS: This study was conducted to explore the
      experiences of individuals who had suffered a hip fracture. The aim was not to
      produce generalizable findings but, rather, to generate a rich description of the
      experience of incurring and recovering from a hip fracture, to inform nursing
      practice. METHOD: Phenomenological methodology was used. A purposeful sample of
      five older patients was interviewed, following a stay in a community hospital for
      rehabilitation after surgical repair of a hip fracture. The unstructured
      interviews were tape-recorded, transcribed verbatim and analysed for significant
      statements and meanings. FINDINGS: Four major themes emerged: the injury
      experience, the pain experience, the recovery experience and the disability
      experience. The injury experience consisted of storytelling, recalling the
      experience of the injury itself. The pain experience consisted of coping with the
      pain. The recovery experience involved the operation, beginning the struggle of
      recovery, and regaining independence. The disability experience consisted of the
      disability itself, depending on others, and being housebound. CONCLUSIONS: Pain
      management, meeting psychological and physical needs for nursing care, planning
      for discharge, and ensuring a reasonable quality of life are areas for nursing
      care development. Consideration of appropriate settings for rehabilitation is
      needed and there should be further investigation into improving quality of life
      after discharge.

PMID- 14651711
TI  - Patients' perceptions of nursing care in the hospital setting.
AB  - BACKGROUND: Patient satisfaction and patient satisfaction with nursing care data
      are routinely collected as an indicator of the quality of services delivered.
      Despite the widespread collection and reporting of these data, the theoretical
      basis of patient satisfaction and patient satisfaction with nursing care remains
      unclear. Without a clear theoretical base, interpretation of patient satisfaction
      findings is hampered and the entire line of patient satisfaction research is of
      questionable validity. It has been suggested that, to understand patient
      satisfaction, patient perceptions of their care must first be understood. AIM:
      The aim of this study was to discover patients' perceptions of the nursing care
      they receive in the hospital setting. METHOD: Grounded theory method was used in
      this study of eight medical-surgical patients recently discharged from an
      academic medical centre in the south-eastern United States of America (USA).
      Participants were interviewed and the verbatim transcripts analysed using the
      constant comparative method. FINDINGS: Four categories of patient perceptions of
      their nursing care emerged from the data. 'Seeing the individual patient'
      captures the unique nature of the nursing care experience for each patient.
      'Explaining' represents the informal explanations given by nursing staff as they
      provide care. 'Responding' refers to both the character and timeliness of nursing
      staff's responses to patient requests or symptoms. 'Watching over' represents the
      surveillance activities of nursing staff. CONCLUSIONS: The categories identified
      in this study may be used in efforts to further develop a formal theory of
      patient satisfaction with nursing care. These categories should also be tested
      with patients possessing a wider range of characteristics, to assess the
      transferability of the findings.

PMID- 14651712
TI  - How the health visitor can help when problems between parents add to postnatal
      stress.
AB  - BACKGROUND: Caring for a baby can provoke or intensify discord between parents,
      with adverse effects on their own well-being and their parenting. AIM: The aim of
      this study was to appraise evidence obtained from 450 mothers on the quality of
      the parents' relationship during the postnatal period and the value of support
      provided by health visitors in cases of discord. DESIGN: The health visitors were
      based at nine clinics in an outer London borough, and had been trained on a four
      day course (the Brief Encounters course) to screen mothers for relationship
      problems at the 6-8-week check and to offer support (supportive listening,
      practical advice, referral) if problems were revealed. Data on relationship
      quality were obtained by a self-report screening scale completed at the 6-8-week
      check and again at the 12-week visit for immunizations, when the scale was
      included in a self-report questionnaire on help received from the health visitor.
      Intervention records kept by the health visitor showed what form any support had
      taken. Some 6 weeks later, 25 of the 82 mothers offered support, and their health
      visitors, were interviewed about their experience of the intervention. RESULTS:
      One in five mothers were identified as having a relationship problem at the 6-8
      week check. Most were offered support. One in five of the 351 mothers who
      completed a questionnaire at the 12-week visit reported receiving support in
      improving their relationship. The follow-up interviews showed that most mothers
      valued this support. Responses to a questionnaire completed by health visitors
      showed that most were enthusiastic about its benefits. CONCLUSIONS: A four-day
      training course for health visitors enabled them to screen for relationship
      problems during the postnatal period and to provide support when required in a
      way that was valued by mothers. Most health visitors were enthusiastic about the
      value of the intervention in improving their contribution to family welfare.

PMID- 14651713
TI  - Quality of life in adults with congenital ichthyosis.
AB  - BACKGROUND: Little is known about the quality of life of people with congenital
      and generalized skin diseases. Describing life history and quality of life from
      an individual perspective could increase understanding of living with generalized
      congenital ichthyosis for nursing staff and others. AIM: The aim of our study was
      to illustrate how middle-aged and older people with lamellar ichthyosis or
      epidermolytic hyperkeratosis describe the effects of their disease on their
      quality of life. METHODS: Six women and four men aged 56-80 years participated. A
      global clinical assessment of the severity of the disease was performed. The
      Nottingham Health Profile (NHP) questionnaire was used to investigate quality of
      life. Participants were interviewed face-to-face about childhood and adulthood
      experiences of living with a skin disease. Interview data were analysed using
      content analysis. RESULTS: Interview data were assigned to two categories,
      childhood and adulthood, and organized under 16 themes. All interviewees reported
      that their skin disease had affected them negatively to varying degrees during
      their entire lives, and that the most problematic period was childhood. Coping
      strategies used during childhood were hiding of the skin and developing shyness.
      There were no correlations between objective signs of ichthyosis and the NHP
      scores. CONCLUSIONS: Congenital ichthyosis appears to affect several aspects of
      life negatively, and it is hoped that an understanding of the effects of the
      disease will lead to more efficient nursing care.

PMID- 14651714
TI  - Translating clinical tools in nursing practice.
AB  - BACKGROUND: The widespread use of clinical tools in nursing practice reflects
      their usefulness in guiding patient care, evaluating treatment effectiveness and
      conducting audit. Cultural awareness and the provision of culturally competent
      care is a high priority for nurses in the United Kingdom (UK), given patterns of
      increasing ethnic diversity. However, meeting the individual needs of patients
      can be difficult when language barriers hinder communication. One way to address
      these difficulties is to translate existing clinical tools. AIM: The aim of this
      paper is to appraise the potential for, and limitations of, translating clinical
      tools for use in nursing practice. DISCUSSION: Drawing on a range of studies from
      the disciplines of health and social science, this review describes and discusses
      some key considerations relevant to translating clinical tools in nursing. These
      considerations include the need to ensure cultural equivalence, lack of
      familiarity with clinical tool formats in some cultures and its impact on
      responses, and low literacy levels in some populations. CONCLUSION: Clinical
      tools provide benefits in identifying patients' problems, guiding patient care,
      and evaluating treatments and interventions. Translating these tools can help to
      bridge the language gap that hinders good communication between nurses and
      patients. Translated clinical tools can be of acceptable cultural equivalence and
      validity if high quality translation methodologies are employed, together with an
      awareness of culturally relevant issues when interpreting the information gained
      from the tools.

PMID- 14651716
TI  - A response to the Editor's note 'Introduction to guidelines on reporting
      qualitative research' by Christine Webb (2003) Journal of Advanced Nursing 42,
      544-545.

PMID- 14651715
TI  - Rigour and grounded theory research.
AB  - BACKGROUND: Grounded theory methodology is a suitable qualitative research
      approach for clinical inquiry into nursing practice, leading to theory
      development in nursing. Given the variations in, and subjectivity attached to,
      the manner in which qualitative research is carried out, it is important for
      researchers to explain the process of how a theory about a nursing phenomenon was
      generated. Similarly, when grounded theory research reports are reviewed for
      clinical use, nurses need to look for researchers' explanations of their inquiry
      process. AIM: The focus of this article is to discuss the practical application
      of grounded theory procedures as they relate to rigour. METHOD: Reflecting on
      examples from a grounded theory research study, we suggest eight methods of
      research practice to delineate further Beck's schema for ensuring, credibility,
      auditability and fittingness, which are all components of rigour. FINDINGS: The
      eight methods of research practice used to enhance rigour in the course of
      conducting a grounded theory research study were: (1) let participants guide the
      inquiry process; (2) check the theoretical construction generated against
      participants' meanings of the phenomenon; (3) use participants' actual words in
      the theory; (4) articulate the researcher's personal views and insights about the
      phenomenon explored; (5) specify the criteria built into the researcher's
      thinking; (6) specify how and why participants in the study were selected; (7)
      delineate the scope of the research; and (8) describe how the literature relates
      to each category which emerged in the theory. CONCLUSIONS: The eight methods of
      research practice should be of use to those in nursing research, management,
      practice and education in enhancing rigour during the research process and for
      critiquing published grounded theory research reports.

PMID- 14651719
TI  - Pathology of drug-associated gastrointestinal disease.
AB  - A large number of drugs have gastrointestinal side-effects of which diarrhoea or
      constipation, nausea and vomiting are amongst the commonest. In relatively few
      are there diagnostic pathological changes and this review draws attention to the
      most common. Incriminating a drug as a cause of specific pathological changes
      requires the drug to be associated with the changes, for the latter to resolve
      when the drug is withdrawn and for them to re-appear when a patient is
      rechallenged with the drug. Individual histological features such as apoptosis,
      tissue infiltration by eosinophils and increased intra-epithelial lymphocytes
      within the gut mucosa can be clues to an iatrogenic aetiology but these are by no
      means specific. Amongst the few pathognomonic patterns of drug reactions is
      pseudomembranous colitis and diaphragm disease. These, along with others such as
      reactive gastritis and the collagenous and lymphocytic forms of microscopic
      colitis, in which drugs have also been implicated, are described here.

PMID- 14651720
TI  - Biopsy assessment of drug efficacy in the gastrointestinal tract.
AB  - When using biopsy pathology in clinical pharmacology to assess drug efficacy in
      the gastrointestinal tract, a number of questions must be answered: Is the biopsy
      necessary or more effective than macroscopic views by endoscopy? Can we extract
      maximal information from the specimen? Are there surrogate serum or other markers
      that give an overall measure of disease and/or improvement? Indeed,
      clinicopathological correlation is of paramount importance. If biopsy is to be
      used, it is important to utilize appropriate scoring systems. Many grading
      systems use continuous spectra, which are ordinal categorical variables and
      therefore a grading system of assigned 'numbers' which cannot be used in
      processes that require continuous variables such as linear regression. The use of
      grading vs a 'true' score with real numbers must be carefully considered, the
      site and number of biopsies must be precisely chosen and interobserver
      reproducibility of results evaluated before undertaking drug trials.
      Immunocytochemistry and in situ hybridization, however, can provide quantifiable
      molecular information related to mechanisms of drug action. The biopsy is of
      significant value as it is a true in vivo assessment if the above caveats are
      taken into account. However, further work is needed to determine sound
      histological criteria to assess the efficacy of drugs for use in gastrointestinal
      disease.

PMID- 14651721
TI  - Dose estimation for children.

PMID- 14651722
TI  - Comparison of combination inhalers vs inhaled corticosteroids alone in moderate
      persistent asthma.
AB  - AIMS: Inhalers combining long acting beta2-adrenoceptor agonists (LABA) and
      corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We
      evaluated the relative effects of LABA + ICS combination vs ICS alone on
      pulmonary function, bronchoprotection, acute salbutamol recovery following
      methacholine bronchial challenge, and surrogate inflammatory markers in patients
      with moderate persistent asthma. METHODS: Twenty-nine patients with mean FEV1 (+/
      SEM) of 78 +/- 3% predicted completed a randomized, double-blind, double-dummy,
      cross-over study. Patients received either 4 weeks of budesonide 400 microg +
      formoterol 12 microg (BUD + FM) combination twice daily followed by 1 week of BUD
      400 microg alone twice daily, or 4 weeks of fluticasone propionate 250 microg +
      salmeterol 50 microg (FP + SM) combination twice daily followed by 1 week of FP
      250 microg alone twice daily. Measurements were made at baseline and following
      each randomized treatment. RESULTS: FEV1 increase from pretreatment baseline as
      mean (+/- SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 +/
      1%) vs BUD (2 +/- 1%), and for FP + SM (8 +/- 1%) vs FP (2 +/- 1%). The fall in
      FEV1 following methacholine challenge as percentage change from prechallenge
      baseline FEV1 was not significantly different in all four groups; BUD + FM (22 +/
      1%), BUD (24 +/- 1%), FP + SM (23 +/- 1%) and FP (23 +/- 1%). Salbutamol
      recovery over 30 min following methacholine challenge as area under curve (AUC
      %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 +/- 35.5) vs BUD
      (281.1 +/- 52.8), and with FP + SM (553.1 +/- 34.1) vs FP (368.3 +/- 46.7). There
      were no significant differences between respective combination inhalers or
      between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum
      eosinophilic cationic protein (ECP) from baseline were not significantly
      different between treatments. CONCLUSIONS: Combination inhalers improve pulmonary
      function without potentiating anti-inflammatory effects on exhaled NO and serum
      ECP as compared with ICS alone, but delay acute salbutamol recovery after
      bronchoconstriction.

PMID- 14651723
TI  - Effect of the second-generation antihistamine, fexofenadine, on cough reflex
      sensitivity and pulmonary function.
AB  - AIMS: Current guidelines recommend the use of first-generation antihistamines for
      the treatment of cough due to rhinitis/postnasal drip syndrome. The antitussive
      activity of the second-generation antihistamine, fexofenadine, has not been
      investigated. Therefore, we evaluated the effect of fexofenadine on capsaicin
      induced cough in healthy volunteers and in subjects with acute viral upper
      respiratory tract infection (URI). METHODS: Twelve healthy volunteers and 12
      subjects with URI underwent pulmonary function testing and capsaicin cough
      challenge on two separate days, 2 h after ingesting 180 mg fexofenadine or
      matched placebo. Subjects inhaled single, vital-capacity breaths of capsaicin
      aerosol, administered in incremental doubling concentrations, until the
      concentration inducing five or more coughs (C5) was determined. RESULTS: In both
      subject groups, C5 was not significantly different after fexofenadine compared to
      placebo. In subjects with URI, pulmonary function studies were also similar. In
      healthy volunteers, however, FEV1 and FEF(25-75), pulmonary function parameters
      reflecting the degree of airway dilatation, were significantly increased after
      fexofenadine. Mean (95% CI) values for FEV1(L) after fexofenadine and placebo
      were 3.16 (2.77, 3.55) and 3.08 (2.69, 3.47), respectively (P = 0.017). Mean
      values for FEF(25-75)(L/s) were 3.49 (3.10, 3.88) and 3.26 (2.79, 3.72),
      respectively (P = 0.029). CONCLUSIONS: Fexofenadine demonstrated no antitussive
      activity against capsaicin-induced cough in healthy volunteers and subjects with
      URI. The ineffectiveness of fexofenadine in suppressing cough probably reflects
      the lack of anticholinergic activity and central nervous system penetrance that
      is characteristic of first-generation antihistamines. The mild bronchodilation
      induced by fexofenadine in healthy volunteers is of unclear clinical significance
      and requires further investigation.

PMID- 14651724
TI  - Evaluation of two carrier protein-angiotensin I conjugate vaccines to assess
      their future potential to control high blood pressure (hypertension) in man.
AB  - AIMS: We aim to modulate the renin-angiotensin system (RAS) by active
      immunization against angiotensin I hormone (AI), potentially providing a novel
      conjugate vaccine treatment for hypertension in man. METHODS: Immunization
      studies in rat and human subjects compare the effectiveness of tetanus toxoid
      (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following
      conjugation with an AI peptide analogue (AI). Cardiovascular responses were
      assessed in immunized rats and human subjects (two-dose trial only), following
      increasing i.v. infusions of either AI or angiotensin II hormone (AII). RESULTS:
      The AI-TT and AI-KLH conjugate vaccines induced an equivalent immune response,
      and inhibition of the pressor effects to exogenous AI in rats. Single-dose
      clinical trials with both conjugate vaccines only resulted in an immune response
      to the KLH carrier protein. A two-dose clinical trial of AI-KLH conjugate vaccine
      resulted in a significant immune response to AI. A shift in diastolic blood
      pressure (DBP) dose-response was demonstrated following challenge with AI and AII
      for the study volunteer showing the largest anti-AI IgG induction. CONCLUSION:
      KLH was shown to be a suitable alternative to TT as a carrier protein for AI,
      thus supporting continued evaluation of our AI-KLH conjugate vaccine for
      treatment of hypertension in man.

PMID- 14651725
TI  - The effects of KT3-671, a new angiotensin II (AT 1) receptor blocker in mild to
      moderate hypertension.
AB  - AIMS: To compare the antihypertensive effect, and tolerability and safety of once
      daily doses of KT3-671 with that of placebo in patients with mild to moderate
      uncomplicated essential hypertension. METHODS: A randomised, multicentre, double
      blind, parallel-group comparison of KT3-671 with placebo. Hypertensive patients
      [Ambulatory Blood Pressure Monitoring (ABPM), mean daytime DBP > 90 mmHg, Office
      sitting mean DBP 95-114 after a 7-28 day washout period] entered a 2-week, single
      blind, run-in phase. Patients eligible for the double-blind phase were randomised
      to receive KT3-671 40 mg, 80 mg, 160 mg or placebo once daily over 4 weeks. The
      primary end-point was trough mean sitting office DBP. The study had 90% power to
      detect a 5 mmHg change between treatments and placebo at the 5% level of
      significance. The secondary end-points were 24 hour, daytime and night time mean
      ABPM. RESULTS: Office DBP was significantly lower with KT3-671 40 mg but not the
      other 2 dosage groups (-3.2; 95% CL -6.1 : -0.3 P < 0.03). Office SBP was
      significantly reduced with all dosage groups (40 mg -5.9, 95% CL -11 : -0.9; 80
      mg -4.9, 95% CL -9.9 : 0.1 and 160 mg -5.7, 95% CL -10.8 : -0.7 P < 0.05). All
      doses of KT3-671 reduced systolic and diastolic ABPM. The number of patients with
      treatment related adverse events were comparable to placebo (38.8% KT3-671 vs
      32.8% placebo). There was some evidence of a dose-response relationship with fall
      in nocturnal ABPM. CONCLUSIONS: Oral KT3-671 was well tolerated. KT3-671 reduced
      office systolic BP at all doses and diastolic BP at some of the doses. Due to
      greater precision and power, the falls in mean ambulatory systolic and diastolic
      pressure were all significantly lower than placebo.

PMID- 14651726
TI  - Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in
      paediatric nephropathic cystinosis patients.
AB  - AIMS: Cysteamine is used to reduce tissue cystine content in patients suffering
      from nephropathic cystinosis. The objectives of the current study were to
      investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in
      children and young adults with nephropathic cystinosis. METHODS: Cysteamine
      bitartrate was administered to 11 cystinosis patients at their regular dose level
      in a single-dose, open-label, steady-state study. Blood samples were collected
      and analysed for plasma cysteamine and white blood cell cystine content and
      pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using
      a linked pharmacokinetic-pharmacodynamic model. RESULTS: Cysteamine was rapidly
      cleared from the plasma (mean CL/F = 32.3 ml min(-1) kg(-1), range = 17.3-52.2),
      appeared to be extensively distributed (mean Vss/F = 15.1 l, range 2.7-32.3) and
      exhibited a mean Tmax of 1.4 h. White blood cell cystine content post-dosing was
      significantly decreased compared with pre- and post-dose values (average
      decrement approximately 47%). A counter-clockwise hysteresis was noted in all
      patients, suggestive of a lag time (mean Tlag = 0.44 h, range 0.22-0.92) between
      drug concentration and effect. CONCLUSIONS: The results of this study establish
      that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing
      interval adequately maintains white blood cell cystine content below the target
      of 1 nmol cystine per mg protein.

PMID- 14651727
TI  - Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in
      human.
AB  - AIMS: To characterize the in vitro and in vivo inhibitory effect of stiripentol,
      a new anticonvulsant, on the metabolism of carbamazepine and saquinavir, which
      are substrates of CYP3A4. METHODS: Human liver microsomes and cDNA-expressed CYP
      enzymes were used for the in vitro experiments. Pharmacokinetic data from
      epileptic children and healthy adults were used for the carbamazepine and
      saquinavir in vivo studies, respectively. RESULTS: Carbamazepine
      biotransformation to its 10,11-epoxide by human liver microsomes (Vmax = 10.3
      nmol min(-1) nmol(-1) P450, apparent Km = 362 microm), cDNA-expressed CYP3A4
      (Vmax = 1.17 nmol min(-1) nmol(-1) P450, apparent Km = 119 microm) and CYP2C8
      (Vmax = 0.669 nmol min(-1) nmol(-1) P450, apparent Km = 757 microm) was inhibited
      by stiripentol (IC50 14, 5.1, 37 microM and apparent Ki 3.7, 2.5, 35 microm,
      respectively). Saquinavir biotransformation to its major metabolite M7 by human
      liver microsomes (Vmax = 5.7 nmol min(-1) nmol(-1) P450, apparent Km = 0.79
      microm) was inhibited by stiripentol (IC50 163 microM, apparent Ki 86 microm). In
      epileptic children treated with carbamazepine and stiripentol, the plasma
      concentration ratio of carbamazepine epoxide/carbamazepine was decreased by 65%.
      The in vivo apparent Ki for stiripentol ranged from 10.5 to 41.4 microm. The
      pharmacokinetics of saquinavir was not modified by stiripentol in healthy adults.
      The 95% confidence intervals for the difference for Cmax and AUC of saquinavir
      between the placebo and stiripentol phase were (-39.8, 39.8) and (-33.2, 112),
      respectively. CONCLUSIONS: These results showed that stiripentol was a weak
      inhibitor of saquinavir metabolism both in vitro and in vivo. In contrast,
      stiripentol is a potent inhibitor of carbamazepine 10,11-epoxide formation in
      vitro and in vivo in epileptic patients.

PMID- 14651729
TI  - Free and bound propofol concentrations in human cerebrospinal fluid.
AB  - AIMS: The aim of this study was to define the relationship between unbound
      propofol concentrations in plasma and total drug concentrations in human
      cerebrospinal fluid (CSF), and to determine whether propofol exists in the CSF in
      bound form. METHODS: Forty-three patients (divided into three groups) scheduled
      for elective intracranial procedures and anaesthetized by propofol target control
      infusion (TCI) were studied. Blood and CSF samples (taken from the radial artery,
      and the intraventricular drainage, respectively) from group I (17 patients) were
      used to investigate the relationship between unbound propofol concentration in
      plasma and total concentration of the drug in CSF. CSF samples taken from group
      II (18 patients) were used to confirm the presence of the bound form of propofol
      in this fluid. The CSF and blood samples taken from group III (eight patients)
      were used to monitor the course of free and bound CSF propofol concentrations
      during anaesthesia. RESULTS: For group I patients the mean (and 95% confidence
      interval) total plasma propofol concentration was 6113 (4971, 7255) ng ml(-1),
      the mean free propofol concentration in plasma was 63 (42, 84) ng ml(-1), and the
      mean total propofol concentration in CSF was 96 (76, 116) ng ml(-1) (P < 0.05 for
      the difference between the last two values). For group II patients the fraction
      of free propofol in CSF was 31 (26, 37)%. For group III patients the fraction of
      free propofol in CSF during TCI was almost constant (about 36%). CONCLUSIONS: The
      unbound propofol concentration in plasma was not equal to its total concentration
      in CSF and cannot be directly related to the drug concentration in the brain.
      Binding of propofol to components of the CSF may be an additional mechanism
      regulating the transport of the drug from blood into CSF.

PMID- 14651728
TI  - An in vitro interethnic comparison of monoamine oxidase activities between
      Japanese and Caucasian livers using rizatriptan, a serotonin receptor 1B/1D
      agonist, as a model drug.
AB  - AIMS: Monoamine oxidase (MAO) is located in human liver, and catalyses the
      oxidative deamination step of many xenobiotics. However, whether there exists an
      interethnic difference in MAO activities has, to our knowledge, not been
      clarified. We aimed to assess the MAO type A (MAO-A) involvement in the metabolic
      pathway of rizatriptan (RIZ), an antimigraine 5-hydroxytryptamine (5-HT)1B/1D
      agonist, and the interethnic difference in MAO activities between Caucasians and
      Japanese using RIZ as a model drug in in vitro experiments. METHODS: Oxidative
      deaminase activities were determined with the subcellular fractions of Japanese
      livers and the microsomal fraction of Caucasian livers using RIZ, 5-HT (MAO-A
      substrate) and 2-phenylethylamine (PEA) (MAO-B substrate) as substrates. RESULTS:
      The oxidative deaminase activities of RIZ vs. 5-HT were highly (r = 0.87 and
      0.96, P < 0.001) correlated with each other in both the microsomal and
      mitochondrial fractions of Japanese livers. Subsequent results were obtained from
      in vitro experiments using liver microsomes based upon these findings. The
      oxidative deaminase activities of RIZ were inhibited completely by the nanomolar
      order concentration of clorgyline and Ro 41-1049 (MAO-A selective inhibitors),
      but not by that of Ro 16-6491 (MAO-B selective inhibitor). The majority of the
      mean Michaelis-Menten values for three substrates toward MAO obtained from six
      Japanese and six Caucasian liver microsomes reached no significant differences
      between the two ethnic groups. The mean microsomal oxidative deaminase activities
      assessed in 18 Japanese and 20 Caucasian livers using the three substrates also
      showed no significant differences between the two ethnic groups. CONCLUSIONS: RIZ
      is mainly metabolized by MAO-A and the in vitro oxidative deaminase activities
      mediated via MAO-A and -B do not appear to differ between Japanese and
      Caucasians.

PMID- 14651730
TI  - Human subcutaneous tissue distribution of fluconazole: comparison of
      microdialysis and suction blister techniques.
AB  - AIMS: To investigate uptake of fluconazole into the interstitial fluid of human
      subcutaneous tissue using the microdialysis and suction blister techniques.
      METHODS: A sterile microdialysis probe (CMA/60) was inserted subcutaneously into
      the upper arm of five healthy volunteers following an overnight fast. Blisters
      were induced on the lower arm using gentle suction prior to ingestion of a single
      oral dose of fluconazole (200 mg). Microdialysate, blister fluid and blood were
      sampled over 8 h. Fluconazole concentrations were determined in each sample using
      a validated HPLC assay. In vivo recovery of fluconazole from the microdialysis
      probe was determined in each subject by perfusing the probe with fluconazole
      solution at the end of the 8 h sampling period. Individual in vivo recovery was
      used to calculate fluconazole concentrations in subcutaneous interstitial fluid.
      A physiologically based pharmacokinetic (PBPK) model was used to predict
      fluconazole concentrations in human subcutaneous interstitial fluid. RESULTS:
      There was a lag-time (approximately 0.5 h) between detection of fluconazole in
      microdialysate compared with plasma in each subject. The in vivo recovery of
      fluconazole from the microdialysis probe ranged from 57.0 to 67.2%. The
      subcutaneous interstitial fluid concentrations obtained by microdialysis were
      very similar to the unbound concentrations of fluconazole in plasma with maximum
      concentration of 4.29 +/- 1.19 microg ml(-1) in subcutaneous interstitial fluid
      and 3.58 +/- 0.14 microg ml(-1) in plasma. Subcutaneous interstitial fluid-to
      plasma partition coefficient (Kp) of fluconazole was 1.16 +/- 0.22 (95% CI 0.96,
      1.35). By contrast, fluconazole concentrations in blister fluid were
      significantly lower (P < 0.05, paired t-test) than unbound plasma concentrations
      over the first 3 h and maximum concentrations in blister fluid had not been
      achieved at the end of the sampling period. There was good agreement between
      fluconazole concentrations derived from microdialysis sampling and those
      estimated using a blood flow-limited PBPK model. CONCLUSIONS: Microdialysis and
      suction blister techniques did not yield comparable results. It appears that
      microdialysis is a more appropriate technique for studying the rate of uptake of
      fluconazole into subcutaneous tissue. PBPK model simulation suggested that the
      distribution of fluconazole into subcutaneous interstitial fluid is dependent on
      tissue blood flow.

PMID- 14651731
TI  - Ultramolecular homeopathy has no observable clinical effects. A randomized,
      double-blind, placebo-controlled proving trial of Belladonna 30C.
AB  - AIMS: To investigate if ultramolecular homeopathy has any clinical effects. This
      was assessed using the proving of the homeopathic remedy Belladonna given at an
      ultramolecular dose (30C), as a model. A proving states that when a homeopathic
      remedy is given to a healthy person, they will experience symptomatic effects
      specific to that remedy. If ultramolecular doses are clinically active, the
      Belladonna 30C group should experience more true Belladonna proving symptoms than
      the placebo group. METHODS: Healthy subjects (n = 253), aged 18-30 years, took
      part in this double-blind, randomized placebo-controlled study. Total study
      duration was 4 weeks. Subjects were randomized before 1 week placebo run-in. They
      received 2 weeks of treatment intervention (Belladonna 30C or placebo) and were
      followed up for 1 week. Subjects recorded any symptoms experienced during the
      total study period on a daily basis using a structured questionnaire. Symptom
      diaries were analysed blind to determine if each subject had proved or not (based
      on predefined criteria). The main outcome was the proportion of subjects who had
      proved in each treatment group. RESULTS: No significant group differences in
      proving rates were observed [Belladonna provers N = 14 (13.9%); placebo provers N
      = 15 (14.3%); mean difference -0.4%, 95% confidence interval -9.3, 10.1] based on
      intention to treat analysis. Primary outcome was not affected by seasonality or
      the individual's attitude to complementary medicine. CONCLUSION: Ultramolecular
      homeopathy had no observable clinical effects.

PMID- 14651732
TI  - Changes in antipsychotic drug prescribing by general practitioners in the United
      Kingdom from 1991 to 2000: a population-based observational study.
AB  - AIM: To estimate changes in the frequency of use of various antipsychotic drugs
      in the UK from 1991 to 2000 and to relate these changes to patients'
      characteristics. METHODS: We conducted a population-based observational study
      using data from general practices that contribute information to the General
      Practice Research Database (GPRD). The study population comprised men and women
      10-99 years old. We estimated annual use, first-time use, duration of use and, in
      a sample of 200 patients, indications for use of various antipsychotic drugs, and
      we observed how these measures had changed over the past decade. RESULTS: The
      annual use of antipsychotic drugs increased from 10.5 per thousand in 1991 to
      12.2 per thousand in 2000, an overall increase of 16%. The increase was greater
      in men (25.2%) than women (2.7%). At the same time, the rate of new use of
      antipsychotic drugs was stable in men and decreased by 21% in women. The
      difference between patterns of annual use and rates of new use is attributable to
      the increasing average annual duration of treatment in both men and women during
      the past decade. Thioridazine, which the UK Committee on the Safety of Medicines
      (CSM) recently recommended should be used only for second-line treatment of
      schizophrenia in adults, was the most commonly prescribed antipsychotic
      throughout the study period. Its use increased as a proportion of all
      antipsychotic drug use from 1991 to 2000 in men and women aged 10-69 years, but
      decreased in older users. More than half of all first-time use of antipsychotic
      drugs in the sample of patients we evaluated was for treatment of depression,
      anxiety states, and panic disorders, while less than 10% was for treatment of
      schizophrenia and other psychoses. CONCLUSION: The use of antipsychotic drugs has
      increased in the UK during the past decade, primarily due to increased average
      annual duration of use rather than higher rates of new use. Most antipsychotic
      drug use appears to have been prescribed to treat nonpsychotic disorders. It will
      be of interest to see whether the use of thioridazine, which was the most widely
      prescribed antipsychotic during 1991-2000, decreases during the next decade in
      response to the recent CSM recommendation.

PMID- 14651733
TI  - Quinine intoxications reported to the Scottish Poisons Information Bureau 1997
      2002: a continuing problem.
AB  - Quinine is widely prescribed in the UK for night cramps. Its potential toxicity
      in overdose is well known. We have reviewed the Scottish experience of enquiries
      regarding quinine overdose to the poisons information service responsible for
      Scotland over a 6-year period. Between 1997 and 2002 there were 96 reports of
      suspected quinine toxicity from Scotland (population 5.2 million), 19 of which
      were in children. The largest quantities of drug ingested were in patients
      between the ages of 11 and 30. In comparison with older studies the pattern of
      quinine poisoning does not appear to have changed in the UK over 20 years,
      despite recognition that it is a toxic agent in overdose, and particularly in
      children.

PMID- 14651736
TI  - Neonatal intraventricular haemorrhage associated with maternal use of paroxetine.
AB  - Selective serotonin reuptake inhibitors (SSRIs) have been reported to inhibit
      serotonin uptake into platelets, resulting in decreased platelet function. We
      report a case of a large intraventricular haemorrhage in a 6-h-old boy, whose
      mother used paroxetine during pregnancy.

PMID- 14651737
TI  - Serum sickness-like reaction associated with clopidogrel.

PMID- 14651739
TI  - Stem cells and immunotherapy.

PMID- 14651740
TI  - Exploitation of stem cell plasticity.
AB  - For many years, adult haemopoietic stem cells (HSCs) have been considered
      'plastic' in their proliferative and differentiation capacities. Recently,
      evidence that supports newer concepts of adult stem cell plasticity has been
      reported. In particular, stem cells from haemopoietic tissues seem to have
      'extraordinary' abilities to generate or switch between haemopoietic and
      nonhaemopoietic lineages, exhibiting an unexpected degree of developmental or
      differentiation potential. The mechanisms by which cell fate reprogramming occurs
      are still poorly understood. Nevertheless, an increasing number of studies is
      challenging one of the main dogmas in biology, namely that mammalian cell
      differentiation follows established programmes in a hierarchical fashion, and
      once committed to a particular somatic cell lineage, cells do not change into
      another somatic lineage. The 'nonhierarchical', 'reversible' phenotype of stem
      cells in haemopoietic tissues, if it exists, would be an advantage that could be
      exploited in regenerative medicine. Here, we review the recent advances in HSC
      biology and discuss the general concepts of adult stem cell plasticity with
      respect to these cells and how these might be exploited clinically.

PMID- 14651741
TI  - Stem cells for the treatment of neurological disease.
AB  - Stem cells are widely believed to have significant potential in the treatment of
      human disease. Comments such as '[stem cells]...could prove the Holy Grail in
      finding treatments for cancer, Parkinson's disease, diabetes, osteoporosis,
      spinal cord injuries, Alzheimer's disease, leukaemia and multiple
      sclerosis...transform[ing] the lives of hundreds of thousands of people' (Yvette
      Cooper, Public Health minister, quoted in The Times, December 16 2000, authors'
      italics) serve to reinforce the extraordinary expectations of stem cells,
      particularly in neurological disease. Stem cells, traditionally defined as clone
      forming, self-renewing, pluripotent, progenitor cells, have already proved
      themselves to be an invaluable source of transplantation material in several
      clinical settings, most notably malignant haematology, and attention is now
      turning to a wider variety of diseases in which there may be potential for
      therapeutic intervention with stem cell transplantation. Neurological diseases
      have been highlighted as a priority and this is understandable given their
      unenviable reputation for relentless progression and the paucity of disease
      modifying treatments. However, it is important that the potential of stem cells
      to treat neurological disease is critically appraised if the hopes of patients
      and doctors are not to be raised without foundation.

PMID- 14651742
TI  - Leukaemic stem cells.
AB  - All haemopoietic cell lineages arise from multipotential self-renewing stem cells
      that give rise to committed progenitor cells. These progenitor cells subsequently
      differentiate into more lineage-committed cells with a restricted range of
      plasticity. A hierarchical order is considered to exist, where lineage commitment
      and differentiation are thought to be irreversible. As cells differentiate, they
      gradually lose the ability to self-renew. The most primitive haemopoietic
      progenitor cells have the ability to reconstitute long-term haemopoiesis in
      myeloablated recipients. However, as cells differentiate, there is an
      orchestrated silencing of some genes and activation of others, resulting in
      lineage commitment and generally a reduction in proliferative ability. Here, we
      discuss potential differences between normal and leukaemic stem cells, some of
      which may have therapeutic implications.

PMID- 14651743
TI  - Stem cells in paroxysmal nocturnal haemoglobinuria and aplastic anaemia:
      increasing evidence for overlap of haemopoietic defect.
AB  - The clinical association between paroxysmal nocturnal haemoglobinuria (PNH) and
      aplastic anaemia (AA) has long been recognized. Haemolytic PNH, as confirmed by a
      positive Ham's test, can occur in the setting of AA, and conversely AA can be a
      late complication of PNH. With the development of sensitive flow cytometry to
      quantify the expression of phosphatidylinositolglycan (PIG)-anchored proteins on
      blood cells, a small PNH clone can now be detected in a large number of patients
      with AA at diagnosis. PIG-A gene mutations can also be demonstrated in some AA
      patients. In haemolytic PNH, there is always marrow suppression despite a
      morphologically cellular marrow. In vitro cultures show markedly diminished
      proliferative capacity in both short-term and long-term marrow cultures, similar
      to that seen in AA. A similar autoimmune process, through the T-cell cytotoxic
      repertoire, is probably responsible for the pathogenesis of both AA and PNH. PIG
      deficient cells may be resistant to immunological attack by autoreactive
      cytotoxic T cells, because they lack PIG. They are also more resistant to
      apoptosis than the PIG-normal cell population. This results in the selection of
      the PIG-deficient clone, in contrast to the PIG-normal stem cells which possess
      the PIG anchor and hence are targeted and depleted by the autoreactive T cells.

PMID- 14651744
TI  - New advances in acute graft-versus-host disease prophylaxis.
AB  - Immunocompetent donor T cells in Allogeneic Haematopoietic Stem Cell grafts
      mediate acute Graft versus Host Disease (GvHD), still a major cause of recipient
      morbidity and mortality post transplant. Despite the advent of high resolution
      HLA-typing and matching at HLA loci, acute GvHD remains a significant problem,
      even in HLA matched siblings, due primarily to minor histocompatability antigen
      mismatches. Treatment of GvHD remains ineffective and highly immunosuppressive
      and the challenge to find effective methods of prevention continues. Non
      selective removal of donor T cells from the graft has been proven to be effective
      in preventing GvHD but the beneficial effects of donor T cells, namely effective
      immune reconstitution and anti tumour activity, are lost. This review considers
      mechanisms by which acute GvHD may be prevented in the context of the current
      model of GvHD immunopathogenesis, with a special emphasis on the recent
      techniques of selective removal or destruction of donor allogeneic T cells that
      have been described.

PMID- 14651745
TI  - Natural killer cells in haematopoietic stem cell transplantation.
AB  - Natural killer cells represent the predominant lymphoid cell in the peripheral
      blood for many months after allogeneic or autologous stem cell transplant and
      their role in immunity to pathogens during this period is established. However,
      following the largely unsuccessful trials of NK and IL-2 activated NK cells for
      the treatment of haematological malignancies in the 1980's and 90's, their role
      in tumour immunology was discredited. Over the past ten years we have come to
      understand some of the complex regulatory pathways involved in NK cell activation
      and we are now in a position to capitalise upon this knowledge. This review
      presents our current state of understanding of NK cell regulation and highlights
      the role of these cells in engraftment, graft-versus-host disease, anti-leukaemia
      activity and post-transplant infection.

PMID- 14651746
TI  - The cellular immunotherapy of viral infection.
AB  - Viral infections remain a major problem for the patient who has undergone a stem
      cell transplant and the introduction of increasingly more intensive SCT regimens
      suggests that this will remain a significant concern for the immediate future.
      Advances in basic immunology have led to an improved understanding of how immune
      responses control individual viral infections and this information is now being
      directly applied to patient care with encouraging results. The application of
      cellular immunotherapy to the immunocompromised patient is one of the most
      exciting areas of clinical medicine and offers the prospect of significant
      clinical impact.

PMID- 14651747
TI  - Quality issues in stem cell and immunotherapy laboratories.
AB  - The advent of the Code of Practice for Tissue Banks has led to the requirement
      for quality systems to be established in all laboratories involved in the
      production or processing of all cellular tissues to be used therapeutically. The
      quality system is all-encompassing from process validations and quality assurance
      to the standard of facilities and staff training. This seems self-evident to
      those working within the transfusion field but is a relatively novel concept to
      many hospital laboratories preparing transplant products such as bone marrow or
      peripheral blood derived haematopoietic stem cells. This review places the
      current guidelines in an historical context and explains many of the central
      tenets and requirements of the Code of Practice while outlining a process to
      facilitate preparation for accreditation.

PMID- 14651748
TI  - Potential involvement of the immune system in the development of endometriosis.
AB  - This article presents an overview of immunological factors and their role in the
      development of endometriosis, with emphasis on inflammatory cytokines, growth and
      adhesion factors. Although retrograde menstruation is a common phenomenon among
      women of reproductive age, not all women who have retrograde menstruation develop
      endometriosis. The development of endometriosis is hypothesised to be a complex
      process, which may be facilitated by several factors, including the quantity and
      quality of endometrial cells in peritoneal fluid (PF), increased inflammatory
      activity in PF, increased endometrial-peritoneal adhesion and angiogenesis,
      reduced immune surveillance and clearance of endometrial cells, and increased
      production of autoantibodies against endometrial cells. Potential biomarkers like
      cytokines and autoantibodies upregulated during development of endometriosis may
      be useful in the development of a non-surgical diagnostic tool. Although
      endometriosis can be treated using hormonal suppression, there is need for non
      hormonal drugs, which can inhibit the development of endometriosis and alleviate
      pain or infertility without inhibition of ovulation. New molecules that modulate
      immune function in endometriosis should be the targets for future research.

PMID- 14651750
TI  - Tolerance of the fetus by the maternal immune system: role of inflammatory
      mediators at the feto-maternal interface.
AB  - The adaptive immune system of placental mammals has evolved to tolerate the
      fetus. Rejection of the fetus by adaptive immune responses is therefore a rare
      event, with abortion being caused more frequently by inflammation in the
      placenta. This review will cover recent aspects of immune privilege and the
      innate immune system at the feto-maternal interface, citing examples of the role
      played by microbial infections in fetal demise.

PMID- 14651749
TI  - Immunology of term and preterm labor.
AB  - During pregnancy there is an alteration in maternal immunity within the uterus
      where innate, proinflammatory immune responses are tightly regulated to prevent
      immunological rejection of the fetal allograft. Disruption of the delicate
      balance of cytokines by bacteria or other factors increases the production of
      proinflammatory cytokines at the maternal-fetal interface and activates the
      parturition mechanism prematurely. Despite years of searching, there is still no
      broadly effective strategy for preventing preterm labor and most therapies are
      directed at inhibiting myometrial contractions and improving neonatal outcome.
      Recent studies with progestins and interleukin-10 (IL-10), however, are showing
      promise in randomized clinical trials and animal studies. Furthermore, the
      identification of the Toll-like receptors as upstream mediators of inflammation
      may offer alternative therapeutic targets for preventing this common pregnancy
      complication.

PMID- 14651751
TI  - Pregnancy and gamma/delta T cells: taking on the hard questions.

PMID- 14651752
TI  - Potential role of macrophages as immunoregulators of pregnancy.
AB  - The role of the maternal immune system during pregnancy has focused mainly on the
      aspect of immune tolerance to the invading trophoblast and, therefore, fetus.
      While this is a critical aspect of reproductive immunology, it is also important
      to consider the function of the maternal immune system in the promotion of
      implantation and maintenance of pregnancy. Apoptosis or cell death is not the
      final stage in tissue development. The quick and effective removal of apoptotic
      cells by tissue macrophages represents a vital process preventing "leak" of self
      antigens and promoting the production of proliferative/survival factors. One of
      the key requirements of apoptotic cell clearance is the resolution of
      inflammatory conditions, which, as in the case of pregnancy, may have lethal
      consequences. This review will focus on decidual macrophages and their role on
      apoptosis and cell clearance during pregnancy.

PMID- 14651753
TI  - Vaccines against sexually transmitted diseases.

PMID- 14651754
TI  - Medication use by persons with chronic fatigue syndrome: results of a randomized
      telephone survey in Wichita, Kansas.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by profound fatigue,
      which substantially interferes with daily activities, and a characteristic
      symptom complex. Patients use a variety of prescribed and self-administered
      medications, vitamins, and supplements for relief of their symptoms. The
      objective of this study was to describe utilization of medications and
      supplements by persons with CFS and non-fatigued individuals representative of
      the general population of Wichita, Kansas. METHODS: We used a random-digit
      dialing telephone survey to identify persons with CFS in the general population
      of Wichita, Kansas. Subjects who on the basis of telephone interview met the CFS
      case definition, and randomly selected non-fatigued controls, were invited for a
      clinic evaluation that included self-reported use of medications and supplements.
      Sex-adjusted odds ratios and 95% confidence interval were estimated to measure
      the association between CFS and use of various drug categories. RESULTS: We
      clinically evaluated and classified 90 subjects as CFS during the study and also
      collected clinical data on 63 who never described fatigue. Subjects with CFS
      reported using 316 different drugs compared to 157 reported by non-fatigued
      controls. CFS subjects were more likely to use any drug category than controls (p
      = 0.0009). Pain relievers and vitamins/supplements were the two most common
      agents listed by both groups. In addition CFS persons were more likely to use
      pain relievers, hormones, antidepressants, benzodiazepines, gastro-intestinal,
      and central nervous system medications (Sex-adjusted odds ratios range = 2.97 -
      12.78). CONCLUSION: Although the reasons for increased use of these agents were
      not elucidated, the data indicated the CFS patients' need for symptom relief.

PMID- 14651755
TI  - Critical appraisal skills of family physicians in Ontario, Canada.
AB  - BACKGROUND: Our primary objective in this study was to measure family physicians'
      knowledge of the key elements that go into assessing the validity and
      interpreting the results in three different types of studies: i) a randomized
      controlled trial (RCT); ii) a study evaluating a diagnostic test; and iii) a
      systematic review (SR). Our secondary objectives were to determine the
      relationship between the above skills and age, gender, and type of practice.
      METHODS: We obtained a random sample of 1000 family physicians in Ontario from
      the College of Family Physicians of Canada database. These physicians were sent a
      questionnaire in the mail with follow-up mailings to non-responders at 3 and 8
      weeks. The questionnaire was designed to measure knowledge and understanding of
      the basic concepts of critical appraisal skills. Based on the responses to the
      questions an Evidence Based Medicine (EBM) Knowledge Score was determined for
      each physician. RESULTS: A response rate of 30.2% was achieved. The respondents
      were younger and more likely to be recent graduates than the population of
      Ontario Family Physicians as a whole. This was an expected outcome. Just over 50%
      of respondents were able to answer questions concerning the critical appraisal of
      methods and the interpretation of results of research articles satisfactorily.
      The average score on the 12-point EBM Knowledge Scale was 6.4. The younger
      physicians scored higher than the older physicians, and academic physicians
      scored higher than community-based physicians. Scores of male and female
      physicians did not differ. CONCLUSIONS: We have shown that in a population of
      physicians which is younger than the general population of physicians, about 50%
      have reasonable knowledge regarding the critical appraisal of the methods and the
      interpretation of results of a research article. In general, younger physicians
      were more knowledgeable than were older physicians. EBM principles were felt to
      be important to the practice of medicine by 95% of respondents.

PMID- 14651756
TI  - The utility of cytokeratins 7 and 20 (CK7/20) immunohistochemistry in the
      distinction of short-segment Barrett esophagus from gastric intestinal
      metaplasia: Is it reliable?
AB  - BACKGROUND: The purpose of the present correlative immunohistochemical study was
      to assess the utility of cytokeratin (CK7 and CK20) expression in the diagnosis
      of short-segment Barrett esophagus, particularly its efficacy in differentiating
      Barrett mucosa from intestinal metaplasia of the gastric cardia and corpus.
      METHODS: Two groups of endoscopic biopsy specimens were examined, including 20
      endoscopic biopsy specimens of short-segment Barrett esophagus (Group A) and
      equal number exhibiting Helicobacter pylori associated intestinal metaplasia of
      the gastric cardia and corpus (Group B). All were investigated by
      immunohistochemistry using the standard ABC method for CK7 and CK20 expression.
      Fisher's exact test was used for statistical analysis of Barrett CK7/20 and
      gastric CK7/20 patterns between the groups. RESULTS: The anticipated pattern of
      reactivity in Barrett mucosa (CK7: strong diffuse positivity in superficial and
      deep glands; CK20: positivity in surface epithelium and superficial glands) was
      seen in 2 cases of Group A specimens. The expected gastric pattern (CK7: patchy
      immunostaining with variable involvement of deep glands; CK20: patchy
      immunostaining of superficial and deep glands in incomplete intestinal metaplasia
      / absence of CK7 immunoreactivity with strong CK20 staining in superficial and
      deep glands in complete intestinal metaplasia) was seen in 8 cases of Group B
      specimens. The respective sensitivity and false-negativity values of CK7/20
      staining for Barrett pattern in Group A were 10% and 90%, respectively. These
      values for gastric pattern in Group B were 40% and 60%, respectively. The
      specificity and false-positivity values of both patterns were same (100% and 0%,
      respectively). There was no statistically significant difference for Barrett
      pattern between the two groups (P = 0.487), while the observation of gastric
      pattern was significantly higher in Group B than in Group A (P = 0.02).
      CONCLUSIONS: We concluded that these hypothesized and recently applied diagnostic
      criteria involving CK7 and CK20 immunoreactivity are not reliable in
      distinguishing short-segment Barrett esophagus from intestinal metaplasia as seen
      in gastric cardia and corpus.

PMID- 14651757
TI  - Tumor classification and marker gene prediction by feature selection and fuzzy c
      means clustering using microarray data.
AB  - BACKGROUND: Using DNA microarrays, we have developed two novel models for tumor
      classification and target gene prediction. First, gene expression profiles are
      summarized by optimally selected Self-Organizing Maps (SOMs), followed by tumor
      sample classification by Fuzzy C-means clustering. Then, the prediction of marker
      genes is accomplished by either manual feature selection (visualizing the
      weighted/mean SOM component plane) or automatic feature selection (by pair-wise
      Fisher's linear discriminant). RESULTS: The proposed models were tested on four
      published datasets: (1) Leukemia (2) Colon cancer (3) Brain tumors and (4) NCI
      cancer cell lines. The models gave class prediction with markedly reduced error
      rates compared to other class prediction approaches, and the importance of
      feature selection on microarray data analysis was also emphasized. CONCLUSIONS:
      Our models identify marker genes with predictive potential, often better than
      other available methods in the literature. The models are potentially useful for
      medical diagnostics and may reveal some insights into cancer classification.
      Additionally, we illustrated two limitations in tumor classification from
      microarray data related to the biology underlying the data, in terms of (1) the
      class size of data, and (2) the internal structure of classes. These limitations
      are not specific for the classification models used.

PMID- 14651759
TI  - Chronic obstructive pulmonary disease: definition and epidemiology.
AB  - Chronic obstructive pulmonary disease (COPD) continues to cause a heavy health
      and economic burden in the United States and around the world. Some of the risk
      factors for COPD are well known and include smoking, occupational exposures, air
      pollution, airway hyperresponsiveness, asthma, and certain genetic variations,
      although many questions remain, such as why < 20% of smokers develop substantial
      airway obstruction. There are several different definitions of COPD and the
      definitions depend on accurate diagnosis. Small differences in the definition can
      have large effects on the estimates of COPD in the population. In addition, newer
      measures, such as functional status or exercise capability, have emerged as
      important in determining the prognosis of COPD patients. Furthermore, evidence
      continues to emerge that COPD represents several different disease processes,
      with potentially different interventions required. In most of the world COPD
      prevalence and mortality are still increasing and will probably continue to rise
      in response to increases in smoking, particularly by women and adolescents.
      Resources aimed at smoking cessation and prevention, COPD education, early
      detection, and better treatment will be of the most benefit in our continuing
      efforts against this important cause of morbidity and mortality.

PMID- 14651760
TI  - Strategies for screening for chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease is easily detected in its preclinical
      phase, using office spirometry. Successful smoking cessation prevents further
      disease progression in most patients. Spirometry measures the ratio of the forced
      expiratory volume in the first second to the forced vital capacity (FEV(1)/FVC),
      which is the most sensitive and specific test for detecting airflow limitation.
      Primary care practitioners see the majority of adult smokers, but few primary
      care practitioners currently have spirometers or regularly order spirometry for
      their smoker patients. Improvements in spirometry software have made it much
      easier to obtain good quality spirometry test sessions, thereby reducing the
      misclassification rate. Respiratory therapists and pulmonary function
      technologists can help primary care practitioners select good office spirometers
      for identifying chronic obstructive pulmonary disease and teach staff how to use
      spirometers correctly.

PMID- 14651761
TI  - Exacerbations of chronic obstructive pulmonary disease.
AB  - Exacerbations of chronic obstructive pulmonary disease (COPD) cause morbidity,
      hospital admissions, and mortality, and strongly influence health-related quality
      of life. Some patients are prone to frequent exacerbations, which are associated
      with considerable physiologic deterioration and increased airway inflammation.
      About half of COPD exacerbations are caused or triggered primarily by bacterial
      and viral infections (colds, especially from rhinovirus), but air pollution can
      contribute to the beginning of an exacerbation. Type 1 exacerbations involve
      increased dyspnea, sputum volume, and sputum purulence; Type 2 exacerbations
      involve any two of the latter symptoms, and Type 3 exacerbations involve one of
      those symptoms combined with cough, wheeze, or symptoms of an upper respiratory
      tract infection. Exacerbations are more common than previously believed (2.5-3
      exacerbations per year); many exacerbations are treated in the community and not
      associated with hospital admission. We found that about half of exacerbations
      were unreported by the patients, despite considerable encouragement to do so,
      and, instead, were only diagnosed from patients' diary cards. COPD patients are
      accustomed to frequent symptom changes, and this may explain their tendency to
      underreport exacerbations. COPD patients tend to be anxious and depressed about
      the disease and some might not seek treatment. At the beginning of an
      exacerbation physiologic changes such as decreases in peak flow and forced
      expiratory volume in the first second (FEV(1)) are usually small and therefore
      are not useful in predicting exacerbations, but larger decreases in peak flow are
      associated with dyspnea and the presence of symptomatic upper-respiratory viral
      infection. More pronounced physiologic changes during exacerbation are related to
      longer exacerbation recovery time. Dyspnea, common colds, sore throat, and cough
      increase significantly during prodrome, indicating that respiratory viruses are
      important exacerbation triggers. However, the prodrome is relatively short and
      not useful in predicting onset. As colds are associated with longer and more
      severe exacerbations, a COPD patient who develops a cold should be considered for
      early therapy. Physiologic recovery after an exacerbation is often incomplete,
      which decreases health-related quality of life and resistance to future
      exacerbations, so it is important to identify COPD patients who suffer frequent
      exacerbations and to convince them to take precautions to minimize the risk of
      colds and other exacerbation triggers. Exacerbation frequency may vary with the
      severity of the COPD. Exacerbation frequency may or may not increase with the
      severity of the COPD. As the COPD progresses, exacerbations tend to have more
      symptoms and take longer to recover from. Twenty-five to fifty percent of COPD
      patients suffer lower airway bacteria colonization, which is related to the
      severity of COPD and cigarette smoking and which begins a cycle of epithelial
      cell damage, impaired mucociliary clearance, mucus hypersecretion, increased
      submucosal vascular leakage, and inflammatory cell infiltration. Elevated sputum
      interleukin-8 levels are associated with higher bacterial load and faster FEV(1)
      decline; the bacteria increase airway inflammation in the stable patient, which
      may accelerate disease progression. A 2-week course of oral corticosteroids is as
      beneficial as an 8-week course, with fewer adverse effects, and might extend the
      time until the next exacerbation. Antibiotics have some efficacy in treating
      exacerbations. Exacerbation frequency increases with progressive airflow
      obstruction; so patients with chronic respiratory failure are particularly
      susceptible to exacerbation.

PMID- 14651762
TI  - Key current clinical issues in alpha-1 antitrypsin deficiency.
AB  - Alpha-1 antitrypsin deficiency is a common but under-recognized condition on
      which respiratory therapists can have a large impact. A key recent development is
      the issuance of an international evidence-based standards document regarding
      diagnosis and management of individuals with alpha-1 antitrypsin deficiency. This
      report summarizes that standards document, which recommends more widespread
      testing for alpha-1 antitrypsin deficiency, in order to extend the benefits of
      diagnosis to individuals found to have alpha-1 antitrypsin deficiency. An
      important aspect of the standards document is that evidence regarding the
      clinical efficacy of intravenous alpha-1 antitrypsin augmentation therapy is
      reviewed. Though no definitive support from a randomized clinical trial is
      available, the weight of evidence favors the clinical efficacy of alpha-1
      antitrypsin augmentation therapy, at least in individuals with moderate degrees
      of established airflow obstruction. On that basis the standards document
      recommends intravenous augmentation therapy in specified clinical circumstances.

PMID- 14651763
TI  - Chronic obstructive pulmonary disease: developing comprehensive management.
AB  - The goals of managing chronic obstructive pulmonary disease include making the
      correct diagnosis, avoiding further risk (especially by smoking cessation),
      controlling symptoms (particularly dyspnea), and treating complications. Patients
      with chronic obstructive pulmonary disease can obtain substantial symptom relief
      from medications, including bronchodilators. Prescription of bronchodilators
      should be guided by the patient's degree of dyspnea, and response to initial
      therapy. In patients with severe disease and uncontrolled dyspnea, simultaneous
      use of multiple classes of bronchodilators provides additional benefit.
      Controlled investigations have found that patient adherence to prescribed
      therapies is less than optimal even in the best circumstances. Adherence barriers
      include factors related to the treatment, to the patient, and to the health care
      practitioner. Understanding these barriers and addressing patient adherence may
      improve outcomes. Health care practitioners need to develop an optimal working
      relationship with each patient and focus on their roles as educators and
      advocates for the patient's health. A collaborative self-management approach
      recognizes the patient's role in making his or her own health decisions and the
      physician's role as an educator and facilitator of the patient's health
      decisions. When multiple therapies are employed, a comprehensive management plan
      should be developed to help the patient understand and incorporate all the
      necessary treatments on an ongoing basis. Disease management programs may be
      useful in assisting health care practitioners and patients in managing chronic
      obstructive pulmonary disease.

PMID- 14651764
TI  - Smoking cessation.
AB  - Cigarette smoking is the primary cause of chronic obstructive pulmonary disease,
      and smoking cessation is the most effective means of stopping the progression of
      chronic obstructive pulmonary disease. Worldwide, approximately a billion people
      smoke cigarettes and 80% reside in low-income and middle-income countries. Though
      in the United States there has been a substantial decline in cigarette smoking
      since 1964, when the Surgeon General's report first reviewed smoking, smoking
      remains widespread in the United States today (about 23% of the population in
      2001). Nicotine is addictive, but there are now effective drugs and behavioral
      interventions to assist people to overcome the addiction. Available evidence
      shows that smoking cessation can be helped with counseling, nicotine replacement,
      and bupropion. Less-studied interventions, including hypnosis, acupuncture,
      aversive therapy, exercise, lobeline, anxiolytics, mecamylamine, opioid agonists,
      and silver acetate, have assisted some people in smoking cessation, but none of
      those interventions has strong research evidence of efficacy. To promote smoking
      cessation, physicians should discuss with their smoking patients "relevance,
      risk, rewards, roadblocks, and repetition," and with patients who are willing to
      attempt to quit, physicians should use the 5-step system of "ask, advise, assess,
      assist, and arrange." An ideal smoking cessation program is individualized,
      accounting for the reasons the person smokes, the environment in which smoking
      occurs, available resources to quit, and individual preferences about how to
      quit. The clinician should bear in mind that quitting smoking can be very
      difficult, so it is important to be patient and persistent in developing,
      implementing, and adjusting each patient's smoking-cessation program. One of the
      most effective behavioral interventions is advice from a health care
      professional; it seems not to matter whether the advice is from a doctor,
      respiratory therapist, nurse, or other clinician, so smoking cessation should be
      encouraged by multiple clinicians. However, since respiratory therapists interact
      with smokers frequently, we believe it is particularly important for respiratory
      therapists to show leadership in implementing smoking cessation.

PMID- 14651765
TI  - The guideline approach to chronic obstructive pulmonary disease: how effective?
AB  - Clinical practice guidelines are systematically developed to assist health care
      decisions in specific clinical circumstances. They first arose to improve quality
      of care by decreasing unexplained practice variation, controlling health care
      costs, fostering evidence-based decision-making, and accelerating the application
      of new advances in medical science to everyday practice. Unfortunately, multiple
      studies demonstrate incomplete and varied effectiveness of clinical practice
      guidelines in altering clinician behavior and improving patient outcomes. Efforts
      to enhance guideline effectiveness have focused on improving the methods for
      guideline development, diffusion, dissemination, and implementation. Despite
      evidence of limited effectiveness, more than 40 clinical practice guidelines
      pertaining to chronic obstructive pulmonary disease have been published since
      1985. The present article reviews those guidelines, evidence for their
      effectiveness, and approaches to improve their implementation.

PMID- 14651766
TI  - How long?

PMID- 14651770
TI  - Novel approaches to postoperative radiation therapy as part of breast-conserving
      therapy for early-stage breast cancer.
AB  - Breast-conserving therapy (BCT) consists of segmental mastectomy followed by
      postoperative radiation therapy (RT) to the whole breast. At least 6 prospective
      randomized trials have proven the equivalence of BCT to mastectomy. However, BCT
      remains underused and, most importantly, a sizable proportion of patients with
      invasive breast cancer fail to complete the recommended protocol of breast
      preservation by omitting postoperative RT. The inconvenience of complying with
      the standard 6-week radiation regimen, which includes approximately 30 daily
      visits, at least partially explains this lack of adherence. New clinical studies
      have generated preliminary evidence that more convenient, shorter radiation
      regimens might reveal equivalence to the current standard. Moreover, the
      availability of modern technology to deliver and target ionizing radiation by
      improving homogeneity of radiation dose has made it possible to safely explore
      the use of greater radiation doses per fraction. Finally, currently ongoing
      research trials will enable the identification of specific subsets of patients
      who are likely to be safely treated by partial-breast radiation (instead of
      radiation to the whole breast) with more accelerated regimens. This article
      reviews the available data and the current ongoing research on novel RT
      techniques and fractionation schedules in BCT for early-stage breast cancer.

PMID- 14651771
TI  - Optimizing the use of anthracyclines in the adjuvant treatment of early-stage
      breast cancer.
AB  - Anthracyclines have been incorporated into adjuvant chemotherapy regimens for
      breast cancer since the 1980s. A metaanalysis confirmed that regimens containing
      anthracyclines result in better disease-free and overall survival than standard
      CMF (cyclophosphamide/methotrexate/5-fluorouracil), with a proportional reduction
      of 11% in risk of death at 10 years with the addition of these agents. Dose
      escalation of doxorubicin results in outcome improvement up to a threshold dose
      beyond which no further improvement is seen. Epirubicin, with its better toxicity
      profile, can be escalated to higher doses than doxorubicin, with better outcomes
      associated with higher dose levels. Tumors expressing HER2/neu may respond better
      to anthracycline-containing regimens than to standard CMF, but this remains
      controversial. Newer regimens combining anthracyclines with taxanes may offer a
      slight additional advantage in terms of disease-free and overall survival in some
      patient populations. The scheduling of treatment is important, with recent
      results of dose-dense scheduling showing a greater survival benefit than
      conventional scheduling. Ongoing clinical trials should further define the best
      choice of anthracycline and the optimal dose and schedule of treatment.

PMID- 14651772
TI  - Risk for the development of treatment-related acute myelocytic leukemia and
      myelodysplastic syndrome among patients with breast cancer: review of the
      literature and the National Surgical Adjuvant Breast and Bowel Project
      experience.
AB  - Regimens of adjuvant chemotherapy for early-stage breast cancer commonly include
      alkylating agents and anthracyclines. These agents have been associated with
      treatment-related acute myelocytic leukemia (AML) or myelodysplastic syndrome
      (MDS). This article reviews the medical literature concerning the incidence,
      causes, and natural history of treatment-related AML/MDS, with emphasis on the
      association of these factors with alkylating agents, topoisomerase inhibitors,
      growth factors, and radiation treatment. Data from 6 completed adjuvant National
      Surgical Adjuvant Breast and Bowel Project trials that tested regimens containing
      doxorubicin and cyclophosphamide were reviewed to characterize the incidence of
      treatment-related AML/MDS. The regimens differed in cyclophosphamide intensity,
      cumulative cyclophosphamide dose, and the presence or absence of mandated
      prophylactic support with growth factor and ciprofloxacin. Rates were compared
      across regimens, by patient age, and by treatment with or without adjuvant in
      breast radiation therapy (RT). The relative risk (RR) for the development of
      treatment-related AML/MDS was greater for patients undergoing the more-intense
      regimens than for those undergoing standard AC (doxorubicin/cyclophosphamide)
      regimens (RR, 6.16; P<0.0001). Risk correlated more closely with dose intensity
      than with cumulative dose, and the data suggested that granulocyte colony
      stimulating factor (G-CSF) dose may also be independently correlated with
      increased risk. Patients who received in-breast RT experienced more secondary
      AML/MDS than those who did not (RR, 2.38; P=0.006). Patients treated with AC with
      intensified doses of cyclophosphamide requiring G-CSF support had increased rates
      of treatment-related AML/MDS, even though the incidence was slight relative to
      breast cancer relapse. In-breast RT appeared to be associated with an increased
      risk of AML/MDS.

PMID- 14651773
TI  - Worse survival in breast cancer among women with recent childbirth: results from
      a Swedish population-based register study.
AB  - This study was designed to investigate how time since childbirth affects breast
      cancer survival using unselected population-based data linking data from the
      Swedish Cancer Registry, fertility register, and population census registers. A
      total of 14,693 parous women < or =45 years of age with breast cancer were
      identified. Information on deaths was collected, and 5- and 10-year survival
      rates were calculated according to time since most recent childbirth. Mortality
      during the first 10 years of follow-up was further investigated in a Cox
      analysis, with adjustments for age at diagnosis, time period during which the
      diagnosis was made, number of children, and age at the time of the first child's
      birth. Women with diagnosis during pregnancy had a 5-year survival rate of 52.1%
      (95% CI, 41.2%-61.9%) and a 10-year survival rate of 43.9% (95% CI, 33.1%-54.2%),
      compared with survival rates of 80.0% (95% CI, 79.6%-81.4%) and 68.6% (95% CI,
      67.5%-69.7%), respectively, in women diagnosed >10 years since childbirth. In the
      multivariate model, we found that time since childbirth was associated with
      inferior survival rates in cases of diagnosis <8 years after childbirth, in which
      the lowest survival rates were seen in women with diagnosis during pregnancy in
      the first 5 years of follow-up (adjusted relative risk compared with women with
      >10 years since last childbirth, 2.6; 95% CI, 1.8-3.4). The adjusted hazard
      ratios could be described by a decreasing function of a logarithmic
      transformation of years since childbirth. We found that the time of follow-up was
      of importance, in that women with a recent pregnancy had particularly lower
      survival rates during the first 5 years after diagnosis. The mechanisms behind
      the poor survival in breast cancer for women with recent childbirth are not
      known, but we suggest that one explanation might be a lower proportion of hormone
      receptor-positive tumors.

PMID- 14651774
TI  - A phase II study of sequential docetaxel followed by doxorubicin/cyclophosphamide
      as first-line chemotherapy for metastatic breast cancer.
AB  - This phase II study assessed the activity and toxicity profile of the sequential
      administration of 3 cycles of docetaxel (100 mg/m2 every 3 weeks) followed by 3
      cycles of AC (doxorubicin/cyclophosphamide; 60/600 mg/m2 every 3 weeks) as first
      line chemotherapy in 30 patients with metastatic breast cancer. The response rate
      was 60% after docetaxel and 73% after AC. This reflected an increase in the rate
      of complete response (from 7% after docetaxel to 17% after AC). The median
      duration of response was 10.5 months, and the median time to progression was 12.6
      months. The median survival time had not been reached after a median follow-up of
      23.2 months. The sequential treatment was generally well tolerated, with grade
      3/4 neutropenia found in 20% and 14% of patients treated with docetaxel and AC,
      respectively. No cumulative myelosuppression was detected. The incidence of grade
      3/4 nonhematologic toxicities was low. The sequential administration of docetaxel
      followed by AC showed a high antitumor activity and a good safety profile. The
      hematologic toxicity found is markedly lower than that found using concomitant
      chemotherapy with the same drugs. Our results support the design of phase III
      trials that directly compare a sequential schedule with a concomitant schedule of
      docetaxel plus AC (or with doxorubicin only), focusing on the toxicity profile.

PMID- 14651775
TI  - Phase II trial of bevacizumab in combination with docetaxel in women with
      advanced breast cancer.

PMID- 14651776
TI  - Localization of IFN-gamma-activated Stat1 and IFN regulatory factors 1 and 2 in
      breast cancer cells.
AB  - The aim of the present work was to evaluate the induction and localization of
      Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-gamma
      exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20.
      Results from growth assays, Western staining, electrophoretic mobility shift
      assay (EMSA), and immunohistochemical staining were collated to test our
      hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would
      provide additional information about the functionality of the IFN-gamma signaling
      pathway in human tumor lines. EMSA results showed that in each of four cell
      lines, Stat1 expression was increased and demonstrated functional activity after
      IFN-gamma stimulation. Western and EMSA analysis showed upregulation of IRF-1 but
      not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF
      1, and IRF-2 confirmed the results and also provided novel information about the
      intracellular localization of proteins and intercellular variations in responses.
      The proportion of cells with IRF-1 stimulation and translocation was positively
      correlated with the IFN-gamma growth suppression in vitro. In conclusion, using
      four independent assays, we have demonstrated that heterogeneity in IFN-gamma
      mediated upregulation of signal transduction proteins can be detected in vitro
      and that these differences can explain distinct cellular growth effects.

PMID- 14651777
TI  - Interleukin-2 abolishes myeloid cell accumulation induced by Lewis lung
      carcinoma.
AB  - Immune aberration in cancer patients can be at least partly ascribed to an
      accumulation of immature myeloid cells and monocytes/macrophages with
      immunosuppressive functions. Mice implanted with Lewis lung carcinoma 2 (LL/2)
      cells show marked splenomegaly as the tumors progress, and this condition is
      accompanied by impaired T cell activities. We characterized the cells that
      accumulated in the spleens of LL/2 tumor-bearing mice and attempted to restore
      the normal cell population by employing interleukin-2 (IL-2). Flow cytometric
      analysis revealed that the cells expressing Mac1, B7, NK-K1, Gra-1, and MHC class
      II antigens on their surfaces drastically decreased in number when LL/2 had been
      engineered to produce IL-2. IL-2 also restored the concanavalin A (ConA)-mediated
      proliferative response and IL-2 production of the spleen cells. The in vivo
      growth of IL-2-producing tumors was significantly slower than that of parental
      LL/2 cells. Therefore, local IL-2 production may reverse systemic immune
      abnormality by stopping myeloid cell accumulation.

PMID- 14651778
TI  - Deregulated expression of interferon regulatory factor-1 in oncogene-transformed
      mouse fibroblasts.
AB  - Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that has
      been historically associated with type I IFN activation and antioncogenic
      properties. We studied IRF-1 expression and DNA-binding capacity in
      nontransformed and transformed mouse fibroblasts. A 43-kDa nuclear IRF-1 protein
      was expressed biphasically during the cell cycle in primary mouse embryo
      fibroblasts, nontransformed NIH 3T3 cells, and ras revertants. IRF-1 expression
      became constitutive in ras-transformed NIH 3T3 cells and in cells transformed by
      oncogenes ets, fes, fos, her-2/neu, met, mos, raf, or trk, suggesting that
      deregulated IRF-1 expression may be associated with loss of growth control. Lysyl
      oxidase (LO), a ras suppressor that is downregulated in ras transformants, is an
      IRF-1 target gene, but it is not stimulated by abundant IRF-1 present in
      transformants, while another IRF-1 target gene (iNOS) is transcribed. IRF-1 from
      either normal or ras-transformed cells bound to IRF elements in the IFN-beta and
      LO promoters. IRF-1 in transformants can, therefore, bind to but not
      transactivate the LO promoter, and the presence of IRF-1 is not sufficient to
      suppress ras transformation. LO expression may effect the regulated expression of
      IRF-1: a ras revertant, which was generated by stable transfection of LO cDNA,
      regained the normal biphasic IRF-1 pattern. A mainly cytoplasmic, constitutively
      expressed 46-kDa protein with immunologic identity to the 43-kDa nuclear IRF-1
      was also present in normal and transformed cells, but as it did not bind to the
      IRF elements, its function is unclear.

PMID- 14651779
TI  - Fever after zoledronic acid administration is due to increase in TNF-alpha and IL
      6.
AB  - The most common adverse event typically associated with bisphosphonate therapy is
      transient fever. The aim of this study was to define the role of the main
      cytokines of the acute-phase reaction interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) involved in the pathogenesis of zoledronic acid-induced
      fever. Eighteen consecutive cancer patients with bone metastases were treated,
      for the first time, with a single dose of 4 mg zoledronic acid infusion. They
      were prospectively evaluated for circulating TNF-alpha, interferon-gamma (IFN
      gamma), and IL-6 levels at different times, just before and 1, 2, 7, and 21 days
      after diphosphonate infusion. Clinical and standard laboratory parameters were
      recorded at the same time points. TNF-alpha circulating levels increased
      significantly 1 and 2 days after zoledronic acid infusion (respectively, p =
      0.002 and p < 0.001) and then decreased to levels similar to the basal levels. IL
      6 levels increased significantly 1 day after the infusion (p = 0.007), returning
      to values similar to the median basal values 2 days after zoledronic acid
      administration. Moreover, in patients who experienced fever, the TNF-alpha and IL
      6 increases were higher than in patients without fever. No statistically
      significant differences in IFN-gamma were identified at different time points in
      patients with and without fever. Our results show that zoledronic acid induces
      transient TNF-alpha and IL-6 increases and that these increases are higher in
      patients who have developed fever, suggesting that these cytokines could be
      responsible for fever pathogenesis. The sharp reduction in serum calcium levels
      observed in patients with fever may be related to zoledronic acid pharmacokinetic
      modifications.

PMID- 14651780
TI  - Activity of hybrid type I interferons in cells lacking Tyk2: a common region of
      IFN-alpha 8 induces a response, but IFN-alpha2/8 hybrids can behave like IFN
      beta.
AB  - Type I interferons (IFNs) are a family of pleiotropic cytokines with antiviral,
      antiproliferative, and immunomodulatory properties. The type I IFN family
      consists of 12 IFN-alpha subtypes, IFN-beta, and IFN-omega. Cells lacking the
      receptor-associated protein kinase Tyk2 (U1A) are responsive only to IFN-beta and
      partially to IFN-alpha8. We constructed a series of IFN-alpha2/alpha8 hybrids and
      mutants and identified the region within IFN-alpha8 responsible for its activity
      in Tyk2-deficient cells. The same domain mediates the interactions between IFN
      and IFN-alpha receptor (IFNAR) in Tyk2-complemented and Tyk2-deficient cells
      (U1A). The presence or absence of Tyk2 altered the inhibitory effects of anti
      IFNAR antibodies, suggesting that the IFN-alpha binding domain on IFNAR is
      altered by the presence of Tyk2. The activity of IFN-beta was not significantly
      affected by the deletion of Tyk2, and, surprisingly, one of our IFN-alpha2/alpha8
      hybrids (IFN-alpha288) behaved like IFN-beta in a number of assays that
      distinguish IFN-alphas from IFN-beta. This suggests that this hybrid mimics the
      interactions of IFN-beta with the receptor and also suggests the existence of a
      distinct binding site(s) on IFNAR for IFN-beta and some hybrid IFN-alphas.

PMID- 14651781
TI  - Function of ubiquitin-like domain of chicken 2'-5'-oligoadenylate synthetase in
      conformational stability.
AB  - 2'-5'-Oligoadenylate synthetase (OAS), an interferon (IFN) induced enzyme,
      synthesizes 2'-5'-oligoadenylate (2-5A) from ATP when activated by dsRNA. Chicken
      OAS (ChOAS) has a ubiquitin-like (UbL) domain of two consecutive sequences (UbL1
      and UbL2) at its carboxyl-terminus. The OAS gene has at least two alleles, OAS*A
      and OAS*B. OAS-A is the wild-type (wt) and OAS-B is a mutant deleted of a highly
      hydrophobic region of UbL1. To study the function of the UbL domain, enzymatic
      and physiologic properties were compared between OAS-A and OAS-B. OAS-B was more
      susceptible to trypsin than OAS-A and was converted very quickly into p38,
      deleting a greater part of the UbL domain. The p38 has the enzymatic activity to
      synthesize 2-5A. Thermal inactivation of OAS-B occurred at a lower temperature
      than that of OAS-A and p38, with loss of the ability to bind dsRNA. In contrast
      to OAS-A, the content of OAS-B in erythrocytes decreased during growth to a very
      low level. However, red blood cells (RBC) from anemic B/B chickens synthesized
      OAS-B at a high level comparable to A/A, although OAS-B levels decreased sharply
      again during maturation to erythrocytes. Thus, OAS-B carrying the mutated UbL
      domain is unstable compared with OAS-A in vitro and in vivo, and the wt UbL
      domain may contribute to the stability of the protein structure of ChOAS.

PMID- 14651783
TI  - Thyroid hormone and brain development: translating molecular mechanisms to
      population risk.

PMID- 14651784
TI  - Perspectives in the study of thyroid hormone action on brain development and
      function.
AB  - The purpose of this review is to provide an up-to-date report on the molecular
      and physiologic processes involved in the role of thyroid hormone as an
      epigenetic factor in brain maturation. We summarize the available data on the
      control of brain gene expression by thyroid hormone, the correlation between gene
      expression and physiologic effects, and the likely mechanisms of action of
      thyroid hormone on brain gene expression. In addition we propose a role for
      unliganded thyroid hormone receptors in the pathogenesis of hypothyroidism.
      Finally, we review recent data indicating that thyroid hormone receptors have an
      impact on behavior.

PMID- 14651785
TI  - Thyroid hormone and retinal development: an emerging field.
AB  - Thyroid hormone appears to play a critical, yet not fully understood, role in the
      development of the neuroretina. This review focuses on recent experiments in the
      rodent, chicken, and amphibian, with an emphasis on how the hormone and its
      receptor isoforms influence retinal cell proliferation and cell fate decisions.
      The initial results are fueling the next generation of experiments in the retina,
      which promise to provide insights into the mechanisms of thyroid hormone action
      in a wide variety of developing neural tissue.

PMID- 14651786
TI  - Polychlorinated biphenyls and thyroid status in humans: a review.
AB  - Animal studies show that exposure to polychlorinated biphenyls (PCBs) or other
      persistent organochlorine compounds can disrupt thyroid hormone homeostasis. In
      some reports dietary exposures to PCBs have also been claimed to affect
      circulating levels of thyroid hormones and thyrotropin (TSH) in humans. The aim
      of the present study was to review available epidemiologic studies within this
      field. A total of 13 studies fulfilled the inclusion criteria for the review. The
      overall impression is a lack of consistency between studies of reported
      correlations, neither are there any obvious interstudy dose-response
      associations. Thus, it cannot presently be concluded that PCB exposure has been
      convincingly shown to affect thyroid hormone homeostasis in humans. On the other
      hand, available data do not exclude such associations. It is important to be
      aware of the intrinsic limitations of the cross-sectional epidemiologic studies
      used.

PMID- 14651787
TI  - Congenital hypothyroidism: developmental outcome in relation to levothyroxine
      treatment variables.
AB  - Neonatal screening programs for congenital hypothyroidism (CH) were initiated in
      the 1970s to ensure early treatment in order to prevent mental retardation. With
      screening, developmental prognosis is considerably improved, but follow-up
      studies still report developmental delay compared to controls. To explain the
      delay, most studies have focused on effects of CH severity, supposedly caused by
      prenatal hypothyroidism. Nonoptimal treatment could also be an explanatory
      factor. Treatment guidelines have changed; now, a higher levothyroxine starting
      dose is recommended. In this review, we first summarize outcome studies in CH
      versus controls and in mild versus severe CH. Second, we report results on the
      association between levothyroxine treatment variables and developmental outcome.
      Six research groups have reported results on the association between
      levothyroxine starting dose and intelligence, and eight groups on the association
      between circulating thyroid hormones and intelligence. Most studies found a
      positive association between a high level of treatment, primarily treatment
      during the first year and later intelligence. However, negative associations
      between high-dose treatment and outcome have been reported, and the question of
      optimal treatment in relation to developmental outcome has not been answered.
      Effects of high levothyroxine dosage should be documented in samples that have
      been treated according to recent recommendations.

PMID- 14651788
TI  - Control of thyroid hormone action in the developing rat brain.
AB  - Thyroid hormones play important roles in brain development. The physiologic
      function of thyroid hormones in the developing brain is to provide a timing
      signal that leads to the induction of differentiation and maturation programs
      during precise stages of development. Inappropriate initiation of these timing
      events leads to asynchrony in developmental processes and a deleterious outcome.
      The developing brain is protected from premature thyroid hormone signaling
      through a variety of measures. Firstly, local brain levels of both thyroxine and
      triiodothyronine are controlled by ontogenically regulated patterns of production
      and metabolism. Secondly, developmentally regulated expression of nuclear
      proteins involved with the nuclear TH response apparatus control the temporal
      response of brain genes to thyroid hormone. Finally, developmental regulation of
      TH action modulating transcription factor expression also controls TH action in
      the developing brain. Together these molecular mechanisms cooperatively act to
      temporally control TH action during brain development. A description of these
      controlling mechanisms is the subject of this review.

PMID- 14651789
TI  - The thyroid hormone receptor beta gene: structure and functions in the brain and
      sensory systems.
AB  - Thyroid hormone profoundly influences the development of the vertebrate nervous
      system. The thyroid hormone receptor beta gene (Thrb) is a key mediator of many
      of these actions. The Thrb gene is complex, spanning up to 400 kb in mammals, and
      differentially expresses distinct receptor subtypes through independent tissue
      specific promoters and alternative splicing. These receptors serve a range of
      functions in the brain as well as particularly sensitive functions in the
      auditory and visual sensory systems. The Thrb gene illustrates how versatility in
      neurodevelopmental control can be achieved at the receptor level.

PMID- 14651790
TI  - Biologic variation is important for interpretation of thyroid function tests.
AB  - Large variations exist in thyrotropin (TSH) and thyroid hormones in serum. The
      components of variation include preanalytical, analytical, and biologic
      variation. This is divided into between- and within-individual variation. The
      latter consists of circadian and seasonal differences although there are
      indicators of a genetically determined starting point. The ratio of within- to
      between-individual variation describes the reliability of population-based
      reference ranges. This ratio is low for serum TSH, thyroxine (T(4)) and
      triiodothyronine (T(3)) indicating that laboratory reference ranges are
      relatively insensitive to aberrations from normality in the individual. Solutions
      are considered but reducing the analytical variation below the calculated
      analytical goals of 7%, 5% and 12% for serum T(3), T(4), and TSH does not improve
      diagnostic performance. Neither does determination of the individual set-point
      and reference range. In practice this means that population-based reference
      ranges are necessary but that it is important to recognize their limitations for
      use in individuals. Serum TSH responds with amplification to minor alterations in
      T(4) and T(3). A consistently abnormal TSH probably indicates that T(4) and T(3)
      are not normal for the individual even when inside the laboratory reference
      range. This underlines the importance of TSH in diagnosis and monitoring of
      thyroid dysfunctions. Also, it implies that subclinical thyroid disease may be
      defined in purely biochemical terms. Under critical circumstances such as
      pregnancy where normal thyroid function is of importance for fetal brain
      development, subclinical thyroid disease should be treated. Even TSH within the
      reference range may be associated with slightly abnormal thyroid function of the
      individual. The clinical importance of such small abnormalities in thyroid
      function in small children and pregnant women for brain development remains to be
      elucidated.

PMID- 14651791
TI  - Innovation and competence in an era of medical workforce flux.

PMID- 14651792
TI  - Polychromatic LED therapy in burn healing of non-diabetic and diabetic rats.
AB  - OBJECTIVE: We determined the effect of polychromatic light-emitting diodes (LED)
      in burn healing of non-diabetic and streptozotocin-induced diabetic rats.
      BACKGROUND DATA: LEDs were used as the light source for phototherapy. MATERIALS
      AND METHODS: The polychromatic LED is a cluster of 25 diodes emitting photons at
      wavelengths of 510-543, 594-599, 626-639, 640-670, and 842-879 nm with 272-mW
      output power. Age-matched, male Sprague-Dawley rats (n = 30) were used.
      Streptozotocin (70 mg/kg) was used for diabetes induction. Rat weight,
      hyperglycemia, and glycosuria were monitored for the first 3 days and weekly
      thereafter. Rats were anesthetized and shaved after 1 week of diabetes. Burn
      areas of 1.5 +/-.03 cm2 were created using a metal rod pre-heated up to 600
      degrees C that was applied for 2 sec. Diabetic and non-diabetic rats were
      randomized into the following treatment groups: control, 5, 10, 20, and 30 J/cm2.
      Light treatment commenced after burn infliction and was repeated three times per
      week. Burn areas were measured daily. RESULTS: Burn healing was impaired
      significantly during diabetes by -46.17%. Polychromatic LED treatment using 5,
      10, 20, and 30 J/cm2 incident doses influenced healing by 6.85%, 4.93%, -4.18%,
      and -5.42% in the non-diabetic rats; and 73.87%, 76.77%, 60.92%, and 48.77% in
      the diabetic rats, relative to their controls, respectively. CONCLUSION: The
      effect of polychromatic LED in non-diabetic rats was insignificant; however, it
      simulated the trend of stimulation and inhibition seen using low-level lasers.
      Significant stimulation observed in the diabetic rats demonstrated the usefulness
      of polychromatic LED in diabetic burn healing.

PMID- 14651793
TI  - Aorta and skin tissues welded by near-infrared Cr4+:YAG laser.
AB  - OBJECTIVE: The aim of our study was to explore the wavelength dependence of
      welding efficacy. Ex vivo samples of human and porcine aorta and skin tissues
      were investigated using a tunable Cr(4+):yttrium aluminum garnet (YAG) laser.
      BACKGROUND DATA: Tissue welding is possible using laser light in the NIR spectral
      range. Collagen bonding in the tissue induced by thermal, photothermal, and
      photochemical reactions-or a combination of all of these-is thought to be
      responsible for tissue welding. Laser tissue welding (LTW) has gained success in
      the laboratory using animal models. Transition from laboratory to clinical
      application requires the optimization of welding parameters. MATERIALS AND
      METHODS: A near-infrared (NIR) Cr(4+):YAG laser was used to weld ex vivo samples
      of human and porcine aorta and skin at wavelengths from 1430 to 1470 nm. Welding
      efficacy was monitored by measuring the tensile strength of the welded tissue and
      the extent of collateral tissue damage. Tensile strengths were measured using a
      digital force gauge. Changes in tissue morphology were evaluated using optical
      and scanning electron microscope (SEM). Fluorescence imaging of the welded areas
      was also used to evaluate molecular changes following tissue welding. RESULTS:
      Full-thickness tissue bonding was observed with porcine aorta samples. No
      collateral damage of the aorta samples was observed. Tissue denaturation was
      observed with human aorta, human skin, and porcine skin samples. The optimum
      tensile strength for porcine and human aorta was 1.33 +/- 0.15 and 1.13 +/- 0.27
      kg/cm2, respectively, at 1460 nm, while that for porcine and human skin was 0.94
      +/- 0.15 and 1.05 +/- 0.19 kg/cm2, respectively, achieved at 1455 nm. The weld
      strength as a function of wavelength demonstrated a correlation with the
      absorption spectrum of water. Fluorescence imaging of welded aorta and skin
      demonstrated no significant changes in collagen and elastin emission at the weld
      site. CONCLUSION: The observation that welding strength as a function of
      wavelength follows the absorption bands of water suggests that absorption of
      light by water plays a significant role in laser tissue welding.

PMID- 14651794
TI  - Effects of pulse frequency of low-level laser therapy (LLLT) on bone nodule
      formation in rat calvarial cells.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of pulse
      frequencies of low-level laser therapy (LLLT) on bone nodule formation in rat
      calvarial cells in vitro. BACKGROUND DATA: Various photo-biostimulatory effects
      of LLLT, including bone formation, were affected by some irradiation factors such
      as total energy dose, irradiation phase, laser spectrum, and power density.
      However, the effects of pulse frequencies used during laser irradiation on bone
      formation have not been elucidated. MATERIALS AND METHODS: Osteoblast-like cells
      isolated from fetal rat calvariae were irradiated once with a low-energy Ga-Al-As
      laser (830 nm, 500 mW, 0.48-3.84 J/cm2) in four different irradiation modes:
      continuous irradiation (CI), and 1-, 2-, and 8-Hz pulsed irradiation (PI-1, PI-2,
      PI-8). We then investigated the effects on cellular proliferation, bone nodule
      formation, alkaline phosphatase (ALP) activity, and ALP gene expression. RESULTS:
      Laser irradiation in all four groups significantly stimulated cellular
      proliferation, bone nodule formation, ALP activity, and ALP gene expression, as
      compared with the non-irradiation group. Notably, PI-1 and -2 irradiation
      markedly stimulated these factors, when compared with the CI and PI-8 groups, and
      PI-2 irradiation was the best approach for bone nodule formation in the present
      experimental conditions. CONCLUSION: Since low-frequency pulsed laser irradiation
      significantly stimulates bone formation in vitro, it is most likely that the
      pulse frequency of LLLT an important factor affecting biological responses in
      bone formation.

PMID- 14651795
TI  - Cleaning of the root canal using Nd:YAP laser and its effect on the mineral
      content of the dentin.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of root canal
      cleanliness with and without Nd:YAP laser and to assess the effect of the laser
      on the mineral content of the dentin. BACKGROUND DATA: A high degree of
      cleanliness of the canal when using the Nd:YAG laser has been shown while the
      laser is in contact with the canal wall. A new Nd:YAP laser has been studied
      recently, which is considered to be superior to the Nd:YAG with regard to
      antibactericidal ability due to its 1.34 micro m wavelength, which is in the
      infra-red range. This wavelength is absorbed better in water than that of Nd:YAG.
      MATERIALS AND METHODS: Fourteen extracted single rooted premplars were divided
      into two groups. In group 1, canals were cleaned, instrumented, and shaped with K
      files. In group 2, initial preparation was done using K files and completed with
      a Nd:YAP laser. Teeth were then split longitudinally and submitted to scanning
      electron microscopy. RESULTS: The cleanliness of the laser-treated teeth was
      significantly greater than teeth treated with K files alone (p < 0.05). No
      difference in Ca and P content was detected when the use of K files was compared
      to the use of laser. CONCLUSION: It appears that the Nd:YAP laser improves the
      cleanliness of the root canal. However, since the Nd:YAP laser serves as an
      addition to K files, its clinical value for replacing conventional root canal
      instrumentation remains to be determined.

PMID- 14651797
TI  - Effect of the clinical application of the GaAlAs laser in the treatment of
      dentine hypersensitivity.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of the
      clinical use of the gallium-aluminum-arsenium (GaAlAs) laser at the maximum and
      minimum energies recommended by the manufacturer for the treatment of dentine
      hypersensitivity. BACKGROUND DATA: Dentine hypersensitivity (DH) is a response to
      a stimulus that would not usually cause pain in a healthy tooth. It is
      characterized by sharp pain of short duration from the denuded dentin. Its
      etiology is unknown. The dentin only begins to show sensitivity when exposed to
      the buccal environment. This exposure can result after removal of the enamel
      and/or dental cement, or after root denudation. Different treatments are proposed
      for this disorder. MATERIALS AND METHODS: In this study, 25 patients, with a
      total number of 106 cases of DH, were treated with GaAlAs low-level laser therapy
      (LLLT). 65% of the teeth were premolars; 14% were incisors and molars; 6.6% were
      canines. The teeth were irradiated with 3 and 5 J/cm2 for up to six sessions,
      with an interval of 72 h between each application, and they were evaluated
      initially, after each application, and at 15 and 60 days follow-up post
      treatment. RESULTS: The treatment was effective in 86.53% and 88.88% of the
      irradiated teeth, respectively, with the minimum and maximum energy recommended
      by the manufacturer. There was a statistically significant difference between DH
      and after a follow-up of 60 days for both groups. The difference among the energy
      maximum and minimum was not significant. CONCLUSION: The GaAlAs low-level laser
      was effective in reducing initial DH. A significant difference was found between
      initial values of hypersensitivity and after 60 days follow-up post-treatment. No
      significant difference was found between minimum (3 J/cm2) and maximum (5 J/cm2)
      applied energy.

PMID- 14651796
TI  - Effects of low-level laser therapy (LLLT) of 810 nm upon in vitro growth of
      bacteria: relevance of irradiance and radiant exposure.
AB  - OBJECTIVE: The aim of this study was to investigate the irradiance-dependency of
      low-level laser therapy (LLLT) effects on bacterial growth. BACKGROUND: LLLT is
      applied to open wounds to improve healing; however, its effect on wound bacteria
      is not well understood. MATERIALS AND METHODS: Escherichia coli, Pseudomonas
      aeruginosa, and Staphylococcus aureus were irradiated using a wavelength of 810
      nm at irradiances of 0.015 W/cm2 (0-50 J/cm2) and 0.03 W/cm2 (0-80 J/cm2).
      Bacteria were counted after 20 h of incubation. RESULTS: LLLT effects varied
      significantly with species. P.aeruginosa growth decreased overall dependent on an
      interaction of irradiance and radiant exposure; greatest inhibition was produced
      using high irradiance delivering radiant exposures in the range of 1-20 J/cm2 (p
      = 0.001-0.04). In contrast, E. coli growth increased overall (p = 0.01),
      regardless of irradiance; greatest effects were produced using low radiant
      exposures (1-20 J/cm2). There was a main effect for irradiance (p = 0.03) on S.
      aureus growth; however, growth was not different compared with controls.
      Additional analysis showed that there were differences in growth of P.aeruginosa
      when comparing samples that were matched by exposure times (66, 329, 658, 1316,
      1974, and 2632 sec) rather than radiant exposure; this suggests that irradiance
      rather than exposure time was the significant factor in P. aeruginosa inhibition.
      CONCLUSION: These findings have immediate relevancy in the use of LLLT for
      infected wounds. Exposure to 810-nm irradiation (0.03 W/cm2) could potentially
      benefit wounds infected with P. aeruginosa. However, increased E. coli growth
      could further delay recovery.

PMID- 14651798
TI  - Parotid surgery using Nd:YAG laser contact tips: clinical assessment of
      perioperative facial nerve function.
AB  - OBJECTIVE: The objective of this paper is to review 51 consecutive contact Nd:YAG
      laser parotidectomies to determine perioperative outcomes and complications
      related to the facial nerve and the use of the laser tips. BACKGROUND DATA:
      Parotid surgery is mostly performed with scalpel or scissors, techniques that may
      put the facial nerve at risk for injury due to brisk bleeding and imprecise
      dissection. Even though previous experiences with Nd:YAG lasers in surgery had
      raised concerns of energy dispersion, the contact sapphire tips used in this
      series allowed accurate precise dissection and hemostasis, limiting
      complications. MATERIALS AND METHODS: Close facial nerve dissection was done at 8
      12 watts, for an average total of 8,000-12,000 joules per case. RESULTS: No
      significant or permanent facial nerve complications resulted from the use of the
      laser tips, except for expected transient and reversible postoperative
      ipsilateral marginal mandibular nerve paresis observed in 43% of the patients
      less than the generally quoted 50% expected after uneventful lateral lobe
      parotidectomy. CONCLUSION: This review concludes that the contact Nd:YAG laser
      may offer significant technical and safety advantages, and no direct associated
      complications in the dissection and preservation of the facial nerve in
      parotidectomy.

PMID- 14651799
TI  - Effect of 830-nm laser light on the repair of bone defects grafted with inorganic
      bovine bone and decalcified cortical osseus membrane.
AB  - OBJECTIVE: The aim of this study was to histologically assess the effect of low
      level laser therapy (LLLT) (lambda830 nm) on the repair of standardized bone
      defects of the femur of Wistar albinus rats grafted with inorganic bovine bone
      and associated (or not) with decalcified bovine cortical bone membrane.
      BACKGROUND DATA: Bone loss may be a result of pathology, trauma, or surgical
      procedure. Extensive studies on the process of bone repair have been undertaken,
      and several techniques for the correction of bone defects have been proposed.
      Amongst them is the use of several types of grafts, the use of membranes, and the
      combination of both techniques. There is evidence in the literature of the
      positive effect of LLLT on the healing of soft tissue wounds. However, its effect
      on bone healing is not completely understood. MATERIALS AND METHODS: Five
      randomized groups were studied: group I (control); group IIA (Gen-ox); group IIB
      (Gen-ox + LLLT); group IIIA (Gen-ox + Gen-derm); and group IIIB (Gen-ox + Gen
      derm + LLLT). Bone defects were created at the femur and were treated according
      to the group. The animals of irradiated groups were irradiated every 48 h for 15
      days; the first irradiation was performed immediately after the procedure. The
      animals were irradiated transcutaneuosly at four points around the defect. At
      each point, a dose of 4 J/cm2 was given (phi approximately equal to 0.6 mm, 40
      mW), and the total dose per session was 16 J/cm2. The animals were humanely
      killed at 15, 21, and 30 days after surgery. The specimens were routinely
      processed to wax, serially cut, stained with H&E and Picrosirius stains, and
      analyzed under light microscopy. RESULTS: The results showed more advanced repair
      of the irradiated groups when compared to the non-irradiated ones. The repair of
      the irradiated group was characterized by both increased bone formation and on
      the amount of collagen fibers around the graft within the cavity, as early as the
      15th day after surgery, considering the osteoconductive capacity of the Gen-ox
      and the increment of the cortical repair in specimens with Gen-derm membrane.
      CONCLUSION: It is concluded that LLLT had a positive effect on the repair of bone
      defect by graft associated or not with the use of biological membrane.

PMID- 14651800
TI  - Comparative study of carious dentin removal by Er,Cr:YSGG laser and Carisolv.
AB  - OBJECTIVE: The present study aimed to compare carious dentin removal by air
      turbine, Carisolv and erbium,chromium:yttrium,scandium,gallium,garnet
      (Er,Cr:YSGG) laser, and examine morphological changes before and after these
      caries removal techniques under light microscopy and scanning electron microscopy
      (SEM). BACKGROUND DATA: Although there have been numerous studies on removing
      caries by Er,Cr:YSGG laser, none has compared Er,Cr:YSGG laser and Carisolv, or
      reported on the usage of DIAGNOdent as a diagnostic tool particularly for
      advanced caries in in vitro experiments. MATERIALS AND METHODS: Sixty extracted
      human teeth diagnosed as advanced caries were divided into three groups based on
      the treatment received, namely air turbine, Carisolv, and Er,Cr:YSGG laser
      groups. Each group was sub-divided into two in order to examine the results with
      or without finishing using nylon brush, 15% ethylene diamine tetraacetic acid
      (EDTA) or low-power laser, respectively. After evaluation by DIAGNOdent,
      specimens were observed under light microscopy or SEM. RESULTS: Light microscopic
      observations varied considerably in the three treatment groups. SEM revealed that
      the surfaces treated by air turbine were very smooth, but with substantial
      debris. The Carisolv group exhibited a very rough surface with a thick smear
      layer, while the Er,Cr:YSGG group demonstrated smooth undulations with little
      smear layer and debris. Among the finishing techniques, the laser group
      demonstrated the best efficiency. DIAGNOdent scores supported the results of
      light microscopy. CONCLUSION: These results suggest that caries removal by
      Er,Cr:YSGG laser is very effective even without finishing and DIAGNOdent is
      useful for diagnosing advanced caries in in vitro experiments.

PMID- 14651803
TI  - Profile of gene expression in the subventricular zone after traumatic brain
      injury.
AB  - Neural stem cells, which reside in the subventricular zone (SVZ) and dentate
      gyrus (DG) of adult mammals, give rise to new neurons throughout life. However,
      these neural stem cells do not appear to contribute to regeneration in the
      damaged central nervous system. Following traumatic brain injury (TBI) in adult
      rats, the number of proliferating cells labeled with bromodeoxyuridine (BrdU) is
      significantly increased in the bilateral SVZ and DG; however, these proliferating
      cells do not contribute to effective regeneration in the damaged area. To gain
      insight into the molecular mechanisms of these biological actions, changes in
      gene expression in the SVZ after brain trauma were examined by cDNA microarray.
      Of 9,596 genes screened, 97 were upregulated and 204 were downregulated.
      Classifying these genes according to their function suggests that TBI affects a
      broad range of cellular functions. The validity of the data was confirmed by RT
      PCR. The expression of some genes localized in the SVZ was confirmed by in situ
      hybridization. This combined strategy is effective for comprehensive analysis of
      the pathophysiological changes in the SVZ after brain injury and should
      contribute to the understanding of the molecular events that occur after injury.
      In the future, this may enable regeneration of the damaged central nervous
      system.

PMID- 14651804
TI  - Age-dependent changes in material properties of the brain and braincase of the
      rat.
AB  - Clinical and biomechanical evidence indicates that mechanisms and pathology of
      head injury in infants and young children may be different from those in adults.
      Biomechanical computer-based modeling, which can be used to provide insight into
      the thresholds for traumatic tissue injury, requires data on material properties
      of the brain, skull, and sutures that are specific for the pediatric population.
      In this study, brain material properties were determined for rats at postnatal
      days (PND) 13, 17, 43, and 90, and skull/suture composite (braincase) properties
      were determined at PND 13, 17, and 43. Controlled 1 mm indentation of a force
      probe into the brain was used to measure naive, non-preconditioned (NPC) and
      preconditioned (PC) instantaneous (G(i)) and long-term (G( infinity )) shear
      moduli of brain tissue both in situ and in vitro. Brains at 13 and 17 PND
      exhibited statistically indistinguishable shear moduli, as did brains at 43 and
      90 PND. However, the immature (average of 13 and 17 PND) rat brain (G(i) = 3336
      Pa NPC, 1754 Pa PC; G( infinity )= 786 Pa NPC, 626 Pa PC) was significantly
      stiffer (p < 0.05) than the mature (average of 43 and 90 PND) brains (G(i) = 1721
      Pa NPC, 1232 Pa PC; G( infinity ) = 508 Pa NPC, 398 Pa PC). A "reverse
      engineering" finite element model approach, which simulated the indentation of
      the force probe into the intact braincase, was used to estimate the effective
      elastic moduli of the braincase. Although the skull of older rats was
      significantly thicker than that of the younger rats, there was no significant age
      dependent change in the effective elastic modulus of the braincase (average value
      = 6.3 MPa). Thus, the increase in structural rigidity of the braincase with age
      (up to 43 PND) was due to an increase in skull thickness rather than stiffening
      of the tissue. These observations of a stiffer brain and more compliant braincase
      in the immature rat compared with the adult rat will aid in the development of
      age-specific experimental models and in computational head injury simulations.
      Specifically, these results will assist in the selection of forces to induce
      comparable mechanical stresses, strains and consequent injury profiles in brain
      tissues of immature and adult animals.

PMID- 14651805
TI  - Mild hypothermia inhibits exogenous glutamate-induced increases in nitric oxide
      synthesis.
AB  - The purpose of this study was to investigate changes in nitric oxide (NO)
      synthesis induced by exogenous glutamate perfusion into the cerebral cortex, and
      the effects of mild hypothermia on this glutamate-induced NO synthesis. Glutamate
      induced cortical lesions were produced by perfusion of 0.5 M glutamate solution
      via a microdialysis probe, and the extracellular concentrations of NO end
      products (nitrite and nitrate) were measured by microdialysis in normothermic (37
      degrees C) and hypothermic (32 degrees C) rats. The levels of NO end-products in
      the normothermia group were elevated markedly by glutamate perfusion, and this
      change was completely attenuated by the induction of hypothermia. The glutamate
      induced increases were also attenuated markedly by both Nomega-nitro-L-arginine
      methyl ester (L-NAME) and 7-nitroindazole (7-NI). These results suggest that the
      perfusion of exogenous glutamate into the cortex induces NO synthesis, that is
      derived primarily from the activity of neuronal NO synthase. These results also
      demonstrate that hypothermia prevents this glutamate-induced increase in NO,
      suggesting that the protection afforded by the hypothermic condition is most
      likely linked to its inhibition of the glutamate-induced NO synthesis.

PMID- 14651806
TI  - Treatment with vitamin B3 improves functional recovery and reduces GFAP
      expression following traumatic brain injury in rats.
AB  - Previous studies have shown that administration of vitamin B(3) (B(3)) in animal
      models of ischemia significantly reduced the size of infarction and improved
      functional recovery. The present study evaluated the effect of administration of
      B(3) on recovery of function following traumatic brain injury (TBI),
      incorporating the bilateral medial frontal cortex contusion injury model. Groups
      of rats were assigned to B(3) (500 mg/kg) or saline (1.0 ml/kg) treatment
      conditions and received contusion injuries or sham surgeries. Drug treatment was
      administered 15 min and 24 h following injury. Rats were examined on a variety of
      tests to measure sensorimotor performance (bilateral tactile adhesive removal),
      skilled forelimb use (staircase test), and cognitive ability (reference and
      working memory) in the Morris Water Maze. Administration of B(3) following injury
      significantly reduced the behavioral impairments observed on the bilateral
      tactile removal test, but not on skilled forelimb use. The acquisition of
      reference and working memory tests were also significantly improved compared to
      saline-treated rats. Examination of the brains revealed that administration of
      B(3) significantly reduced the size of the lesion compared to treatment with
      saline. In addition, examination of glial fibrillary acidic protein (GFAP)
      expression around the lesion revealed that B(3) significantly reduced the number
      of GFAP(+) astrocytes. These results indicate that B(3) administration
      significantly improved behavioral outcome following injury, reduced the size of
      the lesion, and reduced the expression of GFAP. The current findings suggest that
      B(3) may have therapeutic potential for the treatment of TBI.

PMID- 14651807
TI  - Apoptosis of spinal cord neurons by preventing depletion nicotine attenuates
      arachidonic acid-induced of neurotrophic factors.
AB  - Increased levels of free fatty acids and, in particular, arachidonic acid can
      lead to induction of apoptosis of spinal cord neurons. Because of the importance
      of neurotrophic factors in cell survival and death, mRNA and protein levels of
      brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF
      2) were studied in cultured spinal cord neurons treated with arachidonic acid. In
      addition, the present study focused on the effects of nicotine and neuronal
      nicotinic acetylcholine receptors (nAChRs) on these processes. A 2-h exposure to
      arachidonic acid markedly diminished expression of BDNF and FGF-2. These effects
      were fully prevented by pretreatment with 10 microM nicotine. Mecamylamine (a non
      specific antagonist of nAChRs) and alpha-bungarotoxin (a specific antagonist of
      the nAChRalpha7) completely inhibited nicotine-mediated protection against
      arachidonic acid-induced alterations of BDNF and FGF-2. In addition, nicotine,
      BDNF and FGF-2 fully protected against arachidonic acid-induced apoptosis of
      spinal cord neurons. BDNF and FGF-2 were effective in prevention of apoptotic
      cell death even when applied 2 h after the beginning of arachidonic acid
      treatment. These results suggest that arachidonic acid can induce apoptosis of
      spinal cord neurons by depletion of neurotrophic factors and that nicotine can
      protect against these effects through the nAChRalpha7-mediated pathway.

PMID- 14651808
TI  - Leukemia inhibitory factor promotes recovery of locomotor function following
      spinal cord injury in the mouse.
AB  - We describe an easy, minimal, rapid, and reproducible model of mouse spinal cord
      injury (SCI) that results in permanent paralysis involving one hind limb. We used
      this model to evaluate whether the paralysis can be prevented using two known
      neuroprotective drugs, namely leukemia inhibitory factor (LIF) and minocycline
      (MIN). Mice in the control vehicle (VEH) and MIN groups with SCI had negligible
      recovery of locomotor behavior. In contrast, the LIF groups showed a
      statistically significant improvement in locomotor behavior. Maximal recovery was
      observed when LIF was administered 2, 8, and 24 h after lesion, while no
      significant recovery was observed when LIF treatment commenced 1 week after the
      lesion. Unbiased stereological estimates revealed significantly higher numbers of
      myelinated axons below the lesion in the maximal recovery LIF groups. We conclude
      that LIF may be a useful treatment for recovery from paralysis after SCI.

PMID- 14651809
TI  - Fluoro-jade B stains quiescent and reactive astrocytes in the rodent spinal cord.
AB  - In an attempt to label dying neurons in the injured spinal cord, we used the
      novel fluorescein derivative Fluoro-Jade B, which has been reported to
      specifically label dead or dying neurons in the brain. Rats and mice were
      subjected to a moderate level of spinal cord injury using an IH impact device and
      sacrificed at 1, 2, 4, 7, 14, and 21 days post injury. Spinal cord tissue was
      processed for Fluoro-Jade B histochemistry and included sections throughout the
      injured region of the cord. No Fluoro-Jade positive neurons were observed in
      sections from any time point postinjury at any level of the spinal cord. Instead,
      Fluoro-Jade labeled astrocytes in uninjured control animals and injured animals.
      The specificity of astrocytic staining was confirmed by co-localizaton of Fluoro
      Jade with glial fibrillary acidic protein. We also subjected a group of rats to a
      sequential cortical contusion injury and spinal cord injury. Sections from these
      animals showed numerous Fluoro-Jade positive neurons in the hippocampal formation
      and thalamus underlying the cortical contusion; however, the staining pattern in
      the spinal cord was identical to those animals that had received spinal cord
      injury alone.

PMID- 14651810
TI  - Modulation of stretch-induced enhancement of neuronal NMDA receptor current by
      mGluR1 depends upon presence of glia.
AB  - Stretching of cultured neurons has been used to model diffuse axonal injury
      associated with brain trauma. N-Methyl-D-aspartate receptor (NMDAR) activation
      and group I metabotropic glutamate receptors (mGluRs) are implicated in the
      pathophysiology of such injury. Here we detail the effects of culture condition
      and mGluR1 modulation on stretch-enhanced NMDA receptor activity, and show the
      presence of mGluR1 in addition to mGluR5 in glia. In cortical neurons grown in
      the absence (PN) or presence (NG) of a glial monolayer, stretch injury (5.7 mm)
      enhances NMDAR activity by increasing maximal NMDAR current, decreasing the
      voltage-dependent Mg(2+) block, and altering the kinetic behavior of these
      receptors. In PN cultures, activation of mGluR1 increases stretch-enhanced NMDAR
      activity, whereas in NG cultures, such activity is reduced. In contrast,
      inhibition of mGluR1 in PN cultures limits stretch-enhanced NMDAR activity,
      whereas in NG cultures activity is increased. MGluR1 modulate stretch-enhanced
      NMDAR activity through multiple mechanisms including: altering peak or steady
      state current, affecting Mg(2+) blockade of the NMDAR, or by changing NMDAR
      kinetics. The presence of glia significantly alters the nature of mGluR1-mediated
      modulation of NMDAR activity and stretch-induced injury. Together these data
      indicate a significant neuronal/glial interaction between glial mGluR1 and
      neuronal NMDA receptor activity.

PMID- 14651811
TI  - Restriction of axonal retraction and promotion of axonal regeneration by
      chronically injured neurons after intraspinal treatment with glial cell line
      derived neurotrophic factor (GDNF).
AB  - The response of supraspinal neurons to acute or delayed treatment with GDNF
      following a spinal cord injury was examined. A cervical level 3 hemisection
      lesion cavity was created by tissue aspiration in adult, female rats. In one
      experiment gel foam saturated with GDNF was placed into the lesion cavity
      immediately after injury to determine if the extent of axonal retraction was
      affected by neurotrophic factor treatment. One week prior to sacrifice animals
      received a microinjection of biotinylated dextran amine (BDA) into the red
      nucleus and reticular formation to label descending spinal pathways by
      anterograde transport mechanisms. Animals were sacrificed 1 or 4 weeks after
      injury and treatment with GDNF. The terminal end of injured BDA-labeled
      rubrospinal and reticulospinal tract axons was identified and the distance from
      the lesion was measured. In comparison to PBS-treated animals, GDNF-treatment
      resulted in a significant decrease in the extent of axonal retraction of both
      rubrospinal and reticulospinal tract axons at 1 week after spinal cord injury for
      both tracts. At 4 weeks after injury the mean distance from the lesion was less
      than 240 microm following GDNF-treatment for both tracts, compared to over 480
      microm following PBS-treatment. In the second experiment injured supraspinal
      neurons were labeled by retrograde transport of True Blue that had been placed
      into the lesion cavity. One month later scar tissue was removed from the cavity
      by aspiration to enlarge the cavity by approximately 500 microm in a rostral
      direction. GDNF-saturated gel foam was placed into the cavity for 60 min prior to
      apposition of an autologous peripheral nerve (PN) graft to the rostral cavity
      wall. One month later Nuclear Yellow was applied to the distal end of the PN
      graft and animals were sacrificed after 2 days. The number of supraspinal neurons
      containing both True Blue and Nuclear Yellow was counted as a measure of axonal
      regeneration by chronically injured neurons. There was a seven-fold increase in
      the number of regenerating neurons after GDNF-treatment, with the majority (65%)
      of dual-labeled neurons located within the reticular formation. These results
      indicate that GDNF has neuroprotective effects when provided acutely after injury
      and promotes axonal regeneration when provided in a chronic injury situation.

PMID- 14651812
TI  - Training on a visual task improves the outcome of optic nerve regeneration.
AB  - Optic nerve regeneration in a lizard, Ctenophorus ornatus, is dysfunctional
      despite survival of most retinal ganglion cells and axon regeneration to the
      optic tectum. The regenerated retino-tectal projection at 6 months has crude
      topography but by 1 year is disordered; visually-elicited behavior is absent via
      the experimental eye. Here, we assess the influence of training on the outcome of
      optic nerve regeneration. Lizards were trained to catch prey presented within the
      monocular field of either eye. One optic nerve was then severed and visual
      stimulation resumed throughout regeneration. In the trained group, presentation
      was restricted to the eye undergoing optic nerve regeneration; for the untrained
      group, the unoperated eye was stimulated. Pupil responses returned in trained but
      not in untrained animals. At 1 year, trained animals oriented to and captured
      prey; untrained animals demonstrated minimal orienting and failed to capture
      prey. Regenerated retino-tectal projections were topographic in the trained but
      not in the untrained group as assessed by in vitro electrophysiological recording
      and by carbocyanine dye tracing. In vitro electrophysiological recording during
      application of neurotransmitter antagonists to the tectum revealed that the level
      of GABAergic inhibition was modest in trained animals but elevated in the
      untrained group; responses were mainly AMPA-mediated in both groups. We conclude
      that training improves the behavioral outcome of regeneration, presumably by
      stabilizing and refining the transient retino-tectal map and preventing a build
      up of tectal inhibition. The results suggest that for successful central nerve
      regeneration to occur in mammals, it may be necessary to introduce training to
      complement procedures stimulating axon regeneration.

PMID- 14651813
TI  - [Prevalence of latex-related sensitization in health care workers].
AB  - BACKGROUND AND OBJECTIVE: Latex exposure at work has been related to
      sensitization in health care workers. The aim of the present study was to
      determine the prevalence of this sensitization in health care workers and its
      risk factors. PATIENTS AND METHOD: The occupation, prevalence of latex-related
      symptoms and sensitization was determined in a sample of health care workers by
      questionnaire and skin testing. RESULTS: 461 subjects were studied during a year.
      30.2% of them reported dermatitis symptoms, 23.2% rhinitis, 12.6% urticaria-like
      rashes, and 5.6% reported asthmatic symptoms. 17.6% of workers reported symptoms
      when using latex gloves and 5% after the contact or ingestion of tropical fruits.
      Sensitization to latex was indentified in 12 workers (2.6%, CI95% 1.2-4.0).
      Dermatitis, urticaria-like rashes, rhinitis and asthmatic symptoms upon exposure
      to latex products and/or tropical fruits were all significantly more prevalent in
      sensitized subjects. In the logistic regression analysis, dermatitis, urticaria
      like rashes, and asthmatic symptoms after the ingestion of tropical fruits were
      related to latex sensitization. CONCLUSIONS: The prevalence of sensitization to
      latex in health workers is nearly 3% and it must be suspected in subjects
      reporting symptoms when using latex gloves or after the ingestion of tropical
      fruits.

PMID- 14651814
TI  - [Short-term relationship between air pollution and mortality in 13 Spanish
      cities].
AB  - BACKGROUND AND OBJECTIVE: EMECAM is a collaborative project that seeks to
      evaluate the short-term effects of air pollution on mortality in Spain. MATERIAL
      AND METHOD: We collected data for air pollutants (particles and gases), daily
      mortality (total except external, cardiovascular and respiratory causes) and co
      variables (temperature, humidity, influenza and calendar variables) in 13 Spanish
      cities. The magnitude of the association in every city was estimated using GAM
      under a Poisson distribution. Combined estimates for each cause and pollutant
      were obtained under 'fixed effects' and 'random effects'models. RESULTS: An
      increase of 10 (g/m3 in the levels of the average of the concurrent and one day
      lag for black smoke was associated with a 0.8% (CI: 0.4-1.1) increase in
      mortality. The same increase in the concentration of SO2 was associated with a
      0.5% (CI: 0.1-1.0) increase in daily deaths, and a 0.6% (CI: 0.3-0.8) increase in
      the case of NO2. An increase of 1 mg/m3 in the levels of CO was associated with
      an increase of 1.5% (CI: 0.5-2.6) in daily deaths. CONCLUSIONS: There is a short
      term association between increases of daily levels of air pollutants and the
      number of daily deaths in Spanish cities.

PMID- 14651815
TI  - [Effect of statistical review on manuscript quality in Medicina Clinica
      (Barcelona): a randomized study].
AB  - BACKGROUND AND OBJECTIVE: The statistical review of biomedical articles should
      result in an improved quality. The objective of this study was to compare the
      effects of clinical review and joint clinical and statistical review on
      manuscript quality, in articles submitted to Medicina Clinica (Barcelona), a
      Spanish weekly journal of internal medicine. METHOD: Original papers arriving
      between May 2000 and February 2001 were randomized either to a clinical review
      group or a clinical and statistical review group. Two evaluators, blinded to the
      paper's group, assessed the quality improvement in both groups, from submission
      to publication using a modified version ot the Goodman et al. scale. The protocol
      required that final versions arrived before the end of May 2001. RESULTS: Final
      sample size was 43 manuscripts, evaluated before and after peer review. On the
      intention to treat analysis, the estimated effect of statistical review was 1.35
      (95% CI: -0.45 to 3.16) positive, but not statistically significant. The analysis
      of the reviewers' comments revealed some protocol deviations. Taking into account
      the spontaneous inclusion of statistical experts in the clinical group, the
      estimated effect was statistically significant, with a confidence interval of 0.3
      to 3.7. CONCLUSION: The inclusion of a statistical expert in the peer review
      process improves manuscript quality, although in the intention to treat analysis
      the improvement was not statistically significant.

PMID- 14651818
TI  - [Prevalence of hepatitis B virus infection and needs of vaccination in high risk
      populations].
AB  - BACKGROUND AND OBJECTIVE: We aimed to evaluate the serological status of
      hepatitis B virus (HBV) and the vaccination's needs among high risk populations.
      PATIENTS AND METHOD: Cross sectional study of subjects first attending a HIV
      diagnosis clinic in Madrid during 2000-2002. Patients who had not been vaccinated
      for HBV were classified according to the serological markers as active infection
      (HBsAg+), past infection (anti-HBc+ and HBsAg) or susceptible (anti-HBc).
      RESULTS: A total of 7,827 patients were analyzed: 5.2% injecting drug users, 21%
      homosexual men, 38% female sex workers, and 34% subjects with other heterosexual
      risks. 50% were from countries other than Spain. HIV prevalence was 4.1%. 10.4%
      had completed or initiated the vaccination. The prevalence of HBsAg was 1.2% and
      it was associated with age over 30 years and an origin country in Africa or
      eastern Europe. 76% were susceptible to HBV and this status was independently
      associated with male sex, age lower than 30 years, heterosexual risk, Spaniard or
      Latin American origin, and HIV seronegative. CONCLUSIONS: Vaccination should be
      intensified in health care settings commonly attended by these population groups.

PMID- 14651817
TI  - [Celecoxib in NSAID-induced cutaneous and respiratory adverse reactions].
AB  - BACKGROUND AND OBJECTIVE: Inhibition of COX-1 appears to be a key event in most
      non-steroidal anti-inflammatory drugs (NSAIDs)-induced adverse reactions. We
      evaluated celecoxib tolerance, a highly specific COX-2 inhibitor, in NSAIDs
      sensitive patients. PATIENTS AND METHOD: Intolerant patients were challenged in a
      single-blind study with placebo and celecoxib (increasing doses up to 400 mg).
      RESULTS: We included 59 patients (41 women): 34 with urticaria with or without
      angiodema, 21 with bronchospasm, and 4 with urticaria and bronchospasm. Only two
      patients on celecoxib developed urticaria (3.4%). CONCLUSIONS: Celecoxib is well
      tolerated by most NSAIDs-intolerant patients and can be a safe alternative when
      analgesic or antiinflammatory therapy is indicated.

PMID- 14651819
TI  - [Severe acute respiratory syndrome: will it come back?].

PMID- 14651820
TI  - [Influenza vaccination: only advantages?].

PMID- 14651821
TI  - [Occult values management in the clinical relationship].

PMID- 14651822
TI  - [Combined cardiorenal failure: a rapidly expanding clinical entity].
AB  - The cardiovascular diseases represent the chief cause of morbidity and mortality
      in Spain. The development of renal insufficiency has a definite prognostic value
      and modifies therapeutic options. Cardio-renal insufficiency (IC-R) is a
      differentiated entity, underestimated in our population, in which both cardiac
      and renal failure coexist. Patients with IC-R are genuine survivors of the
      application of diverse technologies and have a different hemodynamic and
      hydrosaline balance compared to that seen in patients with isolated cardiac or
      renal insufficiency. Early diagnosis and careful follow-up, both in hospital and
      at ambulatory level, along with a specific management, determine the prognosis of
      this entity. A key aspect in the control of these patients resides in the
      preservation of a delicate fluid balance, which is always individualized and
      personalized. This type of approach requires a particular type of training and
      mental attitude by healthcare professionals, with an integrated view of the
      multifactorial nature of IC-R. The design of a plan structured according to
      objectives and the full understanding of the individual equilibrium constitute
      the keystone in the management of IC-R. The present review, which is based on
      traditional concepts updated under a practical view, is aimed to call attention
      on a rapidly expanding clinical entitiy.

PMID- 14651824
TI  - [The science of triage].

PMID- 14651823
TI  - [Serum S 100 beta in hepatic encephalopathy].

PMID- 14651826
TI  - [Theme networks in cooperative research].

PMID- 14651827
TI  - [Validity in a community (with outside verification) of primary prevention
      studies on hypercholesterolemia].
AB  - OBJECTIVES: The main objective of this study was to determine the degree of
      similarity between large primary prevention trials of hypercholesterolemia and
      our population of patients with dyslipidemia, in order to evaluate the external
      validity of these studies and their applicability to the general population.
      DESIGN: Descriptive retrospective study. SETTING: Tafalla Health Center in
      Navarra (Northern Spain), serving a population of 11 500
      inhabitants.Participants. All patients older than 18 years assigned to our health
      center who had dyslipidemia with no antecedents of ischemic heart disease.
      RESULTS: The percentage of patients in our sample who satisfied the inclusion
      criteria used in large clinical trials ranged from 2.4% to 46%, depending on the
      study: AFCAPS/TexCAPS 1998, 46.2%; HPS 2002, 46.1%; WOSCOPS 1995, 10.9%; HHS
      1987, 10.6%; LRC-CPPT 1984, 2.4%. CONCLUSIONS: Many of our patients (54%-97%)
      with dyslipidemia would not have been eligible for inclusion in earlier studies
      of hyperlipidemia and primary prevention. The external validity (applicability to
      the general population) of these studies is questionable. Decision-making in
      clinical practice for the primary prevention of hypercholesterolemia should be
      based on the risk/benefit ratio of pharmacological treatment.

PMID- 14651828
TI  - [Commentary: External validity of studies on Primary Care prevention of
      Hypercholesterolemia].

PMID- 14651829
TI  - [Incidence and clinical characteristics of maculopapular exanthemas of viral
      aetiology].
AB  - OBJECTIVE: To estimate the incidence of maculo-papular viral exanthemas and to
      describe the epidemiological and clinical patterns. DESIGN: Observational
      descriptive study with a sample design. PARTICIPANTS AND SETTING: 154
      practitioners from the Castilla y Leon Sentinel Network with a surveilled
      population of 23 237 people-year under 15 years old, notified in 2002 the cases
      of diseases by means of a standard form with the variables and inclusion and
      exclusion criteria. MAIN MEASUREMENTS: It was included the maculo-papular
      exanthemas associated to a presumable systemic virus disease in patients under 15
      years old. It was excluded the infectious mononucleose, the chickenpox, and other
      non viral infections or exanthemas. RESULTS: 368 cases were notified which
      represent a incidence rate of 158.37 cases per 10 000 (95% CI, 142.31-174.42).
      The incidence was maximum under four years old, more than 350 per 10 000,
      decreasing significantly in children over this age. Erythema infectiousum
      presented the highest rate, followed by exanthema subitum. The exanthemas caused
      by measles or rubella were insignificants. CONCLUSIONS: Childhood exanthematous
      diseases of presumable viral etiology have an important incidence in primary
      care, although the majorities are banal and self-limited diseases. Clinical
      characteristics supported the suspicion diagnosis, which was consistent with the
      observed epidemiological description and expected presentations of each disease.
      Although serological analysis could diminish the uncertainly on notification and
      control of diseases submited to especial programs of vaccination and eradication,
      they would not improve substantially the diagnosis and treatment of these
      patients.

PMID- 14651830
TI  - [How do we refer to mental health from primary care?].
AB  - OBJECTIVES: To describe referrals from primary care (PC) to mental health (MH)
      and to study the diagnostic and therapeutic concordance between the two. DESIGN:
      Retrospective, descriptive study. SETTING: Gava II Primary Care Centre,
      Barcelona.Participants. All patients referred to MH in 1998, 1999 and 2000
      (n=380). MAIN MEASUREMENTS: The following from the referral form and PC medical
      records were analysed: general diagnosis, drugs treatment, number of words in the
      report, and purpose of referral; and on the first visit to MH: general diagnosis
      and drugs treatment. The kappa index was used to analyse the concordance between
      the diagnostic and therapeutic groups. RESULTS: There were 380 referrals, 63.4%
      of which were women. Information was obtained from the referral form in 81.6% of
      cases. In 50.7% the reason for referral was for the case to be supervised; and in
      12.4% the reason was not recorded. 18.7% (71 cases) did not attend their first MH
      appointment and waited an average of 78 days (SD=70.9) until the appointment. As
      92 cases were lost (71 who did not attend and 21 for whom insufficient
      information was obtained), only 288 cases were analysed.The greatest diagnostic
      concordance between PC and MH was in mental deficiency (kappa=0.85) and psychotic
      disorder (kappa=0.77); and the minimum was in anxiety-depressive disorder
      (kappa=0.24). The maximum degree of therapeutic concordance was for neuroleptic
      drugs (kappa=0.66). CONCLUSIONS: The diagnostic and therapeutic concordance
      between PC and MH is weak. The referral sheet is not present in a great many
      cases. The waiting-time until the first consultation may explain patient
      absenteeism.

PMID- 14651831
TI  - [SARS: a new illness unmasked].

PMID- 14651832
TI  - [Reckless perforations. Brief description of the piercing phenomenon and its
      possible complications].

PMID- 14651833
TI  - [Elder Abuse at home. Current situation and possible intervention strategies].

PMID- 14651834
TI  - [Cardiovascular morbidity in a general population 7 years after calculation of
      their cardiovascular risk].

PMID- 14651835
TI  - [Depressive disorder and cognitive deterioration in the elderly population
      attending for consultation].

PMID- 14651836
TI  - [Collagenous colitis. Presentation of four new cases].

PMID- 14651837
TI  - [Reversible bigeminy with levothyroxine].

PMID- 14651838
TI  - [Concerning a case of chronic urticaria due to intestinal parasites].

PMID- 14651839
TI  - [On the use of antibiotics in primary care].

PMID- 14651840
TI  - [Voluntary termination of pregnancy and illegal abortion. Reflections of a family
      doctor].

PMID- 14651841
TI  - The BRCA2-EMSY connection: implications for breast and ovarian tumorigenesis.
AB  - In this issue, Hughes-Davies et al. describe a novel gene product, EMSY, which
      suppresses the transactivational activity of BRCA2. EMSY is located within an
      amplicon in sporadic breast and ovarian cancers, suggesting that its
      overexpression may mimic the effects of BRCA2 inactivation. The implications for
      BRCA2 function are discussed.

PMID- 14651842
TI  - Rad53: a controller ensuring the fine-tuning of histone levels.
AB  - Checkpoint proteins are activated in response to genotoxic insults or replication
      stress to maintain genome integrity. Their function is believed to depend largely
      on the detection of the DNA damage or defects occurring during replication fork
      progression.

PMID- 14651843
TI  - Brain or brawn: how FGF signaling gives us both.
AB  - How does FGF (fibroblast growth factor) signaling induce both neural and
      mesodermal cell fates in the early embryo? Two papers address this fundamental
      question in this issue of Cell. Bertrand et al. show in the ascidian that a GATA
      factor determines the neural response of animal cells to FGF signaling, while in
      the chick, Sheng et al. demonstrate that the slow induction by FGF of a new
      transcription factor (Churchill) in the neural plate in turn induces expression
      of Sip1 (Smad interacting protein-1), which inhibits mesodermal genes and
      sensitizes cells to later neural inducing factors.

PMID- 14651844
TI  - Endocytosis and signaling: a relationship under development.
AB  - The ability to internalize macromolecules by endocytosis is a property of all
      eukaryotic cells. Frontline research on endocytosis has been presented in a
      successful series of biannual meetings in Europe. This year's meeting on
      "Membrane Dynamics in Endocytosis" was held September 13-18 in Acquafredda di
      Maratea, on the coast of southern Italy. Four key questions were addressed: What
      are the molecular mechanisms of endocytic membrane trafficking? How does
      endocytosis modulate receptor signaling and vice versa? What is the importance of
      endocytosis during development? How do endocytic organelles contribute to
      immunity or susceptibility to pathogens?

PMID- 14651845
TI  - EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer.
AB  - The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product
      is implicated in DNA repair and transcriptional regulation. Here we identify a
      protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY
      is capable of silencing the activation potential of BRCA2 exon 3, associates with
      chromatin regulators HP1beta and BS69, and localizes to sites of repair following
      DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in
      breast and ovarian cancer. We show that the EMSY gene is amplified almost
      exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer
      (17%). In addition, EMSY amplification is associated with worse survival,
      particularly in node-negative breast cancer, suggesting that it may be of
      prognostic value. The remarkable clinical overlap between sporadic EMSY
      amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic
      breast and ovarian cancer.

PMID- 14651846
TI  - A Rad53 kinase-dependent surveillance mechanism that regulates histone protein
      levels in S. cerevisiae.
AB  - Rad53 and Mec1 are protein kinases required for DNA replication and recovery from
      DNA damage in Saccharomyces cerevisiae. Here, we show that rad53, but not mec1
      mutants, are extremely sensitive to histone overexpression, as Rad53 is required
      for degradation of excess histones. Consequently, excess histones accumulate in
      rad53 mutants, resulting in slow growth, DNA damage sensitivity, and chromosome
      loss phenotypes that are significantly suppressed by a reduction in histone gene
      dosage. Rad53 monitors excess histones by associating with them in a dynamic
      complex that is modulated by its kinase activity. Our results argue that Rad53
      contributes to genome stability independently of Mec1 by preventing the damaging
      effects of excess histones both during normal cell cycle progression and in
      response to DNA damage.

PMID- 14651847
TI  - The hyperpolarization-activated HCN1 channel is important for motor learning and
      neuronal integration by cerebellar Purkinje cells.
AB  - In contrast to our increasingly detailed understanding of how synaptic plasticity
      provides a cellular substrate for learning and memory, it is less clear how a
      neuron's voltage-gated ion channels interact with plastic changes in synaptic
      strength to influence behavior. We find, using generalized and regional knockout
      mice, that deletion of the HCN1 channel causes profound motor learning and memory
      deficits in swimming and rotarod tasks. In cerebellar Purkinje cells, which are a
      key component of the cerebellar circuit for learning of correctly timed
      movements, HCN1 mediates an inward current that stabilizes the integrative
      properties of Purkinje cells and ensures that their input-output function is
      independent of the previous history of their activity. We suggest that this
      nonsynaptic integrative function of HCN1 is required for accurate decoding of
      input patterns and thereby enables synaptic plasticity to appropriately influence
      the performance of motor activity.

PMID- 14651848
TI  - Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF
      kappaB activation by genotoxic stress.
AB  - The transcription factor NF-kappaB is critical for setting the cellular
      sensitivities to apoptotic stimuli, including DNA damaging anticancer agents.
      Central to NF-kappaB signaling pathways is NEMO/IKKgamma, the regulatory subunit
      of the cytoplasmic IkappaB kinase (IKK) complex. While NF-kappaB activation by
      genotoxic stress provides an attractive paradigm for nuclear-to-cytoplasmic
      signaling pathways, the mechanism by which nuclear DNA damage modulates NEMO to
      activate cytoplasmic IKK remains unknown. Here, we show that genotoxic stress
      causes nuclear localization of IKK-unbound NEMO via site-specific SUMO-1
      attachment. Surprisingly, this sumoylation step is ATM-independent, but nuclear
      localization allows subsequent ATM-dependent ubiquitylation of NEMO to ultimately
      activate IKK in the cytoplasm. Thus, genotoxic stress induces two independent
      signaling pathways, SUMO-1 modification and ATM activation, which work in concert
      to sequentially cause nuclear targeting and ubiquitylation of free NEMO to permit
      the NF-kappaB survival pathway. These SUMO and ubiquitin modification pathways
      may serve as anticancer drug targets.

PMID- 14651849
TI  - TSC2 mediates cellular energy response to control cell growth and survival.
AB  - Mutations in either the TSC1 or TSC2 tumor suppressor gene are responsible for
      Tuberous Sclerosis Complex. The gene products of TSC1 and TSC2 form a functional
      complex and inhibit the phosphorylation of S6K and 4EBP1, two key regulators of
      translation. Here, we describe that TSC2 is regulated by cellular energy levels
      and plays an essential role in the cellular energy response pathway. Under energy
      starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates
      TSC2 and enhances its activity. Phosphorylation of TSC2 by AMPK is required for
      translation regulation and cell size control in response to energy deprivation.
      Furthermore, TSC2 and its phosphorylation by AMPK protect cells from energy
      deprivation-induced apoptosis. These observations demonstrate a model where TSC2
      functions as a key player in regulation of the common mTOR pathway of protein
      synthesis, cell growth, and viability in response to cellular energy levels.

PMID- 14651850
TI  - Local, efflux-dependent auxin gradients as a common module for plant organ
      formation.
AB  - Plants, compared to animals, exhibit an amazing adaptability and plasticity in
      their development. This is largely dependent on the ability of plants to form new
      organs, such as lateral roots, leaves, and flowers during postembryonic
      development. Organ primordia develop from founder cell populations into organs by
      coordinated cell division and differentiation. Here, we show that organ formation
      in Arabidopsis involves dynamic gradients of the signaling molecule auxin with
      maxima at the primordia tips. These gradients are mediated by cellular efflux
      requiring asymmetrically localized PIN proteins, which represent a functionally
      redundant network for auxin distribution in both aerial and underground organs.
      PIN1 polar localization undergoes a dynamic rearrangement, which correlates with
      establishment of auxin gradients and primordium development. Our results suggest
      that PIN-dependent, local auxin gradients represent a common module for formation
      of all plant organs, regardless of their mature morphology or developmental
      origin.

PMID- 14651851
TI  - Churchill, a zinc finger transcriptional activator, regulates the transition
      between gastrulation and neurulation.
AB  - Gastrulation generates mesoderm and endoderm from embryonic epiblast; soon after,
      the neural plate is established within the epiblast-both events require FGF
      signaling. We describe a zinc finger transcriptional activator, Churchill (ChCh),
      which acts as a switch between different roles of FGF. FGF induces ChCh slowly;
      this activates Smad-interacting-protein-1 (Sip1), which blocks further induction
      of the mesoderm markers brachyury and Tbx6L by FGF. ChCh is first expressed as
      cells stop migrating through the primitive streak, and we show that it regulates
      cell ingression. We propose a simple mechanism by which FGF sensitizes cells to
      BMP signals. These results reveal that neural induction requires cessation of
      mesoderm formation at the midline in addition to the decision between epidermis
      and neural plate.

PMID- 14651852
TI  - Neural tissue in ascidian embryos is induced by FGF9/16/20, acting via a
      combination of maternal GATA and Ets transcription factors.
AB  - In chordates, formation of neural tissue from ectodermal cells requires an
      induction. The molecular nature of the inducer remains controversial in
      vertebrates. Here, using the early neural marker Otx as an entry point, we
      dissected the neural induction pathway in the simple embryos of Ciona
      intestinalis. We first isolated the regulatory element driving Otx expression in
      the prospective neural tissue, showed that this element directly responds to FGF
      signaling and that FGF9/16/20 acts as an endogenous neural inducer. Binding site
      analysis and gene loss of function established that FGF9/16/20 induces neural
      tissue in the ectoderm via a synergy between two maternal response factors.
      Ets1/2 mediates general FGF responsiveness, while the restricted activity of
      GATAa targets the neural program to the ectoderm. Thus, our study identifies an
      endogenous FGF neural inducer and its early downstream gene cascade. It also
      reveals a role for GATA factors in FGF signaling.

PMID- 14651853
TI  - Integrated analysis of protein composition, tissue diversity, and gene regulation
      in mouse mitochondria.
AB  - Mitochondria are tailored to meet the metabolic and signaling needs of each cell.
      To explore its molecular composition, we performed a proteomic survey of
      mitochondria from mouse brain, heart, kidney, and liver and combined the results
      with existing gene annotations to produce a list of 591 mitochondrial proteins,
      including 163 proteins not previously associated with this organelle. The protein
      expression data were largely concordant with large-scale surveys of RNA abundance
      and both measures indicate tissue-specific differences in organelle composition.
      RNA expression profiles across tissues revealed networks of mitochondrial genes
      that share functional and regulatory mechanisms. We also determined a larger
      "neighborhood" of genes whose expression is closely correlated to the
      mitochondrial genes. The combined analysis identifies specific genes of
      biological interest, such as candidates for mtDNA repair enzymes, offers new
      insights into the biogenesis and ancestry of mammalian mitochondria, and provides
      a framework for understanding the organelle's contribution to human disease.

PMID- 14651855
TI  - Whole genome shotgun sequencing guided by bioinformatics pipelines--an optimized
      approach for an established technique.
AB  - While the sequencing of bacterial genomes has become a routine procedure at major
      sequencing centers, there are still a number of genome projects at small- or
      medium-size facilities. For these facilities a maximum of control over
      sequencing, assembling and finishing is essential. At the same time, facilities
      have to be able to co-operate at minimum costs for the overall project. We have
      established a pipeline for the distributed sequencing of Alcanivorax borkumensis
      SK2, Azoarcus sp. BH72, Clavibacter michiganensis subsp. michiganensis NCPPB382,
      Sorangium cellulosum So ce56 and Xanthomonas campestris pv. vesicatoria 85-10.
      Our pipeline relies on standard tools (e.g. PHRED/PHRAP, CAP3 and
      Consed/Autofinish) wherever possible, supplementing them with new tools (BioMake
      and BACCardI) to achieve the aims described above.

PMID- 14651856
TI  - EMMA: a platform for consistent storage and efficient analysis of microarray
      data.
AB  - As a high throughput technique, microarray experiments produce large data sets,
      consisting of measured data, laboratory protocols, and experimental settings. We
      have implemented the open source platform EMMA to store and analyze these data.
      The system provides automated pipelines for data processing and has a modular
      architecture that can be easily extended. EMMA features detailed reports about
      spots and their corresponding measurements. In addition to routine data analysis
      algorithms, the system can be integrated with other components that contain
      additional data sources (e.g. genome annotation systems).

PMID- 14651857
TI  - Bioinformatics support for high-throughput proteomics.
AB  - In the "post-genome" era, mass spectrometry (MS) has become an important method
      for the analysis of proteome data. The rapid advancement of this technique in
      combination with other methods used in proteomics results in an increasing number
      of high-throughput projects. This leads to an increasing amount of data that
      needs to be archived and analyzed. To cope with the need for automated data
      conversion, storage, and analysis in the field of proteomics, the open source
      system ProDB was developed. The system handles data conversion from different
      mass spectrometer software, automates data analysis, and allows the annotation of
      MS spectra (e.g. assign gene names, store data on protein modifications). The
      system is based on an extensible relational database to store the mass spectra
      together with the experimental setup. It also provides a graphical user interface
      (GUI) for managing the experimental steps which led to the MS data. Furthermore,
      it allows the integration of genome and proteome data. Data from an ongoing
      experiment was used to compare manual and automated analysis. First tests showed
      that the automation resulted in a significant saving of time. Furthermore, the
      quality and interpretability of the results was improved in all cases.

PMID- 14651858
TI  - Building a BRIDGE for the integration of heterogeneous data from functional
      genomics into a platform for systems biology.
AB  - The flood of data acquired from the increasing number of publicly available
      genomes has led to new demands for bioinformatics software. With the growing
      amount of information resulting from high throughput experiments new questions
      arise that often focus on the comparison of genes, genomes, and their expression
      profiles. Inferring new knowledge by combining different kinds of "post-genomics"
      data obviously necessitates the development of new approaches that allow the
      integration of variable data sources into a flexible framework. In this paper, we
      describe our concept for the integration of heterogeneous data into a platform
      for systems biology. We have implemented a Bioinformatics Resource for the
      Integration of heterogeneous Data from Genomic Explorations (BRIDGE) and
      illustrate the usability of our approach as a platform for systems biology for
      two sample applications.

PMID- 14651859
TI  - Azoarcus sp. strain BH72 as a model for nitrogen-fixing grass endophytes.
AB  - The availability of nitrogen often limits plant growth in terrestrial ecosystems.
      The only biological reaction counterbalancing the loss of N from soils or
      ecosystems is biological nitrogen fixation, the enzymatic reduction of N2 to
      ammonia. Some gramineous crops such as certain Brazilian sugar cane cultivars or
      Kallar grass can derive a substantial part of the plant nitrogen from biological
      nitrogen fixation. Our research on grass-associated diazotrophs focuses on
      endophytic bacteria, microorganisms that multiply and spread inside plants
      without causing damage of the host plants or conferring an ecological threat to
      the plant. This review summarizes the current knowledge on the diazotrophic
      endophyte Azoarcus sp. BH72, which is capable of colonizing the interior of rice
      roots, one of the globally most important crops.

PMID- 14651860
TI  - Clavibacter michiganensis subsp. michiganensis: first steps in the understanding
      of virulence of a Gram-positive phytopathogenic bacterium.
AB  - Clavibacter michiganensis subsp. michiganensis is a plant-pathogenic
      actinomycete. It infects tomato, spreads through the xylem and causes bacterial
      wilt and canker. The wild-type strain NCPPB382 carries two plasmids, pCM1 and
      pCM2. The cured plasmid-free derivative CMM100 is still able to colonize tomato,
      but no disease symptoms develop indicating that all genes required for successful
      infection, establishment and growth in the plant reside on the chromosome. Both
      plasmids carry one virulence factor, a gene encoding a cellulase, CelA in case of
      pCM1 and a putative serine protease Pat-1 on pCM2. These genes can independently
      convert the non-virulent strain CMM100 into a pathogen causing wilt on tomatoes.
      Currently, genome projects for Cmm and the closely related potato-pathogen C.
      michiganensis subsp. sepedonicus have been initiated. The data from the genome
      project shall give clues on further genes involved in plant-microbe interaction
      that can be tested experimentally. Especially, identification of genes related to
      host-specificity through genome comparison of the two subspecies might be
      possible.

PMID- 14651861
TI  - Comparison of two Xanthomonas campestris pathovar campestris genomes revealed
      differences in their gene composition.
AB  - For the Xanthomonas campestris pathovar campestris wild-type strain B100 a
      plasmid-based clone library was constructed. The plasmids carried chromosomal
      fragments of 3-4 kb in size that were tagged in vitro with the artificial
      transposon KAN-2. More than 3000 of the transposon target sites were
      characterized by DNA sequencing. The sequences obtained were compared to the
      recently published genome of Xanthomonas campestris pathovar campestris strain
      ATCC 33913. Most of the sequenced clones derived from strain B100 matched the
      chromosomal sequence of strain ATCC 33913. An alignment to the circular map of
      this chromosome revealed that the similarities were statistically distributed
      over the entire genome of strain ATCC 33913. The similarity was obvious for
      protein coding sequences, as well as for mobile genetic elements. However, four
      regions in the genome of Xanthomonas campestris pathovar campestris strain ATCC
      33913, ranging in size from 11 to 37 kb, were not represented in the sequenced
      clone library of Xanthomonas campestris pathovar campestris strain B100. On the
      other hand, 1.2% of the sequenced clones originating from Xanthomonas campestris
      pathovar campestris strain B100 showed no or insignificant similarities to the
      genome of strain ATCC 33913.

PMID- 14651862
TI  - Genomic approaches in Xanthomonas campestris pv. vesicatoria allow fishing for
      virulence genes.
AB  - Xanthomonas campestris pv. vesicatoria is an economically important pathogen of
      pepper and tomato and has been established as a model organism to study bacterial
      infection strategies. In the last two decades, intensive genetic and molecular
      analyses led to the isolation of many genes that play a role in the intimate
      molecular relationship with the host plant. Essential for pathogenicity is a type
      III protein secretion system, which delivers bacterial effector proteins into the
      host cell. Currently, the genome of X. campestris pv. vesicatoria is being
      sequenced. The availability of genomic sequence information will pave the way for
      the identification of new bacterial virulence factors by bioinformatic
      approaches. In this article, we will present preliminary data from the genomic
      sequence analysis and describe recent and novel studies to identify bacterial
      type III effector genes.

PMID- 14651863
TI  - Genome sequence completed of Alcanivorax borkumensis, a hydrocarbon-degrading
      bacterium that plays a global role in oil removal from marine systems.
AB  - In this paper, we provide background to the genome sequencing project of
      Alcanivorax borkumensis, which is a marine bacterium that uses exclusively
      petroleum oil hydrocarbons as sources of carbon and energy (therefore designated
      "hydrocarbonoclastic"). It is found in low numbers in all oceans of the world and
      in high numbers in oil-contaminated waters. Its ubiquity and unusual physiology
      suggest it is globally important in the removal of hydrocarbons from polluted
      marine systems. A functional genomics analysis of Alcanivorax borkumensis strain
      SK2 was recently initiated, and its genome sequence has just been completed.
      Annotation of the genome, metabolome modelling, and functional genomics, will
      soon reveal important insights into the genomic basis of the properties and
      physiology of this fascinating and globally important bacterium.

PMID- 14651864
TI  - Exploiting the genetic potential of polyketide producing streptomycetes.
AB  - Streptomycetes are the most important bacterial producers of bioactive secondary
      metabolites such as antibiotics or cytostatics. Due to the emerging resistance of
      pathogenic bacteria to all commonly used antibiotics, new and modified natural
      compounds are required for the development of novel drugs. In addition to the
      classical screening for natural compounds, genome driven approaches like
      combinatorial biosynthesis are permanently gaining relevance for the generation
      of new structures. This technology utilizes the combination of genes from
      different biosynthesis pathways resulting in the production of novel or modified
      metabolites. The basis for this strategy is the access to a significant number of
      genes and the knowledge about the activity and specificity of the enzymes encoded
      by them. A joint initiative was started to exploit the biosynthesis gene clusters
      from streptomycetes. In this publication, an overview of the strategy for the
      identification and characterization of numerous biosynthesis gene clusters for
      polyketides displaying interesting functions and particular structural features
      is given.

PMID- 14651865
TI  - Myxobacteria: proficient producers of novel natural products with various
      biological activities--past and future biotechnological aspects with the focus on
      the genus Sorangium.
AB  - Myxobacteria are gram-negative bacteria which are most noted for their ability to
      form fruiting bodies upon starvation. Within the last two decades, they
      increasingly gained attention as producers of natural products with biological
      activity. Here, recent and future biotechnological research on certain key
      myxobacteria and on their ability to produce natural products is reviewed with
      the focus on the production of myxovirescin, soraphen and epothilone. Aspects of
      product improvement and yield as well as statistics regarding secondary
      metabolite formation are discussed. Future research will deal with the
      exploitation of the biosynthetic potential of the myxobacteria, for example via
      the isolation of new myxobacterial species with different physiological
      properties. Additionally, the genetic potential of myxobacteria to form natural
      products can be exploited by the identification and activation of biosynthetic
      gene clusters. These can be found frequently within their genomes, which is shown
      by the analysis of the unfinished genomes of Myxococcus xanthus and Sorangium
      cellulosum. The current status of the S. cellulosum functional genome project
      with model strain So ce56 is discussed.

PMID- 14651867
TI  - Development of a Corynebacterium glutamicum DNA microarray and validation by
      genome-wide expression profiling during growth with propionate as carbon source.
AB  - A DNA microarray was developed to analyse global gene expression of the amino
      acid-producing bacterium Corynebacterium glutamicum. PCR products representing
      93.4% of the predicted C. glutamicum genes were prepared and spotted in
      quadruplicate onto 3-aminopropyltrimethoxysilane-coated glass slides. The
      applicability of the C. glutamicum DNA microarray was demonstrated by co
      hybridisation with fluorescently labelled cDNA probes. Analysis of the technical
      variance revealed that C. glutamicum genes detected with different intensities
      resulting in ratios greater than 1.52 or smaller than -1.52 can be regarded as
      differentially expressed with a confidence level of greater than 95%. In a
      validation example, we measured changes of the mRNA levels during growth of C.
      glutamicum with acetate and propionate as carbon sources. Acetate-grown C.
      glutamicum cultures were used as reference. At the 95% confidence interval, 117
      genes revealed increased transcript levels in the presence of propionate, while
      43 genes showed a decreased expression compared with the acetate-grown culture.
      Global expression profiling confirmed the induction of the prpD2B2C2 gene cluster
      already known to be essential for propionate degradation via the 2-methylcitrate
      cycle. Besides many genes of unknown function, the paralogous prpD1B1C1 gene
      cluster as well as fasI-B (encoding fatty-acid synthase IB), dtsR1 and dtsR2
      (components of acyl-CoA carboxylases), gluABCD (glutamate transport system), putP
      (proline transport system), and pyc (pyruvate carboxylase) showed significantly
      increased expression levels. Differential expression of these genes was confirmed
      by real-time reverse transcription (RT) PCR assays.

PMID- 14651866
TI  - Construction and validation of a Sinorhizobium meliloti whole genome DNA
      microarray: genome-wide profiling of osmoadaptive gene expression.
AB  - Based on the complete Sinorhizobium meliloti genome sequence we established DNA
      microarrays as a comprehensive tool for systematic genome-wide gene expression
      analysis in S. meliloti 1021. For these PCR fragment-based microarrays, called
      Sm6kPCR, a collection of probes for the 6207 predicted protein-coding genes
      consisting of 6046 gene-specific PCR fragments and 161 70 mer oligonucleotides
      was arrayed in high density on glass slides. To obtain these PCR fragments primer
      pairs were designed to amplify internal gene-specific DNA fragments of 80-350 bp.
      Additionally, these primers were characterized by a 5' extension that allowed for
      reamplification using standard primers after the first amplification employing
      the specific primers. In order to ascertain the quality of the Sm6kPCR
      microarrays and to validate gene expression studies in S. meliloti parallel
      hybridizations based on RNA samples obtained from cells cultured under identical
      conditions were performed. In addition, gene expression in S. meliloti in
      response to an osmotic upshift imposed by the addition of 0.38 M NaCl was
      monitored. 137 genes were identified showing significant changes in gene
      expression resulting from the osmotic upshift. From these genes 52 were induced
      and 85 genes were repressed. Among the genes displaying different RNA levels some
      functional groups could be identified that are particularly remarkable.
      Repression was observed for 8 genes related to motility and chemotaxis, 7 genes
      encoding amino acid biosynthesis enzymes and 15 genes involved in iron uptake
      whereas 14 genes involved in transport of small molecules and 4 genes related to
      polysaccharide biosynthesis were induced.

PMID- 14651868
TI  - Qualitative and quantitative proteomics by two-dimensional gel electrophoresis,
      peptide mass fingerprint and a chemically-coded affinity tag (CCAT).
AB  - The chemically-coded affinity tag (CCAT) method combines standard electrophoresis
      protocols with MALDI-TOF-MS analysis to identify and quantify protein abundances
      in complex samples in one step. This method is designed to fit into the workflow
      of SDS-PAGE or two-dimensional electrophoresis (2-DE) only requiring basic
      proteome laboratory equipment. Prior to electrophoresis two protein samples are
      separately labelled with a heavy or a light version of the CCAT reagent via
      reduced cysteines in the proteins. Equal amounts are then combined and
      electrophoretically separated. Proteins can then be excised from the gel to
      obtain their peptide mass fingerprint by mass spectrometry. This fingerprint
      enabled not only identification, but also quantification by comparing relative
      peak intensities of CCAT-labelled peptides. In this article, we display how the
      CCAT method can be used to analyse two protein samples in one gel and that the
      peak intensities of labelled peptides reflect the abundance of a protein in it.

PMID- 14651869
TI  - Investigation of Neospora sp. antibodies in aborted mares from Normandy, France.
AB  - Neospora caninum, an apicomplexan protozoan parasite, is recognized as a major
      cause of abortion in cattle while limited information is presently available on
      association between equine Neospora infections and abortions. The aim of the
      present study was to document prevalence of antibodies against Neospora sp. in
      aborted mares as a clue to the role of N. caninum in mare reproductive failure in
      Normandy, France. Using an agglutination test, the number of animals with
      elevated (>80) anti-Neospora sp. antibody titer was higher in a group of 54
      aborted mares than in randomly chosen groups of 45 mares and 76 horses sampled
      for equine arteritis virus and Fasciola hepatica antibodies, respectively
      (P<0.001). N. caninum DNA was found in 3/91 fetal brains, 2/77 fetal hearts, and
      1/1 placenta, and present in both brains and hearts of two fetuses. In 13 cases
      for which both mare serum and fetus were available, no fetal N. caninum
      amplification product was present while a large variation of maternal antibody
      titers was found. Data prompt at additional surveys of association between equine
      reproductive failure and Neospora sp. infection.

PMID- 14651870
TI  - Seroprevalence and associated risk factors of neosporosis in beef and dairy
      cattle in Italy.
AB  - A cross-sectional serological survey for Neospora caninum was carried out on beef
      and dairy cattle in southern and northern Italy. A total of 111 herds and 1140
      animals were tested using an ELISA assay (CHEKIT-Neospora) to detect anti-N.
      caninum antibodies. Management and individual data were collected and analysed
      both by linear and logistic multiple-regression models in order to find good
      predictors of the cattle seroprevalence and anti-N. caninum antibody level. At
      least one seropositive animal was found in 49 herds (44.1%), of which 31 (39.7%)
      from southern Italy and 18 (54.5%) from northern Italy. A total of 126 head of
      cattle (11%) were found to be seropositive and the seroprevalence was lower in
      southern (8.7%) than in northern Italy (16%). One of the best predictors of
      neosporosis seroprevalence in this study was the practice of self-rearing
      replacement heifers. Further risk factors were linked to higher stocking density,
      i.e. animals farmed in large herds and with no summer or permanent grazing
      practices were more likely to be seropositive than others. Farms with two or more
      dogs had higher herd seropositivity than farms with one or no dogs and this
      factor interacted significantly with the farm size and presence of poultry. Among
      individual characteristics, seropositivity was higher in animals sampled in mid-
      or late-pregnancy compared to animals either in early pregnancy or not pregnant.
      There was a significant interaction between the factors for pregnancy status and
      grazing practices. None of the epidemiological data recorded was a good predictor
      of the anti-N. caninum antibody level.

PMID- 14651871
TI  - A metallo phosphatase activity present on the surface of Trypanosoma brucei
      procyclic forms.
AB  - In this work, we describe how living cells of Trypanosoma brucei procyclic forms
      were able to hydrolyze extracellular p-nitrophenylphosphate (pNPP). These intact
      parasites, which had their viability determined by motility and the Trypan blue
      method, presented a low level of pNPP hydrolysis in the absence of any divalent
      metal (0.72+/-0.07 nmol pNP/mg min). Interestingly, in the presence of 5mM
      MgCl(2), ectophosphatase activity of 1.91+/-0.21 nmol pNP/mg min was observed.
      The ectophosphatase activity was also stimulated by MnCl(2), CoCl(2) and CuCl(2)
      but not by CaCl(2) and CdCl(2) and was inhibited by ZnCl(2). The addition of
      Mg(2+), Mn(2+), Co(2+) and Cu(2+) to extracellular medium increased the
      ectophosphatase activity in a dose-dependent manner. At 5mM pNPP, half-maximal
      stimulation of pNPP hydrolysis was obtained with 0.39+/-0.05 mM MgCl(2), 0.33+/
      0.03 mM MnCl(2), 1.63+/-0.12 mM CoCl(2) and 2.04+/-0.33 mM CuCl(2). In the
      absence of any divalent metal (basal activity) the apparent K(m) for pNPP was
      0.66+/-0.09 mM, while at saturating MgCl(2) concentrations the corresponding
      apparent K(m) for pNPP for Mg(2+)-stimulated phosphatase activity (difference
      between total minus basal phosphatase activity) was 0.27+/-0.03 mM. The Mg(2+)
      stimulated pNPP hydrolysis was strongly inhibited by ZnCl(2) and vanadate, while
      the metal-independent basal phosphatase activity was less inhibited by these
      phosphotyrosyl phosphatase inhibitors.

PMID- 14651873
TI  - Scanning electron microscopy study of Trichomonas gallinae.
AB  - A scanning electron microscopy (SEM) study of Trichomonas gallinae (Rivolta,
      1878), provided more information about the morphology of this flagellated
      protozoan. SEM showed the morphological features of the trophozoites; the
      emergence of the anterior flagella, the structure of the undulating membrane, the
      position and shape of the pelta, axostyle and posterior flagellum. Of special
      interest were the pseudocyst forms.

PMID- 14651872
TI  - Analysis of cross-reactivity of five new chicken monoclonal antibodies which
      recognize the apical complex of Eimeria using confocal laser immunofluorescence
      assay.
AB  - For Apicomplexa (members) the host cell invasion is realized with the help of the
      organelles located at the apical tip of parasites. In this research paper the
      characterization of five chicken monoclonal antibodies (mabs) produced against
      Eimeria acervulina sporozoites is described. All mabs reacted with molecules
      belonging to the apical complex of chicken Eimeria sporozoites. On
      immunofluorescence assay (IFA) one mab, 8E-1, recognized an apical tip molecule
      present on all chicken Eimeria sporozoites, two mabs (8D-2 and HE-4) recognized
      an antigen present on the apical tip of the same two Eimeria species (E.
      acervulina and E. brunetti), another mab (5D-11) recognized an antigen present on
      the apical tip of other two species (E. acervulina and E. maxima) while one mab
      (8C-3) identified antigens present on the sporozoites and sporocysts wall of only
      E. acervulina. Besides the apical tip antigens, two mabs (HE-4 and 8D-2)
      recognized some proteins located in the anterior half of the sporozoites.
      Collectively, these mabs proved that the apical complex of chicken Eimeria
      sporozoites share one or more antigens that are expected to play a role in host
      cell recognition and invasion.

PMID- 14651874
TI  - Antibodies to Neospora caninum in wild animals from Kenya, East Africa.
AB  - The prevalence of antibodies to Neospora caninum was examined in six wild
      Artiodactyla species, and in five wild Carnivora species from Kenya. Blood sera
      (104 wild ungulates from Marula Estates (MEs), and 31 wild carnivores from Masai
      Mara reserve and from other wildlife areas in northern and Southern Kenya), were
      screened using a Neospora agglutination test (NAT), with a twofold dilution (1:40
      1:320 titres). Presence of NAT antibodies to N. caninun is reported here for the
      first time in zebra (Equus burchelli), eland (Taurotragus oryx), African buffalo
      (Syncerus caffer), Thompson gazelle (Gazella thompsoni), impala (Aepyceros
      melampus), warthog (Phacochoerus aethiopicus), spotted hyena (Crocuta crocuta)
      and in free-ranging cheetah (Acinonyx jubatus). At 1:80 dilution, prevalence was
      61.5% in eland, 58.5% in zebra, 19.2% in Thompson gazelle, 33.3% in warthog, 50%
      in African buffalo, 30% in lion (Panthera leo), 20% in cheetah, and 33.3% in
      spotted hyena. Antibodies up to 1:320 titre were detected in eland (38.4%), zebra
      (19.5%), Thompson gazelle (3.8%) and lion (5%). Amongst herbivores, sero
      prevalence was significantly (P<0.05) higher, at all dilutions, in
      "grazer/digger" species (e.g. eland and zebra) than in non-"grazer/digger"
      species (e.g. impala and Thompson gazelle). No antibodies to N. caninum were
      found in two leopards (Panthera pardus) and one serval (Felis serval). Our
      results indicates a steady presence of N. caninum in wild mammals from Kenya. The
      hypothesis of a sylvatic cycle of N. caninum could be suggested, but more data
      are needed to verify the hypothesis, as to evaluate the role of N. caninum
      infection on the dynamics of wild animals population in the study area.

PMID- 14651876
TI  - The effect of Duddingtonia flagrans on trichostrongyle infections of Saanen goats
      on pasture.
AB  - Four groups of nine Saanen goat does with a naturally acquired mixed
      trichostrongylid infection were grazed on four paddocks. Two groups received a
      daily dose of Duddingtonia flagrans at the rate of 5 x 10(7) chlamydospores per
      animal per day for the 26-day grazing period. After a 19-day pasture resting
      period, 20 worm free 12-week-old tracer kids were introduced to the paddocks for
      14 days prior to removal for worm burden analysis. Four groups of five does and
      four kids were drenched then turned out onto the paddocks and faecal egg count
      (FEC) monitored. The FEC between groups was comparable throughout the initial
      grazing period. There were significant reductions in number of Teladorsagia
      circumcincta (54.8%, P=0.004) and Haemonchus contortus (85.0%, P=0.02) worms
      recovered from tracer animals. FEC of animals subsequently grazing pasture were
      significantly reduced (P=0.036) with reductions of 44% observed 4 weeks post
      turnout. No significant difference was observed after 6 weeks grazing. This trial
      has demonstrated the potential of D. flagrans to reduce larval numbers on pasture
      grazed by goats under New Zealand conditions.

PMID- 14651875
TI  - Taeniosis-cysticercosis in man and animals in the Sierra of Northern Ecuador.
AB  - Taenia solium is endemic in the Andean region of Ecuador. The recent rediscovery
      of Taenia saginata in humans urges to reconsider some assumptions in relation to
      the epidemiology of the taeniosis/cysticercosis complex in this
      country.Therefore, data were compiled on the infection of both tapeworms in man
      and animals in Pichincha and Imbabura provinces in the Andean region, north of
      Quito. On post mortem inspection 3 out of 806 (0.37%) carcasses had T. saginata
      metacestodes, however, 35 sera out of 869 (4.03%) showed circulating antigen in a
      monoclonal antibody-based sandwich ELISA (Ag-ELISA). Porcine cysticercosis was
      detected in 15 out of 2896 (0.52%) carcasses and 93 out of 1032 serum samples
      (9.01%) were positive in Ag-ELISA. In humans, 4.99% (215 out of 4306) cases of
      antigen positives were found, whereas coprological examination of 1935 stools
      resulted in 30 positive cases (1.55%). The limited number of adult tapeworms (29)
      that were collected does not allow firm conclusions on the proportion of each
      species, but in total 21 specimen were identified as T. saginata and 8 as T.
      solium. These data have been discussed in view of the epidemiology of human
      cysticercosis.

PMID- 14651877
TI  - Internal parasites of free-ranging guanacos from Patagonia.
AB  - In the winter of 2000, a greater than 80% reduction in the guanaco population
      located in Cabo Dos Bahi;as Wildlife Reserve, Chubut, Argentina, was evident due
      to massive mortality attributed to starvation. Twelve guanacos were necropsied
      and samples were analyzed at the Parasitology Laboratory of Facultad de Ciencias
      Veterinarias, Universidad Nacional del Litoral. Fecal analysis revealed
      developmental stages of Nematodirus sp., Marshallagia sp., Trichuris sp. and
      Eimeria spp. Histopathological analysis showed the presence of Sarcocystis sp. in
      muscle and fascia cysts. Other parasites recovered included Dictyocaulus filaria,
      Trichuris tenuis and Moniezia expansa. Of these, D. filaria and M. expansa
      possibly reflect interactions with domestic sheep. This is the first time that T.
      tenuis has been reported in guanacos.

PMID- 14651878
TI  - Seasonal changes of gastrointestinal nematode burden in sheep under an intensive
      grazing system.
AB  - A study was conducted of the monthly fluctuations of worm burdens and arrested
      development of gastrointestinal (GI) nematodes in sheep from a commercial farm of
      the Ebro valley (Spain). Twenty-four previously helminth-free female lambs
      (permanent lambs) grazed together with a flock of 500 resident ewes for 12 months
      following a three lambing/2-year reproductive management system. Two helminth
      free lambs (tracer lambs) were added to the flock each month and allowed to graze
      for 4 weeks. Measurements were made of the population of infective larvae on the
      pasture, and of levels of serum pepsinogen and faecal worm eggs in ewes and
      lambs. Additionally, post-mortem worm counts from two tracer and two permanent
      lambs were used to establish the level of infection at monthly intervals. Three
      generations of parasites were identified in the experiment. The generation
      derived from eggs deposited the previous autumn gave rise to the first infection
      of the animals in January and May. This infection had low consequences for the
      animals, but it signified the initiation of infection and the resumption of the
      annual cycle of pasture contamination. The second generation, appearing between
      June and July, was the year's most important source of infection and gave rise to
      an outbreak of parasitism in permanent lambs. This was indicated by an increase
      in levels of serum pepsinogen, the appearance of diarrhoea, and an important
      decrease in lamb growth rates. The third wave of infection, occurring in October
      and November, there was less impact than the previous one with respect to the
      level of infection, but it was the origin of the future over-wintering
      population. Teladorsagia circumcincta was the predominant species, followed by
      Haemonchus contortus and Trichostrongylus colubriformis. The highest numbers of
      worm recovered from both the tracer and permanent lambs were observed in July,
      with average numbers of 7900 and 19,200, respectively. The inhibition phenomenon
      was more evident in permanent than in tracer lambs, and mainly affected H.
      contortus as evidenced by populations exhibiting arrested larvae values of over
      70% in January and February. Results obtained in this study confirm the
      epidemiological importance of the over-wintering L(3) generation as the initial
      source of the animal's infection and the origin of the annual resumption of
      pasture contamination cycles.

PMID- 14651879
TI  - The effect of dietary forage on the development and survival of helminth
      parasites in ovine faeces.
AB  - Studies in New Zealand and the UK have shown that lambs grazing birdsfoot trefoil
      (Lotus corniculatus) or chicory (Cichorium intybus) have reduced parasite
      intensities compared to lambs grazing ryegrass swards. However, data in the
      literature on the influence of forages on helminth parasites is equivocal and the
      underlying mechanisms by which different forage diets may affect these parasites
      have not been fully determined. The aim of the experiments reported here was to
      investigate the hypothesis that the consumption of these forages does not affect
      the hatching and development of helminth eggs in the faeces subsequently produced
      by the host animal. Lambs grazed monoculture swards of birdsfoot trefoil,
      chicory, Italian ryegrass (Lolium multiflorum)/red clover (Trifolium pratense) or
      perennial ryegrass (Lolium perenne)/white clover (Trifolium repens) for 5 weeks
      and faecal samples collected on days 14, 21, 28 and 35 directly from the rectum
      of each lamb were used to prepare replicate cultures for each forage type on each
      occasion. The experiment was repeated over two consecutive years but ryegrass/red
      clover was not included in Year 2. The dry matter of all faeces was made constant
      and the faeces were cultured at 27 degrees C for 7 days, before larvae were
      extracted, counted and identified according to genus or, where possible, species.
      Overall, the results showed that forage diet had no effect on egg hatchability
      but significantly affected the development/survival of infective helminth larvae
      in the faeces of the host animal. Furthermore, feeding birdsfoot trefoil to lambs
      was found to increase the percentage of helminth parasites that reached the
      infective stage in the subsequent faeces compared to other forages. Further work
      is needed to assess whether this would increase the number of larvae on birdsfoot
      trefoil swards overall under field conditions and to understand the implications
      of these findings in an applied farming system.

PMID- 14651880
TI  - Development, characterization, and lethal effect of monoclonal antibodies against
      hemocytes in an adult female tick, Ornithodoros moubata (Acari: Argasidae).
AB  - In the present study, 19 monoclonal antibodies (mAbs) against adult Ornithodoros
      moubata hemocytes were established, and the reactivity of the hemocytes to these
      mAbs was examined by an indirect fluorescent antibody test (IFAT), Western blot
      and immunoprecipitation analyses. It was shown that the reactivities of the
      hemocytes to the mAbs varied among morphologically similar hemocyte types, and
      most mAbs produced in the present study showed the multiple band reactivity.
      However, the presence of shared epitopes among peptide subunits of the same
      protein or entirely different proteins are not common, so their reactivity could
      not be explained in detail. These results suggest that there are morphologically
      similar but functionally differentiated hemocytes. Therefore, in addition to
      morphological classification, the molecular-based classification of the hemocytes
      is also required. In order to assess the lethal effect of blood meal containing
      each mAb, artificial feeding was performed. The OmHC 31 showed the strongest
      lethal effect on adult female O. moubata. In conclusion, anti-hemocyte mAbs
      produced in this study are useful not only for the immunological classification
      of hemocytes but also for the immunological control of the tick.

PMID- 14651881
TI  - Assessment of a low virulence Australian isolate of Anaplasma marginale for
      pathogenicity, immunogenicity and transmissibility by Boophilus microplus.
AB  - A 14-year-old cow (Dawn) born and kept in a Boophilus microplus-free region gave
      birth to a calf, which showed the presence of an Anaplasma marginale infection
      after splenectomy. The calf's grand dam was from a B. microplus infected area and
      we assume the infection originated via the transplacental route over two
      generations. An isolate, prepared from the calf, had similar or lower
      pathogenicity as Anaplasma centrale, and previously exposed steers were resistant
      to challenge by four A. marginale field isolates. Two attempts to transmit the
      isolate using B. microplus were unsuccessful. Our results indicate that Dawn A.
      marginale may be a useful vaccine in Australia and warrants larger scale
      validation of its safety and potency locally as well as of the protection it
      affords against African and New World isolates.

PMID- 14651882
TI  - Prevalence of zoonotic important parasites in the red fox (Vulpes vulpes) in
      Great Britain.
AB  - A national necropsy survey of red foxes was carried out across Great Britain to
      record Echinococcus, Trichinella and Toxoplasma. The survey did not record
      directly, or indirectly using coproantigen/PCR tests, evidence for the presence
      of Echinococcus multilocularis in 588 animals, although E. granulosus was
      suspected in six animals. Parasitological evidence for Trichinella spp. could not
      be found in 587 fox muscle digests, and a specific PCR test also failed to detect
      Toxoplasma in a sub-set of 61 random fox tongue biopsies. The upper 95%
      confidence interval for the above parasites was 0.60% (E. multilocularis), 0.60%
      (Trichinella spp.) and 5.6% (Toxoplasma). The commonest gut parasites were the
      hookworm Uncinaria stenocephala (41.3%) and the ascarid Toxocara canis (61.6%).
      This study also reports the second occurrence of Trichuris vulpis in Great
      Britain.

PMID- 14651883
TI  - Activity of the Pinus elliottii resin compounds against Lernaea cyprinacea in
      vitro.
AB  - Lernaea cyprinacea infestation is a major problem for fishing culture in Brazil,
      which was introduced in the mid-eighties. To attempt controlling this parasite,
      an evaluation of the activity of the Pinus elliottii resin constituents against
      it was undertaken. To run the bioassay, fish infested with L. cyprinaceae were
      transferred to aquaria and kept at room temperature and ventilation for 15 days
      for adaptation. Afterwards, fish were sacrificed and the parasites were kept
      under water to run the experiments by evaluating the activities of the steamed
      oil and the chloroform fraction of the resin at concentrations of 0.5, 1.0, 2.0
      and 5.0 ppm. The crude resin was also evaluated at concentrations of 1.0, 5.0 and
      10 ppm, as well as the major components of its steamed oil, alpha and beta
      pinenes, both at concentrations of 0.5 and 1.0 ppm. The results showed that both
      fractions from the resin were effective at 0.5 ppm concentration, while the pure
      compounds were less active. Moreover, the acute toxicity (DL(50)) of the crude
      resin for the fish Leptorinus piau, aged 1 month, was established at 200.0 ppm,
      which ensures its safe use.

PMID- 14651884
TI  - Canine onchocercosis in Greece: report of further 20 cases and molecular
      characterization of the parasite and its Wolbachia endosymbiont.
AB  - Recently, sporadic cases of subconjunctival Onchocerca infection have been
      reported in dogs in Greece and Hungary. Herein we report further cases from
      Greece and the results of the molecular analysis of Onchocerca sp. removed from
      Greek dogs and its Wolbachia endosymbionts. Twenty dogs of various breeds, 1-11
      years of age with subconjunctival onchocercosis (4 cases each in right or left
      eye, 12 cases in both eyes) were presented having similar manifestations.
      Periorbital swelling, exophthalmos, lacrimation, discharge, photophobia,
      conjunctival congestion, corneal edema, protrusion of the nictitating membrane,
      and subconjunctival granuloma or cyst formation were the most important clinical
      signs. After surgical excision of the periocular masses containing the worms, all
      animals recovered fully from onchocercosis. Based on the similarities of the
      clinical picture of the Greek and Hungarian cases, the similar morphology of the
      Greek and Hungarian isolates, and the identical sequences of the cytochrome
      oxidase gene of the filarial parasites and that of the 16S ribosomal RNA gene
      from their Wolbachia endosymbionts, the Onchocerca sp. isolated from dogs in
      Greece and Hungary appears to belong to the same species.

PMID- 14651885
TI  - Dung beetle activity and the development of trichostrongylid eggs into infective
      larvae in cattle faeces.
AB  - In the perspective to reduce the use of antiparasitic drugs, any interaction
      between the processes that control the development of parasite eggs into
      infective larval stages (L3) in dung and the activities of different dung
      breeding organisms becomes of interest. The objective of the present study was to
      determine whether dung beetle activity affected the development of parasite
      larvae in cattle dung. Faeces containing eggs of parasites (predominantly
      Cooperia spp.) were pooled according to high (250-600 epg) or low (approx. 100
      epg) egg counts. Experimental dung pats were formed for each category of faeces
      and to half of these pats, dung beetles (20 Aphodius rufipes, 20 A. scybalarius
      syn. rufus) were added and kept for 12 days at 21 degrees C (+/-1 degrees C) and
      90% RH (+/-5% RH). Beetles were then removed and the pats were divided in two
      where half the pat was incubated for an additional 12 days at 21 degrees C (+/-1
      degrees C) and 90% RH (+/-5% RH) and the other half was immediately analysed. A
      greater number of L3 were recovered from the dung subjected to beetle activity
      compared with control dung (P<0.001). However, following an additional 12 days
      incubation of the dung, similar numbers of L3 were recovered from beetle-affected
      dung with high egg counts, whereas there were significantly greater numbers of L3
      derived from the control dung (P<0.001). There was no significant difference in
      L3 recovery in the two categories of pats (i.e. high and low nematode egg
      counts). The results indicate that activity by Aphodius spp. in fresh dung can
      optimise conditions for nematode development to the infective larval stage if
      favourable environmental conditions prevail. Such synergistic effect may be due
      to the fact that dung beetles used in this study are dung dwellers, i.e. no
      substantial amount of the dung is removed or burrowed as these beetles feed, lay
      their eggs and the larval development takes place in brood chambers inside the
      dung.

PMID- 14651886
TI  - Larvicidal effects of several chemicals on Strongyloides infective larvae.
AB  - The larvicidal effects of 11 anthelmintics, 7 pesticides and 4 disinfectants were
      evaluated with infective larvae of Strongyloides papillosus (SPL) and
      Strongyloides venezuelensis (SVZ). The lethal concentrations against SPL and SVZ
      were found to be similar. Three chemicals (dichlorvos, levamisole and
      trichlorfon) showed highest larvicidal effects. The 50% lethal concentration
      (LC(50)) values for the three compounds against SPL larvae were 0.08, 0.24, and
      0.59 ppm, respectively.

PMID- 14651887
TI  - Validation of reference genes for transcription profiling in the salmon louse,
      Lepeophtheirus salmonis, by quantitative real-time PCR.
AB  - The salmon louse Lepeophtheirus salmonis, a marine ectoparasitic copepod that
      feeds on salmonids, cause huge financial losses in the aquaculture industry
      through fish mortality, reduced growth and therapeutic costs. Detailed knowledge
      about the salmon louse life cycle, at the functional molecular level, is of
      fundamental importance to evaluate alternative therapeutic or prophylactic
      strategies. In quantitative real-time PCR, a powerful technique in biological
      studies of differentially expressed genes, the transcription level of a regulated
      gene can be measured relative to an unregulated reference "housekeeping" gene. In
      the present study we validate candidate reference genes for transcription
      profiling throughout the life cycle of the salmon louse. Our results show that
      the structural ribosomal protein S20 (RPS20) and the translation elongation
      factor 1alpha (eEF1alpha) are valid as reference genes showing less than two fold
      variation in transcript levels. The frequently used reference gene glyceraldehyde
      3-phosphate dehydrogenase (GAPDH), however, is up to six fold regulated during
      the L. salmonis life cycle. Furthermore our results indicated that 18S RNA,
      although constitutively expressed, is not a convenient reference gene for
      relative quantification of most transcripts.

PMID- 14651888
TI  - Adsorption of Co, Ni, Cu, and Zn on hydrous manganese dioxide from complex
      electrolyte solutions resembling sea water in major ion content.
AB  - Adsorption of Co, Ni, Cu, and Zn onto a poorly crystalline hydrous manganese
      dioxide (delta-MnO2) has been studied in complex electrolyte solutions such as
      (a) 0.5 M NaCl+0.054 M MgCl2, (b) 0.5 M NaCl+0.028 M Na2SO4, and (c) artificial
      sea water prepared according to the standard literature method. These three
      solutions allow us to identify the specific effect of major cations, major
      anions, and the mixture of major cations and anions (including carbonate and
      bicarbonate) that is present in real sea water. The adsorption isotherm in major
      ion sea water at pH 7.25 indicates that while Co and Zn exhibit increases in
      adsorption with increase in concentration, Ni shows relatively poor adsorption,
      reaching a plateau at 0.075 mM concentration. The three trace metals (Co, Ni, and
      Zn) show Langmuirian behavior for adsorption at low concentration. It is
      generally observed that the fractional adsorption vs pH curve shifts to higher pH
      either in the presence of 0.054 M MgCl2 or in sea water. In the presence of 0.028
      M Na2SO4 the fractional adsorption vs pH curve remains almost unchanged with
      respect to a 0.5 M NaCl solution. The competitive adsorption of one trace metal
      in the presence of other three in major ion sea water indicates that this
      phenomenon is more predominant with Ni and Zn than with Co and Cu.

PMID- 14651889
TI  - Adsorption of Co2+, Ni2+, Cu2+, and Zn2+ onto amorphous hydrous manganese dioxide
      from simple (1-1) electrolyte solutions.
AB  - The adsorption of Co2+, Ni2+, Cu2+, and Zn2+ onto amorphous hydrous manganese
      dioxide (delta-MnO2) has been studied using two methods, viz., isotherms at
      constant pH in the presence of buffer solution and pH variation in the absence of
      buffer solution from a fixed metal ion concentration. While the adsorption
      isotherm experiments were carried out in 0.5 M NaCl only, pH variation or batch
      titration experiments were carried out in 0.5 M NaCl, 0.01 M NaCl, and 0.01 M
      KNO3 solutions. The complex nature of adsorption isotherms at constant pH values
      indicates that adsorption of all the cations is non-Langmuirian (Freundlich) and
      takes place on the highly heterogeneous oxide surface with different binding
      energies. The proton stoichiometry derived from isotherms at two close pH values
      varies between 0.3 and 0.8. The variation of fractional adsorption with pH
      indicates that the background electrolyte solution influences the adsorption of
      cations through either metal-like or ligand-like complexes with Cl-, the former
      showing a low adsorption tendency. The proton stoichiometry values derived from
      the Kurbatov-type plot varies not only with the electrolyte solution but also
      with the adsorbate/adsorbent ratio. The variation of fractional adsorption with
      pH can be modeled either with the formation of the SOM+ type or with a
      combination of SOM+ and SOMOH type complexes, depending upon the cation and
      electrolyte medium. The equilibrium constants obtained from Kurbatov-type plots
      are found to be most suitable in these model calculations. Adsorption calculated
      on the basis of ternary surface metal-chlorocomplex formation exhibits very low
      values.

PMID- 14651890
TI  - Effect of layer charge density on orientation and aggregation of a cationic laser
      dye incorporated in the interlayer space of montmorillonites.
AB  - Effect of layer charge density of clay on the orientation and aggregation state
      of a laser dye, oxazine 4, in dye/clay complexes was investigated using a series
      of layer-charge-controlled montmorillonites as host materials. By the combination
      of polarized UV-vis spectroscopy and powder X-ray diffraction methods, it was
      revealed that the higher layer charge caused the formation of higher-order H
      aggregates with the molecular axis nearly perpendicular to the silicate layer,
      and that the basal spacing was mostly governed by the degree of dye aggregation.

PMID- 14651891
TI  - High dispersion and electrocatalytic properties of platinum nanoparticles on
      graphitic carbon nanofibers (GCNFs).
AB  - Highly dispersed platinum nanoparticles were electrodeposited on graphitic carbon
      nanofibers (GCNFs) by cyclic voltammetry (CV) in 7.7 mM H2PtCl6+0.5 M HCl aqueous
      solutions. The graphitic carbon nanofibers (GCNFs) used in this paper were grown
      directly on a graphite disk by chemical vapor deposition (CVD). The micrographs
      and element composition of Pt/GCNFs/graphite electrode were characterized by
      scanning electron microscopy (SEM) and electron diffraction spectroscopy (EDS).
      The electrocatalytic properties of Pt/GCNFs/graphite electrode for methanol
      oxidation have been investigated by CV and excellent electrocatalytic activity
      can be observed even at very low platinum loading (md=8.79 microg cm(-2)). The
      highest mass activity (MA) for methanol oxidation reaches 323 Ag(-1) when
      Pt/GCNFs/graphite electrode was cycled at a sweep rate of 50 mVs(-1) by CV in 2 M
      CH3OH+1 M H2SO4 aqueous solutions. This may be attributed to the small particle
      size and high dispersion of platinum particles coated on GCNFs and shows good
      potential application in direct methanol fuel cell (DMFC). Additionally, the long
      term cycling stability of platinum catalysts was also investigated.

PMID- 14651892
TI  - Adsorption of metal halides from ethanol solutions by a 3-n
      propylpyridiniumsilsesquioxane chloride-coated silica gel surface.
AB  - 3-n-propylpyridiniumsilsesquioxane chloride polymer, abbreviated as SiPy+Cl-, was
      used to coat a porous silica gel, SiO2, surface to form the chemically modified
      solid SiO2/SiPy+Cl-. The resulting polymer film was well adhered to the surface
      and presented an ion exchange capacity of 0.74 mmol g(-1). Metal halides, MClz
      [M=Fe(III), Cu(II), and Zn(II)], were adsorbed by the modified solid from ethanol
      solutions as neutral species by forming the surface anionic complexes described
      by the equation: mSiO2/SiPy+Cl-+ MClz <=> (SiO2/SiPy+)m[MCl(z+m)]m-, where the
      [MCl(z+m)]m- species adsorbed on the surface are FeCl4-, ZnCl4(2-), and CuCl4(2
      ). Accurate estimates of the specific sorption capacities and the heterogeneous
      stability constants of the immobilized metal complexes were determined with the
      aid of computational procedures.

PMID- 14651893
TI  - Modeling the adsorption of Cd(II) onto goethite in the presence of citric acid.
AB  - The adsorption of cadmium onto goethite in the presence of citric acid was
      measured as a function of pH and cadmium concentration at 25 degrees C.
      Potentiometric titrations were also performed on the system. Cadmium adsorption
      onto goethite was enhanced above pH 4 in the presence of 50 microM, 100 microM
      and 1 mM citric acid. While there was little difference between the enhancements
      caused by 50 and 100 microM citric acid below pH 6, above pH 6 further
      enhancement is seen in the presence of 100 microM citric acid. When 1 mM citric
      acid was present, the enhancement of cadmium adsorption was greater below pH 6,
      with increased Cd(II) adsorption down to pH 3.5. However, above pH 6, 1 mM of
      citric acid caused slightly less enhancement than the lower citric acid
      concentrations. ATR-FTIR spectra of soluble and adsorbed citrate-cadmium species
      were measured as a function of pH. At pH 4.6 there was very little difference
      between the ternary Cd(II)-citric acid-goethite spectrum and the binary citric
      acid-goethite spectrum. However, spectra of the ternary system at pH 7.0 and 8.7
      indicated the presence of additional surface species. Further analysis of the
      spectra suggested that these were metal-ligand outer-sphere complexes. Data from
      the adsorption experiments and potentiometric titrations of the ternary Cd(II)
      citric acid-goethite system were fitted by an extended constant-capacitance
      surface complexation model. The spectroscopic data were used to inform the choice
      of surface species. Three reactions in addition to those for the binary Cd(II)
      goethite and citric acid-goethite systems were required to describe all of the
      data. They were [formula in text], [formula in text], and [formula in text].
      Neither the spectroscopy nor the modeling suggested the formation of a ternary
      inner-sphere complex or a surface precipitate under the conditions used in this
      study.

PMID- 14651894
TI  - Sorption of phenols from water in column systems using surfactant-modified
      montmorillonite.
AB  - The sorption of phenol, m-nitrophenol (m-NP), and o-cresol from water onto
      montmorillonite modified with cetyltrimethylammonium bromide (CTAB) in a column
      was studied. The sorption isotherms were fitted by the Langmuir equation. Column
      experiments were performed at 25 degrees C to determine the breakthrough curves
      at different flow rates, feed sorbate concentrations, and bed lengths. It was
      shown that the proposed constant-pattern wave approach with the Langmuir model
      could well describe the breakthrough curves. The time required when the effluent
      concentration reached half of the feed concentration (t(1/2)) decreased with
      increasing feed flow rate, but the mass transfer coefficient (KLa) increased. In
      addition, an increase in feed sorbate concentration led to a decrease of both
      values of t(1/2) and KLa. The effect of axial dispersion on breakthrough dynamics
      in these sorption systems was finally discussed.

PMID- 14651895
TI  - Kinetics of particle deposition in the oblique impinging jet cell.
AB  - A new oblique impinging-jet (OBIJ) cell was developed, suitable for colloid
      deposition studies at various interfaces. In contrast to previously used
      orthogonal cells, the OBIJ construction makes possible direct microscope
      observations of particle deposition on nontransparent substrates. The cell
      performance was tested by studying kinetics of polystyrene latex particle
      deposition on mica. Two limiting cell configuration were used in the experiments:
      (i) the lower position (inverted microscope observation of substrate surface
      through air) and (ii) the upper position (observation of the substrate surface
      with adsorbed particles through the suspension layer). The dependence of local
      mass transfer rate (particle flux) on the position over the substrate surface was
      studied for various flow Reynolds numbers. It was demonstrated that deposition
      rate attained maximum at the flow stagnation point whose position was dependent
      on Re number. Moreover, it was shown that the local flux decreased at much slower
      rate when moving in the downstream direction, than for previously used impinging
      jet cells. Consequently, the area of uniform transport conditions was larger,
      enabling more precise determination of the limiting particle flux at the
      stagnation-point. The dependence of the flux on Re number was systematically
      studied for various ionic strength of the suspension. It was demonstrated, in
      accordance with previous results for the ordinary impinging-jet, that the flux
      increased significantly for low ionic strength and high Re number. This
      phenomenon, referred to as the inverse salt effect, was interpreted in terms of
      the convective diffusion theory. The governing transport equation originating
      from this theory was solved numerically, for the region near the stagnation
      point, using the finite-difference method. These numerical solutions were used
      for nonlinear fitting of the flow intensity parameter dependence on the Re
      number. In this way the flow field in the vicinity of the stagnation point was
      fully characterized. It was concluded that the new cell can be exploited as an
      effective experimental tool for colloid deposition studies on various substrates.

PMID- 14651897
TI  - Orientational defects near colloidal particles in a nematic liquid crystal.
AB  - We study the interaction between a surface-anchoring colloidal particle and a
      liquid-crystalline host, and in particular the formation of orientational defects
      near the particle. A mean-field theory based on the nonlocal Marrucci-Greco
      nematic potential is used to represent molecular interactions in an inhomogeneous
      orientational field. An evolution equation for the molecular configuration tensor
      is solved numerically whose steady state minimizes the total free energy of the
      system. With strong homeotropic anchoring on the particle surface, three types of
      solutions may appear depending on initial conditions and particle size: Saturn
      rings, satellite point defects, and polar rings. The Saturn ring remains stable
      on micrometer-sized particles, contrary to previous calculations but consistent
      with experiments. A phase diagram is constructed for the three regimes. Based on
      the free energy, the most stable state is the Saturn ring for smaller particles
      and the satellite defect for larger ones.

PMID- 14651896
TI  - Grafting of poly(ethylene oxide) to the surface of polyaniline films through a
      chlorosulfonation method and the biocompatibility of the modified films.
AB  - Poly(ethylene oxide) (PEO) could be grafted on the surface of polyaniline (PANI)
      films by chlorosulfonating the films with chlorosulfonic acid followed by
      reacting the modified films with PEO in a pyridine solution. The modified PANI
      films were examined by X-ray photoelectron spectroscopy and water droplet contact
      angles. The surface of the PEO grafted to hydrophobic PANI films became
      hydrophilic and the amounts of bovine serum albumin and human blood plasma
      platelet adsorbed onto it were decreased by more than 80%. For comparison
      purposes, and because the water wetting angle can be used as a measure of
      biocompatibility, wetting angle experiments have been also carried out for
      Pluronic triblock copolymer grafted to PANI and PEO or Pluronic molecules
      entrapped on the surfaces of PANI films. PANI was selected as substrate because
      one can easily change its surface properties by PEO grafting and because being
      conductive can be used as a sensor.

PMID- 14651898
TI  - Regular patterns generated by self-organization of ammonium-modified polymer
      nanospheres.
AB  - Macroscopic regular stripe-crack patterns have been observed in the course of
      drying the aqueous suspensions of ammonium-modified polymer nanospheres. These
      forms emerged because the evaporation of dispersed water and self-assembly of
      nanospheres originates shrinkage during drying the aqueous suspensions. The
      drying condition plays an important role as well as the nature of the ammonium
      modified polymer nanospheres for the stripe-crack pattern formation. By means of
      the vertical deposition method, directional stripe-crack patterns have been
      achieved in the macroscopic scale. Surprisingly, we have still noted an
      interesting secondary stripe pattern occurred spontaneously on the stripes.

PMID- 14651899
TI  - Forces between a rigid probe particle and a liquid interface. III. Extraction of
      the planar half-space interaction energy E(D).
AB  - The deformation of a liquid drop (radius R0) under the probe particle (radius a)
      greatly complicates the interpretation by atomic force microscopy. For rigid
      interfaces, F(DeltaX) can be directly related to the interaction energy E(D) per
      unit area between planar half-spaces of probe material and drop material across a
      thickness D of the liquid medium by the Derjaguin approximation, [formula in
      text], where D(0) is the intersurface separation distance on the line of the
      centers of the bodies and DeltaX0 is a constant set by the somewhat arbitrary
      choice of origin for the separation distance DeltaX between the stage on which
      the drop rests and the lowest point on the probe particle. The problem of
      absolute intersurface separation distance is common to all surface force
      measurement techniques. For rigid interfaces, DeltaX0 may be established by
      bringing the surfaces into close (essentially hard) contact and making
      measurements in the constant compliance regime. For deformable interfaces, this
      is not possible and a general method of extracting the absolute separation
      distance has yet to be devised. In this paper we discuss a general algorithm for
      extracting E(D+DeltaX0) from F(DeltaX) data. We apply the method to constructed
      data to investigate the effect of data noise and to a set of real data for a
      sessile tetradecane droplet in water with an anionic surfactant and a bare silica
      probe.

PMID- 14651901
TI  - Preparation of Gd2O3:Yb,Er and Gd2O2S:Yb,Er infrared-to-visible conversion
      phosphor ultrafine particles using an emulsion liquid membrane system.
AB  - Upconverting phosphor fine particles (Gd2O3:Yb,Er and Gd2O2S:Yb,Er) have been
      prepared, using an emulsion liquid membrane (ELM, water-in-oil-in-water (W/O/W)
      emulsion) system. The composite Gd-Yb-Er oxalate particles obtained in the ELM
      system were mainly 20-60 nm in size, together with a smaller amount of
      submicrometer-sized spherical particles. Nanometer-sized Gd2O3:Yb,Er and
      Gd2O2S:Yb,Er particles were obtained by calcination in air and in sulfur
      atmosphere, respectively, of the precursor oxalate particles prepared in the ELM
      system. Upconversion emissions (red and green) were obtained from the Gd2O3:Yb,Er
      and Gd2O2S:Yb,Er particles prepared in the ELM system under infrared excitation
      (lambdaex=980 nm) via a two-photon process. Upconversion phosphor fine particles,
      about 50 nm in diameter, may be applied to the luminescent reporter material for
      the detection of the targeted analyte in immunoassays or DNA assays.

PMID- 14651900
TI  - Water-dispersible tryptophan-protected gold nanoparticles prepared by the
      spontaneous reduction of aqueous chloroaurate ions by the amino acid.
AB  - The synthesis of water-dispersible amino-acid-protected gold nanoparticles by the
      spontaneous reduction of aqueous chloroaurate ions by tryptophan is described.
      Water-dispersible gold nanoparticles may also be obtained by the sequential
      synthesis of the gold nanoparticles by borohydride reduction of chloroauric acid
      followed by capping with tryptophan. Comparison of the proton NMR spectroscopic
      signatures from the tryptophan-protected gold nanoparticles obtained by the two
      processes indicated that the indole group in tryptophan is responsible for
      reduction of the aqueous chloroaurate ions. The reduction of the metal ions is
      accompanied by oxidative polymerization of the indole group of the tryptophan
      molecules and, consequently, some degree of cross-linking of the gold
      nanoparticles.

PMID- 14651902
TI  - Surface modification of oxidic nanoparticles using 3
      methacryloxypropyltrimethoxysilane.
AB  - Tin oxide, antimony-doped tin oxide (ATO), and silica nanosized particles in
      aqueous dispersion were reacted with various amounts of 3
      methacryloxypropyltrimethoxysilane (MPS). The kinetics were followed by 29Si NMR
      and the products were analyzed by FTIR and 29Si NMR. The kinetic experiments on
      ATO and silica revealed that the hydrolysis is the rate-determining step in these
      reactions. The reaction of MPS with the particles is favored over the
      homocondensation of MPS. Quantitative analysis using FTIR revealed that the
      amount of MPS grafted onto the tin oxide and silica particles is limited to the
      amount needed to fill one monolayer. For ATO the maximum amount of grafted MPS
      was only 50-70% of the amount that is needed for a closed monolayer. The MPS
      molecules are for the most part oriented parallel to the oxide surface, and a
      hydrogen bond between the MPS-carbonyl and the oxide is formed.

PMID- 14651903
TI  - Settling of paraffin crystals in cooled middle distillate fuels.
AB  - The mechanism of action of additives that control the sedimentation of paraffin
      crystals after their crystallization in model diesel oil has been studied by
      means of a new experimental approach. The chemical analysis of the crystals and
      detailed measurements of the sedimentation phenomenon give new insights into this
      complex process. Thus, the wax antisettling additives used for preventing wax
      crystal sedimentation adsorb at the surfaces of wax particles and provide them
      with enhanced colloidal stability. The settling rate is not related to the size
      of the crystals or the viscosity of the liquid medium, but to the ability of the
      additives to prevent the aggregation of wax crystals. The reported methodology
      makes it possible to investigate the fundamental mechanisms, but also to evaluate
      structure-activity relationships of the various additives used in the petroleum
      industry.

PMID- 14651904
TI  - A low-temperature, soft chemistry method for the synthesis of zirconia
      nanoparticles in thermally evaporated fatty amine thin films.
AB  - We demonstrate the synthesis of zirconia nanoparticles in a lipid matrix by a
      simple, low temperature beaker-based process. This is accomplished by
      electrostatic entrapment of ZrF6(2-) ions within thermally evaporated
      octadecylamine (ODA) thin films followed by the low-temperature in situ
      hydrolysis of the entrapped metal ion complexes. The zirconia particles thus
      formed were of the monoclinic phase and were fairly monodisperse with particles
      of average size 40 nm. The zirconia crystallites appeared to exhibit preferred
      orientation indicating epitaxial growth of the crystals within the lipid matrix.
      The formation of zirconia nanoparticles in the lipid matrix was investigated
      using quartz crystal microgravimetry (QCM), optical absorption spectroscopy, X
      ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and
      X-ray diffraction (XRD) techniques.

PMID- 14651905
TI  - Reaction rates of heavy metal ions at goethite: relaxation experiments and
      modeling.
AB  - In the present paper we extend our theory that calculates the fastest reaction
      step observable in suspensions containing charged microcrystals and heavy metal
      cations. The calculation requires the solution of the nonlinear Poisson-Boltzmann
      equation for nonsymmetric electrolytes plus the Nernst-Planck equation for
      transport of ions in electric fields. We find that the diffusional transport of
      ions to and from the surface is the rate-limiting process for our experimentally
      observed maximum rates. At low pH and low metal ion concentration the diffusion
      of metal ions is the rate-limiting step, whereas for high pH and high metal ion
      concentration the diffusion of the solvated protons controls the overall
      relaxation rate. The validity of this theory is checked for the reactions of Pb2+
      and Cd2+ with goethite by means of pressure jump relaxation experiments over a
      wide range of temperature and pH. In all cases we observe fast processes
      (relaxation in the range of 10(3) s(-1)) in quantitative agreement with the
      theory, followed by slower processes, most probably caused by diffusion into the
      interior of the porous microcrystals.

PMID- 14651906
TI  - Determination of the surface characteristics of particulate fillers by inverse
      gas chromatography at infinite dilution: a critical approach.
AB  - CaCO3 fillers were investigated by inverse gas chromatography (IGC) to determine
      the dispersion component of their surface tension as well as their acid-base
      character. Because of the high energy of the filler surface, it readily adsorbs
      water, thus the parameters measured by IGC depend on the conditioning
      temperature, as well as on the measurement conditions. As a consequence, the
      determined surface characteristics are not material constants; different fillers
      or the effect of coating can be compared only under standard conditions. The use
      of the same conditioning and measurement temperature eliminates the effect of
      measurement time. Under appropriate standard conditions the acid-base
      characteristics of the filler can be determined reliably. However, the accuracy
      of the determination and the value of the derived parameters depend very much on
      the selected approach and on the acid-base constants used for the probe
      molecules. A critical analysis of the approaches used in the current literature
      pointed out those that yield the most reasonable and accurate values. The results
      prove that the surface of CaCO3 is strongly basic in character. Coating
      significantly reduces basicity. Surprisingly, the filler coated with an amount of
      stearic acid resulting in minimum surface tension showed relatively strong
      acidity, which indicates a coating exceeding monolayer coverage and/or the uneven
      distribution of the surfactant on the surface.

PMID- 14651907
TI  - Influence of phytohormones on polar and hydrophobic parts of mixed phospholipid
      monolayers at water/air interface.
AB  - Surface parameters--the limiting area, collapse pressure, and compressibility
      modulus for monolayers of phospholipids containing a determined hydrophobic part
      (16:0) but different polar parts (PPL) and a determined polar part (PC) but
      different fatty acids (HPL), characteristic of nonembryogenic (NE) and
      embryogenic (E) winter wheat calli--were evaluated at 15 degrees C. These
      parameters were dependent on the kind of hydrophilic group and the size of the
      hydrophobic part of phospholipids. In the case of PPL, higher values of Alim and
      picoll were noticed for NE phospholipids. In the case of HPL, lower Alim and
      higher picoll were detected for NE than for E monolayers. All investigated
      phospholipid systems stimulated the adsorption of phytohormones from the water
      subphase. The influence of phytohormones of anionic (IAA, 2-4-D), cationic
      (kinetin, zeatin), and nonionic character (zearalenone) was examined. It appeared
      that the surface activity of phytohormones depended strongly on the kind of
      tissue from which the phospholipid mixture was extracted and, in a lesser degree,
      on their charge. In PPL systems with a determined hydrophobic part (16:0), no
      great differences in phytohormone influence on NE and E monolayers were observed
      (except of IAA). The greatest phytohormone influence on NE monolayers in HPL
      systems was related to the structure of the hydrophobic part of phospholipids.
      IAA, the most active (with the highest Alim values) among the phytohormones
      examined, influenced both HPL and PPL monolayers. This indicated the interactions
      of IAA with polar groups of phospholipids. Phytohormones also changed the
      monolayer stability against collapse process and the direction of changes
      depended on the kind of tissue (embryogenic or nonembryogenic).

PMID- 14651908
TI  - Ordered droplet formation by thin polymer film dewetting on a stripe-patterned
      substrate.
AB  - The dewetting process of thin polystyrene (PS) film on flat and stripe-patterned
      substrates is presented. Different dewetting processes were observed when the
      thin PS films annealed at above the glass transition temperature on these
      different kinds of substrates. The final dewetting on the flat substrate led to
      formation of polygonal liquid droplets, while on the stripe-patterned substrate,
      the droplets were observed to align at the centers of the stripes. A possible
      explanation for the dewetting process on the stripe-patterned substrate is
      proposed.

PMID- 14651909
TI  - Probing with a laser sheet the contact angle distribution along a contact line.
AB  - An optical method for probing contact angle distribution along contact lines of
      any shape using a laser sheet is proposed. This method is applied to a dry patch
      formed inside a film flowing along an inclined plane, both liquid and solid being
      transparent. Falling normally to the plane, a laser sheet cuts the contact line
      and is moved along this line. Distortions of the sheet trace observed on a screen
      put below the plane allow us to extract the contact angle distribution and the
      local line inclination along the line. Our results show that the contact angle
      around a dry patch is nearly constant and equal to the static advancing angle, at
      least when the evolution of its shape is followed for increasing flow rates. This
      supports a model of dry patch shape recently proposed by Podgorski and co
      workers. Preliminary results obtained for decreasing flow are also qualitatively
      observed.

PMID- 14651910
TI  - Advancing contact lines on chemically patterned surfaces.
AB  - We report an experimental investigation on advancing contact lines of large drops
      spreading on chemically patterned surfaces. The model substrates were prepared
      using microphotolithography allowing precise control of the position and the size
      of the wettability patterns. Experiments were performed exploring different
      surface geometries: from ordered to disordered fields of defects and from low to
      high surface densities. The shape of the contact line between two isolated
      defects was investigated as a function of the distance. Portions of the contact
      line on the defects and on the matrix were studied during spreading experiments
      and were related to the apparent contact angles measured from the final thickness
      of the drops. A modified Cassie equation based on the line fraction of defects is
      proposed.

PMID- 14651911
TI  - Effect of interfacial tension on the dynamic behavior of droplet formation during
      microchannel emulsification.
AB  - Microchannel (MC) emulsification is a novel technique for producing monodisperse
      emulsions. In this study, we investigated the effect of interfacial tension on
      the dynamic behavior of droplet formation with various surfactant concentrations.
      Interfacial tension did not affect the resultant droplet diameter in lower flow
      velocity ranges, but it did affect the time-scale parameters. These results were
      interpreted using the droplet formation mechanism reported in our previous study.
      At surfactant concentrations below 0.3%, the emulsification behavior was differed
      from that at higher surfactant concentrations. An analysis of diffusional
      transfer indicated that dynamic interfacial tension affects the emulsification
      behavior at lower surfactant concentrations. Dynamic interfacial tension that
      exceeded the equilibrium value led to a shorter detachment time. This resulted in
      stable droplet formation of monodispersed emulsions by spontaneous
      transformation, even at flow velocities above the predicted critical flow
      velocity. A previous study predicted that the droplet formation would become
      unstable and polydispersed larger droplets would form over critical flow
      velocity. Wetting of the MC with the dispersed phase at lower surfactant
      concentrations induced formation of larger polydispersed droplets at high flow
      velocities.

PMID- 14651912
TI  - Ionic diffusion through thick matrices of charged particles.
AB  - Ionic diffusion through thick beds of charged matrices occurs in many fields.
      Ionic transport is driven by electrochemical potential gradient, i.e., it is a
      combined result of chemical potential gradient and electrical potential gradient.
      To clarify a number of unexplained observations, the steady state diffusion of
      NaCl and LiCl solutions through 76-mm-thick Na- and Li-bentonite pastes, reported
      by Dutt and Low, has been critically analyzed. The analyses showed that in the
      pastes the concentrations of M+ ions are much higher than those of Cl- ions. The
      phenomenological diffusivity of cation and anion are the same. Decomposition of
      the phenomenological ion flux into parts due to chemical and electrical potential
      gradients shows that the chemical diffusivity of the anion is higher than its
      phenomenological diffusivity. Cations are the other way round. The electric
      potential gradient created by the concentration gradient of ions causes these
      changes. Phenomenological and chemical diffusivity are concentration-dependent
      and are related by an equation of the type Y=A-B square root of c, where A and B
      are constants and c is the molar concentration of the ion. This relation is due
      to Coulomb's law modeling of ion-ion interaction. The above inferences have
      bearing on the fields of ground water contamination, durability of cement-based
      materials, construction of clay-lined waste landfills, and construction of
      nuclear deposits.

PMID- 14651913
TI  - A method for determining electrophoretic and electroosmotic mobilities using AC
      and DC electric field particle displacements.
AB  - We have developed a method for measuring the electrophoretic mobility of
      submicrometer, fluorescently labeled particles and the electroosmotic mobility of
      a microchannel. We derive explicit expressions for the unknown electrophoretic
      and the electroosmotic mobilities as a function of particle displacements
      resulting from alternating current (AC) and direct current (DC) applied electric
      fields. Images of particle displacements are captured using an epifluorescent
      microscope and a CCD camera. A custom image-processing code was developed to
      determine image streak lengths associated with AC measurements, and a custom
      particle tracking velocimetry (PTV) code was devised to determine DC particle
      displacements. Statistical analysis was applied to relate mobility estimates to
      measured particle displacement distributions.

PMID- 14651914
TI  - Extension of the surfactant bridge model for the electrorheological effects of
      surfactant-activated suspensions.
AB  - Surfactants influence the electrorheological (ER) response in two ways. At low
      surfactant concentrations, they enhance the ER response by enhancing the particle
      polarizability; at high concentrations, the response degrades (nonlinear ER
      response). The nonlinear ER behavior arises from the formation of surfactant
      bridges between the particles at high surfactant concentrations. A surfactant
      bridge model was introduced to explain the nonlinear behavior (tau0 proportional
      to En, n approximately 1) of surfactant-activated ER suspensions when surfactant
      bridges were formed between the particles. Here, the surfactant bridge model is
      extended for the prediction of both the linear and nonlinear ER behaviors of
      surfactant-activated ER suspensions over the low and high surfactant
      concentrations (for Brij 30, from 0 to 7 wt%), regardless of the formation of
      surfactant bridges between the particles. For 20 wt% neutral alumina suspensions
      in silicone oil activated by Brij 30, the predicted ER behaviors show almost the
      same Brij 30 concentration and electric field strength dependence. It predicts
      the linear E2 dependence of the ER response at low surfactant concentrations and
      the nonlinear ER behavior at high surfactant concentrations. Also, the estimated
      yield stresses show fairly good agreement with the experimental data.

PMID- 14651915
TI  - Electrokinetics of the amphifunctional metal/electrolyte solution interface in
      the presence of a redox couple.
AB  - Double layers (DL) at amphifunctionally electrified interfaces, such as that of
      an oxidized metal in an aqueous electrolyte solution, arise from coupling between
      ionic and electronic surface-charging processes. The electronic component enters
      the double-layer formation in the well-known situation where a potential is
      externally applied. In that case, the DL is fully or partly polarized depending
      on the possibility of interfacial electron transfer, that is, a faradaic process.
      This paper reports on the conjunction of the chemical/electrochemical processes
      at the interface in the case where the solution contains a redox-active couple.
      This makes it possible to polarize/depolarize a DL without invoking any external
      circuit. Streaming potential data obtained for the gold/(Fe(CN)6(3-)/Fe(CN)6(4-),
      KNO3) electrolyte interface are analyzed in terms of a recently developed theory
      which takes into account reversible bipolar faradaic depolarization, the inherent
      nonlinearity of the lateral field, and the effects of flow on the rate of the
      faradaic reactions. It appears that the theory largely overestimates the bipolar
      currents, leading to physically unrealistic zeta-potentials. A careful analysis
      of monopolar voltammetric data reveals quasi-reversible behavior of the redox
      couple under the typical convective conditions and electrolyte compositions met
      in electrokinetic experiments. Inclusion of reduced reversibility (the extent of
      which is position-dependent under the streaming-potential measurement conditions)
      leads to a consistent set of zeta-potentials which compare well to the values for
      the background electrolyte.

PMID- 14651916
TI  - Destabilizing effect of time-dependent oblique magnetic field on magnetic fluids
      streaming in porous media.
AB  - The present work studies Kelvin-Helmholtz waves propagating between two magnetic
      fluids. The system is composed of two semi-infinite magnetic fluids streaming
      throughout porous media. The system is influenced by an oblique magnetic field.
      The solution of the linearized equations of motion under the boundary conditions
      leads to deriving the Mathieu equation governing the interfacial displacement and
      having complex coefficients. The stability criteria are discussed theoretically
      and numerically, from which stability diagrams are obtained. Regions of stability
      and instability are identified for the magnetic fields versus the wavenumber. It
      is found that the increase of the fluid density ratio, the fluid velocity ratio,
      the upper viscosity, and the lower porous permeability play a stabilizing role in
      the stability behavior in the presence of an oscillating vertical magnetic field
      or in the presence of an oscillating tangential magnetic field. The increase of
      the fluid viscosity plays a stabilizing role and can be used to retard the
      destabilizing influence for the vertical magnetic field. Dual roles are observed
      for the fluid velocity in the stability criteria. It is found that the field
      frequency plays against the constant part for the magnetic field.

PMID- 14651917
TI  - Diffusiophoretic mobility of charged porous spheres in electrolyte gradients.
AB  - The diffusiophoretic motion of a polyelectrolyte molecule or charged floc in an
      unbounded solution of a symmetrically charged electrolyte with a uniform
      prescribed concentration gradient is analytically studied. The model used for the
      particle is a porous sphere in which the density of the hydrodynamic frictional
      segments, and therefore also that of the fixed charges, is constant. The
      electrokinetic equations which govern the electrostatic potential profile, the
      ionic concentration distributions (or electrochemical potential energies), and
      the fluid velocity field inside and outside the porous particle are linearized by
      assuming that the system is only slightly distorted from equilibrium. Using a
      regular perturbation method, these linearized equations are solved for a charged
      porous sphere with the density of the fixed charges as the small perturbation
      parameter. An analytical expression for the diffusiophoretic mobility of the
      charged porous sphere in closed form is obtained from a balance between its
      electrostatic and hydrodynamic forces. This expression, which is correct to the
      second order of the fixed charge density of the particle, is valid for arbitrary
      values of kappaa and lambdaa, where kappa is the reciprocal of the Debye
      screening length, lambda is the reciprocal of the length characterizing the
      extent of flow penetration inside the particle, and a is the particle radius. Our
      result to the first order of the fixed charge density agrees with the
      corresponding solution for the electrophoretic mobility obtained in the
      literature. In general, the diffusiophoretic mobility of a porous particle
      becomes greater as the hindrance to the diffusive transport of the solute species
      inside the particle is more significant.

PMID- 14651918
TI  - Competitive adsorption of bacteriophage T4 lysozyme stability variants at
      hydrophilic glass surfaces.
AB  - The competitive adsorption behavior exhibited by the wild-type T4 lysozyme and
      two of its structural stability variants was studied by 125I radioisotope
      labeling. The mutant lysozymes were produced by substitution of the isoleucine
      residue at position 3 in the wild type with a tryptophan residue, resulting in a
      protein with lower structural stability, or with a cysteine residue, resulting in
      a protein with higher structural stability. Adsorption kinetics were recorded for
      binary protein mixtures in contact with a clean glass surface, in which one
      variant had been radiolabeled and the other had not. All pair permutations were
      tested. The kinetic data show that in instances in which exchange reactions
      between adsorbed protein and dissolved protein occur, they occur such that more
      stable variants are removed from the surface by less stable variants. The less
      stable proteins thus exhibited an advantage in competitive adsorption over the
      more stable proteins, in these tests.

PMID- 14651919
TI  - Electrophoretic mobility of a soft particle in a salt-free medium.
AB  - A theory is presented for the electrophoretic mobility mu of dilute spherical
      soft particles (i.e., polyelectrolyte-coated particles) in salt-free media
      containing only counterions. As in the case of other types of particles (rigid
      particles and liquid drops) in salt-free media, there is a certain critical value
      of the particle charge separating two cases, the low-surface-charge case and the
      high-surface-charge case. For the low-charge case, the mobility is proportional
      to the particle charge and coincides with that of a soft particle in an
      electrolyte solution in the limit of very low electrolyte concentrations kappa-
      >0 (Huckel's limit), where kappa is the Debye-Huckel parameter. For the high
      charge case, however, mu becomes essentially constant, independent of the
      particle charge, due to the counterion condensation effect.

PMID- 14651920
TI  - Neural progenitor genes. Germinal zone expression and analysis of genetic overlap
      in stem cell populations.
AB  - The identification of the genes regulating neural progenitor cell (NPC) functions
      is of great importance to developmental neuroscience and neural repair.
      Previously, we combined genetic subtraction and microarray analysis to identify
      genes enriched in neural progenitor cultures. Here, we apply a strategy to
      further stratify the neural progenitor genes. In situ hybridization demonstrates
      expression in the central nervous system germinal zones of 54 clones so
      identified, making them highly relevant for study in brain and neural progenitor
      development. Using microarray analysis we find 73 genes enriched in three neural
      stem cell (NSC)-containing populations generated under different conditions. We
      use the custom microarray to identify 38 "stemness" genes, with enriched
      expression in the three NSC conditions and present in both embryonic stem cells
      and hematopoietic stem cells. However, comparison of expression profiles from
      these stem cell populations indicates that while there is shared gene expression,
      the amount of genetic overlap is no more than what would be expected by chance,
      indicating that different stem cells have largely different gene expression
      patterns. Taken together, these studies identify many genes not previously
      associated with neural progenitor cell biology and also provide a rational scheme
      for stratification of microarray data for functional analysis.

PMID- 14651921
TI  - FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel
      role of Notch in organ development.
AB  - FGF10 plays an important role in the morphogenesis of several tissues by control
      of mesenchymal-to-epithelial signaling. In the pancreas, mesenchymal FGF10 is
      required to maintain the Pdx1-expressing epithelial progenitor cell population,
      and in the absence of FGF10 signaling, these cells fail to proliferate. Ectopic
      expression of FGF10 in the pancreatic epithelium caused increased proliferation
      of pancreatic progenitor cells and abrogation of pancreatic cell differentiation
      of all cell types. A hyperplastic pancreas consisting of undifferentiated cells
      expressing Pdx1, Nkx6.1, and cell adhesion markers normally characterizing early
      pancreatic progenitor cells resulted. Differentiation was attenuated even as
      proliferation of the pancreatic cells slowed during late gestation, suggesting
      that the trophic effect of FGF10 was independent of its effects upon cell
      differentiation. The FGF10-positive pancreatic cells expressed Notch1 and Notch2,
      the Notch-ligand genes Jagged1 and Jagged2, as well as the Notch target gene
      Hes1. This activation of Notch is distinct from the previously recognized
      mechanism of lateral inhibition. These data suggest that FGF10 signaling serves
      to integrate cell growth and terminal differentiation at the level of Notch
      activation, revealing a novel second role of this key signaling system during
      pancreatic development.

PMID- 14651922
TI  - Cloning and characterization of Xenopus Id4 reveals differing roles for Id genes.
AB  - We have identified Xenopus Id4, a member of the Id (inhibitor of
      differentiation/DNA binding) class of helix-loop-helix proteins. Id factors
      dimerize with general bHLH factors, preventing their interaction with tissue
      specific bHLH factors, to inhibit premature differentiation. The presence of
      several Id proteins could reflect simple redundancy in function, or more
      interestingly, might suggest different activities for these proteins. During
      embryonic development, Xenopus Id4 is expressed in a number of neural tissues,
      including Rohon-Beard neurons, olfactory placode, eye primordia, and the
      trigeminal ganglia. It is also expressed in other organs, such as the pronephros
      and liver primordium. As embryogenesis progresses, it is expressed in the
      migrating melanocytes and lateral line structures. We compare the expression of
      Id4 mRNA with that of Id2 and Id3 and find that the Id genes are expressed in
      complementary patterns during neurogenesis, myogenesis, kidney development, in
      the tailbud, and in the migrating neural crest. To examine the regulation of Id
      gene expression during Xenopus neural development, we show that expression of Id3
      and Id4 can be induced by overexpression of BMP4 in the whole embryo and in
      ectodermal explants. Expression of Id2, Id3, and Id4 in these explants is
      unaffected by the expression of FGF-8 or a dominant-negative Ras (N17ras),
      suggesting that Id genes are not regulated by the FGF signaling pathway in naive
      ectoderm. We also show that Notch signaling can activate Id2 and Id3 expression
      in the whole embryo. In contrast, Id4 expression in the Rohon-Beard cells is
      inhibited by activated Notch and increased by a dominant-negative Delta. This may
      reflect an increase in Rohon-Beard cells in response to inhibition of Notch
      signaling rather than transcriptional regulation of Id4. Finally, to compare the
      activities of Id2, Id3, and Id4, we use animal cap explants and in vivo
      overexpression to show that Id proteins can differentially inhibit the activities
      of neurogenin and neuroD, both neurogenic bHLH molecules and MyoD, a myogenic
      bHLH protein. Id4 is able to inhibit the activity all these bHLH molecules, Id2
      inhibits MyoD and neuroD, while Id3 blocks only neuroD activity in our assays.

PMID- 14651923
TI  - Sonic hedgehog regulates prostatic growth and epithelial differentiation.
AB  - The Sonic hedgehog (SHH)-signalling pathway mediates epithelial-mesenchymal
      interactions in several tissues during development and disease, and we have
      investigated its role in rat ventral prostate (VP) development. We have
      demonstrated that Shh and Ptc expression correlates with growth and development
      of the prostate and that their expression is not regulated by androgens in the
      VP. Prostatic budding was induced in response to testosterone in Shh null mouse
      urogenital sinus (UGS) explants grown in vitro and in rat UGS explants cultured
      with cyclopamine, suggesting that SHH-signalling is not critical for prostatic
      induction. SHH-signalling was disrupted at later stages of VP development (in
      vitro), resulting in a reduction in organ size, an increase in ductal tip number,
      and reduced proliferation of ductal tip epithelia. The addition of recombinant
      SHH to VPs grown in vitro caused a decrease in ductal tip number and expansion of
      the mesenchyme. In the presence of testosterone, inhibition of SHH-signalling
      accelerated the canalisation of prostatic epithelial ducts and resulted in ducts
      that showed morphological similarities to cribiform prostatic intraepithelial
      neoplasia (PIN). The epithelia of these ducts also demonstrated precocious and
      aberrant differentiation, when examined by immunohistochemistry for p63 and
      cytokeratin 14. In conclusion, we show that SHH-signalling is not essential for
      prostatic induction, but is important for prostatic growth, branching, and
      proliferation, and that androgen-stimulated growth in the absence of signalling
      from the SHH pathway results in aberrant epithelial differentiation.

PMID- 14651924
TI  - Roundabout gene family functions during sensory axon guidance in the drosophila
      embryo are mediated by both Slit-dependent and Slit-independent mechanisms.
AB  - roundabout (robo) family genes play key roles in axon guidance in a wide variety
      of animals. We have investigated the roles of the robo family members, robo,
      robo2, and robo3, in the guidance of sensory axons in the Drosophila embryo. In
      robo(-/-), slit(-/-), and robo(-/+) slit(-/+) mutants, lateral cluster sensory
      neurons misproject to cells and axons in the nearby ventral' (v') cluster. These
      phenotypes, together with the normal expression pattern of Slit and Robo, suggest
      that Slit ligand secreted from the epidermis interacts with Robo receptors on
      lateral cluster sensory growth cones to limit their exploration of nearby
      attractive substrates. The most common sensory axon phenotype seen in robo2(-/-)
      mutants was misprojection of dorsal cluster sensory axons away from their normal
      growth substrate, the transverse connective of the trachea. slit appears to play
      no role in this aspect of sensory axon growth. Robo2 is expressed, not on the
      dorsal sensory axons, but on the transverse connective. These results suggest a
      novel, non-cell-autonomous mechanism for axon guidance by robo family genes:
      Robo2 expressed on the trachea acts as an attractant for the dorsal sensory
      growth cones.

PMID- 14651925
TI  - Functional analysis of the domains of the C elegans Ror receptor tyrosine kinase
      CAM-1.
AB  - cam-1 encodes a Caenorhabditis elegans orphan receptor tyrosine kinase (RTK) of
      the Ror family that is required for cell migration and to orient cell polarity.
      Ror RTKs share a common domain structure. The predicted extracellular region
      contains immunoglobulin (Ig), cysteine-rich (CRD), and kringle (Kri) domains.
      Intracellularly are tyrosine kinase (Kin) and serine- and threonine (S/T)-rich
      domains. To investigate the functional requirement for CAM-1 domains in mediating
      cell migration, we engineered deletions that remove various domains and assessed
      the ability of these CAM-1 derivatives to rescue cam-1 mutant phenotypes. We find
      that the Ig, Kri, Kin, and S/T domains are dispensable for cell migration, but
      the CRD is required. Surprisingly, the entire intracellular region of CAM-1 is
      not required for proper cell migration. Most notably, a version of CAM-1 from
      which all domains besides the CRD and transmembrane domains have been deleted is
      able to rescue the migration of a single cell type, although not those of other
      cell types. Our results show that CAM-1 does not function exclusively as a
      canonical RTK and that it may function, at least in part, to regulate the
      distribution of a secreted ligand-possibly a Wnt protein.

PMID- 14651926
TI  - Zic2 is required for neural crest formation and hindbrain patterning during mouse
      development.
AB  - The Zic genes are the vertebrate homologues of the Drosophila pair rule gene odd
      paired. It has been proposed that Zic genes play several roles during neural
      development including mediolateral segmentation of the neural plate, neural crest
      induction, and inhibition of neurogenesis. Initially during mouse neural
      development Zic2 is expressed throughout the neural plate while later on
      expression in the neurectoderm becomes restricted to the lateral region of the
      neural plate. A hypomorphic allele of Zic2 has demonstrated that in the mouse
      Zic2 is required for the timing of neurulation. We have isolated a new allele of
      Zic2 that behaves as a loss of function allele. Analysis of this mutant reveals
      two further functions for Zic2 during early neural development. Mutation of Zic2
      results in a delay of neural crest production and a decrease in the number of
      neural crest cells that are produced. These defects are independent of
      mediolateral segmentation of the neurectoderm and of dorsal neurectoderm
      proliferation, both of which occur normally in the mutant embryos. Additionally
      Zic2 is required during hindbrain patterning for the normal development of
      rhombomeres 3 and 5. This work provides the first genetic evidence that the Zic
      genes are involved in neural crest production and the first demonstration that
      Zic2 functions during hindbrain patterning.

PMID- 14651927
TI  - The zebrafish band 4.1 member Mir is involved in cell movements associated with
      gastrulation.
AB  - Cellular processes rely on dynamic events occurring between the cortical
      cytoskeleton and plasma membrane. Members of the Band 4.1 superfamily, which are
      best known for their ability to tether the cytoskeleton to the plasma membrane,
      play prominent structural and regulatory roles that influence cell-cell and cell
      substrate interactions, endo- and exocytosis, cell polarity, migration,
      proliferation, and differentiation. We have identified a new member of the
      zebrafish Band 4.1 superfamily, which is the homolog of human myosin regulatory
      light chain interacting protein (MIR), and have examined its role in embryonic
      development. Zebrafish Mir contains the conserved amino-terminal plasma membrane
      binding FERM (Band 4.1/ezrin/radixin/moesin) domain as well as other putative
      protein-protein interacting domains, including a RING finger. Overall, zebrafish
      Mir is 71% identical to human MIR located at chromosome 6p23-p22.3, and maps on
      linkage group 19 to a region of synteny with human chromosome 6. In situ
      hybridization and RT-PCR revealed that mir is expressed maternally and
      ubiquitously throughout development. Blocking Mir translation using a mir
      specific, morpholino-based, knock-down strategy or expressing Mir constructs
      lacking the RING finger domain disrupts gastrulation and leads to subsequent
      trunk and tail defects. In severe cases, morphants exogastrulate. The synergistic
      effect seen when two mir-specific morpholinos are used in conjunction reflects
      the specific knock-down of mir. In addition, morphant phenotypes induced by mir
      specific morpholinos are rescued by overexpression of the full-length Mir. In
      situ hybridization analysis with mesodermal- and neural-specific markers shows
      that morphants exhibit a delay in cell movements associated with gastrulation,
      epiboly, convergence, and extension. A yeast two-hybrid analysis was performed to
      identify binding partners that may participate with Mir during gastrulation, and
      Annexin V, a calcium channel protein, was isolated. At early developmental
      stages, annexin V transcripts colocalize with mir, but after gastrulation,
      annexin V mRNA becomes localized to the distal tail region and an area in the
      olfactory placode. At the protein level, Mir colocalizes with Annexin V when
      expressed in COS cells. Together, these results indicate that Mir is essential
      for embryonic development and that its role in early embryonic development likely
      involves calcium-dependent mechanisms essential during the extensive cell
      movements associated with gastrulation.

PMID- 14651928
TI  - Id expression in amphioxus and lamprey highlights the role of gene cooption
      during neural crest evolution.
AB  - Neural crest cells are unique to vertebrates and generate many of the adult
      structures that differentiate them from their closest invertebrate relatives, the
      cephalochordates. Id genes are robust markers of neural crest cells at all stages
      of development. We compared Id gene expression in amphioxus and lamprey to ask if
      cephalochordates deploy Id genes at the neural plate border and dorsal neural
      tube in a manner similar to vertebrates. Furthermore, we examined whether Id
      expression in these cells is a basal vertebrate trait or a derived feature of
      gnathostomes. We found that while expression of Id genes in the mesoderm and
      endoderm is conserved between amphioxus and vertebrates, expression in the
      lateral neural plate border and dorsal neural tube is a vertebrate novelty.
      Furthermore, expression of lamprey Id implies that recruitment of Id genes to
      these cells occurred very early in the vertebrate lineage. Based on expression in
      amphioxus we postulate that Id cooption conferred sensory cell progenitor-like
      properties upon the lateral neurectoderm, and pharyngeal mesoderm-like properties
      upon cranial neural crest. Amphioxus Id expression is also consistent with
      homology between the anterior neurectoderm of amphioxus and the presumptive
      placodal ectoderm of vertebrates. These observations support the idea that neural
      crest evolution was driven in large part by cooption of multipurpose
      transcriptional regulators from other tissues and cell types.

PMID- 14651929
TI  - Temporal and spatial regulation of VEGF-A controls vascular patterning in the
      embryonic lung.
AB  - Vascular endothelial growth factor-A (VEGF-A) is required for vascular
      development throughout the embryo and has been proposed to play an important role
      in pulmonary vascular patterning. Expressed by the embryonic respiratory
      epithelium, VEGF-A signals endothelial cells within the splanchnic mesenchyme. To
      refine understanding of the spatial and temporal role of VEGF-A in lung
      morphogenesis, isoform VEGF164 was expressed under conditional control in distal
      and proximal airway epithelial cells. Unexpectedly, increased expression of
      VEGF164 in distal lung disrupted peripheral vascular net assembly and arrested
      branching of airways tubules without altering endothelial cell proliferation or
      apoptosis. Peripheral airway branching and vascular smooth muscle patterning were
      also altered. In contrast, expression of VEGF164 by epithelial cells of the
      conducting airways caused atypical evaginations of small capillary-like vessels
      into large airways but did not alter peripheral vascular net assembly or
      branching morphogenesis. These data demonstrate that the differential response of
      endothelial cells in distal vascular beds and large central blood vessels is
      established early in lung development. Precise temporal and spatial expression of
      VEGF-A is required for vascular patterning during lung morphogenesis. Disruption
      of pulmonary vascular assembly perturbs reciprocal interactions with epithelium
      leading to altered airway branching morphogenesis.

PMID- 14651930
TI  - Interplay between FGF, one-eyed pinhead, and T-box transcription factors during
      zebrafish posterior development.
AB  - The zebrafish T-box transcription factors spadetail (spt) and the brachyury
      ortholog no tail (ntl) are together essential for posterior mesoderm formation.
      In addition to being functionally redundant, spt and ntl also genetically
      interact with zygotic mutant alleles of one-eyed pinhead (Zoep), leading to
      synergistic mesodermal defects. Here we have used genetic and pharmacological
      assays to address the mechanism of these interactions. We show that Zoep and ntl
      are together required upstream of spt expression, accounting for the severity of
      the mesodermal defects in Zoep;ntl embryos. Since Xenopus brachyury is proposed
      to regulate fgf expression, and FGF signaling is required for spt expression, we
      analyzed the involvement of the FGF signaling pathway in these genetic
      interactions. Using a specific inhibitor of FGFR activity to indirectly assay the
      strength of FGF signaling in individual embryos, we found that spt and ntl mutant
      embryos were both hypersensitive to the FGFR inhibitor. This hypersensitivity is
      consistent with the possibility that Spt and Ntl function upstream of FGF
      signaling. Furthermore, we show that minor pharmacological or genetic
      perturbations in FGF signaling are sufficient to dramatically enhance the Zoep
      mutant phenotype, providing a plausible explanation for why Zoep genetically
      interacts with spt and ntl. Finally, we show that Zoep and ace/fgf8 function are
      essential for the formation of all posterior tissues, including spinal cord.
      Taken together, our data provide strong in vivo support for the regulation of FGF
      signaling by T-box transcription factors, and the cooperative activity of Oep and
      FGF signaling during the formation of posterior structures.

PMID- 14651931
TI  - Gustatory neurons derived from epibranchial placodes are attracted to, and
      trophically supported by, taste bud-bearing endoderm in vitro.
AB  - Taste buds are multicellular receptor organs innervated by the VIIth, IXth, and
      Xth cranial nerves. In most vertebrates, taste buds differentiate after nerve
      fibers have reached the lingual epithelium, suggesting that nerves induce taste
      buds. However, under experimental conditions, taste buds of amphibians develop
      independently of innervation. Thus, rather than being induced by nerves, the
      developing taste periphery likely regulates ingrowing nerve fibers. To test this
      idea, we devised a culture approach using axolotl embryos. Gustatory neurons were
      generated from cultured epibranchial placodes, and when cultured alone, axon
      outgrowth was random over 4 days, a time period coincident with axon growth to
      the periphery in vivo. In contrast, cocultures of placodal neurons with
      oropharyngeal endoderm (OPE), the normal taste bud-containing target for these
      neurons, resulted in neurite growth toward the target tissue. Unexpectedly,
      placodal neurons also grew toward flank ectoderm (FE), which these neurons do not
      encounter in vivo. To compare further the impact of OPE and FE explants on
      gustatory neurons, cocultures were extended and examined at 6, 8, and 10 days,
      when, in vivo, placodal fibers have innervated the epithelium but prior to taste
      bud formation, when taste buds have differentiated and are innervated, and when
      the mouth has opened and larvae have begun to feed, respectively. The behavior of
      placodal axons with respect to target type did not differ between OPE and FE
      cocultures at 6 days. However, by 8 days, differences in axonal outgrowth were
      observed with respect to target type, and these differences were enhanced by 10
      days in vitro. Most clearly, exuberant placodal fibers grew in 10-day OPE
      cocultures, and numerous neurites had invaded OPE explants by this time, whereas
      gustatory neurites were sparse in FE cocultures, and rarely approached and almost
      never contacted FE explants. Thus, embryonic endoderm destined to give rise to
      taste buds specifically attracts its innervation early in development, as
      placodal neurons send out axons. Later, when gustatory axons synapse with
      differentiated taste buds in vivo, the OPE provides trophic support for cultured
      gustatory neurons.

PMID- 14651932
TI  - Bonsai, a ribosomal protein S15 homolog, involved in gut mitochondrial activity
      and systemic growth.
AB  - The regulation of cellular growth is crucial in the control of cell
      proliferation. While most of the metabolic energy necessary to sustain growth is
      produced in mitochondria, the regulation of mitochondrial activity and its
      implications for growth have remained unexplored. Here, a gene named bonsai is
      described, which is essential for normal growth in Drosophila. The Bonsai protein
      bears strong homology to prokaryotic ribosomal protein S15 and localizes to
      mitochondria, suggesting a role in mitochondrial protein translation.
      Accordingly, bonsai mutants have defective mitochondrial activity, but
      surprisingly, only the gut appears affected. Consistent with these observations,
      bonsai is predominantly expressed in the gut. These results show that bonsai
      plays a preponderant role in gut mitochondria. Although gut mitochondrial
      respiration is altered in bonsai mutants, the digestive process appears normal,
      suggesting that a gut function other than digestion is impaired in the mutants.
      Cytochrome c oxidase, a respiratory chain enzyme partly encoded by the
      mitochondrial genome, is found to be active in bonsai mutants. This suggests that
      mitochondrial translation is not abolished in the mutants. Altogether, these
      observations suggest that mitochondrial activity is regulated at the tissue
      specific level and that this regulation has profound implications for growth and
      development.

PMID- 14651933
TI  - STK, the src homologue, is responsible for the initial commitment to develop head
      structures in Hydra.
AB  - STK, the Src tyrosine kinase homologous of the fresh water polyp hydra, is a key
      component of the signal transduction system for cell differentiation in this
      organism. Its activity is strongly increased 6 h after decapitation, and the
      inhibition of its activity with PP2/AG1879 prevents head development. We
      generated STK(-) polyps by using double-stranded RNA interference; STK activity
      of those polyps is blocked through time. STK RNAi silenced animals could not
      regenerate the head, but the foot, and could not reproduce asexually. The
      silencing of STK causes the development of ectopic heads in decapitated polyps in
      the first third of their body. Some head-specific genes, like Ks1, HyTcf, and
      Hybra1, seem to be regulated by the signaling pathway mediated by STK because
      their expression is modified in the STK(-) polyps. These findings support an
      important function for STK in the initial commitment of cells to develop head
      structures in hydra.

PMID- 14651934
TI  - A cell-adhesion pathway regulates intercellular communication during
      Dictyostelium development.
AB  - Cell adhesion molecules play an important physical role in shaping the structure
      of multicellular organisms. Recent studies show that they also play a role in
      intracellular and intercellular signaling. We describe a cell adhesion pathway
      that is mediated by the intercellular communication genes comC, lagC, and lagD
      during Dictyostelium development. Disruptions of these genes result in strains
      that are unable to generate spores when developed in a pure population but are
      capable of sporulation when developed in chimerae with wild-type cells. In
      contrast, any pair-wise chimera of the three mutants fails to form spores. We
      postulate that the wild-type cells supply the mutant cells with a signal that
      partially rescues their sporulation. We also propose that the three mutants are
      deficient in the production of that signal, suggesting that the three genes
      function in one signaling pathway. In support of that notion, the mutant cells
      share common non-cell-autonomous prespore and prestalk-specific defects and a
      common pattern of developmental progression and regression. We provide
      transcriptional and functional evidence for a network in which comC inhibits lagC
      and activates lagD expression, lagC and lagD are mutually inductive, and the cell
      adhesion gene lagC is the terminal node in this signaling network.

PMID- 14651935
TI  - Fgf signalling is required for formation of cartilage in the head.
AB  - Characterisation of human craniofacial syndromes and studies in transgenic mice
      have demonstrated the requirement for Fgf signalling during morphogenesis of
      membrane bone of the cranium. Here, we report that Fgf activity is also required
      for development of the oro-pharyngeal skeleton, which develops first as cartilage
      with some elements subsequently becoming ossified. We show that inhibition of FGF
      receptor activity in the zebrafish embryo following neural crest emigration from
      the neural tube results in complete absence of neurocranial and pharyngeal
      cartilages. Moreover, this Fgf signal is required during a 6-h period soon after
      initiation of neural crest migration. The spatial and temporal expression of Fgf3
      and Fgf8 in pharyngeal endoderm and ventral forebrain and its correlation with
      patterns of Fgf signalling activity in migrating neural crest makes them
      candidate regulators of cartilage development. Inhibition of Fgf3 results in the
      complete absence of cartilage elements that normally form in the third, fourth,
      fifth, and sixth pharyngeal arches, while those of the first, second, and seventh
      arches are largely unaffected. Inhibition of Fgf8 alone has variable, but mild,
      effects. However, inhibition of both Fgf3 and Fgf8 together causes a complete
      absence of pharyngeal cartilages and the near-complete loss of the neurocranial
      cartilage. These data implicate Fgf3 and Fgf8 as key regulators of cartilage
      formation in the vertebrate head.

PMID- 14651936
TI  - Anterior neural plate regionalization in cripto null mutant mouse embryos in the
      absence of node and primitive streak.
AB  - The relation between the role of the organizer at the gastrula stage and the
      activity of earlier signals in the specification, maintenance, and
      regionalization of the developing brain anlage is still controversial. Mouse
      embryos homozygous for null mutation in the cripto gene die at about 9.0 days
      postcoitum (d.p.c.) and fail to gastrulate and to form the node (the primary
      organizer). Here, we study the presence and the distribution of anterior neural
      plate molecular domains in cripto null mutants. We demonstrate that, in cripto(-/
      ) embryos, the main prosencephalic and mesencephalic regions are present and that
      they assume the correct topological organization. The identity of the anterior
      neural domains is maintained in mutant embryos at 8.5 d.p.c., as well as in
      mutant explants dissected at 8.5 d.p.c. and cultured in vitro for 24 h. Our data
      imply the existence of a stable neural regionalization of anterior character
      inside the cripto(-/-) embryos, despite the failure in both the gastrulation
      process and node formation. These results suggest that, in mouse embryos, the
      specification of the anterior neural identities can be maintained without an
      absolute requirement for the embryonic mesoderm and the node.

PMID- 14651937
TI  - Ephrin-A2 regulates position-specific cell affinity and is involved in cartilage
      morphogenesis in the chick limb bud.
AB  - In the developing limb bud, mesenchymal cells show position-specific affinity,
      suggesting that the positional identity of the cells is represented as their
      surface properties. Since the affinity is regulated by
      glycosylphosphatidylinositol (GPI)-anchored cell surface proteins, and by EphA4
      receptor tyrosine kinase, we hypothesized that the GPI-anchored ligand, the
      ephrin-A family, also contributes to the affinity. Here, we describe the role of
      ephrin-A2 in the chick limb bud. Ephrin-A2 protein is uniformly distributed in
      the limb bud during early limb development. As the limb bud grows, expression of
      ephrin-A2 is strong in its proximal-to-intermediate regions, but weak distally.
      The position-dependent expression is maintained in vitro, and is regulated by FGF
      protein, which is produced in the apical ectodermal ridge. To investigate the
      role of ephrin-A2 in affinity and in cartilage morphogenesis of limb mesenchyme,
      we ectopically expressed ephrin-A2 in the limb bud using the retrovirus vector,
      RCAS. Overexpressed ephrin-A2 modulated the affinity of the mesenchymal cells
      that differentiate into autopod elements. It also caused malformation of the
      autopod skeleton and interfered with cartilage nodule formation in vitro without
      inhibiting chondrogenesis. These results suggest that ephrin-A2 regulates the
      position-specific affinity of limb mesenchyme and is involved in cartilage
      pattern formation in the limb.

PMID- 14651938
TI  - Xenopus Xlmo4 is a GATA cofactor during ventral mesoderm formation and regulates
      Ldb1 availability at the dorsal mesoderm and the neural plate.
AB  - We have identified and functionally characterized the Xenopus Xlmo4 gene, which
      encodes a member of the LIM-domain-only protein family. Xlmo4 is activated at
      gastrula stages in the mesodermal marginal zone probably in response to BMP4
      signaling. Soon after, Xlmo4 is downregulated in the dorsal region of the
      mesoderm. This repression seems to be mediated by organizer-expressed repressors,
      such as Gsc. Xlmo4 downregulation is necessary for the proper formation of this
      territory. Increasing Xlmo4 function in this region downregulates Spemman
      Organizer genes and suppresses dorsal-anterior structures. By binding to Ldb1,
      Xlmo4 may restrict the availability of this cofactor for transcription factors
      expressed at the Spemman Organizer. In the ventral mesoderm, Xlmo4 is required to
      establish the identity of this territory by acting as a positive cofactor of GATA
      factors. In the neural ectoderm, Xlmo4 expression depends on Xiro homeoprotein
      activity. In this region, Xlmo4 suppresses differentiation of primary neurons and
      interferes with gene expression at the Isthmic Organizer, most likely by
      displacing Ldb1 from active transcription factor complexes required for these
      processes. Together, our data suggest that Xlmo4 uses distinct mechanisms to
      participate in different processes during development.

PMID- 14651939
TI  - Drosophila hemolectin gene is expressed in embryonic and larval hemocytes and its
      knock down causes bleeding defects.
AB  - We have previously identified and characterized Drosophila hemolectin (Hml) in
      the conditioned medium of a Drosophila cell line. The deduced amino acids
      sequence contains a number of domains conserved in human von Willebrand factor,
      coagulation factor V/VIII, and complement factors. To characterize Hml
      localization and function, we have established two transgenic lines (hml-GAL4 and
      UAS-hmlRNAi). By crossing hml-GAL4 with UAS-eGFP, we observed that Hml is
      specifically expressed in embryonic and in larval hemocytes. We determined that
      Hml is expressed in a subpopulation of plasmatocytes and crystal cells but not in
      lamellocytes. hml RNAi larvae are viable and do not display obvious developmental
      defects under normal conditions. However, they show a bleeding defect upon
      injury. We confirmed that the failure to seal a wound is not due to a defect in
      melanin production or in phenoloxidase activity. The expression of antimicrobial
      peptides was not significantly affected on hml RNAi adults. Altogether, our data
      strongly suggest that Hml is involved in hemostasis and/or coagulation in
      Drosophila larvae.

PMID- 14651940
TI  - Innate immunity at the forefront of psychoneuroimmunology.
AB  - The last 15 years of research in psychoneuroimmunology have been marked by a
      renewed interest in the mechanisms of inflammation and participation of the brain
      in these mechanisms. Peripheral proinflammatory cytokines produced by activated
      accessory immune cells act in the brain to trigger sickness, in the form of
      fever, pituitary-adrenal axis activation, and sickness behavior. Communication
      between the periphery and brain takes place via both neural and humoral pathways.
      Recognition of the role of local production of cytokines and their downstream
      messengers in the central nervous system opens important new vistas for
      understanding and treating non-specific neurovegetative and psychiatric symptoms
      of diseases. In this presidential address, I present the main methodological and
      conceptual developments that have allowed such progress.

PMID- 14651941
TI  - Molecular regulation of CD40 gene expression in macrophages and microglia.
AB  - Inflammatory events in the central nervous system (CNS) contribute to the disease
      process in a variety of neuroinflammatory diseases such as multiple sclerosis
      (MS), Alzheimer's Disease (AD), and cerebral ischemia, and activated
      macrophages/microglia are central to this response. Immunological activation of
      these cells leads to the production of a wide array of cytokines, chemokines,
      matrix metalloproteinases and neurotoxins, and ultimately to glial/neuronal
      injury and death. The CD40 molecule has an important role in promoting
      inflammatory responses by macrophages/microglia, since interaction with its
      cognate ligand, CD154, leads to secretion of cytokines and neurotoxins. Aberrant
      CD40 expression by macrophages/microglia, induced by cytokines such as IFN-gamma
      and TNF-alpha, contributes to neuroimmunologic cascades in the CNS. Strategies to
      suppress CD40 expression may attenuate inflammation and neuronal damage within
      the CNS, which will ultimately be of benefit in neuroinflammatory diseases. The
      mediators that regulate expression of CD40 in macrophages/microglia (both
      induction and inhibition) function at the level of gene transcription. In this
      review, we present an overview of the molecular basis of CD40 expression in
      macrophages/microglia. The signal transduction pathways and transcription factors
      employed by IFN-gamma and TNF-alpha to induce CD40 expression are described, as
      are the cis-elements in the CD40 promoter that are critical for CD40
      transcription. Information is provided on the mechanism(s) underlying suppression
      of CD40 in macrophages/microglia by immunomodulatory agents such as IL-4, TGF
      beta, neuropeptides, neurotrophins, and statins. A comprehensive assessment of
      CD40 production and function in macrophages/microglia will establish the
      foundation for future therapeutic manipulation of this critical immunoregulatory
      protein.

PMID- 14651942
TI  - Maternal vaccination: is it effective in the face of stress?

PMID- 14651943
TI  - Prenatal transfer of low amounts of herpes simplex virus (HSV)-specific antibody
      protects newborn mice against HSV infection during acute maternal stress.
AB  - Given their immunocompromised status, neonates rely heavily upon maternally
      derived, herpes simplex virus (HSV)-specific antibody for resistance to HSV
      infection. Interestingly, previous studies have documented a decreased transfer
      of maternal IgG antibody and immunocompetence of the offspring following
      perinatal exposure to stress-induced corticosterone. However, we recently
      demonstrated that the transplacental transfer of relatively high amounts of HSV
      specific antibody is resilient to acute maternal stress and protects neonatal
      mice against HSV-2-associated mortality. Our current studies demonstrate that
      transplacentally acquired, HSV-specific antibody declines rapidly in neonate
      serum such that by day 7 postnatal only 10% of this antibody remains. Prenatal
      stress does not affect the overall kinetics with which the HSV-specific antibody
      declines. Surprisingly, this relatively low level of antibody is still sufficient
      to protect 7-day-old mice against HSV-associated mortality. To extend these
      studies, we utilized an immunization strategy that elicits low levels of HSV
      specific antibody in maternal serum. We demonstrated that despite a stress
      induced increase in corticosterone, the prenatal transfer and protective capacity
      of low amounts of HSV-specific antibody remains intact during acute maternal
      stress.

PMID- 14651944
TI  - 5-HT1A-mediated promotion of mitogen-activated T and B cell survival and
      proliferation is associated with increased translocation of NF-kappaB to the
      nucleus.
AB  - Mitogenic activation of T and B lymphocytes induces expression of the 5-HT(1A)
      receptor through an NF-kappaB-dependent signaling pathway. In the present study,
      it is shown that serotonin (5-HT), as well as the selective 5-HT(1A) receptor
      agonist R-DPAT, increase cell survival and S phase transition in mouse
      splenocytes stimulated by T or B cell mitogens. Further examination of the
      mechanisms underlying increased cell survival revealed that 5-HT and R-DPAT
      inhibited apoptotic cell death, assessed both by soluble DNA content,
      internucleosomal DNA cleavage, and hypodiploid DNA content. Additionally, 5-HT
      and R-DPAT treatment increased intranuclear levels of the p50 and p65 subunits of
      NF-kappaB. Potentiation by 5-HT and R-DPAT of mitogen-activated cell survival, S
      phase transition, and nuclear localization of NF-kappaB, as well as inhibition of
      apoptosis, were all reversed by the selective 5-HT(1A) receptor antagonist WAY
      100635. These results indicate that 5-HT(1A)-mediated promotion of cell survival
      and proliferation of mitogen-activated T and B lymphocytes is associated with
      increased translocation of NF-kappaB in the nucleus.

PMID- 14651945
TI  - Consequences of repeated early isolation in domestic piglets (Sus scrofa) on
      their behavioural, neuroendocrine, and immunological responses.
AB  - Stress in the form of intermittent maternal deprivation and social isolation
      during early postnatal life in rats and monkeys produces persistent changes in
      physiology and behaviour. In farm animals physiological consequences of
      disrupting mother-infant interactions with respect to health and animal welfare
      are relatively unknown. Therefore, the aim of the present study was to
      investigate the behavioural, neuroendocrine and immunological consequences of a 2
      h daily social isolation from day 3 to day 11 of age in domestic piglets as well
      as potential long-term effects on the brain-endocrine-immune regulation. Repeated
      social isolation resulted in significantly decreased open-field activity
      (locomotion, vocalization) during the isolation period, increased basal cortisol
      concentrations and decreased lymphocyte proliferation in response to concanavalin
      A and pokeweed mitogen one day after the isolation. There was also a significant
      increase of interleukin-1beta (IL-1beta) concentration in hippocampus in isolated
      piglets compared to controls at this time. Six weeks after isolation significant
      enhanced basal ACTH concentrations as well as higher IL-1beta content and
      glucocorticoid receptor (GR) binding in hippocampus were found. These endocrine
      and immune responses were associated with decreased CRH levels in the
      hypothalamus and increased CRH content in the amygdala. The present data indicate
      that early social isolation in pigs may cause changes in behavioural,
      neuroendocrine, and immune regulation and produce long-term effects not only on
      the activity of the hypothalamic-pituitary-adrenal (HPA) system, but also on the
      immune-brain circuitry with possible negative consequences in health and welfare
      of commercial pigs. Using the pig as a suitable animal model, the finding of this
      study may also have some implications for the etiology of anxiety and depression
      in humans.

PMID- 14651946
TI  - Effects of bacterial superantigens on behavior of mice in the elevated plus maze
      and light-dark box.
AB  - Bacterial superantigens, such as staphylococcal enteroxins A and B (SEA/SEB)
      stimulate T cells to produce high levels of cytokines in blood. Previously it had
      been shown that these toxins were capable of stimulating increased neuroendocrine
      activity and enhanced behavioral reactivity to novel gustatory and non-gustatory
      stimuli. Therefore, it was suggested that these superantigens may promote anxiety
      like behavior. In the current set of experiments, BALB/cByJ and C57BL/6J male
      mice were challenged with either SEB (50 microg) or SEA (5 or 10 microg) and
      tested for behavior in the elevated plus maze (EPM). Results suggested an absence
      of increased anxiety-like behavior, with exploration of the open arms being
      enhanced by SEA or SEB treatment. In another test of anxiety, the light-dark box,
      SEB challenge of BALB/cByJ mice 90 min prior to testing, did not alter exit
      latency, activity nor time spent in the dark. However, in a second experiment, it
      was found that if animals were first tested for consumption, followed by testing
      in the light-dark box, SEB challenged animals displayed increased exit latency
      and reduced exploration. These studies suggest that in standard tests of rodent
      anxiety-like behavior, evidence for the induction of anxiety-like processes
      subsequent to challenge with SEA or SEB is not patently discernable. However,
      neurobiological events induced by immunological challenge might synergize with
      reactivity to psychogenic and/or gustatory stimuli, thereby resulting in
      increased anxiety-like behavior that could be unmasked by standard behavioral
      tests such as the light-dark box or EPM.

PMID- 14651947
TI  - Effects of acute stress, relaxation, and a neurogenic inflammatory stimulus on
      interleukin-6 in humans.
AB  - Effects of three experimental manipulations: mental stress, relaxation, and a
      nociceptive inflammatory stimulus, capsaicin, on levels of interleukin-6 (IL-6)
      were examined. Fifty subjects were pre-trained in relaxation and then randomized
      to a stress (Stroop test), relaxation (tape), or control (video) manipulation.
      Subjects participated in an evening reactivity session including 20 min of
      stress, relaxation, or control followed by a capsaicin injection in the forearm.
      Cardiovascular variables and levels of IL-6 were measured before and after the
      manipulation, and at regular intervals up to 60 min post-capsaicin. Group
      assignment did not differentially affect change in IL-6 over time, either before
      or after capsaicin. Small but significant increases in IL-6 were seen at 60 min
      post-capsaicin. These findings suggest that an acute stress manipulation does not
      modulate IL-6 within this time frame. Although IL-6 did increase following a
      neurogenic inflammatory stimulus, it did so subsequent to the maximum flare,
      suggesting that flare mechanisms are independent of IL-6.

PMID- 14651948
TI  - The relationship between distress and the development of a primary immune
      response to a novel antigen.
AB  - Forty-five medical students were recruited to examine the effects of distress on
      the development of an immune response to the novel antigen, keyhole limpet
      hemocyanin (KLH). The subjects' level of distress was manipulated by immunizing
      them either at the time of an important viva voce examination (n=22) or during
      examination-free term time (n=23). This manipulation increased variance amongst
      the subjects, but the emphasis in this research was on individual distress as a
      predictor of immune function. In the group as a whole, the likelihood of
      developing DTH skin responses to KLH was reduced in the more distressed subjects
      (r=-.45; p=.002), independently of a number of behavioral (e.g., sleep
      disturbance) and demographic (e.g., sex) variables. Proliferation of T cells
      against KLH in vitro and the development of anti-KLH IgG antibodies were not
      related to levels of distress. Thus, cellular, rather than humoral, immune
      responses in vivo appear susceptible to the influence of distress. This
      immunization model provides the opportunity to further dissect the basis of these
      stress-immune pathways.

PMID- 14651949
TI  - Enhancement of antibody response by one-trial conditioning: contrasting results
      using different antigens.
AB  - New research in conditioned enhancement of antibody response requires a general
      paradigm effective with different antigens. In this experiment series we applied
      a one-trial protocol using keyhole limpet hemocyanin immunization as an
      unconditioned stimulus. Several different conditions were tested. Two different
      times between conditioning and test trial, two relevant antigen doses and the use
      of an antigen booster during test trial were investigated. We did not find a
      conditioned effect in any of the conditions used. In contrast, we found a
      reliable albeit modest conditioned effect using hen egg lysozyme as unconditioned
      stimulus. By comparing these and other findings we conclude that the number of
      conditioning trials is a possible requirement for a more reliable conditioning of
      antibody response.

PMID- 14651950
TI  - Impaired T-cell dependent humoral response and its relationship with T lymphocyte
      sensitivity to stress hormones in a chronic mild stress model of depression.
AB  - The humoral response and the role of catecholamines and corticosterone were
      analyzed in a chronic mild stress (CMS) model of depression. Mice subjected for
      more than 6 weeks to CMS showed a significant decrease in T-cell dependent
      antibody production. However, T-cell independent humoral response was not
      altered. Serum corticosterone levels and splenic norepinephrine (NE) contents
      showed an early increase but they were not altered after prolonged CMS exposure.
      Nevertheless, hormonal inhibitory effect on T lymphocyte reactivity was higher in
      6-week CMS mice compared to non-exposed animals. Thus, our results suggest that
      the impaired T-cell dependent humoral response in a CMS model of depression is
      neither related to changes in glucocorticoids nor in NE levels but is correlated
      with an increment of T-cell sensitivity to stress hormones. These findings would
      underlie the involvement of catecholamines and glucocorticoid lymphocyte
      receptors in the immune alterations observed in stress and depression.

PMID- 14651951
TI  - Evaluation of the neurorestorative effects of the murine beta-nerve growth factor
      infusions in old rat with cognitive deficit.
AB  - The nerve growth factor (NGF) is known to participate in the regulation of the
      expression levels and activity of the choline acetyltransferase (ChAT) in the
      nervous system. This enzyme is sensitive to the degenerative changes found in
      Alzheimer's disease (AD). We compared the effectiveness of intraparenchymal (ip)
      and intracerebroventricular (icv) administration of the murine beta-NGF (beta
      NGFm) produced in our laboratories, through the determination of the expression
      levels and activity of the ChAT, and the evaluation of behavioral recovery in
      aged rat with cognitive deficit. Our results indicated that icv infusion of beta
      NGFm stimulates the expression levels of ChAT gene in the striatum of old rats.
      Remarkable losses in the ChAT activity were observed in the septum and striatum
      of old rats. Exogenous administration of beta-NGFm produced a significant
      increase of ChAT activity in these brain regions differentially according to the
      administration pathway. The behavioral studies demonstrated that the
      administration pathway is an important factor in order to obtain the best results
      for a neurorestorative treatment.

PMID- 14651952
TI  - Cu/Zn superoxide dismutase can form pore-like structures.
AB  - Mutations in Cu/Zn superoxide dismutase (SOD) are associated with familial
      amyotrophic lateral sclerosis (FALS), a neurodegenerative disease that is
      characterized by the selective death of motor neurons. Despite the genetic
      association made between the protein and the disease, the mechanism by which the
      mutant SOD proteins become toxic is still a mystery. Using wild-type SOD and
      three pathogenic mutants (A4V, G37R, and G85R), we show that the copper-induced
      oxidation of metal-depleted SOD causes its in vitro aggregation into pore-like
      structures, as determined by atomic force microscopy. Because toxic pores have
      been recently implicated in the pathogenic mechanism of other neurodegenerative
      diseases, these results raise the possibility that the aberrant self-assembly of
      oxidatively damaged SOD mutants into toxic oligomers or pores may have a
      pathological role in FALS.

PMID- 14651953
TI  - Bisphenol A induces apoptosis in central neural cells during early development of
      Xenopus laevis.
AB  - Bisphenol A (BPA), known to be a xenoestrogen, is widely used in industry and
      dentistry. In the present study, we investigated the effects of BPA on the early
      development of Xenopus laevis embryos. Stage 6 embryos were exposed to 10-100
      microM BPA. Developmental abnormalities were observed when the embryos were
      exposed to at least 20 microM BPA, with marked developmental abnormalities, such
      as crooked vertebrae and developmental defects of the head and abdomen, detected
      in all embryos up to stage 40. Interestingly, apoptosis occurred specifically in
      central nervous tissue cells of the brain and spinal cord, as assessed by
      histological analysis. BPA-induced malformations and apoptosis were not observed
      in embryos exposed to BPA after stage 10. When embryos were exposed to 10 microM
      17beta-estradiol (E2), abnormalities were also observed until stage 40. However,
      the abnormalities induced by BPA and E2 were different and E2 exposure did not
      induce apoptosis in the central nervous system. Our results indicated that the
      developmental abnormalities and apoptosis induced by BPA exposure were not
      inhibited by the addition of E2. In conclusion, we demonstrated that BPA induced
      marked malformations and specific apoptosis of central nervous system cells
      during early development of X. laevis embryos, and that these BPA effects
      appeared to be due to non-estrogenic activities on developmental processes.

PMID- 14651954
TI  - Adenosine stimulates CREB activation in macrophages via a p38 MAPK-mediated
      mechanism.
AB  - Adenosine is an endogenously released autocoid that has potent receptor-mediated
      modulatory effects on macrophage function. The intracellular pathways mediating
      these effects are incompletely understood. Since adenosine receptor occupancy has
      been associated with activation of the cAMP-PKA system as well as of p38 MAPK and
      p42/44 MAPK, all of which can activate the CREB transcription factor system, we
      hypothesized that adenosine would activate CREB in macrophages. Using RAW 264.7
      macrophages, we found that extracellular adenosine enhanced CREB transcriptional
      activity and increased phosphorylation of nuclear CREB. On the other hand,
      adenosine failed to alter CREB DNA binding. Adenosine stimulated both p38 and
      p42/44 MAPK activation. The p38 MAPK pathway inhibitor SB203580 but not the
      p42/44 MAPK pathway blocker PD98059 decreased adenosine-induced CREB activation,
      indicating that p38 MAPK but not p42/44 MAPK is an upstream mediator of CREB
      activation. Thus, some of the immunomodulatory effects of adenosine in
      macrophages may be explained by its augmenting effect on CREB activation.

PMID- 14651955
TI  - Expression of the Arp11 gene suppresses the tumorigenicity of PC-14 human lung
      adenocarcinoma cells.
AB  - We recently reported the isolation of a novel actin-related gene, Arp11, from a
      PC-14 human lung adenocarcinoma clone with low metastatic and tumorigenic
      ability. In this paper, we report the effect of Arp11 expression on PC-14 tumor
      growth. We transfected a highly metastatic and tumorigenic PC-14 line, Lu-2, with
      an Arp11 expression vector, and obtained five stable transfectants that each
      express Arp11 at different levels. The tumor growth rate of these transformants
      in nude mice and their colony formation in soft agar were reduced in proportion
      to their levels of Arp11 expression. Thus, overexpression of Arp11 may suppress
      tumorigenicity in nude mice. The morphology of the transfectants expressing high
      levels of Arp11 differed clearly from that of Lu-2 and the mock-transfectants as
      the Arp11-transfectants were flat and fibrous, while Lu-2 and the mock
      transfectants were round and were released into the culture medium. An increase
      in the number of actin stress fibers was observed in the Arp11-transfectants 1-12
      3-x and 2-9-2 but not in the mock-transfected lines. Our results suggest that the
      overexpression of Arp11 regulates the transcription of multiple genes that are
      involved in suppressing tumorigenicity.

PMID- 14651956
TI  - Identification of GM-CSF in Paneth cells using single-cell RT-PCR.
AB  - Paneth cells, granule-containing cells located at the bottom of the intestinal
      crypts, have a role in innate mucosal immunity. We identified the exclusive
      expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in Paneth
      cells using single-cell reverse transcription-polymerase chain reaction and cDNA
      array. Cytosolic total RNA was aspirated from single Paneth cells and other
      villous epithelial cells (non-Paneth cells) of rats using capillary
      micropipettes. In addition to lysozyme, secretory phospholipase A2, defensin, TNF
      alpha, and xanthine dehydrogenase genes, cDNA array analysis revealed that the GM
      CSF gene is specifically present in Paneth cells, whereas GM-CSF receptor beta
      chain mRNA is expressed in Paneth cells and other epithelial cells. There was
      intense immunohistochemical staining of GM-CSF in Paneth cells but not in other
      epithelial cells. Treatment of IEC6 cells with GM-CSF enhanced expression of CD80
      and CD86. Thus, GM-CSF in Paneth cells might have an important role in mucosal
      immunity through increasing the expression of costimulatory molecules in
      epithelial cells.

PMID- 14651957
TI  - Sphingosine-1-phosphate markedly induces matrix metalloproteinase and integrin
      dependent human endothelial cell invasion and lumen formation in three
      dimensional collagen and fibrin matrices.
AB  - Endothelial cell invasion is a key step in angiogenic blood vessel formation.
      Sphingosine-1-phosphate (S1P) has been previously reported to play a role in
      endothelial cell proliferation, survival, migration, and angiogenesis. Here, we
      examine the ability of S1P to regulate human endothelial cell invasion into three
      dimensional collagen or fibrin matrices. We show that S1P potently stimulated
      human endothelial cell invasion, lumen formation, and branching morphogenesis in
      collagen, and fibrin matrices, (5- and 15-fold increases in invasion were
      observed, respectively). The S1P-induced invasion response was pertussis-toxin
      sensitive and completely dependent on integrins. Addition of integrin blocking
      reagents revealed that the alpha2beta1 integrin regulated invasion in collagen
      matrices, while a combination of alphavbeta3 and alpha5beta1 integrins regulated
      invasion in fibrin. Additionally, the S1P-induced invasion response was dependent
      on matrix metalloproteinases (MMPs). Tissue inhibitor of metalloproteinase-3
      (TIMP-3) was the only physiologic inhibitor of metalloproteinases that completely
      inhibited the potent stimulation of invasion induced by S1P. In contrast, TIMP-1
      had no blocking effect on invasion or morphogenesis, while TIMP-2 and TIMP-4
      partially reduced invasion but completely blocked lumen formation events.
      Collectively, these data reveal a marked ability of S1P to induce
      metalloproteinase- and integrin-dependent human endothelial cell invasion and
      morphogenesis in both collagen and fibrin three-dimensional matrices, the two
      most physiologically relevant matrices for angiogenesis.

PMID- 14651959
TI  - Divergent roles of GSK3 and CDK5 in APP processing.
AB  - Glycogen synthase kinase-3 (GSK3) and cyclin-dependent kinase 5 (CDK5) are
      related serine/threonine kinases that have been well studied for their role in
      tau hyperphosphorylation, however, little is known about their significance in
      APP processing. Here we report that GSK3 and CDK5 are involved in APP processing
      in a divergent manner. Specific inhibition of cellular GSK3 by lithium or
      GSK3beta antisense elicits a reduction in Abeta. Conversely, negative modulation
      of cellular CDK5 activity by CDK5 inhibitor, roscovitine, or CDK5 antisense
      stimulates Abeta production. Neither GSK3 nor CDK5 inhibition by these means
      significantly affected cellular APP levels or APP maturation. Moreover, oral
      administration of lithium significantly reduces Abeta production whereas direct
      ICV administration of roscovitine augmented Abeta production in the brains of
      PDAPP (APP(V717F)) mice. Our data support a function for both GSK3 and CDK5 in
      APP processing, further implicating these two kinases in the pathogenesis of
      Alzheimer's disease.

PMID- 14651958
TI  - Mutagenesis of SugE, a small multidrug resistance protein.
AB  - The small multidrug resistance protein family has two subclasses. In this study
      we used a mutation approach to see what is necessary to convert a SUG subgroup
      member into a quaternary ammonium compound (QAC) transporter. We chose four key
      residues (H24, M39, I43, and A44) conserved within SUGs but conserved differently
      within the QAC transporters. Altogether, seven mutants were generated in
      Citrobacter freundii SugE. Surprisingly, the mutated SugE demonstrated an
      increased sensitivity to representative QACs. Additionally, ethidium uptake is
      found to be more prominent in the hypersensitive mutants. We conducted
      orientation studies using topology reporter gene fusions which indicated that
      SugE and the QAC transporter EmrE both have their N- and C-termini in the
      cytoplasm as predicted. The results imply that SugE can be converted to a QAC
      transporter with only a single mutation. However, because hypersensitivity was
      observed, the SugE mutant proteins are behaving as importers rather than as
      exporters.

PMID- 14651960
TI  - Regulated EGF receptor binding to F-actin modulates receptor phosphorylation.
AB  - The epidermal growth factor receptor (EGFR) is known to bind to the F-actin
      cytoskeleton in intact cells, and this interaction has been suggested to
      sequester the EGFR signal transduction system to specific loci within the cell.
      In this study, the interaction of the EGFR with actin is examined in a
      reconstituted cell free system. Soluble protein components of the cytosol from
      A431 cells are shown to dramatically enhance binding of the EGFR to F-actin in a
      saturable, concentration-dependent fashion. Most of the intracellular C-terminal
      portion of the EGFR is found to be required for this interaction. Binding of the
      EGFR to F-actin strongly deactivates the receptor by diminishing EGFR
      autophosphorylation activity and enhancing tyrosine phosphatase activity toward
      the EGFR. These results suggest that a ternary or larger protein signaling
      complex forms on an F-actin cellular scaffold, providing a spatially restricted
      signal modulation site that can be regulated by cytoskeletal remodeling.

PMID- 14651961
TI  - Prolonged culture in low glucose induces apoptosis of rat pancreatic beta-cells
      through induction of c-myc.
AB  - Prolonged culture in low-glucose concentrations (</=5mM) induces apoptosis in
      pancreatic beta-cells by a poorly defined mechanism. We now show that, in both
      purified rat beta-cells and isolated rat islets, culture in the presence of 3 or
      5mM (G3-G5) instead of 10mM glucose (G10) induces a large increase in c-myc
      expression before onset of a caspase-dependent apoptosis. These effects were
      prevented by addition of leucine and glutamine to G3 and G5, and were mimicked by
      addition of the mitochondrial poison azide to G10. In contrast, inhibition of
      Ca(2+) influx and insulin secretion with diazoxide under control conditions did
      not stimulate islet c-myc expression nor beta-cell apoptosis. In rat beta-cells,
      adenovirus-mediated c-myc overexpression increased their rate of apoptosis,
      whereas antisense-c-myc expression reduced low-glucose-induced apoptosis by
      approximately 50%. In the insulin producing MIN6 cell line, apoptosis induction
      by either low glucose or an activator of AMP-activated protein kinase (AMPK) was
      associated with c-myc mRNA and protein upregulation. In conclusion, stimulation
      of beta-cell apoptosis by prolonged culture at low glucose partly results from
      early and sustained induction of beta-cell c-myc expression. These effects may be
      due to sustained restriction in nutrient-derived metabolic signals.

PMID- 14651962
TI  - Regulation of adiponectin secretion by endothelin-1.
AB  - Adiponectin is an adipocyte-derived hormone best known for its insulin
      sensitizing ability. The expression and circulating concentration of adiponectin
      are decreased in type 2 diabetics and increase following treatment with
      thiazolidinediones. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide whose
      levels are elevated in numerous disease states, including obesity and diabetes.
      ET-1 has profound effects on adipose tissue metabolism and alters the release of
      adipose-derived factors such as leptin and resistin, therefore we investigated
      the role of ET-1 in adiponectin secretion. 3T3-L1 adipocytes were treated with
      insulin (100 nM), ET-1 (100 nM), or the appropriate vehicle and adiponectin
      secretion into the media was determined by immunoblotting and densitometric
      analysis. Adiponectin secretion significantly increased 1h following insulin or
      ET-1 treatment, respectively. Pretreatment with ET-1 for 24h significantly
      inhibited the ability of insulin or ET-1 to acutely stimulate adiponectin
      secretion. The specific ET(A) receptor antagonist, BQ-610 (1 microM),
      significantly inhibited ET-1-stimulated adiponectin secretion. In summary, ET-1
      acutely stimulates adiponectin secretion through the ET(A) receptor. Chronic
      exposure to ET-1 dramatically decreases the stimulatory effect of insulin and ET
      1 on adiponectin secretion. Our findings suggest vascular factors such as ET-1
      may play a role in the regulation of adiponectin secretion and whole body energy
      metabolism.

PMID- 14651963
TI  - Regulation of the tyrosine hydroxylase gene promoter by histone deacetylase
      inhibitors.
AB  - Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to 3,4-dihydroxy
      L-phenylalanine, which is the first and rate-limiting step in catecholamine
      biosynthesis. In the present study, we report that treatment with the histone
      deacetylase (HDAC) inhibitors, trichostatin A (TSA) or sodium butyrate,
      prominently induces the TH promoter activity in both non-neuronal and neuronal
      cell lines. By analyzing a series of deletional reporter constructs, we also
      determined that the proximal 151bp region of the TH promoter is largely
      responsible for TSA-mediated activation. Finally, we found that mutation of the
      Sp1 or CRE site, residing in the proximal area, abolishes TSA-mediated
      activation, strongly suggesting that the Sp1 and CRE sites may mediate TH
      promoter activation by inhibition of HDAC. In summary, our results provide a
      novel regulatory frame in which modulation of chromatin structure by histone
      deacetylase may contribute to transcriptional regulation of the TH via the Sp1
      and/or CRE site.

PMID- 14651964
TI  - Recombinant motor domain constructs of Chara corallina myosin display fast
      motility and high ATPase activity.
AB  - The mechanism and structural features that are responsible for the fast motility
      of Chara corallina myosin (CCM) have not been elucidated, so far. The low yields
      of native CCM that can be purified to homogeneity were the major reason for this.
      Here, we describe the expression of recombinant CCM motor domains, which support
      the fast movement of actin filaments in an in vitro motility assay. A CCM motor
      domain without light chain binding site moved actin filaments at a velocity of
      8.8 microm/s at 30 degrees C and a CCM motor domain with an artificial lever arm
      consisting of two alpha-actinin repeats moved actin filaments at 16.2 microm/s.
      Both constructs displayed high actin-activated ATPase activities ( approximately
      500 Pi/s/head), which is indicative of a very fast hydrolysis step. Our results
      provide an excellent system to dissect the specific structural and functional
      features that distinguish the myosin responsible for fast cytoplasmic streaming.

PMID- 14651965
TI  - A ribonuclease with distinctive features from the wild green-headed mushroom
      Russulus virescens.
AB  - A ribonuclease with an N-terminal sequence different from those of other
      ribonucleases has been purified from fruiting bodies of the mushroom Russula
      virescens. The RNase was adsorbed on DEAE-cellulose and Q-Sepharose in 10mM Tris
      HCl buffer (pH 7.1-7.3) and on CM-Sepharose in 10mM NH(4)OAc buffer (pH 4.6),
      unlike other mushroom ribonucleases which are unadsorbed on DEAE-cellulose. The
      RNase demonstrated a molecular mass of 28kDa in both gel filtration and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast to other mushroom
      ribonucleases which are monospecific, it exhibited co-specificity towards poly A
      and poly C. It demonstrated a pH optimum of 4.5, which is lower than values
      reported for other mushroom ribonucleases, and a temperature optimum of 60
      degrees C.

PMID- 14651966
TI  - Plasminogen-induced IL-1beta and TNF-alpha production in microglia is regulated
      by reactive oxygen species.
AB  - Microglia, major immune effector cells in the central nervous system, become
      activated during brain injury. In this study we showed that the blood component
      plasminogen/plasmin activates microglia. Plasminogen-induced IL-1beta, TNF-alpha,
      and iNOS mRNA expression in primary cultured rat microglia and BV2 murine
      microglial cells. Plasmin caused a similar response. Serine protease inhibitors
      suppressed both plasminogen- and plasmin-induced IL-1beta and TNF-alpha
      expression, indicating the importance of serine protease activity in
      plasminogen/plasmin activation of microglia. Reactive oxygen species (ROS)
      appeared to play an important role in plasminogen-induced microglial activation,
      with ROS being generated within 15min of plasminogen treatment, and antioxidants
      (100 microM trolox and 10mM NAC) reducing IL-1beta and TNF-alpha expression in
      plasminogen-treated cells. Furthermore, plasminogen stimulated CREB and NF-kappaB
      DNA binding activity, and this activation was also reduced by trolox and NAC.
      These results suggest that plasminogen activates microglia via stimulation of ROS
      production.

PMID- 14651967
TI  - Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan
      nuclear receptor ERRgamma.
AB  - Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor highly
      expressed in heart, skeletal muscle, kidney, and brain. To identify activation
      function-1 (AF-1)-dependent cofactors involved in the transcriptional function of
      ERRgamma, we screened for human cDNAs coding for proteins that bind to the
      bacterial expressed AF-1 by biopanning of a phage display library. Phages
      displaying fusion proteins with full-length PNRC2 (proline-rich nuclear receptor
      co-regulatory protein 2), already shown to be a cofactor for other nuclear
      receptors, and with a polypeptide of the bHLH corepressor TLE1 bound to the AF-1
      containing bait. Pull-down analyses demonstrated a direct interaction of the
      receptor with the newly identified full-length proteins. Surprisingly, not only
      PNRC2 but also the corepressor TLE1 functioned as ERRgamma coactivator in a
      reporter gene analysis.

PMID- 14651968
TI  - Superoxide activates a GDP-sensitive proton conductance in skeletal muscle
      mitochondria from king penguin (Aptenodytes patagonicus).
AB  - We present the partial nucleotide sequence of the avian uncoupling protein
      (avUCP) gene from king penguin (Aptenodytes patagonicus), showing that the
      protein is 88-92% identical to chicken (Gallus gallus), turkey (Meleagris
      gallopavo), and hummingbird (Eupetomena macroura). We show that superoxide
      activates the proton conductance of mitochondria isolated from king penguin
      skeletal muscle. GDP abolishes the superoxide-activated proton conductance,
      indicating that it is mediated via avUCP. In the absence of superoxide there is
      no GDP-sensitive component of the proton conductance from penguin muscle
      mitochondria demonstrating that avUCP plays no role in the basal proton leak.

PMID- 14651969
TI  - High microbial production and characterization of strictly periodic polymers
      modelled on the repetitive domain of wheat gliadins.
AB  - Primary structures of wheat prolamins contain repetitive domains involved in the
      mechanical properties of gluten. In order to experience the ability of
      recombinant strictly periodic polypeptides, modelled on a consensus sequence of
      wheat gliadins (PQQPY)(8) and (PQQPY)(17) (SPR8 and SPR17 polypeptides,
      respectively), to be formulated in film solutions, their heterologous expression
      conditions, in batch culture and low cell densities, were optimized to match the
      high requirements of this process. A convenient and general purification
      procedure was also devised. Moreover, FTIR-ATR characterizations indicated that
      these periodic polypeptides prepared as hydrated doughy state and dried have the
      tendency to form a protein network through intermolecular beta-sheets, strongly
      maintained by hydrogen bonds. Accordingly, these recombinant polypeptides are
      assumed to be a suitable candidate for potential application.

PMID- 14651970
TI  - Neonatal mortality and leanness in mice lacking the ARID transcription factor Mrf
      2.
AB  - Proteins containing the ARID (AT-rich interaction domain) DNA-binding motif
      regulate gene expression and differentiation in fungi, plants, and animals. This
      report describes phenotypes resulting from targeted disruption of the ARID gene
      Mrf-2. Homozygous loss of Mrf-2 resulted in a high rate of neonatal mortality
      that was partially strain-dependent: survival of Mrf-2(-/-) pups ranged from 6.4%
      on the 129S1 genetic background to 38% on a mixed 129S1.C57Bl/6J background. Loss
      of Mrf-2 expression did not affect embryonic survival, embryonic growth or birth
      weight. Lipid accumulation was severely reduced in brown adipose of Mrf-2(-/-)
      neonates at 24h of age, however, and Mrf-2(-/-) mice weighed significantly less
      than controls from postnatal day five onward. Adult Mrf-2(-/-) mice were lean,
      with significant reductions in brown and white adipose tissues, and in the
      percentage of body fat. Mrf-2(-/-) and Mrf-2(+/-) mice were also resistant to
      weight gains and obesity when maintained on high-fat diets. These phenotypes
      suggest that Mrf-2 is essential for accumulation of lipid stores in postnatal
      life.

PMID- 14651971
TI  - Reduction of Sulindac to its active metabolite, sulindac sulfide: assay and role
      of the methionine sulfoxide reductase system.
AB  - Sulindac is a known anti-inflammatory drug that functions by inhibition of
      cyclooxygenases 1 and 2 (COX). There has been recent interest in Sulindac and
      other non-steroidal anti-inflammatory drugs (NSAID) because of their anti-tumor
      activity against colorectal cancer. Studies with sulindac have indicated that it
      may also function as an anti-tumor agent by stimulating apoptosis. Sulindac is a
      pro-drug, containing a methyl sulfoxide group, that must be reduced to sulindac
      sulfide to be active as a COX inhibitor. In the present studies we have developed
      a simple assay to measure sulindac reduction and tested sulindac as a substrate
      for 6 known members of the methionine sulfoxide reductase (Msr) family that have
      been identified in Escherichia coli. Only MsrA and a membrane associated Msr can
      reduce sulindac to the active sulfide. The reduction of sulindac also has been
      demonstrated in extracts of calf liver, kidney, and brain. Sulindac reductase
      activity is also present in mitochondria and microsomes.

PMID- 14651972
TI  - Sulfur oxidation in Paracoccus pantotrophus: interaction of the sulfur-binding
      protein SoxYZ with the dimanganese SoxB protein.
AB  - The central protein of the sulfur-oxidizing enzyme system of Paracoccus
      pantotrophus, SoxYZ, formed complexes with subunits associated and covalently
      bound. In denaturing SDS-polyacrylamide gel electrophoresis (PAGE) SoxY migrated
      at 12 and SoxZ at 16kDa. SDS-PAGE of homogeneous SoxYZ without reductant
      separated dimeric complexes of 25, 29, and 32kDa identified by the N-terminal
      amino acid sequences as SoxY-Y, SoxY-Z, and SoxZ-Z, and subunit cleavage by
      reduction suggested their linkage via protein disulfide bonds. SoxYZ was
      reversibly redox active between -0.25 and 0.2V, as monitored by a combined
      electrochemical and FTIR spectroscopic approach. The dimanganese SoxB protein
      (58.611Da) converted the covalently linked heterodimer SoxY-Z to SoxYZ with
      associated subunits which in turn aggregated to the heterotetramer Sox(YZ)(2).
      This reaction depended on time and the SoxB concentration, and demonstrated the
      interaction of these two Sox proteins.

PMID- 14651973
TI  - Cathepsins F and S block HDL3-induced cholesterol efflux from macrophage foam
      cells.
AB  - In atherosclerosis, accumulation of cholesterol in macrophages may partially
      depend on its defective removal by high-density lipoproteins (HDL). We studied
      the proteolytic effect of cathepsins F, S, and K on HDL(3) and on lipid-free apoA
      I, and its consequence on their function as inductors of cholesterol efflux from
      cholesterol-filled mouse peritoneal macrophages in vitro. Incubation of HDL(3)
      with cathepsin F or S, but not with cathepsin K, led to rapid loss of prebeta
      HDL, and reduced cholesterol efflux by 50% in only 1min. Cathepsins F or K
      partially degraded lipid-free apoA-I and reduced its ability to induce
      cholesterol efflux, whereas cathepsin S totally degraded apoA-I, leading to
      complete loss of apoA-I cholesterol acceptor function. These results suggest that
      cathepsin-secreting cells induce rapid depletion of lipid-poor (prebeta-HDL) and
      lipid-free apoA-I and inhibit cellular cholesterol efflux, so tending to promote
      the formation and maintenance of foam cells in atherosclerotic lesions.

PMID- 14651974
TI  - Pyridoxal 5'-phosphate is a selective inhibitor in vivo of DNA polymerase alpha
      and epsilon.
AB  - Vitamin B(6) compounds such as pyridoxal 5(')-phosphate (PLP), pyridoxal (PL),
      pyridoxine (PN), and pyridoxamine (PM), which reportedly have anti-angiogenic and
      anti-cancer effects, were thought to be inhibitors of some types of eukaryotic
      DNA polymerases. PL moderately inhibited only the activities of calf DNA
      polymerase alpha (pol alpha), while PN and PM had no inhibitory effects on any of
      the polymerases tested. On the other hand, PLP, a phosphated form of PL, was
      potentially a strong inhibitor of pol alpha and epsilon from phylogenetic-wide
      organisms including mammals, fish, insects, plants, and protists. PLP did not
      suppress the activities of prokaryotic DNA polymerases such as Escherichia coli
      DNA polymerase I and Taq DNA polymerase, or DNA-metabolic enzymes such as
      deoxyribonuclease I. For pol alpha and epsilon, PLP acted non-competitively with
      the DNA template-primer and competitively with the nucleotide substrate. Since PL
      was converted to PLP in vivo after being incorporated into human cancer cells,
      the anti-angiogenic and anti-cancer effects caused by PL must have been caused by
      the inhibition of pol alpha and epsilon activities after conversion to PLP.

PMID- 14651975
TI  - GATA-4 regulates cardiac morphogenesis through transactivation of the N-cadherin
      gene.
AB  - Cardia bifida is known to occur in animal models lacking the cardiogenic
      transcriptional factor GATA-4. The downstream target genes responsible for this
      cardiac deformity remain unknown, however. Treatment with small interfering RNAs
      (siRNA) specifically targeting GATA-4 into cardiac mesodermal cells led to the
      development of cardia bifida in chick embryos. RT-PCR using mRNAs extracted from
      cardiac tubes revealed that the GATA-4-specific siRNA selectively suppresses
      expression of N-cadherin mRNA, one of the genes essential for the single heart
      formation, without affecting other cardiac marker mRNAs. Analysis of the N
      cadherin gene promoter activity using a luciferase reporter gene system and
      electrophoretic mobility shift assays revealed that GATA-4 binds directly to the
      N-cadherin gene promoter region, thereby transactivating its expression. We
      therefore concluded that the cardia bifida observed in the GATA-4-deleted model
      is caused by the transcriptional down-regulation of N-cadherin expression.

PMID- 14651976
TI  - Sperm endogenous reverse transcriptase as mediator of new genetic information.
AB  - Mature spermatozoa spontaneously take up foreign DNA molecules which can be
      delivered to embryos at fertilization. Recently we discovered an endogenous
      reverse transcriptase (RT) activity in mouse spermatozoa which can reverse
      transcribe exogenous RNA molecules into cDNA copies. Here we have sought to
      establish whether foreign RNA is a suitable substrate for the sperm RT to
      generate new functional genes. In vitro fertilization (IVF) experiments were
      carried out with spermatozoa that were preincubated with RNA from hybrid murine
      leukemia virus/virus-like 30S (MLV/VL30) beta-galactosidase (beta-gal) gene
      containing vector. The RNA was taken up by sperm cells, reverse-transcribed,
      delivered to embryos upon IVF, and propagated in a mosaic pattern in founders and
      further in the F1 progeny. beta-gal protein expression was detected in several
      tissues from both F0 and F1 animals. These results indicate that spermatozoa can
      reverse-transcribe exogenous RNA so as to generate transcriptionally competent
      sequences that are transmitted to offspring upon fertilization.

PMID- 14651977
TI  - Mutations in gp41 and gp120 of HIV-1 isolates resistant to hexa-arginine neomycin
      B conjugate.
AB  - Aminoglycoside-arginine conjugates (AACs) inhibit HIV-1 replication and act as
      Tat antagonists. AACs compete with monoclonal antibody binding to CXCR4, compete
      with SDF-1alpha and HIV-1 gp120 cellular uptake, indicating that they interfere
      with initial steps of HIV-1 infection. We here present the selection of HIV-1
      isolates resistant to hexa-arginine neomycin B conjugate (NeoR6), the most potent
      anti-HIV-1 AAC. We found in the NeoR6-resistant isolates the following mutations
      in gp120: I339T in the C3 region, S372L in the V4 region, and Q395K in the C4
      region; and in gp41: S668R and F672Y in the 'heptad repeat' 2 (HR2) region. These
      findings strongly suggest that NeoR6 obstructs HIV-1 replication by interfering
      with the fusion step, dependent on both conformational changes in gp120 following
      CD4 and CXCR4 interaction, as well as by conformational changes in gp41 induced
      by HR1 and HR2 interaction. The AACs may thus represent a novel family of fusion
      inhibitors.

PMID- 14651978
TI  - Basic calcium phosphate crystals stimulate the endocytotic activity of cells-
      inhibition by anti-calcification agents.
AB  - Pathological calcifications are associated with many medical conditions including
      diabetes, breast cancer, and crystals-associated osteoarthritis. The deposition
      of calcium-containing crystals on cells induces detrimental cellular effects and
      speeds up the progression of associated diseases. We carried out the present
      study to test the hypotheses that calcium-containing crystals may stimulate the
      influx of other molecules existing in the extracellular fluid disturbing normal
      molecular signaling and that anti-calcification agent will inhibit such
      endocytotic process. We found that basic calcium phosphate (BCP) crystals greatly
      stimulated the endocytotic activity of cells by rendering the cells more
      permeable and that the anti-calcification agent phosphocitrate and several others
      inhibited the crystals-mediated endocytosis. This is the first study reporting
      that the endocytotic activity of cells is affected by BCP crystals and that such
      endocytotic activity can be inhibited by anti-calcification agents. Since calcium
      containing crystals are associated with many human diseases and in many
      circumstances are associated with apoptotic bodies, extracellular and matrix
      vesicles where DNA fragments, small peptides, and minerals are released into
      extracellular space, the findings reported here are important for our
      understanding of the complex biological effects and the potential pathological
      role of calcium-containing crystals in crystals-associated diseases, and for the
      development of disease modifying agents as well.

PMID- 14651979
TI  - Interaction of 14-3-3 proteins with the insulin-like growth factor I receptor
      (IGFIR): evidence for a role of 14-3-3 proteins in IGFIR signaling.
AB  - We have extended our previous yeast two-hybrid findings to show that 14-3-3beta
      also interacts with the insulin-like growth factor I receptor (IGFIR) in
      mammalian cells overexpressing both proteins and that the interaction involves
      serine 1283 and is dependent on receptor activation. Treatment of cells with the
      phorbol ester PMA stimulates the interaction of 14-3-3beta with the IGFIR in the
      absence of receptor tyrosine phosphorylation, suggesting that receptor activation
      leads to activation of an endogenous protein kinase that catalyzes the
      phosphorylation of serine 1283. To investigate the role of 14-3-3 proteins in IGF
      signal transduction, IGFIR structure-function studies were performed. Mutation of
      serine 1283 alone (S1283A) (a mutation that decreases but does not abolish the
      interaction of the IGFIR with 14-3-3) did not affect anchorage-independent growth
      of NIH 3T3 fibroblasts overexpressing the mutant receptor. However, the
      simultaneous mutation of this residue and the truncation of the C-terminal 27
      residues of the receptor (Delta1310/S1283A) abolished the interaction of the
      receptor with 14-3-3 and reversed the enhanced colony formation observed with the
      IGFIR truncation mutation alone (Delta1310). The difference between the Delta1310
      and Delta1310/S1283A transfectants in the soft agar assay was confirmed by
      tumorigenesis experiments. These findings suggest that 14-3-3 proteins interact
      with the IGFIR in vivo and that this interaction may play a role in a
      transformation pathway signaled by the IGFIR.

PMID- 14651980
TI  - Effect of naturally occurring mutations in human glycine N-methyltransferase on
      activity and conformation.
AB  - Missense mutations in the enzyme, glycine N-methyltransferase (GNMT) have been
      shown to be one cause of persistent isolated hypermethioninaemia in humans. These
      mutations were first identified by metabolite analysis and were shown to be L49P,
      N140S, and H176N by gene sequencing. Here we report the kinetic and
      conformational characterization of the wild type and the three human mutant GNMTs
      expressed in Escherichia coli. Although quaternary, tertiary, and secondary
      structures of the mutant proteins are not changed, they are inactivated to
      different extents. The H176N mutation possesses 75% activity of the wild type
      enzyme while L49P has 10% activity and N140S has less than 0.5% activity of the
      wild type GNMT under the same conditions. All GNMTs display hyperbolic kinetics
      at neutral pH toward both substrates, S-adenosylmethionine and glycine. The
      turnover constants, k(cat) and Michaelis constants, K(m) for both substrates of
      all mutant proteins are considerably changed compared to the wild type enzyme.

PMID- 14651981
TI  - The basic helix-loop-helix transcription factor TAL1/SCL inhibits the expression
      of the p16INK4A and pTalpha genes.
AB  - The Tal1 gene (also called Scl or TCL5) encodes a basic helix-loop-helix
      transcription factor required for hematopoiesis and vasculogenesis. Additionally,
      aberrant transcriptional activation of the Tal1 gene is a frequent event in human
      T cell acute lymphoblastic leukemia (T-ALL). T cell specific expression of TAL1
      in mice induces aggressive T cell malignancies, demonstrating the oncogenic
      potential of TAL1. Yet, the underlying mechanisms of TAL1 induced tumorigenesis
      are poorly understood. By inhibiting E protein mediated transcription of the
      pTalpha gene, TAL1 can interfere with the T cell differentiation program. In
      addition, several studies suggest that TAL1 expression might also enhance
      proliferation rate. We report here that TAL1 can bind the E boxes in both the p16
      and the pTalpha promoters, and functionally suppress the activity of both
      promoters. These results indicate that TAL1 can affect both T cell proliferation
      and differentiation. Moreover, we show that overexpression of TAL1 in
      hematopoietic progenitor cells promotes cell cycle division.

PMID- 14651982
TI  - A protein with antimicrobial activity in the skin of Schlegel's green tree frog
      Rhacophorus schlegelii (Rhacophoridae) identified as histone H2B.
AB  - An extract of the skin of Schlegel's green tree frog, Rhacophorus schlegelii
      (Anura: Rhacophoridae), contained a protein that inhibited the growth of the Gram
      negative bacterium Escherichia coli but was inactive against the Gram-positive
      bacterium Staphylococcus aureus. The protein was purified to near homogeneity by
      reverse-phase HPLC and amino acid sequence analysis of the products of an
      endoproteinase Glu-C digest identified the protein as histone H2B. The complete
      primary structure of the 125 amino acid residue Rhacophorus histone H2B was
      determined by nucleotide sequence analysis of a cloned cDNA encoding the protein.
      Mass spectrometry demonstrated that the protein isolated from the skin was not
      post-translationally modified. Histone fragments with antimicrobial activity were
      not identified in the Rhacophorus skin extract nor were cationic, alpha-helical
      antimicrobial peptides of the kind isolated from the skins of several other frog
      families. The data provide further evidence that histones play a role in the
      defense against microorganisms.

PMID- 14651983
TI  - Hydrogen peroxide-induced phospholipase D activation and its PKC dependence are
      modulated by pH changes in PC12 cells.
AB  - Several factors for the hydrogen peroxide (H(2)O(2))-induced PLD stimulation have
      been proposed, including protein kinase C (PKC), tyrosine kinase, mitogen
      activated protein kinase and Ca(2+), but their precise roles remain to be
      defined. As for involvement of PKC, there has been some discrepancy. Our previous
      study has demonstrated that phospholipase D (PLD) activity was increased by
      exposure of PC12 cells to 0.5mM H(2)O(2) in modified Krebs-Ringer buffer (KRB)
      and suggested that the PLD activation was independent of PKC activity. However,
      we have shown here that the H(2)O(2)-induced PLD stimulation was much greatly
      enhanced by incubation in Dulbecco's modified Eagle's medium (DMEM) and further
      that it was PKC-dependent. These results indicated that the markedly enhanced PLD
      activation and its PKC dependence were modulated by pH changes during incubation
      in DMEM. Furthermore, evidence has been presented for possible involvement of
      alkaline phosphatase in this pH-dependent profile of PLD activation by H(2)O(2).

PMID- 14651984
TI  - Molecular characterization of human eye and heart fatty acid ethyl ester
      synthase/carboxylesterase by site-directed mutagenesis.
AB  - The FAEES/carboxylesterase enzyme nonoxidatively metabolizes alcohol into FAEEs,
      potentially toxic molecules linked with alcohol-induced end-organ damage. Our
      laboratory has isolated and characterized a FAEES/carboxylesterase cDNA from
      human eye and heart (G12). In an effort to further characterize the G12 enzyme,
      this laboratory has analyzed the FAEES activity, as well as performed mutagenic
      studies on a proposed active site of G12. We have mutated Ser 204 and His 451 in
      the G12 enzyme in an attempt to characterize the active site. We found that both
      mutations cause almost total loss of carboxylesterase enzyme activity with the
      native enzyme remaining active for carboxylesterase activity (560 nmol/mg
      protein/h for G12). With oleic acid as a substrate, the FAEES activity was 170
      nmol/mg protein/h for G12, 10.8 nmol/mg protein/h for M204, and 8.5 nmol/mg
      protein/h for M451. When ethanol was used as substrate, the FAEES activity was
      240 nmol/mg protein/h for G12, 15.1 nmol/mg protein/h for M204, and 6.2 nmol/mg
      protein/h for M451. Since both carboxylesterase and FAEES enzyme activities are
      significantly lowered by mutating Ser 204 and His 451 of the G12 enzyme, this
      study indicates that these residues may be important for the key enzymatic
      activities of the enzyme.

PMID- 14651985
TI  - Leptin suppresses Porphyromonas gingivalis lipopolysaccharide interference with
      salivary mucin synthesis.
AB  - Leptin, a multifunctional hormone produced predominantly by adipocytes but also
      identified throughout the glandular tissue of alimentary tract, including
      salivary glands and oral mucosa, has emerged recently as an important regulator
      of mucosal inflammatory responses to bacterial infection. In this study, we
      report that leptin prevents (up to 88.4%) the reduction in mucin synthesis evoked
      in mucous cells of sublingual salivary gland by LPS of periodontopathic
      bacterium, Porphyromonas gingivalis. The effect of leptin, moreover, was
      reflected in a marked decrease in the LPS-induced apoptosis, expression of TNF
      alpha, caspase-3 activity, and NO generation. The impedance by leptin of the LPS
      inhibitory effect on mucin synthesis was blocked by wortmannin, an inhibitor of
      PI3K, which also obviated the inhibitory effect of leptin on the LPS-induced
      upregulation in apoptosis, caspase-3 activity, and NO generation. A potentiation
      in the impedance by leptin of the LPS-induced apoptosis, caspase-3 activity, and
      NO generation was, however, attained with NOS-2 inhibitor, 1400W, that also
      caused further enhancement in the impedance by leptin of the LPS detrimental
      effect on mucin synthesis. Taken together, our data are the first to demonstrate
      the nature of the involvement of leptin in countering the pathological
      consequences of P. gingivalis infection on the synthesis of salivary mucins.

PMID- 14651986
TI  - Molecular cloning and characterization of the guinea pig
      cholinephosphotransferase gene.
AB  - Cholinephosphotransferase (CPT), the terminal enzyme in the de novo synthesis of
      phosphatidylcholine (PC), has an important role in regulating the acyl group of
      PC in mammalian cells. A 593bp cDNA coding for the 3(')-end of the CPT gene has
      been cloned from guinea pig liver using degenerative oligos based on the human
      CPT gene. It has 85% amino acid homology with the human CPT enzyme and amino acid
      variations were found to cluster at few points. Restriction enzyme polymorphisms
      were found particularly with respect to BamHI and NcoI. Hydrophobic and helix
      plot analysis of the sequence shows a similar pattern to human counterpart except
      for amino acid residues 142-179 and 173-179. PCR analysis suggested that a
      predominant pseudogene may be present in guinea pig and also the intronic
      sequences were much shorter when compared to the human CPT gene. We are the first
      to report on the C-terminal 195 amino acid residues of the CPT gene from any
      animal species alike in many aspects of cellular metabolism. The probable
      differences in genomic organization and its expression in different cancer cells
      have been discussed here having CPT as an important target for cancer drug
      development.

PMID- 14651987
TI  - Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose
      uptake in C2C12 myotubes.
AB  - To examine which branched-chain amino acids affect the plasma glucose levels, we
      investigated the effects of leucine, isoleucine, and valine (0.3 g/kg body weight
      p.o.) in normal rats using the oral glucose tolerance test (OGTT, 2 g/kg). A
      single oral administration of isoleucine significantly reduced plasma glucose
      levels 30 and 60 min after the glucose bolus, whereas administration of leucine
      and valine did not produce a significant decrease. Oral administration of valine
      significantly enhanced the plasma glucose level at 30 min after the glucose
      administration and leucine had a similar effect at 120 min. At each measurement
      timepoint, the insulin levels of the treated groups were lower than that of the
      control group. We then investigated the effects of leucine, isoleucine or valine
      at the same concentration (1 mM) on glucose metabolism in C(2)C(12) myotubes in
      the absence of insulin. Glucose consumption was elevated by 16.8% in the presence
      of 1 mM isoleucine compared with the control. Conversely, 1 mM leucine or valine
      caused no significant changes in glucose consumption in the C(2)C(12) myotubes.
      The 2-deoxyglucose uptake of C(2)C(12) myotubes significantly increased upon
      exposure to 1-10 mM isoleucine and 5-10 mM leucine. However, isoleucine caused no
      significant difference in glycogen synthesis in C(2)C(12) myotubes, although
      leucine and valine caused a significant increase in intracellular glycogen
      compared with the control. The isoleucine effect on glucose uptake was mediated
      by phosphatidylinositol 3-kinase (PI3K), but was independent of mammalian target
      of rapamycin (mTOR). These results suggest that isoleucine stimulates the insulin
      independent glucose uptake in skeletal muscle cells, which may contribute to the
      plasma glucose-lowering effect of isoleucine in normal rats.

PMID- 14651988
TI  - Expression of adiponectin receptors in pancreatic beta cells.
AB  - Pancreatic beta cell dysfunction is an early and crucial pathogenic factor in the
      development of type 2 diabetes. Free fatty acids (FFA) and adipokines released
      from adipose tissues lead to both the development of insulin resistance and beta
      cell dysfunction. Adiponectin is a novel adipokine with antidiabetic properties.
      Its circulating concentrations are reduced in subjects with increased visceral
      adiposity, insulin resistance, or type 2 diabetes. Very recently, the cloning of
      two adiponectin receptors AdipoR1 and AdipoR2 was reported. AdipoR1 is abundantly
      expressed in muscle, while AdipoR2 is predominantly expressed in liver. Here we
      report the marked expression of mRNAs for the adiponectin receptors AdipoR1 and
      AdipoR2 in human and rat pancreatic beta cells, at levels similar to liver and
      greater than muscle. Adiponectin receptor expression is increased by beta cell
      exposure to the unsaturated FFA oleate, and treatment of insulin-producing cells
      with globular adiponectin induces lipoprotein lipase expression. Regulated
      adiponectin receptor expression on pancreatic beta cells might be a novel
      mechanism modulating the effects of circulating adiponectin.

PMID- 14651989
TI  - Cloning and cell type-specific regulation of the human tyrosine hydroxylase gene
      promoter.
AB  - Tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine
      biosynthesis, is predominantly expressed in several cell groups within the brain,
      including the dopaminergic (DA) neurons of the substantia nigra and ventral
      tegmental area, and the noradrenergic neurons of the locus coeruleus. To
      investigate the regulation of cell type-specific TH expression, we cloned and
      sequenced a 5.5kb fragment of human genomic DNA immediately 5(') of the TH coding
      region. This 5(')-flanking region does not contain either a CAAT box or a GC-rich
      region, but does contain a TATA box and consensus binding sequences for basal
      (TATA and CRE), and DA neuron-specific (NBRE, Gli, and BBE) transcription
      factors. Sequence analysis showed low overall homology with the rat and mouse TH
      promoter regions, with the exception of two high-homology domains, which
      encompassed -2384 to -2323 and -123 to -65, respectively. Interestingly, these
      distal and proximal domains contained NBRE, BBE, CRE, and TATA boxes, which are
      known to play important roles in DA neurogenesis. To further localize the TH
      promoter region responsible for transcriptional activity, we fused a 3301-bp
      human TH promoter fragment (-3174 to +127) to a luciferase reporter gene, and
      used this to assess promoter activity in neuronal and non-neuronal cell lines.
      Consistent with endogenous TH expression, this promoter construct was active in
      SH-SY5Y human neuroblastoma cells but not F3 human neural stem cells (NSCs).
      Deletion analysis of TH promoter/luciferase constructs revealed the presence of
      the repressor element in -1232 to -1210 upstream of transcription initiation
      site. While this region repressed 85% of promoter activity when transfected into
      F3 cells, it was not active in SH-SY5Y cells. These data suggest that the
      repressor element may play an important role in neuron cell-specific expression
      of the TH gene. Our results may provide insight into neuronal cell-specific
      expression of the human TH gene and allow a better understanding of
      catecholaminergic neuron disorders such as Parkinson's disease and schizophrenia.

PMID- 14651990
TI  - Functional in vivo gene transfer into the myofibers of adult skeletal muscle.
AB  - The postmitotic nature and longevity of skeletal muscle fibers permit stable
      expression of any transfected gene. Direct in vivo injection of plasmid DNA, in
      both adult and regenerating muscles, is a safe, inexpensive, and easy approach.
      Here we present an optimized electroporation protocol based on the use of spatula
      electrodes to transfer cDNA in vivo into the adult myofibers of an anatomically
      defined muscle, which could be functionally characterized. In our hands, about
      80% of adult myofibers were transfected in vivo by different plasmids for GFP
      fusion proteins or for beta-galactosidase. The luciferase activity increased
      several orders of magnitude when compared to standard DNA delivery. In an
      anatomical defined muscle, the wide gene transfer was comparable to or better
      than that of retrovirus delivery, that recently has been shown to be prone to
      severe side-effects in human clinical studies. Furthermore, with our method the
      tissue damage was greatly decreased. Thus, the present work describes in vivo
      functional electrotransfer of genes in adult skeletal muscle fibers by a protocol
      that is of great potential for gene therapy, as well as for basic research.

PMID- 14651991
TI  - Isolation and characterisation of proline/arginine-rich cathelicidin peptides
      from ovine neutrophils.
AB  - Cathelicidins are a family of gene-encoded antimicrobial peptides found in
      mammals. Seven cathelicidin genes have been identified in sheep, but up to now
      only two variants of one of these predicted peptides (OaBac5) have been purified
      from ovine neutrophils. In this work numerous proline/arginine-rich cathelicidin
      peptides were purified, including the originally predicted OaBac5 and another
      OaBac5 variant. As well as this, the C-terminus of the predicted OaBac7.5 and
      various truncated forms of OaBac11 were purified. Even though these peptides were
      much smaller than those predicted, they still displayed antimicrobial activity.

PMID- 14651992
TI  - Increased atypical PKC activity in endurance-trained human skeletal muscle.
AB  - Exercise training may modulate protein content and enzyme activities in skeletal
      muscle. However, it is not known whether atypical protein kinase C (aPKC) is
      affected by training. Thus, we investigated aPKC, extracellular-regulated protein
      kinase 1/2 (ERK 1/2), and P38 mitogen-activated protein kinase (P38 MAPK)
      activities and expression in skeletal muscle from untrained and endurance-trained
      subjects at rest and after 20min of cycle exercise (80% of VO(2peak)). Activities
      of aPKC (P<0.05) and ERK 1/2 (P=0.06), but not phosphorylation of P38 MAPK, were
      higher in trained than in sedentary subjects at rest. Exercise increased the
      activities of ERK 1/2 (P<0.01) and aPKC (P<0.05) and the phosphorylation
      (Thr180/Tyr182) of P38 MAPK (P<0.01) similarly in muscle from trained and
      sedentary subjects. Protein expression of the kinases was similar in trained and
      sedentary muscle. The increased aPKC activity in exercise-trained subjects could
      be important in explaining the enhanced insulin action in these individuals.

PMID- 14651994
TI  - The SARS-CoV S glycoprotein: expression and functional characterization.
AB  - We have cloned, expressed, and characterized the full-length and various soluble
      fragments of the SARS-CoV (Tor2 isolate) S glycoprotein. Cells expressing S fused
      with receptor-expressing cells at neutral pH suggesting that the recombinant
      glycoprotein is functional, its membrane fusogenic activity does not require
      other viral proteins, and that low pH is not required for triggering membrane
      fusion; fusion was not observed at low receptor concentrations. S and its soluble
      ectodomain, S(e), were not cleaved to any significant degree. They ran at about
      180-200kDa in SDS gels suggesting post-translational modifications as predicted
      by previous computer analysis and observed for other coronaviruses. Fragments
      containing the N-terminal amino acid residues 17-537 and 272-537 but not 17-276
      bound specifically to Vero E6 cells and purified soluble receptor, ACE2, recently
      identified by M. Farzan and co-workers [Nature 426 (2003) 450-454]. Together with
      data for inhibition of binding by antibodies developed against peptides from S,
      these findings suggest that the receptor-binding domain is located between amino
      acid residues 303 and 537. These results also confirm that ACE2 is a functional
      receptor for the SARS virus and may help in the elucidation of the mechanisms of
      SARS-CoV entry and in the development of vaccine immunogens and entry inhibitors.

PMID- 14651993
TI  - Prediction of tyrosine sulfation sites in animal viruses.
AB  - Post-translational modification of proteins by tyrosine sulfation enhances the
      affinity of extracellular ligand-receptor interactions important in the immune
      response and other biological processes in animals. For example, sulfated
      tyrosines in polyomavirus and varicella-zoster virus may help modulate host cell
      recognition and facilitate viral attachment and entry. Using a Position-Specific
      Scoring-Matrix with an accuracy of 96.43%, we analyzed the possibility of
      tyrosine sulfation in all 1517 animal viruses available in the Swiss-Prot
      database. From a total of 97,729 tyrosines, we predicted 5091 sulfated tyrosine
      sites from 1024 viruses. Our site predictions in hemagglutinin of influenza A,
      VP4 of rotavirus, and US28 of cytomegalovirus strongly suggest an important link
      between tyrosine sulfation and viral disease mechanisms. In each of these three
      viral proteins, we observed highly conserved amino acid sequences surrounding
      predicted sulfated tyrosine sites. Tyrosine sulfation appears to be much more
      common in animal viruses than is currently recognized.

PMID- 14651995
TI  - Overexpression of leptin in transgenic mice leads to decreased basal lipolysis,
      PKA activity, and perilipin levels.
AB  - Transgenic mice overexpressing leptin (LepTg) exhibit substantial reductions in
      adipose mass. Since the binding of leptin to its receptor activates the
      sympathetic nervous system, we reasoned that the lean state of the LepTg mice
      could be caused by chronic lipolysis. Instead, the LepTg mice exhibited a low
      basal lipolysis state and their lean phenotype was not dependent on the presence
      of beta3-adrenergic receptors. In their white adipose tissue, protein levels of
      protein kinase A, hormone-sensitive lipase, and ADRP were not impaired. However,
      compared to normal mice, perilipin, perilipin mRNA, and cAMP-stimulated PKA
      activity were significantly attenuated. Overall, we demonstrate that the lean
      phenotype of the LepTg mice does not result in a chronically elevated lipolytic
      state, but instead in a low basal lipolysis state characterized by a decrease in
      perilipin and PKA activity in white fat.

PMID- 14651996
TI  - Neurotoxic and neurobehavioral effects of kynurenines in adult insects.
AB  - Kynurenines are endogenous metabolites of tryptophan, which are studied
      extensively in vertebrates with respect to their etiological role in the
      pathology of various neurodegenerative disorders. In insects, metabolites of the
      kynurenic pathway are present in peak concentrations in the hemolymph of
      holometabolic species during pupation and just before eclosion. Unlike in larvae,
      these compounds cause severe motor dysfunction in adult species. Adult flesh
      flies were injected with various concentrations of these endogenous toxins and
      the effects on motor function were assessed. For tryptophan, L-kynurenine, 3
      hydroxy-kynurenine, and anthranilic acid, the effects ranged from reversible to
      irreversible motor dysfunction, to instant paralysis and death. 3-Hydroxy
      anthranilic acid could induce a tetanus like spasm of the wings. Tryptophan, 3
      hydroxykynurenine, and 3-hydroxy-anthranilic acid were toxic to primary cultures
      of insect neurons. It is possible that some of these metabolites have a distinct
      role in larvae during the apoptotic events related to neurometamorphosis.

PMID- 14651997
TI  - Silibinin down-regulates survivin protein and mRNA expression and causes caspases
      activation and apoptosis in human bladder transitional-cell papilloma RT4 cells.
AB  - Bladder cancer is the fourth and eighth most common cancer in men and women in
      the United States, respectively. Survivin, a member of inhibitor of apoptosis
      protein (IAP) gene family, is deregulated in a wide range of malignancies,
      including carcinoma of the bladder urothelium. Recent advances have identified
      survivin as a novel intervention target to induce apoptosis in cancer cells by
      phytochemicals or synthetic agents. Silibinin is a naturally occurring flavanone,
      isolated from milk thistle extract, and has been shown to possess cancer
      prevention/intervention potential against various cancers. In several animal and
      human studies, it is found to be safe and non-toxic. Human bladder transitional
      cell papilloma RT4 cells were treated with silibinin and analyzed for survivin
      protein and mRNA levels by Western blotting and real-time RT-PCR, respectively.
      Silibinin treatment of cells for 24 h at 100 microM dose resulted in
      approximately 50% decrease in survivin protein level; however, treatment at 200
      microM dose for 24 and 48 h showed a complete loss in survivin protein without
      any change in actin used as loading control. Employing RT-PCR analysis we also
      observed that silibinin causes a strong to complete decrease in survivin mRNA
      levels. In other studies, down-regulation of survivin by silibinin was associated
      with a very strong and prominent caspases-9 and -3 activation as well as PARP
      cleavage. Quantitative apoptotic assay showed that silibinin decreased survivin
      levels and caspases-PARP cleavages, in accord with a strong apoptotic death and
      growth inhibition of RT4 cells. Together, these findings suggest that more
      studies are needed to investigate in vivo effect of silibinin on survivin
      expression and associated biological effects in bladder cancer that could provide
      useful information for silibinin efficacy in the prevention/intervention of human
      bladder cancer.

PMID- 14651998
TI  - Identification of novel Smad binding proteins.
AB  - The TGFbetas, a family of secreted polypeptide growth factors, are critical
      regulators of mammalian orofacial development. The importance of the TGFbetas in
      development of the orofacial region in mice is underscored by the resulting
      orofacial clefts in mice with targeted deletion of either TGFbeta2 or TGFbeta3
      and most recently, a conditional knockout of the type II TGFbeta receptor
      (TbetaRII) gene. The TGFbetas signal via binding to specific cell surface
      receptors which, in turn, activates translocation of the nucleocytoplasmic Smad
      transcriptional regulators. Smads 2 and 3 are TGFbeta-specific transcriptional
      regulators that bind DNA through their conserved MH1 domains and activate or
      inhibit transcription of TGFbeta-responsive genes through their MH2 domains. To
      search for novel Smad binding proteins expressed in developing murine orofacial
      tissue, a yeast two-hybrid assay was utilized to screen a cDNA expression library
      constructed from fetal murine orofacial tissue. Several novel Smad binding
      proteins were identified. These include a putative zinc finger protein (ZNF198),
      peroxisomal biogenesis factor 6 (Pex6), eucaryotic translation initiation factor
      4E nuclear import factor 1 (4-ET), and splicing factor 3b subunit 2 (SF3b2).
      Results of the yeast two-hybrid screen were verified by GST pull-down assays
      which confirmed the interaction of these proteins with the MH2 domain of Smad 3,
      and also indicated interaction of these proteins with additional Smad family
      members. The identification of these proteins as Smad binding partners allows
      exploration of new mechanisms whereby TGFbeta signaling may be regulated, and
      reveals additional potential interactions with other signaling pathways.

PMID- 14651999
TI  - Kir1.1 expression in embryonic kidney epithelia.
AB  - K(+) channels may regulate cell cycling, cell volume, and cell proliferation. We
      have recently shown a role for an inwardly rectifying K(+) channel,
      Kir6.1/SUR2(B), in the regulation of cell proliferation during early kidney
      development. Here, we show that the protein of a further K(+) channel, Kir1.1
      (ROMK), is also developmentally expressed in prenatal rat kidney epithelia. In
      the embryonic stage, Kir1.1 protein was localized to the plasma membrane of
      ureteric buds and collecting ducts, and of nephron stages up to the comma-shaped
      body. Experimental increase in cAMP upregulated Kir1.1b (ROMK2) mRNA abundance in
      ureteric buds. Kir1.1 protein was restricted to the distal nephron during later
      postnatal development and adulthood, as has been reported. In conclusion, we
      demonstrate redundancy of Kir channel expression in early embryonic kidney which
      could suggest that Kir1.1 acts in a similar way as Kir6.1/SUR2(B) to promote cell
      proliferation or other developmental functions.

PMID- 14652000
TI  - TIMP-1 inhibits apoptosis in breast carcinoma cells via a pathway involving
      pertussis toxin-sensitive G protein and c-Src.
AB  - In addition to inhibiting matrix metalloproteinases, tissue inhibitor of
      metalloproteinase-1 (TIMP-1) is involved in the regulation of cell growth and
      survival. To determine its mechanism of action, we investigated effects of TIMP-1
      on cell proliferation and survival and signaling pathways induced by TIMP-1 in
      the human breast carcinoma T-47D cell line. Treatment of T-47D cells with TIMP-1
      strongly inhibited apoptosis induced by serum deprivation, but did not affect
      cell proliferation. TIMP-1 induced phosphorylation of Akt and extracellular
      signal-regulated protein kinases (ERKs), but pertussis toxin and specific
      inhibitors of Src family tyrosine kinases, protein tyrosine kinases, and
      phosphatidylinositol-3 kinase (PI3 kinase) blocked the ability of TIMP-1 to
      activate Akt and ERKs as well as the anti-apoptotic effect of TIMP-1. We found
      that TIMP-1 enhanced the kinase activities of c-Src and PI3 kinase and that this
      enhancement was inhibited by pertussis toxin. Inhibition of ERK activation,
      however, resulted in a slight decrease of the TIMP-1-induced anti-apoptotic
      effect. These findings demonstrate that the ability of TIMP-1 to inhibit
      apoptosis in T-47D cells is mediated by the sequential activation of pertussis
      toxin-sensitive G protein, c-Src, PI3 kinase, and Akt.

PMID- 14652001
TI  - Diabetes impairs endothelium-dependent relaxation of human penile vascular
      tissues mediated by NO and EDHF.
AB  - Standard treatments for erectile dysfunction (ED) (i.e., PDE5 inhibitors) are
      less effective in diabetic patients for unknown reasons. Endothelium-dependent
      relaxation (EDR) of human corpus cavernosum (HCC) depends on nitric oxide (NO),
      while in human penile resistance arteries (HPRA) endothelium-derived
      hyperpolarizing factor (EDHF) and NO participate. Here we show that diabetes
      significantly reduced EDR induced by acetylcholine (ACh) in HCC and HPRA.
      Relaxation attributed to EDHF was also impaired in HPRA from diabetic patients.
      The PDE5 inhibitor, sildenafil (10nM), reversed diabetes-induced endothelial
      dysfunction in HCC, but not in HPRA. Calcium dobesilate (DOBE; 10 microM) fully
      reversed diabetes-induced endothelial dysfunction in HPRA by specifically
      potentiating the EDHF-mediated component of EDR. Impairment by diabetes of NO and
      EDHF-dependent responses precluded the complete recovery of endothelial function
      in HPRA by sildenafil. This could explain the poor clinical response to PDE5
      inhibitors of diabetic men with ED and suggests that a pharmacological approach
      that combines enhancement of NO/cGMP and EDHF pathways could be necessary to
      treat ED in many diabetic men.

PMID- 14652002
TI  - TEPP, a new gene specifically expressed in testis, prostate, and placenta and
      well conserved in chordates.
AB  - We have combined computer-based screening and experimental expression analysis to
      identify genes that are expressed in normal prostate and/or prostate cancer but
      not in essential human tissues. Using this approach we identified a new gene that
      is specifically expressed in testis, prostate, and placenta. The gene has one
      major transcript of 1.0kb in size and encodes for a protein of 30.7kDa molecular
      weight. We named this gene TEPP (expressed in testis, prostate, and placenta).
      The amino acid sequence analysis of TEPP using SignalP program shows that it has
      a signal peptide with a predicted cleavage site between amino acids 19 and 20,
      indicating that it might be a secreted protein. Analysis of the predicted TEPP
      orthologs from different species shows that these proteins are highly conserved
      in chordates. In addition we have identified a splice variant of TEPP, which
      encodes a 37kDa protein. In conclusion, a combination of bioinformatic and
      molecular approaches is useful in the identification of genes expressed in
      specific tissues. Selective expression of TEPP in testis, prostate, and in
      placenta and its high conservation among different species indicate that TEPP
      might have a role in reproductive biology.

PMID- 14652003
TI  - Incorporation of lycopene into chylomicron remnant-like particles enhances their
      induction of lipid accumulation in macrophages.
AB  - Lipid accumulation in macrophages exposed to chylomicron remnant-like particles
      containing the dietary antioxidant lycopene was investigated. After incubation
      with THP-1 macrophages (48h), chylomicron remnant-like particles containing
      lycopene (lycCRLPs) as compared to those without (CRLPs) caused significantly
      more lipid accumulation in the cells, and this was due to increases in both the
      triacylglycerol (+100%) and cholesterol (+62%) content. In addition, expression
      of mRNA for diacylglycerol acyltransferase (DGAT), a key enzyme in
      triacylglycerol synthesis, was significantly decreased by lycCRLPs, but not
      CRLPs. These findings suggest that lycopene from the diet may promote, rather
      than retard, lipid accumulation in macrophages during its transport in the blood
      in chylomicron remnants.

PMID- 14652004
TI  - Cationic liposome-mediated delivery of siRNAs in adult mice.
AB  - RNA interference mediated by small interfering RNAs (siRNAs) is a powerful tool
      for dissecting gene function and drug target validation. siRNAs can be
      synthesized in large quantities and thus can be used to analyze a large number of
      sequences emerging from genome projects in a cost-effective manner. However, the
      major obstacle to the use of siRNAs as therapeutics is the difficulty involved in
      effective in vivo delivery. We used a fluorescein-labeled siRNA to investigate
      cationic liposome-mediated intravenous and intraperitoneal delivery in adult
      mice. We show that this simple approach can deliver siRNAs into various cell
      types. In addition, we show that in contrast to mouse cells, siRNAs can activate
      the non-specific pathway in human freshly isolated monocytes, resulting in TNF
      alpha and IL-6 production. Taken together, the data provide a basis for lipid
      mediated systemic delivery of siRNAs and indicate that certain siRNA sequences
      can activate the innate immunity response genes that can be beneficial for the
      treatment of cancer.

PMID- 14652005
TI  - Expression of the murine glutathione S-transferase alpha3 (GSTA3) subunit is
      markedly induced during adipocyte differentiation: activation of the GSTA3 gene
      promoter by the pro-adipogenic eicosanoid 15-deoxy-Delta12,14-prostaglandin J2.
AB  - The expression of class alpha, micro, and pi glutathione S-transferases (GSTs)
      has been examined during the adipose conversion of mouse 3T3-L1 cells. The GSTA4,
      GSTM1, and GSTP1/2 subunits are expressed constitutively in confluent 3T3-L1
      cells, and their levels remain essentially unchanged during adipocyte
      differentiation. By contrast, the GSTA3 subunit is virtually undetectable in
      confluent 3T3-L1 cells under basal conditions, but its expression is markedly
      induced during adipose conversion. Inhibition of the 3T3-L1 adipogenic program
      demonstrated that GSTA3 expression is associated specifically with acquisition of
      the adipocytic phenotype. Reporter gene assays demonstrated that the mouse GSTA3
      5(')-upstream region is transcriptionally activated by 15-deoxy-Delta(12,14)
      prostaglandin J(2) through an antioxidant response element, suggesting that this
      pro-adipogenic eicosanoid may be involved in regulating GSTA3 expression during
      adipogenesis. These data suggest a previously unrecognised role for GSTs in mouse
      adipocytes.

PMID- 14652006
TI  - Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B
      and T lymphocyte attenuator required for association with protein tyrosine
      phosphatases SHP-1 and SHP-2.
AB  - B and T lymphocytes express receptors providing positive and negative co
      stimulatory signals. We recently identified a novel co-stimulatory molecule, B
      and T lymphocyte attenuator (BTLA), which exerts inhibitory effects on B and T
      lymphocytes. The cytoplasmic domain of murine and human BTLA share three
      conserved tyrosine-based signaling motifs, a Grb-2 recognition consensus, and two
      immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Phosphorylation of the
      cytoplasmic domain of BTLA induced the association with the protein tyrosine
      phosphatases SHP-1 and SHP-2. Association of SHP-1 and SHP-2 to other receptors
      can involve recruitment to either a single receptor ITIM or to two receptor
      ITIMs. Here, we analyzed the requirements of BTLA interaction with SHP-1 and SHP
      2 in a series of murine and human BTLA mutants. For human BTLA, mutations of
      either Y257 or Y282, but not Y226, abrogated association with both SHP-1 and SHP
      2. For murine BTLA, mutation of either Y274 or Y299, but not Y245, also abrogated
      association with both SHP-1 and SHP-2. These results indicate that for both
      murine and human BTLA, association with SHP-1 or SHP-2 requires both of conserved
      ITIM motifs and does not involve the conserved Grb-2 consensus. Thus, similar to
      the bisphosphoryl tyrosine-based activation motif (BTAM) by which the Grb-2
      associated binder (Gab1), PDGF receptor, and PECAM-1 recruit SHP-2, BTLA also
      relies on dual ITIMs for its association with the phosphatases SHP-1 and SHP-2.

PMID- 14652007
TI  - The polyglycine and polyglutamine repeats in the androgen receptor gene in
      Japanese and Caucasian populations.
AB  - Human androgen receptor (AR) gene contains two polymorphic trinucleotide repeats
      of CAG and GGC, which code for polyglutamine and polyglycine tracts in the N
      terminal domain in which the receptor activity resides. Longer repeats induce
      decrease of transactivation function in the AR receptor, weaken an anti
      proliferative effect on various steroid-related tissues, and may promote the
      carcinogenesis of these cancers, such as breast, endometrial, and ovarian
      cancers. However, the incidences of these steroid-related cancers are remarkably
      lower in Japanese than in Caucasians. We hypothesize that the GGC and CAG repeats
      in AR gene correspond to lower incidence of steroid-related cancers in the
      Japanese population. To test this hypothesis, these two polymorphic trinucleotide
      repeats in AR gene were genotyped in 221 Japanese and 177 Caucasians. The results
      of genotyping in these loci clearly show that the distribution of GGC repeat is
      significantly different between these populations (P<0.001). Japanese (73.7%) had
      16 GGC repeats compared to 53.3% for Caucasians. Japanese (3.8%) also had 17 GGC
      repeats compared to 36.2% for Caucasians. No Japanese had more than 18 GGC
      repeats compared to 3.4% for Caucasians. The length of CAG repeats in the
      Japanese population was not significantly different than that of the Caucasian
      population, although the CAG repeats varied from 14 to 31 and 15 to 29 repeats in
      Japanese and German populations, respectively. This study demonstrates that the
      Japanese population has shorter GGC compared to the Caucasian population, which
      may explain the incidences of estrogen-related cancers in these populations.

PMID- 14652008
TI  - TNF-alpha and IL-4 regulate expression of IL-13 receptor alpha2 on human
      fibroblasts.
AB  - Two interleukin 13 receptors (IL-13Rs) have been identified as IL-13Ralpha1 and
      IL-13Ralpha2. IL-13Ralpha1 is composed of a heterodimer consisting of IL
      13Ralpha1 and IL-4 receptor alpha (IL-4Ralpha) as a signaling subunit. In
      contrast, IL-13Ralpha2 is known as a decoy receptor for IL-13. In this study, we
      investigated the expression of IL-13Rs on human fibroblasts. IL-13Ralpha2 was
      significantly up-regulated after stimulation with tumor necrosis factor-alpha
      (TNF-alpha) and/or IL-4. In contrast, IL-13Ralpha1 was constitutively detectable
      and was not up-regulated. After the induction of IL-13alpha2 by IL-4, STAT6
      phosphorylation through IL-13Ralpha1 by IL-13 was inhibited. We also detected
      large intracellular pools of IL-13Ralpha2 in fibroblasts quantitatively.
      Furthermore, mobilization of the IL-13Ralpha2 protein stores from the cytoplasm
      to the cell surface was prevented by an inhibitor of protein transport, brefeldin
      A. These results indicate that TNF-alpha and IL-4 synergistically up-regulate the
      expression of IL-13Ralpha2 decoy receptor on human fibroblasts by inducing gene
      expression and mobilizing intracellular receptors, and thus may down-regulate the
      IL-13 signaling.

PMID- 14652009
TI  - Cloning of laminin gamma2 cDNA and chromosome mapping of the genes for the dog
      adhesion ligand laminin 5.
AB  - Overexpression of the gamma2 chain of laminin-5 has been linked to tumor invasion
      and an unfavorable prognostic value, but the role of this adhesion molecule in
      cancer progression remains unclear. Because dog models of human cancers provide
      the opportunity of clarifying the relation between laminin-5 and tumor malignancy
      we have isolated and characterized the cDNA of dog gamma2 chain. Comparative
      analysis of the nucleotide sequence revealed high identity between the dog and
      the human gamma2, including the intermolecular molecule binding sites and the
      regulatory promoter sequences. Moreover, expression of a recombinant human gamma2
      chain in dog keratinocytes results in assembly and secretion of hybrid laminin-5
      molecules, which underscore the functional relevance of the gamma2 conserved
      domains. We have also determined the syntenic location of the dog laminin-5 loci
      on CFA7. Our study provides a basis for therapeutical approaches of epithelial
      cancers of gamma2 using dogs as large animal models.

PMID- 14652010
TI  - WD dipeptide motifs and LXXLL motif of chicken HIRA are necessary for
      transcription repression and the latter motif is essential for interaction with
      histone deacetylase-2 in vivo.
AB  - We previously reported not only that chicken HIRA, a homolog of Saccharomyces
      cerevisiae transcriptional corepressors Hir1p and Hir2p, possesses seven WD
      dipeptide motifs and a LXXLL motif in its N-terminal half and C-terminal half,
      respectively, but also that the N-terminal and C-terminal halves, respectively,
      bind to CAF-1p48 and HDAC-1 and -2 in vitro. Seven WD dipeptide motifs in the N
      terminal half of HIRA are required for the in vitro interaction with CAF-1p48.
      The LXXLL motif at positions 993-997 of HIRA is necessary for the in vitro
      interaction with HDAC-2. Here we revealed not only that the N-terminal and C
      terminal halves of HIRA mediate individually transcription repressions but also
      that even one of the seven WD dipeptide motifs and the LXXLL motif of HIRA are
      essential for the mediations in vivo. Moreover, the LXXLL motif is essential for
      the interaction with endogenous or recombinant HDAC-2 in vivo, probably resulting
      in formation of the active complex, harboring the HDAC activity. Taken together,
      these results indicate that HIRA should participate differentially in a number of
      DNA-utilizing processes, including transcription repressions, through
      interactions of its distinct regions with CAF-1p48 and HDAC-2, respectively.

PMID- 14652011
TI  - p19ARF-induced p53-independent apoptosis largely occurs through BAX.
AB  - Combined disruption of the ARF gene and the p53 gene causes mouse predisposition
      to tumors of a wider variety and at a higher frequency than disruption of the p53
      gene, indicating that the ARF gene has p53-independent anti-tumor function in
      addition to p53-dependent function. Coincidentally with this notion, ectopic
      expression of the p19(ARF) induces apoptosis for wild-type mouse embryo
      fibroblasts which have been immortalized by introduction of the SV40 virus genome
      (SV40-MEFs). The protein expression levels of p53, p21(Cip1), and Bax were not
      upregulated by ectopic expression of p19(ARF) in SV40-MEFs, indicating that
      expression of p19(ARF) induced apoptosis through p53-independent pathways in this
      system. Ectopic expression of p19(ARF) induced prominent apoptosis even in SV40
      Bak-/-MEFs. In contrast, expression of p19(ARF) induced only a very low grade of
      apoptosis in Bax-/- or Bax-/-/Bak-/-SV40-MEFs. Remarkable attenuation of p19(ARF)
      induced apoptosis by disruption of the Bax gene thus leads to the conclusion that
      Bax plays a major role in p53-independent apoptosis induced by p19(ARF).

PMID- 14652012
TI  - Computational differentiation of N-terminal signal peptides and transmembrane
      helices.
AB  - Signal peptides and transmembrane helices both contain a stretch of hydrophobic
      amino acids. This common feature makes it difficult for signal peptide and
      transmembrane helix predictors to correctly assign identity to stretches of
      hydrophobic residues near the N-terminal methionine of a protein sequence. The
      inability to reliably distinguish between N-terminal transmembrane helix and
      signal peptide is an error with serious consequences for the prediction of
      protein secretory status or transmembrane topology. In this study, we report a
      new method for differentiating protein N-terminal signal peptides and
      transmembrane helices. Based on the sequence features extracted from hydrophobic
      regions (amino acid frequency, hydrophobicity, and the start position), we set up
      discriminant functions and examined them on non-redundant datasets with jackknife
      tests. This method can incorporate other signal peptide prediction methods and
      achieve higher prediction accuracy. For Gram-negative bacterial proteins, 95.7%
      of N-terminal signal peptides and transmembrane helices can be correctly
      predicted (coefficient 0.90). Given a sensitivity of 90%, transmembrane helices
      can be identified from signal peptides with a precision of 99% (coefficient
      0.92). For eukaryotic proteins, 94.2% of N-terminal signal peptides and
      transmembrane helices can be correctly predicted with coefficient 0.83. Given a
      sensitivity of 90%, transmembrane helices can be identified from signal peptides
      with a precision of 87% (coefficient 0.85). The method can be used to complement
      current transmembrane protein prediction and signal peptide prediction methods to
      improve their prediction accuracies.

PMID- 14652013
TI  - 26S proteasome subunits are O-linked N-acetylglucosamine-modified in Drosophila
      melanogaster.
AB  - The O-linked glycosylation of highly purified Drosophila 26S proteasome has been
      analyzed by immunological and lectin-binding methods. Five regulatory complex
      subunits and at least nine catalytic core subunits were recognized by two
      different monoclonal antibodies specific for O-linked N-acetylglucosamine
      modified proteins, and by wheat germ agglutinin, which is specific for the N
      acetylglucosamine sugar side-chain. The specificity of these reactions has been
      proved by competition studies with free N-acetylglucosamine. Three ATPase
      subunits of the regulatory complex, which are O-glycosylated, have previously
      been shown [FEBS Lett. 430 (1998) 269] to occur in phosphorylated form as well,
      indicating that several different post-translational modifications, with distinct
      regulatory potential, may be present on the same subunit.

PMID- 14652014
TI  - A real-time PCR for SARS-coronavirus incorporating target gene pre-amplification.
AB  - An enhanced polymerase chain reaction (PCR) assay to detect the coronavirus
      associated with severe acute respiratory syndrome (SARS-CoV) was developed in
      which a target gene pre-amplification step preceded TaqMan real-time fluorescent
      PCR. Clinical samples were collected from 120 patients diagnosed as suspected or
      probable SARS cases and analyzed by conventional PCR followed by agarose gel
      electrophoresis, conventional TaqMan real-time PCR, and our enhanced TaqMan real
      time PCR assays. An amplicon of the size expected from SARS-CoV was obtained from
      28/120 samples using the enhanced real-time PCR method. Conventional PCR and real
      time PCR alone identified fewer SARS-CoV positive cases. Results were confirmed
      by viral culture in 3/28 cases. The limit of detection of the enhanced real-time
      PCR method was 10(2)-fold higher than the standard real-time PCR assay and 10(7)
      fold higher than conventional PCR methods. The increased sensitivity of the assay
      may help control the spread of the disease during future SARS outbreaks.

PMID- 14652016
TI  - Crystal structure of the Kunitz (STI)-type inhibitor from Delonix regia seeds.
AB  - The three-dimensional structure of a novel Kunitz (STI) family member, an
      inhibitor purified from Delonix regia seeds (DrTI), was solved by molecular
      replacement method and refined, respectively, to R(factor) and R(free) values of
      21.5% and 25.3% at 1.75A resolution. The structure has a classical beta-trefoil
      fold, however, differently from canonical Kunitz type (STI) inhibitors, its
      reactive site loop has an insertion of one residue, Glu68, between the residues
      P1 and P2. Surprisingly, DrTI is an effective inhibitor of trypsin and human
      plasma kallikrein, but not of chymotrypsin and tissue kallikrein. Putative
      structural grounds of such specificity are discussed.

PMID- 14652015
TI  - Characterization of two different 2-oxoglutarate:ferredoxin oxidoreductases from
      Hydrogenobacter thermophilus TK-6.
AB  - A thermophilic, chemolithoautotrophic hydrogen-oxidizing bacterium,
      Hydrogenobacter thermophilus TK-6, fixes carbon dioxide via the reductive TCA
      cycle. 2-Oxoglutarate:ferredoxin oxidoreductase (OGOR) is one of the key enzymes
      of this cycle. Strain TK-6 has two distinct OGOR enzymes termed For and Kor.
      These enzymes were purified and characterized following heterologous expression
      in Escherichia coli. The specific activity of For was approximately one-tenth of
      that of Kor. Additionally, For showed higher thermo-stability than Kor under both
      aerobic and anaerobic conditions. Western blot analysis showed that both of For
      and Kor were expressed when strain TK-6 was grown under aerobic conditions. In
      contrast, only Kor was expressed when the strain was grown under anaerobic
      conditions using nitrate as a terminal electron acceptor. These results indicate
      that For supports the optimal growth of strain TK-6 in the presence of oxygen.

PMID- 14652017
TI  - Sialyl-Tn antigen expression and O-linked GalNAc-Thr synthesis by Trypanosoma
      cruzi.
AB  - Most Trypanosoma cruzi O-glycans are linked to Thr/Ser residues via N
      acetylglucosamine. We report that the mucin-type carcinoma-associated sialyl-Tn
      antigen (NeuAc-GalNAc-O-Ser/Thr) is expressed by T. cruzi. A specific MAb allowed
      us to localize the antigen on the surface of epimastigotes and to identify
      reactive components in parasite lysates (32, 60, and 94kDa). In addition,
      ppGalNAc-T activity was characterized in epimastigotes, and direct evidence was
      obtained for the in vitro incorporation of GalNAc to a synthetic peptide derived
      from a T. cruzi mucin. These results add an as yet unknown complexity to the
      pathways of O-glycan biosynthesis in this protozoan parasite.

PMID- 14652018
TI  - Activation and significance of vacuolar H+-ATPase in Saccharomyces cerevisiae
      adaptation and resistance to the herbicide 2,4-dichlorophenoxyacetic acid.
AB  - The stimulation of the activity of the H(+)-ATPase present in the vacuolar
      membrane (V-ATPase) of Saccharomyces cerevisiae is here described in response to
      a moderate stress induced by 2,4-dichlorophenoxyacetic acid (2,4-D). This in vivo
      activation (up to 5-fold) took place essentially during the adaptation period,
      preceding cell division under herbicide stress, in coordination with a marked
      activation of plasma membrane H(+)-ATPase (PM-ATPase) (up to 30-fold) and the
      decrease of intracellular and vacuolar pH values, suggesting that activation may
      be triggered by acidification. Single deletion of VMA1 and genes encoding other V
      ATPase subunits led to a more extended period of adaptation and to slower growth
      under 2,4-D stress. Results suggest that a functional V-ATPase is required to
      counteract, more rapidly and efficiently, the dissipation of the physiological
      H(+)-gradient across vacuolar membrane registered during 2,4-D adaptation.

PMID- 14652019
TI  - Interaction of scavenger receptor class B type I with peroxisomal targeting
      receptor Pex5p.
AB  - Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates
      selective HDL lipid uptake. Peroxisomes play an important role in lipid
      metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are
      translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p.
      We have previously identified a PTS1 motif in the intracellular domain of rat SR
      BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression
      of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the
      peroxisome as demonstrated by double labeling with anti-Flag IgG and anti
      catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments
      with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However,
      when an antibody against Pex5p was used for immunoprecipitation, only the 57kDa,
      non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain
      of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in
      vitro.

PMID- 14652020
TI  - Aging-associated increase of gelsolin for apoptosis resistance.
AB  - Gelsolin, a Ca(2+)-dependent actin regulatory protein, was recently suggested to
      participate in apoptosis regulation. In this study, we found that the level of
      gelsolin is elevated in senescent human diploid fibroblasts (HDFs) and also in
      the tissues of old rats, i.e., in the liver, kidney, heart, spleen, stomach, and
      brain, etc. The ubiquitous increase of gelsolin in the aged organs and cells led
      us to assume that it might be related with one of the cardinal senescent
      phenotypes, aging-associated apoptosis resistency. Thus, we tested the
      sensitivity of senescent cells to apoptosis by menadione, an apoptosis-inducing
      agent, before and after the down-regulation of gelsolin. The down-regulation of
      gelsolin in senescent HDFs, independently of Bcl-2 family expression, resulted in
      an increased sensitivity to menadione-induced apoptotic cell death. The observed
      ubiquitous increase of gelsolin in the senescent states of cells and tissues, and
      the increased sensitivity to apoptosis-induction by gelsolin down-regulation,
      suggests that gelsolin would be partly responsible for age-related apoptosis
      resistance.

PMID- 14652021
TI  - Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and
      proteasome inhibition.
AB  - Mutations in DJ-1 gene have been linked to autosomal recessive early onset
      parkinsonism (AR-EOP). Although the mechanism of neuronal cell death due to DJ-1
      mutation has not been fully elucidated, loss of DJ-1 function was considered to
      cause the phenotype. Here, we demonstrated that the down regulation of endogenous
      DJ-1 of the neuronal cell line by siRNA enhanced the cell death which was induced
      by oxidative stress, ER stress, and proteasome inhibition, but not by pro
      apoptotic stimulus. The cell death with hydrogen peroxide was dramatically
      rescued by over-expression of wild-type DJ-1, but not by that of L166P mutant DJ
      1. Furthermore, DJ-1 rescued the cell death caused by over-expression of Pael
      receptor, which was a substrate of Parkin, another gene product for autosomal
      recessive juvenile parkinsonism. These results suggest that loss of protective
      activity of DJ-1 from neuro-toxicity induced by these stresses contributes to
      neuronal cell death in AR-EOP with mutant DJ-1.

PMID- 14652022
TI  - Identification and characterization of a cDNA encoding a long-chain cis
      isoprenyltranferase involved in dolichyl monophosphate biosynthesis in the ER of
      brain cells.
AB  - A long-chain cis-isoprenyltransferase (cis-IPTase) located in the endoplasmic
      reticulum (ER) catalyzes the chain elongation stage in the pathway for the de
      novo biosynthesis of dolichyl monophosphate (Dol-P) in eukaryotic cells. In
      Saccharomyces cerevisiae, the ER-associated cis-IPTase is encoded by the RER2
      gene. Mutations in the RER2 gene result in defects in growth and protein N
      glycosylation. In this study a cDNA isolated from human brain (Accession No.
      AK023164.1), which has substantial homology to cis-IPTases from bacteria,
      Arabidopsis, and S. cerevisiae, has been shown to: (1) complement the growth
      defect; (2) restore cis-IPTase activity; dolichol and Dol-P synthesis; and (3)
      restore normal N-glycosylation of carboxypeptidase Y (CPY) in the yeast rer2Delta
      mutant. Consistent with a role in Dol-P biosynthesis, overexpression of the human
      cis-isoprenyltransferase (hCIT) cDNA also suppresses the temperature-sensitive
      growth and CPY hypoglycosylation phenotypes in sec59-1 cells which are defective
      in Dol-P biosynthesis due to a temperature-sensitive mutation in dolichol kinase.
      Overexpression of hCIT in Chinese hamster ovary (CHO) cells results in a modest
      increase in cis-IPTase activity associated with microsomal fractions and the
      appearance of a new 38kDa polypeptide that co-localizes with calnexin in the ER,
      the site of Dol-P biosynthesis, even though no transmembrane domains are
      predicted by a hydropathy plot.

PMID- 14652023
TI  - The KiSS-1 receptor GPR54 is essential for the development of the murine
      reproductive system.
AB  - GPR54 is a G-protein-coupled receptor that displays a high percentage of identity
      in the transmembrane domains with the galanin receptors. The ligand for GPR54 has
      been identified as a peptide derived from the KiSS-1 gene. KiSS-1 has been shown
      to have anti-metastatic effects, suggesting that KiSS-1 or its receptor
      represents a potential therapeutic target. To further our understanding of the
      physiological function of this receptor, we have generated a mutant mouse line
      with a targeted disruption of the GPR54 receptor (GPR54 -/-). The analysis of the
      GPR54 mutant mice revealed developmental abnormalities of both male and female
      genitalia and histopathological changes in tissues which normally contain
      sexually dimorphic features. These data suggest a role for GPR54/KiSS-1 in normal
      sexual development, and indicate that study of the GPR54 mutant mice may provide
      valuable insights into human reproductive syndromes.

PMID- 14652024
TI  - Characterization and identification of Tage4 as the murine orthologue of human
      poliovirus receptor/CD155.
AB  - CD155 is a member of the immunoglobulin superfamily also known as the human
      receptor for poliovirus (PVR). Transmembrane glycoproteins related to CD155, the
      nectins, are well-characterized cell adhesion receptors displaying a high degree
      of sequence conservation across species. In contrast, CD155 belongs to the
      category of rapidly evolving genes wherefore a mouse CD155 gene distinguished by
      an affirmative extent of amino acid conservation as observed for nectins is
      absent. Consequently, the existing genetic evidence by itself is an inferior
      indicator to consider whether Tage4, a mouse orphan receptor, represents the
      murine orthologue of CD155. In the present study Tage4 cDNA was cloned from mouse
      lung and further characterized genetically. CD155 and Tage4 possess an identical
      genomic organization and reside in syntenic chromosomal regions. The Tage4
      expression pattern was explored applying a newly generated antibody. Both
      receptors, CD155 in human and Tage4 in mouse, are expressed by intestinal
      epithelia as well as by follicle associated epithelium and follicular dendritic
      cells inside Peyer's patches of the gut associated lymphoid tissue. Furthermore,
      Tage4 lacks self-adhesion capacity but binds to vitronectin, two known features
      of CD155. These data indicate that Tage4 represents the functional orthologue of
      CD155 in mouse. Therefore, we suggest to rename Tage4 into rodent CD155.

PMID- 14652025
TI  - Evidence for alternative splicing and developmental regulation of the Drosophila
      melanogaster Mgat2 (N-acetylglucosaminyltransferase II) gene.
AB  - We present a molecular study of the Drosophila melanogaster Mgat2 gene that codes
      for the N-acetylglucosaminyltransferase II. Isolation and analysis of two cDNA
      clones indicated that the gene is alternatively spliced, generating two
      transcripts of 3.3 and 2.7kb. Developmental specificity was observed between the
      two alternative transcripts during the major developmental stages of D.
      melanogaster. The deduced amino acid sequences of the two proteins show
      significant homology to the equivalent mammalian proteins, especially in the
      carboxyterminal region. In situ hybridizations in embryos and embryonic imaginal
      discs showed that the gene is expressed mainly but not exclusively in the brain.

PMID- 14652026
TI  - Do untranslated introns control Ca2+-ATPase isoform dependence on CaM, found in
      TN and PM?
AB  - Transcript splicing characterization of tomato Ca(2+)-ATPase (LCA1 gene) mRNA
      indicates that two main transcripts are differentiated in the 3(') terminal
      region. One of them contains a sequence of about 90bp that could correspond to an
      untranslated intron that displays sequence homology to calmodulin-binding
      regions. Calmodulin-binding experiments demonstrate that only one of the two
      isoforms encoded by LCA1 binds to calmodulin. Since the M(w) calculated for this
      peptide is 3.7kDa, it is suggested that the presence of this intron is accounted
      for by the difference in the sizes of the two 116- and 120-kDa isoforms, and it
      determines calmodulin regulation. This represents a new strategy for a single
      gene to produce two isoforms that are localized differently (TN and PM), and
      which are either dependent on or independent of the calmodulin, which in turn is
      either regulated by the presence or by the absence of a 90bp untranslated intron.

PMID- 14652027
TI  - Solubilization of active green fluorescent protein from insoluble particles by
      guanidine and arginine.
AB  - Expression of green fluorescent protein (GFP) in Escherichia coli (E. coli)
      resulted in only small amount of soluble and fluorescent GFP protein and hence
      most of the protein in insoluble particles. The expressed GFP in insoluble
      particles, however, was fluorescent, indicating that it is at least in part
      folded with an intact chromophore. The GFP in insoluble particles could not be
      solubilized by an aqueous (denaturant-free) buffer. Solubilization of active GFP
      from insoluble particles was then attempted with guanidine hydrochloride
      (GdnHCl), a strong protein-denaturant, or L-arginine, an aggregation suppressor.
      Solubilization from insoluble particles by 6M GdnHCl led to complete denaturation
      of the GFP existing in insoluble particles, while GdnHCl solution at lower
      concentration could solubilize fluorescent GFP. Solubilization of fluorescently
      active GFP from insoluble particles was also achieved by L-arginine. It is
      noteworthy that L-arginine was stronger in solubilizing insoluble GFP than GdnHCl
      below 2M. These results demonstrate that some proteins expressed in E. coli may
      form insoluble particles containing native conformation and L-arginine may be
      used to recover the proteins in the native form from such insoluble particles.

PMID- 14652028
TI  - At the cutting edge of history.

PMID- 14652036
TI  - The first President of the Royal Society.
AB  - Few people know the name of the Royal Society's first President, even though he
      features prominently in Thomas Sprat's famous allegorical frontispiece. In
      promotional images, his individual identity is irrelevant for proclaiming the
      Society's allegiance to Francis Bacon and commitment to experimental
      investigation. By contrast, William Brouncker's name does appear on Peter Lely's
      large portrait, which hung at the Royal Society. Brouncker was a gifted
      mathematician as well as a conscientious administrator, and Lely's portrait
      reproduces the diagram of one of his innovative algebraic proofs.

PMID- 14652037
TI  - Exhibiting monstrosity: Chang and Eng, the 'original' Siamese twins.
AB  - Chang and Eng, the two young men who would eventually be known around the world
      as the 'original' Siamese twins, arrived in the West in 1829. They were brought
      to the West to be examined by medical men and to be exhibited to the general
      public. Throughout the 19th century in Britain and the US, 'monstrosities' such
      as Chang and Eng, as well as a host of other people with unusual anatomies, were
      considered both spectacles worthy of public display and edifying medical subjects
      with the potential to build on medical knowledge. The unique case of Chang and
      Eng illustrates that the boundary between what is of legitimate medical interest
      and what is considered merely spectacle is often blurred.

PMID- 14652038
TI  - Victorian spectacle: Julia Pastrana, the bearded and hairy female.
AB  - Julia Pastrana toured Europe in the late 1850s advertising herself as the
      'Bearded and hairy Lady' or 'Nonedescript'. She suffered from a rare inherited
      disorder, not understood until the late 20th century, which manifested itself in
      facial distortion and considerable facial hair in the male pattern. Doctors, as
      well as sensation seekers, were very keen to examine her. Her story is unusual,
      not least because she was mummified after death by her husband-manager and
      continued to tour as a mounted exhibit for a number of decades. Indirectly, she
      participated in the evolutionary debate in Britain. In 1857, when she arrived in
      Britain from America, she was popularly known as the baboon-woman. When Darwin's
      Origin of Species was published, and evolutionary controversy about ape-ancestry
      was hot in the air, she was more often likened to the gorilla or orang-utan - as
      a possible specimen of a missing link.

PMID- 14652039
TI  - Blandowski misses out: ichthyological etiquette in 19th-century Australia.
AB  - Wilhelm Blandowski, a Prussian emigre, arrived in Australia in 1849 with hopes of
      exploring and documenting the natural history of this still relatively
      scientifically nai;ve colony. After several years travelling, surveying and
      mining gold, he became the first government zoologist at the infant National
      Museum of Victoria and was a key player in the burgeoning scientific
      establishment. Chosen to lead a collecting expedition to the junction of the
      Murray and Darling Rivers in 1856, Blandowski and his faithful companion Gerard
      Krefft brought back a wealth of new material, including many species of
      undescribed freshwater fishes. Unfortunately, Blandowski's attempts to 'honour'
      members of the Philosophical Institute of Victoria backfired and a scandal
      ensued. A disillusioned Blandowski left Australia just ten years after his
      arrival. A reanalysis of his descriptions of the fish and comparison with a
      contemporary work suggests that Blandowski deserves recognition as one of
      pioneers in the natural history of Australian freshwater fish. The loss of
      taxonomic authority for eight fish species by this energetic, imaginative, but
      stubborn scientist, left the way open for future workers to make their mark,
      whereas Blandowski's name and achievements remain obscure.

PMID- 14652041
TI  - Continental drift under the Third Reich.
AB  - Contrary to what happened in many other countries in the 1930s and 1940s, Alfred
      Wegener's theory of continental drift was not generally rejected in Nazi Germany,
      although several leading German geologists of the time did not accept it. It was
      actually presented as the modern view of Earth history in books and magazine
      articles aimed at the general public. Although outlandish geological theories
      such as Horbiger's Welteislehre were favoured by some Nazi dignitaries, they were
      not widely accepted in scientific circles. On the other hand, continental drift
      received official support under the Third Reich, at a time when it was ignored or
      ridiculed by most earth scientists outside Germany.

PMID- 14652040
TI  - Race-mixing and science in the United States.
AB  - Scientific racism was widely used as a justification to oppose race-mixing in the
      United States. Historians have justly criticized this abuse of science, but have
      overlooked some of the important ways in which science was used in the 1930s and
      1940s to overturn scientific racism and opposition to race-mixing. Of particular
      importance was the cultural anthropology of Franz Boas and the evolutionary
      biology of Theodosius Dobzhansky, which supplied arguments against racism and
      fundamentally altered the scientific understanding of race.

PMID- 14652042
TI  - The Ancient Mariner and the transit of Venus.
AB  - The achievements of William Wales FRS - astronomer, classical scholar,
      demographer, editor, mathematician, meteorologist and humane teacher - have been
      overshadowed by the fame of Cook's extraordinary voyages, and overlooked as a
      significant influence on Samuel Taylor Coleridge's early development. The Royal
      Society sent Wales to Hudson Bay, Canada, and James Cook to Tahiti, both to
      observe the 1769 transit of Venus as part of an international project to
      calculate solar parallax, and hence the distance to the Sun. Wales later taught
      mathematics and navigation science at Christ's Hospital School to a precocious
      Coleridge, whose creative mind translated tales of polar adventures into
      memorable poetry.

PMID- 14652043
TI  - Perceived stress following race-based discrimination at work is associated with
      hypertension in African-Americans. The metro Atlanta heart disease study, 1999
      2001.
AB  - There is increasing evidence of an association between stress related to job
      strain and hypertension. However little data exist on stress from racism and race
      based discrimination at work (RBDW). The objective of this study was to
      investigate whether blood pressure (BP) outcomes are positively associated with
      stressful racism towards African-Americans from non-African-Americans as well as
      RBDW from other African-Americans. The metro Atlanta heart disease study was a
      population-based study which included 356 African-American men and women, aged
      >/=21 years, residing in metropolitan Atlanta, Georgia during 1999-2001.
      Perceived stress was self-reported by 197 participants for racism from non
      African-Americans and 95 for RBDW from other African-Americans. Sitting systolic
      (SBP) and diastolic (DBP) BP were taken at a clinic visit and was the average of
      the last two of three BP measures. Hypertension was self-reported as physician
      diagnosed high BP on 2 or more visits. Logistic and least-squares linear
      regression models were fit accordingly and separately for each type of stress,
      adjusting for age, gender, body mass index, and coping abilities. The likelihood
      of hypertension significantly increased with higher levels of perceived stress
      following racism from non-African-Americans, but not from RBDW from other African
      Americans; adjusted odd ratios (95% CI) were 1.4 (1.0, 1.9) and 1.2 (0.8, 1.5)
      per unit increment of stress. The adjusted magnitude of SBP and DBP increase
      between low and very high level of stress, conversely, was greater when RBDW
      originated from African-Americans than racism from non-African-Americans.
      Stressful racism and RBDW encounters are associated with increased SBP and DBP
      and increased likelihood of hypertension in African-Americans. Future studies
      with a larger sample size are warranted to further explore these findings for
      mechanistic understanding and occupational policy consideration regarding stress
      risk reduction.

PMID- 14652044
TI  - The extraordinary decline of infant and childhood mortality among Palestinian
      refugees.
AB  - This article documents the levels and patterns of infant and child mortality
      among Palestinian refugees in Jordan, Lebanon and the Palestinian areas based on
      comparable data from household sample surveys conducted since 1995. The findings
      show that Palestinian refugees have clear advantage in mortality levels as
      compared to their non-refugee counterparts in every setting, and refugees living
      in the camps have similar or lower levels of mortality than their non-camp
      counterparts, other things being equal. The recent decline of infant and child
      mortality among this vulnerable segment of the Palestinian population
      demonstrates the importance of political will in halting the truncation of infant
      lives. An examination of the mortality patterns by sex and education sheds light
      on the nature of the decline currently underway.

PMID- 14652045
TI  - Distribution of distress in post-socialist Mongolia: a cultural epidemiology of
      yadargaa.
AB  - This study discusses quality of life in post-socialist Mongolia. Yadargaa, a
      fatigue-related illness in traditional Mongolian medicine, results from lifestyle
      imbalance. We examine the distribution of yadargaa and its association to
      socioeconomic changes under capitalism. Ethnographic interviews concerning
      yadargaa were conducted with health professionals, yadargaa patients, and
      laypersons. Epidemiological methods were used to identify risk groups, to
      estimate the point prevalence, and to assess the distribution of meanings and
      interpretations of yadargaa. The epidemiological sample included 194 individuals,
      half urban and half rural. Nearly half of the epidemiological sample suffered
      from yadargaa (49%). These yadargaa sufferers felt that they benefited less than
      non-yadargaa subjects from the current socioeconomic changes. Among these,
      perceived change in employment opportunities was one of the best predictors of
      yadargaa. Additionally, yadargaa sufferers were predominantly women, the elderly,
      and urban residents. Yadargaa varies greatly in presentation; Western psychiatric
      categories are only able to explain half of yadargaa cases. In conclusion,
      yadargaa strongly associates with disenfranchised groups in the capitalist
      economy. As a culturally constructed indicator of quality of life, yadargaa is a
      window into the lives of women and men in post-socialist Mongolia.

PMID- 14652046
TI  - Suicidality and cultural values among Hong Kong adolescents.
AB  - Scholars have proposed that individualistic values resulting from globalization
      are associated with increasing behavioral and emotional problems among youth in
      modernizing cultures. This study examined specific individualistic and
      traditional values in the context of suicidal ideation and behaviors in Hong Kong
      among community adolescent youths (N=2427) ages 14-18 years. Participants
      indicated the extent to which self-direction/independence and obedience/respect
      for elders were important to them. They also reported on four progressive levels
      of suicidality: whether in the last year they had experienced suicidal ideation,
      made plans for a suicide attempt, attempted suicide, and (for attemptors) made a
      serious attempt requiring medical attention. After controlling for quality of
      family relationships and depressive symptoms, at least one of the values
      predicted suicidality at all but the highest level. There were sex-specific
      associations between values and suicidality. In general, endorsement of self
      direction was correlated with reduced risk of suicidality for boys and was
      irrelevant to girls. In contrast, traditional emphases on obedience and respect
      for elders were more frequently protective against suicidality for girls and were
      inconsistent predictors for boys. The relationship between values and suicidality
      was generally independent of the effect of family relationships and depressive
      symptoms. Thus, values were associated with adolescent suicidality, but not
      consistently in the direction predicted by some theorists, and the association
      depended upon the adolescent's sex.

PMID- 14652047
TI  - Children's nutrition in Jamaica: do household structure and household economic
      resources matter?
AB  - This study assesses the influence of household structure and resource dilution
      characteristics on children's nutritional status in Jamaica. The study has two
      objectives: (1) to compare the impact of different types of household structures
      (e.g. single parent, two parent, cohabiting and extended) on child nutrition (low
      height for age); and (2) to examine whether household structure and household
      resources interact to affect child nutrition in this context. We use data from
      the Jamaica 1996 Living Standards Measurement Study Survey and a series of
      logistic regression models to test hypotheses derived from the current child well
      being literature. The results show that living in a single-parent household and a
      cohabiting household increases the odds of stunting for children. The analysis
      also indicates that children in single-parent low-income families with siblings
      and low-income extended families with siblings are more likely to have low height
      for age. The key policy implication that emerges from this study is that
      household structure is important for understanding children's nutritional
      outcomes in the Caribbean.

PMID- 14652048
TI  - The social context of reproductive health in an Egyptian hamlet: a pilot study to
      identify female genital schistosomiasis.
AB  - This pilot study is the first to identify female genital schistosomiasis (FGS) in
      an Egyptian community setting. The year-long interdisciplinary study, in a small
      hamlet (ezba), combined clinical assessment with an in-depth study of the social
      context of reproductive health. Schistosoma haematobium ova were found in 16.7%
      of women in the study (21/126). Half of the women who agreed to a full
      gynecological examination (43 of 86) had evidence of reproductive morbidity due
      to schistosomiasis, either schistosome eggs in the cervix or sandy patches,
      tissue changes in the reproductive tract. Other reproductive tract morbidities
      included infections (vaginitis 40%, chronic cervicitis 75%, pelvic inflammation
      9%) and prolapse (54%). FGS was associated with dysparunia, abnormal vaginal
      discharge, vaginal or cervical polyps, contact bleeding, vulval itching and
      chronic cervicitis. Community members recognized S. haematobium as a health
      problem, but did not believe that it affected reproductive health. Indeed, they
      had little awareness of reproductive health and the possible impact of
      reproductive morbity on women's arduous daily tasks. There was no discussion of
      any reproductive health issues (except infertility) between women or between
      spouses. The study identified a number of factors that would affect the
      identification and treatment of FGS, and reproductive health care in general; (1)
      the neglect of women's health: (2) misconceptions about reproductive health and
      family planning; and (3) limited access to, and use of formal health care. The
      paper ends with a brief discussion of the significance of our findings about FGS,
      strategies to increase awareness of FGS, and the need for future research.

PMID- 14652049
TI  - Criterion and content validity of a novel structured haggling contingent
      valuation question format versus the bidding game and binary with follow-up
      format.
AB  - Contingent valuation question formats that will be used to elicit willingness to
      pay for goods and services need to be relevant to the area they will be used in
      order for responses to be valid. A novel contingent valuation question format
      called the "structured haggling technique" (SH) that resembles the bargaining
      system in Nigerian markets was designed and its criterion and content validity
      compared with those of the bidding game (BG) and binary-with-follow-up (BWFU)
      technique. This was achieved by determining the willingness to pay (WTP) for
      insecticide-treated nets (ITNs) in Southeast Nigeria. Content validity was
      determined through observation of actual trading of untreated nets together with
      interviews with sellers and consumers. Criterion validity was determined by
      comparing stated and actual WTP. Stated WTP was determined using a questionnaire
      administered to 810 household heads and actual WTP was determined by offering the
      nets for sale to all respondents one month later. The phi (correlation)
      coefficient was used to compare criterion validity across question formats. The
      phi coefficients were SH (0.60: 95% C.I. 0.50-0.71), BG (0.42: 95% C.I. 0.29
      0.54) and the BWFU (0.32: 95% C.I. 0.20-0.44), implying that the BG and SH had
      similar levels of criterion-validity while the BWFU was the least criterion
      valid. However, the SH was the most content-valid. It is necessary to validate
      the findings in other areas where haggling is common. Future studies should
      establish the content validity of question formats in the contexts in which they
      will be used before administering questionnaires.

PMID- 14652050
TI  - The pursuit of equity in NHS resource allocation: should morbidity replace
      utilisation as the basis for setting health care capitations?
AB  - Although the English NHS has been described as a world leader in pioneering
      methods of distributing expenditure in relation to population needs, concerns
      about the legitimacy of using the current utilisation-based model to allocate
      health service resources are mounting. In this paper, we present a critical
      review of NHS resource allocation in England and demonstrate the feasibility and
      impact of using direct health estimates as a basis for setting health care
      capitations. Comparing target allocations for the inpatient treatment of coronary
      heart disease in a sample of 34 primary care trusts in contrasting locations in
      England, we find that a morbidity-based model would result in a significant shift
      in hospital resources away from deprived areas, towards areas with older
      demographic profiles and towards rural areas. Discussing the findings in relation
      to a wider policy context that is generally concerned to direct more health care
      resources towards the poor, the paper concludes by calling for greater clarity
      between the goals of health care equity and health equity. Whilst the former
      demands that the legitimate needs of demographically older populations for more
      health care resources are acknowledged, the goal of health equity requires real
      political commitment to resource broader social policy initiatives.

PMID- 14652051
TI  - User fees at a public hospital in Cambodia: effects on hospital performance and
      provider attitudes.
AB  - User-fee programs have been introduced at health care facilities in many
      developing countries. Difficulties have been encountered, however, especially at
      public hospitals. This report describes the effects of user fees introduced in
      April 1997 at a public hospital, the National Maternal and Child Health Center
      (NMCHC) of Cambodia, on patient utilization, revenue and expenditure, quality of
      hospital services, provider attitudes, low-income patients, and the government,
      by reviewing hospital data, patient and provider surveys, and provider focus
      group discussions.Before the introduction of user fees, the revenue from patients
      was taken directly by individual staff as their private income to compensate
      their low income. After the introduction of user fees, however, revenue was
      retained by the hospital, and used to improve the quality of hospital services.
      Consequently, the patient satisfaction rate for the user-fee system showed 92.7%,
      and the number of outpatients doubled. The average monthly number of delivery of
      babies increased significantly from 319 before introduction of the system to 585
      in the third year after the user-fee introduction, and the bed occupancy rate
      also increased from 50.6% to 69.7% during the same period. As patient utilization
      increased, hospital revenue increased. The generated revenue was used to
      accelerate quality improvement further, to provide staff with additional fee
      incentives that compensated their low government salaries, and to expand hospital
      services. Thus, the revenue obtained user fees created a benign cycle for
      sustainability at NMCHC. Through this process, the user-fee revenue offered
      payment exemption to low-income users, supported the government financially
      through user-fee contributions, and reduced financial support from donors.
      Although the staff satisfaction rate remained at 41.2% due to low salary
      compensation in the third year of user-fee implementation, staff's work attitude
      shifted from salary-oriented to patient-oriented-with more attention to low
      income users.

PMID- 14652052
TI  - The effects of US state income inequality and alcohol policies on symptoms of
      depression and alcohol dependence.
AB  - Mental health is likely to be influenced by contextual variables that emerge only
      at the level of the group. We studied the effect of two such group-level
      variables, within-state income inequality and alcohol tax policy, on symptoms of
      current depression and alcohol dependence in a US national sample, controlling
      for state-level and individual characteristics. A cross-sectional US national
      probability sample provided the individual-level data. State income data were
      obtained from the 1990 US census. The Gini coefficient (raw and adjusted)
      indicated income inequality. Outcome measures included current symptoms of
      depression and alcohol dependence. Controlling for individual-level variables and
      state median income, the odds of depressive symptoms was not positively
      associated with state income inequality. Controlling for individual-level
      variables, state median income and alcohol distribution method, a weak negative
      association between Gini and alcohol dependence was observed in women, but this
      association disappeared after additional adjustment for beer tax. No association
      was observed in men. Higher state beer tax was significantly associated with
      lower prevalence of alcohol dependence symptoms for both men and women. The
      results suggest that state income inequality does not increase the experience of
      alcohol dependence or depression symptoms. However, evidence was found for a
      protective effect of increased beer taxation against alcohol dependence symptoms,
      suggesting the need to further consider the impact of alcohol policies on alcohol
      use disorders.

PMID- 14652054
TI  - Labor market experience, work organization, gender inequalities and health
      status: results from a prospective analysis of US employed women.
AB  - Women's labor force participation has increased dramatically over the past
      several decades. Although previous research has documented that a wide array of
      labor market characteristics affect health, more work is needed to understand how
      women are impacted by gender-specific employment patterns and exposures. We
      examine a cohort of 659 employed women from the Baltimore Epidemiologic Catchment
      Area (ECA) study in the USA. Baseline and follow-up data collected 13 years apart
      are used to identify associations between demographic, labor market, work
      organization, and occupational gender inequality with four health outcomes:
      generalized distress, depressive syndrome, anxiety and fair or poor health. We
      also use gender-specific data on the workplace to create indicators of
      occupational gender inequality. We found wide gender inequalities in terms of pay
      and power in this sample of employed women. Financial strain was associated with
      all of our mental health outcomes with those reporting financial strain having
      increased odds of distress, depressive syndrome and anxiety for the 13 years
      prior to the interview. Workplace factors that were found to be associated with
      the four outcomes included experiencing a promotion or demotion in the 13 years
      prior to the interview; working at a large firm; and being a professional.
      Occupations where women compared to men had lower levels of job strain-domestic
      workers in private households, machine operator and transportation-showed
      increased risk for anxiety or fair/poor health. Our findings suggest that
      measuring the complexities of employment including promotion or demotion history,
      firm characteristics and even occupational gender inequality can yield important
      information about associations with health among women.

PMID- 14652053
TI  - Assessing the impact of SSRI antidepressants on popular notions of women's
      depressive illness.
AB  - This study examines how Selective Serotonin Reuptake Inhibitor (SSRI)
      antidepressants have played a contributing role in expanding categories of
      women's "mental illness" in relation to categories of "normal" behavior. We
      hypothesized that between 1985 and 2000, as Premenopausal Dysphoric Disorder
      (PMDD), postpartum depression, and perimenopausal depression were increasingly
      treated with SSRIs, popular categories of depressive illness expanded to
      encompass what were previously considered normative women's life events such as
      motherhood, menstruation, or child birth. We quantified and qualified this
      expansion through an in-depth analysis of popular representations of depressive
      illness during the time period when SSRIs were introduced. Using established
      coding methods, we analyzed popular articles about depression from a mix of
      American magazines and newspapers spanning the years 1985-2000. Through this
      approach, we uncovered a widening set of gender-specific criteria outside of the
      Diagnostic and Statistical Manual criteria for dysthymic or depressive disorders
      that have, over time, been conceived as indicative of treatment with SSRIs. Our
      results suggest that SSRI discourse may have helped shift popular categories of
      "normal/acceptable" and "pathological/treatable" womanhood, in much the same way
      that the popularity of Ritalin has shifted these categories for childhood.

PMID- 14652055
TI  - Association of self-reported religiosity and mortality in industrial employees:
      the CORDIS study.
AB  - This study examined the association between self-reported religiosity and
      mortality in industrial employees, while controlling for workplace and
      socioeconomic factors. Subjects were 3638 Jewish Israeli males who participated
      in a 12-year follow-up study. During this period 253 deaths were recorded. The
      prevalence of negative workplace and sociodemographic factors: lower education,
      non-European origin, heavy physical work, blue-collar jobs and adverse job and
      environmental conditions, was highest among religious employees, and lower in
      traditional and nonreligious employees in descending order. Using Cox's
      proportionate hazard model an age by religiosity interaction on mortality was
      uncovered. In younger employees (age <55 years) religiosity was associated with
      lower adjusted mortality, after controlling for negative workplace and
      sociodemographic factors. Compared with nonreligious employees, the hazard ratios
      for the religious and traditional employees were: 0.64 (p=0.016) and 0.39
      (p=0.118), respectively. In older employees (age >/=55 years), religiosity was
      associated with higher adjusted mortality. The corresponding hazards ratios were
      1.69 (p=0.011) and 1.08 (p=0.004), even after controlling for the above possible
      confounding variables. It was concluded that religiosity had a protective effect
      on mortality in younger employees, but the reverse was true for older employees.
      This opposite trend could not be explained by negative sociodemographic and
      workplace conditions. The possibility of involvement of yet another potent factor
      of social isolation was discussed.

PMID- 14652056
TI  - Practitioners' impressions of patients with Parkinson's disease: the social
      ecology of the expressive mask.
AB  - The expressive mask of Parkinson's disease, a reduced spontaneity, intensity, and
      fluidity of facial, bodily, and vocal expression, jeopardizes interpersonal
      interaction and quality of life. Observers have difficulty perceiving the "real"
      person behind the mask, leading to failed communication and misunderstanding. A
      social ecological explanation of this difficulty is that observers have learned
      in their daily social lives, and quite appropriately so, that expressive behavior
      reveals meaningful information about character. The premise of this study was
      that health practitioners, especially novices, would bring into the clinic their
      everyday perceptual tendencies related to deciphering character. The study
      examined novice and expert practitioners' impressions of the personality of
      patients with Parkinson's disease who were videotaped during a healthcare
      interview. It was found that practitioners, especially novices, appeared to be
      overly sensitive to expressive masking when forming impressions about patient
      extraversion. They incorrectly perceived patients with more masking to be less
      extraverted than patients with less masking. Novice practitioners were
      particularly inaccurate in their impressions of neuroticism compared to experts.
      Novices incorrectly perceived patients with more masking as being more neurotic,
      whereas experts tended to be sensitive to valid cues of neuroticism.
      Practitioners' impressions of patient conscientiousness were not sensitive to
      masking and were highly accurate.

PMID- 14652057
TI  - Social participation and coronary heart disease: a follow-up study of 6900 women
      and men in Sweden.
AB  - Few studies have examined the relationship between social, cultural and religious
      participation, political empowerment and coronary heart disease (CHD). The aim of
      this study was to examine whether low social participation, as described in a
      social participation index, predicted incidence rates of CHD. This is a follow-up
      study, from 1990-91 to 31 December 2000, of 6861 Swedish women and men, who were
      interviewed about their social participation, education, housing tenure and
      smoking habits. A social participation index was constructed, based on 18
      variables from the survey. The outcome measure was CHD morbidity and mortality.
      Respondents with a CHD incident from 1986 until interview were excluded from the
      study. Data were analysed using Cox' regression and the results are presented as
      hazard ratios (HR) with 95% confidence intervals (CI). In the sex- and age
      adjusted model there was a gradient between the social participation index and
      CHD, so that persons with low social participation had the highest risk of CHD
      with HR=2.15; CI=1.57-2.94, followed by HR=1.67; CI=1.23-2.27 for those with
      middle social participation. In the full model, when education, housing tenure
      and smoking habits were included, the increased risk of CHD for persons with low
      social participation remained high, with HR=1.69, CI=1.21-2.37. We conclude that
      persons with low social participation in the social participation index exhibited
      an increased risk of CHD that remained after adjustment for education, housing
      tenure and smoking habits.

PMID- 14652058
TI  - Knowledge and beliefs of primary care physicians, pharmacists, and parents on
      antibiotic use for the pediatric common cold.
AB  - The aim of this study is to investigate knowledge and beliefs of primary care
      physicians (e.g. family practitioners and pediatricians), pharmacists, and
      parents regarding the use of antibiotics for the pediatric common cold, using a
      self-administered questionnaire for physicians and pharmacists and a telephone
      interview for parents. This article suggests that parents' expectation for
      antibiotics is a minor factor, and health care providers' unfounded beliefs in
      the effectiveness of antibiotics and exaggeration of parents' demand for
      antibiotics may be the major contributing factor underlying antibiotic over
      prescription for the pediatric common cold in Korea. Most physicians and
      pharmacists knew the correct cause of the pediatric common cold, but majorities
      of the physicians and pharmacists believed that antibiotics could treat and
      reduce its complications. On the other hand, 34% of the parents believed that
      antibiotics could prevent complications. Seventy three per cent of the physicians
      reported that they perceived expectations for antibiotics from parents, but only
      2% of the parents reported asking their physicians for antibiotics. In summary,
      this study suggests that physicians' knowledge and faulty beliefs can be more
      important factors for inappropriate antibiotic prescription.

PMID- 14652059
TI  - A story of maladies, misconceptions and mishaps: effective management of heart
      failure.
AB  - Congestive heart failure (CHF) is a common chronic disease with effective
      therapy, yet interventions to improve outcomes have met with limited success.
      Though problems in self-management are suspected causes for deterioration, few
      efforts have been made to understand how self-management could be improved to
      enhance the lives of affected patients. We conducted semi-structured interviews
      of 19 patients with CHF treated at an urban United States hospital to elucidate
      their knowledge and beliefs about CHF and to understand what underlies their self
      care routines. A comparison of the themes generated from these interviews with
      the common-sense model for self-management of illness threats, clarifies how
      patients' perceptions and understanding of CHF affected their behaviors. Patients
      had an acute model of CHF. They did not connect chronic symptoms with a chronic
      disease, CHF, and did not recognize that these symptoms worsened over time from
      their baseline of moderate, chronic distress, to a severe state that required
      urgent care. As a consequence, they often did not manage symptoms on a routine
      basis and did not, therefore, prevent or minimize exacerbations. When they
      worsened, many patients reported barriers to reaching their physicians and most
      reported seeking care primarily in an emergency room. These in depth responses
      elucidate how the interplay between acute and chronic models of a chronic illness
      effect self-management behaviors. These factors play a previously not understood
      role in patient's efforts to understand and manage the ever-present but
      symptomatically variable chronic illness that is CHF. These new concepts
      illustrate the tools that may be needed to effectively manage this serious and
      disabling illness, and suggest possible ways to enhance the self-management
      process and ultimately improve patients' lives.

PMID- 14652060
TI  - Is going to church good or bad for you? Denomination, attendance and mental
      health of children in West Scotland.
AB  - Religiosity is often associated with mental health in adult populations, but not
      in a consistent direction. Conflicting results reflect the multidimensional
      nature of both concepts. Few studies have addressed the relationship between
      religiosity and mental health among children. In this paper, we examine the
      relation of weekly church attendance to measures of mental health for 11 year
      olds from the two main Christian denominations in West Scotland. Levels of church
      attendance were low among those affiliated with the Church of Scotland and
      relatively high among Catholics. The only mental health measure to show a similar
      relationship with church attendance in both denominations was aggression, which
      was less prevalent among weekly attenders. Self-esteem, anxiety and depression
      all demonstrated an interaction, such that weekly church attendance was
      associated either with advantage for Catholics, disadvantage for children with a
      Church of Scotland affiliation, or both. Teasing/bullying acted in a small way as
      a mediating factor in these relationships. In an education system with separate
      Catholic and 'non-denominational' schools, we hypothesise that the relationship
      between church attendance and mental health may be contingent on whether church
      attendance is normative within the peer group.

PMID- 14652061
TI  - Alt and Swartz 'task oriented nursing in tuberculosis control programme in South
      Africa: where does it come from and what keeps it going?'.

PMID- 14652062
TI  - Assessing the quality of life of patients in phases I and II anti-cancer drug
      trials: interviews versus questionnaires by Cox K.

PMID- 14652066
TI  - Cortex Pharmaceuticals, Inc. Maintaining brain function goes a long way.

PMID- 14652067
TI  - Molecular engineering of peptides.
AB  - Deeper understanding of the role of short peptides in lipid layers has revealed
      potential applications for rationally designed synthetic replacements. A recent
      report illustrates the successful design of a peptoid mimic of SP-C, a protein
      linked to respiratory distress syndrome.

PMID- 14652068
TI  - Chemical signaling among bacteria and its inhibition.
AB  - Generations of chemists and biologists have conducted research on natural
      products and other metabolites produced by bacteria and other microorganisms.
      This has led to an explosion in knowledge concerning the mechanism by which such
      natural products are made, ultimately allowing custom redesign of many of these
      molecules for increased potency and selectivity as therapeutic drugs. Along the
      way, scientists have begun to appreciate that the bacterial world is teeming with
      life on a scale hardly conceivable, with constant communication within the
      bacterial world and with outside neighbors, such as plants and mammals. Only in
      recent years have some of the signaling molecules that comprise these elaborate
      forms of communication been characterized in any sort of chemical detail, which
      has in turn peaked interest in the intricate biology of this micro-world and its
      interactions with the macro-world.

PMID- 14652069
TI  - Cooperativity, partially bound states, and enthalpy-entropy compensation.
AB  - Efforts to develop a quantitative understanding of molecular recognition rely on
      the additivity of individual intermolecular interactions, and cooperativity
      represents one of the major potential stumbling blocks. A chemical double-mutant
      cycle has been used to experimentally measure cooperativity between functional
      group interactions within a complex framework. The interaction between two
      aromatic groups varies by 0.2 +/- 0.4 kJ mol(-1) in synthetic H-bonded complexes
      that differ by 8-13 kJ mol(-1) in overall stability. In these systems, the free
      energies associated with individual intermolecular interactions can therefore be
      reliably treated in an additive fashion. The results suggest that alternative
      explanations should be considered for cooperative phenomena observed in other
      systems, and a rationale based on the population of partially bound states in
      flexible molecules is proposed to account for the enthalpic chelate effect and
      enthalpy-entropy compensation.

PMID- 14652070
TI  - Structural basis for thrombin activation of a protease-activated receptor:
      inhibition of intramolecular liganding.
AB  - Protease-activated G protein-coupled receptors (PAR1-4) are tethered-ligand
      receptors that are activated by proteolytic cleavage of the extracellular domain
      (exodomain) of the receptor. PAR1, the prototypic member of the PAR family, is
      the high-affinity thrombin receptor of platelets and vascular endothelium and
      plays a critical role in blood coagulation, thrombosis, and inflammation. Here,
      we describe the solution structure of the thrombin-cleaved exodomain of PAR1. The
      side chains of a hydrophobic hirudin-like (Hir) sequence and adjacent anionic
      motif project into solution. Docking of the exodomain Hir sequence to exosite I
      of thrombin reveals that the tethered ligand in the cleaved exodomain bends away
      from thrombin, leaving its active site available to another large macromolecular
      substrate. The N-terminal ligand is longer than anticipated and forms an
      intramolecular complex with a region located in the C terminus of the exodomain.
      Mutational analysis confirmed that this C-terminal region is a ligand binding
      site for both intra- and intermolecular ligands. A lipidated-ligand binding site
      peptide was found to be an effective inhibitor of thrombin-induced platelet
      aggregation.

PMID- 14652071
TI  - Encodamers: unnatural peptide oligomers encoded in RNA.
AB  - Conventional display libraries are generally limited to the 20 naturally
      occurring amino acids. Here, we demonstrate that novel unnatural amide-linked
      oligomers can be constructed and encoded in an attached RNA for the purpose of
      mRNA display library design. To do this, we translated templates of various
      lengths in a protein synthesis system modified to promote sense codon
      suppression. Unnatural residues were escorted to the ribosome as chemically
      acylated tRNAs added to the translation mixture. Our experiments reveal that
      unnatural peptide oligomers ("encodamers") consisting of an N-substituted amino
      acid are readily generated as mRNA-peptide fusions with excellent stepwise
      efficiency. The N-substituted polyamides have strikingly improved proteolytic
      stability relative to their naturally encoded counterparts. Overall, our work
      indicates that the ribosome can be used as a synthesis platform to generate
      encoded combinatorial chemistry outside the universal genetic code.

PMID- 14652072
TI  - Pseudopterosin biosynthesis in Symbiodinium sp., the dinoflagellate symbiont of
      Pseudopterogorgia elisabethae.
AB  - Investigations are reported that identify the biosynthetic source and origins of
      the pseudopterosins, pharmacologically important diterpene glycosides, in the
      gorgonian coral Pseudopterogorgia elisabethae. We report here the isolation of
      physiologically significant levels of endogenous pseudopterosins A, B, C, and D
      from purified symbionts identified as the dinoflagellate Symbiodinium sp.
      Biosynthetic studies in photosynthesizing symbiont isolates utilizing 14C-labeled
      inorganic carbon and the tritiated intermediate geranylgeranyl diphosphate
      yielded radiochemically pure pseudopterosins A through D and the first committed
      intermediate, elisabethatriene. The 14CO(2) uptake into the pseudopterosin
      pathway occurred at low levels compared to the 14CO(2) uptake into total lipids,
      suggesting a large reserve pool of the compounds. These results reveal for the
      first time that pseudopterosin biosynthesis is occurring within the algal
      symbiont and suggests the physiological implications of this biosynthesis.

PMID- 14652073
TI  - Helical peptoid mimics of lung surfactant protein C.
AB  - Among the families of peptidomimetic foldamers under development as novel
      biomaterials and therapeutics, poly-N-substituted glycines (peptoids) with alpha
      chiral side chains are of particular interest for their ability to adopt stable,
      helical secondary structure in organic and aqueous solution. Here, we show that a
      peptoid 22-mer with a biomimetic sequence of side chains and an amphipathic,
      helical secondary structure acts as an excellent mimic of surfactant protein C
      (SP-C), a small protein that plays an important role in surfactant replacement
      therapy for the treatment of neonatal respiratory distress syndrome. When
      integrated into a lipid film, the helical peptoid SP mimic captures the essential
      surface-active behaviors of the natural protein. This work provides an example of
      how an abiological oligomer that closely mimics both the hydrophobic/polar
      sequence patterning and the fold of a natural protein can also mimic its
      biophysical function.

PMID- 14652074
TI  - Organizational and mutational analysis of a complete FR-008/candicidin gene
      cluster encoding a structurally related polyene complex.
AB  - The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans
      137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a
      modular PKS and 15 additional genes. The extensive similarity to the partially
      characterized candicidin gene cluster in Streptomyces griseus IMRU3570,
      especially for genes involved in mycosamine biosynthesis, prompted us to compare
      the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus
      IMRU3570, and we found that FR-008 and candicidin complex are identical. A model
      for biosynthesis of a set of four structurally related FR-008/candicidin
      compounds was proposed. Deletion of the putative regulatory genes abolished
      antibiotic production, while disruption of putative glycosyltransferase and GDP
      ketosugar aminotransferase functionalities led to the productions of a set of
      nonmycosaminated aglycones and a novel polyene complex with attachment of altered
      sugar moiety, respectively.

PMID- 14652075
TI  - Using a solid-phase ribozyme aminoacylation system to reprogram the genetic code.
AB  - Here, we report a simple and economical tRNA aminoacylation system based upon a
      resin-immobilized ribozyme, referred to as Flexiresin. This catalytic system
      features a broad spectrum of activities toward various phenylalanine (Phe)
      analogs and suppressor tRNAs. Most importantly, it allows users to perform the
      tRNA aminoacylation reaction and isolate the aminoacylated tRNAs in a few hours.
      We coupled the Flexiresin system with a high-performance cell-free translation
      system and demonstrated protein mutagenesis with seven different Phe analogs in
      parallel. Thus, the technology developed herein provides a new tool that
      significantly simplifies the procedures for the synthesis of aminoacyl-tRNAs
      charged with nonnatural amino acids, which makes the nonnatural amino acid
      mutagenesis of proteins more user accessible.

PMID- 14652076
TI  - A specificity switch in selected cre recombinase variants is mediated by
      macromolecular plasticity and water.
AB  - The basis for the altered DNA specificities of two Cre recombinase variants,
      obtained by mutation and selection, was revealed by their cocrystal structures.
      The proteins share similar substitutions but differ in their preferences for the
      natural LoxP substrate and an engineered substrate that is inactive with wild
      type Cre, LoxM7. One variant preferentially recombines LoxM7 and contacts the
      substituted bases through a hydrated network of novel interlocking protein-DNA
      contacts. The other variant recognizes both LoxP and LoxM7 utilizing the same DNA
      backbone contact but different base contacts, facilitated by an unexpected DNA
      shift. Assisted by water, novel interaction networks can arise from few protein
      substitutions, suggesting how new DNA binding specificities might evolve. The
      contributions of macromolecular plasticity and water networks in specific DNA
      recognition observed here present a challenge for predictive schemes.

PMID- 14652077
TI  - A possible approach to site-specific insertion of two different unnatural amino
      acids into proteins in mammalian cells via nonsense suppression.
AB  - The site-specific insertion of an unnatural amino acid into proteins in vivo via
      nonsense suppression has resulted in major advances in recent years. The ability
      to incorporate two different unnatural amino acids in vivo would greatly increase
      the scope and impact of unnatural amino acid mutagenesis. Here, we show the
      concomitant suppression of an amber and an ochre codon in a single mRNA in
      mammalian cells by importing a mixture of aminoacylated amber and ochre
      suppressor tRNAs. This result provides a possible approach to site-specific
      insertion of two different unnatural amino acids into any protein of interest in
      mammalian cells. To our knowledge, this result also represents the only
      demonstration of concomitant suppression of two different termination codons in a
      single gene in vivo.

PMID- 14652078
TI  - Structure-based discovery of potassium channel blockers from natural products:
      virtual screening and electrophysiological assay testing.
AB  - Potassium ion (K(+)) channels are attractive targets for rational drug design.
      Based upon a three-dimensional model of the eukaryotic K(+) channels, the docking
      virtual screening approach was employed to search the China Natural Products
      Database. Compounds were ranked according to the relative binding energy,
      favorable shape complementarity, and potential of forming hydrogen bonds with the
      K(+) channel. Four candidate compounds found by virtual screening were
      investigated by using the whole-cell voltage-clamp recording in rat dissociated
      hippocampal neurons. When applied extracellularly, compound 1 markedly depressed
      the delayed rectifier K(+) current (I(K)) and fast transient K(+) current (I(A)),
      whereas compounds 2, 3, and 4 exerted a more potent and selective inhibitory
      effect on I(K). Intracellular application of the four compounds had no effect on
      both the K(+) currents.

PMID- 14652079
TI  - Using oxidative crosslinking and proximity labeling to quantitatively
      characterize protein-protein and protein-Peptide complexes.
AB  - The quantitative analysis of protein-protein and protein-peptide complexes is of
      fundamental importance in biochemistry. We report here that nickel-catalyzed
      proximity biotinylation and Ru(II)(bpy)(3)(2+)-mediated oxidative crosslinking
      can be used to measure the equilibrium dissociation constant and stoichiometry of
      protein complexes. Only small amounts of protein are required, neither of the
      binding partners must be immobilized on a surface, and no special instrumentation
      is necessary. This chemistry should provide a useful complement to existing
      methods for the analysis of protein-protein and protein-peptide interactions.

PMID- 14652080
TI  - Nickel2+-mediated assembly of an RNA-amino acid complex.
AB  - The RNA species SHR1 reacts with biocytin (epsilon-biotinoyl-L-lysine) in the
      presence of Ni(2+) or Pt(2+) to produce a metal-bridged complex that migrates
      more slowly than unreacted RNA in the presence of streptavidin (StrAv) on
      denaturing polyacrylamide gels. Mapping of reverse transcription pause sites
      identified G79 as a reactive nucleotide. G79 is near the 3' end of a 37
      nucleotide core motif that is nearly as reactive as SHR1. SHR1 reacts with
      biocytin in the presence of Pt(2+) to yield a product that comigrates with the
      Ni(2+) product but that is much more stable, suggesting that the metal ion used
      in the reaction is present in the product, possibly linking the RNA to the amino
      acid. In support of this model, SHR1 shows a strong affinity for Ni(2+) in
      immobilized metal ion chromatography.

PMID- 14652081
TI  - Clinical use of QEEG.

PMID- 14652082
TI  - Neurophysiology of swallowing.
AB  - Swallowing is a complex motor event that is difficult to investigate in man by
      neurophysiological experiments. For this reason, the characteristics of the brain
      stem pathways have been studied in experimental animals. However, the sequential
      and orderly activation of the swallowing muscles with the monitoring of the
      laryngeal excursion can be recorded during deglutition. Although influenced by
      the sensory and cortical inputs, the sequential muscle activation does not alter
      from the perioral muscles caudally to the cricopharyngeal sphincter muscle. This
      is one evidence for the existence of the central pattern generator for human
      swallowing. The brain stem swallowing network includes the nucleus tractus
      solitarius and nucleus ambiguus with the reticular formation linking synaptically
      to cranial motoneuron pools bilaterally. Under normal function, the brain stem
      swallowing network receives descending inputs from the cerebral cortex. The
      cortex may trigger deglutition and modulate the brain stem sequential activity.
      The voluntarily initiated pharyngeal swallow involves several cortical and
      subcortical pathways. The interactions of regions above the brain stem and the
      brain stem swallowing network is, at present, not fully understood, particularly
      in humans. Functional neuroimaging methods were recently introduced into the
      human swallowing research. It has been shown that volitional swallowing is
      represented in the multiple cortical regions bilaterally but asymmetrically.
      Cortical organisation of swallowing can be continuously changed by the continual
      modulatory ascending sensory input with descending motor output. SIGNIFICANCE:
      Dysphagia is a severe symptom complex that can be life threatening in a
      considerable number of patients. Three-fourths of oropharyngeal dysphagia is
      caused by neurological diseases. Thus, the responsibility of the clinical
      neurologist and neurophysiologist in the care for the dysphagic patients is
      twofold. First, we should be more acquainted with the physiology of swallowing
      and its disorders, in order to care for the dysphagic patients successfully.
      Second, we need to evaluate the dysphagic problems objectively using practical
      electromyography methods for the patients' management. Cortical and subcortical
      functional imaging studies are also important to accumulate more data in order to
      get more information and in turn to develop new and effective treatment
      strategies for dysphagic patients.

PMID- 14652083
TI  - Neural activity associated with binaural processes for the perceptual segregation
      of pitch.
AB  - OBJECTIVE: We measured late cortical potentials in a psychophysical procedure for
      binaural unmasking of a dichotically-embedded pitch. METHODS: Late-latency
      auditory evoked potentials were measured from 128 recording channels in 13
      healthy subjects. Control stimuli consisted of 500 ms segments of broadband
      acoustic noise presented identically to both ears via earphones, evoking a
      perception of noise localized in the centre of the head. Dichotic pitch stimuli
      were created by introducing a dichotic delay to a narrow frequency region of the
      same noise segments, and resulted in a perception of both the centrally-located
      noise and a right-lateralized pitch. RESULTS: Both stimuli evoked late auditory
      event-related potentials (ERPs) characterized by a P1-N1-P2 complex of waves
      between 60 and 180 ms after stimulus onset. ERPs associated with the control and
      dichotic pitch stimuli showed no amplitude differences for the P1 and N1 waves.
      ERPs to dichotic pitch stimuli became significantly more negative beginning at a
      latency around 150 ms, an effect that was maximal between 210 and 280 ms.
      Topographic mapping showed that this late negativity was lateralized to the left
      hemisphere. CONCLUSIONS: The late negative wave elicited by the dichotic pitch
      stimulus reflects neural processing that is dependent upon binaural fusion within
      the auditory system. SIGNIFICANCE: The dichotic pitch paradigm may provide a
      useful tool for the electrophysiological assessment and study of the temporal
      processing capabilities of the auditory system. This paradigm may also be useful
      for the study of binaural mechanisms for the perceptual segregation of concurrent
      sound sources.

PMID- 14652084
TI  - Changes in somatosensory evoked responses by repetition of the median nerve
      stimulation.
AB  - OBJECTIVE: We investigate the synaptic factor for the recovery function of evoked
      responses using a repetitive stimulation technique. METHODS: Somatosensory evoked
      cortical magnetic field (SEF) was recorded following stimulation of the median
      nerve using single to 6-train stimulation in 8 healthy subjects. The SEF
      responses after each stimulus in the train stimulation were extracted by
      subtraction of the waveforms. RESULTS: An attenuation of the SEF components was
      recognized after the second of the stimuli, but there was no significant
      attenuation with the third or later stimulations. The root mean square (RMS) of
      the 1M (peak latency at 20 ms after stimulation) and 4M (70 ms) components were
      smaller than that of the single stimulation during the train stimulation, while
      the 2M (30 ms) and 3M (45 ms) components were not attenuated, but the 3M was
      facilitated at the fourth to sixth stimulation. CONCLUSION: The synaptic factor
      was not responsible for the attenuation of the SEF components during repetitive
      stimulation in healthy subjects. The SEF change disclosed a functional difference
      among the SEF components during the train stimulation, especially among the later
      components.

PMID- 14652085
TI  - Human sleep spindle characteristics after sleep deprivation.
AB  - OBJECTIVE: Sleep spindles (12-15 Hz oscillations) are one of the hallmarks of the
      electroencephalogram (EEG) during human non-rapid eye movement (non-REM) sleep.
      The effect of a 40 h sleep deprivation (SD) on spindle characteristics along the
      antero-posterior axis was investigated. METHODS: EEGs during non-REM sleep in
      healthy young volunteers were analyzed with a new method for instantaneous
      spectral analysis, based on the fast time frequency transform (FTFT), which
      yields high-resolution spindle parameters in the combined time and frequency
      domain. RESULTS: FTFT revealed that after SD, mean spindle amplitude was
      enhanced, while spindle density was reduced. The reduction in spindle density was
      most prominent in the frontal derivation (Fz), while spindle amplitude was
      increased in all derivations except in Fz. Mean spindle frequency and its
      variability within a spindle were reduced after SD. When analyzed per 0.25 Hz
      frequency bin, amplitude was increased in the lower spindle frequency range (12
      13.75 Hz), whereas density was reduced in the high spindle frequency range (13.5
      14.75 Hz). CONCLUSIONS: The observed reduction in spindle density after SD
      confirms the inverse homeostatic relationship between sleep spindles and slow
      waves whereas the increase in spindle amplitude and the reduction in intra
      spindle frequency variability support the hypothesis of a higher level of
      synchronization in thalamocortical cells when homeostatic sleep pressure is
      enhanced.

PMID- 14652087
TI  - Effect of total sleep deprivation on the landmarks of stage 2 sleep.
AB  - OBJECTIVE: To assess the effects of total sleep deprivation on sleep spindle and
      K-complex (KC) density. METHODS: Eight healthy male subjects (mean age=23.4
      years) participated in the experiment: they slept in the laboratory for 3 nights
      (one adaptation, one baseline, one recovery); baseline and recovery night were
      separated by a period of 40 h of continuous wake. RESULTS: One night of total
      sleep deprivation caused a doubling of slow-wave sleep (SWS) amount, an increase
      of sleep efficiency and a reduction of the latencies of non-rapid eye movement
      (NREM) sleep stages during the recovery night. These effects were accompanied by
      a significant reduction in spindle density in the first sleep cycle of the
      recovery night. Mean KC density did not change as a result of total sleep
      deprivation, while KC density and inter-KC intervals showed linear trends across
      the first 4 sleep cycles, respectively decreasing and increasing. Finally, a
      clear evidence of an antagonist relationship between spindle and KC changes
      across sleep cycles was provided. CONCLUSIONS: The present study further supports
      the existence of a reciprocal relationship between SWS and sleep spindles, but
      fails to show an increase of KC density after total sleep deprivation. The
      opposite time courses of spindle and KC density across sleep cycles points to an
      antagonist relation between the two main phasic events of NREM sleep. The latter
      result, together with the increase of inter-KC distance and the decrease of KC
      density across subsequent sleep cycles, is consistent with the hypothesis of a
      role of the spontaneous KC as the "forerunner" of delta waves.

PMID- 14652086
TI  - The alerting effects of caffeine, bright light and face washing after a short
      daytime nap.
AB  - OBJECTIVE: The present study examined whether the combination of a short daytime
      nap with caffeine, bright light and face washing was effective against mid
      afternoon sleepiness. METHODS: Ten young healthy adults participated in 5
      experimental conditions; those experiments were-Nap only: taking a 20 min nap;
      Caffeine+Nap: taking 200 mg of caffeine followed by a nap; Nap+Bright-light:
      being exposed to 2000 lx of bright light for 1 min immediately after napping;
      Nap+Face-washing: washing their faces immediately after napping; and No-Nap:
      taking a rest without sleep. These naps were taken at 12:40 hours. The subjects
      engaged in computer tasks for 15 min before napping and for 1 h after napping.
      RESULTS: Caffeine+Nap was the most effective for subjective sleepiness and
      performance level; its effects lasted throughout 1 h after napping. Nap+Bright
      light was comparable with Caffeine+Nap, except for performance level. Nap+Face
      washing showed mild and transient effects, however, it suppressed subjective
      sleepiness immediately after napping. CONCLUSIONS: The effects of a short nap
      against mid-afternoon sleepiness could be enhanced by combining caffeine intake,
      exposure to bright light, or face washing. SIGNIFICANCE: The present study would
      provide effective countermeasures against mid-afternoon sleepiness and sleepiness
      related accidents.

PMID- 14652088
TI  - Clinical-electroencephalogram patterns at seizure onset in patients with
      hippocampal sclerosis.
AB  - OBJECTIVE: The purpose of this study is to identify specific clinical
      electroencephalogram (EEG) patterns at seizure onset in patients with hippocampal
      sclerosis (HS). METHODS: Sixty-six ictal video-EEG recordings corresponding to 26
      patients with HS have been reviewed, focusing on the EEG features found during
      the first 30 ictal s. The EEG activity has been classified into the following
      groups: (A) according to spatial distribution: type 1: temporal electrodes on one
      side; type 2: temporal and adjacent frontal electrodes on one side; and type 3:
      non-lateralizing electrographic activity; and (B) according to morphology;
      subtype (a): regular 5-9 Hz rhythmic activity (RA); subtype (b): low-voltage
      rapid activity, followed by a 5-9 Hz RA; and subtype (c): irregular EEG sharp
      waves. We analyzed the clinical symptoms sequence and established the
      relationship with the ictal EEG patterns. RESULTS: Considering spatial
      distribution and morphology, the most frequent ictal EEG patterns were type 1
      (57%), type 2 (37%), and subtype (a): 62%; subtype (b): 27%; and subtype (c):
      11%. The sequence of clinical symptoms observed was: aura-->behavioral arrest-
      >oro-alimentary automatisms-->unilateral hand automatisms. All seizures with aura
      and including two or more symptoms of the clinical sequence (65%) were associated
      with a 1a, 1b, 2a or 2b EEG pattern. CONCLUSIONS: The identification of a
      specific clinical-EEG pattern provides a useful tool for the epileptogenic zone
      localization in non-invasive pre-surgical assessment of patients with hippocampal
      sclerosis. SIGNIFICANCE: The identification of a specific clinical-EEG pattern
      associated to neuroimaging findings and neuropsychological testing allows
      indicating surgery for the treatment of epilepsy in patients with hippocampal
      sclerosis, without performing any further complementary studies.

PMID- 14652089
TI  - Quantitative spectral analysis of EEG in psychiatry revisited: drawing signs out
      of numbers in a clinical setting.
AB  - OBJECTIVE: To evaluate the incidence, sensitivity and specificity of abnormal
      quantitative EEG (QEEG) measures in normal subjects and patients with mental
      disorders. METHODS: Normalized QEEG measures were blindly assessed in 67 normal
      human beings and 340 psychiatric patients. QEEG results were correlated to
      subject condition or diagnosis and magnetic resonance imaging (MRI) findings.
      RESULTS: QEEG was abnormal in 83% of patients, and 12% of normal subjects. The
      most frequent abnormality was a decrease in slow (delta and/or theta) bands,
      either alone, with beta increase, or with alpha decrease, followed by increase in
      beta band. No normal subject showed delta and/or theta decrease. Slow band
      decrease was more frequent in depression and mental disorders due to general
      medical condition, alcohol and drug dependence. However, no pattern was specific
      of any entity, and patients within the same diagnostic may present different
      patterns. Delta-theta decrease was correlated with cortical atrophy as seen in
      MRI. Beta increase was correlated with psychoactive medication. No association
      was found between any other QEEG pattern and MRI abnormalities, or medication.
      CONCLUSIONS: Decrease in the delta and theta bands of the QEEG can be regarded as
      a specific sign of brain dysfunction, and is correlated with cortical atrophy.
      However, this sign, as other QEEG abnormal patterns, can be found in many
      different disorders and none of them can be considered as pathognomonic of any
      specific disorder. SIGNIFICANCE: This work attempted to circumvent the alleged
      lack of Class I evidence of QEEG utility in the study of psychiatric patients by
      means of a prospective, blinded study, searching for specific signs of
      physiopathology in individual patients.

PMID- 14652090
TI  - Optimizing PCA methodology for ERP component identification and measurement:
      theoretical rationale and empirical evaluation.
AB  - OBJECTIVE: To determine how specific methodological choices affect "data-driven"
      simplifications of event-related potentials (ERPs) using principal components
      analysis (PCA). The usefulness of the extracted component measures can be
      evaluated by knowledge about the variance distribution of ERPs, which are
      characterized by the removal of baseline activity. The variance should be small
      before and at stimulus onset (across and within cases), but large near the end of
      the recording epoch and at ERP component peaks. These characteristics are
      preserved with a covariance matrix, but lost with a correlation matrix, which
      assigns equal weights to each sample point, yielding the possibility that small
      but systematic variations may form a factor. METHODS: Varimax-rotated PCAs were
      performed on simulated and real ERPs, systematically varying extraction criteria
      (number of factors) and method (correlation/covariance matrix, using
      unstandardized/standardized loadings before rotation). RESULTS: Conservative
      extraction criteria changed the morphology of some components considerably, which
      had severe implications for inferential statistics. Solutions converged and
      stabilized with more liberal criteria. Interpretability (more distinctive
      component waveforms with narrow and unambiguous loading peaks) and statistical
      conclusions (greater effect stability across extraction criteria) were best for
      unstandardized covariance-based solutions. In contrast, all standardized
      covariance- and correlation-based solutions included "high-variance" factors
      during the baseline, confirming findings for simulated data. CONCLUSIONS:
      Unrestricted, unstandardized covariance-based PCA solutions optimize ERP
      component identification and measurement.

PMID- 14652091
TI  - Abnormal warm and cold sensation thresholds suggestive of small-fibre neuropathy
      in sarcoidosis.
AB  - OBJECTIVE: A substantial number of sarcoidosis patients report apparently non
      specific symptoms such as pain, for which no organic substrate has yet been
      found. Recently we observed symptoms suggestive of small-fibre neuropathy in a
      group of sarcoidosis patients. The aim of the present study was to verify this
      observation using various electrophysiological tests. METHODS: In 74 sarcoidosis
      patients complaining of symptoms suggestive of small-fibre neuropathy, thresholds
      for warm (WS) and cold sensation (CS) as well as for heat pain were determined at
      the thenar eminence and the foot dorsum. Furthermore, sympathetic skin responses
      (SSR), nerve conduction studies and concentric needle electromyography were
      performed. In 31 patients, cardiovascular autonomic testing was carried out.
      RESULTS: Thermal threshold testing (TTT) revealed abnormalities in 51 of the 74
      patients. Abnormalities showed an asymmetrical distribution. WS was affected more
      often than CS and feet more often than hands. Nerve conduction studies in the
      legs showed slightly abnormal results in 6 patients; all of these had abnormal
      TTT results. The SSR was absent at the foot in 7 patients. Cardiovascular
      autonomic testing was abnormal in only a single patient. CONCLUSIONS: In a
      subgroup of sarcoidosis patients we found TTT abnormalities suggestive of small
      fibre neuropathy. SSR and cardiovascular autonomic testing appeared to be of
      little diagnostic value. Small-fibre neuropathy may be the cause of a number of
      hitherto unexplained symptoms in sarcoidosis.

PMID- 14652092
TI  - Marinacci communication: an electrophysiological study.
AB  - OBJECTIVE: Prevalence of Martin-Gruber anastomosis, an anomalous median-to-ulnar
      forearm communication, is well reported in literature while Marinacci
      communication, the reverse of Martin-Gruber with a forearm ulnar-to-median
      communication is under-recognized. We systematically evaluated the presence of
      Marinacci communication in a series of patients referred for electrophysiological
      studies. METHODS: One hundred consecutive patients referred to the
      electrophysiological laboratory for various diagnoses were studied using standard
      techniques for motor, sensory and f wave studies. RESULTS: Of the 100 patients
      (200 arms) studied, electrophysiological features of Marinacci communication were
      observed in 4 patients (7 arms). Median stimulation with recording over abductor
      pollicis brevis (APB) revealed a pseudo-conduction block over the forearm segment
      while on ulnar stimulation and recording over abductor digiti minimi (ADM), the
      amplitude of the compound muscle action potential (CMAP) obtained on proximal
      stimulation was higher than that obtained on distal stimulation. Ulnar
      stimulation at the elbow but not at the wrist revealed CMAP from APB without
      initial positivity. Its amplitude was 50% of the amplitude obtained on median
      stimulation at the wrist. CONCLUSIONS: Marinacci communication is not uncommon in
      the general population. A pseudo-conduction block on median stimulation and
      higher CMAP amplitude on proximal than distal stimulation provide valuable clues
      to its recognition.

PMID- 14652093
TI  - Selective spatial information from surface EMG after temporal filtering: the
      application to interference EMG using cross-covariance analysis.
AB  - OBJECTIVE: An increased spatial resolution in multichannel surface EMG recordings
      would provide new possibilities for the investigation of intermuscular and
      intramuscular coordination. A known analytical solution for volume conduction
      allows the conclusion that a high pass filtered surface electromyography (SEMG)
      signal contains information from a smaller environment near the recording
      electrode and therefore provides a higher spatial resolution. METHODS: The
      present paper concerns experiments on 9 subjects to measure, from the human
      biceps brachii muscle during static isometric contraction, using multichannel
      surface EMG. Cross-correlation functions between bipolar SEMG channels were
      calculated and high pass filtered. RESULTS: The correlation peaks showed the
      signs of propagating action potentials. The spatial width in the direction
      perpendicular to the muscle fibres decreased with increasing cut-off frequency.
      There exists an optimal cut-off frequency, which provides the best spatial
      resolution. It correlates with the thickness of the subcutaneous fat layer which
      causes a minimum depth of the active muscle fibres measured. CONCLUSIONS: High
      pass filtered cross-covariance functions of bipolar SEMG channels have an
      increased spatial resolution perpendicular to the muscle fibre direction and the
      frequency content of the signals can potentially give an indication of the depth
      of the active muscle fibres.

PMID- 14652094
TI  - A rare form of painful nondystrophic myotonia.
AB  - OBJECTIVE: In this paper we report a painful nondystrophic myotonia which has not
      been previously described. Pain is a rare symptom in myotonia. We report a
      myotonic disorder in a 34-year-old woman and her 14-year-old daughter. Painful
      cramps occur during and after exercise in the mother, and both patients can
      demonstrate unusual contractions in the tongue. In the present study we try to
      evaluate the mechanisms behind the unique finding of trains of high amplitude of
      positive waves, not seen in the earlier known myotonic conditions. METHODS:
      Clinical investigations and electromyography with single and dual channel
      recordings and muscle morphometry were performed. RESULTS: The electromyographic
      recordings reveal positive waves, fibrillation potentials and myotonic
      discharges. In addition, extraordinary findings were made of trains of high
      frequency positive potentials with very high amplitudes and with conduction block
      along the muscle fibres. CONCLUSIONS: In this new form of myotonia with likely
      dominant heredity, the specific finding of trains of high amplitude positive
      waves indicates ephaptic transmission within bundles of neighbouring muscle
      fibres.

PMID- 14652095
TI  - Reliability of electromyographic and torque measures during isometric axial
      rotation exertions of the trunk.
AB  - OBJECTIVE: The aim of the present study was to investigate the between-days
      reliability of electromyographic (EMG) measurement of 6 bilateral trunk muscles
      and also the torque output in 3 planes during isometric right and left axial
      rotation at different exertion levels. METHODS: Ten healthy subjects performed
      isometric right and left axial rotation at 100, 70, 50 and 30% maximum voluntary
      contractions in two testing sessions at least 7 days apart. EMG amplitude and
      frequency analyses of the recorded surface EMG signals were performed for rectus
      abdominis, external oblique, internal oblique, latissimus dorsi, iliocostalis
      lumborum and multifidus bilaterally. The primary torque in the transverse plane
      and the coupling torques in sagittal and coronal planes were measured. RESULTS:
      For both EMG amplitude and frequency values, good (intraclass correlation
      coefficient, ICC=0.75-0.89) to excellent (ICC>/=0.90) reliability was found in
      the 6 trunk muscles at different exertion levels during axial rotation. The
      reliability of both maximal isometric axial rotation torque and coupling torques
      in sagittal and coronal planes were found to be excellent (ICC>/=0.93).
      CONCLUSIONS: Good to excellent reliability of EMG measures of trunk muscles and
      torque measurements during isometric axial rotation was demonstrated. This
      provides further confidence of using EMG and triaxial torque assessment as
      outcome measures in rehabilitation and in the evaluation of the human performance
      in the work place.

PMID- 14652096
TI  - The variability of intracortical inhibition and facilitation.
AB  - OBJECTIVE: To assess the variability of transcranial magnetic stimulation paired
      pulse measurements of cortical excitability between subjects, between sessions
      and within subjects within sessions. METHODS: In experiment 1, intracortical
      inhibition and facilitation were assessed with a fixed conditioning stimulus
      intensity (CSI) of 80% of active motor threshold (AMT) whereas in experiment 2,
      the effect of different CSIs (60-110% of AMT) was investigated. RESULTS:
      Experiment 1 revealed that subjects differed significantly in the degree of
      inhibition and facilitation. Between sessions the variability was substantial as
      predicted by high within session variability. Experiment 2 allowed determination
      of individual thresholds for inhibition and facilitation. These thresholds were
      the best predictor of the amount of inhibition or facilitation at a given CSI.
      Across subjects we observed a high correlation of the threshold for inhibition
      (expressed in terms of maximum stimulator output) with AMT (r=0.93). Results for
      facilitation were more variable. CONCLUSIONS: The variability was high if a
      single CSI was used to compare the percent intracortical inhibition or
      facilitation between subjects, or between sessions. Much less variable was the
      threshold for intracortical inhibition/facilitation, which was highly correlated
      to AMT. We suggest that the ratio of CSI:AMT is a robust and useful additional
      measure of the integrity of neuronal circuits underlying intracortical
      inhibition/facilitation.

PMID- 14652097
TI  - Facilitation of motor evoked potentials in ischemic stroke patients: prognostic
      value and neurophysiologic correlations.
AB  - OBJECTIVE: To investigate the predictive value of paired transcranial magnetic
      stimulation (TMS) at rest in stroke patients in comparison with the predictive
      value derived from data obtained by single TMS during facilitation. METHODS:
      Fifty-six patients with a single ischemic lesion and no electromyographic
      responses from single TMS in the resting affected hand muscles participated in
      the study. TMS assessment was performed 32 days post-stroke. It consisted of a
      single stimulation at maximal output during facilitation (controlateral hand grip
      and elbow flexion) and a paired-pulse stimulation at rest with two stimuli at
      maximal output at interstimulus intervals ranging from 15 to 100 ms. Two blind
      clinical assessments using the 'motricity index' were carried out 26 and 76 days
      post-stroke. RESULTS: Thirty-seven percent of patients were responsive to single
      TMS during facilitation, had better clinical scores at both evaluations and
      better clinical recovery. Fifty-four percent of patients responded to paired TMS,
      had better clinical scores at the second evaluation and better clinical recovery.
      All patients who responded to the single stimulation paradigm also responded to
      the paired one. CONCLUSIONS: A positive correlation was found between the
      responsiveness to both the TMS paradigms (facilitation procedure and paired
      stimulation) and clinical recovery. This underlines the importance of
      facilitation during single TMS in stroke patients and suggests that paired TMS at
      rest might supplement this procedure in stroke studies.

PMID- 14652098
TI  - The influence of time preparation on motor processes assessed by surface
      Laplacian estimation.
AB  - OBJECTIVE: The present study was aimed at testing whether foreperiod duration
      affects the activity recorded over the primary sensorimotor cortices during the
      reaction time. METHODS: The foreperiod duration (500 or 2500 ms) was varied
      across blocks of trials during a between-hand choice reaction time task; surface
      Laplacians were estimated from EEG recordings by the source derivation method.
      RESULTS: Reaction time was shorter for the 500 ms foreperiod than for the 2500 ms
      foreperiod. A contralateral negativity/ipsilateral positivity pattern showed up
      over the primary sensorimotor cortices. The time between the contralateral
      negativity onset and the electromyographic onset was shorter for the 500 ms
      foreperiod than for the 2500 ms foreperiod, which suggests that the foreperiod
      affects the implementation of the motor command. Furthermore, the interval
      between the onset of the voluntary electromyographic activity and the mechanical
      response was shorter for the 500 ms foreperiod than for the 2500 ms foreperiod.
      CONCLUSIONS: These results indicate that time preparation affects both central
      and peripheral motor processes.

PMID- 14652099
TI  - EMG remains fractionated in Parkinson's disease, despite practice-related
      improvements in performance.
AB  - OBJECTIVE: We studied the ability of patients with Parkinson's disease to improve
      their performance in a motor task requiring both speed and accuracy in the
      execution of elbow flexion movements. Our goal was to investigate the changes in
      electromyographic activity associated with the changes in movement performance.
      METHODS: Eleven patients on anti-Parkinsonian medication were tested. The
      patients were selected for being bradykinetic, having little or no resting tremor
      or dyskinesias, and being in stages II or III of the Hoehn and Yahr rating scale.
      RESULTS: The untrained patients displayed multiple bursts of agonist activity,
      characteristic of Parkinsonian EMG recordings. All patients improved their
      performance by increasing peak velocity while maintaining movement accuracy
      within strict boundaries. With practice, the patients' performance changed in a
      manner similar to that which has been previously observed for performance curves
      in neurologically normal subjects. As movement duration decreased (i.e. peak
      velocity increased), we observed a slight decrease in the number of agonist
      bursts and an increase in the average burst duration. However, the patients
      continued to generate a fractionated, multi-burst agonist pattern. CONCLUSIONS:
      We conclude that Parkinsonian patients benefit from practice by improving their
      performance but remain fundamentally impaired in the generation of muscle
      activation patterns. This study has shown that the generation of fractionated,
      multiple short bursts of EMG activity that is characteristic of movements made by
      Parkinsonian patients is not normalized by practice.

PMID- 14652100
TI  - Decreased cortical excitability during motor imagery after disuse of an upper
      limb in humans.
AB  - OBJECTIVE: The present study investigated the effect of joint immobilization on
      corticomotoneuronal excitability to only intracortical input from a hierarchical
      level above the primary motor cortex. METHODS: Motor evoked potentials (MEPs) and
      H-reflexes in the flexor carpi radialis muscle were elicited from 8 orthopedic
      patients with splints and 8 healthy volunteers. Each patient was examined on the
      day of splint removal (disuse stage) and 2 months after that day (recovery
      stage). Both potentials were recorded under 3 conditions: at rest, while
      imagining motor movement (during motor imagery), and during 10% of maximum
      voluntary contraction (10% MVC). RESULTS: In the patient group, the amplitude of
      surface electromyography during voluntary maximum wrist flexion was lower at the
      disuse stage than at the recovery stage, although the supra-maximum M-wave
      amplitude did not change between stages. Compared to both the patient group at
      the recovery stage and the control group, patients at the disuse stage recorded
      significantly lower MEPs, but only during motor imagery. In contrast, the H
      reflex amplitudes were not significantly changed under any of the 3 conditions
      for both patients and control. CONCLUSIONS: The present results indicated a
      strict parallelism between motor execution (the reduction of electromyography
      during mvc after immobilization) and motor imagery (the reduction of MEP-amps
      after immobilization). This parallelism suggests that a functional reorganization
      or decreased excitability in the cerebral cortex area involved in executing
      movement likely decreases the motor capability to produce voluntary muscular
      output after immobilization.

PMID- 14652101
TI  - Motor representation in patients rapidly recovering after stroke: a functional
      magnetic resonance imaging and transcranial magnetic stimulation study.
AB  - OBJECTIVE: Neuroimaging studies have suggested an evolution of the brain
      activation pattern in the course of motor recovery after stroke. Initially poor
      motor performance is correlated with an recruitment of the uninjured hemisphere
      that continuously vanished until a nearly normal (contralateral) activation
      pattern is achieved and motor performance is good. Here we were interested in the
      early brain activation pattern in patients who showed a good and rapid recovery
      after stroke. METHODS: Ten patients with first-ever ischemic stroke affecting
      motor areas had to perform self-paced simple or more complex movements with the
      affected or the unaffected hand during functional magnetic resonance imaging
      (fMRI). The location and number of activated voxels above threshold were
      determined. To study possible changes in the cortical motor output map the
      amplitude of the motor evoked potentials (MEP) and the extent of the excitable
      area were determined using transcranial magnetic stimulation (TMS). RESULTS: The
      pattern of activation observed with movements of the affected and the unaffected
      hand was similar. In the simple motor task significant (P<0.05) increases were
      found in the primary motor cortex ipsilateral to the movement, the supplementary
      motor area and the cerebellar hemisphere contralateral to the movement during
      performance with the affected hand compared to movements with the unaffected
      hand. When comparing simple with more complex movements performed with either the
      affected or the unaffected hand, a further tendency to increased activation in
      motor areas was observed. The amplitude of MEPs obtained from the affected
      hemisphere was smaller and the extent of cortical output maps was decreased
      compared to the unaffected hemisphere; but none of the patients showed MEPs at
      the affected hand when the ipsilateral unaffected motor cortex was stimulated.
      CONCLUSIONS: Despite a rapid and nearly complete motor recovery the brain
      activation pattern was associated with increased activity in (bilateral) motor
      areas as revealed with fMRI. TMS revealed impaired motor output properties, but
      failed to demonstrate ipsilateral motor pathways. Successful recovery in our
      patients may therefore rely on the increased bilateral activation of existing
      motor networks spared by the injury.

PMID- 14652102
TI  - Depressed intracortical inhibition after long trains of subthreshold repetitive
      magnetic stimuli at low frequency.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) modulates cortical
      excitability. These effects outlast the rTMS train, and range from inhibition to
      facilitation according to the variables used for rTMS. Several studies have
      demonstrated short and long-term effects on motor evoked potential (MEP) size,
      whereas the effects on intracortical inhibition (ICI) and facilitation (ICF) are
      still unclear. We investigated short- (1-15 min), intermediate- (16-30 min), and
      long-term (6 h) effects on intracortical excitability. METHODS: Fourteen healthy
      subjects were stimulated with rTMS trains of 900 pulses (1 Hz, 90% resting motor
      threshold (rMTh)), delivered over the primary motor cortex and the occipital
      area. MTh, MEP size, silent period, intracortical inhibition at short (ICI) and
      long inter-stimulus intervals, and ICF were tested before and after rTMS.
      RESULTS: ICI was reduced 16-30 min after 1 Hz rTMS trains over the primary motor
      area, whereas the other response variables remained unchanged. The ICI reduction
      at 16-30 min was reproducible on different days in the same subjects; it was
      absent at 6 h and after stimulation of the occipital area. CONCLUSIONS:
      Subthreshold 1 Hz rTMS decreases ICI by reducing the excitability of
      intracortical inhibitory interneurones or by altering the electrical properties
      of the facilitatory chain of neurons responsible for the I waves.

PMID- 14652103
TI  - Motor preparation is more impaired in Parkinson's disease when sensorimotor
      integration is involved.
AB  - OBJECTIVE: This study aimed to investigate changes in spatio-temporal, event
      related (de)synchronization (ERD/ERS) patterns recorded with respect to the more
      akinetic versus the less akinetic side during performance of a visuo-guided
      targeting movement when compared to an index finger extension. METHODS: Twelve de
      novo parkinsonian patients were recorded. ERD/ERS in mu and beta frequency bands
      was computed from 21 source derivations. RESULTS: When the index finger extension
      was performed with the less akinetic limb, mu ERD focused over contralateral
      central region appeared 2 s before movement. With the targeting movement,
      additional pre-movement mu ERD was observed over the parietal region, as well as
      earlier ipsilateral mu ERD. When the same movements were performed with the more
      akinetic limb, we observed delayed mu ERD over contralateral regions, earlier
      ipsilateral mu ERD and a lack of contralateral parietal mu ERD before the
      targeting movement. Following index finger extension for the less akinetic limb,
      a focused contralateral central beta ERS was recorded, increasing and spreading
      after the targeting movement. In contrast, for the more akinetic limb, beta ERS
      was dramatically attenuated and remained unchanged after the targeting movement.
      CONCLUSIONS: These results confirm the fact that motor programming is delayed,
      and provide some insight into what may well be impaired sensorimotor integration
      in Parkinson's disease.

PMID- 14652105
TI  - Cortical and subcortical distribution of middle and long latency auditory and
      visual evoked potentials in a cognitive (CNV) paradigm.
AB  - OBJECTIVE: This study concerned sensory processing (post-stimulus late evoked
      potential components) in different parts of the human brain as related to a motor
      task (hand movement) in a cognitive paradigm (Contingent Negative Variation). The
      focus of the study was on the time and space distribution of middle and late post
      stimulus evoked potential (EP) components, and on the processing of sensory
      information in the subcortical-cortical networks. METHODS:
      Stereoelectroencephalography (SEEG) recordings of the contingent negative
      variation (CNV) in an audio-visual paradigm with a motor task were taken from 30
      patients (27 patients with drug-resistant epilepsy; 3 patients with chronic
      thalamic pain). The intracerebral recordings were taken from 337 cortical sites
      (primary sensorimotor area (SM1); supplementary motor area (SMA); the cingulate
      gyrus; the orbitofrontal, premotor and dorsolateral prefrontal cortices; the
      temporal cortex, including the amygdalohippocampal complex; the parietooccipital
      lobes; and the insula) and from subcortical structures (the basal ganglia and the
      posterior thalamus). The concurrent scalp recordings were obtained from 3
      patients in the thalamic group. In 4 patients in the epilepsy group, scalp
      recordings were taken separately from the SEEG procedure. The middle and long
      latency evoked potentials following an auditory warning (S1) and a visual
      imperative (S2) stimuli were analyzed. The occurrences of EPs were studied in two
      time windows (200-300 ms; and over 300 ms) following S1 and S2. RESULTS:
      Following S1, a high frequency of EP with latencies over 200 ms was observed in
      the primary sensorimotor area, the supplementary motor area, the premotor cortex,
      the orbitofrontal cortex, the cingulate gyrus, some parts of the temporal lobe,
      the basal ganglia, the insula, and the posterior thalamus. Following S2, a high
      frequency of EP in both of the time windows over 200 ms was observed in the SM1,
      the SMA, the premotor and dorsolateral prefrontal cortex, the orbitofrontal
      cortex, the cingulate gyrus, the basal ganglia, the posterior thalamus, and in
      some parts of the temporal cortex. The concurrent scalp recordings in the
      thalamic group of patients twice revealed potentials peaking approximately at 215
      ms following S1. Following S2, EP occurred with latencies of 215 and 310 ms,
      respectively. Following S1, separate scalp recordings in 4 patients in the
      epilepsy group displayed EP 3 times in the 'over 300 ms' time window. Following
      S2, EP were presented once in the '200-300 ms' time window and 3 times in the
      'over 300 ms' time window. CONCLUSIONS: The SM1, the SMA, multiple sites of the
      frontal lobe, some parts of the temporal lobe, the cingulate gyrus, the basal
      ganglia, the insula, and the posterior thalamus all participate in a cortico
      subcortical network that is important for the parallel cognitive processing of
      sensory information in a movement related task.

PMID- 14652104
TI  - Plasticity of the human motor system following muscle reconstruction: a magnetic
      stimulation and functional magnetic resonance imaging study.
AB  - OBJECTIVE: Although motor system plasticity in response to neuromuscular injury
      has been documented, few studies have examined recovered and functioning muscles
      in the human. We examined brain changes in a group of patients who had a muscle
      transfer. METHODS: Transcranial magnetic stimulation (TMS) was used to study a
      unique group of 9 patients who had upper extremity motor function restored using
      microneurovascular transfer of the gracilis muscle. The findings from the
      reconstructed muscle were compared to the homologous muscle of the intact arm.
      One patient was also studied with functional magnetic resonance imaging (fMRI).
      RESULTS: TMS showed that the motor threshold and short interval intracortical
      inhibition was reduced on the transplanted side while at rest but not during
      muscle activation. The difference in motor threshold decreased with the time
      since surgery. TMS mapping showed no significant difference in the location and
      size of the representation of the reconstructed muscle in the motor cortex
      compared to the intact side. In one patient with reconstructed biceps muscle
      innervated by the intercostal nerves, both TMS mapping and fMRI showed that the
      upper limb area rather than the trunk area of the motor cortex controlled the
      reconstructed muscle. CONCLUSIONS: Plasticity occurs in cortical areas projecting
      to functionally relevant muscles. Changes in the neuronal level are not
      necessarily accompanied by changes in motor representation. Brain reorganization
      may involve multiple processes mediated by different mechanisms and continues to
      evolve long after the initial injury. SIGNIFICANCE: Central nervous system
      plasticity following neuromuscular injury may have functional relevance.

PMID- 14652106
TI  - Event-related potential N270, a negative component to identification of
      conflicting information following memory retrieval.
AB  - OBJECTIVE: N270, an endogenous ERP component of conflict effect, was evoked in
      previous studies with S1-S2 paradigm. The present experiment is designed to
      confirm the speculation that this conflict-related negativity could also be
      elicited by stimulus probes having conflict with a memorized item in a visual
      post-retrieval comparison task. METHODS: A Sternberg probe-matching paradigm was
      modified in the present study. The stimuli consisted of a memory set of 3
      different items (simple figures) and a retrieval set of 3 probe figures. Subjects
      matched each probe to its corresponding item in the memory set. The tasks were
      designed with different conflict loads of no-conflict, low-conflict and high
      conflict in the probe retrieval test. RESULTS: Probes of no-conflict elicited a
      major positive going component, P300, with bilateral parietal distribution.
      Probes of low- and high-conflict evoked N270, while N430 was elicited only in
      high-conflict condition. N270 was more negative in high-conflict condition than
      in low-conflict condition. The N270 was right hemispheric prominent in the low
      conflict task and remarkably distributed over the right prefrontal areas. On the
      other hand, both N270 and N430 were distributed bilaterally on the scalp in the
      high-conflict task. CONCLUSIONS: The present results demonstrate that the N270 is
      an index to the conflict identification, while the N430 of the high-conflict task
      reflects the processing for complex conflicts following probe retrieval. These
      negativities are related to the processing of conflicts.

PMID- 14652107
TI  - N400 during lexical decision tasks: a current source localization study.
AB  - OBJECTIVE: Our primary aim in the present study was to establish the anatomic and
      psychophysiological correlates of automatic and controlled semantic priming.
      METHODS: Current sources were calculated on N400 component data from a previous
      study on lexical decision tasks [Clin Neurophysiol 1999;110:813] using the
      variable resolution electromagnetic tomography method (VARETA). In this study,
      two experiments were carried out, one using directly related pairs and the other
      one using mediated related pairs. Each experiment consisted of 3 tasks that
      required different levels of contribution from controlled processes. RESULTS:
      Average source localization images showed the brain structures involved in
      lexical decision tasks. The automatic component of the N400 effect was related to
      activation of occipitotemporal and parahippocampal gyri and anterior temporal
      lobes bilaterally. The expectancy strategy was related to activation of the right
      posterior temporal and right frontal areas. The postlexical strategy was
      associated with activation of right frontal, anterior cingulate and bilateral
      superior parietal areas. CONCLUSIONS: The findings indicated that the current
      sources of the N400 varied according to the relative contributions of automatic
      and controlled mechanisms. Moreover, the sources of the N400 effect depended on
      the type of strategy used.

PMID- 14652108
TI  - Development of a multi-channel exploratory battery for psychophysiological
      assessment: the Stress Profile.
AB  - OBJECTIVE: As the expanding field of psychophysiology is currently demanding
      applied methodologies to be used in the clinic, this study aimed to develop a
      practical multi-channel exploratory battery for psychophysiological evaluation of
      stress (the Psychophysiological Stress Profile; PSP). The PSP records 6
      psychophysiological variables and it is designed to be mainly used in the daily
      clinic. Moreover, the PSP was intended to be 'the method' to obtain normative and
      individual psychophysiological patterns, providing relevant information for the
      therapeutic process. METHODS: Two hundred and three subjects were evaluated with
      the PSP in two different contexts: the natural environment and the laboratory.
      Factorial analysis was applied to obtain psychophysiological profiles. These
      profiles are based on the covariation among different system responses. The Burt
      and Tucker Congruence Coefficient was used to compare factorial structures.
      RESULTS: A 3-factor structure was obtained in both contexts, Congruence
      Coefficient indicates that these factorial structures are very similar,
      indicating the existence of a unique and consistent psychophysiological pattern
      that characterizes the sample. CONCLUSIONS: The identified factorial structure
      shows relevant activation patterns, offering a comprehensive view of the
      subject's functioning. The structure is consistent through samples and can be
      considered as normative data for the studied population. PSP has turned out to be
      a quick and easy-to-use psychophysiological battery that has shown adequate
      internal consistency for all the recorded variables. In this way, the PSP
      methodology shows its practical value and usefulness in the assessment process.

PMID- 14652109
TI  - Failure of Digitimer's D-185 transcranial stimulator to deliver declared stimulus
      parameters.

PMID- 14652110
TI  - Nitrones as neuroprotective agents in cerebral ischemia, with particular
      reference to NXY-059.
AB  - Stroke is a major clinical problem, and acute pharmacological intervention with
      neuroprotective agents has so far been unsuccessful. Recently, there has been
      considerable interest in the potential therapeutic benefit of nitrone-derived
      free radical trapping agents as neuroprotective agents. Nitrone compounds have
      been shown to be beneficial in animal models of various diseases, and the
      prototypic compound alpha-phenyl-N-tert-butylnitrone (PBN) has been extensively
      demonstrated to be neuroprotective in rat models of transient and permanent focal
      ischemia. The nitrone radical trapping agent disodium 2,4-disulfophenyl-N-tert
      butylnitrone (NXY-059) has also been shown to be neuroprotective in these models.
      Furthermore, it has recently been shown to improve neurological function and
      reduce infarct volume in a primate model of permanent focal ischemia even when
      given 4 hr postocclusion. While radical trapping activity is demonstrable with
      NXY-059 and other nitrone compounds such as PBN, this activity is weak. Arguments
      for and against ascribing radical trapping as the therapeutic mechanism of action
      are discussed. This compound is well tolerated in human stroke patients and can
      be administered to produce plasma concentrations exceeding those effective in
      animal models; crucially, at the same time, it has also been shown to be
      effective in animal models. NXY-059 may thus be the first compound to be examined
      in stroke patients using drug exposure and time to treatment that have been shown
      to be effective in animal models of stroke.

PMID- 14652111
TI  - Vasodilating beta-adrenoceptor blockers as cardiovascular therapeutics.
AB  - beta-Adrenoceptor blocking agents (beta-blockers) have been established as
      therapeutics for treatment of patients with hypertension, ischemic heart
      diseases, chronic heart failure, arrhythmias, and glaucoma. However, their
      clinical use is limited because some patients are adversely affected by their
      side effects. The discovery of cardioselective (beta(1)-selective) blockers has
      overcome some of the problems. Current retrospective studies have revealed that
      vasodilating beta-blockers (so-called beta-blockers of the third generation) have
      advantages over the conventional type of beta-blockers in terms of minimizing the
      adverse effects and improving the disease-derived dysfunction, thus enhancing the
      quality of life variables. Some of the possible advantages include improvement of
      insulin resistance, decrease in low-density lipoprotein cholesterol in
      association with increase in high-density lipoprotein cholesterol, attenuation of
      bronchial asthma attack and respiratory dysfunction, alleviation of coronary
      vasospasm provocation, peripheral circulatory disturbances, and erectile
      dysfunction, and better patient compliance. Release of nitric oxide, antioxidant
      action, beta(2)-adrenoceptor activation, Ca(2+) entry blockade, and other
      mechanisms underlying the vasodilating action may be responsible for the
      beneficial therapeutic effects of these agents.

PMID- 14652112
TI  - Advances in nonhuman primate alcohol abuse and alcoholism research.
AB  - Advances in our understanding of the biological basis of alcohol abuse and
      alcoholism and the development of prevention and therapeutic intervention require
      appropriate animal models. Nonhuman primates are important to the study of
      complex biomedical disease processes. Genetic, anatomical, physiological, and
      behavioral similarities to humans offer unique opportunities for translational
      research along with the advantage of a degree of experimental control that is not
      possible in human studies. The purpose of this review is to outline the
      approaches taken with nonhuman primates as subjects in alcohol research and to
      highlight our current understanding of data on organismal variables that can be
      uniquely studied in these complex organisms. We review literature on alcohol self
      administration to provide an integrative framework for discussion of progress in
      2 important areas of research. Designs that incorporate self-administration
      provide a context for studying excessive alcohol consumption, including the
      organismal and environmental factors that influence risk for heavy drinking. We
      then review the use of monkeys to identify aspects of adverse biomedical
      consequences that follow excessive alcohol consumption. One of the primary
      conclusions to be drawn from this review is that nonhuman primates are a central
      part of the translational bridge in alcohol research, providing powerful and
      unique opportunities for experimental work that can address the biomedical
      complexities of alcohol abuse and alcoholism.

PMID- 14652113
TI  - Mechanisms involved in the induced differentiation of leukemia cells.
AB  - Despite the remarkable progress achieved in the treatment of leukemias over the
      last several years, many problems (multidrug resistance [MDR], cellular
      heterogeneity, heterogeneous molecular abnormalities, karyotypic instability, and
      lack of selective action of antineoplastic agents) still remain. The recent
      progress in tumor molecular biology has revealed that leukemias are likely to
      arise from disruption of differentiation of early hematopoietic progenitors that
      fail to give birth to cell lineage restricted phenotypes. Evidence supporting
      such mechanisms has been derived from studying bone marrow leukemiogenesis and
      analyzing differentiation of leukemic cell lines in culture that serve as models
      of erythroleukemic (murine erythroleukemia [MEL] and human leukemia [K562] cells)
      and myeloid (human promyelocytic leukemia [HL-60] cells) cell maturation. This
      paper reviews the current concepts of differentiation, the
      chemical/pharmacological inducing agents developed thus far, and the mechanisms
      involved in initiation of leukemic cell differentiation. Emphasis was given on
      commitment and the cell lineage transcriptional factors as key regulators of
      terminal differentiation as well as on membrane-mediated events and signaling
      pathways involved in hematopoietic cell differentiation. The developmental
      program of MEL cells was presented in considerable depth. It is quite remarkable
      that the erythrocytic maturation of these cells is orchestrated into specific
      subprograms and gene expression patterns, suggesting that leukemic cell
      differentiation represents a highly coordinated set of events that lead to
      irreversible growth arrest and expression of cell lineage restricted phenotypes.
      In MEL and other leukemic cells, differentiation appears to be accompanied by
      differentiation-dependent apoptosis (DDA), an event that can be exploited
      chemotherapeutically. The mechanisms by which the chemical inducers promote
      differentiation of leukemic cells have been discussed.

PMID- 14652114
TI  - Protein phosphatases that regulate multifunctional Ca2+/calmodulin-dependent
      protein kinases: from biochemistry to pharmacology.
AB  - Multifunctional Ca(2+)/calmodulin-dependent protein kinases (CaMKs) play pivotal
      roles in Ca(2+) signaling pathways, such as the regulation of the neuronal
      functions of learning, memory, and neuronal cell death. The activities of the
      kinases are strictly regulated by protein phosphorylation/dephosphorylation.
      Although the activation mechanisms for multifunctional CaMKs through
      phosphorylation, which correspond to "switch on," have been extensively studied,
      the negative regulatory mechanisms through dephosphorylation, which correspond to
      "switch off," have not. In this review, we focused on the regulation of
      multifunctional CaMKs by the protein phosphatases responsible. We first
      summarized the current understanding of negative regulation of CaMKs by known
      protein phosphatases and their physiological significance. We then discussed
      newly developed methods for detection of protein phosphatases involved in the
      regulation of CaMKs. We also summarized the biochemical properties of a novel
      protein phosphatase, which we isolated with the new methods and designated as
      CaMK phosphatase (CaMKP), and its homologue. Pharmacological implications for
      neuronal functions including memory and neuronal cell death are discussed from
      the viewpoint that regulation of protein kinase activity can be elucidated by
      focusing on protein phosphatases involved in its "switch off" mechanism.

PMID- 14652115
TI  - Fever and infection during parturition: a preanesthetic or a postanesthetic
      problem?

PMID- 14652116
TI  - Influence of form structure on the anesthesia preoperative evaluation.
AB  - STUDY OBJECTIVE: To determine the impact of changes in form design on the capture
      of administrative and clinical data elements. DESIGN: Randomized retrospective
      chart review. SETTING: Academic health center. PATIENTS: Patients undergoing
      surgical procedures in the operating rooms at Medical College Hospital.
      INTERVENTION: The principal intervention was the implementation of a newly
      designed anesthesiology preoperative evaluation form with the intent to improve
      data capture. MEASUREMENTS: Charts were reviewed for the presence or absence of
      the following indicators: Addressograph Stamp, Proposed Surgery, Current
      Medications, Medication Doses/Frequency, Allergies, ASA Physical Status,
      Anesthesia Plan, Attending Note, and fasting (NPO) Status. MAIN RESULTS:
      Completion of Proposed Surgery and ASA Physical Status was lower for the
      structured form. Completion of Attending Notes was higher with the new form.
      Medication Doses were more often completed, but they remained below desired
      levels on the new form. CONCLUSIONS: Design of a form can have a significant
      impact on the completion rate of form elements. Visual cues such as a labeled
      space for medication doses may improve the completion of these elements. Design
      layout can also have an influence on completion. In this case, changes to the
      layout may have impeded the completion rate for ASA Physical Status.

PMID- 14652117
TI  - Difficult airway management practice patterns among anesthesiologists practicing
      in the United States: have we made any progress?
AB  - STUDY OBJECTIVE: To determine the extent instruction and practice in the use of
      airway devices and techniques varies among anesthesiologists practicing in the
      United States. DESIGN: Survey questionnaire. SETTING: University medical center.
      MEASUREMENTS: Questionnaires were completed by American-trained anesthesiologists
      who attended the 1999 American Society of Anesthesiologists (ASA) Annual Meeting.
      Data collected included demographics, education, skills with airway
      devices/techniques, management of clinical difficult airway scenarios, and the
      use of the ASA Difficult Airway Algorithm. MAIN RESULTS: 1) DEMOGRAPHICS: 452
      questionnaires were correctly completed; 62% attending anesthesiologists, 70% <50
      years, 81% males, 44% from academic institutions, 63% >10 years of practice, 81%
      night duty, 77% board certified. 2) Education: 71% had at least one educational
      modality: difficult airway rotation, workshops, conferences, books, and
      simulators. 3) Skills: Miller blade 61%, Bullard laryngoscope 32%, LMA 86%,
      Combitube 43%, bougie 43%, exchangers 47%, cuffed oropharyngeal airway (COPA)
      34%, retrograde 41%, transtracheal needle jet ventilation 34%, cricothyrotomy
      21%, fiberoptics 59%, and blind nasal intubation 78%. The average reported use of
      special airway devices/techniques was 47.5%. 4) Management choices: failed
      intubation/ventilation: LMA (81%) and for all other situations: fiberoptic
      intubation. Use of ASA Difficult Airway Algorithm in clinical practice (86%).
      CONCLUSION: Fiberoptic intubation and the LMA are most popular in management of
      the difficult airway.

PMID- 14652118
TI  - Reduction of emetic symptoms during cesarean delivery with antiemetics: propofol
      at subhypnotic dose versus traditional antiemetics.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of propofol (at a
      subhypnotic dose), droperidol, and metoclopramide in reducing emetic symptoms
      during cesarean delivery. DESIGN: Randomized, double-blinded, placebo-controlled
      study. SETTING: University hospital. PATIENTS: 100 ASA physical status I and II
      parturients undergoing cesarean delivery with spinal anesthesia. INTERVENTIONS:
      Patients received placebo (saline) followed by placebo (Intralipid(R)), placebo
      (saline) followed by propofol at a subhypnotic dose (1.0 mg/kg/hr), droperidol
      1.25 mg followed by placebo (Intralipid(R)), or metoclopramide 10 mg followed by
      placebo (Intralipid(R)) intravenously (IV) immediately after clamping of the
      umbilical cord. MEASUREMENT AND MAIN RESULTS: The percentage of patients who were
      emesis-free, which was defined as experiencing no nausea, retching, or vomiting,
      in the intraoperative, postdelivery period was 80% with propofol, 80% with
      droperidol, and 78% with metoclopramide (p < 0.05), compared with placebo (40%).
      Severity of nausea was less inpatients who received propofol than in those who
      received placebo (p < 0.05), and there were no differences seen among the
      droperidol, metoclopramide, and placebo groups. No clinically serious adverse
      events as a result of the study drugs were observed in any of the groups.
      CONCLUSIONS: Prophylactic antiemetic efficacy of propofol at a subhypnotic dose
      (1.0 mg/kg/hr), droperidol 1.25 mg, and metoclopramide 10 mg is comparable in
      parturients undergoing cesarean delivery. Moreover, propofol at a subhypnotic
      dose is effective in the prevention of severe nausea.

PMID- 14652119
TI  - Standard Laryngeal Mask Airway and LMA-ProSeal during laparoscopic surgery.
AB  - STUDY OBJECTIVE: To compare the frequency of airway seal and sore throat with the
      LMA-ProSeal (PLMA) and the standard Laryngeal Mask Airway (LMA) during
      laparoscopic surgery. DESIGN: Prospective, controlled, randomized, nonblinded
      clinical study. SETTING: University-affiliated hospital. PATIENTS: 60 adult, ASA
      physical status I, II, and III patients undergoing laparoscopic surgery with
      general anesthesia, without contraindication to the use of the laryngeal mask.
      INTERVENTIONS: Patients were randomized to receive mechanical ventilation [tidal
      volume (V(T)) 7 mL/kg(-1); positive end-expiratory pressure (PEEP) 10 cmH(2)O]
      through the PLMA or the standard LMA, both equipped with a gastric tube.
      MEASUREMENTS: Heart rate, arterial pressure, inspiratory and expiratory V(T),
      airway pressure, end-tidal CO(2) partial pressure, and pulse oximetry were
      recorded. The leak fraction was calculated as the difference between the
      inspiratory and expiratory V(T) divided by the inspiratory V(T). Postoperative
      sore throat frequency was scored in the recovery room ("early") and 1 week after
      surgery ("late"). MAIN RESULTS: All patients were successfully ventilated through
      the assigned laryngeal mask. The leak fraction was 7 +/- 3% with the LMA and 7 +/
      4% with the PLMA (p = 0.731). In one patient, the PLMA drainage tube was not
      patent despite a leak fraction of 5%, and there was no clinically detectable air
      leak. During the recovery room stay, the frequency of sore throat was scored as
      mild in 13% and 10% of patients with the standard LMA and the PLMA, respectively,
      and was absent in the remaining patients (p = 0.99, between groups). There were
      no differences in the frequency of sore throat between the "early" and "late"
      evaluations (p = 0.99). CONCLUSIONS: The PLMA and the LMA show similar airtight
      efficiency during laparoscopy. The patency of the PLMA drainage tube should
      always be confirmed. The sore throat evaluation performed in recovery room
      appears as reliable as later evaluations.

PMID- 14652121
TI  - Myoclonus after prolonged infusion of etomidate treated with dantrolene.

PMID- 14652120
TI  - Comparison of general and spinal anesthesia and their influence on hemostatic
      markers in patients undergoing total hip arthroplasty.
AB  - STUDY OBJECTIVE: To evaluate the profile of molecular hemostatic markers in
      patients receiving either spinal or balanced general anesthesia for total hip
      arthroplasty. DESIGN: Open, randomized, observational study. SETTING: Orthopedic
      unit and central laboratory of a university hospital. PATIENTS: 26 consenting ASA
      physical status II and III inpatients undergoing total hip arthroplasty with
      general balanced anesthesia (n = 10) or spinal (regional) anesthesia (n = 16).
      INTERVENTIONS: The time course of seven procoagulatory and fibrinolytic
      parameters was examined during and after surgery in both groups of patients
      (general and regional). Blood samples were drawn on the day before surgery,
      directly before induction of general anesthesia or regional anesthesia,
      respectively, intraoperatively (before bone manipulation), at the end of surgery,
      and on the mornings of postoperative days 1 and 5. MEASUREMENTS AND MAIN RESULTS:
      The coagulation samples were centrifuged within 1 hour of collection at 2,300 g
      for 15 minutes at 4 degrees C. Hemoglobin, hematocrit, platelets, fibrinogen,
      prothrombin time, thrombin time, activated partial thromboplastin time,
      antithrombin, and protein C were measured immediately on arrival at the
      laboratory. Specimens were then aliquoted and stored at -70 degrees C. Within 2
      weeks, samples were thawed and prepared for the following assays: thrombin
      antithrombin complexes (TAT complexes), D-dimers, plasminogen activator inhibitor
      type 1 (PAI-1), and plasminogen and plasmin inhibitor. Maximum activation of
      coagulation was not reached until 2 hours postoperatively and then slowly
      decreased until normal values were reached around the fifth postoperative day.
      Parameters displaying the greatest changes were antithrombin and D-dimers. No
      statistically significant differences were found between the two groups at the
      individual time points. CONCLUSION: Our initial hypothesis that the lesser risk
      of postoperative DVT in patients undergoing total hip arthroplasty in regional
      anesthesia is reflected in the course of the plasmatic molecular markers of
      hemostasis could not be verified. There were no significant differences in the
      timely course of the markers at any given time point.

PMID- 14652122
TI  - Bedside exclusion of clinically significant recirculation volume during
      venovenous ECMO using conventional blood gas analyses.
AB  - STUDY OBJECTIVE: To investigate prospectively whether blood gas samples drawn
      from extracorporeal membrane oxygenation (ECMO) cannulae help to exclude at least
      clinically significant recirculation volumes in patients with acute respiratory
      failure. DESIGN: Feasibility study. SETTING: Intensive care unit at a university
      affiliated hospital. PATIENTS: Ten consecutive adult patients suffering from
      severe respiratory failure and undergoing ECMO. INTERVENTIONS: The drawing
      (venous) ECMO cannula was placed into the inferior vena cava via a femoral vein,
      and the oxygenated blood was returned via the right subclavian vein by
      supraclavicular access directly into the right atrium. Blood gas samples were
      obtained from both cannulae. MEASUREMENTS AND MAIN RESULTS: The median arterial
      oxygen tension (PaO(2)) obtained from the arterial cannula was 537 mmHg (range,
      366 to 625 mmHg), the median mixed venous oxygen tension (PvO(2)) drawn from the
      venous cannula was 42 mmHg (range, 25 to 54 mmHg), which was less than 10% of
      that observed in the arterial cannula, and also within the physiologic range of
      PvO(2). The ECMO flow necessary to maintain patients' oxygen saturation above 90%
      (4.1 L/min; range, 1.95 to 5.8 L/min) was significantly lower than the patients'
      cardiac output (CO; 6.2 L/min; range, 4.1 to 7.9 L/min; p < 0.001). CONSLUSIONS;
      We recommend obtaining blood gas samples-immediately after initiation of ECMO
      from both cannulae. A PvO(2) within physiologic range and below 10% of PaO(2)
      rules out any clinically relevant recirculation volume.

PMID- 14652123
TI  - Evaluation of intense neuromuscular blockade caused by rocuronium using
      posttetanic count in male and female patients.
AB  - STUDY OBJECTIVE: To establish the relationship between train-of-four (TOF) nerve
      stimulation and the number of posttetanic twitches (posttetanic count [PTC])
      during neuromuscular blockade caused by rocuronium in males and females. DESIGN:
      Prospective, observational, clinical comparison. SETTING: Operating room of a
      university hospital. PATIENTS: 60 ASA physical status I and II patients (30 women
      and 30 men), aged 18 to 60 years, who were scheduled for elective orthopedic
      surgery and ear, nose, throat surgery with a planned duration of 2 hours.
      INTERVENTIONS; During fentanyl, propofol, and nitrous oxide (N(2)O) anesthesia,
      neuromuscular blockade was evaluated with accelerometry of the thumb using TOF
      and posttetanic twitch stimulation (PTTS) of the ulnar nerve in patients who
      received rocuronium 1 mg.kg(-1). MEASUREMENTS AND MAIN RESULTS: The first
      responses to PTTS were seen at mean times of 34.9 and 37.7 minutes after
      rocuronium injection in male and female patients, respectively (NS). The average
      interval between the appearance of a posttetanic response and the first response
      to TOF stimulation (T1) was not significantly different between male and female
      patients (15.4 +/- 4.8 min (SD) vs. 15.9 +/- 4.9 min, respectively). There was a
      significant negative correlation between PTC and the time to first response to
      TOF nerve stimulation (r = -0.83; p = 0.0001). Gender did not have a
      statistically significant effect on this relation (F = 0.9; p = 0.34). The
      intervals from administration of rocuronium to the first appearances of T1 and T2
      were not significantly different between the two groups, but the intervals to the
      first appearances of T3 and T4 were significantly longer in female patients.
      CONCLUSIONS: Even though the times from initial administration of rocuronium 1
      mg.kg(-1) to the first appearances of T3 and T4 are significantly longer in
      female patients, the intervals to the first detectable responses to PTTS and TOF
      are not significantly different between females and males. Gender has no
      significant effect on the relation between PTC and the time to T1.

PMID- 14652124
TI  - Current understanding of the patient's attitude toward the anesthetist's role and
      practice in Israel: effect of the patient's experience.
AB  - STUDY OBJECTIVE: To assess the patient's understanding and knowledge of the
      anesthesiologist's role and responsibilities in the operating room and in other
      areas of hospital activity, and to delineate the effect of previous anesthetic
      experience on this knowledge. DESIGN: Prospective study consisting of standard
      preanesthetic interview and questionnaire survey. SETTING: Preoperative
      anesthetic clinic in a large central private hospital in Israel. PATIENTS: 295
      adult patients who were seen in the preanesthetic clinic in a 4-week period in
      May, 2000. INTERVENTIONS: After patients were checked for exclusion criteria and
      given a standard preanesthetic interview, all adult patients presenting to this
      clinic were asked to participate in the study and complete a questionnaire, which
      was later evaluated statistically. RESULTS: A total of 295 patients (90% response
      rate) took part in the study. Two hundred (67.8%) patients had previous
      experience with anesthetics (Group A), and 95 (32.2%) patients presented for the
      first time for anesthesia (Group B). Ninety-five percent in Group A and 94.7% of
      Group B believed that the anesthesiologist is a doctor. Ninety-three percent of
      Group A and 90.5% of Group B answered that the anesthesiologist himself
      administered the anesthetic drugs. As to the responsibility for the patient's
      well-being during the operation and postoperatively, opinion was divided equally
      as to whether the surgeon or the anesthesiologist is responsible. The patients in
      both groups seemed to be well informed about the way anesthetic drugs act. Only
      4% of patients of both groups knew about the anesthesiologist's other duties
      outside the operation room. CONCLUSION: If able to be extrapolated to all of
      Israel, our results show a high appreciation for the physician status of the
      anesthesia professional and role in safe recovery. Passive learning from a prior
      anesthetic experience did not appear to improve such appreciation.

PMID- 14652126
TI  - Effective use of the esophageal tracheal Combitube following severe burn injury.
AB  - We present the case of a patient status post previous burn injury, undergoing
      elective surgery in which the Combitube was used because contractural formation
      of the mouth and tracheal stenosis precluded tracheal intubation. The Combitube
      proved to be highly successful in this patient who had a very limited mouth
      opening.

PMID- 14652125
TI  - Postoperative confusion in schizophrenic patients is affected by interleukin-6.
AB  - STUDY OBJECTIVE: To investigate whether epidural analgesia with local anesthetics
      affects postoperative confusion in schizophrenic patients or the relationships
      between cortisol or interleukin-6 (IL-6) and postoperative confusion. DESIGN:
      Prospective, randomized study. SETTING: Hakodate Watanabe Hospital and Hirosaki
      National Hospital. PATIENTS: 105 patients who were scheduled to undergo abdominal
      surgery with general anesthesia. INTERVENTIONS: The schizophrenic patients were
      rendomly divided into two groups: patients in Group A received epidural
      anesthesia and patients in Group B did not receive epidural anesthesia.
      MEASUREMENTS AND MAIN RESULTS: Postoperative confusion during the first 48 hours
      after the end of operation occurred in 7 of 33 patients (21%) in Group A and 10
      of 33 patients (30%) in Group B. There were no significant differences in the
      frequency of postoperative confusion between Groups A and B. Plasma cortisol
      concentrations in schizophrenic patients in Group A were significantly lower 15
      minutes after incision and the end of surgery than those levels of patients in
      Group B; however, there was no significant difference between groups in plasma
      cortisol concentrations after anesthesia. Plasma IL-6 concentrations (51.7 +/-
      22.0 and 31.4 +/- 8.2 pg mL(-1)) in patients with postoperative confusion at the
      end of surgery and 24 hours after surgery were significantly higher than those
      levels (34.4 +/- 16.2 and 16.9 +/- 7.7 pg mL(-1)) in patients without
      postoperative confusion. CONCLUSIONS: Epidural anesthesia does not significantly
      decrease the frequency of postoperative confusion in schizophrenic patients.
      Plasma IL-6 concentrations at the end of the operation and 24 hours after surgery
      in schizophrenic patients with postoperative confusion were significantly higher
      than those concentrations in patients without postoperative confusion.

PMID- 14652127
TI  - A two-person technique for fiberscope-aided tracheal extubation/reintubation in
      intensive care unit (ICU) patients.
AB  - The technique of fiberoptic-aided intubation for management of a difficult airway
      is often limited in the presence of blood or secretions and conditions in which
      the passage of a fiberoptic bronchoscope ("fiberscope") beneath the epiglottis
      and into the glottic opening may prove difficult. Direct laryngoscopy can be
      utilized in combination with the fiberscope as a two-person technique to overcome
      these challenges. We report the usefulness of a two-person technique using the
      flexible fiberscope in combination with direct laryngoscopy for
      extubation/reintubation in two intensive care unit patients with known difficult
      airways.

PMID- 14652128
TI  - Unusual presentation and complication of the prone position for spinal surgery.
AB  - Patient positioning for operative procedures has long been associated with
      perioperative complications. We present a case report of shoulder dislocation,
      which occurred following positioning in the prone position, and was detected by
      axillary artery occlusion resulting in the loss of the radial artery blood
      pressure line waveform. We discuss the diagnosis and consequences of this
      complication.

PMID- 14652129
TI  - The epidural test dose in obstetric anesthesia: it is not obsolete.
AB  - Many anesthesiologists have called for the abandonment of the epidural test dose
      in the obstetric patient, citing its lack of sensitivity and specificity. A test
      dose of lidocaine 1.5% with epinephrine 1:200,000, in combination with
      aspiration, is highly effective in detecting incorrect placement of an epidural
      catheter. If the catheter is intrathecal, it requires approximately 2 minutes to
      obtain a sensory level. For the detection of an intravascular catheter, a
      positive test dose would result in a sudden increase in the maternal heart rate
      of 10 beats per minute within 1 minute after injection. It should not be
      administered during uterine contraction, as labor pain may trigger a tachycardic
      response. This test dose has been extensively studied and is safe both for both
      mother and fetus.

PMID- 14652130
TI  - Anesthetic management of the parturient with fever and infection.
AB  - Fever is a common clinical problem in labor and delivery suites. It can result
      from a variety of infectious microorganisms, tissue trauma, malignancy, drug
      administration, and endocrine and immunologic disorders. Infection is the most
      common cause of fever, reflecting the effect of pyrogens on the hypothalamus. The
      diagnosis of infection in pregnancy often raises questions about the safety of
      regional anesthesia in febrile patients. Despite this concern, and lack of
      universal guidelines, it has now been well established that the presence of
      infection and fever in labor does not always contraindicate the administration of
      regional anesthesia.

PMID- 14652131
TI  - Comment on "Perioperative interscalene blockade: an overview of its history and
      current clinical use".

PMID- 14652133
TI  - Cloning and characterization of the bovine class 1 and class 2 insulin-like
      growth factor-I mRNAs.
AB  - Insulin-like growth factor-I (IGF-I) is an important regulator of growth,
      development, and metabolism, and is the primary mediator of the growth-promoting
      activity of growth hormone (GH) in animals. In several species, the IGF-I
      polypeptide is generated from IGF-I mRNA containing either exon 1 (class 1 IGF-I
      mRNA) or exon 2 (class 2 IGF-I mRNA) as the leader exon. The objectives of this
      study were to identify class 1 and class 2 IGF-I mRNAs in cattle and to compare
      their expression in different tissues, their response to GH, and their
      translational efficiency. Three class 1 IGF-I cDNAs corresponding to three
      different transcription start sites in exon 1 and one class 2 IGF-I cDNA were
      identified from adult cattle liver using 5'-rapid amplification of cDNA ends (5'
      RACE). Both classes of IGF-I mRNAs were expressed in a variety of tissues, with
      the highest level in liver; class 1 IGF-I mRNA was more abundant than class 2 IGF
      I mRNA in all tissues. Six hours after a single intramuscular injection of 500 mg
      of recombinant bovine GH, class 1 and class 2 IGF-I mRNAs in steer liver were
      increased by 29% (P=0.07) and 62% (P<0.05), respectively. The luciferase reporter
      mRNA fused to a class 1 IGF-I 5'-untranslated region (5'-UTR) was translated four
      times more efficiently in vitro than the luciferase reporter mRNA fused to a
      class 2 IGF-I 5'-UTR (P<0.05). These results indicate that the IGF-I gene in
      cattle is transcribed as class 1 and class 2 IGF-I mRNAs and that the two classes
      of IGF-I mRNAs may be regulated differentially at both transcriptional and
      translational levels.

PMID- 14652134
TI  - Effects of endocrine disrupting compounds on the pathology and oestrogen receptor
      alpha and beta distribution in the uterus and cervix of ewe lambs.
AB  - A number of chemicals have been classed as endocrine disrupting compounds due to
      their ability to mimic the actions of endogenous hormones in vivo and in vitro.
      The objective of this experiment was to determine the pathological changes and
      oestrogen receptor (ER) distribution in the cervix and uterus of prepubertal
      ovariectomised ewe lambs following exposure to a range of compounds with a
      predominantly oestrogenic effect. Lambs were exposed to diethylstilbestrol (0.175
      mg/kg biweekly), bisphenol-A (3.5mg/kg biweekly) or octylphenol (3.5mg/kg
      biweekly) for 6 weeks. Following sacrifice, uterine and cervical tissue pathology
      was assessed. The endometrial and myometrial areas were quantified and the
      distribution of ERalpha and ERbeta assessed by immunohistochemistry. No
      differences were observed between control and octylphenol-exposed lambs in
      uterine gross pathology and histopathology. Uteri from bisphenol-A- and
      diethylstilbestrol-exposed lambs were heavier than both control and octylphenol
      exposed lambs. In the bisphenol-A-exposed lambs, endometrial oedema accounted for
      a significant increase in the endometrial cross-sectional area over the other
      groups. Uteri from animals exposed to diethylstilbestrol showed variable
      pathology including oedema and cellular proliferation. Keratinisation of the
      cervical epithelium was observed in both bisphenol-A- and diethylstilbestrol
      exposed lambs. Exposure to diethylstilbestrol and bisphenol-A was associated with
      a diffuse intracellular distribution of ERalpha and ERbeta in the uterine
      endometrium. This was in addition to the strong cytoplasmic staining of uterine
      epithelial cells and nuclear staining of specific sub-epithelial cells observed
      in all groups. We conclude that a 6-week exposure of lambs to bisphenol-A and
      diethylstilbestrol altered the uterocervical environment and has the potential to
      disrupt subsequent reproductive function. Pathological changes could not be
      detected in the uterus or cervix of lambs exposed to octylphenol.

PMID- 14652135
TI  - Evaluation of serum insulin-like growth factor binding proteins (IGFBP) in Angus
      cattle divergently selected for serum IGF-I concentration.
AB  - Postweaning serum insulin-like growth factor-I (IGF-I) concentrations and serum
      IGF binding proteins (IGFBP) were investigated in 68 (1992 Fall-born) and 84
      (1999 Fall-born) Angus cattle selected for either high or low serum IGF-I
      concentrations since 1989. Relative serum levels of IGFBP were determined by
      [125I]IGF-I Western ligand blotting. IGFBP species of 38-42, 34, 30, and 24 kDa
      were identified. The 34 kDa species was identified as IGFBP-2 by immunoblot
      analysis. No significant line effects were observed for any of the IGFBP. In both
      1992 and 1999, heifers had higher IGFBP-2 levels than bulls (P<0.0005). In 1992
      calves, relative levels of the 38-42 and 24 kDa species were significantly
      correlated with serum IGF-I concentration. In 1999 calves, none of the IGFBP were
      correlated with serum IGF-I, although IGFBP-2 was negatively correlated with
      several measures of body weight. No significant line effects were observed for
      growth or serum IGF-I traits in 1992 calves. However, 1999 high line calves had
      higher serum IGF-I concentrations and body weights than low line calves (P<0.05).
      In both 1992 and 1999 calves, bulls had higher serum IGF-I concentrations and
      body weights than heifers (P<0.05). Thus, while selection for high versus low
      serum IGF-I concentrations has resulted in divergence between the selection lines
      and also in changes in body weights, it has not resulted in changes in serum
      IGFBP levels. Furthermore, circulating IGFBP-2 appears to be higher in heifers
      than in bulls, and also appears to be negatively correlated with body weights.

PMID- 14652137
TI  - Sex differences in oestrogen receptor levels in adrenal glands of sheep during
      the breeding season.
AB  - The concentrations of the oestrogen receptor (ER), and the mRNA levels of
      ERalpha, progesterone receptor (PR) and insulin-like growth factor I (IGF-I) were
      characterised in adrenal glands and uterine tissue of adult Corriedale sheep
      during the breeding season. The sheep were of different sex and gonadal status.
      Ewes had higher levels of cytosolic ER in the adrenals than the rams (mean+/
      S.E.M.: 7.3+/-2.0 fmol/mg protein and 2.5+/-1.0 fmol/mg protein, respectively;
      P=0.0091) and gonadectomy increased ER (mean+/-S.E.M.: 2.9+/-1.2 fmol/mg protein
      and 8.6+/-2.3 fmol/mg protein, intact and gonadectomised sheep, respectively;
      P=0.0071). No differences could be observed in mRNA levels for ERalpha and IGF-I
      in the adrenal glands of all of the sheep. PR mRNA levels were reduced in
      ovariectomised ewes and enhanced in castrated rams (sex x gonadal status:
      P=0.009). PR mRNA levels tended to be higher in ewes in the follicular phase than
      in ovariectomised ewes and intact rams (P<0.1). All of the animals had positive
      nuclear staining for ERalpha in the adrenal cortex, but no differences were
      observed between the groups. In this study, we demonstrated the existence of ER
      in the adrenal gland of sheep and found varying sensitivity to oestrogens as the
      ER levels differed among sex and gonadal status. These findings indicate that
      oestrogens most likely affect steroidogenesis directly at the adrenal cortex and
      suggest that oestrogens are partly responsible for the sex differences in
      cortisol secretion in sheep.

PMID- 14652136
TI  - The mRNA expression of the members of the IGF-system in bovine corpus luteum
      during induced luteolysis.
AB  - The components of the IGF-system were shown to be differentially regulated in
      bovine antral follicles and corpora lutea (CL) during different stages of the
      estrous cycle, and to have important functions for specific stages. The aim of
      this study was to investigate the detailed pattern of mRNA expression of most
      constituents of the IGF-system and their possible involvement in prostaglandin
      (PG)F2alpha-induced luteolysis in the bovine CL. Therefore, cows in the mid
      luteal phase (days 8-12) were injected with the PGF2alpha-analogue Cloprostenol,
      and CL were collected by transvaginal ovariectomy at 2, 4, 12, 48 and 64 h after
      PGF2alpha-injection. Real-time RT-PCR using SYBR Green I detection was employed
      to determine mRNA expressions of the following factors: ubiquitin (UBQ), insulin
      like growth factor I (IGF I), IGF II, IGF-receptor type 1 (IGFR-1), growth
      hormone receptor (GH-R) and IGF-binding proteins-1-6 (IGFBP-1-6). Total
      extractable RNA decreased with ongoing luteolysis. IGFBP-1 mRNA was significantly
      up-regulated at 2h after PGF2alpha and maximal at 4h with a 34-fold increase.
      IGFBP-5 mRNA was significantly up-regulated after 12h with a maximum of an 11
      fold increase at 64 h. For GH-R, IGFR-1, IGF II, IGFBP-3 and -4 mRNA expression,
      we found a significant down-regulation in certain stages. There was a significant
      up-regulation for IGFBP-2 and -6 mRNA at 64 h after induced luteolysis. There
      were no significant changes in IGF I mRNA expression. In conclusion, the IGF
      system with all its components seems to play an important role in the very
      complex process of PGF2alpha-induced luteolysis in bovine CL.

PMID- 14652138
TI  - The chicken pituitary expresses an ovoinhibitor-like protein in subpopulations of
      some, but not all, hormone-producing cell types.
AB  - Ovoinhibitor is a serine protease-inhibiting protein that was originally purified
      from egg whites. It is secreted by the oviduct under the control of estrogen and
      progesterone and it specifically inhibits serine proteinases such as trypsin and
      chymotrypsin. During recent attempts to raise monoclonal antibodies (Mabs)
      against chicken bursa of Fabricius proteins, one Mab was produced that
      specifically recognized chicken ovoinhibitor. This was the first demonstration of
      ovoinhibitor in an avian immune organ. We presently report on the expression of
      an ovoinhibitor-like molecule by the pituitary of the chicken as revealed by
      immunocytochemistry and RT-PCR. Immunofluorescent dual staining experiments using
      the mouse anti-ovoinhibitor Mab in conjunction with polyclonal antibodies against
      various hypophysial hormones revealed partial co-localization of an ovoinhibitor
      like molecule with growth hormone (GH), luteinizing hormone (LH), and pro
      opiomelanocortin (POMC), in a subset of the respective hormone producing cells.
      By contrast, no co-localization with prolactin (PRL) could be reliably
      demonstrated. RT-PCR of hypophysial mRNA using ovoinhibitor gene-specific primers
      yielded an amplicon that was 20% shorter than predicted on the basis of the
      published ovoinhibitor sequence. Sequencing revealed that of the represented
      exons only the central portion was expressed in the pituitary and that both 5'
      and 3' ends of each exon had been truncated. While expression of ovalbumin-like
      serine protease inhibitors (serpins) has been previously reported in the rat
      pituitary, to our knowledge, this is the first report of a Kazal-type serine
      protease inhibitor in the vertebrate neuroendocrine system.

PMID- 14652139
TI  - MR contrast of ferritin and hemosiderin in the brain: comparison among gradient
      echo, conventional spin-echo and fast spin-echo sequences.
AB  - OBJECTIVE: To compare the magnetic resonance image contrasts due to ferritin and
      hemosiderin in the brain tissue among different pulse sequences. MATERIALS AND
      METHODS: Fourteen patients with cavernous hemangioma in the brain prospectively
      underwent MR imaging with T2*-weighted gradient-echo (GRE), T2-weighted
      conventional spin-echo (SE) and fast spin-echo (FSE) sequences. The relative
      contrast ratios (CRs) of the hypointense part of cavernous hemangioma, globus
      pallidus and putamen to the deep frontal white matter were measured on each pulse
      sequence and statistically analyzed using analysis of variance followed by paired
      t-test. RESULTS: In the hypointense part of cavernous hemangioma, relative CRs
      were significantly lower on T2*-weighted GRE than on T2-weighted SE images
      (P=0.0001), and on T2-weighted SE than on T2-weighted FSE images (P=0.0001). In
      the globus pallidus, relative CRs were significantly lower on T2-weighted SE than
      on T2*-weighted GRE images (P=0.002), and on T2*-weighted GRE than on T2-weighted
      FSE images (P=0.0002). In the putamen, relative CRs were significantly lower on
      T2-weighted SE than on T2*-weighted GRE images (P=0.001), and there was no
      significant difference between CRs on T2-weighted FSE and T2*-weighted GRE images
      (P=0.90). CONCLUSION: Hemosiderin showed best image contrast on T2*-weighted GRE
      images but ferritin showed more prominent image contrast on T2-weighted SE than
      on T2*-weighted GRE images, which may help to determine an appropriate pulse
      sequence in neurological diseases associated with excessive ferritin
      accumulation.

PMID- 14652140
TI  - 'The Closer'-percutaneous vascular suture device: evaluation of safety and
      performance in neuroangiography.
AB  - OBJECTIVE: To evaluate the use of the suture mediated vascular closure device
      concerning practicability and safety in clinical angiography practice. MATERIAL
      AND METHODS: One hundred and seventeen patients (59 female, 58 male, mean age
      40.9+/-13.4) underwent percutaneous closure of common femoral arterial puncture
      sites following diagnostic neuroangiography using the suture device 'the Closer'
      (Perclose Inc., Redwood City, CA, USA). Primary success, early problems (within
      24 h) and late complications were evaluated. Complications were graded as minor
      and severe with or without need of surgical intervention and categorized by type.
      Parameters such as age, gender, sheath size and number of previous arterial
      punctures were evaluated with respect to complications. RESULTS: Percutaneous
      closure was primary successful in 85% (100/117). The overall complication rate
      was 32% (28% mild n=35, 4% severe n=6, which needed surgical intervention). All
      but one problem occurred within the first 24 h after the suture. Additional
      manual compression was necessary in 32 cases (25%). There was no significant
      difference in age and gender between the groups with and without complications.
      Sheath size was significantly larger (P<0.01) and numbers of preceeding
      angiograms were significantly higher (P<0.01) in the complications group compared
      with uncomplicated cases. CONCLUSION: The evaluated percutaneous vascular suture
      device is useful in clinical practice but limitations concerning patient
      selection seem to emerge in order to avoid complications.

PMID- 14652141
TI  - Differentiation of cerebral tumors using multi-section echo planar MR perfusion
      imaging.
AB  - OBJECTIVE: We have investigated the performance of magnetic resonance (MR)
      perfusion imaging to differentiate between astrocytomas grade II, grade III and
      glioblastomas in a prospective study. MATERIALS AND METHODS: In 33 patients with
      suspected supratentorial primary cerebral tumors we performed multi-section Echo
      Planar MR perfusion imaging. Regional cerebral blood volume (rCBV) maps were
      calculated and the maximum rCBV was determined from the entire lesion. This value
      was divided by the mean rCBV value from the contralateral side, which provided
      the rCBV index used in this study. The rCBV index was correlated with the
      histological tumor classification after stereotactic biopsy (n=7) or open
      resection (n=26). RESULTS: The maximum rCBV index was 1.2+/-0.8 for grade II
      astrocytomas (n=3), 4.0+/-1.2 for grade III astrocytomas (n=13), and 10.3+/-3.3
      for glioblastomas (n=17). The difference between grade III astrocytomas and
      glioblastomas was highly significant (P<0.001). DISCUSSION AND CONCLUSION: The
      rCBV index measured with multi-section Echo Planar MR perfusion is capable of
      differentiating grade III astrocytomas from glioblastomas. It serves as an
      additional parameter to establish a diagnosis in cases where it is not possible
      to clearly differentiate between these types of tumors on the basis of
      conventional MR imaging. MR perfusion imaging also provides information about
      spatial heterogeneities within a tumor which might improve diagnostic
      performance. This technology may also be of interest for follow-up examinations
      after histological diagnosis and further treatment.

PMID- 14652142
TI  - Does ultrasound contrast agent improve the diagnostic value of colour and power
      Doppler sonography in superficial lymph node enlargement?
AB  - OBJECTIVE: to analyse whether ultrasound contrast agent (UCA) improves the
      diagnostic accuracy to differentiate between benign and malignant superficial
      lymph node enlargement by using colour-coded duplex sonography (CCDS) and power
      Doppler (PD). METHODS: 32 patients with suspected malignant superficial lymph
      node enlargement prospectively underwent standardised ultrasound examinations
      using B-mode sonography and native and contrast-enhanced CCDS and PD immediately
      before biopsy. Solbiati-Index (longitudinal-transverse diameter ratio) and
      intranodal flow patterns by using different vascularisation types were assessed.
      Histological and sonographical findings were correlated. RESULTS: 27 malignant
      and 5 benign lymph nodes were found. Solbiati-Index was lower in malignant lymph
      nodes than in benign nodes (mean 1.5 vs. 2.4, P<0.045). More intranodal flow
      patterns could be detected after UCA (53 vs. 43) but the number of correctly
      identified malignant nodes decreased after UCA (26 vs. 24) and the number of
      correctly identified benign nodes remained constant compared with native CCDS and
      PD. In 31% of the colour-mode studies, PD was considered to visualise more
      clearly intranodal vascular flow patterns than CCDS. CONCLUSION: despite
      depicting more intranodal vascular patterns, the use of an ultrasound contrast
      agent seems not to improve the diagnostic value of CCDS and PD compared with
      native colour-mode studies in superficial lymph node enlargement.

PMID- 14652143
TI  - Chest radiography and thoracic computed tomography findings in children who have
      family members with active pulmonary tuberculosis.
AB  - OBJECTIVE: The chest radiography and TCT findings in children who had contacted
      with adult family members with active pulmonary tuberculosis were compared. The
      contributions of thoracic computed tomography to the diagnosis of tuberculosis
      were investigated. METHODS AND MATERIAL: The children who were 0-16 years old
      (n=173) and children of families with an adult member which was diagnosed as
      pulmonary tuberculosis were evaluated. The children were considered in two groups
      based on the absence (n=125) or presence (n=48) of complaints and/or ambiguous
      symptoms such as lack of appetite, mild cough, sweating, history of lung
      infection, low body weight and those with suspicious chest radiography findings
      (12 cases) were included in this study. Asymptomatic patients (n=125) did not
      undergo TCT. Patients who had positive PPD skin tests only received isoniazid. If
      the TCT demonstrated enlarged lymph nodes or parenchymal lesions, minimally
      active pulmonary tuberculosis was diagnosed and antituberculous treatment was
      given. RESULTS AND DISCUSSIONS: TCT revealed lymph node enlargement or
      parenchymal lesions in 39 children (81.2%). Of the 12 children whose CXRs
      revealed suspicious lymph node enlargement and/or infiltration, five had normal
      findings in TCT whereas the initial findings were confirmed in the remaining
      seven. These data suggest that there is a correlation between the presence of
      ambiguous symptoms in exposed children and TCT findings; chest radiography and
      TCT findings do not yield parallel findings. All the patients who received anti
      TB treatment were resolved in the control examinations. CONCLUSION: In this study
      there is a correlation between presence of ambiguous symptoms and TCT findings,
      but the chest radiography and TCT findings do not yield harmony in exposed
      children with ambiguous symptoms (suspicious tuberculosis cases). These
      observations should be considered in children with symptoms similar to those of
      exposed children, but with no definite history of exposure. If similar TCT
      findings observed in such patients, treatment for tuberculosis should be
      considered.

PMID- 14652144
TI  - Transthoracic needle biopsy: factors effecting risk of pneumothorax.
AB  - OBJECTIVE: to evaluate the factors that could effect the risk of pneumothorax in
      patients undergoing transthoracic biopsy. MATERIAL AND METHODS: variables that
      could increase the risk of pneumothorax were evaluated in 453 CT-guided
      transthoracic biopsies. Factors were evaluated in two groups: (1) lesion related
      (presence of emphysema around the lesion, lesion depth, cavitation, presence of
      fissure/atelectasis and pleural tag in the needle trajectory); and (2) procedure
      related (biopsy type, needle size, number of passages, level of experience of the
      operator). All variables were analysed by chi2 test and multivariate logistic
      regression statistics. RESULTS: pneumothorax was developed in 85 (18.8%) out of
      453 procedures. A chest tube was inserted in ten (11.7%) of them. Variables that
      were significantly associated with an increased risk of pneumothorax were depth
      of the lesion (P<0.001) and severity of the emphysema (P<0.01). CONCLUSION: the
      length of the lung parenchyma traversed during the biopsy is the predominant risk
      factor for pneumothorax in patients undergoing CT-guided transthoracic biopsy.
      The risk of pneumothorax was also increased with the severity of the emphysema
      around the lesion.

PMID- 14652145
TI  - Radiation exposure to cardiologists performing interventional cardiology
      procedures.
AB  - Medical doctors, who practice interventional cardiology, receive a noticeable
      radiation dose. In this study, we measured the radiation dose to 9 cardiologists
      during 144 procedures (72 coronary angiographies and 70 percutaneus translumined
      coronary angioplasties) in two Greek hospitals. Absorbed doses were measured with
      TLD placed underneath and over the lead apron at the thyroid protective collar.
      Based on these measurements, the effective dose was calculated using the Niklason
      method. In addition, dose area product (DAP) was registered. The effective doses,
      E, were normalised to the total DAP measured in each procedure, producing the
      E/DAP index. The mean effective dose values were found to be in the range of 1.2
      2.7 microSv while the mean E/DAP values are in the range of 0.010-0.035
      microSv/Gycm2. The dependence of dose to the X-ray equipment, the exposure
      parameters and the technique of the cardiologist were examined. Taking under
      consideration the laboratories' annual workload, the maximum annual dose was
      estimated to be 1.9 and 2.8 mSv in the two hospitals.

PMID- 14652146
TI  - Automated vessel edge detection in velocity-encoded cine-MR (VEC-MR) flow
      measurements: a retrospective evaluation in critically ill patients.
AB  - OBJECTIVE: To assess feasibility of automated edge detection in magnetic
      resonance (MR) flow calculations in a clinical setting with critically ill
      patients. MATERIAL AND METHODS: Velocity encoded cine-MR (VEC-MR) flow
      measurements cross-sectional area (CSA), mean spatial velocity (MSV),
      instantaneous flow (IF), flow (F), 0.5 T Philips, TR 800-800, TE=8 ms, 30 degrees
      flip angle, FOV 280 mm, 128 x 256 matrix, temporal resolution 16 time frames/RR,
      VENC=120 cm/s) were obtained in 20 major thoracic human vessels (ascending aorta,
      main, right and left pulmonary artery-AAO, MPA, RPA, LPA) of five patients,
      suffering from severe chronic thromboembolic pulmonary hypertension (CTEPH). Flow
      maps were evaluated by two independent observers using conventional manual edge
      detection (INTER m/m). Flow calculations were performed by one observer using
      both, manual and automated edge detection (INTRA m/a), by a second observer using
      automated edge detection two times (INTRA a/a) and by two independent observers
      using automated edge detection (INTER a/a). Evaluation time was measured. Linear
      regression analysis and Student's t-test were performed. RESULTS: Overall
      regression coefficients (r2) for INTER m/m, INTRA m/a, INTER a/a and INTRA a/a,
      respectively, were as follows: CSA, 0.91, 0.91, 0.96, 0.98; MSV, 0.97, 0.99,
      0.99, 0.99; IF, 0.98, 0.99, 0.99, 0.99; F, 0.98, 0.99, 0.99, 0.99. Manual CSA
      values differed significantly from automated data in MPA (P=0.01), RPA (P=0.0008)
      and LPA (P=0.02). No difference was found for the other assessed parameters of
      the pulmonary circulation. Average evaluation time per vessel was 20.2+/-2.6 min
      for manual and 2.1+/-0.7 min for automated edge detection (P<0.00001).
      CONCLUSION: The software program used provided reproducible data, lead to a 90%
      reduction in evaluation and calculation time and, therefore, might excel the
      utilization of VEC-MR flow measurements. Despite variations in the evaluation of
      the pulmonary circulation CSAs, flow assessment is feasible in critically ill
      patients.

PMID- 14652147
TI  - Primary and metastatic rhabdomyosarcoma in the breast: report of two pediatric
      cases.
AB  - Rhabdomyosarcoma (RMS) is a common childhood malignancy which can rarely be
      located in the breast. Here, we report two pediatric cases of breast RMS, one
      primary, the other secondary involvement. Primary one is alveolar, and the other
      embryonal subtype. Imaging findings with ultrasonography (US), computed
      tomography (CT) and magnetic resonance imaging (MRI) and a thorough review of
      literature are presented.

PMID- 14652148
TI  - Preoperative estimation of the pathological breast tumour size by physical
      examination, mammography and ultrasound: a prospective study on 105 invasive
      tumours.
AB  - OBJECTIVE: The clinical breast tumour size can be assessed preoperatively by
      physical examination, mammography and ultrasound. At present it is not clear
      which modality correlates best with the histological invasive breast tumour size.
      This prospective study aims to determine the most accurate clinical method
      (physical examination, mammography or ultrasound) to predict the histological
      invasive tumour size preoperatively. METHODS AND PATIENTS: Between October 1999
      and August 2000, 96 women with 105 invasive malignant breast tumours were
      included in this study. All patients underwent excision and the tumour size was
      measured on histology. Tumour size was measured by all three modalities in 73
      cases. Results were evaluated by calculating correlation coefficients. The
      examination modalities presenting the best estimation of the pathological tumour
      size were used in a stepwise linear regression analysis to construct a formula
      predicting the pathological tumour size from the result of the various diagnostic
      modalities. RESULTS: The correlation coefficient between ultrasound and
      pathological size (r=0.68) was significantly better than the correlations between
      physical examination and pathological size (r=0.42) and mammographic and
      pathological size (r=0.44). Physical examination overestimates and ultrasound
      underestimates breast tumour classification. The most accurate prediction formula
      was: Pathological tumour size (mm) equals sonographic tumour size (mm)+3 mm.
      CONCLUSION: When comparing physical examination, mammography and ultrasound for
      the prediction of the pathological size of a malignant breast tumour, ultrasound
      is the best predictor. The ensuing regression formula determines pathological
      size as tumour size by ultrasound+3 mm. However, with the wide 95% confidence
      interval of +/-11 mm, it remains difficult to predict the exact pathological size
      for an individual invasive breast tumour. A small deviation in millimetres of the
      tumour size could lead to a change in treatment and to another prognostic
      estimate.

PMID- 14652149
TI  - Inflammatory pseudotumor of the liver in a patient with congenital
      granulocytopenia and HCV infection.
AB  - Inflammatory pseudotumor (IPT) of the liver is a rare pathologic lesion. Although
      IPTs within the liver shows spontaneous regression, these lesions are frequently
      misdiagnosed as malignant on the basis of the clinical manifestation and the
      results of diagnostic imaging. With special regard to magnetic resonance imaging
      (MRI), differential diagnosis such as hepatocellular or cholangiocellular
      carcinoma (HCC/CCC) as well as regenerative liver lesions are discussed in a case
      of IPT with concomitant hepatitis C virus (HCV) infection and congenital
      granulocytopenia.

PMID- 14652150
TI  - The efficacy of helical CT in the diagnosis of small bowel obstruction.
AB  - OBJECTIVE: To evaluate the usefulness and reliability of helical computed
      tomography (CT) for patients with small bowel obstruction. METHODS AND MATERIAL:
      Helical CT findings of 41 patients were evaluated prospectively on the basis of
      the presence and the cause of obstruction, and the presence of strangulation.
      RESULTS: In the determination of the cause of the obstruction sensitivity and
      specificity of CT were 84 and 90%, respectively. Of the 19 patients undergoing
      surgery, 6 had strangulation and were correctly identified by CT. CONCLUSION:
      Helical CT is an accurate method in the detection of small bowel obstruction,
      especially for evaluating the cause and vascular complications of obstruction.

PMID- 14652151
TI  - Usefulness of contrast-enhanced wide-band Doppler ultrasonograpy to diagnose
      alveolar echinococcosis of the liver and evaluate the effect of the treatment.
AB  - Alveolar echinococcosis is a rare parasitic disease caused by Echinococcus
      multicularis and most commonly involves the liver. Early diagnosis and accurate
      evaluation of the effect of the treatment are essential to improve the prognosis
      of patients with alveolar echinococcosis of the liver (AEL). The aim of this
      study was to demonstrate the characteristic imaging of AEL by contrast-enhanced
      Dynamic Flow (CE-DF) employing a wide-band Doppler technique for the diagnosis
      and the accurate evaluation of the effect of the treatment. Four patients with
      five AEL lesions before treatment or during medication were examined by CE-DF.
      All of the five AEL lesions examined by CE-DF revealed a defect with an irregular
      and distinct margin like a worm-eaten defect appearance, which was never observed
      on other hepatic lesions, in liver perfusion image during post-vascular phase. In
      addition, CE-DF made it possible to measure the size of AEL lesions accurately
      because the margin was detected distinctly. These data suggest that CE-DF is
      clinically useful for the diagnosis of AEL and the evaluation of the effect of
      the treatment.

PMID- 14652152
TI  - Quiz case. Extraabdominal desmoid tumor of the upper arm.

PMID- 14652153
TI  - Rapid estimation of the vertebral body volume: a combination of the Cavalieri
      principle and computed tomography images.
AB  - OBJECTIVE: The exact volume of the vertebral body is necessary for the
      evaluation, treatment and surgical application of related vertebral body.
      Thereby, the volume changes of the vertebral body are monitored, such as
      infectious diseases of vertebra and traumatic or non-traumatic fractures and
      deformities of the spine. Several studies have been conducted for the assessment
      of the vertebral body size based on the evaluation of the different criteria of
      the spine using different techniques. However, we have not found any detailed
      study in the literature describing the combination of the Cavalieri principle and
      vertebral body volume estimation. MATERIALS AND METHODS: In the present study we
      describe a rapid, simple, accurate and practical technique for estimating the
      volume of vertebral body. Two specimens were taken from the cadavers including
      ten lumbar vertebras and were scanned in axial, sagittal and coronal section
      planes by a computed tomography (CT) machine. The consecutive sections in 5 and 3
      mm thicknesses were used to estimate the total volume of the vertebral bodies by
      means of the Cavalieri principle. Furthermore, to evaluate inter-observer
      differences the volume estimations were carried out by three performers. RESULTS:
      There were no significant differences between the performers' estimates and real
      volumes of the vertebral bodies (P>0.05) and also between the performers' volume
      estimates (P>0.05). The section thickness and the section plains did not affect
      the accuracy of the estimates (P>0.05). A high correlation was seen between the
      estimates of performers and the real volumes of the vertebral bodies (r=0.881).
      CONCLUSION: We concluded that the combination of CT scanning with the Cavalieri
      principle is a direct and accurate technique that can be safely applied to
      estimate the volume of the vertebral body with the mean of 5 min and 11 s
      workload per vertebra.

PMID- 14652155
TI  - Soluble Fas antigen and soluble Fas ligand in early neonatal life.
AB  - BACKGROUND: After birth, apoptosis rates might slow down, compared to those in
      utero. Thus, factors, attenuating the apoptotic process, like the soluble forms
      of Fas/FasL system, may increase. AIM-STUDY DESIGN: Soluble Fas (sFas) and
      soluble Fas ligand (sFasL) concentrations were measured in maternal serum (MS),
      umbilical cord (UC) and neonatal serum in the first (1N) and fifth (5N) days
      after birth in order to evaluate the alterations of these molecules during the
      early neonatal period. SUBJECTS AND METHODS: Soluble molecules were estimated in
      35 healthy, appropriate for gestational age, full-term neonates, their mothers
      and in 25 healthy, nonpregnant women, age-matched to the mothers (controls),
      using enzyme immunoassays. RESULTS: sFas concentrations in MS (p < 0.01), UC (p <
      0.0001), 1N (p < 0.0003) and 5N (p < 0.02) were lower than those in controls.
      Neonatal sFas concentrations showed a significant increase from UC to 5N (p <
      0.001). In contrast, sFasL concentrations were significantly elevated in all
      neonatal samples (UC, 1N and 5N) compared to those in MS and controls (p <
      0.0001), showing also a significant elevation from UC to 5N (p < 0.0001).
      CONCLUSION: Our results demonstrate increasing serum concentrations of the
      soluble molecules sFas and sFasL during the first days after birth, indicating
      possibly a gradual decrease of apoptosis in early neonatal life.

PMID- 14652156
TI  - Deciduous tooth crown size in prematurely born children.
AB  - AIM: The purpose of our study was to examine deciduous tooth crown size in
      preterm children. SUBJECTS AND METHODS: The subjects consisted of 328 prematurely
      born (< 37 gestational weeks) white and black children and 1804 controls, who
      participated in the cross-sectional study of the Collaborative Perinatal Project
      (USA) in the 1960s and 1970s. Documents of the present research consisted of
      dental casts of the 6-12 years old children. Tooth crown measurements on canines
      and molars were performed on the dental casts with an electronic measuring device
      according to precise definitions generally quoted in the anthropological and
      genetic literature. For the results, the preterm and control groups were divided
      by sex and race. RESULTS: There were both increased and decreased mesiodistal and
      labiolingual tooth crown dimensions in prematurely born children, but no
      significant differences between the study groups was found. CONCLUSIONS: The
      findings of the present research suggest that short gestation is not associated
      with reduced deciduous tooth crown size as suggested by earlier studies and are
      parallel with our previous results of permanent tooth crown dimensions in
      prematurely born children. Boys showed clearly larger tooth crown sizes than
      girls within all preterm and control groups. This indicates that sexual
      dimorphism is apparent in its final form beginning some months after birth.

PMID- 14652157
TI  - Effect of antenatal exposure to maternal smoking on behavioural problems and
      academic achievement in childhood: prospective evidence from a Dutch birth
      cohort.
AB  - AIM: To examine effects of maternal smoking during pregnancy on academic
      achievement and emotional and behavioural problems during childhood. METHODS:
      Least squares regression was used to examine associations between maternal
      smoking prior to delivery and subsequent academic performance and behaviour of
      1186 children aged 5.5-11 years. Crude associations were adjusted for risk
      factors that were significantly related to the respective outcomes. MAIN OUTCOME
      MEASURES: Parents and teachers were asked to indicate, on a 10-item
      questionnaire, whether they regarded the child as more, the same, or less
      shy/withdrawn (internalising), troublesome (externalising), and attention
      deficient than the average child. Reading, spelling, and arithmetic performance
      levels were assessed with short standardised Dutch tests. RESULTS: After
      adjustment for confounders like socio-economic status and pre- and perinatal
      complications, children of mothers who smoked during pregnancy showed more signs
      of attention deficit and displayed higher levels of troublesome (externalising)
      behaviour than non-cigarette-exposed children. Also, children of smoking mothers
      performed worse on arithmetic and spelling tasks. Spelling problems were more
      pronounced when the mother continued to smoke after the child's birth.
      Excessively withdrawn (internalising) behaviour was not related to maternal
      smoking but to factors like the mother's use of psychotropic drugs and bottle
      instead of breastfeeding. CONCLUSION: Perinatal antecedents of internalising
      behaviour on the one hand and externalising behaviour, attention deficit, and
      learning problems on the other seem to be distinct. Only the latter are
      independently associated with maternal smoking during pregnancy and thus
      potentially amenable to early preventive effort, for instance, through continued
      health education emphasising the health hazards of nicotine use by pregnant
      women.

PMID- 14652158
TI  - Delivery modes and neonatal EEG: spatial pattern analysis.
AB  - BACKGROUND: Animal studies indicate that postnatal adaptation and development of
      neonates could be different due to the birth method and that these effects may
      last throughout adulthood. STUDY DESIGN: We applied a spatio-temporal analysis to
      EEG recordings of a group of neonates to investigate the influence of a cesarean
      section on maturation and extrauterine adaptation of the brain. EEG were recorded
      at 2 h and at 24 h after delivery. SUBJECTS: A spectral analysis technique, the
      so-called Karhunen-Loeve (KL) method, was applied to EEG of 10 neonates from
      vaginal delivery and 17 from C-section to obtain the spatio-temporal
      eigenpatterns. RESULTS: Spatio-temporal analysis showed noticeable pattern
      differences between the two groups. Compared to the C-section, the vaginal
      delivered neonate's EEG recordings showed a significant increase of amplitude at
      Fp1 in the pattern 24 h after the delivery, but not 2 h after delivery. Dynamics
      in this spectral analyses were not significantly different between both groups 2
      h after delivery, but the regional differences increased during the next day
      between both groups. CONCLUSIONS: This could come from the early insufficient
      complexity in C-section neonates. Global EEG complexity in C-section neonates
      fell short of that of vaginal delivered neonates 2 h after delivery. Many aspects
      of pattern change in C-section neonates followed the nature of vaginal delivered
      neonates. These could be considered as parts of a retarded transition of C
      section neonates in the early adaptation, but some of the differences in global
      EEG pattern could not be explained in this way. Pattern analysis suggests that
      the neuronal activities of the neonatal brain are changing regionally concurrent
      with bi-hemispheric global dynamics. Moreover, the delivery modes could have an
      influence on the early postneonatal adaptation of the physiological activity in
      brain.

PMID- 14652159
TI  - Analysis of the sounds of the child in the first year of age and a comparison to
      the language.
AB  - This study has the aim to analyze the acoustic characteristic features of cries
      and babbling in the course of the ontogenetical development of babies from the
      3rd to 5th day on up to the age of 1 year and to compare the results to the
      acoustic characteristics of the adult language. The mean fundamental frequency of
      crying increased considerably from 441.8 to 502.9 Hz and the mean fundamental
      frequency of babbling decreased remarkably from 389.3 to 336.9 Hz. These types of
      melodies represent individual differences in the course of crying. The first
      intonations were similar to the hunger cry and later they were on par with the
      pain cry. The melodies of babbling remained unchanged in the first year of age.
      Scientific examinations proved that crying and babbling are different. The
      development of the mean fundamental frequency for both, crying and babbling,
      showed a contrary tendency within the first year of age. The melody of babbling
      indicated similarities to the language within the first year of age. At the age
      of 9 months, the fundamental frequency and the melody contained features of the
      language of females in labour. Crying of a newborn and infant can be regarded in
      direct connection with the cries of a grown-up person, particularly in situations
      of emotional agitation or cultic rituals. Babbling, in contrast, shows structural
      similarities to the language. This justifies the assumption that the human being
      possesses two separate communication systems that share the same acoustic
      channel.

PMID- 14652160
TI  - Anti-reflux surgery for the neonatal intensive care-dependent infant.
AB  - AIM: The benefit of anti-reflux surgery for gastro-oesophageal reflux (GOR) in
      early infancy is uncertain. The aim of this study was to assess the value of
      Nissen fundoplication in a group of infants with severe GOR. METHODS: 10 infants
      underwent Nissen fundoplication for gastro-oesophageal reflux following a failure
      of medical management. All had suffered life-threatening respiratory episodes as
      a consequence of gastro-oesophageal reflux, and were neonatal intensive care
      dependent. Median (range) birth weight was 1.26 kg (0.48-3.8 kg), gestation 30
      weeks (25-38 weeks); at surgery, weight was 3.25 kg (2.5-6.1 kg) at a corrected
      age of 11.5 weeks (term-22) weeks. For each infant, the success of enteral
      feeding and the level of support required pre- and post-operatively was compared,
      and where appropriate, the facilitation of palliative feeding was assessed.
      Median follow-up was 14 (3-36) months. RESULTS: No infant suffered intra
      operative morbidity or mortality. One infant died within 1 month of surgery from
      a collapse unrelated to surgery. Eight of nine surviving infants were discharged
      from intensive care following extubation and the establishment of enteral
      feeding. One patient died of severe bronchopulmonary dysplasia 3 months post
      surgery. One infant developed a gastrostomy site infection, and two required
      gastrostomy tube replacement within 6 months of surgery. All were thriving at
      follow-up. Two infants with a congenital myopathy died as a result of their
      muscle disease at 9 and 11 months post-operatively. CONCLUSIONS: Nissen
      fundoplication is a feasible, effective and safe operation in severe gastro
      oesophageal reflux unresponsive to medical treatment in term and pre-term
      infants. It has an additional important role in facilitating safe palliative
      enteral feeding in infants with a diagnosis incompatible with survival into
      adulthood.

PMID- 14652161
TI  - Is hypotension a major risk factor for neurological morbidity at term age in very
      preterm infants?
AB  - OBJECTIVE: To investigate the influence of perinatal risk factors, especially
      hypotension, on neuromotor status at term in surviving preterm infants born
      before 32 weeks of gestation. METHODS: This study is part of the Leiden Follow-Up
      Project on Prematurity: a prospective, regional study of 266 live born infants
      with a gestational age (GA) < 32 weeks born in 1996-1997. Twenty-eight infants
      died before term age. Two hundred and eleven infants were examined neurologically
      at term according to Prechtl. The findings were classified as normal (N), mildly
      abnormal (MA) or definitely abnormal (DA). Hypotension was defined as a mean
      arterial blood pressure (MABP) < 30 mm Hg on at least two occasions. RESULTS: One
      hundred and six (50%) infants were classified as neurologically N, 92 (44%)
      infants were classified as MA and 13 (6%) infants as DA. Hypotension,
      bronchopulmonary dysplasia (BPD), flaring and cystic periventricular leucomalacia
      (PVL) were risk factors for neurological morbidity. Of the 68 infants with
      hypotension, 33 (49%) were classified as MA and 7 (10%) as DA. Of the 141 infants
      without hypotension, 58 (41%) were MA, and 5 (4%) were DA. The odds ratio of
      hypotension for neurological morbidity was 1.9 (95% CI 1.06-3.40), adjusted for
      gestational age, birth weight, small for gestational age (SGA) and gender, it was
      1.96 (95% CI 1.02-3.77). The adjusted odds ratio of PVL was 18.6 (4.4-78.5), of
      flaring was 2.37 (1.18-4.74) and of BPD was 2.44 (1.08-5.5). CONCLUSIONS: Apart
      from gestational age, periventricular leucomalacia, and bronchopulmonary
      dysplasia, hypotension in preterm infants is a major risk factor for neurological
      morbidity at term.

PMID- 14652162
TI  - Development of manipulative hand movements during the second year of life.
AB  - BACKGROUND: Developmental testing in children is concerned mainly with a pass or
      fail on tasks such as grasping, manipulating and inserting. Knowledge about the
      qualitative development of hand movements in young children is scarce. AIM: We
      studied the qualitative development of manipulative hand movements in 14-, 18-
      and 25-month-olds. STUDY DESIGN AND SUBJECTS: Twenty-six children were videoed
      during grasping, manipulating and inserting cubes into a cup or box and pegs into
      a peg-board. RESULTS: We found clear-cut, object-related results. The right hand
      was used mainly to grasp, manipulate and insert the pegs, while no hand
      preference was found for the cube. Generally, the quality of grasping and
      inserting did not change with age. At 18 months, the performance was more optimal
      if the children used pegs rather than cubes. The adjustment of hand opening
      became more adapted with increasing age when grasping the cubes; this was not
      observed for the pegs. Associated movements occurred less during pegging than
      while playing with the cubes. A variety of patterns were used for pegging.
      Besides a difference in hand preference between girls and boys, some patterns
      became more prominent with increasing age. The success rate increased with age
      but was independent of the pattern used. CONCLUSION: This study stresses the need
      of a clear understanding of the entire spectrum of normal motor development. This
      knowledge forms the basis on which abnormalities, even of such common movement
      patterns as grasping, manipulating and inserting, can be reliably diagnosed in
      neurologically impaired infants and children.

PMID- 14652163
TI  - Enteroviruses and type 1 diabetes mellitus.
AB  - Despite decades of research, the etiology of type 1 diabetes mellitus (DM) is
      unknown. Several risk factors have been associated with type 1 DM, including
      viral infections, genetic predisposition, nutritional factors, and chemicals.
      Several investigators hypothesize that the etiologies of type 1 DM result from a
      complex interaction of genetic and environmental factors. In this paper we review
      the epidemiologic data linking enteroviruses to type 1 DM and discuss potential
      mechanisms of pathogenesis.

PMID- 14652164
TI  - Trace elements in human physiology and pathology. Copper.
AB  - Copper is a trace element, important for the function of many cellular enzymes.
      Copper ions can adopt distinct redox states oxidized Cu(II) or reduced (I),
      allowing the metal to play a pivotal role in cell physiology as a catalytic
      cofactor in the redox chemistry of enzymes, mitochondrial respiration, iron
      absorption, free radical scavenging and elastin cross-linking. If present in
      excess, free copper ions can cause damage to cellular components and a delicate
      balance between the uptake and efflux of copper ions determines the amount of
      cellular copper. In biological systems, copper homeostasis has been characterized
      at the molecular level. It is coordinated by several proteins such as
      glutathione, metallothionein, Cu-transporting P-type ATPases, Menkes and Wilson
      proteins and by cytoplasmic transport proteins called copper chaperones to ensure
      that it is delivered to specific subcellular compartments and thereby to copper
      requiring proteins.

PMID- 14652165
TI  - Trace elements in human physiology and pathology: zinc and metallothioneins.
AB  - Zinc is one of the most abundant nutritionally essential elements in the human
      body. It is found in all body tissues with 85% of the whole body zinc in muscle
      and bone, 11% in the skin and the liver and the remaining in all the other
      tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40%
      is located in the nucleus, 50% in the cytoplasm, organelles and specialized
      vesicles (for digestive enzymes or hormone storage) and the remainder in the cell
      membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source,
      and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be
      essential to the structure and function of a large number of macromolecules and
      for over 300 enzymic reactions. It has both catalytic and structural roles in
      enzymes, while in zinc finger motifs, it provides a scaffold that organizes
      protein sub-domains for the interaction with either DNA or other proteins. It is
      critical for the function of a number of metalloproteins, inducing members of
      oxido-reductase, hydrolase ligase, lyase family and has co-activating functions
      with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++))
      does not participate in redox reactions, which makes it a stable ion in a
      biological medium whose potential is in constant flux. Zinc ions are hydrophilic
      and do not cross cell membranes by passive diffusion. In general, transport has
      been described as having both saturable and non-saturable components, depending
      on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of
      complexes with proteins and nucleic acids and participate in all aspects of
      intermediary metabolism, transmission and regulation of the expression of genetic
      information, storage, synthesis and action of peptide hormones and structural
      maintenance of chromatin and biomembranes.

PMID- 14652166
TI  - A molecular biological study of anti-tumor mechanisms of an anti-cancer agent
      Oxaliplatin against established human gastric cancer cell lines.
AB  - We report that preoperative administration of Oxaliplatin, a new anti-cancer
      platinum agent, is an effective treatment for gastric cancer. The purpose of this
      in vitro study is to determine whether Oxaliplatin induces apoptosis in
      established human gastric cancer cell lines. Five established gastric cancer cell
      lines are used: MNK45, KATO-III, OKAJIMA, MNK28 and MNK74. Chemosensitivity to l
      OHP is studied using a growth inhibition test. Induction of apoptosis in gastric
      cancer cells is analyzed by assessing DNA ladder formation, DNA fragmentation and
      actin cleavage. While all five gastric cancer cell lines are sensitive to
      Oxaliplatin, the poorly differentiated lines are the most sensitive. DNA ladder
      formation and/or DNA fragmentation are detected in all gastric cancer cell lines.
      However, actin cleavage is not detected in any of the cell lines. Oxaliplatin has
      an anti-cancer effect on human gastric cancer cell lines, particularly cell lines
      of poorly differentiated adenocarcinoma, indicating that Oxaliplatin would be an
      effective treatment for poorly differentiated gastric cancer. Oxaliplatin induces
      apoptosis in gastric cancer cell lines, but actin cleavage is not detected in
      cancer cells. This finding suggests that (1) the apoptotic caspase pathway leads
      mainly to DNA condensation and fragmentation, and (2) caspase-independent
      apoptotic pathways may be activated when gastric cancer cells are treated with
      Oxaliplatin.

PMID- 14652167
TI  - Effect of dietary selenite on N-nitrosodiethylamine-induced and phenobarbital
      promoted multistage hepatocarcinogenesis in rat: reflection in some minerals.
AB  - Selenium (Se), a dietary micronutrient, plays a vital role in cancer chemotherapy
      in many organs including the liver. We have studied the relationship between some
      minerals, which are essential in normal functioning of cells and anticancer
      effect of Se in N-nitrosodiethylamine (DEN) induced and phenobarbital (PB)
      promoted multistage hepatocarcinogenesis. Se (4 ppm through drinking water; as
      sodium selenite) was given to animals throughout the study, before initiation and
      during promotion phase of hepatocarcinogenesis, in a defined experimental
      protocol. Se, sodium, potassium, calcium and iron were measured either in
      hepatoma, or surrounding liver tissue or whole liver tissue and serum of
      experimental animals. DEN and PB treatment significantly (P < 0.001) increased
      potassium, calcium and iron levels in serum, while it decreased (P < 0.001) the
      Se and sodium levels when compared with control rats. We have also observed
      significantly increased (P < 0.001) sodium, calcium and iron levels in hepatoma
      and surrounding liver tissue, whereas, Se, and potassium level was found to be
      decreased (P < 0.001) when compared with control rats. Supplementation of
      selenite throughout the study, before initiation and during promotion stage
      significantly alters the above mineral content. Results showed that the most
      significant beneficial effect of selenium during hepatocarcinogenesis was exerted
      potentially in long-term continuous and/or before the initiation phase of
      carcinogenicity, rather than in the promotion phase. The present and previous
      results from our laboratory suggest that sub-optimal intake of a single trace
      mineral can have broad effects on chemotherapy, providing a framework for
      understanding the multiple beneficial effects of selenium in cancer
      chemoprevention.

PMID- 14652169
TI  - Transplantation treatment of spinal cord injury patients.
AB  - The minimally manipulated cells from fetal nervous and hemopoietic tissues
      (gestational age 16-22 weeks) were subarachnoidally implanted into 15 patients
      (18-52 years old) with severe consequences of traumatic spinal cord injury (SCI)
      at cervical or thoracic spine level. The times after SCI were from 1 month to 6
      years. Each patient underwent from one to four cell transplantations (CT) with
      various time intervals. In 11 of 15 cases, CT was combined with an operative
      partial disruption of a connective tissue cyst and with implantation into a
      spinal cord lesion of a spinal cord fragment together with olfactory ensheathing
      cells. Before CT the patients showed complete motor and sensory function disorder
      consistent with a grade A of SCI according to Frankel classification. With CT
      treatment, six patients improved their neurological status from A to C grade of
      SCI, exhibiting incomplete restoration of both motor and sensory function. The
      status of other five CT-treated patients became consistent with SCI grade B and
      was characterized by appearance of contracting activity in some muscles and
      incomplete restoration of sensitivity. The remaining four patients did not
      exhibit any clinical improvements. No serious complications of CT were noted. The
      results suggest a clinical relevance of the CT-based approach to treating severe
      consequences of SCI.

PMID- 14652168
TI  - Risk factors for lipodystrophy in the CISAI cohort.
AB  - PURPOSE: This study set out to describe the frequency of lipodystrophy, and
      identify its risk factors, in HIV-positive patients treated with HAART containing
      at least one protease inhibitor (PI). We analyzed the data collected in the CISAI
      study. METHODS: The CISAI is a multicenter cohort study that has enrolled 1480
      patients. We assessed whether patients had lipodystrophy at a medical visit, with
      follow-up visits by the same physician at least every 2 months, and also on the
      basis of patients' own reports. RESULTS: The lipodystrophy syndrome was detected
      in about 25% of the patients. Multivariate analysis showed the risk of
      lipodystrophy was correlated with female sex (RR 1.5; 95% confidence interval,
      CI, 1.2-2.1), with older age, with homosexuality (RR 1.5; 95% CI 1.0-2.4), with
      overt disease (RR 1.4; 95% CI 1.1-1.8) and with the duration of treatment before
      entering this study. The RR for ritonavir was higher than for the other PI (RR
      1.4; 95% CI 0.9-1.9). Among patients receiving concomitant antiretroviral therapy
      the risk of lipodystrophy was greater with stavudine (RR 1.7; 95% CI 1.3-2.3).
      CONCLUSIONS: The study confirmed the high frequency of the lipodystrophy syndrome
      among patients treated with PI.

PMID- 14652170
TI  - Modification by nimesulide administration of the phagocytic activity of
      polymorphonuclears of healthy subjects.

PMID- 14652172
TI  - NMR and microbiology: from physiology to metabolomics.
AB  - Recent advances in the application of NMR to microbiology are reviewed.
      Instrumental and methodological developments are described. The advantages and
      the constraints of NMR are illustrated with examples from the literature. Recent
      work from the authors' laboratories, taken as representative of current research
      in the field, is described in more detail.

PMID- 14652173
TI  - Lactate involvement in neuron-glia metabolic interaction: (13)C-NMR spectroscopy
      contribution.
AB  - Glucose is commonly admitted to be the main substrate for brain energy
      requirement. However, it has been recently proposed that lactate, generated from
      glucose via glycolysis, would be the oxidative substrate for neurons,
      particularly during neuronal activation, according to a mechanism called the
      astrocyte-neuron lactate shuttle hypothesis (ANLSH). In that mechanism, glutamate
      released in the synaptic cleft during brain activation is taken up by astrocytes.
      This uptake, via the glutamate/Na(+) transporter, induces the entry of sodium,
      which is then excluded from the astrocytes via the Na(+)/K(+) ATPase. This
      exclusion consumes ATP, which stimulates glycolysis and thus lactate formation in
      astrocytes. This lactate is then transferred to neurons where it is utilized as
      oxidative substrate. This review tries to gather the recent evidences that
      support this hypothesis and presents the contribution of NMR to this matter.

PMID- 14652174
TI  - Evidences on sodium ions compartmentalization in biological systems due to
      pathological states. A noninvasive NMR study.
AB  - Noninvasive nuclear magnetic resonance was used to measure the relaxation decay
      curves of naturally occurring 23Na ions in several biological systems.
      Experimental results showed an increase of membrane bound population for
      pathologic samples as compared with control. The bound sodium population was put
      in evidence using singular value decomposition method. Thus, the singular values
      that are obtained without any a priori from the fitting the relaxation decay
      curves are a new parameter in characterizing the cellular state. In the presence
      of artificial biological membranes, 23Na bound strongly to membranes containing
      phosphatidylcholine (PC) and phosphatidylserine (PS), but not to membranes
      consisting of only PC. A large bound population also appeared in the presence of
      apoptotic epithelial cells, which are known to translocate PS to the cell
      surface. A role for PS was confirmed by showing that sodium binds to the surface
      of epithelial cells infected with Chlamydia psittaci, and the amplitude of the
      bound population increases with a time-course similar to the appearance of PS on
      the surface of dying cells. Finally, this approach could distinguish between
      normal perfused liver and liver undergoing ischemia, due most likely to the
      exposure of surface PS on apoptotic and necrotic cells in the damaged tissue.
      Taken together, these studies demonstrate that the analysis of 23Na relaxation
      decay curves could reveal the presence of cells undergoing apoptosis and/or
      necrosis in living tissues. Noninvasive 23Na NMR measurements could thus be
      envisioned for controlling the quality of organs before transplantation, for the
      detection of asymptomatic infections that result in death of the host cell or
      inflammation of the tissue, and for characterizing the efficiency of novel
      apoptosis-inducing drugs to treat cancer.

PMID- 14652176
TI  - Non-invasive investigations of muscular fatigue: metabolic and electromyographic
      components.
AB  - Muscle fatigue, which is defined as the decline in muscle performance during
      exercise, may occur at different sites along the pathway from the central nervous
      system through to the intramuscular contractile machinery. Historically, both
      impairment of neuromuscular transmission and peripheral alterations within the
      muscle have been proposed to be involved in the development of fatigue. However,
      according to the more recent studies, muscle energetics would have a key role in
      this process. Intramyoplasmic accumulation of inorganic phosphate (P(i)) and
      limitation in ATP availability are frequently proposed as the causative factors
      of fatigue development. Although attractive, these hypotheses have been
      elaborated on the basis of experimental results obtained in vitro and their
      physiological relevance has never been clearly demonstrated in vivo. In that
      context, non-invasive methods such as 31-phosphorus magnetic resonance
      spectroscopy ((31)P MRS) and electromyographic (EMG) recordings have been
      employed to understand both metabolic and electrical aspects of muscle fatigue
      under physiological condition. The main results of these studies are reviewed in
      the present paper.

PMID- 14652175
TI  - Carbon 13 NMR spectroscopy: a powerful tool for studying renal metabolism.
AB  - Using precise examples, this paper shows that carbon 13 NMR spectroscopy in
      conjunction with radioactive and enzymatic methods as well as with adequate
      mathematical modeling of metabolic pathways allows not only to identify but also
      to quantify fluxes through enzymes involved in substrate and drug metabolism.
      Carbon 13 NMR spectroscopy is a tool of unprecedented power to unravel the
      complexity of renal metabolism. Currently it plays a major role in what is
      nowadays called metabolomics.

PMID- 14652177
TI  - Kinetics of anaerobic metabolism in human skeletal muscle: influence of
      repetitive high-intensity exercise on sedentary dominant and non-dominant
      forearm. A 31P NMR study.
AB  - Potential differences were assessed between the dominant (D) and non-dominant
      (ND) forearms of sedentary subjects during anaerobic exercise. Subjects performed
      voluntary concentric contractions of D and ND forearm muscle during a series of
      three high-intensity (60% of the maximal voluntary contraction force (MVC))
      exercise bouts. The time-dependent changes in intracellular pH (pH(i)), Pi, and
      PCr concentrations, and their relation to muscular work were examined using 31P
      magnetic resonance spectroscopy (MRS) techniques, and revealed that D forearm
      metabolic kinetics in sedentary individuals are improved during repetitive high
      intensity exercise compared to their respective ND forearm muscle. We postulate
      that the more regular and preferential utilization of the D limb leads to a
      "trained-like" condition.

PMID- 14652178
TI  - Multinuclear NMR investigations on the metabolic recovery of the isolated
      perfused mouse liver after cold preservation.
AB  - This paper describes multinuclear NMR investigations on the isolated perfused
      mouse liver to optimize its recovery after cold preservation and normothermic
      reperfusion. The recovery of livers from fed is better than that from 24 h fasted
      animals. This better recovery is not due to a higher glycogen content before cold
      preservation. The recovery of livers from fasted animals is specifically enhanced
      by the presence of 8 mM alanine in the rinsing solution after cold preservation
      and in the perfusate of reperfusion. This property is not due to the ability of
      alanine to compensate for the lack of endogenous substrates since the amount,
      before cold preservation, of these substrates, is not significantly different in
      livers from fed and fasted animals. Furthermore, the beneficial effect of alanine
      is not due to an enhancement of the pyruvate dehydrogenase (PDH) activity in
      livers from fasted animals. In fact these livers have indeed a smaller PDH
      activity than the livers from fed animals but dichloroacetate, a known PDH
      activator has a rather deleterious effect on the recovery of fed and fasted
      livers. Furthermore alanine protects the fasted livers against this effect. So
      the beneficial effect of alanine should be due to other causes. Furthermore, we
      have found on a parallel model of rat isolated perfused liver, that the recovery
      of steatotic livers which is lower than that of normal fed livers is enhanced by
      a known vasodilator, pentoxifylin but not by alanine. So alanine does not either
      play its role through its action on microcirculation. The interaction of alanine
      with some membrane sodium transporters like that already reported for another
      protective aminoacid, glycine, is thus possible. A novel NMR method of (23)Na
      observation in living cells or organs should be of great interest to investigate
      this hypothesis.

PMID- 14652179
TI  - Multimodal magnetic resonance imaging of the central nervous system.
AB  - The physiological and biochemical properties of the diseased brain that can be
      explored with magnetic resonance imaging (MRI) are increasing. Progress in MR
      based technology affords a large panel of MRI sequences that explore different
      phenomena and, thus, provide complementary informations. The diagnostic accuracy
      of MRI is improved by the combination of all MR modalities. However, this
      abundance of data requires an efficient multiparametric analysis to fully achieve
      the goal of the multimodal strategy. We will discuss the potential impact of this
      advanced MRI analysis in the clinical management and the therapeutical strategies
      of the most common brain pathologies (intracranial tumors, multiple sclerosis,
      stroke, epilepsy and dementia). This non-invasive approach is of utmost
      importance since it already improves the diagnosis and the therapeutic choice in
      the management of several central nervous system diseases.

PMID- 14652180
TI  - Perspectives with cryogenic RF probes in biomedical MRI.
AB  - Since discovery of high-temperature superconductive (HTS) ceramics by Bednorz and
      Muller in 1986, there has been an accelerated development of cold technologies in
      industry, including the domain of NMR detection. The purpose of this paper is to
      fix ideas about the stage that cryogenic radio frequency (RF) probe techniques
      have reached in biomedical magnetic resonance imaging (MRI). Readers confronted
      to the literature about this emerging topic have to understand a large range of
      motivations with somewhat unclearly defined technical limitations and actual
      outlets. An overview of sensitivity issues in the general context of biomedical
      MRI is provided here and the contribution of RF coil techniques to recent
      advances is identified. The domains where cooled coil materials such as copper,
      low- or high-temperature superconductors, could actually increase the RF coil
      sensitivity are delimited by a quantitative analysis of noise mechanisms.
      Technical keys, cryogenic means and cold RF coil technologies are considered, and
      first achievements in different fields of biomedical MRI are reviewed. This
      survey provides a basis for discussing about the future impact of cryogenic
      probes for MRI investigations.

PMID- 14652182
TI  - Fraying and electron autodetachment dynamics of trapped gas phase
      oligonucleotides.
AB  - Sensitive methods recently developed to measure laser-induced fluorescence from
      trapped ions have been applied to study the dynamics of double- and single
      stranded oligonucleotides. In this paper, the fraying of duplex terminal base
      pairs has been identified by measuring the donor fluorescence as a function of
      temperature from an oligonucleotide duplex labeled with a pair of FRET dyes.
      Comparison of the degree of dissociation of 14-mer duplexes observed in the mass
      spectra with the fluorescence intensity of the donor enables intermediate
      conformations of the unzipping duplex at the weaker binding end of the duplex to
      be identified. The autodetachment of electrons from double- and single-stranded
      oligonucleotide anions has been observed in a gas phase environment. To
      characterize this process, measurements were performed on 7-mers prepared without
      FRET fluorophores attached. The dependence of the decay rates of trapped anions
      have been measured as a function of charge state and temperature for various base
      compositions. An exceptionally strong dependence of the decay rate on base
      composition has been identified. The physical basis for this process will be
      discussed.

PMID- 14652183
TI  - Surface-induced dissociation of peptide ions: kinetics and dynamics.
AB  - Kinetics and dynamics studies have been carried out for the surface-induced
      dissociation (SID) of a set of model peptides utilizing a specially designed
      electrospray ionization Fourier Transform ion cyclotron resonance mass
      spectrometer in which mass-selected and vibrationally relaxed ions are collided
      on a orthogonally-mounted fluorinated self-assembled monolayer on Au [111]
      crystal. The sampling time in this apparatus can be varied from hundreds of
      microseconds to tens of seconds, enabling the investigation of kinetics of ion
      decomposition over an extended range of decomposition rates. RRKM-based modeling
      of these reactions for a set of polyalanines demonstrates that SID kinetics of
      these simple peptides is very similar to slow, multiple-collision activation and
      that the distribution of internal energies following collisional activation is
      indistinguishable from a thermal distribution. For more complex peptides
      comprised of several amino acids and with internal degrees of freedom (DOF) of
      the order of 350 there is a dramatic change in kinetics in which RRKM kinetics is
      no longer capable of describing the decomposition of these complex ions. A
      combination of RRKM kinetics and the "sudden death" approximation, according to
      which decomposition occurs instantaneously, is a satisfactory description. This
      implies that a population of ions-which is dependant on the nature of the
      peptide, kinetic energy and sampling time-decomposes on or very near the surface.
      The shattering transition is described quantitatively for the limited set of
      molecules examined to date.

PMID- 14652184
TI  - A model for energy transfer in inelastic molecular collisions applicable at
      steady state or non-steady state and for an arbitrary distribution of collision
      energies.
AB  - A new model for energy exchange between translational and internal degrees of
      freedom in atom-molecule collisions has been developed. It is suitable for both
      steady state conditions (e.g., a large number of collisions with thermal kinetic
      energies) and non-steady state conditions with an arbitrary distribution of
      collision energies (e.g., single high-energy collisions). In particular, it does
      not require that the collision energies be characterized by a quasi-thermal
      distribution, but nevertheless it is capable of producing a Boltzmann
      distribution of internal energies with the correct internal temperature under
      quasi-thermal conditions. The energy exchange is described by a transfer
      probability density that depends on the initial relative kinetic energy, the
      internal energy of the molecule, and the amount of energy transferred. The
      probability density for collisions that lead to excitation is assumed to decrease
      exponentially with the amount of transferred energy. The probability density for
      de-excitation is obtained from microscopic reversibility. The model has been
      implemented in the ion trap simulation program ITSIM and coupled with an Rice
      Rampsberger-Kassel-Marcus (RRKM) algorithm to describe the unimolecular
      dissociation of populations of ions. Monte Carlo simulations of collisional
      energy transfer are presented. The model is validated for non-steady state
      conditions and for steady state conditions, and the effect of the kinetic energy
      dependence of the collision cross-section on internal temperature is discussed.
      Applications of the model to the problem of chemical mass shifts in RF ion trap
      mass spectrometry are shown.

PMID- 14652185
TI  - Collisions of slow polyatomic ions with surfaces: the scattering method and
      results.
AB  - Surface-induced dissociation (SID) and reactions following impact of well-defined
      ion beams of polyatomic cations C2H5OH+, CH4+, and CH5+ (and its deuterated
      variants) at several incident angles and energies with self-assembled monolayers
      (SAM), carbon surfaces, and hydrocarbon covered stainless steel were investigated
      by the scattering method. Energy transfer and partitioning of the incident
      projectile energy into internal excitation of the projectile, translational
      energy of products, and energy transferred into the surface were deduced from the
      mass spectra and the translational energy and angular distributions of the
      product ions. Conversion of ion impact energy into internal energy of the
      recoiling ions peaked at about 17% of the incident energy for the perfluoro
      hydrocarbon SAM, and at about 6% for the other surfaces investigated. Ion
      survival probability is about 30-50 times higher for closed-shell ions than for
      open-shell radical cations (e.g., 12% for CD5+ versus 0.3% for CD4+, at the
      incident angle of 60 degrees with respect to the surface normal). Contour
      velocity plots for inelastic scattering of CD5+ from hydrocarbon-coated and
      hydrocarbon-free highly oriented pyrolytic graphite (HOPG) surfaces gave
      effective masses of the surface involved in the scattering event, approximately
      matching that of an ethyl group (or two methyl groups) and four to five carbon
      atoms, respectively. Internal energy effects in impacting ions on SID were
      investigated by comparing collision energy resolved mass spectra (CERMS) of
      methane ions generated in a low pressure Nier-type electron impact source versus
      those generated in a Colutron source in which ions undergo many collisions prior
      to extraction and are essentially vibrationally relaxed. This comparison supports
      the hypothesis that internal energy of incident projectile ions is fully
      available to drive their dissociation following surface impact.

PMID- 14652186
TI  - Gas-phase dissociation pathways of multiply charged peptide clusters.
AB  - Numerous studies of cluster formation and dissociation have been conducted to
      determine properties of matter in the transition from the condensed phase to the
      gas phase using materials as diverse as atomic nuclei, noble gases, metal
      clusters, and amino acids. Here, electrospray ionization is used to extend the
      study of cluster dissociation to peptides including leucine enkephalin with 7-19
      monomer units and 2-5 protons, and somatostatin with 5 monomer units and 4
      protons under conditions where its intramolecular disulfide bond is either
      oxidized or reduced. Evaporation of neutral monomers and charge separation by
      cluster fission are the competing dissociation pathways of both peptides. The
      dominant fission product for all leucine enkephalin clusters studied is a proton
      bound dimer, presumably due to the high gas-phase stability of this species. The
      branching ratio of the fission and evaporation processes for leucine enkephalin
      clusters appears to be determined by the value of z2/n for the cluster where z is
      the charge and n the number of monomer units in the cluster. Clusters with low
      and high values of z2/n dissociate primarily by evaporation and cluster fission
      respectively, with a sharp transition between dissociation primarily by
      evaporation and primarily by fission measured at a z2/n value of approximately
      0.5. The dependence of the dissociation pathway of a cluster on z2/n is similar
      to the dissociation of atomic nuclei and multiply charged metal clusters
      indicating that leucine enkephalin peptide clusters exist in a state that is more
      disordered, and possibly fluid, rather than highly structured in the dissociative
      transition state. The branching ratio, but not the dissociation pathway of
      [somatostatin5 + 4H]4+ is altered by the reduction of its internal disulfide bond
      indicating that monomer conformational flexibility plays a role in peptide
      cluster dissociation.

PMID- 14652187
TI  - Peptide sequencing using a patchwork approach and surface-induced dissociation in
      sector-TOF and dual quadrupole mass spectrometers.
AB  - Surface-induced ion activation in combination with a database search strategy
      based on the Patchwork concept is applied to the determination of peptide
      sequences. Surface-induced dissociation (SID) is performed in a tandem quadrupole
      mass spectrometer and in a hybrid sector/time-of-flight mass spectrometer in
      order to evaluate the importance of accurate mass analysis of the SID fragment
      ions for peptide identification. The modified Patchwork approach is based on
      piecing together the peptide blocks in a bidirectional way, simultaneously using
      low-mass fragments originating from the C-terminus and N-terminus of the
      molecule, and relying on the measurement of the peptide's molecular weight with
      moderate mass accuracy. The results from this analysis are used as search filters
      in MASCOT's (http://www.matrixscience.com) Sequence Query search engine, with the
      simultaneous addition of the full MS/MS peak list. SID is performed with
      collision targets coated with pure and mixed composition self-assembled
      monolayers produced by fluorocarbon and hydrocarbon alkanethiolate solutions of
      varying chemical composition. The resulting MS/MS spectra produced on pure and
      mixed hydrocarbon SAMs are submitted to the modified version of Patchwork
      sequencing. It is found that hydrocarbon surfaces improve the relative abundance
      of larger fragments. Under the moderate mass accuracy conditions (+/-0.3 u)
      offered by our linear-TOF-SID instrument, it is found that increasing the
      abundance of larger fragments dramatically improves the sequencing scores.

PMID- 14652188
TI  - Direct dynamics study of N-protonated diglycine surface-induced dissociation.
      Influence of collision energy.
AB  - A quantum mechanical and molecular mechanical (QM + MM) direct dynamics classical
      trajectory simulation is used to study energy transfer and fragmentation in the
      surface-induced dissociation (SID) of N-protonated diglycine, (gly)2H+. The
      peptide ion collides with the hydrogenated diamond [111] surface. The Austin
      Model 1 (AM1) semiempirical electronic structure theory is used for the (gly)2H+
      intramolecular potential and molecular mechanical functions are used for the
      diamond surface potential and peptide/surface intermolecular potential. The
      simulations are performed at collision energies Ei of 30, 50, 70, and 100 eV and
      collision angle of 0 degrees (perpendicular to the surface). The percent energy
      transfer to the peptide ion is nearly independent of Ei, while energy transfer to
      the surface increases with increase in Ei. A smaller percent of the energy
      remains in peptide translation as Ei is increased. These trends in energy
      transfer are consistent with previous trajectory simulations of SID. At each Ei
      the most likely initial pathway leading to fragmentation is rupture of the
      +H3NCH2-CONHCH2COOH bond. Fragmentation occurs by two general mechanisms. One is
      the traditional Rice-Ramsperger-Kassel-Marcus (RRKM) model in which the peptide
      ion is activated by its collision with the surface, "bounces off", and then
      dissociates after undergoing intramolecular vibrational energy redistribution
      (IVR). The other mechanism is shattering in which the ion fragments as it
      collides with the surface. Shattering is the origin of the large increase in
      number of product channels with increase in Ei, i.e., 6 at 30 eV, but 59 at 100
      eV. Shattering becomes the dominant dissociation mechanism at high Ei.

PMID- 14652189
TI  - Alternative approaches to infrared multiphoton dissociation in an external ion
      reservoir.
AB  - In this work we present variations on in-hexapole infrared multiphoton
      dissociation (IRMPD) for the characterization of modified oligonucleotides using
      an ESI-FTICR spectrometer. We demonstrate that IRMPD in the external ion
      reservoir provides a comprehensive series of fragments allowing thorough
      characterization of a wide range of oligonucleotides containing alternative
      backbones and 2' substitutions. An alternative pulse sequence is presented that
      allows alternating MS and IRMPD MS/MS spectra to be acquired on a chromatographic
      timescale without loss in ionization duty cycle. Ions are excited to a larger
      cyclotron radius such that they "dodge" the IR laser beam that travels through
      the center of the trapped ion cell and impinges on the external ion reservoir
      creating IRMPD fragments that will be detected in the next scan. An alternative
      approach for directing IR radiation into the external ion reservoir using a
      hollow fiber waveguide as a photon conduit is presented. This approach offers a
      simple and robust alternative to the previously utilized on-axis scheme and may
      allow effective implementation with lower power lasers owing to the inherent
      increase in power density achieved by focusing the nascent laser beam into the
      hollow fiber waveguide.

PMID- 14652190
TI  - Development of LC-IMS-CID-TOFMS techniques: analysis of a 256 component
      tetrapeptide combinatorial library.
AB  - Recent improvements in ion mobility/time-of-flight mass spectrometry techniques
      have made it possible to incorporate nano-flow liquid chromatography and
      collision induced dissociation techniques. This combination of approaches
      provides a new strategy for detailed characterization of complex systems--such
      as, combinatorial libraries. Our work uses this technology to provide a detailed
      analysis of a tetrapeptide library having the general form Xxx1-Xxx2-Xxx3-Xxx4
      where Xxx1 = Glu, Phe, Val, Asn; Xxx2 = Glu, Phe, Val, Tyr; Xxx3 = Glu, Phe, Val,
      Thr; and Xxx4 = Glu, Phe, Val, Leu--a system that is expected to contain 256
      different peptide sequences. The results corroborate the presence of many
      expected peptide sequences and indicate that some synthetic steps appear to have
      failed. Particularly interesting is the observation of a t-butyl protecting group
      on the tyrosine (Tyr) residue. It appears that most Tyr containing peptides that
      have this t-butyl group attached favor formation of [2M + 2H]2+ dimers, which can
      be readily distinguished from [M + H]+ monomers based on differences in their gas
      phase mobilities. In this case, we demonstrate the use of the mobility
      differences between [2M + 2H]2+ and [M + H]+ ions as a signature for a failure of
      a synthetic step.

PMID- 14652191
TI  - Differentiation of flavonoid glycoside isomers by using metal complexation and
      electrospray ionization mass spectrometry.
AB  - The elucidation of flavonoid isomers is accomplished by electrospray ionization
      tandem mass spectrometry (ESI-MS/MS) via formation and collisional activated
      dissociation (CAD) of metal/flavonoid complexes containing an auxiliary ligand.
      Addition of a metal salt and a suitable neutral auxiliary ligand to flavonoids in
      solution results in the formation of [M(II) (flavonoid-H) ligand]+ complexes by
      ESI which, upon collisional activated dissociation, often result in more
      distinctive fragmentation patterns than observed for conventional protonated or
      deprotonated flavonoids. Previously, 2,2'-bipyridine was used as an auxiliary
      ligand, and now we compare and explore the use of alternative pyridyl ligands,
      including 4,7-diphenyl-1,10-phenanthroline. Using this technique, three groups of
      flavonoid glycoside isomers are differentiated, including glycosides of apigenin,
      quercetin, and luteolin.

PMID- 14652192
TI  - Experimental and theoretical investigation of the main fragmentation pathways of
      protonated H-Gly-Gly-Sar-OH and H-Gly-Sar-Sar-OH.
AB  - The fragmentation pathways of protonated H-Gly-Gly-Sar-OH and H-Gly-Sar-Sar-OH
      are investigated by using both computational and experimental techniques. The
      main goal of these studies is to further investigate which factors determine the
      branching ratio of the b2-y1 (Paizs, B.; Suhai, S. Rapid Commun. Mass Spectrom.
      2002, 16, 375.) and "diketopiperazine" (Cordero, M. M.; Houser, J. J.;
      Wesdemiotis, C. Anal. Chem. 1993, 65, 1594.) pathways of protonated tripeptides.
      Protonated H-Gly-Sar-Sar-OH represents a sensitive test for the branching ratio
      of the b2-y1 and "diketopiperazine" pathways since this ion cannot produce y1
      ions on the b(-y1 channel but only b2 ions. Protonated H-Gly-Gly-Sar-OH and H-Gly
      Sar-Sar-OH exhibit very different fragmentation behavior under the investigated
      experimental conditions. The former fragments forming mainly y1 ions (maximum
      abundance of the b2 and y2 ions is approximately 15%), while the latter produces
      mainly b2 ions while at larger internal energies the a2, y2, and y1 ions become
      also moderately abundant. Theoretical modeling and analysis of the main
      fragmentation pathways indicate that the majority of the b2 and y1 ions of
      protonated H-Gly-Gly-Sar-OH and the b2 ions of H-Gly-Sar-Sar-OH are formed on the
      b2-y1 pathway.

PMID- 14652193
TI  - Quantitative evaluation of noncovalent chorismate mutase-inhibitor binding by ESI
      MS.
AB  - Electrospray time-of-flight mass spectrometry was used to quantitatively
      determine the dissociation constant of chorismate mutase and a transition state
      analogue inhibitor. This system presents a fairly complex stoichiometry because
      the native protein is a homotrimer with three equal and independent substrate
      binding sites. We can detect the chorismate mutase trimer as well as chorismate
      mutase-inhibitor complexes by choosing appropriate conditions in the ESI source.
      To verify that the protein-inhibitor complexes are specific, titration
      experiments with different enzyme variants and different inhibitors were
      performed. A plot of the number of bound inhibitors versus added inhibitor
      concentration revealed saturation behavior with 3:1 (inhibitor:functional trimer)
      stoichiometry for the TSA. The soft ESI conditions, the relatively high protein
      mass of 43.5 kDa, and the low charge state (high m/z) result in broad peaks, a
      typical problem in analyzing noncovalent protein complexes. Due to the low
      molecular weight of the TSA (226 Da) the peaks of the free protein and the
      protein with one, two or three inhibitors bound cannot be clearly resolved. For
      data analysis, relative peak areas of the deconvoluted spectra of chorismate
      mutase-inhibitor complexes were obtained by fitting appropriate peak shapes to
      the signals corresponding to the free enzyme and its complexes with one, two, or
      three inhibitor molecules. From the relative peak areas we were able to calculate
      a dissociation constant that agreed well with known solution-phase data. This
      method may be generally useful for interpreting mass spectra of noncovalent
      complexes that exhibit broad peaks in the high m/z range.

PMID- 14652194
TI  - The role of acidic residues and of sodium ion adduction on the gas-phase H/D
      exchange of peptides and peptide dimers.
AB  - Gas-phase H/D exchange is widely used for characterizing the structure of ions.
      However, many structural parameters that affect the rate of H/D exchange are
      poorly understood, which complicates the interpretation of experimental data.
      Here, the effects of sodium ion adduction on the rate of H/D exchange with D2O
      for a series of peptides and peptide dimers with varying numbers of acidic
      residues are described. The maximum number of sodium ion adducts that can be
      accommodated by the peptides and peptide dimers in this study is N + 1, where N
      is the number of free carboxylic acid groups. The formation of methyl-esters at
      all carboxylic acid groups, or the replacement of all the acidic hydrogens with
      sodium ions, effectively shuts down H/D exchange with D2O. In contrast, both the
      rate and the extent of H/D exchange with D2O are increased for most of the
      peptides and peptide dimers by the adduction of an intermediate number of sodium
      ions. These results are consistent with the H/D exchange occurring via a salt
      bridge mechanism and show that the presence of two carboxylic acid groups is much
      better than one. The results with peptide dimers also indicate that surface
      accessibility may not be a dominant factor in the extent of H/D exchange for
      these ions.

PMID- 14652195
TI  - Differentiation of isomeric C8-substituted alkylaniline adducts of guanine by
      electrospray ionization and tandem quadrupole ion trap mass spectrometry.
AB  - Product ion spectra from thirteen C8-substituted alkylaniline adducts of guanine
      and deoxyguanosine were generated using electrospray ionization and quadrupole
      ion trap mass spectrometry and studied to investigate the possibility of
      differentiating isomeric adduct structures based upon the relative abundances of
      fragment ions derived from the alkylaniline-modified guanine bases (BH2(+) ions).
      The structural discrimination of the BH2(+) ions formed by attachment of isomeric
      alkylanilines to the C8 position of guanine is a challenging problem because the
      ions tend to yield product ion spectra that are qualitatively identical upon
      collisional activation. In this study, a statistical method, referred to as a
      similarity index, was used to compare the product ion spectra of isomeric BH2(+)
      ions and differentiate their structures. All the adducts investigated could be
      distinguished from SIs calculated using 5-6 product ions. These results suggest
      that a searchable database of product ion spectra may be created and used to
      characterize DNA adducts from aromatic amines whenever they are detected at
      levels amenable to mass spectral analysis.

PMID- 14652196
TI  - Faith no more.

PMID- 14652197
TI  - Aedes albopictus in Africa.

PMID- 14652198
TI  - Hantavirus infections in Europe.

PMID- 14652200
TI  - Multidrug-resistant Shigella dysenteriae type 1 in south Asia.

PMID- 14652202
TI  - Leptospirosis: a zoonotic disease of global importance.
AB  - In the past decade, leptospirosis has emerged as a globally important infectious
      disease. It occurs in urban environments of industrialised and developing
      countries, as well as in rural regions worldwide. Mortality remains significant,
      related both to delays in diagnosis due to lack of infrastructure and adequate
      clinical suspicion, and to other poorly understood reasons that may include
      inherent pathogenicity of some leptospiral strains or genetically determined host
      immunopathological responses. Pulmonary haemorrhage is recognised increasingly as
      a major, often lethal, manifestation of leptospirosis, the pathogenesis of which
      remains unclear. The completion of the genome sequence of Leptospira interrogans
      serovar lai, and other continuing leptospiral genome sequencing projects, promise
      to guide future work on the disease. Mainstays of treatment are still
      tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention
      is largely dependent on sanitation measures that may be difficult to implement,
      especially in developing countries.

PMID- 14652203
TI  - Management of Candida species infections in critically ill patients.
AB  - Invasive candidiasis is a feared infection with mortality similar to that of
      septic shock (40-60%). Improved knowledge of its pathophysiology and the
      availability of new compounds for antifungal therapy and prophylaxis have
      contributed to improving the prognosis of severe candidal infections among
      immunosuppressed patients at the possible cost of the emergence of non-albicans
      strains of candida with lower susceptibility to azoles. This review focuses on
      the management of invasive deep-seated candidiasis in critically ill, non
      immunocompromised patients. We discuss antifungal use, indications, potential
      benefit, and main secondary effects. Prevention strategies include pre-emptive
      antifungal therapy and azole-based prophylaxis. For patients at lower initial
      risk, pre-emptive therapy should be based on a management strategy that takes
      into account the presence of definite risk factors and the dynamics of candida
      colonisation. Among critically ill patients, azole prophylaxis is effective and
      is not associated with acquisition of resistance; it must be restricted to highly
      selected groups of patients at high risk only.

PMID- 14652204
TI  - Breast milk and HIV-1: vector of transmission or vehicle of protection?
AB  - Transmission of HIV-1 to the infant through breastfeeding is a major cause of new
      paediatric HIV-1 infections worldwide. Although extended breastfeeding accounts
      for approximately 40% of infant HIV infections worldwide, most breastfed infants
      remain uninfected, despite prolonged and repeated exposure to HIV-1. Mechanisms
      associated with transmission of HIV-1 through breastfeeding and factors related
      to protection from such transmission remain poorly understood. Here we focus on
      the cellular origin of HIV in breast milk and on immune factors within the milk
      that may offer protection from transmission of HIV infection. The presence of
      innate immunity and induction of adaptive immunity against HIV is explored: in
      particular, specific antibodies, cellular responses, and their significance. The
      role of mucosal immune activation and epithelial integrity in HIV transmission is
      also addressed. We are of the opinion that advances in laboratory methods that
      study specific aspects of immunity will help open new areas of understanding of
      HIV transmission through breastfeeding and mechanisms of protection, and
      contribute to the development of novel prevention strategies.

PMID- 14652205
TI  - Biocide use and antibiotic resistance: the relevance of laboratory findings to
      clinical and environmental situations.
AB  - Antibiotics are used as chemotherapeutic drugs, and biocides are used as
      antiseptics, disinfectants, and preservatives. Several factors affect biocidal
      activity, notably concentration, period of contact, pH, temperature, the presence
      of interfering material, and the types, numbers, location, and condition of
      microorganisms. Bacterial cells as part of natural or artificial (laboratory)
      biofilm communities are much less susceptible than planktonic cells to
      antibiotics and biocides. Assessment of biocidal activity by bactericidal testing
      is more relevant than by determination of minimum inhibitory concentrations.
      Biocides and antibiotics may show some similarities in their mechanisms of action
      and common mechanisms of bacterial insusceptibility may apply, but there are also
      major differences. In the laboratory, bacteria can become less susceptible to
      some biocides. Decreased resistance may be stable or unstable and may be
      accompanied by a low-level increase in antibiotic resistance. Laboratory studies
      are useful for examining stress responses and basic mechanisms of action and of
      bacterial insusceptibility to antibacterial agents. Translation of such findings
      to the clinical and environmental situations to provide evidence of a possible
      relation between biocide use and clinical antibiotic resistance is difficult and
      should be viewed with caution.

PMID- 14652206
TI  - The challenge of Trypanosoma brucei gambiense sleeping sickness diagnosis outside
      Africa.
AB  - Sleeping sickness is a lethal African disease caused by parasites of the
      Trypanosoma brucei subspecies, which is transmitted by tsetse flies.
      Occasionally, patients are reported outside Africa. Diagnosis of such imported
      cases can be problematic when the infection is due to Trypanosoma brucei
      gambiense, the chronic form of sleeping sickness found in west and central
      Africa. The low number of trypanosomes in the blood and the non-specific,
      variable symptoms make the diagnosis difficult, particularly when the index of
      suspicion is low. When the trypanosomes have penetrated into the central nervous
      system, neuropathological signs become apparent but even at this stage,
      misdiagnosis is frequent. Rapid and correct diagnosis of sleeping sickness can
      avoid inappropriate or delayed treatment and even death of the patient. In this
      article, an overview on diagnosis of imported cases of T b gambiense sleeping
      sickness is given, and possible pitfalls in the diagnostic process are
      highlighted. Bioclinical parameters that should raise the suspicion of sleeping
      sickness in a patient who has been in west or central Africa are discussed.
      Techniques for diagnosis are reviewed. A clinician suspecting sleeping sickness
      should contact a national reference centre for tropical medicine in his or her
      country, or the WHO, Geneva, Switzerland, or the Centers for Disease Control and
      Prevention (CDC), Atlanta, GA, USA, for clinical consultation and provision of
      specific diagnostic tests. Appropriate drugs for sleeping sickness treatment are
      also provided by WHO and the CDC.

PMID- 14652207
TI  - Peter Piot-executive director of UNAIDS. Interview by Pam Das.

PMID- 14652209
TI  - Slow transformation.

PMID- 14652210
TI  - Modeling topographic effects on net ecosystem productivity of boreal black spruce
      forests.
AB  - Current regional estimates of net primary productivity (NPP) of boreal black
      spruce overlook the large variation in NPP caused by small-scale topographic
      effects on soil water, temperature and nutrient availability. Topographic effects
      on black spruce NPP could likely be modeled by simulating the lateral and
      vertical movement of water, and its effects on soil nutrient transformation and
      uptake, through three-dimensional watersheds defined by aspects and slopes of
      their topographic positions. To examine this likelihood, the ecosystem model
      'ecosys' was run for 120 years on a transect that included upper- and lower-slope
      positions and a basin in which a basal water table was set 0.5 m below the soil
      surface. For the run, we used soil properties and weather conditions recorded at
      the 115-year-old BOREAS Southern Old Black Spruce site. Short-term model
      performance was tested by comparing diurnal and annual carbon (C) transfers
      simulated under 1994 weather conditions during the 115th year of the model run
      with those measured at this site during 1994 by eddy covariance, surface chambers
      and allometry. After 115 years, annual spruce NPP simulated at the upper-slope
      positions was twice that at the basin (350 versus 170 g C m-2), whereas
      accumulated wood C was almost three times as large (6.8 versus 2.4 kg C m-2). In
      the model, increases in NPP and wood growth in upper-slope positions were caused
      by lower soil water contents, higher soil temperatures, and more rapid O2 uptake
      that accelerated heterotrophic respiration and hence nutrient mineralization and
      uptake. Modeled differences in wood growth with topographic position were
      quantitatively consistent with measurements of boreal black spruce at several
      research sites differing in water table depth. Modeled differences also agreed
      with differences in wood growth rates derived from allometric measurements at
      boreal black spruce sites differing in productivity indices as a result of
      differences in subsurface hydrology. The magnitude of these differences clearly
      indicates the importance of accounting for subsurface hydrology in regional
      estimates of boreal forest productivity.

PMID- 14652212
TI  - Influence of nutrient application rate on growth and rooting potential of the
      West African hardwood Triplochiton scleroxylon.
AB  - Effects of stock plant nutrition on growth and subsequent rooting of leafy stem
      cuttings of the commercially important west African tree Triplochiton scleroxylon
      K. Schum. were investigated to identify the primary morphological variables
      influencing adventitious root formation. Potted plants were watered as required
      with one of four balanced nutrient solutions (0, 15, 63 or 125 mg N l(-1)).
      Increasing the nutrient supply to stock plants increased growth rate and rate of
      adventitious root production of subsequently harvested cuttings, but an optimum
      nutrient regime was not identified. Rooting percentage increased from 27% in
      cuttings harvested from stock plants receiving a low nutrient supply to 64% for
      cuttings harvested from stock plants receiving eight times the amount of
      nutrients extractable from plants under typical field conditions in West Africa.
      The ability of a cutting to retain its leaf during propagation and the length of
      the cutting were the primary measured characteristics associated with rooting and
      accounted for 43% of the variance fitted in the model. The length of the new
      shoot, total leaf area and within-shoot position (node position) were also
      significantly associated with rooting. After these characteristics were fitted to
      the model, the genetic origin (clone) was not statistically significant. We
      conclude that genetic variation in rooting potential is mediated through
      variations in morphological and physiological traits, rather than through genetic
      variation in cell differentiation or related aspects of root initiation.

PMID- 14652211
TI  - Component carbon fluxes and their contribution to ecosystem carbon exchange in a
      pine forest: an assessment based on eddy covariance measurements and an
      integrated model.
AB  - We used a combination of eddy flux, canopy, soil and environmental measurements
      with an integrated biophysical model to analyze the seasonality of component
      carbon (C) fluxes and their contribution to ecosystem C exchange in a 50-year-old
      Scots pine forest (Pinus sylvestris L.) in eastern Finland (62 degrees 47' N, 30
      degrees 58' E) over three climatically contrasting years (2000-2002). Eddy flux
      measurements showed that the growing Scots pine forest was a sink for CO2, with
      annual net C uptakes of 131, 210 and 258 g C m-2> year-1 in 2000, 2001 and 2002,
      respectively. The integrated process model reproduced the annual course of daily
      C flux above the forest canopy as measured by the eddy covariance method once the
      site-specific component parameters were estimated. The model explained 72, 66 and
      68% of the variation in daily net C flux in 2000, 2001 and 2002, respectively.
      Modeled annual C loss by respiration was 565, 629 and 640 g C m-2 year-1,
      accounting for 77, 77 and 65% of annual gross C uptake, respectively. Carbon
      fluxes from the forest floor were the dominant contributors to forest ecosystem
      respiration, with the fractions of annual respiration from the forest floor,
      foliage and wood being 46-62, 27-44 and 9-10%, respectively. The wide range in
      daily net C uptake during the growing season was largely attributable to day-to
      day fluctuations in incident quantum irradiance. During just a few days in early
      spring and late autumn, ecosystem net C exchange varied between source and sink
      as a result of large daily changes in temperature. The forest showed a greater
      reduction in gross C uptake by photosynthesis than in C loss by respiration
      during the dry summer of 2000, indicating that interannual variability in
      ecosystem net C uptake at this site was modified mostly by summer rainfall and
      vapor pressure deficit.

PMID- 14652213
TI  - Morphological and physiological responses of beech (Fagus sylvatica) seedlings to
      grass-induced below ground competition.
AB  - We examined morphological and physiological responses of beech (Fagus sylvatica
      L.) seedlings to grass-induced below ground competition in full-light conditions.
      Two-year-old beech seedlings were grown during two growing seasons in 160-l
      containers in bare soil or with a mixture of five grass species widely
      represented in semi-natural meadows of central France. At the end of the second
      growing season, beech seedlings in the presence of grass showed significant
      reductions in diameter and height growth, annual shoot elongation, and stem, root
      and leaf biomass, but an increase in root to shoot biomass ratio. Grasses greatly
      reduced soil water availability, which was positively correlated with daily
      seedling diameter increment. Beech seedlings seemed to respond to water deficit
      by anticipating stomatal closure. There was evidence of competition for nitrogen
      (N) by grasses, but its effect on seedling development could not be separated
      from that of competition for water. By labeling the plants with 15N, we showed
      that beech seedlings absorbed little N when grasses were present, whereas grasses
      took up more than 97% of the total N absorbed in the container. We conclude that,
      even if beech seedlings display morphological and physiological adaptation to
      below ground competition, their development in full-light conditions may be
      strongly restricted by competition from grass species.

PMID- 14652214
TI  - Effects of aluminum on organic acid metabolism and secretion by red spruce cell
      suspension cultures and the reversal of Al effects on growth and polyamine
      metabolism by exogenous organic acids.
AB  - In the absence of added Al, the concentration of succinate in cultured red spruce
      (Picea rubens Sarg.) cells was 15-20 times higher (> 600 nmol g-1FW) than that of
      citrate or oxalate and 4-6 times higher than that of malate. Addition of AlCl3
      (effective monomeric Al concentrations of 0.23 and 0.48 mM) to 3-day-old
      suspension cultures significantly increased cellular succinate concentrations
      with a concomitant decrease in cellular oxalate concentrations. However, in the
      medium of Al-treated cell cultures, both succinate and oxalate concentrations
      were significantly higher than in the medium of cell cultures without added Al,
      and oxalate concentrations were several times higher than succinate
      concentrations. Aluminum did not significantly affect the cellular concentrations
      of malate, ascorbate and citrate, and none of these organic acids was present in
      detectable quantities in the medium. Exogenous succinate alone or with Al had no
      effect on cellular free polyamine concentrations or cell mass. Aluminum caused a
      significant increase in cellular putrescine concentrations. Addition of malate
      had a positive effect on growth and completely reversed the effects of Al on cell
      physiology. In contrast, the addition of oxalate and citrate only partly reversed
      the effects of Al.

PMID- 14652215
TI  - Effectiveness of mycorrhizal inoculation in the nursery on growth and water
      relations of Pinus radiata in different water regimes.
AB  - We compared the performance of mycorrhiza-inoculated and non-inoculated radiata
      pine (Pinus radiata D. Don) seedlings in two field studies. In the first study,
      above ground growth of 2-year-old container-grown trees was compared after
      planting in two areas that differed in water availability. Mycorrhizal
      inoculation significantly improved above ground growth in the 2 years after
      planting in both areas, especially at the drier site. In the second study, the
      influence of Rhizopogon roseolus (Corda ex Sturm) Th. Fries and Scleroderma
      citrinum Pers. on xylem water potential and hydraulic conductance at the soil
      root interface of trees established at the same sites was assessed. Nursery
      inoculations with R. roseolus and S. citrinum improved tree growth during the
      first 2 years after field outplanting, particularly at the drier site.

PMID- 14652216
TI  - Gas exchange and foliage characteristics of two poplar clones grown in soil
      amended with industrial waste.
AB  - Plants can remove or immobilize various environmental contaminants; however,
      little is known about the physiological mechanisms underlying responses to soil
      amendment with biosolids contaminated with heavy metals. We investigated the
      responses of cuttings of hybrid poplar clones Eridano and I-214 grown for a
      season in soil amended with nutrient-rich organic material from tanneries, which
      contains potentially toxic amounts of heavy elements. Plant growth traits, gas
      exchange parameters, stomatal density and leaf layer thickness of frozen-hydrated
      leaves, and foliar concentrations of heavy metals and nitrogen were determined.
      Overall, soil amendment increased net assimilation rate and growth, but the
      cuttings accumulated only small quantities of heavy metal soil contaminants.

PMID- 14652217
TI  - Effects of partial defoliation on carbon and nitrogen partitioning and
      photosynthetic carbon uptake by two-year-old cork oak (Quercus suber) saplings.
AB  - At the end of the growing season in late July, 20-month-old cork oak (Quercus
      suber L.) saplings were partially defoliated (63% of leaf area) to evaluate their
      ability to recover leaf area after defoliation. At 18 and 127 days after
      defoliation, changes in starch and nitrogen pools were determined in leaves and
      perennial organs, and variations in photosynthetic carbon uptake were
      investigated. To determine the role of stored nitrogen in regrowth after
      defoliation, plant nitrogen was labeled in the previous winter by enriching the
      nutrient solution with 15N. Plants recovered the lost leaf area in 127 days.
      Although there was remobilization of starch and nitrogen from leaves and
      perennial organs, the availability of resources for growth in the following
      spring was not decreased by defoliation. On the contrary, starch concentration in
      coarse roots was higher in defoliated saplings than in control saplings,
      presumably as a result of the higher net CO2 exchange rate in newly developed
      leaves compared with pre-existing leaves.

PMID- 14652218
TI  - Nitrogen storage and its interaction with carbohydrates of young apple trees in
      response to nitrogen supply.
AB  - Bench-grafted 'Fuji/M.26' apple (Malus domestica Borkh.) trees received a
      constant nitrogen (N) supply (10.7 mM) from bud break to the end of June, and
      were then fertigated with 0, 5, 10, 15 or 20 mM N in a modified Hoagland's
      solution for 2 months during the summer. In mid-October, half of the trees
      fertigated at each N concentration were sprayed twice with 3% urea, whereas the
      remaining trees served as controls. All trees were harvested after natural leaf
      fall and were stored at 2 degrees C. Five trees from each of the N treatment
      combinations were destructively sampled during dormancy to determine the
      composition of N and total nonstructural carbohydrates (TNC). As the N supply
      from fertigation increased, amounts of N in both free amino acids and proteins
      increased, whereas C/N ratios decreased. Foliar urea applications in the fall
      significantly increased amounts of N in both free amino acids and proteins, but
      decreased their C/N ratios. Arginine, the most abundant amino acid in both free
      amino acids and in proteins, accounted for an increasing proportion of N in free
      amino acids and proteins with increasing N supply from fertigation or foliar urea
      application. The ratio of protein N to free amino acid N decreased from about
      27.1 to 3.2 as N supply from fertigation increased from 0 to 20 mM, and decreased
      further to 3.0 in response to foliar urea applications in the fall.
      Concentrations of glucose, fructose, sucrose and TNC decreased as the N supply
      from fertigation increased, whereas concentrations of sorbitol and starch
      remained relatively unchanged. Foliar urea applications decreased the
      concentration of each TNC component and the TNC concentration in each N
      fertigation treatment. A negative linear relationship was found between carbon in
      TNC and N in proteins and free amino acids. The sum of carbon in TNC, proteins
      and free amino acids remained constant in response to N supply from fertigation.
      However, foliar urea applications decreased the sum of carbon in proteins, free
      amino acids and TNC because about 21% of the decrease in TNC carbon was not
      recovered in free amino acids or proteins. Young apple trees store N and carbon
      dynamically in response to N supply. As N supply increases, an increasing
      proportion of N is found in the form of free amino acids, which have a low carbon
      cost, although proteins remain the main form of N storage. Furthermore, part of
      the carbon from TNC is incorporated into amino acids and proteins, decreasing the
      carbon stored as TNC and increasing the carbon stored as amino acids and
      proteins.

PMID- 14652219
TI  - Winter variation in xylem sap pH of walnut trees: involvement of plasma membrane
      H+-ATPase of vessel-associated cells.
AB  - We studied seasonal variation in xylem sap pH of Juglans regia L. Our main
      objectives were to (1) test the effect of temperature on seasonal changes in
      xylem sap pH and (2) study the involvement of plasma membrane H+-ATPase of vessel
      associated cells in the control of sap pH. For this purpose, orchard-grown trees
      were compared with trees grown in a heated (> or = 15 degrees C) greenhouse.
      During autumn, sap pH was not directly influenced by temperature. A seasonal
      change in H+-ATPase activity resulting from seasonal variation in the amount of
      protein was measured in orchard-grown trees, whereas no significant seasonal
      changes were recorded in greenhouse-grown trees. Our data suggest that H+-ATPase
      does not regulate xylem sap pH directly by donating protons to the xylem, but by
      facilitating secondary active H+/sugar transport, among other mechanisms.

PMID- 14652220
TI  - Drought resistance of Ailanthus altissima: root hydraulics and water relations.
AB  - Drought resistance of Ailanthus altissima (Mill.) Swingle is a major factor
      underlying the impressively wide expansion of this species in Europe and North
      America. We studied the specific mechanism used by A. altissima to withstand
      drought by subjecting potted seedlings to four irrigation regimes. At the end of
      the 13-week treatment period, soil water potential was -0.05 MPa for well-watered
      control seedlings (W) and -0.4, -0.8 and -1.7 MPa for drought-stressed seedlings
      (S) in irrigation regimes S1, S2 and S3, respectively. Root and shoot biomass
      production did not differ significantly among the four groups. A progressively
      marked stomatal closure was observed in drought-stressed seedlings, leading to
      homeostasis of leaf water potential, which was maintained well above the turgor
      loss point. Root and shoot hydraulics were measured with a high-pressure flow
      meter. When scaled by leaf surface area, shoot hydraulic conductance did not
      differ among the treated seedlings, whereas root hydraulic conductance decreased
      by about 20% in S1 and S2 seedlings and by about 70% in S3 seedlings, with
      respect to the well-watered control value. Similar differences were observed when
      root hydraulic conductance was scaled by root surface area, suggesting that roots
      had become less permeable to water. Anatomical observations of root cross
      sections revealed that S3 seedlings had shrunken cortical cells and a multilayer
      endodermal-like tissue that probably impaired soil-to-root stele water transport.
      We conclude that A. altissima seedlings are able to withstand drought by
      employing a highly effective water-saving mechanism that involves reduced water
      loss by leaves and reduced root hydraulic conductance. This water-saving
      mechanism helps explain how A. altissima successfully competes with native
      vegetation.

PMID- 14652221
TI  - Exposure to elevated carbon dioxide concentration in the dark lowers the
      respiration quotient of Vitis cane wood.
AB  - Cane cuttings of the grapevine rootstock Vitis rupestris Scheele x V. riparia
      Michx. cv. 3309 Couderc were brought out of endodormancy by warming at 30 degrees
      C. Cane pieces (12 to 13 cm long) with nodes containing a primary bud were placed
      in a gas exchange system and monitored for net respiratory fluxes of CO2 and O2.
      Grapevine respiration rates expressed on a wood volume basis were 1.4 to 3.4 mmol
      CO2 or O2 m-3s-1, which is higher than stem respiration rates reported for many
      other woody taxa but similar to rates measured for ecodormant buds of other Vitis
      species. Passive water loss from canes was 0.7 to 1.2 mmol H2O m-3s-1. During a 7
      day period, nonstructural carbohydrate concentrations in cane wood declined only
      slightly, whereas sucrose was nearly completely consumed. When ambient CO2
      concentration ([CO2]) was raised from 300 to 750 micro molmol-1 and then 2000
      micromol mol-1, net CO2 exchange rates declined by 5.9 +/- 0.6 and then 11.0 +/-
      0.6%, whereas net O2 consumption rates remained about constant. The mean
      respiration quotient (net CO2/O2 flux) for canes with intact ecodormant buds was
      0.99 +/- 0.03 when the [CO2] was 300 micromol mol-1, and decreased to 0.87 +/-
      0.03 and 0.088 +/- 0.02 when the [CO2] was increased to 750 and 2000 micromol mol
      1, respectively. The results support the hypothesis that, in Vitis canes,
      inhibition of respiratory CO2 efflux in response to high [CO2] is an indirect
      consequence of non-photosynthetic carboxylation reactions, and not a result of
      inhibition of respiratory metabolism.

PMID- 14652222
TI  - Impact of successive drought and re-watering cycles on growth and specific leaf
      area of two Populus x canadensis (Moench) clones, 'Dorskamp' and 'Luisa_Avanzo'.
AB  - Responses to successive drought and re-watering cycles (1-3 cycles) were compared
      in greenhouse-grown cuttings of Populus x canadensis (Moench) clones, 'Luisa_
      Avanzo' and 'Dorskamp.' Total leaf number increment rate, duration of leaf
      expansion, total and individual leaf area expansion rates and stomatal
      conductance were recorded periodically during the experiment. Soil water content
      (SWC) and predawn leaf water potential (Psi(WP)) were measured four times during
      each drought cycle. In parallel, relative leaf water content (RWC) and specific
      leaf area (SLA) were estimated on leaves collected from the top to bottom of each
      cutting. Under well-watered conditions, 'Luisa_Avanzo' and 'Dorskamp' differed in
      their patterns of leaf area expansion. Although duration of leaf expansion was
      similar between clones, 'Luisa_ Avanzo' exhibited higher total leaf number
      increment rates and individual leaf area increases than 'Dorskamp.' As a result,
      'Luisa_Avanzo' cuttings reached larger individual and total leaf areas than
      'Dorskamp.' 'Dorskamp' leaves had lower SLA than 'Luisa_Avanzo' leaves. In
      response to successive drought cycles, both clones underwent decreases in total
      leaf number increment rates and in total leaf area expansion rates, but both
      whole-plant and individual leaf areas were drastically reduced only in
      'Luisa_Avanzo.' 'Dorskamp' maintained a constant leaf area as a result of an
      increase in the duration of leaf expansion during drought and a significant
      stimulation of individual leaf area expansion rate and total leaf number
      increment rate in response to re-watering. Drought caused a greater decrease in
      SLA in 'Luisa_Avanzo' than in 'Dorskamp.' Expanded leaves of 'Dorskamp' were
      constitutively dense or thick, or both, whereas leaves of 'Luisa_Avanzo' became
      dense or thick, or both, only in response to drought. In both clones, re-watering
      caused partial recovery of SLA to control values. Our data confirm previous field
      and greenhouse observations that 'Dorskamp' is more tolerant to successive
      drought and re-watering cycles than 'Luisa_Avanzo.' We conclude that this
      difference is mainly attributable to the plasticity of 'Dorskamp' after re
      watering, rather than to clonal differences in drought responses.

PMID- 14652223
TI  - Freezing tolerance of conifer seeds and germinants.
AB  - Survival after freezing was measured for seeds and germinants of four seedlots
      each of interior spruce (Picea glauca x engelmannii complex), lodgepole pine
      (Pinus contorta Dougl. ex Loud.), Douglas-fir (Pseudotsuga menziesii (Mirb.)
      Franco) and western red cedar (Thuja plicata Donn ex D. Donn). Effects of eight
      seed treatments on post-freezing survival of seeds and germinants were tested:
      dry, imbibed and stratified seed, and seed placed in a growth chamber for 2, 5,
      10, 15, 20 or 30 days in a 16-h photoperiod and a 22/17 degrees C thermoperiod.
      Survival was related to the water content of seeds and germinants, germination
      rate and seedlot origin. After freezing for 3 h at -196 degrees C, dry seed of
      most seedlots of interior spruce, Douglas-fir and western red cedar had 84-96%
      germination, whereas lodgepole pine seedlots had 53-82% germination. Freezing
      tolerance declined significantly after imbibition in lodgepole pine, Douglas-fir
      and interior spruce seed (western red cedar was not tested), and mean LT50 of
      imbibed seed of these species was -30, -24.5 and -20 degrees C, respectively.
      Freezing tolerance continued to decline to a minimum LT50 of -4 to -7 degrees C
      after 10 days in a growth chamber for interior spruce, Douglas-fir and lodgepole
      pine, or after 15 days for western red cedar. Minimum freezing tolerance was
      reached at the stage of rapid hypocotyl elongation. In all species, a slight
      increase in freezing tolerance of germinants was observed once cotyledons emerged
      from the seed coat. The decrease in freezing tolerance during the transition from
      dry to germinating seed correlated with increases in seed water content. Changes
      in freezing tolerance between 10 and 30 days in the growth chamber were not
      correlated with seedling water content. Within a species, seedlots differed
      significantly in freezing tolerance after 2 or 5 days in the growth chamber.
      Because all seedlots of interior spruce and lodgepole pine germinated quickly,
      there was no correlation between seedlot hardiness and rate of germination.
      Germination rate and freezing tolerance of Douglas-fir and western red cedar
      seedlots was negatively correlated. There was a significant correlation between
      LT50 after 10 days in the growth chamber and minimum spring temperature at the
      location of seedlot origin for interior spruce and three seedlots of western red
      cedar, but no relationship was apparent for lodgepole pine and Douglas-fir.

PMID- 14652224
TI  - Developmental stages during the rooting of in-vitro-cultured Quercus robur shoots
      from material of juvenile and mature origin.
AB  - In-vitro-cultured shoots of clones initiated from shoots of the basal parts (BS)
      and the crown (C) of two mature Quercus robur L. trees were subjected to rooting
      experiments to relate rooting with shoot topophysical origin. The BS shoots
      exhibited morphologically juvenile characteristics and rooted more easily after
      indole-3-butyric acid (IBA) treatment than C shoots. When naphthylphthalamic acid
      (NPA) was applied to BS shoots, rooting capacity decreased and root emergence was
      delayed at least 2 days compared with shoots treated with IBA only. During the
      first days of the rooting process, endogenous indole-3-acetic acid (IAA)
      concentration was higher in C shoots than in BS shoots, regardless of whether the
      shoots were treated with NPA. Mitotic figures were observed in cells from the
      basal part of both BS and C shoots 24 h after IBA treatment. After 4 days of IBA
      treatment, the occurrence of histological events differed between BS shoots and C
      shoots. Cells of BS shoots became meristematic, giving rise to meristemoids and
      root primordia, whereas no differentiation of root meristemoids occurred in cells
      of C shoots. Thus, although adult oak material (C shoots) is capable of
      responding to the initial stimulus of auxin during the adventitious rooting
      process, the endogenous IAA concentration is not the factor limiting rooting in
      adult material.

PMID- 14652225
TI  - Influence of leaf angle on photosynthesis and the xanthophyll cycle in the
      tropical tree species Acacia crassicarpa.
AB  - We examined the effects of artificially altering leaf angle of the tropical tree
      species Acacia crassicarpa (A. Cunn. ex Benth., Fabaceae) on light interception,
      leaf temperature and photosynthesis in the wet and dry seasons of tropical
      Australia. Reducing leaf angle from the natural near-vertical angle (90 degrees )
      to 67.5, 45, 22.5 and 0 degrees greatly increased light interception and leaf
      temperature, and decreased photosynthetic activity. Compared with the 90 degrees
      phyllodes, net photosynthetic rates in the horizontal phyllodes decreased by 18
      and 42% by the second day of leaf angle change in the wet and dry seasons,
      respectively. The corresponding values for Day 7 were 46 and 66%. Leaf angle
      reduction also altered the diurnal pattern of photosynthesis (from two peaks to
      one peak) and reduced daily CO2 fixation by 23-50% by Day 2 and by 50-75% by Day
      7 in the dry season. In contrast, the xanthophyll cycle pool size in the
      phyllodes increased with leaf angle reduction. Thus, there are at least five
      major advantages to maintaining high leaf angle orientation in tropical tree
      species. First, it reduces excessive light interception. Second, it lowers leaf
      temperature. Third, it protects the photosynthetic apparatus against photodamage
      by excessive light. Fourth, it minimizes xanthophyll cycle activity and reduces
      the cost for xanthophyll biosynthesis. Finally, it enhances photosynthetic
      activity and helps to sustain high plant productivity.

PMID- 14652226
TI  - Interactive effects of temperature and precipitation on soil respiration in a
      temperate maritime pine forest.
AB  - Soil respiration (SR) was monitored periodically throughout 2001 in a Scots pine
      (Pinus sylvestris L.) stand located in the Belgian Campine region. As expected
      for a temperate maritime forest, temperature was the dominant control over SR
      during most of the year. However, during late spring and summer, when soil water
      content (SWC) was limiting, SR was insensitive to temperature (Q(10) = 1.24). We
      observed that during prolonged rain-free periods, when SWC was less than 15%
      (v/v), SR decreased dramatically (up to 50%) and SWC took over control of SR.
      During such drought periods, however, rain events sometimes stimulated SR and
      restored temperature control over SR, even though SWC in the mineral soil was
      low. We hypothesize that restoration of temperature control occurred only when
      rain events adequately rewetted the uppermost soil layers, where most of the
      respiratory activity occurred. To quantify the rewetting capacity of rain events,
      an index (I(w)) was designed that incorporated rainfall intensity, time elapsed
      since the last rain event, and atmospheric vapor pressure deficit (a proxy for
      evaporative water losses). To simulate SR fluxes, a model was developed that
      included the effects of soil temperature and, under drought and non-rewetting
      conditions (I(w) and SWC < threshold), an SWC response function. The model
      explained 95% of the temporal variability in SR observed during summer, whereas
      the temperature function alone explained only 73% of this variability. Our
      results revealed that, in addition to temperature and SWC, rain plays a role in
      determining the total amount of carbon released from soils, even in a maritime
      climate.

PMID- 14652227
TI  - A hot flash on tamoxifen metabolism.

PMID- 14652228
TI  - Research and public health implications of the intricate relationship between
      calcium and vitamin D in the prevention of colorectal neoplasia.

PMID- 14652229
TI  - Critics question price of success in halted clinical trial of aromatase inhibitor
      letrozole.

PMID- 14652230
TI  - Big plans for small molecules: NIH launches chemical genomics initiative.

PMID- 14652231
TI  - 'Roadmap' gives new direction to trans-NIH research.

PMID- 14652232
TI  - What's All the Buzz? Fruit Flies Provide Unique Model for Cancer Research.

PMID- 14652234
TI  - For investigational targeted drugs, combination trials pose challenges.

PMID- 14652235
TI  - Stat bite: Lifetime risk of being diagnosed with cancer.

PMID- 14652236
TI  - The epigenome as a target for cancer chemoprevention.
AB  - Epigenetic events, a key driving force in the development of cancer, are
      alterations in gene expression without changes in the DNA coding sequence that
      are heritable through cell division. Such changes occur throughout all stages of
      tumorigenesis, including the early phases, and are increasingly recognized as
      major mechanisms involved in silencing tumor suppressor genes. Epigenetic changes
      can be reversed by the use of small molecules and, thus, such changes are
      promising targets for cancer chemopreventive drug development. This review
      examines the basis for targeting the epigenome as a prevention strategy, focusing
      on understanding the epigenetic changes that occur before the development of
      frank malignancy, when chemopreventive intervention will have the maximal impact.

PMID- 14652237
TI  - Active tamoxifen metabolite plasma concentrations after coadministration of
      tamoxifen and the selective serotonin reuptake inhibitor paroxetine.
AB  - BACKGROUND: Tamoxifen, a selective estrogen receptor modulator (SERM), is
      converted to 4-hydroxy-tamoxifen and other active metabolites by cytochrome P450
      (CYP) enzymes. Selective serotonin reuptake inhibitors (SSRIs), which are often
      prescribed to alleviate tamoxifen-associated hot flashes, can inhibit CYPs. In a
      prospective clinical trial, we tested the effects of coadministration of
      tamoxifen and the SSRI paroxetine, an inhibitor of CYP2D6, on tamoxifen
      metabolism. METHODS: Tamoxifen and its metabolites were measured in the plasma of
      12 women of known CYP2D6 genotype with breast cancer who were taking adjuvant
      tamoxifen before and after 4 weeks of coadministered paroxetine. We assessed the
      inhibitory activity of pure tamoxifen metabolites in an estradiol-stimulated MCF7
      cell proliferation assay. To determine which CYP isoforms were involved in the
      metabolism of tamoxifen to specific metabolites, we used CYP isoform-specific
      inhibitors. All statistical tests were two-sided. RESULTS: We separated,
      purified, and identified the metabolite 4-hydroxy-N-desmethyl-tamoxifen, which we
      named endoxifen. Plasma concentrations of endoxifen statistically significantly
      decreased from a mean of 12.4 ng/mL before paroxetine coadministration to 5.5
      ng/mL afterward (difference = 6.9 ng/mL, 95% confidence interval [CI] = 2.7 to
      11.2 ng/mL) (P =.004). Endoxifen concentrations decreased by 64% (95% CI = 39% to
      89%) in women with a wild-type CYP2D6 genotype but by only 24% (95% CI = 23% to
      71%) in women with a variant CYP2D6 genotype (P =.03). Endoxifen and 4-hydroxy
      tamoxifen inhibited estradiol-stimulated MCF7 cell proliferation with equal
      potency. In vitro, troleandomycin, an inhibitor of CYP3A4, inhibited the
      demethylation of tamoxifen to N-desmethyl-tamoxifen by 78% (95% CI = 65% to 91%),
      and quinidine, an inhibitor of CYP2D6, reduced the subsequent hydroxylation of N
      desmethyl-tamoxifen to endoxifen by 79% (95% CI = 50% to 108%). CONCLUSIONS:
      Endoxifen is an active tamoxifen metabolite that is generated via CYP3A4-mediated
      N-demethylation and CYP2D6-mediated hydroxylation. Coadministration of paroxetine
      decreased the plasma concentration of endoxifen. Our data suggest that CYP2D6
      genotype and drug interactions should be considered in women treated with
      tamoxifen.

PMID- 14652238
TI  - Vitamin D, calcium supplementation, and colorectal adenomas: results of a
      randomized trial.
AB  - BACKGROUND: Calcium and vitamin D both appear to have antineoplastic effects in
      the large bowel. Although these nutrients are inter-related metabolically in bone
      and in the normal intestine, their potential interactions in large-bowel
      carcinogenesis are not well understood. METHODS: We assessed independent and
      joint effects of calcium supplementation and vitamin D status on adenoma
      recurrence in 803 subjects in a multi-center, placebo-controlled randomized
      clinical trial of calcium supplementation for the prevention of colorectal
      adenoma recurrence. Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25
      dihydroxy [1,25-(OH)2] vitamin D levels were determined, and the Taq I and Fok I
      polymorphisms in the vitamin D receptor (VDR) gene were analyzed by polymerase
      chain reaction. Risk ratios (RRs) for any adenoma recurrence were computed for
      calcium supplementation within groups defined by serum vitamin D levels and for
      serum vitamin D levels within treatment groups. Associations of VDR polymorphisms
      with recurrence risk were also evaluated. All statistical tests were two-sided.
      RESULTS: Among subjects with baseline 25-(OH) vitamin D levels at or below the
      median (29.1 ng/mL), calcium supplementation was not associated with adenoma
      recurrence, whereas among those with levels above the median, calcium
      supplementation was associated with a reduced risk (RR = 0.71, 95 % confidence
      interval [CI] = 0.57 to 0.89, P for interaction =.012). Conversely, serum 25-(OH)
      vitamin D levels were associated with a reduced risk only among subjects
      receiving calcium supplements (RR per 12 ng/mL increase of vitamin D = 0.88, 95%
      CI = 0.77 to 0.99, P for interaction =.006). VDR polymorphisms were not related
      to adenoma recurrence and did not modify the associations with vitamin D or
      calcium. CONCLUSIONS: Calcium supplementation and vitamin D status appear to act
      largely together, not separately, to reduce the risk of colorectal adenoma
      recurrence. VDR genotype does not appear to be associated with risk.

PMID- 14652239
TI  - Human papillomavirus and oral cancer: the International Agency for Research on
      Cancer multicenter study.
AB  - BACKGROUND: Human papillomavirus (HPV), the causal agent of cervical cancer,
      appears to be involved in the etiology of cancer of the oral cavity and
      oropharynx. To investigate these associations, we conducted a multicenter case
      control study of cancer of the oral cavity and oropharynx in nine countries.
      METHODS: We recruited 1670 case patients (1415 with cancer of the oral cavity and
      255 with cancer of the oropharynx) and 1732 control subjects and obtained an
      interview, oral exfoliated cells, and blood from all participants and fresh
      biopsy specimens from case patients. HPV DNA was detected by polymerase chain
      reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were
      detected with enzyme-linked immunosorbent assays. Multivariable models were used
      for case-control and case-case comparisons. RESULTS: HPV DNA was detected in
      biopsy specimens of 3.9% (95% confidence interval [CI] = 2.5% to 5.3%) of 766
      cancers of the oral cavity with valid PCR results and 18.3% (95% CI = 12.0% to
      24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with
      valid PCR results. HPV DNA in cancer biopsy specimens was detected less
      frequently among tobacco smokers and paan chewers and more frequently among
      subjects who reported more than one sexual partner or who practiced oral sex.
      HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in
      exfoliated cells was not associated with cancer risk or with HPV DNA detection in
      biopsy specimens. Antibodies against HPV16 L1 were associated with risk for
      cancers of the oral cavity (odds ratio [OR] = 1.5, 95% CI = 1.1 to 2.1) and the
      oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7
      were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI =
      1.7 to 4.8) and the oropharynx (OR = 9.2, 95% CI = 4.8 to 17.7). CONCLUSIONS: HPV
      appears to play an etiologic role in many cancers of the oropharynx and possibly
      a small subgroup of cancers of the oral cavity. The most common HPV type in
      genital cancers (HPV16) was also the most common in these tumors. The mechanism
      of transmission of HPV to the oral cavity warrants further investigation.

PMID- 14652240
TI  - Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The relationship between the use of non-steroidal anti-inflammatory
      drugs (NSAIDs), including aspirin, and the risk of gastric cancer has not been
      well studied. We performed a systematic review and meta-analysis of published
      studies to evaluate the association between use of this class of drugs and the
      risk of gastric cancer. METHODS: A fully recursive literature search to January
      2003 was conducted in MEDLINE, PubMed, and CANCERLIT to identify potentially
      relevant case-control or cohort studies. Summary odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated under a random-effects model. RESULTS:
      Nine studies (eight case-control and one cohort) with a total of 2831 gastric
      cancer case patients were identified. NSAID use was associated with a reduced
      risk of gastric cancer, with a summary odds ratio of 0.78 (95% CI = 0.69 to
      0.87). Users of aspirin (OR = 0.73, 95% CI = 0.63 to 0.86) and non-aspirin NSAIDs
      (OR = 0.74, 95% CI = 0.55 to 1.00) experienced similar magnitudes of risk
      reduction. Regular users of NSAIDs (OR = 0.57, 95% CI = 0.44 to 0.74) experienced
      a lower risk of gastric cancer relative to nonusers than did irregular users (OR
      = 0.76, 95% CI = 0.62 to 0.94; P =.09 versus regular users). A stratified
      analysis showed that NSAID use was associated with a statistically significant
      reduction in risk of noncardia gastric cancer (OR = 0.72, 95% CI = 0.58 to 0.89),
      but not of gastric cancer at the cardia (OR = 0.80, 95% CI = 0.53 to 1.20). There
      was no evidence that study design or type of control subject substantially
      influenced the estimate of effects. CONCLUSION: NSAID use was associated with a
      decreased risk of gastric cancer in a dose-dependent manner. This finding
      warrants proper clinical trials in populations with high risk of gastric cancer.

PMID- 14652241
TI  - Prostate-specific antigen screening in elderly men.
AB  - Although the efficacy of prostate-specific antigen (PSA) screening for prostate
      cancer has not been established, it is widely used. However, despite the overall
      controversy regarding PSA screening, there has been general agreement that
      elderly men (i.e., those aged 75 years or older) should not be screened. By using
      a nationally representative sample of 7889 men who participated in the 2000
      National Health Interview Survey, we found that the rate of PSA screening among
      men aged 75 or older was 32.5% (95% confidence interval [CI] = 28.8% to 36.1%),
      which was greater than that of fecal occult blood screening among men of the same
      age (22.8%, 95% CI = 19.2% to 26.4%) and was comparable with that of annual Pap
      smear screening among women aged 75 years or older (29.0%, 95% CI = 26.6% to
      31.3%). Among screened elderly men, 88.4% (95% CI = 82.3% to 92.6%) reported that
      their doctor first suggested screening and 66.5% (95% CI = 59.7% to 73.3%)
      reported that the risks and benefits of screening were discussed before
      screening. We conclude that strategies are needed to increase understanding of
      the risks and benefits of PSA screening among elderly men.

PMID- 14652242
TI  - Cancer incidence in patients with type 1 diabetes mellitus: a population-based
      cohort study in Sweden.
AB  - Although patients with type 2 diabetes have elevated risks of liver, pancreatic,
      kidney, and endometrial cancer, little is known about the risk of cancer for
      patients with type 1 diabetes. We conducted a cohort study to examine cancer
      incidence among 29 187 patients in Sweden who were hospitalized for type 1
      diabetes from 1965 through 1999. Relative risks of cancer were estimated by age-,
      sex- and calendar year of follow-up--adjusted standardized incidence ratios
      (SIRs), using data for the entire Swedish population as a reference. After
      excluding cancers diagnosed during the first year after hospital discharge, we
      observed 355 incident cases of cancer, which corresponded to a 20% increase in
      overall cancer incidence among type 1 diabetes patients (SIR = 1.2, 95%
      confidence interval [CI] = 1.0 to 1.3). Patients with type 1 diabetes had
      elevated risks of cancers of the stomach (SIR = 2.3, 95% CI = 1.1 to 4.1), cervix
      (SIR = 1.6, 95% CI = 1.1 to 2.2), and endometrium (SIR = 2.7, 95% CI = 1.4 to
      4.7). Type 1 diabetes is associated with a modest excess cancer risk overall and
      risks of specific cancers that differ from those associated with type 2 diabetes.

PMID- 14652244
TI  - Re: Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous
      melanoma.

PMID- 14652247
TI  - Medical nemesis. 1974.
AB  - This article was originally published in the Lancet in 1974.( dagger ) It is
      reprinted here, as the centre of a set of articles, in memory of the death of
      Ivan Illich in December 2002.

PMID- 14652248
TI  - Ivan Illich.

PMID- 14652249
TI  - Harriet L Hardy, MD: fighting man-made disease.

PMID- 14652250
TI  - Ivan Illich. He lived his own testimony.

PMID- 14652251
TI  - Nemesis, Sisyphus, and a contribution from the medical humanities to health
      research.

PMID- 14652252
TI  - Ivan Illich and medical nemesis.

PMID- 14652253
TI  - Limits to medicine. Medical nemesis: the expropriation of health.

PMID- 14652255
TI  - Less medicine, more health: a memoir of Ivan Illich.

PMID- 14652254
TI  - Economics, demography, and epidemiology: an interdisciplinary glossary.
AB  - This glossary focuses on the "borderland" between demography, economic history,
      economic theory, and epidemiology

PMID- 14652256
TI  - Why are women underused in the JECH peer review process?

PMID- 14652257
TI  - User requirements and understanding of public health networks in England.
AB  - BACKGROUND: The movement of public health professionals from health authorities
      to primary care trusts has increased their isolation and dependence on public
      health networks for communication. METHODS: A cross sectional survey of 60 public
      health professionals working in England was performed to determine their
      understanding of the term "public health network" and to explore the functions
      that they would like these networks to perform. It also assessed their attitudes
      towards a national network and towards individual, local, and national web sites
      to support these networks. RESULTS: The most popular functions were the support
      of CPD/education, the identification of expertise and maximisation of scarce
      resources, information sharing, and efficient information/knowledge management.
      The local and national networks and their web sites should provide information on
      current projects of the network and searches to identify people, expertise, and
      reports. CONCLUSION: Public health professionals have a similar but broader
      understanding of the term "public health network" than that of the government
      with greater emphasis on sharing of information. The network is more likely to be
      successful if its priorities are maximising scarce resources, identification of
      expertise, CPD/education, and knowledge management.

PMID- 14652258
TI  - How would schools step up public health measures to control spread of SARS?
AB  - The severe acute respiratory syndrome (SARS) is a rapidly progressive, and
      sometime fatal disease with more than 1800 patients in over a dozen countries in
      Asia, Europe, and North America (including the United States and Canada) within
      two months. On 12 March 2003, the World Health Organisation (WHO) issued a global
      alert about SARS so it became a global challenge. Strengthening the public health
      measures at schools would protect children as well as providing the students an
      opportunity to learn about infectious disease control through life event
      approach. The public health measures at schools include two important components:
      basic understanding of the disease so schools would put on high alert on caution
      cases, and the measures to improve environmental hygiene at schools and
      preventive measures to stop infectious disease transmission. This will help to
      empower the whole community the readiness to deal with other outbreaks in the
      future.

PMID- 14652259
TI  - Tai Po Shun Tak Wong Kin Sheung Memorial School AM, Hong Kong.

PMID- 14652260
TI  - How willing are parents to improve pedestrian safety in their community?
AB  - STUDY OBJECTIVE: To determine how likely parents would be to contribute to
      strategies to reduce pedestrian injury risks and how much they valued such
      interventions. DESIGN: A single referendum willingness to pay survey. Each parent
      was randomised to respond to one of five requested contributions towards each of
      the following activities: constructing speed bumps, volunteering as a crossing
      guard, attending a neighbourhood meeting, or attending a safety workshop.
      SETTING: Community survey. PARTICIPANTS: A sample of 723 Baltimore parents from
      four neighbourhoods stratified by income and child pedestrian injury risk.
      Eligible parents had a child enrolled in one of four elementary schools in
      Baltimore City in May 2001. MAIN RESULTS: The more parents were asked to
      contribute, the less likely they were to do so. Parents were more likely to
      contribute in neighbourhoods with higher ratings of solidarity. The median
      willingness to pay money for speed bumps was conservatively estimated at $6.43.
      The median willingness to contribute time was 2.5 hours for attending workshops,
      2.8 hours in community discussion groups, and 30 hours as a volunteer crossing
      guard. CONCLUSIONS: Parents place a high value on physical and social
      interventions to improve child pedestrian safety.

PMID- 14652261
TI  - Community level risk factors for numbers of landmine victims in Chad and
      Thailand.
AB  - STUDY OBJECTIVE: To determine commonalities of landmine victim risk factors in
      two very different countries. DESIGN AND SETTING: Data on 249 communities in Chad
      and 530 in Thailand were collected during 2000-2001 as part of the Global
      Landmine Survey. Community level variables were analysed in a series of Poisson
      mixture models with number of landmine victims as the dependent variable. Models
      developed for each country were tested on the other to investigate similarities
      and robustness of identification of risk factors. MAIN RESULTS: Increased
      community level risk was associated with population size, closeness to another
      community with victims, emplacement in the previous two years, blocked water or
      pasture, and the proximity of unexploded ordnance or anti-tank mines. In Chad,
      risk factors tended to be more related to identifying communities that had
      crossed a threshold between near zero and moderate risk; Thailand, factors were
      more related to increases in victim rates. CONCLUSIONS: Current systems of
      collecting data on community characteristics and landmine victims can provide
      meaningful risk factor information. Remediation approaches that focus on blockage
      of important resources and areas of recent, high intensity conflicts may be the
      most beneficial in reducing the numbers of victims.

PMID- 14652262
TI  - Self ratings of health predict functional outcome and recurrence free survival
      after stroke.
AB  - STUDY OBJECTIVE: To measure stroke victims' self rated health (SRH) status and
      SRH transition, and to compare how the two are prospectively associated with
      disability and recurrence free survival. DESIGN: Prospective case registry study
      with face to face follow up interviews at three months, one, two, and three
      years. Ascertained were SRH status and SRH transition using single question
      assessments, Barthel Index (BI), Frenchay Activities Index (FAI), and Mini Mental
      State Examination (MMSE). SETTING: A multiethnic inner city population of 234
      533. PARTICIPANTS: Patients surviving the initial three months after a first in a
      lifetime stroke in 1995 to 1998. RESULTS: Of 690 stroke survivors 561 (81.3%)
      could complete the self report items. Answers to the item on SRH status did not
      vary significantly between the four follow up interviews. However, responses to
      the item on SRH transition changed significantly during follow up with three
      months ratings being more negative than all subsequent ratings. SRH transition,
      but not SRH status, showed a prospective association with long term outcome in
      multivariate analyses controlling for the BI, FAI, and MMSE. Compared with all
      other patients, patients reporting "Much worse health" at three months were more
      likely to be disabled ( = BI<20) at one year (OR 6.29, 95% CI 2.26 to 17.52) and
      their combined risk of stroke recurrence and death was increased over five years
      (HR 1.72, 95% CI 1.25 to 2.38). CONCLUSIONS: Items on SRH should be used with
      caution in populations with high rates of disability and language problems, as
      many participants are unable to complete them. SRH transition may be a better
      predictor of disability and recurrence free survival after major medical events
      than SRH status.

PMID- 14652263
TI  - Sex ratio at birth among Chinese babies born in Italy is lower than in China.

PMID- 14652264
TI  - Combination of low birth weight and high adult body mass index: at what age is it
      established and what are its determinants?
AB  - OBJECTIVE: To investigate growth trajectories and predictive factors for those
      with low birth weight and high adult BMI. DESIGN: Birth cohort study. SETTING:
      England, Scotland, and Wales. PARTICIPANTS: All born 3-9 March, 1958. MAIN
      OUTCOME MEASURES: People at "high risk" of adult disease were defined as having a
      combination of lower birth weight (in the lowest third of the distribution) and
      high BMI (in the highest third of the distribution at age 33). RESULTS: 284 of
      3462 men and 338 of 3555 women were identified as "high risk". This group was
      shorter than other cohort members at age 7, on average by 1.2 cm (boys) and 1.8
      cm (girls), with a deficit of about 3 cm in adult height. The "high risk" group
      had a similar mean weight to other subjects at age 7, but were heavier thereafter
      through to age 23. BMI was increased at all ages in the "high risk" group.
      Independent predictors include paternal BMI, maternal height and smoking in
      pregnancy, and social class. For each SD increase in father's BMI the odds of low
      birth weight/high BMI increased by about 20%. For maternal height, a 1 cm
      increase reduced the odds of low birth weight/high BMI by about 5%. Increased ORs
      for "high risk" were found for those with manual social origins (1.61 for men;
      1.49 for women) and for maternal smoking in pregnancy (1.79 and 2.27
      respectively). CONCLUSIONS: Maternal short stature, low social class, and smoking
      during pregnancy influence the development of "high risk" for adult chronic
      disease. The causes of high risk therefore seem to reside in utero and even
      earlier, in the mother's lifetime, with adverse conditions having a detrimental
      affect and favourable conditions protecting against high risk.

PMID- 14652265
TI  - Gender differences in socioeconomic inequality in mortality.
AB  - OBJECTIVES: There is uncertainty about whether position in a socioeconomic
      hierarchy confers different mortality risks on men and women. The objective of
      this study was to conduct a systematic review of gender differences in
      socioeconomic inequality in risk of death. METHODS: This research systematically
      reviewed observational cohort studies describing all cause or cause specific
      mortality for populations aged 25-64 in developed countries. For inclusion in the
      review, mortality had to be reported stratified by gender and by one or more
      measures of socioeconomic status. For all eligible studies, five absolute and six
      relative measures of the socioeconomic inequality in mortality were computed for
      male and female populations separately. RESULTS: A total of 136 published papers
      were reviewed for eligibility, with 58 studies deemed eligible for inclusion. Of
      these eligible studies, 20 papers published data that permitted the computation
      of both absolute and relative measures of inequality. Absolute measures of
      socioeconomic mortality inequality for men and women generally agreed, with about
      90% of studies indicating that male mortality was more unequal than female
      mortality across socioeconomic groups. In contrast, the pattern of relative
      inequality results across the 20 studies suggested that male and female
      socioeconomic inequality in mortality was equivalent. CONCLUSIONS: Inferences
      about gender differences in socioeconomic inequality in mortality are sensitive
      to the choice of inequality measure. Wider understanding of this methodological
      issue would improve the clarity of the reporting and synthesis of evidence on the
      magnitude of health inequalities in populations.

PMID- 14652266
TI  - What underlies the high alcohol related mortality of the disadvantaged: high
      morbidity or poor survival?
AB  - STUDY OBJECTIVE: To investigate whether the large socioeconomic differences in
      alcohol related mortality can be explained by differences in morbidity or
      differences in survival. DESIGN: Register linkage study. A nationwide hospital
      discharge register was linked to population censuses for socioeconomic data and
      to the cause of death register for mortality follow up. SETTING: Finland.
      PARTICIPANTS: Men and women aged 15 years and older discharged from hospitals
      with an alcohol related diagnosis in 1991-1996. MEASUREMENTS: Mortality hazard up
      to the end of 1997 by socioeconomic category was estimated with Cox's regression
      model. MAIN RESULTS: Socioeconomic differences in alcohol related hospitalisation
      rates were almost as large as those that have been observed for alcohol related
      mortality. For example, the rate ratio among male unspecialized workers for any
      alcohol related hospitalisations was 3.6 as compared with upper white collar
      workers; among women the rate ratio was 2.7. Depending on gender, age,
      hospitalisation diagnosis, and cause of death, survival after discharge either
      showed no socioeconomic differences or it was worse among better off groups.
      CONCLUSIONS: The study suggests that differences in survival after
      hospitalisation do not cause the high socioeconomic differences in alcohol
      related mortality.

PMID- 14652267
TI  - Neighbourhood composition and depressive symptoms among older Mexican Americans.
AB  - STUDY OBJECTIVE: Research suggests that economically disadvantaged neighbourhoods
      confer an increased risk of depression to their residents. Little research has
      been reported about the association between ethnic group concentration and
      depression. This study investigated the association between neighbourhood poverty
      and neighbourhood percentage Mexican American and depressive symptoms for older
      Mexican Americans in the south western United States. DESIGN: A population based
      study of older non-institutionalised Mexican Americans from the baseline
      assessment (1993/94) of the Hispanic established population for the epidemiologic
      study of the elderly (H-EPESE) merged with 1990 census data. SETTING: Five south
      western states in the United States. PARTICIPANTS: 3050 Mexican Americans aged 65
      years or older. MAIN RESULTS: There was a strong correlation between the
      percentage of neighbourhood residents living in poverty and the percentage who
      were Mexican American (r = 0.62; p<0.001). Percentage neighbourhood poverty and
      percentage Mexican American had significant and opposite effects on level of
      depressive symptoms among older Mexican Americans. After adjusting for
      demographic and other individual level factors, each 10% increase in
      neighbourhood population in poverty was associated with a 0.763 (95% CI 0.06 to
      1.47) increase in CES-D score, while each 10% increase in Mexican American
      neighbourhood population was associated with a -0.548 (95% CI -0.96 to -0.13)
      unit decrease in CES-D score among older Mexican Americans residing in their
      neighbourhoods. CONCLUSIONS: The findings suggest a sociocultural advantage
      conferred by high density Mexican American neighbourhoods, and suggest the need
      to include community level factors along with individual level factors in
      community based epidemiological health studies.

PMID- 14652268
TI  - Divorce and suicide risk.

PMID- 14652270
TI  - Smoking progression and physical activity.
AB  - This study examined the relationship between changes in physical activity and
      changes in smoking among adolescents. We prospectively examined smoking
      progression, physical activity, demographic factors, and covariates in 978 high
      school students participating in a longitudinal cohort study of the predictors of
      smoking adoption. We used latent growth modeling with the parallel processes
      smoking progression and physical activity as our method, with smoking progression
      measured as an ordered categorical variable. Results indicated that higher levels
      of physical activity reduced the odds of progressing to smoking or a higher level
      of smoking by nearly 1.5 (1.44; P < 0.05). No race differences were found.
      However, being male increased the odds of smoking progression by 1.32 (P < 0.05).
      Higher levels of physical activity may reduce the risk of smoking during
      adolescence. Youth smoking prevention initiatives should incorporate strategies
      to promote physical activity to prevent smoking experimentation and escalation.

PMID- 14652271
TI  - Dietary factors and microsatellite instability in sporadic colon carcinomas.
AB  - Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon
      carcinomas and appears to be primarily due to alterations in hMLH1 and hMSH2.
      Little is known about the role of diet in MSI-related colon carcinogenesis. We
      used data from a Dutch population-based case-control study on sporadic colon
      carcinomas (184 cases and 259 controls) to evaluate associations between dietary
      factors previously reported as being associated with colon cancer risk and MSI,
      hMLH1 expression, and hMLH1 hypermethylation. Red meat intake was significantly
      differently related to microsatellite instability-high (MSI-H) tumors compared
      with microsatellite instability-low/microsatellite stable (MSI-L/MSS) [odds ratio
      (OR), 0.3; 95% confidence interval (CI), 0.1-0.9]. It was inversely associated
      with MSI-H tumors when compared with the population-based controls (OR, 0.5; 95%
      CI, 0.2-1.2) and positively associated with MSI-L/MSS tumors (OR, 1.5; 95% CI,
      0.9-2.6). A positive association was observed for alcohol intake with MSI-H
      tumors (OR, 1.9; 95% CI, 0.8-4.7). Fruit consumption seemed to especially
      decrease the risk of MSI-H tumors with hypermethylated hMLH1 (Methyl(+) tumors)
      [Methyl(+) versus controls: OR = 0.4 and 95% CI = 0.2-0.9; MSI-H tumors without
      hypermethylated hMLH1 (Methyl(-) tumors) versus controls, OR = 1.2 and 95% CI =
      0.8-1.7; Methyl(+) versus Methyl(-) tumors, OR = 0.2 and 95% CI = 0.1-0.9]. Most
      other evaluated dietary factors were not distinctively associated with a specific
      MSI or hMLH1 methylation status. Our data suggest that red meat consumption may
      enhance the development of MSI-L/MSS carcinomas in particular, whereas alcohol
      intake appears to increase the risk of MSI-H tumors. Fruit consumption may
      especially decrease the risk of MSI-H carcinomas exhibiting epigenetically
      silenced hMLH1.

PMID- 14652272
TI  - Familial risks in nervous system tumors.
AB  - We used the nationwide Swedish Family-Cancer Database to analyze the risk for
      nervous system tumors in offspring through parental and sibling probands. Among 0
      68-year-old offspring, close to 11000 patients with a nervous system tumor were
      identified in years 1961 to 2000, among whom 199 had a parent diagnosed with a
      nervous system tumor. Brain tumors constituted 86% of all tumors, and astrocytoma
      was the main histological type, representing half of all cases. Standardized
      incidence ratios (SIRs) for familial risk were only increased for brain tumors of
      meningioma, astrocytoma, and hemangioblastoma histology. When parents were
      diagnosed with tumors of the same histology, the SIRs for offspring were 3.06,
      2.19, and 165 for meningioma, astrocytoma, and hemangioblastoma, respectively.
      Among siblings, the SIRs were 4.41, 3.20, and 61. Age-specific analysis of
      familial astrocytoma revealed three distinct components, one < 10 years, the
      second approximately age 30 years, and the third at age >60 years. The kappa test
      was used to assess the likelihood of an identical histology in two family
      members. The occurrence of hemangioblastoma was completely determined among the
      siblings, and the kappa value was 1.00. Meningiomas were also moderately ordered
      among the siblings, but astrocytomas were less determined. Many syndromes are
      known in which nervous system tumors are manifestations, including
      hemangioblastoma, recognized as part of von Hippel-Lindau disease. Yet, it is
      likely that many brain astrocytoma, meningioma, and mixed families represent yet
      unknown heritable conditions.

PMID- 14652273
TI  - Lifetime physical activity and breast cancer risk in a multiethnic population:
      the San Francisco Bay area breast cancer study.
AB  - Considerable epidemiological data have accumulated in support of a lower risk of
      breast cancer among physically active women. Few studies, however, have examined
      the relation with lifetime physical activity from all sources, and moderate
      activity in particular. We conducted a population-based case-control study of
      breast cancer in Latinas, African Americans, and whites aged 35-79 years to
      assess the association with lifetime histories of moderate and vigorous physical
      activity, including recreational activity, walking, bicycling, household and
      outdoor chores, and occupation. Patients diagnosed with invasive breast cancer
      between 1995 and 1998 were identified through the cancer registry in the San
      Francisco Bay area, and a random sample of women without breast cancer was
      identified through random-digit dialing. A structured questionnaire administered
      in-person was completed by 403 premenopausal cases and 483 controls and 847
      postmenopausal cases and 1065 controls. Summing activities from all sources over
      an individual's lifetime, we found reduced breast cancer risk in both pre- and
      postmenopausal women with the highest versus lowest tertile of average lifetime
      activity (premenopausal: multivariate adjusted odds ratio = 0.74, 95% confidence
      interval = 0.52-1.05; postmenopausal: odds ratio = 0.81, 95% confidence interval
      = 0.64-1.02), with similar reductions in the three racial/ethnic groups. In
      premenopausal women, risk reductions were similar for different types of
      activities, whereas in postmenopausal women, they were limited to occupational
      activity. Considering the intensity of activities, risk reductions were similar
      for moderate and vigorous activities. Because few of the currently known risk
      factors for breast cancer are modifiable, these results underline the public
      health importance of promoting physically active lifestyles.

PMID- 14652274
TI  - Premenopausal dietary carbohydrate, glycemic index, glycemic load, and fiber in
      relation to risk of breast cancer.
AB  - Carbohydrate intake, glycemic index, and glycemic load have been hypothesized to
      increase risk of breast cancer by raising insulin levels, but these associations
      have not been studied extensively. The insulin response to dietary carbohydrate
      is substantially greater among overweight women than among leaner women. Although
      fiber intake has been hypothesized to reduce the risk of breast cancer, data from
      early adult life are lacking. We examined dietary carbohydrate, glycemic index,
      glycemic load, and fiber in relation to breast cancer risk among 90655
      premenopausal women in the Nurses' Health Study II aged 26-46 years in 1991. Diet
      was assessed with a food frequency questionnaire in 1991 and 1995. During 8 years
      of follow-up, we documented 714 incident cases of invasive breast cancer. Dietary
      carbohydrate intake, glycemic load, and glycemic index were not related to breast
      cancer risk in the overall cohort. However, the associations differed by body
      mass index (BMI): among women with BMI < 25 kg/m(2), the multivariate relative
      risks for the increasing quintiles of carbohydrate intake were 1.00 (referent),
      0.87, 0.77, 0.66, and 0.62 [95% confidence interval, 0.40-0.97; P, test for trend
      = 0.02]; and among women with BMI >or=25 kg/m(2), the corresponding relative
      risks were 1.00 (referent), 1.30, 1.35, 1.50, and 1.47 (95% confidence interval,
      0.84-2.59; P, test for trend = 0.14; P, test for interaction = 0.02). Similar
      interaction with BMI was observed for glycemic load, but not for glycemic index.
      Intakes of total fiber and different types of fiber were not appreciably related
      to breast cancer risk. Our findings suggest that the associations between
      carbohydrate intake or glycemic load and breast cancer risk among young adult
      women differ by body weight. Our data do not support a strong association between
      fiber intake and breast cancer risk.

PMID- 14652275
TI  - Adolescent diet and incidence of proliferative benign breast disease.
AB  - Studies of adult diet and risk of breast cancer have yielded mainly null results,
      but this does not rule out a possible impact of adolescent diet. This study
      examined associations between components of adolescent diet and risk of
      proliferative benign breast disease (BBD), a marker for breast cancer. The study
      population consisted of 29494 women in the Nurses' Health Study II who completed
      a questionnaire on adolescent diet in 1998 and who were 33-53 years of age at
      that time. A total of 470 new cases of proliferative BBD were identified between
      1991 and 1997. Incidence rate ratios (RRs) and 95% confidence intervals (CIs)
      were calculated for quartiles of energy-adjusted intakes, using the lowest
      quartile of each as the reference group. Total fat intake during adolescence was
      unrelated to risk of proliferative BBD, although there were positive associations
      for intakes of animal fat and monounsaturated fat and an inverse association for
      intake of vegetable fat. For vitamin E intake, the multivariate RRs were 1.13,
      0.88, and 0.79 (95% CI, 0.61-1.04) for women in the second, third, and highest
      quartiles, respectively (P for trend = 0.05). The multivariate RRs were 0.94,
      0.99, and 0.75 (95% CI, 0.57-0.98) for women in increasing quartiles of fiber
      intake (P for trend = 0.05). Vegetable fat, vitamin E, and fiber intakes during
      adolescence were inversely associated with risk of proliferative BBD in this
      population. Confirmation of these associations may suggest a means for prevention
      of breast cancer.

PMID- 14652276
TI  - Polymorphisms in the DNA repair gene XRCC1, breast cancer risk, and response to
      radiotherapy.
AB  - The study goal was to examine the association of three polymorphisms in the XRCC1
      gene (Arg194Trp, Arg280His, and Arg399Gln) involved in repairing DNA damage
      produced by ionizing radiation, a known breast cancer (BC) risk factor, with BC
      incidence and the possibility of developing an adverse radiotherapy response.
      Genomic DNA from 254 BC cases, 70 of whom were adverse radiotherapy responders
      [radiation-sensitive breast cancer (RS-BC) patients], and 312 female blood donors
      were genotyped using either TaqMan technology or variant specific restriction
      enzyme digestion. Neither the exon 6 codon 194Trp allele [BC versus controls:
      odds ratio (OR), 1.03; 95% confidence interval (CI) 0.62-1.67] nor the exon 10
      codon 399Gln allele (BC versus controls: OR, 0.95; 95% CI, 0.74-1.23) alone was
      associated with an increased BC risk. The exon 9 codon 280His allele was
      associated with an increased risk (OR, 1.8; 95% CI, 1.07-3.05) in both the
      radiation-sensitive and non-radiation-sensitive cases and, in combination with
      the 399Gln allele, was found more frequently in cases than in controls (OR, 2.54;
      95% CI, 1.04-6.22). The exon 6 194Trp allele was associated with the risk of
      developing an adverse response to radiotherapy (RS-BC versus non-radiation
      sensitive BC: OR, 1.98; 95% CI, 0.92-4.17). This allele, in combination with the
      399Gln allele, was found more frequently in RS-BC cases than in the non-radiation
      sensitive BC cases (OR, 4.33; 95% CI, 1.24-15.12). Distinct combinations of XRCC1
      polymorphisms appear to be associated with either an increased BC risk or the
      possibility of developing an adverse radiotherapy response seen in some BC
      patients.

PMID- 14652277
TI  - Association of regimens of hormone replacement therapy to prognostic factors
      among women diagnosed with breast cancer aged 50-64 years.
AB  - This study was conducted to assess the histopathological features of breast
      cancers in women diagnosed with breast cancer at 50-64 years of age who have and
      have not used hormone replacement therapy (HRT). A case-case analysis of the
      tumors from women aged 50-64 years who participated in a multicenter population
      based case-control study of invasive breast cancer was conducted. In-person
      interviews collected a detailed history of all episodes of hormone use.
      Information was collected on selected tumor characteristics from 2346 women with
      breast cancer. Polytomous logistic regression was used to calculate the odds
      ratios (ORs) and 95% confidence intervals (CIs), contrasting the
      histopathological characteristics of the tumors of women who used various
      regimens of HRT with those of women who have never used HRT. The tumors of cases
      who used each regimen of HRT were smaller and of earlier stage than those of non
      HRT users. Adjustment for screening diminished the magnitude of the effect, and
      only cases who used estrogen alone (estrogen replacement therapy) had reduced
      odds of being diagnosed with later-stage disease (regional or distant) than cases
      who never used HRT (OR, 0.7; 95% CI, 0.6-0.9). Higher proportions of estrogen
      receptor (ER)- and progesterone receptor (PR)-positive tumors were seen in cases
      who used any regimen of HRT versus those who did not use HRT. However, after
      adjustment for age and race, only the tumors of cases who used continuous
      combined HRT remained more likely to be ER+ and PR+ [OR ER- = 0.6 (95% CI, 0.4
      0.9) and OR PR- = 0.5 (95% CI, 0.4-0.7)]. The tumors of women with breast cancer
      who used HRT have some better prognostic factors than those of women who have not
      used HRT. However, with the exception of the results noted above, this advantage
      may be due to the racial and age differences in those who use the various
      regimens of HRT and the effect of more frequent screening among HRT users,
      leading to earlier diagnosis.

PMID- 14652278
TI  - Validity of women's self-reports of cancer screening test utilization in a
      managed care population.
AB  - This study was undertaken to examine the validity of self-reported data on breast
      and cervical cancer screening behavior. An abbreviated version of the Behavioral
      Risk Factor Surveillance System telephone survey, including questions on
      mammography, clinical breast examination (CBE), and Papanicolaou test
      utilization, was administered to a sample of 480 women aged 40-74 years, enrolled
      in Kaiser Permanente Colorado for at least 5 years. Screening information
      reported in the telephone interview was compared with that abstracted from
      respondents' medical records. The vast majority of women had a mammogram, CBE,
      and Pap test according to both self-report and medical record. Sensitivity for
      determining whether her last test was within 2 years (3 years for Pap test)
      exceeded 95% for all, whereas specificities were <55%. The percentage of overall
      agreement between self-reported and recorded information was 88.4% (kappa = 0.62)
      for mammography, 87.9% (kappa = 0.45) for CBE, and 87.2% (kappa = 0.54) for Pap
      test. Pearson correlations between self-reported and recorded information for
      specific time interval since most recent mammogram, CBE, and Pap test were 0.72,
      0.58, and 0.65, respectively. Correlation increased greatly when time interval
      was allowed to vary by +/-1 year. In most cases of disagreement, the self-report
      underestimated the time since last screening. These results suggest that self
      reporting of breast and cervical cancer screening is fairly accurate in this
      managed care population, although women tend to underestimate the time since
      their last screening.

PMID- 14652279
TI  - A prospective study of plasma total cysteine and risk of breast cancer.
AB  - Cysteine is the precursor of glutathione, a powerful intracellular antioxidant
      and an important detoxifying agent of carcinogens. However, data relating plasma
      total cysteine to breast cancer risk are sparse. We conducted a prospective
      nested case-control study among 32826 women in the Nurses' Health Study who
      provided blood specimens during 1989-1990. Through 1996, a total of 712 incident
      breast cancer cases were identified and individually matched to 712 controls by
      year of birth, time of day that blood was drawn, fasting status, month of blood
      sampling, recent use of postmenopausal hormones at the time of blood collection,
      and menopausal status. Conditional logistic regression with adjustment for other
      risk factors for breast cancer was used to estimate the relative risks and 95%
      confidence intervals of breast cancer by levels of plasma total cysteine. Higher
      plasma total cysteine concentrations were significantly associated with a lower
      risk of breast cancer. For women in the highest quintile of plasma total
      cysteine, compared with those in the lowest quintile, the multivariate relative
      risk was 0.44 (95% confidence interval, 0.26-0.74). This association was dose
      dependent (P for trend = 0.002) and independent of plasma measures of folate,
      vitamin B(6), vitamin B(12), and total homocysteine. The inverse association
      between plasma total cysteine concentrations and risk of breast cancer was not
      significantly modified by other risk factors for breast cancer, except that a
      stronger association was observed among women who were leaner. The findings from
      this prospective study suggest that higher plasma concentrations of total
      cysteine predict a reduced risk of breast cancer. Cysteine or its precursors
      might have the potential to be chemopreventive against breast cancer.

PMID- 14652280
TI  - The V89L polymorphism in the 5-alpha-reductase type 2 gene and risk of breast
      cancer.
AB  - Women with high androgen levels appear to be at increased risk for breast cancer.
      The 5-alpha-reductase type 2 enzyme (SRD5A2) is an important mediator of local
      androgen actions. The SRD5A2 gene contains a polymorphism leading to a valine to
      leucine change in codon 89 (V89L). The Leu allele has been associated with lower
      SRD5A2 activity and might be protective for breast cancer. At the same time,
      among breast cancer patients, the Leu allele has been associated with lower
      prostate-specific antigen expression, indicating poor prognosis. Within a cohort
      of breast cancer screening participants in the Netherlands (DOM-cohort) we
      examined whether the V89L polymorphism is associated with the risk and prognosis
      of breast cancer. We studied 295 postmenopausal breast cancer cases and a
      randomly selected reference group from the baseline cohort (n = 382). The
      genotype distribution in the reference group was: VV 52%; VL 40%; and LL 8%.
      Compared with women with the VV genotype, adjusted breast cancer rate ratios for
      women with VL and LL genotypes were 1.5 (95% confidence interval = 1.0-2.2) and
      1.1 (95% confidence interval = 0.5-2.1), respectively. Compared with breast
      cancer patients with VV or VL genotypes, those with the LL genotype showed larger
      tumors (proportion with size > 2 cm is 26 versus 55%, respectively; P = 0.07), a
      higher frequency of positive lymph nodes (28 versus 55%, respectively; P = 0.09),
      and a higher tumor-node-metastasis stage (proportion with stage III/IV: 6 versus
      25%, respectively; P = 0.04). The LL genotype is also associated with shorter
      survival than the VV and VL genotypes (P = 0.10). In conclusion, our findings do
      not provide evidence for an important role of the V89L polymorphism in the
      etiology of breast cancer. However, in breast cancer patients, the LL genotype
      may be associated with unfavorable prognosis.

PMID- 14652281
TI  - DNA-repair genetic polymorphisms and breast cancer risk.
AB  - Mammalian cells are constantly exposed to genotoxic agents from both endogenous
      and exogenous sources. Genetic variability in DNA repair contributes to deficient
      repair and breast cancer risk. Using samples collected in an ongoing, clinic
      based, case-control study (253 cases and 268 controls), we tested whether breast
      cancer risk is associated with four amino acid substitution variants in three DNA
      repair genes, including XRCC1 Arg194Trp and XRCC1 Arg399Gln in base excision
      repair, XRCC3 Thr241Met in homologous recombination repair, and ERCC4/XPF
      Arg415Gln in nucleotide excision repair. Carriers of at least one variant allele
      of XRCC1 Arg194Trp [Arg/Trp and Trp/Trp versus Arg/Arg, odds ratio (OR) = 1.60,
      95% confidence interval (CI) = 0.89-2.87] or two variant alleles of XRCC3
      241Met/Metmay have an increased risk of breast cancer (Met/Met versus Thr/Thr and
      Thr/Met, OR = 1.54, 95% CI = 0.94-2.52). No association between XRCC1 Arg399Gln
      Dgenotype and breast cancer risk was observed. The genotype distribution of
      ERCC4/XPF Arg415Gln differed significantly between cases and controls (P = 0.02),
      and the ERCC4/XPF 415Gln/Gln genotype was found in only seven cases (3%) but not
      in controls. In addition, breast cancer risk was significantly associated with an
      increasing number of combined variant alleles of XRCC1 Arg194Trp, XRCC3
      Thr241Met, and ERCC4/XPF Arg415Gln in a four-level model (P(trend) = 0.04): OR =
      1.0 for those without a variant allele (referent group); OR = 1.04 (95% CI = 0.67
      1.61) for those with one variant allele; OR = 1.38 (95% CI = 0.83-2.29) for those
      with two variant alleles; and age-adjusted OR = 2.60 (95% CI = 1.03-6.59) for
      those with three or more variant alleles after adjustment for age, family
      history, age at menarche, age at first live birth, and body mass index. We
      provide evidence that variants of XRCC1, XRCC3, and ERCC4/XPF genes, particularly
      in combination, contribute to breast cancer susceptibility.

PMID- 14652282
TI  - Interleukin-1 receptor antagonist gene polymorphism in epithelial ovarian cancer.
AB  - The development of malignant tumors is constituted by different immunological
      components. Interleukin (IL)-1 receptor antagonist (RA) is known to be critically
      involved in the carcinogenesis of different malignant solid tumors. Polymorphism
      of a specific gene can have an important effect on gene transcription, the
      stability of the mRNA, or the quantity and activity of the resulting protein. In
      a case-control study, we investigated the polymorphism of the IL-1RA gene in 162
      women with histologically proven ovarian cancer and 121 patients with benign
      gynecological diseases. Overall, 25.9% of the patients were diagnosed in
      International Federation of Gynecologists and Obstetricians (FIGO) stage I or II,
      and 74.1% of the patients were diagnosed in FIGO stage III or IV (study group).
      The distribution of genotype frequencies was significantly different between
      study and control group with respect to allele 1/2 heterozygotes (32.1% versus
      14.9%; P < 0.001). Furthermore, patients who were heterozygous at allele 2 for IL
      1 RA (IL-RA 1/2) had a significantly higher risk for ovarian cancer with an odds
      ratio of 2.7 (95% confidence interval, 1.5-4.9). There were no differences
      between IL-1 RA 1/2 polymorphism and other alleles in clinical parameters (e.g.,
      tumor stage, histological type, and recurrence status). Allele 2 polymorphism of
      the IL1-RA gene seems to be one of the critical points in the molecular pathway
      of different malignant diseases. This allele seems to play an additional role in
      the occurrence of ovarian cancer and should be further investigated for screening
      and risk evaluation.

PMID- 14652283
TI  - Serum enterolactone concentration is not associated with prostate cancer risk in
      a nested case-control study.
AB  - The lignan enterolactone, produced by the intestinal microflora from dietary
      precursors, has been hypothesized to protect against hormone-dependent cancers
      and cardiovascular diseases. We conducted a nested case-control study to examine
      the relationship between serum enterolactone concentration and prostate cancer.
      Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in
      serum collected at baseline in the alpha-Tocopherol, beta-Carotene Cancer
      Prevention Study from 214 men with prostate cancer diagnosed during a 6-year
      follow-up and from 214 controls matched by age, date of baseline blood
      collection, intervention group, and local study area. Mean serum enterolactone
      concentration (in nmol/liter) did not differ significantly between case and
      control subjects [15.9 (SD, 15.2) versus 16.9 (SD, 14.9), respectively (P =
      0.42)]. Odds ratios for prostate cancer risk estimated by conditional logistic
      regression for increasing quartiles of enterolactone concentration were 1.00
      (referent), 0.72 [95% confidence interval (CI), 0.43-1.23], 0.98 (95% CI, 0.58
      1.68), and 0.71 (95% CI, 0.42-1.21). Our findings do not support the hypothesis
      that enterolactone is involved in the development of prostate cancer.

PMID- 14652284
TI  - Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy
      isoflavones administered to individuals with cancer.
AB  - Preclinical studies suggest that the isoflavone genistein may have prostate
      cancer chemopreventive activity. Genistein has been shown to alter cellular
      levels of protein-tyrosine phosphorylation and is present at high levels in soy.
      This study was designed to measure the pharmacokinetic parameters of two
      different preparations of unconjugated soy isoflavones, PTI G-2535 and PTI G-4660
      (which contain 43% and 90% genistein, respectively), in human subjects with
      cancer, to evaluate toxicity and obtain pilot data on in vivo effects on protein
      tyrosine phosphorylation. Cohorts of four patients were given single doses of
      each preparation; each dose was separated by 1 week. Sequential cohorts received
      genistein at 2, 4, or 8 mg/kg orally. Pharmacokinetic sampling was performed
      after each dose, and tyrosine phosphorylation was measured in proteins extracted
      from peripheral blood mononuclear cells. One of 13 patients treated developed a
      treatment-related rash. No other toxicities were observed. Maximal plasma
      concentrations (C(max)) ranged between 4.3 and 16.3 micro M for total genistein
      and 0.066 and 0.17 micro M for free genistein. For PTI G-2535 and PTI G-4660,
      half-life was 15.03 and 22.41 h, respectively, and volume of distribution was
      189.9 and 653.8 liters, respectively, and there was a trend toward higher area
      under the concentration curve for PTI G-2535 (P = 0.07 at the 8 mg/kg dose).
      Treatment-related increases in tyrosine phosphorylation were observed in
      peripheral blood mononuclear cells. Oral administration of soy isoflavones gives
      plasma concentrations of genistein that have been associated with antimetastatic
      activity in vitro.

PMID- 14652285
TI  - Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related
      polymorphisms in Linxian, China.
AB  - Linxian, a rural county in North Central China, has among the highest rates of
      esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA)
      in the world. Its inhabitants have documented chronic nutritional inadequacies,
      including folate and vitamin B(12) deficiencies. Using a cohort we have been
      studying in Linxian since 1985, we examined the relationship between incident
      ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes
      that require folate and B(12) as cofactors: methionine synthase reductase (MTRR)
      A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We
      conducted a case-cohort study among 4005 individuals in our cohort who were alive
      and cancer free in 1991 and had blood samples adequate for DNA extraction.
      Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs)
      that developed through May 1996 and on 398 controls. Cox proportional hazard
      models were used to estimate relative risks (RRs) and 95% confidence intervals
      (CIs). Individuals with the MTHFR 677TT genotype had significantly higher
      combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02-2.05) than those with CC or CT
      genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P =
      0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG
      or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04
      2.42). No association was observed for GCA. Our results suggest that the MTHFR
      C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this
      population.

PMID- 14652286
TI  - Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes, and risk for
      esophageal squamous cell carcinoma in Japanese men.
AB  - Alcohol flushing after light drinking is triggered mainly by severe
      acetaldehydemia in individuals possessing inactive aldehyde dehydrogenase (ALDH)
      2. Inactive ALDH2 encoded by ALDH2*1/2*2 and the low-activity form of alcohol
      dehydrogenase (ADH)-2 encoded by ADH2*1/2*1 enhance the risk for esophageal
      cancer in Japanese light to heavy drinkers, a significant association that
      emphasizes the importance of screening tests for inactive ALDH2 based on alcohol
      flushing. The objectives of the present report were (a). to evaluate the
      reliability of a simple questionnaire that asks about both current and past
      flushing for detecting inactive ALDH2 and (b). to predict cancer risk based on
      flushing in a case-control manner. The study subjects consisted of 233 Japanese
      men with esophageal squamous cell carcinoma and 610 cancer-free Japanese men.
      When current or former flushing individuals were considered to have inactive
      ALDH2, the sensitivity and specificity of the test were 84.8% and 82.3%,
      respectively, for the cases and 90.1% and 88.0%, respectively, for the controls.
      To clarify the characteristics of men who had genetically inactive ALDH2 but did
      not report alcohol flushing, we analyzed individuals possessing the ALDH2*1/2*2
      genotype and found that those who also had ADH2*1/2*1 (both cases and controls)
      tended not to report current flushing, and those who did not report current
      flushing (controls only) tended to be heavier drinkers. As compared with overall
      never or rare drinking, the cancer risks for light (1-8.9 units/week; 1 unit = 22
      g of ethanol), moderate (9-17.9 units/week), and heavy (18+ units/week) drinkers
      with current or former flushing (odds ratio = 6.69, 42.66, and 72.86,
      respectively) significantly exceeded the risks for those who had never flushed
      (odds ratio = 1.27, 10.12, and 15.61, respectively), even after adjustment for
      age, smoking, and diet. The flushing questionnaire may be used in large-scale
      epidemiological studies as a surrogate marker of ALDH2 genotype to predict
      individual cancer risk.

PMID- 14652287
TI  - Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with
      environmental exposures, and bladder cancer risk in a case-control study in
      northern Italy.
AB  - Tobacco smoking and occupational exposures are the main known risk factors for
      bladder cancer, causing direct and indirect damage to DNA. Repair of DNA damage
      is under genetic control, and DNA repair genes may play a key role in maintaining
      genome integrity and preventing cancer development. Polymorphisms in DNA repair
      genes resulting in variation of DNA repair efficiency may therefore be associated
      with bladder cancer risk. A hospital-based case-control study was conducted in
      Brescia, Italy, to assess the relationship between polymorphisms in DNA repair
      genes XRCC1 (Arg(399)Gln), XRCC3 (Thr(241)Met), and XPD (Lys(751)Gln) and bladder
      cancer risk. A total of 201 male incident bladder cancer cases and 214 male
      controls with urological nonneoplastic diseases were recruited and frequency
      matched on age, period, and hospital of recruitment. Detailed information was
      collected using a semistructured questionnaire on demographic, dietary,
      environmental, and occupational factors. Genotypes were determined by PCR-RFLP
      analysis. The XRCC3 codon 241 variant genotype exhibited a protective effect
      against bladder cancer [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42
      0.93], which was prominent among heavy smokers (OR, 0.49; 95% CI, 0.28-0.88) but
      not among never and light smokers. No overall impact of the XRCC1 codon 399
      polymorphism was found (OR, 0.86; 95% CI, 0.59-1.28), but a protective influence
      of the homozygous variant was suggested among heavy smokers (OR, 0.38; 95% CI,
      0.14-1.02). XPD polymorphisms did not show an association with bladder cancer
      (OR, 0.92; 95% CI, 0.62-1.37). There was no statistical evidence of an
      interaction between these three genetic polymorphisms and either tobacco smoking
      or occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines.
      The XRCC3 codon 241 polymorphism had an overall protective effect against bladder
      cancer that was most apparent among heavy smokers. Similarly, the XRCC1 codon 399
      polymorphism also had a protective effect on bladder cancer among heavy smokers.
      The XPD polymorphism was not, however, associated with bladder cancer risk.

PMID- 14652288
TI  - Endogenous deoxyribonucleic Acid (DNA) damage in human tissues: a comparison of
      ethenobases with aldehydic DNA lesions.
AB  - Two types of endogenous DNA lesions, ethenobases [1,N(6)-ethenoadenine
      (epsilonA), 3,N(4)-ethenocytosine (epsilonC)] and aldehydic DNA lesions (ADLs),
      were measured in several tissues (liver, lung, kidney, colon, colon mucosa,
      cerebellum, and gray and white matter of the cerebrum) obtained postmortem during
      autopsy examinations of 12 individuals (6 males, 6 females; ages, 58-87 years).
      Issues relating to changes in levels of DNA damage with disease and after death
      were addressed. The extent of DNA damage in autopsy samples was not associated
      with the length of the postmortem interval and was similar to levels observed in
      surgery samples, suggesting that endogenous, steady-state levels of etheno
      adducts and of ADLs are relatively stable during the hours immediately after
      death. In this limited series of samples, and with a few possible exceptions, the
      disease status before death was not associated with increased endogenous DNA
      damage in the affected tissue. DNA ethenobases were lowest in the cerebellum
      (median molar ratios: epsilonA/A = 1.0 x 10(-8); epsilonC/C = 1.9 x 10(-8)) and
      highest in the gray matter (epsilonA/A = 2.9 x 10(-8); epsilonC/C = 4.8 x 10(-8))
      and white matter (epsilonA/A = 2.4 x 10(-8); epsilonC/C = 5.2 x 10(-8)) of the
      cerebrum. In other tissues, median values were 1.2-1.9 x 10(-8) for epsilonA/A
      and 2.0-3.3 x 10(-8) for epsilonC/C. There was a good correlation between the
      levels of epsilonA and epsilonC (r = 0.80, P < 0.0001). Levels of ADLs were
      similar in the liver, lung, kidney, and white matter of the cerebrum (median
      values: 5.7-7.9 ADLs/10(6) nucleotides), higher in the colon (11.3 x 10(-6)) and
      gray matter of the cerebrum (9.0 x 10(-6)) and lower in the cerebellum (3.7 x 10(
      6)). There was no correlation between levels of ethenobases and amounts of ADLs
      (epsilonA versus ADLs: r = 0.12, P = 0.33; epsilonC versus ADLs: r = 0.024, P =
      0.85). Although there was an interindividual variability in the extent of
      endogenous DNA damage (4-fold for epsilonA and epsilonC, 2-fold for ADLs), which
      may be determined, in part, by the capacity to repair DNA and may be related to
      the pathology or treatment of the patients, these results suggest that the
      cerebrum contains higher endogenous DNA damage than the other tissues. These data
      are in line with previous studies showing that brain tissues are more susceptible
      to oxidative stress and lipid peroxidation than other tissues.

PMID- 14652289
TI  - Cell cycle arrest biomarkers in human lung cancer cells after treatment with
      selenium in culture.
AB  - In the planning of future intervention trials using chemopreventive agents
      against lung cancer, it is critical to evaluate the effect on biomarkers
      implicated specifically in lung carcinogenesis. With the use of the H520 and H522
      human lung cancer cell lines, the present study showed that treatment with
      selenium (in the form of methylseleninic acid) inhibited cell growth, arrested
      cell cycle progression at G(1), and induced apoptosis as a late event. Because
      H520 cells were more sensitive to selenium than H522 cells (IC(50) of MSA was 2.5
      or 10 micro M for H520 or H522 cells, respectively, at 24 h), a panel of nine
      cell cycle regulatory proteins known to be involved in G(1)-->S transition was
      assessed by Western analysis using whole cell lysate from H520 cells. These nine
      proteins (DP1, cdc25A, cyclin A, cyclin B(1), cyclin D(1), cdk1, cdk5, p21(WAF1),
      and GADD153) have been reported previously by our laboratory to be modulated by
      MSA in human breast and prostate cancer cells. Our data showed that only four
      (DP1, cdc25A, p21(WAF1), and GADD153) of nine biomarkers produced the expected
      changes after treatment of lung cancer cells with MSA. This finding raises the
      possibility that the molecular targets sensitive to selenium modulation may be
      tissue specific. Thus, the selection of selenium biomarkers for evaluation in an
      intervention trial must be based on empirical data derived from the cancer cell
      type of interest.

PMID- 14652290
TI  - Urinary mutagenicity and colorectal adenoma risk.
AB  - We investigated urinary mutagenicity and colorectal adenoma risk in a clinic
      based, case-control study of currently nonsmoking cases (n = 143) and controls (n
      = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine
      samples, and mutagenicity was determined in Salmonella YG1024 +S9 (Ames test).
      Adenoma risk was 2.4-fold higher in subjects in the highest versus the lowest
      quintile of urinary mutagenicity (95% confidence interval = 1.1-5.1). Combining
      urinary mutagenicity with intake of meat-derived mutagenicity (from our earlier
      analysis) resulted in a 5.6-fold increase in adenoma risk (95% confidence
      interval = 2.2-13.9, comparing the highest with the lowest quintile). In our
      study population, diet may have contributed to mutagenic exposure, which was
      positively associated with colorectal adenoma risk.

PMID- 14652291
TI  - Analysis of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in human
      urine.
AB  - A new method was developed for the analysis of metabolites of the tobacco
      specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in
      human urine. The metabolites are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL) and its glucuronides (NNAL-O-Gluc and NNAL-N-Gluc). The sum of these
      metabolites, total NNAL, was measured with this method. Urine was treated with
      beta-glucuronidase, which converts NNAL-O-Gluc and NNAL-N-Gluc to NNAL. After
      solvent partitioning and further purification on a liquid-liquid extraction
      cartridge and by high-performance liquid chromatography, total NNAL was
      quantified by gas chromatography with nitrosamine selective detection. The new
      method is accurate and precise, and the results are in good agreement with those
      obtained using the traditional method, which quantifies NNAL and its glucuronides
      separately. Levels of total NNAL +/- SD (pmol/mg creatinine) were 2.60 +/- 1.30
      (n = 41) in smokers, 3.25 +/- 1.77 (n = 55) in snuff-dippers, and 0.042 +/- 0.020
      (n = 18) in nonsmokers exposed to environmental tobacco smoke. The new method is
      faster and more sensitive than the traditional method and should greatly
      facilitate studies on human uptake of NNK.

PMID- 14652292
TI  - Effects of dietary folate on ulcerative colitis-associated colorectal
      carcinogenesis in the interleukin 2- and beta(2)-microglobulin-deficient mice.
AB  - Folate supplementation may reduce the risk of colorectal dysplasia and cancer in
      subjects with chronic ulcerative colitis (UC). The interleukin (IL) 2- and
      beta(2)-microglobulin (beta(2)m)-deficient (IL-2(null) x beta(2)m(null)) mice
      spontaneously develop colon cancer in the setting of chronic UC. This study
      investigated the effects of dietary folate on the development of UC-associated
      colon cancer in the IL-2(null) x beta(2)m(null) mice. Weaning IL-2(null) x
      beta(2)m(null) mice were randomized to receive 0 (deficient; n = 40), 2 (basal
      requirement; control; n = 46), or 8 (supplemented; n = 36) mg folate/kg diet for
      32 weeks. At necropsy, all macroscopic colonic tumors were identified and
      histologically classified as dysplasia or adenocarcinoma. The incidence of high
      grade lesions (high-grade dysplasia/carcinoma in situ and invasive
      adenocarcinoma) in the folate-supplemented group was 46% lower than that in the
      control group (35.3% versus 65.1%, P = 0.009). The incidence of high-grade
      lesions in the folate-deficient group was also 49% lower than that in the control
      group (33.3% versus 65.1%, P = 0.007). The higher mortality rate in the folate
      deficient group compared with the other two groups (25% versus 6.5% and 5.6%, P <
      0.02) partially accounted for the low incidence of high-grade lesions in this
      group. These data indicate that dietary folate supplementation at 4x the basal
      dietary requirement significantly suppresses UC-associated colorectal
      carcinogenesis in the IL-2(null) x beta(2)m(null) mice. These data also suggest
      that folate deficiency may inhibit colorectal carcinogenesis in chronic UC.
      However, the high mortality observed in the folate-deficient group precludes a
      definitive conclusion concerning the effect of folate deficiency on UC-associated
      colorectal carcinogenesis in this model.

PMID- 14652293
TI  - Estrogen and androgen concentrations are not lower in the umbilical cord serum of
      pre-eclamptic pregnancies.
AB  - Reductions in breast cancer risk observed in daughters of pre-eclamptic
      pregnancies are hypothesized to be mediated by lower in utero estrogen
      concentrations. Whereas maternal urinary estriol excretion is generally lower in
      pre-eclamptic women, results for maternal blood concentrations are equivocal, and
      little is known about estrogen concentrations in the cord of pre-eclamptic
      pregnancies. Unconjugated estrogen and androgen concentrations were measured in
      mixed umbilical cord sera from 86 pre-eclamptic and 86 uncomplicated, singleton
      pregnancies, matched on length of gestation, maternal age, parity, and type of
      delivery. Pre-eclamptic and uncomplicated pregnancies were similar in maternal
      age, prepregnancy weight, maternal height, type of delivery, use and type of
      anesthesia, and sex of offspring. Estriol, estradiol, estrone,
      dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and
      testosterone concentrations measured in cord sera were not significantly
      different in pre-eclamptics compared with uncomplicated pregnancies. Estriol was
      9% lower (P = 0.43), and all of the other hormones were actually higher in pre
      eclamptics with testosterone and estradiol approaching statistical significance
      (P = 0.06 and P = 0.12, respectively). These data do not support the hypothesis
      that the lower breast cancer risk in daughters of pre-eclamptic pregnancies is
      explained by lower in utero estrogen exposure.

PMID- 14652295
TI  - Prohibitin 3' untranslated region polymorphism and breast cancer risk.

PMID- 14652294
TI  - Null association between prostate cancer and serum folate, vitamin B(6), vitamin
      B(12), and homocysteine.

PMID- 14652296
TI  - Dieting behaviors and risk of neural tube defects.
AB  - The authors examined whether maternal dieting behaviors were associated with
      increased neural tube defect (NTD) risk among offspring, using population-based,
      case-control data. The analysis included 538 cases and 539 nonmalformed controls
      delivered from 1989 to 1991 in selected California counties, and exposures were
      assessed by in-person maternal interview. Among four reported dieting behaviors
      involving restricted food intake, diets to lose weight (odds ratio=2.1, 95%
      confidence interval: 1.1, 4.1), fasting diets (odds ratio=5.8, 95% confidence
      interval: 1.7, 20.0), and eating disorders (odds ratio=1.7, 95% confidence
      interval: 0.8, 3.6) were associated with increased NTD risk during the first
      trimester of pregnancy. Risk estimates for these behaviors during the 3 months
      before conception tended to be closer to 1. The fourth behavior, "other special
      diets," was not associated with increased NTD risk during either period. Women
      also reported whether they took diet pills, laxatives, or diuretics, engaged in
      binge eating, induced vomiting, or exercised excessively from the first 3 months
      before conception through the end of pregnancy. Only the intake of diuretics was
      associated with substantially increased NTD risk (odds ratio=2.7, 95% confidence
      interval: 0.7, 10.2). This study suggests that maternal dieting behaviors
      involving restricted food intake during the first trimester may be associated
      with increased NTD risk.

PMID- 14652297
TI  - Weight loss: a determinant of hip bone loss in older men and women. The Rancho
      Bernardo Study.
AB  - The sex-specific effect of weight change on change in total hip bone mineral
      density was evaluated over 4 years (1992-1996) in 1,214 community-dwelling adults
      whose mean age at baseline was 71 years. Weight and bone mineral density (by dual
      energy x-ray absorptiometry) were assessed at two study visits. The average bone
      loss was 0.5% per year in both sexes; 29% of men and 28% of women lost at least
      1% of bone mineral density per year. More than one in five participants lost at
      least 1% of their body weight per year (21% of men and 23% of women). These
      weight losers were twice as likely as others to lose bone at the rate of at least
      1% per year. In analyses controlling for age, baseline weight, and lifestyle,
      weight loss was the strongest independent predictor of bone loss (odds ratios
      were 1.53 for men and 1.56 for women). Persons with weight loss of at least 1%
      per year were more likely to report fair or poor health and functional limitation
      at the second visit and to die within 2 years of the second visit; however, most
      did not report declining health, and most survived for at least 2 additional
      years.

PMID- 14652298
TI  - Is obesity associated with major depression? Results from the Third National
      Health and Nutrition Examination Survey.
AB  - Data from the Third National Health and Nutrition Examination Survey (1988-1994)
      were used to examine the relation between obesity and depression. Past-month
      depression was defined using criteria from the Diagnostic and Statistical Manual
      of Mental Disorders, Third Edition, and was measured with the Diagnostic
      Interview Schedule. Obesity was defined as a body mass index (weight (kg)/height
      (m)2) of 30 or higher. The authors compared risks of depression in obese and
      normal-weight (body mass index 18.5-24.9) persons. Obesity was associated with
      past-month depression in women (odds ratio (OR)=1.82, 95% confidence interval
      (CI): 1.01, 3.3) but was not significantly associated in men (OR=1.73, 95% CI:
      0.56, 5.37). When obesity was stratified by severity, heterogeneity in the
      association with depression was observed. Class 3 (severe) obesity (body mass
      index > or =40) was associated with past-month depression in unadjusted analyses
      (OR=4.98, 95% CI: 2.07, 11.99); the association remained strong after results
      were controlled for age, education, marital status, physician's health rating,
      dieting for medical reasons, use of psychiatric medicines, cigarette smoking, and
      use of alcohol, marijuana, and cocaine. These findings suggest that obesity is
      associated with depression mainly among persons with severe obesity. Prospective
      studies will be necessary to clarify the obesity-depression relation but await
      the identification of potential risk factors for depression in the obese.

PMID- 14652299
TI  - Association between gestational diabetes and pregnancy-induced hypertension.
AB  - Gestational diabetes and pregnancy-induced hypertension are common, and their
      relation is not well understood. The authors conducted a population-based case
      control study using 1992-1998 Washington State birth certificate and hospital
      discharge records to investigate this relation. Consecutive cases of pregnancy
      induced hypertension were divided into four groups based on International
      Classification of Diseases, Ninth Revision codes: eclampsia (n=154), severe
      preeclampsia (n=1,180), mild preeclampsia (n=5,468), and gestational hypertension
      (n=8,943). Cases were compared with controls who did not have pregnancy-induced
      hypertension (n=47,237). Gestational diabetes was more common in each case group
      (3.9% in eclamptics, 4.5% in severe preeclamptics, and 4.4% in both mild
      preeclamptics and those with gestational hypertension) than in controls (2.7%).
      After adjustment for body mass index, age, ethnicity, parity, and prenatal care,
      gestational diabetes was associated with increased risk of severe preeclampsia
      (odds ratio (OR)=1.5, 95% confidence interval (CI): 1.1, 2.1), mild preeclampsia
      (OR=1.5, 95% CI: 1.3, 1.8), and gestational hypertension (OR=1.4, 95% CI: 1.2,
      1.6). Gestational diabetes was more strongly associated with pregnancy-induced
      hypertension among women who received less prenatal care (OR=4.2 for eclampsia
      and OR=3.1 for severe preeclampsia, p<0.05 for both) and among Black women (OR
      for eclampsia and preeclampsia together=3.9, p<0.05).

PMID- 14652300
TI  - Community-based study of hepatitis C virus infection and type 2 diabetes: an
      association affected by age and hepatitis severity status.
AB  - Past studies of the relation between hepatitis C virus (HCV) infection and type 2
      diabetes conflict. The authors aimed to elucidate the relation by using a large
      community-based sample with a wide range of liver conditions. Between October
      1997 and February 1998, 2,327 consecutive subjects (aged > or =35 years) were
      enrolled at the public health facility in Taiwan. Blood sugar, hepatitis B
      surface antigen, and antibody for HCV (anti-HCV) were tested. Abdominal
      sonography was performed on viral-hepatitis-positive subjects. In univariate
      analysis, older age, lower educational levels, sedentary work, body mass index of
      > or 25 kg/m2, and anti-HCV positivity were significantly associated with type 2
      diabetes (p<0.05), but smoking, alcohol consumption, gender, and hepatitis B
      surface antigen status were not. In multivariate logistic regression, anti-HCV
      positivity was strongly associated with type 2 diabetes in subjects aged 35-49
      years (odds ratio (OR)=3.3, 95% confidence interval (CI): 1.4, 8.0) and 50-64
      years (OR=1.6, 95% CI: 1.1, 2.5). Sonographic evidence of fatty liver (OR=2.4,
      95% CI: 1.2, 4.8) and chronic liver disease (OR=2.0, 95% CI: 1.0, 4.2) in anti
      HCV-positive subjects was moderately associated with type 2 diabetes after age
      and gender adjustment. Data suggest that HCV infection is moderately associated
      with type 2 diabetes; the association was strongest for subjects aged 35-49 years
      and increased with severity of the liver condition.

PMID- 14652301
TI  - Association of total and central obesity with mortality in postmenopausal women
      with coronary heart disease.
AB  - Overweight and abdominal obesity increase mortality risk, although the risk may
      be mediated by traditional cardiac risk factors. The authors assessed the
      association of baseline measures, change in overall body weight and abdominal
      obesity (waist circumference), and weight and waist circumference cycling with
      total mortality among postmenopausal women with known heart disease. They used
      data from 2,739 US women who participated in the Heart and Estrogen/progestin
      Replacement Study between 1993 and 2001. Over 6.8 years of follow-up, 498 women
      died. In adjusted Cox models that included either baseline waist circumference or
      body mass index (BMI), each was associated with mortality. However, after further
      adjustment for diabetes, hypertension, and lipoproteins, these associations
      disappeared. In models including both waist circumference and BMI, larger waist
      circumference (hazard ratio=1.40 per standard deviation, 95% confidence interval:
      1.16, 1.68) was associated with increased risk and higher BMI (hazard ratio=0.81
      per standard deviation, 95% confidence interval: 0.67, 0.97) was associated with
      decreased risk of total mortality, independent of cardiac risk factors. Weight
      and waist circumference cycling were not associated with mortality. Results show
      that both BMI and waist circumference are associated with mortality among
      postmenopausal women with established heart disease, but waist circumference may
      be more important than BMI, and their effects may be largely mediated by other
      cardiac risk factors.

PMID- 14652302
TI  - Lung function and incident coronary heart disease: the Atherosclerosis Risk in
      Communities Study.
AB  - The authors examined the association between lung function, as measured by forced
      expiratory volume in 1 second (FEV1) and forced vital capacity, and the 10-year
      incidence of coronary heart disease among 14,480 participants in the
      Atherosclerosis Risk in Communities Study (1987-1998). Separate proportional
      hazards models were used for FEV1 and forced vital capacity, with gender-specific
      lung function quartiles and lung function x gender interaction terms. An
      association between lung function and coronary heart disease was observed in both
      genders and was stronger among women. After adjustment for age, race, study
      center, height, height squared, smoking, and cardiovascular disease risk factors,
      the hazard ratios for the first (lowest), second, and third quartiles of FEV1
      were 3.70 (95% confidence interval (CI): 2.19, 6.24), 2.54 (95% CI: 1.49, 4.32),
      and 2.25 (95% CI: 1.31, 3.87) for women and 1.51 (95% CI: 1.07, 2.13), 1.59 (95%
      CI: 1.15, 2.20), and 1.52 (95% CI: 1.10, 2.09) for men. After stratification by
      smoking status, associations were observed in each smoking group for women, while
      those in men were weaker and less consistent. Similar results were obtained for
      forced vital capacity. This analysis indicates an association between lung
      function and incident coronary heart disease that may be stronger in women than
      in men.

PMID- 14652303
TI  - Cancer risk among workers at Danish companies using trichloroethylene: a cohort
      study.
AB  - Trichloroethylene is an animal carcinogen with limited evidence of
      carcinogenicity in humans. Cancer incidence between 1968 and 1997 was evaluated
      in a cohort of 40,049 blue-collar workers in 347 Danish companies with documented
      trichloroethylene use. Standardized incidence ratios for total cancer were 1.1
      (95% confidence interval (CI): 1.04, 1.12) in men and 1.2 (95% CI: 1.14, 1.33) in
      women. For non-Hodgkin's lymphoma and renal cell carcinoma, the overall
      standardized incidence ratios were 1.2 (95% CI: 1.0, 1.5) and 1.2 (95% CI: 0.9,
      1.5), respectively; standardized incidence ratios increased with duration of
      employment, and elevated standardized incidence ratios were limited to workers
      first employed before 1980 for non-Hodgkin's lymphoma and before 1970 for renal
      cell carcinoma. The standardized incidence ratio for esophageal adenocarcinoma
      was 1.8 (95% CI: 1.2, 2.7); the standardized incidence ratio was higher in
      companies with the highest probability of trichloroethylene exposure. In a
      subcohort of 14,360 presumably highly exposed workers, the standardized incidence
      ratios for non-Hodgkin's lymphoma, renal cell carcinoma, and esophageal
      adenocarcinoma were 1.5 (95% CI: 1.2, 2.0), 1.4 (95% CI: 1.0, 1.8), and 1.7 (95%
      CI: 0.9, 2.9), respectively. The present results and those of previous studies
      suggest that occupational exposure to trichloroethylene at past higher levels may
      be associated with elevated risk for non-Hodgkin's lymphoma. Associations between
      trichloroethylene exposure and other cancers are less consistent.

PMID- 14652304
TI  - Case-control study of bladder cancer and drinking water arsenic in the western
      United States.
AB  - Numerous epidemiologic investigations have identified links between high
      concentrations of arsenic in drinking water and cancer, although the risks at
      lower exposures are largely unknown. This paper presents the results of a case
      control study of arsenic ingestion and bladder cancer in seven counties in the
      western United States. These counties contain the largest populations
      historically exposed to drinking water arsenic at concentrations near 100
      microg/liter. All incident cases diagnosed from 1994 to 2000 were recruited.
      Individual data on water sources, water consumption patterns, smoking, and other
      factors were collected for 181 cases and 328 controls. Overall, no increased
      risks were identified for arsenic intakes greater than 80 microg/day (odds
      ratio=0.94, 95% confidence interval: 0.56, 1.57; linear trend, p=0.48). These
      risks are below predictions based on high dose studies from Taiwan. When the
      analysis was focused on exposures 40 or more years ago, an odds ratio of 3.67
      (95% confidence interval: 1.43, 9.42; linear trend, p<0.01) was identified for
      intakes greater than 80 microg/day (median intake, 177 microg/day) in smokers.
      These data provide some evidence that smokers who ingest arsenic at
      concentrations near 200 microg/day may be at increased risk of bladder cancer.

PMID- 14652305
TI  - Sense of coherence and mortality in men and women in the EPIC-Norfolk United
      Kingdom prospective cohort study.
AB  - This study tested the hypothesis that a personality disposition defined by a
      strong sense of coherence is associated with a reduced risk of mortality. The
      authors prospectively examined, for < or =6 years, the relation between a strong
      sense of coherence and mortality due to all causes, cardiovascular disease, and
      cancer among 20,579 participants aged 41-80 years from the European Prospective
      Investigation into Cancer (EPIC)-Norfolk Study in the United Kingdom. Data were
      collected in 1996-2002. Participants were recruited by post from general practice
      age-sex registers and subsequently completed a postal assessment of their sense
      of coherence. During follow-up, 1,024 deaths were recorded. A strong sense of
      coherence was associated with a 30% reduction in mortality from all causes (rate
      ratio=0.69, p<0.0001), cardiovascular disease (rate ratio=0.70, p=0.001), and
      cancer (rate ratio=0.74, p=0.003), independent of age, sex, and prevalent chronic
      disease. These associations were consistent by sex, except that no association
      was observed for cancer mortality in women. The association for all-cause
      mortality remained after adjustment for cigarette smoking history, social class,
      body mass index, systolic blood pressure, cholesterol, hostility, and neuroticism
      (rate ratio=0.76, p=0.002). Results suggest that a strong sense of coherence may
      confer some resilience to the risk of chronic disease.

PMID- 14652306
TI  - Snippets from the past: 70 years ago in the Journal.

PMID- 14652307
TI  - Validity and reproducibility of a food frequency questionnaire by cognition in an
      older biracial sample.
AB  - It is not currently known how dietary assessment in older persons is affected by
      cognition. In a 1997-2000 study, the authors assessed the validity and
      reproducibility of a modified Harvard self-administered food frequency
      questionnaire (SFFQ) among 118 Black and 114 White randomly selected
      participants, aged 68-99 years, of the Chicago Health and Aging Project.
      Participants completed multiple 24-hour dietary recall interviews (mean=3.6) over
      12 months and two SFFQs in the first and 12th months. The average energy-adjusted
      intraclass correlation coefficient for 15 nutrients was 0.59 for 1-year
      reproducibility in nutrient intake levels assessed by the SFFQ. The average
      energy-adjusted Pearson correlation coefficient was 0.46 for comparative validity
      between nutrient intake levels on the SFFQ and the dietary recalls. SFFQ
      reproducibility was higher among men, and comparative validity with the dietary
      recalls was higher among women. There were no remarkable differences in the
      correlations by age, race, educational level, presence of chronic conditions, or
      cognitive ability. The modified Harvard SFFQ is a reasonable method of dietary
      assessment even in a population of older persons, some of whom are at advanced
      age, have chronic health conditions, and have cognitive impairment.

PMID- 14652308
TI  - Sources of variability in blood pressure measurement using the Dinamap PRO 100
      automated oscillometric device.
AB  - The Dinamap automated oscillometric device (GE Medical Systems Information
      Technologies, Inc., Milwaukee, Wisconsin) for blood pressure measurement is
      widely employed in epidemiologic studies because it is easy to use and because it
      eliminates observer variability. In this study, the authors assessed the
      variability in observed blood pressures associated with use of the Dinamap
      monitor and estimated the contributions of various factors to that variability.
      In 60 volunteers (30 aged 23-35 years and 30 aged 54-82 years) from New York, New
      York, the authors obtained 30 simultaneous paired blood pressure measurements in
      both arms at 1-minute intervals, using three separate Dinamap PRO 100 devices
      allocated to arm and subject according to a balanced incomplete block design.
      Variability, defined as the between-arm difference in blood pressure
      measurements, was analyzed using a mixed-effects linear regression model. A total
      of 1,800 paired blood pressure measurements were obtained between September 2001
      and June 2002. The mean ages of the two groups were 28.3 years (standard
      deviation, 4.0) and 71.7 years (standard deviation, 8.0). A diagnosis of
      hypertension was present in 53% of the older subjects and none of the younger
      subjects. Fifty percent of paired simultaneous blood pressure measurements
      obtained were in agreement within 4 mmHg for systolic blood pressure or within 3
      mmHg for diastolic blood pressure. Residual variability, attributable to the
      intrinsic inaccuracy of the device, accounted for 64-82% of the total systolic
      and diastolic blood pressure variability. The majority of variability in blood
      pressure measurement was due to the device as used under the study conditions.

PMID- 14652310
TI  - Re: Influence of maternal glucose level on ethnic differences in birth weight and
      pregnancy outcome.

PMID- 14652312
TI  - Making the grade in public health advocacy.

PMID- 14652313
TI  - The reality of racial/ethnic bias in health care.

PMID- 14652315
TI  - Pitfalls in using internet references.

PMID- 14652317
TI  - Latin American social medicine: the quest for social justice and public health.

PMID- 14652318
TI  - Public health in China: the Shanghai CDC perspective.

PMID- 14652319
TI  - Latin American social medicine and global social medicine.
AB  - A fundamental change in the theory underlying public health and medicine is
      needed. Latin American social medicine (LASM), originating in a region of the
      world that has been subjected to colonial and postcolonial influence, will be
      part of this change. To the extent that the social production of disease among
      people in other regions is a consequence of various large-scale forms of
      domination, LASM offers a relevant analysis, models of resistance, and exemplars
      of social medicine in practice. I draw upon LASM to examine the social production
      of disease in the Marshall Islands and Iraq. I suggest a basis for a global
      social medicine in the shared experience of suffering and describe implications
      for public health theory and practice.

PMID- 14652320
TI  - Protecting the public from mercury exposure: success through microexchange
      events.
AB  - Mercury is a growing environmental threat that can cause serious health problems
      and birth defects. Household thermometers are high-risk sources of mercury
      because most people lack the knowledge to properly dispose of one when it is
      broken. The Boston Public Health Commission's Environmental Health Office, with
      local and national partners, created the Boston Mercury Thermometer Exchange
      Program to address this hazard. Large central exchanges are successful, but
      multiple smaller targeted "microexchanges" can be another effective way to reach
      the general public and specific vulnerable subpopulations such as the elderly,
      the homebound disabled, or recent immigrants. By conducting exchanges in
      community health centers and public housing developments for the elderly and
      disabled, and by working through home health care providers, the program
      collected 4477 thermometers.

PMID- 14652321
TI  - Low breastfeeding rates and public health in the United States.
AB  - The medical community has orchestrated breastfeeding campaigns in response to low
      breastfeeding rates twice in US history. The first campaigns occurred in the
      early 20th century after reformers linked diarrhea, which caused the majority of
      infant deaths, to the use of cows' milk as an infant food. Today, given studies
      showing that numerous diseases and conditions can be prevented or limited in
      severity by prolonged breastfeeding, a practice shunned by most American mothers,
      the medical community is again inaugurating efforts to endorse breastfeeding as a
      preventive health measure. This article describes infant feeding practices and
      resulting public health campaigns in the early 20th and 21st centuries and finds
      lessons in the original campaigns for the promoters of breastfeeding today.

PMID- 14652322
TI  - Public health in Central America.

PMID- 14652323
TI  - Considerations on human capital. 1939.

PMID- 14652324
TI  - Salvador Allende: physician, socialist, populist, and president.

PMID- 14652325
TI  - Globalization and health at the United States-Mexico border.
AB  - OBJECTIVES: We studied the impact of globalization on the making of health
      policy. Globalization is understood as economic interdependence among nations.
      The North American Free Trade Agreement is used as a marker to assess the effects
      of economic interdependence on binational health cooperation along the United
      States-Mexico border. METHODS: We observed participants and conducted in-depth
      interviews with policymakers, public health specialists, representatives of
      professional organizations, and unions. RESULTS: Globalization has not promoted
      binational health policy cooperation. Barriers that keep US and Mexican
      policymakers apart prevail while health problems that do not recognize
      international borders go unresolved. CONCLUSIONS: If international health
      problems are to be solved, political, cultural, and social interdependence need
      to be built with the same impetus by which policymakers promote international
      trade.

PMID- 14652326
TI  - Latin American social medicine: roots, development during the 1990s, and current
      challenges.
AB  - Latin American social medicine arose during the 1950s and 1960s, drawing its
      inspiration from the social movements that emerged in France, Germany, and
      England in the mid-19th century. The Latin American movement of social medicine
      has clear ideological goals. It is organized around the Latin American
      Association of Social Medicine, which was founded in 1984 and is regarded as a
      social, political, and academic movement. This article takes a historical
      perspective and presents the reasons for the emergence and identity of the
      association, focusing on the main developments and contributions of this movement
      from the 1990s until the present time.

PMID- 14652327
TI  - What does Latin Aamerican social medicine do when it governs? The case of the
      Mexico City government.
AB  - Latin American social medicine (LASM) emerged as a movement in the 1970s and
      played an important role in the Brazilian health care reform of the 1980s, both
      of which focused on decentralization and on health care as a social right. The
      dominant health care reform model in Latin America has included a market-driven,
      private subsystem for the insured and a public subsystem for the uninsured and
      the poor. In contrast, the Mexico City government has launched a comprehensive
      policy based on social rights and redistribution of resources. A universal
      pension for senior citizens and free medical services are financed by grants,
      eliminating routine government corruption and waste. The Mexico City policy
      reflects the influence of Latin American social medicine. In this article, I
      outline the basic traits of LASM and those of the prevailing health care reform
      model in Latin America and describe the Mexico City social and health policy,
      emphasizing the influence of LASM in values, principles, and concrete programs.

PMID- 14652328
TI  - A social-medical approach to violence in Colombia.
AB  - Violence is the main public health problem in Colombia. Many theoretical and
      methodological approaches to solving this problem have been attempted from
      different disciplines. My past work has focused on homicide violence from the
      perspective of social medicine. In this article I present the main conceptual and
      methodological aspects and the chief findings of my research over the past 15
      years. Findings include a quantitative description of the current situation and
      the introduction of the category of explanatory contexts as a contribution to the
      study of Colombian violence. The complexity and severity of this problem demand
      greater theoretical discussion, more plans for action and a faster transition
      between the two. Social medicine may make a growing contribution to this field.

PMID- 14652329
TI  - Research on health inequalities in Latin America and the Caribbean: bibliometric
      analysis (1971-2000) and descriptive content analysis (1971-1995).
AB  - We conducted a bibliometric and content analysis of research on health
      inequalities produced in Latin American and Caribbean countries. In our
      bibliometric analysis (n = 576), we used indexed material published between 1971
      and 2000. The content analysis (n = 269) covered the period 1971 to 1995 and
      included unpublished material. We found recent rapid growth in overall output.
      Brazil, Chile, and Mexico contributed mostly empirical research, while Ecuador
      and Argentina produced more conceptual studies. We found, in the literature
      reviewed, a relative neglect of gender, race, and ethnicity issues. We also found
      remarkable diversity in research designs, however, along with strong
      consideration of ecological and ethnographic methods absent in other research
      traditions.

PMID- 14652330
TI  - Childhood adversity and later mortality in an urban African American cohort.

PMID- 14652331
TI  - Vaccination coverage of American Indian/Alaska native children aged 19 to 35
      months: findings from the National Immunization Survey, 1998-2000.

PMID- 14652332
TI  - Relation of occupational change to cardiovascular risk factor levels in rural
      Chinese men: the People's Republic of China-United States Collaborative Study on
      Cardiovascular and Cardiopulmonary Epidemiology.

PMID- 14652333
TI  - Undiagnosed hypertension and hypercholesterolemia among uninsured and insured
      adults in the Third National Health and Nutrition Examination Survey.

PMID- 14652334
TI  - Environmental tobacco smoke and adult-onset asthma: a population-based incident
      case-control study.
AB  - OBJECTIVES: The authors assessed the effects of environmental tobacco smoke (ETS)
      on the development of asthma in adults. METHODS: In the Pirkanmaa district of
      South Finland, all 21- to 63-year-old adults with new cases of asthma diagnosed
      during a 2.5-year period (n = 521 case patients, out of 441 000 inhabitants) and
      a random sample of control subjects from the source population (932 control
      subjects) participated in a population-based incident case-control study.
      RESULTS: Risk of asthma was related to workplace ETS exposure (adjusted odds
      ratio [OR] = 2.16; 95% confidence interval [CI] = 1.26, 3.72) and home exposure
      (OR = 4.77; 95% CI = 1.29, 17.7) in the past year. Cumulative ETS exposure over a
      lifetime at work and at home increased the risk. CONCLUSIONS: This study
      indicates for the first time that both cumulative lifetime and recent ETS
      exposures increase the risk of adult-onset asthma.

PMID- 14652335
TI  - Depression in adult women: age changes and cohort effects.
AB  - OBJECTIVES: We sought to separate age and cohort associations with depression,
      assessed 3 times within a 10-year period in 701 women born between 1928 and 1958.
      METHODS: We used regression analysis to examine age differences in women with
      depression in 2 birth cohorts, pre-1945 and post-1944, who were assessed at
      comparable ages. Multilevel modeling was used to estimate changes with age in
      successive birth year cohorts. RESULTS: An age by cohort interaction indicated
      more depression among younger than older women in the post-1944 cohort but a flat
      age profile in the pre-1945 cohort. Longitudinal analyses indicated declines in
      depression with age in more recent cohorts but increases in earlier ones.
      CONCLUSIONS: Increases in depression in younger women in successive cohorts may
      be offset by decreases in middle age.

PMID- 14652336
TI  - Racial and ethnic disparities in emergency department analgesic prescription.
AB  - OBJECTIVES: We examined racial and ethnic disparities in analgesic prescription
      among a national sample of emergency department patients. METHODS: We analyzed
      Black, Latino, and White patients in the 1997-1999 National Hospital Ambulatory
      Medical Care Surveys to compare prescription of any analgesics and opioid
      analgesics by race/ethnicity. RESULTS: For any analgesic, no association was
      found between race and prescription; opioids, however, were less likely to be
      prescribed to Blacks than to Whites with migraines and back pain, though race was
      not significant for patients with long bone fracture. Differences in opioid use
      between Latinos and Whites with the same conditions were less and nonsignificant.
      CONCLUSIONS: Physicians were less likely to prescribe opioids to Blacks; this
      disparity appears greatest for conditions with fewer objective findings (e.g.,
      migraine).

PMID- 14652337
TI  - Racial/ethnic differences in influenza vaccination coverage in high-risk adults.
AB  - OBJECTIVES: This study identified racial/ethnic disparities in influenza
      vaccination in high-risk adults. METHODS: We analyzed data on influenza
      vaccination in 7655 adults with high-risk conditions, using data from the 1999
      National Health Interview Survey (NHIS). We stratified data by age and used
      multiple logistic regression to adjust for gender, education, income, employment,
      and health care access. RESULTS: After control for covariates, White patients
      with diabetes, chronic heart conditions, and cancer had a higher prevalence of
      influenza vaccination than did Black patients with the same conditions.
      Similarly, White patients with 2 or more high-risk conditions were more likely to
      receive the influenza vaccine than Black patients with the same conditions.
      CONCLUSIONS: Significant racial/ethnic differences exist in influenza vaccination
      of high-risk individuals, and missed vaccination opportunities seem to contribute
      to the less-than-optimal influenza vaccination coverage in the United States.

PMID- 14652338
TI  - Substance use, dependence, and service utilization among the US uninsured
      nonelderly population.
AB  - OBJECTIVES: We examined the prevalence and correlates of substance use,
      dependence, and service utilization among uninsured persons aged 12 to 64 years.
      METHODS: We drew study data from the 1998 National Household Survey on Drug
      Abuse. RESULTS: An estimated 80% of uninsured nonelderly persons reported being
      uninsured for more than 6 months in the prior year. Only 9% of these uninsured
      persons who were dependent on alcohol or drugs had received any substance abuse
      service in the past year. Non-Hispanic Whites were an estimated 3 times more
      likely than Blacks to receive substance abuse services. CONCLUSIONS: Compared
      with the privately insured, uninsured persons had increased odds of having
      alcohol/drug dependence and appeared to face substantial barriers to health
      services for substance use problems.

PMID- 14652339
TI  - Delivering equitable care: comparing preventive services in Manitoba.
AB  - OBJECTIVES: This study examined preventive care delivered in Manitoba during the
      1990s by 3 different methods -childhood immunizations (by physicians and public
      health nurses under a government program), screening mammography (through a
      government program introduced in 1995), and cervical cancer screening (no
      program). METHODS: Longitudinal administrative data, an immunization monitoring
      system, and Canadian census databases were used. RESULTS: Cervical cancer
      screening rates remained static and showed strong socioeconomic differences;
      childhood immunization rates remained high with small socioeconomic gradients.
      The introduction of the Manitoba Breast Screening Program resulted in rising
      rates of screening and vanishing socioeconomic gradients. CONCLUSIONS: Manitoba
      government programs in childhood immunization and screening mammography actively
      helped the provision of preventive care. Organized programs that target
      population groups, recognize barriers to access, and facilitate self-evaluation
      are critical for equitable delivery.

PMID- 14652340
TI  - Healthy People 2010 and Asian Americans/Pacific Islanders: defining a baseline of
      information.
AB  - OBJECTIVES: Healthy People 2010: Understanding and Improving Health lists 6 areas
      of disparity in minority health services: infant mortality, cancer,
      cardiovascular disease, HIV/AIDS, diabetes, and immunizations. This study
      compiles existing Asian American and Pacific Islander (AAPI) health data to
      establish a baseline. METHODS: For federally-sponsored research (1986-2000), the
      Computer Retrieval of Information on Specific Projects (CRISP) database was
      analyzed. AAPI initiatives were divided by subpopulation and disparity area.
      MEDLINE articles (1966-2000) were similarly scrutinized. RESULTS: Few federal
      health-related grants (0.2%) and MEDLINE articles (0.01%) mention AAPIs. For the
      6 disparity areas, significant AAPI data gaps remain. CONCLUSIONS: To reach the
      Healthy People 2010 goals and have useful data, researchers and grant makers must
      focus on obtaining baseline data for disaggregated AAPI subgroups.

PMID- 14652341
TI  - Secular trends in adolescent never smoking from 1990 to 1999 in California: an
      age-period-cohort analysis.
AB  - OBJECTIVES: We analyzed age, time period, and cohort effects on trends in
      adolescent cigarette smoking in California from 1990 to 1999. METHODS: Data from
      subjects aged 12 to 17 years (n = 26 536; 50.4% male) from the California Tobacco
      Survey and the California Youth Tobacco Survey were analyzed, and never smokers
      were used as the outcome measure. RESULTS: The proportion of never smokers
      increased from 60% for males and 66% for females in 1990 to around 70% for both
      sexes in 1999. Respondents were more likely to be never smokers if born in 1978
      or later (i.e., aged 12 years or younger in 1990, when most tobacco control
      programs started in California). CONCLUSIONS: The statewide antitobacco programs
      prevented adolescents from starting to smoke, primarily through a cohort effect.

PMID- 14652342
TI  - The association of race, socioeconomic status, and health insurance status with
      the prevalence of overweight among children and adolescents.
AB  - OBJECTIVES: We examined the effect of race, socioeconomic status, and health
      insurance status on the prevalence of overweight among children and adolescents.
      METHODS: We studied an observational cohort from the 1996 Medical Expenditure
      Panel Survey Household Component. RESULTS: In the younger group, both Black and
      Latino children had a greater likelihood of being overweight compared with White
      children. Among the adolescent group, Latinos and Asian/Pacific Islanders were
      more likely to be overweight. Among adolescents, lacking health insurance and
      having public insurance were both positively associated with the prevalence of
      overweight. A relationship between insurance status and overweight was not
      observed for younger children. CONCLUSIONS: There are substantial racial
      differences in the prevalence of overweight for children and adolescents. Health
      insurance status is associated with the prevalence of overweight among
      adolescents.

PMID- 14652343
TI  - Patient attitudes, insurance, and other determinants of self-referral to medical
      and chiropractic physicians.
AB  - OBJECTIVES: This study identified predictors of patient choice of a primary care
      medical doctor or chiropractor for treatment of low back pain. METHODS: Data from
      initial visits were derived from a prospective, longitudinal, nonrandomized,
      practice-based observational study of patients who self-referred to medical and
      chiropractic physicians (n = 1414). RESULTS: Logistic regression showed
      differences between patients who sought care from medical doctors vs
      chiropractors in terms of patient health status, sociodemographic
      characteristics, insurance, and attitudes. Disability, insurance, and trust in
      provider types were particularly important predictors. CONCLUSIONS: The study
      highlights the importance of patient attitudes, health status, and insurance in
      self-referral decisions. The significance of patient attitudes suggests that
      education might be used to shape attitudes and encourage cost-effective care
      choices.

PMID- 14652344
TI  - Risk factors for sporadic Campylobacter jejuni infections in rural michigan: a
      prospective case-control study.
AB  - OBJECTIVES: This case-control study investigated risk factors for
      campylobacteriosis in a rural population. Exposure to live farm animals was
      hypothesized to increase the risk for Campylobacter jejuni enteritis. METHODS:
      Incident cases from rural counties reported to the Michigan Department of
      Community Health and matched controls completed a self-administered postal
      questionnaire. RESULTS: Persons engaged in poultry husbandry had increased odds
      of campylobacteriosis (odds ratio = 6.884; 95% confidence interval (CI) = 1.438,
      32.954). There was evidence for a dose-response relationship between the number
      of types of poultry contact and campylobacteriosis. CONCLUSIONS: We estimate that
      18% (95% CI = 6%, 30%) of Campylobacter cases occurring in rural populations are
      attributable to poultry husbandry. Cases occurred in individuals who were not
      poultry farmers by occupation.

PMID- 14652345
TI  - Winners and losers: expansion of insurance coverage in Russia in the 1990s.
AB  - OBJECTIVES: This study sought to describe the evolution of the Russian compulsory
      health insurance system and to identify factors associated with noncoverage.
      METHODS: Data from successive waves of the Russian Longitudinal Monitoring Survey
      (1992-2000) were analyzed. RESULTS: Insurance coverage grew rapidly throughout
      the 1990s, although 11.8% of the country's citizens were still uninsured by 2000.
      Coverage initiation rates were greater at first among citizens who were better
      off, but this gap closed over the study period. Among individuals of working age,
      coverage rates diminished with age and were lower for the unemployed, for the
      self-employed, and for those residing outside Moscow or St. Petersburg.
      CONCLUSIONS: The growth of insurance coverage in Russia slowed toward the end of
      the 1990s, and gaps remain. Achievement of universal coverage will require new,
      targeted policies.

PMID- 14652346
TI  - Domestic elder abuse and the law.
AB  - OBJECTIVES: The authors evaluated the impact of state adult protective service
      legislation on rates of investigated and substantiated domestic elder abuse.
      METHODS: Data were collected on all domestic elder abuse reports, investigations,
      and substantiations for each US state and the District of Columbia for 1999.
      State statutes and regulations pertaining to adult protective services were
      reviewed. RESULTS: There were 190 005 domestic elder abuse reports from 17
      states, a rate of 8.6 per 1000 elders; 242 430 domestic elder abuse
      investigations from 47 states, a rate of 5.9; and 102 879 substantiations from 35
      states, a rate of 2.7. Significantly higher investigation rates were found for
      states requiring mandatory reporting and tracking of numbers of reports.
      CONCLUSIONS: Domestic elder abuse documentation among states shows substantial
      differences related to specific aspects of state laws.

PMID- 14652347
TI  - 2003 W.O. Atwater Memorial Lecture: Defining nutrient requirements from a
      perspective of bone-related nutrients.

PMID- 14652348
TI  - LaVell Merl Henderson (1917-1999).

PMID- 14652349
TI  - Brittmarie Sandstrom (1945-2002).

PMID- 14652350
TI  - Milton Leonard Scott (1915-2001).

PMID- 14652351
TI  - Zinc oxide protects cultured enterocytes from the damage induced by Escherichia
      coli.
AB  - There is some evidence that zinc oxide (ZnO) protects against intestinal
      diseases. However, despite the suggestions that ZnO may have an antibacterial
      effect, the mechanisms of this protective effect have not yet been elucidated. We
      investigated the potential benefits of ZnO in protecting intestinal cells from
      damage induced by enterotoxigenic Escherichia coli (ETEC, strain K88) and the
      related mechanisms, using human Caco-2 enterocytes. Cell permeability, measured
      as transepithelial electrical resistance (TEER), was unaffected by 0.01 and 1
      mmol/L ZnO treatments and moderately increased by 5 mmol/L ZnO, compared with
      untreated cells. Transfer of (14)C-inulin was slightly increased by 5 mmol/L ZnO
      compared with untreated cells; transfer was unaffected by lower concentrations.
      The TEER and (14)C-inulin transfer were lower in ETEC-infected cells than in
      uninfected cells. Treatment of ETEC exposure with 0.2 mmol/L ZnO prevented
      disruption of membrane integrity. The ETEC was able to adhere to enterocytes and,
      to some extent, invade the cells. The ZnO treatment reduced bacterial adhesion
      and blocked bacterial invasion. The ETEC infection upregulated the expression of
      the inflammatory cytokines interleukin-8, growth-related oncogene-alpha and tumor
      necrosis factor-alpha, and reduced that of the anti-inflammatory cytokine
      transforming growth factor-beta, compared with uninfected cells. The addition of
      0.2 or 1 mmol/L ZnO counteracted the alteration of cytokine mRNA levels caused by
      ETEC. The protective effects of ZnO were not due to any antibacterial activity,
      because the viability of ETEC grown in a medium containing ZnO was unaffected. In
      conclusion, ZnO may protect intestinal cells from ETEC infection by inhibiting
      the adhesion and internalization of bacteria, preventing the increase of tight
      junction permeability and modulating cytokine gene expression.

PMID- 14652352
TI  - Conjugated linoleic acids lower the release of eicosanoids and nitric oxide from
      human aortic endothelial cells.
AB  - The objective of this study was to determine the effects of cis-9, trans-11 and
      trans-10, cis-12 CLA on the release of vasoactive eicosanoids and nitric oxide
      (NO) in human aortic endothelial cells. Experiments were conducted in which cells
      were incubated with these fatty acids, and the concentrations of various
      eicosanoids [6-keto prostaglandin (PG) F(1alpha) as a stable product of PGI(2),
      thromboxane (TX) B(2) as a stable product of TXA(2), and PGE(2)] and NO in the
      medium were determined. Cells treated with 50 micro mol/L of either cis-9, trans
      11 or trans-10, cis-12 CLA released less of all of the eicosanoids and NO than
      control cells treated with medium alone (P < 0.05). The ratio between the amounts
      of 6-keto-PGF(1alpha) and that of TXB(2) released did not differ between control
      cells and cells treated with either CLA isomer. Moreover, cells treated with 50
      micro mol/L of cis-9, trans-11 or trans-10, cis-12 CLA had a lower amount of
      arachidonic acid in their phosphatidylethanolamine fraction and a lower mRNA
      concentration and activity of secretory phospholipase A(2) than control cells (P
      < 0.05). These data suggest that eicosanoid formation was impaired by a reduced
      availability of arachidonic acid for the cyclooxygenase pathway. In conclusion,
      this study shows that cis-9, trans 11-CLA and trans-10, cis-12 CLA influence the
      release of various eicosanoids and NO from human aortic endothelial cells. The
      effects observed in this study might be important because eicosanoids and NO
      released from endothelial cells are involved in the regulation of vessel tone and
      platelet aggregation. The results of the present study suggest that both CLA
      isomers had unfavorable effects on endothelial function.

PMID- 14652353
TI  - All-trans-retinoic acid rapidly induces glycine N-methyltransferase in a dose
      dependent manner and reduces circulating methionine and homocysteine levels in
      rats.
AB  - Glycine N-methyltransferase (GNMT) regulates the methyl group supply for S
      adenosylmethionine-dependent transmethylation reactions. Retinoids have been
      shown to perturb methyl group metabolism by increasing the abundance and activity
      of GNMT, thereby leading to the loss of methyl groups. Previous studies used
      pharmacologic doses (30 micro mol/kg body weight) of various retinoids
      administered daily for a total of 10 d. Here, we examined the dose- and time
      dependent relationships between all-trans-retinoic acid (ATRA) administration and
      induction of GNMT, as well as determining additional indices of methyl group and
      folate metabolism. For the dose-response study, rats were administered 0, 1, 5,
      10, 15 or 30 micro mol ATRA/kg body weight for 10 d. For the time-course study,
      rats were given 30 micromol ATRA/kg body weight for 0, 1, 2, 4, or 8 d. A
      significant increase (105%) in GNMT activity was observed with doses as low as 5
      micromol/kg body weight, whereas maximal induction (231%) of GNMT activity was
      achieved at 30 micromol/kg body weight. Induction of hepatic GNMT by ATRA was
      rapid, exhibiting a 31% increase after a single dose (1 d) and achieving maximal
      induction (95%) after 4 d. Plasma methionine and homocysteine concentrations were
      decreased 42 and 53%, respectively, in ATRA-treated rats compared with controls.
      In support of this finding, the hepatic activity of methionine synthase, the
      folate-dependent enzyme required for homocysteine remethylation, was elevated 40%
      in ATRA-treated rats. This work demonstrates that ATRA administration exerts a
      rapid effect on hepatic methyl group, folate and homocysteine metabolism at doses
      that are within the therapeutic range used by humans.

PMID- 14652354
TI  - Fish oil affects pancreatic fat storage, pyruvate dehydrogenase complex activity
      and insulin secretion in rats fed a sucrose-rich diet.
AB  - Rats fed a sucrose-rich diet (SRD) develop hypertriglyceridemia and a marked
      decline in beta cell function. The purpose of this study was to determine whether
      changes in triglyceride concentration and/or altered pyruvate dehydrogenase
      complex (PDHc) activity contribute to the beta cell dysfunction, and to analyze
      the effect of dietary fish oil on the altered patterns of insulin secretion and
      peripheral insulin resistance. Rats were fed an SRD for 210 d. One-half of the
      rats continued consuming the SRD until d 270. The other half received an SRD in
      which fish oil (FO) was partially substituted for corn oil until d 270. A group
      of rats was fed a control diet (CD) throughout the experiment. The islets of rats
      fed the SRD had a greater triglyceride concentration and lower PDHc activity than
      those fed the CD. Insulin secretion patterns under the stimulus of glucose,
      palmitate or L-arginine were impaired in SRD-fed compared with CD-fed rats. This
      was accompanied by peripheral insulin resistance, mild hyperglycemia, a sharp
      increase of plasma triglyceride and free fatty acid levels and greater epididymal
      and retroperitoneal fat weights. FO normalized and/or improved these variables.
      Our results indicate that the increased fat storage and decreased PDHc activity
      in the beta cells play a key role in the abnormal insulin secretion of rats
      chronically fed an SRD. This is consistent with the reversion of these
      alterations by dietary FO.

PMID- 14652355
TI  - VLDL metabolism in rats is affected by the concentration and source of dietary
      protein.
AB  - The present study was designed to determine if changes in dietary protein level
      and source are related to changes in VLDL lipid concentrations and VLDL binding
      by hepatic membranes and isolated hepatocytes. Male Wistar rats were fed
      cholesterol-free diets containing 10, 20 or 30 g/100 g casein or highly purified
      soybean protein for 4 wk. Hepatic, plasma and VLDL lipids, VLDL apo B-100 and
      VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane were
      determined. Increasing casein or soybean protein level (from 10 to 30 g/100 g) in
      the diet increased VLDL apo B-100, indicating an increase in the number of VLDL
      particles. VLDL uptake by isolated hepatocytes and VLDL binding to hepatic
      membrane increased when the protein level increased from 10 to 20 g/100 g in the
      diet and decreased with 30 g/100 g protein, regardless of protein type. The
      dietary protein source did not affect plasma total cholesterol concentrations at
      any protein level. Feeding 20 g/100 g soybean protein compared with casein
      lowered plasma triglyceride concentrations and VLDL number as measured by
      decreased VLDL-protein, -phospholipid, -triglyceride, -cholesterol and -apo B
      100. VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane
      were higher in rats fed soybean protein than those fed casein. The higher VLDL
      uptake could be responsible for the hypotriglyceridemia in rats fed soybean
      protein.

PMID- 14652356
TI  - Folate status response to controlled folate intake is affected by the
      methylenetetrahydrofolate reductase 677C-->T polymorphism in young women.
AB  - This study was designed to evaluate the effect of the methylenetetrahydrofolate
      reductase (MTHFR) 677C-->T polymorphism on folate and homocysteine response in
      non-Hispanic women consuming a low folate diet followed by a diet providing the
      Recommended Dietary Allowance (RDA) for folate. Women (aged 20-30 y old) with
      either the TT (n = 19) or CC (n = 22) MTHFR 677C-->T genotype participated in a
      folate depletion-repletion study (7 wk, 115 microg dietary folate equivalents
      (DFE)/d; 7 wk, 400 microg DFE/d). Overall serum folate decreased (P < 0.0001)
      during depletion and increased (P < 0.0001) during repletion with lower (P =
      0.03) postdepletion serum folate in women with the TT versus CC genotype. Folate
      status was low (serum folate < 13.6 nmol/L) in more women with the TT (59%)
      compared with the CC genotype (15%) postdepletion. Red blood cell folate for all
      subjects decreased during depletion (P < 0.0001) and repletion (P = 0.02) with
      lower (P = 0.04) red blood cell folate in women with the TT compared with the CC
      genotype postrepletion. Homocysteine increased (P < 0.0001) for both genotype
      groups postdepletion and decreased (P = 0.02) postrepletion for the CC genotype
      group only. Homocysteine concentrations tended to be higher (P = 0.09) in the TT
      versus CC genotype group postdepletion and postrepletion. These data suggest that
      the MTHFR 677C-->T polymorphism negatively affects the folate and homocysteine
      response in women consuming low folate diets followed by repletion with the RDA.
      These results may be important when evaluating the impact of the MTHFR 677C-->T
      polymorphism in countries in which low folate diets are chronically consumed.

PMID- 14652357
TI  - RNA polymerase II association with the phosphoenolpyruvate carboxykinase (PEPCK)
      promoter is reduced in vitamin A-deficient mice.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) gene expression is decreased in vitamin
      A-deficient (VAD) mice. However, the underlying molecular mechanism at the PEPCK
      promoter that contributes to this alteration in gene expression remains
      unexplained and thus serves as the basis for our investigation in this report.
      Using liver from vitamin A-sufficient (VAS) and VAD mice in the chromatin
      immunoprecipitation (ChIP) assay, we determined that histones H3 and H4 were in
      the acetylated or active state in VAS mice at each of the three retinoic acid
      response elements (RARE1, RARE2 and RARE3) of the PEPCK promoter. The same
      acetylation pattern was seen in VAD mice, but with relatively lower levels of
      acetylated H3 and H4 bound at the region encompassing PEPCK RARE1/RARE2. In ChIP
      assays conducted with an antibody to RNA polymerase II (RNA Pol II), the
      association of RNA Pol II with PEPCK RARE1/RARE2 was significantly decreased in
      vitamin A deficiency. The reduction in RNA Pol II association is indicative of an
      interruption in the direct interactions of RNA Pol II with the PEPCK promoter,
      with general transcription factors and/or with coregulator molecules that
      contribute to the activation of the PEPCK gene. These results increase our
      understanding of the molecular basis for decreased PEPCK gene expression in VAD
      mice in vivo and offer additional insight into the regulation of other retinoid
      responsive genes.

PMID- 14652358
TI  - Decreasing dietary sodium while following a self-selected potassium-rich diet
      reduces blood pressure.
AB  - Reducing dietary sodium reduces blood pressure (BP), a major risk factor for
      cardiovascular disease, but few studies have specifically examined the effect on
      BP of altering dietary sodium in the context of a high potassium diet. This
      randomized, crossover study compared BP values in volunteer subjects self
      selecting food intake and consuming low levels of sodium (Na+; 50 mmol/d) with
      those consuming high levels of sodium (> or =120 mmol/d), in the context of a
      diet rich in potassium (K+). Sodium supplementation (NaSp) produced the
      difference in Na+ intake. Subjects (n = 108; 64 women, 44 men; 16 on
      antihypertensive therapy) had a mean age of 47.0 +/- 10.1 y. Subjects were given
      dietary advice to achieve a low sodium (LS) diet with high potassium intake (50
      mmol Na+/d, >80 mmol K+/d) and were allocated to NaSp (120 mmol Na+/d) or placebo
      treatment for 4 wk before crossover. The LS diet decreased urinary Na+ from
      baseline, 138.7 +/- 5.3 mmol/d to 57.8 +/- 3.8 mmol/d (P < 0.001). The NaSp
      treatment returned urinary Na+ to baseline levels 142.4 +/- 3.7 mmol/d. Urinary
      K+ increased from baseline, 78.6 +/- 2.3 to 86.6 +/- 2.1 mmol/d with the LS diet
      and to 87.1 +/- 2.1 mmol/d with NaSp treatment (P < 0.001). The LS diet reduced
      home systolic blood pressure (SBP) by 2.5 +/- 0.8 mm Hg (P = 0.004), compared
      with the NaSp treatment. Hence, reducing Na+ intake from 140 to 60 mmol/d
      significantly decreased home SBP in subjects dwelling in a community setting who
      consumed a self-selected K+-rich diet, and this dietary modification could assist
      in lowering blood pressure in the general population.

PMID- 14652359
TI  - Incorporating dairy foods into low and high fat diets increases the postprandial
      cholecystokinin response in men and women.
AB  - The postprandial period is a dynamic state of hormone and lipoprotein metabolism
      that can be influenced by dietary composition. The objective of this study was to
      determine whether the source of dietary fat [dairy (D) vs. nondairy (ND)] would
      modify the lipemic, insulin and cholecystokinin (CCK) response to high or low fat
      meals. Men and women (n = 24) consumed 4 test meals with a similar
      polyunsaturated:saturated (P:S; 0.12:1) fat ratio. The diets were high (38%
      energy) or low (20% energy) in fat, with or without fat from dairy sources. CCK
      responses were greater after consumption of meals containing D than ND, and for
      high compared with low fat meals. Women had higher CCK responses than men and
      were more sensitive to the differences in dietary treatments. Consumption of low
      fat meals resulted in greater insulin responses than high fat meals. However,
      after consumption of the low fat meals, the insulin response of D was about half
      of the ND response; no differences in insulin response were detected after the
      high fat meals. Triacylglyceride response was influenced primarily by the fat
      content of the diet. Consumption of dairy products containing fat was associated
      with an enhanced CCK response, which may have implications for the regulation of
      food intake. Blunting glucose and insulin response in low fat meals containing
      fat from dairy products may be useful for glycemic control.

PMID- 14652360
TI  - Stearic acid absorption and its metabolizable energy value are minimally lower
      than those of other fatty acids in healthy men fed mixed diets.
AB  - Compared with other saturated fatty acids, stearic acid appears to have different
      metabolic effects with respect to its impact on risk for cardiovascular disease.
      These differences may in part reflect biologically important differences in
      absorption. This study was designed to compare the absorption and the
      metabolizable energy value of stearic acid with other fatty acids from mixed
      diets fed to healthy humans. Healthy men (n = 11) were fed four diets with
      multiple fat sources that contained approximately 15% of energy (en%) from
      protein, 46 en% from carbohydrate and 39 en% from fat with 8 en% substitution
      across diets of the following: trans monoenes, oleic acid, saturated fatty acids
      (lauric + myristic + palmitic) or stearic acid fed as triacylglycerides. Fats
      were incorporated into mixed diets comprised of foods typically consumed in the
      United States. After a 14-d adaptation period, volunteers collected all feces for
      7 d. Across diets, absorption of stearic acid (94.1 +/- 0.2%) was lower (P <
      0.0002) than that of palmitic acid (97.3 +/- 0.2%) and higher than generally
      reported. Absorption of lauric, myristic, oleic, linoleic and trans 18:1 monoenes
      did not differ from each other (>99%) but was higher than that of stearic and
      palmitic acids (P < 0.001). Metabolizable energy values were similar for all
      fatty acids. Although absorption of palmitic and stearic acids was affected by
      diet treatment, the magnitudes of the differences were small and do not appear to
      be biologically important, at least in terms of lipoprotein metabolism. On the
      basis of these results, reduced stearic acid absorption does not appear to be
      responsible for the differences in plasma lipoprotein responses to stearic acid
      relative to other saturated or unsaturated fatty acids.

PMID- 14652361
TI  - Low dose betaine supplementation leads to immediate and long term lowering of
      plasma homocysteine in healthy men and women.
AB  - High plasma homocysteine is a risk for cardiovascular disease and can be lowered
      through supplementation with 6 g/d of betaine. However, dietary intake of betaine
      is approximately 0.5-2 g/d. Therefore, we investigated whether betaine
      supplementation in the range of dietary intake lowers plasma homocysteine
      concentrations in healthy adults. Four groups of 19 healthy subjects ingested
      three doses of betaine or placebo daily for 6 wk. A methionine loading test was
      performed during run in, on d 1 of betaine supplementation, and after 2 and 6 wk
      of betaine supplementation. Fasting plasma homocysteine after 6-wk daily intakes
      of 1.5, 3 and 6 g of betaine was 12% (P < 0.01), 15% (P < 0.002) and 20% (P <
      0.0001) less than in the placebo group, respectively. Furthermore, the increase
      in plasma homocysteine after methionine loading on the 1st d of betaine
      supplementation was 16% (P < 0.06), 23% (P < 0.008) and 35% (P < 0.0002) less
      than in the placebo group, respectively, and after 6 wk of supplementation was
      23% (P < 0.02), 30% (P < 0.003) and 40% (P < 0.0002) less, respectively. Thus,
      doses of betaine in the range of dietary intake reduce fasting and postmethionine
      loading plasma homocysteine concentrations. A betaine-rich diet might therefore
      lower cardiovascular disease risk.

PMID- 14652362
TI  - Low hemoglobin level is a risk factor for postpartum depression.
AB  - The role of maternal anemia in the development of postpartum depression (PPD) is
      unclear. PPD is a serious disorder that may negatively affect the physical and
      emotional health of a new mother and her infant. Although psychosocial factors
      that increase the risk of developing PPD are known, few studies have identified
      physiologic factors that predispose a woman to PPD. New mothers were visited at
      home on d 7, 14 and 28 after an uncomplicated labor and delivery. Hemoglobin (Hb)
      concentration was measured via finger-prick blood at each visit, and the women
      completed the Center for Epidemiological Studies-Depressive Symptomatology Scale
      (CES-D) on d 28. There was a negative correlation between Hb concentration on d 7
      postpartum and depressive symptoms on d 28 (r = -4.26; P = 0.009). CES-D scores
      (means +/- SEM) on d 7 of women with normal Hb levels > 120 g/L (12 g/dL) were
      significantly lower (6.90 +/- 1.04) than those of women with Hb levels < or = 120
      g/L (12 g/dL) [16.36 +/- 3.34; t(35) = -3.632, P = 0.001]. Thus, women suffering
      early postpartum anemia may be at increased risk of developing PPD.

PMID- 14652363
TI  - Iron deficiency is unacceptably high in refugee children from Burma.
AB  - Iron-deficiency anemia (IDA) in refugees is reported to be among the major
      medical problems worldwide. Because food rations are typically inadequate in
      iron, long-term reliance is a key predictor of anemia among displaced people.
      Comprehensive nutritional assessments of refugee children from Burma have not
      previously been completed. Refugee children aged 6-59 mo were studied to
      determine 1) the prevalences of anemia, iron deficiency (ID) and IDA and 2) the
      factors associated with anemia and ID. Cluster sampling in three camps and
      convenience sampling in two additional camps were used. Hemoglobin (Hb) levels
      were measured and micro mol zinc protoporphyrin/mol heme were determined in 975
      children. Logistic regression analyses (95% CI) determined predictors of anemia
      and ID. The prevalences of IDA, anemia and ID in these refugee children were
      64.9, 72.0 and 85.4%, respectively. Predictors of anemia included young age (P <
      0.001), food ration lasting <1 mo (P = 0.001), daily consumption of dietary iron
      inhibitors (P < 0.05), weight-for-height Z-score of <-2 (P < 0.05), male gender
      (P < 0.05) and uneducated father (P < 0.001). Predictors of ID were young age (P
      < 0.001) and recently reported illness (P < 0.05). Laboratory tests confirmed
      that anemia and ID are major health problems among these refugee children and
      that ID is the leading cause of anemia. A comprehensive nutrition and public
      health-focused approach to combating anemia and ID is essential. Following the
      presentation of results to policy makers, the improvement of the micronutrient
      content of rations has been initiated.

PMID- 14652364
TI  - Simultaneous weekly supplementation of iron and zinc is associated with lower
      morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi
      infants.
AB  - Given the high prevalence of micronutrient deficiencies and infectious diseases
      in infants in developing countries, an evaluation of the efficacy of different
      micronutrient formulations on infant morbidity is a priority. The efficacy of
      weekly supplementation of four different micronutrient formulations on diarrhea
      and acute lower respiratory infection (ALRI) morbidity was evaluated in
      Bangladeshi infants. In a double-blind, randomized, controlled community trial,
      799 infants aged 6 mo were randomly assigned to one of the following 5 groups: 1)
      20 mg elemental iron with 1 mg riboflavin, 2) 20 mg elemental zinc with 1 mg
      riboflavin, 3) 20 mg iron and 20 mg zinc with 1 mg riboflavin, 4) a micronutrient
      mix (MM) containing 20 mg iron, 20 mg zinc, 1 mg riboflavin along with other
      minerals and vitamins and 5) a control treatment, 1 mg riboflavin only. Health
      workers visited each infant weekly until age 12 mo to feed the supplement and to
      collect data on diarrhea and ALRI morbidity. Hemoglobin, serum ferritin and serum
      zinc levels of a sample of infants were measured at 6 and 12 mo. Compared with
      the control group, at 12 mo, serum ferritin levels were higher in the iron + zinc
      group, and serum zinc levels were higher in the zinc and iron + zinc groups.
      Simultaneous supplementation with iron + zinc was associated with lower risk of
      severe diarrhea, 19% lower in all infants and 30% lower in less well-nourished
      infants with weight-for-age Z-score below -1. Iron + zinc supplementation was
      also associated with 40% lower risk of severe ALRI in less well-nourished
      infants. MM supplementation was associated with a 15% higher risk of diarrhea in
      all infants and 22% higher risk in less well-nourished infants. Intermittent
      simultaneous supplementation with iron + zinc seems promising; it will be useful
      to determine whether higher doses would provide greater benefits.

PMID- 14652365
TI  - Understanding the experience of household food insecurity in rural Bangladesh
      leads to a measure different from that used in other countries.
AB  - This research aimed to gain in-depth understanding of the experience of household
      food insecurity in rural Bangladesh and to develop a direct measure of it from
      this understanding. Using naturalistic, emergent inquiry, in-depth interviews
      were conducted with 21 rural women living in diverse situations using a
      semistructured interview guide. Two analytic strategies classified households on
      food insecurity and elicited themes that were the basis for classification.
      Survey questions were developed to capture themes, and were revised after review,
      field testing, and ranking and pile-sorting exercises. Four gradations of
      severity of food insecurity resulted, based on nine themes: meals, cooking, rice,
      fish, perishable foods, snacks, festival food, other expenditures and management
      strategies. The emergent conceptualization of food insecurity differs from that
      found from naturalistic research in other countries. The developed food
      insecurity measure has 11 questions. This research affirms the value of gaining
      in-depth understanding of household food insecurity. In many situations, this
      approach, rather than translating questions developed elsewhere, may best lead to
      suitable experience-based measures of food insecurity.

PMID- 14652366
TI  - Response of plasma leptin concentration to jugular infusion of glucose or lipid
      is dependent on the stage of lactation of Holstein cows.
AB  - In this study we investigated the hormonal and metabolite responses to
      isoenergetic jugular infusions of glucose or lipid in early- and late-lactation
      Holstein cows. Six Holstein cows were used in a replicated Latin square design
      with jugular infusions of either 1) control (CON; saline), 2) glucose (GLU; 50%
      dextrose) or 3) lipid (LIP; 20% Intralipid). Treatments did not affect dry matter
      intake, with the exception of a hypophagic effect of LIP in late lactation. The
      GLU-induced hyperglycemia and hyperinsulinemia were greater in late-lactation
      than in early-lactation cows. The GLU treatment did not affect plasma leptin and
      insulin-like growth factor-1 (IGF-1) concentrations in early-lactation cows, but
      it increased them in late-lactation cows. The LIP treatment did not affect plasma
      leptin, insulin and IGF-1 concentrations in early-lactation cows, despite a
      marked LIP-induced increase in plasma nonesterified fatty acid and beta
      hydroxybutyrate concentrations and a reduction in growth hormone (GH)
      concentration. Compared with the delayed leptin response to GLU, the stimulatory
      effect of LIP on leptin secretion in late-lactation cows was relatively rapid and
      occurred in the absence of any significant changes in plasma insulin, IGF-1 or
      GH. We propose that insulin-mediated glucose metabolism may be involved in the
      stimulatory effects of glucose on leptin secretion in late-lactation animals but
      that the stimulatory effects of lipid are independent of insulin or IGF-1. In
      early-lactation animals a strong inhibitory effect of GH on leptin expression and
      release, in addition to low adipose reserves and/or energy balance, might
      override any short-term stimulatory effect of glucose or lipid on leptin
      secretion.

PMID- 14652367
TI  - Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following
      oral administration to mice.
AB  - Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea
      (Camellia sinensis), has shown cancer preventive activity in animal models. The
      bioavailability of EGCG in the most commonly used animal species, mice, is poorly
      understood. Moreover, the pharmacokinetic parameters of EGCG have not been
      reported previously in mice. Here we report that after administration of EGCG
      intravenously at 21.8 micro mol/kg or intragastrically at 163.8 micro mol/kg, the
      peak plasma levels of EGCG in male CF-1 mice were 2.7 +/- 0.7 and 0.28 +/- 0.08
      micro mol/L, respectively. EGCG was present mainly (50-90%) as the glucuronide.
      The plasma bioavailability of EGCG after intragastric administration was higher
      than previously reported in rats (26.5 +/- 7.5% vs. 1.6 +/- 0.6%). The conjugated
      EGCG displayed a shorter t(1/2) (82.8-211.5 vs 804.9-1102.3 min) than
      unconjugated EGCG (P < 0.01, Student's t test). EGCG was present in the
      unconjugated form in the lung, prostate and other tissues at levels of 0.31-3.56
      nmol/g after intravenous administration. Although intragastric administration
      resulted in lower levels in most tissues compared with intravenous administration
      (e.g., 0.006 +/- 0.004 vs. 2.66 +/- 1.0 nmol/g in the lung), the levels in the
      small intestine and colon were high at 45.2 +/- 13.5 and 7.86 +/- 2.4 nmol/g,
      respectively. This is the first report of the pharmacokinetic parameters of EGCG
      in mice. Such information provides a basis for understanding the bioavailability
      of EGCG in mice and should aid in understanding the cancer preventive activity of
      EGCG.

PMID- 14652368
TI  - Anthocyanins are efficiently absorbed from the stomach in anesthetized rats.
AB  - After consumption, anthocyanins are rapidly absorbed as glycosides. Their rapid
      appearance in plasma could result from absorption through the gastric wall. The
      aim of this study was to evaluate the fate of anthocyanins in the stomach.
      Absorption of purified anthocyanins (14 micromol/L) as well as blackberry 14 and
      750 micromol/L) and bilberry (88 micromol/L) anthocyanins was compared after in
      situ gastric administration for 30 min. A high proportion (approximately 25%) of
      anthocyanin monoglycosides (glucoside or galactoside) was absorbed from the
      stomach, whereas absorption of cyanidin 3-rutinoside was lower. Bilberry
      anthocyanins were also efficiently absorbed, but absorption varied greatly (19
      37%) according to the anthocyanin structure; delphinidin glycosides were the most
      absorbed. When a high concentration of blackberry anthocyanins (750 micromol/L)
      was injected into the gastric lumen, the percentage of cyanidin 3-glucoside (Cy 3
      glc) absorption was lower than after administration of a low concentration (14
      micromol/L). After administration of this high concentration, blackberry
      anthocyanins were observed in plasma from gastric vein and aorta, whereas neither
      aglycones nor metabolites were detected. Analysis of bile samples revealed that
      Cy 3-glc appeared in bile after as little as 20 min. Peonidin 3-glucoside (the
      methylated form of Cy 3-glc) as well as unknown anthocyanin metabolites were also
      observed in bile. Thus, this study demonstrated that anthocyanin glycosides were
      quickly and efficiently absorbed from the stomach and rapidly excreted into bile
      as intact and metabolized forms.

PMID- 14652369
TI  - Study of diet-induced changes in lipoprotein metabolism in two strains of Golden
      Syrian hamsters.
AB  - The objective of this study was to characterize two strains of Golden-Syrian
      hamsters for use in the study of diet-induced changes in lipoprotein metabolism.
      In Experiment 1, the time course and response to dietary saturated fat was
      investigated for serum lipoprotein profiles and aortic lesion formation in Golden
      Syrian hamsters from Charles River Laboratories, Wilmington, MA (CR) and Bio
      Breeders, Watertown, MA (F(1)B). Hamsters were fed a nonpurified diet containing
      10 g/100 g saturated fat and 0.1 g/100 g dietary cholesterol. After 12 wk, CR
      hamsters had significantly lower serum total and non-HDL cholesterol (TC and nHDL
      C) levels, but higher aortic cholesteryl ester (CE) than the F(1)B hamsters (P <
      0.05). In Experiment 2, CR hamsters were fed a nonpurified diet containing 10
      g/100 g saturated fat and 0.1, 0.5 or 1 g/100 g dietary cholesterol. After 10 wk
      of dietary intervention, TC and nHDL-C levels were significantly higher in the
      0.5 and 1.0 g/100 g cholesterol groups than in the 0.1 g/100 g cholesterol group.
      These levels declined after 20 wk of dietary intervention in all groups,
      potentially reflecting the toxic effect of high cholesterol intakes. CR hamsters
      fed a 10 g/100 g saturated fat containing 0.1 g/100 g dietary cholesterol for 10
      wk appear to be a good model for investigating diet-induced change in plasma
      lipids.

PMID- 14652370
TI  - [14C]-lycopene and [14C]-labeled polar products are differentially distributed in
      tissues of F344 rats prefed lycopene.
AB  - Epidemiologic evidence suggests a possible role for lycopene-rich foods in the
      prevention of prostate cancer and cardiovascular disease. Despite active research
      in disease reduction, there is a paucity of information on the absorption,
      biodistribution and metabolism of lycopene. The aim of this study was to evaluate
      the biodistribution of 14C-lycopene (specific activity, 1.83 microCi/mg) and 14C
      labeled products after an oral dose of 22 microCi of 14C-lycopene in male rats
      that had been prefed a lycopene-containing diet (0.25 g lycopene/ kg diet) for 30
      d. The percentage of 14C excreted in feces and urine over the 168 h was 68%.
      Quantitatively, serum 14C levels were maintained between 3 and 24 h then
      decreased at 72 h (P < 0.05). At all time points the majority of tissue 14C was
      in the liver (approximately 72%), although total hepatic 14C decreased after 24
      h. In a comparison of the extrahepatic tissue at 168 h, the 14C was greatest in
      adipose tissue followed by spleen and then adrenal; approximately 80% of the 14C
      in the liver was in the cis and all-trans configuration at all time points. At 3
      h, the 14C in seminal vesicles was primarily in the all-trans plus 5-cis forms
      (70%), but by 168 h, 55% of 14C was present as 14C-polar products. Despite the
      presence of unlabeled lycopene in the prostate, the primary 14C form was in 14C
      polar products (67-92%), even at 3 h. The percentage and amount of 14C-polar
      products in the dorsolateral prostate lobe increased from 3 to 24 h and then
      reached a plateau. The data suggest that lycopene may be metabolized differently
      among tissues in rats prefed lycopene.

PMID- 14652371
TI  - Plasma leptin is regulated predominantly by nutrition in preruminant lambs.
AB  - In juvenile and mature animals, the plasma concentration of leptin is regulated
      by adiposity and nutrition. However, the timing of these influences on plasma
      leptin, and their relative importance in early postnatal life, are unknown. We
      investigated these plasma leptin influences in sheep, a species characterized
      during fetal life by leanness and insensitivity of leptin to variation in
      maternal nutrition. Small and large neonatal lambs were randomly assigned to
      either a diet sustaining an average daily weight gain (ADG) of 148 g/d (Low
      plane) or ate ad libitum a diet sustaining an ADG of 337 g/d (High plane). A
      subset of animals were slaughtered at 7.5, 10, 15 and 20 kg of body weight. Birth
      size had no effect on plasma leptin concentrations and adiposity at birth or at
      later times. Plasma leptin concentrations increased within 6 d of birth in the
      High plane lambs (P < 0.01) and continued to rise over time. In contrast, plasma
      leptin concentrations never changed in the Low plane lambs despite increasing
      adiposity. The positive association between plasma leptin concentration and
      adiposity was greater in the High plane than in the Low plane lambs, suggesting
      an independent effect of nutrition. Consistent with this finding, lipid accretion
      rates, a variable that is mostly independent of adiposity, was a strong predictor
      of plasma leptin concentrations only in the High plane lambs (R(2) = 0.77, P <
      0.01). A positive association between plasma insulin and leptin developed over
      time in the High plane lambs (R(2) = 0.75, P < 0.01 on d 40), but was not seen in
      the Low plane lambs. These data indicate that both nutrition and adiposity
      regulate plasma leptin synthesis in early postnatal life, but in contrast to
      adulthood, the effects of nutrition appear to be predominant.

PMID- 14652372
TI  - Serum vitamin A esters are high in captive rhesus (Macaca mulatta) and marmoset
      (Callithrix jacchus) monkeys.
AB  - We showed previously that hepatic vitamin A concentrations of captive rhesus
      monkeys (Macaca mulatta) are subtoxic to toxic, with livers exhibiting stellate
      cell hypertrophy and hyperplasia. Although marmoset (Callithrix jacchus) livers
      are also high in vitamin A, no stellate cell irregularities were observed. To
      further characterize the effects of high dietary vitamin A from preformed
      sources, stored serum samples were analyzed from monkeys used for biomedical
      research and housed at the Wisconsin Primate Research Center. The monkeys had
      been fed commercially available monkey diets, providing vitamin A (as retinyl
      acetate) at levels exceeding NRC recommendations by a factor of four. The serum
      from both rhesus and marmoset monkeys had total serum vitamin A (retinol, retinyl
      esters and metabolites) within the expected range for both species, i.e., 1.44 +/
      0.34 and 1.41 +/- 0.72 micromol/L serum for rhesus and marmoset monkeys,
      respectively. However, high serum retinyl ester concentrations as a percentage of
      total serum vitamin A were present in both species, 12 +/- 5.1% (range, 5.5-23%)
      for rhesus and 27 +/- 14% (range, 10-57%) for the marmosets. Serum retinol
      concentrations were normal, i.e., 1.21 +/- 0.28 (rhesus) and 0.92 +/- 0.43
      micromol/L (marmoset), compared with published values.

PMID- 14652373
TI  - Ingestion of difructose anhydride III and voluntary running exercise
      independently increase femoral and tibial bone mineral density and bone strength
      with increasing calcium absorption in rats.
AB  - Difructose anhydride III (DFAIII), a nondigestible disaccharide, promotes
      intestinal calcium absorption. Exercise-induced mechanical stimuli are essential
      for bone growth. In the present study, we examined the effects of consuming
      DFAIII and voluntary running exercise on calcium absorption and bone
      characteristics using male Sprague-Dawley rats (4 wk old). The study was designed
      in a 2 x 2 factorial arrangement with two conditions (sedentary or exercised) and
      two diets [AIN-93G diet with or without DFAIII (30 g/kg diet)]. Both consuming
      DFAIII and running exercise increased net calcium absorption, and the effects of
      DFAIII and exercise were additive. Both consuming DFAIII and exercise also
      increased femoral variables such as calcium content and total bone mineral
      density (BMD); however, only consuming DFAIII increased bone strength in the
      femur. Conversely, running exercise augmented tibial calcium content, total BMD
      and bone strength, but consuming DFAIII did not. We conclude that consuming
      DFAIII and running exercise additively enhance calcium absorption and
      differentially stimulate femoral and tibial BMD and mechanical properties in
      rats.

PMID- 14652374
TI  - The position of rumenic acid on triacylglycerols alters its bioavailability in
      rats.
AB  - The metabolic fate of rumenic acid (9cis,11trans-octadecenoic acid) related to
      its position on the glycerol moiety has not yet been studied. In the present
      work, synthetic triacylglycerols (TAG) esterified with oleic and rumenic acids
      were prepared. Rats were force-fed synthetic dioleyl monorumenyl glycerol with
      (14)C labeled rumenic acid in the internal (sn-2) or in the external position (sn
      1 or sn-3). Rats were then placed in metabolic cages for 16 h. At the end of the
      experiment, the radioactivity in tissues, carcass and expired CO(2) was measured.
      Rumenic acid that was esterified at the external positions on the TAG was better
      absorbed and oxidized to a greater extent than when esterified at the internal
      position. The fatty acid from the 2-TAG form was also better incorporated into
      the rat carcass. In the liver, rumenic acid appeared mainly in TAG (50%) and to a
      lesser extent in phospholipids (33%) whatever its dietary form. Moreover,
      analyses of lipids from Camembert cheese and butter revealed that rumenic acid
      was located mainly on the sn-1 or sn-3 positions (74%). Taken together, these
      data suggest that rumenic acid from dairy fat may be well absorbed and used
      extensively for energy production.

PMID- 14652375
TI  - Dietary cysteine reduces the methionine requirement by an equal proportion in
      both parenterally and enterally fed piglets.
AB  - The sulfur amino acids (SAA), methionine and cysteine, are normally supplied in a
      50:50 ratio in the oral diet of pigs. In contrast, cysteine is not included in
      any appreciable amounts in parenteral solutions due to its instability in
      solution. Cysteine can replace part of the methionine requirement, but is not
      required when methionine is supplied at a level that meets the entire SAA
      requirement. However, the role of the gut on cysteine sparing has not been
      investigated. In the present study, the enteral and parenteral methionine
      requirement was determined, with excess dietary cysteine, by using the indicator
      amino acid oxidation (IAAO) technique. Piglets [n = 28, 2 d, 1.65 +/- 0.014 kg
      (SE)] were fed elemental diets containing adequate energy, phenylalanine and
      excess tyrosine, with varied methionine concentrations and excess cysteine [0.55
      g/(kg. d)]. Diets were infused continuously via intravenous (parenteral) or
      gastric (enteral) catheters. Phenylalanine oxidation was determined during a
      primed, constant infusion of L-[1-(14)C]-phenylalanine, by measuring expired
      (14)CO(2) and plasma specific radioactivity (SRA) of phenylalanine. For both the
      parenteral and enteral groups, phenylalanine oxidation (% of dose) decreased
      linearly (P < 0.01) as methionine intake increased and then became low and
      unchanging. Using breakpoint analysis, the methionine requirement was estimated
      to be 0.25 and 0.18 g/(kg. d) for enteral and parenteral feeding, respectively.
      These data show that the parenteral methionine requirement is approximately 70%
      of the enteral requirement when measured in the presence of excess dietary
      cysteine (P < 0.05). A comparison with our previous studies in which methionine
      was the only source of sulfur amino acids shows that the addition of dietary
      cysteine reduces the methionine requirement by approximately 40% in both
      enterally and parenterally fed neonatal piglets. Therefore, dietary cysteine is
      equally effective in sparing dietary methionine whether fed enterally or
      parenterally.

PMID- 14652376
TI  - The smallest vertebrate, teleost fish, can utilize synthetic dipeptide-based
      diets.
AB  - In vitro studies of brush-border intestinal transport of dipeptides and
      cytoplasmic hydrolysis in fish suggest that these processes could be key
      mechanisms in the absorption and utilization of nutrients for growth. However, in
      vivo experimentation to study the nutritional importance of these processes was
      needed. We compared three dietary formulations based on free, peptide and protein
      sources of amino acids. Our results were the first to show that a synthetic
      dipeptide (PP)-based diet could support growth in the early stages of ontogenesis
      of a teleost fish, rainbow trout (Oncorhynchus mykiss), whereas a free amino acid
      (FAA)-based diet failed. We found that fish fed an FAA-based diet had an
      increased rate of ammonia excretion [1.78 +/- 0.19 mmol NH(3)-N/(kg body wt.h)],
      compared with fish fed a PP-based diet [1.25 +/- 0.07 mmol NH(3)-N/(kg body
      wt.h)], suggesting that deamination is involved in the metabolism of dietary FAA.
      Teleost fish are known to obtain a high proportion of total energy from protein,
      compared with higher vertebrates. However, we found that feeding trout alevins a
      PP-based diet increased postprandial oxygen consumption for 2 to 24 h, whereas
      other treatments decreased 24-h postprandial metabolism. This may indicate that
      peptide metabolism is less efficient than protein metabolism. Juvenile rainbow
      trout differed from alevins in their response to FAA- and PP-based diets. These
      observations strongly suggest that intestinal dietary peptide transport and
      hydrolysis could support protein synthesis and growth in vertebrates that respond
      poorly to FAA-based diets. We conclude that nutrient administration may be
      improved by manipulating dietary peptide composition and peptide/protein ratios,
      leading to better utilization of synthetic peptides, with nutritional and
      therapeutic implications for all vertebrates.

PMID- 14652377
TI  - The effect of eicosapentaenoic acid on rat lymphocyte proliferation depends upon
      its position in dietary triacylglycerols.
AB  - Animal and human studies have shown that greatly increasing the amount of fish
      oil [rich in long-chain (n-3) PUFA] in the diet can decrease lymphocyte
      functions. The effects of a more modest provision of long-chain (n-3) PUFA and
      whether eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) have the
      same effects as one another are unclear. Whether the position of 20:5 or 22:6 in
      dietary triacylglycerols (TAG) influences their incorporation into immune cells
      and their subsequent functional effects is not known. In this study, male
      weanling rats were fed for 6 wk one of 9 diets that contained 178 g lipid/kg and
      that differed in the type of (n-3) PUFA and in the position of these in dietary
      TAG. The control diet contained 4.4 g alpha-linolenic acid (18:3)/100 g total
      fatty acids. In the other diets, 20:5 or 22:6 replaced a portion (50 or 100%) of
      18:3, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were
      significant dose-dependent increases in the proportion of 20:5 or 22:6 in spleen
      mononuclear cell phospholipids when 20:5 or 22:6 was fed. These increases were at
      the expense of arachidonic acid and were largely independent of the position of
      20:5 or 22:6 in dietary TAG. Spleen lymphocyte proliferation increased dose
      dependently when 20:5 was fed in the sn-1(3) position of dietary TAG. There were
      no significant differences in interleukin-2, interferon-gamma or interleukin-10
      production among spleen cells from rats fed the different diets. Prostaglandin
      E(2) production by spleen mononuclear cells was decreased by inclusion of either
      20:5 or 22:6 in the diet in the sn-1(3) position. Thus, incorporation of 20:5 or
      22:6 into spleen mononuclear cell phospholipids is not influenced by the position
      in dietary TAG. However, the pattern of incorporation may be influenced, and
      there are some differential functional effects of the position of long-chain (n
      3) PUFA in dietary TAG. A moderate increase in the intake of 20:5 at the sn-1(3)
      position of dietary TAG increases lymphocyte proliferation.

PMID- 14652378
TI  - Zinc-deficient rats have fewer recent thymic emigrant (CD90+) T lymphocytes in
      spleen and blood.
AB  - It has been hypothesized that increased expression of the signaling protein
      p56(lck) disrupts maturation of T lymphocytes, leading to the lymphopenia
      associated with dietary zinc deficiency and malnutrition. Our objective was to
      examine p56(lck) protein levels, flow cytometric markers of T cell development
      (CD4, CD8, TCRalphabeta, TCRgammadelta and CD90) and absolute cell numbers in
      thymus, spleen and blood of zinc-deficient (ZD), diet-restricted (DR) and control
      (CTL) rats. Recent thymic emigrant (CD90+) T lymphocytes were also investigated
      after dietary repletion. P56(lck) protein levels were one- to twofold greater in
      thymocytes than splenocytes, and ZD rats had more thymocyte p56(lck) protein than
      CTL rats. In the thymus and blood, the proportions of T lymphocyte subpopulations
      (CD4-CD8-, CD4+CD8+ and CD4+CD- or CD4-CD8+) were unchanged, except for a higher
      percentage of TCRalphabeta+CD-CD8+ thymocytes in ZD rats. The 15-29% fewer CD90+
      T cells in the blood and spleen of ZD rats were reversed after dietary repletion
      for 7 and 23 d, respectively. In summary, T-cell numbers were proportional to
      thymus and spleen weights and unaltered per unit blood volume, despite elevated
      thymocyte p56(lck) protein in ZD rats. In zinc deficiency, the decreased
      percentages of CD90+ cells in the blood and spleen could adversely affect the T
      cell repertoire.

PMID- 14652379
TI  - Exclusive breastfeeding of healthy term infants for at least 6 weeks improves
      neurological condition.
AB  - To investigate the minimal duration of exclusive breastfeeding for optimal
      neurological outcome, we assessed the quality of general movements (GM) at 3 mo
      of 147 breastfed healthy term infants that were followed from birth. The quality
      of GM is a sensitive marker of neurological condition. The quality of GM was
      classified as normal-optimal, normal-suboptimal, mildly abnormal and definitely
      abnormal. Information on social and pre- and perinatal conditions and the
      duration of breastfeeding was collected prospectively. Logistical regression
      analyses were used to adjust for confounders. There was a positive association
      between breastfeeding duration and movement quality, with a saturation effect at
      the age of approximately 6 wk. In the group of infants breastfed for < or = 6 wk
      (n = 55), 18% exhibited normal-optimal GM, 47% normal-suboptimal GM, and 47%
      mildly abnormal GM. In contrast, in the group of infants breastfed for > 6 wk (n
      = 92), 43% exhibited normal-optimal GM, 45% normal-suboptimal GM, and 12% mildly
      abnormal GM. Exclusive breastfeeding for >6 wk was therefore associated with
      markedly less abnormal and more normal-optimal GM. Thus, we conclude that
      breastfeeding for > 6 wk might improve the neurological condition in infants.

PMID- 14652380
TI  - Common and country-specific dietary patterns in four European cohort studies.
AB  - The association between diet and cancer, predominantly investigated univariately,
      has often been inconsistent, possibly because of the large number of candidate
      risk factors and their high intercorrelations. Analysis of dietary patterns is
      expected to give more insight than analysis of single nutrients or foods. This
      study aimed to develop and apply a common methodological approach to determine
      dietary patterns in four cohort studies originating in Finland, the Netherlands,
      Sweden and Italy. Food items on each of the food frequency questionnaires were
      aggregated into 51 food groups, defined on the basis of their position in the
      diet pattern and possible relevance to cancer etiology. Exploratory factor
      analysis was used to analyze dietary patterns. Using a standardized approach, 3-5
      stable dietary patterns were identified, explaining 20-29% of total variance in
      consumption of the food groups. Two dietary patterns, which explained most of the
      variance, were consistent across the studies. The first pattern was characterized
      by high consumption of (salad) vegetables, the second by high consumption of
      pork, processed meat and potatoes. In addition, a few specifically national food
      patterns were identified. Sensitivity analyses showed that the identified
      patterns were robust for number of factors extracted, distribution of input
      variables and energy adjustment. Our findings suggest that some important eating
      patterns are shared by the four populations under study, whereas other eating
      patterns are population specific.

PMID- 14652381
TI  - A plant food-based diet modifies the serum beta-sitosterol concentration in
      hyperandrogenic postmenopausal women.
AB  - Plant sterols or phytosterols are common components of plant foods, especially
      plant oils, seeds and nuts, cereals and legumes. The most common phytosterols are
      campesterol, beta-sitosterol and stigmasterol. Phytosterols have anticarcinogenic
      properties. Previous studies have suggested that populations with low breast
      cancer incidence often consume diets high in phytosterols. The present study
      evaluated whether consumption of a plant food-based diet, low in animal fat, may
      increase serum phytosterol levels in postmenopausal women. One hundred and four
      women volunteers were randomized to dietary intervention or control groups. The
      dietary intervention included intensive dietary counseling to replace animal
      products with plant-based foods. Subjects in the dietary intervention group
      participated twice a week for 18 wk in workshops about the preparation and
      consumption of a plant food-based diet. The absolute change in serum total
      phytosterol concentration was greater in the dietary intervention group than in
      the control group. The percent change tended to differ between groups (P = 0.06).
      However, only for beta-sitosterol did the absolute and percent changes within a
      group differ significantly between groups (P = 0.0017). The decrease in serum
      total cholesterol in the dietary intervention group (-14%) was greater than that
      in the control group (-4%; P = 0.0005). The results of this study show that
      circulating levels of phytosterols can be affected by dietary modification. These
      findings indicate that phytosterols, in particular beta-sitosterol, can be used
      as biomarkers of exposure in observational studies or as compliance indicators in
      dietary intervention studies of cancer prevention.

PMID- 14652382
TI  - Redefining the glycemic index for dietary management of postprandial glycemia.
AB  - The glycemic index (GI) is a component-referenced index, defined as the effect on
      blood glucose of glycemic carbohydrate in a food as a percentage of the effect of
      an equal amount of glucose. GI is not suitable for dietary management of
      postprandial glycemia because it refers to glycemic carbohydrate, not to food, it
      is static, i.e., unresponsive to intake, and it is relative in that it can be
      used appropriately only for equicarbohydrate comparisons. Food values for dietary
      management, in contrast, must be food-based, intake responsive and sensitive to
      variations in composition typical of diets. The limitations of GI could be
      overcome by expanding its definition beyond glycemic carbohydrate, to foods. GI
      could then be used as a food-referenced index, expressed as glycemic glucose
      equivalents (GGE)/100 g food, and extrapolated to GGE per common standard measure
      (CSM) as a value for the glycemic load exerted by familiar food quantities.
      GI(food) and GGE/CSM would then be expressed as are nutrients in food composition
      databases, would lie on the same quantity-dependent continuum and could be used
      with nutrient information to provide a more complete nutritional profile of a
      food than is provided by nutrients alone. GI would then be a practical adjunct to
      food composition data, which was its intended role.

PMID- 14652384
TI  - Personal metabolomics as a next generation nutritional assessment.
AB  - Nutrition research is in the process of addressing a series of questions related
      to the future of diet and health. Are all humans the same with respect to their
      response to diet? If not, humans must be fed differently according to the
      differences in their genetics and metabolic needs. Are those differences self
      evident to the individual or their care-givers? If not, methods must be developed
      to measure the basis of differences between humans. Are the current sets of
      diagnostic biomarkers for disease appropriate and sufficient to distinguish the
      appropriate diets of humans for optimal metabolic health? If not, metabolites
      must be measured such that the differences in human metabolism are resolvable
      before they become diseased. Will a small subset of metabolic markers provide an
      indication of intended and unintended effects of diets that relate to overall
      metabolism? If not, comprehensive metabolic analyses (metabolomics) must be put
      in place to ensure that all aspects of health are accurately assessed.
      Inappropriate dietary choices are accelerating the development of chronic
      metabolic disease and threatening to overwhelm public health's ability to manage
      them. Nutrition and food sciences will need to collaborate with other scientific
      disciplines to develop and implement metabolic assessment technologies and to
      assemble annotated databases of metabolite profiles in humans, thus building the
      knowledge needed to link metabolism to diet and health. Biochemical and
      physiological research must be guided to define the mechanisms by which diet
      interacts with metabolism in different individuals. Integrating metabolism with
      the genetic and dietary variables that affect health is the role of nutrition
      sciences. Integrating personal nutritional value with food's other key values of
      safety, quality, comfort, delight, convenience and affordability is the role of
      food science. It is time for these two fields to address a common problem,
      metabolic health, with coordinated solutions.

PMID- 14652385
TI  - Nutrigenes, functional genomics and systems biology.
AB  - Traditionally, the classic reductionist approach attributes functions to
      individual genes. For instance, this has involved the analysis of motifs or the
      amino acid sequences of single gene products. It is unclear how the products of
      particular collections genes act together to provide higher order functionality
      in health and disease. To address this higher order problem, the function of
      collections of genes, as opposed to "one gene at a time" has to be studied.
      Accordingly, a model system is needed to test systems biology. In our studies, we
      used the homocysteine-folate metabolism as a model system.

PMID- 14652386
TI  - Phenotype- and gene-driven approaches to discovering the functions of mammalian
      genes.
AB  - All of us are involved in discovery science as we pursue the genes, networks,
      cellular processes and biophysical principles that govern our chosen biological
      question. For those of us who choose to proceed using plant or animal models to
      dissect the elements of our favorite biological system, there are many classical
      and newer approaches available for our use, including two complementary
      strategies by which the discovery process is proceeding at the Oak Ridge National
      Laboratory (ORNL). The ORNL has been known for six decades for its investigations
      of the effects of radiation and chemicals in inducing heritable mutations in
      mouse germ cells, and for using mouse mutations as tools for the cloning and
      characterization of mammalian genes. Our history and experience in making mouse
      models are being applied via these two complementary strategies: 1), a phenotype
      driven approach, in which mice carrying random chemically-induced mutations are
      screened for abnormal phenotypes; and 2) a gene-driven approach in which
      heritable single nucleotide polymorphisms (SNP) in preselected genes already
      thought likely to influence a biological system of choice can be recovered in
      live mice. The SNP-carrying mice can then be phenotyped for alterations in one's
      target biology. Both approaches have value and are necessary; while we can use
      mutations in genes that we already know to be of interest in our favorite biology
      to discover gene function, we also know that biology is full of surprise genes
      whose effects on our favorite biology would not be predicted and which will be
      identified only through phenotype screening.

PMID- 14652387
TI  - Modification of plant lipids for human health: development of functional land
      based omega-3 fatty acids.
AB  - We have remodeled canola seeds to accumulate the omega-3 fatty acid, stearidonic
      acid (SDA). In doing so, we have demonstrated the feasibility of developing a
      land-based source of functional omega-3 fatty acids on a large scale. Land-based
      omega-3 fatty acids represent a sustainable source of omega-3 fatty acids that
      can be produced on large acreages and delivered to consumers in a wide variety of
      functional foods. And unlike alpha-linolenic acid, SDA can provide
      eicosapentaenoic acid equivalence at moderate intakes. Widely applied, SDA
      enriched foods could become a valuable tool for delivering recommended levels of
      omega-3 fatty acids to large portions of the population. By obviating the need
      for dietary changes, SDA-enriched foods may facilitate increased compliance with
      recommendations for daily omega-3 intakes.

PMID- 14652388
TI  - Classification and an algorithmic approach to the reconstruction of femoral
      deficiency in revision total hip arthroplasty.

PMID- 14652389
TI  - Magnetic resonance imaging of the ankle: techniques and spectrum of disease.

PMID- 14652390
TI  - Percutaneous internal fixation of selected scaphoid nonunions with an
      arthroscopically assisted dorsal approach.
AB  - BACKGROUND: Preliminary reports have indicated that selected scaphoid nonunions
      i.e., those that are well aligned and without extensive sclerosis or bone
      resorption at the nonunion site-can be treated effectively with internal fixation
      alone. We examined the feasibility of percutaneous fixation in a series of such
      nonunions. METHODS: A consecutive series of fifteen patients with fibrous union
      or nonunion of a carpal scaphoid fracture with minimal sclerosis or resorption at
      the nonunion site were treated with rigid fixation alone (without bone graft)
      with a headless compression screw inserted with a dorsal percutaneous technique.
      RESULTS: Clinical examination, standard radiographs, and computed tomography
      scans confirmed union in all patients at an average of fourteen weeks. Nonunions
      treated less than six months after the injury healed faster than those treated
      later (p < 0.02). According to the Mayo modified wrist score, there were twelve
      excellent and three good results. CONCLUSIONS: The results in our series were due
      to careful examination and grading of the scaphoid nonunions preoperatively. The
      findings in this small series support the observation in earlier reports that
      percutaneous repair of selected scaphoid nonunions requires only rigid fixation
      to achieve healing.

PMID- 14652391
TI  - Minimal-incision total hip arthroplasty.

PMID- 14652392
TI  - Total hip arthroplasty through a minimally invasive anterior surgical approach.

PMID- 14652393
TI  - Rapid prototyping: the future of trauma surgery?

PMID- 14652395
TI  - Making sense of knee arthroplasty kinematics: news you can use.

PMID- 14652394
TI  - Polyethylene wear and acetabular component orientation.
AB  - BACKGROUND: Polyethylene wear contributes substantially to both periprosthetic
      osteolysis and aseptic loosening after total hip arthroplasty. Acetabular
      component orientation has been shown to affect the range of motion of the hip as
      well as contact stresses. A series of studies was designed to test the hypothesis
      that acetabular component orientation can affect the magnitude and direction of
      polyethylene wear. METHODS: A finite-element model was used to compute contact
      stresses during a normal gait cycle. Wear at the end of each gait cycle was
      calculated with use of the sliding-distance-coupled finite-element formulation.
      The wear that was calculated with use of finite-element analysis was validated by
      comparison with the findings of hip wear simulator studies with the acetabular
      liner oriented to simulate 45 degrees and 55 degrees of abduction. In a clinical
      study, fifty-six patients who underwent sixty hip arthroplasties with use of a
      single prosthetic design were followed for as long as five years. Radiographs
      were analyzed to measure the abduction angle of the acetabular component and
      polyethylene wear. RESULTS: The finite-element analysis predicted increased peak
      contact stresses with an increased abduction angle and reduced peak contact
      stresses with an increased anteversion angle. Linear wear rates ranging from
      0.036 to 0.045 mm/million cycles were also predicted, and increased acetabular
      abduction angles were predicted to be associated with higher linear wear rates.
      In the hip wear simulator studies, significantly different wear rates were found
      between the cups with acetabular abduction angles of 45 degrees and 55 degrees
      (mean, 17.2 compared with 21.7 mg/million cycles; p < 0.01). In the clinical
      study, radiographic analysis revealed significant correlation between the
      acetabular abduction angle and the linear polyethylene wear rate. A 40% increase
      in mean linear polyethylene wear was seen in cups with an abduction angle of
      >or=45 degrees. The direction of wear was more medial (by 9.4 degrees ) in cups
      with an abduction angle of <45 degrees. CONCLUSION: All three studies presented
      here underlined the importance of optimizing the position of the acetabular
      component. Careful attention to acetabular position may help to minimize wear.

PMID- 14652396
TI  - Current status of zirconia used in total hip implants.

PMID- 14652397
TI  - Impact of patellofemoral design on patellofemoral forces and polyethylene
      stresses.
AB  - BACKGROUND: The patellofemoral joint is a complex articulation because it relies
      mainly on soft-tissue constraints for stable tracking. The presence of a
      functioning posterior cruciate ligament and the design parameters of a total knee
      arthroplasty, such as trochlear groove alignment and cam-post configuration, can
      have a major effect on patellar biomechanics. METHODS: A finite element model of
      a knee implanted with femoral, tibial, and patellar components was generated. The
      model was validated by experimental testing of three cadaver knees implanted with
      a total knee prosthesis and a patellar force transducer. Two femoral component
      designs with different valgus angles of the trochlear groove (0 degrees and 7
      degrees ) were studied. The effects of femoral rollback, rotation of the femoral
      component, medialization of the patellar implant, and alignment of the trochlear
      groove on patellar forces were then analyzed. RESULTS: A consistent reduction of
      up to 7% in patellofemoral forces was seen with progressive magnitudes of femoral
      rollback. The 0 degrees -aligned trochlear groove generated some lateral
      patellofemoral shear force throughout knee flexion. The 7 degrees -aligned
      trochlear groove generated medial shear force at flexion angles of <20 degrees
      and lateral shear force at flexion angles of >20 degrees. A more medial patellar
      component position reduced peak lateral shear forces by up to 10 to 15 N.
      However, a corresponding increase in medial shear forces was seen. CONCLUSIONS:
      This model predicted substantial reduction in patellofemoral lateral shear forces
      with a medialized patellar component or with external rotation of the femur. The
      model supported the hypothesis that femoral rollback reduces patellofemoral
      forces by improving the efficiency of the extensor mechanism. CLINICAL RELEVANCE:
      Patellofemoral complications after total knee arthroplasty include anterior knee
      pain, patellar subluxation and dislocation, abnormal polyethylene wear and
      damage, and loosening. There is a wide variation in the design features of
      current total knee prostheses, such as the sagittal radius, depth, and
      orientation of the trochlear groove of the femur and the geometry of the patellar
      component surface. The finite element model used in the present study can provide
      insight into the effects of design parameters on patellofemoral forces and on
      local contact stresses.

PMID- 14652399
TI  - Three-dimensional morphology and kinematics of the distal part of the femur
      viewed in virtual reality. Part II.

PMID- 14652398
TI  - Use of a functional temporary prosthesis in a two-stage approach to infection at
      the site of a total hip arthroplasty.

PMID- 14652400
TI  - Reduced wear with oxidized zirconium femoral heads.

PMID- 14652401
TI  - Effects of walking gait on ultra-high molecular weight polyethylene damage in
      unicompartmental knee systems. A finite element study.

PMID- 14652402
TI  - Anthropometric measurements of the human knee: correlation to the sizing of
      current knee arthroplasty systems.
AB  - BACKGROUND: There is a paucity of data concerning the morphological dimensions of
      the distal part of the femur, the proximal part of the tibia, and the patella.
      The objective of this study was to analyze the exact anatomic data collected from
      a large group of patients undergoing total knee arthroplasty and to correlate the
      measurements to the dimensions of current prosthetic systems. METHODS: Eight
      different centers collected morphologic data from the distal part of the femur,
      the proximal part of the tibia, and the patella from 337 knees during total knee
      arthroplasty. Microcaliper measurements from templates and measuring guides were
      used to decrease intraobserver variation. The study included 188 women (209
      knees) and 107 men (128 knees) who had a mean age of sixty-nine years. A
      characterization of the aspect ratio (the medial-lateral to anterior-posterior
      dimensions) was made for the proximal aspect of the tibia and the distal part of
      the femur. Known dimensions from six prosthetic knee systems were compared with
      the morphologic data. RESULTS: A wide variation in the aspect ratio for the
      femoral component was seen among the six different prosthetic systems. For women,
      there was a significant association between the component size and the amount of
      medial-lateral overhang, with larger sizes having more overhang (p < 0.0001).
      Although the femoral aspect ratio for the morphologic data showed higher ratios
      for smaller knees and proportionally lower ratios for larger knees, the designs
      showed little change in the aspect ratio. The tibial aspect ratio from the
      morphologic data showed a higher ratio for smaller knees and a proportionally
      lower ratio for larger knees. The Duracon component tracked the decline in aspect
      ratio fairly well, whereas the other brands either did not change with anterior
      posterior dimension or actually increased (NexGen). Gender differences in the
      morphologic data were shown by the variable tibial aspect ratios. A comparison of
      the bone dimensions from the study data and the dimensions of the implants
      indicated that the smaller sizes were too small while the larger sizes tended to
      be too large. The average overall unresected patellar thickness was 23.7 mm.
      CONCLUSION: The results of this study will allow manufacturers to make more
      appropriate determinations of the sizes and aspect ratios of components for use
      in total knee arthroplasty.

PMID- 14652403
TI  - Calcaneotalotibial arthrodesis with a retrograde posterior-to-anterior locked
      nail as a salvage procedure for severe ankle pathology.

PMID- 14652404
TI  - Long-term bactericidal properties of a gentamicin-coated antimicrobial external
      fixation pin sleeve.

PMID- 14652405
TI  - Comparison of ligament-balancing techniques during total knee arthroplasty.

PMID- 14652406
TI  - Stabilization of proximal humeral fractures with an angular and sliding stable
      antegrade locking nail (Targon PH).

PMID- 14652407
TI  - Evaluation of a suture seat, a biodegradable suture fastener, to eliminate knot
      tying in arthroscopic rotator cuff repair.

PMID- 14652408
TI  - Does the total condylar 3 constrained knee prosthesis predispose to failure of
      revision total knee replacement?

PMID- 14652409
TI  - Pain in fungating wounds: another perspective.

PMID- 14652410
TI  - The health of home health care.

PMID- 14652411
TI  - Preparing the wound bed 2003: focus on infection and inflammation.
AB  - Wound bed preparation is the promotion of wound closure through diagnosis of the
      cause, attention to patient-centered concerns, and correction of systemic and
      local factors that may delay healing. To enhance the evidence base that may be
      lacking, a review of relevant literature was conducted and combined with input
      from the International Wound Bed Preparation Advisory Board and the Canadian
      Chronic Wound Advisory Board to create an updated examination of practices. A
      template based on expert opinion of the clinical actions corresponding to each
      step in the paradigm of preparing the wound bed is presented and the effects of
      local factors (tissue debridement, infection or inflammation, moisture balance,
      and edge effect [TIME]) are discussed. This review differentiates increased
      bacterial burden/infection in the superficial and deep wound bed compartments
      from inflammation and provides a topical approach to treatment. Inflammatory
      conditions causing leg ulcers, including pyoderma gangrenosum and vasculitis are
      reviewed. The topical combination of silver with absorptive dressings has led to
      new therapeutic options for increased bacterial burden in the surface wound
      compartment. A compilation of the available systematic reviews for the treatment
      of infection has been included as a background for the expert opinion.

PMID- 14652412
TI  - Parastomal hernias.

PMID- 14652413
TI  - A consensus report on the use of vacuum-assisted closure in chronic, difficult-to
      heal wounds.
AB  - Vacuum-assisted closure is an adjunctive therapy that utilizes negative pressure
      to remove fluid from open wounds through a sealed dressing and tubing which is
      connected to a collection container. Although introduced into practice for
      individuals with chronic wounds, evidence to support its use is limited. To
      compensate for the current gap between the evidence base and the need for best
      vacuum-assisted closure practices in the treatment of chronic wounds, the
      existing evidence base (case reports, case series, and studies) for pressure
      ulcers, diabetic foot ulcers, heel ulcers, and venous leg ulcers was retrieved
      and tabulated from relevant literature in PubMed and other sources. In addition,
      expert opinion was obtained through an 11-member Delphi panel of
      interdisciplinary wound care opinion leaders and educators. The panel included
      frequent (6) and less-frequent (5) vacuum-assisted closure users. The tabulated
      responses and the existing literature formed the basis of the best practice
      statements that serve to guide treatment approaches and stimulate further study.

PMID- 14652414
TI  - Searching for evidence-based medicine in wound care: an introduction.
AB  - During the last 10 years, wound care knowledge and treatment options, as well as
      the amount of information in the literature pertaining to wound and patient
      treatment options, have expanded rapidly. As a result, clinicians need to be able
      to review the existing literature with knowledge of the steps involved in
      evidence-based medicine. By identifying search strategies to improve information
      retrieval, time can be saved, new knowledge can be obtained, and with an
      understanding of clinical experience and patient-centered concerns, the best
      evidence for decision making can be utilized. The information retrieved can be
      categorized according to the level of evidence and clinical practice guidelines
      (documents in which an expert panel has reviewed the evidence and interpreted it
      for patient care) can be measured by the Appraisal of Guidelines for Research and
      Evaluation (AGREE) Instrument. Learning how to find and interpret the literature
      not only enhances clinical decision making, but it also may inspire additional
      inquiries that will add to the existing evidence base.

PMID- 14652415
TI  - Cost-effectiveness of becaplermin for nonhealing neuropathic diabetic foot
      ulcers.
AB  - Foot ulcers secondary to peripheral neuropathy and vascular disease are a
      commonly occurring complication for people with diabetes. Becaplermin, a
      genetically-engineered growth factor in a hydrogel vehicle, has been shown to be
      more effective than vehicle-only control in healing chronic foot ulcers of
      patients with adequate vasculature receiving best clinical care. To evaluate the
      cost-effectiveness of adding up to 20 weeks of becaplermin to a regimen of best
      clinical care, a 1-year decision-analytic model was developed and tested using
      data from a previously published controlled clinical study involving 251 people
      with diabetes (124 becaplermin/127 control) and adequate vasculature presenting
      with an infection-free ulcer that had failed to heal despite appropriate therapy.
      A 20-week healing rate was estimated based on the clinical trial data assuming
      becaplermin treatment was terminated at 10 weeks in non-responding ulcers, and
      follow-up data were extended to 1 year. Resource utilization was estimated by an
      expert panel using a modified Delphi approach. Using the model, it was found that
      incorporating becaplermin with best clinical care resulted in 26 fewer ulcer-days
      per patient per year compared to best clinical care alone with an incremental
      cost-effectiveness ratio of $6 per ulcer-day averted. Results were sensitive to
      becaplermin cost, efficacy, and effect on infection and recurrence rates. The
      clinical benefits of becaplermin deserve further investigation to enhance cost
      effectiveness information for informed treatment decisions.

PMID- 14652416
TI  - Managing oversight of colostomy irrigation in long term-care.

PMID- 14652417
TI  - Chronic wound pain and palliative cancer care.

PMID- 14652418
TI  - An interesting side effect of home oxygen therapy.

PMID- 14652419
TI  - Improving accuracy of wound measurement in clinical practice.
AB  - Wound measurement is an important component of wound assessment that has the
      potential to provide baseline measurements to predict treatment outcomes. This
      review critically evaluates the efficacy of current wound measurement techniques.
      Findings indicate that true area measurement and percentage of area reduction of
      wounds are useful parameters for differentiating between wounds that are/are not
      responding to treatment. Two stages of error have been found to result during
      tracing and calculation of wound surface area. Studies demonstrate that the
      greatest error occurs when identifying the wound margin, rather than when
      determining the area traced. The benefits of plotting wound healing rates include
      increased accuracy of healing prediction and early identification of factors
      delaying healing, which lead to rapid intervention, greater efficiency of
      treatment, and improved patient outcomes. A 20% to 40% reduction of wound area in
      2 and 4 weeks is likely to be a reliable predictive indicator of healing; the
      efficacy of this fact has been demonstrated specifically for venous leg ulcers.
      Specification of simple, clinical protocols could do much to improve accuracy of
      wound measurement. The literature indicates that future research should focus on
      development of a standardized method for measuring wounds and reporting wound
      healing rates.

PMID- 14652420
TI  - Long-term outcomes of full-thickness pressure ulcers: healing and mortality.
AB  - A non-experimental, retrospective analysis of pressure ulcer quality-assurance
      data was conducted from October 1997 to October 2002 to ascertain the
      relationship between the occurrence of nosocomial full-thickness pressure ulcers,
      healing, and mortality. The records of 74 patients (one woman, 73 men) who
      developed full-thickness pressure ulcers as inpatients at a regional Veterans
      Affairs medical center with acute, intensive, and long-term care units were
      assessed. Start day was the day that the ulcer was determined to have occurred
      and end day was the date the patient was pronounced dead. Major diagnoses for all
      patients, 70.7% for whom end-of-life planning was in effect, were cerebrovascular
      accident, diabetes, and cancer. The majority of ulcers were located in the
      sacral/coccygeal area (66.2%) and heel (16.2%). None of the ulcers healed in
      patients who died within 180 days of ulcer onset. A 180-day mortality rate of
      68.9% was noted in people who developed nosocomial full-thickness pressure
      ulcers, with an average of 47.0 days from ulcer onset to death. No deaths were
      related to the presence of the pressure ulcer. In this data set of people with a
      heavy disease burden who were approaching the end of life, the development of
      full-thickness pressure ulcers appeared to be a comorbid pathologic process.
      Collecting and analyzing long-term pressure ulcer healing and mortality outcomes
      is a missing component of pressure ulcer quality-assurance data.

PMID- 14652421
TI  - Hydrogel wound dressings: where do we stand in 2003?
AB  - Among the many categories of advanced wound dressing products available today,
      hydrogels are popular because they are effective, comfortable, easy to use, and
      cost effective. With proper use, these agents provide control of wound surface
      hydration, sometimes absorbing excess exudate and often providing moisture. This
      review describes the chemistry of hydrogels, the physiology of their interaction
      with the wound surface, and their role in patient care. Hydrogels have been
      proven effective in facilitating repair of pressure, diabetic, vascular, burn,
      and other wounds, and they have supplanted saline-moistened gauze for many
      applications. Clinical evidence suggests that no particular hydrogel is
      significantly more efficacious than any other, implying that other factors such
      as cost and ease of use may guide clinician choice of product within this class
      of wound dressings.

PMID- 14652423
TI  - Treatment of Class II, Division 2 malocclusion in adults: biomechanical
      considerations.

PMID- 14652424
TI  - 2003 JCO Orthodontic Practice Study, Part 2: Practice success.

PMID- 14652425
TI  - The simplified molar distalizer.

PMID- 14652426
TI  - Hot-water bath facilitates ceramic debracketing.

PMID- 14652427
TI  - Tablet PCs in orthodontics.

PMID- 14652428
TI  - Early lightwire treatment of bilateral impacted mandibular cuspids.

PMID- 14652429
TI  - Medical ethics in the neurosciences.
AB  - Doctors in India are heirs to a long tradition of ethics from their own forebears
      and from those from the West. This paper discusses ethical aspects of topics of
      relevance to neurological scientists such as brain death, neural transplant and
      whole brain transplant. Many other topics such as ethics in research, patients
      with AIDS, patients in a persistent vegetative state and euthanasia deserve
      similar consideration and debate.

PMID- 14652430
TI  - Neuronal stem cells.
AB  - Stem cells are self regenerating multipotential cells, found in the human brain
      which have the potential to differentiate into neurons, astrocytes and
      oligodendrocytes, and to self renew sufficiently to provide adequate number of
      cells in the brain. Neural stem cell grafts have been studied in a variety of
      animal models for various diseases like metabolic disorders, muscular
      dystrophies, neurodegenerative disorders, spinal cord repair, brain tumors and
      demyelinating disease. Stem cells may be derived from autologus, allogeneic or
      xenogenic sources. Histocompatibility is prerequisite for transplantation of
      allogeneic stem cells. Fetal tissue is the best current tissue source for human
      neural stem cells, however ethical issues are a major concern. Thus the prospect
      that stem cells could potentially be used to promote neurogenesis following
      injury and disease may seem attractive, yet the inherent problems associated with
      isolation and rejection in case of stem cells from another source, the potential
      to form tumors and ethical issues are the major challenges.

PMID- 14652431
TI  - Intraoperative MRI in neurosurgery: technical overkill or the future of brain
      surgery?
AB  - The development of image-guided neurosurgery represents a substantial improvement
      in the microsurgical treatment of tumors, vascular malformations and other
      intracranial lesions. Despite the wide applicability and many fascinating aspects
      of image-guided navigation systems, a major drawback of this technology is they
      use images, mainly MRI pictures, acquired preoperatively, on which the planning
      of the operative procedure as well as its intraoperative performance is based. As
      dynamic changes of the intracranial contents regularly occur during the surgical
      procedure, the surgeon is faced with a continuously changing intraoperative
      field. Only intraoperatively acquired images will provide the neurosurgeon with
      the information he needs to perform real intraoperative image-guided surgery. A
      number of tools have been developed in recent years, like intraoperative
      ultrasound and dedicated moveable intraoperative CT units. Because of its
      excellent imaging qualities, combined with the avoidance of ionizing radiation,
      MRI currently is and definitely will be in the future for the superior imaging
      method for intraoperative image guidance. In this short overview, the development
      as well as some of the current and possible future applications of MRI-guided
      neurosurgery is outlined.

PMID- 14652432
TI  - Intracranial pressure monitoring in a resource-constrained environment: a
      technical note.
AB  - Most published literature supports the use of ICP monitoring as a standard of
      care, though the benefit has never been conclusively proved by a prospective,
      randomized trial. Unfortunately, ICP monitoring is routinely performed in very
      few centers in India on a systematic basis. This is probably due to the common
      perception that it requires very sophisticated facilities and is prohibitively
      expensive for most patients. The author's institution was also faced with a
      comparable situation, and we have therefore developed a simple and economical
      system that is presented in practical detail. No custom-made equipment is
      necessary, and all disposables should be available in any hospital pharmacy. It
      is our hope that this will enable any center with an ICU for the management of
      neurosurgical patients to begin monitoring ICP. The system has been in consistent
      use for 3 years in our institution, and over 100 patients have been monitored
      successfully.

PMID- 14652433
TI  - Diagnostic validity of the Ki-67 labeling index using the MIB-1 monoclonal
      antibody in the grading of meningiomas.
AB  - BACKGROUND: About 10% of meningiomas behave aggressively and are graded atypical
      or malignant with important therapeutic and prognostic implications. Routine
      histological parameters are inconsistent in the assessment of their aggressive
      behavior. AIMS: The aim of this study was to find a threshold level of the MIB-1
      labeling index (MIB-1 LI) with the highest diagnostic validity in predicting
      histological atypia in a meningioma. SETTING AND DESIGN: This was a retrospective
      study of all atypical and malignant meningiomas diagnosed at our center between
      January 1995 and June 2000 and which were identified from the General Pathology
      Registry. MATERIAL AND METHODS: These meningiomas were assessed histologically
      with respect to the individual criteria of atypia. They were categorized
      according to the WHO 2000 classification as benign, atypical and anaplastic
      meningiomas, WHO Grades I, II and III respectively and by immunohistochemical
      analysis using the MIB-1 monoclonal antibody. STATISTICAL ANALYSIS: The
      diagnostically useful cut-off level for the prediction of atypia was estimated by
      calculating the sensitivity and specificity of the MIB-1 LI at various levels and
      a receiver operated characteristic (ROC) analysis was performed. The correlation
      between the individual histological parameters was studied and the MIB-1 LI was
      obtained using Fisher's exact test. RESULTS: Of the 40 meningiomas studied 21
      were benign, 16 atypical and 3 anaplastic. Atypical tumors had a higher MIB-1 LI
      than benign tumors, with diagnostic validity highest at a threshold of 7%, with a
      sensitivity of 0.86 and a specificity of 0.93, giving a likelihood ratio of 17.
      The MIB-1 LI correlated well with mitotic activity and the other individual
      criteria in the WHO 2000 definition of atypia in a meningioma. MIB-1 LI did not,
      however, correlate well with brain invasion. CONCLUSION: The MIB-1 LI has the
      highest validity in the diagnosis of atypia in meningiomas at a threshold level
      of 7%. The MIB-1 LI used in conjunction with histological features can help in
      making a recommendation regarding potentially aggressive behavior in meningiomas.

PMID- 14652434
TI  - Clinical signs as a guide for performing HSV-PCR in correct diagnosis of herpes
      simplex virus encephalitis.
AB  - BACKGROUND: Clinical criteria (symptoms) are not reliable enough to differentiate
      between different causes of encephalitis. The clinical presentation of herpes
      simplex virus encephalitis (HSVE) is not classically constant and in such a
      patient, therefore, it is vital to make early diagnosis. AIMS: To investigate
      satisfactory and crucial clinical signs as guide to perform HSV-PCR in a rapid
      diagnosis of herpes simplex virus encephalitis. MATERIAL AND METHODS: A total of
      156 CSF specimens from 70 patients with clinically suspected HSVE or
      meningoencephalitis were tested. The criteria for cases suspected of HSVE were
      fever >380C, altered mental status and other critical manifestations. CSF
      features, irregularity in brain CT scan and MRI findings were also assessed. All
      the specimens were collected before and after Acyclovir treatment. Polymerase
      chain reaction was performed using primers, which amplified DNA sequences for
      both HSV-1 and HSV-2. STATISTICAL ANALYSIS: To analyze data, two-tailed Fisher's
      exact test and the X2-test with Yates' correction were used as appropriate. The
      odds ratio was used to express the strength of association between the clinical
      factors and the PCR results. RESULTS: HSV-DNA was detected in 18% of the
      specimens, belonging to 25.7% of the patients. Results indicate that the majority
      of the clinical symptoms are not specific to definitive clinical diagnosis of
      HSVE, except alteration in the level of consciousness--odds ratio [0.27 (0.07
      0.96) (P=0.033)]; and lateralization sign--odds ratio [4.7 (0.98-22.6)
      (P=0.023)]. However, laboratory data, including total white blood cell count,
      especially the number of lymphocytes, and MRI findings could be suggested for HSV
      PCR examination. CONCLUSION: At the first admission, a preliminary finding of at
      least two important clinical features mentioned above along with the pattern of
      CSF cell and differential counts could be sufficient to perform HSV-PCR which
      could ultimately result in a rapid and correct diagnosis of herpes simplex
      encephalitis.

PMID- 14652436
TI  - Effect of mannitol in experimental spinal cord injury: an ultrastructural and
      electrophysiological study.
AB  - BACKGROUND: Although many experimental and clinical studies were performed on the
      pathophysiology and treatment of spinal cord injury (SCI), the
      electrophysiological and ultrastructural changes of the spinal cord were not
      precisely evaluated. AIMS: To investigate the effect of mannitol on Somatosensory
      Evoked Potentials (SSEP), postoperative neurological recovery and ultrastructural
      findings after an experimental SCI. SETTING: The experimental microsurgery
      laboratory of a university hospital. DESIGN: A prospective, randomized animal
      study. MATERIAL AND METHODS: Sprague-Dawley rats were used and divided into three
      groups (Groups I-III) for this study. Those in Group I were control animals who
      underwent laminectomy only, and non-traumatized spinal cord samples were obtained
      2 weeks later. SCI was produced in Groups II and III using clip compression
      technique, and cord samples were obtained 2 weeks later. The rats in Group II
      received 2 g/kg of 20% mannitol intraperitoneally, immediately and three hours
      after trauma was induced; and those in Group III received the same amount of 0,9%
      NaCl in the same manner. Preoperative and postoperative SSEP records at the end
      of 2 weeks were obtained. Electron microscopy examination of the cord samples was
      done at 2 weeks postoperatively. STATISTICAL ANALYSIS USED: Fischer's Exact Test.
      RESULTS: SSEP records, ultrastructural findings and clinical recovery showed that
      minor neural damage and significant recovery occurred in Group II. CONCLUSION:
      This study demonstrates that the administration of 2 g/kg of 20% mannitol
      produces significant improvement in the neural structures and protects the spinal
      cord following injury.

PMID- 14652435
TI  - Outcome prediction model for severe diffuse brain injuries: development and
      evaluation.
AB  - BACKGROUND: Intensive care resources for the management of severe diffuse brain
      injury patients (SDBI) are limited. Their optimal use is possible only if we can
      predict at admission which patients are unlikely to improve. AIMS: To develop a
      simple and effective model to predict poor outcome in patients with SDBI in order
      to help guide initial therapy. MATERIAL AND METHODS: The prognostic factors and
      outcomes of 289 patients with severe diffuse brain injury (GCS 3-8) were analyzed
      retrospectively. The prognostic factors analyzed were age, mode of injury, GCS at
      admission, pupillary reaction, horizontal oculocephalic reflex, and CT scan
      findings. Outcome at 1 month was classified as unfavorable--death or persistent
      vegetative state, or favorable--improvement with or without some disability. A
      stepwise linear logistic regression analysis was used to identify the most
      important predictors of poor outcome. A prediction model (NIMHANS model-NM) was
      developed using these factors. NM and several currently available outcome
      prediction models were prospectively applied in a separate group of 26 patients
      with severe diffuse brain injury managed with a different protocol. RESULTS: The
      most important predictors of poor outcome were found to be the horizontal
      oculocephalic reflex, motor score of GCS, and midline shift on CT scan. NM was
      found to be more sensitive (75%) and specific (67%) than most other models in
      predicting unfavorable outcome. NM had high false pessimistic results (33%).
      CONCLUSION: Prediction models cannot be used to guide initial therapy.

PMID- 14652437
TI  - Effect of losartan on albuminuria, peripheral and autonomic neuropathy in
      normotensive microalbuminuric type 2 diabetics.
AB  - BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are emerging as
      effective agents for preventing microvascular complications of diabetes. Losartan
      (angiotensin II antagonist) has an antihypertensive efficacy equivalent to ACE
      inhibitors, however its role in microvascular complications is not yet known.
      MATERIAL AND METHODS: We studied the efficacy of losartan (50 mg once daily for
      12 weeks) on albuminuria, peripheral and autonomic neuropathy in 25 normotensive
      microalbuminuric type 2 diabetics who were asymptomatic for neuropathy. RESULTS:
      Mean age was 46.6 +/- 4.34 years with the average duration of diabetes being 8.1
      +/- 1.54 years. Albuminuria improved significantly from 54 +/- 9.35 mg/L to 32.8
      +/- 25 mg/L (Paired student's t-test, P=0.0005) after therapy. Autonomic
      neuropathy was observed in 64% while 76% had peripheral neuropathy; but there was
      no improvement with losartan. The duration of diabetes had a negative correlation
      with autonomic neuropathy. It also had a similar negative correlation with median
      and common peroneal nerve motor conduction velocities (Pearson's correlation
      coefficient, r = -0.53, P<0.01 and r = -0.56, P<0.01 respectively) implying that
      autonomic and peripheral neuropathy worsen as a diabetic ages. However, no
      correlation existed between albuminuria and autonomic or peripheral nerve
      function. CONCLUSION: Autonomic and peripheral neuropathy are highly prevalent in
      normotensive microalbuminuric diabetic patients. Losartan remarkably improves
      albuminuria but a similar benefit in autonomic or peripheral neuropathy is not
      seen over 12 weeks. The future may see a defining role for losartan in
      microvascular complications in normotensive diabetics.

PMID- 14652438
TI  - A study of epilepsy-related psychosis.
AB  - The association of epilepsy and psychosis is studied. Among the 500 patients of
      epilepsy evaluated, there were 12 patients, 8 males and 4 females with epilepsy
      related psychosis. Their average age was 38 years. The interval between the age
      of onset of epilepsy and psychotic features was 9 years. Complex partial seizures
      were present in 7 patients and primary generalized tonic-clonic seizure was
      present in 1 patient. Four patients had post-ictal psychosis, 7 had acute
      interictal psychosis and 1 patient had chronic psychosis. The inter-ictal and
      chronic psychoses were schizophreniform whereas the post-ictal psychoses were
      not. EEG showed a temporal focus in 7 patients with complex partial seizures and
      an extra-temporal focus was identified in 4 out of the other 5 patients. Imaging
      (CT scan/MRI) revealed abnormalities in 10 patients. This study attempts to
      define the characteristics of psychoses occurring in epileptics.

PMID- 14652439
TI  - Evaluation of nimodipine in the treatment of severe diffuse head injury: a double
      blind placebo-controlled trial.
AB  - AIMS: The aim of this study was to establish whether nimodipine given orally soon
      after severe diffuse head injury for a period of three weeks improved outcome.
      MATERIAL AND METHODS: The present report analyzes the results of a prospective
      randomized double-blind placebo-controlled trial of nimodipine in 97 severe head
      injury patients (GCS Score < or =8) treated at the Department of Neurosurgery,
      NIMHANS, between January 1995 and June 1996. The patients were randomly assigned
      to two groups which were matched for age, sex, mode of injury, time interval from
      injury to admission, neurological status and CT scan findings. One group was
      given nimodipine 30 mg Q6H and the other group was given a placebo. The outcome
      of these patients at 6 months was evaluated using the Glasgow Outcome Score by
      and a psychologist. RESULTS: Results showed no significant difference in the
      functional and psychological outcome between the two groups, even in patients
      with subarachnoid hemorrhage. No adverse drug events were recorded. CONCLUSION:
      Oral nimodipine given for three weeks does not improve outcome in patients with
      severe diffuse head injury.

PMID- 14652440
TI  - Cryptococcal infection in patients with clinically diagnosed meningitis in a
      tertiary care center.
AB  - A retrospective analysis of 326 clinically diagnosed cases with meningitis over a
      period of five-and-a-half years was carried out to determine the prevalence of
      cryptococcal infection, its associated risk factors and therapeutic outcome.
      Fifty-four (16.6%) patients with cryptococcal meningitis were identified by smear
      examination, culture and/or cryptococcal antigen latex agglutination test.
      Records of 45 cryptococcal meningitis patients were available; 18 (40%) of them
      were apparently healthy immunocompetent individuals, 13 (28.9%) had human
      immunodeficiency virus (HIV) infection, 9 (20%) were renal transplant recipients,
      4 (8.9%) were diabetic and 1 (2.2%) had systemic lupus erythematosus. Ten (22.2%)
      patients died and 11 (24.4%) patients (all HIV-positive) left against medical
      advice. The present study indicates that cryptococcal infection is associated
      with high mortality. Presenting symptoms being indistinguishable from other
      causes of central nervous system infection, all patients with a clinical
      diagnosis of meningitis, irrespective of their immune status should be
      investigated for cryptococcal infection.

PMID- 14652441
TI  - Re-evaluation of reading frame-shift hypothesis in Duchenne and Becker muscular
      dystrophy.
AB  - The reading frame hypothesis has been proposed to explain the molecular basis of
      two allelic forms of muscular dystrophies, Duchenne/Becker muscular dystrophy
      (D/BMD). To evaluate the hypothesis in Indian D/BMD patients, we analyzed
      deletion of dystrophin exons in 147 DMD and 19 BMD patients. Our studies showed
      deviation of more than 30% from the reading frame hypothesis in DMD patients
      (47/147). The present results implicate a need to reevaluate the reading frame
      hypothesis.

PMID- 14652443
TI  - Hemangioblastoma: a study of radiopathologic correlation.
AB  - Computerized tomography (CT) scan and operative observations, and
      histolopathogical findings of 25 cases of intracranial hemangioblastoma were
      correlated. Solid hemangioblastomas showed a large number of thin-walled
      capillaries and abundant stromal cells with eosinophilic cytoplasm. Tumors with a
      cystic component and a mural nodule had a large number of stromal cells with
      vacuolated cytoplasm and microcysts.

PMID- 14652442
TI  - Venous air embolism: does the site of embolism influence the hemodynamic changes?
AB  - Three hundred and ninety-seven patients undergoing posterior cranial fossa
      surgery in the sitting position were prospectively studied to evaluate the
      incidence of venous air embolism (VAE) and its effects on hemodynamics. End-tidal
      carbon dioxide (ETC02) tension was monitored to diagnose VAE. A sudden and
      sustained decrease in ETC02 of more than 5 mmHg, in the absence of sudden
      hypovolemia, was presumed to be the result of VAE. The site of probable air
      entrainment (whether muscle, bone or tumor) was noted. Hemodynamic consequences
      were managed symptomatically. ETC02 monitoring detected VAE in 22% of the
      patients. The highest incidence of embolism resulted from muscles and tumor (40%
      in each case). Forty-two per cent of patients developed hypotension during the
      embolic episode (systolic BP less than 100 mmHg). Ten per cent of patients
      developed ventricular arrhythmias during the embolic episode. Air aspiration was
      successful in 4.8%. There were no statistically significant differences in the
      frequency of VAE among the different groups (P>0.05). Also, the frequency of
      hypotension and ventricular arrhythmias were not significantly different,
      irrespective of the source of VAE (P>0.05). The general condition of the patients
      in the preoperative stage had no influence on the incidence of embolism,
      hypotension or ventricular arrhythmias.

PMID- 14652444
TI  - Two cases of neuro-Behcet's disease mimicking cerebral tumor.
AB  - Two cases of neuro-Behcet's disease with isolated, solitary fronto-temporal and
      mesencephalic lesions respectively are reported. The cases were misdiagnosed as
      cerebral tumor. The postoperative outcome of the first patient was not
      satisfactory as he developed hemispheric edema. The second patient, with
      mesencephalic lesion, was treated only with corticosteroids, and the patient
      improved significantly. The lesion in this case resolved completely at six-month
      follow-up. We conclude that distinguishing the isolated solitary cerebral lesion
      of the Behcet's disease from a tumor may prevent surgical intervention.

PMID- 14652445
TI  - Choroid plexus papilloma of the posterior third ventricle during infancy &
      childhood: report of two cases with management morbidities.
AB  - We report two cases of posterior third ventricular choroid plexus papilloma, one
      in an 8-month-old infant and another in a two-year-old child. These cases
      presented with features of obstructive hydrocephalus. Both these patients
      underwent a ventriculo-peritoneal (VP) shunt surgery prior to the tumor excision.
      Following the VP shunt surgery both patients developed ascitis requiring
      exteriorization of the abdominal end of the shunt. There was a clear proof of CSF
      overproduction: 1400-1500 ml/day in the eight-month-old infant and 900-1200
      ml/day in the two-year-old child. In the former it was transient and could be
      treated with revision of the VP shunt whereas in the second case a ventriculo
      arterial shunt had to be done. In the second case a staged reduction cranioplasty
      was also performed for an enormously enlarged head (head circumference--74 cm).
      Interesting clinical and radiological findings and useful management strategies
      are described.

PMID- 14652446
TI  - Sporadic variety of pallido-pyramidal syndrome.
AB  - A rare case of a 40-year-old lady with a sporadic variety of the pallido
      pyramidal syndrome (PPS) is reported. She had marked parkinsonian features on the
      left side. Her single photon emission computed tomography showed left
      frontoparietal and basal ganglia hypoperfusion. CT scan and central motor
      conduction time were normal. She responded partially to a combination of
      trihexyphenydil and L dopa/C dopa therapy. In view of the diversity in the
      genetic, clinical and laboratory features, it is possible that PPS may be a
      heterogeneous condition.

PMID- 14652447
TI  - X-linked Charcot-Marie-Tooth disease with myokymia: report of a family.
AB  - The clinical and electrophysiologic profiles of two brothers suffering from
      Charcot-Marie-Tooth disease are presented. Both had widespread muscle twitching
      in the legs which showed electrophysiologic features of myokymia. Pedigree
      analysis suggested an x-linked recessive form of inheritance. This appears to be
      the first report of an Indian family with x-linked Charcot-Marie-Tooth disease.

PMID- 14652448
TI  - A patient with reversible pupil-sparing Weber's syndrome.
AB  - This is a case report of a lady who presented with pupil-sparing Weber's
      syndrome. She had left oculomotor nerve palsy with normal pupil and right
      hemiparesis. The patient subsequently made a good recovery. An ischemic lesion of
      the lower mid-brain was demonstrated on the MRI scan of the brain, which
      corresponds to the motor nucleus of the oculomotor nerve. The article also
      describes the neuroanatomy of the oculomotor nerve and how its partial lesions
      lead to sparing of the pupil. In addition, this case report documents that a
      pupil-sparing Weber's syndrome could be reversible.

PMID- 14652449
TI  - Delayed post-surgical development of dural arteriovenous fistula after cervical
      meningocele repair.
AB  - A 34-year-old female patient presented with an intracranial subarachnoid
      hemorrhage and was found to have a dural arteriovenous fistula at the site of
      previous cervical meningocele repair. Subsequent occlusion was achieved with
      endovascular embolization. To our knowledge, the phenomenon of the development of
      a spinal dural fistula at the site of a meningocele repair has not been recorded
      before.

PMID- 14652450
TI  - X-linked lissencephaly in an Indian family.
AB  - Neuronal migration disorders are an important differential diagnosis to be
      considered in the evaluation of intractable epilepsy. Though the underlying
      causative factors which govern their development are many and varied, genetic
      factors have been found to be contributory in a few forms of these disorders. An
      X-linked association with lissencephaly has recently been discovered and there
      are a few families described till now with this entity.

PMID- 14652451
TI  - Isolated fourth ventricular cysticercus cyst: MR imaging in 4 cases with short
      literature review.
AB  - We describe the magnetic resonance imaging (MRI) signal characteristics of
      isolated (solitary lesion) intra fourth ventricular cysticercus cyst in 4
      patients who clinically presented with obstructive hydrocephalus. All patients
      had routine MRI sequences (T1, T2, & proton density-weighted imaging), Fluid
      Attenuation Inversion Recovery (FLAIR), and post-gadolinium imaging followed by
      cerebrospinal fluid (CSF) flow study. It revealed a CSF signal intensity (on all
      pulse sequences), intra fourth ventricular cyst with a nidus (scolex), and wall
      enhancement. On T1-weighted and FLAIR images, the cyst wall and nidus (scolex)
      were seen in 3 cases, which were not seen in other routine sequences. The CSF
      flow study showed the intraluminal nature of the cyst. The MRI features suspected
      a cysticercus cyst, and per-operative findings and histopathological examination
      confirmed the diagnosis. The review of literature of the intra fourth ventricular
      cyst is briefly discussed.

PMID- 14652452
TI  - Hemiplegia: an initial manifestation of Japanese encephalitis.
AB  - A 7-year-old boy from an area endemic to Japanese encephalitis (JE) manifested
      with acute febrile illness, left hemiplegia and preserved consciousness during
      the prodromal phase of illness. The child developed features of encephalitis 48
      hours after the onset of hemiplegia. IgM MAC ELISA for JE virus revealed high
      titers in the serum and cerebrospinal fluid suggestive of JE. MRI of the brain
      showed asymmetrical bilateral thalamic hyperintense lesions on T2 weighted image,
      considered diagnostic of JE. Hemiplegia during the prodromal phase or as an
      initial symptom of JE is rather unusual.

PMID- 14652453
TI  - Herpes simplex encephalitis: some interesting presentations.
AB  - Herpes Simplex Encephalitis (HSE) is the most common cause of fatal viral
      encephalitis. A high index of suspicion is mandatory for early diagnosis and
      successful therapy to restrict morbidity and mortality. We report 4 patients of
      HSE, with interesting presentations, viz. brainstem involvement in an
      immunosuppressed patient, Kluver-Bucy Syndrome-a consequence of untreated HSE,
      HSE in the postpartum period mistaken as cortical venous thrombosis, and response
      to inadequate treatment. They demonstrate the wide spectrum of clinical features,
      pitfalls in diagnosis, and a variable response to therapy in HSE.

PMID- 14652454
TI  - Cerebrotendinous xanthomatosis: neuroimaging findings in two siblings from an
      Indian family.
AB  - Cerebrotendinous xanthomatosis (CTX) is exceptionally rare in the Indian
      population. We present and discuss the clinical, radiological and histopathologic
      findings in 2 siblings with CTX. Both the patients had juvenile cataract, mental
      retardation and marked cerebellar ataxia. The Achilles tendon swelling was
      present in only 1 patient (Case 2). MR imaging showed typical bilateral and
      symmetrical involvement of the dentate nuclei, inferior olives, brainstem and
      cerebellar hemispheric white matter. Although the diagnosis of CTX was made in
      the 3rd decade in both our cases, early diagnosis is possible if neuroimaging is
      done in the early course of the disease.

PMID- 14652455
TI  - Isolated ring-enhancing lesion of the brainstem in a patient with cyanotic heart
      disease: role of stereotactic intervention.
AB  - A 23-year-old man with cyanotic heart disease, presented with a ring-enhancing
      mass in the brainstem. Stereotactic intervention for this clinically and
      radiologically diagnosed pyogenic abscess, revealed a tuberculoma.
      Antituberculous therapy led to complete recovery. Stereotactic intervention is an
      ideal management strategy in patients with cyanotic heart disease and an isolated
      ring-enhancing mass in the brainstem.

PMID- 14652456
TI  - Suprasellar arachnoid cyst presenting with bobble-head doll movements: a report
      of 3 cases.
AB  - We report a series of three patients with suprasellar arachnoid cysts who
      presented with a rare 'bobble-head doll' syndrome. The abnormal head movements
      improved after surgical evacuation of the cysts in all the three cases. Various
      pathophysiological mechanisms involved in the bobble-head doll syndrome are
      discussed. The literature on suprasellar arachnoid cysts is briefly reviewed.

PMID- 14652457
TI  - Successful treatment of intrathecal morphine overdose.
AB  - A 47-year-old woman was diagnosed with secondary progressive multiple sclerosis,
      and was treated with intrathecal morphine for chronic pain via a slow-release
      subcutaneous pump. She accidentally received a 35-ml (510 mg) bolus injection of
      morphine by this route, which led to status epilepticus. She was treated with
      continuous intravenous naloxone infusion, and with medication to control
      hypertension and stop the seizure activity. The outcome was excellent, and the
      patient returned to her neurological baseline. This report describes the
      complications and the successful treatment of intrathecal morphine overdose. In
      order to prevent these serious errors, it is vital that only care providers who
      are proficient with these devices perform the refilling procedure.

PMID- 14652458
TI  - Unusual self-inflicted penetrating craniocerebral injury by a nail.
AB  - Penetrating injuries of the brain caused by a nail are rare. An interesting case
      of a patient with schizophrenia who attempted suicide by a self-inflicted
      penetrating intracranial injury using a nail is reported here. The literature
      related to this unusual case is reviewed.

PMID- 14652459
TI  - Juvenile amyotrophic lateral sclerosis with unusual presentation: a case report.
AB  - A case of juvenile amyotrophic lateral sclerosis with wasting confined to the
      distal part of one lower limb and the proximal part of the contralateral upper
      limb is being presented. A brief review of the literature is carried out.

PMID- 14652460
TI  - Functional recovery in ischemic stroke.
AB  - Functional outcome at three months was studied in 72 patients with ischemic
      stroke. The Canadian Neurological Scale was used to assess the severity of stroke
      at admission and functional outcome at 3 months was assessed using modified
      Rankin scale. The size and site of the infarct was noted from the initial CT.
      Risk factors like hypertension, diabetes, and serum cholesterol were analyzed.
      Initial neurological scoring at admission, and size and site of the infarct were
      significantly associated with functional recovery at 3 months.

PMID- 14652461
TI  - Temporal bone carcinoma with intradural extension.
AB  - A case of temporal bone carcinoma having intradural extension is reported. To the
      best of our knowledge, no such case has been reported so far.

PMID- 14652462
TI  - Merosin negative congenital muscular dystrophy: a short report.
AB  - We report a rare case of an infant with congenital muscular dystrophy who
      presented at birth with marked generalized hypotonia and normal mental
      development. Creatinine phosphokinase (CPK) level was markedly raised; however no
      white matter abnormalities were detected by brain imaging techniques.
      Immunohistochemical staining for merosin (laminin alpha 2) was negative, thereby
      confirming merosin-deficient congenital muscular dystrophy.

PMID- 14652463
TI  - Subdural hemorrhage associated with falcine meningioma.
AB  - A case of falcine meningioma associated with acute subdural hemorrhage is
      reported. The possible mechanisms of hemorrhage in the case are discussed. We
      believe that an early recognition and surgery can prevent neurological
      deterioration.

PMID- 14652464
TI  - Intravenous sodium valproate in status epilepticus.
AB  - A study was conducted to observe the effect of intravenous sodium valproate in
      status epilepticus. Eleven patients with status epilepticus, who were resistant
      to conventional drugs, underwent treatment with intravenous sodium valproate. The
      seizures were controlled in 10 patients within 24-48 hrs of starting treatment.
      No complications were observed during therapy. We conclude that intravenous
      sodium valproate can be recommended for Myoclonic status epilepticus and non
      convulsive status epileticus.

PMID- 14652465
TI  - Intracranial aneurysms causing spontaneous acute subdural hematoma.
AB  - Acute subdural hematoma is an uncommon presentation of the rupture of an
      intracranial aneurysm. We report two cases of intracranial aneurysms causing
      spontaneous acute subdural hematoma.

PMID- 14652466
TI  - Focal early onset of delayed radiation encephalopathy with brainstem signs.

PMID- 14652467
TI  - An early and isolated origin of the angular artery from the middle cerebral
      artery.

PMID- 14652468
TI  - Anticonvulsant-hypersensitivity syndrome in a child.

PMID- 14652469
TI  - Prognosis in children with head injury: inaccuracies in the analysis.

PMID- 14652470
TI  - Non-hypertensive intracerebral hemorrhage: some interesting observations.

PMID- 14652471
TI  - The effect of a fear-avoidance-based physical therapy intervention for patients
      with acute low back pain: results of a randomized clinical trial.
AB  - STUDY DESIGN: A randomized clinical trial with 4-week and 6-month follow-up
      periods. OBJECTIVE: To compare the effect of a fear-avoidance-based physical
      therapy intervention with standard care physical therapy for patients with acute
      low back pain. SUMMARY OF BACKGROUND DATA: The disability reduction strategy of
      secondary prevention involves providing specific treatment for patients that are
      likely to have chronic disability from low back pain. Previous studies have
      indicated that elevated fear-avoidance beliefs are a precursor to chronic
      disability from low back pain. However, the effectiveness of physical therapy
      intervention based on a fear-avoidance model is unknown. METHODS: Sixty-six
      consecutive patients referred to physical therapy with low back pain of less than
      8 weeks' duration were randomly assigned to receive fear-avoidance-based physical
      therapy (n = 34) or standard care physical therapy (n = 32). The intervention
      period lasted 4 weeks for this study. Disability, pain intensity, and fear
      avoidance beliefs measures were recorded before and after treatment. A 6-month
      follow-up of the same measures was obtained by mail. RESULTS: An intention-to
      treat principle (last value forward) was used for data analyses that tested the
      primary and secondary hypotheses. The prediction of disability at 4 weeks and 6
      months after treatment was significantly improved by considering the interaction
      between the type of treatment and the initial level of fear-avoidance beliefs.
      Both groups had significant within group improvements for disability and pain
      intensity. The fear-avoidance treatment group had a significant improvement in
      fear-avoidance beliefs, and fear-avoidance beliefs about physical activity were
      significantly lower than the standard care group at 4 weeks and 6 months after
      treatment. CONCLUSION: Patients with elevated fear-avoidance beliefs appeared to
      have less disability from fear-avoidance-based physical therapy when compared to
      those receiving standard care physical therapy. Patients with lower fear
      avoidance beliefs appeared to have more disability from fear-avoidance-based
      physical therapy, when compared to those receiving standard care physical
      therapy. In addition, physical therapy supplemented with fear-avoidance-based
      principles contributed to a positive shift in fear-avoidance beliefs.

PMID- 14652472
TI  - Importance of the back-cafe concept to rehabilitation after lumbar spinal fusion:
      a randomized clinical study with a 2-year follow-up.
AB  - STUDY DESIGN: A prospective, randomized, clinical study with a 2-year follow-up.
      OBJECTIVES: To analyze the effect of three different rehabilitation strategies
      for lumbar spinal fusion patients. SUMMARY OF BACKGROUND DATA: Fifteen percent to
      40% of lumbar spinal fusion patients are not expected to improve significantly
      over a 2-year period. Optimization of present forms of rehabilitation could
      possibly further improve the outcome. MATERIALS AND METHODS: Between 1996 and
      1999, 90 patients who had undergone lumbar spinal fusion were 3 months after
      surgery randomized to one of three different rehabilitation groups. Video group
      participants watched a video of exercises for training and were subsequently and
      only once provided instruction regarding their use. The back-cafe group was
      provided the same program as the video group, but as a supplement met with a back
      cafe with other fusion-operated patients three times over an 8-week period. The
      training group was provided physical therapy training twice weekly for 8 weeks.
      Functional outcome was evaluated at 6, 12, and 24 months after surgery by use of
      the low back pain rating scale and a questionnaire covering daily functions, work
      status, and a patient's contact with the primary sector. RESULTS: By 2-year
      follow-up, the back-cafe and video groups had less pain compared with the
      training group (P < 0.03). The back-cafe group was better at performing daily
      functions such as carrying bags of market items (P < 0.01), getting up from a
      chair (P < 0.01), and ascending staircases (P < 0.01) compared with the video and
      training groups. More in the back-cafe group resumed working after surgery
      compared with the two other groups (P < 0.04). The video group had significantly
      more contacts with general practitioners, physical therapists, and so on compared
      with the back-cafe and training groups (P < 0.001). CONCLUSION: The patients in
      the back-cafe group were significantly better at accomplishing a succession of
      daily tasks compared with the video and training groups 2 years after lumbar
      spinal fusion. At the 2-year follow-up the training group had a significant pain
      problem compared with the video and back-cafe groups. The video group had
      significantly more treatment demands outside the hospital system. This study
      demonstrates the relevance of the inclusion of coping schemes and questions the
      role of intensive exercises in a rehabilitation program for spinal fusion
      patients.

PMID- 14652473
TI  - ISSLS prize winner: The innervation of the intervertebral disc: a quantitative
      analysis.
AB  - OBJECTIVE: The first quantitative analysis of the innervation of the lumbar
      intervertebral disc is presented. METHODS: A sheep model was used allowing
      evaluation of the whole motion segment. Four sheep spines were used. One was
      processed for PGP 9.5 immunofluorescence and three were processed for PGP 9.5
      immunoperoxidase histochemistry. A count was made of the densities of innervation
      of the endplate and anulus, and these were compared. RESULTS: There is no
      significant difference between endplate and anulus innervation densities. The
      endplate innervation is concentrated centrally adjoining the nucleus. The richest
      area of innervation is in the perianular connective tissue. DISCUSSION: The
      lumbar intervertebral disc has a meager innervation. This is concentrated in the
      perianular connective tissue and the central endplate. Although receptor
      threshold is more closely related to nociceptive function than innervation
      density, these findings have important implications for any treatment of
      discogenic pain.

PMID- 14652474
TI  - ISSLS prize winner: Erythropoietin inhibits spinal neuronal apoptosis and pain
      following nerve root crush.
AB  - STUDY DESIGN: The authors investigated the association of L5 proximal nerve root
      injury with spinal cord neuronal apoptosis (histologic) and whether exogenous
      erythropoietin therapy might reduce apoptosis/or pain (behavioral). OBJECTIVES:
      The first objective was to determine whether nerve root crush induces specific
      programmed cell death of spinal neurons in the dorsal and ventral horn and
      whether this is correlated with pain behaviors. The second objective was to
      determine if exogenous erythropoietin might reduce apoptosis and/or pain. SUMMARY
      OF BACKGROUND DATA: Whether spinal neuronal apoptosis is correlated with pain
      behaviors following nerve root injury remains unknown. It has been hypothesized
      that neuroprotective factors may alleviate pain behaviors by protecting neurons
      from death. Erythropoietin is a hematopoietic growth factor that recently has
      been demonstrated as a potent neuroprotective factor against ischemic damage in
      the brain. The effects of erythropoietin on pain and spinal cord neurons have not
      been examined. METHODS: Sprague-Dawley rats received a L5 proximal nerve root
      crush injury or sham operation and were separated into two treatment groups for
      subcutaneous injection: 1) vehicle; 2) recombinant human erythropoietin, 2680
      U/kg. The rats were sacrificed, and spinal cords were removed for apoptotic and
      immunohistochemical analysis at 0, 1, and 3 days after surgery. To determine
      whether recombinant human erythropoietin prevented mechanical allodynia in
      animals with nerve root crushes (n = 12/group), both treatment groups were tested
      for pain behaviors using the von Frey test at -1, -2, -3, 1, 3, 7, 11, and 14
      days after surgery. RESULTS: After nerve root injury, apoptotic neurons increased
      by 80% in the ipsilateral spinal cord and moderately in contralateral spinal cord
      in vehicle-treated animals compared to uninjured controls. Recombinant human
      erythropoietin reduced (P < 0.05) neuronal apoptosis in both superficial dorsal
      and ventral horns of the spinal cord. This corresponded with identification of
      erythropoietin and its receptors on spinal neurons and reductions in TNF-alpha
      colocalization in ventral horn neurons. Mechanical allodynia developed in the
      corresponding ipsilateral hind paw within 1 day and was sustained until day 14.
      Recombinant human erythropoietin-treated animals demonstrated faster recovery
      from mechanical allodynia compared with vehicle-treated controls (P < 0.05).
      CONCLUSIONS: Our findings indicated that L5 proximal nerve root crush increased
      neuronal apoptosis in the superficial dorsal and ventral horn that correlated
      with mechanical allodynia. Exogenous recombinant human erythropoietin facilitated
      receptor-mediated neuroprotection of spinal cord neurons and faster recovery from
      mechanical allodynia. Erythropoietin may be a potential therapeutic factor for
      patients with low back pain by providing pain relief and neuroprotection.

PMID- 14652475
TI  - ISSLS prize winner: A novel approach to determine trunk muscle forces during
      flexion and extension: a comparison of data from an in vitro experiment and in
      vivo measurements.
AB  - STUDY DESIGN: Disc pressure and fixator load were measured in an in vitro setup
      and compared to in vivo measurements with the identical transducers from the two
      groups participating in this study. OBJECTIVES: The goal of this in vitro study
      was to determine the magnitude of trunk muscle forces during flexion and
      extension. The loading conditions in this study accounted for body weight, local
      and global muscles, and forces resulting from the support of the abdominal soft
      tissue in different postures. Resulting intersegmental motions and intradiscal
      pressure in each segment and the six load components in both rods of an internal
      fixator were determined. SUMMARY OF BACKGROUND DATA: The spine is primarily
      stabilized by muscle forces, which greatly influence spinal loads. However,
      little information exists on the magnitudes of trunk muscle forces during
      postures like flexion and extension of the upper body. METHODS: Seven human
      cadaveric lumbar spines were mounted in a spine tester and adjusted to different
      degrees of flexion and extension of the upper body with different hip flexions.
      For each specimen, a total of 124 load cases were studied. They included
      combinations of a vertical compressive load, a follower load and forces pulling
      with cables at a plate fixed at the cranial end of the specimen to simulate
      rectus abdominis, erector spinae, and a supporting force of the abdomen. The
      muscle forces were varied until the external moment, necessary to keep the lumbar
      spine specimen in the examined posture, was zero. This was achieved with
      different muscle force combinations. Loads on internal fixators as well as
      intradiscal pressure and intersegmental rotation at all levels were measured. The
      muscle force combination that caused intradiscal pressures and loads in the
      internal fixator closest to those measured in vivo were assumed to be the muscle
      forces which can be expected in vivo. RESULTS: Generally, intradiscal pressure
      was closer to in vivo measurements than the fixator loads. The force in the m.
      erector spinae increased with the flexion angle but was only slightly influenced
      by extension. The estimated forces in the erector spinae were 100 N for standing,
      130 N for 15 degrees extension, and 520 N for 30 degrees flexion of the upper
      body. Little influence was found on the intersegmental motion. CONCLUSION: In
      vitro loading conditions can be approximated closely to in vivo conditions with
      the simulation of an axial preload, local, and global muscles. This novel
      approach can help to estimate muscle forces, which can usually not be measured.
      The results from this study provide important input for FEM models, which may
      then allow the investigation of different load cases.

PMID- 14652476
TI  - Intervertebral stiffness of the spine is increased by evoked contraction of
      transversus abdominis and the diaphragm: in vivo porcine studies.
AB  - STUDY DESIGN: In vivo porcine study of intervertebral kinematics. OBJECTIVES:
      This study investigated the effect of transversus abdominis and diaphragm
      activity, and increased intra-abdominal pressure on intervertebral kinematics in
      porcine lumbar spines. BACKGROUND: Studies of trunk muscle recruitment in humans
      suggest that diaphragm and transversus abdominis activity, and the associated
      intra-abdominal pressure contribute to the control of intervertebral motion.
      However, this has not been tested in vivo. METHODS: Relative intervertebral
      motion of the L3 and L4 vertebrae and the stiffness at L4 were measured in
      response to displacements of the L4 vertebra imposed via a device fixed to the L4
      vertebral body. In separate trials, diaphragm and transversus abdominis activity
      was evoked by stimulation of the phrenic nerves and via electrodes threaded
      through the abdominal wall. RESULTS: When intra-abdominal pressure was increased
      by diaphragm or transversus abdominis stimulation, the relative intervertebral
      displacement of the L3 and L4 vertebrae was reduced and the stiffness of L4 was
      increased for caudal displacements. There was no change in either parameter for
      rostral displacements. In separate trials, the diaphragm crurae and the fascial
      attachments of transversus abdominis were cut, but intra-abdominal pressure was
      increased. In these trials, the reduction in intervertebral motion was similar to
      trials with intact attachments for caudal motion, but was increased for rostral
      trials. CONCLUSIONS: The results of these studies indicate that elevated intra
      abdominal pressure, and contraction of diaphragm and transversus abdominis
      provide a mechanical contribution to the control of spinal intervertebral
      stiffness. Furthermore, the effect is modified by the muscular attachments to the
      spine.

PMID- 14652477
TI  - Does intradiscal electrothermal therapy denervate and repair experimentally
      induced posterolateral annular tears in an animal model?
AB  - STUDY DESIGN: The effects of intradiscal electrothermal therapy (IDET) on
      intervertebral discs in sheep were studied experimentally. OBJECTIVES:
      Posterolateral annular lesions were experimentally induced and allowed to mature
      for 12 weeks in the intervertebral discs of sheep. IDET was performed in an
      attempt to denervate and repair the annular lesion. The histologic and
      immunohistochemical effects of IDET were studied. SUMMARY OF BACKGROUND DATA:
      IDET continues to be used as a minimally invasive treatment for chronic
      discogenic low back pain, with success rates reported in up to 70% of cases. The
      mechanism of action by which IDET exerts its effect is poorly understood.
      Proposed mechanisms include the contraction of collagen and the coagulation of
      annular nociceptors. An ovine model was used firstly to induce a posterolateral
      annular lesion, secondly to assess the innervation of such a lesion, and thirdly
      to assess the effect of IDET on this innervation. MATERIALS AND METHODS:
      Posterolateral annular incisions were made in 40 lumbar discs of 20 sheep. Twelve
      weeks were allowed for each annular lesion to mature. IDET was then performed in
      the disc with the posterolateral annular tear and in another control level. IDET
      was performed using a modified intradiscal catheter (Spine-CATH; Oratec
      Interventions, Menlo Park, CA). Temperatures were recorded in the nucleus (TN)
      and the posterior annulus (TPA). The spines were harvested at predetermined
      intervals up to 18 months. Histologic sections of the discs were graded for disc
      morphology to assess degeneration and immunohistochemical staining to assess
      potential denervation. RESULTS: Vascular granulation tissue consistent with a
      healing response was observed in the posterior annular tear of all incised discs
      from 12 weeks. Protein gene product 9.5 (PGP 9.5) positive nerve fibers were
      clearly identified in the adjacent periannular tissue and the outer few lamellae
      of the posterior annulus. During the IDET procedure, the mean maximum TPA was
      63.6C and the mean maximum TN was 67.C.At sacrifice, the number of nerve fibers
      identified in the posterior annular tear was the same for those specimens that
      had undergone IDET and those that had not. From 6 weeks after IDET, there was
      evidence of thermal necrosisin the inner annulus and adjacent nucleus but sparing
      the periphery of the disc. CONCLUSIONS: Vascular granulation tissue and posterior
      annular neo-innervation was observed in the experimentally induced posterolateral
      annular lesion. IDET delivered at 90C in the sheep consistently heated the
      posterior annulus and the nucleus to a temperature normally associated with
      coagulation of nociceptors and collagen contraction. IDET did not denervate the
      posterior annular lesion. Thermal necrosis was observed within the inner annulus
      and adjacent nucleus from 6 weeks after IDET. The reported benefits from IDET
      appear to be related to factors other than denervation and repair.

PMID- 14652478
TI  - Disc chondrocyte transplantation in a canine model: a treatment for degenerated
      or damaged intervertebral disc.
AB  - STUDY DESIGN: Disc degeneration and osteoarthritis are diseases of the matrix.
      Chondrocytes that have been removed from damaged cartilaginous tissues maintain a
      capacity to proliferate, produce, and secrete matrix components, and respond to
      physical stimuli such as dynamic loading. A dog model was used to investigate the
      hypothesis that autologous disc chondrocytes can be used to repair damaged
      intervertebral disc. OBJECTIVES: Given the capacity for the cells in vitro to
      produce matrix molecules that would be appropriate for disc chondrocytes, the
      focus of the experiment was to investigate whether the cells would continue to
      sustain metabolic function after transplantation. SUMMARY OF THE BACKGROUND DATA:
      No evidence for long-term integration exists for cell transplantation in species
      other than rats and rabbits. Furthermore, no controlled studies of 1-year
      duration have been published. MATERIALS AND METHODS: Disc chondrocytes were
      harvested and expanded in culture under controlled and defined conditions,
      returned to the same animals from which they had been sampled (autologous
      transplantation) via percutaneous delivery. The animals were analyzed at specific
      times after transplantation by several methods to examine whether disc
      chondrocytes integrated with the surrounding tissue, produced the appropriate
      intervertebral disc extracellular matrix, and might provide a formative solution
      to disc repair. RESULTS: In the context of degenerative changes in an injury
      model: (1) autologous disc chondrocytes were expanded in culture and returned to
      the disc by a minimally invasive procedure after 12 weeks; (2) disc chondrocytes
      remained viable after transplantation as shown by Bromodeoxyuridine incorporation
      and maintained a capacity for proliferation after transplantation as depicted by
      histology; (3) transplanted disc chondrocytes produced an extracellular matrix
      that displayed composition similar to normal intervertebral disc tissue. Positive
      evidence of proteoglycan content was supported by accepted histochemical staining
      techniques such as Safranin O-Fast Green; (4) both type II and type I collagens
      were demonstrated in the regenerated intervertebral disc matrix by
      immunohistochemistry after chondrocyte transplantation; and (5) when the disc
      heights were analyzed for variance according to treatment, a statistically
      significantcorrelation between transplanting cells and retention of disc height
      was achieved. CONCLUSIONS: Autologous chondrocyte transplantation is technically
      feasible and biologically relevant to repairing disc damage and retarding disc
      degeneration.

PMID- 14652479
TI  - Transmissibility of 15-hertz to 35-hertz vibrations to the human hip and lumbar
      spine: determining the physiologic feasibility of delivering low-level anabolic
      mechanical stimuli to skeletal regions at greatest risk of fracture because of
      osteoporosis.
AB  - STUDY DESIGN: Experiments were undertaken to determine the degree to which high
      frequency (15-35 Hz) ground-based, whole-body vibration are transmitted to the
      proximal femur and lumbar vertebrae of the standing human. OBJECTIVES: To
      establish if extremely low-level (<1 g, where 1 g = earth's gravitational field,
      or 9.8 ms-2) mechanical stimuli can be efficiently delivered to the axial
      skeleton of a human. SUMMARY OF BACKGROUND DATA: Vibration is most often
      considered an etiologic factor in low back pain as well as several other
      musculoskeletal and neurovestibular complications, but recent in vivo experiments
      in animals indicates that extremely low-level mechanical signals delivered to
      bone in the frequency range of 15 to 60 Hz can be strongly anabolic. If these
      mechanical signals can be effectively and noninvasively transmitted in the
      standing human to reach those sites of the skeleton at greatest risk of
      osteoporosis, such as the hip and lumbar spine, then vibration could be used as a
      unique, nonpharmacologic intervention to prevent or reverse bone loss. MATERIALS
      AND METHODS: Under sterile conditions and local anesthesia, transcutaneous pins
      were placed in the spinous process of L4 and the greater trochanter of the femur
      of six volunteers. Each subject stood on an oscillating platform and data were
      collected from accelerometers fixed to the pins while a vibration platform
      provided sinusoidal loading at discrete frequencies from 15 to 35 Hz, with
      accelerations ranging up to 1 g(peak-peak). RESULTS: With the subjects standing
      erect, transmissibility at the hip exceeded 100% for loading frequencies less
      than 20 Hz, indicating a resonance. However, at frequencies more than 25 Hz,
      transmissibility decreased to approximately 80% at the hip and spine. In relaxed
      stance, transmissibility decreased to 60%. With 20-degree knee flexion,
      transmissibility was reduced even further to approximately 30%. A phase-lag
      reached as high as 70 degrees in the hip and spine signals. CONCLUSIONS: These
      data indicate that extremely low-level, high-frequency mechanical accelerations
      are readily transmitted into the lower appendicular and axial skeleton of the
      standing individual. Considering the anabolic potential of exceedingly low-level
      mechanical signals in this frequency range, this study represents a key step in
      the development of a biomechanically based treatment for osteoporosis.

PMID- 14652480
TI  - Age distribution of three radiologic factors for lumbar instability: probable
      aging process of the instability with disc degeneration.
AB  - STUDY DESIGN: Cross-sectional study of 880 outpatients with low back and/or leg
      pain regarding age distribution of three radiologic factors. OBJECTIVES: To
      investigate the proportion and relationship of three individual radiologic
      factors with age on segmental instability in sagittal plane in consecutive age
      groups. SUMMARY OF BACKGROUND DATA: Previous studies revealed relationships
      between radiologic factors for instability and symptoms; however, little is known
      about the relationship between factors and age except in degenerative
      spondylolisthesis. METHODS: Excessive segmental motion, defined as more than 10
      degrees angulation, more than 3 mm translation, and more than 3 mm slip in
      neutral position, at the L4-L5 segment in 880 outpatients (389 men, 491 women)
      with low back and/or leg pain aged from 14 to 84 years was investigated by 3
      observers. The number and rate of the patients with each excessive motion were
      evaluated in continuous age groups of 5 years. RESULTS: The mean ages of patients
      with excessive angulation, translation, and slip in neutral position were 41.7,
      50.0, and 62.8 years, respectively. Both rates of excessive angulation and
      translation showed two peak patterns demonstrating peaks in the teens and 20s
      groups and in the over 46 age groups; however, angulation was predominant in
      younger age groups and translation was predominant in older age groups. Slip in
      neutral position was frequently observed in age groups over 46 and increased with
      age. CONCLUSIONS: The presence of patients with excessive angulation and
      translation in younger age groups suggests they have a hypermobile segment with
      least degenerated discs. Different predominant patterns of these radiologic
      factors may reveal the probable aging process of the instability.

PMID- 14652481
TI  - Outcome determinants of subacute low back pain.
AB  - STUDY DESIGN: Descriptive prognostic study. OBJECTIVES: To identify outcome
      determinants of subacute low back pain. SUMMARY OF BACKGROUND DATA: The factors
      predicting recovery from prolonged back pain among working adults are largely
      unknown. MATERIALS AND METHODS: One hundred sixty-four employed patients with
      subacute (duration of pain 4-12 weeks) daily low back pain were recruited from
      primary health care to a randomized study. Data on potential predictive factors
      were collected before randomization. In multiple regressions using repeated
      measures analysis, the treatment received was adjusted when determining the
      impact of the predictive factors. Dependent outcome variables used were pain,
      perceived functional disability, generic health-related quality of life,
      satisfaction with care, days on sick leave, use of health care, and costs of
      health care consumption measured, at 3-, 6-, and 12-month follow-ups. RESULTS:
      Age and intensity of pain at baseline predicted most of the outcomes. The
      perceived risk of not recovering was a stronger determinant of outcome than
      gender, education, or self-rated health status (which did not have any predictive
      value) or body mass index, expectations of treatment effect, satisfaction with
      work, or the presence of radicular symptoms below the knee (only slight
      predictive value). The only factors predicting the duration of sick leave were
      the duration of sick leave at baseline and the type of occupation. CONCLUSION:
      Age and intensity of pain are the strongest predictors of outcome. Accumulation
      of days on sick leave is predicted by the duration of sick leave at entry and the
      type of work, but not by pain, perceived disability, or satisfaction with work.

PMID- 14652482
TI  - Methods to locate center of gravity in scoliosis.
AB  - STUDY DESIGN: Prospective evaluation of the location of the center of gravity
      during supine, standing, and gait. OBJECTIVE: Develop methods to quantify center
      of gravity locations in patients with scoliosis and controls and to evaluate the
      merit of the quantitative assumptions relative to spinal fusion surgery. SUMMARY
      AND BACKGROUND DATA: The center of gravity, or balance point of the body, is
      generally considered to be the single best estimate of the body's location. To
      date, investigators have not examined the body's center of gravity location to
      assist surgical planning to maintain and/or restore coronal and sagittal plane
      balance, nor have they used center of gravity location to help assess surgical
      outcomes. MATERIALS AND METHODS: The whole-body center of gravity (MR-COG) was
      determined for three subjects from magnetic resonance imaging data obtained
      supine. The whole-body center of gravity was also determined using subject
      specific (SS-COG) and literature-based (STD-COG) segment center of gravity
      locations in conjunction with a video motion capture system obtained supine,
      standing and during gait. RESULTS: Differences existed among the three methods of
      determining COG locations in supine, with the SS-COG and MR-COG being most
      closely aligned. Results from gait data indicated typical anterior/superior and
      right/left COG shifts during the gait cycle. The SS-COG method consistently
      determined a COG location inferior to the STD-COG method; however, variation
      within the gait cycle was similar. Shifts in COG locations relative to a
      coordinate system fixed in the pelvis were more than 5 cm in the
      superior/inferior direction, approximately 4 cm in the anterior/posterior
      direction, and minimal in the left/right direction. CONCLUSIONS: Methods have
      been developed to determine locations of the whole body COG in both preoperative
      and postoperative subjects undergoing spinal fusion surgery and controls. The
      methods are robust to include men and women, subjects with and without
      instrumentation, and subjects in various positions including gait.

PMID- 14652483
TI  - Peculiar fracture of the cervical spine: a rara avis.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report a peculiar case of the cervical
      spine that ensued after a sudden harsh extension along with its prompt evaluation
      and management. SUMMARY OF BACKGROUND DATA: Fractures of the cervical spine do
      occur and are usually inconsequential because of the rarity of accompanying
      neurologic complications. Accordingly, they are often treated conventionally.
      MATERIALS AND METHODS: Cervical radiographies and magnetic resonance imaging were
      performed to depict the fracture. RESULTS: Cervical radiographies demonstrated
      the C7 fracture in our patient but the magnetic resonance imaging also disclosed
      a T1 fracture. He was treated by physical therapy and close follow-up.
      CONCLUSIONS: This type of an unexpected incident in daily life can be seen and it
      should always orient the clinicians toward being vigilant against concomitant
      vertebral fractures or neurologic complications. And once it is proven that the
      spinal cord is not compromised, one might feel comfortable in treating solely
      these inconsequential fractures conventionally.

PMID- 14652484
TI  - Intraspinal synovial cyst communicating with the C1-C2 facet joints and
      subarachnoid space associated with rheumatoid atlantoaxial instability.
AB  - STUDY DESIGN: The first case of intraspinal synovial cyst communicating with the
      C1-C2 facet joints and subarachnoid space associated with rheumatoid atlantoaxial
      instability is presented. OBJECTIVES: To describe the diagnosis and successful
      treatment of a synovial cyst of the C1-C2 junction in a patient with rheumatoid
      arthritis and atlantoaxial instability. SUMMARY OF BACKGROUND DATA: Intraspinal
      synovial cysts of the C1-C2 junction are extremely rare. Neither association with
      rheumatoid atlantoaxial instability nor communication with the C1-C2 facet joints
      and the subarachnoid space has been previously reported in a synovial cyst of the
      C1-C2 junction. MATERIALS AND METHODS: The clinical and radiologic features of a
      71-year-old woman with a symptomatic synovial cyst of the C1-C2 junction with
      rheumatoid atlantoaxial instability are detailed. Posterior atlantoaxial fusion
      alone was performed. RESULTS: Preoperative magnetic resonance images demonstrated
      a large cystic mass around the dens, compressing the spinal cord. The mass was of
      low signal intensity on T1-weighted images, was of high signal intensity on T2
      weighted images, and was enhanced marginally with gadolinium-DTPA on T1-weighted
      images. Computed tomograms performed after myelography disclosed the cyst around
      the dens communicating with the subarachnoid space and the C1-C2 facet joints.
      Spontaneous regression of the cyst was identified on the magnetic resonance
      images 3 months after surgery. One year after surgery, myelopathic symptoms were
      improved. CONCLUSION: An intraspinal cyst communicating with the C1-C2 facet
      joints and subarachnoid space associated with rheumatoid atlantoaxial instability
      was reported. Computed tomograms after myelography were useful in delineating the
      relationships among the synovial cyst, facet joints, and the subarachnoid space.
      Spontaneous regression of the cyst and clinical improvement were achieved by C1
      C2 posterior fusion alone.

PMID- 14652485
TI  - Visualization of spinal injection procedures using gadolinium contrast.
AB  - STUDY DESIGN: A series of six case reports. OBJECTIVE: The case reports
      demonstrate successful use of gadolinium contrast for visualization of spinal
      injection procedures. SUMMARY OF BACKGROUND DATA: A variety of spinal injection
      procedures were performed with gadolinium contrast. Adequate visualization was
      accomplished with gadolinium in performing these injections and demonstrated that
      it is a viable alternative to nonionic iodinated contrast materials. MATERIALS
      AND METHODS: The case reports included a chart review, performance of spinal
      injections with gadolinium under fluoroscopic guidance, and postprocedure follow
      up at 2 and 12 weeks. RESULTS: Gadolinium was visible under fluoroscopy in all
      six cases, demonstrating its value in performing spinal injection procedures as
      an alternative to nonionic iodinated contrast materials. CONCLUSION: Gadolinium
      is a viable alternative to nonionic iodinated contrast materials for
      visualization of spinal injection procedures.

PMID- 14652486
TI  - Multiple tuberculomas in the brain and spinal cord: a case report.
AB  - STUDY DESIGN: A case of disseminated tuberculoma in the spinal cord and brain is
      reported. OBJECTIVES: To present a case of disseminated tuberculoma in the spinal
      cord and brain and to describe the unusual pathologic features and clinical
      presentation. SUMMARY AND BACKGROUND: DATA Intramedullary tuberculoma concomitant
      with intracerebral disseminated tuberculoma is rare. Only one other case has been
      reported in the world literature. This represents the second reported case of
      this unusual lesion. MATERIALS AND METHODS: The authors report a 67-year-old man
      with miliary tuberculosis of the lung and started on antituberculous therapy. His
      pulmonary complaints were resolved, but he presented acute paraparesis caused by
      tuberculomas in the thoracolumbar spinal cord. MRI showed more tuberculomas in
      the brain stem, cerebellum, and cerebral hemispheres. RESULTS: After 6 months,
      the patient's muscle power gradually improved with a combination of medical and
      surgical management. CONCLUSIONS: Our experience indicates that antituberculous
      medication is effective in managing multiple central nervous system tuberculomas.
      The purpose of surgical intervention is to decompress the cord or brain when
      progressing neurologic defects occur and to examine the tissue pathologically.

PMID- 14652487
TI  - Environmental physiology in MSSE.

PMID- 14652488
TI  - Shoulder pain: a comparison of wheelchair athletes and nonathletic wheelchair
      users.
AB  - PURPOSE: The purpose of this study was to directly compare the onset and
      prevalence of shoulder pain in athletic and nonathletic wheelchair users.
      METHODS: A questionnaire was distributed to athletic and nonathletic wheelchair
      dependent populations. This inquired about presence and duration of shoulder
      pain, age of subject, level of injury, duration of time since injury, wheelchair
      use, involvement in sports, and training habits. A total of 257 subjects were
      involved in the study. RESULTS: The odds of having shoulder pain were twice as
      high among nonathletes as they were among athletes. This finding represents a
      significant difference over and above age differences, differences in years spent
      in a wheelchair, and differences in level of spinal cord injury. Athletes also
      have an average of 12 yr free of shoulder pain after becoming wheelchair bound,
      whereas nonathletes have only 8 yr. CONCLUSION: Promotion of active exercise for
      wheelchair users is encouraged to decrease shoulder pain, resulting in more
      functional, pain-free years.

PMID- 14652489
TI  - Effects of tai chi on joint proprioception and stability limits in elderly
      subjects.
AB  - PURPOSE: The objectives of this study were to examine whether elderly Tai Chi
      practitioners have developed better knee joint proprioception and standing
      balance control than control subjects. METHODS: Tai Chi and control subjects (N =
      21 each, aged 69.4 +/- SD 5.5 and 72.3 +/- 6.1 yr, respectively) were matched
      with respect to age, sex, and physical activity level. Passive knee joint
      repositioning was used to test joint proprioceptive acuity. Control of body sway
      during static standing and subjects' intentional weight shifting to eight
      different spatial limits of stability within their base of support were conducted
      using force platform measurements. RESULT: Tai Chi practitioners were found to
      have better knee joint proprioceptive acuity, in that they made less absolute
      angle error (2.1 +/- 1.2 degrees ) than control subjects (4.0 +/- 3.4 degrees,
      with P = 0.023) in passive knee joint repositioning. No significant difference
      was found in the anteroposterior and mediolateral body sway during static
      standing (P > 0.05). However, Tai Chi practitioners initiated voluntary weight
      shifting in the limits of stability test more quickly (reaction time: 0.8 +/- 0.2
      s for Tai Chi practitioners) than control subjects (1.1 +/- 0.3 s; P = 0.008).
      Moreover, they could lean further without losing stability (maximum excursion:
      5.2 +/- 0.6% for Tai Chi practitioners and 4.6 +/- 0.5% for control subjects; P =
      0.001) and showed better control of their leaning trajectory (directional
      control: 75.9 +/- 10.0% for Tai Chi practitioners and 68.5 +/- 6.9% for control
      subjects; P = 0.008). CONCLUSIONS: These results demonstrate that long-term Tai
      Chi practitioners had improved knee joint proprioception and expanded their
      limits of stability during weight shifting in stance.

PMID- 14652490
TI  - The effect of Tai Chi Chuan on the autonomic nervous modulation in older persons.
AB  - PURPOSE: This study evaluated the effect of Tai Chi Chuan (TCC) on the autonomic
      nervous modulation in older persons. METHODS: Twenty TCC practitioners and 20
      normal controls were included in this study. The stationary state spectral heart
      rate variability (HRV) measures between TCC practitioners and normal controls,
      and the sequential changes in HRV measures after classical Yang's TCC were
      compared. RESULTS: The total power, very low-frequency power, low-frequency
      power, normalized low-frequency power, and low-/high-frequency power ratios in
      TCC practitioners were all significantly higher than those of normal controls,
      whereas the heart rate and systolic and diastolic blood pressures were not
      different between these two groups of subjects. After TCC, the normalized high
      frequency power increased significantly from 22.8 +/- 14.6 normalized units (nu)
      before TCC to 28.2 +/- 16.1 nu 30 min after TCC and to 30.6 +/- 18.4 nu 60 min
      after TCC. In contrast, the low-/high-frequency power ratio decreased
      significantly from 2.5 +/- 2.4 before TCC to 1.8 +/- 1.4 30 min after TCC and to
      2.2 +/- 2.9 60 min after TCC. The heart rate, systolic blood pressure, diastolic
      blood pressure, mean arterial blood pressure, and pulse pressure also decreased
      sequentially after TCC. CONCLUSION: The short-term effect of TCC was to enhance
      the vagal modulation and tilt the sympathovagal balance toward deceased
      sympathetic modulation in older persons. TCC might be good health-promoting
      calisthenics for older persons.

PMID- 14652491
TI  - Time course of arterial vascular adaptations to inactivity and paralyses in
      humans.
AB  - PURPOSE: The aim of the present study was to assess the time course of vascular
      adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI)
      population offers a unique "human model of nature" to assess peripheral vascular
      adaptations and its time course to extreme inactivity and paralyses. METHODS:
      Arterial diameters and red blood cell velocity of the carotid artery (CA), common
      femoral artery (FA), and brachial artery (BA) were measured using echo Doppler
      ultrasound. Fifteen SCI persons with lesions varying from 6 wk to 13 months
      postinjury participated in a cross-sectional study (SCI-CS), 6 SCI individuals
      were included for longitudinal measurements (SCI-L) at weeks 6, 8, 12, 16, 20,
      and 24 after the trauma, and 16 able-bodied individuals served as a control group
      (C). RESULTS: Within 6 wk after the SCI, diameter (SCI-CS: 0.68 +/- 0.09 cm, SCI
      L: 0.67 +/- 0.04 cm, C: 0.95 +/- 0.07 cm) and blood flow (SCI-CS: 299 +/- 112 mL
      x min(-1), SCI-L 279: +/- 52 mL x min(-1), C: 405 +/- 97 mL x min(-1)) of the
      femoral artery were significantly reduced (P < 0.001), and local femoral wall
      shear rate was almost doubled in SCI-CS and SC-L compared with C (P < 0.001). No
      further changes in femoral arterial properties were observed between week 6 and
      13 months postinjury in SCI-L as well as SCI-CS. Carotid and brachial artery
      diameter and flow were similar in SCI and C and did not change between 6 wk and
      13 months after the injury. CONCLUSION: We conclude that the process of vascular
      adaptations to inactivity and paralyses in humans seems to be largely completed
      within weeks.

PMID- 14652492
TI  - ACE I/D polymorphism and cardiac adaptations in adolescent athletes.
AB  - PURPOSE: The aim of this cross-sectional study was to determine whether there is
      a correlation between left ventricular hypertrophy (LVH) and angiotensin
      converting enzyme (ACE) insertion/deletion (I/D) polymorphism in adolescent
      athletes. METHODS: Seventy-five competitive soccer players (aged 15 +/- 1.2 yr)
      and 52 untrained control subjects (aged 15 +/- 1.6 yr) were examined with
      echocardiography (echo) and bioelectrical impedance analysis. The ACE genotype of
      all subjects was determined by PCR and correlated with left ventricular mass
      (LVM) indices. RESULTS: Allele frequencies were comparable between athletes and
      controls. Body surface area (BSA), fat-free mass (FFM), and all mean echo
      measurements were significantly greater in athletes than in controls. LVM and LVM
      indices for both BSA and FFM were all significantly greater in athletes than in
      controls (LVM 195.3 +/- 32 g vs 165.3 +/- 37.6 g; LVM/BSA 115.5 +/- 18.9 g x mq(
      1) vs 95 +/- 18.2 g x mq(-1); LVM/FFM 3.5 +/- 0.5 vs 3 +/- 0.54, P < 0.001 for
      the three variables). Left ventricular hypertrophy was found in 17 (23%)
      athletes. There was no correlation between ACE I/D polymorphism and athletes with
      LVH as the II and DD genotype frequencies were identical (41%). However, in
      athletes with LVH, the presence of the D allele was associated with a greater LVM
      index than compared to homozygous II genotype (LVM = 145 +/- 7.6 g x mq(-1) in
      DD+ID group vs 135 +/- 2.9 g x mq(-1) in II group, P = 0.008). CONCLUSIONS: The
      results of the study show that significant changes occur in cardiac morphology
      and function in adolescent athletes. Interestingly, the ACE I/D polymorphism was
      associated with the degree of cardiac hypertrophy but not with the occurrence of
      LVH itself.

PMID- 14652493
TI  - eNOS T-786C genotype, physical activity, and peak forearm blood flow in females.
AB  - BACKGROUND: The purpose of the present study was to determine interactive and
      main effects of the eNOS T-786C gene polymorphism and habitual physical activity
      level on forearm vascular resistance (FVR) and forearm blood flow (FBF) at rest
      and during 3 min of reactive hyperemia. METHODS: We studied healthy, Caucasian
      (age 25 +/- 1 yr), sedentary (maximal oxygen consumption, [OV0312]O2max: 33.8 +/-
      1 mL x kg(-1)x min(-1)), and endurance-trained ([OV0312]O2max: 45.3 +/- 1 mL x
      kg(-1)x min(-1)) women. FBF was measured using venous occlusion plethysmography
      before (resting) and after 5 min of arm arterial occlusion at 1 (peak
      vasodilation), 2, and 3 min of reactive hyperemia. [OV0312]O2max was measured
      using a standard treadmill protocol, and skinfolds were measured to estimate body
      composition. RESULTS: There was a significant interaction between eNOS genotype
      and physical activity level on resting FVR (P = 0.0003). Sedentary subjects with
      the TT genotype had the lowest resting FVR, but among the endurance-trained
      group, the TC+CC genotype group had the lowest resting FVR. This interaction was
      reflected in the resting FBF values (P = 0.03). After accounting for important
      covariates, there was a main effect of eNOS genotype on peak FBF (TT, 7.0 +/- 0.3
      vs TC+CC, 5.9 +/- 0.4 mL x 100 mL(-1) FAV x min(-1), P = 0.03) and the percent
      decrease in FVR (TT, -62 +/- 2 vs TC+CC, -51 +/- 4%, P = 0.04) at minute 1.
      CONCLUSIONS: These results of the interactive effects suggest that young females
      possessing a C allele may reduce their resting FVR by improving their
      cardiovascular fitness level, but TT homozygotes, who may have normal eNOS gene
      function, may not improve their resting FVR with improvements in cardiovascular
      fitness. Furthermore, regardless of physical activity level, the TT genotype
      showed a favorable hemodynamic response during reactive hyperemia compared with
      the C allele carriers.

PMID- 14652494
TI  - PGC-1alpha genotype modifies the association of volitional energy expenditure
      with [OV0312]O2max.
AB  - Sedentary lifestyles are increasingly common and result in low cardiorespiratory
      fitness ([OV0312]O2max), a well-established predictor of early mortality and
      coronary heart disease (CHD). Adaptation in [OV0312]O2max after exercise training
      varies considerably between people. Because there are hereditary components to
      fitness, it is likely that genetic factors explain some of this variability.
      PPARGC1 (PGC-1alpha) coactivates genes involved in energy transduction and
      mitochondrial biogenesis. Transgenic mouse data demonstrate that overexpression
      of PGC-1alpha mRNA increases endurance capacity by transformation of nonoxidative
      to oxidative skeletal muscle tissue. Other murine studies demonstrate that
      exercise increases PGC-1alpha mRNA expression. PURPOSE: To explore whether a
      candidate polymorphism in the PGC-1alpha gene modifies the association between
      physical activity energy expenditure (PAEE) and predicted [OV0312]O2max
      ([OV0312]O2max.pred). METHOD: We examined whether the Gly482Ser polymorphism of
      PGC-1alpha modified the relationship between objectively measured PAEE and
      [OV0312]O2max.pred in a population-based sample of 599 healthy middle-aged
      people. PAEE was assessed using individual calibration with 4 d of heart rate
      monitoring. [OV0312]O2max.pred was measured during a submaximal exercise stress
      test on a bicycle ergometer. RESULTS: Homozygosity at the Ser482 allele was found
      in 12.7% of the cohort, whereas 38.9% and 48.4% carried the Gly482Gly and
      Gly482Ser genotypes, respectively. The association between PAEE and
      [OV0312]O2max.pred (mL x kg(-1) x min(-1)) was strongest in people homozygous for
      the Ser482 allele (beta = 12.03; P < 0.00001) compared with carriers of the Gly
      allele (beta = 5.61; P < 0.00001). In a recessive model for the Ser482 allele,
      the interaction between PAEE and genotype on [OV0312]O2max.pred (L x min(-1)) was
      highly significant (P = 0.009). CONCLUSION: Our results indicate that Ser482
      homozygotes may be most capable of improving cardiorespiratory fitness when
      physically active, and that Gly482Ser may explain some of the between-person
      variance previously reported in cardiorespiratory adaptation after exercise
      training.

PMID- 14652495
TI  - Potassium potently relaxes small rat skeletal muscle arteries.
AB  - INTRODUCTION: Skeletal muscle contraction elicits an explosive rise in
      interstitial potassium (K+) concentration. K+ has been considered as one of the
      most potent vasoactive metabolites in skeletal muscle arterioles. Studies on
      isolated blood vessels report large relaxations when extracellular [K+] is
      increased up to 10 mM. We studied the effects of smaller and physiologically more
      relevant increases in [K+] (adding 1, 2, and 3 mM) and compared them with
      relaxations induced by the endothelium derived hyperpolarizing factor (EDHF).
      METHODS: Rat gluteal arteries were isolated and mounted in an organ bath for
      isometric tension recording. After precontraction with norepinephrine,
      acetylcholine or K+ was added in control conditions, after removal of the
      endothelium or in the presence of ouabain or Ba2+. RESULTS: Application of 1, 2,
      or 3 mM K+ induced large vasodilations (up to 75.4% with 3 mM) (N = 40), which
      were more sustained at the higher concentrations. Removal of the vascular
      endothelium had no effect on this relaxation. Inhibition of the Kir channels with
      Ba2+ did not alter the K+-induced relaxations, although it significantly
      inhibited the EDHF-mediated relaxation. Incubation with ouabain significantly
      decreased the K+- and EDHF-induced relaxation. Simultaneous application of Ba2+
      and ouabain totally abolished both K+- and EDHF-induced responses. CONCLUSION:
      Even small increases in extracellular K+ concentration elicit large endothelium
      independent and ouabain-sensitive relaxations in small skeletal muscle arteries.
      The fact that both K+- and EDHF-induced vasorelaxations show similar
      characteristics indicates that K+ might be the EDHF in this type of artery.

PMID- 14652496
TI  - Training-specific muscle architecture adaptation after 5-wk training in athletes.
AB  - PURPOSE: This study examined changes in the muscle size, muscle architecture,
      strength, and sprint/jump performances of concurrently training athletes during 5
      wk of "altered" resistance training (RT). METHODS: Eight female and 15 male
      athletes performed 4 wk of sprint, jump, and resistance training in addition to
      their sports training (standardization) before adopting one of three different
      programs for 5 wk: 1) squat lift training (SQ, N = 8) with sprint/jump training;
      2) forward hack squat training (FHS, N = 7) with sprint/jump training; or 3)
      sprint/jump training only (SJ, N = 8). Muscle size, fascicle angle, and fascicle
      length of the vastus lateralis (VL) and rectus femoris (RF) muscles (using
      ultrasound procedures) as well as 20-m sprint run, vertical jump, and strength
      performance changes were examined. RESULTS: A small increase in VL fascicle angle
      in SQ and FHS was statistically different to the decrease in SJ subjects (P <
      0.05 at distal, P < 0.1 at proximal). VL fascicle length increased for SJ only (P
      < 0.05 at distal, P < 0.1 at proximal) and increased in RF in SQ subjects (P <
      0.05). Muscle thickness of VL and RF increased in all training groups (P < 0.05)
      but only at proximal sites. There were no between-group differences in squat,
      forward hack squat, or isokinetic strength performances, or in sprint or jump
      performances, despite improvements in some of the tests across the groups.
      CONCLUSIONS: Significant muscle size and architectural adaptations can occur in
      concurrently training athletes in response to a 5-wk training program. These
      adaptations were possibly associated with the force and velocity characteristics
      of the training exercises but not the movement patterns. Factors other than, or
      in addition to, muscle architecture must mediate changes in strength, sprint, and
      jump performance.

PMID- 14652497
TI  - Glucocorticoid receptor and ubiquitin expression after repeated eccentric
      exercise.
AB  - INTRODUCTION/PURPOSE: Eccentric exercise causes muscle proteolysis that may be
      attenuated with repeated exercise. Therefore, this study determined the effect of
      repeated bouts of eccentric exercise on ubiquitin (UBI), ubiquitin conjugating
      enzyme (E2), and 20S proteasome (20S) and glucocorticoid receptor (GR) mRNA and
      protein expression, myofibrillar protein content, DNA content, caspase-3
      activity, serum skeletal muscle troponin-I (sTnI) and cortisol (CORT), and muscle
      strength. METHODS: Nine males underwent two identical eccentric exercise bouts
      (BT1 and BT2) 3 wk apart involving seven sets of 10 repetitions at 150% one
      repetition maximum of the dominant knee extensors. Blood and muscle biopsy
      samples were obtained before and at 6 and 24 h postexercise whereas muscle
      strength was assessed before and at 24, 48, and 72 h postexercise. Data were
      analyzed with separate 2 x 3 and 2 x 4 factorial ANOVA (P < 0.05). RESULTS:
      Decrements in strength and increased soreness occurred at 24 and 48 h
      postexercise for both bouts (P < 0.05); however, the changes for BT1 were greater
      than BT2. Serum CORT and sTnI were greater immediately after and at 6, 24, and 48
      h postexercise for both bouts; however, the differences in BT1 were greater than
      BT2 (P < 0.05). Caspase-3 activity and the mRNA and protein levels of UBI, E2,
      20S, and GR were increased at 6 and 24 h postexercise, and these differences were
      greater for BT1 than BT2 (P < 0.05). For BT1, DNA and myofibrillar protein
      content decreases were apparent at 24 h postexercise (P < 0.05) but not in BT2.
      CONCLUSION: These results indicate that muscle injury occurring from an initial
      bout of eccentric exercise seems to decrease muscle strength and myofibrillar
      protein, possibly due to apoptosis and up-regulation of glucocorticoid receptor
      mediated increases in UBI-proteolytic pathway activity, all of which appear to be
      tempered with a repeated eccentric exercise bout.

PMID- 14652498
TI  - A dietary supplement attenuates IL-6 and CRP after eccentric exercise in
      untrained males.
AB  - PURPOSE: This study investigated the effects of a dietary supplement on exercise
      induced markers of cell damage and the inflammatory mediators C-reactive protein
      (CRP) and interleukin-6 (IL-6). METHODS: The supplement contained mixed
      tocopherols, flavonoids, and docosahexaenoate. Forty healthy, nonsmoking,
      untrained males (aged 18-35 yr) were randomly assigned to receive either the
      supplement (N = 20) or placebo (N = 20) during the 14-d experimental protocol.
      Blood samples were collected on day 0 (baseline), day 7 (eccentric exercise
      induced injury), day 10, and day 14. OBJECTIVE: Markers of cell damage (creatine
      kinase (CK) and lactate dehydrogenase (LDH)) and inflammation IL-6 and CRP were
      assessed at these time points in conjunction with subjective range of motion
      (ROM) and perceived pain measurements. Statistical analyses were conducted using
      nonparametric methods (P < 0.05). RESULTS: Eccentric arm curl exercise was used
      to induce an acute phase injury response as evidenced by significant (P < 0.0001)
      increases in CK, LDH, and pain, as well as a decreased range of motion 3 d after
      the exercise. There were no significant differences between groups in CK and LDH
      responses. In contrast, there were significant group differences for IL-6 (P =
      0.008) and CRP (P = 0.003). At day 10, by Mann-Whitney U test of changes, the
      placebo group had significantly greater increases in IL-6 and CRP than the
      treatment group (P = 0.05 and P < 0.01), respectively. CONCLUSION: This study
      suggested that exercise-induced inflammation, evaluated by changes in IL-6 and
      CRP, was significantly reduced by the dietary supplement.

PMID- 14652499
TI  - Effect of school age sports on leisure time physical activity in adults: The
      CORDIS Study.
AB  - PURPOSE: Data evaluating the impact of various types of childhood physical
      activity on adult leisure time physical activity (LTPA) are inconsistent. The
      purpose of this study was to evaluate the influence of organized childhood
      sporting activities on LTPA as an adult in a cohort of industrial workers.
      METHODS: The frequency of current LTPA, defined as a half hour or more of
      activity at least once per week, of 3687 industrial workers in the Cardiovascular
      Occupational Risk Factors in Israel Study (CORDIS) cohort was the outcome
      variable. We analyzed the association of organized school age sports with adult
      LTPA, using a multiple logistic regression model, after adjusting for
      sociodemographic variables including current occupational factors. RESULTS:
      Participating in organized school age sporting activities predicted LTPA as an
      adult [adjusted odds ratio (OR) 3.55, 95% confidence intervals (95% CI) 2.97
      4.23]. This association was consistent in the various subgroups of marital
      status, age, smoking, shift work, body mass index, and religious observance.
      CONCLUSIONS: Organized school age sporting activities influenced future LTPA in
      this cohort. Attempts to promote these activities may lead to increased levels of
      LTPA in adults.

PMID- 14652500
TI  - Quadriceps activation in closed and in open kinetic chain exercise.
AB  - PURPOSE: For treatment of various knee disorders, muscles are trained in open or
      closed kinetic chain tasks. Coordination between the heads of the quadriceps
      muscle is important for stability and optimal joint loading for both the
      tibiofemoral and the patellofemoral joint. The aim of this study was to examine
      whether the quadriceps femoris muscles are activated differently in open versus
      closed kinetic chain tasks. METHODS: Ten healthy men and women (mean age 28.5 +/-
      0.7) extended the knees isometrically in open and closed kinetic chain tasks in a
      reaction time paradigm using moderate force. Surface electromyography (EMG)
      recordings were made from four different parts of the quadriceps muscle. The
      onset and amplitude of EMG and force data were measured. RESULTS: In closed chain
      knee extension, the onset of EMG activity of the four different muscle portions
      of the quadriceps was more simultaneous than in the open chain. In open chain,
      rectus femoris (RF) had the earliest EMG onset while vastus medialis obliquus was
      activated last (7 +/- 13 ms after RF EMG onset) and with smaller amplitude (40 +/
      30% of maximal voluntary contraction (MVC)) than in closed chain (46 +/- 43%
      MVC). CONCLUSIONS: Exercise in closed kinetic chain promotes more balanced
      initial quadriceps activation than does exercise in open kinetic chain. This may
      be of importance in designing training programs aimed toward control of the
      patellofemoral joint.

PMID- 14652501
TI  - MMG and EMG responses during 25 maximal, eccentric, isokinetic muscle actions.
AB  - PURPOSE: The purpose of this study was to examine the patterns of the
      mechanomyographic (MMG) and electromyographic (EMG) amplitude responses of the
      vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) during 25
      maximal, eccentric, isokinetic muscle actions. METHODS: Seven healthy adult
      females (22.1 +/- 2.4 yr) completed 25 maximal, eccentric muscle actions on a
      calibrated Cybex 6000 isokinetic dynamometer. EMG and MMG signals were obtained
      from the VL, RF, and VM during this test, and polynomial regression models were
      used to examine the relationships for normalized torque, EMG amplitude, and MMG
      amplitude versus repetition number. RESULTS: There was a cubic relationship (P <
      0.05) between torque and repetition number. EMG amplitude demonstrated a positive
      linear relationship (P < 0.05) for the VL, a quadratic relationship (P < 0.05)
      for the RF, and no relationship (P > 0.05) for the VM over the 25 repetitions.
      MMG amplitude demonstrated a negative linear relationship (P < 0.05) for both the
      VL and VM, and a cubic relationship (P < 0.05) for the RF over the 25
      repetitions. CONCLUSION: The results of the present study demonstrated
      differences between the VL, RF, and VM muscles for the patterns of EMG and MMG
      responses across the 25 maximal, eccentric muscle actions. These findings
      suggested that there are muscle-specific motor control strategies during repeated
      eccentric, isokinetic muscle actions.

PMID- 14652502
TI  - Influence of adducting and abducting muscle forces on the subacromial space
      width.
AB  - PURPOSE: Strengthening of the shoulder depressors is an important component in
      the treatment of impingement syndrome. However, the quantitative effect of
      various muscle forces on the width of the subacromial space has never been
      demonstrated in vivo. Therefore, the purpose of this study was to analyze the
      influence of adducting and abducting muscle forces on the subacromial space width
      in healthy volunteers in various arm positions. METHODS: The shoulders of 12
      healthy volunteers were imaged with an open MR system at 30 degrees, 60 degrees,
      90 degrees, 120 degrees, and 150 degrees of arm elevation under both isometric
      adducting and abducting muscle activity (15 N). After segmentation and three
      dimensional reconstruction of anatomically relevant structures, the minimal
      spatial acromiohumeral and claviculohumeral distances were quantified. RESULTS:
      Adducting muscle forces led to a significant increase of the acromiohumeral
      distance in all arm positions (P < 0.01), varying from 32% (30 degrees ) to 138%
      (90 degrees ) relative to abducting muscle forces. The claviculohumeral distance
      showed an increase of 9% (30 degrees ) to 24% (90 degrees ), this increase being
      also statistically significant at all positions (P < 0.05). During elevation of
      the arm (30-120 degrees ), the absolute subacromial space width was reduced
      significantly (P = 0.001) by 30% under isometric contraction of the adductors
      compared with 53% (P = 0.001) under activation of the abductors. CONCLUSION: This
      in vivo study shows for the first time that adducting muscle forces lead to a
      significant increase of the subacromial space width compared with abducting
      muscle activity. In the future, this technique and data can be used to
      objectively quantify the effect of physical therapy protocols focused on
      increasing the depressor effect of adducting muscles in the postoperative and
      conservative treatment of impingement syndrome of the shoulder.

PMID- 14652503
TI  - Effect of inverted orthoses on lower-extremity mechanics in runners.
AB  - INTRODUCTION: Foot orthoses are recommended for individuals with injuries
      associated with abnormal lower-extremity mechanics. However, the biomechanical
      effect of these devices is not completely understood. Most clinicians and
      researchers believe that foot orthoses are effective in reducing some aspect of
      rearfoot motion. This is important as many injuries are suggested to be the
      result of increased pronation. Inverted orthoses are a more aggressive treatment
      in those whose symptoms do not respond to standard orthotics. They are likely to
      alter motion in all planes. However, no three-dimensional studies have assessed
      lower-extremity mechanics in individuals wearing inverted orthotics. PURPOSE: The
      purpose of this study was to compare the three-dimensional kinematics and
      kinetics of the rearfoot and knee during running while varying orthotic
      intervention. METHODS: Eleven subjects were initially fitted with standard foot
      orthoses and then with inverted orthoses. Three-dimensional kinematic and kinetic
      data were collected for conditions of no orthoses, standard orthoses, and
      inverted orthoses. RESULTS: There were no differences between conditions in peak
      rearfoot eversion or rearfoot eversion excursion. Peak rearfoot inversion moment
      and work were significantly reduced (P = 0.045 and P < 0.001, respectively) in
      the inverted orthotic condition suggesting a decreased demand on the soft tissue
      structures that control eversion. Significant differences were seen in tibial
      rotation (P = 0.043), knee adduction (P = 0.035), and knee abduction moment (P <
      0.001) in the inverted orthotic condition, suggesting alterations were made
      further up the kinetic chain. CONCLUSIONS: The differences in kinetic parameters
      at the rearfoot may result in fewer injuries of the rearfoot soft tissue
      structures when using inverted orthotics. These alterations in lower-extremity
      mechanics associated with inverted orthoses provide clinicians some evidence for
      prescribing this device.

PMID- 14652504
TI  - Theoretical study of the effect of ball properties on impact force in soccer
      heading.
AB  - PURPOSE: The objective of this study was to theoretically model, based on the
      Hertz contact theory, the impact force and contact time, as well as the linear
      and angular head accelerations during heading in children using two neck
      stiffness conditions (infinite and negligible stiffness). METHODS: The following
      mathematical model inputs were obtained: elastic modulus and mass of size three,
      four, and five balls at inflation pressures of 10, 12, and 14 psi, head modulus,
      head mass, head length, head and trunk moment of inertia, and the precontact ball
      velocity. The model outputs consisted of linear and angular head acceleration,
      impact force, contact time between the ball and head, and head impact criteria
      (HIC) all at the point of impact. Head mass and length were obtained as a
      percentage of body weight and height, respectively, based on age. RESULTS: With
      an increase in head mass, there is a decrease in the linear and angular head
      acceleration. With an increase in ball size, for the same head mass, there is an
      increase in the contact time between the head and the ball. Changing ball
      inflation pressure has little effect on the impact characteristics. Infinite neck
      stiffness decreased linear and angular head acceleration and HIC. CONCLUSION:
      Head mass and ball size have an effect on linear and angular head acceleration
      and contact time, respectively, whereas ball inflation pressure has a minimal
      effect on the impact characteristics. These results indicate that children should
      be restricted to using the appropriate ball for their age. Smaller head size
      within an age group is an underemphasized though important identifier of a
      player's injury risk.

PMID- 14652505
TI  - The effects of klapskate hinge position on push-off performance: a simulation
      study.
AB  - PURPOSE: The introduction of the klapskate in speed skating confronts skaters
      with the question of how to adjust the position of the hinge in order to maximize
      performance. The purpose of this study was to reveal the constraint that
      klapskate hinge position imposes on push-off performance in speed skating.
      METHOD: For this purpose, a model of the musculoskeletal system was designed to
      simulate a simplified, two-dimensional skating push off. To capture the essence
      of a skating push off, this model performed a one-leg vertical jump, from a
      frictionless surface, while keeping its trunk horizontally. In this model,
      klapskate hinge position was varied by varying the length of the foot segment
      between 115 and 300 mm. With each foot length, an optimal control solution was
      found that resulted in the maximal amount of vertical kinetic and potential
      energy of the body's center of mass at take off (Weff). RESULTS: Foot length was
      shown to considerably affect push-off performance. Maximal Weff was obtained with
      a foot length of 185 mm and decreased by approximately 25% at either foot length
      of 115 mm and 300 mm. The reason for this decrease was that foot length affected
      the onset and control of foot rotation. This resulted in a distortion of the
      pattern of leg segment rotations and affected muscle work (Wmus) and the efficacy
      ratio (Weff/Wmus) of the entire leg system. CONCLUSION: Despite its simplicity,
      the model very well described and explained the effects of klapskate hinge
      position on push off performance that have been observed in speed-skating
      experiments. The simplicity of the model, however, does not allow quantitative
      analyses of optimal klapskate hinge position for speed-skating practice.

PMID- 14652506
TI  - Prior heavy exercise enhances performance during subsequent perimaximal exercise.
AB  - PURPOSE: To test the hypothesis that prior heavy exercise increases the time to
      exhaustion during subsequent perimaximal exercise. METHODS: Seven healthy males
      (mean +/- SD 27 +/- 3 yr; 78.4 +/- 0.7 kg) completed square-wave transitions from
      unloaded cycling to work rates equivalent to 100, 110, and 120% of the work rate
      at VO2peak (W-[VO2peak) after no prior exercise (control, C) and 10 min after a 6
      min bout of heavy exercise at 50% Delta (HE; half-way between the gas exchange
      threshold (GET) and VO2peak), in a counterbalanced design. RESULTS: Blood
      [lactate] was significantly elevated before the onset of the perimaximal exercise
      bouts after prior HE (approximately 2.5 vs approximately 1.1 mM; P < 0.05). Prior
      HE increased time to exhaustion at 100% (mean +/- SEM. C: 386 +/- 92 vs HE: 613
      +/- 161 s), 110% (C: 218 +/- 26 vs HE: 284 +/- 47 s), and 120% (C: 139 +/- 18 vs
      HE: 180 +/- 29 s) of W-VO2peak, (all P < 0.01). VO2 was significantly higher at 1
      min into exercise after prior HE at 110% W-VO2peak (C: 3.11 +/- 0.14 vs HE: 3.42
      +/- 0.16 L x min(-1); P < 0.05), and at 1 min into exercise (C: 3.25 +/- 0.12 vs
      HE: 3.67 +/- 0.15; P < 0.01) and at exhaustion (C: 3.60 +/- 0.08 vs HE: 3.95 +/-
      0.12 L x min(-1); P < 0.01) at 120% of W-VO2peak. CONCLUSIONS: This study
      demonstrate that prior HE, which caused a significant elevation of blood
      [lactate], resulted in an increased time to exhaustion during subsequent
      perimaximal exercise presumably by enabling a greater aerobic contribution to the
      energy requirement of exercise.

PMID- 14652507
TI  - Heart rate recovery from submaximal exercise in boys and girls.
AB  - PURPOSE: To examine the changes in heart rate (HR) after two different submaximal
      exercise bouts in boys and girls. METHODS: Eleven boys (10.5 +/- 1.0 yr) and 10
      girls (10.8 +/- 0.7 yr) participated in this study. Each child completed an
      initial graded exercise test to determine peak VO2. On subsequent and separate
      days, a 5-min submaximal exercise bout on a cycle ergometer was performed. One
      bout was conducted at 70 W, and the other bout corresponded to an intensity of 85
      90% of peak VO2. VO2 and HR were measured during and after (1 min and 3 min). HR
      recovery responses from each submaximal exercise bout were analyzed using a group
      by time ANOVA, and Pearson-product correlations were determined between resting
      HR, peak VO2, and postexercise HR responses. RESULTS: HR in the boys was lower at
      the end of exercise and the first minute of recovery versus girls but not at the
      3rd min of recovery. There were no differences in HR recovery after the relative
      exercise bout. Resting HR was significantly correlated with postexercise HR from
      both bouts (r = 0.52-0.69), whereas peak VO2 did not correlate to postexercise
      HR. ANCOVA using resting HR as the covariate eliminated the gender different
      noted with the recovery from the 70-W bout. CONCLUSIONS: In summary, postexercise
      HR responses differed between boys and girls when submaximal exercise was
      performed at an absolute work rate. When exercise was performed at a relative
      intensity, HR recovery responses were similar between the two groups. Resting HR
      appears to account for variations in postexercise HR better than peak VO2.

PMID- 14652508
TI  - Modeling the relationship between velocity and time to fatigue in rowing.
AB  - INTRODUCTION: Several mathematical models describe the relationship between
      velocity and time to fatigue. PURPOSE: The purposes of this study were to
      evaluate different critical velocity (V(critical)) models applied to rowing
      ergometry and to investigate prediction of performance time in a 2000-m race
      based on results from shorter trials. METHODS: Sixteen men performed seven rowing
      ergometer tests. Velocity and time to fatigue data from the 200-m (approximately
      0.5 min) to 1200-m (approximately 3 min) trials and from the 200-m to 2000-m
      (approximately 6.5 min) trials were fit to a two-parameter hyperbolic model, a
      three-parameter hyperbolic model, and a three-parameter exponential model.
      RESULTS: Including data from the 2000-m trial generally resulted in higher R2 and
      smaller SEE. V(critical) from the three versions of the two-parameter model were
      4.71 +/- 0.28 m x s(-1), 4.80 +/- 0.27 m x s(-1), and 5.04 +/- 0.24 m x s(-1) (P
      < 0.001). The two three-parameter models had high R2 (0.991 and 0.990,
      respectively) and generated parameter estimates that appeared reasonable. Time
      for a 2000-m race was predicted better using the two-parameter model (r > 0.974)
      than using the three-parameter models (r = 0.820-0.870). CONCLUSION: It is
      necessary to include the relatively long 2000-m predicting trial to describe
      accurately the velocity-time relationship in rowing. The two-parameter model may
      be useful in predicting time for a 2000-m race but is not otherwise appropriate
      for modeling when predicting trials of <1 min duration are included. Choice of
      model and duration of trials must be considered when using mathematical modeling
      to derive V(critical) and other parameters in rowing.

PMID- 14652509
TI  - Scaling behavior of VO2peak in trained wheelchair athletes.
AB  - PURPOSE: To examine the scaling behavior of peak oxygen uptake (VO2peak) in
      wheelchair athletes, adjusting for known covariates. METHODS: Body mass, VO2peak,
      and an estimate of adiposity (sum of four skinfolds) were determined in a sample
      of 45 highly trained wheelchair basketball and racing athletes. The participants
      were classified as possessing either "high" or "low" trunk stability and balance
      using recognized sporting classifications. A wheelchair ergometer was used to
      obtain the VO2peak measurements. The relationship between VO2peak and body mass
      was obtained via a nonlinear allometric model with the sum of four skinfolds,
      trunk stability and balance, and chronological age entered as covariates.
      RESULTS: The point estimate exponent for body mass was 0.82 (95% CI, 0.54-1.10).
      After controlling for the influence of body mass, adiposity, and age, the
      wheelchair athletes with greater trunk stability and balance had on average an
      11% greater VO2peak. The regression model explained 54% of the sample variance in
      VO2peak. CONCLUSIONS: The obtained mass exponent of 0.82 is congruent with that
      predicted from the multiple-causes allometric cascade model and consideration of
      the physiological characteristics of spinal cord injured athletes. To compare the
      body size-independent VO2peak values of athletes within the study sample, the
      mass exponent of 0.82 may be adopted (i.e., mL x kg(-0.82) x min(-1)). The
      uncertainty in the point estimate, reflected in the relatively wide 95% CI,
      highlights the need for further research with larger samples to increase the
      precision of estimation.

PMID- 14652510
TI  - Assessment of physical activity by telephone interview versus objective
      monitoring.
AB  - PURPOSE: To compare different methods of quantifying time in physical activity
      (PA). METHODS: Twenty-five participants (12 male, 13 female) volunteered to be
      monitored for seven consecutive days, during which different PA patterns were
      measured by the simultaneous heart-rate motion sensor technique (HR+M). At the
      end of the 7th day, participants completed questions taken from the 2001
      Behavioral Risk Factor Surveillance System (BRFSS) PA module telephone survey, in
      which they recalled the amount of time spent walking, and in moderate and
      vigorous activities. The results of the BRFSS PA module were then compared with
      those of the HR+M. RESULTS: No significant group differences were found in the
      amount of time spent in moderate and vigorous activities between methods.
      However, individual differences were greater for time spent in moderate
      activities (SE +/- 7.36 min x d(-1); range -70 to 77 min x d(-1)) than for time
      spent in vigorous activities (SE +/- 3.57 min x d(-1); range -39 to 33 min x d(
      1). Spearman correlation coefficients between the HR+M and the BRFSS were
      significant for vigorous activities (r = 0.54, P < 0.01). There was 80% agreement
      between the two methods of classifying individuals who either: (a) met the
      recommendations (through moderate and/or vigorous PA) or (b) did not meet the
      recommendations. CONCLUSION: The BRFSS and HR+M methods yielded similar group
      estimates of PA, but individual assessments of moderate activity differed more
      than those of vigorous activity. BRFSS estimations of group compliance with
      national PA recommendations were similar to those of the HR+M.

PMID- 14652511
TI  - Doubtful validity of the Yo-Yo intermittent recovery test.

PMID- 14652513
TI  - Epidermolysis bullosa: identification and treatment.

PMID- 14652514
TI  - Diabetes, nutrition, and wound healing.

PMID- 14652515
TI  - Diagnosis=medical necessity=payment.

PMID- 14652517
TI  - Prevalence of lower-limb ulceration: a systematic review of prevalence studies.
AB  - OBJECTIVE: To determine the prevalence of leg ulcers reported in the literature.
      DESIGN: A systematic review of prevalence studies of lower-limb ulceration in the
      adult population was conducted. Critical appraisal of the research papers was
      guided by published standards for methodologic review of prevalence studies,
      which were modified to address the issues related to leg ulcers. MAIN RESULTS:
      Twenty-two reports of prevalence studies were identified. Eight population-based
      prevalence studies used clinical validation and reported prevalence rates of open
      ulcers ranging from 0.12% to 1.1% of the population; the prevalence rate of open
      or healed ulcers was reported to be 1.8%. Seven population-based studies without
      clinical validation reported prevalence rates of open ulcers ranging from 0.12%
      to 0.32% of the population. Differences in the populations studied, study design,
      ulcer definition, ulcer etiology, inclusion of foot ulcers, method of clinical
      assessment, and clinical validation of ulcer cases indicate that it is
      inappropriate to pool the estimates of prevalence. In most studies that
      considered age and sex, the prevalence of ulcers increased with age and was
      higher for women. CONCLUSIONS: Better-quality prevalence studies are needed.
      These studies should clearly define the populations being studied, include large
      numbers of individuals and total populations, provide a clear definition of an
      ulcer, describe case identification procedures, and clinically confirm the
      presence of ulcers.

PMID- 14652516
TI  - Pressure ulcers and the transition to long-term care.
AB  - OBJECTIVE: To estimate the prevalence of pressure ulcers among newly admitted
      residents of long-term-care facilities and to determine whether patients admitted
      from hospitals had a higher prevalence than those admitted from home or other
      settings. DESIGN: Prospective cohort study conducted between 1992 and 1995.
      SETTING: 59 long-term-care facilities in Maryland. PARTICIPANTS: 2015 residents
      aged 65 years and older newly admitted to participating long-term-care
      facilities. MAIN OUTCOME MEASURE: Stage II, III, or IV pressure ulcer, first
      mentioned in the long-term-care facility's chart within 2 days of admission. MAIN
      RESULTS: Of the 2015 residents studied, 208 (10.3%) had 1 or more pressure ulcers
      on admission to a long-term-care facility. The proportion of patients with 1 or
      more pressure ulcers was 11.9% among those admitted from a hospital and 4.7%
      among those not admitted from a hospital (P<.001). In multivariable analysis,
      admission from a hospital was significantly associated with pressure ulcer
      prevalence on admission (odds ratio, 2.2; 95% confidence interval, 1.3-3.7). A
      lower prevalence of pressure ulcers on admission was significantly associated
      with being white; a higher prevalence was associated with being chairbound or
      bedridden, being underweight, and having fecal incontinence. CONCLUSION:
      Admission to a long-term-care facility from a hospital is an important marker for
      higher pressure ulcer risk. The identification of pressure ulcer risk factors is
      essential to the implementation of prevention activities, ensuring that
      appropriate interventions are targeted to the residents who are most likely to
      benefit.

PMID- 14652518
TI  - Randomized clinical trial comparing 2 support surfaces: results of the Prevention
      of Pressure Ulcers Study.
AB  - OBJECTIVE: To determine whether a viscoelastic polymer (energy absorbing) foam
      mattress was superior to a standard hospital mattress for pressure ulcer
      prevention and to analyze the cost-effectiveness in comparison with standard
      hospital mattresses. DESIGN: Unblinded, randomized, prospective trial. SETTING:
      Elderly acute care, rehabilitation, and orthopedic wards at 3 hospitals in the
      United Kingdom. PARTICIPANTS: 1168 patients at risk of developing pressure ulcers
      (Waterlow score, 15 to 20), with a median age of 83 years (25th to 75th
      percentile range, 79-87). INTERVENTIONS: Participants were allocated to either
      the experimental equipment (CONFOR-Med mattress/cushion combination) or a
      standard mattress/cushion combination; all were given standard nursing care.
      Pressure areas were observed daily. MAIN OUTCOME MEASURE: Development of
      nonblanching erythema. RESULTS: A significant decrease in the incidence of
      blanching erythema (26.3% to 19.9%; P =.004) and a nonsignificant decrease in the
      incidence of nonblanching erythema occurred in participants allocated to the
      experimental equipment. However, when the survival curve plots were analyzed at 7
      days, both categories showed statistically significant decreases (P =.0015 and P
      =.042, respectively). Participants on standard equipment had a relative odds
      ratio of 1.36 (95% confidence interval [CI], 1.10-1.69) for developing blanching
      erythema or worse and 1.46 (95% CI, 0.90-1.82) for developing nonblanching
      erythema or worse. To prevent nonblanching erythema, the number needed to treat
      (NNT) was 41.9 (95% CI, -82.6-15.3). To prevent any erythema (blanching or
      nonblanching), the NNT was 11.5 (95% CI, 41.6-9.3). Participants with blanching
      or nonblanching erythema were significantly less mobile than participants with
      normal skin and more likely to have worsening mobility (P <.001). For
      participants with similar pressure ulcer status, mattress type was not associated
      with difference in mobility. CONCLUSIONS: Regardless of prevention routine,
      pressure ulcers occur. In this study, the experimental equipment showed
      statistical significance to standard equipment for prevention of blanching
      erythema; significance was not achieved for nonblanching erythema. Trend and
      survival analysis show that a larger study is required to determine whether this
      nonsignificant difference is genuine.

PMID- 14652519
TI  - Optimizing cancer care in the elderly: progress in geriatric oncology.

PMID- 14652520
TI  - Guidelines for the treatment of elderly cancer patients.
AB  - BACKGROUND: The management of elderly patients with cancer is influenced by
      several factors that can vary widely among aging individuals. As the proportion
      of elderly individuals increases, the need for specific care guidelines for this
      population is critical. The National Comprehensive Cancer Network (NCCN) has
      developed guidelines to address these factors when formulating optimal treatment
      regimens for elderly patients and to avoid significant toxicity and maintain
      their quality of life. METHODS: Factors that influence the appropriate treatment
      choices for the elderly, such as functional status, comorbidity, polypharmacy,
      and the presence of anemia, are reviewed, and the guidelines developed by the
      NCCN for treatment elderly patients are discussed. RESULTS: The guidelines
      address these factors when defining the goal of therapy and formulating
      individualized treatment approaches for the elderly to provide optimal care for
      these patients, avoid significant toxicity, and maintain their quality of life.
      CONCLUSIONS: The goal of therapy must be clearly defined, whether survival,
      remission, cure, or palliation of symptoms. Enrollment of elderly cancer patients
      onto clinical trials is encouraged so the guidelines can be validated.

PMID- 14652522
TI  - Studies of comprehensive geriatric assessment in patients with cancer.
AB  - BACKGROUND: The comprehensive geriatric assessment (CGA) has been developed to
      individually assess the health status of older patients. METHODS: This article
      reviews the findings regarding the impact of a comprehensive geriatric assessment
      (CGA) on treatment and outcomes in patients with cancer. RESULTS: Several
      geriatric variables have been linked with the prognosis of older cancer patients,
      thus challenging the role of ECOG performance status in this population. A CGA
      may detect multiple untreated or undertreated problems in cancer patients.
      Although results are preliminary, some studies suggest that CGA may influence
      cancer treatment decisions and have a prognostic impact on patients with this
      disease. CONCLUSIONS: More work is needed to simplify such assessments to make
      them more feasible and to determine when they should be used during a patient's
      clinical course.

PMID- 14652521
TI  - Comprehensive geriatric assessment.
AB  - BACKGROUND: As an adjunct to the general and cancer-specific clinical and
      diagnostic examinations, comprehensive geriatric assessment (CGA) is an integral
      tool that examines factors affecting the course of disease and the outcome of
      treatment. The principal areas of focus of the CGA include the patient's
      functional, physical, mental, emotional, pharmacotherapeutic, and socioeconomic
      status. METHODS: We describe the role of CGA in the identification and management
      of frail elderly patients. The literature is reviewed to outline the components,
      programmatic configurations, and process of CGA. Information from systematic
      reviews of clinical trials of different CGA program models is summarized, and
      observations relating to the research agenda concerning the applicability of CGA
      and CGA principles to management of older cancer patients are discussed. RESULTS:
      Since age itself is not predictive of outcome in an elderly cancer patient, the
      CGA helps to distinguish between elderly patients who should be treated with
      intent to cure and those who will benefit from clinical oncologic and geriatric
      co-management. CONCLUSIONS: A more accurate evaluation of prognostic indicators
      that includes CGA parameters could lead to a higher number of older patients
      being included in clinical cancer trials and being treated effectively in
      practice. It would also identify those who would benefit from gero-oncologic CGA
      and ongoing management aimed at maintaining function and community living.

PMID- 14652523
TI  - Management of acute myelogenous leukemia in the elderly.
AB  - BACKGROUND: Acute myelogenous leukemia (AML) is a hematopoietic neoplasm that
      primarily affects older adults. Despite scientific advances into the
      epidemiologic, genetic, and biological features of AML, this disease remains
      fatal to the majority of patients, particularly older individuals. METHODS: We
      review the biologic and clinical characteristics of AML in the elderly and the
      treatment options that have emerged for them during the past several years.
      RESULTS: Several biologic features of AML differ between older and younger
      individuals. Older patients often have disease that expresses multidrug
      resistance phenotype and cytogenetic abnormalities, which may be responsible in
      large part for the poor outcomes observed in older-aged subgroups. Traditional
      cytotoxic chemotherapy is associated with a low complete response rate and a high
      treatment-related mortality in older patients, which explains in part the poorer
      outcomes in cohorts over 60 years of age. Research into the pathophysiology of
      AML has revealed an abundance of intracellular signaling events that govern
      proliferation and survival of the malignant cell. Such discoveries have promoted
      recognition of new molecular and antigenic targets (eg, Flt-3 kinase, Ras, CD33
      antigen) to which therapeutic development may be aimed. CONCLUSIONS: New
      therapies directed against these unique targets may add to the current arsenal of
      antileukemic regimens and improve response rates and survival in older patients.

PMID- 14652524
TI  - Anemia, cancer, and aging.
AB  - BACKGROUND: Anemia is an issue of concern in the management of older patients
      with cancer. In this age group, the incidence and prevalence of both cancer and
      anemia increase with age. METHODS: The clinical consequences and the management
      of anemia, a common comorbid condition in older patients with cancer, are
      explored. RESULTS: Common causes of chronic anemia include iron deficiency and
      anemia of chronic disease. The prevalence of vitamin B12 deficiency due to
      reduced absorption of food-bound vitamin B12 also increases with aging. Although
      in many cases the cause of anemia is not found, a primary deficiency of
      erythropoietin may be at fault in at least some of these cases since the response
      of erythropoietin to anemia may decrease in individuals over age 70. CONCLUSIONS:
      Anemia should not necessarily be ascribed to cancer or aging. The causes of
      anemia should be pursued and reversed, and hemoglobin levels should be maintained
      at a minimum of 12 g/dL in cancer patients undergoing chemotherapy who are
      responsive to erythropoietin. The reversal of anemia may offset or delay the
      accumulation of catabolic cytokines that may be responsible for functional
      decline in aging individuals.

PMID- 14652525
TI  - Evidence-based use of colony-stimulating factors in elderly cancer patients.
AB  - BACKGROUND: Neutropenia and its complications represent the major dose-limiting
      toxicity of cancer chemotherapy, especially in the elderly. Hematopoietic growth
      factors have been shown to reduce the severity and duration of febrile
      neutropenia (FN) and to sustain chemotherapy dose intensity. METHODS: A
      systematic review was undertaken of studies of the relationship between age and
      the risk of neutropenia and its complications. Recent studies of the "Awareness
      of Neutropenia in Chemotherapy Study Group" related to the impact of age on
      neutropenic complications are also summarized. RESULTS: The risk of FN associated
      with standard regimens increases with age and appears to be greatest during the
      first cycle of chemotherapy. FN continues to have a considerable clinical,
      economic, and quality-of-life impact on affected individuals. The risk of
      mortality associated with hospitalization with FN also increases with age but is
      largely associated with the higher rate of comorbidities observed in the elderly
      population. Despite increasing evidence that elderly patients experience similar
      benefit from cancer chemotherapy, reductions in dose intensity often compromise
      response rates and long-term survival. The hematopoietic growth factors reduce
      the risk of neutropenic events and the need for reduced dose intensity in elderly
      cancer patients. Primary prophylaxis with colony-stimulating factors (CSFs)
      reduces the risk of FN and its complications in elderly patients receiving
      moderately intensive systemic chemotherapy for responsive malignancies. CSFs also
      appear to reduce cost and improve quality of life in selected elderly patients
      receiving chemotherapy. CONCLUSIONS: Primary prophylaxis with CSFs should be
      considered in elderly patients with responsive and potentially curable
      malignancies who receive moderately intensive chemotherapy.

PMID- 14652526
TI  - High-altitude-related disorders--Part I: Pathophysiology, differential diagnosis,
      and treatment.
AB  - As increasing numbers of people choose to sojourn or retire to the mountains,
      high-altitude illness is becoming a pathological phenomenon about which
      healthcare providers should have greater awareness. Hypoxia is the primary cause
      of high-altitude illness, but other stressors on the sympathetic nervous system,
      such as cold and exertion, also contribute to disease development and
      progression. Although variable across persons, symptoms of high-altitude
      disorders usually occur at altitudes over 7000 feet, and typically in 1 of 3
      forms: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), or
      high-altitude pulmonary edema (HAPE). Major symptoms include nausea, poor sleep,
      headache, lassitude, cough, dyspnea on exertion and at rest, ataxia, and mental
      status changes. As a rule, illness occurring at high altitude should be
      attributed to the altitude until proven otherwise. Treatment is best accomplished
      by descent and by oxygen or pharmacologic intervention if necessary. Under no
      circumstances should a person with worsening symptoms of high-altitude illness
      delay descent. As will be discussed in part II of this article, gradual ascent
      and subsequent acclimatization to altitude is the most effective prevention,
      though acetazolamide (Diamox) may be a useful prophylactic measure in some.

PMID- 14652527
TI  - Impact of chronic obstructive pulmonary disease on family functioning.
AB  - PURPOSE: The purpose of this study was to ascertain family dynamics of Finnish
      patients with severe chronic obstructive pulmonary disease (COPD) on the basis of
      Barnhill's framework for healthy family functioning. DESIGN AND METHOD: This
      study used description and comparison and an interview-administered questionnaire
      and survey. SAMPLE: Participants were patients with COPD and their family members
      (n = 65) living in the Tampere University Hospital catchment area. The sample
      consisted of families of home oxygen therapy patients (n = 36) and families of
      inpatients (n = 29). Families consisted of patients and their family members.
      INSTRUMENTS: Data were collected from patients by interview-administered
      questionnaires and from family members by survey. The instrument used was the
      Family Dynamics Measure 2, operationalized and tested by the American Family
      Research Group. RESULTS: Families of home oxygen therapy patients experienced
      significantly more mutuality (P =.03) and made decisions about their illness and
      life significantly more independently (P =.05) than families of inpatients.
      Families of home oxygen therapy patients handled change significantly more
      flexibly (P =.03) than families of inpatients. DISCUSSION: For the most part,
      families of both patient groups functioned well, but overall family functioning
      was clearly better in families of home oxygen therapy patients. The sample
      included some dysfunctional and even severely dysfunctional families. The results
      of this study cannot be generalized beyond the study sample because of the small
      sample size, but they provide suggestions for developing the care of patients
      with COPD and their families.

PMID- 14652528
TI  - Short-term effects of exercise and music on cognitive performance among
      participants in a cardiac rehabilitation program.
AB  - OBJECTIVE: Exercise has been associated with improved cognitive performance among
      patients with coronary artery disease. Music listening has been associated with
      enhanced cognitive functioning among healthy adults. This study evaluated the
      combined influence of exercise and music listening on cognitive performance among
      patients in cardiac rehabilitation (CR). DESIGN AND SETTING: Using a within
      subjects repeated measures design, this study was conducted in an outpatient
      University-based CR facility. SAMPLE: Thirty-three men and women (mean age = 62.6
      +/- 10.5 years) participated in this study. METHODS: Participants completed 1
      exercise session accompanied by music and a second exercise session without
      music. Order of conditions was assigned randomly. Before and after each exercise
      session, participants completed a brief assessment of depression and anxiety, and
      a cognitive test of verbal fluency. RESULTS: The music condition was associated
      with significant improvements in verbal fluency, but the no-music control
      condition was not associated with cognitive change. CONCLUSION: The study
      provides preliminary evidence of the combined benefit of exercise and music
      listening for cognitive performance among patients in CR.

PMID- 14652529
TI  - Cardiovascular risk reductions associated with aggressive lifestyle modification
      and cardiac rehabilitation.
AB  - BACKGROUND: Patients who have been treated for coronary heart disease can enroll
      in traditional cardiac rehabilitation, the Ornish Program, or no rehabilitation
      at all. No study has compared the impact of each on cardiovascular disease risk
      (CVD) factors. METHODS: The current study compared CVD risk changes in post
      coronary artery bypass graft or percutaneous coronary intervention procedure
      patients who participated in the Ornish Heart Disease Reversing Program, a
      traditional cardiac rehabilitation, and a control group that received no formal
      cardiac risk-reduction program. This was a longitudinal, observational study of
      84 patients receiving CVD standard of care who elected to participate in 1 of the
      3 study groups. Assessments of CVD risk factors and anginal severity were
      obtained at baseline, 3 months, and 6 months. RESULTS: Ornish program
      participants had significantly greater reductions in anginal frequency, body
      weight, body mass index, systolic blood pressure, total cholesterol, low-density
      lipoprotein cholesterol, glucose, dietary fat, and increases in complex
      carbohydrates than were documented in the rehabilitation or control groups. The
      control group experienced the greatest reduction in anginal pain severity, but
      also had significantly higher systolic blood pressure, total cholesterol, and low
      density lipoprotein cholesterol. CONCLUSIONS: These findings suggest that CVD
      patients who choose to participate in the Ornish program can experience greater
      improvements in CVD risks than patients who choose to participate in traditional
      cardiac rehabilitation or no formal program.

PMID- 14652530
TI  - Comparative analysis of risk-adjusted bypass surgery stratification models in a
      community hospital.
AB  - BACKGROUND: Quality improvement in health care, which relies on appropriate
      strategies to evaluate and compare provider performance, has spawned the
      propagation of many public report cards or provider profiles for cardiac surgery.
      These risk-adjusted prediction models allow for the computation of a provider's
      expected outcome event rate compared with observed outcome events. The aim of
      this study was to assess the accuracy and reliability of 5 risk-adjusted
      predictive models for mortality in an independent population of patients in a
      community hospital who underwent coronary artery bypass graft surgery. METHODS:
      Five nonproprietary models were selected for evaluation (Parsonnet, Canadian,
      Cleveland, New York, and the Northern New England). RESULTS: The C-statistic for
      the 5 models was 0.752, 0.693, 0.748, 0.735, and 0.722 for the Parsonnet,
      Canadian, Cleveland, New York, and Northern New England models respectively. The
      H-L c2 calibration statistics were 4.948, P =.763; 1.616, P =.899; 11.96, P
      =.035; 10.23, P =.249; and c2 = 12.14, P =.145 for the Parsonnet, Canadian,
      Cleveland, New York, and Northern New England models respectively. CONCLUSIONS:
      Comparing hospital-specific or surgeon-specific mortality/morbidity rates will
      remain a challenge. This analysis reaffirms the concept of risk-adjusting
      outcomes and emphasizes the importance of the risk-adjustment process for CABG
      surgery in a community hospital.

PMID- 14652531
TI  - Correlates of health-related quality of life among lower-income, urban adults
      with congestive heart failure.
AB  - BACKGROUND: Improving health-related quality of life (HRQL) is a primary goal in
      the treatment of patients with congestive heart failure (CHF), yet few studies
      have explored correlates of HRQL among CHF patients. OBJECTIVES: We report on the
      association of demographic and pathophysiologic measures, social-cognitive
      measures, and environmental variables with HRQL as measured by the Kansas City
      Cardiomyopathy Questionnaire (KCCQ), Chronic Heart Failure (CHQ), and a single
      question of perceived overall health (PH). METHODS: Cross-sectional data were
      obtained from the baseline interview and electronic medical records of 212
      patients 50 years of age and older who were enrolled during the first 7 months of
      a medication adherence study. RESULTS: Mean age was 63; 32% were male; 53% were
      black; the mean Charlson comorbidity score was 3.7; and the mean New York Heart
      Association class was 2.1. Correlations between KCCQ and CHQ subscale scores and
      PH ranged from 0.16 to 0.37. Multivariate regression analyses showed that the
      pathophysiologic measures ejection fraction and comorbidity were not associated
      with any of the HRQL measures. Overall PH was associated with greater age and
      more positive health beliefs. Persons of greater age, males, and black
      respondents had higher CHF-specific HRQL scores, as did persons reporting more
      positive health beliefs, greater income, social support, and communication with
      their physician. Variance explained ranged from 14 to 33%. CONCLUSION: These
      cross-sectional data highlight the potential significance of social and
      behavioral factors in CHF-specific HRQL.

PMID- 14652532
TI  - SAM-systolic anterior motion of the anterior mitral valve leaflet post-surgical
      mitral valve repair.
AB  - Systolic anterior motion (SAM) is a postoperative complication experienced by
      patients undergoing mitral valve repair. The incidence of SAM after mitral valve
      repair ranges from 5 to 10%. Early recognition of the signs and symptoms of SAM
      is imperative to the management of these patients. This article presents the
      pathophysiology of mitral valve dysfunction to give the practitioner a clear
      understanding of the dynamics of SAM. This article's main focus is the detection
      and management of SAM and the most current treatment modalities. A case study is
      used to illustrate the complex management necessary for the patient with SAM.

PMID- 14652533
TI  - Dynamic cardiomyoplasty as a biomechanic bridge to heart transplantation.
AB  - We report a heart transplantation that was done 4 years after a dynamic
      cardiomyoplasty operation. The patient was a 42-year-old man. Radionucleide
      ventriculography with technetium 99 m revealed an ejection fraction of 18%. In
      July 1997 he had undergone a dynamic cardiomyoplasty operation. At the first
      postoperative month the left ventricular ejection fraction was 35%. In September
      2000 he presented with heart failure symptoms. In May 2001 he had undergone heart
      transplantation. Postoperative course was uneventful. The failure of
      cardiomyoplasty was probably caused by degeneration of the latissimus dorsi
      muscle. In this case we have learned that muscle viability is lost within 4 years
      after dynamic cardiomyoplasty and heart transplantation is still an option for
      those patients.

PMID- 14652534
TI  - Accrochage.

PMID- 14652535
TI  - Dengue fever: diagnostic importance of a camelback fever pattern.
AB  - We present a case of imported dengue fever in a 52-year-old man acquired during a
      recent trip to Ecuador. Fever in a returning traveler from tropical areas often
      presents a diagnostic problem for clinicians. Our patient presented with severe
      arthralgias and myalgias and had a camelback/saddleback fever pattern accompanied
      by relative bradycardia, which was a clue to the diagnosis. He had conjunctival
      suffusion and the truncal rash, but adenopathy was not present. He also had a
      generalized headache and abdominal pain. Nonspecific laboratory abnormalities
      included leukopenia, lymphopenia, atypical lymphocytes, thrombocytopenia, and
      mildly increased serum transaminases. Clinicians should consider dengue fever in
      the differential diagnosis in travelers returning from dengue fever endemic areas
      of Southeast Asia, Latin America, and Africa. Although early findings are
      nonspecific, a truncal rash accompanied by leukopenia and thrombocytopenia, if
      followed by biphasic fever pattern (ie, camelback/saddleback fever curve with
      relative bradycardia), suggest dengue fever as the primary diagnostic
      consideration.

PMID- 14652541
TI  - The Paris endoscopic classification of superficial neoplastic lesions: esophagus,
      stomach, and colon: November 30 to December 1, 2002.

PMID- 14652542
TI  - Comments on the classification.

PMID- 14652543
TI  - Reflections by an endoscopist.

PMID- 14652544
TI  - History of the endoscopic classification in Japan.

PMID- 14652545
TI  - The commencement and development of studies on discrepancies in pathologic
      diagnosis of early carcinoma of the GI tract.

PMID- 14652546
TI  - The role of EUS for evaluation of mediastinal adenopathy.
AB  - This is one of a series of statements discussing the utilization of GI endoscopy
      in common clinical situations. The Standards of Practice Committee of the
      American Society for Gastrointestinal Endoscopy prepared this text. In preparing
      this guideline, a MEDLINE literature search was performed, and additional
      references were obtained from the bibliographies of the identified articles and
      from recommendations of expert consultants. When little or no data exist from
      well-designed prospective trials, emphasis is given to results from large series
      and reports from recognized experts. Guidelines for appropriate utilization of
      endoscopy are based on a critical review of the available data and expert
      consensus. Further controlled clinical studies are needed to clarify aspects of
      this statement, and revision may be necessary as new data appear. Clinical
      consideration may justify a course of action at variance to these
      recommendations.

PMID- 14652547
TI  - Gastrointestinal endoscopes: May 2003.

PMID- 14652548
TI  - Federal funding of endoscopic research in the United States: 1972-2002.
AB  - BACKGROUND: Funding for research is critical to the determination of appropriate
      applications for endoscopy in clinical practice. We sought to evaluate trends in
      funding provided by the National Institutes of Health (NIH) for endoscopic
      research from 1972 through 2002. METHODS: The NIH database of funded biomedical
      projects for the years 1972 through 2002 was searched using the Computerized
      Retrieval of Information on Scientific Projects (CRISP) and the keyword
      "endoscopy." Grants were included if a start date, title, and/or specific aims
      were available. Grants were classified as primary endoscopy if the title or
      specific aim had an endoscopy focus. Endoscopy funding was compared with other
      nonendoscopic funding for the same period. RESULTS: From 1972 through 2002, 133
      endoscopy-related grant applications were funded and 98 met inclusion criteria.
      Funding for endoscopic research increased from one grant (1972-1982) to 4 grants
      (1983-1992) to 93 grants (1993-2002), a 2325% increase for the 1993-2002 decade
      alone. Despite this increase, there were substantially fewer funded endoscopy
      related applications compared with liver disease (61,804 grants), Helicobacter
      pylori (866 grants), and cardiac catheterization (1547 grants). Among endoscopic
      grants, colorectal cancer projects accounted for the largest portion (34%),
      followed by advanced optical technologies (18%) and Barrett's esophagus (17%).
      CONCLUSIONS: Funding for endoscopic research by the NIH has increased
      dramatically over the past 30 years, but it still lags behind funding in other
      fields. Projects focused on colorectal cancer, Barrett's esophagus, and optical
      technologies were most common among those funded, and the National Cancer
      Institute was the primary source of funding.

PMID- 14652549
TI  - Long-term follow-up of patients with clinically indeterminate suspicion of
      pancreatic cancer and normal EUS.
AB  - BACKGROUND: EUS often is performed because of a clinical suspicion of pancreatic
      cancer when the results of other noninvasive diagnostic tests are indeterminate.
      The aim of this study was to determine the true negative predictive value of a
      normal EUS in a cohort of patients with an indeterminate suspicion of pancreatic
      cancer by obtaining long-term follow-up information. METHODS: Patients referred
      for EUS of the pancreas for the following indications were identified: elevated
      carbohydrate-associated antigen (CA 19-9) without other definitive evidence of
      pancreatic cancer, subtle abnormalities on CT of the pancreas, and unexplained
      abdominal pain and/or weight loss. Endoscopy procedure reports, as well as
      inpatient and outpatient records were obtained. In addition, referring
      physicians, as well as patients, were contacted to acquire adequate follow-up
      information. RESULTS: A total of 80 patients were included in the study. Follow
      up of at least 6 months was obtained for 76 (95%) patients (mean follow-up 23.9
      months). No patient with a normal EUS of the pancreas developed pancreatic cancer
      or required pancreatic surgery during the follow-up period. One patient in whom a
      diagnosis of chronic pancreatitis was made by EUS subsequently was found to have
      pancreatic cancer at surgery. CONCLUSIONS: A normal EUS of the pancreas in the
      setting of subtle radiologic findings, serologic abnormalities, and/or
      nonspecific symptoms definitively rules out the presence of pancreatic cancer.

PMID- 14652550
TI  - Early colonoscopy for acute lower GI bleeding predicts shorter hospital stay: a
      retrospective study of experience in a single center.
AB  - BACKGROUND: Appropriate management of lower-GI hemorrhage remains controversial
      largely because outcomes data are lacking. It is our hypothesis that clinical
      factors, such as comorbidity, hemodynamic instability, and timing of colonoscopy,
      are associated with hospital lengths of stay. METHODS: Medical records of
      patients hospitalized for lower-GI hemorrhage from 1993 to 2000 were reviewed and
      abstracted, and a Cox regression model was constructed to explore associations
      between time to discharge (i.e., length of stay) and clinical parameters.
      RESULTS: A total of 565 hospitalizations for acute lower-GI hemorrhage were
      examined in which mean length of stay was 6.7 days. Colonoscopy was performed
      during 415 hospitalizations. Approximately a third of patients were discharged
      within 48 hours after colonoscopy. In the regression model, hemodynamic
      instability, higher comorbidity, performance of a tagged red blood cell nuclear
      scan, and surgery for hemostasis were significantly associated with a decreased
      likelihood of discharge. Having a colonoscopy was associated with an increased
      likelihood of being discharged compared with not having a colonoscopy at any
      given time point during hospitalization (hazard ratio 1.5: 95% CI[1.2, 1.8]. The
      mean lengths of stay for patients having colonoscopy within 24 hours of
      hospitalization was shorter than those having colonoscopy after 24 hours of
      hospitalization (5.4 vs. 7.2 days; p<0.008). CONCLUSIONS: In patients with lower
      GI hemorrhage, earlier colonoscopy predicted earlier hospital discharge. However,
      colonoscopy did not necessarily lead to expedited post-procedural discharge.
      Although early colonoscopy appears to shorten hospital length of stay,
      prospective studies of inpatient colonoscopy are needed to determine the impact
      of this approach on outcomes.

PMID- 14652551
TI  - Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter
      of Oddi function: a comparative pilot study in patients with idiopathic recurrent
      pancreatitis.
AB  - BACKGROUND: Sphincter of Oddi dysfunction plays an important etiologic role in
      idiopathic acute recurrent pancreatitis. Sphincter of Oddi manometry is the most
      accurate test of sphincter of Oddi function, but it is associated with an
      increased risk of post-procedure pancreatitis and is non-diagnostic in about a
      third of cases. Secretin MRCP has a diagnostic efficacy comparable to ERCP, but
      data on its sensitivity with regard to sphincter of Oddi function are lacking.
      The aim of this study was to compare secretin MRCP and pancreatic sphincter of
      Oddi manometry for evaluation of sphincter of Oddi function in patients with
      idiopathic acute recurrent pancreatitis. METHODS: Eighteen consecutive patients
      with idiopathic acute recurrent pancreatitis underwent secretin MRCP and
      pancreatic sphincter of Oddi manometry/ERCP. Data from 15 patients were suitable
      for analysis. Fifteen subjects with asymptomatic, non-pancreatic hyperamylasemia
      matched for age and gender underwent secretin MRCP and served as a control group.
      RESULTS: Sphincter of Oddi manometry documented sphincter dysfunction in 6/15
      patients (40%) and secretin MRCP, in 4/15 patients (26.7%). Sphincter of Oddi
      manometry confirmed the presence of elevated basal sphincter of Oddi pressure in
      two of the 4 patients with abnormal and other forms of sphincter of Oddi
      dyskinesia in the other two. None of the control subjects had an abnormal
      secretin MRCP. Secretin MRCP and sphincter of Oddi manometry were concordant in
      13/15 patients (86.7%); positive and negative diagnoses for sphincter of Oddi
      dysfunction agreed in, respectively, 81.8% and 100% (kappa value 0.706).
      CONCLUSIONS: Secretin MRCP seems to be a useful noninvasive procedure for
      investigation of pancreatic sphincter of Oddi function, but evaluation in larger
      series is needed.

PMID- 14652552
TI  - Prospective comparison of transcutaneous 3-dimensional US cholangiography,
      magnetic resonance cholangiography, and direct cholangiography in the evaluation
      of malignant biliary obstruction.
AB  - BACKGROUND: The purpose of this study was to investigate the ability of
      transcutaneous three-dimensional US cholangiography to depict the biliary tree in
      malignant obstruction, compared with that of MRCP and direct cholangiography.
      METHODS: Three-dimensional US and MRCP and direct cholangiography were performed
      in 40 patients with suspected malignant biliary obstruction. Diagnostic quality
      of the images, presence, level, and cause of ductal obstruction were assessed in
      a prospective, blinded fashion. The results were correlated with consensus
      interpretation (3 investigators), intra-operative findings, and histopathology or
      clinical follow-up. RESULTS: Three-dimensional US produced cholangiographic
      images of diagnostic quality. The appearance of these images was similar to that
      of MRCP or ERCP/percutaneous transhepatic cholangiography images. All modalities
      were highly sensitive in the detection of biliary dilatation. The accuracy of 3
      dimensional US, MRCP, and ERCP/percutaneous transhepatic cholangiography in
      determining the level of obstruction was, respectively, 92%, 95%, and 98%.
      Transcutaneous 3-dimensional US and MRCP accurately identified the cause of
      obstruction in, respectively, 90% and 95% of cases. Direct cholangiography
      revealed the correct diagnosis in 95% of the patients. CONCLUSIONS: Three
      dimensional US cholangiography is a new, noninvasive method with the capability
      to produce diagnostic cholangiograms. Three-dimensional US cholangiography may be
      used increasingly as an initial test to select patients who require further
      diagnostic evaluation by MRCP or therapeutic ERCP.

PMID- 14652553
TI  - Endoscopic findings and their clinical correlations in patients with symptoms
      after gastric bypass surgery.
AB  - BACKGROUND: The aim of this study was to describe the endoscopic findings in
      patients with upper GI symptoms after Roux-en-Y gastric bypass surgery and to
      correlate clinical features with endoscopic findings. METHODS: Patients with
      symptoms after Roux-en-Y gastric bypass referred for endoscopy were studied.
      Endoscopy was performed in standard fashion with a 9.8-mm diameter endoscope.
      RESULTS: Forty-nine patients underwent a total of 69 upper endoscopy procedures
      between January 2001 and February 2003. The most common endoscopic findings were
      the following: normal post-surgical anatomy (21 patients, 43%), marginal ulcer
      (13 patients, 27%), stomal stenosis (9 patients [19%], including 5 with a
      concomitant marginal ulcer), and staple-line dehiscence (8 patients [16%],
      including one with a marginal ulcer). Abdominal pain was the most common symptom
      (26 patients, 53%) and was more frequent among patients with a normal endoscopy
      compared with those with an abnormal endoscopy (p=0.04). Stomal stenosis was
      present in 39% of patients with nausea, vomiting, or dysphagia; it was not
      present in any patient without these symptoms (p=0.001). Fifteen percent of
      procedures performed within the first 6 postoperative months were normal,
      compared with 53% of those performed beyond 6 months (p=0.02). There was no
      complication of endoscopy. CONCLUSIONS: Among patients with symptoms after Roux
      en-Y gastric bypass presenting for endoscopy, normal post-surgical anatomy was
      the most common finding. Marginal ulcer was the most common abnormality.
      Presentation with abdominal pain and performance of endoscopy beyond the 6th post
      operative month were predictive of a normal endoscopy, and lack of nausea,
      vomiting, and dysphagia predicted the absence of stomal stenosis.

PMID- 14652554
TI  - Mucosal apposition in endoscopic suturing.
AB  - BACKGROUND: The proliferation of minimally invasive surgery has led to the
      development of numerous entirely intracorporeal endoscopic suturing techniques.
      These techniques allow for simple apposition of the GI mucosa. It is yet to be
      determined whether this results in long-term mucosal apposition. This study was
      designed to determine whether the current techniques of endoscopic suturing
      necessitate preliminary mucosal manipulation. METHODS: Seven dogs underwent
      laparotomy and gastrotomy to expose the proximal gastric mucosa. Three different
      suturing techniques were used to appose adjacent tissue folds: simple mucosal
      apposition, electrosurgical mucosal ablation before closure, and mucosal
      resection before closure. Apposition sites were scored histologically, based on
      tissue healing after 2 weeks. RESULTS: Mucosal ablation before tissue apposition
      resulted in significantly greater healing compared with simple apposition and
      resulted in histologic scoring similar to that for mucosal resection. The mean
      histologic score after ablation was 1.5, vs. 1.25 after mucosal resection, and
      0.9 for sites closed simply (p=0.02). CONCLUSIONS: Endoscopic suturing techniques
      may one day offer an alternative to surgical treatment in the management of
      numerous GI conditions. As this modality evolves, the incorporation of target
      tissue ablation or mucosal resection before tissue apposition requires
      consideration. Human studies evaluating the safety and long-term efficacy of
      these modifications are necessary.

PMID- 14652555
TI  - Endoscopic hemorrhoidal ligation of symptomatic internal hemorrhoids.
AB  - BACKGROUND: This study assessed the efficacy of endoscopic hemorrhoidal ligation
      for treatment of patients with symptoms caused by internal hemorrhoids. METHODS:
      A total of 576 consecutive patients with symptoms caused by internal hemorrhoids
      were enrolled in the study. Symptoms were rectal bleeding (239 patients) and
      prolapse (337 patients). The severity of the hemorrhoids was classified by using
      the grading system of Goligher. RESULTS: All patients were treated by the same
      operator. Mean follow-up was 17.5 months (range 8 to 24 months). The mean number
      of band ligations per session was 2.86. The mean number of treatment sessions was
      1.24. At least one grade reduction in the severity of the hemorrhoids was
      achieved in most patients (93.58%). Moreover, rectal bleeding was controlled in
      228 patients (95.4%), and rectal prolapse was reduced in 310 patients (91.99%).
      After treatment, 85 patients experienced anal pain, 37 had mild bleeding, 4
      developed external hemorrhoidal thrombosis, and one had a peri-anal abscess. The
      latter 5 patients were treated surgically and recovered uneventfully.
      CONCLUSIONS: Endoscopic hemorrhoidal ligation is a simple, safe, and effective
      treatment for patients with symptoms caused by internal hemorrhoids.

PMID- 14652556
TI  - Frequency of biliary crystals in patients with suspected sphincter of Oddi
      dysfunction.
AB  - BACKGROUND: The passage of gallstones (macro- or microlithiasis) is theorized to
      play a role in inducing sphincter of Oddi dysfunction. This study examined the
      frequency at which biliary crystals are found in patients with suspected type II
      and type III sphincter of Oddi dysfunction. METHODS: A total of 85 patients (66
      women, 19 men; mean age 38 years) with unexplained abdominal pain of suspected
      pancreatobiliary origin and no prior episode of pancreatitis underwent ERCP with
      sphincter of Oddi manometry and bile collection for crystal analysis. Eighty-one
      patients had a gallbladder in situ. No patient had evidence of stones or sludge
      on prior abdominal imaging. Sphincter of Oddi manometry was performed in standard
      retrograde fashion by using an aspirating catheter. Patients were classified by
      sphincter of Oddi dysfunction type by using a modified Hogan-Geenen
      classification system. Patients with type I sphincter of Oddi dysfunction were
      excluded. Bile was collected directly from the gallbladder (n=23) or common bile
      duct (n=62) after an infusion of 3.5 microg of cholecystokinin and was examined
      by light and polarizing microscopy for cholesterol crystals or calcium
      bilirubinate granules. RESULTS: The proportion of patients with crystals was 3.5%
      (3/85). Thirty-five patients (41%) had elevated biliary and/or pancreatic
      sphincter pressure (type II, 16; type III, 19), of whom one (3%) had cholesterol
      crystals. Fifty patients had normal sphincter pressure, of whom two (4%) had
      cholesterol crystals (p=0.6). All 3 patients with cholesterol crystals had a
      gallbladder in situ. Calcium bilirubinate granules were not found in any patient.
      CONCLUSIONS: Microlithiasis appears to be rare in patients suspected to have type
      II or type III sphincter of Oddi dysfunction. Evaluation of bile for crystals
      appears unproductive in this group of patients.

PMID- 14652557
TI  - Endoscopic management of occluded biliary Wallstents: a cancer center experience.
AB  - BACKGROUND: Biliary obstruction caused by unresectable malignancy commonly is
      treated by placement of a biliary self-expandable metallic stent. The endoscopic
      and percutaneous techniques for self-expandable metallic stent placement are well
      established and can be performed with a high success rate. Self-expandable
      metallic stent placement affords palliation of pruritus and enables treatment of
      advanced cancer with chemotherapeutic agents metabolized by the liver.
      Unfortunately, these stents tend to occlude with time. Optimal management of an
      occluded self-expandable metallic stent remains to be determined. METHODS: A
      retrospective review was undertaken to determine optimal management of the
      occluded self-expandable metallic stent. Patients with malignant biliary
      obstruction who had endoscopic management for occluded Wallstents that had been
      placed percutaneously and endoscopically were studied. All patients underwent
      ERCP with one of the following interventions: mechanical cleaning, insertion of a
      plastic stent within the Wallstent, or insertion of a second Wallstent. The
      effectiveness of the intervention and duration of stent patency thereafter was
      studied. RESULTS: A total of 34 patients with occluded biliary Wallstents
      underwent the following procedures: mechanical cleaning (6 patients), placement
      of a second Wallstent (4), or insertion of a plastic stent (24). Mechanical
      cleaning was effective in only one of 6 patients. For all 4 patients who
      underwent placement of a second Wallstent, there was resolution of jaundice or
      cholangitis and no reocclusion. Plastic stent insertion was successful in 22 of
      24 patients. Median duration of stent patency after intervention was 192 days
      (range 81-257 days) after second Wallstent placement, 90 days (11-393 days) after
      plastic stent insertion, and 21 days (3-263 days) after mechanical cleaning.
      Duration of stent patency was better when the initial malignant stricture
      involved the distal vs. the proximal bile duct. CONCLUSIONS: Occlusion of a
      biliary Wallstent is best managed by endoscopic insertion of a second Wallstent
      or a plastic stent. Mechanical cleaning is less effective. The level of the
      initial biliary obstruction influences stent patency.

PMID- 14652558
TI  - Familial adenomatous polyposis.

PMID- 14652559
TI  - Evidence-based medicine: what on earth does it have to do with endoscopy? and, is
      it the new "three-letter" word in endoscopic research?

PMID- 14652560
TI  - Endoscopic research in America (revisited).

PMID- 14652561
TI  - Gastric syphilis.

PMID- 14652562
TI  - Appendiceal mucocele.

PMID- 14652563
TI  - Schistosomal colonic polyposis.

PMID- 14652564
TI  - Spontaneous pancreaticorenal fistula.

PMID- 14652565
TI  - Volume (3-dimensional) space-time reconstruction of esophageal peristaltic
      contraction by using simultaneous US and manometry.
AB  - BACKGROUND: Conventional 3-dimensional endoluminal US was modified to evaluate
      peristaltic contractions in the esophagus. METHODS: Two-dimensional US images and
      simultaneous intraluminal pressures were acquired during peristaltic contractions
      by locating the transducer at fixed positions in the esophagus in 6 normal
      volunteers during swallowing. Three-dimensional images were reconstructed by
      using a computer-based 3-dimensional algorithm with time as the x axis. RESULTS:
      The peristaltic contraction sequence was viewed as a 3-dimensional US image. The
      geometric configuration of the esophagus, the muscle thickness, and corresponding
      pressures were evaluated. The 3-dimensional images demonstrate 4 phases of the
      peristaltic contraction sequence. CONCLUSIONS: Three-dimensional time-resolved
      reconstruction of endoluminal US images of the esophagus and simultaneous
      recording of manometric data allow visualization of geometric changes and
      correlation with pressure changes during peristaltic contraction. Four phases of
      the peristaltic contraction sequence are demonstrated clearly on the 3
      dimensional space-time images.

PMID- 14652566
TI  - EUS antegrade pancreatography with gastropancreatic duct stent placement: Review
      of two cases.
AB  - BACKGROUND: Endoscopic retrograde pancreatography is an established procedure for
      palliation of patients with pain caused by chronic pancreatitis associated with
      pancreatic ductal stricture. Some patients may not be candidates for endoscopic
      retrograde pancreatography because of surgically altered anatomy. Two cases are
      presented in which endoscopic retrograde pancreatography was unsuccessful and EUS
      guided antegrade pancreatography with gastropancreatic stent placement was
      performed. METHODS: EUS-guided antegrade pancreatography was performed in both
      patients by creating a gastropancreatic fistula through which dilation and stent
      placement were performed over a guidewire. RESULTS: Stent insertion was
      successful in both cases. Both patients experienced rapid improvement in
      symptoms. CONCLUSIONS: EUS-guided antegrade pancreatography with stent placement
      may be an alternative to endoscopic retrograde pancreatography when surgical
      reconstruction precludes access to the major and minor papillae.

PMID- 14652567
TI  - Open-biopsy-forceps technique for endoscopic removal of distally migrated and
      impacted biliary metallic stents.
AB  - BACKGROUND: Endoscopic removal of distally migrated and impacted biliary metallic
      stents is technically challenging. An open-biopsy-forceps technique for
      endoscopic removal of these migrated stents is described. METHODS: The technique
      was used in 4 patients with distally migrated and impacted covered metallic
      stents. A closed biopsy forceps was advanced through the stent mesh and opened
      within the stent to form an "anchor." With endoscope withdrawal, the stent was
      dislodged easily from the duodenum to the stomach. After grasping an end of the
      stent with a snare, the stent was removed by complete withdrawal of the
      endoscope. OBSERVATIONS: In all patients, the impacted stent was removed
      successfully. Mean time for removal was 10.2 minutes. Although ulceration was
      evident in the duodenal wall where the distal stent end was impacted in all
      patients, no other complication or adverse event was observed. CONCLUSIONS: The
      open-biopsy-forceps technique is useful for endoscopic removal of distally
      migrated and impacted biliary metallic stents.

PMID- 14652568
TI  - Endoscopic and histopathologic findings of Strongyloides stercoralis infection in
      a patient with AIDS.

PMID- 14652569
TI  - GI manifestations of mantle cell lymphoma.

PMID- 14652570
TI  - Diagnosis of ovarian cancer metastatic to the stomach by EUS-guided FNA.

PMID- 14652571
TI  - Capillary refilling sign demonstrated by capsule endoscopy.

PMID- 14652572
TI  - Obstructive duodenal lipoma successfully treated by endoscopic polypectomy.

PMID- 14652587
TI  - The many challenges of the self-care movement.

PMID- 14652588
TI  - Postoperative anticoagulation in vascular surgery--Part two: A summary of lessons
      learned in our successful discharge planning experience using enoxaparin after
      vascular surgery.
AB  - Postoperative anticoagulation is not an uncommon scenario for patients undergoing
      vascular procedures. Additional postoperative length of stay (LOS) is necessary
      to achieve a therapeutic international normalized ratio with traditional
      protocols using unfractionated heparin. In part one of this 2-part article, low
      molecular-weight heparin (LMWH), specifically enoxaparin, was shown to be a safe
      and effective alternative for anticoagulation after vascular surgical procedures.
      At the same time, its use can significantly reduce the average postoperative LOS
      after vascular procedures. This article describes a successful discharge planning
      experience using the LMWH enoxaparin after vascular procedures. We share our
      perspective on the role of the various members of the vascular surgical team as
      implemented in our acute care vascular surgical service clinical setting. Our
      discussion may offer ideas for consideration by vascular clinicians in their
      clinical settings.

PMID- 14652589
TI  - Carotid stents: is the gold standard ready for change?
AB  - Carotid artery stenting is emerging as an intervention for high-risk nonsurgical
      patients with high-grade symptomatic carotid artery stenosis. The purpose of this
      article is to inform advanced practice nurses about research findings related to
      carotid endarterectomy and carotid artery stenting. This overview of carotid
      angioplasty and stenting includes complications and guidelines for preprocedural,
      periprocedural, and postprocedural care. Standards of practice for managing
      carotid artery disease are highlighted with emphasis on primary and secondary
      prevention.

PMID- 14652591
TI  - The vascular nurse in practice: Results of prescribed exercise training in
      patients with intermittent claudication.
AB  - Intermittent claudication (IC) is a mild stage of peripheral arterial disease
      that affects between 3% and 7% of the population and up to 1 in 5 patients over
      the age of 75 years. Risk factors such as hypertension, hyperlipidemia, diabetes,
      smoking, and genetics increase the incidence of peripheral arterial disease.
      Patients with IC have limitations in functional capacity and can benefit from
      regular exercise. Walking is the preferred mode of exercise and improves the
      symptoms of claudication in several ways. Vascular nurses can play an important
      role during exercise therapy. A personalized, home-based exercise program can be
      developed, and nurses can assist and motivate patients during follow-up periods.
      Helping patients to quit smoking and control other risk-factor modifications (ie,
      high blood pressure and lipid levels) also has high priority in daily practice of
      the vascular nurse. This prospective study will illustrate the results of
      prescribed home-based exercise training by a vascular nurse on the maximum
      painless walking distance for patients with IC and will be applied to subgroups
      of vascular pathology.

PMID- 14652592
TI  - Standards of vascular nursing practice.

PMID- 14652593
TI  - Geriatric best practices in nursing: optimizing functional independence.

PMID- 14652594
TI  - "Secrets" for managing your paperwork.

PMID- 14652596
TI  - Carotid artery aneurysm.

PMID- 14652598
TI  - Strain rate acceleration yields a better index for evaluating left ventricular
      contractile function as compared with tissue velocity acceleration during
      isovolumic contraction time: an in vivo study.
AB  - OBJECTIVE: Our study aimed to investigate whether strain rate acceleration (SRA)
      during isovolumic contraction time (IVCT) could serve as a sensitive indicator of
      myocardial function. METHODS: A total of 8 sheep underwent occlusion of left
      anterior descending coronary artery or diagonal branches and 2 sheep underwent
      left circumflex coronary artery occlusion to create septal, apical, or basal
      segment myocardial ischemia 19 to 27 weeks before the study. Baseline, volume
      loading, dobutamine, and metoprolol infusion were used to produce 4 hemodynamic
      stages for each sheep. Doppler tissue imaging was acquired using a 5-MHz probe
      (GE/VingMed Vivid Five, GE Medical Systems, Milwaukee, Wis) on open-chest animals
      using the liver as a standoff at the apex. Using software (EchoPac, GE Medical
      Systems), SRA during IVCT was calculated and compared with tissue velocity
      acceleration (TVA) during IVCT from areas located in the normal and ischemic
      zones. Also, invasively monitored left ventricle dP/dt was measured as reference
      contractile function. RESULTS: Both TVA and SRA during IVCT showed higher values
      for normal tissue than for ischemic area (P <.0001). SRA for normal wall segments
      changed significantly during the 4 stages (P =.01) with corresponding changes on
      high-fidelity left ventricular pressure catheters (r = 0.92). TVA over normal
      segments showed no significant change (P =.29) in the 4 hemodynamic stages. Both
      TVA and SRA of the ischemic segments showed no significant change with
      pharmacologic maneuvers or loading conditions. CONCLUSIONS: SRA and TVA during
      IVCT are both useful indicators for detecting abnormal heart wall motion.
      However, SRA tends to be more sensitive than TVA for differentiating the response
      to stress conditions.

PMID- 14652599
TI  - Clinical relevancy of the myocardial velocity gradient: limitations of a binary
      response.
AB  - BACKGROUND: Doppler tissue echocardiographic myocardial velocity gradient (MVG)
      overcomes translational or tethered motion effects. Diagnostic applications rely
      on MVG numeric value, an instantaneous value calculated at peak endocardial
      velocity. Our aim was to test the clinical relevancy of MVG for patients with
      dilated cardiomyopathy (CM) at rest. Efficiency of MVG, as a marker of the
      underlying mechanism, ischemic or nonischemic, was compared with that of mean
      velocities averaged over a cycle. METHODS: Peak and mean velocities were measured
      and MVG calculated during ejection, and early and late diastole, in the
      endocardium and epicardium on color M-mode Doppler tissue echocardiographic
      parasternal recordings of the posterior wall, simultaneously imaged with the
      septum. The population consisted of 34 patients with similar clinical
      presentation (left ventricular ejection fraction < 40%, left ventricular end
      diastolic diameter > 6 cm, and proven ischemic [14] or nonischemic [20] dilated
      CM) and 16 control subjects. RESULTS: Doppler tissue echocardiography data
      significantly differed between control subjects and all patients with CM. Between
      patients, the only significant differences were found at the posterior wall for
      mean velocities at the epicardium in systole (9 +/- 4 mm/s for ischemic vs 14 +/-
      5 mm/s for nonischemic, P =.002), and at both layers in early diastole
      (endocardium, 14 +/- 9 vs 29 +/- 12 mm/s, P =.0004; epicardium, 12 +/- 4 vs 22 +/
      11 mm/s, P =.002; ischemic vs nonischemic CM, respectively). CONCLUSION:
      Specific features of CM were characterized by myocardial velocity changes studied
      layer by layer throughout a phase. The binary response of transient peak MVG
      could not reach this goal.

PMID- 14652600
TI  - The role of apically directed intraventricular isovolumic relaxation flow in
      speeding early diastolic left ventricular filling.
AB  - Left ventricular (LV) systolic performance has been acknowledged to have a close
      relation to LV early diastolic filling and LV relaxation. However, the mechanism
      showing how good LV systolic function enhances the LV early diastolic filling has
      not been fully elucidated from the viewpoint of intraventricular flow dynamics.
      Thus, we investigated this issue in 82 patients with suggested coronary artery
      disease who underwent cardiac catheterization. Apically directed intraventricular
      isovolumic relaxation flow (IRF) and the propagation velocity of early diastolic
      filling flow were measured using pulsed and color Doppler echocardiography. LV
      ejection fraction and LV relaxation time constant tau were obtained in cardiac
      catheterization. As we were not able to measure the IRF velocity less than 14
      cm/s that was limited by a Doppler low-cut filter, we analyzed the data collected
      from 78 patients with measurable IRF velocity. The IRF velocity significantly
      correlated with LV ejection fraction (r = 0.74, P <.001) and with LV relaxation
      time constant tau (r = -0.31, P <.01). The propagation velocity of early
      diastolic filling flow significantly correlated with the IRF velocity (r = 0.73,
      P <.001) and also significantly correlated with LV ejection fraction (r = 0.70, P
      <.001). Good LV systolic performance augments LV early diastolic filling
      directly, mediated by IRF. A faster IRF velocity may play a role in delivering
      good LV systolic performance to LV early diastolic filling.

PMID- 14652601
TI  - Noninvasive differentiation of pseudonormal/restrictive from normal mitral flow
      by Tei index: a simultaneous echocardiography-catheterization study in patients
      with acute anteroseptal myocardial infarction.
AB  - BACKGROUND: Differentiation of pseudonormal/restrictive from normal mitral flow
      is still clinically problematic. Pseudonormal/restrictive flow is usually
      associated with left ventricular dysfunction, which can be detected by Doppler
      Tei index, combining systolic and diastolic function. Therefore, the purpose of
      this study was to test the feasibility of the Tei index to differentiate
      pseudonormal/restrictive from normal mitral flow. METHODS: In 26 patients with
      anteroseptal acute myocardial infarction and early diastolic mitral flow velocity
      (E) to late diastolic mitral flow velocity (A) ratio (E/A) > or = 1, left
      ventricular volumes; E and A; deceleration time of E; and the Tei index, defined
      as the sum of the isovolumic contraction and relaxation time divided by ejection
      time, were evaluated by Doppler echocardiography, and pulmonary capillary wedge
      pressure was measured by catheterization. Pseudonormal/restrictive mitral flow
      was defined as E/A > or = 1 associated with pulmonary capillary wedge pressure >
      12 mm Hg. RESULTS: There were 19 and 7 patients with pseudonormal/restrictive and
      normal mitral flow, respectively. Among the indices of left ventricular function,
      the Tei index achieved the best correlation with pulmonary capillary wedge
      pressure (r(2) = 0.66, P <.0001). By setting the Tei index > or = 0.55 as the
      criteria for pseudonormal/restrictive mitral flow, this diagnosis had the
      sensitivity, specificity, and accuracy of 84%, 100%, and 88%, respectively.
      CONCLUSION: The Tei index allows noninvasive differentiation of
      pseudonormal/restrictive from normal mitral flow.

PMID- 14652602
TI  - Rapid and accurate noninvasive assessment of global left ventricular systolic
      function using biplane advanced automated contour tracking method.
AB  - BACKGROUND: The advanced automated contour tracking (AACT) method has been newly
      developed for automated detection of the left ventricular endocardial boundary.
      Left ventricular ejection fraction (LVEF) may be estimated by applying the AACT
      method to 2 orthogonal planes of patients even when regional wall-motion
      abnormalities exist. The purpose of this study was to examine the reliability of
      the biplane AACT method in the measurement of LVEF in patients with suggested
      ischemic heart disease with use of quantitative gated single photon emission
      computed tomography (QGS) as a reference standard. METHODS: The study population
      consisted of 47 consecutive patients with suggested ischemic heart disease. All
      patients underwent 2-dimensional echocardiography and QGS. Biplane LVEF from
      apical 4- and 2-chamber views was measured offline by the AACT method using disk
      summation method. The accuracy of the AACT method for LVEF measurement was
      determined in comparison with QGS. RESULTS: In 41 (29 with and 12 without
      regional wall-motion abnormalities) of 47 patients (87%), automated tracing of
      the endocardial border was adequately achieved with the AACT method. LVEF
      measured by the AACT method correlated well with that measured by QGS (y = 0.97x
      +2.4, r = 0.91). The mean difference between AACT and QGS was 0.6 +/- 5.5% (mean
      +/- SD). The mean time required for analysis of 1 set of images during 1 cardiac
      cycle by the AACT method was much shorter than that required by manual tracing
      method (7 +/- 1 vs 37 +/- 4 seconds, P <.0001). CONCLUSION: The biplane AACT
      method provides accurate and quick measurement of LVEF in patients even with
      regional wall-motion abnormalities.

PMID- 14652604
TI  - Noninvasive assessment of myocardial ischemia in the left ventricular inferior
      regions by coronary flow reserve measurement using transthoracic Doppler
      echocardiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the potential of noninvasive
      measurement of coronary flow reserve (CFR) by transthoracic Doppler
      echocardiography (TTDE) for the assessment of myocardial ischemia in the left
      ventricular (LV) inferior regions. BACKGROUND: Although coronary flow assessment
      by TTDE has been determined for the assessment of perfusion abnormality in the LV
      anterior regions, the usefulness of this method has not been well investigated in
      the LV inferior regions. METHODS: We studied 50 patients (43 men; mean age 60 +/-
      9 years) with suggested coronary artery disease. CFR in the posterodescending
      coronary artery (PDA) was calculated as a ratio of hyperemic to basal peak (peak
      CFR) and mean (mean CFR) flow velocities in the PDA, which were measured by TTDE.
      CFR values were compared with the results of exercise 201-thallium single photon
      emission computed tomography. RESULTS: CFR was successfully measured in 43 of 50
      patients (86%). Mean and peak CFR < 2 were shown in 10 of 12 patients with
      abnormal perfusion in the LV inferior regions, whereas CFR > or = 2 were shown in
      30 of 31 patients with normal perfusion. Thus, CFR < 2 in the PDA by TTDE had a
      sensitivity of 83% and a specificity of 97% for the assessment of perfusion
      abnormality in the LV inferior regions by 201-thallium single photon emission
      computed tomography. CONCLUSIONS: CFR in the PDA measured by TTDE provides data
      equivalent to those obtained by 201-thallium single photon emission computed
      tomography for myocardial ischemia in the LV inferior regions.

PMID- 14652603
TI  - Normal values of left ventricular systolic and diastolic function derived from
      signal-averaged acoustic quantification waveforms: a multicenter study.
AB  - Automated border-detection techniques such as acoustic quantification have proven
      accurate and useful for quantifying left ventricular (LV) function. We acquired
      LV acoustic quantification waveforms from the parasternal short-axis window in
      140 healthy patients in the age range of 16 to 78 years. Signal-averaged
      waveforms were analyzed for parameters of systolic and diastolic performance. The
      average fractional area change was 54 +/- 12%, and there were no significant
      changes in LV systolic function in the age range studied. There were significant
      changes in diastolic parameters with aging. The percentage of contribution to
      total LV filling occurring during atrial filling nearly tripled during the 6
      decades studied, from 13% in the youngest cohort to 36% in the eighth decade of
      life. This study provides normal reference values for systolic and diastolic
      parameters of LV function determined from signal-averaged acoustic quantification
      waveforms acquired from the parasternal short-axis view in adult and adolescent
      patients over a wide age range.

PMID- 14652605
TI  - Simultaneous real-time echocardiographic imaging of myocardial perfusion and
      regional function using color-encoded, contrast-enhanced power modulation.
AB  - We hypothesized that color-encoded, contrast-enhanced, power modulation imaging
      could allow simultaneous quantification of myocardial perfusion and regional left
      ventricular function. We studied 12 anesthetized, closed-chest pigs at baseline,
      during acute ischemia, and during reperfusion, and 8 patients after acute
      myocardial infarction. Color kinesis was used to color encode endocardial motion
      during real-time contrast perfusion imaging with high-energy ultrasound pulses.
      Wall motion was assessed by calculating regional fractional area changes.
      Translation-free perfusion analysis was performed in automatically identified
      myocardial regions of interest. Steady-state intensity and postimpulse rate of
      contrast replenishment were calculated. In all animals, ischemia caused
      reversible changes in the images and the perfusion- and function-calculated
      indices. A significant decrease in pixel intensity (14%) and contrast
      replenishment rate (66%) in left anterior descending coronary artery segments, in
      agreement with fluorescent microspheres measurements, coincided with a decrease
      in fractional area change (34%). For patients, respective perfusion and function
      indices were 61%, 51%, and 58% lower in segments where perfusion defects,
      regional wall-motion abnormalities, or both were noted in gray scale images.
      Color-encoded, contrast-enhanced power modulation allows simultaneous real-time
      imaging and quantitative analysis of myocardial perfusion and regional left
      ventricular function.

PMID- 14652606
TI  - Measurement of radial artery contrast intensity to assess cardiac microbubble
      behavior.
AB  - OBJECTIVES: We sought to determine whether analysis of the contrast signal from
      the radial artery is better able to reflect changes in left ventricular (LV)
      microbubble dynamics than the signal from the LV itself. BACKGROUND: Assessment
      of microbubble behavior from images of the LV may be affected by attenuation from
      overlying microbubbles and nonuniform background signal intensities. The signal
      intensity from contrast in a peripheral artery is not affected by these artifacts
      and may, thus, be more accurate. METHODS: After injection of a contrast bolus
      into a peripheral vein, signal intensity was followed simultaneously in the LV
      and radial artery. The measurements were repeated using continuous, triggered,
      low and high mechanical index harmonic imaging of the LV. RESULTS: Peak and
      integrated signal intensities ranged from 25 dB and 1550 dB/s, respectively, with
      radial artery imaging to 5.6 dB and 471 dB/s with ventricular imaging. Although
      differences in microbubble behavior during the different imaging protocols could
      be determined from both the LV and radial artery curves, analysis of the radial
      artery curves yielded more consistent and robust differences. CONCLUSIONS: The
      signal from microbubbles in the radial artery is not affected by shadowing and
      is, thus, a more accurate reflection of microbubble behavior in the LV than the
      signal from the LV itself. This may have important implications for the
      measurement of myocardial perfusion by contrast echocardiography.

PMID- 14652607
TI  - Two-dimensional and Doppler transesophageal echocardiographic delineation and
      flow characterization of anomalous coronary arteries in adults.
AB  - OBJECTIVES: The purpose of this study was to examine the use of transesophageal
      echocardiography (TEE) in the identification and flow characterization of
      congenital coronary anomalies. BACKGROUND: Congenital coronary anomalies in
      adults are rare but may cause serious cardiac complications. The use of TEE in
      evaluation of this entity has not been well defined. Very little is known
      regarding flow patterns in anomalous coronaries assessed by Doppler TEE. METHODS:
      A total of 32 consecutive adult patients were studied using TEE to define the
      origin, course, and proximal flow pattern of suspected coronary anomalies.
      RESULTS: Coronary anomalies identified using TEE included anomalous origin from
      the pulmonary trunk (n = 2), right sinus (n = 18), left sinus (n = 9), single
      coronary (n = 2), and left main coronary fistula (n = 1). Multiplane TEE
      performed in 20 cases simplified the delineation of more complex coronary
      anomalies. The origin was identified in all patients, proximal course delineated
      in 31, and proximal flow pattern characterized by pulsed Doppler in 23 of 32
      patients. In 16 anomalous left main, left anterior descending, or left circumflex
      coronary arteries, an abnormal systolic flow pattern (ie, systolic/diastolic time
      velocity integral ratio >1) occurred exclusively (P <.001) when the anomalous
      artery had an intermediate (100%; 5/5) versus anterior or posterior course (0%;
      0/11) relative to the aortic and pulmonary artery trunks. A systolic flow pattern
      was also evident in 4 (80%) of 5 patients with an anomalous right coronary artery
      with an intermediate course. CONCLUSIONS: TEE, particularly with a multiplane
      probe, has an important complementary role to coronary angiography in delineating
      the proximal course and pattern of flow in anomalous coronaries. Predominant
      systolic flow pattern in anatomically left proximal anomalous coronaries
      signifies an intermediate course between the aorta and the pulmonary trunk and
      may be clinically useful for risk stratification.

PMID- 14652608
TI  - Cost-effectiveness analysis of noninvasive strategies to evaluate patients with
      chest pain.
AB  - We evaluated clinical and economic outcomes of diagnostic strategies on the basis
      of pharmacologic stress echocardiography (PhSE) versus exercise
      electrocardiography test (EET) in 527 patients with chest pain (274 women; age 59
      +/- 10 years) who underwent both EET and PhSE. We investigated 3 strategies, ie,
      coronary angiography: after positive EET (strategy 1); after positive PhSE
      (strategy 2); or after a positive PhSE performed after a positive EET (strategy
      3). A patient was correctly identified if he or she had negative test results and
      no events, or had positive test results and abnormal coronaries. The cost per
      patient correctly identified was calculated as the ratio between the cost of each
      strategy and the number of patients correctly identified. The accuracy in
      correctly identifying the patients was 78%, 92%, and 91% with strategies 1, 2,
      and 3, respectively. The cost of each patient correctly identified was 1572 US
      dollars, 1097 US dollars, and 1081 US dollars with strategies 1, 2, and 3,
      respectively. In conclusion, PhSE-based strategies are cost-effective versus EET.

PMID- 14652609
TI  - Accuracy of mitral valve area measurements using transthoracic rapid freehand 3
      dimensional scanning: comparison with noninvasive and invasive methods.
AB  - OBJECTIVE: The feasibility and accuracy of direct transthoracic 3-dimensional
      (3D) mitral valve area (MVA) measurements obtained using freehand scanning was
      investigated in patients with mitral stenosis. METHODS: A total of 30 patients
      (26 women, 4 men; aged 55 +/- 13 years) underwent a 2-dimensional (2D) and
      Doppler study 1 hour before percutaneous balloon mitral valvuloplasty.
      Transthoracic freehand data were acquired using a magnetic receiver attached to a
      broadband transducer, gated to electrocardiography and respiration. Volumetric
      MVA measurements from the left ventricle and left atrium were obtained and
      compared with MVA measurements derived from 2D planimetry, pressure half-time,
      and proximal isovelocity surface area. Invasive Gorlin MVA measurements were the
      gold standard for comparison. RESULTS: In all, 29 patients (97%) had 3D data
      allowing MVA measurements. Direct 3D measurements from the left ventricle had the
      least bias (0.06 +/- 0.19 cm(2)) and tightest limits of agreement (-0.44 to 0.32)
      compared with left atrium measurements (0.17 +/- 0.25 cm(2) and -0.67 to 0.33,
      respectively). The proximal isovelocity surface area method (bias: 0.09 +/- 0.34
      cm(2)) was the most accurate of all 2D methods followed by pressure half-time
      (0.17 +/- 0.36 cm(2)) and planimetry (0.21 +/- 0.29 cm(2)). CONCLUSION: Direct 3D
      MVA measurements from the left ventricle using transthoracic freehand scanning
      are more accurate than traditional 2D methods.

PMID- 14652610
TI  - Leaflet concavity: a rapid visual clue to the presence and mechanism of
      functional mitral regurgitation.
AB  - Repairing mitral regurgitation (MR) requires an understanding of its mechanism.
      Evaluating restricted leaflet closure in functional MR is challenging. Tenting
      area between leaflets and annulus in long-axis (LAX) views correlates with MR,
      but is positive even in control subjects; in the 4-chamber view, the incomplete
      mitral leaflet closure (IMLC) tenting pattern may be subtle and variable. We
      tested the hypothesis that leaflet concavity toward the left atrium in the LAX
      view, a rapid visual clue indicating abnormal tethering predominantly by
      intermediate chords, is a strong indicator of functional MR. We reviewed 90
      patients: 40 with inferior myocardial infarction and ejection fraction > or =
      50%; 40 with global left ventricular dysfunction and ejection fraction < 50%; and
      10 control subjects. We assessed leaflet shape (concave or convex toward the left
      atrium) and maximum systolic proximal MR jet width in the LAX views. To quantify
      shape, we measured the leaflet concavity area between the anterior leaflet and a
      line connecting its ends. Conventional IMLC area was also assessed. Patients with
      leaflet concavity had significantly greater MR than those without this finding
      (jet width of 4.6 +/- 0.7 vs 0.5 +/- 0.1 mm, P <.0001), indicating mild-moderate
      versus trace MR, with differences comparable in those with inferior myocardial
      infarction and left ventricular dysfunction. Leaflet concavity area most strongly
      predicted MR by multivariate regression (R(2) = 0.7). Conventional IMLC area did
      not uniquely distinguish patients with or without MR and correlated more weakly
      with MR (R(2) = 0.30 vs 0.73). Mitral leaflet concavity in the LAX view provides
      rapid and reliable recognition of functional MR, with greater reliability than
      IMLC area. This shape, consistent with tethering by intermediate chords, may have
      implications for potential intervention.

PMID- 14652611
TI  - An alternative to standard continuity equation for the calculation of aortic
      valve area by echocardiography.
AB  - Calculation of aortic valve area by echocardiography is sometimes technically
      difficult. We tested a modified continuity equation to help measure valve area in
      those difficult cases. The studies of 105 patients with aortic stenosis were
      analyzed retrospectively. We calculated aortic valve area by standard continuity
      equation and by the modified method where Doppler-derived stroke volume was
      replaced by the difference between diastolic and systolic volume according to
      Simpson's biplane method of disks. The correlation between the 2 methods was
      excellent. For patients with left ventricular outflow tract acceleration,
      modified continuity equation correlated better than standard continuity equation
      with invasively measured aortic valve area by Gorlin equation. We conclude that
      the modified method is accurate and becomes an attractive alternative to the
      conventional continuity equation especially for patients in whom stroke volume
      calculation by Doppler may be unreliable for technical reasons.

PMID- 14652612
TI  - Use of an echocardiographic contrast agent to establish safety of cardioversion
      in a patient with a ligated left atrial appendage.
AB  - Transesophageal echocardiographic-guided cardioversion is a safe, accepted
      technique to minimize risk of stroke and embolic events when electrically
      converting atrial fibrillation to normal sinus rhythm. The presence of thrombus
      in the left atrial appendage (LAA) is a contraindication to performing
      cardioversion in these patients. For patients with a surgically ligated LAA,
      thrombus may be more prevalent and may still represent an embolic risk because of
      incomplete closure of the LAA. We report use of an echocardiographic contrast
      agent in a patient with a thrombus in a ligated LAA to determine safety of
      cardioversion.

PMID- 14652613
TI  - Subepicardial aneurysm of the left ventricle.
AB  - Three patients are presented in whom a subepicardial aneurysm developed as a
      complication of a myocardial infarction. This aneurysm of the left ventricle is
      unusual and has 3 distinctive traits: an abrupt interruption of the myocardium
      that comprises the mouth and typically a narrow neck of the aneurysm; aneurysmal
      wall comprised of epicardium with or without a thin myocardial layer; and a
      propensity to rupture spontaneously regardless of the wall components or stage of
      development. All 3 patients were given a diagnosis using echocardiography and
      underwent immediate surgical aneurysmectomy. One patient died as a result of
      renal and respiratory failure postoperatively. The long-term outcome of the other
      2 patients was favorable without evidence of additional cardiac rupture or
      instability.

PMID- 14652614
TI  - Successful surgical repair of a giant left main coronary artery aneurysm with
      arteriovenous fistula draining into a persistent left superior vena cava and
      coronary sinus: role of intraoperative transesophageal echocardiography.
AB  - We report the case of a 74-year-old woman with a history of hypertension,
      hypercholesterolemia, and pacemaker who presented to the hospital with new onset
      New York Heart Association class IV congestive heart failure. Transthoracic
      echocardiography revealed a markedly dilated right ventricle with normal right
      ventricular systolic function. There was moderate pulmonary hypertension with an
      estimated pulmonary artery systolic pressure of 60 mm Hg. Her echocardiogram 1
      year earlier had demonstrated normal right ventricular size and systolic
      function, and no pulmonary hypertension. Additional transthoracic imaging with
      saline contrast study through a left peripheral vein demonstrated the presence of
      a dilated coronary sinus with a persistent left superior vena cava. Color Doppler
      demonstrated turbulent flow within the coronary sinus with evidence of
      significant left-to-right shunting. Cardiac catheterization revealed a massively
      dilated left main coronary artery aneurysm with an arteriovenous fistula into the
      left superior vena cava and coronary sinus. The calculated Qp/Qs was 2:1. The
      patient underwent 2 unsuccessful attempts at percutaneous intervention to occlude
      the arteriovenous fistula. She then underwent successful surgical closure of the
      coronary arteriovenous fistula. The important role of intraoperative
      transesophageal echocardiography in guiding this technically challenging surgical
      case is discussed.

PMID- 14652615
TI  - Myocardial involvement in a patient with Burkitt's lymphoma mimicking
      hypertrophic cardiomyopathy.
AB  - Burkitt's lymphoma is a highly aggressive type of non-Hodgkin's lymphoma
      frequently associated with extranodal or abdominal manifestations. We report the
      case of a young woman with generalized Burkitt's lymphoma, initially presenting
      with signs and symptoms of central nervous system involvement. Myocardial
      infiltration mimicking hypertrophic cardiomyopathy was detected with
      electrocardiogram, echocardiography, magnetic resonance imaging, and positron
      emission tomographic scintigraphy with F-18 desoxy-glucose. These abnormalities
      resolved after high-intensity chemotherapy with a modified B-cell acute
      lymphoblastic leukemia (B-ALL) protocol.

PMID- 14652616
TI  - Cardiac angiosarcoma: an unusual presentation simulating mitral stenosis and
      constrictive-effusive pericarditis.
AB  - This case report details a patient with a cardiac angiosarcoma who had an unusual
      presentation with hemodynamics consistent with mitral stenosis and constrictive
      effusive pericarditis. It illustrates how transesophageal echocardiography adds
      to the information obtained from transthoracic imaging and hemodynamics in this
      unusual presentation of a cardiac tumor.

PMID- 14652617
TI  - Clinical applications of strain rate imaging.
AB  - Myocardial strain (epsilon) is a dimensionless index of change in myocardial
      length in response to an applied force. epsilon Rate (SR) is the rate of change
      of length and is usually obtained as the time derivative of the epsilon signal.
      In echocardiography, SR is calculated as the difference between 2 velocities
      normalized to the distance between the 2 velocities. SR imaging (SRI) has a
      theoretic advantage over Doppler tissue imaging in that SRI is relatively immune
      to cardiac translational motion and tethering. Therefore, SRI may be superior to
      Doppler tissue imaging in quantitative assessment of regional myocardial function
      and may find clinical application in the interrogation of coronary artery
      disease. The high frame rates of SRI have also renewed interest in timings of
      global and regional mechanical events, and their potential clinical applications.
      The high temporal resolution allows SRI to depict regional systolic and diastolic
      asynchrony. Ongoing clinical trials will determine the sensitivity, specificity,
      and accuracy of SRI parameters for a variety of clinical conditions. Potential
      clinical applications include investigation of ischemia (at rest and with
      stress), myocardial viability, and altered global and regional systolic and
      diastolic function in cardiomyopathies. Suboptimal signal quality remains a major
      limitation of strain imaging, and advances in data acquisition and postprocessing
      capabilities will help determine its future incorporation into standard regional
      myocardial assessment.

PMID- 14652618
TI  - Extent of overweight among US children and adolescents from 1971 to 2000.
AB  - CONTEXT: The prevalence of overweight (OW) among children in the United States
      has increased during the last three decades, but prevalence measures fail to
      reveal the extent to which OW children exceed the OW threshold. OBJECTIVE: To
      measure the amount by which OW children exceed the OW threshold. To examine the
      trend in this measure over the last three decades using data with measured
      weights and heights. DESIGN, SETTING AND PARTICIPANTS: Data used for analysis are
      from the National Health and Nutrition Examination Survey (NHANES) for persons
      between 2 and 19 y of age from 1971 to 2000. Anthropometric measures were
      obtained by trained health technicians, and the sample sizes range from 4037 in
      1999-2000 to 10,590 in 1988-1994. MAIN OUTCOME MEASURE: The extent of OW is
      measured as the average amount by which each child's body mass index (BMI)
      exceeds their age and gender-specific OW threshold. This measure is examined by
      sex, age group and race/ethnicity. The OW threshold for those aged 2-19 y is
      defined as at or above the 95th percentile of the sex-specific BMI for age growth
      charts. RESULTS: The extent of child OW has been increasing faster than the
      prevalence of child OW for all classifications considered in this paper,
      including the analysis by age, sex, race and ethnicity. The prevalence of OW for
      children aged 2-19 y increased by 182% between 1971-1974 and 1999-2000, while the
      extent of OW increased by 247% over the same time period. CONCLUSIONS: Unlike
      prevalence measures, the measure of the extent of child OW is sensitive to
      changes in the BMI distribution of the overweight. This analysis reveals that not
      only have more children become OW in the last three decades, but OW children have
      been getting heavier.

PMID- 14652619
TI  - Correlation between BMI, leisure habits and motor abilities in childhood (CHILT
      project).
AB  - INTRODUCTION: The prevalence of childhood obesity is increasing with its negative
      medical and psychosocial consequences. This paper examines the association
      between body mass index (BMI), motor abilities and leisure habits of 668 children
      within the CHILT (Children's Health InterventionaL Trial) project. METHOD: A
      total of 668 children (51.0% boys; 49.0% girls) and their parents were questioned
      on sport and leisure behaviour of the children. The anthropometric data were
      measured. Motor abilities were determined by a body gross motor development test
      for children (Koperkoordinationstest fur Kinder; KTK) and a 6-min run. RESULTS:
      The children were 6.70 +/- 0.42 y old, 122.72 +/- 5.36 cm tall and weighed 24.47
      +/- 4.59 kg, the average BMI was 16.17 +/- 2.27 kg/m2. KTK showed an average
      motor quotient (MQ) of 93.49 +/- 15.01, the 6-min run an average of 835.24 +/-
      110.87 m. Both tests were inversely correlated with BMI (KTK and BMI r=-0.164
      (P<0.001); 6-min run and BMI r=-0.201 (P<0.001)); the group of overweight/obese
      children showed poorer results than the normal/underweight ones, even after
      adjustment for gender and age (in each case P<0.001). Children with the greatest
      extent of exercise achieve the highest MQ (P=0.035). SUMMARY: Overweight/obesity
      is associated with a poorer body gross motor development and endurance
      performance. On the other hand, an active lifestyle is positively correlated with
      a better gross motor development in first-grade children. Therefore, to prevent
      the negative consequences of physical inactivity and overweight/obesity early
      intervention to support exercise and movement is recommended.

PMID- 14652620
TI  - Ethnic differences in the relationship between fasting leptin and BMI in
      children.
AB  - OBJECTIVE: To compare the relationship between fasting serum leptin levels and
      body mass index (BMI) in children from different ethnic groups. SUBJECTS:
      Children aged 6-10 y from rural Gambia (n=471) and central Italy (n=839).
      MEASUREMENTS: Anthropometry (z-score of BMI) and fasting serum leptin
      concentrations. RESULTS: The Italian children had significantly higher mean BMI z
      scores than the Gambian children (males: Italy 1.58, Gambia -1.44, P< or =0.0001;
      females: Italy 1.33, Gambia -1.42, P< or =0.0001) and significantly higher serum
      leptin concentrations (males: Italy 8.86 ng ml(-1), Gambia 1.78 ng ml(-1), P< or
      =0.0001; females: Italy 11.31 ng ml(-1), Gambia 2.22 ng ml(-1), P< or =0.0001). A
      significantly different relationship was observed between z-score of BMI and
      serum leptin levels in the Gambian and the Italian children for both boys and
      girls. CONCLUSION: A different relationship exists between z-score of BMI and
      leptin levels in these two groups of children from very diverse ethnic
      backgrounds. Future studies using detailed measures of body composition and
      energy balance are needed to help understand this relationship.

PMID- 14652621
TI  - Inter-relationships among childhood BMI, childhood height, and adult obesity: the
      Bogalusa Heart Study.
AB  - OBJECTIVE: Although the body mass index (BMI, mass index, kg/m2) is widely used
      as a surrogate measure of adiposity, it is moderately associated (r approximately
      0.3) with height among children. We examined whether the resulting preferential
      classification of taller children as overweight is appropriate. DESIGN: Cross
      sectional analyses of children (ages, 3-17 y) examined the relation of height to
      adiposity (as assessed by BMI and skinfold thicknesses) and fasting levels of
      insulin. Longitudinal analyses examined the relation of childhood height and
      weight-height indices to adult (mean age, 25 y) levels of adiposity and fasting
      insulin. SUBJECTS: Children (n=11,406) and adults (n=2911) who had participated
      in the Bogalusa Heart Study. MEASUREMENTS: We constructed three weight-height
      indices: BMI, W/H3, and W/Hp. The triceps and subscapular skinfolds, as well as
      fasting levels of insulin, were also measured. RESULTS: The classification of
      children as overweight (BMI-for-age > or =95th percentile) varied markedly by
      height, with a 10-fold difference in the prevalence of overweight across
      quintiles of height between the ages of 3 and 10 y. Childhood height, however,
      was also related to skinfold thicknesses and insulin levels, and all associations
      were modified in a similar manner by age. Furthermore, childhood height was
      related to adult adiposity, and of the three childhood weight-height indices, BMI
      showed the strongest associations with adult adiposity. CONCLUSIONS: Because BMI
      reflects the positive association between height and adiposity among children, it
      is a better weight-height index than is either W/H3 or W/Hp.

PMID- 14652623
TI  - Potency assessment of the new generation of coagulation factor concentrates--time
      for a new paradigm?

PMID- 14652624
TI  - Do platelets trigger atherosclerosis?

PMID- 14652625
TI  - Atrial fibrillation, thromboembolism, and haemostasis: causal or casual
      associations?

PMID- 14652626
TI  - Theme issue: Wound healing mechanisms.

PMID- 14652627
TI  - Regulatory roles of androgens in cutaneous wound healing.
AB  - Although the effects of androgens on wound healing are poorly characterised, the
      androgen receptor is expressed by inflammatory cells, keratinocytes and
      fibroblasts during wound healing, suggesting that androgens may regulate
      inflammatory and/or repair processes. In fact, it appears that endogenous
      testosterone inhibits wound healing and promotes inflammation since castration of
      male mice or systemic treatment with the androgen receptor antagonist flutamide
      accelerates cutaneous wound healing and reduces the inflammatory response. The
      aim of this review is to summarise our current knowledge about the regulation of
      tissue repair processes by androgens.

PMID- 14652628
TI  - Matricellular proteins as modulators of wound healing and the foreign body
      response.
AB  - Matricellular proteins form a group of extracellular matrix (ECM) proteins that
      do not subserve a primary structural role, but rather function as modulators of
      cell-matrix interactions. Members of the group, including thrombospondin (TSP)
      1,TSP-2, SPARC, tenascin (TN)-C, and osteopontin (OPN), have been shown to
      participate in a number of processes related to tissue repair. Specifically,
      studies in knockout mice have indicated that a deficiency in one or more of these
      proteins can alter the course of wound healing. More recently, TSP1, TSP2, and
      SPARC have also been implicated in the foreign body response, an unusual reaction
      to injury that occurs after the implantation of biomaterials. This review will
      focus on the roles of these proteins in the response to injury in mice and will
      show how studies of this pathophysiological process can elucidate some of the
      intrinsic properties of these matricellular proteins.

PMID- 14652629
TI  - Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue
      remodeling.
AB  - It is presently accepted that fibroblast/myofibroblast modulation represents a
      crucial step in granulation tissue contraction and in the production of the
      connective tissue deformations typical of fibrocontractive diseases. In addition
      to synthesizing extracellular matrix (ECM) components, myofibroblasts can develop
      tensile force through the neoformation of alpha-smooth muscle actin (alpha-SMA)
      containing cytoplasmic stress fibers. Tension has been shown to be a crucial
      regulator of connective tissue remodeling. In order to coordinate tension
      distribution within connective tissue, cell-matrix and cell-cell contacts appear
      essential. This review addresses the formation, molecular structure and function
      of such structures that are characterized by their association with
      intracytoplasmic actin filaments. Actin associated cell-matrix adhesions appear
      to provide the interface between ECM components and intracellular stress fibers,
      thus contributing to the transmission of force to the substrate and to the
      detection of stress level in the matrix. Cell-cell adherens junctions appear to
      synchronize myofibroblast contractile activity. Further studies investigating the
      functions of these structures will be important for the understanding of the
      mechanisms of granulation tissue evolution and for the planification of
      strategies in view of influencing connective tissue deformations.

PMID- 14652630
TI  - Fibrin glue for wound repair: facts and fancy.
AB  - In wound repair, fibrin has a multiplicity of activities, some of which are
      intrinsic to the protein itself and some attributable to other blood constituents
      associated with the fibrin clot. Fibrin sealants, which have been approved for
      hemostasis in the US and Europe, are occasionally used wounds to promote healing.
      However, inconsistency exists in the literature regarding the benefit of these
      preparations in the healing process. More crude fibrinogen preparations, such as
      cryoprecipitates made from the patient's own blood on location, appear from the
      literature to have better utility in wounds than more purified fibrinogen
      preparations available through commercial sources. These divergent outcomes are
      likely attributable to additional blood-derived products being associated with
      cryoprecipitates compared to the relatively purified commercial fibrinogen
      preparations. Clearly standard preparations and methods of application of fibrin
      sealant need to be defined for each particular surgical setting to resolve the
      many ostensible discrepancies in the current literature. A corollary is that
      different fibrin sealant preparations are likely to be preferable for different
      clinical situations.

PMID- 14652631
TI  - Soluble E-selectin in cardiovascular disease and its risk factors. A review of
      the literature.
AB  - The initial steps in the pathogenesis of atherosclerosis involve changes to the
      vascular endothelium, which produces numerous substances involved in the
      regulation and maintenance of vascular integrity and the homeostasis of the
      coagulation/fibrinolysis system. A further change in endothelial physiology is an
      increase in the surface expression of cell adhesion molecules, such as E
      selectin, which regulate adhesive interactions between certain blood cells and
      endothelium. As E-selectin is only expressed on activated endothelium, it
      therefore provides an opportunity to study pathophysiological aspects of this
      cell in cardiovascular and other disease. However, a soluble form of E selectin
      (i.e. sE-selectin) can be found in the plasma. This review will focus on sE
      selectin, and its potential role in the pathogenesis of cardiovascular disease as
      raised levels have been found in hypertension, diabetes and hyperlipidemia,
      although its association in established atherosclerosis disease and its value as
      a prognostic factor is more controversial.

PMID- 14652632
TI  - Fibrinogen B beta polymorphisms do not directly contribute to an altered in vitro
      clot structure in humans.
AB  - Fibrinogen B beta polymorphisms, such as the -455 G/A and the Arg448Lys amino
      acid substitution, have been shown to increase the risk of atherothrombotic
      disease. Although these polymorphisms are related to fibrinogen concentrations,
      their effect on fibrin clot structure has not been extensively studied. We
      examined the frequency of the fibrinogen B beta -455 G/A polymorphism in a group
      of myocardial infarction (MI) patients. There was no association between this
      polymorphism and MI. However, we found that patients homozygous for the rare -455
      A allele had a higher average age at first MI. A similar result was found for
      individuals homozygous for the B beta 448 Lys allele who also had a higher age at
      first MI. We subsequently studied the clotting properties of purified Arg448 and
      Lys448 fibrinogens in vitro and found that these fibrinogens did not
      significantly differ in their polymerisation, fibrinolysis kinetics or in their
      clot permeation properties. Mass spectrometry analysis of endoproteinase Asp-N
      digests of B beta chains revealed that the Lys(448) and the Arg(448) chains were
      expressed in approximately equal proportions in a heterozygote Arg448Lys
      individual. Our results demonstrate that the fibrinogen B beta -455 G/A
      polymorphism is not associated with myocardial infarction and further-more the
      closely linked B beta Arg448Lys protein coding variation does not have an
      influence on the function nor the structure of the protein in a purified system.

PMID- 14652633
TI  - Characterization of the human protein S gene promoter: a possible role of
      transcription factors Sp1 and HNF3 in liver.
AB  - Protein S is a vitamin-K-dependent plasma glycoprotein that serves as a cofactor
      for activated protein C in the protein C anticoagulation pathway, which regulates
      blood coagulation by inactivating factors Va and VIIIa. Mechanisms regulating the
      expression of the protein S gene remain unknown to date. The aim of this study
      was to characterize the cis-acting DNA elements of the human protein S gene in
      liver. We found that liver cell lines (HepG2 and PLC) transcribed the human
      protein S gene to mRNA, whereas non-liver cell lines (HEK293 and HeLa cells)
      either transcribed the gene weakly or not at all. Isolation and analysis of
      tissue-specific gene expression in HepG2 and HeLa cells of the 5'-flanking region
      from -6183 to +294 of the protein S gene indicated that the consensus binding
      motifs to HNF3 and Sp1 or MAZ transcription factors in the flanking region are
      essential for protein S gene expression. Exogenous expression of the Sp1 gene
      augmented the protein S-reporter gene expression in HepG2 or PLC cells but had no
      effect in HeLa cells. Taken together, we would conclude that transcription
      factors of HNF3, MAZ, and Sp1 are required for high-level expression of the
      protein S gene in hepatic cells, but in non-hepatic cells such as HeLa cells, an
      unknown factor(s) binds to the Sp1 region and disturbs the action of Sp1 and MAZ.

PMID- 14652634
TI  - Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis
      (383Trp stop codon and Cys529Tyr).
AB  - We investigated a family with prekallikrein deficiency, using both standard
      coagulation tests and molecular biology techniques. The propositus was found to
      be a compound heterozygote for a Trp383 stop codon and a Cys529Tyr point
      mutation. The former mutation was located in exon 11, the latter in exon 14. The
      propositus inherited the first defect from his father and the second from his
      mother. Both parents had slightly low prekallikrein levels, but the combination
      of the two genetic defects produced a phenotype characterized by an extremely low
      prekallikrein activity and antigen. The propositus' plasma showed a progressive
      reduction in APTT when incubated for a long time. Conversely, plasma deficient in
      factor XII, factor XI or high molecular weight kininogen (HMWK) failed to show
      shortening of the APTT. No circulating anticoagulant was found because the
      patient's APTT was fully corrected by pooled nor-mal and factor XII-, factor XI-
      or HMWK deficient plasma. No associated abnormality was apparent in the
      propositus or his parents. As expected, no tendency for bleeding was noted even
      after tonsillectomy.

PMID- 14652635
TI  - Therapeutic immunoglobulin reduces Ca2+ mobilization and von Willebrand factor
      secretion, and increases nitric oxide release in human endothelial cells.
AB  - Intravenous gamma-immunoglobulin (i.v.Ig) is commonly used in the treatment of
      autoimmune and inflammatory vascular disorders to prevent thrombotic
      complications. The mechanism of action of i.v.Ig is, however, not yet elucidated.
      In view of this, we investigated the ability of i.v.Ig to modulate i) Ca(2+)
      signals of fura-2 loaded endothelial cells, and ii) the associated release of
      nitric oxide (NO) and von Willebrand factor (vWf). NO was measured either
      indirectly by radioimmunoassay of cGMP in unstimulated cells or directly by
      electrochemistry at the surface of stimulated endothelial cells from human
      umbilical cord veins (HUVEC). Short-term treatment of unstimulated HUVEC with
      intact i.v.Ig decreased the basal cytosolic Ca(2+) concentration by 20% while it
      activated the NO/cGMP synthesis. Following i.v.Ig treatment of HUVEC, the Ca(2+)
      liberation from internal stores and the vWf secretion induced by ATP, thrombin or
      histamine were significantly reduced by 38 and 60%, respectively. The effects on
      Ca(2+) signals were observed with intact i.v.Ig as well as with the F(ab')2 or
      the Fc fragments indicating that both portions are involved in the mechanism of
      action. The i.v.Ig treatment of HUVECs had no effect on the NO release induced by
      thrombin or histamine. By contrast, the i.v.Ig treatment increased the ATP
      activated NO release by amplifying the Ser1177-eNOS phosphorylation. The i.v.Ig
      also activated the NO-dependent cGMP release in resting and collagen-stimulated
      platelets. Since NO is a potent inhibitor of platelet activation and vWF is a
      platelet adhesion cofactor, the beneficial effects of therapeutic i.v.Ig may lie
      in the inhibition of platelet adhesion to damaged endothelium.

PMID- 14652636
TI  - Blockade of GPIIb/IIIa by eptifibatide and tirofiban does not alter tissue factor
      induced thrombin generation in human endotoxemia.
AB  - Activated platelets facilitate thrombin generation by providing a catalytic
      surface on which coagulation activation occurs. The glycoprotein (GP) IIb/IIIa
      receptor might play a major role in this process as shown by in vitro and animal
      experiments. However, it is controversial whether the GPIIb/IIIa receptor
      facilitates tissue factor-induced thrombin generation in humans as well. We
      therefore investigated whether two clinically used GPIIb/IIIa antagonists
      (tirofiban and eptifibatide) may blunt TF-induced coagulation in humans. Thirty
      male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide,
      tirofiban or placebo over 5 hours in a randomized, double-blind, placebo
      controlled, double-dummy parallel-group trial. Markers of thrombin generation
      (prothrombin fragment 1+2, thrombin-antithrombin complexes), fibrinolysis (D
      dimer, plasmin-antiplasmin complexes) as well as inflammatory markers
      (interleukin-6, tumor necrosis factor-alpha) were measured by enzyme linked
      immunoasssays, TF-mRNA expression was quantified by RT-PCR. Neither eptifibatide
      nor tirofiban influenced LPS-induced coagulation activation or fibrinolytic
      activity. Additionally, the increase of TNF-alpha and IL-6 was similar in all
      groups. In conclusion, GPIIb/IIIa blockade with eptifibatide or tirofiban did not
      influence TF-induced coagulation activation in human low grade endotoxemia.

PMID- 14652637
TI  - Allele 4G of gene PAI-1 associated with prothrombin mutation G20210A increases
      the risk for venous thrombosis.
AB  - Several studies have tried to clarify the role of polymorphism 4G/5G of the PAI-1
      gene in venous thromboembolism without reaching any final conclusion. It has been
      demonstrated that this polymorphism may induce an increased risk for venous
      thromboembolism (VTE) in patients with thrombophilic defects. We studied the
      association of prothrombin mutation G20210A with 4G/5G polymorphism in 402 VTE
      patients and 466 healthy controls. Patients affected by prothrombin mutation
      G20210A, with or without the concomitant presence of allele 4G, had a 3.7
      thrombotic risk (C.I. 95% 2.3-6.0; p<0.0001). Moreover, genotype 4G/4G is a mild
      risk factor for VTE, irrespectively of whether the prothrombin mutation was
      present. Logistic regression analysis showed that patients carrying the G20210A
      prothrombin mutation with allele 4G gave an odds ratio for VTE of 6.1 (C.I. 95%
      3.2-11.4; p<0.001). The risk increased up to 13.0 (C.I. 95% 3.0-60.4; p<0.001)
      when we considered the association of the prothrombin mutation with genotype
      4G/4G. The G20210A mutation without allele 4G (5G/5G) was not a risk factor for
      VTE. In conclusion, we believe that patients affected by VTE with concomitant
      presence of the G20210A prothrombin mutation could be tested for genotype 4G/4G
      to better define their thrombotic risk.

PMID- 14652638
TI  - Blood coagulation and fibrinolysis before and after exhaustive exercise in
      patients with IDDM.
AB  - Diabetes mellitus involves changes in haemostasis which leads to the opinion that
      diabetes mellitus is a hypercoagulable state. However, little is known about the
      relationship of exercise and haemostasis in diabetics. Therefore, first of all
      the aim was to investigate if differences in blood coagulation and fibrinolysis
      can be demonstrated in subjects with insulin-dependent diabetes mellitus (IDDM)
      compared to controls and secondly, if differences concerning exercise induced
      changes can be seen in diabetics. 16 moderately fit subjects with IDDM and 16
      matched controls underwent a maximal step test. Blood samples were taken after a
      30 min rest, immediately and 1h after exercise and in addition after 30 min rest
      7 days later at the same time of day. The rest values (mean of the two rest
      samples) in extrinsic total thrombin potential (TTPex, P=0.049), tPA-activity
      (P=0.007) were significantly higher and in PAI-1-antigen (P=0.002) -activity
      (P=0.049) lower in the diabetic group. APTT, PT, TAT (only control), TTPin, tPA
      activity and -antigen and PAP were increased immediately and D-dimer (only
      control) 1 h after exercise, whereas PAI-1-activity and -antigen (only control)
      decreased immediately or 1 h after exercise (all minimal P<0.05). The increase of
      tPA-antigen and decrease in PAI-1-antigen after exercise were both lower in the
      diabetics (P<0.05). IDDM led to higher extrinsic total thrombin and fibrinolytic
      potential at rest, and reducing the exercise provoked distribution of tPA-antigen
      and decrease of PAI-1-antigen. Nevertheless a higher thrombotic risk after
      maximal exercise has not been investigated in young IDDM patients without
      complications and in good metabolic control.

PMID- 14652639
TI  - Circulating levels of inflammatory cytokines (IL-1 beta and TNF-alpha),
      resistance to activated protein C, thrombin and fibrin generation in
      uncomplicated pregnancies.
AB  - We studied 33 women during normal uneventful pregnancies and with no history of
      previous adverse pregnancy events for markers of activated coagulation and
      thrombin activity including prothrombin fragment 1.2(PF1.2), thrombin-
      antithrombin (TAT), and soluble fibrin polymer (SFP). In addition, we measured
      potential thrombin generation through the addition of thromboplastin to patient
      plasma in the presence of a thrombin-specific chromogenic substrate determined
      serially over a period of time--Endogenous Thrombin Potential assay (ETP). This
      assay was performed with plasma treated and untreated with activated protein C
      (APC). The fibrinolytic system was assessed by measurement of thrombin
      activatable fibrinolysis inhibitor (TAFI). These findings were correlated with
      the levels of pro-inflammatory cytokines, interleukine-1 beta and tumor necrosis
      factor-alpha. Our data supports previous reports that indicate that resistance to
      activated protein C and coagulation activation markers are commonly increased in
      the later 2/3rds of pregnancy. There are no differences in thrombin generation
      potential, as determined by the ETP assay without the addition of APC, in the
      three trimesters. However, the thrombin reserve (TR), the ETP result without APC
      divided by the ETP result with the addition of APC, is increased above the
      reference range in the 2nd and 3rd trimesters. Patients with increased TR and
      resistance to APC had increased levels of TNF-alpha. Increased proinflammatory
      cytokines are reportedly associated with changes in the APC system with a
      decrease in the ability to generate APC. A sub-group of pregnancies with APC
      resistance had increased levels of TNF-alpha and may be important in the risk for
      adverse pregnancy outcomes.

PMID- 14652640
TI  - The effects of different alcoholic drinks on lipids, insulin and haemostatic and
      inflammatory markers in older men.
AB  - Light to moderate drinking is associated with lower risk of coronary heart (CHD)
      than non-drinkers. We have examined the relationships between total alcohol
      intake and type of alcoholic beverage and several potential biological
      mechanisms. We carried out the study in 3158 men aged 60-79 years drawn from
      general practices in 24 British towns with no history of myocardial infarction,
      stroke or diabetes and who were not on warfarin. Total alcohol consumption showed
      a significant positive dose-response relationship with high density lipoprotein
      cholesterol (HDL-C), coagulation factor IX, haematocrit, blood viscosity, and
      tissue plasminogen (t-PA) antigen, and an inverse dose-response relationship with
      insulin, fibrinogen, von Willebrand factor (vWF) and triglycerides after
      adjustment for possible confounders. Total alcohol consumption showed weak
      associations with plasma viscosity and fibrin D-dimer, and no association with
      factors VII, VIII, or C-reactive protein (CRP). Wine was specifically associated
      with lower CRP, plasma viscosity, factor VIII and triglycerides. The findings are
      consistent with the suggestion that HDL-C in particular but also insulin and
      haemostatic factors may contribute to the beneficial effect of light to moderate
      drinking on risk of CHD. Wine has effects that may confer greater protection than
      other alcoholic beverages.

PMID- 14652641
TI  - A multi-centre collaborative study on the potency estimation of ReFacto.
AB  - Seven laboratories estimated factor VIII coagulant activity in recombinant B
      domain-deleted (ReFacto) and plasma-derived FVIII concentrates (Octonativ-M)
      using chromogenic methods relative to the WHO 6th International Standard FVIII
      Concentrate (WHO 6th IS), European Pharmacopoeia BRP#2 (EP#2) and the ReFacto
      Laboratory Standard (RLS). Significantly higher estimates were obtained for all
      batches of product when calculated relative to the RLS in comparison with
      estimates vs WHO 6th IS and EP#2. Mean estimates for two batches of ReFacto
      product vs the RLS were within 10% of the labelled potency whereas estimates vs
      WHO 6th IS and EP#2 ranged from 21 to 31% lower than the label. Conversely, mean
      estimates for Octonativ-M relative to WHO 6th IS and EP#2 were within 10% of the
      label whereas the mean estimate vs RLS was 117% of label. Mean estimates for the
      ReFacto product, vs the WHO 6th IS and EP#2, varied considerably between the
      different chromogenic kits whereas estimates vs the RLS showed good agreement
      between kits. Mean estimates for the RLS vs the WHO 6th IS (8.10 IU/vial) and the
      EP#2 (7.66 IU/vial) were lower than the assigned value of 9.4 IU/vial. The
      results are consistent with ReFacto and full-length FVIII responding differently
      to variations in assay methodology and also indicate that the assigned value on
      the RLS may be too high. Since this study the unitage on the RLS has been
      adjusted to effectively increase the amount of ReFacto in the product by 20%.

PMID- 14652642
TI  - Hemostatic risk factors in ischemic stroke.
AB  - The role played by hemostasis in the pathogenesis of ischemic stroke is still
      controversial. In the present study, we looked for a possible association of
      ischemic stroke and high clotting activity of factor II (FII:C), factor V (FV:C),
      factor VII (FVII:C), factor X (FX:C) and fibrinogen. We investigated 157 non-anti
      coagulated patients (86 males, 71 females; median age 41 y, range 16-73 ), who
      had survived ischemic stroke for at least 2 months, and 193 healthy controls with
      similar age and sex distribution (104 males, 89 females; median age 39 y, range
      19-74). Patients showed significantly higher body mass index, as well as
      significantly higher prevalence of arterial hypertension, smoking and
      hyperlipidemia. FV:C (p = 0.05), FX:C (p = 0.04) and fibrinogen (p = 0.05) were
      higher in patients as compared to controls. In a univariate risk analysis FX:C
      and FV:C were associated with the relative risk for ischemic stroke showing an
      odds ratio (OR) of up to 2.8 (95% CI: 1.05-7.6) and 3.4 (95%CI: 1.4-7.9),
      respectively, for levels above 130%. In a multivariate analysis using a logistic
      regression model including age, sex, arterial hypertension, smoking habit,
      diabetes, hyperlipidemia, BMI and the coagulation factors, FV:C was still found
      to significantly (p=0.03) add to the risk of ischemic stroke. An increase of
      factor FV:C by 10% was associated with an increase in the relative risk of 19%
      (95% CI.: 2%-38%). In conclusion, we found a high plasma level of FV:C to be a
      prevalent (FV:C > 130% in 20/157 patients) and independent risk factor for
      ischemic stroke.

PMID- 14652643
TI  - Reduction of venous thromboembolism following prolonged prophylaxis with the low
      molecular weight heparin Certoparin after endoprothetic joint replacement or
      osteosynthesis of the lower limb in elderly patients.
AB  - The peri- and postsurgical thromboembolic prophylaxis with low molecular weight
      heparins is a well established therapy regimen, but the optimum duration of
      prophylaxis after surgery still remains uncertain. A few studies have pointed to
      the fact that the thromboembolic risk of high-risk patients persists longer than
      the in-hospital period correlating with respective hypercoagulatory conditions.
      The aim of the present study was to test if a prolongation of thromboprophylaxis
      with the low molecular weight heparin Certoparin further reduces the rate of
      thromboembolism in high-risk patients after orthopedic surgery. The "Long-term
      Thromboprophylaxis"-Study was a multicenter, randomized, double-blind, placebo
      controlled trial. 360 patients who underwent endoprothetic joint replacement or
      osteosynthesis of the lower limb were initially enrolled, all of them received
      prophylactically 3000 U anti-Xa of Certoparin once daily for 14 days followed by
      randomization to prolonged Certoparin application or to placebo up to day 42.
      Patients were screened for deep vein thrombosis by sonography every week.
      Coagulation markers (fibrin monomers and D-dimers) were determined during the
      course of the study. Venous thromboembolism during the prolongation period was
      observed in 18 patients receiving placebo versus 8 patients of the prolonged
      Certoparin group (12.1% versus 5.0%, intention-to-treat sample). The analysis
      revealed a statistically significant difference in favor of Certoparin (p=0.020),
      which was confirmed by per-protocol analysis (14.2% versus 5.5%, p=0.012). The
      differences remained significant, if analyses considered only clinically
      symptomatic thromboembolic events (p=0.040). Patients who developed a thrombosis
      showed a strong increase of coagulation markers as compared to patients without
      subsequent thrombosis. The respective differentiation started around 18 days
      before diagnosis of thrombosis. Only one minor bleeding complication was observed
      during prolonged Certoparin prophylaxis. The present study shows that patients
      after joint replacement or osteosynthesis of the lower extremities have a
      persisting risk to develop thromboembolic complications beyond the routine
      duration of thromboprophylaxis. Extended prophylaxis with Certoparin resulted in
      a significantly lower rate of thromboembolism and should be strongly recommended.

PMID- 14652644
TI  - Cost-effectiveness of two models of management for patients on chronic warfarin
      therapy--a Markov model analysis.
AB  - Allocation of additional resources for establishing or expanding anticoagulation
      clinic (AC) services is a significant concern for healthcare decision-makers when
      the payer is also the provider of the healthcare system. The majority of
      anticoagulated patients in Hong Kong are managed by routine medical care (RMC)
      instead of ACs, possibly due to the lack of local cost-effectiveness analysis of
      the AC setting. The aim was to compare the clinical and economic outcomes of
      anticoagulated patients who were managed by AC or RMC from the perspective of a
      public health organization in Hong Kong. A Markov model was designed to simulate,
      over 10 years, the economic and clinical outcomes of patients receiving chronic
      warfarin therapy managed by AC or RMC. The transition probabilities were derived
      from literature. Resource utilization was retrieved from patients managed by AC
      and RMC in Hong Kong. Sensitivity analysis was conducted to examine the
      robustness of the model. The total number of events per 100 patient-years and the
      direct medical cost per patient-year in the AC and RMC groups were 9.5 and USD
      840, and, 19.3 and USD 1,179, respectively. The results of the model were
      sensitive to the variation of the probability of major bleeding in the AC group.
      In conclusion, the coordinated care provided by an anticoagulation clinic appears
      to be more cost-effective than routine medical care in the management of warfarin
      therapy from the perspective of public health organization in Hong Kong.

PMID- 14652645
TI  - Platelet factor 4 localization in carotid atherosclerotic plaques: correlation
      with clinical parameters.
AB  - Emerging evidence supports a role for platelets in the progression of
      atherosclerosis in addition to an involvement in thrombotic vascular occlusion.
      Platelet Factor 4 (PF4), a chemokine released by activated platelets, stimulates
      several pro-atherogenic processes. Therefore, we examined the localization of PF4
      and the homologous protein, Neutrophil Activating Protein-2 (NAP-2) in lesions
      representing the evolution of human atherosclerotic plaques. Carotid plaques from
      132 patients with critical carotid stenosis and 6 autopsy specimens were studied.
      Clinical, histologic and immunohistochemical data were analyzed using a chi(2)
      test. PF4 was detected in the cytoplasm of luminal and neovascular endothelium,
      in macrophages and in regions of plaque calcification. The presence of PF4 in
      macrophages and neovascular endothelium correlated with lesion grade (p = 0.004;
      p = 0.044). Staining of macrophages for PF4 correlated with the presence of
      symptomatic atherosclerotic disease (p = 0.028). In early lesions, PF4 was
      commonly found in macrophages of early lesions (Grade I/II), whereas NAP-2 was
      rarely present. In conclusion, correlation between PF4 deposition, lesion
      severity and symptomatic atherosclerosis suggests that persistent platelet
      activation may contribute to the evolution of atherosclerotic vascular lesions.
      These studies support the rationale for the chronic use of anti-platelet therapy
      in patients at risk for developing symptomatic atherosclerosis.

PMID- 14652646
TI  - Intracellular alkalinization augments capacitative Ca2+ entry in platelets.
AB  - In order to elucidate the significance of intracellular alkalinization in signal
      transduction of platelets, we investigated the effects on capacitative Ca(2+)
      entry (CCE) of intracellular alkalinization that was induced by NH(4)Cl. Addition
      of NH(4)Cl (10 mM) to the medium resulted in an elevation of intracellular pH by
      about 0.35, which was eliminated by simultaneous addition of propionate (20 mM),
      an inducer of intracellular acidification, to the medium. CCE was induced by an
      extracellular addition of Ca(2+) to platelets in which Ca(2+) stores had been
      depleted by stimulation with thapsigargin in nominally Ca(2+)-free medium.
      NH(4)Cl markedly augmented CCE and subsequent platelet aggregation, both of which
      were abolished in the presence of SKF-96365, an inhibitor of capacitative Ca(2+)
      entry in non-excitable cells such as platelets. The augmentation of CCE and
      subsequent aggregation by NH(4)Cl was not observed in the presence of propionate
      or SKF-96365. Extracellular alkalosis induced by Tris also markedly augmented CCE
      and subsequent aggregation. These augmenting effects of extracellular alkalosis
      by Tris were significantly but incompletely inhibited by simultaneous addition of
      propionate (20 mM), which completely eliminated elevation of intracellular pH
      elicited by Tris. Thus, the augmenting effect of extracellular alkalosis on CCE
      was in part mediated by intracellular alkalosis. These findings suggest that
      intracellular alkalinization is a potent signal that augments CCE in platelets.

PMID- 14652647
TI  - Increased leukocyte-platelet adhesion in patients with graft occlusion after
      peripheral vascular surgery.
AB  - Graft occlusion following peripheral vascular surgery is attributable to some
      combination of acute thrombosis, and progression of atherosclerosis: interactions
      between leukocytes and activated platelets may play a role in both of these
      processes. This investigation measured perioperative leukocyte-platelet conjugate
      formation, and leukocyte and platelet activation in 46 patients undergoing
      surgery for lower extremity peripheral vascular disease (PVD). All patients were
      followed for graft patency over the next 6 months; 27 patients had grafts that
      remained patent while 19 had graft occlusion. On postoperative day #1 (POD#1),
      the graft occlusion group demonstrated a significantly greater increase in
      circulating levels of both monocyteplatelet and neutrophil (PMN)-platelet
      conjugates compared to the patent graft patients (p=0.015 and 0.018,
      respectively). PMN activation, assessed by increases in surface CD11b expression,
      was also significantly increased on POD#1 in the graft occlusion group compared
      to the patent group (p=0.026). The percentage of circulating activated (CD62P+)
      platelets did not differ between groups, but patients with graft occlusion
      demonstrated a higher percentage of younger, reticulated plate-lets throughout
      the study period (p=0.008), indicating increased platelet turnover. We conclude
      that in the early postoperative period, leukocyte-platelet adhesion, PMN
      activation, and platelet turnover are significantly greater in PVD patients who
      go on to develop later graft occlusion. Cellular activation and heterotypic cell
      interactions in peripheral vascular surgery patients may be important in the
      etiologies of thrombosis and/or accelerated atherosclerosis leading to graft
      loss.

PMID- 14652648
TI  - Platelet membrane glycoprotein polymorphisms do not influence the clinical
      expressivity of von Willebrand disease type 1.
AB  - Von Willebrand disease (VWD) is characterized by a significant variation in
      bleeding symptoms among patients with similar laboratory profiles and equivalent
      plasma levels of von Willebrand factor (VWF) activities. Considering the recent
      suggestion that platelet membrane glycoprotein polymorphisms (PltGPs) may play a
      role as modulators of thromboembolic or haemorrhagic diseases, we investigated
      the role of different PltGPs and GPVI content in the clinical expression of
      patients with VWD type 1.The diagnosis of VWD (n = 76) was based on laboratory
      findings (VWF:Ag, VWF:RCo, VWF:CB, FVIII:C, and multimer analysis), family and
      personal history of bleeding. All patients were interviewed using a standardized
      questionnaire, and classified into two categories: bleeders (unequivocal bleeding
      tendency, n = 53) and non bleeders (absence of bleeding symptoms, n = 23).
      PltGPs, HPA-1, 2 and 5 and C807T of GPIa were determined by fluorophore-labelled
      hybridization probes on a LightCycler. GPVI content was measured by western
      blotting. VWF:Ag,VWF:RCo,VWF:CB and FVIII:C levels were not significantly
      different between symptomatic and asymptomatic patients. There were no
      differences in the genotype distribution and allele frequencies between bleeders
      and non bleeders for the platelet alloantigen systems HPA-1, 2, 5 and the GPIa
      C807T polymorphism. The levels of platelet GPVI were similar in symptomatic and
      asymptomatic VWD patients (109.6 +/- 58.4 vs 114.1 +/- 52.5, respectively; p:
      0.77). These results show that PltGPs HPA-1, 2 and 5 or the C807T dimorphism of
      GPIa do not influence the clinical expressivity of VWD type 1. The wide variation
      in GPVI content was not associated with the severity of bleeding in the patients.
      Other genetic factors that may contribute to the variable expressivity of VWD
      type 1 should be investigated.

PMID- 14652649
TI  - Increased neutrophil mediator release in patients with pulmonary hypertension-
      suppression by inhaled iloprost.
AB  - Polymorphonuclear neutrophils (PMN) have been implicated in various vascular
      inflammatory processes. We isolated PMN from venous blood samples of 10 patients
      with severe primary pulmonary arterial hypertension (PPH), 7 patients with
      pulmonary hypertension secondary to chronic thromboembolism (CTEPH), and 12
      healthy controls. When stimulated with the calcium-ionophore A23187, platelet
      activating factor (PAF) or the microbial agent n-formyl-Methionyl-Leucyl
      Phenylalanine (fMLP), significantly increased release of elastase and superoxide
      anion was noted in both groups with pulmonary hypertension. Moreover, the
      neutrophils of CTEPH patients responded with an enhanced liberation of
      leukotriene (LT) B(4) and 5-hydroxyeicosatetraenoic acid (5-HETE). Inhalation of
      aerosolized iloprost (5 microg) caused a rapid decline in pulmonary vascular
      resistance, in both PPH and CTEPH. This hemodynamic response was paralleled by a
      significant suppression of ionophore- and ligand-induced elastase and superoxide
      release, as well as LTB(4) and 5-HETE formation. The neutrophil inhibitory effect
      of the inhalation maneuver was fully reproduced by in vitro incubation of
      neutrophils with 1-10 pg/ml iloprost for 2 hours. This is the first study to
      demonstrate that circulating neutrophils from patients with PPH and CTEPH possess
      an enhanced readiness to respond with inflammatory mediator generation to
      different stimulatory agents ex-vivo, and that PMN respiratory burst, elastase
      secretion and leukotriene generation are promptly reduced by an iloprost
      inhalation maneuver. Neutrophils might participate in the inflammatory processes
      in pulmonary arterial hypertension.

PMID- 14652650
TI  - Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial
      adherence of neutrophils by antithrombin.
AB  - Circulating endotoxin is elevated in sepsis and plays a role in endothelial
      dysfunction whereas antithrombin is decreased by virtue of its consumption during
      complex formation with clotting factors and by proteolytic degradation by
      granulocyte elastase. Dysfunction of endothelium results in enhanced leukocyte
      rolling and diapedesis into tissues leading to edema formation and injury.
      Antithrombin exerts beneficial effects on endothelial function in sepsis. A
      direct anti-inflammatory action of anti-thrombin in inflammatory cells is exerted
      via heparan sulfate proteoglycans. In this study, we investigated whether
      antithrombin affects endotoxin-induced adhesion of neutrophils to human
      endothelial cells in vitro and whether glycosaminoglycans are involved in its
      signaling. Adhesion of human neutrophils to monolayers of umbilical vein
      endothelial cells was tested under static conditions. Endothelial cells were
      pretreated with endotoxin, interleukin-1, heparinase-I, chondroitinase-ABC or
      anti-syndecan-4-antibody. Endotoxin and interleukin-1 increased neutrophil
      adherence to human umbilical vein endothelial cells which was inhibited by
      antithrombin. Concomitant incubation with pentasaccharide abolished this effect
      of antithrombin. Treatment of endothelial cells with heparinase or chondroitinase
      led to higher adhesion and prevented effects of antithrombin. With antibodies to
      syndecan-4, enhanced adhesion of neutrophils was observed. As studied by Western
      blotting, endotoxin-induced signaling was diminished by antithrombin and the
      effect was reversible by chondroitinase or heparinase. From our results, we can
      conclude that endotoxin-induced adhesion of leukocytes to endothelium can be
      reversed by ligation of syndecan-4 with antithrombin's heparin-binding site and
      interferences with stress response signaling events in endothelium.

PMID- 14652651
TI  - Thrombophilic mutations in high-risk atrial fibrillation patients: high
      prevalence of prothrombin gene G20210A polymorphism and lack of correlation with
      thromboembolism.
AB  - Atrial fibrillation (AF) is a common arrhythmia that results in a high risk of
      cerebral and peripheral embolism. Factor V Leiden and factor II G20210A variant
      are two leading conditions for venous thrombosis. The aim of our study was to
      find out whether these two common prothrombotic mutations play a role in the
      occurrence of embolic events in AF patients. We investigated 336 non-valvular AF
      patients and 336 healthy control subjects. Factor II G20210A variant was found in
      24/336 patients (7.14%) and in 11/336 of control subjects (3.3%). At a
      multivariate analysis, factor II G20210A variant was independently associated to
      AF (OR 2.4 95% CI 1.1-5.2; p<0.05). No significant difference was observed in the
      prevalence of factor V Leiden in the two groups investigated [6/304 (2.0%) in
      patients vs 13/336 (3.9%) in controls (p=0.24)]. AF patients were separately
      analyzed in relation to the occurrence or absence of a cerebral or peripheral
      embolic event (200 with and 136 without embolic event). The prevalence of the two
      mutations among AF patients with and without an embolic event was similar [factor
      II G20210A polymorphism (7% and 7.3% respectively) and factor V Leiden (1.2% and
      2.9%, respectively)]. No differences were found in relation to the type of
      embolic event. Our results suggest a possible relationship between the presence
      of prothrombin gene variant and AF per se.

PMID- 14652652
TI  - High D-dimer levels predict cardiovascular events in patients with chronic atrial
      fibrillation during oral anticoagulant therapy.
AB  - Atrial fibrillation (AF) is associated with hemostatic abnormalities and
      increased risk of thrombotic cardiovascular events even during oral anticoagulant
      therapy (OAT). The aim of our study was to evaluate the predictive value of
      hemostatic markers for the risk of major cardiovascular events during OAT. The
      study group comprised 113 patients with chronic AF (70.2 +/- 5.4 years old, 60%
      men), referred for OAT. Established clinical risk factors and levels of
      prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), D-dimer,
      tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1)
      antigen and activity, before and during OAT (after 3.9 +/- 0.7 months; INR 2.57
      +/- 0.57) were determined. In all patients OAT significantly suppressed levels of
      F1+2 by 67%,TAT by 30% and D-dimer by 48% (all p <0.001). During an average
      follow-up of 44 months 22/111 (20%) patients suffered a combined cardiovascular
      event (stroke, myocardial infarction, peripheral vascular occlusion or vascular
      death). Patients with cardiovascular events were significantly older, had more
      frequent heart failure/systolic dysfunction and had significantly increased
      levels of D-dimer at entry (63 vs 39 ng/mL, p = 0.005) and during OAT (33 vs 18
      ng/mL, p = 0.002), and of t-PA antigen at entry (14.3 vs 10.9 ng/mL, p = 0.02)
      and during OAT (15.0 vs 11.2 ng/mL, p = 0.05) (all values are medians). In
      multivariate Cox proportional hazard models, heart failure/systolic dysfunction
      (hazard ratio 2.91; 95% CI 1.17-7.26; p = 0.02), high levels of D-dimer on OAT
      (top vs. lower two quartiles) (hazard ratio 4.78, 95% CI 1.39-16.41; p = 0.01)
      and t-PA antigen levels (continuous variable) (hazard ratio 1.09; 95% CI 1.01
      1.17; p = 0.02) were significantly associated with combined cardiovascular
      events. In conclusion, high levels of D-dimer and t-PA antigen during OAT are
      significant predictors of combined cardiovascular events in AF patients and, on
      this basis, could be useful additional markers of cardiovascular risk in such
      patients.

PMID- 14652653
TI  - Low protein Z plasma levels are independently associated with acute coronary
      syndromes.
AB  - Protein Z (PZ) is a single chain vitamin-K-dependent glycoprotein synthesized by
      the liver. Studies in vivo and in vitro suggest that PZ plays an important role
      in inhibiting coagulation as it serves as cofactor for the inactivation of factor
      Xa by forming a complex with the plasma PZ-dependent protease inhibitor.
      Recently, conflicting findings on plasma PZ levels in patients with ischemic
      stroke have been published. Aim of our study was to investigate the role of PZ in
      acute coronary syndromes (ACS). PZ plasma levels were determined in 223 (189 M;
      34 F) patients with ACS referring to the Coronary Intensive Therapy Unit of
      University of Florence and in 265 (219 M; 46 F) healthy subjects. Patients under
      oral anticoagulation treatment as well as subjects with positivity for
      antiphospholipid antibodies were excluded. None had liver or kidney dysfunction.
      The mean PZ plasma level was lower in patients (1508 +/- 730 ng/mL) than in
      controls (1728 +/- 594 ng/mL) (p < 0.0001). PZ levels below the 5th percentile
      (565 ng/mL) of normal values distribution in control subjects were found in 15.7%
      of patients and in 4.9% of controls (p <0.0001). At multivariate analysis, PZ
      levels below 565 ng/mL were associated with ACS (OR=3.3; 99%CI 1.1-9.7; p =
      0.004). The contemporary presence of low PZ levels and smoking habit leads to an
      increased risk of ACS (OR=9.5; 99%CI 2.4-37.2; p < 0.0001). In conclusion, our
      results suggest a possible role of PZ in the occurrence of arterial thrombosis.

PMID- 14652654
TI  - Accumulation of radiolabelled platelets and fibrin on the carotid artery of
      rabbits after angioplasty: effects of heparin and dipyridamole.
AB  - We investigated the dynamic accumulation of platelets and fibrin after balloon
      injury of the carotid arteries in rabbits in vivo. In addition, effects of
      heparin and dipyridamole treatment were also tested. Autologous (99m)Tc-labelled
      platelet and (123)I-labelled fibrin accumulation was measured at one minute
      intervals for 4 hours following balloon injury of the carotid artery. Platelet
      accumulation occurred rapidly, with an approximately 125% increase occurring
      within 30 min after injury. There was no further activity for up to 4 hours. This
      accumulation could be inhibited with an intravenous infusion of PGI2 (500
      ng/kg/hr). Fibrin accumulation occurred slowly and continuously over the 4 hour
      measurement period. Injection of an anti-fibrin antibody inhibited fibrin
      accumulation. Heparin (25 U/kg/hr for 4 hrs) administration resulted in a
      significant 82 +/- 19% and 68 +/- 13% reduction in platelet and fibrin
      accumulation, respectively. This dose of heparin was associated with a 2-fold
      prolongation of the aPTT. Dipyridamole (0.45 mg/kg/hr for 4 hrs) resulted in a 46
      +/- 12% and 70 +/- 25% reduction of platelet and fibrin accumulation,
      respectively. Thus, we demonstrated that the dynamics of platelet and fibrin
      accumulation following balloon injury in rabbits are very different. The vessel
      wall continues to be thrombogenic for fibrin up to 4 hours after injury even
      though platelet accumulation has ceased after one hour. We conclude that the
      local thrombotic events following balloon injury are complex and that not only
      platelets but also fibrin is important in regulating responses to injury.

PMID- 14652655
TI  - Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of
      angiographic coronary restenosis.
AB  - The fibrinolytic system is closely related to several processes that are involved
      in restenosis. We previously showed that low PAI-1 plasma levels predicted
      restenosis. Recently, a different fibrinolytic inhibitor, TAFI, has been
      described. The aims of this study were to evaluate the relationship between pre
      procedural plasma levels of TAFI and late angiographic restenosis and the
      interaction between TAFI and PAI-1.We prospectively studied 159 patients with
      stable angina who underwent successful elective angioplasty or stenting of de
      novo native coronary artery lesions. TAFI and PAI-1 antigen levels were measured
      in plasma samples drawn before the procedure. Follow-up coronary angiography was
      performed in 92% of patients. There was a significant correlation between pre
      procedural TAFI levels and 6-month % diameter stenosis (DS) (r = 0.21; p =
      0.013). The overall angiographic restenosis rate (DS>50%) was 31%. Pre-procedural
      TAFI levels were significantly higher in patients with restenosis (108 +/- 33%
      versus 94+/-30%, p = 0.011). Restenosis rates for patients in the upper tertile
      of TAFI levels were 2-fold higher than for those in the lowest tertile (45%
      versus 22%; p = 0.016). A combination of high TAFI and low PAI-1 levels
      identified patients at the highest risk of restenosis (53%) compared to 14% in
      patients with low TAFI and high PAI-1 levels; p = 0.027. In conclusion, pre
      procedural plasma TAFI antigen levels identify patients at increased risk for
      restenosis after PCI.

PMID- 14652656
TI  - Markers of endothelial activation and atherothrombosis in women with history of
      preeclampsia or gestational hypertension.
AB  - Women who have had preeclampsia (PE) or gestational hypertension (GH) exhibit
      relatively high rates of circulatory diseases. PE is a disease associated with
      inflammation and vascular endothelial dysfunction. We therefore hypothesised that
      women with a history of PE or GH might have abnormal levels of markers of
      endothelial activation or inflammation, reflecting either an innate
      predisposition to preeclampsia or changes induced by the eclamptic process.
      Levels of von Willebrand factor, fibrinogen and C-reactive protein were compared
      in 392 women with a history of PE between 1951 and 1970, 297 women with a history
      of GH and 163 matched controls. Although no significant differences between those
      with either PE or GH and controls were noted, subjects with a history of PE had
      significantly higher CRP values than those with GH. No significant differences
      were found when the three groups were compared for von Willebrand factor or
      fibrinogen. Overall, the data do not support our hypothesis. In addition, our
      data document increasing von Willebrand factor levels increase with age, which
      may help explain the age dependent increase in venous or arterial thrombosis.
      Moderate alcohol consumption was also associated with lower levels of
      inflammatory markers.

PMID- 14652657
TI  - Exclusion of pulmonary embolism using C-reactive protein and D-dimer. A
      prospective comparison.
AB  - Our goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone
      or combined with clinical probability assessment in patients with suspected
      pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We
      conducted a prospective study in which we performed a common immuno-turbidimetric
      CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in
      259 consecutive outpatients with suspected PE at the emergency department of a
      teaching hospital. We assessed clinical probability of PE by a validated
      prediction rule overridden by clinical judgment. Patients with D-dimer levels >
      or = 500 microg/l underwent a work-up consisting of lower-limb venous ultrasound,
      spiral computerized tomography, ventilation-perfusion scan, or pulmonary
      angiography. Patients were followed up for three months. Seventy-seven (30%) of
      the patients had PE. The CRP alone had a sensitivity of 84% (95% confidence
      interval [CI).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% CI:
      78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low
      clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE
      (9%) in this subgroup, the NPV increased to 97% (95% CI: 89 to 100%). The D-dimer
      (cutpoint 500 micro g/l) showed a sensitivity of 100% (95% CI: 95 to 100%) and a
      NPV of 100% (95% CI: 94 to 100%) irrespective of clinical probability and
      accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined
      with clinical probability assessment cannot safely exclude PE.

PMID- 14652658
TI  - Evaluation of ADAMTS-13 activity in plasma using recombinant von Willebrand
      Factor A2 domain polypeptide as substrate.
AB  - The metalloprotease ADAMTS-13 cleaves von Willebrand factor (VWF), and is absent
      or severely reduced in the plasma of patients with thrombotic thrombocytopenia
      purpura (TTP). Under physiologic flowing conditions, the enzyme cleaves
      endothelial cell-derived ultra-large VWF multimers at the Y842/M843 peptide bond
      located in the A2 domain, where many mutations associated with Type 2A VWD
      cluster. These VWF mutants are more susceptible for cleavage activity, decreasing
      the large VWF multimers in the plasma. The susceptibility of a recombinant VWF-A2
      domain to ADAMTS-13 and the potential application in detecting enzyme activity
      were investigated. In vitro, fluid phase cleavage of VWF by ADAMTS-13 requires
      denaturing conditions and prolonged incubation in order to estimate enzyme
      activity. We have measured ADAMTS-13 activity based on enzyme cleavage of a
      recombinant VWF-A2 domain under non-denaturing conditions. In our assay, enzyme
      activity was absent in plasma from congenital and acquired TTP patient, and
      blocked by each EDTA, monoclonal antibody VP-1 (peptide-specific antibody against
      residues 828-842 of VWF), and an ADAMTS-13 antibody purified from plasma of an
      acquired TTP patient. This novel recombinant VWF-A2 protein has potential utility
      as matrix for a rapid clinical measurement of plasma ADAMTS-13 activity.

PMID- 14652659
TI  - Phenprocoumon-induced hepatitis as an immunologically mediated drug allergic
      complication of antithrombotic therapy.

PMID- 14652660
TI  - In vitro high level protein S expression after modification of protein S cDNA.

PMID- 14652661
TI  - Thrombolysis in pregnancy.

PMID- 14652662
TI  - Fc gamma RIIa-R131H polymorphism: its impact on coronary heart disease in a
      German cohort.

PMID- 14652663
TI  - Variation of factor VII 140s and 170s loops in fishes: evolutionary aspects and
      comparison with mutations found in FVII deficiency.

PMID- 14652664
TI  - Drotrecogin alfa (activated) prolongs half-life time of messenger RNA encoding
      for interleukin-8 and monocyte chemoattractant protein-1.

PMID- 14652665
TI  - Association analyses between polymorphisms in the GJA4 gene cluster and
      myocardial infarction in Japanese.

PMID- 14652666
TI  - Role of p22phox in angiotensin II and platelet-derived growth factor AA induced
      activator protein 1 activation in vascular smooth muscle cells.
AB  - Reactive oxygen species (ROS) are involved in the transcriptional response to
      angiotensin (ANG) II. In this setting the role of NAD(P)H oxidase, an important
      source of ROS as second messengers, is not completely understood. In particular
      in human cells detailed insights into this mechanism are lacking. We investigated
      the role of ANG II and platelet-derived growth factor (PDGF) AA induced ROS
      generation derived from p22phox-containing NAD(P)H oxidase in the activation of
      activator protein (AP) 1 in human vascular smooth muscle cells (SMCs). Both ANG
      II and PDGF AA induced ROS generation in SMCs which was angiotensin type 1
      receptor and PDGF alpha receptor dependent. Specific inhibition of the p22phox
      subunit of the NAD(P)H oxidase using either p22phox neutralizing antibody or
      p22phox antisense oligodeoxynucleotides (ODNs) attenuated both ANG II and PDGF AA
      induced ROS generation. Furthermore, PDGF AA but not ANG II induced p22phox mRNA
      expression. ANG II and PDGF AA both activated the redox-sensitive transcription
      factor AP-1, which was inhibited by p22phox antisense ODNs. These findings
      demonstrate that AP-1 activation in human SMCs in response to ANG II and PDGF AA
      is mediated via generation of p22phox-dependent ROS. This highlights the crucial
      role of the p22phox-containing NAD(P)H oxidase in the ANG II and PDGF AA induced
      signal transduction pathway.

PMID- 14652668
TI  - Endogenous markers of tumor hypoxia predictors of clinical radiation resistance?
AB  - BACKGROUND: Eppendorf electrode measurements of tumor oxygenation have defined an
      adverse effect of tumor hypoxia on prognosis after radiotherapy and other
      treatment modalities, in particular in head and neck and cervix carcinomas as
      well as soft tissue sarcomas. Recently, the immunohistochemical detection of
      proteins involved in the "hypoxic response" of tumor cells has been discussed as
      a method to estimate hypoxia in clinical tumor specimens. MATERIAL AND METHODS:
      This review focuses on clinical and experimental data, regarding prognostic
      impact and comparability with other methods of hypoxia detection, for three
      proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible
      factor-1alpha(HIF-1alpha), carbonic anhydrase 9 (CA 9), and glucose transporter 1
      (GLUT1). RESULTS: None of the three potential hypoxia markers is exclusively
      hypoxia-specific, and in each case protein can be detected under normoxic
      conditions in vitro. HIF-1alpha responds rapidly to hypoxia but also to
      reoxygenation, making this marker quite unstable in the context of clinical
      sample collection. The perinecrotic labeling pattern typical of chronic hypoxia
      and a reasonable agreement with injectable hypoxia markers such as pimonidazole
      have most consistently been described for CA 9. All three markers showed
      correlation with Eppendorf electrode measurements of tumor oxygenation in
      carcinoma of the cervix. In nine of 13 reports, among them all three that refer
      to curative radiotherapy for head and neck cancer, HIF-1alpha overexpression was
      associated with poor outcome. CA 9 was an adverse prognostic factor in cervix,
      head and neck and lung cancer, but not in two other head and neck cancer reports.
      GLUT1 predicted for poor survival in colorectal, cervix and lung cancer.
      CONCLUSION: Endogenous markers have the potential to indicate therapeutically
      relevant levels of hypoxia within tumors. Clinical trials assessing a marker's
      ability to predict a benefit from specific hypoxia-directed treatment (e. g.,
      tirapazamine, "ARCON" concept) are necessary to define the potential of
      individual markers.

PMID- 14652667
TI  - Peptides containing antigenic and cationic domains have enhanced, multivalent
      immunogenicity when bound to DNA vaccines.
AB  - We explored strategies to codeliver DNA- and peptide-based vaccines in a way that
      enhances the immunogenicity of both components of the combination vaccine for T
      cells. Specific CD8(+) T cell responses to an antigenic peptide are primed when
      the peptide is fused to a cationic peptide domain that is bound to plasmid DNA or
      oligonucleotides (ODN; with or without CpG motifs). Plasmid DNA mixed with
      antigenic/cationic peptides or histones forms large complexes with different
      biological properties depending on the molar ratios of peptide/protein and
      polynucleotide. Complexes containing high (but not low) molar ratios of cationic
      peptide to DNA facilitate transfection (DNA uptake and expression of the plasmid
      encoded product) of cells. In contrast, complexes containing low (but not high)
      molar ratios of cationic peptide to DNA prime potent multispecific T cell
      responses after a single intramuscular injection of the complexes. The general
      validity of this observation was confirmed mixing different antigenic/cationic
      peptides with different DNA vaccines. In these vaccine formulations,
      multispecific CD8(+) T cell responses specific for epitopes of the peptide- as
      well as the DNA-based vaccine were efficiently coprimed, together with humoral
      antibody responses to conformational determinants of large viral antigens encoded
      by the DNA vaccine. The data indicate that mixtures of DNA vaccines with
      antigenic, cationic peptides are immunogenic vaccine formulations particularly
      suited for the induction of multispecific T cell responses.

PMID- 14652669
TI  - Low-dose irradiation and short-exposure suboptimal-dose paclitaxel adversely
      modulate metastatic potential of squamous carcinoma cells.
AB  - BACKGROUND AND PURPOSE: Low-dose irradiation and suboptimal drug concentrations
      may induce unexpected biological responses. Paclitaxel (PTX) is a widely used
      drug, which has a range of antitumoral effects and which is also regarded as a
      radiation sensitizer. In this study, it was tested how "suboptimal" short
      exposure to PTX modifies the biological effects of low-dose irradiation on human
      epithelial carcinoma cell lines. MATERIAL AND METHODS: 2 Gy irradiation, 7 and
      100 nM PTX treatment, and their combinations were tested on squamous and
      transitional cell carcinoma lines A431, KB and ECV304. Cytoskeleton of interphase
      cells was investigated with immunocytochemistry and confocal laser scanning
      microscopy; viability and clonogenicity were assessed with MTT test and standard
      clonogenic assay. Effects on tumor growth and metastatic potential of A431 cells
      were tested in vivo using a liver metastasis model in SCID mice. RESULTS:
      Exposure of human tumor cells to irradiation induced bundling of microtubules,
      similar to PTX. Combined treatments suspended each other's effect independently
      of treatment combinations. Single or combination treatments with low-dose PTX did
      affect cell proliferation to no relevant extent in vitro or in vivo (primary
      tumor xenografts of A431 cells). However, exposure to irradiation of A431 cells
      inhibited while 100 nM PTX stimulated their liver-metastatic potential.
      Combination of 100 nM PTX with irradiation suspended the effect of 100 nM PTX and
      exhibited the highest antimetastatic activity. CONCLUSION: Short exposure to PTX
      and irradiation can interfere with each other's effects on tumor cells without
      significant modulation of proliferation and tumorigenicity. However, PTX and
      irradiation may significantly modulate the metastatic property of tumor cells.

PMID- 14652670
TI  - Differentiation between recurrent tumor and radiation necrosis in a child with
      anaplastic ependymoma after chemotherapy and radiation therapy.
AB  - BACKGROUND: In patients after treatment for malignant brain tumors, a clear
      distinction between tumor recurrence and radiation necrosis can be challenging.
      This case report describes the diagnostic workup in a child with anaplastic
      ependymoma and inconclusive MRI (magnetic resonance imaging) and PET (positron
      emission tomography) findings. CASE REPORT: 1.5 years after resection,
      hyperfractionated radiotherapy and chemotherapy of an anaplastic ependymoma in
      the right parietal region, the cranial MRI of an 11-year-old girl showed multiple
      small contrast-enhanced lesions in the frontal cortex. In the following months,
      these lesions increased in number and size and neurologic symptoms developed.
      Diagnostic workup included repeated MRI scans, PET with an (18)F-amino acid and
      (18)F-fluorodeoxyglucose (FDG), as well as a brain biopsy. RESULTS: Amino acid
      PET, performed when the lesions were still small, showed multiple small areas of
      mild uptake in close correlation to the MRI lesions. Although not typical, this
      result was suspicious of tumor seeding, the more since the lesions appeared in
      gray matter areas outside the high-dose-rate irradiation field. A biopsy,
      performed 6 months later when the clinical appearance worsened, showed no tumor
      tissue. FDG PET, performed after the size and number of the lesions had
      increased, showed no intensely increased glucose metabolism, a high-grade
      recurrent tumor was therefore very unlikely. In the following months, the
      clinical picture stabilized. CONCLUSION: The final interpretation of the lesions
      was multiple focal radiation necrosis based on perfusion abnormalities after
      chemotherapy and conformal hyperfractionated radiotherapy, probably due to an
      individually enhanced vulnerability of the cerebral vessels.

PMID- 14652671
TI  - Concurrent radiochemotherapy with vinorelbine plus cisplatin or carboplatin in
      patients with locally advanced non-small-cell lung cancer (NSCLC) and an
      increased risk of treatment complications. Preliminary results.
AB  - BACKGROUND: In elderly patients, patients with multiple morbidities, and patients
      with a reduced general condition, the standard treatment of inoperable non-small
      cell lung cancer (NSCLC) consists of either chemotherapy or radiation therapy
      alone and is associated with an extremely poor prognosis. We therefore
      investigated the feasibility, toxicity, and efficacy of radiotherapy with
      concurrent chemotherapy using vinorelbine plus cisplatin or carboplatin in NSCLC
      patients at risk for treatment complications. PATIENTS AND METHODS: A total of 33
      patients (six women, 27 men, median age 65 years) with locally advanced,
      functionally inoperable pulmonary carcinomas, recurrent lung cancer or
      postoperative macroscopic residual tumors (R2) with an increased risk of
      treatment complications (WHO performance status 2/3; cardiac, renal or pulmonary
      failure; marked pretherapeutic weight loss; age between 71-75 years) received
      12.5 mg of vinorelbine per m(2) body surface area (BSA) on days 1, 8, 15, 29, 36
      and 43 plus either cisplatin 20 mg/m(2) BSA (ten patients) or carboplatin 70
      mg/m(2) BSA (23 patients) on days 1-5 and 29-33 together with conventionally
      fractionated radiotherapy. The tumor regions were irradiated with doses of up to
      63 Gy (90% isodose), and potentially affected lymph nodes received doses of up to
      45.0 or 50.4 Gy (90% isodose). RESULTS: Briefly, 31 of 33 patients successfully
      completed radiation therapy and 26 received four cycles of vinorelbine plus at
      least two cycles of cisplatin or carboplatin. Hematotoxic side effects included
      grade III leukocytopenia (n = 8), grade III thrombocytopenia (n = 5), and grade
      IV thrombocytopenia (n = 2). Other side effects consisted of peripheral
      neuropathy grade III (n = 1) and esophagitis grade IV (n = 1). Severe pneumonitis
      did not occur. Six patients had pneumonia before radiochemotherapy. 21 patients
      (63%) exhibited a complete (n = 7) or partial response (n = 14) to
      chemoradiation. The twelve nonresponders had either stable (n = 9) or progressive
      disease (n = 3). The survival rates plus standard deviations were as follows: 1
      year survival: 60 +/- 8%, 2-year survival: 36 +/- 9%, 3-year survival: 24 +/- 9%,
      median survival time: 17 months (5;29 months; 95% confidence interval [CI]),
      median progression-free survival: 11 months (9;13 months; 95% CI). The median
      follow-up time was 14 months. CONCLUSION: Conventionally fractionated
      radiochemotherapy with vinorelbine plus a platinum derivative is feasible in
      patients with NSCLC and increased risk of treatment complications. Compared to
      patient populations described in the literature, the survival rates achieved by
      concurrent radiochemotherapy appear to be better than those achieved with
      radiotherapy alone.

PMID- 14652672
TI  - Acute toxicity of adjuvant radiotherapy in locally advanced differentiated
      thyroid carcinoma. First results of the multicenter study differentiated thyroid
      carcinoma (MSDS).
AB  - BACKGROUND AND PURPOSE: The indication for adjuvant postoperative radiotherapy in
      patients with differentiated thyroid carcinoma (DTC) extending beyond the thyroid
      capsule has been an issue of controversy during the past 2 decades. No randomized
      studies evaluating the benefit of radiotherapy have been published so far. In the
      Multicenter Study Differentiated Thyroid Carcinoma (MSDS), a randomization has
      been performed concerning external-beam radiotherapy in patients with DTC
      extending beyond the thyroid capsule (pT4 pN0/1/x cM0, TNM classification, 5th
      edition, 1997) following surgery and radioiodine therapy. Radiation-associated
      toxicity has been prospectively evaluated. PATIENTS AND METHODS: Radiotherapy was
      performed with 50.4 Gy (pN0) or 54.0 Gy (pN1/x) to the cervical, supraclavicular
      and upper mediastinal lymph nodes. A total dose of 59.4 Gy (R0 resection) or 66.6
      Gy (R1) was used to treat the tumor bed. Conventional fractionation was used with
      1.8 Gy/d. At the time of the analysis, 36 patients were randomized or allocated
      to treatment arm A (with external-beam radiotherapy). Of these, 22 were treated
      with radiotherapy, and documentation of acute toxicity was available. Toxicity
      was evaluated prospectively according to the RTOG/EORTC criteria. RESULTS: The
      maximal acute toxicity observed during radiotherapy was grade I in four patients,
      grade II in 16 patients, and grade III in two patients (9.1%; 95% confidence
      interval [95% CI] 1.1-29.2%). Toxicity was mainly observed at the pharynx,
      larynx, and skin. In 19 patients, residual toxicity within 100 days following
      radiotherapy was evaluated. No residual toxicity was observed in two patients.
      Maximal residual toxicity was grade I in 13 patients and grade II in four. No
      further grade III toxicity could be observed. CONCLUSION: The majority of
      patients experience mild to moderate side effects from adjuvant external-beam
      radiotherapy. At the first follow-up examination, most side effects have
      subsided. Acute toxicity is tolerable in these patients.

PMID- 14652673
TI  - [Follicle centre lymphoma: treatment results for stage I and II].
AB  - PURPOSE: Radiotherapy is a curative treatment modality in the early stages of
      follicle centre lymphoma. Survival rates, patterns of failure and prognostic
      factors were evaluated in a retrospective analysis. PATIENTS AND METHODS: 116
      patients with follicle centre lymphoma stage I and II were treated between 1970
      and 1999 in Dresden. Therapy modalities were radiotherapy alone (103 patients) or
      combined radiotherapy/chemotherapy (13 patients). Radiotherapy was applied as
      involved-field-(IFI)- (104 patients), extended-field- (nine patients) or total
      nodal- (three patients) irradiation. Patients received doses between 25 Gy and 50
      Gy (median 35 Gy). RESULTS: The 5- and 10-year actuarial overall survival rates
      were 76% and 51%. Relapse free survival was 62% and 48% respectively. The median
      follow-up was 4,0 years. Relapses after complete remission were registered in 44
      cases. Six patients have had in-field-recurrences. The majority of out-field
      recurrences were nodal relapses (50%). 11% of relapses occurred outside of lymph
      nodes or were disseminated failures (18%). Significant favorable prognostic
      factors identified by multivariate and univariate analysis were low age (age < 50
      years vs. age > 50 years), low stage and performance of bipedal lymphangiography
      as primary staging procedure. CONCLUSIONS: Radiotherapy is an effective and
      tolerable treatment modality for follicle centre lymphoma in the early stages I
      and II. We registered a high proportion of nodal recurrences, which may be
      minimized by prophylactic extended radiotherapy.

PMID- 14652675
TI  - Effects of radiation treatment planning and patient fixation on the results of
      postoperative radiotherapy of childhood medulloblastoma.
AB  - PURPOSE: To assess the prognostic factors and the benefit of introducing head
      fixation and CT-assisted radiation treatment planning following postoperative
      radiotherapy in 83 children with medulloblastoma. PATIENTS AND METHODS: In 24
      children treated between 1986 and 1994, no head fixation was applied and boost
      irradiation was not based on individual radiation treatment planning. Since 1995,
      boost irradiation has been assisted by CT-based individual radiation treatment
      planning and ORFIT head fixation in 59 patients. The influence of various factors
      including age, sex, tumor location, extent, type of surgery, risk group,
      radiation dose to posterior fossa and spinal axis, and the effect of head
      fixation and CT-assisted radiation treatment planning on 5-year relapse-free and
      5-year overall survival was investigated. RESULTS: Overall and relapse-free
      survival rates for all 83 patients were 73.5% and 60.7%. Univariate analysis
      identified metastatic disease (p = 0.034) and the application of head fixation
      and individual radiation treatment planning (p = 0.013) as significant prognostic
      factors for overall survival. Relapse-free survival rates were influenced by
      metastatic disease (p = 0.028) and the application of head fixation and
      individual radiation treatment planning (p = 0.009). On multivariate analysis,
      metastatic disease (p = 0.04) and the application of head fixation and individual
      radiation treatment planning (p = 0.045) were significant factors for overall and
      relapse-free survival (p = 0.036 and p = 0.041) as well. CONCLUSION: Metastatic
      disease appears to be correlated with a worse prognosis in this analysis.
      Individual radiation treatment planning and head fixation have a positive impact
      on survival. For postoperative radiotherapy of the posterior fossa, the
      application of head fixation and individual CT-based radiation treatment planning
      is considered indispensable in each case.

PMID- 14652676
TI  - Inflammation research Lifetime Achievement Award 2003, presented to Derek A.
      Willoughby.

PMID- 14652674
TI  - [Radiation therapy for Morbus Ledderhose -- indication and clinical results].
AB  - BACKGROUND: Morbus Ledderhose (ML) is a rare hyperproliferative disorder of the
      plantar aponeurosis which is similar in its clinical course to Morbus Dupuytren
      (MD). We examined whether radiotherapy (RT) can effect symptoms and prevent
      disease progression. PATIENTS AND METHODS: From June 1996 to December 2001, 25
      patients (12 female/13 male) aged 9-76 (median: 56) years had radiotherapy (RT)
      for symptomatic ML. Follow-up (FU) was at least 1 year. 36 feet (16 right/20
      left) were treated, as eleven patients had bilateral disease. Twelve (48%)
      patients had MD. There were 63 nodules (with 0,5-6,5 cm diameter) on all feet and
      20 cords (with 1-4 cm length) on 13 (52%) feet prior to RT. 21 (84%) patients had
      one or more signs: 14 (56%) severe local pain, eight (32%) walking difficulties,
      twelve (48%) other symptoms, pressure or tension sensation. The RT field involved
      all nodules and cords plus safety margin. Two RT-series were applied (each 5 3 Gy
      in 1 week) separated by 8-12 weeks up to a total dose of 30 Gy. Evaluation was
      performed at the end of RT, after 3 and 12 months FU and in December 2002. The
      primary endpoint was prevention of disease progression and avoidance of surgery.
      Secondary endpoints were objective changes of morphological and functional
      parameters and patient's satisfaction measured on a visual analogue scale (VAS).
      RESULTS: With a median FU of 38 (12-67) months no patient experienced progression
      or underwent surgery: 11 of 36 (44%) feet had a reduced number (overall: -16) or
      size of nodules, 7 of 13 (54%) feet had a reduced number (overall: -9) or length
      of cords; gait was improved in six of twelve (50%) feet; pain was reduced or had
      completely disappeared in 9 of 15 (60%) feet, and other symptoms disappeared in 8
      of 18 (44%) symptomatic feet. 20 (80%) patients regarded 28 of 36 (78%) treated
      feet as improved and 8 (22%) in stable condition. The median relative improvement
      stated by patients on the VAS was 50% (0-100%). Treatment side effects were
      minimal: During and within 3 months of the RT course only a slight erythema (CTC
      1 degrees ) was seen in five treated lesions, while dry skin changes within the
      RT portal were observed in three cases (11%) in long term FU (> 12 months).
      CONCLUSIONS: Radiotherapy is effective in treating ML and may prevent otherwise
      necessary surgical interventions. Nodules, cords and symptoms regress, but long
      term outcome of at least 5 years has to be awaited. Prospective phase III studies
      should confirm these results.

PMID- 14652678
TI  - Heat shock proteins (HSP) for immunotherapy of rheumatoid arthritis (RA).
AB  - Rheumatoid arthritis (RA) is an inflammatory disease that primarily involves the
      joints and has a worldwide prevalence of about one percent, with a female to male
      ratio of 3:1. This chapter summarizes some of the recent progress in molecular
      immunology, and discusses the application of this new knowledge for therapeutic
      purposes. We focus on our recent experiences and that of others in modulation of
      antigen specific responses as a tool for manipulating autoimmune inflammation.
      Particular emphasis is given to the concept of exploiting for therapeutic
      purposes a natural mechanism of immune regulation. This mechanism is based on
      sequential cross recognition of bacterial and human derived heat shock protein
      peptides.

PMID- 14652679
TI  - A comparison of the anti-inflammatory activities of conjugated estrogens and 17
      beta estradiol.
AB  - OBJECTIVE AND DESIGN: Unregulated chronic inflammatory process partly due to an
      estrogen deficiency may render postmenopausal women vulnerable to degenerative
      conditions such as arthritis, osteoporosis, atherosclerosis, and Alzheimer's
      disease. Current confusion regarding therapeutic efficacy of estrogen replacement
      therapy may be due to different estrogen formulations used, short term therapy,
      as well as advanced stage of the disease. MATERIALS AND METHODS: We compared anti
      inflammatory activities of two major estrogen preparations, conjugated equine
      estrogen (CEE) and 17-beta estradiol, using an animal model (rat mesentery) of in
      vivo inflammatory reaction to intravenously infused amyloid-beta, examined by
      video recording and subsequently analyzed by transmission electron microscopy.
      Cellular markers of inflammation were monitored: leukocyte migration, platelet
      activation, mast cell activation/degranulation, and endothelial disruption.
      RESULTS: Low doses of CEE (0.3 mg/kg for 3 weeks) demonstrated significant anti
      inflammatory activity, whereas even at high doses (2.0 mg) 17-beta estradiol had
      only minimal activity. CONCLUSION: CEE, a mixture of several compounds, may have
      some component(s) with significant anti-inflammatory activity. The anti
      inflammatory activity of CEE may have a role in prevention of several
      degenerative diseases associated with menopause.

PMID- 14652680
TI  - Effects of water-soluble cigarette smoke extracts upon the release of beta
      hexosaminidase from RBL-2H3 basophilic leukaemia cells in response to substance
      P, compound 48/80, concanavalin A and antigen stimulation.
AB  - OBJECTIVE AND DESIGN: To determine whether water-soluble constituents of
      cigarette smoke affect mast cell function using an in vitro model, RBL-2H3
      basophilic leukaemia cells. MATERIALS AND METHODS: RBL-2H3 cells were induced to
      degranulate in response to compound 48/80 and substance P, as assessed by
      monitoring the release of the granular enzyme beta-hexosaminidase, by treatment
      for 7 days with 20 microM quercetin. Responses to concanavalin A and antigen were
      determined by measuring the beta-hexosaminidase release from cells cultured on
      fibronectin-coated plates. RESULTS: The beta-hexosaminidase release response to
      compound 48/80 induced by quercetin treatment was accompanied by a release of
      lactate dehydrogenase, suggesting that degranulation is not the only process
      triggered by compound 48/80 under these conditions. Quercetin treatment reduced
      the beta-hexosaminidase release response to concanavalin A. Precoating of the
      culture wells with rat fibronectin enhanced the beta-hexosaminidase response to
      calcimycin, but not to concanavalin A. Under these conditions, concanavalin A did
      not induce a release of lactate dehydrogenase. The responses to c48/80, substance
      P, calcimycin, concanavalin A and antigen (after IgE pretreatment) were reduced
      by treatment with cigarette smoke solution obtained from standard and low-tar
      cigarettes (IR3 and IR5F). The effect of cigarette smoke solution from IR5F
      cigarettes upon the beta-hexosaminidase release elicited by compound 48/80 (in
      quercetin-treated cells) and by concanavalin A (in cells cultured on fibronectin
      coated wells) could be prevented by N-acetyl-L-cysteine, but not with either
      hemoglobin, alpha-tocopherol, catalase or palmitoylethanolamide. N-acetyl-L
      cysteine also reduced the effect of cigarette smoke solution upon the
      degranulation response to antigen. CONCLUSIONS: Under the conditions used,
      oxidants present in cigarette smoke solution from IR5F cigarettes reduce the
      ability of RBL-2H3 cells to degranulate in response to both immunological and non
      immunological stimuli.

PMID- 14652681
TI  - Impairment of inflammatory response in adult rats submitted to maternal
      undernutrition during early lactation: role of insulin and glucocorticoid.
AB  - OBJECTIVE: Early nutritional environment may program permanent metabolic
      alterations, predisposing to later diseases. We have investigated the
      interference of maternal malnutrition during lactation with the development of
      acute inflammation in adult rats. MATERIALS AND METHODS: Adult rats, offspring of
      dams fed with either protein-free diet (UN group) or 22% protein diet (C group)
      during the first 10 days of lactation, were submitted to pleurisy with
      carrageenan (500 microg/cavity). Pleural edema, neutrophil migration and ICAM
      expression, were evaluated 4 h after and correlated with alterations in plasma
      insulin and corticosterone. Leukocyte-endothelium interactions were evaluated by
      intravital microscopy 1 h after inflammation. RESULTS: Compared to controls, UN
      rats showed a decrease in pleural edema formation (50%), neutrophil migration
      (50%), endothelial ICAM-1 expression on pulmonary tissue, and impairment in
      leukocyte adhesion (50%) and migration (80%) through endothelium. Circulating
      insulin was lower (42%) and corticosterone was higher (34%) in UN, compared to
      controls. Pre-treatment of UN with insulin (5 IU/day) or RU486 (20 mg/kg/day),
      inhibitor of glucocorticoid receptor, restored leukocyte functions and ICAM-1
      expression. CONCLUSION: Postnatal maternal malnutrition, programming for
      permanent alterations in insulin and glucocorticoid secretion in progeny, that
      were unable to properly mount an inflammatory response, probably predisposes to
      chronic diseases in adult life.

PMID- 14652682
TI  - Platelet activity measured by plasma levels of beta-thromboglobulin and platelet
      factor 4 in seasonal allergic rhinitis during natural pollen exposure.
AB  - BACKGROUND: Upon activation, platelets release mediators with potent inflammatory
      properties in IgE-mediated immune responses. Moreover, the atopic state leads
      towards functional abnormalities of these cells. OBJECTIVE: The aim of our study
      was to examine the degree of activation of circulating platelets in patients with
      seasonal allergic rhinitis (SAR) during the symptomatic period, to improve the
      understanding of platelet function in atopy. SUBJECTS AND METHOD: Plasma levels
      of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) - specific markers
      of platelet activation were measured by enzyme-linked immunoassay in 20 patients
      suffering from SAR and in 15 healthy, nonatopic subjects. RESULTS: There were no
      significant differences in peripheral blood platelet numbers and plasma levels of
      beta-TG and PF4 in SAR patients when compared with control subjects. CONCLUSION:
      It seems that increased in vivo platelet activity, assessed by measuring plasma
      beta-TG and PF4, may not occur during allergic inflammation that is associated
      with SAR.

PMID- 14652683
TI  - Effect of hypoxia on monocyte chemotactic protein-1 (MCP-1) gene expression
      induced by Interleukin-1beta in human synovial fibroblasts.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) synovial membrane is characterized by
      leucocyte infiltration and secretion of chemotactic and proinflammatory factors.
      Since hypoxia is an important pathogenic factor in inflamed synovium, we examined
      the effects of hypoxia on monocyte chemotactic protein-1 (MCP-1) expression in
      human rheumatoid arthritis synovial fibroblasts (RASF) under IL-1beta-stimulated
      and -unstimulated conditions. METHODS: Synovial fibroblasts were isolated from
      RA, osteoarthritis (OA) and healthy knee joints and subjected to hypoxia or/and
      IL-1beta treatment. MCP-1 expression and protein secretion were measured by real
      time PCR and ELISA, respectively. RESULTS: Hypoxia reduces MCP-1 expression and
      protein secretion in RASF. The same response to hypoxia was found in OA and
      healthy SF cultures. Treatment with actinomycin D showed that hypoxic down
      regulation of MCP-1 expression was due to a decrease in transcription, since the
      half-life of MCP-1 mRNA was unchanged. A cycloheximide study demonstrated that de
      novo protein synthesis was not required for the hypoxic effect. The decrease in
      MCP-1 expression by hypoxia was mimicked by cobalt chloride in unstimulated RASF
      with no effect on IL-1beta-activated MCP-1, suggesting differences in the
      signaling mechanisms. The analysis of IkappaB degradation and NF-kappaB
      translocation revealed that hypoxia did not affect IL-1beta activation of NF
      kappaB. CONCLUSION: Hypoxia regulates MCP-1 expression under both basal and
      cytokine-stimulated conditions, suggesting that reduced oxygen supply is an
      important factor that mediates chemotaxis of monocytes to the area of
      inflammation.

PMID- 14652684
TI  - Detecting tau isoforms in archival cases.

PMID- 14652685
TI  - The modernization of pediatric neurosurgery. The Donald D. Matson Lecture 2003.
AB  - INTRODUCTION: It might be presumed that the discipline of pediatric neurosurgery
      is as youthful as the patients it serves. But this subspecialty of neurosurgery
      is at least 50 years old. DISCUSSION: This 2003 Donald D. Matson Memorial Lecture
      will examine the growth and development of children's neurosurgical care from the
      aspects of its identity and continuing educational activity, the impact of
      technology, outcome measures, and the role of public advocacy.

PMID- 14652686
TI  - Intracranial hemorrhage following blunt injury to a shunt valve.
AB  - CASE REPORT: The authors report a case of a child who sustained blunt injury to a
      shunt valve during a basketball game, which resulted in an intracranial
      hemorrhage. CONCLUSION: This occurrence, although rare, reinforces the
      recommendation for protective headgear when patients with shunts engage in
      activities that may result in direct impact to the head.

PMID- 14652687
TI  - Fatty acid esterification in the yolk sac membrane of the avian embryo.
AB  - The transfer of lipid from the yolk to the avian embryo is mediated by the yolk
      sac membrane (YSM). Some, but not all, of the published morphological evidence
      supports the view that the lipid undergoes a cycle of hydrolysis and re
      esterification during translocation across the YSM. The present study aims to
      test this view by investigating the capacity of the YSM to perform esterification
      of free fatty acids to form acyl-lipids. YSM pieces (area vasculosa), obtained
      from the chicken embryo at day 10 of development, were incubated in vitro in
      medium containing [14C]-palmitic acid. Radioactivity was rapidly incorporated
      into the tissue lipid indicating a high capacity for esterification. The
      incorporation was linear with time during the 1-h incubation. Approximately 84%
      of the incorporated label was recovered in triacylglycerol, 12% was incorporated
      into phospholipid and less than 1% was detected in cholesteryl ester. [14C]
      palmitic acid was incorporated primarily at the sn-1/3 positions in the
      triacylglycerol molecule and at the sn-1 position of phospholipid. The
      incorporation of label into tissue pieces obtained from the non-vascularized
      peripheral region of the YSM (area vitellina) was much more limited than that
      observed for the area vasculosa. The results support the hypothesis that yolk
      lipid is hydrolyzed and re-esterified during transfer across the YSM.

PMID- 14652688
TI  - Biological significance of distinguishing between similar colours in spectrally
      variable illumination: bumblebees (Bombus terrestris) as a case study.
AB  - Individual bumblebees were trained to choose between rewarded target flowers and
      non-rewarded distractor flowers in a controlled illumination laboratory. Bees
      learnt to discriminate similar colours, but with smaller colour distances the
      frequency of errors increased. This indicates that pollen transfer might occur
      between flowers with similar colours, even if these colours are distinguishable.
      The effect of similar colours on reducing foraging accuracy of bees is evident
      for colour distances high above discrimination threshold, which explains previous
      field observations showing that bees do not exhibit complete flower constancy
      unless flower colour between species is distinct. Bees tested in spectrally
      different illumination conditions experienced a significant decrease in their
      ability to discriminate between similar colours. The extent to which this happens
      differs in different areas of colour space, which is consistent with a von Kries
      type model of colour constancy. We find that it would be beneficial for plant
      species to have highly distinctive colour signals to overcome limitations on the
      bees performance in reliably judging differences between similar colours. An
      exception to this finding was flowers that varied in shape, in which case bees
      used this cue to compensate for inaccuracies of colour vision.

PMID- 14652689
TI  - Expression of a novel yeast gene that detoxifies the proline analog azetidine-2
      carboxylate confers resistance during tobacco seed germination, callus and shoot
      formation.
AB  - A novel acetyltransferase (Mpr1) found in Saccharomyces cerevisiae (strain
      Sigma1278b) has been shown to specifically detoxify a proline analog, l-azetidine
      2-carboxylic acid (A2C) in yeast cells [M. Shichiri et al. (2001) J Biol Chem
      276: 41998-42002]. We investigated whether the yeast MPR1 gene would function
      similarly in a plant system and if its expression could confer resistance to
      proline analogs. The MPR1 gene coding sequence driven by two different
      constitutive promoters, with or without the 5'- and 3'-noncoding sequence from
      the MPR1 gene adjacent to the conventional NOS terminator, was transformed into
      tobacco ( Nicotiana tabacum L. cv. Xanthi) plants via Agrobacterium tumefaciens
      infection. The presence of the yeast 5'- and 3'-noncoding sequences appeared to
      increase the likelihood of MPR1 gene expression in the transgenic plants. The
      kanamycin-selected transgenic plants with a high level of Mpr1 activity grew
      normally, and their progeny expressed acetyltransferase activity that could
      utilize A2C, azetidine-3-carboxylic acid and 4-hydroxy- l-proline as substrates.
      Resistance to A2C, but not to the other two analogs, was exhibited during leaf
      tissue culture and seed germination. The A2C toxicity to the wild-type plants was
      reversed by the addition of proline, suggesting that A2C acts as a proline
      analog. Our studies confirm that MPR1 can function in a similar fashion in
      tobacco as in yeast to detoxify the toxic proline analog A2C, so it could
      potentially be used as a new selectable marker for plant transformation. However,
      our attempts to utilize MPR1 as an efficient selectable marker gene for the A.
      tumefaciens-mediated transformation of tobacco were unsuccessful.

PMID- 14652690
TI  - Sacral inflammatory pseudotumor revealed by paraneoplastic syndrome.
AB  - There is still debate on whether inflammatory pseudotumor should be considered
      benign or malignant. This lesion has only been reported twice in bone, apart from
      cases complicating foreign body reaction to joint replacement arthroplasty. We
      report here a third case, localized at the sacrum. A 31-year-old man had
      inflammatory dorsalgia and polyarthralgia without synovitis but with fever,
      asthenia, and erythema nodosa. Biological tests and X-rays were not informative,
      but technetium scintigraphy revealed a high level of left sacroiliac tracer
      binding. Several nonsteroidal anti-inflammatory drugs and sulfasalazine treatment
      were given over 3 months but ineffective. Pelvic magnetic resonance imaging
      showed an osteolytic tumor of the sacrum. Biopsy suggested a malignant
      fibrosarcoma, but complete evaluation after surgical resection demonstrated an
      inflammatory pseudotumor. All clinical symptoms disappeared within a few days
      after surgery, which is suggestive of a paraneoplastic syndrome. No relapse has
      occurred after 4 years.

PMID- 14652692
TI  - Mapping of sporulation-specific functions in the yeast syntaxin gene SSO1.
AB  - The yeast Saccharomyces cerevisiae has two closely related plasma membrane
      syntaxins, Sso1p and Sso2p, which together provide an essential function in
      vegetative cells. However, Sso1p is also specifically needed during sporulation;
      and this function cannot be provided by Sso2p. We used fusions between SSO1 and
      SSO2 to map the sporulation-specific function of SSO1. We found that the two N
      terminal alpha-helices Ha and Hb of Sso1p are important for sporulation, since it
      is reduced 8-fold for fusions where Ha and Hb are derived from Sso2p. In
      contrast, the C-terminal half of Sso1p does not seem to be specifically required
      for sporulation. Surprisingly, we further found that the 3' untranslated region
      (3'UTR) of SSO1 is essential for sporulation. Western blots failed to reveal a
      preferential expression of Sso1p in sporulating cells, indicating that effects on
      gene expression are unlikely to explain why the SSO1 3'UTR is needed for
      sporulation.

PMID- 14652693
TI  - NADH-reductive stress in Saccharomyces cerevisiae induces the expression of the
      minor isoform of glyceraldehyde-3-phosphate dehydrogenase (TDH1).
AB  - A strain of Saccharomyces cerevisiae lacking the GPD2 gene, encoding one of the
      glycerol-3-phosphate dehydrogenases, grows slowly under anaerobic conditions, due
      to reductive stress caused by the accumulation of cytoplasmic NADH. We used 2D
      PAGE to study the effect on global protein expression of reductive stress in the
      anaerobically grown gpd2Delta strain. The most striking response was a strongly
      elevated expression of Tdh1p, the minor isoform of glyceraldehyde-3-phosphate
      dehydrogenase. This increased expression could be reversed by the addition of
      acetoin, a NADH-specific redox sink, which furthermore largely restored anaerobic
      growth of the gpd2Delta strain. Additional deletion of the TDH1 gene (but not of
      TDH2 or TDH3) improved anaerobic growth of the gpd2Delta strain. We therefore
      propose that TDH1 has properties not displayed by the other TDH isogenes and that
      its expression is regulated by reductive stress caused by an excess of
      cytoplasmic NADH.

PMID- 14652694
TI  - Fungal proteomics: mapping the mitochondrial proteins of a Trichoderma harzianum
      strain applied for biological control.
AB  - Mitochondria are essential for cellular functions across organisms. A proteomic
      approach was taken to separate and identify mitochondrial proteins from a strain
      of Trichoderma harzianum with well established biocontrol properties. We
      optimized a method for the preparation of a sample enriched with mitochondria by
      ensuring efficient cell lysis and including several washing steps to minimize
      cytoplasmic contamination. We separated hundreds of proteins, using two
      dimensional gel electrophoresis and identified 31 protein spots from T.
      harzianum, using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry and liquid chromatrography with mass spectrometry. Over 50% of the
      identified proteins were known to localize in the mitochondria. Three protein
      spots were identified from T. harzianum and a further five protein spots from the
      genera Trichoderma and Hypocrea. The remaining protein spots were identified by
      cross-species identification from other filamentous fungi, including Neurospora
      crassa and Aspergillus spp, and yeasts, including Saccharomyces cerevisiae and
      Schizosaccharomyces pombe. In total, we identified 25 protein spots from T.
      harzianum, representing proteins that have not been characterized in existing
      Trichoderma protein databases. To our knowledge, this is the first two
      dimensional mitochondrial protein map of a filamentous fungus.

PMID- 14652691
TI  - A genome's-eye view of the light-harvesting polypeptides of Chlamydomonas
      reinhardtii.
AB  - Chlamydomonas reinhardtii is a valuable model system for defining the structure
      and function of polypeptides of the photosynthetic apparatus and the dynamic
      aspects of photosynthesis. Recently, a genome-wide analysis of cDNAs and a draft
      genome sequence that covers approximately 90% of the genome were made available,
      providing a clear picture of the composition of specific gene families, the
      relationships among the gene family members, and the location of each member on
      the genome. We used the available sequence information to analyze the extensive
      family of light-harvesting genes in C. reinhardtii. There are nine genes encoding
      polypeptides of the major light-harvesting complex of photosystem II, two genes
      encoding the minor light-harvesting polypeptides of photosystem II, and nine
      genes encoding polypeptides predicted to comprise the photosystem I light
      harvesting complex. Furthermore, there are five genes encoding early light
      induced proteins and two genes encoding LI818 polypeptides. A candidate for the
      PsbS gene has also been found in the raw genome sequence data (Niyogi, personal
      communication), although no genes encoding homologues of the Sep, or Hli
      polypeptides have been identified. In this manuscript, we identify and classify
      the family of light-harvesting polypeptides encoded on the C. reinhardtii genome.
      This is an important first step in designing specific genetic, biochemical, and
      physiological studies aimed at characterizing the composition, function, and
      regulation of the light-harvesting complexes.

PMID- 14652696
TI  - Resolution of Behcet's disease after HLA-mismatched unrelated cord blood
      transplantation for myelodysplastic syndrome.
AB  - In 1991, a 27-year-old woman who presented with recurrent oral and genital
      ulcers, fever, and erythema nodosum was diagnosed with Behcet's disease (BD). Her
      symptoms were refractory to conventional therapy. In 1999, pancytopenia was
      noticed in this patient for the first time, and in 2000, her white blood cell
      count decreased to 0.94x10(9)/l with 1% myeloblasts and 24% neutrophils. Bone
      marrow examination showed mild hypocellularity with 8% myeloblasts and 6% mature
      neutrophils with dysplastic features. A diagnosis of myelodysplastic syndrome
      (MDS)-refractory anemia with excess blasts was made. Despite marked neutropenia,
      the BD symptoms continued. Since her neutropenia worsened to 0.24x10(9)/l with
      21% neutrophils, the patient underwent cord blood transplantation (CBT) from an
      unrelated donor in July 2001. Myeloid engraftment was documented on day 26. Grade
      I acute graft-versus-host disease occurred, but resolved spontaneously.
      Cyclosporin treatment was reduced gradually and discontinued 6 months after CBT.
      Twenty-three months after CBT, the patient is doing well and has no signs or
      symptoms of BD or MDS. These observations suggest that allogeneic hematopoietic
      stem cell transplantation, which encompasses CBT, may be an effective therapy in
      patients with high-risk aggressive BD.

PMID- 14652698
TI  - Do we need randomised trials to evaluate diagnostic procedures? Against.

PMID- 14652697
TI  - Diagnosis of neuroendocrine tumours by retrospective image fusion: is there a
      benefit?
AB  - This study evaluated the use of image fusion in the preoperative staging of
      neuroendocrine tumors (NET) of the pancreas and the gastrointestinal tract (GIT).
      Thirty-eight patients suffering from a metastasized NET with location of the
      primary in the pancreas ( n=15) or the GIT ( n=23) were examined by somatostatin
      receptor scintigraphy (SRS) and computed tomography (CT). Consecutive image
      registration and fusion were performed using custom-built software integrated in
      AVS/Express (Advanced Visual Systems, Waltham, MA, USA). Registration was
      performed by a voxel-based algorithm based on normalized mutual information.
      Image fusion was feasible in 36/38 patients. A total of 87 foci were assigned to
      anatomical regions (e.g. gut, pancreas, liver, lymph node or others) by two
      independent observers in both SRS and SRS/CT fusion images. The assignments used
      a binary ranking system (1="definite", 0="not definite"). These results were then
      retrospectively compared to the classification of the foci, based on
      postoperative histology or clinical follow-up. Imaging by SRS allowed a definite
      anatomical assignment in 57% (50/87) and 61% (53/87) of all lesions in the case
      of observers A and B, respectively. Image fusion improved the topographic
      assignment to 91% (79/87) and to 93% (81/87). The number classified as "definite"
      by both observers increased from 54% (47/87) to 86% (77/87). The increase in
      definite assignments was highly significant for both observers ( P<0.0001 for
      each). In the case of foci classified as liver metastases, image fusion allowed
      improved assignment to the corresponding liver segment from 45% (18/40) to 98%
      (39/40) and from 58% (23/40) to 100% (40/40) by observers A and B, respectively.
      Furthermore, the improved assignment of foci classified as lesions by image
      fusion was relevant for therapy in 7/36 patients (19%). Therefore, the image
      fusion technique presented herein appears to be a very useful method for clinical
      routine.

PMID- 14652699
TI  - 99mTc-labelled heat-denatured erythrocyte SPET-CT matching to differentiate
      accessory spleen from tumour recurrence.

PMID- 14652700
TI  - Gm and Km immunoglobulin allotypes in Sicily.
AB  - The aim of this study was to evaluate the intra- and inter-population variability
      of the Gm/Km system in the Madonie Mountains, one of the main geographical
      barriers in north-central Sicily. We analysed 392 samples: 145 from Alia, 128
      from Valledolmo, 25 from Cerda and 94 from Palermo. Serum samples were tested for
      G1m (1,2,3,17), G2m (23), G3m (5,6,10,11,13,14,15,16,21,24,28) and Km (1)
      allotypes by the standard agglutination-inhibition method. We found the typical
      genetic patterns of populations in peripheral areas of the Mediterranean basin,
      with a high frequency of haplotypes Gm5*;3;23 and Gm5*;3;. The frequency of
      Gm21,28;1,17;. (about 16%) is rather high compared with other southern areas. Of
      great importance is the presence of the common African haplotype Gm 5*;1,17;.,
      ranging in frequency from 1.56% at Valledolmo to 5.5% at Alia. The presence of
      this haplotype suggests past contacts with peoples from North Africa. The
      introduction of African markers could be due to the Phoenician colonization at
      the end of the 2nd millennium b.c. or to the more recent Arab conquest (8th-9th
      centuries a.d.).

PMID- 14652701
TI  - Imaging of paediatric splenic injury with contrast-enhanced ultrasonography.
AB  - We report two children who sustained traumatic parenchymal splenic injury and
      were monitored with contrast-enhanced ultrasound (CEUS). In both cases,
      unenhanced US failed to diagnose splenic haematoma, but the injury was well
      demonstrated after injection of contrast agent. In one case agreement with CT was
      excellent; in the other, CT was not performed due to the comprehensive
      information provided by CEUS.

PMID- 14652702
TI  - Surgical management of paediatric stroke.
AB  - Childhood cerebrovascular disease is characterised by a wide range of relatively
      rare conditions. The management of a selection of some of the more frequently
      encountered, complex conditions is reviewed. The key to achieving the optimal
      therapeutic strategy for the individual child is multidisciplinary team
      management within a specialist neurovascular team. Access to rehabilitation is
      crucial.

PMID- 14652703
TI  - Increased incidence of CYP2D6 gene duplication in patients with persistent mood
      disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A
      pilot study.
AB  - OBJECTIVE: Recent studies have revealed that genetic polymorphisms of cytochrome
      P(450) 2D6 (CYP2D6) are among the factors that determine the interindividual
      differences in the metabolism and response to antidepressants. We investigated
      the relationship between persistent mood disorders and the duplication of the
      CYP2D6 gene, which encodes an enzyme with increased activity. METHODS: We
      screened the prevalence of the CYP2D6 genotypes in 108 patients with persistent
      mood disorders using long polymerase chain reaction (PCR) and the real-time PCR
      methods. Clinical correlates with the genotypes were also analyzed. RESULTS:
      Among the 108 patients, 81 had failed to respond to antidepressants shown to be
      metabolized by CYP2D6. Of those 81, 8 had a CYP2D6 gene duplication (9.9%, 95%
      confidence interval 3.4-16.4%) which was higher than the 0.8-1.0% incidence
      previously observed in healthy Nordic Caucasians. The worst week scores of the
      Hamilton Depression Rating Scale were higher in the patients with the duplication
      compared with those without the duplication ( P=0.026, student's t-test).
      CONCLUSION: These results suggest that the CYP2D6 gene duplication is a possible
      factor that influences the development of persistence in patients with mood
      disorders probably by ultrarapid drug metabolism.

PMID- 14652704
TI  - Use of psychotropics is high among very old people.

PMID- 14652706
TI  - Retinal slip during active head motion and stimulus motion.
AB  - Gaze control in various conditions is important, since retinal slip deteriorates
      the perception of 3-D shape of visual stimuli. Several studies have shown that
      visual perception of 3-D shape is better for actively moving observers than for
      passive observers watching a moving object. However, it is not clear to what
      extent the improved percept of 3-D shape for active observers has to be
      attributed to corollary discharges to higher visual centers or whether the
      improved percept might be due to improved gaze stabilization during active head
      movements. The aim of this study was to measure binocular eye movements and to
      make a quantitative comparison of retinal slip for subjects instructed to fixate
      a visual stimulus in an active condition (subject makes an active head movement,
      object is stationary) and in a passive condition (the stimulus moves, the subject
      is stationary) for various movement frequencies, viewing distances, and stimulus
      diameters. Retinal slip remains below the "acuity threshold" of about 4 deg/s in
      active conditions, except for the highest frequency tested in this study (1.5 Hz)
      for nearby targets (0.25 cm). Retinal slip exceeds this threshold for most
      passive conditions. These results suggest that the enhanced performance in the
      visual perception of 3-D shape during active head movements can, at least partly,
      be explained by better fixation by actively moving observers.

PMID- 14652705
TI  - On-line compensation for perturbations of a reaching movement is cerebellar
      dependent: support for the task dependency hypothesis.
AB  - Although the cerebellum has been shown to be critical for the acquisition and
      retention of adaptive modifications in certain reflex behaviors, this structure's
      role in the learning of motor skills required to execute complex voluntary goal
      directed movements still is unclear. This study explores this issue by analyzing
      the effects of inactivating the interposed and dentate cerebellar nuclei on the
      adaptation required to compensate for an external elastic load applied during a
      reaching movement. We show that cats with these nuclei inactivated can adapt to
      predictable perturbations of the forelimb during a goal-directed reach by
      including a compensatory component in the motor plan prior to movement
      initiation. In contrast, when comparable compensatory modifications must be
      triggered on-line because the perturbations are applied in randomized trials
      (i.e., unpredictably), such adaptive responses cannot be executed or reacquired
      after the interposed and dentate nuclei are inactivated. These findings provide
      the first demonstration of the condition-dependent nature of the cerebellum's
      contribution to the learning of a specific volitional task.

PMID- 14652708
TI  - Effects of long-term administration of the 5-hydroxytryptamine1B receptor
      antagonist AR-A000002 to guinea pigs.
AB  - RATIONALE: Recently a new 5-hydroxytryptamine1B (5-HT1B)-receptor antagonist, AR
      A000002, was described. It was shown that this compound dose dependently
      increased 5-HT metabolism and release in guinea pig brain following a single
      injection. OBJECTIVES: The present study investigated effects of 3 weeks twice
      daily treatment of guinea pigs with the 5-HT1B-receptor antagonist AR-A000002 on
      the serotonergic neurons and receptor densities. METHODS: Guinea pigs were
      injected subcutaneously with AR-A000002, citalopram or saline twice daily for 3
      weeks. Groups of animals were treated with challenge doses of AR-A000002 or
      saline 24 h after the last chronic treatment (citalopram group 48 h) and
      sacrificed 2 h thereafter. The effect on 5-HT metabolism and 5-HT release was
      assessed. Plasma and brain concentrations of AR-A000002 were analysed. The
      effects on binding of [3H]8-OH-DPAT to 5-HT1A receptors, [3H]GR125743 to 5
      HT(1B/1D) receptors, [3H]ketanserin to 5-HT2A receptors, and [3H]prazosin to
      alpha1-adrenoceptors were determined. RESULTS: Repeated treatment of guinea pigs
      with AR-A000002 did not change the 5-HT(1B/1D), 5-HT1A, 5-HT2A or alpha1
      adrenergic receptor densities. Following repeated treatment of guinea pigs for 3
      weeks with AR-A000002, the 5-HT1B receptors were still receptive to a challenge
      with the same compound. Thus, an increase in the 5-HIAA/5-HT ratio and 5-HT
      release was seen following challenge doses of AR-A000002. No difference in the
      plasma and brain concentrations of AR-A000002 was found between the sub-chronic
      treated AR-A000002 and saline-treated guinea pigs. CONCLUSIONS: It is concluded
      that AR-A000002 is a 5-HT1B receptor antagonist, which enhances persistently the
      serotonergic neurotransmission in guinea pig brain.

PMID- 14652710
TI  - Relationship between ecstasy use and depression: a study controlling for poly
      drug use.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") causes serotonin
      neuron damage in laboratory animals. The serotonin system is known to be
      important in the regulation of mood. Previous research has shown that MDMA users
      score higher on self-report ratings of depression than controls. However, MDMA
      users commonly take other illicit substances and many studies do not fully
      control for poly-drug use. OBJECTIVES: The aim of this study was to examine the
      relationship between MDMA use and affective disturbance, while fully controlling
      for poly-drug use. METHODS: Participants were 30 current MDMA users, 30 poly-drug
      controls who had never used MDMA, 30 drug-naive controls with no history of
      illicit drug use and 20 ex-MDMA users. The current MDMA users and poly-drug
      controls were well matched on all indices of non-MDMA drug use. All participants
      were administered the Beck Depression Inventory (BDI) and the Affective Go/No-go
      task, which has been shown to be sensitive to depression. RESULTS: The current
      and ex-MDMA users scored significantly higher on the BDI than the drug-naive
      controls, but were not significantly different from the poly-drug controls. There
      were no differences between the groups in terms of affective bias scores on the
      Affective Go/No-go task. CONCLUSIONS: Increased scores on self-report depression
      scales in MDMA users are not entirely attributable to MDMA use. MDMA users do not
      show the same attentional bias towards negatively toned material as depressed
      patients.

PMID- 14652711
TI  - Cocaine inhibits cromakalim-activated K+ currents in follicle-enclosed Xenopus
      oocytes.
AB  - The effect of cocaine on K+ currents activated by the KATP channel opener
      cromakalim was investigated in follicular cells of Xenopus oocytes. The results
      indicate that cocaine in the concentration range of 3-500 microM reversibly
      inhibits cromakalim-induced K+ currents. The IC50 value for cocaine was 96
      microM. Inhibition of the cromakalim-activated K+ current by cocaine was
      noncompetitive and voltage independent. Pretreatment with the Ca2+ chelator BAPTA
      did not modify the cocaine-induced inhibition of cromakalim-induced K+ currents,
      suggesting that Ca2+-activated second messenger pathways are not involved in the
      actions of cocaine. Outward K+ currents activated by the application of 8-Br-cAMP
      or forskolin were also inhibited by cocaine. The EC50 and slope values for the
      activation of K+ currents by cromakalim were 184+/-19 microM and 1.14 in the
      absence of cocaine as compared to 191+/-23 microM and 1.03 in the presence of
      cocaine (300 microM). Cocaine also blocked K+ currents mediated through C
      terminally deleted form of Kir6.2 (KirDeltaC26) in the absence of sulfonylurea
      receptor with an IC50 value of 87 microM, suggesting that cocaine interacts
      directly with the channel forming Kir6.2 subunit. Radioligand binding studies
      indicated that cocaine (100 microM) did not affect the binding characteristics of
      the KATP ligand, [3H]glibenclamide. These results demonstrate that cromakalim
      activated K+ currents in follicular cells of Xenopus oocytes are modulated by
      cocaine.

PMID- 14652713
TI  - 32P-postlabeling of DNA adducts arising from complex mixtures: HPLC versus TLC
      separation applied to adducts from petroleum products.
AB  - The carcinogenicity of petroleum products is mainly due to their content of
      polycyclic aromatic compounds (PACs). These compounds may be activated
      metabolically and react with DNA to form DNA adducts, which is a critical event
      in the initiation of cancer. One of the most common techniques for analyzing DNA
      adducts is (32)P-postlabeling. The chromatographic method often used has been
      (32)P-TLC (thin-layer chromatography), but the more recently developed (32)P-HPLC
      (high-performance liquid chromatography) method has shown advantages. The aim of
      this study was to test the hypothesis that the (32)P-HPLC method has a better
      ability of detecting DNA adducts derived from petroleum products than (32)P-TLC.
      It was found that some DNA adducts migrated from the application point in (32)P
      TLC in such a way that it is doubtful if they could be detected and quantified
      properly. It was also found that, when using (32)P-HPLC, it is possible to use
      the same protocol for substances with a wide variety of DNA adduct forming
      potential, whereas (32)P-TLC needs to be optimized regarding time of exposure
      and/or the amount of DNA applied. Further, a pattern of recognition in (32)P-HPLC
      enables a selective assessment of DNA adducts derived from complex mixtures
      whereas (32)P-TLC is very limited when analyzing complex mixtures due to poor
      resolution. With more knowledge about the properties of the most mutagenic DNA
      adducts in HPLC, it could be possible to know also which pattern corresponds to a
      mutagenic or carcinogenic oil. Consequently, (32)P-HPLC is a good alternative
      when assessing the genotoxicity of petroleum products.

PMID- 14652712
TI  - Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid
      treated neuroblastoma cells.
AB  - Okadaic acid (OA) is a tumour promoter that induces apoptosis in several cell
      models. Following previous findings, the objective of this work was to elucidate
      the pathways involved in OA-triggered apoptosis in BE(2)-M17 cells by using a
      combination of pharmacological agents and apoptosis-related assays. OA-induced
      apoptosis involves disruption of F-actin cytoskeleton, activation of caspase-3,
      collapse of mitochondrial membrane potential, DNA fragmentation and decreased
      levels of monomeric Bcl-2 and Bax proteins. All the agents tested were unable to
      obliterate changes in F-actin levels, caspase-3 activation or DNA fragmentation,
      but all of them prevented OA-induced decrease of mitochondrial potential and
      changes in Bax/Bcl-2 levels. Taken together, these results demonstrate that
      collapse of mitochondrial membrane potential is accessory in the execution of
      apoptosis, which is directly dependent on cytoskeletal changes. Mitochondrial
      changes are mediated by complex associations among the Bcl-2 proteins. Cytochrome
      c release from mitochondria is a late event, occurring 24 h after OA exposure.
      Moreover, okadaic acid triggers activation of upstream caspases resembling the
      extrinsic pathway of apoptosis.

PMID- 14652715
TI  - Fixator for the treatment of patellar fractures.

PMID- 14652714
TI  - Identification of aryl-phospho-beta-D-glucosidases in Bacillus subtilis.
AB  - Four aryl-phospho-beta- d-glucosidases were identified in Bacillus subtilis by
      using 4-methylumbelliferyl-phospho-beta- d-glucopyranoside as a substrate. Two of
      these enzymes are the products of the bglA and bglH genes, previously suggested
      to encode aryl-phospho-beta- d-glucosidases, while the other enzymes are encoded
      by the yckE and ydhP genes. Together, these four genes account for >99.9% of the
      glucosidase activity in B. subtilis on aryl-phospho-beta- d-glucosides. yckE was
      expressed at a low and constant level during growth, sporulation, and spore
      germination, and was not induced by aryl-beta- d-glucosides. ydhP was also not
      induced by aryl-beta- d-glucosides. However, while ydhP was expressed at only a
      very low level in exponential-phase cells and germinating spores, this gene was
      expressed at a higher levels upon entry into the stationary phase of growth.
      Strains lacking yckE or ydhP exhibited no defects in growth, sporulation, or
      spore germination or in growth on aryl-beta- d-glucosides. However, a strain
      lacking bglA, bglH and yckE grew poorly if at all on aryl-beta- d-glucosides as
      the sole carbon source.

PMID- 14652716
TI  - Spontaneous outgrowth of EBV-transformed B-cells reflects EBV-specific immunity
      in vivo; a useful tool in the follow-up of EBV-driven immunoproliferative
      disorders in allograft recipients.
AB  - During immunosuppressive medication, Epstein-Barr virus (EBV) infection is
      associated with a risk of developing posttransplant lymphoproliferative disease
      (PTLD). The appropriateness of a spontaneous EBV B-cell transformation (SET)
      assay as a monitor of EBV-specific immunity was evaluated to investigate if it
      safely allows reducing immunosuppressive medication, thereby decreasing the risk
      of developing PTLD. PBMC were isolated longitudinally from 20 pediatric renal
      allograft recipients treated with prednisone and cyclosporine combined with
      either azathioprine or mycophenolate mofetil. Most significantly, EBV-peptide
      specific CD8+ T cells were detectable in the blood of patients with negative SET
      assays, coinciding with significantly lower EBV loads, whereas these cells were
      less frequent in the blood of patients with positive SET assays. Reducing the
      levels of immunosuppression resulted in normalization of the SET assays.
      Therefore, the SET assay is a reflection of the interaction between viral
      replication, transformation of B cells, and EBV-specific immunity in vivo and
      hence a valuable screening test for EBV-driven lymphoproliferative phenomena in
      allograft recipients.

PMID- 14652717
TI  - Recurrence of Budd-Chiari syndrome after liver transplantation in paroxysmal
      nocturnal hemoglobinuria.
AB  - Venous thrombembolism is a major complication of paroxysmal nocturnal
      hemoglobinuria (PNH). Often, veins of atypical localization are afflicted,
      resulting in cerebral, mesenteric, or hepatic venous thrombosis. We present a
      patient who received an orthotopic liver graft for chronic Budd-Chiari syndrome
      in 1988. PNH was the only thrombophilic predisposition identified in this
      patient. After transplantation, he repeatedly suffered from hemorrhage.
      Subsequently, the patient discontinued prophylactic anticoagulation nearly 10
      years after transplantation. Within 6 months Budd-Chiari syndrome recurred, but
      stabilized after anticoagulation therapy with low-molecular-weight heparin was
      reinstituted. The patient is clinically stable 14 years after receiving the liver
      graft. Eleven cases of relapsing Budd-Chiari syndrome have been reported in the
      literature. Of these, four patients suffered from PNH. All patients transplanted
      for PNH-associated Budd-Chiari syndrome in these reports suffered from either
      major bleeding or thrombosis. In conclusion, patients afflicted with PNH appear
      to be at high risk of incurring complications after liver transplantation.

PMID- 14652718
TI  - A comparative evaluation of thermodilution and partial CO2 rebreathing techniques
      for cardiac output assessment in critically ill patients during assisted
      ventilation.
AB  - OBJECTIVE: To evaluate the reliability and clinical value of partial noninvasive
      CO2 (NICO2) rebreathing technique for measuring cardiac output compared with
      standard thermodilution in a group of intensive care nonpostoperative patients.
      DESIGN AND SETTING: Clinical investigation in a university hospital ICU.
      PATIENTS: Twelve mechanically ventilated patients with high (n=6) and low (n=6)
      pulmonary shunt fractions. MEASUREMENTS AND RESULTS: Thirty-six paired
      measurements of cardiac output were carried out with NICO2 and thermodilution in
      patients ventilated in pressure-support mode and sedated with a sufentanil
      continuous infusion to obtain a Ramsay score value of 2. The mean cardiac output
      was: thermodilution 7.27+/-2.42 l/min; NICO2 6.10+/-1.66 l/min; r2 was 0.62 and
      bias -1.2 l/min+/-1.5. Mean values of cardiac output were similar in the low
      shunt group (Qs/Qt < 20), with r2=0.90 and a bias of 0.01 l/min+/-0.4;
      conversely, in the high pulmonary shunt group (Qs/Q > 35%) the mean was 9.32+/
      1.23 l/min with thermodilution and a mean NICO2CO value was 6.97+/-1.53 l/min,
      with r2 of 0.38 and a bias of -2.3 l+/-1.2 min. CONCLUSIONS: The partial CO2
      rebreathing technique is reliable in measuring cardiac output in nonpostoperative
      critically ill patients affected by diseases causing low levels of pulmonary
      shunt, but underestimates it in patients with shunt higher than 35%.

PMID- 14652719
TI  - Protein expression changes in a cell system of beta-cell maturation reflect an
      acquired sensitivity to IL-1beta.
AB  - AIM/HYPOTHESIS: Type 1 diabetes mellitus (T1DM) is caused by specific destruction
      of the pancreatic beta cells in the islets of Langerhans. Increased sensitivity
      to cytokines, in particular to interleukin-1beta (IL-1beta) seems to be an
      acquired trait during beta-cell maturation. In response to cytokines both
      protective and deleterious mechanisms are induced in beta cells, and when the
      deleterious prevail, T1DM develops. The aims of this study were to identify
      perturbation in protein patterns (PiPP) associated with beta-cell maturation, and
      compare these changes to previous analyses of IL-1beta exposed rat islets. For
      this purpose, proteome analyses were carried out using a cell-line, which matures
      from a glucagon-producing pre-beta-cell phenotype (NHI-glu) to an insulin
      producing beta-cell phenotype (NHI-ins). We have previously shown that this
      maturation is accompanied by acquired sensitivity to the toxic effects of IL
      1beta. METHODS: 2D-gel electrophoresis was used to separate the proteins and
      MALDI-MS and database searches were performed to identify the proteins. RESULTS:
      During beta-cell maturation 135 protein spots out of 2239 detectable changed
      expression levels. Of these, 74 were down-regulated, 44 up-regulated, 16 were
      suppressed and 1 was expressed de novo. Using MALDI-MS, positive identification
      was obtained for 93 out of the 135 protein-spots revealing 97 different proteins.
      Of these, 22 proteins were in common with changes identified in previous proteome
      analysis of perturbation in protein pattern in IL-1beta exposed rat islets.
      Several of the proteins were present in more than one spot suggesting post
      translational modification. CONCLUSION/INTERPRETATION: Several proteins and
      protein modifications were identified that could be critically involved in beta
      cell maturation, insulin-gene expression and the acquired IL-1beta sensitivity.

PMID- 14652720
TI  - 11beta-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes.
AB  - Obesity and Type 2 diabetes mellitus are associated with abnormal regulation of
      glucocorticoid metabolism that are highlighted by clinical similarities between
      the sequelae of insulin resistance and Cushing's syndrome, as well as
      glucocorticoids' functional antagonism to insulin. 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) activates functionally inert glucocorticoid
      precursors (cortisone) to active glucocorticoids (cortisol) within insulin target
      tissues, such as adipose tissue, thereby regulating local glucocorticoid action.
      Recent data, mainly from rodents, provide considerable evidence for a causal role
      of 11beta-HSD1 for the development of visceral obesity and Type 2 diabetes though
      data in humans are not unequivocal. This review summarizes current evidence on a
      possible role of 11beta-HSD1 for development of the metabolic syndrome, raising
      the possibility of novel therapeutic options for the treatment of Type 2 diabetes
      by inhibition or down-regulation of 11beta-HSD1 activity.

PMID- 14652722
TI  - [Mass casualties after an explosion].
AB  - Because of the intifada, the Israeli-Palestinian conflict has become
      characterized by violence against civilians on both sides. Since the early 1990s,
      this conflict has seen directed operations performed by suicide attackers, whose
      goal is to kill civilians who are not direct participants in the confrontation.
      For urban and local hospitals this means that they must always be aware of being
      confronted with limited multiple-casualty incidents. This has required a
      restructuring of emergency plans at the scene and in the hospital. At the scene
      the incident is classified according to the number and degree of injury of the
      victims. The accumulation of such incidents made it necessary in Israel to change
      views of the system of triage, which has essential differences from the central
      European system. Apart from changing preclinical and clinical management
      algorithms, the surgeons specialized in casualties must be prepared for a new
      quality of injuries. Barotrauma of the lung and multiple, seemingly superficial
      injuries often only emerge later as life-threatening and lead to the paralysis of
      intensive care and surgical capacity.

PMID- 14652723
TI  - [Manipulation of the step borer as cause of too shallow boring depth in the
      femoral neck with the gamma nail system].
AB  - The gamma nail step drill has been sold over 500,000 times worldwide. Depending
      on the construction used and the way it is handled, it can lead to a drill depth
      in the femoral head that is too shallow if the anatomic dimension of the femoral
      neck is rather long. Whenever the relationship between rotational speed and drive
      force is unfavorable, as it is by hand reaming, the triple-bladed drill only
      produces a triangular hole in the lateral cortical bone. Subsequently, it draws
      itself through this hole like a screw, without forming the hole into a complete
      circle. The drill shaft expands conically along its length preventing it from
      passing through the hole in the cortical bone at a depth of 90 mm. Until now,
      this phenomenon has been traced back to blunt drills or perhaps curved guide
      wires. Since the lag screws that have been used could not be screwed into
      undrilled cancellus bone, screws have sometimes been implanted at a sub-optimal
      length. The problem was noticed, however, and documented in experiments, and
      potential solutions were proposed.

PMID- 14652721
TI  - Short-term postural reflexes in diabetic patients with autonomic dysfunction.
AB  - AIMS/HYPOTHESIS: Assessment of autonomic dysfunction provides prognostic data in
      diabetic patients. Clinical tests are limited to heart rate variability and blood
      pressure measurements. We investigated whether a detailed analysis of postural
      reflexes of patients during short-term head-up tilting and standing erect (both
      for 3 min) would provide useful clinical data. METHODS: We studied 14 control
      subjects and 56 patients with Type 2 diabetes, stratified into four matched
      groups: uncomplicated, micro-albuminuria, macro-albuminuria and autonomic
      neuropathy, who were tilted 55 degrees three times and were standing erect. Non
      invasive finger plethysmography blood pressure measurements, using the Portapres,
      and impedance cardiac output measurements, using the RheoCardioMonitor, were
      continuously recorded throughout the study. Wavelets of the response to tilting
      and standing were drawn. The wavelets for the three tilts were combined to
      improve definition. The degree of autonomic dysfunction was quantified by
      calculating the baroreflex sensitivity index from the heart-rate and blood
      pressure variability data. RESULTS: Baroreflex sensitivity data confirmed that
      autonomic dysfunction increased as diabetic complications worsened (p<0.001).
      Both standing and tilting resulted in an initial decrease in blood pressure
      followed by recovery, an increase in heart rate which was more pronounced with
      standing and a decrease in stroke volume. Characteristic and incremental changes
      in these responses were noted as the complications of diabetes worsened
      (p<0.001). These were a greater decrease in blood pressure with loss of the
      recovery phase, a reduced heart-rate response and paradoxically an increase in
      stroke volume. CONCLUSION/INTERPRETATION: Non-invasive blood-pressure and stroke
      volume measurements recorded during short-term tilting and standing promises to
      be useful in assessing diabetic autonomic dysfunction.

PMID- 14652724
TI  - [Secondary decompression trepanation in progressive post-traumatic brain edema
      after primary decompressive craniotomy].
AB  - Besides evacuation of epidural or subdural hematoma, early decompressive
      craniectomy with duraplasty has to be performed in the neurotraumatological care
      of patients with moderate [Glasgow Coma Scale (GCS) score 9-12 points] or severe
      traumatic brain injury (TBI; GCS score </=8 points) and threatening herniation.
      The efficacy of secondary decompressive craniectomy and duraplasty after primary
      trepanation is under debate due to missing evidence of improved outcome. The
      objectives of this study were to register the incidence of increasing brain edema
      after isolated TBI and primary craniectomy, to identify possible decision
      criteria for secondary decompressive trepanation, and to evaluate the
      neurological performance 6 months after discharge with the Glasgow Outcome Score
      (GOS). Of 131 patients who suffered from isolated TBI and had to be primarily
      operated between January 1997 and December 2001, 58 (male:female = 48:10; median
      age of 50.9 years) were included in this analysis. In 11 patients (male:female =
      9:2; median age of 40.0 years) a secondary unilateral extensive or contralateral
      decompressive craniectomy had to be performed in the clinical course. Four of the
      11 patients (36.4%) did not survive TBI; they died at a median of 1 day after
      revision or 6 days after TBI, respectively. In the group of secondary
      decompressive craniectomy we recorded admission (80.0 min after TBI) 35 min later
      ( p=0.009) than in the group of primary trepanation. Prehospital otorrhagia was
      observed more frequently ( p=0.036). In univariate analysis, arterial hypotension
      ( p=0.018) and otorrhagia at admission ( p=0.035), intracranial pressure (ICP)
      immediately after primary operation ( p=0.024), and decrease of maximal
      postoperative cerebral perfusion pressure (CPP; p=0.031) below the median cutoff
      value of 70 mmHg correlated with the event of secondary decompression
      craniectomy. Multivariate analysis identified decreased maximal CPP after primary
      trepanation as the only independent prognostic parameter (score 10.496; df=1;
      p=0.043) for the necessity of secondary trepanation and unfavorable GOS 6 months
      after discharge. In patients with isolated moderate or severe TBI, prehospital
      arterial hypotension as well as otorrhagia negatively influenced the mortality
      and morbidity. Therefore, early adjustment of arterial hypotension and the rapid
      transport into a neurotraumatological center are to be required for prehospital
      management of TBI patients. The decrease of maximal CPP below 70 mmHg despite
      administration of catecholamines representing the only independent prognostic
      parameter during monitoring in the intensive care unit seems to indicate the
      necessity of an operative revision as well as an unfavorable GOS 6 months after
      discharge.

PMID- 14652726
TI  - [The "Shoulder, Arms and Hand Disability Questionnaire" as a scale for
      identification of the diagnosis-specific activity profile].
AB  - Functional disabilities of the upper extremities have a considerable social and
      economic impact so that interest was aroused in developing a valid and reliable
      instrument suitable for international use. The Disabilities of the Arm, Shoulder,
      and Hand questionnaire is a self-report measure recording functional limitations
      in the upper extremity. A German version is now available in German-speaking
      countries. Previous studies have been concerned with the evaluation of DASH
      scores. Based on the data of four diagnostic groups, this study explores DASH's
      ability to identify diagnosis-specific limitations at the item level. The data
      were pooled and examined with regard to significant differences within the
      groups. Diagnosis-specific limitations could be identified within all groups,
      indicating that DASH is capable of expressing diagnostic entities as well as
      summed scores. Consideration of the individual profiles opens the possibility of
      using DASH as a prognostic tool to anticipate functional problems arising during
      rehabilitation following surgical interventions.

PMID- 14652725
TI  - [Reconstruction of big rotator cuff ruptures. A new technique of tendon
      refixation with the corkscrew suture anchor system].
AB  - Tendon retraction and fatty degeneration is a major problem in repair of massive
      rotator cuff tears. Especially in the transosseous refixation technique, a
      tension-free refixation cannot be obtained in all cases. The purpose of this
      prospective study was to evaluate the postoperative results using a new tension
      free reinsertion technique with a Corkscrew suture anchor system. Thirty patients
      (25 males, 5 females) with complete one and two tendon tears underwent open
      rotator cuff repair (rupture of one tendon: n=14, 47%). The torn tendons were
      mobilized and reinserted medially to reduce tension. Medialization was achieved
      by inserting tendon near the osteochondral border in a bony trough. The number of
      implanted suture anchors ranged from 2 to 6 (mean: 3.56). The mean age was 56
      years (39-68 years) with a follow-up of 24 months (17-33 months). In one patient
      physical and sonographic examination showed a complete and in two patients a
      partial rerupture. A temporarily frozen shoulder occurred in two cases. No
      infection or rejection response was seen. In no case was revision surgery
      necessary. No displacement or loosening of the Corkscrew anchors was noticed. The
      constant score improved from 45 points preoperatively to 85 points at the time of
      follow-up (mean). The Corkscrew suture anchor system in combination with the new
      suture technique offers the possibility of a stable reinsertion even in reduced
      calcified bone structure. This facilitates good conditions for stable
      fibroblastic healing. Our midterm results show good osseous union combined with a
      low rerupture rate.

PMID- 14652727
TI  - [Para-articular, periprosthetic fracture in a case with total knee endoprosthesis
      using the Ilizarov hybrid fixator].
AB  - Periprothetic fractures near the knee joint must always be regarded as very
      severe fractures. Early mobilisation and low stress during surgery are the
      essential points in deciding which method of surgery to use. The Ilizarov frame
      can be very successful in individual cases. A hybrid frame can reduce the time of
      surgery substantially. This method is presented in two case reports.

PMID- 14652728
TI  - [Extravertebral cement drainage with occlusion of the extradural venous plexus
      into the vena cava after vertebrobplasty. Case report and review of the
      literature].
AB  - This paper presents the case report of an 88 year old female who came to hospital
      suffering from a severe lower back pain. Ten days before, she had undergone a
      vertebroplasty with injection of cement into lumbar vertebra 3 because of an
      osteoporotic fracture. This treatment did not result in a reduction of the lower
      back pain, which was the main reason for the procedure. However, the patient
      claimed to have increasing pain radiating to her left leg. Furthermore, she
      suffered from numbness of her left leg. Clinical examination showed a lack of
      power in this leg according to hip flexion with a degree of 3/5. X-ray
      examinations showed paravertebral cement particles and led to the suspicion that
      the paravertebral cement had caused nerve root compression. MRI and CT
      myelography showed that the cement had drained into the intraspinal, extradural
      venous plexus (Batson's plexus). The plexus was filled out with cement between L2
      and L5 on both sides. There was nearly no cement in the fractured vertebra L3,
      but cement had also run onto the paravertebral veins up to the vena cava, which
      was also involved. The cemented veins had led to a stenosis of the neuroforamina
      L2 and L3 on the left side. The result was compression of left L3 nerve root.
      After consulting with our vascular surgeons, we decided on a non-operative
      treatment. We prescribed a lumbar brace as external stabilisation and as an
      antithrombotic treatment we gave the patient weight adapted low molecular weight
      heparin.

PMID- 14652729
TI  - [Foot injury as a rare cause of scendosporiosis with fetal outcome].
AB  - After an attempted suicide with a fall from a height of 5 m, a 33 year old male
      suffered a subarachnoidal haemorrhage, an instable fracture of the second lumbar
      vertebra as well as a soft-tissue decollement in the vicinity of the right heel.
      Despite surgical management, the comatose patient showed slow wound-healing of
      the heel, making revision-surgery necessary 10 days after the first treatment.
      Fungi were histologically recognised, and subsequent culturing identified
      Scedosporium apiospermum. Systemic antimycotic therapy with itraconazol (800
      mg/d) was immediately initiated. Despite this, S. apiospermum was repeatedly
      found in wound swabs over the following 2 weeks. After 4 weeks, a
      radiographically verified osteomyelitis of the calcaneus was diagnosed and local
      debridement was once again performed. After 5 days, an MRI of the cranium
      suggested an abscess in the posterior horn of the left lateral ventricle.
      Itraconazol was altered to voriconazol (4 mg/kg body weight). Neurosurgical
      opening of the abscess and subsequent culturing once again showed S. apiospermum.
      CT-scans performed over the following period showed an increase in lesions in the
      brain suggestive for numerous abscesses. At 78 days after the initial trauma, the
      still comatose patient died due to a massive cerebral haemorrhage.
      Microbiological assessment of the soil at the site of injury revealed S.
      apiospermum.

PMID- 14652730
TI  - [Thoughts on the economic aspects of management of severely injured patients with
      reference to "diagnostic related groups" (DRG). An initiative of the Specialized
      Committee of the German Health Care System].

PMID- 14652731
TI  - [A new irrigation-suction boring system facilities low-pressure intramedullary
      boring of isolated swine femurs].
AB  - AIM: Intramedullary nailing is the treatment of choice for the stabilization of
      fractures of long tubular bones. An important disadvantage of this method is the
      increase in intramedullary pressure and the resulting release of fat into the
      venous blood system during reaming of the medullary canal. We have developed a
      new type of rinsing-suction-reamer (SSB) in order to minimize these
      disadvantages. Trials were initiated to investigate whether it is possible to
      ream the medullary canal with the SSB without pressure increase in comparison
      with the standard AO-reamer (AOB). METHODS: Reamed intramedullary nailing was
      performed in 20 isolated pig femora. The intramedullary pressure was recorded
      continuously. RESULTS: While stepwise reaming was performed, the pressure only
      rose above the physiological level in AOB. During insertion of the guide wire and
      the nail, comparable values were measured for AOB and SSB. CONCLUSION: Our
      experiments show that reaming of the medullary canal is possible without a
      pressure increase using the SSB in comparison with AOB.

PMID- 14652732
TI  - Salivary thromboplastic activity in diabetics and healthy controls.
AB  - Coagulative function of saliva derives from the thromboplastin found in saliva.
      It may establish hemostasis in the mouth. Salivary disfunction and changes in
      salivary composition and are frequent complications of diabetes. This study
      investigated the influence of some local etiologic and systemic factors on
      salivary thromboplastic activity (STA) in diabetics. In this study, cytological
      smears and biochemical tests were used. STA was measured by Quick's one stage
      method, serum glucose by the glucose oxidase method, and salivary protein by the
      method of Lowry. STA was almost the same in the diabetic and control groups. The
      only statistically significant difference within the diabetic group was found to
      be due to antibiotic usage. STA, i.e. clotting time, was 30% longer (114 s) (
      p<0.05) and salivary protein (4.07 mg ml(-1)) ( p<0.1) was lower in diabetics not
      taking antibiotics than in those taking them. No such differences were observed
      in the healthy controls. Significant linear correlations ( p<0.05) with respect
      to STA were with salivary protein in the control group (r=0.61) and in the
      diabetic group (r=0.51) and with antibiotic usage (r=0.29), with leukocyte cell
      count (r=0.27) in the diabetic group. It can be concluded that salivary cells,
      proteins and antibiotic usage are important for STA.

PMID- 14652733
TI  - Subjective image quality of digital panoramic radiographs displayed on monitor
      and printed on various hardcopy media.
AB  - The subjective image quality of panoramic radiographs shown on a diagnostic
      computer monitor were compared with professional direct thermal prints and with
      common inkjet prints on different paper qualities. Indirect digital panoramic
      radiographs were obtained from 15 patients. The images were printed with a direct
      thermal printer in their original format. Afterwards, these were loaded in an
      imaging software programme (Microsoft Photo Editor) and assessed both on computer
      monitor and inkjet prints on transparency, glossy, satin and regular paper. Five
      observers assessed subjective image quality for different regions and anatomical
      landmarks on a 5-point rating scale. Data were statistically analysed and inter-
      and intra-observer performances were calculated. Best image quality was obtained
      with direct thermal prints, followed in descending order by panoramic images
      viewed on the monitor, inkjet prints on transparencies, glossy paper, satin paper
      and finally regular paper. The differences were significant except for monitor
      images versus direct thermal prints, inkjet-transparencies and inkjet-glossy
      images and inkjet-satin versus inkjet-glossy images. The subjective image quality
      of indirect digital panoramic images is different for images shown on the
      computer monitor and for printed images depending on both the printer and paper
      type used.

PMID- 14652734
TI  - Gene expression profiling of mouse Sertoli cell lines.
AB  - The proliferation and differentiation of Sertoli cells is regulated by follicle
      stimulating hormone (FSH). The molecular events following FSH stimulation are
      only partially known. To investigate FSH action in Sertoli cells, we established
      two novel FSH-responsive mouse Sertoli-cell-derived lines expressing human wild
      type (WT) FSH receptor (FSHR) or overexpressing mutated (Asp567Gly)
      constitutively active FSHR (MUT). Gene expression profiling with commercially
      available cDNA arrays, including 588 mouse genes, revealed 146 genes expressed in
      both cell lines. Compared with the expression pattern of WT cells, 20 genes were
      identified as being either up- or down-regulated (>two-fold) in the MUT cells. We
      observed a strong differential expression of factors involved in cellular
      proliferation, e.g. cyclin D2 (repressed to nearly undetectable levels),
      proliferating cell nuclear antigen (2.5-fold repression) and Eps-8 (six-fold
      repression), and in genes involved in cellular differentiation, e.g. cytokeratin
      18 (13-fold induction). The cDNA array results for six representative genes were
      confirmed by Northern blotting, which also included the parental SK-11 cell line
      devoid of FSHR expression. We found no further acute FSH- or forskolin-induced
      change in expression levels after 3-h stimulations, suggesting that the observed
      differences between the two cell lines is a consequence of mild, chronically
      increased, cAMP production in MUT cells. These results provide a platform for the
      further investigation of selected candidate genes in primary cultures and/or in
      vivo.

PMID- 14652735
TI  - Genes expressed in zoospores of Phytophthora nicotianae.
AB  - The genus Phytophthora includes many highly destructive plant pathogens. In many
      Phytophthora species, pathogen dispersal and initiation of plant infection are
      achieved by motile, biflagellate zoospores that are chemotactically attracted to
      suitable infection sites. In order to study gene expression in zoospores, we have
      constructed a cDNA library using mRNA from zoospores of Phytophthora nicotianae.
      The library was arrayed and screened using probes derived from mycelium or
      zoospore mRNA. More than 400 clones representing genes preferentially expressed
      in zoospores were identified and sequenced from the 5' end of the insert. The
      expressed sequence tags (ESTs) generated were found to represent 240 genes. The
      ESTs were compared to sequences in GenBank and in the Phytophthora Genome
      Consortium database, and classified according to putative function based on
      homology to known proteins. To further characterize the identified genes, a
      colony array was created on replicate nylon filters and screened with probes
      derived from four Phytophthora developmental stages including zoospores,
      germinating cysts, vegetative mycelium and sporulating hyphae, and from
      inoculated and uninoculated tobacco seedlings. Data from sequence analysis and
      colony array screening were compiled into a local database, and searched to
      identify genes that are preferentially expressed in zoospores for future
      functional analysis.

PMID- 14652736
TI  - LexA-binding sequences in Gram-positive and cyanobacteria are closely related.
AB  - The lexA gene of the cyanobacterium Anabaena sp. strain PCC7120 has been cloned
      by PCR amplification with primers designed after TBLASTN analysis of its genome
      sequence using the Escherichia coli LexA sequence as a probe. After over
      expression in E. coli and subsequent purification, footprinting experiments
      demonstrated that the Anabaena LexA protein binds to the sequence
      TAGTACTAATGTTCTA, which is found upstream of its own coding gene. Directed
      mutagenesis and sequence comparison of promoters of other Anabaena genes, as well
      as those of several cyanobacteria, allowed us to define the motif RGTACNNNDGTWCB
      as the LexA box in this bacterial phylum. Substitution of a single nucleotide in
      this motif present in the Anabena lexA promoter is sufficient to enable it to
      bind the Bacillus subtilis LexA protein. These data indicate that Cyanobacteria
      and Gram-positive bacteria are phylogenetically closely related.

PMID- 14652737
TI  - Fission yeast Cdc37 is required for multiple cell cycle functions.
AB  - The identification of a Schizosaccharomyces pombe homologue of the cdc37 gene is
      described. The gene product is most similar to the budding yeast homologue, but
      shows similarity to metazoan Cdc37 proteins, with a region of high similarity at
      the extreme N-terminus. Gene transplacement experiments in diploid cells followed
      by tetrad dissection show that the gene is essential. Depletion of the gene
      product after switching off expression of cdc37 from the regulatable nmt81
      promoter results in cessation of growth and division. The cells arrest
      heterogeneously, with a significant proportion showing mitotic defects;
      paradoxically, a proportion of the cells show a short-cell phenotype consistent
      with an advanced cell cycle.

PMID- 14652738
TI  - Retrotransposon-based molecular markers for linkage and genetic diversity
      analysis in wheat.
AB  - Retrotransposon-based molecular markers have been developed to study bread wheat
      ( Triticum aestivum) and its wild relatives. SSAP (Sequence-Specific
      Amplification Polymorphism) markers based on the BARE-1/ Wis-2-1A
      retrotransposons were assigned to T. aestivum chromosomes by scoring nullisomic
      tetrasomic chromosome substitution lines. The markers are distributed among all
      wheat chromosomes, with the lowest proportion being assigned the D wheat genome.
      SSAP markers for BARE-1/ Wis-2-1A and three other wheat retrotransposons, Thv19,
      Tagermina and Tar1, are broadly distributed on a wheat linkage map. Polymorphism
      levels associated with these four retrotransposons vary, with BARE-1/ Wis-2-1A
      and Thv19 both showing approximately 13% of bands polymorphic in a mapping
      population, Tagermina showing approximately 17% SSAP band polymorphism and Tar1
      roughly 18%. This suggests that Tagermina and Tar1 have been more
      transpositionally active in the recent evolutionary past, and are potentially the
      more useful source of molecular markers in wheat. Lastly, BARE-1 / Wis-2-1A
      markers have also been used to characterise the genetic diversity among a set of
      35 diploid and tetraploid wheat species including 26 Aegilops and 9 Triticum
      accessions. The SSAP-based diversity tree for Aegilops species agrees well with
      current classifications, though the Triticum tree shows several significant
      differences, which may be associated with polyploidy in this genus.

PMID- 14652739
TI  - Template jumping by a LINE reverse transcriptase has created a SINE-like 5S rRNA
      retropseudogene in Dictyostelium.
AB  - Short interspersed nuclear elements (SINEs) are non-autonomous retroelements that
      mimic the 3' ends of so-called long interspersed nuclear elements (LINEs) to
      ensure their propagation by proteins encoded by autonomous LINEs. The
      Dictyostelium discoideum genome contains a family of LINE-like retrotransposons
      that specifically target tRNA genes for integration (TRE elements). We describe
      here a retrotransposed ribosomal 5S RNA pseudogene in the D. discoideum genome
      that contains at its 3' end an 8-bp sequence derived from the 3' end of a TRE and
      a polyadenine tail. The r5S "retropseudogene" is flanked by target-site
      duplications that are characteristic for TREs, and is inserted upstream of a tRNA
      gene, just like a typical TRE. The D. discoideum r5S retropseudogene has
      structural features of a SINE, but has not been amplified, probably due to the 5'
      truncation that occurred upon its initial retrotransposition. The discovery of
      this D. discoideum r5S retropseudogene reveals that SINEs can be created de novo
      during reverse transcription of LINE transcripts, if the LINE-encoded reverse
      transcriptase dissociates from the LINE RNA and jumps to other cellular RNAs
      particularly genes transcribed by RNA polymerase III-to create continuous mixed
      cDNAs.

PMID- 14652740
TI  - The comparative metabolism of triclabendazole sulphoxide by triclabendazole
      susceptible and triclabendazole-resistant Fasciola hepatica.
AB  - Benzimidazole anthelmintics are widely used against nematode, cestode and
      trematode parasites. The drugs undergo several enzyme-mediated reactions within
      the host animal that produce a number of metabolites. Although it has been shown
      that certain helminths, including Fasciola hepatica, can metabolise albendazole,
      nothing is known regarding the ability of the liver fluke to metabolise
      triclabendazole, which is the major flukicidal compound currently on the market.
      In the current study, adult triclabendazole-susceptible flukes were treated with
      triclabendazole sulphoxide in vitro, and the metabolism of the drug was monitored
      by high performance liquid chromatography. The data show that F. hepatica can
      metabolise triclabendazole sulphoxide into its relatively inert sulphone
      metabolite. Parallel experiments using triclabendazole-resistant flukes showed
      that the conversion of triclabendazole sulphoxide to triclabendazole sulphone was
      on average 20.29% greater in the resistant flukes compared with the susceptible
      flukes. The results are discussed with regard to the mechanism of triclabendazole
      resistance in F. hepatica.

PMID- 14652741
TI  - Efficacy of an experimental fasciolicide against immature and mature Fasciola
      hepatica in artificially infected calves.
AB  - The efficacy of 5-chloro-2-methylthio-6-(1-naphthyloxy)- 1H-benzimidazole, called
      "alpha", was tested against Fasciola hepatica. Fluke-free calves ( n=32) were
      divided into 8 groups and infected with 150 metacercariae per animal. All animals
      subsequently received a second infection with another 150 metacercariae, given at
      different time intervals aimed to produce flukes of differing ages within the
      experimental animals. When the flukes reached the required age in the animals,
      four groups were treated with a single oral dose of 12 mg/kg of compound alpha
      and the remaining ones served as non-treated controls. Two weeks after treatment
      the animals of all groups were sacrificed and the livers were removed to
      determine the numbers of parasites present in the treated and untreated controls.
      In the treated groups the fluke reduction for the 3 day/2 week group was 100%,
      for the 3 week/4 week group it was 96.4%, for the 6 week/8 week group it was
      99.2% and for the 10 week/12 week group it was 100%.

PMID- 14652742
TI  - A cysteine protease from Taenia solium metacestodes induce apoptosis in human
      CD4+ T-cells.
AB  - Here we investigated whether the depletion of CD4+ lymphocytes, observed in
      mononuclear cells incubated with Taenia solium metacestode E/S products or with
      living cysts was due to apoptosis. Using the deoxynucleotidyl transferase
      mediated dUTP nick-end labelling (TUNEL), electron microscopy and DNA gel
      electrophoresis, we found signs of apoptosis in these cells. Results showed that
      cysteine protease activity was responsible for this effect, since E-64 prevented
      cell death in all cases. Electron microscopy studies showed that lymphocytes
      exhibited features of apoptosis such as cellular membrane integrity, strangling
      and fragmentation of nuclei, chromatin condensation, apoptotic bodies and loss of
      microvilli. In contrast, lymphocytes co-cultured with living metacestodes plus E
      64 exhibited integrity of their structures. DNA fragmentation was detected by
      TUNEL assays and DNA gel electrophoresis. The results suggested that cell death
      induced by the cysteine protease from the T. solium metacestode may be involved
      in down-regulation of cell-mediated responses in infected hosts.

PMID- 14652743
TI  - 4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II
      inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia
      malayi.
AB  - A compound of the coumarin class, 4-methyl-7-(tetradecanoyl)-2H-1-benzopyran-2
      one, was evaluated for antifilarial activity against the human filarial parasite,
      Brugia malayi (sub-periodic strain) in Mastomys coucha. The test compound brought
      about a 24.4% reduction in circulating microfilaremia on day 8 after initiation
      of treatment when administered by the peritoneal route at a dose of 50 mg/kg for
      5 consecutive days. The compound also caused a 62.0% mortality in adult
      parasites. Apart from killing adult filariids, it also brought about
      sterilization of 81.8% of the surviving female B. malayi. An oral dose of 200
      mg/kg for 5 consecutive days was less effective (35.5% adulticidal efficacy and
      65.8% sterilization). In vitro, the compound killed adult B. malayi at 100 microM
      concentration and inhibited DNA topoisomerase II activity in the filarial
      parasite. Studies are in progress using the compound in combination with standard
      antifilarials as well as other active agents.

PMID- 14652744
TI  - Vertical transmission of Toxocara cati Schrank 1788 (Anisakidae) in the cat.
AB  - In eight cats and their offspring the mode of transmission of Toxocara cati
      following natural and experimental infection was investigated in three
      experiments. In experiments 1 and 2 the kittens of four cats with a chronic
      natural infection and of four cats with an acute experimental infection,
      respectively, were examined. In experiment 3 two queens of experiment 2 were
      mated again to examine whether in the adult cat "dormant" larvae exist in the
      tissue, that can be reactivated during pregnancy or lactation to infect the
      offspring. Additionally, the muscle tissue and organs of two adult cats, one with
      chronic one with acute infection, were examined for hypobiotic larvae. Pre-natal
      infections with T. cati did not occur in experiments 1 or 2. In none of the
      kittens that were examined directly after birth were larvae found. In the
      offspring of experiment 1 one single larva of T. cati was found 28 days post
      partum. Whereas in the kittens of experiment 2 up to 333 larvae were found in one
      animal. Lactogenic transmission of larvae occurs after acute infection of the
      queen during late pregnancy but not during chronic natural infection. There is no
      evidence for the existence of arrested somatic larvae in the adult cat as an
      important host-finding strategy in the life cycle of T. cati. Following milk
      borne infections, the majority of larvae seem to undergo direct development in
      the intestine without tracheal migration. Only a small number of larvae was found
      in other organs.

PMID- 14652745
TI  - Trypanosoma avium: experimental transmission from black flies to canaries.
AB  - Trypanosomes identified as Trypanosoma avium were found in the ornithophilic
      black flies ( Eusimulium latipes) attacking buzzard nestlings ( Buteo buteo).
      Parasites formed plugs and rosettes in the hindgut of the vector and were
      attached on the cuticular lining of the black fly anterior intestine (ileum) by
      hemidesmosome-like plaques. Hindgut stages from infected black flies were
      experimentally transmitted into canaries ( Serinus canaria) by ingestion of
      vectors and by contamination of host conjunctiva. This is the first clear
      evidence of such transmission in avian trypanosomes. Parasites survived in
      peripheral blood of birds at the least 10 months. In contrast to the direct
      inoculation of insect stages, parasites from culture failed to produce infection
      in experimental birds; this has consequences for laboratory studies of host
      susceptibility and transmission.

PMID- 14652746
TI  - Transmission dynamics of a trematode parasite: exposure, acquired resistance and
      parasite aggregation.
AB  - This paper examines the relative importance of exposure and susceptibility to the
      infection of rainbow trout ( Oncorhynchus mykiss) with the trematode parasite
      Diplostomum spathaceum under natural conditions. A total of 93 individually
      marked, similarly aged fish were introduced into three cages at regular time
      intervals and the intensity of infection in individuals recorded by counting
      parasites in live fish using ophthalmic techniques. Fish introduced into the
      cages became infected faster than fish that were already in the cages, indicating
      that fish developed resistance to infection after repeated exposure. Fish kept in
      the cages experienced similar levels of exposure and the distribution of
      parasites between these fish was not significantly different from a random
      distribution. In contrast, parasites from 16 Finnish wild roach populations were
      highly aggregated. The differences between the caged fish and the wild fish
      indicate that the aggregated distribution in wild fish might be determined by
      variations in exposure rather than variations in susceptibility between fish.
      This is one of the few studies to demonstrate the development of resistance in
      fish against the parasite under natural conditions, and to attempt to separate
      exposure and susceptibility as causative agents of parasite aggregation.

PMID- 14652747
TI  - Simultaneous detection and differentiation of Theileria and Babesia parasites
      infecting small ruminants by reverse line blotting.
AB  - Characteristic sequence signatures were identified within the hypervariable
      region 4 (V4 region) of the small ribosomal RNA gene of ovine/caprine piroplasm
      species including Theileria lestoquardi, T. ovis, T. separata, Babesia ovis, B.
      motasi, B. crassa [comprising strains B. crassa (Iran) and B. crassa (Turkey)]
      and several novel species: Theileria sp. 1 (China), Theileria sp. 2 (China) and
      Babesia sp. (China), [comprising strain Babesia sp. (Lintan), and Babesia sp.
      (Ningxian)] as defined previously. Based on the ascertained gene variations a
      reverse line blotting (RLB) assay was developed enabling direct, concurrent,
      highly specific and sensitive identification of virtually all presently known
      ovine/caprine piroplasm species. All probes bound to their respective target
      sequence only, therefore, no cross-reaction was observed resulting in clear
      recognition of either individual strains, species or groups. No signal was
      observed when ovine and caprine genomic DNA was used as the control,
      demonstrating that the signals are due to the presence of parasite DNA in
      investigated samples. Furthermore, the sensitivity of RLB could be considerably
      enhanced to detect a parasitemia level of at least 10(-12)% by reamplification of
      PCR products (nested PCR) thereby substantially increasing the possibility of
      identifying carrier animals.

PMID- 14652748
TI  - Recommended clinical evaluation of infants with an apparent life-threatening
      event. Consensus document of the European Society for the Study and Prevention of
      Infant Death, 2003.
AB  - Infants with an apparent life-threatening event (ALTE) should not be treated nor
      monitored without a detailed medical evaluation, as different medical causes may
      be responsible for the initial clinical presentation. Standard and specific
      evaluation procedures are listed to help identify a cause for the ALTE. The most
      frequent problems associated with an ALTE are digestive (about 50%), neurological
      (30%), respiratory (20%), cardiovascular (5%), metabolic and endocrine (under
      5%), or diverse other problems, including child abuse. Up to 50% of ALTEs remain
      unexplained. The finding of medical or surgical anomalies leads to specific
      treatments. Surveillance programmes with the use of home monitoring devices may
      be undertaken, preferably with cardiorespiratory monitors, and when possible,
      with event monitors, although no currently available home monitoring device is
      free of false alarms or offers complete protection. Long-term follow-up
      programmes of infants with an apparent life-threatening event contribute to adapt
      medical attitudes to the child's needs and to confirm the medical diagnosis.
      CONCLUSION: a systematic diagnostic evaluation, together with a comprehensive
      treatment programme, increases survival and quality of life for most affected
      infants.

PMID- 14652749
TI  - A boy with breathlessness, digital clubbing and central cyanosis.

PMID- 14652751
TI  - Microsatellite instability analysis and/or immunostaining for the diagnosis of
      hereditary nonpolyposis colorectal cancer?
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) represents 2-4% of colorectal
      cancers and is caused by a constitutional defect in a mismatch repair (MMR) gene,
      most commonly affecting the genes MLH1, MSH2, and MSH6. The MMR defect results in
      an increased cancer risk with the greatest lifetime risks for colorectal cancer
      and endometrial cancer. The HNPCC-associated tumor phenotype is generally
      characterized by microsatellite instability (MSI) and immunohistochemical loss of
      expression of the affected MMR protein. We have evaluated the information
      obtained from MSI analysis and immunostaining for MLH1, MSH2, and MSH6 in a
      series of 128 tumors from patients suspected of having HNPCC. A MSI-high pattern
      was present in 59 of 128 (46%) tumors. Loss of immunohistochemical expression for
      at least one of these MMR proteins was found in 54 of 59 (92%) evaluable MSI
      tumors. This loss affected MLH1 in 28, MSH2 in 22, and MSH6 in 21 tumors (with
      MSH6 as the only loss in 4 tumors). Five (8%) MSI-high tumors showed normal MMR
      protein expression. All 69 microsatellite stable or MSI-low tumors showed normal
      immunostaining for all three proteins. In 28 patients, all with MSI-H tumors,
      germ-line mutations of MLH1, MSH2, or MSH6 had been identified, and a
      corresponding immunohistochemical loss of MMR protein expression was identified
      in all these cases. In summary, immunostaining for the MMR proteins MLH1, MSH2,
      and MSH6 had a sensitivity of 92% and a specificity of 100% for detecting MMR
      deficient tumors. MMR protein immunostaining facilitates mutation analysis in
      suspected HNPCC patients, since it pinpoints the mutated gene, but until the
      genetic background to the MSI tumors with retained MMR protein expression has
      been clarified, we suggest that MSI and MMR protein immunostaining should
      optimally be combined in clinical HNPCC analysis.

PMID- 14652752
TI  - Histopathology training in Europe: a lesson for other specialties?
AB  - Critical shortages of trained histopathologists limit the capacity of cancer and
      other clinical services. A survey of histopathology training in 18 European
      countries conducted by the European Union of Medical Specialists Section of
      Pathology/European Board of Pathology revealed a considerable shortage of both
      trained and trainee histopathologists in several of the responding countries.
      Demographic data indicate a high preponderance of trained histopathologists over
      55 years of age and a notable proportion of part-time personnel. Although the
      training capacity in some countries has been increased, the immediate future of
      histopathology and the clinical services dependent on the specialty is worrisome.
      The histopathology workload is growing, and, in some countries, recruitment of
      trainees is insufficient for future needs. To avert the serious consequences for
      dependent clinical specialties and their patients, there should be a concerted
      European action to promote and expand histopathology training.

PMID- 14652753
TI  - Extensive cerebral metastases from neuroendocrine carcinoma of the prostate.

PMID- 14652754
TI  - Vitamin D3 modulation of plasminogen activator inhibitor type-1 in human breast
      carcinomas under organ culture.
AB  - Urokinase plasminogen activator (uPA), its cell-bound receptor (uPAR) and its
      main inhibitor plasminogen activator type 1 (PAI-1) are present primarily in
      stromal cells in invasive breast carcinoma. The purpose of this study was to
      investigate the regulation by 1,25 dihydroxyvitamin-D3 (VD3) of these invasion
      associated markers expressed in breast cancer tumors under organ culture, which
      preserves the interacting network of tumor and stromal cells. Breast carcinoma
      slices (30 cases), obtained using the Krumdieck tissue slicer, cultured for 48 h
      in the presence or absence of 100 nM vitamin D3, were embedded in formalin-fixed
      paraffin. uPA, uPAR, PAI-1 and VD3 receptor (VDR) were analyzed by
      immunohistochemistry, and their expression, detected in tumor cells and
      fibroblasts of the specimens, was not statistically changed by culture
      conditions. The proportion of cases expressing uPA, uPAR and PAI-1 was not
      affected by VD3 in epithelial cells, but the fraction of cases displaying strong
      PAI-1 reactivity in fibroblasts was reduced ( P=0.016) compared with control
      slices. Fibroblasts isolated from invasive ductal carcinomas and from normal
      breast tissues expressed higher VDR mRNA levels than epithelial cells. In
      cultured tumor fibroblasts, PAI-1 immunostaining and mRNA levels were reduced by
      VD3-limiting fibroblast contribution to invasion.

PMID- 14652756
TI  - The role of action effects in infants' action control.
AB  - In adults, the selection and the planning of actions are influenced by the
      anticipation of desired action effects. However, the role of action effects for
      action control in infants is still an unresolved issue. One important
      prerequisite for infants' action control is that infants are able to relate
      certain movements to certain effects. To test this assumption, it was
      investigated how infants' action control is affected by action effects. By
      applying an imitation paradigm, we studied 12- and 18-month-old infants who first
      observed an adult experimenter demonstrating a three-step action sequence on a
      toy bear. In three experimental groups, the second action step, the third action
      step, or no action step elicited an arbitrary sound as an additional acoustic
      action effect. It was coded how often each of the target actions was performed by
      the infant in a subsequent 90-s test phase. As predicted, the frequency of the
      infant's target action varied depending on which action step elicited the action
      effect. In both age groups, the target action that was combined with an
      acoustical effect was not only produced more often but also occurred with lower
      latency and was in most cases the first target action shown by the infants. These
      results are interpreted as evidence of the important role of action effects in
      infants' action control.

PMID- 14652757
TI  - Pistillody is caused by alterations to the class-B MADS-box gene expression
      pattern in alloplasmic wheats.
AB  - Class-B floral homeotic genes are involved in specifying petal and stamen
      identity during flower development in plant species. Homeotic transformation of
      stamens into pistil-like structures (called pistillody) has been observed in
      alloplasmic lines of bread wheat ( Triticum aestivum L.) having the cytoplasm of
      a wild relative species, Aegilops crassa Boiss. To obtain information about the
      molecular mechanism underlying pistillody induction, we isolated two PISTILLATA (
      PI)-type class-B MADS-box genes, WPI1 ( wheat PI STILLATA # 1) and WPI2, from
      wheat. Phylogenetic reconstruction indicated that WPI1 is orthologous to OsMADS4
      and that WPI2 is probably an ortholog of OsMADS2. Both OsMADS4 and OsMADS2 genes
      were suggested to be PI orthologs in rice, and the function of OsMADS4 as a class
      B gene was proven by the transgenic study. An in situ hybridization study
      demonstrated that the WPI1 gene is expressed in primordia of lodicules and
      stamens in developing florets in wheat. In the alloplasmic wheat line exhibiting
      pistillody, the WPI1 transcripts were not detected in the primordia of pistil
      like stamens, whereas WPI1 was expressed in the lodicules. The wheat APETALA3 (
      AP3)-type class-B MADS-box gene WAP3 ( wheat AP3) /TaMADS#82 showed an expression
      pattern similar to that of WPI1. These results suggest that pistillody in
      alloplasmic wheats is caused by alterations to the expression pattern of class-B
      MADS-box genes.

PMID- 14652758
TI  - Regulation of alpha-galactosidase gene expression in primary foliage leaves of
      barley ( Hordeum vulgare L) during dark-induced senescence.
AB  - alpha-Galactosidase activity (alpha- d-galactoside galactohydrolase, EC 3.2.1.22)
      increased during dark-induced senescence in primary foliage leaves of barley (
      Hordeum vulgare L. cv. Steffi). The changes in activity were accompanied by
      parallel changes in expression of the HvSF11 gene encoding a putative alpha
      galactosidase. The transcript level of HvSF23 encoding a second putative alpha
      galactosidase stayed constant during leaf senescence. Both alpha-galactosidase
      activity and the level of the HvSF11 transcript decreased after exogenous
      application of sucrose and glucose to detached dark-incubated leaves. In
      contrast, the HvSF23 transcript level was not influenced by sugars. Application
      of glucose analogs to detached and dark-incubated leaves revealed that
      phosphorylation of hexose by hexokinase modulates both the alpha-galactosidase
      activity and the expression of HvSF11. These results indicate that the expression
      of the genes coding for two alpha-galactosidase isoenzymes is regulated by
      different signalling pathways, suggesting different functions for the two gene
      products.

PMID- 14652759
TI  - Subcellular localization and topology of beta(1-->4)galactosyltransferase that
      elongates beta(1-->4)galactan side chains in rhamnogalacturonan I in potato.
AB  - The subcellular localization and topology of rhamnogalacturonan I (RG-I) beta(1-
      >4)galactosyltransferase(s) (beta[1-->4]GalTs) from potato ( Solanum tuberosum
      L.) were investigated. Using two-step discontinuous sucrose step gradients,
      galactosyltransferase (GalT) activity that synthesized 70%-methanol-insoluble
      products from UDP-[(14)C]Gal was detected in both the 0.5 M sucrose fraction and
      the 0.25/1.1 M sucrose interface. The former fraction contained mainly soluble
      proteins and the latter was enriched in Golgi vesicles that contained most of the
      UDPase activity, a Golgi marker. By gel-filtration analysis, products of 180-2000
      Da were found in the soluble fraction, whereas in the Golgi-enriched fraction the
      products were larger than 80 kDa and could be digested with rhamnogalacturonan
      lyase and beta(1,4) endogalactanase to yield smaller rhamnogalacturonan
      oligomers, galactobiose and galactose. The endogalactanase requires beta(1-
      >4)galactans with at least three galactosyl residues for cleavage, indicating
      that the enzyme(s) present in the 0.25/1.1 M Suc interface transferred one or
      more galactosyl residues to pre-existing beta(1-->4)galactans producing RG-I side
      chains in total longer than a trimer. Thus, the beta(1-->4)GalT activity that
      elongates beta(1-->4)-linked galactan on RG-I was located in the Golgi apparatus.
      This beta(1-->4)GalT activity was not reduced after treatment of the Golgi
      vesicles with proteinase, but approximately 75% of the activity was lost after
      treatment with proteinase in the presence of Triton X-100. In addition, the
      beta(1-->4)GalT activity was recovered in the detergent phase after treatment of
      Golgi vesicles with Triton X-114. Taken together, these observations supported
      the view that the RG-I beta(1-->4)GalT that elongates beta(1-->4)galactan was
      mainly located in the Golgi apparatus and integrated into the membrane with its
      catalytic site facing the lumen.

PMID- 14652760
TI  - Ca(2+) influx through the basolateral- and luminal membranes of colonic
      epithelium in neonatal rats.
AB  - In this study, the short-circuit currents ( I(sc)) of electrolyte absorption and
      secretion in neonatal and adult rat colonic mucosa were compared and the role of
      Ca(2+) influx through luminal membranes examined in relation to the replenishment
      of intracellular Ca(2+) stores in colonic crypt cells. Neonatal tissues displayed
      higher amiloride-sensitive I(sc) and larger increases of electrogenic Cl(-)
      secretion in response to an increase in cytosolic [Ca(2+)] ([Ca(2+)](c)) or cAMP
      than found in adult colonic epithelium. Ca(2+)-mediated Cl(-) secretion as
      reflected in the I(sc) responses to carbachol ( I(sc,CCh)) showed milder "run
      down" in neonates than in adult rats. We then employed the relatively stable
      I(sc,CCh) of the neonatal colon to investigate the polarity of Ca(2+) entry
      pathway after muscarinic stimulation. Repetitive stimulation with CCh under
      Ca(2+)-free conditions emptied the intracellular Ca(2+) stores and abolished the
      I(sc,CCh). Re-adding Ca(2+) to the basolateral perfusate rapidly restored
      I(sc,CCh) (about 71% of control in 10 min). In contrast, after re-adding Ca(2+)
      to the luminal perfusate only, the recovery of I(sc,CCh) took much longer and was
      incomplete, recovering to only 28% of control after 30 min. Recovery was
      accelerated by increasing [Ca(2+)] in the luminal perfusate (5 mM) and blocked by
      the presence of Gd(3+) (100 microM) in the luminal perfusate. The above results
      suggest that, in addition to the predominant role of Ca(2+) entry through the
      basolateral membrane, the influx of Ca(2+) through luminal membranes might also
      play a role in the Ca(2+) homeostasis of colonic epithelial cells.

PMID- 14652761
TI  - Reproducibility of the exponential rise technique of CO(2) rebreathing for
      measuring P(v)CO(2) and C(v)CO(2 )to non-invasively estimate cardiac output
      during incremental, maximal treadmill exercise.
AB  - The purpose of this study was to determine the reproducibility of the indirect
      Fick method for the measurement of mixed venous carbon dioxide partial pressure
      (P(v)CO(2)) and venous carbon dioxide content (C(v)CO(2)) for estimation of
      cardiac output (Q(c)), using the exponential rise method of carbon dioxide
      rebreathing, during non-steady-state treadmill exercise. Ten healthy participants
      (eight female and two male) performed three incremental, maximal exercise
      treadmill tests to exhaustion within 1 week. Non-invasive Q(c) measurements were
      evaluated at rest, during each 3-min stage, and at peak exercise, across three
      identical treadmill tests, using the exponential rise technique for measuring
      mixed venous PCO(2) and CCO(2) and estimating venous-arterio carbon dioxide
      content difference (C(v-a)CO(2)). Measurements were divided into measured or
      estimated variables [heart rate (HR), oxygen consumption (VO(2)), volume of
      expired carbon dioxide (VCO(2)), end-tidal carbon dioxide (P(ET)CO(2)), arterial
      carbon dioxide partial pressure (P(a)CO(2)), venous carbon dioxide partial
      pressure ( P(v)CO(2)), and C(v-a)CO(2)] and cardiorespiratory variables derived
      from the measured variables [Q(c), stroke volume (V(s)), and arteriovenous oxygen
      difference ( C(a-v)O(2))]. In general, the derived cardiorespiratory variables
      demonstrated acceptable (R=0.61) to high (R>0.80) reproducibility, especially at
      higher intensities and peak exercise. Measured variables, excluding P(a)CO(2) and
      C(v-a)CO(2), also demonstrated acceptable (R=0.6 to 0.79) to high reliability.
      The current study demonstrated acceptable to high reproducibility of the
      exponential rise indirect Fick method in measurement of mixed venous PCO(2) and
      CCO(2) for estimation of Q(c) during incremental treadmill exercise testing,
      especially at high-intensity and peak exercise.

PMID- 14652762
TI  - Differences in the energy cost between children and adults during front crawl
      swimming.
AB  - There is little information available about the swimming economy of children. The
      aim of this study was to examine any possible differences in swimming economy in
      children and adults, swimming front crawl submaximally. Swimming economy was
      compared in adults [ n=13, aged 21.4 (3.7) years] and children [n=10, aged 11.8
      (0.8) years] tested at four submaximal 6-min workloads. Oxygen consumption (VO2)
      was measured with Douglas bags in a 25-m pool and pacer lights were used to
      control the velocities. Swimming economy was scaled to body size using mass (BM),
      body surface area (BSA) and body length (BL). Children had lower VO2 (litres per
      minute) at a given velocity than the adults, with 1.86 (0.28) and 2.39 (0.20) l
      min(-1) respectively (at 1.00 m s(-1)). When scaling for size, children had
      higher VO2 measured in litres per square metre per minute and millilitres per
      kilogram per minute (divided by BSA and BM) than adults. The VO2 divided by BL
      was found not to differ between the two groups. The O2 cost of swimming 1 m at a
      velocity of 1.00 m s(-1) was lower in the children [31.0 (4.6) ml m(-1)] than in
      the adults [39.9 (3.3) ml m(-1) P<0.01], probably due to a lower total drag in
      the children. The results also showed that for children a relationship between
      swimming velocity cubed and VO2 exists as shown earlier for adults. It is
      concluded that, when scaling for BSA and BM, children are less economical than
      adults, when scaling for BL, children are equally economical, and when
      considering energy cost per metre and absolute VO2, children are more economical
      than the adults.

PMID- 14652763
TI  - Peak exercise oxygen uptake and left ventricular systolic and diastolic function
      and arterial mechanics in healthy young men.
AB  - Echocardiography can be used to estimate myocardial contractility by the
      assessment of the circumferential end-systolic stress-corrected left ventricular
      (LV) fractional shortening measured at midwall level (stress-corrected MWS).
      Whether stress-corrected MWS at rest predicts exercise peak oxygen uptake (peak
      VO(2)) is unknown. Also, it is not known whether the propagation rate of the
      early LV filling wave (E wave propagation rate, V(p)), a new pre-load insensitive
      index of LV diastolic function, and echocardiographically assessed indices of
      arterial stiffness correlate to peak VO(2). Accordingly, we performed
      echocardiographic studies and exercise tests with respiratory gas analysis in 15
      young healthy male subjects (mean age 27 years, range 18-36). Neither stress
      corrected-MWS ( r=0.20, P=NS) nor ejection fraction ( r=-0.05, P=NS) correlated
      significantly with peak VO(2). Adjustment for age and resting heart rate had no
      effect on the results. In separate multiple regression models adjusting for
      standard covariates (age, LV size and heart rate), peak VO(2) correlated with
      V(p) (beta=0.98, P<0.01), as well as with E/A (beta=0.85, P<0.01), and with the
      isovolumic relaxation time (indicator of LV relaxation) (beta=-0.59, P<0.05).
      Arterial stiffness indices showed no significant relation to peak VO(2). We
      conclude that in young healthy male subjects, resting myocardial contractility
      and arterial stiffness are not significant correlates of peak VO(2), whereas LV
      diastolic function, and in particular V(p), influences the variability of peak
      VO(2).

PMID- 14652764
TI  - Phosphatidylinositol-dependent bond between alkaline phosphatase and collagen
      fibers in the periodontal ligament of rat molars.
AB  - Alkaline phosphatase (ALP) is anchored to the outer leaflet of the lipid bilayer
      via phosphatidylinositol (PI) and ALP activity has been localized in the plasma
      membrane of numerous tissues. In the periodontal ligament ALP activity is found
      in the collagen fibers in addition to the plasma membrane of the osteoblasts and
      fibroblasts. In this study, we examined the distribution of ALP activity in the
      periodontal ligament of rat molars and also examined whether the bond between ALP
      and collagen fibers is dependent on PI by using phosphatidylinositol-specific
      phospholipase C (PI-PLC). ALP activity was distributed in the periodontal
      ligament. The activity mirrored the distribution of collagen fibers in the
      periodontal ligament. Cytochemical analysis also demonstrated that ALP activity
      was located not only in the plasma membrane of fibroblasts, but also in the
      collagen fiber bundles and fibrils in the periodontal ligament. After treatment
      with PI-PLC, the loss of ALP activity in the periodontal ligament was observed
      histochemically, and the loss of ALP activity in the fibroblasts as well as in
      the collagen fiber bundles and fibrils was observed cytochemically. These results
      strongly indicate that the bond between ALP and the collagen fibers is also
      dependent on PI.

PMID- 14652765
TI  - Effects of a new dexamethasone-delivery system (Surodex) on experimental
      intraocular inflammation models.
AB  - BACKGROUND: To investigate the effects of a new biodegradable dexamethasone drug
      delivery system, Surodex, in two experimental intraocular inflammation models;
      endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU).
      METHODS: Surodex was inserted into the right anterior chambers (ACs) of rats. In
      the EIU experiment, protein concentration, cell infiltration, and myeloperoxidase
      (MPO) activity in the aqueous humor were measured 24 h after injection. Eyes were
      evaluated histopathologically. In the EAU experiment, firstly, Surodex was
      administered at various days after immunization. Then, Surodex was administered
      on day 9 and eyes were evaluated histopathologically. Intraocular cytokine levels
      (IFN-gamma and IL-4) were investigated. RESULTS: In the EIU experiments, eyes
      with Surodex exhibited significantly reduced inflammation compared with
      contralateral controls. Protein concentrations, cell infiltrations, as well as
      MPO activity were reduced. In the EAU experiments, all rats with Surodex given on
      days 0 or 7 showed no or significantly reduced inflammation in both eyes. Rats
      treated on day 12 developed reduced inflammation only in the treated eyes. IFN
      gamma levels were significantly lower in the eyes with Surodex, whereas IL-4 was
      not detectable. CONCLUSIONS: This new, biodegradable corticosteroid drug-delivery
      system is highly effective in suppressing intraocular inflammation, and should be
      a useful tool to manage uveitis in humans.

PMID- 14652766
TI  - Indocyanine green-assisted vitreomacular surgery: adverse effects.

PMID- 14652767
TI  - Phakomatous choristoma of the eyelid.
AB  - BACKGROUND: We report a case of a phakomatous choristoma of the lower eyelid.
      METHODS: A subcutaneous tumor was excised from the eyelid. RESULTS: A 12-month
      old girl was referred because of a tumor in her right lower eyelid, which had
      been present since birth. The subcutaneous tumor had remained unchanged and was
      considered a dermoid cyst. No other abnormalities were present. The tumor was
      excised. Histologically, the tumor consisted of abnormal lens tissue. The
      immunohistochemical profile included strong immunoreactivity for vimentin and S
      100. CONCLUSION: Phakomatous choristoma is an extraordinary rare tumor that
      probably develops from an abnormal separation or migration of cells from the lens
      placode into the mesodermal structures of the lid. Only 18 cases have been
      described so far, less than 5 in the European literature. This benign tumor may
      be confused with cutaneous adnexal neoplasms.

PMID- 14652768
TI  - Coats-like lesions in Usher syndrome type II.
AB  - BACKGROUND: An unusual case of Usher syndrome type II associated with bilateral
      Coats-like exudative retinopathy is described. METHODS: A 14-year-old boy with
      congenital sensorineural deafness and normal vestibular functions presented with
      a recent history of night blindness. He was followed for 3 years with fundus
      photography, intravenous fluorescein angiography, electroretinography and
      audiometric testings. His parents refused any form of treatment. RESULTS:
      Fundoscopy showed bilateral retinitis pigmentosa and a single focus of subretinal
      exudation and overlying telangiectatic retinal vessels inferotemporal to the
      vascular arcade in the right eye. He had bilateral mild macular edema. A year
      later, a similar lesion developed inferotemporally in the left fundus.
      Electroretinography responses, particularly the rod-mediated signals, were
      significantly reduced. Audiometric studies documented hearing loss in high
      frequencies. His visual acuity declined from 20/40 to 20/80 RE and from 20/80 to
      20/100 LE during follow-up. No new lesions developed. CONCLUSIONS: Coats-type
      exudative lesions may develop in patients with Usher syndrome type II. Although
      left untreated, only a minimal increase in exudation occurred over 3 years.

PMID- 14652769
TI  - Numerical simulation of airflow in the human nose.
AB  - Unobstructed air passageways as well as sufficient contact of the air stream with
      the mucous membrane are essential for the correct function of the nose. For that,
      local flow phenomena, which often cannot be captured by standard diagnostic
      methods, are important. We developed and validated a method for the numerical
      simulation of the nasal airflow. Two anatomically correct, transparent resin
      models of human nasal cavities, manufactured by a special casting technology, and
      the nasal cavities of two patients were reconstructed as Computer Aided Design
      models based on computed tomography (CT) scans. One of the nasal models and one
      clinical case represented a normal nasal anatomy, while the others were examples
      of pathological alterations. The velocity and pressure fields in these
      reconstructed cavities were calculated for the entire range of physiological
      nasal inspiration using commercially available computational fluid dynamics
      software. To validate the results rhinoresistometric data were measured and
      characteristic streamlines were videotaped for the resin models. The numerical
      results were in good agreement with the experimental data for the investigated
      cases. An example of a complex clinical case demonstrates the potential benefit
      of the developed simulation method for rhinosurgical planning. The results
      support the assumption that even under the specific conditions of the clinical
      practice the application of numerical simulation of nasal airflow phenomena may
      become realistic in the near future. However, important technical issues such as
      a completely automated reconstruction of the nasal cavity still need to be
      resolved before such simulations are efficient and cost effective enough to
      become a standard tool for the rhinologist.

PMID- 14652770
TI  - Pediatric lobular capillary hemangioma of the nasal cavity.
AB  - Lobular capillary hemangioma (LCH), also called pyogenic granuloma, is a benign
      vascular tumor that is pedunculated on the skin and the mucous membranes of the
      oral cavity. This disease occurs in all ages, but more often in the 3rd decade,
      and is seen in females more than males. LCH commonly appears in early childhood
      and affects males more than females in the pediatric age group. The gingiva,
      lips, tongue and buccal mucosa are the most common sites of mucosal LCH, but the
      nasal cavity is rare. Micro-trauma and hormonal factors are the most common
      etiologic factors. Epistaxis and nasal obstruction are the most marked symptoms.
      We describe the case of a 6-year-old girl with intra-nasal lobular capillary
      hemangioma presented with epistaxis and nasal obstruction. This should be
      considered in the differential diagnosis of childhood endonasal masses with
      bleeding. Total excision using endoscopic technique is the treatment of choice.

PMID- 14652771
TI  - Thyroid abscess--an acute emergency.
AB  - An abscess in a long-standing goitre is usually life threatening. A patient with
      a large goitre was lost to follow-up for about 10 years and presented with a
      large thyroid abscess causing acute respiratory obstruction. The abscess caused
      erosion of the tracheal wall and perforation of the esophagus. Clostridium
      septicum was the causative organism, which is almost always associated with
      cancer of the colon. This led to the detection of colonic malignancy in this
      patient on further investigations. We describe the complications of a thyroid
      abscess and discuss the pathophysiology and treatment.

PMID- 14652772
TI  - Hyperpneumatization of the temporal, occipital and parietal bones.
AB  - Hyperpneumatization of the temporal bone with extension into the occipital bone
      and even the parietal bones is a rare condition. According to a review of the
      literature, it mostly appears unilaterally in men and on the right side. Often it
      is discovered when complications like pneumatocele or pneumocephalus appear. The
      authors review and analyze all reported cases of hyperpneumatization, its
      symptoms, complications and treatment. We present a patient with extensive
      pneumatization found in the mastoid process, temporal bone, occipital bone and
      both parietal bones, who was discovered accidentally. The cause of the extension
      of pneumatization into the occipital and parietal bone is probably incomplete
      closure of the occipitomastoid synchondrosis and lambdoid and sagital sutures,
      which usually close in early adulthood and later, even in the 30s. Asymptomatic
      patients should be aware of possible complications, and in case of complications,
      operative therapy is often indicated.

PMID- 14652774
TI  - Lymphocyte immunotherapy and its probable mechanism in the maintenance of
      pregnancy in women with recurrent spontaneous abortion.
AB  - INTRODUCTION: Most women with alloimmune cause of recurrent spontaneous abortion
      (RSA) includes increased sharing of human leukocyte antigens (HLA) that may
      prohibit the mother from making anti-paternal cyto-toxic antibodies (APCA), anti
      idiotypic antibodies (Ab2) and mixed lymphocyte reaction blocking antibodies (MLR
      Bf). Overactivity of T helper-1 (Th-1) cytokines and natural killer (NK) cells
      have been also reported to be the major alloimmune cause of recurrent spontaneous
      abortion (RSA). It was revealed from extensive updated analysis of this subject
      that paternal lymphocytes immunotherapy may play a significant role in the
      prevention of alloimmune cause of fetal loss in women with RSA. These alloimmune
      parameters are found to be suppressed in successful immunotherapy, which is
      comparable to normal pregnancy. REVIEW AND DISCUSSION: Various studies
      represented that paternal lymphocyte immunotherapy was attributed to the high
      expression of APCA, Ab2, MLR-Bf and inhibition of Th-1 pattern of cytokines and
      NK cell activity in women with alloimmune cause of RSA. Present updated
      randomized clinical trials demonstrated that women with RSA of study group who
      have been treated with paternal lymphocyte immunotherapy had more successful
      outcomes (68%) as compared to women with RSA of control group who either received
      autologous lymphocytes/third party lymphocytes/normal saline or no therapy (54%),
      ( p<0.02). However, when the results of the randomized and nonrandomized studies
      were pooled together it was observed that 67% of women with RSA of study group
      who received paternal lymphocyte immunotherapy showed successful pregnancy
      outcome in comparison to 36% success in women with RSA of control group who
      either received autologous lymphocytes/third party lymphocytes/normal saline or
      no therapy ( p<0.05). CONCLUSION: These results advocate the role of paternal
      lymphocyte immunotherapy for the maintenance of pregnancy in women with RSA.

PMID- 14652775
TI  - Indication of fibroblast apoptosis during the maturation of disc-shaped
      mechanically stressed collagen lattices.
AB  - Human dermal fibroblasts seeded in tense disc-shaped collagen gels organized
      gradually into a tissue composed of three distinct superimposed layers of cells:
      a basal layer of aligned myofibroblasts, a middle layer of unoriented
      fibroblasts, and an upper layer of myofibroblasts oriented orthogonally to the
      basal myofibroblasts. Confocal observation of alpha-smooth muscle actin (alpha
      SMA) immunolabelling as a marker of myofibroblasts showed that the upper
      myofibroblasts disappeared during maturation of the lattices. Observation of
      morphological modifications of cells, typical chromatin condensation identified
      by Hoechst 33258 staining, and detection of ssDNA after formamide-induced
      denaturation suggested the involvement of apoptosis in myofibroblast
      disappearance. It is suggested that the model of disc-shaped stressed collagen
      lattice is thus able to mimic conditions in wound repair: on the one hand, wound
      contraction during which fibroblasts undergo mechanical stress and, on the other,
      apoptotic disappearance of cells at the end of tissue retraction.

PMID- 14652776
TI  - Neurilemoma located at the patellar insertion of vastus medialis obliquus.
AB  - We report a case of a rare neurological tumour arising in the knee joint with no
      apparent connection to the major nerve trunks in the area. After the patient
      failed to improve through rehabilitation, surgery was performed, revealing a
      concomitant tear of the medial meniscus as well as a mass which was excised
      through an external supero-medial incision into the knee. Histopathological
      analysis later confirmed the diagnosis of a neurilemoma.

PMID- 14652777
TI  - Treatment of early cut-out of a lag screw using a trochanter supporting plate: 11
      consecutive patients with unstable intertrochanteric fractures.
AB  - INTRODUCTION: Superior cut-out of a lag screw remains a serious complication in
      the treatment of intertrochanteric fractures. It is related to the stability of
      fracture reduction. We describe the application of a trochanter supporting plate
      (TSP) to restore the fracture stability after early cut-out of a lag screw in
      unstable intertrochanteric fractures. MATERIALS AND METHODS: A total of 11
      consecutive patients with superior cut-out of the lag screw of a dynamic hip
      screw (DHS) or a gamma nail in an unstable intertrochanteric fracture occurring
      within 6 months after surgery were included in the present study. They underwent
      repeat surgery for placement of a DHS and a laterally mounted TSP of our design.
      All patients were monitored for at least 6 months (median 15 months; range 6-28
      months). RESULTS: There was no repeated cut-out of a lag screw, and 10 patients
      (91%) achieved bony union within 5 months. At the last follow-up, all patients
      could walk with or without aids. CONCLUSION: It reveals that a TSP, as an
      adjuvant to a lag screw placed inferiorly, is an easy and safe solution for the
      treatment of early cut-out of a lag screw in unstable intertrochanteric
      fractures.

PMID- 14652778
TI  - Treatment of humeral shaft nonunions: nailing versus plating.
AB  - INTRODUCTION: The aim of this study was to compare plating and nailing for
      treating nonunions of the upper two-thirds of the humerus. MATERIALS AND METHODS:
      Fifty nonunions of the upper two-thirds of the humerus were treated by two
      different methods: 24 of them by unreamed locked nailing and bone graft (group
      A), and the other 26 by plate fixation and bone grafting (group B). RESULTS: All
      fractures healed in both groups. In group A, the time required for healing was
      4.2 months (range 4-6 months), whereas in group B it was 4.7 months (range 4-6
      months). This difference was statistically significant ( p<0.05). Functional
      results and the range of motion of the shoulder and elbow were similar with both
      techniques. In group B there were 3 cases of transient, iatrogenic, radial nerve
      palsy. CONCLUSIONS: We feel that both plate fixation and the unreamed humeral
      locked nail are good alternatives for the treatment of humeral shaft nonunions,
      although nailing achieves union earlier and has fewer complications.

PMID- 14652779
TI  - Periprosthetic acetabular bone loss using a constrained acetabular component.
AB  - We describe two patients with a constrained acetabular component who required
      treatment for recurrent dislocation showing postoperative periprosthetic
      acetabular bone loss. These hips required revision surgery and demonstrated
      considerable bone loss caused by the migrated acetabular component. Impingement
      may have occurred with increased stress at the bone-prosthesis interface, and the
      sharp ends of screws with a metal shell may have gradually plowed up the
      acetabular bone. These failures illustrate the potential risk of using a
      constrained acetabular component.

PMID- 14652780
TI  - Multiple supratentorial epidural haematomas after posterior fossa surgery.
AB  - Postoperative epidural haematoma distant to a site of craniotomy is a rare but
      possibly hazardous complication. We report a 31-year-old female who presented
      with a history of chronic hydrocephalus due to fourth-ventricular plexus
      papilloma. Following resection of the posterior fossa tumour with intraoperative
      placement of a ventricular drainage, she consecutively developed four
      supratentorial epidural haematomas at different locations, all necessitating
      evacuation. The clinical manifestations ranged from subtle neurological deficits
      to signs of tentorial herniation; the ultimate outcome was complete recovery.
      Rapid tapering of CSF pressure after long-standing hydrocephalus and clotting
      disorders could be implicated as causative factors. We stress the importance of
      early postoperative CT scan and optimal management of ventricular pressure and
      coagulation status to detect and prevent this possibly life-threatening
      complication.

PMID- 14652781
TI  - Multicentre study of the molecular epidemiology, serotypes and antimicrobial
      susceptibility patterns of invasive Streptococcus pneumoniae invasive isolated
      from children in the Ille de France area.
AB  - Between January 1997 and April 2002, 73 consecutive invasive strains of
      Streptococcus pneumoniae were isolated from children under 16 years of age in
      four hospitals in suburban Paris. Their genetic diversity was investigated by
      serotyping and analysis of pulsed-field gel electrophoresis restriction patterns.
      Antibiotic susceptibility patterns were analysed by disk susceptibility testing
      and determination of minimal inhibitory concentrations. The genetic basis of
      macrolide resistance was investigated by polymerase chain reaction. Studies of
      penicillin and vancomycin tolerance were performed for each strain. Despite the
      high prevalence (45.2%) of penicillin-nonsusceptible Streptococcus pneumoniae,
      resistance to amoxicillin (1.4%) was rare, and no strain was resistant to
      cefotaxime. Overall, 4.1% of pneumococcal strains were resistant to penicillin.
      Penicillin or vancomycin tolerance was not detected in any of the 73 strains
      studied. Of the erythromycin-resistant strains (48%), all but one carried the
      ermB gene. No strains showing a decreased susceptibility to ciprofloxacin (MIC,
      >4 mg/l) or overexpressing an efflux pump inhibited by reserpine were isolated.
      The serotypes found, in order of frequency, were as follows: 18C, 14, 6B, 19F,
      19A, 9V, 23F, 1, 7F, 9A, 38. Strains of penicillin-nonsusceptible Streptococcus
      pneumoniae belonged predominantly to serotypes 14, 6B, 9V, 9A, 23F, 19F and 19A.
      The seven-valent conjugated vaccine covered 85.5% of the serogroups isolated in
      children under 2 years of age and 65.6% of the serogroups identified in children
      over 2 years of age. The genetic analysis showed a high identity for some
      serotypes, such as 14/9V, 6B and 23F. The use of the seven-valent conjugated
      vaccine is a critical measure to prevent invasive pneumococci infections in
      children in the Ille de France area.

PMID- 14652782
TI  - Obvious lack of association between dynamics of epidemic methicillin-resistant
      Staphylococcus aureus in central Europe and agr specificity groups.
AB  - During the past 8 years, changes in the prevalence and spread of different
      epidemic methicillin-resistant Staphylococcus aureus (MRSA) have been observed in
      central Europe, with the emergence of new strains possessing fewer resistance
      characters. This has also been demonstrated at the level of particular hospitals.
      Since variation in agr specificity type has been proposed as a possible reason
      for population dynamics in Staphylococcus aureus, the agr specificity groups of
      different epidemic MRSA strains were investigated by PCR using agr group-specific
      primers. Four of the "old" as well as two "new" epidemic strains exhibited agr
      specificity group I. One group of epidemic MRSA strains, which has been observed
      since the beginning of the 1990s, exhibited the agr specificity group II.
      Sequencing the variable part ( agrB-D-C) of the agr locus revealed only six
      relevant nucleotide changes within this region, with three of them modifying the
      Shine-Dalgarno sequence region of agrC. On the basis of the results obtained, it
      is proposed that the dynamics observed in the population of MRSA in Germany is
      not due to different agr group specificities in "old" and "new" epidemic clones.

PMID- 14652783
TI  - Impairment of respiratory burst in polymorphonuclear leukocytes by extended
      spectrum beta-lactamase-producing strains of Klebsiella pneumoniae.
AB  - The ability of extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL
      producing Klebsiella pneumoniae strains to induce a respiratory burst in
      polymorphonuclear leukocytes (PMNLs) was investigated. Ninety ESBL-producing and
      178 non-ESBL-producing Klebsiella pneumoniae isolates were serotyped and their
      ability to induce a respiratory burst in PMNLs tested by monitoring the cells'
      chemiluminescence (CL) response. The percentage of isolates inducing high levels
      of CL response (CL>75%) was significantly higher among non-ESBL producers (52%)
      than among ESBL producers (32.2%) ( P<0.0001; OR=3.396; 95%CI=2.036-5.664). The
      median CL response was significantly higher among the non-ESBL producers (76.9%)
      than among the ESBL producers (52.6%) ( P=0.034). The two groups did not differ
      in their ability to resist intracellular killing by PMNLs ( P>0.05), with strains
      inducing high levels of CL response having significantly lower survival rates
      (31.8% vs. 42.4%) than strains inducing low levels of CL response (164% vs. 200%)
      ( P<0.01). The frequencies of the K2 and the K25 serotypes were significantly
      higher among ESBL-producing strains (17.8% and 22.2%, respectively) than among
      the non-ESBL producers (6.2% and 1.7%, respectively) ( P=0.0057 and P<0.0001). Of
      the 77 Klebsiella K serotypes, 71 were detectable among the non-ESBL producers,
      but only 24 were detectable among the ESBL producers. ESBL-producing Klebsiella
      pneumoniae strains might have a greater pathogenic potential by virtue of their
      ability to escape the phagocytic activity of PMNLs.

PMID- 14652784
TI  - Two cases of systemic Candida glabrata infection following in vitro fertilization
      and embryo transfer.
AB  - Presented here are two cases of systemic Candida glabrata infection diagnosed in
      two expectant mothers and their fetuses at 34 and 22 weeks' gestation. The
      underlying risk factors in case 1 were in vitro fertilization and embryo
      transfer, recurrent yeast vaginitis and two intravenous injections of
      betamethasone. The risk factors in case 2 were in vitro fertilization and embryo
      transfer, recurrent yeast vaginitis, antibiotics for treatment of a urinary tract
      infection due to Morganella morganii and amniocentesis. In both cases, vaginal
      fluid yielded growth of a yeast that was not identified. Candida glabrata was
      isolated from samples obtained from the mothers and their babies. Since Candida
      glabrata lacks hyphae, membranitis and infection of the fetuses were demonstrated
      only on slides stained with Gomori Grocott and periodic acid-Schiff. Both cases
      suggest that for such pregnancies the follow-up of vaginal fluid should include
      the identification of any yeasts grown on selective Candida medium. In case of
      premature rupture of membranes, systematic sampling of mothers and their infants
      or fetuses should be associated with microscopic study of placentas, membranes
      and stillborn fetuses with Gomori Grocott and periodic acid-Schiff staining
      techniques.

PMID- 14652785
TI  - Inflammation and degeneration in multiple sclerosis.
AB  - Multiple (MS) sclerosis is a chronic inflammatory demyelinating disease of the
      central nervous system with the pathological hallmarks of inflammation,
      demyelination, axon loss and gliosis. In the initial relapsing-remitting phase of
      the disease, the inflammatory-demyelinating component seems to predominate,
      whereas the progressive disease appears to be characterized by a
      neurodegenerative component leading to extensive neuroaxonal damage in the MS
      brain. Axon loss most likely determines the persistent neurological deficit in
      progressive MS. Recent studies pointed out that axon damage occurs early in the
      disease and during lesion development. Two different phases of axon degeneration
      were characterized, the first occurring during active myelin breakdown and the
      second in chronic demyelinated plaques in which the naked axon seems more
      susceptible to further damage. The exact mechanisms and effector molecules of
      axonal degeneration, however, are not yet defined, and an axon-protective therapy
      has not yet been established.

PMID- 14652786
TI  - The transition from relapsing-remitting MS to irreversible disability: clinical
      evaluation.
AB  - The development of a progressive course is by far the most deleterious event in
      the case of a multiple sclerosis (MS) patient. It occurs in about 90% of
      relapsing remitting patients by 20-25 years from onset. The clinical transition
      to secondary progressive MS is phenotypically distinctive and both patients and
      physicians acknowledge that a fundamental shift in the degree of responsiveness
      to anti-inflammatory therapies has occurred. This review discusses the clinical
      studies that provided important findings relating to our understanding on
      different mechanisms that may contribute to irreversible disability in MS.

PMID- 14652787
TI  - Biological markers of the inflammatory phase of multiple sclerosis.
AB  - The search for biological markers in multiple sclerosis (MS) has been spoiled by
      the intrinsic nature of the disease that occurs in a secluded organ which cannot
      be accessed by routine sampling. Thus, markers obtained so far from the
      peripheral blood of MS individuals are often of little reproducibility while
      results obtained from the cerebrospinal fluid (CSF) are conveniently linked to
      the disease process but of little utility due to inaccessibility to repeated
      sampling. In this review we briefly discuss the biological markers available to
      date.

PMID- 14652788
TI  - MRI aspects of the "inflammatory phase" of multiple sclerosis.
AB  - In early relapsing-remitting (RR) multiple sclerosis (MS), conventional magnetic
      resonance imaging (MRI) has proved to be a valuable tool to assess disease
      activity over time. However, conventional MRI can only provide gross estimates of
      irreversible tissue damage within and outside such lesions. Other MR-based
      techniques, including magnetization transfer MRI, diffusion-weighted MRI, proton
      MR spectroscopy and functional MRI, have the potential to provide additional
      pieces of information about the nature and the extent of MS tissue damage since
      the early "inflammatory phase" of the disease. The application of these MR
      techniques to the study of early RRMS is likely to improve our understanding of
      the pathophysiology of MS and our ability to assess the efficacy of experimental
      treatments.

PMID- 14652789
TI  - Biological indicators of the neurodegenerative phase of multiple sclerosis.
AB  - The recent re-discovery of axonal damage in multiple sclerosis has led to a
      renewed interest in neurodegenerative mechanisms of the disease. Transected or
      injured axons release several molecules from their proximal extremity into the
      intercellular space. Although these molecules can be measured, however, a
      biological marker of axonal and neuronal degeneration is still lacking.
      Cytoskeleton structural proteins like actin, tubulin, L-neurofilaments and tau
      protein, axon-specific antibodies, other neuronal or glial proteins like S-100,
      14-3-3 and glial fibrillary acid protein, neuronal specific enolase, and nitric
      oxide and its metabolites are some of the putative markers that deserve further
      investigation and validation. At present, none of them fulfils the criteria of
      applicability in clinical practice, and the levels of N-acetylaspartate
      determined by magnetic resonance spectroscopy remain the most reliable measure of
      axonal damage.

PMID- 14652790
TI  - Imaging neuronal and axonal degeneration in multiple sclerosis.
AB  - Neuronal and axonal damage has become an important issue in multiple sclerosis.
      This has been emphasised by recent magnetic resonance imaging (MRI) studies that
      have shown evidence of axonal damage in both lesional and non-lesional white
      matter and in grey matter. In this respect, proton MR spectroscopy (by monitoring
      levels of Nacetylaspartate, a putative marker of axonal integrity) and computed
      measurements of cerebral volumes have been particularly illuminating. Recent
      studies using these MRI measures have demonstrated that cerebral neuro-axonal
      damage begins and contributes to disability from the earliest stages of the
      disease. This implies that the apparently primary role of neuronal pathology in
      the pathogenesis of the disease should be given due importance and argues for the
      early treatment of multiple sclerosis with agents directed not only against
      inflammation, but also towards neuronal protection.

PMID- 14652791
TI  - Physiopathology of multiple sclerosis.
AB  - Pleiotropy and redundancy are distinctive elements of the immune response. Recent
      research into the inflammatory component of multiple sclerosis (MS) indicates
      that, as expected, pleiotropy and redundancy characterize various
      physiopathological mechanisms of the disease. A certain degree of redundancy is
      becoming apparent also as far as the degenerative component is concerned.
      Cumulatively, these data suggest that treatments that target single pathogenetic
      pathways are unlikely to provide a definitive solution. Combination therapies may
      offer, in principle, some advantage, although there is a need for more
      information on the aetiology of the disease.

PMID- 14652792
TI  - Growth factors.
AB  - Recent studies have provided new insights on the identity and mechanisms of
      action of growth factors implicated in myelination processes. Members of several
      different families of growth factors have been shown to affect oligodendrocyte
      survival, proliferation and differentiation and their manipulation in the
      experimental animal provides a means to clarify the molecular mechanisms
      underlying repair processes in the injured central nervous system. A future
      challenge is to use this knowledge to boost remyelination and ameliorate clinical
      symptoms in patients with demyelinating diseases, like multiple sclerosis.

PMID- 14652793
TI  - From inflammation to degeneration: the lessons of clinical trials.
AB  - About two-third of patients with multiple sclerosis (MS) accumulate severe
      disabilities before the age of 50. Disability depends mostly on axonal loss even
      if persistent conduction block also may be a contributing factor. Axonal loss is
      predominant in the early phase of the disease and is strictly related to the
      inflammatory activity. In this phase the axonal damage is mostly, if not
      exclusively, determined by axonal transection inside the lesions, so that
      reduction of the lesion rate results in a proportional effect of the irreversible
      tissue damage. With disease evolution, the redundancy of the central nervous
      system (CNS) starts to be insufficient to compensate the axonal loss resulting
      from reactivation (or persistence at a low degree) of inflammatory activity
      inside the lesions, secondary axonal degeneration of axons damaged by previous
      attacks and (possibly) by a primitive axonal degeneration. In this phase of the
      disease, most of the irreversible damage does not depend on new lesions; as a
      consequence, the reduction of disease activity produces only marginal efforts on
      nervous tissue degeneration. Clinical trials demonstrate that the positive effect
      of immunomodulatory and anti-inflammatory therapies is maximal in patients with
      clinically isolated syndromes and it starts to decrease in relapsing-remitting
      phases and is almost lost in secondary-progressive phases. From the practical
      point of view, early treatment is mandatory.

PMID- 14652794
TI  - Multiple sclerosis: rationale for early treatment.
AB  - MS often presents as acute unilateral optic neuritis (ON). While it is clear that
      many patients with ON suffer from a generalized disease of the central nervous
      system that will go on to clinically definite MS (CDMS), it is also clear that
      others do not. As patients become increasingly wellinformed and with the
      development of effective pharmacotherapy for MS, the distinction between those
      patients with ON who have MS and those who do not has become ever more important.
      Recent randomized clinical trials in patients with ON or other clinically
      isolated syndromes (CIS) suggestive of MS and evidence of prior subclinical
      demyelination on magnetic resonance imaging of the brain found that treatment
      with recombinant interferon-beta-1a is beneficial in reducing the development of
      CDMS. Ophthalmologists and other non-neurologists should refer patients with
      acute ON or other CIS suggestive of MS to a neurologist for MS-directed
      investigations.

PMID- 14652795
TI  - Beta-2 microglobulin and neopterin as markers of disease activity in multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a predominately T helper 1-mediated autoimmune disease
      of the central nervous system. Magnetic resonance imaging (MRI) is the most
      useful tool for monitoring disease activity and progression. However, MRI is an
      expensive and time-consuming test. Therefore, the ability to measure biological
      markers in body fluids correlating with MRI disease activity is of great
      importance. Beta-2 microglobulin (beta2-MG) and neopterin have been found to
      correlate with disease activity in several autoimmune disorders and are used as
      pharmacodynamic markers of interferon beta treatment in MS. During the natural
      course of MS, beta2-MG is stable over time, and thus it is unlikely that
      monitoring its plasma levels will be a useful marker of disease changes. More
      controversial results have been found for neopterin evaluations in MS. Urinary
      excretion of neopterin is higher during a clinical relapse but blood levels of
      this molecule do not correlate with clinical and MRI measurements.

PMID- 14652797
TI  - Screening and brief alcohol interventions in trauma centers.
AB  - A third of all trauma beds are occupied by patients injured while under the
      influence of alcohol, yet trauma centres currently treat the injury and ignore
      the underlying alcohol problem. The incorporation of brief interventions to
      motivate patients to reduce alcohol intake has been associated with a reduction
      of their drinking and a resultant decrease in health care costs. While trauma
      centres are ideally situated for alcohol screening, interventions, and referral,
      the efficacy of such a program should be confirmed and the strategies for its
      optimal implementation in the routine practise of care should be further
      evaluated.

PMID- 14652796
TI  - New FKRP mutations causing congenital muscular dystrophy associated with mental
      retardation and central nervous system abnormalities. Identification of a founder
      mutation in Tunisian families.
AB  - The congenital muscular dystrophies (CMD) constitute a clinically and genetically
      heterogeneous group of autosomal recessive myopathies. Patients show congenital
      hypotonia, muscle weakness, and dystrophic changes on muscle biopsy. Mutations in
      four genes (FKT1, POMGnT1, POMT1, FKRP) encoding putative glycosyltransferases
      have been identified in a subset of patients characterized by a deficient
      glycosylation of alpha-dystroglycan on muscle biopsy. FKRP mutations account for
      a broad spectrum of patients with muscular dystrophy, from a severe congenital
      form with or without mental retardation (MDC1C) to a much milder limb-girdle
      muscular dystrophy (LGMD2I). We identified two novel homozygous missense FKRP
      mutations, one, A455D, in six unrelated Tunisian patients and the other, V405L,
      in an Algerian boy. The patients, between the ages of 3 and 12 years, presented
      with a severe form of MDC1C with calf hypertrophy and high serum creatine kinase
      levels. None had ever walked. Two had cardiac dysfunction and one strabismus.
      They all had mental retardation, microcephaly, cerebellar cysts, and hypoplasia
      of the vermis. White matter abnormalities were found in five, mostly when cranial
      magnetic resonance imaging was performed at a young age. These abnormalities were
      shown to regress in one patient, as has been observed in patients with Fukuyama
      CMD. Identification of a new microsatellite close to the FKRP gene allowed us to
      confirm the founder origin of the Tunisian mutation. These results strongly
      suggest that particular FKRP mutations in the homozygous state induce structural
      and clinical neurological lesions in addition to muscular dystrophy. They also
      relate MDC1C to other CMD with abnormal protein glycosylation and disordered
      brain function.

PMID- 14652798
TI  - Control of immune responses by savenger liver endothelial cells.
AB  - The liver appears to be an organ favoring the induction of immune tolerance
      rather than immunity. Among the hepatic cell populations possibly involved in
      regulation of immune responses, liver sinusoidal endothelial cells (LSEC) are
      well suited to fulfill this role. LSEC are resident cells lining the hepatic
      sinusoidal wall and therefore are in intimate contact with leukocytes passing
      through the liver. They are equipped with numerous scavenger receptors rendering
      antigen-uptake in these cells extremely efficient. Antigen processing and MHC
      restricted presentation of exogenous antigens for CD4 as well as CD8 T cells
      occurs equally with high efficiency. Importantly, CD4 and CD8 T cells that
      engaged in cognate interaction with LSEC have a tolerant phenotype. Thus LSEC
      contribute an important immune function to the liver: control of the immune
      response against circulating soluble antigens.

PMID- 14652799
TI  - Increased detection rates of Barrett's oesophagus without rise in incidence of
      oesophageal adenocarcinoma.
AB  - QUESTIONS UNDER STUDY/PRINCIPLES: The incidence of oesophageal adenocarcinoma has
      quadrupled in the last 20 years. Barrett's oesophagus carries a 30- to 125-fold
      increased risk of developing adenocarcinoma. The purpose of this study was to
      evaluate the incidence and surveillance of Barrett's oesophagus, dysplasia and
      adenocarcinoma in Eastern Switzerland. METHODS: Histological reports of 3659
      patients (5190 oesophageal biopsies) from the St. Gallen Institute of Pathology
      were searched for evidence of Barrett's oesophagus (period 1989-1999). After
      retrospective classification according to findings on endoscopy and histology,
      the data were analysed with regard to surveillance intervals and incidence rates
      of Barrett's oesophagus, dysplasia and adenocarcinoma. RESULTS: 742 patients with
      Barrett's oesophagus and 100 with oesophageal adenocarcinoma were identified and
      followed up for a mean 1.6 (1-11) years. The average incidence of Barrett's
      oesophagus rose from 8.5/10(5)/yr (CI-95%: 7.4-9.7) in the first to 15.5/10(5)/yr
      (CI-95% 14.0-17.0) in the second 5-year period. The incidence of adenocarcinoma
      in our study population was 0.5% (1/97 patient years). In 207 patients (25%) with
      follow-up of >1 year, 9% progressed to low grade and 1% to high grade dysplasia,
      and 5% to adenocarcinoma. Adequacy of surveillance in BE patients rose from 54%
      to 87% over the study period. CONCLUSIONS: There is an increasing incidence of
      Barrett's oesophagus, which is not accompanied by an increase in oesophageal
      adenocarcinoma, in Eastern Switzerland. Surveillance of Barrett's oesophagus is
      often inadequate in spite of relevant findings such as dysplasia.

PMID- 14652800
TI  - Elevation of B-type natriuretic peptide levels in acute respiratory distress
      syndrome.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) has been proven to be a biochemical
      marker of severity of congestive heart failure. We are aware of only few papers
      reporting the association of BNP elevation and pulmonary hypertension (primary,
      thromboembolic, or as a consequence of chronic obstructive pulmonary disease).
      Less is known about BNP in patients with acute respiratory distress syndrome
      (ARDS). CASE DESCRIPTION AND RESULTS: We present the case of a previously healthy
      27-year-old man with parapneumonic ARDS and an extraordinarily increased BNP
      level. The ventricular systolic ejection fraction assessed echocardiographically
      was normal with no evidence of left ventricular diastolic dysfunction. However, a
      peak BNP level of >1300 pg/mL (normal <100 pg/mL) was recorded. Repeated BNP
      values were obtained on nine separate days over a period of 3 weeks of mechanical
      ventilation. With the respiratory improvement following the inhalation of nitric
      oxide BNP levels decreased to 113 pg/mL. The possible pathophysiological
      mechanisms of BNP release are discussed. CONCLUSION: There is evidence for BNP
      elevation in the absence left ventricular dysfunction. This case is an example of
      impressively high BNP levels associated with ARDS, probably attributable to right
      ventricular overload due to increased pulmonary vascular resistance.

PMID- 14652801
TI  - Chernobyl--opening the pages to scientific authors from Eastern Europe.

PMID- 14652802
TI  - Monitoring of radiation-induced germline mutation in humans.
AB  - Estimating the genetic hazards of radiation and other mutagens in humans depends
      on extrapolation from experimental systems. Recent data have shown that
      minisatellite loci provide a useful and sensitive experimental approach for
      monitoring radiation-induced mutation in humans. This review describes the
      progress made in validating this approach and presents the results of recent
      publications on the analysis of minisatellite mutation rates in the irradiated
      families.

PMID- 14652803
TI  - Adverse cardiac events in ICU patients with presumptive antidepressant overdose.
AB  - BACKGROUND: Antidepressants account for most poison-related admissions to
      intensive care units. In selected patients with confirmed cyclic antidepressant
      intoxication a QRS interval <0.1 s in the ECG limb leads during the first six
      hours excludes adverse cardiac events. However, the incidence of cardiac events
      and the value of ECG criteria have never been assessed prospectively on patients
      with presumed antidepressant overdose. AIM: To assess ingested drugs, adverse
      cardiac events, and ECG findings in ICU patients with a presumptive diagnosis of
      antidepressant overdose. METHODS: 103 consecutive patients with a presumptive
      diagnosis of antidepressant overdose were enrolled and prospectively followed.
      Outcome criteria were arrhythmias, mortality, and duration of the ICU stay.
      RESULTS: Mixed intoxication was identified in 66 (64%) patients. Tricyclic
      antidepressants were found in 88 (85%), and serotonin-reuptake inhibitors in 25
      (24%) patients. Mean APACHE II score was 9.5 (SD +/- 6.0). Arrhythmias affected
      15 (15%) and cardiopulmonary resuscitation was performed on 4 (4%) patients.
      Three patients (3%) died in the ICU. Median duration of the ICU stay was 1 day
      (12 hours to 6 days). Adverse cardiac events affected patients with normal and
      prolonged QRS interval at study entry. CONCLUSIONS: Mixed intoxication is present
      in most ICU patients with suspected antidepressant overdose. There is a
      considerable risk for adverse cardiac events, even in the presence of normal ECG
      recordings within the first six hours after hospital admission.

PMID- 14652804
TI  - Experiences in diagnosis and treatment of hip dislocation and dysplasia in
      populations screened by the ultrasound method of Graf.
AB  - Ultrasound investigation of the hip according to Graf is performed, whenever
      possible, as a routine screening test for hip dysplasia and dislocation in
      neonates. However, in spite of screening, hip dysplasia and/or dislocation is
      identified in a number of children after the third month of life only. The
      present study presents an analysis of reasons and causes. Between August 1999 and
      July 2001 children aged between six months and five years were documented, in
      whom the diagnosis of hip dysplasia or dislocation was made, despite normal
      ultrasound findings at primary investigation and who required non operative or
      operative treatment by a specialist surgeon working in Switzerland in paediatric
      orthopaedics. The study included 26 children (17 girls / 9 boys). Hip dysplasia
      and/or dislocation was diagnosed between the age of 6 days and 41 months. Twelve
      children had to be excluded from the sample (n = 26), four were infants who had
      basic neurological disorders or multiple anomalies and there were eight children
      from abroad whose original documentation could not be obtained. Analysis of the
      remaining 14 children showed that 43% were misdiagnosed (n = 6) and a treatment
      error occurred in 36% (n = 5) of cases. One child presented with a teratogenic
      hip dislocation. In two other infants with normal primary ultrasound findings,
      hip dysplasia was identified radiographically once the child started to walk.
      Delayed diagnosis can be the result of technical errors or misinterpretation. The
      six patients meeting the criteria of misinterpretation can be expressed as a rate
      of 0.04% of all births. However, even if the disorder is correctly diagnosed, its
      identification and treatment may be inadequate or fail to produce the desired
      results. This was the case for five of the children, that is, for a rate of 0.03%
      of births.

PMID- 14652805
TI  - Chronic Cs-137 incorporation in children's organs.
AB  - In Belarus's Gomel region, which was heavily contaminated by fallout from the
      Chernobyl disaster, we have studied the evolution of the Cs-137 load in the
      organisms of the rural population, in particular children, since 1990. Children
      have a higher average burden of Cs-137 compared with that of adults living in the
      same community. We measured the Cs-137 levels in organs examined at autopsy. The
      highest accumulation of Cs-137 was found in the endocrine glands, in particular
      the thyroid, the adrenals and the pancreas. High levels were also found in the
      heart, the thymus and the spleen.

PMID- 14652806
TI  - Can we agree to disagree?

PMID- 14652807
TI  - Curriculum content and evaluation of resident competency in anatomic pathology: a
      proposal.
AB  - In response to new requirements laid down by the Accreditation Council for
      Graduate Medical Education (ACGME), the Association of Directors of Anatomic and
      Surgical Pathology (ADASP) has developed a detailed curriculum, as well as
      guidelines for assessing competence, for resident training in anatomic pathology,
      focused principally on the core competencies in patient care and medical
      knowledge. The proposed curriculum described herein is offered as a template for
      potential use (with or without any necessary local modifications) by pathology
      training programs. Other areas of competency (eg, practice-based learning,
      interpersonal/communication skills, professionalism, and systems-based practice)
      are covered elsewhere on the Program Directors in Pathology and ACGME websites.

PMID- 14652808
TI  - Curricula for pathology training: an editorial comment.

PMID- 14652809
TI  - Interobserver and intraobserver reproducibility in the histopathology of
      follicular thyroid carcinoma.
AB  - We evaluated the interobserver and intraobserver reproducibility in the
      histopathology of follicular thyroid carcinoma (FTC). Forty-one anonymous FTC
      pathology slides were independently reviewed by 5 pathologists, and 31 of them
      were also evaluated twice by the same pathologist. A final consensus diagnosis
      (FCD) was made at the end of the study. Interobserver and intraobserver agreement
      was determined as the kappa statistic for qualitative data and intraclass
      correlation coefficient for quantitative data. The agreement between the 5
      observers' initial diagnosis and the FCD was 0.69, 0.41, 0.35, 0.28 and 0.11,
      respectively, strongly suggesting a leadership phenomenon. The FCD classified 30
      cases as malignant, including 24 cases diagnosed as FTC. There was unanimous
      agreement about 13 of the 24 FTCs. Diagnostic reproducibility was found to be
      acceptable for the nonminimally invasive FTC. Diagnostic discrepancies occurred
      in 57% of the seven cases classified as minimally invasive FTC by the FCD. FCD
      excluded malignancy in 11 cases including 6 atypical adenomas. Interobserver and
      intraobserver agreement for FTC diagnosis was 0.23 (standard error [SE], 0.04)
      and 0.68, respectively. Interobserver and intraobserver agreement for the
      presence of vascular invasion was 0.20 (SE, 0.04) and 0.51, respectively,
      contrasting with a moderate to substantial level of agreement when considering
      the number of vascular invasion. Interobserver and intraobserver agreement for
      nucleus optical clearing were slight and moderate, respectively. The importance
      of the study is the confirmation that diagnostic reproducibility of minimally
      invasive FTC is low and that this has clinical implications, and also
      implications for the design of studies into the treatment and outcome of FTC.

PMID- 14652810
TI  - Sinonasal adenocarcinoma: evidence for histogenetic divergence of the enteric and
      nonenteric phenotypes.
AB  - Adenocarcinomas of nonsalivary origin represent approximately 10% to 20% of all
      sinonasal malignancies and are characterized by varying histopathologic features
      and uncertain histogenesis. To better understand the histogenesis and phenotypic
      heterogeneity of these tumors, we performed immunohistochemical analyses for
      cytokeratin (CK) 7 and CK20 on 12 primary sinonasal adenocarcinomas (SNACs)
      representing the histopathologic spectrum of these tumors, adjacent normal
      mucosa, and 2 metastatic adenocarcinomas from colonic primaries. The demographic
      and clinicopathologic characteristics of our cohort were similar to those in
      previously published series. Our results indicate that histologically normal
      respiratory-type epithelium and submucosal seromucous glands show restricted
      reactivity to CK7. Epithelial metaplasia of surface epithelium associated with
      enteric SNACs was accompanied by a conversion from CK7 positivity to CK20
      positivity. All primary enteric-type carcinomas and the 2 colonic metastases were
      reactive to CK20, but all nonenteric-type tumors were negative for CK20 (P=0.003)
      and positive for CK7. In some of the enteric types, coexpression of CK7 and CK20
      was noted. We conclude that (1) nonenteric-type (seromucinous) adenocarcinoma may
      originate directly from surface respiratory-type epithelium or from seromucous
      glands, (2) metaplastic transformation of surface respiratory to enteric-type
      epithelium precedes the development of enteric adenocarcinoma, and (3) coordinate
      analyses of CK7 and CK20 reactivity may aid the differential diagnosis of
      adenocarcinoma in the sinonasal tract.

PMID- 14652811
TI  - Primary esophageal small cell carcinoma with concomitant invasive squamous cell
      carcinoma or carcinoma in situ.
AB  - Esophageal small cell carcinoma (SmCC) is a rarer, more highly aggressive, and
      more rapidly growing neoplasm than esophageal squamous cell carcinoma (SqCC).
      SmCC and SqCC also differ in terms of chemotherapy of choice, response to
      therapy, and prognosis. Accordingly, it is important to differentiate the 2
      carcinomas. We studied the histology and immunohistochemical profiles of 6 cases
      of esophageal SmCC to elucidate the correct diagnosis of this tumor. We performed
      immunohistochemical analysis antibodies against cytokeratins (CKAE1/AE3,
      CKCAM5.2, CK34betaE12, CK7, CK8, CK10/13, and CK19), epithelial membrane antigen
      (EMA), neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE),
      chromogranin-A, S-100 protein, carcinoembryonic antigen (CEA), E-cadherin,
      thyroid transcription factor-1 (TTF-1), and p53. In 3 of the 6 SmCCs,
      heterogeneous components of in situ or invasive SqCC were observed. SqCC was
      found in the mucosa adjacent to the main SmCC, and the boundary between SmCC and
      SqCC was distinct, with no transitional features. Staining for NCAM, NSE, and
      chromogranin-A was positive in SmCCs, but negative in SqCCs. Both SmCCs and SqCCs
      were positive for CKAE1/AE3, CKCAM5.2, CK8, and EMA, but only SqCCs were positive
      for CK34betaE12 and CK19. Moreover, SmCCs containing SqCC components were
      positive for CEA and E-cadherin, whereas SmCCs without SqCC were negative. Our
      study suggests that NCAM and NSE are useful markers in diagnosing esophageal
      SmCC, and CK34betaE12 and CK19 are useful for differentiating SqCC components
      from SmCC.

PMID- 14652812
TI  - Threshold for diagnosing prostate cancer over time.
AB  - Paralleling the detection of earlier prostate cancer over the last several years,
      there have been numerous efforts to educate practicing pathologists on the
      diagnosis of limited prostate cancer on needle biopsy via journal articles, Web
      sites, books, and educational courses. The current study was undertaken to assess
      whether the threshold for the diagnosis of prostate cancer on needle biopsy has
      lowered over time. One thousand twelve prostate needle biopsy cases obtained in
      consultation by 1 of the authors because of diagnostic concerns over a period of
      12 weeks (November 15, 2001 to February 15, 2002) were reviewed. Cases referred
      by either the patient or clinicians were excluded. The final diagnoses in this
      series were compared with a previously published series of needle biopsy cases of
      the prostate seen in consultation by the same author in 1993-1994. The percentage
      of cancer in the 2001-2002 series was 55.1%, compared with 69.6% for the 1993
      1994 series. The mean and median numbers of malignant glands in the 2001-2002
      series (mean, 21.9; median, 14; range, 2 to 296) were significantly smaller than
      in the 1993-1994 series (mean, 31.0; median, 20; range, 2 to 300; P<0.00001). The
      incidence of atypical glands that were suspicious for but not diagnostic of
      carcinoma was 23.9% in the 2001-2002 series and was 10.7% in the 1993-1994
      series. The mean and median numbers of atypical glands in the 2001-2002 series
      were 9.4 and 6, respectively (range, 1 to 70); these parameters were not
      available for the previous series. The percentage of high-grade prostatic
      intraepithelial neoplasia diagnoses was similar in the 2001-2002 and 1993-1994
      series (5.1% and 4.6%, respectively), as was the overall frequency of benign
      cases (15.8% and 15.1%, respectively). The percentage of cases that were
      accompanied by immunohistochemical stains for 34betaE12 in the 2001-2002 series
      was 44.4%, which was much more than the 2.5% seen in the 1993-1994 series; if
      anything, this should have resulted in a lower atypical rate in the current
      series. In more recent years, cases sent for consultation have more limited
      cancer, with a correspondingly higher percentage of cases that are diagnosed as
      atypical, yet not diagnostic of cancer. The number of atypical glands in the
      recent series was very limited, such that a change over time in the threshold for
      diagnosing cancer by the consultant is an unlikely explanation. It appears that
      pathologists are becoming more skilled at diagnosing limited prostate cancer and
      are referring predominantly cases with fewer cancer glands and more difficult
      atypical cases with few glands.

PMID- 14652813
TI  - Nuclear translocation of survivin in hepatocellular carcinoma: a key to cancer
      cell growth?
AB  - Survivin is a recently described anti-apoptosis protein and regulator of cell
      division. Its expression and localization in hepatocellular carcinoma (HCC) and
      in normal liver tissue has not been fully elucidated. We examined the expression
      of survivin, Fas, proliferating cell nuclear antigen (PCNA), and apoptosis in 47
      specimens of hepatocellular carcinoma (HCC) and surrounding nonmalignant hepatic
      tissues. To further determine the relationship between survivin expression and
      cell proliferation and apoptosis, we performed double immunostaining for survivin
      and PCNA TUNEL staining in the same HCC specimens. Positive immunostaining for
      survivin was present in 35 of 47 (74%) HCCs. Twenty-two of 35 survivin-positive
      HCCs (63%) showed punctate nuclear staining in HCC cells, and the remaining 13
      showed predominant cytoplasmic staining. In contrast, nonmalignant hepatocytes
      showed only cytoplasmic staining. HCC cells had significantly higher PCNA
      labeling and apoptotic indices compared with the case of nonmalignant hepatic
      tissue (P<0.001). Furthermore, nucleus-positive HCC specimens for survivin showed
      the highest PCNA labeling index. The nuclear localization of survivin in HCC
      cells correlated with tumor cell de-differentiation with the exception of the
      HepG2 cell line. Survivin expression was inversely associated with apoptosis and
      was strongly associated with Fas expression (P=0.01). All 4 HCC cell lines
      examined showed survivin expression and punctate nuclear localization. Our
      results indicate that survivin is localized to the cytoplasm in quiescent
      nonmalignant liver cells to suppress apoptosis and translocates into the nucleus
      in HCC cells. In conclusion, translocation of survivin from the cytoplasm to the
      nucleus may constitute an important regulatory mechanism for cell proliferation
      and differentiation in HCC.

PMID- 14652814
TI  - Liver transplantation for primary sclerosing cholangitis: a long-term
      clinicopathologic study.
AB  - The course and outcome of patients after liver transplantation (LT) for primary
      sclerosing cholangitis (PSC) are still debated. Our purpose is to define
      retrospectively, the post-LT clinicopathologic findings seen in 51 PSC patients
      with a follow-up of 2 to 14 years. Of the total 51 patients, 16 with native liver
      hilar xanthogranulomatous cholangiopathy (XGC) had median graft and patient
      survival of 573 and 835 days, respectively compared with 2489 and 2794 days,
      respectively, in 35 patients without XGC. Perioperative complications resulted in
      9 early deaths (day 0 to 52). Of the remaining 42 patients, 6 had recurrent PSC
      (R-PSC) with typical histologic and cholangiographic findings, 12 had autoimmune
      liver disease-not otherwise specified with histology of autoimmune
      hepatitis/overlap syndrome, 3 had chronic rejection, 4 had ischemic
      cholangiopathy, and 17 had no recurrence. The presence of inflammatory bowel
      disease, total ischemia time of > or =11 hours, recipient-donor ABO and HLA Class
      I and II matches, and the type of immunosuppression did not affect the post-LT
      outcome. Recipient-donor gender mismatch was more common in R-PSC than in the
      nonrecurrent group (P=0.045). Post-LT malignancies were significantly more common
      in the nonrecurrent cases compared with all others combined (P=0.031) and caused
      deaths in 4. The majority of deaths (11/13) in other groups were due to sepsis
      complicating graft dysfunction. In conclusion, allograft autoimmune liver disease
      was seen in 18 (43%) of 42 long-term post-LT PSC patients, with progression in 5
      of 18 patients. Features of PSC were seen in 6 (33%) of 18. Native liver XGC
      negatively impacted post-LT graft and patient survival. Increased incidence of
      malignancies in the nonrecurrent group may reflect overimmunosuppression in those
      patients.

PMID- 14652815
TI  - Neoplasms involving the central nervous system in the older old.
AB  - Geriatric cancer patients present special challenges for clinicians. Few large
      series have been published in the last 20 years on the types of neoplasms that
      involve the central nervous system (CNS) in older individuals. To review types of
      neoplasms involving the central CNS that are currently being encountered by
      pathologists and neurosurgeons, we identified from our databases for the years
      1992-2002, inclusive, patients 75 years or older who had symptomatic lesions
      requiring neurosurgical interventions. Retrospective characterization of tumors
      by immunohistochemistry, in situ hybridization, and fluorescence in situ
      hybridization was performed whenever possible and relevant to tumor type.
      Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients
      were diagnosed as having neoplasms, with clot evacuation or infections being the
      most frequent non-neoplastic conditions necessitating surgery. Tumor types
      included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12),
      lymphomas or other hematological malignancies (8), anaplastic gliomas (5),
      metastases (6), head and neck malignancies with direct intracranial extension
      (3), and other miscellaneous tumor types (4). Compared with older literature
      series, we encountered a larger number of elderly patients with CNS lymphomas and
      fewer who came to surgery for CNS metastatic disease. In the "older old",
      glioblastomas are the most frequent symptomatic tumors necessitating surgical
      intervention. Glioblastomas in this aged cohort display the signature features of
      the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1
      labeling index=25.1%), and either amplification of epidermal growth factor
      receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of
      assessable cases).

PMID- 14652816
TI  - Expression of PC-cell-derived growth factor in benign and malignant human breast
      epithelium.
AB  - PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth
      factor that is overexpressed in human breast cancer cell lines. We have examined
      immunohistochemical PCDGF expression in 206 paraffin-embedded human breast
      lesions and investigated its association with clinicopathological variables.
      PCDGF staining was observed in breast carcinoma, whereas it was almost always
      negative in benign breast epithelium. PCDGF expression was more common in
      invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma
      (53% positive). PCDGF staining was almost never observed in lobular carcinoma in
      situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this
      expression correlated strongly with nuclear grade. Similar correlation was
      observed between PCDGF expression and histologic grade of invasive ductal
      carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive
      carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive
      tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a
      staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative
      tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression
      and of ER and PR status. Our study provides the first evidence of high incidence
      of PCDGF expression in human breast cancer in which it correlates with
      clinicopathological variables such as tumor grade, proliferation index, and p53
      expression. These characteristics, as well as the virtual absence of expression
      in benign breast tissue, suggest an important role of PCDGF in breast cancer
      pathogenesis and make it a potential novel target for the treatment of breast
      cancer.

PMID- 14652817
TI  - Expression of calretinin and other mesothelioma-related markers in thymic
      carcinoma and thymoma.
AB  - Thymic carcinoma and thymoma are primary neoplasms of the anterior mediastinum
      that can involve the lung and pleura in advanced stages or, in rare instances,
      occur as primary pleural tumors. Thus these tumors may be encountered in thoracic
      and pleural biopsy specimens. Recognizing the immunohistochemical patterns of
      calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma
      may be helpful in avoiding confusion with malignant mesothelioma and pulmonary
      carcinoma, both of which are major differential diagnoses in this location.
      Accordingly, in the present study we examined the expression of calretinin,
      mesothelin, cytokeratin (CK) 5/6, thrombomodulin, HBME-1, Wilms' tumor-1 (WT-1),
      Ber-EP4, MOC-31, BG-8, B72.3, carcinoembryonic antigen (CEA), CD15, thyroid
      transcription factor-1 (TTF-1), p63, and CD5 in 22 thymic carcinomas and 35
      thymomas, and compared the results with those of malignant mesothelioma and
      pulmonary adenocarcinoma. Around 1/3 of thymic carcinomas were positive for
      calretinin and/or mesothelin. Both thymic carcinomas and thymomas were frequently
      positive for CK 5/6. Immunoreactivity for HBME-1 was seen in 4 thymic carcinomas
      and 10 thymomas. Except for 1 thymic carcinoma being positive for WT-1, all other
      thymic carcinomas and thymomas were negative for WT-1 and thrombomodulin. None of
      the thymic carcinomas and thymomas expressed TTF-1. More than 70% of the thymic
      carcinomas were positive for Ber-EP4, BG-8, and CD15. The positive rates of MOC
      31, B72.3, and CEA in thymic carcinomas were in the middle between those in
      mesothelioma and pulmonary adenocarcinoma. All thymic epithelial tumors revealed
      nuclear immunoreactivity for p63. Nine thymic carcinomas (41%) expressed CD5. We
      found that a panel of positive p63, negative thrombomodulin, WT-1, and TTF-1 is
      most discriminatory for thymic epithelial tumors. Other mesothelial (calretinin
      and mesothelin) and epithelial (Ber-EP4, BG-8, and CD15) markers are less
      contributory in discerning thymic epithelial tumors due to their overlapping
      expression with malignant mesothelioma and pulmonary adenocarcinoma. Given the
      complexity of the staining patterns among the different entities, proper
      immunohistochemical stainings should be selected and interpreted with caution,
      and correlated with clinicopathologic findings in the differential diagnoses of
      thoracic biopsy specimens.

PMID- 14652818
TI  - Heterogeneous versus homogeneous genetic nature of multiple foci of in situ
      carcinoma of the breast.
AB  - The vast majority of in situ breast cancers represent focal lesions all derived
      from a single clone and requiring local treatment alone. We focused our attention
      on rare cases of multicentric in situ carcinomas affecting different quadrants,
      which required mastectomy. Defining the origin from single- or multiple-cell
      clones of separate independent neoplastic foci in the breast may be of
      pathogenetic interest and of importance in deciding the type of therapy to be
      administered. We employed a molecular assay based on loss of heterozygosity (LOH)
      and human androgen receptor assay (HUMARA) analysis of microdissected samples
      from 19 mastectomies. Two or more tissue samples were obtained from 7 patients
      with multicentric lobular in situ carcinoma (LCIS), either classical or large
      cell variety; and 12 patients with multicentric ductal in situ carcinomas (DCIS),
      either low-grade (7 cases) or high-grade (5 cases) variety. Separate foci of high
      grade (comedonic) DCIS were found to be monoclonal in nature. On the contrary,
      definite evidence favoring the origin from different cell clones of separate
      carcinomatous foci within the same breast was obtained in 2 cases of low-grade
      DCIS and in 6 cases of LCIS. A genetic imbalance might be the factor favoring the
      development of multifocal heterogeneous foci of in situ breast cancer. Such a
      small subgroup of in situ cancers affecting diffusely the entire breast and
      originating from independent foci presents both clinical and pathogenetic
      interest.

PMID- 14652819
TI  - Expression of Epstein-Barr virus in thyroid carcinoma correlates with tumor
      progression.
AB  - There have been few studies regarding cancer progression from differentiated
      thyroid carcinoma to the undifferentiated one. To examine the possible
      involvement of Epstein-Barr virus (EBV) in this progression, 10 papillary
      carcinomas and 11 undifferentiated carcinomas were subjected to mRNA in situ
      hybridization, indirect immunofluorescence staining, polymerase chain reaction
      (PCR), and reverse-transcriptase PCR. mRNA in situ hybridization using a BamHIW
      probe revealed signals in all of the examined samples, although the signal
      strength was weaker in the papillary carcinomas than in the undifferentiated
      carcinomas. EBV nuclear antigen-2 (EBNA2) in situ hybridization produced almost
      the same results; however, the signals were detected less frequently in the
      papillary carcinomas. Indirect immunofluorescence using anti-EBNA2, anti-latent
      membrane protein-1 (LMP1), and anti-BZLF1 antibodies also showed positive results
      with high frequency and with more prominent fluorescence in undifferentiated
      carcinomas than in papillary carcinomas. An examination of thyroid carcinoma cell
      lines also confirmed these findings. EBV infected all of the thyroid carcinomas
      irrespective of the degree of pathological differentiation. The expression of
      EBV, especially of EBNA2 and LMP1 (both of which are oncogene products of EBV),
      was stronger in the undifferentiated carcinomas than in the papillary carcinomas.
      These results suggest that increased expression of EBV may be involved in the
      progression of thyroid papillary carcinoma to undifferentiated carcinoma.

PMID- 14652820
TI  - Clonality analysis of different histological components in combined small cell
      and non-small cell carcinoma of the lung.
AB  - Combined small cell and non-small cell carcinoma is relatively rare in the lung.
      Examination of the clonal relationship of different components in this type of
      tumor may give a clue to the rarity. We retrieved 6 such tumors; all 6 had small
      cell carcinoma and adenocarcinoma components, and 3 had an additional squamous
      cell carcinoma component. We examined the point mutations in the p53 gene and
      allelic loss (ie, the loss of heterozygosity [LOH] pattern) of chromosome 3p in
      each component. p53 mutations were detected in the small cell carcinoma component
      of 5 tumors and in the non-small cell carcinoma components of 2 tumors. In 1
      case, the squamous cell carcinoma component had a p53 mutation locus identical to
      that in the small cell carcinoma component, but in the other case, the
      adenocarcinoma component had a different mutation than that in the small cell
      carcinoma component. Chromosome 3p LOH loci in the squamous cell carcinoma
      component were present in the small cell carcinoma component in all 3 cases, but
      some LOH loci were not identical in the small cell carcinoma and adenocarcinoma
      components in 3 cases. These results suggest that the small cell and squamous
      cell carcinoma components of combined small cell lung carcinomas have an intimate
      clonal relationship. On the other hand, the adenocarcinoma component often may be
      derived from a separate clone or, more likely, undergo a progressive process
      separate from the squamous cell-small cell carcinoma beginning in a very early
      stage, that is, before the appearance of p53 and chromosome 3p abnormalities.
      This tumorigenesis process may explain the relative rarity of combined small cell
      and non-small cell carcinoma, which occurs primarily in the peripheral lung, an
      infrequent site of squamous cell carcinoma.

PMID- 14652821
TI  - Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis:
      intracellular consensus bacterial 16S rRNA is associated with the
      gastrointestinal but not the cutaneous manifestations of Crohn's disease.
AB  - The classic pathology of skin disease discontinuous from the inflamed
      gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes
      pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic
      Crohn's disease. The purpose of this study was two-fold: First, we explored the
      full spectrum of cutaneous lesions associated with Crohn's disease, and second,
      we sought to explore a potential molecular basis of the skin lesions in patients
      with CD. In this regard, we analyzed skin and GI tract biopsies from affected
      patients for the consensus bacterial SrRNA to determine whether direct bacterial
      infection was associated with either condition. Formalin-fixed, paraffin-embedded
      sections were studied and correlated to clinical presentation and histories from
      33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT
      in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract
      material included biopsies from 3 patients who had skin lesions and from 7
      patients in whom there were no known skin manifestations. There were 8 cases of
      neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases
      of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile
      neutrophilic folliculitis, 5 cases of panniculitis, 4 cases of vasculitis, 2
      cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and 1
      case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8
      of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were
      from patients who also developed skin lesions at some point in their clinical
      course; in contrast, none of the skin biopsies had detectable bacterial RNA. The
      dermatopathological manifestations of CD discontiguous from the involved GI tract
      mucosa have in common a vascular injury syndrome, typically with a prominent
      extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition,
      this study, the first to document in situ intracellular consensus bacterial SrRNA
      in the GI tract in CD, suggests that hematogenous dissemination of viable
      microbes is not associated with the cutaneous manifestations of this disease.
      Bacteria do, however, appear to play a role in bowel lesions of patients with CD.

PMID- 14652822
TI  - Computerized diagnostic decision support system for the classification of
      preinvasive cervical squamous lesions.
AB  - Previous studies have revealed considerable interobserver and intraobserver
      variation in the histological classification of preinvasive cervical squamous
      lesions. The aim of the present study was to develop a decision support system
      (DSS) for the histological interpretation of these lesions. Knowledge and
      uncertainty were represented in the form of a Bayesian belief network that
      permitted the storage of diagnostic knowledge and, for a given case, the
      collection of evidence in a cumulative manner that provided a final probability
      for the possible diagnostic outcomes. The network comprised 8 diagnostic
      histological features (evidence nodes) that were each independently linked to the
      diagnosis (decision node) by a conditional probability matrix. Diagnostic
      outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia
      (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was
      recorded that represented the full spectrum of change for that feature. The
      system was designed to be interactive in that the histopathologist was prompted
      to enter evidence into the network via a specifically designed graphical user
      interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions
      were used to derive the relative likelihoods for the alternative feature
      outcomes, the likelihood vector was entered into the network, and the updated
      diagnostic belief was computed for the diagnostic outcomes and displayed. A
      cumulative probability graph was generated throughout the diagnostic process and
      presented on screen. The network was tested on 50 cervical colposcopic biopsy
      specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and
      CIN III. These had been preselected by a consultant gynecological pathologist.
      Using conventional morphological assessment, the cases were classified on 2
      separate occasions by 2 consultant and 2 junior pathologists. The cases were also
      then classified using the DSS on 2 occasions by the 4 pathologists and by 2
      medical students with no experience in cervical histology. Interobserver and
      intraobserver agreement using morphology and using the DSS was calculated with
      kappa statistics. Intraobserver reproducibility using conventional unaided
      diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver
      agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall
      reproducibility between individuals. Using the DSS, however, did not enhance the
      diagnostic performance of junior pathologists when comparing their DSS-based
      diagnosis against an experienced consultant. However, the generation of a
      cumulative probability graph also allowed a comparison of individual performance,
      how individual features were assessed in the same case, and how this contributed
      to diagnostic disagreement between individuals. Diagnostic features such as
      nuclear pleomorphism were shown to be particularly problematic and poorly
      reproducible. DSSs such as this therefore not only have a role to play in
      enhancing decision making but also in the study of diagnostic protocol,
      education, self-assessment, and quality control.

PMID- 14652823
TI  - Activating Gs alpha mutation at the Arg201 codon in liposclerosing myxofibrous
      tumor.
AB  - Liposclerosing myxofibrous tumor (LSMFT) is a benign fibro-osseous lesion that is
      characterized by mixture of histologic elements including lipoma, fibroxanthoma,
      myxoma, ischemic ossification, and fibrous dysplasia (FD)-like features. These
      tissue components are seen in the original reports of FD; however, the
      relationship between LSMFT and FD is not clear. Point mutation of the alpha
      subunit of G protein (Gs alpha), which increases cyclic adenosine monophosphate
      formation, has been recognized as the cause of McCune-Albright syndrome as well
      as polyostotic and monostotic FD of bone. Gs alpha mutation at the Arg201 codon
      in 2 patients of LSMFT was demonstrated in the present study. Although direct
      sequencing analysis using the fresh-frozen materials could not detect the
      mutation, the polymerase chain reaction fragmentation length polymorphism (PCR
      RFLP) disclosed the missense point mutation Gs alpha at the Arg201 codon in 2
      cases involving LSMFT. This result strongly suggests that a subset of LSMFT is a
      variant form of FD.

PMID- 14652824
TI  - Rosai-Dorfman disease of the pleura: a rare extranodal presentation.
AB  - We present a case of Rosai-Dorfman disease (sinus histiocytosis with massive
      lymphadenopathy) manifesting primarily as a pleural disease without involvement
      of the lung parenchyma. The patient is an 81-year-old man who presented with
      increasing shortness of breath. Radiographic studies revealed a large loculated
      left-sided pleural effusion and parietal pleural thickening. Video-assisted
      thoracoscopic biopsy of the pleura showed the characteristic S100-positive
      histiocytes exhibiting emperipolesis. In this rare case of pleural Rosai-Dorfman
      disease, the extensive involvement of the pleural lymphatics by the
      characteristic histiocytes appears to have been responsible for the pleural
      effusion.

PMID- 14652825
TI  - T(14;18)(q32;q21) involving MALT1 and IGH genes in an extranodal diffuse large B
      cell lymphoma.
AB  - Two translocations involving the MALT1 gene have been described in extranodal
      marginal zone B-cell lymphomas of MALT type. A t(11;18)(q21;q21) involving API2
      and MALT1 occurs in a subset of MALT lymphomas but with only rare exception is
      absent in diffuse large B-cell lymphomas (DLBCL), even at MALT sites. More
      recently, a t(14;18)(q32;q21) involving IGH and MALT1 has been described in
      nongastric extranodal MALT lymphomas. This translocation is indistinguishable
      from the IGH-BCL2 translocation by using classical cytogenetics. We report the
      IGH-MALT1 translocation in a cutaneous DLBCL as shown by classical cytogenetics
      and molecular cytogenetic analysis. This is the first report of an IGH-MALT1
      translocation in DLBCL. These findings indicate that MALT1 translocations are not
      restricted to indolent-appearing lymphomas, provide further evidence that API2
      MALT1 and IGH-MALT1 translocations exhibit biologic differences, have
      implications regarding the pathogenesis of some extranodal DLBCL, and emphasize
      that a t(14;18)(q32;q21) cannot be assumed to reflect a BCL2 translocation.

PMID- 14652826
TI  - Combined folliculotropic/syringotropic cutaneous T-cell lymphoma without
      epidermal involvement: report of 2 cases and pathogenic implications.
AB  - Exclusive involvement of skin appendages in cutaneous T-cell lymphoma (CTCL) is
      rare, poses significant problems in diagnosis, and may provide insight into
      mechanisms of T-cell epitheliotropism. We report 2 cases of combined adnexal
      (folliculotropic/syringotropic) CTCL in which lesions developed only in
      chronically sun-damaged skin. Although the epidermal layer in both cases was
      devoid histologically of significant epidermotropism, immunohistochemistry and
      polymerase chain reaction analyses of deeper samples that included involved
      adnexae confirmed aberrant antigen expression (dominant CD4 populations with
      apparent loss of CD7 and/or CD5) and T cell clonality, respectively. It is
      diagnostically important to recognize adnexal CTCL as a disorder that may be
      clinically and histologically protean. Additionally, its occurrence in sun
      damaged skin in some patients may provide insight into mechanisms of selective
      epitheliotropism by malignant T cells.

PMID- 14652830
TI  - Upper extremity ischemia and hemodialysis vascular access.
AB  - Digital ischemia in dialysis patients due to arteriovenous fistulas (AVF) is a
      rare condition, occurring in 4% of patients. The etiology is different from lower
      limb ischemia. Blood shunting through the AVF may cause stealing of blood and
      hypoperfusion in distal tissues, leading to pain, discolorisation and ulcers.
      High-flow AVFs have greater risk on ischemia than normal flow AVFs, however
      combined with peripheral arteriosclerotic disease the latter may also leads to
      ischemia. A non-invasive and angiographic diagnosis is of importance to determine
      treatment options. Augmentation of arterial inflow by interventional techniques
      and/or AVF bloodflow-reducing surgical procedures may eliminate pain and heal
      ulcers. The best results are obtained by bypassing the arteriovenous anastomotic
      site and interruption of steal phenomenon by ligation of the artery distal to the
      AV anastomosis.

PMID- 14652831
TI  - The role of statins in vascular disease.
AB  - BACKGROUND: Recent publications have highlighted the benefits of statins in non
      cardiac occlusive disease but also the failure of vascular surgeons to recognise
      and treat the risk factors for atherosclerosis, in particular
      hypercholesterolaemia. The aim of this review is to clarify the current
      experimental and clinical evidence for the use of statins in vascular disease.
      METHODS: Literature compiled from an extensive search of Medline and the Cochrane
      database has been used for the basis of this review. RESULTS: Experimental and
      clinical evidence consistently reports that statins improve endothelial
      dysfunction, are anti-inflammatory, anti-proliferative, anti-thrombogenic and
      anti-proteolytic. These effects are known to inhibit atherogenesis and improve
      plaque stability. Independent groups support the use of statins in the prevention
      of both primary and secondary cardiac events. The National Stroke association
      recommends their use to reduce strokes following myocardial infarction and the
      Heart Protection Study reports benefits in patients with non-cardiac occlusive
      disease. CONCLUSIONS: There is substantial evidence advocating the use of statins
      in patients with clinically significant vascular disease. In the future this may
      evolve to include those patients at risk from neointimal hyperplasia, aneurysmal
      disease and ischaemia reperfusion injury.

PMID- 14652832
TI  - Does supervised exercise offer adjuvant benefit over exercise advice alone for
      the treatment of intermittent claudication? A randomised trial.
AB  - OBJECTIVE: Exercise advice is the main treatment for symptom relief in the UK for
      patients with mild to moderate Intermittent Claudication (IC). Would a weekly
      exercise and motivation class for 6 months offer adjuvant benefit over written
      and verbal exercise advice alone? PATIENTS AND METHODS: Fifty-nine patients
      attending a regional vascular centre for whom IC was the main factor affecting
      mobility were randomised to either exercise advice alone (n=30) or exercise
      advice with a once a week 45 min supervised exercise/motivation class (n=29). The
      mean age was 68 years. Baseline and 6-month assessment included a Quality of Life
      Questionnaire--the Short-Form-36, the Charing Cross Symptom Specific Claudication
      Questionnaire (CCCQ) and treadmill walking distance (3.5 km/h 12%). RESULTS: At 6
      month follow-up the supervised exercise group had improved their treadmill
      walking by 129% compared to 69% in the advice alone group (p=0.001). This
      significant improvement was maintained at the subsequent 9 and 12-month follow-up
      assessments. By the 9-month stage the advice only group CCCQ score had improved
      16% from baseline, while the supervised exercise group had a significantly better
      43% improvement in base line score (p<0.05). Self reported frequency of walks was
      higher in the exercise class group being significant for improvement in CCCQ
      score. CONCLUSION: A weekly, supervised exercise and motivation class for a 6
      month period provides a significant improvement in patients' symptoms, quality of
      life, and distance walked compared with advice alone and this improvement
      continues after attendance at class has ceased.

PMID- 14652833
TI  - Predictors of treatment outcome in intermittent claudication.
AB  - OBJECTIVE: To derive formulae to predict the likely 12-month health-related
      quality of life outcome following different treatments for intermittent
      claudication (IC). DESIGN: A prospective, randomized, controlled study.
      MATERIALS: One hundred and seventy-one unselected patients with stable IC were
      sequentially randomized to invasive therapy, supervised physical training or
      observation. Hierarchical analysis was used to identify significant predictors of
      outcome. RESULTS: The strongest outcome predictors were baseline values of the
      respective outcome variables in all groups. No more than two significant
      secondary predictors were identified for each outcome variable and no outcome
      variable was a predictor of any other outcome variable. Resulting prediction
      equations achieved between 61 and 90% concordance with improvement (75%
      considered adequate), with best prediction for invasive therapy and poorest for
      observation. Suggested cutpoints for the various endpoints in the three groups
      had sensitivities ranging between 65 and 100% and false positive rates between 5
      and 50%. CONCLUSIONS: The derived equations adequately predicted improvement on
      the various outcome variables in invasive therapy and supervised physical
      training, and may serve as aids in selecting patients likely to benefit most from
      a particular treatment strategy. The uniqueness of the outcome variables
      underscores the importance of implementing a comprehensive set of endpoints
      relevant to the impacts of the condition.

PMID- 14652834
TI  - Influence of the textile structure on the degradation of explanted aortic
      endoprostheses.
AB  - OBJECTIVES: To investigate mechanisms of textile failure in explanted human
      aortic endoprostheses. MATERIALS AND METHODS: Endoprostheses (n31) underwent
      optical and scanning electron microscopy, filament dynamometry, and saturation
      index measurement. RESULTS: The macroscopic lesions observed in the Stentor and
      Vanguard devices were holes at the extremities of the stents and slipping of the
      warp yarns at the level of sutures or of the longitudinal seams. The macroscopic
      lesions observed in AneurX endoprostheses were holes, slipping of the warp yarns
      and ruptures of the ligatures. The macroscopic lesions observed in the two Talent
      endoprostheses were sections of fibers at the level of the suture holes and few
      areas lesions of wear, with sometimes holes at the contact of the stent
      extremities. Stentor, Vanguard and AneurX all demonstrated low saturation indexes
      of the fabric (44-59%) with an important anisotropy. Whereas the Talent endograft
      demonstrated a high index of saturation (124-131%) with a low anisotropy. We did
      not demonstrate significant polymer degradation in any of the endoprostheses.
      CONCLUSIONS: It is essential to take into account the saturation index to
      optimally choose a woven textile for the construction of an endoprosthesis since
      this property of the textile may contribute to explain the macroscopic lesions
      observed. We did not observe significant polymer degradation by filament
      dynamometry but further studies are needed to confirm these data.

PMID- 14652835
TI  - A cautionary case: the SynerGraft vascular prosthesis.
AB  - To date no prosthetic vascular prosthesis performs as well as autologous conduits
      for small diameter arterial reconstruction. We report the outcome of our first
      case using a new vascular prosthesis marketed by Cryolife, the SynerGraft. This
      Xenograft prostheses is claimed to eliminate the problems of the previous
      generation of gluteraldehyde treated grafts. Two 50 cm SynnerGrafts were
      anastomosed end to end and used as a femoral-posterior tibial bypass graft in a
      68-year-old man who presented with an acutely ischaemic left leg. Our patient
      represented at 8 weeks with aneurysmal degeneration along the course of the
      graft. We urge caution in the use of these grafts until convincing data in humans
      is presented.

PMID- 14652836
TI  - Endotension is influenced by wall compliance in a latex aneurysm model.
AB  - OBJECTIVES: Even though endovascular aneurysm repair (EVAR) creates a closed
      chamber except for patent branches, the intra-sac pressure is never zero. This
      study was designed to investigate whether, and to what extent, aneurysm wall
      compliance influences intra-sac pressure. DESIGN: In vitro experimental study.
      METHODS: Aneurysm models with six and 12 latex layers were produced, resulting in
      elastic and stiff circumferential compliance (3.5 +/- 0.5 and 0.9 +/- 0.3%/100
      mmHg, respectively). The models with an 18 mm internal neck and maximum aneurysm
      diameter of 60 mm were inserted into an in vitro circulation system. The systemic
      mean pressure (SPmean) was varied from 50 to 120 mmHg. After the aneurysm was
      excluded with a knitted polyethylene graft, aneurysm sac mean pressure (ASPmean)
      and aneurysm sac pulse pressure (ASPpulse) were measured. Data are presented as
      mean +/- SD. Statistics were performed using repeated measurements of variance;
      p<0.05 was considered significant. RESULTS: In the model EVAR created a closed
      chamber without endoleak, but with an aneurysm sac pressure related to wall
      compliance. In the elastic aneurysm model with six latex coats the aneurysm sac
      mean pressure (ASPmean) and the aneurysm sac pulse pressure (ASPpulse) at all
      systemic pressures were significantly lower than they were in the stiffer model
      with 12 latex coats (p<0.05). At a SPmean of 90 mmHg, the ASPmean was 21.0 +/-
      0.9 mmHg (six latex coats) and 26.0 +/- 0.2 mmHg (12 latex coats) (p<0.05), the
      ASPpulse was 5.7 +/- 0.2 mmHg (six latex coats) and 8.8 +/- 0.3 mmHg (12 latex
      coats) (p<0.05). CONCLUSIONS: This in vitro model demonstrated that the aneurysm
      sac mean pressure (ASPmean) and the aneurysm sac pulse pressure (ASPpulse) were
      significantly influenced by the compliance of the aneurysm wall. These data
      highlight the need for further studies regarding endotension.

PMID- 14652837
TI  - A UK multi-centre experience with a second-generation endovascular stent-graft:
      results from the Zenith Users Group.
AB  - BACKGROUND: Endovascular aneurysm repair has been criticised for high rates of
      technical failure and secondary intervention. Second generation stent-grafts have
      been developed in an attempt to reduce these problems. The results of a UK multi
      centre experience with a second generation device (Zenith) are presented.
      METHODS: Data were collected retrospectively from five experienced UK vascular
      centres in patients undergoing endovascular aneurysm repair with the Zenith stent
      graft. RESULTS: A total of 269 patients underwent attempted aneurysm repair with
      the Zenith device. Median aneurysm diameter was 65 (interquartile range 52-78)
      mm. There were no conversions to open repair. Peri-operative mortality was 4.1%
      (11/269). On the initial post-operative scan, 94.1% of aneurysms were
      successfully excluded. During a median follow-up of 363 (interquartile range 154
      720) days there were 19 secondary interventions and two aneurysm ruptures.
      CONCLUSIONS: Second generation endovascular stent-graft designs such as the
      Zenith are associated with low rates of intra-operative technical complications.
      Few secondary interventions have been necessary during follow-up; however,
      surveillance is essential to ensure they continue to perform.

PMID- 14652838
TI  - The value of abdominal examination in the diagnosis of abdominal aortic aneurysm.
AB  - BACKGROUND: There is considerable variability in the reported value of clinical
      examination in the diagnosis of abdominal aortic aneurysms (AAA). This study aims
      to assess accuracy of abdominal examination by a doctor, a nurse and the patient
      in the diagnosis of AAA and whether this accuracy is related to the size of the
      aneurysm and/or the BMI of the patient. METHODS: 164 patients, 138 men and 26
      women, median age 71 years, consented to participate in this prospective, single
      blind, controlled study. Thirty-nine patients attending for carotid duplex were
      used as controls. Abdominal examination was performed by a doctor and a nurse.
      Patients then performed self-examination. RESULTS: Examination by a doctor, a
      nurse and the patient were similar in accuracy in diagnosing/excluding AAA which
      was directly related to AAA size and patient BMI. The Negative Predicted Value of
      abdominal examination exceeds 0.9 with AAA diameters > or =4 cm and the Positive
      Predictive Value exceeds 0.8 with AAA diameters > or =5 cm. CONCLUSIONS:
      Abdominal examination by a doctor, a nurse and the patient is of value in the
      exclusion and diagnosis of significant AAA. It should be promoted and may
      represent a useful adjunct to population screening with ultrasound.

PMID- 14652839
TI  - Does the sequence of clamp application during open abdominal aortic aneurysm
      surgery influence distal embolisation?
AB  - BACKGROUND: Embolisation of atherosclerotic debris during abdominal aortic
      aneurysm (AAA) repair is responsible for significant peri-operative morbidity.
      Reports have suggested that preferential clamping of the distal vessel(s) before
      the proximal aorta may decrease the number of emboli passing distally and hence
      reduce complications. METHODS: Forty patients undergoing AAA repair were
      randomised to have either first clamping of the proximal aorta or the iliac
      vessels. Emboli passing through the Superficial Femoral Arteries were detected
      with a Transcranial Doppler ultrasound system. RESULTS: There was no difference
      between the two groups in the number of emboli detected (p=0.49) and no
      significant correlation between number of emboli and dissection time (r=0.0008).
      However, there was a significantly higher number of emboli in the patient sub
      group that were current smokers (p=0.034). CONCLUSIONS: There appears to be no
      difference in the numbers of emboli detected when the first vascular clamp is
      applied to the proximal aorta or iliacs.

PMID- 14652840
TI  - The post-operative mortality of ruptured abdominal aortic aneurysm repair.
AB  - INTRODUCTION: Late peri-operative death after ruptured abdominal aortic aneurysm
      (RAAA) repair is usually due to multiple-organ failure. The aim of this study was
      to identify any factors that are associated with mortality in this group of
      patients. METHODS: A retrospective case-note review of a single decade's
      operative experience of RAAA repair in a single centre. Only those patients with
      confirmed rupture at laparotomy were included. Sixty-three pre- intra- and post
      operative variables were recorded where possible for each patient who survived
      surgery and the initial 24-hours post-operatively. Multi-variate analysis was
      performed using stepwise logistic regression. The P-POSSUM, RAAA-POSSUM, RAAA
      POSSUM (physiology only), V-POSSUM, and V-POSSUM (physiology only) models were
      all compared to determine how each performed in these patients. RESULTS: Two
      hundred and twenty-three cases of confirmed RAAA were identified, of whom 139
      survived the operation and initial 24-hours post-operatively. In-hospital
      mortality in this group of patients was 32.4%. Variables significantly associated
      with mortality after multi-variate analysis, were low intra-operative systolic
      blood pressure, the presence of a consultant anaesthetist at the initial
      operation and the development of cardiac, renal or gastro-intestinal
      complications. All POSSUM models except the V-POSSUM and P-POSSUM (physiology
      only) models demonstrated no significant lack of fit in this dataset. DISCUSSION:
      Factors associated with delayed peri-operative death after RAAA are not the same
      as those previously found to be associated with overall peri-operative mortality
      after RAAA repair.

PMID- 14652841
TI  - Abdominal aortic aneurysm and its correlation to plasma homocysteine, and
      vitamins.
AB  - BACKGROUND: Hyperhomocysteinemia is a recognised independent risk factor in the
      genesis of atherosclerotic diseases. However, very little is known about the
      relationship between homocysteine and abdominal aortic aneurysm (AAA). Vitamins,
      namely B12 and folic acid have been implicated in the regulation of plasma
      homocysteine levels. However, there has been no prospective study that has
      analysed the relationship of AAA and plasma homocysteine in light of serum
      vitamin levels. AIMS: To study the relationship between plasma homocysteine,
      serum B12 and folic acid levels, and AAA. METHOD: Case control study including 38
      AAA patients and 36 controls. Fasting homocysteine, B12 and folic acid were
      determined in serum separated within 1 h of blood collection using a fluorescence
      polarisation immunoassay technique (FPIA). RESULTS: Twenty-six (68%) of the AAA
      patients had elevated levels of homocysteine compared to 2 (6%) in the case
      control group. The mean homocysteine level in the AAA group was 19.4 micromol/L
      (SE +/- 1.1) (95% CI 17.17-21.65) and in the control group was 10.9 micromol/L
      (SE +/- 1) (95% CI 9.95-11.88) (p<0.001). Mean vitamin B12 levels in the AAA and
      the controls was 332.11 pg/L (SE +/- 16.44) and 414.33 pg/L (SE +/- 19.72),
      respectively (p<0.004). Mean folic acid in the AAA was 8.02 (SE +/- 0.71) and the
      control was 9.8 etagm/L (SE +/- 0.69), (ns). CONCLUSION: This study confirms
      significantly higher levels of plasma homocysteine in AAA patients but lower
      levels of B12. Use of supplemental vitamins that should lower plasma homocysteine
      may modify vascular disease progression. Clinical trials in this direction are
      warranted.

PMID- 14652842
TI  - Renal artery clamping and left renal vein division during abdominal aortic
      aneurysm repair.
AB  - OBJECTIVES: To determine whether renal artery clamping and division of the left
      renal vein affects renal function in the patients who undergo repair of
      infrarenal abdominal aortic aneurysm (AAA). METHODS: Between 1992 and 2000, 267
      patients had open surgery for infrarenal AAA. Of these, 22 (8%) required
      temporary bilateral (15) or unilateral (7) renal artery clamping. 8 also had the
      left renal vein divided, three of which were re-anastomosed. RESULTS: Renal
      artery clamping and/or renal vein divisions did not affect the incidence of
      complications and long term renal failure. CONCLUSIONS: Clamping of the renal
      arteries and/or renal vein division during AAA surgery does not in itself
      compromise short or long term renal function.

PMID- 14652843
TI  - Reconstruction of the vena cava with the peritoneum: the effect of temporary
      distal arteriovenous fistula on patency (an experimental study).
AB  - OBJECTIVE: To determine the effect of increasing inferior vena cava blood flow by
      means of distal arteriovenous fistula on the patency of a peritoneal tube graft.
      MATERIALS AND METHODS: In 16 mongrel dogs, a 3-4 cm long circular defect was
      created at the infrarenal inferior vena cava. The defect was interposed with
      peritoneal tube graft. A temporary distal femoro-femoral arteriovenous fistula
      was also constructed in 8 dogs just after the caval interposition. Graft patency
      was evaluated by Doppler ultrasonography and angiography. Histological evaluation
      was also performed. RESULTS: Seven dogs in each group survived. All control
      grafts occluded within the first week, compared to no occlusions in fistula group
      (Fisher's exact test, p<0.005). However one 'fistula' dog with a still patent
      graft was sacrificed on the 18th day due to ultrasonographically occluded
      arteriovenous fistula. CONCLUSION: In dogs, the peritoneum may be used as graft
      material for reconstruction of the inferior vena cava, provided a distal
      arteriovenous fistula is constructed.

PMID- 14652844
TI  - Relationship of plasma vascular endothelial growth factor to CEAP clinical stage
      and symptoms in patients with chronic venous disease.
AB  - OBJECTIVE: Skin damage caused by chronic venous disease (CVD) is associated with
      severe microangiopathic changes in the skin. The aim was to determine whether
      patients in various CEAP clinical stages of CVD have elevated plasma levels of
      VEGF compared to controls and whether this correlates with the symptoms. METHODS:
      One hundred and eight patients with CVD attending the vascular clinic were
      included and assigned to the appropriate CEAP clinical stage. Thirty healthy
      control subjects were also included. Patients and controls were studied after
      resting supine for 10 min. Blood samples were taken from a dorsal foot vein.
      Assay of VEGF was performed with an enzyme-linked immunosorbent assay.
      Volunteers' symptoms were recorded using a visual analogue scale (VAS) for
      heaviness, cramps, paraesthesiae and swelling. RESULTS: Plasma levels of VEGF
      were: control (n30) median VEGF 56 pg/ml (inter-quartile range IQR 38-85), CEAP
      C2 (varicose veins) 86 (39-133), C5 (healed ulcer) 88 (67-135). Median
      difference: control vs. C5 33 (95% confidence interval (CI) 8-61). Median
      differences were calculated using the Wilcoxon method. VEGF level in patients
      with VAS swelling score=0:54 pg/ml (IQR 31-104). VEGF level in patients with VAS
      swelling score >0:85 pg/ml (IQR 40-147). Difference between medians: 20 ng/ml,
      95% CI for the median difference: (5-44). No differences were observed for
      symptoms of heaviness, cramps or paraesthesiae. CONCLUSION: There was a trend
      towards raised VEGF in all stages of CVD, but this only reached statistical
      significance in those with healed ulceration. The symptom of swelling was
      associated with raised VEGF levels; however, the symptoms of heaviness, cramps,
      and paraesthesiae were not associated with raised VEGF levels.

PMID- 14652845
TI  - Multi-layer compression: comparison of four different four-layer bandage systems
      applied to the leg.
AB  - OBJECTIVE: To compare performance of four commercial four-layer bandage systems
      when applied to the leg. METHODS: Four experienced bandagers applied each system:
      [Profore Regular (Smith and Nephew); Ultra-Four (Robinson); System 4 (Seton) and
      K Four (Parema)] to the same leg. Bandages were applied as single layers and as
      completed systems using standard techniques. For each application, 18 pressure
      measurements were taken using the Borgnis Medical Stocking Tester (MST) at three
      measuring points (ankle, gaiter and mid-calf) on medial and lateral aspects in
      three postures: (horizontal, standing and sitting). RESULTS: In all 2304
      observations were made, 576 for each bandager, 576 for each bandaging system, 768
      for each measuring point, 1152 for each aspect and 768 for each posture. The
      increase in pressure produced by each additional layer was 65-75% of the pressure
      of the same bandage when used as a single layer. There were significant
      differences in the final pressures achieved by the bandagers (means: 45-54 mmHg,
      p<0.001) and between bandage systems (means: System 4: 46 mmHg, Profore: 47 mmHg,
      K Four: 52 mmHg, Ultra-Four: 54 mmHg; p=0.005). The relationships between the
      final pressures achieved at each of the three measuring points, the three
      postures and the two aspects were not consistent among the bandage systems
      (p<0.01). CONCLUSIONS: When a bandage is applied as part of a multi-layered
      system it exerts approximately 70% of the pressure exerted when applied alone,
      thus challenging the commonly-held assumption that the final pressure achieved by
      a multi-layer bandaging system is the sum of the pressures exerted by each
      individual layer. Each of the four bandaging systems exerted different final
      pressures and gradients and different changes with posture change. These
      differences have important implications, which could influence the selection (or
      avoidance) of a particular bandage system according to a patient's condition and
      circumstances.

PMID- 14652846
TI  - Comparison of antero-posterior and transverse aortic diameters: implications for
      routine aneurysm surveillance.

PMID- 14652849
TI  - The source of cells for allografting.
AB  - Peripheral blood is used almost exclusively as the source of hematopoietic cells
      for autografting, but the best source of cells for allografting is the subject of
      considerable discussion and debate. Randomized studies comparing unstimulated
      bone marrow with G-CSF-mobilized peripheral blood in the sibling allogeneic
      setting have indicated a trend to more chronic graft-versus-host disease in
      peripheral blood recipients. However, whether the use of G-CSF-mobilized
      peripheral blood cells leads to more acute graft-versus-host disease is
      uncertain. Adults undergoing sibling allografting appear to benefit in terms of
      improved disease-free survival or improved overall survival with the use of G-CSF
      mobilized peripheral blood. It is not clear, however, whether these benefits also
      extend to children or those undergoing matched unrelated transplantation.

PMID- 14652850
TI  - Adoptive immunotherapy to increase the level of donor hematopoietic chimerism
      after nonmyeloablative marrow transplantation for severe canine hereditary
      hemolytic anemia.
AB  - Severe hemolytic anemia in Basenji dogs secondary to pyruvate kinase deficiency
      can be corrected by allogeneic hematopoietic cell transplantation (HCT) from
      littermates with normal hematopoiesis after conventional myeloablative or
      nonmyeloablative conditioning regimens. If the levels of donor chimerism were low
      (<20%) after nonmyeloablative HCT, there was only partial correction of the
      hemolytic anemia. We next addressed whether allogeneic cell therapy after
      nonmyeloablative HCT would convert mixed to full hematopoietic chimerism, achieve
      sustained remission from hemolysis, and prevent progression of marrow fibrosis
      and liver cirrhosis. Three pyruvate kinase-deficient dogs were given HCT from
      their respective dog leukocyte antigen-identical littermates after
      nonmyeloablative conditioning with 200 cGy of total body irradiation.
      Postgrafting immunosuppression consisted of mycophenolate mofetil and
      cyclosporine. All 3 dogs engrafted and had mixed hematopoietic chimerism with
      donor levels ranging from 12% to 55% in bone marrow. In 2 of the 3 dogs, there
      were decreases in the levels of donor chimerism so that at 25 weeks after
      nonmyeloablative HCT, hemolysis recurred that was associated with increased
      reticulocyte counts. All 3 dogs then had 2 serial infusions of donor lymphocytes
      (DLI) from their respective donors at least 20 weeks apart to convert from mixed
      to full donor chimerism. Both dogs with recurrence of hemolytic anemia after
      nonmyeloablative HCT achieved higher levels of donor chimerism, with donor
      contributions ranging from 47% to 62% in the bone marrow and 50% to 69% and 16%
      to 25% in the granulocyte and mononuclear cell fractions of the peripheral blood,
      respectively, and with remission of the hemolytic anemia. One dog responded after
      the first DLI, and 5 weeks after the second DLI, the other dog converted to full
      donor chimerism. At last follow-up, all these dogs showed clinical improvement,
      as determined by increasing hematocrits and normal reticulocyte counts. Analysis
      of the marrow 3 years after HCT showed normal cellularity, a normal myeloid
      erythroid ratio, and no or minimal marrow fibrosis. Liver biopsies demonstrated
      normal histologies with no or minimal fibrosis. We conclude that DLI after
      nonmyeloablative HCT can increase the levels of donor cells contributing to
      hematopoiesis in recipients, inducing remissions of the hemolytic process and
      preventing complications associated with iron overload.

PMID- 14652851
TI  - Renal pathology at autopsy in patients who died after hematopoietic stem cell
      transplantation.
AB  - Acute and chronic renal dysfunction are common after hematopoietic stem cell
      transplantation (HSCT). Although the pathology of chronic HSCT nephropathy is
      well described, the histologic changes that accompany acute renal dysfunction
      after HSCT are less well known because renal biopsies are rarely undertaken in
      the peritransplantation period. Archival renal tissue from consecutive HSCT
      recipients who died and underwent autopsy at a single center during an 8-year
      period was studied. Abnormalities of renal pathology were described, and
      associations of histologic abnormalities with clinical events were systemically
      studied. Abnormalities of renal histology were common among the 26 patients in
      this study. The 3 most common histologic abnormalities were glomerular sclerosis
      (19/26; 73%), tubular epithelial atypia (19/26; 73%), and tubular calcification
      (18/26; 69%). Tubulitis (16/24; 67%) and interstitial fibrosis (16/26; 62%) were
      also frequently observed. Clinical veno-occlusive disease was not associated with
      histologic evidence of thrombotic microangiopathy in the kidney at autopsy. Also,
      clinical graft-versus-host disease was not associated with renal tubulitis.
      Unexpectedly, the proportion of patients with tubular atrophy (54%) or
      interstitial fibrosis (62%) was high, considering the young age of the patients
      at transplantation and their normal pretransplantation creatinine clearance. Well
      recognized histologic abnormalities are common in the kidneys of patients who die
      after HSCT. Although we did not demonstrate associations of these histologic
      changes with clinical variables before death, larger studies with prospectively
      collected renal tissue are warranted.

PMID- 14652852
TI  - Hematopoietic cell transplantation from related and unrelated donors after
      minimal conditioning as a curative treatment modality for severe paroxysmal
      nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a
      somatic mutation of the X-linked phosphatidylinositol glycan class A gene.
      Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning
      is the only curative treatment; however, it is associated with high treatment
      related mortality. Here, we report on allogeneic HCT for PNH after minimal
      conditioning. Seven adult patients with high-risk PNH underwent peripheral blood
      HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and
      unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m(2)/d on days 
      4 to -2 and 2 Gy of total body irradiation on day 0. After HCT, patients were
      given immunosuppressive therapy with oral cyclosporine starting on day -3 and
      mycophenolate mofetil starting on day 0. All 7 patients attained durable
      engraftment. After 28 days, a median of 77% (range, 53%-96%) T-cell donor
      chimerism was found in bone marrow and peripheral blood. T-cell chimerism
      increased to 91% (range, 76%-100%) on day +180 and to 100% in all surviving
      patients after 12 months. All 7 patients attained complete remissions of their
      disease. Four patients are alive 13 to 38 months after HCT. Three patients died
      of treatment-related mortality, 1 because of complications after acute
      pancreatitis and multiorgan failure, 1 because of infection related to chronic
      graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy
      for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors
      after minimal conditioning is a new and potentially curative option for patients
      with advanced PNH.

PMID- 14652853
TI  - Hemorrhagic cystitis after allogeneic bone marrow transplantation in children:
      clinical characteristics and outcome.
AB  - Hemorrhagic cystitis (HC) is a well-documented adverse event experienced by
      patients undergoing hematopoietic stem cell transplantation. When severe, HC
      causes significant morbidity, leads to renal complications, prolongs
      hospitalization, increases health-care costs, and occasionally contributes to
      death. We retrospectively studied the medical records of 245 children undergoing
      an initial allogeneic bone marrow transplantation for malignant disease at St.
      Jude Children's Research Hospital between 1992 and 1999 to describe the clinical
      course of HC in all patients and to identify the risk factors for HC in this
      cohort. Conditioning regimens included cyclophosphamide, cytarabine, and total
      body irradiation. Grafts from unrelated or mismatched related donors were
      depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All
      patients received cyclosporine as prophylaxis for graft-versus-host disease.
      Recipients of grafts from matched siblings also received pentoxifylline or short
      course methotrexate. Severe HC developed in 27 patients (11.0%). The median
      duration of HC was 73 days (range, 5-619 days); 12 patients had ongoing HC at the
      time of death. In univariate analyses, patients were at increased risk of severe
      HC if they were male (P =.021) or had received T cell-depleted grafts (P =.017),
      grafts from unrelated donors (P =.021), a lower total nucleated cell dose (P
      =.032), or antithymocyte globulin (P =.0446). Multiple regression analysis
      revealed male sex (beta =.97; P =.027) and unrelated donor graft recipients (beta
      =.83; P =.039) to be significant factors.

PMID- 14652854
TI  - Survival after second hematopoietic stem cell transplantation for recurrent
      pediatric acute myeloid leukemia.
AB  - Recurrent acute myeloid leukemia (AML) after hematopoietic stem cell
      transplantation (HSCT) predicts a dismal prognosis. We sought to determine
      whether a second HSCT would result in long-term disease-free survival with
      acceptable toxicity. We evaluated the outcome of a second HSCT with a preparative
      regimen of cyclophosphamide and total body irradiation in pediatric patients with
      AML who relapsed after an initial HSCT with a busulfan and cyclophosphamide
      preparative regimen. Twenty-five patients aged 1.1 to 17.2 years (median, 4.1
      years) with AML received a second HSCT for recurrent disease. All patients were
      conditioned with busulfan and cyclophosphamide for the first HSCT and with
      cyclophosphamide and total body irradiation for the second HSCT. Donor sources
      for the first HSCT were autologous (n = 11) or allogeneic (n = 14), whereas all
      donors for the second HSCT were allogeneic (12 matched related, 9 mismatched
      related, and 4 unrelated). Engraftment after the second HSCT occurred in all
      patients at median of 19.0 days (range, 11-32 days). The cumulative incidence of
      grade II to IV graft-versus-host disease was 76% after the second HSCT. Three
      patients died from regimen-related toxicity before day 100, 9 relapsed at a
      median of 5.4 months (range, 1.8-34.0 months), and 12 survived a median of 9.1
      years (range, 7.0-14.4 years) after the second HSCT. The Kaplan-Meier estimates
      of survival at 100 days, 1 year, and 10 years were 88%, 56%, and 48%,
      respectively. The disease-free survival rate at 10 years was 44%. Multivariate
      Cox regression analysis suggested that patients who received a second HSCT in
      relapse had a relative risk of relapse of 7.8 (P =.02) compared with patients who
      underwent transplantation in remission. In addition, patients who received their
      second HSCT </=6 months after the first transplantation were at increased risk of
      relapse (P =.03). These data suggest that second HSCT after a failed initial
      transplantation results in long-term disease-free survival in one half of
      children with relapsed AML. Because a higher tumor burden at the time of second
      HSCT was associated with a higher risk of subsequent relapse, patients might
      benefit from reinduction therapy before the second HSCT.

PMID- 14652855
TI  - Hydroxychloroquine for the prevention of acute graft-versus-host disease after
      unrelated donor transplantation.
AB  - Hydroxychloroquine (HCQ) is an immunosuppressive agent that interferes with
      antigen presentation and with activity against graft-versus-host disease (GVHD).
      In a phase II trial assessing the GVHD prophylactic effects of HCQ, 51
      consecutive unrelated donor transplant recipients received HCQ in addition to
      cyclosporin A, methylprednisolone, and methotrexate. HCQ was initiated on
      pretransplantation day -21 at 800 mg/d and continued until day +100 after
      transplantation. HCQ was extremely well tolerated and was not associated with
      side effects. Pharmacokinetic analyses demonstrated large inter- and intrapatient
      variability. The addition of HCQ did not affect posttransplantation immune
      recovery. Grade II to IV acute GVHD was observed in 56% of patients, and grade
      III and IV GVHD was observed in 17%. Day +100 mortality was 22%. When compared
      with a matched cohort of patients reported to the International Bone Marrow
      Transplant Registry, patients receiving HCQ had comparable cumulative incidences
      of grade II to IV acute GVHD. However, lower incidences of grades III and IV GVHD
      and better GVHD-free survival were observed in HCQ-treated patients (P =.01). We
      conclude that prophylactic HCQ is well tolerated and associated with a low
      incidence of severe acute GVHD. An ongoing placebo-controlled randomized trial
      will further determine what role HCQ plays in preventing GVHD after allografting.

PMID- 14652861
TI  - Simple procedures for blinded sample size adjustment that do not affect the type
      I error rate.
AB  - For normally distributed data, determination of the appropriate sample size
      requires a knowledge of the variance. Because of the uncertainty in the planning
      phase, two-stage procedures are attractive where the variance is reestimated from
      a subsample and the sample size is adjusted if necessary. From a regulatory
      viewpoint, preserving blindness and maintaining the ability to calculate or
      control the type I error rate are essential. Recently, a number of proposals have
      been made for sample size adjustment procedures in the t-test situation.
      Unfortunately, none of these methods satisfy both these requirements. We show
      through analytical computations that the type I error rate of the t-test is not
      affected if simple blind variance estimators are used for sample size
      recalculation. Furthermore, the results for the expected power of the procedures
      demonstrate that the methods are effective in ensuring the desired power even
      under initial misspecification of the variance. A method is discussed that can be
      applied in a more general setting and that assumes analysis with a permutation
      test. This procedure maintains the significance level for any design situation
      and arbitrary blind sample size recalculation strategy.

PMID- 14652862
TI  - A note on non-parametric ANCOVA for covariate adjustment in randomized clinical
      trials.
AB  - Koch et al. recently (1998) proposed two covariate-adjusted approaches for the
      comparison of continuous, ordinal and binary responses in a randomized clinical
      trial (Statist. Med. 1998; 17: 1863-1892). The first is a randomization approach
      while the second assumes that the study is a sample of a population. Here, we
      study the second approach and consider the simplest cases of two treatments with
      a continuous response and with a binary response. Koch's second approach will be
      compared with the classical ANCOVA for a continuous response. From this
      relationship we demonstrate that Koch's method cannot preserve the probability of
      the type I error. Simulations with continuous responses as well as with binary
      outcomes confirm the aforementioned theoretical result on the performance of
      Koch's method under the null hypothesis of no treatment effect. However, this
      poses only a problem for relatively small to moderate sample sizes. Further, as
      specified in the original paper of Koch et al., the first approach does preserve
      the type I error for any sample size, as the P-values can be reported in an exact
      manner (Statist. Med. 1998; 17: 1863-1892). Finally, we propose a correction
      factor for Koch's test statistic that better preserves the type I error.

PMID- 14652863
TI  - Comparing Cox and parametric models in clinical studies.
AB  - Parametric models are only occasionally used in the analysis of clinical studies
      of survival although they may offer advantages over Cox's model. In this paper,
      we report experiences that we have made fitting parametric models to data sets
      from different clinical trials mainly performed at the Vienna University Medical
      School. We emphasize the role of residuals for discriminating among candidate
      models and judging their goodness of fit. The effect of misspecification of the
      baseline distribution on parameter estimates and testing has been explored. The
      results from parametric analyses have always been contrasted with those from
      Cox's model.

PMID- 14652864
TI  - Use of incomplete post-treatment data in the analysis of viral eradication
      studies.
AB  - In some studies of chronic viral infections where the objective is to estimate
      the distributions of time until viral eradication and viral resistance to
      treatment, patients must have treatment terminated in order to assess eradication
      status. Such patients then have their viral load continually monitored during a
      post-treatment period. If no virus is detected during this period, viral
      eradication is presumed to have occurred whereas detection of virus is
      interpreted to mean that the virus had been suppressed but not eradicated prior
      to treatment interruption. If the post-treatment period is long, as would be the
      case with diseases such as hepatitis C and HIV, there will be patients who have
      not completed the post-treatment period by the time the data are analysed. This
      paper proposes non-parametric and semi-parametric methods to incorporate partial
      post-treatment data in the estimation of the subdistributions of the time until
      eradication and resistance. The new methods extend previous methods for the
      analysis of eradication studies that do not account for incomplete post-treatment
      information, and are illustrated with data from a recent hepatitis C clinical
      trial.

PMID- 14652865
TI  - Sensitivity studies for quantitative assays: use of censored data analysis.
AB  - Probit regression analysis is frequently used to study the relation between the
      concentration of an analyte in a sample and the probability that the assay used
      yields a positive test result. For these analyses only the qualitative
      classification 'positive' or 'negative' is used, whereas, particularly in the
      case where the assay is quantitative in nature, the results contain more
      information. In the current paper, we propose an alternative method, in which the
      negative test results are treated as being (left) censored. As such, more
      efficient use is made of the information in the data. The procedures are
      illustrated using two generations of NucliSens assays (BioMerieux), which are
      designed to quantify the viral load of HIV-1 in blood samples. Computer
      simulations are used to illustrate some properties of the estimated parameters.

PMID- 14652866
TI  - Analysis of growth curves via mixtures.
AB  - We present a method for analysing growth curves using the mixtures-of-experts
      (ME) approach, which enables flexible estimation of the dependence of height on
      age. Individual growth curves are first fitted and the resulting estimates are
      then pooled to facilitate the estimation of mean growth curves, velocity and
      acceleration of growth and centile curves. The method allows for comparisons
      between males and females. We illustrate our methodology with data on growth of
      male and female children (0-4 years old).

PMID- 14652867
TI  - Median regression for longitudinal data.
AB  - We review and compare three estimators of median regression in linear models with
      longitudinal data. The estimators are constructed based on well-known ideas of
      weighting, decorrelating, and the working assumption of independence. Both
      asymptotic efficiency calculations and finite-sample Monte Carlo studies are used
      to assess the performance of these estimators. We find that their relative
      performances depend on the nature of covariates. The estimator under the working
      assumption of independence is computationally simple and yet has good relative
      performance when the covariates are invariant over time or when the within
      subject correlations are small. Its relative performance in finite samples is
      also found to be more favourable than suggested by the asymptotic comparisons.

PMID- 14652868
TI  - Comparison of multiple regression to two latent variable techniques for
      estimation and prediction.
AB  - In the areas of epidemiology, psychology, sociology, and other social and
      behavioural sciences, researchers often encounter situations where there are not
      only many variables contributing to a particular phenomenon, but there are also
      strong relationships among many of the predictor variables of interest. By using
      the traditional multiple regression on all the predictor variables, it is
      possible to have problems with interpretation and multicollinearity. As an
      alternative to multiple regression, we explore the use of a latent variable model
      that can address the relationship among the predictor variables. We consider two
      different methods for estimation and prediction for this model: one that uses
      multiple regression on factor score estimates and the other that uses structural
      equation modelling. The first method uses multiple regression but on a set of
      predicted underlying factors (i.e. factor scores), and the second method is a
      full-information maximum-likelihood technique that incorporates the complete
      covariance structure of the data. In this tutorial, we will explain the model and
      each estimation method, including how to carry out prediction. A data example
      will be used for demonstration, where respiratory disease death rates by county
      in Minnesota are predicted by five county-level census variables. A simulation
      study is performed to evaluate the efficiency of prediction using the two latent
      variable modelling techniques compared to multiple regression.

PMID- 14652869
TI  - Bayesian approaches to multiple sources of evidence and uncertainty in complex
      cost-effectiveness modelling.
AB  - Increasingly complex models are being used to evaluate the cost-effectiveness of
      medical interventions. We describe the multiple sources of uncertainty that are
      relevant to such models, and their relation to either probabilistic or
      deterministic sensitivity analysis. A Bayesian approach appears natural in this
      context. We explore how sensitivity analysis to patient heterogeneity and
      parameter uncertainty can be simultaneously investigated, and illustrate the
      necessary computation when expected costs and benefits can be calculated in
      closed form, such as in discrete-time discrete-state Markov models. Information
      about parameters can either be expressed as a prior distribution, or derived as a
      posterior distribution given a generalized synthesis of available data in which
      multiple sources of evidence can be differentially weighted according to their
      assumed quality. The resulting joint posterior distributions on costs and
      benefits can then provide inferences on incremental cost-effectiveness, best
      presented as posterior distributions over net-benefit and cost-effectiveness
      acceptability curves. These ideas are illustrated with a detailed running example
      concerning the cost-effectiveness of hip prostheses in different age-sex
      subgroups. All computations are carried out using freely available software for
      conducting Markov chain Monte Carlo analysis.

PMID- 14652870
TI  - Stiefel-manifold learning by improved rigid-body theory applied to ICA.
AB  - In previous contributions we presented a new class of algorithms for orthonormal
      learning of a linear neural network with p inputs and m outputs, based on the
      equations describing the dynamics of a massive rigid frame in a submanifold of
      R(p). While exhibiting interesting features, such as intrinsic numerical
      stability, strongly binding to the orthonormal submanifolds, and good
      controllability of the learning dynamics, tested on principal/independent
      component analysis, the proposed algorithms were not completely satisfactory from
      a computational-complexity point of view. The main drawback was the need to
      repeatedly evaluate a matrix exponential map. With the aim to lessen the
      computational efforts pertaining to these algorithms, we propose here an
      improvement based on the closed-form Rodriguez formula for the exponential map.
      Such formula is available in the p = 3 and m = 3 case, which is discussed with
      details here. In particular, experimental results on independent component
      analysis (ICA), carried out with both synthetic and real-world data, help
      confirming the computational gain due to the proposed improvement.

PMID- 14652871
TI  - Entropy learning and relevance criteria for neural network pruning.
AB  - In this paper, entropy is a term used in the learning phase of a neural network.
      As learning progresses, more hidden nodes get into saturation. The early creation
      of such hidden nodes may impair generalisation. Hence an entropy approach is
      proposed to dampen the early creation of such nodes by using a new computation
      called entropy cycle. Entropy learning also helps to increase the importance of
      relevant nodes while dampening the less important nodes. At the end of learning,
      the less important nodes can then be pruned to reduce the memory requirements of
      the neural network.

PMID- 14652872
TI  - A robust subspace algorithm for principal component analysis.
AB  - We present a noise robust PCA algorithm which is an extension of the Oja subspace
      algorithm and allows tuning the noise sensitivity. We derive a loss function
      which is minimized by this algorithm and interpret it in a noisy PCA setting.
      Results on the local stability analysis of this algorithm are given and it is
      shown that the locally stable equilibria are those which minimize the loss
      function.

PMID- 14652873
TI  - The nonlinear predictability of the electrotelluric field variations data
      analyzed with support vector machines as an earthquake precursor.
AB  - This work investigates the nonlinear predictability of the Electro Telluric Field
      (ETF) variations data in order to develop new intelligent tools for the difficult
      task of earthquake prediction. Support Vector Machines trained on a signal window
      have been used to predict the next sample. We observe a significant increase at
      this short-term unpredictability of the ETF signal at about two weeks time period
      before the major earthquakes that took place in regions near the recording
      devices. The unpredictability increase can be attributed to a quick time
      variation of the dynamics that produce the ETF signal due to the earthquake
      generation process. Thus, this increase can be taken into advantage for signaling
      for an increased possibility of a large earthquake within the next few days in
      the neighboring region of the recording station.

PMID- 14652875
TI  - A SOM projection technique with the growing structure for visualizing high
      dimensional data.
AB  - The Self-Organizing Map (SOM) is an efficient tool for visualizing high
      dimensional data. In this paper, an intuitive and effective SOM projection method
      is proposed for mapping high-dimensional data onto the two-dimensional grid
      structure with a growing self-organizing mechanism. In the learning phase, a
      growing SOM is trained and the growing cell structure is used as the baseline
      framework. In the ordination phase, the new projection method is used to map the
      input vector so that the input data is mapped to the structure of the SOM without
      having to plot the weight values, resulting in easy visualization of the data.
      The projection method is demonstrated on four different data sets, including a
      118 patent data set and a 399 checical abstract data set related to polymer
      cements, with promising results and a significantly reduced network size.

PMID- 14652874
TI  - Binary neural network training algorithms based on linear sequential learning.
AB  - A key problem in Binary Neural Network learning is to decide bigger linear
      separable subsets. In this paper we prove some lemmas about linear separability.
      Based on these lemmas, we propose Multi-Core Learning (MCL) and Multi-Core Expand
      and-Truncate Learning (MCETL) algorithms to construct Binary Neural Networks. We
      conclude that MCL and MCETL simplify the equations to compute weights and
      thresholds, and they result in the construction of simpler hidden layer. Examples
      are given to demonstrate these conclusions.

PMID- 14652876
TI  - Novel stability criteria for delayed cellular neural networks.
AB  - In this paper, a new sufficient condition is given for the global asymptotic
      stability and global exponential output stability of a unique equilibrium points
      of delayed cellular neural networks (DCNNs) by using Lyapunov method. This
      condition imposes constraints on the feedback matrices and delayed feedback
      matrices of DCNNs and is independent of the delay. The obtained results extend
      and improve upon those in the earlier literature, and this condition is also less
      restrictive than those given in the earlier references. Two examples compared
      with the previous results in the literatures are presented and a simulation
      result is also given.

PMID- 14652877
TI  - Legal regulation of the Croatian Medical Journal: model for small academic
      journals.
AB  - During the last few years, the questions of editorial independence and journal
      governance have come into the focus of scholarly journals. There is little data
      on the legal regulation of journals outside mainstream science, although they
      constitute the largest body of biomedical literature. The Croatian Medical
      Journal functioned for more than 10 years without much legal regulation but with
      lot of enthusiasm and hard work. This Editorial presents our attempt to make
      legal provisions for the current status of the Journal and its future work. We
      defined our owners, main participants in making of the journal, and their
      responsibilities and benefits. The Agreement will be signed by all four medical
      schools in Croatia, which will become owners of the Journal. We hope that our
      experiences and solutions for strengthening the legal status of the Journal will
      help other editors from small scientific communities to think about their journal
      and its governance.

PMID- 14652878
TI  - Severe Acute Respiratory Syndrome (SARS): loud clang of the Leper's bell.
AB  - Severe acute respiratory syndrome (SARS) or the "Chinese Chernobyl" emerged
      against an alarming background of rising infectious disease in poor rural China
      and to a backdrop of interregional and global polarization of population well
      being and vulnerability. SARS has added its own dissonant note to "health
      disturbance", caused fear and panic and disrupted international commerce. Its
      emergence should be perceived as a disturbing alarm that underscores the need to
      strengthen public health and facilitate construction of a human security
      "umbrella" in the event of future disasters. Although SARS has produced a
      relatively insignificant level of damage when compared to other threats, its long
      term effects on health should not be underestimated, based on its unexpected
      appearance and still unknown properties. This essay presents a qualitative
      flowchart that follows SARS from its origin in China to the accumulation of
      global damage. Two future scenarios were formulated, covering a worse-case
      outcome and containment outcome, which currently appears to be the case. In the
      event of the worst-case scenario it is doubtful whether any health service in
      Europe could cope. In either case, the development of a European Union Center for
      Disease Control is mandatory.

PMID- 14652879
TI  - Journal publications from Zagreb University Medical School in 1995-1999.
AB  - AIM: To analyze a five-year publication output of the Zagreb University Medical
      School in scientific journals, especially in the journals covered by the Current
      Contents (CC), bibliographic database of the Institute for Scientific
      Information. METHODS: Medical School of the Zagreb University is organized in 10
      preclinical, 6 public health, and 17 clinical departments, with 359 faculty
      members. Research activity is important for the academic promotion, with the
      number of publications (especially in journals covered by CC) and their impact as
      a key element. Bibliographic data on the published papers by the authors
      affiliated to the Zagreb University Medical School in the 1995-1999 period were
      searched in the CC and Biomedicina Croatica databases, according to the official
      faculty name list. The collected data were classified into three groups according
      to the source journals: papers published in international journals covered by the
      CC, Croatian journals covered by the CC, and Croatian journals not covered by the
      CC. The publication production was measured on individual and departmental levels
      by using two counting schemes: a) full publication to each author/department; and
      b) an equal fraction of a publication (1/n) to each author/department. RESULTS:
      In the 1995-1999 period, the faculty published 578 papers in the journals covered
      by the CC, 22.6% of them in the subset of Croatian journals. The differences
      among departments were considerable, with publishing activity per faculty member
      varying from 0.25 to 6.23 papers in CC journals and from 0.0 to 15.8 in Croatian
      non-CC journals. Preclinical departments published significantly less in the
      Croatian journals indexed in the CC then public health and clinical departments.
      There was a high variance in the number of publications on the individual level,
      with the 15.4% of the faculty in the professor rank and 45% in the assistant rank
      who did not publish a single paper in journals covered by the CC in the analyzed
      period. On the contrary, 10.1% of professors and 6.0% of assistants published
      more than 10 and more than 4 CC-indexed papers, respectively. A number of authors
      who have been very productive in international journals indexed in the CC (11 or
      more papers) did not publish in Croatian journals indexed in the same database,
      and vice versa. CONCLUSION: Publication output of the Zagreb University Medical
      School shows imbalances characteristic of a small scientific community:
      productivity with extreme values, relatively unsatisfactory number of papers
      published in the international journals covered by the CC database as compared to
      their importance in the process of the academic promotion, and disproportional
      role of certain domestic journals covered by the CC.

PMID- 14652880
TI  - Comparison of protective effects of catechin applied in vitro and in vivo on
      ischemia-reperfusion injury in the isolated rat hearts.
AB  - AIM: To determine overall cardiac effects of flavonoid catechin on ischemia
      reperfusion injury in isolated rat hearts in vitro and in vivo. METHODS: After
      perfusing hearts at the pressure of 70 mm Hg, coronary perfusion was interrupted
      for 30 minutes and then re-established. There were four experimental groups, with
      10 rats each. The first group received 100 micromol/L of catechin added to the
      perfusate 10 minutes before, during, and 10 minutes after ischemia; the second
      group underwent in vivo pretreatment with catechin (250 mg/kg body weight)
      applied intragastrically for 10 days; the third group received it as a single
      dose 1 h before sacrifice; and the fourth group received saline. An additional
      group of 10 hearts served as untreated, nonischemic time control. The variables
      included heart rate, atrioventricular conduction time, cardiac rhythm,
      isovolumetric left ventricular pressure, coronary flow and responsiveness, oxygen
      consumption, relative cardiac efficiency, lactate dehydrogenase release, and
      myocardial lipid peroxidation. RESULTS: Catechin added to the perfusate increased
      the coronary flow and ratio of oxygen delivery to myocardial oxygen consumption
      before ischemia and during reperfusion. Following 30 minutes of reperfusion,
      isovolumetric left ventricular developed pressure recovered to 42+/-3%, 63+/-3%,
      71+/-2%, and 55+/-3% of the initial control values in the control, catechin 1 h,
      catechin for 10 days, and catechin in vitro group, respectively. Cardiac
      efficiency and coronary responsiveness were also best preserved in the group
      receiving catechin for 10 days. CONCLUSION: Application of catechin in vitro and
      in vivo, irrespective of duration of application, resulted in cardioprotection
      against ischemia-reperfusion injury, but long-term pretreatment provided more
      favorable effects. Directly applied, catechin acted as a vasodilator.

PMID- 14652881
TI  - Multiple sclerosis with uncommon cerebrospinal fluid findings.
AB  - AIM: To determine the frequency and clinical and laboratory features of patients
      with multiple sclerosis characterized by uncommon cerebrospinal findings, ie,
      negative oligoclonal band or increased number of mononuclear cells in
      cerebrospinal fluid. METHODS: The retrospective analysis included medical records
      of 233 patients (158 women and 75 men) admitted to the Department of Neurology,
      Ljubljana Medical Center, between January 1, 1990, and December 31, 1999 and
      discharged with the diagnosis of multiple sclerosis. We determined clinical
      features and cerebrospinal fluid parameters of patients with oligoclonal band
      negative multiple sclerosis and > or =15 mononuclear cells/mm( 3) in
      cerebrospinal fluid and compared them with patients with oligoclonal band
      positive multiple sclerosis and expected number of mononuclear cells in
      cerebrospinal fluid, respectively. There were 26 patients with oligoclonal band
      negative finding and 26 with > or =15 mononuclear cells/mm(3) in cerebrospinal
      fluid. The two groups of patients did not overlap, except for one patient, who
      had 19 mononuclear cells/mm(3) and was oligoclonal band-negative. RESULTS: The
      diagnosis was delayed in oligoclonal band-negative multiple sclerosis patients,
      their cerebrospinal fluid contained less leukocytes, and lower concentration of
      IgG. The patients with > or =15 leukocytes/mm( 3) in cerebrospinal fluid were
      diagnosed earlier and had increased cerebrospinal fluid protein and IgG
      concentrations. CONCLUSION: Multiple sclerosis with negative oligoclonal band or
      increased count of leukocytes in cerebrospinal fluid were found in approximately
      10% of patients with the disease. Because of the absence of oligoclonal band and
      less active cerebrospinal fluid, the diagnosis in these patients may be delayed.

PMID- 14652882
TI  - Center for Disease Control (CDC) flow cytometry panel for human immunodeficiency
      virus infection allows recognition of infectious mononucleosis caused by Epstein
      Barr virus or cytomegalovirus.
AB  - AIM: To analyze the distribution of lymphocyte subsets in the peripheral blood of
      patients with infectious mononucleosis caused by Epstein-Barr virus (EBV) and
      cytomegalovirus (CMV) and to investigate the possible diagnostic usefulness of
      flow cytometry panel recommended by the Center for Disease Control and Prevention
      (CDC) for HIV-1 infection. METHODS: The study included 130 immunocompetent adults
      with infectious mononucleosis caused by EBV (n=103) and CMV (n=27) and 50
      controls. EBV-infected patients were divided into two groups based on typical
      (n=92) or atypical (n=11) clinical presentation of the disease. Lymphocyte
      subpopulations were determined by flow cytometry and a panel of monoclonal
      antibodies recommended by the CDC for the immunophenotyping of patients infected
      with human immunodeficiency virus (HIV). RESULTS: Patients with typical and
      atypical presentation of EBV-induced infectious mononucleosis showed increased
      percentages of total T-cells, cytotoxic-suppressor CD8(+) T cells and activated
      HLA-DR(+) T cells compared to healthy controls. Percentages of CD4(+) T cells, as
      well as CD4/CD8 ratio, were significantly decreased. Absolute counts of CD4(+) T
      cells and percentages of B cells did not differ from healthy controls. Pattern of
      changes in CMV-infected patients was completely identical to that in healthy
      controls, although less pronounced. CONCLUSION: Lymphocyte subpopulations
      represented in the CDC panel for HIV are sufficient for the recognition of
      patients with infectious mononucleosis caused by EBV and CMV. Flow cytometry can
      be useful support for reaching diagnosis in patients with atypical clinical
      presentation of EBV-induced infectious mononucleosis.

PMID- 14652883
TI  - Demonstration of apoptosis-associated cleavage products of DNA, complement
      activation products SC5b-9 and C3d/dg, and immune complexes CIC-C3d, CIC-IgA, and
      CIC-IgG in the urine of patients with membranous glomerulonephritis.
AB  - AIM: To investigate the involvement of complement activation and apoptosis in the
      pathogenesis of membranous glomerulonephritis by determining the concentrations
      of apoptosis-associated 180 bp nucleosomes and complement activation products
      SC5b-9 and C3d/dg in the urine of patients with membranous glomerulonephritis.
      METHODS: Morning urine was taken from 15 patients with immunohistologically
      established membranous glomerulonephritis. Apoptosis-associated 180 bp
      nucleosomes, complement activation products SC5b-9, C3d/dg, and immune complexes
      CIC-C3d, CIC-IgA, and CIC-IgG were detected in the urine samples by using antigen
      specific enzyme-linked immunosorbent assay. RESULTS: Concentrations of measured
      parameters were expressed in units of standard deviation, ie, relatively to the
      average concentrations measured in healthy subjects. We found drastically
      increased concentrations of apoptosis-associated 180 bp nucleosomes (13.71+/
      14.97; p=0.047), complement activation products SC5b-9 (197.07+/-134.88; p=0.003)
      and C3d/dg (38.70+/-43.35; p=0.048), and immune complexes CIC-C3d (11.01+/-13.39;
      p=0.74), CIC-IgA (7.93+/-4.38; p=0.001), and CIC-IgG (20.56+/-10.87; p=0.001) in
      the urine of patients with an active form of membranous glomerulonephritis. All
      studied molecules were absent, or present in very low concentrations, in healthy
      subjects and patients with membranous glomerulonephritis in remission. The mean
      differences between healthy controls and patients with the active disease were
      statistically significant in all parameters, except CIC-C3d. CONCLUSIONS: There
      is an association of complement activation and apoptosis with membranous
      glomerulonephritis. Correlation analysis suggests that the excretion of apoptosis
      associated 180 bp nucleosomes, SC5b-9, C3d/dg, and immune complexes containing
      IgA and IgG in the urine of patients with active membranous glomerulonephritis
      does not depend solely on the passive transport together with other proteins, but
      is probably an independent active process.

PMID- 14652884
TI  - Management of cardiovascular risk factors in type 2 diabetic patients undergoing
      coronary angiography.
AB  - AIM: To investigate risk factor management in diabetic patients undergoing
      coronary angiography. METHODS: Hemoglobin (Hgb) A1c, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides
      (TG), blood pressure (BP), and body mass index (BMI) were cardiovascular risk
      factors analyzed in 284 consecutive type 2 diabetic patients who underwent
      coronary angiography. RESULTS: Coronary artery disease (CAD) was identified in
      233 (82.0%) diabetic patients. The mean HgbA1c fraction for all patients at
      hospital admission was 9.7+/-1.4%. The mean concentration of LDL-C, HDL-C, and
      triglycerides was 2.82+/-0.9, 0.92+/-0.28, and 2.56+/-0.81 mmol/L, respectively.
      One hundred and twenty-two (43.0%) patients had LDL-C <2.6 mmol/L, 70 (24.7%)
      patients had a blood pressure of less than 130/85 mm Hg, and 158 (55.7%) had BMI
      <30 kg/m(2). Only 26 (9.1%) patients had optimal control of the above cardiac
      risk factors. The average LDL-C, triglycerides, and blood pressure in patients
      with severe coronary artery disease were higher than those in patients with
      moderate to mild coronary artery disease (p<0.01; unpaired t-test). CONCLUSIONS:
      Cardiovascular risk factors were poorly controlled in type 2 diabetic patients.
      The average LDL-C, triglycerides, and blood pressure in patients with severe
      coronary artery disease were higher than those in patients with moderate to mild
      coronary artery disease.

PMID- 14652885
TI  - Prilocaine versus plain or buffered lidocaine for local anesthesia in laceration
      repair: randomized double-blind comparison.
AB  - AIM: To compare the effectiveness of 2% prilocaine plain solution, 1% lidocaine
      hydrochloride, and 1% buffered lidocaine in local anesthesia and pain reduction
      during injection in laceration repair. METHODS: A double-blind randomized
      prospective comparison study included 183 consecutive eligible adult patients
      with simple lacerations, admitted to the emergency department between January
      2001 and June 2002. Each of the three groups of patients received different local
      anesthetic before laceration suturing (1% lidocaine, 2% prilocaine, or buffered
      1% lidocaine). The patients were asked to assess the pain intensity on a 0-100
      numerical rating scale at the site of needle entry into the skin (P1),
      immediately after the completion of injection (P2), and after the first puncture
      of the suturing needle (P3). The differences among the three patient groups were
      tested with one-way analysis of variance and chi-square test. RESULTS: The three
      groups of 61 patients each (one patient declined from prilocaine group) did not
      significantly differ in mean P1 scores (29.1+/-20.9 in the prilocaine, 32.2+/
      22.9 in the lidocaine, and 33.2+/-21.7 in the buffered lidocaine group; p=0.56).
      Mean P2 scores were highest in the prilocaine group (24.0+/-16.0), followed by
      lidocaine (20.9+/-14.9) and buffered lidocaine (16.1+/-11.3) groups (p=0.007).
      Mean P3 score was significantly lower in the lidocaine group (13.4+/-11.3) then
      in the prilocaine (18.4+/-13.1) and buffered lidocaine (20.4+/-16.2) groups
      (p=0.014). The number of patients who required additional anesthetic
      administration in each group was not significantly different (p=0.09).
      CONCLUSION: Injection of 1% lidocaine was associated with lower pain ratings on
      suturing needle puncture than with 2% prilocaine or buffered 1% lidocaine.

PMID- 14652886
TI  - Predictive value of assessment of general movements for neurological development
      of high-risk preterm infants: comparative study.
AB  - AIM: To assess the predictive value of normal, abnormal, or absent general
      movements in high-risk preterm infants for the later neurological development.
      METHODS: The study involved 120 high-risk preterm infants (gestational age, < or
      =37 weeks) having at least three or more antenatal, perinatal, or neonatal risk
      factors for impaired neurological development, and 112 age-matched controls. The
      method of general movements of fidgety character assessment was compared with
      classical neurological examinations performed longitudinally until the corrected
      age of two years. The age-adequate neurological examinations based on the
      criteria by Amiel-Tison and Grenier and Illingworth were used. Specialists in
      clinical psychology also monitored the child's development. The results of
      specialists' examinations were taken into account. RESULTS: Out of 83 high-risk
      preterm infants with normal fidgety movements, 81 (97%) had a normal neurological
      outcome. Abnormal or absent fidgety movements were followed by abnormal
      neurological outcome in 30 (81%) out of 37 infants. Cerebral palsy was diagnosed
      in 13 children, mental retardation in one, whereas 16 children had both cerebral
      palsy and mental retardation. The validity of the general movement assessment was
      92%, sensitivity 94%, specificity 92%, positive predictive value 81%, and
      negative predictive value 98%. These values were better than those of the
      classical neurologic examination (60%, 97%, 43%, 44%, and 97%, respectively).
      CONCLUSION: The method of general movement assessment had significantly better
      validity, sensitivity, specificity, positive, and negative predictive value than
      classical neurological examination of high-risk preterm infants.

PMID- 14652887
TI  - Obstetric risk factors associated with placenta previa development: case-control
      study.
AB  - AIM: To evaluate potential risk factors and perinatal outcome of pregnancies
      complicated with placenta previa in Croatian population of pregnant women
      recruited from the largest tertiary care perinatal center in Croatia. METHODS:
      This retrospective case-control study included a total of 202 singleton
      pregnancies with placenta previa during a 10-year study period and 1,004 randomly
      selected simple singleton controls. Data on potential risk factors for placenta
      previa development were carefully extracted from medical records, reviewed, and
      compared with a control group of women. Data were statistically analyzed with chi
      square test and Mann-Whitney U test, and crude odds ratio (OR) with 95%
      confidence interval (95% CI) were provided. RESULTS: The incidence of placenta
      previa was 0.4%. Factors significantly associated with a placenta previa
      development were advanced maternal age (especially >34 years, even after
      adjustment for high parity), gravidity of 3 and more (OR, 4; 95% CI, 2.5-6.6),
      more than one previous delivery (OR, 2.76; 95% CI, 1.7-4.3), history of previous
      cesarean sections (OR, 2.0; 95% CI, 1.17-3.44), abortions (OR, 2.8; 95% CI, 2.04
      3.83), and presence of various uterine abnormalities (OR, 8.5; 95% CI, 1.75
      44.5). The risk was significantly increased after two previous cesarean sections
      (OR, 7.32; 95% CI, 2.1-25) and after one previous abortion (OR, 4.8; 95% CI, 2.7
      8.3). No difference between the groups was found regarding the history of
      previous placenta previa, drug abuse, and male sex at birth. Smoking history was
      significantly less frequent in women with placenta previa than controls (16.3% vs
      25.6%, chi-square=7.9, p=0.007). The main perinatal complication was preterm
      birth, with 14-fold higher risk in women with placenta previa. Preterm infants of
      mothers with placenta previa were more likely to have lower first- (6 vs 10,
      p<0.001) and fifth-minute median Apgar scores (8 vs 10, p<0.045). Term infants of
      mothers with placenta previa had significantly lower birth weight then their
      controls (3,300 vs 3,500 g, p<0.001). CONCLUSION: The most important obstetric
      factors for placenta previa development were advanced maternal age especially >34
      years, 3 or more previous pregnancies, parity of 2 and more, rising number of
      previous abortions, and history of previous cesarean section, but not child sex
      at birth, history of drug abuse and previous placenta previa. Smoking cigarettes
      was significantly less frequent in women with placenta previa. Preterm delivery
      still remains the greatest problem in pregnancies complicated with placenta
      previa.

PMID- 14652888
TI  - Monochorionic twin pregnancy: retrospective analysis of predicted pregnancy
      outcome.
AB  - AIM: To assess the accurate establishment of chorionicity, perinatal
      complications, and outcome of monochorionic twin pregnancies managed in a
      tertiary referral center in Croatia and compare the findings with data published
      for other countries. METHODS: The retrospective analysis included data on a total
      of 24 monochorionic twin pregnancies delivered at the Department between January
      1998 and May 2002. The data retrieved from the maternity ward birth register
      included the ultrasound establishment of chorionicity, demographic data,
      complications of the pregnancy (presence of twin-to-twin-transfusion syndrome,
      intrauterine growth restriction, and threatened or actual preterm labor rate),
      and pregnancy outcome. Perinatal morbidity and mortality were also analyzed.
      RESULTS: The establishment of chorionicity by ultrasound was accurate in all 24
      monochorionic twin pregnancies. Five twins died in the perinatal period, and two
      in early neonatal period. The median gestational age at delivery was 35 weeks,
      ranging 29 to 38 weeks, and median birth weight was 1,990 g, ranging from 740 to
      3,000 g. Intrauterine growth restriction was present in 18 cases, whereas twin-to
      twin-transfusion syndrome complicated 2 monochorionic twin pregnancies. Symptoms
      of threatened preterm labor were present in 19 women, whereas actual preterm
      delivery rate was 16 out of 24. CONCLUSION: The diagnosis of monochorionic twin
      pregnancy can be reliably made by ultrasound. Monochorionic twin pregnancies are
      characterized by a high complication rate, with threatened and actual preterm
      labor and delivery as the most common complications. These pregnancies are also
      accompanied with high perinatal mortality and morbidity.

PMID- 14652889
TI  - Conservative treatment of extra-articular Colles' type fractures of the distal
      radius: prospective study.
AB  - AIM: To determine the anatomical and functional results of conservative treatment
      of extra-articular Colles' type fractures of the distal radius and the borderline
      value of each anatomical parameter for the best possible correlation with
      functional end result. METHODS: This prospective study included 54 patients.
      Standard radiographs were made of both wrists in two directions after the
      fracture, then of the injured side on day 11 following repositioning, and finally
      of the union of bone segments. Anatomical results were assessed by evaluating the
      dorsal angulation, loss of radial inclination, and loss of radial length.
      Functional results were assessed by the evaluation of pain, range of active
      motion, grip strength, and appearance of the wrist joint. RESULTS: Statistically
      significant association was found between the anatomical and functional results
      (chi-square=16.3, p<0.001). Excellent or good anatomical and functional results
      were obtained in 24 patients, whereas in 30 patients both treatment outcomes were
      assessed as fair or poor. If < or=10 degrees of dorsal angulation was taken as a
      borderline value for a good outcome, there was significant association with a
      good functional result (chi-square=23.6, p<0.001). However, if < or=9 degrees
      loss of radial inclination was taken as a borderline value for a good outcome, no
      association with a good functional result was found (chi-square=3.9, p=0.530). If
      < or=6 mm of radial shortening was taken as a borderline value for a good
      outcome, again no association existed with a good functional result (chi
      square=6.43, p=0.011). CONCLUSION: We found an association between anatomical and
      functional results after conservative treatment of extra-articular Colles' type
      fracture of the distal radius. Acceptable borderline dorsal angulation was < or=9
      degrees; acceptable loss of radial inclination was < or=3 degrees, and acceptable
      loss of radial length was < or=2 mm.

PMID- 14652890
TI  - Primary vs secondary wound reconstruction in Gustilo type III open tibial shaft
      fractures: follow-up study of 35 cases.
AB  - AIM: To compare primary and secondary wound reconstruction as a treatment method
      for Gustilo type III open tibial fractures. METHODS: Thirty-five consecutive
      patients with a Gustilo type III open tibial shaft fracture were treated and
      followed up for 3 years. The patients were divided into two groups depending on
      the treatment protocol and timing of wound reconstruction: primary wound
      reconstruction (n=15) and secondary wound reconstruction (n=20). After
      determining median value, the variability was expressed with the 25th and 75th
      percentiles. RESULTS: In the primary wound reconstruction group, healing was
      achieved in 13 out of 15 patients. The median time to recovery was 68 (25th-75th
      percentile=32-86) weeks, median number of operations was 4 (25th-75th
      percentile=3-5), and median Johner and Wruhs score was 4 (25th-75th percentile=3
      5). There were 9 cases with a bone defect and 2 tibial amputations were
      performed. In the secondary wound reconstruction group, complete recovery was
      achieved in 18 out of 20 patients. The median time to recovery was 115.5 (25th
      75th percentile=70.0-128.5) weeks, median number of operations 7.5 (25th-75th
      percentile=6.5-8.5), and median score according to Johner and Wruhs' criteria 3
      (25th-75th percentile=2-4). There were 19 cases with a bone defect and 1 tibial
      amputation was performed. Chronic osteomyelitis persisted only in a single
      patient. Median time to recovery and number of operations were significantly
      smaller in patients undergoing primary wound reconstruction. CONCLUSION: Primary
      wound reconstruction required smaller number of operations and shorter time to
      recovery than secondary wound reconstruction, mostly due to a significantly
      smaller proportion of cases with a bone defect.

PMID- 14652891
TI  - Exposure levels and skin reactivity to German cockroach (Blattella germanica) in
      Croatia.
AB  - AIM: To evaluate German cockroach (Blattella germanica) allergen levels in house
      dust and skin reactivity to German cockroach in adult atopic and non-atopic
      subjects in inland areas of Croatia. METHODS: Blattella germanica group 2 (Bla g
      2) allergen was measured using the enzyme-linked immunosorbent assay (ELISA) on
      test strips (Dustscreen(TM) test, Heska AG, Switzerland) in 94 house dust samples
      collected from living room and bedroom floors, 35 from rural and 59 from urban
      areas. Skin prick testing with common inhalatory allergens, Blatella germanica,
      storage mites Lepidoglyphus destructor and Tyrophagus putrescentiae (ALK-Abello,
      Denmark) was performed in 187 adult outpatients, 131 from urban and 56 from rural
      areas. Total serum IgE levels were measured using the ELISA method. Subjects with
      relevant respiratory and/or skin symptoms, at least one positive skin prick test,
      and/or increased total IgE were considered atopic. RESULTS: Positive skin prick
      test to cockroach was observed in 18/187 subjects (9.6%). The frequency of skin
      prick test positive subjects to cockroach was higher in atopic than in non-atopic
      subjects, but not significantly (12.2% vs. 4.7%; p=0.098). Of 15 atopic subjects
      with positive skin prick test to cockroach, 14 also had positive skin prick test
      to storage mites, 8 to house dust mites, 1 to pollens, and none to cockroach
      only. Positive skin prick test to storage mites was the only factor which
      significantly increased the risk for having positive skin prick test to cockroach
      (n=187; odds ratio, 109.82; 95% confidence interval, 2.06- 5853.5; p= 0.020). In
      all 94 house dust samples, Bla g 2 was not detectable. CONCLUSIONS: Our results
      suggest that there is no relevant exposure to cockroach allergen in house dust
      samples from inland areas of Croatia. Consequently, positive skin prick test to
      cockroach is rare in adult subjects, even in atopics. Positive skin prick test to
      cockroach in atopics is in the majority of cases related to positive skin prick
      test to storage mites, probably due to cross-reactivity.

PMID- 14652892
TI  - Neglected case of osteoarticular Brucella infection of the knee.
AB  - A 49-year-old farmer had a history of recurrent knee effusion for 20 years. He
      did not report undergoing any diagnostic or therapeutic procedures apart from
      repeated aspirations of the joint fluid. After the isolation of Brucella
      melitensis from the joint fluid, computed tomography-guided bone biopsy was
      performed and histopathologic examination of the biopsy sample confirmed the
      diagnosis of chronic Brucella osteomyelitis. Arthroscopic synovectomy combined
      with antimicrobial therapy with doxycyclin, rifampicin, and ciprofloxacin for six
      months resulted in clinical recovery. This case indicates that brucellosis should
      be suspected in patients with non-specific and chronic osteoarticular symptoms,
      especially in endemic regions.

PMID- 14652893
TI  - Intra-articular calcaneal fracture in a 14-year-old competing skier: case report.
AB  - Intra-articular calcaneal fracture as a skiing injury in children is extremely
      rare. We report on what we believe is a unique and previously unreported
      mechanism of a skiing injury, which caused intra-articular calcaneal fracture in
      a young competing skier, a member of the Croatian national ski team. This 14-year
      old boy sustained a heel injury while training for giant slalom. There was no
      fall on the heel or obvious axial force that could have caused this type of
      calcaneal fracture. The skier had sophisticated equipment and used carving skies.
      We speculated that, when the skier tried to establish the lost balance during the
      fall, a violent contraction of triceps muscle occurred. Instead of an injury of a
      well-protected tuber or Achilles tendon, the strong pulling force of the Achilles
      tendon was transmitted more distally and anteriorly, generating axial compression
      force, which caused an intra-articular fracture of the calcaneus bone. Obviously,
      the existing ski boot did not sufficiently protect the calcaneus bone. We
      postulate that the calcaneal tuber and Achilles tendon were protected on the
      expense of the intra-articular calcaneal fracture. Our case warns of the
      possibility of a serious foot injury in young top skiers in spite of extensive
      improvement in the ski equipment. Sophisticated carving skis could be a
      contributing factor to an injury.

PMID- 14652894
TI  - Splenic atrophy as complication of ulcerative colitis diagnosed by
      antigranulocyte antibodies labeled with Tc-99m-pertechnetate.
AB  - The scintigraphic examination with Tc-99m pertechnetate-labeled anti-NCA 95
      antigranulocyte antibodies (AGAb) was performed in a 14-year-old boy with a 7
      year history of poorly controlled ulcerative colitis to estimate the spread and
      activity of the disease. The disturbance of the splenic function was also
      suspected because Howell-Jolly bodies were present in the peripheral blood
      smears. High AGAb uptake in the rectum, sigma, and descending colon was observed
      on scintigraphy scans, indicating an active inflammatory process. Slight
      depression of hemopoiesis was also noticed. The spleen was not visible on the
      scans, although it was visible on ultrasound examination performed a few years
      earlier. Because of the refractory disease, total colectomy was performed. The
      spleen was not found on surgery. This case shows all benefits of using AGAb as a
      diagnostic tool. With a single injection we were able to show the spread and
      activity of the intestinal disease, distribution and function of the
      granulopoietic bone marrow, and absence of the spleen.

PMID- 14652895
TI  - Oranges and dead fish.

PMID- 14652896
TI  - Quality of life: an outcome of care measure. The case of multiple sclerosis.

PMID- 14652897
TI  - Ethics as a core competency in science and engineering.

PMID- 14652898
TI  - Ageism in science: fair-play between generations.
AB  - This paper discusses the role of age in scientific practice from an ethical
      perspective. In social perception, people tend to categorise others rather
      automatically along three major dimensions: race, sex, and age. Much empirical
      and theoretical attention has been devoted to the study of racism and sexism, but
      comparatively little research in the social and behavioural sciences has been
      directed at understanding what some refer to as the third '-ism': ageism. For a
      serious understanding of the implications of ageism in science, it is necessary
      to discuss, first, the conflicting relationships between classical and modern
      concepts of time and calendar age, and thereafter the concept of ageism.

PMID- 14652899
TI  - Coding ethical behaviour: the challenges of biological weapons.
AB  - Since 11 September 2001 and the anthrax attacks that followed in the US, public
      and policy concerns about the security threats posed by biological weapons have
      increased significantly. With this has come an expansion of those activities in
      civil society deemed as potential sites for applying security controls. This
      paper examines the assumptions and implications of national and international
      efforts in one such area: how a balance or integration can take place between
      security and openness in civilian biomedical research through devising
      professional codes of conduct for scientists. Future attempts to establish such
      codes must find a way of reconciling or at least addressing dilemmatic and
      tension-ridden issues about the appropriateness of research; a topic that raises
      fundamental questions about the position of science within society.

PMID- 14652900
TI  - Medical journals' conflicts of interest in the publication of book reviews.
AB  - The purpose of the study was to assess medical journals' conflicts of interest in
      the publication of book reviews. We examined book reviews published in 1999,
      2000, and 2001 (N = 1,876) in five leading medical journals: Annals of Internal
      Medicine, British Medical Journal (BMJ), Journal of the American Medical
      Association (JAMA), Lancet, and New England Journal of Medicine. The main outcome
      measure was journal publication of reviews of books that had been published by
      the journal's own publisher, that had been edited or authored by a lead editor of
      the journal, or that posed another conflict of interest. We also surveyed the
      editors-in-chief of the five journals about their policies on these conflicts of
      interests. During the study period, four of the five journals published 30 book
      reviews presenting a conflict of interest: nineteen by the BMJ, five by the
      Annals, four by JAMA, and two by the Lancet. These reviews represent 5.8%, 2.7%,
      0.7%, and 0.7%, respectively, of all book reviews published by the journals.
      These four journals, respectively, published reviews of 11.9%, 25.0%, 0.9%, and
      1.0% of all medical books published by the journals' publishers. Only one of the
      30 book reviews included a disclosure statement addressing the conflict of
      interest. None of the journals had a written policy pertaining to the conflicts
      of interest assessed in this study, although four reported having unwritten
      policies. We recommend that scientific journals and associations representing
      journal editors develop policies on conflicts of interest pertaining to book
      reviews.

PMID- 14652901
TI  - A case study of community-based participatory research ethics: the Healthy Public
      Housing Initiative.
AB  - We conducted and analyzed qualitative interviews with 12 persons working on the
      Healthy Public Housing Initiative in Boston, Massachusetts in 2001. Our goal was
      to generate ideas and themes related to the ethics of the community-based
      participatory research in which they were engaged. Specifically, we wanted to see
      if we found themes that differed from conventional research that is based on an
      individualistic ethics. There were clearly distinct ethical issues raised with
      respect to projects and individuals who engage in community-based collaborations.
      The differences that arose from the interviews were seeking equality between the
      partners, the need for the community partner to defend the community, dealing
      with unflattering data, meeting community expectations and producing tangible
      benefits to the community.

PMID- 14652902
TI  - "Things that went well--no serious injuries or deaths": ethical reasoning in a
      normal engineering design process.
AB  - We argue that considering only a few 'big' ethical decisions in any engineering
      design process--both in education and practice--only reinforces the mistaken idea
      of engineering design as a series of independent sub-problems. Using data
      collected in engineering design organisations over a seven year period, we show
      how an ethical component to engineering decisions is much more pervasive. We
      distinguish three types of ethical justification for engineering decisions: (1)
      consequential, (2) deontological or non-consequential, and (3) virtue-based. We
      find that although there is some evidence for engineering designers as 'classic'
      consequentialists, a more egocentric consequentialism would appear more fitting.
      We also explain how the idea of a 'folk ethics'--a justification in the second
      category that consciously weighs one thing with another--fits with the idea of
      the engineering design process as social negotiation rather than as technological
      progress.

PMID- 14652903
TI  - "Mind the gaps": an empirical approach to engineering ethics, 1997-2001.
AB  - A survey on ethical issues in engineering was administered over a five-year
      period to Stanford engineering students and practicing engineers. Analysis of its
      results strongly suggests that important disconnects exist between the education
      of engineering students regarding ethical issues in engineering on the one hand,
      and the realities of contemporary engineering practice on the other. Two
      noteworthy consequences of these gaps are that the views of engineering students
      differ substantially over what makes an issue an ethical issue, while practicing
      engineers exhibit significant disagreement over what is the most important non
      technical aspect of being a responsible engineering professional in contemporary
      society. These divergences impede the recognition of ethical issues and of
      specific moral responsibilities of engineers in concrete professional practice.
      It is argued that the use of suitably refined and probing surveys of engineering
      students and practicing engineers about ethical issues in engineering is an
      important although neglected empirical approach to the study of engineering
      ethics. Such an approach can enhance the prevailing case study method and combat
      over-tidy theoretical-analytical approaches to the subject.

PMID- 14652904
TI  - An effective strategy for integrating ethics across the curriculum in
      engineering: an ABET 2000 challenge.
AB  - This paper describes a one-day workshop format for introducing ethics into the
      engineering curriculum prepared at the University of Puerto Rico at Mayaguez
      (UPRM). It responds to the ethics criteria newly integrated into the
      accreditation process by the Accreditation Board of Engineering and Technology
      (ABET). It also employs an ethics across the curriculum (EAC) approach; engineers
      identify the ethical issues, write cases that dramatize these issues, and then
      develop exercises making use of these cases that are specially tailored to
      mainstream engineering classes. The different activities and strategies employed
      in this workshop are set forth. Specific references are made to the cases and
      exercises developed as a result of these workshops. The paper ends by summarizing
      the different assessments made of the workshop by addressing the following
      questions: how did it contribute to the overall ABET effort at UPRM; could other
      universities benefit from a similar activity; and how did the participants
      evaluate the workshop?

PMID- 14652905
TI  - Barking up the wrong tree? Industry funding of academic research. A case study
      with commentaries.
AB  - This case raises ethical issues involving conflicts of interest arising from
      industrial funding of academic research; ethical responsibilities of laboratories
      to funding agencies; ethical responsibilities in the management of a research
      lab; ethical considerations in appropriate research design; communication in a
      research group; communication between advisor and graduate student;
      responsibilities of researchers for the environment; misrepresentation or
      withholding of scientific results.

PMID- 14652906
TI  - Energy and sociality in human populations.
AB  - In order to characterize and define human populations from a thermodynamic point
      of view, and considering that human societies are complex systems whose global
      description can be obtained by their energetic balance, the relationship was
      evaluated between individual energy consumption and the demographic and social
      economic variables in all provinces of Spain. Pearson bivariate correlation,
      lineal regression analysis, and the coefficient of determination were applied.
      The results obtained show that individual energy consumption is associated with
      almost all the variables considered, in provinces with fewer than 400,000
      inhabitants. However, in provinces having a population larger than 400,000, the
      association is reduced to about 50 percent. The positive or negative association
      between individual energy consumption and certain variables, especially those
      that determine reproductive success, suggests that the consumption of energy is
      explained both by the irreversible thermodynamics in relatively small populations
      and by the optimization principle in relatively large populations.

PMID- 14652907
TI  - Birth weight and cognitive development in adolescence: causal relationship or
      social selection?
AB  - Using data from the National Longitudinal Survey of Adolescent Health (Add
      Health), I investigate the relationship between birth weight and cognitive
      development among adolescents aged 12-17. Initial OLS regression models reveal a
      significant, positive relationship between low birth weight and verbal ability.
      Controlling for demographic, socioeconomic, and other adolescent characteristics
      modifies, but does not eliminate, this relationship. Additional models that
      stratify the sample by parental education illustrate the greater importance of
      other family and adolescent characteristics for cognitive development in
      adolescence, and a diminished role of birth weight. In the final section of the
      paper, fixed effects models of non-twin full siblings indicate no significant
      association between birth weight and verbal ability, suggesting that traditional
      cross-sectional models overstate the influence of birth weight for cognitive
      development in adolescence.

PMID- 14652908
TI  - Social status and the secondary sex ratio: new evidence on a lingering
      controversy.
AB  - Because women are more likely than men to use social status as a criterion in
      mate selection, evolutionary theory has led to the hypothesis that higher
      proportions of males will be born to parents of high social status than to
      parents of low status. To date, the research that has tested this deduction has
      not provided consistent support. This could be partly due to the small sample
      size in several of the studies. The present study tested the hypothesis using 6
      different social status measures provided by more than 11,000 United States and
      Canadian college students. The offspring sex ratio was measured by asking the
      students their own sex plus that of each of their siblings. No evidence was found
      to support the hypothesis that parental social status has any significant effect
      on the sex ratio of offspring.

PMID- 14652909
TI  - The effects of infant deaths on the risk of subsequent birth: a comparative
      analysis of DHS data from Ghana and Kenya.
AB  - This paper examines the conditions under which there might be a strong or weak
      relationship between childhood mortality and fertility at the micro level. The
      premise is that as a society undergoes transition during which a conscious effort
      is made to space and limit birth, the effect associated with infant death on the
      risk of subsequent birth reduces. Using the 1998 DHS data from Ghana and Kenya,
      our multivariate hazard models show that women who have experienced infant deaths
      tend to have a higher risk of subsequent births than those without any infant
      deaths at all parities studied in both countries. In a comparative context,
      however, the magnitude of the effect associated with infant death was weaker in
      Kenya at all parities, corroborating the hypothesis that the effect indeed
      reduces in the course of transition. Besides infant deaths, other demographic,
      socioeconomic and sociocultural factors were also found to associate with the
      risk of births. The limitations and policy implications of the findings are
      discussed.

PMID- 14652910
TI  - Declining fertility among North American Hutterites: the use of birth control
      within a Dariusleut colony.
AB  - Historically, population researchers considered the Hutterites the champions of
      high fertility, since they most closely approximated the human fertility
      potential. Yet contemporary researchers have found evidence of a decline in
      fertility and a shift from natural to controlled fertility behavior among the
      Hutterite population. Various reasons for these recent changes have been
      suggested, including the use of birth control. Using interview data from a
      Dariusleut colony, this is the first paper to document the presence and
      prevalence of birth control among the North American Hutterites. All interviewed
      women recognized the use of birth control and reported that female sterilization
      was the most commonly used method. I address how the various forms of birth
      control and the reasons for its use relate to the Hutterite ideology.

PMID- 14652911
TI  - Polygyny and child survival in West Africa.
AB  - This study examines the relationship between polygyny and child survival in light
      of conflicting findings reported in a number of studies. Using data from the
      Demographic and Health Surveys from six West African countries, the risks of
      neonatal, postneonatal, and overall infant mortality are estimated. Controlling
      for a set of social and bio-demographic factors, it is found that substantial
      risks of mortality are associated with polygyny. A separate analysis explores the
      possibility that polygyny's impact could differ from country to country. No
      significant interaction effects are detected, leading to the conclusion that
      regardless of the country in which it is practiced, polygyny still poses a
      challenge to the survival chances of West African children.

PMID- 14652912
TI  - A research note on body mass, physical aggression, and the competitiveness of
      Asian-Pacific Islander adolescents in Guam.
AB  - This study uses the evolutionary model to guide an exploration of the effects of
      body mass on aggressive and competitive behaviors among Asian-Pacific adolescents
      in Guam. Using a probability sample of Guam's high-school students, the results
      of logistic regressions suggest that adolescent females with greater body mass
      are more likely to engage in physical fights (aggression) and to participate in
      team sports (competitiveness). Ethnic differences indicate the possibility that
      individuals with lower body mass may be less likely to participate in physically
      aggressive acts and team sports. Alternate theoretical explanations for the
      results are also considered.

PMID- 14652913
TI  - Social and biological measures of hyperactivity and inattention: are they
      describing similar underlying constructs of child behavior?
AB  - The relationship between 27 different measures of hyperactive, impulsive, and
      inattentive behavior, including those considered to be more objective and those
      considered more influenced by social factors, is examined using a normal sample
      of 219 Mexican children, ages 6 to 12. Measures were based on activity monitoring
      by accelerometry, ethological observation of attentional and movements states in
      the classroom, cognitive testing using the TOVA continuous performance test
      (CPT), and parents' and teachers' reports on ratings scales and symptom
      checklists. Factor analysis was used to examine to what degree these different
      measures are reporting similar underlying constructs (factors) of hyperactivity
      and inattention. Parent and teacher ratings appear to be describing underlying
      constructs that are distinct from those described by the other measures, but
      measures based on CPT, observation, and activity monitoring did not factor
      together either, nor more highly correlate to each other. Analysis combining all
      the measures showed that parent and teacher ratings factored together based on
      who was reporting the behavior, rather than the behavior being reported. The
      findings underscore that each type of measurement of hyperactivity, impulsivity,
      and inattention measures a different aspect of a complex behavioral phenomenon,
      rather than some better measuring than others the same underlying factor.

PMID- 14652914
TI  - The effect of the nurturant bonding system on child security of attachment and
      dependency.
AB  - This paper uses a biopsychosocial theory of human bonding to explore the
      intergenerational transmission of bonding traits. More specifically, it examines
      how the nurturant bonding system of the mother affects the succorant bonding
      system of the young child. In the first section of the paper, we take the bonding
      framework proposed by Miller and Rodgers (2001) and elaborate its implications
      for mother-child dyads. Next, we describe the collection of data from 78 mothers
      prior to their pregnancy with an index child and again when that child is between
      the ages of two and four and a half. These data allow the creation of a number of
      mother and child variables that are derived from the bonding framework. Using
      these variables, we construct a temporally organized, structural equation model
      of maternal effects on the child, with the two main outcome variables being child
      security of attachment and child dependency. We then test the model using LISREL.
      Although the results are tentative and require further confirmatory research,
      they lend support to three broad hypotheses derived from the bonding framework.
      In particular, the results support the construct of a motivational substrate that
      affects both maternal childbearing and her child-rearing behaviors. They also
      indicate the importance of child temperament in the formation of the succorant
      bond. Finally, they demonstrate that the preconception nurturant characteristics
      of the mother have multiple effects on the two main outcome variables, child
      security of attachment and dependency. Two submodels based on predictors of these
      two outcomes reveal a number of pathways along which these effects take place. We
      conclude with a brief discussion of the lessons learned that might strengthen
      future studies of mother-child bonding and, more generally, the intergenerational
      transmission of bonding traits.

PMID- 14652915
TI  - Genealogical data and the biodemography of human longevity.
AB  - Biodemography of human longevity is an emerging interdisciplinary field of
      sociobiological research with deep historical roots. Two research questions are
      examined in this article: (1) What evidence is there for the familial
      transmission of human longevity?, and (2) what are the effects of parental age at
      reproduction on offspring longevity, and in particular, are there long-term
      adverse health consequences associated with the trend toward delayed
      reproduction? The ability of scientists to conduct biodemographic studies depends
      not only on merging theoretical and methodological elements from the biological
      and demographic/actuarial sciences, but unique sources of data and statistical
      methods must also be developed. In this article we describe how gencalogical data
      have been used for over a century to explore basic questions about human
      longevity, and how similar kinds of data now being developed are driving the
      formation of new testable research hypotheses in the field of biodemography.

PMID- 14652916
TI  - Parents' age at birth of their offspring and child survival.
AB  - This study presents some new results on parental age as a risk factor for child
      survival. The study is based on individual registration forms for live births and
      infant deaths collected in Hungary from 1984 to 1988. Logistic regression models
      have been fitted for early neonatal and neonatal mortality on the one hand, and
      post-neonatal mortality on the other hand. Children of older males and females
      have significantly higher early neonatal and neonatal mortality rates compared to
      those of younger males and females. The impact of age of both parents remains,
      however, slighter than that of other biological characteristics such as previous
      number of fetal deaths, induced abortions, or live births. The authors discuss
      possible biological explanations.

PMID- 14652917
TI  - Fertility and post-reproductive longevity.
AB  - We examine the effects of reproduction on longevity among mothers and fathers
      after age 60. This study is motivated by evolutionary theories of aging and
      theories predicting social benefits and costs of children to older parents. We
      use the Utah Population Database, that includes a large genealogical database
      from the Utah Family History Library. Cox proportional hazard models based on
      13,987 couples married between 1860-1899 indicate that women with fewer children
      as well as those bearing children late in life live longer post-reproductive
      lives. As the burdens of motherhood increase, the relative gains in longevity of
      late fertile women increase compared to their non-late fertile counterparts.
      Husbands' longevity is less sensitive to reproductive history, although husbands
      have effects that are similar to those of their wives during the latter marriage
      cohort. We find some support for predictions based on evolutionary principles,
      but we also find evidence that implicates a role for shared marital environments.

PMID- 14652918
TI  - Individual aging and mortality rate: how are they related?
AB  - Many researchers working in the area of aging and longevity base their
      conclusions on the behavior of empirical age trajectories of mortality rates. In
      such analyses, changes in the slope of the logarithm of the mortality curve are
      often associated with changes in the rate of individual aging. We show that such
      interpretation may be incorrect: the changes in the slope of this curve do not
      necessarily correspond to the changes in the rate of individual aging. We use
      three models of mortality and aging to illustrate this statement. The first one
      is based on the idea of frailty. We show that changes in frailty distribution
      alone may be responsible for changes in the slope. The second model exploits the
      idea of saving lives. It evaluates changes in mortality rate after elimination of
      lethal stressful events. The third model uses the idea of Strehler and Mildvan
      (1960). It shows that changes in the rate of individual aging may take place
      without changes in the slope of the logarithm of the mortality curve.

PMID- 14652920
TI  - [Human metapneumonia virus and West Nile virus].

PMID- 14652919
TI  - Between nurture and nature: the shifting determinants of female fertility in
      Danish twin cohorts.
AB  - Behaviors related to fertility constitute primary candidates for investigating
      the relevance of evolutionary influences and biological dispositions on
      contemporary human behaviors. Using female Danish twin cohorts born 1870-1968, we
      document important transformations in the relative contributions of "nurture" and
      "nature" to within-cohort variations in early and complete fertility, and we
      point toward a systematic relation between the socioeconomic context of cohorts
      and the relevance of genetic and shared environmental factors. This
      transformation is most striking for early fertility where genetic factors
      strengthen over time and are consistent with up to 50 percent of the variation in
      early fertility in most recent cohorts. Understanding this emerging relevance of
      genetic factors is of central importance because early fertility constitutes an
      important determinant of complete fertility levels in low-fertility societies,
      and because teenage motherhood and early childbearing are often associated with
      negative life-cycle consequences. Moreover, our results emphasize the need for
      socially and contextually informed analyses of nature and nurture that allow both
      factors to influence human reproductive behavior over time.

PMID- 14652921
TI  - [Lipid metabolism diseases].

PMID- 14652922
TI  - [Acetylcysteine in chronic obstructive pulmonary disease. Secretolytic,
      antioxidant or placebo?].

PMID- 14652923
TI  - [Neural transplantation for restoration of nerve function. Physiological basis
      and clinical results].

PMID- 14652924
TI  - [Diclofenac caused renal insufficiency. A case illustrating the necessity of
      pharmaceutical intervention and care].

PMID- 14652925
TI  - [Cold and colds?].

PMID- 14652926
TI  - [Pharmacologic effect of foods of plant origin. "Functional food" fresh from the
      market].

PMID- 14652927
TI  - [Testing of secondary plant products. Juicing good for the immune system?].

PMID- 14652928
TI  - [A diet for preventing colorectal cancer?].

PMID- 14652929
TI  - [Life style illness arteriosclerosis. Antioxidants at the heart of the issue].

PMID- 14652930
TI  - [Colleague references on chronic diarrhea: an array of diagnoses (interview by
      Dr. med. Thomas Meissner)].

PMID- 14652931
TI  - [With considerable finesse toward smoother, more beautiful, young.... Methods of
      dermatologists who treat below the skin].

PMID- 14652932
TI  - [New irradiation method in breast cancer. What is the value of brachytherapy?
      (interview by Erik Heintz)].

PMID- 14652933
TI  - [Shockwaves in plantar fasciitis without effect. Apparently a "hard" indication
      qualfies].

PMID- 14652934
TI  - [Why are results of studies with digitalis so poor? "It depends on potassium!"].

PMID- 14652935
TI  - [Therapy after tick bite. Please give exact dosage and time].

PMID- 14652936
TI  - [Infections with boomerang effect. How do you protect your patients from
      recurrences?].

PMID- 14652937
TI  - [Chronic recurrent otitis externa. Excessive ear hygienic care can have
      sequelae].
AB  - Numerous factors may be involved in the development of chronic recurrent otitis
      externa: altered pH of the cerumen, increased susceptibility to contact allergens
      (e.g. nickel ear-rings) in atopic patients, the use of instruments for cleaning
      out the auditory canal, the presence of a foreign body, congential narowing of
      the auditory canal, or systemic diseases (in particular diabetes mellitus). For
      diagnostic purposes, the use of the otoscope is mandatory, and swabs to determine
      the presence of bacteria or fungi are to be recommended. Treatment is dictated by
      the clinical picture presenting, and may comprise the local application of
      antibiotic cortisone containing or antimycotic preparations and temponade of the
      auditory canal (acute inflammatory phase) or pH-stabilizing lotions (chronic dry
      inflammatory phase) with the aim of ameliorating the frequently highly
      troublesome pruritus.

PMID- 14652938
TI  - [Recurrent urinary tract infections should not be treated cavalierly. First
      verify the diagnosis!].
AB  - Acute uncomplicated cystitis (AUC) and acute uncomplicated pyelonephritis (AUP)
      are two common urinary tract infections (UTI) in otherwise healthy young women.
      Both weaknesses of the mucosal barrier and specific factors of uropathogenic
      bacteria  must be present before the bacteria can adhere to the urothelium and
      give rise to an infection. These circumstances are also of relevance in recurrent
      UTI.  Antibiotic treatment of AUC and AUP is based  on the guidelines of the
      Infectious Diseases Society of America (IDSA). For the prevention of recurrent
      UTI, antibiotics, functional foods, injections, probiotic agents and other
      measures are recommended with varying potential for success.

PMID- 14652939
TI  - [Recurrent infections of female genitalia. Weak immunity or wrong therapy?].

PMID- 14652940
TI  - [Hematemesis in the child. Determining the etiology].

PMID- 14652941
TI  - [Self-medication with nicotine preparations. 3 of 10 smokers renounce the blue
      fumes].

PMID- 14652942
TI  - [Vaccinate against influenza and other pathogens. With or without consultation
      fee?].

PMID- 14652943
TI  - [Up to 15,000 fatalities in the last season. Arm your patients now for the next
      influenza epidemic!].

PMID- 14652944
TI  - [Acute coronary syndrome--but no coronary stenoses!].

PMID- 14652945
TI  - [The red eye].

PMID- 14652946
TI  - Hero turned villain--Mugabe's health system is in shambles.

PMID- 14652947
TI  - Dispensing doctors disadvantaged by pharmacy clinics and new law on dispensing.

PMID- 14652948
TI  - Extrauterine pregnancy.

PMID- 14652949
TI  - Economy class syndrome.

PMID- 14652950
TI  - National health insurance--friend or foe?

PMID- 14652951
TI  - Toy gun injuries.

PMID- 14652952
TI  - Guidelines for CPD accreditation of the South African Society of Medical
      Oncology.

PMID- 14652953
TI  - Regional analgesia abseils into the limelight.

PMID- 14652954
TI  - Inborn errors of metabolism: heartache-saving test to go national.

PMID- 14652955
TI  - Health carers cracking under HIV/AIDS workload.

PMID- 14652956
TI  - Telemedicine boost for Matie campus.

PMID- 14652957
TI  - A case of national child neglect?

PMID- 14652958
TI  - Aspen manufactures Africa's first generic ARVs.

PMID- 14652959
TI  - Revolutionary HIV/AIDS-management pilot for Eastern Cape.

PMID- 14652960
TI  - World Bank warning: AIDS to cause complete economic collapse within 3
      generations.

PMID- 14652961
TI  - Specialised outsourcing of managed care takes a bow.

PMID- 14652962
TI  - Protecting the public, guiding the professions.

PMID- 14652963
TI  - New anabolic agents in the treatment of osteoporosis.

PMID- 14652964
TI  - Intrauterine growth and disease in later life--Barker and beyond.

PMID- 14652965
TI  - Etorphine poisoning.

PMID- 14652967
TI  - Puzzles in the causation and epidemiology of prostate cancer--a sombre outlook.

PMID- 14652966
TI  - Strengthening the health system and ensuring equity in the widescale
      implementation of an antiretroviral therapy programme in South Africa.

PMID- 14652968
TI  - Medical aid schemes, HIV status and 'material non-disclosure'.

PMID- 14652969
TI  - Cervical pregnancy in an HIV-infected patient treated by uterine artery
      embolisation and methotrexate.

PMID- 14652970
TI  - Changes in the patient population attending a primary health care clinic in rural
      South Africa between 1991 and 2001.

PMID- 14652971
TI  - The prevention of mother-to-child HIV transmission programme and infant feeding
      practices.
AB  - Since the first cases of HIV transmission through breast-feeding were documented,
      a fierce debate has raged on appropriate guidelines for infant feeding in
      resource-poor settings. A major problem is determining when it is safe and
      feasible to formula-feed, as breast-milk protects against other diseases. A cross
      sectional survey of 113 women attending the programme for the prevention of
      mother-to-child transmission in Khayelitsha, Cape Town, was conducted. Over 95%
      of women on the programme formula-fed their infants and did not breast-feed at
      all. Seventy per cent of women said that their infant had never had diarrhoea,
      and only 3% of children had had two episodes of diarrhoea. Focus groups
      identified the main reasons for not breast-feeding given by women to their
      families and those around them. Formula feeding is safe and feasible in an urban
      environment where sufficient potable water is available.

PMID- 14652972
TI  - Percutaneous endoscopic gastrostomy in children--a 5-year experience.
AB  - INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) has been performed on
      children since 1979. The indications for a PEG are wide ranging and while there
      are well-established benefits, it remains a procedure with recognised
      complications. GOALS AND OBJECTIVES: The goal of this study was to review our
      experience with this procedure at a South African paediatric tertiary referral
      hospital over a 5-year period. The objectives were to review PEGs with regard to
      patient characteristics, indications, anaesthesia time required and
      complications. METHODS: The study was a retrospective case record review.
      RESULTS: A total of 70 PEGs were performed. Patients had a mean age of 4 years
      and 3 months, and a mean weight of 12.2 kg at the time of performing the
      procedure. The mean anaesthetic time required for performing a PEG was 27
      minutes. Fifty-four PEGs (77%) were performed for inability to swallow, 15 (21%)
      to improve caloric intake, and 1 (1%) for continuous enteral feeding. There were
      no deaths, 5 patients had major complications (6%), and 12 patients (17%) needed
      antireflux surgery subsequent to the placement of a PEG. DISCUSSION: There is an
      increasing demand for PEGs at our institution. The indications for a PEG in this
      series are similar to those reported in other series, although we may be
      underutilising PEGs to improve caloric intake. Our complication rates compare
      favourably with those reported in other series. We have, however, identified post
      PEG gastrooesophageal reflux disease as a complication we would like to reduce,
      and suggest a practical approach to do so.

PMID- 14652973
TI  - Bimodal distribution of fasting gastric acidity in a rural African population.
AB  - SETTING: The people of Transkei eat a diet high in linoleic acid, the principal
      fatty acid in maize. The theory has been put forward that a diet high in linoleic
      acid and low in fat and riboflavin, such as the traditional diet in Transkei,
      results in overproduction of prostaglandin E2 in the gastric mucosa, and that
      this overproduction in turn causes a suppression of gastric acid production.
      OBJECTIVE: To investigate the effect of diet on fasting gastric pH in a rural
      black African population. DESIGN: Fasting gastric acid samples were obtained by
      fine nasogastric tube aspiration from 150 volunteers at a rural health clinic.
      The pH of these samples was measured and a full dietary questionnaire was used.
      Helicobacter pylori serology was done on a subgroup of 30 volunteers. RESULTS AND
      CONCLUSIONS: A bimodal pH distribution was found. Approximately half the
      population had a gastric pH within the range 1-4. Half had a pH of over 4. A high
      pH was significantly associated with consumption of maize (p = 0.006), and with
      consumption of both pumpkin and beans (p = 0.006). A high proportion of this
      rural African population has a diet-associated abnormally high gastric pH. The
      pattern of upper gastrointestinal disease may be significantly affected by diet
      in this community and in others with a similar diet.

PMID- 14652974
TI  - Do South African medical students of rural origin return to rural practice?
AB  - OBJECTIVES: To investigate the career choices of medical graduates of rural
      origin in the South African context, and to determine what proportion of rural
      origin graduates are currently practising in a rural area. DESIGN: This is a
      retrospective descriptive study. Doctors' addresses at the time of graduation
      were compared with their current addresses in terms of rural/urban
      classification, and a questionnaire survey was done. SUBJECTS: Sample A consisted
      of a cohort of doctors who graduated in 1991 and 1992. Sample B consisted of the
      1994-1996 graduates of two medical schools. OUTCOME MEASURES: Percentage of rural
      origin graduates in rural practice. RESULTS: In sample A 14.4% were rural-origin
      students. When comparing addresses, it was found that 38.4% of rural-origin
      graduates are currently practising in rural areas, compared with 12.4% of urban
      origin graduates (p < 0.001). The questionnaire data showed that 45.9% of the
      rural-origin respondents are in rural practice, compared with 13.3% of the urban
      origin respondents (p = 0.001). In sample B, 41.61% of the rural-origin graduates
      are in rural practice compared with 5.08% of urban-origin graduates (p < 0.001).
      CONCLUSION AND RECOMMENDATIONS: The findings suggest that the South African
      situation is similar to that in other countries, with rural-origin medical
      students more likely to choose rural careers than urban-origin students. Rural
      origin graduates are also more likely to choose general practice. It is
      recommended that the selection criteria of the medical faculties be reviewed with
      regard to rural origin, and that the career aspirations of applicants to medical
      school be taken into account in selection, particularly with regard to primary
      care or general practice.

PMID- 14652976
TI  - Pharmacists mull transmission risks of FluMist.

PMID- 14652977
TI  - International pharmacists group convenes in Australia. FIP adopts policies on
      counterfeit medications, adherence to long-term therapies.

PMID- 14652975
TI  - Haemophilia patients aged 0-18 years in the Western Cape.
AB  - OBJECTIVES: To record the number of haemophilicas aged 0-18 years in the Western
      Cape (WC), what event led to the diagnosis, the level of clotting factor,
      treatment, functional status of their joints and impact of the disease on the
      family. DESIGN: A prospective study of patients registered with the South African
      National Haemophilia Registry and new patients, utilising the patients'
      paediatricians, hospital records, patient and guardian interviews, physical
      examination and provincial nurse haemophilia co-ordinators. SETTING: Haemophilia
      care centres at the three WC academic hospitals, regional hospitals and homes of
      patients. Two elective medical students, MHH and JJH, collected the information.
      SUBJECTS: All boys with confirmed haemophilia A or B in the WC. OUTCOME MEASURES:
      Events that led to diagnosis, degree of haemophilia, use of clotting factor,
      functional status, and effect on family. RESULTS: Of 78 patients (59 haemophilia
      A, 19 haemophilia B) identified, 49 could be studied. Forty-three per cent had
      severe, 29% moderate and 22% mild disease (6% unknown). Family history was
      present in 49%, but led to diagnosis in only 12%. The most common first symptoms
      were subcutaneous and mucosal bleeding. Delay in diagnosis varied from 0 to 9
      months. Twenty-nine per cent of guardians were suspected of child abuse. RSA
      produced clotting factor was used 'on demand' in 73% of patients, for periodic
      prophylaxis in 20% and as continuous prophylaxis in 7%. Joints were functionally
      restricted in 43% of patients. The majority of guardians (59%) said the disease
      had a major impact on the family. CONCLUSIONS: The diagnosis of haemophilia in
      children with a positive family history was often delayed. Haemophilia causes
      significant morbidity in our patients and their families.

PMID- 14652978
TI  - How nurse practitioners obtained provider status: lessons for pharmacists.
AB  - The history of nurse practitioners, their efforts to achieve provider status, and
      lessons learned from their activism are discussed. The nurse practitioner
      profession arose out of a need to meet a rising demand for primary care services,
      especially in rural areas. Some nurses and physicians vehemently opposed the
      nurse practitioner model, but studies documented the value of nurse practitioner
      services, and the utilization of these practitioners continued to grow.
      Compensation was provided via salary or per-member-per-month agreements. Nurse
      practitioners recognized that direct federal reimbursement (provider status) was
      needed to recognize them as independent health care providers and assign specific
      monetary values to their services, so they undertook an aggressive lobbying
      campaign. Contacts on Capitol Hill were exploited, and nursing organizations
      encouraged nurse practitioners to get involved in grass-roots activism. Nurse
      practitioners discussed their patients during meetings with their representatives
      in Congress, and legislators were invited to make site visits. In 1993, the
      American College of Nurse Practitioners was formed to unite the profession and
      move the campaign forward. Ultimately, the Balanced Budget Act of 1997 granted
      nurse practitioners provider status and authorized them to bill Medicare directly
      for services furnished in any setting. The key strategies that contributed to
      this victory were (1) gaining recognition that nursing had the potential to
      expand its role, (2) documenting nurse practitioners' value, (3) establishing
      standards in education and credentialing, (4) using professional organizations to
      empower individuals, and (5) being willing to accept small, incremental gains
      over time. The experience of nurse practitioners in obtaining Medicare provider
      status offers valuable lessons for pharmacists as they pursue the same goal.

PMID- 14652979
TI  - Impact of prophylactic i.v. magnesium on the efficacy of ibutilide for conversion
      of atrial fibrillation or flutter.
AB  - The impact of prophylactic i.v. magnesium on the efficacy of ibutilide for
      conversion of atrial fibrillation and flutter to normal sinus rhythm was studied.
      In this multicenter cohort study, all patients in three large, tertiary care
      centers who received ibutilide for acute chemical conversion of atrial
      fibrillation or flutter from August 1996 through December 2001 were identified
      through pharmacy or billing records. Patients who did not receive magnesium
      before or during ibutilide therapy served as the control group, while those who
      received magnesium less than two hours before or during ibutilide administration
      served as the study group. The rate of administration of direct-current
      cardioversion (DCC) and the occurrence of ventricular arrhythmia were compared
      between those who did and did not receive magnesium. The rates of successful
      cardioversion were also assessed. Categorical data were analyzed using chi-square
      analysis or Fisher's exact test. Demographic data were analyzed using Student's t
      test. The medical records of 321 patients were analyzed. Successful chemical
      cardioversion in the study group was approximately 19% higher than in those who
      did not receive magnesium (p = 0.040). The use of DCC in the group who received
      magnesium was reduced by approximately 34% (p = 0.045). The conversion rate of
      atrial fibrillation or flutter with ibutilide was enhanced by magnesium
      administration (p = 0.040), and the rate of administration of DCC was reduced (p
      = 0.045) in patients who received magnesium. There was a nonsignificant reduction
      in the occurrence of ventricular arrhythmias (p = 0.533). The efficacy of
      ibutilide was enhanced by concomitant administration with intravenous magnesium.

PMID- 14652980
TI  - Using a closed-system protective device to reduce personnel exposure to
      antineoplastic agents.
AB  - Surface contamination with and personnel exposure to antineoplastic agents before
      and after the implementation of a closed-system protective device were studied.
      Samples were collected before and six months after implementation of PhaSeal, a
      closed-system device for limiting exposure to antineoplastic agents during
      preparation and administration. Personnel exposure was evaluated by collecting 24
      hour urine samples from pharmacists, pharmacy technicians, and nurses working
      full-time in a chemotherapy drug infusion center and pharmacy. Surface
      contamination was assessed by wiping potentially exposed surfaces. Both types of
      samples were analyzed for cyclophosphamide and ifosfamide by high-performance
      liquid chromatography-electrospray ionization-tandem mass spectrometry. All 17
      wipe samples collected before implementation of PhaSeal had detectable levels of
      cyclophosphamide, and 11 were positive for ifosfamide. Six months after system
      implementation, 7 of 21 wipe samples had detectable levels of cyclophosphamide
      and 15 were positive for ifosfamide. Of eight employees who provided urine
      samples, six were positive for cyclophosphamide and two for ifosfamide before
      implementation, and none were positive for either drug after implementation. The
      PhaSeal system appeared to reduce exposure of health care personnel to
      cyclophosphamide and ifosfamide.

PMID- 14652981
TI  - Cost analysis of continuous versus intermittent infusion of piperacillin
      tazobactam: a time-motion study.
AB  - The time and associated costs (drug, labor, supply) of administering a continuous
      versus an intermittent i.v. infusion of piperacillin-tazobactam were compared.
      The total labor cost was calculated for each regimen based on the time required
      for nurses, pharmacists, and pharmacy technicians to either prepare or administer
      the drug, according to their standard responsibilities. Thirty timed observations
      were made for each of the dosing formulations. Observations were conducted on
      separate occasions for at least four different nurses, pharmacists, and pharmacy
      technicians per formulation. Labor costs were calculated by multiplying the mean
      times recorded by the average U.S. hourly wages and local wages for these health
      professionals and extrapolated to encompass a 24-hour period of drug
      administration. The average wholesale price and hospital contract price of
      piperacillin-tazobactam were used to calculate the costs of both intermittent and
      continuous infusions. The costs for all items used in drug preparation and
      administration were also calculated for supplies. Basic descriptive statistics
      were used to evaluate the costs of the time needed to prepare and administer the
      different regimens. Drug acquisition costs accounted for the largest percentage
      of the total cost for all regimens. Analysis of labor costs revealed that nursing
      time accounted for the majority of the labor costs, with continuous infusion
      regimens being the least time-consuming and least costly administration method.
      Continuous-infusion regimens were more cost-efficient when evaluated on a daily
      basis and for the total cost of 5- and 10-day treatments. The use of continuous
      infusion as a means of administering piperacillin-tazobactam maximized the drug's
      pharmacodynamics and was more cost-efficient than intermittent infusion of the
      drug.

PMID- 14652982
TI  - Meeting the modified drug information requirements of ASHP-accredited pharmacy
      practice residency programs.
AB  - The current standards for meeting drug information (DI) requirements in American
      Society of Health-System Pharmacists (ASHP)-accredited pharmacy practice
      residency (PPR) programs and the impact of changes in ASHP standards for the DI
      requirements were studied. In September 2002 a nine-question survey was e-mailed
      to the directors of all ASHP-accredited PPR programs listed with an available e
      mail address on ASHP's residency directory Web page as of August 2002. The
      program directors were asked to provide information on the demographics of their
      practice settings, the current methods of completing the DI requirements of their
      programs, whether the DI requirements had changed between the 2001-02 and 2002-03
      residency years, and whether any changes in the DI requirements were anticipated.
      A total of 178 (49%) of 365 PPR programs responded. Of the respondents, 87% were
      located in a hospital setting, 33% were affiliated with a school of pharmacy, and
      40% had a formal onsite DI center. Half of the respondents fulfilled DI
      requirements through a longitudinal rotation, 20% through a block rotation, and
      27% through both. Eighty-two percent of the respondents were familiar with the
      revised ASHP DI requirements, and 26% had modified their DI requirements between
      the 2001-02 and 2002-03 residency years. Seventeen percent anticipated changing
      their DI requirements in the future. Influences for modifications to the
      programs' DI requirements were mainly ASHP revisions and feedback from preceptors
      and residents. A national survey suggested that DI requirements in PPR programs
      are primarily achieved through a longitudinal rotation design.

PMID- 14652983
TI  - Use of a PDA-based pharmacist intervention system.

PMID- 14652984
TI  - Availability of antidotes in Quebec hospitals before and after dissemination of
      guidelines.

PMID- 14652985
TI  - Pharmaceutical care model for elderly patients in South Carolina.

PMID- 14652986
TI  - Triple antifungal therapy for the treatment of invasive aspergillosis in a
      neutropenic pediatric patient.

PMID- 14652987
TI  - ASHP therapeutic position statement on strict glycemic control in patients with
      diabetes.
AB  - The deleterious effects of hyperglycemia have been documented from the
      biochemical to the pathophysiologic level. Given the research findings and the
      guidelines for glycemic control established by ADA and ACE, ASHP supports and
      encourages strict glycemic control in all appropriate patients with diabetes
      mellitus to reduce the progression of chronic complications.

PMID- 14652988
TI  - A pharmacist's reflections on Calvino's Six memos.

PMID- 14652989
TI  - Proton-pump inhibitors in a Navy hospital after a formulary change.

PMID- 14652990
TI  - Patient-safety mandates in ambulatory care.

PMID- 14652991
TI  - Computers can foil insurance recoveries.

PMID- 14652992
TI  - Turning Medicare billings into revenue.

PMID- 14652993
TI  - Aligned nanotubes.
AB  - Since the discovery of carbon nanotubes by lijima in 1991, various carbon
      nanotubes with either a single- or multilayered graphene cylinder(s) have been
      produced, along with their noncarbon counterparts (for example, inorganic and
      polymer nanotubes). These nanostructured materials often possess size-dependent
      properties and show new phenomena related to the nanosize confinement of the
      charge carriers inside, which leads to the possibility of developing new
      materials with useful properties and advanced devices with desirable features for
      a wide range of applications. In particular, carbon nanotubes have been shown to
      exhibit superior properties attractive for various potential applications,
      ranging from their use as novel electron emitters in flat-panel displays to
      electrodes in electrochemical sensors. For many of the applications, it is highly
      desirable to have aligned/patterned forms of carbon nanotubes so that their
      structure/property can be easily assessed and so that they can be effectively
      incorporated into devices. In this Review, we present an overview on the
      development of aligned and micropatterned nanotubes, with an emphasis on carbon
      nanotubes.

PMID- 14652995
TI  - QM/MM Car-Parrinello molecular dynamics study of the solvent effects on the
      ground state and on the first excited singlet state of acetone in water.
AB  - We present a hybrid Car-Parrinello quantum mechanical/molecular mechanical
      (QM/MM) approach that is capable of treating the dynamics of molecular systems in
      electronically excited states in complex environments. The potential energy
      surface in the excited state is described either within the restricted open-shell
      Kohn-Sham (ROKS) formalism or within time-dependent density functional theory
      (TDDFT). As a test case, we apply this technique to the study of the solvent
      effects on the ground state and on the first excited singlet state of acetone in
      water. Our results demonstrate that for this system a purely classical
      description of the solvent is sufficient, since inclusion of the first solvent
      shell of 12 water molecules into the quantum system does not show a significant
      effect on this transition. The excited-state energies calculated with ROKS are
      red shifted by a constant value compared to the TDDFT results, while the relative
      variations of the excitation energy for different configurations are in very good
      agreement. The experimentally observed blue shift of the excitation energy in
      going from gas phase to condensed phase is well reproduced. Excited-state
      dynamics carried out with ROKS yield the relaxation of the solute and the
      rearrangement of the solvent structure on a picosecond timescale. The calculated
      Stokes shift is in reasonable agreement with experimental data.

PMID- 14652994
TI  - Nanotubes a la carte: wetting of porous templates.
AB  - Nanotubes have an outstanding potential both for applications in nanotechnology
      and as the subject of basic research. Wetting of porous templates is a simple
      technique that overcomes many limitations of established preparation methods. It
      extends the range of processable materials, for example, by a broad range of
      multicomponent mixtures or by high-performance polymers such as poly(oxy-1,4
      phenyleneoxy-1,4-phenylenecarbonyl-1,4-phenylene) (PEEK) and
      polytetrafluoroethylene (PTFE). Inducing controlled phase transitions generates a
      large specific surface, a specific nanoporosity, or oriented crystalline domains
      within the nanotube walls. Template wetting provides customized nanotubes and
      allows us to investigate how the wall curvature affects the structure formation.

PMID- 14652996
TI  - Topological and electron-transfer properties of yeast cytochrome c adsorbed on
      bare gold electrodes.
AB  - The redox metalloprotein yeast cytochrome c was directly self-chemisorbed on
      "bare" gold electrodes through the free sulfur-containing group Cys102.
      Topological, spectroscopic, and electron transfer properties of the immobilised
      molecules were investigated by in situ scanning probe microscopy and cyclic
      voltammetry. Atomic force and scanning tunnelling microscopy revealed individual
      protein molecules adsorbed on the gold substrate, with no evidence of aggregates.
      The adsorbed proteins appear to be firmly bound to gold and display dimensions in
      good agreement with crystallographic data. Cyclic voltammetric analysis showed
      that up to 84% of the electrode surface is functionalised with electroactive
      proteins whose measured redox midpoint potential is in good agreement with the
      formal potential. Our results clearly indicate that this variant of cytochrome c
      is adsorbed on bare gold electrodes with preservation of morphological properties
      and redox functionality.

PMID- 14652997
TI  - A combined atomic force microscopy and molecular dynamics simulation study on a
      plastocyanin mutant chemisorbed on a gold surface.
AB  - A mutant of copper plastocyanin, covalently bound to an Au (111) surface through
      an engineered disulfide bridge, was investigated in aqueous medium by atomic
      force microscopy (AFM) and molecular dynamics (MD) simulations. Tapping-mode AFM
      images revealed adsorption of single molecules which are homogeneously
      distributed over the substrate and strongly bound to gold and display uniform
      lateral size. A statistical analysis of the height of the macromolecules on the
      gold substrate evidenced a distribution around a mean value consistent with that
      expected from the crystallographic data and with a relatively large standard
      deviation. A 10-ns classical MD simulation of mutated plastocyanin, hydrated by a
      layer of water, covalently bound to a gold surface by one or two sulfur atoms,
      was performed. The simulations indicate that the bound protein retains, in both
      cases, its overall tertiary structure during the dynamic evolution. Moreover, the
      macro-molecule can assume different orientations with respect to the gold
      substrate, which give rise to a distribution of heights on the gold substrate.
      Experimental and MD simulation results are compared and discussed in connection
      with the topological and dynamical properties of the protein system.

PMID- 14652998
TI  - A high-speed atomic force microscope for studying biological macromolecules in
      action.
AB  - The atomic force microscope (AFM), which was invented by Binnig et al. in 1986,
      can image at nanometer resolution individual biological macromolecules on a
      substrate in solution. This unique capability awoke an expectation of imaging
      processes occurring in biological macromolecules at work. However, this
      expectation was not met, because the imaging rate with available AFMs was too low
      to capture biological processes. This expectation has at last been realized by
      the high-speed AFM developed by our research group at Kanazawa University. In
      this article, after a brief review of the development of our apparatus, its
      recent advancement and imaging data obtained with motor proteins are presented.

PMID- 14652999
TI  - Magneto-optical studies of HgTe/HgxCd1-xTe(S) core-shell nanocrystals.
AB  - The synthesis and magneto-optical properties of HgTe nanocrystals capped with
      HgxCd1-xTe(S) alloyed shells have been investigated. The magneto-optical
      measurements included the use of optically detected magnetic resonance (ODMR) and
      circular polarized photoluminescence (CP-PL) spectroscopy. The PL spectra suggest
      the existence of luminescence events from both the core HgTe and the HgxCd1
      xTe(S) shells. The continuous-wave (cw) and time-resolved ODMR measurements
      revealed that the luminescence at the shell regime is associated with a trap-to
      band recombination emission. The electron trap is comprised of a Cd-Hg mixed
      site, confirming the existence of an alloyed HgxCd1-xTe(S) composition. The ODMR
      data and the CP-PL measurements together revealed the g-values of the trapped
      electron and the valence band hole.

PMID- 14653000
TI  - Electrochemical probing of photochemical reactions inside femtolitre droplets
      confined to electrodes.
AB  - Random ensembles of femtolitre-volume droplets containing redox active,
      photosensitive compounds immobilised on an electrode substrate permit
      photoelectrochemical studies within femtometric environments. Two chemical
      systems are described; the first is the N,N,N',N'-tetrahexyl-para
      phenylenediamine redox-catalysed photochemical debromination of the anaesthetic
      reagent halothane; the second is the photoinduced electron transfer from excited
      chlorophyll a to vitamin K1, which has possible potential in the development of
      solar cells based on photosynthesis.

PMID- 14653002
TI  - Optimal spectrum estimation in statistical mechanics.

PMID- 14653001
TI  - Radical ions from 3,3''',3''''-tris(butylsulfanyl)-
      2,2':5',2'':5'',2''',5''',2'''':5'''',2'''''-sexithiophene: an experimental and
      theoretical study of the p- and n-doped oligomer.
AB  - The 3,3''',3'''''-tris(butylsulfanyl)-
      2,2':5',2'':5'',2''',5''',2'''':5'''',2'''''-sexithiophene 1 was investigated
      through spectroscopic (NMR, EPR, UV/Vis-NIR), electrochemical,
      spectroelectrochemical and theoretical (DFT) studies. The charged species
      obtained upon its oxidation and reduction were characterised, showing that 1 can
      exist in at least five different oxidation states, that is, a neutral species, a
      radical cation, a dication, a radical anion, and a dianion. The long term
      stability of the radical cation 1+. was evidenced by the 1H NMR study in the
      presence of small quantities of trifluoroacetic acid (TFA). This approach allowed
      a comparison of the relative broadening of proton signals of 1, induced by the
      electron exchange process with traces of radical cation 1+., and the hfc
      (hyperfine coupling) constants obtained from the EPR study and DFT calculations.
      In the radical cation, all of the heterocyclic sulphur atoms are not
      significantly involved in the delocalisation of the unpaired electron, whereas
      the opposite holds for the radical anion. Time-dependent DFT calculations
      reproduced well the wavelengths of the optical transitions observed in the
      spectroelectrochemical experiments for all the five oxidation states and support
      the formation of the dianion 1(2-).

PMID- 14653003
TI  - Organization of water layers at hydrophilic interfaces.

PMID- 14653004
TI  - Additivity effects in the reactivities of bimetallic cluster ions PtmAun+.

PMID- 14653005
TI  - Electronic and geometrical structures of cyclopropanes: linear correlation of
      ionization energies with C-C bond lengths in monosubstituted cyclopropanes.

PMID- 14653006
TI  - Direct voltammetric evidence for a reducing agent generated from the
      electrochemical oxidation of tripropylamine for electro-chemiluminescence of
      ruthenium tris(bipyridine) complexes?

PMID- 14653007
TI  - Time-resolved second harmonic generation near-field scanning optical microscopy.

PMID- 14653008
TI  - Low temperature conductance measurements of self-assembled monolayers of 1,4
      phenylene diisocyanide.

PMID- 14653009
TI  - Conductance properties of stilbenoid molecules.

PMID- 14653010
TI  - Theoretical measurements of conductance in an (AT)12 DNA molecule.

PMID- 14653011
TI  - Stationary small and large amplitude patterns during bulk CO electrooxidation on
      platinum.

PMID- 14653012
TI  - On the representation of inflections and derivations: data from Spanish.
AB  - The four experiments reported in this paper were designed to determine to what
      extent words are lexically represented in terms of their morphological structure.
      The experiments are carried out in Spanish, a language with rich morphological
      resources, using a priming paradigm and a lexical decision task. In particular,
      they examined the pattern of priming effects in regular inflected words with
      gender and in derived words, in comparison to those produced by orthographically
      and semantically related words, by manipulating form similarity and semantic
      transparency. The results showed, on the one hand, that regular inflected words
      produced reliable facilitatory effects which are not driven just by form
      relatedness (Experiments 1 and 2). On the other hand, they showed that both
      transparent and nontransparent derived forms produced facilitatory effects
      distinct from purely orthographic and semantic effects (Experiments 3 and 4). In
      general, these findings suggest that morphological information is represented in
      the mental lexicon and may play a central role in the individuation and retrieval
      of lexical entries.

PMID- 14653013
TI  - Given-new ordering effects on the production of scrambled sentences in Japanese.
AB  - Across many languages, speakers tend to produce sentences so that given
      (previously referred to) arguments are mentioned before new arguments; this is
      termed given-new ordering. We explored the nature of such given-new effects in
      Japanese using a procedure following Bock and Irwin (1980). Speakers encoded and
      then recalled canonical (e.g., okusan-ga otetsudaisan-ni purezento-o okutta, "the
      housewife gave the housekeeper a present") or scrambled (okusan-ga purezento-o
      otetsudaisan-ni okutta) dative targets when prompted by a statement-question
      sequence. The prompting statement established one nonsubject argument of the
      dative target as given, leaving the other nonsubject argument as new. Previous
      mention was either with lexically identical content (e.g., otetsudaisan or
      purezento) or with lexically distinct but nearly synonymous content (meidosan,
      "housemaid" or okurimono, "gift"). Results showed that speakers produced
      canonical or scrambled word orders so that given arguments were mentioned before
      new, but especially when the previous mention of the given argument occurred with
      lexically identical content (replicating Bock and Irwin's English effect). These
      results show that the production of Japanese scrambled and canonical word orders
      is sensitive to given versus new status (as in English), implying that given-new
      ordering arises at the stage of sentence production where scrambling effects are
      realized.

PMID- 14653014
TI  - Judgments of grammaticality of Japanese sentences violating the principle of full
      interpretation.
AB  - Two experiments investigated the linguistic intuition of Japanese speakers in
      which they judged the grammaticality of sentences violating Chomsky's principle
      of Full Interpretation. Experiment 1 used bitransitive sentences, which included
      an extra argument that assumed a role of either subjective, dative, or objective
      on the one hand and that specified semantically a preceding argument or stood in
      par with it on the other. Findings showed that the speakers judged ungrammatical
      sentences involving a dative or an objective extra argument as more grammatical
      than those involving a subjective extra argument. Ungrammatical sentences with an
      extra specified argument were judged more grammatical than those with an extra
      par argument when the extra argument was objective. Experiment 2 used sentences
      that included a verbal noun (VN) comprising a noun followed by a verb, shita
      (did). Ungrammatical VN sentences contained two arguments given the same
      objective marker. These sentences were judged to be highly grammatical despite
      the violation of the principle. Findings suggest that speakers' actual knowledge
      of language is not fully consistent with the knowledge they are alleged by
      Chomsky to possess, including the principle of Full Interpretation.

PMID- 14653015
TI  - [Birth and development of the FESUM (European Federation of Hand Emergency
      Services)].
AB  - The European Federation of Hand Emergency Services (FESUM) was founded in France
      in 1979 and established all over the country and extended to other European
      countries in 1989. The aim of this federation is to assure the best possible
      treatment for hand injuries, thanks to the coordination of the orthopaedic or
      plastic surgery department which satisfy the standards established and controlled
      by the federation as well as the development and research in the field of hand
      trauma and applications of microsurgery. In collaboration with the French Society
      of Hand Surgery and the French College of Hand Surgery, it fulfills a triple
      mission of treatment, teaching and research in the specific field of this
      surgery. The author evokes the present role of the FESUM and the future problems
      to be solved in order to develop this specialized surgery which plays a major
      social and economic role.

PMID- 14653016
TI  - [Eight days of hand emergencies. Report of the audit carried out at the FESUM
      centers from June 3 to June 9, 2002].
AB  - All the FESUM centers in France, Belgium and Switzerland were invited to
      participate in this prospective audit, during 1 week in June 2002. In these FESUM
      centers, the patients are operated by senior hand surgeons or trainees graduated
      with a microsurgical and a hand surgery University degrees. All acute hand
      disorders, requiring surgery or not, were to be included. For every case, a
      standardized form was to be filled. This form included 22 fields concerning the
      specificities of the patient, the circumstances of the accident, the lesions and
      initial treatment up to exit of the patient out of the Hand Center. Out of the 43
      French centers, 38 (90%) participated in this study, but only 30% in the other
      French speaking countries. A total of 2360 forms were completed and analyzed,
      representing a mean of 8 forms per day center (6-147). The population was
      predominantly active men with a mean age of 31. Manual workers represented 41%,
      scholars 33%. Most of them came to the Hand Center with a non-specilized vehicle
      (86%). Emergency medical transportation was required in 130 cases (5.8%). A
      majority of the patients were treated on an outdoor basis. A 1-day admission
      concerned 29% of the patients, and 4.6% have been admitted on an indoor basis
      during several days. Work accident represented 28% of all the cases, while the
      majority was daily living (62%) or sport (15%) accidents. Closed trauma
      represented 50% of the cases. Amongst open trauma (974 cases), 862 were simple
      skin lacerations, 156 skin loss, 140 extensor tendon lacerations, 70 flexor
      tendon lacerations. A preliminary wound exploration had been performed in a non
      specialized center in 124 cases (12%). Complete amputation of some part was
      observed in 33 cases. In 32%, the initial severity of the lesion led to expect
      some degree of definitive consequences. Some kind of anesthesia was required in
      43% of the cases (local in 41%, troncular in 19%, plexical in 28% and general in
      9%). A surgical procedure was performed in 45% of the patients. Microsurgery was
      necessary in 15%, six of which were replantations. The period between
      presentation to the Hand Center and treatment was less than 1 day in 95% of the
      cases. Time of treatment was considered to be delayed in 113 cases (5%).
      Following this audit, it is considered that the FESUM centers make provision for
      the care of 120,000 cases per year, 54,000 of which needing a surgical procedure.
      This may be a small part of the total load of emergency hand surgery throughout
      the country (generally estimated over 1.4 million), but compares quite favorably
      with other European studies. We believe that improvement relies essentially on a
      better orientation of the patients whether they need a simple skill or specialist
      skill treatment. An information leaflet about orientation of hand trauma has been
      distributed to non-specialized emergency centers. Hand surgery training must be
      reevaluated inside the universitary system to avoid a dramatic lack of hand
      surgeons within a few years. A new audit will be presented next year.

PMID- 14653017
TI  - [A national campaign for the prevention of hand accidents].
AB  - The objective of this article is to propose the launch of a prevention campaign
      against hand-related accidents. This effort is motivated by: epidemiological
      studies which, despite their disparate and inhomogeneous character, show that
      hand and wrist accidents are the primary cause of traumatic lesions. They occur
      two-third of the time during daily activities. For the work-related accidents,
      they are also the primary cause of work stoppages as well as permanent
      invalidities. current legal and regulatory prevention measures have reached their
      efficacy limits. These can not be applied to errors of individuals by
      inattention, negligence or a lack of information. Sensibilization efforts in
      public education, professional training programs or direct to the public are
      still much too limited in scope and are never included in a global strategy. The
      objective of the prevention campaign will be to increase public awarenesses as a
      function of one's milieu (school, workplace, leisure, household) to identify the
      risks of hand injuries and to provide advice on how to avoid them. In this
      context, the operationalization of the campaign will pass, at the level of each
      region, by the coordination of each traditional agencies (public health, local
      government, corporations), of new partners (insurers, renters or sellers of
      handiwork and gardening equipment, etc.), as well as FESUM centres.

PMID- 14653018
TI  - [Musculoskeletal disorders of the upper extremity associated with work: from
      presentation to work maintenance].
AB  - The so called Musculo-Squeletal-Disorders in the upper extremity are frequent and
      are responsible for a significant cost. The increase in registered work-related
      affections has been quite impressive in the past few years. The type of social
      undertaking is determinant on the evolution and final outcome of the pathology.
      Our proposal for a "Passport to work continuation" follows two goals: facilitate
      and enhance the relations between medical and social workers concerned by the
      patient's course reduce the time off-work, improve prevention of work related
      pathologies, avoid dismissal for inaptitude, start earlier a vocational training,
      a rehabilitation or an adaptation of the work station.

PMID- 14653019
TI  - [Hand surgery training].
AB  - Training of the hand surgeon HAND SURGEON A CONCEPT: The hand surgeon is supposed
      to be in charge of all the hand lesions regarding, skeleton, muscles, tendons,
      nerves and vessels. He has to be able to insure reparation and coverage of all of
      them. So he is involved in all the structures, which insure integrity and
      function of the hand. PURPOSE AND WAYS OF TRAINING: To obtain the asked ability,
      the hand surgeon training has to be global and sustained by two underlying
      surgical specialities: orthopedic surgery and plastic and reconstructive surgery.
      From 2000 after many years of dealings, a Right to the Title in Hand Surgery was
      born. This Right to the Title wants to be the formal recognition of the specific
      training of the hand surgeon. For the well-recognized ancient hand surgeons they
      need to be confirmed by one's peers. Now a day the hand surgeon has to satisfy to
      this specific training: Passed the complete training and exam of the Orthopedic
      or Plastic surgery board. Spent at least 6 months as resident in the other
      underlying specialty. Passed a microsurgery examination. Passed one of the four
      national Hand Surgery diplomas (DIU/Inter-Universitary Diploma). The examinations
      have been harmonized. A common formation is delivered regarding hand surgery, the
      way of examination is the same and the formation is 2 years long. The final exam
      is presented in front of board of examiners where a teacher of one of the other
      three national diplomas is present. Spent at least 2 years in a formative hand
      surgery unit, listed by the French College of Hand Surgeons, as senior surgeon.
      Those requirements are heavy to assume and need a heavy personal involvement.
      That seems to be necessary to have an ability level as high as possible.
      Emergency surgery practice is absolutely necessary in this training. All the 17
      university formative hand surgery units listed by the French College of Hand
      Surgeons are members of the FESUM (European Federation of the Emergency Hand
      Units). Unfortunately it is non-sufficient to train the necessary number of hand
      surgeons needed in France today. So we try to obtain from the authority the
      formal recognition of a training period in private practice. Eleven out of the 28
      hand units listed as formative by the French College of Hand Surgeons are in
      private practice and may be recognized as formative in the hand surgeon training.
      That needs to create an official agreement between university and private Units.
      This part of the training is yet accepted by the Right to the Title commission
      for a 6-month training period. But this needs a legal modification or adaptation
      of the private units legal status so they will be able to offer a quite
      equivalent conditions of training. Now a days 233 surgeons in France passed the
      Right to the Title. Among them, the oldest do not have emergency practice any
      more. So unfortunately, out of 1,400,000 hand injuries a year in France, only few
      are actually cared by hand surgeons. The emergency training needs at least a
      three to four senior surgeons team, operating and caring emergencies, 24 h a day,
      365 days a year. They need to be surrounded by high-level technical facilities
      for this type of surgery. Only this type of unit may have a frequent severe hand
      traumatology practice, especially regarding microsurgery. But on the other hand a
      less complex hand unit operating only planed surgery and less complicated
      emergencies, may also be definitively formative. This only depends on the hand
      surgeon's qualification. It is only with a very demanding and high-level training
      program that our credibility as hand surgeon may be definitively established. The
      mainstay of this training is the combined action of the FESUM, the French College
      of Hand Surgeons and the DIU diploma. The Right to the Title formally confirms
      that training. For university or private unit, to be a member of the FESUM, must
      continue to guarantee a high level training regarding emergencies as in number as
      in complexity. We proposed as minimum level of practice (a year) to be a
      formative hand surgery unit: 10-15 hand and upper limb replantations; 25-30 very
      severe hand injuries (revascularization etc.); at least 1000-1500 hand surgery
      procedures.

PMID- 14653020
TI  - [Is there a role for ambulatory management of emergencies?].
AB  - The Public Health Code includes the practice of ambulatory surgery. The
      regulations are well defined and different from the practice of out patients'
      care. Good practice of this surgery necessitates the will and involvement of the
      patient, the support of his/her family which means that the operated patient is
      not alone when he/she returns home after surgery and a medical team remains in
      contact with the patient. The majority of hand trauma surgical procedures can be
      performed by ambulatory surgery. Only operations necessitating permanent post
      operative care and specific treatment as in the case of intense pain and surgical
      procedures in multi-trauma require traditional hospitalisation. To this day,
      there is no or very little litigation related to this surgical practice; the
      rules and professional obligations are the same as those for surgery with
      traditional hospitalisation. There are less risks of hospital infections because
      the operated patient spends only a few hours in the hospital. The rules specify
      that the proper functioning is under the responsibility of the co-ordinator of
      the ambulatory surgery unit.

PMID- 14653021
TI  - [Medical responsibility in hand traumatology].
AB  - The apparently benign nature of many hand injuries may lead one to underestimate
      the potentially serious consequences of these injuries. In case of significant
      residuals, patients may consider themselves victims of inadequate treatment. The
      traumatic lesions may be classified into three groups of increasing severity
      (mild, moderate and severe emergencies) which require the services of
      increasingly sophisticated treatment teams: Services d'Accueil des Urgences (SAU)
      (general emergency care facilities) for minor injuries, general surgery emergency
      services for more severe injuries, and specialized teams such as the centers of
      the "Federation Europeenne des Services Urgences Mains" (FESUM) for serious
      complicated injuries. This differentiation is correlated to the level of
      expertise of the treatment team and the quality of the technical support at their
      disposition. Proper match of the severity of injury with the level of expertise
      of the treatment team can minimize the incidence of poor results and resultant
      litigation. Personalized treatment given with the informed consent of the
      patient, and his understanding that all necessary resources will be utilized,
      will lessen the tendency for the patient to consider some less than perfect
      results as the consequence of inadequate care, and therefore, lessen the
      likelihood of litigation against the physician or hospital. The evaluation of the
      permanent impairment should be analyzed as the difference between the actual
      result and similar, if not strictly identical cases given the appropriate level
      of treatment. In order to limit the frequency of litigation, including
      unjustified lawsuits, it is necessary, as a preventive measure, to integrate
      these precautions into the plan for provision of care for hand injuries.

PMID- 14653022
TI  - [Costs of hand emergencies].
AB  - In France at the present time, there is no comprehensive registry of hand
      injuries. Three types of occurrences; motor vehicle accidents, work accidents,
      and accidents incident to activities of daily living, are covered by different
      types of insurance. It is the individual insurance companies, payers of the
      indemnification, who maintain registries of these accidents. Statistics on work
      accidents are very detailed and consistent, but they are oriented toward risk
      management. The aggregate cost of traumatic injuries to the hand is not known.
      Only large financial institutions are equipped to determine appropriate
      preventive measures and to establish premium rates based on loss experience. In
      2001, hand injuries accounted for 27% of work accidents causing loss of work of
      at least 1 day. About 29.8% of these work accidents caused permanent partial
      impairment. About 17.7% of total days lost and 18.2% of the total costs of
      permanent impairment were due to hand injuries. In the system of compensation for
      work accidents, there is a major difference in the cost according to the severity
      of the impairment. If the permanent impairment is equal to or less than 9%, a
      lump sum payment is made, but if the permanent impairment is over 9%, the worker
      receives regular payments for the rest of his life. In 2000, the average cost of
      a work injury with partial permanent impairment of over 9% was [symbol: see text]
      85,405, while the average cost of a lump sum settlement was only [symbol: see
      text] 1479, a ratio of 57 to 1. The compensation costs represent 80% of the cost
      of work accidents, while the cost of treatment, including all providers and
      institutions, makes up only 20% of the cost. Compensation for sequelae of
      accidents in the course of daily life is new for the insurance companies,
      although these accidents are frequent and often cause significant repercussions
      in the professional lives of victims because of the loss of hand function.
      Provision of optimal treatment for these traumatic injuries from the very first
      moment is the best strategy for the third party payers. Better results of
      treatment not only reduce the costs of compensation for permanent partial
      impairment, but also greatly diminish the psychological impact on the injured
      worker. In the future, the management of the costs of these work injuries will
      become a priority. Pressure from consumers, which is growing, will favor this
      trend through the intermediary of private insurance companies.

PMID- 14653023
TI  - [Annex II. FESUM internal regulations].

PMID- 14653025
TI  - Physiopathology of liver metastasis.

PMID- 14653024
TI  - [Surgery education: past, present and future].

PMID- 14653026
TI  - The role of nuclear medicine in the staging and management of liver metastases.

PMID- 14653027
TI  - Local ablative treatments for liver metastases: the current situation.
AB  - Surgical resection is the optimal treatment for liver metastases. However, due to
      their multifocality and/or insufficient remnant liver volume, the majority of
      liver metastases are unresectable. For this reason, several local ablative
      techniques have been developed, aiming to produce selective tumour destruction
      and thus increase the rate of patients amenable to curative-intent treatments.
      Among these techniques, cryoablation and radiofrequency ablation only have proven
      to have a curative potential, while transarterial chemoembolization and alcohol
      injection should be considered as palliative options only. The local recurrences
      after cryoablation and radiofrequency are equivalent, inferior to 10%, highly
      dependent of selection criteria. In contrast, morbidity is significantly
      increased after cryoablation, leading most of the teams to prefer the
      radiofrequency approach. Two major limitations for radiofrequency are, first, the
      risk to provoke heat biliary lesion in case of metastases located proximally to
      hilar plate, and second, the risk of insufficient ablation due to a cooling
      effect in case of metastases near to major vessels. Keeping in mind these
      limitations, selective use of radiofrequency may offer a significant benefit by
      allowing complete tumour clearance in patients with unresectable liver
      metastases.

PMID- 14653028
TI  - Liver resection for noncolorectal, nonneuroendocrine metastases.
AB  - In noncolorectal, nonendocrine liver metastases, the role of surgery is less
      define than in colorectal or neuroendocrine cancer. This role is marginal as
      liver is not the primary site of metastases of these cancers. Less than 2 to 5%
      of the patients with these malignancies might be one day considered as potential
      candidates for liver resection, as most patients suffer from extra hepatic tumour
      spread at the time they develop liver involvement. However, in these few cases
      with liver metastases only, as no other therapeutic option may provide mid- or
      long-term tumour-free survival, liver resection is indicated in resectable liver
      metastases. Some prognostic factors have been established in the literature from
      the few published series: unique versus multiple hepatic metastases, unilobar vs
      bilobar, metachronous vs synchronous, R0 vs R1 or R2 liver resections. The type
      of primary tumour is also of great importance, as cutaneous melanoma, pancreatic
      and gastric adenocarcinoma have a very bad prognosis for liver resection of
      metastases, even after R0 resection. In these cases, percutaneous or laparoscopic
      radiofrequency ablation may find its place. In sarcoma, breast carcinoma, uveal
      melanoma, and genitourinary cancers, liver resection may provide satisfactory
      long-term results in selected cases, and is the standard of care for isolated,
      resectable metastasis. However, due to the scarcity of indication of liver
      resection for noncolorectal, nonneuroendocrine metastases, the decision should be
      multidisciplinary, and the patients should be informed of the advantages and
      pitfalls of the surgical procedure.

PMID- 14653029
TI  - The causes of early deterioration in renal function following successful renal
      interventions.
AB  - The available evidence suggests that endovascular intervention in renovascular
      renal failure is a safe and efficacious procedure. However there is a significant
      incidence of early renal deterioration following angioplasty or stenting.
      Complications are limited by training and experience but inevitably still occur.
      Cholesterol embolization and contrast nephrotoxicity may be more important. This
      review describes the complications and considers whether the kidney should be
      protected from the effects of cholesterol and contrast and, if so, whether this
      can be done safely and economically?

PMID- 14653030
TI  - Angiogenesis--a new goal in peripheral artery occlusive disease therapy.
AB  - The vasculature is mostly quiescent in the normal adult, with the exception of
      the growth of new blood vessels during the female reproductive cycle. Recent
      advances in the knowledge concerning the molecular changes and the identification
      of genetic events in this vascular quiescence, as well as in vascular growth, has
      led to an increasing number of studies in which these phenomena are manipulated.
      Angiogenesis is the growth of new vessels from existing ones. Although new vessel
      formation is involved in many pathologic situations, like tumour growth,
      therapeutic angiogenesis has been presented as a novel method for the treatment
      of ischemic diseases, like peripheral arterial occlusive disease (PAOD). In
      experimental studies therapeutic angiogenesis has been produced by recombinant
      growth-factor protein application as well as by growth factor gene therapy. Most
      widely studied factors belong to vascular endothelial growth factor (VEGF) or
      fibroblast growth factor (FGF) families. Studies have also shown that, angiogenic
      growth factors stimulate endothelial cell migration and accelerate endothelial
      repair by enhancing post-injury re-endothelization. In clinical studies
      angiogenic therapy has been evaluated in patients with severe vascular diseases.
      The results have revealed that therapy is well tolerated as well as safe and that
      angiogenic therapy has a clear biologic effect. However, controlled studies are
      still needed to answer the question whether therapeutic angiogenesis offers a
      real clinical benefit to patients with PAOD.

PMID- 14653031
TI  - Redo valve surgery nowadays: what have we learned?
AB  - Re-operative valvular surgery is common nowadays. Increased mortality and
      morbidity are generally associated. Re-operations in cardiac surgery are
      technically more difficult because of adhesions and a more advanced cardiac
      status of the patient. Results reported 20 years ago carried a high mortality
      risk. Experience and technological evolution have produced a substantial
      reduction in postoperative mortality nowadays. The present review focuses on
      historical results of redo valve surgery, risks factors for postoperative
      mortality, technical progress and surgical strategies contributing to better
      results.

PMID- 14653032
TI  - Surgical management of recurrent colon haemorrhage of unknown origin.
AB  - Although both endoscopy and angiography have profoundly changed the management of
      lower GI bleeding, the choice, timing and sequence of these procedures as well as
      the indications for surgery remain a matter of debate. In cases of massive
      bleeding, early angiography should be performed as the first choice examination.
      When this fails, exploratory laparotomy, including peroperative colonoscopy after
      colonic wash-out, should not be discarded as a diagnostic possibility. If no
      source of bleeding is identified notwithstanding colonoscopic evaluation in
      excellent conditions, and it can be assumed that the bleeding has ceased, a
      conservative attitude may reasonably be advocated.

PMID- 14653033
TI  - Ischemic preconditioning: enough evidence to support clinical application in
      liver surgery and transplantation?
AB  - Ischemia-reperfusion injury of the liver causes severe organ dysfunction after
      both extended liver resections and liver transplantation. In experimental models,
      ischemic preconditioning has repeatedly been shown to protect the liver from
      injury after warm and cold ischemia-reperfusion. Herein, we summarize the
      experimental and clinical evidence considering protection of tissue by ischemic
      preconditioning and we conclude that it is now time to initiate prospective
      randomized multicenter trials, in order to confirm the benefit of ischemic
      preconditioning for the patients undergoing major liver surgery and liver
      transplantation.

PMID- 14653034
TI  - Recurrent "spontaneous" pneumoperitoneum: a diagnostic and therapeutic dilemma.
AB  - The finding of intraperitoneal free gas usually indicates a perforated abdominal
      viscus, and requires emergency surgery. In a minority of cases, no perforation
      can be found, a situation that can be classified as "spontaneous"
      pneumoperitoneum. A conservative approach may be considered if clinical signs are
      minimal, particularly when peritoneal signs, fever and leucocytosis are absent.
      The various causes of spontaneous pneumoperitoneum are discussed.

PMID- 14653035
TI  - Hand-assisted laparoscopic aortoiliac surgery: preliminary report of 25 cases.
AB  - INTRODUCTION: Since a few years vascular surgeons are developing laparoscopic
      vascular techniques. We report our preliminary results in this area, using the
      hand-assisted technique. MATERIALS AND METHODS: Twenty-five patients were
      operated between February and December 2001 using the HandPort-system.
      Indications were occlusive aortoiliac disease or infrarenal aortoiliac aneurysmal
      disease. RESULTS: Mean operating time was 180'; mean aortic clamping time was
      37'; mean blood loss was 521 mL. Mean laparotomy length was 7.9 cm. A conversion
      to a larger laparotomy was necessary in two patients. Mean hospital stay was
      seven days. Operative mortality was 4% (one postoperative death). CONCLUSIONS:
      Hand-assisted laparoscopic aortoiliac surgery is feasible in community hospital
      settings.

PMID- 14653036
TI  - Management of oesophageal perforation after delayed diagnosis: the merit of
      tissue flap reinforcement.
AB  - Oesophageal perforation remains a life-threatening situation and its management
      represents a challenge for the surgeon, especially if diagnosis has been delayed.
      In most cases, a surgical approach is indicated. Simple primary repair often
      result in leakage. In order to avoid leakage, the primary repair should be
      buttressed with some kind of tissue flap. We here report our experience with 15
      esophageal perforations and 10 tissue flap reinforcements performed during the
      last decade. The different types of tissue flap are illustrated and their results
      are compared with more aggressive alternatives such as oesophagectomy, T-tube
      drainage and oesophageal exclusion.

PMID- 14653038
TI  - Cutaneous cysts: a plea for systematic analysis.
AB  - So-called cutaneous cysts are extremely frequent tumours that could need surgical
      attention. Most of the time, due to their quite pathognomonic clinical
      presentation and indolent course, they are simply enucleated. Often, the clinical
      diagnosis is easily confirmed at surgery by the typical appearance of a cystic
      formation filled with a creamy fluid. It is frequent for such "typical" lesions
      to escape histological investigation following removal. However, some mimicking
      lesions could also be found as "cutaneous cysts" and have quite different
      prognoses. This paper present five patients with such lesions, three basal cell
      carcinomas, one benign proliferating trichilemmal cyst and a malignant
      proliferating trichilemmal cyst. None of the lesions was clinically
      distinguishable from a classical epidermis cyst.

PMID- 14653037
TI  - A prospective randomized study of Lichtenstein open tension-free versus
      laparoscopic totally extraperitoneal techniques for inguinal hernia repair.
AB  - Ideal technique for effective inguinal hernia repair is still controversial.
      Although open tension free mesh techniques of inguinal hernia repair offers good
      results but the superiority of laparoscopic technique was reported for
      postoperative pain, discomfort and earlier return back to work. A prospective,
      randomized study was conducted to compare Lichtenstein open tension free mesh
      technique with the laparoscopic totally extraperitoneal technique. 62 male
      patients with Lichtenstein open tension free mesh technique and 61 male patients
      with totally extraperitoneal technique were operated and compared
      postoperatively. The patients were followed-up for 24 months with a median of 18
      months. In terms of recurrence, postoperative pain, analgesic requirement,
      complications, hospital stay length, duration of limitation of normal daily
      activities there were no significant differences between the two groups.
      Operating time for totally extraperitoneal hernia repair was 16 minutes longer
      than Lichtenstein open tension free technique. The totally extraperitoneal
      technique was considerably expensive than Lichtenstein technique, however the
      duration of returning back to work was shorter in patients repaired with totally
      extraperitoneal technique. In conclusion in primary inguinal hernia repair
      Lichtenstein technique should be preferred and the totally extraperitoneal
      technique should be considered for recurrent and bilateral hernias.

PMID- 14653039
TI  - Anal canal pressure in anal fissure before and after internal sphincterotomy.
AB  - PURPOSE: To assess whether the anal canal pressure is increased in patients with
      a chronic anal fissure and to examine the effects of internal anal sphincterotomy
      (IASy) on this pressure. MATERIALS AND METHOD: Anorectal manometry was performed
      in 28 patients in whom an anal fissure had been diagnosed by means of physical
      examination and anuscopy. After IASy the manometric measurement was repeated on
      the 15th postoperative day and compared with the value obtained in twelve healthy
      volunteers. RESULTS: In patients with chronic anal fissure, the mean maximal
      resting pressure (MRP) was found to be 112.38 +/- 8.35 cm H2O pre-operatively and
      66.23 +/- 8.44 cm H2O postoperatively, with a significant drop after IASy (p <
      0.001). The MRP value was found as 75.16 +/- 10.22 cm H2O in the control group.
      The pre-operative MRP values in patient group was found to be higher than in the
      control group (p < 0.001). CONCLUSIONS: In patients with chronic anal fissure,
      the anal canal MRP pressures decreased significantly following IASy and complete
      clinical recovery was attained.

PMID- 14653040
TI  - Unusual complications of preperitoneal mesh implantation in the treatment of
      inguinal hernia.
AB  - More and more prosthetic materials are being used in the treatment of inguinal
      hernia. This report deals with some unusual but devastating complications,
      occurring after preperitoneal mesh implantation. A 56-year old male patient
      underwent a Stoppa-repair for a bilateral inguinal hernia. Two years
      postoperatively, a localized abdominal wall abscess was treated with antibiotics
      and drainage. A barium enema and a CT-scan of the abdomen were performed to rule
      out an enteric fistula; the CT-scan unexpectedly revealed a tumoral mass
      involving the sigmoid colon, and an explorative laparotomy was done.
      Peroperatively, part of the mesh was found to penetrate the bowel wall and a
      sigmoidectomy with removal of the mesh was performed. Two years later, ingrowth
      of the urinary bladder by the remains of the mesh was the unfortunate
      peroperative finding when the patient was operated on for an inflammatory mass,
      involving the bladder wall. The patient needed two more interventions for
      persisting wound fistulas. All the remains of the mesh have been removed and all
      fistulas have been widely excised. Nowadays, the patient is recovering well with
      complete healing of all wounds. Although infection of prostheses used in the
      treatment of hernias has been described, late and serious complications related
      to mesh implantation, such as perforation of the colon and the bladder, have
      seldom been reported.

PMID- 14653041
TI  - Residual appendicitis following incomplete laparoscopic appendectomy.
AB  - Growing popularity of laparoscopic interventions must bring along a thorough
      knowledge of possible complications inherent to the laparoscopic technique. With
      these two cases of residual appendicitis following incomplete appendectomy, the
      authors want to warn for this complication. Surgeons should be aware of residual
      appendicitis as a possible cause of acute abdomen at any time following a
      laparoscopic appendectomy.

PMID- 14653042
TI  - Diaphragmatic endometriosis: diagnosis and surgical management--a case report.
AB  - Endometriosis has been observed in 8 to 15% of the women of reproductive age.
      Occasionally it can be found outside the pelvis, its usual location. Rather
      exceptionally it is located on the diaphragm. A case report of preoperatively
      diagnosed bilateral diaphragmatic endometriosis is presented and its surgical
      treatment will be discussed.

PMID- 14653043
TI  - Abdominal actinomycosis: a case report.
AB  - Actinomycosis is an anaerobic infection caused by actinomycetes, which are part
      of the normal flora in the intestinal, anal and genital tracts. Although the
      infection is often cured medically with appropriate antimicrobial therapy,
      diagnosis is usually made surgically. We report the case of a 41 year-old woman
      with intra-abdominal mass secondary to extensive actinomycosis involving the
      hepatic flexura. She required emergency surgery during which the mass was
      excised. A review of the literature on abdominal actinomycosis during the last 20
      years is reported. Emergency surgery has been rarely described in this condition.
      Although the incidence of actinomycosis has decreased, the abdominal form has
      been observed with increasing frequency: it could be the result of prolonged use
      of intra-uterine device. Abdominal actinomycosis is an extremely rare infection
      that can mimic multiple disease processes and requires accurate diagnosis for
      successful therapy.

PMID- 14653044
TI  - Emergency hepato-renal artery bypass using a PTFE graft.
AB  - A 51-year-old patient suffering from Buerger's disease with bilateral lower limb
      amputation and Leriche syndrome presented with uncontrollable hypertension and
      renal failure caused by right renal artery subocclusive stenosis associated with
      an occluded left renal artery and atrophic kidney. He underwent a right hepato
      renal bypass grafting using an externally supported polytetrafluorethylene (PTFE)
      graft. Renal function improved markedly and hypertension could be controlled by
      standard antihypertensive treatment. Normal right renal function was maintained
      at one-year follow-up.

PMID- 14653045
TI  - Neurovascular compression by a subpectoral lipoma. A case report of a rare cause
      of thoracic outlet syndrome.
AB  - BACKGROUND: Lipomas are benign soft tissue tumours, progressively expanding in
      volume. Beside frequent aesthetic consequences, lipomas can also exert pressure
      on surrounding tissues and structures. MATERIALS AND METHODS: A case of a
      subpectoral infraclavicular lipoma compressing the axillo-subclavicular
      neurovascular bundle, produced unilateral brachialgia, thereby simulating a
      Thoracic Outlet Syndrome. The expansive, but non-infiltrative, nature of the
      lipoma allowed local excision in the vicinity of the brachial plexus and
      infraclavicular vascular structures. RESULTS: Surgical removal of the lipoma
      resulted in complete remission of symptoms in the left arm and hand. CONCLUSIONS:
      In the presence of unilateral brachialgia, a subpectoral tumour causing a
      Thoracic Outlet Syndrome should always be excluded in the absence of other
      relevant pathology.

PMID- 14653046
TI  - Surgical treatment of coronary artery fistula with aneurysm.
AB  - Two operations for coronary artery aneurysm with fistula are reported. This rare
      congenital malformation can be associated with acute and chronic complications.
      Surgical treatment is generally recommended. The surgical strategy remains
      controversial and is discussed. Retrograde cardioplegic cardiac arrest and
      retrograde dissection of the fistula are favoured. Conservative treatment of the
      dilated coronary segments was adopted. In both cases, the postoperative course
      was uneventful and no residual shunts were diagnosed at postoperative
      echocardiography.

PMID- 14653047
TI  - In vitro allergy diagnosis: comparison of a new method of fully automated
      determination of specific IgE, using Immulite 2000 compared with UniCAP 100.

PMID- 14653048
TI  - Nasal cytokine modulation by montelukast in allergic children: a pilot study.
AB  - BACKGROUND: Allergic rhinitis and asthma are characterized by chronic
      inflammation due to a Th2 cytokine polarization. Leukotrienes receptor
      antagonists have been shown to be effective in both diseases. OBJECTIVE: Aim of
      the study was to evaluate the modulation by the antileukotriene montelukast on
      Th2 and Th1 cytokines in allergic rhinitis. METHODS: Fourteen school children
      affected by persistent allergic rhinitis (PAR) and exercise-induced asthma (EIA)
      underwent a nasal lavage before and after a two-week treatment with montelukast.
      A panel of cytokines, including IL4, IL13, and IFN gamma, was measured by
      immunoassay on nasal lavage samples. RESULTS: Montelukast treatment induced a
      significant decrease of IL4 and IL13 levels (p < 0.001, for both comparisons),
      and a significant increase of IFN gamma (p < 0.001). CONCLUSIONS: Montelukast
      treatment reversed a typical Th2 cytokine pattern (IL4 and IL13) toward a Th1
      (IFN gamma) predominance in children with PAR and EIA. This effect could be
      considered relevant for long term allergic inflammation control and of interest
      when treating EIA with concomitant PAR.

PMID- 14653049
TI  - The pattern of indoor and outdoor respiratory allergens in asthmatic adult
      patients in a humid and desert newly developed country.
AB  - BACKGROUND: Studies have shown that allergens are very important sensitizing
      agents in patients with asthma. Respiratory disorders such as asthma and allergic
      rhinitis are common in the State of Qatar. OBJECTIVE: To characterize the most
      frequent indoor and outdoor respiratory allergens involved in bronchial asthma
      and allergic rhinitis in the State of Qatar. DESIGN: A hospital-based prospective
      study conducted. SETTING: Allergy Laboratory at the Hamad General Hospital and
      Hamad Medical Corporation, Doha, State of Qatar. PATIENTS: Adult patients over 12
      years of age diagnosed with bronchial asthma and/or allergic rhinitis who were
      referred for allergy skin pick test. 1106 adult patients recruited with
      respiratory diseases of suspected allergic origin who attended Allergy Clinic at
      the Hamad General Hospital, during three years from January 2001 to April 2003.
      Total of 1106 whom 607 were females (54.9%) and 499 were males (45.1%) and their
      mean was age 30 years (12-48). METHODS: Skin Prick Test [SPT] was performed on
      1106 patients for common allergens whom The blood sample was taken for measuring
      specific IgE concentration. RESULTS: There were 1106 patients studied and 569
      patients (51.4%) had positive skin prick test. All patients expressed clinical
      allergy, 464 patients (52%) had asthma and rhinitis, 286 patients (32%) had
      rhinitis alone and 137 patients (15%) had asthma alone. The population sample had
      a higher prevalence of diagnosed asthma among females (32.7%) than in males
      (29.8%) and also skin conditions such as eczema, pruritus, and urticaria higher
      in females (9.1%%) than males (7.0%). Similarly, males had higher prevalence of
      allergic rhinitis (86.0%) than in females. There were 318 (55.9%) patients whose
      asthma developed before they were 10 years old. The percentage of asthmatic
      patients with a positive family history of asthma was 44%. The most common
      allergens detected in order of frequency were Dermatophagoides Pteronyssimus (Der
      p l) in 248 patients (41.6%), Dermatophagoides Farinae (Der f l) in 220 patients
      (36.9%), Cockroach allergen (Bla g l) in 192 patients (32.2%). The study showed
      that females are more exposed to pollen, grasses and tress, but males are mostly
      exposed to mites and insects. Furthermore, Molds and Yeast were common among
      males. CONCLUSION: In conclusion, the frequency of indoor and outdoor allergens
      in state of Qatar, based on skin prick test study showed the dominance of house
      dust mites, pollen, grasses which are more or less same to other countries with
      similar and even with different climate. Reduced exposure to these agents will
      help control raising severity of these disease.

PMID- 14653050
TI  - Rhinitis in pregnancy.
AB  - About 30% of women suffer from nasal symptoms during pregnancy. The hormonal
      changes occurring during pregnancy favour per se mucosal oedema and relaxation of
      smooth muscles, thus contributing to nasal congestion. The most common forms of
      rhinitis are allergic, drug-induced, infectious and vasomotor rhinitis. In
      addition to the detrimental effects that rhinitis can have on quality of life, it
      is important to correctly treat rhinitis itself since it can influence
      concomitant asthma, as underlined in ARIA document. In pregnancy, the safety
      profile of drugs is the primary item to be considered. The American FDA pointed
      out that foetal damage could not be totally excluded with the majority of
      antirhinitis drugs. It is recommended to use "older drugs" because more data
      about their safety are available. Cromones are the safest drugs but, although
      they need multiple daily administrations. Antihistamines should be considered as
      second choice drugs, and their use is not recommended during the first three
      months of pregnancy. Topical steroids are useful in moderate-severe rhinitis,
      being beclometasone the most documented molecule. Topical vasoconstrictors should
      not be used continuously because they can induce pharmacological rhinitis. It is
      not recommended to start specific immunotherapy in pregnancy but it can be
      continued in patients who benefit from its use. Infective rhinitis should be
      treated with beta-lactams, cephalosporins or macrolides. Finally it is important
      to evaluate the cost/usefulness ratio before any drug prescription.

PMID- 14653051
TI  - [Totally implantable artificial heart: a new stage].

PMID- 14653052
TI  - [Totally implantable completely electric artificial heart: "AbioCor"].
AB  - The fully implantable complete electric artificial heart "AbioCor" is the
      ultimate stage in the 3rd generation assistance systems. It has been authorized
      for clinical use since last year by the Food and Drug Administration (F.D.A.). It
      is an electrohydraulic heart developed by Abiomed. It consists of implanted
      internal components: the cardiac pump, an internal lithium battery, a controller
      and an internal coil allowing electrical energy transfer across the skin, and
      external components: an external coil and external batteries. The one-piece heart
      includes two ventricular chambers: right and left. All of the surfaces in contact
      with blood as well as the four three-leaved valves are made of polyurethane. An
      electro-hydraulic energy converter powers the ventricles. A stroke volume of 60
      to 65 ml allows an output of between 4 and 10 L.min-1. Between 2 July 2002 and 4
      November 2002, seven males, aged between 51 and 70 years, underwent implantation.
      They were suffering from ischaemic cardiopathy (6 cases) or idiopathic dilated
      cardiopathy (1 case). Among the late complications, 3 severe embolic
      cerebrovascular accidents occurred. Four late deaths occurred.

PMID- 14653053
TI  - [Changes in reperfusion strategies in the acute phase of myocardial infarction
      from 1988 to 2001].
AB  - The objective of this study was to evaluate the evolution of therapeutic
      strategies in the course of myocardial infarction. Two successive periods were
      studied: 1988/96 (700 patients) and 1996/2001 (700 patients). The following
      parameters were compared: patient characteristics, management methods, and
      results on the hospital morbidity and mortality. The patient characteristics were
      little changed, in terms of age and sex, with a drop in the frequency of anterior
      infarcts during the second period (46 vs 51%, p = 0.0001). The average delay to
      admission remained stable over both periods, 186 vs 189 min. During the second
      period, primary angioplasty was favoured (66 versus 44%, p = 0.0001), associated
      with a wider use of stents (47 against 4%, p = 0.0001) and anti GP IIb/IIIa (24
      against 0.5%, p = 0.0001). In the acute phase, TIMI3 reperfusion was obtained in
      81% of cases (88/96 period) against 88% during the second period (p = 0.02). The
      hospital mortality was reduced by 1.2% (8.9 against 7.7%, NS). Without
      cardiogenic shock, the mortality was comparable between the two groups (5%),
      whereas it diminished in the small group of patients (5%) in cardiogenic shock,
      from 76 to 66% (NS). Haemorrhagic complications were reduced, but the rate of
      symptomatic reocclusion remained stable (2.5%). With multivariate analysis, the
      independent predictive mortality factors were identical in the two groups: age
      and cardiogenic shock on admission. Currently, TIMI3 reperfusion is possible in
      close to 90% of patients in the acute phase of infarction. Our efforts should
      focus on earlier management, especially for older patients, too often excluded
      without reason, and for those in cardiogenic shock, which constitutes a
      therapeutic quest for the future. The theory of angioplasty facilitated by anti
      GP IIb/IIIa and/or prehospital thrombolysis must be evaluated scientifically with
      the goal of early and efficient reperfusion for the greatest number of patients.

PMID- 14653054
TI  - [Study of left ventricular function at rest and post-exercise with thallium-201
      myocardial scintigraphy synchronized with ECG].
AB  - ECG-gated Thallium 201 myocardial scintigraphy provides a simultaneous evaluation
      of left ventricular perfusion and function. The aims of this study were to
      determine the changes in left ventricular ejection fraction (LVEF) after exercise
      and at rest 4 hours after exercise and to compare the results with changes in
      myocardial perfusion and the severity of the coronary artery disease. Sixty-four
      men with myocardial ischaemia on scintigraphy who had undergone coronary
      angiography showing significant lesions within 3 months, were compared with 38
      normal men. The ejection fraction was calculated with a validated programme
      (QGS). The change in LVEF between the post-exercise and resting measurement 4
      hours after exercise (delta LVEF) was compared in the normal and ischaemic groups
      (+7 +/- 6.8% vs -5.6 +/- 5%, p < 0.001). The extent of the ischaemia (percentage
      myocardium unperfused) was significantly greater in the 34 patients who had an
      over 5% reduction in LVEF on exercise compared with the 30 others who has a less
      than 5% reductionin LVEF (11.8 vs 6.3%, p < 0.001). There was a linear
      correlation between the degree of ischaemia and delta LVEF in the 30 patients
      without a history of infarction (r = -0.76, p < 0.01). The delta LVEF also
      correlated with the number and site of the coronary lesions. The authors conclude
      that in this male population, ECG-gated Thallium 201 myocardial scintigraphy can
      demonstrate a decrease in LVEF after exercise in ischaemic coronary patients
      whereas it increases in normal subjects. This decrease in LVEF on exercise is
      correlated with the extent of ischaemia and the severity of the coronary disease
      and should therefore be taken into account in patient management.

PMID- 14653055
TI  - Non-invasive blood pressure variability in chronic heart failure: characteristics
      and prognostic value.
AB  - BACKGROUND: Short-term variability of blood pressure can be used as an index of
      sympathetic vascular modulation and has been studied in patients with
      hypertension. AIM: The aim of this study was to characterise blood pressure
      variability (BPV) and its prognostic value in patients with congestive heart
      failure. METHODS AND RESULTS: 104 patients with congestive heart failure due to
      ischemia (n = 104) or idiopathic cardiomyopathy (n = 50) in New York Heart
      Association (NYHA) class II (n = 50), III (n = 71), IV (n = 33), and 40 healthy
      subjects were studied. The mean ejection fraction was 0.33 +/- 0.10. Continuous
      non-invasive BP recordings were obtained for 3,600 seconds with a
      photoplethysmographic finger device in patients and control subjects at rest.
      Patients with chronic heart failure (CHF) had significantly less pronounced BPV
      than control subjects. Diastolic blood pressure (DBP) variability was related to
      left ventricular ejection and to peak oxygen uptake. BPV was not different in
      patients with ischemic or idiopathic CHF. During the mean follow up (+/- SD) of
      565 +/- 215 days, 44 patients died (28.6%). All deaths were cardiac related.
      Cox's univariate analysis identified the following factors to be predictors of
      death: peak oxygen uptake (p = 0.01), ejection fraction (p = 0.008), and among
      BPV parameters: total spectral amplitude (TA) for DBP (p = 0.002), very low
      frequencies over total amplitude (VLF/TA) for DBP (p = 0.005) and for mean blood
      pressure (MBP) (p = 0.03), and very low over high frequencies ratio (VLF/HF) for
      DBP (p = 0.002). Multivariate analysis showed that BPV predicted survival
      independently of EF or peak VO2. Kaplan-Meier survival curves revealed that
      VLF/TA < 55% for DBP, MBP and SBP are useful risk factors. One-year survival in
      patients with VLF/TA < 55% of DBP was 53% compared with 95% in those with VLF/TA
      > 55% (p = 0.005). CONCLUSIONS: Decreased BPV in patients with CHF is related to
      left ventricular dysfunction. Analysis of BPV can identify patients with CHF who
      have an increased risk of cardiac death.

PMID- 14653056
TI  - [Pheochromocytoma: 25 years of experience. Report of 199 cases].
AB  - The methods for diagnosing pheochromocytoma have progressed in 25 years, so
      changing the clinical, biological and tumoral presentations. The authors compare
      the features of 199 patients with pheochromocytoma operated between 1975 and 2001
      by quartiles. The frequency and known duration of hypertension, plasma
      adrenaline, the tumour size and proportion of cases which were malignant from the
      outset, have decreased over the observation period (p < 0.01). The average age
      and proportion of familial cases or associated with diabetes or those of
      asymptomatic patients (with incidentaloma), has not changed significantly. The
      pheochromocytoma were adrenal (104 right, 60 left, 12 bilateral) or ectopic (23)
      and 13 were malignant from the outset. Over a median 5 year follow-up, 35
      pheochromocytomas recurred either in the benign or malignant forms. Recurrences
      of tumours of the right adrenal were more common than those of the left adrenal
      gland (p = 0.03). In conclusion, pheochromocytomas are diagnosed earlier, at a
      stage when the tumours are smaller and less secreting. The higher incidence and
      recurrence rate of right adrenal pheochromocytoma remain unexplained.

PMID- 14653057
TI  - [Evaluation of postoperative mortality and quality of life of patients over 75
      years of age after valve replacement for aortic stenosis. Report of 110 cases].
AB  - The authors carried out a retrospective study of short and long-term mortality
      after aortic valve replacement and assessed the quality of life by the IRIS scale
      in patients over 75 years of age operated for severe aortic stenosis at the
      University Hospital of Brest between June 1990 and March 1995. The hospital files
      of 110 consecutive patients (71 women, 39 men; average age 78 +/- 2 years, range
      75-85 years) were studied. The pre- per- and postoperative data was studied. Each
      survivor was contacted by telephone during the year 2000 and a health and IRIS
      quality of life questionnaire was sent to them. Precise information about
      patients who had died was obtained from the family and/or medical practitioner.
      In the preoperative period, 30.9% of patients had left ventricular failure. The
      average aortic valve surface area was 0.53 +/- 0.12 cm2. Of the patients who
      underwent coronary angiography (60%), one third had significant coronary lesions.
      Coronary artery bypass surgery was associated with aortic valve replacement in
      10% of cases. Biological prostheses were used in 108 patients. The operative
      mortality was 8.2%. One year, 5 year and 10 year survival rates were 89.9%, 75.5%
      and 33.3% respectively. Of the survivors, 16.7% were in institutional care and
      83.3% lived at home. A total of 77.8% were readmitted to hospital, about half of
      them for cardiac problems. Cardiac treatment was prescribed for 97% of patients.
      The quality of life questionnaire was completed by 35 patients: the quality of
      life was better than average in nearly 83% of these patients. Aortic valve
      replacement for aortic stenosis in patients over 75 years of age improves life
      expectancy which is almost the same as that of the normal population of the same
      age, and improves the quality of life by restoring functional autonomy, enabling
      the majority of them to live in their own houses most of the time.

PMID- 14653058
TI  - [Evaluation of the hemodynamic profile of mitral Saint Jude Medical prostheses in
      the early and late postoperative period].
AB  - This study was to estimate the Doppler haemodynamic profiles of 56 prosthetic
      mitral valves (St Jude prosthesis) in the premature post-operating period, to
      study the correlation of the prosthetic area calculated by Doppler method
      (continuity equation (CE) and pressure half times (PHT)) and the area of the
      effective orifice in the post-operating premature period, in 6 weeks and after 6
      months. The values of peak gradient and mean gradient at six week and at 12.5
      months were not significantly different from those obtained in the premature
      exam. The prosthetic area calculated by continuity equation (ACE) in the
      premature postoperative period was significantly different between the various
      size (p = 0.0001). The (ACE) measured at 6 weeks and late (12.5 months), was not
      significantly different from that calculated in the premature exam (respectively
      p = 0.79 and p = 0.8). The (PHT) was very variable even within the different size
      of the prosthesis, however values measured at six weeks and in the late exam was
      not different from that calculated in the premature exam. In absence of
      complications, it seems to us that we can satisfy with using as reference exam
      data obtained in the premature exam.

PMID- 14653059
TI  - [Endothelin-1 receptor antagonists in heart failure].
AB  - Endothelin-1 is a vasoconstrictor peptide playing an important role in the
      pathophysiology of heart failure. Endothelin-1 acts after fixation to 2 specific
      receptors: type A, responsible for vasoconstriction and type B, at the start of
      transient vasodilation and participating in clearance of the hormone. The
      experimental results in various animal models have demonstrated beneficial
      haemodynamic and clinical effects of the mixed or specific antagonists of the
      type A receptor. The preliminary results of studies conducted in man have
      confirmed the beneficial haemodynamic effects with lowering of pulmonary
      pressures, lowering of vascular resistance, and increase in cardiac output. On
      the other hand, the results of clinical studies have been disappointing, with a
      neutral effect of an oral mixed antagonist, bosentan, compared to placebo in the
      only study of morbidity and mortality. These results have put a brake on the
      development of this therapeutic class in heart failure.

PMID- 14653060
TI  - [Pitfalls in tamponade: main error causes in the clinical and echocardiographic
      diagnosis].
AB  - The diagnosis of tamponade is confirmed by Doppler echocardiography. Early
      examination by this means is capital which implies easy access to this facility
      whenever the clinician suspects this condition. The diagnostic value of classical
      clinical and Doppler echocardiographic signs requires a model of circumferential
      pericardial effusion exerting compressive effects in the context of spontaneous
      ventilation. The underlying pathologies, assisted, ventilation, localised
      pericardial effusions, are responsible for over- or under-diagnostic errors.

PMID- 14653061
TI  - [Coronary dissection associated with exercise: unusual cause of myocardial
      infarction].
AB  - A case of coronary artery dissection occurring immediately after weight training
      is reported in a young adult with no cardiovascular risk factor. The patient had
      an anterior myocardial infarction treated by primary coronary angioplasty and
      stenting. Other rare but similar cases have been reported in the literature with
      a generally poor prognosis. The physiopathological mechanisms acting during
      exercise or the immediate recovery period are thought to be either trauma of the
      arterial wall by the myocardium itself or coronary artery spasm. Present
      management of this condition is based on coronary angioplasty with stenting.

PMID- 14653062
TI  - [Unusual cause of myocardial infarction].
AB  - The authors report the case of a woman with an acute myocardial infarction in
      whom coronary angiography performed a few hours earlier was completely normal.
      Transoesophageal echocardiography showed two thrombi in the left atrial appendage
      confirming the thromboembolic mechanism of this infarct.

PMID- 14653063
TI  - [Isolated right heart failure in acute lymphocytic myocarditis].
AB  - The authors report a case of acute myocarditis, presenting with signs of isolated
      right heart failure which was progressive and fatal. This is a very rare
      observation which poses diagnostic problems. A review of the literature showed
      only 4 previous reports, all diagnosed at autopsy, in which the diagnosis was not
      suspected in vivo. In our case, echocardiography raised the possibility of
      myocarditis at an early stage, although the initial clinical signs were atypical
      and did not indicate right ventricular disease. It is particularly important to
      detect right ventricular involvement, especially when associated with left
      ventricular disease, as the prognosis is very poor. This case report illustrates
      the difficulty of the differential diagnosis and shows the diagnostic and
      prognostic value of echocardiography when interpreted in the clinical and
      electrocardiographic context.

PMID- 14653064
TI  - [Left atrial thrombus in multiple myeloma treated with thalidomide].
AB  - The occurrence of a left atrial thrombus without a haemodynamic predisposing
      factor (arrhythmia, mitral valvulopathy, severe left ventricular dysfunction) is
      a rare event. We report a case during the progression of refractory myeloma, four
      months after stopping treatment with thalidomide. The promoting haemodynamic
      factors for left atrial thrombosis in sinus rhythm, described in the literature,
      had been excluded. In our case the potential role of thalidomide is debatable, in
      the light of recent publications about venous and arterial thromboses observed
      with this treatment.

PMID- 14653065
TI  - [Gene expression profile changes in human multiple myeloma].
AB  - OBJECTIVE: To determine the difference in gene expression between human multiple
      myeloma (MM) and normal bone marrow. METHODS: cDNA chip was used to detect the
      mRNA of mononuclear cell from 10 untreated MM patients and 10 cases of normal
      bone marrow. RESULTS: Of the 2,048 genes, we found 566 different expression
      genes, of which the expression of 237 genes was higher and 329 lower in MM than
      in the normal bone marrow. CONCLUSION: Many genes may be involved in the
      pathogenesis of MM. cDNA chip technology is an effective tool in the study of
      tumor related genes.

PMID- 14653066
TI  - [A case of 5 consecutive hydatidiform moles].

PMID- 14653067
TI  - [Expression of E-cadherin gene protein in oral verrucous carcinoma].
AB  - OBJECTIVE: To determine the relationship between E-cadherin over-expression and
      progression in oral verrucous carcinoma. METHODS: Immunohistochemistry assay was
      performed on 12 cases of oral verrucous carcinoma (VC) and 20 cases of oral
      squamous epithelial cells carcinoma (SCC) using monoclonal antibody against E
      cadherin gene protein. RESULTS: The E-cadherin positive expression in VC (83.3%)
      was significantly higher than that in the poorly differentiated SCC(37.5%; P <
      0.05), but the negative expression of E-cadherin in VC was between the well
      differentiated squamous cell carcinoma and the poorly differentiated squamous
      cell carcinoma. CONCLUSION: E-cadherin over-expression plays an important role in
      oral verrucous carcinoma.

PMID- 14653068
TI  - [Cloning and sequence of human hepatocyte DNA synthetic stimulated factor cDNA].
AB  - OBJECTIVE: To clarify the nature of human hepatocyte DNA synthetic stimulated
      factor (HDSSF) and to lay a foundation for its gene cloning and expression.
      METHODS: We amplified the target gene fragment by degenerating PCR, labelled the
      fragment as a probe to screen human fetal liver cDNA library, and then analyzed
      the HDSSF gene sequence. RESULTS: A 600 base pair fragment was obtained and
      labelled successfully with DIG. Human HDSSF sequence was determined by screening
      the library and gene sequencing. Its cDNA chain was composed of 748 base pairs
      including 594 base pair open read-code frame and 5' and 3' terminal noncode
      district sequence. CONCLUSION: By screening cDNA library, the HDSSF gene cloning
      has been gained successfully. HDSSF should be a new hepatocyte growth substance
      which consists of 198 amino acid residues.

PMID- 14653069
TI  - [Expression of matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinases in the hepatocellular carcinomas].
AB  - OBJECTIVE: To explore the expression and clinical prognostic significance of
      matrix metalloproteinase-2 mRNA (MMP-2 mRNA), tissue inhibitor of matrix
      metalloproteinase-2 mRNA (TIMP-2 mRNA), matrix metalloproteinase-2 protein (MMP
      2), matrix metalloproteinase-9 protein (MMP-9), tissue inhibitor of matrix
      metalloproteinase-1 protein (TIMP-1), and tissue inhibitor of matrix
      metalloproteinase-2 protein (TIMP-2) in the hepatocellular carcinomas (HCCs).
      METHODS: Fifty-six specimens of HCCs from 56 patients, who were followed-up, were
      investigated by in situ hybridization with specific probes for MMP-2, TIMP-2, and
      by immunohistochemistry with anti-MMP-2, MMP-9 and anti-TIMP-1, TIMP-2 monoclonal
      antibody. We analyzed the data with chi-square test, spearmans correlation
      analysis, monovariate Kaplan-Meier plot and multivariate Cox regression analysis.
      RESULTS: 1. The positive expression of MMP-2mRNA, TIMP-2mRNA, MMP-2 protein, MMP
      9 protein, TIMP-1 protein and TIMP-2 protein in the 56 HCCs cases were 48
      (85.7%), 35 (62.5%), 44 (78.6%), 41 (73.2%), 30 (53.6%), and 38 (68%),
      respectively. 2. We found over-expression of MMP-2 mRNA, MMP-2 protein, and MMP-9
      protein, but low expression of TIMP-1 protein in the 56 cases of HCCs (P < 0.01,
      P < 0.05). 3. There was a positive association between TIMP-2mRNA and TIMP-2
      protein expression, and between MMP-2 mRNA and MMP-2 protein in HCCs,
      respectively (r = 0.316, P < 0.05; r = 0.356, P < 0.05). 4. Over-expression of
      MMP-2 mRNA was positively correlated to the tumor size and TNM classification (r
      = 0.441, P < 0.001; r = 0.340, P < 0.05), and MMP-9 protein was related to
      shortened survival (P < 0.05). 5. In both monovariate Kaplan-Meir plot and
      multivariate Cox regression analysis, the expression of MMP-2 protein and MMP-9
      protein were linked to unfavorable prognosis. These results were further
      confirmed by multivariate analysis in which MMP-2 protein and MMP-9 protein
      emerged as independent prognostic factors for poor survival regardless of the
      age, tumor size, tumor grades, TNM classification and expression of MMP-2mRNA,
      TIMP-2mRNA, TIMP-1 protein and TIMP-2 protein. The hazard ratios of expression of
      MMP-2 protein and MMP-9 protein were 3.875 and 4.528, respectively. CONCLUSION:
      The over-expression of MMP-2mRNA, MMP-2 protein and MMP-9 protein and the
      imbalance between MMP-2 and TIMP-2 play pivotal roles in the degradation of
      excellular matrix of HCCs. MMP-2 and MMP-9 immunoreactive protein have been
      closely related to a shortened survival independent of major prognostic
      indicators in the primary HCC and increase the risk of the patients after the
      operation.

PMID- 14653070
TI  - [TLR4 mRNA expression and liver injury in LPS-induced mouse].
AB  - OBJECTIVE: To determine the relationship between Toll-like receptor 4 (TLR4) mRNA
      expression and liver injury induced by lipopolysaccharide (LPS). METHODS: Balb/c
      mice were sacrificed at the indicated time points after the intra-peritoneal LPS.
      The livers were stained with hematoxylin and erosin for histopathologic analysis.
      Simultaneously, the expression of TLR4mRNA was detected by RT-PCR. RESULTS: A
      large number of inflammatory cells infiltrated into the portal areas and focal
      hepatocellular necrosis occurred 24 h after the intra-peritoneal LPS. The
      expression of TLR4mRNA in the liver was significantly depressed at 6 h and 12 h
      after the intra-peritoneal LPS, but recruited at 24 h. CONCLUSION: The signal
      transduction molecule TLR4 plays an important role in LPS-induced liver injury.

PMID- 14653071
TI  - [Construction and sequencing of recombinant plasmid pcDNA3/GRA1 from Toxoplasma
      gondii].
AB  - OBJECTIVE: To construct a mammalian expression plasmid pcDNA3/GRA1 to express
      dense granules antigen-1 (GRA1) of Toxoplasma gondii, and to lay a foundation for
      further studying the protective immunity of pcDNA3/GRA1 as a DNA vaccine.
      METHODS: The GRA1 opening reading frame (ORF) was amplified with two specific
      primers. The ORF and plasmid pcDNA3 were digested with EcoR I and Xho I
      respectively and the ORF was ligated into the pcDNA3 at polylinker. The
      recombinant vector pcDNA3/GRA1 was characterized by PCR, restriction enzyme
      digestion, and sequencing analysis. RESULTS: The expected ORF, 573 bp long, was
      amplified by PCR, and inserted into plasmid pcDNA3. PCR, restriction enzyme
      digestion and sequencing analysis showed that pcDNA3/GRA1 contained GRA1 ORF with
      the right orientation. CONCLUSION: The mammalian expression vector pcDNA3/GRA1 is
      successfully constructed.

PMID- 14653072
TI  - [Effect of ligustrazine on the expression of Bcl-2 protein and apoptosis in
      rabbit articular chondrocytes in monolayer culture].
AB  - OBJECTIVE: To determine the effect of ligustrazine on the expression of Bcl-2
      protein and apoptosis in rabbit articular chondrocytes in monolayer culture.
      METHODS: We separated chondrocytes from the rabbit articular cartilage and
      cultured them in vitro. We divided them into 2 groups. One group was added the
      injective ligustrazine hydrochloride(LH), and the other was added the same
      quantity of culture medium as the comparison. The expression of Bcl-2 in every
      group was examined with immunohistocytochemistry technique, and the apoptosis was
      observed with TUNEL. RESULTS: The two groups both expressed Bcl-2 protein, but
      the expression in the LH group was significantly higher than that in the
      comparison group (P < 0.01). The two groups both had apoptosis, the rate of which
      in the LH group was significantly lower than that in the comparison group (P <
      0.01). CONCLUSION: Ligustrazine may repair the cartilaginous lesion.

PMID- 14653073
TI  - [Gene expression of MMP1 and TIMP1 in lung cancer detected with a cDNA microarray
      technique].
AB  - OBJECTIVE: To investigate the gene expression of matrix metalloproteinases 1
      (MMP1) and tissue inhibitors of matrix metalloprotainases 1(TIMP1) in squmas cell
      lung cancer and adenocarcinoma. METHODS: Gene expression profile cDNA microarray
      egntaining 4,096 genes was used to identify differentially expressed genes in
      squmas cell lung cancer and adenocarcinoma, and to analyze the gene expression of
      MMP1 and TIMP1. RESULTS: Gene MMP1 and TIMP1 were differentially expressed in
      both squmas cell lung cancer and adenocarcinoma, and both of them were up
      regulated. CONCLUSION: MMP1 and TIMP1 may be important molecular markers of
      squmas cell lung cancer and adenocarcinoma.

PMID- 14653074
TI  - [Characteristics of Bcl-2 and Bax expressions in rat brain after experimental
      intracerebral hemorrhage and intervention of naoyian granule].
AB  - OBJECTIVE: To investigate the characteristics of Bcl-2 and Bax expressions in rat
      brain after experimental intracerebral hemorrhagic (ICH), and to determine the
      protective mechanisms of the Traditional Chinese medicine complex, naoyian
      granule (NYA). METHODS: ICH models were induced according to Rosenbergs method.
      The rats were divided into the model group, the NYA-treatment group and the sham
      group. Bcl-2 and Bax expressions in the rat brain after ICH were detected by
      immunohistochemistry method. RESULTS: Bax expressed in the hemorrhagic core, and
      the immunoreactive neurons were seriously injuried and the shape varied. Bcl-2
      expressed in the penumbra with the normal shape of the immunoreactive neurons.
      Both Bax and Bcl-2 expressed simultaneously in the marginal region of the
      cerebral hemorrhagic core. Bcl-2 expression in the rat brain reached the peak at
      the 2nd day and maintained at a relatively high level until the 7th day, and NYA
      could increase it. Bax expression peaked at the 1st day, and NYA could down
      regulate it. CONCLUSION: The expressions of Bcl-2 and Bax after the cerebral
      hemorrhage are related to the degree of injury, the time, and the location of the
      brain tissues. NYA can up-regulate the Bcl-2 expression and down-regulate the Bax
      expression, which may be one of its neuroprotective mechanisms.

PMID- 14653076
TI  - [A case of successful treatment in interrupted aortic arch].

PMID- 14653075
TI  - [Expression of PTEN and p27 proteins in non-Hodgkin's lymphoma].
AB  - OBJECTIVE: To investigate the effect of the expression of phosphatase and tensin
      homolog deleted on chromosome ten (PTEN) and p27 proteins in non-Hodgkin's
      lymphoma (NHL). METHODS: The expressions of PTEN and p27 proteins were detected
      with immunohistochemical technique in 77 cases of NHL. RESULTS: In NHL, the
      positive rates of PTEN and p27 protein were 90.9% (70/77) and 51.9% (40/77),
      respectively. The positive strength of PTEN protein was positively correlated to
      that of p27 protein (r = 0.6841, P < 0.01). The expression intensity of PTEN and
      p27 proteins in the low grade group was all higher than that in the high grade
      group. The expression intensity of PTEN and p27 proteins in B NHL showed no
      significant difference with that of T NHL. CONCLUSION: The decrease of p27
      protein expression caused by the deletion and descent of PTEN protein expression
      cannot effectively play the anti-oncogene role in negative regulation of the cell
      cycle, which makes the tumor cells more malignant.

PMID- 14653077
TI  - [Clinical analysis of 282 patients with non-Hodgkin's lymphoma].
AB  - OBJECTIVE: To analyze the classification, stage and prognosis of non-Hodgkin's
      lymphoma (NHL). METHODS: Two hundred eighty two patients with NHL were
      retrospectively reviewed. RESULTS: The complete remission (CR) rate and 5-year
      survival rate of B-cell NHL were higher than those of T-cell NHL(P < 0.05). There
      were significant differences in CR rate and 5-year survival rate among the low
      grade, the intermediate-grade and the high-grade NHL(P < 0.05). The CR rate and 5
      year survival rate of patients who were treated by the scheme of doxorubicin,
      cyclophosphamide, vincristine and prednisone (CHOP) were higher than those
      treated by the scheme of cyclophosphamide, vincristine, prednisone and etoposide
      (COP + VP16) (P < 0.05). CONCLUSION: Rational classification and staging play an
      important role in the prognosis of NHL. CHOP-based scheme may be regarded as the
      first choice and the standard scheme of treatment.

PMID- 14653078
TI  - [Purification of human MMP-1 fusion protein and clinical detection of MMP-1 by
      its polyclonal antibody].
AB  - OBJECTIVES: To obtain the fusion protein of MMP-1 and the rabbit-anti-human
      matrix metalloproteinase-1(MMP-1) polyclonal antibody, and to detect the serum
      MMP-1 in patients by this polyclonal antibody. METHODS: The fusion protein was
      purified by affinity chromatography. Two rabbits were immunized with the purified
      fusion protein, and the immune sera of rabbits were collected. Antibodies (IgG)
      obtained from the immune sera were purified by ammonium sulfate fractionation,
      and the indirect sandwich enzyme immunoassay was used to detect the serum MMP-1
      in 24 samples of patients with chronic liver disease or cirrhosis and in 12
      normal sera as controls. RESULTS: The purified MMP-1 fusion protein was
      successfully obtained; the purified specific polyclonal antibodies of rabbit-anti
      human MMP-1 were also obtained from the immune sera of the rabbits, and could
      respond to human MMP-1. Compared with the normal controls, the OD value of serum
      MMP-1 significantly increased in patients with chronic hepatitis or liver
      cirrhosis (P < 0.01). CONCLUSION: The rabbit-anti-human MMP-1 polyclonal antibody
      may be used in the diagnosis of initial stage of hepatic fibrosis.

PMID- 14653079
TI  - [Experimental study of mouse infected with human cytomegalovirus AD169 strain].
AB  - OBJECTIVE: To determine the sensitivity of mouse to human cytomegalovirus AD169
      strain (HCMV AD169) infection and to establish a stable animal model for
      developmental disorders. METHODS: Forty kunmin mice were divided into two groups
      randomly: the virus inoculated group and the control group. After 7, 15, 30, and
      60 days, the mice's brain development was observed by pathological techniques.
      HCMV antigen was detected by immunohistochemical method and HCMV DNA was analyzed
      by polymerase chain reaction (PCR). RESULTS: The extensive pathological damages
      and developmental disorders in the brain tissues of infected mice were observed.
      Meanwhile, the viral antigen and viral DNA were also demonstrated in the brain
      tissues of HCMV infected mice. CONCLUSION: HCMV can cause brain developmental
      disorders in mice, which provides a rationale for understanding the mechanism of
      congenital abnormality by HCMV infection.

PMID- 14653080
TI  - [Protective effects of shenmai injection on DPPH free radical-induced injuries in
      isolated hearts in rabbits].
AB  - OBJECTIVE: To examine the protective effects of shenmai injection (SM) on DPPH
      free radical-induced myocardial injury in isolated hearts in rabbits. METHODS:
      The isolated rabbit hearts were perfused in a Langendorff model. The left
      ventricular pressure (LVP), the first derivative of LVP (+dp/dtmax), left
      ventricular end-diastolic pressure (LVEDP) and heart rate(HR) were recorded.
      Coronary flow (CF) and creatine Kinase (CK) of coronary issue were measured.
      RESULTS: Perfusion with DPPH (0.25 mumol/L) for 5 min caused a significant
      impairment of cardiac function, as shown by a decrease in LVP and +dp/dtmax and
      an increase in LVEDP as well as the increased release of CK. Pretreatment with
      shenmai injection (1:320) for 10 min significantly improved the cardiac function
      and decreased the release of CK. CONCLUSION: Shenmai injection protects against
      the myocardial injury induced by free radical (DPPH) in isolated rabbit hearts.

PMID- 14653081
TI  - [Effects of nitroglycerin on plasma calcitonin gene-related peptide and
      endothelin in congestive heart failure].
AB  - OBJECTIVE: To investigate the plasma calcitonin gene-related peptide (CGRP) and
      endothelin (ET) levels and the effects of nitroglycerin on CGRP and ET in
      congestive heart failure (CHF), and to make clear the mechanism of nitroglycerin
      in vasodilation and cardiac protection. METHODS: The fast blood samples were
      taken from the peripheral vein of 40 volunteers and 40 CHF patients to estimate
      the basal level of CGRP and ET. Infusion of nitroglycerin of 25 to 50
      micrograms/min started in the forearm vein of CHF patients. Blood samples were
      taken at the end of the 1 hour infusion and (12 +/- 2) days of nitroglycerin
      treatment. Plasma concentrations of CGRP and ET were measured by
      radioimmunoassay. RESULTS: In patients with CHF before the treatment, the plasma
      concentration of CGRP was significantly lower than that in the controls (P <
      0.001), but the concentration of ET significantly higher than that in the
      controls (P < 0.001). During the nitroglycerin treatment, the plasma
      concentration of CGRP significantly increased (P < 0.001), whereas the
      concentration of ET significantly decreased (P < 0.01). The mean arterial
      pressure significantly decreased (P < 0.001). CONCLUSION: Nitroglycerin can
      increase the peripheral plasma CGRP level and decrease the concentration of ET
      when treating CHF. Intravenous nitroglycerin may be beneficial to the improvement
      of abnormal haemodynamics and neurohormonal derangement.

PMID- 14653082
TI  - [AT1 receptor autoantibodies and essential hypertension].
AB  - OBJECTIVE: To observe the relationship between AT1 receptor autoantibodies and
      clinical features in essential hypertension, and to compare the therapeutic
      effect of losartan between the positive and the negative group. METHODS: Clinical
      data were collected in patients with essential hypertension (n = 123). AT1
      receptor autoantibodies were checked. Twenty-four patients from either AT1
      positive or AT1-negative group were treated with losartan for 12 weeks. RESULTS:
      The average age in the positive group was significantly higher than that of the
      negative one (P = 0.023). Logistic regression analysis indicated that age was an
      independant risk factor of AT1 receptor autoantibody. Antihypertensive efficiency
      of losartan showed no obvious difference between the two groups. CONCLUSION:
      Positive response of AT1 receptor autoantibody is related only to age. Anti
      hypertensive therapy with losartan in the positive group shows no advantage over
      the negative one, indicating that AT1 receptor autoantibodies possibly have no
      vascular activity in vivo.

PMID- 14653083
TI  - [Two cases of diuretic abuse].

PMID- 14653084
TI  - [Effects of different doses of esmolol on cardiovascular responses to tracheal
      extubation].
AB  - OBJECTIVE: To observe the effects of different doses of esmolol on cardiovascular
      responses to tracheal extubation. METHODS: We randomly divided 175 patients
      undergoing elective surgery into 5 groups. Before the tracheal extubation,
      patients received 10 ml saline (group A), esmolol 0.5 mg/kg (group B), 1.0 mg/kg
      (group C), 1.5 mg/kg (group D) and 2.0 mg/kg (group E), respectively, and then
      the trachea was extubated 2 min later. Systolic blood pressure (SBP), diastolic
      blood pressure (DBP) and heart rate (HR) were recorded at premedication, tracheal
      extubation, and 1, 3, 5, 10 min after the tracheal extubation. Rate-pressure
      product was derived from SBP x HR. RESULTS: Compared with those at premedication,
      the SBP, DBP, HR, and RPP of the patients in Group A increased significantly at
      the tracheal extubation and 1 min after the tracheal extubation (P < 0.01). The
      DBP, HR, and RPP of patients in Group B were significantly higher at the tracheal
      extubation (P < 0.01). The SBP, HR and RPP of patients in Group B decreased
      significantly at the tracheal extubation and 1 min after the tracheal extubation
      compared with those in Group A (P < 0.01). The SBP, DBP, HR and RPP of patients
      in Group C, D and E decreased significantly at the tracheal extubation compared
      with those in group A and B (P < 0.05); as well as SBP, HR, RPP of patients in
      Group C, D, E at 1 min after tracheal extubation compared with those of patients
      in group A. SBP in Group C, D; HR in Group D, E; RPP in Group C, D, E decreased
      significantly at 3 min after the tracheal extubation compared with those in Group
      A(P < 0.05). Compared with premedication, HR, RPP in Group D decreased
      significantly at 3-10 min after the tracheal extubation and in group E at
      tracheal extubation, 1-10 min after the tracheal extubation (P < 0.05), but three
      patients in group E had a bradycardia after receiving esmolol. CONCLUSION:
      Esmolol of 1.5 mg/kg may not only control cardiovascular responses more
      effectively to the tracheal extubation, but also has no side-effects.

PMID- 14653085
TI  - [Impact of non-target gene mutations and reduced permeability of outer membrane
      on quinolone resistance and multiple antibiotic resistance in Escherichia coli].
AB  - OBJECTIVE: To investigate the impact of non-target gene mutations and reduced
      permeability of the outer membrane on quinolone resistance and multiple
      antibiotic resistance (mar) in Escherichia coli. METHODS: Several high-level
      quinolone resistant isolates whose strains were accompanied by concurrent
      resistant to several antibiotics were selected. The PCR products of marOR region
      were sequenced to detect the possible gene changes and then the strains' outer
      membrane proteins (Omps) were extracted to analyze on the constitutive profiles.
      RESULTS: We found two site mutations in R410 isolate: 1,870(T-->C, Val-->Ala) and
      1,879(A-->C, terminator-->Ser). The OmpF deficiency was found in all 3 resistant
      strains. CONCLUSION: The increased expression of MarA induced by gene mutations
      in marOR and the constitutive profile changes of the Omps (OmpF deficient
      strains) may play some role in the quinolone resistance and multiple antibiotic
      resistance of Escherichia coli.

PMID- 14653086
TI  - [Alteration of homocysteine before and after hemodialysis in chronic hemodialysis
      patients].
AB  - OBJECTIVE: To determine the plasma hemocysteine (Hcy) concentration in chronic
      hemodialysis patients and controls, and the relation between chronic hemodialysis
      and the plasma total Hcy level in chronic hemodialysis patients. METHODS: Using
      HPLC-FLD method, the plasma total Hcy concentration was determined in 11 patients
      with chronic hemodialysis and 30 healthy volunteers. RESULTS: The plasma total
      Hcy level in chronic hemodialysis was significantly higher than that in the
      controls (13.54 +/- 4.49 mumol/L) (P < 0.01). The plasma total Hcy level after
      the hemodialysis (21.30 +/- 10.81 mumol/L) was lower than before the hemodialysis
      (29.53 +/- 13.59 mumol/L) (P < 0.01). CONCLUSION: The plasma total Hcy level in
      chronic hemodialysis patients was higher than that in the controls. Hemodialysis
      can clean the plasma Hcy in chronic hemodialysis patients, but it can not
      decrease it to the normal level.

PMID- 14653087
TI  - [Examination of urogenital tract microorganism infection and antibiotic
      susceptibility test].
AB  - OBJECTIVE: To isolate bacteria, mycoplasma and chlamydia from the urogenital
      tract, and to determine their antibiotic susceptibility. METHODS: Bacteria,
      mycoplasma and chlamydia were isolated from the urogenital tract secretion by
      artifical culture, and their antibiotic susceptibility was detected by disk
      diffusion. RESULTS: The common microorganisms were S. epidermidis and
      corynebacberium, and the minority microorganisms were G- bacteria or E. coli.
      Bacteria were susceptible to amikacin, cephazolin V, rifampin, gentamycin, and
      docycyclin. CONCLUSION: S. epidermidis and corynebacterium are important
      pathogens of the urogenital tract infection. Disk susceptibility test can be used
      to screen the susceptible antibiotic.

PMID- 14653088
TI  - [Characteristics of bacteriology and drug sensitivity in patients with COPD
      combined with pneumonia].
AB  - OBJECTIVE: To investigate the characteristics of bacteriology and the drug
      resistance in the patients with chronic obstructive disease (COPD) combined with
      pneumonia at our respiratory intensive care unit(RICU) in 2001. METHODS: The
      sputum of 543 patients with COPD combined with pneumonia was collected with a
      regular method, the bacteria were cultured, and then the drug sensitivity was
      analyzed with K-B method. RESULTS: There were 181 positive samples in the 543
      patients with the positive rate 33.9%. The main bacteria in the G- bacillus were
      Pseudomonas (21.55%), Haemophilus influenza (14.36%), Enteric bacilli (13.26%),
      and Klebsiella (11.60%) which were sensitive to impipenem, amikacin, and
      ceftazidime. The main bacteria in G+ bacteria were Staphylococcus aureus (7.18%)
      and Staphylococcus epidermindis (4.42%) which were sensitive to vancomycin,
      imipenem, ceftazidime, and amikacin. CONCLUSION: The bacteria in the patients
      with COPD combined with pneumonia at RICU of the hospital in 2001 are mainly made
      up of G- bacillus and secondarily of G+ bacteria which are sensitive to imipenem,
      amikacin, and ceftazidime. The G+ bacteria are highly sensitive to vancomycin.

PMID- 14653089
TI  - [Clinical value comparison between chemiluminescent immunoassay and
      immunoradiometric assay in detecting TSH in serum].
AB  - OBJECTIVE: To compare the clinical value between chemiluminescent immunoassay
      (CLIA) and immunoradiometric assay (IRMA) in detecting TSH in patients with
      hyperthyroidism and hypothyroidism. METHODS: The TSH levels in serums were
      detected by CLIA and IRMA in 112 normal persons, 120 hyperthyroidism patients and
      58 hypothyroidism patients. RESULTS: CLIA was significantly correlated with IRMA
      (r = 0.98, P < 0.01). CLIA had higher coincidence rate than IRMA in the diagnosis
      of hyperthyroidism and hypothyroidism, and CLIA was more accurate and repetitive
      than IRMA. CONCLUSION: CLIA is more valuable than IRMA in diagnosing both
      hyperthyroidism and hypothyroidism.

PMID- 14653090
TI  - [Diagnostic value of serum-ascites albumin gradient].
AB  - OBJECTIVE: To evaluate the diagnostic value and efficacy of the serum-ascites
      albumin gradient (SAAG). METHODS: One hundred and thirty six patients with
      ascites fluid were divided into 5 groups: cirrhosis group (Group A, 42 cases),
      hepatocellular carcinoma group (Group B, 20 cases), spontaneous peritenitis group
      (Group C, 10 cases), tuberculous peritenitis group (Group D, 40 cases), and
      periteneal carcinomatosis group (Group E, 24 cases). Group A, B, and C all had
      portal hypertension. Ascites fluid from paracentesis was analyzed before the
      treatment. RESULTS: The ascites total protein (ATP) concentration in Group A, B,
      and C was less than 25 g/L but was more than 25 g/L in Group D and E. SAAG was
      more than 11 g/L in Group A, B, and C but less than 11 g/L in Group D and E.
      There was significant difference between the high SAAG group (> or = 11.0 g/L)
      and the low SAAG group (P < 0.01). PMN count was less than 250 x 10(6)/L in Group
      A, B, and E but more than 250 x 10(6)/L in Group C and D. There was no
      significant difference between Group C and D (P = 0.662). CONCLUSION: SAAG
      demonstrates that patients with ascites fluid possess the basis of portal
      hypertension. PMN count represents infective ascites. SAAG combined with PMN can
      effectively enhance the diagnostic value of ascites fluid tests. SAAG
      classification can be considered to be a novel standard in ascites fluid
      analysis.

PMID- 14653092
TI  - [Adsorbent effect of activated carbon on small molecular uremic toxin and its
      influence factors].
AB  - OBJECTIVE: To analyze the adsorbent effect of activated carbon on uremic toxin
      and its influence factors. METHODS: Uremic toxins (urea, creatinine and uric
      acid) were dissolved in the distilled water to obtain uremic toxic solution.
      Activated carbon was added to the solution, and the concentrations of uremic
      toxins were measured at different time spots. To determine the influence factors,
      some possible related materials, such as bile, amino acid, Ringer's, solution of
      glucose, HCl or NaOH respectively were added simultaneously. RESULTS: The
      concentrations of toxins in uremic toxic solution decreased 5 min after adding
      the activated carbon. The concentration of urea was the lowest at 30 min, but it
      increased after 50 min; while the concentrations of creatinine and uric acid
      reached the lowest level from 10 to 30 min after adding the activated carbon, and
      maintained at the same level after that. The bile, amino acid, electrolyte,
      glucose and pH value did not influence the adsorption of uric acid significantly,
      but they influenced the adsorption of urea and creatinine. Bile and amino acid
      influenced the concentration of urea remarkably, following glucose, NaOH and HCl.
      The effect of pH 2.0 solution on the creatinine concentration was the most
      significant, following glucose. CONCLUSION: Activated carbon has adsorptive
      effect on uremic toxins, but its adsorptive effect decreases as time goes on.
      Bile, glucose, amino acid, NaOH and HCl can affect the adsorptive effect of
      activated carbon on uremic toxins to some extent.

PMID- 14653093
TI  - [Expression of vascular endothelial growth factor in the peritoneal fluid and
      eutopic endometrium of patients with endometriosis].
AB  - OBJECTIVE: To investigate the significance of vascular endothelial growth factor
      (VEGF) on the etiology of endometriosis. METHODS: The level of VEGF in the
      peritoneal fluid from women with endometriosis (n = 19) and non-endometriosis (n
      = 21) was studied by ELISA. The expression of VEGF of eutopic endometrium
      collected from women with endometriosis (n = 15) and non-endometriosis (n = 12)
      was determined by relative quantity RT-PCR. RESULTS: The level of VEGF in the
      peritoneal fluid in the endometriosis was higher than that of the controls (P <
      0.05). Cyclic variation in VEGF concentration was seen in the peritoneal fluid
      from patients with endometriosis, and the VEGF concentration in the proliferative
      phase was significantly higher than that in the secretory phase (P < 0.05). No
      cyclic variation in VEGF was seen in the control group (P > 0.05). The expression
      of VEGF in the eutopic endometrium with endometriosis was significantly higher
      than that of the controls (P < 0.001). There was no significant difference
      between the proliferative and secretory phase in endometriosis (P > 0.05).
      CONCLUSION: The increase of VEGF in the peritoneal fluid and eutopic endometrium
      with endometriosis may be important to the occurrence and development of
      endometriosis.

PMID- 14653091
TI  - [Effect of L-EGCG on lipopolysaccharide-induced glomerular mesangial cell
      proliferation in rats].
AB  - OBJECTIVE: To determine the effect of L-epigallocatechins gallic acid ester (L
      EGCG) on glomerular mesangial cells (GMCs) proliferation, and to make clear the
      possible mechanism. METHODS: We investigated the effect of different doses of L
      EGCG on GMCs proliferation at 24 h, 48 h and 72 h respectively, and screened the
      best dosage and time point. GMCs were divided into 5 groups: control, L-EGCG
      group, LPS group, dexamethasone group, and L-EGCG plus dexamethasone group. At
      the end of the experiments, the cultured GMCs and its suspension were collected,
      the positive rate of proliferating cell nuclear antigen(PCNA) was taken count of
      by immunohistochemical assay, the rate of effective apoptosis of GMCs by terminal
      deoxynucleotidyl transferase mediated dUTP nick endlabeling (TUNEL) assay, and 
      OH, malonydialdehyde (MDA), superoxide dismutase (SOD) by biochemical assay.
      RESULTS: L-EGCG of 200 mg/L had the most strong inhibitory effect on GMCs at 48
      h. The levels of -OH, and MDA in the L-EGCG group was significantly lower than
      those in the LPS group (P < 0.01), while the level of SOD in the L-EGCG group was
      significantly higher than that in the LPS group (P < 0.01); the PCNA positive
      rate of GMCs in the L-EGCG group was significantly lower than that in the LPS
      group (P < 0.01), and the effective apoptosis of GMCs in the L-EGCG group were
      significantly higher than that in the LPS group (P < 0.01). The PCNA positive
      rate of GMCs was positively correlated with the level of -OH and MDA, while
      negatively correlated with the level of SOD. CONCLUSION: The suppressive effect
      of L-EGCG on the abnormal proliferation of GMCs might be that L-EGCG could weaken
      the suppressive effect of -OH on the SOD activity, decrease the accumulation of
      MDA, and increase the apoptosis of GMCs.

PMID- 14653094
TI  - [Ultrasonography via vaginal in diagnosing uterine anomalies].
AB  - OBJECTIVE: To investigate the clinical value of ultrasonography via vaginal in
      diagnosing uterine anomalies. METHODS: Patients in Infertility Clinic were
      scanned by endovaginal sonography. Hysterosalpingography (HSG) or hysteroscopy
      were performed in patients with uterine anomalies confirmed by ultrasonography.
      RESULTS: Twenty patients had uterine anomalies. Of them, 10 had double uterus, 4
      had bicornuate uterus, 3 arcuate uterus, 2 septate uterus, and the other 1
      unicornuate uterus. CONCLUSION: Uterine anomalies are easily detected by
      endovaginal sonography. The diagnosis of uterine anomalies is important in the
      treatment of infertility and in the prevalence of complications related to
      uterine anomalies such as abortion and premature labor in pregnancy.

PMID- 14653095
TI  - [Modification of silicone oil removal via limbus of corneal with aphakia].
AB  - OBJECTIVE: To introduce a simplified method to remove silicone oil via limbus of
      corneal after previous lensectomy-vitrectomy. METHODS: Fifty-one eyes received
      the modified procedures to eliminate silicone oil via one pars plana or limbus
      incision after previous lensectomy-vitrectomy. Local anesthesia was performed
      with 25G syringe needle through pars plana or corneal limbus infusion and super
      limbus incisions to eliminate silicone oil. RESULTS: All operations were
      primarily successful in eliminating silicone oil. The complications occurred in
      all the patients with the early low intraocular pressure, in 4 (4/51, 7.8%) eyes
      with retinal detachment, and in 2 (2/51, 3.9%) eyes with less bleeding at the
      point of puncture. The visual acuity was significantly improved after the
      procedure (P < 0.05) in patients with stable retinal reattachment. CONCLUSION:
      The procedure via one pars plana and limbus or limbus incision after previous
      lensectomy-vitrectomy is useful in removing the silicone oil tamponade in aphakic
      eyes because of its simplicity, good curative effect, and fewer complications.

PMID- 14653096
TI  - [Microsurgical treatment of trigeminel neurinomas with middle fossa extradural
      approach].
AB  - OBJECTIVE: To investigate the curative effect of microsurgical treatment of 15
      cases of trigeminel neurinomas with middle fossa extradural approach. METHODS:
      The clinical materials included the main clinical manifestations, preoperative CT
      and MRI features, operative techniques, and the outcome of 15 patients with
      trigeminel neurinomas were retrospectively analysed. RESULTS: Total resection was
      achieved in 12 of the 15 patients and subtotal resection in the other 3 patients.
      Ninety-four percent of the cranial nerve deficit was improved or unchanged, and
      only 6% of cranial nerve palsy worsened, postoperatively. None of the patients
      had new cranial nerve deficit after the operation, and there was not operative
      mortality. Twelve patients were followed up for 2-40 months and no recurrence of
      tumors was found. CONCLUSION: This approach may be ideal for removing big
      trigeminal neurinomas safely and radically and can decrease the postoperative
      complication and mortality.

PMID- 14653097
TI  - [Morphologic and hydrodynamic characteristics of bovine jugular venous conduit
      with valves].
AB  - OBJECTIVE: To determine the morphologic and hydrodynamic characteristics of
      bovine jugular venous conduit with valves. METHODS: Fresh bovine jugular veins
      with a retained native valve procured from a slaughterhouse were used as raw
      material to fabricate the valved conduits. The hydrodynamic performance of fresh
      and glutaraldehyde fixed bovine jugular vein conduits with valves was
      investigated in an experimental flow equipment that provided a constant pressure.
      The perfusion flow quantity through the conduits was measured under the antegrade
      (from the distal end to the proximal end) and retograde (from the proximal to the
      distal end) perfusion. The parameters of the valves in these bovine jugular
      venous conduits were also measured. RESULTS: There were 2-3 group valves in the
      bovine jugular venous conduit, with 3 or 2 valves in each group. The degrees of
      the leaflet development in different valves were different in the same conduit.
      The location of well-developed valves was interspersed. The anti-reflow ability
      of valves was positively correlated to the ratio between the leaflet height and
      valve sinus height (r = 0.709, P < 0.001). The percentage of retrograde and
      antegrade perfusion flow quantity after the glutaraldehyde treatment
      significantly increased than that before the glutaraldehyde treatment (P < 0.01).
      CONCLUSION: Part of the bovine jugular venous conduit has well-developed valves
      with strong ability against reflowing. Routine glutaraldehyde treatment obviously
      decreases the anti-reflow function of the conduits.

PMID- 14653098
TI  - [Effects of metoclopramide on intelligence and memory in patients with Tourette
      syndrome].
AB  - OBJECTIVE: To investigate the effects of metoclopramide on the intelligence and
      memory in patients with Tourette syndrome. METHODS: Before and after the 3 month
      treatment of metoclopramide, the intelligence of 25 children with Tourette
      syndrome was evaluated by the Wechsler intelligence scale fo children, and the
      memory by the Wechsler memory scale for children. RESULTS: The scores of
      intelligence in children treated by metoclopramide increased from 82.27 +/- 13.20
      to 90.53 +/- 15.50, with significant difference (P < 0.05). The scores of
      performance intelligence quotient increased from 84.13 +/- 10.60 to 92.40 +/-
      15.30 (P < 0.01). The scores of arithmetic subtle test for the support
      memory/attention, the block pattern subtle test for the support perception
      constitution factor, and the vision recognition subtle test for mean short-term
      memory increased from 8.20 +/- 2.70 to 10.20 +/- 3.21, 9.13 +/- 2.33 to 10.53 +/-
      2.94, and 6.07 +/- 4.56 to 8.40 +/- 3.56, respectively. CONCLUSION:
      Metoclopramide can improve the intelligence, short-term memory and attention in
      children with Tourette syndrome.

PMID- 14653099
TI  - [Physiotherapy with drugs for acute lymphadenitis of face and neck].
AB  - OBJECTIVE: To observe the clinical efficacy of acute lymphadenitis of face and
      neck treated by physiotherapy with drugs. METHODS: Ninety-six children with acute
      lymphodenitis of face and neck were randomly divided into 2 groups. Of the 96
      patients, 48 were treated by drugs as the control group, and the other 48 were
      treated by physiotherapy with drugs as the treatment group. Improvement of
      clinical symptoms and signs was compared after 3 days, and the treatment period
      was observed. RESULTS: Clinical symptom and sign of the treatment group were
      improved more than those of the controls (P < 0.01); the treatment period of the
      treatment group was shorter than that of the controls (P < 0.01). CONCLUSION: It
      is more effictive and costs less time to treat acute lymphadenitis of face and
      neck with physiotherapy with drugs.

PMID- 14653100
TI  - [A case of Wegener's granulomatosis].

PMID- 14653101
TI  - [Esophageal lead ECG in diagnosis of widen QRS tachycardia].

PMID- 14653102
TI  - [Evaluation of the lactate dehydrogenase and its isoenzymes in serum, pleural,
      and ascitic fluids].

PMID- 14653103
TI  - [Intravenous metastasis of primary hepatocarcinoma].

PMID- 14653104
TI  - [Fat and bone mineral density of middle-aged and young females].

PMID- 14653105
TI  - [Alteration of coupling ventricular premature beat cycles in electrocardiogram].

PMID- 14653106
TI  - [Detection of single-nucleotide polymorphisms in insulin receptor substrate-2
      gene 3'-untranslated region by denaturing high-performance liquid
      chromatography].
AB  - OBJECTIVE: To explore the use of denaturing high-performance liquid
      chromatography (DHPLC) in detecting single-nucleotide polymorphisms(SNPs) of
      insulin receptor substrate-2(IRS-2) gene 3'-untranslated region (3'-UTR).
      METHODS: We detected the SNPs and mutation of IRS-2 gene 3'-UTR sequence, with
      polymerase chain reaction (PCR), DHPLC, single-strand conformation polymorphism
      (SSCP), and DNA sequence analysis respectively in 30 Type 2 diabetic subjects and
      30 healthy controls. RESULTS: The SNPs of IRS-2 gene 3'-UTR in 4 patients with
      Type 2 diabetes mellitus were detected by PCR-DHPLC and were identified by DNA
      sequencing. CONCLUSION: DHPLC is a rapid and automated technology, which is
      simpler and more accurate for detecting longer fragment of DNA than SSCP. The
      present method lays a foundation for further studying the relationship between
      the mutation of IRS-2 gene 3'-UTR and Type 2 diabetes mellitus.

PMID- 14653107
TI  - [Competitive RT-PCR assay for quantification of GPI-PLD gene expression].
AB  - OBJECTIVE: To establish a competitive reverse transcription-polymerase chain
      reaction (RT-PCR) assay to quantify the expression of
      glycosylphosphatidylinositol specific phospholipase D (GPI-PLD) gene. METHODS: A
      competitive GPI-PLD cDNA fragment was constructed by site-directed mutagenesis by
      PCR method. The competitive cDNA fragment had the same primer binding sites as
      the target cDNA, but was 20 bp shorter in length. The competitive cDNA was
      transcripted into the competitive RNA in vitro as the internal standard. Then the
      competitive RNA was reversely transcripted and amplified together with total RNA
      extracted from K562 cells. The two amplified cDNA fragments could be
      distinguished by 10% polyacrylamide gel electrophoresis. The concentration of
      cellular GPI-PLD mRNA was derived from the ratio between the intensities of the
      bands corresponding to the amplified products. RESULTS: A 198 bp GPI-PLD
      competitive RNA was constructed and prepared. The competitive RNA could compete
      well with the target RNA in the RT-PCR reaction. The expression of GPI-PLD gene
      in K562 cells was (440 +/- 20) copies/ng. CONCLUSION: A competitive RT-PCR assay
      for the quantification of GPI-PLD gene expression may be established
      successfully. This method is highly sensitive, specific, and accurate.

PMID- 14653108
TI  - [Eight cases of ovarian mature cystic teratoma with malignant transformation].

PMID- 14653109
TI  - [Amplification of beta-catenin gene in the paraffin-embedded epidermal tissue].
AB  - OBJECTIVE: To establish a method of extracting DNA from the paraffin-embedded
      epidermal tissue and examine the amplification of beta-catenin gene by polymerase
      chain reaction (PCR) analysis. METHODS: Exon 3 of the beta-catenin gene was
      amplified by PCR in 14 paraffin-embedded Bowen's disease (BD) of various weight
      and years. RESULTS: The amplification of exon 3 of beta-catenin gene was
      successful in all the 10 mg and 20 mg samples, but not in the 5 mg samples. The
      amplification of exon 3 of beta-catenin gene was successful in 9 samples embedded
      within 10 years, and in only 2 of the 5 samples embedded more than 10 years.
      CONCLUSION: Epidermal tissue whose weight is 10 mg or more within 10 years of
      embedding can be used in the amplification of purpose gene by PCR.

PMID- 14653110
TI  - [Effects of lithium on the activity of ERK-1/2 signal pathway and expression of
      Bcl-2 family proteins in the central nervous system in vivo].
AB  - OBJECTIVE: To investigate the effects of chronic in vivo lithium administration
      on ERK-1/2 signal pathway and the expression of Bcl-2 family proteins, and to
      elucidate the molecular mechanisms underlying the therapeutic effects of lithium
      on the manic depression. METHODS: Forty male Wistar rats were evenly divided into
      2 groups. One group was treated with 2.4 g/kg of Li2CO3 for 4 weeks. The other
      group were given with normal chow. By the end of the 4th week, rat brains were
      removed immediately on decapitation and dissected on ice. The total proteins of
      rat brain hippocampus and frontal cortex were prepared. Levels of the prylated,
      active forms of MEK, ERK-1/2, RSK1 and CREB, and the expression levels of Bcl-2
      family were assayed by Western Blotting. RESULTS: Lithium increased the
      activities of MEK, ERK-1/2, RSK1, and CREB, up-regulated the expression of Bcl-2,
      and down-regulated the expression of Bax in rat brain hippocampus and frontal
      cortex. CONCLUSION: Chronic in vivo lithium administration activities ERK-1/2
      signal pathway and regulates the expression of Bcl-2 family proteins in the
      central nervous system, which may associate with the therapeutic effects of
      lithium in the treatment of manic depression.

PMID- 14653111
TI  - [Expression of secreted alkaline phosphatase in hepatocytes controlled by HCV
      IRES].
AB  - OBJECTIVE: To establish a cell model of secreted alkaline phosphatase (SEAP)
      controlled by HCV internal ribosome entry site (IRES). METHODS: The fragment of
      HCV 5' noncoding region (5' NCR) was amplified by polymerase chain reaction
      (PCR), and was immediately cloned the upstream of the SEAP gene of pSEAP2
      Control, an SEAP eukaryotic expression plasmid. With the liposome transfection
      technique, the resulting recombinant plasmid pdNCRSEAP was transfected into
      hepatocytes QSG7710, and the SEAP activity of cell culture media was monitored
      quantitatively by the chemiluminescent method. The regulatory effect of the HCV
      5' NCR on the SEAP expression was measured by the treatment of transfected cells
      with antisense oligodeoxynucleotide (ASODN) at 5 mumol and 10 mumol,
      respectively. RESULTS: The light emission intensity of pdNCRSEAP expression was
      76% that of pSEAP2-Control. The inhibition rates of pNCRSEAP luminescence
      intensity affected by ASODN of 5 mumol and 10 mumol were 29.2% and 44.6%,
      respectively, while ASODN had no significant effect on the pSEAP2-Control
      expression. CONCLUSION: The SEAP expression of pdNCRSEAP is controlled by HCV
      5'NCR. The cell model of drug evaluation targeted at HCV 5'NCR is successfully
      established and can be analyzed conveniently.

PMID- 14653112
TI  - [Construction of double-subunit co-expression eukaryotic vector of human
      interleukin 12].
AB  - OBJECTIVE: To construct the double-subunit co-expression plasmid P(+)/IL-12 to
      fulfill the gene therapy. METHODS: The full length cDNAs of P40 and P35, two
      subunits of hIL12, were amplified from the reverse transcription production of
      human embryo kidney using polymerase chain reaction (PCR) and respectively cloned
      into eukaryotic expression vector pcDNA3.1(+/-) to construct the single-subunit
      plasmids--P(+)/P40 and P(-)/P35. Then we linked cDNAs of P40 and P35 tandem and
      cloned them into pcDNA3.1(+) to get P(+)/IL-12 plasmid. The hIL-12 protein in
      supernate was detected with enzyme-linked immunoabsorbent assay (ELISA) after
      P(+)/IL-12 was transfected into HepG2 through liposome. RESULTS: The plasmid of
      P(+)/IL-12 was testified using enzyme cutting and sequencing analysis. ELISA
      showed that hIL-12 protein could be expressed after transfecting into HepG2.
      CONCLUSION: The successful construction of P(+)/IL-12 plasmid can not only
      simplify the operation steps but also mimic hIL-12 physiological expression style
      in the gene therapy, thus laying the foundation for the use of hIL-12 in the gene
      therapy.

PMID- 14653113
TI  - [Inhibitive effect of soybean isoflavone on prostate hyperplasia in rats].
AB  - OBJECTIVE: To explore the inhibitive effect of soybean isoflavone on benign
      prostatic hyperplasia in rats. METHODS: By subcutaneously injecting testosterone
      propionate to induce prostate hyperplasia in rats, the changes of prostate wet
      weight, prostatic index, morphological change, prostate-specific acid phosphatase
      (PAP), acid phosphatase in the control, the model, low, moderate, high dose of
      soybean isoflavone groups were observed. RESULTS: The ventral prostate wet
      weight, prostatic index, and PAP in the low, moderate, and high dose groups were
      significantly lower than those in the models (P < 0.05). The ventral prostate wet
      weight, prostatic index, and PAP in the moderate, and high dose groups were
      significantly lower than those in the low dose group (P < 0.05). CONCLUSION:
      Soybean isoflavone inhibits prostate hyperplasia and the increase of acid
      phosphatase and PAP in a dose-dependent manner in rats. Soybean isoflavone may
      serve as supplementary therapy and prevent benign prostatic hyperplasia.

PMID- 14653114
TI  - [Effect of Coptis Chinensis compound on the gene expression in transplanted tumor
      tissue in nasopharyngeal carcinoma cell line of CNE1 by cDNA microarray].
AB  - OBJECTIVE: To investigate the effect of Coptis Chinensis compound on the gene
      expression of transplanted tumor in nasopharyngeal carcinoma cell line of CNE1.
      METHODS: The cells were injected into Balb/C nude mice, and after the
      transplanted tumor was established, the nude mice with tumors were treated with
      Coptis chinensis compound. The nude mice were then killed, tumor tissues were
      isolated and the total RNA was extracted. Hybridization with a cDNA microarray
      was conducted using a probe of fluorescent-labeled cDNA mixture that was
      reversely transcribed from the RNA. The gene expression level was analyzed after
      scanning the fluorescent intensity by a laser scanner, and further confirmed by
      RT-PCR. RESULTS: After using Coptis Chinensis compound for 30 days, the size of
      transplanted tumors were remarkably reduced, and the inhibition rate of tumor
      growth was 29.5%. In the meantime, the expression of 147 genes in the tissue of
      implanted tumor treated with the compound altered: the expression of 102 genes
      was down-regulated, and that of 45 genes was up-regulated. Furthermore, the
      differential expression of 3 genes was verified by RT-PCR, MAD3 and H731 genes
      were up-regulated, and that of CHK1 was down-regulated. CONCLUSION: Coptis
      Chinensis compound can affect the gene expression in the tissue of implanted
      tumor, which implies that the inhibition of Coptis Chinensis compound on the
      growth of the implanted tumor with CNE1 cells in nude mice might be associated
      with the control of gene expression.

PMID- 14653115
TI  - [Effect of Citrus aurantium extract on L-type calcium currents in ventricular
      myocytes of single guinea pigs].
AB  - OBJECTIVE: To determine the effect of citrus aurantium extract (CAE) on L-type
      calcium currents (ICa-L) in ventricular myocytes of guinea pigs. METHODS: Single
      myocytes were dissociated by enzymatic dissociation method. The whole-cell patch
      clamp recording technique was used to record the change of calcium current after
      the administration of CAE. RESULTS: 1. CAE 4 x 10(-3), 2 x 10(-2), 4 x 10(-2),
      and 1 x 10(-1) g/ml increased the ICa-L by 15.89%, 29.01%, 52.03% and 59.76% (P <
      0.05), respectively. 2. CAE 2 x 10(-1) and 4 x 10(-1) g/ml decreased the ICa-L by
      16.61% and 30.87% (P < 0.05), respectively. CAE changed the ICa-L significantly,
      but did not change the shape of I-V curves. CONCLUSIONS: CAE 4 x 10(-3)-1 x 10(
      1) g/ml can increase the L-type calcium current in guinea pig ventricular
      myocytes significantly in a concentration-dependent manner, and promote the
      opening of calcium channel. CAE 2 x 10(-1)-4 x 10(-1) g/ml may inhibit the L-type
      calcium channels of ventricular myocytes, and depress the opening of calcium
      channel.

PMID- 14653116
TI  - [Effects of lithium chloride on the proliferation and apoptosis of K562 leukemia
      cells].
AB  - OBJECTIVE: To investigate the effects of lithium chloride on the proliferation
      and apoptosis of human leukemia cell line (K562). METHODS: The effects of lithium
      chloride on the proliferation of K562 leukemia cells were evaluated by liquid
      culture assay, MTT assay, and colony formation assay. The effects of lithium
      chloride on the apoptosis of K562 leukemia cell were verified by cellular
      morphology and the agarose gel electrophoresis of DNA fragments. RESULTS: 1. The
      proliferation of K562 leukemia cells was inhibited by lithium chloride (10-50
      mmol/L) in a dose-dependent manner. 2. With lithium chloride (30 mmol/L), the
      apoptosis cells could be observed in cellular morphology, and DNA ladder was also
      observed in agarose gel electrophoresis. CONCLUSION: Lithium chloride can inhibit
      the proliferation of K562 cells and cause the apoptosis of K562 cells.

PMID- 14653117
TI  - [Protective effect of Polygonum multiflorum thunb on the cerebral cholinergic
      neurofibers in rats].
AB  - OBJECTIVE: To observe the number and morphological changes of cholinergic
      neurofibers in rats under the destruction of kainic acid, and to investigate the
      protective effect and the mechanism of polygonum multiflorum thunb (PMT) on
      acetyl-chorine esterase (AChE) neurofibers. METHODS: Excitative neurotoxin kainic
      acid was injected into the basal forebrain, Meynert neucleus, medial septal
      neucleus and the Broca neucleus to establish the destruction model. Then the
      destructive experimental group was fed with PMT, and the histochemical method was
      used to display the changes of AChE fibers, the protection and activation of PMT.
      RESULTS: The number of projecting AChE fibers to the cortex and the hippocampus
      in PMT group was larger than that in the control group, and no morphological
      destruction was seen in the experimental group (P < 0.01). CONCLUSION: PMT has a
      protective effect on AchE projecting fibers in rats.

PMID- 14653118
TI  - [Nuclear factor-kappa B activity at the early stage of brain ischemia and
      reperfusion in mice].
AB  - OBJECTIVE: To observe the activity of nuclear factor-kappa B(NF-kappa B) during
      reperfusion after temporary brain ischemia and to evaluate its effect. METHODS:
      The brain ischemia-reperfusion(I/R) model of mice was established with ligating
      bilateral common carotid arteries and bleeding for 0.3 ml in the tail. Abnormal
      nervous symptoms (ANS) were recorded. Immunohistochemical technique was used to
      detect the activity of NF-kappa B subunit P65 and the inhibitory factor-kappa B
      alpha(I-kappa B alpha) in cerebral cortex during different periods of ischemia
      and reperfusion. Their mRNA expressions were also measured by RT-PCR. RESULTS: NF
      kappa B P65 activity significantly increased 30 minutes after the reperfusion,
      peaking at the 2nd hour, and remaining high within 24 hours (all P < 0.05). But
      the mRNA expression didn't change much; I-kappa B alpha and its mRNA expression
      began to decrease at 30 minutes after the reperfusion, peaking at the 2nd hour
      after the reperfusion (P < 0.05) and then gradually restored. Positive
      correlation was found between NF-kappa B P65 activity and ANS (P < 0.05), while
      negative correlation was shown among I-kappa B alpha, its mRNA, and ANS (P <
      0.05, respectively). CONCLUSION: Both activated NF-kappa B and decreased I-kappa
      B alpha exist in the neural tissues of mice at the early stage of brain ischemia
      reperfusion. The activated NF-kappa B may be involved in the ischemia-reperfusion
      injury.

PMID- 14653119
TI  - [A case of pulmonary alveolar microlithiasis].

PMID- 14653120
TI  - [Expression of ET-3 in hippocampal CA1 of ovariectomied mice after cerebral
      ischemia/reperfusion].
AB  - OBJECTIVE: To detect the expression of endothelins-3 (ET-3) immunoactivity in
      hippocampal CA1 of ovariectomied (OVX) mice after ischemia/reperfusion (IR), and
      to further explore the relationship between estrogen and ET-3. METHODS: Fifty
      four adult female mice were randomly divided into 3 groups. 1. IR group: the
      bilateral common carotid occlusion (BCCO) was carried out for 7 min on the 1st,
      3rd, 5th and 14th day of reperfusion. 2. OVX/IR group: firstly the ovariectomy
      was performed, and after a week, BCCO was carried out for 7 min on the 1st, 3rd,
      5th and 14th day of reperfusion (each time spot, n = 6). 3. sham-operated group
      (n = 6). RESULTS: Few ET-3 positive cells were diffusely distributed in the
      hippocampal CA1 region in the control group, whereas the expression of ET-3
      increased in the experimental groups. The number of ET-3 positive cells
      significantly increased in the OVX/IR group compared with that of the IR group 1
      d after the reperfusion (P < 0.01). It reached the maximum in both the OVX/IR and
      IR group on the 5th day of the reperfusion. CONCLUSION: Estrogen is involved in
      the regulation of ET-3 in the early stage of the reperfusion, and probably plays
      a protective role in the survival of neurons.

PMID- 14653121
TI  - [Clinical characteristics and genetic analysis of rare chromosome aberration in
      peripheral blood].
AB  - OBJECTIVE: To investigate the main clinical characteristics and genetic analysis
      of rare chromosome aberration in peripheral blood. METHODS: Peripheral blood
      cells were cultured for 72 hours with routine method and slids performed, and
      then the slide was read and mode analysis was carried out. The diagnostic
      standard of rare chromosomal aberation was: 1-2 abnormal kary types were found in
      every 30, 60, 200 mitotic phass. RESULTS: The main clinical characteristics of 52
      cases of individual chromosomal aberation in peripheral blood included: 1.
      spontaneous abortion; 2. abnormal sex development; 3. reproduction diseases; and
      4. morbid and deformity. CONCLUSION: Rare chromosomal aberation should be
      regarded as chromosomal diseases. Prenatal diagnosis is necessary for people with
      such chromosomal aberation in their reproductive actions.

PMID- 14653122
TI  - [Ambulatory pulse pressure and left ventricular hypertrophy in patients with
      essential hypertension].
AB  - OBJECTIVE: To evaluate the relationship between the left ventricular hypertrophy
      (LVH) and the ambulatory pulse pressure and aortic root dimension (AOD) in
      essential hypertensive patients. METHODS: We monitored the 24-hour ambulatory
      blood pressure and applied echocardiography in 107 essential hypertensive
      patients. Using the left ventricular mass index (LVMI) as an index in evaluating
      LVH, the patients were divided into 2 groups: 29 cases in the LVH group and 78 in
      the non-LVH group. RESULTS: The average levels of 24-hour pulse pressure, daytime
      pulse pressure, nighttime pulse pressure and AOD were significantly different
      between patients with LVH and without LVH (P < 0.05). Multiple stepwise
      regression analysis showed that the changes in nighttime pulse pressure and AOD
      were closely related to LVMI (P < 0.001). CONCLUSION: The pulse pressure and AOD
      are important factors leading to LVH in patients with essential hypertension.

PMID- 14653123
TI  - [Serum nitric oxide and D-dimer before and after administering antihypertensive
      drugs in essential hypertension].
AB  - OBJECTIVE: To investigate the relationship among serum nitric oxide, D-dimer,
      blood pressure, dangerous states and target organ damage in essential
      hypertension and to evaluate the effects of enalapril and terazosin. METHODS:
      Fifty-five patients were randomized into the enalapril group and terazosin group,
      each group receiving enalapril and terazosin respectively for 8 weeks. Serum
      nitric oxide and D-dimer were measured before and after the treatment. RESULTS:
      Serum nitric oxide was lower (P < 0.001) but D-dimer was higher (P < 0.01) in the
      hypertensions than those in the controls. Serum nitric oxide and D-dimer were
      related to different levels of blood pressure, dangerous states and target organ
      damage; Both enalapril and terazosin could reduce the level of blood pressure;
      Both could increase the serum nitric oxide (P < 0.001) and decrease the D-dimer(P
      < 0.01). CONCLUSION: Endothelial dysfunction and microthrombin can be found in
      the early stage of essential hypertension. Both enalapril and terazosin could
      improve the endothelial function and prothrombotic state by promoting the
      synthesis of nitric oxide.

PMID- 14653124
TI  - [Clinical value of cast post-core porcelain fused to metal crown in restorating
      residual root and crown of molars].
AB  - OBJECTIVE: To investigate the effect of cast post-core porcelain fused to metal
      crown on the restoration of residual root and crown of molars. METHODS: One
      hundred and sixty-four residual roots and crowns of molars were treated with root
      canal therapy and restored by cast core porcelain fused to metal crown. The
      restoration effect was assessed at the 3rd, 6th, 12th and 24th month. RESULTS:
      The strength of dental prosthesis retention, marginal fitness, and strength of
      crowns were satisfactory. The effective rate reached 95.12% during the 2 year
      follow-up. CONCLUSION: The cast post-core porcelain fused to metal crown is a
      better method in treating the residual root and crown of molars.

PMID- 14653125
TI  - [Expression of S100 in oral submucose fibrosis].
AB  - OBJECTIVE: To study the expression of S100 in oral submucose fibrosis(OSF).
      METHODS: Immunohistochemistry assay was performed on 10 cases of OSF, 10 cases of
      oral epithelial dysplasia (OED) and 8 cases of normal oral epithelium using
      monoclonal antibody against S100 protein. RESULTS: S100 did not express in the
      normal oral muscosal epithelium. The S100 positive nuclear staining was found in
      50% of the OSF and OED cases, which was significantly higher than that in the
      normal oral epithelium (P < 0.05). But the positive staining in the OSF and OED
      cases had no difference (P > 0.05). CONCLUSION: S100 expression is closely
      related to the development of OSF and OED. The positive staining expression in
      the OSF and OED cases is the same.

PMID- 14653126
TI  - [A short-term trial of Didanosine, stavudine, and nevirapine combination therapy
      for human immunodeficiency virus infection].

PMID- 14653127
TI  - [Surgical treatment of 92 cases of thoracic aortic aneurysms].
AB  - OBJECTIVE: To explore the timing of surgical treatment of thoracic aortic
      aneurysms. METHODS: The clinical data of 92 patients with thoracic aortic
      aneurysm who underwent surgical treatment in our department during the latest 10
      years were retrospectively reviewed. RESULTS: The overall operative mortality was
      13.04% (12/92) 30 days after the operation. Risk factors for the early mortality
      were the preoperative aneurysm breach, hypertension, important organ dysfunction
      and circulatory arrest during the operation, as well as the serious postoperative
      complications, such as arrhythmia, dysfunction or failure and infection of
      important organ, and so on (P < 0.05-0.01). CONCLUSION: The surgical treatment is
      an ideal way of treatment of thoracic aortic aneurysm. To choose appropriate
      timing and methods for the operation, to improve skills of the operation, to
      shorten the time of the operation, and to protect function of important organs
      contribute to the increase of the successful rate of the surgical treatment of
      thoracic aortic aneurysm and the decrease of the incident of postoperative
      complications.

PMID- 14653128
TI  - [ZEPHIR plate fixation in anterior surgery of the cervical spondylotic
      myelopathy].
AB  - OBJECTIVE: To evaluate the clinical outcome of ZEPHIR plate in treating cervical
      spondylotic myelopathy(CSM). METHODS: We retrospectively analyzed 18 patients
      undergoing anterior decompression fusion and internal fixation with ZEPHIR plate.
      Follow-up period ranged from 3 to 12 months (an average of 9 months). The bone
      graft fusion rate, rehabilitation of neurological deficits, and the complications
      of the hardware were observed. We assessed the clinical effect with JOA score.
      RESULTS: Rehabilitation of neurological deficits were observed in 16 patients,
      The JOA score after the operation significantly increased than before the
      operation. The fusion rate was 100%, the intervertebral height were maintained,
      and no complications related to the plate were found. CONCLUSION: ZEPHIR plate in
      the treatment of cervical spondylotic myelopathy may increase the fusion rate of
      the bone graft significantly with low incidence of complication.

PMID- 14653129
TI  - [Clinical observation of recombinant growth hormone therapy for liver cirrhosis
      with hypoproteinemia].
AB  - OBJECTIVE: To assess the effect of recombinant growth hormone (rhGH) therapy for
      liver cirrhosis patients with hypoproteinemia. METHODS: Fifteen patients with
      liver cirrhosis were treated with rhGH (4 U per day) for 7 days and 15 controls
      were given human albumin (10 g) for every other day (altogether 3 times). Albumin
      was measured one day before the treatment, and on day 1, 10, 14, and 28 after the
      treatment. RESULTS: After 7 days of rhGH administration, the albumin level of the
      patients was significantly higher and the function lasted longer than those of
      patients treated with human albumin (P < 0.05). CONCLUSION: Exogenous rhGH in
      treating hypoproteinemia in patients with liver cirrhosis is more effective than
      human albumin.

PMID- 14653130
TI  - [Effect of tianlong xifeng granule on gan-yang-hua-feng zheng in cerebral
      arteriosclerosis].
AB  - OBJECTIVE: To investigate the efficacy of Tianlong Xifeng granule (TXG) in the
      treatment of ceroarterosclerosis (CAS) with Gan-yang-hua-feng Zheng(GYHFZ).
      METHODS: Patients with CAS were randomly divided into 2 groups: 122 patients in
      the treatment group were given TXG, while 60 patients in the control group were
      treated with Ginkgo Biloba capsule. Clinical symptom, blood lipid and
      transcranial doppler ultrasound were observed before and after the treatment.
      RESULTS: The symptom, elasticity of the cerebral blood vessel, and the speed of
      blood flow were significantly improved in the treatment group, and the efficacy
      of the treatment group was superior to that of the control group. Blood lipid was
      effectively reduced, and no toxic and side effects were found in both groups.
      CONCLUSION: TXG has ideal therapeutic effect on CAS patients with GYHFZ.

PMID- 14653131
TI  - [Infective pathogens and drug resistance in burned patients].
AB  - OBJECTIVE: To find out the changes in the infective pathogens and their drug
      resistance in burned patients. METHODS: The patients were divided into two
      groups. The first group was from July 1991 to June 1996, and the second group was
      from July 1996 to June 2001. The bacteria of burned body surface and blood were
      cultured, and the bacteria and their drug sensitivity were analyzed. RESULTS:
      Gram-negative bacteria were the major bacteria in burn infection, among which
      Pseudomonas aeruginosa ranked the top. Staphylococcus aureous ranked the first
      among the Gram-positive bacteria, and the isolation rate of methicillin resistant
      Staphylococcus aureus increased; The isolation rate of Enterobacter cloacae
      (10.4%), Escherichia coli (8.3%), Klebsiella pneumoniae (7.3%), and fungus (4.2%)
      all rose. The antibiotic resistant strains of Pseudomonas aeruginosa and
      Staphylococcus aureous increased. CONCLUSION: The changes in pathogens of burn
      infection and bacterial drug resistance are related to the wide use of broad
      spectrum antibiotics such as cefazidime and imepenem, suggesting that dynamic
      observation of changes in pathogenic strains and sensitivity of bacteria to
      antibiotics are useful for clinical prevention and cure of burn infection.

PMID- 14653132
TI  - [A case of Kallmann syndrome].

PMID- 14653133
TI  - [Influential factors to therapeutic efficacy of uterine artery embolization in
      the treatment of uterine fibroids].
AB  - OBJECTIVE: To investigate the therapeutic efficacy of uterine artery embolization
      in the treatment of uterine fibroids and to analyse the influential factors to
      the therapeutic efficacy. METHODS: Thirty-two patients with symptomatic uterine
      myomas were treated by superselective catheterization and embolization of
      bilateral uterine arteries using PVA particles. Patients were followed for 6
      months after uterine artery embolization. Baseline symptoms and the volume of the
      fibroids were used as parameters to evaluate the therapeutic efficacy.
      Influential factors to therapeutic efficacy were analyzed. RESULTS: The clinical
      symptoms, especially heavy menstrual bleeding, were improved markedly. An average
      of 55.6% volume reduction of the fibroids was achieved during the 6 month follow
      up. The submucosal and intramural location of the myomas reduced more in the
      volume compared with that of the subserosal location. CONCLUSION: Selective
      uterine artery embolization is effective for uterine myoma. Influential factors
      to the therapeutic efficacy may include: postprocedural vascular reconstruction
      in the fibroid, location of the fibroid, hemodynamic status of the fibroid, and
      the mode of embolization (unilateral or bilateral).

PMID- 14653135
TI  - [Particle enhanced immunoturbidimetic assay of high sensitive C-reactive
      protein].
AB  - OBJECTIVE: To evaluate the particle enhanced immunoturbidimetic assay of high
      sensitive C-reactive protein by the automated chemistry analyzer (Hitachi 7170A).
      METHODS: The detection limit of quantification, measurement range, precision,
      interference and reference interval were assessed. RESULTS: The measurement range
      of the method was from 0.125 to 12.5 mg/L. The detection limitation was 0.115
      mg/L. The internal and external accuracy were 0.89% and 0.90% respectively. The
      reference range of the assay was from 0.20 mg/L to 2.60 mg/L. CONCLUSION: The
      particle enhanced immunoturbidimetic assay is sensitive and stable, and can be
      used in clinical diagnosis.

PMID- 14653134
TI  - [Etiology of infectious diseases in the central nervous system].
AB  - OBJECTIVE: To determine the etiological characteristics of infectious diseases in
      the central neural system (CNS). METHODS: The serum and cerebral spinal fluid of
      acute patients in the CNS were detected for virus-specific IgM, IgG and pathogens
      with enzyme-linked immunosorbent assay as well as traditional bacterial and
      fungal culture. RESULTS: Of the 823 patients, 126 (15.3%) patients were positive
      herpes simplex virus (HSV)-specific IgM and/or IgG, of which the maximum
      morbidity was under 10 years; 10(1.2%) were positive cytomegalovirus specific IgM
      and/or IgG; 8 (0.97%) were positive varicella-zoster virus specific IgM and/or
      IgG; 7 (0.85%) were diagnosed as tubercular meningitis; 6 (0.72%) as
      cryptocococes meningitis and 1 (0.12%) as meningococcic meningitis. CONCLUSION:
      Viruses, especially herpes simplex viruses are the common causative agents of
      infectious diseases of the CNS, in which mycobacterium tuberculosis and
      cryptocococcus neoformans are conspicuous.

PMID- 14653136
TI  - [Dry chemistry method for measuring serum urea and creatinine].
AB  - OBJECTIVE: To evaluate the dry chemistry method for measuring serum urea and
      creatinine. METHODS: Urea and Creatinine were measured by dry and wet chemistry
      methods respectively. The results and the relativity between the two methods were
      compared. RESULTS: The correlative factors were 0.996 and 0.995, respectively,
      implying fairly good comparability. The precision of the dry chemistry method was
      good, with the coefficient variation (CV) below 5%. With favorable accuracy, the
      recovery rate were 106.7% and 107.2%, respectively. CONCLUSION: Dry chemistry
      method is rapid and accurate for emergent testing of serum urea and creatinine.

PMID- 14653138
TI  - [Influence of rosiglitazone on the airway inflammation in guinea pigs with
      asthma].

PMID- 14653137
TI  - [Hysterosalpingography combined with hysteroscopy-laporoscopy in diagnosing
      female infertility].
AB  - OBJECTIVE: To evaluate hysterosalpingography (HSG) combined with hysteroscopy
      laparoscopy in diagnosing female infertility. METHODS: One hundred thirty three
      female infertile patients by clinical diagnosis were given HSG and hysteroscopy
      laparoscopy, and the results were retrospectively analyzed. RESULTS: The total
      diagnostic coincidence rate of the two methods in diagnosing uterus-cervix
      infertility was 80.2%, while the coincidence rate of the two methods in
      diagnosing tubal infertility was 89.7%. CONCLUSION: HSG combined with
      hysteroscopy-laparoscopy is an optimal method in diagnosing female infertility at
      present.

PMID- 14653139
TI  - [Expression of MMP-9 and CD34 in papillary thyroid carcinomas].

PMID- 14653140
TI  - [Mechanical ventilation of acute exacerbated chronic obstructive pulmonary
      disease with CO2 retention].

PMID- 14653141
TI  - [Analysis of cytogenetic features in the patients with chronic myeloid leukemia].

PMID- 14653142
TI  - [Dynamic observation of the arteriovenous fistula and the blood flow in patients
      undergoing hemodialysis].

PMID- 14653143
TI  - [Clinical evaluation of hypotonic and hypopressive intravenous pyelography].

PMID- 14653144
TI  - [Effects of isoket on hemodynamics during extubation and anesthesia emergency].

PMID- 14653145
TI  - [Basic up-right tilt table in diagnosing vasovagal syncope].

PMID- 14653146
TI  - Innate versus learned movements--a false dichotomy?
AB  - It is argued that the nervous systems of vertebrates are equipped with a "motor
      infrastructure," which enables them to perform the full extent of the motor
      repertoire characteristic of their particular species. In the human, it extends
      from the networks/circuits underlying locomotion and feeding to sound production
      in speech and arm-hand-finger coordination. Contrary to current opinion, these
      diverse motor patterns should be labeled as voluntary, because they can be
      recruited at will. Moreover, most, if not all, of the motor patterns available at
      birth are subject to maturation and are modified substantially through learning.
      We thus argue that the all-too-common distinction between learned and innate
      movements is based on a fundamental misconception about the neural control of the
      vertebrate motor system.

PMID- 14653147
TI  - Why and how are posture and movement coordinated?
AB  - In most motor acts, posture and movement must be coordinated in order to achieve
      the goal of the task. The focus of this chapter is on why and how this
      coordination takes place. First, the nature of posture is discussed. Two of its
      general functions are recognized; an antigravity role, and a role in interfacing
      the body with its environment such that perception and action can ensue. Next
      addressed is how posture is controlled centrally. Two models are presented and
      evaluated; a genetic and a hierarchical one. The latter has two levels; internal
      representation and execution. Finally, we consider how central control processes
      might achieve an effective coordination between posture and movement. Is a single
      central control process responsible for both movement and its associated posture?
      Alternatively, is there a dual coordinated control system: one for movement, and
      the other for posture? We provide evidence for the latter, in the form of a
      biomechanical analysis that features the use of eigenmovement approach.

PMID- 14653148
TI  - Motor coordination can be fully understood only by studying complex movements.
AB  - In this chapter, we use the sit-up to illustrate the complexity of coordination
      in movements that involve many muscles, joints, degrees of freedom, and high
      levels of muscle activity. Complex movements often involve the body axis. In
      addition to the intentional, focal part of any voluntary movement, complex
      movements also include "associated movements" that are not consciously
      controlled, but are necessary for the movement to succeed. Some associated
      movements serve a purpose, and others may not. During sitting up, the leg-lift is
      a purposive associated movement, whereas three-joint flexion is a non-purposive
      associated movement. The control of complex movements is also likely to be
      complex and, we argue, is hierarchically controlled. Associated movements may,
      themselves, be hierarchically organized and triggered by lower brain structures,
      local changes in neuronal excitability, and sensory feedback. Complex movements
      typically involve a high level of mobility. Because this mobility can lead to
      instability, anticipatory postural adjustments, a type of purposive associated
      movement, are commonly used to regulate posture. Thus, a number of important
      aspects of motor coordination can only be revealed by the study of complex
      movements.

PMID- 14653149
TI  - The emotional brain: neural correlates of cat sexual behavior and human male
      ejaculation.
AB  - The organization of virtually all basic survival mechanisms in the central
      nervous system (CNS) is within the most central regions of the mesencephalon and
      the rostrally adjoining diencephalon; in particular, the mesencephalic
      periaqueductal gray (PAG) and hypothalamus. The PAG sends specific pathways to
      the caudal brainstem where neurons are located that, in turn, control
      nociception, blood pressure, heart rate, and micturition. Via projections to the
      nucleus retroambiguus (NRA) in the most caudal part of the medulla, the PAG
      controls the intra-abdominal pressure associated with vocalization, vomiting, and
      parturition. In cats, the PAG also controls sexual posture via NRA projections to
      motoneurons in the lumbosacral cord. These NRA-lumbosacral motoneuronal pathways
      are almost nine times stronger in the estrous vs. non-estrous female cat. While
      neuronal activity in specific CNS pathways is now known to control sexual
      behavior in the cat, how is it organized in the human? PET-scan results on human
      ejaculation have revealed that the meso-diencephalic transition zone is
      particularly and strongly activated. This region includes the so-called ventral
      tegmental area that is also known as a "reward area." For example, it is also
      activated during a heroin rush. Other strongly activated structures during sexual
      activity include the cerebellum and lateral part of the corpus striatum. At the
      level of the cerebral cortex, areas in the prefrontal and parietal cortex are
      also activated, but exclusively on the right side. Further study of these
      structures should certainly lead to better insight into human sexual behavior and
      provide the possibility to improve sexual activity in those who suffer from
      problems in this area.

PMID- 14653150
TI  - Developmental changes in rhythmic spinal neuronal activity in the rat fetus.
AB  - In the developing rat spinal cord, formation and differentiation of the central
      pattern generator for locomotion occur during the prenatal period. Early on,
      excitatory synaptic transmission mediated by glycine receptors plays a leading
      role for rhythmogenesis, at a later stage, followed by glutamate-receptor
      mediated synaptic transmission becoming dominant. The maturation of inhibitory
      circuitry in the spinal cord, mediated largely by glycinergic synapses, is
      crucial for the generation of alternating activity between left/right limbs and
      flexor/extensor muscles. Formation of left/right alternation is presumably due to
      developmental changes in the properties of the postsynaptic neurons, themselves,
      whereas flexor/extensor alternation requires the additional emergence of
      inhibitory synaptic functions in the spinal cord.

PMID- 14653152
TI  - Reflections on respiratory rhythm generation.
AB  - Knowledge about neuronal mechanisms that control respiration is being advanced
      rapidly by studies that make use of both mature in vivo animals and in vitro
      neonates. The available data suggest that particular types of neurons within
      selected networks of the ventrolateral medulla are essential for respiratory
      rhythm generation. There are many uncertainties, however, about the
      correspondence between neurons identified by the above two approaches, because
      there are virtually no studies that have combined them. In this chapter, I
      propose a hypothesis that shows how neonatal respiratory neurons, with either
      retained or modified intrinsic cellular properties, develop into mature, well
      characterized respiratory neurons located in medullary areas called the Botzinger
      and pre-Botzinger complex. Currently, the most plausible models of respiratory
      rhythmogenesis are hybrid ones that include both intrinsic cellular and network
      properties.

PMID- 14653151
TI  - The maturation of locomotor networks.
AB  - In both vertebrates and invertebrates, the elaboration of locomotion, and its
      neural control by the central nervous system, are extremely flexible. This is due
      not only to the network properties of relevant sets of central neurons, but also
      to the active participation of mutually co-operative central and peripheral loops
      of neural projections and activity. In this chapter, we describe experiments in
      which the above concepts have been advanced by comparing locomotor properties in
      the adult vs. neonatal rat preparation. Data obtained from the in vivo vs. in
      vitro preparation, and swimming vs. walking behavior, suggest that the locomotor
      pattern progressively exhibited after birth corresponds to successive steps in
      the maturation of locomotor networks. Our work emphasises that during the late
      pre- and early postnatal period, three distinct neural entities--segmental
      sensory input, descending pathways, and motoneurons--play a key role in the
      maturation of locomotion and its neural control. We propose that the neonatal rat
      preparation is an excellent model for studying the conversion from immature to
      adult locomotion. Some neural controls are more clearly demonstrable in the
      developing animal preparation than in the adult because the latter exhibits an
      array of complex and redundant adaptive mechanisms.

PMID- 14653153
TI  - Key mechanisms for setting the input-output gain across the motoneuron pool.
AB  - This chapter summarizes a number of factors that control the "input-output"
      function across the motoneurons (MNs) comprising a single spinal motor nucleus.
      The main focus is on intrinsic properties of individual MNs that can be
      controlled by neuromodulators. These include: (1) amplification of the synaptic
      input at the cell's dendritic level by voltage-gated, persistent inward currents
      (plateau potentials); and (2) transduction of the net synaptic excitation into a
      frequency code (the MN's stimulus current-spike frequency relation) at the cell's
      soma/initial segment. Two other aspects of the synaptic control of MNs, which may
      affect their input-output gain, are also discussed. They include the hypotheses
      that: (1) a non-uniform distribution of synaptic effects to low- and high
      threshold motor units causes a change in recruitment gain; and (2) recurrent
      inhibition, via motor axon collaterals and Renshaw cells, functions as a variable
      gain regulator of MN discharge.

PMID- 14653154
TI  - Rhythm generation for food-ingestive movements.
AB  - In vitro block preparations of the central nervous system (CNS) are particularly
      valuable for study of central neuronal mechanisms controlling the respiratory and
      locomotor rhythms. No comparable in vitro preparation has been described
      previously, however, for analysis of analogous feeding rhythms. In this chapter,
      we present such a model. It is comprised of an in vitro brainstem-spinal cord
      preparation isolated from the newborn rat and mouse. Bath application to this
      preparation of N-methyl-D-aspartate (NMDA) induces rhythmical burst activity in
      the V, VII and XII nerves, which, collectively, is indicative of feeding
      behavior. Selected transections of the brainstem reveal that the central sucking
      rhythm generators for such V, VII and XII activity are separate from one another,
      and located segmentally in the brainstem at the level of their respective motor
      nuclei. We believe that use of this in vitro preparation will advance
      understanding of the central neuronal mechanisms controlling sucking and
      mastication, and the developmental transition from sucking to mastication.

PMID- 14653155
TI  - Do respiratory neurons control female receptive behavior: a suggested role for a
      medullary central pattern generator?
AB  - Nucleus retroambiguus (NRA) consists of a column of neurons in the caudal medulla
      with crossed descending axons that terminate in almost all spinal segments. Many
      of these neurons transmit the drive for expiratory movements to the spinal cord.
      The same neurons are also known to participate, however, in other motor acts,
      such as vomiting and abdominal straining, for which it appears that the medullary
      circuits controlling the respiratory pattern are reconfigured. Plasticity in
      projections from the NRA to hindlimb motor nuclei provides evidence that some of
      these projections are involved in yet another motor act, female receptive
      behavior. Here, we present the hypothesis that the medullary circuits are also
      reconfigured to act as a central pattern generator for this behavior. In
      addition, we suggest that during estrus, plasticity is shown not only in spinal
      cord connections, but also in a selected membrane property of hindlimb
      motoneurons.

PMID- 14653156
TI  - The central pattern generator for forelimb locomotion in the cat.
AB  - This chapter addresses the neuronal organization of the central pattern generator
      (CPG) for forelimb locomotion in the cat. The focus is on fictive locomotion, as
      induced by repetitive stimulation of the cervical lateral funiculus (CLF) in the
      decerebrate preparation. The stimulus time-locked responses of cervical
      motoneurons (MNs) that follow each current pulse of such repetitive stimulation
      include disynaptic EPSPs, trisynaptic EPSPs and IPSPs, and polysynaptic PSPs.
      Their amplitudes are all phase-related to selected aspects of the locomotor
      rhythm, as determined by the pattern of discharge in nerves to selected muscles.
      Correlation analysis reveals rhythmic modulation between the responses of
      extensor and flexor MNs, thereby suggesting mutual interactions between pathways
      mediating the CLF effects on MNs. It is argued that the shortest CLF pathway to
      MNs via the CPG is disynaptic: i.e., with only a single intercalated interneuron
      (IN) between the descending command axons and the MNs. A second proposal is that
      such intercalated INs contribute to interacting, reverberating IN circuits (i.e.,
      the CPG) through mutual excitation.

PMID- 14653157
TI  - Generating the walking gait: role of sensory feedback.
AB  - In the walking system of the cat, feedback from muscle proprioceptors establishes
      the timing of major phase transitions in the motor pattern, contributes to the
      production of burst activity, generates some features of the motor pattern, and
      is required for the adaptive modification of the motor pattern in response to
      alterations in leg mechanics. How proprioceptive signals are integrated into
      central neuronal networks has not been fully established, largely due to the
      absence of detailed information on the functional characteristics of central
      networks in the presence of phasic afferent signals. Nevertheless, it appears
      likely that afferent signals reorganize the functioning of central networks, and
      the concept that the generation of the motor pattern can be explained by afferent
      modulation of a hard-wired central pattern generator may be too simplistic.

PMID- 14653158
TI  - Cellular transplants: steps toward restoration of function in spinal injured
      animals.
AB  - Severe spinal cord injury results in severe, persisting deficits with little hope
      for substantial recovery. Recent developments in transplantation protocols, gene
      therapy, and methods of evaluation now offer hope of developing treatments that
      will lead to better prognoses. This review discusses the consequences of spinal
      injury, animal models used to study injury and recovery, types of cellular
      transplants, selection of behavioral and physiological tests of recovery, and
      ways to test the efficacy of the interventions and to improve transplant-mediated
      recovery.

PMID- 14653159
TI  - Neurotrophic effects on dorsal root regeneration into the spinal cord.
AB  - Dorsal root ganglion neurons exhibit a robust and generally successful
      regenerative response following injury of their peripheral processes.
      Regeneration fails, however, after section of their central processes in the
      dorsal roots or dorsal columns. Experiments characterizing the attenuated
      response of these neurons to injury, and the inhibition of regeneration exerted
      by astrocytes and oligodendrocytes within the dorsal root entry zone and spinal
      cord, have contributed important insights into the failure of regeneration after
      injury to the central nervous system (CNS). Interventions that have enhanced the
      metabolic response of injured dorsal root ganglion neurons, and altered the
      inhospitable environment, have increased sensory afferent regeneration and
      recovery. There is reason to expect that these strategies will help to develop
      clinically applicable treatments of CNS injuries.

PMID- 14653160
TI  - Effects of an embryonic repair graft on recovery from spinal cord injury.
AB  - It is widely believed that mammalian CNS axons have little regenerative capacity
      because their environment is non-permissive to regrowth. This viewpoint is based,
      in large part, on the fact that in virtually all previous studies on regeneration
      following spinal cord injury, regenerated axonal projections have been few in
      number, quite short, and considered to be mostly aberrant. As a result, motor
      recovery has been very limited in both experimental preparations and the human.
      In this chapter, we describe use of a neonatal, spinally transected animal model
      in which selected spinal cord segments were carefully replaced with equivalent
      tissue from embryonic tissue of the same species. We demonstrate that the new
      spinal environment is indeed permissive, and reconstruction is possible of neural
      connections, which are similar to the pre-injury, normal projections. Moreover,
      the distribution and number of regenerated axons are closely related to the
      extent of functional motor recovery. Our results suggest that contrary to
      doctrinaire thought, the mammalian CNS possesses a remarkable capacity for
      regrowth. For this to be efficacious, however, regenerating axons must contact
      the inherent, pre-injury guidance system, whose cues were used for establishing
      appropriate neural connections in the developing animal, and are retained in the
      adult. It is argued that by use of these guidance cues, regenerating axons that
      traverse the site of a spinal cord injury, can project on to locate their pre
      injury pathways and targets, and thereby restore function.

PMID- 14653161
TI  - Determinants of locomotor recovery after spinal injury in the cat.
AB  - After a spinalization at the most caudal thoracic spinal segment, the cat can
      recover locomotion of the hindlimbs when they are placed on a moving treadmill.
      This chapter summarizes some of the determinants of such a dramatic recovery of
      motor function. Fundamental to this recovery is undoubtedly the genetically based
      spinal locomotor generator, which provides an essential rhythmicity to spinal
      motoneurons and hence the musculature. Other factors are also important, however.
      Sensory feedback is essential for the correct expression of spinal locomotion
      because spinal cats, devoid of cutaneous feedback from the hindfeet, are
      incapable of plantar foot placement. The neurochemical environment also adapts to
      spinalization, i.e., the loss of all modulation by descending monoaminergic
      pathways. Post-transection spinal rhythmicity then becomes more dependent on
      glutamatergic mechanisms. Finally, we argue that the mid-lumbar spinal segments
      evolve to play a crucial role in the elaboration of spinal locomotion as their
      inactivation abolishes spinal locomotion. In summary, the above findings suggest
      that the recovery of spinal locomotion is determined by a number of factors, each
      of which must now be more fully understood in the ever-continuing effort to
      improve the rehabilitation of spinal-cord-injured subjects.

PMID- 14653162
TI  - Trunk movements and EMG activity in the cat: level versus upslope walking.
AB  - This chapter addresses the neural control of spinal-column behavior during
      locomotion. Kinematic and EMG measurements were obtained from the adult cat
      during its level and upslope treadmill walking. Increasing the grade of upslope
      walking augmented horizontal movements of the spinal column and decreased its
      lateral movements. In conjunction, there were significant increases in the
      amplitude, duration, and pattern of EMG bursts in relevant spinal column
      musculature. During even steeper upslope walking, three EMG bursts were evident.
      They were phase-locked to the outward, downward and backward movements of the
      spinal column, respectively. Our results suggest that the component of the
      locomotor pattern generator that produces rhythmical spinal column movements must
      generate a wide variety of EMG bursts in spinal column muscles, as dependent in
      part on sensory input from the spinal column and its musculature.

PMID- 14653163
TI  - Biomechanical constraints in hindlimb joints during the quadrupedal versus
      bipedal locomotion of M. fuscata.
AB  - The operant-trained Japanese monkey, Macaca fuscata, can walk with both a
      quadrupedal (Qp) and a bipedal (Bp) gait on the surface of a treadmill belt,
      which moves at different speeds. The animal can also learn to transform its
      locomotor pattern from Qp to Bp, and vice versa, without a break in forward
      walking speed. This nonhuman primate model provides an intriguing opportunity to
      compare the kinematics of multiple body segments during Qp and Bp walking of the
      same subject. We found that M. fuscata selects a postural strategy and limb
      kinematic parameters appropriate for the execution of both gaits. We propose that
      the basic locomotor rhythm-generating mechanisms of the brainstem and spinal
      cord, which are genetically endowed and relatively automatized, are used for the
      execution of both the Qp and Bp gait. The latter requires in addition, however,
      some higher-level circuitry which is shaped substantially by motor learning
      mechanisms.

PMID- 14653164
TI  - Reactive and anticipatory control of posture and bipedal locomotion in a nonhuman
      primate.
AB  - Bipedal locomotion is a common daily activity. Despite its apparent simplicity,
      it is a complex set of movements that requires the integrated neural control of
      multiple body segments. We have recently shown that the juvenile Japanese monkey,
      M. fuscata, can be operant-trained to walk bipedally on moving treadmill. It can
      control the body axis and lower limb movements when confronted by a change in
      treadmill speed. M. fuscata can also walk bipedally on a slanted treadmill.
      Furthermore, it can learn to clear an obstacle attached to the treadmill's belt.
      When failing to clear the obstacle, the monkey stumbles but quickly corrects its
      posture and the associated movements of multiple motor segments to again resume
      smooth bipedal walking. These results give indication that in learning to walk
      bipedally, M. fuscata transforms relevant visual, vestibular, proprioceptive, and
      exteroceptive sensory inputs into commands that engage both anticipatory and
      reactive motor mechanisms. Both mechanisms are essential for meeting external
      demands imposed upon posture and locomotion.

PMID- 14653165
TI  - Neural control mechanisms for normal versus parkinsonian gait.
AB  - The non-invasive methods which can be applied to the study of the cerebral
      control mechanisms for human gait are limited because of technical constraints.
      In particular, the subject's head has to be fixed for most measurements. Despite
      this problem, SPECT-detected, rCBF activation studies have shown that the
      cerebral cortex participates in the control of the normal volitional walking of
      healthy human subjects. The active brain areas include the foot and trunk regions
      of the primary sensorimotor cortex, and the supplementary motor area (SMA),
      lateral premotor cortex, and cingulated gyrus. Selected subcortical structures
      also exhibit walking-related activity, including the dorsal brainstem and
      cerebellum. These same regions are active in patients with Parkinson's disease
      (PD), but significantly less so in the right SMA, left precuneus, and right
      cerebellar hemisphere. For the "kinesie paradoxale" of PD patients, the right
      lateral premotor area plays an important role in the visually induced gait
      improvement brought on by adding transverse lines to the walking path.

PMID- 14653166
TI  - Multijoint movement control: the importance of interactive torques.
AB  - The underlying mechanisms of the neural control of movement have long been
      explored, with a focus primarily on central control aspects and often overlooking
      the intrinsic mechanical properties of the motor system. To fully understand the
      control and regulation of movements, the biomechanical properties of the moving
      subject, specifically interactive torques, must be considered in the design,
      evaluation, and interpretation of empirical data. We first discuss the difficulty
      of extrapolating information from a wide variety of tasks due to their varying
      inherent task constraints. Examples are subsequently given where a biomechanical
      perspective provides a more informative interpretation of existing data. Finally,
      we focus on research examining the role of interactive torques with a discussion
      of how discoordinated movements may be explained by an inability to modulate
      interactive torques. Inclusion of biomechanical considerations in motor control
      research is a step toward incorporating multilevel methodologies and
      interpretations into the field, and providing a more comprehensive understanding
      of the neural control and regulation of movement.

PMID- 14653167
TI  - How the mesencephalic locomotor region recruits hindbrain neurons.
AB  - This chapter summarizes experiments which were designed to reveal how repetitive
      electrical stimulation of the mesencephalic locomotor region (MLR) recruits
      nearby hindbrain neurons into activity, such that locomotion can ensue in the
      tiger salamander, A. tigrinum. The MLR stimulus strength was subthreshold or near
      threshold for locomotor movements to ensue. Such relatively weak stimulation of
      the MLR produced locomotor movements after a relatively long delay, which
      featured neuronal interactions in the hindbrain. MLR-evoked spike responses of
      single hindbrain neurons were recorded before locomotor movements began. This
      allowed consideration of the build-up of the hindbrain neuronal activity, which
      was subsequently impressed upon the spinal cord such as to evoke locomotor
      movements. Each train of MLR stimulus pulses evoked monosynaptic responses in but
      a small proportion of the hindbrain's neurons. Rather, oligosynaptic responses
      were routinely evoked, even in the "input" neurons that were activated
      monosynaptically. Consecutive stimulus volleys recruited a given neuron after a
      variable number of synaptic translations. It is argued that the hindbrain's input
      neurons excited a much larger number of other hindbrain neurons. By this means,
      an MLR-evoked, short-lived propagating wave of excitation (i.e., approximately 2
      4 successive synaptic activations) can be spread throughout the hindbrain.

PMID- 14653168
TI  - Role of basal ganglia-brainstem systems in the control of postural muscle tone
      and locomotion.
AB  - This chapter argues that a basal ganglia-brainstem system throughout the
      mesopontine tegmentum contributes to an automatic control of movement that
      operates in conjunction with voluntary control processes. Activity of a muscle
      tone inhibitory system and the locomotion executing system can be steadily
      balanced by a net excitatory cortical input and a net inhibitory basal ganglia
      input to these systems. We further propose that dysfunction of the basal ganglia
      brainstem system, together with that of the cortico-basal ganglia loop, underlies
      the pathogenesis of motor disturbances expressed in basal ganglia diseases.

PMID- 14653169
TI  - Locomotor role of the corticoreticular-reticulospinal-spinal interneuronal
      system.
AB  - In vertebrates, the descending reticulospinal pathway is the primary means of
      conveying locomotor command signals from higher motor centers to spinal
      interneuronal circuits, the latter including the central pattern generators for
      locomotion. The pathway is morphologically heterogeneous, being composed of
      various types of inparallel-descending axons, which terminate with different
      arborization patterns in the spinal cord. Such morphology suggests that this
      pathway and its target spinal interneurons comprise varying types of functional
      subunits, which have a wide variety of functional roles, as dictated by command
      signals from the higher motor centers. Corticoreticular fibers are one of the
      major output pathways from the motor cortex to the brainstem. They project widely
      and diffusely within the pontomedullary reticular formation. Such a diffuse
      projection pattern seems well suited to combining and integrating the function of
      the various types of reticulospinal neurons, which are widely scattered
      throughout the pontomedullary reticular formation. The corticoreticular
      reticulospinal-spinal interneuronal connections appear to operate as a cohesive,
      yet flexible, control system for the elaboration of a wide variety of movements,
      including those that combine goal-directed locomotion with other motor actions.

PMID- 14653170
TI  - Cortical and brainstem control of locomotion.
AB  - While a basic locomotor rhythm is centrally generated by spinal circuits,
      descending pathways are critical for ensuring appropriate anticipatory
      modifications of gait to accommodate uneven terrain. Neurons in the motor cortex
      command the changes in muscle activity required to modify limb trajectory when
      stepping over obstacles. Simultaneously, neurons in the brainstem reticular
      formation ensure that these modifications are superimposed on an appropriate base
      of postural support. Recent experiments suggest that the same neurons in the same
      structures also provide similar information during reaching movements. It is
      suggested that, during both locomotion and reaching movements, the final
      expression of descending signals is influenced by the state and excitability of
      the spinal circuits upon which they impinge.

PMID- 14653171
TI  - Direct and indirect pathways for corticospinal control of upper limb motoneurons
      in the primate.
AB  - In the macaque monkey and in humans, the monosynaptic cortico-motoneuronal system
      is well developed. It allows the cortical motor areas to make an important direct
      contribution to the pattern of muscle activity during upper limb movements. There
      is, in addition, good anatomical evidence for descending corticospinal inputs
      being able to influence the premotoneuronal networks of the cervical spinal cord,
      and especially those operating at the segmental level of upper limb motoneurons.
      While oligosynaptic inhibition has been easy to demonstrate in the macaque, and
      may be a very important component of descending corticospinal control, it has
      proved much more difficult to detect signs of oligosynaptic excitation. In
      contrast, in the squirrel monkey, in which the cortico-motoneuronal system is far
      less developed, oligosynaptic excitation is prominent. There are important
      changes in the interplay between direct and indirect pathways in different
      primates, which may provide important clues on the nature of the corticospinal
      control of upper limb function.

PMID- 14653172
TI  - Arousal mechanisms related to posture and locomotion: 1. Descending modulation.
AB  - Much of the controversy surrounding the induction of locomotion following
      stimulation of mesopontine sites, including the pedunculopontine nucleus (PPN),
      appears based on procedural differences, including stimulus onset, delay
      preceding stepping, and frequency of stimuli. The results reviewed in this
      chapter address these issues and provide novel information suggesting that
      descending projections from the PPN may exert a frequency-dependent effect.
      Stimulation at approximately 60 Hz (which induces prolonged tonic firing) may
      exercise a "push" towards locomotion (activation of pontine interneurons) as well
      as a "pull" away from decreased muscle tone (inhibiting giant pontine
      reticulospinal cells). Higher frequencies of stimulation (> 100 Hz, which induces
      phasic burst-like activity) may "push" towards decreases in muscle tone,
      including the atonia of rapid eye movement sleep (activating giant pontine
      reticulospinal cells).

PMID- 14653173
TI  - Arousal mechanisms related to posture and locomotion: 2. Ascending modulation.
AB  - An intrinsic function of the reticular activating system (RAS) is its
      participation in fight vs. flight responses such that alerting stimuli
      simultaneously activate thalamocortical systems, as well as postural and
      locomotor systems, in order to enable an appropriate response. The P50 midlatency
      auditory-evoked potential appears to be an ascending manifestation of the
      cholinergic arm of the RAS in eliciting changes in arousal state. Abnormalities
      in the manifestation of the P50 potential are present in disorders which include:
      (1) dysregulation of sleep-wake cycles; (2) abnormalities in reflex/postural,
      especially, startle, responses; and (3) malfunctions in flight vs. flight
      responses. In general, the P50 potential appears to be upregulated (increased
      amplitude and/or decreased sensory gating) in disorders which are marked by
      upregulation of RAS outputs (hypervigilance), and downregulated in disorders
      characterized by decreased RAS outputs (hypovigilance). Many of the disorders
      discussed have a developmental etiology and a postpubertal age of onset.

PMID- 14653174
TI  - Switching between cortical and subcortical sensorimotor pathways.
AB  - It is well known that the reaction times of visually guided saccades exhibit a
      bimodal distribution. Those with extremely short reaction times are termed
      'express saccades'. In their case, visual input appears to be transformed into
      motor output via a 'short-loop', brainstem-mediated pathway. In contrast, those
      with longer reaction times are called 'regular saccades'. The latter are
      presumably executed via a cortically mediated, 'long-loop' sensorimotor pathway.
      The 'gate' that switches signal flow between the short and long loop is thought
      to be located in between the superficial and deeper layers of the superior
      colliculus (SC). Nonlinear signal amplification mechanisms, which operate in
      local circuits of the deeper SC layers may underlie this gating function, with
      switching of the gate regulated in a context-dependent manner by inputs from the
      cerebral cortex and basal ganglia.

PMID- 14653175
TI  - Cerebellar activation of cortical motor regions: comparisons across mammals.
AB  - This chapter discusses the nature of mammalian cerebello-thalamo-cortical
      projections. These play an important role in motor control, but with species
      differences evident in the innervation patterns of thalamo-cortical (T-C) fibers
      relaying cerebellar inputs. A phylogenetic comparison of the mode of cerebellar
      activation of cortical motor regions reveals that cerebellar inputs are relayed
      by the deep and superficial T-C projections in the cat, but predominately by the
      latter in rat and monkey. Another difference across mammals is the nature of
      cerebellar activation of cortical neurons. Fast-conducting pyramidal tract
      neurons in the cat routinely receive fast-rising EPSPs from the deep cerebellar
      nuclei (CN). This tendency is not observed in rat and monkey, however. These
      findings suggest that the responsiveness of cortical output neurons also shows
      species differences, these having bearing on the development of species-specific
      motor skills. Common to all three species, however, are fast-rising and large CN
      EPSP responses of layer III pyramidal neurons to CN input. It is argued that
      layer III pyramidal neurons modulate cerebellar input to layer V pyramidal
      neurons, which latter cells provide command signals from the motor cortex to the
      lower centers.

PMID- 14653176
TI  - Task-dependent role of the cerebellum in motor learning.
AB  - This chapter reviews several findings from our laboratory supporting the
      hypothesis that the cerebellum's role in motor learning is task-dependent.
      Namely, its contribution is dependent on the specific task being learned. Several
      studies are reviewed to demonstrate that the effect of temporary or permanent
      cerebellar lesions on a specific process such as storage varies depending on the
      behavior. Furthermore, this task-dependency is reflected also in the modulation
      of Purkinje cells and nuclear neurons recorded during the learning process. The
      behavioral correlates of this modulation are very paradigm specific. These
      observations support the above hypothesis and emphasize the importance of
      paradigm selection in designing experiments focused on elucidating the
      cerebellum's role in learning a specific motor behavior.

PMID- 14653177
TI  - Role of the cerebellum in eyeblink conditioning.
AB  - The mammalian cerebellum is thought to participate in motor control and motor
      learning. The specific cerebellar contribution to these processes is not clear,
      however. Advances in understanding cerebellar function have been relatively slow,
      because, at least in most cases, the cerebellum appears to play only an ancillary
      role in the behaviors studied to date. A remarkable exception is classical
      conditioning of eyeblink responses in the rabbit. In this model, an intact
      cerebellum is critical for both the acquisition and expression of conditioned
      responses. Recent experiments suggest that the cerebellar role in classical
      conditioning might be similar in all mammals, including the human. Moreover,
      anticipatory defensive reflexes in other effector systems show a similar
      dependence on the intermediate cerebellum. Further developments in our
      understanding of cerebellar function will depend on examination of a wider array
      of cerebellar-involved neural networks. There is also need for the development of
      new experimental approaches to associative learning in both the nonhuman primate
      and the human.

PMID- 14653178
TI  - Integration of multiple motor segments for the elaboration of locomotion: role of
      the fastigial nucleus of the cerebellum.
AB  - This chapter provides a conceptual overview of the role and operation of higher
      structures of the central nervous system (CNS) in the control of posture and
      locomotion in the mammal, including the nonhuman primate and the human. Both
      quadrupedal and bipedal locomotion require the integrated neural control of
      multiple body segments against gravity. During development, and in selected
      instances in the adult, motor learning is required, particularly for merging
      anticipatory and reactive CNS processes, the latter being necessary after
      tripping and stumbling. We have recently found that the fastigial nucleus (FN) of
      the cerebellum in the cat plays a particularly important role in the control of
      locomotion, by virtue of its critical position in uniting the cerebro-cerebellar
      and the spino-cerebellar loops of neural activity that participate in the
      integrated control of multiple body segments. Further understanding of the CNS
      structures that achieve this integration has come from our recent study of an
      intact nonhuman primate, the Japanese monkey, Macaca fuscata, as it learns to
      elaborate bipedal locomotion rather than its normal quadrupedal fashion. Based on
      findings from these two animal species, we now present a model of the overall
      integrated control of posture and locomotion that features the combined operation
      of parallel and distributed neural circuitry throughout the CNS.

PMID- 14653179
TI  - Role of the cerebellum in the control and adaptation of gait in health and
      disease.
AB  - In humans, inability to stand and walk is the most limiting of motor
      disabilities. In humans, upright stance and gait is the most sensitive indicator
      of cerebellar disease. From animal and human studies, much has been learned about
      how the cerebellum coordinates normal movement, and how it may play roles in
      normal motor adaptation and learning. Much of this work suggests that different
      parts of the cerebellum control stance and gait in different ways, and
      differently located lesions cause different deficits. What is not known is
      whether the cerebellum can compensate for stance and gait disorders caused by
      lesions in other parts of the nervous system, or whether one part of the
      cerebellum can compensate for deficits caused by lesion of another part. These
      issues have become increasingly important in rehabilitation research and
      practice.

PMID- 14653180
TI  - Current approaches and future directions to understanding control of head
      movement.
AB  - This chapter reviews four key issues that must be addressed to advance our
      knowledge of control of head movement by the central nervous system (CNS). (1)
      Researchers must consider how the CNS utilizes the multiple muscle patterns that
      can produce the same head movement in carrying out tasks in an optimal way. (2)
      More attention must be paid to the dynamics of neck muscle activation that are
      required to implement head movements and show they are produced by CNS circuits.
      (3) Research is required to determine how the multiple pathways that impinge upon
      neck motor centers are utilized in a variety of tasks including eye-head gaze
      shifts, smooth head tracking, head stabilization and manipulating objects with
      the head. These pathways include corticospinal, vestibulospinal, reticulospinal
      (three subdivisions), fastigiospinal, tectospinal and interstitiospinal tracts.
      (4) Further analysis is needed to understand how vestibular signals are modulated
      during each of the above-mentioned tasks. This ambitious agenda is justified by
      the fact that the head-neck motor system is an ideal model for understanding
      issues of complex motor control.

PMID- 14653181
TI  - The neural control of orienting: role of multiple-branching reticulospinal
      neurons.
AB  - This chapter emphasizes the functional significance of the multiple-branching
      patterns of descending axons implicated in the control of movement. The example
      provided concerns orienting head movements, which are controlled by pathways from
      the superior colliculus (SC). Such control is mediated via cervical
      reticulospinal neurons (C-RSNs), which take origin in the nucleus reticularis
      pontis caudalis and nucleus reticularis gigantocellularis, and give off multiple
      collaterals along the full length of their axonal trajectory. Their projection is
      not only to lamina IX neck motor nuclei in upper cervical segments, but also to
      laminae VII-VIII in lower cervical segments. Thus, SC commands for head orienting
      are transmitted to both neck motoneurons and lower cervical spinal circuitry,
      which latter network controls appropriate postural adjustments by the coordinated
      control of motoneurons supplying the four limbs.

PMID- 14653182
TI  - Role of the frontal eye fields in smooth-gaze tracking.
AB  - Visual and vestibular senses are essential for appropriate motor behavior in
      three-dimensional (3D) space. Discovery of relevant specific subdivisions in
      sensory and motor pathways in recent decades has considerably advanced our
      understanding of the overall neural control of movement. Such subdivisions must
      eventually be further delineated into functional neural circuits for purposeful
      motor acts. Two critical questions are where in the brain do such circuits
      operate, and by what means. In this chapter, these issues are addressed for
      smooth tracking eye-movement systems in the simian. These results show that
      contrary to current understanding, synthesis of the functionally similar eye
      movement systems, smooth-pursuit and vergence, takes place in the frontal cortex.
      This processing, which is of higher order than previously supposed, enables
      primates to track and manipulate objects moving in 3D space with the utmost of
      efficiency.

PMID- 14653183
TI  - Role of cross-striolar and commissural inhibition in the vestibulocollic reflex.
AB  - In the otolith system, there are two types of neuronal circuitry that can enhance
      response sensitivity during linear acceleration and tilt of the head. One
      produces cross-striolar inhibition and the other commissural inhibition. Cross
      striolar inhibition can be observed in over 50% of saccular-activated, second
      order vestibular neurons. In contrast, it is seen in less than 33% of utricular
      activated, second-order vestibular neurons. The majority of vestibular neurons
      that receive cross-striolar inhibition have axons that project to the spinal
      cord. Over 50% of the utricular-activated, second-order vestibular neurons
      received commissural inhibition from the contralateral utricular nerve. On the
      other hand, almost all the saccular-activated, second-order vestibular neurons
      exhibit no response to stimulation of the contralateral saccular nerve. The
      majority of vestibular neurons receiving commissural inhibition also have axons
      that project to the spinal cord. These results suggest that cross-striolar
      inhibition is important for increasing the sensitivity of the saccular system,
      whereas commissural inhibition is more important in the utricular system.

PMID- 14653184
TI  - Functional synergies among neck muscles revealed by branching patterns of single
      long descending motor-tract axons.
AB  - In this chapter, we describe our recent work on the divergent properties of
      single, long descending motor-tract neurons in the spinal cord, using the method
      of intra-axonal staining with horseradish peroxidase, and serial-section, three
      dimensional reconstruction of their axonal trajectories. This work provides
      evidence that single motor-tract neurons are implicated in the neural
      implementation of functional synergies for head movements. Our results further
      show that single medial vestibulospinal tract (MVST) neurons innervate a
      functional set of multiple neck muscles, and thereby implement a canal-dependent,
      head-movement synergy. Additionally, both single MVST and reticulospinal axons
      may have similar innervation patterns for neck muscles, and thereby control the
      same functional sets of neck muscles. In order to stabilize redundant control
      systems in which many muscles generate force across several joints, the CNS
      routinely uses a combination of a control hierarchy and sensory feedback. In
      addition, in the head-movement system, the elaboration of functional synergies
      among neck muscles is another strategy, because it helps to decrease the degrees
      of freedom in this particularly complicated control system.

PMID- 14653185
TI  - Control of orienting movements: role of multiple tectal projections to the lower
      brainstem.
AB  - In movement neuroscience this past decade, a conceptual approach that puts
      emphasis on population coding was clearly dominant. The purpose of numerous
      studies has been to define presumably homogeneous groups of neurons on the basis
      of the correlation of their discharges with sensory and motor events. The goal of
      this chapter is to stress the importance of taking into account individual
      properties of neurons, this being an essential prerequisite for a biologically
      meaningful definition of neuron populations. Taking as an example the executive
      limb of the neural network controlling gaze movements, we demonstrate the
      functional and anatomical diversity of tectal and reticular neurons, which are
      generally considered as homogeneous populations and used, accordingly, as lumped
      elements in models. We argue that the extraction of effector-specific signals
      from the global command of gaze displacement is based not on the interplay
      between discrete neural modules, but rather on a gradual process of signal
      specification at all levels of the executive network. An eventual accurate
      description of this network will require knowledge of the unique combinations of
      afferent inputs and efferent connections for as many subsets of its constituent
      neurons as is conceivably possible.

PMID- 14653186
TI  - Pedunculo-pontine control of visually guided saccades.
AB  - The cholinergic pedunculopontine tegmental nucleus (PPTN) is one of the major
      ascending arousal systems in the brainstem, and it is linked to motor, limbic and
      sensory centers. Despite an abundance of anatomical and physiological data,
      however, the functional role of PPTN neurons in behavioral control is still
      unresolved. In this chapter, we hypothesize that the PPTN is implicated in the
      integrative control of movement, particularly the reinforcement of tasks
      performed during conscious behavior. We present a new model of the PPTN's
      involvement in the control of arousal, attention and reinforcement aspects of
      motor behavior, with a focus on the control of saccadic eye movements.

PMID- 14653188
TI  - A new dynamic model of the cortico-basal ganglia loop.
AB  - An important issue in the neural control of posture and movement is how motor
      related areas of the cerebral cortex modulate the activity of the output nuclei
      of the basal ganglia. In this chapter, the functional significance of the
      'hyperdirect' cortico-subthalamo-pallidal pathway is emphasized, and further a
      new dynamic model of basal ganglia function is presented. When a voluntary
      movement is about to be initiated by cortical mechanisms, a corollary signal is
      conveyed through the 'hyperdirect' pathway to first inhibit large areas of the
      thalamus and cerebral cortex that are related to both the selected motor program
      and other competing programs. Next, another corollary signal is sent through the
      'direct' cortico-striato-pallidal pathway to disinhibit this second pathway's
      targets, and ensure activation of only the selected motor program. Finally, a
      third corollary signal is sent through the 'indirect' cortico-striato-external
      pallido-subthalamo-internal pallidal pathway to strongly inhibit this third
      pathway's targets. This sequential information processing ensures that only the
      selected motor program is initiated, executed and terminated at the appropriate
      times, whereas other competing programs are canceled.

PMID- 14653187
TI  - Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies
      virus to reveal multisynaptic circuits.
AB  - We have used retrograde transneuronal transport of rabies virus to examine basal
      ganglia connections with the cerebral cortex. We injected rabies into the primary
      motor cortex (M1) or into Area 46 of cebus monkeys. A 4-day survival time was
      long enough to allow transport of rabies from the injection site to 'third-order'
      neurons in the basal ganglia. After either M1 or Area 46 injections, third-order
      neurons were found in the external segment of the globus pallidus (GPe), striatum
      and subthalamic nucleus (STN). In each of these nuclei, the third-order neurons
      that innervate M1 were spatially separated from those that innervate Area 46.
      Thus, distinct basal ganglia-thalamocortical circuits innervate M1 and Area 46.
      Next, we injected a conventional tracer into M1 to define its terminations in the
      putamen and STN. We found that the regions of the putamen and STN that receive
      input from M1 are the same as those that contain third-order neurons after M1
      injections of virus. On the other hand, virus injections into M1 also labeled a
      relatively dense group of third-order neurons in a region of the ventral putamen
      that is not innervated by M1. This region of the putamen is the target of
      efferents from the amygdala. Thus, the ventral putamen may provide a route for
      the limbic system to influence motor output. Overall, our results indicate that
      basal ganglia circuits with the cerebral cortex can be characterized by both open
      and closed-loop macro-architectures.

PMID- 14653189
TI  - Functional recovery after lesions of the primary motor cortex.
AB  - After a lesion in the motor cortex of an adult primate, are cortical motor maps
      reorganized? This important question has attracted much interest throughout the
      past decade. In human subjects, substantial progress has resulted from the use of
      noninvasive imaging and stimulation techniques. For example, there is recent,
      well-accepted, albeit indirect evidence that following such a lesion on one side
      of the human brain, a dramatic reorganization of the hand representation occurs
      within either the ipsilateral primary motor cortex, nonprimary motor areas or
      both. The contribution of contralateral motor areas to functional recovery of the
      paretic hand remains uncertain, however, because of the lack of direct
      confirmatory evidence obtained from experiments undertaken on nonhuman primates.
      A better understanding of how the brain selects the optimal strategy for
      functional recovery following cortical lesions, and the neuronal mechanisms
      underlying cortical plasticity, will be important challenges for the next decade.
      To this end, the purpose of the present chapter is to provide an update on what
      is truly known about the functional recovery that takes place after a lesion in
      the primary motor cortex of both the nonhuman primate and the human. It bears
      emphasis that work on these fundamental issues is an essential prerequisite to
      the development of improved therapeutic and rehabilitation procedures for the
      brain-injured human.

PMID- 14653190
TI  - Adaptive behavior of cortical neurons during a perturbed arm-reaching movement in
      a nonhuman primate.
AB  - This chapter provides evidence of spatial and temporal changes in the behavior of
      neurons within Areas 5 and 4 of the sensorimotor cortex of a nonhuman primate
      while it was executing a perturbed arm-reaching task. Chronically implanted
      electrode arrays were used to record simultaneously from 37 to 58 neurons. Also
      measured were the trajectory of arm movement, EMG activity in selected arm
      muscles and the perturbation force applied to the arm. The adaptation in Area 4
      neurons' behavior usually involved a reduction in the latency from the onset of
      the perturbation to the peak-firing rate of the cell. In contrast, Area 5 neurons
      exhibited no such adaptive change in this latency. In each cortical area, the
      adaptation was not uniform across all neurons, and the spatial pattern of
      neuronal population behavior changed over the period of behavioral adaptation. We
      also found that the direction of arm movement and its configuration were
      important in determining which control strategy (predictive trajectory
      compensation or stiffness control) the animal used to overcome the externally
      applied perturbation for an improved performance of the reaching task.

PMID- 14653191
TI  - The quest to understand bimanual coordination.
AB  - Many skillful manipulations engage both hands for goal achievement. Whereas the
      goal is planned consciously and achieved quasi-invariantly, the articulators are
      mobilized automatically, but in a flexible manner (Lashley's principle of motor
      equivalence). In brain disorders affecting hand functions, adaptive mechanisms
      are mobilized to improve goal achievement. Thus, chronic cerebellar patients were
      found to initiate a bimanual drawer task with marked intermanual
      desynchronization as compared to control subjects. This was partly compensated
      for, however, by adjusting the kinematics as the individual limbs move toward the
      goal, thereby improving the initial desynchronization. Adaptive strategies rarely
      correct deficits completely, however. Bimanual movement patterns, either in-phase
      or anti-phase are relatively stable in healthy human subjects, whereas brain
      pathology may preferentially impair the anti-phase pattern. This is the case in
      patients with acquired pathology of the corpus callosum, thereby suggesting that
      this structure is important for maintaining temporally independent limb and hand
      movements.

PMID- 14653192
TI  - Functional specialization in dorsal and ventral premotor areas.
AB  - The premotor cortex (PM) in the bilateral lateral hemisphere of nonhuman primates
      and the human has been implicated in the sensorial guidance of movements. This is
      in contrast to more medial motor areas that are involved more in the temporal
      structuring of movements based on memorized information. The PM is further
      subdivided into dorsal (PMd) and ventral (PMv) parts. In this chapter, we
      describe our attempts to find differences in the use of these two areas in a
      nonhuman primate for programming future motor actions based on visual signals. We
      show that neurons in the PMv are involved primarily in receiving visuospatial
      signals and in specifying the spatial location of the target to be reached. In
      contrast, neurons in the PMd are involved more in integrating information about
      which arm to use and the target to be reached. Thus, PMd neurons are more
      implicated than those of the PMv in the preparation for a future motor action.

PMID- 14653193
TI  - Spatially directed movement and neuronal activity in freely moving monkey.
AB  - The abilities to plan a series of movements and to navigate within the
      environment require the functions of the frontal and ventromedial temporal lobes,
      respectively. Neuropsychological studies posit the existence of egocentric
      (prefrontal) and allocentric (ventromedial temporal) spatial frames of reference
      that mediate these functions. To examine neural mechanisms underlying egocentric
      and allocentric guidance of movement, we have developed behavioral and
      neurophysiological techniques for freely moving monkey. In this chapter, we
      provide evidence that the dorsolateral prefrontal cortex is important for
      egocentric spatial tasks in both the visual and tactile modalities, but it does
      not contribute to performance of an allocentric spatial task. Moreover,
      neurophysiological recordings indicate that prefrontal neurons are involved in
      monitoring the spatial nature of behavioral sequences in an egocentric memory
      task. In contrast, hippocampal neurons are active during spatially directed
      locomotion, apparently reflecting the monkey's location in a testing room. This
      discharge is independent of the task's contingencies.

PMID- 14653194
TI  - [Development of GC/MS library for analyzing pesticides and drugs].
AB  - To analyze the root components of compounds causing drug addiction, we have
      developed our own GC/MS libraries(PESTICID.LIB consisting of 20 pesticides and
      Herbicides, and DRUG.LIB with 57 drugs). We have usually utilized standardized
      agents, but gastric contents, gastric specimens, serum and urine samples from
      patients were also used for the analyses. We were able to add libraries of
      various difficult to purchase psychotropic drugs and legally restricted agents by
      extracting them from the patient samples. Comments about the retention time, the
      base peak of the mass spectrum and 5 typical ion chromatograms in the libraries
      have been useful for laboratory analysis, and consequently have improved the
      accuracy of detection and identification. They were also found to be a useful
      guideline for discrimination of the unchanged materials and the metabolites. We
      are attempting to improve the accuracy of the library to avoid the effects of GC
      column conditions such as the column size, column temperature and different
      inserts by using a retention time index.

PMID- 14653195
TI  - [Free/total prostate specific antigen ratio (%PSA) to predict probability of
      prostate cancer].
AB  - It has been reported recently that %PSA, the ratio of free-PSA(F-PSA) and total
      PSA(T-PSA), remains significantly lower in sera of patients with prostatic
      cancer(PCA) than there in cases with benign prostate hypertrophy(BPH). We
      examined %PSA can be used for differential diagnosis of PCA from BPH. Forty-seven
      non-treated Japanese patients with prostate problem were examined for PSA assays
      and biopsy. On biopsy, 25 cases were diagnosed as PCA, and 22 cases as BPH. On T
      PSA value, there were 18 cases of PCA and 8 cases of BPH whose T-PSA values were
      over 10 ng/ml. When %PSA was studied, cases with less than 15% of %PSA were found
      to be PCA exclusively(16/16), while cases with less than 20 of %PSA included 19
      PCAs and 4 BPHs. In 17 PCA patients with stage B to stage D, the %PSA was less
      than 20 except one case. T-PSA was examined in 88 cases at the checkup in our old
      age home. Four samples of which T-PAS levels were in gray zone, were assayed for
      %PSA. Two of them, with %PSA values less than 20 ng/ml, were found to be PCA,
      while the remaining two, with %PSA over 20 ng/ml, were BPH.

PMID- 14653196
TI  - [Simultaneous presence of macroamylase and macrolipase in a patient with celiac
      disease].
AB  - Celiac disease is a permanent intolerance to ingested gluten that results in
      immunologically mediated inflammatory damage of the small intestinal mucosa. Here
      we report the case of a patient with Celiac disease demonstrating simultaneous
      macroamylasemia and macrolipasemia. The patient showed persistently elevated
      levels of serum amylase and lipase. Amylase and lipase in normal serum were
      eluted from a Superdex-200 column after the 4S protein. These enzymes in the
      serum from this patient were eluted in the 19S protein. This finding indicated
      that these enzymes from this patient had a molecular weight greater than that of
      normal amylase and lipase. Immunoprecipitation assay showed that amylase was
      bound to polyclonal IgG and IgA, whereas lipase was bound to polyclonal IgA. To
      our knowledge, the simultaneous presence of macroamylase and macrolipase in the
      same patient has been previously reported in only four cases. Interestingly, two
      of those patients had Celiac disease. If macroamylase and macrolipase are
      present, the possibility of Celiac disease should be considered.

PMID- 14653197
TI  - [Education in laboratory medicine for undergraduates--laboratory medicine in core
      curriculum].
AB  - A model core curriculum for medical education was proposed in March 2001. This
      guideline is meant to serve as the essential basis of material to be mastered at
      present and as a reference for curricula to be constructed by individual medical
      schools. Laboratory medicine plays an important role in this guideline, not only
      as an essential component of diagnosis and laboratory testing in various diseases
      but also in consultation. In the Department of Clinical Pathology, Showa
      University School of Medicine, we revised the curriculum of lectures and clinical
      training in laboratory medicine according to the guideline. This revision is
      expected to improve education and result in better doctors. We also will modify
      the method for education from lectures to a tutorial system, in which laboratory
      medicine should play an important role in devising tasks for tutorials.

PMID- 14653198
TI  - [The ideal curriculum for undergraduate clinical practice training in clinical
      laboratory medical education].
AB  - A model core curriculum for medical education is proposed to serve as an
      essential basis of material to be mastered. The fundamental laboratory techniques
      specified by this curriculum are the following five items. 1. Ability to
      appropriately record a 12-lead EKG. 2. Ability to perform urinalysis. 3. Ability
      to prepare and examine blood smear samples. 4. Ability to select and preserve
      microbiological samples for analysis, and to perform Gram staining analysis. 5.
      Ability to perform and evaluate pregnancy test. However, many other laboratory
      skill items are permitted in the model curriculum, as emphasized by the
      individual university. Therefore, reforms require appropriate changes in the
      educational programs for laboratory practice on the undergraduate level. In the
      Toyama Medical and Pharmaceutical University, all students must study compulsory
      fundamental laboratory technique in the first semester of the 5th year and, in
      addition, 6th graders in the last two months may choose an advanced clinical
      training course including genetic examinations. An important feature of our
      clinical training program is to introduce problem-based learning(PBL) tutorial
      education, which utilizes reversed CPC(R-CPC). An additional elective curriculum
      in clinical laboratory practice will be required, providing unique training
      programs based on student needs, the educational principles of each university
      and the specialties of the instructors.

PMID- 14653199
TI  - [Postgraduate medical training in laboratory medicine and clinical genetics in
      Chiba University Hospital].
AB  - Compulsory postgraduate clinical training in laboratory medicine will start on a
      national basis in April 2004. It remains to be discussed how departments of
      laboratory medicine and/or divisions of clinical laboratory should contribute to
      the training program. I here summarize what we are planning to do in Chiba
      University Hospital together with my personal views on this topic. Two points are
      of note in our program. First, one-week training in the division of clinical
      laboratory is essential as a part of the 6-month training of internal medicine.
      The items in the program include Gram staining, white blood cell differential
      counting, urinary sediment study, and representative point-of-care testing. A
      program to follow the entire flow of laboratory tests(from withdrawal of blood to
      reporting of the test results) is also included to highlight a variety of pre
      analytical errors. Furthermore, trainees are encouraged to learn how to work and
      co-operate with co-medical personnel. Second, our program aims at training
      postgraduate medical students to be clinical geneticists competent at genetic
      counseling. Genetic counseling is the process by which patients or relatives at
      risk of a disorder that may be hereditary are advised of the consequences of the
      disorder, the probability of developing or transmitting it and of the ways to
      test them. Thus, our final goal is to foster genetically oriented experts in
      laboratory medicine and clinical geneticists with a wide knowledge of laboratory
      medicine.

PMID- 14653200
TI  - [Laboratory medicine in the compulsory postgraduate clinical training system-
      newly revised program in Nihon University School of Medicine].
AB  - In 1999, the 4th report of the discussion group on 21st century medicine and
      health care proposed that it was necessary to establish in medical education a
      core curriculum emphasizing carefully selected basic content and to greatly
      expand the number of subjects that students might take electively. Following this
      report, a model core curriculum was made by the research and development project
      committee for medical educational programs in 2001. Similarly, the necessity of
      establishing a standardized postgraduate training curriculum and system has been
      discussed for many years. The Departments of Education and Technology and Welfare
      and Labor proposed a new curriculum named "Objectives in postgraduate clinical
      training" in order to ensure the quality of the medical doctors licensed to
      practice medicine in postgraduate clinical training in 2002. Following this new
      curriculum, Nihon University School of Medicine revised and enlarged its
      postgraduate program. All graduates are required to enter a full rotation program
      including general disciplines for two years. In addition to this basic
      curriculum, an elective curriculum will be added, providing attractive training
      programs based on medical trainees' needs. The training program in Laboratory
      Medicine is administered in the 2nd year as an elective program.

PMID- 14653201
TI  - [The clinical laboratory training after the graduate in local training hospital
      setting].
AB  - As clinical training has become a compulsory element of the training of
      physicians, all doctors are now required to undergo training in basic abilities
      of diagnosis and treatment. Clinical training has become possible in local
      medical organizations as well as university hospitals and large hospitals. There
      are full-time clinical pathologists in the laboratory staff of large hospitals,
      but they have little time for clinical trainees in the present educational system
      in the field of clinical laboratory. In mid-size and small hospitals, there is no
      clinical pathologist at the central diagnostic and treatment division, and
      clinical laboratory technicians are expected to play roles of trainers. It is
      important for the training administrator to prepare an environment in which
      clinical trainees can learn the selection of examinations, execution of
      examinations, interpretation of results, and actual handling of patients and,
      particularly in the execution of examinations, to cooperate with the director of
      the examination division and see that trainees can learn the necessary skills
      that they must acquire. The training administrator must also formulate a program
      to help clinical trainees to develop the abilities necessary for them to function
      as a member of team care. Such a program must not only be effective for the
      training of physicians but also contribute to the development of laboratory
      technicians and to improvements in the quality of medical care that is provided.

PMID- 14653202
TI  - [Intravenous myocardial contrast echocardiography; recent advances].
AB  - Until quite recently, contrast echocardiography for myocardial perfusion imaging
      has required the invasive direct injection of contrast agent into the coronary
      artery. Recent advances in ultrasonic technology and contrast agents have enabled
      myocardial contrast echocardiography with intra-venous injection of contrast
      agent in the clinical setting. This noninvasive technique has made the following
      clinical applications; left ventricular opacification, determination of the
      endocardium, enhancement of the Doppler flow signals, and detection of myocardial
      perfusion. Furthermore, in the near future, local drug delivery and pathology
      specific targeted adherence of contrast agent may be added to the applications
      for the treatment. Intravenous myocardial contrast echocardiography is expected
      to have wide-ranging clinical potential.

PMID- 14653203
TI  - [The monitoring of residual disease for chronic myelogenous leukemia patients
      treated with imatinib mesylate: detection of T315I mutation in ATP binding site
      of BCR/ABL gene].
AB  - Imatinib Mesylate, a specific inhibitor of BCR/ABL tyrosine kinase, was developed
      as a molecularly targeted drug for the treatment of patients with chronic
      myelogenous leukemia. We evaluated effectiveness of the drug on cytogenetic
      response for monitoring residual disease using fluorescence in situ
      hybridization(FISH), reverse transcription-nested-polymerase chain reaction(RT
      nested-PCR) and competitive PCR strategy. Of 9 patients in chronic phase, 7
      achieved major cytogenetic response(CR) and 2 achieved minor CR by FISH. In 3 out
      of 6 patients with complete CR, no BCR/ABL gene was detected by RT-nested-PCR in
      peripheral blood or bone marrow specimens. Of 4 patients in accelerated phase, 1
      achieved complete CR but 3 developed blast crisis. Despite high efficacy of
      Imatinib, 5 out of 13 patients showed resistance to the drug. To clarify the
      mechanism of resistance, we have newly developed a method for investigating a
      point mutation of T315I in tyrosine kinase domain of BCR/ABL gene using RT-PCR
      restriction digested analysis. None of them showed T315I mutation. The
      sensitivity of the method was as low as 10 copies of mutant gene. The method is
      useful for screening the mutation when there are many clinical samples or low
      copy number of BCR/ABL gene. BCR/ABL value obtained by FISH was of use to predict
      cytogenetic response when residual disease was above 2 to 3%. Below this level,
      the routine use of RT-nested-PCR was suffices to monitor minimal residual
      disease.

PMID- 14653204
TI  - [New diagnostic tests for rheumatoid arthritis].
AB  - Rheumatoid factor(RF) is one item in the classification criteria for rheumatoid
      arthritis(RA), with a tolerable sensitivity of 69.3% for RA but low specificity
      against other rheumatic diseases(76.4%). Anti-agalactosyl IgG antibody(CARF)
      showed a slightly higher sensitivity(72.0%) but the specificity was even
      lower(67.9%). Anti-cyclic citrullinated peptide antibody(anti-CCP), a new
      diagnostic test for RA, demonstrated higher sensitivity(76.0%) and
      specificity(91.5%), and the ROC analysis revealed the marked superiority of anti
      CCP to other markers(i.e. RF, CARF, and IgG-RF). Matrix metalloproteinase-3 (MMP
      3) showed a significantly positive correlation with CRP, suggesting it might be
      more useful for evaluation of RA activity and prediction of the prognosis of
      joint destruction. On the contrary, two combination assays, "MMP-3 or CARF" and
      "MMP-3 or anti-CCP", showed the highest sensitivity(86.7%) for RA. Similarly, in
      early RA the sensitivities of CARF, MMP-3 and anti-CCP were lower than in
      RA(66.7%, 66.7% and 58.3%, respectively), but the sensitivities of combination
      assays "MMP-3 or CARF" and "MMP-3 or anti-CCP" were 91.7% and 83.3%,
      respectively. Thus, we concluded that these combination assays are useful in the
      diagnosis of RA and detection of early RA.

PMID- 14653205
TI  - [Human germline genetic tests].
AB  - A guideline for genetic testing by 10 scientific societies was published
      recently. This can be summarized as follows. 1) Generalized medical care for
      genetic medicine is necessary when genetic testing is considered. 2) Analytical
      validity, clinical validity and clinical usefulness must be proven when genetic
      testing is applied to clinical medicine. 3) Informed consent must be given by the
      client before genetic testing is performed. 4) Information on an individual's
      genetic test must be protected tightly and should not be disclosed to others
      without permission from the client. 5) Genetic counseling must be performed
      before genetic testing is performed. 6) The purposes of genetic test performed to
      prepositus ((i) for definite diagnosis of the patient and (ii) for obtaining
      information by predictive tests for family members) should be clearly
      distinguished. 7) Genetic tests for detection of carrier status of specific
      genetic conditions should be carefully performed, because they do not affect the
      health condition themselves, but can be a cause of discrimination. 8) Predictive
      genetic tests must be performed very carefully, especially when no procedures of
      treatment/prevention are available. 9) In general, genetic testing of children
      should be considered when such tests provide clinical benefits to the children
      themselves.

PMID- 14653206
TI  - [Reference value and reference limits or cutoff value in clinical nutrition].

PMID- 14653207
TI  - [Practical uses of anthropometric reference date in the clinical nutrition].

PMID- 14653208
TI  - [Nutrition assessment by plasma protein].

PMID- 14653209
TI  - [Diagnosis of trace elements deficiency disease].

PMID- 14653210
TI  - [Evidence-based medicine (EBM) for assessment of vitamin deficiency].

PMID- 14653211
TI  - [Nutritive disorders (obesity and weight loss) caused by endocrine diseases].

PMID- 14653212
TI  - [Indirect calorimetry: a modality of nutritional assessment in critically ill
      patients].

PMID- 14653213
TI  - [Significance of nutritional assessment and its application in gastro-intestinal
      disease].

PMID- 14653214
TI  - [Laboratory data for assessment of nutrition in liver disease--with special
      reference to alcoholic hepatitis and nonalcoholic steatohepatitis (NASH)].

PMID- 14653215
TI  - [Nutritional management in cardiovascular diseases].

PMID- 14653216
TI  - [Diabetes mellitus and related nutritional examination].

PMID- 14653217
TI  - [Obesity as a disease and nutritional examination].

PMID- 14653218
TI  - [The method of utilizing food allergy test].

PMID- 14653219
TI  - [Hyperlipemia and nutritional examination].

PMID- 14653220
TI  - [Nutritional examinations for kidney diseases].

PMID- 14653221
TI  - [Nutrition assessment for pressure sores--importance of trace element].

PMID- 14653222
TI  - [Relationship between hematological disorder and laboratory medicine].

PMID- 14653223
TI  - [Infectious diseases attended by dietitian].

PMID- 14653224
TI  - [Effects of sigma receptor ligands on psychiatric disorders].
AB  - It has recently been suggested that sigma receptors are involved in psychiatric
      disorders. Sigma 1 receptor antagonists are effective in animal models of
      positive symptoms, cognitive deficit and disruption of prepulse inhibition in
      schizophrenia. They also inhibit the development and expression of the
      conditioned place preference induced by cocaine. On the other hand, sigma 1
      receptor agonists reduce the immobility time in the forced swimming and tail
      suspension tests. Furthermore, sigma 1 receptor agonists attenuate the
      conditioned fear stress (CFS) response (which is not attenuated by typical
      anxiolytics or antidepressants) in rodents. The attenuating effects are mediated
      through sigma 1 receptors, which are closely related to the mesolimbic
      dopaminergic systems. Sigma 1 receptor agonists also have anti-amnesic effects in
      various experimental models. Neurosteroids such as dehydroepiandrosterone sulfate
      and pregnenolone sulfate attenuate the CFS response and have anti-amnesic
      effects, the effects being mediated via sigma 1 receptors. These findings suggest
      that sigma receptors are novel potential targets for the treatment of psychiatric
      disorders such as schizophrenia, drug abuse, depression and dementia.

PMID- 14653225
TI  - [Psychiatric disorders and neural mechanisms underlying energy intake and
      expenditure: a review].
AB  - Anorexia is one of the common symptoms caused by various psychiatric disorders.
      Increasing evidence indicates that neuroleptics can induce weight gain, obesity,
      and diabetes mellitus. However, the mechanisms underlying these conditions have
      not been fully elucidated. In this review, we describe molecular neuroanatomic
      aspects of current biology of energy homeostasis that would help to address the
      psychiatric issues noted above, focusing on the central leptin/melanocortin
      system. An adipocyte-derived hormone, leptin acts on the arcuate hypothalamic
      nucleus (Arc) to inhibit feeding behavior and simultaneously to promote energy
      expenditure. Leptin activates Arc neurons producing alpha-melanocyte-stimulating
      hormone (alpha-MSH) and inhibits those producing agouti-related protein (AgRP).
      alpha-MSH is an endogenous agonist for the melanocortin-4 receptor (MC4-R) that
      is expressed exclusively in the central nervous system (CNS), whereas AgRP acts
      as a MC4-R antagonist. It is also established that MC4-R blockade produces an
      over-eating/obesity syndrome in rodents and humans. Thus, MC4-R-expressing
      neurons are downstream targets of leptin. Of interest, MC4-R-positive neurons
      densely populate in CNS sites critical for energy homeostasis and associated with
      psychiatric disorders, including the paraventricular hypothalamic nucleus and
      central amygdaloid nucleus. In addition, Arc alpha-MSH neurons receive
      serotonergic inputs from raphe neurons. Finally, an AgRP gene polymorphism has
      been associated with anorexia nervosa. These findings suggest that the central
      melanocortin system is a target for psychiatry.

PMID- 14653226
TI  - Effects of foods on the pharmacokinetics and clinical efficacy of quazepam.
AB  - The effects of foods on the pharmacokinetics and clinical efficacy of quazepam, a
      benzodiazepine derivative, in healthy persons were examined. Six healthy Japanese
      male subjects were randomly divided into three groups and each subject was
      treated with quazepam under the following three conditions by the crossover
      method. For the fasting state, subjects were administered 15 mg quazepam 11 hours
      after a meal. For the postprandial state, subjects were administered 15 mg or 30
      mg quazepam 2 hours after a meal. Mean peak plasma concentration (Cmax) of
      quazepam was significantly higher [1.6-2.8 fold] with administration 2 hours
      after a meal than 11 hours after a meal. However, in regard to 15 mg of quazepam
      administration, the area under the curve (AUC) did not differ between
      administration 2 hours after a meal and 11 hours after a meal. In addition,
      differences were observed neither in other pharmacokinetic parameters or blood
      metabolite concentration under all of the study conditions, nor in clinical
      evaluation of subjective symptoms, complete blood count, or biochemical analyses
      between administrations 2 and 11 hrs after a meal. The present study showed that
      administration 2 hours after a meal did not affect subjective symptoms or
      physical functions so much; therefore it suggested favorable tolerance of this
      drug. However, it was also suggested that, in actual clinical use, it is
      important to evaluate the physical function including measurements of vital signs
      and hematological test results, carefully considering the effects of foods and
      daily life-style.

PMID- 14653227
TI  - [Cognition impairment in the klotho gene mutant mice and oxidative stress].
AB  - Klotho is a recently identified gene that is a very different type from those
      involved in previously described premature-aging syndromes and cell senescence.
      Although a high level of expression of the klotho gene was detected in the kidney
      and brain, little is known about the function of the klotho gene in the brain.
      Here we investigated the changes in mnemonic function accompanying aging in
      klotho mutant mice. Cognitive function measured by novel-object recognition and
      conditioned-fear tests in klotho mutant mice was normal at the age of 6 weeks,
      but markedly impaired at the age of 7 weeks. Lipid peroxide (malondialdehyde) and
      DNA peroxide (8-hydroxy-2'-deoxyguanosine) levels in the hippocampus of klotho
      mutant mice increased at the age of 5 weeks, 2 weeks prior to the development of
      cognition deficits. Pro-death Bax increased, while anti-death Bcl-2 and Bcl-XL
      decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of
      klotho mutant mice at the age of 7 weeks. A potent antioxidant alpha-tocopherol
      prevented the cognition impairment and lipid peroxide accumulation, and decreased
      the number of apoptotic cells in klotho mutant mice. These results suggest that
      oxidative stress has a crucial role in the aging-associated cognition impairment
      in klotho mutant mice. Klotho protein may be involved in the regulation of
      antioxidative defense.

PMID- 14653228
TI  - [Does electroencephalogram finding become a predictor of lithium response in
      bipolar disorder?].
AB  - To prescribe lithium appropriately to bipolar patients, detecting clinical
      predictors of lithium response in bipolar disorder is important. Considering all
      mood stabilizers except lithium are anticonvulsants, there may be some
      relationship between lithium response and EEG abnormalities. The present paper
      reviews the electroencephalogram finding as a possible predictor of lithium
      response.

PMID- 14653229
TI  - [Project. Therapy of acid-dependent diseases. First Moscow Agreement, February 5,
      2003].

PMID- 14653230
TI  - [Psychophysiologic disorders in patients with functional disorders of upper
      sections of the gastrointestinal tract and with gastroesophageal reflux disease].
AB  - The features of the psychovegetative status in patients with functional disorders
      of the esophagus and stomach (FD) and gastroesophageal reflux disease (GERD) are
      investigated. The methods included clinical, instrumental and psychometric
      examination. The patients of both groups had similar vegetative abnormalities and
      a tendency towards the growth of depression and anxiety parameters, did not
      differ in psychosocial factors, and had a wide range of psychovegetative
      abnormalities (PA). Lump in the throat, heartburn, epigastralgia (p < 0.01),
      depression, actual anxiety, alexitymia and vegetative disorders decreased in both
      groups (p < 0.05) after treatment with citalopram (20 mg per day) during 2
      months. So PA are revealed in patients with FD and GERD, and citalopram reduces
      psychovegetative and GIT disorders.

PMID- 14653231
TI  - [Atropine resistance and hypersensitivity as signs of gastric autonomic
      regulation in peptic ulcer].

PMID- 14653232
TI  - [Features of peptic ulcer with concomitant bronchial asthma in the elderly].
AB  - The purpose of the study was to examine particular features of the clinical
      course of stomach ulcer (SU) and duodenal ulcer (DU) in conjunction with
      bronchial asthma (BA) in elder patients. We examined 59 patients with BA in
      conjunction with SU and DU at the age of 69-89 (46 males and 13 females). All
      patients underwent esophagogastroduodenoscopy (EGDS) and H. pylori examination of
      tissue samplings from the mucous coat of the stomach and duodenum (urease test).
      BA was diagnosed based on the clinical picture, examination of the external
      respiration function, reversibility of bronchial obstruction of not less than 20%
      after the pharmacological test or anti-inflammatory treatment.

PMID- 14653233
TI  - [Pathogenetic features of recurrent peptic ulcer in the elderly].

PMID- 14653234
TI  - [Microflora of the gastroduodenal zone and morphological characteristics of
      phases of recurrent peptic ulcer].
AB  - The studies conducted for 126 patients with stomach and duodenal ulcers revealed
      that at the acute state of recurrent ulcer activation of the microflora
      displaying pathogenetic signs and corresponding to the third or fourth degree of
      dysbacteriosis takes place in the ulcerous defect zone along with
      microcirculatory disorders, necrotic inflammatory processes and reduction of the
      lysozyme content in tissues. This allows comparing ulcers of the gastroduodenal
      zone to an infected wound. At the sub-acute phase of recurrent ulcer (next one or
      two weeks) microbiological changes in the per-ulcer zone reduce to dysbacteriosis
      of the second or third degree as inflammatory and necrotic processes cease, an at
      the phase of cicatrisation and epithelization they are similar to normal
      biocenosis.

PMID- 14653235
TI  - [Antisecretory therapy for prevention of stenoses of bougienage after-burn of
      esophageal strictures].
AB  - The purpose of the research was to study the efficacy of the bougienage of after
      burn esophageal strictures against the background of long-term treatment with
      proton pump inhibitors of H2-blockers. 100 patients with after-burn esophageal
      strictures were divided into 3 groups in a random way: 1) only bougienage--53
      patients; 2) bougienage and omeprazole, 20 mg per day during 12 months--20
      patients; 3) bougienage and ranitidine, 300 mg per day during 12 months--27
      patients. Bougienage was efficient in 83 patients (83%). 17 patients underwent
      esophagoplasty due to inefficiency of bougienage. Repeated bougienage was
      necessary for 35% of patients who were taking omeprazole (p = 0.04), 48.1%-
      ranitidine (p = 0.2), and 60.4% of patients who underwent only bougienage.
      Bougienage of the esophagus is efficient in treatment of after-burn strictures.
      Twelve-month treatment of these patients with omeprazole reduces the number of
      repeated bougienage courses significantly.

PMID- 14653236
TI  - [Chronic gastritis in children with concomitant diseases of the thyroid gland].
AB  - We examined: 1 group--16 children with chronic gastritis (CG) and autoimmune
      thyroiditis (AT); 2 group--41 children with functional thyroidal pathologies; 3
      group--23 children with CG only. The average age in all groups was 11.17 +/-
      2.98. HP (68%) was revealed equally frequently in all the groups. Antibodies to
      H+/K(+)-ATPase of parietal cells were revealed in the first and second groups
      only (31-36%), p < 0.05 as compared to the third group. CG of the stomach body
      was more frequently revealed in the first group using endoscopic and histological
      tests. The second group had more frequent and more apparent lesions of the antral
      part. Thus, in case of concomitant diseases of the thyroid gland CG has an
      autoimmune nature of an inflammation of the mucous coat of the stomach.

PMID- 14653237
TI  - [Pathogenetic basis of the application of calcium antagonists in the treatment of
      recurrent peptic ulcer].
AB  - Examination of 150 ulcer patients determined that the exacerbation of the disease
      proceeds against the background of essential augmentation of calcium in the
      blood, which is most expressed at the acute phase of relapse, at the localization
      of ulcer in the duodenum, in men of young age. This is accompanied by the rising
      production of hydrochloric acid and pepsinogen, decrease of production of
      gastromucoproteins, hypermotor dyskinesia of stomach, hypocoagulation,
      infringement of microcirculation in the mucous coat of the gastroduodenal zone
      displayed as microthromboses, plasmorrhagias, hemorrhages. The inclusion of the
      calcium antagonist Corinfarum in the complex therapy reliably accelerates the
      liquidation of signs of relapse, reduces terms, increases the percentage of ulcer
      cicatrisation, and promotes normalization of stomach functions, calcium balance,
      hemostasis and microcirculation.

PMID- 14653238
TI  - [Laser therapy and famotidine in complex restorative treatment of primary chronic
      gastroduodenitis].
AB  - Primary chronic gastroduodenitis (PCG) is one of the most frequent diseases of
      the gastrointestinal tract. Timely and efficient treatment of patients with PCG
      promotes ulcer prevention. In this connection, an urgent problem of restorative
      medicine is to develop medical programs with active introduction of
      pharmacophysiotherapeutic complexes, in particular, laser therapy and anti
      secretory preparation (famotidine) that increase therapeutic efficacy of
      treatment of this disease. To this end, we give results of treatment of 50
      patients with primary chronic gastroduodenitis (26 having undergone laser therapy
      only, and 24 having had a combination of laser therapy and famotidine), which
      demonstrated that the complex action method has a more adequate effect on
      pathogenetic components in this disease than monotherapy.

PMID- 14653239
TI  - [Oxidase activity of ceruloplasmin and the state of hemocoagulation in patients
      with chronic pancreatitis].
AB  - We examined oxidase activity of ceruloplasmin, fibrinogen content in the blood
      serum and the state of hemocoagulation in 80 patients with chronic pancreatitis
      of different etiology. The presence of ceruloplasmin was considered to be
      paraphenylenediamine oxidase. It was shown that at the acute stage of the disease
      oxidase activity of ceruloplasmin is increased and depends on the severity,
      duration and presence of complications. An increase of the anti-oxidant action
      protein content is accompanied by hypercoagulation and an increase of the
      fibrinogen content. Data are given on the availability of correlation
      relationship between the fibrinogen content and general blood coagulation
      constant.

PMID- 14653240
TI  - [Dynamics of clinical symptoms, indices of quality of life, and the state of
      motor function of the esophagus and rectum in patients with functional dyspepsia
      and irritable bowel syndrome after Helicobacter pylori eradication].
AB  - 94 patients with irritable bowel syndrome and functional dyspepsia were included
      in the study. To confirm the diagnosis of H. pylori infection, all patients
      underwent fibroesophagogastroduodenoscopy with histological and urea tests before
      and 5 weeks after treatment. Standard eradication was performed. 25 patients
      underwent intraesophageal and anorectal manometry using the Polygraf device,
      Sweden. The dynamics of clinical symptoms, life quality (SF-36), manometry data
      and data of the histological examination of the stomach mucous coat was assessed.
      63.5% of patients had clinical improvements following the eradication. The
      threshold of rectal sensitivity rose in 40% of patients. The esophageal motor
      function normalized in 48% of patients. An improvement of the morphological
      picture of chronic gastritis was recorded in 58.7% of patients.

PMID- 14653241
TI  - [Clinical significance of studies of microorganisms of the intestinal mucosa by
      culture biochemical methods and mass fragmentography].
AB  - This research is a continuation of the series of studies of the parietal
      microbiota of the bowel tissue samplings by the gas chromatography and mass
      spectrometry (GCMS) method [G.A. Ossipov et al.//Journal of the Society of
      Russian Gastroenterologists, 2001, 1:54-69]. The purpose was to study a number of
      new microorganisms in view of new data on the composition of their fatty acids
      (FA) and aldehydes; to confirm the presence of a number of bacteria, fungi and
      aerobic actinomycetes revealed earlier by FA markers in the composition of the
      bowel parietal microbiota by their isolation in a pure culture; to amend the
      estimation of the clinical value of changes in the composition of the human bowel
      parietal microflora in case of irritable bowel syndrome (IBS) and antibiotics
      associated diarrhea (AAD). We examined 31 patients with IBS with predominating
      diarrhea, 18 patients with AAD and 3 volunteers (a control group). We studied the
      blood samples, tissue samplings of the mucous coat of the jejunum, ileum and
      colon and composition of healthy people's feces. The GCMS method was applied.
      Morphology of defined strains was controlled by methods of light and scanning
      electron microscopy. We found a substantial portion of eubacteria among the bowel
      microorganisms and specific changes of their species in case of IBS and AAD.
      Taking into account their physiological and biochemical activity, when regulating
      their concentration one can expect at least the same effect as when regulating
      the number of bifidobacteria and lactobacilli in treatment of intestinal
      pathologies and other diseases related to bowel dysbacteriosis. The analysis of
      the feces microbiota using the GCMS method by FA of parietal microorganisms
      provides reliable data on their number both in feces and in tissue samplings. We
      found a substantial portion of eubacteria among other bowel microorganisms (27%
      in the jejunum and 16% in the colon) and specific changes of their species in
      case of IBS and AAD. The concentration of streptomycetes, rhodococci and other
      members of the Actinomycetales order becomes dozens times more and/or reduces in
      pathological states. The tenfold concentration of markers of lactobacilli and
      bifidobacteria in some diseases stimulates the differentiated application of
      widespread probiotics based on these bacteria.

PMID- 14653242
TI  - [Comparative characteristics of lipid components of gallbladder and liver bile
      fractions in children with chronic cholecystitis].
AB  - In the course of this research we studied indices of lipid components--neutral
      lipids, phospholipids of biliary and fatty acids--and made their comparative
      assessment in the cystic and hepatic bile fractions in 25 children with chronic
      cholecystitis (CC). Chronic cholecystitis is characterized by dislipoproteinemia
      in the cystic and hepatic bile fractions, which is displayed as a reduction of
      the level of tauroacids and augmentation of glycocholic acid at a simultaneous
      increase in levels of primary and secondary biliary acids, as an increase in the
      ratio of levels of free fatty acids and cholesterol esters (CE) against the
      background of the decreasing number of monoglycerides and CE; as an increase in
      the ratio of levels of lysophosphatidylcholine (lysoPTC) and phosphatidylcholine
      against the background of augmentation of lysoPTC and phosphatidylethanolamine;
      as augmentation of polyene fatty acids in the composition of general lipid bile
      fractions. It is assumed that the obtained results can be used as indices of
      efficacy of drugs and non-medicinal preparations prescribed with the purpose of
      correction of lipid metabolic imbalances in case of chronic cholecystitis in
      children.

PMID- 14653243
TI  - [Possible treatment with immune system modulators of patients with pathology of
      the digestive organs. Informational letter].

PMID- 14653245
TI  - [Mucocele of the vermiform appendix].

PMID- 14653244
TI  - [Experience with the application of the preparation nexium in patients by using
      the BioEnterics Intragastgric Balloon].

PMID- 14653246
TI  - [Late results of portacaval surgical shunt in patients with extrahepatic portal
      hypertension].
AB  - Late outcomes of portocaval shunting (PCS) were analyzed in 135 patients with
      extrahepatic portal hypertension (EPH). It was established that the methods of
      choice in such patients should be splenorenal anastomosis, mesentericocaval
      anastomosis (MCA) "side by side" and H-type with autovenous or synthetic
      insertions. The best results were detected in a combination of portocaval
      anastomosis with the suturing pf stomach and esophageal varicose veins, if the
      diameter of the anastomosed vessel was small and portal pressure was reduced by
      less than 25% (100 mm of water column). The ineffectiveness of MCA "end in side"
      by Bogoras and cavamesenterial anastomosis was shown due to low efficiency and
      severe complications, respectively. These data demonstrate efficacy of
      endovascular dilatation in PCA stenoses, yet the possibilities of severe
      complications still exist. The best result of endoscopic PCS estimation 1 year
      after the surgery suggested complete recovery of patients with EPH in most cases.

PMID- 14653247
TI  - [Bioelectrical activity and evacuation function of the gastric stump in an early
      period after different means of gastric resection and variations in the formation
      of anastomoses].
AB  - The results of the stomach resection on the occasion of stomach and duodenal
      ulcer were analyzed. Bioelectric activity of the stomach stump was studied in a
      comparative aspect, and early recovery of the motor function of the resected
      stomach after the formation of pyloroimitating gastroduodenal anastomoses was
      shown. Revealed roentgenologic mechanisms of the evacuator function of the
      stomach stump let us determine evacuation types for the early postoperative
      period. The formation of pyloroimitating gastroduodenal anastomoses is
      functionally advantageous.

PMID- 14653248
TI  - [Semax and some glyproline peptides accelerate the healing of acetic ulcers in
      rats].
AB  - Previously we showed that peptides PGP, PG, GP and semax have protective anti
      ulcer properties using different models of ulcerogenesis. Semax (MEHFPGP) is a
      nootropic analogue of adrenocorticotropin 4-7 stabilized by PGP in the C-terminal
      region. In this study we examined the impact of these peptides on the development
      and healing of acetic ulcers in rats. The histomorphological and dynamical
      characteristics of acetic ulcers are most similar to human chronic ulcers. All
      the peptides were shown to accelerate the process of ulcer cicatrisation in a
      varying degree (GP semax PG PGP). The dynamics of structural changes in the place
      of ulcer formation investigated with the use of cytohistological control
      demonstrated that their anti-ulcer effects can be related to their ability to
      accelerate ulcer clarification from necrotic tissues and to activate the process
      of cicatrisation and epithelization. PGP and GP were also shown to reduce the
      inflammation in the ulcer zone on the fifth day after acetic acid application.

PMID- 14653249
TI  - [Biliary pathology in patients infected with hepatitis viruses G and TT].

PMID- 14653250
TI  - [Experimental validation of regeneration therapy in hepatitis caused by toxic
      medication].

PMID- 14653251
TI  - Patient controlled analgesia. Pushing for safe pain relief.

PMID- 14653252
TI  - Recent onset neurofibromatosis complicating eclampsia with maternal death: a case
      report.
AB  - Neurofibromatosis in pregnancy has been associated with poor perinatal outcome. A
      30-year-old multigravida developed peripheral lesions of neurofibromatosis during
      the third month of pregnancy. She had eclampsia complicated with fatal left-sided
      massive intracerebral haemorrhage detected on computed tomography at 8.5 months
      gestation. Investigations were suggestive of HELLP syndrome. A still-born male
      baby was delivered. In spite of all supportive measures the patient died on the
      third postpartum day. We conclude that recent onset neurofibromatosis in current
      pregnancy should be considered as a predictor of potentially adverse maternal and
      fetal outcome and such pregnancies be managed in tertiary level referral centre.

PMID- 14653253
TI  - Successful revascularization of a long chronic total occlusion of the right
      coronary artery utilizing the frontrunner X39 CTO catheter system.

PMID- 14653255
TI  - Telemedicine.

PMID- 14653254
TI  - Minimally invasive total hip arthroplasty.

PMID- 14653257
TI  - Drugstore memories. American pharmacists recall life behind the counter (1824
      1933).

PMID- 14653256
TI  - Early diagnosis of Usher Syndrome Type 1 now possible.

PMID- 14653261
TI  - "Nursing by default": the evolution of floor nursing, 1900-1965.
AB  - Today, as we witness an ever increasing trend toward specialization within acute
      care medical centers, as well as the fragmentation of care in the outpatient
      setting, it is interesting to note the history of nursing within hospitals. This
      brief article provides us with a glimpse of the history of "floor nursing" - a
      term that has been consistently used to describe the care provided by thousands
      of nurses during the past century

PMID- 14653263
TI  - The nurse habitue: the history of addiction in nurses, 1850-1982.

PMID- 14653264
TI  - Carl Pfaffmann: 27 May 1913 - 16 April 1994.

PMID- 14653265
TI  - The quality and comparability of child care data in U.S. surveys.
AB  - This paper examines the quality and comparability of child care data obtained
      from eight waves of data from four nationally representative data sources: the
      National Longitudinal Survey of Youth (1986 and 1988), the Survey of Income and
      Program Participation (1986, 1987, 1988, and 1990), the National Child Care
      Survey, and the National Survey of Families and Households. We examine whether
      different study designs and survey techniques for asking questions about child
      care produce similar results on both the levels and determinants of child care.
      We identified four main sources of difference in the data sets that could impact
      the quality and comparability of child care research: when the interview is
      conducted; screening questions used to determine who is asked about child care;
      the population of parents and children represented in the survey; and the way
      child care questions are asked. Our findings indicate that summer interviews and
      screening on mother's work status produce the largest differences in the levels
      and effects of child care across these studies. Even after removing the effects
      of summer interviews and screening questions, however, substantial differences
      exist across the studies.

PMID- 14653266
TI  - Chance of a lifetime. Interview by Ann Luck.

PMID- 14653267
TI  - Effecting change in the path of a rhinoceros herd.

PMID- 14653268
TI  - [Nicolas Houel and Michel Dusseau, apothecaries of the XVIth century in Paris].
AB  - These two apothecaries of the XVIth century of Pharmacy in Paris were outstanding
      personalities. Nicolas Houel founded a charity in the south of Paris at Saint
      Marcel suburb: The House of Christian Charity. It was a philanthropic
      organization composed of a chapel, an orphanage, a hospital, an apothecary's shop
      and a medicinal plants garden called Le Jardin des apothicaires. This institution
      is at the origin of the future Paris Pharmacy College (1777) and of the Paris
      School of Pharmacy (1803). This apothecary was also an artist, a poet, the author
      of artistic and scientific works. He wrote three pharmaceutical books between
      1571 and 1573. The first one Pharmaceutices libri duo is about laxative and
      purgative medicines in accordance with Mesue's concepts, the second is a Plague
      Treatise and the third a Theriac and Mithridat Treatise. Michel Dusseau is the
      author of the first pharmaceutical book written in French prose. It was published
      in Lyon in 1561: l'Enchirid ou Manipul des miropoles. The life of Michel Dusseau
      had remained quite unknown but we recently managed to identify four generations
      of Dusseaus: Christofle, the ancestor, who lived in the XVth century and was not
      an apothecary, Michel a juror of the Paris apothecaries community and the author
      of the Enchirid, Pierre, Michel's son, also an apothecary, and lastly, Pierre's
      children who were the 4th generation. L'Enchirid is a "Manual for myrrh sellers
      ", a galenic pharmacy book divided into three parts. The first part shows how to
      prepare medicines, the second deals with pharmaceutical operations, the third is
      dedicated to the preparations of galenic forms. This book was well appreciated by
      French apothecaries in the XVIth-XVIIth centuries but sank into oblivion because
      of obsolescence.

PMID- 14653269
TI  - [The difficult history of first french national Codex].
AB  - The first national Codex appeared in 1818. It was written in latin, and its
      french translation was published at the end of 1819. The Journal de pharmacie et
      des sciences accessoires, published by the Societe de pharmacie de Paris, blamed
      on several occasions and in a very hard fashion some of its contents and
      specially the conditions of its publication. An action was brought against the
      private publisher of the Codex. The second edition of the Codex will be published
      only in 1837, in a deeply corrected form.

PMID- 14653270
TI  - [Latin and the training of apothecaries in France].
AB  - Reading pharmacopoeias and prescriptions, redacted in this degenerated latin
      which was the language of science, required a sufficient knowledge of that
      language. A study of the statutes of apothecaries' communities, is a good method
      to evaluate the role of latin in the training of apothecaries. These statutes
      could be divided into four groups: statutes redacted in latin, statutes redacted
      in french, but mentioning that latin was used for the examinations, statutes
      which mention a control of the capacity of the candidates to understand latin,
      statutes which do not mention latin. Some examples show the reality of latin
      knowledge. During the XVIth century, apothecaries used to travel to foreign
      counties in order to improve their knowledge. They had not to learn the language
      of the country, because masters and students used to speak latin. Young Balthazar
      Hummel, from Basel, went to Montpellier, in the house of the apothecary, Laurent
      Catelan, and never had to learn french, because he used only latin. During the
      XVIIIth century, apothecaries of Hotel-Dieu, a hospital in Rouen, were reunited
      after a competitive examination. On friday May 15th 1722, two candidates, Pierre
      Lechandelier and Michel Delaisement, had to answer in latin to the questions of
      the members of the jury. One of them, Lechandelier said that be was not able to
      do so in latin. He was then told that it was the rule and that he was not allowed
      to continue the examination. Delaisement answered to the questions in very good
      latin and became the apothecary of the hospital. His study shows that latin
      knowledge was required for apothecaries, even if differences appeared between the
      various french towns. So far as pharmacopoeias were concerned, an evolution took
      place at the end of the XVIIth century, Charas and Lemery wrote their famous
      books in french. But until 1818, the official pharmakopoeias were redacted in
      latin, which was still required for the training of apothecaries.

PMID- 14653271
TI  - [Hippiatric formularies established during the period of the Revolution].
AB  - Two hippiatric formularies established during the period of the Revolution are
      presented. The first one published in 1793, is a printed pamphlet of 8 pages,
      containing 68 drugs. The second one dated of january 1794 includes 26 items only,
      and consists in a unique chart entitled: Nomenclature des Drogues necessaires au
      traitement des maladies internes et externes des chevaux malades qui sont aux
      armees et dans les differents depots de la Republique. This is of particular and
      new interest when it tentatively synthesizes and standardizes the main
      pharmaceutical products able of fighting farcy and glanders. After the first work
      carried out by Bourgelat around 1760, it confirms the necessity of reforming the
      ancient and often useless polypharmacy, by selecting efficient drugs and in
      advising about their relevant use.

PMID- 14653272
TI  - [Benoit Mure, missionary of homeopathy in XIXth century].
AB  - Benoit Mure, born in Lyon the 4th of May 1809, was one of the most important
      person who spreaded the homeopathic medicine in the XIXth century, especially in
      Italy. Homeopathy is a therapeutic method which was founded by Christian Samuel
      Hahnemann, born in 1755 in Meissen. Benoit Mure, as he was ill, consulted an
      homeopathic doctor: Dr Sebastien Des Guidi, who cured him. From this time, he
      consacrated his whole life and personal fortune to spread homeopathy. In 1837 he
      created a dispensary in Palermo that will become further the "Royal Academy of
      Homeopathic Medicine". In 1839, he founded the dispensary of rue de la Harpe in
      Paris and teached homeopathy to many doctors. He spreaded also homeopathy in
      Brazil, then in Egypt. He died the 4th of March, 1858 in Cairo.

PMID- 14653273
TI  - [Nancy medicines for hospices and prisons in 1805].
AB  - The chemist Francois Mandel, past author of Pharmcopee de Nancy, writes a list of
      medicines for civil hospices and a formulary for prisons. To take care of these
      adult, poor sick, drugs and medicines are chosen simple, at little expense, but
      adequate to treat everyday diseases. The prison formulary holds many novel
      preparations. The two manuscripts have never been published.

PMID- 14653274
TI  - [Monastery garden, mystical garden].
AB  - The monastery garden is a symbolic place where medicinal plants have both
      therapeutic use and religious meaning. The cloister is a natural as well as a
      spiritual space, where the monastic virtues are expressed by the geometry of the
      alleys and the floral composition. By the end of the Middle Ages, a couple of
      abbeys designed enclosed gardens (hortus conclusus) to symbolize the Garden of
      Mary, often represented in 14th and 15th centuries paintings.

PMID- 14653275
TI  - [The apothicary of the "Maison Royale de Saint-Cyr"].
AB  - The "Maison Royale de Saint-Cyr", a royal school for education of poor noble
      officer's girls, founded by Louis XIV and Mme de Maintenon and working from 1686
      to the French Revolution, had an apothicary run by nuns. Its inventory has
      reached us and its fully and distinct contents well call to mind a 18th century's
      pharmacy with a large variety of tools for pharmaceutical and chemical
      preparations, set of furnitures and library. In the garden, a place, carefully
      cultivated, was reserved to medicinal plants for supply of the apothicary.

PMID- 14653276
TI  - Nitric oxide's role in heart failure: pathophysiology and treatment.
      Introduction.

PMID- 14653277
TI  - Autism caused by dental amalgam?

PMID- 14653278
TI  - Patient preference: conventional rotary handpieces or air abrasion for cavity
      preparation.
AB  - It has been suggested that patients should accept the use of the air abrasion
      technique over the conventional handpiece due to the reduced need for anesthesia.
      Technologies for both air abrasion and the conventional rotary handpiece have, in
      recent decades, seen major improvements, but there are no recent scientific
      publications that evaluate the patient's preference for these two technologies
      when performing a cavity preparation. This study determined the patient's
      preference for air abrasion or the rotary handpiece for removing occlusal fissure
      carious lesions in mandibular premolars. Ten healthy subjects 18 years of age or
      older were recruited from the General Dentistry Clinic of the University of
      Rochester Eastman Dental Center, with fissure caries at a DEJ depth of similar
      size (determined by radiographs and clinical examination) in any two mandibular
      premolars in opposite quadrants. Within each subject, the two methods of caries
      removal were randomly assigned. In one premolar, air abrasion was used for cavity
      preparation, and in the other premolar, a conventional rotary handpiece was used.
      At each visit prior to treatment, the patients were instructed to complete the
      Emotional Status (ES) questionnaire (SUNY University at Buffalo Craniofacial Pain
      Clinic) to assess differences in their emotional status between appointments. At
      each appointment, when the restorative treatment was completed, patients were
      instructed to rate their pain on the Visual Analogue Scale (VAS). A technique
      preference questionnaire was given after the second appointment. The subjects
      rated the perception of pain as significantly lower (p < 0.05) when using air
      abrasion (6.0 mm versus 29.6 mm). All of the patients preferred air abrasion over
      conventional rotary handpieces. None of the patients required anesthesia and
      there was no indication that the emotional status influenced the result. Air
      abrasion was the preferred method of cavity preparation when removing fissural
      caries in mandibular premolars and most subjects did not experience any pain when
      air abrasion was used.

PMID- 14653279
TI  - Comparison of different DIAGNOdent cut-off limits for in vivo detection of
      occlusal caries.
AB  - This study tested recently recommended cut-off limits for the laser fluorescence
      based device DIAGNOdent (KaVo) for detection of occlusal caries. Two hundred and
      forty-eight permanent molars from 94 patients (mean age 19.2 years) of a general
      dental practice were included. After professional tooth cleaning, the teeth were
      examined visually and by the laser fluorescence method. The extent of occlusal
      lesions (gold standard) was determined after minimal operative intervention. Upon
      fissure opening, 24 teeth had enamel caries and 224 teeth revealed dentin caries,
      of which 58 and 166, respectively, were up to or beyond half the dentin. The
      optimal cut-off limits based on the highest kappa-values (0.51 and 0.54) were >
      18 for superficial dentinal caries (D3) and > 37 for deep dentinal caries (D4).
      The comparison with DIAGNOdent cut-offs given by the manufacturer (n = 4) and
      those based on clinical trials with in vivo validation (n = 4) and in vitro
      studies with histological validation (n = 3) revealed a considerable variation in
      performance. Recommended cut-offs between 17 and 21 for superficial dentin
      lesions were in the same order of magnitude (0.48-0.51). On the D4 level, only
      the manufacturer's cut-off of > 34 achieved the best performance (0.51).
      According to the highest kappa-values and the area under the ROC curves (D3: A(z)
      = 0.903; D4: A(z) = 0.830), the agreement between the extent of validated caries
      and laser fluorescence value is still unsatisfactory.

PMID- 14653280
TI  - Failure risk of posterior composites with post-operative sensitivity.
AB  - Post-operative sensitivity (POS) may be observed in recently placed posterior
      composites. Evidence-based guidelines for the management of posterior composites
      with POS have yet to be determined. This study examined a retrospective analysis
      of the findings of a unique multi-center clinical trial to investigate the five
      year risk of failure of posterior composites with POS and to determine the
      factors likely to have an important impact on the prognosis of the restorations.
      Longitudinal five-year data from the multi-center trial of Occlusin were
      analyzed. Data pertaining to a total of 1,101 restorations were included in the
      study. The failure rate at five years was calculated by means of three selected
      methods for all the restorations included in the study and for restorations with
      POS. Risk of failure for restorations with POS was analyzed by calculating an
      odds ratio along with the 95% confidence interval (CI). Logistic regression was
      carried out in order to identify those factors most likely to have had an
      important impact on the prognosis of restorations with POS. The analysis revealed
      that the restorations of Occlusin with POS were found to have been more likely to
      have failed at five years than the restorations of Occlusin without POS, with
      odds ratios ranging from 1.73 (95% CI: 1.04, 2.87) to 1.97 (95% CI: 1.36, 2.85).
      Distributions of patient age and cavity size were significantly different for
      successful and failed restorations (chi-square test, p < 0.05). Logistic
      regression indicated that cavity size was the only factor likely to have
      influenced the prognosis of the restorations with POS (p = 0.041, odds ratio
      3.21, 95% CI 1.05: 9.70). Restorations with POS in large cavities were more
      likely to have failed by five years than restorations in small cavities. It was
      concluded that the restorations with Occlusin included in the Occlusin trial
      program were more likely to have failed at five years if POS occurred within one
      month of placement. Cavity size has been shown to have been an important factor
      in the prognosis of Occlusin trial restorations with POS.

PMID- 14653281
TI  - Marginal adaptation of indirect composites and ceramic inlay systems.
AB  - This study evaluated the marginal adaptation of four different inlay indirect
      restorative systems: feldspathic ceramic (Duceram LFC-Degussa) and three
      laboratory-processed resin composites (Solidex-Shofu; Targis-Ivoclar; Artglass
      Heraeus Kulzer). Sixty mesial-occlusal-distal (MOD) standard cavities were
      prepared in mandibular molars and divided randomly. Polyvinylsiloxane impressions
      were made and the restorations were prepared following the manufacturer's
      instructions. Marginal adaptation evaluation was accomplished using an image
      collector computer system with a digital gauging appliance at four points on the
      occlusal, proximal and gingival regions with 250x magnification. Among all the
      materials, the marginal discrepancy recorded on the gingival margins was
      statistically larger than that recorded on the proximal and occlusal regions.
      Duceram LFC showed greater marginal discrepancy than Solidex, Artglass and
      Targis, which showed no statistically significant differences among them.

PMID- 14653282
TI  - Influence of eugenol contamination on the wetting of ground and etched dentin.
AB  - Forty third molars were sectioned parallel to the occlusal surface in order to
      expose superficial and deep dentin. Exposed surfaces were ground flat with 500
      grit sandpaper. Contact angle measurements were performed to assess wettability
      using the ADSA-CD technique. Specimens were divided into two groups. Group 1 was
      the control group (no contamination). Group 2 served as the test group. Dentin
      surfaces were covered with a provisional eugenol-containing material (IRM) and
      were placed into a humidor at 37 degrees C for one week. The provisional material
      was removed. Wettability measurements of the two groups were made with water on
      ground dentin, with water and resin on etched dentin. Data were statistically
      analyzed by ANOVA, Student-Newman-Keuls multiple comparison and Student t-tests.
      Eugenol contamination did not affect the dentin wetting. Acid etching
      significantly diminished contact angle values. Dentin wetting was greater on deep
      dentin than on superficial dentin.

PMID- 14653283
TI  - The effect of organic solvents on one-bottle adhesives' bond strength to enamel
      and dentin.
AB  - This study evaluated the microtensile bond strength (pTBS) of ethanol/water- and
      acetone-based, one-bottle adhesive systems to enamel (E) and dentin (D) in the
      presence (P) or absence (A) of their respective solvents. Thirty-two freshly
      extracted third molars were flattened with 600-grit SiC paper and restored with
      Single Bond (SB) or Prime&Bond 2.1 (PB) according to the manufacturers'
      instructions and after full solvent elimination. The molars were divided into
      eight test groups (n = 4): G1-SB-E-P, G2-SB-E-A, G3-PBE-P, G4-PB-E-A, G5-SB-D-P,
      G6-SB-D-A, G7-PB-D-P and G8-PB-D-A. After applying the adhesive resins, composite
      crowns of approximately 8 mm were built up with TPH Spectrum composite. After 24
      hour water storage, the specimens were serially sectioned bucco-lingually to
      obtain 0.8 mm slabs that were trimmed to an hourglass shape, approximately 0.8
      mm2 at the bonded interface. The specimens were tested in tension using a
      universal testing machine (0.5 mm/minute). The results were statistically
      analyzed by ANOVA and Tukey test. The frequency of fracture mode was compared
      using the Kruskal-Wallis test. There were no statistically significant
      differences in mean bond strength among the groups restored with or without
      solvent for enamel. However, the results were significantly different for the
      dentin groups (MPa): G5-26.2 +/- 8.6a; G7-23.6 +/- 11.3ab; G6-12.8 +/- 2.1bc; G8
      6.2 +/- 3.1c. SEM examination indicated that the dentin group failure modes were
      significantly different from the enamel groups. The results suggest that the
      presence of organic solvents does not influence microTBS to enamel. However,
      microTBS to dentin was significantly affected by the absence of solvents in the
      adhesive system.

PMID- 14653284
TI  - The effectiveness of cure of LED and halogen curing lights at varying cavity
      depths.
AB  - This study compared the effectiveness of cure of two LED (light-emitting diodes)
      lights (Elipar FreeLight [FL], 3M-ESPE and GC e-Light [EL], GC) to conventional
      (Max [MX] (control), Dentsply-Caulk), high intensity (Elipar TriLight [TL], 3M
      ESPE) and very high intensity (Astralis 10 [AS], Ivoclar Vivadent) halogen lights
      at varying cavity depths. Ten light curing regimens were investigated. They
      include: FL1-400 mW/cm2 [40 seconds], FL2-0-400 mW/cm2 [12 seconds] --> 400
      mW/cm2 [28 seconds], EL1-750 mW/cm2 [10 pulses x 2 seconds], EL2-350 mW/cm2 [40
      seconds], EL3-600 mW/cm2 [20 seconds], EL4-0-600 mW/cm2 [20 seconds] --> 600
      mW/cm2 [20 seconds], TL1-800 mW/cm2 [40 seconds], TL2-100-800 mW/cm2 [15 seconds]
      --> 800 mW/cm2 [25 seconds], AS1-1200 mW/cm2 [10 seconds], MX-400 mW/cm2 [40
      seconds]. The effectiveness of cure of the different modes was determined by
      measuring the top and bottom surface hardness (KHN) of 2-mm, 3-mm and 4-mm thick
      composite (Z100, [3M-ESPE]) specimens using a digital microhardness tester (n =
      5, load = 500 g; dwell time = 15 seconds). Results were analyzed using
      ANOVA/Scheffe's post-hoc test and Independent Samples t-Test (p < 0.05). For all
      lights, effectiveness of cure was found to decrease with increased cavity depths.
      The mean hardness ratio for all curing lights at a depth of 2 mm was found to be
      greater than 0.80 (the accepted minimum standard). At 3 mm, all halogen lights
      produced a hardness ratio greater than 0.80 but some LED light regimens did not;
      and at a depth of 4 mm, the mean hardness ratio observed with all curing lights
      was less than 0.80. Significant differences in top and bottom KHN values were
      observed among different curing regimens for the same light and between LED and
      halogen lights. While curing with most modes of EL resulted in significantly
      lower top and bottom KHN values than the control (MX) at all depths, the standard
      mode of FL resulted in significantly higher top and bottom KHN at a depth of 3 mm
      and 4 mm. The depth of composite cure with LED LCUs was, therefore, product and
      mode dependent.

PMID- 14653285
TI  - The effect of antimicrobial pre-treatments on the performance of resin composite
      restorations.
AB  - This study evaluated the effects of four cavity pre-treatments on the
      microleakage of a fifth generation adhesive system and accompanying resin
      composite. Sixty human molars were randomly selected for cavity pre-treatment for
      the following material groups: Ultra-Etch 35% phosphoric acid gel, Ultra-Etch AB
      35% phosphoric acid gel with cetylpyridinium chloride antimicrobial agent, Ultra
      Etch 35% phosphoric acid gel followed by Concepsis chlorhexidine gluconate
      antimicrobial solution, Ultra-Etch 35% phosphoric acid gel followed by Consepsis
      Scrub chlorhexidine gluconate antimicrobial slurry and no etchant and/or cavity
      pre-treatment. Circular preparations were cut on the facial or lingual surface of
      each tooth and treated with the appropriate etchant/cavity disinfectant. PQ1 self
      priming adhesive was placed in the preparations followed by Vitalescence resin
      composite. The molars were thermocycled, sealed with nail varnish, placed in 5%
      methylene blue dye and sectioned. Leakage was assessed by dye penetration at the
      occlusal and gingival surface positions of the specimen blocks using a binocular
      microscope. The Consepsis Scrub and no pre-treatment groups revealed
      significantly greater leakage than the other groups treated with antimicrobial
      disinfectants or etchants. No significant differ. ences were shown in the two
      etchant groups that were compared, Ultra-Etch and Ultra-Etch AB. Significantly
      greater leakage was not exhibited by the same materials at the occlusal vs
      gingival surface positions.

PMID- 14653286
TI  - Influence of the polymerization process on composite resistance to chemical
      degradation by food-simulating liquids.
AB  - This study determined the influence of curing lights and modes on composite
      resistance to chemical degradation by various food-simulating liquids. Two
      different types of curing light (Halogen [H]-Elipar Trilight, 3M-ESPE; LED [L]
      Freelight, 3M-ESPE) and two curing modes (standard [S]; exponential [E) were
      evaluated in the study. Forty-five composite (Z100 [3M-ESPE]) specimens were made
      for each light-curing mode combination (HS, HE, LS and LE). The specimens were
      randomly divided into five groups of nine and exposed to the following food
      simulating liquids (FSL) for one week at 37 degrees C: distilled water, 50%
      aqueous ethanol solution, heptane and citric acid. Specimens stored in air were
      used as control. After the one week conditioning period, hardness testing was
      conducted with a digital microhardness tester (load = 500 gf; dwell time = 15
      seconds). Mean hardness (HK)/hardness deterioration (deltaHK) were subsequently
      computed and data was subjected to analysis using ANOVA/Scheffe's test (p <
      0.05). The resistance of composite to chemical degradation by FSL was
      light/curing mode dependent. Significant differences in HK and deltaHK were
      observed among the four curing techniques after conditioning in some FSL and air.
      After conditioning in water and citric acid, specimens polymerized with HE
      underwent significantly more softening compared to specimens polymerized with HS,
      LS and LE.

PMID- 14653287
TI  - Effect of surface treatment and cement maturation on the bond strength of resin
      modified glass ionomers to dentin.
AB  - This study investigated the effect of surface treatment and cement maturation on
      the bond strength of resin-modified glass ionomer cements (RMGICs) to dentin.
      Forty-two freshly extracted premolars were embedded and horizontally sectioned at
      a level 2 mm from the central fossa to obtain a flat dentin surface. The
      premolars were randomly divided into three groups of 14 teeth and treated as
      follows: Group 1 (control)--no surface treatment, Group 2--conditioned with 20%
      polyacrylic acid for 10 seconds and Group 3--etched with 37% phosphoric acid for
      15 seconds. RMGIC (Fuji II LC, GC) columns (3 mm diameter; 2 mm high) were
      applied to the dentin surface and shear bond testing was carried out after one
      week (n = 7) and one month (n = 7) storage in distilled water at 37 degrees C
      using an Instron Universal testing machine with a cross-head speed of 0.6
      mm/minute. The failure mode was examined at 40x magnification and scored with
      imaging software. The results were analyzed using ANOVA/Scheffe's post-hoc test
      and Kruskal-Wallis/Mann-Whitney test at a significance level of 0.05. The effect
      of surface treatment on shear bond strength to dentin was time dependent. Mean
      strengths ranged from 3.16 to 5.81 MPa at one week and 5.00 to 14.95 MPa at one
      month. Although no significant difference in strengths was observed among the
      groups at one week, significant differences (Group 2 > Group 1 > Group 3) were
      detected at one month. At one month, conditioned and untreated specimens
      exhibited significantly less adhesive failure than etched specimens.

PMID- 14653288
TI  - Evaluation of surface finish and polish of eight provisional restorative
      materials using acrylic bur and abrasive disk with and without pumice.
AB  - This study evaluated the effects of two finishing techniques and pumice polishing
      on the surface roughness of eight different provisional materials. Provisional
      materials included polymethylmethacrylate-based Alike, Snap, Trim and Jetand
      composite-based provisional materials Temphase, Protemp 3 Garant, Luxatemp and
      Integrity. Baseline surface roughness was measured by a profilometer, then the
      provisional materials were finished using extra fine acrylic burs or medium
      abrasive disks. The surface roughness of each sample was measured following
      finishing using a profilometer as previously stated. Each surface was then
      polished with pumice and the surface roughness was measured again. The data were
      analyzed using repeated measures of ANOVA and Bonferroni pairwise comparisons
      (alpha = 0.05). The results indicated that with composite provisional materials,
      the unfinished surfaces are smoother than with bur or abrasive-disk finished
      surfaces. Pumice application did not smooth the surface finish for all materials.
      The different types of provisional materials required different finishing
      techniques to produce the smoothest finishes.

PMID- 14653289
TI  - Effect of mouthrinses on microhardness and wear of composite and compomer
      restoratives.
AB  - This study investigated the effect of commercially available mouthrinses on the
      microhardness and wear of composite (Esthet-X, Dentsply) and compomer (Dyract
      Posterior, Dentsply) restoratives. Fifty-four hardness and 36 wear specimens of
      each material were fabricated and stored in distilled water at 37 degrees C for
      two weeks. The specimens were then randomly divided into six equal groups and
      exposed to the following solutions for 24 hours at 37 degrees C: distilled water
      [WC] (control); Listerine Original [AP] (alcohol-containing essential
      oil/phenolic compound mouthrinse); Colgate Chloropharm [AC] (alcohol-containing
      chlorhexidine mouthrinse); Oral B Tooth & Gum Care [AF] (alcohol-containing
      fluoride mouthrinse); Oral B Tooth & Gum Care Alcohol Free [OF] (alcohol free
      fluoride mouthrinse) and Oral B Sensitive [PF] (phosphoric acid containing
      fluoride mouthrinse). After conditioning, the specimens were subjected to
      hardness testing using a digital microhardness tester (load = 500 gf; dwell time
      = 15 seconds) and wear testing with a reciprocal compression-sliding system
      (contact stress = 20 MPa). Wear depth was measured every 1,000 cycles up to
      10,000 cycles using profilometry. Data was analyzed using ANOVA/Scheffe's test at
      significance level 0.05. Dyract was significantly softened by AP, while Esthet-X
      was significantly softened by AC and AP. The wear resistance of Dyract was
      significantly reduced after exposure to PF, while the wear resistance of Esthet-X
      was significantly reduced by AC. The effect of mouthrinses on hardness and wear
      was material dependent.

PMID- 14653290
TI  - Incompatibility of self-etch adhesives with chemical/dual-cured composites: two
      step vs one-step systems.
AB  - This study tested the null hypothesis that there no difference between two-step
      and one-step self-etch adhesives in their compatibility with these composites.
      The microtensile bond strengths (microTBS) of two two-step systems (Clearfil SE
      Bond, Kuraray and Tyrian SPE/One-Step Plus, BISCO) were compared with two one
      step systems (Xeno III, Dentsply DeTrey and Brush&Bond, Parkell) for their
      coupling to a dual-cured composite. Silver tracer penetration of the four
      adhesives bonded to a light-cured or a chemical-cured composite was examined
      using TEM. Significant differences in microTBSs between composite curing modes
      were seen only in the one-step adhesives. For one-step self-etch adhesives bonded
      to the chemical-cured composite, TEM revealed signs of frank composite uncoupling
      along the adhesive-composite interface, which may be attributed to the adverse
      chemical interaction between the acidic adhesive and the composite. In addition,
      "water trees" that represent channels of increased permeability with the
      polymerized adhesive layer were also observed in the one-step adhesives. Both
      features were absent along the resin-dentin interfaces when chemical-cured
      composites were coupled to the two-step self-etch adhesives.

PMID- 14653291
TI  - Variables contributing to the quality of fissure sealants used by general dental
      practitioners.
AB  - This study investigated the factors that could influence microleakage,
      penetration ability and the formation of resin tags of different sealants used in
      routine oral health care. One hundred and two caries-free extracted molars were
      divided into 34 groups of three teeth each. A questionnaire and three teeth were
      submitted to 34 dentists participating in the study. They completed the
      questionnaire anonymously based on their own clinical procedures. The teeth were
      then treated, corresponding to the questionnaires. The types of sealants were
      categorized into three groups: classical sealant, flowable composite and flowable
      compomer. The molars were thermocycled in water (5,000 cycles between 5 degrees C
      and 55 degrees C), then stained with 5% methylene blue for 24 hours. Each tooth
      was then sectioned longitudinally at three sites. Fissure type, microleakage and
      penetration ability of the sealants was evaluated with a computer-linked light
      microscope (25x magnification). Formation of resin tags at the enamel-sealant
      interfaces was examined using SEM. Variables thought to influence performance of
      the sealants were analyzed by multiple regression analyses. Classical sealants
      showed significantly lower microleakage than flowable composites and flowable
      compomers. Conventional etching with phosphoric acid was critical for sealant
      success. Agitating the etchant could improve the quality of sealing by decreasing
      microleakage significantly. In addition, the fissure types had a significant
      effect on the penetration ability of sealants.

PMID- 14653292
TI  - Initial in situ secondary caries formation: effect of various fluoride-containing
      restorative materials.
AB  - This study evaluated the effects of various restorative materials (Ariston pHc;
      Dyract; Vitremer; Tetric Ceram; Compoglass F, F2000; Hytac and Ketac Molar) on
      initial secondary caries formation in situ. Eighty-eight enamel slabs from sound
      human molars were sterilized (ethylene dioxide) and embedded in epoxy resin.
      Standardized tooth preparations were filled with the various restorative
      materials according to manufacturers' recommendations. One specimen from each
      group was inserted into one of two buccal aspects of an intraoral appliance worn
      by 11 volunteers for four weeks, day and night. Oral hygiene was performed
      without additional fluoride application. During meals and oral hygiene
      procedures, the appliances were stored in sucrose solution (10%). After in situ
      exposure, the samples were prepared for microradiographic assessment. Mineral
      content and lesion depth were evaluated by a dedicated software package (TMR
      1.24). Lesion depth and mineral loss of the carious lesions close to Ariston pHc
      was significantly lower when compared to distant parts of the same lesions (p <
      0.05; t-test, Bonferroni-Holm correction). All other materials containing
      fluoride showed no caries protective effect on surrounding enamel (p > 0.05; t
      test, Bonferroni-Holm correction). A hydroxyl-, calcium- and fluoride-containing
      restorative material hampers demineralization next to the restoration, whereas,
      fluoride release of various fluoride-containing restorative materials does not
      affect demineralization of adjacent enamel in situ.

PMID- 14653293
TI  - The effect of different types of flowable restorative resins on microleakage of
      Class V cavities.
AB  - This study evaluated the microleakage of Class V cavities restored with three
      different types of flowable resin restorative material and compared the effects
      of using their respective manufacturer's dentin adhesive or a different brand.
      Class V cavities with the occlusal margin in enamel and the gingival margin in
      dentin were prepared on the buccal and lingual surfaces of 48 non-carious human
      molars. The teeth were randomly assigned to three equal groups of 16. The first
      eight teeth in each group were restored with one of the flowable restorative
      materials (Filtek Flow, Dyract Flow, Admira Flow) using the manufacturer's
      recommended dentin adhesive (Single Bond, Prime & Bond NT, Admira Bond), and the
      remaining eight molars were restored using a different brand of dentin adhesive
      (Gluma Comfort Bond). The samples were thermocycled 200 times (5 degrees C-55
      degrees C) with a one-minute dwell time. They were then immersed in a 2% basic
      fuchsin solution for 24 hours, sectioned and analyzed by stereomicroscopy. There
      was no statistically significant difference at the occlusal margins for either
      restoration used with its respective dentin adhesive. At the gingival margins,
      there was a significant difference among all groups. Flowable ormocer (Admira
      Flow/Admira Bond) displayed the least leakage at the gingival margins. When these
      flowable restoratives were used with a different brand of dentin adhesive,
      statistically significant differences were observed both on enamel and dentin.
      None of the restoratives tested fully prevented leakage at the gingival margins.
      No significant differences in microleakage were observed among the restorative
      materials used with respect to the manufacturer's dentin adhesive or a different
      brand except for Admira Flow restorative at the gingival margins. The gingival
      margins had significantly more microleakage than the occlusal margins (p < 0.05)
      except in the Admira Flow group, where microleakage at the occlusal and gingival
      margins was almost equal.

PMID- 14653294
TI  - Effect of surface roughness of cavity preparations on the microleakage of Class V
      resin composite restorations.
AB  - This study determined whether surface roughness of the internal walls of a Class
      V resin composite preparation, using a carbide bur, a medium-grit diamond bur and
      a fine-grit diamond bur, affected the degree of microleakage of the restoration.
      The facial and lingual surfaces of 45 non-carious extracted human molars provided
      90 samples for evaluation. The specimen surfaces were assigned randomly in equal
      numbers to one of three groups (n = 30). Conservative Class V composite
      preparations were made using one of three different burs: a 330-carbide bur, a
      330 fine-grit diamond bur or a 330 medium-grit diamond bur (Brasseler USA). After
      acid etching, PQ1 (Ultradent Products Inc) primer/bonding resin and Vitalescence
      (Ultradent Products Inc) were applied and cured following the manufacturers'
      instructions. After minor finishing, the apices of all root surfaces were sealed
      with Vitrebond (3M), and the unprepared external surfaces were sealed with nail
      polish to within 1 mm of the restoration margins. The specimens were stored in
      distilled water at room temperature for 24 hours, then subjected to 1,200
      thermocycles at 5 degrees C and 55 degrees C with a 30-second dwell time. After
      cycling, the teeth were immersed in a 5% solution of methylene blue dye for 12
      hours. The molars were invested in clear acrylic casting resin, labeled, then
      sectioned once vertically approximately midway through the facial and lingual
      surfaces using a diamond coated saw blade. Microleakage was evaluated using a 10x
      microscope for the enamel and cementum surfaces and blindly scored by two
      independent examiners. In all cases, regardless of the examiner, at both the
      enamel and the dentin margins, the analysis revealed no statistically significant
      differences in microleakage across bur types. Further results show that dentin
      margins leaked significantly more than enamel margins for all bur types.

PMID- 14653295
TI  - Microhardness and color changes of human dentin with repeated intracoronal
      bleaching.
AB  - This study investigated the effects of three intracoronal bleaching techniques on
      the color and microhardness changes of human dentin and compared them to a
      control group. Twenty-four dentin slabs were derived from extracted maxillary
      anterior teeth and evenly distributed among four groups. The pulpal surface of
      each dentin slab was treated with one of the following bleaching techniques:
      thermocatalytic treatment with 30% hydrogen peroxide, walking bleaching with 2%
      sodium perborate and a combination treatment that uses both methods. In the
      control group, the specimens were treated with distilled water. All specimens
      were subjected to repeated treatment with fresh bleaching pastes on days 0, 7, 14
      and 21. During the experimental period, all specimens were placed in individual
      vials maintained at 37 degrees C and 100% humidity. CIELab color parameters and
      microhardness (VHN) were evaluated prior to the experiments and seven days after
      each treatment. All bleaching treatments effectively increased L* values and
      decreased b* values of dentin. Thermocatalytic bleaching significantly reduced
      dentin hardness to half its original value after four treatment cycles; whereas,
      treatment with either walking bleaching or the combined technique did not
      significantly affect dentin hardness. Because the combination treatment had shown
      great bleaching efficacy, it can serve as an alternative approach for severely
      stained teeth.

PMID- 14653296
TI  - A quantitative method of measuring the microleakage of thermocycled or non
      thermocycled posterior tooth restorations.
AB  - This study quantified microleakage in restorations made with three packable resin
      composites-Solitaire, SureFil and P60; one hybrid resin composite-Z250 and an
      amalgam-Dispersalloy, with or without the thermocycling process. Sixty sound,
      freshly extracted human molars were sectioned mesiodistally, creating buccal and
      lingual blocks. One hundred blocks with the flattest surface were selected.
      Cylindrical cavities with a diameter of 1.85 +/- 0.05 mm and a depth of 1.5 mm
      were prepared with a special diamond bur. The blocks were randomly assigned to 10
      test groups (n = 10): five restorative materials and two thermal stress groups
      (thermocycled groups at 3,000 cycles at 5 degrees C and 55 degrees C with a dwell
      time of one minute at each temperature, or non-thermocycled). After the
      thermocycling test, the samples were immersed in 2% methylene blue for 12 hours.
      The samples were ground and the powder prepared for analysis in an absorbance
      spectrophotometer. All the results were statistically analyzed by the Kruskal
      Wallis test and the Mann Whitney test. For the non-thermocycled groups, the means
      (microg/ml) of microleakage were: Amalgam-4.279 (a); Solitaire-4.148 (ab); Z250
      3.418 (abc); P60-3.184 (bc); SureFil-2.890 (c). For the thermocycled groups, the
      means were: Amalgam-7.572 (a); Solitaire-5.471 (a); Z250-4.330 (ab); P60-3.418
      (bc) and SureFil-2.779 (c). Thermocycling analysis showed no significant
      differences between the thermocycled and non-thermocycled groups for each
      material tested. It was concluded that no test material prevented microleakage.
      Only SureFil and P60 showed leakage means significantly lower than amalgam, with
      SureFil showing lower leakage than Solitaire. P60 only showed lower leakage than
      Solitaire in the thermocycled groups and Z250 showed results similar to the
      others materials.

PMID- 14653297
TI  - Influence of different repair procedures on bond strength of adhesive filling
      materials to etched enamel in vitro.
AB  - Contamination of etched enamel with repair bond agents during repair of dental
      restorations may interfere with the bonding of composite to enamel. This study
      examined the bond strength of adhesive filling materials to etched bovine enamel
      after pre-treatment with the repair systems Monobond S, Silibond and Co-Jet. The
      materials Tetric Ceram, Dyract and Definite and their corresponding bonding
      agents (Syntac Single Comp, Prime & Bond NT, Etch and Prime) were tested in
      combination with the repair systems. One hundred and thirty-five enamel specimens
      were etched (37% phosphoric acid, 60 seconds) and equally distributed among three
      groups (A-C). In Group A, the repair materials were applied on etched enamel
      followed by applying the composite materials without using their respective
      bonding material. In Group B, the composite materials were placed on etched
      enamel after applying the repair materials and bonding agents. In control Group
      C, the composite materials and bonding agents were applied on etched enamel
      without using the repair systems. In each sub-group, every composite material was
      applied on 15 specimens. Samples were stored in artificial saliva for 14 days and
      thermocycled 1,000 times (5 degrees C/55 degrees C). The shear bond strength of
      the samples were then determined in a universal testing machine (ISO 10477).
      Applying Monobond or Silibond followed by the use of its respective bonding
      agents resulted in a bond strength that was not statistically different from the
      controls for all filling materials (Group C). The three composites that used
      Monobond and Silibond without applying the corresponding bonding agent resulted
      in bond strengths that were significantly lower than the controls. Utilizing the
      Co-Jet-System drastically reduced the bond strength of composites on etched
      enamel. Contamination of etched enamel with the repairing bonding agents Monobond
      and Silibond does not interfere with bond strength if the application of Monobond
      and Silibond is followed by using its corresponding bonding system of the
      composites tested.

PMID- 14653298
TI  - The effect of prophylactic polishing pastes and toothbrushing on the surface
      roughness of resin composite materials in vitro.
AB  - Polishing composite restorations at recall prophylaxis may affect their surface
      roughness. This investigation evaluated the effect of prophy paste on the surface
      roughness of a microfilled (Filtek A110) and a microhybrid (Filtek Z250) resin
      composite before and after simulated toothbrushing. Twenty, two-sided samples of
      both materials were fabricated in acrylic molds against a Mylar strip (baseline).
      Three roughness readings were recorded for each surface using a Surfanalyzer 5400
      to determine the mean roughness. The samples were finished and polished with the
      Sof-Lex disk system and the surface roughness (Ra) was re-measured. Samples were
      randomly assigned and five surfaces for each material were polished with Nupro
      coarse, medium, fine or Clinpro prophy paste and the surface roughness measured
      again. All surfaces were brushed 60,000 times at 1.5Hz using a 2N brush-head
      force (Manly V-8 cross-brushing machine) in a 50:50 (w/w) slurry of toothpaste
      and water. The surface roughness was measured followed by the application of
      prophy paste as previously described and this final roughness recorded. Data were
      analyzed using repeated measures two-factor ANOVA with TUKEY HSD pairwise
      comparison as appropriate (alpha = 0.05). No significant difference in surface
      roughness was determined between the microfilled and microhybrid materials at
      baseline or disk treatment, yet significant differences were observed following
      brushing and/or prophy paste application. In conclusion, although baseline and
      disk treated surfaces were not significantly different in microfilled versus
      microhybrid composites, subsequent prophy paste application and/or simulated
      toothbrushing caused significant differences.

PMID- 14653299
TI  - Surface geometry of three packable and one hybrid composite after polishing.
AB  - This study evaluated the surface quality of four composite materials after
      polishing with six different polishing techniques. Eighty specimens were made
      using three packable composites (Definite/Degussa, SureFil/ Dentsply and
      Solitaire/Heraeus-Kulzer) and one hybrid composite (Herculite XRV/Kerr). Five
      specimens of each material were polished using flexible Sof-Lex discs. The
      remaining 75 specimens of each composite were prepared using three finishing
      protocols: a single 30 microm diamond (n = 25), two finishing diamonds (30/20
      microm; n = 25) and a 30 microm diamond followed by a tungsten carbide finishing
      bur (n = 25). Final polishing of each of the three finishing groups was
      accomplished with SuperBuff, Diafix-oral, OneGloss, Astropol and HaWe Composite
      Polishers (n = 5, each). Surface roughness was evaluated quantitatively by laser
      stylus profilometry. Average roughness (R(a)) was calculated; statistical
      analysis of the data was performed with two-way ANOVA and Scheffe post-hoc tests.
      The polished surfaces were examined qualitatively by SEM. The results showed
      significant effects on surface roughness from the different composites (p =
      0.011) and polishing systems (p < 0.001). After polishing, the Solitaire surfaces
      (R(a) = 0.72 microm) were smoother than Definite (R(a) = 0.87 microm) and SureFil
      (R(a) = 0.89 microm) and significantly smoother than Herculite (R(a) = 0.92
      microm; p = 0.011). Three of the polishing methods (SuperBuff, Diafix-oral and
      Astropol) achieved lower R(a)-values than Sof-Lex discs. The polishing quality of
      the one-step systems SuperBuff and Diafix-oral was strongly affected by the
      initial finishing protocol.

PMID- 14653300
TI  - Reversal of dentin bonding to bleached teeth.
AB  - Many studies have shown a considerable reduction in enamel bond strength of resin
      composite restorations when the bonding procedure is carried out immediately
      after bleaching. These studies claim that a certain waiting period is needed
      prior to restoration to reach the original bond strength values prior to
      bleaching. This study determined the effect of anti-oxidant applications on the
      bond strength values of resin composites to bleached dentin. Ninety human teeth
      extracted for orthodontic purposes were used in this study. The labial surface of
      each tooth was ground and flattened until dentin appeared. The polished surfaces
      were subjected to nine different treatments: 1) bleaching with gel (35% Rembrandt
      Virtuoso); 2) bleaching with gel + 10% sodium ascorbate (SA); 3) bleaching with
      gel + 10% butylhydroxyanisole (BHA); 4) bleaching with sol (35% hydrogen
      peroxide); 5) bleaching with sol + 10% sodium ascorbate; 6) bleaching with sol +
      10% BHA; 7) bleaching with gel + immersed in artificial saliva for seven days; 8)
      bleaching with sol + immersed in artificial saliva for seven days; 9) no
      treatment. After bonding application, the resin composite in standard dimensions
      was applied to all specimens. The teeth were stored in distilled water at 37
      degrees C for 24 hours and a universal testing machine determined their
      resistance to shear bond strength. The data was evaluated using ANOVA and Duncan
      tests. Bond strength in the bleached dentin group significantly decreased
      compared to the control group. On the other hand, the antioxidant treatment had a
      reversal effect on the bond strength to dentin. After the bleaching treatment,
      the 10% sodium ascorbate application was effective in reversing bond strength. In
      the samples where antioxidant was applied after the bleaching process, bonding
      strength in dentin tissue was at the same level as those teeth kept in artificial
      saliva for seven days.

PMID- 14653301
TI  - Simulated oral wear of packable composites.
AB  - Wear resistance has been a problem for the posterior application of resin
      composites. This study evaluated and compared the wear characteristics of two
      conventional and two packable composites. Opposing enamel wear was also measured.
      One traditional hybrid composite-Herculite XR (HXR), one micro-filled composite
      Heliomolar (HM) and two packable composites-Filtek P60 (P60) and Surefil (SF)
      were formed into disks (n = 10) and used as substrates for the wear test. Enamel
      was harvested from extracted human third molars and machined into cusps with a 5
      mm spherical radius (n = 40). The Oregon Health Sciences University oral wear
      simulator was used to evaluate abrasive wear and attrition of the composite
      materials and wear of the opposing enamel. The resulting enamel wear facets were
      measured and recorded in mm2 using optical scanning methods and a computer
      graphics program. Abrasion and attrition of the composite substrates were
      measured using a profilometer. Both sets of data were subjected to ANOVA and
      multiple comparison tests to determine significant differences. After wear
      testing, scanning electron micrographs were made using representative composite
      samples from each group. The packable composites showed significantly less
      attrition and abrasive wear (p < 0.001) than the conventional controls. The
      microfilled composite HM resulted in significantly lower enamel wear (p < 0.001)
      than the materials HXR and P60 but was not significantly different from the
      packable composite SF at the alpha = 0.05 level. The results of this in-vitro
      study suggest that packable composites may have improved wear resistance over
      some conventional composites. Clinical studies are needed to evaluate packable
      composites over time.

PMID- 14653302
TI  - Who should fund and control the direction of human behavior genetics? Review of
      Nuffield Council on Bioethics 2002 report, genetics and human behaviour: the
      ethical context.
AB  - In this (Nuffield Council on Bioethics 2002), the third in its series on ethics
      and related issues in genetics (see also Nuffield Council on Bioethics 1993 and
      Nuffield Council on Bioethics 1998), the Nuffield Council has focused on
      four'normal' behaviors; intelligence, personality, antisocial behavior and sexual
      orientation. This is a narrow range of behaviors and one where their discussion
      of the potential impact of predictive genetic testing is probably inappropriate.
      They also take an unduly narrow view of the purposes of behavior genetics in the
      21st century. It is not simply to estimate heritability but to understand more
      about the structure of behavior and the processes which underlie it. Their narrow
      focus and their negative approach to the history and achievements of genetics is
      reflected in their less than positive support for future behavior genetic
      research. Behavior geneticists need to do more to publicize what their field has
      achieved in order to counter the very extensive antibehavior genetics initiatives
      which are almost unique in science. At the same time, organizations such as the
      Nuffield Council need to consider carefully the impact their deliberations may
      have on research funding.

PMID- 14653303
TI  - Airbrushing heritability.

PMID- 14653304
TI  - The serotonin transporter gene-linked polymorphism and negative emotionality:
      placing single gene effects in the context of genetic background and environment.

PMID- 14653305
TI  - The utility of the non-human primate; model for studying gene by environment
      interactions in behavioral research.
AB  - Variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR)
      has been associated with anxiety and harm avoidance and is weakly associated with
      a number of neuropsychiatric disorders, including Type II alcoholism, which has a
      high rate of comorbidity with antisocial personality disorder. Studies have also
      demonstrated interactions between 5-HTLPR variation and environmental stress on
      the incidence of depression. As in humans, there is a serotonin transporter gene
      promoter length polymorphism in rhesus macaques that produces similar decreases
      in transcriptional efficiency. Macaques with histories of early-life stress have
      been shown to exhibit impulsive aggression, incompetent social behavior and
      increased behavioral and endocrine responsivity to stress. In this paper, we
      review studies performed previously in our lab and present preliminary data
      examining interactions between early rearing and serotonin transporter gene
      promoter variation on the incidences of play behavior and aggression in infant
      rhesus macaques. The data presented here highlight the importance of considering
      gene-environment interactions when studying childhood risk factors for
      aggression, anxiety and related neuropsychiatric disorders and support the use of
      the nonhuman primate for studing gene by environment interactions in behavioral
      research.

PMID- 14653306
TI  - Functional neuroimaging of genetic variation in serotonergic neurotransmission.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) is a potent modulator of the physiology and
      behavior involved in generating appropriate responses to environmental cues such
      as danger or threat. Furthermore, genetic variation in 5-HT subsystem genes can
      impact upon several dimensions of emotional behavior including neuroticism and
      psychopathology, but especially anxiety traits. Recently, functional neuroimaging
      has provided a dramatic illustration of how a promoter polymorphism in the human
      5-HT transporter (5-HTT) gene, which has been weakly related to these behaviors,
      is strongly related to the engagement of neural systems, namely the amygdala,
      subserving emotional processes. In this commentary, we discuss how functional
      neuroimaging can be used to characterize the effects of polymorphisms in 5-HT
      subsystem genes on the response of neural circuits underlying the generation and
      regulation of mood and temperament as well as susceptibility to affective
      illness. We argue that in time, such knowledge will allow us to not only
      transcend phenomenological diagnosis and represent mechanisms of disease, but
      also identify at-risk individuals and biological pathways for the development of
      new treatments.

PMID- 14653307
TI  - Experimental gene interaction studies with SERT mutant mice as models for human
      polygenic and epistatic traits and disorders.
AB  - Current evidence indicates that virtually all neuropsychiatric disorders, like
      many other common medical disorders, are genetically complex, with combined
      influences from multiple interacting genes, as well as from the environment.
      However, additive or epistatic gene interactions have proved quite difficult to
      detect and evaluate in human studies. Mouse phenotypes, including behaviors and
      drug responses, can provide relevant models for human disorders. Studies of gene
      gene interactions in mice could thus help efforts to understand the molecular
      genetic bases of complex human disorders. The serotonin transporter (SERT, 5-HTT,
      SLC6A4) provides a relevant model for studying such interactions for several
      reasons: human variants in SERT have been associated with several
      neuropsychiatric and other medical disorders and quantitative traits; SERT
      blockers are effective treatments for a number of neuropsychiatric disorders;
      there is a good initial understanding of the phenotypic features of heterozygous
      and homozygous SERT knockout mice; and there is an expanding understanding of the
      interactions between variations in SERT expression and variations in the
      expression of a number of other genes of interest for neuropsychiatry and
      neuropharmacology. This paper provides examples of experimentally-obtained
      interactions between quantitative variations in SERT gene expression and
      variations in the expression of five other mouse genes: DAT, NET, MAOA, 5-HT(1B)
      and BDNF. In humans, all six of these genes possess polymorphisms that have been
      independently investigated as candidates for neuropsychiatric and other disorders
      in a total of > 500 reports. In the experimental studies in mice reviewed here,
      gene-gene interactions resulted in either synergistic, antagonistic (including
      'rescue' or 'complementation') or more complex, quantitative alterations. These
      were identified in comparisons of the behavioral, physiological and neurochemical
      phenotypes of wildtype mice vs. mice with single allele or single gene targeted
      disruptions and mice with partial or complete disruptions of multiple genes.
      Several of the descriptive phenotypes could be best understood on the basis of
      intermediate, quantitative alterations such as brain serotonin differences. We
      discuss the ways in which these interactions could provide models for studies of
      gene-gene interactions in complex human neuropsychiatric and other disorders to
      which SERT may contribute, including developmental disorders, obesity,
      polysubstance abuse and others.

PMID- 14653308
TI  - Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the
      influence of genetic background.
AB  - Serotonin transporter (5-HTT) null mutant mice provide a model system to study
      the role genetic variation in the 5-HTT plays in the regulation of emotion.
      Anxiety-like behaviors were assessed in 5-HTT null mutants with the mutation
      placed on either a B6 congenic or a 129S6 congenic background. Replicating
      previous findings, B6 congenic 5-HTT null mutants exhibited increased anxiety
      like behavior and reduced exploratory locomotion on the light <--> dark
      exploration and elevated plus-maze tests. In contrast, 129S6 congenic 5-HTT null
      mutant mice showed no phenotypic abnormalities on either test. 5-HTT null mutants
      on the 129S6 background showed reduced 5-HT(1A) receptor binding (as measured by
      quantitative autoradiography) and reduced 5-HT(1A) receptor function (as measured
      by 8-OH-DPAT-induced hypothermia). These data confirm that the 5-HTT null
      mutation produced alterations in brain 5-HT function in mice on the 129S6
      background, thereby discounting the possibility that the absence of an abnormal
      anxiety-like phenotype in these mice was due to a suppression of the mutation by
      129 modifier genes. Anxiety-like behaviors in the light <--> dark exploration and
      elevated plus-maze tests were significantly higher in 129S6 congenic +/+ mice as
      compared to B6 congenic +/+ mice. This suggests that high baseline anxiety-like
      behavior in the 129S6 strain might have precluded detection of the anxiety-like
      effects of the 5-HTT null mutation on this background. Present findings provide
      further evidence linking genetic variation in the 5-HTT to abnormalities in mood
      and anxiety. Furthermore, these data highlight the utility of conducting
      behavioral phenotyping of mutant mice on multiple genetic backgrounds.

PMID- 14653309
TI  - Change in the iso-enzyme profiles of urinary N-acetyl-beta-D-glucosoaminidase in
      workers exposed to mercury.
AB  - The iso-enzyme profiles of urinary N-acetyl-beta-D-glucosoaminidase (NAG) were
      studied in the workers from a chloro-alkaline electrolysis plant that had been
      continuously exposed to elemental mercury. The same workers then had a work break
      of four months and were later re-exposed to mercury for another five months. The
      activities of urinary NAG in workers exposed to mercury before and after the work
      break and in the control group were 2.09 +/- 1.03 IU/L; 0.90 +/- 0.52 IU/L and
      1.13 +/- 0.35 IU/L, respectively. The fraction of the dominant A form activity in
      the total activity, in the workers exposed to mercury after a work break (85.31
      +/- 5.32%), was almost equal to the fraction of A in the control group (84.64 +/-
      2.75%). The percent fraction of A forms (A and A2) during continuous exposure was
      almost equal to the sum of the fractions A and A2 in the control group and for
      exposure after the work break. The fraction of the B form activity in the total
      activity during exposure to elemental mercury for five months after the work
      break (7.41 +/- 3.45%) was lower (P < 0.1) than the fraction of the B form in the
      control group (8.62 +/- 2.19%). The decrease in the fraction of the B form
      compared with the control group was more significant (P < 0.001) in the case of
      continuously exposed workers (5.25 +/- 2.55%). Beside the major A and B iso
      enzymes of NAG, the A2 form was also isolated, and its fraction in the control
      group (6.73 +/- 2.15%) was not negligible. For workers exposed to mercury for
      five months, it was 7.28 +/- 3.52%. It is concluded that mercury affected the
      increased exocytosis of iso-enzyme A and the inhibition of B iso-enzyme of NAG.
      The increase in activity of urinary NAG in subjects exposed to mercury was a
      consequence of the increased excretion of A form. It was established also that
      the four months work break was sufficient for the repair of renal damages that
      occurred during continuous exposure, and which were monitored by the activity of
      NAG. Thus, the effects of mercury seem to have been reversible.

PMID- 14653310
TI  - Pycnogenol in cigarette filters scavenges free radicals and reduces mutagenicity
      and toxicity of tobacco smoke in vivo.
AB  - Despite large-scale anti-smoking campaigns throughout the world, the number of
      smokers remains high and cigarette smoking continues to represent a life
      threatening health risk. Until a smoke-free society is achieved, reduction of
      cigarette smoke toxins may reduce the health burden. Current cigarette filter
      techniques are limited to the reduction of volatile tar constituents by dilution
      and by condensation on the filter surface. Vast quantities of harmful
      constituents, such as polycyclic aromatic hydrocarbons, heterocyclic (aromatic)
      amines, free radicals and reactive oxygen species, are inefficiently retained in
      the filter. We investigated whether neutralisation of free radicals in cigarette
      filters is feasible and accompanied by a reduction in smoke toxicity. Addition of
      the bioflavonoid pine bark extract Pycnogenol to cigarette filters depleted free
      radicals in a dose dependent manner. This was paralleled by a reduction of
      toxicity and mutagenicity in rodent test models. In this model system, the acute
      toxicity of cigarette smoke was markedly reduced by up to 70% in rodents with 0.4
      mg Pycnogenol in filters. Chronic exposure to cigarette smoke for 75 days
      revealed that Pycnogenol filters significantly reduced mutagenicity by up to 48%
      and decreased pathological changes in lung tissue.

PMID- 14653311
TI  - Effects of common-use pesticides on developmental and reproductive processes in
      Daphnia.
AB  - Daphnia magna were evaluated for use as a screen for pesticides that have been
      demonstrated to have estrogenic (o'p'-DDT, di-n-butyl phthalate, toxaphene), anti
      androgenic (p'p-DDE, linuron), thyroid (acetochlor, alachlor, metribuzin),
      insulin (amitraz) or lutenizing hormone (2,4-D) activity in vertebrates, and to
      establish daphnid sensitivity to these compounds. Pesticides with unknown effects
      on vertebrate endocrine systems (chlorosulfuran, cyanazine, diflubenzuron,
      metolachlor, and diquat) were also evaluated. Compounds were assayed for six days
      at environmentally relevant concentrations ranging from 0.001 to 100 mirog/L,
      using female Daphnia and their offspring. Sublethal endpoints included offspring
      sex (sex determination), clutch size (fecundity), and adult size (growth rate).
      Toxaphene was the only compound that affected sexual differentiation, increasing
      male production. Daphnia fecundity declined with exposure to toxaphene, and
      daphnid growth rates were reduced by acetochlor exposure. Diflubenzuron, o'p'
      DDT, and p'p-DDE significantly reduced Daphnia survival. No correlation existed
      between affected reproductive or developmental processes and specific endocrine
      systems or subsystems. Results from this study indicate that Daphnia make a good
      screen for assessing potential environmental impacts but are not a useful
      indicator of pesticide hormonal activity in vertebrates. This assay consistently
      detected sublethal but ecologically relevant effects of these pesticides on
      Daphnia at environmentally relevant concentrations typically below their listed
      EC50 value.

PMID- 14653312
TI  - Physicochemical determinants of linear alkylbenzene sulfonate (LAS) disposition
      in skin exposed to aqueous cutting fluid mixtures.
AB  - Linear alkylbenzene sulfonate (LAS) is added to cutting fluid formulations to
      enhance the performance of metal machining operations, but this surfactant can
      cause contact dermatitis in workers involved in these operations. The purpose of
      this study was to determine how cutting fluid additives influence dermal
      disposition of 14C-LAS in mineral oil- or polyethylene glycol 200 (PEG)-based
      mixtures when topically applied to silastic membranes and porcine skin in an in
      vitro flow-through diffusion cell system. 14C-LAS mixtures were formulated with
      three commonly used cutting fluid additives; 0 or 2% triazine (TRI), 0 or 5%
      triethanolamine (TEA), and 0 or 5% sulfurized ricinoleic acid (SRA). LAS
      absorption was limited to less than a 0.5% dose and the additives in various
      combinations influenced the physicochemical characteristics of the dosing
      mixture. LAS was more likely to partition into the stratum corneum (SC) in
      mineral oil mixtures, and LAS absorption was significantly greater in the
      complete mixture. TRI enhanced LAS transport, and the presence of SRA decreased
      LAS critical micelle concentration (CMC) which reduced LAS monomers available for
      transport. TEA increased mixture viscosity, and this may have negated the
      apparent enhancing properties of TRI in several mixtures. In summary,
      physicochemical interactions in these mixtures influenced availability of LAS for
      absorption and distribution in skin, and could ultimately influence toxicological
      responses in skin.

PMID- 14653313
TI  - Crystalline silica incubated in ascorbic acid acquires a higher cytotoxic
      potential.
AB  - Quartz incubated in an aqueous solution of ascorbic acid is partially dissolved
      and the potential to generate hydroxyl radicals from hydrogen peroxide is
      enhanced. In order to investigate whether the surface activation triggered by the
      treatment with ascorbic acid would also involve an enhancement in cell toxicity,
      a murine macrophage cell line (RAW 264.7) was exposed to untreated and ascorbic
      acid-treated quartz. Ascorbic acid pretreated quartz was more toxic than
      untreated quartz and all cells died within 24 hours after exposure. Tetrandrine
      (a Chinese drug employed to retard or reverse fibrotic lesions of silicosis in
      humans) partially reduced cell toxicity generated by ascorbic acid pretreated
      quartz.

PMID- 14653314
TI  - Flavobacterium psychrophilum infections in salmonid fish.
AB  - Flavobacterium psychrophilum is the causative agent of bacterial cold water
      disease and rainbow trout fry syndrome, disease entities responsible for
      substantial economic losses in salmonid aquaculture. Problems associated with
      epizootics include high mortality rate, increased susceptibility to other
      diseases, high labour costs of treatment and the enormous expenditure on
      chemotherapy. Despite the increasing significance of the disease, the
      pathogenesis of F. psychrophilum infections has only been partially elucidated,
      hampering the development of preventive measures to efficiently combat this
      disease condition. This literature review discusses the agent and the disease it
      causes, with emphasis on the bacterium-host interactions.

PMID- 14653315
TI  - Dynamics of experimental production of Thelohanellus hovorkai (Myxozoa:
      Myxosporea) in fish and oligochaete alternate hosts.
AB  - The dynamics of development and production of Thelohanellus hovorkai (Myxozoa)
      were examined to investigate factors inducing haemorrhagic thelohanellosis in
      carp, Cyprinus carpio L. Fresh actinospores of T. hovorkai were harvested from
      the oligochaete alternate host, Branchiura sowerbyi, and used for infection
      experiments with myxosporean-free carp. Visualization of actinospores by
      fluorescent labelling revealed that sporoplasms penetrated the gill filaments of
      carp immersed in an actinospore suspension as early as 30 min post-exposure (PE).
      Plasmodia of T. hovorkai developed in the connective tissues of various organs
      and matured 3-5 weeks PE; dispersion of myxospores from degenerate plasmodia
      occurred 5-7 weeks PE. Challenges with a high dose of actinospores (4.5 x 10(6)
      spores per fish) resulted in the onset of disease, which was more easily achieved
      by the oral intubation of actinospores than by immersion in an actinospore
      suspension. Actinosporean-free B. sowerbyi were exposed to different densities of
      myxospores (10(4)-10(6) spores per oligochaete) and subsequently reared at
      different temperatures (15, 20, 25 degrees C). At 20 and 25 degrees C,
      actinospore releases were first detected 40-43 days PE, with multiple peaks of
      release (max. 7 x 10(5) actinospores day(-1)) during the next 60 days. We
      concluded that the developmental cycle of T. hovorkai was completed within 3-5
      months at 20-25 degrees C, and that the ingestion of large numbers of
      actinospores orally, possibly by feeding on infected oligochaetes, resulted in a
      disease condition in carp.

PMID- 14653316
TI  - Genome-based detection methods of Macrobrachium rosenbergii nodavirus, a pathogen
      of the giant freshwater prawn, Macrobrachium rosenbergii dot-blot, in situ
      hybridization and RT-PCR.
AB  - The availability of specific and rapid detection methods is essential for
      monitoring the health status of farmed species, particularly in viral diseases as
      in this case early diagnosis is a critical factor in containing disease
      outbreaks. Three complementary genome-based methods were developed for the
      detection of Macrobrachium rosenbergii nodavirus (MrNV), i.e. dot-blot
      hybridization, in situ hybridization and reverse transcriptase-polymerase chain
      reaction (RT-PCR). Detection limits were established for dot-blot hybridization
      and RT-PCR and are c. 7 fg and 8 pg of viral RNA, respectively. In situ
      hybridization indicated that infection was confined to the striated muscle
      tissue. As a result of its sensitivity, RT-PCR can be used for in-depth
      investigations to examine the extent of the viral infection and establish the
      onset of infection in hatcheries. The application of RT-PCR on samples collected
      from prawn farms in China showed the possible use of this method in routine
      health monitoring.

PMID- 14653317
TI  - Reduced total hardness of fresh water enhances the efficacy of bathing as a
      treatment for amoebic gill disease in Atlantic salmon, Salmo salar L.
AB  - The current treatment for amoebic gill disease (AGD)-affected Atlantic salmon
      involves bathing sea-caged fish in fresh water, often sourced from local dams,
      for 3-4 h. In both a small-scale laboratory and an on-farm field experiment, the
      effects of water hardness on the efficacy of freshwater bathing were assessed.
      Results showed that soft fresh water (19.3-37.4 mg L(-1) CaCO3), whether it be
      naturally soft city mains water or artificially softened dam water, was more
      efficacious at alleviating AGD in affected fish than hard fresh water (173-236.3
      mg L(-1) CaCO3). Soft freshwater bathing significantly reduced viable gill
      amoebae numbers (from 73.9 to 40.9% of total count) and significantly alleviated
      gill pathology, both gross and histological. Following bathing, gross gill
      pathological scores of soft freshwater bathed fish lagged 2 weeks behind hard
      freshwater bathed fish. Significant gill lesion fragmentation, and shedding of
      lesion-associated hyperplastic tissue, was accompanied by a significant reduction
      in AGD-affected gill filaments in soft freshwater bathed fish. Furthermore, soft
      freshwater bathing alleviated the blood plasma electrolyte imbalance seen in
      control (sea water) and hard freshwater bathed fish. This study showed that the
      use of soft fresh water for bathing AGD-affected Atlantic salmon could be an
      improvement to the current method of treatment. Not only does it reduce gill
      amoeba numbers, but also, it is of a therapeutic advantage with the potential to
      reduce bathing frequency.

PMID- 14653318
TI  - Amoebic gill disease: sequential pathology in cultured Atlantic salmon, Salmo
      salar L.
AB  - Amoebic gill disease (AGD) affects the marine culture phase of Atlantic salmon,
      Salmo salar L., in Tasmania. Here, we describe histopathological observations of
      AGD from smolts, sampled weekly, following transfer to estuarine/marine sites.
      AGD was initially detected histologically at week 13 post-transfer while gross
      signs were not observed for a further week post-transfer. Significant increases
      (P < 0.001) in the proportion of affected gill filaments occurred at weeks 18 and
      19 post-transfer coinciding with the cessation of a halocline and increased water
      temperature at the cage sites. The progression of AGD histopathology, during the
      sampling period, was characterized by three phases. (1) Primary
      attachment/interaction associated with extremely localized host cellular
      alterations, juxtaposed to amoebae, including epithelial desquamation and oedema.
      (2) Innate immune response activation and initial focal hyperplasia of
      undifferentiated epithelial cells. (3) Finally, lesion expansion, squamation
      stratification of epithelia at lesion surfaces and variable recruitment of mucous
      cells to these regions. A pattern of preferential colonization of amoebae at
      lesion margins was apparent during stage 3 of disease development. Together,
      these data suggest that AGD progression was linked to retraction of the estuarine
      halocline and increases in water temperature. The host response to gill infection
      with Neoparamoeba sp. is characterized by a focal fortification strategy
      concurrent with a migration of immunoregulatory cells to lesion-affected regions.

PMID- 14653319
TI  - Outbreaks of an iridovirus disease in maricultured large yellow croaker,
      Larimichthys crocea (Richardson), in China.

PMID- 14653320
TI  - SDS-PAGE and Western blot analysis of triactinomyxon spores of Myxobolus
      cerebralis, the cause of whirling disease in salmonid fish.

PMID- 14653321
TI  - Radiation detection instruments and radiation measurement instruments.

PMID- 14653322
TI  - On the use of LiF:Mg,Ti thermoluminescence dosemeters in space--a critical
      review.
AB  - The use of LiF:Mg,Ti thermoluminescence dosemeters (TLDs) in space radiation
      fields is reviewed. It is demonstrated in the context of modified track structure
      theory and microdosimetric track structure theory that there is no unique
      correlation between the relative thermoluminescence (TL) efficiency of heavy
      charged particles, neutrons of all energies and linear energy transfer (LET).
      Many experimental measurements dating back more than two decades also demonstrate
      the multivalued, non-universal, relationship between relative TL efficiency and
      LET. It is further demonstrated that the relative intensities of the dosimetric
      peaks and especially the high-temperature structure are dependent on a large
      number of variables, some controllable, some not. It is concluded that TL
      techniques employing the concept of LET (e.g. measurement of total dose, the high
      temperature ratio (HTR) methods and other combinations of the relative TL
      efficiency of the various peaks used to estimate average Q or simulate Q-LET
      relationships) should be regarded as lacking a sound theoretical basis, highly
      prone to error and, as well, lack of reproducibility/universality due to the
      absence of a standardised experimental protocol essential to reliable
      experimental methodology.

PMID- 14653323
TI  - Dose assessment of aircraft crew in The Netherlands.
AB  - As the operator of the National Dose Registration and Information System, NRG has
      implemented a system for radiation exposure monitoring for the Dutch airlines.
      The system is based on the use of computer generated flight plans together with
      dose calculations using the CARI-6M program. Before installing the system a study
      was performed to estimate the uncertainty in the assessment of the annual dose of
      the crew members. It was concluded that the proposed system complies with
      international recommendations on the uncertainty in dose assessments in
      individual monitoring and that the operational costs of the system are low.

PMID- 14653324
TI  - The response of lif thermoluminescence dosemeters to photon beams in the energy
      range from 30 kV x rays to 60Co gamma rays.
AB  - The energy response of standard (TLD-100) and high-sensitivity (TLD-100H) LiF
      thermoluminescence dosemeters (TLDs) has been studied for photon beams with mean
      energies from about 25 keV to 1100 keV. Canadian primary standards for air kerma
      were used to establish the air kerma rates for each of the photon beams. TLDs
      were mounted in a PMMA holder and the air kerma response was measured as a
      function of energy. The EGSnrc Monte Carlo code was used to model the TLD holder
      and calculate the absorbed dose to the TLD chip per unit air kerma for each beam.
      The measured and calculated results were combined to obtain the intrinsic dose
      response of the TLD chip. Broadly, our results are consistent with existing data,
      which show a marked difference in the energy dependence of the two materials.
      However, the precision of our measurements (standard uncertainty of about 0.6%)
      has permitted the identification of features that have not been noted before. In
      particular, the energy dependence of the two materials is quite different in the
      important energy region delimited by 137Cs and 60Co gamma rays.

PMID- 14653325
TI  - Dose rate effect on micronuclei induction in cytokinesis blocked human peripheral
      blood lymphocytes.
AB  - The effect of dose rate on the induction of micronuclei (MN) in human peripheral
      blood lymphocytes was investigated over a range of dose rates from 0.125 Gy h(-1)
      to 178.2 Gy h(-1). The response of MN induction was fitted with a linear
      quadratic model and the alpha and beta coefficients were estimated. It was found
      that beta values decrease with decreasing dose rate as in the case of chromosomal
      aberration. At the dose rate of 0.125 Gy h(-1), pure linear response of MN
      induction was observed. An attempt was made to simulate the calibration curve for
      the purpose of biological dosimetry at different dose rates and exposure times.
      The yields when simulated with the exposure time or the dose rate are in
      agreement with experimental results.

PMID- 14653326
TI  - Human biokinetics of inhaled terbium oxide.
AB  - Four healthy men inhaled a monodisperse aerosol of 160Tb-labelled terbium oxide
      particles. The behaviour of the tracer was studied through measurements of body
      radioactivity and of its urinary and faecal excretion. Estimated early faecal
      losses in the four subjects ranged from 3% to 31% of the initial respiratory
      tract deposit; most of the residue had become systemic within a year, with the
      principal deposit apparently in bone. Interference from this systemic deposit
      prevented accurate determination of the long-term pulmonary clearance kinetics,
      but the pattern was broadly what would be expected for Type M materials in the
      ICRP's Human Respiratory Tract Model. Averaged trends in the whole-body residue
      after approximately 1 year suggest a clearance half-life of approximately to 5 y.

PMID- 14653327
TI  - Doses to fetal and maternal organs from intravenous 59FeCl3 or 57CoCl2.
AB  - Doses from intravenous intakes of 59Fe or 57Co chloride during pregnancy were
      estimated. Near term fetal organ doses were derived via the MIRDOSE3 newborn
      phantom, with mean dose/cumulated activity (S) values rescaled for compatibility
      with near term fetus whole body S. A detailed in vivo biodistribution database
      provided indications of residence times in important maternal and fetal organs.
      59Fe doses to the fetus whole body from early to late pregnancy were 7-11 mGy
      MBq(-1) (8.5-14.3 mSv MBq(-1)), similar to that to the mother. Doses to near term
      fetal spleen (59 mGy MBq(-1)), liver (36), and red marrow (9) were similar or
      higher than to the mother. 57Co doses to fetus whole body from early to late
      pregnancy were 0.7-3.3 mGy MBq(-1) (2.5-8.2 mSv MBq(-1)), similar or higher than
      to the mother. Doses to near term fetal small intestine (34 mGy MBq(-1)). liver
      (4.7) and red marrow (2.7) were similar or higher than to the mother.

PMID- 14653328
TI  - Characteristics of radon and its progeny concentrations in air-conditioned office
      buildings in Tokyo.
AB  - A series of measurements were carried out to understand the characteristics of
      radon and its progeny in air-conditioned office buildings. Long-term measurements
      of radon were made with etched track detectors. Continuous measurements of radon
      and its progeny concentrations were also conducted in some buildings to study
      their temporal variations. The results show that radon and its progeny
      concentrations routinely varied along with the working activities. They are
      generally low while people are working, due to air conditioning, whereas they
      rise steadily after the air conditioning stops. When considering action levels
      not only in homes but also workplaces, attention should be paid to annual doses
      from the viewpoint of radiation protection. The annual dose is generally
      estimated with a long-term measurement of radon concentration using a passive
      device such as an etched track detector. Since its reading corresponds to a long
      term average concentration regardless of working hours, but, the annual dose will
      be overestimated. When comparing a real dose after considering the working hours,
      they differ by a factor of more than 2.

PMID- 14653329
TI  - Decommissioning of a 60Co unit and estimation of personal doses.
AB  - Chang-hua Christian Hospital needs to uninstall the 60Co unit. The mode of this
      60Co teletherapy unit is SHIMADZU RTGS-10. The original lead head was taken as
      the source container of this 60Co unit. The source head was dismantled and put
      into the prepared wooden box, after the source was sealed. This study describes
      the planning and dismantling of the retirement and transport of the 60Co unit,
      and personal doses measured during the procedure. This work estimates the doses
      of radiation received by exposed workers during the dismantling of the machine.
      The workers received doses of approximately 53 microSv. This study shows that the
      original lead head can be used as the source container of this 60Co unit. The
      60Co machine was smoothly dismantled and transported by conscientious and careful
      workers, using planned and controlled radiation protection, following the ALARA
      (as low as reasonably achievable) rule.

PMID- 14653330
TI  - Half a century of internal dosimetry.

PMID- 14653331
TI  - Reliability of the ICRP's dose coefficients for members of the public. III.
      Plutonium as a case study of uncertainties in the systemic biokinetics of
      radionuclides.
AB  - This paper is a case study of the validity of different data sources and
      modelling approaches commonly used to build biokinetic models for radionuclides.
      The paper examines the basis and apparent predictive accuracy of each of the
      biokinetic models for Pu used over the years by the International Commission on
      Radiological Protection (ICRP), in view of recent improvements in the database.
      The results of this study and similar retrospective studies for other elements
      suggest the following five points. (1) Extrapolation of biokinetic data from
      laboratory animals to man is particularly uncertain for the liver due to
      qualitative differences among species in the handling of many elements by this
      organ. (2) As a 'default' approach to biokinetic modelling or model assessment,
      biokinetic data for unhealthy human subjects should be given higher weight than
      information extrapolated across animal species or chemical families, but there
      are counter-examples. (3) Little confidence can be placed in biokinetic model
      predictions for long times after exposure based solely on curve fits to short
      term biokinetic data. (4) Bioassay and dosimetry models for a radionuclide should
      not be developed separately. (5) Where feasible, the systemic biokinetic model
      for a radionuclide should be developed within a physiologically realistic model
      structure, because this allows biokinetic data from experimental studies to be
      supplemented with physiological information, provides a basis for extrapolation
      of data across animals species or chemical families, results in models that can
      be used for both bioassay interpretation and dosimetry, and provides a logical
      basis for extrapolation of data to subgroups of the population (e.g., various
      ages) or to times outside the period of observation.

PMID- 14653332
TI  - On the determination of the post-irradiation time from the glow curve of TLD-100.
AB  - The ratio of peak 3 to the sum of peaks 4 + 5 in TLD-100 was measured for various
      pre-irradiation and post-irradiation time periods, under conditions
      characteristic of routine personal dosimetry. It was confirmed that the value of
      this ratio depends only on the elapsed time between the prior readout and the
      present one, independent of the moment when the irradiation took place during the
      total time interval (storage time). This effect indicates that fading of peak 3
      seems to be due mainly to changes in the unoccupied traps, and not to decay of
      trapped charges, being almost independent of the presence of electrons or holes
      in the traps. This observation leads to the conclusion that the suggestions in
      the past to use the decay of peak 3 in TLD-100 for the measurement of the elapsed
      time between irradiation and readout may have been wrong. On the other hand, the
      decay of peak 2 can be used to measure the elapsed time from irradiation, since
      the rate of decay is different when related to pre-irradiation and post
      irradiation times, indicating a much higher decay rate of the trapped charges
      (Randall-Wilkins decay). However, because of the fast decay rate of peak 2, its
      use for determination of the elapsed time since irradiation is of little
      practical significance.

PMID- 14653333
TI  - Induction of chromosome aberration in human lymphocytes and its dependence on X
      ray energy.
AB  - The variations of dose response with X ray energy observed with the human
      lymphocyte dicentric assay is examined. In order to determine reliably the
      initial slopes (RBEm) many cells need to be analysed at low doses. Insufficient
      analysis may explain some reported interlaboratory differences in fitted dose
      response coefficients. One such discrepancy at 150 kVp, E = 70 keV is examined.
      Data are also presented for an X ray spectrum of 80 kVp, E = 58 keV. Over the
      photon energy range 20 keV X rays to 1.25 MeV gamma rays RBEm varies by about a
      factor of 5, with the lower energies being more effective. This is consistent
      with microdosimetric theory. By contrast, in radiological protection a radiation
      weighting factor of 1.0 is assumed for all photons when assessing the risk of
      inducing cancer at low doses. The measured variations of biological effect with
      photon energy have led to suggestions that the lower energies, as used for some
      diagnostic radiology, carry a greater risk per unit dose than is normally assumed
      by those involved in radiological protection. Interpretation of the data reported
      in this paper does not support this view.

PMID- 14653334
TI  - Conversion coefficients from fluence to effective dose for heavy ions with
      energies up to 3 GeV/A.
AB  - Radiological protection against high-energy heavy ions has been an essential
      issue in the planning of long-term space missions. The fluence to effective dose
      conversion coefficients have been calculated for heavy ions using the particle
      and heavy ion transport code system PHITS coupled with an anthropomorphic phantom
      of the MIRD5 type. The calculations were performed for incidences of protons and
      typical space heavy ions--deuterons, tritons, 3He, alpha particles, 12C, 20Ne,
      40Ar, 40Ca and 56Fe--with energies up to 3 GeV/A in the isotropic and anterior
      posterior irradiation geometries. A simple fitting formula that can predict the
      effective dose from almost all kinds of space heavy ions below 3 GeV/A within an
      accuracy of 30% is deduced from the results.

PMID- 14653335
TI  - Analysis of dose-LET distribution in the human body irradiated by high energy
      hadrons.
AB  - For the purposes of radiological protection, it is important to analyse profiles
      of the particle field inside a human body irradiated by high energy hadrons,
      since they can produce a variety of secondary particles which play an important
      role in the energy deposition process, and characterise their radiation
      qualities. Therefore Monte Carlo calculations were performed to evaluate dose
      distributions in terms of the linear energy transfer of ionising particles (dose
      LET distribution) using a newly developed particle transport code (Particle and
      Heavy Ion Transport code System, PHITS) for incidences of neutrons, protons and
      pions with energies from 100 MeV to 200 GeV. Based on these calculations, it was
      found that more than 80% and 90% of the total deposition energies are attributed
      to ionisation by particles with LET below 10 keV microm(-1) for the irradiations
      of neutrons and the charged particles, respectively.

PMID- 14653336
TI  - Early detection of radioactive fallout by gamma spectrometry.
AB  - Radioactive fallout should be detected as early as possible. A new and efficient
      method for detection of low-level irradiation from manmade radioactivity is
      developed. Radiation abnormalities are detectable down to air kerma rates of 0.5
      to 1.0 nGy h(-1) for 137Cs and even lower for 131I. For multi-gamma energy
      radioactivity the detection level is 2.6-3.5 nGy h(-1). A standard NaI detector
      and a 512-channel analyser are used together with noise adjusted singular value
      decomposition (NASVD). Statistical noise is removed and the measured spectra are
      reproduced using spectral components produced by NASVD. Stripping is not used and
      false alarms due to washout of atmospheric radon progeny are almost eliminated.
      Detection levels and the criteria for setting warning and alarm levels are
      discussed. The method may also be useful in other situations, for example where
      low-level signals from radioactive sources need to be detected.

PMID- 14653337
TI  - Conversion factors for a mobile survey method by car in the Chernobyl area.
AB  - Conversion factors for the purpose of mobile survey by car in the Chernobyl area
      have been evaluated using simulation calculations. In the calculations, the width
      of road is assumed as being 4 m, 10 m and 20 m and the surrounding area is
      divided into ten zones contaminated homogeneously by 137Cs with different depth
      profiles in the ground. The air kerma contribution from all zones to the road is
      simulated. A conversion factor is calculated by dividing the air kerma rate in
      typical land-use adjacent to the road by that on the road. Conversion factors in
      various land uses around the roads are examined. The calculated conversion
      factors agree with the conversion factors measured in the Chernobyl area within
      an accuracy of 20%. Further, basic data, needed for composing conversion factors
      appropriate to other contaminated regions with different depth distributions from
      the Chernobyl area, are also indicated.

PMID- 14653338
TI  - Distribution of equivalent doses to skin of the hands of nuclear medicine
      personnel.
AB  - During direct contact with radiation sources, for example in nuclear medicine
      departments, the skin of the hands of workers is the area most exposed to
      radiation. Measurements with finger dosemeters containing thermoluminescent
      detectors showed that doses received may reach values as high as 100 mSv y(-1).
      The specific nature of work performed with isotopes contributes to the
      considerable differences in the value of an equivalent dose received by the
      metacarpus, wrist and fingertips. The annual equivalent doses to which fingertips
      are exposed may exceed the annual dose limit of 500 mSv.

PMID- 14653339
TI  - Providing a complete service to clients: a key message for final-year students.

PMID- 14653340
TI  - Use of mycobacterial peptides and recombinant proteins for the diagnosis of
      bovine tuberculosis in skin test-positive cattle.
AB  - More accurate tests are required to test cattle which have reacted positively in
      the tuberculin skin test. For this purpose, a range of mycobacterial antigens,
      MPB59, MPB64, MPB70, MPB83, ESAT-6 and CFP10, were used either as recombinant
      proteins or as synthetic peptides in the whole blood interferon-gamma (IFN-gamma)
      test. Groups of uninfected cattle with typical 'non-specificity' problems were
      targeted, in particular animals with skin tuberculosis, animals vaccinated
      against Johne's disease and animals that were positive in the standard purified
      protein derivative (PPD)-based IFN-gamma test. The two study groups consisted of
      74 Mycobacterium bovis-culture positive animals and 72 uninfected animals, all of
      which tested positive in the caudal fold tuberculin skin test eight to 28 days
      before the blood test. The use of combinations of ESAT-6 and CFP10 antigens,
      either as recombinant proteins or peptides, detected similar percentages of M
      bovis-infected animals as the PPD-based IFN-gamma test, but produced
      significantly fewer false positive reactions. The PPD-based IFN-gamma test was
      very effective in differentiating animals vaccinated against Johne's disease that
      were skin-test positive from those with bovine tuberculosis, and the use of PPD
      or specific mycobacterial antigens minimised the number of false positive
      reactions in animals with skin tuberculosis.

PMID- 14653341
TI  - Specificity of three ELISA-gE kits for screening pig meat for antibodies to
      Aujeszky's disease.
AB  - Muscle samples (20 g) from 2025 pig carcases from Aujeszky's disease-free
      holdings were collected at the slaughterhouse. The samples were frozen and thawed
      to obtain meat juice, which was then analysed by three ELISA-gE test kits in
      parallel, to assess their specificity. After two cycles of freezing and thawing,
      2.2 per cent of the samples were dry. Three times more of the samples from the
      sow carcases than from the finisher carcases yielded insufficient juice (< 220
      microl). To validate the results of the specificity study, the sensitivity of the
      test kits was evaluated on 45 samples from gE-seropositive sows. On the basis of
      the results from 1879 samples, the specificity of the ELISA-gE kits was between
      0.995 and 1.000, depending on the classification of the doubtful results. In the
      case of a positive or doubtful result, it proved useful to repeat the test on the
      same sample, in order to limit the number of false positive results.

PMID- 14653342
TI  - Juvenile laryngeal paralysis in three Siberian husky x Alaskan malamute puppies.
AB  - Three three-month-old Siberian husky x Alaskan malamute crossbreds had suffered
      episodic inspiratory dyspnoea and stridor for four to eight weeks and their
      endurance had decreased. In two of them bilateral, and in the other unilateral,
      laryngeal paralysis was diagnosed by laryngoscopy. In the nucleus ambiguus of the
      dogs there was a depletion of motor neurons, neuronal degeneration and mild
      gliosis, but there were no lesions in the root and peripheral segments of the
      recurrent laryngeal nerves.

PMID- 14653343
TI  - Induction of anaesthesia in pigs using a new alphaxalone formulation.

PMID- 14653344
TI  - Identification of Cryptosporidium parvum 'cattle' genotype from a severe outbreak
      of neonatal foal diarrhoea.

PMID- 14653345
TI  - Outbreak of tick paralysis in a nomadic sheep flock in Iran.

PMID- 14653346
TI  - Detection of leptospiral antibodies in caimans from the Argentinian Chaco.

PMID- 14653347
TI  - SPVS seminar for final-year students.

PMID- 14653348
TI  - Gangrenous mastitis in a dairy herd.

PMID- 14653349
TI  - Laboratory animal medicine.

PMID- 14653350
TI  - Anthelmintic resistance and use of anthelmintics in horses.

PMID- 14653351
TI  - Analysis of a Bayesian repeated measures model for detecting differences in GP
      prescribing habits.
AB  - A linear mixed model is used to detect a change, if any, in the prescribing
      habits in the UK at the general practice (family medicine) level due to an
      educational intervention given repeated measures data before and after the
      intervention and a control group. Inferences are corrected for general practice
      size and fundholding status. The estimates of the model parameters are obtained
      using Bayesian inference by applying Gibbs sampling. We develop three different
      priors for the parameters of the model. These three priors correspond to
      'sceptical,' 'reference' and 'enthusiastic' priors in terms of the opinion about
      the treatment effects that they represent. We compare the results obtained by
      using these three priors for the parameters in the random effects model.

PMID- 14653352
TI  - Bayesian techniques for sample size determination in clinical trials: a short
      review.
AB  - The aim of this paper is to review some key techniques of Bayesian methods of
      sample size determination. The approach is to cover a small number of simple
      problems, such as estimating the mean of a normal distribution. The methods
      considered are in two groups: inferential and decision theoretic. In the
      inferential Bayesian methods of sample size determination, we are solely
      concerned with the inference about the parameter(s) of interest. The fully
      Bayesian or decision theoretic approach treats the problem as a decision problem
      and employs a loss or utility function.

PMID- 14653353
TI  - Are our data symmetric?
AB  - Skewness indicates a lack of symmetry in a distribution. Knowing the symmetry of
      the underlying data is essential for parametric analysis, fitting distributions
      or doing transformations to the data. The coefficient of skewness is the commonly
      used measure to identify a lack of symmetry in the underlying data, although
      graphical procedures can also be effective. We discuss three different methods to
      assess skewness: traditional coefficient of skewness index, skewness index based
      on the L-moments discussed by Hosking and the asymptotic test of symmetry
      developed by Randles et al. With this work, we provide easy-to-implement S-PLUS
      functions as well as discuss the advantages and shortcomings of each technique.

PMID- 14653354
TI  - Meta-analyses involving cluster randomization trials: a review of published
      literature in health care.
AB  - Throughout the 1980s and 1990s cluster randomization trials have been
      increasingly used to evaluate effectiveness of health care intervention. Such
      trials have raised several methodologic challenges in analysis. Meta-analyses
      involving cluster randomization trials are becoming common in the area of health
      care intervention. However, as yet there has been no empirical evidence of
      current practice in the meta-analyses. Thus a review was performed to identify
      and examine synthesis approaches of meta-analyses involving cluster randomization
      trials in the published literature. Electronic databases were searched for meta
      analyses involving cluster randomization trials from the earliest date available
      to 2000. Once a meta-analysis was identified, papers on the relevant cluster
      randomization trials included were also requested. Each of the original papers of
      cluster randomization trials included was examined for its randomized design and
      unit, and adjustment for clustering effect in analysis. Each of the selected meta
      analyses was then evaluated as to its synthesis concerning clustering effect. In
      total, 25 eligible meta-analyses were reviewed. Of these, 15 meta-analyses
      reported simple conventional methods of the fixed-effect model as method of
      analysis, while six did not incorporate the cluster randomization trial results
      in the synthesis methods but described the trial results individually. Three meta
      analyses attempted to account for the clustering effect in the synthesis methods
      but approaches were in arbitrary. Fifteen meta-analyses included more than one
      cluster randomization trial, each of which included cluster randomization trials
      with a mixture of randomized designs and units, and units of analysis. These
      mixture situations might increase heterogeneity, but have not been considered in
      any meta-analysis. Some methods dealing with a binary outcome for some specific
      situations have been discussed. In conclusion, some difficulties in the
      quantitative synthesis procedures were found in the meta-analyses involving
      cluster randomization trials. Recommendations in the applications of approaches
      to some specific situations in a binary outcome variable have also been provided.
      There are still, however, several methodologic issues of the meta-analyses
      involving cluster randomization trials that need to be investigated further.

PMID- 14653355
TI  - Comparison of methods to identify outliers observed in health services small area
      variation studies.
AB  - Small area variation analysis (SAV) is an established methodology in health
      services and epidemiological research. The goal is to demonstrate that rates
      differ across areas, and to explain these differences by differences in physician
      practice styles or patient characteristics. While the SAV statistics provide an
      overall variation estimate, they do not provide a statistical means to identify
      significant outliers. We compared the chi-square (chi2) test with three
      approaches in determining significant outliers in SAV. We used data from the
      Canadian Institute for Health Information (CIHI) for Ontario residents discharged
      between 1989 and 1991. Coronary artery bypass surgery, hysterectomy and hip
      replacement data were used to compare four statistics in determining outliers:
      the chi2 test, Swift's approximate bootstrap confidence interval (ABC),
      Carriere's T2 (T2) with simultaneous confidence intervals (SCI), and Gentleman's
      normalized scores (GNS). Both the ABC and SCI correct the skewness of the
      distribution of the adjusted rates. With large data, confidence intervals
      calculated by the normal or the ABC methods are indistinguishable. The T2 can be
      applied to also nonbinary events. For binary events, it is asymptotically the
      same as the chi2. The GNS ranks the rates, but the distribution of these ranks
      does not differ significantly from that of the adjusted rates. We concluded that
      when using large data with binary events, there is little advantage in using the
      ABC, SCI or GNS over the commonly known chi2. The chi2 remains a useful tool in
      small area variation analysis to 'screen' or flag potential differences beyond
      chance alone.

PMID- 14653356
TI  - The emerging role of gene therapy in the treatment of cardiovascular diseases.
AB  - Cardiovascular disease is the number one source of morbidity and mortality in the
      United States. Therapies directed at a variety of cardiovascular diseases have
      blossomed over the last several decades. The advent of gene therapy, first as an
      intriguing tool, and subsequently with the early successes of gene trials
      involving the treatment of SCID, led to the development of gene therapy as a
      potentially exciting and viable therapy in cardiovascular diseases. A variety of
      novel vector technologies and delivery systems have been developed to more
      efficiently deliver the gene product to the desired organ or tissue bed. Early
      clinical trials focused on stimulating angiogenesis. Subsequently, a number of
      other aspects of cardiovascular disease have been identified as potential targets
      for gene therapy, including the prevention of restenosis, the prevention and
      treatment of thrombosis, and the prevention of transplant vasculopathy. With over
      forty clinical human trials either completed or currently enrolling,
      cardiovascular gene therapy has proven to be safe and initial results suggest its
      efficacy.

PMID- 14653357
TI  - Basic and clinical aspects of copper.
AB  - An oxygen-rich atmosphere obligated living organisms to cope with reactive oxygen
      species (O2-, H2O2, OH*) that were the unavoidable by-products of cellular
      metabolism. As a redox cofactor Cu was selected as a co-catalyst for numerous
      biological processes, many involving the utilization of oxygen. Inadequate or
      excessive intake of Cu can be pathogenic and life-threatening. Mutations to genes
      that code for Cu-transporting ATPase enzymes are the molecular basis of Wilson
      and Menkes diseases and more recently Cu has been identified as a preemptory
      factor in amyloid and prion diseases. This review is dedicated to bringing
      historical and timely information on Cu transport, metabolism and homeostasis to
      the attention of those not familiar with this important mineral. Other
      comprehensive reviews are available to the interested readers.

PMID- 14653358
TI  - Regeneration of the vocal fold using autologous mesenchymal stem cells.
AB  - The aim of this study was to regenerate the injured vocal fold by means of
      selective cultured autologous mesenchymal stem cells (MSCs). Eight adult beagle
      dogs were used for this experiment. Selective incubation of MSCs from bone marrow
      was done. These MSCs were submitted to 3-dimensional incubation in 1%
      hydrochloric acid atelocollagen. Three-dimensional incubated MSCs were injected
      into the left vocal fold, and atelocollagen only was injected into the right
      vocal fold of the same dog as a control. Four days after injection, the posterior
      parts of the vocal folds were incised. The regeneration of the vocal fold was
      estimated by morphological and histologic evaluations. Our results showed that 3
      dimensional incubated MSCs were useful in the regeneration of the injured vocal
      fold. This study shows that damaged tissues such as an injured vocal fold would
      be able to be regenerated by tissue engineering.

PMID- 14653359
TI  - Dysphagia, hoarseness, and unilateral true vocal fold motion impairment following
      anterior cervical diskectomy and fusion.
AB  - The charts of 100 patients who underwent anterior cervical diskectomy with fusion
      performed at our institution between January 1996 and February 1999 were
      reviewed. The incidences of hoarseness, dysphagia, and unilateral true vocal fold
      motion impairment were calculated. Univariate logistic regression was used to
      estimate the relationship of several patient and technical factors to the rates
      of occurrence of hoarseness and dysphagia. Patient age was found to be a
      significant predictor of postoperative dysphagia (p < .006), with an odds ratio
      of 1.113 (95% confidence limits, 1.04, 1.21) per year of age. Other factors
      studied were not found to be significant predictors. The overall incidence of
      these complications from the world literature was also calculated. The overall
      incidences of dysphagia, hoarseness, and unilateral true vocal fold motion
      impairment in the literature were calculated as 12.3%, 4.9%, and 1.4%,
      respectively. We conclude that dysphagia, hoarseness, and unilateral vocal fold
      motion impairment continue to remain significant complications of anterior
      cervical diskectomy with fusion. Older patients may be at higher risk for
      dysphagia.

PMID- 14653360
TI  - Cymetra injection for unilateral vocal fold paralysis.
AB  - Cymetra has shown excellent tissue biocompatibility, a low rate of resorption,
      and no tissue reactivity when injected for treatment of facial wrinkling. On the
      basis of these findings, we hypothesize that injection of Cymetra into the
      thyroarytenoid muscle for treatment of glottal incompetence may demonstrate
      similar findings and lead to long-term improvement in voice quality and glottal
      gap closure. Ten patients with breathy dysphonia caused by unilateral vocal fold
      paralysis underwent transoral injection of Cymetra into the thyroarytenoid
      muscle. Each subject underwent preoperative and postoperative acoustic analysis,
      aerodynamic measures, taped voice sampling, and videostroboscopy. Significant
      improvements were identified in maximum phonation time, relative glottal area,
      and subjective judgment of glottal competency. These results were not maintained
      at the 3-month study interval. No significant change in quantitative or
      subjective voice quality was noted for the study group during the investigation.
      Resorption of Cymetra may play a significant role in contributing to these
      findings.

PMID- 14653362
TI  - Neck dissection shoulder syndrome: quantification and three-dimensional
      evaluation with an optoelectronic tracking system.
AB  - Objective 3-dimensional biomechanical changes of the shoulder at rest or during
      arm elevation were measured by means of a new specific method using an
      optoelectronic detection system that was developed for computer-aided surgery.
      Additionally, the shoulder syndrome following neck dissection was evaluated by
      the recognized orthopedic shoulder Constant score. The statistical evaluation
      encompassed 12 patients with unilateral radical neck dissection (RND), 12
      patients with unilateral modified radical neck dissection (MRND) with
      preservation of the accessory nerve, and 10 healthy subjects. The healthy
      shoulders showed normal kinematic behavior, the so-called "scapulohumeral rhythm"
      (SHR). After MRND, the static scapular position and SHR showed no significant 3
      dimensional variations. In contrast, RND produced a highly significant scapular
      displacement at rest (p < .01) and a near-total abolition of SHR. The Constant
      scores were significantly lower after RND than after MRND (p < .01). Three
      dimensional evaluation of the shoulder syndrome supports the Constant score,
      quantifying what can be measured objectively.

PMID- 14653361
TI  - Tuberculous otitis media: clinical aspects of 12 cases.
AB  - The clinical features of tuberculous otitis media (TOM) have changed. This study
      was performed to evaluate changing trends in the clinical manifestations of TOM.
      We reviewed a series of 12 cases of TOM (13 ears) recently treated at Osaka
      Prefectural Habikino Hospital. The results showed a mean age of 41 years and a
      male predominance of 1.4 to 1. Central or total perforations of the tympanic
      membrane were observed in most cases, but none of the patients had multiple
      perforations. Nine patients (75%) had active pulmonary tuberculosis. Normal lung
      status or inactive pulmonary tuberculosis was significantly more frequent in the
      older age group. Diagnosis of primary TOM required more time than that of
      secondary TOM. Most cases of primary TOM had high infectiousness of the primary
      lesion. We summarize the clinical features of patients who should be evaluated
      for TOM.

PMID- 14653363
TI  - Efferent system degeneration in the human temporal bone.
AB  - Sense organ deposits have been described in temporal bones from patients with
      vestibular neuronitis, Meniere's disease, and benign paroxysmal positional
      vertigo that are not found in a comparable series of temporal bones without
      vestibulopathy. Because the recurrent vestibulopathies are caused by vestibular
      ganglionitis and the vestibulocochlear anastomosis was degenerated in these
      temporal bones, the deposits may represent the end buds of regenerating efferent
      axons injured in passage through the vestibular ganglion. Such neural buds have
      been described with transmission electron microscopy in animals after vestibular
      nerve transection and in a human temporal bone with endolymphatic hydrops. The
      buds may be visible by light microscopy, because their size is comparable to that
      of hair cell nuclei and they stain blue with hematoxylin because of their nucleic
      acid content. The variable location and size of these deposits (buds) in the
      labyrinthine sense organs is described to aid in the recognition of efferent
      system injury in human temporal bones.

PMID- 14653364
TI  - Leukotriene receptor antagonist pranlukast suppresses eosinophil infiltration and
      cytokine production in human nasal mucosa of perennial allergic rhinitis.
AB  - The purpose of this study was to investigate the influence of pranlukast on
      eosinophilic inflammation and cytokine production in human nasal mucosa. Twelve
      patients were treated with pranlukast, and samples were obtained from the nasal
      mucosa of the inferior turbinate. With respect to cell infiltration, a
      significant decrease was observed in the percentage of inflammatory cells
      (secreted eosinophil cationic protein [EG2] and neutrophil elastase) after
      treatment. The levels of cytokines and chemical mediators (interleukin [IL]-4, IL
      5, RANTES [regulated on activation, normal T cell expressed and secreted],
      cysteinyl leukotrienes, IL-1beta, tumor necrosis factor-alpha, and IL-8) assessed
      by enzyme-linked immunosorbent assay and enzyme immunoassay were significantly
      decreased. These results indicate that pranlukast decreased the levels of a
      majority of the cytokines in nasal mucosa, leading to improvement in subjective
      nasal symptoms. Furthermore, these results support the hypothesis that pranlukast
      exerts its therapeutic action primarily by blocking the leukotriene receptors on
      eosinophils.

PMID- 14653365
TI  - Endolaryngeal extrusion of expanded polytetrafluoroethylene implant after
      medialization thyroplasty.
AB  - Various nonresorbable implants are currently used worldwide for medialization
      thyroplasty in patients with unilateral vocal cord paralysis. The Gore-Tex
      (expanded polytetrafluoroethylene) implant was introduced in the late 1990s. At
      our institution, 27 patients with unilateral laryngeal nerve paralysis had
      medialization thyroplasty with a Gore-Tex implant during the years 1998 to 2002.
      The current report documents our first case of endolaryngeal extrusion of a Gore
      Tex implant.

PMID- 14653366
TI  - Stroboscopic observation of vocal fold vibration with the videoendoscope.
AB  - Asahi Optical Co, Ltd (Tokyo, Japan), has manufactured a trial thin
      videoendoscope with an instantaneous RGB (red-green-blue) system. We have
      developed a new laryngostroboscopic system using this videoendoscope. In this
      article, we report the performance of the clinical trial of this new and useful
      videoendoscopic system for stroboscopy, and compare it to conventional
      stroboscopy using a flexible fiberscope or rigid endoscope. This new thin
      videoendoscope has the following characteristics. A small charge-coupled device
      (CCD) chip is built into the tip of this endoscope, and an instantaneous RGB
      system is used. The outer diameters of its tip (4.1 mm) and the insertion tube
      (3.7 mm) of the videoendoscope are relatively small. The videoendoscope system is
      compact. Stroboscopic observation was conducted with this videoendoscope in
      conjunction with a laryngostroboscope. Compared to stroboscopy with a
      conventional flexible fiberscope or rigid endoscope, this stroboscopic system has
      several clear advantages. It presents clear dynamic color images on a color video
      monitor and provides excellent resolution and recording, thus yielding high
      diagnostic accuracy. The diameter of the videoendoscope is relatively small and
      results in less discomfort for patients, even for children. The videoendoscope
      allowed the doctors to perform pernasal endoscopy. Therefore, there is less
      limitation in the range of subjects for examination. Patients are able to phonate
      holding a normal head position, and are thereby able to produce varying vocal
      sounds in the habitual or normal manner during examination. The new stroboscopy
      system using a videoendoscope is a very useful examination tool that has the
      advantages of both a conventional flexible fiberscope and a rigid endoscope.

PMID- 14653367
TI  - Prevalence and causes of severe taste loss in a chemosensory clinic population.
AB  - Although complete or near-complete olfactory loss has been extensively documented
      and described, few published reports have documented severe generalized gustatory
      loss (across qualities and neural fields) with rigorous psychophysical testing,
      and none have explored the prevalence or causes of such losses in a large
      clinical population. This study retrospectively reviews our chemosensory clinic's
      experience of 1,176 patients evaluated for complaints of chemosensory dysfunction
      in order to address these issues. Our series confirms that despite the complex,
      bilateral innervation and regenerative capacity of the gustatory system, severe
      generalized taste loss does occur as a clinical entity, albeit rarely: only 0.85%
      (n = 10) of our patients evidenced such a deficit, as compared to 32% (n = 371)
      who were found to have a profound olfactory deficit. Combinations of systemic
      and/or acute events may underlie many cases of severe taste loss, and in half of
      our cases, these patients evidenced moderate to complete smell loss as well.

PMID- 14653368
TI  - Histopathology of the inner ear in unoperated acoustic neuroma.
AB  - Although hearing loss is the most common presenting symptom in patients with
      acoustic neuroma, the pathophysiology of hearing loss associated with acoustic
      neuroma is unknown. Although primary dysfunction of the auditory nerve is
      intuitively logical, available histopathologic and clinical data suggest that
      although neural degeneration is common, it alone does not adequately account for
      hearing loss in many cases. The purpose of this study was to evaluate 11 cases of
      unoperated unilateral acoustic neuromas. Temporal bones were identified by means
      of a search mechanism provided by the National Temporal Bone, Hearing, and
      Balance Pathology Resource Registry and were prepared for light microscopy by
      standard techniques. Quantification of spiral ganglion cells, hair cells, stria
      vascularis, and spiral ligament was accomplished for each specimen. In addition,
      the maximum diameter and volume of each tumor were calculated from
      histopathologic sections. Increasing tumor size did predict a reduced spiral
      ganglion count. However, although there was a tendency for decreasing spiral
      ganglion cell count and for increasing tumor size to predict a higher pure tone
      average and lower speech discrimination score, these correlations did not reach
      statistical significance. In tumor ears in which the speech discrimination score
      was 50% or less, there was always significant degeneration of other structures of
      the inner ear in addition to neurons, including hair cells, the stria vascularis,
      and the spiral ligament. Endolymphatic hydrops and eosinophilic precipitate in
      the perilymphatic spaces were found in 2 of 3 such cases. It is concluded that
      acoustic neuromas appear to cause hearing loss, not only by causing degeneration
      of the auditory nerve, but also by inducing degenerative changes in the inner
      ear. It is hypothesized that the proteinaceous material seen histologically may
      represent the products of up-regulated genes in acoustic neuroma, some of which
      may interfere with normal cochlear function.

PMID- 14653369
TI  - Acoustic analysis of autologous fat injection versus thyroplasty in the same
      patient.
AB  - We objectively measured the acoustic effects of treatment of unilateral vocal
      fold paralysis by injection of autologous fat and by polytetrafluoroethylene
      thyroplasty, in the same patient. To our knowledge, this is the first report
      comparing the two techniques by using the patient's normal voice as the control.
      The voice of a male patient was recorded before and after onset of unilateral
      vocal fold paralysis, after treatment with autologous fat, and after
      polytetrafluoroethylene thyroplasty. Acoustic analysis was performed on a long
      term average spectrum of text and on the MDVP (Kay Elemetrics) evaluation of the
      vowel /a/. Jitter and shimmer were not normalized, but they improved to a greater
      extent after fat injection. The cepstral peak prominence, spectral skewness, and
      long-term average spectrum returned to preparalytic values after both treatments,
      but improved to a greater extent after fat injection. This study showed that both
      techniques can return the voice to preparalytic values. Spectral measurements
      best reflected the voice improvement. Further prospective studies in a larger
      number of patients will be necessary to confirm these results and to determine
      the long-term objective voice outcome obtained with these techniques.

PMID- 14653370
TI  - Treatment of idiopathic sudden sensorineural hearing loss with antiviral therapy:
      a prospective, randomized, double-blind clinical trial.
AB  - A subclinical viral labyrinthitis has been postulated in the literature to elicit
      idiopathic sudden sensorineural hearing loss (ISSHL). An etiologic role for the
      herpes family is assumed. Corticosteroids possess a limited beneficial effect on
      hearing recovery in ISSHL. In this study, we evaluated the therapeutic value of
      the antiherpetic drug acyclovir (Zovirax) on hearing recovery in 91 patients with
      ISSHL who received prednisolone in a prospective, randomized, double-blind,
      placebo-controlled, multicenter trial. The audiometric parameters included pure
      tone and speech audiometry. Subjective parameters studied included hearing
      recovery, a pressure sensation in the affected ear, vertigo, and tinnitus. A 1
      year follow-up was obtained. Hearing recovery for the whole group averaged about
      35 dB and was independent of the severity of the initial hearing loss or
      vestibular involvement. Speech audiometry improved from 49% to 75%. After 12
      months, pressure sensation and vertigo decreased to 15.6% (acyclovir) and 10.3%
      (placebo) and 12.5% (acyclovir) and 10.7% (placebo), respectively. Tinnitus
      decreased slightly, to 46.9% (acyclovir) and 55.2% (placebo), in the same period
      (p > .05 for all parameters). We conclude that no beneficial effect from
      combining acyclovir with prednisolone can be established in patients with ISSHL.

PMID- 14653371
TI  - Global injury 2000.

PMID- 14653372
TI  - Recognising and managing sickle cell crisis in the emergency department.

PMID- 14653373
TI  - Dead cattle, lead and child health.
AB  - This study was carried out as part of a larger interagency investigation in
      response to concerns about human health following the death of three cattle from
      lead poisoning in an old lead mining area in Silvermines, Tipperary. Its aim was
      to screen for lead toxicity in the local child population. Screening consisted of
      measurement of blood lead concentrations and the completion of questionnaires
      regarding exposure to lead and general health. Pre-school and primary school
      children resident in four surrounding district electoral divisions (DEDs) were
      specifically targeted. One out of 334 (0.3%) children screened had an elevated
      blood lead concentration. The geometric mean lead concentration was 2.6 microg/dl
      which is below the intervention lead concentration of 10 microg/dl recommended by
      the CDC. The mean lead concentration in those aged under three years was
      statistically significantly higher than in those aged three years and over (3.4
      microg/dl vs 2.5 microg/dl; p=0.000581). No specific health problems were
      identified by the questionnaires. This study concluded that the elevated
      environmental lead levels which were demonstrated by other agencies involved in
      this investigation are not currently being transferred to children. It recommends
      further blood screening of children in the area and ongoing education to minimise
      the risk of lead toxicity in the area in the future.

PMID- 14653374
TI  - Cost of treating stroke in an Irish teaching hospital.
AB  - In contrast to CHD and cancer, the burden of stroke lies with long term
      disability as opposed to death and it is the most common cause of neurological
      disability in the western world. Consequently such patients frequently require
      longer acute hospital stays followed by lengthy periods of rehabilitation where
      such services are available, long term nursing care or indefinite dependency on
      community care. Inevitably stroke is a major economic burden on healthcare
      systems. It has been estimated that approximately 6% of total healthcare
      resources are consumed in the management of this condition a figure which is
      expected to grow with an increasing elderly population. Due to the high level of
      disability caused by stroke, patients often require longer and therefore costly
      periods of acute hospital stay. The aim of this study is to determine the cost of
      treating an acute episode of ischaemic stroke in an Irish teaching hospital. The
      costing evaluation was from the hospital admission perspective and the strategy
      used was a microcosting detailed collection of resources used on patients
      admitted to St. James's hospital between January 1999 and March 2000. The average
      cost of a hospital admission for the treatment of an episode of acute ischaemic
      stroke was 6,722 euros. The average cost per day was calculated at 263 euros.
      Approximately 83% of hospital costs were associated with ward costs whereas
      medications accounted for just 1% of total costs. The projected cost for the
      treatment of stroke in euros using the consumer price index for October 2002
      would be 7,686 euros. The availability of Irish cost data is essential for the
      assessment of the cost effectiveness of therapeutic interventions for the
      treatment of stroke in our healthcare system.

PMID- 14653375
TI  - Lung cancer survival in Northern Ireland.
AB  - Lung cancer causes more deaths than any other cancer in Northern Ireland.
      Survival, and factors which could influence survival, were examined for the 4,458
      patients diagnosed with lung cancer from 1992 to 1996. Overall five-year relative
      survival was low, but better for females (9%) than males (7%). Survival improved
      each year although this could not be attributed to treatment changes. Survival
      was better for men under 65 years, than older men (p<0.01), while survival from
      non-small cell type lung cancer was better than small cell (p<0.001). The
      proportion of patients having bronchoscopy and CT scan increased over the study
      period. Although the proportion of patients receiving surgery or radiotherapy
      remained unchanged over the period there was an increase in the proportion
      receiving chemotherapy (8.7% vs. 9.4%, P<0.05). Survival rates, although slightly
      better than in the rest of the United Kingdom, were poorer than in several other
      countries, including the Republic of Ireland and the United States of America.
      High mortality rates from lung cancer and, at best, modest improvements in
      survival, point to the need for increased efforts to reduce levels of lung cancer
      by tackling the main cause, smoking.

PMID- 14653376
TI  - The anatomical distribution of cerebral gliomas in mobile phone users.
AB  - We analysed the association between mobile phone use and the anatomical
      distribution of glial brain tumours in Irish neurosurgical patients. All patients
      with unilateral histologically proven glioma were enrolled over a 12 month
      period. We hypothesised that were a cellular phone to cause a glioma then it
      would do so on the dominant hand side. Fifty mobile phone users and twenty three
      non-users were identified. The vast majority of patients (69/73) were right
      handed and the right side of the brain was more common as the tumour site
      (48/73). Fisher's exact test revealed no statistical significance for glioma
      location based on the handedness of the patient in the mobile phone user group
      and location of the tumour in both user and non-user groups. We discuss our
      findings and the stable trend in the incidence of reported glioma cases.

PMID- 14653377
TI  - The caesarean section rate in the Republic of Ireland in 1998.
AB  - The Caesarean section (CS) rate has risen dramatically in the United Kingdom and
      North America over the past 20 years. There are no recent data in the Republic of
      Ireland on CS rates. Our aim was to ascertain the national CS rate for the year
      1998. In addition, we sought to determine instrumental delivery rates and
      epidural rates. Twenty-two of 24 units replied to a questionnaire giving a
      response rate of 92%. The CS rate was 17.8% (12.8-26.7%), 7.5% were elective and
      10.3% were emergency. The size or type of the maternity unit did not influence
      the CS rate. The cause for the rise in the CS rate is multifactorial. Review of
      the current literature would suggest that a further rise in the CS rate in
      Ireland is likely.

PMID- 14653378
TI  - Unusual presentation of idiopathic deltoid contracture.

PMID- 14653379
TI  - Mucosal erosions and a cough.

PMID- 14653380
TI  - Disease-specific morbidity data at hospital-level: do they really matter?

PMID- 14653381
TI  - Folliculitis secondary to waxing for depilation--a cause for concern.

PMID- 14653382
TI  - Giant bladder diverticulum causing recurring urinary retention.

PMID- 14653383
TI  - Trends in blood transfusion in obstetrics at the National Maternity Hospital 1991
      2001.

PMID- 14653384
TI  - The tale of a blue toddler.

PMID- 14653385
TI  - Mitochondrial disorder with a common 4977-bp deletion presenting as a novel
      multisystem neurodegenerative disorder.

PMID- 14653386
TI  - Five-year clinical, microbiological, and radiological outcome following treatment
      of peri-implantitis in man.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term outcome of a
      combined surgical and antimicrobial treatment of peri-implantitis lesions in
      humans. METHODS: Nine partially dentate individuals with titanium implants
      demonstrating a marginal bone loss of > or = three threads as compared to
      baseline measurements made from 1-year intra-oral radiographs, bleeding on
      probing, and/or suppuration from the peri-implant sulci were included in the
      study. In each individual, subgingival bacterial samples were obtained and
      subjected to microbiological analysis by culture. Surgical exposure of the
      lesions and cleaning of the implants using hydrogen peroxide were performed. The
      patients were given systemic antibiotics according to a susceptibility test of
      target bacteria. The treatment was evaluated clinically, microbiologically, and
      radiograpically at 6 months, 1 year, and 5 years. RESULTS: Seven out of 26
      implants with peri-implantitis at baseline were lost during the 5-year follow-up
      period despite a significant reduction in the presence of plaque and gingival
      bleeding. Four implants continued to lose bone, 9 had an unchanged bone level,
      and 6 gained bone. Five of the patients were treated with antibiotics directed
      against putative periodontopathogens, i.e., A. actinomycetemcomitans, P.
      intermedia, or P. gingivalis; three patients were treated for presence of
      enterics (E. coli and E. cloace); and, in one patient, treatment was directed
      against S. aureus. CONCLUSIONS: Despite treatment and retreatment, seven implants
      were lost. However, the applied surgical and antimicrobial treatment strategy for
      advanced peri-implantitis lesions was successful in 58% of the implants treated
      during the 5-year follow-up period. Smoking seemed to be a negative risk factor
      for treatment success.

PMID- 14653387
TI  - Amelogenin: a potential regulator of cementum-associated genes.
AB  - BACKGROUND: Studies suggest that enamel matrix proteins induce differentiation
      and mineralization of a variety of mesenchymal cells, including odontoblasts,
      osteoblasts, and cementoblasts. It has been postulated that this activity could
      be due to amelogenin-like proteins, known to be present in some mixtures of
      enamel matrix derivatives. Amelogenins have been reported to induce expression of
      a mineralized tissue-specific marker, bone sialoprotein (BSP), indicating that
      epithelial products can regulate the activity of mesenchyme-derived cells.
      METHODS: To explore the molecular mechanisms involved in BSP regulation, a clonal
      population of immortalized murine cementoblasts (OCCM-30) was exposed to full
      length murine amelogenin protein (rp(H)M180), 0.1 microg/ml to 10.0 microg/ml,
      for 8 days in vitro. To further investigate the potential epithelial-mesenchymal
      interaction, an amelogenin knockout mouse model was used to examine expression of
      BSP and other markers, including Type I collagen, in tissue samples. RESULTS: The
      lowest dose of amelogenin slightly enhanced BSP expression, whereas at the
      highest dose, a dramatic decrease (three-fold) in BSP expression was observed.
      Parallel experiments showed a corresponding decrease in mineral nodule formation
      in vitro for cells treated with the higher dose of rp(H)M180. In situ
      hybridization and immunohistochemical analysis of sections from amelogenin null
      mice revealed a dramatic reduction in expression of BSP mRNA and protein in
      cementoblasts and surrounding osteoblasts in comparison to age-matched controls.
      In contrast, the expression of Type I collagen was not significantly different
      from controls. CONCLUSION: These data suggest that amelogenin may be a critical
      signaling molecule required for appropriate development of the periodontium.

PMID- 14653388
TI  - Antibody responses of periodontitis patients to gingipains of Porphyromonas
      gingivalis.
AB  - BACKGROUND: Arginine- and lysine-specific cysteine proteinases (arg-gingipain:
      Rgp, lys-gingipain: Kgp) are major virulence factors of Porphyromonas gingivalis.
      Recent reports have suggested that antibodies against gingipains can play a
      protective role against infection by P. gingivalis. The purpose of this study was
      to evaluate the IgG responses of patients with periodontitis to functional
      domains of gingipains. METHODS: A group of 29 periodontitis patients and 10
      periodontally healthy subjects (control group) were recruited into this study. We
      prepared three recombinant fragments of rgp A (catalytic domain; r-Rgp CAT) and
      two hemagglutinin domains (r-Rgp 44, and r-Rgps 15-27) corresponding to amino
      acid residues 228 to 719, 720 to 1136, and 1137 to 1704, respectively. One
      fragment of the Kgp catalytic domain (r-Kgp CAT) corresponding to amino acid
      residues 229 to 737 and expressed in Escherichia coli was also used. IgG antibody
      levels to these recombinant proteins in sera from the subjects were determined by
      an enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that IgG levels
      against r-Rgp 44 and r-Rgps 15-27 in sera obtained from the patients were
      significantly higher than those in the healthy group (P<0.01). In contrast, no
      significant differences in IgG levels against r-Rgp CAT and r-Kgp CAT were found
      between the control and patient groups. The IgG responses to P. gingivalis sonic
      extracts, r-Rgp 44 and r-Rgps 15-27, were related to probing depth in sera from
      patients, but those to r-Rgp CAT and r-Kgp CAT were not. CONCLUSION: The present
      findings suggest that the low responsiveness of IgG antibody against the
      catalytic domains of gingipain, r-Rgp CAT, and r-Kgp CAT is a key factor in
      infection by P. gingivalis.

PMID- 14653389
TI  - Nicotine stimulates osteoclast resorption in a porcine marrow cell model.
AB  - BACKGROUND: Combustible tobacco use is generally linked with accelerated
      periodontal bone loss and diminished post-surgical wound healing; however, the
      pathogenesis of this process at the cellular level remains unclear. Nicotine is
      known to affect human gingival fibroblast orientation, attachment, and beta1
      integrin expression, yet little is known about its effects on osteoclasts, the
      cells most responsible for bone resorption. The purpose of this study was to
      determine the effects of physiologically relevant nicotine levels on porcine
      osteoclast function as measured by resorption of calcium phosphate. METHODS: Pure
      nicotine was diluted in medium to the following concentrations: 0.03 microM, 0.15
      microM, 0.30 microM, 0.60 microM, and 1.50 microM. Porcine osteoclasts were
      seeded onto calcium phosphate multi-test slides and incubated at 37 degrees C
      with half media changes every 24 hours. Cells received 0, 0.15, 0.30, 0.60, and
      1.50 microM nicotine, or 25 nM parathyroid hormone (PTH). Osteoclast resorption
      was quantified by measuring the resorbed surface area of the calcium phosphate
      substrate. RESULTS: Osteoclast cultures resorbed bone slices and calcium
      phosphate substrate. All nicotine concentrations and PTH resulted in
      statistically significantly greater mean percent resorptions than the control
      group (P < 0.05). However, no statistical difference was found between the
      various nicotine doses or PTH. The number of osteoclasts increased in a linear
      relationship to the increasing nicotine concentrations; however, no correlation
      was found between osteoclast number and the amount of resorption. CONCLUSIONS:
      Nicotine is non-toxic to osteoclasts at the clinically relevant levels tested.
      Nicotine appears to stimulate osteoclast differentiation and resorption of
      calcium phosphate, the major component of bone. Nicotine-modulated osteoclast
      stimulation may, in part, explain the increased rapidity of periodontal bone loss
      and refractory disease incidence in smokers.

PMID- 14653390
TI  - Cross-talk between interleukin-6 and transforming growth factor-beta3 regulates
      extracellular matrix production by human fibroblasts from subjects with non
      syndromic cleft lip and palate.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) interference with
      interleukin 6 (IL-6) activity and the role of the latter in early human embryonic
      development prompted us to examine the effects IL-6 on matrix synthesis and the
      effects of TGF-beta3 on IL-6 expression human cleft lip and palate (CLP)
      fibroblasts. METHODS: Collagen and glycosaminoglycan (GAG) synthesis were
      determined by radiolabeled precursors and biglycan expression by Northern
      blotting before and after adding IL-6. The effects of TGF-beta3 on IL-6
      production were assayed by evaluating IL-6 transcript by Northern blotting and IL
      6 protein secretion by enzyme-linked immunosorbent assay. RESULTS: The results
      showed that IL-6 elicited an inhibitory effect on collagen and GAG levels in CLP
      fibroblasts by lowering hyaluronan and dermatan sulfate secretion. IL-6 up
      regulated biglycan expression, but less strongly than TGF-beta3. TGF-beta3
      significantly down-regulated IL-6 transcript and secretion in CLP fibroblasts.
      CONCLUSIONS: These data suggest the increase in matrix components that
      characterize the CLP fibroblast phenotype might be due to a concerted TGF-beta3
      IL-6 action. We hypothesize changes in cross-talk between TGF-beta3 and IL-6
      signal transduction pathways are involved in the induction of cleft palate.

PMID- 14653391
TI  - A comparative study on the effect of nicotine administration and cigarette smoke
      inhalation on bone healing around titanium implants.
AB  - BACKGROUND: A series of isolated studies has focused on the influence of smoking
      on bone around titanium implants. This study proposes to investigate the impact
      of two conditions, i.e., nicotine administration and cigarette smoke inhalation,
      on the healing around implants. METHODS: Forty-five Wistar rats were used. After
      anesthesia, the tibiae surface was exposed and a screw-shaped titanium implant
      was placed bilaterally. The animals were randomly assigned to one of the
      following groups: Group 1: control, n = 19; Group 2: intermittent cigarette smoke
      inhalation, n = 15; and Group 3: subcutaneous administration of nicotine (3
      mg/kg) twice daily, n = 11. After 60 days, the animals were sacrificed. The
      degree of bone-to-implant contact (BIC) and the bone area (BA) within the limits
      of the threads of the implant were measured in the cortical (zone A) and
      cancellous bone (zone B) areas. RESULTS: In zone A, cigarette smoke presented a
      significant negative influence on BIC and BA (Kruskal-Wallis test, P < 0.05). In
      contrast, the administration of nicotine did not influence either parameter (P >
      0.05). In zone B, cigarette smoke inhalation also resulted in a decreased
      percentage of BIC compared to the control group (P < 0.05). In addition, the BA
      was significantly decreased in groups 2 and 3 when compared to controls (P >
      0.05). CONCLUSION: The negative impact of smoking on implant outcomes may be
      related to more than one molecule present in the cigarette smoke and nicotine
      seems to partially contribute, especially in the cancellous bone.

PMID- 14653392
TI  - Prevalence of periodontopathic bacteria in aggressive periodontitis patients in a
      Japanese population.
AB  - BACKGROUND: Actinobacillus actinomycetemcomitans is considered a major etiologic
      agent of aggressive periodontitis. Other periodontopathic bacteria such as
      Porphyromonas gingivalis are also suspected of participating in aggressive
      periodontitis, although the evidence is controversial. The aim of the present
      study was to investigate the prevalence of periodontopathic bacteria and to
      clarify the microbiological features of aggressive periodontitis in Japanese
      patients. METHODS: Subgingival plaque was collected from 50 aggressive
      periodontitis (AgP) patients (localized 10, generalized 40). Samples from 35
      generalized chronic periodontitis (CP) patients and 18 healthy subjects were
      examined as controls. Plaque samples were examined using culture and polymerase
      chain reaction (PCR) method. RESULTS: The prevalence of A. actinomycetemcomitans
      was relatively low in the localized (20%) and generalized (17.5%) AgP patients,
      with no significant difference observed in detection frequencies between AgP and
      the control groups (CP 8.6%, healthy 0%). On the other hand, Tannerella
      forsythensis (formerly Bacteroides forsythus), Campylobacter rectus, P.
      gingivalis, and Treponema denticola were frequently detected in localized as well
      as generalized aggressive periodontitis patients. The prevalence and proportion
      of P. gingivalis correlated with severity of clinical attachment loss in both
      localized and generalized aggressive periodontitis. CONCLUSIONS: T. forsythensis,
      C. rectus, P. gingivalis, and T. denticola were the predominant periodontopathic
      bacteria of aggressive periodontitis patients in Japan. Although A. actinomycetem
      comitans was also detected in AgP patients, the prevalence of this bacterium was
      much lower than that of P. gingivalis.

PMID- 14653393
TI  - Periodontal referral patterns, 1980 versus 2000: a preliminary study.
AB  - BACKGROUND: A review of the periodontal literature offers little information
      concerning trends in referral patterns of patients for periodontal therapy. Over
      the last 2 decades, there has been a significant increase in the knowledge base
      concerning inflammatory periodontal disease. It might be assumed that the
      collective advances in knowledge have impacted periodontal referral patterns.
      Thus, the purpose of this study was to examine the differences in periodontal
      referral patterns in the same offices separated by a 20-year interval (i.e., 1980
      and 2000). METHODS: A retrospective chart analysis was conducted on a total of
      782 patient charts from three conveniently selected periodontal practices. Charts
      were randomly selected from two time periods: 1980-1981 and 2000-2001. The
      following information was obtained from each patient record: gender, age at time
      of initial examination, tobacco smoking status at time of initial examination,
      periodontal case type, number of missing teeth at initial examination (not
      including third molars), and number of teeth scheduled for extraction per
      periodontal treatment plan. Descriptive data were analyzed using frequency
      distributions, measures of central tendency, and measures of dispersion. Non
      parametric statistics were used to examine the relationship of disease severity
      as a function of site, time period, and patient age. RESULTS: The following
      trends were noted: 1) an increase in the average age of patients at the time of
      the initial examination; 2) a decrease in the percentage of patients using
      tobacco at the time of the initial interview; 3) an increase in the percentage of
      periodontal Case Type IV patients with a concomitant decrease in the number of
      periodontal Case Type II patients; 4) an increase in the average number of
      missing teeth per patient at the initial examination; and 5) an increase in the
      average number of teeth scheduled for extraction per periodontal treatment plan.
      CONCLUSIONS: Characteristics of patients referred in 1980 compared to those
      referred in the year 2000 indicate that, although fewer patients used tobacco,
      there were several noteworthy trends. At referral, patients exhibited a greater
      loss of teeth, had more severe disease, and required extraction of a greater
      number of teeth in 2000 compared to 1980. Possible reasons for these trends are
      discussed.

PMID- 14653394
TI  - Effect of tobacco smoking on neutrophil activity following periodontal surgery.
AB  - BACKGROUND: Tobacco smoking has considerable negative effects on the outcome of
      periodontal treatment. The reason for the inferior therapeutical effect might be
      related to an altered neutrophil activity in terms of elastase and/or matrix
      metalloproteinase-8 (MMP-8), as well as in the protease inhibitor alpha-1
      antitrypsin (alpha-AT) and alpha-2-macroglobulin (alpha-2-MG) activities. The aim
      of the present study, therefore, was to elucidate the effect of tobacco smoking
      on gingival crevicular fluid (GCF) levels of these substances following surgical
      treatment. METHODS: The study population included 15 smoking and 15 non-smoking
      patients with moderate to severe periodontitis receiving surgical treatment.
      Clinical examinations and collection of GCF were done prior to surgery and 1 and
      5 weeks following treatment. The elastase activity was measured with a
      chromogenic low-molecular substrate and the levels of alpha-1-AT, alpha-2-MG, and
      MMP-8 with enzyme-linked immunosorbent assay. RESULTS: The results showed
      unaltered levels of alpha-1-AT, alpha-2-MG, and MMP-8 in smokers following
      surgery. In non-smokers, the levels of alpha-1-AT and alpha-2-MG increased,
      whereas MMP-8 levels decreased. The levels of elastase remained unaltered in both
      smokers and non-smokers. CONCLUSIONS: These results indicate that in the presence
      of smoking, the levels of alpha-1-AT, alpha-2-MG, and MMP-8 remained unaltered
      during the recovery period following surgical treatment. This is interpreted as a
      possible interference of smoking with the treatment response and may, in part,
      explain the clinical evidence of an inferior treatment outcome in smokers.

PMID- 14653395
TI  - Bone-implant interface around titanium implants under different loading
      conditions: a histomorphometrical analysis in the Macaca fascicularis monkey.
AB  - BACKGROUND: Bone healing around endosseous dental implants is associated with
      peri-implant loading conditions. Therefore, the aim of this study was to evaluate
      histomorphometrically the bone response around unloaded, delayed, and immediately
      loaded implants with a progressive thread design that were placed in the
      posterior regions of the lower jaw in monkeys. METHODS: Nine adult monkeys
      (Macaca fascicularis) were used in this study. After extraction of the second
      premolars and first and second molars in the mandible, the bone was allowed to
      heal for a period of 3 months. Forty-eight 8 mm long implants with a diameter of
      3.5 mm were placed according to the following protocol. In two of the monkeys,
      six implants were placed and left to heal submerged for 3 months (group A). In
      seven monkeys, 21 implants were placed in one side of the mandible and loaded
      after 3 months of submerged healing (group B). The group B implants were loaded
      with temporary resin bridges at the same time as another 21 implants that were
      loaded immediately (group C) after placement in the contralateral side of the
      mandibles of the same monkeys. The occlusion of group B and C implants was
      checked for optimal relationship of the resin bridges that were replaced 1 month
      later with metal bridges and loaded for an additional 2 months. The group A
      animals were sacrificed after 3 months of submerged healing without loading;
      group B and C animals were sacrificed after 3 months of implant loading.
      Specimens were examined histologically and histomorphometrically. RESULTS: All
      implants osseointegrated without presenting any gap in the metal-bone interface.
      Compact cortical bone was found in contact with the implant surfaces. Group A
      implants demonstrated in the interface cancellous bone with loose connective
      tissue. Group B and C implants showed a thick cortical plate with extensive bone
      trabeculae formation. There was a significant difference in bone-to-implant
      contact (BIC) between the various loading conditions. No significant difference
      (P < 0.05) was found between groups B and C. There was an increased area of bone
      (BA) within the threads as well as around the apices of group B and C implants.
      CONCLUSIONS: Implant loading might have stimulated increased bone formation and
      thus may be a key factor in influencing positive osseointegration. In addition,
      immediately loaded implants may osseointegrate in a similar manner as delayed
      loaded implants.

PMID- 14653396
TI  - Associations of periodontal status with general health conditions and serum
      antibody titers for Porphyromonas gingivalis and Actinobacillus
      actinomycetemcomitans.
AB  - BACKGROUND: The purpose of the present study was to evaluate associations of
      periodontal status with general health conditions and with serum antibody titers
      for Porphyromonas gingivalis (Pg) and Actinobacillus actinomycetemcomitans (Aa)
      in a Japanese population. METHODS: Subjects (1,314) aged 40 years or older were
      recruited for the study. Their periodontal status was evaluated using the
      community periodontal index of treatment needs (CPITN). Records from general
      health examinations were used for the present analyses, including data on age,
      gender, body mass index, systolic and diastolic blood pressure (SBP/DBP); levels
      of serum alkaline phosphatase, total cholesterol, high-density lipoprotein
      cholesterol, triglyceride, fasting blood glucose, and C-reactive protein (CRP);
      counts of white blood cells (WBC) and platelets; smoking habit; and
      electrocardiogram recordings. Serum IgG antibody titers for Pg fimbrial antigens
      (IgG.Pg.Fim.), Pg whole-cell antigens (IgG.Pg.whol.), and Aa whole-cell antigens
      (IgG.Aa.whol.) were determined using enzyme-linked immunosorbent assay. The
      subjects were divided, according to their maximum CPITN codes, into four
      periodontal groups: max.CPITN-0/1/2, -3, -4, or -MS (missing sextant). RESULTS:
      Multivariable logistic regression analyses revealed significant associations of
      the max.CPITN-4 subjects who were males (odds ratio, OR: 2.03) or smokers (OR:
      1.73), or who had high diastolic blood pressure (OR: 1.27), high WBC (OR: 1.24),
      high serum CRP level (OR: 2.39) and high serum IgG.Pg.Fim. (OR: 1.17),
      IgG.Pg.whol. (OR:1.54), and IgG.Aa.whol. (OR: 1.19) titers. CONCLUSION:
      Significant associations between periodontal status and several health conditions
      were found in the adult population examined, including gender, smoking habit,
      diastolic blood pressure, white blood cell counts, C-reactive protein, and serum
      IgG antibodies to P. gingivalis fimbriae, IgG P. gingivalis whole cell, and IgG
      A. actinomycetemcomitans whole cell titers.

PMID- 14653398
TI  - Recurrent recalcitrant gingival hyperplasia and plasminogen deficiency: a case
      report.
AB  - BACKGROUND: Recurrent gingival hyperplasia due to plasminogen deficiency is a
      rare condition due to fibrin deposition in the connective tissue. Only eight
      cases have previously been reported in the English literature, and all cases were
      diagnosed before the age of 35 years. This paper presents an older patient with
      recurrent gingival hyperplasia due to plasminogen deficiency
      (hypoplasminogenemia). METHODS: A 59-year-old woman presented with recurrent
      gingival swelling of 6 years' duration. Multiple biopsies performed at various
      time periods were histologically reported to be gingival hyperplasia with chronic
      inflammation. Routine hematoxylin and eosin (H & E) staining and direct
      immunofluorescence were performed. RESULTS: H & E-stained sections showed
      subepithelial, eosinophilic, amorphous, acellular deposits. Direct
      immunofluorescence showed positive staining for fibrin, immunoglobulin (Ig) G,
      IgA, and IgM. Functional plasminogen and plasminogen activator inhibitor-1 assays
      were done and found to be deficient. A diagnosis of gingival hyperplasia due to
      plasminogen deficiency (hypoplasminogenemia) was rendered. CONCLUSIONS: Recurrent
      gingival hyperplasia due to plasminogen deficiency (hypoplasminogenemia) is a
      newly recognized and rare condition. H & E staining, direct immunofluorescence,
      and assessment of functional plasminogen levels are essential to differentiate
      this condition from other conditions in which subepithelial, eosinophilic,
      amorphous materials are deposited.

PMID- 14653397
TI  - Platelet concentrates: effects of calcium and thrombin on endothelial cell
      proliferation and growth factor release.
AB  - BACKGROUND: Clinical evidence suggests that platelet concentrate (PC) could have
      beneficial therapeutic effects on hard and soft tissue healing, due to the
      contents of growth factors (GFs) stored in the platelets. The objectives of this
      study were: 1) to determine the concentrations of platelet-derived growth factor
      BB (PDGF-BB), transforming growth factor-beta1 (TGF-beta1), vascular endothelial
      growth factor (VEGF), and basic fibroblast growth factor (bFGF) released from PCs
      and whole blood (WB), before and after the addition of various concentrations of
      calcium and thrombin, and 2) to assess the physiological importance of the
      released GFs on angiogenesis. METHODS: WB and PCs were harvested and prepared
      from three healthy volunteers. Enzyme-linked immunosorbent assay tests, specific
      for PDGF-BB, TGF-beta1, VEGF, and bFGF, were performed on WB and PC supernatants,
      collected before and 30 minutes after the addition of various concentrations of
      calcium and thrombin. The supernatants were also added to human umbilical vein
      endothelial cell (HUVEC) cultures in order to measure their effects on
      endothelial cell proliferation. RESULTS: Growth factor concentrations detected in
      PC supernatants were significantly greater (280% to 800% increase) than
      concentrations present in WB supernatants. Calcium and thrombin induced immediate
      GF release from PCs in a dose-dependent fashion. Furthermore, PC supernatants led
      to greater HUVEC proliferation rates than WB supernatants. However, there was no
      correlation between the concentrations of specific GFs and HUVEC proliferation
      rates. CONCLUSION: These results suggest that PCs could stimulate blood vessel
      formation. They also reinforce the relevance for using PCs in regenerative
      therapies.

PMID- 14653399
TI  - Granulocytic sarcoma of gingiva: an unusual case with aleukemic presentation.
AB  - BACKGROUND: Granulocytic sarcoma (GS) is an uncommon extramedullary tumor
      composed of dense aggregates of immature myeloid precursor cells, which is
      usually associated with acute or chronic myeloid leukemia. The tumor may also be
      a predecessor to acute myeloid leukemia (AML). It may be found in any location
      throughout the body; however, intraoral occurrence is extremely rare. This report
      describes a case of gingival granulocytic sarcoma that developed prior to AML in
      a 12-year-old female. METHODS AND RESULTS: The patient, who had a 3-month history
      of gingival enlargement, was diagnosed as having granulocytic sarcoma based on
      clinical, radiological, and histological findings. Although the tumor regressed
      significantly after two induction chemotherapy courses, the patient subsequently
      died due to pneumococcal sepsis and pleurisy. CONCLUSION: This case report
      affirms the importance of granulocytic sarcoma in the differential diagnosis of
      gingival enlargements, since the tumor may occur before bone marrow involvement
      by leukemic cells.

PMID- 14653400
TI  - Guided tissue regeneration-based root coverage: meta-analysis.
AB  - BACKGROUND: The goal of guided tissue regeneration-based root coverage (GTRC) is
      to repair gingival recession via new attachment formation. Numerous clinical
      trials have been conducted utilizing the concept of GTR to promote root coverage.
      Most GTRC studies have had relatively small sample sizes and have not utilized
      power calculations to determine appropriate sample size; therefore, it is
      difficult to draw strong conclusions from them. Hence, the purpose of this study
      is to combine data from currently available GTRC studies and to use meta-analysis
      to determine whether GTRC provides significantly improved clinical outcomes
      compared to conventional periodontal plastic surgical approaches for the
      treatment of marginal tissue recession. METHODS: Studies were identified that
      used GTR approaches to treat gingival recession from January 1990 to October
      2001. Information from each study was entered into a database. Data were analyzed
      according to the following criteria: GTRC versus conventional mucogingival
      surgery (CMGS); membrane type; root conditioning; pretreatment recession depth;
      adjunctive use of bone replacement graft (BRG); and source of funding. Studies
      were ranked independently, and mean data from each were weighted accordingly.
      Meta-analysis was performed using the weighted means for each group. Paired t
      tests were used to determine statistical significance between each pair of
      groups. RESULTS: Forty papers were included for analysis. GTRC resulted in an
      average of 74% recession depth reduction, 41% complete root coverage, 3 mm AL
      gain, and 1 mm KG gain. Both GTRC and CMGS produced significant (P < 0.05)
      improvement compared to baseline measurements. Compared to GTRC, CMGS resulted in
      significantly (P < 0.05) increased KG (2.1 mm vs. 1.1 mm), root coverage (81% vs.
      74%), and percentage of defects with complete root coverage (55% vs. 41 %). Use
      of absorbable membranes, root conditioning, shallow pretreatment recession (< 4
      mm), and corporate sponsorship all resulted in significantly (P < 0.05) improved
      percentages of sites with complete root coverage but had no effect on other
      parameters. CONCLUSIONS: Based on this meta-analysis, guided tissue regeneration
      based root coverage can be used successfully to repair gingival recession
      defects. Conventional mucogingival surgery, however, resulted in statistically
      better root coverage, width of keratinized gingiva, and complete root coverage.

PMID- 14653401
TI  - A simplified classification and repair system for sinus membrane perforations.
AB  - A classification and repair system is presented for the management of sinus
      membrane perforations, based upon membrane location and severity. The results of
      19 consecutively treated cases are presented. All cases of sinus membrane
      perforation were appropriately managed, resulting in successful sinus
      augmentation therapy, implant placement, and restoration. All implants were
      functioning successfully at the time of statistical compilation.

PMID- 14653402
TI  - A referral-based periodontal practice--yesterday, today, and tomorrow.

PMID- 14653403
TI  - Position paper: oral features of mucocutaneous disorders.
AB  - Part of periodontology involves the diagnosis and treatment of a variety of non
      plaque-related diseases of the periodontium. The International Workshop for a
      Classification of Periodontal Diseases and Conditions noted that the periodontist
      may be called upon to manage non-plaque-related mucocutaneous disorders either
      alone, or as part of a treatment team consisting of physicians, dentists or other
      allied health care professionals. This informational paper will review the
      etiology, clinical manifestations, diagnosis, and treatment of the most common
      chronic mucocutaneous diseases, including those that may present as desquamative
      gingivitis or intraoral vesiculobullous lesions. This paper is intended for the
      use of periodontists and other members of the dental profession.

PMID- 14653404
TI  - Friedreich ataxia.
AB  - There has been rapid progress in the understanding of several aspects of
      Friedreich's ataxia (FA) since the gene mutation was identified in 1996. At the
      clinical level, now it is possible to confirm that the majority of patients
      fullfilling clinical criteria for classic FA have the FA gene mutation but some
      do not, indicating genetic heterogeneity. Also, the phenotype associated with the
      FA mutation is much wider than that defined by clinical criteria and includes
      ataxia with retained or brisk reflexes as well as late onset ataxia with or
      without retained reflexes. It is now clear that the unstable GAA expansion that
      underlies FA causes a deficiency of the mitochondrial protein frataxin, leading
      to potentially harmful oxidative injury associated with excessive iron deposits
      in mitochondria. In addition, pathogenesis may involve a primary defect in
      synthesis of iron-sulfur cluster containing enzymes. Therapeutic attempts are
      already using anti-oxidant strategies and such efforts are likely to be enhanced
      by the rapid availability of animal models of the disease.

PMID- 14653405
TI  - Ataxia-telangiectasia: diagnosis and treatment.
AB  - Much progress has been made in the early diagnosis of ataxia-telangiectasia since
      the gene was cloned in 1995, A clinical diagnosis can now be confirmed by
      radiosensitivity testing (colony survival assay), immunoblotting, and mutation
      detection. The diagnostic value of serum alpha-fetoprotein levels and
      radiosensitivity has been reevaluated using patients with diagnoses based on the
      presence of mutations in the ATM gene and the absence of ATM protein in nuclear
      extracts. Little progress has been made in treating the progressive ataxia.

PMID- 14653406
TI  - Rare forms of autosomal recessive neurodegenerative ataxia.
AB  - There has been a recent explosion in knowledge regarding the genetic basis of
      several autosomal recessive ataxias. This article summarizes current information
      regarding rare forms of recessive ataxias. Friedreich's ataxia and ataxia
      telangiectasia are dealt with in other articles in this issue. The rarer
      recessive ataxias can be clinically classified as sensory and spinocerbellar
      ataxias, cerebellar ataxia with sensory-motor polyneuropathy, and purely
      cerebellar ataxias. Examples of the first category include ataxia with isolated
      vitamin E deficiency, abetalipoproteinemia, Refsum's disease, infantile-onset
      spinocerebellar ataxia, and ataxia with blindness and deafness. Examples of
      ataxia with sensory-motor polyneuropathy include ataxia with oculomotor apraxia 1
      and 2 and spinocerebellar ataxia with neuropathy 1. Examples of purely cerebellar
      ataxia include autosomal recessive spastic ataxia of Charlevoix-Saguenay and
      ataxia with hypogonadotropic hypogonadism. This review summarizes the clinical
      and genetic features of these entities and concludes that the pathogenic basis of
      such ataxias at this time appear to involve two broad types of processes: free
      radical injury and defects of DNA single- or double-strand break repair.

PMID- 14653407
TI  - Metabolic disorders causing childhood ataxia.
AB  - Ataxia is a common neurologic finding in many disease processes of the nervous
      system, and has classically been associated with numerous metabolic disorders. An
      error of metabolism should be considered when the ataxia is either intermittent
      or progressive. Acute exacerbation or worsening after high protein ingestion,
      concurrent febrile illness, or other physical stress is also suggestive. A
      positive family history can be an important diagnostic clue. Progressive
      molecular and biochemical techniques are revolutionizing this area of medicine,
      and there has been rapid advancement in understanding of the disease processes.

PMID- 14653408
TI  - Mitochondrial disorders and ataxia.
AB  - Mitochondrial disorders are important causes of progressive ataxia in children.
      Clinical examination, metabolic studies, imaging studies, muscle biopsies, and
      mitochondrial DNA studies are required to arrive at a specific diagnosis. There
      is poor correlation between phenotype and genotype in mitochondrial disorders.
      Ataxia is a major clinical presentation in Kearns-Sayre syndrome; mitochondrial
      encephalomyopathy with lactic acidosis and stroke-like episodes; myoclonic
      epilepsy with ragged-red fibers; neurogenic muscle weakness, ataxia, and
      retinitis pigmentosa; Leigh's syndrome; and coenzyme Q10 deficiency.

PMID- 14653409
TI  - Dominantly inherited ataxias.
AB  - The autosomal dominant ataxias continue to bewilder us as the enormity of their
      genetic heterogeneity continues to unfold. The Human Genome Organization website
      now lists 22 such ataxias, not including dentatorubral-pallidoluysian atrophy.
      The early genetic discoveries in this field included several disorders caused by
      CAG repeat expansions within coding regions of the respective genes. More recent
      discoveries have included unstable expansions of nucleotide repeats in noncoding
      regions of genes as well as point mutations that have formed the basis of
      progressive dominant ataxias. This article summarizes the clinical and genetic
      features of the currently identified dominant ataxias.

PMID- 14653410
TI  - Genetic testing in inherited ataxias.
AB  - Many genetic conditions can result in ataxia. Careful clinical, radiologic, and
      genetic evaluation permits the specific diagnosis of many of these conditions,
      which in turn facilitates medical care for the patient and genetic counseling for
      the patient and family. Predictive, prenatal, and carrier testing are possible
      for some conditions, but the use of gene tests in these clinical situations
      requires detailed genetic counseling that may be best left to genetics
      specialists.

PMID- 14653411
TI  - The changing epidemiology of esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma has risen rapidly over the past 3
      decades. This increase had been most dramatic among white men. It has supplanted
      squamous cell carcinoma as the predominant histologic type of esophageal cancer
      in the United States. The reasons underlying this phenomenon are not readily
      apparent. Improvements in diagnostic techniques and changes in cancer
      classification may explain some of the rise in reported incidence rates, but
      detection bias and misclassification bias do not appear adequate to explain the
      increase entirely. Risk factors for esophageal adenocarcinoma are reviewed, with
      particular emphasis on their role in underlying the rising cancer incidence. The
      etiologic factors most likely to explain the current epidemic of esophageal
      adenocarcinoma are the parallel epidemic of obesity, rising use of lower
      esophageal sphincter-relaxing medications, decreasing Helicobacter pylori
      infection, changes in the Western diet, and distant smoking habits.

PMID- 14653412
TI  - Barrett's esophagus and risk of esophageal adenocarcinoma.
AB  - Barrett's esophagus is most often seen in white men with chronic heartburn who
      are generally older than 50 years of age. The prevalence of Barrett's esophagus
      is 10% to 15% in patients who are undergoing endosocopy for gastroesophageal
      reflux disease and 1% to 2% in asymptomatic American adults. Barrett's esophagus
      represents metaplastic columnar tissue with specialized intestinal metaplasia,
      and this condition carries an increased risk of esophageal adenocarcinoma.
      Patients with Barrett's esophagus have a risk of esophageal adenocarcinoma 30 to
      60 times that of the general population with an incidence rate of over 100 times
      that of the general population. Esophageal adenocarcinoma has increased
      dramatically over the past few decades with specialized intestinal metaplasia
      being the most important risk factor for the development of dysplasia and cancer.
      Barrett's esophagus develops in the presence of persistent gastroesophageal
      reflux, which is an independent risk factor for adenocarcinoma. Other risk
      factors for adenocarcinoma in patients with Barrett's esophagus include length of
      Barrett's epithelium, low-grade dysplasia, and high-grade dysplasia. New data
      concerning the pathophysiology and biology of Barrett's epithelium may provide
      answers to prevent or treat esophageal cancer. This article briefly reviews
      Barrett's esophagus and focuses on the risk factors associated with its
      progression to adenocarcinoma.

PMID- 14653413
TI  - Early diagnosis of esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma has increased dramatically in
      developed countries during the past 2 decades, and prognosis remains very poor.
      Gastroesophageal reflux disease is an important risk factor for this cancer that
      develops in patients with specialized esophageal metaplasia (Barrett's
      esophagus). Careful periodic endoscopic examinations, with random biopsy sampling
      of the entire mucosal surface, are usually recommended for the surveillance of
      these patients. Several innovative techniques have recently been developed to
      improve the accuracy of diagnosis of intestinal metaplasia, dysplasia, and early
      adenocarcinoma in Barrett's esophagus. Some of these techniques (eg,
      chromoendoscopy, magnifying endoscopy, and light-induced fluorescence endoscopy)
      are intended to identify suspicious areas of the mucosa not visible during
      conventional endoscopic examination and to perform targeted biopsies toward these
      areas to avoid sampling errors. Optical coherence tomography and confocal laser
      scanning microscopy are other powerful techniques that provide real-time cross
      sectional tissue images at a resolution close to that of histology. They allow
      tissue characterization based solely on optical properties and are likely to
      replace excisional biopsies. Although promising, none of these techniques is
      currently recommendable for routine surveillance of patients with Barrett's
      esophagus. Further evaluation is warranted to define the optimal method and
      standardize the procedures.

PMID- 14653414
TI  - Staging esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma has increased dramatically in Western
      societies over the last 20 years. Most patients present with advanced disease.
      Stage-dependent treatment protocols require the most complete and accurate
      staging possible. With all esophageal cancers (ie, adenocarcinomas and squamous
      carcinomas), it is perhaps most important to identify patients who are unlikely
      to benefit from aggressive treatment. The performance characteristics and
      clinical utility of CT scanning, endoscopic ultrasound, FDG-PET, and minimally
      invasive surgery in staging esophageal cancer are reviewed, including issues
      relating specifically to staging of adenocarcinomas. These investigations are not
      mutually exclusive and each has its own strengths and shortcomings. Accurate
      staging often requires the use of multiple modalities. The optimal staging
      algorithm for a given practice setting (if it exists) will be determined largely
      by local variables that include patient population, available technology, and
      local expertise in applying such technology. A lack of consensus on the
      effectiveness of therapeutic alternatives (particularly surgical v nonsurgical
      methods) may also affect the perceived value of the various staging modalities
      and how they are used.

PMID- 14653415
TI  - Are perfusion technology and perfusionists ready for quality reporting employing
      six-sigma performance measurement?

PMID- 14653416
TI  - History of extracorporeal circulation: the conceptional and developmental period.
AB  - The development of modern techniques in extracorporeal circulation is the result
      of the combined efforts of physiologists, physicians, and engineers. Early
      experimental work at the end of the 19th century was accomplished by
      physiologists, such as von Schroder, von Frey, and Gruber, as well as Jacobj.
      These scientists laid the foundation for three different artificial oxygenation
      devices for experimental isolated animal organ perfusion. The developed bubble,
      film, and isolated lung oxygenation methods developed were later used for the
      first clinical cardiopulmonary bypass procedures in humans. For continuous
      perfusion experiments, closed circulation circuits were put into use. In a second
      step, during the first half of the 20th century, scientists and physicians, such
      as Brukhonenko, Gibbon, Crafoord, Bjork, and Jongbloed were working on the
      refinement of these methods for intended application during cardiovascular
      operations in humans. Refined bubble and film oxygenators together with the
      modern blood pumps in closed circulatory systems were assembled as pump
      oxygenators, later called heart-lung machines. They were used in the first
      clinical cases of extracorporeal circulation for heart surgery in the second half
      of the 20th century by Dennis, Dogliotti and Constantini, and Gibbon.

PMID- 14653417
TI  - History of extracorporeal circulation: the invention and modification of blood
      pumps.
AB  - The first roller pump was patented in 1855 by Porter and Bradley and was hand
      operated. A modification first named "surgical pump", designed and manufactured
      by E. E. Allen in 1887, was intended for direct blood transfusion. Truax, who
      also distributed and promoted the Allen pump with one roller, developed the first
      double roller pump in 1899. In the following decades, several researchers,
      including Beck, Van Allen, Bayliss and Muller as well as Henry and Jouvelet,
      refined the apparatus and recommended the use of roller pumps for blood
      transfusion and other applications. After further modifications made by DeBakey
      in 1934, and application of this pump in one of the first heart-lung machines
      constructed by Gibbon, DeBakey's name became inseparably attached to this type of
      pump. For perfusion experiments, an electrically powered roller pump was first
      used by Fleisch in 1935. Today, the roller pump is the most frequently used blood
      pump for cardiopulmonary bypass worldwide, having prevailed against the early
      pulsatile tube compression pumps and ventricular pumps. In recent years,
      centrifugal pumps have increasingly competed with roller pumps as systemic blood
      pumps for cardiopulmonary bypass and have become the preferred arterial pump in a
      variety of centers. Application of mechanical cardiac assistance has evolved from
      nonpulsatile roller pump support, followed by an era of pulsatile ventricular
      pumps to the rediscovery of the nonpulsatile flow mode with modern axial flow
      pumps.

PMID- 14653418
TI  - New Zealand's first open heart operation.

PMID- 14653419
TI  - Conversion from extracorporeal membrane oxygenation to total cardiopulmonary
      bypass: a simplified method.
AB  - Pediatric patients who have preoperative hemodynamic instability or postoperative
      cardiac decompensation may frequently require the use of extracorporeal membrane
      oxygenation (ECMO) for stabilization of cardiac and respiratory function. While
      ECMO can be a therapeutic treatment for the congenital pediatric patient, it does
      not allow the additional functions of a complete cardiopulmonary bypass (CPB)
      circuit should subsequent surgical revision in the operating room be required.
      This paper will discuss our approach to converting the ECMO circuit to total
      cardiopulmonary bypass allowing the use of cardioplegia, cardiotomy suction, and
      modified ultrafiltration. This technique allows the conversion to CPB without
      ceasing support to the critically ill patient or exposing them to additional
      blood products or surface area in the priming of a new extracorporeal circuit. In
      addition, this circuit design allows for the resumption of ECMO support utilizing
      the same circuit if the patient necessitates it.

PMID- 14653420
TI  - Bioreactors for tissue engineering--a new role for perfusionists?
AB  - Tissue engineering is an exciting new area of medicine with rapid growth and
      expansion over the last decade. It has the potential to have a profound impact on
      the practice of medicine and influence the economic development in the industry
      of biotechnology. In almost every specialty of medicine, the ability to generate
      replacement cells and develop tissues will change the focus from artificial
      organs and transplantation to growing replacement organs from the patient's own
      stem cells. Once these organs are at a size that requires perfusion to maintain
      oxygen and nutrient delivery, then automated perfusion systems termed
      "bioreactors" will be necessary to sustain the organ until harvesting. The design
      of these "bioreactors" will have a crucial role in the maintenance of cellular
      function throughout the growth period. The perfusion schemes necessary to
      determine the optimal conditions have not been well elucidated and will undergo
      extensive research over the next decade. The key to progress in this endeavor
      will development of long-term perfusion techniques and identifying the ideal
      pressures, flow rates, type of flow (pulsatile/nonpulsatile), and perfusate
      solution. Perfusionists are considered experts in the field of whole body
      perfusion, and it is possible that they can participate in the development and
      operation of these "bioreactors." Additional education of perfusionists in the
      area of tissue engineering is necessary in order for them to become integral
      parts of this exciting new area of medicine.

PMID- 14653421
TI  - Modified ultrafiltration postextracorporeal membrane oxygenation.
AB  - Modified ultrafiltration (MUF) has been widely used for the removal of
      extracellular water in the immediate postcardiopulmonary bypass (CPB) period. The
      reported benefits of this technique are improved hematological status and
      hemodynamic stability post-CPB, as well as a decrease in blood utilization during
      the operation. MUF has also been associated with improved pulmonary status along
      with enhanced myocardial performance. With these benefits in mind, we have
      explored the possible advantages of using MUF following extracorporeal membrane
      oxygenation (ECMO). The theoretical advantages of using MUF post-ECMO are the
      reduction of blood use prior to removal from ECMO for optimization of hemoglobin
      levels, improved pulmonary compliance decreasing the duration of ventilatory
      support, improved myocardial function, as well as the other reported benefits
      described with MUF post-CPB. This report communicates the technique used to
      perform MUF post-ECMO, as well as a simple MUF circuit design for use in the
      intensive care unit setting.

PMID- 14653422
TI  - Limitations using the vacuum-assist venous drainage technique during
      cardiopulmonary bypass procedures.
AB  - Vacuum-assist venous drainage (VAVD) can increase venous blood return during
      cardiopulmonary bypass (CPB) procedures. However, the negative pressure created
      in the closed cardiotomy reservoir can be transmitted to the oxygenator if a
      nonocclusive or centrifugal arterial pump is used, resulting in bubble
      transgression (BT) from the gas to blood compartment of the oxygenator. We
      analyzed the vacuum pressure required to produce BT using an in vitro circuit
      including successively a closed reservoir, a pump (centrifugal or roller), and an
      oxygenator. A constant hydrostatic pressure was maintained onto the oxygenator.
      Vacuum was applied on the cardiotomy reservoir, progressively increasing negative
      pressure from 0 to -80 mmHg and monitoring BT with a bubble detector. Six
      different oxygenators were compared. A partially occlusive roller pump and a
      centrifugal pump were compared to a control, which was without any pump. A mean
      negative pressure of -53 +/- 7 mmHg was necessary to produce BT in all the
      oxygenators in the absence of a pump. The presence of a centrifugal pump between
      the reservoir and the oxygenator significantly increased the negative pressure
      required to produce BT compared to the control (-67 +/- 7 mmHg, p < .05). No
      bubbles were detected using the roller pump (> -80 mmHg needed for BT), thus
      statistically significant when compared to the centrifugal pump (p < .05). The
      centrifugal pump offers significant resistance to BT but not as much compared to
      the roller pump, though BT cannot be prevented if the pump is turned off while
      the vacuum remains on the reservoir. Therefore, VAVD is a safe technique as long
      as the perfusionist stops the vacuum when the arterial pump is no longer in use.

PMID- 14653423
TI  - Hand-held personal digital assistant program for the HEMOCHRON RxDx heparin and
      protamine dosing system.
AB  - The use of in vitro dosing assays for heparin and protamine during cardiac
      surgery has significantly improved overall postoperative patient outcome. The
      HEMOCHRON RxDx system (International Technidyne Corp, Edison, NJ) is widely used
      for anticoagulation management. Based on a series of consecutive in vitro tests,
      the RxDx system is used to quantify the patient's heparin requirement (heparin
      response test, HRT), measure the activated clotting time (ACT), calculate the
      blood heparin concentration and the required protamine dose (protamine response
      test, PRT), as well as determine the efficacy of heparin reversal (protamine dose
      assay, PDA-O). A hand-held personal digital assistant (PDA) program has been
      developed that performs the RxDx calculations used for anticoagulation management
      during cardiac surgery. The Palm m505 hand-held device (Palm, Inc., Santa Clara,
      CA) is used in concert with any standard Hemochron blood coagulation system. The
      Palm m505 device has been programmed to perform all the calculations required for
      the RxDx test system. Patient's body weight, height, and gender are entered into
      the program using the onscreen keypad and the template provided in the Hemochron
      program. The calculator automatically provides the patient's blood volume and the
      recommended heparin dose upon entering the baseline ACT and HRT values and a
      target ACT. At the end of the case, the optimal protamine dose is determined, and
      the total heparin level is calculated and displayed upon entry of ACT and PRT
      clotting times. Following protamine administration, the program calculates any
      additional protamine required to neutralize residual heparin using the data from
      a PDA-O test. The RxDx hand-held PDA is accurate, quick, simple, and easy to use,
      patient data are saved and can be retrieved. The inclusion of this rapid
      computing technology into the Hemochron RxDx system serves to expand the
      applications of the Hemochron RxDx system during cardiac interventions.

PMID- 14653424
TI  - Membrane oxygenator exhaust capnography for continuously estimating arterial
      carbon dioxide tension during cardiopulmonary bypass.
AB  - Typically, the standard practice for measuring the arterial blood carbon dioxide
      tension (PaCO2) during cardiopulmonary bypass (CPB) is to take intermittent blood
      samples for analysis by a bench blood gas analyzer. Continuous inline blood gas
      monitors are available but are expensive. A potential solution is the capnograph,
      which was evaluated by determining how accurately the carbon dioxide tension in
      the oxygenator exhaust gases (PECO2) predicts PaCO2. A standard capnograph
      monitoring line was attached to the exhaust port of the membrane oxygenator.
      During CPB, the capnograph reading and arterial blood temperature were recorded
      at the same time as routine arterial blood gases were taken. One hundred fifty
      seven blood samples were collected from 78 patients. A good correlation was found
      between the PECO2 and the temperature corrected PaCO2 (r2 = 0.833, P < .001).
      There was also a reasonable degree of agreement between the PECO2 and the
      temperature corrected PaCO2 during all phases of CPB: accuracy (bias or mean
      difference between PaCO2 and PECO2) of -1.2 mmHg; precision (95% limits of
      agreement) of +/- 4.7 mmHg. These results suggest that oxygenator exhaust
      capnography may be a simple and inexpensive adjunct to the bench blood gas
      analyzer in continuously estimating PaCO2 of a clinically useful degree of
      accuracy during CPB.

PMID- 14653425
TI  - A model of venous return while utilizing vacuum assist during cardiopulmonary
      bypass.
AB  - In order for vacuum-assisted venous return (VAVR) to be used safely and
      efficiently during cardiopulmonary bypass (CPB), a full understanding of venous
      return is necessary. The focus of this work was to use the concepts of energy
      conservation and viscous energy dissipation in the development of a theoretical
      model of venous return utilizing vacuum assist. The effectiveness and accuracy of
      this model has been verified through in vitro laboratory investigations and
      statistical analysis. Although VAVR can provide higher flows through smaller
      venous cannula, vacuum assist may lead to increased levels of wall shear stress
      as shown in this work. The clinical implications of VAVR have yet to be
      investigated, but may lead to an exacerbation of the detrimental effects of CPB
      during cardiac surgery.

PMID- 14653426
TI  - Unique considerations for the spinal cord injured patient undergoing cardiac
      surgery utilizing cardiopulmonary bypass.
AB  - A 37-year-old male with mitral valve regurgitation presented for mitral valve
      replacement. He has been a C5 quadriplegic for 13 years. The patient had been
      discharged 2 months before to this admission after a complicated hospital course
      for Staphylococcus aureus infection of the left hip. His course was complicated
      by adult respiratory distress syndrome (ARDS) requiring prolonged intubation,
      acute renal failure (ARF) requiring dialysis, 10-day coma, and bacterial
      endocarditis now requiring mitral valve replacement. After initial stabilization
      with antibiotics and gradual improvement of the multiorgan system failure, the
      patient presented for valve replacement and worsening congestive heart failure
      (CHF). Para- and quadriplegic patients rarely undergo cardiac surgery requiring
      cardiopulmonary bypass (CPB). The explanation for this low incidence of heart
      surgery in this patient population ranges from physiologic changes from the
      spinal cord injury to their relatively short life span. Therefore, there is no
      vast knowledge of how these patients with spinal cord injury will physiologically
      respond to CPB. Chronic paraplegia presents unique anesthetic and perfusion
      challenges. General anesthesia for a patient with prolonged spinal cord damage
      can be difficult because of dysreflexia, muscle wasting, and potassium changes
      with depolarizing muscle relaxants. For the perfusionist, chronic paraplegia also
      accentuates hemodynamic responses to nonpulsatile flow with low peripheral
      vascular resistance common and difficult to treat. Dramatic increases in
      circulating catecholamine levels are a secondary result of the initiation of CPB
      that can cause a hypo- and hypertensive state. Depending on the level of spinal
      cord injury, one might expect acute hypo- or hypertension with the various phases
      of open-heart surgery and CPB. A viscous circle may occur because the
      hypertensive state is exaggerated because of inhibitory signals not passed below
      the spinal cord lesion and, therefore, the vasoconstrictive reflex continues
      unabated. The attack usually occurs abruptly and can lead to cerebrovascular
      hemorrhage and death if not controlled. Fortunately, we found this patient did
      not develop mass autonomic dysreflexia and was not difficult to wean from CPB.
      The problems associated with spinal cord injury present potential complications
      to this patient population. Numerous triggering mechanisms may lead to a variety
      of clinical complications. Consideration of a response/ treatment management plan
      for potential problems must be exercised by the surgical team.

PMID- 14653427
TI  - Psychosis in elderly patients: classification and pharmacotherapy.
AB  - Psychosis in elderly patients is a growing clinical concern because psychotic
      symptoms most frequently occur as noncognitive manifestations of Alzheimer's
      disease, as side effects of drug therapy for Parkinson's disease, or as the
      primary abnormalities in schizophrenia, and the clinical characteristics of
      psychosis are distinct for each. In planning antipsychotic pharmacotherapy for
      elderly patients, age-related pharmacokinetic changes, polypharmacy for comorbid
      diseases, and concerns about the underlying conditions responsible for the
      psychotic symptoms must be considered. Traditional antipsychotic agents bind to
      dopamine receptors and effectively relieve positive schizophrenic symptoms but
      frequently cause tardive dyskinesia and other extrapyramidal symptoms, a problem
      for elderly patients, particularly for those with Parkinson's disease. Atypical
      antipsychotics bind to dopamine and serotonin receptors, relieving both positive
      and negative symptoms, and are less likely to cause extrapyramidal symptoms. The
      authors review common diagnostics associated with psychosis in the elderly and
      clinical guidelines to selecting antipsychotic pharmacotherapy.

PMID- 14653428
TI  - The biology of psychosis in older people.
AB  - The nosology, classification, and biological basis of psychosis in the elderly
      have been much debated. Psychotic features are seen in schizophrenia, affective
      illness, and dementia in the elderly. This article reviews evidence for the
      biological basis of psychosis in older people. In schizophrenia, there is
      evidence of gender differences in brain volume loss and dopamine receptor
      numbers, possibly linked to estrogen loss in women. Neuroimaging evidence of
      ventricular brain changes and more dopamine receptors have also been documented.
      In Alzheimer's disease, genetic factors such as PS1 and ApoE4 have been
      associated with psychotic symptoms, and histopathological studies have revealed
      differences in neuronal pathology. Radiological studies have shown right and left
      hemisphere differences in size, blood flow, and glucose metabolism between
      psychotic and nonpsychotic patients. In affective illnesses, there is evidence of
      structural brain changes in psychotic depression. Ample evidence suggests that
      biological substrates underlie many psychotic symptoms. More research will
      identify causal links between brain changes, symptom appearance, and the effects
      of psychosocial factors in their genesis.

PMID- 14653429
TI  - Pharmacologic management of psychosis in the elderly: a critical review.
AB  - OBJECTIVE: Psychotic symptoms are seen in numerous psychiatric illnesses
      afflicting the elderly. This article reviews the efficacy of the pharmacologic
      management of psychotic symptoms in primary psychotic disorders, affective
      disorders, and neurodegenerative disorders. METHOD: A comprehensive literature
      review. RESULTS: Evidence to support the use of pharmacologic interventions to
      manage psychotic symptoms in elderly patients afflicted with primary psychotic
      disorders and affective disorders is limited by the absence of randomized,
      placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by
      RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the
      treatment of psychotic symptoms has been demonstrated by large RCTs in
      Alzheimer's disease. CONCLUSION: There is evidence of the efficacy of
      antipsychotic medications to manage psychotic symptoms in elderly patients.
      However, the absence of published evidence from RCTs in primary psychotic and
      affective disorders, and the limited evidence in the neurodegenerative illnesses,
      is notable.

PMID- 14653430
TI  - Nonpharmacologic interventions for psychotic symptoms in dementia.
AB  - This article proposes an initial nomenclature and systematic approach for the
      nonpharmacologic understanding and treatment of psychotic symptoms in dementia.
      An analysis of delusions and hallucinations must examine alternative etiologies,
      including misdiagnosis and misunderstanding, the misinterpretation of reality
      because of cognitive losses, sensory deprivation and vision loss, ambiguous
      sensations, and delirium and medical causes. Nonpharmacologic treatments
      frequently follow directly from etiology, such as improving sensory function via
      hearing aids or eyeglasses, providing stimulation, changing antecedents prone to
      misinterpretation (eg, reflections in windows), or circumventing
      misinterpretations (eg, ensuring that an equivalent object is available so there
      is no sense of loss or theft). Given the differences between psychotic symptoms
      in Alzheimer's disease and those in other diseases, the term psychosis should be
      abandoned for most dementia patients, and assessments of etiology should be
      developed. Future research should clarify what proportion of symptoms currently
      identified as psychotic are attributable to related etiologies.

PMID- 14653431
TI  - Cultural aspects of psychosis in the elderly.
AB  - The elderly population is rapidly growing and increasing in diversity.
      Furthermore, mental disorders are common in this population. Elderly patients are
      at increased risk for developing psychotic symptoms. Consequently, clinicians
      must increase their awareness of culture and its effect on psychosis in the
      elderly. This article briefly reviews the components of cultural assessments,
      cultural issues pertaining to diagnosis and treatment, and culture-bound
      syndromes. Some studies have demonstrated ethnic differences in the presention,
      assessment, diagnosis, and treatment of psychotic disorders in the elderly. These
      differences may be explained by factors including clinicians' bias, cultural
      distance between patients and clinicians, culturally biased diagnostic
      instruments, stereotypes of psychopathology, and biological and other
      environmental factors. However, some studies have not documented ethnic
      differences in diagnosing and treating psychotic disorders. Appropriate
      assessments and diagnoses include patients' and clinicians' ethnic and cultural
      contexts. Rigorous methodological research is needed to further evaluate the
      prevalence and treatment of psychotic disorders in ethnic minority elders.

PMID- 14653432
TI  - Erotomania variants in dementia.
AB  - Erotomania is a delusional syndrome in which an affected individual is convinced
      that another person loves him or her. Erotomania usually occurs in middle-aged
      female patients. Only 3 cases have been described in dementia so far. The authors
      report 2 cases, in Alzheimer's disease and vascular dementia, in which erotomania
      emerged in the early stage of the underlying disorder. In both cases, erotomania
      partially responded to antipsychotic treatment. Erotomania may be understood in
      evolutionary terms as a pathologic deviation of an evolved psychological
      mechanism relating to mate selection and may therefore account for the typical
      sex distribution of the syndrome in favor of women and the onset of the disorder,
      usually during the late reproductive phase. The association of erotomania with
      dementing disorders may tentatively be interpreted to suggest that such complex
      psychological mechanisms and behaviors as involved here in "organic" delusions
      may have distinct, "hard-wired" representations in the human brain.

PMID- 14653433
TI  - alpha1-acid glycoprotein in late-life depression: relationship to medical burden
      and genetics.
AB  - Serum alphal-acid glycoprotein (AAG) concentrations were examined in relationship
      to age, medical burden, depression, and mental status in elderly control (n = 19,
      mean age = 72.1 +/- 6.8 years) and depressed (n = 58, mean age = 71.9 +/- 7.1
      years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in
      both groups. Depressed subjects' AAG serum levels were measured at baseline and
      after 6 weeks of antidepressant treatment. Before treatment, depressed subjects
      had significantly higher serum AAG concentrations than nondepressed controls
      (t49.2 = -3.48, P = .0011). Pretreatment AAG levels also correlated with degree
      of medical burden, measured by the Cumulative Illness Rating Scale-Geriatrics (r
      = 0.28, P = .0303), but not with age, depression severity, or cognitive scores.
      There was no significant difference between responders and nonresponders on
      changes in AAG levels from baseline to week 6. Frequency differences in ORM1
      allelic variants apparently did not influence increased AAG concentrations in
      depressed patients.

PMID- 14653434
TI  - Neuroimaging correlates of dementia rating scale performance at baseline and 12
      month follow-up among patients with vascular dementia.
AB  - The authors previously reported that subcortical hyperintensity (SH) and whole
      brain volume (WBV) each covary with different subscale scores of the Mattis
      Dementia Rating Scale (MDRS) among vascular dementia (VaD) patients. The present
      longitudinal analysis examined these relationships for change. The authors found
      that SH volume increased and WBV decreased significantly over 12 months. At
      baseline, SH volume accounted for significant variance in MDRS total score and
      every subscale score, except Memory. WBV was unrelated to any MDRS measure. After
      12 months, SH volume was related only to the Construction subscale score, whereas
      WBV accounted for the majority of variance in Attention and Memory subscale
      performance. These findings indicate that although SH volume increases with
      disease progression, the relative impact of SH volume on cognitive status
      decreases among patients with advanced VaD.

PMID- 14653435
TI  - Can alzheimer's disease and dementias with Lewy bodies be distinguished
      clinically?
AB  - To determine if Alzheimer's disease (AD), its Lewy body (LB) variant (LBV), and
      diffuse LB disease (DLBD) are distinguishable at initial clinical evaluation,
      data from autopsy-confirmed AD, LBV, and DLBD were examined. No significant
      differences were found in age at onset, age at death, total duration of illness,
      duration of illness before initial visit, duration of illness from initial visit
      to death, or severity of illness at initial evaluation. Hallucinations and
      delusions were significantly more frequent for LBV and DLBD, respectively, than
      for AD, and falls were more frequent for DLBD than for AD. Extrapyramidal
      symptoms (EPS) were less frequent in neuroleptic-free AD subjects than in LB
      subjects; the percentage of AD patients with EPS after neuroleptic exposure was
      less than that among LB patients. Seizures were significantly more common for
      DLBD than for AD or LBV. LB dementias differed from AD at initial evaluation,
      with more frequent hallucinations and delusions, EPSs, and seizures, and
      longitudinally in neuroleptic sensitivity, but the data did not distinguish LBV
      from DLBD.

PMID- 14653436
TI  - Are the current guidelines for the acceptance of generic low molecular weight
      heparins adequate?

PMID- 14653437
TI  - Influence of different anticoagulant agents on fibrinopeptide a generation.
AB  - The purpose of this study was to determine the in vitro effects of different
      anticoagulant drugs on fibrinopeptide A (FPA) generation inhibition and to
      identify whether there is any correlation between FPA generation, Hemochron ACT,
      global clotting assays, and chromogenic assays. Unfractionated heparin is a
      conventionally used anticoagulant. New anticoagulant drugs such as low molecular
      weight heparins (LMWHs), pentasaccharide, and antithrombin drugs are now approved
      for various indications. Anti-Xa drugs are in various phases of clinical
      development. The influence of different anticoagulant agents has been studied on
      fibrinopeptide A generation, Hemochron celite ACT, global clotting assays, and
      chromogenic anti-Xa and anti-IIa assays. Different LMWHs (Clivarin, Dalteparin,
      Enoxaparin, and Tinzaparin), anti-Xa agents (Pentasaccharide, DX-9065a and
      unfractionated heparin), and anti-IIa agents (PEG-Hirudin, Hirudin, Efegatran and
      Argatroban) were studied. The blood from healthy volunteers (n=4) was drawn for
      each drug. Imuclone FPA enzyme-linked immunosorbent kit assay, Hemochron celite
      ACT assay, global clotting assays (PT, APTT, Heptest-HI, thrombin time), and
      Loyola chromogenic anti-Xa and anti-IIIa assays were studied. Pentasaccharide
      demonstrated minimal effects on the whole blood clotting time such as ACT and on
      inhibition of FPA generation (IC50 > 25 microg/mL). DX-9065a exhibited a
      significant prolongation of ACT and marked inhibition of FPA generation (IC50 =
      4.12 microg/mL). Unfractionated heparin showed a marked inhibition of FPA
      generation (IC50 = 5.16 microg/mL). Pentasaccharide, DX-9065a and UFH showed a
      marked correlation between ACT and inhibition of FPA generation. LMWHs
      demonstrated concentration-dependent inhibition of FPA generation. LMWHs studied
      showed good correlation between FPA generation inhibition and ACT test. Similar
      correlation was seen between FPA generation inhibition and the APTT, anti Xa
      (heptest-HI assay) and anti-IIa activity. Anti-IIa drugs demonstrated
      concentration-dependent inhibition of FPA generation. Their FPA generation
      inhibition potency is correlated with the ACT assay. A strong correlation between
      Hemochron ACT and FPA generation inhibition was observed. Based on this
      significant correlation, the FPA generation inhibition can be predicted by point
      of-care ACT assay.

PMID- 14653438
TI  - Generic forms of low-molecular-weight heparins: some practical considerations.
AB  - This commentary briefly reviews the controversies of therapeutic and generic
      interchangeability, as they apply to the antithrombotic drug class called low
      molecular-weight heparin (LMWH). Recommendations are prepared for the generic
      LMWH approval process by various regulatory bodies.

PMID- 14653439
TI  - The PAI-1 gene 4G/5G polymorphism and deep vein thrombosis in patients with
      inherited thrombophilia.
AB  - Genetic and acquired factors may influence phenotypic expression of inherited
      thrombophilia. Hypofibrinolysis due to excess PAI-1 can be found in patients with
      deep vein thrombosis (DVT) and 4G/5G polymorphism of the PAI-1 gene may modulate
      the inhibitor's synthesis. In 149 patients with inherited thrombophilia, the
      possible thrombotic contribution of both 4G/5G polymorphism and PAI-1 plasma
      levels was evaluated. Sixty-seven patients with idiopathic DVT and 98 normal
      subjects were also studied. By comparison with controls, a significantly higher
      prevalence of 4G/4G genotype was seen in idiopathic DVT and in thrombophilia
      patients, although in this latter group the difference only remained significant
      in cases symptomatic for thrombosis (p = 0.01). The 4G/4G genotype was associated
      with a greater risk of thrombosis both in symptomatic thrombophilia patients (OR
      2.85, 95% CI 1.26-6.46) and in idiopathic DVT patients (OR 3.1, 95% CI 1.26
      7.59). The greater frequency of 4G allele in symptomatic thrombophilia patients
      with respect to controls was statistically significant (p = 0.04). Compared to
      healthy subjects, PAI-1:Ag levels were higher in symptomatic thrombophilia
      patients and related to the 4G/5G polymorphism, with significantly higher values
      in the 4G/4G carriers. In conclusion, PAI-1 4G/5G polymorphism may influence PAI
      1 expression and thrombotic risk in patients with inherited thrombophilia.

PMID- 14653440
TI  - P-selectin and platelet-derived microparticles associated with monocyte
      activation markers in patients with pulmonary embolism.
AB  - Platelet activation markers (platelet-derived microparticles and P-selectin on
      activated platelets), chemokines (monocyte chemotactic peptide and regulated on
      activation normally T-cell expressed and secreted), and soluble markers (sP
      selectin, sE-selectin, sVCAM-1, and sCD14) were measured and compared in patients
      with pulmonary embolism (PE). These substances are thought to participate in the
      pathogenesis of PE. Levels of all of the platelet activation markers, chemokines,
      and soluble markers were higher in the patients with PE than in normal controls.
      Levels of platelet activation markers were also significantly increased
      postoperatively after total knee arthroplasty. Anti-platelet therapy
      significantly inhibited the elevation of platelet activation markers after total
      knee arthroplasty. These findings suggest that antiplatelet therapy may be useful
      for PE-related interaction of platelets, leukocytes, and endothelial cells.

PMID- 14653441
TI  - Differential effects of DX-9065a, argatroban, and synthetic pentasaccharide on
      tissue thromboplastin inhibition test and dilute Russell's viper venom test.
AB  - New synthetic direct and indirect factor Xa or factor IIa inhibitors are
      increasingly used for the prevention and treatment of thrombotic disorders,
      including patients suffering from antiphospholipid syndrome. In this study, the
      effects of the synthetic direct factor Xa inhibitor DX-9065a, the indirect
      synthetic heparinomimetic pentasaccharide, and the direct factor IIa inhibitor
      Argatroban were studied. These two widely used assays for the detection of lupus
      anticoagulant, namely the tissue thromboplastin inhibition (TTIT) and the dilute
      Russell viper venom tests (DRWT) proved useful. The drugs were added to a normal
      human plasma pool ranging in concentration from 0.04 to 10 microg/mL. Using the
      two tests named above, DX-9065a and Argatroban showed a dose-related prolongation
      of TTIT and DRWT in the concentration range from 0.04 to 5 micromol/mL, but the
      pentasaccharide only slightly prolonged the clotting times of these assays even
      at high concentrations. Argatroban had the more pronounced effect on both tests
      when compared with DX-9065a (p < 0.001). The most responsive assay for DX-9065a
      up to a concentration of 2.5 micromol/mL was the DRWT. For Argatroban both TTIT
      and DRWT were equally responsive. Patients whose plasma was tested for suspected
      lupus anticoagulant and who have been given DX-9065a or Argatroban may have false
      positive results with the TTIT tests and DRWT. This effect should be considered
      during patient management. These results indicate that these assays could be used
      for the effective quantitation of the direct factor Xa or factor IIa inhibitors
      when suitable controls are used.

PMID- 14653442
TI  - Acquired protein C and protein S deficiency in HIV-infected patients.
AB  - Infection with human immunodeficiency virus (HIV) may lead to hemostatic
      imbalances. Forty-nine consecutive patients with acute opportunistic infections
      were screened for thrombophilic parameters. A follow-up investigation was
      performed after 10 +/- 8 weeks in 26 patients. In acutely ill patients, the
      incidence of protein S deficiency was 67% (33/49) and of protein C deficiency 25%
      (12/49), while at the follow-up visit the incidences were 54% (14/26) and 8%
      (2/26), respectively. Protein S and protein C levels increased significantly from
      initial to follow-up visit (p < 0.05). Lupus anticoagulants were not detected and
      anticardiolipin IgG antibodies were present in 11.4% (5/44). Three patients
      presented with deep venous thrombosis on admission; in two, protein S or protein
      C deficiency was observed. In conclusion, an acquired protein S and protein C
      deficiency often develop in patients with HIV and acute illness; this may be
      reversible after treatment for opportunistic infections.

PMID- 14653443
TI  - PCR-RFLP detection of PAI-2 variants in myocardial infarction.
AB  - PAI-2 is one of the regulators of the fibrinolytic system. The importance of the
      fibrinolytic cascades in the pathogenesis of myocardial infarction has been
      demonstrated by many investigators. Recently, some investigators have shown that
      two variants of PAI-2, designated A and B, are associated with the formation of
      large molecular PAI-2 complexes. This polymorphism is therefore present a genetic
      predisposition for the development of coronary artery disease and multiple
      sclerosis. Therefore, the prevalence of this polymorphism among 45 patients with
      MI and 20 control subjects was investigated. The AA genotype of the PAI-2 gene
      was found to be more frequent among those subjects with MI. These data provide
      evidence that a polymorphism of the PAI-2 gene is associated with an increased
      risk of MI.

PMID- 14653444
TI  - A trend of platelet indices in patients with green pit viper toxin.
AB  - The green pit viper (Trimeresurus albolabris and Trimeresurus macrops) is a
      common venomous snake in Thailand. The green pit viper venom has major effects on
      the hematologic system. The venom is found to have a thrombin-like effect in
      vitro but cause a defibrination syndrome in vivo. Unlike other pit viper snakes
      (such as Malayan pit viper and Russel's pit viper), the venomous effect on red
      blood cells is rarely mentioned. Clinical features of venomous snake bites vary
      from asymptomatic to fatal bleeding. In this study, an attempt was made to
      discern hematologic parameters in green pit viper envenomation and to
      characterize the changes in blood cells. The study included data from 40 patients
      who were hospitalized at the King Chulalongkorn Memorial Hospital during 1995 to
      1999 and 40 normal, healthy subjects as control. Concerning platelet
      determination, significantly decreased (p < 0.05) total platelet count and mean
      platelet volume (MPV) were demonstrated in envenomous blood. The changes in blood
      cells may be partly due to the effect of green pit viper toxin on the platelet
      morphology. However, the explanation of this phenomenon requires further
      investigation for the specific pathophysiology. The components of green pit viper
      venom that have these hematologic effects in humans are interesting and should be
      further identified.

PMID- 14653445
TI  - Acute myocardial infarction caused by delayed heparin-induced thrombocytopenia
      and acute immunoreaction due to re-exposure to heparin in a systemic lupus
      erythematosus patient with HIT antibodies.
AB  - A patient with systemic lupus erythematosus and anticardiolipin antibodies and
      antibodies to platelet factor 4/heparin complexes suffered an acute myocardial
      infarction caused by delayed heparin-induced thrombocytopenia after heparin
      administration given to treat pulmonary hypertension. Furthermore, additional
      heparin administration for emergency coronary angiography appeared to have led to
      an acute immunoreaction, which might have resulted in acute coronary occlusion
      during coronary angiography and to a decreased platelet count. The present
      findings suggest that one must suspect delayed-type HIT in rare cases of
      induction of thrombosis after the cessation of heparin treatment, and avoid re
      exposure to heparin in such cases.

PMID- 14653446
TI  - Congenital absence of the inferior vena cava and genetic coagulation
      abnormalities: a rare associated risk factor for recurrent idiopathic deep vein
      thrombosis.
AB  - Congenital absence of the inferior vena cava (AIVC) has been reported as a risk
      factor of deep vein thrombosis (DVT) in young people. DVT is caused by an
      interaction between congenital coagulation abnormalities and acquired risk
      factors. We observed an 18-year-old patient with AIVC who developed recurrent
      deep vein thrombosis at the left leg. Molecular studies showed an etherozigousity
      for FV Leiden gene (G1691A) and a homozigousity for methylenetetraidrofolate
      reductase gene (C677T) in absence of folate and vitamin B12 deficiency. After the
      second DVT episode, the patient has been treated with heparin and oral
      anticoagulant without discontinuation.

PMID- 14653447
TI  - Increased soluble thrombomodulin in hemodialysis patients with long-term
      erythropoietin treatment: what does it reflect?

PMID- 14653448
TI  - Membrane fluidity of blood cells.
AB  - Plasma membranes are fluid structures and the maintenance of fluidity is a
      prerequisite for function, viability, growth and reproduction of cells. Membrane
      fluidity is the reciprocal of membrane microviscosity, which in turn is inversely
      proportional to rotational and lateral diffusion rates of membrane components. In
      the absence of constraints most lipids and unrestrained integral proteins freely
      diffuse in the plane of the membrane with high diffusion coefficients. The fluid
      mosaic model of plasma membrane structure is essentially still valid but this
      model is by its nature a macroscopic one. At present, attention is focused on
      molecular structural details of protein-lipid interactions and on the static and
      dynamic structure of membrane proteins. Highly potent new macroscopic and
      microscopic methods have been developed to measure translational diffusion of
      membrane lipids and proteins. The microscopic methods can reveal diffusion via
      encounters between labeled molecules. Fluorescence anisotropy measurements are
      the most widely used techniques in biological research. The use of different
      permeant and non-permeant fluorophores have contributed much to a better
      understanding of the changes in the ordered states and motional freedom of the
      membrane phospholipids in different cells during development, aging and
      physiological functions as well as in pathological conditions. The application of
      fluorophores with non-random distribution have shed light on the asymmetrical
      changes between the outer and inner domain of the lipid bilayer and on the
      dynamics of 'flip-flop' in signal transduction. Membrane fluidity was shown to
      have a decisive role in the efficiency of ligand binding, in the outcome of
      direct cell to cell contacts and in the modulation of the activity of membrane
      enzymes. Cell filtrability reflects whole cell viscosity that can not always be
      correlated with the fine changes in membrane fluidity. Cell viscosity depends
      inter alia on the size and shape of the cells as well as on membrane rigidity. In
      contrast to this, membrane fluidity is only dependent on the freedom of mobility
      of the membrane constituents. Increased release of free radicals and reactive
      oxygen specie (ROS) affect membrane fluidity, cellular Ca2+ homeostasis, induce
      lipid peroxidation and finally cell death. Investigation of membrane fluidity
      proved to be a useful and sensitive additional method to obtain a better insight
      into the mechanisms by which different compounds, drugs and contact with foreign
      surfaces are affecting cellular functions. The measurements of membrane fluidity
      may gain more widespread use for monitoring the safety and efficacy of these
      actions. During the last few years, changes in membrane fluidity of blood cells
      have been reported during development and aging and as a result of physiological
      cell functions. Membrane fluidity changes have been described in
      thrombocythaemia, hyperlipidaemia, hypercholesterolaemia, hypertension, diabetes
      mellitus, obesity, septic conditions and in allergic and burnt patients, in
      alcoholics, in Alzheimer's disease and in schizophrenia. A short summary is given
      on red cell membrane fluidity changes in a Hungarian triosephosphate isomerase
      (TPI)-deficient family, reflecting how the very subtle changes in membrane
      fluidity can help to establish underlying biological differences between the
      clinical phenotypes of a severe enzyme (TPI) deficiency caused by the defect of a
      single gene in two brothers one with and one without neurological symptoms.

PMID- 14653449
TI  - Primary thyroid non-Hodgkin's lymphomas: clinicopathological observations on
      patients living in the island of Crete.
AB  - Fifteen patients with primary thyroid non-Hodgkin's lymphomas (PT-NHLs) living in
      the island of Crete were studied. Patients' median age was 69 years, male/female
      ratio 1.5/1 and stage I/stage II ratio 2/1 (stages III and IV were excluded).
      According to the Working Formulation Classification, 2 cases were with low, 10
      with intermediate and 3 with high grade of malignancy. Remission rate was 80%,
      median overall survival 61 months and median disease free survival 59 months. No
      significant difference in survival were found between stage I and II, as well as
      between males and females. Conclusing, PT-NHLs in the island of Crete are more
      frequent in males than in females, and are predominantly (67%) of the
      intermediate grade of malignancy.

PMID- 14653450
TI  - The value of the ultrastructural pattern of myeloperoxidase and platelet
      peroxidase in identification of two blastic cell types during transformation of a
      chronic myeloproliferative disorder.
AB  - The value of the ultrastructural pattern of myeloperoxidase (MPO) and
      plateletperoxidase (PPO) staining is evaluated for the identification of the type
      of blastic cells during the acute transformation of a chronic myeloproliferative
      disorder. MPO and PPO are generally accepted as lineage specific markers for the
      detection of myeloid or megakaryocytic differentiation of the blast cells. The
      ultrastructural pattern of myeloperoxidase (MPO) and plateletperoxidase (PPO)
      permitted us to identify two types of blastic cells (one from the myeloid and the
      other from the megakaryoblastic lineage) in the acute transformation of a chronic
      myeloproliferative disorders.

PMID- 14653451
TI  - beta-Thalassaemia and factors affecting the metabolism of lipids and
      lipoproteins.
AB  - Total cholesterol, triglycerides (TG), LDL-cholesterol, HDL-cholesterol, alpha
      lipoprotein (LP) (HDL-LP), pre-beta-LP (VLDL-LP) and beta-lipoprotein (LDL-LP)
      were measured in the blood of 104 patients with major and intermedia form of beta
      thalassaemia and 112 control subjects, mean age +/- SD 10.2 +/- 3.5 and 9.1 +/-
      3.8 years, respectively. Cholesterol, LDL- and HDL-cholesterol were significantly
      decreased and TG was significantly increased in the patients compared to the
      control subjects. TG values in male patients were significantly higher than in
      male control subjects, but no differences were found in females. Patients with
      major and intermedia forms of beta-thalassaemia and chronic hepatitis C have
      significantly lower values of cholesterol and beta-LP and higher values of HDL
      cholesterol than patients without hepatitis C. An increase of HDL-cholesterol and
      alpha-LP was found in patients with diabetes mellitus or impaired glucose
      tolerance (IGT) compared to patients without IGT. In the thalassaemic patients
      there was an increase of TG and pre-beta-LP and a decrease of HDL-cholesterol and
      alpha-LP with increasing ferritin values. There was a positive correlation of the
      patients' age with TG and pre-beta-LP whereas no such correlation was found in
      the control subjects. It appears, therefore, that many factors as iron overload,
      liver injury, hormonal disturbances and aging affects lipids and LP pattern in
      patients with major and intermedia form of beta-thalassaemia.

PMID- 14653452
TI  - Acute megakaryoblastic leukaemia with mediastinal tumor.
AB  - Acute megakaryoblastic leukemia (AMKL) is a rare myeloproliferative syndrome with
      a fulminant clinical course characterized by progressive pancytopenia, pallor,
      weakness and severe hemorrhage. We present a 18-year old male with pancytopenia
      and massive hemorrhage, lymphadenopathy, organomegaly, and with unusual
      presentation of retrocardial mediastinal tumor on the right side. The diagnosis
      of AMKL was established by combining cytological and immunocytochemical analyses
      of peripheral blood cells (blasts were GPIIIa and GPIb positive); by
      immunohistochemical analysis of lymph node (dysplastic megakaryocytes were GPIIIa
      and F VIII positive); in vitro culture studies confirmed enormous growth of CFU
      Mk with high proliferative capacity. In spite of therapy, the patient died 3
      months after the first signs of the disease.

PMID- 14653453
TI  - Lectin binding in the choroid plexuses of the chick embryo.
AB  - In the present research we have studied the distribution and the changes of the
      oligosaccharidic component of the glycoconjugates during the development of the
      choroids plexuses of the 3rd ventricle and of the lateral ventricles in chick
      embryos and in 3-day-old chicken. For this purpose a battery of seven horseradish
      peroxidase labelled lectins was used. Lectin histochemistry has shown that
      starting from early stages of choroid plexuses development, all its components,
      epithelial cells, mesenchyme and endothelial cells of the capillary vessels, show
      lectin reactivity. In the present paper the possible role played by the sugar
      residues of the glycoconjugates in the apical portion and in the cytoplasm of the
      choroid epithelial cells and in the basement membrane is discussed.

PMID- 14653454
TI  - Physical activity, heart and ageing: a morpho-functional study by Echo-Color
      Doppler in sedentary and non sedentary healthy subjects.
AB  - Several papers have shown that in young people sports activity is associated with
      a higher prevalence of cardiac valves incompetence, that can be detected, though
      to a lesser extent, even in healthy subjects randomly selected from the
      population. Aim of the present study was to analyse the effects of physical
      activity not only in young subjects but even in the elderly, with particular
      reference to valve competence, by using the Echo-Color-Doppler. The study cohort
      was represented by 80 healthy young subjects, 40 men and 40 women, aged between
      20 and 25 years, each group subdivided into two subgroups, sedentary and non
      sedentary, and 80 healthy elderly subjects, 40 men and 40 women, aged between 65
      and 91 years, again divided into sedentary and non sedentary. Valve incompetence
      was more frequent in the elderly if compared to young subjects (P<0.001) and in
      non sedentary if compared to sedentary subjects (P<0.01), while no significant
      difference was found between males and females. Worth of interest the fact that
      in young subjects valve incompetence was more frequent in non sedentary if
      compared to sedentary subjects (P<0.001), while in the elderly no significant
      difference was found between sedentary and non sedentary subjects. This original
      datum may be explained both by the natural higher prevalence of valve
      incompetence in the elderly, and by the kind of physical activity usually
      performed by the elderly, i.e. endurance activity.

PMID- 14653455
TI  - Abstracts of the 4th Meeting of the Italian Association of Veterinary
      Morphologists. Torino-Grugliasco, 29-31 May 2003.

PMID- 14653459
TI  - Identification of quantitative trait loci for receiving pecks in young and adult
      laying hens.
AB  - Feather pecking (FP) is a major problem in cage and free-range housing systems.
      In free-range systems, FP is more difficult to control. It is not known why a
      victim is being pecked. It could be that a bird is genetically predisposed to be
      pecked. To study the genetics of FP behavior, a large F2 population of 630 hens
      was generated from a cross between two commercial laying lines differing in their
      propensity to feather peck. The traits measured at 6 and 30 wk of age were
      receiving gentle FP, receiving severe FP, and receiving aggressive pecking. In
      addition, receiving toe pecking (TP) was also measured at 30 wk of age. For
      receiving gentle FP at 6 wk of age, a significant QTL on GGA1 and three different
      suggestive QTL were identified on GGA2, GGA6, and GGA7, respectively. For
      receiving gentle FP at 30 wk of age, a suggestive QTL on GGA5 was detected. For
      receiving aggressive pecking, a suggestive QTL was detected on GGA3. For
      receiving TP, three suggestive QTL were detected on GGA1, GGA5, and GGA23,
      respectively. The different QTL detected for receiving gentle FP at different
      ages indicate that this trait is regulated by different genes in young and adult
      hens.

PMID- 14653460
TI  - Effects of whole wheat feeding on the development of coccidial infection in
      broiler chickens.
AB  - A complete ground and pelleted feed was compared to free choice feeding of whole
      wheat and a pelleted protein concentrate during three experimental infections
      with coccidia in broiler chickens. At 22 d of age birds were inoculated with
      different doses of sporulated oocysts of a cecal species (Eimeria tenella) in
      experiment 1 or intestinal species E. maxima or E. acervulina in experiments 2
      and 3, respectively. The effects of diets were assessed on weight gain,
      hematocrit (during cecal coccidiosis), serum coloration (during intestinal
      coccidiosis), oocyst excretion, and lesion score until 7 d post-inoculation. In
      experiment 1 before inoculation, the birds fed whole grain had more beneficial
      microflora with lower counts of coliform bacteria. As shown by oocyst output and
      lesion score, whole wheat feeding increased parasite development during infection
      with the cecal parasite E. tenella. This led to significantly lower weight gain
      with whole wheat than with ground wheat from 5 to 6 d post-inoculation and to
      lower hematocrit at the highest infective dose. Parasite development in
      experiments 2 and 3 was similar among diets, during intestinal infection with E.
      maxima and E. acervulina, respectively, with no significant differences in lesion
      score. During the acute phase (4 to 7 and 3 to 5 d post-inoculation), when a
      difference appeared between diets, whole wheat fed-birds were always more
      affected than ground diet-fed birds in terms of serum coloration and weight gain.
      These results might be explained by modifications of digestive physiology and
      intestinal microflora by whole wheat.

PMID- 14653461
TI  - Quantification and control of the spatiotemporal gradients of air speed and air
      temperature in an incubator.
AB  - Around the optimal incubator air temperature only small spatiotemporal deviations
      are allowed. However, air speed and air temperature are not uniformly distributed
      in the total volume of the incubator due to obstruction of the eggs and egg
      trays. The objectives of this research were (1) to quantify the spatiotemporal
      gradients in temperature and velocity and (2) to develop and validate a control
      algorithm to increase the uniformity in temperature during the entire incubation
      process. To improve the uniformity of air temperature, the airflow pattern and
      the air quality need to be controlled more optimally. These data show that the
      air temperature between the eggs at a certain position in a large incubator is
      the result of (1) the mean air temperature of the incubator; (2) the exchange of
      heat between the egg and its micro-environment, which is affected by the air
      speed at that certain position; (3) the time-variable heat production of the
      embryo; and (4) the heat influx or efflux as a result from the movement of hot or
      cold air in the incubator toward that position, which is affected by the airflow
      pattern. This implies that the airflow pattern needs to be controlled in a more
      optimal way. To maximize the uniformity of air temperature, an active and
      adaptive control of the three-dimensional (3-D) airflow pattern has been
      developed and tested. It was found to improve the spatiotemporal temperature
      distribution. The chance of having a temperature reading in the interval from
      37.5 to 38.1 degrees C increased by 3% compared to normal operating conditions.

PMID- 14653462
TI  - Effect of storage condition on bone breaking strength and bone ash in laying hens
      at different stages in production cycles.
AB  - This study was conducted to determine the effects of refrigeration and frozen
      storage on tibia breaking strength (kg/g) and tibia ash (%) in bones obtained
      from hens of different ages. A total of 75 Single Comb White Leghorn hens were
      divided into three equal groups according to age (72, 80, and 92 wk of age). Both
      tibias of each hen were harvested and immediately defleshed. The tibias from each
      hen were randomly assigned to either 1 d of refrigeration or 7 d of frozen
      storage. Tibia breaking strengths were determined using an Instron Universal
      Testing Machine with 50-kg-load cell at 50-kg-load range with a crosshead speed
      of 50 mm/min. Tibia ash weights were determined by ashing for 24 h at 615 degrees
      C. Bone breaking strength in 72 wk of age hens was significantly (P < 0.05)
      higher in refrigerated tibias (2.48 kg/g) than those in frozen storage (1.75
      kg/g). However, there was no difference (P > 0.05) for bone ash (percentage of
      tibia ash) in all three groups between refrigerated storage (72 wk: 38.840%, 80
      wk: 46.40%, 92 wk: 46.99%) and frozen storage (72 wk: 39.12%, 80 wk: 44.88%, 92
      wk: 45.35%). This study indicated that frozen storage only influenced assessment
      of bone strength in 72-wk-old laying hens but could be used for sample storage of
      bones from older hens.

PMID- 14653464
TI  - Immunization of broiler chicks by in ovo injection of Eimeria tenella
      sporozoites, sporocysts, or oocysts.
AB  - Immunization of chickens by in ovo injection of Eimeria tenella parasite stages
      was investigated. Fertile Hubbard x Petersen broiler chicken eggs were injected
      through the air cell on d 18 of incubation with sporozoites, sporocysts, or
      oocysts of E. tenella. Injected doses were in the range of 1 x 10(2) to 1 x 10(6)
      sporozoites, 2 x 10(5) to 2 x 10(7) sporocysts, or 1 x 10(2) to 5 x 10(6) oocysts
      per egg. Hatch rates were generally unaffected. Hatched chicks shed oocysts, with
      oocysts per gram of feces reaching a maximum at 3 d posthatch for chicks injected
      with sporozoites and at 7 d posthatch for chicks receiving oocysts or sporocysts
      in ovo. After 2 wk in wire-floored cages or 3 wk on litter, birds were challenged
      with 2.5 x 10(4) sporulated oocysts of E. tenella. Chicks immunized by in ovo
      injection of parasite stages had significantly reduced lesion scores compared to
      their nonimmunized counterparts. The results demonstrate the feasibility of
      immunizing broiler chickens against E. tenella infection by in ovo injection of
      sporozoites, sporocysts, or oocysts.

PMID- 14653463
TI  - Effects of cold stress on immune responses and body weight of chicken lines
      divergently selected for antibody responses to sheep red blood cells.
AB  - Effects of cold stress (CS) on the immune system of chicken lines divergently
      selected for high (H line) and low (L line) antibody responses to SRBC next to a
      randombred control (C) line were studied. Three- to four-week-old growing chicks
      of the three lines were feed-restricted at 80% ad libitum and subjected to CS at
      10 degrees C continuously for 7, 5, 3, 1, or 0 d prior to immunization with
      keyhole limpet hemocyanin (KLH). Specific and natural antibodies were measured in
      the three chicken lines subjected to or not subjected to various durations of CS
      prior to immunization. In addition to antibodies we also measured in vitro
      lymphocyte proliferation as a measure of cell-mediated immunity (CMI), zymosan
      induced reactive oxygen intermediates (ROI) production as a measure of
      phagocytosis, and BW gain as a measure of production trait. In general,
      significantly higher antibody responses to KLH and natural antigens were found in
      the H line as compared to the other two lines. Specific antibody responses to KLH
      were not significantly affected by CS, but an acute transient increase in natural
      antibody titers to ovalbumin was found in H line birds subjected to 1 d of CS,
      which was not found in C or L line birds. On the other hand, an acute significant
      increase in natural antibody titers to lipopolysaccharide (LPS) was found in C
      and L line birds subjected to 1 d CS but not in H line birds. Cold stress
      enhanced the ROI production. In addition, 7 d of CS significantly enhanced
      cellular immunity in vitro, but no significant line effects with respect to
      cellular immunity were found. BW gain was negatively affected by CS, especially
      when CS was applied for longer periods. We concluded that birds responded
      immediately to CS with enhanced innate (phagocyte and natural antibody) immunity,
      irrespective of genetic background. When CS is prolonged, the cellular adaptive
      immune response is affected also. Although reallocation of energy was not
      measured, our data suggested that under limited conditions (e.g., restricted
      feeding) with simultaneous stress (e.g., CS), growth and cellular immunity were
      more sensitive than thermoregulation and humoral immunity. With respect to vital
      life traits, thermoregulation may have first priority followed by adaptive
      cellular immunity, humoral immunity, and BW gain. The relationships between
      immune responses and adaptation to stress are discussed.

PMID- 14653465
TI  - Alleles of cytosolic phosphoenolpyruvate carboxykinase (PEPCK): trait association
      and interaction with mitochondrial PEPCK in a strain of White Leghorn chickens.
AB  - White Leghorn chickens from a nonselected closed population were typed for two
      RFLP located in the 3' end of the gene coding for cytosolic phosphoenol-pyruvate
      carboxykinase (PEPCK-C), a major control gene of gluconeogenesis. The two RFLP
      gave rise to three alleles (or haplotype classes), thus defining six genotypes.
      Feed efficiency (FE) and residual feed consumption (RFC) varied significantly
      among the genotypes and indicated that all three haplotypes differed from each
      other. FE is the ratio between feed consumption and egg mass produced, whereas
      RFC is the feed consumption after correcting for BW and egg production. There was
      significant interaction between PEPCK-C genotypes and mitochondrial PEPCK (PEPCK
      M) genotypes defined by a single RFLP. The latter enzyme catalyzes the same
      reaction but is located in the matrix of the mitochondria and is encoded by a
      different nuclear gene. Interaction was evident from an analysis of the egg
      weight and egg specific gravity in the early phase of egg laying. It was such
      that the effect of the variation in one gene depended entirely on the genotype of
      the second gene. In addition, significant genotypic disequilibria were observed
      between two of the three alleles of PEPCK-C and between one of these alleles and
      the two RFLP alleles of PEPCK-M. This finding indicates variations of genes in
      the gluconeogenesis pathway may affect feed utilization and egg production
      traits, as well as reproductive fitness.

PMID- 14653467
TI  - Efficacy of a phytase derived from Escherichia coli and expressed in yeast on
      phosphorus utilization and bone mineralization in turkey poults.
AB  - A slope-response bioassay was conducted with male turkey poults to determine the
      sparing effect of P, based on improvements in bone mineralization in turkey
      poults, from 10 to 21 d of age when diets were supplemented with a novel phytase.
      Reference diets for calculation of the sparing effect of P contained 0.47, 0.55,
      0.70, and 0.79% nonphytate phosphorus (NPP). Diets with varying dosages of a
      swine, Escherichia coli-derived AppA2 phytase (ECP) expressed in Pichia pastoris
      yeast (0, 250, 500, 750, and 1,000 U/kg) were added to the 0.47% NPP diet and
      improvements in bone mineralization determined the sparing effect of P supplied
      from ECP. Two additional reference diets were included that contained 500 U/kg
      from one of two commercial phytases (PA and PB) derived from Aspergillus and
      Peniophora. At 500 U/kg diet the ECP spared an additional 0.22% NPP (if
      calculated from tibia ash %), 0.18% NPP (if calculated from toe ash %), 0.24% NPP
      (if calculated from mg tibia ash), or 0.21% NPP (if calculated from mg toe ash).
      Phosphorus retention results validate bioassay results, in that 500 U ECP/kg
      resulted in 68.2% P being retained (0.49% of diet P retained) as compared with
      only 58.9% P being retained from the unsupplemented control diet (0.421% of diet
      P retained; P < 0.05).

PMID- 14653466
TI  - Effect of enzyme addition on the digestibilities of cell wall polysaccharides and
      oligosaccharides from whole, dehulled, and ethanol-extracted white lupins in
      chickens.
AB  - Three experiments were conducted to examine the effects of a commercial enzyme
      preparation on chicks performance and digestibilities of nonstarch
      polysaccharides (NSP), raffinose (R), stachyose (S), and total oligosaccharides
      (O) in diets containing whole and dehulled lupin and ethanol-extracted dehulled
      lupin meal. Ethanol extract was also used to produce a rich oligosaccharide
      fraction. In the first experiment, the dehulling treatment and the addition of
      enzyme to the diet improved (P < 0.05) weight gain (24 and 15%), feed-to-gain
      ratio (13 and 9%), dry matter retention (32 and 8%), apparent protein
      digestibility (6 and 3%) and ileal digestibilities of raffinose (19 and 119%),
      stachyose (85 and 204%), and total oligosaccharides (68 and 178%), respectively.
      In addition, enzyme treatment improved (P < 0.05) excreta digestibility values
      for NSP (from -1.7 to 5.5%), R (from 64.6 to 92.6%), S (from 48.8 to 82.4%), and
      O (from 55.8 to 83.5%). In the second experiment, extraction of the ethanol
      soluble components from dehulled lupin decreased (P < 0.0001) weight gain (51%),
      and increased (P < 0.0001) feed consumption (34%), feed-to-gain ratio (32%),
      relative gizzard weight (14%), and the relative ceca length (20%). The addition
      of the isolated fraction of oligosacharides to the corn-extracted lupin diet (7.5
      and 15%) yielded performance values similar to those obtained with the
      unextracted dehulled lupin. The addition of enzymes to the diets significantly
      improved the weight gain (11%) and feed to gain ratio (6%), and decreased
      relative gizzard weight (12%) and relative ceca length (7%). Ileal
      digestibilities of R, S, and O were considerably lower than corresponding excreta
      digestibilities. The excreta digestibility of NSP and excreta and ileal
      digestibilities of R, S, and O were lower (P < 0.05) in chicks fed the lupin diet
      containing the high concentration of extract compared with those fed the same
      diet containing the lower concentration of extract. Enzymes, when added to the
      diets, increased (P < 0.05) the digestibilities of R, S, and O with the relative
      effects being much greater for ileal than excreta samples. In the third
      experiment, the ethanol extract (7.5 and 15%) added to a corn-soybean diet
      improved weight gain, feed consumption, and feed-to-gain ratio by 19, 13, and 6%,
      respectively. Ileal digestibilities of R, S, and O were low (< 45%), especially
      in chicks fed the diets containing the high amount of added oligosaccharide
      fraction. There was no effect of enzyme addition on the performance parameters.
      However, supplemental dietary enzymes improved (P < 0.05) ileal and excreta
      digestibilities of oligosaccharides from 15.6 and 68.6% to 52.3 and 84.8%,
      respectively. In summary, dehulling greatly improved the nutritional value of
      lupin, while removal of the ethanol soluble materials, including raffinose and
      stachyose considerably decreased its value. The oligosaccharide fraction does not
      seem to have an antinutritive effect and the addition of enzymes increased the
      digestibilities of NSP, raffinose, and stachyose but did not significantly
      improve chick performance.

PMID- 14653468
TI  - Growth responses to dietary lysine at high and low ambient temperature in male
      turkeys.
AB  - Several researchers have postulated that dietary lysine requirements for turkeys
      are dependent upon ambient temperature. To test and quantify this hypothesis, a
      factorial experiment was designed with four dietary lysine levels (75, 90, 105,
      and 120% of NRC lysine recommendations) from 1 d of age onward and two ambient
      temperatures (15 vs. 30 degrees C) from 4 wk of age onward. Growth performance
      and carcass yields were measured, and requirements were derived from the fitted
      exponential response curves at 95% of the maximum possible response above that of
      the basal diet. In the entire experiment no significant interaction effects
      between temperature and lysine were observed for feed intake, BW gain, and
      feed:gain ratio. Exponential curves gave a very good fit (R2 > 0.89) for feed
      intake, and BW gain responses to dietary lysine concentrations in all age
      intervals. The dietary lysine requirement was estimated to be 1.67 +/- 0.09%,
      1.19 +/- 0.13%, 1.08%, and 0.94 +/- 0.35% from 29 to 56 d, 57 to 84 d, 85 to 114
      d, and 115 to 140 d of age, respectively. High temperature decreased all absolute
      processing yields in kilograms but relative cold carcass yield and relative
      yields of thighs, drums, and wings were increased by high temperature. Relative
      breast meat yield and abdominal fat were decreased by high temperature. Turkeys
      at low temperature responded with more breast meat to high lysine than at high
      temperature.

PMID- 14653469
TI  - Morphological, molecular, and functional changes in the chicken small intestine
      of the late-term embryo.
AB  - The rapid development of the gastrointestinal tract posthatch has been described;
      however, little information exists concerning the development of the small
      intestine in the prehatch period. The present study examined the morphological,
      cellular, and molecular changes occurring in the small intestine toward the end
      of the incubation period by examining the expression of intestinal genes that
      code for brush border digestive enzymes and transporters, their biochemical
      activities, and the morphological changes in the mucosal layer. The results
      indicated that during the last 3 d of incubation the weight of the intestine, as
      a proportion of embryo weight, increased from approximately 1% on d 17 of
      embryonic age to 3.5% at hatch. At this time the villi could be divided into two
      main developmental stages, differing in their length and shape, with the larger
      villi often being pear-shaped and the smaller villi being narrower and having a
      rocket-like shape. However, on d 19 a further stage of villus development was
      observed. Activities of maltase, aminopeptidase, sodium-glucose transporter
      (SGLT)-1, and ATPase began to increase on d 19 and further increased on the day
      of hatch. The expression of mRNA for these brush-border membrane (BBM) enzymes
      and transporters was detected from d 15. Determining quantities relative to beta
      actin indicated that expression of all parameters examined was low on d 15 and
      17, increased 9- to 25-fold on d 19, and all decreased again on the day of hatch.
      Relative expression of mRNA of the different enzymes and transporters were
      correlated as were their activities (r = 0.75 to 0.96); however, expression was
      not correlated with enzymatic activities. The role of these parameters in the
      ontogeny of absorption is discussed. Thus, major changes in the expression and
      localization of the functional brush-border proteins prepare the framework for
      ingestion of carbohydrate- and protein-rich exogenous feed posthatch.

PMID- 14653470
TI  - Dose-response relationships for valine in the growing White Pekin duck.
AB  - The response of White Pekin ducks to supplements of L-valine was studied during 3
      wk posthatching. The basal valine concentration was 6.8 g/kg in a diet containing
      18% CP and 2,990 kcal ME/kg (12.5 MJ ME/ kg). L-valine was supplemented in eight
      graded levels up to 12.7 g/kg at the expense of L-glutamic acid. Three pens of 14
      ducks were allocated to each valine level. Diets were offered ad libitum. Body
      weight gain and feed/gain ratio were studied. At the end of wk 3, ducks were
      killed, processed to a homogenous mass, and analyzed for total body CP and amino
      acid content. Accretion of protein and amino acids was calculated. Additionally,
      a 5-d N balance study was conducted with separate ducks of the same hatch
      beginning on d 11 (6 ducks per treatment). The response of ducks to increasing
      valine concentration was described by exponential functions. Ducks significantly
      responded to the increasing valine concentration in growth, feed/gain ratio, and
      protein accretion. Ninety-five percent of y(max) in BW gain and protein accretion
      were achieved with 8.0 and 7.9 g valine/kg, respectively. The content of protein
      in gained BW was, on average, 149 g/kg without a significant valine effect. The
      valine content in accreted body protein was also unaffected by dietary valine
      (4.1 g/16 g N on average), which suggested that a major shift in body protein
      fractions did not occur. The overall efficiency of valine utilization was
      affected by dietary valine concentration and showed a maximum of 49%. Data from
      the balance study showed basically the same response of ducks, but the estimated
      optimum in dietary valine concentration was lower (7.0 g/kg). A comparison with
      published broiler data indicated that ducks and broilers in this age period were
      similar with regard to the valine content in gained protein and the efficiency of
      utilization of supplemented valine.

PMID- 14653471
TI  - Interrelationship between environmental temperature and dietary nonphytate
      phosphorus in laying hens.
AB  - Four experiments were conducted to evaluate the effects of phosphorus nutrition
      on laying hens exposed to heat stress (HS). Hens were fed their respective diet
      for at least 3 wk prior to initiation of each experiment to allow the hens fed
      low-P diets to become P deficient. In most experiments, hens housed in non-HS
      conditions were pair-fed to the HS hens to maintain equal feed intake. In
      experiments 1 and 2, two levels of nonphytate P (NPP; deficient at 0.10 or 0.16%
      vs. control at 0.45%) and two temperatures (constant thermoneutral at 21 degrees
      C or cyclic HS up to 35 degrees C) were evaluated. Low NPP significantly reduced
      feed intake and hen-day egg production, but the cyclic heat treatment had no
      effect on hen performance. Experiment 3 was similar to experiments 1 and 2 except
      that constant HS was implemented. Both constant HS and low dietary NPP reduced
      feed intake and egg production, and there was no significant interaction between
      HS and dietary NPP level. In experiment 4, hens were fed 0.10 or 0.45% NPP diets
      and exposed to a more severe HS (38 degrees C) for 8 h. Hens fed the deficient
      NPP level showed a 16% incidence of severe heat distress (unable to stand,
      unresponsive). Our results generally indicated that there was no interaction
      between dietary NPP level and HS in laying hens. However, subjecting hens that
      had been fed a P-deficient diet to an acute HS of 38 degrees C did increase the
      incidence of severe heat distress.

PMID- 14653472
TI  - Effectiveness of twenty-five-hydroxycholecalciferol in the prevention of tibial
      dyschondroplasia in Ross cockerels depends on dietary calcium level.
AB  - Five experiments were conducted to evaluate the efficacy of 25
      hydroxycholecalciferol [25-(OH)D3] to minimize the development of tibial
      dyschondroplasia (TD) and improve phytate phosphorus retention in Ross cockerels
      during the starter period. In experiment 1, chicks were fed a TD-inducing (0.67%
      calcium) diet with or without exposure to ultraviolet light and no supplemental
      cholecalciferol. Dietary 25-(OH)D3 was added at 0, 10, or 70 microg/kg for both
      light treatments. In experiment 2, 25-(OH)D3 was added at 0, 10, 40, or 70
      microg/kg to a TD-inducing diet containing 27.5 microg/kg added cholecalciferol.
      Experiment 3 was similar to experiment 2 except a diet marginal (0.85%) in
      calcium was fed, and cholecalciferol was added at 55 microg/kg. In experiments 4
      and 5, 25-(OH)D3 was added at 0, 18, 36, 54, 72, or 90 microg/kg to a diet
      marginal in calcium. Dietary 25-(OH)D3 decreased the incidence of TD similarly at
      40 and 70 microg/kg 25-(OH)D3 and improved phytate phosphorus retention when the
      TD-inducing diet was fed. The incidence of TD was decreased when 70 microg/kg 25
      (OH)D3 was added to a diet marginal in calcium in experiment 3 only. Phytate
      phosphorus retention was generally not affected by dietary 25-(OH)D3 when a diet
      containing marginal calcium, adequate phosphorus, and high cholecalciferol was
      fed. The effectiveness of 25-(OH)D3 to reduce the incidence of TD in young
      broilers was higher when the dietary calcium level was below 0.85%. The incidence
      of TD in Ross cockerels was low (< 25%) when dietary calcium was greater than
      0.85%.

PMID- 14653473
TI  - Heavier chicks at hatch improves marketing body weight by enhancing skeletal
      muscle growth.
AB  - This study examined some of the factors connected with the greater marketing
      weight observed in chicks hatching with higher BW. Examination of chicks hatching
      from maternal flocks of different ages indicated that BW at hatch increased
      quadratically and yolk sac weight linearly with age, whereas components of the
      gastrointestinal tract showed no significant trend. Growth of pectoralis muscles
      and gastrointestinal tract were compared in chicks hatching at the same weight
      from maternal flocks of 28 and 64 wk of age and in chicks from the same maternal
      flock (44 wk old) hatching at different weights. The results indicated that no
      differences were found among chicks hatching with the same weight from maternal
      flocks of different ages. In contrast, in chicks from the same maternal flock
      hatching at different weights the gastrointestinal tract tended to compose a
      smaller proportion of BW in large chicks, and its growth was not correlated with
      performance. Liver proportions were greater in heavier chicks. Pectoralis growth
      and satellite cell numbers and activity were greater in heavier chicks through 5
      d posthatch, and pectoralis muscles were heavier at marketing. Examination of
      some of the growth factors involved suggested that in heavier chicks satellite
      cells underwent higher proliferation and earlier differentiation during their
      critical period of activity in the immediate posthatch days. To determine when
      these differences in activity were established, examination of 15-d embryonic
      myoblast activity indicated that at this stage activity was already greater in
      the heavier eggs. This finding suggests that programming of muscle growth may be
      completed in late embryonic stages. This study suggests that enhanced satellite
      cell activity is involved in increased growth of chicks hatching with higher BW.

PMID- 14653474
TI  - Bone densitometry as an indicator of percentage tibia ash in broiler chicks fed
      varying dietary calcium and phosphorus levels.
AB  - The relative sensitivity of tibia bone mineral content (BMC) and density (BMD),
      percentage ash (ash), and shear force as indicators for dietary Ca and P was
      compared in 3-wk-old broiler chicks. One hundred eight 7-d-old chicks were
      grouped by weight into 6 blocks of 3 cages each with 6 birds per cage. Three corn
      soybean meal-based diets were randomly assigned to cages within each block. The
      diets were low P, medium P, and adequate P and were formulated to contain 4.0,
      5.1, and 7.8 g of total P/kg feed, respectively; and 5.1, 6.7, and 10.0 g of
      Ca/kg feed, respectively. The chicks were fed the experimental diets for 14 d. On
      d 22, chicks were killed, and tibiae were removed from 3 birds/cage. Weight gain,
      feed intake, feed efficiency, BMC, BMD, shear force, and ash were determined. The
      BMC and BMD were determined using dual energy x-ray absorptiometry. Correlations
      among the various bone status variables and dietary Ca and P were determined.
      Growth performance criteria and ash increased linearly, and BMC and BMD increased
      linearly and quadratically as dietary concentrations of Ca and P increased. The
      correlation coefficient between dietary Ca and BMC, BMD, shear force, or ash was
      0.89, 0.91, 0.50, or 0.89, respectively; and between dietary P and BMC, BMD,
      shear force, or ash was 0.88, 0.91, 0.48, or 0.89, respectively. The correlation
      coefficient between ash and BMC, BMD, or shear force was 0.92, 0.93, or 0.67,
      respectively. The correlation coefficients for linear regression between shear
      force and BMC or BMD was 0.56. The regression model for predicting percentage ash
      using BMD was as follows: percentage ash = 24 + (240 x BMD) with an r2 of 86%. It
      is concluded that in broiler chicks, tibia ash, BMC, and BMD may be more
      sensitive than shear force as indicators of dietary Ca and P concentrations and
      that BMD as measured by dual energy x-ray absorptiometry may be used to predict
      percentage of tibia ash.

PMID- 14653475
TI  - 1alpha-hydroxycholecalciferol has little effect on phytate phosphorus utilization
      in laying hen diets.
AB  - Previous research in our laboratory demonstrated marked increases in phytate P
      utilization when P-deficient corn-soybean meal diets were supplemented with 1a
      hydroxycholecalciferol [1alpha-(OH) D3] and fed to chicks. Our objective was to
      determine if 1alpha-(OH) D3 would improve phytate P utilization when supplemented
      to vitamin D-adequate laying hen diets. The five experimental treatments were 1)
      P-deficient corn-soybean basal diet [17% CP, 3.8% Ca, and 0.10% nonphytate NPP)],
      2) basal with 2.5 microg/kg 1alpha-(OH) D3, 3) basal with 5 microg/kg 1alpha-(OH)
      D3, 4) basal with 10 microg/kg 1alpha-(OH) D3, and 5) basal with 0.35%
      supplemental inorganic P (0.45% NPP, positive control). Diets were fed to six
      replicate groups of 12 HyLine W-98 White Leghorn laying hens from 44 to 52 wk of
      age. Hen-day egg production was significantly depressed by 47 wk of age for the
      basal diet treatment and by 47, 49, and 48 wk of age, respectively, for the 2.5,
      5, and 10 microg/kg of 1alpha-(OH) D3 treatments compared to the positive control
      diet. Supplementation with 5 or 10 microg/kg 1alpha-(OH) D3 did improve (P <
      0.05) egg production, but egg production for those treatments was much lower than
      that for the 0.45% NPP treatment. Our results indicate that 1alpha-(OH) D3 did
      not substantially improve P utilization in laying hens fed corn-soybean meal
      diets.

PMID- 14653476
TI  - Attributes of broiler breeder males characterized by low and high sperm mobility.
AB  - The attributes of broiler breeder males characterized by sperm mobility phenotype
      were studied in replicate experiments. Low and high phenotypes were observed in
      the first experiment over a 10-wk interval. Average straight line velocity
      differed between phenotypes (P < or = 0.05) as evidenced by computer-assisted
      sperm motion analysis. The second experiment compared low and high phenotypes
      from the same broiler breeder strain over a 29-wk interval. Body weight and
      fertility were measured in this experiment. Body weight data approximated
      parallel lines. The low phenotype averaged 227 g more than the high phenotype
      over the course of the experiment. Individual males were used as semen donors at
      50, 54, 58, 62, and 65 wk of age. Eggs were collected for 2 wk after a single
      insemination at each age. Mean overall fertility (+/- SEM) was 44 +/- 4 and 69 +/
      2% for low and high sperm mobility phenotypes, respectively (P < or = 0.0001).
      As determined by transmission electron microscopy, the percentage of sperm with
      aberrant mitochondria was greater for the low sperm mobility phenotype (P < or =
      0.0001). Neither blood plasma testosterone concentration nor testis weight
      differed between phenotypes. Sperm mobility is a biologically significant
      predictor of broiler breeder semen quality. The relationship between sperm
      mobility phenotype and body weight warrants further investigation.

PMID- 14653477
TI  - Effect of vitamin E on lipid peroxidation and fertility after artificial
      insemination with liquid-stored turkey semen.
AB  - Turkey sperm plasma membranes contain high levels of polyunsaturated fatty acids
      that are susceptible to lipid peroxidation during in vitro storage at 4 degrees
      C. Herein we assessed the degree of lipid peroxidation and fertility potential of
      semen liquid-stored for 24 h with the antioxidant vitamin E. Semen was collected
      weekly from 44 males and pooled as pairs (total = 22); the individuals in paired
      samples exhibited similar semen quality parameters. After initial semen
      evaluation, pooled samples were extended with Beltsville Poultry Semen Extender
      containing no supplement (control) or 10 or 40 microg/mL vitamin E and then
      stored at 4 degrees C with constant aeration for 24 h. Lipid peroxidation was
      determined by measuring malonaldehyde (MDA) in aliquots (50 x 10(6) sperm) of
      fresh (0 h) and stored (24 h) semen. Sperm mobility was also evaluated. A total
      of 176 hens (8 hens/tom pair; 4 hens/0 h, 4 hens/24 h) were inseminated (150 x
      10(6) sperm) weekly for 6 wk, and fertility was determined after 7 d of
      incubation. Initial MDA values of the 22 tom pairs ranged from 0.928 to 1.36 uM.
      Males varied in production of MDA during in vitro storage, with most pairs
      exhibiting a threefold increase. Results indicated that supplemental vitamin E
      did not reduce lipid peroxidation during liquid storage. Not surprisingly,
      artificial insemination with stored semen (with much higher MDA values) yielded
      lower fertility rates than control regardless of the presence of vitamin E. These
      results demonstrate that lipid peroxidation is a significant factor affecting the
      fertility of stored turkey sperm and that methods to prevent or reduce lipid
      peroxidation remain to be elucidated.

PMID- 14653479
TI  - Effects of electrical stunning frequency and voltage combinations on the presence
      of engorged blood vessels in goose liver.
AB  - The purpose of this study was to investigate the influence of nine electrical
      stunning methods using various frequency and voltage combinations on the
      occurrence of engorged blood vessels in goose liver. Two hundred seventy Gourmaud
      geese (liver-type line SI 14) were slaughtered at 12 wk of age, in groups of 90
      at three different times. Thirty birds each were subjected to one of the nine
      stunning methods. Neck cutting was performed immediately after stunning. The
      duration of exsanguination was 11 min. After completion of bleeding, the birds
      were scalded, defeathered manually, and kept refrigerated. At 1 d postmortem, the
      carcasses were eviscerated and cut up. From the slaughterhouse, the livers
      chilled in ice were transported to the cannery where they were weighed and graded
      at 2 d postmortem and were further processed. All of the veins and capillaries
      full of blood were removed from livers, because their presence was a hazard to
      product quality by causing discoloration of the canned liver, and the percentage
      of liver weight loss was then determined. The loss in liver weight due to removal
      of engorged blood vessels was reduced (P < 0.05) at 350 Hz, 70 to 90 V, and 80 to
      85 mA when compared to the results obtained with any other stunning method
      tested. It was concluded that the use of high-frequency currents for electrical
      stunning of liver geese might have considerable commercial advantages.

PMID- 14653478
TI  - Semen dilution prior to analysis influences the ability of the sperm quality
      analyzer to predict fertility whether inseminating with a constant number of
      sperm or a constant volume of semen.
AB  - Previous research has shown that the sperm quality index (SQI) is positively
      correlated with semen characteristics as well as fertility when broiler breeder
      semen is diluted 10-fold prior to analysis. However, research has not been
      conducted to establish if semen dilution rate affects the ability of the SQI to
      predict fertility when inseminating a constant number of sperm or a constant
      volume of semen. As a result, 3 experiments were undertaken. The objective of the
      first study was to determine if diluent, minimum essential media, or 0.85% saline
      affects the SQI. The second objective was to identify potential semen dilution
      rates for the SQI by obtaining the range in live sperm concentrations to which
      the SQI is most sensitive. The purpose of experiment 3 was to determine which
      semen dilution rate, 10-, 25-, 50-, 75-fold, or a constant concentration of 180 x
      10(6) sperm/mL, yields an SQI that is most predictive of fertility. Once a week
      for 3 wk, 20 hens were individually inseminated with either 20 microL of 4-fold
      diluted semen or a constant 45 x 10(6) sperm from each of 29 broiler breeder
      males. To determine which semen dilution rate yielded an SQI that was most
      predictive of fertility, Pearson's correlation coefficients were obtained between
      the SQI at each dilution rate and fertility. There was no difference in the SQI
      due to diluent. Sperm quality index values declined logarithmically as live sperm
      concentration decreased. The SQI was most sensitive to live sperm concentrations
      from 11 to 232 x 10(6) sperm/mL. The SQI for semen diluted 10-fold was the best
      predictor of fertility when inseminating with a constant volume of 4-fold diluted
      semen (r = 0.71). When hens were inseminated with a constant 45 x 10(6)
      sperm/hen, the SQI for semen diluted 10- and 25-fold as well as to a constant
      concentration of 180 x 10(6) sperm/ mL was equally effective at predicting
      fertility (r = 0.59, 0.52, and 0.61, respectively). Apparently, the SQI is
      predictive of fertility when semen samples are diluted 10-fold prior to analysis
      regardless of insemination method used. Dilution beyond 10-fold appears to alter
      semen quality, rendering the SQI less accurate.

PMID- 14653481
TI  - What it's like to be a Red Sox fan.

PMID- 14653480
TI  - Effects of replacement finisher feed and length of feed withdrawal on broiler
      carcass yield and bacteria recovery.
AB  - A study was conducted to determine the effects of a replacement finisher feed
      (RF) on carcass yield and carcass bacteria recovery. RF is a commercial
      formulation of a D-glucose polymer (maltodextrin) with added salts and vitamins.
      Commercial male broilers (41 d of age) were given either RF or control-feed
      (traditional starter feed) for 8 h, followed by feed withdrawal for 0, 4, 8, or
      12 h before processing. During processing, whole carcass rinses (WCR) of pre
      eviscerated (feathers, feet, and heads removed) and eviscerated carcasses were
      analyzed for recovery of bacteria. Body weight at initiation of feed withdrawal
      (catch weight) or at slaughter (dock weight) did not differ significantly due to
      type of feed. Live shrink, as a percentage of live weight, increased
      significantly with time off feed. Birds fed RF exhibited significantly lower live
      shrink than the birds fed the control feed at 8 and 12 h after feed withdrawal.
      This difference between types of feed, RF or control, was approximately 0.1% per
      hour of feed withdrawal. Type of feed or length of feed withdrawal did not affect
      Campylobacter, coliform, or Escherichia coli counts recovered from WCR of pre
      eviscerated or eviscerated carcasses. These data demonstrate that feeding RF to
      broilers for 8 h before initiation of feed withdrawal may reduce live shrink
      without affecting carcass Campylobacter, coliforms, or E. coli recovered.

PMID- 14653482
TI  - Rehabilitation of the arthrofibrotic knee.
AB  - This paper describes the postoperative rehabilitation of the arthrofibrotic knee,
      with specific emphasis on modern rehabilitation techniques. The significance of
      prevention and early recognition is discussed. The importance of early motion and
      patellar mobility is emphasized and specific exercises to prevent and treat
      stiffness are described. Continuous passive motion, bracing, and exercise--on the
      stationary bicycle, on the treadmill, and in water--are adjuncts in the program.
      Strengthening is added when motion is re-established and there is no swelling or
      pain. Sport-specific activities are added if progress is satisfactory and motion
      is maintained. If pain, swelling, or stiffness develops, exercises should be
      discontinued. Modalities such as cryotherapy, ultrasound, electrical stimulation,
      rest, and manipulation can be used judiciously. Anti-inflammatory and analgesic
      medications should be used to prevent inflammation, to control pain, and to allow
      more aggressive rehabilitative exercises.

PMID- 14653483
TI  - Relationship of a low-lying muscle belly to tears of the peroneus brevis tendon.
AB  - A lack of information exists regarding predisposing factors to peroneus brevis
      tendon (PBT) tears. In 30 human cadaveric specimens, the location of the
      musculotendinous junction (MTJ) with respect to the fibula tip and peroneal
      tubercle was measured, as well as the tendon width. Degenerative longitudinal
      tears were found in 4 cases. The MTJ was significantly more distal and the tendon
      was thicker in torn versus untorn specimens (P < 0.05). The data suggest that
      longitudinal location of the peroneus brevis MTJ may have an influence on the
      development of degenerative tears. This feature might be an important clinical
      risk factor for the development of PBT tears and warrants further clinical
      investigation.

PMID- 14653484
TI  - Avulsion fractures of the medial and lateral malleoli of the ankle in cadavers:
      new radiographic projections for improved diagnosis.
AB  - The malleolar attachment sites of the tibionavicular (TN), tibiocalcaneal (TC),
      posterior tibiotalar (PTT), anterior talofibular (ATF), and calcaneofibular (CF)
      ligaments of 3 cadaveric ankles were dissected. Standard and new radiographic
      projections of the ankle were obtained with the foot in different positions and
      various degrees of beam angulation. Simulated avulsion injuries related to these
      ligaments were created, and the visibility of these structures was assessed.
      Avulsion injuries of the TN ligament were better assessed in the plantar-flexed
      radiographs with lateral beam angulation. Standard projections were found to
      adequately depict avulsion fractures related to the TC and CF ligaments.
      Radiographs in external ankle rotation were best for evaluating injuries of the
      PTT ligament. Avulsion injuries related to the ATF ligament were best visualized
      in the plantar-flexed views with medial beam angulation. Modified radiographic
      projections of the ankle improve visualization of ligamentous structures of the
      malleoli and avulsion injuries related to those.

PMID- 14653485
TI  - Nonunion of femoral neck fracture and trochanteric osteotomy after a pinned,
      slipped capital femoral epiphysis: a case report.
AB  - Femoral neck fracture as a complication of slipped capital femoral epiphysis
      (SCFE) is rare. Even rarer is a femoral neck nonunion as an additional
      complication. This is the first case reported in the literature of a failed
      valgus osteotomy for a femoral neck nonunion. A salvage operation involving a
      step-cut valgus/flexion/internal rotation osteotomy, open reduction and internal
      fixation, with a blade plate and cannulated screw, placement of an allograft
      femoral strut, and allograft bone grafting was successfully performed. Femoral
      neck fractures following SCFE fixation are more difficult to treat because of
      abnormal femoral neck configuration. Therefore a valgus, flexion, and internal
      rotation producing osteotomy may need to be initially performed to prevent a
      femoral neck nonunion.

PMID- 14653486
TI  - Torticollis in an infant caused by hereditary muscle aplasia.
AB  - Torticollis is a common condition presenting to the general or pediatric
      orthopedist. We describe the case of a child with severe torticollis caused by a
      hereditary unilateral absence of the sternocleidomastoid and trapezius muscles.
      Both his father and paternal grandfather had a forme fruste, with similar but
      milder findings. Electromyography and cross-sectional imaging were valuable in
      making the diagnosis. We believe this is the first reported case of hereditary
      unilateral muscle aplasia presenting as torticollis in an infant.

PMID- 14653487
TI  - Injury to the developing sternum in an adolescent football player: a case report
      and literature review.
AB  - When a blow to the sternum causes pain in a young athlete, the differential
      diagnosis can be complicated by persistence of an unfused growth center that does
      not normally fuse until age 18. We report a case of physeal injury in the sternum
      that was originally diagnosed as a stress fracture. The young football player in
      this case may have been predisposed to such an injury by abnormal synostosis of
      the sternomanubrial junction.

PMID- 14653488
TI  - Pyomyositis in a 69-year-old tennis player.
AB  - Pyomyositis is an acute bacterial infection of skeletal muscle usually caused by
      Staphylococcus aureus. Outside of tropical areas, pyomyositis is rare, especially
      in an otherwise healthy individual. We present a case of a 69-year-old tennis
      professional who developed pyomyositis of the piriformis muscle following a
      tennis tournament. We discuss the literature on pyomyositis and the need for high
      clinical suspicion in the diagnosis of this disorder, as well as the need for
      early aggressive antibiotic treatment.

PMID- 14653489
TI  - Treatment of supracondylar femur nonunions with open reduction and internal
      fixation.
AB  - We reviewed a consecutive series of 22 adults with 22 supracondylar femoral
      nonunions treated with open reduction and internal fixation (ORIF) to determine
      the results and complications associated with the procedure. Twenty-one of 22
      nonunions (95%) healed. Knee Society pain scores improved from 18 to 88 (P <
      0.001). Mean Knee Society functional scores improved from 4 to 55 (P < 0.001).
      Mean range of motion at follow-up was 1 degree to 96 degrees. ORIF and bone
      grafting of properly selected patients with nonunions of the distal femur
      resulted in high rate of union with few associated complications. All patients
      had improvement in pain scores and the great majority had improvements in
      functional scores.

PMID- 14653490
TI  - Freeing the arthroscope of particulate debris.
AB  - A simple technique is detailed for quickly clearing the tip of the arthroscope of
      particulate debris that may become lodged there while it is in place in the
      joint. Two or 3 taps with the back end of a Mayo scissors (or an instrument of
      equal weight) on the scope where it enters the joint should suffice. The taps
      must not be too firm, for fear of damaging the scope's fiberoptic cables.

PMID- 14653491
TI  - Humeral pseudocyst.

PMID- 14653492
TI  - Towards sustainable production of protein-rich foods: appraisal of eight crops
      for Western Europe. PART II: Analysis of the technological aspects of the
      production chain.
AB  - Increased production of plant protein is required to support the production of
      protein-rich foods which can replace meat in the human diet to reduce the strain
      that intensive animal husbandry poses on the environment. The suitability of
      lupin (Lupinus spp.), pea (Pisum sativum), quinoa (Chenopodium quinoa Willd.),
      triticale (x Triticosecale), lucerne (Medicago sativa), grasses (Lolium and
      Festuca spp.), rapeseed/canola (Brassica napus) and potato (Solanum tuberosum)
      for protein production in Western Europe was studied on the basis of a chain
      approach. The technological aspects, which are considered in this paper, are the
      processing methods, and the functional and nutritional properties of the derived
      protein products. The overall evaluation of the technological prospects of the
      eight crops as a protein source for Western Europe leads to the conclusion that
      this part of the production chain is not decisive for that choice. Pea and lupin
      have a slight advantage over the other crops, because their concentrates and
      isolates are already commercially available.

PMID- 14653493
TI  - New trends in food processing.
AB  - In this work some of the newest trends in food processing are reviewed. This
      revision intends to provide an updated overview (including works published until
      February 2001) on the newest food processes, including food manufacturing,
      preservation, and control. Modern processes for food and food ingredients
      manufacturing based on membrane technology, super-critical fluid technology, and
      some applications of biotechnology are presented, mainly applied to obtain
      functional foods, "all-natural" enriched foods, probiotics and prebiotics. Also
      included is a critical assessment concerning non-thermal preservation techniques
      used for food preservation, such as high hydrostatic pressure, pulsed electric
      fields, ultrasound, pulsed light, hurdle systems, etc. Finally, a group of new
      analytical techniques (i.e., molecular techniques such as Polymerase Chain
      Reaction (PCR), food image analysis, and biosensors) and their use for food and
      process control is reviewed.

PMID- 14653494
TI  - Effects of combined pressure and temperature on enzymes related to quality of
      fruits and vegetables: from kinetic information to process engineering aspects.
AB  - Throughout the last decade, high pressure technology has been shown to offer
      great potential to the food processing and preservation industry in delivering
      safe and high quality products. Implementation of this new technology will be
      largely facilitated when a scientific basis to assess quantitatively the impact
      of high pressure processes on food safety and quality becomes available. Besides,
      quantitative data on the effects of pressure and temperature on safety and
      quality aspects of foods are indispensable for design and evaluation of optimal
      high pressure processes, i.e., processes resulting in maximal quality retention
      within the constraints of the required reduction of microbial load and enzyme
      activity. Indeed it has to be stressed that new technologies should deliver,
      apart from the promised quality improvement, an equivalent or preferably enhanced
      level of safety. The present paper will give an overview from a quantitative
      point of view of the combined effects of pressure and temperature on enzymes
      related to quality of fruits and vegetables. Complete kinetic characterization of
      the inactivation of the individual enzymes will be discussed, as well as the use
      of integrated kinetic information in process engineering.

PMID- 14653495
TI  - SpikeNET: an event-driven simulation package for modelling large networks of
      spiking neurons.
AB  - Many biological neural network models face the problem of scalability because of
      the limited computational power of today's computers. Thus, it is difficult to
      assess the efficiency of these models to solve complex problems such as image
      processing. Here, we describe how this problem can be tackled using event-driven
      computation. Only the neurons that emit a discharge are processed and, as long as
      the average spike discharge rate is low, millions of neurons and billions of
      connections can be modelled. We describe the underlying computation and
      implementation of such a mechanism in SpikeNET, our neural network simulation
      package. The type of model one can build is not only biologically compliant, it
      is also computationally efficient as 400 000 synaptic weights can be propagated
      per second on a standard desktop computer. In addition, for large networks, we
      can set very small time steps (< 0.01 ms) without significantly increasing the
      computation time. As an example, this method is applied to solve complex
      cognitive tasks such as face recognition in natural images.

PMID- 14653496
TI  - Detecting dynamical changes within a simulated neural ensemble using a measure of
      representational quality.
AB  - Technological advances allowing simultaneous recording of neuronal ensembles have
      led to many developments in our understanding of how the brain performs neural
      computations. One key technique for extracting information from neural
      populations has been population reconstruction. While reconstruction is a
      powerful tool, it only provides a value and gives no indication of the quality of
      the representation itself. In this paper, we present a mathematically and
      statistically justified measure for assessing the quality of a representation in
      a neuronal ensemble. Using a simulated neural network, we show that this measure
      can distinguish between system states and identify moments of dynamical change
      within the system. While the examples used in this paper all derive from a
      standard network model, the measure itself is very general. It requires only a
      representational space, measured tuning curves, and neural ensembles.

PMID- 14653497
TI  - High-frequency, depressing inhibition facilitates synchronization in globally
      inhibitory networks.
AB  - Motivated by the study of sharp wave-associated ripples, high-frequency
      (approximately 200 Hz) extracellular field oscillations observed in the CA1
      region of the rat hippocampus during slow-wave sleep and periods of behavioural
      immobility, we consider a single inhibitory neuron synapsing onto a network of
      uncoupled, excitatory neurons. The inhibitory synapse is depressing and has a
      small synaptic delay. Each excitatory cell provides instantaneous, positive
      feedback to the inhibitory cell. We show that the interneuron can rapidly
      synchronize the action potentials of the pyramidal cells if the frequency of
      inhibitory input is increased in a ramp-like manner as occurs during the ripple.
      We show that the basin of attraction of the synchronous solution is larger when
      the inhibition frequency is gradually increased as opposed to remaining constant.

PMID- 14653498
TI  - Measuring linear and quadratic contributions to neuronal response.
AB  - We present a method to dissociate the sign-dependent (linear or odd-order)
      response from the sign-independent (quadratic or even-order) response of a neuron
      to sequences of random orthonormal stimulus elements. The method is based on a
      modification of the classical linear-nonlinear model of neural response. The
      analysis produces estimates of the stimulus features to which the neuron responds
      in a sign-dependent manner, the stimulus features to which the neuron responds in
      a sign-independent manner and the relative weight of the sign-independent
      response. We propose that this method could be used to characterize simple and
      complex cells in the primary visual cortex.

PMID- 14653499
TI  - Modulation of excitatory synaptic coupling facilitates synchronization and
      complex dynamics in a biophysical model of neuronal dynamics.
AB  - In this paper, complex dynamical synchronization in a non-linear model of a
      neural system is studied, and the computational significance of the behaviours is
      explored. The local neural dynamics is determined by voltage- and ligand-gated
      ion channels and feedback between densely interconnected excitatory and
      inhibitory neurons. A mesoscopic array of local networks is modelled by
      introducing coupling between the local networks via weak excitatory-to-excitatory
      connectivity. It is shown that with modulation of this long-range synaptic
      coupling, the system undergoes a transition from independent oscillations to
      stable chaotic synchronization. Between these states exists a 'weakly' stable
      state associated with complex, intermittent behaviour in the temporal domain and
      clusters of synchronous regions in the spatial domain. The paper concludes with a
      discussion of the putative relevance of such processes in the brain, including
      the role of neuromodulatory systems and the mechanisms underlying sensory
      perception, adaptation, computation and complexity.

PMID- 14653500
TI  - Input-output statistical independence in divisive normalization models of V1
      neurons.
AB  - Simoncelli and co-workers have proposed statistically-derived nonlinear divisive
      normalization models of the primary visual cortex (V1) that are consistent with
      the hypothesis that sensory systems are adapted to the signals to which they are
      exposed. In this paper, we present a more rigorous mathematical formulation and
      analysis of these statistically-derived models in terms of mutual information as
      a metric for statistical independence. We prove that the ad hoc choice of
      divisive normalization parameters proposed by Simoncelli and co-workers does not
      guarantee statistical independence between the output responses, but
      interestingly such choice does guarantee that each output response is
      statistically independent of almost all the linear inputs. This holds for the two
      different models of natural image statistics analysed theoretically, and is
      consistent with empirical results obtained on a set of natural images.

PMID- 14653501
TI  - Influence of membrane properties on spike synchronization in neurons: theory and
      experiments.
AB  - In the brain spike synchronization in neurons is involved in information transfer
      and certain forms of dysfunction. The theory of random point processes was used
      to relate the statistical properties of input point processes to synchronization
      between firing in neurons viewed as threshold devices. Derived analytical
      relations describe normalized synchronization in the case of shared input with
      balanced excitation and inhibition. For neuronal models with unbalanced shared
      input and spike generating Hodgkin-Huxley type conductances, the theory
      satisfactorily describes the temporal dependence of spike synchronization on the
      delay between spikes. Computer generated stochastic stimulus current was used to
      stimulate motoneurons in turtle spinal cord slices. Theory was able to
      approximate the temporal dependence of spike synchronization on the delay between
      spikes when the membrane time constant and the relative spike threshold measured
      were used in calculations. In agreement with the theoretical prediction,
      normalized spike synchrony was reduced when the threshold for spike generation
      was lowered by injection of steady depolarizing bias current. In spinal
      motoneurons the relative spike threshold can be lowered by a persistent inward
      current facilitated by activation of certain metabotropic transmitter receptors.
      After induction of this inward current spike synchronization was reduced several
      times. It is suggested that downregulation of the persistent inward current in
      motoneurons by disruption of brainstem modulatory systems, as in Parkinson
      disease, can facilitate tremor due to the increased synchrony between
      motoneurons.

PMID- 14653502
TI  - Quadratic forms in natural images.
AB  - Several studies have succeeded in correlating natural image statistics with
      receptive field properties of neurons in the primary visual cortex. If we
      determine the parameters of linear transformations that make their output values
      as independent as possible when input data are natural images, we obtain
      parameter values that correspond to simple cell characteristics. It was also
      proved that, by making output values as temporally coherent as possible, simple
      cell characteristics also emerge. However, complex cell properties have not been
      fully explained by previous studies of natural image statistics. In this study,
      we examine whether we could reproduce complex cell properties by determining the
      parameters of two-layer networks that make their outputs as independent and
      sparse as possible or as temporally coherent as possible. Input-output functions
      of two-layer networks correspond to quadratic forms and they form a class of
      functions that includes complex cell responses and many other functions.
      Therefore, we employed two-layer networks as a framework for discussing complex
      cell properties as in previous studies. By maximizing the independence and
      sparseness of output values of two-layer networks without considering the
      temporal structure of input images, squared responses of simple cells are
      obtained and complex cell properties are not reproduced. On the other hand, by
      maximizing the temporal coherence of output, we obtain complex cell properties
      among other kinds of input-output functions. In previous studies, the measure of
      temporal coherence was the squared difference between the responses to two
      consecutive input images. We obtain two-layer networks that minimize this measure
      and show that some of them exhibit properties of complex cells but not clearly.
      We propose the sparseness of difference between responses to two consecutive
      inputs as an alternative measure of temporal coherence. We formulate an algorithm
      to maximize the sparseness of difference and show that complex cell properties
      emerge more clearly.

PMID- 14653503
TI  - A working memory model based on fast Hebbian learning.
AB  - Recent models of the oculomotor delayed response task have been based on the
      assumption that working memory is stored as a persistent activity state (a 'bump'
      state). The delay activity is maintained by a finely tuned synaptic weight matrix
      producing a line attractor. Here we present an alternative hypothesis, that fast
      Hebbian synaptic plasticity is the mechanism underlying working memory. A
      computational model demonstrates a working memory function that is more resistant
      to distractors and network inhomogeneity compared to previous models, and that is
      also capable of storing multiple memories.

PMID- 14653504
TI  - The effects of spontaneous activity, background noise, and the stimulus ensemble
      on information transfer in neurons.
AB  - Information theory is playing an increasingly important role in the analysis of
      neural data as it can precisely quantify the reliability of stimulus-response
      functions. Estimating the mutual information between a neural spike train and a
      time varying stimulus is, however, not trivial in practice and requires
      assumptions about the specific computations being performed by the neuron under
      study. Consequently, estimates of the mutual information depend on these
      assumptions and their validity must be ascertained in the particular
      physiological context in which experiments are carried out. Here we compare
      results obtained using different information measures that make different
      assumptions about the neural code (i.e. the way information is being encoded and
      decoded) and the stimulus ensemble (i.e. the set of stimuli that the animal can
      encounter in nature). Our comparisons are carried out in the context of
      spontaneously active neurons. However, some of our results are also applicable to
      neurons that are not spontaneously active. We first show conditions under which a
      single stimulus provides a good sample of the entire stimulus ensemble.
      Furthermore, we use a recently introduced information measure that is based on
      the spontaneous activity of the neuron rather than on the stimulus ensemble. This
      measure is compared to the Shannon information and it is shown that the two
      differ only by a constant. This constant is shown to represent the information
      that the neuron's spontaneous activity transmits about the fact that no stimulus
      is present in the animal's environment. As a consequence, the mutual information
      measure based on spontaneous activity is easily applied to stimuli that mimic
      those seen in nature, as it does not require a priori knowledge of the stimulus
      ensemble. Finally, we consider the effect of noise in the animal's environment on
      information transmission about sensory stimuli. Our results show that, as
      expected, such 'background' noise will increase the trial-to-trial variability of
      the neural response to repeated presentations of a stimulus. However, the same
      background noise can also increase the variability of the spike train and hence
      can lead to increased information transfer in the presence of background noise.
      Our study emphasizes how different assumptions can lead to different predictions
      for the information transmission of a neuron. Assumptions about the computations
      being performed by the system under study as well as the stimulus ensemble and
      background noise should therefore be carefully considered when applying
      information theory.

PMID- 14653505
TI  - A study on the mineral depletion of the foods available to us as a nation over
      the period 1940 to 1991.
AB  - In 1927 a study at King's College, University of London, of the chemical
      composition of foods was initiated by Dr McCance to assist with diabetic dietary
      guidance. The study evolved and was then broadened to determine all the important
      organic and mineral constituents of foods, it was financed by the Medical
      Research Council and eventually published in 1940. Over the next 51 years
      subsequent editions reflected changing national dietary habits and food laws as
      well as advances in analytical procedures. The most recent (5th Edition)
      published in 1991 has comprehensively analysed 14 different categories of foods
      and beverages. In order to provide some insight into any variation in the quality
      of the foods available to us as a nation between 1940 and 1991 it was possible to
      compare and contrast the mineral content of 27 varieties of vegetable, 17
      varieties of fruit, 10 cuts of meat and some milk and cheese products. The
      results demonstrate that there has been a significant loss of minerals and trace
      elements in these foods over that period of time. It is suggested that the
      results of this study cannot be taken in isolation from recent dietary,
      environmental and disease trends. These trends are briefly mentioned and
      suggestions are made as to how the deterioration in the micronutrient quality of
      our food intake may be arrested and reversed.

PMID- 14653506
TI  - Recommendations of the First Conference on Obesity and Physical Activity in the
      Arab countries. Held in Bahrain, 24-26 September, 2002.

PMID- 14653507
TI  - A review of some statistics on breastfeeding in Saudi Arabia.
AB  - Breastfeeding is the ideal and most natural way of nurturing infants. The
      importance of breastfeeding has been proved unequivocally, and UNICEF and WHO
      have issued guidelines to ensure breastfeeding. Saudi Arabia is a country where
      the legislation is derived from the Quran and Hadiths. The Holy Quran says that
      the mothers shall give suck to their offspring for two complete years.... The
      majority of mothers start breastfeeding their infants but soon introduce bottles.
      The single most common reason cited for the early introduction of bottle feeding
      is that the breast milk is insufficient. Because of this tendency, many mothers
      practice mixed feeding. The duration of breastfeeding varies but in general it is
      done beyond six months, and various factors affect the duration. Researchers have
      recently started using the WHO recommended key breastfeeding indicators. In a
      study these key indicators were found to be very low. The authors feel that there
      is a need to revise the media campaign for promoting breastfeeding utilizing the
      instructions and guidance from the Holy Quran and Hadiths.

PMID- 14653509
TI  - Assessment of knowledge and practice of nutritional and life style risk factors
      associated with cancer among hospital workers at two university teaching
      hospitals in Osun State, Nigeria.
AB  - The objectives of this study were to assess both the predisposing and
      precipitating risk factors in the aetiology of any form of cancer among hospital
      workers at two teaching Hospitals in Osun State, Nigeria. Pre-tested and modified
      questionnaires were administered to 250 respondents. One hundred and seventy
      questionnaires were duly filled and completed. Less than 9% of the respondents
      consumed fruits and vegetables on a daily basis; while the highest percentage
      (65%) regularly consumed butter/margarine, followed with consumption of red meat.
      Twenty nine percent (29%) from both locations were classified as overweight and
      obese. Half did physical exercise twice a week. Of the 168 respondents. 34
      (20.2%) did meet the criteria for completely emptying their bowels within a
      specified time of three minutes. It is concluded that whilst predisposing risk
      factors do not pose a threat to the onset of any form of cancer among
      respondents, precipitating factors are real major factors that need to be
      addressed through information, education and communication (I.E.C). Such an
      I.E.C. should be geared towards promotion of healthy eating and life style
      strategies. Alter all, 'the first step in cancer prevention is knowing the risk
      profile'.

PMID- 14653508
TI  - Effect of fungi fermentation on organoleptic properties, energy content and in
      vitro multienzyme digestibility of cassava products (flour & gari).
AB  - The present study sought to investigate the effect of fungi fermentation on the
      energy content, sensory quality and the digestibility (in vitro) of cassava
      products (flour and gari). The fungi fermented cassava products (gari and flour)
      were produced, by fermenting cassava mash with pure strains of some common
      saprophytes, namely, Aspergillus flavus, Aspergillus niger, Rhizopus oryzae and
      Saccharomyces spp (Baker's yeast and palm wine yeast) for 72 hrs before
      processing into cassava flour and gari, the forms in which cassava is popularly
      consumed in Nigeria. Parameters determined include energy (Bomb calorimetry),
      digestibility (in vitro) and sensory quality by trained taste panel. The results
      of the study indicated that fungi fermentation of the cassava mash significantly
      (P < 0.05) increased the acceptability of the colour, texture, aroma and taste of
      the "gari", with that of Rhizopus oryzae fermentation having the highest general
      acceptability. Furthermore, the results also indicated that fungi fermentation of
      cassava mash significantly increased (P < 0.05) the in vitro multienzyme protein
      digestibility of the cassava products. In view of this, fungi fermentation could
      be used to improve the sensory quality and protein digestibility of cassava
      products without any significant (P > 0.05) effect on the energy-giving role of
      cassava products.

PMID- 14653510
TI  - Development, acceptability and nutrient composition of traditional supplementary
      foods consumed by lactating women in India.
AB  - Some recipes consumed during lactation were, for the first time, standardized,
      and analysed for nutritional composition and organoleptic evaluation. Results
      revealed that protein, fibre and ash contents were maximum in Ajwain (omum
      seeds). The total Ca, Fe, Zn, Cu and P was also highest in Ajwain followed by
      Gond Panjiri, Kangni and Halwa. The available minerals were also higher in Ajwain
      as compared to other foods. The in vitro protein and starch digestibility was in
      the range of 55.97 to 75.30 and 43.56 to 47.57 per cent, respectively, in
      different traditional supplementary foods. Organoleptically, all the foods
      prepared were found to be acceptable in terms of colour, flavour, taste, texture
      and appearance.

PMID- 14653511
TI  - Evolutionary nutrition: dietary quality and generational health.

PMID- 14653512
TI  - Combination antifungal therapy against Candida species: the new frontier--are we
      there yet?
AB  - In the past decade, we have seen a significant increase in the incidence of
      invasive fungal infections. In addition, opportunistic fungal infections
      resistant to antifungal agents have become increasingly common and their
      frequency will more than likely continue to increase. The antifungal
      armamentarium for the treatment of serious fungal infections remains limited. A
      possible approach to overcoming antifungal drug resistance and high mortality
      rates seen in severe fungal infections is to combine two or three classes of
      antifungals, especially if the drugs have different mechanisms of action. The
      unique properties of newer antifungals now provide us with the opportunity to
      investigate antifungal combinations that may become the standard of care for
      serious fungal infections. Combinations of new agents along with more traditional
      antifungals have now been shown to possess some synergistic or at least additive
      activity against Candida in clinical trials. On the other hand, caution is still
      needed since other antifungal combinations have demonstrated antagonistic
      activity in vitro. Well-controlled clinical trials are needed to define the most
      efficacious antifungal regimen. Furthermore, these trials should also evaluate
      the side effect potential of combination regimens and the pharmacoeconomic impact
      these regimens may have. Thus, while much optimism exists for combination
      therapy, there is much yet to be done.

PMID- 14653513
TI  - Rapid identification of fungi by sequencing the ITS1 and ITS2 regions using an
      automated capillary electrophoresis system.
AB  - We developed a standardized DNA sequence-based approach for the accurate and
      timely identification of medically important fungi by sequencing polymerase chain
      reaction (PCR) products with a rapid automated capillary electrophoresis system.
      A simple DNA extraction method and PCR amplification using universal fungal
      primers was used to amplify ribosomal DNA from a range of clinical isolates and
      reference strains. The entire internal transcribed spacer (ITS) 1-5.8S-ITS2
      ribosomal DNA region was sequenced using automated dye termination sequencing for
      89 clinical isolates. These had previously been identified by traditional methods
      and included 12 ascomycetous yeast species, three basidiomycetous yeast species,
      eight dermatophyte species and two thermally dimorphic fungi, Scedosporium
      prolificans and S. apiospermum. Furthermore, 21 reference strains representing 19
      different Candida species, Geotrichum candidum and Malassezia furfur were also
      sequenced as part of this study and were used either as standards for sequence
      based comparisons, or as assay controls. Sequence-based identification was
      compared to traditional identification in a blinded manner. Of the clinical
      isolates tested, 88/89 had DNA sequences that were highly homologous to those of
      reference strains accessioned in GenBank, and 87/89 gave a sequence-based
      identification result that correlated with the traditional identification. In
      contrast to relatively slow conventional methods of identification, a sequence
      based identification from a pure culture can be obtained within 24 h of a DNA
      extraction carried out after a minimal period of culture growth. We conclude that
      this approach is rapid, and may be a more accurate cost-effective alternative
      than most phenotypic methods for identification of many medically important fungi
      frequently encountered in a routine diagnostic microbiology laboratory.

PMID- 14653514
TI  - Genetic characterization of environmental isolates of the Cryptococcus neoformans
      species complex from Brazil.
AB  - The genetic affiliation of a large number of isolates of the Cryptococcus
      neoformans species complex from environmental sources in Brazil has been
      investigated using amplified fragment length polymorphism (AFLP). The strains of
      C. neoformans isolated from a single tree, as well as from neighbouring trees,
      showed high similarity values (> 95%) of their AFLP patterns, thus suggesting
      considerable genetic homogeneity. The majority of isolates of C. neoformans
      belonged to AFLP genotype 1, and had serotype A and mating type alpha (= C.
      neoformans var. grubii). Three isolates belonged to AFLP genotype 2, with
      serotype D and mating type alpha (= C. neoformans var. neoformans). One isolate,
      obtained from a building in Rio de Janeiro inhabited by pigeons, belonged to the
      AD hybrid AFLP genotype 3. All isolates from trees of C. neoformans var. gattii
      (= C. gattii) belonged to AFLP genotype 6, and their banding patterns showed
      relatively low genetic homogeneity with a similarity value of about 76%. Isolates
      of this genotype occupy an environmental niche in the Americas, and they may
      cause disease in non-AIDS and AIDS patients as well.

PMID- 14653515
TI  - Production of pro-inflammatory cytokines during the early stages of experimental
      Paracoccidioides brasiliensis infection.
AB  - Pro-inflammatory cytokines play an important role in both recruitment and
      activation of leukocytes migrating into tissues in response to invading
      pathogens. In this study the production of pro-inflammatory cytokines, determined
      by ELISA assays, and the recruitment of leukocytes into the lungs of BALB/c mice
      infected with Paracoccidioides brasiliensis conidia were evaluated during the
      early stages of infection. The results showed that infected mice had a
      significant increase in leukocytes in the lung during the first 4 days with a
      peak at day 2 post-challenge; infiltrates were composed mainly of
      polymorphonuclear neutrophils (PMN). Pro-inflammatory cytokines such as tumour
      necrosis factor alpha (TNF-alpha), interleukin (IL) 6, IL-1beta and macrophage
      inflammatory protein (MIP) 2 were produced at elevated levels during the first 4
      days post-challenge, but only in pulmonary samples and not in sera. Additionally,
      during the early stages of infection, overall weight loss was recorded in
      infected mice. These results suggest that pro-inflammatory cytokines could be
      responsible for the recruitment of leukocytes into the lung during the early
      stages of P. brasiliensis infection. In addition, both pro-inflammatory cytokine
      production and leukocyte recruitment may participate in the control of infection
      by influencing the organization of the immune response in the host exposed to P.
      brasiliensis conidia.

PMID- 14653517
TI  - Clinical aspects of Candida species carriage in saliva of xerotomic subjects.
AB  - In order to investigate the clinical factors that might influence the diversity
      and the degree of Candida species carriage in saliva, we conducted a cross
      sectional study with 133 patients with complaints of xerostomia. Anamnesis, oral
      examination and collection of chewing-stimulated whole saliva were performed. The
      samples of saliva were kept refrigerated until they were plated onto CHROMagar
      Candida; cfu were counted and Candida species were identified by standard
      methods. There was a high prevalence of mixed Candida colonization. No
      relationship was found between total Candida cfu counts and variables like
      gender, age, place of origin, underlying diseases, exposure to medications
      (except antibiotics), daily habits and salivary flow rates. Oral candidiasis,
      antibiotic exposure and dental prosthesis wearing were associated with relatively
      high Candida counts in saliva. Low salivary flow rates predisposed to intense
      colonization by C. albicans and C. parapsilosis.

PMID- 14653518
TI  - Antifungal activity of fluconazole in combination with lovastatin and their
      effects on gene expression in the ergosterol and prenylation pathways in Candida
      albicans.
AB  - The sterol pathway in Candida albicans is the target for several classes of
      antifungal drugs. Intermediates in the sterol pathway are involved in ergosterol
      synthesis, prenylation and dolichol synthesis. This study examines gene
      expression of the sterol pathway in response to lovastatin, an inhibitor of HMG
      CoA reductase (Hmg1p), and fluconazole, an inhibitor of 14 alpha-lanosterol
      demethylase (Erg11p). Minimum inhibitory concentration (MIC) studies indicated
      that lovastatin acts synergistically with fluconazole in vitro. Semi-quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) results indicated that
      genes in the early part of the sterol pathway, such as HMG1 and ERG20, did not
      alter expression in the presence of both lovastatin and fluconazole, whereas
      genes in the later part of the sterol pathway, such as ERG9 and ERG11, had
      increased expression in response to these drugs in mid-logarithmic growth. Genes
      involved in prenylation, such as RAM1 and RAM2, also respond to these drugs in
      mid-logarithmic growth, although another prenylation gene, CDC43, was not
      affected. After 24 h of growth, the relative expression of ERG20, ERG9, and ERG11
      remained unchanged or increased in the presence of both drugs, while all other
      genes decreased in expression under all drug treatments.

PMID- 14653516
TI  - Multiple experimental designs to evaluate the role of T-cell-mediated immunity
      against experimental vaginal Candida albicans infection.
AB  - Studies to date suggest a limited protective role for Candida-specific Th1-type
      cell-mediated immunity (CMI) against Candida albicans vaginitis, despite
      protection against other mucosal Candida infections. Recent evidence suggests
      this may be due to immunoregulatory mechanisms that inhibit a more profound CMI
      response against C. albicans vaginal infections. The present study was designed
      to conduct an evaluation of the protective role of CMI against experimental C.
      albicans vaginitis using multiple approaches, including the use of T-cell
      immunodeficient (SCID, Nude) and knockout (CD4) mice and several immunization
      designs in immunocompetent mice. Results showed, with few exceptions, that most T
      cell-immunodeficient or knockout mice had a vaginal fungal burden similar to that
      of wild-type strains throughout the observation period. In addition, no
      correlation was observed between vaginal T-helper and proinflammatory cytokines
      and fungal burden, suggesting a generalized state of immunoregulation. Evaluation
      of the effects of various immunization designs that included different Candida
      antigens, routes of delivery and strains of mice yielded no protection against
      vaginal candidiasis. These studies provide further evidence of a lack of a
      protective role of T cells against C. albicans vaginitis, and continue to support
      the concept of immunoregulation against vaginal CMI responses.

PMID- 14653519
TI  - Immunity and hypersensitivity to gp43 antigen in susceptible and resistant mice
      infected with Paracoccidioides brasiliensis.
AB  - Pathogenic mechanisms underlying paracoccidioidomycosis are still poorly
      understood. A well-established murine model of resistance (mouse lineage A/Sn)
      and susceptibility (lineage B10.A) to P. brasiliensis pulmonary infection was
      here employed to compare immune response to gp43, the major antigenic component
      of the fungus. Mice were infected and their cellular and humoral immunity to gp43
      were investigated for up to 16 weeks. In both mouse strains, challenge with gp43
      indistinguishably evoked a typical immediate-hypersensitivity response, followed
      by a 24-h late-phase reaction consistent with the same type of immunological
      activation. IL-4 was detected in cultures of gp43-stimulated lymph node cells
      only in susceptible animals 2 weeks post-infection, while IL-5 was found
      throughout the study in both mouse strains. IL-10 appeared in the supernatants of
      stimulated cells from resistant and susceptible animals in increasing amounts as
      infection advanced. Conversely, interferon (IFN)-gamma was produced under gp43
      stimulation only by cells from A/Sn animals. The humoral response was
      characterized by low levels of anti-gp43. Titration of IgG isotypes, however,
      revealed a predominance of IgG1. IgG2a levels were highest in resistant animals,
      whereas IgG2b levels were highest in susceptible mice. In conclusion, immunity
      induced by gp43 exhibits common features in A/Sn and B10.A phenotypes, such as
      immediate hypersensitivity, late phase reaction and high levels of IL-10, but
      some differences between the strains are also seen.

PMID- 14653520
TI  - Phaeohyphomycosis caused by Exophiala spinifera in India.
AB  - The second case of phaeohyphomycosis due to Exophiala spinifera in India has been
      diagnosed 46 years after the initial case. The present case involved a 12-year
      old female patient with no known immunocompromising conditions. She presented
      with multiple verrucous, well-defined plaques encompassing phaeohyphomycotic
      lesions of varying sizes on her face, chest, arms and thighs. Lymph node
      involvement in dissemination was confirmed by demonstrating pigmented fungal
      elements in histopathology of the left axillary node. The infection responded
      positively to prolonged administration of itraconazole. The original case
      involved a young boy and was similarly disseminated but was more severe, with
      bone involvement, and had a fatal outcome. It is likely that other such cases
      have occurred in the intervening time but have not been reported.

PMID- 14653521
TI  - A case of sporotrichosis treated with itraconazole.
AB  - Lymphocutaneous sporotrichosis is caused by Sporothrix schenckii, a dimorphic
      fungus commonly existing on decaying plants and in the soil. The fungus has a
      worldwide distribution but is more prevalent in temperate and tropical climates.
      Infection may result from traumatic inoculation of contaminated material such as
      soil, hay, moss, plant debris, splinters, thorns and barbs. Inoculation is also
      possible through some animal scratches and bites. We describe a typical case of
      lymphocutaneous sporotrichosis, which was confirmed by clinical, histological and
      microbiological features. The patient was successfully treated with 400 mg daily
      systemic itraconazole for 4 months.

PMID- 14653522
TI  - First Italian report of onychomycosis caused by Onychocola canadensis.
AB  - Onychocola canadensis is a non-dermatophytic mould that has been associated with
      onychomycosis particularly in temperate climates. Until now, O. canadensis has
      been isolated from patients in Canada (14 cases), New Zealand (three), France
      (nine), UK (four) and Spain (two). We describe the first Italian case of
      onychomycosis caused by this fungus.

PMID- 14653523
TI  - Cavernicolous habitats harbouring Cryptococcus neoformans: results of a
      speleological survey in Apulia, Italy, 1999-2000.
AB  - Twenty-five caves of speleological and palaeontological interest were
      investigated for the presence of Cryptococcus spp. within the Apulia region of
      Italy. Five hundred and forty-five specimens of soil, mud, animal faeces, water
      and decayed animal and plant remains were examined. Faecal specimens from bats,
      pigeons and foxes in three caves yielded Cryptococcus neoformans var. neoformans
      and C. laurentii, C. neoformans var. neoformans and C. albidus were isolated from
      two soil specimens. Only three caves were positive for the presence of C.
      neoformans, but the survey documents the finding of a possible natural reservoir
      in Apulia. It is the first record of occurrence of this yeast in association with
      cavernicolous habitats, and indicates the potential role of caves in exposing
      speleologists to life-threatening fungal infections.

PMID- 14653524
TI  - Critical care research.

PMID- 14653525
TI  - An audit of post-operative nausea and vomiting, following cardiac surgery: scope
      of the problem.
AB  - Post-operative nausea and vomiting is a major problem for patients following
      cardiac surgery. The literature in this area identifies that there are a number
      of individual patient and post-operative factors which increase the risk of post
      operative nausea and vomiting, including female gender, non-smoker, age, use of
      opioids, pain and anxiety. An audit involving 200 patients, who had undergone
      cardiac surgery was implemented to assess/evaluate the incidence of nausea and
      vomiting for this patient group. Data collected included information relating to
      nausea and vomiting, pain, consumption of morphine and other individual patient
      variables. The results suggest that nausea and vomiting, is experienced by a
      large number of patients after cardiac surgery (67%), with the majority suffering
      on the first day after surgery. The duration of nausea and vomiting for most is
      short, but for a significant number (7%) it can last up to one-quarter of their
      initial post-operative course. The paper discusses key implications for practice
      arising from this project.

PMID- 14653526
TI  - Neonatal end-of-life care in Sweden.
AB  - A survey was carried out of Swedish neonatal end-of-life regarding practice
      before birth, at birth, during dying and after death using a descriptive
      questionnaire with close-ended questions and individual comments. The practice in
      32 of 38 neonatal units, as described by the head nurse or the registered nurses,
      was largely similar. Respectful treatment of both the neonate and the parents
      during neonatal end-of-life care was indicated. Differences were found in pre
      natal care concerning the information about the risks of pre-term birth, the
      opportunity for parents to view a pre-term neonate and meet its family, as well
      as a social worker. Practice directly after birth was also different. A little
      less than half of the units answered that they gave a description of the
      seriously ill neonate to the parents before the first visit to the ward. Practice
      during dying indicated that only a few units permitted the neonate to die at
      home.

PMID- 14653527
TI  - Designing a grounded theory study: some practicalities.
AB  - Grounded theory is an interpretative research methodology frequently used by
      social science researchers seeking to discover the underlying social processes
      shaping interaction. The methodology is useful to create knowledge about the
      behavioural patterns of a group. The aim of this paper was to discuss some
      practical issues that the prospective grounded theory researcher planning a small
      scale project may consider. Discussion focuses on the basic premises, choosing a
      version of grounded theory, the research problem, the purpose of study, the
      research question and the place of the literature in a study. The specific skills
      required of the grounded theory researcher are considered and some cautions are
      exercised. The paper may assist student researchers in a critical care setting
      and may be of interest to their supervisors and experienced. grounded theory
      researchers.

PMID- 14653528
TI  - Monitoring the dying patient in ITU: a personalized discussion.

PMID- 14653529
TI  - Removing chest drains--a critical reflection of a complex clinical decision.
AB  - Decision-making is a fundamental element of nursing work (Boblin-Cummings et al,
      1999; Berggren and Severinsson, 2000; Bucknall, 2000) which fluctuates according
      to experience, location and personal boundaries. Nursing judgements are said to
      portray the nature of nursing knowledge and practice (Thompson, 1999; Buckingham
      and Adams, 2000a) and can affect others either favourably or adversely (Gordon et
      al., 1994), with Buckingham and Adams (2000a) emphasizing the benefits to be
      gained from understanding the process, including improved clinical effectiveness
      and self-knowledge. It is said that all decisions are made in one of two ways-
      hypothetico-deductively or intuitively (Dowie and Elstein, 1988; Thompson, 1999;
      Buckingham and Adams, 2000a)--although different titles are used interchangeably
      for the same modes. Both of these modalities are examined. Hypothetico-deductive
      reasoning entails exposure to information before and during the patient
      encounter. These data are grouped and used to generate a hypothesis or possible
      diagnosis. The second stance in decision-making is founded upon intuition and
      closely associated with expertise. The presence of chest drains after
      cardiothoracic surgery is known to cause severe pain, thereby interfering with
      respiratory mechanics and the ability to take part in physiotherapy exercises
      (Owen and Gould, 1997; Fox et al., 1999; Charnock and Evans, 2001; Lazzara,
      2002). This work therefore aims to examine the decision-making processes in
      relation to the prompt removal of chest drains by analysing the options available
      and the skills required to utilize them effectively.

PMID- 14653530
TI  - Rodent malaria parasites suffer from the presence of conspecific clones in three
      clone Plasmodium chabaudi infections.
AB  - We studied infection dynamics of Plasmodium chabaudi in mice infected with 3
      genetically distinct clones--1 less virulent than the other 2--either on their
      own or in mixtures. During the acute phase of infection, total numbers of asexual
      parasites in mixed-clone infections were equal to those produced by the 3 clones
      alone, suggesting strong in-host competition among clones. During the chronic
      phase of the infection, mixed-clone infections produced more asexual parasites
      than single-clone infections, suggesting lower levels of competition than during
      the acute phase, and indicating that a genetically diverse infection is harder to
      control by the host immune system. Transmission potential over the whole course
      of infection was lower from mixed-clone infections than from the average of the 3
      single-clone infections. These results suggest that in-host competition reduces
      both growth rate and probability of transmission for individual parasite clones.

PMID- 14653531
TI  - Sex ratios in the rodent malaria parasite, Plasmodium chabaudi.
AB  - The sex ratios of malaria and related Apicomplexan parasites play a major role in
      transmission success. Here, we address 2 fundamental issues in the sex ratios of
      the rodent malaria parasite, Plasmodium chabaudi. First we test the accuracy of
      empirical methods for estimating sex ratios in malaria parasites, and show that
      sex ratios made with standard thin smears may overestimate the proportion of
      female gametocytes. Secondly, we test whether the mortality rate differs between
      male and female gametocytes, as assumed by sex ratio theory. Conventional
      application of sex ratio theory to malaria parasites assumes that the primary sex
      ratio can be accurately determined from mature gametocytes circulating in the
      peripheral circulation. We stopped gametocyte production with chloroquine in
      order to study a cohort of gametocytes in vitro. The mortality rate was
      significantly higher for female gametocytes, with an average half-life of 8 h for
      female gametocytes and 16 h for male gametocytes.

PMID- 14653532
TI  - Togetherness among Plasmodium falciparum gametocytes: interpretation through
      simulation and consequences for malaria transmission.
AB  - Previous experimental gametocyte infections of Anopheles arabiensis on 3
      volunteers naturally infected with Plasmodium falciparum were conducted in
      Senegal. They showed that gametocyte counts in the mosquitoes are, like
      macroparasite intakes, heterogeneous (overdispersed). They followed a negative
      binomial distribution, the overdispersion coefficient seeming constant (k = 3.1).
      To try to explain this heterogeneity, we used an individual-based model (IBM),
      simulating the behaviour of gametocytes in the human blood circulation and their
      ingestion by mosquitoes. The hypothesis was that there exists a clustering of the
      gametocytes in the capillaries. From a series of simulations, in the case of
      clustering the following results were obtained: (i) the distribution of the
      gametocytes ingested by the mosquitoes followed a negative binomial, (ii) the k
      coefficient significantly increased with the density of circulating gametocytes.
      To validate this model result, 2 more experiments were conducted in Cameroon.
      Pooled experiments showed a distinct density dependency of the k-values. The
      simulation results and the experimental results were thus in agreement and
      suggested that an aggregation process at the microscopic level might produce the
      density-dependent overdispersion at the macroscopic level. Simulations also
      suggested that the clustering of gametocytes might facilitate fertilization of
      gametes.

PMID- 14653533
TI  - Leishmania (Viannia) braziliensis-induced chronic granulomatous cutaneous lesions
      affecting the nasal mucosa in the rhesus monkey (Macaca mulatta) model.
AB  - The present studies on infections with Leishmania (Viannia) braziliensis in
      rhesus macaques were made to characterize the evolution of different parasite
      strains and the immune responses they elicited in this experimental host. A
      standardized inoculum of promastigotes was injected intradermally either above
      the eyelid or on the forearm of each monkey. Sixteen infected monkeys developed
      longstanding infections which lasted until the end of the observation period (33
      months). The time required for lesion development was very variable, not only for
      the isolates showing molecular differences but also for individual animals in
      groups infected with the same parasite strain. The inocula produced lesions of
      variable severity, ranging from localized cutaneous leishmaniasis (CL) with a
      tendency to spontaneous healing to non-healing disease. One infected animal
      developed persistent metastatic skin and mucosal lesions. Anti-Leishmania
      antibodies and parasite-specific T-cell responses were induced by the
      experimental infections. As the granulomatous inflammatory response found at the
      lesions in L. (V.) braziliensis-infected M. mulatta was similar to that in
      patients with CL, this primate model could be useful for studying the
      pathophysiology and immunoregulatory events associated with disease evolution, as
      well as for the evaluation of new drugs or candidate vaccines.

PMID- 14653534
TI  - Immunolocalization of Leishmania (Viannia) braziliensis membrane antigens
      recognized by mAbs SST-2, SST-3, and SST-4.
AB  - The immunolocalization of Leishmania (Viannia) braziliensis stage-specific
      antigens recognized by mAbs was analysed by transmission electron microscopy. The
      antigen recognized by mAb SST-2 was present at the surface of promastigotes,
      including the flagellum and flagellar pocket. The reactivity of SST-2 with
      isolates of different serodemes showed a pronounced microheterogeneity in terms
      of the number of reactive bands within the low molecular weight range from 24 to
      33 kDa. The 180 kDa glycoprotein recognized by mAb SST-3 was present only in the
      flagellar membrane. SST-3 also recognized multiple discrete bands from 160 to 200
      kDa, as observed in several serodemes. In contrast, mAb SST-4, which recognizes a
      98 kDa antigen, showed weak labelling on the promastigote surface by transmission
      electron microscopy and indirect immunofluorescence. Based on Western blotting,
      indirect immunofluorescence, and solid-phase radioimmunoassay, the antigens
      recognized by mAbs SST-2, SST-3 and SST-4 were present in all L. (V.)
      braziliensis analysed, from 7 different serodemes.

PMID- 14653535
TI  - Observations on the musculature and isolated muscle fibres of the liver fluke,
      Fasciola hepatica.
AB  - The liver fluke, Fasciola hepatica relies on a well-developed muscular system,
      not only for attachment, but for many aspects of its biology. Despite this,
      little is known about the system beyond the gross organization of the main
      somatic muscle layers. In the present study, a range of techniques have been
      applied to F. hepatica in order to understand more about various aspects of
      muscle organization, biochemistry (in terms of muscle proteins) and identity of
      isolated muscle fibres. Scanning electron microscopy has provided a direct
      visualization in situ of the somatic muscle layers and the organization of the
      muscle fibres within the ventral sucker. The muscle bundles contributing to the
      main somatic muscle layers are made up of up to 10 individual muscle fibres.
      Phalloidin staining for actin, in conjunction with confocal microscopy, confirmed
      the presence of 2 main somatic muscle layers (outer circular, inner
      longitudinal), beneath which lies a third layer of oblique muscle fibres. The use
      of propidium iodide in combination with phalloidin staining for actin
      demonstrated that the cell bodies associated with the 2 main somatic muscle
      layers are situated beneath the longitudinal muscle layer and are connected to
      their respective muscle fibres by short cytoplasmic processes. Myosin
      immunoreactivity was demonstrated in the somatic muscle layers and in the muscle
      layers surrounding various organ systems within the fluke. Double labelling for
      actin and myosin confirmed the co-localization of the 2 muscle proteins in the
      muscle fibres of the ventral sucker. Muscle fibres from the somatic muscle layers
      and the ventral sucker have been isolated and images obtained with phase-contrast
      microscopy and scanning electron microscopy. The muscle fibres contain actin and
      myosin, but lack a nucleus, the connection with the cell body having been broken
      during the isolation procedure.

PMID- 14653536
TI  - Parasite infracommunity diversity in eels: a reflection of local component
      community diversity.
AB  - The intestinal macroparasite communities of freshwater eels (Anguilla anguilla)
      captured in the south of England from Windsor (River Thames) during August 2001,
      and Leckford (River Test) during late June/July 2000, are reported for the first
      time. Parasite component communities were among the most species rich and diverse
      recorded from European eels. A total of 13 intestinal macroparasite species were
      encountered during the study, 8 from each eel host population with 3 being common
      to both. Acanthocephalans, nematodes and cestodes were recovered from each host
      population. Eels from Windsor additionally harboured Nicolla gallica (Digenea),
      which was also the most prevalent and abundant macroparasite species in these
      hosts. Each component community followed a log normal rank abundance distribution
      and demonstrated reduced species dominance and increased species equitability
      compared with previous studies. As such, the study component communities were
      suitable for testing the hypothesis of low infracommunity diversity in European
      eel hosts. Specifically, this hypothesis predicts that the intestinal
      macroparasite infracommunities of European eels are species-poor, displaying low
      density and diversity with high dominance, irrespective of component community
      diversity, and that this may be more pronounced in UK host populations. This
      hypothesis was not upheld; study findings demonstrate that higher infracommunity
      diversity in eel hosts is possible, and suggest that infracommunity diversity in
      individual eel hosts may be a simple, stochastic reflection of component
      community diversity.

PMID- 14653537
TI  - Lead concentrations in Hymenolepis diminuta adults and Taenia taeniaeformis
      larvae compared to their rat hosts (Rattus norvegicus) sampled from the city of
      Cairo, Egypt.
AB  - Concentrations of lead, determined by electrothermal atomic absorption
      spectrometry, were compared between the cestodes Hymenolepis diminuta and Taenia
      taeniaeformis and its host rat (Rattus norvegicus). Rats were sampled at 2 sites,
      which differed in respect to lead pollution as quantified from road dust,
      adjacent to the city of Cairo, Egypt. Comparing lead levels among host tissues
      and the parasites the significantly highest accumulation was found in H.
      diminuta, followed by rat kidney and larvae of T. taeniaeformis. Calculation of
      bioconcentration factors showed that H. diminuta contained 36-, 29-, 6- and 6
      fold higher lead levels than intestinal wall, liver, kidney and larvae of T.
      taeniaeformis, at the more polluted site. At the less contaminated site lead
      bioconcentration factors for H. diminuta were found to be 87, 87 and 11 referred
      to intestine, liver and kidney of the host. Due to a high variability of the lead
      concentrations in H. diminuta it was not possible to indicate differences in
      metal pollution between both sampling sites. This variability may be influenced
      by different age structures of cestode infrapopulations. It is likely that
      younger worms contain lower metal levels than older worms due to a shorter
      exposure period. Thus, it is necessary to standardize the sampling of worms which
      should be used for indication purposes. Due to a lack of adequate sentinel
      species in terrestrial habitats more studies are required to validate and
      standardize the use of helminths as accumulation bioindicators in order to obtain
      mean values with low standard deviations. The host-parasite system rat-H.
      diminuta appears to be a useful and promising bioindication system at least for
      lead in urban ecosystems as rats as well as the tapeworm are globally distributed
      and easily accessible.

PMID- 14653538
TI  - TaqMan minor groove binder real-time PCR analysis of beta-tubulin codon 200
      polymorphism in small strongyles (Cyathostomin) indicates that the TAC allele is
      only moderately selected in benzimidazole-resistant populations.
AB  - TaqMan minor groove binder probes were evaluated as to their suitability for the
      real-time allelic discrimination of the beta-tubulin codon 200 TTC/TAC single
      nucleotide polymorphism in cyathostomin species. Amplification of titrated cloned
      full-length beta-tubulin cDNA revealed that the TaqMan minor groove binder PCR is
      capable of specifically detecting as few as 10 copies. Testing of DNA from single
      adult and larval stages of several different species of cyathostomin allowed
      reproducible genotyping of individual worms. Using the real-time PCR approach,
      the throughput of samples was considerably increased compared with conventional
      post-PCR readout procedure. Only 7.8% homozygous TAC L3 were found among 102 L3
      which were genotyped from phenotypically BZ-resistant small strongyle
      populations. The percentages of the homozygous TTC and heterozygous TTC/TAC were
      41.3% and 50.9%, respectively. This resulted in a total TAC-allele percentage of
      only 33.3%. These findings correspond to data obtained by genotyping of an
      experimentally selected BZ-resistant cyathostomin population. It is concluded
      that the beta-tubulin codon 200 polymorphism is not the sole mechanism involved
      in the process of BZ resistance in cyathostomins.

PMID- 14653539
TI  - Toxicity of cadmium and zinc to the decaudised cercarial life-span of Diplostomum
      spathaceum (Trematoda: Diplostomidae).
AB  - The toxicity of cadmium and zinc at concentrations ranging from 0.1 to 10000
      microg/l to the life-span of decaudised cercarial bodies (cercariae that have
      shed their tails) of Diplostomum spathaceum was investigated. The effects of
      metal exposure at 3 temperatures (12, 20, and 25 degrees C) and 3 levels of water
      hardness (distilled water, soft water and hard water) were studied. In general,
      under most experimental conditions increasing metal concentrations reduced the
      life-span of decaudised cercariae. Increasing water hardness and decreasing water
      temperature caused an increase in the life-span of both control and metal exposed
      decaudised cercariae. However, at certain isolated metal concentrations,
      associated with a specific level of water hardness and temperature, increased
      survival above controls occurred. Differences in the relative toxicity of cadmium
      and zinc were dependent on the environmental conditions of exposure. The
      decaudised cercarial life-span under metal exposure was found to be generally
      independent of the overall cercarial survival and tail loss in most experimental
      conditions. Prolonged exposure to cadmium and zinc caused changes in the
      decaudised cercarial life-span when compared to individuals decaudised during the
      initial 24 h exposure period to those which were decaudised during the final 24 h
      period of cercarial survival. The validity of studying the decaudised cercarial
      life-span as an indicator of 'fitness' of larvae to migrate through the tissues
      of the target fish host, in terms of glycogen utilization, was assessed for those
      cercariae decaudised during the initial 24 h exposure period only. A limited
      reduction in the decaudised cercarial life-span during this period compared to
      controls was recorded, which may possibly indicate a reduced penetration
      'fitness' of cercariae exposed to cadmium and zinc. The importance and relevance
      of these findings to parasite migration and establishment in the fish host are
      discussed.

PMID- 14653540
TI  - Host immune status affects maturation time in two nematode species--but not as
      predicted by a simple life-history model.
AB  - In theory, the age at which maturation occurs in parasitic nematodes is inversely
      related to pre-maturational mortality rate, and cross-species data on mammalian
      nematodes are consistent with this prediction. Immunity is a major source of
      parasite mortality and parasites stand to gain sizeable fitness benefits through
      short-term adjustments of maturation time in response to variation in immune
      mediated mortality. The effects of thymus-dependent immune responses on
      maturation in the nematode parasites Strongyloides ratti and Nippostrongylus
      brasiliensis were investigated using congenitally thymus-deficient (nude) rats.
      As compared with worms in normal rats, reproductive maturity of parasites
      (presence of eggs in utero) in nude rats occurred later in S. ratti but earlier
      in N. brasiliensis. Immune-mediated differences in maturation time were not
      associated with differences in worm length. Thymus-dependent immunity had no
      effect on prematurational mortality. Results are discussed in relation to
      theoretical expectations and possible explanations for the observed patterns in
      parasite maturation.

PMID- 14653541
TI  - Responsibility for word.

PMID- 14653542
TI  - Women and psychiatric rehabilitation practice.

PMID- 14653543
TI  - Psychosocial rehabilitation service needs of women.

PMID- 14653544
TI  - The passage to adulthood: psychiatric rehabilitation service and transition
      related needs of young adult women with emotional and psychiatric disorders.
AB  - This review addresses the needs and experiences of young adult women, aged 16 to
      21, who have a diagnosis of serious emotional disturbance (SED) or mental
      illness. Given the large numbers of young women with SED, evidence that they are
      underserved, and the continuity of many disorders from adolescence to adulthood,
      an integrative review in this area can enhance our ability to better address
      these young women's needs.

PMID- 14653545
TI  - Achieving the goal of evidence-based psychiatric rehabilitation practices for
      mothers with mental illnesses.
AB  - There is a growing commitment to evidence-based practices in mental health. There
      is no well-articulated evidence base for interventions for mothers with mental
      illnesses. Parenthood is common among women with mental illnesses. Women
      themselves report motherhood is an important role. The risks of parental mental
      illness to children have been demonstrated; the challenges that motherhood brings
      to people with mental illnesses have been described. Because outcomes for both
      children and adults are multiply determined, there are many intervention
      opportunities. Recommendations for intervention are drawn from a focus group
      study and from the existing literature on parent training and support, exemplary
      programs for mothers with mental illnesses, and other evidence-based psychosocial
      interventions. The value of a psychiatric rehabilitation approach is highlighted.
      Challenges in documenting and testing interventions for mothers with mental
      illness include resource allocation and research innovation.

PMID- 14653546
TI  - Family education and support: just for women only?
AB  - Studies of education and support programs for families of adults with mental
      illness' show that the majority of participants are women. In examining why women
      are more likely than men to take part in these programs, this article reviews the
      role of women in caring for an adult with mental illness, with a focus on the
      demands experienced by mothers, sisters, and adult daughters. Given that most
      family education and support program participants are caring for male relatives,
      the differences in the demands of providing care to male versus female relatives
      also are explored. The ways in which education and support programs may be geared
      toward helping women cope with their unique caregiving demands, as well as
      methods to increase the participation of men in these programs, are discussed.

PMID- 14653547
TI  - Gaining insight: who benefits from residential, integrated treatment for people
      with dual diagnoses?
AB  - This retrospective study examines 18-month outcomes for 38 participants in an
      urban, residential integrated treatment (IT) program, and whether residents
      experienced different treatment benefits. Informed by an ACT team approach, the
      program emphasized harm reduction and motivational interventions. The design is
      naturalistic, and outcomes are self-comparisons over time reported in the
      aggregate. Repeated measurements with three standardized scales tracked stage of
      treatment and extent of alcohol and drug use. Outcomes analyses reveal
      advancements in stage of treatment and significant reductions in use of alcohol
      and drugs. Participants also worked more and were hospitalized less.

PMID- 14653548
TI  - A self-rating scale for supported employment participants and practitioners.
AB  - Supported Employment services have significantly enhanced the opportunities for
      competitive employment among persons with mental illnesses. However, the research
      shows that there remain problems with under-utilization and attrition in these
      programs. In addition, the rates of termination among those in supported
      employment placements are high. This article describes a self-rating scale that
      can be used by both employed and unemployed persons that has the potential to
      address these problems. The article also reports a study that shows this self
      rating scale to be a valid, summary index for the employment relevant variables
      of job satisfaction, motivation, and job-related experiences. The self-rating
      scale appears to be a worthy candidate for a trial in supported employment
      operations.

PMID- 14653549
TI  - Supported education programming for adults with psychiatric disabilities: results
      from a national survey.
AB  - Over the last 10 years, supported education (SEd) programs have been the topic of
      many journal publications and conference presentations, but little is known about
      their numbers and types across the U.S. This article reports the results of a
      national survey of all known SEd programs, numbering over 100. The largest number
      was associated with clubhouses, where full and partial SEd models could be
      identified. On-site supported education programs were located in community
      colleges and universities. A dozen "free-standing" programs were also identified.
      Analyses documented differences across program types in services provided, budget
      amounts and sources, and coordination with mental health and higher educational
      institutions. If supported education is to move beyond a specialty program in
      mental health, providers need to do more to market these services and to work
      collaboratively with stakeholder groups to expand supported education
      programming.

PMID- 14653550
TI  - A new measure of coping with symptoms for use with persons diagnosed with severe
      mental illness.
AB  - The purpose of the present investigation was to develop and field test a measure
      of coping with symptoms specifically designed for use with persons diagnosed with
      severe mental illness. Findings are reported on both the development of the
      Coping with Symptoms Checklist and the initial field trial (n = 91) conducted to
      examine reliability and validity. Reliability was assessed by computing
      coefficient alpha, and validity was assessed by examining convergent and
      discriminant correlations (n = 79 for many analyses). Findings suggest that the
      measure is a generally reliable and valid way of assessing how persons diagnosed
      with severe mental illness cope with their symptoms.

PMID- 14653551
TI  - Employing behavioral methods to improve the context of care in a public
      psychiatric hospital: some applications to health care management.
AB  - While intervention procedures grounded in behavioral science have proven useful
      in the provision of direct care and in organizational management, they are seldom
      used effectively in many psychiatric care organizations. Behavioral practitioners
      often acknowledge this fact but few have applied their behavior change skills to
      change the behavior of the organization that is failing. This report outlines
      several examples of how behavioral technology was employed from an administrative
      perspective to encourage and strengthen needed changes in the interdisciplinary
      clinical care procedures of a public psychiatric hospital. The potential of these
      procedures for administering health care provision as well as the challenges
      encountered in realizing such applications are discussed.

PMID- 14653552
TI  - The relationship between staff tenure and client satisfaction in psychosocial
      rehabilitation programs.
AB  - A study conducted at Vinfen, a large Massachusetts-based provider of psychosocial
      rehabilitation services, sheds new light on staff tenure and its relationship to
      participant satisfaction. The researchers surveyed participant satisfaction in
      forty-six residential sites serving people with psychiatric disabilities. The
      study included client and staff demographics. The researchers correlated average
      participant satisfaction score and average staff tenure by program. The results
      of the study did not support the widely held belief that there is a relationship
      between staff tenure and participant satisfaction in residential programs.

PMID- 14653553
TI  - Building the future: psychosocial rehabilitation with a Veterans Construction
      Team.
AB  - The Veterans Construction Team (VCT) is an innovative form of Compensated Work
      Therapy (CWT) for unemployed, homeless veterans who have had a history of
      substance abuse and/or a serious mental or medical illness. The VCT model builds
      social support and self-esteem, while delivering tangible services to public
      entities and providing a relatively high rate of pay and exceptional
      opportunities for skill development. This brief report outlines the VCT model,
      reviews VCTs development and operations, and describes participant reactions.
      Data were collected by interviewing program managers and office staff, field
      supervisors and VCT participants, as well as through archival data on VCT
      projects and VA intake data.

PMID- 14653554
TI  - Open doors.

PMID- 14653555
TI  - Monte Carlo modelling of external radiotherapy photon beams.
AB  - An essential requirement for successful radiation therapy is that the
      discrepancies between dose distributions calculated at the treatment planning
      stage and those delivered to the patient are minimized. An important component in
      the treatment planning process is the accurate calculation of dose distributions.
      The most accurate way to do this is by Monte Carlo calculation of particle
      transport, first in the geometry of the external or internal source followed by
      tracking the transport and energy deposition in the tissues of interest.
      Additionally, Monte Carlo simulations allow one to investigate the influence of
      source components on beams of a particular type and their contaminant particles.
      Since the mid 1990s, there has been an enormous increase in Monte Carlo studies
      dealing specifically with the subject of the present review, i.e., external
      photon beam Monte Carlo calculations, aided by the advent of new codes and fast
      computers. The foundations for this work were laid from the late 1970s until the
      early 1990s. In this paper we will review the progress made in this field over
      the last 25 years. The review will be focused mainly on Monte Carlo modelling of
      linear accelerator treatment heads but sections will also be devoted to
      kilovoltage x-ray units and 60Co teletherapy sources.

PMID- 14653556
TI  - The use of spatially resolved fluorescence and reflectance to determine interface
      depth in layered fluorophore distributions.
AB  - The possibility of using spatially resolved fluorescence and reflectance
      measurements to recover tissue optical properties, fluorophore concentration and
      the thickness of a superficial layer in a two-layer geometry was investigated. A
      diffusion theory model was used to fit reflectance and fluorescence data
      generated using Monte Carlo simulations or experimentally obtained using tissue
      simulating phantoms. Initial analysis fitting diffusion theory generated data
      suggested that it should be possible to recover all parameters from a single set
      of spatially resolved fluorescence and reflectance measurements. However, when
      Monte Carlo or experimental data were fitted the results were less impressive.
      Overall, it was shown that there is a strong coupling between interface depth,
      fluorophore concentration and tissue absorption, especially at larger depths. The
      recovery of all input parameters from a single set of spatially resolved
      measurements was limited to interface depths less than 3 mm, which is a
      reasonable range for measuring fluorophore in skin. When the tissue optical
      properties and fluorophore concentrations were known, then the interface depth
      could be monitored with good accuracy in simulated serial measurements. These
      results may also point to deficiencies in the diffusion theory model that
      introduce significant errors in the fitted results.

PMID- 14653557
TI  - Equivalent physical models and formulation of equivalent source layer in high
      resolution EEG imaging.
AB  - In high-resolution EEG imaging, both equivalent dipole layer (EDL) and equivalent
      charge layer (ECL) assumed to be located just above the cortical surface have
      been proposed as high-resolution imaging modalities or as intermediate steps to
      estimate the epicortical potential. Presented here are the equivalent physical
      models of these two equivalent source layers (ESL) which show that the strength
      of EDL is proportional to the surface potential of the layer when the outside of
      the layer is filled with an insulator, and that the strength of ECL is the normal
      current of the layer when the outside is filled with a perfect conductor. Based
      on these equivalent physical models, closed solutions of ECL and EDL
      corresponding to a dipole enclosed by a spherical layer are given. These results
      provide the theoretical basis of ESL applications in high-resolution EEG mapping.

PMID- 14653558
TI  - Experimental results for 2D magnetic resonance electrical impedance tomography
      (MR-EIT) using magnetic flux density in one direction.
AB  - Magnetic resonance electrical impedance tomography (MR-EIT) is an emerging
      imaging technique that reconstructs conductivity images using magnetic flux
      density measurements acquired employing MRI together with conventional EIT
      measurements. In this study, experimental MR-EIT images from phantoms with
      conducting and insulator objects are presented. The technique is implemented
      using the 0.15 T Middle East Technical University MRI system. The dc current
      method used in magnetic resonance current density imaging is adopted. A
      reconstruction algorithm based on the sensitivity matrix relation between
      conductivity and only one component of magnetic flux distribution is used.
      Therefore, the requirement for object rotation is eliminated. Once the relative
      conductivity distribution is found, it is scaled using the peripheral voltage
      measurements to obtain the absolute conductivity distribution. Images of several
      insulator and conductor objects in saline filled phantoms are reconstructed. The
      L2 norm of relative error in conductivity values is found to be 13%, 17% and 14%
      for three different conductivity distributions.

PMID- 14653559
TI  - A unified noise analysis for iterative image estimation.
AB  - Iterative image estimation methods have been widely used in emission tomography.
      Accurate estimation of the uncertainty of the reconstructed images is essential
      for quantitative applications. While both iteration-based noise analysis and
      fixed-point noise analysis have been developed, current iteration-based results
      are limited to only a few algorithms that have an explicit multiplicative update
      equation and some may not converge to the fixed-point result. This paper presents
      a theoretical noise analysis that is applicable to a wide range of preconditioned
      gradient-type algorithms. Under a certain condition, the proposed method does not
      require an explicit expression of the preconditioner. By deriving the fixed-point
      expression from the iteration-based result, we show that the proposed iteration
      based noise analysis is consistent with fixed-point analysis. Examples in
      emission tomography and transmission tomography are shown. The results are
      validated using Monte Carlo simulations.

PMID- 14653560
TI  - A novel linear programming approach to fluence map optimization for intensity
      modulated radiation therapy treatment planning.
AB  - We present a novel linear programming (LP) based approach for efficiently solving
      the intensity modulated radiation therapy (IMRT) fluence-map optimization (FMO)
      problem to global optimality. Our model overcomes the apparent limitations of a
      linear-programming approach by approximating any convex objective function by a
      piecewise linear convex function. This approach allows us to retain the
      flexibility offered by general convex objective functions, while allowing us to
      formulate the FMO problem as a LP problem. In addition, a novel type of partial
      volume constraint that bounds the tail averages of the differential dose-volume
      histograms of structures is imposed while retaining linearity as an alternative
      approach to improve dose homogeneity in the target volumes, and to attempt to
      spare as many critical structures as possible. The goal of this work is to
      develop a very rapid global optimization approach that finds high quality dose
      distributions. Implementation of this model has demonstrated excellent results.
      We found globally optimal solutions for eight 7-beam head-and-neck cases in less
      than 3 min of computational time on a single processor personal computer without
      the use of partial-volume constraints. Adding such constraints increased the
      running times by a factor of 2-3, but improved the sparing of critical
      structures. All cases demonstrated excellent target coverage (> 95%), target
      homogeneity (< 10% overdosing and < 7% underdosing) and organ sparing using at
      least one of the two models.

PMID- 14653561
TI  - A revision of the gamma-evaluation concept for the comparison of dose
      distributions.
AB  - A method for the quantitative four-dimensional (4D) evaluation of discrete dose
      data based on gradient-dependent local acceptance thresholds is presented. The
      method takes into account the local dose gradients of a reference distribution
      for critical appraisal of misalignment and collimation errors. These contribute
      to the maximum tolerable dose error at each evaluation point to which the local
      dose differences between comparison and reference data are compared. As shown,
      the presented concept is analogous to the gamma-concept of Low et al (1998a Med.
      Phys. 25 656-61) if extended to (3+1) dimensions. The pointwise dose comparisons
      of the reformulated concept are easier to perform and speed up the evaluation
      process considerably, especially for fine-grid evaluations of 3D dose
      distributions. The occurrences of false negative indications due to the discrete
      nature of the data are reduced with the method. The presented method was applied
      to film-measured, clinical data and compared with gamma-evaluations. 4D and 3D
      evaluations were performed. Comparisons prove that 4D evaluations have to be
      given priority, especially if complex treatment situations are verified, e.g.,
      non-coplanar beam configurations.

PMID- 14653562
TI  - First tests of a liquid ionization chamber to monitor intensity modulated
      radiation beams.
AB  - First measurements with a prototype ionization chamber are described to be
      applied in online monitoring of modulated fields in radiation therapy. The
      liquids isooctane, isononane (TMP) and tetramethylsilane (TMS) are used in a high
      purity grade in order to realize high current signals for electronic read-out in
      parallel at frequencies exceeding 10 Hz. Signals of more than a factor 4 with
      respect to isooctane, analysis grade, are obtained. With an electrode structure
      of 400 pads, a uniformity in efficiency within 1.2% has been measured. The
      penumbra of a multileaf collimator could be resolved. Theoretical examination
      verifies that the free electrons in the liquids cause higher signals when the
      measured currents are compared with expectation for ion transport only.

PMID- 14653563
TI  - AI-guided parameter optimization in inverse treatment planning.
AB  - An artificial intelligence (AI)-guided inverse planning system was developed to
      optimize the combination of parameters in the objective function for intensity
      modulated radiation therapy (IMRT). In this system, the empirical knowledge of
      inverse planning was formulated with fuzzy if-then rules, which then guide the
      parameter modification based on the on-line calculated dose. Three kinds of
      parameters (weighting factor, dose specification, and dose prescription) were
      automatically modified using the fuzzy inference system (FIS). The performance of
      the AI-guided inverse planning system (AIGIPS) was examined using the simulated
      and clinical examples. Preliminary results indicate that the expected dose
      distribution was automatically achieved using the AI-guided inverse planning
      system, with the complicated compromising between different parameters
      accomplished by the fuzzy inference technique. The AIGIPS provides a highly
      promising method to replace the current trial-and-error approach.

PMID- 14653564
TI  - Results supporting calculated wall correction factors for cavity chambers.
AB  - Thick walled cavity ionization chambers are used by primary standard laboratories
      as primary air kerma standards in 137Cs and 60Co gamma-rays. Application of the
      cavity theory requires correction for the effects of photon attenuation and
      scattering in the chamber walls. For more than a decade there have been intensive
      discussions about the validity of wall correction factors determined by more
      traditional extrapolation methods versus those calculated by Monte Carlo methods.
      For existing primary standards the alternative methods lead to results that
      differ by up to 50% of the correction itself. This report presents both
      experimental and theoretical results which strongly support the validity of
      calculated wall correction factors. Moreover, it is demonstrated that, in
      selected cases, the application of a linear extrapolation method leads to errors
      in the determination of the air kerma reaching up to 13%.

PMID- 14653565
TI  - Implementation of a practical model for light and heat distribution using laser
      induced thermotherapy near to a large vessel.
AB  - This paper introduces a simulation model for light and heat transport in tissues
      including perfusion effects. The model enables an efficient simulation of the
      damaged zone induced with an optical fibre for laser interstitial thermotherapy
      (LITT). It is designed specially for, but not limited to, tissue ablation in the
      neck region near to vessels. We describe in detail the effects of the rise in
      temperature caused by the absorption of light in tissue, using the heat equation
      and including the cooling effects of flow in vessels and of microperfusion in
      tissue in order to determine the extent of thermal damage. The extent of the
      necrosis zone is calculated with a damage function at each point of a finite
      element method (FEM) mesh. The FEM mesh is implemented with FEMLAB 2.3 as an add
      on for finite element modelling for Matlab 6.5. LITT for tumour ablation in liver
      and some other anatomical regions is a well-known and established method
      (Bundesarztekammer und Kassenarztliche Bundesvereinigung 2002 Assessment der
      Bundesarztekammer und der Kassenarztlichen Bundesvereinigung, Koln).
      Investigations of treatments using LITT in the neck region are still in progress.
      We propose a refined model to validate the LITT method in the future in another
      anatomic region, e.g., in the highly sensitive region of the neck. Our
      calculations show that in order to induce a lesion with a maximum diameter of
      about 1 cm near to a large vessel, an application time between 3 and 4 min is
      needed using a laser power of about 10 W with a Nd:YAG 1064 nm radiation
      wavelength.

PMID- 14653566
TI  - Modelling by percolation theory of the behaviour of natural coral used as bone
      substitute.
AB  - We investigate the relevance of site-bond percolation theory to model the
      resorption and ossification of natural coral implanted in bones. The first step
      of the process is the vascularization of the implant seen here as a percolation
      threshold. The resorption and ossification can thus take place by activation of
      unoccupied sites. We compare our results with previously obtained experimental
      data on implants in porcine cortical bones. Very encouraging results are
      obtained.

PMID- 14653568
TI  - Simple setup for nanosecond time-resolved spectroscopic measurements by a digital
      storage oscilloscope.
AB  - An application of a digital storage oscilloscope for nanosecond time-resolved
      spectroscopic measurements is demonstrated in the range from the single-photon
      region to the multi-photon region. In comparison to the time-correlated single
      photon counting (TCSPC) method, the measurement setup can be greatly simplified
      by averaging the signals measured by the oscilloscope. Moreover, the multi-photon
      events of the fluorescence emissions can be tracked by this simple setup although
      there still exist some disadvantages in the dynamic range of the signal due to
      radio frequency noise, and the temporal response of the photo-multiplier tube.
      This method can simplify time-resolved optical measurements in the nanosecond
      range, such as fluorescence decay and time-of-flight measurements of diffusing
      light. Thus, this simple method will be applicable in many clinical and
      industrial uses.

PMID- 14653567
TI  - A quantitative study of magnetization transfer in MAGIC gels.
AB  - Magnetization transfer (MT) has been measured quantitatively as a function of
      radiation dose in MAGIC polymer gels. The MT rates between the free and immobile
      macromolecular proton pools (kmr and kfm), and the ratio of the sizes of these
      coupled proton pools (Pm/Pf), were measured by analysing the response to an
      inversion recovery sequence. While pm/pf increases linearly with dose, the fast
      MT rate kmf also increases with dose, unlike previous measurements in BANG gels.
      This dependence of kmf on dose suggests there are additional factors that modify
      spin exchange in MAGIC gels as irradiation occurs.

PMID- 14653569
TI  - Computational study of the required dimensions for standard sized phantoms in
      boron neutron capture therapy dosimetry.
AB  - The minimum size of a water phantom used for calibration of an epithermal neutron
      beam of the boron neutron capture therapy (BNCT) facility at the VTT FiR 1
      research reactor is studied by Monte Carlo simulations. The criteria for the size
      of the phantom were established relative to the neutron and photon radiation
      fields present at the thermal neutron fluence maximum in the central beam axis
      (considered as the reference point). At the reference point, for the most
      commonly used beam aperture size at FiR 1 (14 cm diameter), less than 1%
      disturbance of the neutron and gamma radiation fields in a phantom were achieved
      with a minimum a 30 cm x 30 cm cross section of the phantom. For the largest 20
      cm diameter beam aperture size, a minimum 40 cm x 40 cm cross-section of the
      phantom and depth of 20 cm was required to achieve undisturbed radiation field.
      This size can be considered as the minimum requirement for a reference phantom
      for dosimetry at FiR 1. The secondary objective was to determine the phantom
      dimensions for full characterization of the FiR 1 beam in a rectangular water
      phantom. In the water scanning phantom, isodoses down to the 5% level are
      measured for the verifications of the beam model in the dosimetric and treatment
      planning calculations. The dose distribution results without effects caused by
      the limited phantom size were achieved for the maximum aperture diameter (20 cm)
      with a 56 cm x 56 cm x 28 cm rectangular phantom. A similar approach to study the
      required minimum dimensions of the reference and water scanning phantoms can be
      used for epithermal neutron beams at the other BNCT facilities.

PMID- 14653570
TI  - Comments on 'ionization chamber dosimetry of small photon fields: a Monte Carlo
      study on stopping-power ratios for radiosurgery and IMRT beams'.

PMID- 14653571
TI  - In vitro phototoxic properties of triamcinolone 16,17-acetonide and its main
      photoproducts.
AB  - The phototoxicity of triamcinolone 16,17-acetonide has been estimated through a
      panel of in vitro tests. The main target involved in phototoxicity induced by
      triamcinolone appeared to be the cell membrane. Oxygen-independent photohemolysis
      was observed. A photochemical study in water and buffered solutions supported the
      conclusion that this is related to the action of radicals formed upon UV
      irradiation (in particular UV-B) by Norrish Type-I fragmentation of the C-20
      ketone group. Peroxy radicals were formed in the presence of oxygen and were the
      active species in that case. Three photoproducts, isolated from the
      photodegradation of the drug, were submitted to the same toxicity tests. Two of
      them were proved to possess toxic or phototoxic properties on erythrocytes,
      primarily induced by UV-B light, and may participate in the photosensitizing
      activity of triamcinolone 16,17-acetonide. Our in vitro results suggest that the
      drug can elicit weak photosensitizing properties in vivo.

PMID- 14653572
TI  - Localization and photodynamic efficacy of two cationic porphyrins varying in
      charge distributions.
AB  - Two meso-tetraphenylporphyrin derivatives bearing adjacent: 5,10-di[4-(N
      trimethylaminophenyl)-15,20-diphenylporphyrin (DADP-a) or opposite: 5,15-di[4-(N
      trimethylaminophenyl)-10,20-diphenylporphyrin (DADP-o) cationic-N-(CH3)3+ groups
      on two of the para-phenyl positions were examined with regard to photodynamic
      properties as a function of charge distribution. The two adjacent positive
      charges in the DADP-a structure result in a molecular distortion (asymmetry),
      likely from electrostatic repulsion. This could be responsible for the unusual
      interaction of this compound with some solvents and detergent micelles. In
      contrast, DADP-o is a much more symmetric molecule. In a cellular environment,
      fluorescence spectra of the two agents were essentially identical. Subcellular
      localization played a major role in photodynamic efficacy. DADP-a localized in
      mitochondria, and irradiation of photosensitized cells (640-650 nm) resulted in a
      rapid loss of the mitochondrial membrane potential (delta(psi)m), usually a
      prelude to apoptotic cell death. In contrast, DADP-o localized in lysosomes, and
      extensive lysosomal photodamage was observed after irradiation. Both steady-state
      accumulation levels and absorbance spectra favored DADP-o, but the light dose
      required for a 90% cell kill was two-fold greater for DADP-o than for DADP-a, at
      a constant extracellular sensitizer concentration. These data indicate that, on a
      photons/cell basis, DADP-a was five-fold more efficacious. Fluorescence emission
      spectra in different solvents and detergents demonstrated a tendency for DADP-a
      association. We interpret these results to indicate partition of both drugs to
      membrane loci, with mitochondriabeing the more lethal site for photodamage.

PMID- 14653573
TI  - Pothomorphe umbellata extract prevents alpha-tocopherol depletion after UV
      irradiation.
AB  - In this work we evaluated the influence of topical application of P. umbellata
      root extract gel, containing 0.1% of 4-nerolidylcathecol, on the antioxidant
      network in UV-induced oxidative damage in hairless mouse skin. The UV-irradiation
      had no influence on ascorbic acid levels or on the antioxidant enzyme (superoxide
      dismutase, catalase, glutathione reductase and glutathione peroxidase)
      activities, but topical P. umbellata treatment protected alpha-tocopherol from
      being depleted after UV-irradiation. alpha-Tocopherol concentration decreased
      significantly (approximately 40%, P < 0.01) in the irradiated control groups,
      whereas in the P. umbellata-treated group, alpha-tocopherol was totally preserved
      (approximately 100%, P > 0.05). These data demonstrate that P. umbellata may be
      successfully used as a topical photoprotective agent.

PMID- 14653574
TI  - Photoreduction of p-benzoquinones: effects of alcohols and amines on the
      intermediates and reactivities in solutions.
AB  - The photochemistry of 1,4-benzoquinone (BQ) and alkyl-, Cl- and related
      derivatives, e.g. methyl-, 2,6-dimethyl-, chloro-, 2,5-dichloro-1,4-benzoquinone,
      duroquinone and chloranil, was studied in nonaqueous solvents by UV-vis
      spectroscopy using nanosecond laser pulses at 308 nm. The reactivity of the
      triplet state (3Q*) of the quinones with 2-propanol in the absence of water is
      largest for BQ and depends mainly on the quinone structure, whereas the rate
      constant of electron transfer from amines, such as triethylamine (TEA) or 1,4
      diazabicyclo[2.2.2]octane, is close to the diffusion-controlled limit for BQ and
      most derivatives. Photoinduced charge separation after electron transfer from
      amines to 3Q* and the subsequent charge recombination or neutralization are
      supported by time-resolved conductivity measurements. The half-life of the decay
      kinetics of the semiquinone radical (*QH/Q*-) depends significantly on the donor
      and the medium. The photoconversion into the hydroquinones was measured under
      various conditions, the quantum yield, lambda(irr) = 254 nm, increases with
      increasing 2-propanol and TEA concentrations. The effects of quenching of 3Q*,
      the *QH/Q*- radicals and the photoconversion are outlined. The mechanisms of
      photoreduction of quinones in acetonitrile by 2-propanol are compared with those
      by TEA in benzene and acetonitrile, and the specific properties of substitution
      are discussed.

PMID- 14653575
TI  - Interaction of singlet molecular oxygen with melatonin and related indoles.
AB  - Singlet molecular oxygen (1O2) is one of the major agents responsible for
      (photo)oxidative damage in biological systems including human skin and eyes. It
      has been reported that the neural hormone melatonin (MLT) can abrogate 1O2
      mediated cytotoxicity through its purported high antioxidant activity. We studied
      the interaction of MLT with 1O2 in deuterium oxide (D2O), acetonitrile and
      methanol by measuring the phosphorescence lifetime of 1O2 in the presence of MLT
      and related indoles for comparison. Rose bengal (RB) was used as the main 1O2
      photosensitizer. The rate constant (kq) for the total (physical and chemical)
      quenching of 1O2 by MLT was determined to be 4.0 x 10(7) M(-1) s(-1) in D2O (pD
      7), 6.0 x 10(7) M(-1) s(-1) in acetonitrile, and 6.1 x 10(7) M(-1) s(-1) in
      methanol-d1. The related indoles, tryptophan, 5-hydroxyindole, 5
      methoxytryptamine, 5-hydroxytryptamine (5-OH-T, serotonin), 6-hydroxymelatonin (6
      OH-MLT) and 6-chloromelatonin quenched 1O2 phosphorescence with similar kq
      values. We also compared the photosensitized photobleaching rate of MLT with that
      of other indoles, which revealed that MLT is the most sensitive to 1O2 bleaching.
      Hydroxylation of the indole moiety in 5-OH-T and 6-OH-MLT makes them more
      sensitive to photodegradation. In the absence of exogenous photosensitizers MLT
      itself can generate 1O2 with low quantum yield (0.1 in CH3CN) upon UV excitation.
      Thus, the processes we investigated may occur in the skin and eyes during
      physiological circadian rhythm (photo)signaling involving MLT and other indoles.
      Our results indicate that all the indoles studied, including MLT, are quite
      efficient yet very similar 1O2 quenchers. This directly shows that the
      exceptional antioxidant ability proposed for MLT is unsubstantiated when merely
      chemical mechanism(s) are considered in vivo, and it must predominantly involve
      humoral regulation that mobilizes other antioxidant defenses in living organisms.

PMID- 14653576
TI  - Sensitivity of biologically active UV radiation to stratospheric ozone changes:
      effects of action spectrum shape and wavelength ranges.
AB  - Biological action spectra are commonly used to assess health and ecosystem
      responses to increases in spectral ultraviolet (UV) irradiances resulting from
      stratospheric ozone (O3) reductions. For each action spectrum, a normalized
      sensitivity coefficient (the radiation amplification factor [RAF]) can be
      calculated as the relative increase in biologically active UV irradiance for a
      given relative decrease in the atmospheric O3 column amount. We use a detailed
      radiative transfer model to calculate the dependence of RAF on the O3 column
      amount and the solar zenith angle (and, therefore, implicitly on latitude and
      season) for several commonly used action spectra. A simple analytical model is
      used to interpret the results in terms of the semilogarithmic slope of the action
      spectra in the UV-B and UV-A wavelength ranges. We also show that RAF may be
      overestimated substantially if the UV-A portion of an action spectrum is
      significant but is neglected. This is illustrated using several idealized action
      spectra as well as published action spectra for plant responses to UV
      irradiation. Generally, if the portion of an action spectrum measured longward of
      approximately 300 nm spans less than about two orders in magnitude in its
      sensitivity, significant errors in the estimated RAF may ensue, and the use of
      this action spectrum in O3-related studies can be compromised.

PMID- 14653577
TI  - Autofluorescence spectroscopy of normal and malignant human breast cell lines.
AB  - The fluorescence of tryptophan, reduced nicotinamide adenine dinucleotide
      (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) were characterized in
      normal human breast cells as well as in malignant human breast cells of similar
      and dissimilar genetic origins. Fluorescence measurements of each cell line were
      made over a wide range of cell concentrations, and the fluorescence per cell was
      determined from the slope in the linear range of the fluorescence intensity vs
      cell concentration plot. All of the malignant cells showed a statistically
      significant decrease in the tryptophan fluorescence per cell relative to that of
      the normal cells. No statistically significant differences were observed in the
      NAD(P)H or FAD fluorescence per cell between the normal and any of the malignant
      cell types. NAD(P)H fluorescence was also imaged from monolayers of the normal
      and malignant cells (of similar genetic origin) using two-photon fluorescence
      microscopy. A statistically significant decrease in the NAD(P)H fluorescence with
      malignancy was observed, suggesting that fluorescence imaging of single cells or
      the cell monolayer preparation may provide more contrast than volume-averaged
      fluorescence measurements of cells in suspension. In conclusion, the differences
      in normal and malignant human breast tissue fluorescence spectra may be
      attributed in part to differences in the intrinsic cellular fluorescence of
      normal and malignant breast epithelial cells.

PMID- 14653578
TI  - The alkaloid brachycerine is induced by ultraviolet radiation and is a singlet
      oxygen quencher.
AB  - The effects of ultraviolet (UV) radiation on chlorophyll content and accumulation
      of the anti-inflammatory monoterpene-indole alkaloid brachycerine in plants and
      calli of Psychotria brachyceras (Rubiaceae) were investigated. In this study, we
      also investigated a protective role for brachycerine against stress conditions.
      Calli and tip cuttings incubated in nutrient media were daily supplemented with 4
      or 16 h of UV. High-performance liquid chromatography analyses of methanolic
      extracts showed only traces of brachycerine in irradiated aseptic cultures, with
      no alkaloid being observed in control calli. In cuttings, a 10-fold increase in
      brachycerine content was seen after exposure for 16 h to UV-C, whereas a 4 h
      daily supplementation doubled the amount of the alkaloid in leaves. Exposure to a
      UV-B source also doubled the alkaloid yield. In vitro brachycerine was able to
      quench singlet oxygen. The data indicate a potential protective role for
      brachycerine against UV radiation, acting as a UV filter (absorption peaks are
      within the UV range) and a reactive oxygen species scavenger. In addition, UV
      radiation may be used to increase yields of this compound of pharmaceutical
      interest.

PMID- 14653579
TI  - Photochemically modulated endothelial cell thrombogenicity via the thrombomodulin
      tissue factor pathways.
AB  - Photodynamic therapy (PDT) is based on a photochemical reaction using a
      photosensitizer and light to produce reactive oxygen species that have biological
      effects. Although its application in some fields is largely based on thrombosis,
      in the vascular setting thrombosis must be prevented. In this study we examined
      the effects of PDT on the changes in activity of thrombomodulin (TM) and tissue
      factor (TF) as important regulators of the coagulation process of endothelial
      cells. Human umbilical vein endothelial cells were treated with PDT (chloro
      aluminum-sulfonated phthalocyanine, lambda = 630 nm) at different light-energy
      doses, and TM and TF levels were measured using fluorescence spectroscopy.
      Microparticles (MP) were analyzed using flow cytometry analysis. PDT alters the
      thrombogenic state of endothelial cells by causing decreased expression of TM and
      increased expression of functional TF in a light-energy dose-dependent way. PDT
      treated endothelial cells shed large numbers of MP containing high levels of TF.
      TF functionality of PDT-treated cells, measured by a Factor Xa-generating assay,
      was high. TF was located mostly intracellularly and in MP. The disturbed
      anticoagulant balance described in this study may explain the occurrence of
      thrombosis induced by PDT and, if not contained, dispute the suitability of PDT
      as an adjuvant modality to treat vascular restenosis.

PMID- 14653580
TI  - New 5-aminolevulinic acid esters--efficient protoporphyrin precursors for
      photodetection and photodynamic therapy.
AB  - Photodetection (PD) and photodynamic therapy (PDT) with 5-aminolevulinic acid
      (ALA)-induced protoporphyrin IX (PPIX) accumulation are approaches to detect and
      treat dysplasia and early cancer in the gastrointestinal tract and in the urinary
      bladder. Because ALA-induced PPIX production is limited, we synthesized ALA ester
      hydrochlorides 3-22 and tested them in two different in vitro models
      (gastrointestinal tract: HT29-CCD18; urinary bladder: J82-UROTSA). PPIX
      accumulation after incubation with 0.12 mmol/L for 3 h and PPIX accumulation as a
      function of different incubation times were measured using flow cytometry. 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to
      check cellular dark toxicity. Phototoxicity after irradiation was tested. ALA
      nonafluorohexylester hydrochloride 11, ALA thiohexylester hydrochloride 13 and
      ALA dibenzyldiester dihydrochloride 19 induced appreciably increased PPIX levels
      and showed improved phototoxicity compared with the references ALA hydrochloride
      1, ALA hexylester hydrochloride 3 and ALA benzylester hydrochloride 4. Thus, the
      new compounds 11, 13 and 19 are promising compounds for PD and PDT.

PMID- 14653581
TI  - In vitro and in vivo investigations on the photodynamic activity of core-modified
      expanded porphyrin--ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato
      phenyl)-25,27,29-trithia sapphyrin.
AB  - The core modification of expanded porphyrins has been proved to have better
      photochemical properties, which are favorable for photodynamic therapy (PDT)
      applications. In this context, this study was aimed to investigate the in vitro
      and in vivo photodynamic activity of one such core-modified expanded porphyrin,
      namely, ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29
      trithia sapphyrin. For the in vitro studies, human erythrocytes were used as a
      membrane semimodel system to investigate the partitioning ability and drug-uptake
      characteristics. The partition studies on the membrane semimodel system revealed
      that maximum partitioning occurs at 12 microgm/mL concentration, and from the
      drug-uptake studies it is observed that maximum amount of the sensitizer is bound
      to the erythrocyte membranes during a 45 min incubation period. Photohemolysis
      studies at different concentrations of the sensitizer and exposure time showed
      maximum damage at 5 microgm/mL and 30 min exposure time. In vivo studies were
      performed on 7,12-dimethylbenz(a)nthracene-induced superficial squamous cell
      carcinoma on mouse skin. The sensitizer at a concentration of 2.5% in 2.0%
      dimethyl sulfoxide was applied topically on the tumor spot. After 1 h incubation
      the tumor spot was exposed to laser irradiation from Nd-YAG laser at its second
      harmonic wavelength of 532 nm. The photodynamic efficacy was estimated by tumor
      volume measurements at regular intervals after the treatment. One month after PDT
      exposure a 3.9-fold decrease in the tumor volume was observed with respect to the
      tumor volume before treatment. The treatment efficacy was further confirmed by
      histological and fluorescence spectroscopic evaluations of the tissue biopsy
      sample from the treated area. The results of our study suggest that the ammonium
      salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin
      may find possible applications in the new modality of cancer treatment.

PMID- 14653583
TI  - Bacteriorhodopsin analogs from diphenylpolyene chromophores.
AB  - Chromophore-modified bacteriorhodopsin (bR) analogs are prepared, to study the
      nature of chromophore-protein interaction as well as to develop new bR analogs
      that can find applications as photoactive element in molecular electronic
      devices. This article describes the preparation and characterization of hitherto
      unknown bR analogs based on diphenylpolyene chromophores. Diphenylpolyene
      compounds, namely, 4-[(E)-2-phenylvinyl]benzaldehyde (1), 3-methyl-5-[4-[(E)-2
      phenylvinyl]phenyl]penta-2E,4E-dienal (2), 4-[4-phenylbuta-1E,3E
      dienyl]benzaldehyde (3) and 3-methyl-5-[4-[4-phenylbuta-lE,3E-dienyl]phenyl]penta
      2E,4E-dienal (4), have been synthesized, and their interaction with bacterioopsin
      (bOP) has been studied. Whereas aldehydes 2 and 4 interact with bOP and yield bR
      analogs bR-2 and bR-4, aldehydes 1 and 3 do not yield any pigment. Analogs bR-2
      and bR-4 have been characterized for their opsin shift, competitive binding,
      photochemical properties and fluorescence spectral behavior.

PMID- 14653582
TI  - Hyperoxygenation enhances the tumor cell killing of photofrin-mediated
      photodynamic therapy.
AB  - Tumor hypoxia, either preexisting or as a result of oxygen depletion during
      photodynamic therapy (PDT) light irradiation, can significantly reduce the
      effectiveness of PDT-induced cell killing. To overcome tumor hypoxia and improve
      tumor cell killing, we propose using supplemental hyperoxygenation during
      Photofrin-PDT. The mechanism for the tumor cure enhancement of the
      hyperoxygenation-PDT combination is investigated using an in vivo-in vitro
      technique. A hypoxic tumor model was established by implanting mammary
      adenocarcinoma in the hind legs of mice. Light irradiation (200 J/cm2 at either
      75 or 150 mW/cm2), under various oxygen supplemental conditions (room air,
      carbogen, 100% normobaric or hyperbaric oxygen), was delivered to animals that
      received 12.5 mg/kg Photofrin 24 h before light irradiation. Tumors were
      harvested at various time points after PDT and grown in vitro for colony
      formation analysis. Treated tumors were also analyzed histologically. The results
      show that when PDT is combined with hyperoxygenation, the hypoxic condition could
      be improved and the cell killing rate at various time points after PDT could be
      significantly enhanced over that without hyperoxygenation, suggesting an enhanced
      direct and indirect cell killing associated with high-concentration oxygen
      breathing. This study further confirms our earlier observation that when a PDT
      treatment is combined with hyperoxygenation it can be more effective in
      controlling hypoxic tumors.

PMID- 14653584
TI  - Interaction of Natronobacterium pharaonis phoborhodopsin (sensory rhodopsin II)
      with its cognate transducer probed by increase in the thermal stability.
AB  - Pharaonis phoborhodopsin (ppR, also called Natronobacterium pharaonis sensory
      rhodopsin II) and its transducer protein, pharaonis halobacterial transducer of
      ppR (pHtrII), form a signaling complex, and light signals are transmitted from
      the sensor to the transducer by the protein-protein interaction. A truncated
      pHtrII(1-159) consisting of intramembrane helices (expressing amino acid residues
      from the first to the 159th position) and ppR form the complex in a solution
      containing 0.1% n-dodecyl-beta-D-maltoside. At 75-85 degrees C, the time
      dependent color loss of ppR was caused by denaturation. We found that pHtrII(1
      159) retarded the denaturation rate of ppR. This increase in the thermal
      stability was used as a probe for the binding ability in the dark. Tyr199 of ppR
      and Asn74 of pHtrII(1-114) were proposed as amino acid residues interacting with
      each other through hydrogen bonding. Then,ppR and pHtrII(1-159) mutants at these
      positions were prepared to examine the effect on the binding in the dark. The
      wild-type and Y199F mutant can bind pHtrII(1-159), suggesting that the hydrogen
      bonding between these specific amino acid residues may not be the only cause of
      the binding, but the hydrophobic interaction via phenyl ring of ppR may
      contribute dominantly.

PMID- 14653585
TI  - Organotypic raft cultures as an effective in vitro tool for understanding Raman
      spectral analysis of tissue.
AB  - There is a growing body of evidence showing that optical spectroscopy has the
      potential to be a useful in vivo diagnostic tool. Yet, so far there is no
      definitive cellular and biochemical understanding for the differences seen in the
      spectra from different tissue categories and disease states. In this study, we
      examine the use of organotypic raft cultures as an in vitro model of in vivo
      tissue conditions in an attempt to overcome some of the limitations of previously
      used methods. Organotypic raft cultures resembling normal and dysplastic
      epithelial cervical tissue were constructed and grown at an air-liquid interface
      for 2 weeks. Raman spectra of normal as well as dysplastic raft cultures were
      measured and compared with in vivo spectra from the corresponding tissue type.
      Histologic comparisons ensured that the raft cultures had similar structure and
      morphology to the corresponding intact tissue types. Raman spectra were also
      acquired from different layers of tissue. Spectral comparisons show that the
      Raman spectra of the raft cultures are similar to the spectra acquired from the
      cervix in vivo for both normal and dysplastic tissues. These results show that
      organotypic raft cultures are an effective and useful tool for the cellular and
      biochemical analysis of tissue spectroscopy.

PMID- 14653586
TI  - Dipole strengths of the Qy(0,0) bacteriochlorophyll c transition.
AB  - The absorption spectra of bacteriochlorophyll (BChl) c solutions in two mixtures
      of two solvents (acetonitrile with pyridine and dimethylsulfoxide with methanol)
      exhibiting different refractive indices were measured and deconvoluted into
      Gaussian components. The refractive index of mixed solvents was changed by the
      change in the ratio of the volumes of the liquids used in the mixture. Using the
      Qy(0,0) band half widths and absorption coefficient, based on the simplified
      formula proposed by Knox, the dipole strengths of the Qy(0,0) BChl c transition
      for various values of solvent refractive index were calculated and compared with
      values given by Knox and Spring. For both investigated combinations of two
      liquids, the dependence of Qy(0,0) transition dipole strength of the BChl c on
      solvent refractive index was almost linear. The slopes of the lines obtained from
      the experimental absorption bands were different for two investigated solvent
      mixtures. More accurate linear dependence and similar slopes of lines for both
      solvent mixtures were obtained using half widths and absorption coefficients of
      the Gaussian components of Qy(0,0) transition. It is explained by the
      superposition of the contributions from other electronic and vibronic transitions
      of BChl c monomers or possibly also from transitions of the pigments involved in
      some complexes with solvent molecules in the absorption region investigated. The
      results show that the formula proposed by Knox can be successfully applied also
      for BChl c, after elimination of the overlapped contributions from the other
      transitions, by applying Gaussian analysis to select only contribution from
      Qy(0,0) pigment transition.

PMID- 14653587
TI  - Health economics and the orthopaedic surgeon.

PMID- 14653588
TI  - Complex regional pain syndrome.

PMID- 14653589
TI  - The influence of immediate surgical treatment of proximal femoral fractures on
      mortality and quality of life. Operation within six hours of the fracture versus
      later than six hours.
AB  - We compared the mortality and outcome of 182 patients with proximal fractures of
      the femur after immediate and delayed surgical treatment. Seventy-nine patients
      were operated upon within six hours of the fracture (group 1) and 103 patients
      were operated upon after this period of time (group 2). At six months follow-up,
      group 1 had a significantly lower mortality rate. There was a good outcome in
      both groups with no differences in the outcome. Neither surgical nor anaesthetic
      factors appeared to have influenced mortality. The subdivision of groups revealed
      that patients operated on within 24 hours had a better outcome than those whose
      surgery was delayed. Although there may have been a bias, as patients were not
      randomly assigned to immediate or delayed surgical treatment, the data suggest
      that early stabilisation may be associated with a lower mortality rate. Even with
      pre-clinical delays of more than six hours early treatment should still be
      attempted, as better results seem to be achieved after 24 hours compared to a
      later time in our patients.

PMID- 14653590
TI  - Acetabular revision in total hip replacement with a press-fit cup.
AB  - The need for supplementary screw fixation in acetabular revisions is still widely
      debated. We carried out 439 acetabular revisions over an eight-year period. In
      171 hips with contained or small segmental defects, the Morscher press-fit cup
      was used. These revisions were followed prospectively. No screws were used for
      additional fixation. A total of 123 hips with a mean follow-up of 7.4 years (5 to
      10.5) were available for clinical and radiological review. There was no further
      revision of a press-fit cup for aseptic loosening. Radiological assessment
      revealed osteolysis in three hips. Of the original 171 hips there was cranial and
      medial migration of up to 6 mm at two years in 44 (26%). No further migration was
      seen after the second post-operative year. Acetabular revision without screws is
      possible with excellent medium-term results in well selected patients.

PMID- 14653591
TI  - The extensile rectus snip exposure in revision of total knee arthroplasty.
AB  - Revision of a total knee arthroplasty may require an extensile approach to permit
      a satisfactory exposure without compromising the attachment of the patellar
      tendon. It has been assumed that a rectus snip is a relatively benign form of
      release, but the effect of using this approach on function, pain and patient
      satisfaction is not known. From January 1997 to December 1999, 107 patients who
      underwent revision of total knee arthroplasty were followed up at a minimum of
      two years (mean 40.5 months) and assessed by the Oxford Hip Score, the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Short-Form
      (SF)-12 and patient satisfaction. Co-morbidity, surgical exposure, the Hospital
      for Special Surgery (HSS) knee scores and the range of movement were also used. A
      standard medial parapatellar approach was used in 57 patients and the rectus snip
      in 50. The two groups were equivalent for age, sex and co-morbidity scores. The
      WOMAC function, pain, stiffness and satisfaction scores demonstrated no
      statistical difference. The use of a rectus snip as an extensile procedure has no
      effect on outcome.

PMID- 14653592
TI  - Fixation of a hydroxyapatite-tricalcium phosphate-coated cementless knee
      prosthesis. Clinical and radiographic evaluation seven years after surgery.
AB  - Miller-Galante II total knee arthroplasty (MG II TKA) was performed on 32 knees
      in 30 patients. On both the femoral and tibial components, the fibre-metal area
      was plasma-sprayed with hydroxyapatite-tricalcium phosphate (HA-TCP). The
      clinical and radiographic outcome was evaluated. A mean preoperative knee score
      of 26.0 +/- 18.6 (SD) increased to 97.5 +/- 3.5 and a mean pre-operative
      functional score of 21.7 +/- 15.0 (SD) increased to 83.4 +/- 12.4 at follow-up of
      seven years. Clear zones were common around the components at one month post
      operatively but had completely disappeared after six months. An autopsy of a
      patient who underwent MG II TKA with HA-TCP two years previously, showed
      osteogenesis in all parts of the fibre-metal, and bone tissue comprised 77.7% of
      the interface. This coated prosthesis has good early fixation which is maintained
      at seven years with good clinical and radiographic outcomes.

PMID- 14653593
TI  - A modified system of stress radiography for patellofemoral instability.
AB  - Axial radiographs were obtained under valgus and external rotation stress at 45
      degrees of knee flexion with and without contraction of the quadriceps muscle in
      order to assess the dynamics of patellar subluxation or dislocation. The
      radiography was performed on 82 knees in 61 patients with patellofemoral
      instability, and on 44 normal knees. The lateral patellofemoral angle and the
      congruence angle were measured and compared with the conventional Merchant views.
      Both parameters showed greater differences between symptomatic and normal knees
      on the stress radiographs obtained without quadriceps contraction. There was a
      major difference in the lateral patellofemoral angles between the groups, which
      clearly distinguished symptomatic knees from normal controls. Congruence angles
      on stress radiography had a significant correlation with the functional scores
      obtained after a period of conservative treatment and a positive correlation with
      the frequency of patellar subluxation. When the quadriceps contracted, two
      patterns of patellar shift were observed. While the patella reduced into the
      trochlear groove in all normal knees and about 70% of the symptomatic knees,
      contraction of the quadriceps caused further subluxation of the patella in the
      remaining symptomatic knees. All the knee joints which showed this displacement
      failed to respond to conservative treatment and eventually required surgical
      treatment. Thus, this technique of stress radiography is a simple, cost-effective
      and useful method of evaluating patellar instability and predicting the
      prognosis.

PMID- 14653594
TI  - The peroneus quartus muscle. Anatomy and clinical relevance.
AB  - Whilst a few studies have associated various symptoms with the presence of a
      peroneus quartus muscle in the peroneal compartment of the leg, little is known
      of the clinical relevance of this muscle. We dissected 102 cadaver legs and
      reviewed the magnetic resonance images of 80 patients with symptoms from the
      ankle. The peroneus quartus, with a number of different attachments, was present
      in 6.6% of the legs. It most commonly arose from the peroneus brevis muscle and
      inserted into the retrotrochlear eminence of the calcaneum. Associated pathology
      included a longitudinal tear in the tendon of peroneus brevis, possible peroneal
      tendon subluxation or dislocation, and a prominent retrotrochlear eminence. On
      the MR scans its presence was associated with pain and weakness of the ankle.
      Orthopaedic surgeons and radiologists should be aware of the possible presence of
      the peroneus quartus muscle, not only because of possible associated pathology,
      but also for its potential use for surgical reconstruction.

PMID- 14653595
TI  - Arthroplasty of the elbow in haemophilia.
AB  - Total elbow replacement can be a valuable option for the treatment of the elbow
      in haemophilia where there are associated arthropathic changes. We describe the
      outcome of seven elbow replacements in five consecutive patients with severe
      haemophilia A (native factor levels < 1%) at a mean of 42 months (25 to 65) after
      operation. All the patients had excellent relief of pain and improvement in
      function. One failure was due to infection in an immunocompromised patient with
      both HIV and Hepatitis C antibodies who was on anti-retroviral chemotherapy. The
      implant was revised at 30 months in a one-stage procedure and showed no evidence
      of loosening or infection 35 months later.

PMID- 14653596
TI  - Levator scapulae and rhomboid transfer for paralysis of trapezius. The Eden-Lange
      procedure.
AB  - Spinal accessory nerve palsy leads to painful disability of the shoulder,
      carrying an uncertain prognosis. We reviewed the long-term outcome in 16 patients
      who were treated for pain, weakness of active elevation and asymmetry of the
      shoulder and the neck due to chronic paralysis of the trapezius muscle, as a
      result of nerve palsy. Of four patients who were treated conservatively, none
      regained satisfactory function, although two became pain-free. The other 12
      patients were treated operatively with transfer of the levator scapulae to the
      acromion and the rhomboid muscles to the infraspinatus fossa (the Eden-Lange
      procedure). At a mean follow-up of 32 years, the clinical outcome of the
      operatively treated patients was excellent in nine, fair in two, and poor in one
      patient, as determined by the Constant score. Pain was adequately relieved in 11
      and overhead function was restored in nine patients. Pre-operative
      electromyography had been carried out in four patients. In two, who eventually
      had a poor outcome, a concomitant long thoracic and dorsal scapular nerve lesion
      had been present. The Eden-Lange procedure gives very satisfactory long-term
      results for the treatment of isolated paralysis of trapezius. In the presence of
      an additional serratus anterior palsy or weak rhomboid muscles, the procedure is
      less successful in restoring shoulder function.

PMID- 14653597
TI  - Surgical treatment of lumbar disc herniation in elderly patients.
AB  - Between 1995 and 1999, 12 patients aged 65 years or more (mean 70.2) with lumbar
      disc herniation, underwent partial laminectomy and nucleotomy. The results were
      compared with those of 25 younger patients aged between 20 and 40 years (mean
      30.1), who underwent the same surgical procedure. The Japanese Orthopedic
      Association (JOA) score was used to assess the clinical outcome. The minimum
      follow-up was 12 months. The pre- and post-operative total JOA scores and the
      rate of improvement of the JOA score were not significantly different between the
      elderly (11.1, 24.3 points, and 74.1%), and the younger group (11.6, 26.4 points
      and 84.5%). The results of this study indicate that the outcome of lumbar
      discectomy in elderly patients is as good as in younger patients.

PMID- 14653598
TI  - High-sensitivity analysis of serum C-reactive protein in young patients with
      lumbar disc herniation.
AB  - We measured the serum concentration of C-reactive protein (CRP) by a high
      sensitive method in patients with lumbar disc herniation. There were 48 patients
      in the study group and 53 normal controls. The level and type of herniation were
      evaluated. The clinical data including the neurological findings, the angle of
      straight leg raising and post-operative recovery as measured by the Japanese
      Orthopaedic Association (JOA) score, were recorded. The high-sensitive CRP (hs
      CRP) was measured by an ultrasensitive latex-enhanced immunoassay. The mean hs
      CRP concentration was 0.056 +/- 0.076 mg/dl in the patient group and 0.017 +/-
      0.021 mg/dl in the control group. The difference was statistically significant (p
      = 0.006). There was no other correlation between the hs-CRP concentration and the
      level and type of herniation, or the pre-operative clinical data. A positive
      correlation was found between the concentration of hs-CRP before operation and
      the JOA score after. Those with a higher concentration of hs-CRP before operation
      showed a poorer recovery after. The significantly high concentration of serum hs
      CRP might indicate a systemic inflammatory response to impingement of the nerve
      root caused by disc herniation and might be a predictor of recovery after
      operation.

PMID- 14653599
TI  - Separate vertical wiring for the fixation of comminuted fractures of the inferior
      pole of the patella.
AB  - Comminuted and displaced fractures of the inferiorole of the patella are not easy
      to reduce and it is difficult to fix the fragments soundly enough to allow early
      movement of the knee. We have evaluated the clinical effectiveness of the
      separate vertical wiring technique in acute comminuted fractures of the inferior
      pole of the patella. A biomechanical study was also performed using ten pairs of
      embalmed cadaver knees. A four-part fracture was made on the inferior pole of the
      patella and fixed by two separate vertical wires on one side and two pull-out
      sutures after partial patellectomy on the other. The ultimate load to failure in
      the first group was significantly higher than in the second (250.1+/- 109.7 N v
      69.7 +/- 18.9 N, p < 0.002), as was the stiffness (279.9 +/- 76.4 N/mm v 23.2 +/-
      11.4 N/mm, p < 0.001). The separate wire technique was used in 25 patients with
      comminuted fractures of the inferior pole of the patella who were followed up for
      a mean period of 22 months (10 to 50). All the fractures healed at a mean of
      seven weeks (6 to 10). No breakage of a wire or infection occurred. The mean
      grading at the final follow-up was 29.5 points (27 to 30) using the Bostman
      method. This technique preserved the length of the patella, fixed the comminuted
      fragments of the inferior pole and avoided long-term immobilisation of the knee.

PMID- 14653600
TI  - Surgical treatment of symptomatic osteochondroma. A three- to eight-year follow
      up study.
AB  - Our aim was to investigate the outcome of excision ofosteochondromas. Between
      1994 and 1998, 92 symptomatic osteochondromas in 86 patients were excised. There
      were 40 women and 46 men with a mean age of 20 years (3 to 62). Of these, 56 had
      a solitary osteochondroma and 30 had multiple hereditary tumours. The presenting
      symptoms were pain (79.1%), swelling (23.3%), reduced range of movement (19.8%),
      cosmetic abnormalities (17.4%), and bursitis (12.8%). The most common site
      (37.6%) was around the knee. Four patients had major complications (4.7%)
      including one intra-operative fracture of the femoral neck and three nerve
      palsies which resolved after decompression. Six patients had minor complications.
      Overall, 93.4% of the preoperative symptoms resolved after excision of the
      tumours. Excision is a successful form of treatment for symptomatic
      osteochondromas with a low morbidity.

PMID- 14653601
TI  - Outcome after later combined brachial plexus and shoulder surgery after birth
      trauma.
AB  - Of 22 infants aged between 11 and 29 months who underwent a combined
      reconstruction of the upper brachial plexus and shoulder for the sequelae of a
      birth injury, 19 were followed up for two or more years. The results were
      evaluated using a modified Gilbert scale. Three patients required a secondary
      procedure before follow-up. Three patients had a persistent minor internal
      rotation contracture. All improved by at least two grades on a modified Gilbert
      scale.

PMID- 14653602
TI  - Closed reduction and percutaneous fixation of supracondylar fracture of the
      humerus and ipsilateral fracture of the forearm in children.
AB  - We treated 22 children with a supracondylar fracture of the humerus and an
      ipsilateral fracture of the forearm by closed reduction and percutaneous
      fixation. There were four Gartland type-II and 18 Gartland type-III supracondylar
      fractures of the humerus. There were fractures of both bones of the forearm in 16
      and of the radius in six. Both the supracondylar and the distal forearm fractures
      were treated by closed reduction and percutaneous fixation. The mean follow-up
      time was 38.6 months. At the latest follow-up there were 21 excellent or good
      results and one fair result. There were no cases of delayed union, nonunion or
      malunion. Five nerve injuries were diagnosed on admission and all recovered
      spontaneously within eight weeks. No patient developed a compartment syndrome.

PMID- 14653603
TI  - Closed reduction of developmental dislocation of the hip by prolonged traction.
AB  - The efficacy of traction before an attempted closed reduction for patients with
      developmental dislocation of the hip remains controversial. We treated 55
      children (62 dislocations of the hip) by preliminary, prolonged traction for a
      mean of eight weeks. All were followed up for at least two years in order to
      observe the development of any avascular changes within the femoral head. Of the
      55 children, 27 (31 dislocations) were followed up until they were over six years
      of age. Fifty-seven of the 62 hips (92%) showed a successful closed reduction.
      Only one had radiological evidence of avascular necrosis of the femoral head. Of
      the 31 hips which were followed up to over six years of age, 15 (48%) showed
      residual subluxation. Our method of prolonged preliminary traction leads to a
      high rate of successful closed reduction, a low incidence of avascular necrosis
      and a reduced need for secondary operations.

PMID- 14653604
TI  - Compression of the sciatic nerve by wear debris following total hip replacement:
      a report of three cases.
AB  - Pain in the distribution of the sciatic nerve is common in the elderly. In the
      presence of a long-standing joint replacement, consideration should be given as
      to whether compression might be due to an extraspinal cause. We present three
      women, in whom a mass of wear debris from a previous total hip replacement caused
      compression of the sciatic nerve posterior to the hip. The symptoms were relieved
      immediately following operation.

PMID- 14653605
TI  - Acid-etched microtexture for enhancement of bone growth into porous-coated
      implants.
AB  - We designed an in vivo study to determine if the superimposition of a
      microtexture on the surface of sintered titanium beads affected the extent of
      bone ingrowth. Cylindrical titanium intramedullary implants were coated with
      titanium beads to form a porous finish using commercial sintering techniques. A
      control group of implants was left in the as-sintered condition. The test group
      was etched in a boiling acidic solution to create an irregular surface over the
      entire porous coating. Six experimental dogs underwent simultaneous bilateral
      femoral intramedullary implantation of a control implant and an acid etched
      implant. At 12 weeks, the implants were harvested in situ and the femora
      processed for undecalcified, histological examination. Eight transverse serial
      sections for each implant were analysed by backscattered electron microscopy and
      the extent of bone ingrowth was quantified by computer-aided image analysis. The
      extent of bone ingrowth into the control implants was 15.8% while the extent of
      bone ingrowth into the etched implants was 25.3%, a difference of 60% that was
      statistically significant. These results are consistent with other research that
      documents the positive effect of microtextured surfaces on bone formation at an
      implant surface. The acid etching process developed for this study represents a
      simple method for enhancing the potential of commonly available porous coatings
      for biological fixation.

PMID- 14653606
TI  - Expression of CCAAT/enhancer-binding protein-beta (C/EBPbeta) and CHOP in the
      murine growth plate. Two possible key modulators of chondrocyte differentiation.
AB  - Our aim was to evaluate the expression of transcription factors CCAAT/enhancer
      binding protein-beta (C/EBPbeta) and C/EBP-homologous protein (CHOP) in the
      growth plate. Proximal tibial epiphyseal growth plates from ten 15-day-old Wistar
      rats were used. Additionally, anti-proliferating cell nuclear antigen (PCNA),
      anti-5-bromo-2'-deoxyuridine (BrdU) immunostaining, terminal transferase dUTP
      nick end-labelling (TUNEL) and nucleolar organiser region-associated proteins
      (AgNOR) techniques were peformed. The histological morphology of the growth plate
      from C/EBPbeta knock-out mice was also analysed. The normal growth plate showed
      that C/EBPbeta and CHOP factors are expressed both in the germinative/ upper
      proliferative and in the lower proliferative zones. Furthermore, BdrU+ and PCNA+
      cells were present exclusively in the germinative and proliferative zones, while
      TUNEL+ and AgNOR+ cells were seen in all three zones of the growth plate.
      Acellular areas, hypocellularity, the increase in cell death and anomalies in the
      architecture of the cell columns were observed in the growth plates of C/EBPbeta
      (-/-) knockout mice. We suggest that C/EBPbeta and CHOP transcription factors may
      be key modulators participating in the chondrocyte differentiation process in the
      growth plate.

PMID- 14653607
TI  - Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip
      replacement.
AB  - In the differentiation of osteoclasts the differentiation factor (RANKL)
      interacts with the receptor activator of NF-kappaB (RANK) in a direct cell-to
      cell contact between osteoblast and (pre)osteoclast. This is inhibited by soluble
      osteoprotegerin (OPG). The mRNA levels of both RANKL (p < 0.01) and RANK (p <
      0.05) were high in peri-implant tissue and RANKL+ and RANK+ cells were found in
      such tissue. Double labelling also disclosed soluble RANKL bound to RANK+ cells.
      We were unable to stimulate fibroblasts to express RANKL in vitro, but monocyte
      activation with LPS gave a fivefold increase in RANK mRNA levels. In contrast to
      RANKL and RANK expression in peri-implant tissue, expression of OPG was
      restricted to vascular endothelium. Endothelial cell OPG mRNA levels were
      regulated by TNF-alpha and VEGF, but not by hypoxia. It is concluded that
      activated cells in the interface tissue overproduce both RANKL and RANK and they
      can interact without interference by OPG.

PMID- 14653608
TI  - Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic
      osteolysis.
AB  - We investigated the circulating levels of the main cytokines involved in bone
      resorption (IL-1beta, IL-6, TNF-alpha), prostaglandins (PGE2) and
      metalloproteases (MMP-1), as possible early markers of osteolysis, in the serum
      of eight patients with periprosthetic osteolysis and ten patients without
      osteolysis. All had received a cementless hip prosthesis (ABG-1). We also
      assessed the serum levels of IL-1 and TGF-beta anti-inflammatory cytokines
      exerting protective effect on bone resorption. The mean serum levels of IL-1beta,
      IL-6, TNF-alpha, TGF-beta, MMP-1, and PGE2 in patients with periprosthetic
      osteolysis did not differ significantly from those of patients without osteolysis
      or from those of normal controls. IL-11 serum levels were not detectable at all
      in any of the patients, while they were detected within normal reference values
      in the control subjects (significant inverse correlation). We believe that
      circulating cytokines cannot be regarded as markers of osteolysis, a condition
      characterised by a local inflammation without systemic signs of inflammation. On
      the contrary, the undetectable levels of IL-11 in implanted patients could
      provide evidence for a lack of balance between pro- and anti-inflammatory
      cytokines in these patients.

PMID- 14653609
TI  - Pain related to the psoas muscle after total hip replacement.

PMID- 14653610
TI  - A ten-to-15 year follow-up of the Cementless Spotorno stem.

PMID- 14653611
TI  - The effect of knee flexion on the popliteal artery and its surgical significance.

PMID- 14653612
TI  - Impingement syndrome associated with whiplash injury.

PMID- 14653613
TI  - The provision of services for spinal disorders.

PMID- 14653615
TI  - Staging and preparation of human fetal striatal tissue for neural transplantation
      in Huntington's disease.
AB  - Transplantation of human fetal central nervous system tissue has been shown to be
      of benefit in Parkinson's disease, and is currently being explored as a
      therapeutic option in Huntington's disease. The success of a neural transplant is
      dependent on a number of factors, including the requirement that donor cells are
      harvested within a given developmental window and that the cell preparation
      protocols take account of the biological parameters identified in animal models.
      Although many of the criteria necessary for a successful neural transplant have
      been defined in animal models, ultimately they must be validated in human
      studies, and some issues can only ever be addressed in human studies.
      Furthermore, because neural transplantation of human fetal tissue is limited to
      small numbers of patients in any one surgical center, largely due to practical
      constraints, it is crucial that tissue preparation protocols are clearly defined
      and reproducible, so that (i) multicenter trials are possible and are based on
      consistent tissue preparation parameters, and (ii) results between centers can be
      meaningfully analyzed. Here we describe the preparation of human fetal striatum
      for neural transplantation in Huntington's disease, and report on the validation
      of a method for estimating the developmental stage of the fetus based on direct
      morphometric measurements of the embryonic tissue.

PMID- 14653617
TI  - Evaluation of an MRI-based protocol for cell implantation in four patients with
      Huntington's disease.
AB  - The purpose of this study was to evaluate our surgical protocol for the
      preparation and delivery of suspensions of fetal tissue into the diseased human
      brain. We implanted suspensions of human fetal striatal anlage into the right
      caudate and putamen of four patients with Huntington's disease. Postoperative 3
      tesla MR imaging confirmed accurate graft placement. Variability in graft
      survival was noted and the MR signal changes over 6 months revealed persistent
      hyperintense signal on T2-weighted images. Our results are consistent with those
      described by other groups and indicate that our surgical protocol is safe,
      accurate, and reproducible.

PMID- 14653616
TI  - Long-term hibernation of human fetal striatal tissue does not adversely affect
      its differentiation in vitro or graft survival: implications for clinical trials
      in Huntington's disease.
AB  - Transplantation of human fetal CNS tissue is a promising therapy for
      neurodegenerative conditions such as Huntington's disease (HD), but its
      widespread adoption is limited by restricted tissue availability. One method of
      overcoming this problem would be to store the tissue in hibernation medium, an
      approach that we reported previously for human fetal striatal tissue stored for
      up to 24 h. We now demonstrate the feasibility of storing such tissue for up to 8
      days in hibernation medium. When either fresh or 8-day hibernated striatal cells
      were cultured under standard conditions for 4 days, the proportion of DARPP-32
      positive neurons did not differ significantly, although the total number of cells
      was significantly less from tissue that had been hibernated. Six weeks after
      transplantation into cyclosporin A-immunosuppressed unilateral quinolinic acid
      lesioned rats, there was no significant difference between fresh and hibernated
      grafts, both in terms of graft volume and extent of striatal phenotypic markers.
      This study therefore clearly demonstrates that hibernation of human fetal
      striatal tissue for up to 8 days is not deleterious to its differentiation in
      culture or survival following transplantation, and is therefore an appropriate
      method of storage for this tissue.

PMID- 14653618
TI  - The influence of donor age, nerve growth factor, and cografting with drosophila
      cells on survival of peripherally grafted embryonic or fetal rat dorsal root
      ganglia.
AB  - Previous studies have shown that embryonic rat and human dorsal root ganglion
      (DRG) cells survive grafting to the cavity of extirpated adult rat DRG.
      Furthermore, grafted human embryonic neurons were shown to send axons
      peripherally and into the spinal cord, where they establish functional synaptic
      connections. This study analyzed the survival of orthotopically allografted rat
      DRG cells from embryonic stages 15 (E15) and 20 (E20), and the influence on their
      survival of nerve growth factor (NGF). NGF was delivered to the DRG transplants
      either by pump infusion or by cotransplantation of cells from Drosophila
      melanogaster, transgenic for human NGF. Lumbar DRGs of adult rats were removed
      and a collection of E15 or E20 DRGs placed in the cavity. One month after
      grafting the total number of DRG cells in the grafts was counted. Differentiation
      of subpopulations of DRG cells was estimated by counting cells immunostained for
      calcitonin gene-related peptide (CGRP), Griffonia simplicifolia agglutinin
      isolectin B4 (GSA), or heavy neurofilament protein (antibody RT97). The results
      show: i) similar survival of E15 and E20 grafts, with great variability in the
      survival of different subpopulations in E15 transplants, but a more consistent
      distribution of different phenotypes in E20 transplants; ii) infusion of NGF for
      2 weeks increases the survival of E15 transplants, but has a negative effect on
      E20 transplants; iii) Drosophila cells transfected with human NGF gene survive
      peripheral xenografting and have a positive effect on the survival of the GSA-
      and CGRP-positive populations in E15 and E20 transplants; iv) Drosophila cells
      without the human NGF gene increase cell survival in E20 transplants. These data
      suggest that i) the effect of NGF is dependent on the embryonic stage of the
      transplants, ii) age-dependent sensitivity to NGF influences graft survival, and
      iii) transgenic Drosophila cells can be cotransplanted with embryonic neural
      tissue to the mammalian peripheral nervous system with a positive effect on the
      survival of neural grafts.

PMID- 14653619
TI  - Generation of 3D retina-like structures from a human retinal cell line in a NASA
      bioreactor.
AB  - Replacement of damaged cells is a promising approach for treatment of age-related
      macular degeneration (AMD) and retinitis pigmentosa (RP); however, availability
      of donor tissue for transplantation remains a major obstacle. Key factors for
      successful engineering of a tissue include the identification of a neural cell
      line that is: homogeneous but can be expanded to give rise to multiple cells
      types; is nontumorigenic, yet capable of secreting neurotrophic factors; and is
      able to form three-dimensional (3D), differentiated structures. The goal of this
      study was to test the feasibility of tissue engineering from a multipotential
      human retinal cell line using a NASA-developed bioreactor. A multipotential human
      retinal precursor cell line was used to generate 3D structures. In addition,
      retinal pigment epithelium (RPE) cells were cocultured with neural cells to
      determine if 3D retinal structures could be generated in the bioreactor with
      cells grown on laminin-coated cytodex 3 beads. Cell growth, morphology, and
      differentiation were monitored by light and scanning electron microscopy, Western
      blot analysis, and analysis of glucose use and lactate production. The neuronal
      retinal precursor cell line cultured in a bioreactor gave rise to most retinal
      cell types seen in monolayer culture. They formed composite structures with cell
      covered beads associated with one another in a tissue-like array. The beginning
      of layering and/or separation of cell types was observed. The neuronal cell types
      previously seen in monolayer cultures were also seen in the bioreactor. Some of
      the retinal cells differentiate into photoreceptors in the bioreactor with well
      developed outer segment-like structures, a process that is critical for retinal
      function. Moreover, the neuronal cells that were generated resembled their in
      vivo phenotype more closely than those grown under other conditions. Outer
      segments were almost never seen in the monolayer cultures, even in the presence
      of photoreceptor-inducing growth factors such as basic fibroblast growth factor
      (bFGF) and transforming growth factor (TGF-alpha). Muller cells were occasionally
      seen when retinal, RPE cells were cocultured with retinal cells in the
      bioreactor. These have never been seen in this retinal cell line before. Cells
      grown in the bioreactor expressed several proteins specific for the retinal cell
      types: opsin, protein kinase C-alpha, dopamine receptor D4, tyrosine hydroxylase,
      and calbindin.

PMID- 14653620
TI  - Transplantation of embryonic porcine neocortical tissue into newborn rats.
AB  - Several previous studies, suggesting the potential use of embryonic xenografts in
      the treatment of neurological disorders, indicate that neural growth and axonal
      guidance factors may function across species. In this light, blocks of fetal
      porcine neocortex were grafted into small cortical lesion cavities made in
      newborn rats. Sacrifice at 3-12.5 weeks posttransplantation revealed healthy
      looking grafts in several animals. Apparent graft rejection evidenced by areas of
      necrosis and OX1 reactivity was observed in some of the older transplants.
      Treatment of nursing mothers or of postweaning newborns with cyclosporin A did
      not appear to promote graft survival. Some transplants grew to extremely large
      proportions and were characterized by bands of cells and bundles of axons as
      observed using immunohistochemical staining for pig neurofilament. Neurofilament
      positive axons projected from several of the grafts to course through the corpus
      callosum to the contralateral cortex or to course ipsilaterally within the
      subcortical white matter, where labeled fibers could be traced to the midbrain
      crus cerebri in older transplants. Bundles of axons were also observed coursing
      within the ipsilateral caudate putamen where terminal branching was apparent. The
      normal course of transplant efferents within the host brain indicates that
      growing pig axons can respond to rodent axonal guidance factors.

PMID- 14653621
TI  - Improved efficacy of stem cell labeling for magnetic resonance imaging studies by
      the use of cationic liposomes.
AB  - Labeling stem cells with FDA-approved superparamagnetic iron oxide particles
      makes it possible to track cells in vivo with magnetic resonance imaging (MRI),
      but high intracellular levels of iron can cause free radical formation and
      cytotoxicity. We hypothesized that the use of cationic liposomes would increase
      labeling efficiency without toxic effects. Rabbit skeletal myoblasts were labeled
      with iron oxide by: 1) uptake of iron oxide incorporated into cationic
      transfection liposomes (group I) or 2) customary endocytosis (group II). In both
      groups, cell proliferation and differentiation were measured and toxicity was
      assayed using trypan blue and ratio fluorescence microscopy with BODIPY 581/591
      C11. The effects of the intracellular iron oxide on magnetic resonance image
      intensities were assessed in vitro and in vivo. Both methods resulted in uptake
      of iron intracellularly, yielding contrast-inducing properties on MRI images. In
      group II, however, incubation with iron oxide at high concentrations required for
      endocytosis caused generation of free radicals, a decrease in proliferation, and
      cell death. Cytotoxic effects in the remaining cells were still visible 24 h
      after incubation. Conversely, in group I, sufficient intracellular uptake for
      detection in vivo by MRI could be achieved at 100-fold lower concentrations of
      iron oxide, which resulted in a high percentage of labeled cells, high retention
      of the label, and no cytotoxic effects even after stressing the cells with a
      hypoxia-reoxygenation insult. The use of cationic liposomes for iron oxide stem
      cell labeling increases labeling efficiency approximately 100-fold without toxic
      effects. This technique results in high-contrast-inducing properties on MRI
      images both in vitro and in vivo and could thus be a valuable tool for tracking
      stem cells noninvasively.

PMID- 14653622
TI  - Long-term cell survival and hemodynamic improvements after neonatal cardiomyocyte
      and satellite cell transplantation into healed myocardial cryoinfarcted lesions
      in rats.
AB  - Cell engraftment is a new strategy for the repair of ischemic myocardial lesions.
      The hemodynamic effectiveness of this strategy, however, is not completely
      elucidated yet. In a rat model of cryothermia-induced myocardial dysfunction, we
      investigated whether syngeneic transplantation of neonatal cardiomyocytes or
      satellite cells is able to improve left ventricular performance. Myocardial
      infarction was induced in female Lewis rats by a standardized cryolesion to the
      obtuse margin of the left ventricle. After 4 weeks, 5 x 10(6) genetically male
      neonatal cardiomyocytes (n = 16) or satellite cells (n = 16) were engrafted into
      the myocardial scar. Sham-transplanted animals (n = 15) received injections with
      cell-free medium. Sham-operated animals (n = 15) served as controls. Left
      ventricular performance was analyzed 4 months after cell engraftment. Chimerism
      after this sex-mismatched transplantation was evaluated by detection of PCR
      amplified DNA of the Y chromosome. The average heart weight of the infarcted
      animals significantly exceeded that of controls (p < 0.05). In sham-transplanted
      animals, mean aortic pressure, left ventricular systolic pressure, aortic flow
      (indicator of cardiac output), and left ventricular systolic reserve were
      significantly lower (p < 0.05) compared with sham-operated controls. This was
      associated with deterioration of ventricular diastolic function (maximal negative
      dP/dt, time constants of isovolumic relaxation; p < 0.05). Transplantation of
      satellite cells was found more effective than transplantation of neonatal
      cardiomyocytes, resulting in i) normalization of mean aortic pressure compared
      with sham-operated controls, and ii) significantly improved left ventricular
      systolic pressure and aortic flow (p < 0.05) compared with sham-transplanted
      animals. Left ventricular systolic reserve and diastolic function, however, were
      improved by neither satellite cell nor neonatal cardiomyocyte transplantation.
      Analysis of male genomic DNA revealed 3.98 +/- 2.70 ng in hearts after neonatal
      cardiomyocyte engraftment and 6.16 +/- 4.05 ng in hearts after satellite cell
      engraftment, representing approximately 10(3) viable engrafted cells per heart.
      Our study demonstrates i) long-term survival of both neonatal cardiomyocytes and
      satellite cells after transplantation into cryoinfarcted rat hearts, ii) slight
      superiority of satellite cells over neonatal cardiomyocytes in improving global
      left ventricular pump performance, and iii) no effect of both transplant
      procedures on diastolic dysfunction.

PMID- 14653624
TI  - The effects of poly(ethyleneimine) (PEI) molecular weight on reinforcement of
      alginate hydrogels.
AB  - Alginate hydrogels are widely used for cell encapsulation and transplantation,
      and they are frequently surface reinforced with secondary polymers to enhance
      their mechanical rigidity and stability. We hypothesized that the molecular
      weight (MW) of the polymer utilized to reinforce alginate would be an important
      factor in their stability, particularly when the gel network was homogeneously
      reinforced with the polymer. This hypothesis was investigated with alginate
      hydrogels cross-linked with Ca2+, and reinforced throughout the bulk of the gel
      with poly(ethyleneimine) (PEI) having different MWs. Interactions between the two
      polymers became significant following gelation, leading to higher elastic moduli
      (E) than gels with no PEI. The decrease in E of gels incubated in isotonic salt
      solutions over time, utilized as an indication of gel break down, was ameliorated
      with an increase in the MW of the PEI. In addition, the dependencies of the
      moduli and viscoelasticity on the temperature also became smaller with the use of
      high MW PEI. This is likely due to the limited mobility of high MW PEI, leading
      to a higher energy for dissociation. The stable interactions between the alginate
      and PEI prevented alterations of the pore structure in the gels, and slowed the
      deterioration of gel properties even under continuous agitation in a bioreactor.
      The results of this study will likely be useful in designing alginate
      encapsulation strategies for various applications.

PMID- 14653623
TI  - Polymers for induction of revascularization in the rat fascial flap: application
      of vascular endothelial growth factor and pancreatic islet cells.
AB  - One of the major obstacles in transplanting avascular tissue or metabolically
      active cells for ischemic diseases is the loss of transplanted cells due to lack
      of oxygen and nutrients in the early posttransplantation period. Biodegradable
      polymeric tissue engineering scaffolds and hydrogels have a potential to
      incorporate cells or cellular organoids such as islets of Langerhans and growth
      factors. In this study, we tested the efficiency of two types of polymeric
      materials to carry recombinant human vascular endothelial growth factor (rhVEGF)
      or pancreatic tumor cell lines, namely Ins-1 and AR42J, for the induction of new
      vessels. Chitosan hydrogel fibers with micropores were prepared and molded into a
      cylinder construct (5 mm phi; 8 mm height). Macroporous PLGA scaffolds with a
      pore size of 250-400 microm were prepared and cut into cylinders (6 mm phi; 3 mm
      height). Both chitosan and PLGA constructs were loaded with rhVEGF (3 microg) or
      seeded with the cell lines (5 x 10(5) cells and 3 x 10(5) cells/construct,
      respectively, for AR42J and INS-1 cells), and transplanted into the fascial flaps
      of Wistar rats. At distinct time points up to 4 weeks postimplantation, polymers
      were explanted, fixed, and vessel density was counted on sections stained with
      anti-Factor-VIII antibody. Additionally, the kinetics of rhVEGF release from PLGA
      microspheres (phi of 50-80 microm) was determined using VEGF Elisa. Endogenous
      VEGF release from pancreatic rat cell lines was also determined. Light microscopy
      study was performed on H&E-stained paraffin sections of the islet-polymer
      samples. The vascular density of rhVEGF-loaded chitosan constructs was increased
      fourfold 2 weeks after subcutaneous transplantation compared with rhVEGF-unloaded
      controls (465 +/- 144 vs. 104 +/- 80 vessels per mm2, p < 0.05). Protein leakage
      occurred, but was not observed after 2 weeks. Higher insulin content was detected
      in rat islet grafts transplanted following VEGF application. More than 50% of
      total rhVEGF was released on the first day of in vitro culture of PLGA
      microspheres. rhVEGF secretion had another, but smaller, peak on the third day
      followed by a constant release. By comparison, endogeneous VEGF secretion of
      pancreatic tumor cells was measured within a 3-day culture period. Biodegradable
      polymer scaffolds and hydrogels may have potential use as solid supports to
      induce angiogenesis for pancreatic cell transplantation.

PMID- 14653625
TI  - Autologous transplantation of gingival fibroblast-like cells and a
      hydroxylapatite complex graft in the treatment of periodontal osseous defects:
      cell cultivation and long-term report of cases.
AB  - Autogenous cell transplantation via hydroxylapatite (HA) vehicle has been
      reported to have beneficial effects on the treatment of human periodontal osseous
      defects. The aim of this study was to explore the possibility of using gingival
      fibroblast-like cells in the therapy of osseous defects caused by inflammatory
      periodontitis by reporting long-term results of gingival fibroblast-coated
      hydroxylapatite (GF-HA) grafting for healing these defects. Gingival fibroblasts
      were cultured from healthy gingivae of treated subjects. Growth of cells on HA
      particles was established in vitro, and then the GF-HA complex was transplanted
      into the periodontal osseous defects. Clinical parameters of gingival and plaque
      indices, probing depth, and periapical x-ray were monitored at baseline and at
      various periods from 50 months to 6 years after surgery. Grafting with only HA in
      the osseous defects of the same patient was used for comparison. The present
      study shows that GF-HA-treated sites could achieve marked pocket reduction and
      probing attachment gain at reentry and later recalls. Good clinical bone filling
      of osseous defects in GF-HA-treated sites was also demonstrated in periapical
      radiographs (increased bone height and reappearance of the crestal cortex) and in
      some reentry sites. One HA-treated site was filled with connective tissue only,
      and the absence of new bone formation was noted during a reentry operation.
      Another HA-treated site exhibited a comparable increase in radiographic density,
      while part of HA particles were gradually lost in longer recalls. These limited
      observations conclude that GF-HA grafting may provide a treatment modality
      leading to regeneration of periodontal tissues in periodontitis-affected osseous
      defects. Further studies including more cases and demonstration of the deposition
      of differentiated periodontal tissues are necessary before further application of
      this therapy.

PMID- 14653626
TI  - Modulation of specific beta cell gene (re)expression during in vitro expansion of
      human pancreatic islet cells.
AB  - The need for transplantable beta cells with a stable phenotype has given rise to
      several strategies including the expansion of existing pancreatic islets and/or
      growth of new ones. In vitro studies of beta cell proliferation on extracellular
      matrices plus growth factors have highlighted a possible cell expansion
      technique; however, the technique was accompanied with loss of insulin secretion.
      Herein we showed that human islet cell proliferation was marked by a decreased
      expression of specific differentiation markers, particularly insulin, insulin
      promoting factor-1 (IPF-1), and glucokinase. After a 6-day expansion period, we
      tried to reexpress the beta cell differentiation markers with compounds known for
      their differentiation and/or insulin-secreting properties. Sodium butyrate was a
      potent factor of IPF-1, insulin, and glucokinase gene reexpression; it also
      clearly induced secretion of gastrin, a known neogenic factor. Other compounds,
      namely TGF-beta, calcitriol, GLP-1, and activin A, efficiently enhanced the
      glucose sensor machinery, particularly Glut-1 and glucokinase, thus triggering
      glucose responsiveness. Our results indicate that specific beta cell gene
      expression may be induced after expansion and dedifferentiation. This rekindles
      interest in human beta cell expansion. The possible stabilization of specialized
      genes needed by beta cells to fulfill their role as nutrient sensors and
      metabolic regulators may also be of interest to ensure graft maintenance and
      efficiency.

PMID- 14653627
TI  - The bag method for islet cell infusion.
AB  - As islet cell transplantation gains increasing interest following results
      published by the Edmonton group, results that have been successfully reproduced
      by several centers nationwide and abroad, the need of guidelines to standardize
      the procedure becomes highly important. We detail the key steps of the infusion
      procedure utilizing a closed gravity fed bag system utilized at our institution
      since 1990, which consists of a 600-ml transfer bag and a 150-ml rinse bag
      connected via sterile tubing. The use of gravity allows for a control rate of
      infusion as well as providing a safety mechanism through natural reduction of
      flow that parallels any increase in portal pressure, therefore allowing the
      operator to prevent precipitous pressure rises. Reports on significant rise in
      portal pressures during islet cell infusion as well as portal vein thrombosis
      have been published. Infusion at these centers was carried out using a syringe
      method. Using our technique, portal vein thrombosis (partial or complete) was not
      detected in any of the infusions performed at our institution. This method may be
      of assistance to minimize some of the observed complications associated with
      islet transplant procedures and has now been adapted by most centers performing
      clinical islet transplantation.

PMID- 14653628
TI  - Downstream morphological change in response to dam construction: a GIS based
      approach for the Lower Ord River, Western Australia.
AB  - Flow regulation in the Lower Ord River began in 1963 with the completion of the
      Kununurra Diversion Dam, part of a large-scale irrigation scheme in the far north
      of Western Australia. What was previously an ephemeral river punctuated by large
      flood events now contains permanent, regulated flows all year round, and
      fundamental changes in the downstream channel morphology are now evident. Further
      changes to the regulated flow regime are planned as part of the eventual
      expansion of the irrigation area. It is necessary to understand and document the
      channel responses that have occurred in the Lower Ord so far as a result of flow
      regulation. This paper presents a GIS based investigation into morphological
      change in the Lower Ord River. Geomorphic surface data are largely generated from
      sequential aerial photographs, calibrated using field observations and historical
      records. Results illustrate the changes in the total area of each surface type,
      the direction of change in bar evolution and the significance of changes in
      channel width throughout the study reach.

PMID- 14653629
TI  - Institutionalizing the option of dam removal: the New Hampshire initiative.
AB  - For two years, the State of New Hampshire has worked to institutionalize the
      option of dam removal. The high gradient streams that flow through the granite
      hills and mountains of this small northeastern state provided ideal conditions
      for dam construction, particularly during America's Industrial Revolution of the
      1800s when mills were constructed throughout the area. With more than 4,800 dams
      in the state's database, there are many opportunities for the removal of dams
      that no longer serve a useful purpose, have become a public safety hazard and
      impact the river environment. Efforts to facilitate removal of dams in New
      Hampshire include the formation of a River Restoration Task Force and the
      creation of a dam removal program within the state agency responsible for
      regulating dams. This has led to the removal of two dams in the past year, with
      approximately ten additional projects in various stages of planning. A history of
      this agency-led initiative, as well as a discussion of the program's strengths,
      challenges and goals for the future are presented.

PMID- 14653630
TI  - Groyne fields--sink and source functions of "flow-reduced zones" for water
      content in the River Elbe (Germany).
AB  - The role of man-made "flow-reduced zones" as a sink or a source of water content
      is unknown for the River Elbe, Germany. We measured and compared: a) the
      concentration of suspended matter at the inflow and the outflow of one special
      groyne field ("UFZ groyne field") weekly for a period of two years; and b) the
      intensity of oxygen metabolism within several groyne fields and the main stream
      during a Lagrangian survey. Under discharge conditions near or below mean water,
      we found a significant reduction of suspended particulate matter and particle
      bound nutrients in the "UFZ groyne field". In contrast, concentrations of most
      soluble water contents and chlorophyll a did not significantly change between in-
      and outflow. During the Lagrangian survey, pelagic production and respiration
      rates developed nearly identically in both the main stream and the adjacent
      groyne fields but oxygen time curves showed higher amplitudes for the groyne
      fields compared to the river. This higher net-oxygen production in the groyne
      fields is due to reduced water depth and reduced stream velocity. It enhances the
      concentration of oxygen in the main stream. The contrary results show the
      coexistence of both sink and source functions of "flow-reduced zones" in rivers.

PMID- 14653631
TI  - The potential contribution of the Queensland wet tropics region natural resource
      plan to river improvement and water quality.
AB  - This paper reports on work in progress on the new Wet Tropics Regional Natural
      Resource Management Plan and its potential to deliver river management and water
      quality outcomes. The plan is being prepared in accordance with the guidelines of
      the Nation Action Plan for Salinity and Water Quality/Natural Heritage Trust
      (NAP/NHT2). In particular the paper discusses the technical basis for priorities,
      target setting and implementation and the most effective instruments for
      achieving river improvement and water quality outcomes in the region.

PMID- 14653632
TI  - Water quality in sugar catchments of Queensland.
AB  - Water quality condition and trend are important indicators of the impact of land
      use on the environment, as degraded water quality causes unwelcome changes to
      ecosystem composition and health. These concerns extend to the sea, where
      discharges of nutrients, sediments and toxicants above natural levels are
      unwelcome, particularly when they drain to the Great Barrier Reef World Heritage
      Area and other coastal waters of Queensland. Sugarcane is grown in 26 major river
      catchments in Queensland, most in environmentally sensitive areas. This puts
      pressure on the Queensland Sugar Industry to manage the land in ways that have
      minimum adverse off-site impacts. Sugar researchers including CRC Sugar have been
      associated with water quality studies in North Queensland. These include
      investigations and reviews to assess the role of groundwater as a pathway for
      nitrate loss from canelands in the Herbert Catchment, to find causes of oxygen
      depletion in water (including irrigation runoff) from Ingham to Mackay, to use
      residues of superseded pesticides as indicators of sediment loss to the sea, and
      to assemble information on water quality pressure and status in sugar catchments.
      Key findings, plus information on input pressures are described in this paper,
      and areas of concern and opportunities discussed.

PMID- 14653633
TI  - Land capability and topographic data as a surrogate for the mapping and
      classification of wetlands: a case example from the Daly basin, Northern
      Territory, Australia.
AB  - The Daly River (catchment 53,000 km2) has the largest flow of all rivers in the
      Northern Territory and, due to the vast underground aquifers supplying the river,
      reliable flows of water and areas of high potential soils, is the centre of a
      region where water resource and agricultural development is being given serious
      consideration. As part of a larger assessment of environmental flow requirements,
      an inventory and risk assessment of water dependent ecosystems (wetlands) was
      undertaken for the Daly basin, a limestone dominated region, 19,382 km2 in size,
      located in the centre of the catchment. The assessment utilized geographic
      information system technology to collate, interrogate and analyse soil and
      topographic data that had been collected previously for the purpose of land
      capability analysis. The aggregated data were used as a surrogate for mapping the
      distribution of wetlands in the Daly basin. The land units mapped were composed
      of individual areas within which the soil, vegetation and landform exhibited a
      uniform pattern on aerial photographs. The wetland features mapped were
      classified using landform and hydroperiod as a basis and, to assist in the
      classification process, a ground-truthing exercise and a basin-wide low-level
      aerial survey were conducted.

PMID- 14653634
TI  - Modelling chloride-discharge relationships in Krishna river basin.
AB  - Chloride discharge relationships at several monitoring stations on the River
      Krishna in South India are investigated, both qualitatively and quantitatively,
      to identify probable source contributions. The chloride behaviour along the
      waterway is studied in detail to assess the source contributions at various
      monitoring stations falling within the study area. Seasonal variations in the
      intensity of rainfall cause wide variations in the quality of the River Krishna.
      As there is strong seasonal dependence between the flow in the river and
      chlorides, seasonal models are developed for prediction of concentrations and
      loads. Linear regression analysis is carried out to determine the model
      parameters. The predicted concentrations and loads are in agreement with the
      observed values within the uncertainty of data. As the area is characterized by
      distinct dry and wet seasons (based on rainfall distribution over the year), mass
      balances are used to differentiate between point and non-point source
      contributions to the river. In large river basins, monitoring all individual
      sources is difficult and/or impossible and expensive; hence the presented
      approach based on receiving water quality and flow serves as an alternative for
      modeling chlorides in the river basin. Results of the study can be used to
      emphasise water pollution control strategies.

PMID- 14653635
TI  - Environmental flow requirements in arid zone rivers--a case study from the Lake
      Eyre Basin, central Australia.
AB  - The ARIDFLO project takes a multi-disciplinary approach to the collection and
      analysis of data required to formulate appropriate environmental flow
      requirements for rivers in the Lake Eyre Basin. The key drivers of the ecological
      processes underpinning the health of these rivers are identified by modelling
      whole-of-ecosystem biological responses to hydrological events over a range of
      spatial and temporal scales. First, the hydrology of these poorly gauged (often
      ungauged) rivers needs to be modelled and validated to mimic real flow and
      inundation patterns at the catchment, reach and waterbody scale. Modelled and
      actual discharge data are then used to provide a suite of hydrological predictor
      variables which, in conjunction with other environmental variables, are used to
      model observed biotic responses. The key hydrologic and environmental drivers
      identified by the statistical models need to be taken into account when
      determining environmental flow requirements for these river systems. Further work
      is required to assess the predictive power of the models in the highly variable,
      complex systems of the Lake Eyre Basin rivers.

PMID- 14653636
TI  - Restoring biodiversity in the Gwydir Wetlands through environmental flows.
AB  - As part of the Water Reforms process, environmental flow rules have been
      progressively implemented in New South Wales rivers. The Integrated Monitoring of
      Environmental Flows (IMEF) is a major project established to better understand
      how rivers and associated wetlands respond to environmental water allocations.
      The results presented here represent the vegetation data collected for the
      testing of the hypothesis that "protecting or restoring a portion of freshes and
      high flows and otherwise maintaining natural flow variability will replenish
      anabranches and riverine wetlands, restoring their biodiversity". The study site
      is the Ramsar listed Gwydir Wetlands, located on the Gingham and Gwydir (Big
      Leather) Watercourses in the Lower Gwydir Valley, 100 km west of Moree. The
      expansion of irrigated agriculture in the lower Gwydir valley has severely
      altered flow regimes in the wetlands. The spread of the weed Phyla canescens
      (Lippia) is of major concern to landholders in the Gwydir Wetlands. Results
      indicate that Paspalum distichum (Water couch) and Eleocharis plana (Ribbed spike
      rush) can maintain dominance over Phyla canescens if flooding occurs on a semi
      regular basis. Conversely, Eichhornia crassipes (Water hyacinth) is a rampant
      noxious weed of open water in the Gwydir Wetlands, and has quickly spread in
      areas that are inundated for long periods. Management of this weed requires
      periodic drying of the wetlands to cause desiccation and death of the plants. The
      flooding requirement of individual species and plant associations in the Gwydir
      Wetlands are currently not fully understood. By providing better information on
      the consequence of different flows, the IMEF project will help to develop better
      management strategies to shift the dominance from introduced species such as P.
      canescens and E. crassipes to more desirable native plant species.

PMID- 14653637
TI  - Issues in environmental water allocation--an Australian perspective.
AB  - Environmental water allocation is a critical issue in Australia and
      internationally. It has been prominent in Australia for a little over ten years
      during which time major policy and scientific advances have been made, but little
      implementation. This paper examines current understanding of environmental water
      allocation across a broad range of disciplines including the biophysical
      sciences, social sciences, economics, law, and policy. Development of practical
      methods for assessing environmental water requirements and experience with
      implementation in Australia are discussed. The paper concludes with thoughts on
      future needs.

PMID- 14653638
TI  - Hydrotechnical facilities within the Chernobyl nuclear power plant exclusion
      zone: impacts on hydrologic regime and plant growth patterns of floodplain water
      bodies of the Pripyat River.
AB  - As result of the Chernobyl nuclear power plant accident the territory of the left
      bank flood-lands of the Pripyat River have undergone intensive radionuclide
      contamination. With the purpose of preventing the washing away of radioactive
      substances, a complex of flood protection dams was constructed. This construction
      changed the hydrological regime of these territories and caused overgrowth by
      higher aquatic plants. Absence of a flowing mode of reservoirs, the stagnant
      phenomena during spring and seasonal high waters on the embank site have caused
      amplification of eutrophication processes, swamping and, connected with it,
      increase of water-marsh floristic complex in the structure of the vegetative
      cover.

PMID- 14653640
TI  - Derivation of a salinity target for the Lower Murray Darling Valley.
AB  - The NSW Government commissioned catchment management boards (CMBs) to set the
      direction and process for catchment scale natural resource management. In the
      Lower Murray Darling, Rivers are highly regulated and water resources shared
      between three states. The Catchment Board only has jurisdiction over the northern
      bank of the Murray but salt and water enter the river from many locations
      upstream and along the area boundary. River salt and flow modelling has
      continually been improved to reflect and contribute to an increased understanding
      of salinity processes. The MDBC Salt Load study correlates 10 years of actual
      measured data with its modelled outputs, and estimates river salinities for 2020,
      2050 and 2100. Routing models such as SALTFLO and MURKEY generate percentile
      salinity levels at different nodes in the River Murray downstream of the Lower
      Darling confluence. National, Murray-Darling Basin and NSW salinity management
      policy and legislative requirements were considered, MDBC model output was used
      to ensure the interim targets are achievable, auditable, and appropriate to the
      catchment. The method for an end-of-valley river based target for salinity is
      described. A target of less than 463 microS/cm for Lock 6, a point in the lower
      reaches of the Murray River is recommended for year 2010. Catchment management
      targets that express the main river salinity risk in five hydrologically distinct
      management zones are also recommended. Salinity management changes are needed in
      each zone to meet the end-of-valley target.

PMID- 14653639
TI  - Pollutant sources investigation and remedial strategies development for the
      Kaoping River Basin, Taiwan.
AB  - The Kaoping River Basin, located in southern Taiwan, flows through approximately
      171 km and drains towards the South Taiwan Strait. It is the largest and the most
      intensively used river basin in Taiwan. Based on the results from the pollutant
      sources investigation and water quality analysis, the main water pollution
      sources of the Kaoping River were livestock wastewater from hog farms, municipal
      wastewater, industrial wastewater, leachate from riverbank landfills, and non
      point source (NPS) pollutants from agricultural areas in the upper catchment.
      Concern about the deteriorating condition of the river led the Government of
      Taiwan to amend the relevant legislation and strengthen the enforcement of the
      discharge regulations to effectively manage the river and control the pollution.
      The following remedial strategies have been taken to improve the river water
      quality since 2001: (1) hog ban in the upper catchment of the Kaoping River
      Basin, thus, 510 thousand hogs have been removed/relocated; (2) removal of
      riverbank landfills; (3) enforcement of the industrial wastewater discharge
      standards; (4) sewer system construction in five cities along the river corridor;
      (5) application of best management practices for NPS pollutant control; (6)
      application of natural wastewater treatment systems (e.g. land treatment,
      constructed wetland, overland flow, riverbank sedimentation/aeration pond) for
      domestic wastewater treatment in rural areas; and (7) construction of the
      watershed geographical information system (GIS) and real time water quality
      monitoring system to effectively monitor and manage the watershed. Recent water
      quality investigation results indicate that the biochemical oxygen demand (BOD)
      and nutrient loadings to the Kaoping River have been significantly reduced and
      the water quality has been improved after the implementation of the remedial
      strategies described above. Results and experience obtained from this study will
      be helpful in designing the watershed management strategies for other similar
      river basins.

PMID- 14653641
TI  - Response of Eucalyptus largiflorens to floodplain salinisation.
AB  - An analysis of the stable isotopes from the tree rings of Eucalyptus largiflorens
      on the Chowilla Floodplain was undertaken. This chronology of tree water use
      responses was compared to the known hydrological changes that have occurred due
      to the effects of river regulation. The isotope chronology indicates that E.
      largiflorens has always oscillated between groundwater and rain-derived soil
      water and river regulation has apparently had little effect on tree water sources
      over time. This result is surprising, but no doubt reflects the complexity of
      floodplain processes and interactions between trees, water and the landscape.

PMID- 14653642
TI  - The river Ganga of northern India: an appraisal of its geomorphic and ecological
      changes.
AB  - The Ganga is the most important perennial river originating from Gangotri in the
      snow-bound Himalayas about 3,900 m above mean sea level. Gorging a distance of
      about 220 km in the Himalayas, it enters the plain at Hardwar and after
      meandering and braiding over a distance of about 2,525 km through the Indo
      Gangetic plains, ultimately joins the Bay of Bengal. The course of this river has
      been changed due to: (i) subsurface geotectonic movement leading to change in
      slope of the deltaic plain and subsidence of the Bengal basin; (ii) changing
      pattern of water discharge with time; (iii) variations in sediment load. The
      environment of Ganga basin is also deteriorating with time due to severe natural
      episodes of periodic floods and storms as well as anthropogenic factors such as
      population growth, deforestation, agricultural activities, urbanisation,
      fertiliser and fossil fuel consumption and construction activities such as dams
      and bridges. All these have inconceivable adverse impacts on the health and
      natural regeneration capacity of the river basin. The presence of micropollutants
      in water and sediments of this river turns the system into being unsustainable to
      the biota. The present study synthesises the available information on the changes
      of its geological, geomorphological and ecological aspects and suggests some
      remedial measures to be adopted now and in future.

PMID- 14653643
TI  - Restoring the Mauri of Oruarangi Creek.
AB  - In recognition of the societal and cultural values of ecological restoration
      several community-based programs have been developed throughout the world. In
      particular those with interests in the field of freshwater and riparian
      management have developed numerous programs to encourage community involvement in
      their management. While each of these programs gives de facto recognition to an
      ethos typically espoused by indigenous peoples, the concerns, values and
      localised knowledge of indigenous peoples continues to remain excluded from the
      management process. In documenting key aspects of the proposed restoration of
      Oruarangi Creek this paper aims to provide an example of how the concerns, values
      and knowledge of local indigenous communities can form a major component of the
      restoration process.

PMID- 14653644
TI  - The development of an historical baseline of water balance and environmental
      flows.
AB  - This paper has been motivated by a desire to put some numbers beside the label of
      sustainability as is currently applied to water related issues. Of particular
      interest is a general estimate of the water balance and environmental flows
      during the time intervals before Aboriginal arrival, when the land was being
      managed in an environmentally sustainable manner by the Aboriginals, and most
      recently following European settlement. This will be considered in an Australia
      wide context, because the continent is geographically diverse, being mostly arid
      desert, with limited areas of fertile soils. Climate variation ranging from a hot
      tropical north to a cool temperate south will also be discussed. Attention will
      be given to the major factors that have influenced the water balance, including
      the extinction of Australian megafauna, the effects of "fire-stick" farming and
      the clearance of land for European agriculture with its consequences. It is hoped
      that the findings will increase our understanding of Australian water resources,
      and promote a greater appreciation of the fragility of this ancient landscape on
      which we dwell.

PMID- 14653645
TI  - Measuring the total value of a river cleanup.
AB  - The paper estimates the total value for the community of the cleanup of the
      Buriganga River. Dhaka, the capital of Bangladesh, was developed on the bank of
      the Buriganga River in the early 1600s. The river is now near dead mainly due to
      human interventions. The paper develops a hypothetical cleanup programme to
      improve the water quality, which will help the overall environment in and around
      the river. The value of this programme is estimated within the framework of total
      economic value; non-marketed benefits are measured through a contingent valuation
      survey and marketed benefits are estimated using market and shadow prices. The
      findings of the survey suggest that not only are a significant proportion of the
      residents willing to pay for the cleanup programme, but many are also willing to
      contribute in non-monetary ways (mainly their time). When the latter contribution
      is monetised, it represents 60% of the total value for the non-marketed benefits.
      The marketed benefits are estimated to represent 58% of the overall value of the
      cleanup programme (18.6 million US dollars/year). A failure to account for all
      benefits could lead to a gross underestimation of the desirability of providing
      public funding for the cleanup of dying rivers.

PMID- 14653646
TI  - Modelling the economic impact of environmental flows for regulated rivers in New
      South Wales, Australia.
AB  - The management of water resources across Australia is undergoing fundamental
      reform in line with the priorities identified by the Council of Australian
      Governments (COAG) in 1994. This includes reforms to the specification of
      property rights, the way the resource is shared between the environment,
      irrigators and other users, charges for water use and the operational management
      of the river systems. In New South Wales (NSW), a series of water sharing plans
      (WSPs) is being developed for each water source in the State including regulated
      rivers, unregulated rivers and groundwater aquifers. These plans, which are the
      mechanisms by which COAG reforms are being implemented, are being developed by
      community-based water management committees (WMCs). The role of the WMCs is to
      develop a plan that achieves a balance between environmental, economic and social
      outcomes. NSW Agriculture has assisted a number of WMCs by quantifying the
      economic impact of proposed WSP options on the irrigation community. This paper
      outlines the approach taken by NSW Agriculture to quantifying economic impacts on
      irrigators in regulated catchments and provides results of case studies in the
      Lachlan River Catchment which is heavily developed for irrigation.

PMID- 14653647
TI  - Who owns Australia's water--elements of an effective regulatory model.
AB  - This paper identifies and describes a number of global trends in regulatory
      theory and legal scholarship. It points out the huge level of complexity demanded
      by globalisation and the unfortunate complication of this is that there is legal
      indeterminacy. The legal indeterminacy springs from the desire to amend and alter
      existing models. That has been the thrust of the Council of Australian
      Governments changes to adapt and add huge amounts of complexity to a flawed
      system. This paper argues that an effective water regulatory model requires a
      fundamental re-examination of the concept of water ownership and a capturing by
      the State of the right to allocate rainfall. This foundation is effective and the
      way forward to deal with the key issues in this transition phase. The second key
      element to an effective regulatory model is the concept of performance-based
      assessment. This requires information and schemes to be set up to work out ways
      to monitor and evaluate the performance of the utility on selected criteria. For
      Australia at present there is a dire lack of agreed criteria on these key issues
      and these have the potential to pull apart the whole process. The key issues are
      indigenous rights, governance issues, public participation, alteration of pre
      existing rights and incorporation of environmental requirements.

PMID- 14653648
TI  - An introduction of co-management approach into Babon River management in
      Semarang, Central Java, Indonesia.
AB  - The Babon River lies over three regions, i.e. Semarang District where the
      upstream is located while downstream it passes through Semarang Municipality and
      Demak District. This river has been used for many purposes by the neighbouring
      communities (e.g. water source, canal disposal, mining, etc). Thereafter many
      transboundary environmental problems have arisen here. The environmental
      management strategy (using a top-down approach) such as Program Kali Bersih
      (Clean River Program) on Babon River, which had been implemented by the Bapedalda
      of Semarang Municipality, is not successfully achieving the targets. In the past,
      most policies were formulated based on top-down orientation. Hence, the
      communities' participation was not paid enough attention. Co-management is a
      participative-management approach to empower the stakeholders (related parties)
      to achieve a certain goal. This study seeks answers to the research questions:
      (1) whether the co-management approach has good prospects for managing the Babon
      River; and (2) what kinds of strategy should be formulated to empower the
      stakeholders to manage the Babon River in the study area. The study employed a
      multistage sampling method to select the location of the study areas and key
      persons sample. Rowosari, Penggaron Kidul and Karangtoro were selected to
      represent the upstream, middle stream and downstream areas, respectively. The
      descriptive statistics method had been used to describe the significance of river
      resource attributes' characters. Institutional analysis approach, introduced by
      Pomeroy and Williams, was adopted with necessary modification in this study. The
      results showed that the level of participation of the community in the three
      segments of the Babon River is different. The prospects for the co-management
      approach to manage the river resource in the study area are fairly good and in
      the upstream area are better than in the other two segments. The level of
      participation is far from complete; nevertheless the response from society
      towards development is quite good. There are five significant attributes in Babon
      River, which affect the community participation in river management, namely: (1)
      intensity of resource commercialisation; formal education of the community; and
      dependency of the community toward the resources, resource products distribution
      and resource damage. These variables could influence the pattern of participation
      of the community in the study area. The other stakeholders such as industrial or
      plant owners, academics, and the related institutions have not been explored in
      detail in this study. The co-management model that has been developed in this
      study has the prospect of encouraging the community and other stakeholders'
      empowerment in economic activities, natural resource conservation, and
      environmental law enforcement, as part of achieving the ultimate goal of
      sustainable environmental management.

PMID- 14653649
TI  - Community-based river management in Southeast Sulawesi, Indonesia: a case study
      of the Bau-Bau River.
AB  - In this paper we explain the current condition of the Bau-Bau River, examine
      community participation for management of the river system, and consider options
      for improving the institutional capacity for a community-based approach. This
      assessment is based on a research project with the following objectives: (1)
      analyse the biophysical and socio-economic condition of the river as a basis for
      future planning; (2) identify current activities which contribute waste or
      pollution to the river; (3) assess the status and level of pollution in the
      river; (4) analyse community participation related to all stages of river
      management; and (5) identify future river management needs and opportunities. Due
      to the increasing population in Bau-Bau city, considerable new land is required
      for housing, roads, agriculture, social facilities, etc. Development in the city
      and elsewhere has increased run-off and erosion, as well as sedimentation in the
      river. In addition, household activities are generating more solid and domestic
      waste that causes organic pollution in the river. The research results show that
      the water quality in the upper river system is still good, whilst the quality of
      water in the vicinity of Bau-Bau city, from the mid-point of the watershed to the
      estuary, is not good, being contaminated with heavy metals (Cd and Pb) and
      organic pollutants. However, the levels of those pollutants are still below
      regulatory standards. The main reasons for pollution in the river are mainly lack
      of management for both liquid and solid wastes, as well as lack of community
      participation in river management. The government of Bau-Bau city and the
      community are developing a participatory approach for planning to restore and
      conserve the Bau-Bau River as well as the entire catchment. The activities of
      this project are: (1) forming institutional arrangements to support river
      conservation; (2) implementing extension initiatives to empower the community;
      (3) identifying a specific location to establish an urban forest; (4)
      implementing demonstration projects for liquid system management; (5) promoting
      coordination amongst the different organisations and agencies in the catchment;
      (6) improving domestic waste transportation; and (7) recycling waste to create
      compost material to become an income source for the community.

PMID- 14653650
TI  - Reality of irrigation water use and suggestions for better management: a
      comparison of two schemes from Sri Lanka.
AB  - In the dry zone of Sri Lanka, where agriculture is the main livelihood, both
      farmers and water managers target the best use of water. System H is an area that
      had been developed for irrigated agriculture using diversions from the River
      Mahaweli. Study of water use practices was carried out in two irrigation schemes
      where farmers cultivate the same crop in one-hectare allotments under the support
      and supervision of the same regional authority. Records of water use and
      agriculture are not well maintained. Using field visits, discussions with
      farmers, and meetings with officials were used to fill data gaps and three water
      issue scenarios were compared. Results of each scheme varied because water
      release and rotation practices for crop growth are quite different from each
      other, canal efficiency assumptions are different, land preparation, water use
      and quantity are dissimilar, and water releases do not consider much about growth
      stages. The study indicated that use of challenging water issues considering co
      ordinated and rational grouping of canals could lead to a saving of 10-30 cm of
      water per unit area. A discussion of the need for a critical evaluation of
      guidelines and the present practice of cultivation is included.

PMID- 14653651
TI  - Near surface water balance in the Northern Murray-Darling Basin.
AB  - The water balance allows the calculation of deep drainage from other components
      of the hydrological cycle. Deep drainage has been linked to outbreaks of dryland
      and irrigated salinity. Until recently, deep drainage was not considered to be an
      issue on the alluvial plains of the Northern Murray-Darling Basin. Recent
      simulation studies and calculations using the water balance suggest that
      substantial deep drainage occurs under irrigated agriculture. However, these
      estimates have large uncertainties due to possible errors in measurement,
      calculation and due to spatial variability. On a catchment scale the relative
      area under a certain land use as well as the connection to local groundwater and
      the influence of anomalies such as prior streams needs to be considered. This
      paper discusses the current state of knowledge on the water balance in the
      Northern Murray-Darling Basin and highlights the need for a concentrated effort
      to measure all the components of the water balance in this area, as well as the
      effect on shallow groundwater quality and levels.

PMID- 14653652
TI  - Groundwater-surface water interaction in inland New South Wales: a scoping study.
AB  - Groundwater and surface water have traditionally been managed separately in New
      South Wales (NSW). However, where rivers and aquifers are hydraulically
      connected, groundwater pumping has the potential to deplete streamflow. To
      highlight the major areas of connection in inland NSW, major streams were
      overlaid with groundwater depth data and the locations of irrigation bores. A
      consistent pattern was revealed related to basin geomorphology. The main areas of
      connection are the mid-sections of the major rivers where alluvial systems are
      well developed yet still narrow and constricted and groundwater depths are
      shallow. The mapping was validated and the processes explored by calculating
      water balances for a connected and disconnected reach in the Murrumbidgee River.
      These showed that, in highly connected reaches, river losses and/or gains are
      closely related to groundwater levels.

PMID- 14653653
TI  - The Aral Sea: problems, legends, solutions.
AB  - A lot of legends have been created around the Aral Sea. Some of them were born
      during the Soviet time but there are already new ones that have arrived recently.
      Those legends came to be the barriers to solving the problem. There are also
      barriers created by the status quo mentality of local authorities. But mutual
      understanding is the biggest problem among countries sharing water resources. It
      is suggested to create an Ecological Economics Unit of the Biosphere (EEUB)
      managed by an executive body not affiliated to any country. Despite the borders
      the EEUB should unite the economics of neighborhood countries to protect the
      nature.

PMID- 14653654
TI  - Linking atmospheric circulation to daily rainfall patterns across the
      Murrumbidgee River Basin.
AB  - The hydrological cycle in Australia covers an extraordinary range of climatic and
      hydrologic regimes. It is now widely accepted that Australian hydrology is
      significantly different from all other regions and continents with the partial
      exception of southern Africa. Rainfall variability is very high in almost all
      regions with respect to amount and the lengths of wet and dry spells. These
      factors are keys to the behaviour and health of Australian aquatic ecosystems and
      water resources. Thus assessment of how rainfall may change under a potential
      future climate is critical. For a case study of the Murrumbidgee River Basin
      (MRB), a statistical downscaling model that links broad scale atmospheric
      circulation to multi-site, daily precipitation is assessed using observed data.
      This model can be driven with climate model simulations to produce rainfall
      scenarios at the scale required by impacts models. These can then be used in
      probabilistic risk assessments of climate change impacts on river health. These
      issues will be discussed in the context of assessing the potential impacts of
      precipitation changes due to projected climate change on river health.

PMID- 14653655
TI  - Sobering thoughts.

PMID- 14653656
TI  - A look at the national health crisis of drunk driving.

PMID- 14653657
TI  - Detecting and preventing dementia... but what about delirium?

PMID- 14653658
TI  - Nystagmus testing in intoxicated individuals.
AB  - BACKGROUND: Law enforcement officers routinely conduct psychophysical tests to
      determine if an impaired driver may be intoxicated or in need of medical
      assistance. Testing includes assessment of eye movements, using the Horizontal
      Gaze Nystagmus (HGN) and Vertical Gaze Nystagmus (VGN) tests, which are conducted
      at roadside by patrol officers. These tests previously have been validated when
      the subject is placed in a standing posture with head upright. However, certain
      conditions require that the subject be tested while seated or supine. Under these
      conditions, Positional Alcohol Nystagmus (PAN) could be induced and mistaken for
      HGN or VGN. METHODS: The study was conducted at law enforcement training academy
      alcohol workshops in the Pacific Northwest. Ninety-six volunteer drinkers were
      tested when sober and three times after drinking alcohol by 40 volunteer officers
      experienced in administering the tests. Blood alcohol concentration (BAC) was
      measured objectively with a calibrated breath analysis instrument each time a
      subject was tested. RESULTS: The number of eye movement signs observed during the
      HGN test at any posture increases with increasing BAC. The presence of VGN at any
      test posture occurs only in the presence of signs of HGN and only at high levels
      of impairment. PAN was most often observed at BACs of 0.08% and higher, but was
      never confused with the observation of HGN or VGN, regardless of test posture.
      CONCLUSIONS: The HGN test administered in the standing, seated, and supine
      postures is able to discriminate impairment at criterion BACs of 0.08% and 0.10%.
      The VGN test can identify high levels of impairment at any test posture.
      Therefore, these tests can be used by an officer to determine if a driver is
      impaired, regardless of whether the driver is standing, seated, or supine.

PMID- 14653660
TI  - Coherent motion threshold measurements for M-cell deficit differ for above- and
      below-average readers.
AB  - BACKGROUND: Research during the past 20 years has influenced the management of
      diagnosis and treatment of children identified as having learning-related vision
      problems. The intent of this study is to determine whether coherent motion
      threshold testing can distinguish better-than-average non-disabled (ND) readers
      from those who are moderately reading disabled (RD) among sixth-grade students.
      METHOD: A sample of 23 better-than-average non-disabled readers (> or = 80th
      percentile) and 27 moderately disabled readers (< or = 32nd percentile) were
      identified using a standardized reading comprehension test. Each participant was
      tested for coherent motion threshold. Previous psychophysical and fMRI research
      with adults suggests that coherent motion threshold is a valid measure of
      magnocellular (M-cell) integrity. RESULTS: The average of two coherent motion
      threshold trials was significantly greater for moderately reading disabled
      subjects than for above-average readers (p < 0.01). The mean threshold percentage
      of dots required to observe lateral motion was 9.2% for moderately reading
      disabled readers and 4.6% for superior readers (p = 0.001). CONCLUSION: The
      outcome of this preliminary study provides an efficient procedure to identify
      sixth-grade students whose reading disability may be associated with an M-cell
      deficit. Our previous investigations involving visual processing, visual
      attention, and oculomotor therapy have resulted in significant improvements in
      reading comprehension, visual attention, and eye movements. It remains to be
      demonstrated whether vision therapy has an impact on the M-cell deficit, as
      measured with coherent motion threshold testing for moderately disabled readers.

PMID- 14653661
TI  - Diabetic retinopathy on a new scale.

PMID- 14653662
TI  - The practice prospecting process.

PMID- 14653663
TI  - When the patient is hearing-impaired.

PMID- 14653664
TI  - Twelve simple ways to help avoid claims rejections.

PMID- 14653659
TI  - Alternative arrangements for the delivery of eye care services within staff model
      managed care organizations.
AB  - BACKGROUND: Eye care services, though accounting for only a small fraction of
      healthcare costs, encompass a unique spectrum of professional staffing options
      that can enhance efficiency and decrease costs within staff model managed care
      organizations. METHODS: This study was designed to describe and assess
      alternative staffing arrangements and cost implications for the delivery of eye
      care services by optometrists, ophthalmologists, and primary care physicians
      within staff model managed care organizations. The clinical records of individual
      patients--rather than administrative and billing files--at three managed care
      organizations are the principal source of information. Clinical auditors
      extracted data on ambulatory eye care services provided for conjunctivitis,
      corneal abrasion/erosion, cataract, diabetic retinopathy, glaucoma, and macular
      degeneration. RESULTS: Our findings document the substantial role optometrists
      play in the delivery of eye care, whether they provide the care independently or
      in collaboration with an ophthalmologist. The levels of remuneration for
      optometrists are roughly one third to one half the annual rate for
      ophthalmologists. Staffing arrangements that use optometrists to the full extent
      of their professional training can provide significant cost savings. CONCLUSIONS:
      The cost-effectiveness of using the services of optometrists capable of
      delivering high-quality eye care can be demonstrated. Potential cost savings for
      staff model managed care organizations may accrue if the roles, functions, and
      availability of eye providers are adjusted.

PMID- 14653666
TI  - Dimethylthiocarbamate (DMTC): an alcohol protecting group.
AB  - Dimethylthiocarbamates (DMTCs), prepared from the corresponding alcohols using
      commercial dimethylthiocarbamoyl chloride, are spectrally simple, achiral, and
      nonpolar. DMTCs are moderately to highly stable to a wide range of reagents and
      conditions including metal hydrides, hydroboration, ylides, NaOH, HCl,
      organolithiums, Grignards, DDQ, PCC, Swern, n-Bu(4)NF, CrCl(2), heat, and Lewis
      acids. They are readily removed by NaIO(4) or H(2)O(2) in the presence of other
      common alcohol protecting groups. [structure: see text]

PMID- 14653667
TI  - Chiral alpha,beta-dialkoxy- and alpha-alkoxy-beta-aminostannanes: preparation and
      copper-mediated cross-coupling.
AB  - Addition of Zn(n-Bu(3)Sn)(2) to prochiral aldehydes affords anti-alpha,beta
      dialkoxy- and anti-alpha-alkoxy-beta-aminostannanes in good yield (up to 77%) and
      excellent diastereoselectivity (up to 98% de). syn-Isomers are accessed from the
      initial adducts via Mitsunobu inversion/saponification. The corresponding
      thionocarbamates undergo mild Cu(I)-mediated cross-coupling with a variety of
      organic halides, inter alia, allylic, cinnamylic, propargylic, and acetylenic,
      with retention of configuration. [reaction: see text]

PMID- 14653669
TI  - A dramatic effect of aryloxo ligands on the titanium-catalyzed hydroamination of
      alkynes.
AB  - The aryloxotitanium complex 1 is a highly chemo- and regioselective catalyst for
      intermolecular hydroamination of terminal alkynes. Branched imines are obtained
      in good to excellent yield (up to 99%) with various primary aromatic and
      aliphatic amines. [reaction: see text]

PMID- 14653668
TI  - Novel synthesis of 3-azabicyclo[3.1.0]hexanes by unusual palladium(0)-catalyzed
      cyclopropanation of allenenes.
AB  - Novel stereoselective synthesis of 3-azabicyclo[3.1.0]hexanes from allenenes is
      presented. Treatment of N-protected 4-alkyl-4-(N-allyl)amino allenes with allyl
      carbonate and a catalytic amount of Pd(2)(dba)(3).CHCl(3) in MeCN leads to
      stereoselective formation of the 3-azabicyclo[3.1.0]hexane framework in moderate
      to good yields. [reaction: see text]

PMID- 14653670
TI  - Stereoselective ring opening of meso bicyclic hydrazines: a straightforward
      approach to hydrazino cyclopentenic cores.
AB  - The diastereoselective synthesis of hydrazinocyclopentenes 6 or 7 can be achieved
      in a straightforward manner from Diels-Alder adduct 4 using an acid-catalyzed
      rearrangement or a palladium-catalyzed allylic substitution reaction. In the
      latter case, enantioenriched compounds with ee values up to 58% can be obtained
      when an appropriate chiral ligand is used. [reaction: see text]

PMID- 14653671
TI  - First efficient and general copper-catalyzed [2,3]-rearrangement of
      tetrahydropyridinium ylids.
AB  - The factors affecting the copper-catalyzed rearrangement of ammonium ylids
      derived from tetrahydropyridines and diazoesters have been examined,and the first
      examples of high-yielding metal-catalyzed [2,3]-sigmatropic rearrangements of a
      wide range of such ylids are reported. The nature of the alpha-substituent in the
      diazo component of the reaction has a dramatic effect upon the yields of the
      reaction, with electron-withdrawing substituents enhancing the yield of the
      reaction. [reaction: see text]

PMID- 14653672
TI  - Siloxane-based cross-coupling of bromopyridine derivatives: studies for the
      synthesis of streptonigrin and lavendamycin.
AB  - Highly functionalized 4-bromopyridines were prepared and found to undergo
      fluoride-promoted, Pd-catalyzed cross-coupling with aryltrialkoxysilanes to give
      sterically demanding biaryls. The 3-nitro-4-bromopyridine derivative coupled in
      good yield with TBAT (tetrabutylammonium triphenyldifluorosilicate) to provide a
      biaryl adduct that serves as a model system for the total synthesis of the
      antitumor antibiotics streptonigrin and lavendamycin. [reaction: see text]

PMID- 14653673
TI  - The first transformation of aliphatic alpha,beta-epoxyamides into alpha
      hydroxyamides.
AB  - A general synthesis of aliphatic alpha-hydroxyamides with total regioselectivity
      by a reductive cleaveage of the C(beta)-O bond of aliphatic alpha,beta
      epoxyamides, promoted by samarium diiodide and MeOH, is described. The treatment
      of enantiopure aliphatic alpha,beta-epoxyamides afforded enantiomerically
      enriched aliphatic alpha-hydroxyamides. A radical mechanism has been proposed to
      explain this reaction. [reaction: see text]

PMID- 14653674
TI  - Molecular tectonics. Dendritic construction of porous hydrogen-bonded networks.
AB  - Molecules that associate to form porous networks can be made by attaching
      multiple hydrogen-bonding sites to suitable cores. Pentaerythrityl tetraphenyl
      ether, a four-armed core, is the progenitor of dendritic derivatives with more
      arms, including dipentaerythrityl hexaphenyl ether 7. An advantage of such
      dendritic derivatives is that the resulting networks are held together by larger
      numbers of intermolecular hydrogen bonds. [structure: see text]

PMID- 14653675
TI  - Post-coordination of multinuclear transitional metal clusters to azulene-based
      polymers: a novel strategy for tuning properties in pi-conjugated polymers.
AB  - Direct treatment of azulene-thiophene copolymers with Ru(3)(CO)(12) led to unique
      examples of coordination of a multinuclear transition metal cluster to conjugated
      polymers. The polymer-metal cluster formation could be confirmed by (1)H NMR
      spectroscopic studies, and the coordination mode could be deduced from the
      crystallographic structure of model compounds. The composition of ruthenium
      carbonyl cluster could be used as a governing factor to tune the electronic,
      optical, and morphological properties of the organometallic polymers. [structure:
      see text]

PMID- 14653676
TI  - Intramolecular aromatic nucleophilic substitution of the benzimidazole-activated
      nitro group.
AB  - A wide range of 2-(2-nitrophenyl)-1H-benzimidazoles undergo high-yielding
      intramolecular S(N)Ar of nitrite with N-pendant alkoxides under mild conditions
      (DMF, rt). When this operationally simple process is carried out at elevated
      temperatures in the presence of excess NaH, the initially formed S(N)Ar products
      are converted to the corresponding N-vinyl-substituted 2-(2-hydroxyphenyl)-1H
      benzimidazoles via base-catalyzed isomerization. [reaction: see text]

PMID- 14653677
TI  - Comparative effects of conjugated and deconjugated isomeric enones on the
      transannular Diels-Alder reaction.
AB  - Two isomeric cyclic trienones 2 and 3 (with four methyl esters at positions 3 and
      10) underwent transannular Diels-Alder (TADA) reaction at very different
      temperatures. This drastic difference could be traced to the capacity of the
      enone dienophile to be conjugated or unconjugated at the transition state.
      Molecular modeling could confirm this explanation. The calculated enone proved to
      be very distorted in transition state ts2, and the TADA reaction temperature was
      accordingly much higher than the one corresponding to ts3 in which the enone was
      flat. [reaction: see text]

PMID- 14653678
TI  - Complete reversal in regioselectivity in the Baeyer-Villiger reaction of an alpha
      CF(3)-ketone and theoretical rationale for axial orientation of sterically
      demanding CF(3) group at the transition state.
AB  - The regioselectivity of the Baeyer-Villiger reaction of alpha-CF(3)-ketone is
      completely reversed from that in alpha-F(eq)-ketone. Theoretical study
      rationalized that the reaction proceeds with the sterically demanding CF(3) group
      in an axial orientation by strong dipole interaction. The guiding principle that
      strong dipole interaction can overcome steric repulsion as a determining factor
      not only in regio- but also in stereocontrol is proposed. [reaction: see text]

PMID- 14653679
TI  - Dipole interaction-controlled stereoselectivity in aldol reaction of alpha-CF3
      enolate with fluoral.
AB  - The stereoselectivity of a reaction is generally determined by minimizing steric
      repulsion. However, the aldol reaction of alpha-CF(3)-ketone (Z)-enolate with
      fluoral anomalously gave an anti-aldol through a sterically demanding transition
      state, because of the strong dipole interaction of the two CF(3) groups. We have
      thus disclosed a paradigm shift from steric to electronic control of reaction
      stereoselectivity. [reaction: see text]

PMID- 14653680
TI  - Switching between novel samarium(II)-mediated cyclizations by a simple change in
      alcohol cosolvent.
AB  - Gamma,delta-unsaturated ketones undergo two very different stereoselective
      cyclization reactions mediated by samarium(II) iodide depending upon the alcohol
      cosolvent used in the reaction. Switching between an unprecedented aldol
      spirocyclization and a novel cyclobutanol-forming process can be achieved simply
      by changing the alcohol cosolvent from methanol to tert-butyl alcohol. [reaction:
      see text]

PMID- 14653681
TI  - A practical and efficient synthesis of the C-16-C-28 spiroketal fragment (CD) of
      the spongistatins.
AB  - A practical and efficient route to the CD spiroketal (C-16-C-28) of the
      spongistatins is reported. Two stereocenters are introduced from chiral building
      blocks with the remainder introduced by substrate-controlled transformations. The
      key beta-keto-1,3-dithiane intermediate is generated by a dithiol conjugate
      addition to an ynone and the 1,3-dithiane unit in the C-ring plays a key role in
      the spiroketalization and subsequent epimerization. The synthesis requires 24
      steps, with a longest linear sequence of 19 steps in an overall yield of 14.5%
      (for the longest linear sequence). [reaction: see text]

PMID- 14653682
TI  - Synthesis of the C-1-C-28 ABCD unit of spongistatin 1.
AB  - The synthesis of the C-1-C-28 ABCD fragment of spongistatin is described. Anti
      selective boron-mediated aldol coupling of a CD spiroketal ketone fragment to an
      AB spiroketal aldehyde unit forms the desired C1-C28 advanced intermediate. Other
      features include the double conjugate addition of a dithiol to an ynone to
      generate the key beta-keto-dithiane unit required for the synthesis of the AB
      spiroketal fragment. [reaction: see text]

PMID- 14653683
TI  - Stereochemical models for rh-catalyzed amination reactions of chiral sulfamates.
AB  - Oxidative C-H amination of chiral sulfamate esters using achiral Rh-carboxylate
      catalysts, PhI(OAc)(2), and MgO occurs in high yield and with good to excellent
      diastereocontrol. A number of examples are included to support a proposed
      transition state model that accounts for the observed stereoinduction. In
      addition, stereoselective intramolecular aziridination with substituted homoallyl
      sulfamates is demonstrated and is rationalized through an analogous
      stereochemical construct. [reaction: see text]

PMID- 14653684
TI  - Palladium-catalyzed sequential alkylation-alkenylation reactions: new three
      component coupling leading to oxacycles.
AB  - A new three-component domino reaction catalyzed by palladium was devised,
      producing polysubstituted bicyclic molecules in good yields from readily
      available substrates. The reaction conditions and the scope of the process were
      examined, and a possible mechanism is proposed. [reaction: see text]

PMID- 14653685
TI  - Kinetics of amide and peptide cleavage by alkaline hydrogen peroxide.
AB  - The hydroperoxide anion cleaves unactivated amides and peptides although it is
      completely unreactive toward ethyl esters. The cleavage by HO2(-) proceeds faster
      than by OH(-) and involves additional routes with general acid assistance by H2O2
      and general base assistance by OH(-) and HO2(-). Cleavage of polypeptides occurs
      at the N-terminal peptide bond. [reaction: see text]

PMID- 14653686
TI  - Palladium-catalyzed regioselective arylation of imidazo[1,2-a]pyrimidine.
AB  - Imidazo[1,2-a]pyrimidine can be arylated at the 3-position with aryl bromides in
      the presence of base and a catalytic amount of palladium. This provides an
      efficient one-step synthesis of 3-arylimidazo[1,2-a]pyrimidines from the
      unsubstituted heterocycle. [reaction: see text]

PMID- 14653687
TI  - Sulfo-protected hexosamine monosaccharides: potentially versatile building blocks
      for glycosaminoglycan synthesis.
AB  - 2,2,2-Trifluorodiazoethane was investigated as a reagent for sulfo group
      protection on hexosamine monosaccharides. The synthesis of glucosamine and
      galactosamine building blocks fully differentiated for glycosaminoglycan
      synthesis and the synthesis of glycosyl donors are described. The compatibility
      of trifluoroethylsulfonate under a variety of reaction conditions has also been
      investigated. [structure: see text]

PMID- 14653688
TI  - Intramolecular formal oxa-[3 + 3] cycloaddition approach to the ABD system of
      phomactin A.
AB  - The ABD-ring of phomactin A was synthesized using an intramolecular formal oxa-[3
      + 3] cycloaddion of an alpha,beta-unsaturated iminium salt tethered to a 1,3
      diketone. This represents the first time that the 12-membered ring has been
      formed simultaneously with the 1-oxadecalin and should afford a facile route to
      the challenging structure of phomactin A. [reaction: see text]

PMID- 14653689
TI  - Efficient route to 1,3-Di-N-imidazolylbenzene. A comparison of monodentate vs
      bidentate carbenes in Pd-catalyzed cross coupling.
AB  - A new bis(carbene) ligand architecture has been developed and was evaluated in
      the Suzuki-Miyaura cross-coupling reaction of various aryl halides with
      phenylboronic acid. Several new bis(carbene) ligands were tested in different
      carbene:Pd ratios. Pd(OAc)(2) and Pd(2)(dba)(3) were compared for efficiency as a
      Pd source. It was found that the Pd(OAc)(2)/bis(carbene) system formed a catalyst
      for the activation of chlorobenzene. [reaction: see text]

PMID- 14653690
TI  - Efficient synthesis of substituted vinyl ethers using the Julia olefination.
AB  - Julia olefination between alpha-alkoxy sulfones 2a-c and a wide variety of
      ketones or aldehydes afforded substituted vinyl ethers in 46-90% yields. Sulfones
      2a-c were readily prepared in two steps from commercially available reagents in
      68-80% yields. Optimization revealed that the nature of the base, the solvent,
      and the temperature were crucial to obtaining the desired vinyl ethers.
      [reaction: see text]

PMID- 14653691
TI  - Bivalent transition-state analogue inhibitors of human glyoxalase I.
AB  - A new class of competitive inhibitors of homodimeric human glyoxalase I has been
      created by cross-linking two molecules of the transition-state analogue S-(N-4
      chlorophenyl-N-hydroxycarbamoyl)glutathione (CHG) through their gamma-glutamyl
      NH(2) groups with poly-beta-alanyl tethers of differing length: [CHG(beta
      ala)n](2) suberate diamide (n = 1-7). The strongest inhibitors of this antitumor
      target enzyme likely bind simultaneously to the active site on each subunit to
      give K(i) values as small as 0.96 nM (n = 6). [structure: see text]

PMID- 14653692
TI  - Dramatic enhancement of antagonistic activity on vitamin D receptor: a double
      functionalization of 1alpha-hydroxyvitamin D3 26,23-lactones.
AB  - The synthesis of novel vitamin D receptor antagonists, 24-methyl-1alpha
      hydroxyvitamin D(3) 26,23-lactones, is reported. We found that the biological
      activities of the vitamin D(3) lactones were affected by the structure of the
      lactone part. Furthermore, introduction of a 2alpha-methyl group into the 24
      methylvitamin D(3) lactones dramatically enhanced their anti-vitamin D activity.
      [reaction: see text]

PMID- 14653693
TI  - (S)-(+)-N-acetylphenylglycineboronic acid: a chiral derivatizing agent for Ee
      determination of 1,2-diols.
AB  - A new chiral derivatizing agent for ee determination of 1,2-diols via (1)H NMR is
      described. (S)-(+)-N-acetylphenylglycineboronic acid (1) is synthesized in
      enantiomerically pure form; its reaction with chiral diols quantitatively yields
      cyclic boronic esters 5a-g. The latter show a remarkably high
      diastereodifferentiation of proton NMR signals useful for de determination.
      [reaction: see text]

PMID- 14653694
TI  - Coumarin-4-ylmethoxycarbonyls as phototriggers for alcohols and phenols.
AB  - Caged compounds can be used to regulate the spatial and temporal dynamics of
      signaling molecules in live cells. Photochemical properties of coumarin-4
      ylmethoxy carbonates (1a-d) are investigated to construct caged compounds of
      hydroxy-containing molecules. All the compounds possess desired properties as
      phototriggers for alcohols and phenols. The 6-bromo-7-hydroxycoumarin-4
      ylmethoxycarbonyl (Bhcmoc) group has the highest photochemical efficiency and is
      applied to make caged compounds of 1,2-dioctanoylglycerol (diC(8)), Tyr-OMe, and
      adenosine. [reaction: see text]

PMID- 14653695
TI  - Beyond Schmittel and Myers-Saito cyclizations: rearrangements of 4-heteroatom-1,2
      hexa-diene-5-ynes.
AB  - The thermal rearrangements of 4-heteroatom-1,2-hexadiene-5-ynes (2) were studied
      at the BLYP/6-311+G//BLYP/6-31G level of theory. Cyclization of 2 to heteroatom
      containing cyclopentadienyl structures (6) competes with the Claisen-type
      rearrangement to acyclic, allenic structures. Cyclizations to cyclobutene (4)-
      and cyclohexadiene (8)-derived heterocycles are not feasible as a result of high
      reaction barriers and lower-lying alternative pathways. [structure: see text]

PMID- 14653696
TI  - Ultrafast chemistry: cobalt carbonyl-mediated synthesis of diaryl ketones under
      microwave irradiation.
AB  - By combining the advantages of metal activation, in situ carbon monoxide
      delivery, and microwave heating, benzophenones were efficiently synthesized in 6
      10 s. These ultrafast carbonylation reactions occur under air by flash heating of
      aryl iodides in the presence of dicobalt octacarbonyl. [reaction: see text]

PMID- 14653697
TI  - Enantioselective syntheses of ring-C precursors of vitamin B12. Substrate
      control. A novel Si-assisted elimination of vinyl bromides.
AB  - Homochiral ring-C precursors 34 of Vitamin B(12) have been prepared by Ireland
      Claisen rearrangement of allyl esters 32, followed by a novel Si-assisted
      elimination of HBr. [reaction: see text]

PMID- 14653698
TI  - Different C-glycosidation products of glucal with alkynyl or propargyl silanes
      under acidic conditions.
AB  - Propargylic and acetylenic silyl groups on propyne control the C-glycosidation
      products depending on the trimethylsilyl and triisopropylsilyl groups used. Some
      mechanistic discussions are included. [reaction: see text]

PMID- 14653699
TI  - One-pot synthesis of homoallylic ketones from the addition of vinyl grignard
      reagent to carboxylic esters.
AB  - Fifteen homoallylic ketones have been synthesized in 26-77% yields on treatment
      of aromatic, aliphatic, and alpha-amino methyl carboxylates with excess
      vinylmagnesium bromide and catalytic amounts of a copper salt in THF. Alpha-amino
      homoallylic ketones derived from N-protected alpha-amino esters possessing
      aliphatic and alcohol side chains were synthesized in > or =98% enantiomeric
      purity. [reaction: see text]

PMID- 14653700
TI  - Sequential cross-metathesis/electrophilic fluorodesilylation: a novel entry to
      functionalized allylic fluorides.
AB  - Various allylic fluorides were prepared using a two-step process involving a
      cross-metathesis of allyltrimethylsilane with different olefinic partners
      followed by a fluorodesilylation of the corresponding functionalized allylsilanes
      with Selectfluor. [reaction: see text]

PMID- 14653701
TI  - Introducing transglycosylation activity into human salivary alpha-amylase (HSA).
AB  - Synthesis of 4-nitrophenyl 1-thio-beta-D-maltoside, maltotrioside, and
      maltotetraoside in yields up to 60% has been achieved by a Tyr151Met (Y151M)
      mutant of human salivary alpha-amylase. Y151M is capable of transferring maltose
      and maltotriose residues from a maltotetraose donor onto different p-nitrophenyl
      glycosides. (1)H and (13)C NMR studies revealed that the mutated enzyme preserved
      the stereo- and regioselectivity. The glycosylation took place at position 4 of
      the glycosyl acceptor, forming the alpha(1-4)glycosidic bond, exclusively.
      [reaction: see text]

PMID- 14653702
TI  - Enantioselective synthesis of cyclic secondary amines through Mo-catalyzed
      asymmetric ring-closing metathesis (ARCM).
AB  - Carbocyclic amines are synthesized efficiently in up to 93% ee by asymmetric ring
      closing metathesis (ARCM) with 2-5 mol % chiral Mo complexes. An example is
      provided where the catalyst is prepared in situ (catalyst isolation not needed)
      to afford secondary amines that cannot be prepared by alternative methods.
      [reaction: see text]

PMID- 14653703
TI  - Cyclization of oxa-bicyclic alkenes with beta-iodo-(Z)-propenoates and o
      iodobenzoate catalyzed by nickel complexes: a simple efficient route to annulated
      coumarins.
AB  - In the presence of Ni(dppe)Br(2) and Zn powder in acetonitrile at 80 degrees C,
      oxa-bicyclic olefins undergo cyclization with o-iodobenzoate and with beta-iodo
      (Z)-propenoates to give the benzocoumarin derivatives in moderate to good yields.
      This methodology offers a simple efficient way for the synthesis of structurally
      complicate coumarins in one pot. [reaction: see text]

PMID- 14653704
TI  - New approach for the synthesis of isoxazoline-N-oxides.
AB  - A strategy for the synthesis of isoxazoline-N-oxides (cyclic five-membered
      nitronates) from primary nitro compounds and olefins is described. The key step
      of the process involves 1,3-dipolar cycloaddition of corresponding 1-bromosilyl
      nitronates with alkenes. [reaction: see text]

PMID- 14653705
TI  - Synthesis of the polycyclic ring systems of artocarpol A and D.
AB  - The first synthesis of the polycyclic ring systems of artocarpol A and D has been
      accomplished. These natural products were isolated recently from the root bark of
      Artocarpus rigida, and artocarpol A has been shown to have potent
      antiinflammatory properties. The synthesis of an artocarpol D analogue was
      achieved on condensation of 11H-dibenzo[b,f]oxepin-10-one with senecialdehyde.
      The reaction of this oxepinone with citral afforded a 2H-pyran that on subsequent
      irradiation afforded an analogue of artocarpol A. [reaction: see text]

PMID- 14653706
TI  - Microwave-assisted [3 + 2] cycloadditions of azomethine ylides.
AB  - The microwave-assisted intramolecular [3 + 2] cycloaddition reaction of
      azomethine ylides to activated and nonactivated alkenes and alkynes is described.
      The procedure allows the synthesis of pyrrolidines and pyrrole products in good
      to excellent overall yields in short reaction times. It appears from parallel
      comparative studies that the microwave procedure favors the reaction times and
      overall purity of the crude reaction mixture. The reactions can also be performed
      in the absence of solvent. [reaction: see text]

PMID- 14653707
TI  - Spectroscopic analysis of liquid/liquid interfaces in multiphase microflows.
AB  - Microscopic quasi-elastic laser scattering (muQELS) spectroscopy has been
      developed for analysis of interfacial phenomena at laminar multiphase microflow
      in a microchannel. Transport phenomena of a metal chelate through a water/toluene
      interface were measured, and transient adsorption of the chelate in the initial
      step of the transport was measured. A water/methanol miscible interface was also
      measured, and the interfacial free energy of a miscible interface was determined
      for the first time. The muQELS is expected to be very effective not only for
      physicochemical investigations of transport and mixing, but also for elemental
      process analysis of heterogeneous reactions.

PMID- 14653708
TI  - Deformation of porous molecular networks induced by the exchange of guests in
      single crystals.
AB  - A strategy for making molecular networks that are porous and deformable is
      revealed by the behavior of compound 1, in which groups that form hydrogen bonds
      are attached to a nominally tetrahedral Si core. Compound 1 crystallizes from
      various carboxylic acids to produce a porous hydrogen-bonded diamondoid network,
      with up to 65% of the volume available for including guests. Changing the guests
      expands or contracts the network up to 30% in one direction, and single crystals
      can accommodate these exchange-induced deformations without loss of
      crystallinity. This resilience appears to result in part from the incorporation
      of flexible Si nodes in an otherwise robust network maintained by multiple
      hydrogen bonds. In certain cases, exchange is faster than deformation of the
      network, allowing the isolation of metastable structures with a new guest
      included in an otherwise unchanged network. Such processes can provide new
      materials that would be difficult or impossible to obtain in other ways.

PMID- 14653710
TI  - Synthesis of very small TiO2 nanocrystals in a room-temperature ionic liquid and
      their self-assembly toward mesoporous spherical aggregates.
AB  - In this Communication, we describe the synthesis of 2-3 nm sized titania
      nanocrystals in a room-temperature ionic liquid under mild conditions and their
      self-assembly toward mesoporous TiO2 spheres. The resulting structures combine
      the convenient handling of larger spheres with a considerable high surface area
      and narrow pore size distribution and are expected to have potential in solar
      energy conversion, catalysis, and optoelectronic devices.

PMID- 14653709
TI  - Frozen-solution conformational analysis by REDOR spectroscopy.
AB  - Frozen-solution conformational analysis (FrSCA) can be performed on organic
      compounds using REDOR spectroscopy. REDOR measurements on frozen aqueous
      solutions of 13C-methyl beta-15N-aminoglucoside indicate a bimodal distribution
      of conformations in a 68:32 ratio, with 13C-15N distances of 4.31 and 3.55 A,
      respectively. The high resolution and straightforward sample preparation make
      FrSCA an attractive alternative to solution-based NMR methods of conformational
      analysis.

PMID- 14653711
TI  - Quaternary self-organization of porphyrin and fullerene units by clusterization
      with gold nanoparticles on SnO2 electrodes for organic solar cells.
AB  - Novel organic solar cells prepared using quaternary self-organization of
      porphyrin (donor) and fullerene (acceptor) dye units by clusterization with gold
      nanoparticles on SnO2 electrodes exhibit the remarkable enhancement of the
      photoelectrochemical properties relative to the reference systems.

PMID- 14653712
TI  - In situ scanning tunneling microscopy of DNA-modified gold surfaces: bias and
      mismatch dependence.
AB  - In situ scanning tunneling microscopy has been performed on DNA-modified gold
      surfaces under physiological conditions. The STM images of DNA-modified gold
      surfaces are strongly dependent on the applied potential and percentage of DNA
      duplexes containing a single base mismatch. At negative surface potentials we
      observe reproducible features that are attributed to DNA agglomerates where the
      DNA duplexes are in the upright orientation; at positive potentials, when DNA
      molecules lie down on the surface, the film is transparent, and only the gold
      surface is distinguishable. These observations indicate that DNA possesses a non
      negligible local density of states which can be probed when the DNA duplex is in
      the upright orientation. By varying the percentage of DNA duplexes containing a
      single base mismatch, we have observed a dramatic change in the image contrast as
      a result of the perturbation induced by the mismatch on the electronic pathway
      inside the DNA. These results emphasize the central role of the integrity of the
      pi-stack for DNA charge transport. Duplex DNA is a promising candidate in
      molecular electronics, but only in arrangements where the orbitals can
      efficiently overlap with the electronic states of the electrodes and the
      environment does not constrain the DNA in non-native, poorly stacked
      conformations.

PMID- 14653713
TI  - Lipid/protein interactions and the membrane/water interfacial region.
AB  - Despite the importance of lipid/protein interactions in the folding, assembly,
      stability, and function of membrane proteins, information at an atomic level on
      how such proteins interact with the lipids that surround them remains sparse. The
      dynamics and flexible nature of the protein/bilayer interaction make it difficult
      to study, for example, by crystallographic means. However, based on recent
      progress in molecular simulations of membranes it is possible to address this
      problem computationally. This communication reports one of the first attempts to
      use multiple ns molecular simulations to establish a qualitative picture of the
      intermolecular interactions between the lipids of a bilayer and two topologically
      different membrane proteins for which a high resolution (2 A or better) X-ray
      structure is available.

PMID- 14653714
TI  - Bias-dependent visualization of electron donor (D) and electron acceptor (A)
      moieties in a chiral DAD triad molecule.
AB  - The 2D crystal lattice structure and bias-dependent contrast of a chiral electron
      donor-acceptor-donor triad system, composed of two oligo(p-phenylene vinylene)
      electron donors and a perylenediimide electron acceptor (OPV4-PDI-OPV4), have
      been studied by means of scanning tunneling microscopy (STM) at the liquid
      graphite interface. OPV4-PDI-OPV4 is ordered in rows and forms a well-ordered 2D
      crystal lattice structure. The electrical properties of the donor and acceptor
      parts are distinguished by the contrast in bias-dependent STM imaging.

PMID- 14653715
TI  - Induced protein dimerization in vivo through covalent labeling.
AB  - We present here a novel approach to induce protein dimerization in living cells
      through covalent labeling of fusion proteins with ligands which are interacting
      with other proteins. The covalent labeling is based on the reaction of the DNA
      repair protein O6-alkylguanine-DNA alkyltransferase with O6-benzylguanine coupled
      to an appropriate ligand. Using methotrexate as a ligand, it is shown that the
      approach can be used to control transcription in the yeast Saccharomyces
      cerevisiae. The specificity of the labeling reaction and its irreversible nature
      should allow the approach to become a valuable tool to study and control protein
      dimerization in vivo.

PMID- 14653716
TI  - Self-assembled nanotubes that reversibly bind acetic acid guests.
AB  - A large bis-urea macrocycle was synthesized and assembled into columnar nanotubes
      containing a sizable cavity. This purely organic nanotube is held together
      primarily by hydrogen bonding and yet shows remarkable thermal stability up to
      180 degrees C in the presence and absence of acetic acid guest. This enables the
      nanotube to be used as reusable organic zeolite.

PMID- 14653717
TI  - Photochemical charge transfer and trapping at the interface between an organic
      adlayer and an oxide semiconductor.
AB  - Identification of charge transfer and trapping sites on semiconducting oxide
      surfaces is of fundamental importance in furthering the field of heterogeneous
      photocatalysts. Using scanning tunneling microscopy, electron energy loss
      spectroscopy, and photodesorption, we observed both electron trapping and hole
      transfer events on the (110) surface of TiO2 rutile. UV irradiation of a
      saturated monolayer of trimethyl acetate (TMA) on TiO2(110) at room temperature
      resulted in hole transfer to the carboxylate group, followed by (CH3)3C-COO bond
      cleavage and desorption of CO2 and isobutene/isobutane. Hole transfer to TMA
      proceeded in the absence of a gas-phase electron scavenger (which is typically
      O2) because the accompanying photogenerated electrons could be trapped at the
      surface as Ti3+ cations bound to bridging OH groups. The extent of electron
      trapping, gauged by electron spectroscopy, correlated directly with the yields of
      photodesorption fragments resulting from the hole transfer channel. Charge at the
      Ti3+ sites was titrated in the dark via a reaction between O2 and the Ti3+-OH
      groups.

PMID- 14653718
TI  - Two-dimensional self-organization of phthalocyanine and porphyrin: dependence on
      the crystallographic orientation of Au.
AB  - By immersing Au substrate into a benzene solution containing both cobalt(II)
      phthalocyanine (CoPc) and copper(II) tetraphenyl-21H,23H-porphine (CuTPP), a two
      dimensional alternate bimolecular structure was formed on the reconstructed
      Au(100)-(hex) surface.

PMID- 14653719
TI  - New routes to the detection of relaxation allowed coherence transfer in
      paramagnetic molecules.
AB  - A new pulse sequence is proposed to measure cross correlation rates between 1H
      Curie spin relaxation and 1H-15N or 1H-13C dipole-dipole coupling
      (%@mt;sys@%Gamma%@sx@%H,HX%@be@%CS,DD%@sxx@%%@mx@% ) in paramagnetic systems. The
      new sequence has been conceived to obtain quantitative measurements of cross
      correlation rates in the close proximity to the paramagnetic center, preventing
      the loss of information due to fast transverse relaxation. The approach was
      tested on the dicalcium protein calbindin D9k in which Ca2+ has been substituted
      at site II with Ce3+. At variance with previously reported experiments, all peaks
      observed in HSQC experiments tailored to paramagnetic signals give quantitative
      estimates of
      %@mt;sys@%Gamma%@sx@%H%@ital@%,%@rsf@%HX%@be@%CS%@ital@%,%@rsf@%DD%@sxx@%%@mx@% .
      This is crucial to refine the immediate proximity of the metal ion.

PMID- 14653720
TI  - Rhenium-promoted diastereo- and enantioselective cyclopentannulation reactions:
      furans as 1,3-propene dipoles.
AB  - The rhenium furan complexes TpRe(CO)(MeIm)(eta2-2-methylfuran) (1) and
      TpRe(CO)(MeIm)(eta2-2,5-dmethylfuran) (2) undergo Lewis acid-promoted
      cyclopentannulation reactions with enones and enals to generate 3
      acetylcyclopentene complexes. During the reaction, a rearrangement occurs such
      that the alpha and beta carbons of the enone are incorporated into the new
      carbocycle. Treatment of these complexes with an oxidant (H2O2 or silver
      triflate) liberates the acetylcyclopentene. When a resolved form of the rhenium
      complex is used, the acetylcyclopentenes can be obtained enantioselectively.

PMID- 14653721
TI  - Constraining asymmetric organometallic catalysts within mesoporous supports
      boosts their enantioselectivity.
AB  - By constraining tethered asymmetric organometallic catalysts within the nanopores
      of silica supports so as to increase the interaction between the pore wall and
      the active center (and hence to restrict access of the reactant to the catalyst),
      a significant improvement in enantioselectivity is achieved. A schematic
      illustration of a cationic chiral, organometallic catalyst, [Rh(I)(COD)PMP] {(S)
      (+)-1-(2-pyrrolidinylmethyl)-pyrrolidine and cyclooctadiene}, which is
      noncovalently anchored via a N-H...F hydrogen bond with the triflate ion, CF3SO3
      , to the curved inner surface of a 38 A diameter pore of a silica support for the
      asymmetric hydrogenation of the C=O bond in methyl benzoylformate to the
      corresponding methyl mandelate is shown. Rh (purple); N (blue); H (white); F
      (green); C (gray); S (yellow); O (red).

PMID- 14653722
TI  - Metal-centered photoinduced electron transfer reduction of a gold(III) porphyrin
      cation linked with a zinc porphyrin to produce a long-lived charge-separated
      state in nonpolar solvents.
AB  - Photoexcitation of an electron donor-acceptor linked dyad containing gold(III)
      and zinc(II) porphyrins (ZnPQ-AuIIIPQ+) results in electron transfer from the
      singlet excited state of ZnPQ to the metal center of AuPQ+ to produce the charge
      separated state (ZnPQ*+-AuIIPQ) which has a long lifetime (10 mus) in nonpolar
      solvents such as cyclohexane and toluene.

PMID- 14653723
TI  - Replication of vertical features smaller than 2 nm by soft lithography.
AB  - This communication demonstrates a simple, soft lithographic approach to the
      replication and metrology of nanoscale vertical displacements. We patterned test
      structures with regular patterns that minimize artifacts in measurements by
      atomic force microscopy. A composite stamp of poly(dimethylsiloxane) (PDMS)
      molded against the original test structure served as a template to generate
      polyurethane replicas. We replicated vertical displacements down to approximately
      1.5 nm. This replication demonstrates the capability of soft lithography to
      reproduce features with dimensions similar to those of large molecules.

PMID- 14653724
TI  - Pulsed ELDOR spectroscopy measures the distance between the two tyrosyl dadicals
      in the R2 subunit of the E. coli ribonucleotide reductase.
AB  - Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of
      nucleoside diphosphates (NDPs) to deoxynucleoside diphosphates (dNDPs). This RNR
      is composed of two homodimeric subunits: R1 and R2. R1 binds the NDPs in the
      active site, and R2 harbors the essential di-iron tyrosyl radical (Y*) cofactor.
      In this paper, we used PELDOR, a method that detects weak electron-electron
      dipolar coupling, to make the first direct measurement of the distance between
      the two Y*'s on each monomer of R2. In the crystal structure of R2, the Y*'s are
      reduced to tyrosines, and consequently R2 is inactive. In R2, where the Y*'s
      assume a well-defined geometry with respect to the protein backbone, the PELDOR
      method allows measurement of a distance of 33.1 +/- 0.2 A that compares favorably
      to the distance (32.4 A) between the center of mass of the spin density
      distribution of each Y* on each R2 monomer from the structure. The experiments
      provide the first direct experimental evidence for two Y*'s in a single R2 in
      solution.

PMID- 14653725
TI  - C5-methylation of cytosine in B-DNA thermodynamically and kinetically stabilizes
      BI.
AB  - We have examined the backbone dynamics of two alternating purine-pyrimidine
      dodecamers. One sequence consists of "pure" GC bases; the other one contains 5
      methylcytosines. The effect of the methyl groups on the backbone substates BI/BII
      was investigated by means of molecular dynamics. The methylation influences, on
      one hand, the transition barrier between BI and BII and, on the other hand, the
      state of equilibrium. The kinetic consequences are an increase of the DeltaG of
      Gp5mC steps by 1.5 kcal/mol and a decrease of the DeltaG of 5mCpG steps by 0.8
      kcal/mol (compared with the nonmethylated DNA). Thus, the additive group
      differentiates between the two occurring dinucleotide steps and renders the
      phosphate of the 5-methylcytosine more rigid, as proposed by experimental
      studies. The thermodynamic consequences are an increase of the DeltaG of Gp5mC
      steps by 1.1 kcal/mol and a decrease of the DeltaG of 5mCpG steps by 0.8
      kcal/mol. The reason for this shift in equilibrium is still not completely clear
      on a molecular basis. But we can conclude that the indirect readout of DNA is
      influenced by methylation.

PMID- 14653726
TI  - Asymmetric intermolecular Pauson-Khand reactions of unstrained olefins: the (o
      dimethylamino)phenylsulfinyl group as an efficient chiral auxiliary.
AB  - The first asymmetric version of intermolecular Pauson-Khand reactions of
      unstrained alkenes is described. Generally simple acyclic alkenes exhibit low
      reactivity and regioselectivity in intermolecular Pauson-Khand reactions;
      however, o-(dimethylamino)phenyl vinyl sulfoxide reacts under very mild
      conditions with a wide variety of terminal alkynes in a completely regioselective
      and highly stereoselective manner. The utility of the resulting 5-sulfinyl-2
      cyclopentenones in asymmetric synthesis is illustrated by a very short
      enantioselective synthesis of the antibiotic (-)-pentenomycin I.

PMID- 14653727
TI  - Dynamic interfaces between cells and surfaces: electroactive substrates that
      sequentially release and attach cells.
AB  - An electroactive substrate that combines dual dynamic properties is demonstrated.
      A monolayer is patterned to first release an immobilized ligand, and therefore
      adherent cells, on application of an electrical potential. Subsequently,
      electrical oxidation of the substrate results in immobilization of ligands, and
      migration of adherent cells.

PMID- 14653728
TI  - Control over the wettability of an aligned carbon nanotube film.
AB  - Three-dimensional anisotropic aligned carbon nanotube microstructures were
      constructed by the chemical vapor deposition method on silicon templates with
      well-defined structure. It brought about new properties of wettability.
      Superhydrophobic (contact angle > 150 degrees ) and very hydrophilic (contact
      angle < 30 degrees ) properties can both be achieved by a simple change of
      structural parameter.

PMID- 14653729
TI  - Epitaxial electrodeposition of Prussian blue thin films on single-crystal
      Au(110).
AB  - Epitaxial Prussian blue (PB) films are deposited electrochemically onto a Au(110)
      substrate. High-resolution X-ray diffraction shows that the PB films have a [111]
      out-of-plane orientation. The very large lattice mismatch of 148% is reduced to
      about 1% by the formation of (1 x 2)PB(111)[onemacr;10]//(6 x
      5)Au(110)[onemacr;10] and (1 x 2)PB(111)[01onemacr;]//(6 x 5)Au(110)[onemacr;10]
      epitaxial relationships. Peaks in the cyclic voltammogram of PB on Au(110) are
      sharper than those on polycrystalline Au, consistent with higher structural order
      and a single out-of-plane orientation. The development of epitaxial films of PB
      and PB analogues will allow the measurement of the orientation-dependent
      properties of these molecular magnets. It will also open the door to the
      development of novel molecular spintronic devices, such as those which exhibit
      spin-dependent electron transfer.

PMID- 14653730
TI  - The total synthesis of (--)-lemonomycin.
AB  - The first total synthesis of the novel glycosylated tetrahydroisoquinoline
      antitumor antibiotic (-)-lemonomycin has been accomplished (15 steps from 9). The
      highly convergent synthesis relies on a key asymmetric dipolar cycloaddition to
      set the stereochemistry of the aglycone core, a Suzuki fragment coupling to
      connect the diazabicycle to the aryl subunit, and a stereoselective Pictet
      Spengler reaction that incorporates the aminoglycoside subunit directly into the
      core structure without the need for late-stage glycosylation or protecting group
      manipulations. The novel aminoglycoside was prepared using a highly
      diastereoselective Felkin-controlled acetate aldol addition reaction to a
      threonine-derived ketone.

PMID- 14653731
TI  - An examination of metal-ligand binding modes in rubidium diphenylmethanide.
AB  - A powerful new synthetic method allows for the exploration of an interesting
      class of rubidium diphenylmethanides showing different solid-state modifications
      depending on the crystallization temperatures. Theoretical and structural
      analysis in the solution and the solid state leads to a broader understanding of
      metal-ligand binding modes.

PMID- 14653732
TI  - Aromatic hydroxylation by cytochrome P450: model calculations of mechanism and
      substituent effects.
AB  - The mechanism and selectivity of aromatic hydroxylation by cytochrome P450
      enzymes is explored using new B3LYP density functional theory computations. The
      calculations, using a realistic porphyrin model system, show that rate
      determining addition of compound I to an aromatic carbon atom proceeds via a
      transition state with partial radical and cationic character. Reactivity is shown
      to depend strongly on ring substituents, with both electron-withdrawing and 
      donating groups strongly decreasing the addition barrier in the para position,
      and it is shown that the calculated barrier heights can be reproduced by a new
      dual-parameter equation based on radical and cationic Hammett sigma parameters.

PMID- 14653733
TI  - The synthesis of phosphaisocoumarins by Cu(I)-catalyzed intramolecular
      cyclization of o-ethynylphenylphosphonic acid monoesters.
AB  - Cu(I)-catalyzed intramolecular cyclization of o-ethynylphenylphosphonic acid
      monoethyl esters was examined, and a new class of six-membered phosphorus
      heterocycles was formed with high regioselectivity and good yields. The present
      reaction is the first example of intramolecular addition of P-OH to alkynes,
      which provides a convenient way to synthesize novel phosphorus heterocycles
      having potential bioactivities.

PMID- 14653734
TI  - Beta-deuterium isotope effects on amine basicity, "inductive" and stereochemical.
AB  - Secondary beta deuterium isotope effects on acidity constants of ammonium ions
      are measured using a remarkably precise NMR titration method. Deuteration is
      found to increase the basicity of methylamine, dimethylamine, benzylamine, and
      N,N-dimethylaniline. The effect is attributed to a lowered zero-point energy of a
      CH bond adjacent to an amine nitrogen. The method permits a determination of the
      stereochemical dependence of the isotope effect in a locked piperidine, and it is
      found that deuteration is more effective when antiperiplanar to a lone pair. The
      values are consistent with a cos(2) dependence on dihedral angle, with no
      detectable angle-independent inductive effect.

PMID- 14653735
TI  - Oxygen activation and electron transfer in flavocytochrome P450 BM3.
AB  - In flavocytochrome P450 BM3, there is a conserved phenylalanine residue at
      position 393 (Phe393), close to Cys400, the thiolate ligand to the heme.
      Substitution of Phe393 by Ala, His, Tyr, and Trp has allowed us to modulate the
      reduction potential of the heme, while retaining the structural integrity of the
      enzyme's active site. Substrate binding triggers electron transfer in P450 BM3 by
      inducing a shift from a low- to high-spin ferric heme and a 140 mV increase in
      the heme reduction potential. Kinetic analysis of the mutants indicated that the
      spin-state shift alone accelerates the rate of heme reduction (the rate
      determining step for overall catalysis) by 200-fold and that the concomitant
      shift in reduction potential is only responsible for a modest 2-fold rate
      enhancement. The second step in the P450 catalytic cycle involves binding of
      dioxygen to the ferrous heme. The stabilities of the oxy-ferrous complexes in the
      mutant enzymes were also analyzed using stopped-flow kinetics. These were found
      to be surprisingly stable, decaying to superoxide and ferric heme at rates of
      0.01-0.5 s(-)(1). The stability of the oxy-ferrous complexes was greater for
      mutants with higher reduction potentials, which had lower catalytic turnover
      rates but faster heme reduction rates. The catalytic rate-determining step of
      these enzymes can no longer be the initial heme reduction event but is likely to
      be either reduction of the stabilized oxy-ferrous complex, i.e., the second
      flavin to heme electron transfer or a subsequent protonation event. Modulating
      the reduction potential of P450 BM3 appears to tune the two steps in opposite
      directions; the potential of the wild-type enzyme appears to be optimized to
      maximize the overall rate of turnover. The dependence of the visible absorption
      spectrum of the oxy-ferrous complex on the heme reduction potential is also
      discussed.

PMID- 14653737
TI  - What is so special about Arg 55 in the catalysis of cyclophilin A? insights from
      hybrid QM/MM simulations.
AB  - Potential of mean force (PMF) simulations with a hybrid QM/MM potential function
      were used to analyze the catalytic mechanism of human cyclophilin A (CypA). PMF
      calculations were performed for proline isomerization of peptides in solution,
      the wild-type CypA, and several CypA mutants. With an approximate density
      functional theory, the self-consistent-charge density functional tight binding
      (SCC-DFTB) as the QM level, and CHARMM 22 force field as MM, satisfactory
      energetics compared to available experiments were obtained. Calculations for the
      Arg55Ala and zero-charge-Arg55 mutants clearly indicated that Arg 55
      significantly stabilizes the isomerization transition state through electrostatic
      interactions. However, the decrease in the average distance (thus the increase in
      interaction) between Arg 55 and the substrate amide N in going from the stable
      states to the transition state is mainly due to the pyramidalization of the amide
      N rather than motions associated with Arg 55. Although the nanosecond simulations
      cannot exclude the existence of sub-millisecond collective motions proposed on
      the basis of recent elegant NMR relaxation and line-shape analyses, the
      energetics obtained for the various enzyme systems here indicate that the
      contribution from motions of active site residues to catalysis is expected to be
      small. Instead, the present simulations support that the structural stability
      rather than mobility of the preorganized active site is more important. Through
      hydrogen-bonding interactions among the substrate, Arg 55, Gln 63, and Asn 102,
      the active site of the wild-type enzyme is structurally very stable and puts Arg
      55 in a favorable position to perform its catalytic role in the transition state.
      This is further illustrated with the somewhat unexpected prediction that Arg55Lys
      is largely catalytically inactive, because Lys does not have the unique
      bifurcating construct of the guanidino group in Arg and thus the active site of
      Arg55Lys cannot accommodate Lys in a position capable of providing electrostatic
      stabilization of the isomerization transition state. Among all the enzyme systems
      studied, the wild-type CypA is the only one that selects the syn/exo transition
      state, while the syn/endo conformation is also present in the mutants, which is
      another reason for their higher barriers. Finally, the present analysis indicated
      that the population of near-attack-conformations (NAC) is not relevant to
      catalysis in CypA.

PMID- 14653738
TI  - Crystal structures of two complexes of the rare-earth-DOTA-binding antibody
      2D12.5: ligand generality from a chiral system.
AB  - We report the crystal structures of antibody 2D12.5 Fab bound to an yttrium-DOTA
      analogue and separately to a gadolinium-DOTA analogue. The rare earth elements
      have many useful properties as probes, and 2D12.5 binds the DOTA (1,4,7,10
      tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid) complexes of all of them
      (Corneillie et al. J. Am. Chem. Soc. 2003, 125, 3436-3437). The structures show
      that there are no direct protein-metal interactions: a bridging water acts as a
      link between the protein and metal, with the chelate present as the M isomer in
      each case. DOTA forms an amphipathic cylinder with the charged carboxylate groups
      toward the face of the chelate near the metal ion, while nonpolar methylene
      groups from the macrocycle and the carboxymethyl groups occupy the rear and sides
      of the molecule. The orientation of the metal-DOTA in the 2D12.5 complex places
      most of the methylene carbon atoms of DOTA in hydrophobic contact with aromatic
      protein side chains. Other binding interactions between the metal complex and the
      antibody include a bidentate salt bridge, four direct H-bonds, and four to five
      water-mediated H-bonds. We find that 2D12.5 exhibits enantiomeric binding
      generality, binding yttrium chelates in both Lambda(deltadeltadeltadelta) and
      Delta(lambdalambdalambdalambda) configurations with modestly different
      affinities. This develops from the symmetrical nature of the DOTA chelate, which
      places heteroatoms and hydrophobic atoms in approximately the same relative
      positions regardless of the helicity of DOTA.

PMID- 14653736
TI  - Two-repeat human telomeric d(TAGGGTTAGGGT) sequence forms interconverting
      parallel and antiparallel G-quadruplexes in solution: distinct topologies,
      thermodynamic properties, and folding/unfolding kinetics.
AB  - We demonstrate by NMR that the two-repeat human telomeric sequence
      d(TAGGGTTAGGGT) can form both parallel and antiparallel G-quadruplex structures
      in K(+)-containing solution. Both structures are dimeric G-quadruplexes involving
      three stacked G-tetrads. The sequence d(TAGGGUTAGGGT), containing a single
      thymine-to-uracil substitution at position 6, formed a predominantly parallel
      dimeric G-quadruplex with double-chain-reversal loops; the structure was
      symmetric, and all guanines were anti. Another modified sequence,
      d(UAGGGT(Br)UAGGGT), formed a predominantly antiparallel dimeric G-quadruplex
      with edgewise loops; the structure was asymmetric with six syn guanines and six
      anti guanines. The two structures can coexist and interconvert in solution. For
      the latter sequence, the antiparallel form is more favorable at low temperatures
      (<50 degrees C), while the parallel form is more favorable at higher
      temperatures; at temperatures lower than 40 degrees C, the antiparallel G
      quadruplex folds faster but unfolds slower than the parallel G-quadruplex.

PMID- 14653740
TI  - Preparation and pH triggered inversion of vesicles from poly(acrylic acid)-block
      polystyrene-block-poly(4-vinyl pyridine).
AB  - The aggregate morphologies of the biamphiphilic triblock PAA(26)-b-PS(890)-b
      P4VP(40) have been studied by TEM as a function of pH in DMF/THF/H(2)O mixtures.
      The outside surfaces of the aggregates were characterized by zeta potential
      measurements. Starting at the apparent pH (pH) of 1, and increasing gradually to
      pH14, the aggregate morphologies of this triblock change progressively from
      vesicles (pH1), to solid spherical or ellipsoidal aggregates (pH3 approximately
      11), and finally back to vesicles (pH14). Vesicles prepared at pH1 contain P4VP
      chains on the outside and PAA chains on the inside, while those prepared from the
      same triblock at pH14 contain PAA outside and P4VP inside. The segregation is
      based on the difference in repulsive interactions within the PAA or P4VP corona
      under different pH conditions. At low pH, the curvature is stabilized through
      increased repulsive interactions between the P4VP chains on the outside relative
      to the less repulsive interactions between the PAA chains on the inside. At pH14,
      by contrast, the PAA is preferentially segregated to the outside and the P4VP to
      the inside because of the increased repulsive interaction between PAA chains and
      the decreased repulsive interaction between P4VP chains at high pH. Most
      importantly, vesicles with PAA on the outside can be inverted to P4VP on the
      outside by changing the pH while the vesicles have swollen cores and are under
      dynamic conditions. The conversion mechanism is suggested to involve a whole
      vesicle process because the CMC is far too low for single chain reassembly to be
      involved.

PMID- 14653739
TI  - Mechanism of the glutathione transferase-catalyzed conversion of antitumor 2
      crotonyloxymethyl-2-cycloalkenones to GSH adducts.
AB  - Human glutathione (GSH) transferase (hGSTP1-1) processes with similar kinetic
      efficiencies the antitumor agents 2-crotonyloxymethyl-2-cyclohexenone (COMC-6), 2
      crotonyloxymethyl-2-cycloheptenone (COMC-7), and 2-crotonyloxymethyl-2
      cyclopentenone (COMC-5) to 2-glutathionylmethyl-2-cyclohexenone, 2
      glutathionylmethyl-3-glutathionyl-2-cycloheptenone, and 2-glutathionylmethyl-2
      cyclopentenone, respectively. This process likely involves initial enzyme
      catalyzed Michael addition of GSH to the COMC derivative to give a
      glutathionylated enol(ate), which undergoes nonstereospecific ketonization,
      either while bound to the active site or free in solution, to a glutathionylated
      exocyclic enone. Free in solution, GSH reacts at the exomethylene carbon of the
      exocyclic enone, displacing the first GSH to give the final product. This
      mechanism is supported by the observation of multiphasic kinetics in the presence
      of high concentrations of hGSTP1-1 and the ability to trap kinetically competent
      exocyclic enones in aqueous acid using COMC-6 and COMC-7 as substrates. That the
      exocyclic enone is formed by nonstereospecific ketonization of an enol(ate)
      species is indicated by the observation that COMC-6 (chirally labeled with
      deuterium at the exomethylene carbon) gives stereorandomly labeled exocyclic
      enone. The isozymes hGSTP1-1, hGSTA1-1, hGSTA4-4, and hGSTM2-2 catalyze the
      conversion of COMC-6 to final product with similar efficiencies (K(m) = 0.08-0.34
      mM, k(cat) = 1.5-6.1 s(-)(1)); no activity was detected with the rat rGSTT2-2
      isozyme. Molecular docking studies indicate that in hGSTP1-1, the hydroxyl group
      of Tyr108 might serve as a general acid catalyst during substrate turnover. The
      possible significance of these observations with respect to the metabolism of
      COMC derivatives in multidrug resistant tumors is discussed.

PMID- 14653741
TI  - Probing the role of the C-H...O hydrogen bond stabilized polypeptide chain
      reversal at the C-terminus of designed peptide helices. Structural
      characterization of three decapeptides.
AB  - The structural characterization in crystals of three designed decapeptides
      containing a double d-segment at the C-terminus is described. The crystal
      structures of the peptides Boc-Leu-Aib-Val-Xxx-Leu-Aib-Val-(D)Ala-(D)Leu-Aib-OMe,
      (Xxx = Gly 2, (D)Ala 3, Aib 4) have been determined and compared with those
      reported earlier for peptide 1 (Xxx = Ala) and the all l analogue Boc-Leu-Aib-Val
      Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe, which yielded a perfect right-handed alpha
      helical structure. Peptides 1 and 2 reveal a right-handed helical segment
      spanning residues 1 to 7, ending in a Schellman motif with (D)Ala(8) functioning
      as the terminating residue. Polypeptide chain reversal occurs at residue 9, a
      novel feature that appears to be the consequence of a C-H.O hydrogen bond between
      residue 4 C(alpha)H and residue 9 CO groups. The structures of peptides 3 and 4,
      which lack the pro R hydrogen at the C(alpha) atom of residue 4, are dramatically
      different. Peptide 3 adopts a right-handed helical conformation over the 1 to 7
      segment. Residues 8 and 9 adopt alpha(L) conformations forming a C-terminus type
      I' beta-turn, corresponding to an incipient left-handed twist of the polypeptide
      chain. In peptide 4, helix termination occurs at Aib(6), with residues 6 to 9
      forming a left-handed helix, resulting in a structure that accommodates direct
      fusion of two helical segments of opposite twist. Peptides 3 and 4 provide
      examples of chiral residues occurring in the less favored sense of helical twist;
      (D)Ala(4) in peptide 3 adopts an alpha(R) conformation, while (L)Val(7) in 4
      adopts an alpha(L) conformation. The structural comparison of the decapeptides
      reported here provides evidence for the role of specific C-H.O hydrogen bonds in
      stabilizing chain reversals at helix termini, which may be relevant in aligning
      contiguous helical and strand segments in polypeptide structures.

PMID- 14653742
TI  - Increased speed of rotation for the smallest light-driven molecular motor.
AB  - In this paper we present the smallest artificial light-driven molecular motor
      consisting of only 28 carbon and 24 hydrogen atoms. The concept of controlling
      directionality of rotary movement at the molecular level by introduction of a
      stereogenic center next to the central olefinic bond of a sterically overcrowded
      alkene does not only hold for molecular motors with six-membered rings, but is
      also applicable to achieve the unidirectional movement for molecular motors
      having five-membered rings. Although X-ray analyses show that the five-membered
      rings in the cis- and trans-isomer of the new molecular motor are nearly flat,
      the energy differences between the (pseudo-)diaxial and (pseudo-)diequatorial
      conformations of the methyl substituents in both isomers are still large enough
      to direct the rotation of one-half of the molecule with respect to the other half
      in a clockwise fashion. The full rotary cycle comprises four consecutive steps:
      two photochemical isomerizations each followed by a thermal helix inversion. Both
      photochemical cis-trans isomerizations proceed with a preference for the unstable
      diequatorial isomers over the stable diaxial isomers. The thermal barriers for
      helix inversion of this motor molecule have decreased dramatically compared to
      its six-membered ring analogue, the half-life of the fastest step being only 18 s
      at room temperature.

PMID- 14653743
TI  - Is a small number of charge neutralizations sufficient to bend nucleosome core
      DNA onto its superhelical ramp?
AB  - X-ray diffraction structures of the nucleosome core particle along with a variety
      of experiments are consistent with the idea that an important source of the free
      energy holding DNA to the superhelical ramp on the histone octamer surface is
      obtained from a relatively small amount of electrostatic neutralization of the
      DNA phosphate charge by positively charged histone groups, especially arginine
      residues. Here we present a theoretical analysis of a simple model that
      emphasizes the competition between the high degree of bending of the stiff DNA
      molecule required for its tight curvature on the histone octamer and the
      neutralization of the DNA phosphate charge by basic histone residues. Our
      calculation accounts for the strong influence of condensed counterions on the
      electrostatic interactions. We find that the minimum amount of free energy
      required to bend DNA into axial conformity with the superhelical ramp at
      physiological salt concentration can be provided by a scant 6% neutralization of
      the phosphate charge, in close correspondence to the stoichiometric
      neutralization of phosphate charge by the arginine side chain that intrudes into
      the inward-facing minor groove of each DNA double helical turn.

PMID- 14653744
TI  - Hydrogen bonding interfaces in fullerene*TTF ensembles.
AB  - Novel thermodynamically stable supramolecular donor-acceptor dyads have been
      synthesized. In particular, we assembled successfully C(60), as an electron
      acceptor, with the strong electron donor TTF through a complementary guanidinium
      carboxylate ion pair. Two strong and well-oriented hydrogen bonds, in combination
      with ionic interactions, ensure the formation of stable donor-acceptor dyads. The
      molecular architecture has been fine-tuned by using chemical spacers of different
      lengths (i.e., phenyl versus biphenyl) and functional groups (i.e., ester versus
      amide), thus providing meaningful incentives to differentiate between through
      bond and through-space electron-transfer scenarios. In electrochemical studies,
      both the donor and acceptor character of the TTF and C(60) units, respectively,
      have been clearly identified. Steady-state and time-resolved emission studies,
      however, show a solvent-dependent fluorescence quenching in C(60)*TTF dyads as
      well as the formation of the C(60)(*)(-)*TTF(*)(+) radical ion pairs, for which
      we determined lifetimes that are in the range of hundred of nanoseconds to
      microseconds. The complex network that connects C(60) with TTF in the dyads and
      the flexible nature of the spacer result in through-space electron-transfer
      processes. This first example of electron transfer in C(60)-based dyads,
      connected by strong hydrogen bonds, demonstrates that this approach can add
      outstanding benefits to the construction of artificial photosynthetic systems
      that bear a closer resemblance to the natural one.

PMID- 14653745
TI  - Water-compatible molecularly imprinted polymers obtained via high-throughput
      synthesis and experimental design.
AB  - A technique allowing high-throughput synthesis and evaluation of molecularly
      imprinted polymer sorbents at a reduced scale (mini-MIPs) was developed and used
      for the optimization of MIPs for use in pure aqueous environments. The technique
      incorporated a 4-port liquid-handling robot for the rapid dispensing of monomers,
      templates, solvents and initiator into the reaction vessels of a 96-well plate. A
      library of 80 polymers, each ca. 50 mg, could thus be prepared in 24 h. The MIP
      rebinding capacity and selectivity could be rapidly assessed in the batch mode by
      quantifying nonbound fractions in parallel using a UV monochromator plate reader.
      This allowed a complete evaluation of the binding characteristics of an 80
      polymer library in approximately 1 week. With the objective of optimizing a
      polymer imprinted with the local anaesthetic Bupivacaine for use in pure aqueous
      systems, a polymer library was prepared by varying the original poly(MAA-co-EDMA)
      MIP composition. The variable factors were the added amount of the hydrophilic
      comonomer, 2-hydroxyethyl methacrylate (HEMA), the cross-linking ratio, and the
      porogen. This optimization resulted in polymers showing high imprinting factors
      (IF = K(MIP)/K(NIP)) in water as a result, mainly, of reduced binding to the
      nonimprinted polymer. Normal scale batches of these materials showed strong
      retention of the template and low nonspecific binding when assessed as
      chromatographic stationary phases using pure phosphate buffer, pH 7.4, as mobile
      phase, by equilibrium batch rebinding experiments and as sorbents for extractions
      of the analyte from blood plasma samples.

PMID- 14653746
TI  - Heats of formation of [2.2]paracyclophane-1-ene and [2.2]paracyclophane-1,9-diene
      - an experimental study.
AB  - The enthalpies of formation [Delta(g)] of tricyclo[8.2.2.2(4,7)]hexadeca
      1(13),2,4(16),5,7(15),10(14),11-heptaene (2, 1,2-dehydro[2.2]paracyclophane or
      [2.2]paracyclophane-1-ene) and tricyclo[8.2.2.2(4,7)]hexadeca
      1(13),2,4(16),5,7(15),8,10(14),11-octaene (3, 1,2,9,10-dehydro[2.2]paracyclophane
      or [2.2]paracyclophane-1,9-diene) have been determined by measuring their heats
      of combustion in a microcalorimeter and their heats of sublimation by the
      transpiration method. Values of the strain energies (SE) [SE(2) = 34.7 kcal mol(
      )(1), SE(3) = 42.0 kcal mol(-)(1)] have been derived from the gas-phase heats of
      formation and are compared with those from MM3 and PM3 calculations and with the
      corresponding value SE(1) = 30.1 kcal mol(-)(1) for the parent
      tricyclo[8.2.2.2(4,7)]hexadeca-1(13),4(16),5,7(15),10(14),11-hexaene (1,
      [2.2]paracyclophane). The higher strain energies of 2 and 3 (by 4.6 and 11.9 kcal
      mol(-)(1)) are in accord with the well-known increased reactivities of their
      aromatic rings as a consequence of their increased bending. As revealed by an X
      ray crystal structure analysis, the bending in the monoene 2 corresponds to that
      of 1 and 3 at one of two bridging corners.

PMID- 14653747
TI  - Lithium diisopropylamide-mediated lithiations of imines: insights into highly
      structure-dependent rates and selectivities.
AB  - Lithium diisopropylamide-mediated lithiations of N-alkyl ketimines derived from
      cyclohexanones reveal that simple substitutions on the N-alkyl side chain and the
      2-position of the cyclohexyl moiety afford a 60,000-fold range of rates. Detailed
      rate studies implicate monosolvated monomers at the rate-limiting transition
      structures in all instances. Comparisons of experimentally derived
      regioselectivities and rates, taken in conjunction with density functional theory
      computational studies, reveal a number of factors that influence reactivities
      including: (a) axial versus equatorial disposition of the proton on the
      cyclohexane ring, (b) syn versus anti orientation of the lithiation relative to
      the N-alkyl group, (c) the presence or absence of a potentially chelating methoxy
      moiety on the N-alkyl group, (d) the presence of a 2-methyl substituent at the
      geminal or distal alpha-carbon, and (e) branching in the N-alkyl group. The
      isolated contributions are not large, yet they display a strong and predictable
      additivity leading to a kinetic resolution of imines derived from racemic 2
      methylcyclohexanone.

PMID- 14653748
TI  - Hydrazide-based quadruply hydrogen-bonded heterodimers. Structure, assembling
      selectivity, and supramolecular substitution.
AB  - This paper describes the synthesis, self-assembly, and characterization of a new
      class of highly stable hydrazide-based quadruply hydrogen-bonded heterodimers.
      All of the hydrazide-derived heterodimers possess the complementary ADDA-DAAD
      hydrogen-bonding sequences. Hydrazide derivatives 1, which has two intramolecular
      S(6) RO.H-N hydrogen bonds, and 2 complex to afford two fastly exchanging
      isomeric heterodimers 1.2 and 1.2' in chloroform, as a result of two different
      conformational arrangements of 2. An average binding constant K(assoc) of 4.7 x
      10(4) M(-)(1) was determined for heterodimer 1.2 and 1.2' by (1)H NMR titration
      of 1 with changing 2 in chloroform-d. In contrast, 1 binds 11 and 12, both of
      which are introduced with two intramolecular S(6) hydrogen bonds, to exclusively
      afford heterodimers 1.11 and 1.12, with K(assoc) values of 1.8 x 10(4) and 5.0 x
      10(2) M(-)(1), respectively. Fluorine-containing 19, which has a hydrazide
      skeleton identical to that of 1 but two intramolecular S(6) F.H-N hydrogen bonds,
      can also complex with 2, 11, and 12, to afford heterodimers 19.2, 19.2', 19.11,
      and 19.12, with K(assoc) values of of 1.2 x 10(4) (average value for 19.2 and
      19.2'), 5.4 x 10(3), and 1.9 x 10(2) M(-)(1), respectively. The structures of the
      new heterodimers have been proven with NOESY, IR, and VPO (for some of the
      heterodimers) experiments. Moreover, 1 and 19 can also strongly bind 2,7
      dilauroylamido-1,8-naphthyridine 23 to afford dimers 1.23 and 19.23 with K(assoc)
      values of 6.0 x 10(5) and 1.4 x 10(5) M(-)(1), respectively. Adding 1 to the 1:1
      solution of 23 and 1-octyl-3-(4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl)urea
      24 or 1-octyl-3-(4-oxo-1,4-dihydro-pyrimidin-2-yl)urea 25, which had been
      developed initially by Zimmerman and Meijer, respectively, induces dimers 23.24
      and 23.25 to dissociate, leading to the formation of dimers 1.23 and 24.24 or
      25.25, respectively. The new hydrazide-based hydrogen-bonding modules described
      are useful building blocks for self-assembly and open a new avenue to recognition
      between discrete supramolecular species.

PMID- 14653749
TI  - Water-mediated association provides an ion pair receptor.
AB  - In this paper, we report on the formation and properties of a water-stabilized
      dimer comprising calix[4]arene-guanosine conjugate cG 2. The 1,3-alternate
      calixarene cG 2 was poorly soluble in dry CDCl(3) and gave an ill-resolved NMR
      spectrum, consistent with its nonspecific aggregation. The compound was much more
      soluble in water-saturated CDCl(3). Two sets of well-resolved (1)H NMR signals
      for the guanosine residues in cG 2, present in a 1:1 ratio, indicated that the
      compound's D(2) symmetry had been broken and provided the first hint that cG 2
      dimerizes in water-saturated CDCl(3). The resulting dimer, (cG
      2)(2).(H(2)O)(n)(), has a unique property: it extracts alkali halide salts from
      water into organic solution. This dimer is a rare example of a self-assembled ion
      pair receptor. The identity of the (cG 2)(2).NaCl.(H(2)O)(n)() dimer was
      confirmed by comparing its self-diffusion coefficient in CDCl(3), determined by
      pulsed-field gradient NMR, with that of control compound cA 3, an adenosine
      analogue. The dimer's stoichiometry was also confirmed by quantitative
      measurement of the cation and anion using ion chromatrography. Two-dimensional
      NMR and ion-induced NMR shifts indicated that the cation binding site is formed
      by an intermolecular G-quartet and the anion binding site is provided by the 5'
      amide NH groups. Once bound, the salt increases the dimer's thermal stability.
      Both (1)H NMR and ion chromatography measurements indicated that the cG 2 dimer
      has a modest selectivity for extracting K(+) over Na(+) and Br(-) over Cl(-). The
      anion's identity also influences the association process: NaCl gives a soluble,
      discrete dimer whereas addition of NaBPh(4) to (cG 2)(2).(H(2)O)(n)() leads to
      extensive aggregation and precipitation. This study suggests a new direction for
      ion pair receptors, namely, the use of molecular self-assembly. The study also
      highlights water's ability to stabilize a functional noncovalent assembly.

PMID- 14653750
TI  - Solid-state synthesis of a conducting polythiophene via an unprecedented
      heterocyclic coupling reaction.
AB  - Prolonged storage ( approximately 2 years) or gentle heating (50-80 degrees C) of
      crystalline 2,5-dibromo-3,4-ethylenedioxythiophene (DBEDOT) affords a highly
      conducting, bromine-doped poly(3,4-ethylenedioxythiophene) (PEDOT), as confirmed
      by solid-state NMR, FTIR, CV, and vis-NIR spectroscopies. The novel solid-state
      polymerization (SSP) does not occur for 2,5-dichloro-3,4-ethylenedioxythiophene
      (DCEDOT), and requires a much higher temperature (>130 degrees C) for 2,5-diiodo
      3,4-ethylenedioxythiophene (DIEDOT). X-ray structural analysis of the above
      dihalothiophenes reveals short Hal.Hal distances between adjacent molecules in
      DBEDOT and DIEDOT, but not in DCEDOT. The polymerization may also occur in the
      melt but is significantly slower and leads to poorly conductive material.
      Detailed studies of the reaction were performed using ESR, DSC, microscopy, and
      gravimetric analyses. SSP starts on crystal defect sites; it is exothermic by 14
      kcal/mol and requires activation energy of approximately 26 kcal/mol (for
      DBEDOT). The temperature dependence of the conductivity of SSP-PEDOT (sigma(rt) =
      20-80 S/cm) reveals a slight thermal activation. It can be further increased by a
      factor of 2 by doping with iodine. Using this approach, thin films of PEDOT with
      conductivity as high as 20 S/cm were fabricated on insulating flexible plastic
      surfaces.

PMID- 14653751
TI  - Why are silyl ethers conformationally different from alkyl ethers? Chair-chair
      conformational equilibria in silyloxycyclohexanes and their dependence on the
      substituents on silicon. The wider roles of eclipsing, of 1,3-repulsive steric
      interactions, and of attractive steric interactions.
AB  - An NMR study of the diaxial/diequatorial chair equilibrium in a range of
      silylated derivatives of trans-1,4- and trans-1,2-dihydroxycyclohexane is
      reported and discussed with a view to explaining unusually large populations of
      chair conformations with axial substituents, noted previously for some
      monosilyloxycyclohexanes and in some silylated sugars. X-ray diffraction studies
      of three bis-triphenylsilyloxycyclohexanes are reported and show both axial and
      equatorial silyloxy groups with the exocyclic bonds eclipsed. Eclipsing is also
      suggested by molecular mechanics (MM3) calculations on such derivatives. Both
      axial and equatorial tertiary silyl groups have 1,3-repulsive interactions with
      whatever substituents or hydrogen atoms are at the two adjacent equatorial
      positions, and these are relieved by rotation toward the eclipsed conformation of
      the exocyclic C-O bond. The three substituents on silicon interact attractively
      with the nine atoms at the 3, 4, and 5-positions of the cyclohexane ring and
      calculations suggest that these stabilizing interactions are significantly
      greater in the axial than in the equatorial conformation. An equatorial C-OSiR(3)
      bond with one or two equatorial neighbors has a restricted potential energy well
      that becomes much broader when the bond is axial without any equatorial neighbors
      in the alternative chair. Adjacent silyl groups in the 1,2-disubstituted series
      interact in a stabilizing way overall in all conformations, this being
      particularly marked in the diaxial conformation of the more complex ethers. These
      factors lead to unusually large axial populations.

PMID- 14653752
TI  - Sidewall carboxylic acid functionalization of single-walled carbon nanotubes.
AB  - The reactions of single-walled carbon nanotubes (SWNTs) with succinic or glutaric
      acid acyl peroxides in o-dichlorobenzene at 80-90 degrees C resulted in the
      addition of 2-carboxyethyl or 3-carboxypropyl groups, respectively, to the
      sidewalls of the SWNT. These acid-functionalized SWNTs were converted to acid
      chlorides by derivatization with SOCl(2) and then to amides with terminal
      diamines such as ethylenediamine, 4,4'-methylenebis(cyclohexylamine), and
      diethyltoluenediamine. The acid-functionalized SWNTs and the amide derivatives
      were characterized by a set of materials characterization methods including
      attenuated total reflectance (ATR) FTIR, Raman and solid state (13)C NMR
      spectroscopy, transmission electron microscopy (TEM), and thermal gravimetry-mass
      spectrometry (TG-MS). The degree of SWNT sidewall functionalization with the acid
      terminated groups was estimated as 1 in 24 carbons on the basis of TG-MS data. In
      comparison with the pristine SWNTs, the acid-functionalized SWNTs show an
      improved solubility in polar solvents, for example, alcohols and water, which
      enables their processing for incorporation into polymer composite structures as
      well as for a variety of biomedical applications.

PMID- 14653753
TI  - Phase transformation driven by valence electron concentration: tuning interslab
      bond distances in Gd5GaxGe4-x.
AB  - X-ray single crystal and powder diffraction studies on the Gd(5)Ga(x)()Ge(4)(
      )(x)() system with 0 < or = x < or = 2.2 reveal dependence of interslab T-T dimer
      distances and crystal structures themselves on valence electron concentration (T
      is a mixture of Ga and Ge atoms). While the Gd(5)Ga(x)()Ge(4)(-)(x)() phases with
      0 < or = x < or = 0.6 and valence electron concentration of 30.4-31 e(-)/formula
      crystallize with the Sm(5)Ge(4)-type structure, in which all interslab T-T dimers
      are broken (distances exceeding 3.4 A), the phases with 1 < or = x < or = 2.2 and
      valence electron concentration of 28.8-30 e-/formula adopt the Pu(5)Rh(4)- or
      Gd(5)Si(4)-type structures with T-T dimers between the slabs. An orthorhombic
      Pu(5)Rh(4)-type structure, which is intermediate between the Gd(5)Si(4)- and
      Sm(5)Ge(4)-type structures, has been identified for the Gd(5)GaGe(3) composition.
      Tight-binding linear-muffin-tin-orbital calculations show that substitution of
      three-valent Ga by four-valent Ge leads to larger population of the antibonding
      states within the dimers and, thus, to dimer stretching and eventually to dimer
      cleavage.

PMID- 14653754
TI  - An evaluation of amide group planarity in 7-azabicyclo[2.2.1]heptane amides. Low
      amide bond rotation barrier in solution.
AB  - Here we show that amides of bicyclic 7-azabicyclo[2.2.1]heptane are intrinsically
      nitrogen-pyramidal. Single-crystal X-ray diffraction structures of some relevant
      bicyclic amides, including the prototype N-benzoyl-7-azabicyclo[2.2.1]heptane,
      exhibited nitrogen-pyramidalization in the solid state. We evaluated the
      rotational barriers about the amide bonds of various N-benzoyl-7
      azabicyclo[2.2.1]heptanes in solution. The observed reduction of the rotational
      barriers of the bicyclic amides, as compared with those of the monocyclic
      pyrrolidine amides, is consistent with a nitrogen-pyramidal structure of 7
      azabicyclo[2.2.1]heptane amides in solution. A good correlation was found between
      the magnitudes of the rotational barrier of N-benzoyl-7-azabicyclo[2.2.1]heptanes
      bearing para-substituents on the benzoyl group and the Hammett's sigma(p)(+)
      constants, and this is consistent with the similarity of the solution structures.
      Calculations with the density functional theory reproduced the nitrogen-pyramidal
      structures of these bicyclic amides as energy minima. The calculated magnitudes
      of electron delocalization from the nitrogen nonbonding n(N) orbital to the
      carbonyl pi orbital of the amide group evaluated by application of the bond model
      theory correlated well with the rotational barriers of a variety of amides,
      including amides of 7-azabicyclo[2.2.1]heptane. The nonplanarity of the amide
      nitrogen of 7-azabicyclo[2.2.1]heptanes would be derived from nitrogen
      pyramidalization due to the CNC angle strain and twisting of the amide bond due
      to the allylic strain.

PMID- 14653755
TI  - Theoretical study of samarium (II) carbenoid (ISmCH2I) promoted cyclopropanation
      reactions with ethylene and the effect of THF solvent on the reaction pathways.
AB  - A computational study of the cyclopropanation reactions of divalent samarium
      carbenoid ISmCH(2)I with ethylene is presented. The reaction proceeds through two
      competing pathways: methylene transfer and carbometalation. The ISmCH(2)I species
      was found to have a "samarium carbene complex" character with properties similar
      to previously investigated lithium carbenoids (LiCH(2)X where X = Cl, Br, I). The
      ISmCH(2)I carbenoid was found to be noticeably different in structure with more
      electrophilic character and higher chemical reactivity than the closely related
      classical Simmons-Smith (IZnCH(2)I) carbenoid. The effect of THF solvent was
      investigated by explicit coordination of the solvent THF molecules to the Sm (II)
      center in the carbenoid. The ISmCH(2)I/(THF)(n)() (where n = 0, 1, 2) carbenoid
      methylene transfer pathway barriers to reaction become systematically lower as
      more THF solvent is added (from 12.9 to 14.5 kcal/mol for no THF molecules to 8.8
      to 10.7 kcal/mol for two THF molecules). In contrast, the reaction barriers for
      cyclopropanation via the carbometalation pathway remain high (>15 kcal/mol). The
      computational results are briefly compared to other carbenoid reactions and
      related species.

PMID- 14653756
TI  - Thermal activation of hydrocarbon C-H bonds initiated by a tungsten allyl
      complex.
AB  - Gentle thermolysis of the allyl complex, CpW(NO)(CH(2)CMe(3))(eta(3)
      H(2)CCHCMe(2)) (1), at 50 degrees C in neat hydrocarbon solutions results in the
      loss of neopentane and the generation of transient intermediates that
      subsequently activate solvent C-H bonds. Thus, thermal reactions of 1 with
      tetramethylsilane, mesitylene, and benzene effect single C-H activations and lead
      to the exclusive formation of CpW(NO)(CH(2)SiMe(3))(eta(3)-H(2)CCHCMe(2)) (2),
      CpW(NO)(CH(2)C(6)H(3)-3,5-Me(2))(eta(3)-H(2)CCHCMe(2)) (3), and
      CpW(NO)(C(6)H(5))(eta(3)-H(2)CCHCMe(2)) (4), respectively. The products of
      reactions of 1 with other methyl-substituted arenes indicate an inherent
      preference of the system for the activation of stronger arene sp(2) C-H bonds.
      For example, C-H bond activation of p-xylene leads to the formation of
      CpW(NO)(CH(2)C(6)H(4)-4-Me)(eta(3)-H(2)CCHCMe(2)) (5) (26%) and CpW(NO)(C(6)H(3)
      2,5-Me(2))(eta(3)-H(2)CCHCMe(2)) (6) (74%). Mechanistic and labeling studies
      indicate that the transient C-H-activating intermediates are the allene complex,
      CpW(NO)(eta(2)-H(2)C=C=CMe(2)) (A), and the eta(2)-diene complex, CpW(NO)(eta(2)
      H(2)C=CHC(Me)=CH(2)) (B). Intermediates A and B react with cyclohexene to form
      CpW(NO)(eta(3)-CH(2)C(2-cyclohexenyl)CMe(2))(H) (18) and CpW(NO)(eta(3)
      CH(2)CHC)(Me)CH(2)C(beta)H(C(4)H(8))C(alpha)H (19), respectively, and
      intermediate A can be isolated as its PMe(3) adduct, CpW(NO)(PMe(3))(eta(2)
      H(2)C=C=CMe(2)) (20). Interestingly, thermal reaction of 1 with 2,3-dimethylbut-2
      ene results in the formation of a species that undergoes eta(3) --> eta(1)
      isomerization of the dimethylallyl ligand following the initial C-H bond
      activating step to yield CpW(NO)(eta(3)-CMe(2)CMeCH(2))(eta(1)-CH(2)CHCMe(2))
      (21). Thermolyses of 1 in alkane solvents afford allyl hydride complexes
      resulting from three successive C-H bond-activation reactions. For instance, 1 in
      cyclohexane converts to CpW(NO)(eta(3)-C(6)H(9))(H) (22) with
      dimethylpropylcyclohexane being formed as a byproduct, and in methylcyclohexane
      it forms the two isomeric complexes, CpW(NO)(eta(3)-C(7)H(11))(H) (23a,b). All
      new complexes have been characterized by conventional spectroscopic methods, and
      the solid-state molecular structures of 2, 3, 4, 18, 19, 20, and 21 have been
      established by X-ray crystallographic analyses.

PMID- 14653757
TI  - Theoretical investigation of the "CO in"-"CO out" isomerization in a [2Fe-2S]
      ferredoxin: free energy profiles and redox states.
AB  - This paper reports on extensive molecular dynamics simulations (about 40 ns in
      total) in both the reduced and the oxidized states of Ferredoxin from
      Cyanobacterium Anabaena PCC7119. These calculations have provided us with the
      free energy profile of the phi(47) backbone angle which controls the "CO in" to
      "CO out" transition of Cys46 in the reduced and oxidized Fd7119. Our main
      motivation has been to identify the time scales involved in the reduction of Fd
      and single out the amino acid residues crucially affecting the conformational
      change and, thus, electron transfer. The free energy profiles obtained in this
      study are relevant to electron transfers in the PSI/Fd7119 and Fd7119/FNR
      complexes. Our findings based on hydrated ferredoxin simulations are that
      activated processes are to occur in the protein during electron transfer to and
      from ferredoxin. The relative stability and the activation barrier of the "CO in"
      to "CO out" transition can be modulated by the distance between the Ser47 and the
      Glu94 residues. In our calculations, for short distances, the "CO in" state is
      favored in the reduced form, whereas for large distances, the "CO out" state
      becomes increasingly favored. Accordingly, conformational changes in Fd7119 when
      bound to PSI or FNR can have crucial effects on the kinetics of the electron
      transfer. Our simulations also show that the hydrogen bond between between
      Ser47(OG) and Cys46(O) is essential to lock in the "CO out" state. This finding
      explains why only the Ser47Thr Fd7119 mutant sustains electron transfer activity,
      as only residues serine and threonine can form a specific hydrogen bond with
      Cys46(O). Finally, our simulations predict that Phe65 has a large probability of
      being in close contact with the Cys46(O) at the top of the conformational free
      energy barrier. This carbonyl/phenyl ring interaction can then facilitate the de
      localization of the Fd's electron toward the Pi orbitals of Phe65 aromatic ring
      which is thought to be crucial to the Fd7119/FNR electron transfer

PMID- 14653758
TI  - Molecular dynamics simulation of the formation, structure, and dynamics of small
      phospholipid vesicles.
AB  - Here, we use coarse grained molecular dynamics (MD) simulations to study the
      spontaneous aggregation of dipalmitoylphosphatidylcholine (DPPC) lipids into
      small unilamellar vesicles. We show that the aggregation process occurs on a
      nanosecond time scale, with bicelles and cuplike vesicles formed at intermediate
      stages. Formation of hemifused vesicles is also observed at higher lipid
      concentration. With either 25% dipalmitoylphosphatidylethanolamine (DPPE) or
      lysoPC mixed into the system, the final stages of the aggregation process occur
      significantly faster. The structure of the spontaneously formed vesicles is
      analyzed in detail. Microsecond simulations of isolated vesicles reveal
      significant differences in the packing of the lipids between the inner and outer
      monolayers, and between PC, PE, and lysoPC. Due to the small size of the vesicles
      they remain almost perfectly spherical, undergoing very limited shape
      fluctuations or bilayer undulations. The lipid lateral diffusion rate is found to
      be faster in the outer than in the inner monolayer. The water permeability
      coefficient of the pure DPPC vesicles is of the order of 10(-)(3) cm s(-)(1), in
      agreement with experimental measurements.

PMID- 14653759
TI  - Optically activated functionalization reactions in Si quantum dots.
AB  - Using ab initio calculations, we have studied the influence of optical activation
      on functionalization reactions of silicon quantum dots with unsaturated
      hydrocarbons. We find that the energy barrier for the replacement of silicon
      hydrogen with silicon-carbon bonds is dramatically reduced if the silicon dot is
      optically excited. These results provide an explanation for recent experiments on
      optically excited porous silicon. In addition, our calculations point at the
      existence of an intermediate spin-polarized state formed by the dot and an alkene
      or alkyne, upon relaxation after absorbing a photon. This state could be detected
      experimentally, by, for example, electron spin resonance measurements. Based on
      the results of our calculations as a function of the dot size, varied from 0.8 to
      1.5 nm, we propose that light activated reactions could be used to functionalize
      and size select silicon quantum dots at the same time.

PMID- 14653760
TI  - Molecular quantum cellular automata cells. Electric field driven switching of a
      silicon surface bound array of vertically oriented two-dot molecular quantum
      cellular automata.
AB  - The amine functionality of the linker on the dinuclear complex [trans
      Ru(dppm)(2)(Ctbd1;CFc)(NCCH(2)CH(2)NH(2))][PF(6)] reacts with Si-Cl bonds of a
      chlorinated, highly B doped Si (111) surface to yield Si-N surface-complex bonds.
      The surface bound complex is constrained to a near vertical orientation by the
      chain length of the linker as confirmed by variable angle XPS. Oxidation of the
      dinuclear complex with ferrocenium ion or electrochemically generates a stable,
      biased Fe(III)-Ru(II) mixed-valence complex on the surface. Characterization of
      the array of surface bound complexes with spectroscopic as well as
      electrochemical techniques confirms the presence of strongly bound, chemically
      robust, mixed-valence complexes. Capping the flat array of complexes with a
      minimally perturbing mercury electrode permits the equalization of the Fe and Ru
      energy wells by an applied electric field. The differential capacitance of
      oxidized and unoxidized bound complexes is compared as a function of voltage
      applied between the Hg gate and the Si. The results show that electron exchange
      between the Fe and Ru sites of the array of dinuclear mixed-valence complexes at
      energy equalization generates a fluctuating dipole that produces a maximum in the
      capacitance versus voltage curve for each complex-counterion combination present.
      Passage through the capacitance maximum corresponds to switching of the molecular
      quantum cellular automata (QCA) cell array by the electric field from the Fe(III)
      Ru(II) configuration to the Fe(II)-Ru(III) configuration, thereby confirming that
      molecules possess an essential property necessary for their use as elements of a
      QCA device.

PMID- 14653761
TI  - Evidence for an initiation of the methanol-to-olefin process by reactive surface
      methoxy groups on acidic zeolite catalysts.
AB  - Recent progress reveals that, in the methanol-to-olefin (MTO) process on acidic
      zeolites, the conversion of an equilibrium mixture of methanol and DME is
      dominated by a "hydrocarbon pool" mechanism. However, the initial C-C bond
      formation, that is, the chemistry during the kinetic "induction period" leading
      to the reactive hydrocarbon pool, still remains unclear. With the application of
      a stopped-flow protocol, in the present work, pure surface methoxy groups
      [SiO(CH(3))Al] were prepared on various acidic zeolite catalysts (H-Y, H-ZSM-5, H
      SAPO-34) at temperatures lower than 473 K, and the further reaction of these
      methoxy species was investigated by in situ (13)C MAS NMR spectroscopy. By using
      toluene and cyclohexane as probe molecules which are possibly involved in the MTO
      process, we show the high reactivity of surface methoxy species. Most
      importantly, the formation of hydrocarbons from pure methoxy species alone is
      demonstrated for the first time. It was found that (i) surface methoxy species
      react at room temperature with water to methanol, indicating the occurrence of a
      chemical equilibrium between these species at low temperatures. In the presence
      of aromatics and alkanes, (ii) the reactivity of surface methoxy groups allows a
      methylation of these organic compounds at reaction temperatures of ca. 433 and
      493 K, respectively. In the absence of water and other organic species, that is,
      under flow conditions and on partially methylated catalysts, (iii) a conversion
      of pure methoxy groups alone to hydrocarbons was observed at temperatures of T
      >/= 523 K. This finding indicates a possible formation of the first hydrocarbons
      during the kinetic induction period of the MTO process via the conversion of pure
      surface methoxy species (case iii). After the first hydrocarbons are formed, or
      in the presence of a small amount of organic impurities, surface methoxy groups
      contribute to a further methylation of these organic compounds (case ii), leading
      to the formation of a reactive hydrocarbon pool which eventually plays an active
      role in the steady state of the MTO process at reaction temperatures of T >/= 573
      K.

PMID- 14653764
TI  - "Fish on Steroids"?

PMID- 14653765
TI  - Nutritional support for wound healing.
AB  - Healing of wounds, whether from accidental injury or surgical intervention,
      involves the activity of an intricate network of blood cells, tissue types,
      cytokines, and growth factors. This results in increased cellular activity, which
      causes an intensified metabolic demand for nutrients. Nutritional deficiencies
      can impede wound healing, and several nutritional factors required for wound
      repair may improve healing time and wound outcome. Vitamin A is required for
      epithelial and bone formation, cellular differentiation, and immune function.
      Vitamin C is necessary for collagen formation, proper immune function, and as a
      tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin;
      however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain
      reduces edema, bruising, pain, and healing time following trauma and surgical
      procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic
      acid production in the wound. Adequate dietary protein is absolutely essential
      for proper wound healing, and tissue levels of the amino acids arginine and
      glutamine may influence wound repair and immune function. The botanical medicines
      Centella asiatica and Aloe vera have been used for decades, both topically and
      internally, to enhance wound repair, and scientific studies are now beginning to
      validate efficacy and explore mechanisms of action for these botanicals. To
      promote wound healing in the shortest time possible, with minimal pain,
      discomfort, and scarring to the patient, it is important to explore nutritional
      and botanical influences on wound outcome.

PMID- 14653766
TI  - Bovine colostrums: a review of clinical uses.
AB  - Bovine colostrums are the "early" milk produced by cows during the first several
      days post-parturition. This "early" milk has a nutrient profile and immunological
      composition that differs substantially from "mature" milk. Included in the
      nutrient profile are higher amounts of immunoglobulins, growth factors,
      cytokines, and nucleosides than are found in milk. Bovine colostrums are also
      rich in oligosaccharides, antimicrobials, and immune-regulating factors.
      Available evidence suggests a beneficial effect of supplementation of bovine
      colostrums in improving body composition, aspects of athletic performance,
      diarrhea in persons with immune-deficiency syndromes, NSAID-induced
      gastrointestinal disturbances, and aspects of the acute phase response that
      occurs secondary to surgery. Specific hyperimmune bovine colostrums, produced to
      have high neutralizing titer activity against Cryptosporidia, H. pylori, measles,
      rotavirus, and Shigella sp., appear to have clinical utility in conditions
      associated with these infectious organisms.

PMID- 14653767
TI  - Portal to the interior: viral pathogenesis and natural compounds that restore
      mucosal immunity and modulate inflammation.
AB  - Most antigens, particularly viruses, enter the body through the mucosal epithelia
      where they are carried by afferent lymphatics to regional lymph nodes for
      presentation to the immune system. Although they share immunological
      similarities, immune processes that protect the mucosa are distinct from innate
      and acquired immunity. The barrier formed by the intestinal mucosa is the most
      studied, with its microenvironment having a marked influence on both local and
      systemic immune responses. A healthy microenvironment and resilient neighboring
      tissue provide protection against inflammation known to dampen mucosal immunity,
      promote carcinogenesis, contribute to systemic inflammatory processes, and result
      in autoimmune diseases. Numerous natural substances improve this microenvironment
      and thereby enhance immunity against microbial infections. Since mucosal immunity
      forms the first line of defense against many commonly transmitted pathogens,
      restoring and maintaining mucosal immunity is critical for disease prevention and
      intervention. This article discusses the nature of mucosal immunity and its
      relationship to viral infections and other conditions, and reviews natural
      compounds that help restore mucosal immunity.

PMID- 14653768
TI  - Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and
      therapeutic value in major depression.
AB  - Omega-3 fatty acids have been the subject of volumes of international research,
      the results of which indicate these substances may have therapeutic value in a
      number of medical conditions. An emerging area of research is examining the
      neurobehavioral aspects of omega-3 fatty acids (alpha-linolenic,
      eicosapentaenoic, docosahexaenoic) and the critical role of these essential fats
      in the functioning of the central nervous system. Investigations have linked
      omega-3 fatty acids to a number of neuropsychiatric disorders, including
      depression. The purpose of this article is to examine the possible mechanisms of
      action and potential clinical value of omega-3 fatty acids in major depression. A
      novel mechanism involving omega-3 modulation of cAMP response element binding
      protein (CREB) and brain-derived neurotrophic factor (BDNF) is proposed.

PMID- 14653769
TI  - Interstitial cystitis: understanding the syndrome.
AB  - Interstitial cystitis (IC) is a chronic pain syndrome that affects close to a
      million people in the United States. The syndrome presents differently in many
      individuals, with the unifying factor being chronic pelvic pain and disruption of
      daily life activities. Many etiologies have been proposed as causative factors
      for IC, although it is likely triggered by more than one process. Treatment for
      many individuals revolves around symptom management and improving quality of
      life; however, it is imperative to remove aggravating factors such as food and
      daily stressors. Treatment will vary for individuals, as symptoms and etiology
      will differ. This article discusses nutritional and other non-toxic approaches to
      treating IC.

PMID- 14653770
TI  - Methylsulfonylmethane (MSM). Monograph.

PMID- 14653771
TI  - Oligomeric proanthocyanidins (OPCs). Monograph.

PMID- 14653772
TI  - Socialized medicine hooray? Part 2. War surgeon; Rx of superior oblique paresis;
      High AC/A illusion? Stereopsis with no macula; Vision screening: a review: and a
      breakout!

PMID- 14653773
TI  - Unilateral superior oblique paresis: deviation patterns and surgical indications.
AB  - PURPOSE: To analyze different patterns of vertical strabismic deviations seen in
      unilateral superior oblique (SO) paresis, and the response to surgical treatment,
      in order to discern the most effective surgical indication to treat each clinical
      pattern. MATERIAL AND METHOD: A retrospective analysis of 110 patients with a
      diagnosis of unilateral SO paresis studied according to the follow protocol: a)
      Hypertropia (HT) measurement with alternate prism and cover test in the 9
      diagnostic gaze positions; b) Determination of the deviation pattern; and c)
      Analysis of the results achieved with various surgical procedures. RESULTS: We
      found that unilateral SO paresis presented with 3 patterns of HT: 1) Patients
      with marked incomitance between opposite lateroversions; 2) Cases with HT equal
      to or greater than 20 prism diopters in primary gaze position, lower incomitance
      between opposite lateroversions and incomitance in up- and downgaze; and 3) A
      pattern of vertical deviation characterized by a strong tendency to comitance in
      the 9 diagnostic gaze positions, with an overtly positive Bielschowsky Head Tilt
      Test and extorsion of the affected eye. CONCLUSIONS: This study provides
      guidelines to discern the most effective surgical indication for patients with
      unilateral SO paresis on the basis of the presenting hypertropia pattern.

PMID- 14653774
TI  - Intermittent exotropia with high AC/A ratio: is it a bane to surgical cure? Some
      facts and fictions of the two clinical tests: occlusion of one eye and the use of
      +3.00 spherical lenses.
AB  - BACKGROUND AND PURPOSE: To review the multiple factors in intermittent exotropia
      (X(T)) responsible for the discrepancy between the distance and near deviations;
      to challenge the classification of X(T) into types according to the two standard
      clinical tests of occlusion of one eye and the use of +3.00 D spherical lenses at
      near by demonstrating the pitfalls of these two tests, as in X(T), masquerading
      as high AC/A ratio at times or as strong proximal fusional convergence at other
      times. METHODS OF STUDY: Fifteen patients demonstrating findings characteristic
      of X(T) with so-called high AC/A ratio are reported. Fourteen patients had an
      exodeviation initially. The fifteenth had become exotropic following medial
      rectus recessions for infantile esotropia. Fourteen patients had bilateral
      lateral rectus recession and one had unilateral lateral rectus recession.
      RESULTS: The only patient who did develop a long term postoperative overcorrected
      high AC/A ratio esotropia was the patient who had initially an infantile
      esotropia. Of the other 14 patients initially X(T) none developed a long term
      postoperative overcorrected high AC/A ratio esotropia. Fifty % of these were
      "cured" (OT +/- 8 delta) and 50% had a "significant (> or = 8 delta) recurrence"
      of their exodeviation. CONCLUSION: Patients with intermittent exotropia and
      significantly more exodeviation at distance than at near, and classified to have
      high AC/A ratio by occlusion of one eye and the use of +3.00 spheres at near, do
      not necessarily have a high accommodation-convergence relationship but rather,
      other factors mimicking this high AC/A relationship. They do not necessarily
      develop a postoperative overcorrected high AC/A ratio esotropia.

PMID- 14653775
TI  - Major review: The underutilization of vision screening (for amblyopia, optical
      anomalies and strabismus) among preschool age children.
AB  - BACKGROUND: Nearly 80% of preschool age children never get an eye examination
      (1). Many "back to school" physical exams do not test for common vision
      disorders. Untreated eye and vision problems can interfere with most life
      experiences. The prevalence of undetected vision problems among preschool age
      children is estimated to be 5% to 10% (2). Failure to detect visual impairment
      early may have a permanent effect on long term vision outcomes, education
      achievement, and self esteem (3). The most common vision disorders among children
      are strabismus, amblyopia and optical problems impairing visual acuity and depth
      perception. Various professional organizations, including the American Academy of
      Pediatrics (AAP), advise preschool vision screening to detect and correct vision
      problems before school entry. The AAP also recommends that children continue to
      receive periodic eye and vision examinations throughout childhood. However,
      resources for this level of care are rarely available. As such, only 21% of
      preschool age children receive vision screening and even fewer children get a
      comprehensive eye examination (1). PURPOSE: The purpose of this review is to
      determine, through a critical review of the literature, the social, economic, and
      political barriers which contribute to the underutilization of vision screening
      among preschool age children. A secondary aim is to identify gaps in the
      literature base that may be needed to complete a public policy response to this
      problem. METHOD: A comprehensive review and analysis of the pertinent available
      literature. RESULTS: A variety of barriers exist which prevent children from
      receiving proper vision screening. They include social, economic and even
      political problems. Social contextual barriers include ignorance, inconvenience,
      language, and a lack of providers. Financial barriers affect low income families.
      Political barriers reside in the disproportionately meager funding of
      preventative medicine. Moreover there are additional factors which put
      preventative medicine for vision at a disadvantage compared to other pediatric
      demands like immunizations, such as the danger to both the individual and society
      from the medical condition being prevented. CONCLUSION: Even considering large
      gaps in the literature concerning this topic, it is clear that low income,
      minority, uninsured families are at high risk of not utilizing vision screening.
      Ignorance remains a major problem at all levels so improvements in the
      distribution of information and education are needed and should yield
      improvement. Additional funding is necessary to pay for these remedies. Titration
      and direction of available resources to those at highest risk will create the
      greatest return on such efforts.

PMID- 14653776
TI  - The efficacy of photoscreening for amblyopiagenic factors in a high risk
      population.
AB  - BACKGROUND: Amblyopia is the leading cause of monocular "legal" blindness in
      children and young adults, affecting 3% to 5% of the population. Factors
      producing amblyopia can be detected through a complete eye examination. Although
      it is important to treat children at risk for amblyopia as early as possible,
      appropriate screening methods for severely impaired individuals are lacking. The
      purpose of this study was to assess the ability of a photoscreening camera to
      detect amblyopiagenic factors (strabismus, unequal refractive error, and media
      opacities) in a group of disabled children, who were currently unscreenable with
      standard methodology. METHODS: Fifty-four high risk individuals, 6-20 years in
      age, were evaluated for amblyopiagenic factors using the MTI photoscreening
      camera, pre- and post-cycloplegia. The "gold standard" for comparison was a
      concurrent complete eye examination, including ocular health, visual acuity
      estimation, motility, ophthalmoscopy and clinical cycloplegic refractive error
      determination. Criteria for a "failure" on the clinical examination included
      myopia greater than -1.00 diopters (D), hyperopia greater than +3.00 D (2-6
      years) and greater than +2 D (over 6 years), astigmatism greater than 1.5 D,
      unequal refractive error greater than 1.5 D, any strabismus, or any media
      opacity. RESULTS: Fifty- four individuals with disabilities, deemed untestable by
      standard vision screenings, were evaluated. The number of children with
      amblyopiagenic factors by complete cycloplegic ophthalmologic examination was 30
      (55%) and by photoscreening was 25 (46%). Using the MTI photoscreener, the
      sensitivity was determined to be 83% with a specificity of 79%. The positive and
      negative predictive values of photoscreening were 83% and 79% respectively.
      CONCLUSIONS: The MTI photoscreener can detect such amblyopiagenic factors as high
      refractive error, strabismus, unequal refractive error, and significant media
      opacity. Photoscreening is an excellent way of obtaining valid vision screening
      with limited patient cooperation. Using photoscreening data, proper referrals can
      be made and prioritized for disabled individuals.

PMID- 14653777
TI  - Stereopsis in idiopathic macular hole with special reference to the size of the
      hole and its effect on stereoacuity.
AB  - PURPOSE: To identify the characteristics of binocular vision in unilateral
      idiopathic macular hole (MH) regarding the size of the hole and its effect on
      stereopsis. SUBJECTS AND METHODS: Twelve patients with idiopathic MH were tested
      using the Amsler Grid, Bagolini Striated Glasses, Starlight Test, Titmus
      Stereotest (the Titmus) and Lang Stereotest (the Lang). The results were analyzed
      with reference to two parameters: visual acuity and the size of the MH. RESULTS:
      The size of the MH in 12 subjects ranged from 0.67 degrees to 2.13 degrees (mean,
      1.29 degrees). The MHs caused distorted central vision under binocular
      conditions. Visual acuities ranged from 0.3 to 0.06. Nine out of the 12 patients
      (75%) failed the 800 seconds of arc (") with the Titmus, but all 12 patients
      (100%) demonstrated stereoacuity of 550" to 600" with the Lang. CONCLUSION: The
      discrepancy of measured stereoacuity between the Titmus and the Lang was
      hypothesized to be due to the different size of the test charts and their targets
      and the pattern of the visual deficit. The pass rate of 92% (550") with the Lang
      is better than rates for other patients with higher visual acuities, such as
      children with amblyopia (62-70%) or adults undergoing visual screening (67%). In
      cases of MH, intact overlapped visual field beyond the central 0-2 degrees played
      an important role in maintaining stereoscopic vision.

PMID- 14653778
TI  - Further followup: (Part IV) A case of acute loss of binocular vision and
      stereoscopic depth perception.
AB  - (Combined case report followup) This is a continuation of a personal report by a
      knowledgeable vision scientist, of the loss of binocular vision due to a major
      vitreous hemorrhage. Please see the initial report for further details. (Romano
      PE. A case of acute loss of binocular vision and stereoscopic depth perception.
      (The misery of acute monovision, having been binocular for 68 years) Binocul Vis
      Strabismus Q 2003; 18:51-55; and followup Binocul Vis Strabismus Q 2003; 18:101
      103, Binocul Vis Strabismus Q 2003; 18:174-175. This report covers months nine
      and ten following the hemorrhage. In the two months since the last report, Visual
      acuity continues to improve to 20/20 with correction, one line less than the
      fellow eye. Residual ring shaped floaters only occasionally interfere with visual
      function which is normal now for virtually all extents and purposes. The
      previously reported observation that binocular ocular sighting dominance is gaze
      dependent is confirmed by prior recently published research: Khan AZ, Crawford
      JD. Ocular dominance reverses as a function of horizontal gaze angle. Vision
      Research 2001; 41:1743-1748.

PMID- 14653779
TI  - The inhibitor ABIN-2 disrupts the interaction of receptor-interacting protein
      with the kinase subunit IKKgamma to block activation of the transcription factor
      NF-kappaB and potentiate apoptosis.
AB  - NF-kappaB (nuclear factor kappaB) proteins are key transcription factors that
      regulate gene expression in response to various extracellular stimuli. The
      pathway leading to the activation of NF-kappaB involves a complicated network
      that includes a number of signalling molecules. The recent identification of a
      wide range of negative regulators of NF-kappaB has given another layer of
      complexity in NF-kappaB activation. We and others have previously identified the
      protein ABIN-2 (A20 binding inhibitor of NF-kappaB 2) as an inhibitor of NF
      kappaB activation. In the present paper, we demonstrate that ABIN-2 exerts its
      inhibitory function by blocking the interaction of RIP (receptor-interacting
      protein) with the downstream effector IKKgamma, a non-kinase component of the
      IkappaB (inhibitory kappaB) kinase complex. When overexpressed in cells, ABIN-2
      bound to IKKgamma and prevented the association of IKKgamma with RIP. By a
      deletion mapping, a stretch of 50 amino acids on ABIN-2 is found to be essential
      for its interaction with IKKgamma. The ABIN-2 mutant that lacked these 50 amino
      acids did not interact with IKKgamma and, consequently, failed to inhibit NF
      kappaB activation. Strikingly, a portion of RIP, which is similar to this 50
      residue domain of ABIN-2, is also essential for RIP interaction with IKKgamma.
      The RIP mutant with deletion of this similar region did not associate with
      IKKgamma and had substantial reduction of its ability to mediate NF-kappaB
      activation. Taken together, these conserved 50 residues of ABIN-2 and RIP define
      a novel structural domain in mediating a key step in the NF-kappaB signalling
      pathway through the interaction with IKKgamma. Finally, the signalling pathway of
      NF-kappaB activation is known to promote survival in many cellular events. The
      mechanism for decision between cell death and survival is under fine regulation.
      In the present paper, we demonstrated further that the expression of ABIN-2 could
      promote the RIP-mediated apoptosis by presumably suppressing the anti-apoptotic
      effect of NF-kappaB.

PMID- 14653780
TI  - Plant sterol biosynthesis: identification of two distinct families of sterol
      4alpha-methyl oxidases.
AB  - In plants, the conversion of cycloartenol into functional phytosterols requires
      the removal of the two methyl groups at C-4 by an enzymic complex including a
      sterol 4alpha-methyl oxidase (SMO). We report the cloning of candidate genes for
      SMOs in Arabidopsis thaliana, belonging to two distinct families termed SMO1 and
      SMO2 and containing three and two isoforms respectively. SMO1 and SMO2 shared low
      sequence identity with each other and were orthologous to the ERG25 gene from
      Saccharomyces cerevisiae which encodes the SMO. The plant SMO amino acid
      sequences possess all the three histidine-rich motifs (HX3H, HX2HH and HX2HH),
      characteristic of the small family of membrane-bound non-haem iron oxygenases
      that are involved in lipid oxidation. To elucidate the precise functions of SMO1
      and SMO2 gene families, we have reduced their expression by using a VIGS (virus
      induced gene silencing) approach in Nicotiana benthamiana. SMO1 and SMO2 cDNA
      fragments were inserted into a viral vector and N. benthamiana inoculated with
      the viral transcripts. After silencing with SMO1, a substantial accumulation of
      4,4-dimethyl-9beta,19-cyclopropylsterols (i.e. 24-methylenecycloartanol) was
      obtained, whereas qualitative and quantitative levels of 4alpha-methylsterols
      were not affected. In the case of silencing with SMO2, a large accumulation of
      4alpha-methyl-Delta7-sterols (i.e. 24-ethylidenelophenol and 24-ethyllophenol)
      was found, with no change in the levels of 4,4-dimethylsterols. These clear and
      distinct biochemical phenotypes demonstrate that, in contrast with animals and
      fungi, in photosynthetic eukaryotes, these two novel families of cDNAs are coding
      two distinct types of C-4-methylsterol oxidases controlling the level of 4,4
      dimethylsterol and 4alpha-methylsterol precursors respectively.

PMID- 14653784
TI  - Unexpected patterns of genetic structuring among locations but not colour morphs
      in Acropora nasuta (Cnidaria; Scleractinia).
AB  - Symbiotic relationships have contributed greatly to the evolution and maintenance
      of biological diversity. On the Great Barrier Reef, species of obligate coral
      dwelling fishes (genus Gobiodon) coexist by selectively recruiting to colonies of
      Acropora nasuta that differ in branch-tip colour. In this study, we investigate
      genetic variability among sympatric populations of two colour morphs of A. nasuta
      ('blue-tip' and 'brown-tip') living in symbiosis with two fish species, Gobiodon
      histrio and G. quinquestrigatus, respectively, to determine whether gobies are
      selecting between intraspecific colour polymorphisms or cryptic coral species. We
      also examine genetic differentiation among coral populations containing both
      these colour morphs that are separated by metres between local sites, tens of
      kilometres across the continental shelf and hundreds of kilometres along the
      Great Barrier Reef. We use three nuclear DNA loci, two of which we present here
      for the first time for Acropora. No significant genetic differentiation was
      detected between sympatric colour morphs at these three loci. Hence, symbiotic
      gobies are selecting among colour morphs of A. nasuta, rather than cryptic
      species. Significant genetic geographical structuring was observed among
      populations, independent of colour, at regional (i.e. latitudinal separation by <
      500 km) and cross-shelf (< 50 km) scales, alongside relative homogeneity between
      local populations on within reef scales (< 5 km). This contrasts with the
      reported absence of large-scale genetic structuring in A. valida, which is a
      member of the same species group as A. nasuta. Apparent differences in
      biogeographical structuring between species within the A. nasuta group emphasize
      the need for comparative sampling across both spatial (i.e. within reefs, between
      reefs and between regions) and taxonomic scales (i.e. within and between closely
      related species).

PMID- 14653781
TI  - Targeting of calcium/calmodulin-dependent protein kinase II.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) has diverse roles in
      virtually all cell types and it is regulated by a plethora of mechanisms. Local
      changes in Ca2+ concentration drive calmodulin binding and CaMKII activation.
      Activity is controlled further by autophosphorylation at multiple sites, which
      can generate an autonomously active form of the kinase (Thr286) or can block
      Ca2+/calmodulin binding (Thr305/306). The regulated actions of protein
      phosphatases at these sites also modulate downstream signalling from CaMKII. In
      addition, CaMKII targeting to specific subcellular microdomains appears to be
      necessary to account for the known signalling specificity, and targeting is
      regulated by Ca2+/calmodulin and autophosphorylation. The present review focuses
      on recent studies revealing the diversity of CaMKII interactions with proteins
      localized to neuronal dendrites. Interactions with various subunits of the NMDA
      (N-methyl-D-aspartate) subtype of glutamate receptor have attracted the most
      attention, but binding of CaMKII to cytoskeletal and several other regulatory
      proteins has also been reported. Recent reports describing the molecular basis of
      each interaction and their potential role in the normal regulation of synaptic
      transmission and in pathological situations are discussed. These studies have
      revealed fundamental regulatory mechanisms that are probably important for
      controlling CaMKII functions in many cell types.

PMID- 14653785
TI  - The genetic pattern of population threat and loss: a case study of butterflies.
AB  - Recent decreases in biodiversity in Europe are commonly thought to be due to land
      use and climate change. However, the genetic diversity of populations is also
      seen as one essential factor for their fitness. Genetic diversity in species
      across the continent of Europe has been recognized as being in part a consequence
      of ice age isolation in southern refugia and postglacial colonization northwards,
      and these phylogeographical patterns may themselves affect the adaptability of
      populations. Recent work on butterfly species with different refugia,
      colonization paths and genetic structures allows this idea to be examined. The
      'chalk-hill blue' pattern is one of decreasing genetic diversity from south to
      north, whereas the 'woodland ringlet' pattern shows greater genetic diversity in
      eastern than in western lineages. Comparison of population demographic trends in
      species with these biogeographical patterns reveals higher rates of decrease with
      lower genetic diversity. This indicates reduced adaptability due to genetic
      impoverishment as a result of glacial and postglacial range changes. Analysis of
      phylogeographical pattern may be a useful guide to interpreting demographic
      trends and in conservation planning.

PMID- 14653786
TI  - Population genetic structure of the sugar beet cyst nematode Heterodera
      schachtii: a gonochoristic and amphimictic species with highly inbred but weakly
      differentiated populations.
AB  - The sugar beet cyst nematode Heterodera schachtii is a soil-dwelling
      phytoparasitic nematode that feeds on beet roots. It is an important pest in most
      sugar beet growing areas, and better knowledge of its genetic variability is an
      important step to preserve the durability of resistant sugar beet varieties. The
      population genetic structure of this species in northern France was studied using
      five microsatellite markers. A hierarchical sampling design was used to
      investigate spatial structuring at the scale of the region, the field and the
      plant. Multilocus genotypes were obtained for single individual second-stage
      larvae, using only one individual per cyst in order to avoid the analysis of
      closely allied individuals (larvae from the same cyst share at least the same
      mother). A consistent trend of heterozygote deficit at all loci was observed at
      all spatial scales. Heterozygote deficit at the level of individual plants argues
      against its generation through a Wahlund effect. Inbreeding could be due to very
      limited active dispersal of larvae in the soil, favouring mating between
      siblings, such as larvae emerging from the same cyst. Such behaviour could have
      important consequences for the evolution of virulence in increasing the
      production of homozygous virulent individuals. Moreover, an analysis of molecular
      variance (amova) reveals that only 1.6% of the genetic variability is observed
      among regions, 3.7% among fields of the same region and 94.6% within fields. The
      very low level of genetic differentiation among fields is also indicated by low
      values of FST (</= 0.105) even for fields 150 km apart. We suggest that long
      distance gene flows occur due to passive transport of cysts by human activities,
      water or wind. As such mechanisms of gene flow would involve cysts and not
      larvae, the strong signals of inbreeding observed at the local scale should not
      be disrupted. To our knowledge, this study constitutes the first investigation of
      the genetic structure of a phytoparasitic nematode based on neutral codominant
      genetic markers scored in single individuals.

PMID- 14653787
TI  - Mitochondrial control region diversity of the houbara bustard Chlamydotis
      undulata complex and genetic structure along the Atlantic seaboard of North
      Africa.
AB  - The houbara bustard, Chlamydotis undulata, is a declining cryptic desert bird
      whose range extends from North Africa to Central Asia. Three subspecies are
      currently recognized by geographical distribution and morphology:
      C.u.fuertaventurae, C.u.undulata and C.u.macqueenii. We have sequenced 854 bp of
      mitochondrial control region from 73 birds to describe their population genetic
      structure with a particular sampling focus on the connectivity between
      C.u.fuertaventurae and C.u.undulata along the Atlantic seaboard of North Africa.
      Nucleotide and haplotypic diversity varied among the subspecies being highest in
      C.u.undulata, lowest in C.u.fuertaventurae and intermediate in C.u.macqueenii.
      C.u.fuertaventurae and C.u.undulata are paraphyletic and an average nucleotide
      divergence of 2.08% splits the later from C.u.macqueenii. We estimate that
      C.u.fuertaventurae and C.u.undulata split from C.u.macqueenii approximately 430
      000 years ago. C.u.fuertaventurae and C.u.undulata are weakly differentiated (FST
      = 0.27, Nm = 1.3), indicative of a recent shared history. Archaeological evidence
      indicates that houbara bustards have been present on the Canary Islands for 130
      170 000 years. However, our genetic data point to a more recent separation of
      C.u.fuertaventurae and C.u.undulata at around 20-25 000 years. Concordant
      archaeological, climatic opportunities for colonization and genetic data point to
      a scenario of: (i) initial colonization of the Canary Islands about 130 000 years
      ago; (ii) a period of secondary contact 19-30 000 years ago homogenizing any pre
      existing genetic structure followed by; (iii) a period of relative isolation that
      persists today.

PMID- 14653788
TI  - Genetic assignment methods for the direct, real-time estimation of migration
      rate: a simulation-based exploration of accuracy and power.
AB  - Genetic assignment methods use genotype likelihoods to draw inference about where
      individuals were or were not born, potentially allowing direct, real-time
      estimates of dispersal. We used simulated data sets to test the power and
      accuracy of Monte Carlo resampling methods in generating statistical thresholds
      for identifying F0 immigrants in populations with ongoing gene flow, and hence
      for providing direct, real-time estimates of migration rates. The identification
      of accurate critical values required that resampling methods preserved the
      linkage disequilibrium deriving from recent generations of immigrants and
      reflected the sampling variance present in the data set being analysed. A novel
      Monte Carlo resampling method taking into account these aspects was proposed and
      its efficiency was evaluated. Power and error were relatively insensitive to the
      frequency assumed for missing alleles. Power to identify F0 immigrants was
      improved by using large sample size (up to about 50 individuals) and by sampling
      all populations from which migrants may have originated. A combination of
      plotting genotype likelihoods and calculating mean genotype likelihood ratios
      (DLR) appeared to be an effective way to predict whether F0 immigrants could be
      identified for a particular pair of populations using a given set of markers.

PMID- 14653789
TI  - Consequences of unequal population size, asymmetric gene flow and sex-biased
      dispersal on population structure in brook charr (Salvelinus fontinalis).
AB  - Unravelling relationships between dispersal and population structure requires
      considering the impacts of assumption violations of indirect gene flow models in
      a given system. We combined temporal, individual and coalescent-based analyses of
      microsatellite DNA variation to explore the general hypothesis that unequal
      effective population size (Ne), asymmetric gene flow (m) and nonrandom (sex
      biased) individual dispersal had an important effect on spatiotemporal population
      structuring in lake-dwelling brook charr (Salvelinus fontinalis). This
      integrative examination shed light on the dichotomous structuring observed
      between an outlet and three tributary-spawning populations and their potential
      for adaptive divergence. It revealed further that finer tributary population
      structuring incongruent with drainage structure has been shaped by asymmetric m
      from one population with a large Ne towards two populations of smaller Ne. Gene
      flow among the tributaries was also mediated mainly by male-biased dispersal.
      However, longer distance dispersal from tributaries to the outflow was female
      biased. Spatially dependent sex-biased dispersal may have contributed therefore
      to gene flow at different levels of population structuring. Our results
      demonstrate how dispersal and population structure may interrelate to produce
      spatial variation in intraspecific diversity, and are therefore relevant for
      conservation programmes seeking to define conservation units or predict
      recolonization rates of extirpated populations.

PMID- 14653790
TI  - Amplified fragment length polymorphism versus random amplified polymorphic DNA
      markers: clonal diversity in Saxifraga cernua.
AB  - Random amplified polymorphic DNA (RAPD) markers are sensitive to changes in
      reaction conditions and may express polymorphisms of nongenetic origin. Taxa with
      variable chromosome numbers are particularly challenging cases, as differences in
      DNA content may also influence marker reproducibility. We addressed these
      problems by comparing RAPD and amplified fragment length polymorphism (AFLP)
      analyses of clonal identity and relationships in a chromosomally variable arctic
      plant, the polyploid Saxifraga cernua, which has been thought to be monoclonal
      over large geographical distances. Fifty-seven plants from four Greenland
      populations were analysed using a conservative scoring approach. In total, 26
      AFLP and 32 RAPD multilocus phenotypes (putative clones) were identified, of
      which 21 were identical and each of the remaining five AFLP clones was split into
      two to three very similar RAPD clones. This minor difference can be explained by
      sampling error and stochastic variation. The pattern observed in Greenland
      corroborates our previous results from Svalbard, suggesting that rare sexual
      events in S. cernua are sufficient to maintain high levels of clonal diversity
      even at small spatial scales. We conclude that although AFLP analysis is superior
      in terms of efficiency, RAPDs may still be used as reliable markers in small low
      tech laboratories.

PMID- 14653791
TI  - Circum Black Sea phylogeography of Barbus freshwater fishes: divergence in the
      Pontic glacial refugium.
AB  - We used DNA sequence variation at the mitochondrial cytochrome b gene (1141 bp)
      to assess the phylogeography of Barbus fishes in the Black Sea region. Our aim
      was to test whether the recent ( approximately 22 000-7500 years ago) freshwater
      phase of the Black Sea was a conduit for gene flow among freshwater fishes that
      today are found in streams entering the saltwater Black Sea. Deep
      phylogeographical breaks suggestive of allopatric divergence were observed
      between four regional groups of populations. Coalescent simulation used to
      distinguish between this and an alternative scenario that the phylogeographical
      structure was due to random lineage sorting showed that the contemporary
      populations were unlikely (P < 0.001) to have been founded by a single ancestral
      population. Divergences between the lineages (0.86-2.54%) were dated to the
      Middle to Late Pleistocene using distances and a molecular clock corrected for
      superimposed substitutions. Taken together, this evidence suggests that multiple
      refugial populations survived over several later glaciations in the vicinity of
      the Black Sea. This Pontic refugium served as the primary source for the
      postglacial expansion throughout Europe as far as the Atlantic basin. However,
      only one of the phylogeographical lineages contributed to this dispersion,
      whereas the others remain restricted to the Black Sea region and followed
      independent evolutionary trajectories.

PMID- 14653792
TI  - Mitochondrial DNA variation in North American populations of Daphnia obtusa:
      continentalism or cryptic endemism?
AB  - The morphological stasis of many freshwater crustaceans has resulted in the prior
      delineation of cosmopolitan species and has been explained by their capacity for
      long-distance dispersal. This study examines the phylogeography of Daphnia
      obtusa, a cladoceran thought to be widespread in North America. However, sequence
      variation of the mitochondrial cytochrome c oxidase subunit I gene indicates that
      this taxon is composed of two morphologically cryptic species, designated D.
      obtusa NA1 and NA2. NA2 is restricted to the east, whereas NA1 is broadly
      distributed across the United States, and is subdivided into four phylogroups
      that show weak genetic differentiation over broad geographical areas, which
      likely reflects recent long-distance dispersal. The current distributions of the
      four phylogroups in NA1 can be explained by recent range expansion from different
      refugia following the last Pleistocene glacial advance. Interestingly, the
      mitochondrial phylogroups identified in this study do not correspond to lineages
      detected in a previous allozyme analysis. However, the latter groups are
      associated with a habitat shift suggesting that natural selection may have played
      a role in their divergence. The results of this and previous studies illustrate
      the complicated biogeographical history of freshwater cladocerans.

PMID- 14653793
TI  - Phylogeographical history of the sponge Crambe crambe (Porifera,
      Poecilosclerida): range expansion and recent invasion of the Macaronesian islands
      from the Mediterranean Sea.
AB  - We studied sequence variation in the nuclear ribosomal internal transcribed
      spacers (ITS-1 and ITS-2) in 111 individuals from 11 populations/localities of
      the sponge Crambe crambe across the core species range in the western
      Mediterranean Sea and Atlantic Ocean. We report the first confirmed instance of
      intragenomic variation in sponges. Phylogeographical, nested clade and population
      genetic analyses were used to elucidate the species' evolutionary history. The
      study revealed highly structured populations affected by restricted gene flow and
      isolation-by-distance. A contiguous range expansion in the whole distribution
      area of the sponge was inferred. Phylogenetic analyses indicate a recent origin
      of most sequence types that could be explained by a recent origin of the species
      or a by recent bottleneck event in the studied area. A recent expansion of the
      distribution range to the Macaronesian region from the Mediterranean Sea was also
      detected, suggesting that C. crambe was recently introduced from the
      Mediterranean Sea to the Atlantic Ocean via human-mediated transport, and that
      the pattern observed is not the result of a natural biogeographical relationship
      between these zones.

PMID- 14653794
TI  - Multiple hybrid origins, genetic diversity and population genetic structure of
      two endemic Sorbus taxa on the Isle of Arran, Scotland.
AB  - Understanding the processes that have given rise to polyploid hybrid taxa is
      central to our understanding of plant evolution. In this study, we use an array
      of genetic markers in a population analysis to elucidate the hybrid origins of
      the Arran whitebeams Sorbus arranensis and S. pseudofennica, two woody plant taxa
      endemic to the Isle of Arran, Scotland. It has been proposed that S. arranensis
      was derived by hybridization between S. aucuparia and S. rupicola, and that
      subsequent hybridization between S. arranensis and S. aucuparia gave rise to S.
      pseudofennica. Analyses of species-specific isozyme, nuclear intron and
      chloroplast DNA markers confirm the proposed origin of S. arranensis, and
      indicate that S. aucuparia was the female parent in the hybridization. Analysis
      of microsatellite markers suggests that there have been at least three origins of
      S. arranensis on Arran. Microsatellite markers also support the proposed
      hypothesis for the origin of S. pseudofennica, and indicate at least five hybrid
      origins of this taxon. In total, three multilocus genotypes of S. arranensis and
      eight of S. pseudofennica were detected on Arran and multilocus genotypic
      diversity levels Hg were 0.09 and 0.63, respectively. Genetic differentiation
      (thetaST) values based on multilocus genotypes are substantial (0.344 and 0.470
      for S. arranensis and S. pseudofennica, respectively) implying limited seed flow
      among populations. These results indicate that the endemic Sorbus taxa on Arran
      are the products of multiple and ongoing evolutionary events. This information
      must be incorporated into management policies for their future conservation.

PMID- 14653795
TI  - Genetic consequences of Pleistocene glaciations for the tundra vole (Microtus
      oeconomus) in Beringia.
AB  - Repeated glacial events during the Pleistocene fragmented and displaced
      populations throughout the northern continents. Different models of the effects
      of these climate-driven events predict distinct phylogeographic and population
      genetic outcomes for high-latitude faunas. The role of glaciations in (i)
      promoting intraspecific genetic differentiation and (ii) influencing genetic
      diversity was tested within a phylogeographic framework using the rodent Microtus
      oeconomus. The spatial focus for the study was Beringia, which spans eastern
      Siberia and northwestern North America, and was a continental crossroads and
      potential high arctic refugium during glaciations. Variation in mitochondrial DNA
      (cytochrome b and control region; 214 individuals) and nuclear DNA (ALDH1 intron;
      63 individuals) was investigated across the Beringian region. Close genetic
      relationships among populations on either side of the Bering Strait are
      consistent with a history of periodic land connections between North America and
      Asia. A genetic discontinuity observed in western Beringia between members of a
      Central Asian clade and a Beringian clade is geographically congruent with
      glacial advances and with phylogeographic discontinuities identified in other
      organisms. Divergent island populations in southern Alaska were probably
      initially isolated by glacial vicariance, but subsequent differentiation has
      resulted from insularity. Tests of the genetic effects of postglacial
      colonization were largely consistent with expansion accompanied by founder effect
      bottlenecking, which yields reduced diversity in populations from recently
      deglaciated areas. Evidence that populations in the Beringian clade share a
      history of expansion from a low-diversity ancestral population suggests that
      Beringia was colonized by a small founder population from central Asia, which
      subsequently expanded in isolation.

PMID- 14653796
TI  - Molecular systematics and phylogeography of the Plethodon elongatus species
      group: combining phylogenetic and population genetic methods to investigate
      species history.
AB  - Plethodon elongatus and P. stormi (Caudata: Plethodontidae) are Pacific Northwest
      endemic species which occur in northwestern California and southwestern Oregon.
      Studies on these salamanders have resulted in differing taxonomic conclusions,
      but the underlying historical hypotheses, at both inter- and intraspecific
      levels, have never been examined in a molecular framework. Here, representatives
      of 81 populations from throughout the range of both taxa are sequenced. Portions
      of three mitochondrial protein-coding genes (cytochrome b, NADH dehydrogenase
      subunit 4, and ATPase 6) were sequenced. Four haplotype groups with
      nonoverlapping geographical ranges were recovered in separate and combined
      analyses of the data. One clade corresponds to the distribution of P. stormi,
      while the remaining three comprise P. elongatus. Phylogenetic relationships among
      haplotype groups differ in separate analyses of the genes but converge on a well
      supported topology, with P. elongatus and P. stormi as monophyletic sister taxa,
      in combined Maximum Parsimony and Maximum Likelihood analyses. Population genetic
      analyses of mismatch distributions and Tajima's D-statistic are consistent with
      range expansion for the largest clade within P. elongatus, covering the northern
      two-thirds of the species range. In contrast, the P. stormi haplotype clade and
      the P. elongatus clade from the southern third of the species range may have been
      relatively stable. Morphological boundaries between P. elongatus and P. stormi
      are largely congruent with mitochondrial DNA breaks and continued treatment as
      sister taxa is supported. Although mitochondrial DNA haplotype groups may reflect
      historical separation within P. elongatus, genetic barriers are incongruent with
      intraspecific patterns of morphological variation.

PMID- 14653797
TI  - Extensive sharing of chloroplast haplotypes among European birches indicates
      hybridization among Betula pendula, B. pubescens and B. nana.
AB  - Extensive sharing of chloroplast haplotypes among the silver birch, Betula
      pendula Roth., the downy birch, B. pubescens Ehrh., and the dwarf birch, B. nana
      L., was discovered using polymerase chain reaction-restriction fragment length
      polymporphism markers. The geographical component of the genetic variation was
      stronger than the species component: the species were not significantly different
      while 11% of the variation could be attributed to differentiation between the two
      main regions studied, Scandinavia and western Russia. All haplotypes occurring in
      more than 2% of the individuals were shared among the species and the
      introgression ratios were quite large: 0.79 between B. pubescens and B. pendula
      and 0.67 between B. pubescens and B. nana. The data also indicate that B. pendula
      individuals are more similar to sympatric B. pubescens than to B. pendula
      individuals from nearby forests. However, this trend is not as pronounced when B.
      pubescens is considered, suggesting that introgression is not symmetrical. The
      haplotype sharing among the three Betula species is most likely caused by
      hybridization and subsequent cytoplasmic introgression.

PMID- 14653798
TI  - Speciation of Iberian diving beetles in Pleistocene refugia (Coleoptera,
      Dytiscidae).
AB  - The Mediterranean basin is an area of high diversity and endemicity, but the age
      and origin of its fauna are still largely unknown. Here we use species-level
      phylogenies based on approximately 1300 base pairs of the genes 16S rRNA and
      cytochrome oxidase I to establish the relationships of 27 of the 34 endemic
      Iberian species of diving beetles in the family Dytiscidae, and to investigate
      their level of divergence. Using a molecular clock approach, 18-19 of these
      species were estimated to be of Pleistocene origin, with four to six of them from
      the Late Pleistocene ( approximately 100 000 years). A second, lower speciation
      frequency peak was assigned to Late Miocene or Early Pliocene. Analysis of the
      distributional ranges showed that endemic species placed in the tip nodes of the
      trees are significantly more likely to be allopatric with their sisters than
      endemic species at lower node levels. Allopatric sister species are also
      significantly younger than sympatric clades, in agreement with an allopatric mode
      of speciation and limited subsequent range movement. These results strongly
      suggest that for some taxa Iberian populations were isolated during the
      Pleistocene long enough to speciate, and apparently did not expand their ranges
      to recolonize areas north of the Pyrenees. This is in contradiction to
      observations from fossil beetles in areas further north, which document large
      range movements associated with the Pleistocene glacial cycles hypothesized to
      suppress population isolation and allopatric speciation.

PMID- 14653799
TI  - Body size, age and paternity in common brushtail possums (Trichosurus vulpecula).
AB  - Sexual selection should produce sexual size dimorphism in species where larger
      members of one sex obtain disproportionately more matings. Recent theory suggests
      that the degree of sexual size dimorphism depends on physical and temporal
      constraints involving the operational sex ratio, the potential reproductive rate
      and the trade-off between current reproductive effort and residual reproductive
      value. As part of a large-scale experiment on dispersal, we investigated the
      mating system of common brushtail possums inhabiting old-growth Eucalyptus forest
      in Australia. Paternity was assigned to 20 of 28 pouch-young (maternity known)
      genotyped at six microsatellite loci. Male mating success was strongly related to
      body size and age; male body weight and age being highly correlated. Despite
      disproportionate mating success favouring larger males, sexual size dimorphism
      was only apparent among older animals. Trapping and telemetry indicated that the
      operational sex ratio was effectively 1 : 1 and the potential reproductive rate
      of males was at most four times that of females. Being larger appeared to entail
      significant survival costs because males 'died-off' at the age at which sexual
      size dimorphism became apparent (8-9 years). Male and female home ranges were the
      same size and males appeared to be as sedentary as females. Moreover, longevity
      appears to be only slightly less important to male reproductive success than it
      is to females. It is suggested that a sedentary lifestyle and longevity are the
      key elements constraining selection for greater sexual size dimorphism in this
      'model' medium-sized Australian marsupial herbivore.

PMID- 14653800
TI  - Significant reproductive skew in the facultatively polygynous ant Pheidole
      pallidula.
AB  - Reproductive skew - the extent to which reproduction is unevenly shared between
      individuals in a social group - varies greatly between and within animal species.
      In this study, we investigated how queens share parentage in polygynous (multiple
      queen) colonies of the Mediterranean ant Pheidole pallidula. We used highly
      polymorphic microsatellites markers to determine parentage of gynes (new queens),
      males and workers in P. pallidula field colonies. The comparison of the genotypes
      of young and adult workers revealed a very low queen turnover (less than 2%). The
      first main finding of the study of reproductive skew in these colonies was that
      there was a significant departure from equal contribution of queens to gyne, male
      and worker production. Reproductive skew was greater for male production than for
      queen and worker production. There was no relationship between the magnitude of
      the reproductive skew and the number of reproductive queens per colony, their
      relatedness and the overall colony productivity, some of the factors predicted to
      influence the extent of reproductive skew. Finally, our study revealed for the
      first time a trade-off in the relative contribution of nestmate queens to gyne
      and worker production. The queens contributing more to gyne production
      contributed significantly less to worker production.

PMID- 14653801
TI  - Genetic structure of the forest herb Primula elatior in a changing landscape.
AB  - To investigate whether changes in land use and associated forest patch turnover
      affected genetic diversity and structure of the forest herb Primula elatior,
      historical data on landscape changes were combined with a population genetic
      analysis using dominant amplified fragment length polymorphism markers. Based on
      nine topographic maps, landscape history was reconstructed and forest patches
      were assigned to two age classes: young (less than 35 years) and old (more than
      35 years). The level of differentiation among Primula populations in recently
      established patches was compared with the level of differentiation among
      populations in older patches. Genetic diversity was independent of population
      size (P > 0.05). Most genetic variation was present within populations. Within
      population diversity levels tended to be higher for populations located in older
      forests compared with those for populations located in young forests (Hj = 0.297
      and 0.285, respectively). Total gene diversity was also higher for old than for
      young populations (Ht = 0.2987 and 0.2828, respectively). The global fixation
      index FST averaged over loci was low, but significant. Populations in older
      patches were significantly more differentiated from each other than were
      populations in recently established patches and they showed significant isolation
      by distance. In contrast, no significant correlations between pairwise
      geographical distance and FST were found for populations in recently established
      patches. The location of young and old populations in the studied system and
      altered gene flow because of increased population density and decreased inter
      patch distances between extant populations may explain the observed lower genetic
      differentiation in the younger populations. This study exemplifies the importance
      of incorporating data on historical landscape changes in population genetic
      research at the landscape scale.

PMID- 14653802
TI  - The use of reference strand-mediated conformational analysis for the study of
      cheetah (Acinonyx jubatus) feline leucocyte antigen class II DRB polymorphisms.
AB  - There is now considerable evidence to suggest the cheetah (Acinonyx jubatus) has
      limited genetic diversity. However, the extent of this and its significance to
      the fitness of the cheetah population, both in the wild and captivity, is the
      subject of some debate. This reflects the difficulty associated with establishing
      a direct link between low variability at biologically significant loci and
      deleterious aspects of phenotype in this, and other, species. Attempts to study
      one such region, the feline leucocyte antigen (FLA), are hampered by a general
      reliance on cloning and sequencing which is expensive, labour-intensive, subject
      to PCR artefact and always likely to underestimate true variability. In this
      study we have applied reference strand-mediated conformational analysis (RSCA) to
      determine the FLA-DRB phenotypes of 25 cheetahs. This technique was rapid,
      repeatable and less prone to polymerase chain reaction (PCR)-induced sequence
      artefacts associated with cloning. Individual cheetahs were shown to have up to
      three FLA-DRB genes. A total of five alleles were identified (DRB*ha14-17 and
      DRB*gd01) distributed among four genotypes. Fifteen cheetahs were
      DRB*ha14/ha15/ha16/ha17, three were DRB*ha15/ha16/ha17, six were
      DRB*ha14/ha16/ha17 and one was DRB*ha14/ha15/ha16/ha17/gd01. Sequence analysis of
      DRB*gd01 suggested it was a recombinant of DRB*ha16 and DRB*ha17. Generation of
      new alleles is difficult to document, and the clear demonstration of such an
      event is unusual. This study confirms further the limited genetic variability of
      the cheetah at a biologically significant region. RSCA will facilitate large
      scale studies that will be needed to correlate genetic diversity at such loci
      with population fitness in the cheetah and other species.

PMID- 14653803
TI  - The last common ancestor of Sarcolaenaceae and Asian dipterocarp trees was
      ectomycorrhizal before the India-Madagascar separation, about 88 million years
      ago.
AB  - Phylogenetic studies comparing the Dipterocarpaceae and the Sarcolaenaceae, a
      tree family endemic to Madagascar, have shown that the Sarcolaenaceae share a
      common ancestor with Asian dipterocarps. This suggests that Asian dipterocarps
      drifted away from Madagascar with the India-Seychelles landmass and then
      dispersed through Asia. Although all dipterocarps examined so far have been found
      to be ectomycorrhizal, the ectomycorrhizal status of Sarcolaenaceae had not been
      investigated. Here we establish the ectomycorrhizal status of Sarcolaenaceae
      using histological and molecular methods. This indicates that the common ancestor
      of the Sarcolaenaceae and Asian dipterocarps was ectomycorrhizal, at least before
      the separation of the Madagascar-India landmass, 88 million years ago.

PMID- 14653804
TI  - Stable Bacillus thuringiensis (Bt) toxin content in interspecific F1 and
      backcross populations of wild Brassica rapa after Bt gene transfer.
AB  - Stable expression of a transgene may lead to increased fitness for wild plants
      after acquiring the transgene via crop-weed hybridization. Here, we investigate
      the stability of Bt toxin content in wild Brassica rapa acquiring the Bt gene
      from Bt Brassica napus. The Bt toxin content in nine Bt-expressing B. napus lines
      was 0.80-1.70 micro g/g leaf tissue throughout the growing season. These nine
      lines were crossed with three accessions of wild B. rapa and the Bt gene was
      successfully transferred to interspecific hybrids (F1) and successive backcross
      generations (BC1 to BC4). The Bt toxin level in F1 and BC progenies containing
      the Bt gene remained at 0.90-3.10 micro g/g leaf tissue. This study indicates
      that the Bt gene can persist and be stably expressed in wild B. rapa.

PMID- 14653806
TI  - The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins
      and molecular functions.
AB  - The protein tyrosine phosphatase PTP-Basophil (PTP-Bas) and its mouse homologue,
      PTP-Basophil-like (PTP-BL), are high molecular mass protein phosphatases
      consisting of a number of diverse protein-protein interaction modules. Several
      splicing variants of these phosphatases are known to exist thus demonstrating the
      complexity of these molecules. PTP-Bas/BL serves as a central scaffolding protein
      facilitating the assembly of a multiplicity of different proteins mainly via five
      different PDZ domains. Many of these interacting proteins are implicated in the
      regulation of the actin cytoskeleton. However, some proteins demonstrate a
      nuclear function of this protein tyrosine phosphatase. PTP-Bas is involved in the
      regulation of cell surface expression of the cell death receptor, Fas. Moreover,
      it is a negative regulator of ephrinB phosphorylation, a receptor playing an
      important role during development. The phosphorylation status of other proteins
      such as RIL, IkappaBalpha and beta-catenin can also be regulated by this
      phosphatase. Finally, PTP-BL has been shown to be involved in the regulation of
      cytokinesis, the last step in cell division. Although the precise molecular
      function of PTP-Bas/BL is still elusive, current data suggest clearly that PTP
      Bas/BL belongs to the family of PDZ domain containing proteins involved in the
      regulation of the cytoskeleton and of intracellular vesicular transport
      processes.

PMID- 14653807
TI  - Alternagin-C, a nonRGD-disintegrin, induces neutrophil migration via integrin
      signaling.
AB  - Recently, a new protein containing a disintegrin domain, alternagin-C (Alt-C),
      was purified from Bothrops alternatus venom. Unlike other disintegrins, in Alt-C
      an ECD amino acid mogif takes the place of the RGD sequence. Most disintegrins
      contain an RGD/KGD sequence and are very potent inhibitors of platelet
      aggregation, as well as other cell interactions with the extracellular matrix,
      including tumor cell metastasis and angiogenesis. The present study investigated
      the effects of Alt-C on human neutrophil chemotaxis in vitro and the activation
      of integrin-mediated pathways. Alt-C showed a potent chemotactic effect for human
      neutrophils when compared to N-formyl-methionyl-leucyl-phenylalanine peptide
      (fMLP), a classic chemotactic agent. Moreover, preincubation of neutrophils with
      Alt-C significantly inhibited chemotaxis toward fMLP and itself. In addition, a
      peptide containing an ECD sequence presented a chemotactic activity and
      significantly inhibited chemotaxis induced by Alt-C and fMLP. A significant
      increase of F-actin content was observed in cells treated with Alt-C, showing
      that the chemotactic activity of Alt-C on neutrophils is driven by actin
      cytoskeleton dynamic changes. Furthermore, this protein was able to induce an
      increase of phosphotyrosine content triggering focal adhesion kinase activation
      and its association with phosphatidylinositol 3-kinase. Alt-C was also able to
      induce a significant increase in extracellular signal-regulated kinase 2 nuclear
      translocation. The chemotactic activity of Alt-C was partially inhibited by
      LY294002, a specific phosphatidylinositol 3-kinase inhibitor, and by PD98056, a
      Map kinase kinase inhibitor. These findings suggest that Alt-C can trigger human
      neutrophil chemotaxis modulated by intracellular signals characteristic of
      integrin-activated pathways and that these effects could be related to the ECD
      mogif present in disintegrin-like domain.

PMID- 14653808
TI  - The expression of retinoblastoma and Sp1 is increased by low concentrations of
      cyclin-dependent kinase inhibitors.
AB  - We examined the effect of suboptimal concentrations of cyclin-dependent kinase
      inhibitors, which do not interfere with cell proliferation, on retinoblastoma
      expression in hamster (Chinese hamster ovary K1) and human (K562 and HeLa) cells.
      To achieve this, we used the chemical inhibitors roscovitine and olomoucine
      (which inhibit CDK2 preferentially), UCN-01 (which also inhibits CDK4/6) and p21
      (as an intrinsic inhibitor). All chemical inhibitors and overexpression of p21
      strongly induced retinoblastoma protein expression. UCN-01-mediated
      retinoblastoma expression was caused by an increase in both the levels of
      retinoblastoma mRNA and the stability of the protein. The expression of the
      transcription factor Sp1, a retinoblastoma-interacting protein, was also enhanced
      by all the cyclin-dependent kinase inhibitors tested. However, Sp1 expression was
      caused by an increase in the levels of Sp1 mRNA without modification in the
      stability of the protein. By using luciferase experiments, the transcriptional
      activation of both retinoblastoma and Sp1 promoters by UCN-01 was confirmed.
      Bisindolylmaleimide I, at concentrations causing a similar or higher inhibition
      of protein kinase C than UCN-01, provoked a lower activation of retinoblastoma
      and Sp1 expression. Finally, the effects of cyclin-dependent kinase inhibitors on
      dihydrofolate reductase gene expression were evaluated. Treatment with UCN-01
      increased cellular dihydrofolate reductase mRNA levels, and dihydrofolate
      reductase enzymatic activity was enhanced by UCN-01, roscovitine, olomoucine and
      p21, in transient transfection experiments. These results support a mechanism for
      the self-regulation of retinoblastoma expression, and point to the need to
      establish the appropriate dose of cyclin-dependent kinase inhibitors as
      antiproliferative agents in anticancer treatments.

PMID- 14653809
TI  - Perturbation of folding and reassociation of lactate dehydrogenase by proline and
      trimethylamine oxide.
AB  - Investigations of protein-solute interactions typically show that osmolytes favor
      native conformations. In this study, the effects of representative compatible and
      counteracting osmolytes on the reactivation of lactate dehydrogenase from two
      different conformational states were explored. Contrary to expectations, proline
      and trimethylamine oxide inhibited both the initial time course and the extent of
      reactivation of lactate dehydrogenase from bovine heart following denaturation in
      guanidine hydrochloride, as well as following inactivation at pH 2.3.
      Reactivation of acid-dissociated porcine heart lactate dehydrogenase was
      inhibited by both proline and trimethylamine oxide (2 M). In all instances,
      trimethylamine oxide was the more effective inhibitor of reactivation. Analysis
      of the catalytic properties of the reactivating enzyme provided evidence that the
      molecular species that was enzymatically active during the initial stages of
      reactivation of acid-inactivated porcine heart lactate dehydrogenase reflects a
      non-native conformation. Proline and trimethylamine oxide stabilize polypeptides
      through exclusion from the polypeptide backbone; the inhibition of
      renaturation/reassociation described here is probably due to attenuation of this
      stabilizing influence through favorable interactions of the osmolytes with
      sidechains of residues that lie at the interfaces of the monomers and dimers that
      associate to form the active tetramer. In addition, these osmolytes may stabilize
      non-native intermediates in the folding pathway. The high viscosity of solutions
      containing more than 3 m proline was a major factor in the inhibition of
      reassociation of acid-dissociated porcine heart lactate dehydrogenase as well as
      other viscosity-dependent transformations that may occur during reactivation
      following unfolding in guanidine hydrochloride.

PMID- 14653810
TI  - Dynamic reorganization of the motor domain of myosin subfragment 1 in different
      nucleotide states.
AB  - Atomic models of the myosin motor domain with different bound nucleotides have
      revealed the open and closed conformations of the switch 2 element [Geeves, M.A.
      & Holmes, K.C. (1999) Annu. Rev. Biochem.68, 687-728]. The two conformations are
      in dynamic equilibrium, which is controlled by the bound nucleotide. In the
      present work we attempted to characterize the flexibility of the motor domain in
      the open and closed conformations in rabbit skeletal myosin subfragment 1. Three
      residues (Ser181, Lys553 and Cys707) were labelled with fluorophores and the
      probes identified three fluorescence resonance energy transfer pairs. The effect
      of ADP, ADP.BeFx, ADP.AlF4- and ADP.Vi on the conformation of the motor domain
      was shown by applying temperature-dependent fluorescence resonance energy
      transfer methods. The 50 kDa lower domain was found to maintain substantial
      rigidity in both the open and closed conformations to provide the structural
      basis of the interaction of myosin with actin. The flexibility of the 50 kDa
      upper domain was high in the open conformation and further increased in the
      closed conformation. The converter region of subfragment 1 became more rigid
      during the open-to-closed transition, the conformational change of which can
      provide the mechanical basis of the energy transduction from the nucleotide
      binding pocket to the light-chain-binding domain.

PMID- 14653811
TI  - Solution structure and stability of the full-length excisionase from
      bacteriophage HK022.
AB  - Heteronuclear high-resolution NMR spectroscopy was employed to determine the
      solution structure of the excisionase protein (Xis) from the lambda-like
      bacteriophage HK022 and to study its sequence-specific DNA interaction. As wild
      type Xis was previously characterized as a generally unstable protein, a
      biologically active HK022 Xis mutant with a single amino acid substitution Cys28-
      >Ser was used in this work. This substitution has been shown to diminish the
      irreversibility of Xis denaturation and subsequent degradation, but does not
      affect the structural or thermodynamic properties of the protein, as evidenced by
      NMR and differential scanning calorimetry. The solution structure of HK022 Xis
      forms a compact, highly ordered protein core with two well-defined alpha-helices
      (residues 5-11 and 18-27) and five beta-strands (residues 2-4, 30-31, 35-36, 41
      44 and 48-49). These data correlate well with 1H2O-2H2O exchange experiments and
      imply a different organization of the HK022 Xis secondary structure elements in
      comparison with the previously determined structure of the bacteriophage lambda
      excisionase. Superposition of both Xis structures indicates a better
      correspondence of the full-length HK022 Xis to the typical 'winged-helix' DNA
      binding motif, as found, for example, in the DNA-binding domain of the Mu-phage
      repressor. Residues 51-72, which were not resolved in the lambda Xis, do not show
      any regular structure in HK022 Xis and thus appear to be completely disordered in
      solution. The resonance assignments have shown, however, that an unusual
      connectivity exists between residues Asn66 and Gly67 owing to asparagine
      isoaspartyl isomerization. Such an isomerization has been previously observed and
      characterized only in eukaryotic proteins.

PMID- 14653812
TI  - Photodynamic treatment and H2O2-induced oxidative stress result in different
      patterns of cellular protein oxidation.
AB  - Photodynamic treatment (PDT) is an emerging therapeutic procedure for the
      management of cancer, based on the use of photosensitizers, compounds that
      generate highly reactive oxygen species (ROS) on irradiation with visible light.
      The ROS generated may oxidize a variety of biomolecules within the cell, loaded
      with a photosensitizer. The high reactivity of these ROS restricts their radius
      of action to 5-20 nm from the site of their generation. We studied oxidation of
      intracellular proteins during PDT using the ROS-sensitive probe acetyl-tyramine
      fluorescein (acetylTyr-Fluo). This probe labels cellular proteins, which become
      oxidized at tyrosine residues under the conditions of oxidative stress in a
      reaction similar to dityrosine formation. The fluorescein-labeled proteins can be
      visualized after gel electrophoresis and subsequent Western blotting using the
      antibody against fluorescein. We found that PDT of rat or human fibroblasts,
      loaded with the photosensitizer Hypocrellin A, resulted in labeling of a set of
      intracellular proteins that was different from that observed on treatment of the
      cells with H2O2. This difference in labeling patterns was confirmed by 2D
      electrophoresis, showing that a limited, yet distinctly different, set of
      proteins is oxidized under either condition of oxidative stress. By matching the
      Western blot with the silver-stained protein map, we infer that alpha-tubulin and
      beta-tubulin are targets of PDT-induced protein oxidation. H2O2 treatment
      resulted in labeling of endoplasmic reticulum proteins. Under conditions in which
      the extent of protein oxidation was comparable, PDT caused massive apoptosis,
      whereas H2O2 treatment had no effect on cell survival. This suggests that the
      oxidative stress generated by PDT with Hypocrellin A activates apoptotic
      pathways, which are insensitive to H2O2 treatment. We hypothesize that the
      pattern of protein oxidation observed with Hypocrellin A reflects the
      intracellular localization of the photosensitizer. The application of acetylTyr
      Fluo may be useful for characterizing protein targets of oxidation by PDT with
      various photosensitizers.

PMID- 14653813
TI  - The role of residues R97 and Y331 in modulating the pH optimum of an insect beta
      glycosidase of family 1.
AB  - The activity of the digestive beta-glycosidase from Spodoptera frugiperda
      (Sfbetagly50, pH optimum 6.2) depends on E399 (pKa = 4.9; catalytic nucleophile)
      and E187 (pKa = 7.5; catalytic proton donor). Homology modelling of the
      Sfbetagly50 active site confirms that R97 and Y331 form hydrogen bonds with E399.
      Site-directed mutagenesis showed that the substitution of R97 by methionine or
      lysine increased the E399 pKa by 0.6 or 0.8 units, respectively, shifting the pH
      optima of these mutants to 6.5. The substitution of Y331 by phenylalanine
      increased the pKa of E399 and E187 by 0.7 and 1.6 units, respectively, and
      displaced the pH optimum to 7.0. From the observed deltapKa it was calculated
      that R97 and Y331 contribute 3.4 and 4.0 kJ.mol(-1), respectively, to
      stabilization of the charged E399, thus enabling it to be the catalytic
      nucleophile. The substitution of E187 by D decreased the pKa of residue 187 by
      0.5 units and shifted the pH optimum to 5.8, suggesting that an electrostatic
      repulsion between the deprotonated E399 and E187 may increase the pKa of E187,
      which then becomes the catalytic proton donor. In short the data showed that a
      network of noncovalent interactions among R97, Y331, E399 and E187 controls the
      Sfbetagly50 pH optimum. As those residues are conserved among the family 1 beta
      glycosidases, it is proposed here that similar interactions modulate the pH
      optimum of all family 1 beta-glycosidases.

PMID- 14653814
TI  - Salicylic acid and the hypersensitive response initiate distinct signal
      transduction pathways in tobacco that converge on the as-1-like element of the PR
      1a promoter.
AB  - Tobacco pathogenesis-related protein 1a (PR-1a) is induced in plants during the
      hypersensitive response (HR) after exposure of plants to salicylic acid (SA) and
      by developmental cues. Gene activation by these diverse stimuli is mediated via
      an as-1-like element in the PR-1a upstream region. To further analyze the
      significance of this cis-acting sequence, an authentic as-1 element from the
      cauliflower mosaic virus 35S RNA promoter was inserted into the PR-1a promoter in
      place of the as-1-like motif. Reporter gene analysis in transgenic tobacco plants
      demonstrated that as-1 can functionally replace the as-1-like element in the PR
      1a promoter in response to all stimuli. However, reporter gene induction from the
      as-1 carrying promoter was enhanced in response to SA compared to the wild-type
      promoter, and the ratio of reporter gene activities in SA treated leaf tissue to
      tissue exhibiting the HR increased with the as-1 promoter construct. Our findings
      support a model where PR-1a gene expression relies on at least two distinct
      signal transduction pathways initiated by SA and by a yet unknown signal produced
      during the HR, that promote different, albeit related, transcription complexes on
      the PR-1a as-1-like element. Analysis of PR-1 proteins in plants expressing
      salicylate hydroxylase yielded additional evidence that an HR dependent pathway
      leads to high level PR-1 gene induction in tobacco.

PMID- 14653815
TI  - Role of conformational flexibility for enzymatic activity in NADH oxidase from
      Thermus thermophilus.
AB  - NADH oxidase from Thermus thermophilus is a homodimer with an unknown
      physiological function. As is typical for an enzyme isolated from a thermophile,
      the catalytic rate, kcat, is low at low temperatures and increases with
      temperature, achieving an optimum at the physiological temperature of the
      organism, i.e. at approximately 70 degrees C for T. thermophilus. At low
      temperatures, the kcat of several enzymes from thermophilic and mesophilic
      organisms can be increased by chaotropic agents. The catalytic rate of NADH
      oxidase increases in the presence of urea. At concentrations of 1.0-1.3 m urea it
      reaches 250% of the activity in the absence of urea, at 20 degrees C. At higher
      urea concentrations the enzyme activity is inhibited. The urea-dependent activity
      changes correlate with changes in the fluorescence intensity of Trp47, which is
      located in the active site of the enzyme. Both fluorescence and circular
      dichroism measurements indicate that the activation by chaotropic agents involves
      local environmental changes accompanied by increased dynamics in the active site
      of the enzyme. This is not related to the global structure of NADH oxidase. The
      presence of an aromatic amino acid interacting with the flavin cofactor is common
      to numerous flavin-dependent oxidases. A comparison of the crystal structure with
      the activation thermodynamic parameters, deltaH* and TdeltaS*, obtained from the
      temperature dependence of kcat, suggests that Trp47 interacts with a water
      molecule and the isoalloxazine flavin ring. The present investigation suggests a
      model that explains the role of the homodimeric structure of NADH oxidase.

PMID- 14653816
TI  - Regulation of maize lysine metabolism and endosperm protein synthesis by opaque
      and floury mutations.
AB  - The capacity of two maize opaque endosperm mutants (o1 and o2) and two floury
      (fl1 and fl2) to accumulate lysine in the seed in relation to their wild type
      counterparts Oh43+ was examined. The highest total lysine content was 3.78% in
      the o2 mutant and the lowest 1.87% in fl1, as compared with the wild type
      (1.49%). For soluble lysine, o2 exhibited over a 700% increase, whilst for fl3 a
      28% decrease was encountered, as compared with the wild type. In order to
      understand the mechanisms causing these large variations in both total and
      soluble lysine content, a quantitative and qualitative study of the N
      constituents of the endosperm has been carried out and data obtained for the
      total protein, nonprotein N, soluble amino acids, albumins/globulins, zeins and
      glutelins present in the seed of the mutants. Following two-dimensional PAGE
      separation, a total of 35 different forms of zein polypeptides were detected and
      considerable differences were noted between the five different lines. In
      addition, two enzymes of the aspartate biosynthetic pathway, aspartate kinase and
      homoserine dehydrogenase were analyzed with respect to feedback inhibition by
      lysine and threonine. The activities of the enzymes lysine 2-oxoglutate reductase
      and saccharopine dehydrogenase, both involved in lysine degradation in the maize
      endosperm were also determined and shown to be reduced several fold with the
      introduction of the o2, fl1 and fl2 mutations in the Oh43+ inbred line, whereas
      wild-type activity levels were verified in the Oh43o1 mutant.

PMID- 14653817
TI  - The astacin protein family in Caenorhabditis elegans.
AB  - In the nematode Caenorhabditis elegans, 40 genes code for astacin-like proteins
      (nematode astacins, NAS). The astacins are metalloproteases present in bacteria,
      invertebrates and vertebrates and serve a variety of physiological functions like
      digestion, hatching, peptide processing, morphogenesis and pattern formation.
      With the exception of one distorted pseudogene, all the other C. elegans astacins
      are expressed and are evidently functional. For 13 genes we found splicing
      patterns differing from the Genefinder predictions in WormBase, sometimes
      markedly. The GFP expression pattern for NAS-4 shows a specific localization in
      anterior pharynx cells and in the whole digestive tract (as the secreted form).
      In contrast, NAS-7 is found in the head of adult hermaphrodites, but not in
      pharynx cells or in the lumen of the digestive tract. In embryos, NAS-7
      fluorescence becomes detectable just before hatching. In C. elegans astacins,
      three basic structural and functional moieties can be discerned: a prepro
      portion, the central catalytic chain and long C-terminal extensions with
      presumably regulatory functions. Within the regulatory moiety, EFG-like, CUB,
      SXC, and TSP-1 domains can be distinguished. Based on structural differences of
      the regulatory unit we established six NAS subgroups, which seemingly represented
      different functional and evolutionary clusters. This pattern deduced exclusively
      from the domain arrangement in the regulatory moiety is perfectly reflected in an
      evolutionary tree constructed solely from amino acid sequence information of the
      catalytic chain. Related catalytic chains tend to have related regulatory
      extensions. The notable gene, NAS-39 shows a striking resemblance to human BMP-1
      and the tolloids.

PMID- 14653818
TI  - Inhibitors of protein phosphatase 1 and 2A decrease the level of tubulin
      carboxypeptidase activity associated with microtubules.
AB  - The association of tubulin carboxypeptidase with microtubules may be involved in
      the determination of the tyrosination state of the microtubules, i.e. their
      proportion of tyrosinated vs. nontyrosinated tubulin. We investigated the role of
      protein phosphatases in the association of carboxypeptidase with microtubules in
      COS cells. Okadaic acid and other PP1/PP2A inhibitors, when added to culture
      medium before isolation of the cytoskeletal fraction, produced near depletion of
      the carboxypeptidase activity associated with microtubules. Isolation of the
      native assembled and nonassembled tubulin fractions from cells treated and not
      treated with okadaic acid, and subsequent in vitro assay of the carboxypeptidase
      activity, revealed that the enzyme was dissociated from microtubules by okadaic
      acid treatment and recovered in the soluble fraction. There was no effect by nor
      okadaone (an inactive okadaic acid analogue) or inhibitors of PP2B and of
      tyrosine phosphatases which do not affect PP1/PP2A activity. When tested in an in
      vitro system, okadaic acid neither dissociated the enzyme from microtubules nor
      inactivated it. In living cells, prior stabilization of microtubules with taxol
      prevented the dissociation of carboxypeptidase by okadaic acid indicating that
      dynamic microtubules are needed for okadaic acid to exert its effect. On the
      other hand, stabilization of microtubules subsequent to okadaic acid treatment
      did not reverse the dissociating effect of okadaic acid. These results suggest
      that dephosphorylation (and presumably also phosphorylation) of the
      carboxypeptidase or an intermediate compound occurs while it is not associated
      with microtubules, and that the phosphate content determines whether or not the
      carboxypeptidase is able to associate with microtubules.

PMID- 14653819
TI  - Functional assembly of thylakoid deltapH-dependent/Tat protein transport pathway
      components in vitro.
AB  - Assembly of the components of the thylakoid deltapH-dependent/Tat protein
      transport machinery was analyzed in vitro. Upon incubation with intact
      chloroplasts, precursors to all three components, Hcf106, cpTatC and Tha4, were
      imported into the organelle and assembled into characteristic endogenous
      complexes. In particular, all of the imported cpTatC and approximately two-thirds
      of the imported Hcf106 functionally assembled into 700 kDa complexes capable of
      binding Tat pathway precursor proteins. The amounts assembled into thylakoids by
      this procedure were moderate. However, physiological quantities of mature forms
      of Tha4 and Hcf106 were integrated into isolated thylakoids and a significant
      percentage of the Hcf106 so integrated was assembled into the 700 kDa complex.
      Interestingly, a mutant form of Hcf106 in which an invariant transmembrane
      glutamate was changed to glutamine integrated into the membrane but did not
      assemble into the receptor complex. Analysis of energy and known pathway
      component requirements indicated that Hcf106 and Tha4 integrate by an unassisted
      or 'spontaneous' mechanism. The functionality of in vitro integrated Tha4 was
      verified by its ability to restore transport to thylakoid membranes from the
      maize tha4 mutant, which lacks the Tha4 protein. Development of this functional
      in vitro assembly assay will facilitate structure-function studies of the
      thylakoid Tat pathway translocation machinery.

PMID- 14653820
TI  - Cytosol-mitochondria transfer of reducing equivalents by a lactate shuttle in
      heterotrophic Euglena.
AB  - To assess the expression and physiological role of the mitochondrial NAD(+)
      independent lactate dehydrogenase (iLDH) in Euglena gracilis, cells were grown
      with different carbon sources, and the d- and l-iLDH activities and several key
      metabolic intermediates were examined. iLDH activity was significant throughout
      the growth period, increasing by three- to fourfold from latency to the
      stationary phase. Intracellular levels of D- and L-lactate were high (5-40 mm)
      from the start of the culture and increased (20-80 mm) when the stationary phase
      was entered. All external carbon sources were actively consumed, reaching a
      minimum upon entering the stationary phase, when degradation of paramylon
      started. The level of ATP was essentially unchanged under all experimental
      conditions. Oxalate, an inhibitor of iLDH, strongly inhibited oligomycin
      sensitive respiration and growth, whereas rotenone, an inhibitor of respiratory
      complex I, only slightly affected these parameters in lactate-grown cells.
      Isolated mitochondria exhibited external NADH-supported respiration, which was
      sensitive to rotenone and flavone, and an inability to oxidize pyruvate. Addition
      of cytosol, NADH and pyruvate to mitochondria incubated with rotenone and flavone
      prompted significant O2 uptake, which was blocked by oxalate. The data suggested
      that iLDH expression in Euglena is independent of substrate availability and that
      iLDHs play a key role in the transfer of reducing equivalents from the cytosol to
      the respiratory chain (lactate shuttle).

PMID- 14653821
TI  - De novo RNA synthesis by a recombinant classical swine fever virus RNA-dependent
      RNA polymerase.
AB  - Classical swine fever virus nonstructural protein 5B (NS5B) encodes an RNA
      dependent RNA polymerase, a key enzyme of the viral replication complex. To
      better understand the initiation of viral RNA synthesis and to establish an in
      vitro replication system, a recombinant NS5B protein, lacking the C-terminal 24
      amino acid hydrophobic domain, was expressed in Escherichia coli. The truncated
      fusion protein (NS5Bdelta24) was purified on a Ni-chelating HisTrap affinity
      column and demonstrated to initiate either plus- or minus-strand viral RNA
      synthesis de novo in a primer-independent manner but not by terminal nucleotidyle
      transferase activity. De novo RNA synthesis represented the preferred mechanism
      for initiation of classical swine fever virus RNA synthesis by RNA-dependent RNA
      polymerase in vitro. Both Mg2+ and Mn2+ supported de novo initiation, however,
      RNA synthesis was more efficient in the presence of Mn2+ than in the presence of
      Mg2+. De novo initiation of RNA synthesis was stimulated by preincubation with
      0.5 mm GTP, and a 3'-terminal cytidylate on the viral RNA template was preferred
      for de novo initiation. Furthermore, the purified protein was also shown, by
      North-Western blot analysis, to specifically interact with the 3'-end of both
      plus- and minus-strand viral RNA templates.

PMID- 14653823
TI  - Development of a baculovirus-based fluorescence resonance energy transfer assay
      for measuring protein-protein interaction.
AB  - A new baculovirus-based fluorescence resonance energy transfer (Bv-FRET) assay
      for measuring multimerization of cell surface molecules in living cells is
      described. It has been demonstrated that gonadotropin-releasing hormone receptor
      (GnRH-R) was capable of forming oligomeric complexes in the plasma membrane under
      normal physiological conditions. The mouse gonadotropin-releasing hormone
      receptor GnRH-R was used to evaluate the efficiency and potential applications of
      this assay. Two chimeric constructs of GnRH-R were made, one with green
      fluorescent protein as a donor fluorophore and the other with enhanced yellow
      fluorescent protein as an acceptor fluorophore. These chimeric constructs were
      coexpressed in an insect cell line (BTI Tn5 B1-4) using recombinant
      baculoviruses. Energy transfer occurred from the excited donor to the acceptor
      when they were in close proximity. The association of GnRH-R was demonstrated
      through FRET and the fluorescence observed using a Leica TSC-SPII confocal
      microscope. FRET was enhanced by the addition of a GnRH agonist but not by an
      antagonist. The Bv-FRET assay constitutes a highly efficient, reliable and
      convenient method for measuring protein-protein interaction as the baculovirus
      expression system is superior to other transfection-based methods. Additionally,
      the same insect cell line can be used routinely for expressing any recombinant
      proteins of interest, allowing various combinations of molecules to be tested in
      a rapid fashion for protein-protein interactions. The assay is a valuable tool
      not only for the screening of new molecules that interact with known bait
      molecules, but also for confirming interactions between other known molecules.

PMID- 14653822
TI  - A 49 kDa microtubule cross-linking protein from Artemia franciscana is a coenzyme
      A-transferase.
AB  - Embryos and larvae of the brine shrimp, Artemia franciscana, were shown
      previously to possess a protein, now termed p49, which cross-links microtubules
      in vitro. Molecular characteristics of p49 were described, but the protein's
      identity and its role in the cell were not determined. Degenerate oligonucleotide
      primers designed on the basis of peptide sequence obtained by Edman degradation
      during this study were used to generate p49 cDNAs by RT-PCR and these were cloned
      and sequenced. Comparison with archived sequences revealed that the deduced amino
      acid sequence of p49 resembled the Drosophila gene product CG7920, as well as
      related proteins encoded in the genomes of Anopheles and Caenorhabditis. Similar
      proteins exist in several bacteria but no evident homologues were found in
      vertebrates and plants, and only very distant homologues resided in yeast. When
      evolutionary relationships were compared, p49 and the homologues from Drosophila,
      Anopheles and Caenorhabditis formed a distinct subcluster within phylogenetic
      trees. Additionally, the predicted secondary structures of p49, 4-hydroxybutyrate
      CoA-transferase from Clostridium aminobutyricum and glutaconate CoA-transferase
      from Acidaminococcus fermentans were similar and the enzymes may possess related
      catalytic mechanisms. The purified Artemia protein exhibited 4-hydroxybutyrate
      CoA-transferase activity, thereby establishing p49 as the first crustacean CoA
      transferase to be characterized. Probing of Western blots with an antibody
      against p49 revealed a cross-reactive protein in Drosophila that associated with
      microtubules, but to a lesser extent than did p49 from Artemia.

PMID- 14653824
TI  - DNA sequence specificity of triplex-binding ligands.
AB  - We have examined the ability of naphthylquinoline, a 2,7-disubstituted
      anthraquinone and BePI, a benzo[e]pyridoindole derivative, to stabilize parallel
      DNA triplexes of different base composition. Fluorescence melting studies, with
      both inter- and intramolecular triplexes, show that all three ligands stabilize
      triplexes that contain blocks of TAT triplets. Naphthylquinoline has no effect on
      triplexes formed with third strands composed of (TC)n or (CCT)n, but stabilizes
      triplexes that contain (TTC)n. In contrast, BePI slightly destabilizes the
      triplexes that are formed at (TC)n (CCT)n and (TTC)n. 2,7-Anthraquinone
      stabilizes (TC)n (CCT)n and (TTC)n, although it has the greatest effect on the
      latter. DNase I footprinting studies confirm that triplexes formed with (CCT)n
      are stabilized by the 2,7-disubstituted amidoanthraquinone but not by
      naphthylquinoline. Both ligands stabilize the triplex formed with (CCTT)n and
      neither affects the complex with (CT)n. We suggest that BePI and
      naphthylquinoline can only bind between adjacent TAT triplets, while the
      anthraquinone has a broader sequence of selectivity. These differences may be
      attributed to the presence (naphthylquinoline and BePI) or absence
      (anthraquinone) of a positive charge on the aromatic portion of the ligand, which
      prevents intercalation adjacent to C+GC triplets. The most stable structures are
      formed when the stacked rings (bases or ligand) alternate between charged and
      uncharged species. Triplexes containing alternating C+GC and TAT triplets are not
      stabilized by ligands as they would interrupt the alternating pattern of charged
      and uncharged residues.

PMID- 14653825
TI  - Review article: chemotherapy for pancreatic cancer.
AB  - Pancreatic cancer is a common, highly lethal disease that is rising in incidence.
      Chemotherapy based on 5-fluorouracil (5-FU) has been shown to prolong survival in
      advanced pancreatic cancer. Gemcitabine improves major symptoms and survival
      outcomes compared with bolus 5-FU. Many novel small molecules are being widely
      and actively researched. These compounds are based on classical mechanisms of
      action as well as biological therapies targeting novel cellular survival
      pathways, and include fluoropyrimidines, nucleoside cytidine analogues, platinum
      analogues, topoisomerase-inhibitors, antimicrotubule agents, proteasome
      inhibitors, vitamin D analogues, arachidonic acid pathway inhibitors, histone
      deacytylator inhibitors, farnesyltransferase inhibitors and epidermal growth
      factor receptor therapies. Adjuvant chemotherapy has also demonstrated the best
      survival outcomes following resection compared to other adjuvant or neo-adjuvant
      strategies such as radiation-based treatments. These benefits are superimposed on
      the dramatic increase in resectability rates and reduction in post-operative
      mortality achieved by centralisation of treatment in high-volume speciality
      centres. Newer 'small-molecule' drugs as well as the latest 'large-molecule'
      biological agents hold considerable promise for the future. Real advances are
      anticipated over the next five years but are dependent on large randomised
      controlled trials for success.

PMID- 14653826
TI  - Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis
      patients.
AB  - BACKGROUND: The efficacy of interferon monotherapy in dialysis patients with
      chronic hepatitis C remains unclear, although a number of small clinical trials
      have been published addressing this issue. METHODS AND AIMS: We evaluated the
      efficacy and safety of initial interferon monotherapy in dialysis patients with
      chronic hepatitis C by performing a systematic review of the literature with a
      meta-analysis of clinical trials. The primary outcome was sustained virological
      response (as a measure of efficacy); the secondary outcome was drop-out rate (as
      a measure of tolerability). We used the random effects model of Der Simonian and
      Laird, with heterogeneity and sensitivity analyses. RESULTS: We have identified
      14 clinical trials (269 unique patients); two were controlled studies. The mean
      overall estimate for sustained virological response (SVR) and drop-out rate was
      37%[95% confidence interval (CI) 28-48] and 17% (95% CI 10-28), respectively. The
      most frequent side-effects requiring interruption of treatment were flu-like
      symptoms (17%), neurological (21%) and gastrointestinal (18%). The overall
      weighted estimate for SVR in patients with hepatitis C virus genotype 1 was 30.6%
      (95% CI 20.9-48). In the sub-group of clinical trials (n = 5) with standard
      interferon administration (3 million units [MUI] thrice weekly, subcutaneous
      route, 24-week treatment), the overall mean estimate of SVR was 39% (95% CI 25
      56). The studies were heterogeneous with regard to SVR and drop-out rate.
      CONCLUSIONS: Tolerance to initial interferon monotherapy was lower in dialysis
      than nonuremic patients with chronic hepatitis C. However, more than one-third of
      haemodialysis patients with chronic hepatitis C have been successfully treated
      with interferon. Longer duration of interferon monotherapy does not appear to
      have a beneficial effect on the response rate. Further studies are warranted to
      define the optimal anti-viral regimen for chronic hepatitis C in dialysis
      population.

PMID- 14653827
TI  - Assessment of oesophageal motor function in patients with dysphagia or chest pain
      - the Clinical Outcomes Research Initiative experience.
AB  - BACKGROUND: Available prospectively acquired data on the distribution of
      oesophageal motor abnormalities in patients being evaluated for non-cardiac chest
      pain and/or dysphagia are relatively scarce. AIM: To evaluate the distribution of
      oesophageal motor abnormalities in patients with dysphagia, non-cardiac chest
      pain or both using the national Clinical Outcomes Research Initiative (CORI)
      database. METHODS: The CORI oesophageal motility database originates from 19
      community, university and VA medical centres. Data were collected using a
      computerized motility report-generating program, combined with the CORI module.
      Data from each site were encrypted and sent to the CORI National Repository for
      analysis. The database includes the assessment of the lower and upper oesophageal
      sphincter function and the motor activity of the oesophageal body. RESULTS: Five
      hundred and eighty-seven consecutive patients who underwent motility studies
      between 1998 and 2001 were included in the CORI database and analysed for this
      report. Four hundred and three patients (69%) had dysphagia as their primary
      indicator for the examination, 140 patients (24%) had non-cardiac chest pain and
      44 patients (7%) had both dysphagia and non-cardiac chest pain. In all three
      groups, a normal motility study was the most frequent finding (dysphagia, 53%;
      chest pain, 70%; both, 55%). The most common motility abnormality in the group
      with non-cardiac chest pain was a hypotensive lower oesophageal sphincter (61%).
      Nutcracker oesophagus and non-specific oesophageal motility disorders were each
      diagnosed in only 10% of patients with non-cardiac chest pain. In patients with
      dysphagia, ineffective peristalsis was the most common oesophageal dysmotility
      (27%), followed by achalasia and non-specific oesophageal motility disorders (18%
      and 14%, respectively). Achalasia and non-specific oesophageal motility disorders
      were the most common oesophageal motility abnormalities in patients with both
      chest pain and dysphagia (35% and 25%, respectively). CONCLUSIONS: The most
      common oesophageal motility abnormality in patients with non-cardiac chest pain
      is a hypotensive lower oesophageal sphincter; nutcracker oesophagus and non
      specific oesophageal motility disorders are relatively uncommon; the most common
      oesophageal motility abnormality in patients with dysphagia is ineffective
      peristalsis and, for those with both dysphagia and non-cardiac chest pain, it is
      achalasia.

PMID- 14653828
TI  - Different patterns of oesophageal acid exposure distinguish complicated reflux
      disease from either erosive reflux oesophagitis or non-erosive reflux disease.
AB  - BACKGROUND: The reason why less than one-half of patients with gastro-oesophageal
      reflux disease develop complicated reflux disease (ulcerative oesophagitis,
      oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis
      is not fully understood. Supine nocturnal oesophageal acid reflux is considered
      to be critically involved in this phenomenon, but reliable data are lacking. AIM:
      To clarify whether high levels of supine nocturnal oesophageal acid exposure are
      associated with complicated reflux disease. METHODS: Ambulatory 24-h oesophageal
      pH monitoring was performed in 220 patients with gastro-oesophageal reflux
      disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis
      and 88 with non-erosive reflux disease). The total, supine nocturnal and upright
      diurnal percentage acid reflux times were calculated. RESULTS: The total
      percentage acid reflux time was significantly greater in complicated reflux
      disease than in either erosive reflux oesophagitis (P = 0.024) or non-erosive
      reflux disease (P = 0.000). These differences were entirely due to a greater
      supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000,
      respectively), whereas no difference was observed in the upright diurnal
      percentage acid reflux time. CONCLUSIONS: Complicated reflux disease is
      characterized by high levels of supine nocturnal percentage acid reflux time.
      Prospective studies would be appropriate to clarify whether the normalization of
      this parameter is relevant to the effective management of this subset of patients
      with gastro-oesophageal reflux disease.

PMID- 14653829
TI  - Efficacy of artichoke leaf extract in the treatment of patients with functional
      dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial.
AB  - BACKGROUND: This study aimed to assess the efficacy of artichoke leaf extract
      (ALE) in the treatment of patients with functional dyspepsia (FD). METHODS: In a
      double-blind, randomized controlled trial (RCT), 247 patients with functional
      dyspepsia were recruited and treated with either a commercial ALE preparation (2
      x 320 mg plant extract t.d.s.) or a placebo. The primary efficacy variable was
      the sum score of the patient's weekly rating of the overall change in dyspeptic
      symptoms (four-point scale). Secondary variables were the scores of each
      dyspeptic symptom and the quality of life (QOL) as assessed by the Nepean
      Dyspepsia Index (NDI). RESULTS: Two hundred and forty-seven patients were
      enrolled, and data from 244 patients (129 active treatment, 115 placebo) were
      suitable for inclusion in the statistical analysis (intention-to-treat). The
      overall symptom improvement over the 6 weeks of treatment was significantly
      greater with ALE than with the placebo (8.3 +/- 4.6, vs. 6.7 +/- 4.8, P < 0.01).
      Similarly, patients treated with ALE showed significantly greater improvement in
      the global quality-of-life scores (NDI) compared with the placebo-treated
      patients (- 41.1 +/- 47.6 vs. - 24.8 +/- 35.6, P < 0.01). CONCLUSION: The ALE
      preparation tested was significantly better than the placebo in alleviating
      symptoms and improving the disease-specific quality of life in patients with
      functional dyspepsia.

PMID- 14653830
TI  - Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn's
      disease.
AB  - BACKGROUND: Small bowel bacterial overgrowth is common in Crohn's disease but its
      treatment is not clearly defined. Metronidazole and ciprofloxacin are effective
      antibiotics in active Crohn's disease. AIM: To investigate the efficacy of
      metronidazole and ciprofloxacin in the treatment of bacterial overgrowth in
      patients with Crohn's disease. PATIENTS AND METHODS: We performed the lactulose
      breath test in 145 consecutive patients affected by Crohn's disease. Patients
      positive to the lactulose breath test underwent a glucose breath test to confirm
      the overgrowth. These patients were randomized in two treatment groups:
      metronidazole 250 mg t.d.s. (Group A) and ciprofloxacin 500 mg b.d. (Group B),
      both orally for 10 days. The glucose breath test was repeated at the end of
      treatment. The clinical outcome after therapy was also recorded. RESULTS:
      Bacterial overgrowth was present in 29 patients (20%). Breath test normalization
      occurred in 13 out of 15 patients treated by metronidazole and in all 14 patients
      treated by ciprofloxacin (P = ns). In both groups antibiotic treatment induced an
      improvement of intestinal symptoms: bloating (Group A 85% and Group B 83%), stool
      softness (44% and 50%), and abdominal pain (50% and 43%). CONCLUSIONS: Small
      bowel bacterial overgrowth is a frequent condition in Crohn's disease which can
      be effectively treated by metronidazole or ciprofloxacin.

PMID- 14653831
TI  - Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's
      disease.
AB  - BACKGROUND: Antibiotics and thiopurines have been employed in the management of
      fistulizing Crohn's disease, although evidence of their efficacy is rare. AIM: To
      evaluate, in a prospective, open-label study, the influence of antibiotics and
      azathioprine on the clinical outcome of perianal fistulas in patients with
      Crohn's disease. METHODS: Fifty-two patients entered the study, starting with an
      8-week regimen of ciprofloxacin (500-1000 mg/day) and/or metronidazole (1000-1500
      mg/day). Seventeen patients had already received daily azathioprine (2-2.5 mg/kg)
      at enrollment, whereas in 14 patients azathioprine was initiated after 8 weeks of
      antibiotic treatment. Outcome was evaluated by Fistula Drainage Assessment and
      the Perianal Disease Activity Index at weeks 8 and 20. RESULTS: Overall, 26
      patients (50%) responded to antibiotic treatment, with complete healing in 25% of
      patients at week 8. The Perianal Disease Activity Index decreased significantly
      from 8.4 +/- 2.9 to 6.0 +/- 4.0 (P < 0.0001). At week 20, the outcome was
      assessed in 49 patients (94%), 29 of whom (59%) had received azathioprine.
      Response was noted in 17 of the 49 patients (35%), with complete healing in nine
      patients (18%). Patients who received azathioprine were more likely to achieve a
      response (48%) than those without immunosuppression (15%) (P = 0.03). The
      Perianal Disease Activity Index was closely associated with treatment response
      and perianal disease activity. CONCLUSION: Antibiotics are useful to induce a
      short-term response in perianal Crohn's disease, and may provide a bridging
      strategy to azathioprine, which seems to be essential for the maintenance of
      fistula improvement.

PMID- 14653832
TI  - A randomized controlled trial of calcium with vitamin D, alone or in combination
      with intravenous pamidronate, for the treatment of low bone mineral density
      associated with Crohn's disease.
AB  - BACKGROUND: Osteoporosis is a common complication of Crohn's disease. AIM: To
      study the effect on the bone mineral density of a bisphosphonate (pamidronate)
      given intravenously, in combination with oral calcium and vitamin D supplements,
      compared with oral calcium and vitamin D supplements alone. METHODS: Seventy-four
      patients with Crohn's disease and low bone mineral density at the lumbar spine
      and/or hip were randomized to receive either a daily dose of 500 mg of calcium
      with 400 IU of vitamin D alone or in combination with four three-monthly
      infusions of 30 mg of intravenous pamidronate over the course of 12 months. The
      main outcome measure was the change in bone mineral density at the lumbar spine
      and hip, measured by dual X-ray absorptiometry, at baseline and 12 months.
      RESULTS: Both groups gained bone mineral density at the lumbar spine and hip
      after 12 months. There were significant (P < 0.05) changes in the pamidronate
      group, with gains of + 2.6%[95% confidence interval (CI), 1.4-3.0] at the spine
      and + 1.6% (95% CI, 0.6-2.5) at the hip, compared with gains of + 1.6% (95% CI, -
      0.1-3.2) and + 0.9% (95% CI, - 0.4-2.1) at the spine and hip, respectively, in
      the group taking vitamin D and calcium supplements alone. CONCLUSIONS: In
      patients with Crohn's disease and low bone mineral density, intravenous
      pamidronate significantly increases the bone mineral density at the lumbar spine
      and hip.

PMID- 14653833
TI  - Nutcracker oesophagus: a double-blind, placebo-controlled, cross-over study of
      the effects of lansoprazole.
AB  - BACKGROUND: Nutcracker oesophagus is characterized by high-amplitude oesophageal
      contractions. Recent data have shown a high prevalence of gastro-oesophageal acid
      reflux in patients with nutcracker oesophagus and, in open-label trials, patients
      seemed to benefit from acid suppression. Therefore, it has been suggested that
      non-cardiac chest pain in patients with nutcracker oesophagus may be related to
      reflux rather than to the motor abnormality itself. AIMS: To investigate the
      effect of intensive acid-suppressive treatment on chest pain in patients with
      nutcracker oesophagus. METHODS: Nineteen patients with nutcracker oesophagus
      received lansoprazole or placebo in a double-blind, randomized, cross-over study.
      RESULTS: Significant reductions in pain intensity (P < 0.006) and pain duration
      (P < 0.05) were registered during the study. The magnitude of symptom relief
      achieved with lansoprazole did not differ significantly from that achieved with
      placebo. The motility pattern did not change during the study. CONCLUSIONS: This
      study does not prove that acid-suppressive therapy is effective for pain relief
      in nutcracker oesophagus. As the amelioration of pain was not accompanied by any
      change in the nutcracker oesophagus pattern, it is unlikely that the high
      amplitude oesophageal contractions are the cause of pain. Thus, the possible role
      of acid in the pathophysiology of pain in nutcracker oesophagus needs further
      study.

PMID- 14653834
TI  - Adherence to proton pump inhibitors or H2-receptor antagonists during the use of
      non-steroidal anti-inflammatory drugs.
AB  - BACKGROUND: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor
      antagonists (H2RAs) prescribed as prophylaxis for NSAID-related upper
      gastrointestinal (UGI) toxicity is dependent upon patient adherence. AIM: To
      describe patient adherence to prophylactically prescribed PPIs and H2RAs in the
      clinical setting. METHODS: We conducted a retrospective observational cohort
      study using the Integrated Primary Care Information Project database. The study
      population consisted of incident non-specific NSAID users prescribed a PPI or
      H2RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were
      classified as non-adherent if < 75% of days of NSAID use were covered by one of
      these agents, and as continuing users after discontinuation of NSAID use if they
      had a renewed prescription for these agents after their last NSAID prescription.
      RESULTS: The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs,
      and 5 with both PPI and H2RA. Eighty-five percent of H2RA users and 7% of PPI
      users were prescribed these drugs at doses below the minimum
      recommended/effective dose for NSAID-associated gastroduodenal ulcer prophylaxis.
      Thirty-seven percent of patients were non-adherent. The lowest rate of non
      adherence was associated with the first NSAID prescription (9%), increasing to
      61% for patients with >/= 3 prescriptions. In a cohort of subjects who stopped
      their NSAID and were followed for up to 2 years (n = 711), there was significant
      persistent use of acid suppressive agents; 40% of patients had at least one
      additional prescription for the acid suppressive agent after stopping NSAIDs,
      and> 30% received enough drug to cover a period longer than 2 months after
      stopping their NSAID. CONCLUSIONS: The pattern of PPI and H2RA prescriptions,
      when prescribed as prophylactic strategy, does not correspond with the pattern of
      NSAID use. Physicians should consider the medical impact of non-adherence with
      dual therapies and the impact of prolonged use of GPAs on treatment cost.

PMID- 14653835
TI  - Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19
      genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2-receptor
      antagonist.
AB  - BACKGROUND: Omeprazole 10 mg is used as maintenance therapy for gastro
      oesophageal reflux disease, but previous reports have not mentioned the potency
      of its acid suppression. AIM: To evaluate the potency of acid suppression with
      omeprazole 10 mg, in relation to CYP2C19 genotypes. METHODS: Eighteen healthy
      subjects without Helicobacter pylori participated. After a 7-day regimen of
      omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2-receptor antagonist) or
      water only (baseline data), intragastric pH was measured for 24 h. RESULTS: With
      omeprazole 10 mg, greater differences were observed than 20 mg in median pH
      values and pH > 4 holding time ratios between poor metabolizers (PMs, n = 6) and
      the others [homozygous extensive metabolizers (homo-EMs, n = 6) and heterozygous
      extensive metabolizers (hetero-EMs, n = 6)]. With lafutidine 20 mg, these
      parameters were not influenced by the genotype. The potency of acid suppression
      was: omeprazole 20 mg approximately lafutidine 20 mg > omeprazole 10 mg in homo
      EMs, omeprazole 20 mg > omeprazole 10 mg approximately lafutidine 20 mg in hetero
      EMs, and omeprazole 20 mg approximately omeprazole 10 mg > lafutidine 20 mg in
      PMs. CONCLUSIONS: Omeprazole 10 mg strongly suppresses acid secretion, but
      depending on the CYP2C19 genotypes shows greater interindividual variations in
      suppression than 20 mg.

PMID- 14653836
TI  - Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire
      on a Chinese population.
AB  - BACKGROUND: Irritable bowel syndrome is a common condition seen in Western
      countries. In Asia, however, it is less known and even less studied. AIM: To
      determine the prevalence and social impact of irritable bowel syndrome as well as
      the health-seeking behaviour of irritable bowel syndrome patients in Taiwan
      METHODS: Using the modified Rome II questionnaire, a survey was carried out in a
      population receiving physical check-up (n = 2865). RESULTS: The prevalence of
      irritable bowel syndrome in Taiwan was 22.1% and 17.5% (kappa = 0.73) according
      to the Rome II and I criteria, respectively. No gender difference was found
      between subjects with and without irritable bowel syndrome symptoms. Irritable
      bowel syndrome subjects were likely to undertake an excessive number of physician
      visits (P < 0.01). Such subjects were often absent from work/school, with more
      days of absenteeism than irritable bowel syndrome-free subjects (P < 0.01). They
      also suffered obvious sleep disturbance (P < 0.01). Nearly half of the irritable
      bowel syndrome subjects were 'consulters', and they were more likely to have
      frequent physician-visits, suffer from work/school absenteeism, and endure sleep
      disturbance and bowel symptoms than irritable bowel syndrome nonconsulters (P <
      0.05). CONCLUSIONS: Irritable bowel syndrome is common in a Chinese population of
      Taiwan. Similar to irritable bowel syndrome in the West, it also involves
      significant social and medical burdens. However, in the irritable bowel syndrome
      subjects of Taiwan there is no gender difference, and more irritable bowel
      syndrome subjects will seek physician consultations, which may be due to Taiwan's
      easily accessible and affordable heath care facilities.

PMID- 14653837
TI  - Placebo treatment for anal fissure.

PMID- 14653839
TI  - Management of acute gastric variceal bleeding.

PMID- 14653840
TI  - Post-infective tropical malabsorption and irritable bowel syndrome: causality and
      mimicry?

PMID- 14653841
TI  - Retreatment of H. pylori with dual therapy using high doses of rabeprazole or
      lansoprazole can be effective.

PMID- 14653842
TI  - 13C-methacetin breath test and oxygen supply.

PMID- 14653844
TI  - Use of gene therapy in central nervous system repair.
AB  - Recent advances have increased our molecular understanding of the central nervous
      system (CNS), in both health and disease. In order to realize the clinical
      benefits of these findings, new molecular-based therapies need to be developed,
      such as CNS gene therapy. Although the field has suffered setbacks, it remains an
      attractive technology for providing new therapies in the post-genomic world. The
      development of new vectors, and their extensive application in animal models of
      CNS disease, provides evidence suggesting that gene therapy will eventually
      become an accepted clinical option. In fact, the first gene therapy clinical
      trial for Parkinson's disease has recently begun. This review discusses how gene
      therapy has been applied in animal models, and how it may be used to repair the
      damage caused by CNS diseases and trauma in human beings. Furthermore, it
      explores how such treatments may be combined with, and augment, more conventional
      therapeutic approaches.

PMID- 14653845
TI  - Epilepsy and pregnancy: lamotrigine as main drug used.
AB  - OBJECTIVES: To study the risk of teratogenicity in infants of women with
      epilepsy. MATERIAL AND METHODS: Prospective data from 1996 to 2000 comprised 147
      pregnancies. The most frequent antiepileptic drugs (AEDs) used were lamotrigine
      (LTG) 35% (n = 51), oxcarbazepine (OXC) 25% (n = 37) and valproate (VPA) 20% (n =
      30). Seventy-four per cent (n = 109) received monotherapy. Folic acid
      supplementation was taken during first trimester by 118 patients (80%). RESULTS:
      The overall risk of malformations among newborns in the AED-exposed group was
      3.1% (n = 4). Two children were born with multiple malformations (VPA
      monotherapy), two children had ventricular septal defects (one OXC monotherapy,
      and one OXC and LTG). The risk of malformations was 2.0% in women treated with
      LTG and 6.7% in women treated with VPA (NS). CONCLUSION: Despite the small number
      of cases in the study these data indicate that treatment with LTG during
      pregnancy might be relatively safe. Larger prospective studies are needed to
      obtain adequate power for statistical analysis.

PMID- 14653847
TI  - Haemodynamic and metabolic disturbances in the acute stage of subarachnoid
      haemorrhage demonstrated by PET.
AB  - OBJECTIVE: To investigate the occurrence of early haemodynamic and metabolic
      changes in the acute stage of subarachnoid haemorrhage (SAH). MATERIAL AND
      METHODS: Eleven SAH patients were studied. Regional cerebral blood flow (CBF),
      cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction ratio (OER) were
      measured with positron emission tomography (PET) 22-53 h after haemorrhage,
      utilizing 15O-labelled water bolus and the 15O-inhalation technique. Ten volumes
      of interest (VOIs) representing vascular territories were outlined in each
      patient according to a standardized procedure. The occurrence of irreversible
      ischaemia, penumbra, oligaemia, hyperperfusion and normal haemodynamics according
      to PET criteria was investigated. These pathophysiological categories were
      related to final tissue outcome as determined by follow-up computed tomography
      (CT). RESULTS: All five tissue subtypes were represented in the vascular region
      VOIs; oligaemia was the predominant pathophysiological pattern. When global
      changes were analysed, blood flow was reduced in three, oxygen metabolism was
      reduced in four, and OER was increased in four of seven unsedated patients,
      respectively. The sedated patients all had markedly reduced CBF and CMRO2 and OER
      in the high or supranormal range. CONCLUSION: Haemodynamic and metabolic
      disturbances proved to be common after SAH. These abnormalities probably reflect
      the primary brain injury caused by the initial haemorrhage. The impact of
      secondary insults such as acute hydrocephalus, brain oedema, vasospasm, seizures,
      hypotension and hypoxaemia are likely to be dependent on the degree of primary
      injury, which can be assessed by PET.

PMID- 14653846
TI  - Cognitive impairment in isolated subtentorial stroke.
AB  - BACKGROUND: Recent case reports have implicated subtentorial lesions of the
      brainstem or cerebellum as part of the neurocognitive circuitry. AIM: To
      determine whether cognitive impairment is part of the neurological deficit in
      isolated brainstem (IBSS) or cerebellar stroke (ICS), using bedside screening and
      formal neurocognitive assessment of higher cortical function. METHODS: Accrual
      occurred through a hospital based stroke registry. Cognitive bedside tests and
      neuropsychological tests were employed for the detection of higher cortical
      function. Scores from each test were converted to age and education based z
      scores. Scores at or below -1.5 SD were clinically defined 'impaired'. Scores
      were averaged across tests in each functional area. RESULTS: Of the stroke
      patients (n = 1360), the infarct was isolated within the brainstem (IBSS) in (45
      of 120 or 38%) and isolated within the cerebellum (ICI) in (37 of 79 or 46.8%).
      Comparison of the IBSS patients with cognitive impairment in one or more domains
      to those with brainstem (24 of 45 or 53%) and hemispheric cerebral infarcts: (43
      of 72 or 58%) (Pearson Chi Square) was not significantly different (P = 0.49).
      The admission Canadian Neurological Score (mean 10.2, 95% CI: 9.7-10.2) and
      Rankin score at 1 month (mean 1.7, 95% CI: 2.1-1.4). Comparison of the number of
      ICI patients with cognitive impairment in one or more domains (13 of 37 or 35.1%)
      to those with cerebellar and hemispheric cerebral infarcts who had abnormal
      cognitive testing in one or more domains (16 of 36 or 44.4%) (Pearson Chi Square)
      was not significantly different (P = 0.41). The mean admission Canadian
      Neurological Scores for the ICI cases was 10.9 (95% CI: 10.5-11.2) on average.
      Their mean admission Rankin score was 1.7 (95% CI: 1.4-2.1). Neuropsychological
      testing for frontal/executive skills, immediate and delayed memory, and
      visuospatial abilities (n = 15), revealed that frontal abilities were most
      impacted by the isolated strokes in these patients (average frontal impairment
      index = -1.29 +/- 0.79) followed by delayed recall of verbal and visual
      information (mean = -1.18 +/- 1.17). Immediate memory (-0.51 +/- 0.75) and
      visuoconstructive skills (-0.06 +/- 0.88) were relatively spared. Overall, 47% of
      the patients showed impairment on frontal tasks while 40% had significant
      impairment in delayed recall. In contrast, only 13% had scores below the cutoff
      for immediate memory and none fell below the cutoff for visuoconstructive skills.
      CONCLUSION: Cognitive impairment is a common sequel of isolated subtentorial
      stroke. The frequency of impairment is similar either because of isolated
      brainstem or isolated cerebellar infarct, and similar to cognitive impairment
      with cerebral hemispheric lesions. Frontal networks or metacognition is the most
      frequently involved domain.

PMID- 14653848
TI  - Receptor changes in cerebral arteries after subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH), occurring with a delay of 4-10 days is linked to
      cerebral vasospasm (CVS), a pathological constriction of the cerebral arteries.
      Several agents have been suggested as being responsible - amongst these perhaps 5
      hydroxytryptamine (5-HT) and endothelin-1 (ET-1) are the most prominent, given
      their ability to elicit powerful constriction of arteries. Investigating both 5
      HT and ET receptors we observed distinct changes in the receptor phenotype after
      experimental SAH - namely upregulation of the ETB and 5-HT1B receptors - linked
      to a higher sensitivity to the endogenous agonists. This multiple receptor
      upregulation may explain the failure in treating CVS using single receptor
      antagonists, and may also significantly change our understanding of the effector
      mechanism behind CVS. So far only the ET and 5-HT receptors have been studied in
      this regard, but other receptor systems may also undergo changes.

PMID- 14653849
TI  - Differential effects of various treatment combinations on cardiovascular
      dysfunction in patients with Parkinson's disease.
AB  - OBJECTIVES: Patients with Parkinson's disease (PD) frequently suffer from
      cardiovascular dysfunction, which may be enhanced to various extents by different
      antiparkinsonian drugs. MATERIALS AND METHODS: We analysed electrocardiogram
      (ECG) abnormalities, cardiovascular reflexes (CVR) and orthostatic hypotension
      (OH) in 148 patients with idiopathic PD assigned to five different combination
      therapies of levodopa (LD) plus either bromocriptine (BRO), ropinirole (ROP),
      selegiline (SEL), anticholinergic (ACH) or amantadine (AMA) or to LD monotherapy
      before and after a 1-week washout of the add-on drug. Patients were matched for
      age and disease severity (Hoehn and Yahr stage 2-3). Rater-blinded cardiovascular
      testing was performed at baseline, and following a 1-week washout period of the
      add-on drugs. RESULTS: We found that the incidence of cardiovascular dysfunction
      was generally higher in patients receiving a combination therapy compared with
      patients on LD monotherapy. ECG abnormalities were found in 40-52% of patients in
      combination therapy, but in only 20% of the patients receiving LD monotherapy.
      After discontinuation of BRO and SEL, there were significant improvements in ECG,
      OH and CVR. After washout of ACH and AMA, a significant improvement was found
      only in the CVR score. AMA and ROP were the add-on drugs with the least adverse
      cardiovascular effects. CONCLUSION: We conclude that pre-existing cardiovascular
      autonomic dysfunction should be investigated and taken into account when deciding
      which combination therapy to choose in the treatment of parkinsonian patients.

PMID- 14653850
TI  - Unchanged striatal dopamine transporter availability in narcolepsy: a PET study
      with [11C]-CFT.
AB  - OBJECTIVE: To investigate dopamine reuptake sites (dopamine transporter) in the
      caudate nucleus and putamen in narcolepsy. PATIENTS AND METHODS: Ten patients
      with narcolepsy and 15 controls were studied with positron emission tomography. A
      cocaine analogue [11C]-CFT was used as a radioligand. RESULTS: The uptake of[11C]
      CFT was within normal limits (89% of age-adjusted control mean in the caudate
      nucleus and 91% in the putamen) in patients with narcolepsy. CONCLUSIONS: No
      evidence of altered striataldopamine transporter availability was found in
      narcolepsy.

PMID- 14653851
TI  - Polysomnography in patients with intracranial tumors before and after operation.
AB  - OBJECTIVE: To evaluate the breathing and sleep patterns in patients with brain
      tumors before and after operation, and assess their relation to the location and
      size of the tumor, as well as to the post-operative outcome. METHODS:
      Polysomnographic studies were performed in 11 patients with intracranial tumors
      (nine supra- and two infratentorial) before and after surgery. RESULTS: Pre
      operatively, the mean apnea-hypopnea index (AHI) was 23.3. Six patients
      demonstrated signs of obstructive sleep apnea (SA) and one had mixed obstructive
      and central type SA. After operation, the mean AHI decreased to 8.1(P < 0.05).
      The duration of random eye movement sleep stage increased after tumor removal (P
      < 0.04). No relation was found between the characteristics of the tumor, nor the
      post-operative outcome and SA. CONCLUSIONS: Patients with brain tumors often
      suffer from SA and this can further worsen their symptoms related to increased
      intracranial pressure. Removal of the tumor results in a substantial decrease in
      sleep-related disturbances and may thus play a role in clinical recovery.

PMID- 14653852
TI  - Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy
      in multiple sclerosis?
AB  - BACKGROUND: Interferon beta (INFbeta) may induce the expression of several
      proteins, including neopterin, considered a biological marker of INFbeta
      activity. OBJECTIVES: The aim of this study was to determine the serum neopterin
      concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing
      remitting multiple sclerosis (r-r MS) patients, and to look for a possible
      correlation between protein synthesis and the clinical course of the disease.
      METHODS: Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week)
      for 2 years. Blood samples for neopterin determinations were taken daily over a
      period of 1 week at the end of each 6 months of therapy, and tested for
      neutralizing antibodies (NABs). RESULTS: Neopterin levels peaked 24-48 h post
      injection and returned to baseline after 120 h. After 1 year of therapy, four
      patients dropped out of the study because of progression of the disease: in these
      subjects a significant decrement of neopterin was observed. CONCLUSION: Neopterin
      baseline values were not found to decrease over the 2 years of therapy, and
      neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

PMID- 14653853
TI  - Long-term persisting interferon beta-1b neutralizing antibodies after
      discontinuation of treatment.
AB  - OBJECTIVES: Neutralizing antibodies (NAB) against interferon beta (IFNB) with
      presumably negative impact on treatment outcome have been described in up to 42%
      of patients undergoing IFNB treatment. However, in most cases NAB decrease
      despite continuation of IFNB therapy. Observations on NAB after discontinuation
      of IFNB therapy are lacking. Here, we report for the first time on NAB which now
      persist for several years following discontinuation of IFNB treatment. MATERIALS
      AND METHODS: We present two multiple sclerosis patients followed over 8 and 10
      years. NAB have been measured repeatedly and are presented together with clinical
      data. NAB developed after 2 years of treatment and persisted despite
      discontinuation of treatment at high titers for more than 4 years. CONCLUSION:
      Our data indicate that IFNB therapy may induce long-term NAB production which
      persists even after discontinuating IFNB treatment. Possible immunological
      mechanisms are discussed.

PMID- 14653854
TI  - Serum tumour necrosis factor-alpha and soluble tumour necrosis factor receptors
      levels in patients with Guillain-Barre syndrome.
AB  - OBJECTIVES: To estimate the serum concentrations of Tumour Necrosis Factor alpha
      (TNF-alpha) and soluble TNF receptors (s TNF-RI and TNF-RII) in patients with
      Guillain-Barre syndrome (GBS), before and after treatment. MATERIAL AND METHODS:
      The serum TNF-alpha and the soluble TNF receptors concentrations were measured by
      a sandwich enzyme-linked immunosorbent assay (ELISA) in 47 patients with GBS
      before and after the treatment - IVI therapy (n=26); Plasma Exchange (n=21).
      RESULTS: At the time of admission, the serum TNF-alpha concentrations were
      elevated (32.5-182.5 pg/ml) in 41/47 GBS patients (87.2%). Following the
      treatment (IVIG or PE), there was a significant decrease in the serum TNF-alpha
      concentrations (8.5-58.5 pg/ml) in these 41 GBS patients. The soluble TNF
      receptors, particularly sTNF-RII concentrations were significantly increased in
      GBS patients treated by IVIG therapy. CONCLUSIONS: The results of this indicated
      that (a) Elevated serum concentrations of TNF-alpha showed a positive correlation
      with the disease severity in patients with GBS. (b) The decrease in the serum TNF
      alpha and increase in the serum soluble TNF receptors, particularly sTNF-RII
      showed a positive correlation with the neurological recovery in GBB patients
      following treatment.

PMID- 14653855
TI  - Expanded GAA repeats and clinical variation in Friedreich's ataxia.
AB  - INTRODUCTION: One of the main features of Friedreich's ataxia (FA) is phenotypic
      variability that can now be explained by the molecular mechanism (GAA expansion)
      underlying the disease. MATERIALS AND METHODS: We have analyzed genotype
      phenotype correlations in a group of 40 patients homozygous for the GAA
      expansion. RESULTS: The smaller GAA expansion (GAA1 allele) size correlated with
      age at onset and progression disease rate, but we found no correlation between
      the larger GAA expansion (GAA2 allele) size and these clinical parameters. The
      frequency of pes cavus, scoliosis, axonal sensory neuropathy and areflexia
      increased with the size of GAA1, whereas some signs such as sphincter
      disturbances, cerebellar atrophy on MRI, amyotrophy, dysarthria and decreased
      vibration sense were associated with increased duration of the disease.
      CONCLUSION: GAA1 size is the main determinant of FA phenotype and GAA2 size is a
      poor predictor of clinical variation. Some clinical features are independent of
      GAA1 and GAA2 sizes and are determined by the duration of the disease.

PMID- 14653856
TI  - Use of the capture-recapture method for epidemiological studies in determining
      prevalence.

PMID- 14653861
TI  - Impact of INTACT: do we change the target or the aim?

PMID- 14653859
TI  - Protein identification from two-dimensional gel electrophoresis analysis of
      Klebsiella pneumoniae by combined use of mass spectrometry data and raw genome
      sequences.
AB  - Separation of proteins by two-dimensional gel electrophoresis (2-DE) coupled with
      identification of proteins through peptide mass fingerprinting (PMF) by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) is the widely used technique for proteomic analysis. This approach relies,
      however, on the presence of the proteins studied in public-accessible protein
      databases or the availability of annotated genome sequences of an organism. In
      this work, we investigated the reliability of using raw genome sequences for
      identifying proteins by PMF without the need of additional information such as
      amino acid sequences. The method is demonstrated for proteomic analysis of
      Klebsiella pneumoniae grown anaerobically on glycerol. For 197 spots excised from
      2-DE gels and submitted for mass spectrometric analysis 164 spots were clearly
      identified as 122 individual proteins. 95% of the 164 spots can be successfully
      identified merely by using peptide mass fingerprints and a strain-specific
      protein database (ProtKpn) constructed from the raw genome sequences of K.
      pneumoniae. Cross-species protein searching in the public databases mainly
      resulted in the identification of 57% of the 66 high expressed protein spots in
      comparison to 97% by using the ProtKpn database. 10 dha regulon related proteins
      that are essential for the initial enzymatic steps of anaerobic glycerol
      metabolism were successfully identified using the ProtKpn database, whereas none
      of them could be identified by cross-species searching. In conclusion, the use of
      strain-specific protein database constructed from raw genome sequences makes it
      possible to reliably identify most of the proteins from 2-DE analysis simply
      through peptide mass fingerprinting.

PMID- 14653860
TI  - Dynamic localization of SPE-9 in sperm: a protein required for sperm-oocyte
      interactions in Caenorhabditis elegans.
AB  - BACKGROUND: Fertilization in Caenorhabditis elegans requires functional SPE-9
      protein in sperm. SPE-9 is a transmembrane protein with a predicted extracellular
      domain that contains ten epidermal growth factor (EGF)-like motifs. The presence
      of these EGF-like motifs suggests that SPE-9 is likely to function in gamete
      adhesive and/or ligand-receptor interactions. RESULTS: We obtained specific
      antisera directed against different regions of SPE-9 in order to determine its
      subcellular localization. SPE-9 is segregated to spermatids with a pattern that
      is consistent with localization to the plasma membrane. During spermiogenesis,
      SPE-9 becomes localized to spiky projections that coalesce to form a pseudopod.
      This leads to an accumulation of SPE-9 on the pseudopod of mature sperm.
      CONCLUSIONS: The wild type localization patterns of SPE-9 provide further
      evidence that like the sperm of other species, C. elegans sperm have molecularly
      mosaic and dynamic regions. SPE-9 is redistributed by what is likely to be a
      novel mechanism that is very fast (approximately 5 minutes) and is coincident
      with dramatic rearrangements in the major sperm protein cytoskeleton. We conclude
      that SPE-9 ends up in a location on mature sperm where it can function during
      fertilization and this localization defines the sperm region required for these
      interactions.

PMID- 14653862
TI  - Gemcitabine/carboplatin in advanced non-small-cell lung cancer: data from
      randomized phase III trials.

PMID- 14653863
TI  - Cell-cycle inhibitors as novel therapies for lung cancer.

PMID- 14653864
TI  - Small-cell lung cancer: state of the art.
AB  - Thirty years ago, there was a pervasive atmosphere of pessimism concerning the
      management of small-cell lung cancer (SCLC). Surgery or radiation therapy alone
      resulted in few cures since these techniques utilize a local therapy for a
      disseminated disease. Chemotherapy remains the backbone of treatment for all
      patients with SCLC, regardless of stage. For patients with limited-stage disease
      (LD), the addition of thoracic radiation to chemotherapy is standard. The optimal
      timing, dose, and schedule of radiation remains undefined. The majority of
      studies demonstrate equivalent or superior survival for early radiation when
      compared to delayed radiation. Approximately 50% of patients with LD will achieve
      a complete remission with chemoradiation and will be candidates for prophylactic
      cranial irradiation (PCI). While phase III trials have failed to demonstrate a
      statistically significant survival for PCI, brain relapse is clearly reduced, and
      a metaanalysis reports a small long-term survival advantage favoring patients
      receiving PCI. Unfortunately, unlike LD SCLC, advances in extensive-stage disease
      have been elusive, despite the testing of numerous strategies. Four courses of
      cisplatin (or carboplatin) plus etoposide remain standard first-line therapy.
      Promising results have been seen with irinotecan/cisplatin, but confirmatory
      trials are still needed. A plateau has been reached with chemotherapy regimens,
      and novel strategies are greatly needed to improve survival for patients with
      SCLC.

PMID- 14653865
TI  - Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2
      non-small-cell lung cancer.
AB  - Preoperative chemotherapy in patients with stage III non-small-cell lung cancer
      (NSCLC) remains controversial. Phase II trials utilizing preoperative
      chemotherapy in selected patients have achieved complete resection rates of 50%
      70% with 3-5 year failure-free survival rates of 15%-33%. Between October 1992
      and November 1994, 57 adults (50 of whom were evaluable) with surgically staged
      IIIA NSCLC and pathologically documented ipsilateral mediastinal nodal
      involvement (N2) were enrolled in a Cancer and Leukemia Group B randomized trial.
      Preoperative therapy was thought to be critical to facilitating surgical
      resectability. For patients randomized to the radiotherapy/surgery/radiotherapy
      (RSR) arm (n = 24), treatment consisted of preoperative radiation therapy (RT) at
      40 Gy, surgery, and then additional RT at 14-20 Gy. For patients randomized to
      the chemotherapy/surgery/chemotherapy/radiotherapy (CSCR) arm (n = 26), treatment
      consisted of 2 cycles of cisplatin/etoposide with filgrastim support (PE)
      followed by surgery, 2 more cycles of PE, then RT 54-60 Gy. The total dose of RT
      on either arm was 54 Gy if completely resected or 60 Gy if incompletely resected
      or unresected. Clinical characteristics were well balanced between the two arms.
      Thoracotomy was performed in 42 patients (84%), 28 (67%) of whom had complete
      resection. The median failure-free and overall survival rates were 12 months (95%
      confidence interval [CI], 9-23 months) and 23 months (95% CI, 19 months-infinity)
      for the RSR arm and 11 months (95% CI, 5-20 months) and 18 months (95% CI, 12-32
      months) for the CSCR arm. The rates of overall and complete surgical resection,
      downstaging of nodal involvement, and failure-free (P = 0.92) and overall
      survival (P = 0.41) did not differ between the two treatment arms. Moreover, in
      this trial, the chemotherapy regimen was sufficiently toxic to have had a lower
      completion rate of prescribed therapy in the CSCR arm than in the RSR arm.

PMID- 14653866
TI  - Real-time clinical application of quality-of-life assessment in advanced lung
      cancer.
AB  - In the management of advanced non-small-cell lung cancer (NSCLC), quality of life
      (QOL) is a very important consideration when determining therapy. However,
      clinicians and patients generally make their treatment decisions based upon
      informal appraisal of QOL rather than formal assessment. Previously, we showed
      that Functional Assessment of Cancer Therapy-Lung (FACT-L) data were highly
      prognostic of survival in advanced NSCLC, suggesting the potential value of FACT
      L scores for treatment decision making. A key barrier is the impracticality and
      burden of real-time administration and scoring of paper forms in the clinic.
      Handheld and touch screen computer administration and scoring can address that
      barrier. This pilot study assessed the feasibility of using computer technology
      to aid in the collection and interpretation of QOL and selected clinical data in
      real time, reducing human effort. The technology was found to be acceptable to
      patients and staff and feasible within the clinical setting. Integrating formal
      QOL assessment into treatment decision making in a clinical oncology setting
      requires further evaluation.

PMID- 14653867
TI  - The importance of quality-of-life measurements in oncology.

PMID- 14653868
TI  - Promising developments in targeted therapies for non-small-cell lung cancer.
AB  - Despite advances in chemotherapy, radiation therapy, and surgery, the overall
      survival for patients with lung cancer remains poor. Thus, novel therapeutic
      approaches are warranted. As knowledge of the molecular abnormalities and
      dysregulated cellular processes contributing to the pathogenesis and progression
      of lung cancer has been acquired, intense interest has been directed at
      developing agents that target these abnormalities. New agents targeting aberrant
      receptor tyrosine kinases, the Ras oncoprotein, mediators of metastases and
      angiogenesis, and the tumor suppressor gene p53 have, among other agents, shown
      promise in preclinical studies. Early clinical trials with these agents in
      patients with advanced malignancies suggest preliminary evidence of clinical
      activity and possible applications in non-small-cell lung cancer (NSCLC). Ongoing
      clinical trials will help clarify the settings in which these agents are of
      greatest therapeutic value, the optimal schedule of administration, toxicities
      associated with chronic administration, and hopefully, provide additional insight
      into the biology of lung cancer. Selected clinical trials will be presented to
      highlight the use of rationally designed, targeted therapies for patients with
      NSCLC.

PMID- 14653869
TI  - "Targeted" therapies for non-small cell lung cancer.

PMID- 14653870
TI  - Doublet chemotherapy for advanced non-small cell lung cancer.

PMID- 14653871
TI  - 38th annual meeting of the American Society of Clinical Oncology. Orlando,
      Florida. May 18-21, 2002.

PMID- 14653872
TI  - Activity of ZD1839 (Gefitinib, Iressa) in previously treated patients with
      recurrent and advanced non-small-cell lung cancer.

PMID- 14653873
TI  - Chemotherapy in advanced non-small-cell lung cancer: a look behind and ahead.
AB  - Lung cancer is still the leading cause of cancer-related deaths in Western
      countries. The 5-year survival rate in 2002 remains dismal. In advanced disease,
      chemotherapy is the cornerstone of treatment, but a crucial step is whether the
      impact of chemotherapy in the management of this disease justifies either the
      toxicity on patients or the always-rising costs. A number of randomized trials
      demonstrated a prolonged survival for patients treated with chemotherapy compared
      with best supportive care. However, newer platinum-based combination regimens
      have failed to take a major step forward; chemotherapy alone has reached a
      plateau of activity that could be partially solved by integrating molecular
      targeted strategies in clinical practice. Quality of life remains a key issue in
      clinical decisions for metastatic patients. New answers will come by encouraging
      all fit patients to join clinical trials.

PMID- 14653874
TI  - Use of postoperative radiotherapy for node-positive non-small-cell lung cancer.
AB  - The appropriate patient selection for adjuvant radiotherapy after primary
      surgical therapy of non-small-cell lung cancer (NSCLC) is unclear. Four thousand
      thirteen patients diagnosed from 1988-1995 in 9 registry areas of the Survival,
      Epidemiology, and End Results program who received primary surgical therapy for
      pathologic stage T1-3 N1/2 M0 NSCLC were identified. County-level and patient
      specific variables associated with the use of postoperative radiotherapy (PORT)
      were studied by multivariate logistic regression analysis. Prognostic factors for
      cause-specific survival (CSS) and overall survival (OS) were determined by Cox
      multivariate analysis. Overall, 58% of node-positive patients received PORT. Use
      of PORT was independently associated with younger age, more advanced nodal
      disease, no prior cancer, less extensive surgery than pneumonectomy, and patient
      residence close to a radiotherapy facility. In multivariate analysis of the
      entire node-positive population, there were no differences in OS or CSS with the
      use of PORT. In the patients with N2 disease, PORT was associated with improved
      OS (5-year OS: 16% without PORT, 22% with PORT; P = 0.001) and CSS (5-year CSS:
      25% without PORT, 30% with PORT; P = 0.02). Additionally, patients with = 4 nodes
      involved also had an improved survival in association with PORT (5-year OS: 11%
      without PORT, 18% with PORT; P = 0.001; 5-year CSS: 17% without PORT, 25% with
      PORT; P = 0.009). Therefore, recognizing the inherent limitations of a
      retrospective, registry-based analysis, patients with more advanced nodal disease
      appear to have an improved survival with the use of PORT.

PMID- 14653875
TI  - The possible use of uniform PORT doses is important in the SEER analysis, but
      undetected selection bias remains an issue.

PMID- 14653876
TI  - Unfavorable therapeutic index of cisplatin/gemcitabine/vinorelbine in advanced
      non-small-cell lung cancer.
AB  - In view of favorable reports with the 3-drug combination of PGV
      (cisplatin/gemcitabine/vinorelbine), this multicenter phase II study evaluated
      the therapeutic index of PGV in patients with advanced non-small-cell lung cancer
      (NSCLC). Thirty-two patients with stage IV NSCLC and 1 with stage IIIB were
      studied. There were 23 men and 10 women, with a median age of 63 years (range, 38
      80 years). Twelve patients had a performance status (PS) of 0, and 21 patients
      had a PS of 1. Treatment consisted of cisplatin 50 mg/m2, gemcitabine 1000 mg/m2,
      and vinorelbine 25 mg/m2 all given intravenously on days 1 and 8, in 21-day
      cycles. Fifteen patients (45%; 95% confidence interval (CI), 28%-64%) achieved a
      partial response. Median response duration was 3 months (range, 1-9 months). The
      median and 1-year survival rates were 9.4 months and 39% (95% CI, 23%-58%),
      respectively. The median number of cycles was 4. Only 3 patients (9%) completed
      treatment without regimen modifications. Median dose intensity (% planned) was
      cisplatin 24 mg/m2/week (72%), gemcitabine 483 mg/m2/week (72%), and vinorelbine
      12 mg/m2/week (72%). Toxicities were predominantly hematologic, with grade 3/4
      neutropenia (67%), febrile neutropenia (21%), and thrombocytopenia (67%). There
      were 3 (9%) treatment-related deaths due to neutropenic complications. This study
      confirms the substantial antineoplastic activity of PGV. We observed a high rate
      of severe hematologic toxicity, especially febrile neutropenia, despite a lower
      delivered dose intensity of PGV. Given these results, PGV appears to offer no
      therapeutic advantage to current doublet regimens.

PMID- 14653877
TI  - Hypersensitivity pneumonitis in advanced non-small-cell lung cancer patients
      receiving gemcitabine and paclitaxel: report of two cases and a review of the
      literature.
AB  - Gemcitabine (2'-2'-difluorodeoxycytidine) is a recently developed pyrimidine
      antagonist that is structurally related to cytarabine (ara-C). When
      phosphorylated intracellularly, gemcitabine inhibits ribonucleotide reductase and
      arrests cell cycling in the S phase. Paclitaxel is a potent promoter and
      stabilizer of microtubule spindle formation and an inhibitor of cell cycling. In
      this report, we discuss 2 patients with advanced-stage non-small-cell lung cancer
      (NSCLC) treated with a combination of gemcitabine/paclitaxel who developed
      pulmonary symptoms of dyspnea and cough. Chest radiographs and computed
      tomography revealed diffuse pulmonary infiltrates. Bronchoscopic evaluation
      revealed diffuse alveolar damage with associated type II pneumocyte hyperplasia
      without evidence of infection or metastatic carcinoma, suggesting the development
      of a drug-induced pulmonary toxicity. Both cases improved with the
      discontinuation of gemcitabine/paclitaxel and with supportive care including
      steroids in one of the patients. We also review the published case reports of
      pneumonitis believed to be secondary to the taxanes or gemcitabine when used as
      single agents and a solitary case report describing pneumonitis in the setting of
      both a taxane and gemcitabine. Because the combination of gemcitabine/paclitaxel
      has demonstrated activity in NSCLC, the use of this combination is likely to
      increase. Clinicians caring for lung cancer patients receiving this combination
      should be aware of this potential pulmonary toxicity.

PMID- 14653878
TI  - The role of farnesyltransferase inhibitors in lung cancer therapy.
AB  - Protein farnesylation is required for the localization and function of several
      proteins pivotal to signal transduction pathways and cytoskeletal organization,
      including the Ras proteins. Ras proteins are constitutively activated in 30% of
      human tumors, including lung cancer tumors, as a consequence of mutations in ras
      genes. Farnesyltransferase inhibitors (FTIs) were thus designed to curtail the
      Ras-mediated aberrant signals that regulate cell proliferation, apoptosis,
      invasion, and angiogenesis. These processes are vital to the perpetuation of the
      malignant phenotype. However, current evidence suggests that the antitumor
      activity of FTIs is Ras-independent. This article reviews preclinical and
      clinical data pertinent to the use of FTIs in lung cancer.

PMID- 14653879
TI  - Farnesyltransferase inhibitors: a promising future in cancer treatment.

PMID- 14653881
TI  - Social representations of stem cell research and preimplantation genetic
      diagnosis.
AB  - The study examined public thinking about stem cell research and preimplantation
      genetic diagnosis (PGD) using social representation theory. Social representation
      theory is concerned with the movement of scientific knowledge from the realm of
      the specialist into lay knowledge. Participants were interviewed and the data
      analysed qualitatively. Three social representations were found for both stem
      cell research and PGD. For stem cell research, one was based on irrational fears,
      one was based on social concerns for the technology and the final was based on
      the notion of the 'slippery slope'. For PGD, the first social representation was
      based on concern for the human impact, the second was based, again, on irrational
      fear, and the third was based on medical applications. Participants rated stem
      cell research more positively than PGD. It was concluded that while information
      about both topics is in the process of being transformed, knowledge of stem cell
      research has been transformed into lay knowledge more completely than knowledge
      of PGD. Directions for future research included attitude surveys and discourse
      analyses.

PMID- 14653884
TI  - Cryopreservation as a tool to reduce multiple birth.
AB  - The potential role of embryo cryopreservation from the point of view of
      prevention of multiple pregnancies is analysed. Cryopreservation is an
      unavoidable option in stimulated IVF/intracytoplasmic sperm injection (ICSI), but
      at the same time an underestimated tool in the prevention of twins. There is a
      need for an evaluation system not only of the cryotechnology process per se, but
      also of the true augmenting effect of cryopreservation on the total reproductive
      potential of a single oocyte harvest. Only cryopregnancies occurring after an
      unsuccessful fresh cycle (possibly followed by one or more unsuccessful freeze
      thaw cycles with embryos from the same harvest) truly reflect the augmentation
      potential of cryopreservation. This potential is greater than generally thought.
      First, the efficacy of cryopreservation is suboptimal with survival rates between
      30 and 70%. Second, if single-embryo transfer were applied in a much larger
      proportion of cycles than is presently the case, more embryos would be available
      for cryopreservation, resulting in more and more successful freeze-thaw cycles.
      In the future, the combination of elective single-embryo transfer with an
      optimized cryopreservation programme is likely to become the standard of care for
      routine IVF/ICSI treatment.

PMID- 14653886
TI  - Resonance in the menstrual cycle: a new model of the LH surge.
AB  - In vertebrates, ovulation is triggered by a surge of LH from the pituitary. The
      precise mechanism by which rising oestradiol concentrations initiate the LH surge
      in the human menstrual cycle remains a fundamental open question of reproductive
      biology. It is well known that sampling of serum LH on a time scale of minutes
      reveals pulsatile release from the pituitary in response to pulses of
      gonadotrophin releasing hormone from the hypothalamus. The LH pulse frequency and
      amplitude vary considerably over the cycle, with the highest frequency and
      amplitude at the midcycle surge. Here a new mathematical model is presented of
      the pituitary as a damped oscillator (pulse generator) driven by the
      hypothalamus. The model LH surge is consistent with LH data on the time scales of
      both minutes and days. The model is used to explain the surprising pulse
      frequency characteristics required to treat human infertility disorders such as
      Kallmann's syndrome, and new experimental predictions are made.

PMID- 14653882
TI  - Ethical issues in modern biological technologies.
AB  - Today's biology-based technologies have emerged from a historical imperative and
      as an inevitable consequence of developments in modern biology beginning in the
      last half-century. They can be classified into almost 30 different areas, ranging
      from the use of gene therapy for human beings, enzyme engineering, stem cells and
      cloning, to marine biotechnology, bioinformatics, nanotechnology and biological
      warfare among many others. Many of them have major sociopolitico-economic, moral,
      ethical and legal implications. They include genetic engineering, gene therapy,
      tissue culture, stem cell work, the new DNA technologies, commercialization of
      traditional plant-based drug formulations, assisted reproduction techniques,
      cloning technologies, organ transplantation, bioinformatics, and biological
      weapons. Examples of the ethical implications of several of these items will be
      considered. They will be assessed with special reference to ethical implications
      in respect of assisted reproduction techniques, of worldwide importance today,
      particularly for a country such as India.

PMID- 14653888
TI  - Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix)
      and single-dose long GnRH agonist (goserelin) protocol for IVF cycles--a
      prospective, randomized study.
AB  - This prospective randomized study compared the effectiveness of a flexible single
      dose gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) and a single
      dose long GnRH agonist (goserelin) protocol for ovarian stimulation in
      IVF/intracytoplasmic sperm injection (ICSI) cycles. All patients from the waiting
      list were successively included in the study, pre-programmed with an oral
      contraceptive, and randomized into goserelin and cetrorelix groups. Depending on
      the date on which their menstrual period started, patients took oral
      contraceptives for one or two cycles. Ultimately, 236 patients in the first group
      received a single dose of depot preparation of goserelin and 224 patients
      received a single 3 mg dose of cetrorelix in the late follicular phase, when the
      mean follicle diameter exceeded 12 mm. The mean number of ampoules of FSH and the
      duration of stimulation was statistically significantly lower in the cetrorelix
      group than in the goserelin group (25.9 versus 34.5, and 9.6 versus 12.2 days, P
      < 0.01). The mean number of oocytes retrieved was similar (6.7 +/- 4.5 versus 7.2
      +/- 4.6, NS). Similar results were observed in fertilization rates, blastulation
      rates and blastocyst transfer rates in both groups. Clinical pregnancy and
      delivery rates per cycle were higher in the goserelin group (34.3 and 30.1%) than
      in the cetrorelix group (31.9 and 28.3%), but the differences were not
      statistically significant. The flexible single-dose GnRH antagonist protocol is
      an advantageous alternative to the long GnRH agonist protocol, with similar
      efficacy, shorter duration, a significant reduction in the number of FSH ampoules
      used and without the menopause-like effects of the GnRH antagonist.

PMID- 14653889
TI  - Effect of ovarian stimulation on plasma lipid and apolipoprotein concentrations
      in a population of infertile women undergoing IVF/embryo transfer.
AB  - Twenty consecutive infertile women (mean age +/- SD, 36.9 +/- 5.4 years)
      undergoing ovarian stimulation with recombinant follicle stimulating hormone
      (rFSH) were recruited. Serial measurements of plasma total cholesterol, low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (Apo-B),
      lipoprotein(a) (Lp(a)), oestradiol and progesterone were performed on day 3
      before starting ovarian stimulation, on the day of human chorionic gonadotrophin
      (HCG) administration and on day 15 after HCG administration, respectively. The
      relationship between lipid and apolipoprotein concentrations and serum oestradiol
      and progesterone concentrations was sought. All women completed the ovarian
      stimulation protocol successfully. Plasma concentrations of HDL-C and Apo-A1 were
      significantly raised on the day of HCG administration and then returned to
      baseline values within 2 weeks. LDL-C, TG, Apo-B and Lp(a) were significantly
      increased on day 15 after HCG administration. Lp(a) variation between the first
      sample and the third sample correlated positively with serum progesterone
      concentrations (r = 0.472, P < 0.04). No other significant correlations were
      found between lipid and apolipoprotein variations and either oestradiol or
      progesterone concentrations. It was concluded that an increase of plasma lipid
      and apolipoprotein concentrations deserves particular consideration and all women
      undergoing ovarian stimulation should be monitored for long-term atherogenic and
      thrombogenic risks.

PMID- 14653891
TI  - Reproductive outcome of polycystic ovarian syndrome patients treated with GnRH
      antagonists and recombinant FSH for IVF/ICSI.
AB  - The purpose of this prospective study was to assess the reproductive outcome of
      patients with polycystic ovarian syndrome (PCOS) treated by in-vitro
      fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with recombinant FSH
      (rFSH) and gonadotrophin releasing hormone (GnRH) antagonists. One hundred and
      ten patients were evaluated. The starting dose of rFSH was 100 IU in 67 women
      with body mass index (BMI) </=29 kg/m(2) and 200 IU in 43 women with BMI >29
      kg/m(2). GnRH antagonist was started by the detection of a follicle of a 15mm in
      ultrasound scan. A significantly lower ongoing pregnancy rate per oocyte
      retrieval (25.6% versus 46.7%, P = 0.04) and a higher occurrence of ovarian
      hyperstimulation syndrome (16.3% versus 3.0%, P = 0.03) was observed in the group
      of patients with BMI >29 kg/m(2) as compared with the group of patients with BMI
      </=29 kg/m(2), respectively. In conclusion, in GnRH antagonist cycles a worse
      reproductive outcome is expected in PCOS patients with BMI >29 kg/m(2) in whom
      stimulation is initiated with 200 IU of rFSH as compared with PCOS patients with
      BMI </=29 kg/m(2) in whom stimulation is initiated with 100 IU of rFSH.

PMID- 14653893
TI  - Administration of recombinant human FSH (solution in cartridge) with a pen device
      in women undergoing ovarian stimulation.
AB  - This study evaluated the first multiple-use pen device for the self
      administration of recombinant FSH. The pen device is used for the subcutaneous
      injection of a pre-mixed ready-to-use solution of follitropin beta from a
      multiple-dose cartridge, and has flexible dosing capabilities. In the ease-of-use
      questionnaire, 90% of subjects rated the overall experience of self-injecting
      follitropin beta using the pen device as 'very good' (on day 6). The
      comprehension questionnaire revealed that prior to the first injection and during
      the second injection, the follitropin beta cartridge was properly loaded into the
      pen device by 96.7 and 100% of the subjects respectively. The questionnaire also
      showed that the correct dose was selected and self-administered by 98.3 and 100%
      of the subjects respectively. Biochemical and ongoing pregnancy rates per attempt
      were 56.7 and 45.0% respectively. The pen device is safe, effective, and easy to
      use for self-administering recombinant FSH during ovarian stimulation.

PMID- 14653894
TI  - Amenorrhoea revealing an arteriovenous uterine malformation, and recovery of
      menses after embolization.
AB  - A case is reported of secondary amenorrhoea related to an arteriovenous
      malformation (AVM) successfully treated with embolization, with a recovery of
      menstrual cycles. A 28-year-old woman presented with secondary amenorrhoea as the
      only clinical symptom. Although she had an eugonadic status, there was no genital
      withdrawal bleeding upon cessation of an oral contraceptive. Pelvic transvaginal
      ultrasonography revealed a pelvic mass but magnetic resonance imaging (MRI)
      clearly showed an AVM. Classical angiography was performed with endovascular
      embolization. Partial thrombosis of the lesion was assessed by magnetic resonance
      angiography. Recovery of menses occurred 2 months later. It is speculated that
      blood stolen from the endometrium by the uterine AVM could have been responsible
      for the amenorrhoea. It is a very unusual cause, and it can be successfully
      treated with embolization.

PMID- 14653895
TI  - The ultrastructure of mouse embryonic stem cells.
AB  - The fine structure of mouse embryonic stem (ES) cell colonies was analysed by
      scanning and transmission electron microscopy. Most of the ES cells had numerous
      microvilli of different lengths. Coated pits and vesicles were also seen along
      areas of the peripheral cytoplasm and plasma membranes. Junctional complexes
      including gap junctions were observed between adjacent ES cells. These cells had
      Golgi complexes, spherical to oval mitochondria, lysosomes and typical
      centrioles, microfilaments and microtubules and large nuclei containing
      reticulated nucleoli. These results are consistent with the ultrastructural
      features of undifferentiated cells.

PMID- 14653896
TI  - Is there any predictive value of first polar body morphology for embryo genotype
      or developmental potential?
AB  - The first polar body (PB1) was previously used for genotyping oocytes in
      preimplantation genetic diagnosis (PGD) for Mendelian and chromosomal disorders.
      A possible use of PB1 morphology for predicting developmental potential was also
      explored in a few retrospective studies, which showed controversial results. PB1
      morphology was evaluated in a prospective study of 831 oocytes, which were then
      followed up through preimplantation development, with analysis of fertilization
      rate, embryo quality, survival to blastocyst, and outcome of embryo transfer,
      demonstrating no correlation with PB1 morphology. There was also no evidence for
      a PB1 predictive value for these parameters either in good or poor responder
      patients. An additional 358 oocytes and embryos from patients requesting PGD were
      tested for aneuploidies, revealing no relationship with PB1 morphology either.
      This suggests that PB1 morphology may not be a reliable predictor of genotype or
      the developmental potential of the corresponding oocytes or embryos.

PMID- 14653897
TI  - Preimplantation diagnosis of Lesch-Nyhan using mini-sequencing primer extension.
AB  - Lesch-Nyhan syndrome (LN) is a severe X-linked disorder of males characterized by
      hyperuricaemia, choreoathetosis, spasticity, mental retardation and self
      mutilation. The disorder is caused by a wide spectrum of mutations distributed
      throughout the hypoxanthine phosphoribosyltransferase (HPRT) gene. Female
      carriers of LN display no clinical symptoms but are at 50% risk of passing on the
      affected gene to their male offspring. A couple who had a boy with LN were
      referred to Monash IVF for preimplantation genetic diagnosis (PGD) because the
      woman had undergone tubal ligation and the couple wanted to have another child. A
      test was developed for the causative mutation IVS8+6 T-->G mutation based on
      minisequencing primer extension that also incorporated the co-analysis of an
      informative tetranucleotide marker in intron 3 of the HPRT gene to identify
      allelic dropout. All four biopsied embryos from their first IVF cycle were
      diagnosed as unaffected, and transfer of two embryos in the cohort with the
      highest morphological quality resulted in a singleton pregnancy and the birth of
      a healthy girl. Direct mutation detection by mini-sequencing and parallel
      analysis of an informative linked marker provides an alternative strategy for
      molecular diagnosis of point mutations that will have useful application in PGD
      for other single gene disorders.

PMID- 14653898
TI  - Results of preimplantation genetic diagnosis in patients with Klinefelter's
      syndrome.
AB  - With the application of preimplantation genetic diagnosis (PGD), a possible
      genetic contribution of spermatozoa obtained from 47,XXY non-mosaic Klinefelter
      patients on preimplantation embryos was analysed in eight couples. Interpretable
      fluorescence in-situ hybridization results were obtained for 28 out of 33 embryos
      biopsied (84.8%) and 23 blastomeres were analysed for chromosomes 13, 18, 21, X
      and Y. Nine out of 23 embryos were diagnosed as abnormal (39.1%). Five out of
      nine contained sex chromosome abnormalities (55.5%). Two were diagnosed as 47,XXY
      and three were found to have monosomy X. Besides sex chromosomal abnormalities,
      other abnormalities detected were haploidy, triploidy, monosomy 13, monosomy 18
      and trisomy 13. Five blastomeres were analysed for sex chromosomes only and all
      of them were found to be normal. Overall, the rate of sex chromosome abnormality
      in biopsied embryos was found to be 17.8% (5/28). Moreover, among 33 embryos
      biopsied, five of the eight zygotes, which were classified as a poor prognosis
      group according to pronuclear morphology scoring, showed an impaired growth
      profile after biopsy and were found to be chromosomally abnormal. Elimination of
      abnormal embyos and transfer of normal ones resulted in four pregnancies in eight
      cycles (50%). Two pregnancies, one singleton and one twins resulted in healthy
      births. Two pregnancies, one singleton and one twins are continuing beyond the
      second trimester. These results show that there is in fact elevated chromosomal
      abnormality for both sex chromosomes and autosomes in embryos developed from
      Klinefelter males. Furthermore together with PGD, embryo scoring according to
      pronuclear morphology can give additional benefit for selecting chromosomally
      abnormal embryos. Therefore, PGD should be recommended in cases with
      Klinefelter's syndrome and this information should be discussed with the couple
      when genetic counselling is given.

PMID- 14653899
TI  - Preimplantation genetic diagnosis as a novel source of embryos for stem cell
      research.
AB  - The generation of human embryonic stem (hES) cells has captured the public and
      professional imagination, largely due their potential as a means of overcoming
      many debilitating and degenerative diseases by cell replacement therapy. Despite
      this potential, few well-characterized hES cell lines have been derived. Indeed,
      in the UK, despite several centres having been active in this area for more than
      2 years, there are as yet no published reports of human embryonic stem cells
      having been generated. Part of the reason for this lack of progress may relate to
      the quality of embryos available for research. Embryos surplus to therapeutic
      requirements following routine assisted reproduction treatment are often of poor
      quality and a large proportion may be aneuploid. This study reports a new
      approach to hES cell derivation. Embryos surplus to therapeutic requirements
      following preimplantation genetic diagnosis were used. Although unsuitable for
      embryo transfer due to the high risk of genetic disease, these embryos are from
      fertile couples and thus may be of better quality than fresh embryos surplus to
      assisted reproduction treatment cycles. Embryos donated after cryopreservation
      were also used, and putative hES lines were derived from both sources of embryos.
      The cell lines described here are thought to be the first reported hES cell lines
      to have been derived in the UK.

PMID- 14653901
TI  - Hysteroscopic septum resection using the Versapoint system in subfertile women.
AB  - The aim of the present study was to assess the safety and efficacy of
      hysteroscopic septum resection by Versapoint. Forty-five subfertile patients who
      underwent hysteroscopic septum resection using the Versapoint system were
      analysed. A type Va and a type Vb septate uterus were present in 10 (22.2%) and
      35 (77.8%) patients respectively. Complete septum excision was feasible in all
      patients. No complications occurred during septum resection. Repeat hysteroscopy
      2 months after septum excision showed normal endometrial cavity in all patients.
      Hysteroscopic septum resection by Versapoint system is a safe and efficient
      method.

PMID- 14653902
TI  - The association between socioeconomic development at the town level and the
      distribution of dental caries in Brazilian children.
AB  - OBJECTIVE: To investigate the association between dental caries among children in
      the state of Sao Paulo, Brazil, and town-level indices of socioeconomic
      development. METHODS: We examined 15 385 oral-examination records from children
      aged 5 or 6 years old from 129 towns and cities in the state of Sao Paulo. We
      studied two outcomes: (1) the mean number of decayed, missing, and filled
      deciduous teeth (dmft index) and (2) the care index, which is the proportion of
      decayed teeth that have already been filled. The explanatory variables were the
      child development index, human development index, illiteracy rate among subjects
      older than 20 years, household income, Gini coefficient, insufficient income,
      fluoridated water supply, number of dentists per 10 000 inhabitants, number of
      dentists in the public service per 10 000 inhabitants, and number of weekly hours
      of dentist work in the public service per 10 000 inhabitants. Multiple linear
      regression models were fitted to the two outcome variables (dmft index and care
      index). RESULTS: The multiple linear regression analysis showed that a higher
      dmft index was associated with a low child development index, a high illiteracy
      rate, and an unfluoridated water supply. The child development index was
      significantly associated with the care index, and the number of dentists in the
      public service per 10 000 inhabitants showed borderline statistical significance.
      CONCLUSIONS: Our results indicate that town-level indices of socioeconomic status
      are significantly correlated with caries indices. Our results also emphasize the
      beneficial effect that fluoridating water has on reducing the prevalence of
      dental caries and the fact that strategies for treating and preventing oral
      diseases should be emphasized within the context of overall health promotion for
      children.

PMID- 14653903
TI  - [Changes in the nutritional status of children in public day care facilities in
      the municipality of Sao Paulo, Brazil].
AB  - OBJECTIVE: To assess changes in the anthropometric characteristics of children
      receiving care in public day care facilities in the municipality of Sao Paulo,
      Brazil. METHODS: Using a sampling procedure, 21 day care centers and 849 children
      were selected for the study. The children in the study were to be weighed and
      measured at three points over a one-year period: in October of 1999, April of
      2000, and October of 2000. Of the 849 children selected, 821 of them were weighed
      and measured in October of 1999, and 420 of them were weighed and measured at all
      three points. The data in this paper refer to those 420 children. McNemar's chi
      square test was used to analyze any changes at the end of the year in the
      proportions of children who were malnourished or overweight. Two-way analysis of
      variance was used to compare the mean height-for-age, weight-for-age, and weight
      for-height z scores at the three observations. RESULTS: At the first observation,
      the prevalences found were: low height-for-age, 7.1%; low weight-for-age, 2.8%;
      low weight-for-height, 0.2%; and overweight, 5.7%. By the end of the year, the
      prevalence of low height-for-age had decreased to 3.1% (P = 0.007), of low weight
      for-age had decreased to 1.7% (P = 0.56), of low weight-for-height had increased
      to 0.5% (P = 0.99), and of overweight had increased to 6.9% (P = 0.33). Both
      malnutrition and overweight were more prevalent in children younger than 24
      months than they were among older children studied, at both the beginning and the
      end of the study period. The changes in the mean indices of height-for-age,
      weight-for-height, and weight-for-age over the one-year period were significantly
      positive, except for weight-for-height in children younger than 24 months.
      CONCLUSIONS: Our results indicate that receiving care in the public day care
      facilities had a positive impact on the nutritional status of the children over
      the one-year study period. However, the physical growth of the children in these
      day care centers should be monitored in order to prevent malnutrition from
      turning into another public health problem: excessive weight gain.

PMID- 14653904
TI  - Sources of exposure to and public health implications of organophosphate
      pesticides.
AB  - OBJECTIVE: To review the public health significance of organophosphate pesticide
      exposure in the United States of America. Since the situation of high
      organophosphate pesticide exposure and the concomitant health risks in the
      developing countries of the world is well known, this article seeks to highlight
      the public health significance of organophosphate exposure in the United States,
      where it is less common than in many other nations. Looking at the situation in
      the United States would serve to further emphasize the seriousness of
      organophosphate pesticide-related health issues in developing countries. METHODS:
      A search for journal articles on organophosphate pesticides and organophosphate
      exposure was done on the PubMed electronic bibliographic database system of the
      National Library of Medicine of the United States. To supplement that search,
      information on organophosphate toxicity, biological monitoring, and regulation of
      pesticides was obtained from other published articles, textbooks, and relevant
      Internet sites. RESULTS: Organophosphate pesticides are a group of chemicals that
      are mainly used in agriculture. Organophosphates inhibit the activity of both the
      cholinesterase (ChE) enzymes-red blood cell (RBC) ChE and serum ChE-resulting in
      the cholinergic features of organophosphate toxicity. A 50% reduction in serum
      ChE activity from the baseline is an indication of acute organophosphate
      toxicity. The RBC ChE activity, which is less rapidly depressed than the serum
      ChE activity, is a measure of chronic exposure to organophosphates. Exposures to
      organophosphates are broadly classified into two categories: occupational and
      environmental. Occupational exposures occur among agricultural workers (including
      migrant farmworkers), industrial workers, pest control exterminators, and other
      workers. Nonoccupational exposure affects a large segment of the general
      population in the United States. Residential exposures come from organophosphate
      pesticide use by exterminators and by household residents as well as from dietary
      and accidental exposures. Other environmental exposures occur in public places
      and areas close to farms, and exposures could also happen from organophosphate
      use in chemical warfare or terrorism. In the United States some organophosphate
      pesticides are restricted by the Environmental Protection Agency in order to
      protect humans, animals, and the environment. In addition, the Food Quality
      Protection Act regulates dietary exposure to pesticides, particularly for infants
      and children. CONCLUSIONS: Organophosphate pesticides continue to pose a risk to
      human health in the United States. Biological monitoring should be used to
      strictly regulate occupational exposures to organophosphates and thus protect the
      health and safety of workers. Among the public there should be an increased
      awareness of environmental exposure to organophosphates as well as of the threat
      of chemical warfare or terrorism.

PMID- 14653905
TI  - [Identifying barriers to food and nutrition policies in Colombia: a study using
      the Delphi method].
AB  - OBJECTIVE: To identify the most important barriers to the development and
      progress of Colombia's National Food and Nutrition Plan (NFNP) (which was enacted
      in 1996), from the viewpoint of food and nutrition plan planners, implementers,
      and academicians. METHODS: The research was carried out in two stages. The first
      stage consisted of a pilot study in 1998 based on individual interviews with 35
      key informants with knowledge of nutrition policies in Colombia, in order to
      identify possible groups of experts with experience in the development of the
      NFNP and also to confirm the relevance and feasibility of the research. The
      second stage consisted of a study using the Delphi method with 77 experts who
      identified the principal barriers that the NFNP was facing. In a second step in
      the Delphi process, 58 of the experts took the 10 barriers that had been
      mentioned most frequently in the first step and then ranked those barriers, using
      a point scale from 1 to 10. In order to analyze the individual responses overall
      and by the three groups (planners, implementers, and academicians), we calculated
      the mean, the median, and the standard deviation of the scores, and we then
      ranked the barriers according to their median point scores. When median values
      were the same, we then utilized the higher mean or the smaller standard
      deviation. We had meetings to discuss those results with the participating
      experts in order to assess the soundness of our interpretations, to explore the
      usefulness of the study, and to formulate recommendations. RESULTS: The five most
      important barriers identified were: (1) the poor linkage between the NFNP and
      other social and economic policies, and the lack of consistency with agriculture
      and foreign policies; (2) the lack of coordination between different sectors and
      administrative organizations in Colombia; (3) administrative corruption, which
      was made worse by violence and the lack of security; (4) inequity in the
      distribution of resources; and (5) the lack of continuity in the commitment by
      the different sectors that are involved. The experts who attended the sessions
      where the results were discussed said that their opinions had been interpreted
      correctly, and they also suggested possible ways to apply the study results and
      thus improve the operations of the NFNP. CONCLUSIONS: Food and nutrition policies
      in Colombia have faced various obstacles, both from outside sources and from
      within the policies themselves, which can limit their usefulness to society.
      There is need to create a coordinating body for the NFNP.

PMID- 14653906
TI  - Microbial contamination of disinfectants and antiseptics in four major hospitals
      in Trinidad.
AB  - OBJECTIVE: To assess the microbial contamination of disinfectants and antiseptics
      in major hospitals on the Caribbean island of Trinidad. METHODS: For this cross
      sectional study, disinfectants and antiseptics were sampled from the pharmacy
      departments, the pediatric/neonatal wards, and the surgical wards of four
      hospitals. The samples were cultured for aerobic bacteria on nutrient agar using
      the surface plating method. The antibiotic sensitivity of bacterial isolates was
      determined by the disk diffusion method, using 14 antimicrobial agents. We
      studied a total of 180 disinfectant/antiseptic samples: 60 of chlorhexidine
      gluconate (Hibitane), 60 of chlorhexidine gluconate and cetrimonium bromide
      (Savlon), and 60 of methylated spirit. RESULTS: Of the 180 samples studied, 11 of
      them (6.1%) were contaminated by aerobic bacteria. All bacteria isolated were
      Pseudomonas spp. Of the 11 contaminated samples, 6 of them (54.5%) occurred at
      the pharmacy level while 5 (45.5%) were from diluted pre-use or in-use samples in
      the pediatric/neonatal wards or the surgical wards. Chlorhexidine gluconate and
      cetrimonium bromide accounted for 9 of the 11 contaminated
      disinfectants/antiseptics (81.8%), and chlorhexidine gluconate accounted for the
      remaining 2 (18.2%). Only two of the four hospitals had contaminated
      disinfectant/antiseptic samples. All 24 isolates of Pseudomonas spp. tested were
      resistant to one or more of the 14 antimicrobial agents tested, with the
      prevalence of resistance to ciprofloxacin, norfloxacin, tobramycin, and
      gentamicin being 58.3%, 50.0%, 45.8%, and 41.7%, respectively. CONCLUSIONS: Our
      results show that contaminated disinfectants/antiseptics pose a health risk to
      patients, particularly in the pediatric and surgical wards. The high prevalence
      of resistance to antimicrobial agents exhibited by the Pseudomonas spp. that were
      isolated is of special therapeutic concern.

PMID- 14653907
TI  - [A comparison of three electrocardiogram coding systems for chronic Chagas'
      disease].
AB  - OBJECTIVE: To compare three electrocardiogram coding systems (Buenos Aires, New
      York Heart Association, and modified Minnesota) for use with Chagas' disease.
      METHODS: Between January 1976 and December 1978 persons older than 2 years of age
      living in the town of Agua Comprida, Minas Gerais, Brazil, underwent a patient
      history, physical examination, conventional electrocardiography, and serology for
      Chagas' disease. Those records were archived, and in 1999 from this sample, 100
      seropositive individuals were matched by sex and age with 100 seronegative
      controls. The electrocardiograms of these 200 patients were read using the three
      coding systems. Each system was assessed in terms of its gradient, that is, the
      difference between the number of abnormalities found in the electrocardiograms of
      individuals with and without Chagas' disease. RESULTS: The gradient was 7% for
      the New York Heart Association coding system, 15% for the modified Minnesota
      system, and 17% for the Buenos Aires one. The ability of the Buenos Aires method
      to detect electrocardiographic abnormalities was significantly greater in the
      group with Chagas' disease than in controls (P = 0.012), followed by the modified
      Minnesota system (P = 0.028) and the New York Heart Association system (P =
      0.31). The Buenos Aires method was also easier to use, in terms of both the
      analysis of electrocardiograms and queries to a database. CONCLUSIONS: Although
      the Buenos Aires method had advantages over the two other systems, some changes
      are still needed in it to make it more useful. It would be worth carrying out
      further studies to evaluate this method with the changes that we have suggested
      in this study.

PMID- 14653908
TI  - [Tuberculin reactivity among ninth-grade schoolchildren in the city of Havana,
      Cuba].
AB  - OBJECTIVE: To determine the proportion of 14-year-old schoolchildren in the city
      of Havana, Cuba, with a positive tuberculin skin test, as an indicator of the
      prevalence of tuberculosis infection among them. METHODS: Using single-stage
      cluster sampling, 1 936 Mantoux (tuberculin) tests were carried out with ninth
      grade students (cohort born in 1985) during the 1999- 2000 school year in 20
      basic high schools randomly selected in Havana. The tests were performed
      according to the standard technique recommended by the World Health Organization,
      and they were read after 72 hours. The percentage of skin tests that were
      positive and the average diameter of the indurations were calculated for the
      cohort overall and for the two genders. The means and the percentages were
      compared using the chi-square test, with 95% confidence intervals. The computer
      software used was Epi Info version 6.0. RESULTS: Of the tests read, 96% of them
      were negative (0-4 mm), 2.5% were doubtful (5-9 mm), and 1.5% were positive
      (>/=10 mm). The percentage of reactivity was 0.1% when a cutoff value of 15 mm
      was used. The mean diameter of the indurations was 0.41 mm. No statistically
      significant difference was found between the genders. CONCLUSIONS: In this study
      the proportion of schoolchildren with tuberculin reactivity, using an induration
      diameter cutoff point of 10 mm, was very low (1.5%), and it was much lower (0.1%)
      when a cutoff point of 15 mm was used. The skin reactions with an induration
      diameter of >/=10 mm could be the expression of a natural infection if one takes
      into account the low frequency of bacillary tuberculosis in Cuba and that there
      is an inverse relationship between the time elapsed from the BCG vaccination and
      the intensity of the response to tuberculin. Therefore, that would mean that in
      this case (l)the point (.)prevalence of tuberculosis infection in this group of
      schoolchildren wou d be 1.5% ResumenObjetivos. Determinar la proporcion de
      personas que reaccionan a la tuberculina como indicador de la prevalencia de
      infeccion tuberculosa en escolares de 14 anos de Ciudad de La Habana, Cuba.
      Metodos. Mediante un muestreo monoetapico por conglomerados se aplicaron 1 936
      pruebas de Mantoux (tuberculina) a estudiantes de noveno grado del curso escolar
      1999-2000 (cohorte de los nacidos en 1985) de 20 escuelas secundarias basicas
      seleccionadas aleatoriamente en Ciudad de La Habana, Cuba. Las pruebas se
      realizaron segun la tecnica estandar recomendada por la Organizacion Mundial de
      la Salud y se evaluaron a las 72 horas. Se calcularon los porcentajes de
      reactividad y el diametro medio de las induraciones cutaneas en la cohorte y
      segun el sexo. Las comparaciones de medias y porcentajes se realizaron mediante
      la prueba de ji al cuadrado con 95% de confiabilidad. Se uso el programa Epi Info
      v. 6.0. Resultados. Noventa y seis por ciento de las pruebas leidas fueron
      negativas (0-4 mm), 2,5% fueron dudosas (5-9 mm) y 1,5% resultaron positivas (
      >/= 10 mm). El porcentaje de reactividad disminuyo a 0,1% cuando se utilizo un
      valor de corte de 15 mm. El diametro medio de las induraciones fue de 0,41 mm y
      no se detecto ninguna diferencia estadisticamente significativa en funcion del
      sexo. Conclusiones. La proporcion de personas que reaccionaron a la tuberculina,
      usando como punto de corte un diametro de induracion cutanea de 10 mm, fue muy
      baja (1,5%) en este estudio y mucho mas baja (0,1%) cuando se utilizo 15 mm como
      punto de corte. Si se toma en cuenta la baja frecuencia de tuberculosis
      bacilifera en Cuba y que hay una relacion inversa entre el tiempo transcurrido
      desde la aplicacion de la vacuna a base del bacilo de Calmette-Guerin (BCG) y la
      intensidad de la respuesta a la tuberculina, las reacciones cutaneas con un
      diametro de induracion >/= 10 mm podrian ser la expresion de una infeccion
      natural, por lo que, en ese caso, la prevalencia puntual de infeccion tuberculosa
      en este grupo de escolares seria de 1,5%.

PMID- 14653913
TI  - Poor adherence to long-term treatment of chronic diseases is a worldwide problem.
      2003.

PMID- 14653915
TI  - Shrapnell's membrane in a mammal exposed to extreme pressure variations:
      morphological and radiological observations in the hooded seal.
AB  - The function of Shrapnell's membrane (pars flaccida; PF) in middle-ear mechanics
      is still an enigma, though numerous proposals have been put forward, e.g.
      protection of pars tensa, equalizing of middle-ear pressure, sound transmission,
      and the site of origin of otitis media. In this study the PF was studied in a
      mammal (the hooded seal) which exposes itself to extreme pressure differences
      (from 1 to 100 atmospheres) when diving. Formaldehyde-fixed temporal bones
      obtained from newborn, one-year-old, and adult seals (three of each) were
      cleansed and decalcified in 10 per cent EDTA. The lateral wall of the middle-ear
      cavity, including the whole tympanic membrane with its bony surroundings, was
      then excised and photodocumented. Thin sections were cut parallel with, and
      perpendicular to, the handle of the malleus, stained with haematoxylin-eosin,
      toluidine blue or Giemsa stain and examined under a light microscope. One seal
      head was subjected to high resolution computerized tomography (HRCT) before
      sectioning. The PF was observed to be a narrow fissure measuring a maximum of 0.8
      mm between processus brevis of the malleus and the notch of Rivinus in pars
      squamosa (pars tensa diameter 10-12 mm). It seems unlikely that the PF of the
      hooded seal participates in pressure equalization in the middle ear. The main
      function of the lateral wall of the attic, including the minimal PF, appears to
      be to protect the middle-ear ossicles and allow movement of the malleus.

PMID- 14653914
TI  - Use of laser, otoendoscopy and facial nerve monitoring in otological surgery:
      United Kingdom survey.
AB  - Newer surgical tools, which have been widely accepted as important adjuncts in
      otological surgery, include the laser, otoendoscopy and facial nerve monitoring.
      A confidential postal questionnaire survey was carried out to evaluate the usage
      of these newer techniques among the Consultant members of the British Association
      of Otorhinolaryngology-Head and Neck Surgery. Our study revealed that the usage
      of otoendoscopy, laser and/or facial nerve monitoring is not as widespread as
      might be thought among otological surgeons in the United Kingdom.

PMID- 14653916
TI  - Day-case myringoplasty: five years' experience.
AB  - A retrospective study of patients who underwent myringoplasty as a day-case
      procedure in two freestanding day-surgery units during a five-year period was
      carried out. Their case notes were identified and details including age, site and
      size of perforation, grade of surgeon, surgical approach, graft material, post
      operative dressings, overnight stay, complications, and outcome were noted and
      analysed. The total number of patients including both children and adults who had
      myringoplasty as a day case was 144. Of these, 125 patients with 143 procedures
      were included in this study. Their ages ranged from four to 74 years (mean = 31
      years). The perforation size was small in 40 cases, medium in 61 cases, and
      large/subtotal in 42 cases. The overnight stay rate was 2.7 per cent and this was
      for immediate post-operative problems such as nausea and bleeding from the wound.
      The readmission rate for post-operative complications was 2.1 per cent. The
      follow-up ranged from six months to five years (mean = 19 months). The success
      rate was 83.3 per cent and thresholds on pure tone audiometry improved in 69.2
      per cent of cases. The age of the patient, grade of the surgeon, and graft
      material did not influence the surgical outcome. There was no case of dead ear as
      a result of surgery. Myringoplasty can be safely performed in both adults and
      children as a day-case procedure with low overnight stay and readmission rates.
      Success rates are comparable to when the procedure is performed on an in-patient
      basis.

PMID- 14653917
TI  - Virtual reality modelling language: freely available cross-platform visualization
      technique for 3-D visualization of the inner ear.
AB  - This was a study of the use of virtual reality modelling language (VRML) for
      cross-platform interactive three-dimensional (3-D) visualization of high
      resolution magnetic resonance (MR) images of the inner ear in the assessment of
      cochlear implant candidates. A retrospective case review was made of cochlear
      implant candidates undergoing pre-operative high-resolution MR studies to
      determine their suitability for implantation. 3-D visualizations of MR scans of
      the inner ear structures were created using surface rendering and exported as
      portable VRML files. Case studies are presented to illustrate different points of
      interest. VRML reconstructions aided the interpretation of two-dimensional (2-D)
      source images in a variety of inner ear abnormalities. VRML is an internationally
      recognized standard for cross-platform 3-D visualization that creates a means of
      providing the implanting surgeon with a portable 3-D representation of the inner
      ear, aiding interpretation of the complex cross-sectional anatomy of these
      structures, and guiding selection of patients for implantation as well as
      implantation technique. The elucidation of the mechanisms behind inner ear
      malformations can also be aided by detailed imaging studies of the temporal bone,
      with VRML reconstructions providing an easily interpreted representation of
      deformities.

PMID- 14653919
TI  - Congenital internal auditory canal stenosis.
AB  - Congenital internal auditory canal stenosis is a rare cause of sensorineural
      hearing loss in children. A retrospective analysis including clinical
      manifestation and radiological findings was made for seven patients who were
      diagnosed with congenital internal auditory canal stenosis from 1996 to 2002.
      Chief presenting symptoms were hearing loss, facial nerve palsy, dizziness, and
      tinnitus. Hearing loss including deafness was found in five cases, vestibular
      function loss in four cases, and profound functional loss of facial nerve in two
      cases. In all cases, the diameter of the internal auditory canal was less than 2
      mm on high-resolution temporal bone computed tomography (CT) scan. Two cases
      revealed bilateral internal auditory canal stenosis, and others were unilaterally
      involved cases. Congenital internal auditory canal stenosis can be an important
      cause of sensorineural hearing loss, facial nerve palsy, and vestibular
      dysfunction. High resolution temporal bone CT scan and magnetic resonance (MR)
      imaging were important tools for diagnosis.

PMID- 14653918
TI  - Sudden presentation of immune-mediated inner ear disease: characterization and
      acceptance of a cochleovestibular dysfunction.
AB  - Since the McCabe report, growing indirect evidence has accumulated to indicate
      the implication of immune mechanisms in the pathogenesis of immune-mediated inner
      ear disease (IMIED). A clinical study of a group of patients affected by this
      condition was performed in order to characterize the immune group, based on a
      recently reported profile, and compared with the vascular, viral and idiopathic
      aetiologies of sudden deafness. Patients affected by immune-mediated inner-ear
      disease had the best and the earliest recovery rate of hearing (p = 0.0028 and p
      = 0.017, respectively). However, this group of patients also had the higher rate
      of recurrence (p = 0.034), supporting the typical clinical course of the
      autoimmune disorders. On the basis of the results the criteria used in the
      diagnosis of the sudden presentation of the immune-mediated inner ear disease
      could be accepted leading to the characterization of this condition. Likewise,
      the role of the supporting cells in the pathogenesis of the IMIED is discussed.

PMID- 14653920
TI  - Transapical extension in difficult cerebellopontine angle tumours: preliminary
      report.
AB  - Difficult cerebellopontine angle (CPA) tumours namely large/giant vestibular
      schwannomas, vestibular schwannomas with a significant anterior extension and
      meningiomas of the posterior surface of the petrous bone extending anterior to
      the internal auditory canal (IAC) have always posed a problem for the
      otoneurosurgeon. Modifications of the enlarged translabyrinthine approach (ETLA)
      specifically aimed at dealing with these tumours are not reported. The aim of
      this paper is to introduce the transapical extension of ETLA which involves
      increased circumferential drilling around the IAC beyond 270 degrees C. The
      extension allows enhanced surgical control over the tumour as well as the
      anterior aspect of the CPA including the prepontine cistern, the Vth and VIth
      cranial nerves. The extension is further classified into Type I and II depending
      upon the extent of drilling. Type I extension entails drilling around the IAC for
      300-320 degrees and is indicated for large/giant vestibular schwannomas (large
      vestibular schwannoma extrameatal diameter 3-39 cm, giant vestibular schwannoma
      extrameatal diameter >or=4 cm) and vestibular schwannomas with significant
      anterior extension. Type II extension involves complete drilling around the canal
      for 360 degrees and is indicated for meningiomas of the posterior surface of the
      petrous bone extending anterior to the IAC.

PMID- 14653922
TI  - What is the right size of the adenoid curette?
AB  - The use of an adenoid curette of appropriate size is recommended in operative
      textbooks for adequate adenoid removal and avoidance of potential injury to the
      eustachian tubes. The aim of this study is to calculate the right size of adenoid
      curettes to be used for children of different ages. The inter-tubal space (ITS)
      between the torus tubarius on both sides is the narrowest passage for adenoid
      curettage, and is identified in this study as the nasopharyngeal dimension to be
      considered in selecting the size of the adenoid curette. This prospective study
      is carried out on a series of 72 adenoidectomy cases aged from three to nine
      years at the Hearing and Speech Institute in Cairo, Egypt. The inter-tubal
      dimension (ITD) is measured for each child at the end of adenoidectomy and the
      results are recorded against the patient's age. The ITD ranged from 17-21 mm in
      our series with no significant difference between males and females. There is an
      increase in ITD with age with a sharp increase at ages five and seven years.
      Accordingly, the patients are divided into three age groups and recommendations
      for appropriate adenoid curette sizes ranging from 18 to 21 mm are given for each
      group.

PMID- 14653921
TI  - Role of endoscopic dacryocystorhinostomy in treating acquired lacrimal fistulae.
AB  - Acquired lacrimal fistula occurs in an improperly and inadequately treated
      lacrimal sac abscess. This study was done to evaluate the success of endoscopic
      dacryocystorhinostomy (EDCR) in treating such lacrimal fistula. A retrospective
      analysis of nine cases of acquired lacrimal fistulae in seven patients, treated
      by EDCR without any external surgery was carried out. Cessation of epiphora and
      closure of fistula were considered, successful outcomes. All the nine fistulae
      closed, and all patients were relieved of their epiphora within two weeks of
      surgery. It can be concluded that EDCR is effective for treating an acquired
      lacrimal fistula.

PMID- 14653923
TI  - Celon radiofrequency thermo-ablative palatoplasty for snoring - a pilot study.
AB  - A prospective non-randomized study was designed to investigate the effects of
      Celon radio-frequency thermo-ablation (RFTA) of the soft palate in patients with
      snoring/mild obstructive sleep apnoea. Ten patients, fulfilling various
      inclusion/exclusion criteria, underwent single operator sub-mucosal RFTA
      palatoplasty as an office procedure. Two separate procedures six weeks apart
      involved each patient receiving six distinct sub-mucosal lesions on each visit.
      Questionnaires including visual analogue scales (VAS) were used to evaluate post
      operative pain and subjective snoring (scored by patient/partner).
      Polysomnography (PSG) was performed pre-operation and three months following the
      second procedure. Using non-parametric statistical analysis, a significant
      reduction in VAS snoring was noted from initial levels to those scored at six and
      16 weeks in nine of 10 patients (p = 0.013 and p = 0.007 respectively). (Five of
      these nine showed a greater than 50 per cent reduction in score). Objectively,
      six of 10 patients had a reduction in the apnoea-hypopnea Index between the two
      PSGs, (four of these six showed a greater than 50 per cent reduction) however,
      this was not statistically significant. Subjective assessment of the PSG snoring
      signal by the senior author showed eight of 10 patients had either a reduced or
      much reduced signal at four months. VAS pain confirmed both procedures are well
      tolerated with minimal analgesia requirements. Minor complaints of transient mild
      palatal swelling, dry throat, catarrh and referred otalgia were noted and one
      patient developed mucosal ulceration following both procedures that healed within
      three weeks. Swallowing and speech were unaffected. These results confirm similar
      findings using the Somnus Unit, although the Celon device provides additional
      advantages including inherent safety in a bipolar electrode tip, auto-stop energy
      application and reduced procedure time.

PMID- 14653924
TI  - Diphtheria: the patch remains.
AB  - This study analysed the number of patients admitted with diphtheria to a teaching
      hospital in the state of Assam in India over a period of five years and compared
      the disease characteristics and management with outcomes and incidences of
      diphtheria reported in the literature. It was a retrospective analysis of data
      elicited from clinical records of patients admitted to hospital. A total of 101
      admissions were recorded during a five-year period between March 1997 to March
      2002, mostly with pharyngeal diphtheria (90 per cent). The majority of patients
      had no history of immunization (70 per cent). Significant presenting features
      were a tonsillar patch, sore throat, respiratory distress and fever. All patients
      were treated with anti-diphtheritic serum and intravenous antibiotics. Steroids
      were given to 81 per cent of patients and tracheostomy was carried out in 10 per
      cent of cases. The mortality was 16 per cent. Diphtheria of the respiratory tract
      remains a potentially fatal disease commonly presenting with membranous
      pharyngitis. Early diagnosis and treatment with anti-diphtheritic serum and
      antibiotics remain the cornerstone of treatment. Inadequate immunization cover is
      deemed responsible for the continued menace of diphtheria.

PMID- 14653925
TI  - South African survey on disinfection techniques for the flexible
      nasopharyngoscope.
AB  - This random survey was to determine the flexible nasopharyngoscope disinfection
      practice employed by South African otolaryngologists and to establish whether a
      breach in the disinfection process exists. The study also aimed to identify
      organisms most likely to be transmitted via endoscopy and to propose a protocol
      for the disinfection of the flexible nasopharyngoscope. A questionnaire regarding
      disinfection techniques used for the flexible nasopharyngoscope was sent to 90
      otolaryngologists in South Africa. All provinces were equally represented in the
      survey. Forty-five otolaryngologists out of a total of 90 participated in the
      study. Many of the otolaryngologists had no access to a flexible
      nasopharyngoscope and were therefore not included in the study. Fewer than 50 per
      cent of the 45 surgeons washed the instrument with soap/detergent and water after
      use. Only 42 per cent of surgeons used a FDA-approved disinfectant, 52 per cent
      of which immersed the scope for a shorter period than the recommended contact
      time. Of the 58 per cent using non-FDA-approved products, 33 per cent used only a
      70 per cent Isopropyl alcohol wipe, without immersion of the scope in
      disinfectant solution. The remaining 25 per cent used non-FDA-approved
      disinfectants either by wiping or limited immersion of the scope. Of the 45
      surgeons, 49 per cent used a different method of disinfection for high-risk
      patients. Strict guidelines have been proposed for the disinfection of this semi
      critical device by the Association of Professionals for Infection Control (APIC)
      and the Centers for Disease Control (CDC). These guidelines are currently not
      being followed by many South African otolaryngologists. There is therefore a real
      risk of transmitting infectious diseases, especially tuberculosis, via endoscopy.

PMID- 14653926
TI  - Conversion from a non-indwelling to a Provox2 indwelling voice prosthesis for
      speech rehabilitation: comparison of voice quality and patient preference.
AB  - This prospective study assessed the advantages and problems associated with
      converting a patient using an older generation non-indwelling voice prosthesis to
      a newer generation indwelling voice prosthesis, in this case the Provox2. The
      voice characteristics of each patient were measured using the old and then the
      new voice prosthesis. Technical aspects of the insertion of the indwelling
      prosthesis were noted. Each patient completed a questionnaire after a period of
      use with the indwelling prosthesis. Changing the prosthesis was simple and
      uncomplicated in 15 of 17 patients. Acoustic analysis showed improved parameters
      with the indwelling prosthesis, but no perceptual difference between the two
      prostheses. The questionnaire revealed that most patients preferred the
      indwelling prosthesis. Replacing a non-indwelling with an indwelling prosthesis
      is technically simple, leading to improvement in voice quality and patient
      satisfaction. It may be reasonable to offer this choice to patients currently
      using an older generation non-indwelling voice prosthesis.

PMID- 14653927
TI  - Outcomes of submandibular duct relocation: a 15-year experience.
AB  - Drooling is common in patients with neurological disability and a major factor
      affecting quality of life. Management of this problem is best carried out by a
      team approach using surgical and non-surgical methods. Submandibular duct
      relocation is a commonly performed procedure with low complication rate. This
      procedure has been carried out in 56 patients over the last 14 years at the
      Belfast City Hospital by the senior author. All the patients underwent
      physiotherapy for six months before they were selected for surgery. All the
      patients were over five years of age and most had severe neurological impairment.
      For the purposes of this study, all the patients were followed by a questionnaire
      regarding symptomatic improvement, parent satisfaction and complication rate. All
      case notes were also reviewed retrospectively. Parental satisfaction was high and
      drooling was significantly reduced in 49 cases. The main complication was ranula
      formation seen in five cases. The most significant area of parental concern was
      post-operative pain. It is important to counsel the parents regarding the post
      operative pain relief as well as failure rate of the procedure. It can be
      concluded that this procedure is a safe and highly successful procedure, which
      significantly improves the quality of life.

PMID- 14653928
TI  - Synchronous cystic teratomas of the craniofacial region.
AB  - A case of synchronous cystic teratomas presented with the complaints of a slow
      growing facial mass and forward protrusion of the right eye since birth. The
      patient was examined thoroughly and subjected to magnetic resonance imaging (MRI)
      scan. The MRI scan revealed the presence of two separate cysts in the right orbit
      and right temporal fossa. The patient was operated by a combined effort of
      ophthalmologists and otorhinolaryngologists. The cysts were excised and subjected
      to pathological examination. The histopathological survey revealed both the cysts
      to be mature cystic teratomas similar to each other. This coexistence of a
      primary temporal fossa teratoma with an orbital teratoma is the first of its kind
      and to the best of our knowledge has not been reported before.

PMID- 14653929
TI  - Intermittent self-nasal packing for intractable epistaxis in a patient with
      Ehlers-Danlos syndrome.
AB  - Intractable epistaxis is a difficult problem to manage, particularly in a case
      complicated by Ehlers-Danlos syndrome. This is the first report describing
      intermittent self-packing of the nasal cavities at home to reduce hospital
      admissions and control symptoms. Some of the potential problems and complications
      are highlighted.

PMID- 14653930
TI  - Stridor: unusual presentation of multiple myeloma.
AB  - We present a patient with multiple myeloma whose only presenting symptom was
      stridor caused by a subglottic stenosis. Biopsy suggested the presence of amyloid
      which prompted immunological investigations that showed hypogammaglobulinaemia
      and the presence of Bence Jones proteinuria at 0.93 g/24 hours. Further
      investigation demonstrated a 15 per cent plasma cell infiltrate into the bone
      marrow and a lytic lesion in the mid-shaft of the right femur. Chemotherapy and
      localized radiotherapy were commenced. This is a most unusual presentation of
      multiple myeloma and shows that immunoglobulin profiles should be properly
      investigated in such cases.

PMID- 14653931
TI  - Primary leiomyoma of the thyroid gland.
AB  - Primary thyroid leiomyomas are rare, and only four cases have been reported to
      date. This is a report of an additional case of primary thyroid leiomyoma in a 40
      year-old male who was admitted with a painless swelling in the right thyroid lobe
      and underwent subtotal thyroidectomy. The surgical specimen showed a well
      circumscribed, greyish-white solid nodule. Histologically, the tumour was
      composed of spindle cells with blunt-ended nuclei that were arranged with short
      intersecting bundles. Immunohistochemical staining revealed reactivity with
      smooth muscle actin, vimentin and desmin. Histopathologic and immunohistochemical
      assessments produced the diagnosis of thyroid leiomyoma. Although primary thyroid
      leiomyoma is rare, it should be considered in the differential diagnosis of a
      cold thyroid nodule.

PMID- 14653932
TI  - Ameloblastic carcinoma: case report and literature review.
AB  - Ameloblastic carcinoma is a rare malignant lesion with characteristic histologic
      features and behaviour that dictates a more aggressive surgical approach than
      that of a simple ameloblastoma. However, reliable evidence of its biologic
      activity is currently unavailable due to the scarcity of well-documented cases.
      It occurs primarily in the mandible in a wide range of age groups; no sex or race
      predilection has been noted. It may present as a cystic lesion with benign
      clinical features or as a large tissue mass with ulceration, significant bone
      resorption and tooth mobility. Because the lesion is usually found unexpectedly
      after an incisional biopsy or the removal of a cyst, a guide to differential
      diagnosis is not usually useful. The identifying features of ameloblastic
      carcinoma must be known and recognized by dental practitioners. Our understanding
      of the histologic features of ameloblastic carcinoma is somewhat vague. The
      tumour cells resemble the cells seen in ameloblastoma, but they show cytologic
      atypia. Moreover, they lack the characteristic arrangement seen in ameloblastoma.
      The clinical course of ameloblastic carcinoma is typically aggressive, with
      extensive local destruction. Direct extension of the tumour, lymph node
      involvement and metastasis to various sites (frequently the lung) have been
      reported. Wide local excision is the treatment of choice. Regional lymph node
      dissection should be considered and performed selectively. Radiotherapy and
      chemotherapy seem to be of limited value for the treatment of ameloblastic
      carcinomas. At the moment, there are too few reported cases to make a definite
      recommendation regarding treatment. Close periodic reassessment of the patient is
      mandatory.

PMID- 14653933
TI  - Nonsquamous cell malignant tumours of the oral cavity: an overview.
AB  - Many malignant tumours other than squamous cell carcinoma may present in the oral
      cavity. Melanomas of the oral cavity are usually pigmented, aggressive tumours
      associated with a poor prognosis. Neoplasms of the minor salivary glands have a
      greater tendency to be malignant than those of the major glands, and some exhibit
      a predilection for occurring in the mouth. Many types of connective tissue
      malignant tumours (sarcomas) may arise in the mouth, including soft-tissue
      cancers and lesions of hematologic cells such as lymphoma, whereas osteosarcoma
      is the most common malignancy of the hard tissues found in the mouth. Cancers
      from distant organs such as breast, lung and prostate may metastasize to the oral
      cavity. This paper presents a brief overview of nonsquamous cell oral cancers,
      with emphasis on those most likely to be encountered by the practising dentist.

PMID- 14653934
TI  - Oral and dental management related to radiation therapy for head and neck cancer.
AB  - The clinical management of squamous cell carcinoma of the head and neck causes
      oral sequelae that can compromise patients' quality of life and necessitate
      abandonment or reduction of optimal therapeutic regimens, which in turn reduces
      the odds of long-term survival. Such sequelae can be prevented or at least better
      managed if dental and medical health care providers work together. It is
      therefore essential that dentists have an understanding of cancer therapy and a
      sound working knowledge of the prevention and management options for the oral
      sequelae of cancer treatment. This paper offers the dental team an overview of
      the consequences associated with radiotherapy, as well as a systematic overview
      of preventing or managing acute and chronic conditions before and during
      radiotherapy. In addition, it reviews considerations for continued treatment
      needs during the patient"s lifetime.

PMID- 14653935
TI  - Are nicotine replacement strategies to facilitate smoking cessation safe?
AB  - Professional obligations to curb the prevalence of cigarette smoking reflect the
      importance of this preventable risk factor for innumerable diseases. These
      include chronic obstructive pulmonary disease and oral, lung and other cancers,
      although the morbidity and mortality rates for cerebrovascular disease (e.g.,
      ischemic strokes) and cardiovascular disease (e.g., ischemic myocardial
      infarction) tend to be greater. Various alternative nicotine sources (e.g.,
      transdermal nicotine patches, nicotine gum, nicotine nasal sprays) have been
      incorporated into smoking cessation programs. This review is intended to increase
      professional awareness of nicotine delivery systems available in Canada,
      including safety considerations. The pathogenic potential of nicotine, regardless
      of source, and the contraindications to the use of nicotine replacement therapies
      are discussed. However, the systemic nicotine load in individuals undergoing
      replacement therapy is generally lower than during active smoking. Nicotine is
      only one of many thousands of constituents of tobacco smoke. Furthermore,
      nicotine replacement is usually delivered over the short term (a matter of
      weeks). Therefore, nicotine replacement is recognized as a relatively safe and
      effective aid to smoking cessation.

PMID- 14653936
TI  - Histopathologic examination to confirm diagnosis of periapical lesions: a review.
AB  - Most periapical lesions are represented by inflammatory cysts, granulomas,
      abscesses or fibrous scars. These inflammatory conditions are often termed
      "endodontic lesions" because pulpal necrosis is the initiating event in their
      pathogenesis. Although rare, other clinically confusing periapical lesions have
      been extensively documented in numerous case reports and short case series. These
      lesions represent a wide range of pathosis, including various developmental
      cysts, infections, benign but locally aggressive lesions, and malignancies. The
      literature describing these lesions and the value of a histopathologic
      examination in diagnosis is reviewed.

PMID- 14653937
TI  - What is the critical pH and why does a tooth dissolve in acid?
AB  - This paper discusses the concept of critical pH for dissolution of enamel in oral
      fluids. The critical pH does not have a fixed value but rather is inversely
      proportional to the calcium and phosphate concentrations in the solution. The
      paper also discusses why teeth dissolve in acid, why remineralization of white
      spot caries lesions is possible and why remineralization of teeth eroded by acid
      is not possible.

PMID- 14653938
TI  - Have dentin adhesives become too hydrophilic?
AB  - This review discusses current trends in the development of dentin adhesives and
      the possibility that some classes of currently available adhesives are too
      hydrophilic. Manufacturers have reformulated dentin adhesives to make them more
      compatible for bonding to intrinsically moist, acid-etched dentin by adding 2
      hydroxyethyl methacrylate and other hydrophilic resin monomers. These 3-step
      adhesives work well but are more time consuming to use and more sensitive to
      technique than the newer, simplified adhesives. When primers are mixed with
      adhesives in 2-step single-bottle adhesives and self-etching primers, the
      adhesives are more permeable to water and hence absorb more water over time than
      previous generations of adhesives. The most recent single-step self-etching
      adhesives are even more hydrophilic and hence more permeable to water derived
      from the underlying bonded dentin. This permeability can lead to a wide variety
      of seemingly unrelated problems, including incompatibility of chemically or dual
      cured composites with simplified adhesives and expedited degradation of resin
      dentin bonds.

PMID- 14653939
TI  - Endodontic treatment of bilaterally occurring 4-rooted maxillary second molars:
      case report.
AB  - The presence of 4-rooted maxillary second molars has been described in only a
      limited number of case reports. Studies of anatomical features have demonstrated
      substantial variation in the number of roots and root canals in different teeth.
      The maxillary second molar usually has 1, 2, or 3 roots and generally 3 or 4 root
      canals. This case describes the presence of 4 roots occurring bilaterally in
      maxillary second molars in one patient.

PMID- 14653940
TI  - An index for the measurement of normal maximum mouth opening.
AB  - PURPOSE: The aim of this study was to evaluate the relationship between the width
      of 3 or 4 fingers of one hand and maximum mouth opening (MMO) in healthy
      subjects. METHODS: One hundred and forty dental students (age 21 to 42 years,
      mean 27.4 years) participated in the study. The ability of each subject to
      position 3 or 4 fingers, vertically aligned, between the upper and lower central
      incisors up to the first distal interphalangeal folds, was documented.
      Measurements of MMO and the width of 3 fingers (index, middle and ring fingers)
      and 4 fingers (index, middle, ring and little fingers) were recorded. RESULTS:
      All subjects were able to position 3 fingers (of both the right and left hands)
      between the upper and lower central incisors. Only 12 subjects were able to
      position 4 fingers (both right and left) in this way. There were no significant
      differences among the measurements of MMO (mean 48.8 mm), 3 fingers of the right
      hand (mean 47.3 mm) and 3 fingers of the left hand (mean 47.0 mm) (p > 0.05).
      However, MMO was significantly different from the width of 4 fingers of the right
      hand (mean 58.1 mm) and 4 fingers of the left hand (mean 57.5 mm) (p < 0.001).
      Moreover, there was a strong positive correlation between MMO and the 3-finger
      measurements (p < 0.0001). CONCLUSIONS: These findings strongly suggest that the
      ability to position 3 fingers in the mouth during dental examination is a
      convenient index for assessing normal MMO.

PMID- 14653941
TI  - Molsidomine and N-omega-nitro-L-arginine methyl ester inhibit implantation and
      apoptosis in mouse endometrium.
AB  - AIM: To investigate the possible effect of nitric oxide on receptivity and
      apoptosis of mouse endometrium and the possible pathway. METHODS: Female pregnant
      mice were treated with either molsidomine, a generator of nitric oxide (NO), or N
      omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. The
      pregnancy rates of each group were calculated; 3'-end-labeling was used to detect
      DNA fragmention of apoptotic cells; immunohistochemistry, in situ hybridization,
      and Western blot were applied respectively to estimate expression levels of
      Fas/FasL proteins and mRNA. RESULTS: The pregnancy rate in the drug treated group
      was reduced in a dose-dependent manner; apoptosis, Fas protein and mRNA levels in
      the endometrium of drug treated mice were correlatively decreased during the peri
      implantation period. CONCLUSION: The decreased pregnant rate in mice by abnormal
      levels of nitric oxide may be brought about by inhibiting the normally occurrence
      of apoptosis in the receptive endometrium.

PMID- 14653943
TI  - Survival and differentiation of transplanted neural stem cells in mice brain with
      MPTP-induced Parkinson disease.
AB  - AIM: To determine survival and differentiation of cultured neural stem cells
      (NSCs) into viable and functional neurons upon transplantation into mice brain of
      MPTP-induced Parkinson disease (PD). METHODS: Mouse model of PD was established
      with two subcutaneous (sc) injections of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP, 40 mg/kg) twice, 16 h apart. NSCs isolated from rat
      embryo midbrain were cultured in clonal density. After labeled with 5-bromo-2'
      deoxyuridine (BrdU), the NSCs were transplanted into the uni- or bi-lateral
      striatum of PD mouse. Tyrosine hydroxylase (TH) immunofluorescence was used to
      evaluate the toxicity of MPTP on the neural cells in the substantia nigra.
      Immunohistology and laser confocal microscope were used to detect the survival
      and differentiation of transplanted NSCs. RESULTS: The cultured NSCs generated
      neurospheres and differentiated into neuron and astrocyte. It indicated that the
      cultured NSCs were multipotent and self-renewal in vitro. TH-positive neural
      cells were significantly reduced in the substantia nigra. Immunohistology showed
      that the uni- or bi-lateral transplanted NSCs survived in the brain of PD model
      mouse. Laser confocal microscope indicated that some transplanted NSCs could
      properly differentiate into targeted TH-positive neural cells in vivo.
      CONCLUSION: The transplanted multipotent NSCs could survive and differentiate
      into functional dopamine neurons.

PMID- 14653942
TI  - Transport and uptake characteristics of a new derivative of berberine (CPU-86017)
      by human intestinal epithelial cell line: Caco-2.
AB  - AIM: The characteristics of transepithelial transport and uptake of CPU-86017 [[7
      (4-chlorbenzyl)-7,8,13,13alpha-tetrahydroberberine chloride, CTHB]], a new
      antiarrhythmia agent and a new derivative of berberine, were investigated on
      epithelial cell line (Caco-2) to further understand the absorption mechanism of
      berberine and its derivatives. METHODS: Caco-2 cell was used. RESULTS: 1) The
      permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017
      was approximately 5 times higher than that from BL-to-AP transport. The effects
      of a P-glycoprotein (P-gp) inhibitor-cyclosporin A, some surfactants, and lower
      pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine
      A at 7.5 mg/L had no effect on the transepithelial electrical resistance (TEER);
      an about 4-fold enhancement on the transepithlial transport of CPU-86017 was
      observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium
      dodecyl sulfate) at 100 micromol/L and low pH (pH=6.0) induced a reversible
      decrease of TEER; enhancements of the transepithelial transport of CPU-86017 were
      also observed with some surfactants; 2) In the process of uptake of CPU-86017,
      the initial uptake rates of CPU-86017 were saturable with a Vmax of (250+/-39)
      microg/min/g (protein) and Km of (0.90+/-0.12) mmol/L. This process was enhanced
      by cyclosporine A (7.5 mg/L) with a Vmax of (588+/-49) microg/min/g (protein) and
      Km (0.42+/-0.08) mmol/L. CONCLUSION: Some surfactants and P-gp inhibitors can be
      considered as enhancers of its transepithelial transport and uptake.

PMID- 14653944
TI  - CMV-hFasL transgenic mice are sensitive to low doses of streptozotocin-induced
      type I diabetes mellitus.
AB  - AIM: To investigate the role of Fas-FasL pathway in the pathogenesis of
      streptozotocin (STZ)-induced type I diabetes mellitus. METHODS: Low dose
      injections of STZ were used to induce type I diabetes mellitus in the CMV-hFasL
      transgenic mice. Blood glucose concentration was measured with Glucotrand Plus
      blood glucose test strips. Expression of hFasL was detected by RT-PCR and Western
      blotting. The severity of insulitis was determined by histological examination.
      Expressions of IL-1beta and TNF-alpha mRNA in the pancreas were detected by semi
      quantitative RT-PCR analysis. Fas expression in apoptotic RIN-5F cells was also
      confirmed by RT-PCR in vitro. RESULTS: hFasL was expressed in the islets of CMV
      hFasL transgenic mice. The transgenic mice were sensitive to diabetic induction
      than the control WT mice. IL-1beta and TNF-alpha expressions in the pancreas of
      CMV-hFasL transgenic mice were far more than that in WT mice. We also found STZ
      and IL-1beta could both induce higher expression of Fas in RIN-5F. The combining
      of Fas-FasL could lead to the apoptosis of beta cells in the CMV-hFasL transgenic
      mice. CONCLUSION: Fas-FasL interaction plays a significant role in the pathogenic
      mechanism of type I diabetes mellitus.

PMID- 14653945
TI  - Induction of CRMP-4 in striatum of adult rat after transient brain ischemia.
AB  - AIM: To study the expression of collapsing response mediated protein-4 (CRMP-4)
      and nestin in the ischemic adult rat brain following transient brain ischemia.
      METHODS: Brain ischemia was induced by transient left middle cerebral artery
      occlusion (MCAO) for 60 min in adult rats. The expression of CRMP-4, nestin and
      bromodeoxyuridine (BrdU) was analyzed by immunohistochemical method. The co
      localization of CRMP-4 and nestin or BrdU was analyzed by double staining
      combined with confocal laser scanning microscopy. RESULTS: CRMP-4, a marker of
      immature neuron, could be expressed in the ipsilateral striatum and cerebral
      cortex at 1st and 2nd week after the ischemia-reperfusion; nestin, a marker of
      neural stem cell, occurred in above regions from several hours to 2 weeks. CRMP-4
      costained with nestin and with BrdU incorporation. CONCLUSION: Neural stem cells
      may present in the striatum and cerebral cortex of adult rat and can be triggered
      to differentiate into newborn neuron there by ischemic brain trauma.

PMID- 14653946
TI  - Puerarin blocks Na+ current in rat ventricular myocytes.
AB  - AIM: To study the effect of puerarin (Pue) on Na+ channel in rat ventricular
      myocytes. METHODS: Whole-cell patch-clamp technique was applied on isolated
      cardiomyocytes from rats. RESULTS: Pue inhibited cardiac INa in a positive rate
      dependent and dose-dependent manner, with an IC(50) of 349 micromol/L. The
      kinetics of blockage of cardiac sodium channel by Pue resembled the ClassIa/Ic of
      antiarrhythmic agents. Pue 300 micromol/L did not alter the shape of the I-V
      curve of INa, but markedly shifted the steady-state inactivation curve of INa
      towards more negative potential by 15.9 mV, and postponed the recovery of INa
      inactivation state from (21.9+/-1.6) ms to (54.4+/-3.4) ms (P<0.01). It
      demonstrated that the steady state of inactivation was affected by Pue
      significantly. CONCLUSION: Pue protected ventricular myocytes against cardiac
      damage and arrhythmias by inhibiting recovery from inactivation of cardiac Na+
      channels.

PMID- 14653947
TI  - Electrophysiological responses to imidazoline/alpha2-receptor agonists in rabbit
      sinoatrial node pacemaker cells.
AB  - AIM: To compare the effects of moxonidine (Mox), clonidine (Clo), agmatine (Agm),
      and xylazine (Xyl) on action potentials (AP) of the rabbit sinoatrial node (SAN)
      pacemaker cells and investigate the contribution of alpha-adrenoceptors to the
      cardiac electrophysiologic responses induced by the agonists. METHODS:
      Intracellular microelectrode technique was used to record AP in the rabbit SAN
      pacemaker cells. Vasoconstrictive responses to norepinephrine (NE), Mox, Clo, Agm
      and Xyl were observed in the thoracic aorta and ear vein isolated from rabbits.
      RESULTS: (1) In the rabbit thoracic aorta, a rank order of potency producing
      vasoconstrictive responses was NE>Clo>Mox; and a rank order of potency in ear
      vein was Clo>NE>Xyl=Mox. Agm did not produce any vascular responses in both
      preparations, and Xyl did not produce vascular responses in the thoracic aorta.
      (2) Mox, Clo, Xyl, and Agm concentration-dependently decreased the rate of
      pacemaker firing (RPF), and prolonged APD50 and APD90 in the rabbit SAN pacemaker
      cells. The rank order of decreasing RPF or prolonging APD was Clo>Xyl=Mox. (3)
      Most effects of Clo were partially inhibited by yohimbine, but those of Xyl and
      all the effects of Agm on the AP in SAN pacemaker cells were not affected by the
      treatment with yohimbine. (4) In the presence of propranolol 1 micromol/L,
      phenylephrine did not cause any effects on AP in the rabbit SAN pacemaker cells.
      CONCLUSION: Like Mox, Clo changes AP of the rabbit SAN pacemaker cells via alpha2
      adrenoceptors partially, but the effects of Xyl and Agm on the AP are almost not
      related to alpha2-adrenoceptors. Moreover, there are no obviously functional
      alpha1-adrenoceptors in the rabbit SAN pacemaker cells.

PMID- 14653948
TI  - Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular
      myocytes.
AB  - AIM: To study the effects of tumor necrosis factor-alpha (TNF-alpha) on calcium
      movement in rat ventricular myocytes. METHODS: Intracellular free Ca2+
      concentration was measured with calcium fluorescent probe Fluo-3/AM and laser
      confocal microscope. L-type calcium current (ICa,L) was recorded with the whole
      cell configuration of the patch-clamp techniques. RESULTS: At 2, 20 and 200
      microg/L, TNF-alpha was found to increase intracellular free Ca2+ concentration
      in a dose-dependent manner illustrated by the increment of calcium fluorescence
      density with laser confocal microscope. Nicardipine 0.5 micromol/L slightly
      attenuated TNF-alpha-induced response. When the cardiac myocytes were exposed to
      caffeine (100 mmol/L) for 30 min, TNF-alpha failed to induce any change of
      intracellular free calcium. However, it was found that TNF-alpha inhibited
      I(Ca,L) in whole-cell patch-clamp experiments. At 2, 20, and 200 microg/L, TNF
      alpha decreased peak I(Ca,L) by 3.9 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.9 pA/pF+/-0.2
      pA/pF, n=9, P>0.05), 15.7 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.3 pA/pF+/-0.3 pA/pF,
      n=9, P<0.05) and 19.6 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.1 pA/pF+/-0.4 pA/pF, n=9,
      P<0.01), respectively. It shifted the steady-state inactivation curve of I(Ca,L)
      to the left (V1/2 shifted from -28.7 mV+/-0.3 mV to -37.8 mV+/-1.4 mV, n=7,
      P<0.05), while it took no effects on steady-state activation and recovery from
      inactivation. CONCLUSION: TNF-alpha inhibited I(Ca,L) in rat ventricular
      myocytes, while increasing the intercellular free Ca2+ level due to the release
      of Ca2+ from intracellular stores.

PMID- 14653949
TI  - Inhibitory effect of quercetin on proliferation of human microvascular
      endothelial cells in vitro.
AB  - AIM: To investigate the role of quercetin (Que) in the proliferation of cultured
      human skin microvascular endothelial cells (MVEC). METHODS: Cell count and
      [methyl-3H]thymidine ([3H]TdR) uptake assay were used to measure the effect of
      Que in the proliferation of cultured MVEC. Cytotoxicity of Que on MVEC was also
      evaluated by 51Cr release assay. RESULTS: When MVEC were treated with Que, the
      proliferation was significantly inhibited in a time-course and dose-dependent
      manner. Que 5 micromol/L did not inhibit the proliferation of MVEC. When the
      concentration of Que increased to 20, 40, 80, and 160 micromol/L, the cell
      numbers per well were decreased and the inhibition rate was 12.2 %, 23.5 %, 35.3
      %, and 54.1 % respectively with IC50 of 138 micromol/L. The inhibitory rate of
      [3H]-TdR uptake was 18.7 %, 34.4 %, 48.9 %, and 62.5 % respectively (IC(50)=87.5
      micromol/L). (51)Cr release assay showed that Que 160 micromol/L incubated with
      MVEC from 1 to 16 h had no clear cytotoxicity compared with control group.
      CONCLUSION: Que greatly inhibited the proliferation of cultured human MVEC in
      vitro. This effect may not be related to the cytotoxicity of Que on MVEC.

PMID- 14653950
TI  - Down-regulation of survivin expression reversed multidrug resistance in
      adriamycin-resistant HL-60/ADR cell line.
AB  - AIM: To investigate the ability of an antisense RNA eukaryotic expression plasmid
      pcDNA3.1/survivin in down-regulating the expression level of survivin mRNA and
      survivin protein and reversed multidrug resistance (MDR) in adriamycin-resistant
      HL-60/ADR cell line. METHODS: The expression of survivin mRNA was measured by RT
      PCR and the expression of survivin protein was measured by Western blot. Caspase
      3 activity was determined by Phar Mingen colorimetric assay kit. Apoptosis was
      assessed by flow cytometry. The chemosensitivity of HL-60/ADR cells to adriamycin
      (ADR) was measured by MTT assay. RESULTS: pcDNA3.1/survivin down-regulated the
      expression level of survivin mRNA and survivin protein obviously, and induced
      apoptosis of HL-60/ADR cells in a time-dependent manner during 12-48 h. After
      transient transfection with pcDNA3.1/survivin for 48 h, survivin mRNA decreased
      by 67 %, survivin protein decreased by 57 %, caspase-3 activity increased 4.37
      times, and the apoptosis rate increased by 4.41 % compared with control. Compared
      with ADR alone, pcDNA3.1/survivin significantly reversed MDR in HL-60/ADR cells,
      the chemosensitivity of HL-60/ADR cells to ADR was increased to 5.36 folds.
      CONCLUSION: pcDNA3.1/survivin down-regulated the expression level of survivin
      mRNA and survivin protein obviously, the threshold of apoptosis was decreased and
      MDR was reversed.

PMID- 14653951
TI  - Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on
      transient global cerebral ischemia in rats.
AB  - AIM: To determine whether ONO-1078 [pranlukast, 4-oxo-8-[p-(4
      phenylbutyloxy)benzoyl-amono]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate], a
      potent leukotriene receptor antagonist, possesses a neuroprotective effect on
      global cerebral ischemia in rats, and to explore its possible mechanism of
      action. METHODS: Transient global cerebral ischemia was induced by four-vessel
      occlusion for 10 min and followed by 72-h reperfusion. ONO-1078 (0.03-0.3 mg/kg)
      and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one, a neuroprotective
      agent) 10 mg/kg were ip injected 30 min before ischemia and 1 h after
      reperfusion, and once a day afterward. Neurological outcome was evaluated before
      ischemia and 24, 48, 72 h after reperfusion. Neuron density, the expressions of N
      methyl-D-aspartate (NMDA) receptor subunit proteins (NR1, NR2A, NA2B) and
      vascular cell adhesion molecule 1 (VCAM-1) in the cerebral cortex and hippocampus
      were measured at 72 h after reperfusion. RESULTS: ONO-1078 (0.1, 0.3 mg/kg) and
      edaravone (10 mg/kg) improved ischemia-induced neurological deficiency and
      reduced neuron death. ONO-1078 (0.1, 0.3 mg/kg) significantly inhibited the
      enhanced expression of NMDA receptor subunit protein NR2A in the cortex and VCAM
      1 in the hippocampus of ischemic rats. CONCLUSION: ONO-1078 possesses a
      neuroprotective effect on global cerebral ischemia in rats, and its mechanism may
      be partly related to the inhibition of the upregulation of NR2A and VCAM-1 in
      different regions of the brain.

PMID- 14653952
TI  - Blockade of paeoniflorin on sodium current in mouse hippocampal CA1 neurons.
AB  - AIM: To study the blockade of paeoniflorin (Pae) on I(Na) in the acutely isolated
      hippocampus neurons of mice. METHODS: The whole-cell patch clamp technique was
      used. RESULTS: Pae inhibited I(Na) in frequency-dependent and concentration
      dependent manners, with an IC50 of 271 micromol/L. Pae 0.3 mmol/L shifted the
      activation potential of the maximal I(Na) from -40 mV to -30 mV, shifted the
      steady-state activation and inactivation curves toward more positive and negative
      potentials by 10.8 mV, and 18.2 mV, respectively, and postponed the recovery of
      I(Na) inactivation state from (4.2+/-0.7) ms to (9.8+/-1.2) ms. CONCLUSION: Pae
      inhibited I(Na) in mouse hippocampus neurons.

PMID- 14653953
TI  - Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP- response
      element binding protein in cultured rat hippocampal neurons.
AB  - AIM: To define the effects and signal pathways of ohmefentanyl stereoisomers [(-)
      cis-(3R,4S,2'R) OMF (F9202), (+)-cis-(3R,4S,2'S) OMF (F9204), and (-)-cis
      (3S,4S,2'R) OMF (F9203)] on the phosphorylation of cAMP-response element binding
      protein (CREB) in cultured rat hippocampal neurons. METHODS: The effects of the
      three OMF stereoisomers and morphine (Mor) on cAMP accumulation and CREB
      phosphorylation were monitored by radioimmunoassay and Western blot analysis,
      respectively. RESULTS: The three OMF stereoisomers and Mor could all partially
      inhibit forskolin-stimulated (25 micromol/L, 15 min) cAMP accumulation in a dose
      dependent manner and this effect could be reversed by naloxone. F9202, F9204, and
      Mor could significantly increase CREB phosphorylation from 2.88 to 3.59 folds
      over control levels after 30-min exposure. This effect was reversed by naloxone,
      but F9203 failed to increase CREB phosphorylation. KN-62 and staurosporine
      significantly blocked the opioids- induced CREB phosphorylation, while H-89 and
      PD 98059 had no effect on the actions. CONCLUSION: Mor, F9202, and F9204, which
      could induce psychological dependence affected via the micro-opioid receptor,
      stimulated intracellular signal pathways involving Ca2+/calmodulin-dependent
      protein kinases (CCDPK) and protein kinase C (PKC) pathways, which in turn
      initiated CREB phosphorylation. F9203, which could not induce dependence, had no
      effect on CREB phosphorylation in hippocampal neurons. The increased CREB
      phosphorylation in hippocampal neurons may play a role in opioids dependence.

PMID- 14653954
TI  - Involvement of CDK4, pRB, and E2F1 in ginsenoside Rg1 protecting rat cortical
      neurons from beta-amyloid-induced apoptosis.
AB  - AIM: To explore the possible mechanism of beta-amyloid (Abeta)-induced apoptosis
      in rat cortical neurons and the protective effect of ginsenoside Rg1. METHODS: AO
      EB staining was used to quantify the apoptotic cells. DNA fragmentation was
      observed by gel electrophoresis. The levels of cyclin-dependent kinases-4 (CDK4)
      and phosphorylated pRB were detected by Western blot. RT-PCR was used to examine
      the expression of E2F1 mRNA. RESULTS: Treatment with Abeta1-40 at the
      concentration of 20, 40, 80 mg/L for 48 h induced rat cortical neuron apoptosis
      from 12.5 %+/-1.5 % (control) to 22.3 %+/-1.4 %, 38.8 %+/-1.3 %, 36.7 %+/-1.4 %,
      respectively. Pretreatment with Rg1 at the dose of 0.5, 1, 2, 4, 8, 16 micromol/L
      for 24 h, then treatment with Abeta1-40 40 mg/L for 24 h, the percentage of
      apoptotic neurons decreased from 38.8 %+/-1.3 % to 14.5 %+/-1.3 %, 13.3 %+/-1.0
      %, 11.6 %+/-0.29 %, 11.8 %+/-1.0 %, 6.2 %+/-0.8 %, 5.8 %+/-0.8 %, respectively.
      After treatment with Abeta1-40 40 mg/L for 24 h, there were transient increases
      in CDK4 and phosphorylated pRB protein level, as well as the expression of E2F1
      mRNA. However, the above levels decreased markedly after pretreatment with Rg1 8
      micromol/L for 24 h. CONCLUSION: Ginsenoside Rg1 attenuated Abeta1-40-induced
      apoptosis in rat cortical neurons via inhibiting the activity of CDK4, decreasing
      the phosphorylation of pRB and downregulating the expression of E2F1 mRNA.

PMID- 14653955
TI  - Gender-related differences in pharmacokinetics of enantiomers of trans-tramadol
      and its active metabolite, trans-O-demethyltramadol, in rats.
AB  - AIM: To compare the pharmacokinetics of the enantiomers of trans-tramadol (trans
      T) and its active metabolite, trans-O-demethyltramadol (M1), in male and female
      rats. METHODS: Following a single oral dose of 10 mg/kg trans-T hydrochloride to
      rats, (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 in plasma were determined by a
      high performance capillary electrophoresis method. RESULTS: The females showed
      higher plasma concentrations of (+)-trans-T, (-)-trans-T, and (+)-M1 than the
      males. The enantiomers of trans-T were absorbed and eliminated more slowly in the
      females than in the males. (+)-M1 was eliminated more slowly in the females than
      in the males. All pharmacokinetic parameters but Tmax of the two enantiomers of
      trans-T were significantly different in both sex rats. The (+)/(-)-enantiomeric
      ratios of the pharmacokinetic parameters for trans-T in the males were similar to
      those in the females. The values of Cmax, AUC(0-infinity) of the two enantiomers
      of M1 were significantly different in both sex rats. The (+)/(-)-enantiomeric
      ratios of Cmax, AUC(0-infinity) for M1 were lower than 1 in the males, larger
      than 1 in the females. CONCLUSIONS: Systemic exposure of (+)-trans-T, (-)-trans
      T, and (+)-M1 was higher in female rats than in male rats. The stereoselectivity
      in pharmacokinetics of trans-T was similar, and that of M1 was different in male
      and female rats.

PMID- 14653957
TI  - Influence of CYP2D6*10B genotype on pharmacokinetics of propafenone enantiomers
      in Chinese subjects.
AB  - AIM: To study the relationship between genotype of CYP2D6*10B and
      pharmacokinetics of propafenone enantiomers. METHODS: Genotype of 17 healthy
      Chinese HAN subjects was determined by an allele specific amplification method.
      The blood samples (0-15 h) of the subjects were taken after oral administration
      of a single dose (400 mg) of propafenone hydrochloride. Concentrations of
      propafenone enantiomers in plasma were measured by a reverse-phase HPLC with
      precolumn derivatization. RESULTS: Seventeen subjects characterized for
      CYP2D6*10B genotype included (*1/*1) (n=4), (*1/*10) (n=5) and (*10/*10) (n=8).
      The metabolic ratios (lg MR) of the three genotypes were -2.68+/-0.23, -2.2+/
      0.7, and -1.1+/-0.5, respectively. The AUC of the three groups were (1534+/-334),
      (1891+/-793), (3171+/-1075) microg.h.L(-1) for S-enantiomer and (1136+/-345),
      (1467+/-817), (2277+/-745) microg.h.L(-1) for R-enantiomer, respectively. The AUC
      of propafenone enantiomers in *10/*10 is about 1.5-2 times of that of *1/*10
      group or *1/*1 group, and the CL of both enantiomers in *10/*10 is only half of
      that of *1/*10 group or *1/*1 group (P<0.05). CONCLUSION: CYP2D6*10B alleles
      induce the declined activity of CYP2D6 and impair the metabolism of propafenone.

PMID- 14653956
TI  - Facilitating effect of histamine on spatial memory deficits induced by
      dizocilpine as evaluated by 8-arm radial maze in SD rats.
AB  - AIM: To investigate whether or not histamine is involved in spatial memory
      deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of
      rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial
      memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801
      (0.3 microg/site) impaired working memory and reference memory in rats. Both
      histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine
      (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801.
      On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was
      completely antagonized by alpha-fluoromethylhistidine (alpha-FMH, 5 microg/site,
      ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1
      antagonist pyrilamine (1 microg/site, ih), but not by H2-antagonist cimetidine,
      even at a high dose (2.5 microg/site, ih). CONCLUSION: The hippocampal histamine
      plays an important role in the ameliorating effect on MK-801-induced spatial
      memory deficits, and its action is mediated through postsynaptic H1-receptor.

PMID- 14653959
TI  - Acute lung injury in 2003.
AB  - During the past several decades, clinical investigators world-wide have continued
      to study the causes, pathophysiology, and treatment strategies for acute lung
      injury (ALI). This syndrome, which is characterized by nonhydrostatic pulmonary
      edema and hypoxemia associated with a variety of etiologies, is slowly becoming
      better understood as a result of these efforts.

PMID- 14653958
TI  - Increase of beta1-adrenergic receptor gene expression induced by nicotine in
      hippocampal slice of rat.
AB  - AIM: To investigate the effect of nicotine on beta1-adrenergic receptor (beta1
      AR) in the hippocampal slice of rat. METHODS: Hippocampal slices (400 microm
      thick) were incubated in artificial cerebrospinal fluid (ACSF) previously
      saturated with 95 % O2 and 5 % CO2 at 28 degree for 120 min, and then incubated
      with nicotine 10 micromol/L for 30, 60, 90, and 120 min. mRNA of the beta1
      adrenergic receptor was examined with semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR), and the protein level was measured by Western
      blot and RIA. RESULTS: The mRNA gene expression and the protein level of beta1
      adrenergic receptor in hippocampal slices were increased after nicotine
      treatment. The peak of protein occurred later but higher than that of mRNA level.
      CONCLUSION: Both expression of beta1- adrenergic receptor gene transcription and
      post-transcriptional protein level in rat hippocampus were altered by nicotine.

PMID- 14653960
TI  - Interaction of secreted phospholipase A2 and pulmonary surfactant and its
      pathophysiological relevance in acute respiratory distress syndrome.

PMID- 14653961
TI  - Interaction of vascular endothelial cells with leukocytes, platelets and cancer
      cells in inflammation, thrombosis and cancer growth and metastasis.
AB  - Adhesion and migration of mammalian cells are of crucial importance in a number
      of biological events, such as fertilization, embryogenesis, pattern, tissue and
      organ formation, and in a variety of physiological and pathological processes,
      including lymphocyte trafficking, leukocyte recruitment, hemostasis, wound
      healing, tumor angiogenesis and cancer metastasis. All these cellular
      interactions are precisely regulated by temporal and spatial presentation of
      various cell adhesion molecules and chemotactical molecules displaying
      appropriate specificity and affinity for proper development and functioning of
      the organism. My research is focused on the structures and functions of vascular
      endothelial cells. I am especially interested in the biological roles of
      endothelial cells in mediating adhesion and migration of leukocytes, platelets
      and cancer cells as well as their involvements in inflammation, thrombosis,
      cancer growth and meta-stasis.

PMID- 14653962
TI  - Surfactant phospholipids and proteins in lung defence.

PMID- 14653963
TI  - Open lung in ARDS.
AB  - Every year, millions of patients worldwide receive ventilator support during
      surgery. Mechanical ventilation has become an important therapy in the treatment
      of patients with impaired pulmonary function and particularly in patients
      suffering from adult respiratory distress syndrome (ARDS). ARDS is caused by
      multiple factors and is characterized by respiratory dysfunction including
      hypoxemia and decreased lung compliance. It is known that the decrease in lung
      distensibility is due to a disturbed surfactant system with an elevated surface
      tension. This increase in surface tension leads to an increase in forces acting
      at the air-liquid interface, resulting finally in end-expiratory collapse,
      atelectasis, an increase in right-to-left shunt and a decrease in paO2.

PMID- 14653965
TI  - Reassessment of inhaled nitric oxide in acute lung injury.

PMID- 14653964
TI  - Molecular diagnostics of atypical pneumonia.
AB  - The emergence of nucleic acid-based molecular techniques has significantly
      enhanced laboratory diagnosis and monitoring of atypical pneumonia. These
      techniques have not only provided rapid and sensitive detection of fastidious
      microbial organisms but have also played critical roles in identifying and
      characterizing emerging pathogens that cause atypical pneumonia. Other benefits
      that molecular techniques can bring to the field include organism
      differentiation, quantitation, typing, and antibiotic resistance profiles.
      Gradually becoming standardized and widely available, the future will see some
      promising molecular methods become a mainstay in clinical laboratories for
      recognition and diagnosis of atypical pneumonia pathogens.

PMID- 14653966
TI  - Regulation of activity of nuclear factor-kappaB and activator protein-1 by nitric
      oxide, surfactant and glucocorticoids in alveolar macrophages from piglets with
      acute lung injury.
AB  - AIM: To investigate whether acute lung injury (ALI) in ventilated piglets with
      bacterial infection affects NF-kappaB and AP-1 expression in alveolar macrophages
      (AM) and whether nitric oxide (NO), surfactant (Surf), glucocorticoids (GC)
      affect NF-kappaB and AP-1 activation in AM in vivo and in vitro. METHODS: The
      animals were intraperitoneally injected Escherichia coli, which caused ALI.
      Nuclear extracts of AM were analyzed by electrophoretic mobility shift assay
      (EMSA) for the nuclear factor-kappa B (NF-kappaB) and activation protein-1 (AP-1)
      expression. Detection of IkappaB-alpha protein was from cytoplasmic extract by
      Western blotting. Immunocytochemistry staining was used for intracellular
      location of p65 subunits of NF-kappaB. RESULTS: In ex vivo experiments,
      strikingly higher expression of NF-kappaB and AP-1 by EMSA was found 6 h after
      bacterial injection in contrast to the Normal group. In the NO, SNO, and GC
      groups, markedly attenuated NF-kappaB and AP-1 activation was observed. The NF
      kappaB and AP-1 activation in Surf group showed lower levels of the expression.
      Immunoblotting of AM cytoplasmic extract showed low expression of IkappaB
      alphaprotein in the Control and Surf groups. The stronger expression was observed
      in the NO, GC, and SNO groups. AM of the Control and Surf groups showed intense
      nuclear staining, with decreased nuclear staining in the NO, GC and SNO groups.
      In in vitro experiment, it caused a significant increase in NF-kappaB and AP-1
      activity in AM 1 h after exposure to lipopolysaccharides (LPS). In AM treated by
      LPS+SNP and LPS+GC, all showed decrease of DNA binding activity of NF-kappaB and
      AP-1 compared to those exposed to LPS+Surf. Immunoblotting of AM cytoplasmic
      extract showed that LPS stimulation of AM resulted in the low expression of
      IkappaB-alpha protein, which was not observed in the presence of SNP and
      methylprednisolone. However, the surfactant did not show such effect. LPS+Surf
      exposed AM had intense nuclear staining, whereas decreased nuclear staining in
      the LPS+NO and LPS+GC-treated cultures was found, confirming a decrease in NF
      kappaB activity. CONCLUSION: Activation of NF-kappaB was found in AM of
      ventilated piglets with bacterial ALI. NO and GS could prevent NF-kappaB and AP-1
      activation in vivo and in vitro. Surfactant has limited effects on NF-kappaB and
      AP-1 activity.

PMID- 14653968
TI  - Extended abstracts of advance in lung inflammation and injury.

PMID- 14653967
TI  - Anti-inflammatory effect of methoxyphenamine compound in rat model of chronic
      obstructive pulmonary disease.
AB  - AIM: To evaluate the anti-inflammatory effect of methoxyphenamine compound (MC)
      on chronic obstructive pulmonary disease (COPD) in rats by measurement of
      proinflammatory cytokines, total and differential white cell counts (WCC) of
      bronchroalveolar lavage fluid (BALF). METHODS: Adult rat model of COPD (COPD
      group) was induced by intratracheal instillation of lipopolysaccharides and
      exposure to cigarette smoke. Treatment groups received different dosage of MC (3,
      9, and 27 mg daily, MC group) or prednisone (0.25 mg daily, P group)
      respectively. Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL
      1beta), interleukin-6 (IL-6), transforming growth factor beta (TGF-beta) of BALF
      were determined by ELISA. Total and differential WCC were performed after Giemsa
      staining. RESULTS: The levels of TNF-alpha, IL-1beta, IL-6, TGF-beta, total and
      differential WCC in BALF of MC groups were significantly decreased than that of
      COPD group (P<0.01), and there was no significant difference among MC groups.
      There was no significant decrease in the levels of TNF-alpha, IL-1beta and count
      of alveolar macrophages in P group compared to those of COPD group. More
      significant decrease in total WCC and neutrophils was found in P than in COPD
      group (P<0.01). CONCLUSION: MC has anti-inflammmatory effect in the rats with
      COPD.

PMID- 14653969
TI  - Family medicine: zebras among the horses.

PMID- 14653970
TI  - Glucosamine and chondroitin effective for knee osteoarthritis.

PMID- 14653971
TI  - Therapeutic knee taping decreases pain from knee osteoarthritis.

PMID- 14653972
TI  - Aspirin prevents preeclampsia and complications.

PMID- 14653973
TI  - Spinal manipulation effective for low back pain.

PMID- 14653974
TI  - What is the best method of diagnosing onychomycosis?

PMID- 14653975
TI  - Amoxicillin-clavulanate ineffective for suspected acute sinusitis.

PMID- 14653976
TI  - Discontinuing aspirin or warfarin optional before cataract surgery.

PMID- 14653977
TI  - Consider early cephalic version for breech presentation.

PMID- 14653978
TI  - Tubes for otitis media do not improve developmental outcomes.

PMID- 14653979
TI  - Patients with acute MI should be transferred for angioplasty.

PMID- 14653980
TI  - Irritable bowel syndrome: minimize testing, let symptoms guide treatment.

PMID- 14653981
TI  - Painful genital ulcers.

PMID- 14653982
TI  - Screening accuracy for late-life depression in primary care: a systematic review.
AB  - OBJECTIVE: To determine the accuracy of depression screening instruments for
      older adults in primary care. STUDY DESIGN: Systematic review. DATA SOURCES:
      MEDLINE, PsycINFO (search dates 1966 to January 2002), and the Cochrane database
      on depression, anxiety and neurosis. We also searched the second Guide to
      Clinical Preventive Services, the 1993 Agency for Health Care Policy and Research
      Clinical Practice Guideline on Depression, and recent systematic reviews. Hand
      checking of bibliographies and extensive peer review were also used to identify
      potential articles. OUTCOMES MEASURED: A predefined search strategy targeted only
      studies of adults aged 65 years or older in primary care or community settings,
      including long-term care. Articles were included in this review if they reported
      original data and tested depression screening instruments against a criterion
      standard, yielding sensitivity and specificity. RESULTS: Eighteen articles met
      criteria and are included in this review, representing 9 different screening
      instruments. The most commonly evaluated were the Geriatric Depression Scale (30-
      and 15-item versions), the Center for Epidemiologic Studies Depression Scale, and
      the SelfCARE(D). Differences in the performance of these 3 instruments were
      minimal; sensitivities ranged from 74% to 100% and specificities ranged from 53%
      to 98%. CONCLUSIONS: Accurate and feasible screening instruments are available
      for detecting late-life depression in primary care. More research is needed to
      determine the accuracy of depression screening instruments for demented
      individuals, and for those with subthreshold depressive disorders.

PMID- 14653983
TI  - Sexually transmitted disease: easier screening tests, single-dose therapies.

PMID- 14653984
TI  - Interpretation of confidence intervals.

PMID- 14653985
TI  - Clinical inquiries. What is the best way to manage benign paroxysmal positional
      vertigo?

PMID- 14653986
TI  - Clinical inquiries. Do statins cause myopathy?

PMID- 14653987
TI  - Clinical inquiries. What is the best hypnotic for use in the elderly?

PMID- 14653988
TI  - Clinical inquiries. Do systemic corticosteroids lessen symptoms in acute
      exacerbations of COPD?

PMID- 14653989
TI  - Clinical inquiries. Should we screen for ovarian cancer?

PMID- 14653990
TI  - Regulated mRNA stability of the Cdk inhibitor Rum1 links nutrient status to cell
      cycle progression.
AB  - BACKGROUND: The survival of a cell depends on continuous sensing of the
      nutritional environment and appropriate coordination of the cell cycle. The
      fission yeast Schizosaccharomyces pombe is an excellent model system in which to
      study these processes. In the presence of nutrients, fission yeast cells grow and
      divide, spending most of their time in G2; when nutrients are limiting, they are
      promoted into mitosis and arrest the cell cycle in G1. The molecular mechanisms
      underlying this response are currently unknown. RESULTS: Here, we show that
      expression of the fission yeast Cdk inhibitor Rum1, a key regulator of
      Cdc2/cyclin B in G1, is subject to regulated mRNA stability in response to
      nutrient deprivation. In complete minimal medium, rum1 mRNAs are very unstable.
      Following nitrogen starvation, rum1 mRNAs are rapidly stabilized, allowing the
      accumulation of Rum1 protein to delay the G1 phase of the subsequent cell cycle.
      Instability of rum1 mRNAs in complete minimal medium depends on the presence of
      AU-rich elements in the 3'UTR. We also show that lack of this mechanism has
      consequences in the mitotic cell cycle, in meiosis, and in the control of ploidy.
      CONCLUSION: We propose that mRNA stability is an important mechanism to fine tune
      the expression of the rum1 gene, in order to allow the production of appropriate
      levels of Rum1 protein in response to changes in the nutritional environment.

PMID- 14653991
TI  - Two putative acetyltransferases, san and deco, are required for establishing
      sister chromatid cohesion in Drosophila.
AB  - BACKGROUND: Sister chromatid cohesion is needed for proper alignment and
      segregation of chromosomes during cell division. Chromatids are linked by the
      multiprotein cohesin complex, which binds to DNA during G(1) and then establishes
      cohesion during S phase DNA replication. However, many aspects of the mechanisms
      that establish and maintain cohesion during mitosis remain unclear. RESULTS: We
      found that mutations in two evolutionarily conserved Drosophila genes, san
      (separation anxiety) and deco (Drosophila eco1), disrupt centromeric sister
      chromatid cohesion very early in division. This failure of sister chromatid
      cohesion does not require separase and is correlated with a failure of the
      cohesin component Scc1 to accumulate in centromeric regions. It thus appears that
      these mutations interfere with the establishment of centromeric sister chromatid
      cohesion. Secondary consequences of these mutations include activation of the
      spindle checkpoint, causing metaphase delay or arrest. Some cells eventually
      escape the block but incur many errors in anaphase chromosome segregation. Both
      san and deco are predicted to encode acetyltransferases, which transfer acetyl
      groups either to internal lysine residues or to the N terminus of other proteins.
      The San protein is itself acetylated, and it associates with the Nat1 and Ard1
      subunits of the NatA acetyltransferase. CONCLUSIONS: At least two diverse
      acetyltransferases play vital roles in regulating sister chromatid cohesion
      during Drosophila mitosis.

PMID- 14653993
TI  - Mental representation of number in different numerical forms.
AB  - How are numerical operations implemented within the human brain? It has been
      suggested that there are at least three different codes for representing number:
      a verbal code that is used to manipulate number words and perform mental
      numerical operations (e.g., multiplication), a visual code that is used to decode
      frequently used visual number forms (e.g., Arabic digits), and an abstract analog
      code that may be used to represent numerical quantities. Furthermore, each of
      these codes is associated with a different neural substrate. We extend these
      studies using dense-sensor event-related EEG recording techniques to investigate
      the temporal pattern of notation-specific effects observed in a parity judgement
      (odd versus even) task in which single numbers were presented in one of four
      different numerical notations. Contrasts between different notations demonstrated
      clear modulations in the visual evoked potentials (VEP) recorded. We observed
      increased amplitudes for the P1 and N1 components of the VEP that were specific
      to Arabic numerals and to dot configurations but differed for random and
      recognizable (die-face) dot configurations. These results demonstrate clear,
      notation-specific differences in the time course of numerical information
      processing and provide electrophysiological support for the triple-code model of
      numerical representation.

PMID- 14653992
TI  - PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) regulates cell growth and
      proliferation via the downstream targets ribosomal S6 kinase 1 (S6K1) and
      eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). We have
      identified phosphatidic acid (PA) as a mediator of mitogenic activation of mTOR
      signaling. In this study, we set out to test the hypotheses that phospholipase D
      1 (PLD1) is an upstream regulator of mTOR and that the previously reported S6K1
      activation by Cdc42 is mediated by PLD1. RESULTS: Overexpression of wild-type
      PLD1 increased S6K1 activity in serum-stimulated cells, whereas a catalytically
      inactive PLD1 exerted a dominant-negative effect on S6K1. More importantly,
      eliminating endogenous PLD1 by RNAi led to drastic inhibition of serum-stimulated
      S6K1 activation and 4E-BP1 hyperphosphorylation in both HEK293 and COS-7 cells.
      Knockdown of PLD1 also resulted in reduced cell size, suggesting a critical role
      for PLD1 in cell growth control. Using a rapamycin-resistant S6K1 mutant, Cdc42's
      action was demonstrated to be through the mTOR pathway. When Cdc42 was mutated in
      a region specifically required for PLD1 activation, its ability to activate S6K1
      in the presence of serum was hindered. However, when exogenous PA was used as a
      stimulus, the PLD1-inactive Cdc42 mutant behaved similarly to the wild-type
      protein. CONCLUSIONS: Our observations reveal the involvement of PLD1 in mTOR
      signaling and cell size control, and provide a molecular mechanism for Cdc42
      activation of S6K1. A new cascade is proposed to connect mitogenic signals to
      mTOR through Cdc42, PLD1, and PA.

PMID- 14653994
TI  - Light regulates the cell cycle in zebrafish.
AB  - The timing of cell proliferation is a key factor contributing to the regulation
      of normal growth. Daily rhythms of cell cycle progression have been documented in
      a wide range of organisms. However, little is known about how environmental,
      humoral, and cell-autonomous factors contribute to these rhythms. Here, we
      demonstrate that light plays a key role in cell cycle regulation in the
      zebrafish. Exposure of larvae to light-dark (LD) cycles causes a range of
      different cell types to enter S phase predominantly at the end of the day. When
      larvae are raised in constant darkness (DD), a low level of arrhythmic S phase is
      observed. In addition, light-entrained cell cycle rhythms persist for several
      days after transfer to DD, both observations pointing to the involvement of the
      circadian clock. We show that the number of LD cycles experienced is essential
      for establishing this rhythm during larval development. Furthermore, we reveal
      that the same phenomenon exists in a zebrafish cell line. This represents the
      first example of a vertebrate cell culture system where circadian rhythms of the
      cell cycle are observed. Thus, we implicate the cell-autonomous circadian clock
      in the regulation of the vertebrate cell cycle by light.

PMID- 14653995
TI  - Identification of a subunit of a novel Kleisin-beta/SMC complex as a potential
      substrate of protein phosphatase 2A.
AB  - Protein phosphatase 2A (PP2A) holoenzymes consist of a catalytic C subunit, a
      scaffolding A subunit, and one of several regulatory B subunits that recruit the
      AC dimer to substrates. PP2A is required for chromosome segregation, but PP2A's
      substrates in this process remain unknown. To identify PP2A substrates, we
      carried out a two-hybrid screen with the regulatory B/PR55 subunit. We isolated a
      human homolog of C. elegans HCP6, a protein distantly related to the condensin
      subunit hCAP-D2, and we named this homolog hHCP-6. Both C. elegans HCP-6 and
      condensin are required for chromosome organization and segregation. HCP-6 binding
      partners are unknown, whereas condensin is composed of the structural maintenance
      of chromosomes proteins SMC2 and SMC4 and of three non-SMC subunits. Here we show
      that hHCP-6 becomes phosphorylated during mitosis and that its dephosphorylation
      by PP2A in vitro depends on B/PR55, suggesting that hHCP-6 is a B/PR55-specific
      substrate of PP2A. Unlike condensin, hHCP-6 is localized in the nucleus in
      interphase, but similar to condensin, hHCP-6 associates with chromosomes during
      mitosis. hHCP-6 is part of a complex that contains SMC2, SMC4, kleisin-beta, and
      the previously uncharacterized HEAT repeat protein FLJ20311. hHCP-6 is therefore
      part of a condensin-related complex that associates with chromosomes in mitosis
      and may be regulated by PP2A.

PMID- 14653996
TI  - Regulation of stem cell maintenance and transit amplifying cell proliferation by
      tgf-beta signaling in Drosophila spermatogenesis.
AB  - The continuous and steady supply of transient cell types such as skin, blood and
      gut depends crucially on the controlled proliferation of stem cells and their
      transit amplifying progeny. Although it is thought that signaling to and from
      support cells might play a key role in these processes, few signals that might
      mediate this interaction have been identified. During spermatogenesis in
      Drosophila, the asymmetric division of each germ line stem cell results in its
      self-renewal and the production of a committed progenitor that undergoes four
      mitotic divisions before differentiating while remaining in intimate contact with
      somatic support cells [1]. Previous data have suggested that TGF-beta signaling
      pathway components punt and schnurri are required in the somatic support cells to
      restrict germ cell proliferation. Here, by contrast, we show that the maintenance
      and proliferation of germ line stem cells and their progeny depends upon their
      ability to transduce the activity of a somatically expressed TGF-beta ligand, the
      BMP5/8 ortholog Glass Bottom Boat. We further demonstrate that TGF-beta signaling
      represses the expression of the Bam protein, which is both necessary and
      sufficient for germ cell differentiation, thereby maintaining germ line stem
      cells and spermatogonia in their proliferative state.

PMID- 14653997
TI  - Ubiquitin-mediated proteasome activity is required for agonist-induced
      endocytosis of GluRs.
AB  - Recent studies documenting a role for local protein synthesis in synaptic
      plasticity have lead to interest in the opposing process, protein degradation, as
      a potential regulator of synaptic function. The ubiquitin-conjugation system
      identifies, modifies, and delivers proteins to the proteasome for degradation. We
      found that both the proteasome and ubiquitin are present in the soma and
      dendrites of hippocampal neurons. As the trafficking of glutamate receptors
      (GluRs) is thought to underlie some forms of synaptic plasticity, we examined
      whether blocking proteasome activity affects the agonist-induced internalization
      of GluRs in cultured hippocampal neurons. Treatment with the glutamate agonist
      AMPA induced a robust internalization of GluRs. In contrast, brief pretreatment
      with proteasome inhibitors completely prevented the internalization of GluRs. To
      distinguish between a role for the proteasome and a possible diminution of the
      free ubiquitin pool, we expressed a chain elongation defective ubiquitin mutant
      (UbK48R), which causes premature termination of polyubiquitin chains but,
      importantly, can serve as a substrate for mono-ubiquitin-dependent processes.
      Expression of K48R in neurons severely diminished AMPA-induced internalization
      establishing a role for the proteasome. These data demonstrate the acute (e.g.,
      minutes) regulation of synaptic function by the ubiquitin-proteasome pathway in
      mammalian neurons.

PMID- 14653998
TI  - Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3
      regulates cell polarity in mammalian epithelia.
AB  - The mammalian homologs of the C. elegans partitioning-defective (Par) proteins
      have been demonstrated to be necessary for establishment of cell polarity. In
      mammalian epithelia, the Par3/Par6/aPKC polarity complex is localized to the
      tight junction and regulates its formation and positioning with respect to
      basolateral and apical membrane domains. Here we demonstrate a previously
      undescribed phosphorylation-dependent interaction between a mammalian homolog of
      the C. elegans polarity protein Par5, 14-3-3, and the tight junction-associated
      protein Par3. We identify phosphorylated serine 144 as a site of 14-3-3 binding.
      Expression of a Par3 mutant that contains serine 144 mutated to alanine (S144A)
      results in defects in epithelial cell polarity. In addition, overexpression of 14
      3-3zeta results in a severe disruption of polarity, whereas overexpression of a
      14-3-3 mutant that is defective in binding to phosphoproteins has no effect on
      cell polarity. Together, these data suggest a novel, phosphorylation-dependent
      mechanism that regulates the function of the Par3/Par6/aPKC polarity complex
      through 14-3-3 binding.

PMID- 14653999
TI  - The F box protein AFR is a positive regulator of phytochrome A-mediated light
      signaling.
AB  - Light is an important environmental cue to plants, and much of their physiology
      is influenced by light. The light signals that drive these responses are
      perceived by photoreceptors including the red/far-red responsive phytochromes
      (phyA-E). In addition to direct effects, light also exerts its influence by
      modifying the rhythms generated by the circadian clock. In Arabidopsis thaliana,
      the molecular makeup of the interface between the central clock and its
      input/output pathways is not fully defined, but a major point of control is
      likely to be protein turnover mediated by the ubiquitin/26S proteasome system. To
      identify additional constituents of this interface, stable double-stranded RNA
      interference (RNAi) was used to reduce mRNA levels of rhythmically expressed
      candidate genes encoding putative components of E3 ubiquitin ligases (i.e., F box
      and RING finger proteins), followed by screening of the transgenic plants for
      circadian and light signaling defects. RNAi lines with diminished expression of
      the novel gene ATTENUATED FAR-RED RESPONSE (AFR) display phenotypes consistent
      with impaired phyA-mediated light signaling. Furthermore, AFR is a true SCF E3
      ubiquitin ligase component. SCF(AFR) is expected to mediate the turnover of a
      repressor of phyA signaling, possibly to prepare the plant to receive light
      signals at dawn.

PMID- 14654000
TI  - A serpin regulates dorsal-ventral axis formation in the Drosophila embryo.
AB  - Extracellular serine protease cascades have evolved in vertebrates and
      invertebrates to mediate rapid, local reactions to physiological or pathological
      cues. The serine protease cascade that triggers the Toll signaling pathway in
      Drosophila embryogenesis shares several organizational characteristics with those
      involved in mammalian complement and blood clotting. One of the hallmarks of such
      cascades is their regulation by serine protease inhibitors (serpins). Serpins act
      as suicide substrates and are cleaved by their target protease, forming an
      essentially irreversible 1:1 complex. The biological importance of serpins is
      highlighted by serpin dysfunction diseases, such as thrombosis caused by a
      deficiency in antithrombin. Here, we describe how a serpin controls the serine
      protease cascade, leading to Toll pathway activation. Female flies deficient in
      Serpin-27A produce embryos that lack dorsal-ventral polarity and show uniform
      high levels of Toll signaling. Since this serpin has been recently shown to
      restrain an immune reaction in the blood of Drosophila, it demonstrates that
      proteolysis can be regulated by the same serpin in different biological contexts.

PMID- 14654001
TI  - Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2
      to kinetochores.
AB  - Members of the Ndc80/Nuf2 complex have been shown in several systems to be
      important in formation of stable kinetochore-microtubule attachments and
      chromosome alignment in mitosis. In HeLa cells, we have shown that depletion of
      Nuf2 by RNA interference (RNAi) results in a strong prometaphase block with an
      active spindle checkpoint, which correlates with low but detectable Mad2 at
      kinetochores that have no or few stable kinetochore microtubules. Another RNAi
      study in HeLa cells reported that Hec1 (the human Ndc80 homolog) is required for
      Mad1 and Mad2 binding to kinetochores and that kinetochore bound Mad2 does not
      play a role in generating and maintaining the spindle assembly checkpoint. Here,
      we show that depletion of either Nuf2 or Hec1 by RNAi in HeLa cells results in
      reduction of both proteins at kinetochores and in the cytoplasm. Mad1 and Mad2
      concentrate at kinetochores in late prophase/early prometaphase but become
      depleted by 5-fold or more over the course of the prometaphase block, which is
      Mad2 dependent. The reduction of Mad1 and Mad2 is reversible upon spindle
      depolymerization. Our observations support a model in which Nuf2 and Hec1
      function to prevent microtubule-dependent stripping of Mad1 and Mad2 from
      kinetochores that have not yet formed stable kinetochore-microtubule attachments.

PMID- 14654002
TI  - Stella is a maternal effect gene required for normal early development in mice.
AB  - stella is a novel gene specifically expressed in primordial germ cells, oocytes,
      preimplantation embryos, and pluripotent cells. It encodes a protein with a SAP
      like domain and a splicing factor motif-like structure, suggesting possible roles
      in chromosomal organization or RNA processing. Here, we have investigated the
      effects of a targeted mutation of stella in mice. We show that while matings
      between heterozygous animals resulted in the birth of apparently normal stella
      null offspring, stella-deficient females displayed severely reduced fertility due
      to a lack of maternally inherited Stella-protein in their oocytes. Indeed, we
      demonstrate that embryos without Stella are compromised in preimplantation
      development and rarely reach the blastocyst stage. stella is thus one of few
      known mammalian maternal effect genes, as the phenotypic effect on embryonic
      development is mainly a consequence of the maternal stella mutant genotype.
      Furthermore, we show that STELLA that is expressed in human oocytes is also
      expressed in human pluripotent cells and in germ cell tumors. Interestingly,
      human chromosome 12p, which harbours STELLA, is consistently overrepresented in
      these tumors. These findings suggest a similar role for STELLA during early human
      development as in mice and a potential involvement in germ cell tumors.

PMID- 14654003
TI  - Positive selection on a human-specific transcription factor binding site
      regulating IL4 expression.
AB  - A single nucleotide polymorphism in the promoter of the multifunctional cytokine
      Interleukin 4 (IL4) affects the binding of NFAT, a key transcriptional activator
      of IL4 in T cells. This regulatory polymorphism influences the balance of
      cytokine signaling in the immune system, with important consequences-positive and
      negative-for human health. We determined that the NFAT binding site is unique to
      humans; it arose by point mutation along the lineage separating humans from other
      great apes. We show that its frequency distribution among human subpopulations
      has been shaped by the balance of selective forces on IL4's diverse roles. New
      statistical approaches, based on parametric and nonparametric comparisons to
      neutral variants typed in the same individuals, indicate that differentiation
      among subpopulations at the IL4 promoter polymorphism is too great to be
      attributed to neutral drift. The allele frequencies of this binding site
      represent local adaptation to diverse pathogenic challenges; disease states
      associated with the common derived allele are side-effects of positive selection
      on other IL4 functions.

PMID- 14654005
TI  - Researchers protest at GM crop debate.

PMID- 14654006
TI  - Raising profile.( Colin Blakemore, the new chief executive of the Medical
      Research Council interviewed by Nigel Williams).

PMID- 14654007
TI  - Q & A.

PMID- 14654008
TI  - Bubble speak.

PMID- 14654009
TI  - Honeybee navigation.

PMID- 14654010
TI  - Heterochromatin: silence is golden.

PMID- 14654011
TI  - A novel interaction motif, SARAH, connects three classes of tumor suppressor.

PMID- 14654012
TI  - Population genomics: finding the variants of mass disruption.

PMID- 14654013
TI  - Eukaryotic chaperonins: lubricating the folding of WD-repeat proteins.

PMID- 14654014
TI  - Visual cortex: seeing motion.

PMID- 14654015
TI  - Tubulogenesis: a role for the apical extracellular matrix?

PMID- 14654017
TI  - Transcription elongation: TLKing to chromatin?

PMID- 14654019
TI  - NMDA receptors: neural map designers and refiners?

PMID- 14654018
TI  - Organelle transport: a park-and-ride system for melanosomes.

PMID- 14654020
TI  - Plant signalling: calcium first and second.

PMID- 14654016
TI  - Phosphorylation: polo kinase joins an elite club.

PMID- 14654021
TI  - microRNAs: runts of the genome assert themselves.

PMID- 14654022
TI  - Radiofrequency ablation of renal cell carcinoma.
AB  - Small renal cell carcinomas of less than 4 cm diameter have been detected
      increasingly in asymptomatic patients because of the widespread use of cross
      sectional imaging. Radical or partial nephrectomy is generally considered the
      reference for the treatment of a solitary renal cell carcinoma. However, for
      those patients who are not candidates for surgery, minimally invasive procedures
      may be desirable. Although percutaneous radiofrequency ablation for the treatment
      of renal cell carcinoma is a recent innovation, the results of preliminary
      clinical series and animal studies are encouraging, and show it to be technically
      feasible with minimal morbidity. In this article, we review the technique,
      indications, imaging findings, as well as the results of clinical and animal
      studies of radiofrequency ablation for the treatment of renal cell carcinoma.

PMID- 14654023
TI  - Imaging of sacral fractures.
AB  - The article discusses traumatic, insufficiency and pathological sacral fractures.
      Special attention is paid to the biomechanics and subsequent classification of
      traumatic sacral fractures.

PMID- 14654024
TI  - Differential diagnosis of intracranial lesions with high signal on T1 or low
      signal on T2-weighted MRI.
AB  - Magnetic resonance imaging (MRI) is the preferred technique for examining
      intracranial pathology in the non-acute setting in most cases. The aim of this
      review is to demonstrate the imaging appearances on unenhanced spin-echo MRI of
      lesions that show characteristic, unusual signal changes, which occur due to the
      presence of fat, cholesterol, paramagnetic substances, rapidly flowing fluids,
      air, cortical bone or calcification. The nature of the MRI signal, together with
      the anatomical location of the lesion should allow the provision of a narrow
      differential diagnosis, before the use of intravenous contrast medium or
      additional imaging sequences.

PMID- 14654025
TI  - Mesenchymal tumours of the thorax: CT findings and pathological features.
AB  - Mesenchymal tumours of the thorax are uncommon and may originate from the muscle,
      bone, cartilage, vessel, nerves, fat and fibrous tissue. These tumours occur at
      different sites including the lung, pleura, mediastinum or chest wall.
      Mesenchymal tumours tend to show protean and non-specific imaging
      characteristics. However, in some instances, the imaging characteristics of the
      tumour may allow a specific diagnosis to be made, such as with lipoid or vascular
      tumours.

PMID- 14654027
TI  - Observer variation in the detection of colorectal neoplasia on double-contrast
      barium enema: implications for colorectal cancer screening and training.
AB  - AIM: To assess inter-observer error for the diagnosis of neoplasia on double
      contrast barium enema (DCBE) in the light of claims that no additional
      interpretative training would be needed for implementation in a national
      screening programme. MATERIALS AND METHODS: 10 experts, 10 consultants, and 10
      experienced trainees each reported 20 DCBE studies, of which two showed cancer,
      three showed large polyps, four showed small polyps, and 12 were normal. Inter
      observer variation was compared using odds ratios with the trainee group as
      reference (baseline group). RESULTS: Experts were significantly more likely to
      correctly identify neoplasia on DCBE than trainees. The odds of a correct
      diagnosis for experts were 2.79 (95% CI 2.04, 3.81) for cancer, 2.36 (1.88, 2.97)
      for large polyps, and 3.50 (1.98, 6.18) for small polyps. While consultants were
      more likely to correctly diagnose a large polyp than trainees, 1.45 (1.15, 1.84),
      there was no significant difference between these two groups for the correct
      diagnosis of either cancer, 1.24 (0.52, 2.96), or small polyps, 1.26 (0.83,
      1.90). A cancer was missed by 6 (60%) experts, 9 (90%) consultants, and 8 (80%)
      trainees. Large polyps were missed by 4 (40%) experts, 5 (50%) consultants, and 6
      (60%) trainees. There was no significant difference between any group when false
      positive diagnoses were considered. CONCLUSIONS: There is considerable inter
      observer perceptive error for the diagnosis of neoplasia on DCBE. Experts
      performed significantly better than other observers but the overall standard of
      performance was poor, even amongst experts.

PMID- 14654028
TI  - Optimization of scanning parameters for multi-slice CT colonography: experiments
      with synthetic and animal phantoms.
AB  - AIM: To determine the optimal collimation, pitch, tube current and reconstruction
      interval for multi-slice computed tomography (CT) colonography with regard to
      attaining satisfactory image quality while minimizing patient radiation dose.
      MATERIALS AND METHODS: Multi-slice CT was performed on plastic, excised pig colon
      and whole pig phantoms to determine optimal settings. Performance was judged by
      detection of simulated polyps and statistical measures of the image parameters.
      Fat and muscle conspicuity was measured from images of dual tube-current
      prone/supine patient data to derive a measure of tube current effects on tissue
      contrast. RESULTS: A collimation of 4 x 2.5 mm was sufficient for detection of
      polyps 4 mm and larger, provided that a reconstruction interval of 1.25 mm was
      used. A pitch of 1.5 allowed faster scanning and reduced radiation dose without
      resulting in a loss of important information, i.e. detection of small polyps,
      when compared with a pitch of 0.75. Tube current and proportional radiation dose
      could be lowered substantially without deleterious effects on the detection of
      the air-mucosal interface, however, increased image noise substantially reduced
      conspicuity of different tissues. CONCLUSION: An optimal image acquisition set-up
      of 4 x 2.5 mm collimation, reconstruction interval of 1.25 mm, pitch of 1.5 and
      dual prone/supine scan of 40/100 mA tube current is proposed for our institution
      for scanning symptomatic patients. Indications are that where CT colonography is
      used for colonic polyp screening in non-symptomatic patients, a 40 mA tube
      current could prove satisfactory for both scans.

PMID- 14654029
TI  - Antenatal hydronephrosis: negative predictive value of normal postnatal
      ultrasound--a 5-year study.
AB  - AIM: To determine whether normal postnatal ultrasound, as part of a strict
      screening protocol for the detection and follow-up of antenatal hydronephrosis,
      effectively excludes the majority of babies with congenital urinary tract
      abnormalities that would otherwise present with a urinary tract infection.
      MATERIALS AND METHODS: We retrospectively reviewed all babies who had postnatal
      follow-up of antenatally detected hydronephrosis over a 5-year period at our
      institution, a district general Trust with a specialist paediatric unit. We then
      studied all babies presenting with urinary tract infection before their first
      birthday to our institution over the same period. By cross-referencing these two
      study groups we were able to determine which babies developed a urinary tract
      infection having been previously discharged after normal postnatal ultrasound.
      RESULTS: Four hundred and twenty-five babies had postnatal follow-up of antenatal
      hydronephrosis. Of these, 284 were investigated with ultrasound alone. In the
      same 5-year period, 230 babies presented with urinary tract infection before
      their first birthday. Only three of these babies had been previously discharged
      after normal postnatal ultrasound. The negative predictive value of a normal
      postnatal ultrasound was therefore 98.9% (281/284) for babies who subsequently
      presented with a urinary tract infection before their first birthday. CONCLUSION:
      Careful antenatal and postnatal ultrasound with strict protocols is effective in
      detecting congenital renal tract abnormalities. Infants discharged after normal
      postnatal ultrasound are highly unlikely to still have an undetected urinary
      tract abnormality. We suggest that all babies with antenatal hydronephrosis are
      started on prophylactic antibiotics at birth, pending further investigation. All
      babies without features of severe obstruction antenatally should have their
      postnatal ultrasound delayed for a month. We recommend selective use of
      micturating cystourethrogram (MCUG), and delaying this investigation until the
      baby is 3 to 4 months old to allow for spontaneous resolution of vesicoureteric
      reflux. We do not believe that all babies with antenatal hydronephrosis require
      MCUG, providing a clear protocol is followed.

PMID- 14654030
TI  - The effect of reporting speed on plain film reporting errors.
AB  - AIM: To determine whether reporting plain films at faster rates lead to a
      deterioration in accuracy. METHODS: Fourteen consultant radiologists were asked
      to report a total of 90 radiographs in three sets of 30. They reported the first
      set at the rate they would report normally and the subsequent two sets in two
      thirds and one half of the original time. The 90 radiographs were the same for
      each radiologist, however, the order was randomly generated for each. RESULTS:
      There was no significant difference in overall accuracy for each of the three
      film sets (p=0.74). Additionally no significant difference in the total number of
      false-negatives for each film set was detected (p=0.14). However, there was a
      significant decrease in the number of false-positive reports when the
      radiologists were asked to report at higher speeds (p=0.003). CONCLUSIONS: When
      reporting accident and emergency radiographs increasing reporting speed has no
      overall effect upon accuracy, however, it does lead to less false-positive
      reports.

PMID- 14654031
TI  - Magnetic resonance imaging of the cervical spine: frequency of degenerative
      changes in the intervertebral disc with relation to age.
AB  - AIM: To ascertain the level at which intervertebral disc degeneration of the
      cervical spine most commonly occurs in each decade from 20-79 years. MATERIALS
      AND METHODS: Using computer analysis, we retrospectively assessed the mean signal
      intensity from each cervical disc from T2-weighted spin-echo images in 60
      symptomatic patients (10 per decade from the third to eighth inclusive). RESULTS:
      Age, disc level and interaction between age and level were highly significant
      predictors for the magnetic resonance imaging (MRI) mean signal intensity from
      intervertebral discs (p<0.0001 for all three terms). The MRI signals were
      generally lower as age increased and also for the higher discs (C2-C3, etc).
      CONCLUSION: In our study we have shown that in younger patients the higher discs
      are more frequently affected by degeneration than the lower ones. As age
      increases, the process of degeneration becomes more generalized with less
      variability between discs.

PMID- 14654032
TI  - A comparative roentgenographic analysis of the lumbar spine in male army recruits
      with and without lower back pain.
AB  - AIM: To determine whether there is an association between lumbar spine
      radiographic findings and reported current and/or past lower back pain (LBP).
      MATERIALS AND METHODS: Four hundred and sixty-four age-matched (mean age 18
      years+/-2 months) consecutive male army recruits were examined. Half of them had
      a history of episodes of LBP. An orthopaedic evaluation (including radiographs of
      the lumbar spine) is part of the routine medical examination for all military
      recruits. Two senior orthopaedic surgeons and one radiologist who performed the
      morphological measurements assessed the radiographs. RESULTS: We found an
      increased frequency of right-sided scoliosis, lumbar lordosis, sacral
      lumbarization, wedge vertebra, bilateral spondylolysis of L5 and/or a sagittal
      diameter of less than 12 mm among the recruits with LBP. No such association was
      found with spina bifida, left-sided scoliosis, hemi-lumbarization, sacralization
      and hemi-sacralization, Schmorl's nodules or mild degenerative changes.
      CONCLUSION: Given that radiographic screening shows that LBP is more common in
      those with spinal deformity it may be a reasonable means of predicting which
      individuals are more likely to develop LBP.

PMID- 14654033
TI  - Acute ureterolithiasis: incidence of secondary signs on unenhanced helical CT and
      influence on patient management.
AB  - AIM: The purpose of this study was to determine the incidence of secondary signs
      associated with ureteral stones on unenhanced helical computed tomography (CT) of
      patients with acute renal colic, and to correlate these with patient management
      and outcome. MATERIALS AND METHODS: One hundred and ten patients with
      ureterolithiasis were evaluated prospectively for the secondary signs of
      obstruction on unenhanced helical CT. Our attention was focused primarily on the
      presence or absence of seven secondary signs on unenhanced helical CT, including
      hydronephrosis, unilateral renal enlargement, perinephric oedema, unilateral
      absence of the white pyramid, hydroureter, periureteral oedema and lateroconal
      fascial thickening. RESULTS: Of the 110 patients, 91 (82.7%) had hydroureter, 88
      (80%) had hydronephrosis, 65 (59%) had periureteric oedema and 63 (57.2%) had
      unilateral renal enlargement. Ninety stones passed spontaneously and 21 required
      intervention. CONCLUSION: Secondary signs of urinary tract obstruction are useful
      and supportive findings in interpretation of the CT examination. In our
      experience, the most reliable signs indicating ureteral obstruction are
      hydroureter, hydronephrosis, periureteral oedema and unilateral renal
      enlargement, respectively. In addition, stones larger than 6 mm, located within
      the proximal two thirds of the ureter, and seen associated with five or more the
      secondary signs of obstruction, are more likely to require endoscopic removal
      and/or lithotripsy.

PMID- 14654034
TI  - Peliosis hepatis: central "fast surge" ultrasound enhancement and multislice CT
      appearances.

PMID- 14654035
TI  - Category specificity in normal episodic learning: applications to object
      recognition and category-specific agnosia.
AB  - Studies of patients with category-specific agnosia (CSA) have given rise to
      multiple theories of object recognition, most of which assume the existence of a
      stable, abstract semantic memory system. We applied an episodic view of memory to
      questions raised by CSA in a series of studies examining normal observers' recall
      of newly learned attributes of familiar objects. Subjects first learned to
      associate arbitrarily assigned colors or textures to objects in a training phase,
      and then attempted to report the newly learned attribute of each object in a
      recall task. Our subjects' pattern of recall errors was similar both
      quantitatively and qualitatively to the identification deficits among patients
      with CSA for biological objects. Furthermore, errors tended to reflect
      conceptually and structurally based confusions. We suggest that object
      identification involves recruitment and integration of information across
      distributed episodic memories and that this process is susceptible to
      interference from objects that are structurally similar and conceptually related.

PMID- 14654036
TI  - Out of one's mind: a study of involuntary semantic memories.
AB  - The study of memories that pop into one's mind without any conscious attempt to
      retrieve them began only recently. While there are some studies on involuntary
      autobiographical memories (e.g., ) research on involuntary semantic memories or
      mind-popping is virtually non-existent. The latter is defined as an involuntary
      conscious occurrence of brief items of one's network of semantic knowledge. The
      recall of these items (e.g., a word, a name, a tune) is not accompanied by
      additional contextual information and/or involvement of self-a standard feature
      of involuntary autobiographical memories. The paper reports several diary and
      questionnaire studies which looked into the nature and frequency of occurrence of
      these memories. The data show that people do experience involuntary semantic
      memories which tend to occur without any apparent cues while being engaged in
      relatively automatic activities. Possible mechanisms of involuntary semantic
      memories are discussed (e.g., very long-term priming), and the results of the
      study provide information on the possible duration of the priming effects in
      everyday life. Related theoretical and methodological issues and future avenues
      of research in this neglected area are outlined.

PMID- 14654037
TI  - Evidence against a central bottleneck during the attentional blink: multiple
      channels for configural and featural processing.
AB  - When a visual target is identified, there is a period of several hundred
      milliseconds when the processing of subsequent targets is impaired, a phenomenon
      labeled the attentional blink (AB). The emerging consensus is that the
      identification of a visual target temporarily occupies a limited attentional
      resource that is essential for all visual perception. The present results
      challenge this view. With the same digit discrimination task that impaired
      subsequent letter discrimination for several hundred milliseconds, we found no
      disruption of subsequent face discrimination. These results suggest that all
      stimuli do not compete for access to a single resource for visual perception. We
      propose a multi-channel account of interference in the AB paradigm.

PMID- 14654038
TI  - Applications of affinity chromatography in proteomics.
AB  - Affinity chromatography is a powerful protein separation method that is based on
      the specific interaction between immobilized ligands and target proteins.
      Peptides can also be separated effectively by affinity chromatography through the
      use of peptide-specific ligands. Both two-dimensional electrophoresis (2-DE)- and
      non-2-DE-based proteomic approaches benefit from the application of affinity
      chromatography. Before protein separation by 2-DE, affinity separation is used
      primarily for preconcentration and pretreatment of samples. Those applications
      entail the removal of one protein or a class of proteins that might interfere
      with 2-DE resolution, the concentration of low-abundance proteins to enable them
      to be visualized in the gel, and the classification of total protein into two or
      more groups for further separation by gel electrophoresis. Non-2-DE-based
      approaches have extensively employed affinity chromatography to reduce the
      complexity of protein and peptide mixtures. Prior to mass spectrometry (MS),
      preconcentration and capture of specific proteins or peptides to enhance
      sensitivity can be accomplished by using affinity adsorption. Affinity
      purification of protein complexes followed by identification of proteins by MS
      serves as a powerful tool for generating a map of protein-protein interactions
      and cellular locations of complexes. Affinity chromatography of peptide mixtures,
      coupled with mass spectrometry, provides a tool for the study of protein
      posttranslational modification (PTM) sites and quantitative proteomics.
      Quantitation of proteomes is possible via the use of isotope-coded affinity tags
      and isolation of proteolytic peptides by affinity chromatography. An emerging
      area of proteomics technology development is miniaturization. Affinity
      chromatography is becoming more widely used for exploring PTM and protein-protein
      interactions, especially with a view toward developing new general tag systems
      and strategies of chemical derivatization on peptides for affinity selection.
      More applications of affinity-based purification can be expected, including
      increasing the resolution in 2-DE, improving the sensitivity of MS
      quantification, and incorporating purification as part of multidimensional liquid
      chromatography experiments.

PMID- 14654039
TI  - Development and validation of a method to determine the unbound paclitaxel
      fraction in human plasma.
AB  - Paclitaxel is pharmaceutically formulated in a mixture of Cremophor EL and
      ethanol (1:1, v/v). The unbound fraction of the anticancer drug paclitaxel in
      plasma is dependent on both plasma protein binding and entrapment in Cremophor EL
      micelles. We have developed a simple and reproducible method for the
      quantification of the unbound paclitaxel fraction in human plasma. Human plasma
      was spiked with [3H]paclitaxel and [14C]glucose (unbound reference) and incubated
      at 37 degrees C for 30 min. Plasma ultrafiltrate was prepared by a micropartition
      system (MPS-1) and collected in a sample cup containing 100 microl of plasma to
      prevent the loss of paclitaxel due to adsorption. The radionuclides were
      separated after combustion of the biological samples using a sample oxidizer and
      the radioactivity was determined by liquid scintillation counting. The unbound
      fraction of paclitaxel was calculated by dividing the ratios of 3H and 14C in
      plasma ultrafiltrate and in plasma. The method was thoroughly validated using
      human plasma spiked with pharmacologically relevant concentrations of paclitaxel
      (10-1000 ng/ml) and Cremophor EL (0.25-2.0%). The method was precise, with a
      within-day precision ranging from 3.9 to 11.0% and a between-day precision
      ranging from 5.8 to 13.1%. In patient plasma with low serum albumin values
      containing 1% of Cremophor EL, the unbound fraction appeared to be significantly
      higher than that in plasma with normal albumin values. The determination of the
      unbound fraction of paclitaxel proved to be stable during a 10-week storage at 
      20 degrees C. Furthermore, the assay was applicable in patient samples. This
      assay can be used to determine the unbound fraction of paclitaxel in plasma.
      Moreover, its design should allow the determination of the unbound concentrations
      of other hydrophobic drugs.

PMID- 14654040
TI  - Validation of fluorescence-labeled artificial nonhuman sequences for single
      strand conformation polymorphism mutation detection in familial
      hypercholesterolemia.
AB  - We developed a two-in-one, polymerase chain reaction (PCR)-based method with a
      specific amplification step and a universal amplification step in one tube to
      screen for the presence of DNA variations. The method relies on fluorescence
      labeled artificial nonhuman sequences for mutation detection. To document
      utility, we applied this method as a high-throughput capillary single-strand
      conformation polymorphism screening system to identify 30 mutations in the low
      density lipoprotein receptor gene. The sensitivity of mutant allele detection
      compared to wild-type allele detection was 93%. We conclude that the "two-in-one
      PCR" is sensitive, simple, and cost effective.

PMID- 14654041
TI  - Pyrophosphorolysis by Type II DNA polymerases: implications for
      pyrophosphorolysis-activated polymerization.
AB  - We find that Type II DNA polymerases can catalyze pyrophosphorolysis, the reverse
      reaction of DNA polymerization. This property is applied utilizing
      pyrophosphorolysis-activated polymerization (PAP), a method of nucleic acid
      amplification using serial coupling of pyrophosphorolysis and polymerization. PAP
      can be used for ultrarare allele detection (detection of minimal residual disease
      and cancer risk assessment through measurement of mutation load) and for
      microarray-based scanning for unknown mutations. Herein, we show that Type II DNA
      polymerases efficiently catalyze template-dependent pyrophosphorolysis to
      activate oligonucleotides blocked at their 3' termini with acyclonucleotides in
      which a 2-hydroxyethoxymethyl group substitutes for the 2'-deoxyribofuranosyl
      sugar. Type II archeon DNA polymerases Vent (exo-) and Pfu (exo-) can be utilized
      for PAP or a bidirectional form of PAP with acyclonucleotide-blocked
      oligonucleotides, but not with dideoxynucleotide-blocked oligonucleotides. In
      contrast, a Type I DNA polymerase, TaqFS, can utilize either acyclonucleotide
      blocked or dideoxynucleotide-blocked oligonucleotides. These findings expand the
      potential of nascent PAP technology.

PMID- 14654042
TI  - Determination of amino acids in cell culture and fermentation broth media using
      anion-exchange chromatography with integrated pulsed amperometric detection.
AB  - Cell culture and fermentation broth media are used in the manufacture of
      biotherapeutics and many other biological materials. Characterizing the amino
      acid composition in cell culture and fermentation broth media is important
      because deficiencies in these nutrients can reduce desired yields or alter final
      product quality. Anion-exchange (AE) chromatography using sodium hydroxide (NaOH)
      and sodium acetate gradients, coupled with integrated pulsed amperometric
      detection (IPAD), determines amino acids without sample derivatization. AE-IPAD
      also detects carbohydrates, glycols, and sugar alcohols. The presence of these
      compounds, often at high concentrations in cell culture and fermentation broth
      media, can complicate amino acid determinations. To determine whether these
      samples can be analyzed without sample preparation, we studied the effects of
      altering and extending the initial NaOH eluent concentration on the retention of
      42 different carbohydrates and related compounds, 30 amino acids and related
      compounds, and 3 additional compounds. We found that carbohydrate retention is
      impacted in a manner different from that of amino acid retention by a change in
      [NaOH]. We used this selectivity difference to design amino acid determinations
      of diluted cell culture and fermentation broth media, including Bacto yeast
      extract-peptone-dextrose (yeast culture medium) broth, Luria-Bertani (bacterial
      culture medium) broth, and minimal essential medium and serum-free protein-free
      hybridoma medium (mammalian cell culture media). These media were selected as
      representatives for both prokaryotic and eukaryotic culture systems capable of
      challenging the analytical technique presented in this paper. Glucose up to 10mM
      (0.2%, w/w) did not interfere with the chromatography, or decrease recovery
      greater than 20%, for the common amino acids arginine, lysine, alanine,
      threonine, glycine, valine, serine, proline, isoleucine, leucine, methionine,
      histidine, phenylalanine, glutamate, aspartate, cystine, and tyrosine.

PMID- 14654043
TI  - Effects of acetic acid treatment on plant chromosome structures analyzed by
      atomic force microscopy.
AB  - Acetic acid treatment has been frequently used to remove cellular contaminants
      from plant chromosome samples for structural analyses by scanning electron
      microscopy and atomic force microscopy (AFM). We evaluated the effects of various
      concentrations of acetic acid treatments on barley chromosome structures by using
      AFM. The long-term 45% acetic acid treatment significantly damaged the chromosome
      structures, although the treatment effectively removed the cellular contaminants.
      On the other hand, the treatment with 15% acetic acid could not obtain
      sufficiently clean chromosome samples and the chromosome surface structures could
      not be observed. In contrast, we obtained clean chromosome preparation without
      severe damage by using an intermediate concentration (30%) of acetic acid
      treatment. In the centromeric region, we could observe fiber structures with a
      width of 100 nm, which were composed of ca. 50-nm granules and aligned to the
      axes of chromosomes. Thus, AFM analysis of chromosomes appropriately treated with
      acetic acid will provide important insights into the organization of higher-order
      structures of plant chromosomes.

PMID- 14654044
TI  - Lucigenin and coelenterazine as superoxide probes in mitochondrial and bacterial
      membranes.
AB  - The chemiluminescent superoxide indicators lucigenin and coelenterazine were
      compared in rat liver submitochondrial particles and cytoplasmic membranes from
      Paracoccus denitrificans. Qualitative monitoring is possible with both probes,
      but quantitative work with lucigenin is hampered by its dependence on one
      electron reduction before the photon-emitting reaction. Therefore, calibration of
      measurements on complex I, capable of efficient lucigenin prereduction with
      reduced nicotinamide adenine dinucleotide, against xanthine oxidase, which in the
      presence of hypoxanthine is not able to reduce the probe to a significant rate
      compared to complex I, may give results in error by one order of magnitude.
      Coelenterazine, although susceptible of storage-dependent high background
      chemiluminescence, does not require prereduction and is thus a more reliable
      probe.

PMID- 14654045
TI  - An assay for adenosine 5'-diphosphate (ADP)-glucose pyrophosphorylase that
      measures the synthesis of radioactive ADP-glucose with glycogen synthase.
AB  - Adenosine 5'-diphosphate (ADP)-glucose pyrophosphorylase (ADP-Glc PPase)
      catalyzes the conversion of glucose 1-phosphate and adenosine 5'-triphosphate to
      ADP-glucose and pyrophosphate. We present a radioactive assay of this enzyme with
      a higher signal/noise ratio. After stopping the reaction that uses [14C]glucose 1
      phosphate as a substrate, the ADP-[14C]glucose formed as a product is converted
      to [14C]glycogen by the addition of glycogen synthase and nonradioactive glycogen
      as primer. The final product is precipitated and washed, and the radioactivity is
      measured in a scintillation counter. The [14C]glucose 1-phosphate that did not
      react is easily eliminated during the washes. We have found that this assay
      produces much lower blanks than previously described radioactive methods based on
      binding of ADP-[14C]glucose to O-(diethylaminoethyl)-cellulose paper. In
      addition, we tested the kinetic parameters for the effectors of the Escherichia
      coli ADP-Glc PPase and both assays yielded identical results. The presented
      method is more suitable for Km or S(0.5) determinations of ADP-Glc PPases having
      high apparent affinity for glucose 1-phosphate. It is possible to use a higher
      specific radioactivity to increase the sensitivity at lower concentrations of
      [14C]glucose 1-phosphate without compromising the blanks obtained at higher
      concentrations.

PMID- 14654046
TI  - Biocompatible fluorescent nanocrystals for immunolabeling of membrane proteins
      and cells.
AB  - A methodology for simple convenient preparation of bright, negatively or
      positively charged, water-soluble CdSe/ZnS core/shell nanocrystals (NCs) and
      their stabilization in aqueous solution is described. Single NCs can be detected
      using a standard epifluorescent microscope, ensuring a detection limit of one
      molecule coupled with an NC. NCs solubilized in water by DL-Cys were stabilized,
      to avoid aggregation, by poly(allylamine) and conjugated with polyclonal anti
      mouse antibodies (Abs). NC-Abs conjugates were tested in dot-blots and exhibited
      retention of binding capacity within several nanograms of antigen detected. We
      further demonstrated the advantages of NC-Abs conjugates in the immunofluorescent
      detection and three-dimensional (3D) confocal analysis of p-glycoprotein (p-gp),
      one of the main mediators of the MDR phenotype, overexpressed in the membrane of
      MCF7r breast adenocarcinoma cells. Immunolabeling of p-gp with NC-Abs conjugates
      was 4200-, 2600-, and 420-fold more resistant to photobleaching than its labeling
      with fluorescein isothiocyanate-Abs, R-phycoerythrin-Abs, and AlexaFluor488-Abs,
      respectively. The labeling of p-gp with NC-Abs conjugates was highly specific,
      and the data were used for confocal reconstruction of 3D images of the p-gp
      distribution in the MCF7r cell membrane. Finally, we demonstrated the
      applicability of NC-Abs conjugates obtained by the method described to specific
      detection of antigens in paraffin-embedded formaldehyde-fixed cancer tissue
      specimens, using immunostaining of cytokeratin in skin basal carcinoma as an
      example. We conclude that the NC-Abs conjugates may serve as easy-to-do, highly
      sensitive, photostable labels for immunofluorescent analysis, immunohistochemical
      detection, and 3D confocal studies of membrane proteins and cells.

PMID- 14654047
TI  - Advanced glycation end product ligands for the receptor for advanced glycation
      end products: biochemical characterization and formation kinetics.
AB  - Advanced glycation end products (AGEs) accumulate with age and at an accelerated
      rate in diabetes. AGEs bind cell-surface receptors including the receptor for
      advanced glycation end products (RAGE). The dependence of RAGE binding on
      specific biochemical characteristics of AGEs is currently unknown. Using
      standardized procedures and a variety of AGE measures, the present study aimed to
      characterize the AGEs that bind to RAGE and their formation kinetics in vitro. To
      produce AGEs with varying RAGE binding affinity, bovine serum albumin (BSA) AGEs
      were prepared with 0.5M glucose, fructose, or ribose at times of incubation from
      0 to 12 weeks or for up to 3 days with glycolaldehyde or glyoxylic acid. The AGE
      BSAs were characterized for RAGE binding affinity, fluorescence, absorbance,
      carbonyl content, reactive free amine content, molecular weight, pentosidine
      content, and N-epsilon-carboxymethyl lysine content. Ribose-AGEs bound RAGE with
      high affinity within 1 week of incubation in contrast to glucose- and fructose
      AGE, which required 12 and 6 weeks, respectively, to generate equivalent RAGE
      ligands (IC50=0.66, 0.93, and 1.7 microM, respectively). Over time, all of the
      measured AGE characteristics increased. However, only free amine content robustly
      correlated with RAGE binding affinity. In addition, detailed protocols for the
      generation of AGEs that reproducibly bind RAGE with high affinity were developed,
      which will allow for further study of the RAGE-AGE interaction.

PMID- 14654048
TI  - Bismuth citrate in the quantification of inorganic phosphate and its utility in
      the determination of membrane-bound phosphatases.
AB  - This paper describes a rapid and sensitive method to determine inorganic
      phosphate, even in the presence of labile organic phosphate compounds and large
      quantities of proteins. The method eliminates the use of sodium arsenite, a
      highly toxic compound, substituting bismuth citrate for it to stabilize the
      phosphomolybdic acid complex formed during the interaction of inorganic phosphate
      and molybdate reduced by ascorbic acid. This method has also been adapted to
      microplates and has been used to determine the activities of Na/K ATPase and
      alkaline phosphatase of intestinal basolateral and luminal plasma membranes.

PMID- 14654049
TI  - Detection of bacteriophage infection and prophage induction in bacterial cultures
      by means of electric DNA chips.
AB  - Infections of bacterial cultures by bacteriophages are common and serious
      problems in many biotechnological laboratories and factories. A method for
      specific, quantitative, and quick detection of phage contamination, based on the
      use of electric DNA chip is described here. Different phages of Escherichia coli
      and Bacillus subtilis were analyzed. Phage DNA was isolated from bacterial
      culture samples and detected by combination of bead-based sandwich hybridization
      with enzyme-labeled probes and detection of the enzymatic product using silicon
      chips. The assay resulted in specific signals from all four tested phages without
      significant background. Although high sensitivity was achieved in 4h assay time,
      a useful level of sensitivity (10(7)-10(8) phages) is achievable within 25 min. A
      multiplex DNA chip technique involving a mixture of probes allows for detection
      of various types of phages in one sample. These analyses confirmed the
      specificity of the assay.

PMID- 14654050
TI  - Detection of K-ras and p53 mutations in sputum samples of lung cancer patients
      using laser capture microdissection microscope and mutation analysis.
AB  - Mutations in the p53 tumor suppressor gene and the K-ras oncogene have been
      frequently found in sputum and bronchoalveolar lavage (BAL) samples of lung
      cancer patients and other patients prior to presenting clinical symptoms of lung
      cancer, suggesting that they may provide useful biomarkers for early lung cancer
      diagnosis. However, the detection of these gene mutations in sputum and BAL
      samples has been complicated by the fact that they often occur in only a small
      fraction of epithelial cells among sputum cells and, in the case of p53 gene, at
      many codons. In this study, sputum cells were collected on a filter membrane by
      sputum cytocentrifugation and morphologically analyzed. Epithelial cells were
      selectively taken by using a laser capture microdissection microscope and
      analyzed by polymerase chain reaction (PCR) and single-stranded conformational
      polymorphism (SSCP) for p53 mutations and by PCR and denaturing gradient gel
      electrophoresis (DGGE) for K-ras mutations. This method was used to analyze
      sputum of 15 Chinese women with lung cancer from Xuan Wei County, China and
      detected mutations in sputum of 7 (46.7%) patients, including 5 patients with p53
      mutations, 1 patient with a K-ras mutation, and 1 patient with K-ras and p53
      mutations. For comparison, only two of the mutations were detected by
      conventional methods. Therefore, the laser capture/mutation analysis method is
      sensitive and facilitates the detection of low-fraction mutations occurring
      throughout the p53 and K-ras genes in sputum of lung cancer patients. This method
      may be applicable to the analysis of epithelial cells from clinically normal
      sputum or BAL samples from individuals with a high risk for developing lung
      cancer.

PMID- 14654051
TI  - One-pot chemoenzymatic preparation of coenzyme A analogues.
AB  - A rapid and stoichiometric method for the synthesis of analogues of coenzyme A is
      described. The method links the enzymes pantothenate kinase, phosphopantotheine
      adenylyltransferase, and dephosphocoenzyme A kinase in vitro to generate a
      variety of CoA analogues from chemically synthesized pantothenic acid
      derivatives. The Escherichia coli CoA biosynthetic enzymes were overexpressed as
      hexa-histidine-tagged proteins, providing an abundant source of pure active
      catalysts for the reaction. The synthesis of five novel CoA derivatives is
      reported and the method is shown to be robust and tolerant of a number of
      different pantothenic acid structures, which indicates that the procedure should
      be widely applicable.

PMID- 14654052
TI  - A deoxygenation system for measuring protein phosphorescence.
AB  - An inexpensive and quick deoxygenation system for measuring protein
      phosphorescence is described. Oxygen was first reduced to less than 1 ppb from
      nitrogen or other inert gas by passing through an oxygen trap. The oxygen-free
      gas was routed through stainless steel tubing directly into the sample
      compartment of the phosphorimeter. Flexible tubing, coupled to the stainless
      steel tubing, was run through the septum of a cuvette sealed with a gray butyl
      rubber lyophilization stopper. The flexible tubing allowed for manipulation of
      the cuvette during alternate cycles of vacuuming and nitrogen equilibration.
      Utility of the system was demonstrated by measuring the phosphorescence lifetimes
      of N-acetyl-L-tryptophanamide, alkaline phosphatase, human serum albumin, and
      recombinant human serum albumin. Phosphorescence lifetimes of 2 ms for N-acetyl-L
      tryptophanamide, almost double that previously reported, were routinely achieved
      while a lifetime of 1.84 s was obtained for alkaline phosphatase, well within the
      reported range of 1.5-2s. Human serum albumin, which contains a single
      tryptophan, showed a biexponential decay with lifetimes of 4.33 and 17 ms, in
      contrast to previous reports of a biexponential decay with rates of 0.2 and 0.9
      ms. Recombinant human serum albumin was even more striking with lifetimes of 4.60
      and 68.2 ms. The data are explained based on the recently published X-ray
      crystallographic structure of human serum albumin. The simplicity and
      reproducibility of the system should make this technique practical for most
      biochemical labs.

PMID- 14654053
TI  - An amperometric glucose biosensor based on poly(o-aminophenol) and Prussian blue
      films at platinum electrode.
AB  - Prussian blue (PB), as a good catalyst for the reduction of hydrogen peroxide,
      has been combined with nonconducting poly(o-aminophenol) (POAP) film to assemble
      glucose biosensor. Compared with PB-modified enzymatic biosensor, the biosensor
      based on glucose oxidase immobilized in POAP film at PB-modified electrode shows
      much improved stability (78% remains after 30 days) in neutral medium.
      Additionally, the biosensor, at an applied potential of 0.0 V, exhibits other
      good characteristics, such as relative low detection limit (0.01 mM), short
      response time (within 5s), large current density (0.28 mA/cm2), high sensitivity
      (24 mAM(-1)cm(-2)), and good antiinterferent ability. The apparent activation
      energy of enzyme-catalyzed reaction and apparent Michaelis-Menten constant are
      34.2 KJmol(-1) and 10.5 mM, respectively. In addition, effects of temperature,
      applied potential used in the determination, pH value of the detection solution,
      and electroactive interferents on the amperometric response of the sensor were
      investigated and are discussed.

PMID- 14654054
TI  - A capillary gas chromatography/mass spectrometric method for the quantification
      of hydroxysteroids in human plasma.
AB  - A specific and sensitive methodology for the quantitative determination of
      hydroxysteroids dehydroepiandrosterone and pregnenolone and their main
      metabolites in human plasma is described. Hydroxysteroids were extracted using
      methanol and steroids were further separated by reverse-phase high-performance
      liquid chromatography, allowing for minimization of the possible chromatographic
      interferences. Eluted fractions were collected, pooled, and analyzed by gas
      chromatography-mass spectrometry as trimethylsilyl ether derivatives. The
      quantification was performed with single-ion monitoring of the highly abundant
      m/z 129 or m/z 358 fragments. The combination of the chromatographic
      characteristics to the specific fragments ensured the selectivity and specificity
      of the method. Under these conditions the method was linear (typical R2 is
      superior to 0.98 for all hydroxysteroids studied) over the concentration range of
      2 x 10(-9) to 10(-6)M with good precision and accuracy.

PMID- 14654055
TI  - Synthesis of R and S tritiated reduced beta-nicotinamide adenine dinucleotide 2'
      phosphate.
AB  - Nicotinamides are ubiquitous cofactors used by many biological systems as redox
      agents. Stereospecifically labeled cofactors are useful in many studies of
      nicotinamide-dependent enzymes. Enzyme-directed synthesis of these cofactors is
      rather common but their stability imposes significant challenges on yield,
      purity, and preservation. This paper presents the stereospecific synthesis of
      reduced R- and S-[4-3H] beta-nicotinamide adenine dinucleotide 2' phosphate
      (NADPH). The method of Valera et al. [Biochem. Biophys. Res. Commun. 148 (1987)
      515] was modified to a synthetic procedure that produces both isotopic
      diastereomers within 2h with an improved yield of 75-90% after purification and
      lyophilization. In the synthesis, [4-3H]NADP+ was generated as an intermediate
      (which can be isolated if desired). The specific radioactivities reported here
      are 2.7 and 1.1 Ci/mmol for the S and R diastereomers, respectively. Specific
      radioactivities ranging from carrier-free to trace labeling can be achieved with
      a minor change to the procedure.

PMID- 14654056
TI  - Cross-linking approach to affinity capture of protein complexes from chaotrope
      solubilized cell lysates.
AB  - Affinity capture methods are widely used for isolation and analysis of protein
      complexes. Short peptide tags fused to the protein of interest normally
      facilitate straightforward purification and detection of interacting proteins. We
      investigated the suitability of applying C-terminally hexahistidine-tagged
      interleukin-12 (IL-12) alpha- and beta-chains as "bait" proteins for cocapturing
      novel binding partners using heterologous recombinant human embryonic kidney-293
      (HEK-293) cell lines. The beta-chain, but not the alpha-chain, extracted from
      cell lysates was capable of binding to the Ni(2+)-nitrilotriacetic acid affinity
      resin under nondenaturing conditions. Retention of the alpha-chain on this matrix
      was dependent on treatment of cell lysates with high concentrations of chaotropes
      such as urea. Since under these conditions any noncovalent protein associations
      are destroyed, prior cross-linking of proteins interacting with the alpha-chain
      in intact cells was required. The use of the thiol-cleavable cross-linker 3,3'
      dithiobis(succinimidyl proprionate) facilitated dissociation of alpha-chain
      binding proteins by means of dithiothreitol following purification. Using this
      approach we were able to demonstrate a strong interaction between the endoplasmic
      reticulum chaperone calreticulin (CRT) and the IL-12 alpha-chain that was
      confirmed in a reciprocal anti-CRT immunoprecipitation assay. The assay presented
      here provides a simple approach to exposing concealed hexahistidine tags while
      retaining native noncovalent protein interactions and should be generally
      applicable in a range of pull-down or affinity capture methods aiming at analysis
      of protein complexes.

PMID- 14654057
TI  - Real-time genotyping with oligonucleotide probes containing locked nucleic acids.
AB  - Oligonucleotide probes containing locked nucleic acid (LNA) hybridize to
      complementary single-stranded target DNA sequences with an increased affinity
      compared to oligonucleotide DNA probes. As a consequence of the incorporation of
      LNA residues into the oligonucleotide sequence, the melting temperature of the
      oligonucleotide increases considerably, thus allowing the successful use of
      shorter LNA probes as allele-specific tools in genotyping assays. In this
      article, we report the use of probes containing LNA residues for the development
      of qualitative fluorescent multiplex assays for the detection of single
      nucleotide polymorphisms (SNPs) in real-time polymerase chain reaction using the
      5'-nuclease detection assay. We developed two applications that show the improved
      specificity of LNA probes in assays for allelic discrimination. The first
      application is a four-color 5'-nuclease assay for the detection of SNPs for two
      of the most common genetic factors involved in thrombotic risk, factor V Leiden
      and prothrombin G20210A. The second application is a two-color assay for the
      specific detection of the A-to-T tranversion in codon 6 of the beta-globin gene,
      responsible for sickle cell anemia. Both real-time genotyping assays were
      evaluated by comparing the performance of our method to that of a reference
      method and in both cases, we found a 100% concordance. This approach will be
      useful for research and molecular diagnostic laboratories in situations in which
      the specificity provided by oligonucleotide DNA probes is insufficient to
      discriminate between two DNA sequences that differ by only one nucleotide.

PMID- 14654058
TI  - Cardiac ischemia/reperfusion, aging, and redox-dependent alterations in
      mitochondrial function.

PMID- 14654059
TI  - Identification and quantification of free radicals during myocardial ischemia and
      reperfusion using electron paramagnetic resonance spectroscopy.
AB  - There is general agreement that free radicals are involved in reperfusion injury.
      Electron paramagnetic resonance (EPR) spectroscopy can be considered as the more
      suitable technique to directly measure and characterize free radical generation
      during myocardial ischemia and reperfusion. There are essentially two approaches
      used in the detection of unstable reactive species: freezing technique and spin
      traps. The detection of secondary free radicals or ascorbyl free radicals during
      reperfusion might provide an index of oxidative stress. Spin trapping can also
      characterize nitric oxide. EPR spectroscopy can provide important data regarding
      redox state and free radical metabolism but ideally, the spin traps must not
      interfere with cell or organism function.

PMID- 14654060
TI  - Oxidative stress in cardiovascular disease: myth or fact?
AB  - Oxidative stress is a mechanism with a central role in the pathogenesis of
      atherosclerosis, cancer, and other chronic diseases. It also plays a major role
      in the aging process. Ischemic heart disease is perhaps the human condition in
      which the role of oxidative stress has been investigated in more detail: reactive
      oxygen species and consequent expression of oxidative damage have been
      demonstrated during post-ischemic reperfusion in humans and the protective role
      of antioxidants has been validated in several experimental studies addressing the
      pathophysiology of acute ischemia. Although an impressive bulk of experimental
      studies substantiate the role of oxidative stress in the progression of the
      damage induced by acute ischemia, not a single pathophysiologic achievement has
      had a significant impact on the treatment of patients and randomized, controlled
      clinical trials, both in primary and secondary prevention, have failed to prove
      the efficacy of antioxidants in the treatment of ischemic cardiovascular disease.
      This dichotomy, between the experimental data and the lack of impact in the
      clinical setting, needs to be deeply investigated: certainly, the
      pathophysiologic grounds of oxidative stress do maintain their validity but the
      concepts of the determinants of oxidative damage should be critically revised. In
      this regard, the role of intermediate metabolism during myocardial ischemia
      together with the cellular redox state might represent a promising interpretative
      key.

PMID- 14654061
TI  - Antioxidants in myocardial ischemia-reperfusion injury: therapeutic potential and
      basic mechanisms.
AB  - Oxidative stress is a constant threat to all living organisms and an immense
      repertoire of cellular defense systems is being employed by most pro- and
      eukaryotic systems to eliminate or to attenuate oxidative stress. Ischemia and
      reperfusion is characterized by both a significant oxidative stress and
      characteristic changes in the antioxidant defense. By focusing on this
      antioxidant response of the cardiovascular system in the setting of ischemia
      reperfusion injury, the aim of this review was threefold. First, based on recent
      animal experiments and clinical studies we shall discuss how endogenous
      antioxidants respond to oxidative stress during ischemia-reperfusion injury and
      highlight the results of recent trials on the ability of antioxidants to modulate
      ischemia-reperfusion injury. In this aspect, we will particularly focus on the
      emerging concept that various lines of antioxidant defenses do not act
      individually but are linked to each other in a systematic relationship as part of
      an antioxidant network. It is well known that enzymatic mechanisms are important
      components of the endogenous antioxidant repertoire; however, the relative
      importance of the different enzyme systems and isoforms has been much debated.
      The second part will focus on recent suggestions attributing a potentially key
      role of mitochondrial MnSOD in cardiac ischemia-reperfusion injury. Finally, the
      third part of the review will critically examine how endogenous antioxidants
      might regulate the complex signal transduction pathways of cellular activation
      with particular attention to the NF-kappaB and MAPK systems that appears to
      determine outcome of injury, survival, and adaptation.

PMID- 14654062
TI  - Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection.
AB  - ATP-sensitive potassium channels allow for the coupling of membrane potential to
      cellular metabolic status. Two K(ATP) channel subtypes coexist in the myocardium
      with one subtype located in the sarcolemma membrane and the other in the inner
      membrane of the mitochondria. The ATP-sensitive potassium channels can be
      pharmacologically modulated by a family of structurally diverse agents of varied
      potency and selectivity, collectively known as potassium channel openers and
      blockers. Sufficient evidence exists to indicate that the ATP-sensitive potassium
      channels and in particular the mitochondrial ATP-sensitive potassium channels
      play an important role both as a trigger and an effector in surgical
      cardioprotection. In this review, the biochemistry and specificity of the ATP
      sensitive potassium channels is examined in relation to surgical
      cardioprotection.

PMID- 14654063
TI  - Opposing roles of delta and epsilonPKC in cardiac ischemia and reperfusion:
      targeting the apoptotic machinery.
AB  - Heart attacks, or acute myocardial infarctions (AMI), affect more than one
      million people in the US every year. The damage that occurs to the heart by AMI
      is often permanent and as a result, the morbidity and mortality rates of patients
      that experience AMIs continue to be high. Consequently, AMI patients are at
      significantly increased risks for future myocardial infarctions, decreased heart
      function, heart failure, and death [Heart and Stroke statistical update. In
      American Heart Association (2002) 4]. In this review, we discuss the events that
      lead to cardiac damage by AMI. Specifically, we discuss the current understanding
      of the role of ischemic damage vs. reperfusion damage, which is induced by the
      return of blood, oxygen, and nutrients to the organ. We also discuss the role of
      apoptosis and necrosis in cardiac damage, the means to protect the heart from
      damage by ischemia and reperfusion, and the role of protein kinase C in these
      processes.

PMID- 14654064
TI  - Endothelial dysfunction in acute and chronic coronary syndromes: evidence for a
      pathogenetic role of oxidative stress.
AB  - The past two decades have highlighted the pivotal role of the endothelium in
      preserving vascular homeostasis. Among others, nitric oxide (NO) is currently
      believed to be the main component responsible for endothelium dependent
      vasorelaxation and therefore for endothelial function integrity. Reduced NO
      bioavailability causes the so-called "endothelial dysfunction," which seems to be
      the common molecular disorder comprising stable atherosclerotic narrowing lesions
      or acute plaque rupture causing unstable angina or myocardial infarction.
      Compelling evidence is accumulating, stressing the role of oxidative stress in
      causing reduced NO bioavailability and subsequently endothelial dysfunction (ED).
      More recently, the role of endothelial cell (EC) apoptosis as a possible final
      stage of ED and plaque activation has been suggested. In vitro and in vivo
      evidence suggests a role of oxidative stress also as a putative mechanism finally
      leading to plaque denudation and activation through increased EC apoptosis. Thus,
      oxidative stress, irrespective of atherosclerotic disease stages, seems to
      represent a key phenomenon in vascular disease progression and possible
      prevention.

PMID- 14654065
TI  - Cytochrome P450: major player in reperfusion injury.
AB  - While attention has historically focused on mitochondria as the primary source of
      ROS in myocardial ischemia/reperfusion injury, recent evidence has implicated
      cytochrome P450 monooxygenases (CYPs) as a significant factor. CYPs represent a
      large family of enzymes that catalyze the oxidation of endogenous and exogenous
      compounds. They catalyze arachidonic acid oxidation to a variety of biologically
      active eicosanoids that regulate ion channels and protein kinases, with effects
      on vasomotor tone and cardiac inotropy. They also represent a significant source
      of reactive oxygen species that may target cellular homeostatic mechanisms and
      mitochondria. In this review, we will consider the contribution of cytochrome
      P450 enzymes to reperfusion injury and will speculate on whether the mechanism of
      injury is due to CYP-mediated ROS production or arachidonic acid metabolites.

PMID- 14654066
TI  - Age-related changes of cardiac gene expression following myocardial
      ischemia/reperfusion.
AB  - Young and old (4 and 25 months of age, respectively) Fisher 344/Brown Norway
      hybrid female rats were subjected to four 3 min episodes of ischemia separated by
      5 min of reperfusion. Corresponding open-chest sham-operated groups received 32
      min of no intervention. All rats were allowed to recover, and 24h later hearts
      were removed and frozen in liquid nitrogen. Global gene profiling in the ischemic
      and the non-ischemic areas and in the sham-operated hearts as well was carried
      out by using Affymetrix Gene Chips. Young ischemic hearts demonstrated down
      regulation of gene expression associated with early-remodeling including down
      regulation of tissue inhibitor of metalloproteinase 1, decorin, collagen,
      tropoelastin, and fibulin, as well as decreases in hypertrophy-related
      transcripts. In contrast, old hearts showed a unique injury-related response,
      which included up-regulation of mRNAs for proteins associated with hypertrophy or
      apoptosis (including H36-alpha7 integrin, alpha-actin, tubulin, filamin,
      connective tissue growth factor, calcineurin, serine protease, and apoptosis
      inducing factor). These injury-related changes in gene expression could in part
      explain increased gravity of outcomes of ischemia and myocardial infarction in
      elderly hearts.

PMID- 14654067
TI  - Mitochondrial membrane potentials in ischemic hearts.
AB  - Excised rat hearts were perfused isovolumically and then made globally ischemic
      for times varying from 0 to 70 min followed by 50 min of reperfusion. In situ
      mitochondrial electrical potential gradients (Deltapsi(m)) were measured during
      reperfusion using the lipophilic cation, 3H-tetraphenylphosphonium. Therefore, it
      was possible to measure the relationships between mechanical performance,
      Deltapsi(m), and high energy phosphates as a function of time of ischemia. The
      absolute value of Deltapsi(m) remained constant and then dropped sharply in
      parallel with mechanical performance after 35 min of ischemia. Eliminating Ca2+
      from the reperfusate medium did not preserve Deltapsi(m) nor increase high energy
      phosphates during the recovery period. An inhibitor of the mitochondrial
      permeability transition, cyclosporin A, delayed the fall in Deltapsi(m) but did
      not eliminate it. The data suggest that the mitochondrial permeability transition
      plays a role in ischemic cell death but is not triggered by influx of Ca2+
      through the plasma membrane.

PMID- 14654068
TI  - Ischemia-reperfusion injury in the aged heart: role of mitochondria.
AB  - The aged heart sustains greater injury during ischemia and reperfusion compared
      to the adult heart. Aging decreases oxidative phosphorylation and the activity of
      complexes III and IV only in interfibrillar mitochondria (IFM) that reside among
      the myofibrils, whereas subsarcolemmal mitochondria (SSM), located beneath the
      plasma membrane, remain unaltered. The peptide subunit composition of complexes
      III and IV is intact in aging. The aging defect in complex IV is in the inner
      membrane lipid environment. The defect in complex III is within the ubiquinol
      binding site of the cytochrome b subunit. Following ischemia, in the aged heart
      both SSM and IFM sustain additional decreases in complex III and complex IV
      activity. In contrast to the aging defect, with ischemia the subunits of complex
      IV appear to be damaged. Ischemia inactivates the iron-sulfur peptide subunit in
      complex III. Mitochondria are the major source of the reactive oxygen species
      that are generated during myocardial ischemia. Complex III is the major site of
      mitochondrial oxyradical production during ischemia in the adult heart. The role
      of complex III in the oxidative damage sustained by the aged heart during
      ischemia, as well as the potential contribution of aging defects in electron
      transport to ischemic damage in the aged heart, deserves further study. We
      propose that following ischemic damage to the electron transport chain, the
      production and release of reactive oxygen species increases from mitochondria in
      the aged heart, leading to additional damage during reperfusion.

PMID- 14654069
TI  - Mitochondria respiration and susceptibility to ischemia-reperfusion injury in
      diabetic hearts.
AB  - Cardiovascular complications are the primary cause of death for diabetic
      patients. Clinical and experimental observation has showed the development of
      dysfunctional cardiomyopathy as one of the main complications of diabetes.
      Whether the cardiomyopathy results from an increased susceptibility of cardiac
      tissue to ischemic insult or from a specific functional defect of cardiac
      mitochondria is a controversial issue. The investigation of possible functional
      defect in cardiac mitochondria from diabetic rats indicates a decline in state 3
      respiration only in animals presenting a marked decrease in body weight.
      Mitochondria from rats presenting a level of hyperglycemia similar to diabetic
      animals but not the marked weight loss typical of the latter group show no
      decline in state 3 respiration, the values being indistinguishable from those of
      control mitochondria. Mitochondria from hyperglycemic rats, however, show a 15
      20% increase in state 4 oxygen consumption but only when glutamate is used as
      energetic substrate, as compared to a 40-50% increase in state 4 respiration in
      mitochondria from diabetic rats under similar experimental conditions. This
      phenomenon is unrelated to diabetes duration, as it is observed at 2 as well as 8
      weeks after diabetes onset. Taken together, these data argue against
      hyperglycemia per se being a direct cause of the decline in state 3 oxygen
      consumption observed in cardiac mitochondria of type-I diabetic rats and indicate
      that differences exist in cardiac mitochondrial function in rats generically
      labeled as diabetic. These differences can contribute to explain discrepancies in
      experimental results reported by various groups in the field and provide an
      additional parameter to be taken into consideration in evaluating the varying
      sensitivity of diabetic hearts to ischemia-reperfusion injury.

PMID- 14654070
TI  - Preconditioning potentiates redox signaling and converts death signal into
      survival signal.
AB  - Reactive oxygen species (ROS) play a crucial role in the pathophysiology of
      ischemic heart disease by causing cardiac dysfunction and cell death. Several
      redox-sensitive anti- and pro-apoptotic transcription factors including NFkappaB
      and AP-1 progressively and steadily increase in the heart as a function of the
      duration of ischemia and reperfusion. When the heart is preconditioned to
      ischemic stress by repeated short-term ischemia and reperfusion, NFkappaB remains
      high while AP-1 is lowered to almost baseline value. The anti-apoptotic gene Bcl
      2 is downregulated in the ischemic/reperfused heart, while it is upregulated in
      the adapted myocardium. Cardioprotective abilities of the preconditioning are
      abolished when heart is pre-perfused with N-acetyl cysteine, a scavenger for ROS,
      suggesting the role of ROS in redox signaling. Mammalian heart is protected by
      several defense systems which include among others, redox-regulated protein,
      thioredoxin. Reperfusion of ischemic myocardium results in the downregulation of
      thioredoxin 1 (Trx 1) expression, which was upregulated in the preconditioned
      myocardium. The increased expression of Trx 1 is completely blocked with an
      inhibitor of Trx 1, CDDP, which also abolished cardioprotection afforded by
      ischemic adaptation. The cardioprotective role of Trx 1 is confirmed further with
      transgenic mouse hearts overexpressing Trx 1. The Trx 1 mouse hearts displayed
      significantly improved post-ischemic ventricular recovery and reduced myocardial
      infarct size and apoptosis as compared to the corresponding wild-type mouse
      hearts. Taken together, preconditioning appears to potentiate redox signaling,
      which converts the "death signal" into "survival signal."

PMID- 14654071
TI  - Monitoring treatment efficiency in MDS at the molecular level; possibilities now
      and in the future.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow (BM)
      diseases. MDS patients suffer from bone marrow failure because of the expansion
      of a malignant clone, resulting in abnormal differentiation of blood cells and
      severe pancytopenias. MDS patients have a high propensity for the development of
      acute myeloid leukemia (AML). During the last few years it has become
      increasingly clear that MDS is a stem cell disease. Two methods have generally
      been used to study the clonal origin of MDS bone marrow cells. First, the
      combination of fluorescent in situ hybridization (FISH) in combination with cell
      sorting has been used to study MDS specific numerical chromosomal aberrations in
      various cell types. Secondly, the determination of the X-chromosome inactivation
      patterns (XCIP) in different cell types of female MDS patients has been used to
      study clonality irrespective of the presence of a disease-specific marker. Both
      techniques have also been used to monitor treatment efficiency. Both methods
      showed that a molecular remission occurred in approximately half of the patients
      who achieved complete clinical remission after intensive antileukemic treatment,
      depending on the study and the type of treatment. In case of cytogenetic analysis
      this proved to be of prognostic significance. This review discusses the
      advantages and disadvantages of both techniques for the determination of
      clonality at diagnosis as well as for the assessment of treatment efficiency in
      past and in ongoing clinical trials. Future directions and possibilities for
      further research are also discussed.

PMID- 14654072
TI  - Inhibition of cyclooxygenase-2: a new targeted therapy for B-cell lymphoma?
AB  - The purpose of this editorial is to highlight the findings reported herein in the
      paper by Wun et al. on the connection between expression of the cyclooxygenase-2
      (COX-2) enzyme and B-cell lymphoma [Leuk. Res., in press]. We will first briefly
      review key aspects of the COX-2 enzyme, the newly discovered prostaglandin (PG)
      synthases and their PG products, and their roles both in inflammation and in the
      pathogenesis of cancer. Having placed the COX pathway in this context, the
      discussion will then return to the provocative findings of Wun et al. [Leuk.
      Res., 28, 2004].

PMID- 14654073
TI  - Cladribine activity in systemic mast cell disease: application of biochemistry in
      the modern era of molecular biology.

PMID- 14654074
TI  - Non-treatment-related chronic myeloid leukemia as a second malignancy.
AB  - The characteristics of the very rare non-treatment-related chronic myeloid
      leukemia (nTr-CML) cases have never before been analyzed. The literature up to
      December 2002 was screened using the Medline database to identify cases of Tr-CML
      and nTr-CML. We considered five cases with nTr-CML identified among 270 newly
      diagnosed CML at our Department. Our report thus considers nine cases with nTr
      CML compared to 77 affected by Tr-CML as a secondary neoplasm. The median age at
      the appearance of the first tumor was higher in nTr-CML patients compared to that
      of the Tr-CML group (P<0.0001). The median age at CML diagnosis was significantly
      higher in the nTr-CML than in the Tr-CML group (P<0.0001). The proportion of
      hematological malignancies as first tumor type was not different in the two
      groups (44% in nTr-CML versus 56% in Tr-CML). Our study underlines that nTr-CML
      as a second malignancy is a rare entity associated with elderly age.

PMID- 14654075
TI  - Lack of KIT or FMS internal tandem duplications but co-expression with ligands in
      AML.
AB  - KIT and FMS, members of the class III receptor tyrosine kinase family, are
      expressed on normal hematopoietic cells and have important roles in normal
      hematopoiesis. FLT3 is also a member of the class III receptor tyrosine kinase
      family and plays important role in hematopoietic stem/progenitor cells, NK, and
      dendritic cells. Recently, internal tandem duplication (ITDs) mutations have been
      found in the juxtamembrane (JM) region of FLT3 receptor expressed by patients
      with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The
      mutations result in the constitutive dimerization and activation of the receptor,
      contributing to leukemic transformation. KIT and FMS are also frequently
      expressed in AML and are closely related to FLT3. Thus, similar ITD mutations
      could also occur in the KIT and/or FMS gene of patients with AML. To explore this
      possibility, 13 human leukemia-lymphoma cell lines and 44 AML patient samples
      were examined by reverse transcription-polymerase chain reaction (RT-PCR) for the
      presence of ITD mutations in the JM region of the KIT or FMS receptor. None of
      the 13 human leukemia-lymphoma cell lines or 44 AML primary bone marrow samples
      express ITDs in either KIT or FMS in the JM region that is involved in FLT3
      mutations. The 13 cell lines and 44 AML samples were also examined for the
      possible co-expression of KIT and/or FMS receptors with their respective ligands,
      as we have seen for FLT3 and its ligand, FL. This co-expression could contribute
      to leukemic transformation through autocrine, paracrine, or intracrine activation
      mechanisms. And 6/13 cell lines and 27/44 primary AML samples exhibit co
      expression of the KIT receptor and ligand (SCF) while 10/13 cell lines and 35/44
      primary AML samples exhibit co-expression of the FMS receptor and ligand (CSF-1).
      Therefore, while ITD mutations were not found, the findings of co-expression of
      KIT and/or FMS with their respective ligands implies these receptors might
      contribute to leukemogenesis in some patients with AML through autocrine,
      paracrine, or intracrine interactive stimulation.

PMID- 14654076
TI  - Treatment of systemic mast cell disease with 2-chlorodeoxyadenosine.
AB  - We used three to six courses of 2-chlorodeoxyadenosine (2-CdA) (2-h infusion at
      0.14 mg/kg per day x 5 days) given over a period of 3-36 months to treat four
      patients with aggressive systemic mast cell disease (SMCD) that was resistant to
      interferon-alpha (IFN-alpha). Treatment with 2-CdA resulted in a major response
      in two patients and a good partial response in one other patient (75% overall
      response). Treatment was well tolerated and duration of remission in responding
      patients ranges from 2 months to 4+ years since the completion of treatment with
      2-CdA.

PMID- 14654077
TI  - Immature B cell malignancies synthesize VEGF, VEGFR-1 (Flt-1) and VEGFR-2 (KDR).
AB  - Expression of VEGF and VEGFR support a role for angiogenic pathways in the
      pathogenesis of some hematological malignances. Our goal was to determine if
      expression of these angiogenic molecules also extend to childhood precursor B
      cell acute lymphoblastic leukemia (pre-B ALL). We now show that transcripts of
      VEGF, and its receptors VEGFR-1 and VEGFR-2 are concomitantly expressed in both
      ALL cell lines and primary pre-B ALL. Western blot and ELISA consistently
      detected VEGF protein in the supernatants of the cell lines. Similarly, VEGFR-1
      and VEGFR-2 proteins are also detectable by FACS analysis. Interestingly, the
      expression of the receptors in immature B cells is limited to the intra
      cytoplasmic compartment and may suggest either internalization of the receptors
      or a block in trafficking of the receptor to the surface.

PMID- 14654078
TI  - Oral fludarabine has significant activity in patients with previously untreated
      chronic lymphocytic leukemia, and leads to increased STAT1 levels in vivo.
AB  - Fifteen patients with previously untreated chronic lymphocytic leukemia (CLL)
      were treated with oral fludarabine. Toxicities were mainly hematologic, and the
      response rate was 80%. To assess the effect of fludarabine on the transcription
      factor STAT1, blood samples obtained on study entry were treated in vitro with
      fludarabine for 24 h, and the majority of samples displayed an expected decrease
      in STAT1. To determine whether similar changes occurred in vivo, we developed a
      flow cytometric assay to quantitate STAT1 levels. On completion of fludarabine
      cycle 1, CLL cells showed increased STAT1 in the majority of patients, in
      contrast to the in vitro findings. This may reflect a survival advantage for
      cells that express high levels of STAT1. In conclusion, oral fludarabine is
      highly active and merits further investigation in previously untreated patients
      with CLL. Larger studies are indicated to determine optimal timing of STAT1
      assessment, and if changes in STAT1 represent an in vivo indicator of response to
      purine analog therapy.

PMID- 14654079
TI  - MmTRA1b/phospholipid scramblase 1 gene expression is a new prognostic factor for
      acute myelogenous leukemia.
AB  - We previously found that expression of the Mm-1 cell-derived transplantability
      associated gene 1b (MmTRA1b)/phospholipid scramblase 1 gene was markedly induced
      during the granulocytic differentiation of human myeloid leukemia cells. To
      evaluate the role of MmTRA1b expression in human myeloid leukemia, we
      investigated the relative levels of MmTRA1b transcripts in 81 patients with acute
      myelogenous leukemia (AML) by the reverse transcriptase polymerase chain
      reaction. The expression of MmTRA1b in AML-M1, -M5a and -M5b was significantly
      lower than that in normal bone marrow cells. The levels of MmTRA1b expression in
      AML-M2 and -M4 varied among patients. Higher MmTRA1b mRNA levels were associated
      with significantly longer overall survival in AML, especially in AML-M4 patients,
      independent of chromosomal aberrations such as t(8;21) and inv(16). The present
      results suggest that the MmTRA1b mRNA level is a new prognostic factor for AML,
      especially the AML-M4 subtype.

PMID- 14654080
TI  - Interleukin 4 production by peripheral blood lymphocytes in patients with
      classical Hodgkin lymphoma.
AB  - Although the production of interleukin (IL) 2 and interferon (IFN) gamma by
      peripheral blood lymphocytes in patients with Hodgkin lymphoma (HL) is well
      documented, the synthesis of IL4 has not been investigated before. The present
      study examines the production of IL4 by 2-day phytohaemaglutinin (PHA)-stimulated
      peripheral blood (PB) cells in HL and correlates the cytokine levels with the
      proportion of the different T-cell sub-populations. We observed a significant
      increase in the mean level of production of IL4 in patients with HL when compared
      with normal controls. The increased amount of IL4 in patients with HL correlated
      significantly with the proportion of the CD3(+)CD8(+) cells but not with
      CD3(+)CD4(+). The intensity of cytoplasmic IL4 (expressed as relative median
      fluorescence (RMF)) was significantly higher in the CD3(+)CD8(+) cells of the
      patients with HL compared with the CD3(+)CD4(+) sub-population, or with the
      normal CD3(+)CD8(+) cells and correlated with the levels of IL4 release in
      culture supernatants. In conclusion, there is increased production of IL4 by PHA
      activated PB lymphocytes in HL. The CD3(+)CD8(+) T-cell population appears to be
      responsible for this increased synthesis.

PMID- 14654081
TI  - Novel regimen for the treatment of juvenile myelomonocytic leukemia (JMML).
AB  - The effective treatment for juvenile myelomonocytic leukemia (JMML) patients
      lacking access to stem cell transplantation remains unavailable. Here, we
      describe a promising result obtained with novel regimen comprised of a
      combination of chemotherapy and differentiation therapy. Five patients diagnosed
      as JMML were treated with a standard regimen (cytosine arabinoside (Ara-C)
      100mg/m(2) per day continuous infusion (days 0-6), etoposide 100mg/m(2) per day
      (days 0-4), vincristine 1.5mg/m(2) per d (day 9) and isotretinoin 75-100mg/m(2)
      per day (days 10-20)). All patients responded to the standard regimen. Three of
      the five were later treated with salvage a regimen (Ara-C 100mg/m(2) per day
      continuous infusion (days 0-4), etoposide 100mg/m(2) per day (days 0-4) and Ara-C
      15mg/m(2) per day SC (days 6-15)) when immature myeloid cells reappeared in the
      peripheral blood, the spleen increased or blast crisis occurred. Immature myeloid
      cells disappeared again after one cycle of salvage regimen in all patients. All
      patients are alive now with a median follow up duration of 27 months (8-69
      months). Although the number of patients enrolled was limited, the standard and
      salvage regimens were found to be safe and effective alternatives for JMML
      patients without a matched donor. These regimens also could be used safely before
      stem cell transplantation.

PMID- 14654082
TI  - Hidden chromosomal aberrations are rare in primary myelodysplastic syndromes with
      evolution to acute myeloid leukaemia and normal cytogenetics.
AB  - In myelodysplastic syndromes (MDS) a normal karyotype by cytogenetic analysis
      (CA) corresponds to a low cytogenetic risk for acute myeloid leukaemia (AML)
      evolution, a subset of patients however develops AML. We evaluated the use of
      interphase fluorescence in situ hybridisation (I-FISH) in 31 patients with
      evolution from primary MDS to AML and a normal CA at all stages of disease.
      Monosomy 7 was found in 4/31 cases, one patient had a terminal deletion 5q, each
      after AML evolution. The low frequency and unclear prognostic value of I-FISH
      anomalies in MDS related AML suggests that these alterations play a minor role
      for AML evolution.

PMID- 14654083
TI  - Increased cyclooxygenase-2 (COX-2): a potential role in the pathogenesis of
      lymphoma.
AB  - B cell lymphomas are a diverse group of clinicopathologic diseases with an
      increasing incidence. As with other malignancies, the accumulation of genetic
      abnormalities are required for malignant transformation of human lymphocytes.
      Cyclooxygenase-2 (COX-2) is a key biosynthetic enzyme in prostaglandin synthesis
      and has been implicated in the pathogenesis of numerous malignancies including
      colon, breast, and lung cancer. There is little data on the potential role of COX
      2 in lymphoma pathogenesis. In this study, several B lymphoma cell lines and
      primary B cells obtained from normal volunteer controls were examined for COX-2
      protein expression. Immunoblot analysis demonstrated between an approximately 2.2
      4.3-fold increase in COX-2 protein expression relative to primary B cells in all
      lymphoma cell lines examined. Increased COX-2 phosphorylation was found in the
      BJAB, BL41, and Raji cells whereas the levels in Daudi, Namalwa, and Ramos did
      not differ from that of primary B cells. Treatment with 25-100 microM celecoxib
      (CEL) resulted in decreased proliferation as measured by [3H]thymidine in all
      cell lines examined, and the effect was dose-dependent, and not significantly
      enhanced by chlorambucil (CHL). The effect of COX-2 inhibition on apoptosis in
      lymphoma cells was examined and revealed apoptotic induction of greater than 85%
      in all cell lines examined at 50 microM celecoxib. The pro-apoptotic effect was
      dose-dependent, and was not significantly enhanced by chlorambucil. Examination
      of apoptosis-related proteins by immunoblot analysis revealed levels of BCL-2,
      BCL-X(L), and Bax to be unaffected by celecoxib. In contrast, levels of Akt, MCL
      1, and phosphorylated SAP-kinase were all decreased after incubation with 50
      microM celecoxib. These findings suggest that increased COX-2 expression and
      activity, contributes to the pathogenesis of B cell lymphomas and point to a
      possible role for COX-2 inhibition in their treatment.

PMID- 14654084
TI  - Endoplasmic reticulum stress initiates apoptotic death induced by STI571
      inhibition of p210 bcr-abl tyrosine kinase.
AB  - The endoplasmic reticulum (ER) is the site where proteins destined to either
      secretion or different subcellular compartments assemble and the major storage of
      intracellular Ca(2+). The ER stress resulting from a variety of toxic insults
      leads to apoptosis. Here, we showed that the apoptotic death triggered by STI571,
      an inhibitor of the p210 bcr-abl tyrosine kinase, in murine myeloid progenitors
      transducing the p210 bcr-abl tyrosine kinase of Chronic Myeloid Leukemia (CML)
      proceeds from ER stress. The Bcl-2 dowmodulation and inactivation induced by the
      binding to its antagonist: Bad, the release of caspase 12 from the ER membranes
      in its active form and of Ca(2+) from the ER pool addressed towards ER a sensor
      of STI571-induced pro-apoptotic signal.

PMID- 14654085
TI  - Identification of a S100 calcium-binding protein expressed in HL-60 cells treated
      with all-trans retinoic acid by two-dimensional electrophoresis and mass
      spectrometry.
AB  - To characterize the alteration of protein expression during tumor cell
      differentiation induced by all-trans retinoic acid (ATRA) and to understand
      downstream signaling and molecular mechanism of ATRA action, we compared the
      protein expression profiles in HL-60 cells with ATRA treatment using two
      dimensional electrophoresis (2-DE). Although many changes in protein expression
      were found in 2-DE maps, here we identified two protein spots remarkably
      expressed in the differentiated cells by nanoelectrospray ionization mass
      spectrometry and database searching. These two protein spots were found to be the
      same protein, namely S100 calcium-binding protein A9 (S100A9). Further study will
      be done to ascertain whether S100A9 plays a role in the regulation of
      differentiation or just a consequence of differentiation.

PMID- 14654086
TI  - Apoptosis of Raji cells by an anti-CD20 antibody HI47 and its fragments.

PMID- 14654087
TI  - Classification of refractory anemia.

PMID- 14654089
TI  - Regulation of stearoyl-CoA desaturases and role in metabolism.
AB  - Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the
      synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate
      (16:1). These represent the major monounsaturated fatty acids of membrane
      phospholipids, triglycerides, wax esters and cholesterol esters. The ratio of
      saturated to monounsaturated fatty acids affects phospholipid composition and
      alteration in this ratio has been implicated in a variety of disease states
      including cardiovascular disease, obesity, diabetes, neurological disease, and
      cancer. For this reason, the expression of SCD is of physiological significance
      in both normal and disease states. Several SCD gene isoforms (SCD1, SCD2, SCD3)
      exist in the mouse and one SCD isoform that is highly homologous to the mouse
      SCD1 is well characterized in human. The physiological role of each SCD isoform
      and the reason for having three or more SCD gene isoforms in the rodent genome
      are currently unknown but could be related the substrate specificities of the
      isomers and their regulation through tissue-specific expression. The recent
      studies of asebia mouse strains that have a natural mutation in the SCD1 gene and
      a mouse model with a targeted disruption of the SCD1 gene have provided clues
      concerning the role that SCD1 and its endogenous products play in the regulation
      of metabolism.

PMID- 14654090
TI  - The digestion of dietary triacylglycerols.
AB  - Dietary triacylglycerols (TAGs) are the major lipid components in the human diet
      and they are carriers of energy as well as important fatty acids. Many factors
      affect the digestion and absorption of TAGs. Evidence is accumulating that, in
      addition to the overall fatty acid profile, the TAG structure and the species
      composition are of importance when considering the nutritional effects of a
      dietary fat. There is good evidence that in addition to its short-term effects in
      the intestine on absorption of fatty acids the TAG structure also has long-term
      effects resulting from differences in the profile of absorbed fatty acids.
      Observations on the different atherogenic potential of dietary fats have given us
      a clear indication of the importance of the TAG structure for absorption of
      saturated fatty acids. In this context, one may focus on the effects of the
      structure of dietary fats as such, or one may speculate additionally on the
      possibilities of modifying the structure of fats to affect their absorption and
      the distribution of the fatty acids in the body after digestion and uptake. In
      this review we will summarize diverse aspects of TAG digestion and absorption, as
      well as the influences of the fatty acid composition and the intramolecular
      structure of dietary TAGs on their digestion and absorption.

PMID- 14654091
TI  - Enzymes of triacylglycerol synthesis and their regulation.
AB  - Since the pathways of glycerolipid biosynthesis were elucidated in the 1950's,
      considerable knowledge has been gained about the enzymes that catalyze the lipid
      biosynthetic reactions and the factors that regulate triacylglycerol
      biosynthesis. In the last few decades, in part due to advances in technology and
      the wide availability of nucleotide and amino acid sequences, we have made
      enormous strides in our understanding of these enzymes at the molecular level. In
      many cases, sequence information obtained from lipid biosynthetic enzymes of
      prokaryotes and yeast has provided the means to search the genomic and expressed
      sequence tag databases for mammalian homologs and most of the genes have now been
      identified. Surprisingly, multiple isoforms appear to catalyze the same chemical
      reactions, suggesting that each isoform may play a distinct functional role in
      the pathway of triacylglycerol and phospholipid biosynthesis. This review focuses
      on the de novo biosynthesis of triacylglycerol in eukaryotic cells, the
      isoenzymes that are involved, their subcellular locations, how they are
      regulated, and their putative individual roles in glycerolipid biosynthesis.

PMID- 14654092
TI  - Differential actions of diazepam and zolpidem in basolateral and central amygdala
      nuclei.
AB  - Benzodiazepines are among the most widely prescribed therapeutic agents, having
      anxiolytic, anticonvulsant, sedative/hypnotic, and amnestic properties (Mehta and
      Ticku, Brain Res. Rev. 29 (1999) 196). Recent research indicates that these
      disparate actions are dissociable (Nature 401 (1999) 796; Science 290 (2000) 131;
      Kralic et al., Neuropharmacology 43 (2002) 685). Behavioral studies indicate that
      the amygdala plays a critical role in the anxiolytic effect of benzodiazepines
      (Nagy et al., Neuropharmacology 18 (1979) 573; The amygdala: anxiety and
      benzodiazepines. The Amygdala: a Functional Analysis. p. 195). However, the
      neuronal substrates of this anxiolytic effect remain unclear. Our study
      characterizes the physiological response to acute application of the
      benzodiazepine diazepam and the non-benzodiazepine sedative zolpidem using whole
      cell patch recording in two discrete amygdala subnuclei. We found that acute
      application of diazepam enhances GABA(A) receptor-mediated inhibitory
      postsynaptic currents (IPSCs) with equal potency in the basolateral (BL) and
      central (Ce) amygdala subnuclei. However, zolpidem enhanced IPSCs with similar
      potency only in the BL, and was effective in the Ce only at high concentrations.
      This finding is in agreement with histochemical data regarding the localization
      of GABA(A) receptor isoforms in the amygdala (J. Comp. Neurol. 359 (1995) 154;
      Brain Res. 964 (2003) 91) and suggests that anxiolytic effects of allosteric
      modulators of the GABA(A) receptor may be further dissociated from their
      hypnotic/sedative effects.

PMID- 14654093
TI  - The effects of IDRA 21, a positive modulator of the AMPA receptor, on delayed
      matching performance by young and aged rhesus monkeys.
AB  - IDRA 21, a positive allosteric modulator of the glutamate AMPA receptor, produced
      a concentration-dependent inhibition of glutamate-induced inactivation of
      membrane currents in recombinant HEK 293 (human embryonic kidney) cells stably
      transfected with human GluR1/2 flip receptors. IDRA 21 doubled the charge
      transfer at a concentration of 70 microM, suggesting that this compound can
      facilitate excitatory neurotransmission via GluR 1/2 receptors. We next sought to
      exploit this mechanism of action by examining the drug as a potential cognition
      enhancing agent in non-human primates. Oral administration of IDRA 21 produced a
      highly significant improvement in the performance of a delayed matching-to-sample
      (DMTS) task by young adult rhesus monkeys. The pattern of task improvement over
      the dose range 0.15-10 mg/kg was maintained to 48 hr after the single dose
      administration. For sessions run after administration of the individualized Best
      Dose of IDRA 21, task accuracy for Long delay (most difficult) trials was
      increased by 34% of vehicle. Animals were randomly assigned fixed doses of IDRA
      21 to determine whether the positive mnemonic response could be maintained. The
      repeated doses were separated by 3 days, thus allowing for potential cumulative
      effects. IDRA 21 produced a gradual increase in task accuracy that was maintained
      on average above vehicle performance levels over an intermittent dosing schedule
      during a total period of 3 weeks. A separate group of aged monkeys (>20 y) were,
      as a group, impaired (during vehicle testing) in DMTS performance efficiency
      relative to the young cohort. IDRA 21 also improved task accuracy by aged rhesus
      monkeys over the same dose range, but the responses were not as robust as those
      exhibited by young animals. Aged subjects also appeared to be more individually
      sensitive to drug dose, and they exhibited shorter task latencies than did the
      young group. Despite these differences, when the individualized Best Doses were
      considered, IDRA 21 produced a robust increase in DMTS accuracy of up to 18% of
      vehicle for trials associated with Medium delay intervals. For both study groups,
      no obvious untoward effects of IDRA 21 were noted. These findings support the use
      of AMPA modulators like IDRA 21 in the treatment of cognitive/memory disorders,
      including those associated with aging. They also indicate that the drug is
      associated with long-term effects that could limit dosing regimens to one dose
      every two or three days. The nature of the protracted mnemonic effects produced
      by the compound remains to be elucidated.

PMID- 14654094
TI  - NR2B containing NMDA receptor dependent windup of single spinal neurons.
AB  - Windup, the frequency dependent build-up of spinal neuronal responses, is
      implicated in the development of central sensitization of nociceptive pathways. N
      methyl-D-aspartate (NMDA) receptors have been shown to be involved in these
      processes but the role of various receptor subtypes at the spinal level is not
      fully understood. In our experiments, we compared the inhibitory effect of MK-801
      (a nonselective NMDA receptor antagonist, 0.01-3 mg/kg i.v.) and CI-1041 (an NR2B
      subunit specific NMDA receptor antagonist, 0.3-10 mg/kg i.v.) on the formation of
      dorsal horn neuronal windup in spinalized rats, in vivo. Both types of antagonist
      blocked windup considerably at doses not affecting the normal synaptic
      transmission. These results are in agreement with the well-documented effectivity
      of NR2B subtype selective NMDA receptor antagonists in chronic pain models and
      give the first direct evidence that spinal mechanisms are involved in this
      effect.

PMID- 14654095
TI  - Lamina-specific differences in GABA(B) autoreceptor-mediated regulation of
      spontaneous GABA release in rat entorhinal cortex.
AB  - Spontaneous synaptic inhibition plays an important role in regulating the
      excitability of cortical networks. Here we have investigated the role of GABA(B)
      autoreceptors in regulating spontaneous GABA release in the entorhinal cortex
      (EC), a region associated with temporal lobe epilepsies. We have previously shown
      that the level of spontaneous inhibition in superficial layers of the EC is much
      greater than that seen in deeper layers. In the present study, using
      intracellular and whole cell patch clamp recordings in rat EC slices, we have
      demonstrated that evoked GABA responses are controlled by feedback inhibition via
      GABA(B) autoreceptors. Furthermore, recordings of spontaneous, activity
      independent inhibitory postsynaptic currents in layer II and layer V neurones
      showed that the GABA(B) receptor agonist, baclofen, reduced the frequency of GABA
      mediated currents indicating the presence of presynaptic GABA(B) receptors in
      both layers. Application of the antagonist, CGP55845, blocked the effects of
      baclofen and also increased the frequency of GABA-mediated events above baseline,
      but the latter effect was restricted to layer V. This demonstrates that GABA(B)
      autoreceptors are tonically activated by synaptically released GABA in layer V,
      and this may partly explain the lower level of spontaneous GABA release in the
      deep layer.

PMID- 14654096
TI  - GABA(B) receptor activation and limbic network ictogenesis.
AB  - Rat brain slices containing interconnected hippocampus and entorhinal cortex (EC)
      responded to 4-aminopyridine (50 microM) application by generating: (i) CA3
      driven interictal discharges that propagated to the EC; and (ii) N-methyl-D
      aspartic (NMDA) acid receptor-dependent ictal events originating in EC (cf. J.
      Neurosci. 17 (1997) 9308 for experiments made in brain slices). Ictal discharges
      disappeared within 1-2 h, but were re-established by cutting the Schaffer
      collaterals, which abolished CA3-driven interictal discharge propagation to EC.
      In intact slices, GABA(B) receptor activation by baclofen (5-40 microM): (i)
      depressed CA3-driven interictal activity; and (ii) disclosed non-NMDA
      glutamatergic receptor-dependent ictal discharges originating in CA3 and
      propagating to EC. These effects were reversed by the GABA(B) receptor antagonist
      CGP 35348 (0.5 mM). Application of increasing baclofen doses to slices in which
      hippocampus and EC networks were surgically isolated decreased epileptiform
      events with an IC50 that was lower in EC (0.6 microM; n = 12) than in CA3 (2.5
      microM; n = 12). Hence, under control conditions, EC ictogenesis depends on NMDA
      receptor function and is controlled by CA3-driven output activity; in contrast,
      following GABA(B) receptor activation EC excitability is depressed to a greater
      extent than CA3, which leads to non-NMDA glutamatergic receptor-mediated
      ictogenesis in CA3. We propose that GABA(B) receptor modulation may represent an
      important mechanism for setting the site of initiation, the modalities of
      propagation and the glutamatergic receptor properties of ictogenesis in the
      limbic system and, perhaps, in mesial temporal lobe epilepsy patients.

PMID- 14654097
TI  - 8-OH-DPAT as a 5-HT7 agonist: phase shifts of the circadian biological clock
      through increases in cAMP production.
AB  - Neurons in the suprachiasmatic nucleus (SCN), the site of the endogenous
      biological clock in mammals, fire spontaneously, peaking in firing rate near ZT6
      or at the midpoint of the light phase in a 12:12 light-dark cycle. In rat
      hypothalamic slices, tissue incubations with drugs can produce a shift in this
      daily rhythm, the magnitude of which is dependent upon dose and the time of
      treatment. Previous work with 8-OH-DPAT had noted its ability to produce a phase
      advance, an earlier occurrence of the peak in neuronal firing, when applied at
      ZT6. Activation of 5-HT7 receptors was thought to be responsible for the shift,
      despite the clear preference of 8-OH-DPAT for 5-HT1A sites in terms of receptor
      binding affinity. In the present work, the actions of 8-OH-DPAT in SCN slices
      were confirmed and expanded to include additional dose-response and antagonist
      treatments. By itself, 8-OH-DPAT produced a concentration-dependent phase advance
      that was sensitive to co-application with 5-HT7 antagonists (ritanserin,
      mesulergine, SB-269970), but not to 5-HT1A antagonists (WAY-100,635, UH-301).
      Assignment of the receptor mechanisms for the antagonists employed was
      accomplished in experiments measuring binding affinities and the generation of
      cAMP, the latter monitored in a HEK-293 cell line expressing the r5-HT7 receptor
      and in tissue derived from rat SCN. The results indicate that the increases
      observed in cAMP levels are small but appear to be sufficient to produce a
      pharmacological resetting of the clock pacemaker. By aiding in the identification
      of the 5-HT receptor subtype responsible for the observed phase shifts and cAMP
      changes, 8-OH-DPAT represents an important pharmacological tool for 5-HT7
      receptor activation, essentially broadening its role as the prototypical 5-HT1A
      agonist to one combining these two receptor activities.

PMID- 14654098
TI  - The sleep inducing brain lipid cis-oleamide (cOA) does not modulate serotonergic
      transmission in the CA1 pyramidal neurons of the hippocampus in vitro.
AB  - cis-Oleamide (cOA) is a novel sleep inducing brain lipid with an unknown
      mechanism of action. High affinity interactions with metabotropic 5-HT receptors
      (2A/C and 1A subtypes) in frog oocytes and expression systems have been reported,
      but functional in vitro evidence for the modulatory effect is still lacking.
      Here, we addressed the ability of cOA to modulate 5-HT-induced cellular actions
      in the CA1 neurons of the rat hippocampal slice.5-HT (0.1-100 microM)
      concentration dependently reduced the amplitude of the evoked field population
      spike (fPS), and produced a hyperpolarising shift in the resting membrane
      potential (Vr) and a drop in input resistance (R in). The effects of a low dose
      of 5-HT (3.2 microM) on fPS, Vr and R in were reversed by the specific 5-HT(1A)
      receptor antagonist WAY 100135 (10 microM). cOA (1 microM) failed to potentiate 5
      HT1A receptor mediated effects on fPS, Vr or R in. High doses of 5-HT also
      recruited both 5-HT2 and 5-HT3 receptors, causing an increase in the rate and
      amplitude of sIPSCs. cOA (1 microM), in the presence of Y 25130, failed to
      potentiate the 5-HT2 receptor induced enhancement of sIPSCs. In summary, cis
      oleamide failed to modulate metabotropic responses to exogenous 5-HT in this
      microelectrode study at concentrations well in excess of those reported to
      modulate 5-HT1A and 5-HT2A/C systems in earlier studies.

PMID- 14654099
TI  - Long-lasting behavioral sensitization to psychostimulants following p
      chloroamphetamine-induced neurotoxicity in mice.
AB  - Amphetamine analogs such as p-chloroamphetamine (PCA) cause serotonergic and
      dopaminergic neurotoxicity. The behavioral consequences and the responsiveness to
      psychostimulants following the neurotoxic insult are unclear. The present study
      was undertaken to investigate the outcome of neurotoxic and non-neurotoxic PCA
      pre-treatments on the sensitivity of Swiss Webster mice to the psychomotor
      stimulating effects of PCA, 3,4-methylenedioxymethamphetamine (MDMA) and cocaine.
      PCA (15 mg/kg x 2; i.p.) caused 37-70% depletion of dopaminergic and serotonergic
      markers in mouse brain. Saline and PCA (15 mg/kg x 2) mice were challenged on
      days 5, 12, 40 and 74 with one of the following drugs: PCA (5 mg/kg), MDMA (10
      mg/kg) and cocaine (20 mg/kg). The PCA pre-exposed mice showed marked locomotor
      sensitization from days 5-74 to all three drugs tested. The time course of the
      sensitized response coincided with the time course of the neurotoxic insult as
      determined by reduced densities of striatal dopamine transporter and frontal
      cortex serotonin transporter binding sites. A single injection of PCA (5 mg/kg)
      caused neither neurotoxicity nor sensitization to the locomotor stimulating
      effects of PCA, MDMA and cocaine. Repeated administration of a low non-neurotoxic
      dose of PCA (5 mg/kg/day; 6 days) caused a transient locomotor sensitization to
      PCA that dissipated after one month. Results of the present study suggest that
      PCA-induced serotonergic and dopaminergic neurotoxicity coincides with long
      lasting locomotor sensitization to psychostimulants. These findings may be
      relevant to the psychopathology of amphetamines-induced neurotoxicity.

PMID- 14654100
TI  - Post-pubertal adrenergic changes in rats with neonatal lesions of the ventral
      hippocampus.
AB  - Lesions of the ventral hippocampus (VH) in neonatal rats result in post-pubertal
      alterations in a number of cognitive, social and motor behaviors that bear some
      analogy to schizophrenia. Increased sensitivity to stress and psychostimulants
      and prefrontal functional changes in the lesioned animals suggest an involvement
      of the mesocorticolimbic dopamine (DA) system. DA and norepinephrine (NE)
      interact in a number of ways in the medial prefrontal cortex (mPFC) to influence
      each other's functions. In order to assess the role of adrenergic system in the
      behavioral responses of neonatal VH (nVH) lesioned animals, we first examined
      cortical and subcortical bindings of alpha-1 and alpha-2 adrenergic receptors
      using [3H]-prazosin and [3H]-rauwolscine respectively, and the norepinephrine
      transporter (NET) using [3H]-nisoxetine. Sprague-Dawley rat pups, at post-natal
      day (PD) 7, received bilateral injections of ibotenic acid in the VH and were
      sacrificed pre (PD35)- and post (PD56)-pubertally. A significant increase in [3H]
      prazosin binding was observed in the frontal and cingulate cortices of lesioned
      rats at PD56 without any significant change in the caudate putamen or nucleus
      accumbens. No significant difference was seen in [3H]-rauwolscine binding. A
      significant upregulation of NET binding was observed in subregions of the PFC and
      nucleus accumbens of PD56 lesioned rats. The functional relevance of changes in
      adrenergic markers on amphetamine-induced locomotor activity was examined by pre
      treatment of PD56 rats with prazosin, an alpha-1 receptor antagonist. Prazosin at
      doses of 1.0 or 2.0 mg/kg ip significantly reduced amphetamine-induced locomotion
      in sham but not in PD56 lesioned animals. Taken together, these results suggest
      that alterations in prefrontal alpha-1 receptors likely contribute to altered
      behavioral responses observed in post-pubertal VH lesioned rats.

PMID- 14654101
TI  - Potentiation effects of (+/-)huprine X, a new acetylcholinesterase inhibitor, on
      nicotinic receptors in rat cortical synaptosomes.
AB  - The present experiments were developed to analyze the direct and/or potentiation
      effect of (+/-)-12-amino-3-chloro-9-ethyl-6,7,10,11-tetrahydro-7,11
      methanocycloocta[b]quinoline hydrochloride ((+/-)huprine X) on nicotinic
      receptors using a synaptosomal superfusion method. (+/-)Huprine X (1 microM, 10
      microM) increased [(3)H]-ACh release only at 10 microM (46%; P < 0.001) in basal,
      but not in stimulated, conditions. This effect was completely reverted by
      mecamylamine (100 microM; MEC). Potentiation of evoked-[3H]-ACh release induced
      by ACh (1 microM) and by galantamine (GAL) 0.4 microM and physostigmine (PHY) 10
      microM (55% and 50%, respectively; P < 0.001), two well-known allosteric
      compounds, corroborate that the present experimental approach is a suitable
      method to study potentiation effects on nicotinic receptors in the central
      nervous system nerve terminals. (+/-)Huprine X potentiated the evoked-[3H]-ACh
      release induced by ACh (1 microM) by 166% and 90% (P < 0.001) at 10 microM and 30
      microM, respectively, and this effect was completely blocked by MEC (100 microM).
      In the presence of different ACh concentrations, (+/-)huprine X 10 microM
      potentiated evoked-[3H]-ACh release at low ACh concentrations, while a decrease
      in neurotransmitter release was observed at high ACh concentrations. The highest
      potentiation effect was obtained at the ACh/(+/-)huprine X concentration ratio of
      1:10, and this potentiation was observed at as low a (+/-)huprine X concentration
      as 0.1 microM (P < 0.05). While the results suggest that huprine may enhance the
      potency or effectiveness of ACh by an effect involving nicotinic receptors we
      cannot completely discard that the results could be explained by acetylcholine
      esterase inhibition.

PMID- 14654102
TI  - Galantamine prevents apoptosis induced by beta-amyloid and thapsigargin:
      involvement of nicotinic acetylcholine receptors.
AB  - Galantamine is currently used to treat Alzheimer's disease patients; it behaves
      as a mild blocker of acetylcholinesterase (AChE) and has an allosteric modulating
      action on nicotinic acetylcholine receptors (nAChRs). In this study, we observed
      that galantamine prevented cell death induced by the peptide beta-amyloid(1-40)
      and thapsigargin in the human neuroblastoma cell line SH-SY5Y, as well as in
      bovine chromaffin cells. The protective effect of galantamine was concentration
      dependent in both cell types; maximum protection was produced at 300 nM. The
      antiapoptotic effect of galantamine at 300 nM, against beta-amyloid(1-40) or
      thapsigargin-induced toxicity, was reversed by alpha-bungarotoxin. At
      neuroprotective concentrations, galantamine caused a mild and sustained elevation
      of the cytosolic concentration of calcium, [Ca2+]c, measured in single cells
      loaded with Fura-2. Incubation of the cells for 48 h with 300 nM galantamine
      doubled the density of alpha7 nicotinic receptors and tripled the expression of
      the antiapoptotic protein Bcl-2. These results strongly suggest that galantamine
      can prevent apoptotic cell death by inducing neuroprotection through a mechanism
      related to that described for nicotine, i.e. activation of nAChRs and
      upregulation of Bcl-2. These findings might explain the long-term beneficial
      effects of galantamine in patients suffering of Alzheimer's disease.

PMID- 14654103
TI  - Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence
      for CB1- and non-CB1-mediated actions.
AB  - Recent evidence indicates that the basolateral amygdala (BLA) may be involved in
      behavioural effects induced by cannabinoids. High levels of CB1 cannabinoid
      receptors have been shown in this region, where they modulate excitatory and
      inhibitory synaptic transmission. However, the neurophysiological effects of
      these opposing synaptic actions have not been investigated in vivo. To this
      purpose, single-unit extracellular recordings were performed in urethane
      anaesthetized rats in order to determine whether exogenously applied cannabinoids
      influenced the spontaneous or evoked electrical activity of neurons in the BLA.
      The effects of cannabinoids were found to be dependent on the characteristics of
      the neurons examined and on the properties of the agents used. We tested and
      compared two structurally different synthetic cannabinoid receptor agonists, the
      highly potent HU-210 (0.125-1.0 mg/kg, i.v.) and WIN55212-2 (WIN, 0.125-1.0
      mg/kg, i.v.). With a CB1 cannabinoid receptor-dependent mechanism, HU-210
      potently inhibited the firing rate of BLA interneurons whereas WIN modulated the
      discharge rate in a biphasic manner. By contrast, BLA projection neurons,
      antidromically identified from the shell of the nucleus accumbens, were
      significantly inhibited by WIN at all doses tested, while HU-210 administration
      led to less consistent effects, since only 1.0 mg/kg inhibited firing rate in the
      majority of recorded neurons. Additionally, WIN, but not HU-210, significantly
      attenuated short-latency spiking activity in BLA projection neurons evoked by
      electrical stimulation of the medial prefrontal cortex. In these neurons, WIN
      induced effects were antagonised by the non-selective cannabinoid receptor
      antagonist SR141716A and by the vanilloid receptor antagonist capsazepine, but
      not by the selective CB1 antagonist AM-251. Taken together, our findings indicate
      that the overall excitability of efferent neurons in the BLA is strongly reduced
      by WIN in a non-CB1-dependent manner. In this effect, the contribution of a novel
      cannabinoid-vanilloid-sensitive putative non-CB1 receptors, the existence of
      which was postulated in recent reports, might play a role.

PMID- 14654104
TI  - Contribution of cGMP but not peroxynitrite to negative feedback regulation of
      penile erection elicited by nitric oxide in the hippocampal formation of the rat.
AB  - We established previously that nitric oxide (NO) in the hippocampal formation
      (HF) participates actively in negative feedback regulation of penile erection.
      This study further evaluated whether this process engaged soluble guanylyl
      cyclase (sGC)/cGMP cascade or peroxynitrite in the HF. Intracavernous pressure
      (ICP) recorded from the penis in adult, male Sprague-Dawley rats anesthetized
      with chloral hydrate was employed as our experimental index for penile erection.
      Microinjection bilaterally of a NO-independent sGC activator, YC-1 (0.1 or 1
      nmol) or a cGMP analog, 8-Bromo-cGMP (0.1 or 1 nmol), into the HF elicited a
      significant reduction in baseline ICP. Bilateral application into the HF of
      equimolar doses (0.5 or 1 nmol) of a sGC inhibitor, LY83583 or a NO-sensitive sGC
      inhibitor, ODQ significantly antagonized the decrease in baseline ICP induced by
      co-administration of the NO precursor, L-arginine (5 nmol), along with
      significant enhancement of the magnitude of papaverine-induced elevation in ICP.
      In contrast, a peroxynitrite scavenger, L-cysteine (50 or 100 pmol), or an active
      peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis-(N-methyl-4'-pyridyl)
      porphyrinato iron (III) (10 or 50 pmol), was ineffective in both events. These
      results suggest that NO may participate in negative feedback regulation of penile
      erection by activating the sGC/cGMP cascade in the HF selectively.

PMID- 14654148
TI  - Parametric analysis of carotid plaque using a clinical ultrasound imaging system.
AB  - We evaluated quantitative ultrasonic methods for assessment of carotid plaque
      content. In vitro measurements of fixed, carotid plaque specimens obtained by
      surgical endarterectomy were performed using a clinical Philips HDI 5000 imaging
      system connected to a radiofrequency (RF) signal-acquisition system. We acquired
      RF signals and grey-scale images from carotid specimens (n = 17) and a tissue
      mimicking reference phantom. Imaged plaque sections were then classified
      according to histology. Parametric images were constructed from the integrated
      backscatter (IBS), and the midband, slope and intercept values of a straight-line
      fit to the apparent backscatter transfer function. Analysis was performed on 82
      regions-of-interest (ROIs). The IBS values for collagen, lipid and hemorrhage
      plaques were 5.8 +/- 5.4, 3.9 +/- 3.7, 2.8 +/- 2.2 dB, respectively. Midband and
      IBS parameter images exhibited good agreement in morphology with histology,
      whereas the slope and intercept parameter images were noisy. Mean IBS, midband,
      and grey-scale values of complex plaques were found to be statistically different
      (p < 0.05) from lipid, hemorrhage and fibrolipid plaques. The bias and limits of
      agreement (1.3 +/- 4.9 dB) between the grey-scale and IBS methods, however,
      indicated that the two methods were not interchangeable. Results indicate
      necessary improvements, such as reduction of large measurement variances and
      identification of robust parameters, that will permit multiparametric
      characterization of carotid plaque under in vivo conditions.

PMID- 14654105
TI  - Identification and characterisation of SB-366791, a potent and selective
      vanilloid receptor (VR1/TRPV1) antagonist.
AB  - Vanilloid receptor-1 (TRPV1) is a non-selective cation channel, predominantly
      expressed by peripheral sensory neurones, which is known to play a key role in
      the detection of noxious painful stimuli, such as capsaicin, acid and heat. To
      date, a number of antagonists have been used to study the physiological role of
      TRPV1; however, antagonists such as capsazepine are somewhat compromised by non
      selective actions at other receptors and apparent modality-specific properties.
      SB-366791 is a novel, potent, and selective, cinnamide TRPV1 antagonist isolated
      via high-throughput screening of a large chemical library. In a FLIPR-based
      Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the
      response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis
      indicated a competitive mechanism of action with a pA2 of 7.71. In
      electrophysiological experiments, SB-366791 was demonstrated to be an effective
      antagonist of hTRPV1 when activated by different modalities, such as capsaicin,
      acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an
      effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of
      defining a useful tool compound, we also profiled SB-366791 in a wide range of
      selectivity assays. SB-366791 had a good selectivity profile exhibiting little or
      no effect in a panel of 47 binding assays (containing a wide range of G-protein
      coupled receptors and ion channels) and a number of electrophysiological assays
      including hippocampal synaptic transmission and action potential firing of locus
      coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791
      had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage
      gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB
      366791 is a new TRPV1 antagonist with high potency and an improved selectivity
      profile with respect to other commonly used TRPV1 antagonists. SB-366791 may
      therefore prove to be a useful tool to further study the biology of TRPV1.

PMID- 14654149
TI  - Image texture analysis of sonograms in chronic inflammations of thyroid gland.
AB  - The current practice in assessing sonographic findings of chronic inflamed
      thyroid tissue is mainly qualitative, based just on a physician's experience.
      This study shows that inflamed and healthy tissues can be differentiated by
      automatic texture analysis of B-mode sonographic images. Feature selection is the
      most important part of this procedure. We employed two selection schemes for
      finding recognition-optimal features: one based on compactness and separability
      and the other based on classification error. The full feature set included
      Muzzolini's spatial features and Haralick's co-occurrence features. These
      features were selected on a set of 2430 sonograms of 81 subjects, and the
      classifier performance was evaluated on a test set of 540 sonograms of 18
      independent subjects. A classification success rate of 100% was achieved with as
      few as one optimal feature among the 129 texture characteristics tested. Both
      selection schemes agreed on the best features. The results were confirmed on the
      independent test set. The stability of the results with respect to sonograph
      setting, thyroid gland segmentation and scanning direction was tested.

PMID- 14654150
TI  - The usefulness of quantitative ultrasound at the hand phalanges in the detection
      of the different types of nontraumatic fractures.
AB  - The aim of this retrospective study was to determine whether quantitative
      ultrasound (QUS) at the hand phalanges has the ability to discriminate between
      individuals without and with different types of nontraumatic fractures. All women
      (n = 2466) (age range 38-88 years) not affected by metabolic diseases or under
      treatment with drugs known to interfere with bone metabolism were divided into
      controls without fractures (n = 1883) and women with nontraumatic previous
      fractures (n = 583). Fractures were the result of minimal trauma involving a fall
      from a standing height or less during normal daily activity. Fractured group was
      divided into subgroups on the basis of the types of fractures: hip, spine, wrist
      or other fractures. Skeletal status was assessed using the DBM Sonic 1200 (IGEA,
      Carpi, Italy) which measures the amplitude-dependent speed of sound, Ad-SoS (m/s)
      in the distal metaphyses of the proximal phalanges of the second through fifth
      finger of the dominant hand. Women with hip, spine, wrist or other fractures had
      significantly lower Ad-SoS values than controls (1814 +/- 60 m/s, 1829 +/- 57
      m/s, 1870 +/- 64 m/s, 1893 +/- 66 m/s, respectively, vs. 1943 +/- 73 m/s, p <
      0.001). Ad-SoS revealed the following areas under the ROC curve: 0.91 +/- 0.027
      for hip fracture, 0.89 +/- 0.019 for spine fracture, 0.77 +/- 0.012 for wrist
      fracture and 0.70 +/- 0.023 for other fractures. By multiple logistic regression
      analysis, the probability of having fracture, estimated as odds ratio for each 1
      SD reduction in Ad-SoS, was: 3.49 (95% CI, 1.57-7.75) for hip, 3.25 (95% CI, 1.94
      5.45) for spine, 2.24 (95% CI, 1.86-2.70) for wrist and 1.81 (95% CI, 1.36-2.40)
      for other fractures. The present study demonstrates the ability of phalangeal QUS
      to discriminate between subjects with and without different types of nontraumatic
      fractures. Phalangeal QUS revealed the best sensitivity and specificity in
      discriminating hip- and spine-fractured patients from controls.

PMID- 14654151
TI  - Estimation of fractional moving blood volume in fetal lung using Power Doppler
      ultrasound, methodological aspects.
AB  - Perfusion estimation of the fetal lung is an important predictor of its maturity
      and function after birth. Ultrasound (US) power Doppler has previously been used
      to assess the perfusion of the fetal lung, based on the mean pixel intensity
      (MPI) over a region-of-interest (ROI). The drawback is that the MPI is not only
      dependent on the amount of flowing blood, but also depth, gain and attenuation in
      overlying tissue layers. In this study, power Doppler images have been analysed
      according to a previously published method that attempts to compensate for such
      unwanted variations, resulting in a measure termed fractional moving blood volume
      (FMBV). A total of 29 singleton pregnancies with normally grown fetuses were
      evaluated after 35 weeks of gestation. For reliable interpatient comparisons, we
      found it always necessary to use a well-defined section of the fetal lung.
      Therefore, all scans were performed in a transverse plane of the fetal thorax
      with a four-chamber view of the heart, through the intercostal space. ROIs in 12
      left and 17 right fetal lungs were defined (the fetal lung closest to the
      transducer was always examined). No differences in estimated FMBV or MPI were
      found between left and right lungs. Similarly, there was no significant
      difference between images acquired during systole and diastole. FMBV is
      compensated for depth and, also, for other sources of power variation, as
      reflected in the coefficient of variation: 0.14 for FMBV and 0.24 for MPI. A scan
      on a test phantom reveals that the power in dB is linearly related to velocity
      over a limited range, suggesting that FMBV might be useful for discriminating
      between normal and decreased fetal lung perfusion.

PMID- 14654152
TI  - An automatic approach for morphological analysis and malignancy evaluation of
      ovarian masses using B-scans.
AB  - Ovarian masses are a common phenomenon among women of all ages. The importance of
      prompt diagnosis of ovarian malignancies is obvious, due to the high mortality
      rate and the difficulty to detect a tumor in its early stages. In this work, an
      automatic technique for quantitative analysis and malignancy detection of ovarian
      masses using B-scan ultrasound (US) images is presented. The core of the
      technique is morphologic analysis of the ovarian mass. The method employed for
      this task is divided into two major stages: initial classification of the mass
      (into one of the three major tumor types: cyst, semisolid, solid), and detailed
      analysis of the mass. Malignancy evaluation is performed based on the collected
      data and the criteria provided by commonly used scoring systems. The results
      reflect adequate performance of the automatic method developed (referring to
      clinical requirements).

PMID- 14654153
TI  - Segmentation of breast tumor in three-dimensional ultrasound images using three
      dimensional discrete active contour model.
AB  - In this paper, we apply the three-dimensional (3-D) active contour model to a 3-D
      ultrasonic data file for segmenting of the breast tumor. The 3-D ultrasonic file
      is composed of a series of two-dimensional (2-D) images. Most of traditional
      techniques of 2-D image segmentation will not use the information between
      adjacent images. To suit the property of the 3-D data, we introduce the concept
      of the 3-D stick, the 3-D morphologic process and the 3-D active contour model.
      The 3-D stick can get over the problem that the ultrasonic image is full of
      speckle noise and highlight the edge information in images. The 3-D morphologic
      process helps to determine the contour of the tumor and the resulting contour can
      be regarded as the initial contour of the active contour model. Finally, the 3-D
      active contour model will make the initial contour approach to the real contour
      of the tumor. However, there is emphasis on these 3-D techniques that they do not
      consist of a series of 2-D techniques. When they work, they will consider the
      horizontal, vertical and depth directions at the same time. The use of these 3-D
      techniques not only segments the 3-D shape but also obtains the volume of the
      tumor. The volume of the tumor calculated by the proposed method will be compared
      with the volume calculated by the VOCAL software with the physician's manually
      drawn shape and it shows that the performance of our method is satisfactory.

PMID- 14654154
TI  - BSS-based filtering of physiological and ARFI-induced tissue and blood motion.
AB  - Blind source separation (BSS) for adaptive filtering is presented in application
      to imaging both physiological and acoustic radiation force impulse (ARFI)-induced
      tissue and blood motion in the common carotid artery. The collected raw
      radiofrequency (RF) data includes vessel wall motion, blood flow and ARFI-induced
      motion. In the context of these complex motion patterns, the same BSS adaptive
      filtering method was employed for three diverse applications: 1. clutter
      filtering ensembles prior to blood velocity estimation, 2. extracting small axial
      velocity components from noisy velocity measurements given large flow angles and
      3. reducing noise in measured ARFI-induced tissue displacement profiles to
      enhance differentiation of local tissue structures. The filter separated
      physiological vessel wall motion from axial blood flow and ARFI-induced motion;
      successful filter performance is demonstrated in velocity estimates, color flow
      images and ARFI displacement profiles. The results demonstrate the breadth of
      applications for BSS adaptive filtering in the clinical imaging environment.

PMID- 14654155
TI  - Radiation-force technique to monitor lesions during ultrasonic therapy.
AB  - This report describes a monitoring technique for high-intensity focused
      ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs)
      and those made for noninvasive cardiac therapy and tumor treatment in the eye,
      liver and other organs. Designed to sense the increased stiffness of a HIFU
      lesion, this technique uniquely utilizes the radiation force of the therapeutic
      US beam as an elastographic push to detect relative stiffness changes.
      Feasibility was demonstrated with computer simulations (treating acoustically
      induced displacements, concomitant heating, and US displacement-estimation
      algorithms) and pilot in vitro experimental studies, which agree qualitatively in
      differentiating HIFU lesions from normal tissue. Detectable motion can be induced
      by a single 5 ms push with temperatures well below those needed to form a lesion.
      Conversely, because the characteristic heat diffusion time is much longer than
      the characteristic relaxation time following a push, properly timed multiple
      therapy pulses will form lesions while providing precise control during therapy.

PMID- 14654156
TI  - Probe calibration for freehand 3-D ultrasound.
AB  - Ultrasound (US) probe calibration establishes the rigid body transformation
      between the US image and a tracking device attached to the probe. This is an
      important requirement for correct 3-D reconstruction of freehand US images and,
      thus, for accurate surgical navigation based on US. In this study, we evaluated
      three methods for probe calibration, based on a single-point phantom, a wire
      cross phantom requiring 2-D alignment and a wire phantom for freehand scanning.
      The processing of acquired data is fairly common to these methods and, to a great
      extent, based on automated procedures. The evaluation is based on quality
      measures in 2-D and 3-D reconstructed data. With each of the three methods, we
      calibrated a linear-array probe, a phased-array sector probe and an
      intraoperative probe. The freehand method performed best, with a 3-D navigation
      accuracy of 0.6 mm for one of the probes. This indicates that clinical accuracy
      in the order of 1 mm may be achieved in US-based surgical navigation.

PMID- 14654157
TI  - Threshold estimates and superthreshold behavior of ultrasound-induced lung
      hemorrhage in adult rats: role of pulse duration.
AB  - The study objective was to estimate the pressure threshold (ED(05), effective
      dose, or in situ peak rarefactional pressure associated with 5% probability of
      lesions) of ultrasound (US)-induced lung hemorrhage as a function of pulse
      duration (PD) in adult rats. A total of 220 10- to 11-week-old 250-g female
      Sprague-Dawley rats (Harlan) were randomly divided into 20 ultrasonic exposure
      groups (10 rats/group) and one sham group (20 rats). The 20 ultrasonic exposure
      groups (2.8-MHz; 10-s exposure duration; 1-kHz PRF; -6-dB pulse-echo focal beam
      width of 470 microm) were divided into four PD groups (1.3, 4.4, 8.2 and 11.6
      micros) and, for each PD group, there were five in situ peak rarefactional
      pressures (range between 4 and 9 MPa). Rats were weighed, anesthetized,
      depilated, exposed, and euthanized under anesthesia. The left lung was removed
      and scored for the occurrence of hemorrhage. If hemorrhage was present, the
      lesion surface area and depth were measured. Individuals involved in animal
      handling, exposure and lesion scoring were "blinded" to the exposure conditions.
      Logistic regression analysis was used to examine the dependence of the lesion
      occurrences, and Gaussian tobit regression analysis was used to examine the
      dependence of the lesion surface areas and depths on in situ peak rarefactional
      pressure and PD. Threshold results are reported in terms of ED(05). For PDs of
      1.3, 4.4, 8.2 and 11.6 micros, respectively, lesion occurrence ED(05)s were 3.1,
      2.8, 2.3 and 2.0 MPa with standard errors around 0.6 MPa. Lesion size ED(05)s
      showed similar values. A mechanical index (MI) of 1.9, the US Food and Drug
      Administration (FDA) regulatory limit of diagnostic US equipment, is equivalent
      to the adult rat's in situ peak rarefactional pressure of 4.0 MPa. PDs of 8.2 and
      11.6 micros had ED(05)s more than 2 standard errors below 4.0 MPa, indicating
      that the ED(05)s of these two PDs are statistically significantly different from
      4.0 MPa. The ED(05) threshold levels for a PD of 1.3 micros are consistent with
      previous US-induced lung hemorrhage studies. As the PD increases, the ED(05)
      levels decrease, suggesting greater likelihood of lung damage as the PD
      increases. All of the ED(05)s are less than the FDA limit.

PMID- 14654158
TI  - Enhancement of antitumor effects of 5-fluorouracil combined with ultrasound on
      Ehrlich ascites tumor in vivo.
AB  - To evaluate the role of ultrasonic waves in enhancing the effect of 5
      fluorouracil (5-FU) as anticancer drug, tumor growth, cell ultrastructure and
      temperature rises of ascites Ehrlich tumor implanted in mice were investigated at
      a frequency of 0.8 MHz. Different conditions of ultrasonic intensity (1, 2 and 3
      W/cm(2)), sonocation time (1, 3 and 5 min) and waveform (continuous and pulsed)
      were studied. A total of 10 mg/kg body weight of 5-FU was IV injected into the
      mice bearing Ehrlich tumors on days of 1, 3, 5, 8, 10 and 12 of therapy. After 24
      h of each injection with 5-FU, tumor sites were sonocated at room temperature of
      22 degrees C. Tumor volumes were monitored by using ultrasonic imaging system
      during treatment just before each 5-FU injection, and on the 15th day of
      treatment. Density and ultrasonic attenuation of excised tumor tissues were
      measured in vitro and used to estimate the temperature rises due to ultrasonic
      absorption. Density and attenuation coefficients of excised tumor tissues were
      found to be dependent on the treatment regimen. The estimated rate of temperature
      rise and equilibrium temperature, and the characteristic time to reach
      equilibrium are given for each group. Results obtained indicate that tumor growth
      decreases with increasing of ultrasonic intensity and sonocation time. Tumor
      growth was delayed 4 to 6 days by combined treatment of 5- fluorouracil and
      ultrasound (US). Ultrastructure investigations of tumor cells showed severe
      damage in cytoplasmic organelles and cytoplasmic vacuoles that increased with
      increasing ultrasonic intensity and sonocation time. This damage appears as
      prominent crowded vacuoles among swollen ruptured organelles, chromatin fragments
      and severe increase in numbers of pyknotic and apoptotic cells.

PMID- 14654159
TI  - The effects of pulsed low-intensity ultrasound on chondrocyte viability,
      proliferation, gene expression and matrix production.
AB  - This study was designed to examine the effects of pulsed low-intensity ultrasound
      (PLIUS) on chondrocyte viability, proliferation, matrix production and gene
      expression. Chondrocytes were isolated from the distal part of the sternum of 16
      day-old chick embryos and cultured in alginate beads. PLIUS at 2 mW/cm(2) (group
      PLIUS(2)) and 30 mW/cm(2) (group PLIUS(30)) was applied to chondrocytes for a
      single 20-min treatment. A control group was treated without PLIUS. The viability
      of chondrocytes was not affected by exposure to PLIUS. PLIUS influenced
      chondrocyte proliferation in an intensity-dependent manner. By day 7 after
      application of PLIUS, the gene expression and synthesis of aggrecan was the same
      as in the controls. At this same time point, the expression and synthesis of type
      II collagen was not different between the controls and PLIUS(30), but was
      increased in PLIUS(2). PLIUS was shown to inhibit the expression of type X
      collagen. This inhibition of chondrocyte hypertrophy may prove to be significant
      in the management of cartilage degeneration.

PMID- 14654160
TI  - An extended commentary on "Models and regulatory considerations for transient
      temperature rise during diagnostic ultrasound pulses" by Herman and Harris
      (2002).
AB  - This commentary addresses the matter of misinterpretation of thermal dose as
      discussed by Herman and Harris (2002), and shows that the thermal doses they
      would consider as ineffective (i.e., "safe") for producing a hyperthermia-induced
      teratologic effect, can be highly effective ones. The matter of whether or not
      thermal thresholds exist for teratologic effects is reviewed. There are only
      opinions about thresholds. The critical experiments for ascertaining whether or
      not a threshold exists have not been undertaken. A power computation illustrates
      the requisite sample sizes (litters, fetuses) for undertaking an experimental
      test of whether the hyperthermic teratologic response in rats is characterized by
      threshold or simple linearity kinetics.

PMID- 14654162
TI  - The lymphocytic cholinergic system and its contribution to the regulation of
      immune activity.
AB  - Lymphocytes express most of the cholinergic components found in the nervous
      system, including acetylcholine (ACh), choline acetyltransferase (ChAT), high
      affinity choline transporter, muscarinic and nicotinic ACh receptors (mAChRs and
      nAChRs, respectively), and acetylcholinesterase. Stimulation of T and B cells
      with ACh or another mAChR agonist elicits intracellular Ca2+ signaling, up
      regulation of c-fos expression, increased nitric oxide synthesis and IL-2-induced
      signal transduction, probably via M3 and M5 mAChR-mediated pathways. Acute
      stimulation of nAChRs with ACh or nicotine causes rapid and transient Ca2+
      signaling in T and B cells, probably via alpha7 nAChR subunit-mediated pathways.
      Chronic nicotine stimulation, by contrast, down-regulates nAChR expression and
      suppresses T cell activity. Activation of T cells with phytohemagglutinin or
      antibodies against cell surface molecules enhances lymphocytic cholinergic
      transmission by activating expression of ChAT and M5 mAChR, which is suggestive
      of local cholinergic regulation of immune system activity. This idea is supported
      by the facts that lymphocytic cholinergic activity reflects well the changes in
      immune system function seen in animal models of immune deficiency and immune
      acceleration. Collectively, these data provide a compelling picture in which
      lymphocytes constitute a cholinergic system that is independent of cholinergic
      nerves, and which is involved in the regulation of immune function.

PMID- 14654163
TI  - Metabolism and potency of xenin and of its reduced hexapseudopeptide psi fragment
      in the dog.
AB  - Xenin is a 25 amino acid peptide hormone, secreted into the circulation by
      specific endocrine cells in the duodenal mucosa. Plasma concentrations are
      elevated after sham feeding and feeding. In the present study the metabolism of
      xenin and of a C-terminal fragment was investigated. Xenin, its C-terminal
      hexapeptide, and a pseudopeptide analog psi (CH2NH) hexapeptide in which a psi
      reduced bond is introduced in the biologically important dibasic motif of the C
      terminus were infused or injected intravenously in 14 anaesthetized dogs. Plasma
      disappearance time, metabolic clearance rate, the generation of metabolites, and
      biological effects on exocrine pancreatic secretion were determined employing
      radioimmunoassay, high pressure liquid chromatography, mass spectrometry (MALDI
      MS), and sequence analysis. Half time after steady state infusion of xenin was
      3.1 min(-1), that of psi xenin 6 was 6.2(-1) (p<0.01) Plasma concentrations of
      psi xenin 6 were significantly elevated (p<0.01), pancreatic secretion of volume
      was augmented by a factor of 50, and output of protein by a factor of 30 compared
      to unmodified xenin 6. MALDI-MS and sequencing after infusion of xenin revealed a
      C-terminal octapeptide fragment as primary metabolite. Introduction of a reduced
      pseudobond in the dibasic motif of xenin dramatically enhances biological
      potency. This indicates that such a reduced pseudopeptide may be useful in the
      treatment of bowel paralysis.

PMID- 14654164
TI  - Inhibitory effect of quercetin on carrageenan-induced inflammation in rats.
AB  - We examined the effect of quercetin on the inflammatory response induced by
      carrageenan in the rat. Air pouches were induced subcutaneously on the backs of
      rats and injected with carrageenan. The rats were treated with either vehicle or
      quercetin at a dose of 10 mg/kg one hour before carrageenan challenge. Fourty
      eight hour after carrageenan challenge, the air pouches were removed and
      analyzed. The volume, protein amounts and cell counts in the exudation obtained
      from the quercetin-treated animals were significantly reduced compared to those
      from vehicle-treated animals. The contents of PGE(2), TNF-alpha, RANTES, MIP-2
      and the mRNA for cyclooxygenase-2 were also suppressed in these rats. The
      histological examination displayed the suppression of the inflammatory response
      in the pouch tissues from quercetin-treated rats. As the anti-inflammatory effect
      of the flavonols was more or less at the similar level among the quercetin-,
      isoquercitrin- or rutin-treated rats, it appeared that the sugar parts did not
      influence on the anti-inflammatory effect. Our study indicated that the flavonols
      modulated the inflammatory response, at least in part, by modulating the
      prostanoid synthesis as well as cytokine production.

PMID- 14654165
TI  - Vasodilation by banhabackchulchunmatang, a Chinese medicine, is associated with
      negative modulation of PKCalpha activation and NO production.
AB  - Banhabackchulchunmatang (BCT) is a widely used herbal medicine with vasodilatory
      actions. In the present study, we investigated the subcellular mechanisms of its
      vascular actions. Both in the presence and absence of endothelium, BCT relaxed
      vascular strips precontracted with phenylephrine, but the magnitude of relaxation
      was greater in the presence of endothelium. The relaxation was inhibited by
      either L-NAME, an NOS inhibitor, or methylene blue, a cGMP inhibitor, indicating
      the involvement of nitric oxide (NO). The involvement of NO was supported by the
      increased formation of nitrite from human umbilical vein endothelial cells in the
      presence of BCT. In vascular strips, BCT lowered the phosphorylation level of the
      20 kDa myosin light chains. BCT also directly inhibited phenylephrine-induced
      protein kinase Calpha (PKCalpha) translocation in freshly isolated single ferret
      portal vein smooth muscle cells. Together, these effects are likely to contribute
      to the vasodilatory actions of BCT.

PMID- 14654166
TI  - Genistein administration decreases serum corticosterone and testosterone levels
      in rats.
AB  - The phytochemical flavonoid genistein has been shown to act as a potent
      competitive inhibitor of human adrenocortical 3beta-hydroxysteroid dehydrogenase
      and cytochrome P450 21-hydroxylase activities in vitro [J. Steroid Biochem.
      Molec. Biol. 2002; 80: 355-363]. In the present study, we evaluated the effects
      of large amounts of genistein continuously administered to weanling rats,
      particularly on steroidogenesis at the pubertal stage in vivo. Serum
      concentrations of free and total genistein were significantly higher in the 40
      mg/kg genistein administration group when compared with the control group. In
      genistein administered rats, adrenal weight was significantly higher.
      Furthermore, a clear expansion of cells was observed in hematoxylin and eosin
      stained tissue at the zona fasciculata and zona reticularis of the adrenal
      cortex. However in the testis, no differences in weights or histologic changes
      were observed. Serum corticosterone concentration significantly decreased to 50%
      of control levels by 40 mg/kg genistein administration and testosterone also
      tended to decrease with this dose of genistein. On the other hand, although serum
      follicle stimulating hormone was unchanged, adrenocorticotropic hormone and
      luteinizing hormone levels increased with genistein administration. These results
      suggest a significant effect of genistein on steroidogenesis in the adrenal gland
      and testis of rats, and this effect appeared to be more evident on steroid
      production in adrenals than in testis in vivo.

PMID- 14654168
TI  - Switching off HSP70 and i-NOS to study their role in normal and H2O2-stressed
      human fibroblasts.
AB  - i-NOS and HSP70 antisense oligonucleotides were used to study the role of the two
      well known stress-regulated molecules on cell survival of both untreated control,
      and H2O2-stressed human fibroblasts. Cell survival was assessed either by LDH
      release or by MTT assay. The levels of cytosolic i-NOS and HSP70 were tested by
      using immunoblotting analysis, and reactive oxygen species (ROS) production was
      quantified. Compared to the values observed in untreated control cells, anti
      HSP70-transfected human fibroblasts showed an increase in ROS production, i-NOS
      level and LDH release. The addition of 0.12 mM H2O2 for 20 min. to the HSP70
      deprived fibroblasts did not modify the percentage of LDH release observed in
      H2O2 stressed cells, but reduced cell viability increasing both ROS production
      and i-NOS level. Anti i-NOS-transfected fibroblasts, compared to the control
      untreated cells, showed no modification in ROS production, while cell survival
      was improved. When treated with H2O2 the i-NOS depleted cells counteracted ROS
      formation as well as LDH release but negatively affected cell viability and HSP70
      levels, compared to the results obtained with H2O2 alone-treated fibroblasts. The
      data indicates that the induced decrease in HSP70 level in oxidative stress
      conditions makes fibroblasts more prone to oxidative injury and also increases i
      NOS level. Whereas in one way the forced decrease in i-NOS expression seems to
      counteract ROS production stimulated by the oxidative insult in the cells, in
      another way, since it causes a decrease in HSP70 expression as well as in cell
      viability, it seems to activate some unidentified pathways affecting cell demise.

PMID- 14654167
TI  - Morin sulfates/glucuronides exert anti-inflammatory activity on activated
      macrophages and decreased the incidence of septic shock.
AB  - Morin is a flavonoid present in fruits and Chinese herbs. Based on in vitro
      studies, morin has been reported to show various beneficial biological
      activities. However, there is growing evidence that conjugative metabolism is
      central to the biological fate of flavonoids. Therefore, the biological effects
      of morin could be primarily determined by its conjugated metabolites. In this
      study, the effects of morin and its sulfates/glucuronides on the production of
      nitric oxide (NO) and cytokines from lipopolysaccharide (LPS)-activated
      macrophages were individually investigated and compared. The results indicated
      that the 50% NO production was inhibited from LPS-activated RAW 264.7 cells by
      1.25 mM morin and 1.25 microM morin sulfates/glucuronides. Meanwhile, the 50%
      inhibition concentration (IC50) values of morin and morin sulfates/glucuronides
      in activated peritoneal macrophages were 1.5 mM morin and 1.5 microM morin
      sulfates/glucuronides, respectively. In addition, 30% of the tumor necrosis
      factor-alpha (TNF-alpha) and 35% of the interleukin (IL)-12 productions from
      activated macrophages were inhibited by 2-2.5 mM morin and 2-2.5 microM morin
      sulfates/glucuronides, respectively. Furthermore, phagocyte activities in the
      peripheral blood of those for mice dosed with morin for two months were about 65
      70% of controls. Lower NO production and reduced macrophage phagocytic activities
      corresponded to LPS-resistant state. These findings indicated that morin may
      exhibit anti-inflammatory activity and reduced the incidence of experimental
      septic shock through decreasing the functions of macrophages and may regulate
      immune response through modulating the cytokine profiles. Therefore, morin could
      be a promising therapeutic candidate for inflammatory disease due to the strong
      activity of its metabolites.

PMID- 14654169
TI  - The protective effect of ascorbic acid derivative on PC12 cells: involvement of
      its ROS scavenging ability.
AB  - L-ascorbic acid 2-phosphate-6-palmitate (Asc2P6P) was synthesized and its effect
      on the damage of PC12 cells induced by H2O2 was investigated. 200 microM H2O2 in
      a treatment period of 4 hours in our experiment resulted in substantial cell
      loss. With the increasing concentration of antioxidants, such H2O2-induced
      cytotoxicity was significantly prevented and the corresponding intracellular and
      extracellular ROS levels decreased concurrently by pre-treatment with Asc2P6P and
      Asc. It was found that Asc2P6P was superior to L-ascorbic acid in its protective
      role and showed a dose-dependent manner during a 24-hour treatment. The higher
      potency of Asc2P6P's protective role on PC12 cells was correlated with its more
      effective ROS scavenging ability. HPLC assay demonstrated that Asc2P6P could
      easily enter the cells and be converted into Asc persistently, which contributed
      to its distinguished role in protecting PC12 cells against H2O2-induced
      cytotoxicity.

PMID- 14654170
TI  - Pretreatment with PKC inhibitor triggers TNF-alpha induced apoptosis in TNF-alpha
      resistant B16 melanoma BL6 cells.
AB  - Tumor necrosis factor alpha (TNF-alpha) modulates various events through several
      different pathways. Many tumor cells are resistant to this cytokine. Pretreatment
      of these cells with actinomycin D enhances TNF-alpha-induced apoptosis. In the
      present study, we investigated the mechanism of this enhancement and whether or
      not the apoptosis of TNF-alpha-resistant cancer cells can be induced by the
      inhibition of Protein kinase C (PKC). When TNF-alpha was added after inhibition
      of PKC by H7, apoptosis was observed, and companied with the activation of
      nuclear factor kappa B (NF-kappaB). After the inhibition of protein kinase B
      (Akt) by LY294002 or p38 mitogen-activated protein kinase (p38MAPK) by SB203580,
      the addition of TNF-alpha did not cause apoptosis. However, after the inhibition
      of MAPK/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) with U0126,
      apoptosis was observed when TNF-alpha was added. In the Western blotting
      analysis, phosphorylation of MEK1/2 occurred at 60 minutes after the addition of
      TNF-alpha. However, it was noted that after pretreatment with H7, a significant
      decrease in phosphorylated MEK1/2 was observed. The present findings suggest that
      MEK1/2 plays an important role in TNF-alpha-resistance in TNF-alpha-resistant B16
      melanoma BL6 cells. Furthermore, it was found that MEK1/2 is more important than
      NF-kappaB, Akt, and p38MAPK in anti-apoptotic PKC signaling and that TNF-alpha
      resistance can be overcome by inhibiting MEK1/2. These results suggest the
      possibility of development of a new anticancer drug treatment.

PMID- 14654171
TI  - Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced
      hepatotoxicity in the rat.
AB  - Overproduction of nitric oxide (NO) in the liver has been implicated as an
      important event in endotoxin shock and in other models of hepatic inflammation
      and injury. The present study was undertaken to evaluate the effect of ONO-1714,
      a potent and specific inhibitor of inducible NO synthase (iNOS), on acetaminophen
      induced hepatotoxicity in the rats. Oral administration of ONO-1714 dose
      dependently inhibited NOx (NO2- and NO3-) accumulation in rat plasma after
      lipopolysaccharide (LPS) treatment. Intraperitoneal acetaminophen at 1 g/kg
      caused damage to the centrilobular regions of the liver and increase in serum
      alanine and aspartate transaminase (ALT and AST, respectively) levels accompanied
      by elevated plasma NOx levels after 24 h. Oral administration of ONO-1714 at 10
      and 100 microg/kg dose-dependently reduced the acetaminophen-induced hepatic
      tissue damage and the increases in serum ALT and AST levels. ONO-1714 also
      blocked the increase in plasma NOx concentrations. These findings demonstrate
      that oral ONO-1714, an iNOS inhibitor, protects against acetaminophen-evoked
      hepatic inflammation/injury, strongly suggesting that NO produced by iNOS plays a
      key role in the pathogenesis of this drug-induced hepatotoxicity.

PMID- 14654172
TI  - Influence of acute resistance exercise on cardiac biomarkers in untrained women.
AB  - This study was conducted to determine if an initial bout of resistance (weight
      lifting) exercise by untrained women results in any alterations in indicators of
      acute myocardial infarction (AMI). Untrained women performed 4 resistance
      exercises at 70% of their 1 repetition maximum. Blood samples were obtained
      during the 12 h post-exercise and analyzed for total creatine kinase (CK)-MB, CK
      MB subforms 1 and 2, and the relative lymphocyte percentage. Exercise resulted in
      significant increases in total CK-MB, CK-MB(1), CK-MB(2), and the CK-MB(2)/CK
      MB(1) ratio, total leukocyte count, and lymphocyte count. Using several criteria
      for the assessment of AMI, 22-25% of subjects completing the protocol
      demonstrated increases in CK-MB(2), CK-MB(2)/CK-MB(1) ratio, and relative
      lymphocyte percentages that were suggestive of AMI. Thus, our data suggest that
      moderate resistance exercise can significantly alter blood indicators of AMI,
      emphasizing the need to determine recent exercise history in patients with
      possible AMI.

PMID- 14654173
TI  - Short-term risk after initial observation for chest pain.
AB  - Few studies have evaluated the necessity of immediate stress testing after
      observation for chest pain. The purpose of this study was to assess the safety of
      outpatient stress testing after discharge from a chest pain unit. We hypothesized
      that discharge from a chest pain unit before stress testing is associated with a
      low rate of short-term adverse outcomes. This was a retrospective chart review of
      managed care patients discharged from the chest pain unit before the performance
      of stress testing. Records were reviewed for the occurrence of adverse cardiac
      outcomes before an outpatient stress test up to 60 days post-discharge. Primary
      outcomes were defined as death or myocardial infarction, and secondary outcomes
      as readmission for chest pain evaluation, unstable angina, or congestive heart
      failure. Three hundred forty-four patients were identified. One hundred sixty-six
      patients had either a recent prior stress test (17) or an outpatient test (149)
      performed within 60 days of discharge. During that time, 2 patients (0.6%) had a
      fatal out-of-hospital cardiac event, and there were 27 subsequent chest pain
      visits to the Emergency Department by 24 patients (7.0%). Nine patients (2.6%)
      were admitted to the hospital and 10 (2.9%) were readmitted to the observation
      unit for chest pain. We conclude that patients who have negative serial
      electrocardiograms and enzyme testing in a chest pain unit are at low risk for
      short-term cardiac events. Appropriately selected patients may be discharged for
      subsequent outpatient testing.

PMID- 14654174
TI  - Use of diagnostic testing in the emergency department for patients presenting
      with non-traumatic abdominal pain.
AB  - The objective of the study was to measure the utilization and diagnostic value of
      tests used in the Emergency Department (ED) on patients with undifferentiated non
      traumatic abdominal or flank pain. Specific goals were to measure how often these
      tests led to changes in diagnosis or disposition, which tests were most commonly
      used, and which tests providers considered most helpful. We conducted a pilot
      single-center, prospective descriptive study, enrolling all eligible adult
      patients who presented to our ED with non-traumatic abdominal or flank pain
      during defined hours of our intake period. Based on serial provider interviews
      pre- and post-testing, we measured the frequency of change of most likely
      diagnosis and disposition, which tests were performed, and the provider-perceived
      value of tests. We enrolled 124 subjects with a mean age of 44 years; 27% were
      admitted. Testing led to a change in most likely diagnosis in 37% of subjects,
      and in disposition in 41%. Frequency of diagnostic test use varied from a high of
      93% for CBC to 6% for a blood or urine culture. Overall, 65% of patients had at
      least one imaging study performed, and 39% had an abdominal/pelvic computed
      tomography (CT) scan. Over all subjects, providers identified the most useful
      tests as the CT scan (31%) and urinalysis (17%). In conclusion, among ED patients
      who presented with non-traumatic abdominal or flank pain to one academic center,
      the pre-test most likely diagnosis and disposition were changed based on the ED
      evaluation in over one-third of subjects. Almost all received blood tests and two
      thirds received one or more imaging studies. Based on providers' subjective
      opinions, the most valuable tests were the abdomino/pelvic CT scan and the
      urinalysis.

PMID- 14654175
TI  - Sonographic intraperitoneal fluid in patients with pelvic fracture: two cases of
      traumatic intraperitoneal bladder rupture.
AB  - Two patients who presented to the Emergency Department (ED) in shock with severe
      pelvic fractures were evaluated for intra-abdominal injury with a focused
      assessment with sonography in trauma (FAST) examination. Free intraperitoneal
      fluid was identified in the hepato-renal recess of both patients. At laparotomy
      both patients were found to have extensive uroperitoneum resulting from
      intraperitoneal bladder rupture and no other intra-abdominal injuries. The source
      of shock in both cases was ultimately determined to be arterial hemorrhage from
      pelvic vessels. The utility of FAST examinations in the setting of major pelvic
      injury is relatively unstudied. Coincident injuries make the evaluation for
      source of hemorrhage in this subset of patients challenging. This is a report of
      sonographic intraperitoneal fluid in the setting of major pelvic injury and
      hemodynamic instability found to be uroperitoneum and not hemoperitoneum.

PMID- 14654176
TI  - Intermediate syndrome after exposure to chlorpyrifos in a 16-month-old girl.
AB  - We describe a case of intermediate syndrome after chlorpyrifos ingestion in a
      toddler, despite a continuous pralidoxime infusion. A 16-month-old girl ingested
      a pesticide containing chlorpyrifos. She was brought to an Emergency Department
      where she became lethargic and tachycardic, and subsequently developed pulmonary
      edema requiring mechanical ventilation. Pralidoxime 150 mg i.v. was administered
      twice, and an infusion begun at 15 mg/kg/h. At 24.5 h post-ingestion the child
      had a normal neurologic examination, showed no signs of cholinergic excess, and
      was extubated successfully. At 27.5 h post-ingestion the child became flaccid,
      bradycardic and apneic. She was emergently re-intubated. The child's delayed
      onset of respiratory arrest and flaccid paralysis after an asymptomatic period is
      consistent with Intermediate Syndrome. This is an unusual case in that it
      occurred in a young child, was related to chlorpyrifos, and occurred despite
      continuous and adequate oxime therapy.

PMID- 14654177
TI  - PFAPA syndrome mimicking familial Mediterranean fever: report of a Turkish child.
AB  - The PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitidis) syndrome
      is characterized by periodic fever, adenitis, pharyngitis, and aphthous
      stomatitis. Herein, we present a Turkish child with PFAPA syndrome mimicking
      familial Mediterranean fever because of a rare presentation. A 9-year-old boy was
      admitted with recurrent fever, aphthous stomatitis, sore throat, headache, and
      general body pains, lasting 2 to 3 days since 3.5 years of age. He was completely
      symptom-free between the attacks. He was diagnosed as having familial
      Mediterranean fever according to the clinical findings when he was 6 years of age
      and Colchicum tablet was administrated. Despite colchicines therapy for 8 months,
      his attacks did not subside; therefore, the drug was discontinued. He had high
      fever, a painful cervical lymphadenopathy, aphthous stomatitis, and tonsillo
      pharyngitis. The patient was then diagnosed as having PFAPA syndrome. He was
      given a single dose of prednisolone (0.35 mg/kg/dose). His complaints
      dramatically and completely disappeared 3 h after administration of the drug.
      During the 8th month of follow-up, a similar febrile attack lasting only 1 day
      was noted and it was controlled with a single dose of prednisolone (0.5
      mg/kg/day). At this writing the patient is in the 12th month of follow-up, and
      there have been no symptoms after the second attack. In conclusion, our patient
      shows that PFAPA syndrome can be confused with familial Mediterranean fever. We
      also would like to emphasize that the typical PFAPA syndrome can be easily
      diagnosed by detailed history-taking and physical findings.

PMID- 14654178
TI  - Late postpartum eclampsia: a common presentation of an uncommon diagnosis.
AB  - We present two cases of late postpartum eclampsia. Both patients presented with a
      chief complaint of headache, and were diagnosed with eclampsia after the onset of
      seizures. Neither patient had proteinuria or edema. Further evaluation did not
      yield another diagnosis for the seizures, and treatment with i.v. magnesium
      sulfate was successful in stopping the seizures. No further seizure activity
      occurred in either patient.

PMID- 14654179
TI  - Acute airway compromise after brief exposure to a Dieffenbachia plant.
AB  - Dieffenbachia is a common domestic plant. Oral contact with the plant usually is
      associated with minimal consequences. However, chewing on the stem or the leaf of
      the Dieffenbachia can result in painful oropharyngeal edema and the inability to
      speak or handle secretions. Airway compromise has been reported only in a
      pediatric ingestion. We report a case of an adult who bit into the stem of the
      plant thinking it was sugar cane. He instantly spit out the remaining stem and
      despite this brief exposure, oropharyngeal edema developed refractory to
      medicinal therapy, requiring surgical airway management. The exact mechanism of
      edema is not known; therefore, methods of treatment are variable. We recommend
      caution when presented with a patient exposed to Dieffenbachia. Even the patient
      who initially seems stable may have an airway that will quickly deteriorate.

PMID- 14654180
TI  - Acute myocardial infarction as a complication of clonidine withdrawal.
AB  - Abrupt withdrawal from clonidine therapy is a well-known cause of hyperadrenergic
      symptoms, but reports of acute myocardial infarction are extremely rare. We
      present the case of an 86-year-old woman who developed severe hypertension and a
      myocardial infarction 36 h after terminating her therapy of clonidine, 0.4
      mg/day. Symptoms quickly responded to the administration of labetolol and
      diazepam. Subsequent cardiac catheterization showed no evidence of coronary
      occlusion, suggesting that excessive myocardial oxygen demand was responsible for
      the infarction.

PMID- 14654181
TI  - Complaints against an EMS system.
AB  - Complaints against Emergency Medical Services (EMS) agencies represent a
      concerning and potentially time-consuming problem for all involved in the
      delivery of prehospital emergency medical care. The objective of this study was
      to identify the source of complaints against an EMS system to help focus quality
      and performance improvement and customer service efforts. We conducted a
      retrospective review of complaints filed against a busy urban EMS agency over a 6
      year period. All complaints were included, totaled by season and by year, and
      categorized by originator and nature of the complaint. A total of 286 complaints
      were registered during the 6-year period, with an average of 48 per year and 9.3
      per 10,000 responses. The most common originators of complaints were patients
      (53%) followed by medical personnel (19%) and family members or friends (12%).
      Rude behavior accounted for 23% of the complaints registered, followed by
      technical skills (20%), transport problems (18%), and loss of belongings (13%).
      The identification of areas of dissatisfaction will allow focused quality and
      performance improvement programs directed at customer service and risk
      management.

PMID- 14654182
TI  - Critical illness at mass gatherings is uncommon.
AB  - Gatherings of large numbers of people at concerts, sporting events, and other
      occasions lead to an assembled population with a potential for a wide variety of
      illnesses and injuries. The collection of large numbers of people in a single
      location has led some authors to recommend the placement of resuscitation
      equipment or other medical services in close proximity to these activities. These
      recommendations not withstanding, data on the frequency of critical illness at
      mass gatherings (a group exceeding 1000 persons) are difficult to ascertain.
      Therefore, it was the purpose of this study to describe the incidence of critical
      illnesses among assembled populations at mass gatherings. An observational
      prospective study was conducted involving patient encounters at a large,
      multipurpose, indoor mass-gathering complex in Houston, Texas occurring between
      September 1, 1996 and June 30, 1997. Demographic, treatment, disposition and
      diagnostic data were analyzed in a computerized database. Of the 3.3 million
      attendants to the 253 events analyzed during the 10-month study period, there
      were 2762 (0.08%) patient encounters. Fifty-two percent were women. Mean age was
      32 +/- 15.6 years. Of these patients, 51.1% were patrons and the remaining
      patients were employees or contractors of the facility. A wide variety of illness
      was seen with trauma (39.5%), headache (31%), and other medical complaints
      (29.5%) being most frequent. Disposition of the patients included 95.3% being
      discharged to go back to the event and 2.2% being counseled to seek other medical
      attention. One hundred twenty-nine patients (4.7%) were referred to the Emergency
      Department (ED); of these, 70 were transferred for abrasions, lacerations, or
      skeletal injuries and 13 for chest pain. Of those referred to the ED, 50 (38.7%)
      patients were transported by ambulance and only 17.4% were admitted to telemetry,
      with none admitted to an ICU. It is concluded that critical illness at mass
      gatherings is infrequent, as seen in this study, with very few being admitted to
      telemetry and none to an ICU. Careful consideration of cost-benefit should occur
      when determining allocation of resources for these activities.

PMID- 14654183
TI  - Elevations of B-type natriuretic peptide in pulmonary embolism: a case series.
AB  - The use of B-type natriuretic peptide to diagnose congestive heart failure is
      becoming more frequent and widespread. We report five patients recently seen at
      our hospital who were diagnosed with pulmonary embolism and noted to have
      elevated B-type natriuretic peptide levels. We caution that elevations of B-type
      natriuretic peptide may in some patients have the potential to mislead clinicians
      if the diagnosis of pulmonary embolism is not considered.

PMID- 14654184
TI  - Combination pharmacotherapy with reduced-dose fibrinolytic and platelet GP
      IIb/IIIa inhibition.
AB  - Combination fibrinolytic and antiplatelet therapy regimens may provide a means of
      inducing rapid reperfusion in patients requiring myocardial salvage after an
      acute myocardial infarction (AMI). This article describes case histories and a
      therapeutic regimen combining reteplase (5 U + 5 U double bolus) and abciximab
      (0.25 mg/kg bolus + 0.125 microg/kg/min infusion to a maximum of 10 microg/min
      for 12 h) for AMI patients before percutaneous coronary intervention (PCI). This
      medication regimen was used in the Global Use of Strategies to Open Occluded
      Coronary Arteries (GUSTO) V clinical trial, for the medical treatment of AMI,
      resulting in decreased reinfarction rates with similar mortality and intracranial
      hemorrhage rates as compared to standard fibrinolytic therapy.

PMID- 14654186
TI  - An unusual cause of acute myocardial infarction.

PMID- 14654185
TI  - The use of benzodiazepines in the treatment of chest pain: a review of the
      literature.
AB  - Benzodiazepines, although not listed in the American Heart Association's
      guidelines for the treatment of chest pain, are often used to provide symptomatic
      relief to patients who experience chest pain. To investigate the utility of
      benzodiazepines in the treatment of chest pain, the pharmacologic actions and
      cardiovascular effects of benzodiazepines were reviewed. In addition, a
      literature search regarding the use of benzodiazepines to treat patients with
      chest pain was conducted. The results indicated that benzodiazepines reduce
      anxiety, pain, and cardiovascular activation. Benzodiazepines amplify gamma
      aminobutyric acid (GABA) throughout the central nervous system, and act more
      peripherally to reduce catecholamines. In addition, preliminary evidence
      indicates that benzodiazepines may cause coronary vasodilatation, prevent
      dysrhythmias, and block platelet aggregation, though further study is needed.
      Both non-cardiac chest pain (associated with musculoskeletal, esophageal,
      neurologic, and psychiatric conditions) and cardiac chest pain (associated with
      acute and chronic myocardial ischemia) seem to be effectively treated with
      benzodiazepines. Benzodiazepines are safe and well tolerated when administered
      alone or in combination with other medications. Moreover, the risk of dependence
      is minimal when benzodiazepines are prescribed on a short-term basis. Further
      study of benzodiazepines in the treatment of acute chest pain is needed to
      confirm these favorable actions and better define their use in the acute medical
      setting.

PMID- 14654187
TI  - Severe cervical spine distraction.

PMID- 14654188
TI  - Ten-year-old boy with a swollen knee: unusual cause of knee pain.

PMID- 14654189
TI  - Blossoming traumatic epidural hematoma.

PMID- 14654190
TI  - Management of chest pain patients.

PMID- 14654191
TI  - Risk and chest pain evaluation: inseparable?

PMID- 14654192
TI  - Use of benzodiazepines for chest pain: a new indication for an old drug?

PMID- 14654193
TI  - Critical illness at mass gatherings.

PMID- 14654194
TI  - Advanced life support courses for board-certified emergency physicians: lowering
      the standard of care?

PMID- 14654195
TI  - Chest pain.

PMID- 14654196
TI  - A fatal case of brucellosis displaying an atypical clinical course.

PMID- 14654197
TI  - Chronic acetaminophen toxicity.

PMID- 14654198
TI  - Retention of Pediatric Advanced Life Support (PALS) course concepts.
AB  - The purpose of this study was to measure, in a population of experienced state
      certified paramedics, the decline of Pediatric Advanced Life Support (PALS)
      course concepts during the 2-year recertification cycle recommended by the
      American Heart Association. The PALS course contains a written examination
      designed to measure understanding of course concepts. To successfully complete
      the course, a PALS course participant must achieve a minimum grade of 84% on this
      test. In our study, 99 experienced PALS-certified Advanced Life Support (ALS)
      providers completed a 70-question written test. Nested within this test were all
      of the PALS examination questions that the participants had previously passed to
      complete the PALS course. Each participant's PALS test questions were extracted
      and scored to obtain a "retest score" that measured retention of PALS course
      principles. These 99 dual-trained paramedic/firefighters comprised more than 90%
      of the staff of a countywide EMS system averaging 60,000 calls per year. Study
      participants averaged 10 years of ALS experience, and 3-4 pediatric patient calls
      per month. In this study, "pediatric patient" was defined as an individual 18
      years of age or less. Results revealed that 25 (25%) of the 99 providers achieved
      a minimum passing score of 84% or greater on the PALS retest. Another 40 (40%)
      scored within one standard deviation below the minimum passing score. Retest
      score was unaffected by years of ALS experience, number of pediatric patients
      seen per month, or by PALS Instructor status. The average retest score was 16
      points lower than the original test score. The original test score did not
      reliably predict a passing grade on the retest. We conclude that the average
      decline of PALS course principles is such that a 2-year retraining schedule is
      appropriate for prehospital personnel caring for an average of three to four
      pediatric patients per month.

PMID- 14654199
TI  - Joint position statement on the emergency care of children.

PMID- 14654202
TI  - Assessment of spatio-temporal gait parameters from trunk accelerations during
      human walking.
AB  - This paper studies the feasibility of an analysis of spatio-temporal gait
      parameters based upon accelerometry. To this purpose, acceleration patterns of
      the trunk and their relationships with spatio-temporal gait parameters were
      analysed in healthy subjects. Based on model predictions of the body's centre of
      mass trajectory during walking, algorithms were developed to determine spatio
      temporal gait parameters from trunk acceleration data. In a first experiment,
      predicted gait parameters were compared with gait parameters determined from
      ground reaction forces measured by a treadmill. In a second experiment, spatio
      temporal gait parameters were determined during overground walking. From the
      results of these experiments, it is concluded that, in healthy subjects, the
      duration of subsequent stride cycles and left/right steps, and estimations of
      step length and walking speed can be obtained from lower trunk accelerations. The
      possibility to identify subsequent stride cycles can be the basis for an analysis
      of other signals (e.g. kinematic or muscle activity) within the stride cycle.

PMID- 14654203
TI  - Acceleration threshold detection during short anterior and posterior
      perturbations on a translating platform.
AB  - Balance control systems have usually been studied under two conditions, during
      quiet standing or under large postural perturbations of a magnitude that requires
      a postural adjustment to prevent falling. Between these two extremes lie
      perturbations that can be repeated and measured while not forcing adaptive
      strategies from the postural control system. Unlike other studies of postural
      control, we employed very short translations with varying accelerations at the
      edge of psychophysical detectability. These perturbations were vibration-free
      anterior or posterior translations of the platform on which a subject stood.
      Using a full Latin-square design set of perturbations in the forward or backward
      direction, with a smooth or jerk acceleration profile, and of length 4 or 20 mm,
      were presented to five subjects. Perceptual peak acceleration thresholds were
      determined by an iterative psychophysical method that forced the subjects to
      choose in which of two sequential intervals that they perceived a stimulus to
      have been presented. The only factor found that significantly correlated with
      detection was perturbation length. The 4 mm peak thresholds averaged 14.51 mm/s2
      while 20 mm thresholds averaged 8.55 mm/s2. For the short perturbations employed
      in this study, detection of motion thus was dependent upon the magnitude of the
      acceleration, but it was independent of the acceleration profile (jerk versus
      smooth) or movement direction. By understanding the influences on the ability to
      perceptually detect motion underfoot, we can begin to understand what elements of
      the postural control system might be involved in the second-to-second control of
      balance.

PMID- 14654204
TI  - A comparison of external plantar loading and in vivo local metatarsal deformation
      wearing two different military boots.
AB  - The introduction of the M90 boot with a more flexible outer sole to military
      recruits in Sweden was accompanied by an increase in second metatarsal stress
      fractures. This study compared the new boot with the previous, stiffer model. A
      combination of external plantar pressure measurement (two subjects) and an in
      vivo measurement of dorsal metatarsal strain (six subjects) using strain gauge
      instrumented staples was implemented. Walking in both boot models resulted in
      increased plantar pressure under the heads of the lesser metatarsals and
      generally decreased loading under the remainder of the foot. Dorsal metatarsal
      tension increased for subjects wearing the new boot throughout a walking
      protocol.

PMID- 14654205
TI  - The effect of gait speed on lateral balance control during walking in healthy
      elderly.
AB  - The aim of this paper was to investigate the effect of speed dependency on
      lateral gait parameters. In 36 healthy elderly (mean age=72.5 years, S.D.=3.2
      years), walking at four different self-administered speeds, mediolateral trunk
      acceleration and step width (SW), but not step-width variability (SWV), were
      found to have quadratic relations to gait speed. Normalizing for speed by
      curvilinear interpolation, and controlling for subject characteristics, disclosed
      smaller SW (adjusted R2=0.41, P<0.001), but larger SWV (adjusted R2=0.26, P=0.01)
      with increasing age in multiple regression models. These relations were
      camouflaged at preferred speed.

PMID- 14654206
TI  - Centre of mass motion during gait in persons with myelomeningocele.
AB  - The movement of the centre of mass in the vertical and lateral directions during
      gait in children with myelomeningocele was analyzed. The children were classified
      into five groups depending on the successive paresis of lower limb muscle groups
      and compared to a control group. In the groups with dorsi- and plantarflexor
      weakness, the excursions increased and an anterior trend in the centre of mass
      was observed. In the groups with additional abductor paresis, the lateral
      excursion was highest and the vertical excursion low due to increased transverse
      and frontal motion and reduced sagittal motion. With further paresis of the hip
      extensors, the centre of mass was more posteriorly positioned due to compensatory
      trunk extension. Improved understanding of individual children's solutions to
      their muscle paresis can be obtained by visualizing the centre of mass relative
      to the pelvis. Centre of mass analyses in myelomeningocele offer an important
      complement to standard gait analysis.

PMID- 14654207
TI  - Energy cost, mechanical work, and efficiency of hemiparetic walking.
AB  - The energy cost of walking (C) in nine chronic hemiparetic patients was
      calculated by measuring the total mechanical work (Wtot) done by the muscles and
      the efficiency of this work production (eta). The energy cost was twice normal in
      slow walkers and 1.3 times greater in fast walkers. The increase in C was
      proportional to the increase in Wtot and eta was normal at around 20%, despite an
      increase in muscle tone and muscle co-contractions. This type of approach gives a
      greater understanding into how segmental impairments increase Wtot and C and
      contribute to a patient's disability.

PMID- 14654208
TI  - The clinical significance of electromyography normalisation techniques in
      subjects with anterior cruciate ligament injury during treadmill walking.
AB  - This study investigated the clinical interpretation of three electromyographic
      (EMG) normalisation techniques to detect neuromuscular alterations in patients
      diagnosed with anterior cruciate ligament knee injury during treadmill walking.
      The EMG signal was normalised using the mean value during the gait cycles (MEA),
      the maximum value during the gait cycles (MAX), and a maximum voluntary isometric
      contraction (MVC) test in 16 male and female subjects. The MAX method detected an
      increase in total muscle activity in the injured limb rectus femoris (11.6%;
      P=0.02) while the MVC method detected decreased injured limb gastrocnemius
      medialis (GM) overall muscle activity (34.4%; P=0.02). The MAX method identified
      decreased GM activity in three portions of the gait cycle. This study indicates
      the importance of choosing the appropriate normalisation technique since its
      choice will change outcome measures and subsequent clinical interpretation.

PMID- 14654209
TI  - The steady-state postural response to continuous sinusoidal galvanic vestibular
      stimulation.
AB  - Galvanic vestibular stimulation (GVS) applied between the mastoids during quiet
      standing elicits postural sway. The aim of this study was to characterize the
      postural sway response to continuous sinusoidal GVS across various stimulus
      frequencies and amplitudes. Binaural bipolar sinusoidal GVS was applied to the
      skin overlying the mastoid processes of 10 subjects while they stood on a force
      plate with eyes closed. The position of the center of pressure (COP) at the feet
      was recorded from a forceplate, while the head displacement was measured with a
      magnetic position tracking system. The stimulus conditions included four
      frequencies (0.1, 0.25, 0.45, and 1.1 Hz) and five peak amplitudes (0.05, 0.1,
      0.25, 0.5, and 1.0 mA). Each subject experienced one trial at each amplitude
      frequency pair. Additionally, each subject underwent three trials in which a dual
      frequency stimulus (0.1 plus 0.45 Hz at a peak of 0.5 mA each) was presented. The
      stimuli elicited sway in the frontal plane in all subjects, as evidenced by
      changes in the displacement of the COP and head. Sway magnitude decreased with
      increasing stimulus frequency and increased with increasing stimulus amplitude.
      However, the response magnitude saturated at higher stimulus amplitudes. Phase
      lag increased with increasing stimulus frequency. The response to the dual
      frequency stimulus was reduced at 0.1 Hz and nearly equal at 0.45 Hz in
      comparison with the single-frequency responses. This study suggests that the
      postural sway response is nonlinear due to saturation and violation of the
      principle of superposition.

PMID- 14654210
TI  - High- and low-ankle flexibility and motor task performance.
AB  - The effect of widely differing but normal passive ankle flexibility on function
      was investigated by using able-bodied males selected from the upper and lower
      tails of a group normally distributed for passive dorsiflexion (DF) flexibility.
      Ankle, knee and hip kinematics, and kinetics were quantified during stair
      descent, walking and standing up. The effect of DF flexibility was apparent
      during stair descent, but not in standing up or walking. Mean peak DF in stance
      phase of stair descent was 11.5 degrees lower for 'inflexible' compared with
      'flexible' subjects, but the net moment about the ankle at peak DF and the timing
      of peak DF were comparable between groups.

PMID- 14654211
TI  - The effect of foot wedging on electromyographic activity in the erector spinae
      and gluteus medius muscles during walking.
AB  - The use of foot orthoses for treatment of low back pain (LBP) has received some
      attention in the literature, mainly from a clinical or theoretical perspective.
      It has been proposed that this treatment alleviates pain by altering muscle
      activity in the area of the low back but there is no direct evidence of such an
      effect. The objective of this study was to determine the effects of different
      types of foot wedging on the bilateral surface electromyographic activity of
      erector spinae (ErSp) (L3 level) and gluteus medius (GlMed) of 13 participants
      without LBP. Activity in ErSp had a significantly earlier onset during the gait
      cycle with bilateral heel lifts and bilateral lateral forefoot wedging. GlMed
      activity had a significantly later onset with bilateral heel lifts, and with an
      unilateral heel lift on the ipsilateral side (P<0.0125). No significant amplitude
      changes were demonstrated in either muscle for any of the forms of wedging
      tested. These results show that foot wedging can produce measurable changes in
      timing of muscle activity within the low back and pelvis during the gait cycle.
      Further investigation is required to determine whether this effect contributes to
      the alleviation of LBP.

PMID- 14654212
TI  - Perturbation of the postural control system induced by muscular fatigue.
AB  - In this experiment, we induced muscular fatigue of ankle plantar-flexors to
      examine how it deteriorates the regulation of bipedal quiet upright standing.
      Postural stability was assessed in conditions with and without vision over 60 s
      period to examine not only classical postural variables (time- and frequency
      domain analyses), but also structural variables (stabilogram-diffusion analysis).
      Muscular fatigue was induced with repeated plantar-flexion of both legs. With
      muscular fatigue, subjects exhibited an increased postural sway (faster center of
      pressure (CP) velocity, and greater CP mean and median frequency) and a decreased
      long-term scaling exponent compared with the control conditions. The fatigue
      conditions, however, did not modify the range of oscillations and the variability
      of the postural oscillations around the mean position of CP. The effects of
      muscular fatigue were similar with eyes open and eyes closed. These results
      suggest that fatigue did induce some changes in the control mode of postural
      stability, but the detection/action capabilities of the sensorimotor system
      remained partly efficient when the ankle plantar-flexors were fatigued.
      Furthermore, the decreased long-term scaling exponent observed with fatigue
      suggests that the control of upright stance operates in a less stochastic and
      more antipersistent manner when fatigue is present (i.e. past and future
      behaviors were more negatively correlated and thus more tightly regulated).
      Altogether, the present results suggest that, compared with the no-fatigue
      conditions, fatigue places higher demands on the postural control system by
      increasing the frequency of actions needed to regulate the upright stance.

PMID- 14654213
TI  - Aging, muscle activity, and balance control: physiologic changes associated with
      balance impairment.
AB  - Older adults demonstrate increased amounts of postural sway, which may ultimately
      lead to falls. The mechanisms contributing to age-related increases in postural
      sway and falls in the elderly remain unclear. In an effort to understand age
      related changes in posture control, we assessed foot center-of-pressure (COP)
      displacements and electromyographic data from the tibialis anterior, soleus,
      vastus lateralis, and biceps femoris collected simultaneously during quiet
      standing trials from elderly fallers, elderly non-fallers, and healthy young
      subjects. Both traditional measures of COP displacements and stabilogram
      diffusion analysis were used to characterize the postural sway of each group.
      Regression analyses were used to assess the relationship between the COP measures
      and muscle activity. Elderly fallers demonstrated significantly greater amounts
      of sway in the anteroposterior (AP) direction and greater muscle activity during
      quiet standing compared with the young subjects, while elderly non-fallers
      demonstrated significantly greater muscle activation and co-activation compared
      with the young subjects. No significant differences were found between elderly
      fallers and elderly non-fallers in measures of postural sway or muscle activity.
      However, greater postural sway in both the AP and mediolateral (ML) directions
      and trends of greater muscle activity were found in those older adults who
      demonstrated lower scores on clinical measures of balance. In addition, short
      term postural sway was found to be significantly correlated with muscle activity
      in each of these groups. This work suggests that high levels of muscle activity
      are a characteristic of age-related declines in postural stability and that such
      activity is correlated with short-term postural sway. It is unclear whether
      increases in muscle activity preclude greater postural instability or if
      increased muscle activity is a compensatory response to increases in postural
      sway.

PMID- 14654214
TI  - Surface electromyography analysis for variable gait.
AB  - The surface electromyographic (SEMG) signal obtained during gait is often
      presented as the SEMG profile, the average SEMG activation pattern during one
      gait cycle. A disadvantage of this method is that it omits the step-to-step
      variability of the timing of the muscle activation patterns that might be
      relevant information as a performance measure of motor control and balance. In
      this paper, a method was used in which every step in the gait cycle could be
      analysed with respect to the timing of the muscle activation. For this purpose,
      the approximated generalised likelihood (AGLR) algorithm was implemented and
      tested. Results of the simulations show that the AGLR was much more accurate than
      a standard threshold criterion. Timing parameters could be calculated from a SEMG
      recording during gait and a measure for symmetry and coordination could be
      extracted. The amplitude distribution within and outside defined bursts is also
      presented to avoid the less precise classification into on and off patterns.

PMID- 14654215
TI  - Morpholino oligonucleotide-triggered knockdown reveals a role for maternal E
      cadherin during early mouse development.
AB  - We report that gene silencing via intracytoplasmic microinjections of morpholino
      modified antisense oligonucleotides is an effective and reproducible method to
      study both maternal and zygotic gene functions during early and late stages of
      mouse preimplantation development. The zygotic expression of the beta-geo
      transgene in the ROSA26 mouse strain could be inhibited until at least the early
      blastula stages. Thus morpholino-triggered gene inactivation appears to be a
      useful method to study the functional role of genes in preimplantation
      development. Using this approach, we have investigated a potential role of
      maternal expression of Cdh1, the gene encoding the cell-adhesion molecule E
      cadherin. Inhibition of translation of maternal E-cadherin mRNA causes a
      developmental arrest at the two-cell stage. BrUTP incorporation assays indicated
      that this developmental defect cannot be explained by a general failure in
      transcriptional activity. This defect is reversible since E-cadherin mRNA can
      rescue the affected embryos, suggesting that a functional adhesion complex,
      present at the junction between blastomeres, is a prerequisite for the normal
      development of the mouse preimplantation embryo. Our study thus reveals a
      previously unanticipated role of maternal E-cadherin during early stages of mouse
      development.

PMID- 14654216
TI  - Conservation of IGF2-H19 and IGF2R imprinting in sheep: effects of somatic cell
      nuclear transfer.
AB  - In different mammalian species, in vitro culture and manipulation can lead to
      aberrant fetal and peri-natal development. It has been postulated that these
      diverse abnormalities are caused by epigenetic alterations and that these could
      affect genes that are regulated by genomic imprinting. To explore this hypothesis
      relative to somatic cell nuclear transfer in sheep, we investigated whether the
      ovine H19-IGF2 and IGF2R loci are imprinted and analysed their DNA methylation
      status in cloned lambs. A comparison between parthenogenetic and control concepti
      established that imprinting at these two growth-related loci is evolutionarily
      conserved in sheep. As in humans and mice, IGF2R and H19 comprise differentially
      methylated regions (DMRs) that are methylated on one of the two parental alleles
      predominantly. In tongue tissue from 12 out of 13 cloned lambs analysed, the DMR
      in the second intron of IGF2R had strongly reduced levels of DNA methylation. The
      DMR located upstream of the ovine H19 gene was found to be similarly organised as
      in humans and mice, with multiple CTCF binding sites. At this DMR, however,
      aberrant methylation was observed in only one of the cloned lambs. Although the
      underlying mechanisms remain to be determined, our data indicate that somatic
      cell nuclear transfer procedures can lead to epigenetic deregulation at imprinted
      loci.

PMID- 14654217
TI  - Low-level ectopic expression of Fushi tarazu in Drosophila melanogaster results
      in ftz(Ual/Rpl)-like phenotypes and rescues ftz phenotypes.
AB  - The protein encoded by the Drosophila pair-rule gene fushi tarazu (ftz) is
      required for the formation of the even-numbered parasegments. Here we analyze the
      phenotypes of ectopic expression of FTZ and FTZ protein deletions from the
      Tubulin alpha1 (Tubalpha1) promoter. Fusion of ftz to the Tubalpha1 promoter
      resulted in low-level ectopic expression of FTZ relative to FTZ expressed from
      the endogenous ftz gene. The effects of ectopic expression of four FTZ proteins,
      FTZ(1-413) (full length wild-type FTZ), FTZ(delta257-316) (a complete deletion of
      the HD), FTZ(delta101-150) (a deletion that includes the major FTZ-F1 binding
      site) and FTZ(delta151-209) were determined. Ectopic expression of FTZ(1-413),
      FTZ(delta257-316) and FTZ(delta101-151) did not result in an anti-ftz phenotype;
      however, ectopic expression of FTZ(1-413), and FTZ(delta257-316) did result in a
      ftz(Ual/Rpl)-like phenotype. In addition, low-level ectopic expression of FTZ(1
      413) and FTZ(delta257-316) rescued ftz phenotypes. This was an important
      observation because the even-numbered parasegment pattern of FTZ expression is
      considered important for normal segmentation. Therefore, the rescue of ftz
      phenotypes by low-level FTZ expression in all cells of the embryo suggests that
      the even-numbered parasegment expression pattern of FTZ is not the sole factor
      restricting FTZ action. Low-level ectopic expression of FTZ(delta151-209)
      resulted in the anti-ftz phenotype and rescued hypomorphic ftz-f1 phenotypes
      indicating that FTZ(delta151-209) is a hyperactive FTZ molecule. Therefore, the
      region encompassing amino acids 151-209 of FTZ is required in some manner for
      repression of FTZ activity. These results are discussed in relation to the
      current understanding of the mechanism of FTZ action.

PMID- 14654219
TI  - Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via
      induction of Dlx5 and Cbfa1.
AB  - In the developing mammalian tooth, the cranial neural crest derived dental
      mesenchyme consists of the dental papilla and dental follicle. The dental papilla
      gives rise to odontoblasts and dental pulp and the dental follicle gives rise to
      the periodontium, including the osteoblasts that contribute to the alveolar
      process. The alveolar process is a specialized intramembranous bone that forms
      the primary support structure for the dentition. The Msx1 gene controls many
      aspects of craniofacial development, as evidenced by craniofacial abnormalities
      seen in Msx1(-/-) mice, including the arrest of tooth development and the absence
      of the alveolar bone. Previous studies demonstrated that ectopic expression of
      Bmp4, a downstream target of Msx1, in the Msx1(-/-) dental mesenchyme rescued
      alveolar bone formation. Here we confirm an early requirement of BMP activity for
      alveolar bone formation. We show that the expression of Cbfa1 and Dlx5, two genes
      encode transcription factors that are critical for bone differentiation, overlaps
      with that of Msx1 and Bmp4 in the developing tooth and alveolar process. We have
      demonstrated that Dlx5 and Cbfa1 expression is down-regulated in Msx1(-/-) dental
      mesenchyme and that Msx1 and Bmp4 expression are unaltered in Cbfa1(-/-) mice.
      These data place Dlx5 and Cbfa1 downstream from the Msx1/Bmp4 in the genetic
      pathway that regulates tooth development. Ectopic expression of Bmp4 in Msx1
      mutants restores the expression of Dlx5, but not Cbfa1, in the dental mesenchyme,
      and rescues the expression of both Dlx5 and Cbfa1 in the developing alveolar
      bone. Therefore, the early expression of Cfba1 in the dental mesenchyme appears
      dispensable for the development of the alveolar bone. Taken together with in
      vitro gene induction studies, our results demonstrate that BMP4 controls Dlx5
      expression in dental mesenchyme, and functions upstream to both Dlx5 and Cbfa1 to
      regulate alveolar bone formation during tooth development.

PMID- 14654218
TI  - Patterns and functions of STAT activation during Drosophila embryogenesis.
AB  - The JAK/STAT pathway mediates cytokine signaling in mammals and is involved in
      the function and development of the hematopoietic and immune systems. To
      investigate the biological functions of the JAK/STAT pathway during Drosophila
      development, we examined the tissue-specific localization of the tyrosine
      phosphorylated, or activated form of Drosophila STAT, STAT92E. Here we show that
      during Drosophila embryonic development STAT92E activation is prominently
      detected in multiple tissues and in different developmental stages. These tissues
      include the tracheal pits, elongating intestinal tracks, and growing axons. We
      demonstrate that stat92E mutants are defective in tracheal formation, hindgut
      elongation, and nervous system development. Conversely, STAT92E overactivation
      caused premature development of the tracheal and nervous systems, and over
      elongation of the hindgut. These results suggest that STAT activation is involved
      in proper differentiation and morphogenesis of multiple tissues during Drosophila
      embryogenesis.

PMID- 14654220
TI  - Specific modification of heparan sulphate is required for normal cerebral
      cortical development.
AB  - Proteoglycans are cell surface and extracellular matrix molecules to which long,
      unbranched glycosaminoglycan side chains are attached. Heparan sulphate, a type
      of glycosaminoglycan chain, has been proposed as a co-factor necessary for
      signalling by a range of growth factors. Here we provide evidence that loss of 2
      O-sulphation in heparan sulphate leads to a significant reduction in cell
      proliferation in the developing cerebral cortex. The gene encoding heparan
      sulphate 2-sulphotransferase (Hs2st) is expressed in embryonic cortex and
      histological analysis of mice homozygous for a null mutation in Hs2st indicated a
      reduction in the thickness of the embryonic cerebral cortex. Using 5'
      bromodeoxyuridine (BrdU) incorporation assays we found a reduction of
      approximately 40% in labelling indices of cortical precursor cells at E12.
      Comparison of the fates of cortical cells born on E13 and E15 in Hs2st(-/-)
      mutant and wildtype littermate embryos revealed no differences in the pattern of
      cell migration. Our findings suggest a critical role for 2-O-sulphation of
      heparan sulphate proteoglycan (HSPG) in regulating cell proliferation during
      development of the cerebral cortex, perhaps through the modulation of cellular
      responses to growth factor signalling.

PMID- 14654221
TI  - Cloning and functional analysis of ascidian Mitf in vivo: insights into the
      origin of vertebrate pigment cells.
AB  - The microphthalmia-associated transcription factor (Mitf) is a basic-helix-loop
      helix-leucine zipper (bHLH-ZIP) transcription factor essential for the
      development and function of all melanin-producing pigment cells in vertebrates.
      To elucidate the evolutionary history of Mitf and the antiquity of its
      association with pigment cells, we have isolated and characterized HrMitf, a sole
      member of the Mitf-TFE bHLH-ZIP subfamily in the ascidian Halocynthia roretzi.
      Maternal HrMitf mRNA is detected in the fertilized egg and in the animal
      hemisphere from 4-cell stage through the gastrula stage. From the neurula through
      the early tailbud stage, HrMitf is preferentially expressed in the pigment
      lineage cells that express the lineage-specific melanogenesis genes tyrosinase
      (HrTyr) and Tyrp. Overexpression of HrMitf induced ectopic expression of HrTyr
      enzyme activity in mesenchymal cells where the same enzyme activity was induced
      by overexpression of HrPax3/7, suggesting that a part(s) of the Pax3-Mitf
      tyrosinase gene regulatory cascade seen in vertebrate melanocytes is operative
      during ascidian embryogenesis. We also show HrMitf and mouse Mitf-A, a Mitf
      isoform abundantly expressed in pigmented epithelial cells, share similar
      functional characteristics. These results suggest antiquity of the association of
      the Mitf-TFE subfamily with pigment cells and may support the idea that
      acquisition of multiple promoters (isoforms) by an ancestral Mitf gene has
      allowed the evolution of multiple pigment cell types.

PMID- 14654222
TI  - Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity:
      evidence for the importance of de novo ceramide synthesis in TNF-alpha signaling.
AB  - Measuring the cell death induced by tumor necrosis factor (TNF-alpha) in L929
      cells, we discovered for the first time that L-cycloserine, an established
      inhibitor of serine palmitoyltransferase, as well as DL-threo-dihydrosphingosine
      (threo-DHS, threo-sphinganine) significantly protected against TNF-alpha-induced
      cytotoxicity. Under the same conditions sphingosine and DL-erythro
      dihydrosphingosine (erythro-DHS) did not change TNF-alpha-induced cytotoxicity,
      thus underlining the specificity of threo-DHS. In serine-labeled cells, newly (de
      novo) synthetized labeled ceramide was significantly diminished by threo-DHS
      alone or together with TNF-alpha, which makes the (dihydro) ceramide synthase the
      likely target of threo-DHS. These results suggest the decisive role of ceramide
      de novo synthesis in TNF signaling.

PMID- 14654223
TI  - Roc, a Ras/GTPase domain in complex proteins.
AB  - We identified a novel group of the Ras/GTPase superfamily, termed Roc, that is
      present as domain in complex proteins together with other domains, including
      leucine-rich repeats (LRRs), ankyrin repeats, WD40 repeats, kinase domains,
      RasGEF and RhoGAP domains. Roc is always succeeded by a novel 300-400-amino-acid
      long domain, termed COR. Proteins with Roc/COR are present in prokaryotes,
      Dictyostelium, plants and metazoa.

PMID- 14654224
TI  - Cytokinin-induced differentiation of human myeloid leukemia HL-60 cells is
      associated with the formation of nucleotides, but not with incorporation into DNA
      or RNA.
AB  - Cytokinins are important purine derivatives that act as hormones to control many
      processes in plants. Cytokinins such as isopentenyladenine (IPA), kinetin and
      benzyladenine were very effective at inducing the granulocytic differentiation of
      human myeloid leukemia HL-60 cells. The metabolism of cytokinins to their
      nucleotides was closely associated with cytokinin-induced differentiation and
      growth inhibition. When the cells were incubated with [14C]-benzyladenine,
      radioactivity was significantly incorporated into RNA and DNA. However, the
      radioactive nucleotides in RNA or DNA were adenine nucleotides, not benzyladenine
      nucleotides, suggesting that cytokinins were not incorporated into RNA and DNA.
      The benzyladenine nucleotides were not stably released into the medium in intact
      form. Cytokinins effectively induced a phosphorylated (active) form of mitogen
      activated protein kinase (MAPK). MAPK activation was necessary for cytokinin
      induced differentiation, because PD98059, an inhibitor of MAPK kinase, suppressed
      the differentiation induced by cytokinins. These results suggest that cytokinin
      nucleotides themselves play an important role in inducing the differentiation of
      HL-60 cells.

PMID- 14654225
TI  - Modulation of phospholipase D-mediated phosphatidylglycerol formation by
      differentiating agents in primary mouse epidermal keratinocytes.
AB  - The major component of the epidermis, keratinocytes, must continuously
      proliferate and differentiate to form the mechanical and water permeability
      barrier of the skin. Our previous data have suggested a potential role in these
      processes for phospholipase D (PLD), an enzyme that hydrolyzes phospholipids to
      generate phosphatidic acid. In the presence of primary alcohols, PLD also
      catalyzes a transphosphatidylation reaction to produce phosphatidylalcohols, and
      this characteristic has been exploited to monitor the activity of PLD in intact
      cells. In this report, PLD was demonstrated to utilize the physiological alcohol
      glycerol to form phosphatidylglycerol (PG) in vitro. In intact primary murine
      epidermal keratinocytes treated for 24 h with elevated extracellular Ca(2+)
      levels, but not 1,25-dihydroxyvitamin D(3), incubation with radioactive glycerol
      resulted in an increase in PLD-mediated radiolabeled PG production. This effect
      was dose-dependent and biphasic, with maximal PG formation detected after
      exposure to an intermediate (125 microM) Ca(2+) concentration. Furthermore, the
      biphasic nature of the response was due, in part, to a corresponding biphasic
      change in glycerol uptake. Finally, short-term treatment of keratinocytes with
      phorbol 12-myristate 13-acetate (PMA) failed to increase PG synthesis and
      inhibited glycerol uptake. Since (1) PMA is reported to activate PLD-1 to a
      greater extent than PLD-2, (2) 1,25-dihydroxyvitamin D(3) increases the
      expression/activity of PLD-1 in keratinocytes, and (3) PLD-2 is co-localized with
      a glycerol channel in keratinocyte membrane microdomains, we speculate that
      radiolabeled PG production from radioactive glycerol is a measure of PLD-2
      activation in these cells. Our results also suggest that PLD-mediated PG
      synthesis may be regulated at the level of both PLD activity and alcohol
      substrate availability via changes in glycerol uptake.

PMID- 14654226
TI  - Hepatocyte growth factor activates several transduction pathways in rat
      pancreatic acini.
AB  - The receptor of hepatocyte growth factor (HGF), c-met induces different
      physiological responses in several cell types. Little is known about the role of
      HGF in exocrine pancreas. However, abnormal HGF signaling has been strongly
      implicated in pancreatic tumorigenesis and association of HGF with pancreatitis
      has been demonstrated. We have studied the presence of c-met and activation of
      their intracellular pathways associated in rat pancreatic acini in comparison
      with cholecystokinin (CCK) and epidermal growth factor (EGF). C-met expression in
      rat exocrine pancreas was identified by immunohistochemistry and
      immunoprecipitation followed by Western analysis. Tyrosine phosphorylation of c
      met is strongly stimulated as well as kinase pathways leading to ERK1/2 cascade.
      HGF, but not CCK or EGF, selectively caused a consistent increase in the amount
      of p85 regulatory subunit of PI3-K present in anti-phosphotyrosine
      immunoprecipitates. Downstream of PI3-K, HGF increased Ser473 phosphorylation of
      Akt selectively, as CCK or EGF did not affect it. HGF selectively stimulated
      tyrosine phosphorylation of phosphatase PTP1D. HGF failed to promote the well
      known CCK effects in pancreatic acini such as amylase secretion and intracellular
      calcium mobilization. Although HGF shares activation of ERK1/2 with CCK, we
      demonstrate that it promotes the selective activation of intracellular pathways
      not regulated by CCK or EGF. Our results suggest that HGF is an in vivo stimulus
      of pancreatic acini and provide novel insight into the transduction pathways and
      effects of c-met/HGF in normal pancreatic acinar cells.

PMID- 14654227
TI  - Recovery from heat shock injury by activation of Na+-glucose cotransporter in
      renal epithelial cells.
AB  - Exposure of cells or organs to sublethal physical or chemical stresses induces
      disruption of cellular structures and functions. Here, we examined whether Na(+)
      glucose cotransporter (SGLT1) is involved in the recovery from heat shock (HS)
      injury in porcine renal epithelial LLC-PK(1) cells. Recovery from HS (42 degrees
      C for 3 h, then 37 degrees C for 12 h) increased SGLT1 activity, assessed by
      [14C]alpha-methyl glucopyranoside uptake, and a maximal transport rate (V(max))
      from 2.4 to 5.9 nmol/mg protein/30 min, but did not alter an apparent affinity
      constant (K(m)). Protein distribution of SGLT1 in apical membrane fraction was
      also increased after recovery from HS without changing in total membrane
      fraction. Membrane integrity assessed by calcein accumulation was decreased by
      HS, and then returned to basal level. This recovery was inhibited by phloridzin,
      a potent SGLT1 inhibitor, and nonmetabolizable glucose analogues. Anti
      transforming growth factor-beta 1 (TGF-beta 1) antibody inhibited both elevation
      of SGLT1 distribution in apical membrane and recovery of calcein accumulation
      induced by HS. Taken together, HS increases in the number of SGLT1 protein in
      apical membrane mediated via TGF-beta 1 signaling pathway. The increase of
      glucose uptake is necessary to repair plasma membrane integrity.

PMID- 14654228
TI  - Nuclear localization domains in human thyroid transcription factor 2.
AB  - Thyroid transcription factor-2 (TTF2) is a nuclear protein involved in
      morphogenesis and gene expression in thyroid gland, belonging to the family of
      the forkhead/winged-helix transcription factors. In the present study we have
      investigated the sequence determinants for transport and accumulation into the
      nucleus of the TTF2 protein. By transient expression of fusion proteins
      constructed by joining different parts of TTF2 to the reporter gene of the
      jellyfish green fluorescent protein (GFP) and, in a separate set of deleted
      constructs, the glutathione S-transferase (GST) coding sequence, we have
      demonstrated that a basic amino acid stretch present at both ends of the DNA
      binding domain is a bona fide nuclear localization signal (NLS). We have analyzed
      the subcellular localization of deleted GFP-GST-TTF2 fusion proteins and have
      shown that residues inside the forkhead domain (FHD) contributed to the complete
      nuclear TTF2 protein accumulation. Furthermore, by means of GST binding assays we
      have shown that distinct TTF2 fragments, containing the NLS, were able to bind
      the nuclear import receptor importin alpha. Taken together, our results provide
      the first documentation about nuclear targeting of a forkhead protein containing
      two identical NLS signal flanking the DNA-binding domain.

PMID- 14654229
TI  - Calcitonin gene-related peptide partly protects cultured smooth muscle cells from
      apoptosis induced by an oxidative stress via activation of ERK1/2 MAPK.
AB  - Oxidative stress induced by a glucose/glucose oxidase (G/GO) generator system
      dose-dependently decreased the viability of cultured vascular smooth muscle cells
      (VSMC) as estimated by MTT assay. Cell death was induced in 40% of cells exposed
      to 0.2 IU/ml of the free radical generating mixture. Annexin-V labeling, Hoechst
      staining together with DNA laddering demonstrated that apoptosis was responsible
      for this cell loss. Pretreatment of the cells with 10(-8) M calcitonin gene
      related peptide (CGRP) significantly attenuated the damaging effect of the
      oxidative stress. Indeed, cell viability was estimated to be 80% in CGRP-treated
      group, instead of 60% in absence of CGRP treatment. This protective effect of
      CGRP was antagonized by 8-37 CGRP, an antagonist of CGRP-1 receptors, whereas it
      was not reproduced by amylin, a CGRP analogue. As indicated by the reduction in
      Hoechst staining and in DNA laddering, CGRP prevented the onset of apoptosis. We
      also demonstrated that the peptide significantly up-regulated the activation of
      ERK1/2 and P38 kinases. Inhibitors of the kinases prevented the protective effect
      of CGRP. We conclude that CGRP antagonizes oxidative stress-induced apoptosis by
      up-regulating MAP kinase activation and that activation of these kinases was
      necessary to protection.

PMID- 14654230
TI  - Substance P induces TNF-alpha and IL-6 production through NF kappa B in
      peritoneal mast cells.
AB  - The neuropeptide Substance P (SP) is an important mediator of
      neuroimmunomodulatory activity. The aim of this study is to elucidate the
      mechanism used by SP to promote increased production of pro-inflammatory
      cytokines in fresh isolated rat peritoneal mast cells (rPMC). We have
      demonstrated that SP induces production of interleukin-6 (IL-6) in rPMC through
      the PI-3K, p42/44 and p38 MAP kinase pathways. SP-stimulated rPMC also exhibited
      an enhanced nuclear translocation of the nuclear factor kappa B (NF kappa B). The
      tumour necrosis factor-alpha (TNF-alpha) and IL-6 production was completely
      inhibited by using (E)-4-hydroxynonenal (HNE) as an inhibitor of I kappa B-alpha
      and -beta phosphorylation. Further, TNF-alpha and IL-6 expression was
      significantly inhibited by the oligonucleotides (ODNs) containing the NF kappa B
      element (NF kappa B decoy ODNs) but not by the scrambled control ODNs. These
      findings indicate that the NF kappa B pathway is involved in the transcriptional
      regulation of the TNF-alpha and IL-6 overexpression in primary SP-stimulated mast
      cells.

PMID- 14654231
TI  - Cell-to-cell variability in the differentiation program of human megakaryocytes.
AB  - Differentiation of CD34(+) stem/progenitor cells into megakaryocytes is thought
      to be a uniform, unidirectional process, in which cells transform step by step
      from less differentiated precursor stages to more differentiated megakaryocytes.
      Here we propose the concept and present evidence based on single-cell analysis
      that differentiation occurs along multiple, partially asynchronous routes. In all
      CD34(+) cells cultured with thrombopoietin, surface appearance of glycoprotein
      IIIa (GPIIIa) preceded that of GPIb, indicating that the expression of these
      glycoproteins occurs in a timely ordered manner. Cellular F-actin content
      increased in parallel with GPIb expression. Only cells that expressed GPIb were
      polyploid, pointing to co-regulation of GPIb expression, actin cytoskeleton
      formation and polyploidization during megakaryocytopoiesis. On the other hand,
      most progenitor cells responded to thrombin but not to thromboxane A(2) analogue
      by rises in cytosolic [Ca(2+)](i). The appearance of thromboxane-induced
      responses during megakaryocytopoiesis was not strictly linked to glycoprotein
      expression, because cells showed responsiveness either before or after GPIb
      expression. The same non-strictly sequential pattern was observed for
      disappearance of the Ca(2+) response by prostacyclin mimetic; in some
      megakaryocytes it occurred before and in others after GPIb expression. Thus,
      megakaryocytic differentiation follows along independent routes that are either
      strictly sequential (GPIIIa and GPIb expression) or proceed at different
      velocities (Ca(2+) signal regulation).

PMID- 14654232
TI  - Effects of the antimicrobial peptide PGLa on live Escherichia coli.
AB  - The activity of PGLa, an antimicrobial peptide isolated from hemocytes of frog
      skin and its secretions on living Escherichia coli, was investigated by imaging
      the cells with atomic force microscopy (AFM) in physiological conditions and by
      measuring its cellular stiffness. The treatment of bacteria with the
      antimicrobial peptide PGLa in the culture medium had two stages. The first was
      characterized by the loss of surface stiffness and consequent loss of bacteria
      topographic features and the formation of micelles probably originating from the
      disruption of the outer membrane. The formation of outer membrane originated
      micelles is in agreement with the carpet-like mechanism of action proposed for
      antimicrobial peptides of the magainin family. The peptide action also resulted
      in the removal of bacterial pili. In a second stage there was further damage
      which resulted in total cell rupture. The addition of Mg(2+) ions prior to
      peptide treatment partially inhibited the effects of PGLa on bacteria. This
      result suggests that PGLa interacts with the outer membrane by displacing Mg(2+)
      from LPS, inserting itself into the bilayer and cross-bridging the negative
      charges of LPS lipids as proposed in the self-promoted pathway mechanism. The
      peptide effect on the bacteria was compared to the activity of the chelating
      agent EDTA that damages the bacterial outer membrane by removing Mg(2+) ions.

PMID- 14654233
TI  - C-type natriuretic peptide decreases soluble guanylate cyclase levels by
      activating the proteasome pathway.
AB  - Natriuretic peptides (NP) activate particulate guanylate cyclase (pGC) and nitric
      oxide (NO) activates soluble guanylate cyclase (sGC). Both guanylate cyclases
      catalyse the formation of the same second messenger, cyclic guanosine 3',5'
      monophosphate (cGMP), which activates the cGMP-dependent protein kinases (PKG).
      PKG then starts a signalling cascade that mediates many cardiovascular and renal
      effects, such as smooth muscle relaxation and diuresis. Many cell types possess
      both sGC and pGC. Because both GC-cGMP systems play complementary roles, an
      interaction between the two pathways might represent an important physiological
      control mechanism. In this report we demonstrate an interaction between the two
      pathways. C-type natriuretic peptide (CNP) decreased the beta-subunit of sGC (sGC
      beta) steady-state protein levels and enzymatic activity in cultured human
      mesangial cells (HMC) in a time- and dose-dependent manner. This down-regulation
      was not dependent on changes in sGC-beta mRNA levels. Treatment of the cells with
      the stable cGMP analogue 8-Br-cGMP or the phosphodiesterase type-5 inhibitor
      Zaprinast produced the same down-regulatory effect. Inhibition of PKG or
      proteasome activity prevented the CNP-induced reduction of sGC-beta protein
      levels and activity. Taken together, these results demonstrate that pGC
      activation induces a post-transductional down-regulation of sGC by a mechanism
      involving PKG and the proteasome pathway.

PMID- 14654234
TI  - Glycosylation profile of integrin alpha 3 beta 1 changes with melanoma
      progression.
AB  - Glycosylation of integrins has been implicated in the modulation of their
      function. Characterisation of carbohydrate moieties of alpha(3) and beta(1)
      subunits from non-metastatic (WM35) and metastatic (A375) human melanoma cell
      lines was carried out on peptide-N-glycosidase F-released glycans using matrix
      assisted laser desorption ionization mass spectrometry (MALDI-MS). beta(1)
      integrin subunit from both cell lines displayed tri- and tetraantennary
      oligosaccharides complex type glycans, but only in A375 cell line was the
      sialylated tetraantennary complex type glycan (Hex(7)HexNAc(6)FucSia(4)) present.
      In contrast, only alpha(3) subunit from metastatic cells possessed beta1-6
      branched structures. Our data indicate that the beta(1) and alpha(3) subunits
      expressed by the metastatic A375 cell line carry beta1-6 branched structures,
      suggesting that these cancer-associated glycan chains may modulate tumor cell
      adhesion by affecting the ligand binding properties of alpha(3)beta(1) integrin.
      In direct ligand binding assays, alpha(3)beta(1) integrin from both cell lines
      binds strongly to fibronectin and to much lesser degree to placental laminin. No
      binding to collagen IV was observed. Enzymatic removal of sialic acid residues
      from purified alpha(3)beta(1) integrin stimulates its adhesion to all examined
      ECM proteins. Our data suggest that the glycosylation profile of alpha(3)beta(1)
      integrin in human melanoma cells correlates with the acquisition of invasive
      capacity during melanoma progression.

PMID- 14654235
TI  - Dexamethasone responsive element in the rat Na, K-ATPase beta1 gene coding
      region.
AB  - The Na, K-ATPase plays an essential role in active alveolar epithelial fluid
      resorption. In fetal and adult alveolar epithelial cells, glucocorticoids (GC)
      increase Na, K-ATPase activity, mRNA levels, and transcription rate of the
      beta(1) subunit. In this study, we describe a glucocorticoid responsive element
      (GRE) in the coding region of the rat Na, K-ATPase beta(1) gene in a rat lung
      epithelial cell line. Transient transfection experiments with the beta(1) subunit
      coding region with or without the 5' and 3' untranslated regions demonstrated
      responsiveness to dexamethasone induction and also identified a GRE at +434 in
      exon IV. The +434 GRE conferred dexamethasone responsiveness in a heterologous
      thymidine kinase promoter irrespective of its orientation to the beta(1)
      promoter. Transcriptional upregulation by dexamethasone was abolished in +434
      mutants. Electrophoretic mobility shift assays (EMSA) demonstrated specific
      binding of nuclear proteins to the +434 GRE and the presence of the GC receptor.
      This specific binding was inhibited by a GRE previously described in the rat Na,
      K-ATPase beta(1) gene at -631. In conclusion, we identified a GRE at +434 in the
      exon IV of the rat Na, K-ATPase beta(1) gene.

PMID- 14654236
TI  - Novel vanadium-binding proteins (vanabins) identified in cDNA libraries and the
      genome of the ascidian Ciona intestinalis.
AB  - Ascidians, especially those belonging to the suborder Phlebobranchia, can
      accumulate high levels of vanadium. Vanadium-binding proteins (vanabins) were
      first isolated from a vanadium-accumulating ascidian, Ascidia sydneiensis samea,
      and then the vanabins were cloned, their expression was studied, and metal
      binding assays were conducted. In order to unravel the mechanism of vanadium
      accumulation, we searched for vanabin-like genes in other animals, including
      other ascidians. A database search revealed five groups of cDNAs that encoded
      vanabin-like proteins in another ascidian, Ciona intestinalis. The genes encoding
      C. intestinalis vanabins, CiVanabin1 to CiVanabin5, were clustered in an 8.4-kb
      genomic region. The direction of transcription of each gene was identical and
      each gene had a single intron. All the C. intestinalis vanabins were cysteine
      rich, and the repetitive pattern of cysteines closely resembled that of A.
      sydneiensis samea vanabins. Using immobilized metal ion affinity chromatography
      (IMAC), we found that a recombinant protein of at least one of the C.
      intestinalis vanabins (CiVanabin5) bound to vanadium(IV) ions.

PMID- 14654237
TI  - Two exonic elements in the flanking constitutive exons control the alternative
      splicing of the alpha exon of the ZO-1 pre-mRNA.
AB  - The 240-bp alpha exon of the tight junction (TJ) protein ZO-1 pre-mRNA is
      alternatively spliced. Expression of both ZO-1alpha+/ZO-1alpha- isoforms results
      in hermetic TJs, and these become leaky when ZO-1alpha- expression prevails. The
      alpha exon inclusion/skipping mechanism was studied by in vivo RT-PCR splicing
      assays in neural and epithelial cells, utilizing a canine minigene construct
      containing the alpha exon, and the flanking introns and exons. Inclusion of the
      alpha exon always occurs in wild-type MDCK cells and it is detectable in
      transfected HeLa cells. However, the alpha exon is skipped in transfected neural
      cells. Accordingly, both 5' and 3' splice sites surrounding the alpha exon appear
      to be suboptimal and no cis-acting splicing control elements were found in this
      exon. Deletion analysis revealed an 83-bp splicing enhancer in the downstream
      exon and a 35-bp splicing silencer at the beginning of the upstream exon. In
      epithelial cells all constructs rendered alpha exon inclusion. We conclude that,
      in neural cells, skipping of the alpha exon depends on two antagonistic exonic
      elements located in the flanking constitutive exons.

PMID- 14654238
TI  - Effects of additional sequences directly downstream from the AUG on the
      expression of GFP gene.
AB  - We have studied the expression of the green fluorescent protein (GFP) gene to
      gain more understanding of the effects of additional nucleotide triplets (codons)
      downstream from the initiation codon on the translation of the GFP mRNA in CHO
      and Cos1 cells. A leader sequence of six consecutive identical codons (GUG, CUC,
      AGU or UCA) was introduced into a humanized GFP (hm gfp) gene downstream from the
      AUG to produce four GFP gene variants. Northern blot and RT-PCR analysis
      indicated that mRNA transcription from the GFP gene was not significantly
      affected by any of the additional sequences. However, immunoblotting and FACS
      analysis revealed that AGU and UCA GFP variants produced GFP at a mean level per
      cell 3.5-fold higher than the other two GFP variants and the hm gfp gene. [35S]
      Methionine labeling and immunoprecipitation demonstrate that GFP synthesis was
      very active in UCA variant transfected-cells, but not in GUG variant and hm gfp
      transfected-cells. Moreover, proteasome inhibitor MG-132 treatment indicated that
      the GFPs encoded by each of the GFP variants and the hm gfp were equally stable,
      and this together with the comparable mRNA levels observed for each construct
      suggested that the different steady-state GFP concentrations observed reflected
      different translation efficiencies of the various GFP genes. In addition, the CUC
      GFP variant, when transiently transfected into CHO or COS-1 cells, did not
      produce any GFP expressing cells (fully green cells), and the GUG variant
      produced GFP expressing cells less than 10%, while AGU and UCA GFP variants up to
      30-35% in a time course study from 8 to 36 h posttransfection. Analysis of the
      potential secondary structure of the GFP variant mRNAs especially in the
      translation initiation region suggested that the secondary structure of the GFP
      mRNAs was unlikely to explain the different translation efficiencies of the GFP
      variants. The present findings indicate that a change of the initiation context
      of the GFP gene by addition of extra coding sequence can alter the translation
      efficiency of GFP mRNA, providing a means of more efficient expression of GFP in
      eukaryotic cells.

PMID- 14654239
TI  - Changes in mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and
      cholesterol 7 alpha-hydroxylase in chickens.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and cholesterol 7 alpha
      hydroxylase (CYP7A1), essential enzymes of cholesterol synthesis and excretion,
      respectively, were isolated from a chicken liver cDNA library. When their
      recombinant proteins were overexpressed in HNK293 cells, corresponding enzyme
      activities were observed. The complete open reading frames of MHGR and CYP7A1
      contained (i) 2625 base pairs (bp), predicting a protein of 875 amino acids, and
      (ii) 1539 bp, predicting a protein of 513 amino acids, respectively. By Northern
      blot analysis, chicken HMGR mRNA expression was detected in most tissues
      examined, however, the highest levels were found in liver, brain and ileum.
      CYP7A1 mRNA was detected only in the liver. Changes in chicken HMGR and CYP7A1
      mRNA expression with nutritional state were examined and were shown to respond to
      certain nutritional treatments, i.e. fast refeeding and cholesterol
      supplementation. HMGR and CYP7A1 mRNA levels were significantly increased with
      maturation (i.e. egg producing), when compared to immature chickens. However,
      these stimulations were not associated with estrogen, although this does enhance
      triacylglycerol and very low density lipoprotein secretion by the chicken liver.
      The present study is the first to report the molecular characterization of HMGR
      and CYP7A1, key enzymes of cholesterol metabolism in avian species.

PMID- 14654240
TI  - Nucleosome positioning signals and potential H-DNA within the DNA sequence of the
      imprinting control region of the mouse Igf2r gene.
AB  - The imprinting control region within the second intron of the mouse Igf2r gene
      contains a CpG island comprising direct repeats, an imprinting box and the Air
      antisense promoter which is blocked by the methylation imprint on the active
      maternal allele. We have investigated the structural features of this DNA,
      including a mapping of all nucleosome positioning signals within the nucleotide
      sequence. A discrete series of strong positioning signals distinguished the
      direct repeat region from the much more diverse positioning capacity of the
      sequence encompassing the known regulatory elements. At only a few locations did
      CpG methylation modulate the use of this positioning information. Direct effects
      upon histone-DNA interactions are therefore unlikely to contribute significantly
      to the means by which the imprint may establish allele-specific chromatin
      architecture and determine Air expression. A strand-specific obstruction to DNA
      polymerase was observed between the repeat and regulatory regions. The same
      region adopts triple-stranded H-DNA structures in supercoiled DNA, according to
      pH and divalent cation exposure. Methylation did not modulate the occurrence or
      form of this structure under the conditions tested. This finding nevertheless
      adds to the repertoire of potential H-DNA structures found in the vicinity of
      regulatory sequences-here, in an imprinting context.

PMID- 14654241
TI  - A functional ISRE is required for myeloid transcription of the p47(phox) gene.
AB  - Expression of p47(phox), a component of the phagocytic NADPH oxidase, is both
      tissue-specific and developmentally regulated. We have investigated transcription
      from the p47(phox) gene promoter by reporter gene analysis of myeloid PLB985
      cells stably transfected with a series of p47(phox) promoter constructs. Stable
      transfection with constructs containing up to 3100 bp of proximal promoter
      sequence demonstrated that as little as 144 bp of proximal promoter sequence was
      able to direct significant reporter gene activity in myeloid cells, but not in
      HeLa cells. Mutation of a previously uncharacterised interferon-stimulated
      response element (ISRE) consensus located at positions -104 to-116, or of an
      established binding site for the Ets family transcription factor, PU.1 (located
      at positions -39 to -44), abolished transcription in stably transfected myeloid
      cells. Electrophoretic mobility shift analysis (EMSA) with myeloid cell nuclear
      extracts demonstrated that an oligonucleotide containing the p47(phox) ISRE
      consensus was able to compete binding at another bona fide ISRE. Complexes formed
      on the p47(phox) ISRE itself were competed by other ISRE consensus sequences. We
      conclude that transcription of p47(phox) in myeloid cells requires a functional
      ISRE in addition to the previously identified PU.1 binding site.

PMID- 14654242
TI  - Genomic organization, promoter, amino acid sequence, chromosomal localization,
      and expression of the human gene for CORS-26 (collagenous repeat-containing
      sequence of 26-kDa protein).
AB  - The murine gene for CORS-26 is located on mouse chromosome 15A2 and its
      expression has been reported to be restricted to fibroblasts, cartilage and
      kidney. Here, the complete genomic organization of the corresponding human CORS
      26 gene with exon/intron boundaries and exon-specific primer combinations is
      presented. Additionally, a 1.2 kb fragment of the TATA box-containing promoter
      region was cloned and analyzed for putative transcription factor binding sites.
      The deduced amino acid sequence is presented completely. Northern blot analysis
      using a human multiple-tissue cDNA panel demonstrated expression of human CORS-26
      mRNA in colon and small intestine. Additionally, RT-PCR analysis revealed
      expression of CORS-26 mRNA in placenta, fibroblasts and white adipose tissue. The
      chromosomal localization of the human CORS-26 gene was mapped to human chromosome
      5p by fluorescence in situ hybridization (FISH). In humans, chromosomal
      imbalances on chromosome 5p were reported to be involved in the pathogenesis of
      osteosarcoma. Therefore, a human bone tumor cDNA panel was investigated and a
      strong CORS-26 mRNA expression was found in osteosarcoma, chondroblastoma and
      giant cell tumor. The present data provide the basis for further investigation of
      CORS-26 gene regulation in the context of mesenchymal tissue development and in
      the pathogenesis of bone or skeletal disease.

PMID- 14654243
TI  - Molecular cloning of PP2Ceta, a novel member of the protein phosphatase 2C
      family.
AB  - We have cloned a novel member of the mouse protein phosphatase 2C family,
      PP2Ceta. Sequence analysis suggests that PP2Ceta, PP2Czeta and NERPP-2C
      constitute a unique subgroup of the PP2C family. PP2Ceta had extremely low
      activity against alpha-casein compared with PP2Calpha and was localized mainly in
      cell nuclei, suggesting that PP2Ceta dephosphorylates a unique nuclear protein(s)
      in the cells.

PMID- 14654244
TI  - Human ileal bile acid-binding protein promoter and the effects of CDX2.
AB  - The ileal bile acid-binding protein (IBABP) is important for the reabsorption of
      bile salts in the distal small intestine. Studies with the human IBABP gene
      (FABP6, on chromosome 5q33.3-q34) defined the major transcription start site and
      identified conserved elements. A consensus element for the caudal-related
      homeobox factor CDX2 was functional in gel-shift assays and in transfection
      experiments.

PMID- 14654245
TI  - Palmitate-induced Ca2+-signaling in pancreatic beta-cells.
AB  - Free fatty acids (FFA) have been proposed to participate in the regulation of
      insulin release from pancreatic beta-cells (beta-cells). As a rise in cytosolic
      free Ca2+ ([Ca(2+)]i) is a key event for the stimulation of insulin secretion,
      the effects of saturated FFA on [Ca2+]i were investigated. Palmitate was used as
      a reference compound and [Ca2+]i was measured in single fura-2 loaded HIT-T15 and
      in primary mouse beta-cells. Stimulation of single beta-cells with palmitate (100
      microM) caused either repetitive Ca2+ transients or a plateau-like rise in
      [Ca2+]i. In HIT-T15 and in mouse beta-cells, the number of palmitate-responsive
      cells, and the amplitude of the palmitate-induced Ca2+-signals were dependent on
      the extracellular glucose concentration. In Ca2+-free medium palmitate (100
      microM) caused only 1 or 2 Ca2+ transients indicating mobilization of Ca2+ from
      internal stores. Withdrawal of external Ca2+, the addition of voltage-sensitive
      Ca2+ channel (VSCC) blockers, as well as the K(ATP)-channel opener diazoxide (100
      microM) reversibly blocked the palmitate-induced cytosolic Ca2+ responses. This
      demonstrates that Ca2+ influx through VSCC of the L-type coupled to membrane
      depolarization through closure of K(ATP)-channels are crucial for a sustained
      Ca2+-signal in response to palmitate. Methyl palmoxirate (100 microM) and 2
      bromopalmitate (100 microM), which both inhibit transport of acyl-CoA into the
      mitochondria, reversibly blocked the palmitate-induced Ca2+-signals in HIT-T15 as
      well as in primary mouse beta-cells. By contrast, cerulenin (100 microM), an
      inhibitor of protein acylation, had no effect on the palmitate-induced changes in
      [Ca2+]i, which suggests that mitochondrial palmitate metabolism is required for
      eliciting the Ca2+-signals. Simultaneous measurement of [Ca2+]i and the
      mitochondrial membrane potential (DeltaPsi) revealed palmitate-induced
      depolarization of DeltaPsi which demonstrates that palmitate does not enhance
      mitochondrial ATP production. Therefore mitochondrial signals other than ATP
      appear to be generated from palmitate metabolism that underly the palmitate
      induced Ca2+-signals in pancreatic beta-cells.

PMID- 14654246
TI  - Estrogen and androgen regulation of plasma membrane calcium pump activity in
      immortalized distal tubule kidney cells.
AB  - The ATP dependent plasma membrane calcium pump (PMCA) is a regulator of renal
      calcium reabsorption. The effect of estrogen and dihydrotestosterone to increase
      the activity of the PMCA in membrane vesicle preparations from a distal tubule
      cell line was investigated. 17beta Estradiol (10(-10)M) increased PMCA activity
      (1.5 +/- 0.2-fold increase compared to control) with 24 h, but not 1 or 5 h, of
      exposure, an effect that was blocked by the addition of the estrogen antagonist
      ICI 164384. alpha Estradiol did not increase PMCA activity. Dihydrotestosterone
      (10(-11)M ) resulted in a dose dependent increase in PMCA activity (1.5+/-0.1
      fold increase compared to control) with 24h, but not 1 or 5h, of exposure, an
      effect that was blocked by the androgen receptor agonist flutamide. Testosterone
      (10(-5)M) also increased PMCA activity (1.9+/-0.3-fold increase compared to
      control). Neither estrogen nor dihydrotestosterone increased PMCA protein
      expression in MDBK cells, indicating that these hormones increase PMCA activity
      by regulating PMCA activity rather than PMCA expression. These results
      demonstrate receptor dependent stimulatory effects of both estrogen and
      dihydrotestosterone to increase PMCA activity. and have significance for our
      understanding of estrogen and androgen deficient states on calcium transport.

PMID- 14654247
TI  - Regulation of FSHbeta and GnRH receptor gene expression in activin receptor II
      knockout male mice.
AB  - To examine in vivo, the local effects of inhibins and activins within the
      anterior pituitary, independent of their endocrine effects exerted from the
      gonad, in mediating FSH homeostasis, we used castrated knockout mice lacking
      either inhibin alpha or activin receptor II (ACVR2) alone or in combination.
      Compared to castrated wild-type (WT) mice, FSHbeta mRNA levels in the pituitaries
      of Acvr2 null mice were significantly downregulated in the absence of gonadal
      feedback. FSHbeta mRNA levels were not significantly higher in the pituitaries of
      castrated inhibin alpha null mice compared to those in Acvr2 null mice and
      remained the same in the pituitaries of castrated double mutant mice lacking both
      inhibin and ACVR2. In contrast to FSHbeta mRNA expression changes, pituitary FSH
      content was significantly reduced in Acvr2 null mice whereas it was only slightly
      upregulated in inhibin alpha null mice. Combined absence of both ACVR2 signaling
      and inhibins caused a decrease in FSH content compared to that in the absence of
      inhibins alone. These changes in pituitary content were in parallel to those in
      serum FSH levels in these three groups of castrated mice, suggesting that the
      unopposed actions of locally produced inhibins are dominant over those effects
      mediated by ACVR2 signaling to regulate FSH biosynthesis and secretion. Thus, our
      in vivo results demonstrate that within the pituitary, locally produced activins
      and inhibins exert their actions at distinct phases of FSH homeostasis. In an
      independent set of experiments, we tested whether in vivo signaling via ACVR2 is
      necessary for hypothalamic GnRH biosynthesis and for GnRH receptor expression.
      Our results demonstrate that in contrast to previous in vitro studies, signaling
      through ACVR2 is neither required for hypothalamic synthesis of GnRH peptide nor
      for expression of GnRH receptors in the anterior pituitary. We conclude that
      within the hypothalamic-pituitary short loop, ACVR2 signaling is critical only
      for FSH homeostasis and not for GnRH biosynthesis or induction of pituitary GnRH
      receptor expression. Our studies confirm the importance of using in vivo genetic
      models for studying regulation of the hypothalamic-pituitary-gonadal axis.

PMID- 14654248
TI  - Analysis of CREM-dependent gene expression during mouse spermatogenesis.
AB  - The transcription factors CREM, CREB, and ATF-1 constitute a subfamily of beta
      Zip transcription factors. Several different kinase cascades regulate the
      activity of these proteins. The activator splice-isoform CREMtau is specifically
      and highly expressed in post-meiotic germ cells during mouse spermatogenesis.
      Male mice lacking CREMtau expression are sterile because of stage-specific arrest
      of sperm maturation as the spermatids undergo apoptosis. In order to characterize
      the genes that are controlled by CREM during post-meiotic differentiation of
      round spermatids, we compared the expression levels of mRNA prepared from testes
      of wild-type and CREM-deficient mice by suppression subtractive hybridization
      (SSH) and affymetrix oligonucleotide arrays. A set of 956 unique sequences found
      in the CREM SSH library was further characterized by generating stage-specific
      expression profiles during spermatogenesis by hybridization with cDNA from pre
      pubertal mice at defined stages of spermatogenesis using nylon DNA arrays. The
      resulting expression profiles were arranged in a linear order according to
      similarity in their profile shapes to find co-regulation of functionally related
      genes. Our data shows that a large number of genes are transcriptionally
      activated in round spermatids when CREM activity is maximal, including functional
      groups like transcription factors, proteins involved in signal transduction, and
      metabolic enzymes, therefore providing novel information of post-meiotic
      expression of many known as well as novel genes that are either directly or
      indirectly influenced by CREM expression.

PMID- 14654249
TI  - A rapid screening assay for inhibitors of 11beta-hydroxysteroid dehydrogenases
      (11beta-HSD): flavanone selectively inhibits 11beta-HSD1 reductase activity.
AB  - A rapid screening assay for chemicals inhibiting 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) type 1 or type 2 using lysates from stably transfected
      cells was developed. Here, we tested a series of environmental chemicals for anti
      11beta-HSD activities. Inhibition of 11beta-HSD2, which may cause cortisol
      dependent activation of the mineralocorticoid receptor with sodium retention and
      hypertension, was observed for several compounds, with diethylcarbamate being the
      most potent inhibitor (IC50 6.3 microM). Abietic acid inhibited both 11beta-HSD1
      (IC50 27 microM for reduction and 2.8 microM for oxidation) and 11beta-HSD2 (IC50
      12 microM). Our results demonstrate for the first time that flavanone selectively
      inhibits 11beta-HSD1 reductase activity: this enzyme being considered as
      essential for the local activation of glucocorticoids and representing a
      potential target for the therapeutic treatment of diabetes type 2. Flavanone and
      2'-hydroxyflavanone efficiently inhibited reductive (IC50 18 and 10 microM) but
      not oxidative activity. We observed a reduced inhibitory effect of hydroxylated
      flavanone derivatives and of flavones containing a double-bond between atom C2
      and C3. Flavanone was specific for 11beta-HSD1 and did not inhibit 11beta-HSD2.
      Our results reveal that a variety of environmental compounds exert distinct
      inhibitory effects on 11beta-HSD1 and 11beta-HSD2, opening the possibility for
      selectively modulating local cortisone/cortisol availability in vivo.

PMID- 14654250
TI  - Translation of the human angiotensin II type 1 receptor mRNA is mediated by a
      highly efficient internal ribosome entry site.
AB  - Activation of the angiotensin II type 1 receptor (AT1R) is closely involved in
      the pathogenesis of cardiovascular disease. The human AT1R (hAT1R) mRNA splice
      variants have long 5'-untranslated regions (5'-UTRs) ranging from 272 to 414 bp
      that have the potential to form stable secondary structures. In this study, we
      show that the 5'-UTR of hAT(1)R mRNAs contains an internal ribosome entry site
      (IRES) located within the first 40 bp of the proximal end of exon 1. Experiments
      utilizing the hAT1R 5'-UTR as a molecular decoy demonstrate a reduction in IRES
      activity of approximately 50%. This inhibition is most efficient for the hAT1R
      IRES suggesting that a defined set of trans-factors are required to initiate
      translation through this cis-element. Translation initiation from the hAT1R IRES
      appears to be physiologically relevant since IRES activity was maintained during
      serum starvation, a cellular stress known to inhibit cap-dependent translation.
      These results suggest that cap-independent translation initiation by internal
      ribosome entry may represent an important mechanism for the regulation of hAT1R
      expression.

PMID- 14654251
TI  - Maternal-fetal transfer of endocrine disruptors in the induction of Calbindin-D9k
      mRNA and protein during pregnancy in rat model.
AB  - Estrogenic compounds may influence the growth, differentiation and function in
      many target tissues, especially in the female reproductive tract during
      pregnancy. The present study was designed to investigate whether CaBP-9k
      expression in the maternal tissues and fetal uterus is altered following maternal
      treatment with diethylstilbestrol (DES), 17beta-estradiol (E2), 4-tert
      octylphenol (OP), nonylphenol (NP) and bisphenol A (BPA) during late pregnancy.
      The expression level of CaBP-9k mRNA in maternal uterus significantly increased
      when treated with a high dose (600 mg/kg BW per day) of OP and NP. Interestingly,
      the expression level of CaBP-9k mRNA in extra-embryonic membrane decreased in a
      dose-dependent manner, suggesting that the expression level of CaBP-9k mRNA in
      the fetal membrane may be differentially regulated when compared to the
      expression of CaBP-9k in maternal uterus. In parallel with CaBP-9k mRNA level, a
      high dose (600 mg/kg) of OP and BPA resulted in an increase of CaBP-9k protein in
      maternal uterus and low dose of OP and NP increased the expression level of CaBP
      9k protein in the placenta. High doses of BPA (400 and 600 mg/kg) resulted in an
      increase of CaBP-9k protein in maternal uterus and placenta, indicating that
      these estrogenic compounds may affect both maternal uterus and placenta in the
      induction of CaBP-9k mRNA and/or protein. In parallel with the expression level
      of CaBP-9k, mRNA decreased in extra-embryonic membrane, treatment with OP (400
      and 600 mg/kg) resulted in a significant decrease of CaBP-9k protein in this
      tissue, suggesting that both CaBP-9k mRNA and protein may be conversely regulated
      by OP in extra-embryonic membrane when compared to other tissues. Treatment with
      OP, NP, and BPA induced a significant increase of CaBP-9k mRNA in fetal uterus,
      indicating that maternally injected estrogenic compounds may transfer directly
      from placenta to fetus in the induction of fetal uterus CaBP-9k gene. Taken
      together, we demonstrated for the first time that maternally injected estrogenic
      compounds resulted in an increase of CaBP-9k mRNA and/or protein in the maternal
      tissues (uterus and placenta) and fetal uterus during late pregnancy, suggesting
      that placenta may not be a reliable barrier against these estrogenic compounds
      for fetal health.

PMID- 14654252
TI  - Affinity purification and diagnostic use of TSH receptor autoantibodies from
      human serum.
AB  - Purification of TSH receptor autoantibodies (TRAb) from the serum of patients
      with Graves' disease (GD) might help to elucidate the nature of these disease
      causing autoantibodies. We describe here for the first time the successful
      affinity purification of human TRAb. Affinity purification was performed in a
      four step procedure with human recombinant TSH receptor (TSH-R) expressed in K562
      cells. Purification from six different serum pools from patients with GD and two
      individual sera (one with only thyroid stimulating antibodies (TSAb) one with
      only thyroid blocking antibodies (TBAb)) resulted in a purity of 39.2+/-3.8 IU/mg
      TRAb or 25.7+/-2.1 microg IgG/IU (about 3.5-13.7 microg TRAb/ml serum). The
      average enrichment based on the respective original serum was 3420-fold (range
      1200-10,000). The kDa of the purified TRAb were in the range of 0.7-2.6 x 10(
      10)M. All purified TRAb (except from the TBAb serum which showed blocking
      activity) showed a more than 1000-fold stronger stimulation in the TSAb bioassay
      based on the IgG content than the original serum, and similar stimulation based
      on international units (IU/l) TRAb. When labelled purified TRAb were used in a
      competitive assay as tracer instead of bovine TSH, their binding to the human
      recombinant TSH-R on tubes was displaced by 99 of 100 GD sera (selected for TBII
      activity). Correlation to the standard TSH tracer was r=0.92. Interestingly, the
      use of TRAb tracer derived from a patient with TSAb and a patient with TBAb gave
      virtually identical results (r=0.93) with these patients, suggesting similar if
      not identical binding sites for both TRAb subtypes. In conclusion, this is the
      first report on the purification of human TRAb from the serum of patients with
      GD. The purified TRAb are of low concentration with high affinity, strong TBII
      and TSAb activity. Further characterisation may allow new insights in TRAb
      epitope localisation, the pathology of GD and the differences between TSAb and
      TBAb. Also, their use as tracer in a competitive assay is the first report on a
      completely homogenous assay with high sensitivity for TSH-R autoantibodies.

PMID- 14654254
TI  - Botulinum toxin type A influences stump pain after limb amputations.

PMID- 14654255
TI  - Re: definitions related to the medical use of opioids.

PMID- 14654257
TI  - Ketamine in the management of chronic pancreatic pain.

PMID- 14654258
TI  - Clonazepam as an adjuvant analgesic in patients with cancer-related neuropathic
      pain.

PMID- 14654259
TI  - Chronic lymphocytic leukemia resembling metastatic bone disease-- an unusual
      manifestation.

PMID- 14654260
TI  - The Cancer Care Monitor: psychometric content evaluation and pilot testing of a
      computer administered system for symptom screening and quality of life in adult
      cancer patients.
AB  - Technology is making the routine screening of symptoms and the measurement of
      quality of life (QoL) more feasible at the point of care. However, most existing
      symptom screening scales and QoL measures were not developed for clinical use and
      were not formatted and validated for administration through computerized mediums.
      The Cancer Care Monitor (CCM) is a symptom-based scale developed for
      administration on pen-based computers. This study is an initial evaluation of the
      reliability and validity of the CCM. Three samples of adult outpatients provided
      ratings on 38 physical, psychological, and functional oriented items of the CCM
      that comprise six symptom scales and one global QoL index. All additive scales
      are converted to normalized T scores. Reliability was examined through internal
      consistency and confirmatory factor analysis. Convergent and divergent validity
      were examined by comparing CMM scores to established measures of corresponding
      constructs and physician judgments. Alternative forms reliability was established
      by comparing paper and pencil administration with computer administration.
      Internal consistency reliability and factor analyses confirmed the structure of
      the CCM as comprising six primary symptom scales and one global QoL index.
      Internal consistency reliabilities ranged from 0.80 to 0.89. The pattern of
      correlations between CCM scales and established measures supported the convergent
      and divergent validity of the CCM scales. Alternate forms reliability based on
      paper and computer forms of the CCM scales was high. Patients indicated a
      preference for the computer-administered version. Results suggest that CCM items
      can be scored as a reliable and valid measure of constructs related to physical,
      psychological, and functional status, and global health-related QoL in adult
      cancer patients. Future studies should replicate and further evaluate the
      properties of the CCM, especially in relation to clinical utility.

PMID- 14654261
TI  - Japanese version of the MD Anderson Symptom Inventory: a validation study.
AB  - Cancer patients frequently suffer from a myriad of symptoms. The development and
      application of comprehensive assessment tools is essential to the effective
      management of these symptoms. The M.D. Anderson Symptom Inventory (MDASI),
      developed in English, is a brief, self-rating multiple symptom assessment scale
      that consists of 13 symptom items and 6 interference items. We examined the
      validity and reliability of the Japanese version of this scale (MDASI-J) by
      evaluating 252 randomly selected cancer patients. They were asked to self
      administer the MDASI-J and the European Organization for Research and Treatment
      of Cancer QLQ-C 30. Construct, criterion, convergent and discriminant validity,
      and reliability of the MDASI-J were evaluated and compared with corresponding
      data obtained in the previous study conducted in the United States. The results
      indicated that the MDASI-J is a valid and practical measure for assessing
      multiple symptoms in Japanese cancer patients. Both factor analysis and cluster
      analysis showed the consistency of the statistical structure of the English and
      Japanese versions, indicating the cross-cultural validity of the scale.

PMID- 14654262
TI  - Paroxetine in the treatment of severe non-dermatological pruritus: a randomized,
      controlled trial.
AB  - Severe pruritus may be an idiopathic phenomenon or associated with advanced
      systemic disease. It is one of the most distressing and difficult to treat
      symptoms. Uncontrolled studies have suggested that, in patients experiencing
      severe pruritus, paroxetine appeared to have a rapid anti-pruritic effect. This
      study was a prospective double-blind, randomized within patient comparison of
      paroxetine and placebo. The intensity of pruritus was measured subjectively with
      a numerical analogue scale. The primary endpoint of the trial was the mean
      pruritus score, measured for seven days after randomization and after cross-over.
      The secondary endpoint was individual global response to the treatment. Response
      was defined as at least 50% reduction of intensity of pruritus in the last three
      days of the treatment period vs. baseline. Adverse effects and patient
      satisfaction and preferences were also recorded. Twenty-six patients were
      included in the study; 17 of them had solid tumors, 4 had hematological
      malignancies and 5 had various nonmalignant or idiopathic conditions. Eight
      patients had drug-induced pruritus (none opioid-induced), 7 patients had
      paraneoplastic pruritus and 3 had cholestatic pruritus. After a run-in period,
      patients were randomly assigned to treatment with 20 mg paroxetine or placebo.
      The crossover took place after 7 days. Two patients discontinued treatment
      because of adverse effects of paroxetine. Twenty-four patients treated with
      paroxetine had lower pruritus intensity scores over the 7 treatment periods
      (mean+/-SE=5.2+/-0.32) as compared to placebo (mean+/-SE=6.0+/-0.32). Mean
      difference between placebo and paroxetine was 0.78 (95% CI=0.37-1.19). Nine of
      twenty-four patients (37.5%) fulfilled criteria of response. The onset of anti
      pruritic action was observed usually after 2-3 days, irrespective of the order of
      treatment. The outcome of this study indicates that paroxetine is effective in
      the treatment of severe pruritus of non-dermatological origin.

PMID- 14654263
TI  - Fatigue after treatment for malignant and benign bone and soft tissue tumors.
AB  - Fatigue has been mentioned as an important complaint in several groups of disease
      free patients after curative treatment for cancer. However, it has never been
      investigated in a sample of patients who have been treated for a bone or soft
      tissue tumor in the past. In the current study, these patients participated.
      Measurement included posted questionnaires at baseline and at follow-up (two
      years later). Baseline results indicated that fatigue is a severe problem for 28%
      of the investigated patients. Percentages were equal for patients who were
      treated for malignant or benign tumors. Fatigue complaints seem to be most severe
      for patients who finished treatment relatively recently, and for patients who had
      to undergo more than one operation. In addition, fatigue was associated with
      several psychological and physical variables. At follow-up, the majority of all
      patients who were severely fatigued at baseline continued to be severely
      fatigued. Severe fatigue at follow-up was predicted by oncological complications
      after initial treatment, less optimism, and more somatization. It can be
      concluded that fatigue is an important problem for more than a quarter of a
      sample of patients who have been treated for a malignant or benign bone or soft
      tissue tumor in the past.

PMID- 14654264
TI  - Analysis and treatment of different types of neuropathic cancer pain.
AB  - Neuropathic pain is a major problem in the treatment of cancer pain. We performed
      a retrospective analysis of 213 cancer patients with neuropathic pain treated by
      a pain service following the World Health Organization guidelines for relief of
      cancer pain. Of these, 79% presented with nerve compression pain, 16% with nerve
      injury pain, and 5% with sympathetically-maintained pain. Whereas nerve
      compression and nerve injury pain were caused most frequently by cancer growth,
      sympathetically-maintained pain was caused most frequently by cancer treatment.
      There were no significant differences in the use of analgesics, the mean pain
      intensity, or the efficacy of analgesic treatment among the three groups. Nerve
      injury pain and sympathetically-maintained pain were treated more frequently with
      adjuvant analgesics, especially antidepressants and anticonvulsants. The variety
      of different neuropathic pain syndromes should be separated in future studies of
      the efficacy of different treatment approaches.

PMID- 14654265
TI  - Anemia at the end of life: prevalence, significance, and causes in patients
      receiving palliative care.
AB  - While data exist on the prevalence and causes of anemia in defined groups of the
      elderly, information on palliative care patients is limited. Compared to actively
      treated oncology patients, for whom anemia treatment has demonstrated improved
      quality of life and symptom alleviation, studies of treatment outcomes in
      palliative care patients are limited. Knowledge of the extent and causes of
      anemia in palliative care patients is needed, as correction of anemia in these
      patients could potentially improve their physical, emotional, and cognitive
      functioning. In the present study, clinical data and blood test results of 105
      patients meeting specific eligibility criteria were examined to estimate the
      prevalence of anemia and investigate its causes. Ninety-five (90.5%) patients had
      advanced cancer. Based on World Health Organization criteria, anemia was found in
      77% of men (Hb <130 g/l) and 68.2% of women (Hb <120 g/l). The diagnosis was
      anemia of chronic disease in 76.7% of women and 46.8% of men. Patients with
      prostate cancer had a significantly lower mean Hb level (P=0.007) and more
      evidence of bone metastases (P=0.0007) than those with other cancers. Neutrophil
      hypersegmentation, suggesting occult folate deficiency, was present in 28.6% of
      patients, being more common in those with major weight loss (58.3%) than those
      with moderate (37%) or mild/no weight loss (26%) (P=0.019). The findings suggest
      that anemia is highly prevalent in the palliative care setting. Although anemia
      of chronic disease is most common, occult folate deficiency may be more prevalent
      than previously suspected. The findings suggest that a low serum folate level is
      an insensitive marker of occult folate deficiency. A randomized controlled trial
      of folic acid treatment is proposed.

PMID- 14654266
TI  - Celiac plexus block for pancreatic cancer pain: factors influencing pain,
      symptoms and quality of life.
AB  - Neurolytic celiac plexus block (NCPB) is claimed to be an effective method of
      pain control for pancreatic cancer pain. However, the factors that may influence
      long-term analgesia, adverse effects, and quality of life after performing NCPB
      have never been determined. In a prospective multicenter study, 22 patients who
      underwent NCPB were followed until death. Numerous parameters other than pain and
      symptom intensity were evaluated, including age, gender, initial site of cancer,
      sites of pain, possible peritoneal involvement, technique, and oncologic
      interventions. Indices were calculated to determine the opioid consumption ratio
      (EAS) and the trend of opioid escalation (OEI). NCPB was effective in reducing
      opioid consumption and gastrointestinal adverse effects for at least 4 weeks. In
      the last four weeks prior to death, there was the typical trend of increasing
      symptom intensity common to the terminal cancer population. None of the factors
      studied influenced the analgesic effectiveness of NPCB. NPCB, performed by
      skilled clinicians, regardless of the technique chosen, is a safe and useful
      means that should be considered as an adjuvant to common analgesic regimens at
      any stage, as it may allow the reduction of the visceral component of pancreatic
      pain that may prevail in certain phases of the illness. The analgesic and
      symptomatic effect of NCPB is presumably advantageous for about four weeks. A
      possible factor interfering with long-term outcome includes the capacity of
      cancer to involve the celiac axis, which can distort the anatomy and prevent
      neurolytic spread, or modify the pain mechanisms. Outcomes are strongly based on
      individual variation.

PMID- 14654270
TI  - [Coincidence, reflection and dialogue].

PMID- 14654271
TI  - [Local reunion of plastic surgery, Rio de Janeiro, July 31-August 2, 2003].

PMID- 14654272
TI  - [Right of reply. Revol M. Paidoyer for the saving of what remained of individual
      liberty in the profession named "liberal"].

PMID- 14654273
TI  - Platinum group elements in the environment and their health risk.
AB  - Accumulation of platinum group elements (PGEs) in the environment has been
      increased over the time. Catalytic converters of modern vehicles are considered
      to be the main sources of PGE pollution, since the correlation is between the
      Pt:Rh ratios in various environmental compartments and in converter units. The
      present literature survey shows that the concentration of these metals has
      increased significantly in the last decades in diverse environmental matrices;
      like airborne particulate matter, soil, roadside dust and vegetation, river,
      coastal and oceanic environment. Generally, PGEs are referred to behave in an
      inert manner and to be immobile. However, there is an evidence of spread and
      bioaccumulation of these elements in the environment. Platinum content of road
      dusts can be soluble, consequently, it enters the waters, sediments, soil and
      finally, the food chain. The effect of chronic occupational exposure to Pt
      compounds is well-documented, and certain Pt species are known to exhibit
      allergenic potential. However, the toxicity of biologically available
      anthropogenic Pt is not clear. Hence, there is a need to study the effect on
      human health of long-term chronic exposure to low levels of Pt compounds.

PMID- 14654274
TI  - Human lead exposure in England from approximately 5500 BP to the 16th century AD.
AB  - Lead concentration and isotope ratio data are presented for the tooth enamel of
      77 individuals buried in England and spanning approximately 5000 years from the
      Neolithic until the 16th century AD. Whereas other tissues may be affected by
      diagenesis in the burial environment, the Pb concentration of tooth enamel is
      directly related to childhood exposure. This record is preserved post-mortem and
      over archaeological time. Tooth enamel Pb concentrations in the prehistoric
      period appear to be variable within the range 0.04 to approximately 0.4 ppm, with
      occasional higher levels. The Romano-British and medieval periods show a marked
      increase in Pb exposures with enamel concentrations reaching up to approximately
      40 ppm. These exposures would today be associated with industrial pollution.
      Exposures appear to be highly variable compared with modern people, however, with
      many medieval individuals having very low enamel Pb concentrations comparable
      with prehistoric people. Lead isotope data refine this picture. We distinguish
      between the diverse isotopic ratios we believe to be characteristic of 'natural'
      exposure to Pb-from geological sources via the diet-and the much narrower
      isotopic range characteristic of exposure to technological Pb from ore sources.
      Taken together the data suggest that the maximum concentrations associated with
      'non-technological' exposure at any period are approximately 0.5-1.0 ppm, similar
      to that reported for modern people in England.

PMID- 14654275
TI  - Radiocaesium and natural gamma emitters in mushrooms collected in Spain.
AB  - Mushrooms can accumulate heavy metals in general, including radionuclides found
      in the nature. However, little attention has been paid to the radioactive content
      of mushrooms collected in Spain and the dose for the population due to their
      ingestion. To address this, we analysed the contents of 137Cs, 40K, 226Ra and 7Be
      present in different species of mushrooms, according to their genus and
      nutritional mechanism. We observed that mycorrhizal mushrooms accumulate 137Cs
      more than saprophytes, and vice versa for 7Be. 40K and 226Ra are accumulated to
      the same degree by the two groups of mushrooms. We estimated the dose due to
      ingestion of mushrooms in Spain to be 2 microSv/year, and the contribution of 40K
      and 226Ra to be generally greater than that of 137Cs. The contribution of 137Cs
      to the dose was calculated by taking into account the results of an experiment
      carried out under the controlled laboratory conditions, which showed that
      approximately 98% of 134Cs was associated with the readily digestible fraction of
      the mushrooms.

PMID- 14654276
TI  - Using a linked soil model emulator and unsaturated zone leaching model to account
      for preferential flow when assessing the spatially distributed risk of pesticide
      leaching to groundwater in England and Wales.
AB  - Although macropore flow is recognized as an important process for the transport
      of pesticides through a wide range of soils, none of the existing spatially
      distributed methods for assessing the risk of pesticide leaching to groundwater
      account for this phenomenon. The present paper presents a spatially distributed
      modelling system for predicting pesticide losses to groundwater through micro-
      and macropore flow paths. The system combines a meta version of the mechanistic,
      dual porosity, preferential flow pesticide leaching model MACRO (the MACRO
      emulator), which describes pesticide transport and attenuation in the soil zone,
      to an attenuation factor leaching model for the unsaturated zone. The development
      of the emulator was based on the results of over 4000 MACRO model simulations.
      Model runs describe pesticide leaching for the range of soil types, climate
      regimes, pesticide properties and application patterns in England and Wales.
      Linking the MACRO emulator to existing spatial databases of soil, climate and
      compound-specific loads allowed the prediction of the concentration of pesticide
      leaching from the base of the soil profile (at 1 m depth) for a wide range of
      pesticides. Attenuation and retardation of the pesticide during transit through
      the unsaturated zone to the watertable was simulated using the substrate
      attenuation factor model AQUAT. The MACRO emulator simulated pesticide loss in 10
      of 12 lysimeter soil-pesticide combinations, for which pesticide leaching was
      shown to occur and also successfully predicted no loss from 3 soil-pesticide
      combinations. Although the qualitative aspect of leaching was satisfactorily
      predicted, actual pesticide concentrations in leachate were relatively poorly
      predicted. At the national scale, the linked MACRO emulator/AQUAT system was
      found to predict the relative order of, and realistic regional patterns of,
      pesticide leaching for atrazine, isoproturon, chlorotoluron and lindane. The
      methodology provides a first-step assessment of the potential for pesticide
      leaching to groundwater in England and Wales. Further research is required to
      improve the modelling concept proposed. The system can be used to refine regional
      groundwater monitoring system designs and sampling strategies and improve the
      cost-effectiveness of the measures needed to achieve 'good status' of groundwater
      quality as required by the Water Framework Directive.

PMID- 14654277
TI  - Nova Scotia moose mystery--a moose sickness related to cobalt- and vitamin B12
      deficiency.
AB  - A wasting, debilitating disease with uncertain aetiology affecting moose (Alces
      alces americana) in Eastern North America has been reported repeatedly ever since
      the 1910s. Despite the intensive studies during 1930-1960s the cause of the
      sickness could not be established. In the 1960s a parasitic nematode
      (Parelaphostrongylus tenuis) was reported as constituting a probable explanation
      for the sickness, although several clinical and pathological signs remained
      unexplained. In Sweden, a moose disease with similar signs, has been shown to be
      caused by molybdenosis resulting from a nutritional imbalance. The findings of
      this investigation were applied in Nova Scotia to determine trace element
      concentrations in tissues from indigenous moose. Co deficiency was found in about
      half of the cases and the investigation was complemented by determining the
      vitamin B12 level, which proved nutritional Co/vitamin B12 deficiency, further
      verified by an increased MMA (methylmalonic acid) level in plasma. Deficiencies
      were found mainly in the Tobeatic and Cape Breton Highland regions. No
      indications of molybdenosis or other trace element disturbances were found in
      Nova Scotia. Otherwise, extremely high Cd levels (148 mg Cd/kg kidney wet wt.,
      maximum) were found, though probably not contributing to the moose sickness. The
      Cd burden of moose on mainland Nova Scotia was more than 50% higher than that of
      moose in Huntville and Alonquin (Ontario, Canada) and five- to six-fold is higher
      than the highest Cd levels found in Sweden. To counteract the bio-geochemical
      effects of Co deficiency in the moose environment, provision of Co-containing
      salt licks is suggested.

PMID- 14654278
TI  - Seasonal changes in the sensitivity of river microalgae to atrazine and
      isoproturon along a contamination gradient.
AB  - A study was undertaken to investigate the environmental impact of herbicides on
      natural communities of freshwater periphyton and phytoplankton in the river
      Ozanne and in related nearby water reservoirs, including both pristine and
      pesticide- (atrazine and isoproturon) contaminated stations. The microalgal
      toxicity of both herbicides was investigated by short-term studies, using the in
      vivo fluorescence pattern to perform dose-effect experiments. The taxonomic
      composition of the communities sampled was assessed by microscopy and by HPLC
      pigment analysis. The EC50 (periphyton) or EC125 (phytoplankton) values,
      calculated using in vivo fluorescence endpoints, increased with the herbicide
      concentration found in the water. In contrast, the structure of the algal
      communities (periphyton) inhabiting the contaminated stations seemed to be
      permanently affected when compared to the reference community. A 'memory effect'
      could be detected, both in herbicide sensitivity and in the structure of
      periphytic communities that persisted even when peak contaminations had
      disappeared. This study shows that the response of algal communities is likely to
      reflect past selection pressures, and suggests that the function and structure of
      a community could both be modified by the persistent or repeated presence of
      microcontaminants in natural environments. We could use short-term
      ecotoxicological tests on freshwater microalgae to assess the effects of past
      temporary contaminations by agricultural pesticides, and combining this with
      diversity indices could make it possible to assess the ecotoxicological risk of
      herbicide contamination even when a complete chemical analysis of the
      contamination is not feasible.

PMID- 14654279
TI  - The effect of size on trace metal levels in raft cultivated mussels (Mytilus
      galloprovincialis).
AB  - Mussels are farmed in the coastal inlets of Galicia by means of floating raft
      culture. The growth of these bivalves is due to their great capacity to filter
      the water column, which unfortunately, also exposes them to dangerous
      contaminants, including heavy metals. Thus, it is imperative that mussels be
      monitored for metals. Size has sometimes been shown to be an important variable,
      but contradictory results have been found. In order to monitor metals in raft
      mussels, it is necessary to compile information regarding the number of size
      classes according to shell length, which must be taken into account to obtain a
      representative sampling, as well as the number of sample replicates that must be
      included. Also, to be considered is the cost incurred by carrying out the
      collection, preparation and analysis per sample. The purpose of this study is to
      provide information about the effect of size, indicated by shell length on the
      metal content of raft mussels. The ability of 10 mussel-pooled samples to
      discriminate real differences in metal concentration was also studied. In
      general, a positive relationship between metal content and shell length was
      observed; a similar relation was found between the weight of soft tissues and
      shell length. As expected from the similarity encountered between relationships
      of metal content and dry weight-length, the concentrations of the different
      metals in the soft tissues would not seem to depend on the shell length. Metal
      concentrations, in this study, were found to be approximately 45 ppm of Hg, 0.5
      ppm of Cd, 0.7 ppm of Pb, 0.5 ppm of Cr, 0.6 ppm of Ni, 8 ppm of As, 5 ppm of Cu
      and 122 ppm of Zn; on a dry weight basis. No significant differences between
      metal concentrations at different shell lengths were detected. Another important
      observation was the high variability observed within one size, indicating poor
      homogeneity in subgroups of similar size, which must be minimized if the number
      of samples is not enhanced as indicated by power and size analysis.

PMID- 14654280
TI  - A comparison of organic contaminants in two high Arctic lake ecosystems, Bjornoya
      (Bear Island), Norway.
AB  - Lake Ellasjoen and Lake Oyangen are two high Arctic lake ecosystem located on the
      island Bjornoya (74 degrees 30' N, 19 degrees 00' E) in the Barents Sea. High
      levels of persistent organic pollutants (POPs), especially PCB and p,p'-DDE, were
      found in sediment and biota from Lake Ellasjoen while levels were several times
      lower in Lake Oyangen. Stable isotope signatures (delta15N) in comparable
      organisms (e.g. zooplankton, Arctic char) collected from both the lakes were also
      significantly different. The values of delta15N were 6-10 per thousand higher in
      the organisms from Ellasjoen than from Oyangen. In both Ellasjoen and Oyangen, a
      statistically significant correlation (P<0.05) was found between the levels of
      PCB and DDT, and delta15N values in organisms indicating enhanced bioaccumulation
      for higher trophical level lake organisms. As the lakes on Bjornoya are remote,
      more than 500 km from any known point source, the presence of POPs is most likely
      the result of long-range transport of contaminants to the area. The observed
      higher contaminant concentrations associated with the Ellasjoen ecosystem is
      attributed to two factors. Ellasjoen is located in the southern, mountainous part
      of Bjornoya and it is likely that this area receives more precipitation, and
      thereby more airborne contaminants, than the flatter areas further north on the
      island (i.e. the area around Oyangen). In addition, higher delta15N-levels in
      organisms from Ellasjoen as compared to Oyangen indicate the input of guano from
      seabirds using the lake as a resting area as an additional source of POPs to
      Ellasjoen.

PMID- 14654281
TI  - Vertical distribution of Th-isotope ratios, 210Pb, 226Ra and 137Cs in sediment
      cores from an estuary affected by anthropogenic releases.
AB  - In an estuary system highly polluted by mining and industrial activities, the
      sections of sediment cores affected by anthropogenic inputs of U-series
      radionuclides (due to fertilizer plants releases) were determined through the
      vertical profiles of Th-isotopic ratio (230Th/232Th). Also, when possible, a
      modified version of the 210Pb dating method was applied in the uncontaminated
      sections of these cores. Using the information provided by the Th-isotopic ratio
      and 210Pb methods, we were able to establish confident chronologies, covering the
      last century, in several of the analysed sediment cores. These chronologies will
      be used in forthcoming research to study the time evolution of pollutant
      concentrations in the estuary. Additionally, and based on the established
      chronologies, we have found that sedimentation rates have drastically increased
      in some zones of the estuary since the commencement of several industrial
      activities in the surrounding environment and since the construction of two dikes
      in the area.

PMID- 14654282
TI  - An estimation of the spatial distribution of agricultural ammonia emissions in
      the Greater Athens Area.
AB  - An assessment of the magnitude and the spatial distribution of ammonia emissions
      originating from agricultural practices in the Greater Athens Area (GAA) is
      performed due to the primary role of ammonia in aerosol formation. As no emission
      factors are available for the area of interest, the emissions were estimated
      using typical emission factors for the emissions from animals, fertilized and
      unfertilized cultures, as well as the 1996 primary statistical data of the
      agricultural census for the GAA. Our analysis estimated the annual ammonia
      emissions from agricultural sources to be approximately 13,250+/-40% t of ammonia
      per year. This detailed ammonia emission record can and will be used for the
      study, via modeling, of the serious aerosol problem in the GAA.

PMID- 14654283
TI  - Atmospheric heavy metal deposition in Finland during 1985-2000 using mosses as
      bioindicators.
AB  - Heavy metal deposition and changes in the deposition patterns were investigated
      on the basis of surveys carried out in 1985, 1990, 1995 and 2000. The
      concentrations of 10 elements (Cd, Cr, Cu, Fe, Ni, Pb, Zn and V; and As and Hg
      since 1995) were determined on moss (Hylocomium splendens, Pleurozium schreberi)
      samples collected from the same permanent sample plots in each survey. The heavy
      metal concentrations, apart from those in southernmost Finland and close to a
      number of major emission sources, were relatively low. The mean concentrations of
      all the heavy metals decreased during the period covered by the surveys. The
      metals that showed the strongest decrease in concentration since 1985 were Pb
      (78%), V (70%) and Cd (67%). The concentrations of the other heavy metals
      decreased by 16-34%. The concentrations of Cr, Cu and Ni were clearly associated
      with local emission point sources and changes in emission levels. The
      concentrations of As and Hg, which were measured for the first time during the
      1995 survey, decreased on the average by 26% and 10%, respectively.

PMID- 14654284
TI  - Upward mobilization of 137Cs in surface soils of Chamaecyparis obtusa Sieb. et
      Zucc. (hinoki) plantation in Japan.
AB  - The use of 137Cs has recently been adopted to estimate erosion in hinoki
      plantations in Japan. However, there have been several reports of the upward
      mobilization of 137Cs in forest humus layers. In this study, the vertical
      distribution of 137Cs within the soil profile was measured in a hinoki
      plantation. In order to confirm the upward migration of 137Cs from mineral soil
      to fresh surface litter and to identify mechanisms of the transfer, changes in
      137Cs specific activity in the contents of litterbags were examined in a hinoki
      plantation. A controlled laboratory experiment was also conducted to assess the
      effect of microbial activity on the upward migration of 137Cs. As a result, the
      higher 137Cs activities in the surface organic layer of a hinoki plantation than
      in fresh litter and the increasing 137Cs total content of litterbags with time
      demonstrated the upward mobilization of 137Cs from mineral soil to the surface
      organic layer. Physical movement of soil particles by raindrop splash was
      considered an important process in 137Cs upward migration. The results of our
      laboratory experiment indicate an influence from soil microbial activity on the
      upward mobilization of 137Cs. Thus, upward migration of 137Cs and constant litter
      removal by runoff may induce 137Cs loss from steep forested catchments and
      underestimation of the 137Cs inventory leading to the overestimation of soil
      redistribution rates.

PMID- 14654285
TI  - Plutonium isotopes in seas around the Korean Peninsula.
AB  - 239+240Pu concentrations and 240Pu/239Pu atom ratios in coastal seas adjacent to
      the Korean Peninsula were determined, during the period 1999 to 2002, to assess
      the current distribution and to identify sources of Pu isotopes. 239+240Pu
      concentrations in surface waters ranged from 3.1 to 22.3 mBq m(-3) with higher
      concentrations in winter than in summer. 239+240Pu concentrations in seawaters
      around the Korean Peninsula are greater than that in the western North Pacific.
      240Pu/239Pu atom ratios ranged from 0.18 to 0.33 with an average value of 0.25+/
      0.03, which is significantly higher than the global fallout average. The
      240Pu/239Pu atom ratios of the 2000 m deep entire water column in the south
      western part of the East Sea (Sea of Japan) was comparable to that observed in
      waters near Bikini Atoll. The higher 240Pu/239Pu atom ratios than that of global
      fallout may be explained by the hypothesis that the earlier input signal of low
      240Pu/239Pu atom ratio (0.18-0.19) of global fallout plutonium in seas adjacent
      to the Korean Peninsula is being gradually diluted by the high 240Pu/239Pu atom
      ratio plutonium transported from the tropical Pacific Proving Grounds via
      prevailing ocean current.

PMID- 14654286
TI  - Importance of the biogenic organic matter in photo-formation of dissolved gaseous
      mercury in a culture of the marine diatom Chaetoceros sp.
AB  - Laboratory experiments on DGM production under light/dark cycles in a culture of
      the marine diatom Chaetoceros sp. spiked with 200 ng l(-1) of mercury have been
      performed. DGM formation has been investigated also in the cell exudates,
      obtained by filtration of the cell culture. Results show that the cell culture
      and the filtrate give the same value of DGM production (2.24+/-0.88 pg min(-1) l(
      1) and 2.23+/-0.02 pg min(-1) l(-1), respectively) in the light (40 W m(-2)),
      values much higher than to those obtained in the medium culture alone. A
      significant DGM production has been measured in dark conditions both in the cell
      culture (0.48+/-0.11 pg min(-1) l(-1)) and in the filtrate (0.85+/-0.10 pg min(
      1) l(-1)). The results highlight that the organic compounds released by the cell
      in the culture medium play a fundamental role in the DGM photo-formation
      processes.

PMID- 14654287
TI  - Environmental concerns related to high thallium levels in soils and thallium
      uptake by plants in southwest Guizhou, China.
AB  - Thallium (Tl) contamination in soils poses a significant threat to human health
      due to the high toxicity of Tl and its ready assimilation by crops. This study is
      focused on high concentrations of Tl in soils in the Lanmuchang area of southwest
      Guizhou, China, which is related to natural processes of Tl-rich sulfide
      mineralization. Thallium contents range from 40 to 124 mg/kg in soils originating
      from the mining area, from 20 to 28 mg/kg in slope wash materials, from 14 to 62
      mg/kg in alluvial deposits downstream, from 1.5 to 6.9 mg/kg in undisturbed
      natural soils and <0.2 to 0.5 mg/kg Tl in soils from the background area. These
      values indicate that both the erosion of natural soils from the Tl mineralized
      area and the mining activity are responsible for the distribution of high Tl
      concentrations in soils. Two other important toxic metals of interest, mercury
      and arsenic, also show high contents in soils, and are generally higher than Tl
      concentrations. Thallium concentration in plants exhibit species-dependent
      preferences. Thus, the enrichment of Tl in the edible parts of crop species
      decreases in the following order: green cabbage>carrot>chili>Chinese
      cabbage>rice>corn. The highest level of Tl in green cabbage is up to 500 mg/kg as
      dry wt., surpassing the values of Tl in the soils in which the green cabbages
      grow. In contrast, Hg and As are relatively less concentrated in local plants.
      The average daily uptake of Tl by the villagers of the Lanmuchang area through
      consumption of locally planted crops has been estimated to be 1.9 mg/person,
      which is 50 times the daily ingestion of individuals from the Tl-free background
      area. The daily ingestion of As and Hg from the study area are 0.03 and 0.01 mg,
      respectively. This indicates that Tl in the contaminated soils related to the
      natural Tl mineralization is being readily transferred to the human body through
      the food chain, and poses a significant threat to the health of the local
      villagers. Arsenic may pose a lesser health hazard, but mercury has an
      insignificant health risk. This study illustrates a real environmental concern
      related to land use and human health in areas containing high contents of Tl in
      soils associated with the natural occurrence of Tl-rich sulfides and coals, with
      or without mining activities. Thallium contamination in soils should be a
      critical parameter for proper land use and health related environmental planning
      and regulations.

PMID- 14654288
TI  - Precipitation scavenging of polycyclic aromatic hydrocarbons in Mumbai, India.
AB  - The concurrent rain and air sampling was conducted for thirteen rain events
      between the last week of May and end of June 2001. Concentration of total PAHs
      varied from 84.25 to 777.49 ng/l whereas that in air was in the range of 4.05 to
      34.42 ng/m(3). In rainwater the lower molecular weight PAHs (e.g. Phenanthrene,
      Fluoranthene and Pyrene) were found to be more prominent than the higher
      molecular weight compounds. The gas phase scavenging ratio (Wg) was found to
      increase with the molecular weight of the compound. The particle phase scavenging
      ratio (Wp) values for the more volatile PAHs were generally much higher than
      those for less volatile PAHs. The higher MW PAHs have Wg values equal to or
      larger than their Wp values.

PMID- 14654290
TI  - Genes responsible for anaerobic fumarate and arginine metabolism are involved in
      growth suppression in Salmonella enterica serovar Typhimurium in vitro, without
      influencing colonisation inhibition in the chicken in vivo.
AB  - From a collection of over 2800 Salmonella enterica subspecies Enterica serotype
      Typhimurium F98 Tn5-TC1 insertion mutants 14 were identified as expressing growth
      non-suppressive phenotype under strict anaerobic conditions. Sequence analysis of
      regions flanking the Tn insertions revealed that most of the selected mutants
      were defective in genes contributing to the anaerobic fumarate uptake and
      generation (insertions in dcuA, dcuB and aspA), or to the anaerobic L-arginine
      utilisation pathway (insertions in STM4467 encoding a putative arginine
      deiminase, and in between speF encoding ornithine decarboxylase and kdpE coding a
      response regulator protein). Mutants defective in flagellum synthesis (flhA) were
      also identified. In contrast to the in vitro results, all the mutants colonised 1
      day-old chicks efficiently and suppressed the super-infection of chicks by the
      parent strain. This clearly indicates that neither of the metabolic pathways
      mentioned above nor motility play essential roles in lower intestinal tract
      colonisation.

PMID- 14654289
TI  - Evaluation of virulence of Mycoplasma hyopneumoniae field isolates.
AB  - The course of enzootic pneumonia, caused by Mycoplasma hyopneumoniae, is strongly
      influenced by management and housing conditions. Other factors, including
      differences in virulence between M. hyopneumoniae strains, may also be involved.
      The aim of this study was to evaluate the virulence of six M. hyopneumoniae field
      isolates and link it to genetic differences as determined by randomly amplified
      polymorphic DNA (RAPD) analysis. Ninety, conventional M. hyopneumoniae-free
      piglets were inoculated intratracheally with the field isolates, a virulent
      reference strain or sterile culture medium. Animals were examined daily for the
      presence of disease signs and a respiratory disease score (RDS) was assessed per
      pig. Twenty-eight days post infection, pigs were euthanized, blood sampled and a
      lung lesion score was given. Lung samples were processed for histopathology,
      immunofluorescence testing for M. hyopneumoniae and isolation of M.
      hyopneumoniae. RAPD analysis was performed on all M. hyopneumoniae strains.
      Significant differences between isolates were found for the RDS, lung lesion
      score, histopathology, immunofluorescence and serology. Based on the results of
      the different parameters, isolates were divided into three "virulence" groups:
      low, moderately and highly virulent strains. Typically, a 5000 bp RAPD fragment
      was associated with the highly and moderately virulent strains whereas it was
      absent in low virulent strains. It was concluded that high variation in virulence
      exists between M. hyopneumoniae strains isolated from different swine herds.
      Further studies are required to determine whether the 5000 bp fragment obtained
      in the RAPD analysis can be used as a virulence marker.

PMID- 14654291
TI  - Recovery of Salmonella enterica from seropositive finishing pig herds.
AB  - The aim of this study was to assess the probability of detecting Salmonella from
      pen faecal samples in seropositive classified finishing pig herds. The study
      involved 77 herds from Denmark (20), The Netherlands (20), Greece (17) and
      Germany (20). The serological herd status was determined by the blood-sampling of
      50 finishing pigs. Bacteriological sampling was performed by 20 pen faecal
      samples per herd. Over-all, 47% of the blood samples had an OD% larger than 10
      and 23% larger than 40. Salmonella was isolated from 135 (9.3%) pen faecal
      samples in 32 herds (42%). Twenty-eight of these herds (87.5%) had a within-herd
      seroprevalence larger than 50% at sample cut-off OD% > 10. In our study, there
      was an increasing probability of recovering Salmonella with increasing within
      herd seroprevalence. However, this was only a moderate correlation. A correlation
      coefficient of 0.62 was found between the proportion of culture positive- and
      seropositive samples in a herd at cut-off OD%> 10 and of 0.58 at cut-off OD% >
      40. Serology is a measure of historical exposure, which may or may not correlate
      closely to the microbiological burden at the time of sampling. Due to the low
      sensitivity of culture methods, apparent 'false-positive' serological results may
      well represent real infections not detected by bacteriological testing. For
      screening purposes, serological testing provides an indication of exposure to
      Salmonella, which forms the basis for targeted sampling, intervention and
      logistic slaughter procedures.

PMID- 14654292
TI  - Capsule thickness and amounts of a 39 kDa capsular protein of avian Pasteurella
      multocida type A strains correlate with their pathogenicity for chickens.
AB  - Capsule thickness of avian Pasteurella multocida type A strains was determined by
      transmission electron microscopy after labeling with polycationic ferritin and
      compared with their pathogenicity for chickens. The capsule thickness of P.
      multocida strains Pm-18 and X-73 was 81.4 and 50.1 nm on average, respectively.
      These strains were highly virulent for chicken, whereas the less virulent strains
      Pm-1 and Pm-3 had a thin and irregular capsule, 21.0 and 29.8 nm on average,
      respectively. However, the thickest capsule was observed in strain P-1059, 101.2
      nm on average, and the strain revealed moderate virulence. The noncapsulated
      variant P-1059B, which was derived from strain P-1059, revealed low virulence.
      The six P. multocida strains were examined with regard to protein content on the
      capsule of organisms. Amounts of total proteins of crude capsular extract (CCE)
      from capsulated strains were approximately twice those of the noncapsulated
      strains. The amount of an antigenic 39 kDa protein in the CCE were found to
      correlate with the capsule thickness, since heavily capsulated strains exhibited
      the greatest amount, whereas noncapsulated strains including noncapsulated and
      low virulent variant P-1059B possessed little 39 kDa protein. The results
      demonstrated that the capsule thickness and the quantity of a 39 kDa capsular
      protein of avian P. multocida type A strains correlated with their pathogenicity
      for chickens.

PMID- 14654293
TI  - A 39 kDa protein mediates adhesion of avian Pasteurella multocida to chicken
      embryo fibroblast cells.
AB  - To clarify the role of avian Pasteurella multocida capsule in pathogenesis,
      adhesion of capsulated strains P-1059, X-73 and Pm-18, and noncapsulated strains
      P-1059B, Pm-1 and Pm-3 to chicken embryo fibroblast (CEF) cells was compared.
      Number of adherent organisms of the capsulated strains to CEF cells were
      approximately three times as much as noncapsulated strains indicating that
      adhesive properties were enhanced by the presence of bacterial capsule.
      Pretreatments of the bacterial cells with heat, trypsin, or with antiserum caused
      a marked decrease in adhesion of capsulated strain P-1059 and its noncapsulated
      variant P-1059B. However, depolymerization of capsular hyaluronic acid with high
      dose of hyaluronidase enhanced adhesion of these strains. Combined treatments of
      the bacterial cells with both hyaluronidase and trypsin significantly (P < 0.05)
      inhibited the adherence of strain P-1059 as compared to the treatment only with
      trypsin, but strain P-1059B was not affected. SDS-PAGE profiles of crude capsular
      extract (CCE) prepared from capsulated strain P-1059 and its noncapsulated
      variant P-1059B grown on dextrose starch agar (DSA) plates by heating at 56
      degrees C in a 2.5% NaCl solution demonstrated eight protein bands of 28, 34, 36,
      39, 52, 56, 63 and 93 kDa. The 28, 34 and 36 kDa proteins were commonly major for
      both strains, and the 39 kDa protein was major only for strain P-1059 but poor in
      strain P-1059B. Outer membrane protein (OMP) profiles were identical with a major
      protein at 34 kDa and four minor proteins between the two strains. The adhesion
      of strain P-1059 and strain P-1059B to CEF cells was inhibited significantly (P <
      0.01) by treatment with rabbit antisera against P-1059, P-1059B, CCE or 39 kDa
      protein of strain P-1059 as compared to the treatment with either PBS or with
      normal rabbit serum. These results indicated that an antigenic 39 kDa protein in
      the capsule may be responsible for adhesion of avian P. multocida type A strains
      to CEF cells as a virulence factor.

PMID- 14654294
TI  - Predominance of the papGII allele with high sequence homology to that of human
      isolates among avian pathogenic Escherichia coli (APEC).
AB  - Avian pathogenic Escherichia coli (APEC) are often found in poultry and are
      responsible for a set of diseases, commonly referred to as avian colibacillosis.
      One of the important virulence factors is adhesion to different epithelial
      surfaces, which is mediated by pili. P pili are thought to play a role by means
      of their PapG adhesin, which occurs in three molecular variants: PapGI, PapGII
      and PapGIII. This study is the first to determine and analyse the distribution of
      the different papG alleles in APEC. Our results show a significant predominance
      of the papGII allele above all other alleles or allele combinations. No
      statistically significant associations could be found between papG allele
      distribution and the type of bird, organ of isolation and O serogroup. Finally,
      the papGII and papGIII sequences showed high homology with mammalian (including
      human) source papG sequences.

PMID- 14654295
TI  - Persistence of viral RNA segments in the central nervous system of mice after
      recovery from acute influenza A virus infection.
AB  - One-hundred thirty-seven BALB/c mice were intranasally inoculated with
      neurotropic avian influenza A virus (H5N3). Thirty-nine of these mice died within
      16 days post-inoculation (PID) and 98 of the mice recovered from the infection.
      To investigate whether viral antigens and genomes persist in the central nervous
      system (CNS) of recovered mice, immunohistochemistry and reverse transcription
      polymerase chain reaction (RT-PCR) methods were performed. Histopathologically,
      mild interstitial pneumonia and non-suppurative encephalomyelitis restricted to
      the basal part of the frontal lobe of the cerebrum, brain stem and thoracic
      spinal cord were observed in BALB/c mice until 40 PID. Small amounts of viral
      antigens were detected in the brain and spinal cord and some viral RNA segments
      (NA, NP, M, PA, HA, NS, PB1) were intermittently detected in the CNS until 48
      PID. Immunosuppression of these mice by dexamethazone (DEX) treatment did not
      increase the frequency of detection of the lesions, viral antigens or genomes.
      These findings suggest that viral genomes of neurovirulent influenza virus
      persist with restricted transcriptive activity in the CNS of the mice even after
      clinical recovery from the infection.

PMID- 14654296
TI  - The attenuated sopB mutant of Salmonella enterica serovar Typhimurium has the
      same tissue distribution and host chemokine response as the wild type in bovine
      Peyer's patches.
AB  - Salmonella enterica serovar Typhimurium is an important cause of enteric
      infections in farm animals and it is one of the most frequent food borne
      infections worldwide. Serovar Typhimurium lacking the sopB gene is attenuated for
      induction of host inflammatory response and fluid accumulation into the
      intestinal lumen, which correlates with clinical diarrhea. SopB is an inositol
      phosphate phosphatase, but its exact role in the pathogenesis of salmonellosis is
      still unclear. We employed the bovine ileal ligated loop model to compare the
      tissue distribution of a sopB mutant and its wild type parent serovar
      Typhimurium. Sections of the Peyer's patches were histologically processed and
      immuno-stained for detection of serovar Typhimurium. In addition, samples were
      processed for transmission electron microscopy, and the profile of expression of
      host chemokine and cytokine responses was assessed. Ultrastructurally both
      strains had the same ability to invade intestinal epithelial cells. No
      differences were detected in the tissue distribution of the sopB mutant and the
      wild type organism and both strains elicited the same profile of chemokines and
      pro-inflammatory cytokines. In conclusion, our results indicate that the
      attenuation of the sopB mutant is associated with pathogenic mechanisms other
      than invasion and distribution in host intestinal tissues.

PMID- 14654297
TI  - Hydrogen sulfide: from the smell of the past to the mediator of the future?
AB  - Gases such as nitric oxide and carbon monoxide play important roles both in
      normal physiology and in disease. In recent years, interest has been directed
      towards other naturally occurring gases, notably hydrogen sulfide (H(2)S), which
      is both a potent vasodilator and a mediator of long-term potentiation in the
      brain. This article focuses on recent work that suggests a role for H(2)S, and
      perhaps other gases, in the CNS and cardiovascular system.

PMID- 14654298
TI  - A site-specific polymeric drug carrier for renal disease treatment.
AB  - A well-designed polymeric carrier for site-specific drug delivery in the
      treatment of renal disease has been reported recently. Approximately 80% of the
      water-soluble polymer poly(vinylpyrrolidone-co-dimethyl maleic anhydride
      selectively accumulated in the kidney of mice 24 h after intravenous injection.
      The detailed mechanism of such selective accumulation is not clear but an energy
      dependent process, other than endocytosis, might be involved in the uptake of the
      polymer. This study is the first to report active targeting using a synthetic
      polymeric drug carrier.

PMID- 14654299
TI  - Interleukin 4 treatment of psoriasis: are pleiotropic cytokines suitable
      therapies for autoimmune diseases?
AB  - Many human autoimmune diseases are still treated by a combination of
      corticosteroids and general immunosuppression. A better understanding of the
      pathogenesis of these diseases has led to therapies that are more specific than
      current therapies of some of these disorders. In psoriasis, T helper (Th) cells
      with a pro-inflammatory phenotype (Th1) are considered essential to the disease
      process. A recent clinical trial of interleukin 4 in psoriasis has demonstrated
      that such pleiotropic cytokines can be used safely and effectively to correct
      imbalances in immune function.

PMID- 14654300
TI  - Sparing animals and progressing in science.

PMID- 14654301
TI  - Fundamental molecular mechanism of the CNS effects of TRH.

PMID- 14654302
TI  - Assessing predictors of drug-induced torsade de pointes.
AB  - Torsades de pointes (TdP) is a malignant polymorphic ventricular tachyarrhythmia
      that can be caused by drugs that induce electrophysiological changes. Although
      the number of drugs known to cause TdP has increased in recent years, there is no
      cell-based assay, in vitro heart preparation or animal model that predicts the
      potential of a drug to induce TdP in humans. Nevertheless, certain
      electrophysiological events are known to be associated with the development of
      TdP. For example, a drug that prolongs action potential duration, induces early
      afterdepolarizations and ectopic beats, and increases dispersion of ventricular
      repolarization is likely to cause TdP. By contrast, a drug that does not induce
      these changes is unlikely to cause TdP. The exact relationship between these
      electrophysiological events and the development of TdP has not been defined, but
      the potential of a drug to elicit these events might predict its pro-arrhythmic
      risk.

PMID- 14654303
TI  - Non-visual GRKs: are we seeing the whole picture?
AB  - G-protein-coupled receptor kinases (GRKs) comprise a family of seven mammalian
      serine/threonine protein kinases that phosphorylate and regulate agonist-occupied
      or constitutively active G-protein-coupled receptors (GPCRs). Studies of the
      details and consequences of these mechanisms have focused heavily on the original
      beta-adrenoceptor kinase (beta-ARK) family (GRK2 and GRK3) and, in particular, on
      phosphorylation-dependent recruitment of adaptor proteins such as the beta
      arrestins. However, recent work has indicated roles for the other, non-visual
      GRKs (GRK4, GRK5 and GRK6) and has revealed potential phosphorylation-independent
      regulation of GPCRs by GRK2 and GRK3. In this article, we review this newer
      information and attempt to put it into context with GRKs as physiological
      regulators that could be appropriate targets for future pharmacological
      intervention.

PMID- 14654304
TI  - Opioid hyperalgesia and tolerance versus 5-HT1A receptor-mediated inverse
      tolerance.
AB  - In addition to analgesia, opioids also produce paradoxical hyperalgesic effects
      following acute and chronic treatment. In this article, we review the occurrence
      of this hyperalgesia under several conditions, and discuss the potential
      mechanisms and clinical implications. We also review recent evidence that
      paradoxical analgesia and inverse tolerance induced by stimulation of 5-HT(1A)
      receptors, which is a mirror image of opioid-induced hyperalgesia and tolerance,
      might achieve clinically significant analgesia in chronic pain.

PMID- 14654305
TI  - Leukocyte and endothelial cell adhesion molecules as targets for therapeutic
      interventions in inflammatory disease.
AB  - Inflammation is a fundamental response to tissue injury and invasion of
      pathogens, but it is detrimental in clinically important inflammatory disorders.
      Leukocytes are key players in the inflammatory response because of their
      antimicrobial, secretory and phagocytic activities. They are recruited to the
      inflamed tissue by sequential adhesive interactions between leukocytes and the
      endothelium that are mediated by cell-adhesion molecules (CAMs) on the surface of
      the interacting cells. The effects of many anti-inflammatory drugs can be
      ascribed, in part, to inhibition of the expression of CAMs. However, in the
      search for more selective and potent drugs for clinically important diseases such
      as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease,
      allergies and atherosclerosis, direct inhibition of the function of CAMs has
      attracted increasing interest. In recent years, the development of synthetic
      antagonists has provided better opportunities for drug targeting. Future advances
      in this field hold new prospects for therapeutic intervention in human
      inflammatory disorders.

PMID- 14654306
TI  - Fatty acid-sensitive two-pore domain K+ channels.
AB  - K(+) channels that are activated by free fatty acids (here called K(FA) channels)
      are found throughout the CNS and in some peripheral tissues. In addition to free
      fatty acids, membrane stretch (cell swelling), changes in intracellular pH and
      volatile anaesthetic agents also activate K(FA) channels. Neurotransmitters that
      bind to G(s)-protein-coupled receptors inhibit K(FA) current via cAMP-mediated
      phosphorylation. K(FA) channels are native members of the TREK-TRAAK family,
      which belongs to the tandem-pore class of K(+) (K(2P)) channels. The unique
      properties of K(FA) channels indicate that they are well suited to sensing
      various types of stress that occur in the cell.

PMID- 14654307
TI  - Techniques: plasmon-waveguide resonance (PWR) spectroscopy as a tool to study
      ligand-GPCR interactions.
AB  - Plasmon-waveguide resonance (PWR) spectroscopy can be applied to integral
      membrane proteins incorporated into a supported lipid bilayer without the need
      for labeling. With high sensitivity and wide dynamic range, this technique can be
      used to characterize the kinetics and thermodynamics of conformational events
      associated with the binding of ligands to G-protein-coupled receptors (GPCRs),
      and to directly examine the interactions of GPCRs with G proteins and other
      downstream effectors in signal transduction. This allows an easy distinction to
      be made between agonists, antagonists and inverse agonists, and provides a
      powerful new tool for studying membrane signaling and for drug development.

PMID- 14654308
TI  - The untapped potential of palliative care for AIDS.

PMID- 14654309
TI  - Unexplained antepartum stillbirth in pregnancies after a caesarean delivery.

PMID- 14654310
TI  - Climate change will increase demands on malaria control in Africa.

PMID- 14654311
TI  - Lathyrism: aqueous leaching reduces grass-pea neurotoxicity.

PMID- 14654312
TI  - The rudimentary phase of personalised medicine: coronary risk scores.

PMID- 14654313
TI  - Hormones and insulin resistance during pregnancy.

PMID- 14654315
TI  - Caesarean section and risk of unexplained stillbirth in subsequent pregnancy.
AB  - BACKGROUND: Caesarean section is associated with an increased risk of disorders
      of placentation in subsequent pregnancies, but effects on the rate of antepartum
      stillbirth are unknown. We aimed to establish whether previous caesarean delivery
      is associated with an increased risk of antepartum stillbirth. METHODS: We linked
      pregnancy discharge data from the Scottish Morbidity Record (1980-98) and the
      Scottish Stillbirth and Infant Death Enquiry (1985-98). We estimated the relative
      risk of antepartum stillbirth in second pregnancies using time-to-event analyses.
      FINDINGS: For 120633 singleton second births, there were 68 antepartum
      stillbirths in 17754 women previously delivered by caesarean section (2.39 per
      10000 women per week) and 244 in 102879 women previously delivered vaginally
      (1.44; p<0.001). Risk of unexplained stillbirth associated with previous
      caesarean delivery differed significantly with gestational age (p=0.04); the
      excess risk was apparent from 34 weeks (hazard ratio 2.23 [95% CI 1.48-3.36]).
      Risk was not attenuated by adjustment for maternal characteristics or outcome of
      the first pregnancy (2.74 [1.74-4.30]). The absolute risk of unexplained
      stillbirth at or after 39 weeks' gestation was 1.1 per 1000 women who had had a
      previous caesarean section and 0.5 per 1000 in those who had not. The difference
      was due mostly to an excess of unexplained stillbirths among women previously
      delivered by caesarean section. INTERPRETATION: Delivery by caesarean section in
      the first pregnancy could increase the risk of unexplained stillbirth in the
      second. In women with one previous caesarean delivery, the risk of unexplained
      antepartum stillbirth at or after 39 weeks' gestation is about double the risk of
      stillbirth or neonatal death from intrapartum uterine rupture.

PMID- 14654316
TI  - Effect of ultraviolet germicidal lights installed in office ventilation systems
      on workers' health and wellbeing: double-blind multiple crossover trial.
AB  - BACKGROUND: Workers in modern office buildings frequently have unexplained work
      related symptoms or combinations of symptoms. We assessed whether ultraviolet
      germicidal irradiation (UVGI) of drip pans and cooling coils within ventilation
      systems of office buildings would reduce microbial contamination, and thus
      occupants' work-related symptoms. METHODS: We undertook a double blind, multiple
      crossover trial of 771 participants. In office buildings in Montreal, Canada,
      UVGI was alternately off for 12 weeks, then turned on for 4 weeks. We did this
      three times with UVGI on and three times with it off, for 48 consecutive weeks.
      Primary outcomes of self-reported work-related symptoms, and secondary outcomes
      of endotoxin and viable microbial concentrations in air and on surfaces, and
      other environmental covariates were measured six times. FINDINGS: Operation of
      UVGI resulted in 99% (95% CI 67-100) reduction of microbial and endotoxin
      concentrations on irradiated surfaces within the ventilation systems. 771
      participants appeared to remain masked, and reported no adverse effects. On the
      basis of within-person estimates, use of UVGI was associated with significantly
      fewer work-related symptoms overall (adjusted odds ratio 0.8 [95% CI 0.7-0.99]),
      as well as respiratory (0.6 [0.4-0.9]) and mucosal (0.7 [0.6-0.9]) symptoms than
      was non-use. Reduction of work-related mucosal symptoms was greatest among atopic
      workers (0.6 [0.5-0.8]), and never-smokers (0.7 [0.5-0.9]). With UVGI on, never
      smokers also had large reduction of work-related respiratory (0.4 [0.2-0.9]), and
      musculoskeletal symptoms (0.5 [0.3-0.9]). INTERPRETATION: Installation of UGVI in
      most North American offices could resolve work-related symptoms in about 4
      million employees, caused by microbial contamination of heating, ventilation, and
      air-conditioning systems. The cost of UVGI installation could in the long run
      prove cost-effective compared with the yearly losses from absence because of
      building-related illness.

PMID- 14654317
TI  - Potential effect of climate change on malaria transmission in Africa.
AB  - BACKGROUND: Climate change is likely to affect transmission of vector-borne
      diseases such as malaria. We quantitatively estimated current malaria exposure
      and assessed the potential effect of projected climate scenarios on malaria
      transmission. METHODS: We produced a spatiotemporally validated (against 3791
      parasite surveys) model of Plasmodium falciparum malaria transmission in Africa.
      Using different climate scenarios from the Hadley Centre global climate model
      (HAD CM3) climate experiments, we projected the potential effect of climate
      change on transmission patterns. FINDINGS: Our model showed sensitivity and
      specificity of 63% and 96%, respectively (within 1 month temporal accuracy), when
      compared with the parasite surveys. We estimate that on average there are 3.1
      billion person-months of exposure (445 million people exposed) in Africa per
      year. The projected scenarios would estimate a 5-7% potential increase (mainly
      altitudinal) in malaria distribution with surprisingly little increase in the
      latitudinal extents of the disease by 2100. Of the overall potential increase
      (although transmission will decrease in some countries) of 16-28% in person
      months of exposure (assuming a constant population), a large proportion will be
      seen in areas of existing transmission. INTERPRETATION: The effect of projected
      climate change indicates that a prolonged transmission season is as important as
      geographical expansion in correct assessment of the effect of changes in
      transmission patterns. Our model constitutes a valid baseline against which
      climate scenarios can be assessed and interventions planned.

PMID- 14654318
TI  - Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible
      nitric oxide synthase after death from septic shock.
AB  - BACKGROUND: Results of experimental and clinical studies have shown that septic
      shock is associated with cardiovascular autonomic failure. Thus, we aimed to
      investigate the existence of ischaemia and apoptosis within the cerebral
      autonomic centres that control the cardiovascular system in patients with septic
      shock. METHODS: In a prospective cohort study, we did post-mortem examinations of
      supraoptic and paraventricular nuclei, cerebral amygdala, locus coeruleus, and
      medullary autonomic nuclei in 19 patients with septic shock, seven with non
      septic shock and five who died suddenly from extracranial injury. Ischaemic and
      apoptotic neurons and microglial cells, and expression of tumour necrosis factor
      alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) were scored.
      FINDINGS: Ischaemic, neuronal, and microglial apoptosis scores differed between
      groups (p=0.0007, p<0.0001, and p=0.0037, respectively) and were higher in
      patients with septic shock than in those with non-septic shock (p=0.0033,
      p=0.0005, and p=0.0235, respectively), and extra-cranial injury related deaths
      (p=0.0027, p=0.0007, and p=0.0045, respectively). There was little microglial
      activation and glial expression of TNFalpha. The scores for endothelial iNOS
      expression were different between the three groups (p<0.0001), and were higher in
      septic shock than in non-septic shock (p=0.0009) and than in extracranial injury
      related deaths (p=0.0007). Vascular expression of iNOS also correlated (Spearman
      tau=0.57) with autonomic-centre neuronal apoptosis in the combined septic and non
      septic shock group. INTERPRETATION: Septic shock is associated with neuronal and
      glial apoptosis within the autonomic centres, which is strongly associated with
      endothelial iNOS expression.

PMID- 14654319
TI  - Fever and anuria.

PMID- 14654320
TI  - Genomic characterisation of the severe acute respiratory syndrome coronavirus of
      Amoy Gardens outbreak in Hong Kong.
AB  - Severe acute respiratory syndrome (SARS) is a global health concern. In Hong
      Kong, two major outbreaks, one hospital based and the other in the Amoy Gardens
      apartments, were identified. The frequency of diarrhoea, admission to intensive
      care, and mortality differed significantly between the two outbreaks. We did
      genomic sequencing for viral isolates from five Amoy Gardens patients. The virus
      sequence was identical in four of these five patients. The sequence data from one
      hospital case and the four identical community cases had only three nucleotide
      differences. Alterations in the SARS coronavirus genome are unlikely to have
      caused the distinctive clinical features of the Amoy Gardens patients, and these
      results highlight the importance of non-viral genomic factors in this outbreak.

PMID- 14654321
TI  - Food-aid cereals to reduce neurolathyrism related to grass-pea preparations
      during famine.
AB  - Neurolathyrism is a spastic paraparesis that can be caused by excessive
      consumption of the drought-resistant grass pea (Lathyrus sativus). Devastating
      neurolathyrism epidemics have occurred during major famine crises in various
      parts of the world. We investigated in a case-control study the effects of food
      aid on risk of paralysis. Risk increased with consumption of boiled grass pea
      (adjusted odds ratio 2.78, 95% CI 1.09-7.13 with cereals; 5.22, 2.01-13.55
      without cereal) and raw unripe green grass pea (1.96, 1.16-3.31; p=0.011), but
      not with the fermented pancake, unleavened bread, and gravy preparations. In a
      correlational study there was an inverse relation between the number of new cases
      and the amount of food-aid cereals distributed per person. During famine, cereals
      and nutritional information should reach people before they have grass pea as the
      only food.

PMID- 14654322
TI  - Hepatorenal syndrome.
AB  - Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis,
      characterised by renal failure and major disturbances in circulatory function.
      Renal failure is caused by intense vasoconstriction of the renal circulation. The
      syndrome is probably the final consequence of extreme underfilling of the
      arterial circulation secondary to arterial vasodilatation in the splanchnic
      vascular bed. As well as the renal circulation, most extrasplanchnic vascular
      beds are vasoconstricted. The diagnosis of HRS is currently based on the
      exclusion of other causes of renal failure. The prognosis is very poor,
      particularly when there is rapidly progressive renal failure (type 1). Liver
      transplantation is the best option in patients without contraindications to the
      procedure, but it is not always possible owing to the short survival expectancy.
      Therapies introduced during the past few years, such as vasoconstrictor drugs
      (vasopressin analogues, alpha-adrenergic agonists) or the transjugular
      intrahepatic portosystemic shunt, are effective in improving renal function.
      Nevertheless, liver transplantation should still be done in suitable patients
      even after improvement of renal function because the outcome of HRS is poor.
      Finally, recent findings suggest that the risk of developing HRS in the setting
      of spontaneous bacterial peritonitis may be reduced by the administration of
      albumin together with antibiotic therapy, and that of HRS occurring in severe
      alcoholic hepatitis can be lowered by administration of pentoxifylline. Although
      these findings need to be confirmed, these two strategies represent innovative
      approaches to lower the frequency of HRS in clinical practice.

PMID- 14654323
TI  - Glucocorticoids and invasive fungal infections.
AB  - Since the 1990s, opportunistic fungal infections have emerged as a substantial
      cause of morbidity and mortality in profoundly immunocompromised patients.
      Hypercortisolaemic patients, both those with endogenous Cushing's syndrome and,
      much more frequently, those receiving exogenous glucocorticoid therapy, are
      especially at risk of such infections. This vulnerability is attributed to the
      complex dysregulation of immunity caused by glucocorticoids. We critically review
      the spectrum and presentation of invasive fungal infections that arise in the
      setting of hypercortisolism, and the ways in which glucocorticoids contribute to
      their pathogenesis. A better knowledge of the interplay between glucocorticoid
      induced immunosuppression and invasive fungal infections should assist in earlier
      recognition and treatment of such infections. Efforts to decrease the intensity
      of glucocorticoid therapy should help to improve outcomes of opportunistic fungal
      infections.

PMID- 14654324
TI  - Perioperative management and monitoring in anaesthesia.
AB  - In recent years, several risk factors for adverse outcome in patients undergoing
      anaesthesia have been identified. Besides human errors, cardiovascular and
      respiratory complications are associated with substantial morbidity. Assessment
      of complications has promoted the introduction of basic physiological monitoring
      in clinical practice. Whether monitoring directly affects outcome is not proven;
      however, circumstantial evidence suggests that basic cardiorespiratory monitoring
      decreases the incidence of serious accidents. Prevention of hypothermia also
      reduces anaesthesia-related morbidity. Measurement of body temperature is
      mandatory, and active warming is a simple, effective technique to avoid
      hypothermia. Evidence is growing that patients with known or suspected coronary
      artery disease should be treated with beta blockers perioperatively. Whether the
      type of anaesthesia-ie, general or regional-is relevant to perioperative
      mortality remains unclear. In subgroups of patients at high risk, neuraxial
      anaesthesia reduces the rate of respiratory and cardiovascular complications.

PMID- 14654325
TI  - A serostatus-based approach to HIV/AIDS prevention and care in Africa.

PMID- 14654326
TI  - Nevirapine to prevent mother-to-child transmission of HIV-1 among women of
      unknown serostatus.

PMID- 14654327
TI  - The statin wars.

PMID- 14654328
TI  - The stain wars.

PMID- 14654329
TI  - The stain wars.

PMID- 14654330
TI  - The statin wars.

PMID- 14654331
TI  - The stain wars.

PMID- 14654332
TI  - The stain wars.

PMID- 14654334
TI  - Mercury pollution in India.

PMID- 14654335
TI  - Ethics of research involving vulnerable populations.

PMID- 14654337
TI  - Factors that precipitate development of diabetic foot ulcers in rural India.

PMID- 14654338
TI  - Effect of multidrug resistance on global tuberculosis control.

PMID- 14654339
TI  - Normative role for medical humanities.

PMID- 14654340
TI  - Prevalence of iodine deficiency worldwide.

PMID- 14654342
TI  - What's major about adverse cardiac events?

PMID- 14654343
TI  - A conspiracy against the professions.

PMID- 14654344
TI  - Allen Keller.

PMID- 14654346
TI  - Ecstasy.

PMID- 14654347
TI  - Let's waste our time!

PMID- 14654348
TI  - Adnan Al-Araji.

PMID- 14654349
TI  - Gene expression in early ischemic renal injury: clues towards pathogenesis,
      biomarker discovery, and novel therapeutics.
AB  - Acute renal failure (ARF) represents a common and serious problem in clinical
      medicine. Renal ischemia-reperfusion injury (IRI) is the major cause of ARF in
      the native and transplanted kidney. Several decades of research have provided
      successful therapeutic approaches in animal models, but translational efforts in
      humans have yielded disappointing results. The major reasons for this include a
      lack of early markers for ARF (and hence a delay in initiating therapy), and the
      multi-factorial nature of the disease. This review focuses on the use of cDNA
      microarrays to elucidate the molecular genetic mechanisms underlying tubule cell
      apoptosis, and to identify novel biomarkers for early renal IRI. Also presented
      is a comparative temporal analysis of cDNA microarray results from mature kidneys
      following IRI and during normal nephrogenesis. Molecular genetic evidence for the
      notion that regeneration recapitulates development in the kidney, and that
      injured tubule cells possess the capacity to de-differentiate to the earliest
      stages of development, is presented. The implications of these findings to the
      ability of the kidney to repair itself and potential strategies for accelerating
      recovery are briefly discussed.

PMID- 14654350
TI  - Thyroid-stimulating hormone receptor and its role in Graves' disease.
AB  - The thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR) mediates
      the activating action of TSH to the thyroid gland, resulting in the growth and
      proliferation of thyrocytes and thyroid hormone production. In Graves' disease,
      thyroid-stimulating autoantibodies can mimic TSH action and stimulate thyroid
      cells. This leads to hyperthyroidism and abnormal overproduction of thyroid
      hormone. TSHR-antibodies-binding epitopes on the receptor molecule are well
      studied. Mechanism of TSHR-autoantibodies production is more or less clear but a
      susceptibility gene, which is linked to their production, is still unknown.
      Genetic studies show no linkage between the TSHR gene and Graves' disease. Among
      three common polymorphisms in the TSHR gene, only the D727E germline polymorphism
      in the cytoplasmic tail of the receptor showed an association with the disease,
      and this association is weak. The absence of a strong genetic effect of the TSHR
      polymorphisms in such a common and complex disorder as Graves' disease may be
      explained by a high degree of evolutionary conservation in TSHR. This can be
      shown by naturally existing germline and somatic mutations in the TSHR gene that
      cause various types of nonautoimmune and hereditary thyroid disease.

PMID- 14654351
TI  - PCR methods in clinical investigations of human ureaplasmas: a minireview.
AB  - Human ureaplasmas are small, cell-wall-deficient organisms that are implicated in
      many human infections. Due to their small size and fastidious growth
      requirements, ureaplasmal infections are hard to diagnose clinically, and
      ureaplasmal disease is difficult to study in clinical samples. Standard culture
      methods for ureaplasmas are technically challenging, and 3 to 5 days are required
      to identify this pathogen. PCR methods have been increasingly used in the
      diagnosis of these infections and in the study of this pathogen in human
      specimens from multiple sites. These methods have theoretical advantages over
      traditional culture methods. Organism identification can occur in the presence of
      low numbers of bacteria, and viability is not necessary. Rapid identification of
      organisms within 24 h is also possible. In addition, subtyping of isolates can be
      performed faster with PCR methods than with culture methods. The use of PCR
      methods in translational research in multiple human ureaplasmal diseases will be
      reviewed in this paper, and their usefulness will be compared to culture methods.

PMID- 14654352
TI  - Evaluation of the therapeutic potential of PPARalpha agonists for X-linked
      adrenoleukodystrophy.
AB  - Adrenoleukodystrophy protein (ABCD1), a peroxisomal membrane protein, is mutated
      in patients affected by X-linked adrenoleukodystrophy (X-ALD).
      Adrenoleukodystrophy-related protein (ABCD2) is the closest relative of ABCD1.
      Pharmacological induction of ABCD2 gene expression has been proposed as a novel
      therapy strategy for X-ALD. Fibrates induce peroxisome proliferation and Abcd2
      expression in rodent liver. Here we evaluate the possibility of using peroxisome
      proliferator-activated receptor alpha (PPARalpha) agonists for pharmacological
      induction of ABCD2 expression. In the liver of PPARalpha-deficient mice, both the
      constitutive and the fenofibrate-inducible Abcd2 gene expression was found to be
      PPARalpha-dependent. In the brain, PPARalpha-deficiency has no effect on Abcd2
      expression. In mice orally treated with the novel, highly selective, and potent
      PPARalpha agonists GW 7647, GW 6867, and tetradecylthioacetic acid, Abcd2
      expression was induced in liver and adrenal glands, but not in brain and testis.
      None of four putative PPREs identified in the 5(')-flanking DNA and in intron 1
      of the Abcd2 gene conferred fibrate response in luciferase reporter assays. Thus,
      although fibrate-mediated Abcd2 induction is PPARalpha-dependent, it appears to
      be an indirect mechanism. Within the mouse Abcd2 promoter, a putative sterol
      regulatory element (SRE) similar in sequence and position to the characterized
      SRE sequence of the human ABCD2 promoter, was identified. A PPARalpha dependent
      induction of the sterol regulatory-binding protein 2 (SREBP2) and a down
      regulation of SREBP1c mRNA levels could be demonstrated after fenofibrate
      treatment of mice. Our results suggest that the PPARalpha agonist-mediated
      induction of Abcd2 expression seems to be indirect and possibly mediated by
      SREBP2.

PMID- 14654353
TI  - Long-term treatment of Barth syndrome with pantothenic acid: a retrospective
      study.
AB  - We report on three patients (two are brothers) with confirmed Barth syndrome
      treated with pantothenic acid. This treatment is still controversial and only one
      study has reported positive results to date. In our patients, long-term treatment
      has failed to reduce the number of infectious episodes and prevent dilated
      cardiomyopathy. Our cases show that this treatment is not as effective in Barth
      syndrome as was previously claimed.

PMID- 14654354
TI  - Characterization of the human glycerol kinase promoter: identification of a
      functional HNF-4alpha binding site and evidence for transcriptional activation.
AB  - Glycerol kinase (GK) is an enzyme at the interface of carbohydrate and fat
      metabolism. Mutations in the GK gene result in a rare inborn error of metabolism,
      GK deficiency (GKD), and at least one of these mutations (N288D) is associated
      with insulin resistance and diabetes mellitus. In an attempt to identify
      potential modifiers of the GKD phenotype, and to elucidate better the
      relationship between GKD and diabetes mellitus, we investigated the GK promoter.
      We examined the GK promoter using in silico methods, transient transfections of
      GK promoter-luciferase constructs in HepG2 hepatocellular carcinoma cells, and
      gel shift assays using liver nuclear extracts. We determined that the first 100
      bp of the GK 5(') upstream region was sufficient for basal levels of
      transcription and that there was a functional HNF-4alpha binding site in the
      first 500 bp of the 5(') upstream region that was important for increased levels
      of GK expression in vitro. The involvement of both GK and HNF-4alpha in the
      etiology of diabetes mellitus is intriguing, and we speculate that HNF-4alpha
      represents a potential modifier of the GKD phenotype.

PMID- 14654355
TI  - Studies of urinary cystine precipitation in vitro: ontogeny of cystine
      nephrolithiasis and identification of meso-2,3-dimercaptosuccinic acid as a
      potential therapy for cystinuria.
AB  - Children with fully recessive (Type I/I) cystinuria have a high risk of stone
      formation in the first decade of life. To assess the tendency for cystine to
      precipitate in individual urine samples, we developed an in vitro assay in which
      radiolabelled cystine (4mM) was dissolved in urine at 37 degrees C after
      alkalization to pH 10. Samples were then brought to pH 5, cooled, and
      centrifuged. The % decrease in supernatant cpm was used as a measure of cystine
      precipitation (CP). CP varied widely among normal children (74%+/-34) whereas
      variability of repeated determinations on a single adult individual was modest
      (64%+/-3.3). The assay was used to compare various potential therapies for
      cystinuria. Precipitation of exogenous cystine from normal urine was strongly
      inhibited by addition of D-penicillamine (CP: 8%+/-3) or dimercaptosuccinic acid
      (DMSA) (CP: 5%+/-1), at urinary concentrations attained by standard oral doses of
      each drug. Mercaptopropionylglycine (MPG) was moderately effective (CP: 43%+/-9),
      whereas captopril was a weak inhibitor (CP: 63%+/-12). Precipitation of
      endogenous cystine (2191 micromol/L) from a cystinuric patient showed that DMSA
      and D-penicillamine were again highly effective compared to the other agents. In
      addition DMSA and penicillamine added to the same patient's urine reduced the
      free cystine by 50% (as measured by automated amino acid analyzer) whereas MPG
      and captopril had no effect. In conclusion, DMSA is comparable to D-penicillamine
      as an in vitro inhibitor.

PMID- 14654356
TI  - Cell cycle dependent intracellular distribution of two spliced isoforms of
      TCP/ILF3 proteins.
AB  - TCP80 is an approximately 80kDa mammalian cytoplasmic protein that binds to a set
      of mRNAs and inhibits their translation in vitro and ex vivo. This protein has
      high sequence similarity to interleukin-2 enhancer-binding factors (NF90/ILF3)
      and the M-phase phosphoprotein (MPP4)/DRBP76. A 110kDa immunologic isoform of
      TCP80/NF90/MPP4/DRBP76, termed TCP110, also is present in cytoplasm and nuclei of
      many types of cells. A cDNA sequence coding for TCP110 was derived by 5(')RACE.
      The TCP110 sequence is identical to ILF3. The gene coding for TCP110/ILF3 mapped
      to human chromosome 19 and the gene organization was analyzed using TCP80 and
      TCP110/ILF3 cDNA sequences. The TCP/ILF3 gene spans >34.8kb and contains 21
      exons. At least one alternatively spliced product involving exons 19-21 exists
      and predicts the formation of either TCP80 or TCP110/ILF3. However, the
      functional relationships of TCP80 and TCP110/ILF3 required elucidation. The
      metabolic turnover rates and subcellular distribution of TCP80 and TCP110/ILF3
      during the cell cycle showed TCP80 to be relatively stable (t(1/2)=5 days) in the
      cytoplasmic compartment. In comparison, TCP110/ILF3 migrated between the
      cytoplasmic and nuclear compartments during the cell cycle. The TCP110 C-terminal
      segment contains an additional nuclear localizing signal that plays a role in its
      nuclear translocation. This study indicates that the multiple cellular functions,
      i.e., translation control, interleukin-2 enhancer binding, or cell division, of
      TCP/ILF3 are fulfilled by alternatively spliced isoforms.

PMID- 14654357
TI  - Improved diagnostic testing for ataxia-telangiectasia by immunoblotting of
      nuclear lysates for ATM protein expression.
AB  - The laboratory diagnosis of ataxia-telangiectasia (A-T) currently relies upon
      measurement of serum alphafetoprotein (AFP) and cellular sensitivity to ionizing
      radiation. A previous report suggests that immunoblotting of whole cell lysates
      from lymphoblastoid cell lines (LCLs) might be informative for diagnosis. To
      further evaluate this possibility, and improve sensitivity, we performed
      immunoblotting for ATM protein on nuclear lysates of 71 consecutive
      radiosensitive LCLs that were established from patients with clinical features
      suggestive of A-T. Fifty-two LCLs (73%) contained no detectable ATM protein, with
      a representative sample (N=25) testing negative for ATM kinase activity, having
      at least one ATM mutation, and having elevated AFP levels; these results
      confirmed the diagnosis. Seventeen LCLs (24%) expressed intermediate or normal
      levels of ATM protein and exhibited normal ATM kinase activity; follow-up studies
      failed to detect ATM mutations and AFP levels were normal in all but three. Of
      the remaining two radiosensitive LCLs, one had 35% of normal protein with normal
      kinase activity and no ATM mutations. The other LCL had 9% of normal protein,
      with intermediate levels of kinase activity, a homozygous missense ATM mutation,
      and elevated AFP. Our data suggest that it is very uncommon to encounter bonafide
      A-T patients with more than trace amounts of ATM protein. We conclude that
      immunoblotting for ATM protein is of higher specificity for diagnosing A-T than
      radiosensitivity testing. In addition, we have documented in vitro
      radiosensitivity in other patients who share some clinical features with A-T.

PMID- 14654359
TI  - Directed evolution towards protease-resistant hirudin variants.
AB  - Hirudin, a thrombin-specific inhibitor, is efficiently digested and inactivated
      by proteases with pepsin- and chymotrypsin-like specificity. Using a combination
      of phage display selection and high-throughput screening methods, several
      variants of recombinant hirudin were generated. Only very few variants comprising
      amino acid substitutions in the amino-terminal domain (residues 1-5) and in the
      carboxyl-terminal tail (residues 49, 50, and/or 56, 57, 62-64) were identified
      that showed thrombin inhibition activities similar to those of the wild-type
      polypeptide. Analysis of protease susceptibility, however, revealed that
      mutations, which conferred protease resistance, simultaneously diminish thrombin
      inhibition activity. This is particularly apparent for substitutions in the
      region of residues 56-64, which forms a large number of electrostatic and
      hydrophobic interactions with thrombin in the crystal structure of the complex.
      Unlike wild-type hirudin, the variant comprising Pro(50)- ...-His(56)-Asp(57)-
      ...-Pro(62)-Pro(63)-His(64) is completely resistant to pepsin and chymotrypsin
      cleavage; however, this is at the expense of thrombin inhibition activity where
      there is a 100-fold increase in the IC50 value. The frequent replacement of wild
      type amino acids by proline at major protease cleavage sites indicates that at
      least pepsin- and chymotrypsin-like enzymes may exhibit a (conformational)
      specificity concerning the P1 and P2 positions. On the basis of these results,
      proline substitutions appear to be a general strategy to design polypeptides that
      are not susceptible to digestion by a broader range of different proteases.

PMID- 14654358
TI  - Expressional pattern of chaperones in neuronal, glial, amnion, mesothelial, and
      bronchial epithelial cell lines.
AB  - Although literature is abundant on expression of individual heat shock proteins
      (HSPs) and molecular chaperones, no comprehensive information is given on their
      expressional pattern. The aim of our study was therefore to study expressional
      differences between several cell types that may provide evidence for the types of
      HSPs and chaperones that may be operating in the corresponding lineages. For this
      purpose neuronal (HCN-2), glial (SVG-p12), amnion, mesothelial (Met-5A), and
      bronchial epithelial (16HBE14o(-)) cell lines were grown, harvested, and protein
      was separated on two-dimensional electrophoresis with subsequent in-gel digestion
      and identification of protein spots by MALDI-MS and specific software. A series
      of 29 high abundance HSPs and chaperones were unambiguously identified
      altogether. We observed distinct expressional patterns and although overlapping,
      there was an apparent paucity of HSPs and chaperones in bronchial epithelial and
      mesothelial cells. We learn from this study that individual cell lines express
      and may use different HSP and chaperones systems and strategies. Specific
      functions of cells may be responsible as well as the presence of protein specific
      chaperones, although we cannot rule out that cell culture conditions were at
      least in part responsible for the different expressional patterns.

PMID- 14654360
TI  - Polymorphisms within the vitamin B12 dependent methylmalonyl-coA mutase are not
      risk factors for neural tube defects.
AB  - Methionine synthase and methylmalonyl-CoA mutase (mutase) are the only two known
      vitamin B(12) (B(12)) dependent enzymes in humans. A lower level of B(12) has
      been shown to be an independent maternal risk factor for neural tube defects
      (NTDs) prompting an investigation of common genetic variants within B(12)
      dependent enzymes. To investigate the role of methylmalonyl-CoA mutase variants
      we studied 279 complete NTD triads (NTD affected case and both parents) and 256
      controls. Based on case-control and family based (transmission disequilibrium
      test) analyses we did not find an association between the mutase single
      nucleotide polymorphisms (SNPs) K212K (636A-->G), H532R (1595A-->G) and V671I
      (2011G-->A) and NTDs. However, there was a significant difference in the
      frequencies of these polymorphisms between a group of African Americans and
      American Caucasians (K212K, P=0.002; H532R, P</=0.001; V671I, P=0.006). In
      conclusion, common variants in the mutase gene do not appear to be risk factors
      for NTDs but their allele frequencies are significantly different between ethnic
      groups.

PMID- 14654361
TI  - Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of
      vitamin D 25-hydroxylase.
AB  - Activation of vitamin D requires hepatic 25-hydroxylation and renal 1alpha
      hydroxylation. Defects in renal P450c1alpha are well-described, but few patients
      with defective vitamin D 25-hydroxylation are reported. The cytochrome P450
      enzymes CYP2D6 and CYP27 are potential 25-hydroxylases. We sequenced both genes
      in two reported families with hepatic 25-hydroxylase deficiency and found no
      mutations. 25-Hydroxylation occurs in both mitochondria and microsomes. The
      existence genes encoding distinct enzymes would provide genetic redundancy,
      explaining the rarity of apparent vitamin D 25-hydroxylase deficiency.

PMID- 14654362
TI  - A novel single nucleotide polymorphism in the 3' untranslated region of human
      retinoid X receptor gamma gene.

PMID- 14654364
TI  - Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy
      between cultured myocytes and animal models.
AB  - The mitogen-activated protein kinase (MAPK) signaling pathways serve as pivotal
      transducers of diverse biologic functions including cell growth, differentiation,
      proliferation, and apoptosis. The c-Jun N-terminal kinases (JNKs) and p38 kinases
      constitute two important branches of the greater MAPK signaling cascade that
      function as specialized transducers of stress or injury responses, hence they are
      subclassified as stress-activated protein kinases (SAPKs). In the myocardium,
      both p38 and JNK transduction cascades have been implicated in regulating the
      hypertrophic response, as well as cardiomyopathy and heart failure. Most reports
      proposing a pro-hypertrophic regulatory role for JNK and p38 signaling placed a
      heavy or exclusive reliance on culture-based models of cellular growth. More
      recently, a number of studies in genetically modified animal models have
      challenged the previously proposed role of JNK and p38 as pro-hypertrophic
      signaling effectors in the myocardium. This review will discuss an increasing
      body of evidence suggesting that the SAPKs (JNK and p38) do not positively
      regulate cardiac hypertrophy in vivo, but in fact may actually serve as negative
      regulators of this response in the adult heart. However, SAPK signaling is likely
      maladaptive, despite its putative anti-hypertrophic role in vivo, given the
      observation of dilated cardiomyopathy and heart failure in gain-of-function
      transgenic models.

PMID- 14654365
TI  - Remodeling of cardiac inward-rectifier currents: an often-overlooked contributor
      to arrhythmogenic states.

PMID- 14654366
TI  - Decreased ATP-sensitive K(+) current density during chronic human atrial
      fibrillation.
AB  - Chronic atrial fibrillation (AF) is associated with shortening of action
      potential duration (APD), which involves modified activity of atrial ion
      currents. However, little is known about the activity of ATP-sensitive K(+)
      channels (I(K,ATP)) during chronic AF. An AF-related increase in the activity of
      I(K,ATP) would reduce APD and could contribute to initiation and/or perpetuation
      of AF. Here, we studied the activity of I(K,ATP) in atrial myocytes from patients
      with sinus rhythm (SR) and chronic AF. Human atrial myocytes were isolated from
      atrial tissue obtained from patients undergoing open-heart surgery. Inward
      rectifier currents were measured with the whole-cell patch-clamp technique by
      applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz).
      I(K,ATP) was activated with the I(K,ATP) channel opener rilmakalim. The inward
      rectifier I(K1) and I(K,ATP) were identified by their sensitivity to 1 mM Ba(2+).
      Density of I(K1) did not differ between cells from patients with AF (at -100 mV: 
      14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n =
      33/16). In both types of cells, rilmakalim stimulated I(K,ATP) (defined as
      rilmakalim-inducible current) in a concentration-dependent manner (0.3-10
      microM). However, maximum activation of I(K,ATP) with 10 microM rilmakalim was
      smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. 
      11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF, n = 22/7 vs. +23.7
      +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve
      disease and pulmonary hypertension were found to be independent contributors to
      I(K,ATP) current density. We provide evidence that chronic AF is associated with
      a downregulation of ATP-sensitive K(+) currents. These changes may provide an
      additional molecular mechanism for electrical remodeling in chronic AF.

PMID- 14654367
TI  - Interaction of Smad3 and SRF-associated complex mediates TGF-beta1 signals to
      regulate SM22 transcription during myofibroblast differentiation.
AB  - Myofibroblasts play important roles in a variety of developmental and
      pathological processes, such as vascular remodeling, atherosclerosis and wound
      healing. In this study, we used the TGF-beta1-treated 10T1/2 cells as an in vitro
      model to understand how Smad-mediated TGF-beta1 signals regulate SM22 promoter
      transcription during myofibroblast differentiation. We found that TGF-beta1
      transiently induces SRF and SM22 transcription, and that this process is
      accompanied by transient increases of SRF and Smad3 binding to the SM22 promoter.
      Interestingly, Smad3, not Smad2, is the primary mediator for TGF-beta1-induced
      transactivation of the SM22 promoter, while Smad6 and Smad7 repress such a
      transactivation. Smad3 can bind to a Smad-binding element (SBE) in the first exon
      of SM22, and directly associate with the SRF complex in response to TGF-beta1
      treatment. Moreover, Smad3 and I-Smads regulate the SM22 promoter through CArG
      box-dependent transcription using dominant-negative SRF mutants and SRF-VP16.
      Although SBE as well as CArG boxes and TGF-beta control element are all important
      for the SM22 promoter activities, the promoters with mutations at either one or
      all of them still respond to TGF-beta1 treatment. Consistently, TGF-beta1
      stimulates SM22 transcription in Smad3 null mouse embryonic fibroblasts. These
      findings provide the first evidence that Smad3 directly links TGF-beta1 signaling
      to an SRF-associated regulatory network in controlling SM22 transcription; it
      also implies that TGF-beta1 regulates the SM22 promoter via Smad3-dependent and
      Smad3-independent pathways.

PMID- 14654368
TI  - Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the
      troponin T-tropomyosin interaction and causes a Ca2+ desensitization.
AB  - A missense mutation R141W in the strong tropomyosin-binding region of cardiac
      troponin T (cTnT) has recently been reported to cause dilated cardiomyopathy
      (DCM), following the first report of a DCM-causing deletion mutation DeltaK210.
      To clarify the molecular mechanism for the pathogenesis of DCM caused by this
      novel mutation in cTnT gene, functional analyses were made on the recombinant
      human cTnT mutant proteins. Exchanging human wild-type and mutant cTnTs into
      rabbit skinned cardiac muscle fibers revealed that R141W mutation resulted in a
      decrease in the Ca(2+) sensitivity of force generation, as in the case of
      DeltaK210 mutation lying outside the strong tropomyosin-binding region. In
      contrast, a missense mutation R94L in the vicinity of the strong tropomyosin
      binding region associated with hypertrophic cardiomyopathy (HCM) resulted in an
      increase in the Ca(2+) sensitivity of force generation, as in the case of the
      other HCM-causing mutations in cTnT reported previously. An assay using a quartz
      crystal microbalance (a very sensitive mass-measuring device) revealed that R141W
      mutation increased the affinity of cTnT for alpha-tropomyosin by approximately
      three times, whereas an HCM-causing mutation DeltaE160 in the strong tropomyosin
      binding region, as well as DeltaK210 and R94L mutations, had no effects on the
      interaction between cTnT and alpha-tropomyosin. Since cTnT has an important role
      in structurally integrating cardiac troponin I (cTnI) into the thin filaments via
      its two-way interactions with cTnI and tropomyosin, the present results suggest
      that R141W mutation in the strong tropomyosin-binding region in cTnT strengthens
      the integrity of cTnI in the thin filament by stabilizing the interaction between
      cTnT and tropomyosin, which might allow cTnI to inhibit the thin filament more
      effectively, leading to a Ca(2+) desensitization.

PMID- 14654369
TI  - Effect of tachycardia on myocardial sarcoplasmic reticulum and Ca2+ dynamics: a
      mechanism for preconditioning?
AB  - We have previously demonstrated that brief episodes of tachycardia prior to a
      prolonged occlusion of a coronary artery, followed by reperfusion, substantially
      reduce the infarct size. Adenosine receptors and mitochondrial ATP-dependent K(+)
      channels mediate this effect. Since preconditioning can be induced or reverted by
      maneuvers that increase or decrease [Ca(2+)](i), respectively, and tachycardia
      increases [Ca(2+)](i), we studied the participation of sarcoplasmic reticulum and
      Ca(2+) in the preconditioning effect of tachycardia. We measured the effect of
      ischemia and tachycardia on Ca(2+) uptake and release by sarcoplasmic reticulum
      vesicles isolated from left ventricular canine myocardium. Myocardial ischemia
      increased Ca(2+)-release rate constants and decreased both the initial rates of
      Ca(2+) uptake and [(3)H]-ryanodine binding by sarcoplasmic reticulum. In
      addition, ischemia induced a decrease in the pentameric form of phospholamban and
      in the content of ryanodine-receptor Ca(2+)-release channel protein. All these
      effects were reverted in hearts preconditioned with tachycardia. Furthermore,
      tachycardia by itself increased [(3)H]-ryanodine binding, Ca(2+)-release rate
      constants and the protein levels of ryanodine-receptor Ca(2+)-release channels
      and the ATP-dependent Ca(2+) pump. These results suggest that tachycardia
      preserves the integrity of the sarcoplasmic reticulum preventing the excess of
      release and the decrease of uptake of Ca(2+) produced by ischemia, thereby
      avoiding cytosolic Ca(2+) overload. This sarcoplasmic reticulum protection could
      partly explain the preconditioning effect of tachycardia.

PMID- 14654370
TI  - Heme oxygenase in diabetes-induced oxidative stress in the heart.
AB  - Diabetic cardiomyopathy is responsible for substantial morbidity and mortality in
      the diabetic population. Increased oxidative stress has been associated with the
      pathogenesis of chronic diabetic complications including cardiomyopathy. Multiple
      biochemical mechanisms have been proposed to increase oxidative stress in
      diabetes. The present study was aimed at elucidating the role of a potent
      oxidative and cellular stress-responsive system, the heme oxygenase (HO) system,
      in the heart in diabetes. Streptozotocin-induced diabetic rats were treated with
      a potent inhibitor of HO system, tin protoporphyrin IX (SnPPIX, 50
      micromol/kg/d), and were compared with untreated diabetic and non-diabetic
      animals. All treatments began at the onset of diabetes, 48 h after injection of
      streptozotocin along with the confirmation of hyperglycemia. Animals were
      euthanized after 1 week and 1 month of treatment, and heart tissues were
      harvested. Frozen tissues were subjected to HO-1 and HO-2 mRNA expression by real
      time RT-PCR and HO activity determination. Paraffin-embedded tissue sections were
      used for immunohistochemical analysis of HO-1 and HO-2. 8-Hydroxy-2'
      deoxyguanosine (8-OHdG) stain, a sensitive and specific marker of DNA damage, was
      preformed to assess damage induced by oxidative stress. In addition, tissue
      sections were subjected to histochemical analysis for iron. We further examined
      non-diabetic animals treated with a direct HO agonist, hemin (50 mg/kg/d). A
      possible relationship between the HO and the nitric oxide (NO) pathways was also
      considered by studying the mRNA levels of endothelial nitric oxide synthase (NOS)
      and inducible NOS, and by measuring the amount of NOS products. Our results
      demonstrate no significant alterations of the HO system following 1 week of
      diabetes. However, 1 month of diabetes caused increased oxidative stress as
      demonstrated by higher levels of 8-OHdG-positive cardiomyocytes (80% positive as
      compared to 11.25% in controls), in association with increased HO isozyme mRNA
      (2.7-fold increase as compared to controls) and protein expression, and augmented
      HO activity (759.3 as compared to 312.3 pmol BR/h/mg protein in controls).
      Diabetic rats further demonstrated increased number of cardiomyocytes with
      stainable iron. SnPPIX treatment resulted in reduced number of 8-OHdG-positive
      cardiomyocytes (19.5% as compared to 80% in diabetics) in parallel with reduced
      HO activity (569.7 as compared to 759.3 pmol BR/h/mg protein in diabetics). Non
      diabetic rats treated with HO-agonist hemin exhibited abnormalities similar to
      diabetic rats. Our results provide the first direct demonstration that diabetes
      induced oxidative stress in the heart is, in part, due to upregulated HO
      expression and activity. These results provide evidence of pro-oxidant activity
      of HO in the heart in diabetes, which could be mediated by increased redox-active
      iron.

PMID- 14654371
TI  - Effects of pravastatin on cardiomyocyte hypertrophy and ventricular vulnerability
      in normolipidemic rats after myocardial infarction.
AB  - Reactive cardiomyocyte hypertrophy after myocardial infarction (MI) is an
      important risk factor for arrhythmias. Endothelin (ET)-1 has been implicated in
      the development of cardiac hypertrophy. We investigated the effect of pravastatin
      on ventricular hypertrophy during remodeling after MI and whether the attenuated
      hypertrophic effect was via reduced regional ET-1 expression. After ligation of
      the anterior descending artery, male Wistar rats were randomized to either
      vehicle, pravastatin, mevalonate, or a combination of the two drugs for 4 weeks.
      Sham operation served as controls. Pravastatin decreased cardiomyocyte sizes
      isolated by enzymatic dissociation at the border zone. The myocardial ET-1 levels
      at the border zone were 6.3-fold higher (P < 0.0001) in the vehicle group
      compared with sham group. The increased regional ET-1 levels can be inhibited
      after pravastatin administration. Immunohistochemical analysis confirmed the
      localization of ET-1 mainly in the cardiomyocytes. This was paralleled by a 9.8
      +/- 2.3-fold upregulation of preproET-1 mRNA assessed by real-time quantitative
      reverse transcription-polymerase chain reaction in the vehicle-treated rats,
      which reduced after administering pravastatin. Cardiomyocyte sizes at the border
      zone correlated positively with regional ET-1 levels (P = 0.001). Arrhythmic
      scores during programmed stimulation were significantly higher in the vehicle
      group than in the pravastatin-treated group (3.0 +/- 1.3 vs. 1.3 +/- 1.0, P <
      0.0001). In contrast, pravastatin-induced effects were reversed by the addition
      of mevalonate, implicating 3-hydroxy-3-methyglutaryl-CoA reductase as the
      relevant target. The results of the present study suggest that the pravastatin
      administration after infarction can reduce the inducibility of ventricular
      arrhythmias as a result of attenuated cardiomyocyte hypertrophy probably through
      decreased tissue ET-1 level, which is linked to mevalonate metabolism.

PMID- 14654372
TI  - Cardiomyocytes purified from differentiated embryonic stem cells exhibit
      characteristics of early chamber myocardium.
AB  - Mouse embryonic stem (ES) cells easily differentiate towards the cardiac lineage
      making them suitable as an in vitro model to study cardiogenesis and as a
      potential source of transplantable cells. In this study, we show by in situ
      hybridisation that about 30% of the volume of cultures of differentiating ES
      cells consists of cardiomyocytes. RT-PCR analyses showed that the transcription
      factors Nkx2.5, Gata4, Mef2c and Irx4 were expressed at levels in the same order
      of magnitude as the levels observed in embryonic, neonatal and adult hearts.
      Atrial natriuretic factor and Connexin 40, associated with chamber formation in
      vivo, are expressed at relatively low levels, similar to those observed at early
      heart development in vivo. To facilitate the isolation of ES cell-derived
      cardiomyocytes, a cell line was constructed by stable transfection of the
      aminoglycoside phosphotransferase cDNA driven by the cardiac-specific distant
      upstream part of the Na(+)/Ca(2+) exchanger promoter. To accomplish single-copy
      integration, the construct was inserted into the hypoxanthine
      phosphoribosyltransferase locus of HM1 ES cells by homologous recombination.
      Cardiac-specific resistance to G418-sulphate (neomycin) allowed isolation of a
      pure population of cardiomyocytes. Genetically selected and unselected cell
      populations were characterised electrophysiologically using patch clamp. To
      explore whether clusters of cells have a similar differentiation profile, action
      potentials (APs) were measured in aggregates of differentiating ES cells, using a
      new method based on the voltage-dependent fluorescent dye di-4-ANEPPS. Both whole
      cell recordings using patch-clamp and optical measurements with di-4-ANEPPS of
      the AP showed that upstroke velocity increases and AP duration decreases with
      differentiation time, accompanied by a decrease in AP interval, suggesting the
      initiation of the developmental programme underlying the formation of chamber
      myocardium.

PMID- 14654373
TI  - Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis
      via erbB4-dependent activation of PI3-kinase/Akt.
AB  - We have found that neuregulin-1beta (NRG-1beta) is expressed in the cardiac
      microvascular endothelium, and promotes the growth and survival of cardiac
      myocytes in culture through the activation of erbB2 and erbB4 receptor tyrosine
      kinases. In this study, we examined the role of NRG-1/erbB signaling in
      protection of cardiac myocytes from anthracycline-induced apoptosis in vitro to
      determine the coupling between erbB receptor subtypes and cytoprotective
      signaling. Treatment of neonatal rat ventricular myocytes with NRG-1beta
      inhibited daunorubicin-induced apoptosis as shown by terminal
      deoxynucleotidyltransferase-mediated dUTP nick end-labeling staining for DNA
      fragmentation as well as flow cytometric quantification of apoptotic myocytes.
      Daunorubicin-induced activation of caspase-3 in cardiomyocytes was similarly
      inhibited by NRG-1beta. The phosphoinositol-3-kinase (PI3-kinase) inhibitor
      wortmannin prevented the effects of NRG-1beta on daunorubicin-induced apoptosis
      and activation of caspase-3. NRG-1beta treatment induced rapid activation of
      Akt/PKB that was inhibited by wortmannin, and adenoviral-mediated overexpression
      of a dominant-negative Akt prevented the protective effect of NRG-1beta. Akt
      activation by NRG-1beta was prevented by the tyrphostin AG1478, which we show
      inhibits erbB4 activation by NRG-1beta. In contrast, the erbB2-specific
      tyrphostin AG879 had no effect on NRG-1beta activation of Akt. Myocyte treatment
      with an activating antibody to erbB2 caused phosphorylation of erbB2, and led to
      activation of Erk but not Akt. Treatment with the erbB2 antibody had no effect on
      anthracycline-induced apoptosis. Thus, NRG-1beta protects against anthracycline
      induced apoptosis via erbB4-dependent activation of the PI3-kinase/Akt pathway.

PMID- 14654374
TI  - Reoxygenation-induced rigor-type contracture.
AB  - The hypothesis tested was that reoxygenation-induced contracture of myocardial
      cells, a form of reperfusion injury, can be due to a rigor-type mechanism.
      Isolated adult cardiomyocytes were exposed to 30- or 60-min anoxia (pH 6.4) and
      reoxygenation (pH 7.4). In cardiomyocytes, cytosolic Ca(2+) and cell length, and
      in isolated rat hearts left ventricular end-diastolic pressure (LVEDP) were
      measured. During reoxygenation, cardiomyocytes developed contracture. When energy
      recovery was slowed down, less Ca(2+) overload was required for contracture: (1)
      after 30-min anoxia Ca(20) (cytosolic Ca(2+) concentration in cells with 20% cell
      length reduction) was 1.42 +/- 0.11 micromol/l; (2) after 30-min anoxia with
      partial mitochondrial inhibition during reoxygenation (NaCN, 0.1 mmol/l) Ca(20)
      was reduced to 0.69 +/- 0.05 micromol/l; (3) after 60-min anoxia Ca(20) was
      reduced to 0.78 +/- 0.05 micromol/l and (4) when energy recovery was accelerated
      (succinate, 0.2 mmol/l), Ca(20) rose to 1.35 +/- 0.05 micromol/l. In isolated
      hearts, the reperfusion-induced rise in LVEDP was modulated by the same
      interventions. Slow recovery of energy production favors reoxygenation-induced
      contracture in cardiomyocytes and hearts. This shows that rigor contracture
      contributes to reoxygenation-induced cell injury.

PMID- 14654375
TI  - Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes.
AB  - In the present study, we examined the effect of interleukin-2 (IL-2) on
      cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes
      in stimulation frequency on the intracellular Ca(2+) transient were investigated
      in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2
      Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by
      electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+)
      concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to
      1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration
      ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive
      frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were
      blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically
      induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5
      mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release.
      Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted
      in a significant reduction of the amplitude-frequency relationship of the
      transient similar to that induced by IL-2. The restitutions were not different
      between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2
      treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no
      difference in the recirculation fraction (RF) between control and IL-2-treated
      myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency
      relationship, restitution, and RF may be due to depressed SR functions and an
      increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+)
      channels.

PMID- 14654376
TI  - Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes
      through activation of mitochondrial ATP-sensitive potassium channels and a
      nitrate-like effect.
AB  - The anti-anginal drug nicorandil has been shown to inhibit apoptosis by
      activating mitochondrial ATP-sensitive potassium (K(ATP)) channels. The possible
      contribution of the nitrate moiety of this drug to its anti-apoptotic effect has
      now been investigated in neonatal rat ventricular myocytes subjected to oxidative
      stress. Exposure of cultured myocytes to 100 micromol/l hydrogen peroxide
      (H(2)O(2)) increased the number of nuclei stained by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique as well as
      induced internucleosomal DNA fragmentation, loss of mitochondrial membrane
      potential, cytochrome c release into the cytosol, and activation of caspases-3
      and -9, all of which are characteristics of apoptosis. Pretreatment of cells with
      nicorandil (100 micromol/l) inhibited these effects of H(2)O(2). Both the
      mitochondrial K(ATP) channel antagonist 5-hydroxydecanoate (5-HD) and 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl
      cyclase, attenuated the anti-apoptotic effect of nicorandil in concentration
      dependent manners. Coapplication of ODQ (10 micromol/l) and 5-HD (500 micromol/l)
      completely abolished nicorandil-induced cytoprotection. The effect of nicorandil
      was also reduced by an inhibitor of cGMP-dependent protein kinase (KT5823, 1
      micromol/l). The nitric oxide donor (+/-)-S-nitroso-N-acetylpenicillamine (SNAP,
      50 micromol/l) mimicked the protective effect of nicorandil in a manner sensitive
      to ODQ but not to 5-HD. A cell-permeable cGMP analog, 8-bromo-cGMP, also reduced
      H(2)O(2)-induced apoptosis. The inhibition of the H(2)O(2)-induced activation of
      caspase-3, but not that of caspase-9, by nicorandil in the presence of 5-HD or by
      SNAP was reversed by the addition of dithiothreitol to the enzyme assay.
      Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes
      through a nitric oxide/cGMP-dependent mechanism as well as by activating
      mitochondrial K(ATP) channels.

PMID- 14654377
TI  - A novel mutation in SCN5A, delQKP 1507-1509, causing long QT syndrome: role of
      Q1507 residue in sodium channel inactivation.
AB  - Inherited long QT syndrome (LQTS) is caused by mutations in six genes including
      SCN5A, encoding the alpha-subunit of the human cardiac voltage-dependent sodium
      channel hNa(v)1.5. In LQT3, various mutations in SCN5A were identified, which
      produce a gain of channel function. The aim of this study was to screen SCN5A for
      mutations in a family with the LQT3 phenotype and to analyze the consequences of
      the mutation on the channel function. By polymerase chain reaction-denaturating
      high performance liquid chromatography-sequencing, we identified a novel deletion
      in SCN5A, delQKP 1507-1509, in the DIII-DIV linker of the sodium channel. The
      hNa(v)1.5/delQKP1507-1509, hNa(v)1.5/delQ1507 and hNa(v)1.5/Q1507A mutants were
      constructed in vitro, mutant channels were expressed in the tsA201 human cell
      line and studied using the whole-cell configuration of the patch clamp technique.
      A persistent inward sodium current of 1-1.5% of maximum currents measured at -30
      mV in all mutant sodium channels was recorded, which was nearly completely
      blocked by the sodium-channel blockers tetrodotoxin and lidocaine. The deletion
      mutants resulted in a significant shift of steady-state activation to more
      depolarized voltages. The delQ1507 showed a small shift of steady-state
      inactivation towards more negative potentials, whereas no significant shifts were
      observed in both steady-state activation and inactivation in Q1507A compared to
      the wild-type Na(v)1.5 sodium channels. The novel SCN5A mutation, delQKP, induces
      a residual current as previously shown for other SCN5A mutations causing LQTS.
      DelQKP shares the deletion of Q1507 with the formerly known delKPQ 1505-1507. Our
      data suggest that Q1507 plays an important role in fast sodium channel
      inactivation.

PMID- 14654378
TI  - Tumor necrosis factor-induced protection of the murine heart is independent of
      p38-MAPK activation.
AB  - Brief exposure to tumor necrosis factor (TNF) is known to trigger subsequent
      cardioprotection. TNF activates multiple downstream signaling cascades including
      p38-MAPK, a kinase known to initiate ischemic preconditioning. However, it is not
      known whether this kinase is similarly involved in TNF-induced cardioprotection.
      In isolated perfused murine hearts, subjected to 30-min global ischemia/2-h
      reperfusion, infarction/risk volume was significantly reduced by pretreatment
      with TNF for 15 min at 0.5 ng/ml, but not at 5 or 10 ng/ml, followed by 10-min
      washout vs. control (% I/R = 31 +/- 3, 46 +/- 5 or 54 +/- 3 vs. 48 +/- 5; P =
      0.01, 0.80 and 0.25, respectively). This was in direct contrast to the
      concentration dependence of myocardial p38-MAPK phosphorylation, as measured by
      dual phosphorylated p38-MAPK, which was apparent at TNF concentrations of 5 and
      10 ng/ml but not at 0.5 ng/ml vs. time-matched control (as % basal 315 +/- 25,
      422 +/- 94 and 97 +/- 25 vs. 95 +/- 10; P < 0.01, 0.01 and =0.86, respectively).
      However, phosphorylation of p38-MAPK at 10 min of ischemia was similar among
      groups (as % basal 393 +/- 98, 410 +/- 67 and 369 +/- 49 for time-matched
      control, 0.5 and 5 ng/ml, respectively). These patterns were also reflected in
      the phosphorylation of the downstream substrate HSP27. Furthermore, the effects
      of TNF on infarct size were not affected by SB203580 (1 micromol/l). These
      findings suggest that the pre-ischemic activation of p38-MAPK by TNF does not
      contribute to cardioprotection afforded by this agent.

PMID- 14654381
TI  - Evidence-based guidelines for preventing healthcare-associated infections in
      primary and community care in England.

PMID- 14654382
TI  - Adsorption, separation, and thermochemical data on the herbicide picloram
      anchored on silica gel and its cation interaction behavior.
AB  - The herbicide 4-amino-3,5,6-trichloropicolinic acid (picloram), chemically
      anchored on silica gel surface (SiPi), has been used for divalent cation M(2+)
      (Cu, Ni, Zn, and Cd) adsorption from aqueous solutions at room temperature. The
      series of adsorption isotherms were adjusted to a modified Langmuir equation from
      data obtained by suspending the solid with MCl(2) solutions, which gave the
      maximum number of moles adsorbed as 9.27, 7.54, 5.12, and 1.54 x 10(-4) molg(-1)
      for Cu, Ni, Zn, and Cd, respectively. The minimum cation retention capacity from
      aqueous solution was observed at pH 1, increasing up to pH 4, and was maintained
      constant at pH 5 for all cations. The maximum retention capacity followed the
      sequence Cu>Ni>Zn>Cd. SiPi-M (Cu, Ni) interactions presented endothermic
      enthalpic values, which contrasted with exothermic values for SiPi-M (Zn, Cd)
      interactions. The anchored herbicide was also used to separate the cations when
      loaded in a column. Their resolutions were determined as the ability of this
      surface to separate cations, to give Rs(Cd-Zn)=2.33, Rs(Cd-Ni)=3.16, Rs(Cd
      Cu)=7.21, Rs(Zn-Ni)=1.31, Rs(Zn-Cu)=2.55, and Rs(Ni-Cu)=0.72.

PMID- 14654383
TI  - Adsorption of phenanthrene on organoclays from distilled and saline water.
AB  - Isotherms of phenanthrene adsorption on different organoclay complexes were
      obtained using the HPLC technique to understand the adsorption behavior and to
      characterize the effect of sodium chloride (NaCl) on the adsorption. The adsorbed
      amounts of phenanthrene on montmorillonite exchanged by organic cations such as
      tetraheptylammonium, benzyltrimethylammonium, hexadecyltrimethylammonium, or
      tetraphenylphosphonium were several times higher than those obtained using
      montmorillonite clay without surface modification. At the same equilibrium
      concentration, the adsorbed amount of phenanthrene is higher on clay modified
      with benzyltrimethylammonium than on clay modified with
      hexadecyltrimethylammonium or other cations. Adsorption of phenanthrene on clay
      modified with benzyltrimethylammonium increased dramatically as the concentration
      of NaCl increased up to 150 g/l in the aqueous solution. The shape of the curves
      obtained can be classified as S-type. The adsorption data obtained from salinity
      experiments support a mathematical model that links the Langmuir constant with
      the salinity constant. This model may be useful to predict the equilibrium
      concentration of a contaminant in saline solution. FTIR studies showed strong
      interactions between the aromatic rings of phenanthrene and the preadsorbed
      benzyltrimethylammonium on clay surfaces.

PMID- 14654384
TI  - Effect of solubility on the determination of the protonable surface site density
      of oxyhydroxides.
AB  - The impact of the dissolved quantity of aluminum on the calculation of surface
      charge from titration experiments of hydrated gamma-alumina was investigated. Two
      methods were developed to correct this effect: direct determination of aluminum
      in solution in batch titration experiments and application of a dissolution rate
      model in continuous titration experiments. There is a large effect of dissolution
      on surface charge determination for pH>10 and pH < 4.5. Application of these
      correction methods to these pH ranges lead to apparent saturation surface charges
      of 1.3 and 2.3 at nm(-2), respectively. The last value seems to be the real
      proton-active site density, while the hydroxyl-active site density cannot be
      reached for easily achievable basic pH values.

PMID- 14654385
TI  - Gaseous adsorption properties of a silica-pillared layered manganese oxide.
AB  - Adsorptions of N(2), H(2)O, and organic vapors including CH(2)Cl(2), CCl(4), c
      C(6)H(12), C(6)H(6), n-C(6)H(14), and n-C(9)H(20) on a silica-pillared layered
      manganese oxide (SiHMnO) and nonane-preadsorbed SiHMnO were examined. It is found
      that SiHMnO has a microporosity with a wide pore width distribution showing
      different pore wall affinities. Micropores with smaller width preferentially
      accommodate the nonane preadsorbate while the surface hydrophilicity of pore wall
      leads to an easier detachment of the adsorbed nonane molecules. H(2)O adsorption
      influences both the porosity and the surface properties by accelerating a
      sufficient hydrolysis of the remained TEOS molecules in SiHMnO. Examinations
      using Dubinin-Radeshkevich (DR) equation and isosteric heat of adsorption of
      organic molecules provide evidences that the wall surface of micropores with
      smaller and larger width have less affinity toward nonpolar and polar organic
      vapors, respectively.

PMID- 14654386
TI  - Adsorption isotherms of 2,2,4-trimethylpentane and toluene vapors on hydrocarbon
      adsorber and light-off catalyst.
AB  - Two monolithic hydrocarbon adsorbers and a monolithic light-off catalyst were
      selected as adsorbents, and the adsorptive capacity of a hydrocarbon for the
      adsorbents was measured by using a precise volumetric adsorption apparatus. 2,2,4
      Trimethylpentane and toluene vapors were chosen as adsorbates. Equilibrium
      experiments were carried out at three different temperatures of 303.15, 323.15,
      and 343.15 K. Adsorption data of each hydrocarbon was fitted to the well-known
      isotherms such as the Langmuir equation and the Freundlich equation. The
      Freundlich isotherm predicted equilibrium data better than the Langmuir isotherm.
      Furthermore, the surface energetic heterogeneity of the adsorbents was evaluated
      using the isosteric heat of adsorption based on Clausius-Clapeyron equation. The
      surface energetic heterogeneity of the adsorbents depended on the precious metal
      (PM) loading and H-ZSM5 loading.

PMID- 14654387
TI  - Study of copper adsorption on montmorillonites using thermal analysis methods.
AB  - Copper was adsorbed onto Ca-exchanged montmorillonite (Cheto clay) under basic
      conditions. Differential thermogravimetric analysis (DTGA) combined with evolved
      gas mass spectroscopy (MS) was employed as the principal technology to study the
      distribution and structure of adsorbed copper species on the montmorillonite
      clay. The results showed that the original clay was easily rehydrated. After
      copper adsorption, a step-by-step replacement of hydrated calcium ions by copper
      ammonia complex was observed through the gradual decrease of the first DTGA
      dehydration peak intensity with increasing copper loading. Compared with the
      original clay, copper loaded samples showed new DTGA peaks assigned to NH(3) and
      N(2)O. The presence of the N(2)O peak suggested that the loaded copper species
      were in agglomerated copper oxide form, which dispersed well over the edges and
      external surfaces of the clay layers.

PMID- 14654388
TI  - Copper (II) adsorption from aqueous solution by herbaceous peat.
AB  - In this research, the herbaceous peat collected from Gavurgolu peatlands, one of
      the biggest Turkish peatlands, was utilized as an adsorbent for the removal of
      copper (II) ions from aqueous solution. Adsorption experiments were conducted
      under various conditions, i.e., initial concentration, temperature, and pH. While
      the amount of Cu (II) adsorbed on the peat increased with increasing
      concentration of Cu (II) ions, it was not markedly affected by temperature and
      pH. Percentage removal was higher at lower concentration. For example, the
      maximum percentage removal of Cu (II) ions for initial concentration of 3 x 10(
      4) M was 97.04% at 21 degrees C and pH 5.5. The adsorption capacity (Q(0)) of the
      peat was 4.84 mgg(-1) from Langmuir adsorption isotherm for the concentration
      range of 3 x 10(-4)-6 x 10(-4) M at 21 degrees C and pH 5.5. The equilibrium time
      of adsorption of Cu (II) ions was 150 min and independent of concentration and
      temperature. The amount of Cu (II) adsorbed at equilibrium time did not
      considerably change with temperature and pH. It was also determined that
      adsorption isotherm followed both Freundlich and Langmuir. Uptake mechanism of Cu
      (II) ions by the peat occurs via cation exchange (especially by means of Ca(2+)
      and Mg(2+)) as well as copper/peat complexation. Adsorption kinetic was
      consistent with the pseudo-second-order model.

PMID- 14654389
TI  - Determination of adsorptive properties of clay/water system: methylene blue
      sorption.
AB  - In this study, adsorption of methylene blue onto clay was investigated. The
      effect of adsorption time and temperature on the adsorption process was studied.
      To reveal the adsorptive characteristics of the clay studied, porosity and BET
      surface area measurements were made. It was observed that the adsorption capacity
      decreases with increasing temperature, and adsorption equilibrium was attained
      within 1 h. It was found that the data fit well to Langmuir, Halsey, Henderson,
      and Harkins-Jura models but experimental data deviate significantly from BET and
      Freundlich models at especially high concentrations. Furthermore, isosteric
      adsorption enthalpy and entropy are calculated as -7.99 kJ mol(-1) and 25.41 JK(
      1)mol(-1), respectively.

PMID- 14654390
TI  - Anion specific adsorption on Fe2O3 and AlOOH nanoparticles in aqueous solutions:
      comparison with hematite and gamma-Al2O3.
AB  - The specific adsorption of radiolabeled sulfate and phosphate ions from
      perchlorate supporting electrolyte onto nano-AlOOH and nano-Fe(2)O(3) powder has
      been investigated. The pH dependence of the adsorption of anions onto nanopowders
      was compared with that of the same ions onto gamma-Al(2)O(3) and hematite. It was
      demonstrated that the character of the pH dependence of the adsorption is very
      similar in the comparable cases. It was found, however, that in contrast to the
      behavior of gamma-Al(2)O(3), nano-AlOOH dissolves at a significant rate at low pH
      values (pH<2). Thus the study of the pH dependence of the anion adsorption
      encounters difficulties at these pH values. Disregarding this fact, it can be
      concluded that no special effects can be observed in the anion adsorption onto
      the nano-oxides studied.

PMID- 14654391
TI  - Specific influence of univalent cations on the ionization of alumina-coated TiO2
      particles and on the adsorption of poly(acrylic)acid.
AB  - A surface counterion titration method was used to monitor the interaction of
      monovalents cations (Li(+), Na(+), TMA(+)) with the surface of alumina-coated
      TiO(2) particles in concentrated media at different pH and electrolyte
      concentrations. This method allows measuring separately the negative and positive
      contribution to the surface charge. It showed that Cl(-) and TMA(+) are
      indifferent ions, but Li(+) and Na(+) specifically adsorb on the non-ionized
      alumina surface sites. The binding sequence of cations is Li(+)>Na(+)>TMA(+) at
      all ionic strengths investigated and is consistent with the structure-making and
      structure-breaking model developed a few decades ago. Polyacrylic acid (PAA)
      previously neutralized with the corresponding hydroxide (LiOH, NaOH, TMAOH) has
      been adsorbed on the alumina surface at different pH. The polymer counterion has
      a significant influence on the polymer adsorption. The sequence of the surface
      coverage as a function of the polymer counterion follows the order Li-PAA > Na
      PAA > TMA-PAA. The much higher surface coverage with Li-PAA and Na-PAA compared
      to TMA-PAA is explained by the specific adsorption of Li-PAA and Na-PAA on the
      nonionized alumina surface sites, the same way LiCl and NaCl do.

PMID- 14654392
TI  - Atomic force microscopy imaging of hair: correlations between surface potential
      and wetting at the nanometer scale.
AB  - We report investigations of hair surface potential under wetting at the
      nanometric scale by atomic force microscopy (AFM). Surface potential imaging was
      used to characterize the electrostatic properties of the hair samples. We found
      that the surface potential noticeably increases along the edges of the cuticles.
      These results are correlated with wetting behavior of different liquids performed
      using AFM in noncontact mode.

PMID- 14654393
TI  - Surface morphology and biological activity of protein thin films produced by
      electrospray deposition.
AB  - Protein thin films were prepared by the electrospray deposition (ESD) method from
      aqueous solutions of alpha-lactalbumin (alpha-LA) at different concentrations,
      and their surface morphologies and biological activities were characterized. The
      surface morphologies of the deposited films were observed using scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). The SEM and AFM images showed
      that the film surfaces had a fine porous structure, in which the pore diameters
      ranged from 40 to 600 nm. The biological activities of the cross-linked protein
      films were tested by the mechanochemical method. The response to calcium ion
      (Ca(2+)) demonstrated that the biological activity of the films was preserved.
      These results indicate that the ESD method is potentially useful for the
      fabrication of active protein thin films. The freestanding protein thin films
      prepared by ESD and postdeposition cross-linking provide novel options for
      protein-based biomaterials.

PMID- 14654394
TI  - Morphology and internal structure of barium sulfate--derivation of a new growth
      mechanism.
AB  - Particle formation is the decisive step to control crystal morphology. Besides
      the classical primary processes, nucleation and molecular growth, the particle
      size can also increase by aggregation. The special case of self-assembled
      aggregation leads to the formation of highly ordered particles which often
      possess a porous internal structure. In the experiments of these studies the
      particle formation of barium sulfate has been investigated. SEM analysis shows a
      large variety of growth forms including plate-like, star-like, and spherical
      particles, whereas TEM exposures reveal the porous internal structure at all
      investigated supersaturation levels. The pore size and the volume fraction can be
      influenced by changing the supersaturation ratio. By means of a fast sampling
      technique in combination with cryo-TEM analysis it has been shown that the
      particles at the early stages of growth shortly after the beginning of nucleation
      consist of many small nanocrystallites which have aggregated in a highly ordered
      manner. The diffraction pattern indicates many small-angle grain boundaries,
      whereas the particles at the end of the precipitation process are
      monocrystalline. This leads to the conclusion that barium sulfate grows according
      to a self-assembled aggregation mechanism followed by a fast recrystallization
      process.

PMID- 14654395
TI  - Static electrification of solid oxide in liquid metal and electrical double layer
      at the interface.
AB  - Static electrification of a solid oxide, say a semiconducting oxide in liquid
      metal, is mainly due to electron transfer between two phases. Excess electrons in
      the liquid metal phase provided by the oxide give rise to an electrical double
      layer at the interface. The electrical double layer may be divided into three
      parts, an immobile inner layer, a compressed diffuse layer, and a flat layer
      extending into the bulk liquid metal. Differential potential analysis and the
      induced emf method were used to measure the potential of the compressed diffuse
      layer and the excess electron density of the flat layer, respectively. Results
      show that most oxides in liquid metals carry positive charges on their surfaces
      and the potentials of the compressed diffuse layer are in the range of 3 to 42
      microV. Such a low potential implies that the diffuse layer is considerably
      compressed. The excess electron densities of the flat layer are on the order of
      10(22) electrons/m(3) of Hg and their contributions to surface charges of oxide
      are in the range of 10(17) to 10(18) charges/m(2) for the oxide/mercury systems
      with a solid density of 0.3 wt% at room temperature.

PMID- 14654396
TI  - Surface modification of calcium hydroxyapatite with pyrophosphoric acid.
AB  - The surface of synthetic colloidal calcium hydroxyapatite
      (Ca(10)(PO(4))(6)(OH)(2); CaHap) was treated with pyrophosphoric acid
      (H(4)P(2)O(7); PP) in acetone and the materials were characterized by XRD,
      thermal analysis, N(2) adsorption, TEM, and FTIR. No remarkable change in XRD
      patterns or in particle morphology by the modification was observed. The
      additional amount of PO(4) of CaHap was increased with an increase in PP
      concentration. The Ca/P molar ratio of CaHap was decreased from 1.62 to 1.35 by
      the modification. IR results indicated that the PP reacts with surface P-OH
      groups of CaHap to form additional surface P-OH groups as follows: surface P
      OH+H(4)P(2)O(7)--> surface P-O-PO(OH)(2) + H(3)PO(4). When the modified CaHap
      with Ca/P molar ratio less than 1.50 was treated at 850 degrees C in air, the
      materials transformed into beta-Ca(3)(PO(4))(2).

PMID- 14654397
TI  - Voltammetric study of sodium hypochlorite using dendrimer-stabilized gold
      nanoparticles.
AB  - Electrochemical activity of dendrimer-stabilized gold nanoparticles on a glassy
      carbon electrode (GCE) was studied by means of cyclic voltammetry of sodium
      hypochlorite. Dendrimer-stabilized gold nanoparticles were deposited onto a
      glassy carbon surface by electrophoresis and the deposition was observed by
      transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy
      (XPS). Both anodic and cathodic peak currents were found to increase after the
      deposition of dendrimer-stabilized gold nanoparticles. In the case of dendrimers
      deposited onto the GCE surface, the magnitude of the current was smaller than for
      dendrimer-stabilized-gold-nanoparticle-modified GCE. This indicates the
      enhancement in the rate of electrolysis due to gold nanoparticles.

PMID- 14654398
TI  - In situ infrared spectroelectrochemical studies of the corrosion of a nickel
      electrode as a function of applied potential in cyanate, thiocyanate, and
      selenocyanate solutions.
AB  - This paper presents the first subtractively normalized interfacial Fourier
      transform infrared spectroscopic (SNIFTIRS) study of the corrosion system Ni/XCN(
      ) (X=O, S, Se), pH 11, [XCN(-)]=0.05 molL(-1), supporting electrolyte 0.1 molL(
      1) KNO(3), for a nickel electrode as a function of applied potential. Cyclic
      voltammograms, in situ infrared spectra, and current-potential data (recorded
      while the infrared spectral acquisition was in progress) were recorded for a
      nickel electrode in a three-electrode thin-layer cell containing the
      pseudohalides OCN(-), SCN(-), or SeCN(-) ions at pH 11 in a supporting
      electrolyte of KNO(3). In general, the data showed that all of the pseudohalide
      ions studied caused corrosion of the nickel electrode by forming the respective
      nickel-pseudohalide complex ion species as the potential was stepped anodically.
      Two of the ions, SCN(-) and SeCN(-), caused surface modifications to the
      electrode which influenced the electrochemical reactions with respect to CO(2)
      formation. The Ni/SeCN(-) system, for instance, exhibited signs of instability
      during the spectroelectrochemical experiment, red-brown coatings observed on the
      electrode caused by the decomposition of the selenocyanate ion to colloidally
      dispersed elemental selenium. The selenium coated the electrode, hence modifying
      the surface and consequently the electrochemistry, by causing the "early"
      appearance of CO(2)-associated IR peaks in SNIFTIRS spectra recorded from the
      electrode system at potentials lower than those for the Ni/OCN(-) system. In
      contrast, CO(2) formation at the electrode surface was not observed in the
      Ni/SCN(-) system, which was likely to have been caused by nickel sulfide
      poisoning of the electrode surface. In the Ni/SCN(-) and Ni/SeCN(-) systems, IR
      spectra also indicated the buildup of Ni(SCN)(2) and Ni(SeCN)(2) salts in the
      thin layer by the appearance of a peak at ca. 2165 cm(-1) at anodic values of the
      applied potential.

PMID- 14654399
TI  - Intrinsic surface reaction equilibrium constants of structurally charged
      amphoteric hydrotalcite-like compounds.
AB  - The relative equations among intrinsic surface reaction equilibrium constants (K
      in 1-pK model, K(a1)(int) and K(a2)(int) in 2-pK model, and *K(Na)(int) and
      *K(Cl)(int) in inert electrolyte chemical binding model), points of zero charge
      (PZC), and structural charge density (sigma(st)) for amphoteric solids with
      structural charge were established to investigate the effects of sigma(st) on
      intrinsic equilibrium constants and PZC. The intrinsic equilibrium constants of
      HTlc with general formulas [(Zn,Mg)(1-x)Al(x)(OH)(2)](Cl,OH)(x) and [Mg(1
      x)(Fe,Al)(x)(OH)(2)](Cl,OH)(x) were evaluated. The following main conclusions
      were obtained. For amphoteric solids with structural charge, a point of zero net
      charge (PZNC) independent of electrolyte concentration (c) exists. A common
      intersection point (CIP) should appear among the acid-base titration curves at
      different c, and the pH at the CIP is pH(PZNC). The pK, pK(a1)(int), and
      pK(a2)(int) may be expressed as a function of pH(PZNC) and sigma(st), and these
      intrinsic equilibrium constants can be directly calculated from pH(PZNC) and
      sigma(st). The inert electrolyte chemical binding does not exist for amphoteric
      surfaces with structural charge. PZNC is not equal to the point of zero net
      proton charge (PZNPC) when sigma(st) not equal 0. pH(PZNC) > pH(PZNPC) when
      sigma(st)>0; pH(PZNC) < pH(PZNPC) when sigma(st)<0; and pH(PZNC) = pH(PZNPC) only
      when sigma(st)=0. With increasing c, the difference between pH(PZNC) and
      pH(PZNPC) decreases; i.e., pH(PZNPC) moves forward to pH(PZNC) with increasing c.
      For the HTlc samples studied, with increasing x, the pH(PZNC) and the pK(a1)(int)
      and pK(a2)(int) decrease, and the pK increases. These results can be explained on
      the basis of the affinity of metal cations for H(+) or OH(-) and the
      electrostatic interaction between the charging surface and H(+) or OH(-).

PMID- 14654400
TI  - Treatment of humic acids with ferric, aluminum, and chromium ions in water.
AB  - The interaction of ferric, aluminum, and chromium ions with humic acids at
      different pH of mixture has been investigated. The concentration of metal ions,
      bound with humic acid is proportional to the concentration of metal ion in water
      solution at pH 3 at low metal ion concentrations. The ratio of the number of
      ferric ions, bound with humic acid, to the number of acidic groups in humic acid
      is more than 1.5 at high ferric ion concentration in solution. That is bound with
      the formation of dimers of ferric ions and their treatment with acidic groups of
      humic acid. The radius of particles formed in the reaction of humic acid with
      ferric ion does not depend on the pH and decreases in the reaction with chromium
      and aluminum ions at pH higher than 4. An increase of metal ion concentration
      leads to the increase of the particle radius at low metal ion concentration
      reaching the constant value at high metal ion concentration and pH 6.1.

PMID- 14654401
TI  - Poly(ethylene oxide)-based surfactants as templates for the synthesis of
      mesoporous silica materials.
AB  - Various mesoporous silica solids were prepared by using poly(ethylene oxide)
      based surfactants as templates in a neutral, fluoride, or moderately acidic
      medium, and their properties examined by different physical techniques.
      Precipitation in an acid or neutral medium provided materials of pore size in
      between those of micropores and mesopores irrespective of the molecular size of
      the surfactant. On the other hand, syntheses in a fluoride-containing medium
      yielded mesoporous materials with pore diameters over the range 36-84 A that
      increased with increasing surfactant size. All materials possessed specific
      surface areas above 650 m(2)g(-1) and high pore volumes-particularly those
      obtained in a fluorinated medium. The conditions used in the syntheses and the
      fact that all produced highly disordered porous materials suggest that their
      mechanism of formation is essentially of the N(0)I(0) neutral type. The materials
      obtained in the presence of fluoride ion, which promote the condensation of
      siliceous species, retain greater amounts of surfactant and exhibit increased
      cross-linking and decreased particle sizes, which results in textural
      mesoporosity.

PMID- 14654402
TI  - Influence of morphology and composition of fumed oxides on changes in their
      structural and adsorptive characteristics on hydrothermal treatment in steam
      phase at different temperatures.
AB  - A series of fumed oxides such as silica, titania, alumina, silica/alumina (SA),
      silica/titania (ST), and alumina/silica/titania (AST), initial and hydrothermally
      treated (HTT) in the steam phase at T(HTT)=150, 250, and 350 degrees C was
      studied by adsorption, AFM, XRD, FTIR, and theoretical methods. Diminution of the
      size of primary particles (corresponding to increasing S(BET)) of initial silica
      and mixed oxides results in enhancement of their structural changes on HTT with
      elevating T(HTT) and increasing density of packing of primary particles in the
      secondary structures. Relative changes in the texture of treated fumed silicas
      are smaller than those of mesoporous silica gels occurring under similar HTT
      conditions. On HTT, aggregates of primary particles and their agglomerates become
      denser but their surface layers become looser because of transfer of silica
      fragments from one particle to another, and the smaller the initial primary
      particles, the greater the relative diminution of the specific surface area
      S(BET) for the same type of primary particle packing in aggregates. Relative
      changes in the pore volume V(p) (or V(BJHd)) on HTT are more complex than that of
      S(BET), as for many samples the V(p) value increases especially at T(HTT)=150
      degrees C. Alumina and titania partially inhibit structural changes on HTT, which
      decrease in the series silica > SA > AST approximately ST.

PMID- 14654403
TI  - Effect of electrostatic, hydrodynamic, and Brownian forces on particle
      trajectories and sieving in normal flow filtration.
AB  - Particle deposition and fouling are critical factors governing the performance of
      microfiltration and ultrafiltration systems. Particle trajectories were evaluated
      by numerical integration of the Langevin equation, accounting for the combined
      effects of electrostatic repulsion, enhanced hydrodynamic drag, and Brownian
      diffusion. In the absence of Brownian forces, particles are unable to enter the
      membrane pores unless the drag associated with the filtration velocity can
      overcome the electrostatic repulsion. Brownian forces significantly alter this
      behavior, allowing some particles to enter the pore even at low filtration
      velocities. The average particle transmission, evaluated from the probability of
      having a particle enter the pore, increases with increasing filtration velocity
      due to the greater hydrodynamic drag force on the particle. These results provide
      important insights into particle behavior in membrane systems.

PMID- 14654404
TI  - Nonflat equilibrium liquid shapes on flat surfaces.
AB  - The hydrostatic pressure in thin liquid layers differs from the pressure in the
      ambient air. This difference is caused by the actions of surface forces and
      capillary pressure. The manifestation of the surface force action is the
      disjoining pressure, which has a very special S-shaped form in the case of
      partial wetting (aqueous thin films and thin films of aqueous electrolyte and
      surfactant solutions, both free films and films on solid substrates). In thin
      flat liquid films the disjoining pressure acts alone and determines their
      thickness. However, if the film surface is curved then both the disjoining and
      the capillary pressures act simultaneously. In the case of partial wetting their
      simultaneous action results in the existence of nonflat equilibrium liquid
      shapes. It is shown that in the case of S-shaped disjoining pressure isotherm
      microdrops, microdepressions, and equilibrium periodic films exist on flat solid
      substrates. Criteria are found for both the existence and the stability of these
      nonflat equilibrium liquid shapes. It is shown that a transition from thick films
      to thinner films can go via intermediate nonflat states, microdepressions and
      periodic films, which both can be more stable than flat films within some range
      of hydrostatic pressure. Experimental investigations of shapes of the predicted
      nonflat layers can open new possibilities of determination of disjoining pressure
      in the range of thickness in which flat films are unstable.

PMID- 14654405
TI  - Prediction of the surface tension of mixed electrolyte solutions based on the
      equation of Patwardhan and Kumar and the fundamental Butler equations.
AB  - The predictive equation of Patwardhan and Kumar for the water activity of mixed
      electrolyte solutions has been used together with the fundamental Butler
      equations to establish a new simple predictive equation for the surface tension
      of mixed electrolyte solutions. This newly proposed equation can provide the
      surface tensions of multicomponent solutions using only the data of the
      corresponding binary subsystems of equal ionic strength. No binary interaction
      parameters are required. The predictive capability of the equation has been
      tested with the experimental data for 26 concentrated multicomponent electrolyte
      solutions at different temperatures and compared with the model of Li et al. Both
      equations agree well with the experimental results of systems examined over
      entire experimental composition ranges, but the new equation generally gives
      better predictions for most 1:1 electrolyte systems examined, and considerable
      improvement in predictions has been achieved for all the mixtures containing 1:2
      and 2:2 electrolytes and for 1:1 electrolyte systems at higher temperatures.

PMID- 14654406
TI  - Effect of fiber orientation on fiber wetting processes.
AB  - The current work incorporates a microscopic study of the effect of fiber
      orientation on the fiber wetting process and flow of liquid droplets along filter
      fibers when subjected to airflow and gravity forces. Glass filter fibers in
      various combinations were oriented at various angles within a plane defined by
      the airflow direction and were supplied with distilled water in aerosol form. The
      behavior and flow of the liquid collected by the fibers were observed and
      measured using a specially developed microscope cell, detailed in the paper. The
      experimental results were compared to a theoretical model developed to describe
      the behavior. The theory and experimental results showed good agreement. The
      developed theory allows an optimum angle to be determined for the internal filter
      fiber structure in the design of wet filters. A sensitivity analysis of the model
      was conducted to determine the most important parameters. This will aid design of
      wet filtration systems such that maximal self-cleaning can be accomplished with
      minimal water use.

PMID- 14654407
TI  - Raman spectroscopic study on the structure of water in aqueous solution of
      zwitterionic surfactants.
AB  - The structure and hydrogen bonding of water in aqueous solutions of various
      surfactants were analyzed using the contours of the O-H stretching in the
      polarized Raman spectra. From the relative intensity of the collective band (C
      value) corresponding to a long-range coupling of the O-H stretching in the
      aqueous surfactant solutions, the number of hydrogen bonds disrupted due to the
      presence of one surfactant molecule (N(corr) value) was evaluated. The N(corr)
      value for decylsulfobetaine was slightly negative, whereas those for ordinary
      ionic surfactants such as sodium dodecylsulfate and dodecyltrimethylammonium
      chloride were large positive values. Furthermore, the N(corr) for carboxybetaine
      surfactant was a small positive value. These results suggest that zwitterionic
      surfactants do not disturb the hydrogen-bonded network structure of water
      significantly, probably due to the counteraction of the electrostriction effect
      by the proximity between the anionic and cationic groups.

PMID- 14654408
TI  - Cloud point of aqueous solutions containing oxyethylated methyl dodecanoates:
      effects of surfactant hydrophilicity, nature of added electrolyte, and water
      activity.
AB  - The aim of this work was to determine the cloud points of new oxyethylated methyl
      dodecanoates of various hydrophilicity (OMD-n, where n refers to the average
      degree of oxyethylation) and to correlate them with surfactant hydrophilicity
      and, for a given electrolyte, with water activity. Thus, it is shown that the
      cloud point in the absence of electrolyte (CP(0)) can be simulated by the
      following equation: CP(0)=165.5logn-112.0 (with R(2)=0.987). The effects of NaCl,
      NaHCO(3), and KSCN on the cloud point are also reported and discussed. The
      salting-out effect arising from the presence of NaCl or NaHCO(3) is explained by
      the existence of a hydration shell with enhanced water structure as well as a
      zone with decreased salt concentration around the -(OCH(2)CH(2))(n)- chain, as
      compared with the bulk. On the other hand, the salting-in effect is explained by
      depletion of water around the -(OCH(2)CH(2))(n)- chain. Thus, it is estimated
      that the number b of water molecules forced back into the bulk solution from the
      salt-deficient regions when the hydration shells of two -O-CH(2)-CH(2)- monomer
      units overlap ranges between 2 and 3 and 3 and 4 for NaCl and NaHCO(3),
      respectively, depending on the average degree of oxyethylation n of OMD-n. It is
      also shown that the water activity is a useful parameter to simulate the
      variation of cloud point in the presence of an electrolyte (CP) at low and
      moderate concentration (e.g., <1 M NaCl), CP(0)/CP approximately 1
      (bR/alpha)lna(w), where R is the gas constant and alpha approximately 15 JK(
      1)mol(-1). At high electrolyte concentration, the relationship between CP(0)/CP
      and lna(w) significantly deviates from linearity. In the particular case of KSCN,
      an inversion of the salt effect can be observed. The salting-in effect of KSCN
      increases up to about 2 M, but decreases at higher KSCN concentrations, so that
      KSCN can even act as a salting-out salt at high concentration (typically above
      3.3 M for OMD-14).

PMID- 14654409
TI  - Polyoxometalates matrixed into surfactants: synthesis, characterizations, and
      conformations of surfactants.
AB  - We synthesized two surfactant-encapsulated polyoxometalate (POM) clusters (SECs),
      (DODA)(15)[H(3)Mo(57)V(6)(NO)(6)O(189)(H(2)O)(12)(VO)(6)].13H(2)O (SEC-2, DODA:
      dimethyldioctadecyl ammonium) and (DODA)(12)[Eu(H(2)O)P(5)W(30)O(110)].28H(2)O
      (SEC-3). SECs were characterized in detail by elemental analysis, UV-Vis
      absorption spectroscopy, FTIR, 1H NMR, thermogravimetric analysis, Langmuir
      isotherms, and powdered X-ray diffractions. SEC-2 can form a stable monolayer at
      the air-water interface. SEC-2 and SEC-3 possess a layered structure with
      periodicities of 3.8 and 5.05 nm, respectively. Alkyl chains in SEC-2 are
      disordered, but SEC-3 is indicative of well-ordered alkyl chains. According to
      the simplified structural analysis for SEC-2 and SEC-3, DODAs occupy areas of
      1.12 and 0.589 nm(2) on the surface of the POMs, which are characteristic of the
      liquid-like and crystalline-like phases for DODA, respectively. The different
      conformations of DODAs then lead to the different packing structures of SECs.
      This work is aiming to control the organizational structures of the POM-based
      materials by selecting the appropriate POMs.

PMID- 14654410
TI  - Conductometric and spectrofluorimetric characterization of the mixed micelles
      constituted by dodecyltrimethylammonium bromide and a tricyclic antidepressant
      drug in aqueous solution.
AB  - Conductivity and static fluorescence measurements have been carried out at 25
      degrees C to study the monomeric and micellar phases of aqueous solutions of
      mixed micelles constituted by a conventional cationic surfactant,
      dodecyltrimethylammonium bromide (D(12)TAB), and a tricyclic antidepressant drug,
      amitriptyline hydrochloride (AMYTP), with aggregation properties. From
      conductivity data, the total mixed critical micelle concentration and the
      dissociation degree of the mixed micelle have been obtained, while fluorescence
      experiments allow for the determination of the total aggregation number, and the
      micropolarity of micellar inside. Furthermore, the partial contribution of each
      surfactant to the mixed micellization process, through their critical micelle
      concentrations and their aggregation numbers have been determined, as well. The
      solubilization of the drug in the mixed micelles has been also studied through
      the mass action model, by determining the association constant between the
      micelles and the drug. From these results, the use of the micelles studied in
      this work as potential models for vectors of antidepressant drugs of the
      amitriptyline family has been discussed. The theoretical aspects of the mixed
      micellization process have been also analyzed.

PMID- 14654411
TI  - Analysis of rotation-driven electrokinetic flow in microscale gap regions of
      rotating disk systems.
AB  - In the present study, a novel theoretical model is developed for the analysis of
      rotating thermal-fluid flow characteristics in the presence of electrokinetic
      effects in the microscale gap region between two parallel disks under specified
      electrostatic, rotational, and thermal boundary conditions. The major flow
      configuration considered is a rotor-stator disk system. Axisymmetric Navier
      Stokes equations with consideration of electric body force stemming from
      streaming potential are employed in the momentum balance. Variations of the fluid
      viscosity and permittivity with the local fluid temperature are considered.
      Between two disks, the axial distribution of the electric potential is determined
      by the Poisson equation with the concentration distributions of positive and
      negative ions obtained from Nernst-Planck equations for convection-diffusion of
      the ions in the flow field. Effects of disk rotation and electrostatic and
      thermal conditions on the electrokinetic flow and thermal characteristics are
      investigated. The electrohydrodynamic mechanisms are addressed with an
      interpretation of the coupling nature of the electric and flow fields. Finally,
      solutions with electric potential determined by employing nonlinear or linearized
      Poisson-Boltzmann equation and/or invoking assumptions of constant properties are
      compared with the predictions of the present model for justification of various
      levels of approximation in solution of the electrothermal flow behaviors in
      rotating microfluidic systems.

PMID- 14654412
TI  - Solvent effects on amphotericin B monolayers.
AB  - Monolayers of the antifungal antibiotic amphotericin B undergo the liquid
      expanded/liquid condensed state transition if spread from chloroform/methanol
      solvent. The transition disappeared after a long spreading time. The presence of
      the transition may be due to the retention of solvent and/or the presence of
      metastable aggregates of amphotericin B.

PMID- 14654413
TI  - Spatially resolved microrheology through a liquid/liquid interface.
AB  - We present a light-scattering technique for the measurement of the
      microrheological properties of viscoelastic liquids in small volumes over a large
      frequency range (on the order of eight decades). The accuracy of the method for
      model viscoelastic liquids (polyethylene oxide solutions in water) is
      demonstrated by comparing the results with conventional mechanical measurements
      of the loss and storage moduli. Then we show that the method can be used to
      measure variations in viscoelastic properties in a heterogeneous system by
      measuring the variation in the moduli with position (and time) across a
      liquid/liquid interface between a viscoelastic polymer solution and a Newtonian
      liquid.

PMID- 14654414
TI  - Re: An audit of out of hours interventional vascular radiology.

PMID- 14654415
TI  - Re: arguments regarding the 'all autogenous' vascular access policy.

PMID- 14654416
TI  - Prosthetic grafts equal autogenous fistulas only when surgeons ignore reports in
      the literature.

PMID- 14654417
TI  - Re: Role of superficial venous surgery in patients with combined superficial and
      segmental deep venous reflux.

PMID- 14654419
TI  - Results of the principal results and secondary analysis from the European and
      North American randomised trials of endarterectomy for symptomatic carotid
      stenosis.

PMID- 14654420
TI  - Re: The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity
      ulcers: a double-blind randomised-controlled trial.

PMID- 14654422
TI  - Psychiatric comorbidity in patients with epilepsy: implications for diagnosis and
      treatment.
AB  - Psychiatric disorders frequently occur in patients with epilepsy but the
      diagnosis is frequently missed and therapeutic opportunities are often lost.
      These comorbidities assume greater importance as epidemiological data show their
      frequent association with impaired function and quality of life, and advances in
      neurobiology better define their pathophysiological relationship and therapies.
      Epilepsy presents a model for understanding psychiatric illness. Deciphering the
      role of different biological and environmental risk factors may help identify
      high-risk patients and allow for early intervention. Antiepileptic drugs are
      frequently used to manage psychiatric syndromes although the mechanisms of their
      psychotropic action remain uncertain. As recognition and treatment of comorbid
      psychiatric disorders in epilepsy remain suboptimal, we need to increase the
      awareness of physicians, patients, their caregivers, and the health care system.
      Better recognition will help to develop and implement appropriate diagnostic and
      treatment programs, and improve functional outcomes and quality of life in people
      with epilepsy.

PMID- 14654423
TI  - Depression in epilepsy: a frequently neglected multifaceted disorder.
AB  - Depressive disorders (DDs) are frequent psychiatric comorbidities of neurological
      disorders like multiple sclerosis, stroke, dementia, migraine, Parkinson's
      disease, and epilepsy. The clinical manifestations of DDs in these neurological
      disorders are identical to those of idiopathic mood disorders. In epilepsy,
      however, DDs can frequently also present with clinical characteristics that
      differ from those of idiopathic depression and fail to meet the criteria included
      in the Diagnostic and Statistical Manual of Psychiatric Disorders-Fourth Edition.
      Despite their multifaceted clinical expressions and their relatively high
      prevalence in epilepsy, DDs very often go unrecognized and untreated. The aim of
      this article is to review some of the more relevant aspects of DDs in epilepsy,
      to highlight their various clinical expressions, and their impact on the quality
      of life of patients with epilepsy, and to review the basic principles of
      treatment.

PMID- 14654424
TI  - Epilepsy and anxiety.
AB  - Studies in the general population demonstrate that anxiety disorders are
      associated with impaired quality of life and function. Available evidence
      suggests that comorbid anxiety disorders are frequent among patients with
      epilepsy but that neither the interrelationships between them nor the impact of
      anxiety disorders on functional outcome is well studied. The study and management
      of anxiety disorders are further complicated by the occurrence of seizures, the
      temporal relationship between seizures and anxiety symptoms/syndromes, and the
      influence of antiepileptic drugs. Increased recognition of anxiety disorders
      among patients with epilepsy and evaluation of the potential impact of these
      disorders on functional outcome and the beneficial and detrimental effects of
      antiepileptic drugs in clinical practice are needed.

PMID- 14654425
TI  - Psychiatric comorbidity, health, and function in epilepsy.
AB  - Epilepsy is a chronic condition that has complex effects on social, vocational,
      and psychological function. Several psychiatric disorders have been shown to have
      increased prevalence in persons with epilepsy compared to the general population.
      Depression appears to be the most common psychiatric comorbidity, but anxiety and
      other diagnoses have not been extensively investigated. Several studies have
      found that depression or psychological distress may be the strongest predictors
      of health-related quality of life, even including seizure frequency and severity,
      employment, or driving status. Despite the high prevalence and adverse effects of
      comorbid psychiatric disorders in epilepsy, very little is known about optimal
      treatment strategies, or even the efficacy of standard treatments. Further
      research is needed to increase understanding of the mechanisms of psychiatric
      illness in epilepsy, the effects of depression and anxiety on long-term clinical
      outcomes, and the most effective treatments.

PMID- 14654426
TI  - Metabolic engineering of the astaxanthin-biosynthetic pathway of
      Xanthophyllomyces dendrorhous.
AB  - This review describes the different approaches that have been used to manipulate
      and improve carotenoid production in Xanthophyllomyces dendrorhous. The red yeast
      X. dendrorhous (formerly known as Phaffia rhodozyma) is one of the
      microbiological production systems for natural astaxanthin. Astaxanthin is
      applied in food and feed industry and can be used as a nutraceutical because of
      its strong antioxidant properties. However, the production levels of astaxanthin
      in wild-type isolates are rather low. To increase the astaxanthin content in X.
      dendrorhous, cultivation protocols have been optimized and astaxanthin
      hyperproducing mutants have been obtained by screening of classically mutagenized
      X. dendrorhous strains. The knowledge about the regulation of carotenogenesis in
      X. dendrorhous is still limited in comparison to that in other carotenogenic
      fungi. The X. dendrorhous carotenogenic genes have been cloned and a X.
      dendrorhous transformation system has been developed. These tools allowed the
      directed genetic modification of the astaxanthin pathway in X. dendrorhous. The
      crtYB gene, encoding the bifunctional enzyme phytoene synthase/lycopene cyclase,
      was inactivated by insertion of a vector by single and double cross-over events,
      indicating that it is possible to generate specific carotenoid-biosynthetic
      mutants. Additionally, overexpression of crtYB resulted in the accumulation of
      beta-carotene and echinone, which indicates that the oxygenation reactions are
      rate-limiting in these recombinant strains. Furthermore, overexpression of the
      phytoene desaturase-encoding gene (crtI) showed an increase in monocyclic
      carotenoids such as torulene and HDCO (3-hydroxy-3',4'-didehydro-beta,-psi
      carotene-4-one) and a decrease in bicyclic carotenoids such as echinone, beta
      carotene and astaxanthin.

PMID- 14654427
TI  - Phylogenetic circumscription of Saccharomyces, Kluyveromyces and other members of
      the Saccharomycetaceae, and the proposal of the new genera Lachancea,
      Nakaseomyces, Naumovia, Vanderwaltozyma and Zygotorulaspora.
AB  - Genera currently assigned to the Saccharomycetaceae have been defined from
      phenotype, but this classification does not fully correspond with species
      groupings determined from phylogenetic analysis of gene sequences. The multigene
      sequence analysis of Kurtzman and Robnett [FEMS Yeast Res. 3 (2003) 417-432]
      resolved the family Saccharomycetaceae into 11 well-supported clades. In the
      present study, the taxonomy of the Saccharomyctaceae is evaluated from the
      perspective of the multigene sequence analysis, which has resulted in
      reassignment of some species among currently accepted genera, and the proposal of
      the following five new genera: Lachancea, Nakaseomyces, Naumovia, Vanderwaltozyma
      and Zygotorulaspora.

PMID- 14654428
TI  - Variability of HXT2 at the protein and gene level among the Saccharomyces sensu
      stricto group.
AB  - Variability of HXT2 at the protein and gene level was investigated among
      Saccharomyces sensu stricto and other yeast species. Results showed that the HXT2
      gene is probably present in yeast genera other than Saccharomyces, suggesting
      that this gene is widely distributed in the yeast world. Chromosomal analyses
      indicated the stable location of HXT2 on the same chromosome and with the same
      copy number throughout the entire sensu stricto group. Results of the
      immunoblotting assay demonstrated that all strains tested (with the exception of
      S. cerevisiae DBVPG 6042) exhibited a lower level of Hxt2p expression than that
      shown by laboratory wild-type. Moreover, Hxt2p expression seems to reinforce the
      taxonomical differences between the two pairs of species (S. cerevisiae and S.
      paradoxus vs. S. pastorianus and S. bayanus) within the sensu stricto group of
      the genus of Saccharomyces that also reflect their different ecological niche.

PMID- 14654429
TI  - The D1/D2 domain of the large-subunit rDNA of the yeast species Clavispora
      lusitaniae is unusually polymorphic.
AB  - Ten different versions of the D1/D2 divergent domain of the large-subunit
      ribosomal DNA were identified among interbreeding members of the yeast species
      Clavispora lusitaniae. One major polymorphism, located in a 90-bp structural
      motif of the D2 domain, exists in two versions that differ by 32 base
      substitutions. Three other polymorphisms consist of a two-base substitution, a
      two-base deletion, and a single-base deletion, respectively. The polymorphisms
      are independent of one another and of the two mating types, indicating that the
      strains studied belong to a single, sexually active Mendelian population. Several
      strains were heterogeneous for one or more of the polymorphisms, and one strain
      was found to be automictic and capable of producing asci on its own by isogamous
      conjugation or by bud-parent autogamy. These observations suggest circumspection
      in the use of sequence divergence as the principal criterion for delimiting yeast
      species.

PMID- 14654430
TI  - Comparative genotyping of the Saccharomyces cerevisiae laboratory strains S288C
      and CEN.PK113-7D using oligonucleotide microarrays.
AB  - To analyse the reliability and accuracy of genotype analysis with high-density
      oligonucleotide microarrays, this method and other experimental approaches were
      used to analyse genomic DNA of two popular Saccharomyces cerevisiae laboratory
      strains. S288C was used for systematic sequencing of 'the' S. cerevisiae genome;
      CEN.PK113-7D is a popular strain for physiological studies and functional
      genomics. Random amplified polymorphic DNA, electrophoretic karyotyping and
      microarray analysis all indicated a high level of sequence similarity between the
      two strains. In the microarray analysis, as few as 288 (4.5%) of the ca. 6300
      represented yeast genes were identified that yielded significantly different
      hybridisation intensities between the two strains. These could be classified as
      amplified, absent, or with sequence polymorphism in CEN.PK113-7D compared to
      S288C. A detailed analysis focused on the subset of 25 genes called absent in
      CEN.PK113-7D. Among these absent genes, 17 were clustered together on five
      chromosomes, mainly in subtelomeric regions. Thorough analysis of these regions
      by polymerase chain reaction (PCR) and restriction fragment length polymorphism
      confirmed the absence of these genes in CEN.PK113-7D. Surprisingly, three of
      these regions were not smaller in CEN.PK113-7D chromosomes, indicating that they
      may harbour unidentified and potentially new sequences. In addition, eight genes
      called absent by the microarrays were scattered over the chromosomes. Using
      diagnostic PCR most of these genes were actually found to be present in CEN.PK113
      7D, but after sequencing were found to differ significantly at the DNA level from
      S288C, explaining the poor hybridisation to the arrays. Our results indicate that
      DNA microarrays are a powerful tool for determining genotypic similarity between
      different yeast strains. However, to obtain meaningful information at the
      individual gene level, this method should be backed up by additional techniques.

PMID- 14654431
TI  - Yeast communities associated with stingless bees.
AB  - The yeast communities associated with the stingless bees Tetragonisca angustula,
      Melipona quadrifasciata and Frieseomelitta varia were studied. The bees T.
      angustula and F. varia showed a strong association with the yeast Starmerella
      meliponinorum. M. quadrifasciata more frequently carried a species related to
      Candida apicola, but also vectored low numbers of S. meliponinorum. Some of the
      yeasts isolated from adult bees were typical of species known to occur in
      flowers. Other yeast species found in adult bees were more typical of those found
      in the phylloplane. S. meliponinorum and the species in the C. apicola complex,
      also part of the Starmerella clade, may have a mutualistic relationship with the
      bees studied. Many yeasts in that group are often found in bees or substrates
      visited by bees, suggesting that a mutually beneficial interaction exists between
      them.

PMID- 14654432
TI  - Aerobic sugar metabolism in the spoilage yeast Zygosaccharomyces bailii.
AB  - Despite the importance of some Zygosaccharomyces species as agents causing
      spoilage of food, the carbon and energy metabolism of most of them is yet largely
      unknown. This is the case with Zygosaccharomyces bailii. In this study the
      occurrence of the Crabtree effect in the petite-negative yeast Z. bailii ATCC
      36947 was investigated. In this yeast the aerobic ethanol production is strictly
      dependent on the carbon source utilised. In glucose-limited continuous cultures a
      very low level of ethanol was produced. In fructose-limited continuous cultures
      ethanol was produced at a higher level and its production increased with the
      dilution rate. As a consequence, on fructose the onset of respiro-fermentative
      metabolism caused a reduction in biomass yield. An immediate aerobic alcoholic
      fermentation in Z. bailii was observed during the transition from sugar
      limitation to sugar excess, both on glucose and on fructose. The analysis of some
      key enzymes of the fermentative metabolism showed a high level of acetyl-CoA
      synthetase in Z. bailii growing on fructose. At high dilution rates, the
      activities of glucose- and fructose-phosphorylating enzymes, as well as of
      pyruvate decarboxylase and alcohol dehydrogenase, were higher in cells during
      growth on fructose than on glucose.

PMID- 14654433
TI  - The Saccharomyces cerevisiae alcohol acetyl transferase gene ATF1 is a target of
      the cAMP/PKA and FGM nutrient-signalling pathways.
AB  - The ATF1-encoded Saccharomyces cerevisiae yeast alcohol acetyl transferase I is
      responsible for the formation of several different volatile acetate esters during
      fermentations. A number of these volatile esters, e.g. ethyl acetate and isoamyl
      acetate, are amongst the most important aroma compounds in fermented beverages
      such as beer and wine. Manipulation of the expression levels of ATF1 in brewing
      yeast strains has a significant effect on the ester profile of beer. Northern
      blot analysis of ATF1 and its closely related homologue, Lg-ATF1, showed that
      these genes were rapidly induced by the addition of glucose to anaerobically
      grown carbon-starved cells. This induction was abolished in a protein kinase A
      (PKA)-attenuated strain, while a PKA-overactive strain showed stronger ATF1
      expression, indicating that the Ras/cAMP/PKA signalling pathway is involved in
      this glucose induction. Furthermore, nitrogen was needed in the growth medium in
      order to maintain ATF1 expression. Long-term activation of ATF1 could also be
      obtained by the addition of the non-metabolisable amino acid homologue beta-L
      alanine, showing that the effect of the nitrogen source did not depend on its
      metabolism. In addition to nutrient regulation, ATF1 and Lg-ATF1 expression
      levels were also affected by heat and ethanol stress. These findings help in the
      understanding of the effect of medium composition on volatile ester synthesis in
      industrial fermentations. In addition, the complex regulation provides new
      insights into the physiological role of Atf1p in yeast.

PMID- 14654434
TI  - Starvation and temperature upshift cause an increase in the enzymatically active
      cell wall-associated glyceraldehyde-3-phosphate dehydrogenase protein in yeast.
AB  - The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase (cwGAPDH)
      activity in Saccharomyces cerevisiae increases (two- to 10-fold, depending on the
      strain) in response to starvation and temperature upshift. Assays using
      transformants carrying pTDH, a yeast centromer derivative plasmid containing the
      Candida albicans TDH3 gene (encoding GAPDH) fused in frame with the yeast SUC2
      coding region for internal invertase, showed that starvation and/or temperature
      upshift result in a similar increase in both cwGAPDH and cell wall-associated
      invertase activities. In addition, this incorporation of GAPDH protein into the
      cell wall in response to stress does not require (i) de novo protein synthesis,
      indicating that preexisting cytosolic enzyme is incorporated into the cell wall,
      (ii) nor the participation of the ubiquitin yeast stress response system, as no
      differences were observed between wild-type and polyubiquitin-depleted
      (Deltaubi4) strains.

PMID- 14654435
TI  - Expression of the Photorhabdus luminescens lux genes (luxA, B, C, D, and E) in
      Saccharomyces cerevisiae.
AB  - The luxA, B, C, D, and E genes from Photorhabdus luminescens were cloned and
      functionally expressed in Saccharomyces cerevisiae to construct a bacterial lux
      based yeast bioreporter capable of autonomous bioluminescence emission. The
      bioreporter was engineered using a series of pBEVY yeast expression vectors that
      allowed for bi-directional constitutive or inducible expression of the individual
      luxA, B, C, and E genes. The luxD gene, encoding the acyl-ACP transferase that
      ultimately supplies the requisite aldehyde substrate for the bioluminescent
      reaction, was fused to a yeast internal ribosomal entry site (IRES) sequence to
      ensure high bi-cistronic expression. Although self-generation of bioluminescence
      was achieved by the bioreporter, the signal was relatively weak and decayed
      rapidly. To overcome this instability, a flavin oxidoreductase gene (frp) from
      Vibrio harveyi was co-expressed to provide sufficient concentrations of the
      FMNH(2) co-factor required for the bioluminescent reaction. Expression of frp
      with the lux genes not only stabilized but also enhanced bioluminescence to
      levels approaching 9.0x10(5) times above background.

PMID- 14654436
TI  - The delivery of ADP/ATP carrier protein to mitochondria probed by fusions with
      green fluorescent protein and beta-galactosidase.
AB  - The import of proteins into mitochondria is an essential process, largely
      investigated in vitro with isolated mitochondria and radioactively labeled
      precursors. In this study, we used intact cells and fusions with genes encoding
      two reporter proteins, green fluorescent protein (GFP) and beta-galactosidase
      (lacZ), to probe the import of the ADP/ATP carrier (AAC). Typical mitochondrial
      fluorescence was observed with AAC-GFP fusions containing at least one complete
      transmembrane loop. This confirms the results of in vitro analysis demonstrating
      that an internal targeting signal was present in each one of the three
      transmembrane loops of the carrier. The fusions of AAC fragments to beta
      galactosidase demonstrated that the targeting signal was capable of delivering
      the reporter molecule to the mitochondrial surface, but not to internalize it to
      a protease-inaccessible location. The delivery to a protease-inaccessible
      location required the presence of more distal sequences present within the third
      (C-terminal) transmembrane loop of the carrier molecule. The results of our study
      provide an alternative for investigation in a natural context of mitochondrial
      protein import in cells when the isolation of intact, functional mitochondria is
      not achievable.

PMID- 14654437
TI  - Further development of the cassette-based pYC plasmid system by incorporation of
      the dominant hph, nat and AUR1-C gene markers and the lacZ reporter system.
AB  - Dominant selection markers encoding hygromycin B phosphotransferase (hph),
      nourseothricin N-acetyltransferase (nat) and a mutant inositol phosphoceramide
      synthase (AUR1-C) were all incorporated into the pYC yeast plasmid vector system,
      thus expanding this system with possible alternatives to the use of G418
      resistance. We found the markers to be of use not only in standard laboratory
      strains of Saccharomyces cerevisiae but also in an industrial strain of S.
      carlsbergensis (syn. of S. pastorianus) brewing yeast as well as in Saccharomyces
      kluyveri. As the pYC system contains means of counter-selection for plasmid loss
      and loop-out of integrated plasmids, it now provides ample opportunities for
      genetic manipulation of industrial and non-conventional yeasts when the URA3
      marker and FOA counter-selection is not an option. Furthermore, the lacZ system
      for analyzing gene expression was included in the system.

PMID- 14654438
TI  - Construction of a Trp- commercial baker's yeast strain by using food-safe-grade
      dominant drug resistance cassettes.
AB  - We have designed a food-safe-grade module for gene disruptions in commercial
      baker's yeast strains, which contains the G418 resistance cassette, KanMX4,
      flanked by direct repeats from the MEL1 gene of Saccharomyces cerevisiae. This
      module was used to obtain a Trp(-) auxotrophic mutant of the polyploid HY strain
      by successive targeting to the TRP1 locus and later in vivo excision of the
      kan(r) marker. Southern blot analysis indicated that HY contains five copies of
      the TRP1 gene. However, after four disruption rounds, a strain named HYtrpM(4),
      unable to grow in the absence of tryptophan, was selected. Southern and Northern
      analysis of HYtrpM(4) cells showed that a remaining functional wild-type copy was
      still present, suggesting that the level of phosphoribosylanthranylate isomerase
      activity, resulting from a single copy of TRP1, is too low to sustain growth.
      Accordingly, a high reversion frequency of the Trp(-) phenotype, through gene
      conversion, was found in cells of the mutant strain. Nevertheless, this was not a
      drawback for its use as a recipient strain of heterologous genes. Indeed, YEpACT
      X24 transformants were stable after 25 generations and expressed and secreted
      high levels of active recombinant xylanase. These data indicate that the new Trp(
      ) strain can be used to generate a stable recombinant yeast that fulfils all the
      requirements and market criteria for commercial utilisation.

PMID- 14654439
TI  - Application of the reuseable, KanMX selectable marker to industrial yeast:
      construction and evaluation of heterothallic wine strains of Saccharomyces
      cerevisiae, possessing minimal foreign DNA sequences.
AB  - The characterisation of wine yeasts and the complex metabolic processes
      influencing wine fermentation and the quality of wine might best be achieved by
      exploiting the standard classical and recombinant genetic techniques which have
      been successfully used with laboratory strains. However, application of these
      techniques to industrial strains has been restricted because such strains are
      typically prototrophic and often polyploid. To overcome this problem, we have
      identified commercial wine strains with good mating and sporulation properties
      from which heterothallic derivatives were constructed by disruption of the HO
      gene. Consequently, these haploids are amenable to genetic analysis, whilst
      retaining desirable wine-making properties. The approach used was an adaptation
      of a previously published gene disruption procedure for laboratory yeast and is
      based on the acquisition of geneticin resistance from a removable KanMX marker.
      The present work is the first report of the application of a construct of this
      type to the disruption of the HO gene in wine yeasts that are in common
      commercial use. Most of the 4.9-kb disruption construct was successfully removed
      from the genome of the haploid derivative strains by loop-out of the KanMX marker
      through meiotic recombination. Sequencing of the HO region confirmed the
      reduction of foreign sequences to a 582-bp fragment comprised largely of a single
      direct repeat at the target gene. The removal of the active foreign gene
      (conferring antibiotic resistance) allows the application of other constructs
      based on the KanMX module without the need to resort to other selectable marker
      systems. Laboratory-scale fermentation trials typically showed minimal
      differences between the HO disruptants and the parental wine strains in terms of
      fermentation kinetics and formation of key metabolites.

PMID- 14654441
TI  - Analysis of mutual information content for EEG responses to odor stimulation for
      subjects classified by occupation.
AB  - To investigate the changes of cortico-cortical connectivity during odor
      stimulation of subjects classified by occupation, the mutual information content
      of EEGs was examined for general workers, perfume salespersons and professional
      perfume researchers. Analysis of the averaged-cross mutual information content (A
      CMI) from the EEGs revealed that among the professional perfume researchers
      changes in the A-CMI values during odor stimulation were more apparent in the
      frontal region of the brain, while for the general workers and perfume
      salespersons such changes were more conspicuous in the overall posterior
      temporal, parietal and frontal regions. These results indicate that the brains of
      professional perfume researchers respond to odors mainly in the frontal region,
      reflecting the function of the orbitofrontal cortex (OFC) due to the occupational
      requirement of these subjects to discriminate or identify odors. During odor
      stimulation, the perfume salespersons, although relatively more exposed to odors
      than the general workers, showed similar changes to the general workers. The A
      CMI value is in inverse proportion to psychological preferences of the
      professional perfume researchers and perfume salespersons, though this is not the
      case with the general workers. This result suggests that functional coupling for
      people who are occupationally exposed to odors may be related to psychological
      preference.

PMID- 14654440
TI  - Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely
      diagnosed.
AB  - Articles in the literature on alpha-1 antitrypsin (AAT) deficiency have been
      interpreted as indicating that AAT deficiency is a rare disease that affects
      mainly Caucasians (whites) from northern Europe. In a recent publication on the
      worldwide racial and ethnic distribution of AAT deficiency, new data were
      presented demonstrating that it is also found in various populations of African
      blacks; Arabs and Jews in the Middle East; and Central, Far East, and Southeast
      Asians, as well as whites in Australia, Europe, New Zealand, and North America.
      The new data on the prevalence of AAT deficiency in other major racial groups
      worldwide will affect the standards for the diagnosis of AAT deficiency by the
      medical community, with the realization that is not a rare disease of whites in
      northern Europe and immigrants from these countries in the New World. In a total
      population of 4.4 billion in the 58 countries surveyed, there are at least 116
      million carriers (those with Pi phenotypes PiMS and PiMZ) and 3.4 million with
      deficiency allele combinations (phenotypes PiSS, PiSZ, and PiZZ) for the two most
      prevalent deficiency alleles PiS and PiZ; therefore, the new data suggest that
      AAT deficiency may be one of the most common serious single-locus genetic
      diseases in the world. Particularly important is the unique susceptibility of AAT
      deficient individuals to exposure to chemical and particulate environmental
      agents. Such exposures are known to result in both lung and liver disease as well
      as other adverse health effects.

PMID- 14654442
TI  - Time-intensity ratings of nasal irritation from carbon dioxide.
AB  - In three experiments, subjects tracked intensity of nasal irritation during
      sustained presentation of carbon dioxide in the nose. Experiment 1 showed that:
      (i). functions of peak intensity vs. concentration and latency to first non-zero
      ratings agreed with published literature, thereby supporting the validity of the
      technique; (ii). on average, rated intensity peaked approximately 3-4 s after
      stimulus-onset and began to fall rapidly thereafter; (iii). large and stable
      individual differences in temporal dynamics occurred. Experiment 2 replicated
      experiment 1 with some methodological refinements. In experiment 3, application
      of the technique revealed that the nose regains sensitivity with very brief (300
      500 ms) interruptions in presentation of carbon dioxide. In short: (i). the
      method developed here provides a temporally fine-grained tool to study the time
      course of nasal irritation, and (ii). nasal irritation from carbon dioxide shows
      relatively rapid temporal dynamics.

PMID- 14654443
TI  - No influence of scopolamine hydrobromide on odor detection performance of rats.
AB  - Despite speculation that the muscarinic cholinergic antagonist, scopolamine, may
      influence the olfactory sensitivity of rats, there have been no definitive
      studies on this point to date. In this study, we examined the influence of a
      range of doses of scopolamine hydrobromine (namely, 0.10, 0.125, 0.15 and 0.20
      mg/kg i.p.) on the odor detection performance of 15 adult male Long-Evans rats to
      ethyl acetate. Air-dilution olfactometry and a go/no-go operant signal detection
      task were employed. The drug conditions and a saline control were administered to
      each animal in an order counterbalanced by Latin squares, with 2 day intervals
      interspersed between tests. Scopolamine had no significant influence on odor
      detection performance per se, as measured by percent correct S+ and S- responses
      and a non-parametric signal detection measure of sensitivity. This is in contrast
      to the relatively large effects previously observed in the same test paradigm for
      such drugs as the D-1 agonist SKF 38393 and the D-2 agonist quinpirole. These
      data suggest that scopolamine has no meaningful influence on a well-practiced
      odor detection task.

PMID- 14654444
TI  - Effects of odorants on the hypothalamic-pituitary-adrenal axis and interleukin-6
      (IL-6) and IL-6 receptor mRNA expression in rat hypothalamus after restraint
      stress.
AB  - We recently reported that stress alters interleukin (IL)-6 and IL-6 receptor (IL
      6R) mRNA levels in the hypothalamus. Odorants are reported to exert anti-stress
      effects. The aim of our study was to determine the effects of odorants on IL-6
      and IL-6R mRNA expression in the hypothalamus, using reverse transcriptase
      polymerase chain reaction and on serum levels of adrenocorticotropic hormone
      (ACTH) and corticosterone in rats exposed to stress. Control rats were not
      exposed to stress; test control rats were exposed to 4 h stress then immediately
      killed. In other groups, rats were exposed to the same stress followed by 30 min
      exposure air, dimethoxymethylbenzene (DMMB), or citralva. In the air group, IL-6
      and IL-6R mRNA levels were significantly reduced and serum levels of ACTH and
      corticosterone significantly increased relative to the control. Exposure to DMMB
      significantly augmented IL-6 mRNA expression but restored that of IL-6R mRNA, did
      not change serum corticosterone level relative to that of the air group and
      significantly reduced ACTH. In comparison, citralva restored the expression of IL
      6 and IL-6R mRNAs and significantly increased serum ACTH and corticosterone
      levels. Our results indicate that citralva enhances stress-induced activation of
      the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone (CRH)
      mediated stimulation of IL-6, while DMMB enhances the beneficial action of IL-6
      without affecting CRH.

PMID- 14654445
TI  - Axon mis-targeting in the olfactory bulb during regeneration of olfactory
      neuroepithelium.
AB  - During development, primary olfactory axons typically grow to their
      topographically correct target zone without extensive remodelling. Similarly, in
      adults, new axons arising from the normal turnover of sensory neurons essentially
      project to their target without error. In the present study we have examined axon
      targeting in the olfactory pathway following extensive chemical ablation of the
      olfactory neuroepithelium in the P2-tau:LacZ line of mice. These mice express
      LacZ in the P2 subpopulation of primary olfactory neurons whose axons target
      topographically fixed glomeruli on the medial and lateral surfaces of the
      olfactory bulb. Intraperitoneal injections of dichlobenil selectively destroyed
      the sensory neuroepithelium of the nasal cavity without direct physical insult to
      the olfactory neuron pathway. Primary olfactory neurons regenerated and LacZ
      staining revealed the trajectory of the P2 axons. Rather than project solely to
      their topographically appropriate glomeruli, the regenerating P2 axons now
      terminated in numerous inappropriate glomeruli which were widely dispersed over
      the olfactory bulb. While these errors in targeting were refined over time, there
      was still considerable mis-targeting after four months of regeneration.

PMID- 14654446
TI  - Odor similarity does not influence the time needed for odor processing.
AB  - The brain's link between perception and action involves several steps, which
      include stimulus transduction, neuronal coding of the stimulus, comparison to a
      memory template and choice of an appropriate behavioral response. All of these
      need time, and many studies report that the time needed to compare two stimuli
      correlates inversely with the perceived distance between them. We developed a
      behavioral assay in which we tested the time that a honeybee needs to
      discriminate between odors consisting of mixtures of two components, and included
      both very similar and very different stimuli spanning four log-concentration
      ranges. Bees learned to discriminate all odors, including very similar odors and
      the same odor at different concentrations. Even though discriminating two very
      similar odors appears to be a more difficult task than discriminating two very
      distinct substances, we found that the time needed to make a choice for or
      against an odor was independent of odor similarity. Our data suggest that,
      irrespective of the nature of the olfactory code, the bee olfactory system
      evaluates odor quality after a constant interval. This may ensure that odors are
      only assessed after the olfactory network has optimized its representation.

PMID- 14654447
TI  - Absolute configuration of 2-sec-butyl-4,5-dihydrothiazole in male mouse urine.
AB  - The absolute configuration of 2-sec-butyl-4,5-dihydrothiazole (DHT) in urine of
      adult male mice was determined through chiral trifluoroacetyl derivative
      capillary chromatography by comparing the retention time with synthetic
      standards. (S)-DHT was extracted from fresh urine, while neither (R)-DHT nor the
      racemization of (S)-DHT were detected. We can conclude that DHT in urine
      possesses the S configuration, although we cannot exclude a minor component in
      the R configuration. (S)-DHT was then characterized for binding to the complex of
      major urinary proteins of male mouse urine (MUP) and for a behavioral response,
      the competitive scent marking behavior (countermarking). The binding constant of
      (S)-DHT to MUP (determined by competitive displacement) was 8.2 +/- 0.6 microM
      (mean +/- SD) and was 10.5 +/- 0.6 microM for R-DHT, thus excluding a relevant
      difference in binding. (S)-DHT modified countermarking in a peculiar way. Male
      mice were slow in countermarking urinary spots streaked 2 days earlier and on top
      of which (S)-DHT was added shortly before the test. This response was not seen
      when adding (S)-DHT to freshly streaked urinary spots or to clean paper. Unlike
      (S)-DHT, (R)-DHT prompted countermarking rather than delaying it. We can further
      conclude that (S)-DHT in male mouse urine is an aversive chemosignal for
      countermarking.

PMID- 14654448
TI  - Influences of age and sex on a microencapsulated odor memory test.
AB  - While the influences of such variables as age and sex are well established for
      most standardized tests of odor identification and detection, this is not the
      case for tests of odor memory. In this study, 231 non-smoking men and women,
      ranging in age from 10 to 68 years, were administered a standardized 12-item
      match-to-sample microencapsulated odor memory test (OMT). Anosmics were excluded
      from the study. Each participant was asked to smell a target odorant after its
      release from a microencapsulated odorant pad and then, after a delay interval of
      10, 30 or 60 s, to pick the target from a similarly presented set of four odors,
      three of which were foils. Backward counting by threes was required during the
      delay intervals in an effort to minimize semantic rehearsal. Overall OMT scores
      were higher for women than for men, and decreased, in each sex, as a function of
      age in a manner similar to the age-related decline observed in tests of odor
      identification and detection. Performance did not change as a function of delay
      interval. A significant correlation between the overall OMT test scores and
      scores on the University of Pennsylvania Smell Identification Test was observed
      for women, but not for men, in accord with the notion that women may be more
      likely to employ semantic cues in their strategies to remember odors. The
      findings are discussed in light of the complexities of the construct of odor
      memory.

PMID- 14654449
TI  - Coupling between sensory neurons in the olfactory epithelium.
AB  - Coupling of olfactory sensory neurons (OSNs) in the olfactory epithelium of
      Necturus maculosus was demonstrated by dye-transfer with Lucifer yellow CH;
      however, the incidence of dye-transfer was low. Immunocytochemistry and Western
      blot analysis indicated that connexin 43, a gap junction channel subunit, was
      widely expressed by cells in the olfactory epithelium. Electrical coupling by
      presumptive gap junctions was assessed using electrophysiological recordings,
      heptanol block, tracer-uptake through hemi-junctions, and tracer-injection into
      tissue whole-mounts. Coupling, which involved pairs of OSNs only, was detected in
      approximately 3-10% of the OSN population; there was no evidence that OSNs were
      coupled into extended neural syncitia. These results suggest that coupling of
      OSNs by gap junctions is unlikely to have a general role in olfactory responses
      by mature (odor responsive) OSNs. Instead, the incidence of inter-neuronal
      coupling was small, similar to the fraction of immature OSNs, suggesting a
      possible role of gap junctions in the continual turnover and development of OSNs
      or possibly their senescence.

PMID- 14654450
TI  - Human odor detectability: new methodology used to determine threshold and
      variation.
AB  - Current ambiguity concerning the related issues of optimal means for measurement
      of odor sensitivity and the functional properties of the olfactory system hinders
      progress in basic and applied research on the human sense of smell. To address
      these needs, we selected n-amyl acetate (nAA) as a test odorant and developed a
      methodology in which participants (Ps) receive multiple presentations each
      session of several concentrations. Yes-no responses as to whether odor was
      detected are analyzed using binomial statistics, with the probability that a
      given proportion of yes responses (or greater) would occur by chance alone being
      treated as the inverse of detectability. Over the course of multiple sessions,
      this information is also used to maximize the collection of data in the peri
      threshold region. Surprisingly, data collected over as many as 14 sessions were
      fit well by a single logistic regression model relating probability and
      concentration. Threshold concentrations, defined as those corresponding to a
      probability of 0.05, varied from 7.11 to 167.53 p.p.b. (v/v) for 11 Ps. Our
      approach and findings, if shown to be representative of other combinations of Ps
      and odorants, could accelerate the pace of research in human olfaction by
      providing a comprehensive operational definition of the limit of the olfactory
      system to detect odorant molecules.

PMID- 14654451
TI  - Electrophysiological heterogeneity in a functional subset of mouse taste cells
      during postnatal development.
AB  - Taste cells in adult mammals are functionally heterogeneous as to the expression
      of ion channels. How these adult phenotypes are established during postnatal
      development, however, is not yet clear. We have addressed this issue by studying
      voltage-gated K(+) and Cl(-) currents (I(K) and I(Cl), respectively) in
      developing taste cells of the mouse vallate papilla. I(K) and I(Cl) underlie
      action potential waveform and firing properties, and play an important role in
      taste transduction. By using the patch clamp technique, we analyzed these
      currents in a specific group of cells, called Na/OUT cells and thought to be
      sensory. In adult mice, three different electrophysiological phenotypes of Na/OUT
      cells could be detected: cells with I(K) (K cells); cells with both I(K) and
      I(Cl) (K+Cl cells); and cells with I(Cl) (Cl cells). In contrast, at early
      developmental stages (2-4 postnatal days, PD) there were no Cl cells, which
      appeared at PD 8. Our findings indicate a mechanism that contributes to building
      up the functional heterogeneity of mammalian taste cells during the postnatal
      development.

PMID- 14654452
TI  - Monitoring and the controlled processing of meaning: distinct prefrontal systems.
AB  - Distinct prefrontal regions are specialized for the controlled processing of
      semantic information. We have dissociated components of this system used in
      semantic decision-making across different perceptual conditions. Nineteen
      subjects were presented with auditory word sequences, on which they made semantic
      or syllabic decisions, while neural activity was measured using PET. Contrasting
      the semantic with syllabic tasks, there was activation within left rostral
      prefrontal cortex (RPFC) when the stimuli were presented as clear speech,
      reducing when the stimuli were presented in acoustically degraded form. In
      contrast, activation of the right dorsolateral prefrontal cortex (DLPFC) was
      observed with the degraded stimuli, an effect that inversely correlated with
      accuracy on the task. We have thus demonstrated two prefrontal systems where
      activity is differentially modulated by the "quality" of information held in
      working memory. This dissociation is likely to represent an alteration in the
      type of cognitive operations employed during task performance, where left RPFC is
      activated during extensive semantic elaboration and right DLPFC is recruited as
      the monitoring demands, associated with items held in working memory, increase.
      The function of these separate systems is integrated during the performance of
      verbal problem-solving tasks although they are differentially sensitive to
      stimulus degradation.

PMID- 14654453
TI  - Automatically parcellating the human cerebral cortex.
AB  - We present a technique for automatically assigning a neuroanatomical label to
      each location on a cortical surface model based on probabilistic information
      estimated from a manually labeled training set. This procedure incorporates both
      geometric information derived from the cortical model, and neuroanatomical
      convention, as found in the training set. The result is a complete labeling of
      cortical sulci and gyri. Examples are given from two different training sets
      generated using different neuroanatomical conventions, illustrating the
      flexibility of the algorithm. The technique is shown to be comparable in accuracy
      to manual labeling.

PMID- 14654454
TI  - Neural activity in primate parietal area 7a related to spatial analysis of visual
      mazes.
AB  - Cognitive psychological studies of humans and monkeys solving visual mazes have
      provided evidence that a covert analysis of the maze takes place during periods
      of eye fixation interspersed between saccades, or when mazes are solved without
      eye movements. We investigated the neural basis of this process in posterior
      parietal cortex by recording the activity of single neurons in area 7a during
      maze solution. Monkeys were required to determine from a single point of fixation
      whether a critical path through the maze reached an exit or a blind ending. We
      found that during this process the activity of approximately one in four neurons
      in area 7a was spatially tuned to maze path direction. We obtained evidence that
      path tuning did not reflect a covert saccade plan insofar as the majority of
      neurons active during maze solution were not active on a delayed-saccade control
      task, and the minority that were active on both tasks did not exhibit congruent
      spatial tuning in the two conditions. We also obtained evidence that path tuning
      during maze solution was not due to the locations of visual receptive fields
      mapped outside the behavioral context of maze solution, in that receptive field
      centers and preferred path directions were not spatially aligned. Finally,
      neurons tuned to path direction were not present in area 7a when a naive animal
      viewed the same visual maze stimuli but did not solve them. These data support
      the hypothesis that path tuning in parietal cortex is not due to the lower level
      visual features of the maze stimulus, but rather is associated with maze
      solution, and as such, reflects a cognitive process applied to a complex visual
      stimulus.

PMID- 14654455
TI  - Human auditory cortical dynamics during perception of long acoustic sequences:
      phase tracking of carrier frequency by the auditory steady-state response.
AB  - We recorded human auditory cortical activity during the perception of long,
      changing acoustic signals and analyzed information provided by dynamic neural
      population measures over a large range of time intervals (approximately 24 ms-5
      s). Participants listened to musical scales that were amplitude modulated at a
      rate of 41.5 Hz, generating an ongoing, stimulus-related oscillatory brain
      signal, the auditory steady-state response (aSSR). The aSSR generated energy at
      the amplitude modulation rate that was recorded using magnetoencephalography. As
      in previous work, the timing (phase) of this response varied with stimulus
      carrier frequency over the entire course of minute-long tone sequences ('phase
      tracking' of carrier frequency). The length of the time interval over which phase
      was calculated was systematically varied; significant phase tracking was
      regularly observed at analysis intervals of <50 ms in length. The right auditory
      cortex exhibited better phase tracking performance than the left at analysis
      intervals of 24-240 ms, and frequency dependent phase delays were consistently
      larger than those predicted by cochlear mechanics. Based on these empirical data,
      a model of the neural populations responsible for phase tracking suggests that it
      is produced by a subpopulation ( approximately 25%) of the cells generating the
      aSSR.

PMID- 14654456
TI  - Neuronal representation of response-outcome in the primate prefrontal cortex.
AB  - For flexible control of behaviour, it is important to associate preceding
      behavioural response with its outcome. Since the dorsolateral prefrontal cortex
      (dlPFC) plays a major role in such control, it is likely that this area has a
      neuronal mechanism of coding response-outcome, such as reward/non-reward, based
      on the nature of the behavioural response made immediately before. To test this
      hypothesis, we examined neuronal activity in the dlPFC while monkeys performed a
      variant of the oculomotor delayed-response (ODR) task that had two reward
      conditions. In this task, the correct response was rewarded in half of the trials
      only and the subject could not expect the outcome (reward/non-reward). The
      response was followed by a fixation of 2 s (F2-period). We also employed a
      fixation (FIX) task that required monkeys to fixate on the peripheral target
      only, with two reward conditions that were similar to those in the ODR task. Post
      response activity of a subset of dlPFC neurons was modulated by both the
      direction of the preceding response and its outcome. None of these neurons showed
      directional F2-period activity in the FIX task. These results suggest that a
      subset of dlPFC neurons represent response-outcome (i.e. reward/non-reward
      associated with directional saccade made immediately before).

PMID- 14654457
TI  - MEG tomography of human cortex and brainstem activity in waking and REM sleep
      saccades.
AB  - We recorded the magnetoencephalographic (MEG) signal from three subjects before,
      during and after eye movements cued to a tone, self-paced, awake and during rapid
      eye movement (REM) sleep. During sleep we recorded the MEG signal throughout the
      night together with electroencephalographic (EEG) and electromyographic (EMG)
      channels to construct a hypnogram. While awake, just prior to and during eye
      movements, the expected well time-locked physiological activations were imaged in
      pontine regions, with early 3 s priming. Activity in the frontal eye fields (FEF)
      was identified in the 300 ms before the saccade onset. Visual cortex activation
      occurred 200 ms after saccades. During REM, compared to the eyes closed awake
      condition, activity was higher in supplementary motor area (SMA) and lower in
      inferior parietal and precuneus cortex. Electro-occulographic (EOG) activity just
      prior to REM saccades correlated with bilateral pontine and FEF activity some 250
      400 ms before REM saccade onset, which in turn was preceded 200 ms earlier by
      reciprocal activation of the pons and FEF. An orbitofrontal-amygdalo
      parahippocampal-pontine sequence, possibly related to emotional activation during
      REM sleep, was identified in the last 100 ms leading to the REM saccade, but not
      linked to saccade initiation.

PMID- 14654458
TI  - Reward processing in health and Parkinson's disease: neural organization and
      reorganization.
AB  - It has been suggested that motivational processes mediated by dopaminergic neural
      systems may be relatively spared in Parkinson's disease (PD) and activation of
      these pathways may be of therapeutic relevance. To investigate the behavioural
      and neural correlates of motivation in unmedicated PD patients, we used H(2)(15)O
      positron emission tomography to measure brain activation patterns related to the
      processing of monetary rewards of different magnitudes during a spatial search
      task in PD patients withdrawn from medication, and age-matched healthy controls.
      Both groups showed increased search efficiency with increasing reward, but
      demonstrated different patterns of neuronal activation. In healthy controls
      activity in prefrontal and rhinal cortices, and thalamic activity correlated with
      reward magnitude. In contrast, activity in the cerebellar vermis in PD patients
      increased with increasing reward magnitude, suggesting it was sensitive to
      motivational state. We interpret these relative increases in cerebellar
      activation as evidence for the presence of compensatory neural mechanisms in
      unmedicated PD patients.

PMID- 14654459
TI  - Training-induced recovery of visual motion perception after extrastriate cortical
      damage in the adult cat.
AB  - Unilateral ibotenic acid lesions of the lateral suprasylvian (LS) cortex severely
      impair the ability of cats to integrate local motion signals (measured as
      direction range thresholds) and to extract motion signals from noise (measured as
      motion signal thresholds) in their contra-lesional visual hemifields. These
      deficits were found up to several months after the lesions and were limited to
      thresholds measured with random-dot stimuli, while contrast sensitivity for
      discriminating the direction of motion of sine-wave gratings remained unaffected.
      Our goal was to determine whether deficits of complex motion perception could
      recover and whether the recovery was spontaneous or required retraining. In each
      cat, a single location in the impaired visual hemifield was selected for visual
      retraining, which required the animals to discriminate motion direction using
      random-dot stimuli in which the range of dot directions was varied. Fifteen to 40
      days of intensive retraining led to a gradual, complete recovery of motion
      integration. The recovery was stimulus specific since it did not transfer from
      direction range to motion signal thresholds, and it was largely restricted to the
      visual field locations retrained. Delaying the onset of retraining by several
      days to several months had no significant impact on the extent or rate of
      recovery. Once recovery was achieved, performance remained stable over a period
      of several months. These results suggest that recovery of complex visual motion
      perception after lesions of extrastriate visual cortex is an active process that
      requires extensive, stimulus- and retinotopically-specific visual retraining.

PMID- 14654460
TI  - Neuroanatomy of "hearing voices": a frontotemporal brain structural abnormality
      associated with auditory hallucinations in schizophrenia.
AB  - Auditory hallucinations are a frequent symptom in schizophrenia. While functional
      imaging studies have suggested the association of certain patterns of brain
      activity with sub-syndromes or single symptoms (e.g. positive symptoms such as
      hallucinations), there has been only limited evidence from structural imaging or
      post-mortem studies. In this study, we investigated the relation of local brain
      structural deficits to severity of auditory hallucinations, particularly in
      perisylvian areas previously reported to be involved in auditory hallucinations.
      In order to overcome certain limitations of conventional volumetric methods, we
      used deformation-based morphometry (DBM), a novel automated whole-brain
      morphometric technique, to assess local gray and white matter deficits in
      structural magnetic resonance images of 85 schizophrenia patients. We found
      severity of auditory hallucinations to be significantly correlated (P < 0.001)
      with volume loss in the left transverse temporal gyrus of Heschl (primary
      auditory cortex) and left (inferior) supramarginal gyrus, as well as
      middle/inferior right prefrontal gyri. This demonstrates a pattern of distributed
      structural abnormalities specific for auditory hallucinations and suggests
      hallucination-specific alterations in areas of a frontotemporal network for
      processing auditory information and language.

PMID- 14654461
TI  - Involvement of tumor necrosis factor alpha in hippocampal development and
      function.
AB  - Tumor necrosis factor alpha (TNFalpha) is a cytokine produced mainly by cells of
      the immune system. It is also expressed by brain neurons and glia. The
      physiological role of TNFalpha in the brain is not yet fully clear. Using
      TNFalpha-deficient mice, we have examined its role in hippocampal development and
      function. We report here that TNFalpha is involved in the regulation of
      morphological development in the hippocampus. TNFalpha-deficient mice exhibited
      an accelerated maturation of the dentate gyrus region and smaller dendritic trees
      in CA1 and CA3 regions in young mouse. In addition to its involvement in
      hippocampal morphogenesis, TNFalpha deficiency specifically improved performance
      of affected mice in behavioral tasks related to spatial memory. Moreover, lack of
      TNFalpha increased the expression of nerve growth factor (NGF), but not brain
      derived neurotrophic factor (BDNF), following performance of the learning task.
      Our results suggest that TNFalpha actively influences hippocampal development and
      function. In adult mice, TNFalpha may interfere with memory consolidation,
      perhaps by regulating NGF levels.

PMID- 14654462
TI  - Functional brain mapping of the macaque related to spatial working memory as
      revealed by PET.
AB  - To define the cortical areas that subserve spatial working memory in a nonhuman
      primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and
      positron emission tomography while monkeys performed a visually guided saccade
      (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical
      Parametric Mapping and regions of interest-based analyses revealed an increase of
      rCBF in the area surrounding the principal sulcus (PS), the superior convexity,
      the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex
      (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral
      bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the
      prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values
      correlated positively with ODR task performance scores. From the hippocampus,
      rCBF values correlated negatively with ODR task performance. From the AS,
      superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated
      positively with rCBF values and negatively with hippocampus rCBF values. These
      results suggest that neural circuitry in the prefrontal cortex directly
      contributes the spatial working memory processes and that, in spatial working
      memory processes, the posterior parietal cortex and hippocampus have a different
      role to the prefrontal cortex.

PMID- 14654463
TI  - Honoring Donald L. Morton, MD: Society of Surgical Oncology President, 1992-1993.

PMID- 14654464
TI  - The eternally enigmatic axilla: further controversy about axillary lymph nodes in
      breast cancer.

PMID- 14654465
TI  - Sentinel lymph node biopsy for breast cancer: does anybody not need one?

PMID- 14654466
TI  - Primary and metastatic hepatic carcinoid: is there an algorithm?

PMID- 14654467
TI  - Carcinoma of the ampulla of vater: a distinct disease entity?

PMID- 14654468
TI  - Resecting isolated adrenal metastasis: why and how?

PMID- 14654469
TI  - A nomogram for predicting the likelihood of additional nodal metastases in breast
      cancer patients with a positive sentinel node biopsy.
AB  - BACKGROUND: The standard of care for breast cancer patients with sentinel lymph
      node (SLN) metastases includes complete axillary lymph node dissection (ALND).
      However, many question the need for complete ALND in every patient with
      detectable SLN metastases, particularly those perceived to have a low risk of non
      SLN metastases. Accurate estimates of the likelihood of additional disease in the
      axilla could assist greatly in decision-making regarding further treatment.
      METHODS: Pathological features of the primary tumor and SLN metastases of 702
      patients who underwent complete ALND were assessed with multivariable logistic
      regression to predict the presence of additional disease in the non-SLNs of these
      patients. A nomogram was created using pathological size, tumor type and nuclear
      grade, lymphovascular invasion, multifocality, and estrogen-receptor status of
      the primary tumor; method of detection of SLN metastases; number of positive
      SLNs; and number of negative SLNs. The model was subsequently applied
      prospectively to 373 patients. RESULTS: The nomogram for the retrospective
      population was accurate and discriminating, with an area under the receiver
      operating characteristic (ROC) curve of 0.76. When applied to the prospective
      group, the model accurately predicted likelihood of non-SLN disease (ROC, 0.77).
      CONCLUSIONS: We have developed a user-friendly nomogram that uses information
      commonly available to the surgeon to easily and accurately calculate the
      likelihood of having additional, non-SLN metastases for an individual patient.

PMID- 14654470
TI  - Breast cancer survival according to number of nodes removed.
AB  - BACKGROUND: Results from randomized trials indicate a 5.4% survival advantage
      associated with axillary dissection. To gain insight on survival outcomes when
      less than an axillary dissection is performed, we performed a retrospective
      analysis to determine survival outcome for node-negative and node-positive breast
      cancer patients when a variable number of nodes were excised. METHODS: The data
      analyzed in this paper are from the Surveillance, Epidemiology, and End Results
      (SEER) database, from which 72,102 patients were selected whose breast cancer had
      been diagnosed in 1988 or later and who were aged 40-79 years at diagnosis, had a
      single primary lesion, and had 0 to 3 positive lymph nodes. Cases were separated
      into age groups (40 to 49 and 50 to 79 years), and node-negative cases were
      separated from those with one to three positive nodes. RESULTS: This analysis
      indicates that even when all regional lymph nodes are pathologically negative,
      the number of nodes removed is associated with survival. In the group of breast
      cancer patients who had one to three pathologically positive nodes, as with the
      node-negative group, the higher the number of nodes removed, the greater the
      survival. The hazard rate for death in the node-negative group was roughly 5%
      less for each additional five nodes removed. For the node-positive group, the
      hazard rate for death was between 8% and 9% less for each additional five nodes
      removed. CONCLUSIONS: This retrospective study supports the notion that removal
      of regional nodes, even when such nodes are interpreted as pathologically
      negative, is important for the long-term survival of breast cancer patients.

PMID- 14654471
TI  - Sentinel lymph node metastasis in microinvasive breast cancer.
AB  - BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM) is a separate
      pathological entity, distinct from pure ductal carcinoma in situ (DCIS). DCISM is
      a true invasive breast carcinoma with a well-known metastatic potential.
      Currently, there is controversy regarding the indication for complete axillary
      dissection (CAD) to stage the axilla in patients with DCISM. The role of CAD is
      questioned given its morbidity and reported low incidence of axillary
      involvement. Sentinel lymph node biopsy (SLNB) may obviate the need for CAD in
      these patients without compromising the staging of the axilla and the important
      prognostic information. METHODS: From March 1996 to December 2002, 4602
      consecutive patients with invasive breast carcinoma underwent SLN biopsy. Of
      these, 41 patients with DCISM were selected. RESULTS: Metastasis in the SLN were
      detected in 4 of 41 (9.7%) patients. Two of the 4 patients had only
      micrometastasis in the SLN. In three patients, the SLN was the only positive node
      after CAD. CONCLUSIONS: SLN biopsy should be considered as a standard procedure
      in DCISM patients. SLNB can detect nodal micrometastasis and accurately stage the
      axilla avoiding the morbidity of a CAD. Complete AD may not be mandatory if only
      the SLN contains micrometastatic disease. Informed consent is very important in
      the decision not to undergo CAD.

PMID- 14654472
TI  - Touch preparation or frozen section for intraoperative detection of sentinel
      lymph node metastases from breast cancer.
AB  - BACKGROUND: The preferred technique for intraoperative evaluation of the sentinel
      lymph node has not been determined. The purpose of this study was to compare the
      sensitivity and accuracy of intraoperative evaluation of the sentinel lymph node
      by touch preparation cytology and frozen section. METHODS: A total of 117
      patients with clinically node-negative breast cancer or ductal carcinoma-in-situ
      undergoing sentinel lymph node biopsy had intraoperative evaluation of the
      sentinel node by touch preparation, frozen section, or both. The results of the
      intraoperative evaluation were compared with the final histological results of
      hematoxylin and eosin (H&E) paraffin section and immunohistochemistry (IHC).
      RESULTS: Twenty-six (57%) of the 46 patients with nodal involvement had
      metastases detected during surgery. The sensitivity of touch preparation for
      detecting macrometastases was 78%; for detecting all H&E metastases, including
      micrometastases, was 57%; and for detecting all metastases, including those seen
      on IHC, was 40%. The sensitivity of frozen section for detecting macrometastases
      was 83%; for detecting all H&E metastases, including micrometastases, was 78%;
      and for detecting all metastases, including those seen on IHC, was 64%. Both have
      a low sensitivity for micrometastases seen by H&E paraffin section: 57% and 78%,
      respectively. Neither detected micrometastases diagnosed by IHC only.
      CONCLUSIONS: Both touch preparation and frozen section seem to be accurate in
      detecting macrometastases, but not micrometastases. Intraoperative evaluation of
      the sentinel lymph node by touch preparation allows for a quick evaluation of the
      node without wasting significant tissue and without detecting occult microscopic
      metastases, which may be beneficial because the clinical importance of these has
      yet to be elucidated.

PMID- 14654473
TI  - Long-term survival after resection for primary hepatic carcinoid tumor.
AB  - BACKGROUND: Primary hepatic carcinoid tumors (PHCTs) are extremely rare, and
      fewer than 50 cases have been reported in the English-language literature. We
      report a patient with a PHCT and review the cases in the literature. METHODS: Our
      patient presented with symptoms and underwent liver resection for PHCT and
      regional lymph node metastasis. He underwent two more liver resections over the
      following 7 years for recurrent PHCT. Cases reported in the English-language
      literature were reviewed and survival analysis was performed with the Kaplan
      Meier method. The survival impacts of age, gender, tumor foci, extrahepatic
      metastasis, unilobar versus bilobar disease, and type of preoperative treatment
      were determined by means of log-rank test. RESULTS: Our patient has been free of
      symptoms for 14 years of follow-up and free of disease for 8 years of follow-up.
      Forty-eight cases of PHCT were found in the literature, and 92% of these patients
      underwent resection. Actuarial 5- and 10-year survival for all patients was 78%
      and 59%, respectively, whereas for resected patients, 10-year survival was 68%.
      The administration of preoperative chemotherapy, radiation therapy, or
      chemoembolization did not impact survival, nor did age, gender, presence of
      extrahepatic metastasis, number of tumors, or distribution of the tumor within
      the liver. CONCLUSIONS: Resection is the treatment of choice for PHCT and has
      provided favorable outcomes. Resection for PHCT can be performed in most patients
      and offers long-term survival.

PMID- 14654474
TI  - Patterns and predictors of failure after curative resections of carcinoma of the
      ampulla of Vater.
AB  - BACKGROUND: Curative resection does not always equate with long-term survival.
      The aim was to identify patterns and predictors of failure and independent
      factors of prognosis after curative resection. METHODS: Sixty-six patients with
      ampullary carcinoma who underwent surgical intervention were reviewed. Fifty-nine
      patients underwent pancreaticoduodenectomy. Cox regression analysis, log-rank
      test, Fisher exact test, or chi(2) test was used. RESULTS: No patient died as a
      result of surgery; major complications occurred in three, and the 5-year survival
      rate after curative resection (n = 55) was 52.6%. Significant survival predictors
      were preoperative serum carcinoembryonic antigen level; gross tumor appearance;
      tumor, node, and tumor node metastasis stage; and microscopic lymphatic vessel
      and venous invasion in the primary tumor. Multivariate analysis demonstrated that
      lymphatic vessel invasion, tumor, and tumor node metastasis stage were
      significant independent prognostic factors. No patient experienced locoregional
      failure alone; all 24 relapsed patients had distant failure, and six of them had
      both. The liver was the most frequent metastatic organ, followed by nodes,
      peritoneum, lung, and bone. The carcinoembryonic antigen and carbohydrate antigen
      levels and lymphatic vessel and venous invasion were significant predictors of
      distant failure, and the mean time to relapse was 13 (range, 0.7-33) months.
      CONCLUSIONS: Curative resection is associated with significant survival; however,
      effective systemic adjuvant therapy is needed to prevent distant failure for
      patients with elevated carcinoembryonic antigen and carbohydrate antigen levels
      or positive lymphatic vessel or venous invasion. A 3-year follow-up period would
      be necessary to document relapses.

PMID- 14654475
TI  - Interferon-beta is more potent than interferon-alpha in inhibition of human
      hepatocellular carcinoma cell growth when used alone and in combination with
      anticancer drugs.
AB  - BACKGROUND: The prognosis of advanced hepatocellular carcinoma (HCC) is extremely
      poor, but promising effects of chemotherapies combined with interferon (IFN) have
      been reported. METHODS: To develop more effective combination therapies for HCC,
      we compared the antiproliferative effects of IFN-alpha and IFN-beta in
      combination with various cytotoxic drugs on hepatoma cell lines using MTT assay
      and isobologram analysis. RESULTS: IFN-beta was more potent than IFN-alpha in
      inhibiting the cell growth of all cell lines (P <.05, two-way ANOVA). PLC/PRF/5
      was more sensitive to either IFN, than HLE and HuH7. Cell growth of all cell
      lines was inhibited in a dose-dependent manner by 5-fluorouracil (5-FU),
      cisplatin (CDDP), and doxorubicin (DOX), but the sensitivities of these cells
      were considerably different. As for IFN-alpha, synergistic effects were observed
      when combined with 5-FU and DOX on PLC/PRF/5 cells only, whereas IFN-beta showed
      synergistic effects with 5-FU and CDDP on HuH7 and PLC/PRF/5 cell lines.
      CONCLUSION: The spectra of the antiproliferative activity and synergistic effect
      of IFN-beta when combined with anticancer drugs are more potent than those of IFN
      alpha. Combinations of IFN-beta and anticancer drugs may provide a better
      treatment of HCC when combinations with IFN-alpha are ineffective.

PMID- 14654476
TI  - Metastasis to the adrenal gland: the emerging role of laparoscopic surgery.
AB  - BACKGROUND: It is unclear whether resection of clinically isolated metastasis to
      the adrenal gland improves survival. Also, the role of laparoscopic adrenalectomy
      (LA) for metastasis is controversial. This study aimed to (1) identify patients
      who are most likely to have prolonged survival after resection of adrenal
      metastasis and (2) compare oncological outcomes of LA and open adrenalectomy
      (OA). METHODS: A retrospective review of 41 patients, who underwent either OA or
      LA for metastasis to the adrenal gland during 1997-2002 at a single institution,
      was conducted. RESULTS: There were 20 women and 21 men, with a median age of 59
      years. The most common disease was non-small-cell lung carcinoma (n = 23),
      followed by renal cell carcinoma (n = 6). With a median follow-up of 16 months,
      the overall five-year actuarial survival was 29% (median, 28 months). Four
      patients were actually alive at four years after adrenalectomy. Disease-free
      interval (DFI) > 6 months was the only significant predictor of improved
      survival. LA was performed for 11 patients. There was no difference in the
      incidence of positive resection-margins or survival between patients with OA or
      LA. CONCLUSIONS: Adrenalectomy for metastasis, with intent to prolong survival,
      should be offered to patients with favorable tumor biology, such as those with
      significant DFI. The oncological outcome from LA appears similar to that from OA.

PMID- 14654477
TI  - The real impact and usefulness of video-assisted thoracoscopic surgery in the
      diagnosis and therapy of clinical lymphadenopathies of the mediastinum.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of video-assisted
      thoracoscopic surgery (VATS) in the diagnosis and therapy of clinical mediastinal
      lymphadenopathies. METHODS: In our Institute, from 1995 to 2001, 85 patients
      underwent VATS biopsy: 55 subjects (group 1) for suspected lung cancer (65%) and
      30 (group 2) for unknown nodes enlargement (35%). Lymphonodes were considered
      suspected if > 1 cm by radiological imaging. We performed 83 thoracoscopic
      biopsies: 33 in level 5 (39%), 24 in level 6 (29%), 19 in level 7 (22%), and 7 in
      level 8 (8%). RESULTS: A histological analysis of frozen sections was made in
      every case. Twenty subjects underwent lung resection in one-time (24%). Histology
      in group 1 was adenocarcinoma in 28 cases, epidermoid carcinoma in 14,
      microcytoma in 9, and giant-cell carcinoma in 4. Ten patients were at stage I, 10
      at stage II, 33 at stage III, and two at stage IV. Histology of group 2 was
      lymphoma in 18 cases, sarcoidosis in eight, and focal aspecific hyperplasia in
      four. CONCLUSION: The usefulness of VATS allowed the pathological assessment of
      the presumed involved mediastinal lymph nodes in every patient and thus permitted
      to assure in all the cases the indicated therapeutic treatment.

PMID- 14654480
TI  - Digital image processing: a primer for JVIR authors and readers: Part 3: Digital
      image editing.
AB  - This is the final installment of a three-part series on digital image processing
      intended to prepare authors for online submission of manuscripts. In the first
      two articles of the series, the fundamentals of digital image architecture were
      reviewed and methods of importing images to the computer desktop were described.
      In this article, techniques are presented for editing images in preparation for
      online submission. A step-by-step guide to basic editing with use of Adobe
      Photoshop is provided and the ethical implications of this activity are explored.

PMID- 14654481
TI  - In Memoriam: Ethel Jean Finck, MD: 1932-2003.

PMID- 14654482
TI  - Catheter-directed thrombolytic therapy for limb ischemia: current status and
      controversies.
AB  - Absence of urokinase from the United States market for the past 4 years has
      resulted in increasing experience with other plasminogen activators in catheter
      directed thrombolytic therapy. The differences in the pharmacologic properties
      and biologic behavior of these agents may translate into clinical outcomes that
      are distinct. Some of these manifestations can be predicted based on the existing
      large clinical trials in the acute myocardial infarction literature. However,
      because of the fundamental differences in techniques and thrombolytic regimens,
      extrapolation of the coronary data may not always predict the performance of
      these agents in peripheral catheter-directed fibrinolysis. In this article, the
      current status of the available lytic agents in the treatment of limb ischemia is
      reviewed.

PMID- 14654483
TI  - Superselective microcoil embolization for the treatment of lower gastrointestinal
      hemorrhage.
AB  - PURPOSE: To evaluate the safety and effectiveness of superselective microcoil
      embolization for the treatment of lower gastrointestinal (LGI) hemorrhage.
      MATERIALS AND METHODS: A retrospective review of LGI superselective microcoil
      embolization data for a 10-year period was performed. During this period, twenty
      two patients with evidence on angiography of LGI bleeding underwent
      superselective microcoil embolization. Hemorrhage was treated in the colon (n =
      19) and jejunum (n = 3). Ivalon was used adjunctively in two patients and gelfoam
      was used as a secondary agent in two additional patients. Postembolization
      ischemia was evaluated objectively in 14 patients by colonoscopy (n = 10),
      surgical specimen (n = 3), and barium enema (n = 1). All patients were followed
      for clinical evidence of bowel ischemia. Four patients died before further follow
      up could be performed. Additionally, 122 cases of LGI hemorrhage treated with
      superselective microcoil embolization were identified in a review of the
      literature. A meta-analysis was then performed, combining the data in this study
      and the data from the literature, to estimate the rate of major and minor
      ischemic complications on a total of 144 superselective microcoil embolizations.
      RESULTS: Immediate hemostasis was achieved in all 22 patients in this study.
      Complete clinical success was achieved in 86% of patients (19 of 22 patients).
      Rebleeding occurred in 14% of patients (3 of 22 patients) and each underwent
      colonoscopic intervention with success. Postembolization objective follow-up was
      performed in 64% of patients (14 of 22 patients). Ten patients underwent follow
      up colonoscopy; one patient received a follow-up barium enema; and three patients
      underwent subsequent surgery. Colonic resection (one partial and one total) was
      performed in two patients. The partial colectomy was performed in a patient who
      had been diagnosed with colonic polyps and dysplasia. The total colectomy was
      performed on a patient with history of chronic LGI bleeding complicated by long
      term anticoagulation therapy and a history of tubular adenoma resection. The
      third surgical patient (16 months old) underwent a follow-up exploratory
      laparotomy after embolization of a proximal jejunal branch of the superior
      mesenteric artery. None of the three patients who underwent surgery were found to
      have postembolic ischemic changes in the bowel specimen. Four patients in this
      study died, for reasons unrelated to hemorrhage or embolization, before further
      follow-up could be performed. The last four patients were followed clinically and
      experienced no symptoms of intestinal ischemia. A minor ischemic complication was
      reported in 4.5% of patients (1 of 22 patients), and there were no major ischemic
      complications (0%) in this series. A review of the data from 122 cases of LGI
      superselective microcoil embolization in the literature is also presented.
      Combined with the data in this study, the minor complication rate was 9% (13 of
      144 patients), and the major complication rate was 0% (0 of 144 patients).
      CONCLUSION: Superselective microcoil embolization is a safe and effective
      treatment for LGI hemorrhage.

PMID- 14654484
TI  - Use of rheolytic thrombectomy in treatment of acute massive pulmonary embolism.
AB  - PURPOSE: The 6-F Xpeedior (AngioJet; Possis Medical, Minneapolis, MN) rheolytic
      thrombectomy catheter (RTC) uses high velocity saline jets for thrombus
      aspiration, maceration, and evacuation, through the Bernoulli principle. The
      purpose of this study was to evaluate the efficacy of thrombus removal using the
      RTC in patients with acute massive pulmonary embolism (PE). MATERIALS AND
      METHODS: Seventeen patients (mean age, 51.7 + 16.6 years; range, 30-86 years; 9
      men, 8 women) with massive PE initially diagnosed by computed tomography (CT) or
      VQ scan and confirmed by pulmonary angiography were treated with the RTC. All
      patients had acute onset of PE symptoms and all presented with hemodynamic
      compromise and dyspnea. Ten of 17 patients had enough residual thrombus to
      warrant adjuvant catheter directed thrombolytic infusion with reteplase. Six
      patients had contraindications to thrombolytic therapy. One patient presented
      with renal cell carcinoma and tumor embolus as suspected cause of PE.
      Angiographic and clinical outcomes during the hospital stay were evaluated.
      RESULTS: The RTC was successfully delivered and operated via a 0.035-inch guide
      wire in all attempted cases. Treatment resulted in immediate angiographic
      improvement and initial relief of PE symptoms (improvement in dyspnea and oxygen
      saturation) in 16 of 17 patients. One patient developed heart block during the
      procedure, and further treatment with the RTC was discontinued. Bradycardia
      occurred in one patient (managed with lidocaine). After thrombectomy, 10 patients
      received adjunctive reteplase thrombolysis for treatment of residual thrombus,
      and 12 received inferior vena cava (IVC) filters. In the patient with renal cell
      carcinoma, histopathologic analysis of the evacuated material confirmed tumor
      origin of the embolism. There were two deaths, both within 24 hours of treatment
      and secondary to PE. One death occurred in a patient who had only minimal
      thrombus removal after treatment with the RTC and no thrombolysis. The remaining
      15 patients showed continued improvement in PE symptoms and were eventually
      discharged from the hospital with mean length of stay 10.3 + 6.5 days (range, 5
      30 days). CONCLUSIONS: Rheolytic thrombectomy can be performed effectively in
      patients with massive PE. However, a large portion of the patients in this study
      underwent adjuvant overnight thrombolytic infusion. Further evaluation in a
      larger cohort of patients is warranted to assess whether this treatment may offer
      an alternative or complement to thrombolysis or surgical thrombectomy.

PMID- 14654485
TI  - Gelatin sponge closure device versus manual compression after peripheral arterial
      catheterization procedures.
AB  - PURPOSE: To evaluate the safety and efficacy of the QuickSeal system, which
      delivers an over-the-wire extravascular porcine gelatin sponge (nonbovine and
      noncollagen), compared with manual compression in a single interventional
      radiology practice. MATERIALS AND METHODS: This single-institution report
      involves 141 patients undergoing peripheral diagnostic and interventional
      procedures in a teaching and private-practice setting. A 3:2 device-to-control
      ratio was used with randomization stratified by type of procedure, interventional
      or diagnostic. Primary endpoints included time to hemostasis (TTH), time to
      ambulation (TTA), and rate of major complications. Sheaths were removed in the
      device group when activated clotting times (ACTs) were < or =300 seconds for
      patients without glycoprotein (GP) IIb/IIIa platelet inhibitors and < or =250
      seconds for patients with GP IIb/IIIa platelet inhibitors. Sheaths were removed
      in the control group when ACTs were < or =180 seconds. RESULTS: The mean TTH was
      significantly shorter (P <.001) in the device group (8.2 minutes) than in the
      control group (14.12 minutes). Mean TTA was shorter in the device group (2.7
      hours) than in the control group (7.1 hours), and the time to discharge was
      shorter in the device group (23.8 hours) than in the control group (43.6 hours).
      There were no major complications in either group, and the incidences of minor
      complications were not significantly different. CONCLUSION: The tested device
      reduced TTH, TTA, and eligibility for hospital discharge while maintaining a
      safety profile equivalent to that of manual compression in diagnostic and
      interventional procedures.

PMID- 14654487
TI  - Malignant tracheobronchial strictures: palliation with covered retrievable
      expandable nitinol stent.
AB  - PURPOSE: To evaluate the safety and clinical effectiveness of a covered
      retrievable expandable nitinol stent for the treatment of malignant
      tracheobronchial stricture and/or esophagorespiratory fistula (ERF). MATERIALS
      AND METHODS: With fluoroscopic guidance, stents were placed in 35 symptomatic
      patients with malignant tracheobronchial stricture and/or ERF in most cases
      caused by lung or esophageal cancer. The site of stricture was most commonly at
      the trachea or left main bronchus. If there were complications, the stent was
      removed with a retrieval set. Nine patients had combined symptomatic ERF.
      RESULTS: A total of 47 tracheobronchial stents were placed and were technically
      successful and well-tolerated in all patients. Improvement of dyspnea was
      achieved in 92% of the patients (24 of 26 patients). Associated ERF in nine
      patients was effectively treated with tracheobronchial stent placement with or
      without esophageal stent placement. Stent migration, tumor overgrowth,
      symptomatic sputum retention, and hemoptysis occurred in 17% (6/35), 6% (2/35),
      20% (7/35), and 17% (6/35) of patients, respectively. There were no documented
      cases of tumor ingrowth. Stent removal was performed easily in five patients when
      stent migration (n = 2), severe pain (n = 1), tumor overgrowth (n = 1), or
      persistent gastrobronchial fistula (n = 1) developed. All patients died 2 days to
      26 weeks (mean, 9.62 weeks) after stent placement because of disease progression
      (n = 18), pneumonia (n = 9), hemoptysis (n = 5), or unknown cause (n = 3).
      CONCLUSION: Use of a covered retrievable expandable nitinol stent is a safe and
      effective method for relieving dyspnea. This procedure contributed to improved
      quality of life for patients with malignant tracheobronchial stricture and/or
      ERF. Stent retrievability was useful in resolving stent-related complications.

PMID- 14654488
TI  - Cholangitis and liver abscess after percutaneous ablation therapy for liver
      tumors: incidence and risk factors.
AB  - PURPOSE: To determine the risk factors of cholangitis and liver abscess occurring
      after percutaneous ablation therapy for liver tumors. MATERIALS AND METHODS:
      Between October 1995 and September 2002, 358 patients with 455 liver tumors
      underwent a total of 683 ablation procedures, such as percutaneous ethanol
      injection (PEI), percutaneous microwave coagulation (PMC), and radiofrequency
      (RF) ablation therapy. With a retrospective review of medical records, the rates
      and outcomes of cholangitis and/or liver abscess occurring after ablation therapy
      were evaluated. The relationship between cholangitis and/or liver abscess and
      multiple variables (age, disease, Child-Pugh class, size of nodules, multiplicity
      of nodules, history of transcatheter arterial embolization, presence of
      bilioenteric anastomosis, and lack of prophylactic antibiotics administration)
      were statistically analyzed. RESULTS: Cholangitis and/or liver abscess occurred
      in 10 sessions (1.5%) in 10 patients: six sessions after PEI, three sessions
      after PMC, and one session after RF ablation. Both cholangitis and liver abscess
      were noted in seven sessions, cholangitis was noted in two, and liver abscess was
      noted in one. Six patients recovered, but two developed recurrent cholangitis and
      liver abscess, one developed lung abscess complicated with liver abscess, and one
      died of septic shock associated with cholangitis. On stepwise regression
      analysis, bilioenteric anastomosis was the sole significant predictor of
      cholangitis and/or liver abscess formation (P <.001; odds ratio = 36.4; 95% CI =
      9.67-136.9). CONCLUSION: Bilioenteric anastomosis strongly correlated with the
      development of cholangitis and/or liver abscess after percutaneous ablation
      therapy. Close posttreatment attention should be paid to this subgroup of
      patients.

PMID- 14654489
TI  - Percutaneous extrahepatic portacaval shunt with covered prostheses: feasibility
      study.
AB  - PURPOSE: To assess the anatomic feasibility of creating a percutaneous
      extrahepatic portosystemic shunt (PEPS) between the main portal vein (MPV) and
      the inferior vena cava (IVC) in patients with cirrhosis and to evaluate the
      feasibility of this approach in an animal model. MATERIALS AND METHODS: In human
      studies, computed tomographic (CT) scans from 34 patients with cirrhosis were
      reviewed to assess the distance and anatomic structures found between the MPV and
      IVC. The MPV was divided into upper, middle, and lower thirds for analysis. In
      the experimental model, PEPS were created in 10 beagle dogs by placing between
      the MPV and IVC a tubular polyurethane-covered prosthesis with flared ends
      designed for this study. Different approaches, devices, and prostheses were
      assayed. RESULTS: In human studies, the shortest mean distance between the IVC
      and the MPV was found in the lower third of the MPV (1.18 cm +/- 0.6). The lower
      third, the nearest to the confluence of splenic and superior mesenteric veins,
      also presented fewer intervening structures, and the spatial relationship between
      the veins at this level was predictable. In the experimental model, direct
      portography was performed, with a small mesenteric vein catheterized through a
      minilaparotomy and a transjugular access to the IVC. A needle was advanced from
      the MPV to the IVC, and a polyurethane cone-shaped covered prosthesis was placed
      to bridge the path between the veins. Six of 10 animals died from bleeding that
      occurred either because several punctures were made during the procedure or
      because the prosthesis became dislodged when the mesentery was moved before
      suturing the minilaparotomy. The remaining four were kept alive for 1, 5, 60, and
      90 days after the procedure. CONCLUSIONS: PEPS creation in patients with
      cirrhosis is anatomically possible. The lower third of the MPV should be the most
      suitable level at which to create the shunt. Preliminary studies carried out in
      beagle dogs support the feasibility of this approach. However, further work is
      needed to improve the efficacy of this technique.

PMID- 14654490
TI  - Changes in ultrasonographic echogenicity and visibility of needles with changes
      in angles of insonation.
AB  - PURPOSE: To objectively compare the echogenicity of several types of needles at
      clinically important angles of insonation. MATERIALS AND METHODS: Four commercial
      needles (Echotip, Mini-Stick, Echo-Coat, Surflo) and a prototype dimpled needle
      were tested in a liver phantom at angles of insonation ranging from 90 degrees to
      15 degrees. Photodensity measurement determined echogenicity levels in arbitrary
      echogenicity units (EU). RESULTS: At 90 degrees angles of insonation all needles
      were easily seen (60-76 EU) and echogenic levels were similar (P =.264). All
      values decreased with angulation. From the 35 degrees to 15 degrees angles, the
      prototype and Echotip needles were superior (P <.05). At 15 degrees the values
      were 43 EU for the prototype needle, 40 EU for the Echotip needle, 9.0 EU for the
      Echo-Coat needle, and 5.0 EU for the Surflo needle. CONCLUSION: With angulation,
      all needles drop in echogenicity, with prototype dimpled and Echotip best
      maintaining visibility at clinically important angles.

PMID- 14654491
TI  - Changing trends in gynecologists' opinions of uterine artery embolization for
      fibroids: the patient's perspective.
AB  - This study's purpose was to survey patients' perceptions of gynecologists'
      opinions of uterine artery embolization (UAE) for fibroids. Twenty-one women who
      underwent UAE between July 2000 and April 2002 and 21 women who underwent UAE
      between September 1998 and July 2000 completed questionnaires. Each woman was
      asked what her gynecologist's initial opinion was toward UAE, what treatment
      options were offered, who initiated discussion of UAE, and whether she returned
      to the same gynecologist after UAE. As of 2002, more gynecologists had a
      favorable opinion of UAE and were offering UAE versus in the year 2000. The
      majority of patients whose gynecologists initially opposed UAE did not return to
      the same gynecologists, reflecting a similar trend noted 2 years earlier.

PMID- 14654493
TI  - Translumbar high inferior vena cava access placement in patients with thrombosed
      inferior vena cava filters.
AB  - Venous access is a dire necessity in some patients such as those with end-stage
      renal disease or short gut syndrome. The right internal jugular vein is the
      preferred entry site for tunneled central venous catheters. Alternatively, the
      left internal jugular is considered next, with the external jugular and
      subclavian veins being considered later. Catheter-related venous stenosis
      approaches 40% in certain sites, resulting in loss of access sites. As sites are
      lost, insertion of functional long-term central venous catheters becomes
      challenging. Translumbar inferior vena cava (IVC) access created in two patients
      with limited venous access sites who had thrombosed IVCs containing IVC filters
      is described. Because of the higher IVC punctures in these cases, procedural
      planning with cross-sectional imaging is crucial to avoid puncturing the right
      renal artery as it passes posterior to the IVC.

PMID- 14654496
TI  - Recurrent bronchobiliary fistula: unsuccessful management with repeated insertion
      of metallic biliary stent.
AB  - This case of a recurrent bronchobiliary fistula was first managed temporarily
      with repeated metallic biliary stent placement, and finally required surgery. A
      65-year-old man, who had undergone a hepatic resection for metastatic colon
      carcinoma, with a bronchobiliary fistula was treated with metallic biliary stent
      placement for a stenosis in the common bile duct. During 16 months of follow-up,
      the biliptysis recurred twice by a recurrent stricture of the common bile duct,
      which was managed by placement of a second and third stent in a coaxial manner.
      Three months after placement of the third stent, jaundice developed and the
      patient finally underwent a Roux-en-Y choledochojejunostomy.

PMID- 14654495
TI  - Remote thermometry to avoid complications in radiofrequency ablation.
AB  - Percutaneous image-guided radiofrequency ablation (RFA) of tumors has the
      potential risk for thermal damage to nearby normal collateral tissues. Thus, the
      goal of creating a sufficient area of tumor necrosis must be weighed against the
      risk for injury to collateral tissues. In this study, remote thermistors were
      used to monitor temperatures near collateral structures during tumor RFA. Four
      unique cases are described. When temperature-sensitive structures are near the
      target lesion, remote thermometry could further increase the safety of this
      evolving minimally invasive procedure.

PMID- 14654497
TI  - Enterobiliary fistula after radiofrequency ablation of liver metastases.
AB  - A 46-year-old man underwent radiofrequency (RF) ablation of three liver
      metastases 7 months after undergoing right colectomy for a pT2N0Mx colon
      adenocarcinoma. Three months after the procedure, he developed hepatic abscesses
      related to a fistula between the distal ileum and segment V biliary branches.

PMID- 14654498
TI  - Metastatic involvement of a retrieved inferior vena cava filter.

PMID- 14654499
TI  - The European Smoking Prevention Framework Approach (ESFA): short-term effects.
AB  - The European Smoking Prevention Framework Approach (ESFA) resulted in a smoking
      prevention project for six European countries. It included activities on four
      levels: adolescents, schools, parents and out-of-school activities. Common goals
      and objectives were developed, but countries were also able to include additional
      objectives. National diversities required country-specific methods. The most
      important common element was a school-based programme consisting of at least five
      lessons paying attention to social influence processes and training in refusal
      skills. During the first year, significantly more smoking prevention activities
      were realized in experimental schools compared with control schools. Not all
      countries had the same number of lessons on resisting peer pressures. Significant
      cognitive changes were observed in Spain, resulting in more negative attitudes,
      increased self-efficacy levels and a more negative intention towards smoking in
      the experimental group. Counter-productive cognitive effects were observed in the
      UK. Significantly less onset of weekly smoking in experimental groups was found
      in Finland (4.7%) and Spain (3.1%). Counter-productive effects were observed in
      Denmark and the UK. In conclusion, while having common objectives, the ESFA
      approach allowed for a great deal of diversity. Fundamental research using
      dismantling designs is needed to be able to detect the most effective elements of
      smoking prevention programmes for different age groups. Attention to parenting
      styles and practices is also needed.

PMID- 14654501
TI  - Evaluation of a Health Promoting Schools program to reduce smoking in Australian
      secondary schools.
AB  - This randomized controlled trial evaluated the effectiveness of a multicomponent
      Health Promoting Schools (HPS) intervention program in improving self-reported
      smoking outcomes among a cohort of adolescents in 22 public secondary schools in
      the Hunter Region of New South Wales, Australia. Pre-test surveys were completed
      by students in the first 2 years of secondary school, with a 2-year post-test
      survey. Multivariate analyses examined intervention effect for the main outcome,
      post-test smoking behavior, controlling for pre-test smoking status, school and
      other confounders. The sample comprised the cohort of 1852 students who completed
      both surveys. The results demonstrated that the HPS program failed to improve
      smoking behavior over the 2 years (equal increase of 10% in both groups). The
      program was successful in improving smoking knowledge, but not attitudes, in
      intervention versus control group (P < 0.001). Independent predictors of post
      test smoking included: pre-test smoking [odds ratio (OR) = 5.44; 95% confidence
      interval (CI) = 3.20-9.28], being female (OR = 0.55; CI = 0.35-0.87), having more
      close friends who smoked (OR = 1.42; CI = 1.33-1.52), peer group having no clear
      opinion about smoking (OR = 3.23; CI = 1.27-8.27), having more positive and less
      negative attitudes towards smoking, and being less involved in school activities.
      We discuss methodological issues in multicomponent community-based interventions,
      and highlight the strengths and limitations of this study.

PMID- 14654502
TI  - Are precontemplators less likely to change their dietary behavior? A prospective
      analysis.
AB  - The association between baseline stage of change and intervention outcomes is
      examined in a sample of African-American adults who participated in the Eat for
      Life Trial, a study to increase fruit and vegetable (F & V) intake conducted
      through Black churches. We explore whether precontemplators responded differently
      over time than those in the preparation stage, a group assumed to be more likely
      to change their behavior. Stage of change, F & V intake (by food-frequency
      questionnaires) and psychosocial variables were assessed at baseline and 1-year
      follow-up. Individuals initially classified as precontemplators reported an
      increase in F & V intake as large as those in the preparation stage and
      precontemplators' post-test intake was equivalent to those in preparation.
      Precontemplators' change in psychosocial outcomes was also as large or larger
      than those in the preparation stage. At least with regard to F & V, these
      findings raise questions regarding the validity of stage of change, one element
      of the Transtheoretical Model, as a predictor of future behavior and intervention
      response.

PMID- 14654503
TI  - 'If I let a goal in, I'll get beat up': contradictions in masculinity, sport and
      health.
AB  - This paper presents a critical exploration of the relationship between
      masculinity, sport and health by reporting findings from a wider qualitative
      study on lay men's and health professionals' beliefs about masculinity and
      preventative health care. Recent years have seen a surge of interest in relation
      to 'men's health'. In particular, the Department of Health has highlighted how
      men's connection to sport, fitness and competitiveness can be used in health
      promotion initiatives to introduce facets of health. In contrast, work in the
      sociological and feminist literature has raised issues of concern about the
      relationship between men, masculinity and sport, particularly the links to
      aggression, misogyny and homophobia. It would appear then that a straightforward
      'men + sport = health' relationship cannot be assumed. Focus groups and
      interviews with health professionals and men, including gay and disabled men,
      were undertaken to facilitate examination of the socially integrative meanings of
      sport and masculinity, and their relationship to health. Socializing, 'macho'
      culture and the body emerged as three main themes, and the implications of these
      empirical findings for health promotion are discussed.

PMID- 14654504
TI  - Multi-agency, multi-professional work: experiences from a drug prevention
      project.
AB  - Policy documents at local, national and international level continue to call for
      greater multi-agency and multi-professional working. These calls are based on
      three arguments: (1) health and illness are created and influenced by multiple
      factors outside of health service policy, (2) health improvement requires
      collaboration between statutory, voluntary and private sector organizations, and
      (3) efficiency and effectiveness are aided when duplication of effect is avoided
      and service transition is as seamless as possible. However, there remains limited
      process-orientated research that has explored the difficulties and challenges
      faced during multi-agency and multi-professional work. This study employed
      qualitative methods (interviews, participant observation and documentary
      analysis) to understand the social construction of a multi-agency and multi
      professional health promotion project orientated toward the prevention of drug
      related harm. The findings illustrate the ways in which the processes involved in
      securing funding led to multiple and competing project aims, how changes in
      personnel and the internal (re)organization of agencies created disjunctions in
      project membership and shared understandings of key priorities, and how the
      social need to keep group members 'onside' and committed, competed with the
      imperatives of prioritization and addressing issues surrounding differentials in
      power between members and between agencies.

PMID- 14654505
TI  - A systematic review of school drug education.
AB  - This paper provides an up-to-date systematic review of the school drug education
      literature (to June 2001) and identifies components that have the potential for
      creating effective drug education programmes in schools. This paper is a summary
      of a 150-page review. The review adopts a well-defined search methodology,
      specific selection criteria, and has made a series of recommendations based on
      the findings of past reviews and recent primary studies that met the selection
      criteria. The review is inclusive of reviews and recent primary studies that
      involved young people in school settings that encompassed a classroom
      intervention, included drug-related behavioural measures and had a positive
      impact on students' drug-related behaviours. The review identifies several areas
      that should be the focus of future programmes. These include timing and
      programming issues, content and delivery issues, teacher training, and
      dissemination. There is much refinement that can occur in school drug education
      implementation and research. The way forward is to continue to create and test
      interventions that bring together all components of the development,
      implementation and evaluation of school drug education that are effective in
      creating behaviour change, and that are practical to the school setting.

PMID- 14654506
TI  - What influences elderly peoples' decisions about whether to accept the influenza
      vaccination? A qualitative study.
AB  - Influenza and its related illnesses remain a major cause of preventable morbidity
      and mortality in the elderly worldwide. The current influenza vaccine campaign in
      the UK is only a partial success despite annual costly publicity campaigns. The
      aim of this study was to explore the influences on decision making by elderly
      people for influenza vaccine uptake. Twenty patients age 75 years and over were
      purposively selected from those eligible for influenza vaccination in an inner
      city general practice in England. In-depth qualitative interviews were conducted
      with 10 patients who accepted and 10 who refused the vaccine. Those interviewed
      were concerned about maintaining their health, and had a good understanding of
      influenza, its transmission and prevention. The decision whether to accept or
      refuse the influenza vaccination was influenced by trust or mistrust of modern
      medicine, prior experience of vaccination and perceived risk from influenza.
      Newly acquired lay experience and personal perceived risk from influenza seemed
      to be more important catalysts for the change in vaccination uptake than
      professional recommendation or advertising by official government health
      agencies. In order to improve uptake rates, the official message promoting
      vaccine uptake needs to take more account of lay knowledge and the subjective
      assessment of risk.

PMID- 14654507
TI  - Organizational capacity and implementation change: a comparative case study of
      heart health promotion in Ontario public health agencies.
AB  - This paper reports the results of a comparative case study that examines factors
      influencing changes in implementation of heart health promotion activities in
      Ontario public health units. The study compared two cases that experienced large
      changes in implementation from 1994 to 1996, but in opposite directions. Multiple
      data sources were used, with an emphasis on secondary analyses of quantitative
      surveys of health units and other community agencies, and in-depth interviews of
      public health staff, collected as part of the Canadian Heart Health Initiative
      Ontario Project. Guided by social ecological and organizational theories, changes
      in implementation were explained by examining changes in (1) organizational
      predisposition to undertake heart health promotion activities, (2) organizational
      practices to undertake these activities, (3) other internal organizational
      factors and (4) external system factors. Findings show that in communities with
      diverse characteristics, implementation change was most strongly influenced by an
      interplay of changes in internal features of public health agencies; notably,
      leadership, structure and staff skills. Findings support a social ecological
      approach to health promotion by demonstrating the importance of the institutional
      context in the implementation change process, the interaction of individual
      (skills) and organizational (structure) levels in explaining implementation
      change, and community context in shaping the change process. Findings also
      reinforce the value of strengthening capacity within public health agencies and
      suggest further research on the implementation change process, especially in
      different systems and over longer periods of time.

PMID- 14654508
TI  - Social participation and health in a community rich in stock of social capital.
AB  - In Finland, members of the Swedish-speaking minority, many of whom live in the
      province of Ostrobothnia, intermingle with the Finnish-speaking majority.
      Although the two language communities are quite similar to each other in most
      societal respects, including socioeconomic status, education and use of health
      services, significant disparities have been reported in the morbidity, disability
      and mortality between the Swedish-speaking minority and the Finnish-speaking
      majority. Since the population genetic, ecological and socioeconomic
      circumstances are equal, Swedish speakers' longer active life is difficult to
      explain by conventional health-related risk factors. A great deal of health
      inequality (between the language groups) seems to derive from uneven distribution
      of social capital, i.e. the Swedish-speaking community holds a higher amount of
      social capital that is associated with their well-being and health. Factor
      analysis revealed four patterns of social capital measures, i.e. voluntary
      associational activity, friendship network, religious involvement and hobby club
      activity, of which associational activity, friendship network and religious
      involvement were significantly associated with good self-rated health. Also,
      trustful friendship network, hobby club activity and religious involvement as
      well as avoidance of intoxication-prone drinking behavior were significantly more
      frequent among the individuals of the Swedish-speaking community. We suggest that
      health promotion should seek ways of working which would encourage social
      participation.

PMID- 14654511
TI  - Measuring health in a vacuum: examining the disability weight of the DALY.
AB  - The Disability Adjusted Life Year (DALY) is a widely used summary measure of
      population health combining years of life lost due to mortality and years of
      healthy life lost due to disability. A feature of the DALY is that, in the
      assessment of morbidity, each health condition is associated with a disability
      weight. The disability weight lies on a scale between 0 (indicating the health
      condition is equivalent to full health) and 1 (indicating the health condition is
      equivalent to death). The disability weight associated with each health condition
      is currently fixed across all social, cultural and environmental contexts. Thus
      blindness in the United Kingdom has the same disability weight as blindness in
      Niger in spite of structural interventions in the UK that make the disability
      less severe than in Niger. Although the fixed disability weight is defended on
      grounds that it supports a strongly egalitarian flavour in the DALY, we argue
      that the lack of consideration of realistic contexts results in a measure that
      will underestimate the burden associated with morbidity in disadvantaged
      populations and overestimate the burden in advantaged populations. There is,
      consequently, a loss of information on possible non-clinical points of
      intervention. Disaggregated estimates of the burden of disease such as those in
      the World Health Report 2000 should be interpreted with caution.

PMID- 14654512
TI  - Decentralization in Zambia: resource allocation and district performance.
AB  - Zambia implemented an ambitious process of health sector decentralization in the
      mid 1990s. This article presents an assessment of the degree of decentralization,
      called 'decision space', that was allowed to districts in Zambia, and an analysis
      of data on districts available at the national level to assess allocation choices
      made by local authorities and some indicators of the performance of the health
      systems under decentralization. The Zambian officials in health districts had a
      moderate range of choice over expenditures, user fees, contracting, targeting and
      governance. Their choices were quite limited over salaries and allowances and
      they did not have control over additional major sources of revenue, like local
      taxes. The study found that the formula for allocation of government funding
      which was based on population size and hospital beds resulted in relatively equal
      per capita expenditures among districts. Decentralization allowed the districts
      to make decisions on internal allocation of resources and on user fee levels and
      expenditures. General guidelines for the allocation of resources established a
      maximum and minimum percentage to be allocated to district offices, hospitals,
      health centres and communities. Districts tended to exceed the maximum for
      district offices, but the large urban districts and those without public district
      hospitals were not even reaching the minimum for hospital allocations. Wealthier
      and urban districts were more successful in raising revenue through user fees,
      although the proportion of total expenditures that came from user fees was low.
      An analysis of available indicators of performance, such as the utilization of
      health services, immunization coverage and family planning activities, found
      little variation during the period 1995-98 except for a decline in immunization
      coverage, which may have also been affected by changes in donor funding. These
      findings suggest that decentralization may not have had either a positive or
      negative impact on services.

PMID- 14654513
TI  - Using willingness to pay to investigate regressiveness of user fees in health
      facilities in Tanzania.
AB  - The study uses data from the Tanzania Human Resources Development Survey (1994)
      on willingness to pay (WTP) for desired quality of health care at lower-level
      health facilities to assess potential regressiveness of user fees - a
      disproportionately higher negative effect of user fees on utilization of health
      services among the poor compared with the rich. Despite reports of extensive
      bypassing of the lower-level health facilities in Tanzania, the WTP for quality
      health care at these health facilities is surprisingly large. WTP was lower among
      the poor, female and elderly respondents. Almost one-quarter of the poorest 40%
      of the population was not willing to pay even when the quality of services met
      their expectations. The results suggest that: the utilization of health services
      at lower-level health facilities can be increased by improving the quality of
      care; and the implementation of uniform user charges in the public facilities may
      be regressive, adversely affecting utilization among the poor, women and the
      elderly. An effective system of exemptions and waivers will be required for the
      very poor who may not be able to pay even when quality of services is improved.
      The findings of the study have policy implications for the Tanzanian government's
      recent attempts to expand cost-sharing through community health funds at lower
      level health facilities, being introduced since 1998.

PMID- 14654514
TI  - Costs of near-miss obstetric complications for women and their families in Benin
      and Ghana.
AB  - This paper estimates the total cost to women and their families associated with a
      spontaneous vaginal delivery and five types of 'near-miss' obstetric complication
      in Benin and Ghana, and assesses affordability in relation to household cash
      expenditure. A retrospective evaluation of costs was carried out among 121
      mothers in three hospitals in Ghana. A prospective evaluation of costs was
      undertaken among 420 pregnant women in two hospitals in Benin. Information was
      collected on the cost of travel to the facilities and of direct medical and non
      medical costs incurred during their stay in hospital. In Benin, costs ranged from
      an average of 15 US dollars for a spontaneous delivery to 256 US dollars for a
      near-miss complication caused by dystocia. In Ghana, average costs ranged from 18
      US dollars for a spontaneous vaginal delivery to 115 US dollars for a near-miss
      complication caused by haemorrhage. Medical costs accounted for the largest share
      of total costs, mainly drugs and medical supplies in Ghana and costs of the
      delivery and any surgical intervention in Benin. Payments associated with a
      spontaneous vaginal delivery amounted to at least 2% of annual household cash
      expenditure in both countries. In the case of severe obstetric complications,
      costs incurred reached a high of 34% of annual household cash expenditure in
      Benin. The economic burden of hospital-based delivery care in Ghana and Benin is
      likely to deter or delay women's use of health services. Should a woman develop
      severe obstetric complications while in labour, the relatively high costs of
      hospital care could have a potentially catastrophic impact on the household
      budget.

PMID- 14654515
TI  - Community-based antenatal education in  Istanbul, Turkey: effects on health
      behaviours.
AB  - In this article we describe the implementation and evaluation of a community
      based antenatal education programme for first-time expectant mothers carried out
      in  Istanbul, Turkey, as part of the Healthy Beginnings Project. We hypothesized
      that women participating in an antenatal education programme would be more likely
      to have a vaginal birth, practice recommended maternal and infant health-related
      behaviours, and adopt a contraceptive method after the birth than a control
      group, even after statistically controlling for differences in background
      characteristics. Methods used to evaluate the antenatal education programme
      included pre- and post-tests with programme participants and a household survey
      with participants and a control group. All antenatal education course
      participants, as well as a control group composed of women giving birth to their
      first child at the same hospitals, were interviewed in their homes by a trained
      interviewer 2.5-3 months after the baby's birth, starting in October 1998.
      Results of statistical analyses indicate that a community-based antenatal
      education programme, such as the one offered as part of The Healthy Beginnings
      Project in  Istanbul, may increase the chance that women will adopt behaviours
      beneficial to health in the period following a birth. In particular, behaviours
      related to infant health (breastfeeding and infant check-up) and contraception
      appeared to be influenced by participation in the programme. In a developing
      country such as Turkey, with persistent maternal and child health problems, there
      is an urgent need to increase both demand for and quality of reproductive health
      services. Antenatal education is not the only answer, but it can be part of the
      answer. Reaching couples early in their reproductive lives may encourage them to
      adopt healthy behaviours and make use of available services during their
      reproductive years.

PMID- 14654516
TI  - Community participation in externally funded health projects: lessons from
      Cambodia.
AB  - This article provides lessons learned on establishing effective community
      participation in two externally funded, NGO-implemented health projects working
      at district level in Cambodia. The first project was implemented in accordance
      with the Cambodian national guidelines on community participation. The second -
      using lessons and experiences gained as a result of the first project - worked
      with Buddhist pagoda volunteers. Primary research was conducted in both settings
      to assess the effectiveness of the two participation strategies. The article
      concludes that the success of community participation in externally funded health
      projects with relatively short implementation timeframes requires engagement with
      existing community-based organizations and agencies. In Cambodia, where Theravada
      Buddhism is the dominant religion, pagodas and associated volunteers appear to
      represent such an organization. Community participation structured around pagoda
      volunteers - who are held in high esteem within their local communities - is more
      effective and sustainable than newly (and externally) established community
      structures with formally elected representatives. Pagodas and associated
      volunteers in rural Cambodia offer the advantages of effective leadership, local
      organization, resource mobilization and management. It is recommended that
      programmes and agencies wishing to adopt community participation strategies in
      health utilize participatory research to identify the most appropriate local
      organization to lead such initiatives.

PMID- 14654517
TI  - Training outreach workers for AIDS prevention in rural India: is it sustainable?
AB  - Through a process of community diagnosis and participation, a non-governmental
      organization in rural Karnataka state in India selected and trained peer outreach
      workers to implement and sustain AIDS prevention education activities. This
      activity was part of a larger AIDS education project that aimed at creating
      awareness and promoting risk-reducing behaviours in the community. This paper
      describes efforts of the project to identify and train peer educators during its
      implementation phase and discusses strategies used to facilitate sustainability.
      We evaluate the impact of these efforts by conducting an analysis in the project
      area 2 years after the end of the project. The findings reveal generalized
      interest among rural communities in HIV prevention issues. The project originally
      conducted an extensive survey to understand community organization and
      composition, which helped to identify potential partners and peer educators.
      Training peer educators was a multi-step process, and one with high attrition.
      While individual peer educators were an excellent resource during the life of the
      project, peer educators affiliated with village level institutions had the
      interest, access to resources and willingness to sustain project efforts.
      However, the sustainability of their efforts was associated with the quality of
      interactions with the project implementation team, the strength and leadership of
      their own institutions, the perceived benefits of implementing AIDS education
      activities after project life and the gender of the outreach worker. Non
      sustainers did not have an organizational structure to backstop their work, were
      often poor and unemployed persons who later found gainful employment, and
      overwhelmingly, were female. We present a conceptual model based on these
      findings to help future projects plan for and achieve sustainability.

PMID- 14654518
TI  - Privatization in the health care system of Croatia: effects on general practice
      accessibility.
AB  - This paper analyzes some effects of the privatization process in primary health
      care in Croatia, and in particular evaluates actions taken by providers to
      improve their accessibility for patients. The sample was stratified by regional
      density of practices and the status of practices in relation to privatization.
      Three groups of general practices were included in the study and were assessed
      twice (in 1997/1998 and 1999/2000): (1) 106 privatized before the beginning of
      the study; (2) 96 privatized during the study period and (3) 65 that were not yet
      privatized. The research was performed by structured interview with general
      practitioners as informants. The indicators analyzed were: possibilities of
      obtaining first and follow-up visit appointments, honouring scheduled
      appointments, scheduling visits by telephone, visiting the practitioner after
      hours and obtaining telephone advice after working hours. Number of registered
      patients in the practice and perception of patients' waiting times were also
      assessed. Privatized practices performed better in improving the accessibility of
      their services for patients: they increasingly offered the possibility for first
      and follow-up appointments at precise times, scheduled visits by telephone and
      provided telephone advice outside working hours. They showed greater intention to
      honour made appointments in order to lower their patients' waiting times. The
      study indicates that, in the initial stage of privatization, practitioners tend
      to extend accessibility by structural improvements that are not time consuming.
      It seems that providers adjust the level of offered accessibility benefits
      according to the intensity of market competitiveness. Further research is needed
      to precisely delineate the range of structural adjustments that could be expected
      by privatization and to verify the effect of observed changes on the quality of
      care and health outcomes.

PMID- 14654520
TI  - Antitumor activity of bisphosphonates.

PMID- 14654521
TI  - Targeting HER2 in brain metastases from breast cancer.

PMID- 14654522
TI  - The Role of p63 and p73 in tumor formation and progression: coming of age toward
      clinical usefulness. Commentary re: F. Koga et al., Impaired p63 expression
      associates with poor prognosis and uroplakin III expression in invasive
      urothelial carcinoma of the bladder. Clin. Cancer Res., 9: 5501-5507, 2003, and
      P. Puig et al., p73 Expression in human normal and tumor tissues: loss of
      p73alpha expression is associated with tumor progression in bladder Cancer. Clin.
      Cancer Res., 9: 5642-5651, 2003.

PMID- 14654523
TI  - Biology of childhood osteogenic sarcoma and potential targets for therapeutic
      development: meeting summary.
AB  - Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in
      adolescents. The North American pediatric cooperative groups have performed a
      series of clinical treatment trials in this disease over the past several
      decades, and biology studies of tumor tissue have been an important study
      component. A meeting was held in Bethesda, Maryland on November 29-30, 2001,
      sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and
      the National Cancer Institute-Cancer Therapy Evaluation Program with the general
      objectives: (a) to review the current state of knowledge regarding OS biology;
      (b) to identify, prioritize, and support the development of biology studies of
      potential clinical relevance in OS; and (c) to discuss the available tissue
      resources and the appropriate methods for analysis of OS samples for the conduct
      of biology studies. This report summarizes the information presented and
      discussed by the meeting participants.

PMID- 14654524
TI  - Potentiation of therapeutic immune responses against malignancies with monoclonal
      antibodies.
AB  - Immunotherapeutic monoclonal antibodies (mAbs) can be defined as those that exert
      their functions by tampering with immune system cell molecules, causing an
      enhancement of antitumor immune responses. Some of these antibodies are agonistic
      ligands for surface receptors involved in the activation of lymphocytes and/or
      antigen-presenting cells, whereas others are antagonists of mechanisms that
      normally limit the intensity of immune reactions. Several mAbs of this category
      have been described to display in vivo antitumor activity in mouse models. Only
      anti-CTLA-4 (CD152) mAb has entered clinical trials, but the preclinical effects
      described for anti-CD40, anti-CD137 (4-1BB), anti-CD102 (intercellular adhesion
      molecule-2), and regulatory T cell-depleting mAbs should lead to their prompt
      clinical development. Their use in combination with immunizations against tumor
      antigens has been reported to be endowed with synergistic properties. This new
      group of antitumor agents holds promise for at least additive effects with
      conventional therapies of cancer and deserves intensive translational research.

PMID- 14654525
TI  - An innovative phase I clinical study demonstrates inhibition of FLT3
      phosphorylation by SU11248 in acute myeloid leukemia patients.
AB  - PURPOSE: Obtaining direct and rapid proof of molecular activity in early clinical
      trials is critical for optimal clinical development of novel targeted therapies.
      SU11248 is an oral multitargeted kinase inhibitor with selectivity for fms
      related tyrosine kinase 3/Flk2 (FLT3), platelet-derived growth factor receptor
      alpha/beta, vascular endothelial growth factor receptor 1/2, and KIT receptor
      tyrosine kinases. FLT3 is a promising candidate for targeted therapy in acute
      myeloid leukemia (AML), because activating mutations occur in up to 30% of
      patients. We conducted an innovative single-dose clinical study with a primary
      objective to demonstrate inhibition of FLT3 phosphorylation by SU11248 in AML.
      EXPERIMENTAL DESIGN: Twenty-nine AML patients each received a single dose of
      SU11248, escalated from 50 to 350 mg, in increments of 50 mg and cohorts of three
      to six patients. FLT3 phosphorylation and plasma pharmacokinetics were evaluated
      at seven time points over 48 h after SU11248 administration, and FLT3 genotype
      was determined. Study drug-related adverse events occurred in 31% of patients,
      mainly grade 1 or 2 diarrhea and nausea, at higher dose levels. RESULTS:
      Inhibition of FLT3 phosphorylation was apparent in 50% of FLT3-wild-type (WT)
      patients and in 100% of FLT3-mutant patients. FLT3 internal tandem duplication
      (ITD) mutants showed increased sensitivity relative to FLT3-WT, consistent with
      preclinical predictions. The primary end point, strong inhibition of FLT3
      phosphorylation in >50% patients, was reached in 200 mg and higher dose cohorts.
      Downstream signaling pathways were also inhibited; signal transducer and
      activator of transcription 5 (STAT5) was reduced primarily in internal tandem
      duplication patients and at late time points in FLT3-WT patients, whereas
      extracellular signal-regulated kinase (ERK) activity was reduced in the majority
      of patients, independent of FLT3 inhibition. CONCLUSIONS: This novel
      translational study bridges preclinical models to the patient setting and
      provides the first evidence of anti-FLT3 activity in patients. Proof of target
      inhibition accomplishes a crucial milestone in the development of novel oncology
      therapeutics.

PMID- 14654526
TI  - Gene expression profiling in clinically localized prostate cancer: a four-gene
      expression model predicts clinical behavior.
AB  - PURPOSE: New diagnostic and prognostic molecular markers are required for
      prostate cancer, one of the most common male malignancies in Western countries.
      Gene expression profiling may help to identify genes involved in prostate
      carcinogenesis, yield clinical biomarkers, and improve tumor classification.
      EXPERIMENTAL DESIGN: To identify fundamental differences between normal and
      neoplastic prostate tissue, we used real-time quantitative RT-PCR assays to
      quantify the mRNA expression of 291 selected genes in samples of normal prostate
      and of well-documented primary, clinically localized prostate tumors. RESULTS:
      Forty-six genes showed significantly different expression in tumors relative to
      normal prostate. The dysregulated genes belong notably to the extracellular
      membrane and extracellular membrane remodeling categories and are involved in
      angiogenesis. Furthermore, we obtained a four-gene (XLKD1/LYVE1, CGA, F2R/PAR1,
      and BCL-G) model that discriminated between the seven patients with and the seven
      patients without relapse, independently of stage and grade. CONCLUSIONS: Some
      dysregulated genes are good candidates for use as molecular markers and/or
      therapeutic targets. Furthermore, differential gene expression profiling of
      clinically localized prostate tumors from relapsing and nonrelapsing patients
      identified a set of four genes with a pattern of expression that defines a
      molecular signature that could predict the clinical behavior of this disease.

PMID- 14654527
TI  - Expression genomics of cervical cancer: molecular classification and prediction
      of radiotherapy response by DNA microarray.
AB  - PURPOSE: The incidence and mortality rates of cervical cancer are declining in
      the United States; however, worldwide, cervical cancer is still one of the
      leading causes of death in women, second only to breast cancer. This disparity is
      at least partially explained by the absence of or comparatively ineffective
      screening programs in the developing world. Recent advances in expression
      genomics have enabled the use of DNA microarray to profile gene expression of
      various cancers. These expression profiles may be suitable for molecular
      classification and prediction of disease outcome and treatment response. We
      envision that expression genomics applied in cervical cancer may provide a more
      rational approach to the classification and treatment of the disease.
      EXPERIMENTAL DESIGN: In this report, we examined the expression profiles of
      cervical cancer compared with normal cervical tissues in DNA microarrays that
      contained approximately 11,000 features that correspond to either human
      transcripts with known function or anonymous expressed sequence tags. RESULTS:
      Our results showed that normal cervical tissues were completely segregated from
      the cancer samples using about 40 genes whose expressions were significantly
      different between these specimens. In addition, clinical stage IB and stage IIB
      tumors could also be classified based on their signature expression patterns.
      Most importantly, some of the tumor samples were further stratified into two
      major groups based on their response to radiotherapy, and we were able to predict
      the response of these patients to radiotherapy from their expression profiles.
      CONCLUSIONS: Gene expression profiling by DNA microarray may be used for further
      molecular classification of disease stages and prediction of treatment response
      in cervical cancer.

PMID- 14654528
TI  - Comparison of proteome between hepatitis B virus- and hepatitis C virus
      associated hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant
      cancers closely associated with chronic infection by the hepatitis B virus (HBV)
      or the hepatitis C virus (HCV) throughout the world. Differential expression of
      the proteome in HBV- and HCV-associated HCC was investigated to identify any
      useful biomarkers indicating virus-specific hepatocarcinogenesis. EXPERIMENTAL
      DESIGN: Twenty-one pairs of specimens (tumorous and surrounding nontumorous liver
      tissues) were obtained from 21 HCC patients. They were divided into three HCC
      types by viral markers: 7 hepatitis B surface antigen-positive (B-type HCC), 7
      anti-HCV-positive (C-type HCC), and 7 hepatitis B surface antigen-negative and
      anti-HCV-negative. Total proteins were analyzed by two-dimensional gel
      electrophoresis and matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry, and alterations in the proteome were examined. RESULTS: Sixty
      proteins were identified that show significant changes in the expression level
      between nontumorous and tumorous tissues. Among these, 14 proteins were commonly
      changed in all three of the HCC types, but 46 proteins showed a tendency of viral
      marker specificity. CONCLUSIONS: The identified proteins were classified
      according to the viral factor as being involved in B-type and C-type HCC. These
      results suggest strongly that the expression pattern of proteome in HCC tissues
      is closely associated with etiologic factors. The different protein profiles
      between B-type and C-type HCC indicate that the pathogenetic mechanisms of
      hepatocarcinogenesis may be different according to the viral factor, HBV and HCV.

PMID- 14654529
TI  - Impaired p63 expression associates with poor prognosis and uroplakin III
      expression in invasive urothelial carcinoma of the bladder.
AB  - PURPOSE: p63 is proposed to play roles in normal development and differentiation
      of stratified epithelia including urothelium. We recently reported that impaired
      p63 expression is a common feature of high-grade invasive urothelial carcinomas
      and associates with reduced beta-catenin. On the basis of these facts, we
      proposed that impaired p63 expression contributes to biological aggressiveness of
      urothelial neoplasms. Uroplakin (UP) III expression was also evaluated to
      investigate a possible association between loss of p63 expression and terminal
      urothelial differentiation. EXPERIMENTAL DESIGN: Expression of p63, beta-catenin,
      and UP III was immunohistochemically analyzed in 75 cystectomy specimens of high
      grade invasive bladder carcinoma. p63 expression was semiquantified and compared
      with pathological parameters, expression of beta-catenin and UP III, and cancer
      specific survival. RESULTS: Lower p63 expression was significantly associated
      with higher Tumor-Node-Metastasis (TNM) stage (P = 0.0004), lymph-node metastasis
      (P = 0.013), and reduced beta-catenin expression (P = 0.003). By univariate
      analysis, lower p63 expression, along with TNM stage and lymph-node status, were
      significantly associated with a poor prognosis (P = 0.0005), whereas reduced beta
      catenin was not. By multivariate analysis, the prognostic effect of p63
      expression was independent of TNM stage and lymph-node status with marginal
      statistical significance (P = 0.074). UP III expression was restricted to a
      subset of p63-negative carcinoma cells, including even anaplastic carcinoma
      cells. CONCLUSIONS: Impaired p63 expression characterizes biological
      aggressiveness of high-grade invasive urothelial carcinomas. Moreover, loss of
      p63 expression is a prerequisite for UP III expression. Our data suggest that p63
      plays critical roles in tumor progression and biochemical terminal
      differentiation of urothelial neoplasms.

PMID- 14654530
TI  - Irradiation reduces interstitial fluid transport and increases the collagen
      content in tumors.
AB  - PURPOSE: We have shown that the interstitial diffusion of large molecules is
      significantly hindered in tumors with high collagen levels. Because large
      therapeutic agents (e.g., monoclonal antibodies and viral vectors) will be
      combined with radiation or chemotherapy, it is significant to determine how
      cytotoxic therapies modify the transport and composition of the interstitial
      space in tumors. To test the hypothesis that radiation alters tumor interstitial
      transport, we measured tumor hydraulic conductivity (K) and hyaluronan and
      collagen type I levels after irradiation. EXPERIMENTAL DESIGN: K and the
      quantification of interstitial matrix components were determined in sections of
      s.c. implants of the human colon adenocarcinoma LS174T. K was measured on days 1
      and 5 after 10 Gy of irradiation or on day 5 after 30 Gy of irradiation. RESULTS:
      Compared with control tumors, K decreased by approximately 12-fold after 10 or 30
      Gy of irradiation on day 5. At 24 h after irradiation with 10 Gy, the decrease in
      K was not significant. Five days after 10 and 30 Gy of irradiation, the decrease
      in K was associated with significantly higher levels of collagen type I. The
      collagen type I content was not changed 24 h after irradiation with 10 Gy.
      Irradiation did not significantly increase hyaluronan levels in LS174T tumors.
      CONCLUSIONS: After irradiation, the decrease in K and increase in collagen type I
      levels could significantly hinder the convective movement and diffusion of large
      therapeutic agents in tumors.

PMID- 14654531
TI  - Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of
      intracerebral metastatic breast cancer.
AB  - PURPOSE: The monoclonal antibody (MAb) trastuzumab (Herceptin) effectively treats
      HER2-overexpressing extracerebral breast neoplasms. Delivery of such
      macromolecule therapeutic agents to intracerebral metastases, however, is limited
      by the tight junctions characteristic of the cerebral vasculature. Direct
      intracerebral microinfusion (ICM) is a technique that bypasses this blood-brain
      barrier and allows for a greater delivery of drugs directly into intracerebral
      tumors. EXPERIMENTAL DESIGN: A human breast cancer cell line transfected to
      overexpress HER2, MCF-7/HER2-18, was transplanted into the cerebrum of athymic
      rats. Saline, trastuzumab, or an isotype-matched control MAb was delivered
      systemically or by ICM to assess toxicity and efficacy. RESULTS: No clinical or
      histological toxicity related to trastuzumab was evident under any of the
      conditions studied. Delivery of trastuzumab (2 mg/kg) i.p. led to a median
      survival of 26.5 days, whereas treatment with trastuzumab (2 mg/kg) by ICM
      increased the median survival by 96% to 52 days, with two of nine rats surviving
      >120 days (P = 0.009). Treatment with an isotype-matched control MAb (16 mg/kg)
      resulted in a median survival of 21 days, which did not differ significantly from
      the survival of rats treated by ICM with saline (16 days; P = 0.42). Treatment by
      ICM with trastuzumab (16 mg/kg) led to a median survival of 45 days, with 2 of 10
      rats surviving >120 days. These results represent 181% and 114% increases in
      median survival over the saline and MAb controls, respectively (P < 0.001).
      CONCLUSION: ICM of trastuzumab is safe and superior to systemic delivery as
      therapy for HER2-overexpressing intracerebral neoplasms in an athymic rat model.

PMID- 14654532
TI  - In vitro affinity maturation of a specificity-determining region-grafted
      humanized anticarcinoma antibody: isolation and characterization of minimally
      immunogenic high-affinity variants.
AB  - PURPOSE: HuCC49V10 (V10), a humanized anticarcinoma monoclonal antibody (Ab)
      CC49, was generated by grafting only the specificity-determining regions (SDRs)
      of CC49 onto the variable light and variable heavy frameworks of the human Abs
      LEN and 21/28'CL, respectively. SDRs are those residues of the complementarity
      determining regions that are most critical for antigen (Ag) binding. Compared
      with HuCC49, which was developed by conventional complementarity-determining
      region grafting, V10 has lower reactivity to the sera from patients who were
      previously given murine CC49 in clinical trials, although its Ag-binding affinity
      is 2-3-fold lower than that of HuCC49. To generate variants of V10 with higher Ag
      binding affinity and lower sera reactivity, in vitro affinity maturation of V10
      was carried out using phage display technique. EXPERIMENTAL DESIGN: A limited
      library of Fabs was generated by replacing some of the SDRs with all possible
      residues located at the corresponding positions in human Abs. The library was
      enriched, by several rounds of panning, in Fabs that have high affinity for the
      TAG-72 Ag. The clones encoding the best binders were expressed in insect cells as
      whole Abs that were purified and characterized. RESULTS: Competition
      radioimmunoassay and surface plasmon resonance measurements showed that two of
      the isolates, V14 and V15, have higher binding affinity than that of V10. In
      addition, the surface plasmon resonance analysis showed that the variants V14 and
      V15, compared with the parental V10, have lower reactivity to the anti-V region
      Abs using sera from patients who received murine CC49. CONCLUSIONS: The two
      isolates, V14 and V15, which show higher Ag-binding reactivity and lower sera
      reactivity than the parental V10 Ab, are potentially more useful clinical
      reagents. These results demonstrate that phage display can be used to isolate
      variants of an Ab that are potentially less immunogenic in patients than the
      parental Ab from which they are derived.

PMID- 14654533
TI  - Development of an orthotopic model to study the biology and therapy of primary
      human lung cancer in nude mice.
AB  - PURPOSE: This study was conducted to develop biologically relevant animal models
      of human lung cancer that are reproducible, inexpensive, and easy to perform.
      EXPERIMENTAL DESIGN: Human lung adenocarcinoma (PC14PE6), bronchioloalveolar
      carcinoma (NCI-H358), squamous cell carcinoma (NCI-H226), poorly differentiated
      non-small cell lung cancer (NCI-H1299 and A549), or small cell lung cancer (NCI
      H69) cells in Matrigel were injected percutaneously into the left lungs of nude
      mice. The growth pattern of the different lung cancer tumors was studied. For
      PC14PE6 and NCI-H358, the growth pattern in the subcutis and the response to
      paclitaxel were also studied. RESULTS: As is observed for human primary lung
      cancer, tumors formed from a single focus of disease and progressed to a
      widespread and fatal thoracic process characterized by diffuse dissemination of
      lung cancer in both lungs and metastasis to intra- and extrathoracic lymph nodes.
      When the lung cancer cell lines were implanted s.c., systemic therapy with
      paclitaxel induced tumor regression. However, only a limited therapeutic response
      to paclitaxel was observed when the same cells were implanted orthotopically into
      the lung. Immunohistochemical analysis of tumor tissue revealed increased
      expression of the proangiogenic factors interleukin 8, basic fibroblast growth
      factor, and vascular endothelial growth factor/vascular permeability factor.
      CONCLUSIONS: Our orthotopic models of human lung cancer confirm the "seed and
      soil" concept and likely provide more clinically relevant systems for the study
      of both non-small cell lung cancer and small cell lung cancer biology, and for
      characterizing novel therapeutic strategies.

PMID- 14654534
TI  - A phase I and pharmacokinetic study of ILX-295501, an oral diarylsulfonylurea, on
      a weekly for 3 weeks every 4-week schedule in patients with advanced solid
      malignancies.
AB  - PURPOSE: This study was conducted to assess the feasibility of administering the
      oral diarylsulfonylurea (DSU) ILX-295501 on a weekly for 3 weeks every 4-week
      schedule. The study also sought to determine the maximum tolerated dose (MTD) of
      ILX-295501 on this schedule, characterize its pharmacokinetic behavior, and seek
      preliminary evidence of anticancer activity. EXPERIMENTAL DESIGN: The initial
      starting dose of ILX-295501 was 100 mg/m(2), which was equivalent to one-sixth of
      the highest dose that did not induce irreversible toxicity in dogs, and, using a
      modified Fibonnaci search scheme to guide dose level selection, the following
      dose levels were evaluated: 100, 200, 400, 600, 900, 1350, and 1800 mg/m(2).
      Because severe toxicities were being reported in other trials at doses that
      encompassed this range and a cumulative toxicity profile was emerging, the study
      was suspended and then reinitiated to further reevaluate the lower dosing range.
      In the second part of the study, the following dose levels were selected a priori
      for evaluation: 400, 800, 1000, 1250, and 1500 mg/m(2); and a modified continual
      reassessment model was used for dose assignment to determine the MTD, which was
      defined a priori as the highest dose in which the incidence of dose-limiting
      toxicity in the first course did not exceed 20%. RESULTS: Forty-nine patients
      were treated with 142 courses of ILX-295501 at doses ranging from 100 to 1800
      mg/m(2). The incidences of dose-limiting toxicity, principally neutropenia and
      thrombocytopenia, were unacceptably high at ILX-295501 doses exceeding 1000
      mg/m(2), which was determined to be the MTD for both minimally pretreated and
      heavily pretreated (HP) patients. In contrast to the first generation of DSUs,
      particularly sulofenur, clinically relevant levels of oxidized hemoglobin
      (methemoglobin) and secondary hemolytic anemia, were not noted. One HP patient
      with non-small cell lung carcinoma experienced a partial response.
      Pharmacokinetic studies revealed that ILX-295501 was absorbed slowly, with peak
      plasma concentrations (C(max)) achieving 6.02 h, on average, after oral
      administration. The pharmacokinetic behavior of ILX-295501 was characterized by
      dose proportionality, a relatively small apparent volume of distribution at
      steady state (V(ss)/F), averaging 8.02 +/- 14.08 liters, and low apparent total
      body clearance (CL(t)/F) rate (mean, 0.036 +/- 0.116 liters/h). The initial drug
      distribution phase was rapid [harmonic mean half-life (t(1/2alpha)), 2.1 +/- 7.0
      min], whereas the terminal elimination phase was slow (harmonic mean t(1/2beta,)
      150.6 +/- 80.2 h). CONCLUSIONS: The recommended dose for Phase II studies of the
      oral DSU ILX-295501 administered weekly for 3 weeks every 4 weeks is 1000
      mg/m(2)/day for both minimally pretreated and HP patients. The characteristics of
      the myelosuppressive effects of ILX-295501, the paucity of severe
      nonhematological toxicities, and preliminary antitumor activity warrant disease
      directed evaluations of ILX-295501.

PMID- 14654535
TI  - The immunomodulating effect of interferon-gamma intravesical instillations in
      preventing bladder cancer recurrence.
AB  - PURPOSE: The purpose is to investigate the prophylactic effect of intravesically
      instillated recombinant IFN-gamma against recurrence of superficial transitional
      cell carcinoma of the bladder and to evaluate its effect in local immune
      response, presumably mediating its therapeutic efficacy. EXPERIMENTAL DESIGN: We
      prospectively randomized in two groups 123 patients with initially diagnosed
      superficial transitional cell carcinoma and stage Ta, T1, grade 2 tumors, who
      underwent transurethral tumor resection (TUR). In group A, 60 patients received
      IFN-gamma (1.5 x 10(7) IU/instillation), whereas 63 patients, consisting of the
      control group B, received mitomycin C (40 mg/instillation). The annual
      administration schedule consisted of eight weekly followed by four biweekly and
      then by eight monthly instillations for both regimens. We also analyzed the
      immunophenotype of the intratumoral and intramural leukocytes by
      immunohistochemical and flow-cytometric techniques. To this purpose, tumor
      samples were obtained at TUR and random biopsies at TUR and during cystoscopy at
      6 and 12 months, and bladder washings were collected before TUR and at
      preselected time points. RESULTS: In group A, 44 of 60 (73.4%) patients, and in
      group B, 36 of 63 (57.2%) patients, were tumor free during the median follow-up
      period of 26.5 months (range, 3-49 months). IFN-gamma was well tolerated. Six
      months after starting treatment, follicular cystitis was detected in patients
      responding to IFN-gamma. After IFN-gamma instillations, statistically significant
      increases in T cells, T-helper cells, T-cytotoxic cells, natural killer cells,
      and total leukocytes, as well as in the number of B cells expressing
      intercellular adhesion molecule-1 and total leukocytes expressing HLA-DR, were
      observed by flow cytometry in tissue specimens and bladder washings. CONCLUSIONS:
      Recombinant IFN-gamma appears to be effective against stage Ta, T1, grade 2
      bladder tumors' recurrence. Recruitment and activation of intramural leukocytes
      seem to be involved in the mechanism of IFN-gamma action.

PMID- 14654536
TI  - Immunization of cancer patients with HER-2/neu-derived peptides demonstrating
      high-affinity binding to multiple class II alleles.
AB  - PURPOSE: The purpose of this study was to immunize patients with HER-2/neu
      overexpressing cancer with a multipeptide vaccine comprised of four class II HER
      2/neu peptides that had been identified as the most immunogenic in a previous
      clinical trial. Furthermore, we questioned whether MHC binding affinity could
      predict the in vivo immunogenicity of the HER-2/neu helper peptides. EXPERIMENTAL
      DESIGN: Four putative class II HER-2/neu peptides, which were found to generate
      detectable specific T-cell responses (stimulation index > 2) in a majority of
      patients in a previous study, were used to formulate a single vaccine. The
      multipeptide vaccine was administered intradermally with granulocyte macrophage
      colony-stimulating factor as an adjuvant. Ten patients with HER-2/neu
      overexpressing breast or lung cancer were enrolled. HER-2/neu peptide-and protein
      specific T cell and antibody immune responses were measured. Competitive
      inhibition assays were used to analyze the class II HER-2/neu peptides for their
      binding affinity to 14 common HLA-DR alleles. RESULTS: Twenty-five percent of
      patients developed HER-2/neu peptide-specific T-cell immunity, and 50% developed
      HER-2/neu peptide-specific antibody immunity. No patient developed HER-2/neu
      protein-specific T cell or antibody immunity. The majority of peptides exhibited
      high binding affinity, in vitro, to >/==" BORDER="0">3 of the 14 DR alleles
      analyzed. CONCLUSION: The group of peptides used in this study demonstrated high
      binding affinity to multiple DR alleles suggesting that in vitro binding affinity
      may be able to predict the in vivo immunogenicity of class II peptides. However,
      only a minority of patients immunized with the multipeptide vaccine developed HER
      2/neu peptide-specific T cell or antibody immunity, and none developed HER-2/neu
      protein-specific immunity.

PMID- 14654537
TI  - Recombinant human erythropoietin therapy is very effective after an autologous
      peripheral blood stem cell transplant when started soon after engraftment.
AB  - PURPOSE: Previous trials of recombinant human erythropoietin (rHuEpo) therapy
      after autologous hematopoietic stem cell transplantation have administered very
      high doses of i.v. rHuEpo starting on day 1 and continuing for 1-2 months until
      erythroid engraftment and have shown no benefit of rHuEpo therapy. We sought to
      establish a more effective use of rHuEpo in this setting. EXPERIMENTAL DESIGN: In
      this report, we show in a first cohort of 45 lymphoma or myeloma patients
      undergoing peripheral blood stem cell transplant (control group) that endogenous
      erythropoietin levels are high for the degree of anemia during the first 3 weeks
      after transplant but become adequate or slightly decreased thereafter. We thus
      enrolled 41 consecutive similar patients in a trial of rHuEpo therapy at a dose
      of 500 units/kg/week started on day 30 after the transplant. RESULTS: The 12-week
      probability of achieving hemoglobin (Hb) levels of 13 g/dl was 87% in rHuEpo
      treated patients versus 14% in controls (P = 0.0001). Mean Hb levels were
      significantly higher in the rHuEpo group than in the control group from day 42
      through day 150 after transplant (Ps of <0.05 to <0.001). Two of 41 patients in
      the rHuEpo group versus 12 of 45 patients in the control group had Hb levels of
      <9 g/dl between day 42 and day 100 after the transplant (P = 0.0078).
      CONCLUSIONS: Anemia after autologous peripheral blood stem cell transplant is
      exquisitely sensitive to rHuEpo when therapy is started soon after engraftment.
      This is the first convincing report showing that rHuEpo is effective in this
      setting. Our data set the stage for a more rational use of rHuEpo after
      autologous hematopoietic stem cell transplantation and should renew interest in
      erythropoietin therapy in this setting. Prospective, randomized trials should
      investigate the impact of rHuEpo therapy on transfusion requirements and quality
      of life.

PMID- 14654538
TI  - Tissue inhibitor of metalloproteinase-2 as a multifunctional molecule of which
      the expression is associated with adverse prognosis of patients with urothelial
      bladder carcinomas.
AB  - PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix
      metalloproteinase (MMP) activity controlling the breakdown of extracellular
      matrix components and, thus, play an important role in the process of invasion
      and metastasis. Moreover, there are several new functions, growth control,
      apoptosis, and angiogenesis-, in which TIMPs seem to be involved. The aim of this
      study was to elucidate the role of TIMP-2 in human urothelial cancer assessing
      TIMP-2 protein expression in 106 urothelial bladder carcinomas and evaluating its
      importance relative to clinicopathologic parameters (age, gender, histological
      grade, and stage) and patient survival, as well as to markers associated with
      cell growth and apoptosis (Ki-67, p53, and bcl-2). EXPERIMENTAL DESIGN:
      Immunohistochemistry (avidin-biotin complex method-horseradish peroxidase) was
      performed to detect TIMP-2, Ki-67, p53, and bcl-2 proteins using monoclonal and
      polyclonal antibodies. Statistical analysis was univariate and multivariate.
      RESULTS: TIMP-2 immunohistochemical expression was observed in stromal
      fibroblasts and in cancerous cells in 26.4% and 69.8% of cases, respectively.
      TIMP-2 stromal but not cancerous cell expression associated significantly with
      the high histological grade of carcinomas (P < 0.0001) and the advanced stage of
      the disease (P = 0.001). TIMP-2 either stromal or cancerous cell expression
      correlated significantly with the expression of Ki-67 proliferation indice (P =
      0.02 and P = 0.044, respectively) and the mutant p53 protein (P = 0.043 and P =
      0.045, respectively). In univariate survival analysis patients with positive TIMP
      2 stromal cell immunohistochemical expression had a significantly worse overall
      survival in comparison with TIMP-2 stromal cell-negative patients (log rank test:
      P = 0.0002). However, in multivariate survival analysis the only independent
      survival factors were the stage of the disease and patient age. CONCLUSIONS: TIMP
      2 protein expression in either the stromal or cancerous cells is associated with
      the proliferation index Ki-67 and the apoptosis-related protein p53. These
      findings are in keeping with in vitro studies reporting a growth-promoting
      ability of TIMP-2 and its involvement in apoptosis regulation. On the other hand,
      TIMP-2 stromal cell expression only was associated with adverse prognosis of
      urothelial bladder cancer patients.

PMID- 14654539
TI  - TP53 gene mutations predict the response to neoadjuvant treatment with 5
      fluorouracil and mitomycin in locally advanced breast cancer.
AB  - PURPOSE: Recent studies have found an association between certain TP53 mutations
      and resistance to anthracycline-based primary medical therapy in breast cancer.
      The purpose of this study was to investigate whether TP53 mutational status also
      might influence the response to a non-anthracycline-containing regimen in primary
      breast cancer. EXPERIMENTAL DESIGN: Thirty-five patients with locally advanced
      breast cancer were investigated for TP53 mutations before receiving combination
      chemotherapy with 5-fluorouracil (1000 mg/m(2) on days 1 and 2) and mitomycin (6
      mg/m(2) on day 2), administered every 3 weeks for 2-10 cycles in the neoadjuvant
      setting. RESULTS: Mutations in the TP53 gene, in particular those affecting loop
      domains L2 or L3 of the p53 protein, were associated with lack of response to
      chemotherapy (i.e., increase in the diameter product of tumor lesion by >/=25%; P
      = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains,
      respectively). No statistically significant correlation between TP53 LOH and
      response to therapy was seen. CONCLUSION: This study revealed a significant
      association between lack of response to 5-fluorouracil and mitomycin and
      mutations affecting the L2/L3 domains of the p53 protein. Together with our
      previous finding that such mutations predict resistance to weekly doxorubicin,
      our data suggest that mutations affecting this particular domain of the p53
      protein may cause resistance to several different cytotoxic compounds applied in
      breast cancer treatment.

PMID- 14654540
TI  - A large-scale gene expression comparison of microdissected, small-sized
      endometrial cancers with or without hyperplasia matched to same-patient normal
      tissue.
AB  - PURPOSE: Type I endometrial cancer is accompanied by hyperplasia and type II
      endometrial cancer is not. The purpose of our study is to identify genes involved
      in carcinogenesis of endometrial cancer, especially those differentially
      expressed by type I and type II cancers. EXPERIMENTAL DESIGN: Using a cDNA array
      technique, we examined expression of 1176 cancer-related genes in endometrial
      cancer cells sampled from 21 tumors with a diameter of <10 mm, and we compared
      the expression patterns of the tumor cells with expression patterns of
      corresponding normal endometrial cells. Of these, 10 cases were type I cancers,
      and 11 cases were type II cancers. Laser capture microdissection directed precise
      separation of cells of interest from stromal cells. In cancer cells relative to
      normal cells, we identified genes that were commonly up- and down-regulated. Then
      we identified genes differentially expressed by the two types of cancer. Finally,
      in situ protein expression of some of these gene products was examined using
      immunohistochemistry. RESULTS: Of 1176 genes examined, 32 genes were up
      regulated, and 58 were down-regulated in cancer cells (P < 0.05). Between the two
      types of cancer, 45 genes were highly expressed in type I cancers, and 24 were
      highly expressed in type II. Immunohistochemistry confirmed that P-cadherin
      expression was cancer specific, and vascular endothelial growth factor-C and MLH1
      expression were limited to type I and type II cancers, respectively. CONCLUSIONS:
      A more accurate way of assessing gene expression during endometrial
      carcinogenesis shows evidence of providing candidate genes for use in conquering
      endometrial carcinoma.

PMID- 14654541
TI  - CpG island methylation in sporadic and neurofibromatis type 2-associated
      schwannomas.
AB  - PURPOSE: The purpose of this research was to examine the DNA methylation profile
      of schwannomas. EXPERIMENTAL DESIGN: We examined the DNA methylation status of 12
      tumor-related genes (NF2, RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK,
      THBS1, caspase-8, TP53, and GSTP1) in 44 sporadic and/or NF2-associated
      schwannomas using methylation-specific PCR. RESULTS: The most frequently
      methylated genes were THBS1 (36%), p73 (27%), MGMT (20%), NF2 (18%), and TIMP-3
      (18%). The RB1/p16INK4a gene pair displayed aberrant methylayed alleles in 15% of
      cases, whereas methylation was relatively rare in the other genes (<5%).
      Methylation was tumor specific because it was absent in two nonneoplastic nerve
      sheath samples and two nonneoplastic brain samples studied as controls.
      CONCLUSIONS: Our findings indicate that aberrant methylation seems to be a
      mechanism for NF2 gene inactivation, considered an early step in schwannoma
      tumorigenesis, and as well, aberrant hypermethylation of other tumor-related
      genes might represent secondary events that also contribute to the development of
      these tumors.

PMID- 14654542
TI  - PRL-3 expression in metastatic cancers.
AB  - PURPOSE: Expression of the PRL-3 tyrosine phosphatase is elevated in liver
      metastases derived from colorectal cancer (CRC). We sought to determine the
      cellular basis of this elevation and assess the expression of PRL-3 in metastatic
      lesions derived from cancers of the colon and other tissues. EXPERIMENTAL DESIGN:
      We developed modifications of in situ hybridization methods that facilitated the
      study of paraffin-embedded sections. We also evaluated PRL-3 gene copy numbers
      using fluorescence in situ hybridization and developed antibodies to assess PRL-3
      subcellular localization. RESULTS: PRL-3 mRNA expression was elevated in nearly
      all metastatic lesions derived from CRCs, regardless of the site of metastasis
      (liver, lung, brain, or ovary). Expression was found in neoplastic cells,
      although tumor endothelium also expressed the gene. In contrast, little or no PRL
      3 expression was observed in normal colon, nonmetastatic primary cancers, or
      metastatic lesions derived from cancers other than those of the colon (pancreas,
      stomach, or esophagus). Interphase fluorescence in situ hybridization confirmed
      that gene amplification was not the major cause of PRL-3 overexpression.
      Immunohistochemical analysis with anti-PRL-3 antibodies showed a cell membrane
      localization, consistent with the predicted isoprenylation of the protein.
      CONCLUSIONS: These studies establish an unexpected and unprecedented specificity
      in metastatic gene expression profiles: PRL-3 is apparently expressed in CRC
      metastases to any organ but is not expressed in metastases of other cancers to
      the same organs or in nonmetastatic CRCs. PRL-3 is also expressed in tumor
      vasculature, regardless of the tumor source. These data raise intriguing
      questions about the role of protein phosphorylation in angiogenesis and cell-type
      specific metastatic processes.

PMID- 14654543
TI  - Use of 11p15 mucins as prognostic factors in small adenocarcinoma of the lung.
AB  - PURPOSE: Patients with small adenocarcinoma of the lung (SACL) generally have a
      good prognosis. However, some SACL cases show lymph node metastasis, with poor
      prognosis. The expression pattern of 11p15 mucins (clustered on the p15 arm of
      the chromosome 11) is known to change during carcinogenesis in lung cancer.
      EXPERIMENTAL DESIGN: We evaluated the expression of the 11p15 mucins (MUC2,
      MUC5AC, and MUC6) in 79 surgical specimens of SACL cases by immunohistochemical
      analysis. Lymph node metastasis was estimated by pathological staging. RESULTS:
      Six (7.6%) and 11 (13.9%) of the 79 SACL cases showed MUC2 and MUC6 expression,
      respectively. Three SACL cases showed both MUC2 and MUC6 expression, and a
      significant correlation was found between MUC2 and MUC6 expression (Fisher's
      test, P = 0.033). Six (7.6%) SACL cases showed MUC5AC expression. Five of the 6
      cases with MUC2 expression and 6 of the 11 cases with MUC6 expression were had
      lymph node metastasis. SACL cases with MUC2 or MUC6 expression showed a
      significantly higher incidence of nodal metastasis than those without expression
      (P < 0.001 and P = 0.006, chi(2) test, respectively). There was no significant
      correlation between MUC5AC expression and nodal involvement in SACL, whereas
      three of the six cases with MUC5AC expression showed lymph node metastasis. The
      SACL cases with MUC2 expression had a significantly poorer prognosis than those
      without MUC2 expression (P = 0.011, log-rank test). CONCLUSIONS: These results
      suggest that 11p15 mucins MUC2 and MUC6 are related to lymph node metastasis in
      SACL.

PMID- 14654544
TI  - Clinical screening of gene rearrangements in childhood leukemia by using a
      multiplex polymerase chain reaction-microarray approach.
AB  - PURPOSE: Currently, many forms of leukemia are considered potentially curable,
      with prognosis and clinical outcome strongly dependent on the underlying
      molecular pathophysiology. A substantial number of leukemia patients harbor
      nonrandom karyotypic abnormalities that define subgroups with unique biological
      and clinical features. For detection of these types of gene rearrangements, a
      combination of multiplex RT-PCR with hybridization on oligonucleotide gel array
      was presented previously, which identified five chromosomal translocations with
      fusion variants. In the present study, additional clinically relevant
      translocations were included in our analysis using a second generation of
      microarrays. We also expanded significantly on the clinical correlation of our
      findings. EXPERIMENTAL DESIGN: An oligonucleotide microarray was designed for
      hybridization with products of a multiplex RT-PCR to identify the following
      translocations: t(9;22)p190, t(4;11), t(12;21), t(1;19), typical for acute
      lymphoblastic leukemia; t(9;22)p210 for chronic myeloid leukemia; and t(8;21),
      t(15;17), inv16, typical for acute myeloblastic leukemia. RESULTS: To demonstrate
      the potential clinical application of the method, 247 cases of childhood leukemia
      were screened, and the above-mentioned gene rearrangements were found in 30% of
      cases. The sensitivity and specificity of the assay is comparable with the RT-PCR
      technique, so that it can be used to follow minimal residual disease. The
      feasibility of an additional refinement of the method, on-chip-multiplex PCR, has
      been successfully demonstrated by identifying a common translocation, t(9;22), in
      chronic myeloid leukemia. CONCLUSIONS: Our data suggest that the microarray-based
      assay can be an effective and reliable tool in the clinical screening of leukemia
      patients for the presence of specific gene rearrangements with important
      diagnostic and prognostic implications. The method is amenable for automation and
      high-throughput analysis.

PMID- 14654545
TI  - Immunohistochemical detection of occult lymph node metastases in non-small cell
      lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial
      9761.
AB  - PURPOSE: Our purpose was to study the detection of occult metastases (OM) in
      regional lymph nodes using immunohistochemical stain for cytokeratin, and for
      this study we targeted clinical stage I patients with non-small cell lung cancer.
      EXPERIMENTAL DESIGN: The study comprised the first 193 patients entered onto
      Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1
      2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of
      their primary tumors. Samples of the primary tumor and lymph nodes were taken
      from lymph node stations 2-12 and shipped to a central laboratory, where each
      lymph node was histologically processed and stained with H&E as well as with
      immunohistochemical stain using antibodies to cytokeratin (AE1/3). RESULTS:
      Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us
      to detect 18 positive lymph nodes, immunohistochemical staining allowed us to
      detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those
      detectable only by immunohistochemistry (IHC)], and there was 1 metastasis
      detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in
      N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining
      upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9
      patients to N2, and IHC added another 11. We also uncovered new details about the
      way in which H&E detection depends on metastatic tumor burden. Specifically, for
      the probability of detecting metastases by H&E to exceed 0.50, the maximum
      diameter of the metastasis must be greater than 0.23 mm. CONCLUSIONS: IHC detects
      greater than twice as many positive regional lymph nodes as does H&E staining,
      and the foci of tumor it detects are significantly smaller than those detected by
      H&E staining.

PMID- 14654546
TI  - Alterations in the mitochondrial displacement loop in lung cancers.
AB  - PURPOSE: Alterations of the noncoding displacement (D) loop of mitochondrial DNA
      are present in many cancers. These alterations include numerical changes in a
      homopolymeric C tract (PCT) at positions 303-309 and single base substitutions
      (SBS). We determined the frequency of D-loop alterations in lung cancer cell
      lines and tumors, and related them to clinicopathologic features. EXPERIMENTAL
      DESIGN: We sequenced the entire D-loop of 28 lung cancer cell lines [12 small
      cell lung cancer (SCLC) and 16 non-small cell lung cancer (NSCLC)] and matched B
      lymphoblastoid cell lines. In 55 resected NSCLCs and corresponding nonmalignant
      lungs we determined the length of the PCT. RESULTS: In nonmalignant cell lines
      and tissues the most frequent PCT repeat number was seven (36 of 83; 43%) with a
      range of six to nine. Alterations, often multiple, were present in 17 of 28 (61%)
      of the cell lines, including 8 of 12 SCLC (67%) and 9 of 16 NSCLC (56%) lines.
      They consisted of SBS in 8 of 28 lines (29%), all of which were homoplasmic, and
      PCT changes in 14 of 28 (50%) lines, 8 of which were homoplasmic. Of interest,
      95% (40 of 42) of the SBS were present within the two hypervariable regions in
      the D-loop. Because SBS were more frequent if PCT changes were present, only the
      PCT number was determined in resected samples. PCT changes were present in 11 of
      55 (20%) of the NSCLC tumors. Changes were never noted in tumors when the PCT
      number in the nonmalignant tissue was seven, and only two tumor cell lines had
      changes when the PCT number in the matched lymphoblastoid cell line was seven.
      These changes were higher in squamous cell carcinomas (8 of 25; 32%) than in
      adenocarcinomas (3 of 30; 10%; P = 0.04) and in large tumors (T3 and T4; 7 of 20;
      35%) compared with smaller tumors (T1 and T2; 4 of 35; 11%; P = 0.04). Smoking
      history, gender, age, and stage were not related to frequency of PCT change.
      CONCLUSIONS: Our findings indicate that D-loop alterations are frequent in lung
      cancers and their cell lines, and that these changes are weakly associated with
      certain clinical parameters. In tumors PCT changes were only present when the
      corresponding nonmalignant lung demonstrated a variation from the most common
      repeat number of seven.

PMID- 14654547
TI  - p73 Expression in human normal and tumor tissues: loss of p73alpha expression is
      associated with tumor progression in bladder cancer.
AB  - PURPOSE: To characterize the expression profile of p73 in human normal tissues by
      immunohistochemistry (IHC) and to analyze the correlation between p73 expression
      and bladder cancer progression. EXPERIMENTAL DESIGN: CJDp73 was characterized for
      p73alpha detection in Western blot and IHC through its application to isoform
      transfected 293 cells. Normal tissues were analyzed by IHC with the CJDp73
      antiserum. Transitional cell carcinoma (TCC)-derived cell lines were subjected to
      reverse transcription-PCR and Western blot. TCC tissue microarrays were analyzed
      for p73alpha expression by IHC, and the results were statistically analyzed.
      RESULTS: p73 immunostaining was nuclear and restricted to epithelial cells of
      certain organs such as squamous epithelium of the epidermis and transitional
      epithelium of the bladder. The expression was also observed in certain
      specialized glandular epithelia such as acinar cells of breast and parotid gland.
      Four of seven TCC-derived cell lines had low to undetectable p73alpha protein
      levels. We found undetectable or low p73alpha expression in 104 of 154 (68%) TCC
      cases, this phenotype being more frequently observed in invasive tumors when
      compared with superficial lesions. This association was statistically significant
      (P < 0.0001). We also observed a significant association between p53, p63, and
      p73alpha alterations with bladder cancer progression (P < 0.0001). CONCLUSIONS:
      p73alpha plays a tumor suppressor role in bladder cancer, and its inactivation
      occurs through an epigenetic mechanism, most probably involving protein
      degradation.

PMID- 14654548
TI  - Jun activation domain binding protein 1 expression is associated with low
      p27(Kip1)levels in node-negative breast cancer.
AB  - PURPOSE: The purpose is to evaluate expression levels of Jun activation domain
      binding protein 1 (JAB1) in breast cancer tissue and adjacent normal tissue, to
      determine whether JAB1 expression is associated with p27(Kip1) expression in
      invasive breast carcinomas, and to evaluate the prognostic significance of JAB1
      and p27(Kip1) in node-negative breast cancer. EXPERIMENTAL DESIGN: JAB1 levels
      were measured in 10 matched pairs of invasive breast tumor tissue and adjacent
      normal tissue using Western blot analysis. We also investigated the
      immunoreactivity of JAB1 and p27(Kip1) levels in paraffin-embedded tissue
      specimens from 220 patients with node-negative breast cancer who had not received
      adjuvant systemic therapy. The median follow-up was 15 years. RESULTS: JAB1 was
      expressed at higher levels in invasive tumors than in adjacent normal tissue (P =
      0.01). JAB1 overexpression was observed in 57% of invasive breast cancers. Low
      levels of p27(Kip1) were noted in 70% of the tumor specimens. We found an inverse
      correlation between JAB1 and p27(Kip1) expression levels (P = 0.01). JAB1
      overexpression was associated with patient age of at least 50 years (P = 0.03)
      and tumor size of </=2 cm (P = 0.01). Elevated levels of p27(Kip1) were
      associated with low nuclear grade (P = 0.01). At 5 years of follow-up, neither
      JAB1 nor p27(Kip1) expression was related to disease-free survival. CONCLUSIONS:
      These data indicate that JAB1 is commonly overexpressed in invasive breast
      carcinomas. JAB1 overexpression is associated with low levels of p27(Kip1) in
      node-negative breast cancer. In this study, JAB1 and p27(Kip1) were not
      independent prognostic factors.

PMID- 14654549
TI  - Immunohistochemical and mutational analyses of beta-catenin, Ki-ras, and p53 in
      two subtypes of colorectal mucinous carcinoma.
AB  - PURPOSE: The adenoma-carcinoma sequence theory is accepted in carcinogenesis of
      colorectal carcinoma. To elucidate the nature and genetic alterations in
      colorectal mucinous carcinoma (MC), we analyzed clinical and pathological
      characteristics of colorectal MC and nonmucinous carcinoma (NMC), and,
      furthermore, we compared the prognoses and the statuses of the Wnt signaling
      pathway, Ki-ras, and p53 in these two subtypes. EXPERIMENTAL DESIGN: Samples of
      colorectal MC obtained by surgical resections from 41 patients during the period
      from 1980 to 1999 were classified into fixed (FIX) type and floating (FLO) type
      (22 and 19 cases, respectively). The statuses of the Wnt signaling pathway and
      p53 protein were estimated by immunohistochemistry of beta-catenin and p53
      proteins, respectively. The mutations in the Ki-ras gene were examined by direct
      sequencing. RESULTS: The prognosis of colorectal MC was poorer than that of NMC
      at both stage II and stage III (P = 0.0037 and <0.0001, respectively). The
      survival rate of patients with the FLO type of MC was lower than that of patients
      with the FIX type (P = 0.021). Although the results of immunohistochemistry of
      beta-catenin and mutational analysis of the Ki-ras gene in the two subtypes were
      not significantly different; the rate of positive nuclear staining of p53 was
      lower in the FLO type than in the FIX type (P = 0.04). CONCLUSIONS: Colorectal
      MC, particularly the FLO type, has a more aggressive nature than does colorectal
      NMC. The FLO type of colorectal MC may develop through different mechanisms from
      those through which NMC and the FIX type develop.

PMID- 14654550
TI  - Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine
      cervical carcinomas.
AB  - PURPOSE: Hypoxia is associated with adverse outcome for a number of solid tumors,
      including cervical carcinomas. Direct pO(2) measurement requires specialized
      equipment and expertise that is not generally available. Immunohistochemical
      measurement of intrinsic tissue markers of hypoxia is an alternative approach.
      Recent studies suggest that carbonic anhydrase IX (CA IX), which is regulated via
      hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia.
      EXPERIMENTAL DESIGN: Biopsies were obtained from 110 patients with locally
      advanced cervical carcinoma treated with radiotherapy or chemoradiotherapy.
      Tissue sections were labeled using an immunofluorescence technique and CA IX
      expression in the viable tumor area measured using a semiautomated fluorescence
      image analysis technique. Results were compared with direct pO(2) values obtained
      using an Eppendorf probe and to patient outcome. Intratumoral heterogeneity of CA
      IX expression was examined in a subgroup of patient who underwent multiple
      biopsies. RESULTS: The median percentage of tumor area staining for CA IX was
      3.56 (range, 0.01-58.85). CA IX staining did not correlate with the Eppendorf
      pO(2) measurements. Whereas the latter values were predictive of patient outcome,
      the CA IX levels were not. Measurement of CA IX in multiple biopsies indicated
      that intratumoral heterogeneity accounted for 41% of the total variance in the
      data set. CONCLUSIONS: In contrast to some recent studies, we did not find
      significant associations between CA IX expression and tumor pO(2) levels or
      patient outcome in locally advanced carcinomas of the cervix. Probable
      explanations relate to the problems of sampling error using single biopsies and
      the existence of biological factors other than hypoxia that influence CA IX
      levels.

PMID- 14654551
TI  - Unfavorable prognostic factors associated with high frequency of microsatellite
      instability and comparative genomic hybridization analysis in endometrial cancer.
AB  - PURPOSE: Although many articles have been published regarding chromosomal
      instability (CI) and microsatellite instability (MI) in endometrial
      adenocarcinoma, the relationship between prognostic factors and the biological
      mechanisms accounting for genetic instability in these tumors has not yet been
      precisely defined. To do that, it will be necessary to clarify the molecular
      mechanisms involved in endometrial carcinogenesis. EXPERIMENTAL DESIGN: Tissue
      samples from 43 human primary endometrioid endometrial adenocarcinomas (EACs)
      were analyzed for CI and MI status using comparative genomic hybridization and 11
      microsatellite loci, respectively. Methylation status of the promoter of MLH1 was
      also determined. We analyzed all three of these parameters in relation to each
      other and to clinicopathological factors. RESULTS: Sixty-five percent of the EACs
      we examined had detectable CI. Frequent copy number gains were seen at 1q25-41
      (23%), 8q11.1-q21.1 (23%), 8q21.3-qter (21%); 28% of these tumors exhibited high
      frequency MI (MSI-H); Methylation of the MLH1 promoter was observed in 92% of
      EACs with MSI-H. Southern blotting showed amplification of MYCN in one tumor,
      which has been documented for the first time in a primary human EAC. CONCLUSIONS:
      MSI-H was correlated with histological grade, International Federation of
      Gynecologists and Obstetricians (FIGO) stage, myometrial invasion, and lymphonode
      metastasis. Our comparative genomic hybridization results demonstrated that the
      number of chromosomes involved in genomic alterations in EACs was distinctively
      fewer than those in other types of tumor. The carcinogenetic process leading to
      EAC appears to be highly complex; for example, MI and CI may act synergistically,
      whereas CI and/or MI are likely to be linked with tumor heterogeneity.

PMID- 14654552
TI  - Coexpression of insulin receptor-related receptor and insulin-like growth factor
      1 receptor correlates with enhanced apoptosis and dedifferentiation in human
      neuroblastomas.
AB  - PURPOSE: We compared the expression of the insulin receptor-related receptor
      (IRR) in primary human neuroblastomas with other biological and clinical
      parameters and the impact of its expression on prognostic outcome. EXPERIMENTAL
      DESIGN: We studied 49 neuroblastomas of different clinical stages and
      histological subtypes for (a) IRR, insulin-like growth factor 1 receptor (IGF
      1R), TrkA, p75 neurotrophin receptor, and MYCN mRNA expression by reverse
      transcription-PCR; (b) MYCN gene amplification by Southern blot analyses; (c)
      cyclin A protein expression by Western blot analyses indicating proliferation
      rate; and (d) apoptotic index (AI) by terminal deoxynucleotidyl transferase (Tdt)
      mediated dUTP nick end-labeling assay. RESULTS: IRR mRNA expression was found in
      25 (51%) neuroblastomas and correlated with stages 1, 2, 3, and 4S disease and
      with age </=12 months at diagnosis. IRR was expressed predominantly in
      neuroblastomas without MYCN gene amplification and coexpressed with IGF-1R, TrkA,
      and p75 neurotrophin receptor. IRR mRNA expression also correlated with an
      undifferentiated histology but not with the proliferation rate. In coexpression
      with IGF-1R, the IRR was associated with enhanced AI. IRR expression was
      significantly correlated with a good prognosis in all 49 neuroblastomas (6-year
      survival probability, 91.8% versus 49.7% for IRR nonexpression; P = 0.003).
      CONCLUSION: IRR expression is a new marker for a favorable prognosis in
      neuroblastoma that is independent of MYCN amplification and age at diagnosis. Our
      data suggest an influence of IRR on IGF signaling via IGF-1R because coexpression
      of these two receptor tyrosine kinases was significantly correlated with an
      undifferentiated histology, a high AI, and an advanced survival probability.

PMID- 14654553
TI  - Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in
      gastric carcinoma.
AB  - PURPOSE: A low expression level of cyclin-dependent kinase (Cdk) inhibitor p27 is
      associated with high aggressiveness and poor prognosis of various carcinomas.
      Human Cdk subunit 1 (Cks1), as well as S-phase kinase-associated protein 2
      (Skp2), is an essential and specific factor in the p27 proteolysis by SCF(Skp2)
      ubiquitin ligase. The purpose of this study is to clarify the clinical
      significance of Cks1 expression and the relationship between Cks1 and p27
      expression in gastric carcinomas. EXPERIMENTAL DESIGN: We measured Cks1
      expression using quantitative reverse transcription-PCR in 76 human gastric
      carcinomas and p27 expression using immunohistochemistry in 28 cases. Moreover,
      we established Cks1- and/or Skp2-transfected gastric carcinoma cell lines and
      assessed the relationship between Cks1, Skp2, and p27 expression using
      quantitative reverse transcription-PCR and Western blot analysis. RESULTS: Cks1
      high expression was correlated with poor prognosis (P < 0.05) and Cks1 expression
      was inversely correlated with the expression level of p27 protein in gastric
      carcinomas (P < 0.05). Using combined Skp2 data [T-a. Masuda, Cancer Res., 62:
      3819-3825, 2002], 88.9% of the Cks1/Skp2 double-high cases expressed a low level
      of p27 protein and showed the poorest prognosis (P < 0.05). Western blot analysis
      showed that Cks1/Skp2-cotransfected cells expressed a much lower level of p27
      protein than the controls. CONCLUSIONS: These findings indicate that Cks1, as
      well as Skp2, regulates the expression level of p27 protein in gastric
      carcinomas. Cks1 could play an important role in gastric carcinoma progression
      and would be a novel target for the treatment of gastric carcinomas as well as a
      strong prognostic marker.

PMID- 14654554
TI  - Association of serum adiponectin levels with breast cancer risk.
AB  - PURPOSE: Adiponectin is a peptide hormone secreted from the adipose tissue,
      affecting the proliferation and insulin sensitivity of various types of cells.
      Because association of obesity with breast cancer risk is well established, it is
      possible that adiponectin plays some role in the development of breast cancer.
      Thus, in the present study, the association of the serum adiponectin levels with
      breast cancer risk was investigated. EXPERIMENTAL DESIGN: A case-control study
      was conducted on 102 breast cancer patients (cases) and 100 healthy women
      (controls). The serum adiponectin levels of cases and controls were examined in
      their association with breast cancer risk after adjustment for the various
      classical risk factors (family history, age at menarche, parity, body mass index,
      and so forth). In addition, the relationship between the serum adiponectin levels
      and the various clinicopathological characteristics of breast cancers was
      studied. RESULTS: Women in the low tertile of serum adiponectin levels were
      associated with a significantly (P < 0.005) increased risk for breast cancer
      compared with women in the high tertile [odds ratio (OR), 3.63; 95% confidence
      interval (CI), 1.61-8.19]. Such an association was observed both in the
      premenopausal women (OR, 3.46; 95% CI, 0.89-13.50) and in the postmenopausal
      women (OR, 3.90; 95% CI, 1.23-12.44). The frequency of large (>2 cm) tumors and
      that of high histological grade (2+3) tumors were significantly (P < 0.005 and P
      < 0.05, respectively) higher in breast cancer patients in the low tertile of the
      serum adiponectin levels than those in the high and intermediate tertiles.
      CONCLUSIONS: These results suggest that the low serum adiponectin levels are
      significantly associated with an increased risk for breast cancer and that tumors
      arising in women with the low serum adiponectin levels are more likely to show a
      biologically aggressive phenotype. The association between obesity and breast
      cancer risk might be partly explained by adiponectin.

PMID- 14654555
TI  - Properties of bisphosphonates in the 13762 rat mammary carcinoma model of tumor
      induced bone resorption.
AB  - Bone metastasis from primary tumors is a clinically important complication of
      neoplastic progression. The role of parathyroid hormone-related protein (PTHrP)
      and transforming growth factor (TGF)-beta1 in this process has been clearly
      established. The current study describes an in vivo model of 13762 rat mammary
      carcinoma tumor cell-induced osteolysis in which PTHrP and TGF-beta1 expression
      is observed. Exposure of in vitro-cultured 13762 cells to doxorubicin, cis
      platinum, carboplatin, methotrexate, 5-fluorouracil, paclitaxel, alendronate,
      risedronate, or pamidronate for 72 h resulted in varying effects on cell
      proliferation (IC(50) values of 0.005, 0.4, 1.9, >40, 17.9, 0.003, >40, >40, and
      33.6 micro M, respectively). Tumor cells were implanted into the intramedullary
      space of the proximal tibia of rats, and the time course of tumor progression was
      evaluated using radiographic and microcomputed tomography scanning techniques.
      Trabecular bone mineral density, cortical bone mineral density, and whole bone
      mineral density were measured (in mg/cm(3)). In untreated animals, radiographic
      evidence of osteolysis was evident 7 days after implantation. Trabecular bone
      mineral density and whole bone mineral density were significantly decreased by 21
      days after implantation (48% and 26%, respectively). Bisphosphonates showed broad
      protective activity against tumor-driven osteolysis, Immunohistochemical
      evaluation of s.c. and intratibially implanted cells demonstrated the expression
      of PTHrP and TGF-beta1. The results of this study demonstrate the ability of
      13762 rat mammary carcinoma cells to elicit a measurable osteolysis and that
      bisphosphonates inhibit the tumor-induced bone resorption in this model.

PMID- 14654556
TI  - NLCQ-1 (NSC 709257): exploiting hypoxia with a weak DNA-intercalating
      bioreductive drug.
AB  - The development of weak DNA-intercalating bioreductive compounds is a new
      strategy to ensure DNA affinity high enough to produce toxicity yet low enough to
      permit efficient extravascular diffusion and penetration to hypoxic tumor tissue,
      as has been exemplified by the lead compound 4-[3-(2-nitro-1-imidazolyl)
      propylamino]-7-chloroquinoline hydrochloride (NLCQ-1, NSC 709257). Indeed,
      because of its weak DNA-binding, NLCQ-1 demonstrates significant hypoxic
      selectivity in several rodent and human tumor cell lines that can be increased up
      to 388-fold with 4.5 h exposure. In vitro reduction studies suggest that
      cytochrome P450 and b(5) reductases play a significant role in NLCQ-1
      bioreductive activation. NLCQ-1 synergistically enhances the effect of radiation
      against hypoxic cells in vitro and murine tumors in vivo and optimizes the effect
      of radioimmunotherapy in human xenografts. Importantly, NLCQ-1 substantially
      enhances, in a schedule-dependent manner, the antitumor effect of alkylating
      agents, as well as 5-fluorouracil and paclitaxel against murine tumors and human
      xenografts, without a concomitant enhancement in bone marrow or hypoxia-dependent
      retinal toxicity. In addition, NLCQ-1 exhibits good stability in human plasma and
      favorable pharmacokinetics in mice. The synthesis of NLCQ-1 has been successfully
      scaled-up and its excellent recovery from biological fluids has been established.
      Because of these results and the fact that NLCQ-1 compares favorably with the
      frontrunner, bioreductive compound tirapazamine, NLCQ-1 is about to enter a Phase
      I clinical trial.

PMID- 14654557
TI  - Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites,
      and causes dramatic vascular remodeling in an ovarian cancer model.
AB  - Ovarian cancer is the most lethal gynecological malignancy and the fifth most
      common cause of cancer in women. It is characterized by diffuse peritoneal
      carcinomatosis and often by large volumes of i.p. ascites. Because vascular
      endothelial growth factor (VEGF), also known as vascular permeability factor,
      increases vascular permeability and stimulates endothelial cell growth, its role
      in ovarian cancer has been evaluated in a number of studies. However, questions
      remain regarding the ability of VEGF alone to cause ascites formation and the
      ability of VEGF blockade to inhibit the growth of disseminated cancer. We have
      used retroviral technology to create cell populations that overproduce VEGF and
      report that enforced expression of VEGF by ovarian carcinoma cells dramatically
      reduces the time to onset of ascites formation. In fact, even tumor-free
      peritoneal overexpression of VEGF, created by using adenoviral vectors, is
      sufficient to cause ascites to accumulate. We have found that systemic
      administration of the VEGF-Trap, a recently described high-affinity soluble decoy
      receptor for VEGF, prevents ascites accumulation and also inhibits the growth of
      disseminated cancer. Remarkably, much as is observed in s.c. tumor models, VEGF
      blockade results in dramatic remodeling of the blood vessels in disseminated
      ovarian carcinoma. The potent effects of the VEGF-Trap in reducing both ascites
      and tumor burden suggest that it will be of value in a regimen for treatment of
      women with ovarian cancer and ascites.

PMID- 14654558
TI  - Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast
      cell tumors.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of the receptor
      tyrosine kinase inhibitor SU11654 on the activity of its molecular target KIT in
      canine mast cell tumors (MCT) and correlate target inhibition with mutational
      status of the c-kit juxtamembrane domain and SU11654 plasma concentration.
      EXPERIMENTAL DESIGN: Tumor biopsies were obtained from dogs with advanced MCTs
      before and 8 h after administration of a single oral dose of SU11654, previously
      shown to be active in dogs with MCTs. Blood samples were taken to determine the
      plasma concentration of SU11654. Levels of phosphorylated KIT and ERK1/2 were
      assessed in tumor biopsies by Western blot. Tumors were analyzed by PCR for the
      presence or absence of an internal tandem duplication (ITD) in the juxtamembrane
      domain of c-kit. RESULTS: Fourteen dogs with advanced MCTs were enrolled in the
      study; 11 of these were evaluable for KIT target modulation (the remaining tumor
      specimens had inevaluable amounts of total KIT protein). Of these, eight MCTs
      showed reduced levels of phosphorylated KIT relative to total KIT after treatment
      with SU11654, compared with pretreatment biopsies. All four evaluable MCTs
      expressing ITD mutant c-kitshowed modulation of KIT phosphorylation, as did four
      of seven tumors expressing non-ITD c-kit. Phosphorylated ERK1/2 was modulated in
      seven tumors; this did not correlate with inhibition of KIT phosphorylation
      CONCLUSION: SU11654 treatment at the efficacious dose results in inhibition of
      KIT phosphorylation in canine MCTs.

PMID- 14654559
TI  - Protein geranylgeranylation is critical for the regulation of survival and
      proliferation of lymphoma tumor cells.
AB  - PURPOSE: Prenylation is essential for membrane localization and participation of
      proteins in various signaling pathways. The following study was conducted to
      examine the importance of protein farnesylation and geranylgeranylation for the
      regulation of lymphoma cell survival and proliferation. EXPERIMENTAL DESIGN:
      Lymphoma cells were treated with the beta-hydroxy-beta-methylglutaryl-CoA
      reductase inhibitor lovastatin, which inhibits protein farnesylation and
      geranylgeranylation by the depletion of intracellular pools of
      farnesylpyrophosphate and geranylgeranylpyrophosphate. In addition, farnesyl
      transferase and geranylgeranyl transferase activities were specifically inhibited
      by FTI-277 and GGTI-298, respectively. RESULTS: Only inhibition of
      geranylgeranylation by lovastatin led to reduction of cell viability in lymphoma
      cell lines and purified tumor cells from lymphoma patients in a time- and dose
      dependent way. Reduction in the number of viable cells was mediated by both
      induction of apoptosis and inhibition of proliferation. In addition, GGTI-298 was
      more effective in induction of apoptosis and inhibition of proliferation than FTI
      277. Apoptosis induced by inhibition of protein geranylgeranylation was
      associated with a reduction of Mcl-1 protein levels, collapse of the
      mitochondrial transmembrane potential, and caspase-3 activation. Inhibition of
      proliferation resulted from the induction of G(1) arrest. Furthermore, lovastatin
      at low concentrations sensitized lymphoma cells to dexamethasone, including cells
      resistant to this drug. CONCLUSION: These results indicate that protein
      geranylgeranylation is critical for the regulation of lymphoma tumor cell
      survival and proliferation and that pharmacological agents such as lovastatin or
      geranylgeranyl transferase inhibitors, alone or in combination with other drugs,
      may be useful in the treatment of lymphoma.

PMID- 14654560
TI  - Histone deacetylase inhibitors induce growth suppression and cell death in human
      rhabdomyosarcoma in vitro.
AB  - PURPOSE: A group of histone deacetylase inhibitors has been shown to be effective
      in suppressing the growth of a variety of transformed cell lines in vitro and in
      vivo. The effects of two of these agents, suberoylanilide hydroxamic acid (SAHA)
      and suberoyl-3-aminopyridineamide hydroxamic acid (pyroxamide), were investigated
      for their growth-suppressive effects on rhabdomyosarcoma (RMS) cells.
      EXPERIMENTAL DESIGN AND RESULTS: Dose-response experiments of two RMS cell lines,
      RD (embryonal) and RH30B (alveolar), were performed with SAHA (0.25-3.0 micro M)
      and pyroxamide (1.25-20.0 micro M). Both agents caused a dose-dependent decrease
      in viable cell number and an increase in percentage of dead cells over time.
      Exposure of the RMS cells to SAHA and pyroxamide resulted in an accumulation of
      acetylated histones with increasing doses by Western blot analysis. Additionally,
      there was an induction of p21/WAF1 at 15 and 24 h when the cells were cultured
      with SAHA (2.0 micro M) or pyroxamide (20.0 micro M), concentrations that were
      tested because they successfully induced inhibition of cell growth and initiated
      cell death in both RMS cell lines. An increase in nuclei with hypodiploid or sub
      G(1) fraction was found by flow cytometry with increasing doses of both SAHA
      (0.25-3.0 micro M) and pyroxamide (1.25-20.0 micro M) over time. This finding is
      consistent with DNA fragmentation and cell death by apoptosis. CONCLUSIONS: SAHA
      and pyroxamide induce growth suppression and cell death in human RMS in vitro.
      Accumulation of acetylated histones and induction of p21/WAF1 expression are
      observed in cells exposed to either agent.

PMID- 14654561
TI  - Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of acetyl-L
      carnitine.
AB  - PURPOSE: Antineoplastic drugs belonging to platinum or taxane families are
      severely neurotoxic, inducing the onset of disabling peripheral neuropathies with
      different clinical signs. Acetyl-L-carnitine (ALC) is a natural occurring
      compound with a neuroprotective activity in several experimental paradigms. In
      this study we have tested the hypothesis that ALC may have a protective role on
      cisplatin and paclitaxel-induced neuropathy. EXPERIMENTAL DESIGN: Sensory nerve
      conduction velocity (SNCV) was measured in rats before, at end, and after an
      additional follow-up period from treatments with cisplatin, paclitaxel, or with
      the respective combination with ALC. In addition, serum from treated animals was
      collected to measure the levels of circulating NGF, and left sciatic nerves were
      processed for light and electron microscope observations. ALC interference on
      cisplatin and paclitaxel antitumor activity and protective mechanisms were
      investigated using several in vitro and in vivo models. RESULTS: ALC cotreatment
      was able to significantly reduce the neurotoxicity of both cisplatin and
      paclitaxel in rat models, and this effect was correlated with a modulation of the
      plasma levels of NGF in the cisplatin-treated animals. Moreover, experiments in
      different tumor systems indicated the lack of interference of ALC in the
      antitumor effects of cisplatin and paclitaxel. The transcriptional profile of
      gene expression in PC12 cells indicated that ALC, in the presence of NGF, was
      able to positively modulate NGFI-A expression, a gene relevant in the rescue from
      tissue-specific toxicity. Finally, the transcriptionally ALC-mediated effects
      were correlated to increase histone acetylation. CONCLUSION: In conclusion, our
      results indicate that ALC is a specific protective agent for chemotherapy-induced
      neuropathy after cisplatin or paclitaxel treatment without showing any
      interference with the antitumor activity of the drugs.

PMID- 14654562
TI  - Manganese superoxide dismutase expression correlates with chemosensitivity in
      human gastric cancer cell lines.
AB  - PURPOSE: The purpose is to investigate the potential correlation between
      antioxidant enzyme (AOE) levels and resistance to anticancer drugs in human
      gastric carcinoma cell lines. EXPERIMENTAL DESIGN: Protein contents of AOEs such
      as manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase,
      catalase, glutathione S-transferase-pi, p-glycoprotein, and multidrug resistance
      associated protein were observed by Western blot analysis, and MnSOD activity was
      measured in six Korean gastric cancer cell lines. The direct correlation between
      AOEs and the chemosensitivity to doxorubicin (DOX), mitomycin C, 5-fluorouracil,
      and vinblastine was analyzed by cytotoxicity test. MnSOD was overexpressed by
      transient transfection of human MnSOD cDNA. RESULTS: Expressions of AOEs in
      gastric cancer cell lines were variable. MnSOD expression was related with the
      resistance to DOX and mitomycin C but not with that to 5-fluorouracil and
      vinblastine. In comparison, expressions of other AOEs, p-glycoprotein and
      multidrug resistance-associated protein, were not correlated with tumor
      sensitivity to any of the drugs used. Cell lines with a high MnSOD protein
      content showed higher MnSOD activity than those with a low MnSOD protein content.
      In addition, MnSOD overexpression increased the resistance of gastric carcinoma
      cells to DOX. CONCLUSIONS: MnSOD is an important factor of drug response to
      reactive oxygen species-generating anticancer drugs in the gastric cancer cells.
      Thus, measurement of MnSOD levels in clinical samples may provide an indication
      of subsequent treatment response of gastric cancer patients.

PMID- 14654563
TI  - Immunomodulation in established murine tumors: response and survival rate
      enhancement by blood leukocyte-augmenting substance 236 (Cl-), a novel synthetic
      compound.
AB  - Immunomodulation in cancer has obvious appeal. Available data suggest the central
      role to be played by the host immune response in cancer outcome. Herein, we
      report a novel compound, Blood Leukocyte Augmenting Substance 236 (Cl(-)) [BLAS
      236 (Cl(-))], which is able to restore and/or strengthen immunocompetence, which
      is critical in host-resistance to malignancy. The effects of several protocols in
      which BLAS 236 (Cl(-)) was given as single-agent or combined therapy on
      established murine tumors were evaluated in terms of long-term tumor-free
      survivors (>1 year). Treatment significantly improved overall complete response
      and survival rates and prolonged the life span of mice to beyond that of animals
      receiving placebo. The most outstanding protocols (denoted B3, B6 and D6, D7),
      were able to flatten tumor-free survival curves at the 80% and 100% levels,
      respectively (P < 0.001 for each protocol); these results compare favorably with
      those reported for other preclinical trials. Immunomodulation by BLAS 236 (Cl(-))
      is viewed as a new efficient, safe way of potentiating and maintaining host
      resistance to malignancy that holds promise as an adjuvant therapy alternative to
      current immune approaches for the ultimate cure of cancer.

PMID- 14654564
TI  - Trans-tissue, sustained release of gemcitabine from photocured gelatin gel
      inhibits the growth of heterotopic human pancreatic tumor in nude mice.
AB  - PURPOSE: Although gemcitabine, a deoxycytidine analogue, recently demonstrated
      improvements in the response rate for pancreatic cancer, the median survival for
      patients is limited to 4-6 months. The purpose of the present study was to
      develop trans-tissue delivery of gemcitabine, which is based on photocured
      gelatin gel immobilized with gemcitabine, and to validate whether such a system
      inhibits the growth of the pancreatic tumor in vivo. EXPERIMENTAL DESIGN: The in
      vitro release profile of gel-embedded gemcitabine from a gel was examined based
      on in vitro chemosensitivity of AsPC1 cell (human pancreatic cancer cell line)
      for gemcitabine. The permeation of gel-embedded rhodamine B (used as a model
      drug) into tissues and inhibitory effect of tumor growth of photocured gelatin
      gel immobilized with gemcitabine were examined using in vivo s.c. tumor model of
      athymic mice. RESULTS: The release profile was characterized as an initial burst
      of release, followed by a gradual release, irrespective of gelatin concentration.
      Rhodamine B permeated into the tumor and retained for at least 10 days.
      Photocured gelatin gel immobilized with gemcitabine significantly reduced the
      tumor volume compared with gemcitabine injection. Therapeutic success was
      correlated with decreased cell proliferation and increased cell apoptosis in
      tumor cells, supported by proliferating cell nuclear antigen and terminal
      deoxynucleotidyltransferase-mediated nick end labeling staining. Blood analysis
      and body weight measurement showed that little side effect was observed in this
      therapy. CONCLUSIONS: In situ trans-tissue gemcitabine delivery on the tissue
      with possibly remnant cancer cells using the drug-releasing matrix developed here
      is expected to reduce the rate of local recurrence for patients with pancreatic
      cancer.

PMID- 14654565
TI  - Preclinical evaluation of 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic
      acid as a modulator of etoposide in human Waldenstrom's macroglobulinemia
      xenograft model.
AB  - We have previously reported that XK469 (2-[4-(7-chloro-2-quinoxalinyloxyphenoxy]
      propionic acid) enhances topo IIalpha expression in WSU-WM cells in vitro [E.
      Mensah-Osman et al., Mol. Cancer Ther., 1: 1321-1326, 2002]. To test the
      hypothesis that XK469-induced expression of topo IIalpha sensitizes WSU-WM cells
      to the topo IIalpha inhibitor etoposide (VP-16), we investigated the antitumor
      effects of XK469 and VP-16 in vivo, using the WSU-WM SCID xenograft model.
      Individual dosages of XK469 at 20-60 mg/kg/injection i.v. for a maximum-tolerated
      dose of 240 mg/kg were achievable in SCID mice. Simultaneous administration of a
      subtherapeutic dose of XK469 (20 mg/kg) and VP-16 at its maximum-tolerated dose
      of 15 mg/kg proved to be highly toxic and lethal. However, daily sequential
      treatment of XK469 given i.v. via tail vein at 20 mg/kg for a total of 120 mg/kg,
      followed 7 h later by VP-16 i.p. at 15 mg/kg for a total of 90 mg/kg, had no
      significant toxicity in SCID mice. The sequential treatment was associated with
      enhanced antitumor activity. Tumor growth inhibition T/C, tumor growth delay T-C,
      and log(10) kill for XK469 alone were 61%, 3 days and 0.46; VP-16 alone 6%, 12
      days and 1.83, respectively; whereas the sequential administration of both agents
      gave a T/C value of 0%, T-C value of 23 days and a log(10) kill of 3.5. On the
      basis of these animal results, we conclude that the sequential treatment of WSU
      WM tumors with XK469 and VP-16 was highly active. The study supports our in vitro
      observation that XK469 potentiates VP-16 activity. The sequential use of both
      agents resulted in clinically significant antitumor activity in the WM model.

PMID- 14654570
TI  - Management of childhood constipation.
AB  - The effective management of constipation in childhood requires an understanding
      of the ways that the physical and psychological factors interact. The early
      difficulty with defecation that leads to pain, fear, and refusal to use the pot
      or lavatory often progresses to the formation of vicious cycles of increasing
      faecal retention as the rectum increases in capacity and the experience of
      passing large, hard stools is repeated. There is increasing distress as overflow
      faecal incontinence compounds the problem for the older child. The medical,
      psychological, and surgical management strategies are reviewed together with the
      rationale for their use.

PMID- 14654569
TI  - Tropical chronic pancreatitis.
AB  - Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non
      alcoholic pancreatitis, seen almost exclusively in the developing countries of
      the tropical world. The classical triad of TCP consists of abdominal pain,
      steatorrhoea, and diabetes. When diabetes is present, the condition is called
      fibrocalculous pancreatic diabetes (FCPD) which is thus a later stage of TCP.
      Some of the distinctive features of TCP are younger age at onset, presence of
      large intraductal calculi, more aggressive course of the disease, and a high
      susceptibility to pancreatic cancer. Pancreatic calculi are the hallmark for the
      diagnosis of TCP and in non-calcific cases ductal dilation on endoscopic
      retrograde cholangiopancreatography, computed tomography, or ultrasound helps to
      identify the disease. Diabetes is usually quite severe and of the insulin
      requiring type, but ketosis is rare. Microvascular complications of diabetes
      occur as frequently as in type 2 diabetes but macrovascular complications are
      uncommon. Pancreatic enzyme supplements are used for relief of abdominal pain and
      reducing the symptoms related to steatorrhoea. Early diagnosis and better control
      of the endocrine and exocrine dysfunction could help to ensure better survival
      and improve the prognosis and quality of life of TCP patients.

PMID- 14654571
TI  - Education of senior house officers: current challenges.
AB  - Over recent years several factors have impacted upon the education of doctors in
      training in medicine and other specialties. These factors include the European
      Working Time Directive and shift patterns of working, increasing service demands,
      changes in the examination and assessment processes, and clinical governance
      issues. In addition, over the next few years further changes will take place with
      the implementation of "Modernising Medical Careers" document and the
      establishment of the new Postgraduate Medical Education and Training Board. This
      article attempts to review the effects of these changes on education of junior
      doctors and to suggest some possible ways to address these challenges.

PMID- 14654573
TI  - Chronic non-malignant musculoskeletal pain in older adults: clinical issues and
      opioid intervention.
AB  - Musculoskeletal pain is common, frequently under-reported, and inadequately
      treated in the older adult. The objective of this article is to review the
      management of musculoskeletal pain syndromes in older adults emphasising the
      potential role of opioid agents in carefully selected patients. Systematic
      analysis of the relevant literature was done. Even in cognitively impaired
      patients, assessment of musculoskeletal pain is mandatory. An algorithm for
      musculoskeletal pain is presented emphasising a stepwise pharmacological approach
      in combination with an array of non-pharmacological therapies. Comorbid
      conditions may limit therapeutic choices, particularly in the elderly. Repeated
      assessment of pain levels as well as functional status is critical for optimal
      pain management.

PMID- 14654574
TI  - Drug therapy in chronic heart failure.
AB  - Chronic heart failure is widely recognised as a common and escalating problem
      that causes major disability and often shortens life. Diuretics and digoxin have
      formed the mainstay of treatment for many years. Clinical trials have
      demonstrated that angiotensin converting enzymes and beta-blockers, in selected
      patients, improve symptoms and reduce mortality. Angiotensin-II antagonists and
      spironolactone may also have a role in certain individuals. Newer pharmacological
      approaches to the management of this complex disease are being developed, but
      await full evaluation.

PMID- 14654575
TI  - Prostate cancer management: 2. An update on locally advanced and metastatic
      disease.
AB  - Just under half of men with prostate cancer present with locally advanced or
      metastatic disease. A multidisciplinary approach is required to improve survival,
      minimise complications, and provide adequate palliation. Radiotherapy remains the
      mainstay of treatment for pelvic disease control and encouraging results have
      been reported with androgen ablation as adjuvant therapy. In metastatic disease
      androgen ablation is usually first line, although ultimately most tumours become
      hormone refractory, requiring second or third line treatments. Localised or
      systemic radiotherapy may be used for palliation in metastatic disease. With the
      advent of more potent bisphosphonates the common bony complications associated
      with metastases may be reduced. This, the second review of prostate cancer,
      explores the various treatments available to the multidisciplinary team.

PMID- 14654576
TI  - An industry based approach to colorectal cancer screening in an asymptomatic
      population.
AB  - The uptake of faecal occult blood testing in a workplace based colorectal cancer
      screening programme was investigated. Altogether 1828 employees aged 41-65 years
      at a large British industrial company were invited to receive a free faecal
      occult blood test (Haemoccult). Faecal occult blood tests were completed on three
      separate days. Patients with positive results were invited to undergo
      colonoscopy. The number of employees completing kits was measured and differences
      in compliance according to age, sex, and occupation were tested with a chi2 test.
      Compliance was 25.4%, and similar in men (25.0%) and women (32.0%, chi2=3.0, not
      significant). In men, compliance was highest in those aged 51-60 years (30.5%
      chi2>1.6, p<0.001). Compliance in women aged 41-50 years, 51-60 years, and 61-65
      years was similar (Yates's corrected chi2<2.08, not significant). Managers
      returned more kits than clerical and blue collar workers (28.6% v 23.5%,
      chi2=5.6, p<0.02). One percent of tests were positive and one patient had a
      tubular adenoma. Compliance in employees aged 51-60 years was comparable to that
      achieved in one-off British general practice programmes, but less than that in
      the large randomised trial of screening in general practices in Nottinghamshire.
      Health education of large numbers of people is easier at the workplace than in
      the community. Future screening must target older employees and those with
      clerical and blue collar jobs.

PMID- 14654577
TI  - Acceptability of oesophagogastroduodenoscopy without intravenous sedation:
      patients' versus endoscopist's perception with special reference to older
      patients.
AB  - BACKGROUND: Unsedated oesophagogastroduodenoscopy (OGD) is considered by most
      endoscopists to be a quick, safe, and well tolerated procedure. Older patients
      are said to tolerate it better than younger patients. However, patients'
      perception of the discomfort for the unsedated OGD has not been well studied.
      OBJECTIVE: This study was undertaken to compare (1) patients' perception of
      discomfort with the endoscopist's perception of patients' discomfort for the
      unsedated OGD, (2) tolerability between older (> or =75 years) and younger (<75
      years) patients. DESIGN AND SUBJECTS: A total of 130 consecutive patients
      attending a day case endoscopy unit were recruited for the study. The patients
      and endoscopist recorded their assessment using a visual analogue scale (VAS).
      The results were analysed using non-parametric tests. Thirty patients were
      excluded from the study based on exclusion criteria. Sixty three (57%) patients
      were aged > or =75 years and 37 (43%) were <75 years. RESULTS: A significant
      difference was noted between patients' perception of the discomfort and the
      endoscopist's assessment of the patient's discomfort as suggested by the overall
      higher VAS scores for patients (median 4.9, SD 2.6) than those of the endoscopist
      (median 2.2, SD 1.2), giving a significant difference in median VAS score of 3.4
      (p<0.001). Older and younger patients had similar scores, with median (SD) VAS
      scores of 4.8 (2.5) for > or =75 years and 4.9 (2.8) for <75 years. The
      endoscopist's median scores for these two groups were 2.2 (1.2) and 2.1 (1.3),
      respectively. CONCLUSIONS: Patients' discomfort during OGD performed without
      sedation was greatly underestimated by the endoscopist. There was no significant
      difference in acceptability between old and the young patients.

PMID- 14654578
TI  - Completion of the audit cycle: standardised nurse-led information for patients.
AB  - BACKGROUND: It is increasingly accepted that patients want information about
      their proposed treatment, and that provision of such information may alleviate
      fear and may improve the process of obtaining informed consent. It is not yet
      clear what form such information should take. OBJECTIVE: Based on differences
      shown previously between patients receiving standard treatment and those in
      clinical trials, a system of routine appointments with a chemotherapy nurse at
      least one day before the patient offered consent to treatment was established for
      all patients receiving chemotherapy in Leicestershire, at which time patients
      were given standardised written information regarding outpatient chemotherapy and
      specific drugs. METHOD: In order to complete the audit cycle, the previous
      questionnaire study was repeated. RESULTS: From 160 questionnaires distributed,
      131 complete replies were received. Compared with the previous audit, a
      significantly higher proportion of patients receiving standard chemotherapy
      remembered being given written information about chemotherapy from a nurse before
      starting their treatment and remembered signing a consent form. The significant
      difference in feelings of involvement in the decision to have chemotherapy
      between patients receiving standard chemotherapy and those in clinical trials
      detected in the previous audit was no longer detectable, suggesting the clinical
      effectiveness of the intervention performed. CONCLUSION: Implementation of nurse
      led appointments with provision of standardised information before formal consent
      being taken should be studied further for its potential to improve patients'
      involvement in medical decision making.

PMID- 14654579
TI  - From trench fever to endocarditis.
AB  - The case of a 44 year old woman with infective endocarditis due to Bartonella
      quintana, an organism long recognised to cause a condition known as trench fever,
      is reported. This case illustrates the lengthy differential diagnosis of "culture
      negative" endocarditis. In addition the presence of serological cross reactivity
      of Bartonella spp and Chlamydia spp demonstrates the potential for misdiagnosis
      in these circumstances.

PMID- 14654580
TI  - Sinoatrial block complicating legionnaire's disease.
AB  - A 59 year old woman presented with acute onset of fever, chills, diaphoresis,
      vague chest discomfort, and was found to be hypotensive and tachypnoeic. An
      electrocardiogram demonstrated sinoatrial block with a junctional rhythm between
      50 and 80 beats/min. All cultures were negative and imaging studies unrevealing.
      Her urine tested positive for Legionella pneumophila antigen serotype 1 and she
      improved with antibiotic therapy.

PMID- 14654581
TI  - Aborted sudden death in a young male.

PMID- 14654582
TI  - An unusual cause of abdominal pain.

PMID- 14654583
TI  - An unusual case of relapsing Graves' disease.

PMID- 14654584
TI  - A case of severe, unexplained breathlessness.

PMID- 14654589
TI  - Annual summary of vital statistics--2002.
AB  - The crude birth rate in 2002 was 13.9 births per 1000 population, the lowest ever
      reported for the United States. The number of births, the crude birth rate, and
      the fertility rate (64.8) all declined slightly (by 1% or less) from 2001 to
      2002. Fertility rates were highest for Hispanic women (94.0), followed by black
      (65.4), Asian or Pacific Islander (63.9), Native American (58.0), and non
      Hispanic white women (57.5). Fertility rates declined slightly for all
      race/ethnic groups from 2001 to 2002. The birth rate for teen mothers continued
      to fall, dropping 5% from 2001 to 2002 to 42.9 births per 1000 women aged 15 to
      19 years, another record low. The teen birth rate has fallen 31% since 1991;
      declines were more rapid for younger teens aged 15 to 17 (40%) than for older
      teens aged 18 to 19 (23%). The proportion of all births to unmarried women
      remained approximately the same at one third. Smoking during pregnancy continued
      to decline; smoking rates were highest among teen mothers. In 2002, 26.1% of
      births were delivered by cesarean section, up 7% since 2001 and 26% since 1996.
      The primary cesarean rate has risen 23% since 1996, whereas the rate of vaginal
      birth after a previous cesarean delivery has fallen 55%. The use of timely
      prenatal care increased slightly to 83.8% in 2002. From 1990 to 2002, the use of
      timely prenatal care increased by 6% (to 88.7%) for non-Hispanic white women, by
      24% (to 75.2%) for black women, and by 28% (to 76.8%) for Hispanic women, thus
      narrowing racial disparities. The percentage of preterm births rose to 12.0% in
      2002, from 10.6% in 1990 and 9.4% in 1981. Increases were largest for non
      Hispanic white women. The percentage of low birth weight (LBW) births also
      increased to 7.8% in 2002, up from 6.7% in 1984. Twin and triplet/+ birth rates
      both increased by 3% from 2000 to 2001. Multiple births accounted for 3.2% of all
      births in 2001. The infant mortality rate (IMR) was 6.9 per 1000 live births
      (provisional data) in 2002 compared with 6.8 in 2001 (final data). The ratio of
      the IMR among black infants to that for white infants was 2.5 in 2001, the same
      as in 2000. Racial differences in infant mortality remain a major public health
      concern. The role of LBW in infant mortality remains a major issue. New
      Hampshire, Utah, and Massachusetts had the lowest IMRs. State-by-state
      differences in IMR reflect racial composition, the percentage of LBW, and birth
      weight-specific neonatal mortality rates for each state. The United States
      continues to rank poorly in international comparisons of infant mortality.
      Expectation of life at birth reached a record high of 77.2 years for all sex and
      race groups combined in 2001. Death rates in the United States continue to
      decline. Between 2000 and 2001, death rates declined for the 3 leading causes of
      death: diseases of the heart, malignant neoplasms, and cerebrovascular diseases.
      Death rates for children ages 1 to 19 years decreased for unintentional injuries
      by 3.3% in 2001; the death rate for chronic lower respiratory diseases decreased
      by 25% in 2001. Cancer and suicide levels did not change for children ages 1 to
      19. A large proportion of childhood deaths continue to occur as a result of
      preventable injuries.

PMID- 14654590
TI  - Bullying among young adolescents: the strong, the weak, and the troubled.
AB  - OBJECTIVES: Bullying and being bullied have been recognized as health problems
      for children because of their association with adjustment problems, including
      poor mental health and more extreme violent behavior. It is therefore important
      to understand how bullying and being bullied affect the well-being and adaptive
      functioning of youth. We sought to use multiple data sources to better understand
      the psychological and social problems exhibited by bullies, victims, and bully
      victims. DESIGN, SETTING, AND PARTICIPANTS: Analysis of data from a community
      sample of 1985 mostly Latino and black 6th graders from 11 schools in
      predominantly low socioeconomic status urban communities (with a 79% response
      rate). MAIN OUTCOME MEASURES: Peer reports of who bullies and who is victimized,
      self-reports of psychological distress, and peer and teacher reports of a range
      of adjustment problems. RESULTS: Twenty-two percent of the sample was classified
      as involved in bullying as perpetrators (7%), victims (9%), or both (6%).
      Compared with other students, these groups displayed school problems and
      difficulties getting along with classmates. Despite increased conduct problems,
      bullies were psychologically strongest and enjoyed high social standing among
      their classmates. In contrast, victims were emotionally distressed and socially
      marginalized among their classmates. Bully-victims were the most troubled group,
      displaying the highest level of conduct, school, and peer relationship problems.
      CONCLUSIONS: To be able to intervene with bullying, it is important to recognize
      the unique problems of bullies, victims, and bully-victims. In addition to
      addressing these issues directly with their patients, pediatricians can recommend
      school-wide antibullying approaches that aim to change peer dynamics that support
      and maintain bullying.

PMID- 14654591
TI  - Does presentation format at the Pediatric Academic Societies' annual meeting
      predict subsequent publication?
AB  - OBJECTIVE: The validity of research presented at scientific meetings continues to
      be a concern. Presentations are chosen on the basis of submitted abstracts, which
      may not contain sufficient information to assess the validity of the research.
      The objective of this study was to determine 1) the proportion of abstracts
      presented at the annual Pediatric Academic Society (PAS) meeting that were
      ultimately published in peer reviewed journals; 2) whether the presentation
      format of abstracts at the meeting predicts subsequent full publication; and
      whether the presentation format was related to 3) the time to full publication or
      4) the impact factor of the journal in which research is subsequently published.
      METHODS: We assembled a list of all abstracts submitted to the PAS meetings in
      general pediatrics categories in 1998 and 1999, using both CD-ROM and journal
      publications. In each year, we chose up to 80 abstracts from each presentation
      format ("publish only," "poster," "poster symposium," "platform presentation").
      We chose either 1) all abstracts in each format or 2) when there were >80
      abstracts, a random selection of 80 of them. We assessed each selected abstract
      for subsequent full publication by searching Medline in March 2003; if published,
      then we recorded the journal, month, and year of publication. We used logistic
      and linear regression to determine whether publication, time to publication, and
      the journal's impact factor were associated with the abstract's presentation
      format. RESULTS: Overall, 44.6% of abstracts presented at the PAS meeting
      achieved subsequent full publication within 4 to 5 years. There were significant
      differences between the rates of subsequent full publication of abstracts
      submitted but not chosen for presentation at the meeting (22.2%) and those that
      were chosen for presentation in poster sessions (40.0%), poster symposia (44.1%),
      and platform presentations (53.8%). There were no meaningful differences between
      the presentation formats in their mean time to publication and their mean journal
      impact factor. CONCLUSIONS: PAS meeting attendees and the press should be
      cautious when interpreting the presentation format of an abstract as a predictor
      of either its subsequent publication in a peer-reviewed journal or the impact
      factor of the journal in which it will appear.

PMID- 14654592
TI  - Proficiency of pediatric residents in performing neonatal endotracheal
      intubation.
AB  - OBJECTIVE: Current guidelines of the Accreditation Council for Graduate Medical
      Education have restricted the amount of intensive care experience obtained during
      pediatric residency. The impact on performing procedures has not been evaluated.
      To determine the current level of competency in 1 common procedure, we
      investigated the proficiency of pediatric residents in performing neonatal
      endotracheal intubation during the academic years 1998-1999 and 2000-2001.
      METHODS: Indication for intubation, number of attempts, and achievement of
      success were recorded by the respiratory therapist present for the procedure.
      Each intubation was scored according to the attempt on which intubation was
      successful. Indications for intubation were categorized as respiratory failure,
      delivery room resuscitation, and meconium-stained amniotic fluid. Competency was
      defined as a successful intubation occurring on the first or second attempt
      >or=80% of the time. Intubation scores were compared between residents at various
      stages of training and analyzed by multivariate logistic regression analysis for
      significance. Comparisons were then performed to determine percentage success
      with confidence intervals. We also surveyed previous graduates of the training
      program not included in the observations for this study and asked them to
      indicate how frequently they perform intubation in current practice and to assess
      their own competence in the procedure. RESULTS: A total of 449 resident
      procedures were observed during the study periods: 192 by postgraduate year 1
      (PGY-1) residents, 126 by PGY-2 residents, and 131 by PGY-3 residents. A total of
      35% (160 of 449) of intubation procedures were never successful by pediatric
      house officers. Intubation was successful on the first or second attempt for 50%
      of PGY-1 residents (95% confidence interval [CI]: 42.6-56.8), 55% of PGY-2
      residents (95% CI: 46-63.5), and 62% of PGY-3 residents (95% CI: 53.9-70.7). The
      third-year residents exhibited a significantly higher likelihood of performing a
      successful intubation compared with first-year residents. The first-year
      residents in 1998-1999 showed no improvement by their third year in 2000-2001.
      Surveys were sent to 56 graduates of our residency program (1998-2000). Completed
      surveys were received from 31 (66%) of 47. A total of 71% of the respondents are
      practicing general pediatrics, and 36% attend deliveries or perform intubations.
      A total of 87% reported that their level of confidence with endotracheal
      intubation was good or excellent after completion of residency training.
      CONCLUSIONS: We provide objective and subjective data concerning the proficiency
      of pediatric residents in performing neonatal endotracheal intubation. None of
      our resident groups met the specified definition of technical competence,
      although there was improvement with advancing training level in bivariate
      analyses. However, graduates of our training program felt confident with their
      intubation skills in contrast to our objective findings. As exposure to these
      important skills becomes limited, methods to ensure attainment of technical
      competency during training may need to be redefined.

PMID- 14654593
TI  - Screening for retinoblastoma: presenting signs as prognosticators of patient and
      ocular survival.
AB  - OBJECTIVE: To correlate 3 common presenting signs of retinoblastoma with patient
      and ocular survival and to assess the efficacy of current pediatric screening
      practices for retinoblastoma. METHODS: A retrospective study was conducted of
      1831 retinoblastoma patients from our center (1914-June 2000). Patient survival
      (excluding deaths from other primary neoplasms) and ocular survival (presenting
      eyes) rates were calculated and analyzed using the Kaplan-Meier method. RESULTS:
      Leukocoria correlated with excellent patient survival (>86%, 5 years) but poor
      ocular survival in unilateral (4%, 5 years) and bilateral patients (29%, 5
      years). A total of 308 (19%) of 1654 patients presented with strabismus: patient
      survival was excellent (90%, 5 years), and ocular survival was poor (17%, 5
      years) yet better than leukocoria. Patients who had a family history of
      retinoblastoma and were clinically screened for retinal tumors from birth were
      diagnosed younger (8 months of age) and earlier (Reese Ellsworth group 1 = 26
      [58%] of 45) and had better ocular survival than nonscreened patients with a
      family history. More patients were initially detected by family/friends (1315
      [80%] of 1632) than pediatricians (123 [8%] of 1632) or ophthalmologists (156
      [10%] of 1632). CONCLUSION: Most US children whose retinoblastoma is diagnosed
      initially present with leukocoria detected by a parent, despite routine pediatric
      screening for leukocoria via the red reflex test. Initial disease detection at
      the point of leukocoria or strabismus correlated with high patient survival rates
      and poor ocular survival rates for the presenting eye. Saving eyes and vision
      requires disease recognition before leukocoria, as demonstrated by the better
      ocular salvage rate among patients who had a positive family history and received
      clinical surveillance via early, routine dilated funduscopic examinations by an
      ophthalmologist.

PMID- 14654594
TI  - Changes in globus pallidus with (pre)term kernicterus.
AB  - OBJECTIVE: We report serial magnetic resonance (MR) and sonographic behavior of
      globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the
      clinical context in very low birth weight preterm infants. On the basis of this
      information, we suggest means of diagnosis and prevention. METHODS: Charts and MR
      and ultrasound images of 5 preterm infants and 3 term infants with suspected
      bilirubin-associated brain damage were reviewed. Included were preterm infants
      with severe hearing loss, quadriplegic hypertonia, and abnormal hypersignal of
      globus pallidus on T2-weighted MR imaging (MRI). In 1 infant who died on day 150,
      the diagnosis was confirmed during the neonatal period. The others were picked up
      as outpatients and scanned at 12 or 22 months' corrected age. Three instances of
      term kernicterus were included for comparison of serial MRI in the neonatal
      period and early infancy: they were caused by glucose-6-phosphate dehydrogenase
      deficiency, urosepsis, and dehydration plus fructose 1-6 biphosphatase
      deficiency. RESULTS: Five preterm infants of 25 to 29 weeks' gestational age
      presented with total serum bilirubin (TSB) levels below exchange transfusion
      thresholds commonly advised. Mixed acidosis was present in 3 infants around the
      TSB peak. The bilirubin/albumin molar ratio was >0.5 in all, in the absence of
      displacing drugs. All failed to pass bedside hearing screen tests and had severe
      hearing loss on auditory brain response testing. Symmetrical homogeneous
      hyperechogenicity of globus pallidus was the alerting feature in 1 infant. Globus
      pallidus was hyperintense on T1-weighted MR images in this child. The other
      infants presented with severe developmental delay as a result of dyskinetic
      quadriplegia and hearing loss. Globus pallidus was normal on T1- but hyperintense
      on T2-weighted MR images at 12 or 22 months' corrected age. Subthalamic
      involvement was documented in coronal fluid attenuated inversion recovery MRI in
      2 infants. The term infants with classical clinical presentation in the neonatal
      period had MR behavior similar to the preterms, but pallidal injury was not
      recognized with targeted sonographic examination. Their neonatal MR images
      demonstrated pallidal T1 hyperintensity and mild T2 hyperintensity. CONCLUSION:
      Acidotic very low birth weight preterm infants with low serum albumin levels
      develop MR-confirmed pallidal injury and hearing loss facing "accepted" TSB
      levels. Serial MRI documents a shift from acute mainly T1 hypersignal to
      permanent T2 hypersignal in globus pallidus within the late neonatal period.
      Subthalamic and not thalamic involvement helps to differentiate from ischemic or
      metabolic disorder. As newborns, these infants are rigid and have severe apnea,
      before developing hypertonic quadriplegia in infancy.

PMID- 14654595
TI  - Management of hyperbilirubinemia in newborns: measuring performance by using a
      benchmarking model.
AB  - BACKGROUND: Accreditors hold hospitals accountable for harm from serious newborn
      hyperbilirubinemia, yet standards for evaluating performance in prevention are
      lacking. OBJECTIVE: We confirmed prognostic variables for newborn
      hyperbilirubinemia and developed a benchmarking model for self-evaluation of
      hyperbilirubinemia management. METHODS: We conducted a 3-year prospective cohort
      study in the Henry Ford Health System (HFHS) on 5507 healthy newborns of >or=35
      weeks' gestational age. HFHS follows a rigorous protocol for hyperbilirubinemia
      management. Defining hyperbilirubinemia as age-specific levels of total serum
      bilirubin exceeding American Academy of Pediatrics criteria for considering
      phototherapy and severe hyperbilirubinemia as total serum bilirubin >or=20 mg/dL,
      we used logistic and Poisson regressions to determine predictors and estimate
      parameters for a benchmarking model. We compared incidence rates for severe
      hyperbilirubinemia from HFHS to aggregate data from 11 hospitals reported to have
      less rigorous management. RESULTS: Newborns were 52.9% black, 14.4% white, 24.3%
      Latino, and 2.4% Asian; 30% were exclusively and 28% partially breastfed.
      Regression analyses revealed associations for hyperbilirubinemia and severe
      hyperbilirubinemia with black mothers (negative) and exclusive or partial
      breastfeeding and younger gestational age (positive). Male newborns and older
      mothers were also associated with severe hyperbilirubinemia. For all 5 variables,
      we found a lower risk for severe hyperbilirubinemia at HFHS than in the
      comparison hospital group. To compare hospitals, we developed a benchmarking
      model for incidence of hyperbilirubinemia adjusting for race, feeding method, and
      gestational age. CONCLUSIONS: Hospitals with access to newborns' inpatient and
      postdischarge data can use our benchmarking model to compare their management of
      hyperbilirubinemia with a reference population that received rigorous care.

PMID- 14654596
TI  - Fatal pulmonary hypertension associated with pertussis in infants: does
      extracorporeal membrane oxygenation have a role?
AB  - OBJECTIVE: The deaths of 4 infants who had confirmed pertussis infection at our
      hospital during the past year motivated us to review their cases as well as the
      use of extracorporeal membrane oxygenation (ECMO) in respiratory failure caused
      by pertussis. METHODS: Retrospective chart reviews of the 4 infants who had
      pertussis and died at Vanderbilt University Medical Center (VUMC) from May 2001
      to May 2002 were conducted. The Extracorporeal Life Support Organization (ELSO)
      database is an international voluntary registry established in 1986 to compile
      passive reports of adult and pediatric patients placed on ECMO. We searched this
      database for pertussis cases and analyzed the clinical outcomes by age,
      ventilatory management, and measurements of cardiopulmonary status. RESULTS: All
      4 infants who died from pertussis infection at VUMC were younger than 3 months
      and had severe pulmonary hypertension, and ECMO therapy was considered for
      respiratory failure. Review of the international ELSO database, focusing only on
      children from 1986 to July 2002, revealed a total of 23,970 patients placed on
      ECMO. Since the first pertussis case treated with ECMO in 1990, a total of 61
      children with pertussis have been treated with ECMO, representing an increase
      from 0.09% to 1% of the total cases. Mean age of the pertussis patients placed on
      ECMO was 88 days (1 day-2.7 years). The overall mortality was 70.5% (43 of 61)
      but was significantly higher for infants who were younger than 6 weeks (84%)
      compared with infants who were older than 6 weeks (61%). When evaluating pre-ECMO
      management, survivors had received significantly higher mean positive end
      expiratory pressures than nonsurvivors (11.1 +/- 4.5 vs 7.3 +/- 3.1 cmH(2)O) and
      had significantly higher serum pH than nonsurvivors (7.31 +/- 0.14 vs 7.14 +/-
      0.19). There was no effect of duration of ECMO, positive inspiratory pressure,
      mean arterial pressure, ECMO mode (venoarterial vs venovenous mode), or sex on
      mortality. CONCLUSIONS: Although the ECMO registry is not an active surveillance
      system, it suggests that the numbers of children who require ECMO for pertussis
      have significantly increased. The high fatality rates of pertussis patients who
      have placed on ECMO are alarming and should stimulate reevaluation of whether
      this high-risk intervention is beneficial to patients with pertussis. This
      review, coupled with the 4 infants who died of pertussis at VUMC, suggests that
      improved measures are needed to prevent pertussis in infants.

PMID- 14654597
TI  - Evaluation of a rapid urine antigen assay for the detection of invasive
      pneumococcal disease in children.
AB  - OBJECTIVE: Streptococcus pneumoniae remains the most common cause of occult
      bacteremia, bacterial pneumonia, and meningitis in young febrile children. We
      sought to determine the utility of a pneumococcal urine antigen assay among young
      febrile children at varying risk of invasive pneumococcal disease. METHODS: We
      prospectively enrolled 5 groups of children, 3 months to 5 years of age, who
      presented to an urban pediatric emergency department or hospital-based clinic
      between January 1, 2000, and April 1, 2001. The groups enrolled included 1)
      children with pneumococcal bacteremia, 2) febrile children with pneumonia, 3)
      febrile nonbacteremic children with leukocytosis, 4) febrile nonbacteremic
      children with normal white blood cell (WBC) counts, and 5) afebrile children with
      no evidence of current or recent bacterial infection. RESULTS: Of 346 children
      enrolled, positive assay results were found in 23 (95%) of 24 with pneumococcal
      bacteremia (95% confidence interval [CI]: 77%-100%), 47 (76%) of 62 with lobar
      pneumonia (95% CI: 63%-85%), 28 (15%) of 181 nonbacteremic children with fever
      (95% CI: 11%-22%) with no difference among patients with elevated WBC counts
      (18%; 95% CI: 11%-27%) compared with those with normal WBC counts (11%; 95% CI:
      5%-21%), and 6 of 79 patients without fever (8%; 95% CI: 3%-16%). CONCLUSIONS:
      This S pneumoniae antigen detection assay demonstrated high sensitivity for
      proven (bacteremic) and suspected (focal pneumonia) invasive pneumococcal
      infections. The rate of false-positive test results among febrile children
      without identified pneumococcal infection is approximately 15%. Although not
      ideal, this combination of sensitivity and specificity compares favorably with
      other available tests, such as the WBC or absolute neutrophil count used to
      screen children for clinically unsuspected pneumococcal infections.

PMID- 14654598
TI  - Ventilator-associated pneumonia in extremely preterm neonates in a neonatal
      intensive care unit: characteristics, risk factors, and outcomes.
AB  - OBJECTIVE: To determine the rates, characteristics, risk factors, and outcomes of
      ventilator-associated pneumonia (VAP) in extremely preterm neonates in a neonatal
      intensive care unit (NICU). METHODS: A prospective cohort study was conducted at
      the St Louis Children's Hospital on all patients who had birth weight <or=2000 g
      and were admitted to the NICU for >or=48 hours from October 2000 to July 2001.
      Extremely preterm neonates were defined as neonates with estimated gestational
      age (EGA) <28 weeks. The primary outcome was the development of VAP. Secondary
      outcomes were death and NICU length of stay (LOS). Multiple logistic regression
      was performed to determine independent predictors for VAP and mortality. RESULTS:
      A total of 229 patients were enrolled. Sixty-seven (29%) had EGA <28 weeks.
      Nineteen episodes of VAP occurred in 19 (28.3%) of 67 mechanically ventilated
      patients. VAP rates were 6.5 per 1000 ventilator days for patients with EGA <28
      weeks and 4 per 1000 ventilator days for EGA >or=28 weeks. By multivariate
      analysis, bloodstream infection before VAP (adjusted odds ratio: 3.5; 95%
      confidence interval [CI]: 1.2-10.8) was an independent risk factor for VAP after
      adjustment for the duration of endotracheal intubation. Ventilator-associated
      pneumonia (adjusted odds ratio: 3.4; 95% CI: 1.2-12.3) was an independent
      predictor of mortality. A strong association between VAP and mortality was
      observed in neonates who stayed in the NICU >30 days (relative risk: 8.0; 95% CI:
      1.9-35.0). Patients with VAP also had prolonged NICU LOS (median: 138 vs 82
      days). CONCLUSIONS: VAP occurred at high rates in extremely preterm neonates and
      was associated with increased mortality. Additional studies are needed to develop
      interventions to prevent VAP in NICU patients.

PMID- 14654599
TI  - The impact of preterm birth on hospital inpatient admissions and costs during the
      first 5 years of life.
AB  - OBJECTIVES: To compare the cumulative use and cost of hospital inpatient services
      to 5 years of age by individuals divided into 4 subgroups by gestational age at
      birth. DESIGN: Costs applied to the hospital service utilization profile of each
      infant born in 2 areas covered by the Oxford Record Linkage Study during 1970
      1993. SETTING: Oxfordshire and West Berkshire, southern United Kingdom. SUBJECTS:
      239 694 individuals divided into 4 subgroups by gestational age at birth: <28
      weeks, 28 to 31 weeks, 32 to 36 weeks, >or=37 weeks. MAIN OUTCOME MEASURES:
      Number and duration of hospital admissions during the first 5 years of life and
      costs, expressed in pound sterling and valued at 1998-1999 prices, of hospital
      inpatient services. RESULTS: The total duration of hospital admissions for
      infants born at <28 and at 28 to 31 gestational weeks was 85 and 16 times that
      for term infants, respectively, once duration of life had been taken into
      account. Hospital inpatient service costs were significantly higher for preterm
      infants than for term infants, with the cost differences persisting throughout
      infancy and early and mid-childhood. Over the first 5 years of life, the adjusted
      mean cost difference was estimated at pound 14,614 ( 22,798 US dollars) when
      infants born at <28 weeks gestational age were compared with term infants and
      pound 11,958 ( 18,654 US dollars) when infants born at 28 to 31 weeks gestational
      age were compared with term infants. Independent contributions to total cost came
      from being born: small for gestational age, a multiple, during the 1970s and
      early 1980s, to a woman of extreme maternal age or who was hospitalized
      antenatally, and from experiencing extended survival or childhood disease.
      However, preterm birth remained the strongest predictor of high cost.
      CONCLUSIONS: Preterm birth is a major predictor of how much an individual will
      cost hospital service providers during the first 5 years of life.

PMID- 14654600
TI  - A comparison of on-site and off-site patent ductus arteriosus ligation in
      premature infants.
AB  - INTRODUCTION: Persistent patent ductus arteriosus (PDA) often produces
      hemodynamic and respiratory derangement necessitating use of inotropic drugs and
      escalating ventilatory support in premature infants. When medical therapy fails,
      surgical ligation is indicated. Because of the risks of transferring unstable
      neonates to the operating room, ductal ligation is routinely performed at the
      neonatal intensive care unit (NICU) bedside. Some patients, however, require
      transfer from hospitals without pediatric cardiac surgical teams. In an attempt
      to eliminate the risks associated with transfer, a surgical team from our
      institution offered to perform duct ligation in the NICUs of referring
      institutions. This experienced team consisted of a pediatric cardiac attending
      anesthesiologist and certified registered nurse anesthetist, cardiac operating
      room nurses, an attending cardiothoracic surgeon, and a cardiothoracic surgery
      fellow. We retrospectively reviewed our experience. METHODS: After approval from
      the Committee for the Protection of Human Subjects, the charts of premature
      neonates who underwent PDA ligation in the NICU at the Children's Hospital of
      Philadelphia NICU or in a network NICU between January 1996 and April 2002 were
      reviewed. Data abstracted included institution, gender, gestational age, birth
      weight, weight at surgery, and number of courses of indomethacin. Mean arterial
      blood pressure and use of inotropic drugs and ventilatory parameters (fraction of
      inspired oxygen, peak inspiratory pressure) were recorded at the time of surgery
      and 96 hours postoperatively. Perioperative complications were recorded. RESULTS:
      Seventy-two patients met the criteria for inclusion. PDA ligation was performed
      in the Children's Hospital of Philadelphia NICU in 38 of 72 patients, 53% (group
      1). The remainder, 34 of 72 (47%) underwent PDA ligation in the NICU at 1 of 6
      referring institutions (group 2). There were no significant differences between
      groups with respect to demographics, number of courses of indomethacin, or use of
      inotropic drugs or ventilatory support. The incidence of perioperative
      complications did not differ between groups: 3 in group 1 (bleeding, chylothorax,
      and pleural effusion) and 3 in group 2 (pneumothorax [3]). There were no
      anesthetic-related complications. Seven patients died (4 in group 1 and 3 in
      group 2), none within 96 hours of surgery and none secondary to the procedure.
      DISCUSSION: The data demonstrate that an experienced team can perform PDA
      ligation safely in NICUs of hospitals without on-site pediatric cardiac surgical
      capabilities in critically ill neonates without incurring the risks inherent in
      patient transport. Most importantly, patient care is continued by the neonatology
      team most familiar with the infant's medical and social history, and the
      patient's family is minimally inconvenienced.

PMID- 14654601
TI  - Postreduction management of intussusception in a children's hospital emergency
      department.
AB  - OBJECTIVE: To evaluate the current management of patients with intussusception
      who have undergone successful reduction by contrast enema in a tertiary care
      children's hospital. To compare differences in the incidence of recurrence and
      adverse events between those patients who were hospitalized after enema reduction
      and those who were observed in the emergency department (ED). METHODS: This was a
      retrospective cohort study of children 0 to 18 years of age who underwent
      uncomplicated enema reduction for intussusception. Hospitalization versus ED
      observation management were compared for length of stay, incidence of recurrence,
      and adverse events. RESULTS: One hundred twenty-three children were identified
      with an International Classification of Diseases, Ninth Revision code for
      intussusception. Of those, 106 patients (86%) had an enema reduction attempted.
      Three had a normal enema and were given the diagnosis of "resolved
      intussusception." Eighty-three (80%) of the patients had a successful reduction.
      Seventy-eight (94%) of those patients had no preexisting condition and had
      complete medical records. Of those 78 patients, 27 (35%) were hospitalized and 51
      (65%) were observed in the ED. The mean length of hospitalization was 22.7 hours
      (range: 10-50 hours), and the mean length of ED observation was 7.2 hours (range:
      0-21 hours). Eleven recurrences were observed in 8 of these 78 patients (10%
      recurrence rate). Four patients in the hospitalized group and 4 patients in the
      ED observation group had recurrences (5 hours-10.9 months). Four of the 8
      patients had a recurrence within the first 48 hours. All first recurrences
      occurred after the patient had been discharged from the hospital or ED
      observation unit. No adverse events occurred in any of the patients who had a
      successful initial reduction (95% confidence interval [0%-4.6%]). CONCLUSIONS:
      The postreduction management of intussusception is variable at our institution.
      Previously healthy patients who have undergone successful enema reductions are
      unlikely to have adverse outcomes. Postreduction observation in the ED or the
      hospital does not seem to affect outcomes in this clinical setting.

PMID- 14654602
TI  - Prevalence of blood lead levels >or= 5 micro g/dL among US children 1 to 5 years
      of age and socioeconomic and demographic factors associated with blood of lead
      levels 5 to 10 micro g/dL, Third National Health and Nutrition Examination
      Survey, 1988-1994.
AB  - OBJECTIVES: As part of an investigation into the impact of a potential revision
      in federal childhood lead poisoning prevention policy that would result in
      screening children for blood lead levels (BLLs) >or=5 micro g/dL rather than the
      current 10 micro g/dL, we analyzed the most recent available, nationally
      representative data to identify prevalence of BLLs >or=5 micro g/dL and
      socioeconomic and demographic characteristics of 1- to 5-year-old children with
      BLLs >or=5 but <10 micro g/dL. METHODS: We performed statistical analyses on data
      from the Third National Health and Nutrition Examination Survey (NHANES III)
      (1988-1994) to describe trends in BLLs >or=5 micro g/dL overall and among
      subpopulations of children <6 years old and to compare risk factors for falling
      within 1 of 3 groups of children (those with BLLs >or=5 but <10 micro g/dL;
      >or=10 but <20 micro g/dL; and >or=20 micro g/dL) using the group reported as 0.7
      to <5 micro g/dL as the referent. RESULTS: Overall prevalence of BLLs >or=5 micro
      g/dL among 1- to 5-year-old children was 25.6%, although most (76%) of these
      children had BLLs <10 micro g/dL. Children with BLLs >or=5 micro g/dL included
      46.8% of non-Hispanic black children, 27.9% of Mexican American children, and
      18.7% of non-Hispanic white children; 42.5% of children in housing built before
      1946, 38.9% of children in housing built between 1946 and 1973, and 14.1% of
      children in housing built after 1973 had BLLs >or=5 micro g/dL. Compared with non
      Hispanic white children, non-Hispanic black children were 3 times more likely to
      have a BLL >or=5 but <10 micro g/dL, 7 times more likely to have a BLL of 10-20
      micro g/dL, and 13.5 times more likely to have a BLL >or=20 micro g/dL. Similar
      increases in the association between risk factor and BLL were seen with respect
      to other known risk factors including age of housing, region of the country, and
      poverty. CONCLUSIONS: The high prevalence of BLLs >or=5 micro g/dL overall and
      within US subpopulations will be an important variable in any change in screening
      and intervention criteria. However, most children with BLLs >or=5 micro g/dL are
      below the current intervention level of 10 micro g/dL. Exposure to lead from
      multiple sources is suggested by the prevalence of BLLs >or=5 micro g/dL but <10
      micro g/dL among children with uncertain risk factors. The probable presence of
      one or more known risk factors for childhood lead poisoning increases as BLL
      increases.

PMID- 14654603
TI  - Generalist-subspecialist communication for children with chronic conditions: a
      regional physician survey.
AB  - OBJECTIVE: To identify target areas for interventions to improve communication
      between pediatric generalists (PCPs) and pediatric subspecialists (SPs) in the
      outpatient care of children with chronic conditions. METHODS: We constructed a 4
      page mailed questionnaire probing communication practices, opinions about the
      role of communication in care, and perceived barriers and facilitators to PCP-SP
      communication in the care of children with chronic conditions. In the spring of
      2001, we surveyed all 495 New England SPs who were members of the American
      Academy of Pediatrics (AAP) and/or SP societies and a random sample of 495
      generalist AAP members in New England. Eligible were those actively providing
      outpatient care. Most items were rated on a 5-point scale. RESULTS: Of those
      eligible, 48% (412/860) completed the questionnaire. Although 98% of respondents
      agreed that communication was important for good care, reported practices
      reflected large gaps in this area. Frequent receipt (>60% of the time) of
      communication about an initial referral was reported by only 28% of SPs. Barriers
      reported as most important involved inefficiencies in telephone contact,
      transcription delay, and failure to keep all providers informed when >1
      specialist is involved. Important facilitators included letters or phone calls at
      or before the time of consultation, and clear and specific referral questions
      from PCPs. PCPs saw communication as more of a problem than did SPs (40% vs 28%),
      and reported several barriers as more important. Although 86% of respondents had
      access to e-mail in their practices, <20% used it often. CONCLUSIONS: PCPs and
      SPs sharing care for children with chronic conditions are troubled by their
      frequent failure or inability to contact their colleagues by phone and letter.
      PCPs communicate less frequently than SPs yet perceive more problems with
      communication. Interventions to promote efficient contact between providers at or
      before the time of subspecialty visits can lead to improved coordination of care,
      which in turn may better meet the needs of families.

PMID- 14654604
TI  - Impact of television viewing patterns on fruit and vegetable consumption among
      adolescents.
AB  - BACKGROUND: National data indicate that children and youth do not meet Healthy
      People 2010 objectives for fruit and vegetable intake. Television viewing is
      hypothesized as a contributing factor because of its documented role in
      encouraging consumption of highly advertised foods that may lead to the
      replacement of fruits and vegetables. METHODS: A sample of 548 ethnically diverse
      students (average age: 11.7 +/- 0.8 years) from public schools in 4 Massachusetts
      communities were studied prospectively over a 19-month period from October 1995
      to May 1997. We examined the associations between baseline and change in hours of
      television and video viewing per day (the predictor variables) and change in
      energy-adjusted intake of fruits and vegetables by using linear regression
      analyses to control for potentially confounding variables and the clustering of
      observations within schools. FINDINGS: For each additional hour of television
      viewed per day, fruit and vegetable servings per day decreased (-0.14) after
      adjustment for anthropometric, demographic, dietary variables (including baseline
      percent energy from fat, sit-down dinner frequency, and baseline energy-adjusted
      fruit and vegetable intake), and physical activity. Baseline hours of television
      viewed per day was also independently associated with change in fruit and
      vegetable servings (-0.16). CONCLUSIONS: Television viewing is inversely
      associated with intake of fruit and vegetables among adolescents. These
      associations may be a result of the replacement of fruits and vegetables in
      youths' diets by foods highly advertised on television.

PMID- 14654605
TI  - Impact of zinc supplementation on diarrheal morbidity and growth pattern of low
      birth weight infants in kolkata, India: a randomized, double-blind, placebo
      controlled, community-based study.
AB  - OBJECTIVE: To assess the impact of zinc supplementation on diarrheal morbidity
      and growth pattern of low birth weight (LBW) infants. METHODOLOGY: In a
      randomized, double-blind, placebo-controlled, community-based study conducted in
      the Tiljala slum of eastern Kolkata, India, between 1999 and 2001, a birth cohort
      of 100 LBW infants was randomly allocated into either an intervention group
      receiving 1 mL daily dose of 5 mg of elemental zinc as zinc sulfate in vitamin B
      complex-based syrup or a placebo group receiving an identical placebo of 1 mL of
      vitamin-based syrup from birth up to 1 completed year of age. Active weekly
      surveillance was conducted for detection of diarrhea. Anthropometric measurements
      of each child were recorded once every month as close to the child's birth date
      as possible. Data were analyzed by using statistical software packages SPSSPC+
      4.0 (SPSS, Inc, Chicago, IL) and Epi Info 6.0 (Centers for Disease Control and
      Prevention, Atlanta, GA). RESULTS: Among the zinc-supplemented group, diarrheal
      incidence of 1.36 episodes per child per year were observed, whereas it was 1.93
      episodes per child per year among the placebo group, giving a relative risk of
      1.4 (95% confidence interval: 1.02-2.00). Linear growth and weight for age showed
      significant differences between the supplemented and placebo groups only at the
      end of 1 year. Interestingly, the impact of zinc supplementation was masked to a
      large extent by the protective action of breastfeeding. CONCLUSIONS: The study
      showed that zinc supplementation had a beneficial impact on the incidence of
      diarrhea and also weight gain among LBW infants.

PMID- 14654606
TI  - Corrected end-tidal carbon monoxide closely correlates with the corrected
      reticulocyte count in coombs' test-positive term neonates.
AB  - OBJECTIVE: To evaluate clinical usefulness of corrected end-tidal carbon monoxide
      (ETCOc) measurements in healthy, term, Coombs' test-positive neonates and
      correlate it to the corrected reticulocyte count (RC). METHODS: ETCOc and RC were
      determined (at 36 +/- 12 hours of age) in 50 Coombs' test-positive neonates and
      compared with the ETCOc values of 50 Coombs' test-negative neonates. RESULTS:
      Fifty percent of Coombs' test-positive infants had RCs <5% (within a normal range
      for a healthy newborn) and ETCOc = 1.8 +/- 0.34 parts per million (ppm) and
      likely did not exhibit hemolysis. Among infants with elevated RCs, 72% had RCs
      between 5% and 8% and ETCOc = 2.77 +/- 0.68 ppm, and 28% had RCs >8% and ETCOc =
      4.52 +/- 0.83 ppm. There was an almost linear correlation (r = 0.86) between the
      RC and the ETCOc among Coombs' test-positive infants. The 50 Coombs' test
      negative infants had ETCOc = 1.6 +/- 0.45 ppm. Serial ETCOc measurements were
      performed in 14 Coombs' test-positive infants: in all but 1 infant ETCOc values
      declined over time. CONCLUSIONS: There is a good correlation between ETCOc and RC
      in Coombs' test-positive infants. ETCOc >2.5 ppm predicts a significant elevation
      of RC in 90% of Coombs' test-positive infants.

PMID- 14654607
TI  - Not only a matter of epilepsy: early problems of cognition and behavior in
      children with "epilepsy only"--a prospective, longitudinal, controlled study
      starting at diagnosis.
AB  - OBJECTIVE: To understand early educational and behavioral predicament in
      childhood "epilepsy only." METHODS: A multicenter, prospective, longitudinal
      study was conducted of 51 outpatient schoolchildren with newly diagnosed
      idiopathic or cryptogenic epilepsy and 48 sex-matched classmate control subjects.
      All children underwent neuropsychological assessment 3 times within the first
      year after diagnosis; parents and teachers completed behavior questionnaires, and
      patients' parents were interviewed to inventory contextual adversity. Principal
      components analysis of cognition and behavior disclosed 6 major components that
      were related with the interview data (repeated measures analysis of variance).
      RESULTS: Despite similar intelligence and educational background, significantly
      more patients (51%) than control subjects (27%) required special educational
      assistance. Patients obtained worse scores across components of cognition and
      behavior. Parents and teachers perceived patients to have more behavioral
      problems. Differences between groups existed at pretreatment baseline. Over time,
      notwithstanding stable percentages of poor scores in both groups, nonpersistence
      of poor scores was impressive (each time other children scored poorly in other
      domains). Rather than epilepsy characteristics, contextual adversities were
      significant risk factors. CONCLUSION: Already in the earliest stage of the
      illness, children with epilepsy are liable to vicissitudes in cognitive and
      behavioral functioning. Contextual variables are all-important.

PMID- 14654608
TI  - Long-term results of pediatric cardiac surgery in Finland: education, employment,
      marital status, and parenthood.
AB  - OBJECTIVE: This population-based study was designed to examine the psychosocial
      outcome of Finnish patients who had been operated on for congenital heart disease
      during childhood. METHODS: A questionnaire was mailed to 3789 adult patients who
      had been operated on for congenital heart defects in Finland. Of these, 2896
      (76%) answered the questionnaire. The mean age of patients was 33 years (range:
      18-59 years), and they had had their first operation 9 to 46 years earlier.
      RESULTS: The patients had coped well with their defects when compared with the
      general Finnish population. The educational level of patients was comparable to
      and employment level was higher than expected (70% vs 66%, respectively). They
      were living in a steady relationship as often as the general population, but the
      number of parents among the patients was lower than that expected (47% vs 49%,
      respectively). The incidence of congenital heart disease among the 2697 children
      of the patients was 2.4%. CONCLUSION: Our results confirm that in addition to
      high survival rate, the long-term psychosocial outcome of patients with
      surgically treated congenital heart defects is good if they do not have any
      additional syndromes that cause mental retardation.

PMID- 14654609
TI  - Cost-effectiveness of inhaled nitric oxide in the treatment of neonatal
      respiratory failure in the United States.
AB  - OBJECTIVE: Two recent randomized controlled trials (RCTs) reported that inhaled
      nitric oxide (iNO) decreased the incidence of extracorporeal membrane oxygenation
      (ECMO) or death in term and near-term newborns with hypoxic respiratory failure.
      Our objective was to estimate the cost-effectiveness ratio of iNO in this
      population. METHODS: We studied 1000 simulation cohorts (n = 483 for each cohort)
      of term/near-term newborns with hypoxemic respiratory failure. We conducted our
      study following US Public Health Service Panel on Cost-Effectiveness in Health
      and Medicine guidelines, adopting the US societal perspective. We constructed a
      decision tree reflecting iNO use, subsequent ECMO use, death, and long-term
      neurologic and respiratory morbidity in survivors, as determined from the
      combined outcomes of the 2 RCTs (n = 483). We estimated costs on the basis of
      length-of-stay data for the initial episode of care from 1 of the RCTs, unit
      costs from administrative data sets, and current pricing for iNO. We ran a Monte
      Carlo simulation to generate estimates of differences in costs and effects at 1
      year, along with the stochastic uncertainty around these estimates. We expressed
      effects as quality-adjusted survival, assuming quality of life = 1 with no
      comorbidity, 0.7 with 1 comorbidity, and 0.49 (0.7 x 0.7) with 2 comorbidities.
      We constructed a base case, in which iNO was initiated at tertiary care ECMO
      centers (mimicking the RCTs) and a Public Health Service Panel on Cost
      effectiveness in Health and Medicine reference case, in which iNO was initiated
      at the local hospital before transfer (mimicking real-world practice). We exposed
      our assumptions to a sensitivity analysis. RESULTS: Direct application of the
      trial results (base case) suggested that iNO was both more effective and cheaper
      (cost savings of 1880 dollars per case despite acquisition costs of 5150 dollars,
      predominantly as a result of decreased need for ECMO), with 84.6% probability
      that the cost-effectiveness ratio was better than 100,000 dollars per quality
      adjusted life-year. Under the reference case, iNO was also more effective (though
      slightly less so) and was even cheaper (cost savings of 4400 dollars per case),
      with 71.6% probability that iNO was cheaper and more effective and 91.6%
      probability that the cost effectiveness ratio was better than 100,000 dollars per
      quality-adjusted life-year. Sensitivity analyses showed these estimates to be
      sensitive to patient selection and the price of iNO but insensitive to
      assumptions regarding quality of life. CONCLUSIONS: From a US societal
      perspective, iNO has a favorable cost-effectiveness profile when initiated either
      at ECMO centers or at local hospitals in term/near-term neonates with hypoxemic
      respiratory failure.

PMID- 14654610
TI  - A novel mutation in the anion exchanger 1 gene is associated with familial distal
      renal tubular acidosis and nephrocalcinosis.
AB  - OBJECTIVE: The anion exchanger gene (AE1) or band 3 encodes a chloride
      bicarbonate (Cl(-)/HCO(3)(-)) exchanger expressed in the erythrocyte and in the
      renal alpha-intercalated cells involved in urine acidification. The purpose of
      the present study was to screen for mutations in the AE1 gene in 2 brothers (10
      and 15 years of age) with familial distal renal tubular acidosis (dRTA),
      nephrocalcinosis, and failure to thrive. METHODS: AE1 mutations were screened by
      single-strand conformation polymorphism, cloning, and sequencing. RESULTS: A
      complete form of dRTA was confirmed in the 2 affected brothers and an incomplete
      form in their father. All 3 were heterozygous for a novel 20-bp deletion in exon
      20 of the AE1 gene. This deletion resulted in 1 mutation in codon 888 (Ala-888-
      >Leu) followed by a premature termination codon at position 889, truncating the
      protein by 23 amino acids. As band 3 deficiency might lead to spherocytic
      hemolytic anemia or ovalocytosis, erythrocyte abnormalities were also
      investigated, but no morphologic changes in erythrocyte membrane were found and
      the osmotic fragility test was normal. CONCLUSIONS: A novel mutation in the AE1
      gene was identified in association with autosomal dominant dRTA. We suggest that
      RTA be considered a diagnostic possibility in all children with failure to thrive
      and nephrocalcinosis.

PMID- 14654611
TI  - Importance of parental conceptual model of illness in severe recurrent abdominal
      pain.
AB  - OBJECTIVES: Recurrent abdominal pain (RAP) affects up to 15% of children. A
      biopsychosocial approach to the treatment of children with RAP has been proposed
      as an alternative to the traditional medical model. The aim of this study was to
      examine whether the parental conceptual model of illness is a factor in the long
      term outcome of children with severe RAP. METHODS: The study was undertaken in 2
      parts: 1) a review of the medical and psychiatric records (including Child
      Behavior Checklist [CBCL]) of all children with RAP of sufficient severity to
      necessitate hospitalization during a 5-year period and 2) a structured telephone
      interview to collect information on ongoing abdominal pain, other somatic
      symptoms, school attendance, and the parents' opinion as to the cause of the
      child's pain. RESULTS: Twenty-eight of 30 children who were identified were
      available for follow-up. Twenty-three (82%) were tertiary referrals from other
      pediatric services, and 20 had pain for >6 months. On admission 7 (25%) of 28 had
      a depressive disorder, and 8 (29%) had an anxiety/depressive disorder. Twenty-one
      of 28 parents completed the CBCL, and on analysis of the CBCL, 11 (52%) children
      had scores in the clinical range (>65). At follow-up (mean: 3.56 years; standard
      deviation: 1.59), 14 (50%) of 28 continued to complain of pain. These children
      also complained of multiple other somatic complaints and had repeated school
      absences. Only 1 (7%) of 14 parents of children with ongoing pain believed that
      there was a psychological cause for their child's pain, whereas 11 (78%) of 14
      parents of the children who had recovered believed that the cause was
      attributable to psychological factors (odds ratio: 47.67; 95% confidence
      interval: 3.56-1511.6). CONCLUSIONS: The acceptance by parents of a
      biopsychosocial model of illness is important for the resolution of recurrent
      abdominal pain in children.

PMID- 14654612
TI  - Do needs drive services use in young children?
AB  - OBJECTIVE: To determine whether different factors predicted parental recognition
      of mental health problems in children and use of services for those problems and
      to determine whether mental health problems elicit service use in the same way as
      physical health or developmental problems. METHODS: Survey of the parents of an
      age- and sex-stratified random sample of children who were born in 1 Connecticut
      hospital selected from state birth records. RESULTS: Logistic regression results
      demonstrate that a number of child and family factors are related to problem
      recognition, defined as thinking about seeking services and/or talking to a
      professional about a problem. However, factors related to the third outcome of
      interest-service use-are more limited and include only physical health and
      developmental problems, parental worry about language, and family conflict.
      Furthermore, mental health problems were not discussed with professionals, and
      they were not associated with receipt of services at the same rates as physical
      health or developmental problems. CONCLUSIONS: The correlates of problem
      recognition (defined as thinking about seeking services or actually speaking to a
      professional about a problem) differ from those of service use, and, whereas
      mental health, physical health, and developmental problems all affect problem
      recognition, mental health problems do not result in service use. Furthermore,
      rates of service use vary dramatically across the 3 categories. These results
      suggest that needs alone do not drive service use. Rather, other factors may
      influence which needs are met.

PMID- 14654613
TI  - Evidence assessment of the accuracy of methods of diagnosing middle ear effusion
      in children with otitis media with effusion.
AB  - OBJECTIVES: We report the findings of an evidence assessment on the accuracy of
      methods of diagnosing middle ear effusion in children with otitis media with
      effusion (OME). METHODS: We searched Medline (1966-January 2000), the Cochrane
      Library (through January 2000), and Embase (1980-January 2000) and identified
      additional articles from reference lists in proceedings, published articles,
      reports, and guidelines. Excluded were nonhuman studies; case reports;
      editorials; letters; reviews; practice guidelines; non-English-language
      publications; and studies on patients with immunodeficiencies, craniofacial
      anomalies (including cleft palate), primary mucosal disorders, or genetic
      conditions. From each eligible study, we calculated the sensitivity, specificity,
      positive predictive value, negative predictive value, accuracy, and prevalence of
      OME in the cohort. We determined the number of studies for each comparison of a
      diagnostic method and a reference standard listed within the scope of our
      assessment. For comparisons with 3 or more studies, we derived random effects
      estimates of sensitivity, specificity, and prevalence rate. Using the pooled
      estimates, we plotted the performance of each diagnostic test in terms of
      sensitivity and (1 - specificity) and identified the best performer among the
      tests included in the comparison. RESULTS: Among 8 diagnostic methods, pneumatic
      otoscopy had the best apparent performance with a sensitivity of 94% (95%
      confidence interval: 92%-96%) and a specificity of 80% (95% confidence interval:
      75%-86%). However, examiner qualifications were reported inconsistently, and
      training was not specified. CONCLUSIONS: The finding that pneumatic otoscopy can
      do as well as or better than tympanometry and acoustic reflectometry has
      significant practical implications. For the typical clinician, pneumatic otoscopy
      should be easier to use than other diagnostic methods. The important question may
      be what degree of training will be needed for the clinician to be as effective
      with pneumatic otoscopy as were the examiners in the studies reviewed in this
      report.

PMID- 14654614
TI  - Applying the "10 simple rules" of the institute of medicine to management of
      hyperbilirubinemia in newborns.

PMID- 14654615
TI  - Addressing parents' concerns: do vaccines contain harmful preservatives,
      adjuvants, additives, or residuals?
AB  - Vaccines often contain preservatives, adjuvants, additives, or manufacturing
      residuals in addition to pathogen-specific immunogens. Some parents, alerted by
      stories in the news media or information contained on the World Wide Web, are
      concerned that some of the substances contained in vaccines might harm their
      children. We reviewed data on thimerosal, aluminum, gelatin, human serum albumin,
      formaldehyde, antibiotics, egg proteins, and yeast proteins. Both gelatin and egg
      proteins are contained in vaccines in quantities sufficient to induce rare
      instances of severe, immediate-type hypersensitivity reactions. However,
      quantities of mercury, aluminum, formaldehyde, human serum albumin, antibiotics,
      and yeast proteins in vaccines have not been found to be harmful in humans or
      experimental animals.

PMID- 14654617
TI  - Relationship between Wilson-Mikity syndrome and the new bronchopulmonary
      dysplasia.

PMID- 14654618
TI  - Resolving our uncertainty about oxygen therapy.

PMID- 14654619
TI  - Zinc, low birth weight, and breastfeeding.

PMID- 14654620
TI  - The difficulty of diagnosing ventilator-associated pneumonia.

PMID- 14654621
TI  - Bullying: why all the fuss?

PMID- 14654622
TI  - Cost-effectiveness of inhaled nitric oxide in the treatment of neonatal
      respiratory failure in the US.

PMID- 14654623
TI  - Spontaneous regression of severe acquired infantile hypothyroidism associated
      with multiple liver hemangiomas.
AB  - A 9-week-old infant presented with severe postnatal hypothyroidism. His
      hypothyroidism corrected only after his L-thyroxine dose was progressively
      increased to 28 micro g/kg/d. At 6 months of age, multiple clinically
      asymptomatic hepatic hemangiomas were detected and support a diagnosis of
      consumptive hypothyroidism as a result of increased type 3 iodothyronine
      deiodinase activity in the hemangiomas. Coincident with the involution of the
      hemangiomas, the child's hypothyroidism improved and L-thyroxin replacement could
      be stopped at the age of 3 years. Despite some degree of hypothyroidism for
      several weeks during infancy, his growth and development have been normal.

PMID- 14654624
TI  - Streptococcal intertrigo: an underrecognized condition in children.
AB  - Group A beta-hemolytic streptococci have been implicated in a variety of common
      childhood cutaneous infections. Infants and young children may be particularly
      susceptible to a form of streptococcal intertrigo that has heretofore been
      underrecognized in this population. Manifesting as intense, fiery-red erythema
      and maceration in the intertriginous folds of the neck, axillae, or inguinal
      spaces, the condition is characterized by a distinctive foul odor and an absence
      of satellite lesions. Specific clinical features help differentiate this
      condition from its clinical mimics. Topical and oral antibiotic therapy with or
      without concomitant low-potency topical steroid application is generally
      curative.

PMID- 14654625
TI  - Use of intravenous immunoglobulin in children with stevens-johnson syndrome and
      toxic epidermal necrolysis: seven cases and review of the literature.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are the most severe
      cutaneous reactions that occur in children. Off-label use of human intravenous
      immunoglobulin (IVIG) has been reported in a number of autoimmune and cell
      mediated blistering disorders of the skin, including severe cutaneous drug
      reactions. We review 28 previous reports in which IVIG was used in pediatric
      patients with SJS and toxic epidermal necrolysis and discuss our experience in 7
      children with SJS, in whom no new blisters developed within 24 to 48 hours after
      IVIG administration and rapid recovery ensued. IVIG seems to be a useful and safe
      therapy for children with severe cutaneous drug reactions. Well-controlled,
      prospective, multicenter clinical trials are needed to determine optimal dosing
      guidelines and to compare the efficacy and safety of IVIG with other potentially
      effective modalities.

PMID- 14654626
TI  - Families and adoption: the pediatrician's role in supporting communication.
AB  - Each year, more children join families through adoption. Pediatricians have an
      important role in assisting adoptive families in the various challenges they may
      face with respect to adoption. The acceptance of the differences between families
      formed through birth and those formed through adoption is essential in promoting
      positive emotional growth within the family. It is important for pediatricians to
      be informed about adoption and to share this knowledge with adoptive families.
      Parents need ongoing advice with respect to adoption issues and need to be
      supported in their communication with their adopted children.

PMID- 14654627
TI  - Revised indications for the use of palivizumab and respiratory syncytial virus
      immune globulin intravenous for the prevention of respiratory syncytial virus
      infections.
AB  - Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous (RSV
      IGIV) are licensed by the Food and Drug Administration for use in preventing
      severe lower respiratory tract infections caused by respiratory syncytial virus
      (RSV) in high-risk infants, children younger than 24 months with chronic lung
      disease (formerly called bronchopulmonary dysplasia), and certain preterm
      infants. This statement provides revised recommendations for administering RSV
      prophylaxis to infants and children with congenital heart disease, for
      identifying infants with a history of preterm birth and chronic lung disease who
      are most likely to benefit from immunoprophylaxis, and for reducing the risk of
      RSV exposure and infection in high-risk children. On the basis of results of a
      recently completed clinical trial, prophylaxis with palivizumab is appropriate
      for infants and young children with hemodynamically significant congenital heart
      disease. RSV-IGIV should not be used in children with hemodynamically significant
      heart disease. Palivizumab is preferred for most high-risk infants and children
      because of ease of intramuscular administration. Monthly administration of
      palivizumab during the RSV season results in a 45% to 55% decrease in the rate of
      hospitalization attributable to RSV. Because of the large number of infants born
      after 32 to 35 weeks' gestation and because of the high cost, immunoprophylaxis
      should be considered for this category of preterm infants only if 2 or more risk
      factors are present. High-risk infants should not attend child care during the
      RSV season when feasible, and exposure to tobacco smoke should be eliminated.

PMID- 14654628
TI  - Revised indications for the use of palivizumab and respiratory syncytial virus
      immune globulin intravenous for the prevention of respiratory syncytial virus
      infections.
AB  - Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous (RSV
      IGIV) are licensed by the Food and Drug Administration for use in preventing
      severe respiratory syncytial virus (RSV) infections in high-risk infants,
      children younger than 24 months with chronic lung disease (formerly called
      bronchopulmonary dysplasia), and certain preterm infants. This report summarizes
      the clinical trial information on which the guidance in the accompanying policy
      statement for administering RSV prophylaxis to certain children with a history of
      preterm birth, chronic lung disease, or congenital heart disease is based. On the
      basis of results of a recently completed clinical trial, palivizumab is
      appropriate for infants and young children with hemodynamically significant
      congenital heart disease. RSV-IGIV should not be used in children with
      hemodynamically significant heart disease. Palivizumab is preferred for most high
      risk infants and children because of ease of intramuscular administration.
      Monthly administration of palivizumab during the RSV season results in a 45% to
      55% decrease in the rate of hospitalization attributable to RSV. Because of the
      large number of infants born after 32 to 35 weeks' gestation and because of the
      high cost, immunoprophylaxis should be considered for this category of preterm
      infants only if 2 or more risk factors are present.

PMID- 14654629
TI  - Familial hyperbilirubinemia in ABO-incompatible neonates.

PMID- 14654630
TI  - Survivors of childhood cancer: using siblings as a control group.

PMID- 14654631
TI  - Pain relievers and asthma.

PMID- 14654632
TI  - Formula supplementation and growth.

PMID- 14654633
TI  - Crotaline Fab antivenom for treatment of children with rattlesnake envenomation.

PMID- 14654634
TI  - Attention-deficit/hyperactivity disorder treatment and later drug use.

PMID- 14654635
TI  - Continuous propofol infusion in 142 critically ill children.

PMID- 14654636
TI  - Imaging before appendectomy.

PMID- 14654637
TI  - Childhood motor disorders.

PMID- 14654638
TI  - Sleep need in children.

PMID- 14654639
TI  - Pulse oximetry in bronchiolitis patients.

PMID- 14654640
TI  - Inhaled corticosteroids and urinary free cortisol.

PMID- 14654641
TI  - Obstacles to the elimination of Haemophilus influenzae type b disease: three
      illustrative cases.

PMID- 14654642
TI  - National estimates of health services expenditures for children with behavioral
      disorders: an analysis of the medical expenditure panel survey.
AB  - BACKGROUND: Children with attention-deficit/hyperactivity disorder and asthma
      incur similar health care costs that are greater than those of most children
      without these conditions. Preliminary findings suggest that children with
      emotional behavioral disorders, anxiety and depression, incur even greater costs.
      OBJECTIVE: To determine if children with behavioral disorders have similar health
      services expenditures as children with physical conditions and to assess whether
      children with emotional behavioral disorders incur greater expenditures than
      children with disruptive behavioral disorders. METHODS: Children 2 to 18 years
      old who were members of households participating in the 1996 Medical Expenditure
      Panel Survey were eligible for this retrospective cohort study. Children with
      common behavioral disorders selected a priori were identified by using truncated
      International Classification of Diseases (Ninth Revision) codes obtained from
      household interviews. Children with common physical conditions (asthma, epilepsy,
      and diabetes) and children without these conditions served as controls. Estimates
      were weighted to reflect the complex sampling scheme. Expenditures for health
      services were compared. RESULTS: Of 3955 eligible children weighted to represent
      >44 million, 7.1% were identified with a behavioral disorder: 4.5% with
      disruptive disorders; 2.1% with emotional disorders; and 0.5% with miscellaneous
      disorders. Children with behavioral disorders incurred overall expenditures
      similar to children with physical conditions (adjusted 1492 dollars vs 1245
      dollars; P =.18) but greater than children without these conditions (adjusted
      1492 dollars vs 834 dollars; P =.001). Children with behavioral disorders had
      greater expenditures for office-based visits (adjusted 410 dollars; 95%
      confidence interval: 146-672 dollars) and prescription medications (adjusted 361
      dollars; 95% confidence interval: 72-648 dollars) than those of children in
      either control group. Among children with behavioral disorders, children with
      emotional disorders incurred substantially greater overall expenditures (adjusted
      2152 dollars vs 1026 dollars; P =.003) than children with disruptive disorders.
      Children with emotional disorders incurred greater hospitalization expenditures
      (664 dollars vs 43 dollars; P =.01) but lower pharmacy expenditures (154 dollars
      vs 307 dollars; P =.001) than children with disruptive disorders. CONCLUSIONS: In
      this nationally representative sample, children with behavioral disorders
      incurred overall health care costs similar to children with physical conditions
      but greater than children without any of these conditions because of increased
      costs for office-based visits and prescription medications. However, costs were
      not uniform among children with behavioral disorders. Children with emotional
      disorders incurred twofold higher costs than children with disruptive disorders.
      Greater recognition of children with emotional disorders and efforts to address
      the high rate of hospitalizations in this population are warranted.

PMID- 14654643
TI  - A school-based exercise intervention elicits substantial bone health benefits: a
      2-year randomized controlled trial in girls.
AB  - OBJECTIVE: Childhood weight-bearing physical activity is recognized as an
      important determinant of peak bone mass, and physical activity intervention may
      represent a feasible strategy for primary prevention of osteoporosis. Previous
      school-based exercise interventions have all been of <10 months in duration. We
      implemented a high-impact, circuit-based, jumping intervention (10 minutes, 3
      times a week) over 2 school years and compared changes in bone mineral content
      (BMC) over 20 months (2 school years) in 9.9 +/- 0.6-year-old intervention girls
      (N = 32) and controls (10.3 +/- 0.4 years, N = 43). METHODS: We measured BMC for
      the total body, lumbar spine, proximal femur (and femoral neck and trochanteric
      subregions), and lean and fat mass by dual-energy radiograph absorptiometry
      (Hologic QDR 4500), and height, sitting height, leg length, and weight at
      baseline and 20 months. We assessed Tanner stage, general physical activity, and
      calcium intake by questionnaire. RESULTS: Girls were Tanner breast stage 1 to 3
      at baseline. There were no significant differences in baseline or 20-month change
      in body size or composition, average physical activity, or calcium intake between
      groups. There were substantially greater gains in lumbar spine (41.7% vs 38.0%)
      and femoral neck (24.8% vs 20.2%) BMC in intervention than in control girls (P
      <.05, analysis of covariance; covariates were baseline BMC and height, change in
      height, physical activity, and final Tanner stage). CONCLUSION: Three brief
      sessions of high-impact exercise per week implemented over 2 consecutive years
      within the elementary school curriculum elicited a substantial bone mineral
      accrual advantage in pubertal girls.

PMID- 14654644
TI  - Injection-site reactions to booster doses of acellular pertussis vaccine: rate,
      severity, and anticipated impact.
AB  - BACKGROUND: Acellular pertussis (aP)-containing vaccines cause fewer adverse
      events than whole-cell versions for primary doses. Booster doses, however, may be
      followed by extensive injection-site reactions. This study compares the
      frequency, severity, and impact of local reactions among children receiving 5
      consecutive doses of an aP combination vaccine (including inactivated polio
      virus, conjugated Haemophilus influenzae type b antigen, and diphtheria and
      tetanus toxoids) to children receiving a mixed series of whole-cell and aP
      combination vaccines. METHODS: Participants were parents or guardians of children
      4 to 6 years old immunized at public health clinics across British Columbia,
      Canada. This included 398 children receiving the fifth consecutive dose of an aP
      combination vaccine and 402 receiving the fifth dose in a mixed series consisting
      of at least 1 prior dose of whole-cell pertussis combination vaccine with the
      remainder as aP combination vaccine. A cross-sectional telephone survey evaluated
      the extent of local reactions 48 to 96 hours after immunization by asking
      participants to compare the size of redness and swelling with familiar household
      items such as Oreo cookies or coins. Associated discomfort and impact on
      recreational activities, health care utilization, parental time off work, and
      attitudes toward immunization were also assessed. RESULTS: Children who received
      the fifth consecutive dose of an aP combination vaccine more often experienced
      redness (24%) or swelling (16%) the size of an Oreo cookie or larger (>or=46 mm)
      than children given a mixed series (10% and 9%, respectively) but less often
      experienced tenderness or limitation of movement at the injection site. Related
      health care utilization was low. There was no discernible effect on participation
      in recreational activities or parental attitudes toward vaccine; 90% would
      recommend the same vaccine to others with children of the same age. CONCLUSIONS:
      We conclude that injection-site reactions are more extensive after the fifth
      consecutive dose of an aP combination vaccine compared with the fifth dose in a
      mixed series of whole-cell and aP combination vaccines. These reactions are
      unlikely to affect parental acceptance of immunization recommendations or health
      care utilization.

PMID- 14654645
TI  - Childhood obesity: a risk factor for omental torsion.
AB  - PURPOSE: To determine the risk factors and clinical presentation of primary
      omental torsion (POT) in children. METHODS: Histopathology records of a pediatric
      hospital from January 1993 to March 2003 were reviewed to identify cases of POT.
      Hospital charts of patients diagnosed with POT were reviewed for demographic data
      and clinical presentation. RESULTS: A diagnosis of POT was recorded in 12 of
      41,987 pathology records reviewed. Most of the patients were white (92%), male
      (75%), and 9 to 16 years old (75%). Weight percentiles were >or=95th in 11 (92%)
      of 12 patients. Body mass index was calculated in 9 of the 12 cases with 8 >95th
      percentile. Clinical presentation including right-sided abdominal pain,
      tenderness, and anorexia closely mimics acute appendicitis. CONCLUSIONS: Obesity
      seems to be an important risk factor for POT in children. The presentation for
      POT seems to be less acute than with other causes of surgical abdomen.

PMID- 14654646
TI  - Evaluation of failure to thrive: diagnostic yield of testing for renal tubular
      acidosis.
AB  - BACKGROUND: Failure to thrive (FTT) poses a diagnostic dilemma for pediatricians.
      The kidney disorder that is considered most often is renal tubular acidosis
      (RTA). However, the prevalence of RTA may be overestimated, leading to
      unnecessary referrals for subspecialty evaluation. Moreover, preliminary data
      suggest that venous blood gas (VBG) testing may provide a more accurate
      measurement of the serum bicarbonate concentration than routine biochemical
      testing. OBJECTIVE: 1) To compare the results of bicarbonate measurements by
      using VBG and routine clinical biochemistry methods under a variety of in vitro
      conditions; 2) to determine the frequency of RTA as a cause of FTT; and 3) to
      assess the utility of VBG measurement of serum bicarbonate in the clinical
      assessment of RTA. EXPERIMENTAL DESIGN AND METHODS: In blood samples collected
      from healthy volunteers, bicarbonate was measured by using a VBG apparatus and a
      clinical biochemistry analyzer under a variety of in vitro conditions including
      variation in time until sample processing (0-4 hours), variations in temperature
      (room temperature versus on ice), addition of sodium fluoride, or addition of
      heparin. A retrospective chart review was also performed of all children referred
      to the renal clinic for evaluation of FTT during the 5-year period of 1997 to
      2002. The following data were collected for each case: demographic and clinical
      information and laboratory testing including serum bicarbonate determined by both
      routine biochemical testing and VBG analysis. Data are reported as mean +/-
      standard deviation. RESULTS: In the in vitro studies, VBG determination of
      bicarbonate concentration consistently yielded a value that was 3 to 6 mmol/L
      higher than routine biochemical analysis regardless of whether the sample was
      processed immediately or up to 4 hours later, maintained at room temperature or
      on ice until the measurement was performed, or the sample tube contained sodium
      fluoride or heparin. Thirty-six children were referred to exclude a renal
      etiology of FTT with a presumptive diagnosis of RTA in all cases. The patient
      group was comprised of 16 males and 20 females whose ages ranged from 4 to 156
      months (mean: 27 +/- 33 months). The serum bicarbonate concentration determined
      by biochemical testing was 18 +/- 4 mmol/L, whereas the bicarbonate level by VBG
      was 24 +/- 3 mmol/L. The mean difference between the bicarbonate by VBG and
      bicarbonate by routine biochemistry measurements was 5.6 +/- 4.4. Only 1 child
      (2.8%) was confirmed to have RTA. CONCLUSIONS: RTA is a rare renal cause of FTT
      in children. VBG determination of serum bicarbonate yielded a significantly
      higher value than the result obtained by routine biochemical testing under both
      in vitro and in vivo conditions. These data suggest that reliance on routine
      biochemical testing results in an overestimation of the importance of RTA as a
      cause of FTT. We recommend the use of a VBG determination of serum bicarbonate
      concentration for the evaluation of a child with FTT who is thought to have a
      metabolic acidosis. Adoption of this practice will reduce the number of children
      suspected of having RTA and decrease the need for referral to a nephrologist for
      further evaluation.

PMID- 14654647
TI  - Value and limitations of the von Reyn, Duke, and modified Duke criteria for the
      diagnosis of infective endocarditis in children.
AB  - OBJECTIVE: To compare the sensitivity of 3 different criteria-von Reyn, Duke, and
      modified Duke-in diagnosing infective endocarditis (IE) in children. STUDY
      DESIGN: Retrospective case study in a tertiary pediatric hospital. METHODS AND
      RESULTS: Between 1985 and 2001, 41 episodes of IE were documented in 40 children
      (median: 7 years old; range: 1 week to 18 years). The diagnosis was based on
      echocardiographic and microbiologic or pathologic findings. The initial
      echocardiogram suggested IE in 95% of the cases. Main findings were vegetations
      in 36, perivalvular abscess in 4, and/or new valvular leaks in 6 cases. In 31
      (76%) of the 41 episodes, the causative organisms were identified directly by
      specimen bacteriology or blood cultures (BCs) or indirectly by polymerase chain
      reaction or serology. Sensitivities of the von Reyn, Duke, and modified Duke
      criteria in diagnosing IE were 63%, 81%, and 88%, respectively. In 10 cases
      (22%), the diagnosis of IE was "rejected" by the von Reyn criteria but was
      "definite or possible" by the Duke and modified Duke criteria. In 3 cases, the
      diagnosis of IE was "possible" by the Duke but "definite" by the modified Duke
      criteria: 2 of the 3 cases had 1 major and >or=3 minor symptoms, and 1 had Q
      fever. Five episodes (12%) were classified as "possible" IE by the modified Duke
      criteria: although major findings were present on echocardiography, no organism
      was identified on repeat BCs. Positive BC was the only criterion that
      differentiated "definite" from "possible" IE. CONCLUSIONS: The modified Duke
      classification was more sensitive in diagnosing IE in children than the von Reyn
      and Duke criteria. Still, 12% failed to be classified as "definite" IE by the
      modified Duke criteria. This illustrates the importance of positive BCs as a
      major IE criterion while significant echocardiographic findings are less
      considered by the presently used criteria.

PMID- 14654648
TI  - Chromosome 22q11 deletion in patients with ventricular septal defect: frequency
      and associated cardiovascular anomalies.
AB  - BACKGROUND: A ventricular septal defect (VSD) is the most common form of
      congenital heart disease and is one of the most common cardiovascular anomalies
      in individuals with chromosome 22q11 deletion syndrome. However, the frequency of
      a chromosome 22q11 deletion in patients with a VSD is not known. In addition,
      among patients with a VSD, it is not clear whether particular types of VSD or
      associated cardiovascular phenotypic features are associated with a chromosome
      22q11 deletion. METHODS: We prospectively enrolled 125 patients with a
      conoventricular (n = 100), posterior malalignment (n = 14), or conoseptal
      hypoplasia (n = 11) VSD who were admitted to Children's Hospital of Philadelphia
      between November 1991 and December 2001. Patients were studied for a chromosome
      22q11 deletion by using fluorescence in situ hybridization. RESULTS: A chromosome
      22q11 deletion was detected in 12 (10%) of the 125 patients. Anatomic features
      that were significantly associated with a chromosome 22q11 deletion included
      abnormal aortic arch sidedness, an abnormal aortic arch branching pattern, a
      cervical aortic arch, and discontinuous pulmonary arteries. There was no
      correlation between the type of VSD and chromosome 22q11 deletion. Of 20 patients
      with an abnormal aortic arch and/or discontinuous pulmonary arteries, 45% had a
      chromosome 22q11 deletion compared with only 3% of those with a left aortic arch,
      normal aortic arch branching pattern, and continuous branch pulmonary arteries
      CONCLUSIONS: A chromosome 22q11 deletion is common in individuals with a
      conoventricular, posterior malalignment, or conoseptal hypoplasia VSD and
      anomalies of the aortic arch or branch pulmonary arteries. On the basis of these
      findings, at a minimum, we recommend testing for a chromosome 22q11 deletion in
      patients with these types of VSD who have abnormalities of aortic arch sidedness
      or branching, a cervical aortic arch, and/or discontinuous pulmonary arteries.
      Testing of patients with these types of VSD but a normal aortic arch and
      pulmonary arteries may be performed routinely or guided by the presence of
      associated noncardiovascular features of chromosome 22q11 deletion syndrome.

PMID- 14654649
TI  - Lyme disease presenting with persistent headache.
AB  - Increased intracranial pressure in patients with Lyme disease is an uncommon but
      reported finding. We discuss 2 patients from Lyme endemic areas who initially
      presented with headache, nausea, and vomiting and were eventually found to have
      increased intracranial pressure, a mild cerebrospinal fluid pleocytosis, and
      positive Lyme titers. It has been shown that increased intracranial pressure in
      association with neuroborreliosis can lead to blindness. In endemic areas, it is
      important for practitioners to consider Lyme disease when patients present with
      persistent headache, especially in those who have evidence of increased
      intracranial pressure.

PMID- 14654650
TI  - Neurosarcoid presents differently in children than in adults.
AB  - BACKGROUND: Neurosarcoid is seldom recognized in children. In the absence of any
      large pediatric series, it has been assumed that the presenting signs and
      symptoms are identical in adults and children. OBJECTIVE: To test the hypothesis
      that childhood neurosarcoid differs in presenting signs and symptoms from
      neurosarcoid in adults. METHODS: We tabulated the initial neurologic signs and
      symptoms in all reported cases of childhood sarcoid with evidence of central
      nervous system involvement. These data then were compared with published studies
      of adult neurosarcoid. RESULTS: Twenty-nine cases (from the English, French, and
      German literature) had descriptions of presenting signs and symptoms. Ages were 3
      months to 18 years; 48% (14 of 29) presented before 13 years. Seizures were the
      most common presenting symptom (38%, 11 of 29), and 73% of these children (8 of
      11) were <13 years old at presentation. Twenty-one percent (6 of 29) had cranial
      nerve involvement at presentation, and all were >or=12 years old. Twenty-one
      percent (6 of 29) had hypothalamic dysfunction. Five children presented with
      headache, 4 with motor signs, and 3 with papilledema. Twenty-four percent (7 of
      29) had mass lesions on imaging. CONCLUSIONS: Children with neurosarcoid present
      differently than do adults. Children are more likely to have seizures, less
      likely to have cranial nerve palsies, and perhaps more likely to have a space
      occupying lesion. Our analysis of the cases available for review in the published
      literature suggests that children evolve to an adult pattern as they progress
      through adolescence.

PMID- 14654651
TI  - Diaphragmatic hernia simulating a left pleural effusion.
AB  - We review a case of a diaphragmatic hernia simulating on chest radiograph left
      lower lobe pneumonia and associated pleural effusion. We also characterize the
      atypical chest radiographic findings of this patient and recommend further
      imaging with computed tomography in unusual patient presentations.

PMID- 14654652
TI  - Henoch-Schonlein purpura following a meningococcal vaccine.
AB  - We report a 17-year-old girl who developed Henoch-Schonlein purpura 10 days after
      receiving a meningococcal vaccine (Menomune). To our knowledge, this is the first
      case report of Henoch-Schonlein purpura temporally associated with the
      tetravalent serogroups A, C, W-135, and Y meningococcal vaccine administered in
      the United States.

PMID- 14654653
TI  - Are children with Kawasaki disease and prolonged fever at risk for macrophage
      activation syndrome?
AB  - Kawasaki disease (KD) patients are known to be at increased risk for coronary
      artery lesions. We present evidence of another possible complication associated
      with KD: macrophage activation syndrome (MAS). In this case, a patient with KD
      and prolonged fever developed MAS. This case is of particular interest because of
      the late age of onset and recurrent nature of KD as well as the complication of
      MAS. We also present a review of the literature that supports the inclusion of
      MAS as an infrequent complication of KD.

PMID- 14654655
TI  - The National Institute of Child Health and Human Development and phenylketonuria.
AB  - The National Institute of Child Health and Human Development (NICHD) was
      established shortly after the Guthrie test for screening newborn infants for
      phenylketonuria (PKU) was introduced. The NICHD supported the study demonstrating
      the long-term efficacy of screening and a low-phenylalanine diet in preventing
      mental retardation. With the identification of the adverse impact on fetal
      development of high intrauterine phenylalanine exposure from a mother with PKU,
      the NICHD organized and supported the study reported here, demonstrating the
      protective effect of phenylalanine restriction of the mother's diet during
      pregnancy. The study provides clear guidance for the management of pregnancy in
      women with PKU.

PMID- 14654656
TI  - Historical background for the maternal PKU syndrome.
AB  - OBJECTIVE: To provide information on the history of maternal phenylketonuria.
      METHODS: A review of the literature and personal observations were conducted.
      RESULTS: Compilation of sequential information about the development of our
      understanding of maternal PKU was produced. CONCLUSIONS: The history of maternal
      PKU reflects continuous additions to our understanding of this teratogenic
      syndrome.

PMID- 14654657
TI  - Research design, organization, and sample characteristics of the Maternal PKU
      Collaborative Study.
AB  - OBJECTIVE: The Maternal PKU Collaborative Study (MPKUCS) was initiated in 1984 by
      the National Institute of Child Health and Human Development (NICHD). The purpose
      was to assess the efficacy of dietary restriction of phenylalanine in reducing
      morbidity in offspring of women with hyperphenylalaninemia (HPA). A contract was
      awarded to Childrens Hospital Los Angeles as the Coordinating Center to provide
      implementation of the research protocol, data collection, and analysis. METHODS:
      The Study included four regional contributing centers: Childrens Hospital Los
      Angeles (Western Region), Boston Children's Hospital (Northeast Region),
      University of Illinois (Midwest Region), and University of Texas Medical Branch,
      Galveston (Southeast Region). Within each region, many participating clinics were
      responsible for obstetric care, treatment, and monitoring protocols. In 1985,
      Canada joined the MPKUCS, and in 1992, Germany entered. They were selected
      because they provided dietary supplies and strong professional services.
      Acquisition began in 1984 and ended in October 1995. The study included 574
      pregnancies in women with HPA and 100 control subjects matched on age, race,
      parity, and weeks of gestation. The sample included women with blood
      phenylalanine values >240 micromol/L, 66% of whom had classical PKU, 22% had
      atypical PKU, and 12% had mild HPA. Informed consents were obtained on all
      participants. The women ranged in age from 15 to 36 years of age, with a mean age
      at conception of 23 years. Teenage pregnancies accounted for 19%. Seventy-five
      percent graduated from high school. Offspring included 416 newborns, 317 of whom
      were evaluated at 4 years of age and 289 at 6 to 7 years. Follow-up involved
      medical, nutritional, psychosocial, and psychological assessments. CONCLUSION:
      Women with PKU treated before conception and in control of their blood
      phenylalanine levels between 120 and 360 micromol/L (2-6 mg) exhibited normal
      pregnancies and neonatal outcome. Surprisingly, women who achieved control in the
      recommended range by 8 weeks of pregnancy also had a normal fetal outcome.

PMID- 14654658
TI  - The Maternal Phenylketonuria International Study: 1984-2002.
AB  - OBJECTIVE: The purpose of this report is to review the obstetric medical,
      psychological, and nutritional aspects and outcome of the women and offspring
      enrolled in the Maternal Phenylketonuria Study, which was established to assess
      the efficacy of a phenylalanine (Phe)-restricted diet in preventing the morbidity
      associated with this disorder. METHODS: A total of 382 women with
      hyperphenylalaninemia (HPA) were enrolled in the study and completed 572
      pregnancies. Outcome measures were analyzed with chi2, Fisher exact text,
      analysis of variance, t test, Wilcoxon nonparametric test, and multiple logistic
      regression. Outcome measures were stratified according to maternal HPA
      classification and the time when dietary control was achieved. RESULTS: Optimal
      birth outcomes occurred when maternal blood Phe levels between 120 and 360
      micromol/L were achieved by 8 to 10 weeks of gestation and maintained throughout
      pregnancy (trimester averages of 600 micromol/L). Mothers with mild HPA achieved
      similar birth outcomes as mothers who were in control preconceptually and those
      in control by 8 to 10 weeks of pregnancy. CONCLUSIONS: Before conception,
      counseling and early entrance into a prenatal care program is essential in
      achieving optimal fetal outcome in women with HPA. The achievement of pre- and
      periconceptional dietary control with a Phe-restricted diet significantly
      decreased morbidity in the offspring of women with HPA.

PMID- 14654659
TI  - Impact of the phenylalanine hydroxylase gene on maternal phenylketonuria outcome.
AB  - OBJECTIVE: The aim of the present study was to examine to what extent maternal
      and offspring phenylalanine hydroxylase (PAH) genotypes in conjunction with
      maternal IQ and dietary control during pregnancy are related to cognitive
      development in offspring of women with phenylketonuria (PKU). METHODS: PAH gene
      mutations were determined in 196 maternal PKU subjects and their offspring. The
      women were grouped according to PAH genotype, which predicts the metabolic
      phenotype (severe PKU, mild PKU, and mild hyperphenylalaninemia [MHP]). IQ was
      determined in both the mothers (Wechsler Adult Intelligence Scale-Revised at >18
      years) and their children (Wechsler Intelligence Scale for Children-Revised at >
      or = 6-7 years of age). RESULTS: According to PAH genotypes, 62% of the women
      exhibited severe PKU, 19% exhibited mild PKU, and 19% exhibited MHP. Maternal IQ
      increased, and the assigned phenylalanine (Phe) levels decreased with decreasing
      severity of PAH genotype. In offspring of mild maternal PKU, multiple regression
      analysis showed offspring IQ to be significantly related to maternal IQ but not
      to Phe exposure during pregnancy, which was <750 micromol/L in all cases of mild
      PKU. In offspring of mothers with severe PKU and average Phe exposure during
      pregnancy of 360 to 750 micromol/L, multiple regression analysis revealed both
      maternal IQ and Phe exposure to be significant predictors of offspring IQ. When
      average Phe exposure was <360 micromol/L, cognitive development was normal (mean
      IQ: 105), whereas an average Phe exposure of >750 micromol/L severely depressed
      offspring IQ (mean IQ: 56) in this group regardless of maternal IQ. It could not
      be documented that the offspring PAH genotype affects cognitive development.
      CONCLUSION: Female individuals with severe PKU should be offered a diet for a
      lifetime. If good metabolic control is established, then women with PKU will have
      children with IQ scores that are not influenced by their disease.

PMID- 14654660
TI  - Role of nutrition in pregnancy with phenylketonuria and birth defects.
AB  - OBJECTIVE: The maternal phenylketonuria (PKU) syndrome is caused by high blood
      phenylalanine (Phe) levels during pregnancy, leading to a host of birth defects,
      especially microcephaly and congenital heart disease (CHD). For finding whether
      the maternal PKU syndrome could be prevented, an international collaborative
      study was organized to evaluate treatment with a Phe-restricted diet. Blood Phe
      levels, maternal weight gain, and nutrient intakes during pregnancy were
      evaluated as to their effect on the rate of microcephaly and CHD in the
      offspring. METHODS: The study was a prospective, longitudinal effort aimed at
      lowering blood Phe during pregnancy. Women were enrolled at time of referral for
      pregnancy. Nutrient intake analysis, which serves as the basis for this report,
      was available from 251 pregnancies. Subjects were stratified by blood Phe control
      of < or =600 micromol/L by 8 weeks gestation or >600 micromol/L by 8 weeks
      gestation. Outcome of these pregnancies was correlated to blood Phe levels,
      weight gain, and nutrient intake. RESULTS: The study goal was to attain blood Phe
      levels of 120 to 360 micromol/L 3 months preconception; however, this goal was
      achieved by only a limited number of patients. Therefore, the data presented were
      based on blood Phe control < or =600 micromol/L or >600 micromol/L by 8 weeks of
      gestation. Blood Phe control of < or =600 micromol/L by 8 weeks of gestation was
      attained by 86 (34.3%) of the 251 women in this study, whereas the other 165
      women had blood Phe control >600 micromol/L by 8 weeks of gestation. Of the 251
      offspring, 166 were born with normal head circumference and 85 were born with
      microcephaly (<2 standard deviations below normal). Women with blood Phe >600
      micromol/L at 8 weeks of gestation included 78 (92%) of the 85 infants with
      microcephaly compared with 8% in the group of women who had blood Phe levels < or
      =600 micromol/L. Weight gain during pregnancy was related to the rate of
      microcephaly. The highest occurrence of microcephaly (58%) was found in the
      pregnant women who gained <70% of recommended weight gain. Stepwise logistic
      regression analysis was used to determine factors associated with microcephaly.
      Significant factors included higher blood Phe levels when off diet, higher
      average Phe exposure during the pregnancy, low prepregnancy weight, poor weight
      gain during the pregnancy, and lower intake of protein and higher iron intake
      during the pregnancy. Infants with CHD were found only in the group of women who
      had blood Phe levels >600 micromol/L by 8 weeks of gestation. There was a higher
      rate of CHD in the offspring who were born to women who consumed <50% of the
      recommended intake of protein in the first trimester. The main source of protein
      for women with PKU is the medical food; therefore, when protein intake was low,
      vitamin and mineral intakes were also inadequate. CONCLUSIONS: The data indicate
      that blood Phe control and how soon it is attained during pregnancy with PKU is
      important. Normal pregnancy weight gain should be encouraged to reduce
      microcephaly. Adequate protein and vitamin intakes early in pregnancy may have a
      protective effect for the prevention of CHD, even if blood Phe is elevated. The
      rate of microcephaly and CHD may be reduced if nutrient intake is optimal while
      attempting to control blood Phe levels.

PMID- 14654661
TI  - Relation of prenatal phenylalanine exposure to infant and childhood cognitive
      outcomes: results from the International Maternal PKU Collaborative Study.
AB  - OBJECTIVE: The primary aims of this study were to model the form of the relation
      between prenatal exposure to phenylalanine (Phe) and measures of offspring
      intellectual development and to estimate the developmental relations of maternal
      demographic, pregnancy-related, and perinatal variables on offspring intelligence
      during infancy and childhood. METHODS: The participants were the 413 children and
      their mothers from the International Maternal PKU Collaborative Study. RESULTS:
      Results supported a nonlinear relation between prenatal Phe exposure and
      offspring cognitive outcomes, with damage to the developing fetus if average Phe
      levels are above approximately 360 micromol/L. Moreover, prenatal Phe exposure
      had a strong effect on offspring outcomes at 1 year of age and was the only one
      of the background, pregnancy-related, or perinatal variables to influence
      directly offspring outcomes at 2, 4, and 7 years of age. CONCLUSION: The present
      study was able to document the importance of prenatal exposure to Phe for
      predicting offspring cognitive outcomes in the presence of other predictors of
      these outcomes.

PMID- 14654662
TI  - Cognitive and behavioral development in maternal phenylketonuria offspring.
AB  - OBJECTIVE: To assess cognitive and behavioral outcome in treated maternal
      phenylketonuria (PKU) offspring. METHODS: In this prospective, longitudinal
      study, 228 children who were born to mothers with treated PKU or untreated mild
      hyperphenylalaninemia were compared with 70 control subjects at 7 years of age.
      RESULTS: Offspring cognitive outcome negatively correlated with the number of
      gestational weeks that elapsed until maternal metabolic control was achieved (r =
      -0.61). Behavioral outcome was similarly affected. Postnatal measurement of
      stimulation in the home was also related to offspring IQ. CONCLUSIONS: Children
      who are born to mothers who have PKU and attain metabolic control before or very
      early in pregnancy seem to begin life with undiminished potential. Delay in
      attainment of maternal metabolic control is associated with declines in offspring
      developmental outcome. The postnatal environment also significantly affects
      outcome. Interventions to improve dietary compliance before and throughout
      pregnancy as well as interventions to improve the postnatal home environment may
      reduce the risks associated with maternal PKU.

PMID- 14654663
TI  - Pregnancy experiences in the woman with mild hyperphenylalaninemia.
AB  - OBJECTIVE: A major issue in maternal phenylketonuria (MPKU) has been whether
      maternal non-PKU mild hyperphenylalaninemia (MHP) is teratogenic. Such untreated
      pregnancies and their outcomes are presented on this report. METHODS: Enrolled
      pregnancies in which the untreated prepregnancy assigned phenylalanine level
      (APL) was no more than 600 micro mol/L were included in the Maternal PKU
      Collaborative Study and were followed according to protocol. RESULTS: Forty-eight
      enrolled women with non-PKU MHP had mean APL 408 +/- 114 micromol/L. They had a
      total of 58 pregnancies that resulted in live births. Fifty were untreated.
      Maternal phenylalanine (Phe) levels in the untreated pregnancies decreased during
      pregnancy for average Phe exposure of 270 +/- 84 micromol/L, virtually identical
      to the level of 269 +/- 136 micromol/L in the 8 treated pregnancies. Birth
      measurements in the 50 offspring from untreated pregnancies were within normal
      limits with z scores of -0.25 for weight, 0.28 for length, and -0.63 for head
      circumference, although birth head circumference was negatively correlated with
      maternal APL (r = -0.30). Only 1 offspring had congenital heart disease.
      Offspring IQ was 102 +/- 15 compared with 96 +/- 14 in the mothers with untreated
      pregnancies and with 109 +/- 21 in control offspring. CONCLUSION: Maternal non
      PKU MHP no more than 600 micromol/L does not require dietary therapy. The
      naturally lower Phe level during pregnancy seems to protect against
      teratogenesis.

PMID- 14654664
TI  - Maternal phenylketonuria: experiences from the United Kingdom.
AB  - Charles Dent was one of the first physicians to recognize the teratogenic effects
      of maternal phenylalanine (Phe) on the fetus in 1956. This article describes the
      clinical experiences of women with phenylketonuria (PKU) within the unit that was
      established by Dent in the United Kingdom. Between 1977 and 2002, 79 infants were
      born to women with PKU. Of the 79, 18 (23%) were conceived while the women were
      on a normal diet with high blood Phe levels. The mean birth weight was 2.89 kg,
      and head circumference was 32.8 cm. At 1 year, the mean developmental quotient
      was 105.5 and at 4 years was 82.3. Four of these infants had congenital heart
      disease (2 of whom died as a result). In the remaining 61 infants, Phe-restricted
      diet started before conception. None of them had congenital heart disease. The
      mean birth weight was 3.23 kg, and head circumference was 34.0 cm. At 1 year,
      mean developmental quotient was 108.0 and at 4 years was 90.9. They continue to
      be followed up with additional neuropsychometric assessments at 8 and 14 years of
      age. This cohort is a proportion of infants who were born to mothers with PKU in
      the United Kingdom. Between 1978 and 1997, 255 live births were reported. Of
      these, 56% were conceived on unrestricted diet with subsequently poor outcome.
      This relatively high rate of conception off PKU diet is likely to reflect the
      scarcity of medical services for adults with metabolic disorders. We conclude
      that many features of the maternal PKU syndrome can be prevented but still occur
      because of the lack of appropriate resources to care for at-risk women. The
      precise targets for blood Phe and other nutrients during pregnancy are not
      entirely clear, neither are the reasons that some offspring are spared the
      harmful effects of Phe. The impact of the postnatal environment in which these
      infants find themselves requires additional assessment, too.

PMID- 14654665
TI  - Structural studies on phenylalanine hydroxylase and implications toward
      understanding and treating phenylketonuria.
AB  - Mutations in the gene encoding for phenylalanine hydroxylase (PAH) result in
      phenylketonuria (PKU) or hyperphenylalaninemia (HPA). Several 3-dimensional
      structures of truncated forms of PAH have been determined in our laboratory and
      by others, using x-ray crystallographic techniques. These structures have allowed
      for a detailed mapping of the >250 missense mutations known to cause PKU or HPA
      found throughout the 3 domains of PAH. This structural information has helped
      formulate rules that might aid in predicting the likely effects of unclassified
      or newly discovered PAH mutations. Also, with the aid of recent crystal structure
      determinations of co-factor and substrate analogs bound at the PAH active site,
      the recently discovered tetrahydrobiopterin-responsive PKU/HPA genotypes can be
      mapped onto the PAH structure, providing a molecular basis for this
      tetrahydrobiopterin response.

PMID- 14654666
TI  - Potential role of tetrahydrobiopterin in the treatment of maternal
      phenylketonuria.
AB  - OBJECTIVE: To evaluate the clinical relevance of tetrahydrobiopterin (BH4)
      supplementation for pregnant women with phenylketonuria
      (PKU)/hyperphenylalaninemia (HPA) and the possibility of treating these patients
      with BH4 instead of a phenylalanine (Phe)-restricted diet. METHODS: Genotyping
      was performed on 41 patients with PKU/HPA identified by newborn screening.
      Evaluating the genotype according to their BH4 responsiveness is published.
      Follow-up of 3 patients with mild PKU treated with BH4 is evaluated. Discussion
      of the transfer of these experiences to the possibility of treating mothers at
      risk for maternal PKU is presented. RESULTS: In 41 patients with PKU/HPA, we
      found 17 (41%) bearing at least 1 allele with a mutation described as being
      responsive to BH4. In 8 of the patients, BH4 loading had been performed in the
      newborn period, in 6 of whom the test showed a clear decrease of blood Phe 4 and
      8 hours after loading. One of the nonresponders was reinvestigated at 3 years of
      age, showing a clear response (genotype Y414C/R408W): BH4 supplementation
      resulted in a much higher Phe tolerance (500 instead of 250 mg/day) with blood
      Phe levels <200 micromol/L. Two children (genotype E390G/IVS10-11g>a and
      L48S/L48S, respectively) were treated with BH4 only (15-20 mg/kg body
      weight/day), one from birth, the other from 2 years of age. Blood Phe decreased
      from >800 micromol/L to a mean of 321.4 and 331.7 micromol/L, respectively
      (range: 141-718 micromol/L) under a normal diet (total observation time: 4
      years). Development was normal with no adverse reactions. CONCLUSIONS: BH4
      supplementation seems to be a promising alternative treatment in some patients
      with mild PKU. Because blood Phe levels in maternal PKU should be maintained at
      120 to 360 micromol/L, clinical relevance may be even greater than for treatment
      of children with PKU/HPA. BH4 supplementation may also be combined with a Phe
      restricted diet, allowing higher Phe intake and protecting mothers from high Phe
      blood peaks. However, additional studies are necessary to prove the safety and
      economy of such an alternative treatment in patients with PKU/HPA, especially
      during pregnancy.

PMID- 14654667
TI  - Future role of large neutral amino acids in transport of phenylalanine into the
      brain.
AB  - OBJECTIVE: The treatment of phenylketonuria (PKU) in children and adults has been
      difficult because of erosion of dietary adherence, leading to poor school
      performance, impairment of executive functioning, loss of IQ, and deterioration
      of white matter in the brain. Mutant PKU mice produced by exposure to N-ethyl-N'
      nitrosourea (ENU) were used to examine the effect of large neutral amino acid
      (LNAA) supplementation on brain and blood phenylalanine (Phe). METHODS: Mice with
      PKU, genotype ENU 2/2 with features of classical PKU, were supplemented with LNAA
      while on a normal diet. Two dosages of LNAA were given 0.5 g/kg and 1.0 g/kg by
      gavage. Blood Phe was determined in the experimental, control, and sham-treated
      mice. Brain Phe was determined by magnetic resonance spectroscopy after
      perchloric acid extraction. Branched-chain amino acid transferase (BCAT) was
      determined in brain as a marker for energy metabolism. RESULTS: Blood Phe was
      reduced in the LNAA-treated mice by an average of 15% (0.5 g/kg) and 50% (1.0
      g/kg) in 48 hours. There was a sustained decrease in the blood Phe levels over a
      6-week trial. The untreated mice and sham-treated mice maintained high blood Phe
      throughout the experiments. Brain Phe level determined by magnetic resonance
      spectroscopy showed a decline of 46% after the LNAA treatment. BCAT levels were
      lower (33%) in the ENU 2/2 mice compared with wild-type. The BCAT normalized in
      mice with PKU that were treated with LNAA. CONCLUSION: The results suggest that
      giving LNAA lowered brain and blood Phe levels in mice with PKU. Energy
      metabolism generated from BCAT also improved in mice with PKU after treatment
      with LNAA. Data from the mice suggest that LNAA should be considered among the
      strategies to treat PKU in humans.

PMID- 14654669
TI  - Brain imaging and proton magnetic resonance spectroscopy in patients with
      phenylketonuria.
AB  - Magnetic resonance imaging studies in patients with phenylketonuria (PKU)
      revealed white matter alterations that correlated to most recent blood
      phenylalanine (Phe) concentrations as well as to brain Phe concentrations
      measured by magnetic resonance spectroscopy. The clinical significance of these
      changes is unknown. Magnetic resonance imaging data thus have no impact on
      therapeutic recommendations for adolescents and adults with PKU. Kinetic
      investigations of patients by magnetic resonance spectroscopy showed differences
      in brain Phe concentrations despite similar blood Phe levels. These were
      influenced by interindividual variations of blood-brain barrier Phe transport
      constants and by variations of the individual brain Phe consumption rate. Blood
      brain barrier Phe transport characteristics as well as brain Phe consumption
      rates thus seem to be causative factors for the individual outcome in PKU.

PMID- 14654668
TI  - Brain phenylalanine concentrations in phenylketonuria: research and treatment of
      adults.
AB  - OBJECTIVE: To assess the effects of 2 pharmacologic interventions (amino acid
      supplements) on the brain levels of phenylalanine (Phe) in adults with
      phenylketonuria (PKU). METHODS: A prospective study was conducted in an
      outpatient treatment and follow-up setting. The volunteers who were recruited for
      the first intervention included 4 subjects with classic PKU. The second
      intervention included 3 adults with classic PKU. The first intervention consisted
      of dietary supplementation during 1 day with Phlexy 10. Two individuals were
      given a dose of 0.5 g/kg/d, and 2 were given 1.0 g/kg/d. The second intervention
      consisted of dietary supplementation with PreKUnil at 0.4 g kg/d over a period of
      6 months. Brain Phe was measured by magnetic resonance spectroscopy. The number
      of the patients involved precluded analysis for significance. RESULTS: The first,
      shorter intervention resulted in a decrease in brain Phe. The second intervention
      resulted in a 20% decrease in brain Phe, which was maintained after 6 months of
      treatment. CONCLUSION: Dietary supplementation of large neutral amino acids seems
      to lower the brain Phe in adults who have PKU and have difficulty following their
      diet.

PMID- 14654670
TI  - The Maternal Phenylketonuria Project: a summary of progress and challenges for
      the future.
AB  - The results of the International Collaborative Study of Maternal phenylketonuria
      have shown that dietary phenylalanine restriction of women with
      hyperphenylalaninemia during pregnancy decreases the incidence of mental
      retardation, microcephaly, congenital heart disease, and intrauterine growth
      retardation in their offspring. The best results are achieved when treatment is
      initiated before conception. Psychosocial problems are the most pervasive
      obstacle to the achievement of optimum dietary treatment. Novel, nondietary
      approaches to the treatment of maternal phenylketonuria are under development.

PMID- 14654672
TI  - Who's enrolled in the State Children's Health Insurance Program (SCHIP)? An
      overview of findings from the Child Health Insurance Research Initiative (CHIRI).
AB  - BACKGROUND: The State Children's Health Insurance Program (SCHIP) was enacted in
      1997 to provide health insurance coverage to uninsured low-income children from
      families who earned too much to be eligible for Medicaid. OBJECTIVES: To develop
      a "baseline" portrait of SCHIP enrollees in 5 states (Alabama, Florida, Kansas,
      Indiana, and New York) by examining: 1) SCHIP enrollees' demographic
      characteristics and health care experiences before enrolling in SCHIP,
      particularly children with special health care needs (CSHCN), racial and ethnic
      minority children, and adolescents; 2) the quality of the care adolescents
      received before enrollment; and 3) the changes in enrollee characteristics as
      programs evolve and mature. METHODS: Each of 5 projects from the Child Health
      Insurance Research Initiative (CHIRI) surveyed new SCHIP enrollees as identified
      by state enrollment data. CHIRI investigators developed the CHIRI common core (a
      set of survey items from validated instruments), which were largely incorporated
      into each survey. Bivariate and multivariate analyses were conducted to ascertain
      whether there were racial and ethnic disparities in access to health care and
      differences between CSHCN and those without. Current Population Survey data for
      New York State were used to identify secular trends in enrollee characteristics.
      RESULTS: Most SCHIP enrollees (65% in Florida to 79% in New York) resided in
      families with incomes < or =150% of the federal poverty level. Almost half of
      SCHIP enrollees lived in single-parent households. A majority of SCHIP parents
      had not had education beyond high school, and in 2 states (Alabama and New York)
      approximately 25% had not completed high school. The vast majority of children
      lived in households with a working adult, and in a substantial proportion of
      households both parents worked. Children tended to be either insured for the
      entire 12 months or uninsured the entire 12 months before enrolling in SCHIP.
      Private insurance was the predominant form of insurance before enrollment in
      SCHIP in most states, but 23.3% to 51.2% of insured children had Medicaid as
      their most recent insurance. HEALTH CARE USE AND UNMET NEEDS BEFORE SCHIP: The
      vast majority of all SCHIP enrollees had a usual source of care (USC) during the
      year before SCHIP. The proportion of children who changed their USC after
      enrolling in SCHIP ranged from 29% to 41.3%. A large proportion of SCHIP
      enrollees used health services during the year before SCHIP, with some
      variability across states in the use of health care. Nevertheless, 32% to almost
      50% of children reported unmet needs. CSHCN: The prevalence of CSHCN in SCHIP
      (between 17% and 25%) in the study states was higher than the prevalence of CSHCN
      reported in the general population in those states. In many respects, CSHCN were
      similar to children without special health care needs, but CSHCN had poorer
      health status, were more likely to have had unmet needs, and were more likely to
      use the emergency department, mental health care, specialty care, and acute care
      in the year before enrolling in SCHIP than children without special health care
      needs. RACE AND ETHNICITY: A substantial proportion of SCHIP enrollees were black
      non-Hispanic or Hispanic children (Alabama: 34% and <1%; Florida: 6% and 26%;
      Kansas: 12% and 15%; and New York: 31% and 45%, respectively). Minority children
      were poorer, in poorer health, and less likely to have had a USC or private
      insurance before enrolling in SCHIP. The prevalence and magnitude of the
      disparities varied among the states. QUALITY OF CARE FOR ADOLESCENTS: Seventy
      three percent of adolescent SCHIP enrollees engaged in one or more risk behaviors
      (ie, feeling sad or blue; alcohol, tobacco, and drug use; having sexual
      intercourse; and not wearing seat belts). Although almost 70% of adolescents
      reported having had a preventive care visit the previous year, a majority of them
      did not receive counseling in each of 4 counseling areas. Controlling for other
      factors, having a private, confidential visit with the physician was associated
      with an increased liked likelihood (2-3 times more likely) that the adolescent
      received counseling for 3 of 4 counseling areas. TRENDS OVER TIME: New York SCHIP
      enrollees in 2001, compared with 1994 enrollees in New York's SCHIP-precursor
      child health insurance program, were more likely to be black or Hispanic, older,
      from New York City, and from families with lower education, income, and
      employment levels. A greater proportion of 2001 enrollees was uninsured for some
      time in the year before enrollment, was insured by Medicaid, and lacked a USC.
      Secular trends in the low-income population in the state did not seem to be
      responsible for these differences. Program modifications during this time period
      that may be related to the shift in enrollee characteristics include changes to
      benefits, outreach and marketing efforts, changes in the premium structure, and
      the advent of a single application form for multiple public programs.
      CONCLUSIONS: SCHIP enrollees are a diverse group, and there was considerable
      variation among the 5 study states. Overall, SCHIP enrollees had substantial and
      wide-ranging health care needs despite high levels of prior contact with the
      health care system. A sizable minority of SCHIP enrollees has special health care
      needs. There is racial and ethnic diversity in the composition of enrollees as
      well, with racial and ethnic disparities present. The quality of care adolescents
      received before enrollment in SCHIP was suboptimal, with many reporting unmet
      health care needs and not receiving recommended counseling. The characteristics
      of SCHIP enrollees can be expected to change as SCHIP programs evolve and mature.
      POLICY IMPLICATIONS: 1) Benefits should be structured to meet the needs of SCHIP
      enrollees, which are comparable to Medicaid enrollees' needs in many respects. 2)
      Provider networks will have to be broad if continuity of care is to be achieved.
      3) Multiple outreach strategies should be used, including using providers to
      distribute information about SCHIP. 4) The quality of care delivered to
      vulnerable populations (eg, minority children, CSHCN, and adolescents) should be
      monitored. 5) States and health plans should actively promote quality health care
      with the goal of improving the care received by SCHIP enrollees before
      enrollment. 6) States will have to craft policies that fit their local context.
      7) Collecting baseline information on SCHIP enrollees on a continuous basis is
      important, because enrollee characteristics and needs can change, and many
      vulnerable children are enrolling in SCHIP.

PMID- 14654673
TI  - Children with special health care needs enrolled in the State Children's Health
      Insurance Program (SCHIP): patient characteristics and health care needs.
AB  - BACKGROUND: Children with special health care needs (CSHCN) often require more
      extensive services than children without special needs. The State Children's
      Health Insurance Program (SCHIP) in many states typically provides less extensive
      benefits and services than do state Medicaid programs. To design SCHIP to address
      the needs of CSHCN adequately, it is important to measure the degree to which
      children who enroll in SCHIP have special health care needs and to assess their
      health status and unmet health care needs. Little is known about the
      characteristics or preenrollment experience of CSHCN who enroll in SCHIP.
      OBJECTIVES: To use data from the Child Health Insurance Research Initiative to
      measure the prevalence of CSHCN in SCHIP in 4 states, describe their demographic
      and health care features at enrollment, and compare their sociodemographic
      characteristics, health status, prior health care experiences, and unmet needs
      versus children without special health care needs. METHODS: Children (0-18 years
      old) newly enrolled in SCHIP in 4 states were eligible for the study: New York,
      Florida (adolescents only), Kansas, and Indiana (CSHCN only). Telephone
      interviews were conducted shortly after enrollment and identified CSHCN by using
      the Child and Adolescent Health Measurement Initiative CSHCN screener. A common
      set of core questions assessed demographic characteristics, health status,
      special health care need status, insurance experience, access, use, quality of
      health care, and unmet needs during the year before enrollment. Bivariate and
      multivariate analyses were used to compare characteristics of CSHCN with
      characteristics of children without special needs. RESULTS: Interviews were
      completed for parents of 5296 children enrolled in SCHIP in the 4 states. By
      using the Child and Adolescent Health Measurement Initiative CSHCN screener, the
      prevalence of CSHCN among SCHIP enrollees was 17% (New York), 18% (Florida), and
      25% (Kansas), higher than the prevalence of CSHCN reported in the general
      population in those states. More than half of CSHCN reported the use of a chronic
      medication. Demographic characteristics of CSHCN were similar to those of
      children without special needs, although CSHCN were more likely to reside in
      single-parent households. Although CSHCN had poorer health status than children
      without special needs, many CSHCN were reported to be in good health, suggesting
      a wide spectrum of severity of illnesses within the CSHCN group. Although CSHCN
      were more likely than children without special needs to have been insured before
      SCHIP, a large proportion of CSHCN were nevertheless uninsured for at least 12
      months before SCHIP (New York, 56%; Florida, 68%; Kansas, 24%; Indiana, 25%).
      Although most SCHIP enrollees had a usual source of care (USC) before SCHIP and
      there was some variation across states, between 4% and 13% of CSHCN lacked a USC
      on enrollment, and 23% to 38% of CSHCN changed their USC after enrollment in
      SCHIP. The majority of all SCHIP enrollees (including CSHCN) had used some health
      care during the year before SCHIP including preventive, acute, or specialty care.
      A high proportion of all SCHIP enrollees, including >30% to 40% of CSHCN, were
      reported to have unmet health care needs at enrollment in SCHIP. A variety of
      unmet needs were reported by CSHCN including specialty care, mental health care,
      dental care, and prescription medications. Nevertheless, the vast majority of
      CSHCN as well as children without special needs rated the quality of their
      medical care before SCHIP highly on several specific quality measures. Findings
      from multivariate analyses were similar to bivariate results with CSHCN in
      several states having higher use of care and more unmet health care needs before
      enrollment. CONCLUSIONS: SCHIP is enrolling many CSHCN, with the prevalence of
      these children occurring at least as high as the prevalence of CSHCN in the
      general population. CSHCN enrolled in SCHIP represent a heterogeneous population
      with a wide range of health status and health care needs. Although most CSHCN
      were already already connected to the health care system with a USC and prior
      health care visits, many had unmet health care needs before enrolling in SCHIP.
      IMPLICATIONS FOR MONITORING AND IMPROVING SCHIP FOR CSHCN ENROLLEES: 1) SCHIP
      benefit packages need to adequately cover services required by CSHCN such as
      prescription medications and specialty, mental health, developmental, and home
      services; 2) because utilization of care will be high among this large group of
      children, alternative methods of financing and managing care should be considered
      such as risk adjustment and special programs that involve case management and
      care coordination; 3) coordination of care across programs (such as between SCHIP
      and the state Title V Maternal and Child Health Services program, a component of
      which serves CSHCN) and ensuring adequate access to primary care and specialty
      providers might improve access to services for CSHCN; and 4) it is critical to
      monitor the quality of care for CSHCN enrolled in SCHIP, because these children
      are among the most vulnerable children covered by public health insurance
      programs and many of them are enrolling in SCHIP.

PMID- 14654674
TI  - The role of race and ethnicity in the State Children's Health Insurance Program
      (SCHIP) in four states: are there baseline disparities, and what do they mean for
      SCHIP?
AB  - BACKGROUND: Elimination of racial and ethnic disparities in health has become a
      major national goal. The State Children's Health Insurance Program (SCHIP) has
      the potential to reduce disparities among the children who enroll if they exhibit
      the same disparities that have been documented in previous studies of low-income
      children. To determine the potential impact of SCHIP on racial and ethnic
      disparities, it is critical to assess baseline levels of health disparities among
      children enrolling in SCHIP. OBJECTIVE: To use data from the Child Health
      Insurance Research Initiative (CHIRI) to 1) describe the sociodemographic profile
      of new enrollees in SCHIP in Alabama, Florida, Kansas, and New York; 2) determine
      if there were differences in health insurance and health care experiences among
      white, black, and Hispanic SCHIP enrollees before enrollment in SCHIP; and 3)
      explore whether race or ethnicity, controlled for other factors, affected pre
      SCHIP access to health coverage and health care. SETTING: SCHIP programs in
      Alabama, Florida, Kansas, and New York, which together include 26% of SCHIP
      enrollees nationwide. DESIGN: Telephone interview (mailed survey in Alabama)
      about the child's health, health insurance, and health care experiences conducted
      shortly after SCHIP enrollment to assess experience during the time period before
      SCHIP. SAMPLE: New SCHIP enrollees (0-17.9 years old in Alabama, Kansas, and New
      York and 11.5-17.9 years old in Florida). Stratified sampling was performed in
      Kansas and New York, with results weighted to reflect statewide populations of
      new SCHIP enrollees. MEASURES: Sociodemographic characteristics including income,
      education, employment, and other characteristics of the child and the family,
      race and ethnicity (white non-Hispanic, black non-Hispanic, and Hispanic [any
      race]), prior health insurance, health care access and utilization, and health
      status. ANALYSES: Bivariate analyses were used to compare baseline measures upon
      enrollment for white, black, and Hispanic SCHIP enrollees. Multivariate analyses
      were performed to assess health status and health care access measures (prior
      insurance, presence of a usual source of care (USC), and use of preventive care),
      controlling for demographic factors described above. Weighted analyses (where
      appropriate) were performed by using SPSS, STATA, or SUDAAN. RESULTS: Racial and
      ethnic composition varied across the SCHIP cohorts studied, with black and
      Hispanic children comprising the following proportion of enrollees, respectively:
      Alabama, 33% and <1%; Florida, 16% and 26%; Kansas, 12% and 15%; and New York,
      24% and 36%. Black and Hispanic children were more likely to reside in single
      parent and lower-income families. With some variation by state, children from
      minority groups were more likely to report poorer health status than were white
      children. Relative to white children, children from minority groups in Florida
      and New York were more likely to have been uninsured for the entire year before
      SCHIP enrollment. In all states, children from minority groups who had prior
      coverage were more likely to have previously been enrolled in Medicaid than in
      private health insurance and were less likely to have had employer-sponsored
      coverage compared with white children. Except in Alabama, there was a difference
      in having a USC, with children from minority groups less likely to have had a USC
      before SCHIP enrollment compared with white children. No consistent pattern of
      health care utilization before SCHIP was noted across states with respect to race
      or ethnicity. Findings from multivariate analyses, controlling for
      sociodemographic factors, generally confirmed that black and Hispanic children
      were more likely to have lacked insurance or a USC before enrollment in SCHIP and
      to have poorer health status compared with white children. CONCLUSIONS: SCHIP is
      enrolling substantial numbers of racial and ethnic minority children. There are
      baseline racial and ethnic disparities among new enrollees in SCHIP, with black
      and Hispanic children faring worse than white children on many sociodemographic
      and health system measures, and there are differences among states in the
      prevalence and magnitude of these disparities. After controlling for
      sociodemographic factors, these disparities persisted. IMPLICATIONS FOR
      MONITORING AND IMPROVING SCHIP: SCHIP has the potential to play a critical role
      in efforts to eliminate racial and ethnic disparities in health among the
      children it serves. However, study findings indicate that programmatic efforts
      are necessary to ensure that disparities are not perpetuated. Program
      effectiveness and outcomes should be monitored by race and ethnicity to ensure
      equity in access, use, and outcomes across all racial and ethnic groups.
      Assessing the health characteristics and needs of new SCHIP enrollees can provide
      a benchmark for evaluating the program's impact on eliminating racial and ethnic
      disparities in health and inform service delivery enhancements.

PMID- 14654675
TI  - Adolescents' preventive care experiences before entry into the State Children's
      Health Insurance Program (SCHIP).
AB  - BACKGROUND: Adolescence has traditionally been thought of as a time of good
      health. However, adolescents comprise an important group with unique needs among
      State Children's Health Insurance Program (SCHIP) enrollees. Throughout the
      1990s, there was increasing evidence of unacceptably high morbidity and mortality
      among adolescents from injuries, suicide, sexually transmitted diseases,
      substance abuse, and other conditions associated with risk behaviors. The
      establishment of relationships with the health care system can ensure prompt
      treatment and help promote healthy behaviors, assuming that the adolescent feels
      comfortable seeking help for his or her health-related concerns. However, health
      care systems typically are not designed to ensure that adolescents receive the
      primary and preventive care that might ameliorate the negative consequences of
      health-damaging behaviors. OBJECTIVES: The purpose of this study was to examine
      the following hypotheses. 1) Adolescents with special health care needs, those
      engaging in risk behaviors, and those who were insured before program enrollment
      would be more likely than those who were healthy and those not engaging in risk
      behaviors to have a preventive care visit in the year preceding the interview. No
      differences would be observed in the odds of preventive care visits based on age,
      race/ethnicity, and gender. 2) No differences would be observed in the receipt of
      risk-behavior counseling for those with a preventive care visit based on the
      adolescents' sociodemographic and health characteristics. 3) Adolescents who were
      older would be more likely to engage in risk behaviors than younger adolescents.
      There would be no differences in reports of risk behaviors based on gender,
      race/ethnicity, and children with special health care needs status. METHODS:
      Adolescents 12 to 19 years old and newly enrolled in SCHIP were eligible for the
      study. Telephone interviews were conducted within 3 months after enrollment with
      parents of adolescents to obtain sociodemographic information and information
      about the adolescents' health by using the Children with Special Health Care
      Needs screener. Interviews also were conducted with the adolescents themselves to
      obtain information about the adolescents' risk behaviors and experiences with
      preventive care before SCHIP enrollment. RESULTS: Interviews were completed with
      1872 parents. In addition, a total of 918 interviews were completed with
      adolescents. Approximately 73% of adolescents reported engaging in at least one
      risk behavior. Approximately 69% reported having a primary care visit during the
      last year with 46% of those reporting that the visit was private. Of those
      reporting a primary care visit, between 41% and 53% reported receiving counseling
      along 1 of the 5 content dimensions of anticipatory guidance. Older adolescents
      were more likely to engage in risk behaviors than younger adolescents. Hispanic
      adolescents were approximately 30% less likely than white non-Hispanic
      adolescents to report engaging in risk behaviors. In terms of having a preventive
      care visit, adolescents with a special need were twice as likely to have a visit
      when compared with their healthy counterparts. Hispanics and black non-Hispanics
      were half as likely to have a preventive care visit (odds ratios of 0.59 and
      0.54, respectively) than white non-Hispanics. Those engaging in risk behaviors
      were almost 50% less likely to report private preventive care visits than those
      reporting no risk behaviors. Privacy during the preventive care visit was
      associated with a greater odds of receiving counseling for risk behaviors in
      general, sexual activity, and emotional health and relationships. Depending on
      the type of counseling, those with private preventive care visits were 2 to 3
      times more likely to receive the counseling than those whose visits were not
      private. In addition, those engaging in risk behaviors were 1.45 to almost 2
      times more likely to receive counseling than those not engaging in any risk
      behaviors. CONCLUSIONS AND IMPLICATIONS: Based on our findings, health plans
      health plans and providers involved in SCHIP are likely to serve adolescents who
      have had limited opportunities for private preventive care visits and counseling
      during such visits. The most underserved are likely to be black and Hispanic
      adolescents who may have had no preventive care at all compared with their white
      non-Hispanic counterparts. State agencies, health plans, and providers need to
      follow established guidelines for adolescent health care that emphasize the
      provision of counseling for risk behaviors for all adolescents, not just those
      engaging in risk behaviors or those with special health care needs. Moreover,
      providers need to seek opportunities to ensure privacy for the adolescents during
      their preventive care visits so that much-needed counseling can be provided.
      Particular attention needs to be given to adolescents from minority groups to
      encourage them to seek preventive care.

PMID- 14654676
TI  - The evolution of the State Children's Health Insurance Program (SCHIP) in New
      York: changing program features and enrollee characteristics.
AB  - BACKGROUND: The State Children's Health Insurance Program (SCHIP) has been
      operating for >5 years. Policy makers are interested in the characteristics of
      children who have enrolled and changes in the health care needs of enrolled
      children as programs mature. New York State's SCHIP evolved from a similar
      statewide health insurance program that was developed in 1991 (Child Health Plus
      [CHPlus]). Understanding how current SCHIP enrollees differ from early CHPlus
      enrollees together with how program features changed during the period may shed
      light on how best to serve the evolving SCHIP population. OBJECTIVE: To 1)
      describe changes in the characteristics of children enrolled in 1994 CHPlus and
      2001 SCHIP; 2) determine if changes in the near-poor, age-eligible population
      during the time period could account for the evolution of enrollment; and 3)
      describe changes in the program during the period that could be responsible for
      the enrollment changes. SETTING: New York State, stratified into 4 regions: New
      York City, New York City environs, upstate urban counties, and upstate rural
      counties. DESIGN: Retrospective telephone interviews of parents of 2 cohorts of
      CHPlus enrollees: 1) children who enrolled in CHPlus in 1993 to 1994 and 2)
      children who enrolled in New York's SCHIP in 2000 to 2001. The Current Population
      Survey (CPS) 1992 to 1994 and 1999 to 2001 were used to identify secular trends
      that could explain differences in the CHPlus and SCHIP enrollees. PROGRAM
      CHARACTERISTICS: 1994 CHPlus and 2001 SCHIP were similar in design, both limiting
      eligibility by age, family income, and insurance status. SCHIP 2001 included 1)
      expansion of eligibility to adolescents 13 to 19 years old; 2) expansion of
      benefits to include hospitalizations, mental health, and dental benefits; 3)
      changes in premium contributions; 4) more participating insurance plans, limited
      to managed care; 5) expansions in marketing and outreach; and 6) a combined
      enrollment application for SCHIP and several low-income programs including
      Medicaid. SAMPLE: Cohort 1 included 2126 new CHPlus enrollees 0 to 13 years old
      who were enrolled for at least 9 months, stratified by geographic region. Cohort
      2 included 1100 new SCHIP enrollees 0 to 13 years old who were enrolled for at
      least 9 months, stratified by geographic region, age, race, and ethnicity.
      Results were weighted to be representative of statewide CHPlus or SCHIP new
      enrollees who met the sampling criteria. Samples of age- and income-eligible
      children from New York State were drawn from the CPS and pooled and reweighted
      (1992-1994 and 1999-2001) to generate a comparison group of children targeted by
      CHPlus and SCHIP. MEASURES: Sociodemographic characteristics, race and ethnicity
      (white non-Hispanic, black non-Hispanic, and Hispanic), prior health insurance,
      health care access, and first source of information about the program. ANALYSES:
      Weighted bivariate analyses (comparisons of means and rates) adjusted for the
      complex sampling design to compare measures between the 2 program cohorts and
      between the 2 CPS samples. We tested for equivalence by using chi2 statistics.
      RESULTS: As the program evolved from CHPlus to SCHIP, relatively more black and
      Hispanic children enrolled (9% to 30% black from 1994 to 2001, and 16% to 48%
      Hispanic), more New York City residents (46% to 69% from 1994 to 2001), more
      children with parents who had less than a high school education (10% to 25%),
      more children from lower income families (59% to 75% below 150% of the federal
      poverty level), and more children from families with parents not working (7% to
      20%) enrolled. These socioeconomic and demographic changes were not reflected in
      the underlying age- and income-eligible population. A greater proportion of 2001
      enrollees were uninsured for some time immediately before enrollment (57% to 76%
      had an uninsured gap), were insured by Medicaid during the year before enrollment
      (23% to 48%), and lacked a USC (5% to 14%). Although "word of mouth" was the most
      common means by which families heard about both programs, a greater proportion of
      2001 enrollees learned about SCHIP from marketing or outreach sources.
      CONCLUSION: As New York programs for the uninsured evolved, more children from
      minority groups, with lower family incomes and education, and having less
      baseline access to health care were enrolled. Although changes in the underlying
      population were relatively small, progressively increased marketing and outreach,
      particularly in New York City, the introduction of a single application form for
      SCHIP and Medicaid, and expansions in the benefit package may have accounted, in
      part, for the large change in the characteristics of enrollees.

PMID- 14654677
TI  - Low-income children and health insurance: old news and new realities.

PMID- 14654681
TI  - Tracking EcoKI and DNA fifty years on: a golden story full of surprises.
AB  - 1953 was a historical year for biology, as it marked the birth of the DNA helix,
      but also a report by Bertani and Weigle on 'a barrier to infection' of
      bacteriophage lambda in its natural host, Escherichia coli K-12, that could be
      lifted by 'host-controlled variation' of the virus. This paper lay dormant till
      Nobel laureate Arber and PhD student Dussoix showed that the lambda DNA was
      rejected and degraded upon infection of different bacterial hosts, unless it
      carried host-specific modification of that DNA, thus laying the foundations for
      the phenomenon of restriction and modification (R-M). The restriction enzyme of
      E.coli K-12, EcoKI, was purified in 1968 and required S-adenosylmethionine
      (AdoMet) and ATP as cofactors. By the end of the decade there was substantial
      evidence for a chromosomal locus hsdK with three genes encoding restriction (R),
      modification (M) and specificity (S) subunits that assembled into a large complex
      of >400 kDa. The 1970s brought the message that EcoKI cut away from its DNA
      recognition target, to which site the enzyme remained bound while translocating
      the DNA past itself, with concomitant ATP hydrolysis and subsequent double-strand
      nicks. This translocation event created clearly visible DNA loops in the electron
      microscope. EcoKI became the archetypal Type I R-M enzyme with curious DNA
      translocating properties reminiscent of helicases, recognizing the bipartite
      asymmetric site AAC(N6)GTGC. Cloning of the hsdK locus in 1976 facilitated
      molecular understanding of this sophisticated R-M complex and in an elegant 'pas
      de deux' Murray and Dryden constructed the present model based on a large body of
      experimental data plus bioinformatics. This review celebrates the golden
      anniversary of EcoKI and ends with the exciting progress on the vital issue of
      restriction alleviation after DNA damage, also first reported in 1953, which
      involves intricate control of R subunit activity by the bacterial proteasome
      ClpXP, important results that will keep scientists on the EcoKI track for another
      50 years to come.

PMID- 14654682
TI  - In vitro characterization of a base pairing interaction between the primer
      binding site and the minimal packaging signal of avian leukosis virus genomic
      RNA.
AB  - The 5' leader region of avian sarcoma-leukosis viruses (ASLVs) folds into a
      series of RNA secondary structures which are involved in key steps in the viral
      replication cycle such as reverse transcription, dimerization and packaging of
      genomic RNA. The O3 stem and three stem-loops (O3SLa, O3SLb and O3SLc) form the
      minimal packaging signal that is located downstream of the primer binding site
      (PBS). The U5-PBS region contributes to packaging via a mechanism that remains
      unknown. In this in vitro study, we have investigated the possibility of
      interactions between the R-U5-PBS region and the minimal packaging signal using
      chemical and enzymatic probing, antisense oligonucleotides and site-directed
      mutagenesis. We have identified a base pairing interaction between the PBS
      sequence and the terminal loop of O3SLa. It was found that the PBS/O3SLa
      interaction was intramolecular since it occurred not only in dimeric RNA but also
      in monomeric RNA. This interaction probably corresponds to a pseudoknot
      interaction. The PBS/O3SLa interaction may be formed in vivo since the sequences
      are highly conserved in ASLV strains. The PBS/O3SLa interaction may regulate the
      processes of primer tRNA annealing, packaging and initiation of Gag translation
      through its involvement in leader tertiary structure. Interestingly, we found
      that in other retroviruses the PBS sequence can also base pair with a terminal
      loop of the stem-loops involved in RNA packaging.

PMID- 14654683
TI  - HMG-D and histone H1 alter the local accessibility of nucleosomal DNA.
AB  - There is evidence that HMGB proteins facilitate, while linker histones inhibit
      chromatin remodelling, respectively. We have examined the effects of HMG-D and
      histone H1/H5 on accessibility of nucleosomal DNA. Using the 601.2 nucleosome
      positioning sequence designed by Widom and colleagues we assembled nucleosomes in
      vitro and probed DNA accessibility with restriction enzymes in the presence or
      absence of HMG-D and histone H1/H5. For HMG-D our results show increased
      digestion at two spatially adjacent sites, the dyad and one terminus of
      nucleosomal DNA. Elsewhere varying degrees of protection from digestion were
      observed. The C-terminal acidic tail of HMG-D is essential for this pattern of
      accessibility. Neither the HMG domain by itself nor in combination with the
      adjacent basic region is sufficient. Histone H1/H5 binding produces two sites of
      increased digestion on opposite faces of the nucleosome and decreased digestion
      at all other sites. Our results provide the first evidence of local changes in
      the accessibility of nucleosomal DNA upon separate interaction with two linker
      binding proteins.

PMID- 14654684
TI  - Molecular genetic analysis of chloroplast gene promoters dependent on SIG2, a
      nucleus-encoded sigma factor for the plastid-encoded RNA polymerase, in
      Arabidopsis thaliana.
AB  - Most photosynthesis-related genes in mature chloroplasts are transcribed by a
      eubacterial-type RNA polymerase (PEP) whose core subunits are encoded by the
      plastid genome. It has been shown previously that six putative nuclear genes
      (SIG1 to SIG6) encode promoter-specificity factors for PEP in Arabidopsis
      thaliana, and we isolated a T-DNA insertion line of SIG2 (sig2-1 mutant) that
      manifests aberrant chloroplast development. With the use of S1 nuclease
      protection and primer extension analyses, we have now characterized the SIG2
      dependent chloroplast promoters in A.thaliana. The amounts of transcripts derived
      from one of the multiple psbD promoters (psbD -256) and from the promoters of two
      tRNA genes (trnE-UUC and trnV-UAC) were markedly and specifically decreased in
      the sig2-1 mutant. The abundance of these transcripts was restored to wild-type
      levels by introduction into the mutant of a SIG2 transgene. The recombinant SIG2
      protein mixed with Escherichia coli core RNA polymerase could bind to a DNA
      fragment that contains the SIG2-dependent psbD -256, trnE-UUC or trnV-UAC
      promoter. Sequences similar to those of the -35 and -10 promoter elements of
      E.coli were identified in the regions of the SIG2-dependent chloroplast genes
      upstream of the transcription initiation sites.

PMID- 14654685
TI  - Visualization and interpretation of protein networks in Mycobacterium
      tuberculosis based on hierarchical clustering of genome-wide functional linkage
      maps.
AB  - Genome-wide functional linkages among proteins in cellular complexes and
      metabolic pathways can be inferred from high throughput experimentation, such as
      DNA microarrays, or from bioinformatic analyses. Here we describe a method for
      the visualization and interpretation of genome-wide functional linkages inferred
      by the Rosetta Stone, Phylogenetic Profile, Operon and Conserved Gene Neighbor
      computational methods. This method involves the construction of a genome-wide
      functional linkage map, where each significant functional linkage between a pair
      of proteins is displayed on a two-dimensional scatter-plot, organized according
      to the order of genes along the chromosome. Subsequent hierarchical clustering of
      the map reveals clusters of genes with similar functional linkage profiles and
      facilitates the inference of protein function and the discovery of functionally
      linked gene clusters throughout the genome. We illustrate this method by applying
      it to the genome of the pathogenic bacterium Mycobacterium tuberculosis,
      assigning cellular functions to previously uncharacterized proteins involved in
      cell wall biosynthesis, signal transduction, chaperone activity, energy
      metabolism and polysaccharide biosynthesis.

PMID- 14654686
TI  - Functional significance of intermediate cleavages in the 3'ETS of the pre-rRNA
      from Schizosaccharomyces pombe.
AB  - Pathways for the maturation of ribosomal RNAs are complex with numerous
      intermediate cleavage sites that are not always conserved closely in the course
      of evolution. Both in eukaryotes and bacteria genetic analyses and in vitro
      studies have strongly implicated RNase III-like enzymes in the processing of rRNA
      precursors. In Schizosacharomyces pombe, for example, the RNase III-like Pac1
      nuclease has been shown to cleave the free 3'ETS at two known intermediate sites
      but, in the presence of RAC protein, the same RNA also is cleaved at the 3'-end
      of the 25 S rRNA sequence. In this study normal and mutant 3'ETS sequences were
      digested with the Pac1 enzyme to further evaluate its role in rRNA processing.
      Accurate cleavage at the known intermediate processing sites was dependent on the
      integrity of the helical structure at these sites as well as a more distal upper
      stem region in the conserved extended hairpin structure of the 3'ETS. The
      cleavage of mutant 3'ETS sequences also generally correlated with the known
      effects of these mutations on rRNA production, in vivo. One mutant, however, was
      efficiently processed in vivo but was not a substrate for the Pac1 nuclease, in
      vitro. In contrast, in the presence of RAC protein, the same RNA remained
      susceptible to Pac1 nuclease cleavage at the 3'-end of the 25 rRNA sequence,
      indicating that the removal of the 3'ETS does not require cleavage at the
      intermediate sites. These results suggest that basic maturation pathways may be
      less complex than previously reported raising similar questions about other
      intermediate processing sites, which have been identified by analyses of termini,
      and/or processing, in vitro.

PMID- 14654687
TI  - Molecular model of SARS coronavirus polymerase: implications for biochemical
      functions and drug design.
AB  - The causative agent of severe acute respiratory syndrome (SARS) is a previously
      unidentified coronavirus, SARS-CoV. The RNA-dependent RNA polymerase (RdRp) of
      SARS-CoV plays a pivotal role in viral replication and is a potential target for
      anti-SARS therapy. There is a lack of structural or biochemical data on any
      coronavirus polymerase. To provide insights into the structure and function of
      SARS-CoV RdRp, we have located its conserved motifs that are shared by all RdRps,
      and built a three-dimensional model of the catalytic domain. The structural model
      permits us to discuss the potential functional roles of the conserved motifs and
      residues in replication and their potential interactions with inhibitors of
      related enzymes. We predict important structural attributes of potential anti
      SARS-CoV RdRp nucleotide analog inhibitors: hydrogen-bonding capability for the
      2' and 3' groups of the sugar ring and C3' endo sugar puckering, and the absence
      of a hydrophobic binding pocket for non-nucleoside analog inhibitors similar to
      those observed in hepatitis C virus RdRp and human immunodeficiency virus type 1
      reverse transcriptase. We propose that the clinically observed resistance of SARS
      to ribavirin is probably due to perturbation of the conserved motif A that
      controls rNTP binding and fidelity of polymerization. Our results suggest that
      designing anti-SARS therapies can benefit from successful experiences in design
      of other antiviral drugs. This work should also provide guidance for future
      biochemical experiments.

PMID- 14654688
TI  - Altered structural fluctuations in duplex RNA versus DNA: a conformational switch
      involving base pair opening.
AB  - DNA and RNA are known to have different structural properties. In the present
      study, molecular dynamics (MD) simulations on a series of RNA and DNA duplexes
      indicate differential structural flexibility for the two classes of
      oligonucleotides. In duplex RNA, multiple base pairs experienced local opening
      events into the major groove on the nanosecond time scale, while such events were
      not observed in the DNA simulations. Three factors are indicated to be
      responsible for the base opening events in RNA: solvent-base interactions,
      2'OH(n)-O4'(n+1) intra-strand hydrogen bonding, and enhanced rigid body motion of
      RNA at the nucleoside level. Water molecules in the major groove of RNA
      contribute to initiation of base pair opening. Stabilization of the base pair
      open state is due to a 'conformational switch' comprised of 2'OH(n)-O4'(n+1)
      hydrogen bonding and a rigid body motion of the nucleoside moiety in RNA. This
      rigid body motion is associated with decreased flexibility of the glycosyl
      linkage and sugar moieties in A-form structures. The observed opening rates in
      RNA are consistent with the imino proton exchange experiments for AU base pairs,
      although not for GC base pairs, while structural and flexibility changes
      associated with the proposed conformational switch are consistent with survey
      data of RNA and DNA crystal structures. The possible relevance of base pair
      opening events in RNA to its many biological functions is discussed.

PMID- 14654689
TI  - A novel allele of fission yeast rad11 that causes defects in DNA repair and
      telomere length regulation.
AB  - Replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding
      protein involved in DNA replication, recombination and repair. In Saccharomyces
      cerevisiae, several mutants in the RFA1 gene encoding the large subunit of RPA
      have been isolated and one of the mutants with a missense allele, rfa1-D228Y,
      shows a synergistic reduction in telomere length when combined with a yku70
      mutation. So far, only one mutant allele of the rad11(+) gene encoding the large
      subunit of RPA has been reported in Schizosaccharomyces pombe. To study the role
      of S.pombe RPA in DNA repair and possibly in telomere maintenance, we constructed
      a rad11-D223Y mutant, which corresponds to the S.cerevisiae rfa1-D228Y mutant.
      rad11-D223Y cells were methylmethane sulfonate, hydroxyurea, UV and gamma-ray
      sensitive, suggesting that rad11-D223Y cells have a defect in DNA repair
      activity. Unlike the S.cerevisiae rfa1-D228Y mutation, the rad11-D223Y mutation
      itself caused telomere shortening. Moreover, Rad11-Myc bound to telomere in a
      ChIP assay. These results strongly suggest that RPA is directly involved in
      telomere maintenance.

PMID- 14654690
TI  - The base pairing properties of 8-aza-7-deaza-2'-deoxyisoguanosine and 7
      halogenated derivatives in oligonucleotide duplexes with parallel and
      antiparallel chain orientation.
AB  - The base pairing properties of oligonucleotide duplexes containing 8-aza-7-deaza
      2'-deoxyisoguanosine, its 7-bromo or its 7-iodo derivative are described. The
      nucleosides were synthesized on a convergent route, protected and converted into
      phosphoramidites. Oligonucleotides were prepared on a solid-phase and were
      hybridized to yield duplexes with parallel (ps) or antiparallel (aps) chain
      orientation. The 8-aza-7-deaza-2'-deoxyisoguanosine-containing duplexes show
      almost identical base pairing stability as those containing 2'-deoxyisoguanosine,
      while the 7-substituted derivatives induce a significant duplex stabilization
      both in ps and aps DNA. Self-complementary duplexes with parallel chain
      orientation are exceptionally stable due to the presence of 5'-overhangs. The
      bulky halogen substituents were found to be well accommodated in the grooves both
      of aps and ps DNA.

PMID- 14654691
TI  - Effects of sequence on repeat expansion during DNA replication.
AB  - Small DNA repeat tracts are located throughout the human genome. The tracts are
      unstable, and expansions of certain repeat sequences cause neuromuscular disease.
      DNA expansions appear to be associated with lagging-strand DNA synthesis and DNA
      repair. At some sites of repeat expansion, e.g. the myotonic dystrophy type 2
      (DM2) tetranucleotide repeat expansion site, more than one repeat tract with
      similar sequences lie side by side. Only one of the DM2 repeat tracts, however,
      is found to expand. Thus, DNA base sequence is a possible factor in repeat tract
      expansion. Here we determined the expansion potential, during DNA replication by
      human DNA polymerase beta, of several tetranucleotide repeat tracts in which the
      repeat units varied by one or more bases. The results show that subtle changes,
      such as switching T for C in a tetranucleotide repeat, can have dramatic
      consequences on the ability of the nascent-strand repeat tract to expand during
      DNA replication. We also determined the relative stabilities of self-annealed
      100mer repeats by melting-curve analysis. The relative stabilities did not
      correlate with the relative potentials of the analogous repeats for expansion
      during DNA replication, suggesting that hairpin formation is not required for
      expansion during DNA replication.

PMID- 14654693
TI  - A new, but old, nucleoside analog: the first synthesis of 1-deaza-2'
      deoxyguanosine and its properties as a nucleoside and as oligodeoxynucleotides.
AB  - The first synthesis of 5-amino-3-(2'-deoxy-beta-D-ribofuranosyl)imidazo[4,5
      b]pyridin-7-one (1-deaza-2'-deoxyguanosine) is described. The compound was
      converted from the known AICA-deoxyriboside. The tautomeric structure of the base
      moiety was determined by theoretical calculation to be a hydroxyl form. Although
      the analog was found to be labile to acidic conditions, 1-deaza-2'-deoxyguanosine
      was successfully converted into a phosphoramidite derivative, which was
      incorporated into oligodeoxynucleotides by the standard phosphoramidite method.
      Thermal stabilities of oligodeoxynucleotides containing 1-deaza-2'-deoxyguanosine
      were investigated by thermal denaturing experiments. Also, a triphosphate analog
      of 1-deaza-2'-deoxyguanosine was synthesized for polymerase extension reactions.
      Single nucleotide insertion reactions using a template containing 1-deaza-2'
      deoxyguanosine, as well as 1-deaza-2'-deoxyguanosine triphosphate, were performed
      using the Klenow fragment (exonuclease minus) polymerase and other polymerases.
      No hydrogen bonded base pairs, even a 1-deaza-2'-deoxyguanosine:cytidine base
      pair, were indicated by thermal denaturing studies. However, though less
      selective and less effective than the natural guanosine counterpart, the
      polymerase extension reactions suggested the formation of a base pair of 1-deaza
      2'-deoxyguanosine with cytidine during the insertion reactions.

PMID- 14654692
TI  - Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional
      activity of ADD1/SREBP1c.
AB  - Adipocyte determination and differentiation dependent factor 1 (ADD1)/sterol
      regulatory element binding protein isoform (SREBP1c) is a key transcription
      factor in fatty acid metabolism and insulin- dependent gene expression. Although
      its transcriptional and post-translational regulation has been extensively
      studied, its regulation by interacting proteins is not well understood. To
      identify cellular proteins that associate with ADD1/SREBP1c, we employed the
      yeast two-hybrid system with an adipocyte cDNA library. Using the N-terminal
      domain of ADD1/SREBP1c as bait, we identified Twist2 (also known as Dermo-1), a
      basic helix-loop-helix (bHLH) protein, as a novel ADD1/SREBP1c interacting
      protein. Over-expression of Twist2 strongly repressed the transcriptional
      activity of ADD1/SREBP1c, primarily by reducing its binding to target sequences.
      Inhibition of histone deacetylase (HDAC) activity with HDAC inhibitors relieved
      this repression. Our data suggest that physical interaction between Twist2 and
      ADD1/SREBP1c attenuates transcriptional activation by ADD1/SREBP1c by inhibiting
      its binding to DNA, and that this inhibition is at least partly dependent on
      chromatin modification by HDACs.

PMID- 14654694
TI  - Using electrostatic potentials to predict DNA-binding sites on DNA-binding
      proteins.
AB  - A method to detect DNA-binding sites on the surface of a protein structure is
      important for functional annotation. This work describes the analysis of residue
      patches on the surface of DNA-binding proteins and the development of a method of
      predicting DNA-binding sites using a single feature of these surface patches.
      Surface patches and the DNA-binding sites were initially analysed for
      accessibility, electrostatic potential, residue propensity, hydrophobicity and
      residue conservation. From this, it was observed that the DNA-binding sites were,
      in general, amongst the top 10% of patches with the largest positive
      electrostatic scores. This knowledge led to the development of a prediction
      method in which patches of surface residues were selected such that they excluded
      residues with negative electrostatic scores. This method was used to make
      predictions for a data set of 56 non-homologous DNA-binding proteins. Correct
      predictions made for 68% of the data set.

PMID- 14654696
TI  - A conserved chloramphenicol binding site at the entrance to the ribosomal peptide
      exit tunnel.
AB  - The antibiotic chloramphenicol produces modifications in 23S rRNA when bound to
      ribosomes from the bacterium Escherichia coli and the archaeon Halobacterium
      halobium and irradiated with 365 nm light. The modifications map to nucleotides
      m(5)U747 and C2611/C2612, in domains II and V, respectively, of E.coli 23S rRNA
      and G2084 (2058 in E.coli numbering) in domain V of H.halobium 23S rRNA. The
      modification sites overlap with a portion of the macrolide binding site and
      cluster at the entrance to the peptide exit tunnel. The data correlate with the
      recently reported chloramphenicol binding site on an archaeal ribosome and
      suggest that a similar binding site is present on the E.coli ribosome.

PMID- 14654695
TI  - The linker histone homolog Hho1p from Saccharomyces cerevisiae represents a
      winged helix-turn-helix fold as determined by NMR spectroscopy.
AB  - Hho1p is assumed to serve as a linker histone in Saccharomyces cerevisiae and,
      notably, it possesses two putative globular domains, designated HD1 (residues 41
      118) and HD2 (residues 171-252), that are homologous to histone H5 from chicken
      erythrocytes. We have determined the three-dimensional structure of globular
      domain HD1 with high precision by heteronuclear magnetic resonance spectroscopy.
      The structure had a winged helix-turn-helix motif composed of an
      alphabetaalphaalphabetabeta fold and closely resembled the structure of the
      globular domain of histone H5. Interestingly, the second globular domain, HD2, in
      Hho1p was unstructured under physiological conditions. Gel mobility assay
      demonstrated that Hho1p preferentially binds to supercoiled DNA over linearized
      DNA. Furthermore, NMR analysis of the complex of a deletion mutant protein
      (residues 1-118) of Hho1p with a linear DNA duplex revealed that four regions
      within the globular domain HD1 are involved in the DNA binding. The above results
      suggested that Hho1p possesses properties similar to those of linker histones in
      higher eukaryotes in terms of the structure and binding preference towards
      supercoiled DNA.

PMID- 14654697
TI  - Substitutions at tyrosine 66 of Escherichia coli uracil DNA glycosylase lead to
      characterization of an efficient enzyme that is recalcitrant to product
      inhibition.
AB  - Uracil DNA glycosylase (UDG), a ubiquitous and highly specific enzyme, commences
      the uracil excision repair pathway. Structural studies have shown that the
      tyrosine in a highly conserved GQDPY water-activating loop of UDGs blocks the
      entry of thymine or purines into the active site pocket. To further understand
      the role of this tyrosine (Y66 in Escherichia coli UDG), we have overproduced and
      characterized Y66F, Y66H, Y66L and Y66W mutants. The complexes of the wild-type,
      Y66F, Y66H and Y66L UDGs with uracil DNA glycosylase inhibitor (Ugi) (a
      proteinaceous substrate mimic) were stable to 8 M urea. However, some
      dissociation of the complex involving the Y66W UDG occurred at this concentration
      of urea. The catalytic efficiencies (V(max) / K(m)) of the Y66L and Y66F mutants
      were similar to those of the wild-type UDG. However, the Y66W and Y66H mutants
      were approximately 7- and approximately 173-fold compromised, respectively, in
      their activities. Interestingly, the Y66W mutation has resulted in an enzyme
      which is resistant to product inhibition. Preferential utilization of a substrate
      enabling a long range contact between the -5 phosphate (upstream to the scissile
      uracil) and the enzyme, and the results of modeling studies showing that the
      uracil-binding cavity of Y66W is wider than those of the wild type and other
      mutant UDGs, suggest a weaker interaction between uracil and the Y66W mutant.
      Furthermore, the fluorescence spectroscopy of UDGs and their complexes with Ugi,
      in the presence of uracil or its analog, 5-bromouracil, suggests compromised
      binding of uracil in the active site pocket of the Y66W mutant. Lack of
      inhibition of the Y66W UDG by apyrimidinic DNA (AP-DNA) is discussed to highlight
      a potential additional role of Y66 in shielding the toxic effects of AP-DNA, by
      lowering the rate of its release for subsequent recognition by an AP
      endonuclease.

PMID- 14654698
TI  - Repair of a minimal DNA double-strand break by NHEJ requires DNA-PKcs and is
      controlled by the ATM/ATR checkpoint.
AB  - Mammalian cells primarily rejoin DNA double-strand breaks (DSBs) by the non
      homologous end-joining (NHEJ) pathway. The joining of the broken DNA ends appears
      directly without template and accuracy is ensured by the NHEJ factors that are
      under ATM/ATR regulated checkpoint control. In the current study we report the
      engineering of a mono-specific DNA damaging agent. This was used to study the
      molecular requirements for the repair of the least complex DSB in vivo. Single
      chain PvuII restriction enzymes fused to protein delivery sequences transduce
      cells efficiently and induce blunt end DSBs in vivo. We demonstrate that beside
      XRCC4/LigaseIV and KU, the DNA-PK catalytic subunit (DNA-PKcs) is also essential
      for the joining of this low complex DSB in vivo. The appearance of blunt end 3'
      hydroxyl and 5'-phosphate DNA DSBs induces a significantly higher frequency of
      anaphase bridges in cells that do not contain functional DNA-PKcs, suggesting an
      absolute requirement for DNA-PKcs in the control of chromosomal stability during
      end joining. Moreover, these minimal blunt end DSBs are sufficient to induce a
      p53 and ATM/ATR checkpoint function.

PMID- 14654699
TI  - The role of DNA dependent protein kinase in synapsis of DNA ends.
AB  - DNA dependent protein kinase (DNA-PK) plays a central role in the non-homologous
      end-joining pathway of DNA double strand break repair. Its catalytic subunit (DNA
      PK(CS)) functions as a serine/threonine protein kinase. We show that DNA-PK forms
      a stable complex at DNA termini that blocks the action of exonucleases and
      ligases. The DNA termini become accessible after autophosphorylation of DNA
      PK(CS), which we demonstrate to require synapsis of DNA ends. Interestingly, the
      presence of DNA-PK prevents ligation of the two synapsed termini, but allows
      ligation to another DNA molecule. This alteration of the ligation route is
      independent of the type of ligase that we used, indicating that the intrinsic
      architecture of the DNA-PK complex itself is not able to support ligation of the
      synapsed DNA termini. We present a working model in which DNA-PK creates a stable
      molecular bridge between two DNA ends that is remodeled after DNA-PK
      autophosphorylation in such a way that the extreme termini become accessible
      without disrupting synapsis. We infer that joining of synapsed DNA termini would
      require an additional protein factor.

PMID- 14654700
TI  - Discovery and characterization of a thermostable bacteriophage RNA ligase
      homologous to T4 RNA ligase 1.
AB  - Thermophilic viruses represent a novel source of genetic material and enzymes
      with great potential for use in biotechnology. We have isolated a number of
      thermophilic viruses from geothermal areas in Iceland, and by combining high
      throughput genome sequencing and state of the art bioinformatics we have
      identified a number of genes with potential use in biotechnology. We have also
      demonstrated the existence of thermostable counterparts of previously known
      bacteriophage enzymes. Here we describe a thermostable RNA ligase 1 from the
      thermophilic bacteriophage RM378 that infects the thermophilic eubacterium
      Rhodothermus marinus. The RM378 RNA ligase 1 has a temperature optimum of 60-64
      degrees C and it ligates both RNA and single-stranded DNA. Its thermostability
      and ability to work under conditions of high temperature where nucleic acid
      secondary structures are removed makes it an ideal enzyme for RNA ligase-mediated
      rapid amplification of cDNA ends (RLM-RACE), and other RNA and DNA ligation
      applications.

PMID- 14654701
TI  - Residues 190-210 of human topoisomerase I are required for enzyme activity in
      vivo but not in vitro.
AB  - DNA-topoisomerase I (topo I) unwinds the DNA- double helix by cutting one strand
      and allowing rotation of the other. In vitro, this function does not require the
      N-terminal domain of the enzyme, which is believed to regulate cellular
      properties. To assess this role, we studied the cellular distribution and
      mobility of green fluorescent protein-chimera of human topo I lacking either the
      entire N-terminal domain or a portion of it. We find that topo I truncated up to
      position 210 is not stabilized by camptothecin in covalent DNA-complexes inside a
      living cell, whereas in vitro it retains full DNA-relaxation activity, and is
      targeted by camptothecin in the usual manner. This difference is not shared with
      a fragment lacking the N-terminal domain up to position 190, indicating that
      residues 190-210 play a crucial role for the activity of the enzyme in its
      physiological environment, but not in vitro. Since it is impossible to
      discriminate in vivo whether this region is required for topo I to form covalent
      DNA intermediates in the cell, or just for camptothecin to bind and stabilize
      such complexes, we could not explain precisely these cellular observations.
      However, inactivity in vivo of the enzyme lacking this region is indicated by a
      lesser cytotoxicity.

PMID- 14654702
TI  - Transcription factor ZBP-89 is required for STAT1 constitutive expression.
AB  - IFNgamma is a pro-inflammatory cytokine that potentiates p53-independent
      apoptosis in a variety of cell types. STAT1 is the primary mediator of IFNgamma
      action. ZBP-89 is a transcription factor that binds to the G/C-rich elements and
      mediates p53-independent apoptosis. In this study, site-directed mutagenesis
      revealed that a G-rich element from +171 to +179 within the first intron of the
      STAT1 gene is critical for optimal STAT1 promoter activity. Electrophoretic
      mobility shift assays and promoter analysis revealed that ZBP-89 binds directly
      to this STAT1 G-rich element along with Sp1 and Sp3. Reduction of ZBP-89 with
      siRNA attenuated both basal and IFNgamma-induced STAT1 expression and
      subsequently diminished the activation of apoptotic markers, e.g. caspase-3 and
      PARP. Taken together, we conclude that ZBP-89 is required for constitutive STAT1
      expression and in this way contributes to the ability of cells to be activated by
      IFNgamma.

PMID- 14654703
TI  - Gene structure prediction in syntenic DNA segments.
AB  - The accurate prediction of higher eukaryotic gene structures and regulatory
      elements directly from genomic sequences is an important early step in the
      understanding of newly assembled contigs and finished genomes. As more new
      genomes are sequenced, comparative approaches are becoming increasingly practical
      and valuable for predicting genes and regulatory elements. We demonstrate the
      effectiveness of a comparative method called pattern filtering; it utilizes
      synteny between two or more genomic segments for the annotation of genomic
      sequences. Pattern filtering optimally detects the signatures of conserved
      functional elements despite the stochastic noise inherent in evolutionary
      processes, allowing more accurate annotation of gene models. We anticipate that
      pattern filtering will facilitate sequence annotation and the discovery of new
      functional elements by the genetics and genomics communities.

PMID- 14654704
TI  - A statistical sampling algorithm for RNA secondary structure prediction.
AB  - An RNA molecule, particularly a long-chain mRNA, may exist as a population of
      structures. Further more, multiple structures have been demonstrated to play
      important functional roles. Thus, a representation of the ensemble of probable
      structures is of interest. We present a statistical algorithm to sample
      rigorously and exactly from the Boltzmann ensemble of secondary structures. The
      forward step of the algorithm computes the equilibrium partition functions of RNA
      secondary structures with recent thermodynamic parameters. Using conditional
      probabilities computed with the partition functions in a recursive sampling
      process, the backward step of the algorithm quickly generates a statistically
      representative sample of structures. With cubic run time for the forward step,
      quadratic run time in the worst case for the sampling step, and quadratic
      storage, the algorithm is efficient for broad applicability. We demonstrate that,
      by classifying sampled structures, the algorithm enables a statistical
      delineation and representation of the Boltzmann ensemble. Applications of the
      algorithm show that alternative biological structures are revealed through
      sampling. Statistical sampling provides a means to estimate the probability of
      any structural motif, with or without constraints. For example, the algorithm
      enables probability profiling of single-stranded regions in RNA secondary
      structure. Probability profiling for specific loop types is also illustrated. By
      overlaying probability profiles, a mutual accessibility plot can be displayed for
      predicting RNA:RNA interactions. Boltzmann probability-weighted density of states
      and free energy distributions of sampled structures can be readily computed. We
      show that a sample of moderate size from the ensemble of an enormous number of
      possible structures is sufficient to guarantee statistical reproducibility in the
      estimates of typical sampling statistics. Our applications suggest that the
      sampling algorithm may be well suited to prediction of mRNA structure and target
      accessibility. The algorithm is applicable to the rational design of small
      interfering RNAs (siRNAs), antisense oligonucleotides, and trans-cleaving
      ribozymes in gene knock-down studies.

PMID- 14654705
TI  - The poly(A) binding protein Hfq protects RNA from RNase E and exoribonucleolytic
      degradation.
AB  - The Hfq protein, which shares sequence and structural homology with the Sm and
      Lsm proteins, binds to various RNAs, primarily recognizing AU-rich single
      stranded regions. In this paper, we study the ability of the Escherichia coli Hfq
      protein to bind to a polyadenylated fragment of rpsO mRNA. Hfq exhibits a high
      specificity for a 100-nucleotide RNA harboring 18 3'-terminal A-residues.
      Structural analysis of the adenylated RNA-Hfq complex and gel shift assays
      revealed the presence of two Hfq binding sites. Hfq binds primarily to the
      poly(A) tail, and to a lesser extent a U-rich sequence in a single-stranded
      region located between two hairpin structures. The oligo(A) tail and the
      interhelical region are sensitive to 3'-5' exoribonucleases and RNase E
      hydrolysis, respectively, in vivo. In vitro assays demonstrate that Hfq protects
      poly(A) tails from exonucleolytic degradation by both PNPase and RNase II. In
      addition, RNase E processing, which occurred close to the U-rich sequence, is
      impaired by the presence of Hfq. These data suggest that Hfq modulates the
      sensitivity of RNA to ribonucleases in the cell.

PMID- 14654706
TI  - Effect of G-1 on histidine tRNA microhelix conformation.
AB  - Histidine tRNAs (tRNA(His)) are unique in that they possess an extra 5'-base (G
      1) not found in other tRNAs. Deletion of G-1 results in at least a 250-fold
      reduction in the rate of histidine charging in vitro. To better understand the
      role of the G-1 nucleotide in defining the structure of tRNA(His), and to
      correlate structure with cognate amino acid charging, NMR and molecular dynamics
      (MD) studies were performed on the wild-type and a DeltaG-1 mutant Escherichia
      coli histidine tRNA acceptor stem microhelix. Using NMR-derived distance
      restraints, global structural characteristics are described and interpreted to
      rationalize experimental observations with respect to aminoacylation activity.
      The quality of the NMR-derived solution conformations of the wild-type and DeltaG
      1 histidine microhelices (micro helix(His)) is assessed using a variety of MD
      based computational protocols. Most of the duplex regions of the acceptor stem
      and the UUCG tetraloop are well defined and effectively superimposable for the
      wild-type and DeltaG-1 mutant microhelix(His). Differences, however, are observed
      at the end of the helix and in the single-stranded CCCA-3' tail. The wild-type
      microhelix(His) structure is more well defined than the mutant and folds into a
      'stacked fold-back' conformation. In contrast, we observe fraying of the first
      two base pairs and looping back of the single-stranded region in the DeltaG-1
      mutant resulting in a much less well defined conformation. Thus the role of the
      extra G-1 base of the unique G-1:C73 base pair in tRNA(His) may be to prevent end
      fraying and stabilize the stacked fold-back conformation of the CCCA-3' region.

PMID- 14654707
TI  - A PCR primer bank for quantitative gene expression analysis.
AB  - Although gene expression profiling by microarray analysis is a useful tool for
      assessing global levels of transcriptional activity, variability associated with
      the data sets usually requires that observed differences be validated by some
      other method, such as real-time quantitative polymerase chain reaction (real-time
      PCR). However, non-specific amplification of non-target genes is frequently
      observed in the latter, confounding the analysis in approximately 40% of real
      time PCR attempts when primer-specific labels are not used. Here we present an
      experimentally validated algorithm for the identification of transcript-specific
      PCR primers on a genomic scale that can be applied to real-time PCR with sequence
      independent detection methods. An online database, PrimerBank, has been created
      for researchers to retrieve primer information for their genes of interest.
      PrimerBank currently contains 147 404 primers encompassing most known human and
      mouse genes. The primer design algorithm has been tested by conventional and real
      time PCR for a subset of 112 primer pairs with a success rate of 98.2%.

PMID- 14654708
TI  - A novel MALDI-TOF based methodology for genotyping single nucleotide
      polymorphisms.
AB  - A new MALDI-TOF based detection assay was developed for analysis of single
      nucleotide polymorphisms (SNPs). It is a significant modification on the classic
      three-step minisequencing method, which includes a polymerase chain reaction
      (PCR), removal of excess nucleotides and primers, followed by primer extension in
      the presence of dideoxynucleotides using modified thermostable DNA polymerase.
      The key feature of this novel assay is reliance upon deoxynucleotide mixes,
      lacking one of the nucleotides at the polymorphic position. During primer
      extension in the presence of depleted nucleotide mixes, standard thermostable DNA
      polymerases dissociate from the template at positions requiring a depleted
      nucleotide; this principal was harnessed to create a genotyping assay. The assay
      design requires a primer- extension primer having its 3'-end one nucleotide
      upstream from the interrogated site. The assay further utilizes the same DNA
      polymerase in both PCR and the primer extension step. This not only simplifies
      the assay but also greatly reduces the cost per genotype compared to
      minisequencing methodology. We demonstrate accurate genotyping using this
      methodology for two SNPs run in both singleplex and duplex reactions. We term
      this assay nucleotide depletion genotyping (NUDGE). Nucleotide depletion
      genotyping could be extended to other genotyping assays based on primer extension
      such as detection by gel or capillary electrophoresis.

PMID- 14654709
TI  - Tumor marker workshops.
AB  - Since 1996, the nine ISOBM Workshops have so far characterized more than 300
      monoclonal antibodies to a variety of tumor markers that include CA125, AFP, PSA,
      MUC1, Cytokeratins, Sialyl Le(a), hCG, CEA, ALP, and more recently SCC, and S100.
      Besides the basic characterization of antibodies and their epitope
      configurations, several workshops have also addressed specific problems
      associated with multiple antigen variants. These workshops have been able to make
      significant advances well beyond those possible through any normal collaboration
      study. The data and impact of these workshops with their summary reports are
      reviewed.

PMID- 14654710
TI  - Serum CA 125 levels in patients with chronic heart failure and accompanying
      pleural fluid.
AB  - Malignant and nonmalignant serosal fluids have been found to be associated with
      high serum levels of CA 125, suggesting that the presence of fluid in the serosal
      cavities may stimulate its release. In this study, we investigated the
      relationship between serum CA 125 levels and the presence of pleural fluid in
      patients with chronic heart failure (CHF). We performed a clinical study in 36
      patients with CHF with and without pleural fluid. Patients with CHF were divided
      into two groups based on the presence of fluid in the pleural cavity. Group 1
      included 18 CHF patients (6 females, 12 males) with pleural fluid. Group 2
      consisted of 18 CHF patients (7 females, 11 males) without pleural fluid. The
      control group consisted of 30 healthy volunteers (12 females, 18 males). The
      serum CA 125 level was determined in all groups. Serum CA 125 levels were found
      to be 100.0 +/- 129.4 U/ml in CHF patients with pleural fluids, whereas they were
      36.5 +/- 35.2 U/ml in CHF patients without pleural fluid and 8.9 +/- 6.1 U/ml in
      the control group. Significantly high serum CA 125 levels were found in CHF
      patients with pleural fluids (p < 0.05) when compared with both CHF patients
      without pleural fluid and the control group. There was also a statistically
      significant difference in CA 125 levels between patients without pleural fluid
      and the control group (p < 0.05). We concluded that serum CA 125 levels should be
      interpreted with caution in patients with CHF in the presence of pleural fluid.
      Invasive procedures to define the etiology of elevated serum CA 125 levels may be
      unnecessary in this patient group.

PMID- 14654711
TI  - Establishment and characterization of clonal cell lines derived from a
      fibrosarcoma of the H2-K/V-JUN transgenic mouse. A model of H2-K/V-JUN mediated
      tumorigenesis.
AB  - We used fibrosarcoma from an H2-K/V-JUN transgenic mouse to derive a series of
      three immortal cell lines (JUN-1, -2, and -3). The cell lines exhibit strikingly
      different behavior regarding phenotype transformation. Features examined include
      contact inhibition and density limitation of growth, proliferation, invasiveness,
      motility, and organization of the microfilament system. Overall, JUN-2 and JUN-3
      represent extreme phenotypes, with JUN-2 having a phenotype indicative of low
      level cellular transformation and JUN-3 meeting all the criteria of the
      transformed phenotype. JUN-1 cells can also be regarded as transformed, but to a
      lesser extent than JUN-3. Their phenotype is in the majority of characteristics
      intermediary between JUN-2 and JUN-3. The transformation status is inversely
      related to the expression of the V-JUN transgene, which is the highest in JUN-2,
      lower in JUN-1 and very low in JUN-3. This might be related to the MHC class I
      promoter driving its expression and to the general observation of repression of
      MHC class I genes coupled with cellular transformation. Based on this premise, we
      present a model of H2-K/V-JUN-mediated tumorigenesis, in which v-jun-conditioned
      transformation represents merely an initial phase of tumorigenesis. Later during
      tumor progression, additional oncogenes are activated and/or tumor suppressor
      genes inactivated, leading on the one hand to further exacerbation of the
      transformed phenotype, and on the other hand to the repression of the H2-K/V-JUN
      transgene (fixed in JUN-3). We believe that the system of JUN cell lines can be
      valuable for further molecular analysis of transformation-related traits.

PMID- 14654712
TI  - Relationship of p53 with other oncogenes, cytokines and systemic lupus
      erythematosus activity.
AB  - INTRODUCTION: Defects in the regulation of apoptosis of autoreactive lymphocytes
      are involved in the pathogenesis of systemic lupus erythematosus (SLE). The
      apoptotic process relies on adequate functioning of numerous molecules, including
      oncogenes and diverse cytokines. p53 has been implicated in the control of the
      cell cycle through the stimulation of apoptosis of these autoreactive cells.
      OBJECTIVE: To study the role of the p53 pathway on the regulation of apoptosis in
      SLE patients and analyze the relationship of the p53 oncoprotein with disease
      activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10,
      and tumor necrosis factor-alpha, TNF-alpha), implicated in the apoptotic process
      and the pathogenesis of SLE. PATIENTS AND METHODS: p53 and bcl-2 antigen
      expression were determined in lyzed lymphocytes from 74 patients with SLE and 30
      healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF
      alpha were studied by enzyme-linked immunonosorbent assay. RESULTS: SLE patients
      had higher levels of p53 protein (0.16 +/- 0.33 ng/dl) than controls (0.014 +/-
      0.02 ng/dl; p = 0.006). Patients with active SLE had higher levels of p53 (0.31
      +/- 0.48 ng/dl) than those with inactive disease (0.08 +/- 0.17 ng/dl; p = 0.003)
      who in turn had higher levels than controls (0.01 +/- 0.02 ng/dl; p = 0.035). A
      significant correlation was found between p53 levels and the SLE disease activity
      index (R = +0.24/ p = 0.04), anti-DNA antibodies (R = +0.23/p = 0.048) and IL-10
      levels (R = +0.4/p = 0.004). No correlation was found between p53 levels and bcl
      2, sFas or TNF-alpha levels. CONCLUSIONS: The p53 oncoprotein may play a role in
      the pathogenesis and activity of SLE. IL-10 may influence SLE activity by
      inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells.

PMID- 14654713
TI  - Identification of genes associated with the invasive status of human mammary
      carcinoma cell lines by transcriptional profiling.
AB  - We derived the transcriptional profiles of four invasive and four noninvasive
      mammary carcinoma cell lines by Affymetrix GeneChip((R)) Technology with the
      profile of human mammary epithelial cells as a reference. We focused on the
      identification of genes which are upregulated in the invasive cell lines based on
      the following threshold levels: -fold change of 2 or higher in at least three or
      more cell lines. According to the scoring criteria as described above, we
      identified 18 transmembrane receptors, 18 secreted proteins and 5 kinases.
      Several of the genes described have already been put into context with respect to
      invasion of mammary carcinoma. We therefore focused on deregulated genes for
      which such an association has not been described before: transmembrane receptor
      tyrosine kinase DDR2, transmembrane receptors PMP22 and EMP3 and cell adhesion
      molecule N-cadherin. Making use of real-time PCR, consistently increased steady
      state levels of mRNAs for these genes were found in an extended panel of invasive
      and noninvasive mammary cancer cell lines.

PMID- 14654714
TI  - Lactate dehydrogenase isoenzymes 1 and 5: differential expression by neoplastic
      and stromal cells in non-small cell lung cancer and other epithelial malignant
      tumors.
AB  - BACKGROUND/AIMS: Lactate dehydrogenase-5 (LDH-5), an isoenzyme composed of 4 M
      polypeptide chains, catalyzes the conversion of pyruvate to lactate with an
      unparalleled efficiency (anaerobic oxidation), but this function of LDH gradually
      fades away as the number of H over M chains increases. Thus, LDH-1, another
      component isoenzyme made up of 4 H-polypeptide chains, favors aerobic oxidation
      of pyruvate by pyruvate dehydrogenase. METHODS: Using immunohistochemistry in
      this study, we explored the expression of LDH-1 and LDH-5 in a variety of normal
      and malignant tissues, including lung, breast, endometrium, urinary bladder and
      large intestine. RESULTS: LDH-1 was consistently expressed in all living cells,
      normal and malignant, epithelial and stromal, including endothelium and
      lymphocytes. In contrast, LDH-5 was expressed preferentially in tumor cells,
      while normal tissues were devoid of LDH-5 or expressed it only faintly, and the
      cellular population of the tumor-supporting stroma showed LDH-5 activity in a
      small percentage of cases. Interestingly, LDH-5-positive stromal cells were
      associated with hypoxia-inducible factor-1alpha overexpression. CONCLUSION: It is
      concluded that normal tissues utilize aerobic oxidation as a means of energy
      production, while tumor cells are turned to anaerobic glycolysis, a phenomenon
      which is rarely followed by the mesenchymal cells of the tumor-supporting stroma.

PMID- 14654715
TI  - Expression of adipocyte-derived leucine aminopeptidase in endometrial cancer.
      Association with tumor grade and CA-125.
AB  - Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel zinc-metallopeptidase
      involved in angiotensin II (AngII) metabolism, cell migration and antigen
      presentation. These functions are implicated in the progression of cancer,
      whereas A-LAP expression and involvement have not been studied in any type of
      cancer. We investigated the expression of A-LAP in endometrial cancer as well as
      its association with angiogenesis and clinicopathological features.
      Immunohistochemical staining of 58 endometrial endometrioid adenocarcinoma
      specimens revealed that 37 were A-LAP immunoreactive. We also found that A-LAP
      staining correlated with histological tumor grade in a significant and reverse
      manner. In addition, serum CA-125 levels in patients with A-LAP positive cancers
      were significantly higher. However, contrary to our hypothesis that A-LAP
      suppresses angiogenic activity via AngII metabolism, A-LAP expression was not
      associated with the microvessel count determined by CD34 immunostaining. Our
      results suggest that A-LAP is involved in endometrial cancer cell growth and
      differentiation. However, further studies, especially of the biological roles of
      A-LAP, are required to confirm this notion.

PMID- 14654716
TI  - Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small
      cell lung cancer as an aid in histological diagnosis and prognosis. Comparison
      with the main clinical and pathological prognostic factors.
AB  - CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients
      with non-small cell lung cancer and compared with clinical parameters (age, sex,
      Karnofsky Index, symptoms and smoking status), histopathological parameters
      (stage, histology, tumor size and nodal involvement), biological parameters (LDH
      and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor
      marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE:
      22%. One of the tumor markers was abnormally high in 87% of the patients with
      locoregional disease and in 100% of the patients with metastases. Except for NSE,
      all tumor markers showed a clear relationship with tumor stage and histology and
      therefore enabled a better histological diagnosis. Abnormal CEA serum levels were
      mainly found in adenocarcinomas, CA 125 in large-cell lung cancers (LCLC) and
      adenocarcinomas and SCC in squamous tumors. Eighty-five percent of the patients
      with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or
      CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%,
      respectively.

PMID- 14654717
TI  - Tissue-specific utilization of menaquinone-4 results in the prevention of
      arterial calcification in warfarin-treated rats.
AB  - The effects of vitamin K (phylloquinone: K1 and menaquinone-4: MK-4) on vascular
      calcification and their utilization in the arterial vessel wall were compared in
      the warfarin-treated rat model for arterial calcification. Warfarin-treated rats
      were fed diets containing K1, MK-4, or both. Both K1 and MK-4 are cofactors for
      the endoplasmic reticulum enzyme gamma-glutamyl carboxylase but have a
      structurally different aliphatic side chain. Despite their similar in vitro
      cofactor activity we show that MK-4 and not K1 inhibits warfarin-induced arterial
      calcification. The total hepatic K1 accumulation was threefold higher than that
      of MK-4, whereas aortic MK-4 was three times that of K1. The utilization of K1
      and MK-4 in various tissues was estimated by calculating the ratios between
      accumulated quinone and epoxide species. K1 and MK-4 were both equally utilized
      in the liver, but the aorta showed a more efficient utilization of MK-4.
      Therefore, the observed differences between K1 and MK-4 with respect to
      inhibition of arterial calcification may be explained by both differences in
      their tissue bioavailability and cofactor utilization in the
      reductase/carboxylase reaction. An alternative explanation may come from an as
      yet hypothetical function of the geranylgeranyl side chain of MK-4, which is a
      structural analogue of geranylgeranyl pyrophosphate and could interfere with a
      critical step in the mevalonate pathway.

PMID- 14654718
TI  - Effect of different growth hormone dosages on the growth velocity in children
      born small for gestational age.
AB  - To assess whether short-term growth hormone (GH) treatment can improve the linear
      growth in children who were born small for gestational age (SGA), we started a
      randomized multicenter trial in 26 age- and sex-matched prepubertal children born
      SGA. During the 1st year of GH therapy, all children received GH 0.23 mg/kg/week,
      then during the 2nd year, 13 children received the same dose (group A), and in
      the other 13 children, the dose of GH was doubled, i.e., 0.46 mg/kg/week (group
      B). During the 1st year of therapy, the growth velocity significantly (p<0.0001)
      increased in all patients. During the 2nd year, group A showed a significant
      decrease of the growth velocity (p<0.015), whereas group B maintained the growth
      rate. The height in group A children significantly increased during the 1st and
      the 2nd year of GH therapy (p<0.000002 and p<0.000001, respectively), reaching
      the normal range in 8 out of 13 children at the end of 2 years of GH therapy. The
      height in group B children significantly increased during the 1st and the 2nd
      year of GH therapy (p<0.000001 and p<0.000001, respectively), reaching the normal
      range in all 11 children who completed the GH therapy. The height gain was
      similar in groups A and B treated with the same GH dosage during the 1st year of
      therapy. A greater increase in height gain was found in children of group B
      treated with the higher GH dosage during the 2nd year of therapy as compared with
      group A (p<0.02). Significant increases in insulin-like growth factor I
      (p<0.0001), acid-labile subunit (p<0.0002), and bone/chronological age ratio
      (p<0.0001) were found after the 1st year of GH therapy, but no significant
      changes were observed during the 2nd year, independently of the GH dose. In
      conclusion, the height velocity of children born SGA significantly increases
      during the 1st year of GH therapy, diminishes, but can decrease during the 2nd
      year, if the GH dosage is not raised.

PMID- 14654719
TI  - What's it all about: variation and aging.

PMID- 14654720
TI  - Intraindividual variability, change, and aging: conceptual and analytical issues.
AB  - BACKGROUND: Developmental researchers use a variety of research designs to
      examine aging-related changes. Most longitudinal studies of aging are based on
      research designs that feature successive, widely spaced, assessments to estimate
      changes in cognitive performance. Such designs assume that short-term variations
      in cognitive performance are small relative to long-term changes or have modeled
      such phenomena as nuisance parameters. OBJECTIVE: There is now sufficient
      empirical evidence to establish intraindividual cognitive variability as a
      systematic source of individual differences and of important predictive value for
      aging-relevant outcomes. METHODS: After an overview of types of change, potential
      underlying processes, and adequate analytic designs, we discuss consequences for
      lifespan aging research. RESULTS: We emphasize that interpretations of both cross
      sectional and longitudinal results need to consider and specify theoretical
      assumptions about short-term and long-term changes. CONCLUSIONS: Above and beyond
      the analysis of long-term mean changes, short- term changes are an important
      aspect of aging-related change, and their analysis may help to explain
      psychological processes of adaptation.

PMID- 14654721
TI  - Static and dynamic longitudinal structural analyses of cognitive changes in old
      age.
AB  - BACKGROUND: Among the main data-analytical advances of recent decades are Latent
      Growth Models (LGM) and Multilevel Models (MLM) for the analysis of longitudinal
      data. OBJECTIVE: We discuss the relative advantages and disadvantages of the two
      analytical methods and offer some practical guidelines concerning the choice
      between LGM and MLM based on (a). completeness and balance of the data, (b).
      theoretical functional form of change examined, (c). examination of the error
      structure, (d). theoretical relations among differential level effects and
      differential change effects, and (e). role of time-invariant covariates. METHODS:
      To discuss LGM and MLM, we provide illustrations from applications to the Berlin
      Aging Study (BASE) and the Swiss Interdisciplinary Longitudinal Study on the
      Oldest Old (SWILSO-O). RESULTS: As predicted by two-component theories of
      lifespan cognition, performance on a vocabulary test (indicator of broad
      crystallized intelligence) did not decline over time, while scores on a digit
      letter test (indicator of broad fluid intelligence) decreased over 6 years.
      Differential level effects were obtained on both variables, while average and
      differential change effects were obtained only for the digit letter test. In a
      second set of analyses, we tested the error-free effect that a broad fluid
      intelligence indicator exerted on the latent yearly change in a broad
      crystallized intelligence indicator, and vice versa. In both data sets we
      obtained strong evidence for a more reliable effect of the fluid indicator on the
      change in the crystallized indicator. This evidence provided support for the
      dedifferentiation hypothesis of cognitive abilities in very old age. CONCLUSIONS:
      New insights into cognitive aging phenomena can be gained with proper
      applications of LGM and MLM. We posit that the choice between LGM and MLM and
      their specification rests on theoretical and empirical motives to be defined a
      priori.

PMID- 14654722
TI  - Short-term versus long-term longitudinal changes in processing speed.
AB  - BACKGROUND: Previous longitudinal studies of cognitive aging have focused on long
      term performance changes. A recent surge of research has demonstrated that there
      are reliable interindividual differences in short-term cognitive performance
      changes. OBJECTIVE: The present study links these two pathways of cognitive aging
      research by examining the association between short-term (learning, practice)
      versus long-term (development) changes in processing speed. METHODS: Data from
      963 elderly participants come from the Longitudinal Aging Study Amsterdam (LASA).
      RESULTS: Nested latent growth curve analyses show that the amount of learning or
      practice in processing speed at first measurement occasion is positively related
      (r = 0.72) to individual differences in development of processing speed across 6
      years. CONCLUSIONS: Short-term learning or practice gains in processing speed are
      positively associated with long-term developmental changes in processing speed in
      the elderly.

PMID- 14654723
TI  - Age differences in the heritability of mean and intraindividual variation of
      psychological distress.
AB  - BACKGROUND: An important question in the study of intraindividual variability is
      whether the same explanatory mechanisms govern between person variation and
      within person variation. OBJECTIVE: This paper investigates genetic and
      environmental influences on affect across varying time frames and genetic and
      environmental influences on within person variation in affect. METHODS: Twin
      participants aged 25-74 years provided information on their affective experiences
      over monthly, weekly, and daily recall periods. Questionnaires and daily
      telephone interviews were used to assess frequency of negative emotions. RESULTS:
      Monthly, weekly, and daily reports of negative affect all showed modest genetic
      influence. Monthly and daily measures also demonstrated modest shared
      environmental influence. Sibling resemblance in within-person variation in affect
      was accounted for entirely by shared environment. Tests for age differences in
      magnitude of genetic and environmental effects revealed that genetic influences
      on monthly reports of affect were greater among older adults, but genetic
      influences on daily affective experiences were lower among older adults.
      CONCLUSIONS: Lowered heritability in daily affect among older adults contradicts
      standard behavior genetic expectations, and is consistent with the proposition
      that older adults gain skills in emotion regulation.

PMID- 14654724
TI  - Aging and attenuated processing robustness. Evidence from cognitive and
      sensorimotor functioning.
AB  - BACKGROUND: Within-person, across-time variations in processes and performance
      are intrinsic to all aspects of human functioning. OBJECTIVE: This article starts
      with a brief taxonomy of intraindividual dynamics. There are adaptive as well as
      non-adaptive types of intraindividual variations that unfold with different
      degrees of reversibility on different time scales and involve either single, or
      systems of, functions. METHODS: Empirical findings regarding aging and a specific
      type of intraindividual variation, namely attenuated processing robustness, are
      then presented with respect to cognitive and sensorimotor functioning. RESULTS:
      In both domains of functioning, old adults exhibit less robust functioning with a
      greater amount of week-to-week, day-to-day, or trial-by-trial fluctuations in
      their cognitive, walking, and postural control performances. CONCLUSION:
      Currently, the causes for the attenuation of processing robustness in cognitive
      and sensorimotor functioning are not well understood. Neurocomputational models
      are useful tools for exploring the tripartite relationships between the aging of
      neural information-processing fidelity, and cognitive, and sensorimotor
      processes.

PMID- 14654725
TI  - Gender differences in level and change in cognitive functioning. Results from the
      Longitudinal Aging Study Amsterdam.
AB  - BACKGROUND: Gender differences in level of cognitive functioning are frequently
      observed, but little is known about gender differences in rate of decline of
      cognitive functioning. OBJECTIVE: The present study aims to describe variability
      between and within men and women specified for four different cognitive abilities
      at baseline, and variability in change in these abilities among men and women
      over 6 years. METHODS: We started with a study sample of 1132 men and 1175 women,
      with a measurement interval of 3 years. At wave 3 of the study, 1552 of the
      respondents from wave 1 were still present. Differences in level and rate of
      change were estimated with latent change models. RESULTS: Women have higher
      levels of memory functioning then men, but no gender differences were observed
      for speed or non-verbal reasoning changes. CONCLUSION: In spite of evidence for a
      stronger age-related atrophy of the brain structure of men, no gender differences
      in decline of cognitive functions could be observed.

PMID- 14654726
TI  - MMSE cross-domain variability predicts cognitive decline in centenarians.
AB  - BACKGROUND: Early detection of dementia is one of the key issues in cognitive
      gerontology. However, so far the detection of early stages in cognitive decline
      has been rather unreliable. One central limitation of current assessment
      strategies is that they rely on information about a person's level of performance
      obtained from a single assessment. OBJECTIVE: In the first part of the present
      paper, we propose three strategies for overcoming this limitation by using
      information from several measurement occasions to improve diagnostic reliability.
      METHODS: In the second part, we present one exemplary empirical analysis of one
      of these approaches reporting data from the Heidelberg Centenarian Study.
      RESULTS: In this sample of very old individuals tested at baseline and at a
      follow-up 18 months later, the intra-individual cross-domain variability across
      MMSE subscales [1]at baseline predicted cognitive decline (i.e. change in an
      external cognitive functioning rating from baseline to follow-up) much better
      than baseline mean MMSE scores. CONCLUSIONS: In conclusion, we discuss the
      advantage of performance variability as a predictor for cognitive decline.

PMID- 14654727
TI  - Intraindividual variability and short-term change. Commentary.
AB  - BACKGROUND: Interest in the study of intraindividual variability is growing
      rapidly. OBJECTIVE: The present collection of papers deals with both longer-term,
      growth and change and shorter-term intraindividual variability. METHODS: The
      papers emphasize primarily the former within the context of analyzing large,
      longitudinal data sets. Also discussed are some key methodological matters.
      RESULTS: Criteria to help with choosing methods and modeling with missing data
      are included. CONCLUSIONS: A promising direction is toward developing a more
      systematic and intensive conception of the meaning and significance of the wide
      variety of manifestations of intraindividual variability and integrating them
      into theories of aging.

PMID- 14654728
TI  - Von Hippel-Lindau tumor suppressor protein and hypoxia-inducible factor in kidney
      cancer.
AB  - The development of hereditary von Hippel-Lindau (VHL) disease and the majority of
      sporadic kidney cancers are due to the functional inactivation of the VHL gene.
      The product of the VHL gene, pVHL, in association with elongins B and C, cullin
      2, and Rbx1 form an E3 ubiquitin-ligase complex VEC that targets the alpha
      subunits of hypoxia-inducible factor (HIF) for ubiquitination. Ubiquitin-tagged
      HIF-alpha proteins are subsequently degraded by the common 26S proteasome. pVHL
      functions as the substrate-docking interface that specifically recognizes prolyl
      hydroxylated HIF-alpha. This hydroxylation occurs only in the presence of oxygen
      or normoxia. Thus, under hypoxia, HIF-alpha subunits are no longer subjected to
      degradation and are thereby able to dimerize with the common and constitutively
      stable beta subunits. The heterodimeric HIFs upregulate a myriad of hypoxia
      inducible genes, triggering our physiologic response to hypoxia. Inappropriate
      accumulations of HIF-alpha in VHL disease are believed to contribute to the
      pathogenesis via the upregulation of several of these HIF target genes. Our
      current molecular understanding of the roles of HIF and pVHL in the development
      of VHL-associated clear-cell renal cell carcinoma (CC-RCC) is the focus of this
      review.

PMID- 14654729
TI  - Albumin stimulates the accumulation of extracellular matrix in renal tubular
      epithelial cells.
AB  - The accumulation of a large amount of plasma proteins in the urine, previously
      regarded as a marker of glomerular damage, is now recognized as a mediator of
      tubulointerstitial damage. Using an in vitro approach, several key extracellular
      matrix (ECM) proteins were analyzed after treatment of primary human renal
      proximal tubular epithelial cells with fatty acid free human albumin. We
      demonstrate that human albumin stimulates the accumulation of ECM proteins by
      proximal tubular epithelial cells through a post-transcriptional mechanism.
      Albumin induced a significant increase in tissue inhibitor of metalloproteinases
      (TIMP)-1 and TIMP-2. Taken together, our data suggest that ECM protein
      accumulation in response to albumin resulted partly from inhibition of ECM
      degradation. Addition of transforming growth factor beta (TGF-beta)-specific
      neutralizing antibody failed to alter ECM protein levels after albumin treatment,
      indicating that the albumin-induced increase in ECM is TGF-beta independent. In
      conclusion, we have shown that exposure of cultured human proximal tubular cell
      to albumin leads to the TGF-beta-independent accumulation of ECM proteins,
      suggesting that albumin may be a contributing factor to the progression of kidney
      fibrosis in proteinuric states.

PMID- 14654730
TI  - Cross-cultural perspectives on the concept of retirement: an analytic
      redefinition.
AB  - A cross-cultural valid analytic definition of retirement remains elusive in
      gerontology despite a long tradition of research on the topic. Inadequate
      attention has been paid to consistently defining the key concepts used to examine
      retirement and to specifying its occurrence in non-Western, non-industrial
      societies. This paper critically reviews basic cultural tenets in the notion of
      retirement, and proposes a more comparatively valid definition. It then proposes
      a three part comparative categorization by exploring retirement in contemporary
      Western nations and comparing it with retirement-like practices from a range of
      non-Western cultures including Thai, Chinese, Ladak, Fulani, Lusi and Aymara.

PMID- 14654731
TI  - Aging service need and use among chinese american seniors: intragroup variations.
AB  - Existing literature on aging service use by Asian/Chinese American seniors mainly
      focuses on documenting and explaining low service use in the Asian/Chinese senior
      population. However, service use is not uniformly low, and variations in need and
      use do occur within the Asian/Chinese senior population. Little research focuses
      on these service need and use variations. This paper focuses on those variations
      within one group, Chinese American seniors. Through a community-based case study,
      we found, first, that Chinese American seniors are internally diversified, and
      consist of several subgroups, which can be identified largely through immigration
      timing and status, work history, current living situations, and language and
      driving ability. Second, each subgroup has particular service need and use
      patterns. Third, service need and use variations are related to the
      characteristics that define the subgroups, to perceptions of service need,
      availability, accessibility and to service source preference. The findings from
      this study suggest that research in general about service need and use by
      minority seniors may be helped through more detailed analyses by sub-population,
      and through the use of perceptions of service availability and accessibility and
      service source preference.

PMID- 14654732
TI  - "Die lewe vat ek net soos ek dit kry." Life stories and remembrance of older
      coloured people on farms in the western cape province.
AB  - The article is an exploration of the past, present and future of older farm
      workers on wine farms in the Western Cape Province in South Africa. The author
      shows by means of ethnographic material that life stories of older people reveal
      how they have overcome poverty, exploitation and violence. The aim of the paper
      is to answer the question of the meaning of those life stories for older people
      and others. The author shows that the paternalistic system on the wine farms has
      positive and negative aspects. It is also argued that the gap between older
      people and younger generations is more than a 'generation gap' and signifies the
      profound changes in identity of South African citizens. The present 'violence
      complex' on farms is situated within the workers' families. The author argues
      that the nature of the relationships between farm owners and older farm workers
      safeguard older people against violence.

PMID- 14654733
TI  - Costs of implementing recommendations on hypertension management given in recent
      guidelines.

PMID- 14654734
TI  - Extracellular matrix biology: a new frontier in linking the pathology and therapy
      of hypertension?
AB  - The extracellular matrix (ECM) is a vital component of connective tissue, and
      collagen is a major constituent. There is growing evidence that changes in the
      composition of the cardiac and vascular matrix occurs during hypertension.
      Clinically, these effects are manifested as left ventricular hypertrophy and a
      reduction in arterial compliance and luminal diameter, which results in end organ
      ischaemia. The matrix metalloproteinases and their inhibitors have a central role
      in the regulation of the composition of the ECM. In this review, we discuss the
      mediators that affect the structure of the ECM in hypertension using results from
      animal and human studies.

PMID- 14654735
TI  - Renin-angiotensin-aldosterone system polymorphisms and essential hypertension:
      where are we?

PMID- 14654736
TI  - Self-measurement of blood pressure in the office and at home.

PMID- 14654737
TI  - Oral contraceptives and endothelial function: harm or benefit?

PMID- 14654738
TI  - Mediterranean diet, cocoa and cardiovascular disease: a sweeter life, a longer
      life, or both?

PMID- 14654739
TI  - Activated oxygen metabolites: do they really play a role in angiotensin II
      regulated vascular tone?

PMID- 14654740
TI  - Involvement of neuroadrenergic factors in hypertensive vascular remodelling: myth
      or reality?

PMID- 14654741
TI  - Is nitrotyrosine a footprint of nitric oxide release?

PMID- 14654742
TI  - The angiotensin-endothelin relationship: does it play a role in cardiovascular
      and renal pathophysiology?

PMID- 14654743
TI  - Hypertension in very old people.

PMID- 14654744
TI  - Systolic blood pressure variability as a risk factor for stroke and
      cardiovascular mortality in the elderly hypertensive population.
AB  - OBJECTIVE: To investigate whether baseline systolic blood pressure variability
      was a risk factor for stroke, cardiovascular mortality or cardiac events during
      the Syst-Eur trial. DESIGN: The Syst-Eur study was a randomized, double-blind,
      placebo-controlled trial, powered to detect differences in stroke rate between
      participants on active antihypertensive treatment and placebo. Systolic blood
      pressure variability measurements were made on 744 participants at the start of
      the trial. Systolic blood pressure variability was calculated over three time
      frames: 24 h, daytime and night-time. The placebo and active treatment subgroups
      were analysed separately using an intention-to-treat principle, adjusting for
      confounding factors using a multiple Cox regression model. PARTICIPANTS: An
      elderly hypertensive European population. MAIN OUTCOME MEASURES: Stroke, cardiac
      events (fatal and non-fatal heart failure, fatal and non-fatal myocardial
      infarction and sudden death) and cardiovascular mortality (death attributed to
      stroke, heart failure, myocardial infarction, sudden death, pulmonary embolus,
      peripheral vascular disease and aortic dissection). RESULTS: The risk of stroke
      increased by 80% (95% confidence interval: 17-176%) for every 5 mmHg increase in
      night-time systolic blood pressure variability in the placebo group. Risk of
      cardiovascular mortality and cardiac events was not significantly altered.
      Daytime variability readings did not predict outcome. Antihypertensive treatment
      did not affect systolic blood pressure variability over the median 4.4-year
      follow-up. CONCLUSION: In the placebo group, but not the active treatment group,
      increased night-time systolic blood pressure variability on admission to the Syst
      Eur trial was an independent risk factor for stroke during the trial.

PMID- 14654745
TI  - Home or self blood pressure measurement? What is the correct term?
AB  - OBJECTIVE: Blood pressure measurements taken by patients at home (HBP) are
      usually referred to as 'self' or 'home' measurements. To demonstrate the most
      appropriate term we compared self-home measurements (S-HBP), with home
      measurements taken by relatives (R-HBP), clinic measurements taken by physicians
      (P-CBP) and self-measurements in the clinic (S-CBP). PATIENTS AND METHODS: Thirty
      treated hypertensives were randomized to an initial clinic BP (CBP) monitoring
      period (week 1, P-CBP followed by S-CBP measurements, or the opposite; 1 visit
      each), then to a HBP monitoring period (weeks 2-3, S-HBP followed by R-HBP or the
      opposite; 3 workdays each), and finally to a second CBP monitoring period (week
      4, S-CBP followed by P-CBP, or the opposite). Triplicate morning trough
      measurements were taken per occasion using the same fully automated device.
      RESULTS: There was no difference between S-CBP and P-CBP (mean difference -1.9 +/
      6.1 mmHg, 95% confidence interval (CI) -4.2, 0.4/-1.6 +/- 4.7, 95% CI -3.3, 0.2,
      systolic/diastolic), or between S-HBP and R-HBP (-0.9 +/- 6.9, 95% CI -3.5, 1.8/
      0.4 +/- 4.3, 95% CI -2.0, 1.2). S-CBP was higher than S-HBP (mean difference 9.3
      +/- 9.0/4.9 +/- 5.4 mmHg, systolic/diastolic, P < 0.001) and R-HBP (8.4 +/-
      9.1/4.5 +/- 5.0, P < 0.001). P-CBP was also higher than S-HBP (11.2 +/- 11.9/6.5
      +/- 6.8, P < 0.001) and R-HBP (10.3 +/- 11.2/6.1 +/- 6.5, P < 0.001).
      CONCLUSIONS: Self-measurements provide similar BP levels to measurements taken by
      relatives or physicians, provided that measurements are taken in the same
      setting. 'Self-BP' is a misnomer because self-measurement has no impact on the
      difference between home and clinic BP. Given that this difference can be
      exclusively attributed to the effect of the different setting, the term 'home BP'
      represents a more appropriate term.

PMID- 14654746
TI  - The 'ABPM effect' gradually decreases but does not disappear in successive
      sessions of ambulatory monitoring.
AB  - OBJECTIVES: Previous results have indicated that ambulatory monitoring provides a
      pressor effect on patients using the device for the first time, but not on
      successive sessions of monitoring. Our objective was to validate and quantify the
      extent and duration of this pressor effect in hypertensive patients repeatedly
      evaluated every few months. METHODS: We studied 823 mild-to-moderate hypertensive
      subjects (347 men), 53.4 +/- 14.1 years of age. Blood pressure was measured at 20
      min intervals during the day and at 30-min intervals at night for 48 consecutive
      hours, and physical activity was simultaneously evaluated every minute with a
      wrist actigraph. Forty per cent of the patients were evaluated twice or more.
      RESULTS: In patients evaluated for the first time, results indicated a highly
      statistically significant (P < 0.001) reduction during the second day of
      monitoring as compared to the first in the diurnal mean of systolic and diastolic
      blood pressure, but not in heart rate or physical activity. This pressor effect
      remained statistically significant for the first 10 h of monitoring, independent
      of gender, day of the week of monitoring, or number of antihypertensive drugs
      used by the patients. The nocturnal mean of blood pressure was, however, similar
      between both days of sampling. This 'ambulatory monitoring effect' was
      diminished, although not eliminated, in extent and duration for successive
      sessions of ambulatory monitoring. CONCLUSIONS: Ambulatory monitoring for 48 h
      revealed a statistically significant pressor response that could mostly reflect a
      novelty effect in the use of the monitoring device. This effect has marked
      implications in both research and clinical daily practice for a proper diagnosis
      of hypertension and evaluation of treatment efficacy by the use of ambulatory
      monitoring.

PMID- 14654747
TI  - Effect of oral contraceptives on endothelial function in the peripheral
      microcirculation of healthy women.
AB  - OBJECTIVES: We assessed whether third-generation oral contraceptive (OC)
      treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect
      the endothelial function of healthy women. METHODS: In 20 young healthy women
      (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow
      (strain-gauge plethysmography) changes induced by the intrabrachial infusion of
      acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium
      nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated
      during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L
      arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant
      vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6
      month OC (n = 10) or placebo (n = 10) treatment. RESULTS: In HW the maximal
      vasodilation to ACH, similar between placebo and OC subgroups, was significantly
      reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA
      and unaffected by vitamin C, in both OC and placebo groups. In CW the
      vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P <
      0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein
      cholesterol, and values were similar to those shown by CW. Both OC and placebo
      intake did not change the response to ACH and the modulation induced by L-NMMA or
      vitamin C. Vasodilation to SNP was similar in all groups. CONCLUSIONS: In HW 6
      month treatment with third-generation OC, although associated with an abnormal
      lipid profile, does not adversely affect endothelium-dependent vasodilation. This
      neutral effect could be the balance between a deleterious effect of
      hypercholesterolemia and a protective effect of OC on endothelial function.

PMID- 14654748
TI  - Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy
      humans.
AB  - BACKGROUND: Consumption of flavonoid-rich beverages, including tea and red wine,
      has been associated with a reduction in coronary events, but the physiological
      mechanism remains obscure. Cocoa can contain extraordinary concentrations of
      flavanols, a flavonoid subclass shown to activate nitric oxide synthase in vitro.
      OBJECTIVE: To test the hypothesis that flavanol-rich cocoa induces nitric-oxide
      dependent vasodilation in humans. DESIGN: The study prospectively assessed the
      effects of Flavanol-rich cocoa, using both time and beverage controls.
      Participants were blinded to intervention; the endpoint was objective and
      blinded. METHODS: Pulse wave amplitude was measured on the finger in 27 healthy
      people with a volume-sensitive validated calibrated plethysmograph, before and
      after 5 days of consumption of Flavanol-rich cocoa [821 mg of flavanols/day,
      quantitated as (-)-epicatechin, (+)-catechin, and related procyanidin oligomers].
      The specific nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME) was infused intravenously on day 1, before cocoa, and on day 5, after an
      acute ingestion of cocoa. RESULTS: Four days of flavanol-rich cocoa induced
      consistent and striking peripheral vasodilation (P = 0.009). On day 5, pulse wave
      amplitude exhibited a large additional acute response to cocoa (P = 0.01). L-NAME
      completely reversed this vasodilation (P = 0.004). In addition, intake of
      flavanol-rich cocoa augmented the vasodilator response to ischemia. Flavanol-poor
      cocoa induced much smaller responses (P = 0.005), and none was induced in the
      time-control study. Flavanol-rich cocoa also amplified the systemic pressor
      effects of L-NAME (P = 0.005). CONCLUSION: In healthy humans, flavanol-rich cocoa
      induced vasodilation via activation of the nitric oxide system, providing a
      plausible mechanism for the protection that flavanol-rich foods induce against
      coronary events.

PMID- 14654749
TI  - Evidence for carotid and radial artery wall subclinical lesions in renal
      fibromuscular dysplasia.
AB  - BACKGROUND: Fibromuscular dysplasia (FD) is a non-atherosclerotic, non
      inflammatory arterial disease of unknown cause, and most frequently affects the
      renal and internal carotid arteries. Our objectives were to determine whether
      quantitative and qualitative lesions could be detected by high-resolution
      echotracking techniques at two arterial sites generally considered as free of
      echographic lesions: the common carotid and the radial arteries, and to compare
      their frequency with a control population. METHODS AND RESULTS: We studied 70
      patients with renal FD and 70 control subjects matched for age, sex and systolic
      blood pressure. Arterial parameters were determined using non-invasive high
      resolution echotracking systems. Carotid B-mode scans and radiofrequency signals
      were analysed and quoted by three observers blinded to diagnosis. FD patients had
      thicker carotid (+12%, P < 0.001) and radial arteries (+10%, P < 0.05) than
      controls. Abnormal echographic patterns of the carotid artery, including
      supernumerary interfaces and/or interruption of the blood-intima acoustic
      interfaces, were frequently observed in FD patients and rarely in control
      subjects. These abnormalities were quantified with a phenotypic score ranging
      from 2 to 7, and their sensitivity and specificity were 73 and 81%, respectively,
      as markers of FD. Having a phenotypic score > 3 conferred an odds ratio of 12.9
      (95% CI 5.7-29.3) of having renal FD. CONCLUSION: We defined a new carotid
      phenotype in FD patients using a non-invasive echotracking system, and showed an
      increased wall thickness and distensibility of the radial artery. These data
      indicate the presence of subclinical lesions at arterial sites distant from the
      renal arteries, suggesting that renal FD is not a focal but a systemic arterial
      disease.

PMID- 14654750
TI  - Capillary rarefaction and abnormal cardiovascular reactivity in hypertension.
AB  - OBJECTIVE: To determine the effects of capillary rarefaction on cardiovascular
      reactivity and microcirculatory functioning in essential hypertension. DESIGN:
      Hypertension is associated with abnormal cardiovascular reactivity and increased
      vasoconstriction. Capillary rarefaction amplifies these abnormalities, which
      modify microcirculatory hemodynamics. Hence this study of the hemorheological
      pattern and the veno-arteriolar reflex in hypertensive patients and normotensive
      control subjects. METHODS: Sixty-one men with never-treated essential
      hypertension and capillary rarefaction (< 80 capillaries per field) and 20 age
      matched and sex-matched controls underwent a strenuous cycle ergometer test to
      monitor, during exercise and recovery, the blood pressure profile and the
      hemorheological pattern: blood viscosity at low shear, hematocrit and leukocyte
      counts, soluble P-selectin levels, and red and white blood cell filterability
      rates. The veno-arteriolar reflex was determined by laser-Doppler flowmetry
      before exercise and at recovery.RESULTS Hypertensive men with < or = 72
      capillaries per field had an abnormal hemorheological profile before exercise.
      The physiological response to exercise was observed only in the controls and in
      hypertensives with > or = 73 capillaries per field. Abnormal responses to
      exercise worsened as capillaries were more rarefied. At recovery, hemorheological
      parameters in hypertensives with 65-72 capillaries per field returned to
      baseline, remaining significantly (P < 0.05) different to control values.
      Variations in the hemorheological pattern in hypertensives with < 64 capillary
      per field persisted at recovery. The veno-arteriolar reflex followed the same
      pattern. CONCLUSION: A reduced microvascular network may contribute to abnormal
      cardiovascular reactivity and to exercise-induced rheological abnormalities in
      hypertension.

PMID- 14654751
TI  - Protective effects of dietary potassium chloride on hemodynamics of Dahl salt
      sensitive rats in response to chronic administration of sodium chloride.
AB  - BACKGROUND: Dietary potassium supplementation decreases blood pressure and
      prevents strokes in humans, and prevents strokes and renal damage in Dahl salt
      sensitive (DSS) rats. OBJECTIVE: To study the effects of various concentrations
      of dietary potassium chloride (KCl) on the hemodynamics of Dahl salt-resistant
      (DSR) and DSS rats receiving a 1% sodium chloride (NaCl) diet for 8 months, to
      determine whether there is an optimal dietary concentration of KCl that minimizes
      increases in blood pressure and causes least impairment of blood flow in the
      brain and kidneys. METHODS AND RESULTS: We found a biphasic effect on hemodynamic
      parameters as a function of dietary KCl in DSS rats of the Rapp strain fed 1%
      NaCl with increasing dietary KCl (0.7, 2.6, 4 and 8%). After 8 months receiving a
      diet containing 1% NaCl and 0.7% KCl, DSS rats had mean arterial pressures (MAP),
      plasma volumes, cardiac outputs and renal and cerebral vascular resistances that
      were significantly increased compared with those of DSR rats receiving the same
      diet. With a 2.6% KCl diet, all these parameters were significantly reduced
      compared with those in DSS rats fed the 0.7% KCl diet and were similar to those
      in DSR rats fed 2.6% KCl. Total peripheral resistance in DSR and DSS rats was
      similar on all diets. When KCl was increased to 4 and 8%, MAP, plasma volume,
      cardiac output and renal vascular resistance progressively increased in DSR and
      DSS rats, without changing total peripheral resistance. These changes paralleled
      increases in plasma aldosterone, which resulted from adrenocortical stimulation
      by the increasing dietary KCl; however, cerebral vascular resistance of DSR and
      DSS rats decreased significantly with a 4% KCl diet, despite increased
      aldosterone and sodium retention. Only DSS rats fed a 2.6% KCl diet had
      hemodynamics similar to those of DSR control rats fed the same diet, and
      hyperaldosteronism, sodium retention and increased plasma volume did not occur.
      CONCLUSION: 'Optimal' dietary KCl (2.6%) prevents hypertension and preserves
      cerebral and renal hemodynamics in DSS rats fed a diet containing 1% NaCl for 8
      months, which causes hypertension when dietary KCl is limited or excessive.

PMID- 14654752
TI  - Circulating sodium pump inhibitors in five volume-expanded humans.
AB  - BACKGROUND: We have previously reported the isolation from human placentas of an
      inhibitor of the sodium pump (Na/K ATP-ase) of molecular weight 370 Da, which is
      considered to have a dihydropyrone-substituted steroid (bufenolide) structure.
      OBJECTIVE: To examine if this inhibitor is present outside of the pregnant state.
      METHODS: We examined the plasma ultrafiltrate of patients who were clinically
      volume-expanded. During the period of this study five such patients were
      identified. One was receiving haemofiltration for acute renal failure and four
      were being treated by plasma exchange. High performance liquid chromatograph
      (HPLC) purified fractions obtained from each of these five patients inhibited the
      human leucocyte sodium pump in vitro. RESULTS: Each of the purified fractions
      that inhibited the leucocyte ATP-ase in vitro contained a compound of mass 370
      Da, the same mass as that found previously in placental extracts. This inhibitory
      factor was absent from HPLC purified fractions of plasma ultrafiltrate obtained
      from fifty-five patients who were clinically normovolaemic. Negative ion mass
      spectrometry (MS)/MS of the inhibitory material produced the fragmentation
      pattern characteristic of the placenta-derived pump inhibitor in only one of the
      five samples. The other four samples, although having the same mass, exhibited a
      different fragmentation pattern. CONCLUSION: The results suggest that an
      inhibitor of the sodium pump, identical in mass to that obtained from human
      placentas, circulates in the plasma of volume-expanded patients. The
      fragmentation pattern observed in negative ion mass spectrometry in the majority
      of the volume expanded patients may represent the presence of an isomer of the
      sodium pump inhibitor previously described in placental material.

PMID- 14654753
TI  - Circulating coupling factor 6 in human hypertension: role of reactive oxygen
      species.
AB  - OBJECTIVE: Coupling factor 6 is an endogenous inhibitor of prostacyclin synthesis
      and might function as an endogenous vasoconstrictor in the fashion of a
      circulating hormone in rats. We investigated the role of coupling factor 6 in
      human hypertension. METHODS AND RESULTS: The patients with essential hypertension
      (EH) (n = 30) received a series of normal salt diet (12 g salt/day) for 3 days,
      low salt diet (2 g salt/day) for 7 days, and high salt diet (20-23 g salt/day)
      for 7 days. Normotensive control subjects (n = 27) received normal and low salt
      diets. The plasma level of coupling factor 6, measured by radioimmunoassay,
      during normal salt diet was higher in patients with EH than in normotensive
      subjects (17.6 +/- 1.7 versus 12.8 +/- 0.5 ng/ml, P < 0.01). Whereas the plasma
      level of coupling factor 6 was unchanged after salt restriction in normotensive
      subjects, it was decreased after salt restriction (from 12 g/day to 2 g/day) and
      was increased after salt loading (from 2 g/day to 20-23 g/day) in patients with
      EH. This increase in plasma level of coupling factor 6 was abolished by oral
      administration of ascorbic acid, but the level of blood pressure was unaffected.
      The percentage changes in plasma coupling factor 6 level after salt restriction
      and loading were positively correlated with those in mean blood pressure (r =
      0.57, P < 0.01), and negatively correlated with those in plasma nitric oxide
      level (r = -0.51, P < 0.05). CONCLUSION: These indicate that circulating coupling
      factor 6 is elevated in human hypertension and modulated by salt intake
      presumably via reactive oxygen species.

PMID- 14654754
TI  - Homocysteine and red blood cell glutathione as indices for middle-aged untreated
      essential hypertension patients.
AB  - OBJECTIVE: Intracellular glutathione in its reduced state is a principal cellular
      biomolecule with antioxidant activity. Glutathione and homocysteine metabolism
      are closely associated. As both oxidative stress and hyperhomocystinemia are
      associated with hypertension, we assessed the relationships between these
      variables. DESIGN AND SETTING: An observation-based case-control study, performed
      at a university teaching hospital. PATIENTS: Middle-aged male patients with
      untreated uncomplicated essential hypertension (mean +/- standard deviation age
      53.0 +/- 7.2 years, n = 48) before any treatment and controls with similar age
      distributions (age 51.6 +/- 5.5 years, n = 28) were evaluated. METHODS: In all
      subjects, the plasma levels of homocysteine, lipids, creatinine, protein, and
      glucose were measured. Reduced and oxidized glutathione and folic acid were
      measured from red blood cells (RBC). RESULTS: The hypertensive patients had
      decreased levels of red blood cell reduced glutathione (RBC-GSH) and increased
      levels of oxidized glutathione, which resulted in elevated ratio of
      oxidized/reduced glutathione as compared to controls (P < 0.001). Plasma
      homocysteine levels were significantly higher in the hypertensive patients versus
      the age-matched controls (P < 0.004). In the hypertensive patients, RBC-GSH
      correlated inversely with systolic blood pressure, serum creatinine, protein and
      RBC folic acid. No correlation was detected between RBC-GSH and homocysteine. In
      the controls, RBC-GSH correlated inversely with homocysteine, RBC folic acid and
      creatinine. According to multiple regression, in the hypertensive patients RBC
      GSH was related to systolic blood pressure, hemoglobin, plasma homocysteine,
      creatinine and protein. Such a relationship was not detected for the controls.
      CONCLUSION: In untreated hypertensive patients both homocysteine and systolic
      blood pressure are associated with intracellular oxidative stress as determined
      by RBC-GSH.

PMID- 14654755
TI  - Superoxide does not mediate the acute vasoconstrictor effects of angiotensin II:
      a study in human and porcine arteries.
AB  - OBJECTIVE: To investigate whether superoxide mediates angiotensin (Ang) II
      induced vasoconstriction. METHODS: Human coronary arteries (HCAs), porcine
      femoral arteries (PFA) and porcine coronary arteries (PCAs) were mounted in organ
      baths and concentration-response curves to Ang II, the nitric oxide (NO) donor S
      nitroso-N-acetylpenicillamine (SNAP) and the NAD(P)H oxidase substrate NADH were
      constructed in the absence and presence of superoxide inhibiting and activating
      drugs. Extracellular superoxide was measured using cytochrome c reduction.
      RESULTS: Ang II constricted both HCAs and PFAs. In HCAs, the NAD(P)H inhibitors
      diphenyleneiodonium (DPI) and apocynin, and the xanthine oxidase (XO) inhibitor
      allopurinol, but not the superoxide dismutase (SOD) mimetic tempol or the SOD
      inhibitor diethyldithiocarbamate (DETCA), reduced this constriction. Catalase
      potentiated Ang II in HCAs, indicating a vasodilator role for H2O2. DPI, tempol
      and SOD did not affect Ang II in PFAs. DPI, apocynin and allopurinol relaxed
      preconstricted HCAs. Although the relaxant effects of the NO donor SNAP in PCAs
      was reduced by DETCA, indicating that superoxide-induced constrictions depend on
      NO inactivation, the apocynin-induced relaxations were NO independent. Moreover,
      NADH relaxed all vessels, and this effect was blocked by KCl but not DPI or NO
      removal. Xanthine plus XO also relaxed HCAs and PCAs. Incubation of human or
      porcine arteries with Ang II or NADH did not result in detectable increases of
      extracellular superoxide within 1 h. CONCLUSIONS: Acute vasoconstriction by Ang
      II is not mediated via superoxide generated through NAD(P)H oxidase and/or XO
      activation. Such activation, if occurring, rather results in the generation of
      the vasodilator H2O2.

PMID- 14654756
TI  - Adrenergic mechanisms and remodeling of subcutaneous small resistance arteries in
      humans.
AB  - BACKGROUND: Vascular structural alterations in small resistance arteries of
      patients with essential hypertension (EH) are mostly characterized by inward
      eutrophic remodeling. In fact, no difference in the smooth muscle cell volume
      (CV) between normotensive subjects (NT) and essential hypertensive patients was
      observed. However, experimental models of hypertension with chronic infusion of
      agonists of adrenergic receptors were characterized by the presence of smooth
      muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence
      of vascular smooth muscle cell hypertrophy in patients with renovascular
      hypertension. OBJECTIVE: The aim of the study to investigate the structural
      characteristics of subcutaneous small resistance arteries of NT, of EH, and of
      patients with phaeochromocytoma (Phaeo). PATIENTS AND METHODS: Thirty Phaeo, 30
      NT and 30 EH were included in the study. A biopsy of subcutaneous fat was taken
      from all subjects. Small resistance arteries (relaxed diameter 160-280 microm)
      were dissected and mounted on a micromyograph and the media : lumen ratio was
      calculated. In nine Phaeo, nine NT and 13 EH the cell volume was measured by an
      unbiased stereological principle, the 'disector' method. RESULTS No difference in
      smooth muscle cell volume was observed between groups. However, inward remodeling
      in Phaeo was less marked than in EH, although the increase in media : lumen ratio
      was similar compared with NT. However, the lack of changes in media cross
      sectional area, compared with NT, suggest that there has been little hypertrophy,
      the changes observed thus being eutrophic. CONCLUSIONS: Our data show, based on a
      reasonably large sample, that a pronounced activation of the adrenergic system is
      not associated with vascular smooth muscle cell hypertrophy or hyperplasia in
      humans. It is therefore possible that adrenergic mechanisms may have a relevant
      role in the development of eutrophic remodeling in small vessels.

PMID- 14654757
TI  - Entacapone protects from angiotensin II-induced inflammation and renal injury.
AB  - OBJECTIVES AND DESIGN: Angiotensin II (Ang II)-induced renal damage is associated
      with perivascular inflammation and increased oxidative stress. We tested the
      hypothesis whether entacapone, a catechol-O-methyltransferase (COMT) inhibitor
      exerting antioxidative and anti-inflammatory properties, protects against the Ang
      II-induced inflammatory response and end-organ damage. METHODS: Samples from
      double-transgenic rats harbouring human renin and human angiotensinogen genes
      (dTGR) and normotensive Sprague-Dawley rats (SD) were assessed by light
      microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction
      (RT-PCR), and high pressure liquid chromatography. The effects of entacapone
      treatment for 3 weeks were examined in dTGR and SD. RESULTS: Entacapone
      completely prevented cardiovascular mortality and decreased albuminuria by 85% in
      dTGR. Entacapone ameliorated Ang II-induced vascular and glomerular damage,
      leucocyte infiltration, and intercellular adhesion molecule-1 (ICAM-1)
      overexpression in the kidneys. Serum 8-isoprostane concentration, as well as
      renal nitrotyrosine and 8-hydroxydeoxyguanosine expressions, all markers of
      oxidative stress, were markedly increased in dTGR and normalized by entacapone.
      Entacapone also decreased p22phox mRNA expression in the kidney. COMT expression
      was increased by 500% locally in the renal vascular wall in dTGR; however, COMT
      activity in the whole kidney remained unchanged. Urinary dopamine excretion, a
      marker of renal dopaminergic tone, was decreased by 50% in untreated dTGR. Even
      though entacapone decreased renal COMT activity by 40%, the renal dopaminergic
      tone remained unchanged in entacapone-treated dTGR. CONCLUSION: Our findings
      suggest that entacapone provides protection against Ang II-induced renal damage
      through antioxidative and anti-inflammatory mechanisms, rather than by COMT
      inhibition-induced changes in renal dopaminergic tone.

PMID- 14654758
TI  - Resistance to salt-induced hypertension in catechol-O-methyltransferase-gene
      disrupted mice.
AB  - BACKGROUND: Previous studies have indicated that catechol-O-methyltransferase
      (COMT) can modulate renal dopaminergic tone. OBJECTIVE: To test the hypothesis
      that COMT blockade protects from salt-induced hypertension. METHODS: COMT gene
      disrupted (-/-) mice and wild-type controls received a high-sodium diet (NaCl 6%)
      for 3 weeks. Blood pressure and heart rate were recorded by radiotelemetry.
      Tissue and urine samples were assessed by light microscopy and high-performance
      liquid chromatography. The effects of nitecapone treatment were also examined.
      Systolic blood pressure and heart rate during normal sodium diet were similar in
      COMT (-/-) and wild-type mice. The high-sodium diet increased night-time systolic
      and diastolic blood pressures in wild-type mice, whereas blood pressure in COMT (
      /-) mice remained unaltered. In wild-type mice, the sodium-induced increase in
      blood pressure was completely normalized by treatment with the COMT inhibitor,
      nitecapone. At baseline, 24-h urinary excretion of levodopa (L-DOPA), dopamine
      and noradrenaline was increased by 145, 85 and 74%, respectively, in COMT (-/-)
      mice compared with wild-type controls. In COMT (-/-) and wild-type mice, a high
      sodium diet increased urinary L-DOPA excretion by 405 and 660% (reflected as 102
      and 212% increases in dopamine excretion), respectively. The absolute amounts of
      urinary L-DOPA and dopamine remained 60 and 20% greater in COMT (-/-) mice. The
      high-sodium diet did not influence renal cortical COMT activity. CONCLUSION: Our
      findings suggest that COMT deficiency in mice increases the availability of L
      DOPA, leading to enhanced dopaminergic tone, which may be associated with
      resistance to salt-induced hypertension. The findings of the present study also
      underline the importance of COMT in the regulation of blood pressure, sodium
      excretion and renal dopaminergic tone.

PMID- 14654759
TI  - Distribution of nitric oxide synthases and nitrotyrosine in the kidney of
      spontaneously hypertensive rats.
AB  - OBJECTIVES: To study the cellular distribution and the expression of the major
      isoforms of NO synthase (NOS) and of nitrotyrosine in the kidney in spontaneous
      hypertension. DESIGN AND METHODS: We have studied by immunohistochemistry the
      location of the endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) isoforms
      and nitrotyrosine in kidney slices from normotensive Wistar-Kyoto (WKY) rats and
      spontaneously hypertensive rats (SHR) using specific antibodies. In order to
      quantify the expression of these proteins, we have analyzed dissected renal
      cortical and medullary sections by means of Western blot. RESULTS: Tubular cells
      were immunoreactive to nNOS and more numerous in the renal medulla of the SHR
      compared with that of the WKY, specifically in the outer medulla and the
      papillary region. Western blot also showed higher expression of nNOS in the renal
      medulla, but not the renal cortex of the SHR. In contrast, iNOS and eNOS
      distribution and expression were similar in the kidneys of WKY rats and SHR.
      Immunohistochemistry showed immunoreactive cells to nitrotyrosine in a variety of
      renal cells similarly distributed in SHR and WKY kidneys. Western analysis
      detected three proteins of 14.5, 23.7 and 39 kDa immunoreactive to nitrotyrosine,
      showing a higher expression in the renal cortex compared to the renal medulla.
      CONCLUSIONS: The expression of nNOS is higher in the renal medulla of the SHR,
      and the distribution of eNOS, iNOS and nitrotyrosine is similar in SHR and WKY
      rats. It is proposed that the higher expression of the neuronal isoform in the
      medullary tubular cells is a protective mechanism aimed to improve renal function
      in spontaneous hypertension.

PMID- 14654760
TI  - Renal damage is not improved by blockade of endothelin receptors in primary renin
      dependent hypertension.
AB  - OBJECTIVE: Secondary activation of the renin-angiotensin system plays a major
      role in the progression of chronic nephropathies, and blockade of endothelin (ET)
      receptors has been shown to confer nephroprotection in experimental models of
      proteinuric renal disease. We tested the nephroprotective potential of selective
      endothelin A receptor (ETA) and non-selective ETA and endothelin B (ETA/B)
      receptor blockade in the TGR(mRen2)27 transgenic rat model with renin-dependent
      hypertension (Ren2). DESIGN: Ren2 animals were treated between 10 and 30 weeks of
      age with the selective ETA receptor antagonist darusentan (Ren2-ETA) and the
      ETA/B receptor antagonist Lu420627 (Ren2-ETA/B), and compared with transgene
      negative Sprague-Dawley (SD) controls. Since the elevated systolic blood pressure
      in Ren2 was not affected in either Ren2-ETA or Ren2-ETA/ETB, an additional Ren-2
      group was treated with a non-antihypertensive dose of the angiotensin II type 1
      receptor blocker eprosartan (Ren2-AT1). RESULTS: During the 20-week observation
      period 35% of untreated Ren2, 30% of Ren2-ETA/B, 50% of Ren2-ETA, and 83% of Ren2
      AT1 animals survived compared with 100% of SD rats. Renal endothelin-1 mRNA
      expression and proteinuria (4.1-fold) were significantly elevated in Ren2
      compared with SD rats (P < 0.05, respectively). Proteinuria was normalized to SD
      control levels in Ren2-AT1 (P < 0.05) but increased further in Ren2-ETA (7.7
      fold) and Ren2-ETA/B (15-fold) (P < 0.05, respectively). Glomerulosclerosis,
      tubulointerstitial damage and renal osteopontin mRNA expression were reduced in
      Ren2-AT1 (P < 0.05, respectively) but remained unchanged or increased further in
      Ren2-ETA and Ren2-ETA/B compared with Ren2. CONCLUSION: ET receptor blockade
      fails to improve renal damage and mortality in primary renin-dependent
      hypertension.

PMID- 14654761
TI  - Additive effects of hypertension and diabetes on renal cortical expression of PKC
      alpha and -epsilon and alpha-tubulin but not PKC-beta 1 and -beta 2.
AB  - OBJECTIVE: This study examined the separate and combined effects of hypertension
      and diabetes on renal cortical expression of protein kinase C (PKC) isoforms 
      beta 1, -beta 2, -alpha and -epsilon, to determine whether albuminuria is the
      result of an increase in the expression of one or a combination of PKC isoforms.
      Corresponding changes in renal microtubules were also assessed. METHODS: Diabetes
      (D) was induced in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)
      by streptozotocin. After 24 weeks, PKC expression was determined by Western blot
      and microtubules were assessed by immunohistochemistry for alpha-tubulin protein.
      RESULTS: Diabetes was characterized by significant increases in glycated
      haemoglobin (HbA1c) as compared to controls (C). There was a significant increase
      of three- to four-fold in PKC protein content for all four isoforms in renal
      cortex from SHR-C and WKY-D, and similar and significant levels of albuminuria
      (approximately 10 mg/24 h) observed in these groups in comparison to WKY-C
      (approximately 1 mg/24 h). Interestingly, PKC-alpha and -epsilon but not PKC-beta
      1 and -beta 2 protein content was doubled in SHR-D, and albuminuria increased
      tenfold (approximately 100 mg/24 h) in comparison to SHR-C and WKY-D. These
      changes were paralleled by a significant decrease in alpha-tubulin protein
      content of approximately 50% in SHR-C and approximately 33% in WKY-D compared to
      WKY-C, with a further decrease of approximately 67% in SHR-D compared to WKY-C.
      CONCLUSION: These findings indicate that PKC expression can be increased by
      either diabetes or hypertension, and that there are further specific increases in
      the expression of PKC isoforms -alpha and -epsilon in the model of combined
      diabetes and hypertension. In addition, the degree of disruption in microtubular
      cytoskeleton appears to be correlated with PKC activation and levels of
      albuminuria.

PMID- 14654762
TI  - Results of the pilot study for the Hypertension in the Very Elderly Trial.
AB  - BACKGROUND: The risks and benefits of treating hypertension in individuals older
      than 80 years are uncertain. A meta-analysis has suggested that a reduction in
      stroke events of 36% may have to be balanced against a 14% increase in total
      mortality. OBJECTIVES: To report the results of the pilot study of the
      Hypertension in the Very Elderly Trial (HYVET), which is in progress to address
      these issues. METHODS: The HYVET-Pilot was a multicentre international open pilot
      trial. In 10 European countries, 1283 patients older than 80 years and with a
      sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of
      three treatments: a diuretic-based regimen (usually bendroflumethiazide; n =
      426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n =
      431) or no treatment (n = 426). The procedure permitted doses of the drug to be
      titrated and diltiazem slow-release to be added to active treatment. Target blood
      pressure was < 150/80 mmHg and mean follow-up was 13 months. RESULTS: In the
      combined actively treated groups, the reduction in stroke events relative hazard
      rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction
      in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of
      total mortality supported the possibility of excess deaths with active treatment
      (RHR 1.23, 95% CI 0.75 to 2.01). CONCLUSIONS: The preliminary results support the
      need for the continuing main HYVET trial. It is possible that treatment of 1000
      patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be
      associated with 20 extra non-stroke deaths.

PMID- 14654763
TI  - Transdermal 17 beta-oestradiol reduces salt sensitivity of blood pressure in
      postmenopausal women.

PMID- 14654764
TI  - Invasive Streptococcus pyogenes after allograft implantation--Colorado, 2003.
AB  - Allograft tissues are used for various orthopedic procedures (e.g., ligament
      reconstruction, meniscal transplantation, and spinal surgery). In 2002,
      approximately one million allografts were distributed for transplantation
      (American Association of Tissue Banks [AATB], unpublished data, 2002). Recent
      reports of allograft-associated infections have prompted evaluation of the
      processing and quality-control methods employed by tissue processors. This report
      describes a case of invasive disease with Streptococcus pyogenes (i.e., group A
      streptococcus [GAS]), after reconstructive knee surgery using contaminated
      allograft tissue and provides recommendations to reduce the risk for allograft
      associated infections. Although allograft infections are rare, they highlight the
      need for improved tissue evaluation and processing standards.

PMID- 14654765
TI  - Clostridial endophthalmitis after cornea transplantation--Florida, 2003.
AB  - Endophthalmitis is a severe condition caused by inflammation of the ocular cavity
      that often is associated with infection of the internal structures of the eye.
      The source of infection can include bacteria disseminated through the bloodstream
      and contamination of the cornea at the time of ocular surgery or trauma.
      Complications include rapid, reversible vision loss that can progress quickly to
      panophthalmitis, requiring surgical removal of the eye. Clostridium perfringens,
      an anaerobic gram-positive bacillus found in soil and bowel flora, is an
      infrequent cause of endophthalmitis. Although the majority of cases are caused by
      penetrating injury with soil-contaminated foreign bodies, C. perfringens
      endophthalmitis has been reported in patients after cataract surgery. This report
      describes two cases of C. perfringens endophthalmitis that occurred within 24
      hours after transplant of contaminated corneas. These cases demonstrate the
      potential for transmission of Clostridium infection from donor to recipient.
      Clinicians should be aware of potential infection risks associated with
      transplantation of corneal tissues and report any infections to the appropriate
      eye bank.

PMID- 14654766
TI  - Update: Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts-
      Japan, 1979-2003.
AB  - In 1997, a nongovernment surveillance group for Creutzfeldt-Jakob disease (CJD)
      in Japan supported financially by the Ministry of Health and Welfare (MHW)
      reported 43 cases of CJD associated with receipt of cadaveric dura mater grafts.
      In all but one case, the most probable vehicle of transmission was a single brand
      of dural graft (LYODURA [B. Braun Melsungen AG, Melsungen, Germany]) produced
      before May 1987. As of March 2003, ongoing surveillance in Japan had identified
      an additional 54 dura mater graft--associated cases. This report summarizes the
      investigation of the 97 cases, which indicated that during 1983-1987, the
      estimated minimum risk for CJD within 17 years of receipt of the implicated
      product in Japan was approximately one case per 1,250 grafts. No cases have been
      reported among patients who received their first dural graft after 1991; however,
      because of the long latency period between graft placement and symptom onset,
      additional cases of graft-associated CJD are likely to be reported.

PMID- 14654767
TI  - Partner counseling and referral services to identify persons with undiagnosed HIV
      -North Carolina, 2001.
AB  - Approximately one fourth of the 850,000-950,000 persons living with human
      immunodeficiency virus (HIV) in the United States are not aware of their
      infection and their risk for transmitting HIV. Identifying HIV-infected persons
      promptly after infection and directing them to medical care and prevention
      services is a national priority. Voluntary partner counseling and referral
      services (PCRS) help HIV-infected persons notify sex and needle-sharing partners
      of their need for HIV testing, enabling partners to receive early care and
      prevention counseling. To evaluate the success of these services in North
      Carolina, CDC analyzed PCRS data collected in 2001 by the North Carolina
      Department of Health and Human Services (NCDHHS). This report summarizes the
      results of that analysis, which determined that 125 (20.5%) of 610 tested
      partners of HIV index patients had HIV infections that were undiagnosed
      previously. These findings suggest that local and state health departments should
      consider PCRS an essential component of any comprehensive HIV-prevention program.

PMID- 14654768
TI  - Public health dispatch: tuberculosis outbreak in a homeless population--Portland,
      Maine, 2002-2003.
AB  - During June 2002-July 2003, seven men with active pulmonary tuberculosis (TB)
      disease in Portland, Maine, were reported to the Maine Bureau of Health (MBH).
      Six were linked through residence at homeless shelters; four had matching
      Mycobacterium tuberculosis genotypes. Prompt investigation and identification of
      approximately 1,100 contacts likely prevented further spread of TB. This report
      summarizes preliminary results of the ongoing investigation and MBH efforts to
      work with health-care providers statewide to improve early detection of TB among
      homeless persons.

PMID- 14654770
TI  - Innovators in urology. Abstracts of the 5th International Meeting. 6-8 June 2003,
      Amsterdam, The Netherlands.

PMID- 14654769
TI  - Altered KSPG expression by keratocytes following corneal injury.
AB  - PURPOSE: Keratocytes synthesize keratan-sulfate proteoglycans (KSPG), lumican and
      keratocan, to develop and maintain proper collagen interfibrillar spacing and
      fibril diameter characteristics of the transparent cornea. The purposes of this
      study are to compare the expression patterns of KSPGs and keratin 12 (K12)
      respectively by corneal keratocytes and epithelial cells after three different
      types of injuries; partial and total epithelial debridement and alkali burn.
      METHODS: Corneas of 8-12 week old C57Bl/6J or FVBN mice were wounded by partial
      epithelial (2 mm in diameter) and total epithelial debridement, and alkali burn
      (0.1 M NaOH, 30 s) and were allowed to heal for various periods of time, from 1
      to 84 days. The corneas were then subjected to light microscopy, in situ and
      Northern hybridization and RT-PCR for examining the expression of K12 and KSPG in
      the corneal epithelium and stroma, respectively. Immunohistochemistry with anti
      alpha-smooth muscle actin (alpha-SMA) was used to identify myofibroblasts in the
      stroma of injured cornea. RESULTS: In 2-3 days, partial epithelial denuded
      corneas were resurfaced by corneal epithelium positive for K12, and stromal edema
      caused by debridement disappeared. Total epithelial debridement wounded corneas
      were resurfaced by conjunctival epithelial cells in 2 weeks. Stromal edema in the
      total epithelial debridement corneas began to subside after 6 weeks. Corneal
      epithelial cells resurfaced alkali burned corneas within 3-5 days. In situ and
      Northern hybridization showed a decrease in keratocan and lumican expression at 6
      weeks and increased at 12 weeks post-injury in all wound types. Alpha-SMA
      positive myofibroblasts in the cornea were detected via immunostaining at the
      time point when KSPG expression was lowest, 6 weeks post-injury. CONCLUSIONS: The
      results suggest keratocan and lumican are down-regulated during wound healing at
      6 weeks and returned to higher levels at 12 weeks post-injury; implicating that
      the cells repopulating the injured corneal stroma regained the characteristic
      function of keratocytes independent of the wound types. However, complete
      epithelial removal results in irreversible loss of K12 expression.

PMID- 14654777
TI  - Inhibition of choline kinase as a specific cytotoxic strategy in oncogene
      transformed cells.
AB  - Cancer treatment is in the need of selective drugs that can interfere
      specifically with signalling pathways affected during the carcinogenic process.
      Identification of new potential molecular targets is the key event in the design
      of new anticancer strategies. Once identified, attempts for the generation of
      specific molecules to regulate their function can be achieved. The relevance of
      deregulation of choline kinase (ChoK, E.C. 2.7.1.32) in oncogene-driven cell
      transformation has been previously demonstrated. Here we provide strong evidence
      that MN58b, a selective inhibitor of ChoK, is rather specific to this enzyme,
      with no effect on a variety of oncogene-activated signalling pathways involved in
      the regulation of cell proliferation. MN58b does not affect MAPKs, PI3K, and
      other enzymes involved in the regulation of phospholipid metabolism such as
      phospholipases C, D, and A2, CTP:phosphocholine cytidylyltransferase, or
      diacylglycerol choline-phosphotransferase. Consistent with this specificity,
      ectopic expression of ChoK resulted in resistance to its inhibitor. Finally,
      nontransformed cells were able to resume cell proliferation after removal of the
      drug, while transformed cells were irreversibly affected. These results indicate
      that inhibition of ChoK is a rather specific strategy for the cytotoxic treatment
      of transformed cells.

PMID- 14654778
TI  - Opposite long-term regulation of c-Myc and p27Kip1 through overactivation of Raf
      1 and the MEK/ERK module in proliferating human choroidal melanoma cells.
AB  - Although there is no current evidence for ras gene mutation in choroidal
      melanoma, there is an increasing body of evidence indicating that deregulated
      intracellular signalling pathways are involved in choroidal melanoma
      pathogenesis. The various components of the linear Raf/MEK/ERK signalling pathway
      have been implicated in various tumours. We therefore investigated the role of
      Raf-1 and the MEK/ERK module in the proliferation of human normal choroidal
      melanocytes (NCM) and cells from the ocular choroidal melanoma (OCM-1) cell line.
      OCM-1 cells proliferated four times faster than NCM. High basal activation of the
      MEK/ERK module was observed in unstimulated OCM-1 cells, whereas rapid and
      persistent activation was detected after serum stimulation, throughout the 24-h
      period of culture. In contrast, the activation of MEK/ERK was barely detectable
      in unstimulated NCM and occurred late (6 h) after the stimulation of cell
      proliferation. Inhibition of Raf-1 and MEK1/2 activation by pharmacological
      approaches and of the production of Raf-1 and ERK1/2 by antisense oligonucleotide
      approaches demonstrated that Raf-1 and the MEK/ERK module controlled
      proliferation in OCM-1 cells, but not in NCM. OCM-1 cells produced very low
      levels of p27Kip1, whereas NCM produced constant, high levels of p27Kip1. The
      inhibition of Raf-1 or MEK1/2 induced a large increase in p27Kip1 in OCM-1 cells,
      associated with an arrest of cell proliferation. Levels of c-Myc production were
      high and constant in OCM-1 cells and low in NCM, in contrast to what was observed
      for p27Kip1. The inhibition of both Raf-1 and MEK1/2 induced a decrease in c-Myc
      production and downregulated c-Myc activity by preventing c-Myc phosphorylation
      in OCM-1 cells. We conclude that Raf-1 and the MEK/ERK module control the
      production of both p27Kip1 and c-Myc, and the activation of c-Myc for OCM-1 cell
      proliferation.

PMID- 14654779
TI  - Identification of novel ERK-mediated feedback phosphorylation sites at the C
      terminus of B-Raf.
AB  - The extracellular signal-regulated kinase (ERK) pathway plays an important role
      during the development and activation of B lymphocytes. We have recently shown
      that B-Raf is a dominant ERK activator in B-cell antigen receptor signalling. We
      now show that B-Raf is hyperphosphorylated upon BCR engagement and undergoes a
      prominent electrophoretic mobility shift. This shift correlates with ERK
      activation and is prevented by the MEK inhibitor U0126. Syk-deficient DT40 B
      cells display neither dual ERK phosphorylation nor a mobility shift of B-Raf upon
      BCR engagement. The inducible expression of a constitutively active B-Raf in this
      mutant line restores dual ERK phosphorylation and the mobility shift of
      endogenous B-Raf, indicating that these two events are connected to each other.
      By site-directed mutagenesis studies, we demonstrate that the shift is due to an
      ERK2-mediated feedback phosphorylation of serine/threonine residues within an
      evolutionary conserved SPKTP motif at the C-terminus of B-Raf. Replacement of
      these residues by negatively charged amino acids causes a constitutive mobility
      shift and a reduction of PC12 cell differentiation. We discuss a model in which
      ERK-mediated phosphorylation of the SPKTP motif is involved in negative feedback
      regulation of B-Raf.

PMID- 14654780
TI  - SIAH-1 interacts with CtIP and promotes its degradation by the proteasome
      pathway.
AB  - SIAH-1 and SIAH-2 are the human members of an evolutionary highly conserved E3
      ligase family. SIAH-1 is a p53 and p21(Waf-1/Cip-1) induced gene during apoptosis
      and tumor suppression. In stable-transfected clones of MCF-7 cells, SIAH-1
      overexpression was associated with apoptosis, mitotic alterations and p21(Waf
      1/Cip-1) induction of expression. Using a two-hybrid screening, we identified
      here the transcriptional corepressor CtBP-interacting protein (CtIP) as a SIAH-1
      interacting protein. CtIP has been proposed as a regulator of p21(Waf-1/Cip-1)
      gene transcription through a protein complex involving BRCA1. We demonstrate that
      SIAH-1 associates with CtIP both in vitro and in vivo. This interaction led to
      CtIP degradation by the ubiquitin-proteasome pathway. As expected, SIAH-1 induced
      p21(Waf-1/Cip-1) transcription in Jurkat-T cell. Surprisingly, a SIAH protein
      deleted of its RING finger, SIAH-1DeltaN, which is able to interact with CtIP but
      does not promote its degradation, also induced transcription from the p21(Waf-1)
      promoter in a similar extent as did SIAH-1. Our results suggest that p21(Waf
      1/Cip-1) induction by SIAH-1 could not be mediated by CtIP degradation.

PMID- 14654781
TI  - c-CBL is not required for leukemia induction by Bcr-Abl in mice.
AB  - Bcr-Abl tyrosine kinase activity is essential for the pathogenesis of chronic
      myeloid leukemia (CML). A number of Bcr-Abl substrates have been identified, but
      it is not clear which of these substrates are required for Bcr-Abl to transform
      cells. The multifunctional protein c-Cbl is one of the most prominently tyrosine
      phosphorylated proteins in Bcr-Abl-expressing cells. Using cell lines and mice
      with homozygous disruption of the c-CBL locus, we investigated the role of this
      protein for Bcr-Abl-driven transformation. We find that although c-Cbl(-/-)
      fibroblast cell lines show a deficit in Bcr-Abl transformation compared to wild
      type (Wt) cells, this deficit was less pronounced in c-Cbl(-/-) B cells derived
      from murine bone marrow. Most importantly, in a transplantation model of CML, Bcr
      Abl was capable of inducing fatal leukemia in mice in the absence of c-Cbl
      protein. Our results indicate that c-Cbl is dispensable for Bcr-Abl-induced
      leukemogenesis in mice.

PMID- 14654782
TI  - Inhibition of Rho pathways induces radiosensitization and oxygenation in human
      glioblastoma xenografts.
AB  - We previously demonstrated in vitro that inhibiting the biological pathways of
      the small GTPase Rho radiosensitizes the human glioma U87 cell line. The aim of
      this study was to determine if Rho might be involved in the control of in vivo
      radiosensitivity altogether by controlling cellular radioresistance and by
      modifying tumor microenvironment. We demonstrate here that the in vivo induction
      of the dominant negative of Rho, RhoBN19, in U87 xenografts induces a significant
      decrease of tumor cell survival after irradiation more important than the one we
      previously observed in vitro. This in vivo increased effect of RhoBN19 expression
      is due to the improvement of the tumor oxygenation associated with a significant
      decrease of the vessel density and of the metalloproteinase 2 (MMP2) expression.
      Moreover, in vitro RhoBN19 expression in U87 cells leads to the inhibition of
      MMP2 activity. Our results demonstrate for the first time that inhibiting Rho
      pathways modifies the in vivo radiosensitivity of human glioma cells by
      controlling intrinsic radioresistance, hypoxia and angiogenesis. These data
      strongly suggest that Rho should be a major determinant of cellular resistance to
      ionizing radiation.

PMID- 14654783
TI  - Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear
      export.
AB  - Mdm2 oncoprotein plays a major role in inhibiting the p53 tumor suppressor
      protein. Here, we investigate phosphorylation of Mdm2 at serine 407 (S407). S407
      is phosphorylated in cells after treatment with camptothecin (CPT) or
      hydroxyurea, inhibitors of DNA replication. S407 phosphorylation after CPT
      treatment is induced upon cell cycle arrest during S phase and prevented if entry
      into S phase of cell cycle is blocked. We found that a major kinase responsible
      for S407 phosphorylation is ATR, a DNA damage checkpoint protein that induces
      cell cycle arrest and promotes DNA repair in response to impaired DNA
      replication; induction of S407 phosphorylation is enhanced after expression of
      wild-type ATR, while it is inhibited by a dominant-negative form of ATR. Further,
      S407 is specifically phosphorylated by ATR in vitro. Substitution of S407 with
      aspartate (S407D), but not with alanine (S407A), promotes nuclear localization of
      p53. Taken together, our data indicate that S407 phosphorylation of Mdm2 by ATR
      reduces Mdm2-dependent export of p53 from nuclei to cytoplasm.

PMID- 14654784
TI  - Cyclic adenosine 3',5'-monophosphate-elevating agents inhibit transforming growth
      factor-beta-induced SMAD3/4-dependent transcription via a protein kinase A
      dependent mechanism.
AB  - Transforming growth factor-beta (TGF-beta) plays complex roles in carcinogenesis,
      as it may exert both tumor suppressor and pro-oncogenic activities depending on
      the stage of the tumor. SMAD proteins transduce signals from the TGF-beta
      receptors to regulate the transcription of specific target genes. Crosstalks with
      other signaling pathways may contribute to the specificity of TGF-beta effects.
      In this report, we have investigated the effects of cyclic adenosine 3',5'
      monophosphate (cAMP), a key second messenger in the cellular response to various
      hormones, on SMAD-dependent signaling in human HaCaT keratinocytes. Using either
      an artificial SMAD3/4-dependent reporter construct or the natural TGF-beta
      target, plasminogen activator inhibitor-1, we show that membrane-permeable
      dibutyryl cAMP, and other intracellular cAMP-elevating agents such as the
      phosphodiesterase inhibitor isobutyl-methylxanthine, the adenylate cyclase
      activator forskolin, or exogenous prostaglandin E2 (PGE2), interfere with TGF
      beta-induced SMAD-specific gene transactivation. Inhibition of protein kinase A
      (PKA), the main downstream effector of cAMP, with H-89, suppressed cAMP-dependent
      repression of SMAD-driven gene expression. Inversely, coexpression of either an
      active PKA catalytic subunit or that of the cAMP response element (CRE)-binding
      protein (CREB) blocked SMAD-driven gene transactivation. cAMP-elevating agents
      did not inhibit nuclear translocation and DNA binding of SMAD3/4 complexes, but
      abolished the interactions of SMAD3 with the transcription coactivators CREB
      binding protein (CBP) and p300 in a PKA-dependent manner. These results suggest
      that suppression of TGF-beta/SMAD signaling and resulting gene transactivation by
      cAMP-inducing agents occurs via PKA-dependent, CREB-mediated, disruption of SMAD
      CBP/p300 complexes.

PMID- 14654785
TI  - c-Jun and the dominant-negative mutant, TAM67, induce vimentin gene expression by
      interacting with the activator Sp1.
AB  - Vimentin exhibits a complex pattern of developmental- and tissue-specific
      expression. Since it is aberrantly expressed in metastatic tumors, which have
      progressed through the epithelial-mesenchymal transition, it has been cited as a
      marker for tumor progression. Previous studies have indicated that the
      transcription factor activator protein (AP1) is important in tumor progression.
      The stable transformation of the MCF7 cell line with the oncogene c-Jun resulted
      in a cell line (MCF7Jun), which displayed a change in morphology, enhanced
      migratory and invasive properties, and metastatic behavior. Of the 21 genes whose
      expression levels were altered in the MCF7Jun cell line, the greatest change in
      expression occurred for the vimentin gene. Previously, tandem AP1 sites in the
      promoter were reported to be important for the serum and TPA inducibility of the
      vimentin gene. However, we find that the AP1 elements only contribute in part to
      c-Jun activation. Moreover, this activation can be duplicated in COS-1 or S2
      cells by expression of c-Jun or TAM67, and is dependent only on the leucine
      zipper region of c-Jun. Transient transfection analyses, electrophoretic mobility
      shift assays, DNA precipitation assays, and coimmunoprecipitation studies suggest
      that c-Jun is able to synergize with the activator protein Sp1 in binding to GC
      box1 to enhance vimentin gene expression.

PMID- 14654786
TI  - Resetting the histone code at CDKN2A in HNSCC by inhibition of DNA methylation.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the fifth most frequent cancer
      in the US. Several genetic and epigenetic alterations are associated with HNSCC
      tumorigenesis, including inactivation of CDKN2A, which encodes the p16 tumor
      suppressor, in cell lines and primary tumors by DNA methylation. Reactivation of
      tumor suppressor genes by DNA-demethylating agents and histone deacetylase (HDAC)
      inhibitors shows therapeutic promise for other cancers. Therefore, we
      investigated the ability of these agents to reactivate p16 in Tu159 HNSCC cells.
      Treatment of cells with 5-aza-2'deoxycytidine (5-aza-dC) increases CDKN2A
      expression and slightly increases histone H3 acetylation at this gene. No
      reactivation of CDKN2A is observed upon treatment with the HDAC inhibitor
      trichostatin A (TSA), but synergistic reactivation of CDKN2A is observed upon
      sequential treatment of Tu159 cells with both 5-aza-dC and TSA. Silencing of
      CDKN2A in Tu159 cells is correlated with increased methylation of histone H3 at
      lysine 9 and decreased methylation at lysine 4 relative to the upstream p15 gene
      promoter. Interestingly, global levels of H3-K9 methylation are decreased upon
      treatment with 5-aza-dC. Together these data indicate that DNA methylation is a
      dominant epigenetic mark for silencing of CDKN2A in Tu159 tumor cells. Moreover,
      changes in DNA methylation can reset the histone code by impacting multiple H3
      modifications.

PMID- 14654787
TI  - Segregation of NF-kappaB activation through NEMO/IKKgamma by Tax and TNFalpha:
      implications for stimulus-specific interruption of oncogenic signaling.
AB  - Nuclear factor-kappaB essential modulator (NEMO), also called IKKgamma, has been
      proposed as a 'universal' adaptor of the I-kappaB kinase (IKK) complex for
      stimuli such as proinflammatory cytokines, microbes, and the HTLV-I Tax
      oncoprotein. Currently, it remains unclear whether the many signals that activate
      NF-kappaB through NEMO converge identically or differently. We have adopted two
      approaches to answer this question. First, we generated and targeted
      intracellularly three NEMO-specific monoclonal antibodies (mAbs). These mAbs
      produced two distinct intracellular NF-kappaB inhibition profiles segregating
      TNFalpha from Tax activation. Second, using NEMO knockout mouse fibroblasts and
      10 NEMO mutants, we found that different regions function in trans either to
      complement or to inhibit dominantly TNFalpha, IL-1beta, or Tax activation of NF
      kappaB. For instance, NEMO (1-245 amino acids) supported Tax-mediated NF-kappaB
      activation, but did not serve TNFalpha- or IL-1beta signaling. Altogether, our
      findings indicate that while NEMO 'universally' adapts numerous NF-kappaB
      activators, it may do so through separable domains. We provide the first evidence
      that selective targeting of NEMO can abrogate oncogenic Tax signaling without
      affecting signals used for normal cellular metabolism.

PMID- 14654788
TI  - Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer
      cells.
AB  - Two paclitaxel(Ptx)-resistant ovarian cancer cell lines, 1A9/Ptx-10 and 1A9/Ptx
      22, isolated from the 1A9 cell line (a clone of the A2780 line) by continuous
      exposure to Ptx and verapamil, have point mutations in their major beta-tubulin
      gene and in one or both alleles of their TP53 gene. These cells were examined for
      alterations in cell cycle regulators and the tubulin-binding protein stathmin.
      Unlike parental cells, neither 1A9/Ptx-10 nor 1A9/Ptx-22 expressed detectable
      levels of p21(WAF1/Cip1), a putative transcriptional regulator of stathmin, but
      did overexpress stathmin and Bcl2. No differences were noted in the expression
      levels of proliferative cell nuclear antigen or tyrosine-phosphorylated p34Cdc2.
      Ptx treatment altered little the expression of stathmin in the parental cell
      line, although it increased p21(WAF1/Cip1) levels several-fold. Infection of Ptx
      resistant lines with a wild-type TP53-bearing adenovirus (AdWTp53) changed cell
      cycle distribution and increased the levels of p21(WAF1/Cip1), but caused no
      changes in stathmin levels. Microtubule drug resistance in ovarian carcinoma may
      be associated with altered p53/21(WAF1/Cip1) regulatory pathways for stathmin
      expression and function.

PMID- 14654789
TI  - A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved
      in the p53-mediated apoptosis pathway.
AB  - We identified IFI16 as a BRCA1-associated protein involved in p53-mediated
      apoptosis. IFI16 contains the Pyrin/PAAD/DAPIN domain, commonly found in cell
      death-associated proteins. BRCA1 (aa 502-802) interacted with the IFI16 Pyrin
      domain (aa 1-130). We found that IFI16 was localized in the nucleoplasm and
      nucleoli. Clear nucleolar IFI16 localization was not observed in HCC1937 BRCA1
      mutant cells, but reintroduction of wild-type BRCA1 restored IFI16 nuclear
      relocalization following IR (ionizing radiation). Coexpression of IFI16 and BRCA1
      enhanced DNA damage-induced apoptosis in mouse embryonic fibroblasts from BRCA1
      mutant mice expressing wild-type p53, although mutant IFI16 deficient in binding
      to BRCA1 did not induce apoptosis. Furthermore, tetracycline-induced IFI16
      collaborated in inducing apoptosis when adenovirus p53 was expressed in DNA
      damaged p53-deficient EJ cells. These results indicate a BRCA1-IFI16 role in p53
      mediated transmission of DNA damage signals and apoptosis.

PMID- 14654790
TI  - PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic
      tumour cells.
AB  - Loss of growth control and a marked resistance to apoptosis are considered major
      mechanisms driving tumour progression. Protein kinases C (PKC) have been shown to
      be important in the regulation of proliferation and apoptosis. In this report, we
      investigated the role of the PKC-like kinase PKCmu in the control of these
      processes in pancreatic adenocarcinoma cells. We demonstrate that in these cells,
      PKCmu expression strongly correlates with resistance to CD95-induced apoptosis.
      Inhibition of PKCmu with Goe6983 sensitized resistant cells to CD95-induced
      apoptosis. In CD95-sensitive Colo357 cells, forced overexpression of PKCmu
      strongly reduced CD95-mediated apoptosis, an effect that could be reversed by
      pretreatment with Goe6983. In addition, PKCmu overexpression led to a strongly
      enhanced cell growth and to a significant increase of telomerase activity. In an
      attempt to identify the signalling pathways affected by PKCmu, we identified the
      antiapoptotic proteins c-FLIPL and survivin to be strongly upregulated in PKCmu
      overexpressing cells. Immunohistochemical analysis of pancreatic tumour tissue of
      48 patients and 10 normal pancreatic tissues revealed marked overexpression of
      PKCmu in tumours. In conclusion, we showed that PKCmu controls proliferative, as
      well as anti-apoptotic, signalling pathways and therefore plays an important role
      in acquiring the malignant phenotype of pancreatic tumours.

PMID- 14654791
TI  - Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is
      associated with cyclin D1 and hypoxia-inducible factor-1alpha (HIF-1alpha).
AB  - B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse
      embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1
      overexpression is a common phenomenon in different cancers, BCL-6 protein
      overexpression may not be restricted to lymphomas. In this study, expression of
      BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens
      from 150 breast cancer patients and 10 specimens of normal breast tissue. The
      results showed BCL-6 overexpression (> or =10% of cells) in 24/150 (16%) breast
      cancer patients, whereas in normal breast low expression (<1%) of BCL-6 was
      observed. In linear regression analysis BCL-6 expression was associated with
      cyclin D1 (r=0.197, P=0.016). Further, in chi2 analyses, BCL-6-positivity was
      associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor
      1alpha (P<0.001). Involvement of BCL-6 in breast carcinogenesis is further
      underscored by comparative genomic hybridization analysis that showed gains at
      the BCL-6 locus (3q27) in 14/86 (16%) breast cancer tissues. The cases with
      amplification in BCL-6 showed an increased (25%) incidence of BCL-6 protein
      overexpression. Thus, this study is the first to show that BCL-6 oncogene
      activation plays a role in cancers other than lymphomas.

PMID- 14654792
TI  - Repression of mRNA for the PLK cell cycle gene after DNA damage requires BRCA1.
AB  - DNA damage activates the G2 cell cycle checkpoint to allow time for DNA repair
      before mitotic entry. The mechanism involves inhibition of the enzymatic activity
      for polo-like kinase 1 (Plk1), rendering Cdc25C with a basal phosphatase activity
      that is insufficient for converting Cdc2 to the fully active G2/M transition
      kinase. We found that cell cycle arrest at the G2/M boundary after ionizing
      radiation (IR) of breast carcinoma cells may involve repression of the gene for
      Plk1, PLK, mediated by the tumor-suppressor protein BRCA1. The p53-defective MT-1
      cell line had an apparent accumulation of G2/M phase cells 12 h after
      irradiation. This response was preceded by a transient downregulation of PLK mRNA
      expression with a barely detectable level 6 h after exposure to IR but recovered
      after 12 h. A significantly lower fraction of irradiated BRCA1(-/-) HCC1937 cells
      arrested in the G2/M phase after 12 h, and the transient response of PLK mRNA was
      also considerably impaired. After reconstitution of wild-type BRCA1 in the
      HCC1937 cells however, downregulation of PLK mRNA as well as Plk1 protein
      expression after IR was restored. Moreover, the suppression of PLK mRNA
      expression 6 h after irradiation was completely abolished by the specific CHEK1
      kinase inhibitor UCN-01, further indicating that the effector mechanism of DNA
      damage on PLK signals through BRCA1 and its downstream CHEK1. Our observations
      provide new information about the diversity of regulatory mechanisms governed by
      BRCA1 in DNA damage checkpoint control.

PMID- 14654793
TI  - Chfr inactivation is not associated to chromosomal instability in colon cancers.
AB  - Numerous observations suggest that chromosome instability is caused by mitotic
      abnormalities such as errors in the partitioning of chromosomes. Chfr was
      recently defined as a central component of a new mitotic checkpoint that delays
      chromosome condensation in response to mitotic stress. Chfr was shown to be
      frequently inactivated in several human neoplasms, including colon, lung and
      esophageal cancers. To test whether Chfr inactivation may lead or participate to
      chromosomal instability (CIN), we analysed the genetic and epigenetic status of
      the gene in a large panel of primary colon and breast cancers, as well as in
      colon and breast cancer cell lines displaying either a microsatellite instability
      or a CIN. Our results confirm that Chfr is frequently inactivated in colon
      cancers, through a mechanism of hypermethylation of the promoter sequences. In
      contrast, the loss of Chfr expression appears to be a rare event in breast
      cancers. Furthermore, our data demonstrate that Chfr inactivation is not
      associated with CIN in these frequent types of human cancers.

PMID- 14654794
TI  - Paediatric clinical trials: redressing the imbalance.

PMID- 14654795
TI  - Tissue microarrays in drug discovery.

PMID- 14654796
TI  - Glia: a novel drug discovery target for clinical pain.

PMID- 14654797
TI  - Neuropeptide gene polymorphisms and human behavioural disorders.

PMID- 14654798
TI  - Opportunities in somatostatin research: biological, chemical and therapeutic
      aspects.

PMID- 14654799
TI  - Metabolic engineering for drug discovery and development.

PMID- 14654800
TI  - Science needs the commission, Sturm und Drang and all.

PMID- 14654801
TI  - France and Japan lock horns in battle to host research reactor.

PMID- 14654802
TI  - Shortcomings halt study of Swiss cancer vaccine.

PMID- 14654803
TI  - Iraqis draw up blueprint for revitalized science academy.

PMID- 14654804
TI  - Ship row flags up funding of war in Africa.

PMID- 14654805
TI  - Budget cuts force Hong Kong to reduce salaries.

PMID- 14654806
TI  - Climate study highlights inadequacy of emissions cuts.

PMID- 14654807
TI  - Scientists go to jail to crack substance abuse.

PMID- 14654808
TI  - Rapid drug trial offers hope to CJD patients.

PMID- 14654809
TI  - Europe eyes merit-based agency.

PMID- 14654811
TI  - Developmental reprogramming: take a cell, any cell.

PMID- 14654812
TI  - Ocean drilling: digging in.

PMID- 14654813
TI  - Citation rate unrelated to journals' impact factors.

PMID- 14654814
TI  - GM-debate methodology works in the real world.

PMID- 14654815
TI  - Is science losing out in the race for recognition?

PMID- 14654821
TI  - Developmental biology: long-range signalling by touch.

PMID- 14654823
TI  - Astrophysics: testing time for gravity.

PMID- 14654825
TI  - Chemistry: internal combustion.

PMID- 14654824
TI  - Membrane trafficking: coat control by curvature.

PMID- 14654827
TI  - Condensed-matter physics: illuminating behaviour.

PMID- 14654826
TI  - Mammalian evolution: isolationist tendencies.

PMID- 14654828
TI  - Medicine: taking apart a cancer protein.

PMID- 14654830
TI  - On-chip manipulation of free droplets.

PMID- 14654831
TI  - Palaeontology: a polydactylous amniote from the Triassic period.

PMID- 14654832
TI  - TRP channels as cellular sensors.
AB  - TRP channels are the vanguard of our sensory systems, responding to temperature,
      touch, pain, osmolarity, pheromones, taste and other stimuli. But their role is
      much broader than classical sensory transduction. They are an ancient sensory
      apparatus for the cell, not just the multicellular organism, and they have been
      adapted to respond to all manner of stimuli, from both within and outside the
      cell.

PMID- 14654833
TI  - Structural snapshots of the mechanism and inhibition of a guanine nucleotide
      exchange factor.
AB  - Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide exchange
      stimulated by guanine nucleotide exchange factors (GEFs). Nucleotide dissociation
      from small G protein-GEF complexes involves transient GDP-bound intermediates
      whose structures have never been described. In the case of Arf proteins, small G
      proteins that regulate membrane traffic in eukaryotic cells, such intermediates
      can be trapped either by the natural inhibitor brefeldin A or by charge reversal
      at the catalytic glutamate of the Sec7 domain of their GEFs. Here we report the
      crystal structures of these intermediates that show that membrane recruitment of
      Arf and nucleotide dissociation are separate reactions stimulated by Sec7. The
      reactions proceed through sequential rotations of the Arf.GDP core towards the
      Sec7 catalytic site, and are blocked by interfacial binding of brefeldin A and
      unproductive stabilization of GDP by charge reversal. The structural
      characteristics of the reaction and its modes of inhibition reveal unexplored
      ways in which to inhibit the activation of small G proteins.

PMID- 14654834
TI  - An increased estimate of the merger rate of double neutron stars from
      observations of a highly relativistic system.
AB  - The merger of close binary systems containing two neutron stars should produce a
      burst of gravitational waves, as predicted by the theory of general relativity. A
      reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial
      in order to predict whether current gravity wave detectors will be successful in
      detecting such bursts. Present estimates of this rate are rather low, because we
      know of only a few double-neutron-star binaries with merger times less than the
      age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737
      3039, which is a member of a highly relativistic double-neutron-star binary with
      an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time
      much shorter than for any other known neutron-star binary. Together with the
      relatively low radio luminosity of PSR J0737-3039, this timescale implies an
      order-of-magnitude increase in the predicted merger rate for double-neutron-star
      systems in our Galaxy (and in the rest of the Universe).

PMID- 14654835
TI  - Continuous magnetic reconnection at Earth's magnetopause.
AB  - The most important process that allows solar-wind plasma to cross the
      magnetopause and enter Earth's magnetosphere is the merging between solar-wind
      and terrestrial magnetic fields of opposite sense-magnetic reconnection. It is at
      present not known whether reconnection can happen in a continuous fashion or
      whether it is always intermittent. Solar flares and magnetospheric substorms--two
      phenomena believed to be initiated by reconnection--are highly burst-like
      occurrences, raising the possibility that the reconnection process is
      intrinsically intermittent, storing and releasing magnetic energy in an explosive
      and uncontrolled manner. Here we show that reconnection at Earth's high-latitude
      magnetopause is driven directly by the solar wind, and can be continuous and even
      quasi-steady over an extended period of time. The dayside proton auroral spot in
      the ionosphere--the remote signature of high-latitude magnetopause reconnection-
      is present continuously for many hours. We infer that reconnection is not
      intrinsically intermittent; its steadiness depends on the way that the process is
      driven.

PMID- 14654836
TI  - Direct observation of Tomonaga-Luttinger-liquid state in carbon nanotubes at low
      temperatures.
AB  - The electronic transport properties of conventional three-dimensional metals are
      successfully described by Fermi-liquid theory. But when the dimensionality of
      such a system is reduced to one, the Fermi-liquid state becomes unstable to
      Coulomb interactions, and the conduction electrons should instead behave
      according to Tomonaga-Luttinger-liquid (TLL) theory. Such a state reveals itself
      through interaction-dependent anomalous exponents in the correlation functions,
      density of states and momentum distribution of the electrons. Metallic single
      walled carbon nanotubes (SWNTs) are considered to be ideal one-dimensional
      systems for realizing TLL states. Indeed, the results of transport measurements
      on metal-SWNT and SWNT-SWNT junctions have been attributed to the effects of
      tunnelling into or between TLLs, although there remains some ambiguity in these
      interpretations. Direct observations of the electronic states in SWNTs are
      therefore needed to resolve these uncertainties. Here we report angle-integrated
      photoemission measurements of SWNTs. Our results reveal an oscillation in the pi
      electron density of states owing to one-dimensional van Hove singularities,
      confirming the one-dimensional nature of the valence band. The spectral function
      and intensities at the Fermi level both exhibit power-law behaviour (with almost
      identical exponents) in good agreement with theoretical predictions for the TLL
      state in SWNTs.

PMID- 14654837
TI  - Migration of seismic scatterers associated with the 1993 Parkfield aseismic
      transient event.
AB  - The time-varying deformation field within a fault zone, particularly at depths
      where earthquakes occur, is important for understanding fault behaviour and its
      relation to earthquake occurrence. But detection of this temporal variation has
      been extremely difficult, although laboratory studies have long suggested that
      certain structural changes, such as the properties of crustal fractures, should
      be seismically detectable. Here we present evidence that such structural changes
      are indeed observable. In particular, we find a systematic temporal variation in
      the seismograms of repeat microearthquakes that occurred on the Parkfield segment
      of the San Andreas fault over the decade 1987-97. Our analysis reveals a change
      of the order of 10 m in the location of scatterers which plausibly lie within the
      fault zone at a depth of approximately 3 km. The motion of the scatterers is
      coincident, in space and time, with the onset of a well documented aseismic
      transient (deformation event). We speculate that this structural change is the
      result of a stress-induced redistribution of fluids in fluid-filled fractures
      caused by the transient event.

PMID- 14654838
TI  - Oligocene mammals from Ethiopia and faunal exchange between Afro-Arabia and
      Eurasia.
AB  - Afro-Arabian mammalian communities underwent a marked transition near the
      Oligocene/Miocene boundary at approximately 24 million years (Myr) ago. Although
      it is well documented that the endemic paenungulate taxa were replaced by
      migrants from the Northern Hemisphere, the timing and evolutionary dynamics of
      this transition have long been a mystery because faunas from about 32 to 24 Myr
      ago are largely unknown. Here we report a late Oligocene fossil assemblage from
      Ethiopia, which constrains the migration to postdate 27 Myr ago, and yields new
      insight into the indigenous faunal dynamics that preceded this event. The fauna
      is composed of large paenungulate herbivores and reveals not only which earlier
      taxa persisted into the late Oligocene epoch but also demonstrates that one
      group, the Proboscidea, underwent a marked diversification. When Eurasian
      immigrants entered Afro-Arabia, a pattern of winners and losers among the
      endemics emerged: less diverse taxa such as arsinoitheres became extinct,
      moderately species-rich groups such as hyracoids continued into the Miocene with
      reduced diversity, whereas the proboscideans successfully carried their adaptive
      radiation out of Afro-Arabia and across the world.

PMID- 14654839
TI  - Ocean currents mediate evolution in island lizards.
AB  - Islands are considered to be natural laboratories in which to examine evolution
      because of the implicit assumption that limited gene flow allows tests of
      evolutionary processes in isolated replicates. Here we show that this well
      accepted idea requires re-examination. Island inundation during hurricanes can
      have devastating effects on lizard populations in the Bahamas. After severe
      storms, islands may be recolonized by over-water dispersal of lizards from
      neighbouring islands. High levels of gene flow may homogenize genes responsible
      for divergence, and are widely viewed as a constraining force on evolution.
      Ultimately, the magnitude of gene flow determines the extent to which populations
      diverge from one another, and whether or not they eventually form new species. We
      show that patterns of gene flow among island populations of Anolis lizards are
      best explained by prevailing ocean currents, and that over-water dispersal has
      evolutionary consequences. Across islands, divergence in fitness-related
      morphology decreases with increasing gene flow. Results suggest that over-water
      dispersal after hurricanes constrains adaptive diversification in Anolis lizards,
      and that it may have an important but previously undocumented role in this
      classical example of adaptive radiation.

PMID- 14654840
TI  - Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila.
AB  - Drosophila thoracic mechanosensory bristles originate from cells that are singled
      out from 'proneural' groups of competent epithelial cells. Neural competence is
      restricted to individual sensory organ precursors (SOPs) by Delta/Notch-mediated
      'lateral inhibition', whereas other cells in the proneural field adopt an
      epidermal fate. The precursors of the large macrochaetes differentiate separately
      from individual proneural clusters that comprise about 20-30 cells or as
      heterochronic pairs from groups of more than 100 cells, whereas the precursors of
      the small regularly spaced microchaetes emerge from even larger proneural fields.
      This indicates that lateral inhibition might act over several cell diameters; it
      was difficult to reconcile with the fact that the inhibitory ligand Delta is
      membrane-bound until the observation that SOPs frequently extend thin processes
      offered an attractive hypothesis. Here we show that the extension of these planar
      filopodia--a common attribute of wing imaginal disc cells--is promoted by Delta
      and that their experimental suppression reduces Notch signalling in distant cells
      and increases bristle density in large proneural groups, showing that these
      membrane specializations mediate long-range lateral inhibition.

PMID- 14654841
TI  - Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer
      curvature.
AB  - Protein coats deform flat lipid membranes into buds and capture membrane proteins
      to form transport vesicles. The assembly/disassembly cycle of the COPI coat on
      Golgi membranes is coupled to the GTP/GDP cycle of the small G protein Arf1. At
      the heart of this coupling is the specific interaction of membrane-bound Arf1-GTP
      with coatomer, a complex of seven proteins that forms the building unit of the
      COPI coat. Although COPI coat disassembly requires the catalysis of GTP
      hydrolysis in Arf1 by a specific GTPase-activating protein (ArfGAP1), the precise
      timing of this reaction during COPI vesicle formation is not known. Using time
      resolved assays for COPI dynamics on liposomes of controlled size, we show that
      the rate of ArfGAP1-catalysed GTP hydrolysis in Arf1 and the rate of COPI
      disassembly increase over two orders of magnitude as the curvature of the lipid
      bilayer increases and approaches that of a typical transport vesicle. This leads
      to a model for COPI dynamics in which GTP hydrolysis in Arf1 is organized
      temporally and spatially according to the changes in lipid packing induced by the
      coat.

PMID- 14654842
TI  - Targeted degradation of TOC1 by ZTL modulates circadian function in Arabidopsis
      thaliana.
AB  - The underlying mechanism of circadian rhythmicity appears to be conserved among
      organisms, and is based on negative transcriptional feedback loops forming a
      cellular oscillator (or 'clock'). Circadian changes in protein stability,
      phosphorylation and subcellular localization also contribute to the generation
      and maintenance of this clock. In plants, several genes have been shown to be
      closely associated with the circadian system. However, the molecular mechanisms
      proposed to regulate the plant clock are mostly based on regulation at the
      transcriptional level. Here we provide genetic and molecular evidence for a role
      of ZEITLUPE (ZTL) in the targeted degradation of TIMING OF CAB EXPRESSION 1
      (TOC1) in Arabidopsis thaliana (thale cress). The physical interaction of TOC1
      with ZTL is abolished by the ztl-1 mutation, resulting in constitutive levels of
      TOC1 protein expression. The dark-dependent degradation of TOC1 protein requires
      functional ZTL, and is prevented by inhibiting the proteosome pathway. Our
      results show that the TOC1-ZTL interaction is important in the control of TOC1
      protein stability, and is probably responsible for the regulation of circadian
      period by the clock.

PMID- 14654843
TI  - Proteomic characterization of the human centrosome by protein correlation
      profiling.
AB  - The centrosome is the major microtubule-organizing centre of animal cells and
      through its influence on the cytoskeleton is involved in cell shape, polarity and
      motility. It also has a crucial function in cell division because it determines
      the poles of the mitotic spindle that segregates duplicated chromosomes between
      dividing cells. Despite the importance of this organelle to cell biology and more
      than 100 years of study, many aspects of its function remain enigmatic and its
      structure and composition are still largely unknown. We performed a mass
      spectrometry-based proteomic analysis of human centrosomes in the interphase of
      the cell cycle by quantitatively profiling hundreds of proteins across several
      centrifugation fractions. True centrosomal proteins were revealed by both
      correlation with already known centrosomal proteins and in vivo localization. We
      identified and validated 23 novel components and identified 41 likely candidates
      as well as the vast majority of the known centrosomal proteins in a large
      background of nonspecific proteins. Protein correlation profiling permits the
      analysis of any multiprotein complex that can be enriched by fractionation but
      not purified to homogeneity.

PMID- 14654845
TI  - Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly.
AB  - The assembly of 80S ribosomes requires joining of the 40S and 60S subunits, which
      is triggered by the formation of an initiation complex on the 40S subunit. This
      event is rate-limiting for translation, and depends on external stimuli and the
      status of the cell. Here we show that 60S subunits are activated by release of
      eIF6 (also termed p27BBP). In the cytoplasm, eIF6 is bound to free 60S but not to
      80S. Furthermore, eIF6 interacts in the cytoplasm with RACK1, a receptor for
      activated protein kinase C (PKC). RACK1 is a major component of translating
      ribosomes, which harbour significant amounts of PKC. Loading 60S subunits with
      eIF6 caused a dose-dependent translational block and impairment of 80S formation,
      which were reversed by expression of RACK1 and stimulation of PKC in vivo and in
      vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine
      residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational
      rescue. We propose that eIF6 release regulates subunit joining, and that RACK1
      provides a physical and functional link between PKC signalling and ribosome
      activation.

PMID- 14654853
TI  - Young scientist: women mentoring women.

PMID- 14654844
TI  - Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2.
AB  - Feedback inhibition is a fundamental principle in signal transduction allowing
      rapid adaptation to different stimuli. In mammalian cells, the major feedback
      inhibitor for G-protein-coupled receptors (GPCR) is G-protein-coupled receptor
      kinase 2 (GRK-2), which phosphorylates activated receptors, uncouples them from G
      proteins and initiates their internalization. The functions of GRK-2 are
      indispensable and need to be tightly controlled. Dysregulation promotes disorders
      such as hypertension or heart failure. In our search for a control mechanism for
      this vital kinase, here we show that the Raf kinase inhibitor protein (RKIP) is a
      physiological inhibitor of GRK-2. After stimulation of GPCR, RKIP dissociates
      from its known target, Raf-1 (refs 6-8), to associate with GRK-2 and block its
      activity. This switch is triggered by protein kinase C (PKC)-dependent
      phosphorylation of the RKIP on serine 153. The data delineate a new principle in
      signal transduction: by activating PKC, the incoming receptor signal is enhanced
      both by removing an inhibitor from Raf-1 and by blocking receptor
      internalization. A physiological role for this mechanism is shown in
      cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic
      signalling and contractile activity.

PMID- 14654854
TI  - Nuts and bolts.

PMID- 14654856
TI  - Getting to grips with severe personality disorder.

PMID- 14654857
TI  - Does personality change and, if so, what changes?
AB  - BACKGROUND: Although the question of whether or not personality changes is
      fundamental to much of what clinicians do, we do not appear to be very curious
      about the question itself. METHOD: This paper considers three separate but
      related issues: (a) Does personality change? (b) If it does, then what changes?
      (c) How can we show that change has taken place? Costa and McCrea have produced a
      model of personality that helps to answer (a) and (b), as it distinguishes 'Basic
      Tendencies' from 'Characteristic Adaptations'. The former are largely innate,
      fixed dispositions that produce the latter (which are highly variable) depending
      on its interaction with differing environments. Thus, personality is both static
      and dynamic depending on its definition. It will also be argued that detecting
      change is complex as there are many alternative definitions of the relevant
      outcome variable. Moreover, measuring several different outcomes does not help as
      change in one measure is often not matched by a concordant change in another.
      Some practical examples are provided to support this position. CONCLUSIONS: In
      the absence of a firm theoretical base, the author believes that only limited
      conclusions can be drawn about the efficacy of treatment in personality disorder.

PMID- 14654858
TI  - Severe personality disorder emerging in childhood: a proposal for a new
      developmental disorder.
AB  - BACKGROUND: The concept of 'severe personality disorder' is currently applied to
      adults with a history of serious antisocial and offending behaviour. There is,
      however, no similar classification that can be applied to the sub-group of
      children and adolescents who display persistent and serious offending from an
      early age. This omission from diagnostic nomenclature prevents the appropriate
      early identification, assessment and management of these young people. METHOD:
      This paper therefore proposes a new developmental disorder: 'severe personality
      disorder emerging in childhood'. The existing evidence base strongly supports the
      presence of a developmental trajectory from childhood to adult life for the small
      number of children who show early signs of severe personality disorder (SPD).
      Based on a review of the literature and the experience of working in a
      specialist, forensic Child and Adolescent Mental Health Service (CAMHS), a multi
      factorial model is proposed that outlines the developmental trajectory of SPD.
      This model includes neurobiological, psychosocial, environmental and systemic
      factors, within a developmental framework, and contributes to a more
      developmentally appropriate understanding of the genesis of severe personality
      disorder.

PMID- 14654859
TI  - Motivating factors for male forensic patients with personality disorder.
AB  - INTRODUCTION: Treatability is currently a crucial component for detention under
      the Mental Health Act (England and Wales) for the Psychopathic Disorder
      (personality disorder) classification and there is continuing debate about the
      nature and assessment of treatability of individuals with personality disorder.
      Previous research has identified motivation to engage in treatment as a
      significant factor in the assessment of treatability; however, motivation is not
      a static predictor but a state of readiness or eagerness to change, which may
      fluctuate from one time or situation to another. While previous studies have
      explored factors within the individual that are used to assess treatability, this
      study aims to explore what, if any, aspects of an inpatient forensic setting
      influence patients' motivation to engage in treatment. METHOD: The study examines
      patients' experiences of engaging in treatment in an inpatient forensic
      Personality Disorder Directorate using a qualitative approach to identify
      possible service-, ward- and therapist-level influences on patients' motivation
      to engage. RESULTS: Preliminary categories were identified across the data,
      including: support, treatment, safety, external belief, belonging, internal
      motivation and therapeutic relationship. CONCLUSIONS: Implications for the
      service are identified and areas for further qualitative exploration are
      highlighted.

PMID- 14654860
TI  - Neurobiological substrates of antisocial and borderline personality disorder:
      preliminary results of a functional fMRI study.
AB  - BACKGROUND: Neuropsychological and imaging studies of patients with antisocial
      (ASPD) and borderline personality disorder (BPD) are suggestive of frontal lobe
      dysfunction in these individuals. In normal subjects functional brain imaging has
      been used to investigate the neuroanatomy of impulse control. There are no such
      imaging studies in personality-disordered populations. AIM: This study aimed to
      investigate which neuronal networks are involved in response inhibition in
      Cluster B personality disorders and whether these are different from healthy
      subjects. HYPOTHESIS: We hypothesized that the personality-disordered sample
      would have attenuated orbitofrontal cortex responses during performance of a
      Go/NoGo task compared with healthy controls. METHOD: Eight inpatients with a DSM
      IV diagnosis of borderline or antisocial personality disorder and eight healthy
      controls were scanned using fMRI while performing a Go/NoGo task. Impulsivity was
      assessed using the Barratt Impulsivity Scale (BIS) and the Impulsiveness
      Venturesomeness-Empathy (IVE) inventory. RESULTS: In the control group the main
      focus of activation during response inhibition was in the prefrontal cortex,
      specifically the right dorsolateral and the left orbitofrontal cortex. Active
      regions in the patient group showed a more bilateral and extended pattern of
      activation across the medial, superior and inferior frontal gyri extending to the
      anterior cingulate. CONCLUSIONS: fMRI is a useful tool to detect brain activation
      during response inhibition. ASPD and BPD patients activate different neural
      networks to successfully inhibit pre-potent responses.

PMID- 14654861
TI  - Editorial: new forensic mental health law in Japan.

PMID- 14654862
TI  - Patterns of self-harm and attempted suicide among white and black/mixed race
      female prisoners.
AB  - AIM: The aim was to investigate ethnic differences in lifetime self-harm and
      attempted suicide in women prisoners, and to examine relationships between self
      harm, suicide and substance use on dependence. BACKGROUND: Previous studies have
      suggested that there may be ethnic differences in the proportion of prisoners
      reporting substance misuse, self-harm and attempted suicide, although relatively
      few minority ethnic women have been studied in the UK. This study examines drug
      and alcohol dependence in white and black British women in prison, and explores
      possible associations with self-harm, suicide attempts, and family violence.
      METHODS: 301 women (190 white, 111 black or mixed race) were interviewed in ten
      prisons from different parts of England. Measures included the Alcohol Use
      Disorders Identification test (AUDIT), the severity of Dependence Scale (SDS),
      and section C (suicidality) of the MINI International Neuropsychiatric Interview.
      RESULTS: Half of the women in the sample reported at least one act of self-harm
      in their life and 46% reported making a suicide attempt at some time. Lifetime
      self-harm was associated with a history of harmful drinking and with being a
      victim of violence, including physical assault, sexual assault and violence from
      family and friends. Lifetime suicide attempts were associated with reported
      violence from family or friends. Current high suicide risk was most common among
      women on remand. Drug dependence and reported violence from family or friends
      were both more common amongst white women than black/mixed race women. Self-harm
      and attempted suicide were generally more common among white women, but
      black/mixed race women dependent on drugs had the highest proportion of women
      reporting self-harm. There was tentative support for a three-way association
      between ethnicity, dependence and self-harm; this raises the possibility that
      drug dependence may be a predictor of self-harm in the black female prison
      population.

PMID- 14654863
TI  - Searching for a developmental typology of personality and its relations to
      antisocial behaviour: a longitudinal study of an adjudicated men sample.
AB  - The search for an empirically based personality typology has regained the
      interest of researchers. To date, however, empirical inquiries have mainly been
      cross-sectional. In this study, an empirically based developmental typology of
      personality was identified using data from a prospective longitudinal study of a
      sample of men adjudicated during their adolescence and assessed on four occasions
      until midlife. Cluster analyses were performed on measures of disinhibition,
      negative emotionality, and extraversion. Four developmental types of personality
      were identified. The first was characterized by average scores in the three
      traits in adolescence that decreased linearly until midlife (39%). The second
      type displayed very high scores in disinhibition and negative emotionality in
      adolescence that decreased rapidly during early adulthood (24%). The third type
      was characterized by very high scores in disinhibition and negative emotionality
      that remained stable until midlife, while extraversion was average during
      adolescence and then decreased rapidly until midlife (17%). The fourth type was
      characterized by high scores in disinhibition and negative emotionality in
      adolescence that was followed by cycles of decreases and increases until midlife
      (20%). These four developmental types of personality seemed to be related to
      known antisocial behaviour trajectories.

PMID- 14654864
TI  - Children admitted to high security (special) hospital.
AB  - INTRODUCTION: The Special Hospitals in England provide psychiatric treatment in
      high security. The aim of this study was to examine the demographics and
      background characteristics of children admitted to high security hospitals in
      England, using the special hospital case register. METHOD: Forty-six children
      (the subject group) were admitted to a high security hospital under the MHA
      (1983) classification of disorder of mental illness and/or psychopathic disorder
      between 1983 and 1999, 33 (72%) of whom were male. A comparison group of adults
      was matched on sex, legal classification of detention and MHA 1983 classification
      of disorder. RESULTS: The children were admitted for a similar range of offences
      to those of the comparison group. However, the children had received convictions
      for criminal damage and violence at a significantly earlier age, they were more
      likely to have experienced a change in caregiver during their childhood, been
      placed in a children's home and were less likely to be living with a family
      member on their 16th birthday. Children admitted to special hospital experience a
      lot of disruption in their childhood and are extremely high users of multi-agency
      services as they grow up. DISCUSSION: Issues are raised regarding how to provide
      a developmentally sensitive service for children who require high security care.

PMID- 14654865
TI  - Childhood behaviour as related to subsequent drinking offences and violent
      offending: a prospective study of 11- to 14-year-old youths into their fourth
      decade.
AB  - BACKGROUND: Childhood hyperactivity has previously been found to be closely
      connected to subsequent alcohol problems and violent offending among men
      considered to be without major mental disorders. For others, these associations
      might be moderated or confounded by other factors, predominantly comorbid conduct
      disorder. AIMS: The purpose of the study was to investigate aspects of childhood
      hyperactive behaviour in relation to alcohol or violent offences in adult life,
      taking the possible confounders of early criminality and aggressive behaviour
      into account. Method A total of 192 young male law breakers and 95 non-criminal
      controls were followed from age 11-14 years into their thirties. Information on
      aspects of hyperactivity, aggressive behaviour, early criminality and later
      offences was included in the analyses. RESULTS: The results supported the
      hypothesis that aspects of childhood hyperactive behaviour were significantly
      associated with later drinking offences and violent offending. Further analyses
      revealed attention difficulties to be the component of hyperactivity most
      contributing to the relationship. When taking possible confounding variables into
      consideration, attention difficulties were related to subsequent violent
      offending among boys with early criminality, independently of early aggressive
      behaviour. Early criminality, attention difficulties and aggressive behaviour,
      however, often co-occurred in the same individual. Subsequent drinking offences
      or violent offending appeared seven times more often among individuals with all
      early behavioural problems as compared with those who had no such problems.
      CONCLUSION: Complex antisocial behaviours in adult life commonly represent
      persistence of complex childhood behavioural difficulties, but among young law
      breakers there does appear to be a subgroup of boys with a main problem of
      attention difficulties who go on to violent offending, even in the absence of
      early manifestation of aggression.

PMID- 14654866
TI  - Referred to high secure care: determinants of a bed offer/admission and placement
      after one year.
AB  - BACKGROUND: The admission process to high secure care ought to ensure that those
      admitted (a) receive mental health care that meets their needs and (b) that this
      is provided at an appropriate level of security. AIMS: A study was undertaken to
      test the effectiveness of the gate keeping process according to these two
      criteria. METHOD All referrals for admission to Rampton high security hospital
      over one year were examined and, in addition, all women, all Anglo-Caribbeans and
      a random 50% sample of the Caucasian male majority were selected for interview.
      Each case was followed up for 12 months following the panel decision to determine
      his/her placement at that time. RESULTS: Of 138 referred, 56 (41%) were initially
      offered a bed although nearly half (66) had been subsequently admitted by the end
      of the study period. Seriousness of mental disorder and offence were
      independently associated with admission. After one year, one third of those
      admitted were no longer in high secure care. CONCLUSIONS: The variables
      predictive of admission (i.e. seriousness of both mental disorder and offence)
      suggest that the decision-making process was valid. Placement at 12 months tended
      to endorse the decision not to offer a bed, but it is more difficult to interpret
      the reverse as short admissions to high security for those who left within 12
      months may have been appropriate. There was no apparent advantage in having a
      panel reviewing the decision of the assessing clinician.

PMID- 14654867
TI  - Invited editorial: A green-fingered approach can improve the clinical utility of
      violence risk assessment tools.

PMID- 14654868
TI  - Psychology brings justice: the science of forensic psychology.
AB  - In this paper the focus is on one aspect of forensic psychology: the development
      of psychological instruments, a social psychological model and assessment
      procedures for evaluating the credibility of witnesses and police detainees
      during interviewing. Clinically grounded case work and research has impacted on
      police interviewing and practice, the admissibility of expert psychological
      testimony and the outcome of cases of miscarriage of justice. After describing
      the research that laid the foundations for advancement of scientific knowledge in
      this area, a brief review is presented of 22 high-profile murder cases where
      convictions based on confession evidence have been quashed on appeal between 1989
      and 2001, often primarily on the basis of psychological evidence. The review of
      the cases demonstrates that psychological research and expert testimony in cases
      of disputed confessions have had a profound influence on the practice and ruling
      of the Court of Appeal for England and Wales and the British House of Lords. The
      cases presented in this paper show that it is wrong to assume that only persons
      with learning disability or those who are mentally ill make unreliable or false
      confessions. Personality factors, such as suggestibility, compliance, high trait
      anxiety and antisocial personality traits, are often important in rendering a
      confession unreliable. Future research needs to focus more on the role of
      personality factors in rendering the evidence of witnesses and suspects
      potentially unreliable.

PMID- 14654869
TI  - Mental health patients in criminal justice populations: needs, treatment and
      criminal behaviour.
AB  - BACKGROUND: Government policy requires that health and social care agencies work
      more closely together and in partnership with the criminal justice system. There
      is a well-established relationship between crime and mental disorder. METHOD: The
      Tracking Project provides for the first time in England the means of collating
      and analysing data on mental disorder (defined as receiving secondary care as
      patients of a Mental Health Trust) and crime (defined as all those charged with
      an offence). Data were collected over a three-year period for all individuals who
      had contact with the criminal justice system and mental health services in an
      English county. RESULTS: In a county population of 800,400, some 30,329 were
      offenders. More than a third had used a health or social care service during the
      three-year period; 8.0% were mentally disordered. Those offenders aged 25-64 and
      who contacted the police more than once were significantly more likely to be
      mentally disordered. Type of offence was also a relevant variable. The probation
      service showed broadly similar results. DISCUSSION: The research has provided for
      the first time substantive quantitative evidence of the relationship between
      crime and mental disorder. The results can be used as the basis for further work
      to target assessment and risk reduction measures at those most at risk.

PMID- 14654870
TI  - Predictive, concurrent, prospective and retrospective validity of self-reported
      delinquency.
AB  - BACKGROUND: The self-report method is widely used to measure offending. Previous
      studies suggest that it is generally valid, but that its validity may be lower
      for blacks than for whites. AIM To assess the validity of self-reported offending
      in relation to court referrals, and to investigate how it varies with types of
      offences, sex and race. METHOD: Annual court and self-report data were collected
      between ages 11 and 17 for eight offences in the Seattle Social Development
      Project, which is a prospective longitudinal survey of 808 youths. RESULTS: Self
      reports predicted future court referrals. Predictive validity was highest for
      drug offences, for males and for whites, and lowest for females and Asians. The
      probability of youths with a court referral reporting offences and arrests was
      highest for drug offences, for males, for whites and for blacks. Retrospective
      ages of onset agreed best with prospective ages for drug offences, Asians and
      whites. More Asians than blacks or whites failed retrospectively to report
      offences that had been reported prospectively. CONCLUSIONS: The validity of self
      reports of offending was high, especially for drug offences, for males and for
      whites. Contrary to prior research, validity was high for black males. It was
      lowest for Asian females. Sex and race differences in validity held up after
      controlling for socioeconomic status. Differential validity probability did not
      reflect police bias.

PMID- 14654871
TI  - Practice-based outcomes of dialectical behaviour therapy (DBT) targeting anger
      and violence, with male forensic patients: a pragmatic and non-contemporaneous
      comparison.
AB  - OBJECTIVE: To examine the effectiveness of an eighteen-month treatment based on
      dialectical behaviour therapy (DBT) targeting anger and violence, on a group of
      male forensic patients. METHOD: Eight male forensic patients in a high security
      hospital who met the criteria for borderline personality disorder measured by the
      Personality Assessment Inventory underwent 18 months of treatment. They completed
      three psychometric tests at pre-, mid- and post-treatment and at a six-month
      follow up. A comparison group (TAU) of nine patients, assessed as having similar
      personality disorders, received the usual treatment available in the hospital but
      excluding DBT. They completed the same tests at the same time intervals
      corresponding to the pre-, mid- and post-testing of the DBT group. In both
      groups, all instances behaviours related to anger and violence were monitored for
      three six-month periods, prior to, during and post-treatment. RESULTS: Overall,
      patients in the DBT group made greater gains than patients in the TAU group in
      reducing the seriousness of violence-related incidents, and in self report
      measures of hostility, cognitive anger, disposition to anger, outward expression
      of anger and anger experience. CONCLUSION: The results suggest a potential for
      DBT to impact positively and lastingly on violent behaviour and components of
      anger in male forensic patients when compared with standard treatment. The power
      of the current study to detect group differences was reduced by small ns, large
      confidence intervals, and a non-contemporaneous comparison group. Cost-effective
      strategies are proposed to take forward research on DBT with this population.

PMID- 14654872
TI  - [Perception of the impact of Bipolar Disorder and its diagnosis in health centers
      in Argentine and Chile].
AB  - OBJECTIVE: Early detection and treatment of Bipolar Disorder (BD) determine a
      significant relief in the considerable burden this disease implies. In order to
      adequately plan the strategies to guarantee access to treatment, it is useful to
      consider data which reflect the everyday vicissitudes the people affected by this
      pathology have to deal with. People on treatment for BD in centres in Argentina
      and Chile were surveyed, collecting data on their access to diagnosis and
      treatment. The centre surveyed in Chile, unlike those in Argentina, operates as a
      specialized unit. METHODOLOGY: An anonymous assisted survey was carried out; a
      random sample of people assisted in the participating centres with a diagnosis of
      BD type I or II, and stabilized for a period no shorter than 12 months, was
      assessed. RESULTS: 100 people were surveyed in Argentina and 69 in Chile (70%
      women, age 45.2 +/- 14.7, average schooling 12 years). Seventy one percent began
      symptoms at adult age (28,43 +/- 13 years), 14% during childhood. Age at first
      consultation was: 30 +/- 12.5; 85% reported having suffered psychotic symptoms,
      46.4% suicide attempts, 71% hospitalisations for BD. Sixty-nine percent reported
      diagnostic delays longer than a year (median 8 years), 75% reported having
      received other diagnosis prior to their BD diagnosis (62% unipolar depression,
      41% schizophrenia). Forty-one percent reported being unemployed. Delays and
      diagnostic errors were associated to a significant increase in the functional
      impact reported. CONCLUSION: Approximately 7 out of 10 people report difficulties
      in the access to a BD diagnosis. These difficulties magnify the already important
      impact of the disease.

PMID- 14654873
TI  - [Psychosocial aspects in osteoporosis].
AB  - Osteoporosis is a disease characterized by a decrease in bone mineral density
      which results in an increase in bone fracture. Its etiology is still unknown.
      Several risks factors have been described: increase in coffee intake, decrease in
      calcium intake, a sedentary lifestyle, a decrease in estrogen secretion and
      genetic factors. It has been recently shown that mood disorders, such as Major
      Depression associated with high levels of cortisone, constitute a risk factor for
      the development of osteoporosis. Psychoneuroimmunoendocrinology considers an
      integrated human being, a biopsychosocial unit permanently related to his
      environment, overcoming the cause - effect relationship. Taking into account this
      point of view we studied the psychoaffective and psychodynamic aspects in
      patients with osteoporosis. Several disorders have been found, an increase in
      anxiety indexes, depression, alexithymia, a larger number of early traumatic life
      events, a decrease in the support network and lower quality of life.
      Consequently, this pathology should be dealt with within an interdisciplinary
      framework. It is equally important to detect osteoporosis at an early stage in
      patients showing mood disorders.

PMID- 14654874
TI  - [Suffering and mental health during social crises].
AB  - In this paper the author analyzes the epidemiological data of the effects of the
      social crisis on the mental health against the background of the political and
      social events in Argentine in the last years. These effects are found both in the
      general population and in the health care professionals. The article reviews the
      clinical and psychopathological approaches to understand the disorders of the
      patients during a social crisis.

PMID- 14654875
TI  - [Social crisis and occupational fatigue among health professionals: warnings and
      resources].
AB  - Due to the crisis of the welfare state, the smashing of the state budget and the
      labour flexibility, the "helping professions" (health service, education, etc.)
      are the main assistance for the poor, the elderly people and the victims of
      violence. This result in the emergence of occupational pathologies, mainly in the
      health workers, such as burnout, secondary traumatic stress or empaty caused
      fatigue, mobbing or moral harassment -all of them affecting not only the quality
      of life of professionals but also the body health. The corporal disorders may
      begin with mild malfunctions, considered as "natural" facts of life, then
      becoming severe illness. The professional may attempt to meliorate the situation
      with the use of alcohol, tobacco, ansiolitics, etc. thus worsening the whole
      health. At the moment there are not legal regulations for this emergent
      pathologies. We have to pay attention to the signals in order to be able to
      overcome the dysfunctional defense mechanisms and to activate the preventive and
      protective resources, such as reflexion groups at workplaces.

PMID- 14654876
TI  - [Risk factors in the health care workers].
AB  - OBJECTIVE: The research has explored the possibility of the Burnout Syndrome in a
      group of nurses at a general hospital (San Luis, Argentina) working in different
      services. METHOD: Seventy four females and eight males, aged from 30 to 60 years
      were interviewed. The Maslach Burnout Inventory was used to assess three areas:
      emotional tiresome, depersonalization and personal realization. RESULTS:
      Significant differences were found between the three ages groups, indicating the
      incidence of age on the level of depersonalization. Regarding nominal variables,
      it was identified that working position was important to predict the Burnout
      Syndrome. CONCLUSIONS: It was concluded that a reevaluation of nursing human
      resources is necessary in order to prevent the burnout syndrome.

PMID- 14654877
TI  - [Suicide in convicts in Buenos Aires Province].
AB  - From January 2000 to July 2002, there had been 29 cases of suicide in prisons and
      forensic psychiatric hospitals of the Penitentiary Service of the Province of
      Buenos Aires. In the year 2000, the annual suicide rate in convicts was 14 times
      higher than that of the general population of the province of Buenos Aires.
      Ninety-three per cent of the suicides were committed by males. In this study,
      several characteristics and conditions associated with suicide are described.
      Among other findings, it is reported that forensic psychiatric population is at
      high risk for suicide.

PMID- 14654878
TI  - [Epidemiological features of admitted patients to a psychiatric unit in a Prepaid
      Medical Organization in Buenos Aires City].
AB  - OBJECTIVE: This paper addresses the issue of monitoring the features of the
      psychiatric inpatient population of a Prepaid Medical System in Buenos Aires
      City, paying special attention to its length of stay, diagnosis and readmission
      rate. METHOD: Between april 1 2000 and march 31 2002 all the psychiatric
      admissions have been registered and readmission rates and diagnosis prevalence
      were studied in a naturalistic setting. RESULTS: There were 244 admissions (0.8
      per thousand enrollees per year) and 17% was readmitted during this period (1 out
      of every 4 readmissions in the month following discharge). Their length of stay
      was an average of 11,8 days. 66% was admitted due to a suicidal attempt or
      suicidal thoughts. 42% had a discharge diagnosis of Mood disorder, 34%
      Personality disorder and 12% Schizophrenia or other psychosis. CONCLUSIONS:
      Inpatients belonging to this Prepaid Medical System seem to be different from
      other inpatient populations making the comparison among them hard to analyze.
      Future research should bring more data in order to perform further matching and
      benchmarking. This kind of information should be no secret and every System
      should be requested to show its results to allow users' and buyers auditory as
      well as State's control.

PMID- 14654879
TI  - [Creating conditions of more dignity. Interview with Salvador Celia by Ricardo
      Gorodisch].

PMID- 14654880
TI  - [Talent simulators. Individual expansion].

PMID- 14654881
TI  - [From psychiatric epidemiology to research in the field of mental health].

PMID- 14654883
TI  - To Morris F Collen: happy ninetieth!

PMID- 14654884
TI  - Leveraging information technology towards enhancing patient care and a culture of
      safety in the US.
AB  - OBJECTIVES: To heighten awareness about the critical issues currently affecting
      patient care and to propose solutions based on leveraging information
      technologies to enhance patient care and influence a culture of patient safety.
      METHODS: Presentation and discussion of the issues affecting health care today,
      such as medical and medication-related errors and analysis of their root causes;
      proliferation of medical knowledge and medical technologies; initiatives to
      improve patient safety; steps necessary to develop a culture of safety;
      introduction of relevant enabling technologies; and evidence of results. RESULTS
      AND CONCLUSION: Medical errors affect not only mortality and morbidity, but they
      also create secondary costs leading to dissatisfaction by both provider and
      patient. Health care has been slow to acknowledge the benefits of enabling
      technologies to affect the quality of care. Evaluation of recent applications,
      such as the computerized patient record, physician order entry, and computerized
      alerting systems show tremendous potential to enhance patient care and influence
      the development of a culture focused on safety. They will also bring about
      changes in other areas, such as workflow and the creation of new partnerships
      among providers, patients, and payers.

PMID- 14654885
TI  - Quality of health care: informatics foundations.
AB  - OBJECTIVE: To discuss in what ways computer systems can contribute to the quality
      of healthcare and on which principles of informatics successful systems are
      based. METHODS: Part of the information was obtained via a literature search and
      part is based on the knowledge of the authors. RESULTS: The results of the
      literature search are reported. The answers to the questions whether decision
      support is useful and which factors determine its success, the foundations of
      computerized guidelines systems and applications of physician order entry and
      medical risk management are presented. CONCLUSIONS: Despite many publications
      concerning diagnostic support systems their use in clinical practice is limited.
      Reminder systems do appear to have an impact on health outcomes. Standards for
      guideline models are being developed for effective sharing of guidelines across
      systems. Electronic patient records and physician order entry systems are useful
      aids in medical risk management.

PMID- 14654886
TI  - Virtual rehabilitation--benefits and challenges.
AB  - OBJECTIVES: To discuss the advantages and disadvantages of rehabilitation
      applications of virtual reality. METHODS: VR can be used as an enhancement to
      conventional therapy for patients with conditions ranging from musculoskeletal
      problems, to stroke-induced paralysis, to cognitive deficits. This approach is
      called "VR-augmented rehabilitation." Alternately, VR can replace conventional
      interventions altogether, in which case the rehabilitation is "VR-based." If the
      intervention is done at a distance, then it is called "telerehabilitation."
      Simulation exercises for post-stroke patients have been developed using a
      "teacher object" approach or a video game approach. Simulations for musculo
      skeletal patients use virtual replicas of rehabilitation devices (such as rubber
      ball, power putty, peg board). Phobia-inducing virtual environments are
      prescribed for patients with cognitive deficits. RESULTS: VR-augmented
      rehabilitation has been shown effective for stroke patients in the chronic phase
      of the disease. VR-based rehabilitation has been improving patients with fear of
      flying, Vietnam syndrome, fear of heights, and chronic stroke patients.
      Telerehabilitation interventions using VR have improved musculo-skeletal and post
      stroke patients, however less data is available at this time. CONCLUSIONS:
      Virtual reality presents significant advantages when applied to rehabilitation of
      patients with varied conditions. These advantages include patient motivation,
      adaptability and variability based on patient baseline, transparent data storage,
      online remote data access, economy of scale, reduced medical costs. Challenges in
      VR use for rehabilitation relate to lack of computer skills on the part of
      therapists, lack of support infrastructure, expensive equipment (initially),
      inadequate communication infrastructure (for telerehabilitation in rural areas),
      and patient safety concerns.

PMID- 14654887
TI  - Applications of virtual environments in medicine.
AB  - OBJECTIVES: This paper intends to investigate the role of virtual reality (VR) in
      medicine. In particular it outlines the current state of research and technology
      that is relevant to the development of effective virtual environments in
      medicine. METHODS: After describing the two different visions of VR we can find
      in medicine--the presentation of virtual objects to all of the human senses in a
      way identical to their natural counterpart, and a new human-computer interaction
      paradigm in which users are active participants within a computer-generated three
      dimensional virtual world--the paper presents some of the most interesting
      applications actually developed in the area. Finally, it discusses the clinical
      principles, technological devices and safety issues associated with the use of VR
      in medicine. RESULTS: With more than 1,000 VR papers already indexed in Medline,
      VR is a reality health care. Even if the number of controlled studies is still
      limited, its merging with emerging technologies like Ambient Intelligence and
      wireless communication will further improve its diffusion. CONCLUSIONS: The
      possible impact of VR on health care could be even higher than the one offered by
      the new communication technologies like Internet. In fact, VR is at the same time
      technology, a communication interface and an experience: a communication
      interface based on interactive 3D visualization, able to collect and integrate in
      single real-like experience different inputs and data sets. However, significant
      efforts are still required to move VR into commercial success and therefore
      routine clinical use.

PMID- 14654888
TI  - From passive to active electronic healthcare records.
AB  - OBJECTIVES: The provision of patient data to clinicians as and when it becomes
      available is a general objective of information systems in healthcare. It is
      known that the timely receipt of patient data can have a significant bearing on
      healthcare outcomes. One of the on-going tasks is to provide this data in the
      form of an Electronic Healthcare Record according to some agreed standard. The
      aim in this paper is to provide patient data in electronic form by pushing the
      information to the end users as soon it becomes available, in advance of any
      explicit request from the users. METHODS: This paper describes how an existing
      record system, the Synapses Federated Healthcare Records Server, has been
      extended to incorporate active functionality to facilitate pushing the
      information to end-user applications. The user must specify the information of
      interest to him, so that the system pushes only information useful to the final
      user. The approach proposed here relies solely on the use of callbacks through
      the middleware layer being used, a mechanism available in all existing middleware
      implementations. RESULTS: The Synapses Federated Healthcare Records Server which
      has resulted from this research is a more flexible and scaleable system, capable
      of fulfilling the needs of a wider range of healthcare organisation than when a
      strictly passive approach is used. CONCLUSIONS: It is shown that healthcare
      organisation can incorporate a healthcare record system with active functionality
      without any large investment or significant risk to their existing information
      systems.

PMID- 14654889
TI  - Modeling hospital information systems. Part 1: The revised three-layer graph
      based meta model 3LGM2.
AB  - OBJECTIVES: Not only architects but also information managers need models and
      modeling tools for their subject of work. Especially for supporting strategic
      information management in hospitals, the meta model 3LGM2 is presented as an
      ontological basis for modeling the comprehensive information system of a hospital
      (HIS). METHODS: In a case study, requirements for modeling HIS have been deduced.
      Accordingly 3LGM2 has been designed to describe HIS by concepts on three layers.
      The domain layer consists of enterprise functions and entity types, the logical
      tool layer focuses on application components and the physical tool layer
      describes physical data processing components. In contrast to other approaches a
      lot of inter-layer-relationships exist. 3LGM2 is defined using the Unified
      Modeling Language (UML). RESULTS: Models of HIS can be created which comprise not
      only technical and semantic aspects but also computer-based and paper-based
      information processing. A software tool supporting the creation of 3LGM2
      compliant models in a graphical way has been developed. The tool supports in
      detecting those shortcomings at the logical or the physical tool layers which
      make it impossible to satisfy the information needs at the domain layer. 3LGM2
      can also be used as an ontology for describing HIS in natural language.
      CONCLUSIONS: Strategic information management even in large hospitals should be
      and can be supported by dedicated methods and tools. Although there have been
      good experiences with 3LGM2 concerning digital document archiving at the Leipzig
      University Hospital, which are presented in part 2, the benefit of the proposed
      method and tool has to be further evaluated.

PMID- 14654890
TI  - Presenting XML-based medical discharge letters according to CDA.
AB  - The HL7 Clinical Document Architecture (CDA) is an important XML-based standard
      for the representation of clinical documents. OBJECTIVES: The use of Markup
      Languages could satisfy the demands of involved healthcare staff as well as the
      needs of patients, to receive an overview of the patient's treatment during the
      hospital stay. The standardization efforts of different groups dealing with this
      problem have demonstrated progress, but have not, as yet, achieved a routinely
      usable result. In particular, differentiating information according to a
      hierarchical order has not been published to date. METHODS: A retrospective
      analysis of 60 discharge letters from a cardiology ward (ward A) as well as 60
      discharge letters from a gastroenterology ward (ward B) were extracted from the
      central hospital information system, by taking every fifth discharge letter
      issued over a one year period. RESULTS: An XML-based prototype for medical
      discharge letters has been put in place representing the required information
      units and information elements. By means of an XSL-stylesheet, a detailed
      representation of the conventional discharge letter has been produced that is
      platform independent and permits the recurrent use of information units.
      CONCLUSIONS: Through the introduction of definitions like information elements
      and information units, progress in the development of CDA level two and three
      might be realized. We present a method by which discharge letters can be used by
      an Internal Medicine Department. This concept is implemented in a XML-based
      prototype allowing a special view on XML data to generate this document type.

PMID- 14654891
TI  - From phenotype to genotype: issues in navigating the available information
      resources.
AB  - OBJECTIVES: As part of an investigation of connecting health professionals and
      the lay public to both disease and genomic information, we assessed the
      availability and nature of the data from the Human Genome Project relating to
      human genetic diseases. METHODS: We focused on a set of single gene diseases
      selected from main topics in MEDLINEplus, the NLM's principal resource focused on
      consumers. We used publicly available websites to investigate specific questions
      about the genes and gene products associated with the diseases. We also
      investigated questions of knowledge and data representation for the information
      resources and navigational issues. RESULTS: Many online resources are available
      but they are complex and technical. The major challenges encountered when
      navigating from phenotype to genotype were (1) complexity of the data, (2)
      dynamic nature of the data, (3) diversity of foci and number of information
      resources, and (4) lack of use of standard data and knowledge representation
      methods. CONCLUSIONS: Three major informatics issues arise from the navigational
      challenges. First, the official gene names are insufficient for navigation of
      these web resources. Second, navigational inconsistencies arise from difficulties
      in determining the number and function of alternate forms of the gene or gene
      product and maintaining currency with this information. Third, synonymy and
      polysemy cause much confusion. These are severe obstacles to computational
      navigation from phenotype to genotype, especially for individuals who are novices
      in the underlying science. Tools and standards to facilitate this navigation are
      sorely needed.

PMID- 14654892
TI  - How to assess prognostic models for survival data: a case study in oncology.
AB  - OBJECTIVES: A lack of generally applicable tools for the assessment of
      predictions for survival data has to be recognized. Prediction error curves based
      on the Brier score that have been suggested as a sensible approach are
      illustrated by means of a case study. METHODS: The concept of predictions made in
      terms of conditional survival probabilities given the patient's covariates is
      introduced. Such predictions are derived from various statistical models for
      survival data including artificial neural networks. The idea of how the
      prediction error of a prognostic classification scheme can be followed over time
      is illustrated with the data of two studies on the prognosis of node positive
      breast cancer patients, one of them serving as an independent test data set.
      RESULTS AND CONCLUSIONS: The Brier score as a function of time is shown to be a
      valuable tool for assessing the predictive performance of prognostic
      classification schemes for survival data incorporating censored observations.
      Comparison with the prediction based on the pooled Kaplan Meier estimator yields
      a benchmark value for any classification scheme incorporating patient's covariate
      measurements. The problem of an overoptimistic assessment of prediction error
      caused by data-driven modelling as it is, for example, done with artificial
      neural nets can be circumvented by an assessment in an independent test data set.

PMID- 14654893
TI  - Comparison of fuzzy inference, logistic regression, and classification trees
      (CART). Prediction of cervical lymph node metastasis in carcinoma of the tongue.
AB  - OBJECTIVES: In this paper three statistical methods [logistic regression,
      classification and regression tree (CART), and fuzzy inference] for the
      prediction of lymph node metastasis in carcinoma of the tongue are compared.
      METHODS: A retrospective collection of data in 75 patients treated for tongue
      cancer was carried out at the Clinic and Policlinic for Oral and Maxillo-facial
      Surgery at the University Hospital of Freiburg in Germany between January 1990
      and December 1999; biopsy material was used for laboratory evaluations.
      Statistical methods for the prediction of lymph node metastasis were compared
      using ROC curves and accuracy rates. RESULTS: All three methods show similar
      results for the prediction of lymph node metastasis with slightly superior
      results for fuzzy inference and CART. A great overlap is apparent in the ROC
      curves. The best result observed for fuzzy inference and CART was a sensitivity
      of 79.2% [95% confidence interval: (57.8%; 92.9%)] and a specificity of 86.3%
      (73.7%; 94.3%); the best result for predictions based on the logistic regression
      was a sensitivity of 66.7% (44.7%; 84.4%) and a specificity of 80.4% (66.9%;
      90.2%). Accuracy rates of fuzzy method and CART were higher [accuracy rate for
      fuzzy method and CART: 84% (73.7%; 91.4%), for logistic regression method: 73.3%,
      95%-CI: (61.9%; 82.9%)]. CONCLUSIONS: From a clinical point of view, the
      predictive ability of the three methods is not sufficiently large to justify use
      of these methods in daily practice. Other factors probably on the molecular level
      are needed for the prediction of lymph node metastasis.

PMID- 14654894
TI  - Medical informatics specialists: what are their job profiles? Results of a study
      on the first 1024 medical informatics graduates of the Universities of Heidelberg
      and Heilbronn.
AB  - OBJECTIVES: Since 1972, the University of Heidelberg and the University of
      Applied Sciences Heilbronn have jointly been running a medical informatics
      program. To continuously provide high quality education, the curriculum is
      regularly evaluated among its graduates. The objectives of this study were to
      assess the job situation of the graduates and to evaluate the curriculum from
      their viewpoint. METHOD: Anonymous inquiry of all medical informatics graduates,
      having finished their studies before March 31, 2001 (n=1024) using a structured
      questionnaire. RESULTS: The questionnaire was answered by 446 (compliance: 45.5%)
      graduates. About one third (146 of 444 valid cases) are working in
      software/hardware companies. 179 (43.0% of 416 valid cases) graduates are working
      within medical informatics, 214 (51.4%) are working outside of medical
      informatics, but within other informatics. 23 (5.5%) graduates are working
      neither in medical nor in other informatics. 15 percent of the responding
      graduates have received a doctor's degree. Software engineering, database and
      information systems are regarded as most important parts of the education. The
      majority of the graduates are satisfied with their education as well as with
      their personal career. CONCLUSIONS: The variety of jobs, the job profiles, and
      the high level of our graduates' satisfaction with their education indicate the
      relevance of specialized medical informatics programs with a curricular profile
      like the one in Heidelberg/Heilbronn. Investigations like this can help to adjust
      the contents of the curriculum to professional needs.

PMID- 14654895
TI  - Alteration of the AT motif binding factor-1 expression in alpha-fetoprotein
      producing gastric cancer: is it an event for differentiation and proliferation of
      the tumors?
AB  - Alpha-fetoprotein producing gastric cancer (AFP-GC) rarely occurs, but it is
      classified as a special subtype of gastric cancer (GC). This tumor, as
      represented by the production of AFP, exhibits not only specific function but
      also different histology compared with ordinary-GC (O-GC). Clinically, it is
      likely to metastasize to the liver and, as a consequence, poor prognosis is
      recognized as one of the features. Recently, AT motif binding factor-1 (ATBF1)
      was identified as a modulator of AFP production by hepatocellular carcinoma, and
      the decreased expression of the protein was also reported in AFP-GC. However,
      little is known about the biological significance of the decreased expression. In
      this study, to clarify the biological characteristics of AFP-GC, antibody was
      raised against ATBF1 and immunohistochemistry was carried out. The antibody
      specifically recognized ATBF1, and the degree of expression could be
      characterized by immunohistochemistry. ATBF1 was expressed in O-GC and the area
      of tubular adenocarcinoma components of AFP-GC. On the other hand, the expression
      pattern varied in the hepatoid carcinoma components of AFP-GC, and AFP was
      expressed in the area without ATBF1 expression. Taken together, these results
      corroborated the previous reports that ATBF1 regulated AFP expression and
      inhibited transcription. Furthermore, in terms of differentiation induction,
      ATBF1 expression was decreased in the areas with little glandular formation. This
      may suggest that aberrant expression of ATBF1 induces the expression of various
      factors that are otherwise suppressed, and that this somehow determines the
      biological features of AFP-GC.

PMID- 14654896
TI  - Expression of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine
      dehydrogenase, E2F-1, Bak, Bcl-X, and Bcl-2, and clinical outcomes for gastric
      cancer patients treated with bolus 5-fluorouracil.
AB  - Few studies have investigated the biological factors associated with sensitivity
      to bolus infusions of 5-fluorouracil (5FU), including sequential methotrexate
      (MTX)/5FU therapy. We investigated the relationship between the expression of
      thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine
      dehydrogenase (DPD), E2F-1, Bcl-2, Bak, and Bcl-X, and the chemotherapeutic
      effects of sequential MTX/5FU. We studied 38 patients with unresectable or
      recurrent gastric cancer, treated weekly with sequential MTX/5FU (MTX 100 mg/m2,
      5FU 600 mg/m2, by bolus infusions, with a three-hour interval). Expression of the
      above proteins was examined in initial biopsy samples with immunohistochemical
      methods. Immunohistochemical reactivity was defined as positive when over 25% of
      cancer cells showed strong staining in the cytoplasm for TS, TP, DPD, Bak, Bcl-2,
      and Bcl-X, and in the nucleus for E2F-1. The overall response rate was 28% in the
      29 patients who had measurable lesions. Bak-negative patients showed a higher
      response rate than Bak-positive patients (39% versus 9%, respectively; p=0.1096),
      although expression of the other proteins was not associated with
      chemosensitivity. The median survival time (MST) of all patients was 256 days.
      Bak-negative patients survived significantly longer than Bak-positive patients
      (MST, 302 days versus 134 days, respectively; p=0.0044). Bcl-X-negative patients
      survived significantly longer than Bcl-X-positive patients (MST, 302 days versus
      215 days, respectively; p=0.0080). Furthermore, patients negative for both Bak
      and Bcl-X had significantly better prognoses than other patients (MST, 373 days;
      p<0.0001). Within the limits of the small patient population, multivariate
      analysis using the Cox proportional hazards model showed that Bak, Bcl-X, and
      histological type were independent variables predicting survival (p=0.0008,
      0.0081, and 0.0082, respectively). Although previously described predictive
      markers for protracted infusion of 5FU, including TS, TP, and DPD, might not be
      associated with clinical outcome in patients treated with sequential MTX/5FU, Bak
      may be a useful marker for chemoresponse and survival. Furthermore, both Bcl-X
      expression and the coupled expression of Bak and Bcl-X, as well as histological
      type, may be useful predictive markers for survival.

PMID- 14654897
TI  - Intratumoral genomic heterogeneity in primary head and neck cancer and
      corresponding metastases detected by dual-FISH.
AB  - Intratumoral genomic heterogeneity, which can be defined as both intersample and
      intrasample heterogeneity, is still a poorly understood phenomenon in head and
      neck squamous cell carcinoma (HNSCC) with presumed implications on tumor behavior
      and even prognosis. We analyzed 89 tumor specimen from 37 HNSCC patients by
      fluorescence in situ hybridization (dual-FISH) using specific DNA probes binding
      to centromeric sites of 6 chromosomes to investigate intratumoral heterogeneity.
      A derivation from disomy in at least 1/6 chromosomes was detected in 88/89 (99%)
      specimen. In 33% of these samples, a change in ploidy could be suspected.
      Intrasample heterogeneity was detected in 68/89 (76%). Intrasample heterogeneity
      was more pronounced in primary tumors than in metastatic tumors. Analysis of the
      intersample heterogeneity revealed notable differences between the 6 chromosomes
      with the highest discordance detected for chromosome 3 (46%) and the lowest for
      chromosome 11 (27%). Following our results, it seems important to us to underline
      that intratumoral heterogeneity exists as intra- and sample heterogeneity in
      HNSCC. Altogether, trisomic cells were significantly more frequent in primary
      tumors than in metastases (p=0.01) while, in turn, monosomic cells were
      significantly more frequent in metastases (p=0.029). In individual cases the
      extent of discordance between corresponding samples made a common clonal
      precursor unlikely. In these cases, the synchronous development of a primary
      tumor and a carcinoma of unknown primary ('CUP syndrome'), otherwise undetected,
      should be considered.

PMID- 14654898
TI  - Akt2 expression correlates with prognosis of human hepatocellular carcinoma.
AB  - Akt, a down-stream target of phosphatidylinositol-3 kinase, plays multiple roles
      in carcinogenesis. To elucidate its role in hepatocarcinogenesis, we
      immunohistochemically investigated the expression of Akt protein (Akt1 and Akt2)
      in tumor and non-tumor tissues from 56 patients with hepatocellular carcinoma
      (HCC). High expression of Akt2 in HCC tissues was detected in 21 cases (38%)
      while Akt1 expression was moderate or less in all cases. Low expression of Akt2
      was associated with histopathological differentiation, portal invasion and number
      of tumor nodules (p=0.026, 0.023, and 0.001, respectively). Univariate analysis
      showed that Akt2, histopathological differentiation, and portal vein invasion
      were significant prognostic factors (p=0.001, 0.028, and 0.006, respectively).
      Multivariate analysis revealed that in addition to histopathological
      differentiation, Akt2 was an independent prognostic marker (risk ratio for cancer
      relapse, 6.35, p=0.012). In contrast, Akt1 expression did not correlate with any
      clinicopathological features. Our findings suggest that Akt2, but not Akt1, is a
      novel independent predictor for the development and progression of HCC.

PMID- 14654899
TI  - Basic and clinical studies on quantitative analysis of lymph node micrometastasis
      in oral cancer.
AB  - Metastasis to cervical lymph nodes (LN) is significantly associated with the
      outcome of patients with oral cancer. To provide a useful method for the
      detection of micrometastases, we analyzed 115 LNs from 10 patients with oral
      cancer using real-time quantitative polymerase chain reaction (PCR) based on the
      expression of squamous cell carcinoma antigen (SCCA) and cytokeratin 13 (CK13).
      The sensitivity and quantification of this method were assessed by means of
      limited dilution of cultured oral cancer cells and a model of cervical LN
      metastasis established by inoculating green fluorescent protein (GFP)-expressing
      cells into the tongue of nude mice. In both investigations, a few cancer cells
      were detected by real-time quantitative PCR, but not by conventional reverse
      transcription-PCR (RT-PCR). SCCA mRNA was detected at high levels in metastatic
      LNs. In contrast, 26 of the 30 control cervical LNs did not express the gene at
      all, and the rest showed fairly low levels. Of 108 histologically metastasis
      negative LNs, 19 (17.6%) expressed SCCA mRNA levels higher than the cut-off value
      (1.0: mean expression of control LNs + 2SD). CK13 mRNA is not a suitable marker
      for the real-time PCR since it was detected frequently even in the control LNs.
      These findings suggest that genetic diagnosis by real-time quantitative PCR based
      on SCCA mRNA expression may be clinically useful for detecting occult tumor cells
      in cervical LNs.

PMID- 14654900
TI  - CD44 variant 6 expression predicts response to treatment in advanced colorectal
      cancer.
AB  - CD44 has diverse functions in cell-cell and cell-matrix interactions and may be a
      determinant of metastatic and invasive behaviour in carcinomas. CD44 variant 6
      (CD44v6) has been postulated to be involved in both carcinogenesis and tumor
      progression. Therefore, we have examined CD44v6 expression in tumors from 57
      patients with advanced colorectal cancer who received one of two chemotherapy
      regimes (either irinotecan alone or irinotecan and 5-flurouracil with folinic
      acid). CD44v6 expression was determined immunohistochemically in 57 paraffin
      embedded primary tumor sections and assessed using image analysis software.
      Strong expression levels of CD44v6 were seen in 24/57 (42%) of tumors, moderate
      levels in 17/57 (30%), weak levels in 9/57 (16%) and no expression was seen in
      7/57 (12%). The pattern of staining was predominantly cytoplasmic, 7/57 tumors
      also exhibited membrane specific expression. A significant association was found
      between tumor CD44v6 expression and treatment response (Fisher's exact test
      p=0.01). Only 1/12 patients with no or weak tumor expression of CD44v6 showed a
      response to treatment whereas 20/41 (49%) patients with moderate or strong CD44v6
      expression responded to treatment. Evaluation of CD44v6 expression of locally
      advanced and metastatic colorectal tumors may enable the clinician to identify
      and select patients that will show the best response to irinotecan based
      chemotherapy.

PMID- 14654901
TI  - Identification of lymphatic vessels in malignant, adenomatous and normal colonic
      mucosa using the novel immunostain D2-40.
AB  - Distribution of lymphatic vessels in normal and neoplastic colon has been
      previously analyzed with electron microscopic techniques, as reliable antibodies
      have not been available for selective lymph vessel staining. A novel monoclonal
      antibody, D2-40, is recently available to differentiate lymphatic vessels from
      blood vessels. In this study, we analyzed the distribution of lymphatic vessels
      in normal colon, adenomas with and without superficial stalk invasion and
      invasive carcinomas without identifiable polypoid precursor lesions. In contrast
      to previous studies, we found lymphatic vessels in superficially misplaced stalk
      stroma in adenomas, and closely associated with early invasive epithelial nests
      in invasive lesions. Lymphatic vessels were identified within the lamina propria
      of the in situ aspect of in invasive tumors. We conclude that lymphatic vessel
      structures are seen more superficially in adenomas and invasive carcinomas than
      previously described. Since intramucosal carcinomas in adenomas do not
      metastasize, these lymph vessels may be immature or not communicate with deeper
      lymphatics. Proliferation and distribution of lymphatic vessels may be related to
      prognosis and early metastasis.

PMID- 14654902
TI  - Expression of human telomerase reverse transcriptase mRNA in esophageal cancers
      and precancerous lesions.
AB  - Telomerase activity confers immortality to cells through stabilization of
      chromosomes and contributes to the development of most human cancers. Human
      telomerase reverse transcriptase (hTERT) is a catalytic subunit of telomerase.
      Expression of hTERT mRNA has been reported to be correlated with telomerase
      activity. The purpose of this study was to investigate localization of hTERT mRNA
      in human esophageal precancerous and cancerous lesions by in situ mRNA
      hybridization with avidin-biotin staining. Ki-67 immunoreactivity was also
      examined. We analyzed 51 squamous cell carcinomas, 9 dysplasias and 60 normal
      mucosae. The integrity of mRNA in each sample was verified with a poly-d(T)20
      probe. Seventy-eight samples (65%), including 35 carcinomas, 4 dysplasias and 39
      normal mucosae, contained intact mRNA. At the single-cell level, hTERT was
      expressed at high levels in both the cytoplasm and nucleus. In all cases, the
      majority of cancer and dysplastic cells showed high levels of hTERT expression.
      In all 39 normal mucosae, basal cells expressed hTERT mRNA, and this was also
      observed in infiltrating lymphocytes. The distribution of cells expressing hTERT
      was similar to that of Ki-67-positive cells. These results suggest that
      overexpression of hTERT mRNA may be correlated with proliferative activity
      reflected by Ki-67 immunoreactivity and is an early event in carcinogenesis of
      the esophagus.

PMID- 14654903
TI  - p53 expression and p21 expression are mutually exclusive in esophageal squamous
      cell carcinoma.
AB  - The accumulation of p53 protein, which is considered to be caused by a p53 gene
      mutation, is closely associated with poor prognosis in patients with certain
      types of carcinomas. The progression of esophageal squamous cell carcinoma (ESCC)
      is also suspected to depend on p53 gene status. We analyzed the relationship
      between p53 and p21 protein accumulation in ESCC, and simultaneously analyzed the
      frequency of apoptosis. Formalin-fixed paraffin-embedded sections were taken from
      46 patients who underwent esophagectomy for ESCC. These sections were examined by
      immunostaining with monoclonal antibodies PAb1801 and EA10 to determine p53 and
      p21 protein accumulation, respectively. We also analyzed the frequency of
      apoptosis by TdT-mediated dUTP-biotin nick end-labeling (TUNEL). For estimation
      of the proportion of stained cells, we used computer analysis with NIH image
      analysis software. p21 protein accumulation showed an almost inverse distribution
      to that of p53 protein. In areas where both p53 and p21 proteins were
      accumulated, few apoptotic cells were observed. Particularly in cases of mucosal
      tumors, p53 protein was prominently accumulated in the lower layer of the tumor,
      whereas p21 protein accumulation was confined to the upper layer. Our results
      suggest that progression of esophageal squamous cell carcinoma is controlled by a
      p53-dependent pathway.

PMID- 14654904
TI  - DPD activity and immunohistochemical DPD expression in human breast cancer.
AB  - We investigated dihydropyrimidine dehydrogenase (DPD) activity and its expression
      in breast cancer cases, and evaluated the prognostic significance of DPD
      expression in invasive breast cancer. A total of 49 paired of breast cancer
      tissues and the adjacent normal breast tissues were evaluated in this study. DPD
      expression of 191 patients with invasive breast cancer was also evaluated
      immunohistochemically. DPD activity in breast cancer ranged from 13.4-360.0
      pmol/mg/min (mean, 162.9 pmol/mg/min). DPD activity in breast cancer tissues was
      significantly (p<0.001) higher than in adjacent normal breast tissue. DPD
      activity was significantly higher in DPD expression-positive tumors than DPD
      expression-negative tumors. The level of DPD activity was correlated with DPD
      expression. Patients with DPD expression-positive tumors had a significantly
      (p<0.05) poorer prognosis in disease-free survival compared to those with DPD
      negative tumors. When evaluated in patients treated with 5-FU or 5-FU
      derivatives, DPD expression was a significantly (p<0.05) poorer prognostic factor
      in disease-free and overall survival. Using a Cox proportional hazards model,
      nodal status, ER status, and DPD expression were independent prognostic factors
      for both disease-free and overall survival. In conclusion, DPD expression may
      function as a marker of DPD activity and may be a prognostic indicator for
      patients with breast cancer.

PMID- 14654905
TI  - Gemcitabine suppresses malignant ascites of human pancreatic cancer: correlation
      with VEGF expression in ascites.
AB  - It has been reported that vascular endothelial growth factor (VEGF) is a potent
      angiogenic factor that also has the ability to increase vascular permeability.
      VEGF plays an important role in the development of malignant ascites in various
      cancers. Gemcitabine has been prescribed for patients with inoperable human
      pancreatic ductal carcinoma as a first-line chemotherapy. However, the response
      rates of patients with malignant ascites who were undergoing systemic
      chemotherapy were extremely limited. In the present study, we investigated the
      role of VEGF and the effects of gemcitabine on malignant ascites of human
      pancreatic ductal carcinoma. As an in vitro assay, the human pancreatic cancer
      cell line (SUIT-2) was incubated in DMEM supplemented with serially diluted
      concentrations of gemcitabine for 24 h. The expression levels of VEGF in culture
      media were assayed using an enzyme-linked immunosorbent assay (ELISA). As an in
      vivo assay, a cell suspension (1 x 10(7) cells in 100 microliters PBS) was
      injected into the intraperitoneal region. The mice were randomly divided into two
      groups (control and treated with gemcitabine). The mice were sacrificed four
      weeks after inoculation, the ascites volume was measured, and the extent of
      peritoneal dissemination was examined. The expression levels of VEGF and CD31 in
      peritoneal nodules were examined by immunohistochemistry. In addition, secreted
      VEGF protein levels were quantified using ELISA. The results show that VEGF
      levels in the culture medium decreased in response to gemcitabine in a dose
      dependent manner. The ascites formation and peritoneal dissemination within mice
      were suppressed by the treatment with gemcitabine. Immunohistochemical analysis
      suggested that expression of VEGF and CD31 in peritoneal nodules was suppressed
      by gemcitabine treatment, and the VEGF protein level in ascites was significantly
      decreased by gemcitabine (p<0.05). These results suggest that gemcitabine
      controls malignant ascites and peritoneal dissemination, either directly or
      indirectly, via VEGF. Moreover, intraperitoneal administration of gemcitabine may
      be a useful therapeutic approach for patients with malignant ascites in
      pancreatic carcinoma.

PMID- 14654906
TI  - Occult neoplastic cells in the lymph node sinuses and recurrence of primary
      breast, lung, esophageal, and gastric cancer.
AB  - The correlation between detection of occult neo-plastic cells (ONCs) in lymph
      node sinuses and the recurrence/metastasis of primary breast, lung, esophageal,
      and gastric cancer was examined. Among patients with Stage I-III cancer treated
      by radical resection with dissection of at least 10 lymph nodes, 40 patients who
      suffered recurrence/metastasis within 5 years post-operatively and 94 patients
      who did not have recurrence within 5 years were randomly selected. A total of
      1,340 lymph nodes were subjected to immunohistochemical staining for cytokeratin
      to identify ONCs. Then the sensitivity, specificity, positive predictive value,
      and negative predictive value of ONCs were determined for predicting the
      recurrence of each cancer. These parameters were respectively 40.0, 75.9, 62.4,
      and 55.8% for breast cancer, while the respective values were 50.0, 77.4, 68.9,
      and 60.8% for lung, 57.1, 64.3, 61.5, and 60.0% for esophageal, and 68.8, 65.0,
      66.3, and 67.5% for gastric cancer. All of the parameters exceeded 65% for
      gastric cancer. ONCs also showed a high specificity for breast and lung cancer,
      but both the sensitivity and specificity were low for esophageal cancer.

PMID- 14654907
TI  - Hot water soluble sesquiterpenes [anhydroperoxy-costunolide and 3-oxoeudesma
      1,4(15),11(13)triene-12,6alpha-olide] isolated from laurel (Laurus nobilis L.)
      induce cell death and morphological change indicative of apoptotic chromatin
      condensation in leukemia cells.
AB  - Hot water soluble (HWS)-sesquiterpenes [anhydroperoxycostunolide and 3-oxo
      eudesma-1,4(15),11(13)triene-12,6alpha-olide] were purified from Laurel (Laurus
      nobilis L.) and identified by Mass, and 1H- and 13C-NMR. These HWS-sesquiterpenes
      displayed strong growth inhibitory effect against human promyelotic leukemia HL
      60 cells. Apoptotic morphological changes of the nucleus, including chromatin
      condensation were induced in the HL-60 cells treated with the sesquiterpenes.
      Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were
      increased to 10.5, 46.5, and 91.3% after a 3 day-treatment with 2.5, 5 and 10
      micromoles anhydroperoxycostunolide, respectively. And the same analysis showed
      that the hypodiploid nuclei of HL-60 cells were increased to 9.8, 39.2 and 89.6%
      after a 3 day-treatment with 5, 10 and 20 micromoles 3-oxo-eudesma
      1,4(15),11(13)triene-12,6alpha-olide, respectively. These findings suggest that
      growth inhibition by anhydroperoxycostunolide and 3-oxo-eudesma
      1,4(15),11(13)triene-12,6alpha-olide of HL-60 cells results from the induction of
      chromatin condensation in the HL-60 cells. On the other hand, fragmentations by
      these compounds of DNA to oligonucleosomal-sized fragments were not observed in
      the HL-60 cells.

PMID- 14654908
TI  - Characterization of a highly aberrant plasma cell leukemia karyotype: a case
      report.
AB  - We report on a 72-year-old patient with a clinically diagnosed plasmocytoma which
      developed to a plasma cell leukemia (PCL) with so far unrecorded complex
      translocations. As GTG-banding was not able to resolve all karyotypic changes,
      multiplex-fluorescence in situ hybridization (M-FISH) in combination with
      microdissection based comparative genomic hybridization (micro-CGH) and
      multicolor banding (MCB) have been done. Using these molecular cytogenetic
      approaches the karyotype of the PCL case can be described as: 51,XY,-1,
      1,+3,+der(5)t(5;11;1)(5pter right curved arrow 5q13-q14::11q24 right curved arrow
      11q25::1q12 right curved arrow 1qter),+7 or +der(7)t(7;1)(7qter right curved
      arrow 7p15::1p31.1 right curved arrow 1pter),+8,+der(9)t(1;9)(1qter right curved
      arrow 1q12::9q12 right curved arrow 9pter),der(11)t(1;11;1)(1pter right curved
      arrow 1p31.1::11p15.5 right curved arrow 11q25::1q12 right curved arrow 1qter),
      13,der(14)t(X;14)(Xqter right curved arrow Xq21.3::14pter right curved arrow
      14qter),+15,+18,der(19)t(9;19)(9qter right curved arrow 9q12::19q11 right curved
      arrow 19pter),+i(19)(q10). The case shows one of the most complex karyotypic
      rearrangements ever described in PCL and indicates two additional chromosomal
      regions which may contain genes of interest for the development of this
      hematological disorder: loss of 1p10-p31.1 material and gain of Xq21.3-qter.

PMID- 14654909
TI  - Thalidomide prolongs disease stabilization after conventional therapy in patients
      with recurrent glioblastoma.
AB  - Thalidomide shows antiangiogenic activity and it has been successfully employed
      in various tumors. Considering the poor therapeutic options for glioblastoma and
      the role of angiogenesis in malignant glioma cells growth, we investigated the
      therapeutic activity of thalidomide in patients affected by recurrent
      glioblastoma. Inclusion criteria were: recurrent glioblastoma pretreated with
      surgery and radiotherapy, age >/=18 years, adequate performance status,
      hematological, renal, and hepatic functions. Exclusion criteria included severe
      underlying diseases, neuropathy or concurrent radiotherapy. Eighteen patients
      entered the study, 17 of whom were assessable for toxicity and response. Most of
      patients were pretreated with chemotherapy (77.8%). Thalidomide was well
      tolerated: the most common side effects were constipation (76.5% of patients),
      somnolence (47%), and peripheral neuropathy (11.8%). One minimal response (MR)
      and 8 stable disease (SD) were observed, with an overall clinical benefit of
      52.9%. Median time to progression and median overall survival (OS) for responders
      was 25 weeks (range 12-40) and 36 weeks (range 16-64), respectively. In
      conclusion, thalidomide induces modest side effects and it may be considered a
      valid therapeutic option for patients with recurrent glioblastoma.

PMID- 14654910
TI  - Safety and efficacy of concurrent interstitial radiation and hyperthermia in the
      treatment of progressive malignant brain tumors.
AB  - High activity 125I brachytherapy has efficacy in selected recurrent malignant
      brain tumors, but limited efficacy and risk of radiation necrosis have prompted
      investigation of additional adjunctive therapies. This study aims to assess the
      toxicity of interstitial conductive hyperthermia used concurrently with 125I
      brachytherapy for the treatment of recurrent brain malignancies. Twelve patients
      with recurrent malignant brain tumors were implanted using afterloading catheters
      intended to deliver 50 Gy at the isodose line encompassing the enhancing tumor
      with a 5-mm margin and heated to 41.5 degrees C for 48 h. The average implant
      volume was 18 cc with 5.3 catheters containing 9.4 sources with a total activity
      of 265 mCi. Serious toxicities included 8 motor deficits, 2 mood alterations, 4
      seizures and 2 catheter wound cerebrospinal fluid leaks. Median survival was
      10.35 months with the best responses being 6 with stable disease and 2 with
      partial responses. Reoperation rate for radiation necrosis was 33%. Concurrent
      conductive thermoradiotherapy is feasible but is associated with serious
      toxicity. There is no suggestion of improved survival with thermoradiotherapy
      over brachytherapy alone. Given the degree of toxicity observed, alternative
      approaches to improving local control of these tumors are being explored.

PMID- 14654911
TI  - Combination therapy with radiofrequency ablation and transcatheter
      chemoembolization for the treatment of hepatocellular carcinoma: Short-term
      recurrences and survival.
AB  - To evaluate short-term clinical results of radiofrequency (RF) ablation combined
      with transcatheter chemoembolization for the treatment of hepatocellular
      carcinoma (HCC) and to identify factors having influence on early intrahepatic
      recurrence. Sixty-four patients with 92 HCC lesions underwent RF ablation within
      2 weeks after chemoembolization. The maximum tumor size was small (</=3 cm) in 36
      patients, intermediate (3.1-5 cm) in 22 patients, and large (5.1-8.5 cm) in 6
      patients. Tumors were solitary in 42 patients and multiple (2 or 3) in 22
      patients. Factors affecting intrahepatic recurrence were evaluated by univariate
      and multivariate analyses. Intrahepatic recurrences were found in 13 patients
      (20%, 13/64) during the mean follow-up period of 18 months. Recurrences were
      found in the untreated liver in 11 patients and in both untreated liver and
      treated lesion in 2 patients. The cumulative intrahepatic recurrence rates were
      15% at 1 year and 43% at 2 years. In the univariate analysis, multiple tumor
      burden and large tumor size (>5 cm) were significantly linked with higher
      probability of early intrahepatic recurrence. In the multivariate analysis, tumor
      number was the only independent factor having significant impact on early
      intrahepatic recurrence. The estimated 1- and 2-year survival rates were 100% and
      93%, respectively. This combined therapy showed good early therapeutic effects on
      treated lesions and survival. Tumor number and maximum tumor size are important
      factors for early intrahepatic recurrence.

PMID- 14654912
TI  - Role of surgery in local treatment of Ewing's sarcoma of the extremities in
      patients undergoing adjuvant and neoadjuvant chemotherapy.
AB  - Although more and more patients with Ewing's sarcoma of bone (ESB) are being
      treated by surgery, the relative role of surgery and radiotherapy in the local
      treatment of this tumor has yet to be determined. Because the outcome of ESB may
      differ according to the anatomical site of the tumor, results reported in the
      literature, which generally refer to series with tumors located in all sites, may
      be selection biased. Therefore, we have retrospectively evaluated patients with
      ESB exclusively in the extremity and locally treated by surgery or radiotherapy.
      Two hundred and sixty-eight patients treated at Rizzoli 1979-1996 for non
      metastatic ES of the extremities were assessed. Chemotherapy was administered
      according to four sequentially activated protocols. One hundred and thirty-six
      patients were treated by surgery, 70 by surgery and radiotherapy, and 60 patients
      by radiotherapy. Two patients underwent only chemotherapy. The follow-up range
      was 5-23 years (mean 13 years). One hundred and fifty-two patients remained
      continuously free of disease, 108 relapsed, 2 died of chemotherapy toxicity and 6
      developed a second malignancy. The 5-year event-free survival (EFS) and overall
      survival (OS) were respectively 62 and 69%. Although patients of all groups were
      matched for possible risk factors, the rates of 5-year EFS and local control were
      significantly lower in patients treated with radiotherapy compared to patients
      treated by surgery or surgery and radiotherapy (48% vs 66%, p=0.002; 80% vs 94%,
      p=0.0001). Furthermore, in group 3 there were 6 secondary malignancies. Our
      results indicate that surgery should always be considered in the local treatment
      of ES of the extremities. Postoperative radiation therapy must be added in case
      of inadequate surgical margins.

PMID- 14654913
TI  - Nuclear accumulation of beta-catenin without an additional somatic mutation in
      coding region of the APC gene in hepatoblastoma from a familial adenomatous
      polyposis patient.
AB  - The APC (adenomatous polyposis coli) gene status in a familial adenomatous
      polyposis (FAP) patient who developed hepatoblastoma was analyzed by the yeast
      color assay. Although a single base insertion at codon 462 resulting in
      truncation of its product was documented in hepatoblastoma cells, no additional
      somatic mutation was detectable in the whole coding sequence of the APC gene. The
      nuclear accumulation of beta-catenin without mutation in the exons 2-4 of the
      beta-catenin gene, however, was observed in the tumor cells by
      immunohistochemistry. The similar nuclear accumulation of beta-catenin without an
      additional somatic mutation in its gene, in the absence of somatic mutation in
      cluster region of the APC gene, has been previously reported in the single FAP
      case. Moreover, review in the hepatoblastoma cases in the FAP families showed a
      relatively later onset of the disease when compared with the sporadic cases.
      These observations suggest that accumulation of beta-catenin without an
      additional somatic mutation in the APC gene might be a possible mechanism for
      tumorigenesis of hepatoblastoma in the FAP families.

PMID- 14654914
TI  - Differential alternative splicing expressions of telomerase reverse transcriptase
      in gastrointestinal cell lines.
AB  - Telomerase is a cellular RNA-dependent DNA polymerase that serves to maintain the
      tandem arrays of telomeric TTAGGG repeats at eukaryotic chromosome ends. One of
      the human telomerase components is hTERT, which has three alternative spliced
      sites that introduce eight isoforms of hTERT mRNA. The expression of these
      isoforms in gastrointestinal cell lines is unknown. We developed a PCR-based
      assay for detecting these splicing variants. In gastric and hepatocellular
      carcinoma cell lines, the gamma deletion variant and its combination variants,
      alpha- and gamma-, beta- and gamma-, and alpha-, beta- and gamma-deletion
      variants were frequently detected, while they were not detected in colorectal
      carcinoma cell lines. Our results provide important information of use for more
      detailed studies on the regulation of telomerase activity.

PMID- 14654915
TI  - Expression of the IAPs in multidrug resistant tumor cells.
AB  - We have investigated the expression of the IAPs (inhibitory of apoptosis
      proteins) in the human HL-60 leukemia and in its multidrug resistant, P
      glycoprotein (P-gp) over-expressing variant, HL-60R. HL-60R exhibits resistance
      to apoptosis induced from P-gp substrate drugs and also from other triggers
      (cisplatin, TNF-alpha, Fas ligation, TRAIL, IFN-gamma and serum starvation) not
      related to the multidrug transporter. Except for c-IAP-1 mRNA, HL-60R
      significantly over-expressed both the mRNAs and the proteins of all the IAPs
      studied, i.e. c-IAP-1, c-IAP-2, XIAP, NAIP and survivin. Determination of the DNA
      binding capacity of NF-kappaB (p50 or p65 subunits) indicated that, while HL-60
      cells show constitutive activation of p50 only, HL-60R cells contain the
      activated forms of both p50 and p65. Since p65 is necessary to form the NF-kappaB
      heterodimers able to increase transcription, its presence in HL-60R cells might
      well correlate to their increased levels of IAPs and, possibly of P-gp, which,
      reportedly, are NF-kappaB target genes. These results underline the possible role
      that the coordinated over-expression of the different IAPs may play in tumor cell
      resistance to drug induced apoptosis. Inhibition of NF-kappaB might be a useful
      strategy to block their up-regulation.

PMID- 14654916
TI  - No evidence for mutation of B-RAF in urothelial carcinomas of the bladder and
      upper urinary tract.
AB  - Mutational activation of the MAP kinase pathway is frequently found in various
      cancers. Recently, activating mutations in the B-RAF gene, an important activator
      of this pathway, have been described in several tumor types including melanoma,
      colorectal and papillary thyroid cancer. The most frequent mutation in exon 15
      (V599E), as well as several other mutations within exons 11 and 15 result in
      constitutive activation of the oncoprotein. In addition, a significant
      association between mismatch-repair (MMR) deficiency and the V599E mutation in
      colorectal tumors has been found. The aim of our study was to investigate B-RAF
      mutations in 121 urothelial carcinomas of the urinary bladder (ranging from pTaG1
      to pT4aG3) and 27 tumors from the upper urinary tract (UUT), including 16 tumors
      of the renal pelvis and 11 tumors of the ureter). Twelve of 27 UUT tumors were
      MMR-deficient and showed microsatellite instability. The V599E mutation was
      screened for by allele-specific PCR (PASA) and exons 11 and 15 of B-RAF including
      intron-exon-boundaries were sequenced. Overall, 116/121 bladder tumors and 23/27
      tumors of the UUT were successfully investigated by PASA. None of the tumors
      showed the V599E mutation. Sequence analysis of exons 11 and 15 was successful in
      46 urothelial tumors (bladder, n=31; UUT, n=15). No mutations within the coding
      region of exons 11 and 15 and the intron-exon junctions were found. The most
      frequent alterations in the B-RAF gene do not seem to be involved in urothelial
      carcinogenesis, and there is no correlation between MMR-deficiency and B-RAF
      mutations in urothelial tumors.

PMID- 14654917
TI  - Surrounding muscle edema detected by MRI is valuable for diagnosis of
      intramuscular myxoma.
AB  - We recently experienced 4 cases of intramuscular myxoma and analyzed MRI
      findings, comparing them with histological ones. Results showed that all tumors
      were depicted with a homogeneous low signal intensity on T1-weighted images and a
      markedly high signal intensity on T2-weighted images, findings which are similar
      to those of cystic lesions like intramuscular ganglions. However, tumors were
      diffusely and finely enhanced on T1-weighted images with intravenous gadolinium
      administration. Three cases showed the characteristic fat rim and fat cap. A
      diffuse edematous lesion demonstrating intermediate signal intensity on T1
      weighted images and high signal intensity on T2-weighted images was also found in
      the adjacent muscle surrounding the tumor in 3 of 4 cases. In this lesion, tumor
      invasion, diffuse and severe muscle degeneration, blood and lymphatic congestion
      with exudates, and reactive adipose tissue formation were observed. The present
      results suggested that for the clinical diagnosis of intramuscular myxoma with
      MRI examination, the combination of three MRI signs such as homogeneous low
      signal intensity on T1-weighted mages, markedly high signal intensity on T2
      weighted images, and an enhancement effect with contrast medium are important,
      but the fat rim or fat cap, and the surrounding muscle edema as detected by MRI
      are also characteristic and allow for a more firm diagnosis. We presume that the
      diffuse and severe muscle fiber degeneration induced by tumors may cause such
      specific surrounding muscle edema.

PMID- 14654918
TI  - Efficacy of boron neutron capture therapy on liver metastases of colon
      adenocarcinoma: optical and ultrastructural study in the rat.
AB  - The effect of neutron boron capture therapy (BNCT) was studied in rat tumor liver
      cells after induction of the liver metastases by splenic inoculation of cells
      from DHA/K12/TRb line. Ten days following the treatment, the BPA was injected
      into rats and therefore the animals were sacrificed, the liver was exposed to
      neutron irradiation and processed. In some experiments the liver was reimplanted
      (after irradiation) in syngenic animals and studied 3 days later, following
      sacrifice. Samples of tissue obtained from metastasised and non-metastasised
      areas of the liver parenchyma, before and after the neutron irradiation, were
      examined in light microscopy and electron microscopy. The analysis pointed out
      damages induced by the neutron treatment in single tumor cells mostly localised
      in the synusoidal blood stream. Debris and apoptotic cells were sometimes
      observed in the neoplastic nodules before treatment, while the tumor cell death
      (apoptosis) increased in the tumor cells following BNCT treatment. An intense
      scavenger activity of Kupffer cells after irradiation was accompanied by a strong
      acid phosphatase reaction detectable in wide cytoplasmic areas. In the liver
      parenchyma of reimplanted animals, the presence of large collagen bundles spread
      among the hepatocytes was observed at electron microscopy.

PMID- 14654919
TI  - Intratumoral injection of arsenic to enhance antitumor efficacy in human
      esophageal carcinoma cell xenografts.
AB  - To enhance the therapeutic efficacy of anticancer agents and to reduce systemic
      side effects, it was decided to study the effect of arsenic trioxide directly on
      solid tumors to observe the anticancer effect of arsenic on tumors and the
      distribution of arsenic in tumors and other organs. Esophageal carcinoma cells
      were heterotransplanted in severe combined immunodeficient (SCID) mice in both
      laterals of the abdominal wall. When both lateral tumors had grown to
      approximately 10x8x5 mm3, tumor-bearing mice were used for 2 experiments. The
      right tumors were treated with intratumoral injection of As2O3 in 1, 5 and 10
      micro g per day for 10 days sequent. The left tumors were treated with phosphate
      buffer solution as controls. To explore the distribution of As2O3 remaining in
      tumor and some organs, a single intratumoral injection of As2O3 was studied with
      quantitative measurement of arsenic by means of atomic absorption spectrometry.
      The results revealed that on the 17th day after the 1st injection As2O3-treated
      tumors were suppressed markedly compared to that of the contrarily lateral tumor
      accompanied by marked apoptosis and necrosis in tumor cells. The tumor growth
      inhibition (TGI) was 13.56, 62.37 and 76.92% in 1, 5 and 10 micro g group,
      respectively. There were no pathological changes in heart, lung, spleen, liver,
      kidney or brain after arsenic administration. Distribution of As2O3 revealed that
      As2O3 remained at higher concentration in arsenic-treated tumor tissue than in
      other organs. Our data suggest that intratumoral delivery of As2O3 efficiently
      suppresses growth of transplanted esophageal carcinoma without systemic side
      effects. The protocol of As2O3 intratumoral injection will be its potential
      clinical utility for therapy of solid tumors.

PMID- 14654920
TI  - Role of v-Raf and truncated form RAF1 in the induction of vascular endothelial
      growth factor and vascularization.
AB  - In this work we studied the effect of v-raf and different form RAF on up
      regulation of VEGF gene expression and angiogenesis. In the experiments the
      truncated forms of RAF1 gene were transfected into the cells of the established
      human urothelial line HCV-29, otherwise non-angiogenic. The plasmids coding for
      mitochondrial targeted dominant active or dominant negative RAF1 (DAM, DNM
      respectively) were deleted with RAS binding domain. DAM has the ability to
      phosphorylate BAD whereas DNM cannot phosphorylate BAD. DAM RAF1, similarly to v
      raf transfected cells, induced up-regulation of VEGF and caused angiogenic
      phenotype as studied in vivo. DNM RAF1 transfectants induced VEGF independent
      angiogenesis.

PMID- 14654921
TI  - Combined treatment with selective cyclooxygenase-2 inhibitor and fluorinated
      pyrimidines for liver metastasis of colon cancer.
AB  - Liver metastasis is a major contributor to mortality in patients with colorectal
      cancer. Hence, it is essential to establish preventive therapy to control liver
      metastasis. Recently, it has become widely accepted that cyclooxygenase (COX)-2
      inhibitors possess anti-cancer activity for various types of tumor, especially
      colorectal. The clinical application of COX-2 inhibitors may therefore be
      beneficial. In this study, we have developed a combined treatment with a
      selective COX-2 inhibitor and fluorinated pyrimidines for liver metastasis of
      colorectal cancer, and examined the effect of these agents on proliferation and
      invasion of a highly metastatic human colon cancer cell line, LM-H3. The COX-2
      inhibitor etodolac was found to inhibit cell invasion of LM-H3. 5-Fluorouracil (5
      FU) inhibited proliferation of this line in vitro. Etodolac did not increase the
      inhibitory effect of 5-FU on cell proliferation. We also examined the inhibitory
      effect of etodolac and UFT, belonging to the fluorinated pyrimidines, on liver
      metastasis by using a liver metastatic model in the nude mouse. Combined
      treatment with etodolac and UFT markedly reduced liver metastasis. Serious side
      effects were not observed. In conclusion, combined treatment with etodolac and
      UFT might be a promising preventive therapy for liver metastasis of colon cancer.

PMID- 14654922
TI  - A simple method for the simultaneous detection of E1A and E1B in adenovirus
      stocks.
AB  - Recombinant adenoviral vectors have been developed for use as therapeutic agents
      and for the introduction of exogenous genes into living cells. However, the
      occurrence of replication-competent adenoviruses (RCA) in adenovirus stocks
      produced in 293 cells remains a major problem in terms of the safe use of such
      vectors. To overcome the problems associated with the occurrence of RCA, we have
      established a simple method for the simultaneous detection of amplified E1A and
      E1B from RCA that might contaminate adenoviral stocks. The products amplified by
      polymerase chain reaction (PCR) were fractionated by regular electrophoresis on
      agarose gels and visualized by staining with ethidium bromide. This method is
      rapid and inexpensive for detection of RCA in the preparation of adenoviruses.

PMID- 14654923
TI  - Expression of multidrug resistance-1 and multidrug resistance-associated protein
      genes in pediatric rhabdomyosarcoma.
AB  - Overexpression of multidrug resistance-1 (MDR-1), and multidrug resistance
      associated protein (MRP) genes has been linked with resistance to chemotherapy in
      vitro and in vivo. Their role in chemotherapy resistance in pediatric
      rhabdomyosarcoma is unclear. The study was undertaken to analyze the expression
      of MDR-1 and MRP genes in the embryonal and the alveolar subtypes of
      rhabdomyosarcoma and to elucidate its clinical relevance. Twenty-three
      rhabdomyosarcoma samples were analyzed for the expression of MDR-1 and MRP genes
      using a semi-quantitative competitive RT-PCR assay. MRP gene expression was
      associated with a reduction in survival (p=0.02). The overall survival of
      patients with tumors positive or negative for MRP expression were 50% (95%
      confidence interval, 30-70%) and 93% (95% confidence interval, 76-100%)
      respectively. In contrast, the expression of MDR-1 gene was not predictive of
      survival. These findings suggest that MRP expression could be a prognostic factor
      in patients with rhabdomyosarcoma.

PMID- 14654924
TI  - Hypomagnesemia associated with chemotherapy in patients treated for acute
      lymphoblastic leukemia: possible mechanisms.
AB  - Body weight, height and lumbar spine bone mineral density (BMD) were measured in
      40 children (27 male, 13 female, aged 0.3-17.0 years) with acute lymphoblastic
      leukemia (ALL) at diagnosis and 6 months after initiation of chemotherapy, and in
      40 age- and sex-matched local healthy children. Serum and urinary biochemical
      indices of mineral metabolism were measured in the children with ALL at both time
      points. From diagnosis to 6 months, a reduction in the fractional excretion of
      magnesium was found. Serum osteocalcin was low at diagnosis and increased during
      chemotherapy, whereas 24-h urinary type I collagen cross-linked N-telopeptide was
      unchanged. The Z-scores for lumbar spine BMD increased and were correlated with
      the serum osteocalcin at 6 months. The change in serum magnesium was correlated
      negatively with the change in lumbar spine BMD, and with the lumbar spine BMD Z
      score at 6 months. After initiation of treatment for ALL, rapid recovery in bone
      formation, which results in the movement of extracellular magnesium into the
      skeleton through bone formation, may be an important contributor to
      hypomagnesemia.

PMID- 14654925
TI  - N-/C-terminal deleted mutant of human endostatin efficiently acts as an anti
      angiogenic and anti-tumorigenic agent.
AB  - Non-collagenous (NC-1) fragments at the C-terminus of basement membrane collagen
      IV, XV and XIII have been implicated as negative regulators of angiogenesis.
      Endostatin is an endogenous carboxyl-terminal fragment of collagen XVIII/NC-1,
      suppressing endothelial cell proliferation, migration in vitro and tumor growth
      in mouse models. Endostatin can bind zinc through N- and C-terminal residues.
      Here we demonstrate that N-/C-terminal deleted derivative of human endostatin,
      H5, effectively inhibited the proliferation of human umbilical vein endothelial
      cells (HUVECs). Also, tube formation in vitro was comparably inhibited either by
      H5 or endostatin. The anti-angiogenic and anti-tumorigenic activities of H5 and
      endostatin were confirmed by an in vivo assay using chick chorioallantoic
      membrane (CAM) and mouse models, respectively. Treatment of 30 ng of H5 inhibited
      the capillary formation in CAM by 50%. In addition, H5 exhibited more potent anti
      tumor activity than wild-type endostatin in in vivo mouse metastasis assay. These
      results indicate that the N-/C-terminal deletion mutant would be a strong
      candidate of anti-cancer agent against spontaneous tumor development and growth.

PMID- 14654926
TI  - Association of serum IL-6 levels with comprehensive geriatric assessment
      variables in a population of elderly cancer patients.
AB  - The primary aim of this study was to find whether any association exists between
      serum levels of proinflammatory cytokines, mainly IL-6, and the most important
      comprehensive geriatric assessment (CGA) variables such as functional status,
      cognitive functions and nutrition in a population of elderly cancer patients. The
      secondary aims were to find whether any difference existed between: i) age
      groups, ii) performance status scores, iii) patients who had lost weight versus
      those who had not. Eighty-four elderly patients with advanced cancer were
      included in the study (stage III 15.4%, and stage IV 72.6%). Serum levels of IL-6
      and CRP were significantly higher in elderly than in the other adult cancer
      patients. Among the CGA variables investigated, the most affected were functional
      status assessed by IADL, cognitive functions by MMSE and nutrition. The ECOG PS
      was shown to be significantly associated with all the dimensions of CGA
      investigated: poor PS (>/=2) corresponded to severe disabilities. As for the
      relationship of serum IL-6 with CGA variables, the strongest correlations were
      between IL-6 and functional status assessed by both Katz ADL (p=0.0003), IADL
      (p=0.0070) and nutrition (p=0.0013). Moreover, we observed an association,
      although not statistically significant, between functional disability (ADL and
      IADL) and high IL-6 levels in individuals with weight loss. IL-6 levels seem to
      be independently associated with all CGA variables investigated in the present
      study in a population of elderly cancer patients. Because the most important CGA
      variables, in particular functional status, have been observed to be strongly
      associated with survival, the present study, confirming our previously reported
      ones, suggests that IL-6 may be a reliable marker of disease outcome and supports
      the feasibility of using IL-6 as a sensitive outcome marker in studies based on
      novel approaches aiming at modifying age- and cancer-related biologic mechanisms.

PMID- 14654927
TI  - Chromosome 10 and 17 deletions and p53 gene mutations in Thai patients with
      astrocytomas.
AB  - The tumor suppressor gene locus is known to be partly responsible for the
      tumorigenesis of sporadic gliomas, but the genetic events that drive the
      neoplastic process of this tumor remain largely unknown. We correlated the
      results of loss of heterozygosity (LOH) analysis on chromosomes 10 and 17 and a
      point mutation analysis of a tumor suppressor gene, p53, in 21 patients with
      astrocytomas at different stages. LOH was determined in tumor and leukocyte DNAs
      of primary human central nervous system tumors. The incidence rate of brain
      tumors corresponded to every p53-coding exon for single-strand conformation
      polymorphisms (SSCP) and the mutations were confirmed by sequencing. p53
      mutations were found in 2 of 10 glioblastomas (20%) and in 1 of 8 low-grade
      astrocytomas (12.5%). Similarly, LOH on chromosome 10 was also found in 2 of 10
      glioblastomas (20%) and 1 of 8 low-grade astocytomas (12.5%). Neither of the p53
      mutations nor LOH on chromosome 10 was observed together in the tumor types
      analyzed. Interestingly, the p53 mutations were found in 29% of patients with LOH
      on chromosome 17. The fact that p53 mutation and LOH on chromosome 17 were found
      together only in glioblastomas, suggested that these genetic changes may
      accumulate during astrocytoma progression.

PMID- 14654928
TI  - Combined effect of aloe-emodin and chemotherapeutic agents on the proliferation
      of an adherent variant cell line of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic
      agents. The aim of the study was to determine if members of the anthraquinone
      family could be used as adjuncts to increase the growth inhibiting effect of
      anticancer agents in MCC. An adherent variant of MCC was derived from a
      previously established MCC cell line suspension. Cells were characterized by
      immunocytochemical methods using specific antibodies against epithelial (low
      molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron
      specific enolase, neurofilament protein, chromogranin A and synaptophysin)
      antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited
      proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin
      over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic
      agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5
      fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently
      inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin
      potentiated their inhibitory effect, especially when low concentrations of the
      anticancer compounds were used. The antiproliferative action of STI 571 may be
      associated with the presence of anti-c-kit antibodies. The combined use of
      anticancer agents, especially at low concentrations, and aloe-emodin may be
      considered a preferable means for treating MCC.

PMID- 14654929
TI  - Androgen receptor versus erbB-1 and erbB-2 expression in human prostate
      neoplasms.
AB  - A subject of current interest, especially in the development of androgen
      refractory prostate cancer, is the androgen receptor (AR) activation by growth
      factor receptors. Here, we report our work on the measurement of AR mRNA and
      protein expression in benign prostatic hyperplasia (BPH) and prostatic carcinoma
      (PCA) and evaluation of the relationship between AR, erbB-1 and erbB-2 gene
      expression determined in the same tissue. In order to define AR, erbB-1 and erbB
      2 in human prostate neoplasms 36 benign prostatic hyperplasia, 46 prostatic
      carcinoma and 12 normal prostate gland samples were analysed. According to
      distant metastasis PCA tissues were divided into two categories: i) T1-4N0-3M0
      (25 samples) and ii) T4N2-3M1 (21 samples). AR, erbB-1 and erbB-2 mRNA expression
      was estimated by RT-PCR. AR protein expression, both in nuclear and cytoplasmic
      fractions, was measured by Western blot technique. The association of AR mRNA and
      protein expression with erbB-1 and erbB-2 gene expression was evaluated. It was
      found that in clinically invasive (group II of PCA) prostate cancer cases AR mRNA
      expression was significantly correlated with erbB-2 mRNA expression (Spearman R
      coefficient 0.86, p<0.05). Interestingly, AR protein expression in this group of
      PCA was determined mainly in nuclear fraction. By Western blot AR protein was
      identified in 76.0% (16/21) and 23.8% (5/21) of PCA group II nuclear and
      cytoplasmic fractions, respectively. Furthermore, the mean AR protein level in
      nuclear fraction of clinically invasive (group II) PCA (0.82+/-0.04) was
      significantly higher (p<0.05) as compared to the normal group (0.56+/-0.11). In
      the case of T4N2-3M1 samples, significant correlation between AR protein level in
      nuclear fraction and erbB-2 mRNA expression (Spearman R coefficient 0.53, p<0.05)
      was stated.

PMID- 14654930
TI  - Synergistic action of piroxicam on the eicosapentaenoic acid-induced apoptosis is
      associated with enhanced down-regulation of anti-apoptotic Bcl-2 expression but
      not promoted activation of pro-apoptotic Bid protein.
AB  - Eicosapentaenoic acid (EPA) is a dietary polyunsaturated fatty acid (PUFA) that
      is found abundantly in fish oils and induces apoptosis in human promyelocytic
      leukemia HL-60 cells. Cyclooxygenase (COX) converts EPA intracellularly into
      various inflammatory mediators that may affect the bioavailability of this fatty
      acid for inducing apoptosis in the cancer cells. In this study, effect of
      piroxicam (PRX), a COX inhibitor, on the EPA-induced apoptosis in HL-60 cells was
      investigated. EPA arrested cell cycle of the leukemic cells at G0/G1 phase after
      8-h incubation and induced apoptosis after 24-h incubation. PRX induced neither
      cell-cycle arrest nor apoptosis significantly in HL-60 cells even after 48-h
      incubation. However, 24-h incubation with PRX followed by 24-h incubation with
      EPA significantly elevated both early-phase and late-phase apoptotic cells by 35%
      and 166% respectively, when compared to those induced by the fatty acid only.
      This synergistic action of PRX on the EPA-induced apoptosis was associated with
      enhanced down-regulation of anti-apoptotic Bcl-2 protein expression, but not
      promoted activation of pro-apoptotic Bid protein.

PMID- 14654931
TI  - Alterations of transforming growth factor beta receptor II, insulin growth factor
      receptor II genes in microsatellite unstable prostate carcinomas.
AB  - DNA from 45 primary prostate tumors and corresponding normal tissues were
      analyzed to detect whether the alterations of transforming growth factor beta
      receptor II (TGFbetaRII) and insulin growth factor receptor II (IGFRII) are
      associated with microsatellite instability (MSI). We identified that 25 tumors
      were microsatellite unstable (55%). The remaining 20 tumors are found to be
      microsatellite stable. Loss of heterozygosity (LOH) was also tested at various
      loci. Results indicate that in case of TGFbetaRII, the rate of frame-shift
      mutation depends on the number of polyadenine [poly(A)] tracts. Twelve percent of
      the tumors had frame-shift alteration at BAT-RII locus which has 10 poly(A)
      repeats. Twenty percent of the tumors had frame-shift at BAT-25 locus which has
      25 poly(A) repeats. In addition, IGFRII gene was examined for the presence of
      mutation in the repetitive sequences. Seven of the 25 tumors showed deletion of a
      G within eight poly(G) repeats. Besides these changes there were two tumors which
      showed a novel insertion of A within this poly(G) repeat making a change in 9
      samples (R4, 36%). On the other hand, 4 tumors showed changes within the 5CT
      repeats. In addition, 3 tumors showed another novel insertion of C within the CT
      repeats.

PMID- 14654932
TI  - Endovascular lung perfusion using high-dose cisplatin: uptake and DNA adduct
      formation in an animal model.
AB  - Mean survival after diagnosis of unresectable pulmonary metastases is less than
      one year. Isolated lung perfusion (ILP) is a technique that delivers chemotherapy
      into the pulmonary artery via a thoracotomy. Human trials are limited. We report
      an animal model for endovascular lung perfusion (ELP). Twelve swine were used.
      Treatment swine (N=6) received 150-mg of cisplatin (CDDP) into the pulmonary
      artery via a balloon occlusion catheter while nine grams of thiosulfate was given
      IV. Control swine (N=6) received 50-mg CDDP IV with sham pulmonary artery
      perfusion. Animals were sacrificed immediately (0 h), 4 or 24 h after infusion.
      Pulmonary and renal platinum/DNA adducts and serum CDDP levels were measured at
      all time points. Area under the adduct-time curve (AUA) was determined as a
      measure of systemic exposure. Pathologic study of the lungs was performed. At 0
      h, ELP elevated pulmonary adduct levels by 17.38 times while thiosulfate led to
      reduction in renal DNA adducts despite the elevated CDDP dose. At all time
      points, pulmonary adducts were at least 6.9 times higher for ELP compared to IV
      administration. The AUA was 7 times greater for the ELP group. Serum CDDP levels
      were significantly higher after ELP (p<0.05). There was no evidence of toxic
      pulmonary injury from ELP. Direct pulmonary artery infusion of CDDP results in
      greater DNA adduct formation than would be expected from simple dose escalation.
      Further study of ELP evaluating the acute and chronic effects of repeated
      treatment administration is warranted.

PMID- 14654933
TI  - Detection of telomerase RNA in the plasma of patients with breast cancer,
      malignant melanoma or thyroid cancer.
AB  - The crucial step in cellular immortalisation seems to be the activation of
      telomerase, the enzyme that synthesizes telomere repeat ending sequences. Since
      the telomerase activity has been detected in almost all types of cancer tissue it
      has been proposed as new reliable tumor marker. This study was conducted to
      evaluate the significance of appearance of circulating RNA for telomerase
      subunits hTR and hTERT in the plasma of cancer patients. Seven healthy
      volunteers, 25 primary breast cancer patients (stage I-III), 29 patients with
      advanced malignant melanoma (stage III-IV), and 4 patients with advanced thyroid
      cancer (stage III-IV) were included in the study. The total RNA was extracted
      from plasma samples, reverse transcribed to cDNAs, and specific cDNAs for hTR and
      hTERT were amplified by semi-nested PCR. In healthy volunteers, the control GAPDH
      was positive in all, hTR was positive in 3 cases, and hTERT was negative in all 7
      tested cases. Among 25 breast cancer patients, hTR was positive in 23, and hTERT
      in 12 patients. Two cases, that were hTR and hTERT negative, were at the same
      time negative also for GAPDH. Of the 29 patients with malignant melanoma, 24 were
      positive for hTR, and 17 for hTERT. Again, the 5 patients that were negative for
      hTR and hTERT, were negative also for the control GAPDH. In all plasma samples
      from thyroid cancer patients, hTR and hTERT were positive. In conclusion, the RT
      PCR followed by semi-nested PCR is a highly sensitive method for detection of
      circulating RNA in the plasma. Among the telomerase subunits, only hTERT could
      serve as an unspecific tumor marker in the plasma of cancer patients.

PMID- 14654934
TI  - Analysis of the RNA helicase A gene in human lung cancer.
AB  - In this study we investigated the RNA helicase A (RHA) gene localized on
      chromosome 1q25 in 15 lung cancer cell lines, 54 primary carcinomas, bronchial
      epithelial cells and normal lung. Both RT-PCR and real-time RT-PCR showed that
      RHA is over-expressed in tumour samples compared to normal lung tissues (p=0.01).
      There was a tendency for higher expression levels in small cell lung cancer
      compared to non-small cell carcinomas. Over-expression of Y-162 correlated with
      high grade tumours (p=0.023). However, there was no correlation with tumour stage
      and survival. Our observations are compatible with the role of RHA in lung cancer
      development.

PMID- 14654935
TI  - Potential roles of antisense therapy in the molecular targeting of genes involved
      in cancer (review).
AB  - Recent advances in antisense methods targeting genes involved in cell
      proliferation, angiogenesis, and apoptosis provide a potential anticancer effect
      alone as well as in combination with drugs, and antisense therapy may be useful
      in overcoming drug resistance and increasing survival in patients with advanced
      cancer including those with solid tumors. In particular, antisense to Bcl-2
      comprises a most promising therapy and is being tested in combination with
      anticancer drugs in randomized phase III trials for chronic lymphocytic leukemia,
      multiple myeloma, and malignant melanoma. The targeting of apoptosis-related
      proteins is promising for enhancing the effect of cancer chemotherapy. The
      molecular mechanism by which anticancer drugs induce apoptosis has been
      identified as mitochondrial dysfunction mediated by the release of cytochrome c.
      Modulation of multiple antiapoptotic signaling pathways involving Bcl-2 and Akt,
      which are related to growth factor-stimulated signal transduction in cell
      survival, is essential for enhancement of the cytotoxic effect of anticancer
      drugs. Herein, we review the current status of antisense therapy and its
      potential for enhancing anticancer drug-induced apoptosis.

PMID- 14654936
TI  - Bioassay using epidermal keratinocytes to determine phosphorylation status of the
      epidermal growth factor receptor in distant neoplasms.
AB  - We developed a bioassay to evaluate the phosphorylation status of a fibrosarcoma
      following systemic administration of the protein tyrosine kinase inhibitor PKI
      166. Samples of subcutaneous fibrosarcomas and distant skin were fixed in
      formalin, sectioned, and stained with several fluorescent antibodies against the
      epidermal growth factor receptor (EGF-R) and phosphorylated EGF-R. In mice given
      different doses of PKI 166, the dose-dependent inhibition of phosphorylation of
      EGF-R in epidermal keratinocytes paralleled that in fibrosarcomas growing
      subcutaneously, suggesting that skin biopsies can be used as surrogate tissues
      for distant neoplasms to determine the phosphorylation status of protein tyrosine
      kinase receptors.

PMID- 14654937
TI  - Expressional changes after histone deacetylase inhibition by valproic acid in
      LNCaP human prostate cancer cells.
AB  - Pathogenesis of prostate cancer is paralleled by aberrant transcriptional
      regulation which involves gene silencing by histone deacetylases. In cancer
      cells, inhibitors of histone deacetylases such as valproic acid can act as
      differentiation agents which relieve pro-apoptotic factors from transcriptional
      repression. We investigated the potential of the well-tolerated anticonvulsant
      valproic acid in prostate cancer cell line LNCaP and analyzed the activation of
      pro-apoptotic factors and resulting apoptosis. We used real time RT-PCR to
      quantify the mRNA expression of prostate-specific antigen, prostate-derived Ets
      transcription factor, tissue inhibitor of matrix metalloproteinase-3 and insulin
      like growth factor binding protein-3. An automated sandwich-ELISA was used to
      measure secretion of prostate-specific antigen in conditioned cell culture media
      of LNCaP prostate cancer cells. Apoptotic cells were detected cytochemically and
      by applying immunocytochemistry. Activity of histone deacetylases in nuclear
      extracts was measured with a colorimetric assay kit. Valproic acid treatment
      caused a marked inhibition of histone deacetylases activity. Expression of
      prostate-derived Ets transcription factor and consequently prostate-specific
      antigen were down-regulated to basal levels in LNCaP cells. Pro-apoptotic factor
      caspase-3, tissue inhibitor of matrix metalloproteinase-3 and insulin-like growth
      factor binding protein-3 were up-regulated resulting in apoptosis of tumor cells.
      Valproic acid mediates marked effects on the expression of genes relevant in
      proliferation and apoptosis. Our study provides strong evidence that prostate
      cancer may benefit particularly from anti-proliferative stimuli from this well
      established drug.

PMID- 14654938
TI  - Identification of CRASH, a gene deregulated in gynecological tumors.
AB  - We have identified CRASH, a human asparaginase-like protein which is composed of
      308 amino acids and exhibits 32% homology to human aspartylglucosaminadase at the
      amino acid level. Database analysis revealed that the gene corresponding to CRASH
      is composed of 7 exons and 6 introns. Steady-state level of CRASH mRNA was found
      to be increased in 5 cell lines derived from metastatic lesions compared with 2
      cell lines derived from primary mammary carcinoma and HMEC (human mammary
      epithelial cells). We found that the mRNA level of CRASH correlates with the
      metastatic propensity of several isogenic human colon cancer and pancreatic
      carcinoma cell lines. CRASH corresponds to a recently identified sperm
      autoantigen and furthermore we have demonstrated inducibility of CRASH mRNA by
      androgen and progesterone. Investigation of several types of human cancers and
      their corresponding normal tissues revealed high levels of CRASH mRNA in uterine,
      mammary and ovarian tumors compared with the corresponding normal tissues. CRASH
      mRNA expression was analysed in breast cancer samples with disclosed clinico
      pathological features and corresponding normal tissues. The levels of CRASH mRNA
      were significantly up-regulated in tumors compared with normal breast tissues and
      correlate with lack of estrogen receptor expression of the tumors.

PMID- 14654939
TI  - Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as
      a drug target for hepatocellular carcinomas.
AB  - To disclose mechanisms of hepatocellular carcinogenesis and to identify novel
      diagnostic markers and/or drug targets for treatment of hepatocellular carcinomas
      (HCCs), we analyzed expression profiles of clinical HCCs using a genome-wide cDNA
      microarray. From among the transcripts that were commonly up-regulated in these
      tumors we identified a novel human gene at chromosomal band 1p36.13, termed
      DDEFL1 (development and differentiation enhancing factor-like 1), encoding a
      product that shared structural features with centaurin-family proteins. The
      deduced 903-amino acid sequence showed 46% homology to DDEF/ASAP1 (development
      and differentiation enhancing factor), and contained an Arf GTPase-activating
      protein (ArfGAP) domain and two ankyrin repeats. Gene transfer of DDEFL1 promoted
      proliferation of cells that lacked endogenous expression of this gene.
      Furthermore, reduction of DDEFL1 expression by transfection of anti-sense S
      oligonucleotides inhibited the growth of SNU475 cancer cells, in which DDEFL1
      expression was highly up-regulated. Our results provide novel insight into
      hepatocarcinogenesis and may contribute to development of new strategies for
      diagnosis and treatment of HCC.

PMID- 14654941
TI  - Laser-induced autofluorescence microscopy of normal and tumor human colonic
      tissue.
AB  - Laser-induced autofluorescence (LIAF) spectroscopy has been found to be a
      promising tool for early cancer diagnosis in various organs, but the reasons
      responsible for the spectral differences between normal and diseased tissue are
      still not well understood. In this study, a microspectrophotometer (MSP) system
      was used to identify the microscopic origins of tissue autofluorescence in the
      colon under the excitation of a helium-cadmium laser at 442 nm. Colonic tissue
      samples (normal: n=8, adenocarcinoma: n=10) were obtained from 12 patients with
      known or suspected malignancies of the colon. The intrinsic fluorescence spectra
      and images of fresh tissue sections prepared from normal and tumor colonic tissue
      were measured by the MSP system. Three distinct tissue layers of the colon were
      found for fluorescence, the mucosa, the submucosa and the muscularis propria,
      with submucosa being the most fluorescent. Differences in the spectral shape and
      intensity of the intrinsic fluorescence originating from different colonic layers
      indicate that fundamentally different fluorophores may be present in the
      respective tissue layers. There was no significant difference in the intrinsic
      fluorescence features of the submucosa between normal and tumor colonic tissue,
      but the fluorescence intensity of the submucosa in tumor tissue was significantly
      reduced due to the infiltration of tumor cells into the submucosa. The intrinsic
      fluorescence spectrum peaking at about 520 nm for tumor stroma appeared more
      evident than that of normal lamina propria. Limited areas of the lamina propria
      layer in some adenocarcinoma colon exhibited an emission band at about 635 nm,
      which was attributed to endogenous porphyrins in tumor. Autofluorescence
      microscopy revealed that differences in the clinically measured autofluorescence
      spectra between normal and tumor tissue were mainly due to thickening of the
      tumor mucosa resulting in a reduced submucosa fluorescence contribution, as well
      as the increased hemoglobin absorption in tumor tissue. Therefore, investigation
      of the microscopic origins of tissue autofluorescence and images can provide new
      insights into morphological structures and biochemical components of tissues,
      which are vital to improve the implementation of the LIAF technique for non
      invasive in vivo tissue diagnostics.

PMID- 14654940
TI  - Experimental treatment of human neuroblastoma using live-attenuated poliovirus.
AB  - Neuroblastoma, originated from neural crest cells, is the most common
      extracranial solid tumor in childhood. In the present study, we evaluated in
      vitro the oncolytic effect of live-attenuated poliovirus on human neuroblastoma
      cell lines, and in vivo its therapeutic efficacy in human neuroblastoma-bearing
      athymic mice. Live-attenuated poliovirus killed 27 (93%) of 29 established
      neuroblastoma cell lines in vitro. It induced cleavage of eukaryotic translation
      initiation factor 4G, leading to cell death through a mechanism involving
      activation of caspase-9, caspase-3 and poly(ADP-ribose)polymerase. For the in
      vivo experiments, an animal model was established using athymic mice
      xenotransplanted with SJ-N-JF neuroblastoma cells on both flanks. Inoculation of
      live-attenuated poliovirus into one of the two tumors caused a dramatic and
      complete regression of both the inoculated and contralateral tumors. Live
      attenuated poliovirus has potent oncolytic activity against human neuroblastomas
      in vitro and in vivo and it may be useful for the treatment of advanced and
      refractory neuroblastomas, however, further studies are necessary to evaluate the
      safety of method.

PMID- 14654942
TI  - Involvement of the mitogen-activated protein kinase kinase 2 in the induction of
      cell dissociation in pancreatic cancer.
AB  - In our previous investigation, mitogen-activated protein kinase kinase 2 (MEK2)
      was detected as a factor which was correlated to the potential of invasion
      metastasis. In this study, the immunocytochemical, immunohistochemical and mRNA
      expressions of MEK2 were examined in pancreatic cancer cell lines and tissue
      samples, respectively. Constitutive expressions of MEK2 and phosphorylated MEK (p
      MEK) were observed in PC-1.0 and ASPC-1 cells, which exhibited a growth pattern
      of single cells, whereas the relevant expressions were quite faint in PC-1 cells
      and CAPAN-2 cells, which exhibited a growth pattern of island-like clonies.
      Simultaneous inductions of MEK2 expressions and cell dissociation were observed
      after the treatment with a conditioned medium (CM) of PC-1.0 cells. The
      expression of MEK2 and p-MEK were reduced and the cell aggregation was found in
      PC-1.0 and ASPC-1 cells after U0126 (a MEK inhibitor) treatment. In vivo, both
      the MEK2 and p-MEK overexpressed in human pancreatic cancer tissues and p-MEK was
      found to be more strongly expressed in the invasive front than that in the center
      of tumor (P<0.05). MEK2 is closely related to pancreatic cancer cell
      dissociation. MEK2 activation is probably involved in the first step of the
      cascade in the invasion-metastasis of pancreatic cancer.

PMID- 14654943
TI  - Presence of a modifier gene(s) affecting early renal carcinogenesis in the Tsc2
      mutant (Eker) rat model.
AB  - The Eker (Tsc2 mutant) rat model of renal carcinoma is an example of Mendelian
      dominantly inherited predisposition to a specific cancer. Effects of genetic
      background on renal carcinogenesis in the Eker rat model (Eker/Eker > Eker/BN
      strain) indicate the presence in the BN rat genome of a modifier gene(s) that
      suppresses tumorigenesis. The identification of such a modifier gene(s) might
      help clarify the diversity of tuberous sclerosis in humans. i) We found that
      preneoplastic lesions in 8-week-old F1 rats [(Eker x LE) and (Eker x BN)] were
      more numerous in the LE strain than in the BN strain although the difference was
      not large. ii) We next administered N-ethyl-N-nitrosourea (ENU; single injection,
      i.p.) at the age of 4 weeks to amplify the strain difference in tumorigenesis, as
      we had done in an earlier study to identify the predisposing gene. iii) This
      experiment was also done in BN congenic Eker rats to confirm the strain
      difference in tumorigenesis. Preneoplastic lesions were fewer in BN congenic rats
      than in Eker rats by a factor of 100. We used this ENU system to perform a
      backcross experiment [F1(Eker x BN) x Eker] and finally succeeded in mapping a
      new modifier locus on rat chromosome 5 (the LOD score of the D5Rat12 was 3.13).

PMID- 14654944
TI  - Combinational therapy for potential HIV-1 eradication and vaccination.
AB  - Eradication of HIV would avert the pandemic high rates of deaths and save the
      healthcare resources in treatment and prevention costs, however, it is clear that
      this goal is not achievable with existing anti-HIV drugs due to HIV evolvement in
      great magnitude and diversity. Despite recent reports of short interfering RNA
      directed silencing of HIV gene activities, there remain many challenges in
      overcoming the complications of HIV mutation in the management of clinical HIV
      infected cells. Here we describe a combinational therapy of antiviral
      deoxynucleotidylated RNA hybrid transfection and interleukin-2 adjuvant treatment
      that was able to consistently silence 99% mutant type HIV-1 infections of T
      lymphocytes mediated through a novel post-transcriptional gene silencing
      mechanism. This combined therapy not only induced strong suppression on mixed
      type HIV-1 replication but also boosted the immunity and proliferation of normal
      T lymphocytes. The outgrowth of non-infected T cells resulted in the elimination
      of 76% HIV-infected cells 1 week after the combinational therapy. These findings
      promise to provide an immediate therapy in both acute and chronic HIV infections
      as well as a potential vaccination strategy for AIDS eradication.

PMID- 14654945
TI  - Antitumor effects of peroxisome proliferator activate receptor gamma ligands on
      anaplastic thyroid carcinoma.
AB  - Anaplastic thyroid carcinoma is an aggressive neoplasm and resistant to all sorts
      of treatment due to its rapid growth and invasive potential. Peroxisome
      proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor
      modulating variety of biological properties, such as regulating of adipogenesis,
      inhibition of cancer cell proliferation or differentiation of tumor cells. The
      purpose of this study was to evaluate the possibility for the therapeutic effect
      of PPARgamma ligands against anaplastic thyroid tumor in vitro. Expressions of
      the PPARc gene and protein were examined in 5 human anaplastic carcinoma cell
      lines (MSA, IAA, ROA, K119 and KOA-2). We next evaluated the effects of PPARgamma
      ligands (Thiazolidinedione, Prostaglandin J2 and RS1303) on proliferation,
      differentiation, apoptosis and invasion. Five cell lines showed higher level of
      the PPARc gene and protein expression than papillary thyroid carcinoma. PPARgamma
      ligands inhibited cell proliferation by inducing apoptosis instead of
      differentiation in dose-dependent manner. PPARgamma ligands also down regulated
      the invasive potential of 5 cell lines. The inhibitory effect of proliferation or
      invasion was prominent in 3 cell lines, which exhibited higher expression level
      of the PPARc gene or protein. Our results indicated that PPARgamma ligands modify
      malignant potential of anaplastic carcinoma cell lines altering growth or
      invasive properties, suggesting that PPARgamma could be potentially the novel
      molecular target for human thyroid anaplastic carcinoma.

PMID- 14654946
TI  - Up-regulated expression of the MAT-8 gene in prostate cancer and its siRNA
      mediated inhibition of expression induces a decrease in proliferation of human
      prostate carcinoma cells.
AB  - In order to analyze differential gene expression of putative prostate tumor
      markers we compared the expression levels of >400 cancer-related genes using the
      cDNA array technique in a set of prostate tumors and matched normal prostate
      tissues. Up-regulated expression of mammary tumor 8 kDa protein (MAT-8),
      complement component C1S (C1S), ferritin heavy chain (FTH1), peptidyl-prolyl cis
      trans isomerase A (PPIA), RNA-binding protein regulatory subunit DJ-1 protein (DJ
      1) and vacuolar ATP synthase subunit F (ATP6V1F) was determined in prostate
      carcinoma and confirmed by using quantitative real-time RT-PCR analyses.
      Furthermore, quantitative real time RT-PCR on intact RNAs from 11 paired laser
      microdissected epithelial tissue samples confirmed up-regulated MAT-8 expression
      in 6 out of 11 prostate tumors. To determine the function of MAT-8 in vitro,
      human PC-3 and LNCaP prostate carcinoma cells were transfected with small
      interfering double-stranded RNA (siRNA) oligonucleotides against the MAT-8 gene
      leading to a specific down-regulation of MAT-8 expression. In addition,
      suppression of MAT-8 expression caused a significant decrease in cellular
      proliferation of both prostate cancer cell lines, whereas invasive capacity and
      cellular apoptosis remained unaffected. Taken together, our results indicate that
      the human MAT-8 gene contains the potential to serve as a prostate cancer
      expression marker and that MAT-8 plays an important role in cellular growth of
      prostate carcinomas.

PMID- 14654947
TI  - Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin
      antigen in pancreatic tumors.
AB  - Alterations in the expression of mucin family members play an important role as
      well as alterations in oncogenes and onco-suppressor genes in carcinogenesis and
      progression of pancreatic cancer. We analyzed the expression and localization of
      MUC1, MUC2, MUC5AC and small intestinal mucin antigen (SIMA) in pancreatic
      tumors. MUC1 expression was observed in almost all samples, whereas MUC2
      expression was not. MUC5AC expression was observed in 73.9% of the cancerous
      regions, 48.7% of the dysplastic regions and 72.0% of the hyperplastic regions
      but not in the normal pancreatic duct. SIMA expression was observed in 45.7% of
      cancerous regions, 17.9% of the dysplastic regions and 8.0% of the hyperplastic
      regions. Furthermore, stromal expression of MUC1, MUC5AC and SIMA was observed in
      37.0%, 60.9% and 26.1% of the cancerous regions, respectively. Stromal expression
      of these mucins was not observed in the hyperplastic regions and normal
      pancreatic duct and was observed in only two dysplastic regions. The survival of
      pancreatic cancer patients with stromal expression of MUC1 or SIMA was worse than
      that of other patients (P=0.04). In conclusion, the localization of mucin
      expression, especially stromal expression of MUC1 or SIMA, might be a prognostic
      factor for patients with pancreatic cancer.

PMID- 14654948
TI  - The role of p53 in the chemotherapeutic responses to cisplatin, doxorubicin and 5
      fluorouracil treatment.
AB  - A panel of tumour models used extensively for in vivo evaluation of new drugs was
      characterised for their p53 status. Basal p53 protein levels were measured by
      immunodetection on both formalin-fixed tumour tissue and from protein extracts of
      fresh tumours. High levels of nuclear-specific staining, indicative of p53
      mutation, was seen in 15/25 tumours, with the remainder showing intermittent or
      no staining. The functional status of p53 cDNA from these tumours was assayed
      within the functional analysis of separated alleles in yeast (F.A.S.A.Y.)
      reporter system. The cDNA from those tumours with high levels of p53 protein
      showed 14/15 failing to activate the reporter gene. The cDNA from tumours with
      low or non-detectable p53 levels showed 8/10 with wild-type p53. Tumours were
      grown subcutaneously in mice (n=10). Each mouse was given maximum tolerated doses
      for either doxorubicin, 5-fluorouracil or cisplatin. Tumour volumes were measured
      daily, alongside untreated controls. The specific growth delay values for each
      tumour were separated into two groups, those with functional p53 (wild-type) and
      those without (mutant and null status). The Mann-Whitney U test was performed on
      the groups of data, to evaluate differences in their response on the basis of p53
      status. Cisplatin was moderately active against tumours with wild-type and mutant
      p53 genes with no significant difference seen between both groups. However, a
      significant difference in specific growth delay was seen between the two groups
      when treated with doxorubicin or 5-fluorouracil (P=0.05), indicating a role for
      p53 protein in modulating the in vivo efficacy of these agents.

PMID- 14654949
TI  - Breakpoint differentiation in chromosomal aberrations of hematological
      malignancies: Identification of 33 previously unrecorded breakpoints.
AB  - Routine cytogenetic analysis provides important information of diagnostic and
      prognostic relevance for hematological malignancies. In spite of this, poorly
      spread metaphase chromosomes and highly rearranged karyotypes with numerous
      marker chromosomes, are often difficult to interpret. In order to improve the
      definition of chromosomal breakpoints multicolor banding (MCB) was applied on 45
      bone marrow samples from patients suffering from hematological malignancies like
      myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), chronic
      myelocytic leukemia (CML) or acute lymphoblastic leukemia (ALL). The breakpoints
      defined by GTG banding were confirmed by MCB in 8 cases, while in the remaining
      37 cases the breakpoints had to be redefined. In 20/45 cases the breakpoints
      could only be characterized after application of MCB. In summary, 73 different
      breakpoints were characterized, thereof 33 were previously undescribed. Eleven
      cases showed known acquired aberrations and 21 cases had previously described
      aberration types such as del(5q-), del(7q-), del(13q-) or t(1;5) as sole
      rearrangement or in connection with other complex ones. In a total of 11 cases 19
      breakpoints as described before were involved in hematological malignancies,
      while in 14 cases 33 breakpoints were identified which have not been described
      previously. Thus, MCB has proven to be a powerful and reliable method for
      screening of chromosomal aberrations, which considerably increased the accuracy
      of cytogenetic diagnosis.

PMID- 14654950
TI  - Somatic mitochondrial mutations in melanoma resection specimens.
AB  - As epidemiological data suggest ultraviolet (UV) radiation to be the major
      environmental factor for the development of melanoma, we screened this malignancy
      for UV-specific C right curved arrow T and CC right curved arrow TT DNA mutations
      as described in squamous and basal cell carcinomas of the skin. Mitochondrial
      (mt) DNA was addressed which is known to be highly more susceptible for mutations
      than nuclear DNA. In the mt genome we chose part of the non-coding displacement
      loop (D-loop) containing two hypermutable (C)n tracts especially prone for C
      right curved arrow T and CC right curved arrow TT changes. A total of 69 melanoma
      resection specimens was investigated by polymerase chain reaction (PCR) and
      single-strand conformation polymorphism (SSCP) electrophoresis, followed by DNA
      cloning and sequencing. We detected alterations of the mt D-loop fragment in 4/34
      (12%) melanoma primary tumours and in 7/35 (20%) cutaneous and subcutaneous
      metastases which was no statistically higher proportion upon Fisher's exact test
      (p=0.17). Among these 11 positive cases, 9 exhibited alterations in the (C)n
      microsatellite sequences indicating microsatellite instability (MSI) of mtDNA
      (C)n tracts. Besides 7 insertions and 2 deletions of nucleotides, 11 mutations
      occurred including only 4 UV-specific C right curved arrow T mutations in a
      nodular melanoma of the skin and in two subcutaneous metastases. CC right curved
      arrow TT mutations were not detected in any tissue sample. As (C)n tract
      alterations occurred in 2/9 primary melanomas with subsequent metastasis, whereas
      all 20 non-metastasizing cutaneous melanomas were not affected, these somatic
      changes may reflect genomic imbalance during tumour progression and may be useful
      for the assessment of patients' prognosis.

PMID- 14654951
TI  - Expression of alternatively and aberrantly spliced transcripts of the MDM2 mRNA
      is not tumor-specific.
AB  - The MDM2 proto-oncogene encodes a 90-kDa protein that binds to and inactivates
      the tumor suppressor p53. Several reports describe the presence of different
      alternatively, as well as, aberrantly spliced transcripts of the MDM2 mRNA in a
      variety of human cancers that have lost the ability to bind p53. Due to the
      transforming ability of at least some of the isoforms it has been suggested that
      they might contribute to tumorigenesis. Here we show that shorter MDM2
      transcripts are also widely expressed in normal tissues, including lung and renal
      tissue, and in lymphocytes. Alteration in MDM2 RNA transcripts were found in the
      majority of the samples. Although we cannot exclude that alterations in MDM2
      preferentially occur during cancer development, our data rather indicate that in
      this context the commonly observed transcript variants may also possess a normal
      physiological function.

PMID- 14654952
TI  - Coupling of RAFTK/Pyk2 kinase with c-Abl and their role in the migration of
      breast cancer cells.
AB  - Mitogen-induced changes in the actin cytoskeleton are accompanied by changes in
      the tyrosine phosphorylation of several proteins in focal adhesions. In this
      study, we have investigated the role of RAFTK (also termed Pyk2/CAK-beta), a
      cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin
      mediated signal transduction in breast cancer cells. Stimulation of T47D cells
      with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the
      formation of a multiprotein complex. Maximal phosphorylation of the proteins
      participating in this complex occurred within 2 h of HRG stimulation. Analyses of
      the members of the HRG-stimulated complex revealed that RAFTK associated with
      p190 RhoGAP (p190), RasGAP, c-Abl as well as with the focal adhesion molecules
      p130cas and paxillin. c-Abl was found to be associated with RAFTK through the
      region of RAFTK containing amino acids 419-1009. Site-directed mutagenesis of
      Y881 aa within the RAFTK sequence abolished the binding of RAFTK to c-Abl,
      indicating that the tyrosine residue 881 of RAFTK is the c-Abl binding site
      within the RAFTK molecule. Overexpression of wild-type RAFTK significantly
      enhanced breast cancer cell invasion, while overexpression of the mutants Tyr402
      or Tyr881 of RAFTK inhibited this migration. Therefore, RAFTK serves as a
      mediator and an integration point between focal adhesion molecules in HRG
      mediated signaling in T47D breast cancer cells.

PMID- 14654953
TI  - Treatment of minimal residual disease after surgery or chemotherapy in mice
      carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM
      CSF.
AB  - Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+,
      G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+),
      both of the H-2b haplotype and transplanted in syngeneic mice, were used to
      examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the
      treatment of minimal residual tumour disease. The mice carrying MHC class I+ TC-1
      tumour residua after surgery were injected into the site of the surgery either
      with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2.
      It has been found that both, the recombinant IL-2 and the IL-2 gene-modified
      tumour vaccine substantially reduced the percentage of tumour recurrences in the
      operated mice. Similarly, when the mice carrying TC-1 tumour residua after
      surgery were injected with recombinant GM-CSF, the recombinant GM-CSF inhibited
      growth of the tumour residua in the operated mice. Gene therapy with irradiated,
      GM-CSF secreting MK16 cells did not produce any tumour-inhibitory effect. In
      further experiments, mice bearing s.c. TC-1 tumours were injected i.p. with
      ifosfamide derivative CBM-4A and 8 days later, peritumourally, either with IL-2
      gene-modified and IL-2-producing MK16 cells, or with recombinant IL-2. It has
      been found that both, the recombinant IL-2 and the IL-2 gene therapy
      substantially reduced the percentage of tumour-bearing mice. When the mice
      bearing s.c. TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A
      and then, peritumourally, either with irradiated, GM-CSF gene-modified and GM-CSF
      producing MK16 cells, or with recombinant GM-CSF, it was found that both, the
      recombinant GM-CSF and GM-CSF gene therapy inhibited growth of tumour residua.
      Comparative experiments were performed with the MHC class I-, metastasizing
      tumour MK16. It has been found that both, recombinant IL-2 and GM-CSF, can
      inhibit growth of the tumour residua after surgery or chemotherapy. The lung
      metastases in mice with surgical minimal residual tumour disease or in mice with
      tumour residua after chemotherapy were inhibited by IL-2 but not by GM-CSF. The
      MK16 tumour vaccine producing IL-2 inhibited growth of tumour residua after
      chemotherapy, but not the tumour residua after surgery. The GM-CSF-producing
      vaccine was without significant effect in both, surgically- and
      chemotherapeutically-induced minimal residual MK16 tumour disease. In conclusion,
      the MHC class I+ and MHC class I-, HPV16-associated tumours were found to be
      sensitive to IL-2 and GM-CSF therapy after surgery or after cytoreductive
      chemotherapy. It is yet to be addressed if this is more general case with HPV16
      associated experimental tumours. If so, it would be of interest to further
      investigate whether such adjuvant therapy can also help to eradicate the residua
      after surgery and chemotherapy in patients carrying HPV16-associated neoplasms.

PMID- 14654954
TI  - Radiosensitizer effect of wortmannin in radioresistant bladder tumoral cell
      lines.
AB  - This work analyzes the effectiveness of wortmannin in boosting the lethality
      induced by different doses of X-rays, using the colorimetric assay of MTT.
      Bladder tumoral cell lines differing in radiosensitivity and p53 status were
      used. Since wortmannin is able to inhibit DNA-dependent protein kinase (DNA-PK)
      and rejoining of double-strand breaks (DSBs), we have analyzed the constitutive
      contents and expression after irradiation of the catalytic subunit of DNA-PK (DNA
      PKcs) in our cell lines with the aim of explaining the differential effect of
      wortmannin as radiosensitizer. Considering that DNA-PK is the main protein
      complex involved in DNA DSB repair, the ability to remove DSBs after irradiation
      (with or without wortmannin) was evaluated in the different cell lines by the use
      of pulse-field gel electrophoresis. Our results indicate a higher
      radiosensitization in the radio-resistant cell line that shows both high
      constitutive contents of DNA-PKcs and a high rate of DNA repair by the fast
      component. In contrast, no radiosensitizer effect of wortmannin was observed in
      the radiosensitive cell line, previously characterized as defective in DSB repair
      by a low repair fidelity, and - as our results show - with low constitutive
      contents and later post-irradiation expression of DNA-PKcs. No clear effect
      related to p53 status of the cell line was observed. These results suggest that
      high constitutive contents of DNA-PKcs are indicative of radio-resistant
      phenotypes, and analysis of the expression of this protein could be helpful in
      the optimal establishment of wortmannin as radiosensitizer in bladder tumoral
      cell lines.

PMID- 14654955
TI  - First clinical experience using a 'pathotropic' injectable retroviral vector
      (Rexin-G) as intervention for stage IV pancreatic cancer.
AB  - Metastatic or non-resectable (stage IV) pancreatic cancer has a rapidly fatal
      outcome (median survival: 3-6 months), thus making gene therapy a viable
      therapeutic option. The objectives of the clinical studies are to evaluate the
      safety/toxicity and potential anti-tumor response/efficacy of intravenous (i.v.)
      infusions of a 'pathotropic' retroviral vector bearing a cytocidal gene construct
      (Rexin-G) as a gene transfer intervention for stage IV pancreatic cancer. An
      intra-patient dose escalation regimen was used wherein increasing doses of Rexin
      G were given i.v. daily for 8-10 days. Completion of this regimen was followed by
      a one-week evaluation period for toxicity, after which, the maximum tolerated
      dose of Rexin-G was administered for another 8-10 days. In a second protocol,
      i.v. Rexin-G was administered frontline for 6 days followed by 8 doses of weekly
      gemcitabine. The NIH Common Toxicity Criteria Vs.2 was used to assess toxicity,
      and the NCI-RECIST criteria and tumor volume measurements were used to evaluate
      potential anti-tumor responses. We report the results of the first 3 patients
      that participated in the studies. Rexin-G arrested tumor growth in 3 of 3
      patients without experiencing dose-limiting toxicity. No bone marrow suppression,
      significant alterations in liver and kidney function, nausea and vomiting,
      mucositis or hair loss were observed. Two patients are alive with stable disease
      approximately 5 and 14 months from diagnosis, and 1 patient is alive with
      progressive disease 20 months from diagnosis. The encouraging results of this
      first clinical experience will guide the design and planning of phase I/II
      clinical trials to establish the safety and efficacy of Rexin-G as the first
      targeted injectable gene therapy vector for stage IV pancreatic cancer.

PMID- 14654956
TI  - Targeting cell cycle machinery as a molecular mechanism of sulforaphane in
      prostate cancer prevention.
AB  - Epidemiological studies recently concluded that consumption of cruciferous
      vegetables such as broccoli, cabbage, and cauliflower, etc. is inversely related
      to prostate cancer risk, although the mechanism of prevention and the responsible
      phytochemicals are unknown. Since clinically significant prostate cancer
      eventually can grow independent of androgen, the association of the growth and
      tumorigenesis of such prostate cancer cells with sulforaphane (SFN) which is a
      predominant isothiocyanate in cruciferous vegetables, investigated. These
      vegetables contain high concentrations of glucosinolate glucoraphanin, which
      yield sulforaphane when hydrolyzed by the plant enzyme myrosinase. This study
      showed that exposure of human androgen-independent DU-145 prostate cancer cells
      to SFN resulted in the inhibition of growth and tumorigenesis, as revealed by a
      reduction in cell density, DNA synthesis, and clonogenesis. Analyses of the
      mechanism revealed that SFN mediated cell cycle arrest by modulating the
      expression and functions of cell cycle regulators. SFN induced signals that
      inhibited the activity of cyclin-dependent kinase cdk4 with an up-stream
      induction of cdk inhibitor p21WAF-1/Cip-1, and reduced cyclin D1. The inhibition
      of cdk kinase activity could be affected with <1 micro M SFN within 24 h. As a
      result, phosphorylation of Rb proteins, which activates the transition from G1-
      to S-phase, was significantly decreased and the cell cycle progression retarded.
      SFN also down-regulated the expression of bcl-2, a suppressor of apoptosis, and
      activated caspases to execute apoptosis in the prostate cancer cells. The
      regulators of cell cycle have thus been revealed as targets of sulforaphane for
      growth arrest and apoptosis induction. The potential of SFN, as an active dietary
      factor to inhibit initiation and post-initiation of prostate cancer
      carcinogenesis is discussed.

PMID- 14654957
TI  - Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of
      phospholipid.
AB  - 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of phospholipid were shown
      to be highly antineoplastic against various tumor cells. In this study, we report
      that these conjugates are potent activators of protein kinase C (PKC, EC) in
      vitro. Although required Ca2+, PKC activation by the conjugates occurred even in
      the absence of phospholipid and diacylglycerol. Among the conjugates, 1-beta-D
      arabino-furanosylcytosine 5'-diphosphate-rac-1-O-octadecyl-2-O-palmitoylglycerol
      [(ara-CDP-DL-PBA); ara-C conjugate of ether phospholipid], was employed to
      investigate its mode of activation, since ether phospholipid has been reported to
      be a regulator of the PKC. When PKC was activated by ara-CDP-DL-PBA,
      diacylglycerol enhanced its activity with 3-fold reduction of an apparent Ka
      value for ara-CDP-DL-PBA and no change in the Vmax. During the PKC activation by
      phosphatidylserine, ara-CDP-DL-PBA exhibited a synergistic effect on the
      activation. Studies on the relationship between the structures of ara-CDP-DL-PBA
      and their effects on PKC activity showed that phosphate group of ether lipid was
      important for its activation of PKC, and that conjugation of ara-C and ether
      lipid further enhanced the enzyme activity. These results suggest that the ara-C
      conjugate of phospholipid activates PKC in a co-operative manner with
      diacylglycerol and/or phosphatidylserine, however, the exact mechanism of the
      antineoplastic effect of ara-CDP-DL-PBA through PKC activation still remains
      speculative.

PMID- 14654958
TI  - Correlation between complete response to anthracycline-based chemotherapy and
      topoisomerase II-alpha gene amplification and protein overexpression in locally
      advanced/metastatic breast cancer.
AB  - Anthracycline-based regimens are among the most active but also with greater risk
      of both acute and long-term side effects, namely cardiotoxicity. Predictive
      markers of response to anthracyclines are therefore essential. Topoisomerase
      IIalpha (topo-II) is the target of anthracyclines and preliminary data suggest
      its promising role as a predictive marker of sensitivity to these drugs. After
      screening a population of about 350 patients with locally advanced or metastatic
      breast cancer, two subgroups were selected for the present analysis: a study
      group (31 patients), composed of 14 complete responders (CR-a) and 17 true non
      responders (PD-a) to anthracycline-based CT, and a control group (28 patients),
      composed of 7 CR (CR-t) and 21 true non-responders (PD-t) to taxane-based CT.
      True non-responders were defined as progressive disease (PD) within the first
      three cycles of CT. Archival tumor samples of these patients were collected,
      biological markers evaluated and their status correlated with response to
      therapy. HER-2 and topo-II gene status were evaluated by FISH (Vysis multi-color
      probe-positivity cut-off: >/=2 ratio for HER-2 and >/=1.5 for topo-II), topo-II
      protein was evaluated by IHC (positivity cut-off >10%). All cases in which HER-2
      gene was non-amplified did not show topo-II gene aberrations. No association was
      found between HER-2 gene amplification and response to anthracyclines (5/14 (36%)
      CR and 5/17 (29%) PD to anthracycline-based CT were HER-2+). The topo-II gene was
      amplified in 3/14 (21%) CR but only in 1/17 (6%) PD to anthracyclines.
      Amplification of the topo-II gene was seen in 1/7 (14%) CR and in 3/21 (14%) PD
      to a taxane-based CT. Topo-II protein was overexpressed in 6/11 (55%) CR and in
      2/17 (12%) PD to anthracyclines, while in the control group, overexpression was
      seen in 5/7 (71%) CR and 8/20 (40%) PD. IN CONCLUSION: i) HER-2 gene
      amplification did not seem to be correlated with response to anthracyclines. ii)
      Both topo-II gene amplification and protein overexpression seem to correlate with
      response to anthracyclines, although other factors, such as p53 and cell
      proliferation, are most likely to be involved. iii) The role of combined
      evaluation of several relevant markers and of potential 'molecular signatures'
      are currently being evaluated in prospective randomized clinical trials.

PMID- 14654959
TI  - Immunohistochemical aid at risk stratification of melanocytic neoplasms.
AB  - There is increasing awareness of the population about the risk of cutaneous
      melanoma. In recent years, some improvement was gained in the early recognition
      of clinical warning signs using dermoscopy. As a result, the number of puzzling
      cases exhibiting limited classical clues for malignancy are submitted to the
      dermatopathologist. Thus, the risk of microscopic uncertainty or misdiagnosis may
      be increasing. The aim of the study was to assess retrospectively the
      contribution of immunohistochemistry in establishing the histological diagnosis
      of 520 melanocytic neoplasms. According to the disease evolution and the
      histological presentation, 6 profiles of phenotypical expressions were
      distinguished.

PMID- 14654961
TI  - The use of Alu-PCR to distinguish between typical pulmonary carcinoids versus
      classic midgut carcinoids.
AB  - Although histologically 'typical' pulmonary and 'classic' midgut carcinoids are
      similar, the small intestine tumors are more aggressive than their pulmonary
      counterpart. We believe that in contrast to pulmonary carcinoids arising from
      Kulchitsky cells, 'classical' midgut carcinoids develop from crypt stem cells
      that differentiate into endocrine ('classical') or exocrine-endocrine ('non
      classical' adenocarcinoid) tumors. The different progenitor cells may determine
      different malignant potentials between these types of carcinoids. To identify
      genetic differences between 'classical' midgut and typical pulmonary carcinoids
      using an Alu-PCR genomic profiling method, we reviewed 54 cases of carcinoid
      tumors that were surgically removed at Hartford Hospital from 1996 through 2001.
      Histologically these cases were selected into three groups: i) foregut or
      pulmonary carcinoids, ii) 'classic' midgut carcinoids of small intestine and iii)
      multiple typical pulmonary carcinoids. Genomic-profiling of DNA from these cases
      was performed using an Alu-PCR method. Metastases were observed in 18/20
      'classical' intestinal carcinoid tumors, 3/30 pulmonary carcinoids, and 0/4
      multiple pulmonary carcinoids. These results confirm that pulmonary carcinoids
      behave in a more benign fashion than intestinal carcinoid tumors. Using Alu-PCR
      to profile tumor cell genomic DNA, we showed that 68% of small intestine
      carcinoids and 58% of pulmonary carcinoids had allelic banding patterns
      suggestive of either amplification or deletion of gene sequences. Alu-PCR
      demonstrated loss or gain of genetic sequences that were unique for each examined
      group. These findings strongly suggest that pulmonary carcinoids differ from
      their intestinal counterparts.

PMID- 14654960
TI  - The transfection of thymidylate synthase antisense suppresses oncogenic
      properties of a human colon cancer cell line and augments the antitumor effect of
      fluorouracil.
AB  - 5-Fluorouracil (5-FU), a fluoropyrimidine analogue, is one of the most commonly
      used anticancer drugs for the treatment of gastrointestinal malignancies. Some
      studies reported that the cytotoxicity of fluoropyrimidines is mediated, in large
      part, by inhibition of the thymidylate synthase (TS), an essential DNA synthetic
      enzyme. The aim of this study was to determine if antisense TS technology could
      augment the chemosensitivity of human cancer cells to 5-FU. The full length
      coding region of TS cDNA was inversely cloned into the eukaryotic expression
      vector pCDL81 and transfected into DLD-1 cells. The expression and activity of TS
      were significantly suppressed in the antisense TS transfected cells.
      Interestingly, the transfection of antisense TS alone inhibited the cellular
      growth in vitro. The chemosensitivity to 5-FU was significantly increased in the
      transfected cells. The 50% inhibition values of 5-FU on DLD-1/anti-TS were
      approximately one forth that on parental cells. The augmentation of
      chemosensitivity to 5-FU was also confirmed in a nude mice model. The tumor
      growth of DLD-1/anti-TS cells was suppressed significantly more than that of DLD
      1 cells by the 5-FU. The expression and activity of TS in human colon cancer
      cells were effectively inhibited by TS antisense treatment and the effect of 5-FU
      to cancer cells can be augmented. The antisense TS technology could be promising
      for treatments of gastrointestinal cancers.

PMID- 14654962
TI  - Opioid growth factor inhibition of a human squamous cell carcinoma of the head
      and neck in nude mice: dependency on the route of administration.
AB  - Opioid growth factor (OGF), [Met5]-enkephalin, interacts with the OGF receptor
      (OGFr) to inhibit the growth of human squamous cell carcinoma of the head and
      neck (SCCHN) in vitro. Administration of OGF by daily intraperitoneal injection
      (i.p.) to animals with xenografts of CAL-27, a poorly differentiated SCCHN, is
      known to repress tumorigenic events. In this study, the ubiquity of OGF action on
      SCCHN was investigated by examination of OGF activity on SCC-1 tumors; this human
      cell line is well-differentiated and highly invasive. Mice receiving daily i.p.
      injections (10 mg/kg) of OGF had more than a 3-day delay in tumor appearance, and
      decreases in tumor volume ranging from 51 to 64% in comparison to controls
      throughout the experimental period. Receptor binding analysis for OGFr showed
      that binding capacity (Bmax) was 2.2-fold greater than control values, but
      binding affinity (Kd) was comparable. Plasma OGF levels did not vary between OGF
      and control groups. Mice receiving OGF by continuous infusion using minipumps, or
      by daily intratumoral injection, had characteristics of tumorigenicity similar to
      their corresponding control animals, although the OGF levels in mice receiving
      the OGF by minipump were elevated 18-fold greater than the control group. These
      data indicate that: i) the inhibitory action of OGF may be ubiquitous for SCCHN,
      ii) OGF treatment alters the characteristics of the OGF receptor but not of
      plasma OGF levels, and iii) the magnitude of effects of OGF on SCCHN is dependent
      on the route of administration.

PMID- 14654963
TI  - Ca(2+) sensing receptor activation by CaCl(2) increases [Ca2+]i resulting in
      enhanced spatial interactions with calbindin-D28k protein.
AB  - The extracellular calcium ion concentration, [Ca2+]o, sensing receptor CaR is a G
      protein coupled membrane receptor and it is involved in regulating cell
      proliferation, differentiation, secretion, and apoptosis. Calbindin-D28k is a
      high affinity calcium-binding protein that plays important roles in modulating
      the intracellular calcium ion concentration, [Ca2+]i, and thus influences signal
      transduction. The role of CaR in sensing and responding to [Ca2+]o and spatial
      interactions of CaR with calbindin-D28k in a distal tubule-like renal cell line
      are described. Fura-2 loaded Madin Darby bovine kidney (MDBK) cells were exposed
      to increasing concentrations of CaCl2 and the [Ca2+]i was determined by ratio
      fluorescence microscopy. The step-wise addition of CaCl2 caused continual
      increase in [Ca2+]i. The thapsigargin induced increase in [Ca2+]i observed in
      basal medium was eliminated by pretreatment of MDBK cells with 10 mM CaCl2
      thereby suggesting the involvement of endoplasmic reticulum Ca2+ stores in
      increasing the [Ca2+]i. CaR was localized in the plasma membrane by using
      confocal microscopy. The confocal microscopy data also showed CaR and calbindin
      D28k were co-localized when cells were exposed to 40 mM CaCl2. We postulate that
      sensing and responses to increasing [Ca2+]o that occur through CaR, increase the
      [Ca2+]i causing the translocation of Ca2+-bound calbindin-D28k towards CaR.

PMID- 14654964
TI  - Chromosomal imbalances in angioleiomyomas by comparative genomic hybridization.
AB  - Angioleiomyoma is a benign soft tissue tumor that usually develops in the
      subcutis of the lower extremities. It characteristically consists of thick vessel
      walls formed by proliferating smooth muscle cells, and vascular channels. Very
      little is known about the molecular cytogenetic changes in angioleiomyoma. In the
      present study, we employed comparative genomic hybridization (CGH) to identify
      relative DNA copy number changes in 33 angioleiomyomas using formalin-fixed and
      paraffin-embedded tumor tissues. CGH results were obtained in 23 (70%) cases.
      Eight (35%) of the 23 cases exhibited DNA copy number changes involving one or
      two chromosomes, whereas the remaining 15 cases exhibited no DNA copy number
      changes. The most common recurrent loss was found in chromosome 22 (the minimal
      common region was 22q11.2 in five cases). Recurrent gain was seen at Xq (three
      cases). High-level amplification was not observed. To our knowledge, this is the
      first report on molecular cytogenetic characterization of angioleiomyomas using
      CGH from formalin-fixed and paraffin-embedded specimen. The present study has
      identified chromosomal regions that may contain genes involved in the development
      of at least some angioleiomyomas.

PMID- 14654965
TI  - The pattern of gene copy number changes in bilateral breast cancer surveyed by
      cDNA microarray-based comparative genomic hybridization.
AB  - The nature of genetic alterations in bilateral breast cancer (BBC) associated
      with the distinctive development of a second primary tumor or a metastatic lesion
      is not clearly established. In this study, patterns of promoter methylation and
      gene copy number changes were assessed for their utility in the distinction of
      two types of BBC (synchronous and metachronous). Seven cases of synchronous and
      five cases of metachronous breast cancer tissues were used in X chromosome
      inactivation assay to assess the methylation pattern of human androgen receptor
      gene. X chromosome inactivation assay alone did not provide enough information to
      distinguish the genetic origins of synchronous and metachronous BBC. When four
      pairs of paraffin-embedded BBC tissues were used in cDNA array-based CGH with
      placenta DNA as a reference, higher DNA copy number changes were observed from
      metachronous pairs (9.0%) than from synchronous pairs (3.1%). From the two cases
      of metachronous pairs tested, 44 genes were found to be commonly modulated in
      gene copy numbers in a cancer detected later.

PMID- 14654966
TI  - Retinoic acid delays keratinocyte senescence by suppression of betaig-h3 and p16
      expression and induction of telomerase activity.
AB  - Retinoic acid (RA) plays an important role in the regulation of keratinocyte
      growth, differentiation, and senescence; however, the detailed mechanisms of RA
      regulation are still unclear. To investigate whether all-trans RA extends the in
      vitro lifespan of normal human epidermal keratinocytes (NHEKs) by affecting
      mitotic capacity and/or senescence, we studied the effects of all-trans RA on
      cell growth, senescence, the expression of betaig-h3 and Rb cell cycle
      regulators, and the telomerase activity of NHEKs after RA exposure. When primary
      NHEKs were cultured in medium containing 1 nM of all-trans RA, the proliferation
      and replicative senescence of the cells was significantly stimulated and
      inhibited, respectively, and the in vitro lifespan of the cells increased 1.4- to
      1.5-fold compared to the vehicle control. The levels of betaig-h3 and p16 in 1 nM
      of RA-treated cells remained significantly lower than that of the vehicle control
      at all population doublings. All-trans RA also triggered induction of telomerase
      activity in NHEKs with increasing a population doublings induced by RA treatment.
      These results support that the ability of all-trans RA to postpone, but not
      prevent, senescence may be related to both partial inhibition of p16 and betaig
      h3 expression and induction of telomerase activity.

PMID- 14654967
TI  - Thyroglobulin-pulsed human monocyte-derived dendritic cells induce CD4+ T cell
      activation.
AB  - Although thyroglobulin (Tg) would be expected to act as a tumor-associated
      antigen that might be exploitable by immunotherapy against thyroid cancers, it
      remains unclear how to effectively enhance the immune response to Tg in human
      since it is a self-component glycoprotein. We therefore tested whether and how
      human peripheral blood (PB) monocyte-derived dendritic cells (DCs) pulsed with
      human (h)Tg would induce activation of hTg-specific T cells. We found that
      immature DCs (iDCs) exhibited a higher endocytic capacity for fluorescein
      isothiocyanate-conjugated hTg than did mature DCs (mDCs). Although freshly
      isolated T cells responded poorly to mDCs, hTg-primed T cells responded much more
      strongly to hTg pulsed mDCs, which selectively induced IFN-gamma-secreting T
      cells. These results suggest that hTg-pulsed mDCs enhance the responses of Tg
      specific T cells, raising the possibility that vaccination with hTg-pulsed mDCs
      may be an effective approach as immunotherapy to potentiate thyroid cancer
      specific therapy.

PMID- 14654968
TI  - Expression of 12-lipoxygenase in human renal cell carcinoma and growth prevention
      by its inhibitor.
AB  - The metabolism of arachidonic acid (AA) by either the cyclooxygenase (COX) or
      lipoxygenase (LOX) pathway generates eicosanoids, has been implicated in the
      pathogenesis of a variety of human diseases, including cancer, and may play
      important roles in tumor promotion, progression, and metastasis. The involvement
      of 12-LOX expression and function in tumor growth and metastasis has been
      reported in both murine and human tumor cell lines. The expression of 12-LOX in
      human renal cell carcinoma (RCC), normal kidney (NK) tissues and 3 kinds of RCC
      cell lines (Caki-1, A498, RC-1), and its effects on cell proliferation in 3 RCC
      cell lines were examined. Expression of 12-LOX protein was detected by
      immunohistochemistry and 12-LOX mRNA in RCC cell lines was detected by nested RT
      PCR. Effects of 12-LOX inhibitor on RCC cell growth was examined by MTT assay,
      and to determine whether or not 12-LOX inhibitors induce apoptosis, we used
      Hoechst staining. While 12-LOX expression was detected slightly in NK tissues, a
      marked expression of 12-LOX was detected in RCC tissues. All human RCC cell lines
      expressed 12-LOX mRNA. The 12-LOX inhibitor baicalein caused marked inhibition of
      all three kinds of RCC cells in a concentration- and time-dependent manner. Cells
      treated with 12-LOX inhibitor showed chromatin condensation, cellular shrinkage,
      small membrane-bound bodies (apoptotic bodies), and cytoplasmic condensation.
      These results suggest 12-LOX may play a role in the progression of RCC in human
      tissue, and its inhibitors may become anticancer agents in human RCC.

PMID- 14654969
TI  - Hereditary multiple and isolated sporadic exostoses in the same kindred:
      identification of the causative gene (EXT2) and detection of a new mutation,
      nt112delAT, that distinguishes the two phenotypes.
AB  - Hereditary multiple exostoses (HME) is a well known autosomal dominant hereditary
      orthopedic disorder. Isolated exostoses, on the other hand, occur as sporadic
      events or as secondary post-traumatic sequel. The occurrence of solitary
      exostoses in individuals from pedigrees affected with HME may distort conclusions
      about carrier status and/or diagnosis. Both conditions are potentially malignant
      and both are associated with genetic alterations in either EXT1 or EXT2 genes. In
      this study, we present a seven-generation family from western Sweden consisting
      of 170 blood relatives, 38 of whom had multiple cartilaginous exostoses, while 8
      had isolated exostoses. Linkage analysis aimed to discern one of the known EXT
      genes demonstrated linkage of the HME phenotype to the EXT2 gene. Subsequent
      mutation analysis revealed a novel mutation, nt112delAT, in this gene. All
      carriers of the detected mutation had multiple exostoses, indicating full
      penetrance. None of the pedigree members with isolated exostoses were carriers of
      the detected mutation. Two of the mutation carriers developed chondrosarcoma
      yielding a 5.2% risk of malignant development for this mutation. The detection of
      this mutation has enabled us to provide appropriate genetic counseling concerning
      this complex situation.

PMID- 14654970
TI  - Mutational analysis of the BAK gene in 192 advanced gastric and colorectal
      cancers.
AB  - The evasion of apoptosis has been linked to the development of cancer. A recent
      study of a small number of gastric and colorectal cancers found that the BAK
      gene, which encodes a pro-apoptotic protein, contained somatic mutations in
      approximately 17% of the samples analyzed. To investigate the precise frequency
      of BAK mutations, we examined the entire coding sequence of the BAK gene in
      gastric and colorectal cancers, using polymerase chain reaction-single-strand
      conformational polymorphism (PCR-SSCP) analysis and direct sequencing. We could
      not detect any somatic mutations of the BAK gene in 192 colorectal and gastric
      cancers. We found only four single-nucleotide substitutions in the coding
      sequences, which were also found in corresponding normal samples. We conclude
      that somatic alterations of the BAK gene are rare in colorectal and gastric
      cancers.

PMID- 14654971
TI  - Epimorphin expression in human colonic myofibroblasts.
AB  - Epimorphin is a membrane-associated protein that has been postulated to regulate
      epithelial morphogenesis in several tissues. However, epimorphin expression in
      the human intestine has not been fully investigated. In this study, we
      investigated epimorphin expression in the inflamed mucosa of inflammatory bowel
      disease (IBD). Tissue samples were obtained surgically from patients with active
      ulcerative colitis (UC) (n=5) and active Crohn's disease (CD) (n=5). Epimorphin
      and alpha-smooth muscle actin (SMA) were stained immunohistochemically.
      Epimorphin expression in human intestinal subepithelial myofibroblasts (SEMFs)
      was analyzed by Western and Northern blotting. In the normal colon, epimorphin
      expression was detected partly in the alpha-SMA-positive cells under the
      epithelial cells. Epimorphin was also expressed in alpha-SMA-positive cells in
      the capillary wall. In the inflamed mucosa of UC and CD patients, epimorphin
      expression was not altered. In isolated human SEMFs, epimorphin was detected as a
      single band of molecular weight 34-kDa under reducing and non-reducing
      conditions. In intestinal SEMFs, epimorphin mRNA expression was not affected by
      inflammatory cytokines and growth factors. Epimorphin was constitutively
      expressed in the normal colonic mucosa, and this was not altered in the inflamed
      mucosa of IBD patients. The localization of epimorphin may indicate a potential
      role in maintaining normal tissue structure in normal and IBD mucosa.

PMID- 14654972
TI  - Increased amplification proximal to the MLL gene in acute myeloid leukemia.
AB  - Amplification of the chromosomal region 11q23 encompassing the MLL gene has been
      observed in patients with acute myeloid leukemia (AML). Patients with this
      abnormality often have a poor response to chemotherapy and short survival. We
      have studied the regions flanking the MLL gene using 8 bacterial artificial
      chromosome (BAC) probes and dual color fluorescence in situ hybridization (FISH)
      analysis. Two contigs of BAC probes flanking the MLL gene, were constructed by
      standard primer walking and BAC end sequencing. For comparison, metaphase
      chromosome preparations were also hybridized with a commercial MLL specific
      probe. Metaphase chromosomes were prepared from the bone marrow sample of an 80
      year old female patient with AML-M1 and the cytogenetic aberration der(11)hsr(11)
      (q23). FISH analysis on metaphase chromosomes showed amplification on the
      homogeneously staining region (hsr) and marker chromosomes for both the MLL gene
      and the BAC probes. Using dual color FISH, probes proximal to MLL showed greater
      amplification than those distal to MLL, as represented by additional red signals
      on both metaphase and interphase chromosomes. Ratios of the copy numbers of the
      BAC probes relative to the chromosome 11 centromere copy number confirmed a
      higher copy number for probes proximal to MLL. These results suggest that other
      gene(s) proximal to MLL could be the target gene(s) of amplification in this case
      and not the MLL gene as previously assumed.

PMID- 14654973
TI  - Reactive oxygen species-producing site in radiation-induced apoptosis of human
      peripheral T cells: involvement of lysosomal membrane destabilization.
AB  - In our previous studies, we have partly elucidated the mechanism of radiation
      induced apoptosis of human peripheral T cells. The exact site of the ROS
      (reactive oxygen species) formation induced by irradiation has been so far
      unknown. Therefore, in this study, we investigated the site of ROS formation by
      utilizing MitoCapture, H2DCFDA (succinimidyl ester of dichlorodihydrofluorescein
      diacetate), DAPI, and Lysosensor. Our results showed that ROS formation
      apparently originated in the mitochondria and/or lysosomes instead of in the
      nuclei of irradiated T cells. Moreover, lysosomal swelling and deformity,
      possibly revealing lysosomal membrane instability, were observed at 1 h after 5
      Gy irradiation of T cells. At 4 h after irradiation of 5 Gy, increase of
      fluorescence around the lysosomes, possibly revealing lysosomal rupture, was
      seen. Based on the above results, we concluded the possible existence of a new
      apoptotic cascade involving early lysosomal membrane destabilization in radiation
      induced apoptosis of human peripheral T cells. Therefore, possible involvement of
      lysosomal protease leakage caused by hydroxyl radical formation in lysosomes
      (possibly resulting in mitochondrial membrane dysfunction) is considered to play
      an important role in radiation-induced T cell apoptosis.

PMID- 14654974
TI  - Early response to interferon alpha treatment and long-term clinical outcome in
      Japanese patients with chronic HBV genotype C infection.
AB  - Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor
      clinical outcome and less favorable response to interferon (IFN) alpha therapy
      compared to genotype B. We evaluated the response to IFN alpha therapy and long
      term clinical outcome in Japanese patients with chronic active HBV genotype C
      infection. Thirty Japanese patients with chronic active hepatitis who received
      natural IFN alpha therapy were followed for 2-12 years (mean 5.9 years). Twenty
      four patients were treated short-term (daily for 4 weeks at a mean total dosage
      of 174 million units) and 6 patients were treated long-term (total of 26 weeks at
      a mean total dosage of 687 million units). Twelve of 30 (40%) patients had an
      antiviral response at 6 months after therapy. Clinical data before treatment in
      both responders and non-responders were comparable. Although not significant,
      responders tended to have younger age, a higher serum transaminase level, a lower
      frequency of precore mutation (G1896A) (67% vs. 92%) and a higher frequency of
      core promoter mutation (A1762T/G1764A) (89% vs. 58%) than non-responders. The
      patients treated long-term responded significantly better than those treated
      short-term (83% vs. 29%, P=0.026). Up to 12 years after therapy, a higher
      percentage of responders than non-responders had sustained clearance of HBeAg
      with seroconversion and normalization of transaminase concentration at the
      followed end point (83% vs. 17%, P<0.001). Two non-responder patients had
      cirrhosis after long-term follow-up. One non-responder patient died of
      hepatocellular carcinoma 8 years after IFN therapy; except in this patient there
      was no development of decompensated cirrhosis. Early responsiveness to IFN alpha
      therapy in Japanese patients with chronic active HBV genotype C infection
      improves the long-term clinical outcome.

PMID- 14654975
TI  - Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of
      endothelial cells.
AB  - Silibinin, the flavonoid found in the milk thistle, has been shown to suppress
      cell growth and exhibit anti-cancer effects. Some flavonoids were reported to
      inhibit angiogenesis which is essential for tumor growth and metastasis. In this
      study, to clarify the underlying mechanisms for the anti-cancer effect of
      silibinin, we examined the effects of silibinin on human endothelial ECV304
      cells. Silibinin was found to suppress the growth and induce the apoptosis of
      ECV304 cells. The induction of apoptosis by silibinin was confirmed by ladder
      patterned DNA fragmentation, cleaved and condensed nuclear chromatin and DNA
      hypoploidy. Silibinin could effectively inhibit constitutive NF-kappaB activation
      as revealed by electrophoretic mobility shift assay and NF-kappaB-dependent
      luciferase reporter study. Consistent with this, silibinin treatment resulted in
      a significant decrease in the nuclear level of p65 subunit of NF-kappaB. In
      addition, silibinin treatment caused a change in the ratio of Bax/Bcl-2 in a
      manner that favors apoptosis. Silibinin also induced the cytochrome c release,
      activation of caspase-3 and caspase-9 and cleavage of PARP. These results suggest
      that silibinin may exert, at least partly, its anti-cancer effect by inhibiting
      angiogenesis through induction of endothelial apoptosis via modulation of NF
      kappaB, Bcl-2 family and caspases.

PMID- 14654976
TI  - Neuro-optic cell apoptosis and microangiopathy in KKAY mouse retina.
AB  - Diabetic retinopathy is one of the common complications of diabetes and is the
      leading cause for patients' visual dysfunction and sight loss. However, the
      mechanism of diabetic retinopathy is not clearly defined. The present study was
      undertaken to investigate neuroretinal apoptosis in different stages in a mouse
      model for type 2 diabetes mellitus and the mechanism of diabetic retinopathy.
      KKAY mouse with genetic diabetes, an animal model for type 2 diabetes, was used
      in this study. Mice were divided into a control group and a diabetic group. The
      mice in both groups were sacrificed at one month and three months, and the mouse
      eyeballs were used for making retinal histologic sections. We showed in this
      study that the apoptotic cell numbers for retinal neural cells in the ganglion
      cell layer were significantly greater in the diabetic group than in the control
      group (p<0.01), as determined by the TUNEL assay. In addition, many more
      apoptotic retinal neuronal cells were found in the retinal ganglion cell layer
      and medial part of the inner nuclear layer in the diabetic group when the mice
      were sacrificed at three months as compared to those sacrificed at one month
      (p<0.01). We also studied the ultrastructure of the retinal nerve cells and
      microvesseles by electron microscopy and demonstrated that the ultrastructure
      changes for retinal neural cells and retinal microangiopathy were observed in, as
      early as, the early stage of diabetes. These findings indicate that: i). retinal
      neuropathy and microangiopathy occur in the early stage of diabetes, ii).
      apoptosis may be an important mechanism through which retinal neurodegeneration
      is developed, and iii). both retinal neurodegeneration and retinal
      microangiopathy should be considered as the diabetic retinopathy.

PMID- 14654977
TI  - Promoter methylation status of multiple genes in brain metastases of solid
      tumors.
AB  - The aberrant methylation of the CpG island promoter regions acquired by tumor
      cells is one mechanism for loss of gene function. The high methylation rate for
      RB1 and death-associated protein-kinase gene (DAP-kinase) (60 and 90%,
      respectively) previously found in brain metastases suggests this mechanism could
      be non-randomly associated to tumor progression and metastasis. Thus, in addition
      to these two genes, we determined the methylation status of the genes p16INK4a,
      glutathione S-transferase P1 (GSTP1), O6-methylguanine DNA methyltransferase
      (MGMT), thrombospondin-1 (THBS1), p14ARF, TP53, p73, and tissue inhibitor of
      metalloproteinase 3 (TIMP-3), in 18 brain metastases of solid tumors, with
      methylation specific PCR. The metastases were derived from malignant melanoma
      (three cases), lung carcinoma (six cases), breast carcinoma (three cases),
      ovarian carcinoma (two cases) and one each from colon, kidney, bladder and
      undifferentiated carcinoma. We detected methylation levels in the tumor samples
      of 83% in p16INK4a, 72% in DAP-kinase, 56% in THBS1, 50% in RB1, 39% in MGMT, 33%
      in GSTP1 and p14ARF each, 22% in p73 and TIMP-3 each, and 11% in TP53. The
      methylation index (number of genes methylated/number of genes tested) varied
      between 0.1 and 0.6, with an average of 0.42, indicating that a high grade of
      gene methylation accumulates parallel to the tumor metastasis process. Our data
      suggest an important role for gene methylation in the development of brain
      metastases, primarily involving epigenetic silencing of DAP-kinase, THBS1 and the
      cell-cycle regulators RB1/p16INK4a.

PMID- 14654978
TI  - TGF-beta1 inhibits Fas-mediated apoptosis by regulating surface Fas and cFLIPL
      expression in human leukaemia/lymphoma cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a pleiotrophic cytokine that
      mediates differentiation, growth, and apoptosis. As a potent immunosuppressive
      agent, TGF-beta1 induces apoptosis in primary lymphocytes. However, it has been
      recognized that TGF-beta1 plays certain roles in development or progression of
      hematopoietic tumours via inhibition of Fas-mediated apoptotic cell death.
      Several studies have highlighted the mechanisms of TGF-beta1-induced Fas
      resistance and its contribution to aggressive tumour behavior. In this study, we
      have focused on the mechanisms by which TGF-beta1 protected leukaemia/lymphoma
      cells from Fas-mediated apoptosis. The presented study provides that TGF-beta1
      inhibited Fas-mediated apoptosis of leukaemia/lymphoma cells in two distinct
      pathways. First, TGF-beta1 reduced expression of surface Fas receptors by
      blockade of trafficking cytoplasmic Fas to the surface, which allowed the
      leukaemia cells to resist Fas-mediated cell death. However, total Fas levels
      including both surface and cytoplasmic Fas were not altered, indicating that
      forced degradation of Fas or transcriptional regulation was not involved. Second,
      TGF-beta1 up-regulated Fas signaling pathway inhibitor cFLIPL to block the pro
      caspase-8 cleavage and thus promoted survival of leukaemia/lymphoma cells. Our
      findings may partly explain why higher concentration of serum TGF-beta1 in cancer
      patient was related with poor prognosis.

PMID- 14654979
TI  - Edaravone, a newly developed radical scavenger, protects against ischemia
      reperfusion injury of the small intestine in rats.
AB  - Although edaravone (3-methyl-1-phenyl-pyrazolin-5-one), a newly developed radical
      scavenging agent, has been widely used for protection against ischemia
      reperfusion (I-R) injury in patients with cerebral infarction, its effects on
      gastrointestinal I-R injury have not been evaluated. In the present study, we
      examined the effects of edaravone on experimental intestinal I-R damage in rats.
      In male Wistar rats with and without edaravone treatment, intestinal damage was
      induced by clamping the superior mesenteric artery for 30 min, followed by
      reperfusion. Edaravone was administered via intravenous infusion at 5 min before
      reperfusion was achieved by removal of the clamp. The rats were sacrificed after
      60 min of reperfusion. Luminal protein and hemoglobin concentrations were
      measured as an index of mucosal injury and histological examination of
      hematoxylin and eosin-stained sections was performed. Thiobarbituric acid (TBA)
      reactive substances and tissue-associated myeloperoxidase (MPO) activity were
      measured in the mucosa as indicators of lipid peroxidation and neutrophil
      infiltration, respectively. The mucosal concentration of cytokine-induced
      neutrophil chemoattractant (CINC)-1 (a member of the IL-8 family) was determined
      by enzyme-linked immunosorbent assay (ELISA). Additionally, CINC-1 messenger RNA
      (mRNA) was measured by the reverse-transcription polymerase chain reaction (RT
      PCR). As a result, the levels of luminal protein and hemoglobin, TBA-reactive
      substances, and MPO activity were all increased significantly by I-R injury, and
      these increases were significantly inhibited by treatment with edaravone.
      Multiple erosions and bleeding were observed macroscopically after the small
      intestine was exposed to I-R injury, and these changes were inhibited by
      administration of edaravone. Microscopic I-R damage was also reduced by treatment
      with edaravone. CINC-1 protein and CINC-1 mRNA were both increased by I-R injury,
      while edaravone markedly reduced the levels of both protein and mRNA. In summary,
      these results suggest that edaravone can protect the small intestine against I-R
      injury by scavenging oxygen-derived free radicals.

PMID- 14654980
TI  - Diverse efficacy of vaccination therapy using the alpha-fetoprotein gene against
      mouse hepatocellular carcinoma.
AB  - Antitumor vaccination therapy approaches using naked plasmid DNA or recombinant
      viruses encoding tumor-associated antigens are currently in development. In the
      present study, we examined the therapeutic efficacy of vaccination using the
      mouse alpha-fetoprotein (AFP) gene in mouse hepatocellular carcinoma (HCC) cells.
      C57L/J or C3H/HeN mice were primed with an injection of naked plasmid DNA
      expressing mouse AFP followed by a booster of replication-defective adenovirus
      expressing mouse AFP (plasmid-AFP prime/adenovirus-AFP booster vaccination). The
      mice were then challenged with high AFP-producing Hepa1-6 cells or low AFP
      producing MH134 cells, respectively, and the tumor growth rate was monitored.
      Plasmid-AFP prime/adenovirus-AFP booster vaccination promoted protective immunity
      against Hepa1-6 cells, and significantly increased the number of interferon-gamma
      producing splenic cells in C57L/J mice. In addition, this vaccination protocol
      repressed the growth of pre-established Hepa1-6 tumors in C57L/J mice. However,
      plasmid-AFP prime/adenovirus-AFP booster vaccination did not induce protective
      immunity against MH134 cells in C3H/HeN mice. These results suggest that
      vaccination with the AFP gene is a promising strategy to treat HCC, but its
      outcome may be affected by the level of AFP expression in HCC or by the
      immunological response of the host.

PMID- 14654981
TI  - Activity of synthetic enzymes of tetrahydrobiopterin in the human placenta.
AB  - Tetrahydrobiopterin (BH4) is an essential co-factor for nitric oxide (NO)
      synthase (NOS) and regulates the production of NO, or endothelium-derived
      relaxation factor. Although NOS is highly expressed in the placenta and NO plays
      a critical role in the regulation of feto-placental circulation, the mechanism
      maintaining the level of BH4 is not known. To investigate the de novo synthesis
      of BH4 in the human placenta, the activity of guanosine triphosphate
      cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and
      sepiapterin reductase (SR) in the chorionic tissue during the first, second and
      third trimester of pregnancy was analyzed. GTPCH activity was the lowest of the
      three enzymes and became negligible after the second trimester. There was no
      significant change in PTPS activity throughout pregnancy. Although SR activity
      decreased significantly after the second trimester, the levels remained abundant
      throughout pregnancy. These results showed that GTPCH is a rate-limiting enzyme
      and the total activity of the de novo synthesis of BH4 is negligible in the
      mature placenta after the second trimester when fetal growth is accelerated. The
      present study suggests that the level of BH4 in the placenta depends principally
      on the system other than de novo synthesis. The salvage pathway is considered the
      most potent system, which is formed by the transfer of the substrates from the
      fetus and their enzymatic conversion to BH4 in the placenta.

PMID- 14654982
TI  - Intracellular domain generation of amyloid precursor protein by epsilon-cleavage
      depends on C-terminal fragment by alpha-secretase cleavage.
AB  - A significant accumulation of Abeta is major pathological feature in the brain in
      patients with Alzheimer's disease (AD). Amyloid precursor protein (APP) is
      cleaved by alpha- and beta-secretase, resulting in secretion of extracellular
      domain. Then the remaining membrane-anchored C-terminal fragments (CTFalpha or
      CTFbeta) are cleaved by gamma-secretase. Therefore, Abeta is derived from APP by
      sequential proteolytic processing involving 2 proteases, called beta- and gamma
      secretase. Gamma-secretase cleavage results in the generation of the APP
      intracellular domain (AICD), as well as Abeta. Recently, AICD is generated by
      epsilon-cleavage site near the cytoplasmic membrane boundary of APP, not by gamma
      cleavage site in the middle of transmembrane domain. We show that elevated beta
      secretase levels induced the increase in CTFbeta and Abeta generation and
      reduction of CTFalpha and AICD generation in vitro. Furthermore, elevated alpha
      secretase levels induced an increase of AICD. The results suggest that generation
      of AICD by epsilon-cleavage depends on CTFalpha and that gamma- and epsilon
      cleavage are differentially regulated.

PMID- 14654983
TI  - Urinary extracellular matrix measurement as a reliable and cost effective
      diagnostic tool for bladder tumors.
AB  - Although numerous markers for bladder tumor (BT) have been investigated, a more
      effective, less expensive test is needed. To address this issue, we examined the
      urinary extracellular matrix (U-ECM) measurement in urine from patients with BT,
      and investigated the U-ECM measurement and its correlation with tumor grade and
      invasion. We also investigated the U-ECM measurement to ascertain the condition
      of the bladder wall injured by transurethral resection of bladder tumor (TUR-bt).
      Fresh urine samples were obtained from 170 patients with BT, 38 patients with
      chronic cystitis (CC) and 50 with normal bladder (NB). U-ECM measurements were
      higher in BT groups than in CC and in NB groups. There was no significant
      difference in the U-ECM measurement between grades. However, in another
      comparison between stages, U-ECM measurements were higher in advanced cancer than
      in early stage cancer. After surgery, U-ECM concentration increased on day 1 and
      levels of U-ECM that were higher prior to TUR-bt continued to increase until day
      6. U-ECM continued to decrease after day 6 and reached normal range on day 14.
      Our results demonstrated that measurement of U-ECM is a highly efficient,
      reliable and cost effective marker for screening and monitoring bladder tumors
      and is also a beneficial diagnostic tool. Evaluation of the results is relatively
      simple and accurate and the running cost of measuring U-ECM is significantly
      lower than other tests.

PMID- 14654984
TI  - Possible involvement of nuclear factor-kappaB inhibition in the renal protective
      effect of oral adsorbent AST-120 in a rat model of chronic renal failure.
AB  - Oral adsorbent, AST-120 removes uremic toxins (such as indoxyl sulfate) and
      retards the progression of chronic renal failure (CRF). However, its mechanism of
      action has not been precisely clarified. Since indoxyl sulfate elicits renal
      tubular nuclear factor-kappaB (NF-kappaB) activation in vitro, the present
      experiments were conducted to elucidate the involvement of NF-kappaB in the
      beneficial effects of AST-120 using rats with 3/4 nephrectomy, a model of early
      stage CRF. Daily administration of AST-120 was started at 6 weeks after 3/4
      nephrectomy and continued for 18 weeks. Sham-operated rats, untreated CRF rats
      and AST-120-treated CRF rats were compared for NF-kappaB DNA-binding activity,
      gene expression and renal histology. Systolic blood pressure was increased in CRF
      rats, and this increase was not affected by AST-120. Blood urea nitrogen, serum
      creatinine and urinary protein were increased in CRF rats. Although AST-120
      attenuated these increases, it did not do so to a statistically significant
      extent. Indoxyl sulfate, which was accumulated in serum of CRF rats, was
      significantly eliminated by AST-120. Renal cortical NF-kappaB DNA-binding
      activity was increased in CRF rats. AST-120 significantly inhibited this
      increase. Monocyte/macrophage infiltration and increased monocyte chemoattractant
      protein-1 (MCP-1) mRNA observed in CRF rats were attenuated by AST-120.
      Furthermore, AST-120 significantly blocked renal fibrosis with concomitant
      inhibition of transforming growth factor beta1 (TGF-beta1) gene expression. It
      appeared that AST-120 reduced NF-kappaB activation and possibly the activity of
      NF-kappaB-dependent pathways of interstitial inflammation including MCP-1
      expression and macrophage infiltration. The anti-inflammatory effect of AST-120
      mediated via inhibition of NF-kappaB is a possible mechanism by which AST-120
      retards the progression of renal fibrosis in CRF.

PMID- 14654985
TI  - Effects of leptin and leptin fragments on steroid secretion and proliferative
      activity of regenerating rat adrenal cortex.
AB  - Leptin, an adipose tissue-secreted hormone, acts via several isoforms of specific
      receptors (Ob-Rs), which may variously interact with the native leptin molecule
      and its fragments. Evidence has been provided that leptin affects rat adrenal
      functions, but the results were rather conflicting depending on the experimental
      condition examined (e.g. regenerating vs. mature or immature adrenal gland).
      Hence, we investigated the effects of three subcutaneous injections of murine
      leptin(1-147) and several leptin fragments (3 nmol/100 g body weight; 28, 16 and
      4 h before the sacrifice) on the secretory activity and growth of regenerating
      rat adrenal cortex. The following leptin fragments were tested: murine leptin(116
      130), and human leptin fragments 150-167, 138-167, 93-105, 22-56 and [Tyr]26-39.
      Leptin(1-147) enhanced plasma concentration of both aldosterone and
      corticosterone. The blood level of aldosterone was raised by leptin(116-130),
      leptin(138-167) and leptin(93-105), and that of corticosterone by leptin(93-105)
      and Tyr-leptin(26-39). Metaphase index (stachmokinetic method with vincristine)
      was unaffected by leptin(1-147), and lowered by leptin(116-130), leptin(150-167)
      and leptin(138-167). Collectively, our findings allow us to conclude that leptin
      and leptin fragments enhance the secretory activity and inhibit the growth of
      regenerating rat adrenal cortex, the biological activity of leptin being located
      in the C-terminal segment of its molecule.

PMID- 14654986
TI  - EGF mediates multiple signals: dependence on the conditions.
AB  - Epidermal growth factor (EGF) has been reported to both increase and decrease
      proliferation and apoptosis. In KB cells, EGF-induced alteration in proliferation
      and apoptosis are concentration and time dependent. High concentrations of EGF
      (10(-7) and 10(-8) M) stimulated proliferation and inhibited apoptosis at 24 h,
      with apoptosis increasing with prolonged exposure. Low concentrations of EGF (10(
      10)-10(-11) M) inhibited apoptosis without affecting proliferation. EGFR protein
      expression was downregulated at high and upregulated at low EGF concentrations.
      Significant inverse correlation was shown between EGFR expression level and
      apoptosis. These results suggest the EGF receptor involvement in the modulation
      of apoptosis and the role of EGF anti-apoptotic effects in EGF-induced apoptosis.

PMID- 14654987
TI  - Ethanol stimulates proliferation, ERalpha and aromatase expression in MCF-7 human
      breast cancer cells.
AB  - It is well documented that alcohol is associated with an increased risk factor
      for breast carcinogenesis although the underlying mechanisms are not clearly
      understood. It has been reported that in vitro, the culture of estrogen receptor
      (ER) expressing breast cancer cells in ethanol containing medium was associated
      with an increase in the proliferation rate, in the ERalpha content as well as in
      ER transcriptional activity. Since these changes are not observed in ER negative
      breast cancer cells, and since alcohol intake has been associated to an increased
      level of circulating estrogens, we have postulated that aromatase expression
      could be increased following ethanol exposure. The results of our studies show a
      1.3-fold increase in cell proliferation after 6 days of culture of MCF-7 cells in
      the presence of 0.1% ethanol. This enhanced proliferation is confirmed by the use
      of clonogenic assays which show a 1.5-fold increase in clonal growth in the
      presence of 0.1% ethanol. No statistically significant changes were observed in
      the presence of higher ethanol concentration (0.3%). After a 6-day exposure to
      0.1% ethanol, RT-PCR analyses reveal a 1.7-fold increase in ERalpha mRNA that was
      not significant, whereas western blot analyses show a significant 3.3-fold
      increase in ERalpha content. At the same stage, RT-PCR studies demonstrate a 2.4
      fold increase in aromatase mRNA level which is confirmed at the protein level by
      western blots performed after immuno-precipitation of the enzyme. Taken together,
      these results are in agreement with the involvement of ER signalling in ethanol
      induced stimulation of breast cancer cell proliferation and could help to
      understand why alcohol consumption is associated with breast cancer risk.

PMID- 14654988
TI  - Identification and characterization of human FNBP1L gene in silico.
AB  - FNBP1/FBP17/Rapostlin and TRIP10/CIP4 are structurally related microtubule
      binding proteins involved in the regulation of cell shape, polarity, motility,
      and signal transduction. Here, we identified and characterized the FNBP1-like
      (FNBP1L) gene by using bioinformatics. Human FLJ20275 (NM_017737.1) and mouse
      2610318I01Rik (NM_153118.1) were 5'-truncated partial cDNAs derived from human
      FNBP1L gene and mouse Fnbp1l gene, respectively. Exons 1-7 of FNBP1L gene were
      located within human genome sequence AL512651.13, and exons 7-15 within
      AL109613.11. Complete coding sequence of FNBP1L was determined in silico by
      assembling nucleotide sequences of FNBP1L exons. FNBP1L (547 aa) showed 59.4 and
      55.4% total-amino-acid identity with FNBP1 and TRIP10, respectively. FNBP1L,
      FNBP1 and TRIP10 shared the common domain structure, consisting of FCH, FBH, HR1
      and SH3 domains. FCH domain of FNBP1 family proteins is the microtubule-binding
      domain. HR1 (also known as antiparallel coiled-coil finger) is the binding domain
      for Rho family proteins, such as ARHN/RhoN and CDC42. SH3 domain of FNBP1 family
      proteins interacts with proline-rich region of Formin and WASP family proteins.
      FNBP1L gene was linked to SH2D3B/BCAR3 gene in tail-to-tail manner with an
      interval less than 8 kb within the human genome. FNBP1L-SH2D3B locus at human
      chromosome 1p22.1 was paralogous to GPR108-TRIP10-SH2D3A locus at 19p13.3 and
      GPR107-FNBP1-SH2D3C locus at 9q34.11-q34.13. This is the first report on
      comprehensive characterization of FNBP1L, which is predicted to function as a
      scaffold protein for microtubule, Rho family proteins, Formin-homology proteins
      and WAPS family proteins.

PMID- 14654989
TI  - GP7 can induce apoptotic DNA fragmentation of human leukemia cells through
      caspase-3-dependent and -independent pathways.
AB  - GP7 (4-[4"-(2",2",6",6"-tetramethyl-l"-piperidinyloxy)amino]-4'-demethyl
      epipodophyllotoxin), a new spin-labeled derivative of podophyllotoxin, is a
      promising anticancer drug of podophyllotoxin class. The primary effect of GP7 is
      the anticancer activity on transplanted mouse tumors and cultured tumor cells.
      However, its molecular mechanism of action is still obscure. In this study, we
      investigated the activity of GP7 to induce apoptosis in human leukemia HL-60 and
      Jurkat cells. Apoptosis was determined by detection of DNA fragmentation in
      agarose gel electrophoresis. GP7 induced apoptotic DNA fragmentation of HL-60 and
      Jurkat cells in time- and dose-dependent manner. We further investigated the
      activity of caspase-3 in GP7-induced apoptotic DNA fragmentation of HL-60 and
      Jurkat cells. GP7 also induced time- and dose-dependent caspase-3 activation in
      both cell lines, and the kinetics of caspase-3 activation induced by GP7 was well
      correlated with that of apoptotic DNA fragmentation. To determine the role of
      caspase-3 in GP7-induced apoptotic DNA fragmentation, we examined the effect of
      specific caspase-3 inhibitor, Ac-DEVD-CHO, on GP7-induced apoptotic DNA
      fragmentation. Ac-DEVD-CHO prevented GP7-induced caspase-3 activation in both HL
      60 and Jurkat cells, however, it only inhibited GP7-induced apoptotic
      internucleosomal DNA fragmentation in HL-60 cells. We then employed L-carnitine
      to investigate the role of caspase-3 in GP7-induced apoptotic DNA fragmentation.
      L-carnitine treatment prevented GP7-induced caspase-3 activation in both cell
      lines in a dose-dependent manner. Similar to Ac-DEVD-CHO, L-carnitine only
      inhibited GP7-induced apoptotic internucleosomal DNA fragmentation in HL-60
      cells. These findings suggest that GP7 exerts an anti-leukemic effect by both
      caspase-3-dependent and -independent apoptotic signaling pathways.

PMID- 14654990
TI  - Gleditsia sinensis fruit extract induced growth inhibition involves basic
      fibroblast growth factor and nitric oxide.
AB  - Recently we have shown the antiproliferative activity of Gleditsia sinensis fruit
      extract (GSE) on various solid tumour and leukaemia cell lines as well as primary
      cultured bone marrow cells isolated from patients with acute and chronic
      myelogenous leukaemia. We further studied whether the growth inhibitory effect of
      GSE involves basic fibroblast growth factor (bFGF) in cancer cell lines including
      breast cancer MDA-MB231, nasopharyngeal cancer CNE-2 and prostate cancer LNCaP.
      We also investigated whether GSE could alter the production of nitric oxide (NO)
      pattern from these cancer cell lines. Growth inhibition assay was quantitated by
      sulforhodamine B protein staining method. Enzyme linked immunosorbent assay
      (ELISA) was used to quantitate the total bFGF protein. The amount of NO secreted
      into culture medium in terms of nitrite ion concentration was measured by the
      Greiss method. ELISA showed that GSE could stimulate total bFGF protein level
      which was dose- dependent. NO production was also stimulated from these cancer
      cell lines after treating with GSE. Both of the increment in total bFGF and NO
      levels were correlated with the degree of growth inhibition. Changes involving
      cell shrinkage and detachment of cancer cells could readily be observed. Taken
      together, our results here suggest that growth inhibition induced by GSE in these
      solid tumour cell lines may involve both bFGF and NO regulations.

PMID- 14654991
TI  - Surface carbohydrates as recognition determinants in non-opsonic interactions and
      intracellular viability of group B Streptococcus strains in murine macrophages.
AB  - Mononuclear cells have been found to play a key role in phagocytosis and eventual
      killing of group B streptococci (GBS). The rich array of sugars on bacterial
      surface plus the presence of membrane-associated lectin-receptors on the
      macrophage suggests that this is a likely means for GBS recognition by these host
      defense cells. Macrophages have been shown to bind GBS in the absence of serum
      components. However, participation of carbohydrate moieties in GBS intracellular
      survival had not been completely elucidated. The aim of this study was to assess
      the involvement of sugars on adherence and intracellular viability in murine
      macrophages of GBS serotypes Ia (85147 and 90222 strains), III (80340 and 90356
      strains) and V (88641 and 90186 strains) isolated from assymptomatic carriers and
      patients, respectively. Most isolates showed higher adherence within 2-h
      incubation. Only 90222-Ia strain exhibited progressive adherence rate until 12-h
      incubation. All strains showed intracellular viability during first 0.5-h of
      incubation. Except for 90186-V strain that survived only for 2 h, strains of all
      serotypes tested were found to survive 24 h into macrophages. Treatments of
      bacteria by glycosidases inhibited macrophage interaction with GBS strains at
      varied levels. Neuraminidase inhibited 90-97% adherence and 100% intracellular
      survival of GBS strains (P<0.0001). Host cell treatments with Rhamnose, N-acetyl
      D-glucosaminidase and Fucose (5 mg/ml) inhibited adherence and intracellular
      viability of GBS strains at varied levels. Removal of GlcNAc residues of invasive
      GBS isolates enhanced intracellular viability, suggesting that GlcNAc residues
      may act by intercepting the expression of hidden receptors probably related with
      invasiveness and survival within macrophages. Lastly, our results demonstrate
      involvement of sialic acid specific receptors on macrophages and
      lectinophagocytosis in non-opsonic interaction and survival of GBS invasive
      isolates.

PMID- 14654992
TI  - Additive effect of TRAIL and p53 gene transfer on apoptosis of human lung cancer
      cell lines.
AB  - TRAIL is a cytokine that can induce tumor-specific apoptosis through its specific
      death receptors (DR4 and DR5) and p53 has been proven to increase the expression
      of death receptors. To examine their interaction in tumor suppression, p53 and
      TRAIL genes were inserted in recombinant adenovirus vectors and transferred
      simultaneously into non-small cell lung cancer cell lines (NCI-H157, NCI-H358,
      NCI-H460 and A549). Western blot assay demonstrated production of TRAIL protein
      in NCI-H157 and A549 cell lines. Increased expressions of DR4 and DR5 of NCI-H157
      and DR4 of A549 after p53 overexpression were confirmed by flow cytometry. p53 or
      TRAIL gene transfer increased sub-G1 fraction in cell cycle analysis and
      inhibited the tumor growth dose-dependently and the degree was potentiated by co
      transfer. But isobologram analysis indicated an additive effect. Together, these
      data indicate that p53 and TRAIL interact additively on tumor apoptosis despite
      theoretical synergism.

PMID- 14654993
TI  - Natural cell-mediated cytotoxicity of peripheral blood lymphocytes against target
      cells transfected with epidermodysplasia verruciformis-specific human
      papillomavirus type 8 L1 DNA sequences.
AB  - The aim of the present study was to characterise natural cell-mediated
      cytotoxicity against COS-7 cells transfected with potentially oncogenic HPV-8 L1
      DNA sequences cloned in sense and antisense orientation and to evaluate their
      lysis by peripheral blood lymphocytes (PBL) from patients with epidermodysplasia
      verruciformis (EV), a rare disease associated with life-long infection by
      specific HPV types. COS-7 cells were transfected with HPV-8 Hinc II restriction
      fragment (nucleotide positions 5434-7654) cloned in sense (COS-L1S) and antisense
      (COS-L1A) orientation into pCB6 expression vector. Cytotoxic activity of isolated
      PBL against COS cell lines as well as K562 erythroleukaemic cells was evaluated
      by 51Cr-release assay. We found that lymphocytes responsible for natural lysis of
      COS and K562 cells are CD3-negative CD56-positive natural killer (NK) cells.
      Analysis of NK cell cytotoxic activity against different COS cell lines has
      revealed that lymphocytes from healthy subjects killed COS-L1S cells
      significantly more efficiently than wild COS-7 and COS-L1A cells. Significantly
      more efficient lysis of COS-L1S cells was also observed in EV patients. Thus,
      expression of HPV L1 renders target cells more susceptible to NK-mediated
      cytotoxicity that may enable more effective elimination of transformed cells.

PMID- 14654994
TI  - Molecular cloning and characterization of a novel human BTBD8 gene containing
      double BTB/POZ domains.
AB  - BTB/POZ domain is an evolutionarily conserved protein-protein interaction domain
      often found in developmentally regulated transcription factors. Previous studies
      have shown that many additional conserved motifs have been found in association
      with BTB/POZ domain, including kelch repeats, zinc finger domains, FYVE fingers
      and ankyrin repeats. Here we report a novel human gene containing double BTB/POZ
      domains, named BTBD8 in agreement with the HUGO Nomenclature Committee. The cDNA
      sequence contains an open reading frame of 918 bp encoding a putative protein of
      305 amino acid residues with a predicted molecular mass of 34.6 kDa. Protein
      pattern analysis shows that it contains double BTB/POZ domains. Weak expression
      was detected in adult brain and prostate of the 16 adult tissues examined, while
      it had a more abundant expression pattern in human fetal brain. The expression
      pattern of BTBD8 shows it may have a function related to brain development.

PMID- 14654995
TI  - Connections between the anterior inferotemporal cortex (area TE) and CA1 of the
      hippocampus in monkey.
AB  - In addition to the trisynaptic perforant pathway from entorhinal cortex to CA1,
      there are multiple direct parallel pathways between several cortical regions and
      CA1. These may be supposed to function cooperatively, in conjunction with the
      perforant pathway; but neither the functional nor anatomical organization of the
      extended network is well understood. In this report, we further investigate the
      connections between anterior inferotemporal cortex (area TE) and CA1. Injections
      of tracer substances demonstrate that part of the dorsal subdivision of TE sends
      projections to CA1, but does not receive reciprocating projections back. This
      contrasts with the bi-directional connections between the more ventral
      subdivision, TEav, and CA1, as reported by previous studies (and corroborated by
      tracer injections in this report). The corticohippocampal projections from dorsal
      TE are likely to be unimodal visual. They partially converge in the posterior
      portion of CA1 with connections from posterior TE and from the inferior parietal
      lobule, perhaps constituting a network related to visual or visuospatial
      processes.

PMID- 14654998
TI  - Early intervention in schizophrenia: three frameworks for guiding ethical
      inquiry.
AB  - Psychiatric research is making important strides toward early detection and
      treatment of schizophrenia. Discovery of genetic markers, identifiable prodromes,
      and low-risk interventions fuel this vital scientific movement. At the same time,
      investigators and clinicians are studying the ethical questions that arise
      whenever the bounds of diagnosis and treatment are evolving rapidly. This ethical
      analysis generally falls within three dominant frameworks of bioethics: the
      conceptualization of disease, scientific uncertainty, and risk-factor ethics.
      These frameworks are explored as potential guides for directing ethical inquiry
      in early intervention.

PMID- 14654996
TI  - Sex differences in the acquisition of IV methamphetamine self-administration and
      subsequent maintenance under a progressive ratio schedule in rats.
AB  - RATIONALE: Previous work indicates that female rats initiate cocaine use sooner
      than male rats and reach significantly higher break points (BPs) for a single
      injection of cocaine under a progressive ratio (PR) schedule compared to male
      rats. OBJECTIVES: The present study extends previous work examining sex
      differences to the acquisition of methamphetamine (METH) (0.02 mg/kg) and
      maintenance of METH-maintained responding under a PR schedule. METHODS: An
      automated priming procedure that has previously been shown to be sensitive to sex
      differences was used for the acquisition of drug self-administration. A PR
      schedule that has been shown to be sensitive in detecting sex differences in
      maintenance levels of cocaine-reinforced responding was used for the maintenance
      phase of the experiment. RESULTS: A greater percentage of female rats met the
      acquisition criterion for METH (0.02 mg/kg) self-administration compared to male
      rats (55.6% versus 11.1%, respectively), and they did so at a significantly
      faster rate. Under stable fixed-ratio 1 (FR1) conditions (after acquisition and 5
      days before the PR schedule) female rats responded for significantly more METH
      (0.02 mg/kg) infusions compared to males. Dose-response curves obtained under the
      PR schedule during maintenance indicated that female rats self-administered
      significantly more METH infusions compared to male rats. CONCLUSIONS: These data
      suggest that female rats are more vulnerable to the acquisition of METH self
      administration, and they are more motivated to self-administer METH compared to
      male rats under a PR schedule during the maintenance phase.

PMID- 14655000
TI  - Phylogenetic and physiological characterization of a filamentous anoxygenic
      photoautotrophic bacterium ' Candidatus Chlorothrix halophila' gen. nov., sp.
      nov., recovered from hypersaline microbial mats.
AB  - We report the phylogenetic and physiological characterization of a mesophilic and
      halophilic member of the filamentous anoxygenic phototrophic (FAP) bacteria,
      provisionally named ' Candidatus Chorothrix halophila' gen. nov. sp. nov., that
      has been maintained in a highly enriched culture in our laboratory for over a
      decade. Phylogenetic analysis of small-subunit RNA-encoding sequences places '
      Candidatus Chlorothrix halophila' in a clade that includes cultivated members of
      the genera Chloroflexus and Oscillochloris. Physiological studies demonstrated
      sulfide-dependent photosynthetic uptake of (14)C-labeled bicarbonate. Enzymatic
      assays for the activity of propionyl-coenzyme A synthase indicated that '
      Candidatus Chlorothrix halophila' does not use the 3-hydroxypropionate cycle of
      Chloroflexus aurantiacus OK-70-fl for autotrophic carbon assimilation. New
      concepts regarding the taxonomy and phylogeny of FAP bacteria have emerged from
      this work.

PMID- 14654999
TI  - Xanthine nucleotide-specific G-protein alpha-subunits: a novel approach for the
      analysis of G-protein-mediated signal transduction.
AB  - Pro- and eukaryotic cells express multiple GTP-binding proteins that play crucial
      roles in signal transduction. GTP-binding proteins possess a highly conserved NKX
      D motif critically involved in guanine binding. In order to selectively activate
      a defined GTP-binding protein, base-specificity can be switched from guanine to
      xanthine by mutating the conserved aspartate into asparagine (D/N-mutation). This
      approach was very successful at elucidating the function of structurally diverse
      GTP-binding proteins in complex systems. However, attempts to generate functional
      xanthine nucleotide-specific alpha-subunits of heterotrimeric GTP-binding
      proteins (G-proteins) met more difficulties. Recent studies have shown that a
      sufficiently high GDP-affinity is critical for functional expression of xanthine
      nucleotide-selective G-protein mutants. Moreover, xanthosine 5'-[gamma
      thio]triphosphate and xanthosine 5'-[gamma, beta-imido]triphosphate are not
      functionally equivalent activators of D/N-G-protein mutants. We are now in the
      position to exploit xanthine nucleotide-specific G-proteins to dissect signaling
      pathways activated by a given G-protein in complex systems.

PMID- 14655001
TI  - Glucose-6-phosphate isomerase from the hyperthermophilic archaeon Methanococcus
      jannaschii: characterization of the first archaeal member of the phosphoglucose
      isomerase superfamily.
AB  - ORF MJ1605, previously annotated as pgi and coding for the putative glucose-6
      phosphate isomerase (phosphoglucose isomerase, PGI) of the hyperthermophilic
      archaeon Methanococcus jannaschii, was cloned and functionally expressed in
      Escherichia coli. The purified 80-kDa protein consisted of a single subunit of 45
      kDa, indicating a homodimeric (alpha(2)) structure. The K(m) values for fructose
      6-phosphate and glucose 6-phosphate were 0.04 mM and 1 mM, the corresponding
      V(max) values were 20 U/mg and 9 U/mg, respectively (at 50 degrees C). The enzyme
      had a temperature optimum at 89 degrees C and showed significant thermostability
      up to 95 degrees C. The enzyme was inhibited by 6-phosphogluconate and erythrose
      4-phosphate. RT-PCR experiments demonstrated in vivo expression of ORF MJ1618
      during lithoautotrophic growth of M. jannaschii on H(2)/CO(2). Phylogenetic
      analyses indicated that M. jannaschii PGI was obtained from bacteria, presumably
      from the hyperthermophile Thermotoga maritima.

PMID- 14655002
TI  - The importance of porE and porF in the anabolic pyruvate oxidoreductase of
      Methanococcus maripaludis.
AB  - The operon of the anabolic pyruvate oxidoreductase (POR) of Methanococcus
      maripaludis encodes two genes ( porEF) whose functions are unknown. Because these
      genes possess sequence similarity to polyferredoxins, they may be electron
      carriers to the POR. To elucidate whether the methanococcal POR requires PorEF
      for activity, a deletion mutant, strain JJ150, lacking porEF was constructed.
      Compared to the wild-type strain JJ1, the mutant grew more slowly in minimal
      medium and minimal plus acetate medium, and pyruvate-dependent methanogenesis was
      inhibited. In contrast, the methyl-viologen-dependent pyruvate-oxidation activity
      of POR, carbon monoxide dehydrogenase, and hydrogenase activities of the mutant
      were similar to those of the wild-type. Upon genetic complementation of the
      mutant with porEF in the methanococcal shuttle vector pMEV2+ porEF, growth in
      minimal medium and pyruvate-dependent methanogenesis were restored to wild-type
      levels. Complementation with porE alone restored methanogenesis from pyruvate but
      not growth in minimal medium. Complementation with porF alone partially restored
      growth but not methanogenesis from pyruvate. Although the specific roles of porE
      and porF have not been determined, these results suggest that PorEF play
      important roles in the anabolic POR in vivo even though they are not required for
      the dye-dependent activity.

PMID- 14655003
TI  - [Evidence-based antibiotic prophylaxis in aseptic orthopedic surgery].
AB  - Disagreement exists on the topic of antibiotic prophylaxis in aseptic orthopedic
      surgery. No evidence on the usefulness of prophylactic antibiotic administration
      exists with regard to non-complex aseptic surgeries without placement of
      osteosynthetic material. Likewise, no undisputed evidence exists on the
      usefulness of antibiotic prophylaxis with regard to aseptic orthopedic surgeries
      involving placement of osteosynthetic material. However, the majority of experts
      agree on antibiotic prophylaxis in the latter cases. In contrast clear evidence
      does exist regarding the usefulness of antibiotic prophylaxis with first- or
      second-generation cephalosporins for surgeries of the hip involving fracture
      treatment or prosthetic replacement. The prophylactic use of glycopeptides should
      be confined to cases of high MRSA or MRSE risk. Administration of prophylactic
      antibiotics should precede incision time by around 30 min and tourniquet
      inflation by at least 10 min. Antibiotic administration may be repeated in the OR
      when surgery lasts longer than 3 h. The use of local antibiotics in bone cement
      has not proven useful as a prophylactic measure.

PMID- 14655004
TI  - [Clinical pharmacology of the selective COX-2 inhibitors].
AB  - The discovery of two isoforms of cyclooxygenases (COX-1 and COX-2) has provided a
      new insight into the involvement of prostaglandins in the clinical effectiveness
      and gastrointestinal toxicity of NSAIDs. Currently, there are four selective COX
      2 inhibitors available in Germany: celecoxib, rofecoxib, valdecoxib and
      parecoxib. Orally administered rofecoxib, celecoxib and valdecoxib have been
      approved for the relief of symptoms of osteoarthritis and rheumatoid arthritis.
      Parecoxib, the first selective COX-2 inhibitor for parenteral administration, has
      been approved for the short-term treatment of post-operative pain. The clinical
      efficacy of the marketed COX-2 inhibitors has been proved in large phase III
      clinical trials in comparison to both placebo and classical NSAIDs (e.g.
      diclofenac, naproxen). The incidence of gastrointestinal complications was
      significantly lower than that with the non-selective NSAIDs. However, the
      clinical relevance of these effects was, at least in some populations of patients
      (e.g. patients on low dose aspirin), not as high as initially expected. While not
      replacing less expensive classical NSAIDs, selective COX-2 inhibitors provide a
      marked enrichment of the spectrum of anti-inflammatory and analgesic
      therapeutics.

PMID- 14655005
TI  - [Therapy with nonsteroidal anti-inflammatory drugs].
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently
      prescribed drugs worldwide. Their analgetic and antiphlogistic effect results
      from an efficient inhibition of prostaglandin synthesis. The risk of side effects
      is remarkable. This concerns namely side effects in the gastrointestinal tract
      and the kidneys. The common NSAIDs inhibit both isoforms of the cyclooxygenase
      (COX). The analgetic and antiphlogistic effect results from the inhibition of COX
      2, whereas the inhibition of COX-1 is responsible for the majority of side
      effects. If NSAID therapy is necessary, patients at risk should receive an
      effective prophylaxis, or be treated with COX-2-selective substances. The
      analgetic effects of COX-2 inhibitors are comparable to common NSAIDs, with a
      significant reduction of the gastrointestinal risks, except in cases of
      additional risk factors, e.g., low-dose ASS therapy, etc. In cases of renal
      impairment both substances should be used with caution, and subtle monitoring is
      necessary.

PMID- 14655006
TI  - [Drug therapy of rheumatoid arthritis].
AB  - Nowadays undisputed is the effectiveness of early and long-standing DMARD therapy
      in the presence of active rheumatoid arthritis on disease progression and
      avoidance of structural joint changes. "Early" is defined as immediate initiation
      of drug therapy after diagnosis of rheumatoid arthritis. "Long-term" refers to a
      mostly life-long therapy, which even in the case of remission should be continued
      for at least 1 year. Clinical and laboratory routine controls during DMARD
      therapy are absolutely necessary. "DMARDs" summarize disease-modifying
      antirheumatic drugs such as methotrexate, sulfasalazine, leflunomide,
      hydroxychloroquine, aurum but also the TNF-blockers infliximab and etanercept. In
      cases of disease remission with combination drug therapy, corticosteroids and
      NSAID should be discontinued in a timely manner ahead of DMARDs to ensure that
      the reduction of clinical symptoms is not steroid controlled. DMARD therapy
      should end at least 6 months prior to conception.

PMID- 14655007
TI  - [Therapy of postmenopausal osteoporosis].
AB  - The therapy of postmenopausal osteoporosis is based on a few comprehensible
      assumptions. High bone resorption should be reduced by treatment with
      bisphosphonates, raloxifene or seldom with calcitonins. After reduction of high
      bone turnover and in low bone turnover situations, an osteoinductive combination
      therapy should be started, inducing collagen type I with parathyroid hormone or
      fluorides. This collagen can then be mineralized by calcium, vitamin D, and
      vitamin D metabolites. In addition, bone resorption should be reduced during
      menopause with estrogens and gestagens, in the case of a receptor-positive breast
      cancer with tamoxifen, and after menopause with raloxifene or a bisphosphonate.
      In elderly patients a depletion of vitamin D often induces an osteoporomalacia
      instead of an osteoporosis. In this situation, mineralization of the osteoid by
      calcium and vitamin D is sufficient for therapy. A daily osteoporosis gymnastic
      program is required and physical activity should be enhanced to increase muscle
      mass because bone adapts to the individual situation.

PMID- 14655008
TI  - [Postoperative pain therapy in orthopedics].
AB  - Postoperative pain management adheres to the principles of a three-step routine
      according to the WHO recommendations. This routine suggests the combination of a
      basic non-opioid (step I) with an opioid of low potency (step II) or high potency
      (step III). Non-opioids are routinely administered prior to an opioid. While i.v.
      application is the treatment of choice in the immediate postoperative course, a
      switch to oral pain medication is preferred as early as possible. With oral
      opioid therapy preference should be given to slow release drugs. Intramuscular
      application of pain medication has little place in postoperative pain management.
      In order to lower the need for systemic pain medication, postoperative pain
      management is supplemented by regional anesthesia administered pre- or
      intraoperatively. Requirement for pain medication beyond normal or increasing
      with postoperative time is suggestive of a postsurgical complication. Among the
      numerous drugs available for postoperative pain management, the physician is
      advised to confine his selection of pain medication to a limited number in order
      to gain superior knowledge of effects and side effects of the drugs administered.

PMID- 14655009
TI  - [Drug therapy of back pain].
AB  - The importance of analgesic drugs in the treatment of low back pain is a matter
      of intense debate. Based on the current literature, a multidisciplinary approach
      combining drug treatment with physical and psychotherapy has proven to be the
      most successful treatment of back pain. This perspective is challenged by various
      anesthesiologists who claim that early use of opioids in back pain therapy is the
      concept of choice. The results of recent studies regarding this matter are
      controversial. This chapter reviews the historical background of analgetic drugs
      and provides an overview of the current diagnostic and therapeutic options in the
      treatment of back pain. Recommendations are given based on the results of current
      randomized controlled studies.

PMID- 14655010
TI  - [Intra-articular injection. Substances and techniques].
AB  - Intra-articular injections are widely used in the treatment of joint pain and/or
      inflammation. Low costs, effectiveness, and safety are offered as possible
      reasons. The method remains controversial, as the evidence supporting the
      efficacy of these procedures has been poor. To evaluate intra-articular therapy,
      a meta-analysis of the efficacy of various agents injected intra-articularly was
      performed. Furthermore, indications and medications are discussed.

PMID- 14655011
TI  - [Long-term results after conservative treatment of pediatric femoral shaft
      fractures].
AB  - The principles of treatment for fractures of the femoral shaft in children
      include conservative and operative management. Traditionally, these fractures
      have been treated conservatively with skeletal traction. More frequent
      consideration is being given to the psychological and economical outcome. At what
      age of the patient surgery can be performed is still open to debate. From 1988 to
      1999, 52 children with closed femoral shaft fractures were treated conservatively
      in the Klinik fur Unfallchirurgie, Plastische und Wiederherstellungschirurgie der
      Universitat Gottingen (until 1994 Klinik fur Allgemeinchirurgie). Overhead
      traction was applied in 27 children with a mean age of 19.9 months (group I), and
      a 90-90 skeletal traction was performed in 25 children with a mean age of 47
      months (group II). This treatment was followed by spica casting on an outpatient
      basis. At a mean follow-up of 6 11/12 years (2 4/12-12 5/12) in 33 children all
      fractures were healed and no malalignment with clinical relevance could be
      observed. In four patients the limb overgrowth was 15-20 mm. The assessment of
      psychological and somatic aspects revealed disturbances in the family
      environment. The average length of hospitalization was much shorter in group I
      (mean: 17.4 days) than in group II (mean: 23.7 days). Our study confirms the good
      long-term results after conservative treatment of femoral shaft fractures in
      children up to 6 years. Social and psychological problems due to the prolonged
      period of hospitalization as well as the high costs of skeletal traction favor
      surgical treatment for children older than 3-4 years.

PMID- 14655012
TI  - [Chronic recurrent multifocal osteomyelitis. Opinion exchange concerning the
      article by T. Seidl et al in Der Orthopade (2003) 32:535-540].

PMID- 14655013
TI  - The aetiology of paediatric inflammatory vulvovaginitis.
AB  - Vulvovaginitis is the most common gynaecological problem in prepubertal girls and
      clear-cut data on the microbial aetiology of moderate to severe infections are
      lacking. Many microorganisms have been reported in several studies, but
      frequently the paediatrician does not know the pathogenic significance of an
      isolate reported in vaginal specimens of girls with vulvovaginitis. A multicentre
      study was performed, selecting 74 girls aged 2 to 12 years old with a clinical
      picture of vulvovaginitis and inflammatory cells on Gram stain. All the specimens
      were cultured following standard microbiological techniques and the
      paediatricians completed a questionnaire to highlight risk factors after
      interviewing the parents or tutors. The data were compared with those obtained in
      a control group of 11 girls without vulvovaginitis attending a clinic.
      Streptococcus pyogenesand Haemophilus spp.were isolated in 47 and 12 cases,
      respectively. Upper respiratory infection in the previous month ( P<0.001) and
      vulvovaginitis in the previous year ( P<0.05) were identified as significant risk
      factors. Foreign bodies, sexual abuse, poor hygiene and bad socioeconomic
      situation were not identified as risk factors for the infection. CONCLUSION:
      Paediatric inflammatory vulvovaginitis is mainly caused by pathogens of the upper
      respiratory tract and the most common risk factor for this infection is to have
      suffered an upper respiratory tract infection in the previous month.

PMID- 14655014
TI  - Snail3 orthologues in vertebrates: divergent members of the Snail zinc-finger
      gene family.
AB  - Snail genes comprise a family of zinc-finger transcription factor coding genes
      with multiple roles in early embryonic development of metazoans. The evolutionary
      history of this family has been studied in detail, revealing an initial
      duplication in Snail and Scratch genes preceding the protostome/deuterostome
      split, and posterior independent duplication events in the lineages leading to
      insects and vertebrates. The distribution of mammalian and teleost Snail genes
      fits with current models for whole genome duplication events at the base of the
      vertebrate lineage, plus an extra duplication in teleosts. However, two very
      divergent Snail genes, one from mammals and the other from teleost fishes, fit
      poorly into the phylogenetic analysis of the family. By means of database mining
      and synteny analysis, we provide evidence for these genes being orthologues, and
      evidence that they originated in an early duplication at the base of the
      vertebrates resulting in three and not two Snail genes. We further show that all
      three Snail genes lie in regions of extensive paralogy, revealing their common
      origin through segmental or chromosomal duplication.

PMID- 14655015
TI  - Effects of brassinazole, an inhibitor of brassinosteroid biosynthesis, on light-
      and dark-grown Chlorella vulgaris.
AB  - Treatment of cultured Chlorella vulgaris Beijerinck cells with 0.1-10 microM
      brassinazole (Brz2001), an inhibitor of brassinosteroid (BR) biosynthesis,
      inhibits their growth during the first 48 h of cultivation in the light. This
      inhibition is prevented by the co-application of BR. This result suggests that
      the presence of endogenous BRs during the initial steps of the C. vulgaris cell
      cycle is indispensable for their normal growth in the light. In darkness, a
      treatment with 10 nM brassinolide (BL) promotes growth through the first 24 h of
      culture, but during the following 24 h the cells undergo complete stagnation.
      Treatment of dark-grown cells with either Brz2001 alone, or a mixture of 10 nM BL
      and 0.1/10 microM Brz2001, also stimulates their growth. The effects of treatment
      with 10 nM BL mixed with 0.1-10 microM of a mevalonate-pathway inhibitor
      (mevinolin), or a non-mevalonate-pathway inhibitor (clomazone), were also
      investigated. Mevinolin at these concentrations did not inhibit growth of C.
      vulgaris; however, clomazone did. Addition of BL overcame the inhibition. These
      results suggest that the mevalonate pathway does not function in C. vulgaris, and
      that the non-mevalonate pathway for isopentenyl diphosphate biosynthesis is
      responsible for the synthesis of one of the primary precursors in BR
      biosynthesis.

PMID- 14655017
TI  - EDETOX. Evaluations and predictions of dermal absorption of toxic chemicals.

PMID- 14655016
TI  - Marginal effects of regional intra-arterial chemotherapy as an alternative
      treatment option in advanced pancreatic carcinoma.
AB  - BACKGROUND: Locoregional intra-arterial (i.a.) chemotherapy may provide high
      levels of cytostatic concentrations within the tumour and, simultaneously, a low
      rate of systemic side effects compared with systemic administration of anti
      neoplastic drugs. In addition, this may lead to an increase of tumour response
      rate and prolongation of survival time. The aim of the study was (1) to evaluate
      the benefit of an i.a. infusion of cytostatic drugs via the coeliac trunk on
      tumour response rate and survival time, (2) to elucidate problems and risks, and
      finally (3) to achieve an improvement of overall therapeutic management in
      pancreatic carcinoma. PATIENTS AND METHODS: In 22 patients (12 female; 10 male;
      mean age 57.1 years) with locally advanced pancreatic carcinoma, which was
      confirmed by histopathology, i.a. chemotherapy was administered. Through a
      catheter, which was inserted via the femoral artery by the Seldinger technique
      and placed with the tip in the coeliac trunk, two different drug combinations
      were given. Group A ( n=12) were given a bolus injection of a mixture (chemo
      occlusion) consisting of amilomer (Spherex) and epirubicin (Farmorubicin)
      followed by short-time infusion of folic acid and 24-h infusion of 5-FU. Group B
      ( n=10) were given treatment over 5 days: mitoxantrone (Novantrone, day [d] 1), 5
      FU and folic acid (Haemato-folin, d 2-4), and cisplatin (d 5). Treatment was
      repeated in both groups every 4 weeks. Tumour response was assessed by computed
      tomography every 8 weeks. RESULTS: In group A, there was one complete and one
      partial remission, resulting in a remission rate of 16.6%. Two patients showed
      stable disease, while in two-thirds of the patients ( n=8), progressive disease
      was found. Median survival time was 3 months; 1-year survival rate was 33.3% (4
      of 12 patients). In group B, again, one complete and one partial remission were
      observed (remission rate 20%). In three cases, stable disease, and in 50% of
      patients ( n=5), progressive disease, were documented. Median survival was 7.0
      months; 1-year survival rate was 20% (2 of 10 patients). If both groups were
      compared, there was no difference in survival. In addition, no prolongation of
      survival time was found in comparison with patients of a historical study group
      treated with established systemic chemotherapy using gemcitabine monotherapy (
      n=28; median survival time 9 months). Though a tendency for poorer outcome of
      i.a. chemotherapy was seen when the Kaplan-Meier curves of survival were
      compared, this difference was not statistically significant (log rank test,
      P=0.08). CONCLUSION: Despite conceptual and pharmacokinetic advantages of
      locoregional i.a. chemotherapy, better outcome with regard to tumour response
      rate and survival time could not be found. I.a. chemotherapy is, therefore, still
      an experimental treatment option in pancreatic carcinoma and can, currently, not
      be recommended for routine use.

PMID- 14655018
TI  - Experimental study of a porous rat tracheal prosthesis made of T40: long-term
      survival analysis.
AB  - In order to repair large defects in the laryngotracheal area, we developed a
      biomaterial based on porous titanium (Ti40) formed of spherical particles that
      are welded together. These Ti40 beads were arranged in several layers to create
      the rat tracheal prosthesis. After a partial tracheal resection, the prosthesis
      was fixed to both extremities to replace the missing part. Tissue surrounding the
      prosthesis was collected from 33 surviving animals after an implantation period
      of 3 to 12 months. Histological analyses showed that the periphery of the
      prosthesis was covered with fibroblasts and a few lymphocytes that penetrated the
      titanium layers. A ciliary cylindrical epithelium of respiratory type was found
      on the endoluminal side. The inflammatory reaction observed was minimal. These
      data indicate that the prosthesis, implanted in a laryngotracheal environment, is
      well tolerated by animals. Our results represent the first step towards the
      construction of a total laryngeal prosthesis that should allow restoration of the
      essential functions of the larynx after a laryngectomy in cancer treatment.

PMID- 14655019
TI  - Only cerebral capillary amyloid angiopathy correlates with Alzheimer pathology--a
      pilot study.
AB  - Data on the relationship between cerebral amyloid angiopathy (CAA) ("congophilic
      angiopathy") and Alzheimer's disease (AD) pathology are conflicting. In the
      present study, CAA and capillary CAA (CapCAA) ("dyshoric angiopathy") were
      examined in the frontal cortex of 100 human brains obtained at autopsy from both
      male and female, demented and non-demented patients (mean age +/- SD 84.3+/-9.3
      years); 50 brains with high (mean 5.0) and 50 with low (mean 2.4) Braak stages.
      CAA was assessed according to the method of Olichney et al. [25]; CapCAA was
      grouped into four grades by counting the affected capillaries in 10 high power
      fields. General CAA was present in 61% (87.5% demented, 55.6% non-demented; 70%
      with high and 52% low Braak stages). CAA did not correlate with either clinical
      diagnosis of dementia or high-grade AD pathology; CapCAA showed a low correlation
      with dementia and a medium positive correlation with high Braak stages. The
      severity of both lesions did not correlate with clinical dementia; whereas that
      of CAA showed low correlation with CERAD, Braak, and NIA-Reagan-Institute
      criteria, the severity of CapCAA correlated significantly with all three AD
      criteria. The presence and severity of CAA and CapCAA showed only low
      correlation, suggesting a different pathogenesis of these types of lesion. Since
      CapCAA represents insoluble amyloid peptide (Abeta) deposits in and around
      capillaries, its correlation with neuritic AD pathology supports the concept of
      neuronal origin of Abeta via drainage from interstitial fluid from the central
      nervous system to capillary walls. Studies to answer the question whether CapCAA
      represents an epiphenomenon or an indicator of a pathogenic association between
      tau cytopathology and Abeta deposition in capillaries are in progress.

PMID- 14655020
TI  - Auditory-evoked evasive manoeuvres in free-flying locusts and moths.
AB  - We presented free-flying locusts (Locusta migratoria L.) with sounds that varied
      in temporal structure and carrier frequency as they flew toward a light source in
      a flight room under controlled temperature and light conditions. Previous studies
      have shown tethered locusts react more often to trains of 30-kHz pulses than to
      pulse trains below 10 kHz. Further, this acoustic startle response has been
      suggested to function in bat-avoidance. We expected free-flying locusts to
      respond similarly; however, we found locusts responded to all sounds we
      presented, not just high-frequency, "bat-like" sounds. Response rates of turns,
      loops, and dives varied from 6% to 26% but were statistically independent of
      carrier frequency and/or pulse structure. Free-flying moths and tethered locusts
      were tested using a subset of our acoustic stimuli under the same temperature and
      light conditions as the free-flying locusts. Moth responses were carrier
      frequency dependent as were responses of tethered locusts positioned along the
      flight path observed in our free-flight trials. All responses were unaffected by
      a 90% reduction in room light. We conclude that locusts possess an acoustic
      startle response evocable in free flight, however, free-flying locusts do not
      show the same discrimination observed in tethered locusts under similar
      conditions.

PMID- 14655021
TI  - Juvenile ankylosing spondylitis--is it the same disease as adult ankylosing
      spondylitis?
AB  - OBJECTIVES: Juvenile and adult forms of ankylosing spondylitis (AS) have been
      shown to have different clinical presentation and outcome in Caucasians. We did
      this retrospective analysis to see if similar differences exist in the Indian
      population. PATIENTS AND METHODS: Case records of 210 Indian patients diagnosed
      with AS according to modified New York criteria were reviewed. Data were
      collected regarding age of onset, clinical features, drug treatment, and outcome
      at last follow-up. Patients with onset before 17 years of age were classified as
      having juvenile AS (JAS) and the rest with adult AS (AAS). RESULTS: There were
      150 patients with AAS and 60 with JAS. The latter had higher male preponderance,
      more frequent onset with peripheral arthritis, and greater involvement of hip and
      knee joints. Valvular dysfunction was seen only in patients with JAS. CONCLUSION:
      In this group of subjects, juvenile AS had onset more often with oligoarthritis
      and enthesitis than with spinal disease. Hip and knee joint involvement was more
      common in JAS than AAS.

PMID- 14655023
TI  - Autoimmune disorders: a concept of treatment based on mechanisms of disease.

PMID- 14655024
TI  - Insulin-induced enhancement of antitumoral response to methotrexate in breast
      cancer patients.
AB  - PURPOSE: It has been reported that insulin increases the cytotoxic effect in
      vitro of methotrexate by as much as 10,000-fold. The purpose of this study was to
      explore the clinical value of insulin as a potentiator of methotrexate. PATIENTS
      AND METHODS: Included in this prospective, randomized clinical trial were 30
      women with metastatic breast cancer resistant to fluorouracil + Adriamycin +
      cyclophosphamide and also resistant to hormone therapy with measurable lesions.
      Three groups each of ten patients received two 21-day courses of the following
      treatments: insulin + methotrexate, methotrexate, and insulin, respectively. In
      each patient, the size of the target tumor was measured before and after
      treatment according to the Response Evaluation Criteria In Solid Tumors. The
      changes in the size of the target tumor in the three groups were compared
      statistically. RESULTS: Under the trial conditions, the methotrexate-treated
      group and the insulin-treated group responded most frequently with progressive
      disease. The group treated with insulin + methotrexate responded most frequently
      with stable disease. The median increase in tumor size was significantly lower
      with insulin + methotrexate than with each drug used separately. DISCUSSION: Our
      results confirmed in vivo the results of previous in vitro studies showing
      clinical evidence that insulin potentiates methotrexate under conditions where
      insulin alone does not promote an increase in tumor growth. Therefore, the
      chemotherapy antitumoral activity must have been enhanced by the biochemical
      events elicited in tumor cells by insulin. CONCLUSIONS: In multidrug-resistant
      metastatic breast cancer, methotrexate + insulin produced a significant
      antitumoral response that was not seen with either methotrexate or insulin used
      separately.

PMID- 14655025
TI  - Proliferative myositis in a patient with AIDS.
AB  - We report a case of proliferative myositis in the right biceps of a 56-year-old
      man with acquired immune deficiency syndrome (AIDS). Imaging methods included
      sonography, computed tomography and magnetic resonance imaging. The diagnosis was
      made by a core-cut biopsy and fine needle aspiration biopsy with
      immunohistochemical analysis. The lesion disappeared after 2 months without
      treatment. It is particularly important to determine whether intramuscular masses
      arising in patients with AIDS are due to an infectious or malignant process.

PMID- 14655026
TI  - Non-conventional yeasts as producers of polyhydroxyalkanoates--genetic
      engineering of Arxula adeninivorans.
AB  - The non-conventional yeast Arxula adeninivorans was equipped with the genes phbA,
      phbB and phbC of the polyhydroxyalkanoate (PHA) biosynthetic pathway of Ralstonia
      eutropha, which encode beta-ketothiolase, NADPH-linked acetoacetyl-CoA reductase
      and PHA synthase, respectively. Arxula strains transformed solely with the PHA
      synthase gene (phbC) were able to produce PHA. However, the maximum content of
      the polymer detected in these strains was just 0.003% poly-3-hydroxybutyrate
      (PHB) and 0.112% poly-3-hydroxyvalerate (PHV). The expression of all three genes
      (phbA, phbB, phbC) resulted in small increases in the PHA content of the
      transgenic Arxula cells. However, under controlled cultivation conditions with
      minimal medium and ethanol as the carbon source, the recombinant yeast was able
      to accumulate up to 2.2% PHV and 0.019% PHB. Possible reasons for these
      differences are discussed.

PMID- 14655027
TI  - Identification of the tautomeric form of formycin A in its complex with
      Escherichia coli purine nucleoside phosphorylase based on the effect of enzyme
      ligand binding on fluorescence and phosphorescence.
AB  - Fluorescence and phosphorescence emission spectroscopy were employed to study the
      interaction of Escherichia coli purine nucleoside phosphorylase (PNP) with its
      specific inhibitor, formycin A (FA), a close structural analogue of adenosine
      (natural substrate), in the absence and presence of phosphate (P(i), substrate).
      Formation of enzyme-FA complexes led to marked quenching of enzyme tyrosine
      intrinsic fluorescence and phosphorescence, with concomitant increases in
      fluorescence and phosphorescence of FA. Fluorescence resonance energy transfer
      from the protein Tyr160 residue to the FA base moiety was identified as a major
      mechanism of protein fluorescence quenching, increased by addition of P(i). The
      effects of enzyme-FA interactions on the nucleoside excitation and emission
      spectra for fluorescence and phosphorescence revealed shifts in the tautomeric
      equilibrium of the bound FA, i.e. from the N(1)-H tautomer (predominant in
      solution) to the N(2)-H form, enhanced by the presence of P(i). The latter was
      confirmed by enzyme-ligand dissociation constant ( K(d)) values of 5.9+/-0.4 and
      2.1+/-0.3 microM in the absence and presence of P(i), respectively. Addition of
      glycerol (80%, v/v) led to a lower enzyme affinity ( K(d) approximately 70
      microM), without changes in binding stoichiometry. Enzyme-FA complex formation
      led to a higher increase of the fluorescence than the phosphorescence band of the
      ligand, consistent with the fact that the N(2)-H tautomer is characterized by a
      weaker phosphorescence than the N(1)-H tautomeric form. These results show, for
      the first time, the application of phosphorescence spectroscopy to the
      identification of the tautomeric form of the inhibitor bound by the enzyme.

PMID- 14655028
TI  - Structure-based calculation of multi-donor multi-acceptor fluorescence resonance
      energy transfer in the 4x6-mer tarantula hemocyanin.
AB  - Hemocyanins are oxygen carriers of arthropods and molluscs. The oxygen is bound
      between two copper ions, forming a Cu(II)-O(2)(2-)-Cu(II) complex. The oxygenated
      active sites create two spectroscopic signals indicating the oxygen load of the
      hemocyanins: first, an absorption band at 340 nm which is due to a ligand-to
      metal charge transfer complex, and second, a strong quenching of the intrinsic
      tryptophan fluorescence, the cause of which has not been definitively identified.
      We showed for the 4x6-mer hemocyanin of the tarantula Eurypelma californicum that
      the fluorescence quenching of oxygenated hemocyanin is caused exclusively by
      fluorescence resonance energy transfer (FRET). The tarantula hemocyanin consists
      of 24 subunits containing 148 tryptophans acting as donors and 24 active sites as
      acceptors. The donor-acceptor distances are determined on the basis of a closely
      related crystal structure of the horseshoe crab Limulus polyphemus hemocyanin
      subunit II (68-79% homology). Calculation of the expected fluorescence quenching
      and the measured transfer efficiency coincided extraordinary well, so that the
      fluorescence quenching of oxygenated tarantula hemocyanin can be completely
      explained by Forster transfer. This results explain for the first time, on a
      molecular basis, why fluorescence quantum yield can be used as an intrinsic
      signal for oxygen load of at least one arthropod hemocyanin, in particular that
      from the tarantula.

PMID- 14655029
TI  - A microbubble agent improves the therapeutic efficiency of high intensity focused
      ultrasound: a rabbit kidney study.
AB  - Eighty kidneys (40 left and 40 right kidneys) of New Zealand rabbits were ablated
      using high intensity focused ultrasound (HIFU), (14,300 W/cm(2), 1.0 MHz).
      Kidneys were randomly divided into two groups. HIFU was performed in the manner
      of linear scan in both groups. Prior to HIFU, normal saline solution and
      isovolumetric microbubble agent were administrated intravenously in groups I and
      II, respectively. HIFU was finished in all left kidneys and in 26/40 right ones.
      The therapeutic efficiency was reflected using necrosis rate (cubic centimeters
      per second), which was the tissue volume of coagulative necrosis per 1 s HIFU
      exposure. In both groups, predetermined volumes were damaged without harming
      overlying tissues. Necrosis rates were increased in group II both in left
      (0.0089+/-0.0107 vs. 0.0493+/-0.0777, P=0.0323) and in right (0.0039+/-0.0055 vs.
      0.0162+/-0.0168, P=0.0248) kidneys. Pathological examinations confirmed that
      there were no intact tissue focuses within exposed regions in either group. These
      findings suggested that the microbubble agent improved the therapeutic efficiency
      of HIFU. Hemorrhage and hyperemia were also detected on the margin of the ablated
      tissues (both in cortex and medulla) in both groups.

PMID- 14655030
TI  - Percutaneous transluminal angioplasty of proximal vertebral artery stenosis: long
      term clinical follow-up of 16 consecutive patients.
AB  - We report long-term (average 30 months) clinical and radiological follow-up of 16
      consecutive patients with uni- or bilateral proximal vertebral artery stenosis
      who underwent percutaneous transluminal angioplasty (PTA), without stenting,
      between 1995 and 1998. Assessment was performed by an independent neurologist.
      All patients but one remained asymptomatic during follow-up; moderate restenosis
      was observed in four. PTA of the proximal vertebral artery is safe but in the
      absence of knowledge of the natural history of atherosclerotic vertebral artery
      stenosis, whether it is beneficial or not remains unproven. The decision as to
      whether to perform this procedure is individual.

PMID- 14655032
TI  - Asymptomatic middle cerebral artery stenosis diagnosed by magnetic resonance
      angiography.
AB  - We reviewed 1440 MRA studies to identify patients with middle cerebral artery
      stenosis (MCAS). We identified 99 cases, and after reviewing the clinical
      records, classified 28 as asymptomatic MCAS (AMCAS), a prevalence of 2%.
      Suspected stroke was the most frequent indication for MRA. Follow-up was
      available for 21, mean 46.7 months (range 2.4-75.6 months). One stroke occurred
      in the AMCAS territory (5%), other strokes in five patients (24%). There were
      five deaths in patients with MCAS; age > 69 (P = 0.045) was the only associated
      risk factor. This study suggests that patients in whom MRA is performed and shows
      AMCAS may be at increased risk of strokes in any vascular distribution or of
      death.

PMID- 14655033
TI  - Targeted compartmental embolization of cavernous sinus dural arteriovenous
      fistulae using transfemoral medial and lateral facial vein approaches.
AB  - There are multiple transvenous approaches for treatment of cavernous dural
      arteriovenous fistulae (DAVF). The choice of a specific route depends on the
      compartment of the cavernous sinus involved in the fistula and its venous
      drainage. We used two different facial vein approaches to treat patients with
      cavernous DAVF draining directly into the anterior compartment of the cavernous
      sinus and thence to the superior ophthalmic vein. Other transvenous routes to the
      sinus were not apparent. Embolization was targeted to the involved compartment
      with preservation of those not embolized. No major post-procedure ophthalmic
      venous engorgement occurred. We believe that ideal treatment of cavernous DAVF is
      targeted transvenous coil deposition, which necessitates detailed knowledge of
      the anatomy of the facial veins and cavernous sinus compartments.

PMID- 14655034
TI  - MRI in acute subarachnoid haemorrhage; findings with a standardised stroke
      protocol.
AB  - There is doubt as to whether acute haemorrhage is visible on MRI. We carried out
      MRI within 6 h of symptom onset on five patients with minor (low Hunt and Hess
      grades 1 or 2) subarachnoid haemorrhage (SAH) diagnosed by CT to search for any
      specific pattern. We used our standard stroke MRI protocol, including multiecho
      proton density (PD)- and T2-weighted images, echoplanar (EPI) diffusion- (DWI)
      and perfusion- (PWI) weighted imaging, and MRA. In all cases SAH was clearly
      visible on PD-weighted images with a short TE. In four patients it caused a low
      signal rim on the T2*-weighted source images of PWI, and DWI revealed high signal
      in SAH. In the fifth patient SAH was perimesencephalic; susceptibility effects
      from the skull base made it impossible to detect SAH on EPI DWI and T2*-weighted
      images. Perfusion maps were normal in all cases. MRA and conventional angiography
      revealed an aneurysm in only one patient. Stroke MRI within 6 h of SAH thus shows
      a characteristic pattern.

PMID- 14655035
TI  - Social communication in siamangs (Symphalangus syndactylus): use of gestures and
      facial expressions.
AB  - The current study represents the first systematic investigation of the social
      communication of captive siamangs (Symphalangus syndactylus). The focus was on
      intentional signals, including tactile and visual gestures, as well as facial
      expressions and actions. Fourteen individuals from different groups were observed
      and the signals used by individuals were recorded. Thirty-one different signals,
      consisting of 12 tactile gestures, 8 visual gestures, 7 actions, and 4 facial
      expressions, were observed, with tactile gestures and facial expressions
      appearing most frequently. The range of the signal repertoire increased steadily
      until the age of six, but declined afterwards in adults. The proportions of the
      different signal categories used within communicative interactions, in particular
      actions and facial expressions, also varied depending on age. Group differences
      could be traced back mainly to social factors or housing conditions. Differences
      in the repertoire of males and females were most obvious in the sexual context.
      Overall, most signals were used flexibly, with the majority performed in three or
      more social contexts and almost one-third of signals used in combination with
      other signals. Siamangs also adjusted their signals appropriately for the
      recipient, for example, using visual signals most often when the recipient was
      already attending (audience effects). These observations are discussed in the
      context of siamang ecology, social structure, and cognition.

PMID- 14655036
TI  - Sepsis with bullous necrotizing skin lesions due to vibrio vulnificus acquired
      through recreational activities in the Baltic Sea.
AB  - This report describes the case of a 59-year-old woman with a history of non
      Hodgkin's lymphoma who developed bacteremia with Vibrio vulnificus. The patient
      had been swimming in the unusually warm Baltic Sea in the summer of 2002. She
      presented with symptoms of septicemia and severe bullous necrotizing skin lesions
      of the extremities. Blood culture revealed Vibrio vulnificus as the pathogenic
      organism. Under treatment with cefotaxime and gentamicin, she recovered slowly
      without further complications. Vibrio vulnificus is a marine bacterium that is
      present in aquatic ecosystems worldwide, especially when water temperatures
      exceed 20 degrees C. Infections with Vibrio vulnificus are uncommon in Europe,
      and most cases are reported from subtropical or tropical regions.

PMID- 14655037
TI  - Comparison of the accuracy of semiempirical and some DFT methods for predicting
      heats of formation.
AB  - A comparison is made of the relative accuracy of some NDDO semiempirical methods
      and the DFT functionals LYP and PW91 using both double and triple zeta basis
      sets. The comparison is between the calculated heat of formation and that
      reported in the NIST database.

PMID- 14655038
TI  - Determination of DNA guanine sites forming photo-adducts with Ru(II)-labeled
      oligonucleotides; DNA polymerase inhibition by the resulting photo-crosslinking.
AB  - The influence of the distance between the anchoring site of the tethered
      [Ru(TAP)(2)dip](2+) complex (TAP=1,4,5,8-tetraazaphenanthrene; dip=4,7-diphenyl
      1,10-phenanthroline) on a probe sequence and the guanines of the complementary
      target strand was studied by (1) the luminescence quenching of the complex (by
      electron transfer) and (2) the oligodeoxyribonucleotide adduct (ODN adduct)
      formation which results in photo-crosslinking of the two strands. Moving the
      guanine moieties away from the complex induces an important decrease of the
      efficiency of both processes, but clearly affects the ODN adduct formation more
      specifically than the quenching process. From these results, we determined the
      positions of the guanine bases in the duplex ODN that are able to form a photo
      adduct with the tethered complex. We also examined the possible competition
      between a long-range hole migration in the duplex ODN and the formation of a
      photo-adduct by using a sequence labeled with the complex at the 5'-phosphate
      end. Such a hole migration appears to be inefficient as compared to the ODN
      adduct formation. Finally, we studied the influence of the photo-crosslinking on
      the function of two different DNA polymerases. A 17-mer Ru(II)-labeled ODN was
      hybridized to its complementary sequence located on the 5'-side of a 40-mer
      matrix. After illumination, the elongation of a 13-mer DNA primer hybridized to
      the 3'-extremity of the same matrix was stopped at a position corresponding to
      the formation of the ODN adduct.

PMID- 14655039
TI  - Growth and survival of seedlings of native plants in an impoverished and highly
      disturbed soil following inoculation with arbuscular mycorrhizal fungi.
AB  - We investigated whether arbuscular mycorrhizas influenced growth and survival of
      seedlings in an extremely impoverished and highly disturbed soil. Seedlings of
      four plants species native to the site were either inoculated with native
      sporocarpic arbuscular mycorrhizal (AM) fungi or fertilised prior to
      transplanting, and followed over 86 weeks at the site. One treatment was also
      irrigated with N-rich leachate from the site. In a laboratory experiment,
      seedlings were fertilised with excess P for 6 weeks, and location of the P store
      determined. Growth and survival of AM and fertilised seedlings were similar at
      the site. Inoculated mycorrhizal fungi and roots appeared to extend into the
      surrounding soil together. P concentration in leaves of all plants was extremely
      low. Irrigation with leachate increased growth of seedlings. In the laboratory
      experiment, significantly more P was stored in roots than shoots. We suggest that
      successful revegetation of extremely disturbed and impoverished sites requires
      selection of mycorrhizal fungi and plants to suit the edaphic conditions and
      methods of out-planting.

PMID- 14655040
TI  - Mycorrhiza of plants in different vegetation types in tropical ecosystems of
      Xishuangbanna, southwest China.
AB  - We examined plants growing in four tropical vegetation types (primary forest,
      secondary forest, limestone forest and a slash and burn field) in Xishuangbanna,
      southwest China for mycorrhizal associations. Of the 103 plant species examined
      (belonging to 47 families), 81 had arbuscular mycorrhizal (AM) associations,
      while three species possessed orchid mycorrhiza. AM colonization levels ranged
      between 6% and 91% and spore numbers ranged between 1.36 spores and 25.71 spores
      per 10 g soil. Mean AM colonization level was higher in primary and secondary
      forest species than in plant species from limestone forests and a slash and burn
      field. In contrast, mean AM fungal spore numbers of the primary and limestone
      forest were lower than in the secondary forest or the slash and burn field. AM
      fungal spores belonging to Glomus and Acaulospora were the most frequent in soils
      of Xishuangbanna. AM fungal colonization and spore numbers were significantly
      correlated to each other and were significantly influenced by vegetation type.

PMID- 14655041
TI  - Multicenter, randomized trial of ramosetron plus dexamethasone versus ramosetron
      alone in controlling cisplatin-induced emesis.
AB  - GOALS: To establish whether the combination of a corticosteroid (dexamethasone)
      and the newer serotonin-3 (5-HT(3)) receptor antagonist ramosetron is superior to
      ramosetron alone in controlling cisplatin-induced emesis. PATIENTS AND METHODS: A
      total of 283 patients aged 18-75 years with confirmed malignant disease who were
      scheduled to receive cisplatin > or =50 mg/m(2) with or without other
      antineoplastic agents were randomized to intravenous treatment with either
      ramosetron 300 microg plus dexamethasone 20 mg ( n=149) or ramosetron 300 microg
      alone ( n=134) given 30 min prior to cisplatin infusion. If vomiting occurred in
      the following 24 h, patients in both groups received an intravenous rescue dose
      of ramosetron 300 microg. Subsequently, on days 2 and 3, treatment was continued
      orally with either ramosetron 100 microg once daily plus dexamethasone 8 mg twice
      daily, or ramosetron 100 microg once daily. MAIN RESULTS: During the first 24 h
      after cisplatin infusion, significantly more patients receiving combination
      therapy had a complete response (no nausea or vomiting or requirement for rescue
      therapy) than those receiving ramosetron alone (68% vs 54%, respectively;
      P=0.034), and significantly fewer patients needed a rescue dose of ramosetron
      (22% vs 34%, respectively; P=0.032). In addition, the percentages of patients
      with no nausea and no vomiting were significantly greater in the ramosetron plus
      dexamethasone group than in the ramosetron-alone group at both 24 h and 72 h
      after cisplatin administration. CONCLUSIONS: The antiemetic efficacy of
      ramosetron in cancer patients receiving highly emetogenic cisplatin chemotherapy
      is significantly enhanced by its use in combination with dexamethasone.

PMID- 14655042
TI  - Symptom control and palliative care content of abstracts presented at the
      Canadian Association of Radiation Oncologists annual meetings.
AB  - GOALS: Half of all patients referred for radiotherapy are treated with palliative
      intent. Recent emphasis has been placed on the importance of symptom control and
      palliative care (SCPC) in the radiation oncology community. The purpose of this
      study was to determine the number of abstracts relating to SCPC presented at the
      annual Canadian Association of Radiation Oncologists (CARO) meetings, and whether
      this number has increased over time. METHODS: SCPC abstracts presented at CARO
      from 1992 through 2002 were counted. Abstracts were included if they described a
      patient population with advanced or metastatic cancer treated with palliative
      intent. Abstracts were then categorized as reporting treatment outcomes, health
      services research, descriptive studies or literature reviews. Radiation treatment
      sites were recorded. MAIN RESULTS: An average of 6.7% (60/892; range 0-16.2%) of
      all abstracts presented at CARO from 1992 through 2002 pertained to SCPC. There
      was a significant increase in the proportion of SCPC abstracts accepted over time
      ( P=0.0012). Descriptive studies accounted for 46.7%, treatment outcomes 31.7%,
      health services research 13.3%, and literature reviews 8.3% of the SCPC
      abstracts. Bone metastases (48.3%), primary lung tumors (11.7%), and brain
      metastases (10.0%) were the most common treatment sites. Of all the SCPC
      abstracts, 45% came from dedicated palliative radiotherapy clinics. CONCLUSIONS:
      SCPC research is poorly represented at the annual CARO conferences. Research in
      this field should be promoted as the palliative patient population represents a
      large component of radiotherapy clinical practice. The recent emergence of
      dedicated palliative radiotherapy clinics should continue to increase palliative
      radiotherapy research.

PMID- 14655043
TI  - Practitioners' sources of clinical information on complementary and alternative
      medicine in oncology.
AB  - GOALS OF WORK: The use of complementary and alternative medicine (CAM) amongst
      oncology patients is widespread. There is little data regarding the sources of
      clinical information on CAM that oncology practitioners utilise. The aim of this
      study was to investigate the sources of clinical information on CAM utilised by
      Australian oncology practitioners. METHODS: A structured self-administered
      questionnaire was sent to Australian oncology practitioners, defined as
      oncologists, oncology pharmacists and pharmacists at drug information centres
      (DICs). Key information was sought on their level of satisfaction with the
      accessibility, reliability and usefulness of this information and the frequency
      of, and initiating factors for, seeking this information. MAIN RESULTS: A
      substantial proportion of oncologists (57.1%) reported having never sought
      information on CAM, compared to 27.3% of oncology pharmacists, and 18.8% of DIC
      pharmacists. Oncologists most commonly reported seeking information on CAM one to
      three times per year compared to four to ten times per year for oncology
      pharmacists. Databases were the most common information source used by
      oncologists (48.1%) and oncology pharmacists (91.7%) and the second most common
      information source used by DICs (92.3%). There was wide variation in the source
      of clinical information on CAM used by the three different professional groups.
      CONCLUSION: . Oncology practitioners often seek information on CAM; however the
      frequency, nature and sources of information utilised varied widely. The
      usefulness and reliability of the sources utilised were inconsistent.

PMID- 14655044
TI  - Persistent maternal identity effects on life history traits in Daphnia.
AB  - The aim of the present study was to examine the magnitude and persistence of
      maternal effects in Daphnia, in particular maternal identity effects. I studied
      life history traits of a single clone of Daphnia galeata born to 40 different
      mothers belonging to three age groups. Maternal identity had large effects on
      offspring traits, that is, identically treated clonal females differed
      substantially in respect to the traits of their offspring, including size at
      birth, age at maturity, and number of second generation offspring. The effects of
      maternal identity on these traits were largely independent of maternally induced
      differences in offspring size, indicating that maternal effects were mediated
      through offspring quality. Maternal age also affected offspring traits: older
      mothers gave birth to larger offspring which matured earlier, were larger and
      more fecund, and survived better until maturity. Individuals which were larger at
      birth also had a better chance of survival. Contrary to expectation, I found
      little evidence that maternal identity or maternal age had any influence on their
      offsprings' response to fish kairomones.

PMID- 14655045
TI  - The subsets of keratinocytes responsible for covering open wounds in neonatal rat
      skin.
AB  - Full-thickness excisional wounds were made on the dorsal skin of 1-day-old rats
      to elucidate from where the cells move into the defect and what kinds of cells
      they are. Immunohistochemical analyses of the wound sites revealed that the
      following two subsets of keratinocytes were the major contributors to
      reepithelialization: first, the cells at the forefront of the migrating
      epithelium, termed "leading edge cells," which expressed K14 keratin, known as
      basal cell-specific keratin, but not K6 or K10 keratins, so that they had
      probably moved from the basal cell layer; and, second, the cells tentatively
      termed "immature spinous cells," which expressed K14 and K6 but not K10, and
      formed an "ingrowth region" following the leading edge cells. These two kinds of
      cells moved to the open wound area, as a multilayered cell sheet. Fluorescent
      phalloidin staining experiments indicated that actin filaments became
      concentrated in the leading edge cells within 6 h postwounding (PW), whereas weak
      signals of actin filaments were detected in the immature spinous cells. Taken
      together, the present findings support the view that wound covering in neonatal
      rat skin is accomplished by a movement en masse of keratinocytes from the bottom
      half of the surrounding epidermis.

PMID- 14655047
TI  - Two different heat shock transcription factors regulate immediate early
      expression of stress genes in Arabidopsis.
AB  - In order to assess the specific functional roles of different plant heat shock
      transcription factors (HSFs) we have isolated T-DNA insertion mutants in the
      AtHsf1 and AtHsf3 genes of Arabidopsis thaliana. Complete and selective loss of
      the promoter binding activities of AtHSF1 or AtHSF3, verified by
      immunoprecipitation assays, had no obvious effects on the heat shock (HS)
      response in the individual mutant lines. Only hsf1(-) /hsf3(-)double mutants were
      significantly impaired in HS gene expression. In these plants the inability to
      form high-molecular-weight HSE-binding complexes correlates with a dramatic
      change in the kinetics of mRNA accumulation from all HSF target genes tested,
      including members of the Hsp100, Hsp90, Hsp70 and small Hsp families, and genes
      for two heat-inducible class B-HSFs. After prolonged HS, the amounts of most heat
      shock mRNAs expressed, except transcripts of Hsp18.2, reached approximately the
      same levels as in wild type plants. Our data indicate that AtHSF1 and AtHSF3 are
      key regulators of the immediate stress-induced activation of HS gene
      transcription, and consequently determine the kinetics of the negative feed back
      loop that is responsible for the transience of HS gene expression in wild type.

PMID- 14655048
TI  - Recombinant expression of the larval excretory-secretory antigen TES-120 of
      Toxocara canis in the methylotrophic yeast Pichia pastoris.
AB  - A gene encoding the larval excretory-secretory antigen TES-120 of the dog ascarid
      worm Toxocara canis was cloned into the methylotrophic yeast Pichia pastoris.
      Specificity of the recombinant TES-120 antigen produced by the yeast was
      investigated. Forty-five human serum samples from patients infected with
      different()parasitic organisms, including 8 cases of toxocariasis, were tested
      against the recombinant antigen in immunoblot assays. Results from the assays
      showed that the recombinant TES-120 antigen reacted with sera from toxocariasis
      patients only. This highly specific recombinant TES-120 antigen can potentially
      be used for the development of an inexpensive serodiagnostic assay for human
      toxocariasis.

PMID- 14655046
TI  - Two-hybrid search for proteins that interact with Sad1 and Kms1, two membrane
      bound components of the spindle pole body in fission yeast.
AB  - In interphase cells of fission yeast, the spindle pole body (SPB) is thought to
      be connected with chromosomal centromeres by an as yet unknown mechanism that
      spans the nuclear membrane. To elucidate this mechanism, we performed two-hybrid
      screens for proteins that interact with Kms1 and Sad1, which are constitutive
      membrane-bound components of the SPB that interact with each other. Seven and 26
      genes were identified whose products potentially interact with Kms1 and Sad1,
      respectively. With the exception of Dlc1 (a homolog of the 14-kDa dynein light
      chain), all of the Kms1 interactors also interacted with Sad1. Among the genes
      identified were the previously known genes rhp9+ / crb2+, cut6+, ags1+ / mok1+,
      gst3+, kms2+, and sid4+. The products of kms2+ and sid4+ localize to the SPB. The
      novel genes were characterized by constructing disruption mutations and by
      localization of the gene products. Two of them, putative homologues of budding
      yeast UFE1 (which encodes a t-SNARE) and SFH1 (an essential component of a
      chromatin-remodeling complex), were essential for viability. Two further genes,
      which were only conditionally essential, genetically interact with sad1+. One of
      these was named sif1+ (for Sad1-interacting factor) and is required for proper
      septum formation at high temperature. Cells in which this gene was overexpressed
      displayed a wee -like phenotype. The product of the other gene, apm1+, is very
      similar to the medium chain of an adaptor protein complex in clathrin-coated
      vesicles. Apm1 appears to be required for SPB separation and spindle formation,
      and tended to accumulate at the SPB when it was overproduced. It was functionally
      distinct from its homologues Apm2 and Apm4. Other novel genes identified in this
      study included one for a nucleoporin and genes encoding novel membrane-bound
      proteins that were genetically related to Sad1. We found that none of the newly
      identified genes tested were necessary for centromere/telomere clustering.

PMID- 14655049
TI  - In vivo establishment and characterization of a paclitaxel-resistant human
      ovarian cancer cell line showing enhanced growth properties and drug-resistance
      only in vivo.
AB  - PURPOSE: In order to establish a more faithful model of clinically recurrent
      ovarian cancer after paclitaxel-based chemotherapy, a paclitaxel-resistant human
      ovarian cancer cell line was established in vivo, and its biological profiles
      were compared with the conventional in vitro established drug-resistant cell
      line. METHODS: An in vivo paclitaxel-resistant subline (OM1/Tvivo) was
      established from the parental human ovarian cancer cell line (OVMG1) by repeated
      paclitaxel administration into tumor-bearing mice. As a control, the in vivo drug
      sensitive subline (OM1/Cvivo) was made in the same manner, without paclitaxel. An
      in vitro paclitaxel-resistant subline (OM1/Tvitro) was established by exposure to
      stepwise increased concentrations of the drug in a cell culture medium.
      Chromosomal analysis, evaluation of growth, invasiveness and metastasis, in vivo
      and in vitro drug sensitivity, and a pharmacokinetic study were performed.
      RESULTS: Both in vivo sublines confirmed their human origin by G-band chromosomal
      analysis and showed a similar cell growth rate in cell culture. As for in vivo
      tumor growth, OM1/Tvivo showed enhanced tumor growth property compared with
      OM1/Cvivo, while OM1/Tvitro lost tumorigenicity. Both OM1/Tvivo and OM1/Cvivo
      sublines as well as their parental OVMG1 could not form either invasive or
      metastatic lesions. Compared with the OM1/Cvivo subline, the OM1/Tvivo tumor
      showed stable drug-resistance and lower drug distribution after paclitaxel
      administration into mice, whereas cultured OM1/Tvivo cells lost both completely.
      On the other hand, an unreasonably higher level of drug-resistance and lower drug
      concentration was detected in vitro only in OM1/Tvitro cells after exposure to
      the drug in a culture medium. CONCLUSIONS: These results suggest that the in vivo
      established paclitaxel-resistant cell line, rather than the conventional in vitro
      established cell line, is a suitable and faithful model for clinically recurrent
      tumors showing transformed aggressiveness. The in vivo specific drug-resistant
      mechanism should involve an interaction between the tumor and host stromal tissue
      rather than only changes in cellular drug sensitivity. The present study is
      probably the first report of an in vivo established paclitaxel-resistant human
      ovarian cancer cell line, and the elucidation of such an in vivo drug-resistance
      mechanism may be clinically important in preventing or overcoming acquired drug
      resistant ovarian cancers recurring after paclitaxel-based chemotherapy.

PMID- 14655051
TI  - Statistics in medicine.

PMID- 14655050
TI  - Down-regulation of a gastric transcription factor, Sox2, and ectopic expression
      of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during
      progression from gastric/intestinal-mixed to complete intestinal metaplasia.
AB  - PURPOSE: The molecular mechanisms underlying the development of intestinal
      metaplasia (IM) of the human stomach have yet to be clarified in detail. Besides
      ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, little
      information is available regarding other regulatory factors. Hence, we here
      analyzed Sox2, a human homolog of a chicken gastric transcription factor, with
      reference to our new classification for gastric/intestinal (GI)-mixed type IM.
      METHODS: Twenty specimens of surgically resected antral mucosa were subjected to
      a gland isolation technique. Isolated glands were classified into gastric (G), GI
      mixed, and solely intestinal (I) types according to Alcian blue and paradoxical
      concanavalin A staining and were quantified for mRNA levels of gastrointestinal
      markers. RESULTS: MUC5AC and MUC6 transcripts decreased with the progression of
      IM, while MUC2 and villin-1 were inversely correlated. Sox2 showed a gradual
      decrease from G, through GI, to the I type (G vs GI and GI vs I, P<0.01 and
      P<0.005, respectively). On the other hand, Cdx1 (G vs GI and GI vs I, P<0.0001
      and P=0.337, respectively) and Cdx2 (G vs GI and GI vs I, P<0.0001 and P<0.05,
      respectively) appeared in IM. Immunohistochemical study confirmed decreased
      expression of Sox2 and ectopic emergence of Cdx2 protein in IM glands.
      CONCLUSION: Down-regulation of Sox2, besides ectopic expression of Cdx genes, may
      be important factors for the development of IM.

PMID- 14655052
TI  - Statistics in medical research.
AB  - The role of statistics in medical research starts at the planning stage of a
      clinical trial or laboratory experiment to establish the design and size of an
      experiment that will ensure a good prospect of detecting effects of clinical or
      scientific interest. Statistics is again used during the analysis of data (sample
      data) to make inferences valid in a wider population. In simple situations
      computation of simple quantities such as P-values, confidence intervals, standard
      deviations, standard errors or application of some standard parametric or
      nonparametric tests may suffice. Despite their wide use even these simple notions
      are sometimes misunderstood or misinterpreted by research workers in other
      disciplines who have only a limited knowledge of statistics. More sophisticated
      research projects often need advanced statistical methods including the
      formulation and testing of mathematical models to make relevant inferences from
      observed data. Such advanced methods should only be applied with a clear
      understanding both of their purposes and the implication of any conclusions based
      upon their use. Close collaboration between statisticians, whether professionals
      in that field or medical research workers with a sound statistical background,
      and other members of a research team is needed to ensure a seamless integration
      of the statistical elements into the reporting and discussion of research
      outcomes. Some suggestions are made as to how that collaboration is best
      achieved.

PMID- 14655053
TI  - Quality of diabetes care: problem of patient or doctor adherence?
AB  - Current guidelines for treatment of type 2 diabetes mellitus include disease
      prevention and the control of blood pressure and lipids in addition to blood
      glucose management. However, physician compliance with treatment guidelines is
      relatively poor. In any given year, HbA1c and blood lipids are measured only in
      about half of patients and are below target in even less, while blood pressure is
      frequently measured but controlled in less than 50%. Some reasons for this
      unsatisfactory situation are providers' beliefs, frustration and lack of
      knowledge, patient barriers and the fact that the guidelines are not easy to
      access and implement. Patient non-adherence can be changed by improving
      education, perception, motivation and self-management. Strategies for improving
      disease management are discussed.

PMID- 14655054
TI  - The influence of gender and personality traits on the career planning of Swiss
      medical students.
AB  - BACKGROUND AND OBJECTIVES: Since the 1990s, as many women as men have been
      entering and graduating from medical schools in Western countries. Up to date,
      prospective studies of physicians' career paths are lacking. This paper presents
      the data of the first assessment of a longitudinal survey of a cohort of Swiss
      medical school graduates, evaluated with regard to how gender and personality
      traits contribute to their academic achievement and further career planning.
      METHODS: In 2001, 719 graduate students (52.9% females, 47.1% males) returned a
      postal questionnaire comprising sections on personality traits, career
      motivation, and career planning. RESULTS: Female graduates scored higher on
      traits such as helpfulness, relationship consciousness, empathy, family
      responsibility, and job security. Male students scored higher on traits such as
      independence, decisiveness, self-confidence, activity, income, and prestige.
      Women were further advanced in the writing of their thesis (p = 0.04), chose
      different topics (p <0.001), and had more often decided in which field they
      wished to specialise (p =.02). Women preferred fields with intensive patient
      contact (p <0.01), men tended to specialise more in instrumentally oriented and
      high-technology medicine (p <.001). The regression model revealed that, apart
      from gender (being female), instrumentality and extrinsic career motivation
      predict advanced academic achievement, whereas self-esteem and intrinsic career
      motivation influence the choice of speciality. CONCLUSIONS: The results indicate
      that women plan their career more purposefully than men, and that not only gender
      but also personality traits and career motivation play an important role in
      academic achievement and career planning.

PMID- 14655055
TI  - HLA-DRB1 association in Turkish psoriasis vulgaris patients.

PMID- 14655056
TI  - Aphthous colitis induced by non-steroidal antirheumatic drugs.

PMID- 14655057
TI  - Determination of serum hepatitis B virus DNA in chronic HBsAg carriers: clinical
      significance and correlation with serological markers.
AB  - BACKGROUND/AIMS: Hepatitis B virus infection is among the most devastating health
      problems in the world, including Turkey. In this cross-sectional study, we aimed
      to investigate the correlations between hepatitis B virus genomic load and
      various measures of the progression of chronic hepatitis B virus infection.
      METHODS: A total of 354 chronic HBsAg carriers [126 inactive HBsAg carriers, 50
      asymptomatic replicative carriers (immune tolerant patients), 90 chronic
      hepatitis B patients and 88 patients with liver cirrhosis] were enrolled into the
      study. Eligible patients included males and females, 14-62 years of age, with
      detectable serum HBsAg, HBeAg or anti-HBe in serum at the time of screening and
      for at least six months before study entry. Serum hepatitis B virus DNA was
      detected by liquid hybridization, and results under the level of 1 pg/ml were
      additionally confirmed by polymerase chain reaction. RESULTS: Of 354 patients,
      118 (33%) were HBeAg-positive and 236 (67%) HBeAg-negative. Of HBeAg-negative
      patients, 126 (53%) had normal alanine aminotransferase, 31 (13%) had elevated
      alanine aminotransferase (chronic hepatitis B) and 79 (33%) had evidence of
      cirrhosis; corresponding figures in the HBeAg-positive patients were 50 (42%), 59
      (50%) and 9 (8%). There is a significant correlation between transaminase values
      and histological liver damage, whereas no correlation was found between viral
      replication and liver damage. CONCLUSIONS: Hepatitis B virus DNA is an important
      and specific marker for ongoing hepatitis B virus related liver disease, but
      alanine aninotransferase was shown to be the best marker for liver inflammation
      and not hepatitis B virus viral load. Although these findings are not new, they
      are of some utility since they prevent unnecessary and cost-intensive viral load
      determinations in chronic HBsAg carriers.

PMID- 14655058
TI  - Experience with liver dialysis in acetaminophen induced fulminant hepatic
      failure: a preliminary report.
AB  - BACKGROUND/AIMS: Our aim was to assess the efficacy of the liver dialysis unit
      (LDU) in the treatment of patients with acetaminophen-induced fulminant hepatic
      failure. METHODS: Seventeen patients with acetaminophen-induced fulminant hepatic
      failure between January 1996 and December 2001 were retrospectively studied. A
      liver dialysis unit became available in our Unit in July 2000, and as of December
      2001, four of these 17 patients had undergone treatment with liver dialysis.
      RESULTS: Mean age was 29 years (range: 14-47) and 76% were women. Four of 17
      patients underwent a total of 12 (range: 1-4) LDU sessions. Ammonia level tended
      to be lower following the LDU and all four patients recovered without a need for
      orthotopic liver transplantation (OLT). Prior to July 2000, eight of 13 patients
      survived with supportive therapy, three expired and two underwent OLT. No major
      bleeding episodes were observed during the LDU course. A significant difference
      was found between the three cases who died and the cases that survived with
      respect to the grade of encephalopathy (p<0.001). There was significant
      difference in the admission serum creatinine among survivors (p<0.05).
      CONCLUSION: In conclusion, the Liver Dialysis Unit treatment appeared to benefit
      patients with acetaminophen-induced fulminant hepatic failure by reverse of the
      encephalopathy and spontaneous recovery of the damaged liver in selected
      patients.

PMID- 14655059
TI  - Expression of class I and II MHC receptors in Helicobacter pylori-positive
      patients with active gastritis and duodenal ulcer.
AB  - BACKGROUND/AIMS: Helicobacter pylori colonizes on the epithelial surface below
      the mucous membrane in the gastric antrum, causing chronic active gastritis and
      duodenal ulcer. However, we know little about the response of the immune system,
      which is responsible for protecting the organism, to this bacteria and the
      duodenal tissue damage. The aims of our study were to examine the expression of
      class I and II MHC receptors in the immune cells in the peripheral venous blood
      of patients with chronic active gastritis and duodenal ulcer. METHODS: The study
      included a total of 124 cases (Helicobacter pylori-positive patients without
      prior treatment, 47 of whom had small-sized and 56 medium-sized duodenal ulcer,
      and 21 healthy individuals). Immune cells carrying receptors CD3, CD4, CD3/4,
      CD8, CD3/8, CD14, CD45, CD14/45, HLA-DR, CD3/HLA-DR, CD16/56, and CD3/16/56 by
      applying DAKO Dual Color Reagent, and non-specific indicators of reactivity, were
      investigated in the peripheral venous blood samples. RESULTS: In both study
      groups, nonspecific indicators of reactivity in peripheral venous blood were not
      different from those in the healthy group irrespective of the ulcer size. It was
      detected that NK cells which express only CD3/16/56 receptor are more aggressive
      than class I MHC carriers, which were increased in both patient groups more
      markedly than in the control group (p<0.05). The number of CD14 cells in patient
      groups with small- and medium-sized duodenal ulcers was found to be lower than in
      the control group. This difference was more marked in the small-sized ulcer group
      than in the medium-sized ulcer group. While there was a similarity in the number
      of CD45 cells in all three groups, the number of CD14/45 cells was reduced in the
      study group. This reduction was found statistically insignificant in the medium
      sized ulcer group, but significant in the small-sized ulcer group (p<0.05). As
      compared to the control group, the number of HLA-DR cells was found to be
      increased in both study groups, and CD3/HLA-DR was found to be increased in the
      medium-sized ulcer group (p<0.05). CONCLUSIONS: The reduced number of CD14 cells
      may have been among the factors predisposing to the development of Helicobacter
      pylori infection. Such a deficit in cellular defense may be compensated through
      the upregulation of cells with HLA-DR and CD3/HLA-DR markers by the organism. The
      increase in the number of cells expressing CD3/16/56 in chronic antral gastritis
      and duodenal ulcer patients positive for Helicobacter pylori suggests a role for
      autoimmune events in these diseases.

PMID- 14655060
TI  - HCV prevalence in Hodgkin and non-Hodgkin lymphoma cases.
AB  - BACKGROUND/AIMS: In this study we aimed to investigate the relation between
      hepatitis C virus (HCV) and B cell lymphoproliferative diseases. METHODS: Eighty
      four patients with B-cell non-Hodgkin lymphoma and 50 patients with Hodgkin
      lymphoma were included. Control group consisted of another 100 otherwise healthy
      blood donors who had no previous history of invasive surgery, blood transfusions,
      and viral hepatitis. HCV positivity was investigated in both case groups and
      control group. RESULTS: Anti-HCV positivity was significantly more frequent in B
      cell non-Hodgkin lymphoma patients compared to control group (7.1% vs. 1%,
      p<0.05). In Hodgkin lymphoma patients however, frequency was comparable with the
      control group (2% vs. 1%, p<0.05). CONCLUSIONS: These findings suggest that HCV
      may play a role in the development of B-cell non-Hodgkin lymphoma, but not in
      Hodgkin lymphoma.

PMID- 14655061
TI  - The use of tissue polypeptide specific antigen as a marker in liver diseases.
AB  - BACKGROUND/AIMS: Tissue polypeptide specific antigen was first defined by
      Bjorklund in 1957 and is the specific M3 epitope of tissue polypeptide antigen.
      It is increased in malignant as well as in some benign diseases. The level of
      tissue polypeptide specific antigen in serum is related mostly with proliferation
      capacity rather than with tumor mass and cell necrosis. The aim of this study was
      to evaluate the levels of tissue polypeptide specific antigen and other tumor
      markers in patients with liver cirrhosis, chronic active hepatitis and hepatoma
      to determine if tissue polypeptide specific antigen is superior to other tumor
      markers in hepatoma patients. METHODS: Thirty-seven patients and 20 controls were
      included in the study. The patients were divided into three subgroups as
      cirrhosis, hepatoma and chronic active hepatitis. The levels of tissue
      polypeptide specific antigen, carcinoembryonic antigen, CA19-9, alpha-fetoprotein
      and transaminases were determined in all patients. RESULTS: Tissue polypeptide
      specific antigen levels were significantly higher in all patients than in the
      control group (p<0.005) According to Kruskal-Wallis test with regard to
      subgroups, the differences in mean values of tissue polypeptide specific antigen
      and alpha-fetoprotein were highly significant (p: 0.0001 for both). There was a
      low correlation between tissue polypeptide specific antigen and alpha-fetoprotein
      in the cirrhotic and hepatoma groups, but these were significantly correlated in
      the chronic active hepatitis group. The correlation coefficient between tissue
      polypeptide specific antigen and transaminases in all patients was low.
      CONCLUSIONS: Our data suggest that tissue polypeptide specific antigen is
      efficient in determining primary hepatoma patients and also that this marker is
      specific for proliferation of cells.

PMID- 14655062
TI  - Are serum and biliary carcinoembryonic antigen and carbohydrate antigen19-9
      determinations reliable for differentiation between benign and malignant biliary
      disease?
AB  - BACKGROUND/AIMS: The value of serum tumor markers carbohydrate antigen 19-9 (CA19
      9) and carcinoembryonic antigen (CEA) in the differential diagnosis of
      obstructive biliary disease is dubious. We aimed to define their usefulness
      prospectively. METHODS: Thirty-seven consecutive patients (12 female, 25 male,
      median age: 54, range: 19-83 years) who were referred for endoscopic retrograde
      cholanugiopancreatography (ERCP) or percutaneous transhepatic cholangiography
      (PTC) examination for obstructive jaundice were included (all with dilatation of
      biliary tree in ultrasonography or computerised tomography). Bile was obtained
      through the nasobiliary or external drainage catheter, placed with ERCP or PTC,
      respectively. Serum samples were taken from all patients at the time of
      acquisition of bile. Serum and bile samples were stored at -50 oC until they were
      tested. CA19-9 and CEA levels were measured with chemiluminescent enzyme
      immunoassay methods in serum and bile samples by using immulite GI-MA and CEA
      commercial kits, respectively (DPC(r), Los Angeles). RESULTS: In 22 patients with
      malignant disease, serum CEA levels were 38.6+/-115.8 ng/ml and CA19-9 were
      386.9+/-409.7 U/ml, while in 15 patients with benign disease the serum CEA levels
      were 1.8+/-1.6 ng/ml and CA19-9 were 128.9+/-302.2 U/ml. The difference for both
      values was significant (p<0.05). In malignant disease bile CEA and CA19-9 levels
      were 160.8+/-457.8 ng/ml, 14000.9+/-19798 U/ml respectively, while in benign
      disease the corresponding levels were 21.08+/-48.6 ng/ml for CEA and 14818.9+/
      24665.7 U/ml for CA19-9. The differences were not significant in this case
      (p>0.05). CONCLUSION: It was concluded that serum CA19-9 levels are increased
      both in malignant and benign obstructive biliary diseases, albeit more
      significantly in the former. However, increase in serum CEA is mostly restricted
      to malignant diseases. Measurement of these markers in bile is of no value.

PMID- 14655063
TI  - Tissue transglutaminase expression in duodenal mucosa of patients with celiac
      disease and of normal subjects.
AB  - BACKGROUND/AIMS: Our aim in the present study was to investigate tissue
      transglutaminase expression by immunohistochemistry in duodenal mucosa of
      patients with celiac disease. METHODS: A total of twelve patients with celiac
      disease were examined. The patients had different clinical and histopathologic
      degrees of severity and responded to gluten withdrawal with clinical improvement.
      Ten subjects with various unrelated diseases served as controls. Serum endomysium
      antibodies were measured by an indirect immunofluorescence method using a
      commercial kit. Duodenal biopsy specimens were stained with hematoxylin and
      eosin. Immunohistochemical staining for anti-tissue transglutaminase antibodies
      was performed using commercial kit. RESULTS: Serum endomysium antibodies and
      evaluation of small bowel biopsy specimens were normal in all control subjects.
      However, serum endomysium antibodies were positive in all of the celiac patients.
      Immunohistochemical staining pattern of duodenal biopsy specimen performed using
      anti-tissue transglutaminase antibodies was similar in celiac patients and
      control subjects. CONCLUSION: Tissue transglutaminase expression by
      immunohistochemical methods in untreated celiac mucosa is not suitable for
      diagnosis of celiac disease.

PMID- 14655064
TI  - Emergency bowel surgery in the elderly.
AB  - BACKGROUND/AIMS: Emergency bowel operations are commonly performed in emergency
      units and carry high morbidity and mortality risk, particularly in elderly
      patients. The aim of the present study was to review the presentation, management
      and outcome of bowel emergencies in elderly patients. METHODS: The records of 248
      patients (91 females, 157 males) aged over 65 years, undergoing emergency bowel
      operation during a five-year period, were reviewed. Patient's age, sex, details
      of presentation, past medial history, presence of coexisting diseases, and type
      of surgical procedures were noted, and their effects/any unfavorable outcomes
      were all analyzed. Data were evaluated by using SPSS 9.0 for Windows statistical
      program. A p value less than 0.05 was accepted as significant. RESULTS: Mean age
      was 72.5 years. There were 85 (34%) isolated small bowel emergencies (SBE) and
      153 (62%) isolated large bowel emergencies (LBE). The most common disease in SBE
      was mesenteric ischemia in 67 (27%), followed by adhesions, 26 (10%). Malignant
      bowel disease in 59 (24%) and sigmoid volvulus in 43 (17%) accounted for the
      majority of LBE. Sixty-five percent (161) of patients presented with obstruction
      and 46 (19%) patients had bowel perforation. Malignant disease, volvulus and
      mesenteric ischemia carried high resection rates (82%, 78% and 76%,
      respectively). Overall morbidity and mortality rates were 42% (105) and 28% (70),
      respectively. CONCLUSIONS: Emergency bowel operations have poor outcome in the
      elderly. Nature and extent of disease, presence of coexisting cardiopulmonary
      disease, late admission and presence of peritonitis significantly affect
      management and outcome of elderly patients with bowel emergencies.

PMID- 14655065
TI  - Type 1 gastric carcinoid tumor: another extrahepatic manifestation of hepatitis C
      virus infection?
AB  - A 67 year-old female with a 10-year history of cirrhosis due to hepatitis C virus
      who developed a gastric carcinoid tumor of the corpus is described. Carcinoid
      tumor was identified during her last routine gastroscopic evaluation for portal
      hypertension. In the case, serum parietal cell antibodies, hypergastrinemia and
      atrophic gastritis were also found. Chronic hepatitis C virus infection is known
      to induce clinical and laboratory signs of autoimmunity. But the question of
      whether hepatitis C virus plays a pathogenic role in the development of gastric
      carcinoid tumor is unknown. As far as we know, this is the first report
      describing gastric carcinoid tumor in hepatitis C virus induced chronic liver
      disease. We suggest that the possibility of the development of autoimmune
      atrophic gastritis and carcinoid tumors should be considered in patients with
      chronic hepatitis C that coexists with autoimmune diseases and has positive
      parietal cell antibodies.

PMID- 14655066
TI  - Is celiac sprue an etiology of amyloidosis?
AB  - Gluten-sensitive enteropathy is a chronic disease due to malabsorption, and
      chronic inflammatory disorders may be a cause of secondary amyloidosis. We hereby
      report the first case with diagnosis of amyloidosis and gluten-sensitive
      enteropathy.

PMID- 14655067
TI  - Atypical presentation of chronic pancreatic fistula: a case successfully managed
      with long-acting somatostatin.
AB  - Pancreatic fistula is a potential complication of trauma or inflammation of the
      pancreatic duct or accessory pancreatic ducts. These fistulous tracts tend to
      form external to the pancreas; internal cases are rare. Pharmacological
      inhibition of pancreatic exocrine secretion and conservative approaches such as
      percutaneous endoscopic interventions are widely used to treat pancreatic
      fistulae. However, these fistulae are still associated with significant mortality
      and morbidity. In this report, we describe a case with post-splenectomy
      pancreatic fistulae and related recurrent abdominal abscess who was successfully
      managed with long-acting somatostatin.

PMID- 14655068
TI  - A case of autoimmune hepatitis and autoimmune hemolytic anemia following
      hepatitis A infection.
AB  - Hepatitis A infection is known to induce autoimmune hepatitis and autoimmune
      hemolytic anemia. Here we present a case with autoimmune hepatitis type I and
      autoimmune hemolytic anemia following hepatitis A virus (HAV) infection. CASE:
      M.A., a male patient, was brought to the hospital with complaints of jaundice and
      malaise. Physical examination revealed paleness and icterus. The liver was
      palpable 5 cm below the costal margin in the midclavicular line; the spleen was
      palpable 2 cm from the costal margin. Laboratory examination revealed severe
      anemia, reticulocytosis and direct Coombs' IgG positivity. Liver enzymes, total
      and conjugated bilirubin and alkaline phosphates levels, total protein and
      immunglobulin levels were high and prothrombin time elongated. Hepatitis A IgM
      antibody was found positive, while other hepatitis serologic markers were
      negative. Anti-smooth muscle antibody (ASMA) was positive in 1/80 titer. With
      these laboratory findings, the case was diagnosed as autoimmune hepatitis and
      autoimmune hemolytic anemia induced by hepatitis A infection. Liver histology
      also supported the diagnosis. Steroid therapy resulted in clinical and laboratory
      remission. In conclusion, it is important to vaccinate children against hepatitis
      A infection to protect them from its complications and also from autoimmune
      diseases induced by this infection.

PMID- 14655069
TI  - Nimesulide-induced fulminant hepatitis.
AB  - An 18-year-old boy was brought to the hospital with jaundice, confusion,
      abdominal discomfort and distension. He had a history of oral intake of
      nimesulide for three days. Clinical and laboratory findings were compatible with
      fulminant hepatitis. Exclusion of other causes of liver injury strongly favored
      drug-induced toxicity. All of the signs, symptoms and laboratory abnormalities
      returned to normal after cessation of the nimesulide and supportive treatment,
      and he was discharged on the 15th day after admission. This case differs from the
      other cases in the literature regarding the time of onset, and indicates that
      nimesulide may induce fulminant hepatitis in the first few days of
      administration. Therefore, patients receiving nimesulide should be frequently
      monitored with serial serum transaminases, beginning from the first week of
      intake.

PMID- 14655070
TI  - Clear cell carcinoma of the liver: a case report.
AB  - Hepatocellular carcinoma represents the 8th most frequent malignancy worldwide.
      The World Health Organization recognizes five histologic patterns and four
      cytologic variants of hepatocellular carcinoma. Clear cell carcinoma of the liver
      is a well-defined variant of hepatocellular carcinoma in which a large number of
      cells show clear cytoplasm that does not stain with hematoxylin and eosin. It can
      be confused with other clear-cell malignancies. A 52-year-old man presented with
      mild dyspeptic symptoms, right-sided upper abdominal pain, weakness, weight loss,
      abdominal mass and jaundice symptoms for nearly six weeks. After diagnostic
      procedures, an ultrasonography-guided liver biopsy was performed. In microscopic
      examination, malignant cells with vacuolated foamy to clear cytoplasm and central
      and eccentric nuclei, tumor composed of solid mass and cords, and clear cells
      were observed, and hepatocellular carcinoma, clear cell variant, is diagnosed. We
      report this rare case of primary clear cell carcinoma in the cirrhotic liver. The
      case was discussed in detail regarding histological presentation, with particular
      attention to histopathologic differential diagnosis.

PMID- 14655071
TI  - Sickle cell anemia connected with chronic intrahepatic cholestasis: a case
      report.
AB  - Sickle cell anemia is a disease caused by production of abnormal hemoglobin,
      which binds with other abnormal hemoglobin molecules within the red blood cell to
      cause rigid deformation of the cell. This deformation impairs the ability of the
      cell to pass through small vascular channels. Sludging and congestion of vascular
      beds may result, followed by tissue ischemia and infarction. Liver injury can be
      caused by the adherence of deformed or hemolyzed erythrocytes to hepatic vascular
      endothelium. Adhesion of large numbers of hemolyzed red blood cells to hepatic
      macrophages, or occlusion of hepatic sinusoids by fragmented red cells, can also
      result in injury of the liver. Chronic intrahepatic cholestasis is an uncommon
      complication in patients with sickle cell disease. The findings in this case
      suggest that therapeutic erythrocyte apheresis may benefit patients who have
      unusual complications of sickle cell disease, such as chronic intrahepatic
      cholestasis in the liver.

PMID- 14655073
TI  - [Colorectal carcinoma: prevention instead of suffering].

PMID- 14655074
TI  - [The medical dissertation--no definitive model. Results of a survey about
      obtaining a doctorate contradict frequently stated opinions].
AB  - BACKGROUND AND OBJECTIVE: The relevance of medical dissertations is controversial
      in Germany. The "Wissenschaftsrat" (Science Council) of Germany even made the
      radical proposal of abolishing medical dissertations, in their present form, in
      the recently published "Guidelines on writing a thesis". METHODS: Using a
      questionnaire with 22 items all students submitting their dissertations within
      one year at the Medical School in Hannover were asked to participate in a survey
      about the dissertation, supervision, time spent on it and publishing the results.
      The answers were evaluated statistically by explorative data analysis. RESULTS: A
      total of 232 questionnaires were evaluated, which is equivalent to a response
      rate of 87% (47% were women). A majority of 69% had prepared their thesis in a
      clinical institution. The supervision during various phases of the dissertation
      was graded as good. Altogether 90% thought that it had been personally worth
      while. In 57% of cases the data of the dissertation had already been published
      and in 39 % of these cases the author of the dissertation was listed as first
      author of the publication. CONCLUSIONS: In agreement with former studies in
      German universities an overwhelming majority of 90% of respondents graded
      dissertations as a significant part of their medical studies, although requiring
      much additional time. They would recommend such a research phase to younger
      students as highly valuable. These results are in contrast to many repeatedly
      made statements.

PMID- 14655075
TI  - [Prerenal kidney failure in type 1 diabetes mellitus].
AB  - HISTORY AND ADMISSION FINDINGS: A 22-year-old man was admitted in a severely
      reduced condition. Type 1 diabetes mellitus had been diagnosed when he was 13
      years old, hypothyroidism was treated with L-thyroxine for 2 years. For the past
      3 years he suffered from repetitive hypoglycemia, combined with vertigo, weakness
      and low blood pressure. INVESTIGATIONS: He presented with hypotension and
      hyperpigmentation of the skin. Pathological laboratory results were: serum
      creatinine 2.5 mg/dl; urea 145 mg/dl; sodium 124 mmol/l; potassium 8.3 mmol/l,
      HbA (1c) 9.1%. The ECG showed large T waves. Additionally, plasma aldosterone was
      decreased (<10 ng/l), plasma renin was increased (2404 ng/l), basal serum
      cortisol was decreased (16.1 microg/l). No increase of plasma cortisol after i.
      v. stimulation with ACTH (1-24) occurred. Plasma ACTH was increased to 630 pg/ml.
      Test for adrenal autoantibodies were positive. DIAGNOSIS: Primary adrenal
      insufficiency with prerenal renal failure. Autoimmune polyglandular syndrome
      (APS) type II with Addison's disease, diabetes mellitus type 1 and hypothyroidism
      (Schmidt-Carpenter-Syndrome) were diagnosed. TREATMENT AND COURSE: Initially, the
      patient was treated with sodium chloride 0.9% i. v. and oral sodium 5 g 4
      times/day. In addition, he was given hydrocortisone 100 mg i. v., and then
      switched to 40 mg per day (20-10-10 mg), fludrocortisone 0.05 mg/ day and L
      thyroxine 75 microg/ day orally the clinical condition improved dramatically
      within 24 hours. Intensified conventional insulin therapy was continued.
      CONCLUSION: In patients with type 1 diabetes, especially in combination with
      associated organ-specific autoimmune diseases, autoimmune polyglandular syndrome
      should be considered and adequately treated with those hormones that are reduced.

PMID- 14655076
TI  - [Hereditary hemorrhagic teleangiectasia (Osler-Weber-Rendu disease)].

PMID- 14655077
TI  - [Evidence-based prevention of colorectal carcinoma].

PMID- 14655078
TI  - [Horton's temporal arteritis (giant cell arteritis). Pioneering work and present
      status].

PMID- 14655079
TI  - [The role of the physician in our society].

PMID- 14655080
TI  - [Is there a connection between tooth diseases and diseases in a healthy heart?].

PMID- 14655081
TI  - [A new method for the evaluation of stone fragmentation after ESWL].
AB  - INTRODUCTION: Efficacy of ESWL treatment can be evaluated by determining the
      number and size of urinary stone fragments. However, the available methods for
      classification of stone fragments are inaccurate. Therefore, a method for semi
      automatic determination of fragment size and number after ESWL was developed.
      METHODS: Artificial struvite stones (BON[N]-STONES) were disintegrated with a
      lithotriptor (Siemens, Lithostar plus) by application of 50 and 200 shock waves
      at 19 kV. The stone fragments were collected and pre-sorted on cascade sieves.
      Pictures taken of the fractions were digitalized and the images optimized in edge
      sharpness, contrast, and colour depth using an image processing software.
      Finally, the pixel number of each fragment was determined and the real area was
      calculated. Fragment size and volume were then depicted by frequency of
      occurrence in a histogram. RESULTS: Fragments with a diameter ranging from 0.3 -
      5 mm could be determined by the system described. About 2,000 - 3,600 fragments
      were generated in this size range from the artificial struvite stones. With low
      shock-wave application, a considerable number of fragments larger than 2 mm could
      be observed. By increasing the impact to 200, more than 90 % of the stone volume
      was found in fragments smaller than 2 mm (previously 50 %). CONCLUSION: The
      system described enables a qualitative and quantitative description of stone
      fragmentation after ESWL not achieved thus far.

PMID- 14655082
TI  - [Basics of antisense oligonucleotide therapy and current therapeutical strategies
      in urology].
AB  - Antisense oligonucleotides are short DNA sequences designed to modulate the
      information transfer from gene to protein. Sequence-related hybridisation with
      the mRNA of a specific protein results in selective inhibition of gene expression
      and downregulation of protein expression. This allows the study of gene function
      and therapy on a molecular level. Antisense oligonucleotide inhibitors can be
      designed directly from genomic sequence information by simply making the reversed
      complement of the desired sequence. In this review, we focus on the mechanisms of
      action of antisense oligonucleotides and summarize the progress in urological
      antisense therapy. The ability to inhibit individual gene expression with
      antisense oligonucleotides has been promising in preclinical cancer models.
      Current clinical studies test antisense compounds targeted against various cancer
      related genes. Although some of these studies comprise patients with urological
      tumors, such as advanced prostate cancer, experimental antisense therapy in
      urology is still in its infancy.

PMID- 14655083
TI  - [Impact of tumor size on long-term survival of patients with organ-confined renal
      cell cancer].
AB  - PURPOSE: As a result of the observation that the potential biological
      aggressiveness of even early stage renal cell cancer (RCC) strongly correlates
      with tumor size, the 5th edition of the TNM system (1997), which classifies all
      renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current
      classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only
      a few larger investigations supporting this cut-off are available in the
      literature and these are based on univariate statistical analysis. To determine
      whether this cut-off best reflects the correlation between aggressive potential
      and tumor size and thus differentiates patients at low or high risk of
      progression, this investigation was performed using both univariate and
      multivariate statistical analysis. MATERIALS AND METHODS: Between 1981 and 2000,
      a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of
      these, the 243 patients with local RCC not extending beyond the renal capsule
      were subjected to univariate (log rank test) and multivariate (Cox regression
      model) statistical analysis. RESULTS: It became evident that, while during
      univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed,
      multivariate analysis identified the highest relative risk of cause-specific
      death (2.93) in those patients with tumors larger than 5 cm maximum diameter.
      CONCLUSIONS: The 5 cm cut-off thus appears to best determine the clinical
      prognosis for patients undergoing tumor nephrectomy for early stage renal call
      cancer. Taking this into consideration, the present study clearly demonstrates
      the reed for a multivariate statistical approach when the current modification of
      the TNM classification system is critically reevaluated.

PMID- 14655084
TI  - [Percutaneous embolization of the kidney: indications and clinical results].
AB  - OBJECTIVE: Renal embolisation offers a minimal invasive means of renal ablation
      under primary palliative indication. We evaluated our experience with this
      technique in a series of 40 patients. PATIENTS AND METHODS: From 1996 to 2002 a
      total of 40 patients underwent total embolisation of the kidney. Our patients
      encompassed 15 females and 25-males (median age: 68 years, 46 - 89 years). In 15
      patients indication for embolisation was to ablate a non-functioning kidney
      following obstruction due to advanced cancer, in 9 patients preoperatively with
      advanced renal cell carcinomas invading the vena cava, in 8 patients for control
      of hematuria and in 8 patients with non-operable advanced renal cancers. The
      embolisation was carried out in DAS-technique with a 7 Fr. selective catheter and
      central placement of macrocoils, from 2000 on we additionally performed a
      peripheral embolisation with polyvinylalcohol (PVA) particles. The intervention
      took place in epidural anesthesia. RESULTS: Perioperatively in all patients a
      complete occlusion of the renal artery as well as acessory arteries (n = 6) could
      be documented radiographically, perioperative complications were not observed. A
      post-embolisation syndrome occured in 32 patients. Reinterventions with repeat
      embolisation became necessary in 5 patients (persistent urine production-n = 4,
      persistent hematuria-n = 1). SUMMARY: The combined central and peripheral
      embolisation of the kidney in epidural anesthesia is a valuable means in selected
      patients under palliative indication for defunctionalisation of the kidney as
      well as control of hematuria.

PMID- 14655085
TI  - [Tunica plication with horizontal incisions of the tunica albuginea in the
      treatment of congenital penile deviations].
AB  - PURPOSE: The Schroeder-Essed plication procedure is a standard technique for the
      correction of penile curvature. In a retrospective analysis we compared
      functional results and quality of life of the original technique with inverted
      sutures as described by Schroeder-Essed and our slight modification consisting of
      horizontal incisions into the tunica albuginea. MATERIALS AND METHODS: A total of
      26 patients with congenital penile deviation were treated, 11 by the original
      Schroeder-Essed plication with inverted sutures and 15 using the described
      modification. In the modified technique, horizontal and parallel incisions 4 mm -
      6 mm apart and about 8 mm - 10 mm long were made through the tunica albuginea.
      The outer edges of the incisions were then approximated with permanent inverted
      sutures (Gore-Tex(R) 3-0). Mean age was 21.6 years in the first group and 23.2
      years in the second group. The preoperative penile deviation angle was > 25
      degrees in all patients without differention between the two groups. RESULTS: All
      patients in both groups reported improvement in their quality of life and full
      ability to engage in sexual intercourse. A total of 9 patients (88 %) in the
      first group and 14 patients (93 %) in the second group were satisfied with the
      cosmetic result, although 10 patients (91 %) in the first and 13 patients (87 %)
      in the second group complained of penile shortening. Recurrence of deviation was
      only observed in 2-males in the first group (18 %). CONCLUSIONS: Our results
      indicate that this simple modification of the Schroeder-Essed plication offers
      good functional and cosmetic results. Most patients were satisfied with the
      penile angle correction results.

PMID- 14655086
TI  - [Infected upper renal pole in a duplex system with paravaginal abscess].
AB  - INTRODUCTION: Diagnosis of afunctional duplex systems may be delayed as they are
      often associated with misleading and atypical symptoms. A 40-year-old female with
      no history of urological disease exemplifies this thesis. CASE REPORT: Symptoms
      at admission were fever with pain in the right flank and lower abdomen.
      Sonography showed a large unclear structure at the upper pole of the right kidney
      and a paravaginal abscess, which was drained primarily. Rising temperature led to
      examination by CT-scan, which revealed a renal abscess of the upper pole,
      suggesting a right extopic ureter. After percutaneous drainage, further
      examinations (antegrade pyelography and IVP) confirmed an ectopic, blind-ending
      duplex ureter with a hydropyonephrotic upper renal system on the right side.
      Upper poole resection with ureterectomy was performed. CONCLUSIONS: In patients
      with unclear abscesses in the area of the external genitalia, congenital
      anomalies of the urinary tract should be considered as an underlying disease.

PMID- 14655087
TI  - [Congenital prepubic sinus: etiology and therapy].
AB  - INTRODUCTION: Congenital prepubic sinus (CPS) is a rare diagnosis. It is defined
      as a blind-ending tract originating from the midline of the genital region. There
      are three types of CPS classified according to the course of the tract and
      location of the skin opening. The etiology is thought to be an intussusception
      during fusion of the abdominal wall or, alternatively, incomplete urethral
      duplication. CASE REPORT: We report on a two-year-old boy with a skin fistula on
      the dorsal side of the penis. A slight secretion occurred when the surrounding
      subcutaneous tissue was compressed. After total resection of the sinus,
      histological examination revealed that the tract was lined primarily with
      multilayered epithelium. Immunohistochemical studies showed that the sinus was
      lined with transitional and squamous epithelium. At the base the lining
      epithelium was transitional and shifted distally to noncornifying squamous
      epithelium. The epithelial layer therefore corresponded to the inner surface of
      the urethra, thus supporting the assumption that CPS results from incomplete
      urethral duplication. CONCLUSION: The immunohistochemical examination of the
      epithelium of Type II CPS proved, in this case, the existence of urothelium as
      the inner surface of the sinus. In view of this evidence it appears likely that
      the congenital prepubic sinus can be classified etiologically as an incomplete
      urethral duplication.

PMID- 14655088
TI  - [The iatrogenic fornix rupture after endoscopic extraction of an ureteral stone
      via ureterorenoscopy].
AB  - Iatrogenic fornix rupture caused during retrograde manipulation of the ureter is
      a rather rare or rarely diagnosed phenomenon. A 22 year-old female patient
      presented with fornix rupture following endoscopic ureteral stone extraction
      under ureterorenoscopy, the rupture having become symptomatic 2 days later.
      Diagnostics were done by means of sonography and radiography and confirmed by CT
      scan performed to rule out abscess formation which may have occurred in this case
      of delayed symptoms. Conservative antibiotic therapy was sufficient in this case.
      Ca. 10 % of all perirenal abscesses are attributed to urinary extravasation due
      to fornix ruptures, requiring surgical intervention. Regular sonographic control
      is therefore strongly recommended when fornix rupture is suspected to ensure
      appropriate counter measures.

PMID- 14655089
TI  - Bronchoesophageal fistula in a neonate: radionuclide study as diagnostic
      modality.
AB  - A neonate with H-type fistula between esophagus and right bronchus is described.
      He presented with an uncommon symptom of hypersialosis. The fistula was missed
      both at cinesophagogram and endoscopy, the modalities currently held as
      investigations of choice for the diagnosis of this entity. Instead it was
      incidentally picked up by radionuclide study undertaken to rule out dyskinesia or
      gross gastroesophageal reflux, which demonstrated the tract unequivocally. To the
      best of our knowledge this modality has not been used earlier for this purpose.
      The authors feel that although persistence in attempts to demonstrate the tract
      preoperatively is important, radionuclide study can also be considered as a
      diagnostic tool in difficult cases.

PMID- 14655090
TI  - Severe neutrophilia in an infant with persistent pulmonary hypertension of the
      newborn.
AB  - We report the case of a term male infant with severe persistent pulmonary
      hypertension of the newborn, who developed massive neutrophilia of unknown
      etiology. An extensive evaluation failed to disclose an obvious cause for his
      neutrophilia. A bone marrow aspirate was performed and was consistent with a
      leukemoid reaction. This paper reviews the neonatal leukemoid reaction and its
      significance.

PMID- 14655091
TI  - Placenta previa: does its type affect pregnancy outcome?
AB  - Our objective was to compare pregnancy outcomes associated with different types
      of placenta previa. This is a retrospective analysis of pregnancies complicated
      by placenta previa, from January 1990 to December 1997. Descriptive statistics
      and comparison analyses were performed. One hundred seventy-five singleton
      pregnancies beyond 24 weeks that were complicated by complete, partial, or
      marginal previa were included. Differences in pregnancy outcomes between
      complete, partial, and marginal previas were: onset of bleeding (29.9 +/- 4.5
      versus 32.5 +/- 6.9 versus 32.7 +/- 5.0 weeks, respectively, p < 0.05),
      antepartum hospitalization (60.7% versus 38.1% versus 35.1%, respectively, p <
      0.05), gestation at delivery (34.7 +/- 3.1 versus 37.4 +/- 2.6 versus 36.1 +/-
      3.0 weeks, respectively, p < 0.05), birth weight (2498.3 +/- 746.8 versus 2978.8
      +/- 568.3 versus 2813.4 +/- 728.4 g, respectively, p < 0.05), and hysterectomy at
      time of cesarean delivery (20.5% versus 0% versus 8.1%, respectively, p < 0.05).
      For all outcome parameters, the partial and marginal previa groups did not
      differ. Women with complete placenta previa, as diagnosed with modern ultrasound
      techniques, had poorer pregnancy outcome. They were more likely to deliver
      prematurely and were more likely to require a hysterectomy at the time of
      cesarean delivery.

PMID- 14655092
TI  - Fetal DNA levels in maternal blood correlated with fetal prognosis in a case of
      intervillous hematoma.
AB  - Several methods for detection of fetal components in maternal blood have been
      reported. However, few have proven clinically useful for determining the
      treatment in cases of placental injuries. Here, we report a case of extensive
      intervillous hematoma diagnosed at 25 weeks of gestation with severe intrauterine
      growth restriction and oligohydramnios. Marked elevation of fetal DNA levels was
      observed in maternal blood. Fetal DNA levels decreased after 27 weeks of
      gestation, concurrent with recovery of fetal growth. We conservatively managed
      this case until 30 weeks of gestation, when a male infant was delivered. He
      weighed 508 g and displayed Apgar scores of 7 at 1 minute and 9 at 5 minutes.
      Histological examination of the placenta revealed intervillous thrombosis without
      infarction or inflammatory changes. In this case, decreasing fetal DNA levels in
      maternal plasma correlated with recovery of fetal growth and provided useful
      information for fetal management as well as insight into the pathogenesis of
      placental injuries.

PMID- 14655093
TI  - Labor does not affect the neonatal absolute nucleated red blood cell count.
AB  - We investigated whether the presence or absence of physiologic labor may affect
      the neonatal nucleated red blood cell (RBC) count. We compared absolute nucleated
      RBC counts taken at approximately 6 hours of life in term infants born by
      elective cesarean delivery without trial of labor ( n = 32) and in vaginally
      delivered infants ( n = 28). Venous blood samples were analyzed and differential
      cell counts were performed manually; absolute nucleated RBC were counted and
      expressed as an absolute number. There were no significant differences between
      groups in birth weight, gestational age, maternal age, gravidity, parity,
      maternal analgesia during labor, 1- and 5-minute Apgar scores, and infant sex.
      There was a significantly higher hematocrit and RBC count in the vaginally
      delivered group as compared with the cesarean group. The absolute nucleated RBC,
      corrected leukocyte and lymphocyte, and platelet counts were strikingly similar
      in both groups. We conclude that labor does not affect the neonatal nucleated RBC
      count. This finding supports the speculation that physiologic labor does not
      induce a fetal hypoxemia severe or prolonged enough to produce hematological
      evidence of increased erythropoiesis.

PMID- 14655094
TI  - Whose child is it anyway? Resolving parent-physician conflict in the NICU
      setting.
AB  - Much has been written on parental involvement in decision making when dealing
      with critically ill children, but few articles have touched upon parental refusal
      of treatment in noncritically ill children. What steps should be taken when a
      parent refuses what is generally considered "standard of care" medicine for their
      hospitalized child? Does medical advice outweigh parental views or wishes, and
      what does one do when our role as physician turns from medical expert into one of
      medical negotiator? The following case and discussion deal with parental refusal
      of conventional medical care, and how one may find peaceful resolutions to
      challenging situations for the ultimate good of the child.

PMID- 14655095
TI  - Outcome of prolapsed chorioamniotic membrane: relationship between the degree of
      herniation, infection, and pregnancy prolongation.
AB  - Our objective was to determine the outcome predictor of conservative bed rest
      therapy for prolapsed chorioamniotic membrane. We could perform tocolysis for 61
      women, 41 of visible membrane (group A) and 20 of protruding membrane (group B).
      The duration of pregnancy prolongation and gestational age (in weeks) at delivery
      in group A were significantly larger than in group B ( p < 0.05). Outcome of
      neonates was also significantly different between two groups ( p < 0.05). In 37
      women of group A (90%) and 10 of group B (50%; group D), signs of infection were
      negative throughout the admission to delivery with conservative therapy (white
      blood cell counts </= 13000/microL and CRP values </= 1.0 mg/dL). In group D,
      pregnancy was prolonged 23.9 days, which was significantly longer than in group B
      ( p < 0.05). This study suggests that pregnancy prolongation for prolapsed
      membrane with conservative therapy depends on the success of prophylactic
      treatment for infection.

PMID- 14655096
TI  - Fetal Diamond-Blackfan anemia associated with hydrops fetalis.
AB  - We present a case of fetal Diamond-Blackfan anemia (DBA) associated with hydrops
      fetalis and review the current literature focusing on the pathophysiology and
      presentation of DBA. We conclude that DBA should be considered as a possible
      etiology for fetal anemia even in the absence of a family history of anemia.

PMID- 14655097
TI  - Further evidence of IBD5/CARD15 (NOD2) epistasis in the susceptibility to
      ulcerative colitis.

PMID- 14655098
TI  - Reports of the death of the epistasis model are greatly exaggerated.

PMID- 14655099
TI  - Affected-sib-pair data can be used to distinguish two-locus heterogeneity from
      two-locus epistasis.

PMID- 14655101
TI  - Creatinine in the dog: a review.
AB  - Creatinine is the analyte most frequently measured in human and veterinary
      clinical chemistry laboratories as an indirect measure of glomerular filtration
      rate (GFR). Although creatinine metabolism and the difficulties of creatinine
      measurement have been reviewed in human medicine, similar reviews are lacking in
      veterinary medicine. The aim of this review is to summarize information and data
      about creatinine metabolism, measurement, and diagnostic significance in the dog.
      Plasma creatinine originates from the degradation of creatine and creatine
      phosphate, which are present mainly in muscle and in food. Creatinine is cleared
      by glomerular filtration with negligible renal secretion and extrarenal
      metabolism, and its clearance is a good estimate of GFR. Plasma and urine
      creatinine measurements are based on the nonspecific Jaffe reaction or specific
      enzymatic reactions; lack of assay accuracy precludes proper interlaboratory
      comparison of results. Preanalytical factors such as age and breed can have an
      impact on plasma creatinine (P-creatinine) concentration, while many
      intraindividual factors of variation have little effect. Dehydration and drugs
      mainly affect P-creatinine concentration in dogs by decreasing GFR. P-creatinine
      is increased in renal failure, whatever its cause, and correlates with a decrease
      in GFR according to a curvilinear relationship, such that P-creatinine is
      insensitive for detecting moderate decreases of GFR or for monitoring progression
      of GFR in dogs with severely reduced kidney function. Low sensitivity can be
      obviated by determining endogenous or exogenous clearance rates of creatinine. A
      technique for determining plasma clearance following IV bolus injection of
      exogenous creatinine and subsequent serial measurement of P-creatinine does not
      require urine collection and with additional studies may become an established
      technique for creatinine clearance in dogs.

PMID- 14655102
TI  - Validation of a chemiluminescent enzyme immunometric assay for plasma
      adrenocorticotropic hormone in the dog.
AB  - BACKGROUND: The concentration of canine adrenocorticotropic hormone (ACTH) is
      usually determined by radioimmunoassay. However, chemiluminescent assay
      techniques have many advantages for clinical endocrine testing. OBJECTIVES: The
      objectives of this study were to validate a commercially available
      chemiluminescent assay for determination of canine ACTH concentration and to
      determine whether protease inhibitors are appropriate for use in the
      chemiluminescent assay system. METHODS: Biological specificity was evaluated by
      treatment of 3 dogs with ovine corticotropin-releasing hormone (CRH) followed by
      serial measurements of ACTH and by comparison with a previously validated
      immunoradiometric assay. All samples were collected both in the presence and
      absence of aprotinin, a protease inhibitor. The assay was further evaluated by
      measurement of intra-assay precision, interassay precision, and recovery after
      dilution. RESULTS: Baseline ACTH concentrations ranged from 5.6 to 15.3 pg/mL,
      and maximum ACTH concentrations of 158 to 1240 pg/mL were observed 30-60 minutes
      after CRH administration. Plasma samples collected with aprotinin had
      significantly lower ACTH concentrations than did samples collected without
      aprotinin. The intra-assay coefficients of variance (CVs) ranged from 4.1 to
      8.2%, and interassay CVs ranged from 4.6. to 14.8%. Recovery after dilution with
      canine plasma ranged from 93.4 to 103.0% of predicted concentration; however,
      inadequate recovery was observed with other diluents. There was a high
      correlation with the immunoradiometric assay (r =.925) but a significant negative
      bias (-32.9, 95% confidence interval -50.8 to -14.9). CONCLUSIONS: This
      chemiluminescent assay is a valid technique for measurement of ACTH in canine
      plasma. ACTH concentration measured by chemiluminescence is lower than that
      measured by immunoradiometry. Aprotinin decreases the measured concentration of
      ACTH, and this effect should be taken into account when interpreting results.
      Diluents supplied with the kit should not be used for dilution of canine samples.

PMID- 14655103
TI  - Comparative sequences of canine and feline endothelin-1.
AB  - BACKGROUND: Endothelin-1 (ET-1, "mature ET-1") is a potent vasoconstrictor
      peptide that is made along with "big ET-1" from its precursor, preproET-1.
      Increased plasma concentrations of ET-1 and big ET-1 occur with various forms of
      cardiovascular disease in humans. Our laboratory is investigating plasma
      endothelins as diagnostic tests of cardiovascular disease in dogs and cats;
      however, commercial immunoassays designed specifically for use in dogs and cats
      are limited. OBJECTIVE: Amino acid sequences of feline and canine big ET-1 were
      obtained and used to predict antibody cross-reactivity with immunoassay test kits
      from other species. METHODS: Genomic DNA was extracted from peripheral blood and
      total RNA was extracted from canine and feline left ventricles for reverse
      transcription polymerase chain reaction (PCR) and PCR amplification of segments
      of the canine and feline preprohormone containing the big ET-1 sequences. The
      derived amino acid sequences were compared with known big ET-1 and ET-1 sequences
      of several other species, including human, mouse, and rat. RESULTS: Feline and
      canine big ET-1 had 87-97% and 89-100% homology, respectively, with that of other
      mammalian species. Canine ET-1 was identical to human, mouse, and rat ET-1. In
      contrast, the amino acid sequence of feline ET-1 was unique owing to a leucine
      for methionine substitution at position 7. CONCLUSIONS: It is highly likely that
      anti-human and anti-rodent ET-1 antibodies will cross-react with mature canine ET
      1. In contrast, antibodies to mature ET-1 intended for use with feline tissues
      and antibodies to big ET-1 in either dogs or cats may have partial or no cross
      reactivity depending on the peptide sequences used to produce the antibodies.

PMID- 14655104
TI  - Hematology and serum chemistry values of the European brown hare.
AB  - BACKGROUND: Hematology and serum biochemistry values can be useful for evaluating
      the health of populations of captive and free-living European brown hares (Lepus
      europaeus). However, current information is fragmented and incomplete. OBJECTIVE:
      The objective of this study was to determine normal hematology and serum
      chemistry values for a population of captive European brown hares and to
      investigate differences related to sex and age. METHODS: Routine hematology and
      serum chemistry values were determined for 48 captive European brown hares in
      Catalonia (northeastern Spain): 21 young (6 males and 15 females) and 27 adult
      (14 males and 13 females) hares. Blood was obtained by auricular venipuncture
      while animals were physically restrained. Results were expressed as the mean +/-
      SD, and reference intervals were calculated as the mean +/- 2SD. RESULTS: RBC
      count, PCV, concentrations of hemoglobin, total protein, albumin, gamma globulin,
      urea nitrogen, and creatinine, and alanine aminotransferase activity were
      significantly higher in adults than in young hares, and alkaline phosphatase
      activity and total bilirubin concentration were lower. Sex differences were not
      observed. CONCLUSIONS: Hematology and serum chemistry results obtained in this
      study are considered representative for healthy captive European brown hares. A
      single reference interval can be used for values from male and female hares,
      however, age-specific intervals are needed for some analytes.

PMID- 14655105
TI  - A protocol to guide development of a sensitive ELISA for canine erythropoietin.
AB  - BACKGROUND: The determination of canine erythropoietin (EPO) concentration is
      crucial for monitoring the effect of human recombinant (hr) EPO therapy in dogs
      with chronic renal failure. Current assays are not specific for canine EPO and
      not sensitive enough to detect physiologic EPO levels in dogs. OBJECTIVE: The
      objective of this study was to develop a simple and sensitive ELISA for canine
      EPO that could serve as a starting point for developing a commercially available
      assay. METHODS: The ELISA was based on a mouse monoclonal antibody (mAb) and a
      rabbit polyclonal antibody (pAb) using 2 different immunization techniques: gene
      electrotransfer (GET) to generate the pAb and multiple antigen peptides (MAPs) to
      generate the mAb. The ELISA was performed using both EPO obtained from HeLa cells
      transfected with an expression plasmid encoding canine EPO and canine plasma with
      known concentrations of EPO. RESULTS: The ELISA standard curve was linear for
      canine EPO concentrations of 7-66 mU/ml. Coefficients of variation were about
      10%. No cross-reactivity between canine EPO and hrEPO was detected. CONCLUSIONS:
      Using novel GET and MAP technology, we developed a sensitive and specific ELISA
      for canine EPO that can be used to guide future clinical applications for EPO
      detection and monitoring in dogs.

PMID- 14655106
TI  - Guidelines for resident training in veterinary clinical pathology. I. Clinical
      chemistry.
AB  - BACKGROUND: The Education Committee of the American Society for Veterinary
      Clinical Pathology identified a need for improved structure and guidance of
      clinical pathology resident training in clinical chemistry. OBJECTIVES: The
      committee's goal was to develop learning objectives and competencies in
      knowledge, abilities, and skills in clinical chemistry; provide options and ideas
      for training activities; and identify clinical chemistry resources useful for
      clinical pathology faculty, training program coordinators, and residents.
      METHODS: Guidelines were developed and written with the input of Education
      Committee members and peer experts. RESULTS: The primary objectives of clinical
      chemistry training are: 1) to accrue a thorough, extensive, and relevant
      knowledge base of the types, principles, and properties of clinical chemistry
      tests and concepts of pathophysiology in animals; 2) to develop abilities to
      reason, think critically, and exercise judgment in clinical chemistry data
      interpretation, investigative problem-solving, and hypothesis-driven research;
      and 3) to acquire technical and statistical skills important in clinical
      chemistry and laboratory operations. CONCLUSIONS: These guidelines define
      expected competencies that will help ensure proficiency, leadership, and the
      advancement of knowledge in veterinary clinical chemistry and provide a useful
      framework for didactic and clinical activities in resident training programs. The
      learning objectives can readily be adapted to institutional and individual needs,
      interests, goals, and resources.

PMID- 14655107
TI  - Paratracheal cervical mass in a dog.
AB  - A 14-year-old female Welsh Terrier was presented for evaluation of multiple skin
      masses. Two of them were diagnosed as a follicular (epidermal) cyst and a
      sebaceous epithelioma by cytology and histopathology. The third mass was located
      in the subcutis adjacent to the cervical trachea. Clinical findings, thoracic
      radiography, and laboratory results were otherwise unremarkable. Cytologically,
      the cervical mass was characterized by the presence of round to polygonal cells
      with distinct cell borders, mild to moderate anisocytosis, round to oval
      eccentric nuclei with prominent nucleoli, and a variable amount of finely
      granular, eosinophilic cytoplasm. Differential diagnoses included
      endocrine/neuroendocrine tumors such as thyroid adenocarcinoma, medullary thyroid
      carcinoma, carotid body chemodectoma, and parathyroid carcinoma. The mass was
      removed surgically and submitted for histopathologic and immunohistochemical
      examination. Histologically, the mass was composed of rows and nests of densely
      packed cells separated by thin fibrovascular stroma. Neoplastic cells had
      moderate to large amounts of pale eosinophilic dusty or finely vacuolated
      cytoplasm and round to oval nuclei with finely dispersed chromatin and 1 or 2
      small nucleoli. On immunohistochemistry, neoplastic cells were positive for
      chromogranin A, calcitonin, and neuronspecific enolase, and were negative for
      cytokeratin and thyroglobulin. The final diagnosis was medullary thyroid
      carcinoma, an uncommon endocrine tumor of dogs that has cytologic and
      histopathologic features similar to other endocrine and neuroendocrine tumors.
      Immunohistochemistry or immunocytochemistry should be performed to differentiate
      medullary thyroid carcinoma from other endocrine/neuroendocrine tumors of dogs.

PMID- 14655108
TI  - Dermal mass aspirate from a Persian cat.
AB  - A 1-year-old spayed female Persian cat with alopecia and weight loss had numerous
      variably ulcerated dermal nodules. Cytologic examination of an aspirate of one of
      the nodules revealed pyogranulomatous inflammation along with septate hyphae and
      basophilic round bodies, 0.5-1.0 microm in diameter, surrounded by a thin clear
      halo (arthrospores). The cytologic diagnosis was dermatophytic pseudomycetoma.
      Histologically, there were dermal granulomas containing poorly staining, septate
      hyphae with bulbous spores embedded within abundant amorphous eosinophilic
      material (Splendore-Hoeppli reaction), and the histologic diagnosis was
      pseudomycetoma-associated chronic multifocal severe granulomatous dermatitis with
      lymphocytic perifolliculitis and furunculosis. Microsporum canis was cultured
      from the lesion. Pseudomycetomas are distinguished from fungal mycetomas, or
      eumycotic mycetomas, by the findings of multiple lesions, lack of a history of
      skin trauma, an association with dermatophytes, most commonly Microsporum canis,
      and, histologically, lack of true cement material and a more abundant Splendore
      Hoeppli reaction in pseudomycetomas. Additionally, pseudomycetomas differ from
      dermatophytosis, in which lesions are restricted to epidermal structures. Persian
      cats have a high incidence of pseudomycetoma formation, suggesting a heritable
      predisposition. The prognosis is fair with systemic antifungal therapy. When
      examining cytologic specimens from Persian cats with single or multiple dermal
      nodules, especially if pyogranulomatous inflammation is present, a diagnosis of
      pseudomycetoma should be suspected and is warranted if arthrospores and
      refractile septate hyphae are present.

PMID- 14655109
TI  - Dendritic cells in cancer immunotherapy - a short review.
AB  - Dendritic cells (DCs) are rare leukocytes that are uniquely potent in their
      recent application to therapeutic cancer vaccines. Isolated DCs loaded with
      tumour antigen ex vivo and administered as a cellular vaccine have been found to
      induce protective and therapeutic anti-tumour immunity. In the present report we
      describe the most common methods of culturing DCs and delivering tumour antigens
      and we summarise clinical trials of cancer immunotherapy using DCs-based
      vaccines.

PMID- 14655110
TI  - Preliminary immunohistochemical investigations of thyroid C cells in an
      experimental model of hyperthyroidism.
AB  - The role of the parafollicular (C) cells, the second most important cells in the
      thyroid gland, has not hitherto been clarified. They are considered to be
      disperse neuroendocrine cells of the APUD system and synthesise and release many
      of the regulatory peptides. Few publications are concerned with the evaluation of
      the structure and function of C cells in the thyroid gland or the probable
      relationship between these cells and the follicular cells in physiological and
      pathological conditions. For this reason immunohistochemical investigations were
      carried out into the activity of the C cells in rats in an experimental model of
      hyperthyroidism caused by chronic thyroxine influence. This C-cell activity was
      then evaluated. Differences in the quantity, distribution and calcitonin
      immunoreactivity of C cells were observed in hyperthyroid rats in comparison to
      the control group, together with a significant diminution of plasma TSH and
      calcitonin levels. Our preliminary study may indicate a functional interaction
      between follicular and parafollicular cells in the thyroid gland.

PMID- 14655111
TI  - The morphology and morphometry of the so-called "meningo-orbital foramen" in
      humans.
AB  - The so-called meningo-orbital foramen creates an additional link between the
      orbit and the cranial cavity. This bony canal, not always present in the human
      skull, contains a branch from the middle meningeal artery, providing an accessory
      blood supply to the orbit. This vessel, like the foramen, is characterised by
      great variability. Although older textbooks of basic anatomy suggested that it
      was a rare occurrence, some current data indicate a more frequent incidence of
      this foramen. These discrepancies were verified in our research. 92 orbits were
      studied on 46 macerated human skulls (25 male and 21 female). Although the
      incidence of the meningo-orbital foramen in the material as a whole was 28%, the
      foramen in female skulls was observed to be 40.5%, compared to 18% in male
      skulls. This difference was statistically significant. A double foramen was
      encountered in three orbits, and in one orbit there was a triple foramen. This
      means that in the material as a whole multiple foramina were observed in 4% of
      cases. Two measurements were taken to determine the localisation of the meningo-
      orbital foramen. The minimal distance between the supraorbital notch (or foramen)
      and the meningo-orbital foramen was 35.0 (28-44) mm. The minimal distance from
      the cross-point of the entrance to the orbit and the fronto-zygomatic suture was
      (21.3-35.5) mm. This indicates that the meningo-orbital foramen can lie near an
      operating field in some surgical interventions through the lateral orbital wall.

PMID- 14655112
TI  - Developmental pattern of calbindin D28k protein expression in the rat striatum
      and cerebral cortex.
AB  - We examined the protein expression of the calcium-binding protein calbindin D28k
      in two developing rat brain structures, the striatum and the cerebral cortex. The
      relative protein concentration level was quantified by means of the Western
      blotting method and densitometric scanning. 32 Wistar rats were used, divided
      according to survival period (P0-P120-postnatal days). Observations of the
      calbindin D28k protein expression in the rat striatum and the cerebral cortex
      revealed an increase in band color intensity between P0 and P10. The intensity of
      protein staining in older groups of animals stabilised at a similar level and in
      the P28 and P120 groups we observed a decrement of calbindin expression in the
      striatum. Calbindin D28k stabilises the intracellular calcium level, preventing
      calcium-induced apoptotic cell death in neurons. Thus, changes in calbindin D28k
      expression might be related to its neuroprotective role in differentiation and
      synaptogenesis during the postnatal development of the brain.

PMID- 14655113
TI  - A comparative study of the mammalian amygdala: a Golgi study of the basolateral
      amygdala.
AB  - The lateral (LA), basolateral (BL) and basomedial (BM) amygdaloid nuclei were
      compared in the guinea pig (Cavia porcellus), rabbit (Oryctolagus cuniculus) fox
      (Vulpes vulpes) and pig (Sus scrofa) by using the Golgi techniques. The
      interspecific comparisons of the individual basolateral nuclei have shown that
      the neuronal structure in each of them is extremely stable and remains almost
      unchanged in the series of animals studied. The only difference is the size of
      the basolateral neurons, which increases with the increasing size of the brain.
      Moreover, the intraspecific comparisons revealed that in all the animals studied
      LA, BL and BM form a fairly homogenous mass of cells in which similar cell types
      are present. The most numerous neurons in all basolateral nuclei are the spiny
      cells that often show a pyramidal or semi-pyramidal appearance (the Type I
      cells). Many of these have conical cell bodies and easily recognisable "apical"
      and "basal" dendrites. The Type II neurons are the most common variety of non
      pyramidal cell and have round cell bodies and smooth or sparsely spined
      dendrites. The axons of these cells often form a dense terminal field that
      remains in the vicinity of the parent soma. The Type III cells, which are only
      occasionally seen, are small spine-sparse neurogliaform neurons with a few
      extremely delicate beaded dendrites and a poorly branching local axon. These
      neurons were only located in LA and BL.

PMID- 14655114
TI  - The correlation of protein peroxidation with morphological changes in
      experimental oestradiol-induced carcinogenesis.
AB  - Oestradiol-induced male Syrian hamster carcinogenesis is a well-known
      experimental model of human cancer of the breast, ovary and uterus. The
      pathomechanism postulated in this model is 4-hydroxylation of oestradiol and
      further free radical formation. The same process is suspected in human breast
      cancer. Dynamic changes in protein peroxidation were reported during the tumour
      induction. In this paper we try to correlate the protein peroxidation markers
      with the histopathological progression of the changes. The biochemical and
      histopathological evaluations were performed after 1, 3, 6 and 9 months of the
      hormone exposition. Significant protein peroxidation was observed as soon as
      after 1 month and increased further until the 6th month. After 9 months however,
      it was not significantly different from the control. The discrete
      histopathological changes after 1 month, progressed into tubular and interstitial
      hyperplasias after 3 and 6 months. After 9 months several dysplastic areas,
      sometimes with features of carcinoma in situ, were observed. The severe 9-month
      histopathological changes did not correlate with the protein peroxidation.

PMID- 14655115
TI  - A magnetic resonance volumetric study of the temporal lobe structures in
      depression.
AB  - Depression is one of the most common psychiatric disorders and is associated with
      considerable morbidity. In recent years structural-imaging technology has
      provided an opportunity to examine the brain anatomy in patients with the
      psychiatric illness. 10 patients of various ages and, as the control group, 16
      healthy subjects were examined using the MRI method of neuroimaging. The volumes
      of the following structures were evaluated in the right and left hemispheres: the
      superior temporal gyrus, the basolateral temporal area (the region including
      middle temporal gyrus, inferior temporal gyrus and fusiform gyrus), the
      parahippocampal gyrus, the hippocampal head, the amygdaloid body and the lateral
      ventricle. The significant difference between the control group and the group
      with depression concerned the volume of the temporal horn of the lateral
      ventricle of both hemispheres. In depressed patients the left temporal horn was
      49.8% and the right 38.4% larger in comparison with the control group. In the
      control group there were significant differences between the left and right
      hemispheres in the volume of all the structures studied, whereas in the group
      with depression these difference in volume between the hemispheres concerned only
      the amygdaloid body and the lateral ventricle.

PMID- 14655116
TI  - Verification of selected anatomical landmarks used as reference points for
      universal goniometer positioning during elbow joint mobility range measurements.
AB  - The paper presents the results of comparative studies on the range of active
      elbow joint motion based on data obtained from 50 physical education students.
      The measurements were made with both an electrogoniometer and a manual
      goniometer. An explanation of differences in measurement results has been
      provided based on an investigation by the photographic method of 3 elbow joints
      using cadaveric material.

PMID- 14655117
TI  - Anatomical variants of the cervical vertebrae and the first thoracic vertebra in
      man.
AB  - Anatomical variants of the cervical part of the human spine were investigated.
      Morphological variants were studied on 100 cervical vertebrae (37 female and 63
      male). The greatest variability was demonstrated by the first cervical vertebra
      or atlas. The presence of some accessory bony arches embracing the vertebral
      artery was observed, namely the posterior bridge restraining the arcuate foramen
      (13.8%) and the lateral bridge restraining the transversovertical foramen (2%).
      Split posterior (3%) or anterior (1%) arches of the atlas were also encountered
      in this material. The superior articular face of the atlas divided into two parts
      was found in 47.8%. Variants of the remaining cervical vertebrae were limited
      only to the presence of a division of the transverse process foramina or their
      incomplete closure. Some of these anatomical variants may be a cause of certain
      clinical symptoms which have previously been described in the literature.

PMID- 14655118
TI  - A histological study of human ductus arteriosus during the last embryonic week.
AB  - It was found that the ductus arteriosus is a muscular channel and resembles the
      muscular artery in structure. The diameter of the ductus is equal throughout its
      length. At the orifice of the ductus to the aorta the cells of its wall blend
      with those of the aorta. The primordia of the tunica media of the aorta and the
      pulmonary trunk consist of regularly arranged, circular layers which are more
      evident than the layers forming the wall of the dutcus arteriosus.

PMID- 14655119
TI  - Analysis of the relationship between the inner structure and the magnitude of
      atherosclerotic plaques.
AB  - The aim of this study was ultrasound evaluation of atherosclerotic plaque
      morphology in relation to the degree of coronary artery lumen narrowing in
      patients with ischaemic heart disease. Intravascular ultrasound was performed on
      38 patients (30 men and 8 women) aged 35 to 77 (average age 60 +/- 11 years old)
      with symptoms of ischaemic heart disease. The structure of atherosclerotic
      plaques with a degree of lumen narrowing of < 50% (1st group) was distinctly
      different from the structure of plaques with a degree of lumen narrowing of 50
      75% (2nd group, p = 0.0045) and the structure of plaques with a degree of lumen
      narrowing of >/= 75% (3rd group, p < 0.001). The incidence of soft plaques
      decreased, whereas the percentage of mixed and hard plaques increased gradually
      with the increase in the degree of artery lumen narrowing. Significant
      differences in the incidence of plaque calcification were observed between the
      groups evaluated with crosssections of different degrees of lumen narrowing (p =
      0.0032). The smallest number of calcifications was discovered in the 1st group as
      compared to the 2nd (p = 0.0027) and the 3rd group (p = 0.0026). With a higher
      degree of lumen narrowing, a lower percentage of eccentric plaques and a higher
      percentage of concentric plaques were observed. There were more eccentric plaques
      and fewer concentric plaques in cross-sections of the 1 st group as compared to
      the 2nd group (p = 0.0056) and the 3rd group (p = 0.0018). A comparison between
      the 2nd and 3rd groups showed no significant difference in the incidence of
      eccentric or concentric plaques (p = 0.5). In conclusion, intravascular
      ultrasound evaluation revealed significant relationships between the structure,
      presence of calcifications and location of atherosclerotic plaques and the degree
      of artery lumen narrowing. The incidence of mixed, hard, calcified and concentric
      plaques increased, whereas the percentage of soft, non-calcified and eccentric
      plaques decreased gradually with the increase in the degree of artery lumen
      narrowing.

PMID- 14655120
TI  - Localisation of exogenous surfactants in cell membranes in the air-blood barrier:
      rat model.
AB  - The use of exogenous surfactants has been introduced into the therapy of patients
      of different ages. Much better results have been obtained in the treatment of
      respiratory distress syndrome with surfactants enriched with surfactant proteins.
      In the following study we used protein-containing surfactants (survanta and
      curosurf). The aim of the following study was to determine the localisation of
      artificial surfactants in the lung tissue. Using the Immunogold Technique,
      biotinylated surfactant proteins were traced in the air-blood barriers. In all
      lungs the exogenous surfactant was present only in some alveoli. In these parts
      small areas of atelectasis as well as oedema and transudate accumulation were
      seen. These changes were less severe after biotinylated curosurf treatment. In
      electron microscope studies we found surfactant elements in the air-blood barrier
      and other structures of the alveolar septa. Immunogold studies confirm the
      presence of biotynylated surfactant in the elements of the air-blood barrier.

PMID- 14655121
TI  - Digital analysis of the dynamics of the arterial supply to the human foetal
      kidneys.
AB  - Variations in the renal arteries in human individuals and foetuses have already
      been well studied. Contemporary trends in visualisation techniques focus on the
      evaluation of the dynamic parameters of blood flow in the vessels (speed,
      pulsatility, resistance). Most of these data have been obtained by the means of
      Doppler ultrasound (Fig. 1, 2). The authors have not found any anatomical
      database containing information about variability in the volume of the foetal
      renal arteries. The aim of the study is to design a database for variation in
      foetal renal artery volume in relation to foetal age and sex. The material
      consisted of digital images of the renal arteries filled with LBS-latex taken
      from 30 foetuses aged 12-19 Hbd. Digital analysis of the arteries was made with a
      unique form of software. The program is a 2D vector graphic editor using spliced
      functions of Bezier. Foetal age is estimated according to the last menstrual
      period and measurement of manual foot length and femur length (FL) as determined
      by ultrasound.

PMID- 14655122
TI  - Digital analysis of the volume of the human foetal suprarenal arteries.
AB  - Vascularisation of an organ is an index of its metabolic activity. The suprarenal
      glands are of crucial importance in the development of pregnancy. No data were
      found by the authors to describe the volume of the human foetal suprarenal
      arteries throughout pregnancy. The study was designed to form a database of human
      foetal suprarenal arterial volume in relation to foetal age and sex. Digital
      images were obtained at 4-week intervals of the suprarenal arteries of 30
      foetuses aged between 12-40 Hbd. The arteries were primarily filled with LBS
      latex. A unique form of software was designed to assist in incorporating vector
      graphics, spliced functions of Bezier, into the analysis. The arteries contoured
      by the geometric curves were calculated for their initial, average and terminal
      diameter, length and volume. The measurements were compared in relation to foetal
      age and sex at 4-week intervals. Foetal age was assessed by means of calculation
      from the last menstrual period, manual measurement of foot length and
      ultrasonagraphic measurement of femoral length. The suprarenal arteries in human
      foetuses are of strongly individual variation both in their origin and quantity.
      The volume of the arteries appears constant in the group analysed.

PMID- 14655123
TI  - The morphology, topography and cytoarchitectonics of the ciliary ganglion in the
      domestic turkey (Meleagris gallopavo domesticus).
AB  - The ciliary ganglion of the domestic turkey (Meleagris gallopavo domesticus) is
      located between the posterior wall of the eyeball and the optic nerve. It is
      closely connected with the oculomotor nerve; in particular with its inferior
      branch. The ganglion has a cask-like shape and is adjacent to the inferior branch
      of the oculomotor nerve. From this ganglion postganglionic fibres emerge which
      are arranged in two fasciculi. These are termed the long ciliary nerves and the
      short ciliary nerves. A cross-section of the ciliary ganglion revealed two
      populations of cells: small ones - choroid cells and large ones - ciliary cells.

PMID- 14655124
TI  - Changes in the bronchial epithelia in patients with immotile cilia syndromes.
AB  - Immotile cilia syndromes is a cause of recurrent infection of the airways and
      recurrent bronchopneumonias. Among the ciliary abnormalities are found changes in
      the structure of the microtubules, unco-ordinated ciliary movements caused by the
      absence of inner or outer or both dynein arms, and abnormalities of the
      kinetosomes and/or rete ridges. In patients with ciliary dyskinaesia bronchitis
      occurs early in life (during infancy) and usually has a recurrent tendency, so
      that bronchial biopsy is frequently undergone for diagnostic purposes. In this
      study we include 127 bronchial biopsies from patients (from 2 months to 49 years)
      unsuccessfully treated for recurrent respiratory tract infections. When
      performing regular diagnostic procedures on the light and electron microscopic
      level, we have looked for cilia abnormalities and also focused on changes within
      the mucosa and submucosa. The most common abnormality recorded was absence of the
      inner dynein arms, but in 40 cases neither of the dynein arms were present. Only
      a few patients had classical Kartagener's syndrome. Special attention is drawn to
      biopsies from elderly patients, in whom long-standing infections were followed by
      extensive damage to the bronchial epithelium, including even a total absence of
      ciliated cells. In some cases enhanced regenerative processes and some foci of
      squamous metaplasia were found. In two cases even foci of low-grade dysplasia
      were diagnosed.

PMID- 14655125
TI  - Evaluation of transfection effectiveness using fluorescein-labelled
      oligonucleotides and various liposomes.
AB  - Silencing of genes using siRNA represents a generally used technique aimed at
      inhibiting expression of proteins in cells. Results have frequently not met
      expectations and this has posed problems in association with this technique. The
      phenomenon might reflect an incorrect sequence of RNAi, poor penetration of the
      cells by the nucleotides or insufficient knowledge of the protein in question.
      The present study is aimed at evaluating the effectiveness of the transfection of
      selected cell lines using various liposomes. The studies were performed using 9
      cell lines: EPG 257/85 RNOV, EPG 257/85 RDB, W 181/A17, A 2780P, A 2780 RCIS,
      MEWO CIS, 181 RDB, 181 P and MCF-7/MX. The lines were transfected with
      fluorescently labelled oligonucleotides. Two parallel experiments were performed.
      In one oligofectamin and in the other DMRI were used as oligonucleotide carriers.
      The studies demonstrated that in every case nucleotides penetrated more than 90%
      of the cells. In 4 cell lines the signal was stronger when oligofectamin was
      used, in 4 cell lines when DMRI was employed and in one case the signal strength
      was comparable using any carrier. The studies showed that various liposomes
      demonstrated distinct transfection efficiency, depending on the cell line used,
      and that application of fluorescently labelled nucleotides may be helpful in the
      optimisation of transfection conditions.

PMID- 14655126
TI  - Preliminary assessment of anatomical variability of nervus peroneus superficialis
      in the foetal period.
AB  - An assessment of the variability of the course and ramifications of the
      superficial peroneal nerve within the crus was made on a material of 33 foetuses
      of both sexes miscarried in the 6th month of foetal life. Particular attention
      was paid to the relation of the nerve under examination to the anterior
      intermuscular septum. To facilitate the analysis the material investigated was
      grouped into several types. The post mortem examination revealed that the nerve
      referred to followed a typical course within the shank in 54% of cases. At the
      same time in 15% of cases the examined nerve was split into two terminal branches
      within the fascial compartment of fibular muscles, leaving the fascia
      independently. In 19% of cases n. peroneus superficialis passes through the
      intermuscular septum to the anterior fascial compartment of the shank. Moreover,
      in 12% of cases the presence was demonstrated of n. peroneus superficialis
      accessorius passing together with n. peroneus profundus to the extensors chamber
      and further on into the medial cutaneous nerve of the foot.

PMID- 14655127
TI  - Growth dynamics of the renal and suprarenal arteries in human foetuses.
AB  - The kidneys and suprarenal cortex are of common embryonic origin. The suprarenal
      gland and kidney have a common pathway in angiogenesis. Each of the organs is of
      key importance for intrauterine and individual development, yet they vary greatly
      in growth dynamics throughout pregnancy. The authors compared the arterial supply
      of these organs quantitatively in respect to foetal age and sex.

PMID- 14655128
TI  - Types of ethmoid sinus morphology on the basis of computed tomography
      examination.
AB  - The aim of the study was the application of computed tomography (CT) in the
      evaluation of types of ethmoid morphology. The material consisted of 197 CT
      examinations performed, using the Somatom AR.T (Siemens) CT scanner, in patients
      referred for CT for reasons other than sinus pathology. The examinations were
      performed in 2-mm contiguous axial scans. Ethmoid morphology was evaluated by
      means of classification into 3 types according to the degree of aeration and the
      relationship of the anterior ethmoid cells to the lacrimal sac on transversal
      scans. The most common was the II type (medium relationship to the lacrimal sac)
      found in 38.32% of the cases. Type III (large ethmoid sinus extending in front of
      the lacrimal sac) occurred in 32.49% of the patients, while the smallest sinus
      (Type I) was detected in the remaining 29.19% of the cases. In almost 1/5 of the
      cases asymmetry of the bilateral ethmoid anatomy was noted. It was concluded that
      CT examination was useful in the evaluation of ethmoid sinus morphology in
      respect to the lacrimal sac.

PMID- 14655129
TI  - Preliminary comparative immunocytochemical study of respiratory tract endocrine
      cells in certain rodents.
AB  - Studies were performed on 3 species belonging to two families: Microtidae (7
      common voles and 7 pine voles), and Muridae - 10 Wistar rats. In rodents the
      airways endocrine cells (ECs) are localised in the epithelium lining the larynx,
      trachea, bronchi, bronchioles and lung. CGRP-, synaptophysin (SY)-, calcitonin
      (CT)-, neuron-specific enolase (NSE)- and chromogranin A (CA)- immunoreactivity
      were nearly totally co-localised in ECs. In the region of the tracheo-larynx
      junction, CGRP- and NSE-positive cells were observed in the epithelium of the
      glands. It is surmised that some of the CGRP-positive ECs do not generate CT and
      CA, for the most part in ECs. In Microtidae ECs were more abundant than in the
      rat and were found even in the epithelium lining of the inside larynx in the
      transition region before the trachea.

PMID- 14655130
TI  - Digital-image analysis of the femoral shaft/neck angle in human foetuses.
AB  - Measurements were made of the femoral shaft/neck angle (CCD angle) in 106 human
      foetuses, aged from 16 to 38 hbd, using a "FEM-GEO_03" computer program. The
      values of the CCD angle in the group under examination were: mean = 140.48
      degrees, SD = 6.95 degrees, max = 157.90 degrees, min = 113.93 degrees. No
      significant differences were found in CCD angle size between male and female
      foetuses or between left and right bones. Dispersion analysis showed a decrease
      in the CCD angle during foetal development, which suggests that adaptation to a
      vertical position and bipedal gait starts during pregnancy and is manifest as an
      inborn feature.

PMID- 14655131
TI  - An immunohistochemical study of the thyroid parafollicular (C) cells in rats
      treated with cannabinoids - preliminary investigations.
AB  - The purpose of the present study was to evaluate the effect of a single
      intraperitoneal injection of a stable analogue of endogenous cannabinoid
      anandamide - R-(+)-methanandamide (2.5 mg/kg) and CP 55,940 (0.25 mg/kg), an
      egzogenous CB1 receptor-agonist, on the calcitonin (CT) immunoreactivity of the
      thyroid parafollicular (C) cells. Four hours after injection with both
      cannabinoids CT immunoreactivity, evaluated with an avidin-biotin peroxidase
      complex method by means of rabbit antibodies against CT, was seen to be enhanced
      in the parafollicular cells in comparison to those of the control group. In
      thyroids taken from cannabinoid-treated rats the majority of follicles,
      particularly those located peripherally were large in size, and had low
      epithelium. Moreover, dilatation of the blood vessels was observed. These changes
      were accompanied by a significant decrease in CT plasma level, without changes in
      calcium concentrations. This is the first evidence that a single injection of the
      cannabinoids R-(+)-methanandamide and CP 55,940 significantly decreases the
      activity of thyroid C cells.

PMID- 14655132
TI  - The morphological evaluation of the homograft wall in an electron microscopic
      study.
AB  - Cases of massive purulent infection of vascular prosthesis are demonstrated in
      this study. Infected prosthesis was substituted by arterial homograft, harvested
      during multi-organ procurement, and stored by the cold ischaemia method. In the
      follow-up period, the patients were divided into two groups, those treated with
      immunosuppression (n = 16) and those treated without immunosuppressive drugs (n =
      13). The patients underwent resurgery, during which a fragment of arterial wall
      was taken for electron microscopic examination. In the group with
      immunosuppression, the presence of the following structures was observed:
      endothelial cells, the intima, with a great number of elastic and collagen
      fibrils with fibrinogen inclusions, and active phagocyting myoblasts and
      myofibroblasts. In the group without immunosuppression electron microscopic
      examination showed the total destruction of the wall of the ruptured arterial
      homograft - absence of endothelium and sparse, damaged fibroblasts of the media
      or their degraded fragments, making a picture of cellular death. Morphological
      analysis of the arterial wall and the clinical state of the patient suggest the
      necessity of immunosuppressive treatment after fresh arterial homograft
      transplantation.

PMID- 14655133
TI  - Variability of the azygos vein system in human foetuses.
AB  - The aim of the study was to examine the variability of the azygos vein system and
      to determine the location of the veins with reference to the vertebral midline
      and the skeletopy of their termination. The research material consisted of 32
      human foetuses (14 male, 18 female) from 21(st) to 24(th) week of intrauterine
      life, fixed in 10% neutral formalin solution. Conventional anatomical -
      radiographic methods were used. 5 different configurations of the azygos vein
      system were found. In the 1(st) configuration there were 3 azygos veins, with
      both the left side veins, the hemiazygos vein (HV) and the hemiazygos accessory
      vein (HAV), joining the azygos vein (AV) separately. In the 2(nd) configuration
      the HV and the HAV were joined to the AV together. In the 3(rd )configuration the
      HAV was missing, and the 4(th) to 8(th) left intercostal veins were joined to the
      AV separately. In the 4(th) configuration the HV was missing. In the 5(th)
      configuration there was the AV only, which coursed along the vertebral midline.
      In these 4 configurations (1-4) the AV was located on the right side (90.6%) and
      in the 5(th) configuration the AV was located in the vertebral midline. The
      termination of the AV projected mostly on Th(4) (81.25%). The junction of the HV
      and the AV was found the most frequently at Th(8) (35.7%), and the junction of
      the HAV and AV most frequently at Th(4) (41.6%).

PMID- 14655134
TI  - Morphology of the extra-ocular muscles (musculi bulbi) of the American
      Staffordshire Terrier during the perinatal period.
AB  - The study was carried out on 12 American Staffordshire Terriers (AST) each of 60
      days' gestation. A morphological analysis of the extra-ocular muscles was
      performed. The location of the rectus and oblique muscles and the retractor bulbi
      muscle is described. The length and breadth of these muscles as well as of their
      tendons, the distance between the final insertions of the tendons and the corneal
      limbus and the line of insertions is also given.

PMID- 14655135
TI  - Bone marrow morphology during haematopoietic stem cell mobilisation with
      cyclophosphamide in mice.
AB  - The aim of the study was to examine the morphology of the bone marrow of mice
      after stimulation with cyclophosphamide (Cy). The experimental mice were given a
      single intraperitoneal injection with 250 mg/kg bw cyclophosphamide. After 2, 4
      and 6 days of experiment the femurs were obtained for morphological study. On the
      2nd day after the mobilisation of the mice with Cy destruction of the bone marrow
      was observed with a decrease in the haematopoietic compartment and an increase in
      the area occupied by sinusoids filled with erythrocytes. Erythrocytes were
      located among the haematopoietic cells, which indicated that the endothelial
      barrier had been disrupted. On the 4th day after treating the mice with Cy,
      repair processes in the bone marrow were conducted, including macrophages. The
      cells filled with haemosiderin migrated from the extravascular compartment of the
      bone marrow into the lumen of the sinusoids. There were proliferating cells among
      the haematopoietic cells. On the 6th day the morphology of the bone marrow was
      similar to the morphology of that in the control mice. However, more
      haematopoietic cells were visible compared to the control bone marrow. The
      presence of an increased number of leucocytes in the sinusoid lumen in comparison
      with the control suggested that at that time the migration of haematopoietic
      cells from the bone marrow had been initiated.

PMID- 14655136
TI  - Expression of connexin 43 in breast cancer in comparison with mammary dysplasia
      and the normal mammary gland.
AB  - Gap junctional intercellular communication (GJIC) plays a critical role in tissue
      development and differentiation and probably in carcinogenesis. The purpose of
      the study was to evaluate the expression and localisation of Cx43 in 40 cases of
      mammary dysplasia and 29 cases of breast cancer (without primary chemotherapy).
      The tissue sections were investigated for Cx43 expression by
      immunohistochemistry. In the normal mammary gland there was an intercellular,
      punctate staining pattern, mainly between myoepithelial cells, characteristic of
      functional gap junctions. In dysplasias there was mainly mixed (cytoplasmic and
      intercellular) staining and in most cases of breast cancer we observed diffuse or
      granular, but cytoplasmic, staining of Cx43. Our results demonstrated that
      expression of Cx43 in dysplasias and breast cancer is changed and GJIC is
      probably impaired because of disruption of functional gap junction formation
      especially between breast cancer cells.

PMID- 14655137
TI  - Activity of the thyroid parafollicular (C) cells in simple and hyperactive
      nodular goitre treated surgically - preliminary investigations.
AB  - The aim of this study was to evaluate the significance of measuring calcitonin
      (CT) plasma concentrations in patients with simple and hyperthyroid goitre
      treated surgically. Eighty four patients who underwent operations during the
      years 2000-2002 were analysed. Plasma concentrations of CT were determined by
      commercially available radioimmunoassay on the day of hospitalisation. Elevated
      concentrations of CT were found in 8 patients: in 5 out of 26 (19.2%) and in 3
      out of 33 (9.0%) patients with Graves' disease and with multinodular goitre,
      respectively. No major differences in concentrations of CT were observed in
      patients with simple goitre. Postoperative morphological analysis of
      pathologically changed hyperactive thyroids showed the presence of enlarged C
      cells distributed either in small groups or even singly with weakening
      immunohistochemical reaction for CT. These observations may point to the
      possibility of a relationship between the functional state of the thyroid gland
      and the activity of C cells.

PMID- 14655138
TI  - The descriptive traits of the thymus of twin fetuses.
AB  - The aim of the study is to establish formulae for the descriptive traits of
      twins' thymus. The formulae, apart from the fundamental types, also include
      numerous descriptive traits of the right and left part of the thymus and specify
      the nature of the joints of the parts. Devising the formulae for the thymus
      helped to compare pairs of twins of the same and of different sex.

PMID- 14655139
TI  - A quantitative analysis of the expression of alpha-smooth muscle actin in
      mesangioproliferative (GnMes) glomerulonephritis.
AB  - The aim of the study was to quantitatively assess the expression of alpha-SMA in
      the renal interstitium in GnMes cases. Two image analysis approaches (in grey
      scale and in spatial colour images) were used to determine correctly the presence
      of the reaction. In spatial evaluation, the mean area fraction of a-SMA in the
      renal interstitium was 3.63% +/- 1.29%, while the results obtained from
      traditional quantitative method based on grey scale images were biased and too
      low.

PMID- 14655140
TI  - The influence of experimental Bacteroides fragilis infection on substance P and
      somatostatin-immunoreactive neural elements in the porcine ascending colon - a
      preliminary report.
AB  - The present study was aimed at disclosing the influence of Bacteroides fragilis
      (one of the most important bacterial agents causing colitis in children)
      experimental infection on the expression of substance P (SP) and somatostatin
      (SOM) in neurons and nerve fibres within the porcine ascending colon. Distinct
      differences in the distribution pattern of neural elements immunoreactive to the
      substances studied were observed between the experimental (Inflam) and control
      (Contr) pigs. In general, the number of SP-IR neurons and nerve terminals
      increased, while the expression of SOM decreased after Bacteroides fragilis
      induced colitis (BFIC). However, distinct differences in the intensity of these
      alterations were observed between particular compartments of the bowel segment
      studied. Thus, the present results suggest that SP- and SOM-immunoreactive (SOM
      IR) elements of the enteric nervous system play a part in the control of colonic
      activity during BFIC.

PMID- 14655141
TI  - The range of motion of the cervical spine in children aged from 3 to 7 years - an
      electrogoniometric study.
AB  - The aim of the study has been to evaluate the range of motion of the cervical
      spine in relation to the age of the participants, and to determine the dimorphic
      and asymmetrical differences in the range of motion in pre-determined age
      categories. The study involved 300 children (150 girls and 150 boys) aged from 3
      to 7 years, and tensiometric electrogoniometry was used to evaluate the range of
      cervical spine motion. The highest amplitude of cervical spine motion could be
      observed in the transverse plane and this was followed by that of the sagittal
      plane, with frontal plane motion being the lowest. The dynamics of the cervical
      spine motion changes were characterised by the presence of two distinct periods
      of motion increase - between years 2 and 3 and between years 6 and 7; the other
      periods were characterised by a decrease in cervical spine motion. The dimorphic
      and asymmetrical differences proved statistically insignificant.

PMID- 14655142
TI  - The effect of calcitriol and its analogues on proliferation and hormone
      expression in cultured cells of thyroid medullary carcinomas.
AB  - The study aimed at evaluating the effects of calcitriol and of its analogues on
      the proliferation of TT and rMTC cells (human and rat line tumour cells
      originating from thyroid medullary carcinoma) and at examining the effects of the
      substances on the secretion of the principal hormones of the cells, calcitonin
      (CT) and calcitonin gene-related peptide (CGRP). Cells of thyroid medullary
      carcinoma (human TT cells and rat rMTC cells) were cultured for 5 days in the
      absence or in the presence of calcitriol and of its two analogues (PRI-1906 and
      PRI-2191) in concentrations of 10(-9) to 10(-6) M. Calcitriol and the applied
      analogues weakly inhibited proliferation of thyroid medullary carcinoma in in
      vitro conditions. The evident effect of analogues on hormone secretion points to
      their effect on the process of CT gene expression.

PMID- 14655144
TI  - A comparison of the anatomical structure of odontoblasts and the connective
      tissue fibres in relation to the age of the patient.
AB  - The aim of this work was to study the structure of dental pulp (mainly the
      connective tissue fibre and odontoblasts) during the active production of dentine
      in relation to the age of the patient. The pulps of the teeth extracted for
      orthodontic reasons from a population of 10-50 year-olds were investigated with
      the help of a transmission electron microscope (TEM) and a scanning electron
      microscope (SEM). Condensation of the small collagen fibres and fibrils around
      the morphotic elements of the dental pulp were found more often in the elderly
      patients.

PMID- 14655143
TI  - Localisation of oestrogen receptors (ERalpha and ERbeta) in the human and rat
      epididymides.
AB  - The aim of the study was to compare the localisation of oestrogen receptors alpha
      and beta (ER alpha and ER beta) in the human and rat epididymides. In the human
      epididymis the immunoexpression for ER alpha was detected in the nuclei of the
      caput epithelial cells, while positive reaction for ER alpha was observed in the
      nuclei of the cauda epithelial cells. In the rat epididymis, immunoexpression for
      ER alpha showed nuclei of the caput and cauda epithelial cells. However, the
      reaction was stronger in cells of the caput epididymis. A positive reaction for
      ER beta was observed in the nuclei of smooth muscle cells of the epididymal duct
      and in the nuclei of interstitial tissue cells of the rat caput and cauda
      epididymis. We have demonstrated that localisation of ER alpha and ER beta is
      cell-, region- and species-dependent.

PMID- 14655145
TI  - PCNA and laminin as prognostic factors in primary Fallopian tube carcinoma.
AB  - Primary Fallopian tube carcinoma (PFTC) is one of the rarest malignant tumours of
      the female genital tract. Staging of the disease according to FIGO scale is the
      most common prognostic indicator. Others, such as histological type, grading
      according to Hu classification, depth of tubal wall invasion, the presence of
      neoplastic cells in peritoneal leakage, invasion of the lymphatic and blood
      vessels, mitotic activity, DNA ploidy, Ki-67 expression, AgNOR level and p53 and
      c-erbB-2 immunoreactivity, are not widely accepted. 70 cases of primary Fallopian
      tube carcinomas were analysed with regard to clinicopathological data, survival
      and the expression of proliferating cell nuclear antigen (PCNA) and laminin.
      Histological classification of PTFC revealed 26 cases of the endometriod type, 16
      undifferentiated, 15 serous, 8 urothelial, 3 clearcell and 3 of other types. A
      total of 70 cases revealed positive nuclear staining for PCNA. The index of PCNA
      (labelling index, LI, proportion of PCNA-positive cells relative to all
      neoplastic cells) was evaluated. PCNA LI values were classified as high, > 0.45,
      or low, </= 0.45. Intracellular expression of laminin was found in 46 cases and
      extracellular in 28 cases. There was no significant correlation between the
      expression and distribution of laminin and survival. The p value was
      statistically significant only for PCNA LI as an independent prognostic factor.

PMID- 14655146
TI  - Morphological and functional evaluation of spermatozoa from patients with
      asthenoteratozoospermia.
AB  - In several cases of asthenoteratozoospermia, electron microscopic investigation
      displayed immature sperm forms, morphological apoptotic patterns of spermatozoa
      and many cytoplasmic conglomerates with fragments of the sperm. In these
      patients, TUNEL assay showed a high percentage of spermatozoa with nuclear DNA
      fragmentation. Moreover, thickened and deformed midpieces were observed which
      contained supernumerary and redundant mitochondria with normal oxidoreductive
      capability and normal membrane potential. In these cases a high percentage of
      spermatozoa with normal DeltaPsim was detected. Nevertheless, a subpopulation of
      patients was found with an abnormal ultrastructure of sperm mitochondria and with
      a low percentage of spermatozoa with normal DeltaPsim. These findings indicate
      that low motility of spermatozoa may be related to abnormal morphogenesis of the
      midpiece containing functional mitochondria and that this may be a possible
      consequence of an apoptotic mechanism. Furthermore, our results show that
      asthenoteratozoospermia may result from dysfunction of sperm mitochondria and/or
      with alternations of the structures involved in sperm motility, i.e. the dense
      outer fibres, the fibrous sheath and the axoneme.

PMID- 14655147
TI  - Tissue expression of cytokines (IL-1alpha, IL-2, IL-6, IL-12, TNF-alpha) in B
      cell lymphomas in children.
AB  - In most malignant tumours disturbed production of cytokines and of their
      receptors can be noted. The main immune system cells engaged in tumour regression
      with the involvement of cytokines include helper lymphocytes (Th1), cytotoxic
      lymphocytes (Tc) and dendritic cells. It has been noted that cytokines are also
      produced by the cells of a tumour. The present study aimed at immunocytochemical
      localisation of cytokines (IL-1alpha, IL-2, IL-6, IL-12, TNF-alpha) in B-cell
      lymphomas in children (n = 10). The studies were performed on surgical material
      following formalin fixation and embedding in paraffin. The control material
      involved human reactive lymph nodes (n = 5). IL-2, IL-6, IL-12 were detected in
      4/10 examined cases. Expression of IL-1alpha was highly pronounced, as in the
      control, and was detected in 6/9 examined patients. No TNF-alpha could be
      demonstrated in tumours even if lymph node expression of the cytokine was
      demonstrated in the control. The studies pointed to a decreased production of
      antitumour cytokines in B-cell lymphomas in children, which might correspond to
      the progression of the tumour.

PMID- 14655148
TI  - The expression of calcitonin, calcitonin gene-related peptide and somatostatin in
      the thyroids of rats of different ages.
AB  - Using immunocytochemistry and in situ hybridisation expression of calcitonin,
      calcitonin gene-related peptide (CGRP) and somatostatin was examined in rat
      thyroids. The immunocytochemical reactions demonstrated the presence of the
      proteins under investigation at all stages of rat life. Calcitonin and CGRP
      produced the most numerous parafollicular cells, while somatostatin was present
      in a few cells only. The number of cells producing the above-mentioned hormones
      was found to increase in rats with the progressing of age. Hybridocytochemical
      techniques corroborated the results obtained using immunocytochemical techniques.
      The most numerous cells were found to contain mRNAs for calcitonin and CGRP. In
      the case of somatostatin, however, multiple parafollicular cells produced mRNA
      for the hormone but few cells demonstrated the presence of the corresponding
      protein.

PMID- 14655149
TI  - Effect of hCG on the morphology of rat epididymal epithelial cells in vitro.
AB  - The epididymis is an androgen-dependent organ. The hormones regulate the
      morphology and secretory activity of the epididymal epithelial cells. The cells
      in vitro resume their function as in vivo and also reveal features of
      steroidogenic cells. It can be expected that, as with Leydig cells, the
      morphology and function of the cells can be regulated by LH/hCG. The aim of the
      study was to assess the morphology of epididymal epithelial cells in vitro after
      stimulation with hCG. The experiment was performed on cells isolated from
      sexually mature rats. The epididymal epithelial cells were cultured in a medium
      with the addition of dihydrotestosterone (DHT). Moreover, the cells were cultured
      in the medium with DHT and without DHT but enriched with hCG. The epididymal
      epithelial cells cultured with DHT formed a monolayer and accumulated glycogen, a
      PAS-positive substance and lipid droplets. The cells cultured without DHT were
      stellate in shape and low in glycogen and PASpositive substance but they
      contained lipid droplets. The morphology of epididymal epithelial cells cultured
      without DHT but after stimulation with hCG was similar to the morphology of the
      cells cultured with DHT. This was the first sign that the morphology of the cells
      can be influenced by hCG.

PMID- 14655150
TI  - The expression of metallothionein (MT) and proliferation intensity in ovarian
      cancers treated with cisplatin and paclitaxel.
AB  - Metallothioneins (MT) represent low molecular weight proteins that are supposed
      to fulfil several functions. They participate in the cell cycle, protect cells
      from oxidative stress, control levels of heavy metals and participate in
      multidrug resistance processes, particularly in cases of alkylating drugs. The
      present study aimed at evaluation of proliferation intensity (Ki67, PCNA) in
      ovarian cancers treated using cisplatin and paclitaxel, as related to expression
      of MT. The experiments were performed on samples originating from 10 patients
      operated on due to ovarian cancer. The material originated from the first
      operations or second-look operations. All the patients were treated with
      cisplatin and paclitaxel. Immunocytochemical reactions using antibodies to MT,
      Ki67 and PCNA were performed in paraffin sections originating from the cases
      studied. Statistical analysis was performed using Statistica software. The
      studies demonstrated no relation between expression of MT on the one hand and
      intensity of proliferation before or after chemotherapy on the other hand (gamma
      correlation, p > 0.05). The results indicate that expression of MT is not related
      to resistance to treatment using cisplatin and paclitaxel.

PMID- 14655151
TI  - The expression of selected neuroendocrine markers and of anti-neoplastic
      cytokines (IL-2 and IL-12) in lung cancers.
AB  - We have continued our studies by detecting three markers of neuroendocrine
      tumours of the lungs, including chromogranin A, NSE and synaptophysin, to confirm
      the neuroendocrine origin of lung tumours and by examining the content of two
      anti-neoplastic cytokines, IL-2 and IL-12 in the tumours. The studies were
      performed on paraffin sections of lung carcinoids (n = 13) and small cell lung
      carcinomas (SCLC) (n = 15). Pronounced expression of all 3 markers of
      neuroendocrine tumours was detected in most of the pulmonary carcinoids and in
      5/15 of SCLC. Co-expression of the two cytokines (IL-2 and IL-12) in tumour cells
      was detected in 12/13 patients with lung carcinoid and expression of at least one
      cytokine in 12/15 patients with SCLC. Significantly lower numbers of cells
      immunoreactive to both cytokines were detected in SCLC as compared to lung
      carcinoids. The studies have confirmed the literature data on the lowered
      secretion of IL-2 in SCLC and extend the data by supplying information on the
      expression of IL-12. The lowered expression of the two cytokines at the time of
      diagnosis may represent a prognostic factor for survival in SCLC.

PMID- 14655152
TI  - The expression of androgen receptors in the epithelial cells of the rat prostate
      lateral lobe in experimental hyperprolactinaemia: a morphological and
      immunohistochemical study.
AB  - The effect of hyperprolactinaemia on the prostate has still not been fully
      elucidated. The aim of the study was to estimate the influence of
      hyperprolactinaemia on expression of the androgen receptor (AR) in rat epithelial
      cells of the prostate lateral lobe and on the morphology of these cells. Studies
      were performed on sexually mature male Wistar rats. To provoke
      hyperprolactinaemia rats received i.p. metoclopramid (MCP). For light and
      electron microscopy the lateral lobes were obtained routinely. The intensity of
      the immunohistochemical reaction of AR (expression of AR) in the epithelial cells
      of the prostate lateral lobe was assessed by optical density measurements with
      the help of computer image analysis. Ultrastructural observations of the
      epithelial cells of the lateral lobe were carried out by means of transmission
      and scanning electron microscopes. The results showed a more than twofold
      increase in prolactin (PRL) concentration in the serum, but a twofold decrease in
      testosterone (T). The intensity of the immunohistochemical reaction of AR in the
      epithelial cells of the lateral lobe in the experimental group was higher than in
      the control group. We noted changes in the morphology of the epithelial cells of
      the prostate lateral lobe in the experimental group.

PMID- 14655153
TI  - Ovarian morphology and hormonal profiles in gilts following surgical denervation
      at day 12 of the oestrous cycle - preliminary data.
AB  - To establish the role of the nervous system in the etiopathogenesis of ovarian
      cysts we studied ovarian morphology and hormonal profiles in gilts that had
      undergone bilateral surgical denervation at day 12 of the oestrous cycle. Blood
      samples were collected from day 13 of the first cycle until day 20 of the second
      studied cycle. On this day the number of follicles (6 to 10 mm in diameter) was
      lower (p < 0.01) in the denervated ovaries when compared to the control group.
      Denervation resulted in a dramatic reduction in the number of TH/D betaH- and/or
      NPY-IR nerve fibres, especially in the vicinity of the follicles. Furthermore,
      denervation lead to a decrease (p < 0.05-0.001) in plasma concentrations of P(4)
      (at day 15 and 16 of the first cycle and during the luteal phase of the second
      studied cycle) and LH and E(2) (mainly during the perioestrous period). These
      results suggest that sympathetic neurons supplying ovaries may participate in the
      follicular development and steroidogenesis in gilts.

PMID- 14655154
TI  - Relations between Leu(5)-enkephalin- (LENK) and VIP-immunoreactive nerve fibres
      during human drug-resistant colitis. A case study.
AB  - The double immunofluorescence technique was used to examine the distribution and
      interrelationship between LENK- and VIP-immunoreactive nerve fibres within the
      muscle layer and myenteric plexus of the large intestine in a young female
      patient (aged 17 years) suffering from colitis ulcerosa activa (CUA). As the CUA
      was found to be totally drug-resistant, a pancolotomy was performed by means of
      the Soave technique. Varicose nerve fibres, immunoreactive either to LENK or VIP,
      but not to both substances simultaneously, were found in all fragments of the
      bowel studied. A striking feature was their distribution pattern within the
      studied layers. In all cases LENK-IR fibres were closely accompanied by VIP-IR
      terminals. The density of the examined fibres depended on the bowel fragment
      studied, and was the greatest in the sigmoid colon, descending colon and rectum,
      while the lowest number was found in the caecum. The results of the present study
      may thus be indicative for the involvement of LENK- and VIPIR nerve fibres in the
      control of bowel functions during CUA, possibly on the basis of a "cross-talk"
      between terminals running in close vicinity to each other.

PMID- 14655155
TI  - The expression of selected immunocytochemical diagnostic markers in the case of
      chondrosarcoma with a mesenchymal component.
AB  - The case of 52-year-old man is presented, who had suffered from pains in his
      right brachial region and in whom, upon admission to the Lower Silesia Centre of
      Oncology, a tumour of 20 cm in diameter and restricted mobility was disclosed in
      the right brachial region and proximal 1/3 of his right arm. Radiograms of his
      right humerus disclosed non-uniform restructuring of the osseous tissue,
      dominated by osteosclerosis in the upper half of his right humerus, while in the
      surrounding dift tissues of the proximal portion non-uniform shades were seen of
      calcified appearance. The patient was qualified to surgical biopsy and
      histopathological examination of the sample disclosed Chondrosarcoma G II.
      Following amputation of the right upper extremity together with the scapula, the
      tumour was subjected to histopathological and immunocytochemical examination in
      the Department of Pathomorphology, Lower Silesia Centre of Oncology. In numerous
      samples of the tumour dedifferentiated chondrosarcoma was diagnosed with a
      dominating component of malignant fibrous histiocytoma (MFH), which was confirmed
      by detecting a high expression of alpha-1-antichymotrypsin (ACT) within the
      spindle-shaped cell component of the chondrosarcoma. Spindle-shaped elements in
      dedifferentiated chondrosarcoma (DChSa) may represent patterns of fibrosarcoma,
      osteosarcoma or the malignant fibrohistiocytoma (MFH) type and they are present
      as if in the form of restricted fields with no reciprocal infiltrates. Moreover,
      due to the worse prognosis in the case of the MFH component in dedifferentiated
      chondrosarcoman as compared to that in classical chondrosarcoma, common
      evaluation of the material was made by a surgeon, radiologist and
      histopathologist, accompanied by a minimum panel of immunocytochemical tests
      (ACT, Vimentyna, Desmina, S-100). This enabled a final diagnosis for all tumour
      components to be established and prognosis to be made regarding the further fate
      of the patient.

PMID- 14655156
TI  - A developmental anomaly of the mammary glands - gigantomastia. A case report.
AB  - Developmental anomalies of the breast are frequently observed in women. The most
      serious pathology is gigantomastia. This type of breast hypertrophy may be caused
      by hypersensitivity of the breast oestrogen and progesterone receptors, by
      disturbances of the normal balance of oestrogen and androgen hormones, by
      hyperthyroidism or by hormonal activity of the neoplasm. In most cases
      gigantomastia produces pathological changes in the vertebral column which become
      manifest as discopathia, scoliosis or scoliokyphosis. A case of gigantomastia
      treated with surgery is presented and the effect of plastic operation is
      demonstrated. Surgery may be recommended as an excellent therapeutic treatment of
      gigantomastia.

PMID- 14655157
TI  - Mammary gland anatomy and the role of mammography and ultrasonography in the
      early diagnostics of breast cancer. A case report.
AB  - Progress in imaging techniques has brought a solution to the problem of the early
      diagnosis of breast cancer. An interesting case of breast cancer is presented
      here, pictures of the malignant tumour are demonstrated and the usefulness of new
      diagnostic methods analysed. The presentation of this case may contribute to
      greater effectiveness in early breast cancer detection.

PMID- 14655158
TI  - Axillary lymph node and early breast cancer diagnostics. A case report.
AB  - Understanding of the anatomy of the axillary lymph nodes is important in
      diagnostic and treatment procedures for breast cancer. An interesting case is
      presented here of breast cancer without a breast tumour. The first symptom of the
      disease was lymphadenopathy of the axillary region. This kind of case is
      extremely rare in clinical practise (one case per 1-5 years) and constitutes a
      great problem for specialists, since in many cases the primary neoplasm source is
      unknown. The anatomical and clinical implications of such a situation are
      discussed.

PMID- 14655160
TI  - Investigation in vomiting children.
AB  - This article discusses how to investigate various surgical causes of vomiting.
      Particular emphasis is placed on plain radiographic, ultrasound, and contrast
      study findings. The article touches upon nineteen different diseases, and
      encompasses diseases found in neonates to adolescents.

PMID- 14655161
TI  - Malrotation and volvulus in infancy and childhood.
AB  - The subject of malrotation and midgut volvulus in infancy and childhood is
      reviewed from the perspective of experience with 138 patients evaluated in a
      published series and a further 82 cases seen since. Embryology, historical
      aspects, clinical presentation, investigation, surgery, and outcome are
      discussed. The diagnosis of malrotation and volvulus should always be kept in
      mind when assessing any infant or child with symptoms of vomiting and pain,
      particularly when the vomiting is bile-stained. The diagnosis cannot be excluded
      if diarrhea is present, when clinical findings are bland, or even with normal
      abdominal radiographs. A contrast meal and follow-through should be done and, if
      correctly interpreted, should be diagnostic. Ultrasound examination may be
      helpful but is not secure enough to exclude the diagnosis. Laparotomy or
      laparoscopy is the only way to be sure. Malrotation with its propensity for
      volvulus is truly a time bomb lying within.

PMID- 14655162
TI  - Gastroesophageal reflux.
AB  - Gastroesophageal reflux is common in infants and generally resolves spontaneously
      within the first year of life as the lower esophageal sphincter mechanism
      matures. The reflux is only considered a "disease" (GERD) when it becomes
      symptomatic or causes pathological consequences. GERD is commonly associated with
      esophageal atresia and there is a high incidence in neurologically impaired
      children; in both groups conservative treatment is notoriously ineffective. The
      diagnosis of GER is made on upper gastrointestinal contrast studies, endoscopy
      and pH monitoring. Medical management comprises antacids, reduction of gastric
      acid production and prokinetic agents. The indications for antireflux surgery
      include an established esophageal stricture, associated anatomical defect and
      failure of medical therapy. Apnoeic episodes secondary to documented GER in the
      infant, constitute an absolute indication for early surgery.

PMID- 14655163
TI  - Intestinal obstruction in neonatal/pediatric surgery.
AB  - Intestinal obstruction in the newborn infant and older child may be due to a
      variety of conditions, including atresia and stenosis, annular pancreas,
      malrotation, duplication cyst, meconium ileus, meconium plug syndrome and
      neonatal small left colon syndrome, Hirschsprung's disease, neoplasia, trauma,
      and other rarer causes. The mode of presentation can be acute or more chronic
      with systemic upset due to shock. Neonates, more so than older children, with
      unrecognized intestinal obstruction deteriorate rapidly, show an increase of
      associated morbidity and mortality and appropriate surgical treatment becomes
      more hazardous. Early diagnosis depends largely on the prompt detection of
      obstructive manifestations by the clinician and the subsequent accurate
      interpretation of radiographic findings and other investigations, leading to
      definitive treatment, which should always be preceded by appropriate
      resuscitation/preparation of the infant/child. Management of intestinal
      obstruction will almost always be surgical, apart from some notable exceptions
      and all are discussed in more detail. With the advent of pediatric and neonatal
      intensive care and multidisciplinary care, the morbidity and mortality of cases
      of intestinal obstruction reported in current series is generally extremely low
      and mainly determined by the coexistence of other major congenital anomalies (eg,
      cardiac), delays in diagnosis and treatment or coexisting medical conditions.
      Newer treatments and future developments may reduce the residual mortality in
      such cases as ultrashort-bowel syndrome.

PMID- 14655164
TI  - Abdominal migraine and cyclical vomiting.
AB  - Vomiting and abdominal pain are symptoms that may arise from a number of
      different causes. Cyclical vomiting and abdominal migraine are terms that have
      been applied to a presentation characterized by its episodic pattern and
      intervals of complete health. The 2 share many clinical features, but it is
      important to distinguish them as they have different responses to therapies such
      as prophylactic antimigraine medications. Both are noted for the absence of
      pathognomonic clinical features but also for the large number of other conditions
      to be considered in their differential diagnoses. Definitive diagnosis is
      frequently delayed. It is important to carefully evaluate these patients as well
      being between vomiting episodes does not guarantee the absence of organic
      disease. While there is a role for a basic set of diagnostic tests, there is
      evidence to suggest that a trial of empiric therapy with upper gastrointestinal
      and small-bowel radiological studies is cost-effective.

PMID- 14655165
TI  - Intestinal neuronal dysplasia.
AB  - Intestinal neuronal dysplasia (IND) is a clinical condition that resembles
      Hirschsprung's disease. In the past many years investigators have raised doubts
      about the existence of IND as a distinct histopathologic entity. One strong piece
      of evidence that IND is a real entity stems from animal models. Recently, two
      different HOX11L1 knockout mouse models and a heterozygous endothelin B receptor
      deficient rat demonstrated abnormalities of the submucous plexus similar to that
      observed in human IND. This review describes in detail the diagnostic criteria of
      IND, staining techniques, correlation between histological findings and clinical
      symptoms, and management of IND.

PMID- 14655166
TI  - Infection and the gut.
AB  - Gastrointestinal symptoms, including vomiting, are caused by a variety of
      infective organisms in children, many of which are self-limiting and resolve
      within a week, but others are potentially much more serious in their
      consequences. Diarrhea, vomiting and abdominal pain are common but nonspecific
      symptoms. Investigation is dictated by the likely causative organism, given the
      age and presentation of the child. The role of bacteria in the pathogenesis of
      necrotizing enterocolitis, recognition that Yersinia, Campylobacter and
      Salmonella may produce symptoms difficult to distinguish clinically from
      appendicitis, the viral causes of idiopathic intussusception, the occurrence of
      intussusception after administration of rotavirus vaccine, and the evidence
      incriminating mycobacterium avium subspecies paratuberculosis in the aetiology of
      Crohn disease are discussed.

PMID- 14655167
TI  - The embryology of gut rotation.
AB  - Until today, the puzzling spectrum of midgut "malrotations" is commonly explained
      by an "impaired" process of rotation of the midgut. However, a closer look at the
      literature reveals that the description of this "process of rotation" is rather
      schematic and is aimed more at explaining pathological findings, while detailed
      proper embryological investigations are still rare. Despite recent trials, good
      animals models that would allow the comparison of normal and abnormal midgut
      development are still missing. In the first part of this article, the "normal
      process of rotation," as it is described in the literature, is presented and
      critically analyzed. In general, it is a shortcoming that reliable illustrations
      of these crucial embryological processes are missing in most of these papers.
      Therefore, in the second part of this review scanning electron microscopy
      pictures of the developing midgut are presented in a series of rat embryos. In
      these pictures clear signs of a process of rotation are missing.

PMID- 14655174
TI  - USRDS: the United States Renal Data System.

PMID- 14655179
TI  - Excerpts from the United States Renal Data System 2003 Annual Data Report: atlas
      of end-stage renal disease in the United States.

PMID- 14655180
TI  - Is there really an increase in non-minimal change nephrotic syndrome in children?
AB  - BACKGROUND: Reports on the worldwide increase in focal segmental
      glomerulosclerosis (FSGS) in childhood may have been hampered by referral bias. A
      true increase in FSGS possibly could alter the current practice of withholding
      renal biopsy in childhood nephrotic syndrome (NS) unless the patient fails to
      respond to a 28-day course of corticosteroid therapy. METHODS: With these
      questions in mind, we analyzed a 17-year database covering a 275,000-child
      population with mandatory referral. The incidence of NS per 100,000 childhood
      population per year was calculated, charts of 159 patients with NS seen between
      1985 and 2002 were reviewed, and a receiver operating characteristic (ROC) plot
      analysis was performed to analyze the diagnostic performance of remission time.
      RESULTS: Results show that 115 of 159 patients had minimal change NS, diagnosed
      either on the basis of corticosteroid response (n = 89), verified by renal biopsy
      (n = 14), or with minimal change plus mesangial immunoglobulin M on histological
      examination (n = 12). The remaining 44 patients underwent a renal biopsy showing
      FSGS (n = 29; 18.2%), diffuse mesangial hypercellularity (n = 8; 5%),
      membranoproliferative glomerulonephritis (n = 1; 0.6%), membranous nephropathy (n
      = 3; 1.9%), or other diagnoses (n = 3). The incidence of FSGS increased
      significantly (P = 0.0253) from 0.37 to 0.94/100,000-child population/y in the
      two 8(1/2)-year intervals of our study. ROC plot analysis confirmed diagnostic
      sensitivity and specificity greater than 80% for remission time between 21 and 28
      days of therapy. CONCLUSION: We confirm the increasing incidence of FSGS in
      children with idiopathic NS in a well-defined catchment area and, at the same
      time, find no reason to change the initial therapy and current indications to
      perform renal biopsy in childhood NS.

PMID- 14655181
TI  - Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent
      nephrotic syndrome.
AB  - BACKGROUND: A proportion of patients with steroid-dependent nephrotic syndrome
      (SDNS) experience frequent relapses despite long-term treatment with steroids,
      levamisole, or/and cyclophosphamide. We prospectively examined the efficacy of
      long-term therapy with mycophenolate mofetil (MMF) as a steroid-sparing agent in
      this group. METHODS: Nineteen patients with a mean age of 99.1 months (95%
      confidence interval [CI], 85.3 to 113) who had previously undergone long-term
      therapy with prednisolone (n = 19), levamisole (n = 16), and cyclophosphamide (n
      = 15), but had continued to show steroid dependence over many years, were
      studied. Renal biopsy showed minimal change disease and focal segmental
      glomerulosclerosis in 10 and 3 patients, respectively. Patients were administered
      MMF at a mean dose of 29 mg/kg/d (95% CI, 27.4 to 30.7) in 2 divided doses and
      decreasing doses of alternate-day prednisolone for a mean of 11.8 months (95% CI,
      11.4 to 12.2). Relapses were treated with daily prednisolone until remission,
      with tapering later. They were additionally followed up for a mean of 17 months
      (95% CI, 15.9 to 18.1). RESULTS: Mean relapse rates decreased from 6.6 (95% CI,
      5.4 to 7.7) to 2 episodes/y (95% CI, 1.2 to 2.7) during MMF treatment (P <
      0.0001). Four patients each had 0, 1, 2, and 3 relapses; failure of MMF therapy
      (>3 relapses during treatment) was seen in 3 patients. Treatment with MMF
      resulted in steroid sparing, with a reduction in mean prednisolone dose from 0.7
      (95% CI, 0.6 to 0.8) to 0.3 mg/kg/d (95% CI, 0.2 to 0.4; P < 0.0001). Fourteen
      patients showed a 50% or greater reduction in relapse rates; prednisolone therapy
      could be discontinued for 6 or more months in 8 patients. No significant
      gastrointestinal or hematologic side effects of MMF treatment were noted. After
      discontinuation of MMF treatment, 68.4% of patients had an increased frequency of
      relapses and recurrence of steroid dependence, requiring treatment with other
      medications. CONCLUSION: Long-term therapy with MMF results in significant
      steroid sparing and reduction in relapse rates in patients with SDNS. Therapy
      with MMF and tapering doses of prednisolone appears to be a promising
      intervention in children with SDNS.

PMID- 14655182
TI  - A combined low-density lipoprotein apheresis and prednisone therapy for steroid
      resistant primary focal segmental glomerulosclerosis in children.
AB  - BACKGROUND: Treatment of steroid-resistant (SR) primary focal segmental
      glomerulosclerosis (FSGS) remains a major challenge in nephrology. A prospective
      study was conducted to clarify the therapeutic role of low-density lipoprotein
      apheresis (LDL-A) in 11 nephrotic children with SR and cyclosporine A (CsA)
      resistant primary FSGS. METHODS: Based on entry criteria, all 11 eligible
      patients had biopsy-proven primary FSGS presenting with nephrotic syndrome (NS)
      and were resistant to steroid and conventional-dose CsA therapy. LDL-A was
      performed twice a week for 3 weeks (first course), then weekly for 6 weeks
      (second course). Beginning from the second LDL-A course, a dosage of 1 mg/kg/d of
      prednisone was administered for 6 weeks, then tapered. RESULTS: Seven patients
      experienced remission of NS, 5 of whom achieved complete remission within 4 weeks
      after initiating prednisone therapy with LDL-A. These 5 patients maintained
      normal renal function during follow-up (median, 4.4 years). Of 2 patients with
      partial remission, 1 patient maintained stable renal function during follow-up
      (4.5 years), whereas the other patient showed a gradual decline in renal function
      and progressed to end-stage renal failure (ESRF) 7.8 years after LDL-A therapy.
      Four patients who were considered to experience treatment failure had persistent
      NS and progressed to ESRF in 1.3 years (median) after LDL-A therapy. Complete
      remission (n = 5) was associated with significantly more highly selective
      proteinuria compared with treatment failure (n = 4). CONCLUSION: This study
      suggests that combined LDL-A and prednisone therapy can be a valuable addition to
      therapeutic options for treating patients with SR-FSGS. The role of LDL-A in
      treating these patients deserves to be assessed further in larger randomized
      controlled trials.

PMID- 14655183
TI  - Predicting the prognosis of renal dysfunction by renal expression of alpha-smooth
      muscle actin in children with MPGN type 1.
AB  - BACKGROUND: To clarify whether renal alpha-smooth muscle actin (alpha-SMA)
      positive cell and macrophage accumulation can predict the prognosis of renal
      dysfunction, we evaluated them by means of multivariate analysis and compared
      them with other clinical predictors in patients with membranoproliferative
      glomerulonephritis (MPGN) type 1 with normal renal function. METHODS: We enrolled
      35 patients with MPGN type 1 who had normal creatinine clearance at the time of
      renal biopsy. These patients were divided into 2 groups based on clinical status
      at the last examination. Group 1 consisted of 12 patients with normal urine and
      12 patients with minor urinary abnormalities at the latest observation, whereas
      group 2 consisted of 7 patients with persistent nephropathy and 4 patients with
      renal insufficiency. The first and second renal biopsy findings, including alpha
      SMA and CD68-positive staining, were investigated for both groups. RESULTS: Mean
      scores for glomerular and interstitial alpha-SMA staining in group 2 were
      significantly higher than those in group 1. At the second biopsy, mean scores for
      interstitial CD68-positive staining in group 2 were higher than those in group 1.
      Mean scores for glomerular and interstitial alpha-SMA at the first biopsy
      correlated with the chronicity index at the second biopsy in both groups.
      CONCLUSION: Our results suggest that glomerular and interstitial alpha-SMA
      expression at the first biopsy can predict the prognosis of children with MPGN
      type 1.

PMID- 14655184
TI  - Decreased expression of vascular endothelial growth factor in idiopathic
      membranous glomerulonephritis: relationships to clinical course.
AB  - BACKGROUND: Membranous glomerulonephritis (MGN) has a variable clinical course,
      and factors that determine the prognosis are unknown. Our previous study
      suggested that urinary excretion of vascular endothelial growth factor (VEGF) is
      decreased in active MGN, but normalizes in remission. In the present study, VEGF
      protein and messenger RNA (mRNA) expression were investigated in this disease.
      METHODS: Twelve patients with clinically active and/or progressive MGN were
      studied by using urinary assays for VEGF and soluble VEGF receptor-1 (sVEGF-R1),
      semiquantitative scoring of serial renal biopsy specimens by using
      immunohistochemical staining for VEGF protein, and in situ hybridization for VEGF
      mRNA. Results were compared with healthy controls and normal parts of
      nephrectomized kidneys. RESULTS: Urinary VEGF excretion was decreased
      significantly (P < 0.001 versus controls) in MGN, but there was no difference in
      sVEGF-R1 excretion compared with healthy subjects. VEGF protein expression was
      diminished significantly in glomerular podocytes (P = 0.008), as well as in
      extraglomerular small arteries (P = 0.03) and arterioles (P = 0.008) in MGN.
      Total kidney VEGF score (the sum of scores of individual kidney compartments)
      also was decreased in MGN (P < 0.05) and remained low in repeated biopsies.
      Expression of VEGF mRNA localized predominantly to podocytes in normal kidneys
      was greatly reduced in MGN. CONCLUSION: Clinically active MGN is associated with
      diminished expression of VEGF protein and mRNA, mainly in podocytes, and
      expression remains depressed in persistently active and/or progressive disease.
      This is reflected by decreased urinary VEGF excretion. These findings point to
      potentially reversible podocyte injury and, together with our previous study,
      suggest that VEGF may have a protective role during the evolution of MGN.

PMID- 14655185
TI  - Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small
      vessel vasculitis.
AB  - BACKGROUND: Unlike Goodpasture's syndrome with diffuse alveolar hemorrhage (DAH),
      there are few studies examining therapy for patients with DAH associated with
      antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis
      (SVV). METHODS: We performed a retrospective review of all such patients
      presenting to our institution between 1995 and 2001. All patients were treated
      with apheresis and induction immunosuppressive therapy; namely, intravenous
      methylprednisolone and/or intravenous cyclophosphamide. RESULTS: DAH resolved
      with apheresis in 20 of 20 patients (100%) with 6.4 (average) treatments. There
      were no complications of therapy. Half the patients (7 of 14) who also presented
      with azotemia were discharged with improved renal function. CONCLUSION: Patients
      with ANCA-related SVV and DAH benefit from prompt initiation of apheresis coupled
      with aggressive immunosuppressive therapy. Such therapy can be lifesaving with
      respect to the pulmonary component of this syndrome.

PMID- 14655186
TI  - Light chain deposition disease with renal involvement: clinical characteristics
      and prognostic factors.
AB  - BACKGROUND: Light chain deposition disease (LCDD) is characterized by the tissue
      deposition of monotypical immunoglobulin light chains (LCs). The aim of this
      study was to investigate its clinical characteristics and prognostic factors.
      METHODS: Multicenter study of LCDD with renal and patient survival analyses.
      RESULTS: Sixty-three cases were studied (age: 58 +/- 14.2; males: 63.5%;
      kappa/lambda deposition: 68/32%; underlying disorders: multiple myeloma [MM] 65%,
      lymphoproliferative disorders 3%, idiopathic 32%). Ninety-six percent presented
      with renal insufficiency (acute, 52%; chronic, 44%), and 84% with proteinuria >1
      g/d. During the follow-up, 36 patients reached uremia (incidence rate: 23.7/100
      patient-years) and 37 died (17.5/100 patient-years). The factors independently
      associated with a worse renal prognosis were age (relative risk [RR], 1.05; 95%
      confidence interval [CI], 1.009 to 1.086) and serum creatinine at presentation
      (RR, 1.24; 95% CI, 1.02 to 1.5). Those independently associated with a worse
      patient survival were age (RR, 1.06; 95% CI, 1.03 to 1.1), MM (RR, 2.75; 95% CI,
      1.22 to 6.2), and extrarenal LC deposition (RR, 2.24; 95% CI, 1.15 to 4.35).
      While kappa-LC deposition was more frequently associated with nodular sclerosing
      glomerulopathy, histological parameters were not predictors of renal/patient
      prognosis. The survival of the uremic patients undergoing dialysis was similar to
      that of patients not reaching uremia. CONCLUSION: LCDD is characterized by renal
      insufficiency with proteinuria and has a severe prognosis. Apart from age, the
      prognostic factors identified were degree of renal insufficiency at presentation
      affecting the renal prognosis, underlying hematologic disorder and extrarenal LC
      deposition affecting the patient prognosis. Dialysis is worth performing in
      uremic LCDD patients.

PMID- 14655187
TI  - Renal tubular dysfunction in beta-thalassemia minor.
AB  - BACKGROUND: Persons with beta-thalassemia minor usually are symptomless. However,
      we previously reported renal tubular dysfunction in a patient with beta
      thalassemia minor. The aim of this study is to investigate renal function in
      patients with beta-thalassemia minor. METHODS: Forty-one subjects with beta
      thalassemia minor and 20 sex- and age-matched healthy subjects were enrolled in
      the study. For analysis, patients were divided into 2 groups: group A, all
      patients with anemia (n = 19), and group B, patients without anemia (n = 22).
      Blood and 24-hour urine samples were obtained for hematologic and biochemical
      analysis. RESULTS: Anemic patients had increased urinary zinc excretion (U(zinc))
      and fractional excretion of sodium (FE(Na)) and uric acid (FE(UA)) compared with
      both controls and patients without anemia. Hemoglobin levels correlated
      significantly in a negative manner with U(zinc), FE(Na), and FE(UA) in patients
      with beta-thalassemia minor. However, serum lactate dehydrogenase levels
      correlated significantly in a positive manner with the same parameters. In
      addition, 6 of 41 patients (14.6%) with beta-thalassemia minor showed significant
      signs of renal tubulopathy, such as hypercalciuria, decreased tubular
      reabsorption of phosphorus with hypophosphatemia, hypomagnesemia with renal
      magnesium wasting, hypouricemia with renal uric acid wasting, and tubular
      proteinuria. CONCLUSION: Proximal renal tubular dysfunction is not rare in
      patients with beta-thalassemia minor.

PMID- 14655188
TI  - Prediction of GFR in liver transplant candidates.
AB  - BACKGROUND: Kidney function frequently is impaired in patients with cirrhosis;
      however, glomerular filtration rate (GFR) is difficult to estimate in these
      patients by using standard clinical markers. The aim of our study is to compare
      GFR calculated from renal clearance of iodine 125-labeled iothalamate ((125)I
      iothalamate) with the plasma decay technique and the Modification of Diet in
      Renal Disease (MDRD) and Cockroft-Gault (CG) prediction equations. METHODS: We
      performed a cross-sectional study of patients with liver cirrhosis being
      evaluated for transplantation (50% Child's class C); 89% had ascites or edema and
      44% were men aged 55 +/- 2 years. Average pretest blood urea nitrogen level was
      16 +/- 2 mg/dL (5.7 +/- 0.7 mmol/L); serum creatinine, 1.0 +/- 0.1 mg/dL (88 +/-
      9 micromol/L; range, 0.6 to 1.7 mg/dL [53 to 150 micromol/L]); plasma albumin,
      3.14 +/- 0.16 g/dL (31.4 +/- 1.6 g/L); and total bilirubin, 4.0 +/- 0.7 mg/dL (67
      +/- 11.3 micromol/L). Kidney function was measured by means of simultaneous
      plasma and renal clearance of (125)I-iothalamate (Glofil-125; Cypros
      Pharmaceutical Corp, Carlsbad, CA) and the MDRD and CG equations. RESULTS: GFRs
      were 58.2 +/- 5.1 mL/min/1.73 m(2) by renal clearance of (125)I-iothalamate and
      76.7 +/- 7.2 mL/min/1.73 m(2) by the plasma decay technique (+18.5 mL/min, or
      32%; P = 0.0004). GFR by the MDRD equation was 76.9 +/- 7.8 mL/min/1.73 m(2)
      (+18.7 mL/min, or 32%; P = 0.0004 versus renal iothalamate; r(2) = 0.57). GFR by
      the CG equation was the least accurate (+30.1 mL/min, or 52%; P = 0.0001 versus
      renal iothalamate). CONCLUSION: The current clinically used CG and MDRD equations
      to estimate kidney function in patients with cirrhosis and volume excess and the
      (125)I-iothalamate plasma decay technique are inaccurate because they
      overestimate GFR. It seems very unlikely that accurate and reliable formulas will
      be developed that are able to replace the formal measurement of GFR in patients
      with liver cirrhosis. Therefore, we conclude that despite the additional
      complexity, renal clearance techniques should be used to assess GFR accurately in
      patients with liver cirrhosis and ascites.

PMID- 14655189
TI  - Intestinal calcium absorption is associated with bone mass in stone-forming women
      with idiopathic hypercalciuria.
AB  - BACKGROUND: Patients with idiopathic hypercalciuria are predisposed to
      osteoporosis despite their high enteral calcium absorption. Conversely, low
      calcium absorption has been reported in patients with osteoporosis. Because bone
      loss occurs earlier in women, this work explores the relationship between bone
      mineral density (BMD) and calcium absorption in premenopausal and postmenopausal
      hypercalciuric stone-forming women. METHODS: BMD and intestinal calcium
      absorption were compared in 64 hypercalciuric and 42 normocalciuric calcium stone
      forming women. Calcium absorption was assessed by using strontium as a surrogate
      marker for calcium. Strontium was administered to patients as an oral load, then
      measured in blood to calculate absorption after 60 minutes. Femoral and lumbar
      spine BMD were measured by dual-energy x-ray absorptiometry. RESULTS: Strontium
      absorption was significantly increased in hypercalciuric stone formers, whereas
      BMD z score was decreased in hypercalciuric patients at the lumbar spine, but not
      the femur. The increase in strontium absorption was detected in both
      postmenopausal (n = 29) and premenopausal (n = 35) hypercalciuric patients. The
      decrease in lumbar-spine BMD was confirmed in postmenopausal, but not
      premenopausal, hypercalciuric patients. Strontium absorption was greater in
      hypercalciuric patients with a lumbar-spine BMD z score of -2 or less (n = 10)
      than in those with a score greater than -2 (n = 54). Multiple stepwise regression
      showed that lumbar-spine BMD was related negatively to intestinal strontium
      absorption and age in hypercalciuric patients. CONCLUSION: Results of the
      strontium absorption test suggest that the increase in calcium absorption is
      associated with a decrease in lumbar-spine BMD in hypercalciuric stone-forming
      women. Hypercalciuric stone-forming women with high calcium intestinal absorption
      denote a group of patients predisposed to loss of bone mass.

PMID- 14655190
TI  - Stage of chronic kidney disease predicts seroconversion after hepatitis B
      immunization: earlier is better.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection remains a concern in dialysis
      populations, and vaccination programs have been less successful than those in the
      general population. Reasons for poor response include malnutrition, uremia, and
      the generalized immunosuppressive state of patients with chronic kidney disease
      (CKD). This prospective cohort study evaluated factors impacting on the
      effectiveness of a vaccination program before dialysis therapy initiation,
      including level of kidney function. METHODS: All patients receiving care in the
      Kidney Function Clinic (St Paul's Hospital, Vancouver, Canada) were screened for
      previous HBV infection or vaccination. Those who were marker negative were
      administered a standardized hepatitis B vaccination schedule recommended for
      patients with CKD. The primary outcome measure, seroconversion, is defined as
      hepatitis B surface antibody titer greater than 10 IU 3 months after completion
      of the vaccination schedule. RESULTS: The study population of 165 patients
      included 64% men with a mean age of 60 years, mean serum creatinine level of 3.4
      +/- 1.5 mg/dL (300 +/- 133 micromol/L), and median estimated glomerular
      filtration rate (GFR) of 20 mL/min (interquartile range, 14 to 20).
      Seroconversion rate was 82%. Multivariate analyses showed the independent
      predictive value of level of GFR. The model showed that patients with the lowest
      level of kidney function and who were older and had diabetes were less likely to
      seroconvert (P < 0.05). CONCLUSION: This is the largest study to show in a well
      characterized cohort that patients with higher GFR levels are more likely to
      respond to hepatitis B vaccination programs with seroconversion, independent of
      other factors. Future studies will explore specific mechanisms to explain this
      phenomenon.

PMID- 14655191
TI  - Evolution of naturally acquired hepatitis B immunity in the long-term
      hemodialysis population.
AB  - BACKGROUND: Although the natural history of vaccination-induced hepatitis B virus
      (HBV) antibodies (Abs) is becoming clearer, little is known about naturally
      acquired immunity. Some assume that these patients never lose their Abs. METHODS:
      To document the natural history of HBV immunity, we prospectively followed up all
      naturally immune patients initiating hemodialysis (HD) therapy at St Michael's
      Hospital (Toronto, Canada). Patients presenting with Ab to hepatitis B surface
      antigen (HBsAb) who had no history of vaccination had a core Ab level measured to
      confirm natural immunity. When HBsAb titer decreased to less than 10 IU/L,
      patients were administered a single dose of 40 microg of Engerix B vaccine (Smith
      Kline Beecham Pharma Inc, Oakville, Ontario, Canada) intramuscularly as a booster
      dose. RESULTS: We identified 29 patients beginning HD therapy with natural
      immunity. Nine patients (30%) subsequently lost immunity (defined as Ab titer
      decreasing to < 10 IU/L) during follow-up. They were older and had a lower Ab
      titer at initiation of HD therapy. Four of 5 patients with a low response to the
      booster dose were 75 years or older. Two patients with a low peak Ab titer after
      the booster dose again had their Ab titer decrease to less than 10 IU/L after 6
      and 10 months. Both patients were switched to intradermal vaccination. All other
      patients were still immune after a median of 26 months. CONCLUSION: Individuals
      who are naturally immune against HBV may experience a decrease in Ab titer. Their
      responses to booster vaccinations varied widely. It is possible that elderly
      patients with natural immunity require closer surveillance. We provide
      recommendations for surveillance in these patients.

PMID- 14655192
TI  - Longitudinal and cross-sectional effects of C-reactive protein, equilibrated
      normalized protein catabolic rate, and serum bicarbonate on creatinine and
      albumin levels in dialysis patients.
AB  - BACKGROUND: Loss of muscle mass and hypoalbuminemia each may result in part from
      either malnutrition, inflammation, or a combination of both. Short-term acidosis
      increases muscle protein catabolism and inhibits albumin synthesis. METHODS: We
      analyzed albumin and creatinine levels as outcome variables and their association
      with C-reactive protein (CRP) level, equilibrated normalized protein catabolic
      rate (enPCR), and serum bicarbonate level as independent variables from
      laboratory data obtained from patients in the Hemodialysis Study. Analyses
      controlled for race, sex, age, body mass index, and randomized treatment group.
      RESULTS: Albumin level correlated with both enPCR and CRP level, but not serum
      bicarbonate level, in both cross-sectional and longitudinal analyses. Effects of
      CRP level and enPCR were not linear. Albumin level correlated positively with
      enPCR for an enPCR less than 1.0 g/kg/d, but not for a greater enPCR, and
      correlated inversely with CRP level for a CRP level greater than 13 mg/L.
      Similarly, creatinine level correlated with both enPCR and CRP level. As in the
      case of albumin level, effects were not linear. Creatinine level correlated
      positively with enPCR for values less than 1.0 g/kg/d, but not for greater enPCR
      values. In contrast to albumin level, creatinine level correlated negatively with
      serum bicarbonate level, even when adjusted for enPCR. CONCLUSION: Albumin and
      creatinine levels are independently associated with nutrition (enPCR) and
      inflammation (CRP level). The cross-sectional relationship with enPCR is apparent
      only at values less than 1.0 g/kg/d. CRP level is associated with reduced albumin
      and creatinine values when increased to values greater than 5.6 mg/dL. CRP may be
      increased to levels associated with increased cardiovascular risk with little or
      no effect on either serum albumin or creatinine level. Thus, a normal albumin
      level does not exclude elevated CRP levels.

PMID- 14655194
TI  - Acute effect of pamidronate on PTH secretion in postmenopausal hemodialysis
      patients with secondary hyperparathyroidism.
AB  - BACKGROUND: The purpose of this study is to evaluate the acute effect of
      pamidronate on plasma ionized calcium (iCa) level reduction and dynamic
      parathyroid hormone (PTH) secretion in postmenopausal hemodialysis-dependent
      women with secondary hyperparathyroidism. METHODS: Twelve postmenopausal women
      undergoing regular hemodialysis with serum intact PTH levels greater than 200
      pg/mL (200 ng/L) were included in this study. Pamidronate was administered
      intravenously as a single dose of 15 mg in the last hour of hemodialysis. PTH
      responses to hypocalcemia and hypercalcemia induced with 1 mEq/L (0.5 mmol/L) and
      4 mEq/L (2 mmol/L) of dialysate calcium, respectively, were evaluated before and
      1 week after pamidronate therapy. RESULTS: Pamidronate therapy resulted in a
      decrease in predialysis basal plasma iCa (iCa(base); P < 0.05) levels and an
      increase in maximal serum PTH (PTHmax; P < 0.001), basal PTH (PTHbase; P <
      0.001), and minimal PTH levels (P < 0.001). The set point of serum calcium and
      the slope of the PTH-calcium curve were not altered by pamidronate therapy. An
      inverse correlation was present between iCa(base) and the PTHbase-PTHmax ratio
      before (r = -0.66; P < 0.05) and after (r = -0.84; P < 0.001) pamidronate
      therapy. CONCLUSION: Our study shows that pamidronate therapy is associated with
      reduced plasma iCa levels and increased PTH secretion, resulting in aggravated
      secondary hyperparathyroidism. These findings suggest that secondary
      hyperparathyroidism may worsen after the administration of pamidronate, at least
      in the short term, in postmenopausal hemodialysis patients.

PMID- 14655193
TI  - Markers of inflammation, proteolysis, and apoptosis in ESRD.
AB  - BACKGROUND: Hemodialysis (HD) is associated with protein catabolism and augmented
      apoptosis. Although the effect of metabolic acidosis and inflammatory cytokines
      on activation of the ubiquitin-proteasome pathway and branched-chain keto acid
      dehydrogenase (BCKAD) is well known, the effect of HD on these pathways remains
      unexplored. METHODS: Twelve patients with end-stage renal disease were studied
      before and during HD. Eight controls also were studied. Plasma levels of
      complement components and cytokines, interleukin-1 (IL-1), IL-6, and tumor
      necrosis factor-alpha (TNF-alpha) were measured. Messenger RNA (mRNA) levels of
      caspase-3, a mediator of apoptosis; ubiquitin, a marker of proteolysis; and BCKAD
      E2, an enzyme regulating branched-chain amino acid oxidation, were estimated in
      skeletal muscle biopsy specimens by means of reverse-transcriptase polymerase
      chain reaction. Annexin-V expression was quantified by DNA array. Before the
      study, participants were placed on a 1.2-g/kg/d protein diet, and metabolic
      acidosis was corrected. RESULTS: During HD, plasma IL-6 levels increased from
      7.54 +/- 2.24 to 27.86 +/- 4.94 pg/dL (P < 0.001). Complement component, IL-1,
      and TNF-alpha levels did not change significantly during HD. mRNA levels of
      caspase-3 (0.50 +/- 0.01 versus 0.81 +/- 0.04), annexin-V (0.94 +/- 0.06 versus
      1.48 +/- 0.05; P < 0.001), ubiquitin (1.10 +/- 0.03 versus 1.44 +/- 0.03), and
      BCKAD-E2 (0.47 +/- 0.01 versus 0.81 +/- 0.04) increased in muscle during HD
      compared with pre-HD values (P < 0.001). mRNA levels of ubiquitin (0.62 +/- 0.03)
      and BCKAD-E2 (0.58 +/- 0.02) were greater in controls than pre-HD values (P <
      0.05). There were significant positive correlations between plasma IL-6 levels
      and expression of caspase-3, ubiquitin, and BCKAD-E2 genes. CONCLUSION: HD causes
      activation of cytokines, which may mediate the increase in gene expression of
      caspase-3, ubiquitin, and BCKAD-E2 in skeletal muscles.

PMID- 14655195
TI  - Cost analysis of renal replacement therapies in Finland.
AB  - BACKGROUND: Costs for treating patients with end-stage renal disease (ESRD) have
      grown noticeably. However, most of the cost estimates to date have taken the
      perspective of the payers. Hence, direct costs of treating ESRD are not
      accurately known. METHODS: Files of all adult patients with ESRD who entered
      dialysis therapy between January 1, 1991, and December 31, 1996, were studied
      retrospectively, and all use of health care resources and services was recorded.
      Follow-up continued until December 31, 1996. RESULTS: Two hundred fourteen
      patients fulfilled the study criteria, 138 patients started with in-center
      hemodialysis (HD) therapy, and 76 patients started with continuous ambulatory
      peritoneal dialysis (CAPD) therapy. Patients were followed up until death (72
      patients) or treatment modality changed for more than 1 month. Fifty-five
      patients received a cadaveric transplant, and after transplantation (TX), they
      were examined as a separate group of TX patients. Direct health care costs for
      the first 6 months in the HD, CAPD, and TX groups were 32,566 US dollars, 25,504
      dollars, and 38,265 dollars, and for the next 6 months, 26,272 dollars, 24,218
      dollars, and 7,420 dollars, respectively. During subsequent years, annual costs
      were 54,140 US dollars and 54,490 dollars in the HD group, 45,262 dollars and
      49,299 dollars in the CAPD group, and 11,446 dollars and 9,989 dollars in the TX
      group. Regression analyses showed 4 variables significantly associated with
      greater daily costs in dialysis patients: age, ischemic heart disease, nonprimary
      renal disease, and HD treatment. CONCLUSION: Compared with HD, CAPD may be
      associated with lower costs, yet the absolute difference is not striking. After
      the TX procedure is performed once, annual costs decline remarkably, and
      cadaveric TX is less costly than both dialysis modalities.

PMID- 14655196
TI  - Pain in hemodialysis patients: prevalence, cause, severity, and management.
AB  - BACKGROUND: There is growing evidence that dialysis patients have a high burden
      of symptoms, including pain. However, the prevalence, cause, severity, and
      management of pain in dialysis patients have not been described. METHODS: This
      prospective cohort study of 205 Canadian hemodialysis (HD) patients describes the
      prevalence, cause, severity, and management of pain in this population. A chart
      review for demographic and clinical data was conducted, and patients completed a
      questionnaire that incorporated the Brief Pain Inventory, followed by the McGill
      Pain Questionnaire. RESULTS: One hundred three patients (50%) reported a problem
      with pain. Patients with pain had been on HD therapy longer (52.2 months) than
      those without pain (37.7 months). Causes of pain were diverse, and 18.4% of
      patients had more than a single cause of their pain. Musculoskeletal pain was
      most common (50.5%) and equal in severity to pain associated with peripheral
      neuropathy and peripheral vascular disease. Fifty-five percent of patients with
      pain rated their worst episode in the previous 24 hours as severe. Thirty-two
      percent of patients with pain were administered no analgesics, 29.1% were
      administered nonopioid analgesics, 26.2% were administered weak opioids, and 9.7%
      were administered strong opioids. The Pain Management Index describes the
      effectiveness of pain management and was negative in 74.8% of patients,
      indicating ineffective management. CONCLUSION: Pain is a significant problem in
      more than 50% of HD patients and is not being effectively managed. The
      development of effective pain management strategies, underpinned by appropriate
      training and education, is necessary to improve the quality of life for dialysis
      patients.

PMID- 14655197
TI  - Pediatric convective hemofiltration: Normocarb replacement fluid and citrate
      anticoagulation.
AB  - BACKGROUND: Continuous venovenous hemofiltration (CVVH) may be preferable over
      continuous venovenous hemodialysis (CVVHD) in sepsis; however, CVVH use is
      limited by the lack of commercially produced bicarbonate replacement solutions in
      the United States. Anticoagulation used for hemofiltration traditionally has been
      either heparin or citrate based, but to date, citrate protocols have been used
      predominately in CVVHD. When CVVH has been used with citrate anticoagulation,
      replacement solutions have had to be custom made in the pharmacy. METHODS: We
      describe a protocol used in a series of 9 children with sepsis who underwent CVVH
      with the use of a commercially available bicarbonate solution (Normocarb;
      Dialysis Solutions Inc, Richmond Hill, Ontario, Canada) and a commercially
      available citrate solution (Anticoagulant Citrate Dextrose Solution Formula A
      [ACD-A]; Baxter Health Care, Deerfield, IL). This simplified approach to citrate
      anticoagulation with CVVH used Normocarb as a prefilter replacement solution
      under provisions of the 1997 Food and Drug Administration Modernization Act.
      RESULTS: All patients had acceptable levels of solute and ultrafiltration
      clearance with this approach. CVVH circuit life averaged 71 hours (range, 37 to
      131 hours), influenced in part by the industry recommendation to change the
      circuit at 72 hours, whereas no complications from this protocol were identified.
      CONCLUSION: Similar to CVVHD, this protocol is effective and simple in its
      components, using industry-produced solutions, avoiding the need for pharmacy
      made solutions, and limiting cost and potential risk for compounding errors.
      Although not the purpose of this report, the patient survival rate was 55%.

PMID- 14655198
TI  - Effects of sevelamer hydrochloride and calcium acetate on the oral
      bioavailability of ciprofloxacin.
AB  - BACKGROUND: The oral bioavailability of ciprofloxacin is significantly decreased
      when administered with calcium carbonate. Sevelamer hydrochloride is a phosphate
      binding cationic polymer that is devoid of calcium. The authors conducted a 3
      way, randomized, crossover study to determine the effects of sevelamer
      hydrochloride and calcium acetate on the relative oral bioavailability of
      ciprofloxacin. METHODS: Fifteen healthy volunteers were assigned randomly to
      receive each of the following oral regimens: ciprofloxacin 750 mg, alone (Arm A);
      ciprofloxacin 750 mg plus 7 sevelamer hydrochloride 403 mg capsules (Arm B);
      ciprofloxacin 750 mg plus 4 calcium acetate 667 mg tablets (Arm C). Serial blood
      and urine samples were obtained over 24 hours, and ciprofloxacin concentrations
      were determined by high-performance liquid chromatography. Pharmacokinetic data
      were analyzed using noncompartmental methods, and maximum serum concentration
      (Cmax) and area under the serum concentration time curve from 0 to infinity
      (AUC(0- infinity )) were tested for bioequivalence after log transformation of
      the data. The relative oral bioavailability of ciprofloxacin was calculated as
      AUC(0- infinity ), Arm B or Arm C/AUC(0- infinity ), Arm A. RESULTS: The Cmax and
      AUC(0- infinity ) of ciprofloxacin were significantly decreased when administered
      concomitantly with sevelamer hydrochloride or calcium acetate (P < 0.05), and
      bioequivalence was not achieved for either parameter. The relative oral
      bioavailability of ciprofloxacin was decreased by 48% with sevelamer
      hydrochloride and 51% with calcium acetate (P < 0.05). CONCLUSION: The relative
      oral bioavailability of ciprofloxacin is significantly decreased when
      administered with sevelamer hydrochloride or calcium acetate. Concomitant
      administration of these drugs may decrease clinical efficacy and promote
      bacterial resistance to ciprofloxacin.

PMID- 14655199
TI  - Characteristics of treated hypertension in incident hemodialysis and peritoneal
      dialysis patients.
AB  - BACKGROUND: The treatment of hypertension in dialysis patients is prevalent and
      poorly characterized. beta-Blockers and calcium channel blockers (CCBs) have been
      associated with reduced all-cause and cardiovascular mortality. This study
      describes the treatment of hypertension and assesses the association between
      mortality and class of antihypertensive medication among a cohort of dialysis
      patients. METHODS: The US Renal Data System (USRDS) Dialysis Morbidity and
      Mortality Study Wave II cohort was analyzed. A total of 2,877 patients initiating
      hemodialysis or peritoneal dialysis in 1996 or 1997 and treated with
      antihypertensives were included in this analysis. Vital status was followed until
      November 2000. RESULTS: Calcium channel blockers were prescribed to 70.3% of
      patients. Only 31.5% and 27.0% of patients with cardiovascular disease were
      prescribed angiotensin-converting enzyme inhibitors and beta-blockers,
      respectively. Mono-, double-, triple-, and more than triple-therapy were reported
      in 48.0%, 36.1%, 13.2%, and 2.7% of the cohort, respectively. In multivariable,
      fully adjusted models, no individual class of antihypertensives was associated
      with changes in all-cause mortality. In all patients, nondihydropyridine CCBs
      (non-DHP CCBs) were associated with a reduced risk of cardiovascular death
      (hazard ratio, 0.78; 95% confidence interval, 0.62 to 0.97) and among end-stage
      renal disease patients with preexisting cardiovascular disease, dihydropyridine
      CCBs (DHP CCBs) and non-DHP CCBs were associated with reduced risk of all-cause
      and cardiovascular mortality. CONCLUSION: Calcium channel blocker use is
      widespread among hypertensive dialysis patients. Antihypertensive prescription
      patterns suggest a lack of consensus regarding treatment of hypertension.
      Multivariable analysis of associations between antihypertensive class and
      mortality reveals results of uncertain clinical significance. Hypertension
      treatment trials in dialysis patients should be performed to appropriately inform
      treatment decisions.

PMID- 14655200
TI  - Peritoneoscopic placement of peritoneal dialysis catheter and bowel perforation:
      experience of an interventional nephrology program.
AB  - BACKGROUND: Bowel perforation is an uncommon but serious complication of
      peritoneoscopic peritoneal dialysis (PD) catheter insertion. The approach to
      diagnosis of bowel perforation utilizing this technique has not been previously
      published. The authors report their experience with the diagnosis and management
      of bowel perforation in the context of peritoneoscopic placement of PD catheters.
      METHODS: The authors retrospectively reviewed the records of 750 PD catheters
      inserted over a 12-year period (January 1991 to May 2003) utilizing
      peritoneoscopic technique. RESULTS: Six (0.8%) patients experienced bowel
      perforation during the procedure. The diagnosis was made immediately during the
      procedure in 5 (83%) of the 6 patients. Of these 5, peritoneoscopy confirmed
      intrabowel position of the cannula by visualizing bowel mucosa (n = 3) and hard
      stool (n = 1). The fifth patient showed extrusion of fecal matter upon trocar
      withdrawal before peritoneoscopy. All 5 had emanation of foul-smelling gas
      through the cannula. Bowel rest and broad-spectrum intravenous antibiotics were
      initiated. Of the 5, 1 required surgery, whereas the others were discharged home
      after 3 days. The sixth patient had fever, severe peritoneal irritation, and
      polymicrobial peritonitis the morning after the procedure. In this patient, no
      evidence of bowel injury was noted during the procedure except for brief
      emanation of foul-smelling gas. He required surgical intervention. CONCLUSION:
      Bowel perforation can be diagnosed immediately in most patients undergoing
      peritoneoscopic PD catheter insertion. A majority of these patients can be
      treated medically. The surgical team should be consulted if the patient shows
      clinical deterioration or has signs of peritoneal irritation.

PMID- 14655201
TI  - The impact of residual renal function on graft and patient survival rates in
      recipients of preemptive renal transplants.
AB  - BACKGROUND: Transplantation before the initiation of dialysis is associated with
      prolonged allograft survival. It is unclear if this benefit is attributable to
      greater residual renal function or to avoidance of dialysis exposure. The authors
      performed an analysis to determine whether higher renal function at transplant
      was associated with increased patient and graft survival rates. METHODS: The
      authors identified individuals who between 1994 and June 2000 were >or= 18 years
      and had undergone a living donor renal transplant (Tx) as initial form of renal
      replacement therapy. Pre-Tx and 6-month estimated glomerular filtration rates
      (eGFR) were calculated using the 4-variable Modification of Diet in Renal Disease
      formula. Survival was compared in those with a pre-Tx eGFR >or=15mL/min to those
      with an eGFR less than 15 mL/min, after adjusting for demographic variables, co
      morbidities, and transplant characteristics. Survival rate then was adjusted for
      calculated propensity scores. RESULTS: A total of 4,046 patients were included.
      Mean pre-Tx eGFR was 9.9 mL/min (0.9 to 57.1 mL/min). There was no difference in
      graft survival rates by strata of eGFR in any of the tested models, even after
      correcting for propensity score (hazard ratio, 0.95; 95% confidence interval,
      0.69 to 1.30). There was no correlation between pre-Tx eGFR and 6-month post-Tx
      eGFR (r(2) =-0.005). CONCLUSION: Recipients of preemptive transplants fare
      equally, regardless of the eGFR at which they receive their transplant. There was
      no relationship between pre-Tx eGFR and 6-month eGFR, suggesting that post-Tx
      renal function is independent of the level of pre-Tx renal function. These data
      suggest that preemptive kidney transplantation should be delayed as long as
      possible, provided the patient does not have uremic symptoms, and dialysis can be
      safely avoided.

PMID- 14655202
TI  - Dysarthria in a patient with probable acquired chloridorrhea.
AB  - The authors encountered a patient who had profound hypochloremic metabolic
      alkalosis after developing profuse diarrhea related to rejection of her small
      bowel transplant. Her ileostomy fluid showed massive electrolyte losses and was
      exceptionally high in chloride content. She improved with volume substitution and
      a proton pump inhibitor, although she subsequently required repeat small bowel
      transplant. The authors speculate that an impaired "downregulated in adenoma"
      gene (DRA) that enclodes an apical Cl(-)/HO(-)(HCO(3)) exchanger may have
      contributed to an acquired chloridorrhea in this patient.

PMID- 14655203
TI  - Two male siblings with hereditary renal hypouricemia and exercise-induced ARF.
AB  - Familial renal hypouricemia with exercise-induced acute renal failure (ARF) is
      rare. A 45-year-old man presented with abdominal pain, vomiting, and oliguria
      after severe exercise. The diagnosis was ARF based on high serum creatinine (SCr)
      level (5.1 mg/dL [451 micromol/L]). Renal function recovered completely within 2
      weeks of conservative treatment (creatinine clearance [Ccr], 100.4 mL/min [1.67
      mL/s]). After remission, laboratory results showed serum urate (SUA) of 0.8 mg/dL
      (48 micromol/L), and fractional excretion of uric acid (FE(UA)) of 46%. The final
      diagnosis was ARF associated with idiopathic renal hypouricemia. Other diseases
      that could increase the excretion of urate were excluded. Because only mild
      responses were observed both in pyradinamide and benzbromarone loading tests, he
      was considered to be a presecretory reabsorption disorder type. The younger
      brother (42 years old) also had episodes of low and middle back pain after severe
      exercise and experienced similar attacks at least 5 times since the age of 29.
      SCr level was elevated in every attack. Hypouricemia (SUA, 1.0 mg/dL [59
      micromol/L]) and high urinary urate excretion (FE(UA), 65.7%) also were detected.
      Renal function recovered almost completely without any specific treatment.
      Radiologic examination of the 2 cases showed bilateral urolithiasis probably
      caused by the high urinary urate excretion. Sequence analysis of a urate anion
      exchanger known to regulate blood urate level (URAT1 gene) in both brothers
      showed homozygous mutation in exon 4 (W258Stop), resulting in a premature
      truncated URAT1 protein. Both their parents and their children showed
      heterozygous mutation of the URAT1 gene. This is the first report of the 2 male
      siblings of familial renal hypouricemia complicated with exercise-induced ARF,
      with definite demonstration of genetic abnormality in the responsible gene
      (URAT1).

PMID- 14655204
TI  - Arteriovenous fistula creation: should US nephrologists get involved?

PMID- 14655205
TI  - Are antihypertensive drugs used to maximally reduce cardiovascular risk in
      dialysis patients?

PMID- 14655206
TI  - Cystic and inherited kidney diseases.

PMID- 14655207
TI  - Nephrotic syndrome in the newborn.

PMID- 14655210
TI  - Lipoprotein(a): atherogenesis linked to thrombosis and inflammation at last?

PMID- 14655211
TI  - Ofloxacin clearance during continuous hemofiltration.

PMID- 14655222
TI  - Monoclonal immunoglobin deposition disease, heavy chain deposition type.

PMID- 14655224
TI  - Gabapentin-induced hypoglycemia in a long-term peritoneal dialysis patient.
AB  - An end-stage renal disease patient on long-term peritoneal dialysis was admitted
      with dizziness, fatigue, hypoglycemia, and hypotension. The hypotension resolved
      with intravenous normal saline, but the hypoglycemia persisted for 3 days despite
      an intravenous dextrose drip and discontinuation of gabapentin. The patient
      became normoglycemic on the fourth day of admission. None of the known causes for
      the hypoglycemia were identified except gabapentin, the dose of which was
      recently doubled 1 month before admission. Insulin and C-peptide levels were high
      during the hypoglycemic episode and returned to normal after discontinuation of
      gabapentin. The patient remains off gabapentin and has had no further episodes of
      hypoglycemia. To our knowledge, this is the first case of hypoglycemia induced by
      gabapentin.

PMID- 14655225
TI  - Immunotactoid glomerulopathy in an HIV-positive African-American man.
AB  - The authors report the first case of immunotactoid glomerulopathy (ITG) in a
      human immunodeficiency virus (HIV)-positive, hepatitis B- and C-negative African
      American man who presented with hematuria and proteinuria. His initial
      presentation was compatible with HIV associated nephropathy, but on renal biopsy
      he was found to have ITG. He has been treated with highly active antiretroviral
      therapy and an angiotensin-converting enzyme inhibitor, but his proteinuria has
      not responded after 4 months of treatment. This case emphasizes the diverse
      glomerular lesions seen in HIV-positive patients and supports the use of renal
      biopsy to establish a diagnosis.

PMID- 14655227
TI  - Can patients accurately read a visual analog pain scale?
AB  - The objective of this study was too determine if patients can accurately read a
      visual analog scale (VAS) for pain. A 100-mm visual analog pain scale designed
      for patient use was printed on the top page of carbonless copy paper with a
      perfectly aligned hatched scale on the second (bottom) page. Patients over the
      age of 18 in acute pain were enrolled in this prospective, descriptive study.
      Patients were asked demographic questions and to indicate their pain severity
      with a single mark through the 100-mm scale. Once scored, patients were asked to
      read the number from the hatched bottom scale. Two physician-raters, blinded to
      patients' and each other's readings, then scored the VAS. Analysis of physician
      interrater reliability and correlation of patient and physician readings was
      performed. One hundred forty-five patients were enrolled. Seventy-nine patients
      (54.5%) read the VAS exactly as physician-readers. One hundred thirty-eight
      (95.2%) read their VAS within +/-2 mm of physician readings. Ninety-five percent
      of patients are able to read a VAS within +/-2 mm of physician readings. The data
      suggests this instrument could be used by discharged patients in longitudinal
      pain studies or with help in management of chronic pain.

PMID- 14655226
TI  - Identification of novel mutations in Na-Cl cotransporter gene in a Korean patient
      with atypical Gitelman's syndrome.
AB  - The authors report the case of a 20-year-old man with unexplained hypokalemia and
      metabolic alkalosis suggesting hypokalemic tubulopathy. Interestingly, he showed
      a mixed phenotype of Gitelman's syndrome (GS) and Bartter's syndrome, which
      includes normomagnesemia, normal renal magnesium excretion, and hypocalciuria.
      Renal clearance study showed the presence of a critical defect in the distal
      nephron rather than loop of Henle. Further family study showed that his mother
      had a definitive phenotype of GS. By the molecular genetic analysis of these
      patients, 7 different mutations of the NCCT gene were identified consisting of 3
      missense, 1 splice site, and 3 silent mutations. Four of these mutations were
      novel. The authors emphasize that the combination of a molecular genetic approach
      and renal clearance study could be of practical benefit in confusing clinical
      setting and support new diagnostic criteria in GS.

PMID- 14655228
TI  - Accuracy of portable quantitative capnometers and capnographs under prehospital
      conditions.
AB  - This study was designed to assess the pCO(2) accuracy of portable mainstream
      (Tidal Wave, Novametrix; Propaq 106, Protocol) and sidestream capnometers
      (Capnocheck 8200, BCI; Capnocount mini, Weinmann; NPB-75, Nellcor Puritan
      Bennett; SC-210, Pryon) with respect to international standards and preclinical
      emergency conditions. Measurements were performed under temperature conditions of
      +22 degrees C and -20 degrees C using dry gas mixtures with different CO(2)
      concentrations (STPD) and in patients ventilated with pure oxygen (BTPS).
      Accuracy presented to be between +1% (Capnocheck) and +12% (Propaq) (STPD) and
      between -0.4% (Capnocheck) and +11% (Tidal Wave) (BTPS). The measurements were
      affected by low ambient temperature only in the NPB-75 (+15%). Our results
      indicate that portable quantitative capnometers are able to fulfill accuracy
      requirements as requested by international standards but can be affected by
      changing ambient temperatures.

PMID- 14655229
TI  - Prevalence of significant intraocular sequelae in blunt orbital trauma.
AB  - The purpose of this study was to describe the prevalence of significant
      intraocular sequelae (SIOS) and its correlation with the severity of blunt
      orbital trauma. Four hundred ten consecutive patients presenting to the ED who
      had sustained blunt orbital trauma were studied. The severity of orbital trauma
      was graded and SIOS was determined by the presence of an intraocular injury as
      listed in Table 2. The presence of SIOS was noted in 14 (41.2%) mild, 22 (59.5%)
      moderate, and 20 (29.4%) severe orbital trauma. In the severe group, the presence
      of SIOS was detected in 8 (23.5%) blowout fractures and in 12 (35.3%) non-blowout
      fractures. In view of the high rates of ocular complications among mild and
      moderate orbital injuries, such patients should have prompt ophthalmic follow up.
      The relatively low prevalence of SIOS in patients with severe orbital trauma
      could suggest a protective mechanism in this type of injury.

PMID- 14655230
TI  - A national survey of observation units in the United States.
AB  - The objective of this study was to survey the use of observation units (OUs) in
      the United States. A written survey was mailed to every third hospital
      (sequential by zip code) in the United States. There was a 32.9% response to the
      survey (522 of 1588 hospitals). A total of 18.8% of hospitals had an OU with
      another 11.6% planning to open an OU. Those hospitals that had OUs had a higher
      overall ED census, higher rate of diversion of ambulances, and were more likely
      to be in metropolitan areas (P <.05), but there was no relationship to payor mix
      or to ED hospital admission rate. The OUs were characterized by a mean 4.8 years
      in existence, 57.3% ED administratively responsible, 59.4% ED clinically
      responsible, a mean of 1330 patients per year, an average length of stay of 15.3
      hours, a 4.2 nurse-to-patient ratio, and 22.3% hospital admission rate.

PMID- 14655231
TI  - Demand on ED resources during periods of widespread influenza activity.
AB  - The purpose of this study was to investigate ED resource demand during periods of
      Centers for Disease Control and Prevention (CDC)-declared widespread influenza
      activity (WIA). An observational analysis of secondary data describing ED
      resource demand was performed using computerized ED patient data over a 130-week
      period. Measures of ED resource utilization were compared during WIA and non-WIA
      periods. These measures included weekly census; percentage of patients triaged as
      having fever, infection, or respiratory (flu index) chief complaints; admission
      rate, ED LOS (length of stay), total bed time (TBT), the number of patients who
      left the ED without being seen by a physician (LWBS), and ED saturation time. The
      study included 34 weeks of CDC-designated WIA occurring over 3 distinct periods.
      During WIA, the flu index was elevated, 23% (95% confidence interval [CI], 20-25)
      versus 17% (95% CI, 16-17). There was increased resource utilization during WIA
      periods compared with the non-WIA periods for the following parameters: admission
      rate (24% [95% CI, 24-25%] versus 23% [23-23%]), ED LOS admitted (296 [95% CI,
      280-313] versus 271 [95% CI, 265-277]), ED LOS discharged (162 [95% CI, 156-168]
      versus 152 [95% CI, 150-154]), ED saturation time (1292 [95% CI, 689-1894] versus
      409 [95% CI, 209-609]) and LWBS (31 [95% CI, 19-42] versus 14 [95% CI, 12-15]).
      Although each WIA period was marked by an initial spike in patient volume, weekly
      census did not increase (1365 [95% CI, 1297-1433] during WIA versus 1297 [95% CI,
      1275-1320] during non-WIA). An association between WIA and greater ED resource
      demand was observed. A spike in census was observed at the onset of each WIA
      period. In addition, the flu index increased during WIA, suggesting the use of
      the ED as a site for syndromic surveillance of WIA onset.

PMID- 14655233
TI  - Sciatic nerve injuries associated with traumatic posterior hip dislocations.
AB  - This study was undertaken to test the hypothesis that patients transferred
      between hospitals with a dislocated hip have a greater incidence of sciatic nerve
      injury than patients who have their hip reduced at the first facility. One
      hundred six dislocated hips were included in this 12-year retrospective study.
      Sixty-nine hips were relocated at the first hospital and 36 patients were
      transferred with the hip still dislocated to LDS Hospital. There was a higher
      incidence of major sciatic nerve injury (complete sciatic or peroneal motor
      deficit) in patients transferred with the hip still dislocated (P =.0453). Time
      to relocation was significantly longer in patients with major motor nerve injury
      (P =.016). The presence of an associated fracture had no influence on sciatic
      nerve injury rates. The length of time a hip remains dislocated influences the
      incidence and severity of major sciatic nerve injury.

PMID- 14655232
TI  - Hospital admissions associated with nontraumatic dental emergencies in a Medicaid
      population.
AB  - Few studies have examined visits to hospital EDs and subsequent admission for the
      treatment of nontraumatic dental emergencies. The present study of Medicaid
      eligible adults was conducted to gain a better understanding of the magnitude of
      this problem. Data tapes describing adult Medicaid patients' hospital ED and
      admission claims were obtained from the Maryland Medicaid Management Information
      System. The database contained information on all claims made to Maryland
      Medicaid during the period February 16, 1991, to February 15, 1995. There was a
      total of 4326 dental-related ED claims, which resulted in 85 hospital admissions.
      Thus, approximately 2% of dental-related ED visits during the 4-year study period
      resulted in a hospital admission. The mean total cost for claims associated with
      hospital admissions was $5793 US dollars, whereas the minimum cost was $949 and
      the maximum was $43,524 US dollars. Although the frequency of hospital admissions
      associated with nontraumatic dental emergencies is not great, a hospital
      admission is among the most extreme consequences of failing to prevent or treat
      dental problems. Although some hospital admissions related to dental problems
      could be unavoidable, further studies are needed to better understand mechanisms
      for reducing the use of EDs for care best provided in community-based dental
      offices.

PMID- 14655234
TI  - Spontaneous coronary artery dissection causing acute coronary syndrome: an early
      diagnosis implies a good prognosis.
AB  - Spontaneous coronary artery dissection is an unusual cause of acute coronary
      syndrome. We describe a series of cases that with an early diagnosis and
      aggressive treatment, which includes percutaneous angioplasty with stent
      implantation and cardiac surgery, had a good outcome. The objective was to study
      the demographic characteristics, clinical settings, treatments, and inhospital
      course of patients with spontaneous coronary artery dissection. We studied a
      retrospective case series in 3 coronary care units in third-level university
      hospitals. The spontaneous coronary artery dissection diagnosis was made by
      coronary angiography. Seven cases of spontaneous coronary artery dissections were
      recorded. They were 5 women and 2 men. The age range was 28 to 64 years. Two of
      them took oral contraceptives and one case occurred in the postpartum period. An
      acute anterior wall myocardial infarction was the most frequent clinical
      presentation, occurring in 4 of the 7 cases. In fact, the left anterior
      descending artery was involved in 6 cases. An urgent coronary angiogram was
      performed in all cases. Definitive treatment included percutaneous angioplasty
      and stent implantation in 3 cases, coronary artery bypass surgery in 2 case, and
      cardiac transplantation in another case. One patient was treated medically. None
      of the patients died in the hospital. Spontaneous coronary artery dissection
      remains an unusual cause of acute coronary syndrome. It should be included in the
      differential diagnosis of acute myocardial infarction, especially when it affects
      young, healthy females. An early clinical suspicion and diagnosis with urgent
      coronary angiography and aggressive treatment that includes percutaneous
      angioplasty with stent implantation and cardiac surgery could improve the
      prognosis of these patients.

PMID- 14655235
TI  - Preferential distal radius fracture in right-handed individuals presenting to an
      ED.
AB  - The purpose of this study was to determine whether there is a lateralizing
      predisposition toward injury in right hand-dominant (RHD) individuals. The distal
      radius fracture was used as the injury for evaluation because it is easily
      defined and can be objectively documented by roentgenography. A prospective case
      series design was used to include consecutive RHD patients with a distal radius
      fracture. There were 86 women with an average age of 63.1 +/- 17.9 years and 41
      men with an average age of 44.0 +/- 17.6 years with a significant difference
      between ages (P <.01). Overall, there were 50 right and 77 left distal radius
      fractures, which was significantly different than a 50:50 split (P <.025).
      Stratification and logistic regression analysis revealed that age (dichotomized
      into age greater than 57 or other) and not gender was a significant factor in the
      determination of left versus right distal radius fracture. No interaction between
      age and gender was found. After adjustment for gender, the odds of developing a
      left compared with right distal radius fracture was 2.3-fold greater for the
      older compared with the younger age group (95% confidence interval, 1.0-5.2).
      Preliminary evidence suggests a lateralizing predisposition for left distal
      radius fractures in older compared with younger individuals who are RHD. If this
      data holds up, finding the etiology/mechanism of this predisposition might help
      in designing environments to minimize the impact of this injury pattern in the
      slightly older individual.

PMID- 14655236
TI  - Myoclonus associated with etomidate for ED procedural sedation and analgesia.
AB  - We report 3 cases of myoclonus associated with etomidate during ED procedural
      sedation and analgesia (PSA). EPs should be familiar with myoclonus associated
      with etomidate. Clinicians using this drug for PSA should be prepared to offer
      the brief period of support, and occasionally, respiratory assistance, required
      when etomidate-associated myoclonus is encountered.

PMID- 14655237
TI  - Diagnostic peritoneal lavage through an abdominal stab wound.
AB  - Diagnostic peritoneal lavage (DPL) is one of the most useful tools in the
      diagnosis of intraperitoneal injuries secondary to stab wounds. The lavage
      catheter is inserted into the peritoneal cavity through a surgical incision or a
      blind puncture. Complications related to the catheter insertion were previously
      reported in both techniques. We describe 2 cases in which the lavage catheter was
      inserted through the stab wound itself after local wound exploration clearly
      demonstrated violation of the peritoneum. We suggest that in anterior abdominal
      stab wounds, the DPL can be safely and effectively performed through the stab
      wound if penetration to the peritoneum is diagnosed.

PMID- 14655238
TI  - Rescuers' effect on active compression-decompression cardiopulmonary
      resuscitation (ACD-CPR) operating.
AB  - The purpose of this study is to consider the perceptions of rescuers of ACD
      operation and their anatomy characteristics are evaluated to yield a better
      understanding on operation of ACD. A prospective, descriptive study to evaluate
      professional providers received ACD training. A total of 39 emergency medical
      professional participated in this study. CPR is performed as both ACD and
      standard CPR on a manikin separately. 56.4% of the participants felt that the ACD
      device was not easy or was very difficult to use. The easy-to-use group had a
      greater height, shoulder to iliac crest distance, shoulder to knee distance, and
      forearm length. The taller rescuers operate ACD more easily. In addition, women
      might operate ACD more difficultly. Modifying the operation of ACD (such as by
      putting a blanket put under the rescuer's knee or using footstool) was
      recommended and seems reasonable. These issues should be addressed on training.

PMID- 14655239
TI  - Additional electrocardiographic leads in the ED chest pain patient: right
      ventricular and posterior leads.
AB  - In the evaluation of the patient with chest pain, the 12-lead electro cardiogram
      is a less-than-(ECG) perfect indicator of acute myocardial infarction (AMI),
      particularly when used early in the course of the acute ischemic event; this
      relative insensitivity for AMI results from many different issues, including a
      less-than-optimal imaging of certain areas of the heart. It has been suggested
      that the sensitivity of the 12-lead ECG can be improved if 3 additional body
      surface leads are used in selected individuals. Acute posterior (PMI) and right
      ventricular myocardial infarctions are likely to be underdiagnosed, because the
      standard lead placement of the 12-lead ECG does not allow these areas to be
      assessed directly. Additional leads frequently used include leads V(8) and V(9),
      which image the posterior wall of the left ventricle, and lead V(4R), which
      reflects the status of the right ventricle. The standard ECG coupled with these
      additional leads constitutes the 15-lead ECG, the most frequently used additional
      lead ECG in clinical practice. The use of the additional leads might not only
      confirm the presence of AMI, but also provide a more accurate reflection of the
      true extent of myocardial damage.

PMID- 14655240
TI  - Influence of electrode misplacement on the electrocardiographic signs of inferior
      myocardial ischemia.
AB  - Electrocardiographic (ECG) artifacts resulting from misplacements of electrodes
      are frequent, difficult to detect, and can become of clinical importance. We
      investigated 2 healthy volunteers and 3 patients with ECG signs of inferior
      myocardial scars. We exchanged the peripheral electrodes in a defined manner and
      investigated the resulting ECG for morphology and possible diagnostic errors. In
      the volunteers, ECG signs of inferior ischemia could be produced. In the patients
      with ischemic heart disease, normal ECG without signs of ischemia resulted by
      placing the electrode of the left leg to the left arm. The automatic ECG analyzer
      was not helpful in detecting artifacts by misplaced electrodes. A very low
      amplitude of the QRS complex in lead I, II, or III was pathognomonic for
      electrode misplacement in half of the cases. ECG artifacts must also be suspected
      when abnormal QRS- or P-axis occur or when QRS morphology does not match with the
      clinical presentation of the patient.

PMID- 14655241
TI  - Myocardial infarction resulting from nonatherosclerotic coronary artery diseases.
AB  - Myocardial infarction (MI) infrequently results from nonatherosclerotic coronary
      diseases such as coronary embolism, spasm, dissection, and arteritis. If these
      disorders are not considered in the differential diagnosis of MI, specific
      beneficial therapies would be overlooked. Because physicians see large number of
      patients with MI during their career, the likelihood that they will encounter
      patients with MI resulting from nonatherosclerotic diseases is high. Two cases
      are presented to highlight different etiologies and treatment approaches of
      nonatherosclerotic MI.

PMID- 14655242
TI  - Trauma: an annotated bibliography of the recent literature, 2002.

PMID- 14655243
TI  - Brugada syndrome.

PMID- 14655244
TI  - Undiagnosed lung cancer presenting with dysgeusia.

PMID- 14655245
TI  - Spontaneous intracranial hypotension.

PMID- 14655246
TI  - Length of stay predicts patient and family satisfaction with trauma center
      services.

PMID- 14655247
TI  - Patients' perception of the physician-patient relationship.

PMID- 14655253
TI  - Failed pilonidal surgery: new paradigm and new operation leading to cures.

PMID- 14655248
TI  - False-positive abdominal radiography in a body packer resulting from
      intraabdominal calcifications.

PMID- 14655254
TI  - The management of leaking rectal anastomoses by minimally invasive techniques.

PMID- 14655255
TI  - Immunohistochemical study of myofibroblasts in colorectal epithelial lesions.

PMID- 14655256
TI  - Utility of complete blood count and blood culture screening to diagnose neonatal
      sepsis in the asymptomatic at-risk newborn.

PMID- 14655257
TI  - Youngest pallbearer.

PMID- 14655258
TI  - Older and unemployed.

PMID- 14655259
TI  - Keeping kids comfortable.

PMID- 14655260
TI  - Will the use of insulin analogs improve glycemic control during adolescence?

PMID- 14655261
TI  - Insulin glargine improves hemoglobin A1c in children and adolescents with poorly
      controlled type 1 diabetes.
AB  - The pediatric diabetes team at the University of Minnesota made a clinical
      decision to switch patients with type 1 diabetes with a hemoglobin A1c level
      greater than 8.0% to insulin glargine in an effort to improve glycemic control.
      Retrospective chart analysis was performed on 37 patients 6 months after the
      switch to insulin glargine therapy. RESULTS: After 6 months, the average
      hemoglobin A1c level in the entire cohort dropped from 10.1 +/- 2.0 to 8.9 +/-
      1.6% (p = 0.001). Thirty patients responded with an average hemoglobin A1c drop
      of 1.7 +/- 1.5%, from 10.3 +/- 2.2 to 8.6 +/- 1.5% (p < 0.001). Seven patients
      did not respond to insulin glargine therapy, with an average hemoglobin A1c rise
      of 1.0 +/- 0.8% from a baseline of 9.5 +/- 1.0% to 10.4 +/- 1.4% (p = 0.01). The
      greatest response was seen in children with an A1c > 12.0%, who dropped their
      hemoglobin A1c by 3.5 +/- 1.9%. Compared with responders, non-responders had
      significantly less contact with the diabetes team in the form of clinic visits
      and telephone conversations both before and after initiation of glargine therapy.
      Sixty-two per cent of patients received insulin glargine at lunchtime, when
      injections could be supervised at school. Three episodes of severe hypoglycemia
      occurred after initiation of insulin glargine therapy. CONCLUSIONS: Insulin
      glargine substantially improved glycemic control in children and adolescents with
      poorly controlled type 1 diabetes. This response was most remarkable in those
      with a baseline hemoglobin A1c level > 12.0%, and may have been related to
      increased supervision of injections.

PMID- 14655262
TI  - Normal hepatic glycogen storage after fasting and feeding in children and
      adolescents with type 1 diabetes.
AB  - OBJECTIVE: Hypoglycemia is the most important acute complication in patients with
      type 1 diabetes. Liver glycogen is an important storage form of glucose and thus
      important for maintaining glucose homeostasis. To test the hypothesis whether
      abnormal storage of glycogen in the liver is contributing to the risk of
      hypoglycemia in type 1 diabetic children and adolescents, liver glycogen was
      measured. STUDY DESIGN: Hepatic glycogen concentrations were measured in 19 type
      1 diabetic children and adolescents as well as in 19 age-matched controls,
      following overnight fasting and 4 h after two standardized meals. Hepatic
      glycogen was assessed by natural abundance 13C nuclear magnetic resonance
      spectroscopy (MRS). RESULTS: Mean (+/- SEM) fasting hepatic glycogen
      concentrations measured in arbitrary units (au) were similar in type 1 diabetic
      subjects and controls (4.98 +/- 0.36 vs. 4.48 +/- 0.33 au; p = 0.31). Both groups
      presented with an increase in liver glycogen concentrations 4 h after the
      standardized meals (diabetic subjects 5.70 +/- 0.37 au, p = 0.01; controls 5.78
      +/- 0.47 au, p < 0.01). Hepatic glycogen accumulation after feeding was 19.1% in
      diabetic children and adolescents compared with 35.8% in controls, but this
      difference did not reach significance. CONCLUSION: In children and adolescents
      with moderately controlled type 1 diabetes, hepatic glycogen stores after fasting
      and feeding are comparable to those of matched controls.

PMID- 14655263
TI  - Ketoacidosis at onset of type 1 diabetes mellitus in children--frequency and
      clinical presentation.
AB  - BACKGROUND: Since 1987, patients with newly diagnosed diabetes mellitus type 1
      under 15 yr of age have been registered in Baden-Wuerttemberg (BW), Germany. AIM:
      Our aim was to describe the frequency and the clinical presentation of diabetic
      ketoacidosis (DKA) at onset of type 1 diabetes mellitus in children. METHODS: All
      31 pediatric departments in BW and one diabetes center participated in this
      study. Hospital records of 2121 children below 15 yr of age were examined
      retrospectively. DKA was defined as glucose > 250 mg/dL, pH < 7.30 or bicarbonate
      < 15 mmol/L and ketonuria. Statistical analysis was done after logarithmic
      transformation. RESULTS: 26.3% (n = 558) of all patients presented with DKA. The
      mean age of these patients was 7.9 yr. The frequency of DKA is higher in girls
      than in boys (28.9 vs. 23.8%; p = 0.0079). Those aged 0-4 yr suffered most
      frequently (p < 0.0001) from ketoacidosis (36.0%). The percentage of DKA in newly
      diagnosed cases was constant over 10 yr. 23.3% of all patients with DKA presented
      with an altered level of consciousness; 10.9% of these had clinical signs of
      coma. No deaths occurred. The proportion of ketoacidosis does not increase
      concurrently with the number of diabetes manifestations in winter. CONCLUSION:
      The proportion of DKA in children with newly diagnosed diabetes mellitus is
      significant. In particular, children < 5 yr and girls face an increased risk. DKA
      may be the result of a particularly aggressive subtype of diabetes.

PMID- 14655264
TI  - Cost-effectiveness of use of the GlucoWatch Biographer in children and
      adolescents with type 1 diabetes: a preliminary analysis based on a randomized
      controlled trial.
AB  - OBJECTIVE: To conduct a preliminary analysis of the cost-effectiveness of the use
      of the GlucoWatch Biographer in the management of type 1 diabetes in children and
      adolescents. METHODS: The computer model used to analyze the cost-effectiveness
      of intensive diabetes treatment in the Diabetes Control and Complications Trial
      (DCCT) was modified to simulate cohorts of patients who participated in a small
      clinical trial at one center comparing standard and Biographer-assisted standard
      care. The model is a Monte Carlo simulation model that simulates the lives of
      individual patients. Cohorts of 10,000 patients are simulated to accumulate
      statistics on average treatment costs and complications. Complication and
      treatment costs were updated to 2002 dollars. Future costs and benefits are
      discounted using a rate of 3%. The perspective of the analysis is from a single
      payer of health care costs. RESULTS: The model predicts that use of the
      Biographer, if sustained for the life of the cohort, would delay the development
      of the first serious diabetes complication by 4.1 yr. Treating 18 subjects would
      prevent one case of blindness and 1.4 cases of renal failure. The intervention
      costs $91,059/years-of-life (YOL), $61,326/quality-adjusted life-years (QALYs),
      and $9930/yr free of a major complication. If the biographer ceased to be
      effective after age 17, the cost per QALY would increase to $103,178/QALY gained.
      CONCLUSIONS: Preliminary analysis of the cost-effectiveness of use of the
      GlucoWatch Biographer in diabetes management is encouraging. Definitive analysis
      will require confirmation in other studies and populations.

PMID- 14655265
TI  - Genetic epidemiology of type 1 diabetes.
AB  - Family and twin studies indicate that a substantial fraction of susceptibility to
      type 1 diabetes is attributable to genetic factors. These and other epidemiologic
      studies also implicate environmental factors as important triggers. Although the
      specific environmental factors that contribute to immune-mediated diabetes remain
      unknown, several of the relevant genetic factors have been identified using two
      main approaches: genome-wide linkage analysis and candidate gene association
      studies. This article reviews the epidemiology of type 1 diabetes, the relative
      merits of linkage and association studies, and the results achieved so far using
      these two approaches. Prospects for the future of type 1 diabetes genetics
      research are considered.

PMID- 14655266
TI  - Leptin: obesity, diabetes and other peripheral effects--a review.
AB  - There is an increasing epidemic of obesity in the Western and developing world
      that has not spared children and, hence, is of great concern. Obesity presents
      numerous physiological and psychosocial problems for the child. Childhood obesity
      not only increases the risk of obesity in adulthood, it is associated with type 2
      diabetes mellitus; is the leading cause of pediatric hypertension; increases the
      risk of coronary heart disease; and increases stress on the weight-bearing
      joints. Social and psychological problems are also significant consequences of
      obesity in children, with lowering of self-esteem and its effects on
      relationships with peers. Obesity is clearly associated with increased levels of
      the recently discovered hormone, leptin. Leptin, secreted from adipocytes, is
      involved in the regulation of food intake, energy expenditure, and energy balance
      in humans. This review focuses on the hormone, leptin, in an effort to document
      some of its many local and systemic effects on the body and, specifically, its
      potential role in obesity-induced diabetes.

PMID- 14655267
TI  - Coexistence of type 1 and type 2 diabetes mellitus: "double" diabetes?

PMID- 14655268
TI  - Measuring insulin resistance: a task worth doing. But how?

PMID- 14655269
TI  - Evaluation of HOMA and QUICKI as measures of insulin sensitivity in prepubertal
      children.
AB  - BACKGROUND: Simple fasting sample methods to measure insulin sensitivity (SI)
      such as homeostasis model assessment (HOMA) and quantitative insulin-sensitivity
      check index (QUICKI) have been widely promoted in adult studies but have not been
      formally evaluated in children. The aim of this study was to compare HOMA and
      QUICKI to the minimal model as measures of SI in prepubertal children. METHOD:
      The study population consisted of twins (n = 44), premature (n = 17), small for
      gestational age (SGA) (15), and normal (n = 3) prepubertal children. The insulin
      sensitivity index derived by the minimal model (SIMM) was calculated by the
      minimal model with plasma glucose and insulin data from a 90-min frequently
      sampled intravenous glucose test with tolbutamide. The HOMA resistance index
      (RHOMA) and QUICKI were calculated from fasting plasma glucose and insulin
      values. RESULTS: The correlation between RHOMA and SIMM (r = -0.4, p < 0.001) was
      no better than that between fasting insulin and SIMM (r = -0.4, p < 0.001).
      QUICKI was poorly correlated with SIMM (r = 0.2, p = 0.02). The correlation
      between SIMM and RHOMA is largely confined to low SI values (< 10 x 10(-4)/min
      microU/mL.) In seven SGA subjects, the introduction of growth hormone treatment
      led to an expected fall in SIMM by 8.2 +/- 2.8 x 10(-4)/min microU/mL (p = 0.02)
      that was not detected by either RHOMA (p = 0.1) or QUICKI (p = 0.2). Similarly,
      SIMM values were lower in obese (n = 9) compared to non-obese subjects (p =
      0.04); however, no difference was found between these two groups with either
      RHOMA (p = 0.21) or QUICKI (p = 0.8). CONCLUSION: As measures of SI in
      prepubertal children, RHOMA is no better than fasting insulin and QUICKI, a poor
      measure. Neither RHOMA nor QUICKI was able to detect changes in SI induced by
      either obesity or growth hormone therapy.

PMID- 14655270
TI  - Intramyocellular lipid, adiposity, and muscle oxygen supply in prepubertal type 1
      diabetes.
AB  - BACKGROUND: In the non-diabetic population, intramyocellular lipid (IMCL)
      accumulation is associated with obesity and poor muscle oxygen supply. IMCL
      levels are increased in type 1 diabetes, but their significance is less clear.
      METHODS: We studied a group of 16 prepubertal boys (age 6.4-9.9 yr) with type 1
      diabetes and a range of glycemic control [hemoglobin A1c (HbA1c) 6.4-10.2%].
      Children's adiposity was assessed by anthropometry, muscle oxygen supply by near
      infrared spectroscopy (NIRS), abdominal and IMCL content by magnetic resonance
      imaging (MRI), and magnetic resonance spectroscopy (MRS). RESULTS: IMCL content
      did not associate with muscle reoxygenation rate, abdominal adiposity, duration
      of diabetes, or recent glycemic control. Muscle reoxygenation rate correlated
      with percentage body fatness (r2 = 0.46, p = 0.004), visceral (r2 = 0.45, p =
      0.007) and abdominal subcutaneous fat volume (r2 = 0.63, p = 0.0004), and dietary
      fat intake (r2 = 0.27, p = 0.03) but not with the duration of diabetes nor HbA1c.
      HbA1c was significantly related to dietary fat intake only (r2 = 0.28, p = 0.03).
      CONCLUSION: While causality cannot be inferred, interventions aimed at improving
      muscle oxygen supply, or preventing its deterioration, might reduce the
      development of adiposity in children with type 1 diabetes.

PMID- 14655271
TI  - The impact of diabetes on health-related quality of life in children and
      adolescents.

PMID- 14655272
TI  - Effectiveness of a rural pediatric diabetes management program.
AB  - BACKGROUND: Children with type 1 diabetes living in rural areas may have limited
      access to specialty diabetes care compared to children living in urban areas. To
      address this issue, providers have developed outreach services in which
      specialists travel periodically to rural communities. OBJECTIVE: To determine
      whether the care of children with type 1 diabetes treated by pediatric
      endocrinologists in a rural outpatient clinic is comparable to the care of
      children treated in an urban medical center by the same diabetes team. METHODS:
      We carried out a retrospective cohort study comparing the number of patient
      visits with physicians, behavioral specialists, and dietitians and the frequency
      of hemoglobin A1c (HbA1c) measurements over a 12-month period treated in a rural
      clinic with a matched group treated in an urban children's hospital clinic.
      RESULTS: We found that urban patients (n = 38) were more likely to complete four
      visits per year compared to a matched group (n = 19) at the rural clinic (55.3%
      vs. 15.8%; p < 0.004), were significantly more likely than those in the rural
      clinic to have had four HbA1c measurements per year (55.3% vs. 21.1%; p < 0.014),
      and more likely to have had an assessment by a behavioral specialist (31.6% vs.
      0%). Children at the rural clinic site were more likely to have had a visit with
      a nutritionist during the year (89.5% vs. 36.8%; p < 0.005). CONCLUSION: We
      conclude that diabetes care provided using a rural outreach model closely
      approximates, but does not entirely duplicate, care provided in the urban
      setting.

PMID- 14655273
TI  - Hypoglycemia in children with type 1 diabetes: current issues and controversies.
AB  - Hypoglycemia is a common complication of insulin therapy, particularly in the
      young. For children and adolescents with diabetes, the risk of hypoglycemia may
      not only prevent optimal glycemic control but can also add significantly to the
      psychosocial burden of the disease. Recently, surveys employing prospective
      monitoring techniques have allowed more precise information to be gained about
      rates of hypoglycemia, its clinical associations, and the impact of new therapies
      and technologies. A number of reports have estimated rates of hypoglycemic comas
      and convulsions to be approximately 20 events per 100 patient years in children
      on current conventional therapy. There is evidence that the introduction of new
      analog short- and longer-acting insulins and the more widespread use of
      continuous subcutaneous infusion therapies may allow improvements in glycemic
      control to occur without the usual increased rate of severe hypoglycemic
      episodes. The use of glucose sensor technology has brought into focus the
      widespread occurrence of asymptomatic hypoglycemia. Asymptomatic hypoglycemia has
      long been recognized, particularly at night, when the combination of excessive
      insulin action and suppressed counter-regulatory hormone responses put children
      at special risk of hypoglycemia. Hypoglycemia unawareness is common in the young
      and is associated with an increased risk of severe hypoglycemia. Whether episodes
      of severe hypoglycemia have long-term consequences is controversial. Early
      studies suggesting that the developing brain is sensitive to permanent
      neurological damage as a result of hypoglycemia have not been confirmed in more
      recent reports. Many studies have not found convincing evidence of neurological
      sequelae of the hypoglycemic events that are an inevitable complication of
      insulin therapy. The question, however, remains under active investigation.
      Continued prospective monitoring of hypoglycemia rates and consequences has
      become an essential component of diabetes management.

PMID- 14655274
TI  - Life-threatening autoimmunity with diabetes: management with an insulin pump.
AB  - A 2-yr-old boy presented initially with type 1 diabetes (T1D). Over the next 9
      yrs, he developed multiple autoimmune conditions including Evans' syndrome,
      alopecia, and autoimmune bowel disease. Autoimmune polyendocrinopathy,
      candidiasis, ectodermal dystrophy (APECED) syndrome was considered, but no
      mutations were found in the autoimmune regulator-1 (AIRE-1) gene, making this
      diagnosis unlikely, and he did not fulfill the clinical criteria for immune
      dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. We
      describe the challenges created by the combination of these diseases and how
      introduction of insulin pump therapy revolutionized his care.

PMID- 14655275
TI  - [Biological weapons--an old menace in new circumstances].
AB  - Biological weapons were conceived for years by the world community only as a
      potential evil. A fundamental change of opinions regarding their real menace
      occurred only after the premeditated criminal attack on the USA on September 11,
      2001. It was logical that publicists for mall types of media demanded from
      representatives of the state administration of the Czech Republic information how
      out country is prepared for this type of danger. Their reactions were hesitant
      and in a way reflect a certain chaos associated with the reorganization of the
      army and at the same time unpreparedness of civil defence. To a certain extent
      all this can be conceived as the consequence of the fundamental transformation of
      our society and thus it may be excused to a certain extent. Nevertheless it is
      obvious that not even the most advanced countries are quite clear as regards
      defence against the horror of biological weapons. Evidence to this effect is the
      following document, devoted to the problem in the USA, major parts of which we
      reproduce from the prestigious periodical The England Journal of Medicine.

PMID- 14655276
TI  - [Nerve paralytic agents--the greatest threat for mass poisoning during chemical
      warfare or terrorist attacks].
AB  - Since thirties of the previous the highly toxic organophosphorus compound called
      nerve agents have been considered the most dangerous chemical warfare agents that
      could be misused in local and world wars or during terrorist attacks. Beside the
      historical introduction, the article summarizes contemporary knowledge on the
      mechanism of toxicity of these agents, on the possibilities of diagnosis,
      prophylaxis and treatment. The possibility of using similar methods of diagnosis,
      prophylaxis and treatment for acute poisoning with organophosphorus insecticides
      is also mentioned.

PMID- 14655277
TI  - [Glanders--an eradicable disease--or a threat?].
AB  - Glanders (malleus), attacking equids and transmissible to humans, does not occur
      in our geographical area any more, but world-wide eradication has not yet been
      achieved. Cases of glanders have been reported from India, Iraq, Mongolia and
      China and in 2001 also from South America. The disease is caused by Burkholderia
      mallei (earlied known as Bacillus, Pfeiferella, Loefflerella, Malleomyces,
      Actinobacillus, or Pseudomonas mallei). The continual interest of microbiologists
      in the causative agents indicates that glanders cannot be regarded as a closed
      historic episode. Occupational infections of laboratory personnel occurred during
      World War II and the years thereafter and the last accident was reported in May
      2000. Topical problems of glanders include the development of a vaccine and
      antibiotic therapy tested in experimentally infected subjects.

PMID- 14655278
TI  - [Lysosomal sphingomyelinase deficiency: spectrum of phenotypes in Czech and
      Slovak patients].
AB  - BACKGROUND: We present a series of 25 patients (from 21 families) with deficiency
      of lysosomal sphingomyelinase (acid sphingomyelinase, ASM), diagnosed during the
      last 30 years. METHODS AND RESULTS: Diagnosis was established by finding specific
      sphingomyelin storage pattern in bone marrow histiocytes and in some bioptical
      and postmortem tissues (presence of sphingomyelin liquid crystals) and finally by
      proving ASM deficiency in white blood cells and in cultured fibroblasts. Range of
      clinical manifestations of our patients notably exceeded the the known main (A,B)
      phenotypes described so far. In the group of type A patients (clinically overt
      neurovisceral symptomatology) there was significant tendency to prolonged course.
      Classical fulminant course with death between 5 to 45 months of age was seen only
      in a subgroup of 5 patients. In other type A patients (n = 8) the course was
      prolonged attaining 5 years of age, the end of the first (8, and 9 years), second
      (14, 17 years), third (22 years), fourth (32 years) and fifth decades (41 years).
      Three of these patients (aged 5, 22 and 41 years) are living. The series of
      patients with dominant visceral involvement (n = 12) consisted of three
      phenotypically different subgroups. One with chronic purely visceral affection
      and prolonged course (n = 4) corresponding to the classical type B, the second
      with chronic course and largely subclinical neurological affection (n = 4) and
      the third with accelerated fatal visceral affection (death in age range 31 months
      9 years) without (n = 1) or with clinically minor signs of brain damage (n = 3).
      CONCLUSIONS: Study of the presented series of ASM deficient patients disclosed
      remarkable phenotypical variability. Two main factors seem to be responsible.
      Variability in the storage intensity in the two main tissue compartments
      (neuronal and visceral), and the absence of proportionality in their affection in
      some instances. The described phenotype variability enlarges significantly the
      known spectrum of phenotypes in ASM deficiency.

PMID- 14655279
TI  - [The comet assay: principles of the method and clinical utilization].
AB  - BACKGROUND: Single cell gel electrophoresis or comet assay is used at present in
      the world to study of DNA damage, DNA repair and apoptosis. The aim of the work
      is to introduce the principle of comet assay to the medical community and to give
      a basic survey of its possible clinical applications. The article includes our
      first experience with this method in detection of apoptosis in bone marrow cells
      of patients with myelodysplastic syndrome (MDS). METHODS AND RESULTS: The whole
      bone marrow aspirates from 6 patients with MDS and 7 control persons were
      processed by alkaline version of comet assay and the degree of DNA fragmentation
      in individual cells was quantified using Image Analysis System. In comparison
      with controls, the patients with diagnosis RA and RARS exhibited in bone marrow
      significantly elevated number of cells with high level of DNA breaks, reflecting
      most probably the apoptotic cleavage of DNA. In contrast, the patient in
      proliferative stage of the disease (MDS-CMML-->AML) exhibited decreased frequency
      of apoptotic cells, well below the control level. CONCLUSION: Our results
      correspond with the data published on the occurrence of apoptosis in particular
      types of MDS. Comet assay represents a simple and cheap technique, applicable in
      clinical hematology to specify the diagnosis, to monitor the disease progress and
      efficacy of therapy not only in patients with MDS but also in other diseases
      resulting from an imbalance between proliferation and apoptosis.

PMID- 14655280
TI  - [Effect of sideropenic anemia and its therapy on serum levels of leptin].
AB  - BACKGROUND: Leptin is a protein hormone produced predominantly by adipocytes. Its
      major role in human body is probably to regulate the food intake through the
      hypothalamic satiety center. One of the peripheral effects of leptin, which was
      studied mainly in vitro so far, is its stimulating effect on the haematopoietic
      stem cells. The information concerning the changes of serum leptin levels in
      various haematological diseases is very limited. The aim of our study was to
      explore changes of serum leptin levels in patients with sideropenic anaemia at
      the time of diagnosis and in the various phases of their treatment. METHODS AND
      RESULTS: 18 patients with untreated sideropenic anaemia (SA) and 20 healthy age,
      gender and weight-matched control subjects were included into the study. The
      blood testing in SA patients was performed before anaemia treatment, at the time
      of maximal increase of reticulocytes and after haemoglobin levels normalisation.
      Blood count, serum leptin, erythropoietin (EPO) and transpherine receptor (TfR)
      levels were estimated in all samples. Basal serum leptin levels in SA patients
      did not differ significantly from those of control subjects (13.9 +/- 14.6 SD vs
      10.4 +/- 8.8 SD ng.ml-1). Treatment anaemia of did not significantly affect the
      serum leptin levels in SA patients (13.9 +/- 14.6 SD vs 12.9 +/- 12.6 SD vs 12.8
      +/- 15.1 SD ng-ml-1). Serum EPO and TfR levels in SA patients were higher before
      the start of treatment and decreased significantly after the anaemia recovery. In
      both groups serum leptin levels correlated positively with body mass index. No
      unambiguous statistically significant relationships between serum leptin levels
      and blood count parameters or serum EPO and TfR levels were found in any of the
      groups studied. CONCLUSION: Neither the changes of red blood cell count during
      the sideropenic anemia treatment nor the increased erythropoiesis affect
      significantly serum leptin levels.

PMID- 14655281
TI  - [Role of aspartic acid at position 57 of the HLA-DQ beta chain in sporadic and
      familial forms of selective IgA deficiency].
AB  - BACKGROUND: Selective IgA deficiency (IgAD) is the most frequent primary
      immunodeficiency in Caucasians. A protective effect of an aspartic acid residue
      at position 57 of the DQ beta chain against IgAD has been repeatedly described.
      The aim of our study was to determine, whether the genetic effect of non-aspartic
      acids (non-Asp) at position 57 of the DQ beta chain is different in familial and
      non-familial forms of IgAD. METHODS AND RESULTS: Codon 57 genotyping was
      performed in 59 patients with sporadic from in 28 patients with familial forms of
      IgAD, and in 162 control persons. Significantly increased occurrence of the non
      Asp residues at position 57 in IgAD patients compared to control persons was
      found, but there was no difference between familial and sporadic forms of IgAD.
      The association was not proved in six IgAD patients who were relatives of CVID
      patients. CONCLUSION: The protective effect of non-aspartic acid at position 57
      of the DQ beta chain is present in both sporadic and familial form of IgAD. This
      effect was not observed in IgAD relatives of CVID persons showing that a genetic
      background of this form might be different than in other forms of IgAD.

PMID- 14655282
TI  - [The truth about devitalization].

PMID- 14655283
TI  - [Enlarged ovary in a mare: review of the literature and a case report].
AB  - Mares regularly have an enlarged ovary. The main causes are haematomas,
      anovulatory follicles, abscesses, and neoplasia. The granulosa-theca-cell tumour
      is by far the most common neoplasia of the ovary (about 97%) and accounts for
      2.5% of all equine tumours. In this article the differential diagnosis of an
      enlarged ovary and the background of granulosa-theca cell tumours are reviewed. A
      case is described of a mare with a very large granulosa-theca cell tumour in the
      left ovary, which was discovered 1 month after delivery of a healthy foal. This
      case is special not only because the tumour was enormous (diameter 60 cm) but
      also because the contralateral ovary was functional and there were no behavioural
      changes. The fact that a haematoma had been found 2 years earlier made the
      diagnosis even more difficult.

PMID- 14655284
TI  - [Mystery and recovery].

PMID- 14655285
TI  - [Decision of the Veterinary Association with consequences: registration of vital
      signs during anesthetic recovery must become standard].

PMID- 14655286
TI  - [Quality warranty of veterinary drugs. Not a separate certificate, but a "life
      long' quality assurance system].

PMID- 14655287
TI  - [Museum veterinary medicine: guard of veterinary medicine history].

PMID- 14655288
TI  - [Misleading clinical experience].

PMID- 14655289
TI  - [NHZ insurance company?].

PMID- 14655290
TI  - [Severe chronic obstructive pulmonary disease in young women who smoke].
AB  - Chronic obstructive pulmonary disease (COPD) was diagnosed in three women aged
      39, 41 and 41 years who were all heavy smokers. They presented with symptoms of
      dyspnoea. At the time of diagnosis they already had advanced pulmonary emphysema
      and signs of systemic impairment. At the last follow-up one woman had a very
      limited range of action, the second was awaiting a lung transplant after several
      periods of hospitalization, and the third had died. Nowadays pneumologists are
      increasingly encountering severe COPD in young female patients. Increased tobacco
      consumption in women has run parallel to the rising mortality rates from COPD in
      females over the last decades. Cigarette smoking is probably associated with a
      higher risk of obstructive lung disease in women than in men. Moreover women with
      COPD maintain exercise capacity longer than men with similar degrees of airway
      obstruction, leading to a risk of them waiting too long before seeking medical
      help. Actions aimed at discouraging smoking especially in adolescence are without
      doubt the intervention of choice for prevention of this highly disabling disease.

PMID- 14655291
TI  - [Treatment of patients with Wegener's granulomatosis or ANCA-associated
      vasculitis].
AB  - Standard therapy of Wegener's granulomatosis is prednisolone in combination with
      cyclophosphamide. Cyclophosphamide is continued for 15-18 months after diagnosis.
      During therapy 26% of the patients have severe or life-threatening side effects,
      mostly infections. Furthermore, there are multiple long-term side effects such as
      an increased incidence of malignancies, especially bladder carcinoma. During the
      last 10 years the European vasculitis study group (www.vasculitis.org) organized
      several randomized clinical trials to determine optimal treatment. Recently, it
      was demonstrated in one of these trials that in patients with generalized ANCA
      associated vasculitis (vasculitis associated with antineutrophil cytoplasmic
      autoantibodies) withdrawal of cyclophosphamide and substitution by azathioprine
      after remission did not increase the rate of relapse and was safe. Wegner's
      granulomatosis is not a fatal disease anymore. Sometimes, however, patients lose
      their job. Fortunately, this occurs only in a small percentage of patients.

PMID- 14655292
TI  - [Barrett's esophagus: new developments in endoscopic surveillance].
AB  - The current surveillance strategies for patients with a Barrett's oesophagus are
      hampered by the poor endoscopic visibility of early neoplastic lesions, the
      sampling error of random biopsies, the subjectivity of the histological
      evaluation, and the low incidence of carcinoma. New endoscopic techniques are
      available for a more reliable evaluation of a Barrett's oesophagus: high
      resolution endoscopy, chromoendoscopy, fluorescence endoscopy and optical
      coherence tomography. The use of molecular markers will probably lead to a better
      risk stratification of patients. Detection of aneuploid cell populations and
      assessment of an increase of the number of cells in the S- and G2-phase are
      possible with DNA flow cytometry; flow cytometric abnormalities may be a more
      reliable predictor of carcinoma than histological assessment. A combined approach
      with the new endoscopic techniques and molecular markers may lead to a more
      efficient and cost-effective surveillance programme.

PMID- 14655293
TI  - [Barrett's esophagus: endoscopic treatment of high-grade dysplasia and early
      cancer].
AB  - In a Barrett's oesophagus without dysplasia, endoscopic control every 3-5 years
      is sufficient. If low-grade dysplasia is encountered in the surveillance
      biopsies, then endoscopy should be repeated within 3-6 months and yearly
      thereafter if the low-grade dysplasia persists. Antacid medication must be
      prescribed in cases with extensive inflammation. The endoscopic treatment of
      patients with high-grade dysplasia and/or early cancer of the mucosa in a
      Barrett's oesophagus (tissue ablation and/or mucosa resection) seems a promising
      alternative to surgery in view of the combination of effectiveness, limited
      invasiveness compared to surgical resection, and the preservation of a functional
      oesophagus. Data from long-term follow-up are still limited. Strict endoscopic
      surveillance will probably detect metachronic abnormalities in an early and still
      curable stage, creating a new opportunity for endoscopic treatment.

PMID- 14655294
TI  - [Pregnancy and chronic hypertension: risks and policy].
AB  - Chronic hypertension occurs in 5% of pregnancies and can threaten the life of the
      mother and the fetus. Chronic hypertension should be evaluated before pregnancy;
      special attention should be paid to the existence of organ damage and the
      presence of an acceptable incentive for treatment. The risk of complications of
      chronic hypertension in pregnancy should be discussed with the couple before
      pregnancy.

PMID- 14655295
TI  - [Diagnostic image (165). A woman with an inguinal mass. Lymphangitis
      carcinomatosis spread to the skin by metastases of an ovarian carcinoma].
AB  - In a 57-year-old woman ovarian cancer spread lymphogenically to the groin and
      suprapubic skin.

PMID- 14655296
TI  - [Possibilities for anonymous follow-up studies of patients in Dutch national
      medical registrations using the Municipal Population Register: a pilot study].
AB  - OBJECTIVE: To examine the feasibility of using information from the Dutch
      Municipal Population Register (Dutch acronym: GBA) to anonymously track groups of
      patients. DESIGN: Exploratory. METHOD: Using a random sample from the Dutch
      National Medical Register (Dutch acronym: LMR), hospital admission with discharge
      in January 1996, it was determined to what extent the admission records could be
      linked to the GBA. The following variables were used in the linking process: date
      of birth, gender and the numerical part (4 digits) of the postal code. Once a
      record had been linked to a single record in the GBA, the pattern of moving and
      mortality over the next two years was investigated. RESULTS: Of the 124,598
      different hospitalisation records in the LMR cohort, 84% could be linked with a
      single record in the GBA. In 11% of the patients no unique link was possible: one
      hospital record could be linked to several records in the GBA. No matching record
      could be found for 5% of the patients; some of these were foreign citizens
      resident in the Netherlands. Two years after discharge, the cumulative mortality
      was 44% for cancer patients, 28% for patients with acute myocardial infarction,
      57% for patients with heart failure and 20% for patients with respiratory
      diseases. Eleven percent of the patients moved within the two-year period
      following discharge. This would have caused a considerable bias in the
      aforementioned mortality rates, if the patients' migration had meant that they
      could no longer be followed. CONCLUSION: The introduction of the GBA has
      significantly increased the possibilities for following patients within and
      between registries. A prerequisite for this is a unique and correct
      identification of an individual within the GBA.

PMID- 14655297
TI  - [Endovascular treatment of 4 patients with a traumatic rupture of the thoracic
      aorta].
AB  - OBJECTIVE: To present our initial results with the endovascular treatment of
      traumatic rupture of the thoracic aorta. DESIGN: Retrospective. METHOD: Between
      April and October, 2002, 4 men between the ages of 22 and 46 were treated
      endovascularly for a traumatic rupture of the thoracic aorta. The diagnosis
      'rupture of the thoracic aorta' was made on the basis of CT-angiography in all
      cases. In the first case, a thoracic Gore TAG-endoprosthesis (Gore & Associates;
      Den Bosch) was used, and in 3 cases a Talent-endoprosthesis (Medtronic AVG;
      Heerlen). RESULTS: There was an average of 2.5 days (limits: 0-5 days) between
      admission and the placement of the endoprosthesis. There was one intra-operative
      complication in the form of a dissection of the right femoral artery when the
      endoprosthesis was inserted. In 3 cases, the left subclavian artery was occluded
      by the prosthesis. This had no negative consequences for the patients during the
      follow-up period (limits: 4-12 months). The CT-angiogram taken 3 months after the
      operation consistently showed a good position of the endoprosthesis with no signs
      of leakage. CONCLUSION: For a limited follow-up period, the endovascular
      treatment of a traumatic rupture of the thoracic aorta has been shown to be safe
      and effective. The long term results must be awaited.

PMID- 14655298
TI  - [A patient with Wegener's granulomatosis who worked in a foundry: a case for a
      causal association with silicon dioxide].
AB  - The diagnosis Wegener's granulomatosis was made in a 42-year-old man.
      Occupational history revealed prolonged exposure to large amounts of silicon
      dioxide in dust during work in a foundry. The illness was stabilized with
      immunosuppressive treatment, but after one year the patient developed aseptic
      necrosis in both hips, which ultimately led to essential total hip arthroplasty
      on the left side. The patient was unable to work since the diagnosis. Similar
      case reports have been described, as well as a limited number of case-control
      studies. These indicate an association between Wegener's granulomatosis and
      exposure to silicon. There is growing evidence for a causal role of silicon
      dioxide in the pathogenesis of auto-immune disease.

PMID- 14655299
TI  - [Causes of otalgia from outside the ear].

PMID- 14655300
TI  - [Causes of otalgia from outside the ear].

PMID- 14655301
TI  - [Causes of otalgia from outside the ear].

PMID- 14655302
TI  - [Causes of otalgia from outside the ear].

PMID- 14655303
TI  - [The prioritization of genetic screening with primary haemochromatosis as an
      example].

PMID- 14655304
TI  - [Mycobacterium haemophilum as the cause of lymphadenitis in the neck in an
      otherwise healthy boy].

PMID- 14655305
TI  - [Estimate of the number of new patients with type 2 diabetes mellitus in the
      Netherlands: at least 65,000 per year in the age group of 50 years and above].

PMID- 14655306
TI  - Ablation of atrial fibrillation in mitral valve disease patients: five year
      follow-up after percutaneous pulmonary vein isolation and mitral balloon
      valvuloplasty.
AB  - BACKGROUND: The association between atrial fibrillation (AF) and mitral valve
      disease is frequent. Isolation of the pulmonary veins by radiofrequency energy
      applications performed intraoperatively has been proposed for patients with AF in
      whom mitral valve surgery has been indicated. Balloon mitral valvuloplasty is
      currently the preferred procedure for patients with mitral stenosis and a
      favorable valve anatomy. AIM: To evaluate the short- and long-term results of
      percutaneous pulmonary vein isolation for the treatment of AF in patients with
      mitral stenosis undergoing balloon mitral valvuloplasty. METHODS: Five patients
      (four male and one female, age 43 +/- 4 years) underwent balloon mitral
      valvuloplasty concomitant with pulmonary vein isolation between August 1996 and
      February 1997. These patients had permanent AF, diagnosed 31 +/- 12 months
      previously; their mitral valve area was 1.0 +/- 0.25 cm2 and their left atria
      measured 54 +/- 5 mm. Balloon mitral valvuloplasty was performed via a
      transseptal approach, and then four ablation lines were created in the left
      atrial posterior wall to encircle all four pulmonary veins. Radiofrequency
      applications lasted 45 seconds each, and aimed at a maximum preset temperature of
      65 degrees C. Electrical cardioversion was performed at the end of the procedure.
      RESULTS: Mitral valve area increased 1.0 +/- 0.3 cm2 after valvuloplasty. The
      number of radiofrequency applications per patient was 37 +/- 3, and the average
      duration of the entire treatment was 131 +/- 28 minutes. Fluoroscopy time
      averaged 32 +/- 12 minutes. All patients were discharged in sinus rhythm, and
      mitral flow Doppler evaluation at one month showed a biphasic pattern in all
      cases, with the A wave measuring 70 +/- 15 cm/sec. Three patients maintained
      sinus rhythm at five-year follow-up. Of these patients, one had developed a left
      atrial flutter at four-year follow-up and underwent ablation. The remaining two
      patients presented AF at five year follow-up. CONCLUSIONS: Percutaneous isolation
      of the pulmonary veins concomitant with balloon mitral valvuloplasty had
      suppressed AF in 60% of patients by five-year follow-up.

PMID- 14655307
TI  - Coronary heart disease risk: the results of population screening by the Central
      Region Branch of the Portuguese Heart Foundation.
AB  - OBJECTIVE: To assess the ten-year risk of coronary heart disease according to the
      1998 Task Force Report. MATERIAL AND METHODS: 1013 adults, aged between 30 and 79
      years, were studied by trained paramedics, using a pre-determined routine
      technique. Prevalences: occasional capillary glycemia > 126 mg/dl in 11.2%,
      occasional capillary hypercholesterolemia > 190 mg/dl in 46.7%, arterial systolic
      hypertension in 37.3% and smoking habit in 18.2%. About 27.5% of the total were
      taking cardiovascular medication. There was a high or very high risk for coronary
      heart disease in 6.8% of the population, male 10.4% and female 3.8%. CONCLUSIONS:
      We found that the prevalence of high and very high risk for coronary heart
      disease is about 6.8%, being higher in men. Risk increases with age, the most
      prevalent being moderate risk, once again affecting mostly males.

PMID- 14655308
TI  - Long-term clinical impact of coronary-collateral vessels after acute myocardial
      infarction.
AB  - BACKGROUND: The positive impact of coronary collateral vessels in the acute phase
      of myocardial infarction (AMI) is already well established. However, their impact
      on longterm clinical outcome of these patients is still unclear. AIM: To study
      the impact of the presence of well established coronary collateral vessels on
      long-term clinical outcome of post-AMI patients. POPULATION AND METHODS: We
      analyzed the clinical evolution (mean follow-up time of 15.66.8 months) of 70
      patients who underwent coronary angiography shortly after AMI. According to the
      angiogram, the patients were divided into 2 groups: those with well developed
      coronary collateral vessels (n = 35) and those who did not show developed
      collateral circulation (n = 35). RESULTS: Both groups had similar baseline
      characteristics (regarding demography, coronary artery disease risk factors and
      predischarge evolution). The group with collaterals had more severe coronary
      disease compared with the group without collaterals (2.31 +/- 0.61 vs. 1.57 +/-
      0.7; p = 0.00001). Moreover, this group more frequently showed significant
      lesions on the left anterior descending artery (83% vs. 74%; p = NS), left
      circumflex (71% vs. 43%; p = 0.02) and right coronary arteries (74% vs. 40%; p =
      0.003). Primary percutaneous coronary intervention was more often performed in
      patients without coronary collateral vessels (58% vs. 30%; p = 0.02). Left
      ventricular function was similar in both groups. During follow-up, both groups
      underwent similar levels of revascularization by percutaneous coronary
      intervention and/or coronary artery bypass graft (70% vs. 76%; p = NS). Despite
      these characteristics, the group with collaterals showed a significantly better
      clinical outcome, with fewer events (combined endpoint of unstable angina, non
      fatal AMI, heart failure and death) after hospital discharge (40% vs. 69%; p =
      0.02) and a lower CCS functional class at the end of follow-up (1.26 +/- 0.63 vs.
      1.730.71; p = 0.03). CONCLUSION: After acute myocardial infarction, the presence
      of collateral vessels is associated with a better long-term clinical outcome.

PMID- 14655309
TI  - Safety evaluation of the use of femural percutaneous closure systems with
      simultaneous use of abciximab.
AB  - INTRODUCTION: The growing use of abciximab during coronary angioplasty, with 12
      hours of intravenous perfusion, prolongs hospital stay and increases the risk of
      hemorrhage after sheath removal at the puncture site. Femoral percutaneous
      closure devices can reduce immobilization time, but their safety in the presence
      of abciximab in respect to hemorrhage has not been clearly determined.
      OBJECTIVES: To evaluate the safety and efficacy of the Perclose system in
      patients undergoing angioplasty with abciximab. POPULATION AND METHODS: The
      Perclose system was used in 79 patients undergoing angioplasty, with abciximab in
      31 patients (58.6 +/- 12.2 years, 90% male, p = NS)--Group 1, and 48 pts without
      abciximab (61.8 +/- 10.9 years, 79% male, p = NS)--Group 2. We compared heparin
      dose, sheath diameters, primary success rate, coronary care unit admissions and
      minor and major complications. One patient was previously anticoagulated with
      warfarin and all the others were on oral antiplatelet therapy before and after
      angioplasty. RESULTS: Primary success with the use of the Perclose system was
      78%. We found no significant statistical differences between groups in respect to
      the presence of diabetes, sheath diameter or referral for intervention. Heparin
      dosage was slightly higher in group 2 (p = 0.09) and ACT was also higher in group
      2 (p = 0.01). More patients in group 1 had delayed ambulation (p = 0.04) due to
      abciximab perfusion. In 7 patients in group 1 and 9 in group 2, additional
      manual/mechanical compression was needed for moderate bleeding in the first hours
      (p = NS). One rupture of the femoral artery with need for surgical repair
      (primary failure) and another delayed rupture (48 hours) occurred in group 1
      (both with an associated infection), and 1 pseudoaneurysm in a patient from group
      2, without abciximab but taking warfarin (p = NS). None of the variables analyzed
      determined the occurrence of complications. Only oral anticoagulation determined
      the occurrence of major complications. CONCLUSIONS: User of the Perclose system
      for percutaneous closure of the femoral artery in patients undergoing coronary
      angioplasty with simultaneous use of abciximab was not associated with greater
      morbidity than in patients without glycoprotein IIb/IIIa receptor antagonists.

PMID- 14655310
TI  - Acute coronary syndrome in a diabetic population--risk factors and clinical and
      angiographic characteristics.
AB  - INTRODUCTION: Diabetes is not only a risk factor for coronary artery disease but
      also influences its presentation and evolution. OBJECTIVES: The objective of this
      work is to define the risk factors, clinical and angiographic characteristics,
      and evolution of acute coronary syndrome in a population of diabetic patients.
      METHODOLOGY: We studied 521 patients suffering from acute coronary syndrome,
      consecutively hospitalized in the Cardiology Intensive Care Unit who underwent
      cardiac catheterization during their hospitalization, in terms of risk factors
      for coronary disease, pathology (unstable angina versus acute myocardial
      infarction), coronary morphology, left ventricular function, need for
      intervention during hospitalization, evolution and complications during one-year
      follow-up. The characteristics of the diabetic patients with acute coronary
      syndrome were compared to those of non-diabetic patients. RESULTS: Of the 521
      patients suffering from acute coronary syndrome (391 male), 159 (30.5%) were
      diabetic. The diabetic patients suffering from acute coronary syndrome generally
      presented fewer risk factors for coronary artery disease, with a lower prevalence
      of smoking (p < 0.001), greater prevalence of family history of coronary artery
      disease (p < 0.01), more unstable angina and less acute myocardial infarction
      (both p < 0.001), than the nondiabetic patients. After the acute coronary
      syndrome the diabetic patients more frequently presented disease of the left
      anterior descending artery, left ventricular function was worse and there was a
      greater need for coronary artery bypass graft surgery and less percutaneous
      transluminal coronary angioplasty than in the non-diabetic patients (p < 0.05 for
      all). In terms of evolution, they presented greater complications and more
      mortality over a year (p < 0.05). CONCLUSION: Diabetes constitutes a powerful
      risk factor for coronary artery disease and its complications, and should
      therefore be taken into consideration in clinical approaches to this pathology.

PMID- 14655311
TI  - Non invasive hemodynamic monitorization for AV interval optimization in patients
      with ventricular resynchronization therapy.
AB  - INTRODUCTION AND OBJECTIVE: In patients (pts) with dilated cardiomyopathy and
      intraventricular conduction disturbances, resynchronization therapy improves
      cardiac function and functional capacity. Determination of the optimal AV
      interval is essential to optimize the therapy results and various methods have
      been used in daily practice to obtain such an interval. The aim of this work is
      to assess optimal AV determined by impedance cardiography and compare it to the
      interval previously obtained by transmitral flow Doppler echocardiography.
      PATIENTS: Seven pts were evaluated, five men, mean age of 61 +/- 10 years, with
      dilated cardiomyopathy, intra-ventricular conduction disturbances and heart
      failure, New York Heart Association functional class III or IV. Four pts had
      ischemic cardiomyopathy and three idiopathic. All pts had an implanted
      cardioverter-defibrillator with cardiac resynchronization. METHODS: The optimal
      AV delay was estimated by transmitral flow pulsed Doppler using the method
      previously described by Ritter. Subsequently, cardiac output (CO) was determined
      by impedance cardiography. CO was estimated for different AV delays, beginning
      with 80 ms until occurrence of fusion QRS. The optimal AV delay was defined as
      the value corresponding to the highest measured CO. The ideal AV interval was
      compared between the two methods used. RESULTS: The AV delay determined by
      echocardiography varied between 120 and 170 ms (134 +/- 17 ms). The optimum AV
      delay based on CO estimation varied between 110 and 190 ms (137 +/- 26 ms). There
      was a correlation between the delays determined by the two methods (r = 0.844; p
      = 0.017). CONCLUSIONS: In pts undergoing ventricular resynchronization therapy,
      AV delay optimization based on CO determined by impedance cardiography is
      comparable to that measured by transmitral flow pulsed Doppler. However,
      impedance cardiography seems a more objective and simpler technique.

PMID- 14655312
TI  - Percutaneous embolization of a congenital aortocaval fistula--clinical case.
AB  - Congenital aortocaval fistulae are a rare cause of left-to-right shunt. In this
      clinical case, an 8-year-old child was referred by the family doctor for
      pediatric cardiology consultation after detection of a chest murmur. Cardiac
      auscultation revealed a continuous murmur, best heard on the left sternal edge
      and back. During the study, cardiac angiography showed a large collateral vessel
      in the middle third of the thoracic aorta with a complex and sinuous route that
      ended at the superior vena cava. Percutaneous embolization was performed using a
      coil. Due to the large size of the collateral a total of three coils were
      necessary for complete occlusion. No complications were recorded and six-month
      follow-up confirmed absence of shunt. Compared to the surgical option, this
      procedure is less invasive and apparently with less risk to the patient.

PMID- 14655313
TI  - Quality in interventional cardiology: towards the future.
AB  - Interventional cardiology is an example of a medical field in which rapid
      technological advances have taken place over a short period of time. In the 26
      years since the inception of interventional cardiology, there has been an
      enormous increase in the volume of cases and the number of operators and sites
      performing coronary angioplasty. Coupled with this, in the last decade we have
      witnessed tremendous developments in the techniques, materials and adjunctive
      therapy associated with percutaneous coronary intervention. Health care
      interventions are intended to benefit patients, but they can also cause harm. The
      complex combination of processes, technologies and human interaction that
      constitutes the modern health care delivery system can bring significant
      benefits. However, it also involves an inevitable risk of adverse events that
      can, and too often do, happen. The Joint Commission on Accreditation of
      Healthcare Organizations has defined quality in health care as "the degree to
      which patient care services increase the probability of desired patient outcomes
      and reduce the possibility of undesired outcomes, given the current state of
      knowledge." The establishment of quality standards based on patient outcomes data
      is a rational means of differentiating the quality of health care in the
      marketplace. Institutional variation in patients' baseline clinical risks
      precludes the direct comparison of outcomes across institutions. The application
      of risk adjustment methodology to account for patient differences in these
      treatment outcomes is imperative for legitimate comparison of institutional
      results in the modern era of cardiovascular intervention. The aim of this paper
      is promote reflection on the importance of quality in interventional cardiology
      and, simultaneously, to emphasize the role of health professionals in this
      regard, in daily practice and through their investigations. Another aim is
      encourage the inclusion of risk adjustment methodology to account for patient
      differences, and consequently, to make an accurate assessment of the results
      obtained by different operators and institutions.

PMID- 14655314
TI  - Equivalence trials: methodologic analysis.
AB  - Therapeutic clinical research is based on randomized controlled trials (RCTs)
      that compare a new drug with a placebo or--less frequently--with an active
      substance (a drug with proven efficacy for that disease), trying to determine
      whether one is better than the other, or both are the same. These trials are
      called "superiority trials", because the aim is to prove that the new drug is
      more efficacious than the classic one (or the placebo). Besides superiority
      trials between two drugs, or a drug and a placebo, there are trials called
      "equivalence trials", in which two drugs (or the same drug with two galenic
      formulations) are compared in order to prove their pharmacologic and clinical
      equivalence. Because it is impossible to prove that two (or more) interventions
      are exactly equivalent, these trials have to be designed in such a way as to show
      that the two treatments do not differ by more than a certain pre-defined
      "equivalence margin". This type of trial is especially useful when the classic
      treatment has proven efficacy, but the new one is safer, easier to use or
      cheaper, for example. In this article we present the guidelines which all
      equivalence trials should follow to be considered valid. These methodological
      rules certify as to the equivalence between drugs, eliminating errors and biases
      that are commonly found in the literature.

PMID- 14655315
TI  - Public information about clinical trials and research.
AB  - Be it to restore the confused image of clinical research in relation to the lay
      public, or to develop new ways of accruing healthy volunteers or patients for
      clinical trials, there is a need to draft some guidance on how best to provide
      information on research. Although the French legal and regulatory armamentarium
      in this area is essentially liberal, there is currently little-justified
      reluctance among study sponsors to advertise publicly. A group of academic and
      pharmaceutical industry researchers, assembled for a workshop, together with
      regulators, journalists, representatives from ethics committees, social security,
      patient and health consumer groups and other French institutional bodies, has
      suggested the following series of recommendations: there is no need for
      additional legal or regulatory constraints; sponsors should be aware of and make
      use of direct public information on trials; a 'good practice charter' on public
      communication about clinical trials should be developed; all professionals should
      be involved in this communication platform; communication in the patient's
      immediate vicinity should be preferred (primary-care physician, local press);
      clinical databases and websites accessible to professionals, but also to patients
      and non-professionals, should be developed; genuine instruction on clinical
      trials for physicians and health professionals unfamiliar with such trials should
      be developed and disseminated; media groups should receive at least some training
      in the fundamentals of clinical research.

PMID- 14655316
TI  - Postmarketing evaluation of drugs. Actual efficacy, population exposed and impact
      on public health.
AB  - Round table no. 2 was devoted to the postmarketing evaluation of drugs. The
      debates involved both the questions posed by postmarketing evaluation and the
      methods for responding to them. The major categories of questions likely to be
      posed are as follows: efficacy in actual situations; safety in actual situations;
      prognostic factors and patients responding; place in the therapeutic strategy;
      impact on the healthcare care system; the 'joined' population (those who actually
      obtain benefit); and drug utilisation review. In addition, the methodological
      approaches have been divided into three categories: the experimental approach,
      the observational approach and the modelling approach. Each of these
      methodological approaches has been qualified with respect to each of the
      questions. The objective was neither to establish a classification of the methods
      according to the level of proof, nor to propose methodological formulae. Instead,
      the participants applied themselves to describe the strengths and the limits of
      the different methods for each of the questions in turn. The debates then focused
      on the process of identification of pertinent questions and appropriate methods.
      In this context, the round-table participants applied an analysis of the current
      system of postmarketing study projects and formulated some propositions for their
      improvement. Finally, the place of existing databases in the postmarketing
      evaluation was discussed and the participants emphasised the importance of
      initiating a very detailed assessment of the information that could be provided
      by such databases before instituting ad hoc studies.

PMID- 14655317
TI  - Prevention of drug-induced risks.
AB  - Effective prevention of drug-induced risks depends on an accurate understanding
      of their triggering or predisposing factors, and the quality of information on
      these available to prescribing practitioners and users. All preclinical and
      clinical data available on the proprietary medicinal product concerned should
      facilitate identification of a risk, and these data should be compared with
      existing data on drugs sharing the same mode of action or therapeutic strategy.
      This information should be based on a communication plan adapted to the context
      of the disease under treatment, the therapeutic alternatives available and the
      benefits expected.

PMID- 14655318
TI  - Clinical trials in paediatric oncology. Recommendations for the development of
      new anticancer agents.
AB  - Childhood and adolescent cancers are rare diseases. Despite the progress in
      treatment (more than two-thirds of all cases are cured), cancer remains the
      leading cause of death by disease in children older than 1 year. Access to new
      drugs that are more efficacious or better tolerated is therefore an important
      public health priority. The objective of our round table was thus to take
      inventory of the situation and to propose recommendations aimed at facilitating
      coordinated, rational and more rapid access to new treatments. The active
      participation of paediatric oncologists, parents, pharmaceutical companies and
      regulatory authorities proved not only necessary but very constructive.
      Pharmaceutical companies have developed very few new anticancer agents for
      children during the past 10 years. The round table identified current trends that
      appear propitious: the mobilisation of parents and patients' associations;
      European initiatives to encourage companies to assess drugs in children;
      regulatory initiatives to guide drug development; and the existence of structured
      clinical research networks in paediatric oncology, including for the development
      of early treatment. The round table recommends the following measures to improve
      access to new treatments for children and adolescents with cancer: 1. Conduct
      preclinical paediatric evaluation of all anticancer agents that begin the
      development process for adults (research and validation of treatment targets;
      pharmacological evaluation in relevant experimental models) to help choose the
      agents to study in children. 2. Initiate paediatric clinical development before
      the first application for authorization for adults is filed, when sufficient
      safety and tolerability data are available, that is, after the phase I trials in
      adults and optimally during the phase II trials. 3. Optimise paediatric clinical
      evaluation by defining development plans early and by reducing the duration of
      studies (enlargement of the early treatment research network to ensure adequate
      recruitment; new evaluation methods; better extrapolation of pharmacological data
      from adults to children for dose-finding). 4. Improve information to and
      participation of parents and patients in clinical research for new treatments.
      The prerequisite for the success of this project became rapidly clear to all the
      round-table participants: cooperation and partnership between specialists and
      other scientists from academia, parent associations, pharmaceutical companies and
      regulatory authorities. Only with such cooperation can progress in treatment
      occur and new hopes for recovery be fulfilled.

PMID- 14655319
TI  - Methodology for the evaluation of drugs in pregnant women.
AB  - Although drugs are prescribed during pregnancy with some reluctance, they fulfill
      a real need in some circumstances. Adequate drug evaluation is thus essential,
      either based on efficacy and safety or mainly safety, using available data from
      non-pregnant women. Evaluation methodology is not fundamentally different during
      pregnancy. Recommendations for drug development are formulated on the basis of
      the most common situations as well as specific suggestions, thus raising the
      awareness of the different partners participating in healthcare (institutions,
      the pharmaceutical industry and prescribers). In particular, regulatory and
      economic incentives superimposed upon those recommendations adopted in Europe and
      the US for orphan diseases should be put into place to assist in the evaluation
      of drugs used in obstetrics. Medical needs in obstetrics should be better
      identified, and labelling of drugs for use during pregnancy should be better
      directed towards prescribers; a national registry of pregnancies should be
      established in France.

PMID- 14655320
TI  - Subjective outcome measures of drug efficacy.
AB  - The use of subjective outcome measures for assessing drug efficacy varies
      according to the disease in question. Subjective outcome measures used to
      complement an objective outcome measure can clearly claim the status of a main
      outcome measure. The validation of an instrument follows an appropriate
      methodology that focuses on two points: the methods used for its construction are
      set out and its performance is evaluated in a study. In drug evaluation, the
      importance of the subjective outcome measure should be discussed, depending on
      the aim and the disease. The methodology of the study obeys the same rules as
      when an objective outcome measure is used. The issue of the clinical significance
      of the results should be broached and discussed. Subjective outcome measures
      deserve to be considered in the evaluation of the drug because they provide a
      different and complementary perspective on the disease and the patient, both at
      the time of obtaining the marketing authorization or when reassessing a drug.

PMID- 14655321
TI  - Pharmacogenetic and pharmacogenomic studies. Impact on drug discovery and drug
      development.
AB  - The topics discussed in this article are concerned with studying genomic
      polymorphism and identifying new therapeutic targets, the role of genetics in
      preclinical and clinical drug development, and cultural, regulatory and
      logistical aspects of the development of pharmacogenetics in France. The
      conclusions are that from a physiological, biochemical or genomic point of view,
      the study of human genetic polymorphism has obvious potential value for drug
      development, because it can help to identify new therapeutic targets, and to
      predict drug efficacy and tolerability more effectively. There are already
      several examples of the latter approach, which relies on studying the genetic
      variability of enzymes involved in drug metabolism, and that of the effector
      molecules of the pharmacological activity. Pharmacogenetics could eventually make
      it possible to personalize drug treatments, as methods for analysing genes are
      simplified and their cost reduced. To help attain this still far-off goal,
      certain recommendations have been proposed.

PMID- 14655322
TI  - [Attractiveness of France for clinical trials: evaluation of laboratories and
      promoters].
AB  - Questions have been raised regarding the attractiveness of France versus other
      countries for performing clinical trials. A questionnaire was sent to
      pharmaceutical companies with offices in France to assess their level of activity
      and to get information on the pros and cons of performing phase I-IV
      international clinical trials in France. Eleven companies, of large to medium
      size and representing 44% of the shared market returned answers. In 2001, they
      spent 131 million euros on clinical trials--53% for phase I-III, with a staff of
      1469 (not including Contact Research Organisations)--and involved 21,000
      investigators recruiting 98,000 patients on local budgets, and 2257 investigators
      recruiting 10,270 patients on international budgets. France ranked well as
      regards size of market or resource availability, with an intermediate rank as
      regards costs, access to patients and disease prevalence, and was weak with
      regard to speed of recruitment and quality of investigators. Ways of improving
      France's attractiveness will be discussed.

PMID- 14655323
TI  - A critical analysis of the broker and strengths models of case management:
      identifying a potential framework for community case managers.
AB  - In Canada, case management has been applied to a variety of health care settings
      including the community care system, where case managers have become an integral
      component in the delivery of government-funded, in-home services. Specifically in
      Ontario, home care is accessed through 43 Community Care Access Centres (CCACs),
      and the model currently driving case management practices most closely resembles
      the Broker model. Not only does this create moral distress among the case
      managers, but it also hinders their ability to meet the health care needs of the
      community as current cost containment strategies can lead to suffering and
      emotional distress for a significant portion of the people who are cut from care.
      This article will identify a potential framework for case managers in CCACs. The
      Strengths model offers a framework that is consistent with the goals of Ontario
      case managers and is committed to client autonomy, empowerment, and client-driven
      care. Given the multitude of health care challenges facing CCAC case managers
      today, the Strengths model of practice has the potential to contain and maintain
      costs without compromising the psychological wellbeing and health care needs of
      the community.

PMID- 14655324
TI  - Care management in long-term care insurance: meeting the needs of policyholders?
AB  - Despite the increase in long-term care insurance (LTCI) sales, little attention
      has been given to the quality of services provided to policyholders receiving
      benefits. This article describes a qualitative analysis of care management (CM)
      services within LTCI. Key components of analysis included the assessment and care
      planning process, service coordination, monitoring of policyholder needs,
      discharge planning, and consumer knowledge and satisfaction. Extensive case
      record reviews, including longitudinal in-person and telephone interviews with
      policyholders, caregivers, and other stakeholders, were performed to gain insight
      into the CM process as experienced by LTCI policyholders under the California
      Partnership for Long-Term Care. Results suggest that CM may be somewhat
      restricted under LTCI. While the basic CM services available to policyholders may
      be appropriate for addressing the simple needs, individuals with chronic and
      unstable disabling conditions may require a more comprehensive form of CM.

PMID- 14655325
TI  - The effect of case management in substance abuse on health services use.
AB  - This study evaluated the effect of case management, as a supplement to
      traditional substance abuse treatment, on health services utilization. Data for
      the study were taken from the Iowa Case Management Project (ICMP). The ICMP
      evaluated case management using a randomized research design. Residential clients
      who agreed to participate were randomly assigned to one of four case management
      conditions. The first three conditions were variations of the Iowa Case
      Management (ICM) model: (a) Inside Case Management, (b) Outside Case Management,
      and (c) Telecommunications. Case management clients in these three conditions
      were eligible for 12 months of case management. The fourth condition, the control
      condition, received no additional case management through ICMP. The study results
      show that the use of case management decreased the use of mental health services
      while increasing clients' use of inpatient care, access to physician, and the
      emergency room. It was expected that case management would increase, in the short
      run, the substance abuser's use of health services due to staying longer in
      treatment and seeking medical care that would be otherwise neglected. However, in
      the long run such early use of necessary health services might reduce the
      clients' use of avoidable, more costly care. Case management should be looked at
      as an investment with long-term payoffs.

PMID- 14655326
TI  - Eliminating health disparities associated with long-term care to promote graceful
      aging in place.
AB  - The aging of the population in the United States along with the high prevalence
      of chronic diseases among them requires that a system of care be developed that
      will permit seniors to age gracefully in place even when in ill health. Such a
      system will encourage healthy lifestyles, provide expert coordination of care,
      involve friends and family, and make seniors informed and active participants in
      decisions about their health care. Overcoming the barriers to the establishment
      of such a system is a challenge for the 21st century.

PMID- 14655327
TI  - Long-term care preferences and attitudes among Great Lakes American Indian
      families: cultural context matters.
AB  - This research examines the role of family and culture in planning for future long
      term care needs and preferences among 252 elders age 55 and older and 74 middle
      generation children of Great Lakes American Indians living in three residential
      areas: urban, reservation, and off-reservation rural. Findings show that both
      generations prefer a non-institutional home-based choice for care if needed, and
      that acculturation levels influence those choices. Level of acculturation
      differed by area of residence.

PMID- 14655328
TI  - [Health is more than just health care. Working in poor countries gives new
      perspectives on the whole spectrum of the medical profession].

PMID- 14655329
TI  - [Pain more painful in women. Gender perspective neglected in research on the
      biological mechanisms of pain].
AB  - There are some sex differences in the perception of defined noxious stimuli, with
      females being more sensitive than males in both rodents and humans. Using imaging
      techniques gender differences of the brain were recently demonstrated in
      neurophysiological response and pain perception to heating of the skin. Many
      chronic pain states are more common and/or aggressive in women than in men, i.e.
      migraine, pain in rheumatic disease and some cardiac pains. There are also sex
      differences in the pain relieving effects of certain drugs, i.e. opioids and
      NSAID:s. Since the details of the mechanisms which govern the biological
      differences between the sexes in health and disease are largely unknown there is
      scope for additional studies. It is anticipated that such research will reveal
      new important gender related data which will elucidate the background to a number
      of ailments and contribute to the development of better and/or quite new
      treatments of different patients, e.g. patients with chronic pain syndromes.

PMID- 14655330
TI  - [Tinnitus treatment is guided by etiology. Noise, stress or anxiety/depression
      plausible causes].
AB  - Tinnitus may be a clinical symptom of disturbances in the auditory system but
      also of stress. Noise exposure may be a trigger. Severe tinnitus may have an
      impact on the working capacity, and in the management of tinnitus. It is
      essential to differ between the etiologies to the emergence of tinnitus and to
      the suffering of it. The majority of the adults, and a third of the children
      seeking help for tinnitus have anxiety and/or depressive disorders. Consequently,
      it is of great importance to early identify and treat these conditions.

PMID- 14655331
TI  - [Radiologic diagnosis of liver diseases--method development taking place on a
      wide front].
AB  - Radiological techniques, ultrasonography (US), computed tomography (CT) and
      magnetic resonance imaging (MRI) are increasingly being used to detect and
      characterise liver diseases. US-guided percutaneous approaches are performed to
      obtain tissue specimen from the liver and for local treatment of liver tumours.
      Technical developments of all different modalities, new contrast agents for US
      and MRI, improvements in liver resection techniques as well as several ways to
      locally treat liver tumours have emerged during the past few years. In this
      overview we summarise the present status of different imaging modalities in the
      diagnosis of liver disease.

PMID- 14655332
TI  - [Important to reduce the risk of infections in residential facilities].
AB  - In view of the fact that Swedish nursing home care represents an integrated form
      of residential housing and health care and it is not possible to classify
      infections as either "health-care-associated" or "community-acquired". Thus it is
      not appropriate to use the same surveillance systems as those used in hospitals.
      The presence of known risk factors for infection--either related to medical
      devices or due to underlying illness--could however be monitored. Antibiotic
      treatment favours selection of resistant bacterial strains and should thus be
      used with prudence. At December 8th, 2000, we investigated the presence of 20
      risk factors and antibiotic treatment among 2,817 residents in nursing homes in
      Uppsala county. Seventeen out of 20 risk factors were all present in less than 1
      per cent of the residents. Pressure ulcers or leg/foot-ulcers occurred among 3.2%
      each, and 7.6 per cent of the residents had an indwelling urinary catheter. About
      6% of the residents were treated with at least one antibiotic. Urinary tract
      infection was the main reason for treatment. The investigation shows that
      training of nursing home staff by the infection control team should focus on hand
      hygiene and routines for wound care and urinary catheter care in order to
      minimize the risk for infections among residents.

PMID- 14655333
TI  - [Improvements of standards in clinical diagnosis of stroke are needed].
AB  - A detailed history, neurological examination, and assessment of function are
      essential procedures in all patients with stroke. Findings need to be adequately
      documented in the medical records. In a recent study, the documentation of 106
      core items in stroke management, as specified in the Swedish National Guidelines
      for Stroke Management, was evaluated in the records of 70 randomly selected
      stroke patients treated at 17 hospitals in two county councils between March and
      May of 2001. The initial screening process and neurological examination were
      adequately documented in fewer than 50% of the patients. Clinical workup of
      stroke in routine practice needs to be improved. It is proposed that the
      documentation of core items be standardized, and that a well validated stroke
      scale (NIH Stroke Scale), at present mainly used in conjunction with acute
      thrombolytic therapy, be generally applied to all patients with stroke.

PMID- 14655334
TI  - [Goodbye hunger! An agriculture-health care project reduced dramatically
      undernutrition in a poor village in Kenya].

PMID- 14655335
TI  - [A powerful leader in changing times. Lessons learnt from a symposium dedicated
      to Borje Uvnas, professor of pharmacology].

PMID- 14655336
TI  - [Suffix-historical contribution about -itis. The meaning of the concept of
      "inflammation" is a new invention].

PMID- 14655337
TI  - [Out-of-date theories and governmental directives obstruct efficient
      rehabilitation].

PMID- 14655338
TI  - [The sick leave explosion is a problem full of nuances].

PMID- 14655339
TI  - ["Patients' demand is wrongly interpreted!. Patients with "care allowance" will
      become powerful actors on the health care market].

PMID- 14655340
TI  - [A reply on Region Skane: necessary structural changes will not benefit by victim
      mentality at small hospitals].

PMID- 14655341
TI  - [Possible to take medical responsibility for obstetric activities at the Kiruna
      BB].

PMID- 14655342
TI  - [Easier to be correct with the new sickness certificates].

PMID- 14655343
TI  - [For and against potassium cyanide in "Doctor Glas"].

PMID- 14655344
TI  - [Optimization of spatial arrangements and patterns for shelterbelts or
      windbreaks].
AB  - Spatial arrangements and patterns of shelterbelts or windbreaks are the key
      factors influencing the shelterbelt structures, shelter benefits, and shelterbelt
      sustainability. In order to keep the shelter benefits and achieve the
      sustainability of shelterbelts, it is necessary to keep the reasonable
      arrangements and patterns in spatiality and the continuation in time. Based on
      the investigations on the shelterbelts, which were established in 1992 as the
      models in Shuangjingzi Township, Changtu County, Liaoning Province, and combined
      with the experiences and practices of shelterbelt management, the authors studied
      and summarized the arrangements and patterns of shelterbelts, which included the
      direction of a single shelterbelt and shelterbelt-networks, the arrangement of
      tree composition in a shelterbelt, and the mixture of tree species for
      shelterbelts. Additionally, the spacing intervals between shelterbelt and the
      spatial patterns for regional shelterbelts were also discussed. The results
      indicated that the direction of both single shelterbelt and shelterbelt-networks
      should be perpendicular to the disaster winds. It is better for the structure of
      a shelterbelt to arrange the trees in triangle form in a shelterbelt. According
      to the edge effect, the tree species which grow slowly should be arranged in the
      edge lines, but the tree species which grow fast should be arranged in the inner
      lines of the mixed shelterbelts. Optimal spacing intervals between windbreaks
      could be predicted from the indices of a given windbreak structure (porosity),
      percentage of desired wind speed reduction, and tree growth model (model for
      determining initial protective maturity age). The patterns of shelterbelts in
      large scale should be evaluated and arranged according to the principles of
      landscape ecology. The results mentioned above would provide the evidences for
      shelterbelt sustainable management.

PMID- 14655345
TI  - [Relationship between photo-inhibition of photosynthesis and reactive oxygen
      species in leaves of poplars suffering root osmotic stress].
AB  - To know more about the photo-inhibition of photosynthesis under field conditions,
      its relationship with reactive oxygen species (ROS) in leaves of poplar clone
      seedlings was studied under osmotic stress conditions. With the increasing
      duration of osmotic stress and the enhancement of stress intensity, the ROS
      level, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity
      increased, while the activities of catalase (CAT) and ascorbate peroxidase (APX)
      decreased, resulted in the unbalanced ROS metabolism and intensified photo
      inhibition. The inhibition of SOD activity by copper diethyldithiocarbamate or
      the accelerated generation of O2-. with methyl viologen (MV) could also induce
      the photo-inhibition. The decrease of the ability of poplar clone seedlings in
      scavenging H2O2 under osmotic conditions limited the dissipation of excess light
      energy and the role of photosynthetic apparatus in protecting against photo
      inhibition through Mehler reaction. Photo-inhibition might be related to the
      accumulation of ROS.

PMID- 14655346
TI  - [Effects of ultraviolet-C irradiation on membrane lipid peroxidation and activity
      of PS II electron transport in chloroplasts of Taxus cuspidata needles].
AB  - The isolated chloroplasts of Taxus cuspidata needles treated with 12 W.m-2 of
      ultraviolet-C (UV-C, 254 nm) irradiation were studied under laboratory
      conditions. The results showed that with the increase of UV-C irradiation, the
      carotenoids (Car) and glutathione (GSH) contents and superoxide dismutase (SOD)
      activity were decreased, while the malondialdehyde content (MDA) and the relative
      permeability of chloroplasts membrane were increased to various extents. The PS
      II electron transport activity was conspicuous decreased, which had a significant
      inverse ratio with photosynthetically active radiation (PAR). UV-C irradiation
      was insensitive on chlorophyll. The results indicated that membrane lipid
      peroxidation of chloroplasts caused by UV-C radiation was the reason of the
      decrease of PS II electron transport activity.

PMID- 14655347
TI  - [A preliminary study on the chemical properties of precipitation, throughfall,
      stemflow and surface run-off in major forest types at Dinghushan under acid
      deposition].
AB  - Studies on the chemical properties of precipitation, throughfall, stemflow and
      surface run-off in major forest types at Dinghushan under acid deposition showed
      that the pH value of precipitation was about 4.90, and the frequency of acid rain
      was over 62%. In broad-leaved forest, the pH value of precipitation was lower
      than that of throughfall, but higher than that of stemflow and especially the
      surface run-off, indicating that the soil was naturally acidified. In mixed
      forest, both throughfall and surface run-off had a higher pH value, but stemflow
      had a lower pH value than precipitation. The throughfall and stemflow were more
      acidified than precipitation in coniferous pine forest, but the surface run-off
      had a higher pH value than precipitation. These results suggested that among the
      three major forest types at Dinghushan, the canopy of broad-leaved forest had the
      highest buffering ability, whereas for the soil, the coniferous forest had the
      highest soil buffering capacity. The concentrations of nutrient elements, such as
      P, K, Ca, Na and Mg in the throughfall, stemflow and surface run-off were higher
      than those in bulk precipitation in all forests at Dinghushan, some even 10 times
      higher, indicating that a large amount of nutrients were leached from the canopy.
      The concentrations of nutrient elements in stemflow were higher than those in
      throughfall in all forests, and the concentration of nutrient elements in surface
      water was higher than those in atmospheric rainfall. Coniferous forest had a
      higher concentration of nutrients in the throughfall and stemflow and a lower
      nutrient concentration in the surface run-off than other forest types, which
      implied that nutrient loss was more serious in broad-leaved and mixed forests
      than in coniferous forests.

PMID- 14655348
TI  - [Method for measurement of optical stratification porosity (OSP) and its
      application in studies of management for secondary forests].
AB  - Secondary forest is the main body of forests in China, and hence, its management
      plays a very important role in the projects of natural forest conservation and
      ecological environment construction in this country. The structure, especially
      the vertical stratification structure of secondary forest is one of the key
      factors in the management of secondary forest, and can be considered as the base
      of its management. Based on previous studies, the concept of stratification
      porosity was introduced, and the optical stratification porosity (OSP), which is
      the two dimensional alternative measurement of stratification porosity, could be
      used to represent the vertical stratification structure of secondary forest. The
      method using hemispherical photographic silhouette (photographic silhouette taken
      with fisheye lens) to estimate the OSP of a forest stand was also introduced. In
      addition, the possible applications of OSP in studies on the structure and
      restoration ecology of secondary forest, and the theory and techniques for the
      management of secondary forest were also given in this paper.

PMID- 14655349
TI  - [Effects of soil temperature and moisture on soil respiration in different forest
      types in Changbai Mountain].
AB  - The effects of soil temperature (0, 5, 15, 25, 35 degrees C) and water content on
      soil respiration in three forest types in Changbai Mountain were evaluated in
      laboratory condition. The results indicated that the soil respiration rate was
      positively correlated to soil temperature from 0 to 35 degrees C and it increased
      with soil water content from 0.21 to 0.37 kg.kg-1. The soil respiration rate
      decreased with soil water content when water content was over the range. The
      result suggested the interactive effects of temperature and water content on soil
      respiration. There were significant differences in soil respiration among the
      various forest types and the highest was in broad leaf Korean pine forest, then
      in erman's birch forest, and it was the lowest in dark coniferous forest. The
      optimal condition for soil respiration in broad-leaved Korean pine forest was at
      35 degrees C under 0.37 kg.kg-1 water content, and it was at 25 degrees C under
      0.21 kg.kg-1 in dark coniferous forest and at 35 degrees C under 0.37 kg.kg-1
      water content in erman's birch forest. Because the forests of broad leaf Korean
      pine, dark coniferous and erman's birch are located at various altitudes, the
      soil temperatures had 4-5 degrees C variation in different forest types during
      the same period. The soil respiration rates measured in brown pine mountain soil
      were lower than those in dark brown forest and they were higher in mountain grass
      forest soil than those in brown pine mountain soil.

PMID- 14655350
TI  - [Quantitative simulation on the vertical distribution of soil organic matters in
      mountainous soil profiles in the subtropical area, south China].
AB  - Quantitative descriptions of soil organic matter (SOM) dynamics, i.e., their
      distribution, turnover and movement, are essential for the running of the
      simulation of terrestrial ecosystem organic matter models. In this study, based
      on utilizing SOM diffusion-translation-decomposition model, two soil profiles
      were selected in different vegetation zones at Dinghushan Mountain for
      quantitative studies on SOM dynamics and their controlling factors. SOM were
      divided into three kinds of compartments: rapid compartment with turnover rate of
      0.1-1.yr-1, slow compartment with turnover rate of 0.002-0.02.yr-1, and stable
      compartment with turnover rate of 0.0001-0.001.yr-1. The numerical results
      suggested that SOM distribution in soil profile in subtropical mountainous areas
      of south China obeyed the law of diffusion motion, translation motion and
      decomposition. The turnover rate of SOM rapid compartment was 0.483.yr-1 in the
      forest vegetation zone, and was 0.694.yr-1 in the shrub vegetation zone. The
      turnover rates of SOM slow compartment in the two kinds of vegetation zones were
      both 0.02.yr-1, and the turnover rates of SOM stable compartment in the two kinds
      of vegetation zones were both 0.001.yr-1. SOM diffusion rate and translation rate
      for the forest vegetation zone was 4 cm2.yr-1 and 0.2 mm.yr-1, respectively, and
      the two rates of the shrub vegetation zone were 1 cm2.yr-1 and 0.5 mm.yr-1,
      respectively. The obvious discrepancy between numerical values and measuring
      values for SOM content occurred in the 0-10 cm sections of the profiles, which
      might be due to the fact that the upper sections were at the interface between
      lithosphere and atmosphere, and were influenced directly by changes of climatic
      and environmental factors. The two kinds of values for SOM content were identical
      below the upper section of the profiles, and it indicated stable pedogenesis
      environments. Diffusion motion had obvious influences on SOM vertical
      distribution, and translation motion had clear impacts on SOM distribution only
      in the upper 0-10 cm section. Comparison analysis suggested that SOM dynamics
      were controlled mainly by soil profile qualities such as SOM content, clay
      content, soil fabric, void types and their developments, soil fauna and
      microorganism activities, etc. With the increasing of primary production of
      aboveground vegetation, the turnover rate of SOM rapid compartment decreased and
      SOM content increased, which provided scientific basis for increasing soil carbon
      sink through anthropogenic effects.

PMID- 14655351
TI  - [Ecological distribution of soil microorganism in artificial greenbelt in
      hinterland of Takilimakan Desert and their relations with soil factors].
AB  - Studies on the distribution of soil microorganisms in the artificial greenbelt in
      hinterland of Takilimakan Desert and the effects of soil features on the
      distribution showed that under saline water irrigation, the activities of soil
      microorganisms increased sharply, and the soil structure and nutrient status were
      improved. Among soil microorganisms, bacteria were predominant, actinomyces were
      the next, and fungi were the least. There were more microorganisms in upper than
      in deeper soil layers. Soil microorganisms near shelter-forest had a higher
      activity, and their quantities over 3 m from shelter-forest were almost equal to
      those in shifting sand. The quantities of soil microorganisms varied with
      seasons, and there were distinct differences among different sites of forests.
      Among the measured 11 soil factors, the interactions between pairs of soil
      available phosphorus-available potassium, organic matter-available potassium,
      available nitrogen-available potassium, available nitrogen-available phosphorus,
      organic matter-available phosphorus, available phosphorus-available nitrogen,
      total nitrogen-available potassium, available potassium-available phosphorus,
      total nitrogen-available phosphorus, and water contents-available nitrogen were
      significant, with the correlation coefficients of 1.37-2.58. The direct effects
      of available phosphorus, available nitrogen, and total nitrogen on the microbial
      quantity were significant, with the coefficient of 1.01-2.58.

PMID- 14655352
TI  - [Dynamics of soil inorganic nitrogen in middle mountain moist evergreen broadleaf
      forest under different disturbance intensities in Ailao Mountain].
AB  - The effects of three different intensities of disturbance on soil NH4(+)-N and
      NO3(-).N contents were studied in three community types (primary Lithocarpus
      xylocarpus forest, secondary oak forest, and tea plantation, which represent
      three different intensities of disturbance). The results showed that the contents
      of inorganic nitrogen in soil (0-15 cm) of three community types had marked
      differences. Soil organic matter and total nitrogen decreased, while C/N ratio
      increased, with the increasing intensity of the disturbance. Simultaneously, the
      potential lose of NO3(-)-N increased. It suggested that the disturbance was not
      in favor of the retainment of soil fertility and the positive development of
      community succession. The soil organic matter, total nitrogen and C/N ratio were
      basically same at different spatial sites in same community, while the NO3(-)-N
      contents were obvious difference. This implied that soil NO3(-)-N content was
      less stable than NH4(+)-N. In addition, NH4(+)-N was the major component of the
      soil inorganic nitrogen, accounted for 95.5%-99.3% of the total content of soil
      inorganic nitrogen.

PMID- 14655353
TI  - [Properties of potassium loss from red soil slope land in different farming
      systems].
AB  - The properties of potassium loss in red soil slope field under six cultivations
      were studied. The results showed that potassium lost mainly with bed load and
      runoff on surface of soil. The potassium lost mostly with runoff in slope field
      under contour, contour dam cultivated ways with less sediment except the fallow,
      under which the loss of potassium with bed load equaled to the loss of potassium
      with runoff. The potassium lost mostly with bed load in slope field under
      straight, grass strip and contour ditch cultivated ways with more sediment, and
      particulate potassium was the main form of potassium lost in runoff. Compared
      with straight cultivated way, other cultivated ways reduced soil potassium loss
      significantly. Contour, fallow, and contour dam cultivated ways were better than
      straight and grass stripe cultivated ways on controlling potassium loss. In the
      year of 2000, the potassium loss was mainly occurred during May to August
      accounting for 87.24-100% of total annual lost.

PMID- 14655354
TI  - [Effect of sulfur fertilization on yield production and sulfur content of crops
      and pasture in north China].
AB  - Pot experiment on 3 crops (wheat, corn, oilseed rape) and a pasture (clover)
      under 5 levels (0, 5, 10, 20, 40 mg.kg-1) of sulfur (S) was carried out to study
      S application on yield production, S contents and their relationship of these
      crops. The results showed that under S application, the biomass of four plants
      increased by 5-32%, and the grain yield increased by 3-20%. The contents of S
      varied with different corps, for example, the content of S in the oilseed rape
      was the highest (0.479-1.228%), and that in corn was the lowest (only 0.043
      0.091%). The contents of S in different plant parts of the same crop had a
      positive correlation with content of S application. Both the biomass and grain
      yield for all the crops except the clover had a close correlation with the
      content of S application. With available S in the soils increased, the amount of
      S absorbed by crops was increased at the beginning, and then decreased after
      reached the peak.

PMID- 14655355
TI  - [NO3(-)-N leaching and distribution in soil profile in dry highland of Loess
      Plateau under long-term fertilization].
AB  - The NO3(-)-N accumulation and distribution in soil profile of Loess Plateau dry
      highland were studied by long-term field trials. The results showed that NO3(-)-N
      was accumulated in the soil profile under N-fertilization. Application of P
      fertilizer or organic manure reduced the NO3(-)-N content and its leaching depth
      in the soil profile. The deepest depth of NO3(-)-N accumulation was 120-200 cm
      under N treatment, and the peak of the accumulation was the highest in NPM
      treatment, with the depth of 60-120 cm. The NO3(-)-N accumulation depth was 80
      140 cm for NP. Without nitrogen application, there was no evident accumulation of
      NO3(-)-N in soil profile. The more nitrogen used, the more NO3(-)-N accumulated
      in soil profile. Under the same nitrogen application rate, NO3(-)-N accumulation
      might decrease with increasing P application.

PMID- 14655356
TI  - [Decomposing effect of chemical-biological decomposing combined technique on rice
      straw and its fourier transform infrared spectroscopy].
AB  - The effects of several chemical-biological combined decomposing techniques
      (CBCDT) on the decomposition of rice straw were studied by fourier transform
      infrared spectroscopy (FTIR). The results showed that under CBCDT treatments,
      rice straw could be better decomposed than in control. After seven days under
      CBCDT treatments, the straw turned into brown, and was easy to be broken down and
      obviously decomposed. FTIR spectra indicated that under chemical agent A
      biological agent A combined treatment, hydroxyl, ketonic carbonyl, methyl,
      methylene, methane and aliphatic compounds decreased, proteins and amino acids
      completely decomposed, but aromatic compounds (specially substituted group)
      increased, and hence, the humification of straw was accelerated. The effects of
      different decomposing agents on straw were decreased in the order of chemical
      degrade agent A > chemical degrade agent B, biological degrade agent A >
      biological degrade agent B > biological degrade agent C. The chemical agent A
      biological agent A combined treatment was the most effective among several
      treatments.

PMID- 14655357
TI  - [Effect of different cultivation practices on Fe and Cd content in iron plaque
      outside rice root and Cd content in rice root].
AB  - The effects of different cultivation practices-traditional flooding (TF), film
      mulching (FM), straw mulching (SM), and wetting cultivation (WC)-on Cd
      concentrations in Indica and Japonica roots and on Cd and Fe concentrations in
      iron plaque outside the roots were studied at different growth stages (tillering,
      booting, filling and harvest) with a Cd-polluted soil. The results showed that in
      all practices, the mean Fe concentration in iron plaque and the mean Cd
      concentration in roots of Japonica at tillering stage were 6.37 mg.mg-1 and 25.49
      mg.kg-1, and greater than those of Indica, which were 4.52 mg.mg-1 and 16.37
      mg.kg-1 respectively; at booting stage, the mean Fe and Cd concentrations in iron
      plaque and the mean Cd concentrations of Japonica were 1.60, 16.35 and 54.68
      mg.kg-1, and greater than those of Indica, which were 1.06 mg.mg-1, 9.56 and
      43.31 mg.kg-1, respectively; at filling stage, the Fe concentrations in iron
      plaque of Japonica in SM and WC were 0.89 and 1.00 mg.mg-1, and those of Indica
      were 0.63 and 0.30 mg.mg-1; in all practices, the mean Cd concentrations in iron
      plaque and root of Japonica were 15.23 and 73.68 mg.kg-1, and those of Indica
      were 3.46 and 52.38 mg.kg-1; at harvest stage, the Fe concentration in iron was
      plaque of Indica in TF was 1.21 mg.mg-1 and that of Japonica was 0.65 mg.mg-1,
      but that of Japonica in SM was 0.94 mg.mg-1 and that of Indica in SM was 0.55
      mg.mg-1; the Cd concentration in iron plaque of Japonica in WC was 7.96 mg.kg-1,
      and that of Indica was 5.09 mg.kg-1; the mean Cd concentration in root of
      Japonica was 54.53 mg.kg-1 and that of Indica was 35.91 mg.kg-1 in all practices.

PMID- 14655358
TI  - [Effects of rhizobia on morphological distribution of Cu, Zn and Cd in soil].
AB  - Red soil from Chenzhou of Hunan and brown soil from Gongyi of Henan were
      collected and treated with Cu (NO3)2, Zn(NO3)2 or Cd(NO3)2, respectively for 2
      weeks, and Rhizobium fredii strain HN01 was inoculated. Sequential extraction
      method was employed to investigate the forms of Cu, Zn and Cd in the examined
      soils with the absence and presence of rhizobia. The results showed that after
      inoculation, the total amount of solid-bound Zn decreased 10%, and the amount of
      Zn associated with carbonate, Mn oxides, and organic matter fraction decreased 9
      26%. No significant change was observed for the total amount of Zn combined with
      the solid phase of red soil in the presence of rhizobia. However, the amount of
      specifically adsorbed and Mn oxides bound Zn decreased, while the amount of
      exchangeable Zn increased. Inoculation of rhizobia depressed the release of Cu to
      the soil solution, and increased the total amount of Cu associated with the solid
      phase of brown soil. The increase of the amount of exchangeable Cu and of the Cu
      in fractions of carbonate, Mn oxides and organic matter ranged from 20% to 54%.
      There was no significant change for the level of Cd in the solution in both soils
      after rhizobia inoculation. The amount of exchangeable and organic Cd increased
      22% and 11%, while the specifically adsorbed, and Mn oxides bound Mn decreased
      14% and 29%, respectively. The different influence of rhizobia on the
      morphological distribution of test heavy metals in two soils was mainly ascribed
      to the soil pH changes.

PMID- 14655359
TI  - [Root colonization and nodulation of Sinorhizobium fredii HN01DL in Glycine max
      rhizosphere].
AB  - Rhizobox-soil microcosms studies on the colonization, dispersal and nodulation of
      Sinorhizobium fredii HN01DL marked with luxAB gene in Glycine max rhizosphere
      showed that the colonization dynamics and the density of HN01DL in non-sterilized
      rhizobox-soil microcosms were different from those in sterilized rhizobox-soil
      microcosms. The colonization density of the former reached the maximum (8.65 log
      cfu.g-1 root) 12 days after the coated seeds planted, and that of the latter
      decreased rapidly at the early stage and achieved the maximum (6.88 log cfu.g-1
      root) 15 days afterwards. Furthermore, the colonization density of HN01DL reached
      the maximum (7.05 log cfu.g-1 root) in section A (0-4 cm) of root system 5 days
      after seeds planted, decreased slowly and kept a relative stable level until 19
      days, and began to rise up again 33 days afterwards. The strain could also
      disperse to the place of 16 cm from seed to root tip by 46 days after seed
      planted. HN01DL maintained a constantly higher colonization density level in
      section A of root system, formed the largest number of luminescent nodules (total
      16.3, dominantly located in main root of section A), and had the highest
      luminescent percentage (68.8%). The luminescent nodule percentage decreased
      gradually along section A to E of root system, and no luminescent nodule was
      detected in section E of root system.

PMID- 14655360
TI  - [Effects of sunlight and temperature on ultrastructure and functions of
      chloroplast of cucumber in solar greenhouse].
AB  - Studies on the effects of sunlight and temperature on the ultrastructure and
      functions of leaf chloroplasts of cucumber (Cucumis sativus L.) in solar
      greenhouse showed that the size of cells, chloroplasts, and starch grains and the
      number of chloroplast, grana, grana lamella and grana thickness of leaf
      chloroplast of cucumber increased with lowering leaf position. The microstructure
      of leaves and the ultrastructure of chloroplast of cucumber leaves were different
      because of the difference of temperature and sunlight among different months. In
      January, the light intensity was lower, and the cell size of cucumber leaves was
      larger than that in May, but the number of chloroplasts was less than that in
      May. The relationships between photosynthetic rate (Pn) and ultrastructure of
      chloroplast of cucumber leaves were not direct and very close. The Pn of the
      fourth leaf of cucumber was the highest, that of the first spreading out leaf was
      the second, and the near ground leaves had the lowest Pn. The primary reasons of
      the difference of Pn among different position leaves were that the leaf age and
      accepted light intensity were different. If different position leaves of cucumber
      accepted the same sunlight intensity, the difference of Pn among leaves of
      different positions would be smaller. Less efficient light hours and lower light
      intensity were the main factors influencing cucumber growth and yield in solar
      greenhouse. Comparatively, under sunny circumstance, the restriction of
      temperature on cucumber growth was very small, but in cloudy days, lower
      temperature induced by low light intensity became a key factor that restricted
      cucumber growth.

PMID- 14655361
TI  - [Validation of the ALMANAC model with different spatial scale].
AB  - The ALMANAC model was validated in a drought-stressed year and in a period from
      1989 to 1998 at different sites of Texas to evaluate its ability in simulating
      maize and sorghum yields at different spatial scales and to extend its
      application range. There were 11 sites for maize and 8 sites for sorghum in plot
      size simulations, and 9 counties for maize and sorghum in county level
      simulations. The model showed similar accuracy in simulating both plot-size and
      county level mean grain yields. It could also simulate single-year yields under
      water-limited climatic conditions for several sites and mean county yields of
      maize and sorghum, and had small CV values of mean yields for a long-term
      prediction. The mean error was 8.9% for sorghum and 9.4% for maize in field scale
      simulations, and was only 2.6% for maize and-0.6% for sorghum in county level
      mean yield simulations. Crop models often require extensive input data sets to
      realistically simulate crop growth. The development of such input data sets is
      difficult for some model users. The soil, weather, and crop parameter data sets
      developed in this study could be used as the guidelines for model applications in
      similar climatic regions and on similar soils.

PMID- 14655362
TI  - [Effects of growing process and climatic conditions on grain quality of spring
      sown wheat].
AB  - In the period of 1998-2000, 10 wheat varieties were used to study the effects of
      growth, development process and climatic conditions on the quality of wheat
      grains through spring sowing experiments in Beijing. The results showed that
      there were no significant variations on the quality traits among the varieties
      while there were significant variations among different years. The most
      significant negative correlation had been shown between the days from sowing to
      ripening and hardness of the grains and between the days from heading to ripening
      and the content of wet gluten of the grains. There was a significant negative
      correlation between day-night temperature difference during the period from
      heading to ripening and content of NIR protein. The results also showed that
      there was most significant negative correlation between total radiation, day
      night temperature difference and the content of wet gluten of the grains. There
      was significant positive correlation between total sunlight and the content of
      wet gluten of the grains. The significant negative correlation was present
      between sedimentation value and total radiation, total sunlight, average
      temperature of daytime, day-night temperature difference.

PMID- 14655363
TI  - [Temporal and spatial distribution characteristics of the crop root in
      intercropping system].
AB  - The ecological mechanism of competition and compensation between the crop root
      systems of two different intercropping patterns, wheat-soybean and corn-cabbage,
      was studied by field experiment. The results showed that the annual growth peak
      of wheat-soybean roots in intercropping was interlacing, the growth of root
      weight and length expressed synchronism, and the peak of root weight was appeared
      earlier than that of root length. The vertical distribution of the two crops'
      root system in two intercroppings was reduced gradually along with soil depths,
      which also showed that the multiple growth waves moved progressively. The root
      system distributed horizontally in intercropping system also showed a clearly
      unbalanced distribution. The root system distribution of out-row for corn
      elongated 20.4-40.8 cm to cabbage rows, but that of cabbage elongated only 8.5
      12.6 cm to corn. The cross extent of root systems in corn-cabbage intercropping
      was decreased from 40.2 cm to 20.1 cm by fertilization, and the place of cross
      point for root concentrated region was changed from 20.5 cm to 12.4 cm below soil
      surface by fertilizer supply. The place of cross point for root concentrated
      region was an important index to decide the degrees of competition.

PMID- 14655364
TI  - [Multiplication technique of rice T(P) GMS line with double low critical
      temperature values using cold water irrigation].
AB  - In this paper, cold-water irrigation multiplication technique was used to solve
      the difficulty of multiplying rice TGMS line 96-5-2S(Oryza sative L.) with double
      low critical temperature values under natural air temperature condition. The
      results indicated that irrigating rice TGMS line 96-5-2S with different
      temperature underground cold water from the stage of pistil and stamen primordia
      differentiation to the stage of pollen filling for 15 days, and keeping the water
      depth 18-22 cm, the seed set rate of 96-5-2S decreased with increasing irrigating
      water temperature. When the average temperature of irrigation water was 18.5-19.8
      degrees C, the seed set rate ranged from 40.5% to 57.6%, and the yield ranged
      from 3.30 t.hm-2 to 4.35 t.hm-2. While the temperature was 20.5-21.3 degrees C,
      the seed set rate and yield sharply decreased to 2.5-10.4% and 0.21-0.90 t.hm-2,
      respectively. When the average temperature was 22.3-23.5 degrees C, both the seed
      set rate and yield were zero. Under the same irrigation water temperature
      (average 19.8 degrees C) and the same irrigating period (phase IV to phase VII),
      the seed set rate and yield of 96-5-2S with deep water irrigation (18-22 cm) was
      very significantly higher than those of 96-5-2S with shallow water irrigation (7
      10 cm). Under the conditions of same irrigation water temperature (average 19.8
      degrees C) and same water depth (18-22 cm) but different irrigating periods (15
      days from phase IV to phase VII, 20 days from phase III to phase VII, and 25 days
      from phase II to phase VII), the difference of seed set rate and yield of 96-5-2S
      between 15-day treatment and 20-25-day treatment was not significantly different.
      It is confident that 96-5-2S could multiply with underground cold water
      irrigation. The main technique index was that irrigating water temperature should
      be 18-20 degrees C, irrigating period should be from phase IV to phase VII, and
      irrigating water depth should be 18-22 cm.

PMID- 14655365
TI  - [Photooxidation characteristics of super-hybrid rice "Liangyoupeijiu" and its
      parents].
AB  - With comparison of the differences of light absorption and active oxygen
      metabolism between super-hybrid rice "Liangyoupeijiu" and its parents, this paper
      provided a physiological foundation of matching and grouping for cultivating anti
      photooxidized hybrid rice. TPS-photosynthetic system and FMS2-fluorescence
      (Hansatech, UK) were used to respectively determine the photosynthetic rate and
      the chlorophyll fluorescence in the rice leaves that had been processed in
      artificial photooxidization. Meanwhile, the contents of chlorophyll, protein and
      malonaldehydic acid (MDA) as well as the activation of superoxide dismutase (SOD)
      and peroxidase (POD) were determined. The results showed that the photosynthetic
      rate of "Liangyoupeijiu" was 2.4% lower than that of its female parent, and 23%
      higher than that of its male parent. After eight days anti-photooxidization
      process, its chlorophyll content was higher than that of its female parent by
      33%, protein by 15%, initial photochemical efficiency by 30%, SOD by 32% and POD
      by 100%, while its photochemical quince coefficient was lower than that of its
      female parent by 9% and MDA by 50%. It showed that there was not much difference
      between the filial generation and its male parent. The super-hybrid rice
      "Liangyoupeijiu" was very efficient for solar energy utilization under the
      condition of photooxidization, and had outgrown its parents in the aspect of anti
      photooxidization.

PMID- 14655366
TI  - [Effect of iron oxide addition on hydrogen, carbon dioxide and methane geneses in
      paddy soil].
AB  - Paddy soil is an important contributor for atmospheric methane. The
      methanogenesis is related to the production of acetate, hydrogen and carbon
      dioxide during the decomposition of organic matter under anaerobic conditions. As
      electron acceptors, iron (III) oxides can effectively compete with electrons in
      the transformation of organic matter into methane. Its mechanism maybe relates to
      the consumption of H2 and CO2. After added ferrihydrite and lepidocrocite, the
      H2, CO2 and CH4 were determined during the anaerobic incubation of slurries at 25
      degrees C for 105 days. The results indicated that the addition of ferrihydrite
      and lepidocrocite could greatly decrease the concentration of H2, CO2 and CH4,
      and ferrihydrite had a stronger effect than lepidocrocite. In this system, the
      balance of organic-C was disturbed, CH4-C and CO2-C were reduced, but the CO3(2-)
      C fixed by slurry was greatly increased.

PMID- 14655367
TI  - [Integrated evaluation of eco-agricultural practices in Deqing County, Zhejiang
      Province].
AB  - Integrated index method was used to evaluate the practices of eco-agriculture in
      Deqing County in 1990-1998. The results showed that the integrated benefit,
      resources use, and ecological, economic and social benefits appeared a rising
      trend. The value of integrated benefit index in 1998 was 2.36 times of that in
      1990. The benefit index, however, also fluctuated in these years, which meant
      that the eco-agricultural system of Deqing County still had some problems to be
      resolved. Adjusting industry structure in rural areas, lessening pollution
      produced by rural industry, and improving stability of eco-agricultural system
      should be highlighted in the next stage.

PMID- 14655368
TI  - [Effect of enhanced UV-B radiation on competition among several plant species].
AB  - The effect of enhanced UV-B radiation (280-315 nm, approximating a 15% ozone
      layer reduction) on competitive interaction between spring wheat (Triticum
      aestivum) and wild oat (Avena fatua) was examined in the field. The density
      dependent mortality of both wheat and wild oat did not exhibit a significant
      difference between control and UV-B treatments. A relatively high degree of
      competitive stress enhanced the effect of UV-B stress on biomass reduction. Under
      UV-B enhancement, the relative competitive status of wheat in terms of total
      biomass and aboveground biomass increased, but decreased when based upon grain
      production. Shifts in competitive balance occurred with significant changes in
      total biomass, especially when plants grew at higher densities in monocultures
      and mixtures. There were different effects in direction and intensity of UV-B
      radiation on competition balance of the other three species pairs, but in
      general, the effect of UV-B was in favor of monocotyledonous. The results implied
      that total degree of competitive stress, especially interspecific competition,
      might be crucial to assess the effect of UV-B enhancement on agriculture
      ecosystem properly.

PMID- 14655369
TI  - [Effects of grazing, cutting and decapitating on grass populations on the
      artificial grassland in subtropical zone of China].
AB  - Studies on the effects of grazing, cutting and decapitating on grass populations
      on the artificial grassland in the subtropical zone of China showed that moderate
      grazing and cutting could increase the adaptability of Dactylis glomerata and
      Lolium prenn due to decapitating. Decapitating could rescind the apical dominance
      and reproduction growth of grass, and hence, the ecological effects of grazing
      and cutting on grass could be realized by decapitating, and the population
      density, caloric value and energy accumulation of Dactylis glomerata and Lolium
      prenn increased obviously. Apical dominance of grasses could lower the population
      density, energy accumulation and intra-population competitive ability.

PMID- 14655370
TI  - [Clonal growth of stoloniferous herb Potentilla anserina on degraded and non
      degraded alpine meadow soil].
AB  - The clonal growth of Potentilla anserina on degraded and non-degraded Kobresia
      humilis meadow soil was studied by a transplanting experiment in the field. No
      significant differences in numbers of stolons, height, and leave size per mother
      ramet were observed between the two soils, but the numbers of leaves per mother
      ramet, length and width of stolon, and spacer length were significantly
      different. There were more leaves per mother ramet, longer stolon and spacer, and
      wider stolon on degraded soil, where available nutrient was poor than in non
      degraded soil. Under degraded alpine meadow soil condition, the clonal plant
      species might produce much more photosynthetic product to support stolon growth
      by the increase of leave numbers per mother ramet, and the longer and wider
      stolon could intensify the foraging ability of the mother ramet that would
      benefit to daughter ramet. Both mother and daughter ramet of Potentilla anserina
      invested much more biomass to their underground part (root system) in non
      degraded soil to increase the survival rate of daughter ramet.

PMID- 14655371
TI  - [Optimizing of pastures grazing pattern with biomass growth and consumption
      models].
AB  - This paper discussed the biomass growth and consumption processes in grazed
      pasture ecosystems from a theoretical point of view, simulated the dynamics of
      these two processes with mathematical models, and analyzed the mechanism of
      ecological balance in pasture ecosystems from the perspective of these two
      processes. With the proposed biomass growth and consumption models, the dynamics
      of cumulative biomass consumption during one production cycle was simulated, and
      the optimal grazing strategies of pastures were proposed. The results could be
      valuable for pasture grazing management in practice.

PMID- 14655372
TI  - [Factors restricting growth of heterotrophic bacteria in the water body of West
      Lake, Hangzhou].
AB  - Restricting factors of bacteria growth were studied by pure culture and natural
      culture test. The results showed that organic carbon source available for
      bacteria was more important than (NH4)2SO4 and KH2PO4, while higher pH, and rich
      biomass of phytoplanktons and zooplanktons in the water restrained the growth of
      heterotrophic bacteria. Under natural culture experiment, Azotobacter increased
      after 0.5% glucose was added, and a lot of mildew grew after adding 0.5% glucose
      with 0.1% (NH4)2SO4 and 0.1% KH2PO4, while Pseudomonas enriched 30-57% after
      adding 0.01% beef extract. It was also showed that bacteria growth potentiality
      in natural water could reach to 10(5) cfu.ml-1.

PMID- 14655373
TI  - [Multianalysis between chlorophyll-a and environmental factors in Qiandao Lake
      water].
AB  - In this paper, the regression equation between chlorophyll-a (Chla) and some
      environmental factors was calculate by multiple stepwise regression, based on the
      monthly monitoring data in the Qiandao Lake from Jan. 1999 to Dec. 2000, and
      modified Carlson trophic state index for all the sampling sites was also
      analyzed. The results indicated that the spatial and temporal distribution of
      chlorophyll a in the sampling sites were varied strongly, the concentration of
      chlorophyll a in the Xin'an river changed from 50 mg.m-3 to 30 mg.m-3, but that
      in the lake was under 5 mg.m-3. The modified Carlson trophic state index (TSIM)
      for the sampling sites in southeast of the lake was under 37 (belonging to
      olligotrophic), and the others were under 53 (belonging to mesotrophic). In
      different sampling sites, the significant environmental affecting factors for
      chlorophyll a were different. However, the relationships between chlorophyll a
      and water temperature and total phosphorus were positive, and that between
      chlorophyll a and diaphaneity was negative.

PMID- 14655374
TI  - [Effects of rehabilitation of submerged macrophytes on nutrient level of a
      eutrophic lake].
AB  - The effects of rehabilitation of submerged aquatic vegetation on nutrient level
      of eutrophic waters were investigated by using large-scale enclosure system
      installed in a hyper-eutrophicated lake, Lake Donghu of Wuhan. The concentrations
      of total nitrogen (TN) and total phosphorus (TP) of the enclosures with
      artificially recovered submerged macrophytes were significantly lower than those
      of the macrophyte-free control enclosure and the lake water, and the TP of
      macrophyte enclosure was found to be around 0.1 mg.L-1 and relatively stable. The
      concentration of ammonia and nitrite of the macrophyte enclosures were lower than
      those of the control and the lake water. However, the nitrate concentrations did
      not differ among the various water bodies. It was demonstrated that re
      establishment of submerged macrophytes could efficiently reduce the nutrient
      level and thus control the overgrowth of the undesirable algae and improve water
      quality in the eutrophic lakes.

PMID- 14655375
TI  - [Sublethal effects of insecticides on fecundity of multicolored Asian ladybird
      Harmonia axyridis].
AB  - The effects of sublethal doses of 6 insecticides (imidacloprid, rotenone,
      fenvalerate, abamectin, pirimicarb and azadirachtin) on the fecundity of
      multicolored Asian ladybird Harmonia axyridis were determined respectively. The
      results showed that in all treatments, the daily average number of eggs per
      female ladybird was about 40-55. Ladybirds pretreated with imidacloprid by
      contact and feeding methods, and with rotenone by feeding method produced
      significantly fewer eggs, compared with control. But the accumulative oviposition
      of ladybirds pretreated with 6 insecticides at sublethal level was no significant
      differences, compared with untreated ladybirds. The hatching rates of the eggs
      laid by ladybirds pretreated with 6 insecticides by two methods were all lower
      than that of control. The accumulative survivals from egg to pupal stage of all
      treatments decreased significantly. The developmental duration from egg to pupa
      of those treated with imidacloprid by two methods and with fenvalerate by contact
      method prolonged significantly, while that of those treated with rotenone by two
      methods and with fenvalerate, abamectin, pirimicarb, and azadirachtin by feeding
      method shortened obviously, but that of those treated with rotenone and abamectin
      by contact method had no differences with control. After the eggs were immersed
      with sublethal concentrations of imidacloprid, rotenone, fenvalerate and
      abamectin, the successful hatching rates were all lower than that of control, and
      the development periods prolonged clearly. The 1st instar larval survival rates
      of those treated with fenvalerate decreased significantly, and the survivals from
      2nd instar larval to pupal stage also reduced to some extent. The total
      developmental duration of those treated with rotenone and fenvalerate prolonged
      significantly. These findings suggested that the effects of insecticides at low
      doses on the fecundity of ladybird were very complicated. The class, action mode,
      toxicity and exposure route of insecticides could affect the results of
      experiments.

PMID- 14655376
TI  - [Chaotic diagnosis of Nilaparvata lugens occurrence system].
AB  - It is estimated that there are nearly 20 million hectares of rice crop being
      infested by Nilaparvata lugens, with an annual loss of some half a million tones
      of grain. In order to study the properties and laws of Nilaparvata lugens
      occurrence system further, the time series data of Nilaparvata lugens occurrence
      from 1986 to 1998 collected in Taihu Lake District were analyzed by using the
      methods of autocorrelation function, power spectrum figure, phase trajectory
      figure, poincare section, and return map of chaos theory. The results indicated
      that Nilaparvata lugens occurrence system in Yangtze River valley area in China
      had an obvious chaotic property, even though there was some interference of
      random noises.

PMID- 14655377
TI  - [Landscape pattern of Nanjing urban-rural ecotone].
AB  - Landscape ecological characteristics of the urban-rural ecotone of Nanjing City
      were studied by using remote sensing and geographical information system (GIS)
      techniques. Two representative study regions with the same area were chosen in
      the eastern and southern part of the city. The urban-rural fringe of both east
      (URFE) and south region (URFS) can be divided into three zones: fringe-paraurban
      zone, transition zone and pararural zone. URFE was basically characterized by low
      landscape diversity, dominance and fragmentation. The forest patches in URFE had
      larger area and average perimeter, while their average fractal dimension, average
      stretched index and separated degree were lower. The average area of vegetable
      land and paddy land was larger than that of south region. URFS showed higher
      landscape diversity, dominance and fragmentation, more and higher density of
      patches. The area and the perimeter of water and architectural patches in URFS
      were also larger than that of URFE. The relationship between patch area and
      fractal dimension, stretched index and fractal dimension, patch number and area
      were discussed. The function and contributing factors of each type of patches,
      especially forestland, and the landscape characteristics and the ecological
      significance of corridors including road, river, and city wall of urban-rural
      fringe were also analyzed.

PMID- 14655378
TI  - [Effect of transgenic plants on biodiversity of agroecosystem].
AB  - The effect of transgenic plants on the biodiversity of agroecosystem is an
      important environmental issue. There are many researches in this field at home
      and abroad recently. This paper reviewed the advances of the researches based on
      three levels of biodiversity as genetic diversity, species diversity and
      ecosystem diversity. They included following aspects: the effect of insect
      resistant transgenic crops on target pest; the effect of herbicide-resistant
      transgenic crops on crops and wild weedy relatives; the effect of virus-resistant
      transgenic crops on virus; and the effect of transgenic crops on non-target
      organisms. This paper also discussed the effect of transgenic crops on soil
      ecosystem and crop genetic diversity. Their potential risks included uncontrolled
      flows of genes to wild relatives; development of herbicide, insect, and virus
      resistance in wild relatives; reduced crop genetic diversity; and adverse effects
      on organisms that were not pests, such as beneficial insects.

PMID- 14655379
TI  - [Origin of SARS from accelerated evolution of a virus by combined pollution].
AB  - The SARS virus origin which obviously differs from the theory of out-space origin
      and the theory of wildlife origin was theoretically discussed based on principles
      of pollution-evolution ecology, pathogenesis and infectant characteristics of
      SARS, and some relevant experimental evidence. It emphasizes on the fact that
      increasingly combined pollution in China provides a substantial basis for virus
      evolution. Gene recombination and fusion of more than one virus in ecosystems
      should take charge with the origin of a SARS virus. In particular, a common cold
      or influenza virus can acceleratedly changed into a superpower common cold or
      influenza virus through genetic mutation and gene recombination by increasingly
      combined pollution. This work can be useful for human beings to overcome SARS in
      theory.

PMID- 14655380
TI  - [Effect of plants on methane production, oxidation and emission].
AB  - The paper reviewed the role of plants in the processes of methane production,
      oxidation and emission in soils. It was the abilities of different plants to
      excrete the quantity and quality of root exudates that resulted in discrepancies
      of methane production among plants and in plant growing seasons. The oxygen
      magnitude of the downward transport through the plant aerenechyma, which, in
      turn, also acted as a conduit for methane from the soil to the atmosphere,
      affected endogenous methane oxidation capacity with plants and with plant growing
      seasons. Plant through changing amount and density of plant aerenchyma altered
      its ability to transport methane from soil to atmosphere. In addition to soil
      properties, flux and pattern of methane emission from soils largely depended on
      plant abilities to excrete exudates and oxygen, and transport methane in
      different plant growing seasons.

PMID- 14655381
TI  - [Effects of land use change on carbon storage in terrestrial ecosystem].
AB  - Terrestrial ecosystem is an important carbon pool, which plays a crucial role in
      carbon biogeochemical cycle. Human activities such as fossil fuel combustion and
      land use change have resulted in carbon fluxes from terrestrial ecosystem to the
      atmosphere, which increased the atmospheric CO2 concentration, and reinforced the
      greenhouse effect. Land use change affects the structure and function of the
      terrestrial ecosystem, which causes its change of carbon storage. To a great
      extent, the change of carbon storage lies in the type of ecosystem and the change
      of land use patterns. The conversion of forest to agricultural land and pasture
      causes a large reduction of carbon storage in vegetation and soil, and the
      decrease of soil carbon concentration is mainly caused by the reduction of
      detritus, the acceleration of soil organic matter decomposition, and the destroy
      of physical protection to organic matter due to agricultural practices. The loss
      of soil organic matter appears at the early stage after deforestation, and the
      loss rate is influenced by many factors and soil physical, chemical and
      biological processes. The conversion of agricultural land and pasture to forest
      and many conservative agricultural practices can sequester atmospheric carbon in
      vegetation and soil. Vegetation can sequester large amounts of carbon from
      atmosphere, while carbon accumulation in soil varies greatly because of farming
      history and soil spatial heterogeneity. Conservative agricultural practices such
      as no-tillage, reasonable cropping system, and fertilization can influence soil
      physical and chemical characters, plant growth, quality and quantity of stubble,
      and soil microbial biomass and its activity, and hence, maintain and increase
      soil carbon concentration.

PMID- 14655382
TI  - [Ecological adaptability and application safety of Epiblema strenuana as a
      biocontrol agent against ragweed].
AB  - Epiblema strenuana is the most important natural enemy against Ambrosia
      artemisiifolia, A. trifida and Parthenium hysterophorus. In this paper, its
      ecological adaptability and application risk as a biological agent against
      ragweed was analyzed and reviewed. Epiblema strenuana had a restrict host
      specificity, with all the field hosts belonging to Ambrosinae, and its selective
      risk on sunflower and chrysanthemum was less than 0.01 or/and zero (no risk). 15
      35 degrees C was the suitable temperature regimes for E. strenuana to develop,
      and lower constraint temperature could reach -8(-)-12 degrees C. The population
      size of this insect could increase 23 and 4 times on A. artemisiifolia, A.
      trifida and Xanthium sibiricum after each generation, respectively. In the field,
      the infected plants had an average of 20-30 galls per plant, and died with 5.2
      and 26 galls before and after rosette stage. The spread distance of this moth
      within 12 months after release was more than 100 km. It indicated that E.
      strenuana was an effective and safe agent for cereal and economic crops,
      ornamental plants, and indigenous natural enemy in the introduced region.

PMID- 14655383
TI  - [Construction and important factors analysis of natural life table of
      diamonthback moth, Plutella xylostella under pesticides treatment].
AB  - The natural life tables of diamonthback moth (DBM), Plutella xylostella under
      pesticides treatment were constructed, and the construction method of item
      "pesticide" was particularly discussed. The life tables indicated that the
      indices of population trend (I) under the treatment with 80% Dichlorvos EC 1000x
      and the contrast were 0.7796 and 1.4804, respectively, showing that Dichlorvos
      had some control on DBM. But, Dichlorvos had some effects on natural enemies of
      DBM. The decrease of parasitism rate at pupa stage was most obvious, which
      indicated that Dichlorvos had some effects of killing and wounding on the natural
      enemies of DBM.

PMID- 14655384
TI  - Every which way but loose.

PMID- 14655385
TI  - Frail safe.

PMID- 14655386
TI  - Acute concern.

PMID- 14655387
TI  - A gender for change.

PMID- 14655388
TI  - Analysis. What's the big idea?

PMID- 14655389
TI  - Corporacy in care.

PMID- 14655391
TI  - The HSJ interview: Sarah Mullally. Empower of good. Interview by Nick Edwards.

PMID- 14655392
TI  - Chewing the fat.

PMID- 14655393
TI  - Weight of expectation.

PMID- 14655394
TI  - Nurse-led NHS. Over to you.

PMID- 14655395
TI  - HSJ people. Alarm bells.

PMID- 14655396
TI  - Finance. Out for the count.

PMID- 14655397
TI  - Patient safety. The journey to safety.

PMID- 14655398
TI  - Patient safety. Safe and sound.

PMID- 14655399
TI  - Keep in step. Follow the seven steps to patient safety.

PMID- 14655400
TI  - Clarity begins at home.

PMID- 14655401
TI  - Hive of activity....

PMID- 14655402
TI  - The HSJ interview: Professor Mike Richards. On track. Interview by Sarah Grant.

PMID- 14655403
TI  - Clinical management. Where medicine meets management. Heart act to follow.
AB  - Areas taking part in the original CHD collaborative have seen a fourfold
      reduction in deaths from heart attacks. Improvements are based on more rigorous
      and accurate information gathering. The skills learned should cover the 10
      clinical domains of the new GP contract--and more.

PMID- 14655404
TI  - Mission position.
AB  - Many primary care trusts do not see sexual health as a priority, preferring
      simply to meet national targets. Genito-urinary medicine clinics do not have the
      capacity to attack waiting times. Rather than just a medical model, health
      promotion workers, youth and voluntary should work together.

PMID- 14655406
TI  - Law. Travellers' cheques.

PMID- 14655408
TI  - e-novation. Time to unwrap.

PMID- 14655407
TI  - HSJ people. Net worth.

PMID- 14655409
TI  - e-novation. Trouble in store.

PMID- 14655410
TI  - e-novation. Child in mind.

PMID- 14655411
TI  - e-novation. Carrot and slapstick.

PMID- 14655412
TI  - Building healthier relationships.
AB  - ProCure21 has been rolled out nationally with a fanfare of regional presentations
      and it took centre stage at the recent Healthcare Estates Conference in
      Harrogate. Evidence to date indicates that this innovative procurement process is
      going to be an unqualified success for both the buyers and sellers of
      construction services, says Andrew Percival, Alliance Development Manager, Taylor
      Woodrow ProCure21 Alliance. Taylor Woodrow is one of the 12 Principal Supply
      Chain Partners in the national NHS ProCure21 framework.

PMID- 14655414
TI  - Estate professionals must be adaptable.

PMID- 14655415
TI  - Will revolution bring chaos?
AB  - A waste revolution, potentially greater in impact than the changes in clinical
      waste disposal practices in the 1990s, is just over the horizon. There are many
      new initiatives and regulations relating to waste, its production, recycling and
      disposal. This article focuses on hazardous waste, a new category of waste with a
      much broader scope than the current special waste category. The volume of waste
      to be categorised as hazardous is expected to triple. One of the major reasons
      for change has occurred due to a long-running battle between the UK and other EU
      members about whether co-disposal of inert, biodegradable and hazardous waste in
      landfill sites is environmentally acceptable. The UK argued that co-disposal was
      acceptable but lost the argument. Consequently from July 2004 the EU Landfill
      Directive banning co-disposal will come into effect. According to the Government,
      this will mean that only 14 of the 182 commercial landfills that currently accept
      hazardous waste will continue to do so after July 2004. The expectation is that
      hazardous waste, such as electronic equipment, will require pre-treatment before
      landfilling. Meanwhile the landfill tax is expected to rise from 13 Pounds per
      tonne in 2002-03 to approximately 35 Pounds per tonne by 2007. In the near
      future, more waste will be classified as hazardous, it will cost much more to
      dispose of, waste management practices will need to change and the risk of
      breaking the law will increase. This article explains the actions that should be
      considered now to avoid chaos as the revolution takes place.

PMID- 14655416
TI  - Integrated maintenance management.

PMID- 14655417
TI  - Risk analysis highly valued.
AB  - It is felt that risk and vulnerability analysis is an excellent means of
      assessing and communicating risk and inconvenience related to extensive
      construction activities. The main reasons for this are: It uncovers the risks and
      inconveniences involved. Risk reducing and alert measures are identified.
      Preventive action and emergency plans are implemented. It is easy to learn. It is
      unbureaucratic. It promotes cross-professional communication. It distributes
      correct information very effectively.

PMID- 14655418
TI  - A vital campaign.

PMID- 14655419
TI  - Raising expectations in primary and community care.

PMID- 14655420
TI  - Managing risks.

PMID- 14655421
TI  - A complicated stress fracture of the femoral neck--a case report.
AB  - A case is presented of a stress fracture of the femoral neck complicated by
      complete fracture. Additional complications arose when the repaired fracture went
      on to non-union due to bending of the DHS screw, requiring revision surgery with
      a valgus osteotomy. The case is important because this type of stress fracture
      has previously been considered to be safe from risk of complete fracture. The
      failure of the operative treatment has implications for young patients treated
      similarly.

PMID- 14655422
TI  - Survival of the fittest? The scientific basis for the Royal Navy pre-joining
      fitness test.
AB  - The Royal Navy introduced a pre-joining fitness test to the selection procedures
      for RN Ratings from Summer 2003. The scientific basis for the test came from the
      present study to investigate if anthropometric and physical fitness measures
      predicted training failure. Fitness and anthropometric data from 1641 trainees
      were collected, together with their training outcome (i.e. pass or fail), during
      the period from September 2001 to March 2002. In addition, a retrospective
      interrogation of medical records identified those who reported any lower limb
      injuries. The overall rate of training attrition was 22%. Success in training was
      associated with: gender; age; physical fitness; and, in the case of females, Body
      Mass Index (BMI). The reported incidence of lower limb injury (LLI) was
      associated with: gender; physical fitness; and, for female trainees, BMI. The
      reported incidence of LLI was approximately 50% in the 'least-fit' female group
      compared to 10% in the 'most-fit' male group. 16% of females and 2% of males were
      considered 'unfit' (i.e. did not attain the prescribed run standards of 13 min 15
      s and 11 min 13 s respectively). 3% of trainees were considered 'obese' (a BMI >
      30 kg.m-2) whereas more than 25% were overweight (BMI > 25 kg.m-2). As a result
      of this work, selection candidates must now demonstrate a minimum standard of
      aerobic fitness prior to arrival at HMS Raleigh. The future impact of this
      selection measure on the reported incidence of lower limb injury and financial
      costs of training requires further investigation.

PMID- 14655423
TI  - Modelling the effectiveness of techniques for reducing heat strain in Royal Navy
      nuclear, biological and chemical cleansing stations' teams.
AB  - High temperatures, combined with wearing nuclear biological chemical (NBC)
      individual protective equipment (IPE), produce significant heat strain in
      personnel working in ships' NBC cleansing stations (CS) and limit the ability of
      ships to operate in a contaminated environment. This report reviews the potential
      solutions to this problem and concludes that only a method of actively cooling
      personnel will reduce heat strain and increase the number of people that can be
      processed through ships' NBC CS. Amongst the wide range of cooling equipment that
      might offer a benefit, only hand immersion in cold water and ice-vests are
      practically useful for use in NBC CS. To assess how effective these techniques
      are likely to be INM has modelled the thermal effects under environmental
      conditions expected in the CS when operating in a hot climate. The model
      predicted that hand immersion in cold water (10 degrees C) would be the most
      effective cooling method, providing that personnel were able to take regular rest
      periods to immerse the hands. If it is preferred that personnel in the CS be able
      to work continuously, then ice-vests would be effective. The safe total work time
      that can be achieved in a three hour period without a cooling intervention is
      approximately 72 minutes, regular rest periods must be taken throughout the three
      hour work period, to total of 108 minutes. Safe work times can be increased to 99
      minutes by using an ice-vest and 117 minutes by using hand immersion in 10
      degrees C water, with required rest times reduced accordingly, thereby increasing
      capacity of CS teams to decontaminate personnel.

PMID- 14655424
TI  - Testing the effectiveness of techniques for reducing heat strain in Royal Navy
      nuclear, biological and chemical cleansing stations' teams.
AB  - Nine personnel simulating the work of an NBC cleansing station (CS) in conditions
      expected in Middle Eastern waters had a limited work duration due to
      incapacitating heat strain. When the subjects were allowed five minutes rest
      periods after every 10 minutes of work, the endurance of seven of the subjects
      was limited to between 75-105 minutes due to heat strain and heat illness. By the
      point of withdrawal mean (SD) rectal temperature (Tre) had risen by 1.8 degrees C
      (0.4 degree C). The other two subjects were withdrawn earlier because they
      reached cardiac safety limits. When the hands were immersed (HI) in 10 degrees C
      water during the five minute rest periods heat strain was significantly lower (P
      < 0.01) and work endurance times were increased. One subject was withdrawn early
      on reaching cardiac safety limits, two on reaching Tre limits (39 degrees C) at
      105 minutes, and six subjects completed the 180 minute exposure with a final Tre
      of 38.4 degrees C (0.3 degree C). Using 'iced' (0 degree C) rather than 10
      degrees C water for HI further reduced heat strain (P < 0.01) and increased
      endurance times. Three subjects were withdrawn early on reaching cardiac safety
      limits, the remaining six completing the 180 minute exposure, with a final Tre of
      38.3 degrees C (0.5 degree C). Using an ice-vest (IV) in conjunction with HI
      further reduced heat strain (P < 0.01) and increased endurance times. Two
      subjects were withdrawn early on reaching cardiac safety limits, the remaining
      seven completing the 180 minute exposure, with a final Tre of 38.2 degrees C (0.8
      degree C) when 10 degrees C HI water was used, and Tre 38.0 degrees C (0.4 degree
      C) when 0 degree C HI water was used. There were no reports of finger numbness or
      loss of dexterity due to HI, and all personnel were able to remove their own
      individual Protective Equipment (IPE) without difficulty. It is expected that
      using HI will not reduce the ability to decontaminate or undress others. The HI
      technique and IV equipment should be introduced into the Fleet. 'Iced' water
      should be used in preference to 10 degrees C, although any water colder than 25
      degrees C will provide some benefit. The IVs increased torso girth and personnel
      should try them on (with frozen ice packs inserted) prior to their use and ensure
      that their protective clothing still fits, or obtain a larger size.

PMID- 14655425
TI  - Exercise destined glory.

PMID- 14655426
TI  - Views of a Far Eastern passage: colorectal surgery in Singapore.

PMID- 14655427
TI  - Overseas SpR4th year subspeciality training report August 2001 to August 2002.
AB  - These two attachments were in highly specialised fields of medicine and only
      loosely connected with anaesthesia. However, as a military anaesthetist, both of
      these areas are highly relevant. The jobs were of high quality from an
      educational and training perspective and were also allied with an increased
      amount of autonomy and responsibility appropriate to this stage of training.

PMID- 14655428
TI  - Facility profile. Chicago hospital can flex for change.

PMID- 14655429
TI  - Alternative energy. Hospitals explore the benefits of combined heat and power.

PMID- 14655430
TI  - Up to date. Maintaining your organization's state facilities license.

PMID- 14655431
TI  - Running hot + cold. Part 1: Proper boiler maintenance is a matter of safety.

PMID- 14655432
TI  - Running hot + cold. Part 2: Keeping a chilled water system operating efficiently.

PMID- 14655433
TI  - Device dangers. Complying with the JCAHO's patient safety goals for
      clinical/biomedical equipment.
AB  - A relatively new requirement of the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO) accrediation process is compliance with several
      National Patient Safety Goals (NPSGs) selected from the list of alerts by the
      JCAHO's Sentinel Event Alert Advisory Group.

PMID- 14655434
TI  - Disinfecting versus sanitizing. Selecting the right bleach makes all the
      difference when laundering hospital textiles.

PMID- 14655435
TI  - [Stroke: faster diagnosis, better therapy. Preserve nerves(cells)!].

PMID- 14655436
TI  - [What do baths and plants promise and deliver. Natural healing procedures are
      up].

PMID- 14655439
TI  - [World wide the highest radiation exposure. Is there too much roentgen in the
      German practices?].

PMID- 14655438
TI  - [New strategies against autoaggressive immune system. Is rheumatism to be
      healable soon?].

PMID- 14655440
TI  - [Losing weight as a countermeasure to diabetes, hypertension, stroke... The
      therapeutic potential is enormous].

PMID- 14655441
TI  - [Murnau comorbidity study on obesity in children and adolescents -- a call to
      prevention].
AB  - In children and adolescents, overweight must not be seen merely as a biological
      variant; rather, it is often associated with numerous health problems and
      sequelae. For this reason, obese children and adolescents should be carefully
      examined for the presence of the latter. To help the physician in this,
      guidelines for a rational diagnostic approach are available. Since an individual
      behavioral-therapeutic intervention frequently fails to produce a positive long
      term effect, and many physicians are compelled to initiate medication at an early
      stage, preventive measures directed at causal factors would appear crucial.
      Pediatricians, specialists in adolescent medicine and family doctors can make a
      useful contribution to the implementation of the various options for prevention.

PMID- 14655442
TI  - [New therapeutic options in obesity].
AB  - The basis for a therapeutic concept for obesity comprises specific measures aimed
      at changing inappropriate lifestyle habits (overeating, unsuitable diet,
      sedentary lifestyle) and psychological counseling (identification of bad eating
      habits, motivation, intensive coaching). Education by a physician on an
      individual or small-group basis, with emphasis on the practical implementation of
      fitness training (endurance and muscle building!), together with modification of
      the diet, has proved successful. In parallel with this, supportive anti-obesity
      medication makes a useful contribution to weight reduction and the control of
      risk factors. Evidence-based anti-obesity drugs such as sibutramine and orlistat
      facilitate the start of weight reduction, thus providing additional motivation of
      success, and support the long-term effect by stabilizing the weight loss. Health
      insurance carriers should, in future, selectively support evaluated and approved
      medication-based and non-medication-based weight-reduction programs, and
      reimburse the patient who has successfully participated in one.

PMID- 14655443
TI  - [Dietary supplements and functional food for weight reduction -- expectations and
      reality].
AB  - Looked at with scientific dispassion, much of the frequently aggressive
      advertising for slimming products must be considered to be dishonest and
      misleading. This applies, for example, to the "fat burner" carnitine or for
      chromium-containing preparations such as chromium picolinate, which in large
      doses have been shown to have detrimental effects on health. Products for which
      there actually is a scientific rationale all have minor weight-reducing effects,
      so that they must be considered to have at most an adjuvant role within the
      framework of evidence-based concepts for losing weight. Examples of alleged
      slimming substances that in reality can do no more than support weight reduction
      are the so-called medium-chain triglycerides (MCT) or caffeine, with the latter
      showing an effect vis-a-vis placebo only in combination studies with ephedrine.

PMID- 14655444
TI  - [Bradycardic arrhythmias. When do they become life threatening?].

PMID- 14655445
TI  - [Treatment of hypertension is inadequate. What are the reasons?].

PMID- 14655446
TI  - [Treatment of behavioral disorders in dementia with risperidone in
      psychogeriatric outpatients].

PMID- 14655447
TI  - [Pain therapy in rheumatism. After 65 years of age coxibs are the best choice].

PMID- 14655448
TI  - [Ask the patient with hypertension about dizziness and headache! High blood
      pressure in the morning is not a silent killer].

PMID- 14655449
TI  - [Chronic hepatitis C. Chances of healing good as never before].

PMID- 14655451
TI  - [Modern wound care in ulcus cruris. Less pain in changing of bandages].

PMID- 14655450
TI  - [After the numerous ergotamine preparations are on the way out. Migraine patients
      to change over to triptans].

PMID- 14655452
TI  - [Interview with Professor Kurt Baerlocher, St. Gallen. Hyperactive child -- does
      it depend on magnesium?].

PMID- 14655453
TI  - [Osteoporosis medications. Bisphosphonates exceed the others].

PMID- 14655454
TI  - [Early detection of COPD and erectile dysfunction. Here your communication talent
      is needed].

PMID- 14655455
TI  - [Heartburn].

PMID- 14655456
TI  - [Erosions, strictures, Barrett's esophagus? Investigate reflux thoroughly].

PMID- 14655457
TI  - [How does it function? Radioiodine therapy].

PMID- 14655458
TI  - [Angiotensin-converting enzyme inhibitors :from vasoactive drugs to
      cardiovascular prevention tools].
AB  - Abundant evidence showed that angiotensin-converting enzyme (ACE)-inhibitors
      reduce long-term cardiovascular morbidity and mortality rates in patients with
      heart failure and myocardial infarction. More recent studies revealed clinical
      benefits also in hypertensive patients with comorbidity and lead to an extension
      of clinical indications. Indeed in patients with severe hypertension differences
      between drugs are hardly detectable because the risk reduction is mainly related
      to the control of blood pressure values independent of the type of therapy.
      Conversely in the presence of comorbid conditions, especially in diabetics, the
      association of ACE-inhibitors with antihypertensive treatments proved its
      efficacy in reducing cardiovascular morbidity and mortality so that the role of
      mechanisms extending beyond blood pressure reduction can be postulated.

PMID- 14655459
TI  - [Doppler myocardial imaging in the evaluation of the athlete's heart].
AB  - Hemodynamic overload due to long-term training usually involves both left and
      right ventricles, inducing changes in cardiac structure such as an increase in
      internal cavity diameters, wall thickness and mass. Standard Doppler
      echocardiography has been widely used to identify the athlete's heart and to
      distinguish it from left ventricular pathologies. Pulsed Doppler myocardial
      imaging (DMI) extends Doppler applications beyond the analysis of cardiac blood
      flows to the measurement of myocardial wall motion. Recent reports have
      documented the usefulness of DMI in the evaluation of the athlete's heart. In
      particular, DMI analysis of trained subjects may represent a valid noninvasive
      tool in the following fields of application: 1) to assess differences in
      myocardial function in diverse forms of both physiological and pathological left
      ventricular hypertrophy; 2) to predict left ventricular performance during
      effort; 3) to analyze the effects of different training protocols on ventricular
      regional function; 4) to evaluate biventricular cooperation; 5) to detect
      myocardial dysfunction associated with pathological genotype in cardiomyopathies.

PMID- 14655460
TI  - [Myocardial interstitial fibrosis and diastolic dysfunction in hypertrophic
      cardiomyopathy].
AB  - Hypertrophic cardiomyopathy is an autosomal dominant disease characterized by
      asymmetrical left ventricular hypertrophy, myocyte disarray, interstitial
      fibrosis, and small vessel disease. More than 100 mutations in 10 genes, all
      encoding for sarcomeric proteins, have been identified as responsible for this
      disease. While the etiology of hypertrophic cardiomyopathy has been extensively
      elucidated, its pathogenesis is not completely understood. Mutated proteins are
      incorporated in the sarcomere and impair myocyte contractility. This probably
      triggers the compensatory local release of trophic factors, which influence the
      development of the typical anatomical features of the disease. Modifying genes or
      the effect of environmental or local factors is likely to play a role.
      Interstitial fibrosis is a morphological characteristic of hypertrophic
      cardiomyopathy and, increasing chamber stiffness, is an important determinant of
      diastolic dysfunction. Studies on transgenic animals with hypertrophic
      cardiomyopathy emphasize the role of interstitial fibrosis in this disease.
      Recently our group has shown that collagen turnover, evaluated through serum
      markers of collagen metabolism, is more active in patients with hypertrophic
      cardiomyopathy than in normal subjects and that patients with passive diastolic
      dysfunction accumulate collagen I. These studies are potentially relevant as they
      allow to assess the effects of therapy with cardioreparatory drugs.

PMID- 14655461
TI  - [Recent time trends of myocardial infarction rates in northern Italy. Results
      from the MONICA and CAMUNI registries in Brianza: 1993-1994 versus 1997-1998].
AB  - BACKGROUND: Previously reported time trends of myocardial infarction rates in the
      MONICA Brianza 35-64-year-old population showed a clear decline in coronary heart
      disease mortality, mostly attributable to concurrent reductions in myocardial
      infarction attack rates, and to a lesser extent in 28-day case fatality. The aims
      of this study were to estimate time trends in more recent years (up to 1997-1998)
      in the same population and in the same age range, and to assess the impact of
      myocardial infarction among 35-74-year-old residents, an age range never
      investigated before in Italy using standardized population-based registers.
      METHODS: The myocardial infarction register in the Brianza population was resumed
      in 1997-1998, adopting the same standardized methods for data collection and
      classification of suspect coronary events as the WHO MONICA project, including
      the age group 65-74 years in addition to age groups usually covered. Age-specific
      and age-standardized rates of validated coronary mortality rates, of attack
      rates, and incidence rates and of 28-day case fatality were calculated. Time
      changes were estimated as the difference in rates. RESULTS: In comparison to the
      rates among 35-64-year-old residents, the 35-74 age-standardized rates of
      coronary event mortality in the biennium are more than 3 times higher in women
      and more than twice in men. Similarly, the attack and incidence rates increased
      respectively from 243 to 381 and from 197 to 292 per 100,000 in men, from 38 to
      107 and from 33 to 87 per 100,000 in women. Statistically significant reductions
      are observed in coronary death rates, myocardial infarction attack rates and 28
      day case-fatality rates between 1993-1994 and 1997-1998 in men. Analogous but not
      statistically significant changes are reported for women. CONCLUSIONS: In the
      Brianza MONICA population in the second half of the 1990s, coronary event death
      rates continued to decrease. In contrast with trends observed in previous years,
      the prominent quote of the reduction is attributable to case-fatality rates in
      the acute phase.

PMID- 14655462
TI  - [The SEOT-Urbe project:an observational study on the cardiovascular profile of a
      young population living in the Roman suburb].
AB  - BACKGROUND: Although several observational studies regarding clinical aspects of
      different populations have been performed, information about the cardiovascular
      profile and the lifestyle of young Italian people is poor. METHODS: A group of
      physicians working in the Roman area visited a population of outpatients aging
      between 20 and 50 years, with a medical history characterized by the absence of
      cardiovascular events. They collected information about the prevalence of
      cardiovascular risk factors, lifestyle, and the number of medical and
      instrumental controls performed by each patient. RESULTS: 5581 consecutive
      patients (2795 males, 2786 females, mean age 36 +/- 8 years) were included in
      this study. They were living in three different areas of the Roman suburb: civic
      zone, rural area, and seaside. At least one cardiovascular risk factor was
      observed in 4825 people (86.5%). Moreover 549 people (9.8%) reported more than
      three risk factors. Physical inactivity resulted the most frequently found risk
      factor; indeed its prevalence is high in every subgroup of patients, regardless
      of gender or geographical distribution. Regular medical controls are performed by
      2774 people (49.7%), most of them being visited by general practitioners; 288
      people (5.2%) complain of symptoms like dyspnea or palpitations. Cardiovascular
      therapy is taken more frequently than non-cardiovascular one (13.3 vs 3.7%). Very
      few instrumental exams (electrocardiogram, echocardiogram, physical stress test)
      show alterations. The analysis of the lifestyle and cardiovascular risk profile
      of people living in the different areas failed to show any significant
      differences. CONCLUSIONS: Despite the young age of the population, a great number
      of people show an increased cardiovascular risk profile and report a potentially
      dangerous lifestyle. The need for a primary prevention policy turns up in order
      to avoid the occurrence of as more expected cardiovascular events as possible.

PMID- 14655463
TI  - [Intracoronary beta-radiotherapy in high-risk in-stent restenosis. Prospective
      results of a single center registry].
AB  - BACKGROUND: The aim of the study was to evaluate, on single center prospective
      data, long-term angiographic and clinical results of intracoronary beta (32P)
      brachytherapy in "real world" patients with high-risk in-stent restenosis
      lesions. METHODS: Sixty-nine consecutive patients (77 lesions) with high-risk in
      stent restenosis (mean lesion length 30.3 +/- 16.1 mm, pattern III-IV 57.2%,
      diabetes 33.3%) treated with percutaneous dilation procedures and beta-radiation
      therapy, underwent 7-month clinical and angiographic follow-up. RESULTS: One
      patient (1.4%) presented with procedural non-Q wave myocardial infarction. At a
      mean follow-up of 7 +/- 1.5 months, death was observed in 1 patient (1.4%) and
      non-Q wave myocardial infarction in 3 (4.3%) (in 2 patients, who prematurely
      discontinued antiplatelet therapy, caused by late coronary thrombosis). Seven
      month binary angiographic restenosis occurred in 20 lesions (25.9%) (in-stent
      restenosis 11.6%). Target lesion and target vessel revascularization occurred in
      20 (28.9%) and 21 (30.4%) patients. At follow-up only 12 (17.3%) patients
      presented with CCS class III-IV angina. After intracoronary beta brachytherapy
      angiographic restenosis occurred regardless of the vessel size, lesion length and
      ostial location. On the contrary a high restenosis rate was documented in
      obstructive lesions. CONCLUSIONS: As applied in routine clinical practice,
      radiation therapy is safe and effective in the treatment of high-risk in-stent
      restenosis. In spite of all that, total occlusion at baseline predicts late
      angiographic restenosis.

PMID- 14655464
TI  - [Amiodarone-induced thyrotoxicosis: case report and review of the literature].
AB  - We report a case of amiodarone-induced thyrotoxicosis, and a broad review of the
      literature. Amiodarone is a drug widely used in cardiovascular medicine. Since it
      is iodine-rich, it may cause changes in thyroid function tests in some patients
      under chronic treatment. In 14-18% of amiodarone-treated patients, there is overt
      thyroid dysfunction (hypothyroidism or thyrotoxicosis). We here describe
      thyrotoxicosis, which can be distinguished in two subtypes differing in
      pathogenesis and treatment. Type I is primarily related to an excess of iodine
      induced thyroid hormone synthesis in an abnormal thyroid gland, and the main
      medical treatment consists of the simultaneous administration of thionamides and
      potassium perchlorate. Type II is due to amiodarone-related destructive
      thyroiditis and glucocorticoids are therapy of choice. Mixed forms frequently
      exist. Due to the low thyroidal iodine uptake, radioiodine therapy is usually not
      efficacious. Surgical treatment can be performed in cases resistant to medical
      therapy.

PMID- 14655465
TI  - [ A rare complication of thrombolytic therapy: spinal epidural hematoma. A case
      report ].
AB  - Spinal epidural hematoma is a rare complication of thrombolytic therapy (only 9
      cases described in the literature). We report the case of a 59-year-old female
      with hypertension, admitted to the coronary care unit for acute inferior
      myocardial infarction and treated with tissue-type plasminogen activator 100 mg
      in 90 min, intravenous heparin 25,000 U, aspirin 100 mg, and metoprolol 50 mg
      orally once daily. On the third day she suffered from sudden and violent dorsal
      pain, followed 22 hours later by paraplegia. Magnetic resonance imaging showed a
      large posterior spinal epidural hematoma, with compression and anterior
      dislocation of the spinal cord. The patient underwent neurosurgery. After 1 year,
      she still cannot walk. In patients treated with thrombolytic therapy and
      presenting with sudden and violent spinal pain, the physician should take into
      consideration the diagnosis of epidural hemorrhage. Early neurosurgery can save
      the patient and facilitate neurological recovery.

PMID- 14655466
TI  - [What future for the intensive coronary care unit without interventional
      hemodynamics?].

PMID- 14655467
TI  - [Brugada syndrome: electrocardiographic trap simulating an acute antero-septal
      myocardial infarct].

PMID- 14655468
TI  - [Difficult search for etiology of urticaria. Stressful hives].

PMID- 14655469
TI  - [Anemia--infertility--dermatosis--osteoporosis. Sequelae of diagnosed celiac
      disease].

PMID- 14655470
TI  - [Analgesia with opioids. Pain therapy is standardized care].

PMID- 14655471
TI  - [Preoperative radio-chemotherapy in rectal carcinoma. Forestalling colostomy].

PMID- 14655472
TI  - [Dual therapy of onychomycoses. Only Schwaben Province physicians also think of
      costs].

PMID- 14655473
TI  - [Cabbage leaf wrap. White cabbage works better].

PMID- 14655474
TI  - [Fox tapeworm. Is there a risk also in our cities? (interview by Dr. Th.
      Meissner)].

PMID- 14655475
TI  - [Improved management concepts in psychiatry. Decisive value for the fate of our
      patients].

PMID- 14655476
TI  - [From patient screening to management list in suicide risk. Practical guideline
      for dealing with depression].
AB  - Despite the fact that effective treatments are available, only a minority of
      patients with depressive disorders receive appropriate care. The reasons are to
      be sought at the level of primary medical care, in public attitudes towards
      mental illness, in the patients themselves, and structural aspects of the health
      care system. A range of structural elements may be helpful in improving patient
      management at the primary care level--including the screening instrument WHO-5,
      recommendations for educating the patient about his/her illness, a list of
      measures aimed at preventing suicide, a plan of action and criteria for the
      interface family doctor/specialist, and support for the patient in coping with
      his/her problem.

PMID- 14655477
TI  - [Neuroleptics--psychotherapy--psychiatric social work. In schizophrenia help is
      needed from many sides].
AB  - Schizophrenic disorders require a complex, multidimensional treatment strategy.
      Throughout the entire course of the illness, psychopharmacologic,
      psychotherapeutic and psychosocial therapeutic measures must be integrated within
      an overall management plan. Although treatment planning should be orientated to
      the needs and expectations of the patient, current therapeutic guidelines must
      also be taken into account. Management decisions are based on such central
      questions as the patient's ability to cope with the requirements of daily life,
      or the attitude to the illness of the patient and family members. Inpatient
      treatment concepts include, in addition to pharmacotherapy, a cognitive
      behavioral therapeutic program. In the outpatient setting, the question as to
      supportive rehabilitation measures and social integration aids needs to be dealt
      with.

PMID- 14655478
TI  - [New stipulations for rehabilitation of mentally ill. Will return to normal life
      be facilitated?].
AB  - Current changes in the laws pertaining to mental disorders are mainly concerned
      with the redefinition in the Sozialgesetzbuch IX (SGB IX) [Social Law] of the
      term "disability", and the forthcoming introduction of the International
      Classification of Functioning, Disability and Health (ICF). Accordingly, the
      rehabilitation of the mentally disturbed will be based on an integrative bio
      psychosocial treatment concept, which--in parallel with curative therapy--right
      from the beginning envisages measures aimed at reintegration of the patient into
      daily/occupational life. On the basis of the ICF, all patients with mental
      disorders of more than 6 months' duration may be classified by the medical
      services of the health insurance carriers as being in need of rehabilitation.
      Appropriate care-related structures in psychiatric and psychosomatic areas are to
      some extent already available.

PMID- 14655479
TI  - [Heart failure, skin manifestations, enlarged hilar lymph nodes. Is it
      sarcoidosis?].
AB  - Sarcoidosis is defined as a multisystem disease of unknown genesis that affects
      in particular the middle-aged. In 80% of the cases, the acute form is associated
      with pulmonary manifestations, and in the majority of patients clears up--even in
      the absence of treatment--with no sequelae. The chronic version is characterized
      by the development of multiple pulmonary granulomas and progressive fibrosis.
      Subsequently, emphysema, cor pulmonale and right heart insufficiency develops.
      Almost 50% of chronic sarcoidosis patients have cardiac involvement with
      arrhythmias, heart block and the clinical picture of a cardiomyopathy, which in
      many cases leads to death--acutely (sudden cardiac death) or over the longer
      term. In manifest disease, treatment with steroids should be initiated and
      continued over a year. Conduction disorders require the implantation of a
      pacemaker.

PMID- 14655480
TI  - [Patient, 50, with chronic hepatitis C genotype 1 infection. Therapeutic success
      despite poor prognosis].

PMID- 14655481
TI  - [Prospective treatment study of irbesartan. Diabetic kidneys regain function].

PMID- 14655482
TI  - [Job-related discussions, professional politics, wine sampling. Are you included
      in quality circles as well?].

PMID- 14655483
TI  - [My anger at the system].

PMID- 14655484
TI  - [TNF-alpha antagonist in rheumatoid arthritis. Joint destruction can be
      controlled].

PMID- 14655485
TI  - [Beta blocker in heart failure. A little is better than nothing].

PMID- 14655486
TI  - [Insulin sensitizers is now approved as monotherapy as well. Lowering blood
      pressure with added effects].

PMID- 14655487
TI  - [Critical evaluation of indications for lipid reduction. Cholesterol value
      updated--risk counts (interview by Dr. Kirsten Westphal)].

PMID- 14655488
TI  - [Insufficient calcium and vitamin D3. Malnutrition as fracture risk factor].

PMID- 14655489
TI  - [Myocardial infarct, smoker's leg, dementia. Is homocysteine the culprit?].

PMID- 14655490
TI  - [Dietary management of lipid disorders. Plant oil protects hearts of diabetic
      patients].

PMID- 14655491
TI  - [Heart failure therapy. Cheap can become expensive].

PMID- 14655492
TI  - [Angina, dyspnea and constipation. Hepato-diaphragmatic interposition of the
      colon (Chilaiditi syndrome)].

PMID- 14655494
TI  - [Sweating against cardiac death. What training is needed to prolong life?].

PMID- 14655493
TI  - [Paresthesia of the leg].

PMID- 14655495
TI  - [Total cardiovascular risk. When is a medication prophylaxis meaningful].

PMID- 14655496
TI  - [Contribution of healthy nutrition. Coronary disease prevention with fish fillet
      and walnut oil].

PMID- 14655497
TI  - [Stubborn icterus inspite of opening of hepatic stenosis. Nephropathy discloses
      systemic disease].

PMID- 14655498
TI  - [With obscure symptoms always at the physician's. Is the "disease" of the child
      an invention of the mother?].

PMID- 14655499
TI  - [The holy Doctor of Moscow. Lew Kopelew has erected a monument to him].

PMID- 14655500
TI  - [Inhalation steroids in COPD: of value only for asthma patients!].

PMID- 14655501
TI  - [Clarifying chronic diarrhea. I. Drug-induced side effect and malabsorption].

PMID- 14655502
TI  - [Medication-related diarrhea].
AB  - Numerous medications can trigger diarrhea. In some cases it is a common side
      effect, and the relationship is evident (e.g. acarbose, somatostatin analogs and
      antibiotics). When diarrhea does occur, the therapeutic benefit of the drug
      should be weighed against the negative results of the side effect. If
      pseudomembranous colitis is suspected, prompt action is required, since a fatal
      outcome cannot be excluded. A particular challenge is a suspected drug
      association in a multimorbid patient taking several drugs, each associated with
      an only low diarrhea risk. In such a case, it may be necessary to discontinue
      drugs consecutively, or to replace a drug by another, until the diarrhea ceases,
      without lessening the effectiveness of the treatment.

PMID- 14655503
TI  - [Chronic diarrhea in malabsorption].
AB  - Chronic diarrhea with malassimilation is a symptom of numerous diseases ranging
      from celiac disease to lactate intolerance to chronic inflammatory bowel disease.
      Accordingly, they require an arsenal of diagnostic options. Clarification of the
      situation involves history-taking, a clinical examination, orientating and
      specific laboratory investigations, and imaging procedures, in particular
      ultrasound and endoscopy. Function tests such as the xylose-tolerance test, the
      H2 breath test or the various pancreas function tests are available as adjunctive
      options where indicated.

PMID- 14655504
TI  - [Tricky differential diagnosis: peri-oral inflammation].

PMID- 14655505
TI  - [Efficacy and tolerability of gabapentin in the treatment of patients with
      neuropathic pain. Results of an observational study involving 5620 patients].

PMID- 14655506
TI  - [Selective aldosterone blocking in heart failure. Eplerenone reduces the risk
      after infarction].

PMID- 14655507
TI  - [Aldosterone blocking -- a rediscovered therapy principle].

PMID- 14655508
TI  - [New medication for osteoporosis. To further increase instead of braking
      reduction].

PMID- 14655509
TI  - [Fast and strong lowering of pressure. The newest sartan has passed the practice
      test].

PMID- 14655510
TI  - [No medication for COPD patients who do not stop smoking? "Fat diabetics are
      treated, too"].

PMID- 14655511
TI  - [Extended oral anticoagulation. "Self-managers" live with less risk].

PMID- 14655512
TI  - [Modern antihistaminics against allergic rhinitis. Better breathing without side
      effects].

PMID- 14655513
TI  - [Question mark -- the aorta].

PMID- 14655514
TI  - [Cause of yearly 28 million lost days. Weather sensitivity cripples the
      workforce].

PMID- 14655515
TI  - [24-hour ph-metry of the esophagus].

PMID- 14655516
TI  - The variable but inevitable loss of beta cells in overt type 1 diabetes.

PMID- 14655517
TI  - The severity of clinical presentation of type 1 diabetes in children does not
      significantly influence the pattern of residual beta-cell function and long-term
      metabolic control.
AB  - AIM: The purpose of the present study was to compare relationships between the
      clinical presentation of type 1 diabetes in children and residual beta-cell
      secretion and long-term metabolic control. METHODS: This retrospective study was
      conducted in 66 diabetic children with age at diagnosis ranging from 0.7 to 14.8
      yr. The patients showed contrasting characteristics at diagnosis: either diabetic
      ketoacidosis (DKA) (group 1, n = 29) or absence of metabolic derangement (group
      2, n = 37) associated with marked (group 2A, n = 12) or mild hyperglycemia (group
      2B, n = 25). A regular follow-up was available for at least 10 yr (10-32 yr) in
      all cases and for 20 yr in 23 cases. C-peptide levels were measured from
      diagnosis and thereafter at intervals for the first years of disease until
      becoming permanently undetectable. RESULTS: C-peptide levels at diagnosis were
      undetectable in about 20% of the cases both with and without DKA. C-peptide
      levels at diagnosis, the duration of measurable C-peptide levels and the maximum
      value found during follow-up were not significantly different in the three groups
      and were not correlated with glycated hemoglobin (GHb) calculated throughout the
      whole period. No differences were found between the groups of patients concerning
      GHb values and insulin dose at 10, 15 and 20 yr of disease. The patients of group
      2A, characterized by an extremely high glycemic level without ketoacidosis, had a
      significantly higher prevalence of HLA DR3/4 heterozygosity. CONCLUSIONS: The
      severity of clinical presentation at diagnosis does not significantly influence
      residual beta-cell function, and long-term metabolic control.

PMID- 14655518
TI  - Aberrant monocyte prostaglandin synthase 2 (PGS2) expression in type 1 diabetes
      before and after disease onset.
AB  - METHODS: We examined monocyte prostaglandin synthase 2 (PGS2/COX2) expression in
      individuals at risk for or with type 1 diabetes including: (i) 58 established
      type 1 and 2 diabetic patients; (ii) 34 autoantibody positive (AA+) children and
      adults; (iii) 164 infants and young children with insulin-dependent diabetes
      mellitus (IDDM) susceptibility human leukocyte antigen (HLA) alleles; and (iv) 37
      healthy control individuals, over a 5-yr period. RESULTS: Established type 1
      diabetic patients (1 month to 30+ yr post-disease onset) had significantly higher
      PGS2 expression than healthy controls; by contrast, insulin-treated type 2
      diabetic patients had significantly lower PGS2 expression than healthy controls.
      Longitudinal studies of AA+ subjects at risk for type 1 diabetes indicated that
      73% (11/15) of individuals who developed this disease during the study period
      expressed high levels of PGS2 prior to or after onset. We also found high level
      PGS2 expression in genetically at-risk infants and young children that correlated
      with having a first-degree relative with type 1 diabetes, but not with age,
      gender, or HLA genotype. In this population, high level PGS2 expression coincided
      with or preceded autoantibody detection in 30% (3/10) of subjects. CONCLUSIONS:
      These findings suggest that high level monocyte PGS2 expression, although subject
      to fluctuation, is present in at-risk subjects at an early age and is maintained
      during progression to and after type 1 diabetes onset.

PMID- 14655519
TI  - Relationship between glycemic control, ethnicity and socioeconomic status in
      Hispanic and white non-Hispanic youths with type 1 diabetes mellitus.
AB  - OBJECTIVES: To determine if there is a disparity in glycemic control between
      Hispanic and white non-Hispanic children and adolescents with type 1 diabetes
      mellitus (DM) and to delineate the factors associated with glycemic control in
      these populations. STUDY DESIGN: This cross-sectional study included 183 youths
      with type 1 DM (99 white non-Hispanics and 84 Hispanics) and their
      parents/guardians cared for in a well-defined, private pediatric endocrine
      diabetes clinic, where the same physician and diabetes educators treat all
      patients. The youths were invited to participate if they had been diagnosed with
      diabetes at least 3 months before the study and were < 21 yr of age. Self-report
      questionnaires and chart reviews were used to assess individual familial and
      sociodemographic variables. OUTCOMES MEASURED: Mean hemoglobin A1c (HbA1c)
      levels, compliance with home monitoring of blood sugar, level of parental
      supervision of treatment, and socioeconomic status of Hispanic and white non
      Hispanic families in the study. RESULTS: Hispanic youths with type 1 DM were in
      poorer metabolic control than their white non-Hispanic counterparts (0.45%
      difference in HbA1c levels, p = 0.02). Hispanic youths exhibited lower compliance
      with home monitoring of blood sugar but their parents reported greater
      supervision of their diabetes treatment. Hispanic families were found to have
      significantly lower income, rate of health insurance, father's educational
      attainment, and mother's educational attainment. Lower family socioeconomic
      status, but not ethnicity or educational attainment of parents, was associated
      with a significantly higher HbA1c, regardless of ethnicity. CONCLUSIONS: This
      study suggests that Hispanic youths with type 1 diabetes may be at greater risk
      for poor glycemic control because of their lower socioeconomic status rather than
      their ethnicity.

PMID- 14655520
TI  - Barriers to the treatment of adolescent type 2 diabetes--a survey of provider
      perceptions.
AB  - OBJECTIVE: Type 2 diabetes mellitus (T2DM) is increasingly common among children
      and adolescents. However, achievement of good metabolic control has been
      difficult in this population. The aim of this study was to survey pediatric
      endocrine and diabetes specialists regarding the issues they consider to be
      barriers to successful treatment of adolescent T2DM. METHODS: An electronic
      questionnaire was administered to 220 physicians and nurses attending a
      conference on pediatric diabetology in 2001. RESULTS: The issues that were most
      strongly perceived as barriers to successful treatment of adolescents with T2DM
      were prevalence of high-risk lifestyle in other family members (98%), lack of
      immediate risk to life reducing patient motivation (89%), lack of guidelines
      regarding optimal treatment (73%), prevalence of behavioral and/or psychiatric
      disorders (71%), and cultural/language barriers (65%). The survey also revealed
      that in the majority of clinics, T2DM education programs were not designed
      specifically for type 2 patients nor delivered by a specifically trained
      education team. Furthermore, despite the fact that cultural and ethnic
      differences were identified as important barries to care, educational materials
      designed for particular racial and cultural groups were used in only 37% of the
      clinics. CONCLUSIONS: This survey identifies a number of areas perceived by
      clinicians to be significant barriers to successful treatment of T2DM in
      adolescent patients. Given the multiple challenges identified by the survey,
      programs addressed specifically to the characteristics of adolescents with T2DM
      will be necessary, including materials appropriate to the developmental stage and
      ethnic background of patients.

PMID- 14655521
TI  - Rhabdomyolysis in diabetic ketoacidosis.
AB  - Rhabdomyolysis is a potentially lethal disorder, characterized by elevated serum
      concentrations of creatine kinase (CK) due to skeletal muscle injury. In this
      paper a patient with diabetic ketoacidosis (DKA) is reported who developed
      rhabdomyolysis (maximum CK level, 37,700 U/L; normal, < 170 U/L), anemia (6.2
      g/dL) and thrombocytopenia (16,000/microL). This combination of rhabdomyolysis
      with anemia and thrombocytopenia has not yet been reported in DKA. The pathogenic
      mechanism leading to rhabdomyolysis in DKA remains unsettled. From the literature
      it seems that those patients who develop rhabdomyolysis have very high glucose
      levels and a high osmolality on admission. Low phosphate levels can play a role
      as well. The etiology of anemia and thrombocytopenia in our patient remains
      obscure. Intravascular hemolysis could not be demonstrated but intramedullar
      hemolysis, due to osmolar shift or hypophosphatemia, cannot be excluded. A review
      of the literature data revealed that rhabdomyolysis is not so uncommon in DKA.
      However, to obtain incidence data in children, prospective studies are necessary.

PMID- 14655522
TI  - Adiponectin/Acrp30, an adipocyte-specific secretory factor: physiological
      relevance during development.
AB  - Adiponectin/Acrp30 is a fat cell-specific secretory product. The convergence of
      results from epidemiological, pharmacological and genetic studies over the last 2
      yr has highlighted the important role that this multimeric protein complex plays
      in the context of insulin sensitivity. While the exact mechanism of action has
      not been elucidated, it is clear that adiponectin has insulin-sensitizing effects
      on both liver and muscle. The important role that adipose tissue plays in energy
      homeostasis as a storage compartment for triglycerides has been appreciated for a
      long time. The identification of leptin as a key hormone involved in central
      control of energy metabolism suggested that adipocytes also use polypeptide
      hormones to influence metabolic processes at distant sites. The recent progress
      made towards the characterization of the physiological role of adiponectin
      highlights the important role of adipose tissue as an endocrine organ and its
      central role in the fine-tuning of hepatic and muscle insulin responsiveness.

PMID- 14655523
TI  - Prevention of type 2 diabetes in young people: a theoretical perspective.
AB  - Type 2 diabetes in youth is an increasing public health concern, especially in
      certain minority populations. The current paper consists of four sections. First,
      we establish the significance of the problem by presenting an overview of
      epidemiological and physiological evidence. Second, we discuss behavioral issues
      relevant to the prevention of type 2 diabetes in youth. Third, a qualitative
      review of existing prevention interventions specific to type 2 diabetes in youth
      is presented. Results suggest that modest improvements in social cognitive,
      dietary, and exercise outcomes are possible with diabetes intervention studies,
      although beneficial changes are difficult to sustain over the long term. Although
      theoretical frameworks are not always explicit, most studies have utilized
      elements of the social cognitive theory. Less attention has been paid to
      sociocultural and community organization variables. Finally, the paper discusses
      issues of risk definition and intervention sustainability, and presents a
      comprehensive, theoretically diverse model for the prevention of type 2 diabetes
      in youth. In summary, we suggest that theories of the natural history and
      pathophysiology of type 2 diabetes are important to identify modifiable risk
      factors, while theories of behavioral change are essential to modify the risk
      factors identified. The combination of sound physiological and behavioral
      theories should form the basis of prevention intervention design. In addition, an
      ecologic approach that takes into consideration the dynamic interactions of
      personal, social, and environmental factors would best promote the long-term
      adoption of healthful behaviors in a supportive, meaningful, and personally
      enjoyable context.

PMID- 14655524
TI  - Results of continuous glucose monitoring by GlucoWatch Biographer in a cohort of
      diabetic children and adolescents under real-life conditions.

PMID- 14655525
TI  - How should we interpret "real life" conditions.

PMID- 14655527
TI  - Euphemistic codes and tell-tale hearts: humane assistance in end-of-life cases.

PMID- 14655526
TI  - Informed consent to the medical treatment of minors: law and practice.

PMID- 14655528
TI  - Students, urinalysis & extracurricular activities: how Vernonia's aftermath is
      trampling fourth amendment rights.

PMID- 14655529
TI  - "The original sexist sin": regulating preconception sex selection technology.

PMID- 14655530
TI  - Statement on motion sickness.

PMID- 14655531
TI  - [Does problem-based learning solve the problems of medical education?].

PMID- 14655532
TI  - [Capsule endoscopy--new light for the investigation of small bowel].

PMID- 14655533
TI  - [Early treatment of asthma is important--the evidence gets stronger].

PMID- 14655534
TI  - [Multiple sclerosis in a female patient].

PMID- 14655535
TI  - [Treatment of transsexuals].

PMID- 14655536
TI  - [Dengue fever--an increasing global problem and illness of Finns traveling to
      exotic countries].

PMID- 14655537
TI  - [Intravenous fentanyl in obstetrical analgesia].

PMID- 14655538
TI  - [Assessing the coxibs].

PMID- 14655539
TI  - [Profile of chronic insomnia].

PMID- 14655540
TI  - [Stumbling gait].

PMID- 14655541
TI  - [Joint pain in a young woman].

PMID- 14655542
TI  - [She who nearly took her bed and walked].

PMID- 14655543
TI  - [Cardiorespiratory impact of overweight].

PMID- 14655544
TI  - [Heart and nutrition: which fatty acids for which cardiac function?].
AB  - Cardiovascular risk factors are often related to diet and the dietary fatty acids
      play a leading role quantitatively and qualitatively. In addition to the
      demonstration of the beneficial properties of n-3 PUFA on the development of
      atherosclerosis, there is a growing body of experimental evidence on the
      implication of n-3 PUFA in the regulation of cardiac function because of cardiac
      enrichment with n-3 PUFA to the detriment of arachidonic acid. The antiarrhythmic
      effect of these PUFA has been demonstrated in several animal species, the
      positive results of the GISSI-prevenzione study being partially associated with
      this property. This effect is related to the presence of DHA in cardiac
      phospholipids but the molecular mechanism is poorly understood. Moreover, the
      presence of DHA in the membranes decreases the production of cAMP induced by a b
      adrenergic stimulation. This characteristic related to the interaction between
      the protein receptor complex and its environment provokes effects similar to
      those of a betablocker specifically due to the presence of DHA and not to the
      decrease in arachidonic acid. Finally, n-3 PUFA induce a reduction of cardiac b
      oxidation and oxygen consumption in the animal. This effect, mild undr
      physiological conditions, manifests itself during post-ischaemic reperfusions as
      an improvement of metabolic recovery and ventricular function. In conclusion, the
      relationship between the heart and fatty acids will change because of the
      increasing incidence of cardiac failure associated with a chronic catabolic
      state. Daily dietary PUFA, in particular the n-3 forms, is insufficient,
      especially when a hypertrophic heart has to increase its membrane mass. In view
      of the positive effects of a high BMI on morbi-mortality of cardiac failure,
      nutrition and cardiology may have to reinforce their relationship in the short
      term.

PMID- 14655545
TI  - [Nutritional epidemiology of coronary disease].
AB  - The nutritional epidemiology of coronary disease is complex because nutrition is
      composed of a large number of factors which are susceptible to interfere with
      each other and to affect the coronary risk after a long period of exposure. The
      methodology of nutritional studies relies on known and validated enquiry
      techniques, but they are difficult to perform in the general population. The
      lipid nutritional hypothesis of coronary disease was centred on cholesterol and
      the saturated fatty acids. This lipid theory has allowed great advances in the
      pathophysiological and therapeutic areas. The concepts of a French paradox and
      global diet have allowed research in nutritional epidemiology to be refocused on
      other nutrients (lipids and non-lipids) and on alimentary fashions and lifestyle
      in general. The success of proposed diets at the population level depends
      strictly on correctly validated scientific data, and on the cultural and social
      context of where the prevention messages warrant dissemination.

PMID- 14655546
TI  - [Dietary primary prevention of cardiac ischemic diseases].
AB  - Population studies have shown that ischaemic cardiopathy is more frequent in
      countries where the inhabitants have diets rich in saturated fats and in
      cholesterol, and where cholesterolaemia is raised. The epidemiological data from
      large prospective studies have shown that total cholesterolaemia is positively
      correlated with coronary risk. Therapeutic trials performed with the statins in
      particular have demonstrated that a reduction in LDL cholesterol allows a
      reduction in coronary morbidity, suggesting a causal role for cholesterol.
      Primary prevention dietetic trials have often been disappointing, probably due to
      a drop in cholesterol which is too modest, insufficient study size and duration,
      and perhaps also because they concerned low risk subjects. A meta-analysis of 27
      primary and secondary prevention dietetic studies produced evidence of a
      reduction in morbidity, principally when the studies lasting less than 2 years
      were not taken into account. In this meta-analysis the drop in cholesterol was
      correlated with a reduction in clinical events. The benefit of a modified fat
      diet in primary prevention is therefore potentially significant if it is
      maintained for a sufficient length of time. The very positive results of the
      American national programme of nutritional intervention, which has had an
      undeniable impact on the prevalence of lipid disorders in the general population
      and secondarily on coronary mortality, favours the continuation of this mode of
      prevention.

PMID- 14655547
TI  - [Nutritional counseling for coronary and hypertensive patients].
AB  - Nutritional recommendations constitute a major aspect of the long term management
      of coronary and hypertensive patients, for which the established evidence is more
      and more solid. The benefits are not limited solely to the impact on weight and
      lipid parameters. In coronary patients, besides the reduction in saturated fatty
      acids, which is always indicated, an increase in the intake of omega-3 fatty
      acids is associated with a significant reduction in morbidity and mortality,
      notably with sudden death. Intake of folates is also beneficial, as well as fruit
      and vegetable consumption. These elements are constituents of alimentary models
      such as the mediterranean diet. In hypertensives, weight reduction, limitation of
      alcohol and sodium intake, and increasing potassium and magnesium intakes have a
      demonstrable effect. Evaluation of patient compliance to nutritional
      recommendations is just as important as that of compliance to treatments and
      control of classic risk factors.

PMID- 14655548
TI  - [From today's foods to those of the future].
AB  - The prevention of cardiovascular diseases, and more generally of metabolic
      syndrome, goes with a well chosen diet. However, faced with a raft of often
      contradictory information, many patients can become disorientated. The role of
      the practitioner is to supply adapted, personaliZed and scientifically consensual
      advice. The consumption of certain types of foods naturally concentrated in
      protective elements should be favoured, such as those rich in folates, omega 3
      fatty acids, and potassium, and low in sodium chloride. Furthermore, some new
      foodstuffs are appearing which have been subjected to modifications in their
      composition: enriched with certain nutrients or micronutrients, low in sugar and
      certain fats.... Thus, for example, margarines rich in phytosterols appear
      interesting despite limitations in their use; similarly, precautions of usage
      should accompany the consumption of products enriched with omega 3,
      sweeteners.... These attractive appearing and "gustatively correct" foods of the
      future will have more and more pronounced health claims. But alimentary
      innovation, relying on this basis in order to conquer new sections of the market,
      risks causing new nutritional imbalances. The practitioner must therefore remain
      sensible with nutritional advice and take account of economic and regional
      aspects by adapting it for each patient.

PMID- 14655549
TI  - [Pain diagnosis as basis of pain therapy].

PMID- 14655550
TI  - [Rheumatology. What is your diagnosis? Duodenal ulcer].

PMID- 14655551
TI  - [Prophylactic treatment of cluster headache with verapamil].
AB  - Verapamil is the preventive therapy of choice for cluster headache. The
      recommended dose ranges from 240-720 mg/day. In a retrospective study nine
      patients with episodic and three patients with chronic cluster headache were
      analyzed. In episodic cluster headache early treatment onset stopped attacks
      within 20 days in 80%, late treatment onset was successful within ten days in
      67%. Early treatment onset shortens episode duration by four times. The
      recommended dose is 360 mg/day. Chronic cluster headache probably requires higher
      doses.

PMID- 14655552
TI  - [Algorithm for diagnosis and therapy of pain].
AB  - Certain basic principles are applicable to all forms of pain treatment when the
      aims are pain relief and the avoidance of chronicety. Such algorithms, as
      guidelines are even more important when pain is becoming chronic. The use of the
      described algorithms is necessary in the diagnosis and therapy of acute pain and
      also to avoid the establishment of chronic pain due to the changes of
      neuroplasticity in the central nervous system. The most important basic
      principles in the form of algorithms are first of all that therapies should be
      simultaneously applied and not sequentially. Secondly, the challenge should be
      met to create a concept where by various therapies can be preformed in a parallel
      fashion, without compete one another and being effective on different aspects and
      causes of the pain.

PMID- 14655553
TI  - [An interventional pain management. An update].
AB  - Due to the increasing knowledge on neuroplasticity and due to the unsatisfactory
      outcomes from behavioristic treatment alone interventional pain management is
      again becoming interesting. Interventional diagnostic procedures can determine
      the origin of pain in respect to anatomical structures and might differentiate
      the qualities of pain. Thus guidelines can be developed for either conservative
      pharmacological, interventional or cognitive-behavioristic treatment.
      Interventional diagnostic and therapeutic procedures have to be made precisely,
      using imaging techniques with contrast media and have to be well documented.

PMID- 14655554
TI  - [Claudicatio intermittens. Narrow spinal canal].
AB  - Degenerative changes in the vertebrae can lead to narrowing of the spinal canal.
      This is most often the cause of back pain and radiating pain in the legs, which
      in turn can cause problems with mobility. The diagnosis can be verified through
      radiological evidence. When conservative treatment and injections do not improve
      the condition or when there is evidence of paraethesia the best course of
      treatment is operative decompression procedure. Through this procedure results of
      a quick regression of pain and improved mobility are experienced. The operation
      has no risk, a quick recovery period and can be carried out in old patients.

PMID- 14655555
TI  - [Obstetric care--on its way to a new era?].

PMID- 14655556
TI  - [Pregnancy--an immunological challenge].

PMID- 14655557
TI  - [Fetal cells in the pregnant woman's blood as material for fetal diagnosis].

PMID- 14655558
TI  - [Fetal programming of chronic diseases].

PMID- 14655559
TI  - [Fetal therapy].

PMID- 14655560
TI  - [Erythrocyte immunization in pregnancy].

PMID- 14655561
TI  - [Parvovirus B19 infection in pregnancy].

PMID- 14655562
TI  - [Monitoring of intrauterine growth retardation].

PMID- 14655563
TI  - [The National Birth Cohort--Better Health for Mother and Child].

PMID- 14655564
TI  - [Organization of obstetric ultrasound in Denmark 2000. Description of the
      development since 1990].

PMID- 14655565
TI  - [Ultrasonography of pregnant women in Denmark 1999-2000. Description of the
      development since 1980-1990].

PMID- 14655567
TI  - [Twin pregnancies: how should they be monitored and how should they be
      delivered?].

PMID- 14655566
TI  - [Cervical length as a predictor of preterm delivery].

PMID- 14655568
TI  - [Is the increasing frequency of Cesarean sections due to the increasing maternal
      age?].

PMID- 14655569
TI  - [Fathers' role in pregnancy and childbirth].

PMID- 14655571
TI  - [Common value attitude for all adults with mental disease is a utopia].

PMID- 14655572
TI  - [Cornering oneself].

PMID- 14655570
TI  - [Pregnant immigrant women in Scandinavia].

PMID- 14655573
TI  - [Blood donation! Is acupuncture performed by dentists a contraindication?].

PMID- 14655574
TI  - [Medication errors and anticoagulant therapy].

PMID- 14655575
TI  - [Focusing on costs is not enough].

PMID- 14655576
TI  - [Significance of a fair IQ].

PMID- 14655577
TI  - Migration law, the family court and therapeutic jurisprudence.

PMID- 14655578
TI  - Travels of a medical record and the myth of privacy.

PMID- 14655579
TI  - Medication errors: inadvertent administration of potassium chloride.

PMID- 14655580
TI  - Nurses and liability--uncertain times ahead.

PMID- 14655581
TI  - Cattanach v Melchior (2003) 77 ALJR 1312; [2003] HCA 38.

PMID- 14655582
TI  - The structure of medical malpractice decision-making in Japan.
AB  - The article summarises the problems in the medical malpractice litigation systems
      in the United Kingdom and Japan, demonstrating the similarities and identifying
      the length of time between initiating an action and its decision and other
      factors responsible for lengthy litigation. Based on analysis of decisions of
      medical malpractice cases between 1986 and 1998 in Japan, the functioning of the
      Japanese medical malpractice litigation system is discussed. Lengthy litigation
      is shown to be correlated with outcome and implies that the Japanese medical
      dispute resolution mechanism favours those who can endure lengthy litigation,
      namely the defendants, who are physicians or hospitals. In view of the
      similarities between the two systems, it is likely that the same bias--that the
      wealthier party in the litigation is more likely to win the case--also occurs in
      medical malpractice litigation in the United Kingdom and Australia.

PMID- 14655583
TI  - Gynaecological cytopathology and the search for perfection: civil liability and
      regulatory ramifications.
AB  - The article analyses the potential for false negative and false positive results
      from Pap smear testing by gynaecological cytopathology laboratories. It also
      reviews case law in relation to the liability of general practitioners,
      gynaecologists, cytoscreeners and pathologists in respect of cervical cancer
      diagnoses. It argues that the concerns expressed in the 1990s about unfair
      findings of liability against cervical screeners have not been borne out,
      liability only having been found by the courts where culpable failure to adhere
      to the standards to be expected of professional behaviour has been established by
      probative evidence. It argues that the challenge for the future is for cytology
      screening to articulate definitively where the distinctions lie between
      acceptable and unacceptable error and for the medical profession and the legal
      profession to accommodate to the limitations of gynaecological cytopathology.

PMID- 14655584
TI  - The defence of therapeutic privilege in Australia.
AB  - Therapeutic privilege is a defence that excuses a medical practitioner or other
      health professional from complying with the requirements of full disclosure to a
      patient in circumstances where it is reasonably considered that such disclosure
      would be harmful to that patient's health or welfare. Although the concept
      originated in the United States, the defence has been applied in Australia, and
      was specifically endorsed as part of Australian law by the High Court in Rogers v
      Whitaker (1992) 175 CLR 479. However, there has been negligible application of
      the defence since that endorsement. This article examines the doctrine of
      therapeutic privilege in the present Australian medico-legal environment. After
      an examination of the concept and its three constituetent elements, the article
      canvasses the limited instances of judicial approval of the defence prior to
      Rogers v Whitaker. The author then analyses, by reference to reported and
      unreported case law, why the defence has been so narrowly interpreted since, such
      that it has come to occupy an almost untenable position in Australia's medical
      jurisprudence.

PMID- 14655585
TI  - Transferring the burden of risk in private health care: medical indemnity
      insurance reform.
AB  - This article provides an overview and critique of the recent medical indemnity
      insurance reforms implemented by the Commonwealth Government. The first part of
      the article sets out a number of the practical difficulties associated with the
      reforms whilst in the second part an analysis is given of the social philosophies
      and economic approaches that underlie them. The weaknesses and strengths of
      shifting the medical indemnity insurance market from a free-market approach to be
      more in line with the liberal-welfarist approach are considered, as is the need
      for each approach to be supplemented with a more comprehensive understanding of
      the human good.

PMID- 14655586
TI  - Why wrongful birth actions are right.
AB  - A wrongful birth action is a claim in negligence brought by parents of a child
      against a doctor who has "wrongfully" caused their child to be born. These claims
      can be divided into two categories: those where a doctor performs a failed
      sterilisation procedure that leads to a healthy child being born; and those where
      a doctor fails to provide sufficient information to allow parents to choose to
      abort a handicapped child. The recent decision of the High Court of Australia in
      Cattanach v Melchior (2003) 77 ALJR 1312 falls into the former category. The
      decision to allow the parents to receive damages for the costs of raising and
      maintaining their child has generated much public debate. Despite the endorsement
      of this "wrongful birth" action, there are indications that the legislature will
      overturn the decision. This article examines whether there is a sound doctrinal
      basis for recognising wrongful birth actions.

PMID- 14655587
TI  - Importing and exporting gametes and embryos under the Infertility Treatment Act
      1995 (Vic): an unconstitutional restraint on free trade?
AB  - Since the introduction of the Infertility Treatment Act 1995 (Vic), it has been
      illegal to import into or export from Victoria a gamete or embryo outside the
      human body without the approval of the Infertility Treatment Authority. But is s
      56 unconstitutional and therefore invalid by reason of contravening the freedom
      of interstate trade guarantee by s 92 of the Commonwealth Constitution? By
      exploring the nature and effect of s 56 this article demonstrates that s 56 may
      impose a "discriminatory" and "protectionist" burden that renders s 56 invalid.

PMID- 14655588
TI  - [Complications of transsphenoidal pituitary surgery].

PMID- 14655589
TI  - [Diaphragm pacing with a spinal cord stimulator].
AB  - BACKGROUND: Diaphragm pacing with electrical stimulation of the phrenic nerve is
      an established treatment for central hypoventilation syndrome. The device,
      however, is not readily available in Japan. For pain control, we applied the
      spinal cord stimulator to bring about phrenic nerve stimulation. The purpose of
      this study is to evaluate the efficacy and feasibility of phrenic pacing using
      the compromise method. METHOD AND PATIENTS: We implanted a spinal cord stimulator
      in five patients with chronic central hypoventilation. The stimulation electrode
      was placed along the phrenic nerve in the neck, and the device was implanted in
      the anterior chest. We used the cyclic mode, and set the parameters at 1 second
      ramp up, 2 second on, 3 second off. The pulse width and the frequency were set at
      150 mu sec and 21 Hz respectively. The amplitude was adjusted to obtain
      sufficient tidal volume and to maintain PaCO2 at around 40 mmHg. RESULT: During
      the follow-up period from 3 to 34 months (mean 23), stable and sufficient
      ventilation was observed in all patients without complications. CONCLUSION:
      Though longer follow-up is necessary, diaphragm pacing with the spinal cord
      stimulator is feasible as a treatment for central hypoventilation syndrome.

PMID- 14655590
TI  - [Papillary glioneuronal tumor with highly degenerative pseudopapillary structure
      accompanied by specific abortive glial cells: a case report].
AB  - Recently, unusual examples of tumors of the mixed glioneuronal type have been
      reported, including the papillary glioneuronal tumor (PGNT). A 23-year-old woman
      with a 2-3 months history of headache and insomnia presented with a tumor.
      Neuroimaging showed a right temporal lobe cystic tumor with a mural nodule
      enhanced by contrast medium. She underwent gross total resection of the tumor.
      The tumor was histologically marked by a mixture of glial and neural components.
      A pseudopapillary component was comprised of highly hyalinized vessels surrounded
      by a single layer of thin spindle cells stained for glial fibrillary acidic
      protein. Specific abortive glial cells stained for vimentin/S-100 protein
      accompanied pseudopapillary structure. Intervening neural areas were occupied by
      neural cells of varying size, including neurocyte-like cell and ganglionic cells.
      Ganglionic cells demonstrated abnormal cluster, lack of normal polarity and
      epiperikaryal immunoreactivity for synaptophysin staining suggesting neural
      neoplastic nature. No mitotic activity or necrosis was noted. A MIB-1 labeling
      index was 1.8%. Our patient remains free of disease 33 months after surgical
      treatment.

PMID- 14655591
TI  - [Granulomatous change of the pituitary stalk caused by Rathke's cleft cyst: a
      case report].
AB  - We report a case of granulomatous change of the pituitary stalk caused by
      Rathke's cleft cyst. A 50-year-old woman complained of thirst and polyuria in
      December 2000. In January 2001, the patient was suspected to have diabetes
      inspidus, and MR Imaging showed a suprasellar mass of the pituitary stalk. The
      mass was totally resected by the trans-sylvian approach. Pathological diagnosis
      was Rathke's cleft cyst with subsequent granulomatous change. To our knowledge,
      there have been 11 cases of Rathke's cleft cyst and subsequent granulomatous
      change. In the literature, diabetes inspidus was not improved by surgical
      procedures. However, we suggest that the mass should be totally resected, because
      some cases in literature showed visual disturbance or hypo-pituitarism under
      observation.

PMID- 14655592
TI  - [Rosai-Dorfman disease presenting with multiple intracranial and intraspinal
      masses: a case report].
AB  - Rosai-Dorfman disease (RDD), a systemic histioproliferative disorder, was first
      described by Rosai and Dorfman in 1969. However, only 41 cases involving the
      central nervous system have been reported. The authors present a rare case of RDD
      with multiple intracranial and spinal lesions mimicking multiple meningioma. A 59
      year-old woman was admitted to our hospital with a history of bilateral visual
      impairment. MRI demonstrated multiple central nervous system lesions in the
      suprasellar region, right temporal convexity, left frontal convexity, left
      cerebello-pontine angle and C5 level of the spinal cord. Preoperative neuro
      imaging studies suggested multiple meningioma. Subtotal removal of the
      suprasellar lesion was performed, followed by gamma knife radiosurgery to the
      residual lesion and the other intracranial lesions. All intracranial lesions
      disappeared following gamma knife radiotherapy. The spinal lesion, however, was
      completely excised one year after the initial operation following the appearance
      of sensory disturbance. Both intracranial and spinal lesions were diagnosed as
      RDD on histological examination. No recurrences have been detected on MRI two
      years after the initial operation. Seeing the good results already achieved by
      surgical removal of RDD, this case suggests that the combination of surgery and
      gamma knife radiotherapy might improve further.

PMID- 14655593
TI  - [Neuroendoscopic treatment for Rathke's cleft cyst: transventricular approach to
      suprasellar cystic lesion].
AB  - We report a case of a Rathke's cleft cyst, which was successfully treated by
      neuroendoscopy. The endoscopic procedure for the intra-suprasellar cystic lesion
      used the transventricular approach, similar to that of third ventriculostomy. A
      66-year-old woman suffered from headache, nausea and constriction of the visual
      field. Magnetic resonance imaging (MRI) on admission showed an intra-suprasellar
      cystic lesion. Biopsy of the cyst wall and fenestration of the floor of the third
      ventricle was performed using an endoscopic transventricular approach. The cyst
      content was totally aspirated, using a suction system which was connected to the
      operation channel of the endoscope. The histological diagnosis was Rathke's cleft
      cyst. No post-operative complication was observed. The endoscopic
      transventricular approach is safe and most suitable in terms of minimum
      invasiveness for the intrasuprasellar cystic lesion. We consider that
      neuroendoscopic transventricular approach will become the common surgical method
      of choice for treating a suprasellar cystic mass lesion.

PMID- 14655594
TI  - [Atypical presentation of a dermoid cyst with porencephaly].
AB  - We report a case of a dermoid cyst in the parasellar area associated with
      porencephaly. A 22-year-old man presented with headache and visual disturbance.
      Non-enhanced brain CT showed a high density mass in the parasellar area and a low
      density area in the left temporal lobe. On gadolinium-enhanced T1-weighted
      images, a partial rim enhancement was present in the parasellar region. A
      presumptive diagnosis of Rathke cleft cyst, craniopharyngioma, non-function
      pituitary adenoma, or germ cell tumor was considered. A left frontotemporal
      craniotomy was performed and the tumor was removed almost totally. The tumor was
      well-capsulated and contained whitish, milky debris. The histologic diagnosis was
      dermoid cyst. The temporal lobe lesion was porencephaly. The postoperative course
      was uneventful. Their most typical aspect is the presence of a low-density mass
      on CT, allowing an easy radiologic diagnosis of dermoid cyst containing lipids.
      Enhancement following contrast administration is uncommon. The hyperdensity may
      be related to the high protein content of the lesion. The hyperdense aspect of
      the lesion on CT, and the presence of rim enhancement made the radiologic
      diagnosis of a dermoid cyst difficult in this case. A case of dermoid cyst
      associated with porencephaly has not yet been reported in the literature.

PMID- 14655595
TI  - [Multiple intracerebral microhemorrhages associated with primary aldosteronism: a
      case report].
AB  - We have observed dot-like low intensity spots (a dot-like hemosiderin spot:
      dotHS) on T2*-weighted (T2*-w) MRI, subsequently diagnosed histologically as
      previous microbleeds associated with lipohyalinosis, amyloid angiopathy and
      cerebral small vessel disease (SVD) including an intracerebral hematoma (ICH) and
      a lacunar infarction. According to the literature, primary aldosteronism (PA),
      characterized by hypertension, is related to SVD. A 49-year-old female with a
      long history of untreated hypertension secondary to PA was admitted to our
      hospital for medical examinations on July 18th, 2000. She had the stepwise
      development of dementia, dysarthria and gait disturbance (right hemiparesis). CT
      and MRI demonstrated multiple lacunar infarctions. She was readmitted to our
      hospital on Jan 23rd, 2002. A neurological examination revealed right
      hemiparesis, dysarthria and consciousness disturbance. CT on admission
      demonstrated ICH in the left midbrain. Six days after the hemorrhage, T2*-w MRI
      showed thirty-two dotHSs in the basal ganglias and the cortical-subcortical
      regions. The incidence of ICH in patients with hypertension secondary to PA is
      reported to be higher than in patients with essential hypertension. Multiple
      dotHS may be associated with ICH, lacunar infarction, and severe microangiopathy
      related to hypertension secondary to PA.

PMID- 14655596
TI  - [Two cases of lymphocytic infundibuloneurohypophysitis].
AB  - We report two cases of lymphocytic infundibuloneurohypophysitis (LIH). A 32-year
      old male and a 13-year-old male were admitted to our hospital because of a sudden
      occurrence of the diabetes insipidus (DI). MRI of both patients showed the
      disappearance of hyperintensity of the posterior pituitary in T1WI, pituitary
      stalk swelling and enlargement of the pituitary gland, with homogeneous
      enhancement by gadolinium. We thereby diagnosed LIH, so neither patient was
      operated on, but both were followed-up conservatively. We reviewed 51 cases of
      LIH. The patient's ages ranged from 4 to 74 years (mean 45.4 years). Based on the
      initial symptoms, DI was found in all cases. Almost all these cases revealed
      characteristic MRI findings similar to those in our cases. The mean follow-up
      period was 3.1 years. The rate of disappearance of radiological abnormalities was
      56.2%, but only 13.7% of DI improved. If we encounter a patient presenting with
      idiopathic DI whose MRI is strongly suggestive of LIH, and barring the necessity
      of an urgent operation, careful conservative treatment is advised.

PMID- 14655597
TI  - [Interictal discharges of epilepsy: basic knowledge of clinical nerve physiology
      for neurosurgeons].

PMID- 14655598
TI  - [Testicular microlithiasis: report of 14 cases].
AB  - Testicular microlithiasis (TM) is a comparatively rare condition in which
      calcified congelations fill the lumina of the seminiferous tubules. Using high
      frequency linear transducers (10 MHz), TM is easily demonstrated as tiny punctate
      echogenic foci, which typically do not give an acoustic shadow, and is classified
      into classic type (CTM) and limited type (LTM) on the basis of the presence of
      five or more microliths at least on one image of the testes. Fourteen patients
      were found to have TM, 6 of which were LTM and 8 were CTM. In one patient with
      CTM, coexisting mixed germ cell tumor (seminoma, embryonal cell carcinoma) was
      demonstrated. Until further data are available, it seems reasonable to consider
      patients with TM as having an increased risk of developing a primary testicular
      tumor.

PMID- 14655599
TI  - [Stage A prostate cancer: comparison of subclassification between Japanese rule
      and TNM, and outcome].
AB  - Between 1980 and June, 2002, transurethral resection of prostate was performed
      against 3294 cases of benign prostatic hyperplasia, and 144 cases of stage A
      cancer were detected (4.4%). Among these cases, 136 cases which had complete
      records of examination were studied. Annual number of stage A and A1:A2 ratio
      were not influenced by introducing PSA determination from 1991, although the
      number of T1c has been increasing gradually. Since subclassification of stage A
      is different between Japanese rules (A1; 3 chips of cancer with well
      differentiated adenocarcinoma, A2; others) and TNM (T1a; 5% of less number of
      chips with cancer, T1b; others), two criteria were compared. Coincidence was
      found with 93.7%, and disagreement was due to ratio of number of chips with
      cancer to whole number resected, or different grade. The former difference was
      caused by a larger or smaller prostate. Most cases of A1 and A2 were subjected to
      watchful waiting or subsequent therapy. PSA was elevated in 10 cases (7%), two of
      which died from progression of cancer. Other cases were disease-free. Individual
      pathological findings are important for subclassification of stage A.

PMID- 14655600
TI  - [Malignant pheochromocytoma responsive to multimodal therapy: a case report].
AB  - A 62-year-old man underwent right adrenalectomy for pheochromocytoma in May 1987.
      He was referred to our department for a right renal tumor suggested by ultrasound
      sonography in December 2000. Computated tomography and MRI showed a 10 cm mass
      arising from the upper pole of the right kidney. 131I-MIBG scintigram showed
      strong radio isotope accumulation consistent with the tumor. Right nephrectomy
      and subsegmental hepatectomy were performed. Histological findings led to the
      diagnosis of malignant pheochromocytoma. In February 2001, he complained of
      paraplasia due to Th2 bone metastasis. Radiation and CVD (cyclophosphamide,
      vincristine, dacarbazine) chemotherapy resulted in tumor regression and marked
      improvement of clinical symptoms.

PMID- 14655601
TI  - [Inflammatory pseudotumor of the urinary bladder diagnosed using 3D-CT
      cystoscopy].
AB  - Inflammatory pseudotumor of the urinary bladder is a rare benign entity of the
      submucosal stroma that can easily be mistaken for a malignant neoplasm both
      clinically and histologically. We report a case of an inflammatory pseudotumor of
      the urinary bladder in which 3D-CT cystoscopy aided in the diagnosis. A 38-year
      old man presented with persistent miction pain, penile pain, and dysuria despite
      symptomatic treatment at another hospital. Cystoscopic examination, MRI and 3D-CT
      cystoscopy revealed a 3.0 X 3.0 cm wide-based nonpapillary tumor located at the
      anterior dome of the urinary bladder. Transabdominal biopsy and transurethral
      resection were performed and the tumor was suspected to be transitional cell
      carcinoma. A partial cystectomy and urachus excision were then performed for
      suspected urachal tumor based upon the radiological examinations. Careful
      examination of the specimen revealed an inflammatory pseudotumor. We discuss 20
      cases of inflammatory pseudotumor of the urinary bladder including ours.

PMID- 14655602
TI  - [A case report: mucinous carcinoma of prostate].
AB  - We present a case of mucinous carcinoma of prostate. A 64-year-old man visited
      our hospital because of high score of prostate specific antigen (PSA). Prostatic
      biopsies were performed twice, but cancer was not found. Since the PSA value
      elevated gradually and a hard nodule in the right lobe of prostate became
      palpable, we repeated the biopsy that revealed cancer. Retropubic radical
      prostatectomy was performed and pathological examination revealed mucinous
      carcinoma of prostate. Mucinous carcinoma of prostate is rare, and to our
      knowledge, only 46 cases have been reported in the Japanese literature.

PMID- 14655603
TI  - [Periureteral inflammatory pseudotumor: a case report].
AB  - A 59-year old female presented with right flank pain and hydronephrosis.
      Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) before
      admission (August 2001), revealed a periureteral mass measuring 11 cm in length
      along the right ureter. Since the preoperative image examinations could not
      exclude a malignancy, she was admitted for surgery. After admission, however, she
      presented no abnormal findings in laboratory investigations including tumor
      markers, urinalysis, urine cytology and retrograde pyelography. C-reactive
      protein was normalized. CT after admission (September 2001), showed spontaneous
      regression of the mass. We cancelled the operation and decided to carefully watch
      this lesion by CT. The lesion continued to regress thereafter. Judging from the
      clinical course, we regard the mass as inflammatory pseudotumor although
      pathological diagnosis was not performed. The possibility of preserving the
      urinary tract in this disease is discussed by reviewing the previously reported
      inflammatory pseudotumor of the upper urinary tract.

PMID- 14655604
TI  - [Reiter syndrome after intravesical Bacillus Calmette-Guerin (BCG) immunotherapy:
      a case report].
AB  - A 56-year-old man who had previously undergone transurethral resection and intra
      arterial chemotherapy for bladder cancer developed irritable bladder, bilateral
      conjunctivitis and arthritis including the knees, ankles and sacroiliac joints
      after starting intravesical Calmette-Guerin bacillus (BCG) immunotherapy. These
      symptoms were in agreement with the features of Reiter syndrome. One month after
      cessation of the intravesical BCG immunotherapy and initiation of the treatment
      with a non-steroidal anti-inflammatory drug (NSAID), he was not complaining of
      symptoms. Reiter syndrome is an uncommon complication after intravesical BCG
      immunotherapy. Nevertheless, since the prolonged arthritis has a possibility to
      cause joint deformity, we must pay serious attention to this side effect.

PMID- 14655605
TI  - [Traumatic dislocation of the testis: report of five cases].
AB  - Five cases of traumatic dislocation of the testis are described. Dislocation of
      the testis is a rare injury, with only 93 cases having been reported in Japan.
      Recent reports have revealed an increased number of motor cycle accidents
      involving teenage patients. Early surgical management is required, since closed
      reduction is difficult. We discuss its classification, diagnosis and treatment.

PMID- 14655606
TI  - [A case of non-functioning adrenocortical adenoma associated with renal cell
      carcinoma].
AB  - Left renal and left adrenal masses were incidentally found by computerized
      tomography (CT) in a 56-year-old man who was admitted to our hospital for
      treatment of upper digestive tract hemorrhage. Apparently no clinical signs
      suggestive of Cushing's syndrome existed. The renal tumor was diagnosed as renal
      cell carcinoma based on the findings on enhanced CT. 131I-adosterol uptake in the
      examination of adrenal scintigraphy under dexamethasone suppression was
      definitely increased in the left adrenal gland, although hormonal examinations of
      serum and urine for adrenal functions were within the normal range. Plasma
      adrenocorticotropic hormone (ACTH) and serum cortisol were suppressed by
      administration of 2 mg dexamethasone for 2 days. The left kidney was radically
      removed by surgery together with the left adrenal gland. Histological diagnoses
      were left renal cell carcinoma and adrenocortical adenoma.

PMID- 14655607
TI  - [Retroperitoneal angiomyolipoma with rapidly progressing intracystic hemorrhage
      and lymph node involvement: a case report].
AB  - We report a very rare case of retroperitoneal angiomyolipoma with rapidly
      progressing intracytic hemorrhage and lymph node involvement in a 34-year-old
      female. She was admitted to our hospital complaining of a severe pain in the
      lower abdominal region, followed by oligemic shock. Abdominal enhanced computed
      tomography (CT) demonstrated a retroperitoneal giant cyst with intracystic
      hematoma, which displaced the left kidney anteriorly. Because transarterial
      embolization was unsuccessful transabdominal left nephrectomy combined with
      excision of the giant cyst was performed to keep the continuing hemorrhage under
      control. Simultaneously, a swollen paraaortic lymph node was also resected. The
      histologic findings of resected tissue and lymph node were retroperitoneal
      angiomyolipoma with lymph node involvement. The patient is being followed up at
      our hospital without recurrence.

PMID- 14655608
TI  - [A case of ammonium urate urolithiasis with Crohn's disease].
AB  - A 28-year-old woman suffering from Crohn's disease since 15 years of age
      presented with left back pain. She had undergone a colectomy when she was 20
      years old and an ileostomy when she was 25 years old. She had been treated with
      mesalazine and pernasal nutrition (Elental) Ultrasonography showed left side
      hydronephrosis and a renal stone in the left renal pelvis. Computed x-ray
      tomography revealed a stone measuring 1.5 x 1.0 cm2 at the ureteropelvic
      junction, which was radiolucent on an abdominal radiograph. The renal stone was
      successfully treated with 10 exposures of extracorporeal shockwave lithotripsy.
      Ninety eight percent of the passed stone was composed of ammonium urate. Crohn's
      disease-related poor nutrition and dehydration are presumed to have been possible
      induction factors in the forming of the ammonium urate stone in this case.

PMID- 14655609
TI  - [Transitional cell carcinoma of the ureter with inverted proliferation: a
      difficult case to make a differential diagnosis with ureteral polyp].
AB  - A 59-year-old man was admitted to our hospital in June 2001 for evaluation of an
      asymptomatic microscopic hematuria. One year prior to presentation, he had a
      spontaneous discharge of a left ureteral stone. Excretory urography and
      retrograde pyelography showed a filling defect in the middle portion of the left
      ureter. Cystoscopic examination did not reveal any abnormality, and urinary
      cytology was class I. Cold cup biopsy was performed under ureteroscopy, and
      pathology revealed inflammatory fibrovascular tissue but with no malignancy.
      Selective washing cytology was class III, whereas selective washing cytology done
      at the referring hospital was reported to be class V. Under a preoperative
      diagnosis of a left fibroepithelial ureteral polyp or a transitional cell
      carcinoma, left segmental ureterectomy was performed. The tumor was 5 x 5 x 5 mm
      in size, pedunculated, and smooth-surfaced. Intraoperative pathological
      examination of a frozen section showed an inverted type transitional cell
      carcinoma. Therefore, a left nephroureterectomy was performed, and the final
      histopathological examination confirmed an inverted type transitional cell
      carcinoma of grade 2. The patient is healthy and free of disease 15 months after
      operation. We also reviewed the current literature relating to transitional cell
      carcinomas of the ureter with inverted proliferation.

PMID- 14655610
TI  - [A case of carcinosarcoma of the urinary bladder].
AB  - We report a case of carcinosarcoma of the urinary bladder. A 50-year-old man
      visited our hospital with asymptomatic macroscopic hematuria as a chief
      complaint. Excretory urography revealed a filling defect in the right wall of the
      bladder, and subsequent cystoscopy revealed a non-papillary tumor above the right
      orifice. The patient underwent total cystectomy and had a neobladder constructed
      with the ileum (Hautmann's method). Microscopic examination showed a tumor
      composed of a mixture of transitional cell carcinoma and rhabdomyosarcoma.
      Immunohistochemical examination showed that the area of epithelium component was
      positive for cytokeratin and the non-epithelium area was positive for vimentin,
      there being no relationship between the two. The patient began complaining of
      coccyalgia 10 days after the operation. He died about 1 month after the operation
      because of the recurrence in the pelvic cavities.

PMID- 14655611
TI  - [A case of clear cell adenocarcinoma of the female urethra].
AB  - Clear cell adenocarcinoma of the female urethra is extremely rare. We herein
      describe the 33rd case of clear cell adenocarcinoma of the female urethra in
      Japan. A 54-year-old female who presented with pollakisuria was referred to our
      department. Transvaginal examination showed a walnut-sized firm mass on the
      anterior vaginal wall. Computed tomography, magnetic resonance imaging (MRI),
      cystourethroscopy and the histopathological findings of the biopsied specimen
      revealed adenocarcinoma of the urethra. Anterior pelvic exenteration and ileal
      conduit urinary diversion were performed and the final pathological diagnosis was
      clear cell adenocarcinoma of the urethra, pT3, pN2. No further adjuvant therapy
      was conducted. She remains alive 6 months after surgery in spite of paraaortic
      and inguinal lymph node metastases.

PMID- 14655612
TI  - [Clinical statistics of the operations during a 10-year period at the Department
      of Urology, Kouga Public Hospital: 1993-2002].
AB  - A clinical statistical survey of the operations was performed at our urology
      department during a 10-year period from 1993 to 2002. The total number of
      operations was 2,909 including 806 sessions of extracorporeal shock-wave
      lithotripsy (ESWL) that started in 1999. Since a combination unit of ESWL,
      fluoroscopic apparatus and digital video-urodynamics system was built next to the
      outpatient department in 1999, the number of operations and examinations has
      dramatically increased. Operations for bladders made up the greatest portion of
      all the surgeries and especially transurethral resection of bladder tumor and
      hydrodistention have been increasing.

PMID- 14655613
TI  - It's not business as usual: you can fight patient surges with an aggressive plan.
AB  - Surges in patient volume are inevitable but, nevertheless, merit an aggressive
      response. A well-designed plan can clear your waiting room quickly and ensure
      high-quality care despite high volume. Make sure your ED is adequately staffed
      for known high-volume periods. Use physician triage when patients back up in the
      waiting area. Utilize on-call physicians and nurses when necessary, even though
      that decision can be difficult.

PMID- 14655614
TI  - Kid-friendly waiting areas in ED boost satisfaction.

PMID- 14655615
TI  - Heart care methods put ED in top 5%, can help others.

PMID- 14655616
TI  - Research shows ED case management saves dollars.

PMID- 14655618
TI  - 2003 salary survey results. While economic picture still lukewarm, there are some
      improvements for nurses, good job security.

PMID- 14655619
TI  - ED accreditation update. Disclosure concerns and fears of potential litigation
      prompt options to midcycle self-assessment reporting.

PMID- 14655620
TI  - ED accreditation update. Spell it out: avoid easily misread abbreviations.

PMID- 14655621
TI  - Molecular typing of pathogens.
AB  - Molecular typing and fingerprinting of bacterial pathogens has become a major
      part of epidemiology, disease monitoring, intervention and food safety research.
      This treatise will briefly address the aims of molecular typing and the criteria
      that are important to choose the optimal method of typing. However, since the
      method of choice will depend on a number of factors, including available
      facilities and research goals, no particular methods are recommended; instead,
      theoretical considerations are presented as a guide line for the best decision.
      Since molecular typing is examining the nature of the population genetics of a
      particular organism, it is important to understand how the degree of clonality of
      that particular organism will influence outcome and interpretation of results.
      The mechanisms that lead to non-clonality are briefly outlined. The problems with
      typing of clonal, non-clonal, and weakly clonal populations are briefly treated.
      The merits and myths of multilocus sequence typing (MLST) are discussed.

PMID- 14655622
TI  - [Use of AFLP analysis for the molecular biological fine typing of Campylobacter
      jejuni strains from turkey flocks].
AB  - One of the most promising genotyping methods for microorganisms is the AFLP
      (amplified fragment length polymorphism)-analysis, originally developed to
      genotype plants. The AFLP method has a high discriminatory power and an excellent
      reproducibility. Thus it is suitable for solving taxonomic and epidemiological
      questions. AFLP analysis was used to reveal the genetic diversity of
      Campylobacter (C.) jejuni strains from turkeys. The aim was to detect and
      genotype C. jejuni strains on individual turkeys throughout the complete
      slaughter process. A broad spectrum of genotypes was detectable on the turkey
      skin at the beginning of the slaughter line. At the end of the slaughter process
      after chilling, only a diminished spectrum of genotypes was detectable by AFLP
      analysis, suggesting, that slaughter specific environmental stressors may exert a
      selective pressure on the strain diversity. Our results proved, that AFLP
      analysis is an excellent tool for subtyping large numbers of Campylobacter
      strains.

PMID- 14655623
TI  - [Molecular characterization of Listeria monocytogenes and the significance for
      food hygiene].
AB  - Research on the pathogen Listeria monocytogenes is a key issue both for the
      clinical and the food microbiologist owing to the unique pathway of infection and
      the exposure of humans via contaminated foods. Although, in Austria, the
      incidence of listeriosis is about 870-fold lower than the incidence for
      Salmonella infection, the food law manages both foodborne pathogens with a
      comparable stringency. The current risk management is based on the assumption
      that environmental L. monocytogenes isolates, from which the pool of "foodborne"
      isolates is recruited, are of similar pathogenicity compared to clinical and
      outbreak isolates. This verdict became doubted in the recent years.
      Characterization of L. monocytogenes by virulence gene sequencing, virulence
      studies in vivo and in vitro and by molecular typing was considerably stimulating
      the discussion on virulence variability in L. monocytogenes. This article
      provides insights in the value of epidemiological follow-up studies by presenting
      a typing study on 15 cases of listeriosis observed in a district hospital in
      Turkey. Furthermore results from typing L. monocytogenes either by virulence gene
      sequencing, mismatch amplification mutation assay or by pulsed field gel
      electrophoresis are discussed. The close interaction of molecular microbiology
      with food microbiology both in applied and basic science is currently creating a
      new discipline of molecular food microbiology. We are convinced that veterinary
      medicine will contribute to this exiting development in a fruitful way.

PMID- 14655625
TI  - [Genetic fingerprinting (PFGE) of bacterial isolates for their molecular
      epidemiology].
AB  - The determination of fragment patterns of bacterial genomic DNA after digestion
      with long-range-cutting restriction enzymes and their separation in pulsed-field
      gelelectrophoresis is currently regarded as reliable fingerprinting tool for
      surveillance and identification of infectious sources and routes of bacterial
      pathogens. The PFGE based molecular fingerprinting has been applied and used for
      a broad range of bacterial species. As a prerequisite for its application in
      national and international network studies (German PulseNet, PulseNet USA,
      Salmgene) a common protocol for rapid production (1-2 days) of standardised and
      electronically readable fragment patterns has been developed. National and
      international outbreaks, diffuse outbreaks and long term surveillance of the ups
      and downs of pathogens have been successfully carried out by means of PFGE
      studies. The international outbreak of Salmonella enterica serovar Oranienburg
      (2001) due to contaminated chocolate is described here underlining the usefulness
      of PFGE as genetic fingerprinting for epidemiological purposes.

PMID- 14655624
TI  - [Molecular biological detection of tissues of central nervous system in meat
      products].
AB  - In principle, molecular biological methods can be used for the detection of
      specified risk material (SRM) in meat products. We were able to identify suitable
      target mRNAs for the marker proteins glial fibrillary acidic protein (GFAP) and
      myelin basic protein (MBP) of tissues of the central nervous system (CNS). The
      selected primers for GFAP ("GFAP87") and MBP ("MBP51") facilitated the detection
      of CNS in non-heated and heated standards of emulsion type (and raw) sausages
      with defined addition of brain by reverse transcription and polymerase chain
      reaction (RT-PCR). Stability of the mRNA proved to be given over a minimum of 48
      hours. First results indicate an even higher stability of the target mRNAs over
      time and an ample stability against meat technological influences such as
      storage, temperature, and ripening. RT-PCR with GFAP87 facilitates the detection
      of CNS of all relevant slaughter animals in meat products. Thus it can be applied
      in food labeling control. Using RT-PCR and MBP51 as primer we were able to detect
      selectively the CNS of bovines, ovines and caprines but not CNS of porcines and
      poultry. Thus we have a second RT-PCR detection procedure for CNS in meat
      products which, however, yields results equivalent to the legal definition of
      SRM. The further development of these molecular biological methods would be of
      considerable importance for routine food control and reduction of human TSE
      exposure risk.

PMID- 14655626
TI  - [Typing of Salmonella by DNA-microarrays].
AB  - Microarrays (DNA-Chips) are miniaturized carriers on which many nucleic acid
      molecule probes such as oligonucleotides or PCR products are immobilized in a
      high density, and compactness. Homologue DNA hybridises with the immobilized
      complementary nucleic acid probes. This study gives after a short general
      introduction in the principle of DNA-microarrays an overview about published data
      on the field of typing of Salmonella by microarrays. An onset of a DNA-microarray
      developed by the National Reference Laboratory for Salmonella (NRL-Salm) will be
      introduced. By this new technique, it is possible to answer epidemiological
      questions as well as to find genes involved in certain biochemical processes,
      such as pathogenicity or resistance of salmonellae.

PMID- 14655627
TI  - [Suitability of SSCP-PCR analysis for molecular detection of quinolone resistance
      in Campylobacter jejuni].
AB  - Foodborne infections with Campylobacter spp. are increasing, especially
      antibiotic resistant strains are emerging. Quinolone resistant isolates can cause
      failure of therapy in severe clinical infections. Molecular characterisation is
      needed for the detection of resistant variants of C. jejuni. Therefore 23
      isolates from poultry and human medicine as well as three control strains were
      tested for their minimal inhibitory concentration, their Single-Strand
      Conformation-Polymorphism (SSCP)-PCR pattern (a method for the detection of
      resistance determining point mutations), and their sequence of the quinolone
      resistance determining region (QRDR). Six different SSCP types could be
      identified: two types for quinolone resistant isolates and other types containing
      so called silent mutations without influence on the resistance. A genotypic
      monitoring of the quinolone resistance in C. jejuni can be useful for the early
      detection of new resistance variants. As a screening method for detection of
      point mutations in the QRDR the SSCP-PCR can be applied. Compared to other
      genotypic methods the SSCP-PCR is less time and cost consuming and needs only
      standard technical equipment.

PMID- 14655628
TI  - [Molecular biological method cascade for detection, specific isolation and
      characterization of shiga toxin-producing Escherichia coli (STEC) in food].
AB  - Shigatoxin-producing E. coli (STEC) and their subgroup, the enterohaemorrhagic E.
      coli (EHEC) are known since about 25 years. Only EHEC can cause diseases in
      humans. A molecularbiological method cascade is described in this article. It
      contains the following steps: preenrichment, enrichment, preparation of samples
      (DNA extraction), screening PCR, specific STEC isolation by using DNA DNA
      hybridization, verification of isolates as STEC by using PCR, characterization of
      STEC isolates. Pulsed field gel electrophoresis and DNA sequencing are additional
      methods for the detection of clonal correlations. They should be performed in
      special labs, only. Furthermore, some information about an interlaboratory ring
      trial within Germany and some conclusions are given.

PMID- 14655629
TI  - [Food-borne human pathogenic viruses and their molecular detection with special
      consideration of noroviruses and hepatitis A virus in mussels].
AB  - Viruses are increasingly important as etiological agents of gastrointestinal
      infections. Because of improved diagnostic methods, in particular, because of
      molecular biological techniques, viruses can be detected much more frequently as
      pathogens of foodborne diseases. Apart from the hepatitis A virus (HAV) the
      Norovirus (NLV) is becoming more significant. On an international level methods
      are developed to detect the amount of viruses which minimise PCR inhibitors and
      which are applicable in routine diagnostic. There are numerous routines available
      in the field of virus diagnostic in shellfish and oysters which are, however, not
      yet standardised and applicable in the whole of Europe. This review highlights
      viral agents their characteristics as well as food contaminated with viruses.
      While most of the detection methods are cited from the literature, own
      preliminary results of virus detection in mussels are discussed in addition.

PMID- 14655630
TI  - [Multiplex PCR in the framework of an enterococci monitoring project].
AB  - A multiplex-PCR (MPCR) assay was optimised in the framework of an enterococci
      monitoring project in order to accelerate the previous time-consuming biochemical
      testing of enterococcal strains isolated from animal materials and food. The MPCR
      was optimised by variation of annealing temperature, MgCl2-concentration but more
      over by primer combinations and primer concentrations. Reference strains were
      used during the optimization. Afterwards 522 enterococcal field strains were
      examined by the MPCR. Ambiguous results occurred for 20 strains (17 with false
      positive and 3 with false-negative results) which could be explained by the minor
      specificity ("EM"-primers) and sensitivity (ddlE.faecium-primers) respectively.
      Differences also existed between the genus-specific primers "E" and "Ent". The
      first mentioned primers showed weaknesses for the identification of enterococci
      whereas the use of the "Ent" primers inhibited other primers in the MPCR.
      However, the majority of the examined strains could be detected unambiguously, so
      that a differentiation of enterococcal isolates can be recommended by MPCR in
      contrast to the high time-, material- and work-consumption of conventional
      biochemical testings.

PMID- 14655631
TI  - [Use of molecular methods in food microbiology with the example of probiotic use
      of lactobacilli].
AB  - The aim of molecular methods in food microbiology is the identification or strain
      specific differentiation of microorganisms. Identification methods include
      besides taxonomic purposes also the detection of virulence genes or resistance
      markers. Strain specific differentiation is used for epidemiological
      investigations or the quality control of technologically used bacteria. Probiotic
      strains of the Lactobacillus acidophilus-group were investigated with different
      molecular methods: for identification proteinfingerprinting and RAPD-PCR (Random
      Amplified Polymorphic DNA-PCR) were applied, for strain specific differentiation
      pulsed field gel electrophoresis (PFGE) and again RAPD-PCR were used. The
      molecular methods applied should be chosen depending on the objective
      (identification, differentiation) and with respect to the organism to be tested.
      In case of probiotic lactic acid bacteria like the L. acidophilus-group
      proteinfingerprinting has proved to be successful for identification and with
      some limitation also RAPD-PCR. For differentiation PFGE is suitable as well as
      RAPD-PCR. Those methods differ substantially in their work load and in personal
      requirements, and show different power of discrimination and reproducibility
      within and between laboratories. This should be considered while choosing the
      appropriate method.

PMID- 14655632
TI  - [Species and strain specific identification of lactic acid bacteria in complex
      microflora].
AB  - The identification of lactic acid bacteria in a complex microbiota using
      bacteriological culture in combination with phenotypic and genotypic
      identification techniques is laborious and time-consuming. New molecular methods
      permit a fast and culture-independent characterisation of such microbiota.
      Denaturing gradient gel electrophoresis (DGGE) of PCR fragments of the 16S rRNA
      gene has been proven to be a suitable tool. Here the use of PCR-DGGE with group
      specific primers is described to investigate the dynamic of sourdough microbiota
      from addition of the starter until the microbiota remained stable. Species were
      identified by applying an identification ladder obtained from reference strains
      or by sequence analysis of the PCR fragments. Furthermore, a method for detection
      of strains in complex microbiota is described. A strain specific chromosomal DNA
      fragment of Lactobacillus paracasei LTH 2579 was isolated applying the
      subtraction hybridisation. Based on the acquired target sequence a specific PCR
      system was established and combined with a PCR system specific for the species L.
      paracasei. Use of this detection system permitted to identify and quantitatively
      detect L. paracasei LTH 2579 in fermented sausages and upon consumption in faecal
      samples.

PMID- 14655633
TI  - [Acute coronary syndrome: ST-segment elevation infarct].
AB  - Management of acute myocardial infarction in patients presenting with ST-segment
      elevation has evolved considerably over the past decades. In this review, we will
      limit the discussion to STEMI, and describe some recent developments and new
      insights into the evidence base of various therapeutic options. We will address
      the contemporary antithrombotic approach to treatment of this disorder. The
      controversy regarding optimal treatment of ACS, whether invasive or conservative,
      is discussed. This seems all the mandatory more as many study populations are not
      directly comparable, and some therapies are nowhere at hand. Progressively
      important cost-benefit considerations are another aspect that makes the
      assessment of the evidence claimed difficult.

PMID- 14655634
TI  - [The ideal home for the aged].

PMID- 14655635
TI  - Diagnostic and prognostic utility of rapid strip (OptiMal and Paracheck) versus
      conventional smear microscopy in adult patients of acute, uncomplicated P.
      falciparum malaria in Mumbai, India.
AB  - OBJECTIVES: The present study compared the diagnostic and prognostic utility of
      two rapid tests the (Paracheck and OptiMal) versus conventional smear microscopy.
      METHODS: Using two independent microscopists we carried out the three tests in 31
      adult cases of smear positive, acute, uncomplicated Plasmodium falciparum
      malaria. All three tests were done pretreatment, and on Days 8, 15 and 29.
      RESULTS: Compared to microscopy, the Paracheck had a sensitivity of 100%, while
      the OptiMal had a sensitivity of 83.7%. The lower sensitivity of OptiMal resulted
      from misidentification by both microscopists of 6/31 cases as Plasmodium vivax.
      As a follow up tool, the OptiMal was better than Paracheck, due to the earlier
      disappearance of the parasite LDH. Also in the Paracheck, between microscopists,
      there was a significant difference in reading the tests, on Days 8 and 15.
      CONCLUSION: Our study reiterates, the continued utility of conventional smear
      microscopy.

PMID- 14655636
TI  - [Great advances due to third generation prostheses--skillful ankle joint instead
      of bracing].

PMID- 14655637
TI  - [Brain and head injury. Part 1: Clinical classification, imaging modalities,
      extra-axial injuries, and contusions].
AB  - This article describes the imaging tools for efficient diagnostic management of
      head trauma victims. The basic mechanisms of brain injuries are explained and the
      imaging features are described. Computed tomography remains the most important
      method for the initial screening and follow-up investigation. Though magnetic
      resonance imaging has a higher sensitivity to most traumatic lesions, it does not
      play an important role in the acute phase of head trauma patients. In the first
      part of this paper clinical classifications, imaging modalities, extra-axial
      injuries, and contusions are described. In the second part of this paper intra
      axial and secondary injuries are discussed.

PMID- 14655638
TI  - [Infectiology--a central topic in urology].

PMID- 14655639
TI  - [Proven and unproven hygiene measures in urology].
AB  - In urology, catheter-associated urinary tract infections are most common, and
      postoperative wound infections the second most common nosocomial infections. This
      article gives an overview of standard hygiene measures, but focuses on proven and
      unproven hygiene measures for preventing catheter-associated urinary tract
      infections and postoperative wound infections. Consistent implementation of these
      measures contributes to minimizing infection rates and to establishing a quality
      standard, whereby surveillance of nosocomial infections contributes substantially
      to internal quality assurance.

PMID- 14655641
TI  - [Green urine. A case report and review of the literature].
AB  - Green urine, a well described condition, can be caused by a variety of agents.
      Here we describe a case of green urine caused by blue food colouring during tube
      feeding. In the article, we list more than 20 drugs, chemical agents and
      microorganisms which have been associated with green urine.

PMID- 14655640
TI  - [Prostate massage with unwanted consequences. Case report].
AB  - We report a case in which a regular prostate massage (chronic prostatitis) turned
      into a life-threatening event. After the prostate massage, an enormous
      periprostatic hemorrhage developed. During hospitalization the patient developed
      an embolic insult to the lungs. To our knowledge no ther cases have been
      published. This report shows the potentially serious consequences, and we
      conclude that any pain after prostate massage needs further diagnostic steps
      (ultrasound, CT scan).

PMID- 14655642
TI  - Ethical issues in ageing and biography.
AB  - The increasing use of biographical materials in research and intervention in the
      field of ageing gives rise to significant ethical issues. In this inquiry, four
      of these issues are explicated. First, the notion of informed consent is explored
      in relation to selected contexts of research and intervention in ageing and
      biography. Second, the issues of autonomy and competence are considered from the
      point of view of identifying contexts where biography is a prerequisite for
      ethically responsive action. The third ethical issue concerns respecting the
      groundrules of various biographical approaches. Finally, the notions of
      authenticity and truth in lifestories are explored in an attempt to clarify the
      limitations and expectations of ageing and biography. The discussion of these
      ethical issues proceeds on the basis of an argument that indicates the
      fundamental importance of biographical ageing or the stories we are.

PMID- 14655643
TI  - Ethics and publication.

PMID- 14655644
TI  - [Antibiotic prophylaxis in transrectal prostate biopsy. Short-term vs. long-term
      therapy].

PMID- 14655645
TI  - [What is the function of estrogen receptors in the prostate?].

PMID- 14655646
TI  - [Diagnostic and therapeutic procedures for hemospermia].
AB  - In general, hemospermia represents a trivial condition: nevertheless, it is often
      alarming for the patient and his partner. Although differential diagnosis is
      comprehensive, the most frequent underlying causes are infection and inflammatory
      processes in the lower seminal passages. Cases of primary and solitary
      hemospermia can be adequately assessed by urinalysis, blood pressure measurement,
      and reassurance of the patient. Persistent and recurrent cases of hemospermia are
      best clarified by transrectal ultrasound examination, cystoscopy, and magnetic
      resonance imaging. Treatment is based on the examination results.

PMID- 14655647
TI  - [Italian Society of Reference Values 4th National Congress. 14-16 December 2000].

PMID- 14655648
TI  - ["Kidney transplantation" Professional Group of the Graduate and Continuing
      Education Committee of German Urologists. Report of the 10th annual meeting of
      the Professional Group 27 - 29 June 2002 in Halle/Saale].

PMID- 14655649
TI  - [Health policy in Germany: attitude of German citizens. Results of a survey
      requested by the Federal Minister of Health].

PMID- 14655650
TI  - [Key points of reform of the German health service 2003+. From the viewpoint of
      the Society of Private Practice Accounting Services].

PMID- 14655651
TI  - [References and information on the EMB-2000plus concept].

PMID- 14655652
TI  - [Hot topic: EuGH decision, work schedule regulation, continuing education.
      Presented at the 16th Surgeons Day, Cologne 4-5 October 2002].

PMID- 14655653
TI  - [Karlsruhe work schedule mode. "Introduction of the 4 day work week with full
      wages"].

PMID- 14655654
TI  - [Quality circles in urology].

PMID- 14655655
TI  - [ADHD in adulthood--guidelines based on expert consensus with DGPPN support].

PMID- 14655656
TI  - [Comment on "Planning ambulatory rehabilitation in psychiatric and psychosomatic
      disorders"].

PMID- 14655657
TI  - The role of EMS in public access defibrillation.

PMID- 14655659
TI  - Antibiotic development pipeline runs dry. New drugs to fight resistant organisms
      are not being developed, experts say.

PMID- 14655658
TI  - US panel urges caution on testosterone therapy. Large-scale trials of efficacy
      and safety are needed before widespread use can be recommended.

PMID- 14655660
TI  - AIDS vaccine fails in Thai trial.

PMID- 14655661
TI  - South Africa boosts funding for HIV/AIDS.

PMID- 14655662
TI  - [Prophylactic drug management of migraine].
AB  - Migraine prophylaxis with drugs is still an essential part of migraine therapy.
      This is especially true for those patients with frequent migraines who are in
      danger of developing drug-induced headaches. Migraine prophylaxis should be taken
      in consideration in patients who suffer from 7 or more migraine days per month in
      spite of all non-pharmacological efforts. When choosing a prophylactic drug not
      only efficacy but tolerability and safety for long-term intake should be
      considered. Prophylactic drugs used to be classified as drugs of first, second
      and third choice. According to this step care model treatment was started with a
      drug of first choice and only in case of lack of efficacy or adverse events a
      drug of lower choice was selected. Today, in contrast to the traditional step
      care a stratified care is favored. Treatment is individualized based on an
      assessment of the patients' medical needs, on comorbidity, the migraine phenotype
      and most importantly the individual situation of the patient in life. The paper
      gives an overview of the efficacy and tolerability of drugs used in migraine
      prophylaxis.

PMID- 14655663
TI  - Global Fund approves grants to fight HIV/AIDS in Russia.

PMID- 14655664
TI  - Canada delays legislation on cheap drugs.

PMID- 14655665
TI  - Maker of vitamin B1-deficient baby milk admits error.

PMID- 14655666
TI  - WHO steps up campaign on counterfeit drugs.

PMID- 14655667
TI  - Research by US psychiatrists in danger of extinction. Expert committee recommends
      steps to strengthen research training in psychiatry residency.

PMID- 14655668
TI  - [Addressed to the Federal Professional Society of Rehabilitation on "Planning
      ambulatory rehabilitation of psychosomatic and psychiatric diseases" 15 January
      2003].

PMID- 14655669
TI  - [Planning ambulatory rehabilitation of psychiatric and psychosomatic disorders.
      Position on the 15 January 2003 plan].

PMID- 14655671
TI  - Bibliography. Luminescence literature. Firefly bioluminescence.

PMID- 14655670
TI  - Bibliography. Luminescence literature. Bioluminescent fusion proteins.

PMID- 14655672
TI  - Bibliography. Luminescence literature. Bioluminescence resonance energy transfer
      assays.

PMID- 14655673
TI  - Nursing home care of individuals with multiple sclerosis: guidelines &
      recommendations for quality care. Guidelines and standards for care.

PMID- 14655675
TI  - Biological properties of sulfated fucans: the potent inhibiting activity of algal
      fucoidan against the human compliment system.

PMID- 14655676
TI  - Can paediatric radiologists resist RECIST (response evaluation criteria in solid
      tumours)?

PMID- 14655677
TI  - Pyriform sinus fistula causing a neck abscess.

PMID- 14655678
TI  - More on organizational changes.

PMID- 14655679
TI  - Therapy for HDV!

PMID- 14655680
TI  - A new survival trick of hepatitis C virus: blocking the activation of interferon
      regulatory factor-3.

PMID- 14655681
TI  - Proceedings of the IV Congress of Veterinary Immunology. 11-12 September 2003.

PMID- 14655682
TI  - Resistance of HBV to adefovir dipivoxil: a case for combination antiviral
      therapy?

PMID- 14655683
TI  - Giant occipital intracranial and extracranial meningioma.

PMID- 14655684
TI  - Tumors of the Liver and Pancreas. September 20-21, 2002, Dachau, Germany.
      Abstracts.

PMID- 14655686
TI  - The 10th Annual Winter Workshop and Meeting of the Canadian Rheumatology
      Association. Mont Tremblant, Quebec, Canada. February 26-March 1, 2003.
      Abstracts.

PMID- 14655685
TI  - Proceedings of the 5th International Symposium on Avian Influenza. Athens,
      Georgia, USA. April 14-17, 2002.

PMID- 14655687
TI  - ["Current Issues in Hematology 2002" continuing education course--review and
      prospects for the future].

PMID- 14655688
TI  - Resistance 2001: Meeting the Challenge. Harpenden, Herts, United Kingdom. 24-26
      September 2001. Conference proceedings.

PMID- 14655689
TI  - Literature watch. January-June 2003.

PMID- 14655690
TI  - Transcription of live discussion: Alzheimer genes in cortical development: how do
      their prenatal functions relate to dementia?

PMID- 14655691
TI  - [Hypercalcemia].

PMID- 14655692
TI  - Assessment of potential carbon dioxide reductions due to biomass-coal cofiring in
      the United States.
AB  - Cofiring biomass with coal in existing power plants offers a relatively
      inexpensive and efficient option for increasing near-term biomass energy
      utilization. Potential benefits include reduced emissions of carbon dioxide,
      sulfur, and nitrogen oxides and development of biomass energy markets. To
      understand the economics of this strategy, we develop a model to calculate
      electricity and pollutant mitigation costs with explicit characterization of
      uncertainty in fuel and technology costs and variability in fuel properties. The
      model is first used to evaluate the plant-level economics of cofiring as a
      function of biomass cost. It is then integrated with state-specific coal
      consumption and biomass supply estimates to develop national supply curves for
      cofire electricity and carbon mitigation. A delivered cost of biomass below 15
      dollars per ton is required for cofire to be competitive with existing coal-based
      generation. Except at low biomass prices (less than 15 dollars per ton), cofiring
      is unlikely to be competitive for NOx or SOx control, but it can provide
      comparatively inexpensive control of CO2 emissions: we estimate that emissions
      reductions of 100 Mt-CO2/year (a 5% reduction in electric-sector emissions) can
      be achieved at 25 +/- 20 dollars/tC. The 2-3 year time horizon for deployment-
      compared with 10-20 years for other CO2 mitigation options--makes cofiring
      particularly attractive.

PMID- 14655693
TI  - Evidence for a specific pattern of polychlorinated dibenzo-p-dioxins and
      dibenzofurans in bivalves.
AB  - The occurrence of the polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans (PCDDs/PCDFs) was studied in four different bivalve species
      (mussels, oysters, carpetshells, and cupped oysters) collected in three different
      sampling stations at the Spanish Coast from 1994 onward. The analysis revealed an
      unexpected isomer distribution of chlorosubstituted dioxins and furans
      characterized by a complex mixture of TCDF and TCDD, including both toxic and
      nontoxic isomers and highly chlorinated congeners, mainly OCDD. Principal
      component analysis revealed similarities between identical species collected from
      the different sites. A dioxin fingerprint could be easily distinguished between
      bivalve species collected in the same sampling point. The dioxin fingerprint
      found in filter-feeders was also compared to other marine species showing
      remarkable differences. Due to the habits of the bivalve species, sediment
      samples were also analyzed within this study. No similarities in the pattern were
      found for both matrices, the sediments and the bivalves. In the absence of a
      potential source of these toxicants affecting these species the hypothesis of a
      specific metabolism of the bivalves is suggested. No values higher than 4 pg WHO
      TEQ/g whole weight were determined, and all samples met the current limit
      proposed by European Regulations. Independently of the bivalve species
      considered, the major contribution to the total WHO-TEQ comes from 2,3,7,8-TCDF
      and 2,3,4,7,8-PeCDF, at about the same levels of the 2,3,7,8-TCDD and 1,2,3,7,8
      PCDD.

PMID- 14655694
TI  - Emissions reductions as a result of automobile improvement.
AB  - Remote sensing of light duty vehicle on-road tailpipe exhaust has been used to
      measure on-road mass emissions of automobile fleets in Denver for 13 years and in
      two other U.S. cities for 5 years. Analysis of these fleets shows that newer
      automobiles, during a period of fairly constant new car standards, have become
      continually less polluting independent of measurement location. Improving
      emissions control technology spurred by federal regulations is thought to have
      brought about these trends.

PMID- 14655695
TI  - Mercury speciation by X-ray absorption fine structure spectroscopy and sequential
      chemical extractions: a comparison of speciation methods.
AB  - Determining the chemical speciation of mercury in contaminated mining and
      industrial environments is essential for predicting its solubility, transport
      behavior, and potential bioavailability as well as for designing effective
      remediation strategies. In this study, two techniques for determining Hg
      speciation--X-ray absorption fine structure (XAFS) spectroscopy and sequential
      chemical extractions (SCE)--are independently applied to a set of samples with Hg
      concentrations ranging from 132 to 7539 mg/kg to determine if the two techniques
      provide comparable Hg speciation results. Generally, the proportions of insoluble
      HgS (cinnabar, metacinnabar) and HgSe identified by XAFS correlate well with the
      proportion of Hg removed in the aqua regia extraction demonstrated to remove HgS
      and HgSe. Statistically significant (>10%) differences are observed however in
      samples containing more soluble Hg-containing phases (HgCl2, HgO, Hg3S2O4). Such
      differences may be related to matrix, particle size, or crystallinity effects,
      which could affect the apparent solubility of Hg phases present. In more highly
      concentrated samples, microscopy techniques can help characterize the Hg-bearing
      species in complex multiphase natural samples.

PMID- 14655696
TI  - Hygroscopic properties of two model humic-like substances and their mixtures with
      inorganics of atmospheric importance.
AB  - Water-soluble macromolecular polyacids can play a potentially important role in
      the hygroscopic properties of atmospheric aerosols. These acids have molecular
      structures similar to natural fulvic acids (FA) (or humic acids) and are referred
      to as humic-like substances (HULIS). In this study, the hygroscopicity of HULIS
      and the mixture of HULIS and sodium chloride (NaCl) and that of HULIS and
      ammonium sulfate (AS) aerosols at a mass ratio of 1:1 are studied using two
      natural FA: the Nordic Aquatic Fulvic Acid (NAFA) and the Suwannee River Fulvic
      Acid (SRFA) as model compounds in an electrodynamic balance. NAFA and SRFA both
      absorbed and desorbed water reversibly without crystallization and retained water
      at a relative humidity (RH) < 10%. NAFA and SRFA have a mass growth ratio of 1.25
      and 1.45 from RH = 10% to RH = 90%, respectively. However, these results are
      different from those of another natural FA (the Nordic River Fulvic Acid
      Reference) in the literature. The differences are possibly due to the differences
      in the chemical composition of the natural FA, which depends on their sources and
      the isolation methods. These results suggest that a standardization of the
      isolation methods of HULIS is needed for better understanding of their
      atmospheric properties and environmental impacts. In general, the deliquescence
      and crystallization RH of FA-inorganic mixtures are comparable with those of
      their respective pure inorganic species. Since FA are less hygroscopic than NaCl
      and AS, all mixtures absorb less water compared to their respective pure
      inorganic species of equal particle mass. The FA-AS mixtures have a larger water
      uptake than the sum of those of the FA and AS individually following a simple
      additivity rule as noninteracting species at RH = 90%. This enhancement effect
      increases as the RH decreases. There is no such enhancement effect for the FA
      NaCl mixtures until RH is below 90%. These results reveal that the effect of the
      interactions between FA and inorganic species on the water uptake of the
      mixtures, in general, is a function of RH.

PMID- 14655697
TI  - Transport dynamics in a sheltered estuary and connecting tidal straits: SF6
      tracer study in New York Harbor.
AB  - In July 2002, approximately 0.9 mol of sulfur hexafluoride (SF6) was injected
      into Newark Bay, NJ, a 14 km2 estuary that forms part of New York Harbor, to
      investigate circulation, mixing, and the transport and fate of solutes. The SF6
      tracer was observed over 11 consecutive days using a high-resolution measurement
      system. Total tracer mass in the sheltered waters declined quasiexponentially at
      a rate of 0.29 +/- 0.03 d(-1). Air-water gas exchange was estimated to account
      for 56% of tracer mass loss, upon the basis of wind speed/gas exchange
      parametrizations. Large-scale tidal transfer of solutes through the Kill van Kull
      strait (7 km long) caused net seaward flushing contrary to the apparent residual
      circulation. Seaward transport via the Arthur Kill strait (20 km long) appeared
      to depend on longitudinal dispersion, residual circulation, and freshwater
      discharge and was approximately 1 order of magnitude lower. The loss rate due to
      flushing alone was 0.13 +/- 0.02 d(-1), indicating a mean residence time for
      water and solutes in Newark Bay of approximately 8 days (without gas exchange).
      The experiment provides direct visualization of the transport of a released
      contaminant, and suggests a relationship between the length and configuration of
      tidal straits and related transport of solutes.

PMID- 14655698
TI  - Biogeochemical processes and microbial characteristics across groundwater-surface
      water boundaries of the Hanford Reach of the Columbia River.
AB  - Biogeochemical processes within riverbed hyporheic zones (HZ) can potentially
      impact the fate and transport of contaminants. We evaluated a modified freeze
      core technique for the collection of intact cobble-bed samples from the Columbia
      River HZ along a stretch of the Hanford Reach in Washington State and
      investigated microbiological and geochemical parameters of corresponding frozen
      and unfrozen samples. During three sampling periods (March, May, and November
      2000), relatively high numbers of viable aerobic heterotrophic bacteria were
      recovered from both unfrozen (10(6)-10(7) cfu/g) and frozen samples (10(5)-10(6)
      cfu/g). Relatively large populations of sulfate-, nitrate-, and iron-reducing
      bacteria were present, and significant concentrations of acid-volatile sulfide
      were measured in some samples, indicating that anoxic regions exist within this
      zone. Cr(VI), a priority groundwater pollutant on adjacent U.S. Department of
      Energy lands, was probably removed from solution in HZ samples by a combination
      of microbial activity and chemical reduction, presumably via products of
      anaerobic microbial metabolism. These results suggest that biogeochemical
      processes in the Columbia River HZ may contribute to the natural attenuation of
      Cr(VI). Although freezing modestly diminished recovery of viable bacteria, freeze
      core techniques proved reliable for the collection of intact hyporheic sediments.

PMID- 14655699
TI  - Source apportionment of PM2.5 at an urban IMPROVE site in Seattle, Washington.
AB  - The multivariate receptor models Positive Matrix Factorization (PMF) and Unmix
      were used along with the EPA's Chemical Mass Balance model to deduce the sources
      of PM2.5 at a centrally located urban site in Seattle, WA. A total of 289 filter
      samples were obtained with an IMPROVE sampler from 1996 through 1999 and were
      analyzed for 31 particulate elements including temperature-resolved fractions of
      the particulate organic and elemental carbon. All three receptor models predicted
      that the major sources of PM2.5 were vegetative burning (including wood stoves),
      mobile sources, and secondary particle formation with lesser contributions from
      resuspended soil and sea spray. The PMF and Unmix models were able to resolve a
      fuel oil combustion source as well as distinguish between diesel emissions and
      other mobile sources. In addition, the average source contribution estimates via
      PMF and Unmix agreed well with an existing emissions inventory. Using the
      temperature-resolved organic and elemental carbon fractions provided in the
      IMPROVE protocol, rather than the total organic and elemental carbon, allowed the
      Unmix model to separate diesel from other mobile sources. The PMF model was able
      to do this without the additional carbon species, relying on selected trace
      elements to distinguish the various combustion sources.

PMID- 14655700
TI  - Capacity for biodegradation of CFCs and HCFCs in a methane oxidative counter
      gradient laboratory system simulating landfill soil covers.
AB  - The attenuation of methane and four chlorofluorocarbons was investigated in a
      dynamic methane and oxygen counter-gradient system simulating a landfill soil
      cover. Soil was sampled at Skellingsted Landfill, Denmark. The soil columns
      showed a high capacity of methane oxidation with oxidation rates of 210 g m(-2)
      d(-1) corresponding to a removal efficiency of 81%. CFC-11 and to a lesser extent
      also CFC-12 were degraded in the active soil columns. The average removal
      efficiency was 90% and 30% for CFC-11 and CFC-12, respectively. Soil gas
      concentration profiles indicated that the removal was due to anaerobic
      degradation, which was verified in anaerobic batch experiments where CFC-11 was
      rapidly degraded. HCFC-21 and HCFC-22 were also degraded in active soil columns
      (61% and 41%, respectively), but compared to the CFCs, the degradation was
      located in the upper oxic part of the column with overlapping gradients of
      methane and oxygen. High oxidation rates of methane and HCFCs were obtained in
      soil microcosms incubated with methane. When increasing the column inlet flow,
      the oxidation zone was moved upward in the column, and the removal efficiency of
      methane and HCFCs decreased. The removal of CFCs was, however, less affected
      since the anaerobic zone expanded with increasing inlet flow rates. This study
      demonstrates the complexity of landfill soil cover systems and shows that both
      anaerobic and aerobic bacteria may play a very important role in reducing the
      emission of not only methane but also trace components into the atmosphere.

PMID- 14655701
TI  - Comparative oxidation and net emissions of methane and selected non-methane
      organic compounds in landfill cover soils.
AB  - The surface emissions of methane (CH4) and non-methane organic compounds (NMOCs)
      were determined at two different areas at a French landfill: a permanently
      covered and fully vegetated area (40 cm coarse sand + 80 cm of loam) and a
      temporarily covered area (40 cm of coarse sand). The 37 NMOCs quantified in the
      landfill gas samples included alkanes (C1-C10), alkenes (C1-C4), halogenated
      hydrocarbons (including (H)CFCs), and aromatic hydrocarbons. Both positive and
      negative CH4 fluxes ranging from -0.01 to 0.008 g m(-2) d(-1) were measured from
      the permanently covered cell. However, high spatial variation was observed, and a
      hot spot with a high flux (10 g m(-2) d(-1)) was identified. A higher CH4
      emission occurred from the temporarily covered cell (CH4 flux of 49.9 g m(-2) d(
      1)) as compared to the permanently covered cell. The NMOC fluxes from the
      permanently covered zone were all very small with both positive and negative
      fluxes in the order of 10(-7) to 10(-5) g m(-2) d(-1). Higher and mainly positive
      NMOC fluxes in the order of 10(-5) to 10(-4) g m(-2) d(-1) were obtained from the
      temporarily covered zone. The lower emission from the permanently covered and
      fully vegetated cell was attributable to the thicker soil layer, which functions
      as microbial habitat for methanotrophic bacteria. The NMOC oxidation capacity was
      investigated in soil microcosms incubated with CH4. Maximal oxidation rates for
      the halogenated aliphatic compounds varied between 0.06 and 8.56 microg (g of
      soil)(-1) d(-1). Fully substituted hydrocarbons (tetrachloromethane,
      perchloroethylene, CFC-11, CFC-12, and CFC-113) were not degraded in the presence
      of CH4 and O2. Benzene and toluene were rapidly degraded, giving very high
      maximal oxidation rates (28 and 39 microg (g of soil)(-1) d(-1)). On the basis of
      the emission measurements and the batch experiments conducted, a general pattern
      was observed between emissions and biodegradability of various NMOCs. The
      emissions mainly consisted of compounds that were not degradable or slowly
      degradable, while an uptake of easily degradable compounds was registered. As an
      example, perchloroethylene, trichloromethane, CFC-11, and CFC-12 were emitted,
      while atmospheric consumption of aromatic hydrocarbons and lower chlorinated
      hydrocarbons such as vinyl chloride, dichloromethane, and chloromethane was
      observed. This study demonstrates that landfill soil covers show a significant
      potential for CH4 oxidation and co-oxidation of NMOCs. Under certain conditions,
      landfills may even function as sinks for CH4 and selected NMOCs, like aromatic
      hydrocarbons and lower chlorinated compounds.

PMID- 14655702
TI  - Acid-base properties of brown seaweed biomass considered as a Donnan gel. A model
      reflecting electrostatic effects and chemical heterogeneity.
AB  - Brown seaweeds are interesting materials to be used as biosorbents for heavy
      metals due to their high binding ability and low cost. The study of the passive
      biosorption of protons on this kind of materials and its dependency on pH, ionic
      strength, and medium composition is essential for the practical application of
      brown algae in wastewater treatment. This work reports the results of the study
      of the proton binding equilibria of dead biomass from the seaweeds Sargassum
      muticum, Cystoseira baccata, and Saccorhiza polyschides by potentiometric
      titration with a glass electrode in the pH range between 2 and 8. Two different
      salts, NaCl and KNO3, in concentrations ranging from 0.05 to 2 mol x L(-1), were
      used as background electrolytes. The influence of the ionic strength was
      accounted for by means of the Donnan model in combination with the master curve
      approach. Different empirical expressions to describe the swelling behavior of
      the biosorbent were tested. On the basis of the intrinsic affinity distribution
      analysis a unimodal Langmuir-Freundlich isotherm was selected to describe the
      proton binding properties. The results show very little influence of the type of
      salt. The ionic strength dependency of the proton binding is very similar for the
      three species, and average empirical expressions of the Donnan volume are
      proposed. The maximum proton binding capacities obtained ranged between 2.4 and
      2.9 mol x kg(-1), with average intrinsic proton affinity constants between 3.1
      and 3.3, and heterogeneity parameters of ca. 0.5 for S. muticum and C. baccata,
      and slightly higher (ca. 0.7) for S. polyschides. The combined Langmuir
      Freundlich equation and Donnan model allowed a good description of the
      experimental charge vs pH curves obtained.

PMID- 14655703
TI  - "Humic coverage index" as a determining factor governing strain-specific
      hydrocarbon availability to contaminant-degrading bacteria in soils.
AB  - We report development of a novel parameter for quantifying the amount of humic
      and fulvic acids per unit surface area in a particular soil. This quantity, the
      "humic coverage index" (HCI), provides a measurement of the relative spatial
      extents and/or thicknesses of the humic/fulvic overlayers in different soils,
      and, therefore, can be used in modeling various soils' behavior in sequestration
      processes in which humic materials are involved. HCI is herein applied to
      modeling biodegradation of aromatic and aliphatic hydrocarbons (phenanthrene,
      pyrene, and hexadecane) by several bacterial strains. Results indicate that, for
      the cases studies here, contaminant biodegradation is highest at a particular HCI
      and decreases if the coverage density of humic material is lower or higher than
      this optimum value. The HCI value at which maximal degradation was observed
      varied across different strains (indicating strain-specific differences in
      ability to degrade contaminants sorbed to humic materials) and, to a lesser
      extent, across different contaminants. The HCI concept is also demonstrated to be
      useful in explaining soil-, strain-, and contaminant-specific variations in the
      ability of fulvic acid supplementation to enhance contaminant biodegradation.
      Finally, we show that, in general, strains which are comparatively better at
      degrading contaminants in high-HCI soils also show enhanced contaminant
      mineralization in vitro in the presence of humic acids, such as when hydrocarbons
      are adsorbed onto these materials.

PMID- 14655705
TI  - Leaching potential of persistent soil fumigant residues.
AB  - Persistent fumigant residues in soil resulting from agricultural pest-control
      practices may be released into water and leached to groundwater. In this study,
      the leaching potential of persistent soil fumigant residues was evaluated, and
      the effect of dissolved organic matter (DOM) and ammonium thiosulfate (ATS)
      amendment was investigated. A silt loam soil was incubated separately with the
      fumigants 1,3-dichloropropene (1,3-D), chloropicrin (CP), and methyl
      isothiocyanate (MITC) at 240-990 mg kg(-1) for 35 d, followed by 48 h of
      evaporation. The soil was packed into stainless steel columns (1.4 cm x 10 cm)
      and leached with water, 5 mM ATS, and DOM solution (DOC 250 mg L(-1)) by gravity.
      Residues of 1,3-D, CP, and MITC in the evaporated soil were 5.61, 11.38, and 1.83
      mg kg(-1), respectively. Concentrations of 1,3-D, CP, and MITC in column
      effluents ranged from 0.05 to 0.73, 0.16 to 0.81, and 0.05 to 0.27 mg L(-1),
      respectively, when the soil was leached with 10 pore volumes of water. DOM did
      not promote the leaching of persistent fumigant residues, and ATS remarkably
      reduced the amount of 1,3-D and CP yet notably increased MITC recovered in the
      effluents. The results suggest that the leaching of persistent fumigant residues
      through soil to water is significant, and movement of fumigants in soil is not
      facilitated by DOM. Amending soil with ATS through irrigation is an effective
      method to remove persistent residues of halogenated fumigants. To reduce
      groundwater pollution risks posed by fumigation, persistent soil fumigant
      residues have to be considered.

PMID- 14655704
TI  - Virus inactivation in aluminum and polyaluminum coagulation.
AB  - Inorganic aluminum salts, such as aluminum sulfate, are coagulants that cause
      small particles, such as bacteria and viruses as well as inorganic particles, to
      destabilize and combine into larger aggregates. In this investigation, batch
      coagulation treatments of water samples spiked with Qbeta, MS2, T4, and P1
      viruses were conducted with four different aluminum coagulants. The total
      infectious virus concentration in the suspension of floc particles that
      eventually formed by dosing with coagulant was measured after the floc particles
      were dissolved by raising the pH with an alkaline beef extract solution. The
      virus concentrations were extremely reduced after the water samples were dosed
      with aluminum coagulants. Viruses mixed with and adsorbed onto preformed aluminum
      hydroxide floc were, however, completely recovered after the floc dissolution.
      These results indicated that the aluminum coagulation process inactivates
      viruses. Virucidal activity was most prominent with the prehydrolyzed aluminum
      salt coagulant, polyaluminum chloride (PACl). Virucidal activity was lower in
      river water than in ultrapure water--natural organic matter in the river water
      depressed the virucidal activity. Mechanisms and kinetics of the virus
      inactivation were discussed. Our results suggest that intermediate polymers
      formed during hydrolysis of the aluminum coagulants sorbed strongly to viruses,
      either rendering them inactive or preventing infectivity.

PMID- 14655706
TI  - The relative effectiveness of pH control and heat treatment for enhancing
      biohydrogen gas production.
AB  - Hydrogen gas can be recovered from the microbial fermentation of organic
      substrates at high concentrations when interspecies hydrogen transfer to
      methanogens is prevented. Two techniques that have been used to limit
      methanogenesis in mixed cultures are heat treatment, to remove nonsporeforming
      methanogens from an inoculum, and low pH during culture growth. We found that
      high hydrogen gas concentrations (57-72%) were produced in all tests and that
      heat treatment (HT) of the inoculum (pH 6.2 or 7.5) produced greater hydrogen
      yields than low pH (6.2) conditions with a nonheat-treated inoculum (NHT).
      Conversion efficiencies of glucose to hydrogen (based on a theoretical yield of 4
      mol-H2/mol-glucose) were as follows: 24.2% (HT, pH = 6.2), 18.5% (HT, pH = 7.5),
      14.9% (NHT, pH = 6.2), and 12.1% (NHT, pH = 7.5). The main products of glucose (3
      g-COD/L) utilization (> or = 99%) in batch tests were acetate (3.4-24.1%),
      butyrate (6.4-29.4%), propionate (0.3-12.8%), ethanol (15.4-28.8%), and hydrogen
      (4.0-8.1%), with lesser amounts of acetone, propanol, and butanol (COD basis).
      Hydrogen gas phase concentrations in all batch cultures reached a maximum of 57
      72% after 30 h but thereafter rapidly declined to nondetectable levels within 80
      h. Separate experiments showed substantial hydrogen losses could occur via
      acetogenesis and that heat treatment did not prevent acetogenesis. Heat treatment
      consistently eliminated the production of measurable concentrations of methane.
      The disappearance of ethanol produced during hydrogen production was likely due
      to acetic acid production as thermodynamic calculations show that this reaction
      is spontaneous once hydrogen is depleted. Overall, these results show that low pH
      was, without heat treatment, sufficient to control hydrogen losses to methanogens
      in mixed batch cultures and suggest that methods will need to be found to limit
      acetogenesis in order to increase hydrogen gas yields by batch cultures.

PMID- 14655707
TI  - Solid-solution partitioning of Cd, Cu, Ni, Pb, and Zn in the organic horizons of
      a forest soil.
AB  - We report the solid-liquid partitioning of Cd, Cu, Ni, Pb, and Zn in 60 organic
      horizon samples of forest soils from the Hermine Watershed (St-Hippolyte, PQ,
      Canada). The mean Kd values are respectively 1132, 966, 802, 3337 and 561.
      Comparison of those Kd coefficients to published compilation values show that the
      Kd values are lower in acidic organic soil horizons relative to the overall mean
      Kd values compiled for mineral soils. But, once normalized to a mean pH of 4.4,
      the Kd values in organic soil horizons demonstrate the high sorption affinity of
      organic matter, which is either as good as or up to 30 times higher than mineral
      soil materials for sorbing trace metals. Regression analysis shows that, within
      our data set, pH and total metal contents are not consistent predictors of metal
      partitioning. Indeed, metal sorption by the solid phase must be studied in
      relation to complexation by dissolved organic ligands, and both processes may
      sometime counteract one another.

PMID- 14655708
TI  - Sorption of polycyclic aromatic hydrocarbons to oil contaminated sediment:
      unresolved complex?
AB  - Oil is ubiquitous in aquatic sediments and may affect partitioning and
      bioavailability of hydrophobic organic chemicals (HOCs). In contrast to other
      sedimentary hydrophobic carbon phases (natural organic matter, soot-like
      materials), oil residues have hardly received any attention as far as it concerns
      effects on HOC sorption. This paper describes experimental work dealing with such
      effects of oil on polycyclic aromatic hydrocarbon (PAH) sorption to sediments.
      Three different oils were spiked to a marine sediment in concentrations between 0
      and 100 g/kg. Sediment-water distribution coefficients (Kd) for six deuterated
      PAHs were then determined either directly after spiking the oil or after a semi
      natural weathering process in the lab (lasting for more than 2 yr). Resulting Kd
      values demonstrated sorption-reducing (competitive) effects at relatively low oil
      concentrations and sorption-enhancing effects at high oil concentrations. The
      latter effects only occurred above a certain threshold [i.e., ca. 15% (w/w) of
      oil on a sedimentary organic carbon basis] marking the oil concentration at which
      the hydrocarbon mixture presumably starts forming separate phases. Assuming a two
      domain (organic carbon + oil) distribution model, oil-water distribution
      coefficients (K(oil)) for PAHs were estimated. For fresh oils, log K(oil) values
      appeared to be very similar for different types of oils, proportional to log
      K(OW) values and indistinguishable from log K(OC) values. For weathered oils,
      K(oil) values were also rather independent of the type of oil, but the affinity
      of low molecular weight PAHs for weathered oil residues appeared to be extremely
      high, even higher than values reported for most types of soot. Because affinities
      of high molecular weight PAHs for oils had not changed upon weathering, sorption
      of all PAHs studied (comprising a log K(OW) range of 4.6-6.9) to the weathered
      oil residues appeared to be more or less constant (averaged log K(oil) = 7.0 +/-
      0.24). These results demonstrate that it is crucial to take the presence of oil
      and its weathering state into account when assessing the actual fate of PAHs in
      aquatic environments.

PMID- 14655709
TI  - Accumulation of copper and zinc in periphyton in response to dynamic variations
      of metal speciation in freshwater.
AB  - Although the free ion activity model (FIAM) has been well-established in
      laboratory studies, there remains the need for field data in order to validate
      the applicability of this model in natural systems. The objective of this study
      was to investigate the response of copper and zinc accumulation in periphyton to
      short-term variations in metal concentration and speciation in freshwater. During
      heavy rain events, dissolved Cu in the Furtbach stream increased from 40 to 118
      nM, while dissolved Zn increased from 45 to 147 nM due to the release of metals
      from contaminated sediments. Increases in free copper and free zinc ions in the
      water (from 10(-14) to 10(-11.5) M for Cu2+; from 1 to 15 nM for Zn2+) were
      observed during the onset of heavy rain events. Periphytic algae collected from
      artificial substrates had an intracellular copper content (0.2-2.8 micromol/g dry
      weight (dw)) that varied as a function of the exchangeable copper in the water
      (labile form) rather than the free Cu2+. Intracellular zinc content (1.5-8.0
      micromol/g dw) was found to follow the same trend as the free zinc ion
      concentration. Adsorbed Cu and Zn on periphyton showed a very dynamic response to
      variations in dissolved metal concentration. Different concentrations of
      dissolved manganese during the two time periods may affect the accumulation of
      zinc and copper by competition for metal uptake.

PMID- 14655710
TI  - Anaerobic oxidation of crude oil hydrocarbons by the resident microorganisms of a
      contaminated anoxic aquifer.
AB  - The biodegradation of two crude oils by microorganisms from an anoxic aquifer
      previously contaminated by natural gas condensate was examined under methanogenic
      and sulfate-reducing conditions. Artificially weathered Alaska North Slope crude
      oil greatly stimulated both methanogenesis and sulfate reduction. Gas
      chromatographic analysis revealed the entire n-alkane fraction of this oil (C13
      C34) was consumed under both conditions. Naphthalene, 2-methylnaphthalene, and 2
      ethylnaphthalene were also biodegraded but only in the presence of sulfate. Alba
      crude oil, which is naturally depleted in n-alkanes, resulted in a relatively
      modest stimulation of methanogenesis and sulfate reduction. Polycyclic aromatic
      hydrocarbon biodegradation was similar to that found for the Alaska North Slope
      crude oil, but a broader range of compounds was metabolized, including 2,6
      dimethylnaphthalene and 2,7-dimethylnaphthalene in the presence of sulfate. These
      results indicate that n-alkanes are relatively labile, and their biodegradation
      in terrestrial environments is not necessarily limited by electron acceptor
      availability. Polycyclic aromatic hydrocarbons are relatively more recalcitrant,
      and the biodegradation of these substrates appeared to be sulfate-dependent and
      homologue-specific. This information should be useful for assessing the limits of
      in situ crude oil biodegradation in terrestrial environments and for making
      decisions regarding risk-based corrective actions.

PMID- 14655711
TI  - Green rust and iron oxide formation influences metolachlor dechlorination during
      zerovalent iron treatment.
AB  - Electron transfer from zerovalent iron (Fe0) to targeted contaminants is affected
      by initial Fe0 composition, the oxides formed during corrosion, and surrounding
      electrolytes. We previously observed enhanced metolachlor destruction by Fe0 when
      iron or aluminum salts were present in the aqueous matrix and Eh/pH conditions
      favored formation of green rusts. To understand these enhanced destruction rates,
      we characterized changes in Fe0 composition during treatment of metolachlor with
      and without iron and aluminum salts. Raman microspectroscopy and X-ray
      diffraction (XRD) indicated that the iron source was initially coated with a thin
      layer of magnetite (Fe3O4), maghemite (gamma-Fe2O3), and wustite (FeO). Time
      resolved analysis indicated that akaganeite (beta-FeOOH) was the dominant oxide
      formed during Fe0 treatment of metolachlor. Goethite (alpha-FeOOH) and some
      lepidocrocite (gamma-FeOOH) formed when Al2(SO4)3 was present, while goethite and
      magnetite (Fe3O4) were identified in Fe0 treatments containing FeSO4. Although
      conditions favoring formation of sulfate green rust (GR(II); Fe6(OH)12SO4)
      facilitated Fe0-mediated dechlorination of metolachlor, only adsorption was
      observed when GR(II) was synthesized (without Fe0) in the presence of metolachlor
      and Eh/pH changed to favor Fe(III)oxyhydroxide or magnetite formation. In
      contrast, dechlorination occurred when magnetite or natural goethite was amended
      with Fe(II) (as FeSO4) at pH 8 and continued as long as additional Fe(II) was
      provided. While metolachlor was not dechlorinated by GR(II) itself during a 48-h
      incubation, the GR(II) provided a source of Fe(II) and produced magnetite (and
      other oxide surfaces) that coordinated Fe(II), which then facilitated
      dechlorination.

PMID- 14655712
TI  - Application of QSTRs in the selection of a surrogate toxicity value for a
      chemical of concern.
AB  - As part of the EPA's mission to protect the environment, chemicals of concern
      (CoCs) at Superfund or other hazardous waste sites are cleaned up based on their
      potential toxicity to humans and the surrounding ecosystem. Oftentimes, there is
      a lack of experimental toxicity data to assess the health effects for a CoC in
      the literature. This research describes a method using Quantitative Structure
      Toxicity Relationships (QSTRs) for identifying a surrogate chemical for any given
      CoC. The toxicity data of the surrogate chemical can then be used to rank
      hazardous waste-site chemicals prior to cleanup decisions. A commercial QSTR
      model, TOPKAT, was used to establish structural and descriptor similarity between
      the CoC and the compounds in the QSTR model database using the Oral Rat Chronic
      LOAEL model. All database chemicals within a similarity distance of < or = 0.200
      from the CoC are considered as potential surrogates. If the CoC fails to satisfy
      model considerations for the LOAEL model, no surrogate is suggested. Potential
      surrogates that have toxicity data on Integrated Risk Information System (IRIS),
      Health Effects Assessment Summary Tables (HEAST), or National Center for
      Environmental Assessment (NCEA) provisional toxicity value list become candidate
      surrogates. If more than one candidate surrogate is identified, the chemical with
      the most conservative RfD is suggested as the surrogate. The procedure was
      applied to determine an appropriate surrogate for dichlorobenzophenone (DCBP), a
      metabolite of chlorobenzilate, dichlorodiphenyltrichloroethane, and dicofol.
      Forty-seven potential surrogates were identified that were within the similarity
      distance of < or = 0.200, of which only five chemicals had an RfD on IRIS, HEAST,
      or on the NCEA provisional toxicity value list. Among the five potential
      surrogates, chlorobenzilate with an RfD of 2 x 10(-2) mg/kg-day was chosen as a
      surrogate for DCBP as it had the most conservative toxicity value. This compared
      well with surrogate selection using available metabolic information for DCBP and
      its metabolites or parent compounds in the literature and the provisional
      toxicity value of 3 x 10(-2) mg/kg-day that NCEA developed using a subchronic
      study.

PMID- 14655713
TI  - Regional modeling of the atmospheric fate and transport of benzene and diesel
      particles.
AB  - The Community Multiscale Air Quality model (CMAQ) was modified to simulate the
      atmospheric fate and transport of benzene and diesel particles. We simulated the
      July 11-15, 1995 period over a domain covering the eastern United States with a
      12-km horizontal resolution and a finer (4 km) resolution over a part of the
      northeastern United States that includes Washington, DC and New York City. The
      meteorological fields were obtained from a simulation conducted earlier with the
      mesoscale model MM5. Gridded emission files for benzene and diesel particles were
      developed using the SMOKE modeling system. The results of the model simulations
      showed that benzene concentrations were commensurate with available measurements.
      Over the 4-km resolution domain, a comparison between simulated and measured 24-h
      average concentrations showed a fractional error of 0.46, a fractional bias of
      0.14, and a coefficient of determination (r2) of 0.25. A comparison between
      simulated benzene hourly concentrations in New York City and in the Brigantine
      Wilderness Area, NJ, showed that urban concentrations were greater than the
      remote area concentrations by a factor of 2-5. The results of the diesel particle
      simulations showed spatial and temporal patterns that were similar to those
      obtained for benzene. However, because of the lesser contribution of on-road
      mobile sources to diesel particle emissions compared to benzene emissions, diesel
      particle concentrations showed stronger gradients between urban areas and remote
      areas. A comparison between diesel particle concentrations in New York City and
      in the Brigantine Wilderness Area, NJ, showed that the urban concentrations were
      greater than the remote area concentrations by a factor of 2-10. Assuming that
      diesel particles consist of 50% "elemental" carbon (EC), the simulated EC
      concentrations were in close agreement (within 10%) with the measured
      concentration in the urban area (Washington, DC) but were significantly lower
      than the measured EC concentrations in the remote area (Brigantine Wilderness
      Area). This result suggests that other sources beside diesel fuel engines
      contribute to atmospheric EC concentrations and that EC may not be a good
      surrogate for diesel particles. A comparison of both benzene and diesel particle
      simulated concentrations between an urban area (New York City) and a remote area
      (Brigantine Wilderness Area) shows that, at a spatial resolution of 4 km, the
      regional background may contribute from 10 to 20% to the peak concentrations.
      These results suggest that the regional background may not be negligible and
      should be taken into account in urban air toxics studies.

PMID- 14655714
TI  - Europium uptake and partitioning in oat (Avena sativa) roots as studied by laser
      induced fluorescence spectroscopy and confocal microscopy profiling technique.
AB  - The uptake of Eu3+ by elongating oat roots was studied by fluorescence
      spectroscopy, fluorescence lifetime measurement, and a laser excitation time
      resolved confocal fluorescence profiling technique. The results of this work
      indicated that initial uptake of Eu3+ was highest within the undifferentiated
      cells of the root tip just behind the root cap, a region of maximal cell growth
      and differentiation and with incomplete formation of the Casparian strip around
      the central vascular cylinder. Distribution of assimilated Eu3+ within the root's
      differentiation and elongation zone was nonuniform. Higher concentrations of Eu3+
      were observed within the vascular cylinder, specifically in the phloem and
      developing xylem parenchyma. Elevated levels of the metal were also observed in
      the root hairs of the mature root zone. Fluorescence spectroscopic
      characteristics of the assimilated Eu3+ suggested that the Eu3+ exists as inner
      sphere mononuclear complexes inside the root. This work also demonstrated the
      effectiveness of a time-resolved Eu3+ fluorescence spectroscopy and confocal
      fluorescence profiling techniques for the in vivo, real-time study of metal
      [Eu3+] accumulation by a functioning intact plant root. This approach can prove
      valuable for basic and applied studies in plant nutrition and environmental
      uptake of actinide radionuclides.

PMID- 14655715
TI  - Use of multiwavelength transmission spectroscopy for the characterization of
      Cryptosporidium parvum oocysts: quantitative interpretation.
AB  - Combined scattering and absorption properties of suspended particles can be
      obtained as a function of wavelength by measuring the complete ultraviolet
      visible (UV-vis) spectrum. This research reports on the quantitative
      interpretation of measured UV-vis spectra of Cryptosporidium parvum oocyst
      suspensions obtained from several commercial sources and evaluated using two
      different purification techniques. The reproducibility of the measured spectral
      data was assessed, and the quantitative interpretation of the oocyst spectra in
      terms of the particle size and the chemical composition of the particles are
      reported herein. The interpretation model of the spectra is based on light
      scattering theory, spectral deconvolution techniques, and on the approximation of
      the wavelength-dependent optical properties of the basic constituents of living
      organisms. A characteristic set of optical properties for C. parvum oocysts has
      been determined as a function of wavelength and used for the quantitative
      interpretation of UV-vis spectra. The results from the spectral deconvolution
      show quantitative differences among oocyst preparations. These results represent
      the first step in establishing a set of critical parameters (e.g., oocyst size
      and chemical composition) necessary for the detection and identification of C.
      parvum oocysts in water using spectroscopy.

PMID- 14655716
TI  - As, Hg, and Se flue gas sampling in a coal-fired power plant and their fate
      during coal combustion.
AB  - As, Hg, and Se are the most volatile elements in the flue gas from a coal-fired
      power plant. Significant amounts of these elements cause an undesired direct
      gaseous emission, which leads to a serious environmental health risk. The main
      focus of this study is to evaluate the possibility of simultaneous sampling of
      these volatile elements using an accurate official method for Hg (the most
      volatile element). A study of As, Hg, and Se emissions from a 1400 MW coal-fired
      power plant equipped with electrostatic precipitators (ESPs) was carried out for
      the combustion of a mixture of two types of coal. Simultaneous sampling of coal,
      bottom ash, fly ash, flue gas, and particles associated with the gas phase has
      been performed. Flue gas has been sampled by the Ontario Hydro Method Sampling
      Train, an ASTM method for Hg speciation. This sampling method was tested for As
      and Se sampling. As and Se determinations have been performed by HG-AAS, and Hg
      has been determined by CV-AAS. The results were used to examine the following:
      overall mass balances, relative distribution of these elements in the coal-fired
      power plant; As, Hg, and Se concentrations in coal and combustion residues; and
      predominant oxidation state for Hg in flue gas. The mass balances obtained for
      As, Hg, and Se were satisfactory in all cases; nevertheless, relative enrichment
      values in fly ash for As and Se were low; therefore, we concluded that As
      sampling in flue gas can be conducted by application of the Ontario Hydro Method;
      nevertheless Se released in the gas phase is not completely collected by this
      sampling train. Application of this sampling method allowed for performance of Hg
      speciation. The results indicated that Hg(II) was the predominant species in flue
      gas. It has also been proved that 24%, more than 99.8%, and 90% for As, Hg, and
      Se in the stack emissions, respectively, were in the gaseous phase.

PMID- 14655717
TI  - Comment on "Evaluation of the diffusive gradient in a thin film technique for
      monitoring trace metal concentrations in estaurine waters".

PMID- 14655718
TI  - Effects of Icon, a pyrethroid insecticide on early pregnancy of rats.
AB  - Icon is a water miscible type II synthetic pyrethroid insecticide based on active
      ingredient lambda cyhalothrin (10% w/w). It is used in Sri Lanka as an
      adulticidal indoor spray against malaria vector mosquitoes. The goal of this
      study was to assess the effects of Icon on pregnancy outcome of rats when exposed
      during early pregnancy (days 1-7). Icon was gavaged daily for 7 consecutive days
      in three different doses; 63, 83, or 125 mg/kg/day (active ingredient; lambda
      cyhalothrin; 6.3, 8.3, 12.5 mg/kg/day), respectively. Several parameters of
      reproduction and pre- and post-natal development were monitored. The results show
      that Icon is detrimental to pregnancy outcome (in terms of quantal pregnancy,
      number of uterine implants, implantation index and foetal deaths) but induced no
      detectable developmental defects. The anti-reproductive effects of Icon were
      mainly due to increased pre-implantation losses. Enhancement of post-implantation
      losses played a subsidiary role. These effects resulted from multiple mechanisms:
      maternal toxicity, stress, uterotropic activity and embryo-foetotoxicity. Further
      progesterone had a protective effect against Icon induced anti-reproductive
      actions. Overall, the results suggest that exposure to Icon during early
      gestation may result in a threat to pregnancy.

PMID- 14655719
TI  - Renal epithelial gene expression profile and bismuth-induced resistance against
      cisplatin nephrotoxicity.
AB  - Nephrotoxicity is the most important dose-limiting factor in cisplatin based anti
      neoplastic treatment. Pretreatment with bismuth salts, used as pharmaceuticals to
      treat gastric disorders, has been demonstrated to reduce cisplatin-induced renal
      cell death in clinical settings and during in vivo and in vitro animal
      experiments. To investigate the genomic basis of this renoprotective effect, we
      exposed NRK-52E cells, a cell line of rat proximal tubular epithelial origin, to
      33 microM Bi3+ for 12 hours, which made them resistant to cisplatin-induced
      apoptosis. Differentially expressed genes in treated and untreated NRK-52E cells
      were detected by subtraction PCR and microarray techniques. Genes found to be
      down regulated (0.17-0.31-times) were cytochrome c oxidase subunit I, BAR (an
      apoptosis regulator), heat-shock protein 70-like protein, and three proteins
      belonging to the translation machinery (ribosomal proteins S7 and L17, and S1, a
      member of the elongation factor 1-alpha family). The only up-regulated gene was
      glutathione S-transferase subunit 3A (1.89-times). Guided by the expression
      levels of these genes, it may be possible to improve renoprotective treatments
      during anti-neoplastic therapies.

PMID- 14655720
TI  - Evaluation of historical control data in carcinogenicity studies.
AB  - Results obtained in long-term carcinogenicity studies with animals should be
      evaluated, first and foremost, by statistical comparisons of the data obtained
      from the treated group with that from the concurrent control group. Often the
      results are compared with data from so-called historical control groups in order
      to take variations in the incidences of spontaneous tumours into account. Because
      historical control data change in the course of time and for a variety of
      reasons, certain requirements must be met before they may be used in the
      evaluation of the results of long-term studies. The present paper discusses
      potential sources of variability of tumour incidences in untreated animals,
      presents databanks for historical control data, mentions the factors that affect
      tumour incidences in untreated animals and describes biostatistical data
      evaluation. Finally, details are given of the criteria used by the DFG Commission
      for the Investigation of Health Hazards of Chemical Compounds in the Work Area to
      decide whether historical control data may be applied. These include the
      requirement that the historical control data were obtained with animals of the
      same species and strain and from the same breeder. The data were obtained in the
      same laboratory, the study design, experimental methods and assessment criteria
      were the same, and the studies used for the comparison were carried out within a
      limited time window. Historical control data that have not been published may be
      used provided they fulfil the above criteria and have been made available in
      sufficient detail to be comprehensible.

PMID- 14655721
TI  - Toxic effects of selenium inhalation: acute damage of the respiratory system of
      mice.
AB  - Accidental inhalation of selenium by humans has been associated with damage of
      respiratory tissues that is lacking a detailed histological definition. We have
      investigated the natural history of injury to the tracheal epithelium and lungs
      induced by a single intratracheal instillation of CD-1 mice with two different
      doses of dimethyl selenide (0.05 and 0.1 mg Se/kg of body weight). The animals
      were sacrificed 1, 7, 14, and 28 days after the single selenium treatment.
      Samples of the trachea and lungs were studied by light microscopy. The tracheal
      epithelium showed loss of cilia and acute necrosis that was followed by
      metaplastic transformation. Edema and diffuse alveolar damage was observed in the
      lungs. Our data suggest that: i) severity of respiratory lesions caused by
      selenium is dose dependent; ii) selenium causes transient metaplastic
      transformation of the tracheal epithelium; iii) chronic inflammation and
      increased thickness of alveolar septa occur in the lungs; iv) 4 weeks after
      selenium treatment, mice recover from the tracheal injury, whereas no
      amelioration of pulmonary lesions was observed.

PMID- 14655723
TI  - Yesterday, today, and tomorrow.

PMID- 14655722
TI  - Environmental lead exposure and its relationship to traffic density among
      Senegalese children: a pilot study.
AB  - In Senegal, as in many developing countries, traffic density is increasing in
      urban areas; in Dakar more than 50% of vehicles use gasoline. Yet the extent and
      real magnitude of the problem has neither been recognized nor assessed in these
      countries. Systemic data assessment of lead pollution and people's exposure are
      not well known in Senegal. This study was also designed to determine the
      impregnation levels of the lead released by the exhaust of cars and the changes
      of some early biological markers in Senegalese children. Blood lead (BPb) levels
      showed that all the children enrolled were exposed. However, lead exposure levels
      (from 34.7 to 145.8 microg/L) were less important for children living in rural
      areas (60.9+/-18.3 microg/L) than for those living in urban areas (106.7+/-16.9
      microg/L). These changes could be correlated to the difference in the automobile
      traffic between both these regions (P < 0.001). BPb mean levels found in boys
      were higher than those in girls (P < 0.05). Despite elevated BPb levels, all
      values for blood zinc protoporphyrin and urine delta-aminolevulinic acid were
      within physiological ranges. In addition, variations in some biological markers
      of oxidative stress and renal disorders were seen; however, they must be
      confirmed by a future epidemiological study.

PMID- 14655724
TI  - Extracorporeal liver support: waiting for the deciding vote.
AB  - Because acute liver cell failure is associated with an exceedingly high
      mortality, liver support has been proposed since the 1950s to improve patient
      outcome. Early devices, including hemodialysis, hemofiltration, exchange
      transfusion, plasmapheresis, hemoperfusion, plasma and cross-hemodialysis or
      cross-circulation, appeared inefficient. Meanwhile, documented results of
      extracorporeal liver perfusion (ECLP) suggested its superiority over conventional
      treatment. These devices were abandoned with the development of liver
      transplantation (LT), which allowed a better outcome and longer survival rate. In
      the present day, the fact that patients die while waiting for LT because of organ
      shortage led to a renewed interest in liver support as bridge to LT or
      regeneration. These devices can be classified according to the presence or lack
      of hepatocytes, whereas biologic devices refers to the presence of cells or other
      organic and biochemical component. The absence of individual success of early
      models led to the development of combined hepatocyte free devices, or artificial
      liver, which are based upon the hemodiabsorption principle (Biologic-DT) or on
      the "albumin bound toxin hypothesis" (Molecular Adsorbents Recirculating System)
      with encouraging results. Meanwhile, hepatocyte based bioartificial liver devices
      (BLD) were conceived for a global "metabolic support." BLD were developed with
      the use of human hepatoma cell line (C3A) or primary or cryopreserved porcine
      hepatocytes. Preliminary experience gave promising results bridging patients to
      LT. Based upon the same principle of global hepatocyte metabolic support, ECLP
      regained interest, particularly with the development of transgenic pigs. Several
      concerns were raised about these devices. Artificial livers lacked any metabolic
      synthetic activity, the use of human liver for ECLP seems hardly acceptable
      because of organ shortage, and the accepted use of borderline livers for
      transplantation is pending trials for the use of xenogenic livers. For BLD, the
      concerns were the low hepatocyte mass, the absence of accessory liver cells, and
      the potential risk of seeding tumor cells into patient with the use of human
      hepatoma cell line. The use of porcine hepatocytes (BLD or ECLP) raised
      physiologic and immunologic concerns and particularly the fear of a possible
      transfer of porcine viral material. Although recent studies clearly demonstrate
      clinical improvement of patients with the use of recently developed liver support
      devices, most of reported prospective, controlled, or randomized trials had a
      small number of patients. To give the deciding vote and avoid previous pitfalls,
      trials need to be developed with a larger number of patients based upon
      statistically significant models with the following characteristics: 1)
      comprehensive understanding of the acute liver cell failure mechanisms, 2) world
      wide classification of conditions that require liver support, and 3) a clear
      definition of treatment success pending patients to LT or recovery without
      transplantation. There has not yet been conclusive evidence to support the
      benefits of extracorporeal liver support. We are still waiting for the deciding
      vote.

PMID- 14655725
TI  - The birth of our logo.

PMID- 14655726
TI  - Lentiviral vector: a useful tool for transduction of human liver endothelial
      cells.
AB  - Endothelial cells play multiple roles in pathophysiologic processes and are
      increasingly being recognized as target cells of gene therapy. Lentiviral vectors
      derived from human immunodeficiency virus type 1 have an ability to infect both
      dividing and nondividing cells and currently receive a great deal of attention as
      an innovative tool for transduction of target cells. The purpose of the present
      work was to evaluate the efficacy of a lentiviral vector for transducing human
      liver endothelial cells (HLECs) in vitro. For the present study, a pseudotyped
      lentiviral vector encoding a green fluorescent protein (GFP) gene, LtV-GFP, was
      generated by means of FuGENE 6 method and allowed to infect HLECs. Approximately
      95% of HLECs were positive for GFP expression after LtV-GFP infection at a
      multiplicity of infection of 10. Notably, LtV-GFP transduced HLECs had stable and
      long term GFP expression, showed gene expression of endothelial markers including
      CD 34, factor VIII, flt-1, KDR/flk-1 and HGF, and maintained in vitro angiogenic
      potential in a Matrigel assay to the same extent as primarily cultured HLECs.
      These findings provide evidence that lentivirus based gene delivery is an
      efficient tool for transduction of endothelial cells that could be considered for
      cell and gene therapies and hybrid artificial organs.

PMID- 14655727
TI  - Nonviral gene gun mediated transfer into the beating heart.
AB  - Several techniques for gene transfer into the heart have been developed,
      including direct injection of naked plasmid DNA into the myocardium and coronary
      infusion of various viral vectors. However, complications and side effects with
      those methods have been reported. In this study, to resolve these problems, the
      authors investigated the feasibility of nonviral gene transfer into the beating
      heart with the hand held gene gun. The genes pCAGGS/CTLA4-EGFP were coated around
      the surface of gold particles. Three sizes of gold particles (0.6, 1.0, and 1.6
      microm in diameter) and three settings of helium gas pressure (200, 250, and 300
      psi) were examined. Gene transfer into the rat beating heart was performed using
      the hand held gene gun. EGFP expressions were detected by fluorescence microscopy
      from day 1 to 3 weeks after bombardment. The most prominent expressions were
      detected with the combination of 1.0 microm gold particles and 300 psi helium gas
      pressure. In this study, the present authors showed that non-viral gene transfer
      into the beating heart was feasible with the hand held gene gun. This technique
      is effective for gene transfer into the heart and may be one of the most useful
      methods for gene therapy for many cardiovascular diseases in the future.

PMID- 14655728
TI  - Blood access and daily hemodialysis: clinical experience and review of the
      literature.
AB  - The present authors studied longevity and complications with fistulae, grafts,
      and central venous catheters in 23 patients on daily hemodialysis for a total of
      409 patient months (mean 18 +/- 10 months) and 9,209 dialyses. Fourteen patients
      had fistulae, five had grafts, and four had catheters. These required one, one,
      and two replacements respectively during a total observation time of 254, 105,
      and 50 patient months. Fistulae required 0.05 replacements per year vs. 0.11
      replacements per year for grafts and 0.48 replacements per year for catheters (p
      = 0.042, fistulae vs. other accesses). Cumulative survival at 15 months was 100%
      for fistulae, 80% for grafts, and 20% for catheters, and at 3 years it was 80%
      for fistulae and grafts. No catheter survived beyond 15 months (p = 0.041).
      Twenty-seven events required hospitalization or an outpatient intervention.
      Fistulae had 0.52 events per patient year, grafts 1.37 events per patient year,
      and catheters 1.44 events per patient year (p = 0.080, fistulae vs. other
      accesses). Patients with fistulae reported more problems between dialyses, these
      occurring on 3.2% of the observation days compared with 0.2% for grafts and 0.4%
      for catheters (p < 0.0001). Eighty-five percent of these problems were pain and
      redness at the access site. During dialysis, there were more problems with
      catheters (9.1% vs. fistulae 2.7% and grafts 0.9%, p < 0.0001). Complications and
      survival data were similar to those reported with daily hemodialysis by others
      and better than data from reports of access problems with conventional three
      times weekly hemodialysis. In conclusion, daily hemodialysis does not adversely
      affect the usual types of blood access. Survival was best and need for
      intervention was least with fistulae and worst with catheters. Grafts, when
      functioning, had fewer problems both between and during dialyses.

PMID- 14655729
TI  - Coronary bypass grafting for patients dependent on dialysis: modified
      ultrafiltration for perioperative management.
AB  - Coronary bypass grafting for patients on chronic dialysis has increased the risk
      of operative mortality, and long-term survival is considered poor. Thirty-three
      patients dependent on dialysis undergoing coronary bypass grafting were analyzed.
      The 33 patients were divided into two groups according to the strategy for renal
      support. In group A, 12 patients underwent continuous hemofiltration (CHF) during
      and after cardiopulmonary bypass and CHF in an intensive care unit (ICU) and then
      returned to regular dialysis. In group B, 21 patients underwent modified
      ultrafiltration (UF) immediately after cardiopulmonary bypass and continuous
      hemodialysis and filtration in an ICU with early reinstitution of regular
      dialysis. Two patients died in group A, and there were no operative deaths in
      group B (17% vs. 0%, p < 0.05). Three patients in group A and one patient in
      group B had bleeding complications requiring reoperation (25% vs. 5%, p < 0.05).
      Three patients in group A and one patient in group B needed intraaortic balloon
      pump (IABP) support postoperatively (25% vs. 5%, p < 0.05). Four patients in
      group A and one in group B required long-term ventilation of more than 3 days
      (33% vs. 5%, p < 0.05). There were five patients in group A and two patients in
      group B requiring long-term ICU stay of more than 4 days (41% vs. 10%, p < 0.05).
      Postoperative blood loss within 24 hours was 1310 ml in group A and 623 ml in
      group B (p < 0.05). Transfusion requirements were 9.3 units in group A and 3.0
      units in group B (p < 0.05). During follow-up, the long-term survival, New York
      Heart Association (NYHA) functional class, and incidence of recurrent angina were
      considered favorable in both groups. Cardiac event-free rates after surgery at 1,
      3, and 5 years were 88%, 73%, and 67%, respectively. The operative mortality,
      morbidity, and long-term survival for dialysis dependent patients were reasonably
      acceptable. As renal support, modified UF can play an important role in reducing
      bleeding complications, shortening the ICU stay, and decreasing blood loss and
      transfusion requirements.

PMID- 14655730
TI  - Effect of incremental doses of folate on homocysteine and metabolically related
      vitamin concentrations in nondiabetic patients on peritoneal dialysis.
AB  - The role of folate supplementation in reducing hyperhomocystinemia in patients on
      dialysis has been reported, but the optimal dose of folate is still unknown. The
      aim of the present study was to investigate whether greater than 5 mg/day folate
      supplementation provides any additional effect on plasma homocysteine (HCY)
      levels. The study was prospective, open, and had no control group. Of the 64
      eligible nondiabetic patients on peritoneal dialysis with hyperhomocystinemia
      (>20 micromol/L), 56 were given oral folate (5 mg/day) for 3 months. When Hcy did
      not fall below 20 micromol/L, folate doses were increased by 5 mg every 3 months
      to up to 15 mg/day. With 5 mg/day supplementation, serum folate concentrations
      increased above the upper confidence limit in 23 patients and erythrocyte folate
      concentrations in 27 patients. Hcy levels decreased to less than 15 micromol/L in
      6 cases and by more than 50% in 12 cases. Nineteen of the remaining patients were
      given 10 mg/day folate. After increasing the dose, serum and erythrocyte folate
      levels rose above the upper detection limit. In one patient, plasma Hcy
      concentrations decreased to less than 15 micromol/L. Ten patients were given 15
      mg/day oral folate for an additional 3 months with no effect on homocystinemia.
      This study confirms that oral folate supplementation may improve
      hyperhomocystinemia even in patients on dialysis with normal serum or erythrocyte
      folate concentrations. In fact, serum and erythrocyte levels cannot predict the
      effect of supplementation on plasma Hcy levels. However, 5 mg/day folate
      supplementation normalized Hcy in 10% of cases and reduced Hcy levels in another
      21%. Increasing the folate dose to greater than 5 mg/day had a minimal (10
      mg/day) or no (15 mg/day) additional effect on Hcy concentrations. Despite the
      minimal effect of increasing folate doses, given the low cost, the absence of
      side effects, and the high cardiovascular risk for patients on peritoneal
      dialysis, a careful attempt to increase the dose of oral folate up to 10 mg/day
      might be suggested.

PMID- 14655731
TI  - Serum potassium handling at pre- and posthemodialysis in patients with end-stage
      renal disease.
AB  - The current study simultaneously measured serum and red blood cell (RBC) K+ as
      well as plasma pH, bicarbonate, serum insulin, and aldosterone at pre-, end-, and
      at 5, 11, and 19 hours posthemodialysis in 25 patients with end-stage renal
      disease and evaluated the factors influencing serum K+ levels during those
      periods. Our patients were studied under their current dietary conditions. At end
      dialysis, serum K+ levels decreased, but RBC K+ levels were not changed. At this
      time point, the decrease in serum K+ levels was exclusively caused by removal of
      K+ by dialysis. At 5 hours postdialysis, serum K+ rapidly increased, whereas RBC
      K+ decreased. The 5 hour postdialysis serum K+ increase negatively correlated
      with the decrease in serum insulin levels. At 11 hours postdialysis, serum K+
      slowly but significantly increased, and RBC K+ increased to those levels at pre-
      and end-dialysis. At 19 hours postdialysis, serum K+ further increased, but RBC
      K+ remained stable. From 5 to 19 hours postdialysis, the increase in serum K+ was
      independent of changes in plasma pH, bicarbonate, insulin, and aldosterone but
      was associated with both the predialysis serum K+ levels and the magnitude of the
      decrease in serum K+ at end-dialysis.

PMID- 14655732
TI  - Evaluation of the harmonized alert sensing technology device for hemodynamic
      monitoring in chronic hemodialysis patients.
AB  - The Harmonized Alert Sensing Technology (HASTE) device was developed to overcome
      the primary shortcomings of interval based noninvasive blood pressure (BP)
      monitoring. This study was conducted to assess the reliability of the HASTE
      system compared with standard cuff BP values in patients on hemodialysis. A total
      of 1,370 HASTE measurements were compared with oscillometric standard cuff
      systolic BP values in 42 sessions of 15 patients on hemodialysis. The average
      discrepancy between the HASTE and cuff systolic BP was 1.41 +/- 16.90 mm Hg.
      Compared with cuff measurements, 31% of systolic BP fell within a range of 5 mm
      Hg difference, 57% of systolic BP fell within 10 mm Hg, and 73% of systolic BP
      fell within a 15 mm Hg band. According to British Hypertension Society standards
      or Association for the Advancement of Medical Instrumentation criteria, the
      current HASTE method did not perform well. Technology to provide noninvasive
      hemodynamic monitoring is, however, in its developmental stage. The effort at
      continuous systolic pressure monitoring using existing, readily available, and
      frequently used techniques is exciting. Although the HASTE system as currently
      configured and calibrated did not adequately perform, variations in site analysis
      and conversion factors may increase pressure sensitivity and tracking over the
      course of a standard dialysis treatment.

PMID- 14655733
TI  - Short term performance evaluation of a perfluorocopolymer coated gas exchanger
      for arteriovenous CO2 removal.
AB  - A new perfluorocopolymer coating for micropore hollow fiber gas exchangers was
      developed to improve gas exchange, reduce plasma leakage, and reduce blood
      surface interactions. The present authors evaluated gas exchanger performance
      using this new coating in a prospective, randomized, controlled, unblinded, large
      animal model of CO2 retention. Adult sheep (30-40 kg), under general anesthesia,
      underwent cannulation of the carotid artery (12 F) and jugular vein (14 F). The
      perfluorocopolymer coated (n = 5) and uncoated (n = 5) gas exchangers were
      attached to an arteriovenous CO2 removal (AVCO2R) circuit. Blood gases, CO2
      removal, and hemodynamics were monitored throughout the 6 hour study. Average CO2
      removal was 107.6 +/- 15.6 ml/min (coated) vs. 93.0 +/- 13.9 ml/min (uncoated; p
      < 0.01). PaCO2 and CO2 removal for both coated and uncoated did not deteriorate
      significantly over the study. Average AVCO2R blood flow was 1,130 +/- 25 ml/min
      (coated) versus 1,101 +/- 79 ml/min (uncoated; p = not significant). Likewise,
      cardiac output and AVCO2R blood flow did not change over the duration of the
      study. No significant differences in the pressure gradient or resistance between
      devices (coated, 6.89 +/- 1.14 mm Hg/L/min; uncoated, 6.42 +/- 0.23 mm Hg/L/min)
      was noted. The authors concluded that the new perfluorocopolymer coated gas
      exchanger improved CO2 removal without compromising hemodynamics in an acute
      performance evaluation.

PMID- 14655734
TI  - Blood flow pulsatility effects upon oxygen transfer in artificial lungs.
AB  - This report discusses theoretical effects of blood flow pulsatility upon the rate
      of oxygen transfer in artificial lungs, demonstrates the effects with in vitro
      tests upon commercial oxygenators, and applies the theory to these oxygenators
      and to a thoracic artificial lung. Steady flow gas transfer theory is applied to
      pulsatile flow by using the instantaneous value of flow rate at each instant of
      time, that is, quasi-steady gas transfer. The theory suggests that the local rate
      of oxygen transfer for a given device and blood composition is proportional to
      the flow rate to a power less than unity and to the hemoglobin saturation level.
      It predicts, for some cases, overall reduced rates of gas transfer for pulsatile
      flow relative to those at steady flow for the same mean blood flow rates. In
      vitro bovine blood tests, using pediatric oxygenators, a pulsatile pump, and an
      adjustable compliance chamber, indicate a significant average 10% reduction of
      oxygen transfer for pulsatile flow relative to steady flow. The application of
      the theory to the oxygenators predicts gas transfer values that are in agreement
      with those measured during the experiments. The results have implications in the
      design of implantable thoracic artificial lungs, which should include a compliant
      section to dampen the cardiac pulse. A relatively small compliance (0.2 ml/mm Hg)
      at the thoracic artificial lung inlet is sufficient to obtain approximately 95%
      of steady flow oxygen transfer.

PMID- 14655735
TI  - Short exposure time sensitivity of white cells to shear stress.
AB  - White cells are a critical functional element circulating in blood. This study
      sheared fresh whole bovine blood in stainless steel and polymeric capillary tubes
      of various lengths and diameters. Flow rate was constant, resulting in a range of
      exposure times and shear stresses. White cell count, cell integrity (trypan blue
      exclusion), and phagocytic index (latex bead ingestion) were assayed. It was
      found that cell function declined at lower stresses than cell count. White cell
      count was maintained at higher stress levels at the short exposure times used
      here compared with the published results at longer times. This study suggests
      that function, not count, is the critical parameter when studying shear effects
      on white cells, and that, like red cells, there may be an exposure time effect
      and that white cell function is impacted at stresses lower than are required for
      hemolysis.

PMID- 14655736
TI  - A new method to evaluate the local clearance at different annular rings inside
      hemodialyzers.
AB  - Recent research indicated that the dialysate flow distribution inside a
      hemodialyzer was not uniform ("channeling" of the dialysate flows). However,
      effect of the channeling on the solute clearance has not been directly and
      quantitatively examined. In this report, a novel experiment approach is presented
      to test the hypothesis that hollow fibers in different regions within a given
      hemodialyzer may contribute differently to the solute clearance. Water solution
      with urea (molecular weight 60) and creatinine (molecular weight 113) were made
      as "blood," and pure water was used as dialysate. Two high flux dialyzers,
      dialyzer A (cellulose triacetate) and dialyzer B (polyethersulfone), were used in
      this study. The hollow fiber potting area at the blood inlet of a dialyzer was
      divided into equal area concentric rings. In each experiment, only one of the
      rings was open for blood flow, and the other rings were blocked by epoxy. The
      "blood" was pumped at 120 ml/min while the dialysate flow rate (Qd) varied at
      500, 800, and 1,000 ml/min, respectively. The solute clearance with a specific
      ring open (local clearance) was determined by measuring solute (urea/creatinine)
      concentration at the "blood" inlet and outlet. For dialyzer A, local clearance of
      urea and creatinine were significantly higher in the outer ring than in the inner
      ring. With increasing Qd, local solute clearance increased significantly for all
      rings. For dialyzer B, at any given Qd, solutes local clearance also increased
      from the inner to outer rings. In comparison, the effect of increasing Qd on
      solute clearance was greater for dialyzer B than for dialyzer A. In conclusion,
      using the new experimental method, the authors quantitatively evaluated the
      solute clearance contributed by the hollow fibers at different locations
      (concentric rings) in dialyzers. Hollow fibers at different locations did
      contribute differently to the solute clearance, which may be caused by the
      channeling of dialysate flow. A careful design of the dialyzer to minimize the
      channeling is needed.

PMID- 14655737
TI  - Recording vagal nerve activity for the control of an artificial heart system.
AB  - Monitoring cardiovascular control system information is important in considering
      the quality of life (QOL) of patients with artificial hearts. Natural heart
      circulation is controlled by an autonomic nervous system. Therefore, it is
      desirable to record autonomic nerve activity for the control of artificial heart
      systems. We directly recorded vagal nerve activity in long-term animal
      experiments. Six healthy adult goats were anesthetized with halothane inhalation,
      and thoracotomy was performed with the fourth rib resection during mechanical
      ventilation. Arterial blood pressure and right and left atrial pressures were
      continuously monitored with an inserted catheter. Cardiac output was measured by
      an electromagnetic flow meter attached to the ascending aorta. After the chest
      was closed, an incision was made in the left neck, and the left vagal nerve was
      separated. Stainless steel electrodes were inserted into the vagal nerve and
      fixed by a plasticizer. After the incision was closed, the goats were transferred
      to a cage and extubated after waking. Vagal nerve activity was measured using
      hemodynamic parameters when the animals were awake. Our results show that clear
      observation of autonomic nerve discharge was made through this experimental
      system for over 1 month. The tonus of the vagal nerve was significantly altered
      before body motion with hemodynamic changes, suggesting the possibility of
      prediction. These results suggest that information from autonomic nerves may help
      to control implantable artificial hearts or ventricular assist devices.

PMID- 14655738
TI  - Investigating the functionality of diamond-like carbon films on an artificial
      heart diaphragm.
AB  - In this study, the authors used diamond-like carbon film to coat the ellipsoidal
      diaphragm (polyurethane elastomer) of artificial hearts. The purpose of such
      coatings is to prevent the penetration of hydraulic silicone oil and blood
      through the diaphragm. To attach diamond-like carbon film uniformly on the
      diaphragm, the authors developed a special electrode. In estimating the
      uniformity of the diamond-like carbon film, the thickness was measured using a
      scanning electron microscope, and the characteristics of the diamond-like carbon
      film was investigated using infrared spectroscopy, Ar-laser Raman
      spectrophotometer, and x-ray photoelectron spectrometer. Also, to estimate the
      penetration of silicone oil through the diaphragm, in vitro testing was operated
      by alternating the pressure of silicone oil for 20 days. The authors were able to
      successfully attach uniform deposition of diamond-like carbon film on the
      ellipsoidal diaphragm. In this in vitro test, diamond-like carbon film was proven
      to have good stability. The amount of silicone oil penetration was improved by
      one-third using the diamond-like carbon film coating compared with an uncoated
      diaphragm. It is expected that through the use of the diamond-like carbon film,
      the dynamic compatibility of an artificial heart diaphragm will increase.

PMID- 14655739
TI  - Prolonged catheter survival in intermittent hemodialysis using a less
      thrombogenic micropatterned polymer modification.
AB  - Adequate vascular access is a major prerequisite for hemodialysis treatment.
      Catheter related complications, in particular thrombus formation, are frequent,
      difficult to handle, and cost intensive. We investigated whether a new surface
      modified catheter containing a microdomain structure is beneficial for catheter
      survival. Surface thrombogenicity of standard double lumen catheters (STD-DC) and
      surface modified film-coated domain structured double lumen catheters (FCDS-DC)
      consisting of a novel reactive polyurethane copolymer coating was assessed by
      measurement of thrombinantithrombin (TAT) III complex in vitro. Furthermore, in a
      randomized observational study with 20 patients on hemodialysis, we analyzed
      catheter survival of either STD-DC (GamCath GDK 11 French, length 12.5 or 15 cm)
      or FCDS-DC (GamCath Dolphin GDK 11 French, length 12.5 or 15 cm). Catheter care
      protocol was identical, and dialysis treatment parameters were kept constant in
      both groups. In vitro measured surface thrombogenicity was reduced in the
      modified catheter compared with standard catheter. The clinical investigation
      revealed that both number of days before catheter removal according to clinical
      requirements and number of treatments per catheter were significantly higher with
      the modified catheter as compared with the standard catheter (14.5 vs. 10.3 days;
      7 vs. 4 treatments; p < 0.03, Fisher-Yates test). Micropatterned surface coating
      with a polyurethane polymer significantly increased catheter survival and the
      number of treatments per catheter.

PMID- 14655740
TI  - Overspill of catheter locking solution: safety and efficacy aspects.
AB  - Avoidance of clotting in catheter lumens between treatments usually entails
      locking with an anticoagulant solution such as heparin. Catheter manufacturers
      specify internal volume of the catheters, and it is commonly assumed that
      injection of this precise filling volume is safe and efficient. However, it has
      been shown that activated partial thromboplastin time (aPTT) increases after
      instillation of the heparin lock volume specified by the manufacturer. We have
      investigated this phenomenon in vitro using dye and saline dilution and found
      that injection of the catheter volume results in spillage of up to 15% of the
      catheter volume into the patient's blood. Depending on fluid dynamics of the
      instillation process and catheter compliance, the concentration of the locking
      solution at the catheter tip is much reduced. As a consequence of this overshoot,
      the mean concentration at the tip is reduced to approximately 90%. In conclusion,
      the injection volume must exceed 120% of the catheter lumen for achieving the
      full strength of the locking solution at the tip. The overshoot may have clinical
      consequences, (e.g., bleeding if highly concentrated heparin is used).

PMID- 14655741
TI  - Aqueous oxygen attenuation of reperfusion microvascular ischemia in a canine
      model of myocardial infarction.
AB  - Uncorrected microvascular ischemia may contribute to left ventricular impairment
      during reperfusion after prolonged coronary artery occlusion. Attenuation of such
      ischemia in microvessels with impaired erythrocyte flow may require delivery of
      oxygen at high levels in plasma. Intraarterial infusion of aqueous oxygen (AO)
      can be used in a site specific manner to achieve hyperoxemic levels of
      oxygenation in the perfusate. With this new approach, the hypothesis was tested
      that reperfusion microvascular ischemia can be attenuated. After a 90 min
      coronary balloon occlusion in a canine model, AO hyperoxemic intracoronary
      perfusion was performed for 90 min after a 30 min period of autoreperfusion.
      Control groups consisted of normoxemic reperfusion, both passive
      (autoreperfusion) and active (roller pump). A significant improvement in left
      ventricular ejection fraction (p < 0.05) at 2 hr of reperfusion was noted only in
      the AO hyperoxemia group (17 +/- 6% by two dimensional echo), without a
      significant reduction in the improvement 1 hr after termination of treatment.
      During AO hyperoxemic perfusion, ECG ST segment isoelectric deviation normalized,
      and frequency of ventricular premature contractions was significantly reduced, in
      contrast to the autoreperfusion control group (p < 0.05). Microvascular blood
      flow, measured as the ischemic/normal left ventricular segment ratio by
      radiolabeled microspheres immediately after AO hyperoxemic perfusion, was double
      the value of the autoreperfusion control group at 2 hr of reperfusion (p < 0.05).
      We conclude that reperfusion microvascular ischemia is attenuated by
      intracoronary AO hyperoxemic perfusion and acutely improves left ventricular
      function in this model.

PMID- 14655742
TI  - Prolonged controlled hemorrhagic shock in a swine model: is there a role for
      mechanical circulatory assistance?
AB  - Outcomes of mechanical circulatory assistance during hemorrhagic shock were
      evaluated in a swine model. Pigs were bled to a mean arterial pressure of 35 mm
      Hg (group I, n = 3) or 40 mm Hg (group II, n = 5; group III, n = 5), maintained
      there for 30 minutes, and then resuscitated with fluids alone (groups I and II)
      or fluids plus mechanical circulatory assistance (group III). Mean blood loss was
      greater in group I than in groups II or III (1,037 +/- 212 vs. 862 +/- 387 ml vs.
      681 +/- 117 ml, respectively; I vs. III, p < 0.05) and survival was shorter (230
      +/- 25.5 min vs. 709 +/- 251 min vs. 662 +/- 428 min, respectively; I vs. II or
      III, p < 0.05). Cardiac arrhythmia caused death in most cases. Mean biochemical
      parameters increased progressively in all cases. Left anterior descending
      coronary artery flow stayed relatively constant in group II but increased in
      group III. Superior mesenteric artery flow returned to baseline in group II but
      increased in group III. Cardiac output was similar in groups II and III, but SGOT
      levels significantly differed (750 +/- 135 U/L vs. 359 +/- 157 U/L; p < 0.005).
      These results suggest that the swine model will be useful for studying ways to
      improve outcomes after prolonged hemorrhagic shock.

PMID- 14655743
TI  - Thoratec ventricular assist devices in children with less than 1.3 m2 of body
      surface area.
AB  - This report summarizes the multicenter experience with the Thoratec paracorporeal
      pneumatic ventricular assist device (VAD) (Thoratec Corp., Pleasanton, CA) in
      small children. Between October 1988 and August 2001, 19 children (11 male, 8
      female) with less than 1.3 (mean 1.09, range 0.73-1.29) m2 body surface area
      (BSA) have been supported with univentricular (9) or biventricular (10) Thoratec
      VADs in 12 centers in the United States and Germany. Mean patient age was 10
      (range 7-14) years, mean weight 31 (range 17-41) kg. Indications for support were
      end-stage cardiomyopathy in eight patients, myocarditis in three, end-stage
      congenital heart disease in seven, and transplant graft failure in one patient.
      Mean duration of support was 43 (range 0-120) days. In patients with
      cardiomyopathies and myocarditis, survival through discharge occurred in 8 of 11
      (72%) patients; however, only 1 of 7 patients with congenital disease survived.
      Outcome appeared independent of patient size. Neurologic complications were
      significant and predominant in the congenital disease group. Our experience
      suggests that the Thoratec VAD can be successfully used in these difficult
      patients, particularly in children with cardiomyopathies and myocarditis.
      Congenital disease is associated with increased risk. To reduce thromboembolic
      risk, we recommend left ventricular as opposed to left atrial inflow cannulation
      and higher device rates with partial stroke volumes.

PMID- 14655744
TI  - Hemodynamic effects of a new percutaneous circulatory support device in a left
      ventricular failure model.
AB  - We have tested a new percutaneous circulatory support device in seven
      anesthetized calves with induced left ventricular failure. The device is based on
      a flexible catheter with a foldable propeller and cage at the distal end. The
      rotation of the propeller (1,000-15,000 rpm) is transmitted from a drive unit at
      the proximal end to the propeller by way of a rotating wire inside the catheter.
      This also contains an umbrella-like mechanism to open the pump head from the
      folded (diameter 4.6 mm) to the active position. The rotation of the propeller
      creates a pressure drop in front of the propeller and a pressure rise behind.
      Heart failure was induced with metoprolol and verapamil in combination with a VVI
      pacemaker to create a left atrial pressure greater than 20 mm Hg. A centrifugal
      pump was used to bypass the right ventricle and to ensure a sufficient filling of
      the left ventricle. After baseline recordings, the pump was run at 14,000 rpm,
      and the hemodynamic response was compared with the baseline. A 24 +/- 10 mm Hg
      pressure gradient was generated across the pump, resulting in a drop in the right
      carotid artery mean pressure from 80 +/- 11 to 71 +/- 13 mm Hg (p = 0.008) and a
      drop in the left ventricular systolic pressure from 109 +/- 17 to 100 +/- 19 mm
      Hg (p = 0.004). The pressure in the left atrium decreased from 25 +/- 3 to 20 +/-
      5 mm Hg (p = 0.008). The mean femoral pressure increased from 78 +/- 10 to 95 +/-
      20 mm Hg (p = 0.005). A moderate reduction in the right carotid flow was observed
      (15%, p = 0.029), whereas no significant changes were found in the coronary flow,
      the flow in the right femoral artery, or in the left kidney. The device showed a
      significant unloading of the left ventricle and an increased perfusion pressure
      for the lower part of the body. The moderate changes in flow were probably caused
      by still active autoregulation, and this needs to be tested with more pronounced
      circulatory failure.

PMID- 14655745
TI  - Testing of a centrifugal blood pump with a high efficiency hybrid magnetic
      bearing.
AB  - The purpose of this article is to present test results for a second generation,
      high efficiency, nonpulsatile centrifugal blood pump that is being developed for
      use as a left ventricular assist device (LVAD). The LVAD pump uses a hybrid
      passive-active magnetic bearing support system that exhibits extremely low power
      loss, low vibration, and high reliability under transient conditions and varying
      pump orientations. A unique feature of the second generation design configuration
      is the very simple and direct flow path for both main and washing blood flows.
      The pump was tested in both vertical and horizontal orientations using a standard
      flow loop to demonstrate the performance and durability of the second generation
      LVAD. Steady state and transient orientation pump operating characteristics
      including pressure, flow, speed, temperatures, vibration, and rotor orientation
      were measured. During the tests, pump performance was mapped at several operating
      conditions including points above and below the nominal design of 5 L/min at 100
      mm Hg pressure rise. Flow rates from 2 to 7 L/min and pressure rises from 50 to
      150 mm Hg were measured. Pump speeds were varied during these tests from 2,500 to
      3,500 rpm. The nominal design flow of 5 L/min at 100 mm Hg pressure rise was
      successfully achieved at the design speed of 3,000 rpm. After LVAD performance
      testing, both 28 day continuous duty and 5 day transient orientation durability
      tests were completed without incident. A hydrodynamic backup bearing design
      feasibility study was also conducted. Results from this design study indicate
      that an integral hydrodynamic backup bearing may be readily incorporated into the
      second generation LVAD and other magnetically levitated pump rotors.

PMID- 14655746
TI  - Evaluation of floating impeller phenomena in a gyro centrifugal pump.
AB  - The Gyro centrifugal pump, developed as a totally implantable artificial heart,
      was designed with a free impeller in which the rotational shaft (male bearing) of
      the impeller was completely separated from the female bearing. For this type of
      pump, it is very important to keep the proper magnet balance (impeller-magnet and
      actuator-magnet balance) to prevent thrombus formation or bearing wear. When the
      magnet balance is not proper, the impeller is jerked down into the bottom
      bearing. On the other hand, if magnet balance is proper, the impeller is lifted
      off the bottom of the pump housing within a certain range of pumping conditions.
      In this study, this floating phenomenon was investigated in detail. The floating
      phenomenon was proven by observation of the impeller behavior by means of a
      transparent acrylic pump. The impeller floating phenomenon was mapped on a pump
      performance curve. The impeller floating phenomenon is affected by the magnet
      magnet coupling distance and the rotational speed of the impeller. To keep the
      proper magnet balance and to maintain the impeller floating phenomenon at the
      driving conditions of right and left pumps, the magnet-magnet coupling distance
      was altered by a spacer that was installed between the pump and actuator. It
      became clear that the same pump could handle different conditions (right and left
      ventricular assist) by changing the thickness of the spacer. When magnet balance
      is proper, the floating impeller phenomenon occurs automatically in response to
      the impeller revolution. This is called "the dynamic revolutions per minute
      suspension."

PMID- 14655747
TI  - Device related infections while on left ventricular assist device support do not
      adversely impact bridging to transplant or posttransplant survival.
AB  - We conducted a retrospective review of our bridge to transplant experience over
      the last 7 years using the Heartmate device (Thoratec, Pleasanton, CA) by
      studying patients who developed device related infections. Of the 174 patients
      who underwent device implantation, 32 (18.4%) developed a device related
      infection while on support (12 patients with drive line infections, 14 patients
      with pocket infections, 4 patients with pump infections, and 2 patients with
      device endocarditis). There was no significant difference in rate of successful
      bridging to transplant between patients with and without a device related
      infection occurring in 23 (71.9%) patients with infection and 103 (72.5%)
      patients without infection (p = 0.406). In addition, posttransplant survival at
      1, 3, and 5 years was similar for both groups--95.6%, 86.2%, and 79.3%,
      respectively, for patients with infection, versus 90.9%, 88.1%, and 82.2%,
      respectively, for patients without infection (p = 0.911).

PMID- 14655748
TI  - Hemodialysis catheter tip embolization in the right pulmonary vasculature: report
      of a cardiac arrest.
AB  - A 44 year old woman on hemodialysis presented a sudden cardiorespiratory arrest
      at the end of an otherwise uneventful dialysis session. It occurred while
      disconnecting the circuit from her tunneled catheter. She was reanimated and then
      transferred to the intensive care unit; the endotracheal intubation had been
      difficult, and she had been severely hypoxic. It was noted that the external
      venous clamp of the tunneled catheter was broken and the hypothesis of a break
      during the reanimation process was entertained. The routine chest x-ray
      postintubation showed that the tip of the catheter was ruptured and visible in
      one branch of the right pulmonary artery. The catheter was changed over a guide
      wire, and the broken catheter was sent for analysis to the manufacturer. A
      selective angiography of the right pulmonary artery was performed with the
      purpose of removing the fractured catheter tip but was unsuccessful. The patient
      recovered neurologic function slowly over the next 4 months. The exact etiology
      of the arrest remains incompletely understood; it is unknown whether it was
      caused by the catheter tip embolization or if an air embolism occurred.

PMID- 14655749
TI  - Frequent LOH at chromosome 12q22-23 and Apaf-1 inactivation in glioblastoma.
AB  - Glioblastoma (GB) often has loss of heterozygosity on the chromosomes, 1p, 10p,
      10q, 11p, 17p, 19q, 22q, and several others. In the case of chromosome 12q,
      however, it remains to be seen whether LOH occurs. Apaf-1, the apoptotic protease
      activating factor-1, located at chromosome 12q22-23, is a major effecter of the
      p53 mediated apoptosis pathway, and Apaf-1 inactivation due to chromosome 12q22
      23 LOH and hypermethylation may be involved in some of the neoplasms in
      malignancy. However, little is known about the frequency of the 12q22-23 LOH or
      the state of Apaf-1 in GB. To elucidate their involvement in GB, we analyzed a
      series of 33 GBs for chromosome 12q22-23 LOH, Apaf-1 mRNA expression, and Apaf-1
      protein expression, using microsatellite analysis, reverse transcription (RT)-PCR
      analysis, and immunohistochemical (IHC) analysis, respectively. We also evaluated
      if and how the 12q22-23 LOH correlated with the p53 gene mutation and EGFR gene
      amplification. Chromosome 12q22-23 LOH was detected in 14 (42%) of 33 cases.
      Among the examined cases with LOH at 12q22-23, a low expression of Apaf-1 mRNA
      was detected in 9 (69%) of 13 cases, and a low expression of Apaf-1 protein was
      detected in 12 (86%) of 14 cases. The 12q22-23 LOH was significantly correlated
      with low expression of mRNA and protein (p<0.05, p<0.001 respectively). The p53
      gene mutation and EGFR gene amplification were found in 13 cases (39%) and 8
      cases (24%), respectively, and these gene alterations were inversely correlated.
      However, 12q22-23 LOH had no correlations with the p53 gene mutation or EGFR gene
      amplification. Six of 9 GBs (67%) with neither p53 gene mutation nor EGFR gene
      amplification tested positive for 12q22-23 LOH. These GBs are likely to belong to
      another subset independent from the 2 common genetic subsets in GB (one with p53
      gene mutation and without EGFR gene amplification, and the other with EGFR gene
      amplification and without p53 gene mutation). Twenty-three (70%) out of the 33
      GBs with the 12q22-23 LOH also tested positive for Apaf-1 inactivation or p53
      gene mutation. This high frequency of alterations in the apoptosis-associated
      factors prompts a speculation that abrogation of the Apaf-1 and p53 mediated
      apoptosis pathway may play an important role in the tumorigenesis of GB.

PMID- 14655750
TI  - A1 adenosine receptors accumulate in neurodegenerative structures in Alzheimer
      disease and mediate both amyloid precursor protein processing and tau
      phosphorylation and translocation.
AB  - Immunostaining of adenosine receptors in the hippocampus and cerebral cortex from
      necropsies of Alzheimer disease (AD) patients shows that there is a change in the
      pattern of expression and a redistribution of receptors in these brain areas when
      compared with samples from controls. Adenosine A1 receptor (A1R) immunoreactivity
      was found in degenerating neurons with neurofibrillary tangles and in dystrophic
      neurites of senile plaques. A high degree of colocalization for A1R and betaA4
      amyloid in senile plaques and for A1R and tau in neurons with tau deposition, but
      without tangles, was seen. Additionally, adenosine A2A receptors, located mainly
      in striatal neurons in controls, appeared in glial cells in the hippocampus and
      cerebral cortex of patients. On comparing similar samples from controls and
      patients, no significant change was evident for metabotropic glutamate receptors.
      In the human neuroblastoma SH-SY5Y cell line, agonists for A1R led to a dose
      dependent increase in the production of soluble forms of amyloid precursor
      protein in a process mediated by PKC. A1R agonist induced p21 Ras activation and
      ERK1/2 phosphorylation. Furthermore, activation of A1R led to and ERK-dependent
      increase of tau phosphorylation and translocation towards the cytoskeleton. These
      results indicate that adenosine receptors are potential targets for AD.

PMID- 14655751
TI  - Selective neuronal vulnerability following mild focal brain ischemia in the
      mouse.
AB  - The evolution of cellular damage over time and the selective vulnerability of
      different neuronal subtypes was characterized in the striatum following 30-minute
      middle cerebral artery occlusion and reperfusion in the mouse. Using
      autoradiography we found an increase in the density of [3H]PK11195 binding sites-
      likely reflecting microglial activation--in the lesion border at 3 days and in
      the whole striatum from 10 days to 6 weeks. This was accompanied by a distinct
      loss of [3H]flumazenil and [3H]CGP39653 binding sites from 10 days up to 6 weeks
      reflecting neuronal loss. Brain ischemia resulted in a substantial loss of medium
      spiny projection neurons as seen at three days by Nissl staining, TUNEL and
      immunocytochemistry using antibodies against microtubule-associated protein
      (MAP2), NeuN, mu-opioid receptors, substance P, L-enkephalin, neurokinin B,
      choline acetyltransferase, parvalbumin, calretinin and somatostatin. Both patch
      and matrix compartments were involved in ischemic damage. In contrast, the
      numbers of cholinergic, GABAergic, and somatostatin-containing interneurons in
      the ischemic striatum were not different from those in the contralateral
      hemisphere at 3 and 14 days. A low density of glutamate receptors, the ability to
      sequester calcium by calcium-binding proteins and other hitherto unidentified
      factors may explain this relative resistance of interneurons to acute ischemia.

PMID- 14655752
TI  - Fatal fulminant pan-meningo-polioencephalitis due to West Nile virus.
AB  - We report a case of fatal fulminant West Nile virus (WNV) meningoencephalitis in
      an 87-year-old white male gardener. The Pennsylvania patient presented with a 3
      day history of flu-like symptoms. His hospital course was gravely precipitous
      with onset of coma, ventilator dependence, loss of cortical and brainstem
      functions within ten days of admission. Acute serum and cerebrospinal fluid
      samples revealed elevated levels of WNV IgM antibodies by ELISA as well as
      elevated CSF white blood cells, protein and glucose. A complete autopsy revealed
      a multifocal lymphocytic myocarditis and severe chronic tubulointerstitial
      nephritis. Viral culture and PCR analysis of post-mortem samples of the spleen,
      kidney and brain were positive for WNV. Histological sections from all regions of
      the brain and spinal cord demonstrated a severe, non-necrotizing, subacute, polio
      meningoencephalitis. While both gray and white matter were inflamed, gray matter
      was much more severely involved. Many gray matter nuclei showed severe neuronal
      loss with residual dying neurons surrounded by activated microglia.
      Immunohistochemical stains revealed profuse infiltration of the meninges and
      cerebral parenchyma by CD8 T-lymphocytes and perivascular B-lymphocytes. Electron
      micrographs revealed diffuse intracellular and extracellular edema but no viral
      particles were identified. Immunohistochemical and immunofluorescent staining for
      WNV filled the cytoplasm of residual neurons. West Nile virus mediates a
      predominantly polioencephalitis secondary to direct infection of neurons.

PMID- 14655754
TI  - P-glycoprotein and multidrug resistance-associated protein mediate specific
      patterns of multidrug resistance in malignant glioma cell lines, but not in
      primary glioma cells.
AB  - Understanding and overcoming multidrug resistance (MDR) may be a promising
      strategy to develop more effective pharmacotherapies for malignant gliomas. In
      the present study, human malignant glioma cell lines (n=12) exhibited
      heterogeneous mRNA and protein expression and functional activity of the mdr gene
      encoded P-glycoprotein (PGP) and MDR-associated protein (MRP). Correlation
      between mRNA expression, protein levels and functional activity was strong.
      Inhibition of PGP activity by verapamil or PSC 833 enhanced the cytotoxic effects
      of vincristine, doxorubicin, teniposide and taxol. Inhibition of MRP activity by
      indomethacin or probenecid enhanced the cytotoxic effects of vincristine,
      doxorubicin and teniposide. The human cerebral endothelial cell line, SV-HCEC,
      exhibited the strongest PGP activity of all cell lines. Five primary human
      glioblastomas and one anaplastic astrocytoma displayed heterogenous protein
      levels of PGP and MRP-1 in tumor cells and of PGP in biopsy specimens in vivo,
      but no functional activity of these proteins upon ex vivo culturing. These data
      suggest that the glioma cell line-associated MDR-type drug resistance is a result
      of long-term culturing and that cerebral endothelial, but not glioma cells, may
      contribute to MDR-type drug resistance of gliomas in vivo.

PMID- 14655753
TI  - Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes
      in Lewy body diseases.
AB  - We previously found that sustained ERK activation contributes to toxicity
      elicited by the parkinsonian neurotoxin 6-hydroxydopamine. In addition,
      substantia nigra neurons from patients with incidental Lewy body disease,
      Parkinson disease (PD), and diffuse Lewy body dementia (DLB) display abnormal
      phospho-ERK accumulations in the form of discrete cytoplasmic granules. In this
      study, we investigated the subcellular localization of phospho-ERK immunoreactive
      granules using double label confocal microscopy and immuno-electron microscopy. A
      small percentage of phospho-ERK granules co-localized with the early endosome
      marker Rab5, but not with cathepsin D, 20S proteasome beta-subunit, or cytochrome
      P450 reductase. Phospho-ERK immunoreactivity was often associated with
      mitochondrial proteins (MnSOD, 60 kDa and 110 kDa mitochondrial antigens), and
      some vesicular-appearing phospho-ERK granules appeared to envelop enlarged
      mitochondria by confocal laser scanning microscopy. Ultrastructural immuno-gold
      studies revealed phospho-ERK labeling in mitochondria and in association with
      bundles of approximately 10 nm fibrils. Heavily labeled mitochondria were
      observed within autophagosomes. As mitochondrial pathology may play a pivotal
      role in Parkinson and other related neurodegenerative diseases, these studies
      suggest a potential interaction between dysfunctional mitochondria, autophagy,
      and ERK signaling pathways.

PMID- 14655755
TI  - BAG1 over-expression in brain protects against stroke.
AB  - The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins
      (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models.
      Recently, we observed that BAG1 expression is induced during neuronal
      differentiation in the developing brain. However, the in vivo effects of BAG1
      during development and after maturation of the central nervous system have never
      been examined. We generated transgenic mice over-expressing BAG1 in neurons.
      While brain development was essentially normal, cultured cortical neurons from
      transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal
      death. Moreover, in an in vivo stroke model involving transient middle cerebral
      artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and
      substantially reduced infarct volumes compared to wild-type littermates.
      Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of
      neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential
      mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1
      displays potent neuroprotective activity in vivo against stroke, and therefore
      represents an interesting target for developing new therapeutic strategies
      including gene therapy and small-molecule drugs for reducing brain injury during
      cerebral ischemia and neurodegenerative diseases.

PMID- 14655756
TI  - Genetic alterations and aberrant expression of genes related to the phosphatidyl
      inositol-3'-kinase/protein kinase B (Akt) signal transduction pathway in
      glioblastomas.
AB  - Glioblastomas frequently carry mutations in the PTEN tumor suppressor gene on
      10q23.3. The tumor suppressor properties of Pten are closely related to its
      inhibitory effect on the phosphatidyl-inositol-3'-kinase (Pi3k)-dependent
      activation of protein kinase B (Akt) signalling. Here, we report on the analysis
      of 17 genes related to the Pi3k/Akt signalling pathway for genetic alteration and
      aberrant expression in a series of 103 glioblastomas. Mutation, homozygous
      deletion or loss of expression of PTEN was detected in 32% of the tumors. In
      contrast, we did not find any aberrations in the inositol polyphosphate
      phosphatase like-1 gene (INPPL1), whose gene product may also counteract Pi3k
      dependent Akt activation. Analysis of genes encoding proteins that may activate
      the pathway upstream of Pi3k revealed variable fractions of tumors with EGFR
      amplification (31%), PDGFRA amplification (8%), and IRS2 amplification (2%). The
      protein tyrosine kinase 2 (PTK2/FAK1) gene was neither amplified nor
      overexpressed at the mRNA level. Investigation of three genes encoding catalytic
      subunits of Pi3k (PIK3CA, PIK3CD, and PIK3C2B) revealed amplification of PIK3C2B
      (1q32) in 6 tumors (6%). Overexpression of PIK3C2B mRNA was detected in 4 of
      these cases. PIK3CD (1p36.2) and PIK3CA (3q26.3) were not amplified but PIK3CD
      mRNA was overexpressed in 6 tumors (6%). Amplification and overexpression of AKT1
      was detected in a single case of gliosarcoma. The IRS1, PIK3R1, PIK3R2, AKT2,
      AKT3, FRAP1, and RPS6KB1 genes were neither amplified nor overexpressed in any of
      the tumors. Taken together, our data indicate that different genes related to the
      Pi3k/Akt signalling pathway may be aberrant in glioblastomas.

PMID- 14655757
TI  - A 40-cM region on chromosome 14 plays a critical role in the development of virus
      persistence, demyelination, brain pathology and neurologic deficits in a murine
      viral model of multiple sclerosis.
AB  - Theiler virus persists and induces immune-mediated demyelination in susceptible
      mice and serves as a model of multiple sclerosis. Previously, we identified 4
      markers--D14Mit54, D14Mit60, D14Mit61, and D14Mit90--in a 40-cM region of
      chromosome 14 that are associated with demyelination in a cross between
      susceptible DBA/2 and resistant B10.D2 mice. We generated congenic-inbred mice to
      examine the contribution of this 40-cM region to disease. DBA Chr.14B10 mice,
      containing the chromosomal segment marked by the microsatellite polymorphisms,
      developed less spinal cord demyelination than did DBA/2 mice. More demyelination
      was found in the reciprocal congenic mouse B10.D2 Chr.14D2 than in the B10.D2
      strain. Introduction of the DBA/2 chromosomal region onto the B10.D2 genetic
      background resulted in more severe disease in the striatum and cortex relative to
      B10.D2 mice. The importance of the marked region of chromosome 14 is indicated by
      the decrease in neurological performance using the Rotarod test during chronic
      disease in B10.D2 Chr.14D2 mice in comparison to B10.D2 mice. Viral replication
      was increased in B10.D2 Chr.14D2 mice as determined by quantitative real-time RT
      PCR. These results indicate that the 40-cM region on chromosome 14 of DBA/2 mice
      contributes to viral persistence, subsequent demyelination, and loss of
      neurological function.

PMID- 14655758
TI  - Molecular characterization of BCL6 breakpoints in primary diffuse large B-cell
      lymphomas of the central nervous system identifies GAPD as novel translocation
      partner.
AB  - Primary central nervous system lymphomas (PCNSL) constitute diffuse large B-cell
      lymphomas arising in and remaining confined to the brain. Little information is
      available on cytogenetic changes in PCNSL, and recurrent chromosomal
      translocations have not yet been identified. Fluorescence in situ hybridization
      (FISH) of a series of 13 PCNSL from immunocompetent patients revealed 3 cases
      with signal patterns of a BCL6-specific probe suggesting a breakpoint in this
      oncogene locus in chromosome band 3q27. Here, we describe cloning of the
      translocation breakpoints by long-distance inverse polymerase chain reaction (LDI
      PCR) in 2 of these tumors. Both breakpoints affected the first intron of BCL6. In
      one PCNSL, the HSPCA (HSP90A) gene in 14q32.31 was identified as BCL6 partner. In
      the second lymphoma, the gene encoding glyceraldehyde-3-phosphate dehydrogenase
      (GAPD) on 12p13.31 was detected as a hitherto unknown partner of BCL6. Our
      results suggest translocation-mediated BCL6 oncogene activation as a so far
      unknown pathogenetically relevant mechanism in PCNSL.

PMID- 14655760
TI  - Molecular changes in normal appearing white matter in multiple sclerosis are
      characteristic of neuroprotective mechanisms against hypoxic insult.
AB  - Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal
      destruction of myelin, still the earliest changes that lead to lesion formation
      are not known. We have studied the gene-expression pattern of 12 samples of
      normal appearing white matter from 10 post-mortem MS brains. Microarray analysis
      revealed upregulation of genes involved in maintenance of cellular homeostasis,
      and in neural protective mechanisms known to be induced upon ischemic
      preconditioning. This is best illustrated by the upregulation of the
      transcription factors such as HIF-1alpha and associated PI3K/Akt signalling
      pathways, as well as the upregulation of their target genes such as VEGF receptor
      1. In addition, a general neuroprotective reaction against oxidative stress is
      suggested. These molecular changes might reflect an adaptation of cells to the
      chronic progressive pathophysiology of MS. Alternatively, they might also
      indicate the activation of neural protective mechanisms allowing preservation of
      cellular and functional properties of the CNS. Our data introduce novel concepts
      of the molecular pathogenesis of MS with ischemic preconditioning as a major
      mechanism for neuroprotection. An increased understanding of the underlying
      mechanisms may lead to the development of new more specific treatment to protect
      resident cells and thus minimize progressive oligondendrocyte and axonal loss.

PMID- 14655759
TI  - TRAIL triggers apoptosis in human malignant glioma cells through extrinsic and
      intrinsic pathways.
AB  - Many malignant glioma cells express death receptors for tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL), yet some of these cells are resistant
      to TRAIL. Here, we examined signaling events in TRAIL-induced apoptosis and
      searched for therapeutic agents that could overcome TRAIL resistance in glioma
      cells. TRAIL induced apoptosis through death receptor 5 (DR5) and was mediated by
      caspase-8-initiated extrinsic and intrinsic mitochondrial pathways in sensitive
      glioma cell lines. TRAIL also triggered apoptosis in resistant glioma cell lines
      through the same pathways, but only if the cells were pretreated with
      chemotherapeutic agents, cisplatin, camptothecin and etoposide. Previous studies
      suggested that this was due to an increase in DR5 expression in wild-type TP53
      cells, but this mechanism did not account for cells with mutant TP53. Here, we
      show that a more general effect of these agents is to downregulate caspase-8
      inhibitor c-FLIP(S) (the short form of cellular Fas-associated death domain-fike
      interleukin-1-converting enzyme-inhibitory protein) and up-regulate Bak, a pro
      apoptotic Bcl-2 family member, independently of cell's TP53 status. Furthermore,
      we showed that TRAIL alone or in combination with chemotherapeutic agents,
      induced apoptosis in primary tumor cultures from patients with malignant gliomas,
      reinforcing the potential of TRAIL as an effective therapeutic agent for
      malignant gliomas.

PMID- 14655761
TI  - Autosomal dominant adult neuronal ceroid lipofuscinosis: a novel form of NCL with
      granular osmiophilic deposits without palmitoyl protein thioesterase 1
      deficiency.
AB  - We describe the neuropathological and biochemical autopsy findings in 3 patients
      with autosomal dominant adult neuronal ceroid lipofuscinosis (ANCL, Parry type;
      MIM 162350), from a family with 6 affected individuals in 3 generations.
      Throughout the brain of these patients, there was abundant intraneuronal
      lysosomal storage of autofluorescent lipopigment granules. Striking loss of
      neurons in the substantia nigra was found. In contrast, little neuronal cell loss
      occurred in other cerebral areas, despite massive neuronal inclusions. Visceral
      storage was present in gut, liver, cardiomyocytes, skeletal muscle, and in the
      skin eccrine glands. The storage material showed highly variable immunoreactivity
      with antiserum against subunit c of mitochondrial ATP synthase, but uniform
      strong immunoreactivity for saposin D (sphingolipid activating protein D).
      Protein electrophoresis of isolated storage material revealed a major protein
      band of about 14 kDa, recognized in Western blotting by saposin D antiserum (but
      not subunit c of mitochondrial ATPase (SCMAS) antiserum). Electron microscopy
      showed ample intraneuronal granular osmiophilic deposits (GRODs), as occurs in
      CLN1 and congenital ovine NCL. These forms of NCL are caused by the deficiencies
      of palmitoyl protein thioesterase 1 and cathepsin D, respectively. However,
      activities of these enzymes were within normal range in our patients. Thus we
      propose that a gene distinct from the cathepsin D and CLN1-CLN8 genes is
      responsible for this autosomal dominant form of ANCL.

PMID- 14655762
TI  - Minor contribution of bone marrow-derived endothelial progenitors to the
      vascularization of murine gliomas.
AB  - Until recently, it was generally accepted that the vascularization of solid
      tumors occurred exclusively through the sprouting and co-option from pre-existing
      blood vessels. Growing evidence now suggests that bone marrow-derived endothelial
      progenitor cells (EP) circulate in the blood and may play an important role in
      the formation of new blood vessels in certain tumors. Whether endothelial
      progenitors participate in the vascularization of brain tumors has not yet been
      evaluated. In this study, we examined the contribution of EP to tumor
      angiogenesis in a murine glioma tumor model. Donor bone marrow cells obtained
      from transgenic mice constitutively expressing beta-galactosidase or GFP either
      ubiquitously or transcriptionally regulated by an endothelial specific promotor
      Tie-2 were injected into lethally irradiated adult mice. After bone marrow
      reconstitution by donor cells, mice were implanted with syngeneic GL261 murine
      glioma cells. Morphological and confocal 3-dimensional analysis showed that the
      majority of the engrafted donor marrow cells were expressing hematopoietic and/or
      microglia markers, but did not appreciably contribute to the tumor vasculature.
      Implantation of glioma cells genetically engineered to overexpress VEGF produced
      highly vascularized tumors. However, the number of endothelial progenitors
      incorporated in the tumor vasculature did not increase. These data strongly
      suggest that neovascularization in the brain might fundamentally be regulated by
      the sprouting of pre-existing vessels and implicate that circulating endothelial
      progenitors do not play a significant role in this process.

PMID- 14655763
TI  - Independent molecular development of metachronous glioblastomas with extended
      intervening recurrence-free interval.
AB  - Two metachronous glioblastomas with different cerebral locations in a 53-year-old
      long-term survival patient were analyzed by multiple genetic approaches. Using
      comparative genomic hybridization a different pattern of chromosomal aberrations
      was observed, with 19 imbalances in the first tumor and only 2 imbalances in the
      second. Sequence analysis revealed a distinct mutation profile in each tumor,
      with amino acid substitutions in the p53 and PTEN genes only in the first tumor,
      ie, p53 in codon 273 (CGT-->TGT, Arg-->Cys) and PTEN in codon 336 (TAC-->TTC, Tyr
      ->Phe). A splicing acceptor site PTEN mutation (IVS8-2A>G) was observed only in
      the second GBM. EGFR amplification, mutations of p16INK4a/CDKN2A or p14ARF were
      not observed. According to the results of p53 mutational analysis and EGFR
      amplification studies, the first tumor is classified as a type 1 GBM, whereas the
      alterations in the second one are different from those typically encountered in
      type 1 or type 2 tumors. In conclusion, our data strongly suggest that the
      metachronous tumors in this patient are exceptional in that they developed
      independently from each other. Whether the molecular features of the first
      glioblastoma are associated with the notably extended recurrence-free period of 5
      years remains to be elucidated.

PMID- 14655764
TI  - Human monoclonal IgM antibody promotes CNS myelin repair independent of Fc
      function.
AB  - The human monoclonal IgM antibody sHIgM22 and mouse IgM monoclonal antibody 94.03
      bind to oligodendrocytes, induce calcium signals in cultured glial cells, and
      promote remyelination in mouse models of multiple sclerosis. In order to address
      the mechanisms employed by these antibodies to promote CNS repair, bivalent
      monomers, F(ab')2 fragments, and monovalent forms of these antibodies were
      investigated to determine whether they exhibit the same remyelinating potential
      as the intact IgMs. The two antibodies displayed different structural
      requirements for retention of function. Antibody sHIgM22 remained functional even
      when reduced to a bivalent F(ab')2 fragment, while disruption of the pentameric
      structure of antibody 94.03 destroyed its functional properties. Competition
      studies demonstrated that the two antibodies recognize different entities on the
      surface of glial cells. These results indicate that the constant region and
      pentameric structure of IgM is not always necessary for the stimulation of myelin
      repair, eliminating the requirement for IgM immune effector functions in this
      process. The ability of the antibodies to cross-link cell surface determinants on
      oligodendrocytes appears to be an essential aspect of the mechanism of cellular
      activation. The finding that two antibodies, which induce similar in vivo
      effects, bind to different structures, and have different cross-linking
      requirements suggests that activation of glial cells involves the rearrangement
      of a complex membrane compartment.

PMID- 14655765
TI  - Differential expression of the chemokine receptors CX3CR1 and CCR1 by microglia
      and macrophages in myelin-oligodendrocyte-glycoprotein-induced experimental
      autoimmune encephalomyelitis.
AB  - Chemokines are important for the recruitment of immune cells into sites of
      inflammation. To better understand their functional roles during inflammation we
      have here studied the in vivo expression of receptors for the chemokines
      CCL3/CCL5/CCL7 (MIP-1alpha/RANTES/MCP-3) and CX3CL1 (fractalkine), CCR1 and
      CX3CR1, respectively, in rat myelin oligodendrocyte glycoprotein-induced
      experimental autoimmune encephalomyelitis. Combined in situ hybridization and
      immunohistochemistry demonstrated intensely upregulated CCR1 mRNA expression in
      early, actively demyelinating plaques, whereas CX3CR1 displayed a more
      generalized expression pattern. CX3CR1 mRNA expressing cells were identified as
      microglia on the basis of their cellular morphology and positive GSA/B4 lectin
      staining. In contrast, CCR1 mRNA was preferentially expressed by ED1+ GSA/B4+
      macrophages. The notion of differential chemokine receptor expression in
      microglia and monocyte-derived macrophages was corroborated at the protein level
      by extraction and flow cytometric sorting of cells infiltrating the spinal cord
      using gating for the surface markers CD45, ED-2 and CD11b. These observations
      suggest a differential receptor expression between microglia and monocyte-derived
      macrophages and that mainly the latter cell type is responsible for active
      demyelination. This has great relevance for the possibility of therapeutic
      intervention in demyelinating diseases such as multiple sclerosis, for example by
      targeting signaling events leading to monocyte recruitment.

PMID- 14655766
TI  - Will preventing protein aggregates live up to its promise as prophylaxis against
      neurodegenerative diseases?
AB  - Protein aggregation and misfolding characterize most age-related
      neurodegenerative diseases including Alzheimer, Parkinson and Huntington
      diseases. Protein aggregation has generally been assumed to be responsible for
      neurodegeneration in these disorders due to association and genetics. However,
      protein aggregation may, in fact, be an attempt to protect neurons from the
      stress resulting from the disease etiology. In this review, we weigh the evidence
      of whether removal of amyloids, aggregates and neuronal inclusions represent a
      reasonable strategy for protecting neurons.

PMID- 14655767
TI  - April 2003: 55-year-old male with necrotic pontine lesion.
AB  - The April Case of the Month (COM). A 55-year-old male with history of diabetes
      mellitus presented with progressive loss of sensitivity on the left side of the
      body and horizontal diplopia. Symptoms appeared after a right basal pneumonia one
      month before admission. A CT scan showed an large inoperable lesion in the pons.
      The patient was treated with corticoids. One week later, the patient showed
      general deterioration. The fifth and sixth right cranial nerves were affected.
      Ataxia and disorders in swallowing were also present. A second CT scan showed
      that the pontine mass had become larger. The patient died 7 days after his
      admission and the autopsy was limited to CNS. The right middle cerebellar
      peduncle showed a 2-cm well-defined white brownish necrotic lesion that extended
      to the pons and periventricular gray matter. Microscopic examination revealed
      toxoplasmosis, which was confirmed by immunohistochemical studies. The brain
      tissue was negative for HIV by PCR. Toxoplasmosis is a well-known complication of
      AIDS, and has been reported in post-transplant patients as well, but only a few
      reports of toxoplasmosis in diabetics have been reported.

PMID- 14655768
TI  - May 2003: 57-year-old-woman with acute loss of strength in her right upper
      extremity and slurred speech.
AB  - The May 2003 COM. A 57-year-old woman presented with slurring of her speech and
      right arm weakness. Her past medical history included idiopathic hypertrophic
      subendocardial stenosis (IHSS), arthritis, asthma, congestive heart failure,
      hypertension and NIDDM. Neurological examination showed persistent word finding
      difficulty but her motor and sensory function had essentially returned to normal.
      Extensive laboratory studies were unrevealing. Imaging studies showed a meningeal
      lesion over the left posterior parietal lobe and the findings suggested an
      infectious or inflammatory process. A biopsy of the involved dura and meninges
      was performed and revealed leptomeningeal Rosai-Dorfman disease. Emperipolesis
      was noted. The finding of emperipolesis is characteristic of Rosai-Dorfman
      disease of the leptomeninges, but in 30% of cases, this feature will not be
      identified. Large pale histiocytes of Rosai-Dorfman disease are immunoreactive
      for S-100 protein and KP1, but negative for CD1a. The differential diagnosis of a
      chronic inflammatory infiltrate containing numerous, large histiocytes includes
      granulomatous diseases such as Wegener graulomatosis and sarcoid, Hodgkin
      disease, and Langerhans histiocytosis. CNS Rosai-Dorfman most commonly involves
      patients between 20- and 40-years-old, with a slight male predominance.
      Approximately 75% of cases are intracranial, whereas 20% involve the spine. Over
      90% of CNS Rosai-Dorfman cases involve the leptomeninges and are seen by
      neuroimaging as a dural-based, contrast-enhancing masses that often elicit
      vasogenic edema in the underlying brain. Thus, clinically and radiologically, the
      disease is thought to represent meningioma. Leptomeningeal Rosai-Dorfman disease
      is considered a benign condition and in most cases surgical resection is the
      treatment of choice. Although the number of cases in the literature is small,
      disease progression following surgical resection is uncommon. Little is known
      regarding the pathogenesis of Rosai-Dorfman disease. Most have suggested that it
      represents either an autoimmune disease or a reaction to an infectious agent that
      has yet to be discovered. Currently it is best considered a benign, idiopathic
      histiocytosis.

PMID- 14655769
TI  - June 2003: 33-year-old male with a frontal lobe mass.
AB  - The June 2003 COM. A 33-year-old male with a history of seizures was found to
      have an intra- and extra-axial frontal lobe mass. The histology of the resected
      tumor showed a meningioma with underlying meningioangiomatosis.
      Meningioangiomatosis (MA) is a benign intracortical plaque-like proliferation of
      meningothelial cells, microvasculature and fibroblast-like cells probably of
      hamartomatous origin. Very rarely, MA is associated with an overlying meningioma
      as in this case. When MA is accompanied by a meningioma, it is generally not
      associated with clinical evidence of neurofibromatosis. It is important to
      distinguish MA from an invasive meningioma, because of its favorable prognosis
      after resection.

PMID- 14655770
TI  - Learning curve.

PMID- 14655771
TI  - What is your diagnosis? Sweet Syndrome (acute febrile neutrophilic dermatosis).

PMID- 14655772
TI  - Annular pustules in Kawasaki disease: a further case indicating the association
      with psoriasis?
AB  - We report the case of a 4-year-old girl with Kawasaki disease (KD), or
      mucocutaneous lymph node syndrome, who presented with an annular pustular
      eruption. Targetlike erythematous and scaly patches were observed after
      resolution of the pustules. A biopsy of the skin was performed, and results
      showed spongy pustules not associated with the intraepidermal eccrine duct.
      Generalized pustular eruption, including pustular psoriatic lesions, has been
      described in KD. However, to our knowledge, this is the first report of annular
      pustular eruption mimicking annular pustular psoriasis in KD.

PMID- 14655773
TI  - A different kind of residency--a different kind of resident.
AB  - The military dermatologist requires a set of job skills beyond that of the
      civilian dermatologist. When military dermatologists complete their training,
      they must be prepared to function in remote locations with limited subspecialty
      support. Military dermatologists must be competent in the broad range of
      disciplines that encompass dermatology and have special expertise in tropical and
      environmental dermatology. They also must maintain a broad knowledge of
      biological and chemical agents. Three US military training programs currently
      exist. The largest, in San Antonio, Texas, was formed in 1996 when Wilford Hall
      Medical Center and Brooke Army Medical Center merged their resources and
      residents to create a single large program. The contributions of military
      dermatologists are discussed in the context of how the joint Army/Air Force
      program is structured to meet a broad set of needs.

PMID- 14655774
TI  - The military and academic dermatology.

PMID- 14655775
TI  - The current status of US Army dermatology.

PMID- 14655776
TI  - Lupus mucinosis: a case report and review of cutaneous lupus.
AB  - Lupus mucinosis (LM) is a rare disorder found only in patients with systemic
      lupus erythematosus (SLE) or discoid lupus erythematosus (DLE). We describe a
      patient with lupus mucinotic nodules as the initial presenting sign of SLE. We
      further discuss other forms of cutaneous lupus and contrast them with our
      findings.

PMID- 14655777
TI  - Cutaneous tuberculosis and other skin diseases in hospitalized, treated pulmonary
      tuberculosis patients in the Philippines.
AB  - A cross-sectional study of 425 hospitalized patients with pulmonary tuberculosis
      (PTB) was conducted to look for the presence of cutaneous tuberculosis (CTB) and
      other skin diseases. Because PTB is one of the leading causes of morbidity and
      mortality in the Philippines, a high number of CTB was expected despite
      antituberculosis (anti-TB) treatment. Scarring (post-CTB) in Filipinos usually is
      obvious and visible because of their brown skin. However, no scarring was
      observed in our patients. Other skin diseases seen were tabulated and followed
      the frequency rates seen in charity and private hospitals or clinics reported in
      previously published literature. We therefore conclude that CTB is rare in
      patients with PTB, especially in treated cases.

PMID- 14655778
TI  - Lichen planus actinicus.
AB  - Lichen planus actinicus is a photodistributed variant of lichen planus that most
      often occurs in individuals with dark complexions. Sunlight seems to be a
      triggering factor in most cases. Several clinical morphologic patterns have been
      described, and multiple therapies with variable results have been used. The
      lesions in some patients may remit spontaneously with sun avoidance.

PMID- 14655779
TI  - Bullous contact dermatitis caused by self-applied crushed Paederus fuscipes for
      the treatment of vitiligo.
AB  - Paederus dermatitis is a linear, blistering contact dermatitis caused by pederin,
      a potent vesicant agent that is contained in insects belonging to the genus
      Paederus. This form of dermatitis usually occurs accidentally in those who have
      contact with this insect during the summer season. We report a peculiar case of a
      patient developing severe chemical burnlike lesions after application to her skin
      of many crushed Paederus fuscipes that she collected from the soil of a riverbank
      in the early spring for the treatment of her vitiligo.

PMID- 14655780
TI  - Verrucous porokeratosis of Mibelli on the buttocks mimicking psoriasis.
AB  - The typical presentation of porokeratosis of Mibelli is of a solitary plaque with
      a prominent raised border cleaved by a central furrow. The central portion of the
      plaque is usually slightly atrophic. The plaques vary in size from a few
      millimeters to several centimeters in diameter and tend to be acrally
      distributed, though they can occur on any part of the body. We report an unusual
      case of verrucous porokeratosis of Mibelli, localized to the natal cleft, that
      mimicked psoriasis. This entity, though unusual, is not unique. Two similar cases
      of verrucous porokeratosis of Mibelli limited to the natal cleft region and
      resembling psoriasis have been reported in the British literature. Verrucous
      porokeratosis of Mibelli localized to the natal cleft appears to be a distinct
      clinical entity that can mimic psoriasis. Better recognition of this form of
      porokeratosis of Mibelli may result in earlier diagnosis and initiation of
      appropriate therapy.

PMID- 14655781
TI  - Successful treatment of recalcitrant palmoplantar psoriasis with etanercept.
AB  - Palmoplantar psoriasis is a disabling condition characterized by recurrent crops
      of sterile pustules with associated erythema, fissuring, and scaling. Genetic and
      environmental factors have been implicated in its etiology. Topical treatments
      are frequently ineffective. Other treatment options include systemic retinoids,
      psoralen-UVA (PUVA), and a combination of both. We report a case of successful
      treatment of recalcitrant palmoplantar psoriasis with etanercept in a 59-year-old
      woman unresponsive to other treatment modalities.

PMID- 14655782
TI  - Urticarial vasculitis and dermatomyositis in a patient with nasopharyngeal
      carcinoma.
AB  - Urticarial vasculitis has rarely been described in association with polymyositis.
      We report the case of a 37-year-old man with dermatomyositis and nasopharyngeal
      carcinoma who presented initially with urticarial vasculitis. The lesions of
      urticarial vasculitis were initially photodistributed, indicating
      photosensitivity. The patient was treated with systemic steroids, chemotherapy
      (cisplatin and fluorouracil), and radiation therapy. The tumor and urticarial
      vasculitis completely resolved, and the myositis improved.

PMID- 14655785
TI  - Therapeutic choices for the discomforts of labor.
AB  - Health care providers including nurses and childbirth educators are crucial
      resources for childbearing families for accurate and current information
      regarding nonpharmacologic and pharmacologic interventions available for pain
      management in labor. All medications that are administered to laboring women have
      maternal and fetal effects. In order to assist women in the decision for relief
      of labor discomforts, health care professionals must be knowledgeable of the
      chemical actions and adverse effects of all medications offered to women in
      labor. This article discusses various types of therapeutic options used for pain
      management for the relief of labor discomfort.

PMID- 14655784
TI  - Medication formulation affects quality of life: a randomized single-blind study
      of clobetasol propionate foam 0.05% compared with a combined program of
      clobetasol cream 0.05% and solution 0.05% for the treatment of psoriasis.
AB  - For topical medications commonly used to treat dermatologic conditions, outcomes
      may be affected by the choice of delivery vehicles. The aim of this study was to
      compare quality of life (QOL), effectiveness, user satisfaction, and cost
      effectiveness of 2 clobetasol regimens for the treatment of psoriasis over 14
      days. In a single-blind design, 32 patients randomized into 2 groups applied
      either clobetasol foam 0.05% to the skin and scalp or combination clobetasol
      cream 0.05% to the skin and clobetasol solution 0.05% to the scalp. Psoriasis
      severity was measured using the standardized Psoriasis Area and Severity Index
      (PASI) and self-administered PASI (SAPASI). QOL was assessed via the EuroQoL-5D
      (EQ-5D) questionnaire and Dermatology Life Quality Index (DLQI). Cost
      effectiveness was measured by the amount of medication used per body surface area
      (BSA) treated and by cost per point improvement in PASI score. In this study, a
      foam formulation performed better than a cream/solution combination by several
      measures. A greater absolute improvement in psoriasis severity was seen in the
      group using the foam than in the group using the cream/solution (mean decrease in
      PASI=5.0 vs 3.3, P=.05). The PASI score in the foam group decreased by 41% versus
      35% in the cream/solution group (P=.17). In scalp psoriasis, the group using the
      foam had greater improvement in both absolute (P=.03) and percentage (P=.03)
      terms and than the solution group. When measuring global QOL, foam users had a
      significantly greater increase in EQ-5D than those using the cream/solution in
      absolute (P=.05, P=.02) and percentage (P=.04, P=.02) terms (first and second
      survey components, respectively). Differences in improvement of skin-specific
      QOL, quantified by DLQI scores between groups, were suggested but not
      statistically significant. Patients using foam spent less time applying
      medication compared with previous topical medications (P<.001). No significant
      difference in cost was appreciated between foam and cream/solution over the
      period after controlling for BSA (8.18 dollars vs 7.05 dollars per percentage BSA
      affected, P=.30).

PMID- 14655783
TI  - The Kobner phenomenon and psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) affects a large percentage of patients with psoriasis.
      Similar to the cutaneous disease of psoriasis, PsA displays an isomorphic
      response (ie, the propensity to develop at traumatized sites). In some patients,
      traumatized joints that subsequently develop PsA are the initial manifestation of
      psoriasis, preceding the skin disease by months to years. Dermatologists should
      screen patients with psoriasis for accompanying PsA and consider recently
      traumatized joints that remain arthritic to be a component of this disease.

PMID- 14655787
TI  - Folic acid and neural tube defects in pregnancy: a review.
AB  - Neural tube defects (NTDs) are common fetal malformations. They are
      multifactorial in origin, with folic acid as the primary known environmental
      factor. It is recommended that all women consume 0.4 mg of synthetic folic acid
      daily if there is any possibility of becoming pregnant. Women who have had a
      previous pregnancy affected by NTD should increase their folic acid intake to 4.0
      mg daily periconceptually. The purpose of this article is to review the
      relationship between folic acid and NTDs. It also discusses how the knowledge and
      use of folic acid has affected the incidence of NTDs, and ways in which the
      knowledge and use of folic acid before pregnancy can be increased.

PMID- 14655788
TI  - Adapting the neonatal intensive care environment to decrease noise.
AB  - A protocol of environmental noise reduction was developed and tested over a 14
      month period in a 70-bed tertiary care neonatal intensive care unit (NICU).
      Evidence-based research and a detailed sound assessment guided the development of
      the protocol. Modifications of caregiving activities and categorized changes in
      the physical environment were specific to the NICU tested; however, guidelines
      for adapting the protocol to other NICUs are explained as well as methods for
      implementation to promote staff awareness and cooperation are reviewed.

PMID- 14655786
TI  - Neuraxial analgesia for labor and birth: implications for mother and fetus.
AB  - Women are better educated today on issues related to labor and childbirth. Pain
      management options for the woman in labor have changed dramatically over the last
      decade. Systemic analgesia and dense-motor-blockade regional analgesia/anesthesia
      have become less common for childbirth while the use of newer neuraxial and
      regional techniques, with minimal motor blockade, have become more popular. The
      shift from regional anesthesia with significant motor-blockade during labor,
      where the woman is a passive participant during the labor and birth, to a
      collaborative approach for pain management, where the woman becomes an active
      participant, has resulted in a new philosophy of analgesia for labor and birth.
      This article provides a review of current neuraxial analgesia/anesthesia
      techniques used for pain management in labor and birth and their implications for
      the perinatal nurse.

PMID- 14655789
TI  - Nursing assessment of infant pain.
AB  - This study compared how nurses perceived their assessment of infant pain and how
      the pain was actually assessed in an intensive care unit. A descriptive design
      was used to collect data about nurses beliefs and documentation practices related
      to pain assessment in infants. An anonymous subset of the unit nurses (n = 24)
      responded to a questionnaire regarding infant pain assessment. Pain assessment
      documentation of the unit nurses was examined in a retrospective chart review (n
      = 107). Results showed an inconsistency between what nurses believe about infant
      pain as sessment and the documentation practice in the unit. According to the
      questionnaire, the nurses believed that pain assessment was important to
      providing effective pain relief and that nurses are capable of assessing infant
      pain. However, it was not evident in the documentation that nurses used pain
      tools or other means to document their evaluations of infant pain or the infant's
      response to pain medication interventions. CONCLUSION: Greater consistency of
      nurses in documenting pain assessment, thereby improving care provider
      communication of an infant's pain experience, is needed to improve the standard
      of care in managing infant pain.

PMID- 14655791
TI  - Egg and embryo donation and the meaning of motherhood.
AB  - As part of a larger study on donor-assisted conception, this paper reports
      research which explored the ways in which women who have donated or received eggs
      or embryos interpret such donations in the context of motherhood. Narrative
      analysis of women's accounts revealed that egg and embryo donations are not
      interpreted as incompatible with motherhood; that they may be explained as
      contributing to the significance of motherhood through the desire to assist some
      women to whom motherhood has been denied; and that the welfare of offspring of
      donated eggs and embryos is considered by donors. Differences were found between
      the meanings of egg donation and embryo donation, including likening eggs to
      cells and embryos to children, and in donors the expression of stronger maternal
      connection to the offspring of donated embryos. These accounts reveal individual
      variation, complexity, and change, reflecting (among other things) the dynamic
      process of narrative revision.

PMID- 14655790
TI  - Management of pain from heel stick in neonates: an analysis of research conducted
      in Thailand.
AB  - The heel stick procedure is the most common painful procedure performed in
      preterm and full-term neonates. Various nonpharmacologic interventions have been
      used for pain relief. However, the magnitude of the effect of different
      interventions has received little attention. In this study, 4 eligible studies
      conducted in Thailand, focusing on the effects of interventions on pain responses
      to heel stick procedure in neonates, were obtained for analysis. Swaddling in
      full-term newborns was found to have the largest mean effect size (dmn = 0.79).
      However, the moderate-to-large effect sizes (dmn = 0.5-0.75) of positioning in
      preterm newborns tended to exist throughout the poststick period while the effect
      sizes of other interventions decreased over time. The effect sizes of these
      interventions for physiological responses varied.

PMID- 14655793
TI  - Do attitude toward cancer, sense of coherence and family high risk predict more
      psychological distress in women referred for a breast cancer examination?
AB  - OBJECTIVE: The study focuses on the connection between attitude toward cancer,
      sense of coherence and family history of breast cancer, on the one hand, and
      psychological distress on the other among women who are referred for breast
      cancer examination following a medical examination prompted by a complaint of
      "feeling something in the breast." METHOD: A sample of 314 women referred to a
      breast health clinic in northern Israel completed questionnaires that measured
      psychological distress (Brief Symptom Inventory), personal resources (the Sense
      of Coherence Scale), and mindset (Attitude to Cancer Treatment Scale). RESULTS: A
      weak sense of coherence and a more negative attitude toward cancer (i.e., viewing
      victims of cancer with pity; viewing the illness as a death sentence; harboring a
      fear of death from cancer) predict a high level of psychological distress while
      awaiting an examination. A family history of breast cancer, or a first-time
      examination, were not found to be predictors of greater psychological distress.
      CONCLUSION: Learning cognitive behavioral coping skills, as well as access to
      information on cancer and treatment in order to change attitude toward cancer,
      are needed.

PMID- 14655792
TI  - The cancer screening project for women: experiences of women who partner with
      women and women who partner with men.
AB  - The Cancer Screening Project for Women is a study about the experiences of
      legally unmarried women with breast, cervical, and colorectal cancer screening.
      During the initial phase of the study, we conducted focus groups to explore
      factors that influence unmarried women's decisions about cancer screenings. Women
      were invited to attend one of four group discussions: (1) never married women who
      either partner with women (WPW) or with both women and men (WPWM), (2) previously
      married women who now partner either with women (WPW) or with both women and men
      (WPWM), (3) never married women who partner with men (WPM), and (4) previously
      married women who partner with men (WPM). Twenty-eight women attended the focus
      groups, 14 WPW and 14 WPM. Several barriers to screening were consistent across
      the groups and included lack of acknowledgement and validation in medical
      settings, administrative barriers, pain, and concerns about body image. WPW
      specifically discussed fears about discrimination if and when they acknowledge
      their sexual orientation. WPW also described how women who express their gender
      androgynously are more likely to avoid health care facilities. Further studies
      are needed to determine if the themes we identified are consistent among larger
      samples of unmarried women.

PMID- 14655794
TI  - "At risk" women who think that they have no chance of getting HIV: self-assessed
      perceived risks.
AB  - During the past two decades, a fair amount of inconclusive research has been
      conducted to examine the relationship between perceived risk of contracting HIV
      and actual HIV risk behavior practices. The present study examines HIV risk
      perceptions among a sample of 250 urban, economically-disadvantaged, primarily
      minority women. In particular, we focus on differences between those saying that
      they have no chance whatsoever of contracting HIV and those who indicated at
      least some possibility of becoming HIV-infected. Three research questions are
      addressed: (1) Are there differences between these groups attributable to their
      risk behavior practices? (2) To what extent do women who think that they are not
      at risk for HIV engage in risky behaviors that could expose them to HIV? (3) What
      are the most salient predictors of the women's perceived risk classification?
      Results showed that women perceiving themselves to have at least some HIV risk
      engaged in higher rates of risky behaviors than their counterparts who perceived
      themselves to have no possibility of contracting HIV. Despite this finding, more
      than one-half of the "no perceived risk of HIV" sample had engaged in at least
      one risky practice during the preceding year and more than one-quarter had
      engaged in at least two such behaviors. Age, childhood maltreatment experiences,
      self-esteem, number of HIV risk behaviors practiced, amount of illegal drug use
      reported, and number of times having sex were significant predictors of women's
      perception of having some HIV risk versus having no HIV risk.

PMID- 14655799
TI  - Helpful hints for injections of wrist and hand region.

PMID- 14655795
TI  - Measures and correlates of resilience.
AB  - OBJECTIVE: We collected data on several aspects of resilience and related them to
      personal perceptions of breast cancer risk and worry about cancer. METHODS: As
      part of an ongoing series of studies to examine women's needs for and responses
      to breast cancer risk counseling, women with a family history of breast cancer (n
      = 357) completed questionnaires as part of their ongoing follow-up for counseling
      interventions. The questionnaire contained several measures of resilience:
      Optimism, the Life Attitude Profile-Revised, and single item scales measuring the
      worst to best possible life for past, present and future time periods. We also
      measured quality of life, social desirability, cancer worry, and personal
      perceived risk of breast cancer. We analyzed the relationships among resilience
      variables to determine the best measures of resilience from among the measures
      used. We then related resilience measures to breast cancer worry and risk.
      RESULTS: Overall, the relationships among the resilience variables varied
      considerably. The average worst to best possible life ratings increased from past
      to present to future, and only current and future estimates were highly
      correlated (r = .62; p < 0.01). Optimism was not correlated with any other
      resilience variable, suggesting that it is measur- ing some other construct. None
      of the resilience measures were highly correlated with social desirability,
      indicating that resilience is not simply a measure of self-promotion. Quality of
      life measures correlated most highly with present life ratings (r = .54; p <
      0.01). Perceived cancer worry and risk were negatively correlated with future and
      present life ratings, but at very low levels (r' s = -.20 and -.21; p < 0.001 for
      both). Analyses predicting risk and worry using a subset of resilience variables
      are presented. CONCLUSION: These data will help to identify resilient women and
      how they view and manage their health risks.

PMID- 14655796
TI  - Use of VA health care services by women veterans: findings from a national
      sample.
AB  - The Department of Veterans Affairs (VA) has a Congressional mandate but few
      empirical data on which to design and improve national health care services for
      women. We examined characteristics associated with women's current, former and
      non-use of the VA health care system. The study included 1,500 female veterans
      sampled from the Department of Veterans Affairs National Registry of Women
      Veterans. Women completed a 45-minute telephone survey assessing multiple domains
      of functional status and health service use. Using multivariate logistic
      regression, use of VA health care was associated with older age, more education,
      not being married, lower rates of insurance coverage, and poorer physical and
      psychological health. Women who were former users of VA health care were more
      likely to be ethnic minorities, have children, served less time in the military,
      had higher rates of insurance coverage and better physical and psychological
      health than current users. Prominent military experiences (e.g., service in a war
      zone, exposure to trauma) were associated with former use and never using the VA
      health care system. Women who use VA health care are at greater economic, social,
      and health risk than nonusers, factors that have personal implications for the
      veteran as well as cost and service implications for VA. Additional research is
      needed to better understand the role of military experiences in women veterans'
      choice of health care.

PMID- 14655800
TI  - Is duct tape occlusion therapy an effective treatment of warts?

PMID- 14655798
TI  - Survey on the programs of Sanhujori centers in Korea as the traditional
      postpartum care facilities.
AB  - Sanhujori is the term used for the traditional Korean concept of non-professional
      postpartum care after delivery or abortion. Recently, postpartum care has been
      transferred to facilities appropriately named Sanhujori centers. This study
      investigates the programs offered at Sanhujori centers in order to understand the
      effects of this new type of health care delivery system on postpartum care. A
      qualitative descriptive study was conducted that included twenty-seven centers.
      Data were collected via face-to-face interviews followed by telephone interviews
      conducted from May first until the eighteenth of 2001. The findings permitted
      description of the general characteristics of Sanhujori centers. Programs for
      physical recovery, psychosocial recovery, postpartum education, parents-infant
      bonding, and baby care were analyzed and discussed.

PMID- 14655797
TI  - Attitudes toward menopause in relation to symptom experience in Puebla, Mexico.
AB  - OBJECTIVE: To examine how attitudes toward menopause were associated with symptom
      frequencies after controlling for menopause status and level of education.
      METHODS: Women aged 28-70 (n = 755) were interviewed from May, 1999 through
      August, 2000 in the city of Puebla, Mexico. Over 90% of the sample were aged 40
      60. Participants were asked to select from a set of dichotomies to describe "how
      a woman feels during menopause." Symptom frequencies were assessed by a checklist
      of everyday complaints experienced during the two weeks before interview. Symptom
      presence or absence was examined in relation to attitudes while controlling for
      menopause status and level of education using binary logistic regression
      analyses. RESULTS: The majority of respondents said that a menopausal woman feels
      "insecure" and "unattractive" yet "complete," "necessary," and "successful." Pre
      menopausal women and respondents who had undergone a hysterectomy were more
      likely to express negative attitudes. Post-menopausal women and women with fewer
      years of education were significantly more likely to report symptoms such as hot
      flashes, joint aches, and nervous tension. A range of negative attitudes were
      associated with nervous tension, feeling blue, and head aches; however, only a
      few negative attitudes were significantly predictive of estrogen-related symptoms
      (e.g., hot flashes). CONCLUSIONS: There is a high value placed on both external
      appearance and familial responsibility among menopausal women in Puebla, Mexico,
      and negative characterizations of menopause reflect these values. Negative
      attitudes were associated with more frequently reported symptoms compared with
      positive attitudes. The challenge remains to separate factors related to the
      hormonal changes of menopause from those not associated with hormonal changes to
      better understand symptom experience.

PMID- 14655801
TI  - Primary care and primary immunodeficiencies.

PMID- 14655802
TI  - Public health--the role of family physicians.

PMID- 14655803
TI  - DNA, Nobel Prizes, and succinct writing.

PMID- 14655804
TI  - Common hyperpigmentation disorders in adults: Part I. Diagnostic approach, cafe
      au lait macules, diffuse hyperpigmentation, sun exposure, and phototoxic
      reactions.
AB  - The cause of hyperpigmentation usually is traced to the activity and presence of
      melanocytes. Cafe au lait macules may be solitary benign findings or may indicate
      the presence of neurofibromatosis with its associated complications. Diffuse
      hyperpigmentation should prompt a search for offending medications or systemic
      diseases such as hemochromatosis, hyperthyroidism, and Addison's disease. In
      these instances, the hyperpigmentation may be ameliorated by discontinuing
      offending medications, performing serial phlebotomy in patients with
      hemochromatosis, instituting cause-specific treatments in patients with
      hyperthyroidism, and replacing deficient glucocorticoids and mineralocorticoids
      in patients with Addison's disease. Cosmetic treatment with bleaching agents or
      lasers can be used to decrease pigmentation of ephelides (freckles) and
      lentigines.

PMID- 14655805
TI  - Common hyperpigmentation disorders in adults: Part II. Melanoma, seborrheic
      keratoses, acanthosis nigricans, melasma, diabetic dermopathy, tinea versicolor,
      and postinflammatory hyperpigmentation.
AB  - Nevi, or moles, are localized nevocytic tumors. The American Cancer Society's
      "ABCD" rules are useful for differentiating a benign nevus from malignant
      melanoma. While acanthosis nigricans may signal an underlying malignancy (e.g.,
      gastrointestinal tumor), it more often is associated with insulin resistance
      (type 2 diabetes, polycystic ovary syndrome) or obesity. Melasma is a facial
      hyperpigmentation resulting from the stimulation of melanocytes by endogenous or
      exogenous estrogen. Treatments for melasma include bleaching agents, laser
      therapy, and a new medication that combines hydroquinone, tretinoin, and
      fluocinolone acetonide. Lesions that develop on the shins of patients with
      diabetic dermopathy often resolve spontaneously; no treatment is effective or
      recommended. Tinea versicolor responds to treatment with selenium sulfide shampoo
      and topical or oral antifungal agents. Postinflammatory hyperpigmentation or
      hypopigmentation can occur in persons of any age after trauma, skin irritation,
      or dermatoses.

PMID- 14655807
TI  - Breast cyst aspiration.
AB  - The breast mass is a clinical problem commonly encountered by family physicians.
      Fine-needle and core biopsy techniques require training and cytopathologist
      support. In contrast, breast cyst aspiration using a 21- or 22-gauge needle is a
      simple, cost-effective, minimally invasive procedure. The technique is easy to
      learn and can be practiced on a breast model. Breast cyst aspiration may be
      attempted in many women who present with a palpable, dominant breast mass. If
      clear fluid is aspirated and the mass resolves, malignancy is unlikely, and
      breast cyst is the probable diagnosis. In this situation, reevaluation in four to
      six weeks is appropriate; if the cyst has not recurred, only routine mammographic
      surveillance is required. Referral for fine-needle or excisional biopsy is
      indicated if the aspirate is bloody or extremely tenacious, if no fluid can be
      aspirated, or if there is residual mass after aspiration. Complications such as
      local discomfort, bruising, and infection are uncommon.

PMID- 14655806
TI  - Common problems in patients recovering from chemical dependency.
AB  - Chemical dependency is a common, chronic disease that affects up to 25 percent of
      patients seen in primary care practices. The treatment goal for patients
      recovering from chemical dependency should be to avoid relapse. This requires
      physicians to have an open, nonjudgmental attitude and specific expertise about
      the implications of addiction for other health problems. First-line treatment for
      chemical dependency should be nonpharmacologic, but when medication is necessary,
      physicians should avoid drugs that have the potential for abuse or addiction.
      Medications that sedate or otherwise impair judgment also should be avoided in
      the recovering patient. Psychiatric illnesses should be aggressively treated,
      because untreated symptoms increase the risk of relapse into chemical dependency.
      Selective serotonin reuptake inhibitors may help to lower alcohol consumption in
      depressed patients, and desipramine may help to facilitate abstinence in persons
      addicted to cocaine. If insomnia extends beyond the acute or postacute withdrawal
      period, trazodone may be an effective treatment. If nonpharmacologic management
      of pain is not possible, nonaddictive medications should be used. However, if non
      addictive medications fail, long-acting opiates used under strict supervision may
      be considered. Uncontrolled pain in itself is a relapse risk.

PMID- 14655808
TI  - Information from your family doctor. Breast cyst aspiration.

PMID- 14655809
TI  - The 2001 Bethesda System terminology.
AB  - The 2001 Bethesda System for reporting cervical or vaginal cytologic diagnoses is
      an incremental change in the uniform terminology introduced in 1988 and revised
      in 1991. The 2001 Bethesda System includes specific statements about specimen
      adequacy, general categorization, and interpretation and results. In the adequacy
      category, "satisfactory" and "unsatisfactory" are retained, but "satisfactory but
      limited by" is eliminated. The new category of "atypical squamous cells" (ASC)
      replaces the category of "atypical squamous cells of undetermined significance"
      (ASCUS) and is divided into qualifiers of (1) ASC of "undetermined significance"
      (ASC-US) and (2) "cannot exclude high-grade squamous intraepithelial lesion
      (HSIL)," or (ASC-H). The categories of ASCUS, "favor reactive" and "favor
      neoplasia" are eliminated. The terminology for low-grade squamous intraepithelial
      lesions (LSILs) and HSILs remains unchanged. The category of "atypical glandular
      cells of undetermined significance" (AGUS) is eliminated to avoid confusion with
      ASCUS and is replaced by the term "atypical glandular cells" (AGC), with attempts
      to identify whether the origin of the cells is endometrial, endocervical, or
      unqualified. "Endocervical adenocarcinoma in situ" and "AGC, favor neoplastic"
      are included as separate AGC categories. The presence of normal or abnormal
      endometrial cells is to be reported in women who are at least 40 years of age.
      Educational notes and comments on ancillary testing may be added as appropriate.

PMID- 14655810
TI  - Primary immunodeficiencies.
AB  - Primary immunodeficiencies include a variety of disorders that render patients
      more susceptible to infections. If left untreated, these infections may be fatal.
      The disorders constitute a spectrum of more than 80 innate defects in the body's
      immune system. Primary immunodeficiencies generally are considered to be
      relatively uncommon. There may be as many as 500,000 cases in the United States,
      of which about 50,000 cases are diagnosed each year. Common primary
      immunodeficiencies include disorders of humoral immunity (affecting B-cell
      differentiation or antibody production), T-cell defects and combined B- and T
      cell defects, phagocytic disorders, and complement deficiencies. Major
      indications of these disorders include multiple infections despite aggressive
      treatment, infections with unusual or opportunistic organisms, failure to thrive
      or poor growth, and a positive family history. Early recognition and diagnosis
      can alter the course of primary immunodeficiencies significantly and have a
      positive effect on patient outcome.

PMID- 14655811
TI  - Information from your family doctor. Warning signs of primary immunodeficiency.

PMID- 14655812
TI  - Desloratadine for allergic rhinitis.

PMID- 14655813
TI  - Screening for high blood pressure: recommendations and rationale.

PMID- 14655814
TI  - Violaceous plaques of the face and scalp.

PMID- 14655815
TI  - Information from your family doctor. Ulcers and Helicobacter pylori infection.

PMID- 14655816
TI  - Information from your family doctor. Heartburn.

PMID- 14655817
TI  - Information from your family doctor. Dyspepsia.

PMID- 14655818
TI  - ACOG releases guidelines on cervical cytology screening.

PMID- 14655819
TI  - Root canal disinfection: a review of concepts and recent developments.
AB  - This paper reviews current concepts of root canal infection and the consequences
      for endodontic treatment strategies and practices. In particular, root canal
      disinfection by chemical and mechanical means is discussed, as are the
      possibilities and limitations of proposed methods to reduce the time necessary to
      obtain a disinfected canal.

PMID- 14655820
TI  - Torsional properties of new and used rotary K3 NiTi files.
AB  - The purpose of this study was to compare torque (gcm) and angle of rotation
      (degrees) at fracture of new and used NiTi K3 .04 rotary instruments. The
      relation between size of instrument and torque at fracture was also investigated.
      The torque and angle of rotation at fracture of new and used NiTi K3 .04 rotary
      instruments sizes 15 to 40 were determined according to ANSI/ADA Specification
      No. 28. Analysis of variance was used to compare the torque and angle of rotation
      at fracture among the different sizes of the new instruments and between new and
      used instruments of the same size (alpha = 0.05). The relationship between torque
      at fracture and size of instrument was determined with a regression analysis.
      Torque at fracture of the new instruments increased significantly with the
      diameter (p < 0.05). The used instruments, sizes 25 to 40, had significantly
      lower torque at fracture values compared to the new ones (p < 0.05). The used
      instruments, sizes 20 and 35 had significantly lower angle of rotation at
      fracture compared to the new ones (p < 0.05). A stronger relationship was found
      between the size of the file and the torque at fracture for the new instruments
      (p < 0.0001) compared to the used ones (p < 0.0001). The results of the present
      study suggested that the torque at fracture values of new instruments increased
      significantly with the diameter. The results also suggested that repeated use of
      .04 K3 instruments affected mainly the torque at fracture.

PMID- 14655821
TI  - Inaugural Geoffrey Heithersay oration in endodontics and oral biology.
AB  - Smiles are often a reflection of dental health, and as such provide great
      satisfaction to a dental practitioner who has successfully managed complex dental
      problems such as malformed, malpositioned or traumatically damaged teeth. A
      biological approach to the management of the pulpal and periodontal responses to
      dental trauma has been made possible by cumulative research, and application of
      this knowledge will enhance successful treatment.

PMID- 14655822
TI  - Nickel-titanium rotary instruments: current concepts for preparing the root canal
      system.
AB  - The purpose of this paper is to provide useful information that will enable
      dentists to predictably shape root canals for three-dimensional obturation of the
      root canal system. The information is intended to help clinicians better
      understand when and how to safely use Nickel-Titanium (NiTi) rotary shaping
      instruments. This article is intended to enhance clinical performance for all
      dentists who perform root canal preparation procedures regardless of which
      instruments are chosen and the techniques employed during their utilisation. The
      guidelines for successful access and the concepts and strategies for canal
      preparation are discussed. Additionally, the advantages of negotiating and then
      pre-enlarging the coronal two-thirds of the canal before negotiating and
      finishing the apical one-third are emphasised. Although a set of endodontic
      instruments can shape a root canal, this article will also review the importance
      of irrigants and their role in cleaning the root canal system.

PMID- 14655823
TI  - The past-present-future of endodontics.

PMID- 14655824
TI  - The EAT speaks many languages: review of the use of the EAT in eating disorders
      research.
AB  - The Eating Attitudes Test questionnaire (EAT) has been a major instrument for
      detecting eating morbidity in a great number of studies across the world. The
      instrument was devised by two Canadian research workers and was initially
      validated on a Canadian population. Since then it has been used with reasonable
      success in eating disorders research emanating from English speaking countries,
      particularly the UK. This paper attempts to focus on the application of the EAT
      in non-English speaking countries where it was essential to translate it into the
      language of these countries. Comparative analysis of the results is assessed and
      the degree of success of the instrument in these studies is evaluated. The
      outcome of this review could have significant implications for the future use of
      the EAT in eating disorders research.

PMID- 14655825
TI  - Perceived coping capacity: a comparison between obese patients and patients on
      long-term sick leave.
AB  - Overweight is a significant health problem and perceived by many as a disability.
      While obese persons in the general population are no more likely to suffer from
      mental disorders, many obese individuals experience significant difficulties
      coping with their weight and weight-loss failures. The purpose of this study was
      to investigate the similarities and differences in coping capacity among obese
      and disabled individuals. We compared a group of obese adults (76 consecutive
      obese patients, 82% female) with unemployed long-term sick leave disability
      patients (59 consecutive patients, 46% female) who had an average of 13 +/- 9
      months on disability. We used the Perception of Cognitive Structure, Emotion and
      Control questionnaire (PASEC), which assesses an individual's coping capacity for
      general problems in life and to specific health problems. Both groups
      significantly differed from PASEC normative data, suggesting that they had more
      negative and harmful emotional perceptions of their lives than individuals in the
      normative sample. Compared to long-term sick leave patients' perceptions of
      disabilities, obese patients perceived their weight problems with more negative
      and harmful emotional investment, even after adjustment for gender differences in
      the groups. This suggests that obese patients may experience substantial
      difficulties in coping with their weight problems.

PMID- 14655826
TI  - Lexical decision times for body shape words as a function of dietary restraint.
AB  - Two studies are presented which investigate the relationship between dietary
      restraint and performance on a task in which subjects made lexical decisions for
      body shape and affectively neutral control words. The first experiment found no
      dietary restraint related differences in lexical decision times for body shape
      and neutral words. The second experiment found that, when certain methodological
      problems were controlled for, highly restrained eaters made lexical decisions
      concerning body shape words faster than for affectively neutral words, but did
      not display preferential recall for body shape related words. Further, the second
      experiment found that lexical decision times were significantly related to
      performance on a self-report measure of body shape concern. The results are
      interpreted in terms of current theories on the relationship between cognition
      and emotion.

PMID- 14655827
TI  - Circadian neuroendocrine functions in disorders of eating behavior.
AB  - Eating behavior is a complex function determined by regulatory mechanisms
      characterized by bioperiodic fluctuations. It involves the hypothalamus as well
      as the related higher centers in the central nervous system (CNS). Many hormones,
      neurotransmitters and neuropeptides play an important role in the synchronization
      of food intake. Our study therefore sets out to evaluate the circadian rhythms of
      several endocrine functions in women with eating disorders, to clarify the
      pathophysiology of the limbic-hypothalamic system. We measured the circadian
      rhythms of plasma melatonin, serum cortisol, growth hormone (GH) and prolactin
      (PRL) in 26 patients with anorexia nervosa (AN), 27 with primary obesity (OB) and
      7 with bulimia nervosa (BN). Simultaneous evaluation of different neuroendocrine
      rhythms in these three groups revealed similar circadian abnormalities, (namely
      daytime persistence of melatonin secretion in AN and OB, and similar cortisol
      profile changes in AN and BN), together with evidence of internal
      desynchronization among the different bioperiodic functions. These findings
      suggest that some changes of the central pathways involved in the control of
      eating, mood and endocrine functions are common to dissimilar kinds of eating
      disorders.

PMID- 14655828
TI  - Night eating syndrome in individuals with Mediterranean eating-style.
AB  - Night eating syndrome is identified with no appetite for breakfast, 50% or more
      of food intake after 7 p.m. and trouble getting to sleep and/or staying asleep.
      In a population with a Mediterranean eating style more than 25% of lean healthy
      subjects should be considered as affected by night eating syndrome, thus making
      the definition criteria and even the syndrome itself clinically meaningless.
      Therefore, to assess the presence of night eating syndrome in a population with
      Mediterranean eating and lifestyle, the following definition criteria were
      employed: no food or only a little food for breakfast, sleep disturbances and
      usual consumption of some food just before going to sleep or waking up during
      sleeptime. According to these criteria, 3.5% of lean subjects should be
      considered as affected by night eating syndrome, without any relationship between
      reported psychological distress or tendency to lose control over food intake.
      Further studies in populations with Mediterranean eating style are mandatory to
      assess the true clinical significance of night eating syndrome.

PMID- 14655829
TI  - Diet and exercise in addition to psychotherapy, in the treatment of patients
      suffering from eating disorders with obesity.
AB  - Treating patients with eating disorders is often a controversial issue, and
      obesity adds another difficulty to the treatment regimen. In this study we wanted
      to evaluate the outcome on body weight in patients suffering from eating
      disorders with obesity, by adding dietary treatment and exercise to ongoing
      psychotherapy. The prospective intervention study included 18 obese, female
      patients in primary health care and outpatient clinic with a BMI > or = 27 kg/m2
      with eating disorders, nine of whom were diagnosed with bulimia according to the
      American Psychiatric Association. The patients had had psychotherapy for at least
      2 years in a treatment programme which was chosen by a psychologist. This had had
      no influence on the patients' weight problem, and an additional diet and exercise
      regime was added to the ongoing psychotherapy through an eight-week very low
      calorie diet (VLCD) treatment (Nutrilett), during which the patients also
      participated in weekly group exercise. The patients were followed-up regularly
      during a 6-month period. During the 8-week VLCD treatment, which was completed by
      16 patients (89%), mean body weight in the group decreased significantly from
      98.8 kg to 88.6 kg. Six months after the initial treatment, average weight loss
      was further significantly reduced to 82.5 kg. The findings of the present study
      suggest that by combining ongoing psychotherapy with a well-balanced VLCD
      treatment and exercise it is possible to achieve substantial weight reduction in
      patients suffering from eating disorders with obesity.

PMID- 14655830
TI  - The anorectic effect of increasing doses of L-tryptophan in obese patients.
AB  - Serotonin (5-HT) synthesis in neurons is initiated by hydroxylation of the
      essential amino acid tryptophan. Treatments that raise the level of tryptophan in
      the brain can rapidly alter the rate at which it is converted to 5-HT. This paper
      compares the effect of 1, 2 and 3 g L-tryptophan administered 1 h before a plated
      meal on total food intake and carbohydrate and protein consumption in 10 obese
      subjects (group I) versus a lactose placebo in another 10 obese subjects (group
      II). The mean +/- SD total calorie intakes were: group I, 1188 +/- 94 (1 g); 1031
      +/- 93 (2 g: p < 0.05) and 1016 +/- 85 (3g: p < 0.05); group II: 1294 +/- 62.
      There was a progressive decrease in carbohydrate consumption (expressed as
      available monosaccharide) in function of the tryptophan dose: placebo 131 +/- 8
      g; one g tryptophan 123 +/- 9; two g 114 +/- 13; three g 107 +/- 10. Protein
      consumption was less affected. These results provide further support for the view
      that serotoninergic mechanisms play a role in the regulation of human food
      intake. They are also consistent with the hypothesis that nutrients which
      increase 5-HT availability selectively alter carbohydrate consumption. Further
      studies with modified molecules of naturally occurring tryptophan
      (hydroxytryptophan hydrochloride or diethylpropionate) may offer a potential
      field for the treatment of pathological ingestive behavior.

PMID- 14655831
TI  - Citalopram in anorexia nervosa.
AB  - Thirthy-two female patients who had been diagnosed as having anorexia nervosa
      restricting subtype according to the DSM IV (Diagnostic and Statistical Manual of
      Mental Disorders-IV), were enrolled in a 6-month open trial with citalopram at a
      starting dose of 20 mg. At the end of the trial, 46.9% of the patients showed a
      satisfactory response, 34.4% an unsatisfactory response, improvement criteria
      being weight improvement, menstruation and score reduction on the Symptoms
      Checklist 90R. Anorectics also showed significant improvement in several Eating
      Disorder Inventory-2 (EDI-2) scores at the end of the trial, with greater
      improvement related to satisfactory response to citalopram. Data suggest that
      SSRI (Selective Serotonin Reuptake Inhibitor) Citalopram could be effective at
      least in a subgroup of anorectic patients, both on clinically objective and on
      subjective aspects of anorexia nervosa.

PMID- 14655832
TI  - A setting including psychotherapy and psychopharmacological treatment in a case
      of anorexia nervosa with obsessive compulsive disorder comorbidity.
AB  - In this case report we describe the therapy followed with a patient affected by
      atypical anorexia purging, in a setting that includes both psychotherapy and
      psychopharmacological treatment. The aim of this presentation is to show how the
      patient's ambivalence towards the treatment was faced, and how this work both
      rendered effective the pharmacological therapy and enabled the progression of the
      psychotherapy. There is a discussion of the interaction between psychotherapy and
      pharmacological therapy and their possible beneficial action on the
      symptomatology.

PMID- 14655833
TI  - Sir William Gull (1819-1890). Limner of anorexia nervosa and myxoedema. An
      historical essay and encomium.
AB  - On Friday, October 24, 1873, at a meeting of the Clinical Society of London, Sir
      William Gull achieved a coup de maitre by delivering two seminal reports. The
      first was called, "Anorexia Nervosa, (Apepsia Hysterica, Anorexia Hysterica)".
      The second was entitled, "On a Cretinoid State supervening in Adult Life in
      Women." The manuscript on anorexia was regarded by Gull's peers to be
      significant, but of lesser importance. The essay on hypothyroidism was generally
      regarded to be Gull's chef d'oeuvre. One hundred and twenty-four years later, the
      situation has reversed itself: the anorexia paper is heralded, while the other
      manuscript is all but forgotten. Gull's life, death and contributions will be
      reviewed.

PMID- 14655834
TI  - Prevalence of binge eating disorder in obese adults seeking weight loss
      treatment.
AB  - Binge eating has been identified as a common problem in samples of obese persons.
      Earlier studies found that approximately 30% of participants presenting for
      weight loss treatment could be diagnosed with Binge Eating Disorder (BED). This
      study investigated the prevalence of BED using the Questionnaire on Eating and
      Weight Patterns (QEWP) and the Interview for the Diagnosis of Eating Disorders
      (IDED) in a sample of 468 obese adults seeking weight loss treatment at two
      research facilities. The study found that only a small percentage of the
      participants met Diagnostic and Statistical Manual for Mental Disorders, 4th
      Revision (DSM-IV) diagnostic criteria for BED using either the IDED (1.3%) or
      QEWP (7.3%). A larger percentage of the sample (10.7% based on the IDED and 20.5%
      based on the QEWP) reported binge eating, but did not endorse all criteria
      necessary to warrant a diagnosis of BED. The primary finding of the study was
      that the prevalence of BED in treatment seeking obese adults was much lower than
      was reported in previous studies. Also, there was significant discrepancy in
      prevalence rates of BED as defined by self-report and interview assessment
      methods, with the interview method yielding lower estimates of prevalence. These
      findings suggest that the prevalence of BED may be lower than estimates of
      earlier reports. We recommend that future studies of BED use reliable and valid
      interview methods and that this research focus on more diverse populations,
      including men and a variety of racial and ethnic groups.

PMID- 14655835
TI  - Construction and validation of an anorexia nervosa scale on the MMPI.
AB  - The article describes the construction and validation of an anorexia nervosa
      subscale (ANOR) on the Minnesota Multiphasic Personality Inventory (MMPI). The
      female subjects included 42 anorexic patients, 56 normal controls and 56 patient
      controls. Using an empirical discrimination procedure, 60 items contribute to the
      total homogeneity of the scale and the Chronbach's alpha is 0.86. The five items
      common with the Hysteria scale represent the highest number of common items with
      the main MMPI clinical scales. Crossvalidation findings support the results.
      Content analyses indicate that the ANOR covers important features of anorexia
      nervosa like a fear of sexual matters, disturbed social relations, rigidity, a
      depressed mood, low self esteem and a dissatisfaction with appearance.

PMID- 14655836
TI  - Effects on energy utilization of a beta3-adrenergic agonist in rats fed on a
      cafeteria diet.
AB  - The antiobesity potential of a new beta3-adrenergic agonist (Trecadrine) was
      assessed in a cafeteria model of obesity through body composition, thermogenesis
      and oxygen consumption indicators. Animals fed on a cafeteria diet for 75 days
      increased body weight and fat content, while muscle mass as a percentage of body
      weight was reduced in relation to control fed rats. In addition, in vitro brown
      adipose tissue (BAT) and white adipose tissue (WAT) oxygen consumption was
      increased in these obese animals as compared with controls. Trecadrine
      administration reduced weight gain, BAT and WAT stores as well as the respiratory
      quotient, which was accompanied by an increase in WAT and BAT oxygen consumption
      and rectal temperature. Moreover, muscle mass as a percentage of body weight
      maintained the same values as non-obese animals, while an increase in absolute
      muscle weight was found in Trecadrine-treated obese rats. However, liver weights
      and in vitro oxygen consumption remained unaltered after cafeteria feeding and
      Trecadrine administration. Since chronic administration of Trecadrine had no
      effect on food intake, the stimulation of thermogenesis and oxygen consumption by
      the beta3-adrenergic agonist in white and brown adipose tissue are apparently
      responsible for the rise in energy expenditure as well as for the lower weight
      gain and fat deposition in obese treated rats. Thus, Trecadrine exhibits some
      promise as a potential treatment for obesity.

PMID- 14655837
TI  - Awareness of early-onset anorexia nervosa.
AB  - The aim of the study was to determine whether physicians consider anorexia
      nervosa as a possible diagnosis in children and adolescents presenting various
      somatic symptoms including significant weight loss. Questionnaires were handed
      out to participants of a national general medical congress in Austria. The
      questionnaire included two case vignettes of children with anorexia nervosa and
      questions about diagnosis, differential diagnoses and management. Anorexia
      nervosa was considered as possible primary diagnosis in both cases by 3.8% of the
      respondents and 11.4% suspected a psychosomatic or psychiatric disorder as
      primary diagnosis in both cases. These findings demonstrate a limited awareness
      of anorexia nervosa and of a psychosomatic or psychiatric origin of somatic
      symptoms including weight loss in children and adolescents among physicians.
      Recognizing anorexia nervosa in an early stage and referring the patients for a
      psychiatric evaluation as soon as possible is a prerequisite for specialized
      treatment and might improve the long-term outcome of this severe disorder.
      Increased educational efforts are required to improve the knowledge among primary
      care physicians about eating disorders.

PMID- 14655838
TI  - Psychometric properties of EDE 12.0D in obese adult patients without binge eating
      disorder.
AB  - The aim of the present study is to assess the psychometric properties of the
      Eating Disorder Examination (EDE) 12.0D in obese adult patients without Binge
      Eating Disorder (BED). A consecutive series of 115 obese patients without BED (23
      M; 92 F), seeking treatment for obesity at the Outpatient Clinic of the Section
      of Metabolic Diseases and Diabetology of the University of Florence was studied
      using the EDE 12.0D. Patients had a mean (+/- SD) age of 40.8 +/- 15.1 years, and
      a Body Mass Index (BMI) of 36.3 +/- 5.9 Kg/m2. Internal consistency of EDE and
      its scales was evaluated through Cronbach's alpha; factor structure of EDE 12.0D
      was studied with factor analysis. EDE total and Shape Concern (SC) scores were
      found to be higher in females than in males. EDE total, SC and Eating Concern
      (EC) scores were inversely correlated to age, but not BMI. Factor analysis
      suggested the grouping of items in two subscales. The first scale includes all
      the items from EC, Weight Concern (WC) and SC except reaction to prescribed
      weighing; the second scale consists of all the items from Restraint. Data
      obtained show that items from EC, WC and SC all converge into the same factor
      analysis derived scale in obese patients without BED. EDE 12.0D provides relevant
      information about psychopathological features of obese patients, but a grouping
      of items into subscales different from those originally described could be
      indicated.

PMID- 14655839
TI  - Differential dynamic responses of luteinizing hormone to gonadotropin releasing
      hormone in patients affected by bulimia nervosa-purging versus non-purging type.
AB  - OBJECTIVE: Aim of the study was to investigate the presence of underlying
      abnormalities affecting the hypothalamus-pituitary-gonadal axis in 13 normal
      weight eumenhorreic bulimics as expressed by a different gonadotropin response to
      gonadotropin releasing hormone (GnRH), comparing patients with (n = 6) and
      without (n = 7) purging behaviours to controls (n = 5). METHOD: Subjects were
      administered an intravenous GnRH infusion for four hours, with an additional
      bolus at first and third hour. RESULTS: Non-purging bulimics showed a
      significantly reduced luteinizing hormone (LH) response to GnRH compared to
      controls; purging bulimics, following the second bolus, demonstrated a
      statistically reduced peak, in comparison to both controls and non-purging
      bulimics. DISCUSSION: even in the absence of overt menstrual disturbances, an
      altered LH secretion elicited by pulsatile stimulation of endogenous GnRH was
      found, with a more severe impairment in purging than in non-purging bulimics,
      possibly related to their greater psychopathological and physical burden.

PMID- 14655840
TI  - Family therapy with anorexic-bulimic girls. Beyond systemic rigidity.

PMID- 14655841
TI  - Prepuberal obesity (the adiposogenital syndrome): a transitional object
      pathology.
AB  - The adiposogenital syndrome develops during the puberal period starting from a
      particular family constellation, that is described. The origins of the
      pathological alteration are found at the first object relationships, where
      feeding is felt as self-feeding. Food normally plays the role of transitional
      object in child. In these cases, this role fails and ends by helping separation
      denial. Fat is laid on the intermediate space as a fetish object, a witness of
      the omnipotent fantasy of antistic feeding. The child develops a great ability to
      maintain this balance, making eating a highly pleasant activity. Difficulties
      encountered during treatment are commented.

PMID- 14655842
TI  - Research project on the treatment of anorexia and bulimia: an integrative,
      multidimensional approach.
AB  - This research project tries to test a therapeutic strategy that could improve the
      prognosis of anorexic and bulimic syndrome, by reducing their tendency to
      chronicity. The hypothesis is that, whenever we deal with complex, multifactoral
      syndromes, such as anorexia and bulimia, a therapy based upon the association of
      different kinds of treatments (medical-biological-nutritional treatments plus
      family therapy) helps to obtain better results than one type of treatment only
      (medical-biological-nutritional alone). The selection of the samples
      (experimental and control samples), the materials and methods of the research
      project, and the follow-up series are described.

PMID- 14655843
TI  - Guided self-help of bulimia nervosa in a specialist setting: a pilot study.
AB  - Seventeen patients meeting the DSM-IV criteria for bulimia nervosa were treated
      in a specialist setting according to the "guided self-help" approach as outlined
      in the self-help handbook "Overcoming Binge Eating" by Fairburn. This self-help
      manual is essentially a condensed version of the cognitive-behavioural therapy
      for bulimia nervosa developed by the same author. Every patient took part in 8
      bimonthly sessions each lasting 20 minutes. All subjects were evaluated both
      before and after the treatment through a semi-structured interview. Overall, 10
      patients (58.8%) did well; 6 of these 10 patients (35.3%) stopped binge-eating
      and vomiting altogether. Although the conclusions arising from this pilot study
      have yet to be confirmed by a controlled study, the preliminary findings seem to
      suggest that "guided self-help" in a specialist setting could, indeed, be not
      only sufficient in some cases but may also be the most accessible approach in
      treating many patients affected by bulimia nervosa.

PMID- 14655844
TI  - Leptin and obesity in humans.
AB  - It now appears that leptin is the peripheral signal, hypothesized in the
      lipostasis theory, that informs the central nervous system how much adipose
      tissue there is in the body. The ability of the leptin signal to regulate body
      composition and the amount of body fat has been demonstrated in animals.
      Furthermore, defects in the ob gene and the leptin receptor lead to the
      development of obesity in rodents. No such defects have been found in humans
      although it appears that obese humans are resistant to the action of their
      endogenous leptin. Further characterization of the hormone and ultimately, the
      administration of leptin to humans, will be necessary to determine the role of
      the leptin signal system in the development of obesity in humans.

PMID- 14655845
TI  - Detection of intra- and cross-cultural non-equivalence by simple methods in cross
      cultural research: evidence from a study of eating attitudes in Nigeria and
      Britain.
AB  - The desiderata for cross-cultural research are reviewed showing how this is
      dominated by the presumption of transcultural equivalence hidden by the technical
      problems of translation. This model requires intensive translation work on
      measures to preserve "equivalence". This work can be prohibitively intensive,
      might lead to spurious evidence of "equivalence" and has not produced much
      evidence of equivalence to date. A psychometric axiom--that a measure with low
      reliability cannot have validity--suggests a pragmatic way to explore these
      issues and current statistical software and personal computers make this
      feasible. We recommend that all cross-cultural research should present the
      internal reliability of the data as this will expose all but one theoretical
      problem in the detection of "equivalence". We also suggest that non-equivalence
      may indicate cross-cultural differences in the dimensionality of eating and body
      image concerns rather than just a problem to be exorcised by more translation
      work or to be hidden by not reporting reliability. These issues are not specific
      to work across languages but also apply to comparisons between any social groups
      within cultures. This is shown using data from questionnaires in their original
      English with respondents who were fluent in that language.

PMID- 14655846
TI  - Plasma leptin levels, insulin secretion, clearance and action on glucose
      metabolism in anorexia nervosa.
AB  - From a metabolic point of view, anorexia nervosa may be viewed as a mirror image
      of obesity. We compared insulin secretion, clearance and action on glucose
      metabolism during an intravenous glucose tolerance test in nine women with
      anorexia nervosa and in nine age-matched normal-weight controls. Insulin
      secretion (ISR) was derived by deconvolution of plasma C-peptide levels, insulin
      clearance (MCR(I)) was obtained by dividing the area under the curve (AUC(0-180
      min)) of ISR by the corresponding AUC of plasma insulin levels, insulin
      sensitivity (S(I)) and glucose effectiveness index (S(G)) were calculated by
      Bergman's minimal model. The anorectic women had markedly lower BMI values
      (13.7+/-0.6 vs 23.2+/-0.8 kg/m2, p<0.0001) and serum basal leptin levels (2.8+/
      0.6 vs 8.9+/-1.8 ng/mL, p=0.005) than control women. The anorectic women
      exhibited clear-cut lower fasting and post-glucose plasma insulin levels but
      similar corresponding plasma C-peptide concentrations when compared to controls.
      Consequently, ISR was similar in both groups while MCR(I) was significantly
      increased in anorexia nervosa (MCR(I): 3320+/-881 vs 822+/-79 mL x min(-1) x m(
      2), p<0.02). The index S(I) tended to be higher in anorectic women than in normal
      weight subjects, but without reaching the level of statistical significance
      because of a high between-subject variability (20.2+/-5.7 vs 12.5+/-2.2 10(-5) x
      min(-1)/pmol x L(-1), NS). The index S(G) was similar in both groups (0.022+/
      0.004 vs 0.018+/-0.002 min(-1), NS). In conclusion, low plasma insulin levels
      observed in women with anorexia nervosa result from high MCR(I) rather than from
      depressed insulin secretion. Insulin sensitivity is not systematically increased
      and glucose effectiveness is unchanged in anorectic women when compared to normal
      weight controls.

PMID- 14655847
TI  - Body image in early-onset obese patients.
AB  - In a group of early-onset-obesity obese patients eating behaviour, body image and
      psychological condition were assessed by the Eating Disorder Inventory, the Three
      Factor Eating Questionnaire, the Body Shape Questionnaire and the Body Attitude
      Questionnaire. These evaluations were carried out prior to and at long-term
      follow-up after biliopancreatic diversion when body weight had steadily fallen
      towards normal values. The aim was to establish the influence of actual body
      weight and shape over body image. A notable improvement in eating behaviour and
      overall psychological conditions was observed, while the parameters assessing
      body image remained substantially unchanged, indicating that early-onset-obesity
      postobese subjects, despite having obtained normal or nearly normal weight
      conditions, are still much more dissatisfied with their body weight and somatic
      morphology than never-obese subjects with very similar actual body weights.

PMID- 14655849
TI  - Further experience with the Body Attitude Test.
AB  - The Body Attitude Test (BAT) questionnaire was specifically developed for the
      assessment of patients with eating disorders. To test its usefulness, the BAT was
      administered together with other self-report measures (Body Shape Questionnaire,
      Eating Disorder Inventory, Body Attitude Questionnaire, Rosenberg Self-Esteem
      Scale) in 69 anorectic, 26 bulimic patients and 165 female university students.
      The results indicate that the negative body attitude expressed on the BAT is
      related to other signs of negative body experience. The BAT differentiates
      between clinical and non-clinical subjects and between anorectics and bulimics.

PMID- 14655848
TI  - Cognitive-behavioral therapy versus combined treatment with group psychoeducation
      and fluoxetine in bulimic outpatients.
AB  - A series of 51 female bulimic outpatients, aged 23.4+/-3.9, were assigned either
      to Cognitive-Behavioral Therapy (CBT) or combined Group Psychoeducation and
      Fluoxetine (GPF) treatment. The Eating Disorder Examination (EDE) was performed
      at the beginning of treatment and after 6 months, together with the
      administration of self reported questionnaires for depression (BDI) and Anxiety
      (STAI). A significant (p<0.001) reduction of the number of monthly binge episodes
      (from 25.0+/-12.9 to 6.2+/-3.8 and from 24.8+/-9.1 to 8.0+/-4.3) for CBT and GPF
      respectively were observed. Similar reductions were obtained in the number of
      episodes of compensatory behaviors. Both treatments reduced depression and
      anxiety (p<0.001) while CBT only determined a significative improvement of EDE
      scores. The data obtained suggest that GPF is as effective as CBT in reducing
      bulimic symptomatology but its long-term efficacy should be evaluated in a follow
      up study.

PMID- 14655850
TI  - Professor J.M. Charcot on anorexia.

PMID- 14655852
TI  - Selective processing of eating and body words in restricting-type anorexics,
      binge-eating-type anorexics, bulimics, and control subjects.
AB  - A French adaptation of the Stroop colour-naming task was used to investigate
      selective processing of information related to eating and the body in 92 female
      subjects: 18 with restricting-type anorexia nervosa (RAs), 25 with binge-eating
      type anorexia (BAs), 20 with bulimia nervosa (BNs), and 29 controls (Cs). All
      participants were significantly slower in colour-naming words related to eating
      and the body. This suggests that eating and body Stroop effects were not
      diagnostic category effects. Eating Stroop effect was significantly stronger in
      eating disordered patients than in Cs, but very similar in RAs, BAs, and BNs. It
      did not correlate with the body mass index nor with Eating Disorder Inventory
      (EDI) scores. Body Stroop effect did not differ significantly between groups.
      However some of our results suggested a tendency for this effect to be higher in
      BNs, corroborating previous literature data. Body Stroop effect correlated with
      EDI score in RAs, and with the "body dissatisfaction" subscale score in BNs and
      BAs. It did not correlate with the body mass index. Further studies are currently
      being carried out to determine whether inpatient treatment for anorexia nervosa
      induces significant changes in eating and/or body Stroop effect, and whether such
      changes might be predictive of clinical outcome.

PMID- 14655853
TI  - Clinical and subthreshold eating disorders: case detection in adolescent
      schoolgirls.
AB  - The point prevalence of eating disorders was investigated in schoolgirls from
      lower socio-economic classes and a method of case detection was tested. A two
      stage procedure (self-report measures and interviews) was followed. All girls
      meeting at least one of the following three criteria were recruited as possible
      cases: EAT > or = 30, BMI < 17.5, BMI < 19 or > 24 and EAT > or = 20. The Mann
      Whitney's two-tailed test and the chi-square test were used to assess the
      significance of differences between the possible cases and the others and between
      the false positives and the cases. A diagnosis of eating disorder was made for 24
      subjects (8.1%): 5 (1.7%) with bulimia nervosa and 19 (6.4%) with eating
      disorders not otherwise specified (EDNOS). Of the 24 girls with eating disorders
      only 16 had high EAT40 scores (> or = 30). The other 8 cases were identified by
      the help of other criteria that proved to be useful. Furthermore we found data on
      five self-report instruments (EAT40, EDI, SCANS, SCL90, SEI). On almost all the
      scales, the possible cases obtained scores significantly different from the
      others. On the contrary, we did not find any instrument able to discriminate
      between false positives and cases.

PMID- 14655851
TI  - Factors that may influence future approaches to the eating disorders.
AB  - The past thirty years have seen dramatic changes in our approach to the eating
      disorders. These include marked improvements in the recognition and understanding
      of the disorders, and the reduction of the morbidity and mortality of anorexia
      and bulimia nervosa. Bulimia nervosa itself, now the focus of so much attention,
      was described less than twenty years ago. While these gains, including those in
      the level of knowledge and appreciation by the public, have been transmitted to
      the benefit of patients, there remain significant difficulties in treating people
      with eating disorders. Critical research may address gaps in knowledge and lead
      to more efficacious treatments. At the same time, however, changes in the health
      care system are occurring rapidly and these will have an effect on both research
      and treatment. The purpose of the present article is to highlight scientific and
      systemic factors that the authors feel will play an important role in how people
      with eating disorders are responded to in the coming years. In addressing the
      eating disorders we are confining our remarks to anorexia and bulimia nervosa,
      and not to obesity; the latter would require consideration of many other issues,
      beyond the scope of this review.

PMID- 14655854
TI  - Eating attitudes and prevalence of eating disorders: a survey in secondary
      schools in Lecce, southern Italy.
AB  - Epidemiological studies on eating disorders in southern Italy are practically non
      existent. This study evaluated the eating attitudes and the prevalence of eating
      disorders in a sample of 795 students (588 females and 207 males) among 6
      secondary schools from Lecce. A two-stage study was conducted: a first screening
      stage followed by a clinical interview. 58.4% of girls and 19.7% of boys
      displayed dissatisfaction with regard to their own body. Current dieting was more
      prevalent in girls (18.7%) than in boys (4.8%); 17.9% of normal weight girls and
      11.7% of underweight girls were on a restrictive diet; while only 2.5% of normal
      weight boys were on a diet. Point prevalence rates of eating disorders found in
      our sample were: 0.2% anorexia nervosa, 1.7% bulimia nervosa, and 4% eating
      disorders not otherwise specified category. Although southern Italians are
      stereotypically different from the northern Italians in terms of physical traits,
      historical, cultural and social backgrounds, the prevalence of eating disorders
      in southern Italian adolescent sample is surprisingly similar to those reported
      by the areas of both northern and central Italy as well as other western
      countries.

PMID- 14655855
TI  - The weight gain and ultimate adiposity in cafeteria diet-induced obesity is
      unrelated to the central serotoninergic tonus.
AB  - Early detection of subjects with a propensity to obesity might be of great help
      for setting up preventive intervention studies. In this study we tested whether
      the development of obesity in Wistar rats, given ad libitum cafeteria foods,
      could be predicted by a low prolactin (PRL) response to 5-hydroxytryptophan
      (5HTP), as an index of low hypothalamic serotoninergic tonus. Basal and 5HTP
      stimulated (50 mg/kg body weight i.p.) PRL were measured by RIA in 15 young male
      Wistar rats, whose pelleted diet was afterwards supplemented with cafeteria
      foods. In the tested animals an increase of PRL between 4 and 56 times the basal
      value was observed 60 min after the 5HTP injection. After 2 months of feeding,
      marked inter-individual differences in weight gain between the cafeteria fed
      animals were observed. After 10 months of feeding, median body fat percentage,
      assessed by dual X-ray absorptiometry, of the overfed rats was significantly
      higher than that of control animals: median (range): 41.2% (28.9 - 51.5%) vs 25.1
      (18.0 - 32.2%) (p < 0.0001). The PRL response at the start of the experiment was
      neither correlated with the monthly weight increases, nor with the fat mass
      percentage at the end of the experiment, suggesting that a pre-existing low
      hypothalamic serotoninergic tonus is probably not involved in the overeating and
      ultimate overweight of cafeteria diet fed animals.

PMID- 14655857
TI  - Re-reading Levi-Strauss: "The raw and the cooked" thirty years on.

PMID- 14655856
TI  - Burden and psychiatric symptoms on key relatives of patients with eating
      disorders: a preliminary study.
AB  - Although eating disorders are serious illnesses that affect adolescents and
      strongly involve their families, no study to date investigated the burden of
      these families. Forty relatives of 24 patients with eating disorders were
      assessed on subjective and objective burden, overinvolvement, hypercriticism and
      psychiatric symptoms. The subjective burden reported by the key relatives of
      patients with Anorexia Nervosa was significantly greater than that of the key
      relatives of patients with Bulimia Nervosa. Moreover, the relatives of anorexic
      patients scored higher for overinvolvement and psychiatric symptoms than the
      relatives of bulimic patients. The findings of the present study suggest the
      usefulness of treatment programs that include family counselling.

PMID- 14655858
TI  - A new acellular vascular prosthesis as a scaffold for host tissue regeneration.
AB  - OBJECTIVE: In situ tissue engineering using acellular xenografts is a new
      approach to autologous tissue regeneration. In the present study, we analyzed a
      new regeneration scaffold comprised of xenogenic acellular vessels in a dog
      model. DESIGN OF STUDY AND RESULTS: Xenogenic vascular conduits of porcine
      carotid arteries were acellularized by a 48-hour detergent incubation to extract
      all the cell components of the graft. The acellularisation procedure resulted in
      a complete removal of all cells. After this procedure, heparinization was
      performed sequentially to induce antithrombogenicity in the graft. The burst
      pressure of the graft was tested. The bursting pressure of the fresh vessels was
      2.83 +/- 0.56 x 10(3) mmHg (377 +/- 75kPa, n = 6). After detergent treatment, the
      bursting pressure of the grafts was 2.50 +/- 0.48 x 10(3) mmHg (334 +/- 63 kPa, n
      = 6); after heparinization, it was 3.44 +/- 0.38 x 10(3) mmHg (459 +/- 51 kPa, n
      = 5). In vivo function was tested in a dog model by transplantation to the
      abdominal artery. By 18 weeks, endothelial cells were aligned as in normal,
      healthy artery over the surface of the entire graft. Fibroblasts and macrophages
      had infiltrated the graft from both inside and outside. The neointima contained
      normal layers of smooth muscle cells, which were identified by anti alpha-smooth
      muscle fiber antigen staining. CONCLUSIONS: The acellular heparinized xenograft
      has sufficient mechanical properties and was successfully replaced with host
      tissue, and is thus a promising new type of vascular prosthesis.

PMID- 14655859
TI  - Quantitative assessment of cell viability and apoptosis in cultured epidermal
      autografts: application to burn therapy.
AB  - Cultured epidermal autografts (CEA) have been used in the treatment of burns for
      almost two decades but the clinical results are still inconsistent. In a group of
      37 patients with extensive burn wounds admitted to the University Hospital of
      Lausanne, CEA take ranged between 10 and 100% with a mean of 65%. To investigate
      CEA efficacy in burns, twelve CEA preparations were tested for their biological
      properties with particular emphasis on the balance between cell viability and
      apoptosis. Apoptosis was evaluated by in situ end-labeling (TUNEL), detection of
      DNA fragments in CEA extracts and analysis of caspase-3 activity. All CEA samples
      displayed a high cell viability (> 90%) and a low apoptosis rate (< 6%). However,
      several biological parameters including the activity of transglutaminase showed
      wide interindividual variability suggesting that CEA therapeutic efficacy could
      be partly determined by intrinsic biological factors.

PMID- 14655861
TI  - Building community capacity around chronic disease services through a
      collaborative interorganizational network.
AB  - This article presents the findings of a study examining the evolution of a
      network of health and human service organizations operating in a rural community
      on the Southwest border. The aim of the network was to build the capacity of the
      community to provide chronic disease education, prevention, and treatment
      services by developing collaborative relationships among a broad range of
      organizations. The impetus for the effort was based on receipt of a Turning Point
      grant. The findings, based on two waves of data collected 1 year apart,
      demonstrate how network structure and attitudes toward collaboration evolve as a
      community attempts to build capacity to address its health needs.

PMID- 14655860
TI  - A novel biodegradable PCL film for tendon reconstruction: Achilles tendon defect
      model in rats.
AB  - This study aims to investigate applicability of poly(epsilon-caprolactone) (PCL)
      biodegradable films for repair of gaps in Achilles tendons in a rat model, also
      comparing surgical repair versus no repair approaches. PCL was synthesized with
      tailor-made properties, then, PCL films were prepared by solvent casting. Seventy
      five outbred Sprague-Dawley rats were randomly allocated into five groups: (i)
      sham operated (skin incision only); (ii) no repair (complete division of the
      Achilles tendon and plantaris tendon without repair); (iii) Achilles repair (with
      a modified Kessler type suture); and (iv) plasty of Achilles tendon defects with
      the biodegradable PCL films, and (v) animals subjected to 1 cm mid-substance
      defect with no repair. Functional performance was determined from the
      measurements of hindpaw prints utilizing the Achilles functional index. The
      animals were killed 8 weeks after surgery and histological and biomechanical
      evaluations were made. All groups subjected to Achilles tendon division had a
      significant functional impairment that gradually improved so that by day 28 there
      were no functional impairments in any group whereas animals with a defect
      remained impaired. The magnitude of the biomechanical and morphological changes
      at postoperative 8 weeks were similar for no repair group (conservative),
      Achilles repair group and tendonplasty group (biodegradable PCL film group). The
      initial rate of functional recovery was significantly different for primary
      suture, Achilles repair group and PCL film group (p>0.01). But, at the 28th day,
      functional recovery was quite similar to the other groups. In summary, our
      results suggest that the PCL film can be an alternative biomaterial for tendon
      replacement.

PMID- 14655862
TI  - Exploring contraceptive pill taking among Hispanic women in the United States.
AB  - Data from the 1995 National Survey of Family Growth have previously shown greater
      risk of inconsistent contraceptive pill use among Hispanic women. We used the
      same data to test aculturally based model of pill use among the subsample of
      Hispanic women. Hierarchical logit analyses revealed that primary use of Spanish,
      negative attitudes about women in the workplace, two or more recent sex partners,
      and recent pill adoption were factors that increased the odds of inconsistent
      use. Living alone or with non-kin was associated with more consistent use, as
      were showing preference for a stay-at-home model of motherhood, frequent church
      attendance, and frequent sexual intercourse. Our findings suggest that the strong
      effects of behavioral variables (e.g., duration of pill use, number of sex
      partners) are mediated by cultural indicators (e.g., primary use of Spanish,
      attitudes about sex roles). The extent to which programs address important
      cultural dimensions of health behaviors could enhance effectiveness.

PMID- 14655863
TI  - Illuminating the MPH health educator workforce: results and implications of an
      employer survey.
AB  - The public health workforce has been studied, but not health educators
      specifically. The development of a Master of Public Health (MPH) in community
      health education inspired research to illuminate the San Francisco MPH health
      educator labor market. A time-series survey of an employer panel was conducted
      between 1995 and 1999 regarding the number of MPH health educators on staff,
      hiring projections, and importance of selected competencies. In the San Francisco
      Bay Area, there were 4 MPH health educators per 100,000 persons in 1999. The
      majority worked in local health departments and community-based organizations.
      Although hiring was largely replacement in the late 1990s, employers anticipated
      an increase in hiring from 2000 to 2004. Employers reported that educational
      preparation was adequate, although preparation in specific competencies, such as
      bilingual competence, was lacking. These results suggest a favorable labor market
      for MPH health educators in the San Francisco Bay Area.

PMID- 14655864
TI  - Does graduated licensing empower parents to place greater restrictions on their
      newly licensed teens' driving?
AB  - This investigation sought to determine if Maryland's new graduated licensing
      program was associated with greater levels of parental involvement in, and
      restriction on, teens' unsupervised driving. Separate samples of teens with
      provisional licenses were interviewed by telephone before (n = 424) and after (n
      = 600) the new program took effect. The findings indicated that teens in the new
      program reported significant increases in the frequency of parental driving
      instruction and supervised driving duringthe permit phase. There were no
      differences in amounts of instruction or supervised driving after provisional
      licensure. Also, teens in the new program reported greater overall amounts of
      parental restriction on their driving; however, few specific restrictions showed
      increases. Programs that encourage parents to regulate, restrict, monitor, and
      supervise the driving privileges of their teens during their provisional period
      of licensure are recommended. Graduated licensing laws and programs benefit from
      specific behavioral interventions targeted to, and implemented by, parents.

PMID- 14655865
TI  - The news on health behavior: coverage of diet, activity, and tobacco in local
      newspapers.
AB  - News media are an important and influential part of the social environment,
      calling attention to certain issues by the amount and nature of their coverage.
      To better understand how health behaviors are covered, we examined more than
      80,000 stories in 1,354 newspaper issues from four midsize Missouri communities.
      Health behavior stories were rare. Of 1,373 stories (1.7%) that addressed diet,
      physical activity, or tobacco, few were prominently located in the paper, and
      only half had a primary prevention focus. A large majority had no local angle,
      local quotes, or call to action for individuals or the community, and only 10%
      were generated by local reporters. Because the local newspaper can be especially
      influential in smaller communities, strategies are needed to help reporters and
      editors in these settings provide more and better coverage of health behavior
      related stories.

PMID- 14655866
TI  - The development of a feasible community-specific cardiovascular disease
      prevention program: triangulation of methods and sources.
AB  - Triangulation of methods, sources, and investigators can lead to a
      multidimensional understanding of a particular issue. In this study, the
      combination of qualitative and quantitative data collection methods, and
      information from community and coalition members resulted in the development of a
      tailored community-specific intervention. Three components were triangulated
      after analyzing each separately. A household survey of community members between
      the ages of 25 and 64 years was conducted to identify knowledge, attitudes, and
      behaviors related to cardiovascular disease and to assess risk factor levels.
      Focus group discussions were conducted with community members to describe
      facilitators and barriers to healthy lifestyles, as well as possible
      interventions. Natural group discussions with coalition members analyzed the
      relevance, feasibility, affordability, acceptability, and sustainability of
      specific intervention activities. Results from the different components were
      compared and contrasted. Areas of added information, validation, and
      contradiction were analyzed and guided the development of intervention
      activities.

PMID- 14655867
TI  - Linking perceptions of the community to behavior: are protective social factors
      associated with physical activity?
AB  - Although the relationship of psychosocial factors to physical activity has been
      explored, there is increased interest in how perceptions of the community
      environment influence behavior. However, few methodological studies have
      incorporated perceptions of the social and community environment (protective
      social factors) or addressed key measurement issues. Computer-assisted telephone
      interviews were administered to a national sample of 1,818 U.S. adults.
      Unadjusted and multivariate-adjusted odds ratios were calculated to compare
      active and inactive participants by Protective Social Factors (PSF) scores and
      selected sociodemographics. Confirmatory factor analysis and reliability analysis
      suggested strong PSF scale psychometric properties (alpha = .92). After
      adjustment for potential confounders, a 10-point rise in the PSF score resulted
      in a 12% increased likelihood of meeting Centers for Disease Control and
      Prevention/American College of Sports Medicine recommendations. Additional
      analyses indicated that greater perceived PSFs were associated with meeting these
      recommendations among Whites but not among African Americans.

PMID- 14655868
TI  - A framework for assessing the effectiveness of antihunger advocacy organizations.
AB  - Food insufficiency is a major public health problem that has been linked to poor
      nutritional intake, poor diabetes management, poor cognitive development in
      children, and other adverse health outcomes. Since the 1960s, antihunger advocacy
      organizations (AHAOs) have fought to alleviate hunger at the local, state, and
      federal levels. Few studies have investigated the organizational structure,
      programs, advocacy activities, and outcomes of these organizations, although many
      organizations have been instrumental in advocating for state and federal food
      policy, creating measurements for hunger, and conducting research. Four state
      level AHAOs were studied by using multiple case study methodology and grounded
      theory for analysis to assess organizational effectiveness. The findings
      highlight a conceptual framework that identified 19 important organizational
      characteristics that reflect organizational capacity, performance, achievement,
      and effectiveness. The conceptual framework may be useful in assessing
      effectiveness of public health organizations and coalitions.

PMID- 14655869
TI  - Keeping the focus on public health: the struggles of a tobacco prevention task
      force.
AB  - This case study examines a nonlegislative task force as it struggled to reach
      internal consensus despite external political constraints. The study highlights
      the convergence of politics and science, revealing complex issues likely to be
      confronted by advocates and public health officials. Three themes capture
      participants' experiences: context, sizing up the opportunities and constraints;
      task force process, tacit strategy to operate outside the political context and
      play the science card; and aftermath, a glass half full. The task force took
      advantage of ambiguous parameters, crafting a comprehensive statewide plan to
      reduce tobacco use and breaking out of the common public health paradigm of
      allowing budget considerations to drive program design. These internal victories
      could not sustain a policy success in the legislature. However, the group's
      product sets science-based standards for future program development, and the task
      force's process provides valuable insights into other states developing tobacco
      prevention and control policies.

PMID- 14655870
TI  - The temporal dynamics of the fourteenth-century Black Death: new evidence from
      English ecclesiastical records.
AB  - Recent research has questioned whether the European Black Death of 1347-1351
      could possibly have been caused by the bubonic plague bacillus Yersinia pestis,
      as has been assumed for over a century. Central to the arguments both for and
      against involvement of Y. pestis has been a comparison of the temporal dynamics
      observed in confirmed outbreaks of bubonic plague in early-20th-century India,
      versus those reconstructed for the Black Death from English church records-
      specifically, from lists of institutions (appointments) to vacated benefices
      contained in surviving bishops' registers. This comparison is, however, based on
      a statistical error arising from the fact that most of the bishops' registers
      give only the dates of institution and not the dates of death. Failure to correct
      for a distributed (as opposed to constant) lag time from death to institution has
      made it look as if the Black Death passed slowly through specific localities.
      This error is compounded by a failure to disaggregate the information from the
      bishops' registers to a geographical level that is genuinely comparable to the
      modern data. A sample of 235 deaths from the bishop's register of Coventry and
      Lichfield, the only English register to list both date of death and date of
      institution, shows that the Black Death swept through local areas much more
      rapidly than has previously been thought. This finding is consistent with those
      of earlier studies showing that the Black Death spread too rapidly between
      locales to have been a zoonosis such as bubonic plague. A further analysis of the
      determinants of the lag between death and institution, designed to provide a
      basis for reexamining other bishops' registers that do not provide information on
      date of death, shows that the distribution of lags could vary significantly by
      time and space even during a single epidemic outbreak.

PMID- 14655871
TI  - Human genetic diversity and the nonexistence of biological races.
AB  - Sewall Wright's population structure statistic, F(ST), measured among samples of
      world populations is often 15% or less. This would indicate that 85% of genetic
      variation occurs within groups while only 15% can be attributed to allele
      frequency differences among groups. In this paper, we show that this low value
      reflects strong biases that result from violating hidden assumptions that define
      F(ST). These limitations on F(ST) are demonstrated algebraically and in the
      context of analyzing dinucleotide repeat allele frequencies for a set of eight
      loci genotyped in eight human groups and in chimpanzees. In our analyses,
      estimates of F(ST) fail to identify important variation. For example, when the
      analysis includes only humans, F(ST) = 0.119, but adding the chimpanzees
      increases it only a little, F(ST) = 0.183. By relaxing the underlying statistical
      assumptions, the results for chimpanzees become consistent with common knowledge,
      and we see a richer pattern of human genetic diversity. Some human groups are far
      more diverged than would be implied by standard computations of F(ST), while
      other groups are much less diverged. We discuss the relevance of these findings
      to the application of biological race concepts to humans. Four different race
      concepts are considered: typological, population, taxonomic, and lineage.
      Surprisingly, a great deal of genetic variation within groups is consistent with
      each of these concepts. However, none of the race concepts is compatible with the
      patterns of variation revealed by our analyses.

PMID- 14655872
TI  - Hypoglossal canal size in living hominoids and the evolution of human speech.
AB  - The relative size of the hypoglossal canal has been proposed as a useful
      diagnostic tool for the identification of human-like speech capabilities in the
      hominid fossil record. Relatively large hypoglossal canals (standardized to oral
      cavity size) were observed in humans and assumed to correspond to relatively
      large hypoglossal nerves, the cranial nerve that controls motor function of the
      tongue. It was suggested that the human pattern of tongue motor innervation and
      associated speech potential are very different from those of African apes and
      australopithecines; the modern human condition apparently appeared by the time of
      Middle Pleistocene Homo. A broader interspecific analysis of hypoglossal canal
      size in primates conducted in 1999 has rejected this diagnostic and inferences
      based upon it. In an attempt to resolve these differences of opinion, which we
      believe are based in part on biased size-adjustments and/or unwarranted
      assumptions, a new data set was collected and analyzed from 298 extant hominoid
      skulls, including orangutans, gorillas, chimpanzees, bonobos, siamang, gibbons,
      and modern humans. Data on the absolute size of the hypoglossal nerve itself were
      also gathered from a small sample of humans and chimpanzee cadavers. A scale-free
      index of relative hypoglossal canal size (RHCS) was computed as 100 x
      (hypoglossal canal area(0.5)/oral cavity volume(0.333)). No significant sexual
      dimorphism in RHCS was discovered in any species of living hominoid, but there
      are significant interspecific differences in both absolute and relative sizes of
      the hypoglossal canal. In absolute terms, humans possess significantly larger
      canals than any other species except gorillas, but there is considerable overlap
      with chimpanzees. Humans are also characterized by large values of RHCS, but
      gibbons possess an even larger average mean for this index; siamang and bonobos
      overlap appreciably with humans in RHCS. The value of RHCS in Australopithecus
      afarensis is well within both human and gibbon ranges, as are the indices
      computed for selected representatives of fossil Homo. Furthermore, the size of
      the hypoglossal nerve itself, expressed as the mass of nerve per millimeter of
      length, does not distinguish chimpanzees from modern humans. We conclude,
      therefore, that the relative size of the hypoglossal canal is neither a reliable
      nor sufficient predictor of human-like speech capabilities, and paleoanthropology
      still lacks a quantifiable, morphological diagnostic for when this capability
      finally emerged in the human career.

PMID- 14655873
TI  - The single species hypothesis: truly dead and pushing up bushes, or still
      twitching and ripe for resuscitation?
AB  - Frank Livingstone proclaims himself to be the last living proponent of the single
      species hypothesis. In sharp contrast, a species-rich, bushy phylogeny is favored
      by most human paleontologists. Is Livingstone's proclamation merely contrarian
      posturing, or does closer inspection warrant reconsideration of just how speciose
      the hominin lineage is? The high-speciation perspective draws on evidence of
      speciosity in the Cercopithecoidea and punctuated equilibria theory for support.
      If blue monkeys and redtail monkeys are indistinguishable skeletally, this
      reasoning goes, or if red colobus and black and white colobus are likewise
      indistinguishable, should we not expect that there are more species of hominin
      than is apparent from skeletal evidence alone? A contrarian perspective notes
      that not all monkey taxa are speciose. Importantly, two broadly distributed,
      partly terrestrial monkeys have not speciated at all: vervets and baboons. Nor
      are monkeys the first choice as a hominin speciation model. If expectations of
      species numbers are based on the Hominoidea, a taxon more closely related to
      hominins, more similar in body size, and found in more hominin-like habitats than
      monkeys, a single-species perspective is more appealing. No great ape genus has
      even two sympatric species. Moreover, despite a separation of 1.6 Ma, West
      African chimpanzees have not speciated from Pt. troglodytes nor Pt.
      schweinfurthii. It is notable that no two contemporaneous species of hominin were
      separated by significantly more than this interval. A biological--as opposed to
      an ecological or geographical--species definition would place all hominins in a
      single, phenotypically diverse species. Since divergence from the chimpanzee,
      "species" distinctness in hominins may have been maintained by temporary
      allopatry and centripetal niche separation. The hominin lineage may have evolved
      as a single, phenotypically diverse, reticulately evolving species.

PMID- 14655874
TI  - Down syndrome: interaction between culture, demography, and biology in
      determining the prevalence of a genetic trait.
AB  - The incidence of Down syndrome (DS) at conception is highly dependent upon the
      maternal age distribution and age-specific pregnancy rates. Live-birth prevalence
      of DS reflects these factors and fetal deaths. Since the introduction of prenatal
      diagnosis in the early 1970s, the role of fetal deaths in the equation has
      increased. Between 1920 and the early 1980s, DS live-birth prevalence decreased
      in many populations due to declining fertility rates, particularly among older
      women. In the late-1970s the trend reversed, as the median age of populations and
      birth rates among older women steadily increased. This paper illustrates these
      interactions using data we have analyzed for New York State (NYS) and comparative
      data obtained from the literature. Between 1983 and 1997 DS live-birth prevalence
      in NYS remained stable at about 9.9 per 10,000 live births. The number of
      prenatal tests performed increased by 158%, and the number of DS fetuses detected
      prenatally more than quadrupled. Fertility rates of women aged 35-49 continued to
      increase. The proportion of DS cases born to these older mothers increased from
      23% in 1985 to 43% in 1997. We estimated that without prenatal diagnosis, DS live
      birth prevalence would have been 17.0 per 10,000 live births by 1995. Cultural
      factors influence demographic trends, birthing technologies, physician practices,
      and women's decision-making regarding prenatal screening and diagnosis for DS.

PMID- 14655875
TI  - The evolution of human phenotypic plasticity: age and nutritional status at
      maturity.
AB  - Several evolutionary optimal models of human plasticity in age and nutritional
      status at reproductive maturation are proposed and their dynamics examined. These
      models differ from previously published models because fertility is not assumed
      to be a function of body size or nutritional status. Further, the models are
      based on explicitly human demographic patterns, that is, model human life-tables,
      model human fertility tables, and, a nutrient flow-based model of maternal
      nutritional status. Infant survival (instead of fertility as in previous models)
      is assumed to be a function of maternal nutritional status. Two basic models are
      examined. In the first the cost of reproduction is assumed to be a constant
      proportion of total nutrient flow. In the second the cost of reproduction is
      constant for each birth. The constant proportion model predicts a negative slope
      of age and nutritional status at maturation. The constant cost per birth model
      predicts a positive slope of age and nutritional status at maturation. Either
      model can account for the secular decline in menarche observed over the last
      several centuries in Europe. A search of the growth literature failed to find
      definitive empirical documentation of human phenotypic plasticity in age and
      nutritional status at maturation. Most research strategies confound genetics with
      phenotypic plasticity. The one study that reports secular trends suggests a
      marginally insignificant, but positive slope. This view tends to support the
      constant cost per birth model.

PMID- 14655876
TI  - A number no greater than the sum of its parts: the use and abuse of heritability.
AB  - Though widely used in quantitative genetics, in the study of human variation
      perhaps no statistic is more easily misinterpreted than heritability. While the
      contribution of genetic heritage to complex biological and behavioral phenotypes
      cannot be lightly dismissed, nonetheless we remain profoundly ignorant of how
      that legacy plays out in any environmental context. To be sure, it is not
      reducible to a single number. Nor does the preference among anthropologists for
      analyzing biological rather than behavioral phenotypes improve what heritability
      can reasonably say about the sources of human variation. This paper discusses the
      meaning of heritability, the methods for its estimation, the fallacies underlying
      its misuse, and its utility for inquiries in evolutionary anthropology and
      epidemiology. Progress in anthropological genetics will be realized through
      greater sophistication in study designs, including the measurement of
      environmental (physical and sociocultural) variation and the judicious choice of
      phenotypes for study. Elucidating the ontogenetic processes underlying adaptive
      plasticity is particularly critical to understanding the evolution of human
      biological variation. Such advancements will also shed light on the feasibility
      of genotype-targeted biomedical treatments. Failure to appreciate the limits of
      such approaches can divert resources from demonstrably effective environmentally
      based health interventions that benefit entire populations. Simplistic notions of
      genetic determinism should be challenged for the sake of our theories and the
      well-being of larger communities. As exemplified by the work of Frank B.
      Livingstone, anthropological genetics is at its best when incorporating
      anthropology into the study of human phenotypic variation.

PMID- 14655877
TI  - Polymorphisms past and present.
AB  - Polymorphisms, particularly genetic variants of the red blood cell, have served
      as a major focus for the research of Frank B. Livingstone over the course of a
      long and productive career. Recent investigations confirm the value of key
      insights that he contributed to this area more than four decades ago. As
      Livingstone recognized, the same underlying evolutionary model that guides
      genetic studies in present populations also provides a productive framework for
      interpreting patterns of variation in the skeleton and dentition throughout past
      human evolution. Examples explored in detail here include polymorphisms in
      hominoid nasal bone shapes and fourth lower premolar roots. This work provides
      both empirical and theoretical contexts for investigating patterns of human
      variation over the last 6 to 8 million years.

PMID- 14655878
TI  - The mind of primitive anthropologists: hemoglobin and HLA, patterns of molecular
      evolution.
AB  - Frank Livingstone played a central role in defining the population genetics of
      the sickle cell mutation at position 6 of the human beta globin gene, the most
      famous amino acid substitution in evolutionary biology. Its discovery occurred at
      a time when traditional, 19th-century principles of natural selection were being
      joined with the newly discovered mechanics of DNA structure and protein synthesis
      to produce Neo-Darwinian theory. When combined with the epidemiology of malaria
      in Africa, differential mortality for both homozygotes, and the resulting
      advantage of the heterozygote, sickle cell became the classic balanced
      polymorphism. Human HLA-A has 237 molecular alleles. The histocompatibility
      system has as its primary function the presentation of peptides to T-cell
      receptors and plays an essential role in the immune system. Nearly all of the
      alleles are codominant and fully functional. Despite almost 30 years of disease
      association studies with HLA-A, no convincing evidence has been found for
      differential fertility or mortality at this locus. Yet the dogma in the
      histocompatibility field is that this extensive human polymorphism is maintained
      by "balancing selection." Explaining HLA-A polymorphism is what one might call
      the sickle-cell-effect. This one mutation, coming as it did at the historical
      convergence of Darwinian theory and modern genetics, and carrying with it the
      strong relationship between mutation, disease, and allele frequency, has
      conditioned our discussion of human genetic variation and population genetics.
      Has the strength of this early idea made evolutionary biologists uncritical of
      systems like HLA-A and retarded the search for new mechanisms of molecular
      evolution? Is it now time to move away from a focus on mutation and polymorphism
      in evolutionary genetics and toward a systems theory that would explain the
      origin and evolution of hemoglobin and HLA-A and the biochemical pathways that
      surround them?

PMID- 14655879
TI  - Testing the "malaria hypothesis" for the case of Thailand: a genetic appraisal.
AB  - This study provides statistical analyses of allele frequencies for populations of
      Thailand, with an attempt to trace the roles of differential malarial selection
      and genetic admixtures on the observed frequency variation of certain red cell
      genetic abnormalities (the two beta-globin variants--hemoglobin E and beta
      thalassemia--and G-6PD deficiency), probably evolving under malarial endemicity.
      It is found that frequencies of hemoglobin E vary accordingly with those of G-6PD
      deficiency, and with diverse malarial ecology. The levels of genetic diversity
      are greater for hemoglobin E and G-6PD deficiency than for most other nonmalarial
      related genetic markers, suggesting the evolution of these two genetic
      abnormalities under differential selection. Results of the Mantel's statistical
      test for correspondence between distance matrices suggest distinctive patterns of
      allele frequency differentiation between malarial-related and nonmalarial-related
      genetic loci. Correlations between beta-globin and G-6PD genetic distances, as
      well as those between both sets of distances and the malarial distances, are
      statistically significant. On the other hand, a correlation between malarial
      distances and the genetic distances for nonmalarial-related genetic loci is not
      significant statistically. A correlation between the beta-globin genetic
      distances and the genetic distances for nonmalarial-related genetic loci is,
      however, statistically significant. The latter result could be attributed largely
      to the clustering of relatively high hemoglobin E frequencies among genetically
      closely related populations of northeastern Thailand, whose recent homeland was
      Laos. The consistently low frequencies of beta-thalassemia observed in most
      studied populations are explained as a result of the replacement of this genetic
      variant by hemoglobin E, under long-term malarial selection.

PMID- 14655880
TI  - Simulating hemoglobin history.
AB  - In one of the truly classic works in anthropological genetics, Frank Livingstone
      established the interrelationships between agriculture, mosquito ecology,
      malaria, and, consequently, the frequencies of sickle cell hemoglobin in West
      Africa. A major inference from Livingstone's study was the recency of malaria as
      a selective agent in human populations, only becoming significant after the
      adoption of agriculture in the last few thousand years. Clines of the abnormal
      hemoglobin alleles might therefore represent continuing waves of advance of
      adaptive alleles. In order to model the complex interaction of several hemoglobin
      alleles, selection, and gene flow spreading adaptive mutants, Livingstone turned
      to computer simulation. Numerous insights concerning the competitive increase of
      different alleles (hemoglobins S, C, and E and thalassemia), the rate of allele
      spread under different migration scenarios, including the potential importance of
      long-range migration, came out of these studies. These experiments also
      stimulated others to search for mechanisms that might increase the diffusion rate
      of hemoglobin variants, including kin-structured migration and epidemic disease
      selection. Recent molecular studies have substantiated major aspects of
      Livingstone's work (including the recent origin of falciparum malaria) and posed
      challenges to some of his assumptions (such as the number of mutations to
      hemoglobins S and E). But whatever the fate of his specific hypotheses, his
      emphasis on the interaction of genetics, ecology, and culture stands as a model
      for the anthropological approach to the understanding of human variation and
      evolution.

PMID- 14655881
TI  - Anthropology at the University of Michigan in the late 1950s.
AB  - By 1958, the Anthropology Department at the University of Michigan had emerged as
      a major center in the discipline. Its excellence derived from a strong faculty,
      commitment to an integrated view of the field, and broader support from a rising
      national tide of scholarship. While many new intellectual currents developed,
      among the strongest was biological-behavioral theory--somewhat ironically
      flourishing in a biological anthropology program that viewed itself as a nexus of
      population genetics. The biological anthropology faculty thought like
      anthropologists. From this environment, Frank Livingstone not only drew
      intellectual support, but also became a key player in demonstrating the
      importance of historical and cultural factors to shaping biological patterns. A
      biocultural perspective is evident in Michigan research to this day.

PMID- 14655883
TI  - Jargon, eponyms, and just plain obfuscation.

PMID- 14655882
TI  - THINK! Being a student of Frank B. Livingstone.

PMID- 14655884
TI  - Osteochondral autografts for osteochondritis dissecans of the talus.
AB  - Eighteen symptomatic advanced-stage osteochondritis dissecans (OCD) of the talus
      (Berndt and Harty stages III 7 and IV 11) in 17 patients were treated with
      multiple autogenous osteochondral cylindrical grafts. The mean time of follow-up
      was 36 months (range, 25-49). The average age at surgery was 22.7 years (range,
      19-34). The mean size of defect of OCD was 13.6 mm x 7.2 mm. Two or three
      osteochondral grafts (6 or 7 mm in diameter and 15-20 mm in length) were
      harvested from the superomedial margin of the ipsilateral knee. A partial
      osteotomy of the medial malleolus or osteotomy of the distal lateral tibia was
      performed for all cases. Being evaluated by the Freiburg ankle score, 16 of 18
      ankles (88.8%) had excellent and two (11.8%) had good results. "Second-look"
      arthroscopy of 16 ankles revealed consistency of the osteochondral grafts and
      congruity between grafts and native cartilage in 14 (87.5%), and a softening or
      fissuring of the osteochondral graft in two. Our results showed that this
      procedure provided an effective treatment for a symptomatic advanced-stage OCD of
      the talus.

PMID- 14655885
TI  - Extracorporeal shock wave therapy (ESWT) in patients with chronic proximal
      plantar fasciitis: a 2-year follow-up.
AB  - The aim of this study was to compare the effect of extracorporeal shock wave
      therapy (ESWT) in patients with chronically painful proximal plantar fasciitis
      with a further conventional conservative treatment. Forty-seven patients (49
      feet) with a previously unsuccessful nonsurgical treatment of at least 6 months
      were randomized to two groups. Heel cups had to be worn throughout the study.
      Group 1 (25 heels) was treated immediately with three sessions of ESWT (3000
      shock waves/session of 0.2 mJ/mm2) at weekly intervals. The patients of group 2
      (24 heels) continued nonsurgical treatment (iontophoresis with diclofenac and an
      oral nonsteroidal anti-inflammatory drug) for 12 weeks. After this period they
      were treated using the protocol of group 1. No significant difference of pain and
      walking time after further nonsurgical treatment (3 months) was seen in group 2.
      At 12 weeks after ESWT, the pain estimation on the visual analogue scale (VAS)
      for activities of daily living diminished significantly by 62.9% in group 1 and
      by 63.0% in group 2. The comfortable walking time had increased significantly in
      both groups. Two years after ESWT, pain during activities of daily living
      decreased by 94% in group 1 and by 90% in group 2 on the VAS and the comfortable
      walking time had increased significantly in both groups.

PMID- 14655886
TI  - Acute surgical management of Jones' fractures.
AB  - The purpose of this study was to evaluate the effectiveness of surgical
      management for acute Jones' fractures and Torg types I and II proximal diaphyseal
      stress fractures presenting acutely in both athletes and nonathletes. Twenty-two
      patients underwent intramedullary screw fixation between 1994 and 1999. Immediate
      intramedullary screw fixation of acute Jones' fractures and type I stress
      fractures resulted in a 100% union rate with an average time to union of 6.2
      weeks. Fixation of type II stress fractures had a union rate of 100% with a mean
      time to union of 8.3 weeks. The overall complication rate was 9%. Surgical
      intervention allowed an earlier return to weight-bearing with a more rapid and
      predictable union rate. The authors recommend intramedullary fixation as a
      treatment of choice for the management of fifth metatarsal fractures distal to
      the tuberosity in nonathletes as well as athletes.

PMID- 14655887
TI  - Bunionette deformity correction with distal chevron osteotomy and single
      absorbable pin fixation.
AB  - Between January 1997 and July 2000, 10 patients with symptomatic bunionette
      deformity underwent 12 distal fifth metatarsal chevron osteotomies in which an
      absorbable poly-p-dioxanone suture (PDS) pin was used for fixation. Of the 10
      patients, nine were female. Average age at operation was 41 years (range, 23-70).
      Mean duration of follow-up was 48 months (range, 6-81). All patients obtained
      clinical and radiographic union by 6 weeks, and there was no radiographic
      evidence of osteolysis, displacement, or avascular necrosis of the metatarsal
      head at final follow-up. There were no serious complications. The average
      postoperative AOFAS score was 93 of 100 possible. All patients were satisfied
      with the procedure and would have it again. Distal chevron osteotomy with a
      single, nonpredrilled PDS absorbable pin for the correction of symptomatic
      bunionette deformity is a reliable and effective technique that provides adequate
      fixation without complications.

PMID- 14655888
TI  - A protocol for treatment of unstable ankle fractures using transarticular
      fixation in patients with diabetes mellitus and loss of protective sensibility.
AB  - BACKGROUND: Surgical treatment of ankle fractures in patients with diabetes
      mellitus is associated with a high complication rate. Diabetic patients with
      peripheral neuropathy are a particularly difficult group to treat because of
      their inability to sense deep infection, repeat trauma, and wound complications.
      The purpose of this study was to evaluate a protocol that included transarticular
      fixation and prolonged, protected weightbearing in the treatment of unstable
      ankle fractures in diabetic patients with peripheral neuropathy and loss of
      protective sensibility. METHODS: The authors retrospectively reviewed the records
      of 15 patients with diabetes mellitus, unstable ankle fractures (AO
      classification 44B), and loss of protective sensibility confirmed via testing
      with a 5.07 Semmes-Weinstein monofilament. Retrograde transcalcaneal-talar-tibial
      fixation using large Steinmann pins or screws in conjunction with standard
      techniques of open reduction and internal fixation was used. The postoperative
      treatment protocol included: 1) short leg, total contact casting and
      nonweightbearing status for 12 weeks; 2) removal of the intramedullary implants
      between 12 and 16 weeks; 3) application of a walker boot or short leg cast with
      partial weightbearing for an additional 12 weeks; and 4) transition to a custom
      molded ankle-foot orthosis (AFO) or custom total-contact inserts in appropriate
      diabetic footwear. RESULTS: The major complication rate for all fractures was 25%
      (4/16) and for closed fractures was 23% (3/13). These are lower than previously
      reported rates between 30% (3/10) and 43% (9/21) for diabetic patients with and
      without neuropathy. The amputation rate for all fractures was 13% (2/16) and for
      closed fractures alone was 8% (1/13). These are similar to previously reported
      rates of 10% (2/10) to 20% (2/21). There were no deaths or Charcot malunions in
      this series. The combination of transarticular fixation and prolonged, protected
      weightbearing provided 13 of 15 patients with a stable ankle for weightbearing.
      CONCLUSION: Although these fractures remain a treatment challenge, this study
      presents a successful, multidisciplinary protocol for treatment of unstable ankle
      fractures in the most challenging group of diabetic patients - those with loss of
      protective sensibility.

PMID- 14655889
TI  - Biomechanical differences among pes cavus, neutrally aligned, and pes planus feet
      in subjects with diabetes.
AB  - The purpose of this study was to quantify differences in joint range of motion,
      foot deformity, and foot morphology among pes cavus, neutrally aligned, pes
      planus rigid, and pes planus flexible feet. A cohort of 1047 veterans with
      diabetes (contributing 2047 feet) was enrolled in a prospective study of diabetic
      ulcer risk factors (the Seattle Diabetic Foot Study). Significant differences
      between foot types were found. Pes cavus feet had an increased percentage of
      prominent metatarsal heads, bony prominences, and hammer/claw toes (p < .0001),
      as well as significantly increased amounts of hallux dorsiflexion and decreased
      amounts of hallux plantarflexion (p < .0001) with a total range of motion equal
      to the other foot types (p = .3). Neutrally aligned feet had a lower percentage
      of intrinsic muscle atrophy, bony prominences, and hammer/claw toes (p < .0001).
      Pes planus feet had an increased lateral talometatarsal angle (p < .0001) and an
      increased second metatarsal length. These data demonstrate structural differences
      between foot types in a population with diabetes.

PMID- 14655890
TI  - Optical plantar pressure analysis following internal fixation for displaced intra
      articular os calcis fractures.
AB  - Using optical pedobarography, the outcome of open reduction and internal fixation
      of displaced os calcis fractures was assessed. In 12 patients, well reconstructed
      heel contact widths and no reduction in heel-ground contact times were found. In
      conjunction with this, patients showed lateral deviation of the plantar pressures
      and load bearing, indicating that subtalar and calcaneocuboid joint function
      remained altered despite reconstruction. These findings could not be linked to
      the initial fracture severity or clinical outcome score.

PMID- 14655891
TI  - Strength analysis and comparison of the Teno Fix Tendon Repair System with the
      two-strand modified Kessler repair in the Achilles tendon.
AB  - BACKGROUND: Various options exist for repair of Achilles tendon ruptures, yet a
      method that consistently provides sufficient gap resistance to allow early
      mobilization remains elusive. This study compares the mechanical performance of a
      modified Kessler repair with that of the Teno Fix Tendon Repair System (Ortheon
      Medical, LLC) in matched pairs of cadaver Achilles tendons. METHODS: The two
      strand modified Kessler repair was selected as the control construct on the basis
      of literature review and physician interviews which identified it among the many
      options as a popular method for repair of acutely ruptured Achilles tendons. Test
      specimens were harvested from matched pairs of cadaver ankles. The tendons were
      transected 3.5 cm proximal to the calcaneal insertion and repaired with either
      the two-strand modified Kessler suture construct or the Teno Fix Tendon Repair
      System. Assignment to the modified Kessler or Teno Fix group was done randomly
      for the first member of each pair. All test and control repairs were performed by
      the same author to reduce variability. Evaluation of the repairs consisted of
      tensile strength testing and measurement of the gap formation and peak stresses.
      RESULTS: Gap and peak stress for the two-strand modified Kessler repair were 0.30
      +/- 0.15 N/mm2 and 1.03 +/- 0.51 N/mm2, respectively. For the Teno Fix repairs
      the mean gap and peak stress values were 0.80 +/- 0.46 N/mm2 and 1.19 +/- 0.12
      N/mm2, respectively. The mean gap formation stress was significantly higher in
      the Teno Fix repairs than in the control repairs (p < .0005). There was no
      significant difference in peak strength between the repairs (p < .10).
      CONCLUSIONS: The Teno Fix repair was superior to the modified Kessler repair. In
      the Teno Fix repairs, the gap formation stress was 67% of the peak tensile
      stress. In comparison, in the modified Kessler repairs, the gap formation stress
      was 29% of the peak stress. This can be correlated to the elastic property of the
      modified Kessler suture and the initial tightening of the suture around the
      tendon fibers. The Teno Fix system is nonelastic and is fully tensioned during
      installation. This lends to a more gap resistant repair.

PMID- 14655892
TI  - A feasibility trial of a prefabricated immediate postoperative prosthetic limb
      system.
AB  - In this feasibility trial, 32 consecutive patients undergoing transtibial or knee
      disarticulation amputation had application of a prefabricated immediate
      postoperative prosthesis in the operating room following lower extremity
      amputation. Partial weightbearing was initiated on the first postoperative day.
      Twenty-nine underwent primary amputation as a consequence of nonsalvageable
      gangrene or diabetic foot infection. Others were performed at the time of wound
      closure following traumatic amputation for a crushed extremity and one was
      performed for an infected nonunion of the tibia and fibula. Seventeen of the 29
      patients with diabetes were insulin dependent. Nine patients required renal
      dialysis and were diagnosed with concurrent malnutrition. Twenty were male and 12
      were female, with an average age of 61.6 (range, 42-90) years. The average time
      to custom prosthetic limb fitting was 8.1 (range, 4-16) weeks. This preliminary
      experience with a commercially available pneumatic immediate postoperative
      prosthetic limb system supports its role in the early rehabilitation of lower
      extremity amputees.

PMID- 14655893
TI  - Primary synovial chondromatosis of the subtalar joint affecting two brothers.
AB  - Primary synovial chondromatosis is a rare benign condition characterized by the
      formation of multiple cartilaginous nodules in the synovium of joints and on
      occasions tendon sheaths or bursae. A case of primary synovial chondromatosis
      affecting the subtalar joint is reported. The patient's brother developed the
      same condition affecting the same joint 2 years later. The proposed etiologies
      are discussed including the presence of the proto-oncogene C-erb B-2.

PMID- 14655894
TI  - Giant cell tumor of the tendon sheath of the toe imitating macrodactyly: case
      report.
AB  - The authors present a case of giant cell tumor of the tendon sheath (GCTTS)
      imitating macrodactyly macroscopically. They give an overview of the differential
      diagnosis of macrodactyly, the behavior of GCTTS, its most frequent
      localizations, the scope of surgical procedures available in cases of the
      disproportionate enlargement of a digit, and also of earlier GCTTS cases recorded
      in the files of the Orthopedic Clinic of the Semmelweis University.

PMID- 14655895
TI  - Intravascular papillary endothelial hyperplasia: a pseudotumor presenting on the
      plantar foot.

PMID- 14655896
TI  - Technique tip: using cannulated drills to place solid screws.

PMID- 14655897
TI  - Technique tip: fixation of dorsal wedge osteotomy for Freiberg's disease using
      bioabsorbable pins.

PMID- 14655898
TI  - Genetic factors and asthma in aluminum smelter workers.
AB  - An asthma-like condition has been reported among aluminum smelter potroom
      workers. The pathophysiologic mechanisms and the causative agent involved are
      unknown. Inasmuch as gene polymorphisms are associated with asthma in the general
      population, the authors of this case-control study examined whether polymorphisms
      were associated with the development of potroom asthma. Genotyping was performed
      for the beta2-adrenoreceptor, high-affinity Ig (immunoglobulin) E receptor, and
      Tumor Necrosis Factor on potroom workers who developed a new asthma-like
      condition and on individuals who did not develop respiratory problems. No
      associations were found between potroom asthma case status and genotype. The
      asthma-like condition associated with potroom work remains poorly understood.
      Future investigations of genetic susceptibility and occupational asthma may
      provide pathophysiologic insights into these work-related conditions, but larger
      numbers of subjects will be required.

PMID- 14655899
TI  - Particulate air pollution and chronic respiratory symptoms among traffic
      policemen in Bangkok.
AB  - In this cross-sectional study, the authors examined the relationship between
      traffic-based air pollution and chronic, nonspecific respiratory symptoms among
      traffic policemen in Bangkok, Thailand. A total of 1,603 policemen who lived and
      worked in areas that had 3 different levels of airborne particulates were
      evaluated. The authors used a modified standardized questionnaire to identify
      nonspecific respiratory disease (NSRD) in participants. The prevalence of NSRD in
      heavily polluted, moderately polluted, and suburban areas was 13.0%, 10.9%, and
      9.4%, respectively. Among nonsmokers, the age-adjusted prevalence of NSRD in the
      heavily polluted areas was significantly higher than in the suburban control
      area. Also among nonsmokers, the odds ratio for NSRD for each 10-microg/m3
      increase in ambient particulate matter was 1.11. The authors concluded that the
      increased prevalence of respiratory symptoms among traffic policemen in Bangkok
      was associated with urban traffic air pollution.

PMID- 14655900
TI  - Dose-related cognitive deficits among floor layers with previous heavy exposure
      to solvents.
AB  - The authors used tests of attention and memory, which are sensitive to the
      influence of aging, to explore possible adverse effects on cognitive functioning
      following past heavy exposure to solvent-based glues, with special reference to
      dose-effect relationships and interactions with the aging process. The study
      included 41 floor layers and 40 carpenters (referents) who participated in a
      longitudinal follow-up assessment. The authors assessed cognitive functioning
      with the following tests: trail-making, color words, and word recall. Higher
      cumulative exposure was associated with poorer test performance that was related
      to concept shifting, episodic memory, and speed of congruent and incongruent
      color naming. The magnitude of the decrements in memory tasks was equivalent to
      about 20 yr of age-related decline. Dose-effect relationships were seen mainly
      for contact adhesives, and there was partial evidence for an interaction between
      exposure and aging.

PMID- 14655901
TI  - Total cadmium intake and mortality among residents in the Jinzu River Basin,
      Japan.
AB  - This study investigated the relationship between total cadmium intake and
      mortality among rural inhabitants of the Jinzu River Basin, Japan. A follow-up
      survey was conducted for 6,128 days on 3,236 inhabitants. The rural communities
      were divided into 2 groups, one with a total cadmium intake of < 2.0 gm and the
      other > or = 2.0 gm. Standardized mortality ratios and a Cox's proportional
      hazard model indicated mortality risk was greater in the > or = 2.0 gm group,
      compared with the < 2.0 gm group. In the Jinzu River Basin, a total cadmium
      intake > or = 2.0 gm exerts an adverse influence on life prognosis.

PMID- 14655903
TI  - Pleural mesothelioma cases in Biancavilla are related to a new fluoro-edenite
      fibrous amphibole.
AB  - A cluster of deaths from pleural mesothelioma was previously reported for
      Biancavilla, Italy, a city in eastern Sicily. An environmental survey suggested
      that the stone quarries located southeast of the city might be a source of
      asbestos exposure. The materials extracted from the quarries, used widely in the
      local building industry, contain large quantities of a fibrous amphibole that was
      initially referred to as an anomalous intermediate phase of sodium- and fluorine
      rich tremolite-actinolite. A subsequent crystal chemistry investigation
      identified the mineral as fluoro-edenite, a new end-member of the edenite -->
      fluoro-edenite series. The material is very similar in morphology and composition
      to the minerals of the tremolite-actinolite series. To the authors' knowledge,
      fluoro-edenite becomes the 3rd mineral fiber (along with erionite and winchite),
      not yet classified as asbestos, with a demonstrable mesotheliomatogenous action
      in humans.

PMID- 14655902
TI  - Pesticide use among farmers in the Amazon basin of Ecuador.
AB  - Pesticide use is one of the most significant occupational exposures for
      agricultural workers in the Amazon basin of Ecuador. A structured questionnaire
      was developed focusing on sociodemographic characteristics, knowledge and
      experience of adverse health effects related to pesticide use, details of work
      practices, and an inventory of pesticides used on the farm. Of the 112 farmers
      interviewed, 111 (99.1%) used pesticides. Paraquat was most commonly used
      (77.4%), followed by glyphosate (65.7%). Respondents had good knowledge about the
      acute health effects of pesticides and their exposure routes. Risk behaviors were
      identified as frequent pesticide use, washing pesticide equipment in water
      sources used by humans, inadequate disposal of empty pesticide containers, eating
      and drinking during pesticide application, and using inadequate protective
      clothing. Training and educational campaigns on pesticide use should be
      encouraged for this cohort, along with suggestions for alternative methods of
      pest control.

PMID- 14655904
TI  - Bacteria and disinfection byproducts in water from southern Mexico City.
AB  - Disinfection byproducts and microorganisms present in drinking water may have
      deleterious effects on human health. The authors examined bacterial indicators
      (enterobacteria and Helicobacter pylori [H. pylori]), physicochemical parameters,
      and trihalomethane (THM) levels to conduct a water quality evaluation in Mexico
      City, where little is known about disinfection byproducts and microbial counts.
      Analyses were performed by standard membrane filtration for the enumeration of
      total coliforms, fecal coliforms, fecal streptococci, and Vibrio species. Other
      testing consisted of polymerase chain reaction (PCR) for H. pylori,
      physicochemical parameters by selective electrodes, and THMs by head-space with
      the use of a gas chromatograph. Indicator bacteria and enterobacteria were
      detected in 23% of samples, with significant differences between total coliforms,
      fecal coliforms, and fecal streptococci before and after chlorination. H. pylori
      was detected in 69% of samples prior to chlorination and 57% postchlorination.
      THM levels were < 200 microg/l. Chlorine concentrations ranged from < 0.05 mg/l
      to 35 mg/l. Disinfection at the well does not ensure good water quality for the
      Mexico City population. The next step will be the monitoring of water quality in
      the distribution system that supplies dwellings, as well as water obtained
      directly from the tap.

PMID- 14655905
TI  - Gestation stage-specific oxidative deoxyribonucleic acid damage from sidestream
      smoke in pregnant rats and their fetuses.
AB  - Transplacental exposure to environmental tobacco smoke (ETS) is a possible cancer
      risk factor in offspring. The authors exposed pregnant Sprague-Dawley rats to a
      relevant dose of ETS (1 mg/m3) from gestation day 4 to days 16 or 21. They then
      assayed tissues for levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG), a marker of
      oxidative deoxyribonucleic acid damage. ETS exposure ending on gestation day 16
      resulted in statistically significant increases in 8-oxo-dG in maternal liver and
      kidney and in fetal kidney. On gestation day 21, there were significant 8-oxo-dG
      increases in fetal liver and brain. These gestational stage- and tissue-specific
      increases of 1.2- to 1.4-fold are similar to the putative relative increases in
      risk of human cancers related to ETS.

PMID- 14655906
TI  - Trace metal content and estimated daily human intake from chicken eggs in Ibadan,
      Nigeria.
AB  - A total of 151 chicken eggs and 4 local chicken feeds purchased directly from the
      poultry farms, at the local markets, and along the roadsides of Ibadan, Nigeria,
      were analyzed for lead, cadmium, copper, iron, nickel, zinc, and cobalt by carbon
      graphite atomic absorption spectrophotometry. The authors found strong, positive
      correlations between the levels of metals in the feeds and the corresponding
      levels of metals in the eggs. The overall average concentrations (mg/kg) of each
      metal in eggs were as follows: lead, 0.59; cadmium, 0.07; copper, 0.78; iron,
      23.20; nickel, 0.03; zinc, 13.75; and cobalt, 0.01. The average estimated daily
      intake of lead, cadmium, copper, and iron per person was 19.5 microg, 2.4 microg,
      25.6 microg, and 762.3 microg, respectively, whereas daily intakes of nickel,
      zinc, and cobalt were 0.9 microg, 452.1 microg, and 0.2 microg per person. The
      concentrations of some metals in eggs from this study did not differ appreciably
      from levels determined in eggs from other countries; concentrations of lead and
      cadmium in the current study, however, were comparatively greater than levels
      found in other countries. Therefore, the estimated daily intakes of lead and
      cadmium in this region slightly exceeded the normal reported daily intakes of
      lead and cadmium from eggs in some other countries.

PMID- 14655907
TI  - Opening up new avenues for insomnia treatment research.

PMID- 14655908
TI  - Where you least expect it: dopamine in the pons and modulation of sleep and REM
      sleep.

PMID- 14655909
TI  - Subjective surrogates of performance during night work.

PMID- 14655910
TI  - Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of
      a randomized, double-blind, placebo-controlled study in adults with chronic
      insomnia.
AB  - STUDY OBJECTIVES: To determine the long-term efficacy of eszopiclone in patients
      with chronic insomnia. DESIGN: Randomized, double-blind, multicenter, placebo
      controlled. SETTING: Out-patient, with monthly visits. PATIENTS: Aged 21 to 69
      years meeting DSM IV criteria for primary insomnia and reporting less than 6.5
      hours of sleep per night, and/or a sleep latency of more than 30 minutes each
      night for at least 1 month before screening. INTERVENTIONS: Eszopiclone 3 mg (n =
      593) or placebo (n = 195), nightly for 6 months MEASUREMENTS AND RESULTS:
      Efficacy was evaluated weekly using an interactive voice-response system.
      Endpoints included sleep latency; total sleep time; number of awakenings; wake
      time after sleep onset; quality of sleep; and next-day ratings of ability to
      function, daytime alertness, and sense of physical well-being. At the first week
      and each month for the study duration, eszopiclone produced significant and
      sustained improvements in sleep latency, wake time after sleep onset, number of
      awakenings, number of nights awakened per week, total sleep time, and quality of
      sleep compared with placebo (P < or = 0.003). Monthly ratings of next-day
      function, alertness, and sense of physical well-being were also significantly
      better with the use of eszopiclone than with placebo (P < or = 0.002). There was
      no evidence of tolerance, and the most common adverse events were unpleasant
      taste and headache. CONCLUSIONS: Throughout 6 months, eszopiclone improved all of
      the components of insomnia as defined by DSM-IV, including patient ratings of
      daytime function. This placebo-controlled study of eszopiclone provides
      compelling evidence that long-term pharmacologic treatment of insomnia is
      efficacious.

PMID- 14655911
TI  - Dopaminergic modulation of behavioral states in mesopontine tegmentum: a reverse
      microdialysis study in freely moving cats.
AB  - STUDY OBJECTIVES: We investigated the role of dopamine (DA) in behavioral state
      control and, in particular, paradoxical (or rapid eye movement) sleep (PS)
      generation in mesopontine structures. DESIGN: Reverse microdialysis and
      polygraphic recordings in freely moving cats were used to assess the effects on
      sleep-wake states of applied DA and monoaminergic agonists and antagonists.
      SETTINGS: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTION: NA. MEASUREMENTS AND
      RESULTS: Quantitative and qualitative analysis of behavioral states and
      electroencephalogram showed that DA had no significant effect when applied to any
      part of the mesopontine tegmentum, except the peri-locus coeruleus alpha, a
      region located just ventromedial to the locus coeruleus, pars alpha, and
      critically implicated in PS generation. In this structure, DA caused a selective
      and dose-dependent inhibition of PS and induced PS without atonia. These effects
      were not mimicked by SKF-81297, a selective D1-like agonist, or selective D2-like
      agonists such as quinelorane, quinpirole, and 7-OH-DPAT. Instead, D2-like
      agonists induced a significant decrease in wakefulness and increases in both slow
      wave sleep and PS. The effects of DA were mimicked, however, by application of
      clonidine, a selective alpha2 adrenoceptor agonist, and blocked by co-application
      of RX821002, a selective antagonist of alpha2 adrenoceptors. CONCLUSIONS: Our
      results indicate that DA inhibits PS in the peri-locus coeruleus alpha via
      excitation of alpha2 adrenoceptors, but application of D2-like agonists to the
      same region markedly decreases wakefulness and increases both slow-wave sleep and
      PS. This effect may be responsible for the excessive daytime sleepiness and sleep
      attacks induced by antiparkinsonian dopaminergic agents.

PMID- 14655912
TI  - Report of a case of immunosuppression with prednisone in an 8-year-old boy with
      an acute onset of hypocretin-deficiency narcolepsy.
AB  - OBJECTIVE: To explore whether acute destruction of hypocretin cells in a patient
      with narcolepsy could be detected and if the course of the disease could be
      reversed or altered by the use of prednisone for immunosuppression. DESIGN: Case
      report. SETTING: A sleep-clinic population in a tertiary-care hospital. PATIENT:
      An 8-year-old boy with a very acute recent (< 2 month) onset of sleepiness.
      METHODS: Sleep studies; fluid-attenuated inversion recovery and gadolinium
      magnetic resonance imaging studies with a focus on the hypothalamus; examinations
      of cerebrospinal fluid for cytology, protein, and hypocretin-1 levels; and HLA
      typing were performed. INTERVENTION: A 3-week regimen of 1 mg x kg(-1) x day(-1)
      of prednisone was administered in an attempt to modify the course of the disease.
      RESULTS AND CONCLUSION: Sleep evaluations were consistent with a diagnosis of
      narcolepsy. Hypocretin-1 was absent in the cerebrospinal fluid, and HLA-DQB1*0602
      was present. All other results were within normal limits, and prednisone did not
      have any noticeable effects. Clinical manifestation of narcolepsy might occur
      when the hypocretin cell damage is too advanced to be reversible.

PMID- 14655913
TI  - Cabergoline is an effective single-drug treatment for restless legs syndrome:
      clinical and actigraphic evaluation.
AB  - STUDY OBJECTIVES: To evaluate the efficacy and the safety of cabergoline, a
      dopamine-receptor agonist with a long half-life, in restless legs syndrome (RLS).
      DESIGN: A 2 month, single blind, open labeled clinical trial. Patients were
      evaluated with polysomnography at baseline (B), following 1 week of placebo (T0),
      and after 1 week (T1) and 2 months (T2) of cabergoline treatment. The clinical
      global impression was assessed using International RLS Study Group Rating Scale
      and nocturnal actigraphy. SETTING: Sleep Disorders Center. PATIENTS: Twelve
      patients with moderate to severe RLS (mean age 56.6 years) who were naive to
      treatment with dopaminergic agents. INTERVENTIONS: Upward titration of
      cabergoline (from 0.5 mg to 2 mg) in a single evening dose. MEASUREMENTS AND
      RESULTS: Ten patients completed the study (mean dose, 1.1 mg), and all showed an
      improvement of RLS symptoms. The results from the International RLS Study Group
      Rating Scale showed similarities between B (24.3+/-2.9) and T0 (23.1+/-5.9;
      P=0.6), with significant improvement at T1 (12.5+/-6.0; P=0.01 vs B and T0) and
      T2 (9.8+/-6.9; P=0.001 vs B and P=0.005 vs T0). The mean nocturnal activity value
      measured by actigraphy during week 1 decreased from T0 (19.8+/-9.3) to T1 (13.6+/
      6.4) and dropped significantly at T2 (8.5+/-5.3; P=0.05). Nine patients continued
      the treatment up to 12 months with consistent efficacy, few side effects, and no
      augmentation. CONCLUSIONS: Low doses of cabergoline showed effectiveness and
      safety in patients with moderate to severe RLS, with no appearance of
      augmentation phenomenon. Double blind, crossover, polysomnographic studies are
      necessary to confirm this preliminary data.

PMID- 14655914
TI  - Pramipexole in the management of restless legs syndrome: an extended study.
AB  - STUDY OBJECTIVES: To determine whether pramipexole used over an extended time for
      restless legs syndrome (RLS) remains effective; whether the dose of the drug
      needs to be increased; whether augmentation develops; and whether side effects,
      especially sleepiness, are prominent. DESIGN: Retrospective review of the records
      of consecutive patients treated with pramipexole for RLS. SETTING: Sleep
      disorders center in an academic hospital. PATIENTS: 60 consecutive patients
      treated with pramipexole for RLS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS:
      Pramipexole was completely effective in controlling RLS in 67%, partially
      effective in 27%, and ineffective in 7% of patients. Eleven patients (18%)
      discontinued pramipexole after less than 4 months; the remainder were followed
      for a mean of 27.2 months, during which only 4 others stopped the drug. The
      median daily dose increased from 0.38 mg after stabilization to 0.63 mg at the
      end of the study. Forty percent experienced mild side effects, most commonly
      insomnia, nausea or dyspepsia, and dizziness. Only 5% experienced sleepiness, and
      none experienced sleep attacks while driving. Augmentation developed in 33%, most
      in the first year and all by 30 months. Augmentation was not predictable by prior
      augmentation with other dopaminergic agents. Only 1 patient discontinued
      pramipexole because of augmentation. CONCLUSIONS: Pramipexole was effective for
      RLS with continued response with time. Modest escalations in dose occurred,
      partly due to additional doses prescribed for augmentation. Side effects were
      common, but generally mild and tolerated. Sleepiness while driving was not a
      problem. Augmentation occurred in 33% of patients but was treatable with
      increased doses earlier in the day.

PMID- 14655915
TI  - Sleep endocrine effects of the 11-beta-hydroxysteroiddehydrogenase inhibitor
      metyrapone.
AB  - STUDY OBJECTIVES: Besides regulating hormone secretion, steroids also modulate
      sleep architecture in specific ways. To simulate a state of altered
      glucocorticoid- and mineralocorticoid-receptor occupation, we administered
      metyrapone, an 11-beta-hydroxylase inhibitor, that blocks adrenal cortisol
      synthesis and inhibits the 11-beta-hydroxysteroiddehydrogenase type-1 enzyme in
      the central nervous system and investigated endocrine changes and the sleep
      electroencephalogram. DESIGN: Each volunteer spent 4 nights in the sleep
      laboratory, the first of which served to habituate the subject to the conditions
      in the laboratory. The volunteers underwent 3 trial conditions in random order
      and in a single-blind design receiving 2 doses of metyrapone (4.5 g or 6.0 g) or
      placebo on the day before the sleep electroencephalogram recordings. SETTING:
      Sleep laboratory. PARTICIPANTS: 8 healthy male volunteers. MEASUREMENTS AND
      RESULTS: The corticotropin secretion was significantly enhanced by metyrapone,
      while the cortisol secretion remained largely unchanged. Growth hormone,
      progesterone, and dehydroepiandrosterone concentrations were also significantly
      increased by both doses. Metyrapone induced a pronounced reduction in slow-wave
      sleep and had slight but nonlinear effects upon rapid eye movement sleep.
      Parameters of sleep quality were not different between groups. CONCLUSIONS:
      Metyrapone induces pronounced effects on hormonal secretion and the sleep
      electroencephalogram. These results are in part comparable to those from
      experiments with the administration of corticotropin-releasing hormone and with
      experiments that deplete mineralocorticoid receptors. The findings may be
      explained by altered steroid synthesis proximal to the enzyme block. Metyrapone
      exerts not only effects upon adrenocortical steroid synthesis, but also important
      extra-adrenal effects on central corticosteroid metabolism.

PMID- 14655916
TI  - Effects of a yearlong moderate-intensity exercise and a stretching intervention
      on sleep quality in postmenopausal women.
AB  - STUDY OBJECTIVES: To examine the effects of a moderate-intensity exercise or
      stretching intervention and changes in fitness, body mass index, or time spent
      outdoors on self-reported sleep quality and to examine the relationship between
      the amount and timing of exercise and sleep quality. DESIGN: A randomized
      intervention trial. SETTING: A cancer research center in Seattle, Washington.
      PARTICIPANTS: Postmenopausal, overweight or obese, sedentary women not taking
      hormone replacement therapy, aged 50 to 75 years, and recruited from the Seattle
      metropolitan area. INTERVENTIONS: A yearlong moderate-intensity exercise (n=87)
      and a low-intensity stretching (n=86) program. MEASUREMENTS AND RESULTS: Among
      morning exercisers, those who exercised at least 225 minutes per week had less
      trouble falling asleep (odds ratio [OR]: 0.3, P < or = .05) compared with those
      who exercised less than 180 minutes per week. However, among evening exercisers,
      those who exercised at least 225 minutes per week had more trouble falling asleep
      (OR: 3.3, P < or = .05) compared to those who exercised less than 180 minutes per
      week. Stretchers were less likely to use sleep medication (OR = 0.4, P < or =
      .05) and have trouble falling asleep (OR: 0.7, P < or = .10) during the
      intervention period compared with baseline. A greater than 10% versus a 1% or
      less increase in maximum O2 consumption over the year was associated with longer
      sleep duration (P < or = .05), less frequently falling asleep during quiet
      activities (P < or = .05), and less use of sleep medication (P < or = .05).
      Reductions in body mass index and increases in time spent outdoors had
      inconsistent effects on sleep quality. CONCLUSIONS: Both stretching and exercise
      interventions may improve sleep quality in sedentary, overweight, postmenopausal
      women. Increased fitness was associated with improvements in sleep. However, the
      effect of moderate-intensity exercise may depend on the amount of exercise and
      time of day it is performed.

PMID- 14655917
TI  - Bed sharing, sleep habits, and sleep problems among Chinese school-aged children.
AB  - STUDY OBJECTIVES: This study examined the association between bed sharing, sleep
      habits, and sleep problems among Chinese school-aged children. DESIGN AND
      SETTING: A questionnaire survey of school-aged children was undertaken in Jinan
      city, People's Republic of China, in 2001. PARTICIPANTS: A total of 517
      elementary-school children (mean age, 10.5 years; 47.4% boys) participated in the
      survey. MEASUREMENTS: The parents completed the Chinese version of the Children's
      Sleep Habits Questionnaire and a number of questions that asked about bed sharing
      and characteristics of the family and child. RESULTS: The prevalence of regular
      bed sharing in Chinese school-aged children was as high as 18.2%. The rate of bed
      sharing did not differ between boys and girls but significantly decreased with
      age from 55.8% in 7-year-olds to 7.2% in 11- to 13-year-olds. Multivariate
      logistic regression analysis showed that younger age, poor physical health of the
      child, and crowded housing were associated with an increased likelihood for the
      child's bed sharing with parents. Bedtime and total sleep duration did not
      significantly differ between children who shared beds and those who slept alone.
      Children who shared beds with their parents were reported to have more sleep
      anxiety and daytime sleepiness than children who slept alone. Bed sharing was not
      associated with parasomnias and breathing problems during sleep. CONCLUSIONS:
      Regular bed sharing in Chinese school-aged children was very common and
      significantly decreased with age. Crowded housing and poor physical health of the
      child increased the likelihood for children and parents to share beds. Bed
      sharing may exert influences on sleep quality rather than sleep quantity.

PMID- 14655918
TI  - Cardiac changes during sleep in sleep-deprived infants.
AB  - OBJECTIVE: To evaluate the influence of a brief period of sleep deprivation on
      cardiac autonomic controls during sleep in healthy infants. DESIGN: Twelve
      healthy infants with a median age of 8 weeks (range, 7 to 18 weeks) were recorded
      polygraphically during a morning and an afternoon nap in a sleep laboratory. They
      were sleep deprived for approximately 2 hours, either in the morning or in the
      afternoon, before being allowed to fall asleep. Six infants were sleep deprived
      before the morning nap, and 6 before the afternoon nap. During both naps, their
      sleep, breathing, and heart-rate characteristics were continuously recorded.
      Spectral analysis of heart rate was evaluated as a function of sleep stages. Two
      major peaks were recognizable: a low-frequency component related to sympathetic
      and parasympathetic activities and a high-frequency component reflecting
      parasympathetic tonus. The ratio of low-frequency to high-frequency powers was
      calculated as an index of sympathovagal interaction. RESULTS: When sleep
      deprived, the infants had an increase in basal heart rate during non-rapid eye
      movement sleep (P=.021). With sleep deprivation, the ratio of low-frequency to
      high-frequency powers increased in non-rapid eye movement sleep (P=.005). These
      findings were consistent with an increase in sympathetic tone. CONCLUSION:
      Infants exposed to short-term sleep deprivation manifest changes in cardiac
      autonomic controls during sleep. These findings could be relevant to mechanisms
      associated with the sudden infant death syndrome.

PMID- 14655919
TI  - The influence of lung volume on pharyngeal mechanics, collapsibility, and
      genioglossus muscle activation during sleep.
AB  - STUDY OBJECTIVES: Previous studies in both awake and sleeping humans have
      demonstrated that lung-volume changes substantially affect upper-airway size and
      pharyngeal resistance and, thus, may influence pharyngeal patency. We sought to
      systematically investigate the isolated effects of lung-volume changes on
      pharyngeal collapsibility and mechanics and genioglossus muscle activation during
      stable non-rapid eye movement sleep. We hypothesized that lower lung volumes
      would lead to increased pharyngeal collapsibility, airflow resistance, and, in
      compensation, augmented genioglossus muscle activation. DESIGN: Nineteen normal
      individuals (age, 30.4 +/- 0.5 years; body mass index: 24.5 +/- 0.4 kg/m2) were
      studied during stable non-rapid eye movement sleep in a rigid head-out shell
      equipped with a variable positive/negative pressure attachment for manipulations
      of extrathoracic pressure and, thus, lung volume. SETTING: Sleep physiology
      laboratory. PARTICIPANTS: Normal healthy volunteers. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: We measured change in end-expiratory lung volume (EELV)
      (magnetometers), genioglossus electromyogram (GGEMG) (intramuscular electrodes),
      pharyngeal pressure, and collapsibility of the pharynx in response to a brief
      pulse of negative pressure (-8 to -15 cm H2O) under the following conditions: (1)
      baseline, (2) increased EELV (+1 liter), and (3) decreased EELV (-0.6 liter).
      Reduced lung volumes led to increased inspiratory airflow resistance (7.54 +/-
      2.80 cm H2O x L(-1) x s(-1) vs 4.53 +/- 1.05 cm H2O x L(-1) x s(-1), mean +/-
      SEM, P = 0.02) and increased genioglossus muscle activation (GGEMG peak 14.6% +/-
      1.5% of maximum vs 8.6% +/- 1.5% of maximum, maximum P = 0.001) compared to
      baseline. The pharynx was also more collapsible at low lung volumes (4.3 +/- 0.5
      cm H2O vs 5.4 +/- 0.6 cm H2O, P = 0.04). CONCLUSIONS: We conclude that upper
      airway muscles respond to changes in lung volumes but not adequately to prevent
      increased collapsibility. These results suggest that lung volume has an important
      influence on pharyngeal patency during non-rapid eye movement sleep in normal
      individuals.

PMID- 14655920
TI  - Prediction of inspiratory flow shapes during sleep with a mathematic model of
      upper airway forces.
AB  - STUDY OBJECTIVES: To predict the airflow dynamics during sleep using a mathematic
      model that incorporates a number of static and dynamic upper airway forces, and
      to compare the numerical results to clinical flow data recorded from patients
      with sleep-disordered breathing on and off various treatment options. DESIGN:
      Upper airway performance was modeled in virtual subjects characterized by
      parameter settings that describe common combinations of risk factors predisposing
      to upper airway collapse during sleep. The treatments effect were induced by
      relevant changes of the initial parameter values. SETTING: Computer simulations
      at our website (http://www.utu.fi/ml/sovmat/bio/). PARTICIPANTS: Risk factors
      considered in the simulation settings were sex, obesity, pharyngeal
      collapsibility, and decreased phasic activity of pharyngeal muscles.
      INTERVENTIONS: The effects of weight loss, pharyngeal surgery, nasal continuous
      positive airway pressure, and respiratory stimulation on the inspiratory flow
      characteristics were tested with the model. MEASUREMENTS AND RESULTS: Numerical
      predictions were investigated by means of 3 measurable inspiratory airflow
      characteristics: initial slope, total volume, and flow shape. The model was able
      to reproduce the inspiratory flow shape characteristics that have previously been
      described in the literature. Simulation results also supported the observations
      that a multitude of factors underlie the pharyngeal collapse and, therefore,
      certain medical therapies that are effective in some conditions may prove
      ineffective in others. CONCLUSIONS: A mathematic model integrating the current
      knowledge of upper airway physiology is able to predict individual treatment
      responses. The model provides a framework for designing novel and potentially
      feasible treatment alternatives for sleep-disordered breathing.

PMID- 14655921
TI  - A randomized, double-blind clinical trial comparing continuous positive airway
      pressure with a novel bilevel pressure system for treatment of obstructive sleep
      apnea syndrome.
AB  - STUDY OBJECTIVES: To obtain efficacy, objective compliance, and self-assessment
      data from obstructive sleep apnea syndrome (OSAS) patients treated with
      continuous positive airway pressure (CPAP) or a novel bilevel (NBL) therapy.
      DESIGN: Randomized, controlled, double-blind trial. SETTING: Home treatment after
      diagnosis and titration by split-night polysomnography (PSG) in a sleep
      laboratory. PATIENTS: Twenty-seven adults (22 men) newly referred for suspected
      OSAS but without concomitant medical or sleep disorders. INTERVENTIONS: If the
      subject's apnea-hypopnea index was greater than 10 and less than 100, the CPAP
      was titrated during PSG and then followed by NBL titration. Treatment was
      randomly and blindly set to either CPAP or NBL mode for 1 month. MEASUREMENTS &
      RESULTS: There were no significant baseline group differences in age, body mass
      index, apnea-hypopnea index (mean +/- SD, CPAP group vs NBL group of 46.1 +/-
      23.1/hour vs 41.8 +/- 25.8), CPAP requirement, or scores on the Epworth
      Sleepiness Scale and Functional Outcomes of Sleep Questionnaire. Treatment with
      CPAP and NBL equivalently reduced the apnea-hypopnea index during the laboratory
      titration (7.6 +/- 11.9/hour vs. 3.7 +/- 4.4, respectively). At 1 month, there
      were no significant group compliance differences as determined by percentage of
      nights with at least 4 hours of use (CPAP, 80.5 +/- 24 vs NBL, 77.6 +/- 24.8) and
      hours of use per night (CPAP, 5.6 +/- 1.4 hours/night vs NBL, 5.6 +/- 1.7).
      Similar improvements were seen in scores on the Epworth Sleepiness Scale and
      Functional Outcomes of Sleep Questionnaire. CONCLUSIONS: The NBL appeared to be
      as effective as CPAP for the treatment of OSAS but offered no advantages in
      patients receiving first-time therapy for OSAS.

PMID- 14655922
TI  - The ability to self-monitor performance during a week of simulated night shifts.
AB  - STUDY OBJECTIVES: Research has indicated that individuals are able to accurately
      monitor the performance decrements they experience during unitary periods of
      acute sleep deprivation. The aim of the current study was to investigate the
      ability to self-monitor performance during a week of simulated night shifts.
      DESIGN: Subjects completed 7 consecutive 8-hour night shifts (11 pm-7 am).
      SETTING: University sleep laboratory. SUBJECTS: Fifteen young (7 men, 8 women, 19
      25 years) healthy volunteers. INTERVENTIONS: During the night shifts, performance
      was measured hourly on 4 performance parameters: psychomotor vigilance test
      (PVT), tracking, and grammatical reasoning (GRG) accuracy and response latency.
      Before and after each test, subjects completed visual analogue scales, which
      required them to rate their alertness and their performance speed and/or
      accuracy. RESULTS: Analysis indicated that GRG response latency and tracking were
      significantly impaired (P<0.05) during the first 2 shifts only. The PVT
      performance displayed consistent impairment, with significant (P<0.05) declines
      during all but the final shift. The pattern of deterioration in subjective
      ratings of alertness was similar to that of the PVT data. Correlations between
      subjective alertness and self-ratings of performance were significant (P<0.01)
      for all parameters (r=0.39-0.69). Significant (P<0.05) correlations were found
      across the week between pretest performance ratings and actual performance for
      all parameters except GRG accuracy (r=0.29-0.58) and between posttest ratings and
      actual performance for all parameters (r=0.52-0.75). Correlations between pretest
      ratings and actual performance were also conducted separately for each shift.
      Highest correlations were found during the first shift, with r-values that were
      low for GRG accuracy (r=0.32) and GRG response latency (r=0.20), moderate for
      tracking (r=0.41), and high for PVT (r=0.82). In general, lower correlations were
      found later in the week. CONCLUSIONS: Overall, results indicate that individuals
      have only a moderate ability to predict performance impairment during a week of
      night shifts. It is likely that performance ratings are based, at least to a
      certain extent, on subjective alertness levels. Furthermore, it seems that rating
      accuracy is improved on tasks providing performance feedback, such as the PVT.
      Finally, it appears that after testing, individuals have a more accurate
      perception of their performance.

PMID- 14655923
TI  - The clinical predictors of sleepiness correlated with the multiple sleep latency
      test in an Asian Singapore population.
AB  - STUDY OBJECTIVES: To explore the clinical predictors of sleepiness as objectively
      determined by the Multiple Sleep Latency Test with the Epworth Sleepiness Scale,
      age, body mass index, and overnight polysomnographic parameters at a tertiary
      referral center Sleep Disorders Unit. DESIGN: Retrospective, consecutive case
      series review. SETTING: A multidisciplinary sleep disorders unit in Singapore
      General Hospital, a tertiary-care university-affiliated hospital. PATIENTS: 72
      consecutive patients evaluated for sleep disorders with overnight polysomnograms
      and Multiple Sleep Latency Tests between March 2002 and September 2002.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Mean sleep latency on the Multiple
      Sleep Latency Test was 9.0 +/- 4.4 minutes, and mean Epworth Sleepiness Scale
      score was 10.8 +/- 5.8. On univariate analysis, mean sleep latency on the
      Multiple Sleep Latency Test showed a significant negative correlation with the
      Epworth Sleepiness Scale score, apnea-hypopnea index, body mass index, arousal
      index, and time spent below 90% oxygen saturation during overnight
      polysomnography. After performing multiple linear regression, only Epworth
      Sleepiness Scale score and apnea-hypopnea index remained significantly correlated
      (P = .039 and P = .008, respectively). An Epworth Sleepiness Scale score of 8 or
      above predicted a mean sleep latency on the Multiple Sleep Latency Test of less
      than 10 minutes with a sensitivity of 73.9% and specificity of 50.0%.
      CONCLUSIONS: The Epworth Sleepiness Scale and apnea-hypopnea index are useful
      predictors of sleepiness in our Asian Singapore population.

PMID- 14655924
TI  - Nocturnal frontal lobe epilepsy: intracerebral recordings of paroxysmal motor
      attacks with increasing complexity.
AB  - PURPOSES: To show the results of the investigation conducted with intracerebral
      electrodes in a patient with drug-resistant nocturnal frontal lobe epilepsy,
      characterized by sleep-related paroxysmal motor attacks of increasing complexity
      ranging from simple and brief stereotyped motor events to paroxysmal arousals and
      major attacks. METHODS: The patient was studied with long-term video-stereo
      electroencephalographic monitoring by means of stereotactically implanted
      intracerebral electrodes. RESULTS: Video-stereo-electroencephalography
      demonstrated that minor events and paroxysmal arousals, as well as major attacks,
      were correlated with a discharge in the right supplementary motor area and
      central cingulate gyms. The increasing complexity of these sleep-related ictal
      motor behaviors reflected a different pattern of discharge, with a progressive
      spread to other frontal and extrafrontal areas in the fully developed attacks.
      Surgical resection of the right supplementary motor area and central cingulate
      gyrus was performed. In the 5 years since the operation, the patient has remained
      completely seizure free. CONCLUSION: This study clearly demonstrates the ictal
      origin of minor events in nocturnal frontal lobe epilepsy. The increasing
      complexity of the motor behaviors from minor to major attacks reflects different
      duration, amplitude, and spread of the epileptic discharge.

PMID- 14655925
TI  - Association between nocturnal bruxism and gastroesophageal reflux.
AB  - STUDY OBJECTIVE: To examine the relationship between nocturnal bruxism and
      gastroesophageal reflux. DESIGN: Controlled descriptive study and double-blind,
      placebo-controlled, clinical study. SETTING: Portable pH monitoring,
      electromyography, and audio-video recordings were conducted during the night in
      the subjects' home. PARTICIPANTS: Ten patients with bruxism and 10 normal
      subjects were matched for height, weight, age, and sex. They did not have
      symptoms of gastroesophageal reflux disease. INTERVENTION: Medication with a
      proton pump inhibitor (ie, a gastric-acid-inhibiting drug). MEASUREMENTS AND
      RESULTS: The bruxism group showed a significantly higher frequency of nocturnal
      rhythmic masticatory muscle activity (RMMA) episodes (mean +/- SD: 6.7 +/- 2.2
      times per hour) and a higher frequency and percentage of time of gastroesophageal
      reflux episodes with a pH less than 4.0 and 5.0 (0.5 +/- 0.9 and 3.6 +/- 1.6
      times per hour and 1.3% +/- 2.5% and 7.4% +/- 12.6%, respectively) than the
      control group (RMMA episodes: 2.4 +/- 0.9 times per hour; gastroesophageal reflux
      episodes: 0.0 +/- 0.0 and 0.1 +/- 0.3 times per hour and 0.0% +/- 0.0% and 0.0%
      +/- 0.0%, respectively). In the bruxism group, 100% of the gastroesophageal
      reflux episodes with a pH less than 3.0 and 4.0 included both an RMMA episode and
      an electromyographic burst, the duration of which was approximately 0.5 to 1.0
      seconds, probably representing swallowing of saliva. The majority of
      gastroesophageal reflux episodes with a pH of 4.0 to 5.0 also included both an
      RMMA episode and an electromyographic burst in the control and bruxism groups
      (100% +/- 0.0% vs 70.7% +/- 16.5%), again probably due to swallowing of saliva.
      The remaining minority of gastroesophageal reflux episodes with a pH of 4.0 to
      5.0 contained only an electromyographic burst (swallowing of saliva). The
      frequency of RMMA episodes after the release of the medication from the proton
      pump inhibitor, which increased the gastric and esophageal pH, was significantly
      lower than that after administration of the placebo in the control and bruxism
      groups (1.0 +/- 0.6 vs 1.9 +/- 3.2 times per hour, and 3.7 +/- 1.9 vs. 6.0 +/-
      2.2 times per hour, respectively). CONCLUSIONS: Nocturnal bruxism may be
      secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and
      often together with swallowing. The physiologic link between bruxism and the
      increase in salivation needs to be investigated.

PMID- 14655927
TI  - Actigraphy in the assessment of insomnia.
AB  - OBJECTIVE: The present study explores the clinical utility and sensitivity of
      actigraphy as an outcome measure in the treatment of chronic insomnia. DESIGN:
      Following a screening-adaptation night, polysomnography, actigraphy, and sleep
      diary data were collected in the sleep laboratory for 2 baseline nights and 2
      posttreatment nights. SETTING: A university-affiliated sleep disorders center.
      PARTICIPANTS: Seventeen participants with chronic primary insomnia. Mean age was
      41.6 years. INTERVENTIONS: Participants took part in a treatment protocol
      investigating different sequential treatments for insomnia (these results are
      reported elsewhere). MEASUREMENTS AND RESULTS: Compared to polysomnography, both
      actigraphy and sleep-diary instruments underestimated total sleep time and sleep
      efficiency and overestimated total wake time. Also, actigraphy underestimated
      sleep-onset latency while the sleep diary overestimated it as compared to
      polysomnography. Actigraphy data were more accurate than sleep-diary data when
      compared to polysomnography. Finally, actigraphy was sensitive in detecting the
      effects of treatment on several sleep parameters. CONCLUSIONS: These results
      suggest that actigraphy is a useful device for measuring treatment response and
      that it should be used as a complement to sleep-diary evaluation.

PMID- 14655926
TI  - A multicenter, placebo-controlled trial of melatonin for sleep disturbance in
      Alzheimer's disease.
AB  - OBJECTIVES: To determine the safety and efficacy of 2 dose formulations of
      melatonin for the treatment of insomnia in patients with Alzheimer's disease.
      DESIGN: A multicenter, randomized, placebo-controlled clinical trial of 2 dose
      formulations of oral melatonin coordinated by the National Institute of Aging
      funded Alzheimer's Disease Cooperative Study. Subjects with Alzheimer's disease
      and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment
      groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin. SETTING:
      Private homes and long-term care facilities. PARTICIPANTS: 157 individuals were
      recruited by 36 Alzheimer's disease research centers. Subjects with a diagnosis
      of Alzheimer's disease were eligible if they averaged less than 7 hours of sleep
      per night (as documented by wrist actigraphy) and had 2 or more episodes per week
      of nighttime awakenings reported by the caregiver. MEASUREMENTS: Nocturnal total
      sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep
      ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was
      defined by an automated algorithmic analysis of wrist actigraph data. RESULTS: No
      statistically significant differences in objective sleep measures were seen
      between baseline and treatment periods for the any of the 3 groups.
      Nonsignificant trends for increased nocturnal total sleep time and decreased wake
      after sleep onset were observed in the melatonin groups relative to placebo.
      Trends for a greater percentage of subjects having more than a 30-minute increase
      in nocturnal total sleep time in the 10-mg melatonin group and for a decline in
      the day-night sleep ratio in the 2.5-mg sustained-release melatonin group,
      compared to placebo, were also seen. On subjective measures, caregiver ratings of
      sleep quality showed improvement in the 2.5-mg sustained-release melatonin group
      relative to placebo. There were no significant differences in the number or
      seriousness of adverse events between the placebo and melatonin groups.
      CONCLUSIONS: Based on actigraphy as an objective measure of sleep time, melatonin
      is not an effective soporific agent in people with Alzheimer's disease.

PMID- 14655928
TI  - Practice parameters for the use of portable monitoring devices in the
      investigation of suspected obstructive sleep apnea in adults.
AB  - BACKGROUND: A variety of devices are used to evaluate patients with a potential
      diagnosis of obstructive sleep apnea (OSA). A committee comprised of members of
      the American Academy of Sleep Medicine, American Thoracic Society, and American
      College of Chest Physicians systematically evaluated data on the use of these
      devices and developed practice parameters. DEVICES REVIEWED: Three categories of
      portable monitoring (PM) devices were reviewed with regard to assessing the
      probability of identifying an apnea-hypopnea index (AHI) of greater or less than
      15 in attended and unattended settings. Type 2 (minimum of seven channels,
      including EEG, EOG, chin EMG, ECG or heart rate, airflow, respiratory effort,
      oxygen saturation), Type 3 (minimum of four channels, including ventilation or
      airflow (at least two channels of respiratory movement, or respiratory movement
      and airflow), heart rate or ECG and oxygen saturation) and Type 4 (most monitors
      of this type measure a single parameter or two parameters) devices were
      evaluated, and in-laboratory, attended polysomnography was used as a reference.
      SPECIFIC RECOMMENDATIONS: (1) Insufficient evidence is available to recommend the
      use of Type 2 PM devices in attended or unattended settings. (2) Type 3 PM
      devices appear to be capable of being used in an attended setting to increase or
      to decrease the probability that a patient has an apnea-hypopnea index greater
      than 15. (3) The use of Type 3 PM devices in an unattended setting is not
      recommended to rule in, rule out, or both rule in and rule out a diagnosis of
      OSA. (4) There is some evidence that the use of Type 3 PM devices in an attended
      in-laboratory setting may be acceptable to both rule in and rule out a diagnosis
      of OSA if certain limitations are in place. These limitations include manually
      scoring the records, using the devices only in patients without significant
      comorbid conditions, having an awareness that symptomatic patients with a
      negative study should have a Type 1 study, and not using these devices for
      titrating positive airway pressure or conducting split-night studies. (5) The use
      of Type 4 PM devices in attended or unattended settings is not recommended.
      GENERAL RECOMMENDATIONS: Type 3 and 4 PM devices cannot score sleep and,
      therefore, do not meet some current Medicare guidelines. The use of PM devices is
      not recommended for general-population screening or in the absence of a pretest
      probability of the patient having a diagnosis of OSA, for complaints other than
      those associated with OSA, without review of raw data during interpretation, by
      physicians without familiarity with their use and limitations, and without
      trained personnel to perform technical scoring. Future research should address
      the use of PM devices in patients with comorbid conditions; non-White patients
      and women; larger, better-controlled studies; studies focused on the use of Type
      2 and 3 devices; studies focusing on decision making and outcomes rather than
      simple classification using arbitrary cutoffs; and studies that seek to elucidate
      cost-effectiveness data on the use of PM devices.

PMID- 14655929
TI  - Airline acceptability of in-flight CPAP machines--flight, fright, or fight?

PMID- 14655930
TI  - Functional MRI is fundamentally limited by an inadequate understanding of the
      origin of fMRI signals in tissue. For the proposition.

PMID- 14655931
TI  - Functional MRI is fundamentally limited by an inadequate understanding of the
      origin of fMRI signals in tissue. Against the proposition.

PMID- 14655932
TI  - Effect of vessel orientation on videodensitometry quantitative coronary
      arteriography.
AB  - Cross-sectional area measurement using videodensitometry coronary arteriography
      is a function of the out-of-plane angle of the vessel segment with respect to the
      face of the image intensifier. Therefore, absolute cross-sectional area
      measurement using videodensitometry requires correction for the out-of-plane
      angle. In this study, a simple technique to measure the out-of-plane angle of a
      vessel segment using images from two different projections is presented. The
      technique was tested using vessel phantoms imaged at different out-of-plane
      angles. A vessel segment with an out-of-plane angle of less than 20 degrees
      introduces less than 5% error in the cross-sectional area measurements. However,
      an out-of-plane angle of 60 degrees can introduce more than 90% error. The
      results of the measurements show that correction for the out-of-plane angle
      reduces the error in cross-sectional area measurement to less that 5%. The
      correction for the out-of-plane angle makes it possible to measure the absolute
      cross-sectional area using videodensitometery, which can be used to assess a
      diseased vessel segment with any complex geometry.

PMID- 14655933
TI  - Fundamental image quality limits for microcomputed tomography in small animals.
AB  - Small-animal imaging has become increasingly more important as transgenic and
      knockout mice are produced to model human diseases. One imaging technique that
      has emerged is microcomputed tomography (micro-CT). For live-animal imaging, the
      precision in the images will be determined by the x-ray dose given to the animal.
      As a result, we propose a simple method to predict the noise performance of an x
      ray micro-CT system as a function of dose and image resolution. An ideal, quantum
      noise limited micro-CT scanner, assumed to have perfect resolution and ideal
      efficiency, was modeled. Using a simplified model, the coefficient of variation
      (COV) of the linear attenuation coefficient was calculated for a range of
      entrance doses and isotropic voxel sizes. COV calculations were performed for the
      ideal case and with simulated imperfections in efficiency and resolution. Our
      model was validated in phantom studies and mouse images were acquired with a
      specimen scanner to illustrate the results. A simplified model of noise
      propagation in the case of isotropic resolution indicates that the COV in the
      linear attenuation coefficient is proportional to (dose)(-1/2) and to the
      (isotropic voxel size)(-2) in the reconstructed volume. Therefore an improvement
      in the precision can be achieved only by increasing the isotropic voxel size
      (thereby decreasing the resolution of the image) or by increasing the x-ray dose.
      For the ideal scanner, a COV of 1% in the linear attenuation coefficient for an
      image of a mouse exposed to 0.25 Gy is obtained with a minimum isotropic voxel
      size of 135 microm. However, the same COV is achieved at a dose of 5.0 Gy with a
      65 microm isotropic voxel size. Conversely, for a 68 mm diameter rat, a COV of 1%
      obtained from an image at 5.0 Gy would require an isotropic voxel size of 100
      microm. These results indicate that short-term, potentially lethal, effects of
      ionizing radiation will limit high-resolution live animal imaging. As
      improvements in detector technology allow the resolution to improve, by
      decreasing the detector element size to tens of microns or less, high quality
      images will be limited by the x-ray dose administered. For the highest quality
      images, these doses will approach the lethal dose or LD50 for the animals.
      Approaching the lethal dose will affect the way experiments are planned, and may
      reduce opportunities for experiments involving imaging the same animal over time.
      Dose considerations will become much more important for live small-animal imaging
      as the limits of resolution are tested.

PMID- 14655934
TI  - Independent verification of ultrasound based image-guided radiation treatment,
      using electronic portal imaging and implanted gold markers.
AB  - The aim of this paper is to study the correction of prostate motion and position
      during external beam therapy. The correction was performed using a commercially
      available ultrasound-based repositioning tool. Electronic portal imaging with the
      use of fiducial markers was used to assess efficacy and accuracy. Patients
      undergoing radiation treatment for adenocarcinoma of the prostate were enrolled
      in a positioning study. Fifteen patients had five to six gold fiducial markers
      implanted in their prostate. These patients were positioned daily in a standard
      manner and then were repositioned every other day using an ultrasound-based
      correction system. Every fraction of a patients' treatment was imaged. This
      yielded 156 image pairs with and 119 pairs without repositioning available for
      analysis. This group of patients with markers had the following residual
      positions measured after the use of ultrasound repositioning. A mean error of 
      0.4 mm (LL), -2.6 mm (CC), and +2.5 mm (AP) with a standard deviation of 4.3,
      5.4, and 5.7 mm. In two directions the improvements of treatment using the
      ultrasound correction were smaller than the precision of this experiment. They
      were no larger than 0.81 mm (LAT), and 0.95 mm (CC). In the AP direction a
      significant improvement was found of 1.6 mm. A highly significant correlation (p
      < 0.001) was found between the residual errors in the cranio-caudal direction and
      the shifts performed on the basis of the ultrasound measurements (Spearman
      ranking R = 0.53). We presented a method to objectively estimate improvements by
      a correction scheme. This method applied to ultrasound-based adjustment showed
      significant improvement in one direction and no measurable improvement in two
      other directions.

PMID- 14655935
TI  - Quantification of the effect of system and object parameters on edge enhancement
      in phase-contrast radiography.
AB  - The purpose of this study was to evaluate the effects of system parameters (focal
      spot size, tube voltage, geometry, detector resolution, and image noise) and
      object characteristics (edge gradient/ shape, composition, thickness, and
      overlying attenuating material) upon the edge enhancement effect in phase
      contrast radiography. Each variable of interest was adjusted and images of a 3 mm
      lucite phantom were obtained with the other variables remaining constant. A
      microfocus x-ray source coupled to a CCD camera with an intensifying screen was
      used to acquire the digital images. Two parameters of image analysis were used to
      quantify the effects. The edge enhancement index (EEI) was used to measure the
      absolute degree of edge enhancement, while the edge enhancement to noise ratio
      (EE/N) was used to measure the conspicuity of the edge enhancement relative to
      image noise. Little effect on EEI was seen from tube voltage, object thickness,
      overlying attenuating material, while focal spot size and system geometry
      demonstrated measurable effects upon the degree of edge enhancement. It was also
      shown that while the edge enhancement effect over straight edges is highly
      dependent upon how the edge aligns with the x-ray beam, rounded edges, which
      better model biological objects, do not suffer from this dependence and the EEI
      reaches its maximal level at any alignment. Decreasing detector resolution
      diminished the EEI slightly, but even with pixel sizes of 0.360 x 0.360 mm edge
      enhancement effects were readily visible. The effect of image noise on EE/N was
      evaluated using different exposure times showing an expected improvement with
      longer exposure time with EE/N approaching a plateau at 5 min. Many of the
      parameters that will go into the design of a future PC-R imaging system have been
      quantified in terms of their effect on the degree of edge enhancement in the
      acquired image. These results, taken together, indicate that either a specimen or
      even clinical breast imaging system could be created with currently available
      technology. The major limitation to a clinical system would be the low x-ray flux
      from the microfocal x-ray source.

PMID- 14655936
TI  - Automatic post-implant needle reconstruction algorithm to characterize and
      improve implant robustness analyses.
AB  - Post-implant analysis in permanent implant brachytherapy is an important process
      that provides a feedback on treatment quality. Random seed movements, edema, and
      needle related factors contribute to deteriorate dose coverage. For a complete
      study of these movements, it is important to reconstruct the post-implant seeds
      clusters but, up to now, this task was only possible via a long and difficult
      manual process. To facilitate post-implant analysis a simulated annealing
      algorithm was developed to perform automatic reconstructions. This process is
      fast (30-60 s on a 1.3 GHz pentium) and has a high level of success, even with up
      to 5% of seed loss. Tests on 21 clinical cases show that the algorithm yields
      exactly the same results as manual reconstructions. A realistic simulation tool
      was used to generate 58 synthetic post-implant data, in which cases the exact
      configuration was known. Even if some errors were found, pertinent information
      was extracted. For medium seed density [corresponding to seeds of 0.6 mCi (0.762
      U)], 97% of seeds are matched with their correct needle and 89% are matched with
      their correct planned position. This method provides pertinent information that
      can be used to understand inhomogenous dose coverage in specific prostate
      quadrants; to make realistic post-implant simulations or to identify seeds
      belonging to a needle loaded with different seed types or activity.

PMID- 14655937
TI  - Basic dosimetry of radiosurgery narrow beams using Monte Carlo simulations: a
      detailed study of depth of maximum dose.
AB  - In radiosurgery narrow photon beams, the depth of maximum dose d(max), in the
      beam central axis increases as the size of the additional collimator increases.
      This behavior is the opposite of what is observed in radiotherapy conventional
      beams. To understand this effect, experimental depth dose curves of the
      additional collimators were obtained for a Siemens KD2 linear accelerator in 6 MV
      photon mode and the shift of d(max) varied from 11.0 +/- 0.6 mm for the 5 mm
      collimator to 14.5 +/- 0.6 mm for the 23 mm collimator. Monte Carlo simulations
      showed that the photons that had no interactions in the additional collimators,
      contributing more than 90% to the total dose in water, were responsible for the
      shift in d(max). Monte Carlo simulations also showed that electrons originated
      from these photons and contributing to the dose deposit in water in the beam
      central axis could be divided in two groups: those that deposit energy far away
      from their point of origin (the point of the first photon collision in water) and
      those that deposit energy locally (originated at more than one photon collision
      in water). Applying a simplified model based on the fact that the photons
      originating Compton electrons (at the first and subsequent collisions) have
      similar characteristics in air for all the additional collimators, it was shown
      that these electrons were also responsible for the shift of d(max) in the beam
      central axis. Finally, it was shown that the changes in the initial gradients of
      the depth dose curves of the additional collimators were mainly due to electrons
      originated from the first photon collision in water.

PMID- 14655938
TI  - Matched view weighting in tilted-plane-based reconstruction algorithms to
      suppress helical artifacts and optimize noise characteristics.
AB  - In multi-slice helical CT, the single-tilted-plane-based reconstruction algorithm
      has been proposed to combat helical and cone beam artifacts by tilting a
      reconstruction plane to fit a helical source trajectory optimally. Furthermore,
      to improve the noise characteristics or dose efficiency of the single-tilted
      plane-based reconstruction algorithm, the multi-tilted-plane-based reconstruction
      algorithm has been proposed, in which the reconstruction plane deviates from the
      pose globally optimized due to an extra rotation along the 3rd axis. As a result,
      the capability of suppressing helical and cone beam artifacts in the multi-tilted
      plane-based reconstruction algorithm is compromised. A matched view weighting
      approach is proposed here to optimize the capability of suppressing helical and
      cone beam artifacts and noise characteristics. A helical body phantom is employed
      to quantitatively evaluate the imaging performance of the matched view weighting
      approach, showing that the matched view weighting improves both the helical
      artifact suppression and noise characteristics or dose efficiency significantly
      in comparison to the case in which nonmatched view weighting is applied. The
      matched view weighting approach is of practical importance in the development of
      multi-slice helical CT, because it maintains the computational structure of fan
      beam filtered back-projection and demands no extra computational resources.

PMID- 14655939
TI  - Reproducibility of the assessment of tumor extent in the breast using multiple
      image modalities.
AB  - The accuracy of breast-conserving therapy (BCT) is limited by uncertainties in
      the assessment of tumor extent. These uncertainties may result in too wide
      treatment volumes leading to undesirable cosmetic results, or too narrow
      treatment volumes leading to higher probabilities of local recurrence. The aim of
      this study is to quantify the reproducibility of the assessment of tumor extent
      in the breast at preoperative diagnostic imaging with multiple imaging modalities
      and at pathology, applied to (1) determining minimum surgical safety margins to
      reduce the probability of underestimating the tumor extent due to uncertainty in
      the radiological assessment, and (2) defining the minimum difference between two
      measurements of tumor size that indicates a significant reduction of tumor extent
      in response to neoadjuvant chemotherapy or hormonal therapy. Measurements of the
      largest tumor diameter in mammography, ultrasonography, contrast-enhanced
      magnetic resonance imaging, and at pathology were retrieved, retrospectively, for
      105 patients eligible for BCT. An analysis of variance technique is employed to
      separate uncertainty at preoperative diagnostic imaging from uncertainty at
      pathology. The random variations are thus calculated independently of the
      systematic deviations, avoiding the necessity to choose a gold standard.
      Moreover, the technique does not require repeat measurements of tumor extent,
      thus allowing the use of data that is obtained in daily clinical practice, while
      avoiding bias due to recollection. The magnitude of the random variations is used
      to determine minimum surgical safety margins and to define the minimum
      significant difference between two measurements of tumor size. The overall random
      variations in the assessment of tumor extent are on the order of 3 mm (1 s.d.)
      with only little differences of about 0.3 mm between the four techniques. The
      dependence of the random variations on tumor size was found significant (p <
      0.05) for mammography (2.7 mm vs 4.2 mm, 1 s.d.) and ultrasonography (2.5 mm vs
      3.8 mm, 1 s.d.) for tumors up to 17 mm compared to those that are larger. A
      minimum surgical safety margin on the order of 5 mm for tumors up to 17 mm and 7
      mm for larger tumors takes the uncertainty in radiological assessment of the
      tumor extent into account effectively in 95% of the performed surgical
      procedures. A minimum difference in largest tumor diameter of 7 mm for tumors up
      to 17 mm and 9 mm for those that are larger indicates a significant (p < 0.05)
      reduction of tumor extent in response to neoadjuvant chemotherapy or hormonal
      therapy. The reproducibility of the assessment of tumor extent at preoperative
      diagnostic imaging is of comparable magnitude to the reproducibility at
      pathology. The uncertainty in the preoperative assessment of tumor extent
      constitutes a large portion (5-7 mm) of the current safety margin in breast
      conserving surgery (10 mm). In monitoring response to neoadjuvant chemotherapy or
      hormonal therapy using repeat imaging before and after treatment, the current
      clinical guidelines may produce approximately 10% false-positive responses for
      tumors between 20 and 30 mm.

PMID- 14655940
TI  - Stress analysis using anatomically realistic coronary tree.
AB  - Plaque rupture with superimposed thrombosis is the main cause of the acute
      coronary syndromes of unstable angina, myocardial infarction, and sudden death.
      Endothelial disruption leading to plaque rupture may relate to mechanical fatigue
      associated with cyclic flexion of plaques. A novel method is proposed to assess
      stress and strain distribution using the finite element (FE) analysis and in vivo
      patient-specific dynamic 3D coronary arterial tree reconstruction from cine
      angiographic images. The local stresses were calculated on the diseased arterial
      wall which was modeled as consisting of a central fibrotic cap subjected to the
      cyclic flexion from cardiac contraction. Various parameters characterizing the
      plaque were chosen including vessel diameter, percentage narrowing, and lesion
      length. According to the FEA simulations, the results show that the smaller
      vessel diameter, greater percentage narrowing, and/or larger lesion size may
      result in higher stress on the plaque cap, with the vessel diameter as the
      dominant factor.

PMID- 14655941
TI  - Independent dosimetric calculation with inclusion of head scatter and MLC
      transmission for IMRT.
AB  - Independent verification of the MU settings and dose calculation of IMRT
      treatment plans is an important step in the IMRT quality assurance (QA)
      procedure. At present, the verification is mainly based on experimental
      measurements, which are time consuming and labor intensive. Although a few
      simplified algorithms have recently been proposed for the independent dose (or
      MU) calculation, head scatter has not been precisely taken into account in all
      these investigations and the dose validation has mainly been limited to the
      central axis. In this work we developed an effective computer algorithm for IMRT
      MU and dose validation. The technique is superior to the currently available
      computer-based MU check systems in that (1) it takes full consideration of the
      head scatter and leaf transmission effects; and (2) it allows a precise dose
      calculation at an arbitrary spatial point instead of merely a point on the
      central axis. In the algorithm the dose at an arbitrary spatial point is
      expressed as a summation of the contributions of primary and scatter radiation
      from all beamlets. Each beamlet is modulated by a dynamic modulation factor
      (DMF), which is determined by the MLC leaf trajectories, the head scatter, the
      jaw positions, and the MLC leaf transmission. A three-source model was used to
      calculate the head scatter distribution for irregular segments shaped by MLC and
      the scatter dose contributions were computed using a modified Clarkson method.
      The system reads in MLC leaf sequence files (or RTP files) generated by the
      Corvus (NOMOS Corporation, Sewickley, PA) inverse planning system and then
      computes the doses at the desired points. The algorithm was applied to study the
      dose distributions of several testing intensity modulated fields and two
      multifield Corvus plans and the results were compared with Corvus plans and
      experimental measurements. The final dose calculations at most spatial points
      agreed with the experimental measurements to within 3% for both the specially
      designed testing fields and the clinical intensity modulated field. Furthermore,
      excellent agreement (mostly within +/- 3.0%) was also found between our
      independent calculation and the ion chamber measurements at both central axis and
      off-axis positions for the multifield Corvus IMRT plans. These results indicate
      that the approach is robust and valuable for routine clinical IMRT plan
      validation.

PMID- 14655942
TI  - Inverse treatment planning by physically constrained minimization of a biological
      objective function.
AB  - In the current state-of-the art of clinical inverse planning, the design of
      clinically acceptable IMRT plans is predominantly based on the optimization of
      physical rather than biological objective functions. A major impetus for this
      trend is the unproven predictive power of radiobiological models, which is
      largely due to the scarcity of data sets for an accurate evaluation of the model
      parameters. On the other hand, these models do capture the currently known dose
      volume effects in tissue dose-response, which should be accounted for in the
      process of optimization. In order to incorporate radiobiological information in
      clinical treatment planning optimization, we propose a hybrid physico-biological
      approach to inverse treatment planning based on the application of a continuous
      penalty function method to the constrained minimization of a biological
      objective. The objective is defined as the weighted sum of normal tissue
      complication probabilities evaluated with the Lyman normal-tissue complication
      probability model. Physical constraints specify the admissible minimum and
      maximum target dose. The continuous penalty function method is then used to find
      an approximate solution of the resulting large-scale constrained minimization
      problem. Plans generated by our approach are compared to ones produced by a
      commercial planning system incorporating physical optimization. The comparisons
      show clinically negligible differences, with the advantage that the hybrid
      technique does not require specifications of any dose-volume constraints to the
      normal tissues. This indicates that the proposed hybrid physico-biological method
      can be used for the generation of clinically acceptable plans.

PMID- 14655943
TI  - Lateral loss and dose discrepancies of multileaf collimator segments in intensity
      modulated radiation therapy.
AB  - In the step-and-shoot technique delivery of intensity modulated radiation therapy
      (IMRT), each static field consists of a number of beamlets, some of which may be
      very small. In this study, we measured the dose characteristics for a range of
      field sizes: 2 x 2 to 12 x 10 cm2 for 6 and 15 MV x rays. For a given field
      length, a number of treatment fields are set up by sequentially increasing the
      field width using a multi leaf collimator. A set of fields is delivered with the
      accelerator operated in the IMRT mode. Using an ion chamber, the output factors
      at 1 cm and 3 cm laterally from a field edge are measured at different depths in
      a solid water phantom. Our results show that with insufficient lateral distance
      in at least one direction, the absorbed dose never reaches the equilibrium
      values, and can be significantly lower for very small field sizes. For example,
      the output factor of the 2 x 2 cm2 field relative to 10 x 10 cm2 at d(max0 is
      0.832 and 0.790 for 6 MV and 15 MV x rays, respectively. Multiple output factor
      curves are obtained for different field lengths and different buildup conditions.
      Thus under nonequilibrium conditions, output factors are critically dependent on
      the field size and the conventional method of determining the equivalent square
      does not apply. Comparison of output factors acquired in the commissioning of the
      accelerator with those measured in the present study under conditions of
      nonequilibrium shows large discrepancies between the two sets of measurements.
      Thus monitor units generated by a treatment planning system using beam data
      commissioned with symmetric fields may be underestimated by > 5%, depending on
      the size and shape of the segments. To facilitate manual MU calculation as an
      independent check in step-and-shoot IMRT, the concept of effective equivalent
      square (EES) is introduced. Using EES, output factors can be calculated using
      existing beam data for fields with asymmetric collimator settings and under
      conditions of lateral disequilibrium.

PMID- 14655944
TI  - A preliminary investigation of local tomography for megavoltage CT imaging.
AB  - We investigate the problem of reconstructing a two-dimensional (2-D) cross
      sectional image of a tumor volume from a set of truncated MV projections that are
      produced by radiation therapy treatment beams. Our proposed approach is
      conceptually distinct from previously investigated approaches in that it utilizes
      a noniterative local tomography reconstruction algorithm. A local tomography
      reconstruction algorithm is implemented and systematically investigated using
      several sets of simulated and experimental MV projection data. We demonstrate
      that the conventional (nonlocal) filtered backprojection reconstruction algorithm
      cannot, in general, accurately reconstruct the edges and boundaries of low
      contrast features from truncated MV projection data. We demonstrate that the
      local tomography algorithm is not adversely affected by projection truncation and
      can reconstruct accurately the boundaries of low-contrast structures within the
      region of interest from truncated MV projections.

PMID- 14655945
TI  - Two-dimensional measurement of photon beam attenuation by the treatment couch and
      immobilization devices using an electronic portal imaging device.
AB  - In our institution, an individualized dosimetric quality assurance protocol for
      intensity modulated radiotherapy (IMRT) is being implemented. This protocol
      includes dosimetric measurements with a fluoroscopic electronic portal imaging
      device (EPID) for all IMRT fields while the patient is being irradiated. For some
      of the first patients enrolled in this protocol, significant beam attenuation by
      (carbon fiber) components of the treatment couch was observed. To study this beam
      attenuation in two-dimensional, EPID images were also acquired in absence of the
      patient, both with and without treatment couch and immobilization devices, as
      positioned during treatment. For treatments of head and neck cancer patients with
      a 6 MV photon beam, attenuation of up to 15% was detected. These findings led to
      the development of new tools and procedures for planning and treatment delivery
      to avoid underdosages in the tumor.

PMID- 14655946
TI  - Real-time inverse planning for Gamma Knife radiosurgery.
AB  - The challenges of real-time Gamma Knife inverse planning are the large number of
      variables involved and the unknown search space a priori. With limited collimator
      sizes, shots have to be heavily overlapped to form a smooth prescription isodose
      line that conforms to the irregular target shape. Such overlaps greatly influence
      the total number of shots per plan, making pre-determination of the total number
      of shots impractical. However, this total number of shots usually defines the
      search space, a pre-requisite for most of the optimization methods. Since each
      shot only covers part of the target, a collection of shots in different locations
      and various collimator sizes selected makes up the global dose distribution that
      conforms to the target. Hence, planning or placing these shots is a combinatorial
      optimization process that is computationally expensive by nature. We have
      previously developed a theory of shot placement and optimization based on
      skeletonization. The real-time inverse planning process, reported in this paper,
      is an expansion and the clinical implementation of this theory. The complete
      planning process consists of two steps. The first step is to determine an optimal
      number of shots including locations and sizes and to assign initial collimator
      size to each of the shots. The second step is to fine-tune the weights using a
      linear-programming technique. The objective function is to minimize the total
      dose to the target boundary (i.e., maximize the dose conformity). Results of an
      ellipsoid test target and ten clinical cases are presented. The clinical cases
      are also compared with physician's manual plans. The target coverage is more than
      99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity
      indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4
      for the inverse plans. All the inverse plans are generated in less than 2 min,
      making real-time inverse planning a reality.

PMID- 14655947
TI  - A dose delivery verification method for conventional and intensity-modulated
      radiation therapy using measured field fluence distributions.
AB  - Treatment verification has been a weak link in external beam radiation therapy.
      As new and more complicated treatment techniques, such as intensity-modulated
      radiation therapy (IMRT), are implemented into clinical practice, verifying the
      accuracy of treatment delivery becomes increasingly important. Existing methods
      for treatment verification are highly labor intensive. We have developed a method
      for verifying the delivery of external beam radiotherapy and implemented the
      methodology into a system consisting of both hardware and software components.
      The system uses grayscale images acquired on the treatment machine from the
      planned treatment beams. From these images, the photon fluence distribution of
      each beam is derived. These measured photon fluence maps are then used as input
      to a separate dose calculation engine to compute the delivered absolute dose and
      the dose distribution in the same patient, assuming that the patient is set up as
      required by the treatment plan. The dose distribution generated from the measured
      fluence maps can then be compared to that of the treatment plan. Software tools,
      such as overlaying isodose curves generated with this method on those imported
      from the plan, dose difference maps, dose difference volume histograms, and three
      dimensional perspective views of the dose differences, have also been developed.
      The system thus provides a means to verify the dose, the dose prescription, and
      the monitor units applied. The potential exists with a suitable electronic portal
      imaging system to reduce the quality assurance efforts, especially for IMRT.

PMID- 14655948
TI  - A method for modifying the image quality parameters of digital radiographic
      images.
AB  - A new computer simulation approach is presented that is capable of modeling
      several varieties of digital radiographic systems by their image quality
      characteristics. In this approach, the resolution and noise characteristics of
      ideal supersampled input images are modified according to input modulation
      transfer functions (MTFs) and noise power spectra (NPS). The modification process
      is separated into two routines-one for modification of the resolution and another
      for modification of the noise characteristics of the input image. The resolution
      modification routine blurs the input image by applying a frequency filter
      described by the input MTF. The resulting blurred image is then reduced to its
      final size to account for the sampling process of the digital system. The noise
      modification routine creates colored noise by filtering the frequency components
      of a white noise spectrum according to the input noise power. This noise is then
      applied to the image by a moving region of interest to account for variations in
      noise due to differences in attenuation. In order to evaluate the efficacy of the
      modification routines, additional routines were developed to assess the
      resolution and noise of digital images. The MTFs measured from the output images
      of the resolution modification routine were within 3% of the input MTF The NPS
      measured from the output images of the noise modification routine were within 2%
      of the input NPS. The findings indicate that the developed modification routines
      provide a good means of simulating the resolution and noise characteristics of
      digital radiographic systems for optimization or processing purposes.

PMID- 14655949
TI  - Micro-angiography for neuro-vascular imaging. I. Experimental evaluation and
      feasibility.
AB  - Minimally invasive image-guided neuro-vascular interventions require very high
      image-resolution and quality, specifically over regions-of-interest (ROI) crucial
      to the procedure. ROI imaging or micro-angiography, allows limited patient
      integral radiation dose while permitting rapid frame transfer of high-resolution
      images. The design and performance of a charge coupled device (CCD) based x-ray
      detector or micro-angiographic camera was assessed for neuro-vascular procedures.
      The detector consists of a 250-microm-thick CsI(Tl) phosphor fiber-optically
      coupled through a 1.8:1 taper to a CCD chip, with an effective image pixel size
      of 50 microm and a frame rate of 5 fps in the 2:1 pixel-binned mode. The
      characteristics of the camera including the modulation transfer function (MTF),
      the noise equivalent quanta, the detective quantum efficiency, observer studies,
      and the effect of geometric magnification were evaluated. The MTF was found to
      have nonzero (1.7%) value at the Nyquist frequency of 10 cycles/mm, while the
      DQE(0) had a value of approximately 55%. All values were measured using head
      equivalent attenuating material in the beam at 80 kVp. Human observer studies
      performed using the 2 Alternative Forced Choice method revealed that iodinated
      vessels with inner diameter of 100 microm and 2 cm in length can be seen with a
      confidence level greater than 75%. The observer studies included a comparison
      with ideal observer performance calculations based on the integral signal to
      noise ratio in the image. Probabilities of visualization of various objects of
      interest in a neuro-intervention, such as stents, were assessed. A geometric
      magnification of 1 was found to be best for imaging under neuro-angiographic
      conditions. The detector appeared to satisfy all the demands of neuro-angiography
      and showed promise as an improvement over existing angiographic detectors.

PMID- 14655950
TI  - Micro-angiography for neuro-vascular imaging. II. Cascade model analysis.
AB  - A micro-angiographic detector was designed and its performance was previously
      tested to evaluate its feasibility as an improvement over current x-ray detectors
      for neuro-interventional imaging. The detector was shown to have a modulation
      transfer function value of about 2% at the Nyquist frequency of 10 cycles/mm and
      a zero frequency detective quantum efficiency [DQE(0)] value of about 55%. An
      assessment of the system was required to evaluate whether the current system was
      performing at its full potential and to determine if any of its components could
      be optimized to further improve the output. For the purpose, in this study, the
      parallel cascade theory was used to analyze the performance of the detector under
      neuro-angiographic conditions by studying the output at the various stages in the
      imaging chain. A simple model for the spread of light in the CsI(Tl) entrance
      phosphor was developed and the resolution degradation due to K-fluorescence
      absorption was calculated. The total gain of the system was found to result in 21
      e(-) (rms) detected at the charge coupled device per absorbed x-ray photon. The
      gain and the spread of quanta in the imaging chain were used to calculate
      theoretically the DQE using the parallel cascade model. The results of the model
      based calculations matched fairly well with the experimental data previously
      obtained. This model was then used to optimize the phosphor thickness for the
      detector. The results showed that the area under the DQE curve had a maximum
      value at 150 microm of CsI(Tl), though when weighted by the squared signal in
      frequency space of a 100-microm-diam iodinated vessel, the integral DQE reached a
      maximum at 250 microm of CsI(Tl). Further, possible locations for gain increase
      in the imaging chain were determined, and the output of the improved system was
      simulated. Thus a theoretical analysis for the micro-angiographic detector was
      performed to better assess its potential.

PMID- 14655951
TI  - Comment on "Dosimetry of the I-Plant Model 3500 iodine-125 brachytherapy source".

PMID- 14655952
TI  - Leveling the high-frequency playing field.

PMID- 14655953
TI  - Norms for the international outcome inventory for hearing aids.
AB  - The International Outcome Inventory for Hearing Aids (IOI-HA) is a seven-item
      survey that was developed for use in research settings to facilitate comparison
      of data across diverse investigations. The inventory also has potential
      applications in clinical evaluation of hearing aid fitting outcomes. This article
      reports the development of norms for the inventory that are suitable for use with
      group data in research applications, and individual data in a clinical setting.
      The normative group was defined as adults fitted bilaterally with analog, single
      channel, single-memory, compression processing, in-the-ear hearing aids. There
      were 154 subjects. Associations between outcomes and demographic variables (e.g.,
      gender, hearing loss, etc.) were explored, and several relationships were seen.
      Based on these data, two sets of norms were derived. The appropriate set will
      depend on the individual's reported subjective hearing problems without
      amplification.

PMID- 14655954
TI  - Acoustic analysis of speech through a hearing aid: perceptual effects of changes
      with two-channel compression.
AB  - Compression amplification significantly alters the acoustic speech signal in
      comparison to linear amplification. The central hypothesis of the present study
      was that the compression settings of a two-channel aid that best preserved the
      acoustic properties of speech compared to linear amplification would yield the
      best perceptual results, and that the compression settings that most altered the
      acoustic properties of speech compared to linear would yield significantly poorer
      speech perception. On the basis of initial acoustic analysis of the test stimuli
      recorded through a hearing aid, two different compression amplification settings
      were chosen for the perceptual study. Participants were 74 adults with mild to
      moderate sensorineural hearing impairment. Overall, the speech perception results
      supported the hypothesis. A further aim of the study was to determine if
      variation in participants' speech perception with compression amplification
      (compared to linear amplification) could be explained by the individual
      characteristics of age, degree of loss, dynamic range, temporal resolution, and
      frequency selectivity; however, no significant relationships were found.

PMID- 14655956
TI  - Neuroelectric correlates of hemispheric asymmetry: spectral discrimination and
      stimulus competition.
AB  - In an effort to explore further the role of the right hemisphere in auditory
      processing, this study utilized brain event-related potentials (ERPs) to
      investigate hemispheric asymmetry for the processing of complex spectral tones.
      Subjects participated in two pitch discrimination tasks, one diotic, the other
      dichotic. ERP components were recorded from 28 electrodes on the scalp and
      analyzed via individual/group average area measurements. Results showed that ERPs
      recorded in response to the dichotic target pairs exhibited a larger P3 area when
      the target tone was presented to the left ear, while the N1 area showed no
      significant difference. ERPs recorded in the diotic condition showed a larger P3
      area and smaller N1 area compared to the dichotic conditions. Finally, all
      experimental tasks showed that topographic hemispheric activation patterns were
      asymmetric to the right hemisphere. Findings support the notion that ERP
      topographic asymmetries may be dependent on specific cognitive task demands
      (e.g., diotic vs. dichotic modes of presentation). In addition, the data suggest
      that the P3 component may better reflect interaural advantages for complex tones
      than the N1 component and may, therefore, be a more sensitive indicator of
      hemispheric specialization.

PMID- 14655955
TI  - Effects of decreased audibility produced by high-pass maskers in younger and
      older adults.
AB  - A recurring problem in aging research is separating the effects of age per se
      from the effects of high-frequency hearing loss. One approach is to present test
      stimuli in the presence of a high-pass masker to control confounding differences
      in high-frequency audibility across age groups. However, there is evidence that
      such maskers may affect older and younger listeners differently. In this study,
      pure-tone thresholds were measured for younger and older listeners in the
      presence of high-pass maskers. The age groups were carefully selected based on
      similar unmasked thresholds at each frequency. Thresholds were measured in quiet
      and in seven masker conditions. Both younger and older listeners showed increased
      threshold shift below the masker passband as the masker level increased. The
      degree of threshold shift was not greater for older versus younger listeners.
      Results suggest that high-pass maskers may be used to reduce high-frequency
      sensitivity differences between younger and older listeners without introducing
      differential masking effects.

PMID- 14655957
TI  - Early detection of ototoxicity using 1/6th-octave steps.
AB  - The National Center for Rehabilitative Auditory Research has developed a protocol
      to provide early identification of ototoxicity for patients receiving ototoxic
      medications. The initial work involved patients with relatively good high
      frequency hearing and resulted in the use of an individualized, sensitive
      frequency range separated by 1/6th-octave intervals. This protocol tested pure
      tone frequencies at 1/6th-octave steps above 9 kHz, but only conventional
      audiometric frequencies were tested below 9 kHz. More recently, the testing
      protocol was expanded to include 1/6th-octave testing below 9 kHz. The primary
      question of interest was to determine whether adding 1/6th-octave test
      frequencies below 9 kHz would increase the ototoxicity detection rate for
      patients with poorer hearing. Results indicated 76 of the 210 (36.2%) ears that
      demonstrated initial ototoxic hearing change would have been missed or detected
      later if only conventional frequency testing was conducted.Therefore, for
      individuals with poorer hearing, expanding the use of the 1/6th-octave test
      protocol provides earlier identification of ototoxicity.

PMID- 14655958
TI  - The role of the trial judge in a criminal jury trial.

PMID- 14655959
TI  - The Cresta Run: a uniquely evolving tradition.
AB  - The Cresta Run is a unique toboggan run and exists in only one place in the
      world, namely, St. Moritz, Switzerland. The height of the resort is over 6,000
      feet (1828 metres). Therefore there is a diminution of oxygen content in the air.
      Normally it takes from three to seven days for a person from lower habitat
      altitudes, visiting the resort, to become fully acclimatized if they are to be
      involved in energetic competitive sport. The age and fitness of the toboggan
      rider is a factor. The Cresta Run takes place each year and has, since its
      inception under the auspices of the St Moritz Tobogganing Club, been built from
      virgin snow to a formula determined by a brilliant 22-year-old Swiss
      geometrician, Peter Bonorand, who devised the first Run in 1884. Using his
      exceptional mathematical knowledge to determine a course from St. Moritz to
      Celerina, he drew up plans and drawings for the first Cresta Run. The Run
      therefore is constructed to a known formula and it is significant that in over
      115 years the times on the Run have only improved on average by a few tenths of a
      second progressively each year despite improvements to riding equipment. Since
      the Run's inception in 1885 there has always been an element of danger, but
      accidents have invariably occurred on the section of the Run that comprises the
      competition course between the start line and the finish line. During the past
      few seasons, an increasing number of accidents have taken place after the finish
      line. The problem is short-term blackout while riding (Reader, 1978). There is
      now a need to investigate what changes have been made or have evolved to cause
      this. However, certain immutable facts have remained constant and these must be
      identified and then considered in the context of recent changes as a result of
      improvements in equipment. Considerable improvements have been made over the past
      25 years to safety helmets. These are the result of different materials, their
      suitability and ease of manufacture, particularly with regard to the full-face
      type helmet. The full-face helmet could be a significant contributing factor to
      the problem of accidents, particularly after the finish line, on the Cresta Run.

PMID- 14655960
TI  - The creation of inter-ethnic images for studies in applied psychology.
AB  - The facial transformation programme, is an integral part of the computerised
      three-dimensional facial reconstruction system, employed at the University of
      Glasgow for forensic and historical cases. It was applied to the creation of
      inter-ethnic images for use in studies to assess the response of various groups
      to facial appearance in the assessment of racial stereotyping. We initially
      acquired a three-dimensional facial image from a young black (Negroid) male
      volunteer, using our optical laser scanning system. This image was then used as a
      template over a Caucasian skull to produce a reconstruction using facial criteria
      applicable to white (Caucasian) males. The other image used was that of the
      facial template of the black male. A commercially available electronic identikit
      system, E-FIT was then used to add appropriate hair styles and open eyes to both
      images. In addition, on the 'Caucasian reconstruction' we were able to reduce the
      contrast and lighting on the face. This was relatively straightforward as we were
      using greyscale images rather than colour. The shape of the nose and lips on the
      white male were also altered to be more in keeping with Caucasoid average
      measurements. The resulting images were shown to a group of second-year clinical
      psychology students and their responses are discussed. Similar images may also be
      used in studies of racial stereotyping in different categories of professionals
      such as police, prison personnel, probation officers, social workers, potential
      employers, doctors, and others, in order to assess the response to individuals by
      facial appearance.

PMID- 14655961
TI  - Fatal pulmonary thromboembolism in Singapore: has anything changed?
AB  - A previous study of fatal pulmonary thromboembolism (PE) during a five-year
      period (1989-1993) in Singapore found a low post-mortem prevalence of fatal PE
      (1.05%). The present study investigated cases of fatal PE among 10,097 coroner's
      post-mortems conducted between 1994 and 1998 at the Centre for Forensic Medicine,
      Health Sciences Authority, Singapore, and compared the results with the previous
      study. There were 130 cases of fatal PE, representing a post-mortem prevalence of
      1.29%. This is comparable to the previous study but is lower than most other
      published series from other countries. There was a shift towards younger
      subjects, with the modal age group being 40 to 49 years, compared with 70 to 79
      years previously. A large proportion of subjects had risk factors for PE, with
      42.3%, 23.8% and 11.5% having had a history of surgery, trauma or malignancy
      respectively. After the onset of immobility or trauma, 50% of subjects developed
      PE in the first seven days and 76.8% in the first two weeks. PE was not suspected
      as the cause of death in 74.6% of cases under medical care. The incidence of
      fatal PE in Singapore remains low. However, a large proportion of cases continue
      to be unsuspected as the cause of death. It would appear that, on the whole, a
      correct clinical diagnosis of fatal pulmonary thromboembolism remains largely
      elusive.

PMID- 14655962
TI  - Lies ... damned lies ... and suicide statistics! 'There are three kinds of lies:
      lies, damned lies and statistics'. Statement attributed to Disraeli in Mark
      Twain's Autobiography (1924).
AB  - In the absence of any measurable outcome in psychiatry, suicide is now regarded
      as an outcome measure in Mental Health Services. The National Service Framework
      (NSF) has set the reduction of the suicide rate by 20 per cent over the next
      seven years as a national priority. This article will examine how reliable
      suicide is as an outcome measure.

PMID- 14655963
TI  - Can shaking alone cause fatal brain injury? A biomechanical assessment of the
      Duhaime shaken baby syndrome model.
AB  - A biomechanical model of a one-month old baby was designed and tested by Duhaime
      and co-workers in 1987 in an attempt to assess the biomechanics of the shaken
      baby syndrome (SBS). The study implied that pure shaking alone cannot cause fatal
      head injuries, a factor which has been applied in criminal courts. In an attempt
      to test the validity of the model a preliminary study was undertaken in which a
      replica was constructed and tested. The broad description of the design and
      construction of the Duhaime model allowed for variations and therefore
      uncertainties in its reproduction. It was postulated therefore that differences
      in certain parameters may increase angular head accelerations. To further
      investigate this observation, an adjustable replica model was developed and
      tested. The results indicated that certain parameter changes in the model did in
      fact lead to an increase in angular head acceleration. When these parameter
      changes were combined and an injurious shake pattern was employed, using maximum
      physical effort, the angular head acceleration results exceeded the original
      Duhaime et al. (1987) results and spanned two scaled tolerance limits for
      concussion. Additionally, literature suggests that the tolerance limits used to
      assess the shaking simulation results in the original study may not be reliable.
      Results from our study were closer to the internal head injury, subdural
      haematoma, tolerance limits. A series of end point impacts were identified in the
      shake cycles, therefore, an impact-based head injury measure (Head Injury
      Criterion - HIC) was utilized to assess their severity. Seven out of ten tests
      conducted resulted in HIC values exceeding the tolerance limits (critical load
      value, Sturtz, 1980) suggested for children. At this present stage the authors
      conclude that it cannot be categorically stated, from a biomechanical
      perspective, that pure shaking cannot cause fatal head injuries in an infant.
      Parameters identified in this study require further investigation to assess the
      accuracy of simulation and increase the biofidelity of the models before further
      conclusions can be drawn. There must now be sufficient doubt in the reliability
      of the Duhaime et al. (1987) biomechanical study to warrant the exclusion of such
      testimony in cases of suspected shaken baby syndrome.

PMID- 14655965
TI  - First ever admission to medium security.
AB  - This paper describes the characteristics of a group of patients admitted to a
      Medium Security Unit over the course of a ten-year period who had never
      previously had any form of psychiatric inpatient care. We used a computerised
      data base to gain detailed information. The control group was made up of patients
      admitted to the same hospital over the study period who had been psychiatric
      inpatients before but not in medium secure conditions. We found that the patients
      from the first ever admission group were generally older and that the numbers had
      increased over the ten-year period. Their average length of stay was shorter. The
      most common diagnosis for all patients was schizophrenia. The findings suggest
      that there is a place for secure provision in the treatment of first episode
      psychosis, especially if the initial contact is through a penal institution.

PMID- 14655964
TI  - Does insomnia in prison improve with time? Prospective study among remanded
      prisoners using the Pittsburgh Sleep Quality Index.
AB  - Insomnia is a frequent health problem in prison, but little is known about its
      severity and duration. The objective was to find out whether subjective sleep
      quality improves during time and which factors influence improvement. Fifty-two
      randomly chosen prisoners complaining of insomnia at the Geneva remand prison
      were interviewed (T1) and followed up ten days (T2) and two months (T3) later.
      They received hypnotics habitually prescribed by prison physicians
      (benzodiazepines, chloralhydrate, zolpidem). After ten days 40 patients were
      still in prison and agreed to participate and after two months 16 prisoners could
      be re-evaluated. Total Pittsburgh Sleep Quality Index (PSQI) scores at T1 were
      12.3 +/- 4.7. At T2 and T3, PSQI scores improved significantly, whereas General
      Health Questionnaire (GHQ) scores and conditions of imprisonment were similar.
      Only 12.5% of patients at T2, and 6.25% at T3, were 'good sleepers' (PSQI scores
      =/< 5). Cocaine users and prisoners with a healthy lifestyle reported the
      greatest improvement of PSQI scores. Our study shows that significant improvement
      of PSQI scores takes place in the first one to two weeks. However, in spite of
      regular drug treatment during the following weeks, PSQI scores persisted at a
      clinically significant level two months later. Drug treatment in prison only
      partially improves insomnia.

PMID- 14655966
TI  - Electrocution in South Delhi: a retrospective study.
AB  - One hundred and fifty three unselected autopsy cases of electrocution received
      from South Delhi were studied during the period 1996-2001. Data for the study was
      gathered from autopsy reports and hospital records. The cases represented
      approximately 1.98% of all autopsy cases received from South Delhi at the All
      India Institute of Medical Sciences, New Delhi (India). Data was analysed with
      regard to the age and sex of the victim, season of the year, site of the body,
      time of day, place of occurrence and presence of entry and exit wounds on the
      body. Death occurred at the scene of the fatal event in 150 cases and three cases
      died in hospital. Three cases showed no electric burn marks on the body; the
      cause of death in one of these cases was polytrauma due to a fall from a height
      and one case had committed suicide.

PMID- 14655967
TI  - Left aortic arch with right-sided descending aorta associated with sudden
      neonatal death: a case report.
AB  - We present the case of a 26-day-old female in whom left aortic arch with right
      sided descending aorta occurred. The previously healthy newborn baby was found
      dead on her bed. This anomaly is very uncommon and its clinical presentation as
      sudden death is also exceptional with only a few cases having been reported in
      the literature. The pathological findings and embryological origins of this
      malformation, so-called 'circumflex aorta' are discussed. The pertinent
      literature is reviewed.

PMID- 14655968
TI  - Identification of severely incinerated human remains: the need for a cooperative
      approach between forensic specialities. A case report.
AB  - Positive identification of incinerated human remains can be a perplexing problem,
      especially when there is no genetic material remaining for DNA analysis. This
      paper illustrates the importance of a multi-disciplinary approach to the
      identification of such remains, and explores the processes involved in the
      various effects of heat upon human bone and teeth, and the implications this has
      for positive identification. A case study is presented to illustrate the various
      problems encountered and the importance of discovering comprehensive ante-mortem
      records of the deceased. It is submitted that forensic odontologists and
      anthropologists be included in the body recovery process, both to maximise the
      recovery of evidence, and to ensure that all possible avenues for positive
      identification are explored, so as to avoid the need to rely upon the less robust
      method of circumstantial identification.

PMID- 14655970
TI  - Nursing knowledge is acquired through a variety of sources.

PMID- 14655971
TI  - Nursing terminology.

PMID- 14655972
TI  - The power of partnerships: a model for practice, education, and research.

PMID- 14655973
TI  - Dynamics of hope in HIV/AIDS affected people: an exploration of significant
      others' experiences.
AB  - Hope is an important protective phenomenon in human life, particularly given that
      long-lasting despair or hopelessness may threaten human existence. However,
      previous knowledge on the topic related to people affected by HIV/AIDS is scant.
      The purpose of this study was to explore the dynamics of hope in significant
      others of people living with HIV/AIDS and persons living with HIV (PLWH) or AIDS
      (PLWA) from the perspective of significant others in Finland. Eleven interviews
      were conducted with six significant others. The data were analyzed using the
      grounded theory method. The dynamics of hope, as it emerged from the data, is
      constructed of three main elements: hope, despair, hopelessness, and their
      reciprocal relationships. An alternating balance between hope, despair, and
      hopelessness based on the factors contributing to them emerged as central in the
      dynamics of hope. The dynamics of hope are closely connected to the basic process
      of searching for one's own way with HIV/AIDS, in becoming HIV-positive, and
      living with HIV/AIDS. In significant others, the dynamics of hope are closely
      connected to the basic process of HIV, changing from abstract to concrete in a
      relationship with a PLWH/PLWA.

PMID- 14655974
TI  - The measurement of delirium: review of scales.
AB  - This review describes the characteristics and evaluates the psychometric
      qualities (process of testing and the results) of thirteen delirium instruments.
      Delirium instruments differ in goal (diagnosis, screening symptoms severity),
      type of data on which the rating is based (observation, interview or test of
      patients), the rater qualities required, the number of items and the rating time
      needed. Most instruments are based on the Diagnostic Statistical Manual criteria
      and measure signs and symptoms as described by these criteria. Reliability of
      delirium instruments shows good to excellent results. Validity of the delirium
      instruments is overall fair to good. Differences exist, however, in the degree to
      which reliability and validity were tested and the quality of the testing
      procedures. Most instruments are not further developed and tested after the
      initial study. Conclusion of this review is that most delirium instruments show
      promising results but need further testing. Testing is needed in different
      samples and on a broader range of aspects with regard to reliability and
      validity. Much emphasis should be given to the procedures used in future studies.
      Ease of use is an aspect of testing that is so far not taken into account,
      however, is important for use of instruments in clinical practice. A minority of
      instruments can be seen as "ready to use" instruments meaning well tested in more
      than one sample with good results. For screening high-risk, elderly hospitalized
      patients, the NEECHAM Confusion Scale and the Delirium Observation Screening
      Scale are recommended. The Confusion Assessment Method is the best diagnostic
      tool and the Delirium Rating Scale shows best results in screening symptom
      severity. For ICU patients the CAM-ICU is recommended. The MDAS is well tested in
      cancer patients. Nurses, however, have not yet tested the DRS and MDAS in
      practice.

PMID- 14655975
TI  - Evolving out of violence: an application of the Transtheoretical Model of
      Behavioral Change.
AB  - Ending violent relationships can be a difficult and lengthy process. Women use a
      variety of coping activities, with change generally proceeding in a non-linear
      direction. Nurses may not recognize this behavior pattern and may expect more
      from a woman experiencing violence than she is currently able or willing to
      achieve, thereby hampering change. Studying behavioral patterns of change by
      women experiencing intimate partner violence (IPV) was explored through the
      stages and processes of change conceptually defined within the Transtheoretical
      Model (TTM). Using a Delphi technique, the TTM was tested with four White,
      professional women reporting past IPV. Original stages and processes of change
      were reviewed and modified to fit the woman's experience. Research findings
      supported the TTM as a useful guide to alert health care professionals of the
      readiness level of women experiencing IPV and determine effective interventions.

PMID- 14655976
TI  - Comparison of U.S., Canadian, and Australian participants' performance on the
      Algase Wandering Scale-Version 2 (AWS-V2).
AB  - Although wandering in dementia is seen in various cultures, cross-cultural
      comparisons have not been reported. We examined wandering in residents of long
      term care settings (LTCs) in three English-speaking countries (n = 96, America; n
      = 42, Canada; n = 13, Australia) using the Algase Wandering Scale-Version 2 (AWS
      V2). Participants differed by country on age and medical diagnosis. The Americans
      were significantly older; the Canadians had a greater rate of Alzheimer's disease
      (AD). In one-way ANOVAs, AWS-V2 ratings from nurse aides revealed significant
      differences in the AWS-V2 and three subscales (spatial disorientation, attention
      shifting, eloping behavior), but not for two others (persistent walking,
      shadowing). Where significant, Canadians had consistently lower ratings than
      others. Post-hoc analyses by age of participants failed to reveal significant
      differences. However, participants with AD had significantly lower AWS-V2 scores
      than those with mixed-type dementia. Lower MMSE score predicted higher AWS-V2,
      spatial disorientation, and eloping behavior. Post-hoc analyses of respondent
      characteristics revealed no significant differences on AWS-V2 or subscales by
      frequency of attending dementia classes and level of experience with dementia.
      Thus the nature of wandering in these three countries is not substantially
      different. However, variations in care environments may contribute to differences
      in attention shifting. Further, limited sample size, particularly among
      Australians and Canadians, make findings tentative.

PMID- 14655977
TI  - Research process in the health sciences: a focus on methods.
AB  - Research in the health sciences is becoming increasingly challenging as data and
      methods advance in complexity. This article was written to provide an overview of
      the research process for complex and intricate projects, with a focus on methods.
      The insights regarding structuring and managing research projects are intended to
      guide researchers through all phases of the research process. Our key suggestions
      include the following: (1) conceptual and methodological complexity must be
      balanced, (2) skilled project managers and statisticians are needed, and can be
      rewarded for their contributions to projects in part through authorship, and (3)
      grants involving multiple investigators present problems related in part to the
      abstruseness of integrated methods and so require special solutions for effective
      management. Overall, we conclude that researchers are rewarded in a variety of
      ways when they remain focused on the original study aims, keep methods simple,
      utilize skilled staff, and engage in strategic planning.

PMID- 14655978
TI  - Management of monocular congenital cataracts.

PMID- 14655979
TI  - Treatment outcomes of congenital monocular cataracts: the effects of surgical
      timing and patching compliance.

PMID- 14655980
TI  - Management outcome in prethreshold retinopathy of prematurity.
AB  - PURPOSE: To evaluate the success of and timing for intervention in retinopathy of
      prematurity (ROP). PATIENTS AND METHODS: Eighty-two eyes of 50 children with
      stage 3 ROP were divided into two groups based on severity. Cryotherapy or laser
      therapy was performed soon after the detection of threshold stage in the first
      group of 40 eyes and at a prethreshold stage in the second group of 42 eyes. The
      patients were observed from 4 months to 2 years and regression or progression was
      noted. Unfavorable outcomes including macular and disc drag and the progression
      of ROP to stages 4 and 5 were correlated with birth weight, gestational age, age
      at threshold, and age at intervention. RESULTS: Regression of ROP occurred in 75
      (91.46%) of the eyes. An overall unfavorable outcome occurred in 14 (17.07%) of
      the eyes, 11 of which reached threshold during the critical period of 37 to 39
      postconceptional weeks of age. Of the cases (n = 14) with an unfavorable outcome,
      9 eyes (22.5%) were in the group treated in the threshold stage (n = 40) and 5
      eyes (11.9%) were in the group treated at a prethreshold stage (n = 42). The mean
      birth weight, gestational age, age at threshold, and age at intervention in the
      favorable and unfavorable outcome groups were 953.2 +/- 2.19 g and 1,059.57 +/-
      2.62 g, 28.63 +/- 2.03 weeks and 28.36 +/- 1.98 weeks, 38.04 +/- 2.13 weeks and
      37.71 +/- 1.13 weeks, and 38.32 +/- 2.34 weeks and 38.25 +/- 1.05 weeks,
      respectively. CONCLUSION: Early intervention at a prethreshold stage of ROP or at
      a younger postconceptional age (ie, younger than 37 weeks) may decrease the
      incidence of an unfavorable outcome.

PMID- 14655981
TI  - Uveitis in childhood.
AB  - PURPOSE: To review the etiologic factors and complications of uveitis in patients
      younger than 16 years. PATIENTS AND METHODS: Between January 1989 and December
      1999 in the Department of Ophthalmology of Hacettepe University School of
      Medicine, 219 patients were diagnosed or observed as having pediatric uveitis.
      After complete ocular and physical examinations, routine and specific laboratory
      and radiologic investigations were performed. Medical or surgical treatment was
      employed when necessary. RESULTS: Of the 219 patients, 112 were girls, with a
      mean age of 7.4 +/- 4.2 years, and 107 were boys, with a mean age of 8.3 +/- 3.4
      years. In 24.2% of the cases, no etiologic factor could be ascertained; these
      cases comprised the idiopathic group. Among the remaining cases, the most common
      etiologies were toxoplasmosis, juvenile rheumatoid arthritis (JRA), pars
      planitis, Behcet's disease, and Fuchs' heterochromic iridocyclitis. Anatomically,
      anterior uveitis was the most common form. The mean follow-up time was 37 +/- 6.2
      months. Complications for which surgical treatment was employed were identified
      in 71 eyes (20.9%), most of which were due to JRA, pars planitis, or Behcet's
      disease. CONCLUSION: Uveitis in childhood may be idiopathic or most commonly due
      to toxoplasmosis, JRA, and pars planitis. Due to inflammation itself or to
      prolonged therapy especially with corticosteroids, pediatric uveitis entities
      (mostly JRA, pars planitis, or Behcet's disease) may result in complications
      necessitating a surgical approach.

PMID- 14655982
TI  - The moving dynamic random dot stereosize test: validity and repeatability.
AB  - PURPOSE: We have developed a new test suitable for measuring stereopsis in young
      children and individuals with communication difficulties. It consists of a
      drifting, computer-generated red and green, dynamic random dot, disparate shape.
      The motion direction is indicated by the subject (subjective response) or by a
      naive observer judging the eye movements of the subject (objective response).
      Disparity is maintained at 616 sec arc and the dependent variable is the angular
      subtense of the target, which varies from 11 degrees to 11 ft. In this study,
      precision (ie, measuring repeatability and objective-subjective agreement) and
      validity were assessed. SUBJECTS AND METHODS: Sixteen subjects with normal vision
      participated in the repeatability study and 10 in the validity studies. A two
      up/one-down, 2 alternative forced choice staircase procedure was used to measure
      objective and subjective threshold on two occasions with a 1-week separation.
      Sensitivity for detecting anisometropia was estimated with simulated
      anisometropia (0 to 3 D) and by comparison with the Randot test. Sensitivity for
      detecting amblyopia or strabismus was tested in 10 subjects. RESULTS: Subjective
      repeatability was 0.31 log units (2 levels of the test) and objective
      repeatability was 0.49 log units (3.2 levels of the test). The test was able to
      detect 2.0 D of simulated anisometropia in 8 of 10 cases (above the 95%
      confidence interval). None of the amblyopic subjects demonstrated stereopsis.
      CONCLUSION: This test of dynamic global stereopsis has potential as a clinical or
      screening tool for anisometropia, amblyopia, and strabismus.

PMID- 14655983
TI  - Topical mydriatic and cycloplegic spray for Chinese children.
AB  - PURPOSE: To assess the efficacy and tolerance of mydriatic and cycloplegic spray
      versus drops for Chinese children. METHODS: The effects of the spray
      (cyclopentolate 0.25%, phenylephrine 0.625%, and tropicamide 0.5%) and the drops
      (cyclopentolate 1%, phenylephrine 0.5%, and tropicamide 0.5%) were evaluated in
      29 children (58 eyes) in two separate sessions. There was a 1-week period between
      the applications of the spray and the drops. Dilated pupil size and refraction
      after cycloplegia were the primary outcome variables used to assess the efficacy.
      A subjective discomfort score was used to assess acceptance of the spray and the
      drops. RESULTS: The mean age of the study population was 4.33 +/- 1.39 years
      (range, 3 to 8 years). The mean pupil size was 6.9 mm for the spray and 6.6 mm
      for the drops. The spray appeared to be slightly more effective than the drops,
      with a mean difference of 0.3 mm that was statistically significant (P = .001,
      two-tailed t test). No statistically significant difference in cycloplegic
      response was found between the spray and the drops (P = .535, two-tailed t test).
      Administration of the spray caused less discomfort than did administration of the
      drops (P < .001, Wilcoxon signed-rank test). CONCLUSIONS: The spray system
      appears to be clinically equivalent to the drops for achieving effective pupil
      dilation and cycloplegia, even in a population with dark irides such as ours.
      Tolerability and acceptance improved because the spray was applied to the closed
      eyelids.

PMID- 14655984
TI  - Macular hole without hemorrhages and shaken baby syndrome: practical medicolegal
      documentation of children's eye trauma.

PMID- 14655985
TI  - Bilateral orbital granulocytic sarcoma as a presenting sign of acute myeloid
      leukemia.

PMID- 14655986
TI  - Atypical presentation of bone marrow transplant retinopathy.

PMID- 14655987
TI  - Mouse parvovirus: survival of the fittest.

PMID- 14655988
TI  - ACLAM position statement on animal experimentation.

PMID- 14655989
TI  - Sleep mechanisms in health and disease.
AB  - Excess sleepiness, abnormal sleep patterns, non-restorative sleep, and fatigue
      are becoming increasingly pervasive in modern society. Identifying substances and
      mechanisms that modulate sleep and vigilance during health and disease is a
      critical prelude to eventual development of interventions to prevent or alleviate
      these disabling problems. A unified interdisciplinary approach that includes
      neurophysiology, neuroanatomy, neurochemistry, and molecular biology will promote
      elucidation of the complex biology of sleep. Integration of basic sleep
      physiology with modern genetic techniques will eventually lead to identification
      of specific genes and substances involved in regulation of various facets of
      sleep. The review presented here highlights recent progress in defining the
      anatomy and physiology of sleep-wake regulatory systems, delineating the role of
      homeostatic and circadian process in regulating sleep and wakefulness, and
      establishing the relationship of sleep and sleep disorders to other medical
      conditions. Particular emphasis is placed on reviewing the interactions between
      sleep, infectious challenge, and host defense response, and on identifying
      mechanisms that contribute to variation in sleep patterns among various strains
      of inbred mice.

PMID- 14655990
TI  - Reducing exposure to laboratory animal allergens.
AB  - Laboratory animal allergy is a serious health problem. We examined several
      possible allergen-reducing strategies that might be effective in the working
      mouse room. Ambient allergen concentrations were measured when mice were
      maintained under several conditions: conventional housing versus ventilated cage
      racks operated under negative or positive pressure. We found that housing mice in
      ventilated cages operated under negative pressure and using ventilated changing
      tables reduced ambient mouse allergen (Mus m 1) concentrations tenfold, compared
      with values when mice were housed in conventional caging and using a conventional
      (non-ventilated) changing table. Housing mice in positively pressurized cages
      versus conventional cages did not reduce ambient allergen values. Cleaning mouse
      rooms at an accelerated frequency also did not reduce ambient Mus m 1
      concentration. We also quantified ambient allergen values in several areas of The
      Jackson Laboratory. A facility-wide survey of Mus m 1 concentrations indicated
      that allergen concentrations were undetectable in control areas, but ranged from
      a mean (+/- SEM) 0.11 +/- 0.02 ng/m3 to 5.40 +/- 0.30 ng/m3 in mouse rooms with
      different cage types. The percentage of animal caretakers reporting allergy
      symptoms correlated significantly with ambient allergen concentrations: 12.9%
      reported symptoms in the rooms with the lowest allergen concentration (0.14 +/-
      0.02 ng/m3), but 45.9% reported symptoms in rooms with the highest concentration
      (2.3 +/- 0.4 ng/m3). These data indicate that existing technology can
      significantly reduce exposure to laboratory animal allergens and improve the
      health of animal caretakers.

PMID- 14655991
TI  - Left ventricular end-diastolic pressure-volume relationship in septic rats with
      open thorax.
AB  - To estimate changes in compliance, we evaluated the effects of sepsis on the end
      diastolic pressure-volume relationship (EDPVR) in the left ventricle of rats that
      had undergone an open thorax procedure. Sepsis was induced in male Wistar
      Hannover rats (n = 7; 240 to 270 g) by intraperitoneal administration of a slurry
      of cecal contents; control rats (n = 7) were given 5% dextrose only. On the third
      day after induction of sepsis, left ventricular (LV) pressure and LV dimensions
      were recorded simultaneously in animals of both groups. Using a micromanometer
      and ultrasonic crystals, measurements were obtained at baseline and during the
      increase of afterload. Blood samples were taken for determination of complete
      blood count, white blood cell differential count, and lactate concentration, and
      for bacteriologic examination. Septic rats lost weight, and developed changes in
      body temperature, ascites, and abscesses in the abdominal and thoracic cavities,
      gram-negative bacteremia, and increase in heart rate. On the third day after
      induction of sepsis, LV EDPVR decreased, compared with that in the control rats
      (regression coefficients: control group, 8.41 to 23.95; sepsis group, 3.94 to
      7.92). Myocardial compliance in the left ventricle increased on the third day of
      sepsis in the open-thorax rat model, as evidenced by the downward shift of LV
      EDPVR in rats with sepsis, compared with controls.

PMID- 14655993
TI  - Mouse embryo yield and viability after euthanasia by CO2 inhalation or cervical
      dislocation.
AB  - Efficient production of transgenic mice requires high yields of viable, healthy
      embryos. Cervical dislocation (without prior anesthesia) rather than CO2
      inhalation as a means of euthanasia has been justified on the basis of the
      increased yield of viable ova, but controlled studies have not directly supported
      this contention. The American Veterinary Medical Association (AVMA) and Canadian
      Council on Animal Care (CCAC) Guides, and respective Institutional Animal Care
      and Use Committees (IACUC) have supported the use of CO2 as a preferred, humane
      method. The study reported here was undertaken to determine the relative yields
      of viable embryos from mice euthanized either by inhalation of 100% CO2 or by
      cervical dislocation. Inbred and hybrid mouse strains, representative of common
      strains used in genetic engineering experimentation included C57BL/6, FVB/N, and
      B6SJLF1. There was no difference in the embryo yields in comparisons using the
      two methods of euthanasia (P = 0.534). Decisions regarding the method of
      euthanasia can be made on the basis of criteria other than those associated with
      embryo yield and viability.

PMID- 14655992
TI  - Adoptive transfer of splenocytes in SCID mice implicates CD4+ T cells in
      apoptosis and epithelial proliferation associated with Helicobacter pylori
      induced gastritis.
AB  - Helicobacter pylori causes severe, rapidly progressive gastritis in severe
      combined immunodeficient (SCID) mouse recipients of congenic splenocytes. The H.
      pylori-infected and uninfected C57BL/6J and recipient SCID mice were evaluated to
      detect CD4+ and CD8+ T cells, B cells, apoptotic epithelial cells, and epithelial
      cell proliferation at postinoculation weeks 5, 6, 8, and 12. Serum was evaluated
      for anti-H. pylori IgG and IgM. In all H. pylori-infected mice, gastric CD4+ cell
      scores were increased, compared with scores for uninfected controls. Recipient
      mice differed, however, according to the source of the transferred CD4+ cells.
      The CD4+ cell scores for recipients of splenocytes from H. pylori-infected
      (immune) donors were indistinguishable from those for wild-type donor mice at all
      time points. In contrast, gastric mucosal CD4+ cell scores did not become
      significantly high until two weeks after transfer (postinoculation week 6) in
      recipients of cells from uninfected (naive) donors. Gastric epithelial apoptosis
      and the gastric epithelial proliferation zone were significantly (P < 0.05)
      increased in infected recipient and donor, compared with non-recipient and
      uninfected mice at postinoculation week 12. Results indicated that CD4 cells are
      sensitized in vivo and migrate to the gastric mucosa where they induce gastritis
      in response to H. pylori antigens. Influx of CD4 cells and gastritis are
      correlated with epithelial proliferation and apoptosis, and suggest that CD4
      dependent H. pylori gastritis leads to epithelial damage with attendant
      proliferative and metaplastic responses.

PMID- 14655994
TI  - Susceptibility of zebrafish (Danio rerio) to a model pathogen, spring viremia of
      carp virus.
AB  - To improve our understanding of the genetic basis of fish disease, we developed a
      pathogen model, using zebrafish (Danio rerio) and spring virema of carp virus
      (SVCV). Replicate groups of 10 fish were acclimated to 20 or 24 degrees C, then
      were exposed to SVCV concentrations of 10(3) to 10(5) plaque-forming units per
      milliliter (PFU/ml) of water and observed daily. In a second trial, fish were
      acclimated to 15 degrees C, and replicate groups of 10 fish were exposed to SVCV
      at a concentration of 10(5) PFU/ml; however, the temperature was raised 1 degrees
      C/wk. Moribund fish were collected for histologic examination, and dead fish were
      assayed for virus by use of cell culture and reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis. Mortality exceeded 50% in fish exposed to 10(5)
      PFU of SVCV/ml at the lower temperatures. Clinical signs of disease became
      evident seven days after viral exposure and were observed most consistently in
      fish of the 10(5) PFU/ml groups. Affected zebrafish were anorectic and listless,
      with epidermal petechial hemorrhages followed by death. Use of plaque assays and
      RT-PCR analysis confirmed presence of SVCV at titers > or = 10(4) PFU/g of
      tissue. Histologic lesions included multifocal brachial necrosis and
      melanomacrophage proliferation in gills, liver, and kidneys. These results
      indicate that zebrafish are susceptible to infection by SVCV under conditions
      that mimic a natural route of exposure.

PMID- 14655995
TI  - Modified two-step model for studying the inflammatory response during myocardial
      ischemia and reperfusion in mice.
AB  - Studies of myocardial ischemia-reperfusion (MI-R) in the mouse can be
      accomplished by use of reversible ligation of the left interventricular branch
      artery (LIB). To study interactions of coagulation, inflammation, and reperfusion
      injury, the model should not be influenced by effects of the surgery. In existing
      closed-thorax mouse models, the release of inflammatory factors attributable to
      surgical intervention could be separated from the release resulting from
      induction of MI-R. In these models, the final myocardial injury was induced by
      reversible closure of the LIB several days after preparative surgery that
      included median thoracotomy. In an attempt to develop a less invasive procedure
      to approach the LIB, we replaced median thoracotomy with lateral thoracotomy.
      After this procedure, body weight was regained within four days, and on days 9 to
      11 after the preparative surgery, cytokine values were back to baseline. During
      one hour of ischemia, mean arterial pressure (MAP) remained at 78 +/- 2 mmHg.
      After induction of reperfusion, MAP was 67 +/- 4 mmHg, indicating better
      perfusion pressure of myocardial tissue at the microcirculatory level than that
      in simple open-thorax models. Electrocardiographic recording revealed transient
      ST elevation indicating reversible transmural ischemia and reperfusion. Evans
      blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining visualized the extent
      of area of infarction (AOI) and area at risk (AAR). The procedure-related
      mortality was 13%, which compared well with published data from median
      thoracotomy studies. We conclude that our new model provides stable near
      physiologic hemodynamics and allows study of the inflammatory response resulting
      from MI-R, with low procedure-related mortality.

PMID- 14655996
TI  - Androgen-dependent atypical fibromas spontaneously arising in the skin of
      Djungarian hamsters (Phodopus sungorus).
AB  - Spontaneous atypical fibromas that arose in the thoracoabdominal skin of one aged
      female and 31 aged male Djungarian hamsters (Phodopus sungorus) were examined
      histologically, immunohistochemically, and ultrastructurally. The normal skin
      from both sexes obtained at various intervals until the age of 12 months was
      examined, as were the tumors. These tumors were composed of ganglion cell-like
      (GL) cells that had one or two ovoid nuclei, basophilic foamy cytoplasm, and
      various amount of collagen fibers between the cells. The tumor cells had positive
      reaction to vimentin and androgen receptor (AR); the stromal collagen fibers
      reacted positively with the antibody against collagen type I or III.
      Ultrastructurally, the tumor cells had abundant rough endoplasmic reticulum in
      the cytoplasm. On the other hand, small nests of the cells mimicking tumor GL
      cells were present in the dermal layer to the panniculus of the normal
      thoracoabdominal skin of adult males, but were seldom found in adult females. The
      morphologic and immunohistochemical features of these tumor GL cells were
      basically similar to those of normal skin GL cells, although the former had a
      certain degree of atypia. These results suggest that atypical skin fibroma in the
      Djungarian hamster is an androgen-dependent tumor and originates from skin GL
      cells.

PMID- 14655997
TI  - Estrous cycle and ovarian changes in a rat mammary carcinogenesis model after
      irradiation, tamoxifen chemoprevention, and aging.
AB  - PURPOSE: Variation in the effects of selective estrogen receptor modulators
      (SERMs) on the estrous cycle and reproductive organs during aging could play an
      important role in the observed heterogeneity of tamoxifen chemoprevention
      efficacy against breast cancer. METHODS: Of the 1,022 female Sprague Dawley rats
      enrolled in a long-term tamoxifen chemoprevention study, 87 were randomly chosen
      from four groups (irradiated, irradiated and tamoxifen treated, tamoxifen
      treated, and control). Vaginal smears were evaluated for determination of cycle
      stage, and vaginal pathologic changes. Correlation with the histologic features
      of reproductive tissues in 43 animals was made. RESULTS: More tamoxifen-treated
      (21.9%; 7/32) rats had irregular cycling than did control (9%; 3/23) rats.
      Ovarian granulosa cell hyperplasia was present in 50% (3/6) of tamoxifen-treated
      rats, and 20% (2/10) of control rats. Endometrial-type cells (ETCs) were present
      only in tamoxifen-treated (tamoxifen alone 6.25% [2/32]) and tamoxifen/ radiation
      treated (28.6% [4/14]) rats. CONCLUSION: The modified Papanicolaou stain used
      here provided excellent morphologic detail for evaluating the estrous cycle in
      rodents. Tamoxifen altered vaginal cytologic and ovarian histologic features
      during aging. Results indicated that tamoxifen had direct and indirect effects on
      the reproductive tract, causing disturbance of the estrous cycle, shedding of
      ETCs, and promoting granulosa cell hyperplasia. Understanding of the
      heterogeneous response to tamoxifen chemoprevention during aging in rodents may
      provide important insights into the basis for tamoxifen chemoprevention failures
      in humans.

PMID- 14655998
TI  - XY female marmoset (Callithrix jacchus).
AB  - A marmoset (Callithrix jacchus) with atypical external genitalia was
      phenotypically and genetically characterized. Testosterone concentration
      correlated with that of female marmosets. Externally, there was only one opening
      for the urethra. Internal genitalia were characteristic of those of female
      marmosets, and consisted of ovaries, with follicles in various developmental
      stages, and uterus. Microscopically, a normal vaginal structure was found. An
      XX/XY chimerism and high steroid hormone values are normally found in common
      marmosets. Genetic analysis was used for in vivo determination of sex. The Y
      linked zinc finger protein gene (ZFY) last intron, and sex-determining region Y
      gene (SRY) exon were found by use of polymerase chain reaction and posterior
      sequencing analyses, indicating that this marmoset had Y-linked chromosome
      sequences. Normal SRY exons can, therefore, be associated with female internal
      sexual organs in marmosets; this may be the first XY female described in non
      human primates.

PMID- 14655999
TI  - Abdominal cysticercosis in a rhesus macaque (Macaca mulatta).
AB  - A mid-abdominal mass was discovered during routine physical examination of a
      rhesus macaque (Macaca mulatta). Further diagnostics and exploratory laparotomy
      were performed, revealing a fluid-filled cyst attached to the caudal free margin
      of the greater omentum. Formation and pulsatile movement of white-colored
      circumferential bands within the wall of the cyst were observed during surgery.
      The cyst was removed and later was dissected. The discovery of a single
      invaginated scolex identified the cyst as a cysticercus. The location and
      characteristics of the cysticercus were consistent with the larval form of Taenia
      hydatigena.

PMID- 14656000
TI  - Avipox sp. in a colony of gray-crowned rosy finches (Leucosticte tephrocotis).
AB  - Members of a wild-caught colony of 16 gray-crowned rosy finches (Leucosticte
      tephrocotis) were presented with dermal and mucosal lesions, anorexia,
      emaciation, lethargy, and sudden death. Lesions included dermatitis,
      conjunctivitis, and glossitis. Skin scrapings from and bacterial culture of
      dermal lesions yielded Staphylococcus aureus and Candida albicans. Necropsy and
      histologic examination revealed characteristic epidermal and mucosal pox lesions,
      with the presence of characteristic Bollinger body intracellular inclusions.
      Electron microscopy (EM) provided confirmation of pox virus infection. This
      epornitic resulted in the death or euthanasia of 12 birds (75% morbidity and
      associated mortality) and was brought to conclusion through culling of affected
      birds. The source of infection remains unknown, although multiple modes of
      introduction exist. Similar epornitics may be prevented through indoor, species
      specific housing, and quarantine. Vaccination and antiparasitic treatment may
      reduce the risk of disease spread.

PMID- 14656001
TI  - EGFR and wingless signaling pathways interact to specify the ocellar pattern in
      Drosophila.
AB  - This report shows that the Wingless signaling pathway regulates the expression of
      epidermal growth factor receptor (EGFR) in Drosophila. This pathway specifies
      cell fate during head development. Blocking wingless signaling upregulates
      Drosophila epidermal growth factor receptor (DER) activity and expands its
      expression domains in the eye primordium. Moreover, ectopic expression of
      wingless inhibits DER signaling and dramatically restricts its expression domain.
      This study suggests a novel role of wingless in specifying the Drosophila dorsal
      head via blocking vein expression in this region.

PMID- 14656002
TI  - Distribution patterns of TGF-alpha, laminin and fibronectin and their
      relationship with folliculogenesis in rat ovary.
AB  - Many growth factors are considered to be involved in regulatory functions in the
      ovary. Specific factors mediate local cell-cell interactions in relation to
      follicle development. As a result of the complexity of the estrous cycles in
      experimental models, it is not easy to determine the role of a growth factor such
      as transforming growth factor alpha (TGF-alpha) in the system. Moreover, little
      is known about possible interactions of TGF-alpha and laminin and fibronectin in
      basement membranes during estrous cycles in relation to follicle development.
      Therefore, the present study was designed to investigate distribution patterns of
      TGF-alpha, laminin and fibronectin and their possible roles during follicle
      maturation in normal rat ovary. Ovaries were obtained from 6 adult virgin female
      rats and fixed in buffered neutral formalin. TGF-alpha, laminin, and fibronectin
      distribution patterns were evaluated using 5-7-microm-thick serial sections using
      the immunoperoxidase method. It was found that TGF-alpha was predominantly
      localised in nuclei of oocytes. Varying amounts of TGF-alpha were found in
      granulosa cells and interstitial thecal cells which form follicles. In addition,
      laminin and fibronectin were found predominantly in vascular walls, outer layers
      of granulosa cells and basement membranes of cuboidal/columnar surface epithelium
      of rat ovary. Therefore, we suggest that TGF-alpha is involved in follicular
      maturation. Moreover, because laminin was found to be present in between
      parenchymal follicle cell layers, we suggest that they were attached to
      supportive stromal cells by fibronectin. As TGF-alpha is associated with
      follicles and their relationship with the extracellular matrix, TGF-alpha may
      also induce formation of basement membranes which contains laminin and
      fibronectin components.

PMID- 14656003
TI  - Immunohistochemical localization of amylin in human pancreas, thyroid, pituitary
      and their tumors.
AB  - The aim of the present study was to investigate immunohistochemically expression
      of amylin, a 37 amino acid peptide, cosecreted with insulin by beta cells in
      pancreatic islets in 12 non-tumorous pancreatic tissues, 22 pancreatic islet
      tumors, 14 non-tumorous thyroids, 14 medullary carcinomas of the thyroid, 10 non
      tumorous pituitaries and 50 pituitary adenomas including 10 amyloid-forming
      prolactin-cell adenomas using the streptavidin-biotin-peroxidase complex method.
      Amylin was expressed in non-tumorous pancreatic islets but not in non-tumorous
      thyroids and pituitaries. Since amylin plays an important role in amyloid
      formation in pancreatic islets, those tumor types were selected to study which
      may produce amyloid. Amylin was widely expressed in one insulin producing beta
      cell tumor. Few tumor cells were immunopositive in 8 islet-cell tumors and in 5
      medullary thyroid carcinomas. Immunostaining was not found in pituitary adenomas,
      including those which produced amyloid. It can be concluded that amylin is not a
      satisfactory immunohistochemical marker to identify pancreatic islet tumors,
      medullary thyroid carcinomas and pituitary adenomas.

PMID- 14656004
TI  - Glycoconjugates of the gastric mucosa in cold-treated chipmunks.
AB  - During seasonal hibernation, there is reduced gastrointestinal activity, but
      relatively little is known of the physiology involved. In the present
      experimental study, male Korean chipmunks (Tamias sibiricus barberi) were
      maintained in cold conditions (6 degrees C) for 3, 5 or 9 months to mimic
      conditions occurring during seasonal hibernation. Changes in the composition of
      glycoconjugates (Gcs) of the gastric mucosa were determined after cold-treatment.
      Cold-treated chipmunks, in comparison with warm control animals, revealed a
      thinner layer of Gcs on the free surface gastric epithelium with reduced depth of
      their pits. Cold-treated chipmunks showed similar staining patterns and lectin
      affinity for Gcs as compared with warm control animals. After long-term cold
      treatment, reduction in the amounts of Gcs were more severe in gastric pit
      epithelium and glandular mucous cells than in the free surface gastric
      epithelium. A significant reduction in immunostaining of nitric oxide synthase
      (NOS) was also observed in chipmunks after long-term cold-treatment. The changes
      in Gcs and NOS staining patterns may be interpreted in relation with a continued
      but reduced functioning of the gastric mucosa throughout hibernation. However,
      the findings in the present experimental model for hibernation, which shows
      significant changes in Gcs and NOS staining patterns, need to be demonstrated
      during seasonal hibernation in the wild.

PMID- 14656005
TI  - Review article--involvement of gastric APUD cells in chronic renal failure.
AB  - Uremia leads to a number of metabolic and hormonal disorders induced by renal
      failure with definite biological and clinical sequels. Most frequently,
      alimentary disorders are the first to appear, followed by symptoms from other
      organs and systems. The gastrointestinal tract is a site of synthesis of many
      compounds that have hormonal or hormonal-like biological activity. These
      substances are produced by highly-specialised receptor-effector cells, that are
      dispersed in the gastrointestinal mucosa and classified as APUD cells. The
      present review is an attempt to make a synthesis of current opinions and views
      concerning the effect of homeostatic dysfunction of the kidneys on the morphology
      and action of APUD cells in the stomach.

PMID- 14656006
TI  - Expression of glucosamine trisaccharides on the rat uterine surface is altered by
      clomiphene citrate. III. Relationship with implantation regimes and pregnancy.
AB  - The present study further elucidates the complex effects of a commonly-prescribed
      fertility drug upon a target organ in an animal model. In the human condition,
      its effects are rarely observed without the influence of endogenous ovarian
      hormones. The aim of the study was to investigate how the administration of a
      single dose of clomiphene citrate (CC) given prior to an implantation-priming
      sequence of ovarian hormones would affect the expression of surface
      oligosaccharides and membrane architecture of uterine epithelium. Ovariectomized
      rats were given a single dose of either 0.25 mg or 1.25 mg of CC prior to a
      hormone-priming regime of progesterone (P4) for 3 days with a single additional
      administration of oestradiol 17beta (E2) on day 3. Animals were killed 24 h after
      final treatment. Uterine tissue was labelled with the lectin Phytolacca americana
      conjugated with avidin, subsequently labelled with biotinylated ferritin and
      prepared for transmission electron microscopy. Results indicate that CC, when
      administered prior to the implantation hormone-priming regime, is able to act as
      a super oestrogen and upregulates expression of oligosaccharides on the plasma
      membrane surface and increases the density and length of microvilli on the
      surface of the cells when compared with other treatment regimes. Understanding of
      the effects of CC at the uterine level at the time of implantation enables
      manipulation of uterine receptivity to control fertility and to improve the
      outcome of assisted reproductive procedures.

PMID- 14656007
TI  - Cytochemical study of spermiogenesis and mature spermatozoa in the lizard
      Tropidurus itambere (Reptilia, Squamata).
AB  - The present study was undertaken to detect essential components of spermatozoa by
      ultrastructural and cytochemical analyses of testis and epididymis of the lizard
      Tropidurus itambere at different points of its annual reproductive cycle.
      Cytochemical investigations of spermiogenesis have not been performed so far in
      Squamata and are scarce for lower vertebrates. Essential components are: 1)
      polysaccharides, identified by PAS staining, abundantly present in Sertoli cell
      elongations, acrosomal vesicles and the acrosome of sperm cells; 2)
      glycoconjugate variations, labeled by different lectins and used to investigate
      cell modifications during spermiogenesis and found in mature spermatozoa in the
      female's seminal receptacle; 3) basic proteins, present in large quantities in
      spermatozoa in the subacrosomal cone, the pericentriolar material, the midpiece
      dense bodies, the peripheral fibers of the axoneme, and the fibrous sheath of the
      flagellum; 4) the final reaction product of acid phosphatase activity in several
      stages of acrosome development, specifically in the clear zone and epinuclear
      electron-lucent region of spermatozoal acrosomes, as well as in very active
      lysosomes found during the quiescent period of the reproductive cycle; 5) lipids,
      abundantly present in the cytoplasm of Leydig cells during the quiescent period.
      The cytochemical methods show that the ultrastructurally complex acrosome is also
      biochemically heterogeneous, with specific layers rich in glycoproteins, basic
      proteins or acid phosphatase. These different components may play a role during
      sperm penetration into the ovule. Basic proteins are largely responsible for
      structures surrounding the axoneme to provide resistance to the flagellum. In the
      quiescent period, acid phosphatase activity is involved in the elimination of
      superfluous sperm cells, whereas lipids in Leydig cells are used for hormone
      synthesis which starts at this time point to initiate a new reproductive cycle.
      Variations in lectin staining revealing glycoconjugates show that spermatozoa
      undergo post-testicular maturation up to their storage in the female.

PMID- 14656008
TI  - Differential diagnosis of amyloid and amyloidosis by histochemical methods of
      Romhanyi and Wright.

PMID- 14656009
TI  - Significance of Romhanyi's scientific work to study amyloid and amyloid-related
      proteins in animals.

PMID- 14656010
TI  - Polarization optical analysis of amyloid deposits with various topo-optical
      reactions.

PMID- 14656011
TI  - Romhanyi's staining methods applied to tissue-isolated amyloid fibrils.

PMID- 14656012
TI  - Severe problems in diagnosing amyloid diseases.

PMID- 14656013
TI  - Senile amyloidoses--diseases of increasing importance.

PMID- 14656014
TI  - Structure and formation of amyloid fibrils.

PMID- 14656015
TI  - Where are we standing in homocysteine research?

PMID- 14656016
TI  - DACH-LIGA homocystein (german, austrian and swiss homocysteine society):
      consensus paper on the rational clinical use of homocysteine, folic acid and B
      vitamins in cardiovascular and thrombotic diseases: guidelines and
      recommendations.
AB  - About half of all deaths are due to cardiovascular disease and its complications.
      The economic burden on society and the healthcare system from cardiovascular
      disability, complications, and treatments is huge and getting larger in the
      rapidly aging populations of developed countries. As conventional risk factors
      fail to account for part of the cases, homocysteine, a "new" risk factor, is
      being viewed with mounting interest. Homocysteine is a sulfur-containing
      intermediate product in the normal metabolism of methionine, an essential amino
      acid. Folic acid, vitamin B12, and vitamin B6 deficiencies and reduced enzyme
      activities inhibit the breakdown of homocysteine, thus increasing the
      intracellular homocysteine concentration. Numerous retrospective and prospective
      studies have consistently found an independent relationship between mild
      hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting
      at a plasma homocysteine concentration of approximately 10 micromol/l, the risk
      increase follows a linear dose-response relationship with no specific threshold
      level. Hyperhomocysteinemia as an independent risk factor for cardiovascular
      disease is thought to be responsible for about 10% of total risk. Elevated plasma
      homocysteine levels (>12 micromol/l; moderate hyperhomocysteinemia) are
      considered cytotoxic and are found in 5 to 10% of the general population and in
      up to 40% of patients with vascular disease. Additional risk factors (smoking,
      arterial hypertension, diabetes, and hyperlipidemia) may additively or, by
      interacting with homocysteine, synergistically (and hence over-proportionally)
      increase overall risk. Hyperhomocysteinemia is associated with alterations in
      vascular morphology, loss of endothelial anti-thrombotic function, and induction
      of a procoagulant environment. Most known forms of damage or injury are due to
      homocysteine-mediated oxidative stress. Especially when acting as direct or
      indirect antagonists of cofactors and enzyme activities, numerous agents, drugs,
      diseases, and lifestyle factors have an impact on homocysteine metabolism. Folic
      acid deficiency is considered the most common cause of hyperhomocysteinemia. An
      adequate intake of at least 400 microg of folate per day is difficult to maintain
      even with a balanced diet, and high-risk groups often find it impossible to meet
      these folate requirements. Based on the available evidence, there is an
      increasing call for the diagnosis and treatment of elevated homocysteine levels
      in high-risk individuals in general and patients with manifest vascular disease
      in particular. Subjects of both populations should first have a baseline
      homocysteine assay. Except where manifestations are already present,
      intervention, if any, should be guided by the severity of hyperhomocysteinemia.
      Consistent with other working parties and consensus groups, we recommend a target
      plasma homocysteine level of <10 micromol/l. Based on various calculation models,
      reduction of elevated plasma homocysteine concentrations may theoretically
      prevent up to 25% of cardiovascular events. Supplementation is inexpensive,
      potentially effective, and devoid of adverse effects and, therefore, has an
      exceptionally favorable benefit/risk ratio. The results of ongoing randomized
      controlled intervention trials must be available before screening for, and
      treatment of, hyperhomocysteinemia can be recommended for the apparently healthy
      general population.

PMID- 14656017
TI  - Hyperhomocysteinaemia as a risk factor for venous thrombosis: an update of the
      current evidence.
AB  - Classical homocystinuria is associated with arterial vascular diseases and venous
      thrombosis. In the last decade, many studies, including some prospective studies,
      have been published indicating that moderate hyperhomocysteinaemia is also a risk
      factor for venous thrombosis. The 677C>T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild
      hyperhomocysteinaemia. Recent metaanalyses show an elevated risk of venous
      thrombosis for subjects with the TT-genotype. Based on the concept of 'Mendelian
      randomisation', this observation supports the hypothesis that
      hyperhomocysteinaemia is a causal risk factor for venous thrombosis. The results
      of one homocysteine-lowering trial regarding venous thrombosis are awaited at the
      end of 2003. In this paper the current evidence for hyperhomocysteinaemia as a
      risk factor for venous thrombosis is being discussed.

PMID- 14656018
TI  - Does homocysteine cause hypertension?
AB  - Several studies, some population-based, have plasma homocysteine levels linked to
      blood pressure, especially systolic pressure. In one large and carefully
      conducted epidemiological study, each 5 micromol/l increase in plasma
      homocysteine was associated with an increase in systolic and diastolic blood
      pressure of 0.7/0.5 mmHg in men and 1.2/0.7 mmHg in women, which was independent
      of renal function and B vitamin status. In addition, observations that
      homocysteine-lowering therapies with folic acid-based treatments have been
      followed by decreases in blood pressure raise the possibility that the link
      between homocysteine and blood pressure is causal, which is important since
      homocysteine levels can easily be lowered by folic acid-based regimens.
      Mechanisms that could explain the relationship between homocysteine and blood
      pressure include homocysteine-induced arteriolar constriction, renal dysfunction
      and increased sodium reabsorption, and increased arterial stiffness. However,
      there is only circumstantial evidence that these mechanisms are operative in
      humans. In addition, confounding by subtle renal dysfunction or by unmeasured
      dietary and lifestyle factors cannot be excluded as an explanation for the
      association between homocysteine and blood pressure. At present, therefore, the
      hypothesis that homocysteine increases blood pressure must be considered
      unproven. Ongoing large intervention studies with homocysteine-lowering vitamins
      may show whether blood pressure is indeed lowered by these vitamins, whether the
      blood pressure decrease, if any, is explained by the decrease in homocysteine
      levels, and whether a vitamin treatment-associated decrease in cardiovascular
      morbidity, if any, is explained by the decrease in blood pressure.

PMID- 14656019
TI  - Homocysteine metabolism in renal disease.
AB  - Hyperhomocysteinemia, a new cardiovascular risk factor, occurs in 85-100% of
      patients with end-stage renal disease. The exact mechanism by which renal
      function is linked to plasma homocysteine has not been definitively established.
      There is reasonably good clinical evidence that hyperhomocysteinemia in itself
      does not cause renal insufficiency. Two, not mutually exclusive, hypotheses are
      that in renal failure: i) homocysteine disposal is impaired in the kidneys
      themselves and ii) extra-renal homocysteine metabolism is defective, possibly due
      to uremic toxins. Several methods have been applied to investigate kidney and
      whole-body sulfur amino acid metabolism in healthy subjects and in patients with
      different degrees of renal failure. Arteriovenous extraction studies have not
      found a significant homocysteine disposal in the human kidney. Methods to study
      whole-body homocysteine metabolism have included measurement of plasma
      metabolites, calculation of plasma homocysteine elimination after oral loading
      and the use of stable isotope techniques with methionine tracers. The results
      implicate a decreased homocysteine clearance instead of an increased production
      as the cause of hyperhomocysteinemia in renal failure, but the exact site of the
      impaired clearance remains controversial.

PMID- 14656020
TI  - Hyperhomocysteinemia and B-vitamin deficiencies in infants and children.
AB  - Measurement of total homocysteine (tHcy) in healthy and diseased children has
      documented the utility of this marker in pediatric research and diagnostics. This
      article focuses on novel data obtained in infants, children and adolescents, with
      emphasis on cobalamin status in infants. In children, determinants of plasma tHcy
      are similar to those established in adults, and include age, gender, nutrition, B
      vitamin status, and some drugs interfering with B-vitamin function. In infants
      (age < 1 year), tHcy is moderately elevated and related to serum cobalamin,
      whereas in older children and throughout childhood, plasma tHcy is low (about 60%
      of adult levels), and folate status becomes a strong tHcy determinant. As in
      adults, hyperhomocysteinemia in childhood is a risk factor for stroke, and folate
      responsive hyperhomocysteinemia has been detected in children with renal failure.
      tHcy seems to be a sensitive indicator of folate deficiency in children on a poor
      diet, in HIV-infected children, and in children treated with anti-folate drugs.
      In children at increased risk of cobalamin deficiency, which includes children
      born to vegetarian mothers or children in developing countries on a poor diet,
      tHcy and methylmalonic acid are responsive indicators of a deficiency state. In
      newborns and infants born to mothers with an adequate nutrition, there are
      consistent observations of low cobalamin, elevated tHcy and methylmalonic acid,
      and reduction of both metabolites by cobalamin supplementation. These data have
      raised the question whether cobalamin deficiency may be widespread and undetected
      in babies born to non-vegetarian women on a Westernized diet.

PMID- 14656021
TI  - The role of genetic factors in the development of hyperhomocysteinemia.
AB  - Moderate hyperhomocysteinemia has been identified as a new independent risk
      factor for cardiovascular and neurodegenerative diseases. This fact has produced
      interest in the study of genetic variants involved in homocysteine metabolism and
      its relationship to pathogenesis. Recently, more than 15 different genes were
      studied for their relationship to plasma homocysteine levels. We determined the
      influence of genetic variants in five genes (5,10-methylenetetrahydrofolate
      reductase (MTHFR) 677C --> T, serine hydroxymethyltransferase (SHMT) 1420C --> T,
      thymidylate synthase (TS) 2R --> 3R, catechol-O-methyltransferase (COMT) 1947G -
      > A and transcobalamin (TC) 776C --> G) on plasma homocysteine, folic acid and
      parameters of vitamin B12 metabolism in 111 vegetarians (mean age: 46 +/- 15
      years) and 118 healthy seniors (mean age: 82 +/- 6.5 years). Median homocysteine
      concentration in plasma was significantly influenced by the MTHFR genotypes in
      both populations. In the vegetarians the median homocysteine level was increased
      by 8 micromol/l in individuals homozygous for the mutation as compared to wild
      type or heterozygous genotypes (20.4 micromol/l vs. 12.9 and 12.7 micromol/l,
      respectively). This unexpected increase was observed although the folate levels
      were in medium to elevated ranges. Our results suggest that vegetarians have a
      higher demand for folate to neutralize the genotype effect. Preclinical vitamin
      B12 deficiency in vegetarians may be the cause for disturbed remethylation and
      folate trap. Plasma homocysteine was not significantly influenced by the SHMT,
      TS, COMT and TC mutations. In addition, for the TC mutation a trend toward
      cellular vitamin B12 deficiency was observed. The methylmalonic acid (MMA) levels
      were slightly elevated and the holotranscobalamin-II (holoTC-II) levels
      decreased. In the vegetarian group a significant relationship between the COMT
      genotype and holoTC-II concentration in plasma was determined, whereas the high
      activity COMT genotype (G/G) resulted in increased levels (35 micromol/l vs. 21
      micromol/l for heterozygous and low activity genotypes). The MMA levels were
      inversely correlated to holoTC-II concentrations. In conclusion, the study on
      vegetarians and seniors documents interesting lifestyle-genotype interactions.
      Although the TC and COMT mutations influence cellular vitamin B12 metabolism,
      this effect did not result in overt homocysteine elevation.

PMID- 14656022
TI  - New basis of the neurotrophic action of vitamin B12.
AB  - Over the last few years we have reproduced all of the key morphological and
      biochemical features of human subacute combined degeneration in the central
      nervous system and peripheral nervous system of rats made cobalamin-deficient by
      means of total gastrectomy or a chronic cobalamin-deficient diet. We have also
      recently clarified the pathogenesis of experimental subacute combined
      degeneration induced in the rat by cobalamin deprivation. The results of our
      studies strongly support the notion that cobalamin plays a pivotal role in
      regulating the balance of the network of cytokines and growth factors in the
      central nervous system of the rat. We have demonstrated that cobalamin tightly
      regulates the central nervous system synthesis and/or the cerebrospinal fluid
      level of two cytokines, tumor necrosis factor-alpha and interleukin-6, and a
      growth factor, epidermal growth factor. Of these neuroactive agents, one, tumor
      necrosis factor-alpha, is neurotoxic, whereas the others are neurotrophic.
      Therefore, it becomes clear that cobalamin-deficient central neuropathy is caused
      not by the withdrawal of the vitamin, but reflects a locally increased production
      of neurotoxic agents, combined with the locally decreased production of
      neurotrophic agents.

PMID- 14656023
TI  - Hyperhomocysteinemia and immune activation.
AB  - Hyperhomocysteinemia is an established risk factor for atherosclerosis,
      thrombosis and other vascular diseases. Homocysteine auto-oxidation is considered
      to be crucially involved in the pathogenesis of these diseases. However, the
      question remains to be elucidated whether vitamin deficiency and homocysteine
      accumulation are causal for disease development or rather comprise a secondary
      phenomenon. Most diseases accompanied by hyperhomocysteinemia are also associated
      with ongoing activation of the immune system. In vitro experiments show
      homocysteine to accumulate in stimulated peripheral blood mononuclear cells. In
      patients with coronary heart disease, with rheumatoid arthritis and in patients
      with dementia, an association between cellular immune activation and homocysteine
      metabolism is found. Homocysteine concentrations not only correlate inversely
      with folate concentrations, they also show a positive relationship with
      concentrations of immune activation markers like neopterin. Moreover, in patients
      with various kinds of dementia, increased concentrations of serum peroxides,
      homocysteine and neopterin correlate with each other. Studies support a role of
      immune system activation in the development of hyperhomocysteinemia. Stimulation
      and proliferation of immune cells may lead to the production of reactive oxygen
      species that may oxidize antioxidants and oxidation-sensitive B-vitamins. An
      enhanced demand for antioxidants as well as folate and vitamin B12 may develop,
      together with hyperhomocysteinemia, despite sufficient dietary intake.

PMID- 14656024
TI  - Interactions of homocysteine, nitric oxide, folate and radicals in the
      progressively damaged endothelium.
AB  - The endothelium exerts fundamental control over vascular tone, and injury to the
      endothelium followed by dysfunction is an early key event preceding manifestation
      of vessel pathology. Both elevated plasma homocysteine and low folate status have
      been identified as major and independent risk factors for atherosclerosis and
      have stirred an enormous and still increasing interest. The damaging effects of
      hyperhomocysteinemia on endothelial function are, at least in part, reversible
      through folate supplementation. Because of the inverse relationship between
      plasma folate and homocysteine levels, however, it is difficult to discriminate
      between their respective effects. Endothelial dysfunction refers mainly to
      reduced bioavailability of nitric oxide (NO), which is involved in
      homocysteinemediated vascular damage. Accumulating evidence further suggests that
      radical oxygen species are fundamentally involved in hyperhomocysteinemia. NO
      production is determined by cofactors such as tetrahydrobiopterin, which is
      oxidized and depleted in conditions of oxidant stress by peroxynitrite.
      Deficiency of tetrahydrofolate contributes to uncoupling, turning the NO synthase
      into a superoxide radical-producing enzyme. It appears that progression of
      vascular disease is likely to determine the multiple interactions between
      homocysteine, NO, oxygen radicals and folate. Folate has only recently been found
      to exert direct anti-oxidative effects and contribute to restoration of impaired
      NO metabolism. Understanding of the complex interactions between homocysteine,
      radicals, NO and folate offers promising perspectives in the individual treatment
      of vascular disease. Thus, preventive and therapeutic strategies may require a
      more distinct approach and better discrimination of target groups for greatest
      possible efficacy.

PMID- 14656025
TI  - Influence of hyperhomocysteinemia on the cellular redox state--impact on
      homocysteine-induced endothelial dysfunction.
AB  - Hyperhomocysteinemia is an independent risk factor for the development of
      atherosclerosis. An increasing body of evidence has implicated oxidative stress
      as being contributory to homocysteine's deleterious effects on the vasculature.
      Elevated levels of homocysteine may lead to increased generation of superoxide by
      a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent,
      by an increase in the chemical oxidation of homocysteine and other aminothiols in
      the circulation. The resultant increase in superoxide levels is further amplified
      by homocysteine-dependent alterations in the function of cellular antioxidant
      enzymes such as cellular glutathione peroxidase or extracellular superoxide
      dismutase. One direct clinical consequence of elevated vascular superoxide levels
      is the inactivation of the vasorelaxant messenger nitric oxide, leading to
      endothelial dysfunction. Scavenging of superoxide anion by either superoxide
      dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial
      dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings
      incubated with homocysteine. Similarly, homocysteine-induced endothelial
      dysfunction is also reversed by increasing the concentration of the endogenous
      antioxidant glutathione or overexpressing cellular glutathione peroxidase in
      animal models of mild hyperhomocysteinemia. Taken together, these findings
      strongly suggest that the adverse vascular effects of homocysteine are at least
      partly mediated by oxidative inactivation of nitric oxide.

PMID- 14656026
TI  - Homocysteine-thiolactone and S-nitroso-homocysteine mediate incorporation of
      homocysteine into protein in humans.
AB  - Indirect pathways, involving homocysteine (Hcy)-thiolactone and S-nitroso-Hcy,
      allow incorporation of Hcy into protein. Hcy-thiolactone, synthesized by
      methionyl-tRNA synthetase in all organisms investigated, including human,
      modifies proteins post-translationally by forming adducts in which Hcy is linked
      by amide bonds to epsilon-amino group of protein lysine residues. S-Nitroso-Hcy,
      synthesized in human vascular endothelial cells, is incorporated translationally
      into peptide bonds in protein at positions normally occupied by methionine. Hcy-N
      hemoglobin and Hcy-N-albumin constitute a major pool of Hcy in human blood. Hcy
      thiolactone is present in human plasma. Modification with Hcy-thiolactone leads
      to protein damage. Hcy-thiolactone is detoxified by Hcy-thiolactonase/paraoxonase
      present in a subset of high-density lipoprotein particles in humans.

PMID- 14656027
TI  - Association of asymmetric dimethylarginine and endothelial dysfunction.
AB  - There is abundant evidence that the endothelium plays a crucial role in the
      maintenance of vascular tone and structure. One of the major endothelium-derived
      vasoactive mediators is nitric oxide (NO), which has been characterized as an
      "endogenous anti-atherosclerotic molecule". Synthesis of NO can be selectively
      inhibited by guanidino-substituted analogs of L-arginine, which act as
      competitive inhibitors at the active site of the enzyme. One such analog is
      asymmetric dimethylarginine (ADMA), a compound that has been found in human
      plasma and urine and exerts the activity of an endogenous inhibitor of NO
      synthase. In contrast to ADMA, its regioisomer symmetric dimethylarginine (SDMA)
      does not inhibit NO synthase. The methyl groups contained within the
      dimethylarginine molecules are derived from S-adenosylmethionine, an intermediate
      in the homocysteine/methionine pathway. There is experimental evidence that
      homocysteine may affect endothelium-dependent vascular function by increasing the
      formation of ADMA. Both ADMA and SDMA are eliminated from the body by renal
      excretion. In addition, the metabolism of ADMA, but not SDMA, occurs via
      hydrolytic degradation to citrulline and dimethylamine by the enzyme
      dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies
      suggest that ADMA inhibits vascular NO elaboration at concentrations found in
      pathophysiological conditions (i.e., 3-15 microM). ADMA likely acts as an
      autocrine regulator of endothelial NO synthase activity. When rabbits are placed
      on a diet enriched with 1% cholesterol, ADMA levels are increased within 4 weeks
      of dietary intervention as compared to control animals. Elevated plasma
      concentrations of ADMA are also present in hypercholesterolemic and hypertensive
      patients, in patients with chronic heart failure, and in other patient groups at
      high risk of developing cardiovascular disease. Elevation of ADMA induces
      dysfunction of the endothelium, which becomes clinically evident by impaired
      endothelium-dependent vasodilation, hyperaggregability of platelets, and enhanced
      monocyte adhesion. Recent prospective studies suggest that endothelial
      dysfunction indicates an increased risk of future cardiovascular events. In line
      with these observations, we and others found evidence that ADMA is a novel
      cardiovascular risk factor.

PMID- 14656028
TI  - Genetic determinants of folate and vitamin B12 metabolism: a common pathway in
      neural tube defect and Down syndrome?
AB  - One-carbon metabolism is under the influence of folate, vitamin B12 and genetic
      polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C --> T and 1298
      A --> C), of methionine synthase (MTR 2756 C --> G), methionine synthase
      reductase (MTRR 66 A --> G) and transcobalamin (TCN 776 C --> G). The
      pathogenesis of neural tube defect (NTD) may be related to this metabolism. The
      influence of the MTHFR 677 C --> T polymorphism reported in The Netherlands and
      Ireland can be questioned in southern Italy, France and Great Britain. MTRR,
      combined with a low level of vitamin B12, increases the risk of NTD and of having
      a child with NTD in Canada, while TCN 776 GG and MTRR 66 GG mutated genotypes
      associated with the MTHFR 677 CC wild-type are predictors of NTD cases in Sicily.
      Down syndrome (DS) is due to a failure of normal chromosomal segregation during
      meiosis, possibly related to one-carbon metabolism. MTHFR 677 C --> T and MTRR 66
      A --> G polymorphisms are associated with a greater risk of having a child with
      DS in North America, Ireland and The Netherlands. In contrast, MTHFR 677 C --> T
      has no influence on DS risk in France and Sicily, while homocysteine and MTR 2756
      AG/GG genotypes are predictors of DS risk in Sicily. In conclusion, NTD and DS
      are influenced by the same genetic determinants of one-carbon metabolism. The
      distinct data produced in different geographical areas may be explained by
      differences in the nutritional environment and genetic characteristics of the
      populations.

PMID- 14656029
TI  - Functional vitamin B12 deficiency and determination of holotranscobalamin in
      populations at risk.
AB  - BACKGROUND: The prevalence of a sub-clinical functional vitamin B12 deficiency in
      the general population is higher than previously expected. Total serum vitamin
      B12 may not reliably indicate vitamin B12 status. To get more specificity and
      sensitivity in diagnosing vitamin B12 deficiency, the concept of measuring
      holotranscobalamin II (holoTC), a sub-fraction of vitamin B12, has aroused great
      interest. HoloTC as a biologically active vitamin B12 fraction promotes a
      specific uptake of its vitamin B12 by all cells. In this study we investigated
      the diagnostic value of storage (holoTC) of vitamin B12 and functional markers
      (methylmalonic acid (MMA)) of vitamin B12 metabolism in populations who are at
      risk of vitamin B12 deficiency. SUBJECTS AND METHODS: Our study included 93
      omnivorous German controls, 111 German and Dutch vegetarian subjects, 122 Syrian
      apparently healthy subjects, 127 elderly Germans and finally 92 German pre
      dialysis renal patients. Serum concentrations of homocysteine (Hcy) and MMA were
      measured by gas chromatography-mass spectrometry, folate and vitamin B12 by
      chemiluminescence immunoassay, and holoTC by utilizing a RIA test. RESULTS: High
      Hcy (>12 micromol/l), high MMA (>271 nmol/l) resp. low holoTC (vitamin B12) in
      serum were detected in 15%, 8% resp. 13% (1%) of German controls, 36%, 60%, resp.
      72% (30%) of vegetarians, 42%, 48% resp. 50% (6%) of Syrians, 75%, 42%, resp. 21%
      (7%) of elderly subjects and 75%, 67% resp. 4% (2%) of renal patients. The lowest
      median levels of holoTC were observed in vegetarians, followed by the Syrian
      subjects (23 and 35 pmol/l, respectively). Renal patients had significantly
      higher levels of holoTC compared to the German controls (74 vs. 54 pmol/l). In
      the vitamin B12 range between 156 pmol/l (conventional cut-off level) and 241
      pmol/l, both mean concentrations of holoTC and MMA were in the pathological
      range. HoloTC was the earliest marker for vitamin B12 deficiency followed by MMA.
      Vitamin B12 deficiency causes folate trapping. A higher folate level is required
      to keep Hcy normal. The relationship between MMA and holoTC seemed dependent on
      renal function. In renal patients with a glomerular filtration rate below 36
      ml/min, a significantly lower mean level of MMA was detected within the highest
      tertile of holoTC concentration, compared to the lowest tertile. Thus, in renal
      patients, a higher serum concentration of circulating holoTC is required to
      deliver sufficient amounts of holoTC into the cells. CONCLUSION: Our data support
      the concept that the measurement of holoTC and MMA provides a better index of
      cobalamin status than the measurement of total vitamin B12. HoloTC is the most
      sensitive marker, followed by MMA. The use of holoTC and MMA enables us to
      differentiate between storage depletion and functional vitamin B12 deficiency.
      Renal patients have a higher requirement of circulating holoTC. In renal
      dysfunction, holoTC cannot be used as a marker of vitamin B12 status.

PMID- 14656030
TI  - Holotranscobalamin as a predictor of vitamin B12 status.
AB  - We report on the performance of a new test, holotranscobalamin, as compared to
      well established markers of vitamin B12 deficiency (plasma cobalamins,
      methylmalonic acid, and homocysteine). Holotranscobalamin was analyzed in 143
      samples by a competitive radiobinding assay (Axis-Shield). Employing a cut-off
      value of 50 pmol/l, holotranscobalamin showed a sensitivity of 1.00 and a
      specificity of 0.89 as regards discriminating between individuals with test
      results indicating vitamin B12 deficiency (methylmalonic acid > 0.70 micromol/l
      and plasma cobalamins < 200 pmol/l, n = 35) and individuals with test results
      inside the reference intervals (methylmalonic acid < 0.29 micromol/l and plasma
      cobalamins > or = 200 pmol/l, n = 35). In a group (n = 37) with low plasma
      cobalamins (< 200 pmol/l) and normal methylmalonic acid (< 0.29 micromol/l), 27
      individuals had low holotranscobalamin, and in nine of these individuals plasma
      homocysteine supported the deficiency state (homocysteine > 15 micromol/l).
      Holotranscobalamin was low in 12 individuals with increased methylmalonic acid (>
      0.40 micromol/l) and normal plasma cobalamins (> or = 200 pmol/l) (n = 36), and
      plasma homocysteine supported the deficiency state in four of these individuals.
      We conclude that holotranscobalamin is likely to be a sensitive marker of vitamin
      B12 deficiency that also has a reasonable specificity. Large-scale clinical
      studies are warranted in order to clarify the usefulness of holotranscobalamin in
      the clinical setting.

PMID- 14656031
TI  - Hyperhomocysteinemia and B-vitamin status after discontinuation of oral
      anticoagulation therapy in patients with a history of venous thromboembolism.
AB  - Although hyperhomocysteinemia is an established risk factor for venous
      thromboembolism there is no consensus for routine determination of circulating
      homocysteine in the UK, either at the beginning or end of oral anticoagulation
      therapy. The purpose of this study was to evaluate the prevalence of
      hyperhomocysteinemia and its relationship to folate and vitamin B12 status in
      subjects with venous thromboembolism 4 weeks after discontinuation of warfarin
      therapy. In 78 consecutively recruited patients, plasma homocysteine was
      significantly higher (p < 0.001) and red cell folate significantly lower (p =
      0.03) than in controls. Plasma vitamin B12 was similar in both groups.
      Strikingly, 38.5% of patients had hyperhomocysteinemia (> 15 micromol/l).
      Retrospective analysis revealed a significant positive association between plasma
      total homocysteine and duration of warfarin therapy (p < 0.001) but a negative,
      though non-significant (p = 0.06), trend with warfarin dose. The results do not
      suggest any direct interaction between warfarin and plasma homocysteine but raise
      the possibility of reduced intake of a common food source of folate and vitamin
      K. One possibility is the shortage of green-leafy vegetables since patients are
      often advised to limit their intake of this major source of vitamin K. On the
      basis of this study we suggest that homocysteine screening should be carried out
      at the time that patients begin warfarin therapy.

PMID- 14656032
TI  - Measurement of carotid plaque and effect of vitamin therapy for total
      homocysteine.
AB  - BACKGROUND: Many new therapies are being developed that are anti-atherosclerotic,
      but which do not change clinical parameters such as blood pressure or
      cholesterol. In order to measure the effects of these therapies it will be
      necessary to measure atherosclerosis. Elevated levels of plasma total
      homocysteine (tHcy) are associated with increased risk of stroke and myocardial
      infarction. Measurement of the effect of vitamin therapy on atherosclerosis has
      therefore been used as an example of this approach. METHODS: 2-Dimensional
      measurement of carotid plaque cross-sectional area has been used to measure
      effects of vitamin therapy in patients whose plaque is progressing despite
      intensive treatment of traditional risk factors. In clinic patients, addition of
      vitamin therapy halted progression of atherosclerosis, in samples of 50 patients
      over 2.5 years. However, in patients randomized to high-dose vs. low-dose
      vitamins in the Vitamin Intervention for Stroke Prevention trial, no difference
      in plaque progression was seen between high-dose and low-dose vitamin therapy.
      New methods have been developed for the measurement of 3-dimensional plaque
      volume, and for the measurement of plaque surface roughness. RESULTS: The
      accuracy and reliability of the measurement of plaque volume is 95%. This will
      permit measurement of effects of new anti-atherosclerotic therapies with much
      smaller sample sizes, in a much shorter time, than previously available methods
      such as intima-media thickness. CONCLUSION: Measurement of atherosclerotic plaque
      volume and roughness will greatly enhance the study of new anti-atherosclerotic
      therapies.

PMID- 14656033
TI  - Folate improves endothelial function in patients with coronary heart disease.
AB  - Elevated plasma homocysteine is associated with increased cardiovascular risk but
      it remains unproven that the effect is directly causal. Folate and homocysteine
      metabolism are closely linked such that administration of folic acid in doses
      ranging from 0.2-10 mg/day lowers plasma total homocysteine (tHcy) by up to 25%.
      Folic acid has been widely advocated as a therapy which may reduce cardiovascular
      risk, but the clinical benefit remains as yet unproven and the choice of dose
      remains unclear. The effect of folic acid on endothelial function has been
      investigated in patients with proven coronary heart disease (CHD) by measuring
      flow-mediated dilatation (FMD) in the brachial artery. Oral folic acid (5 mg/day)
      markedly enhances endothelial function (FMD) and lowers homocysteine. Studies of
      the acute effects of folic acid have shown that this improvement occurs within
      the first 2-4 hours following the first dose, at which times there was no
      significant reduction in plasma tHcy. Administration of 5-methyltetrahydrofolate
      directly into the brachial artery markedly enhances FMD, an effect that is
      blocked by monomethyl arginine (LNMMA), suggesting that the effects of folate are
      mediated by nitric oxide. This Review summarises studies which show that
      pharmacological doses of folate markedly enhance endothelial function in patients
      with CHD. The discordance with changes in plasma homocysteine suggests that these
      effects may occur by mechanisms distinct from homocysteine lowering.

PMID- 14656034
TI  - The impact of hyperhomocysteinemia as a cardiovascular risk factor in the
      prediction of coronary heart disease.
AB  - Coronary heart disease often occurs in the absence of traditional risk factors.
      Consequently, epidemiological studies exploring novel risk factors are necessary
      to improve the prediction of coronary heart disease. This study evaluated five
      promising markers of cardiovascular risk: homocysteine, C-reactive protein,
      fibrinogen, lipoprotein(a) (Lp(a)), free apolipoprotein(a) (apo(a)) and Lp(a)
      phenotypes. The study included 135 patients with angiographically confirmed
      atherosclerosis. The control group consisted of 93 sex- and age-matched
      individuals. The Mann-Whitney U-test was used for group comparison. New risk
      factors were evaluated by binary logistic regression. The odds ratios were
      calculated continuously for homocysteine in dependence on C-reactive protein. Low
      density lipoprotein (LDL)-cholesterol was nearly identical in controls and
      patients. Homocysteine, C-reactive protein, fibrinogen, high density lipoprotein
      (HDL)-cholesterol and Lp(a) discriminated highly significantly between both
      groups. The continuously calculated odds ratio for homocysteine demonstrated a
      distinct influence of C-reactive protein. In the group with high C-reactive
      protein levels, homocysteine levels above 9.6 micromol/l resulted in a markedly
      elevated risk (odds ratio 12), in the group with C-reactive protein levels below
      5 mg/dl, a comparable risk increase was observed at a homocysteine level of 16.6
      micromol/l. This data strongly suggests that plasma homocysteine helps identify
      individuals at risk, especially among those with elevated C-reactive protein
      levels.

PMID- 14656035
TI  - Homocysteine increases during endurance exercise.
AB  - Hyperhomocysteinemia is a risk factor for cardiovascular and other diseases.
      Recently many endogenous and exogenous modulators of homocysteine (Hcy) have
      become known, e.g., B-vitamins. However, little is known about the effect of
      exercise on Hcy. The purpose of this study was to investigate the effect of three
      different types of acute endurance exercise on serum Hcy. We measured Hcy in 100
      recreational athletes (87 males, 13 females) who participated in a marathon race
      (n = 46), a 100 km run (100 km; n = 12) or a 120 km mountain bike race (n = 42).
      Blood samples were taken before, 15 min and 3 h after the race. In athletes with
      pre-race Hcy > 12 micromol/l we also determined folate and vitamin B12. Marathon
      running induced a Hcy increase of 64%, while mountain biking and 100 km running
      had no significant effect on Hcy. Pre-race Hcy (25th-75th percentile) overall;
      marathon race; 100 km; mountain bike race was 9.7 (7.1-11.5) micromol/l; 9.8 (7.4
      11.1) micromol/l; 10.2 (6.6-13.2) micromol/l; 9.1 (6.9-13.5) micromol/l,
      respectively. At 15 min and 3 h post-race, Hcy was 11.9 (8.4-16.4) micromol/l;
      16.1 (12.7-20.4) micromol/l; 9.5 (7.8-15.9) micromol/l; 8.8 (7.1-11.2)
      micromol/l, respectively, and 11.5 (8.9-15.7) micromol/l; 14.9 (11.5-20.0)
      micromol/l; 10.0 (8.1-11.8) micromol/l; 9.4 (7.4-12.1) micromol/l, respectively.
      The change in Hcy correlated negatively with the running time. Twenty-three
      athletes had pre-race Hcy levels > 12 micromol/l, which were associated with
      relatively low folate (14.3 (11.6-18.9) nmol/l) and vitamin B12 levels (231 (183
      261) pmol/l). Endurance exercise may induce a considerable Hcy increase, which
      varies between different disciplines and is most probably determined by the
      duration and intensity of exercise. Furthermore, about 25% of recreational
      endurance athletes exhibited hyperhomocysteinemia in association with low vitamin
      B12 and folate levels.

PMID- 14656036
TI  - Comparison of the influence of volume-oriented training and high-intensity
      interval training on serum homocysteine and its cofactors in young, healthy
      swimmers.
AB  - BACKGROUND: Since homocysteine (Hcy) is a risk factor for cardiovascular and
      other diseases, it is important to know how exercise can modify it. Previous
      studies have suggested that endurance training influences Hcy. However, little is
      known about the effect of training intensity on Hcy. MATERIALS AND METHODS: We
      investigated Hcy, vitamin B12, vitamin B6, folate and methylmalonic acid (MMA)
      before and after 3 weeks of volume-oriented training (VOL) (30 km/week) and high
      intensity interval training (HIT) (20 km/week) in 20 young swimmers (16 +/- 2
      years). Afterward, the athletes completed 5 days of recovery training. RESULTS:
      The training induced a Hcy increase in HIT and VOL (6.47 +/- 0.95 micromol/l vs.
      7.44 +/- 1.17 micromol/l and 7.33 +/- 1.92 micromol/l vs. 8.28 +/- 1.42
      micromol/l, respectively) that persisted during the recovery period (8.02 +/-
      1.69 micromol/l and 8.00 +/- 1.81 micromol/l, respectively). Vitamin B12 was
      unchanged after the training (539 +/- 166 ng/l vs. 556 +/- 192 ng/l and 480 +/-
      144 ng/l vs. 491 +/- 124 ng/l, respectively) but decreased during the recovery
      period (459 +/- 134 ng/l and 451 +/- 116 ng/l, respectively). Folate showed an
      increase during the training (9.07 +/- 2.01 microg/l vs. 11.71 +/- 4.08 microg/l
      and 10.34 +/- 2.32 microg/l vs. 11.13 +/- 4.64 microg/l, respectively), which was
      reversible by the end of the recovery training (8.57 +/- 1.98 microg/l and 9.60
      +/- 2.38 microg/l, respectively). Vitamin B6 and MMA did not change. For none of
      the measured parameters were there significant differences between HIT and VOL.
      CONCLUSION: Three weeks of strenuous swimming caused a prolonged Hcy increase,
      which was accompanied by changes in vitamin B12 and folate. The magnitude of
      these effects was not influenced by the training intensity.

PMID- 14656037
TI  - Analysis of the transcobalamin II 776C>G (259P>R) single nucleotide polymorphism
      by denaturing HPLC in healthy elderly: associations with cobalamin, homocysteine
      and holo-transcobalamin II.
AB  - A relatively new method for the detection of single nucleotide polymorphisms is
      the use of denaturing high-performance liquid chromatography (DHPLC). DHPLC was
      used to analyse the transcobalamin II 776C>G polymorphism in DNA from 159 healthy
      elderly. Furthermore, cobalamin, folate, homocysteine and holo-transcobalamin II
      (holo-TC II) were measured. The allele frequency of the G-allele was 17% with n =
      55 harbouring the CC genotype, n = 77 being heterozygous and n = 27 showing the
      GG genotype. Holo-TC II concentrations were significantly decreased in patients
      harbouring the GG genotype. There was no effect on cobalamin, methylmalonyl-CoA,
      folate or homocysteine concentrations. A new G>A variant at nucleotide position
      810 in the TC II gene was detected by an altered peak pattern in the DHPLC and
      further elucidated by direct sequencing. The TC II G810A variant is a silent
      mutation without replacement of the corresponding amino acid (alanine) at
      position 270 in the TC II protein and was only found as a heterozygous genotype
      in a single patient. The new variant would have been undetected by other methods
      used for single nucleotide polymorphism detection, e.g., restriction fragment
      length polymorphism analysis. The results suggest that the common TC II 776C>G
      polymorphism has no major influence on vitamin B12 metabolism.

PMID- 14656038
TI  - Introductory remarks: why do we need to look for a more humanized medicine?

PMID- 14656039
TI  - Vulnerability and salutogenesis in health and disease.
AB  - In this brief overview psychosocial factors which contribute to health and
      disease are briefly discussed. These opposing factors are mainly investigated in
      a unidirectional sense and often neutralize each other and thereby explain only
      little variance. The normally investigated pathological factors would have to be
      supplemented by salutogenic (health promoting) factors and vice versa. The
      salutogenic perspective opens up a resource-oriented approach, which can reduce
      suffering and also health care costs in almost any kind of disease. There is
      enough empirical evidence, of which only a small part is presented here, to
      support this claim.

PMID- 14656040
TI  - Family medicine as a frame for humanized medicine in education and clinical
      practice.

PMID- 14656041
TI  - Language and the physician.

PMID- 14656042
TI  - Pandemic obesity and the contagion of nutritional nonsense.
AB  - The United States is the epicenter of an obesity pandemic. As more countries
      acculturate to a Western lifestyle, rates of obesity and its sequelae are rising
      steadily in both adults and children. In response, a variety of weight-loss diets
      emphasizing alternative distributions of macronutrient classes have been promoted
      with considerable success. Among the most popular is the so-called "Atkins Diet,"
      in which carbohydrate restriction is touted as the key to weight loss. Despite
      claims, however, evidence that weight loss is enhanced by means other than
      caloric restriction is lacking. Also lacking is evidence that fad diets produce
      sustainable weight loss. Most important, fad diets generally ignore or refute
      what is known about fundamental associations between dietary pattern and human
      health. Cancer, cholera, and AIDS induce rapid weight loss, highlighting the
      potential incompatibility of weight loss by any means with health. Available data
      suggest that long-term weight loss is most consistently achieved by adherence to
      a fat-restricted diet abundant in grains, vegetables, and fruit, along with
      regular physical activity, a lifestyle notably conducive to the promotion of
      overall health. Fad diets, potential harms of which are well characterized,
      should be presumed "guilty" of incompatibility with human health until or unless
      proved otherwise; the burden of proof should reside with proponents. In the
      interim, the clinical and public health communities should work to empower
      individuals with knowledge needed to reconcile weight control with health
      promotion; support policies that mitigate obesogenic environmental conditions;
      and offer unified resistance to the contagion of dietary propaganda.

PMID- 14656043
TI  - Medical services for persons with intellectual disability in Israel.
AB  - BACKGROUND: The first school for children with intellectual disability (ID) was
      opened in Tel Aviv in 1929; the first boarding school for children with ID was
      established in Jerusalem in 1931; and the first center for assessment of children
      with ID established in Tel Aviv in 1936. With the establishment of the State of
      Israel in 1948, there was a total of four residential care centers providing
      services for 150 children with ID. OBJECTIVE: This paper will describe the
      history and development of the public health work with persons with intellectual
      disability from the birth of the State of Israel in 1948 until today, with a
      focus on medical and nursing care and ideas for future work with this population.
      DATA SOURCES: Studies and documents from the Office of the Medical Director,
      Division for Mental Retardation of the Ministry of Social Affairs in Israel. DATA
      EXTRACTION: The Division for Mental Retardation is in contact with approximately
      23,000 persons of all ages. Residential care is provided to about 6,000 persons
      in 54 institutions countrywide. In addition, 2,000 persons receive residential
      care in hostels or protected apartments within the community. More than 50 other
      settings provide vocational and educational services to 15,000 persons--day-care
      kindergartens, day-treatment centers, sheltered workshops, or integrated care
      within the community. DATA SYNTHESIS: Data on the health profile, morbidity, and
      mortality of the residents in residential care centers are used to illustrate the
      medical and nursing work with this population. CONCLUSIONS: We recommend that the
      direction in Israel should be a combination of both community and institutional
      care for the population of persons with ID. We recommend the establishment of a
      subspecialty for physicians and nurses in intellectual disability and the
      establishment of a Health Division within the Ministry of Social Affairs to
      facilitate better service, education, and research.

PMID- 14656044
TI  - Compliance with influenza and pneumococcal vaccinations in Israel, 1999-2002.
AB  - BACKGROUND: In a previous study, we found a relatively low compliance with
      influenza vaccination among the elderly (65 years and over) in both 1998/1999 and
      1999/2000 winters. Prior to the 2000/2001 winter season, a campaign was conducted
      by the Israeli Ministry of Health and the local health maintanance organizations
      for improving compliance with influenza and pneumococcal vaccinations. The main
      purpose of the present study was to monitor the impact of that campaign on
      compliance with influenza and pneumococcal vaccinations. OBJECTIVES: (a) To
      compare the compliance rate of target groups with influenza vaccination in Israel
      during 2000/2001 and 2001/2002 winter seasons with previous years, (b) to
      estimate the compliance rate of the elderly with pneumococcal vaccination in
      Israel in the last 5 years, (c) to determine reasons for non-compliance. METHODS:
      Questions about compliance with influenza and pneumococcal vaccinations were
      included in quarterly national telephone surveys monitoring acute morbidity in
      Israel. Each survey was based on a sample of about 900 households and was carried
      out during three successive evenings. Questions were directed at interviewees of
      18 years and over who were asked to report the vaccnation status of all the
      household members. RESULTS: A gradual increase in compliance with influenza
      vaccination was demonstrated for the elderly (aged 65 years and over) in the
      2000/2001 (54.4%) and 2001/2002 (60.8%) winter seasons compared to the previous
      two seasons (51.6% in 1998/1999 and 49.1% in 1999/2000). A slight nonsignificant
      increase was also observed in the 50-64 age group (18.3% in 2002 survey). The
      proportion of the elderly who were reported to be vaccinated against pneumonia in
      the five years preceding the interview was higher in the 2002 survey (27.9%)
      compared to that of 2001 (20.1%). Lack of physician recommendation and low
      degreee of risk perception seem to be the major reasons hindering the achievement
      of higher rates of vaccination coverage. CONCLUSION: The vaccination campaign
      carried out in Israel prior to the 2000/2001 winter season was moderately
      successful in increasing the coverage of influenza and pneumococcal vaccinations
      in target groups. Performing this type of campaign every year before the
      influenza season should contribute to improving the compliance with vaccination
      of target groups.

PMID- 14656045
TI  - Pathogenic role of matrix metalloproteases and their inhibitors in asthma and
      chronic obstructive pulmonary disease and therapeutic relevance of matrix
      metalloproteases inhibitors.
AB  - Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and
      zinc dependent enzymes implicated in many physiological and pathological
      processes. Asthma, chronic obstructive pulmonary disease (COPD) and emphysema are
      diseases associated with an inflammation of the airways and lung parenchyma. In
      this review, we focus on the role played by MMPs in the pathogenesis of
      inflammation, airway remodelling and alveolar destruction, depicting the
      observational studies in humans and the experimental studies in animal models.
      During the course of asthma, MMP-2,-8,-9 and TIMP-1 are expressed at baseline and
      the allergen exposure or exacerbations of the disease lead to an increase of MMP
      9 secretion being at this time much higher than that of TIMP-1, allowing
      temporarily a matrix damage, possibly followed by abnormal repair. Animal models
      suggest a predominant role for MMP-9 and MMP-12 in the pathogenesis of pulmonary
      inflammation and link an absence of MMP-2 to an increased parenchymal
      inflammation. In COPD and emphysema, human studies indicate an over-secretion of
      MMP-2,-8,-9 and animal models pointout MMP-1 and MMP-12 as being key players in
      the pathogenesis of emphysema. Taken together, these data identify specific MMP
      inhibition as appropriate target for therapeutic intervention in asthma or
      COPD/emphysema They also strongly argue against the widespread use of large
      spectrum non specific inhibitors that could be detrimental.

PMID- 14656046
TI  - Nitric oxide synthase, an essential factor in peripheral nerve regeneration.
AB  - Nitric oxide (NO) exerts both, pro-apoptotic and anti-apoptotic actions and
      appears to be acritical factor inneuronal degenerative and regenerative
      processes. NO is synthesized from L-arginine by NO synthase occurring in three
      isoforms of (neuronal, nNOS; endothelial, eNOS; inducible, iNOS). In a mice
      sciatic nerve model the regenerative outcome was assessed when the endogenous NO
      supply was deficient by knocking out the respective NOS isoform and compared to
      that of wild type mice after nerve transection. In nNOS knock-out mice a delay in
      regeneration, preceded by slowedWallerian degeneration and a disturbed pruning of
      uncontrolled sprouts, was observed. This was associated with a delayed recovery
      of sensory and motor function. Additionally, deficiency of nNOS led after nerve
      cut to a substantial loss of small and medium-sized dorsal root ganglia neurons,
      spinal cord interneurons and, to a lesser extent, spinal cord motor neurons. A
      lack of iNOS resulted in a delayed Wallerian degeneration and impaired
      regenerative outcome without consequences for neuronal survival. A lack of eNOS
      was well tolerated, although a delay in nerve revascularization was observed.
      Thus, after peripheral nerve lesion, regular NOS activity is essential for cell
      survival and recovery with reference to the nNOS isoform.

PMID- 14656047
TI  - Morphology, homogeneity and functionality of human monocytes-derived macrophages.
AB  - Primary cultures of human monocyte-derived macrophages (n = 50) were
      characterized in order to use this cellular model to establish a proteomic map of
      macrophages. Peripheral blood mononuclear cells were isolated from healthy
      donors' blood using density gradient centrifugation. The cell culture quality was
      checked in respect of several morphological and molecular aspects. The
      homogeneity and purity of cells was assessed after 12 days' primary culture with
      phase microscopy, immunocytochemistry and flow cytometry. Monocytes were
      completely differentiated into macrophages within 12 days as shown by phase
      microscopy. On day 12, all cells expressed CD68 antigen and were negative for
      CD3. Flow cytometry experiments showed a purity of the primary culture on day 12,
      in a range between 76% and 98% of CD14+ cells. The functionality of cells was
      characterized for the presence of ECE-1 as an intracellular marker and for the
      presence of MMP-9 as a marker secreted into the culture medium. This study
      allowed to determine criteria of quality and functionality for the primary
      culture of monocyte-derived macrophages. Cultures meeting these criteria will be
      used for the proteomic analysis and the establishment of the reference map.

PMID- 14656048
TI  - Oncogenic receptor tyrosine kinase in leukemia.
AB  - Growth, survival and differentiation of hematopoietic cells are regulated by the
      interaction between hematopoietic growth factors and their receptors. While the
      defect in this interaction results in an insufficient hematopoiesis, the
      aberrantly elevated activation leads to the transformation of hematopoietic
      cells. The constitutive active mutations of receptor tyrosine kinase, such as c
      Kit platelet-derived growth factor receptor (PDGFR) or fins-like tyrosine kinase
      3 (Flt3), play a major role in the development of hematopoietic neoplasia. The
      constitutive activation is provoked by several mechanisms, such as making fusion
      genes by chromosomal translocations, or various mutations involving regulatory
      regions of the receptor. The chromosomal translocation brings the receptor
      intracytoplasmic domain juxtaposed to an unrelated molecule which has
      dimerization or multimerization motif, resulting in the constitutive dimerization
      of the receptor. The missense, insertion or deletion mutations in the regulatory
      regions, such as juxtamembrane domain, activation loop and extracellular domain,
      cause constitutive activation by releasing the respective auto-inhibitory
      functions of each regulatory region. Constitutive active receptors generate
      different signals quantitatively and qualitatively from wild type receptor, which
      mediate the oncogenic phenotype. Given the frequent involvement of constitutive
      active receptor tyrosine kinase in hematopoietic malignancies, targeted
      inhibitions of active tyrosine kinase and downstream aberrant signaling are
      rapidly developing novel therapeutic modality with much promise.

PMID- 14656049
TI  - Insulin increases the intracellular concentration of total oxalyl thiolesters in
      BC3H-1 myocytes: potential anti-insulin mediators.
AB  - Oxalyl thiolesters (RS-CO-COOH) may represent negative intracellular messengers
      for insulin action. Using a reverse-phase, ion-pair high pressure liquid
      chromatographic technique, total intracellular oxalyl thiolesters were measured
      in insulin-sensitive BC3H-1 myocytes after the addition of insulin. The total
      oxalyl thiolester concentration increased to a maximum of 2.9 times the basal
      concentration by 30 min after the addition of 100 microU/ml insulin and decreased
      to 1.8 times by 180 min. Insulin's stimulation of pyruvate dehydrogenase as
      measured by lactate oxidation ([1-14C]-lactate --> 14CO2) in intact BC3H-1
      myocytes reached a maximum at 15-30 min and returned to basal activity during the
      60-90 min measurement interval. These results suggest that oxalyl thiolesters are
      increased in concentration following insulin-induced signal transduction to
      reverse insulin-stimulated metabolic events.

PMID- 14656051
TI  - Two selective rat adrenomedullin (AM)-receptor antagonists: AM20-50 and AM24-50.
AB  - Adrenomedullin (AM) is a hypotensive peptide, which is produced in several organs
      and tissues, the functions of which it regulates in a autocrine-paracrine manner.
      Rat (r) and human (h) AM are 50- and 52-amino acid peptides, which differ for 2
      amino acid deletions and six substitutions and contain a disulfide bridge-formed
      six-membered ring between adjacent cysteine residues in the 14 and 19 and 16 and
      21 positions, respectively. The amidated C-terminal sequence is needed for AM to
      bind its receptors, and the ring structure (but not t he N-terminal sequence)
      seems to be required for AM to activate its receptors. Hence, we examined the
      effectiveness of some N-terminus and ring-lackingAM fragments as AM-receptor
      antagonists in the rat zona glomerulosa (ZG), whose cells are provided with
      abundant AM binding sites and display an AM-induced inhibition of K+-stimulated
      aldosterone secretion. Quantitative autoradiographic studies showed that cold
      rAMI-50, rAM20-50 and rAM24-50 displaced [125I]AM1-50 binding from rat ZG with
      the same potency and efficacy, which were significantly higher than those of hAM1
      52, hAM22-52 and hAM26-52. Accordingly, rAM20-50 and rAM24-50 reversed the
      inhibitory effect of 10(-8) M rAMI-50 on aldosterone response of dispersed rat ZG
      cells to 10(-2) M K+ with significantly higher potency and efficacy than hAM22-52
      and hAM26-52. Taken together, our findings confirm that CONH2-terminal AM
      fragments, lacking the six-membered ring structure, act as antagonists of AM
      receptors in the rat ZG. Moreover, they provide the first evidence that rAMI-50
      and its fragments should be used in the investigations carried out in the rat.

PMID- 14656050
TI  - Structural and electronic properties of tyrosine kinases inhibitors.
AB  - Protein tyrosine kinases (TKs) regulate cell proliferation, cell differentiation,
      and play a fundamental role in signal transduction pathway. Uncontrolled
      signaling from receptor tyrosine kinases and intracellular tyrosine kinases was
      related to diseases such as cancer, atherosclerosis and psoriasis. For the
      present study, we selected a number of structurally related ATP-binding site
      inhibitors of EGF-receptors of diverse classes. Molecular properties of
      competitive inhibitors are key features for the action mechanism of these
      compounds. We performed a theoretical study at the RHF/6-311G* level of theory,
      in order to correlate the molecular parameters with the biological inhibitory
      activities. Species stability as evaluated by ionization potentials as well as
      the E(HOMO)-E(LUMO) energy gap, is in very good correlation with higher
      inhibitory potency (IP). The most active species, 1, 5, 6,10,11 and 12 exhibited
      strongly negative charged atoms over the C6 and C7 positions, the higher IP,
      higher mu and higher energy gap. In summary, a good correlation was observed
      between the molecular parameters, such as ionization potential, dipolar moment
      and E(HOMO)-E(LUMO) energy gap and inhibitory potency, suggesting that these
      properties play an important role for the interaction at the ATP-binding site of
      EGF-receptors.

PMID- 14656052
TI  - Chronic administration of losartan reverses cardiovascular changes in
      hypertensive fructose-fed rats.
AB  - The cluster of risk factors including hyperinsulinemia, insulin resistance,
      hypertriglyceridemia and hypertension has been called syndrome X. Several
      evidences link the insulin resistance syndrome with endothelial dysfunction.
      Since the participation of the renin-angiotensin system (RAS) in this pathology
      is still unclear, the present study examined the effect of chronic administration
      of an angiotensin AT1 receptor antagonist, losartan (L), on endothelial nitric
      oxide synthase (eNOS) activity in aortic endothelium and cardiac tissue, and on
      the proliferation of primary cultured aortic smooth muscle cells (SMC), obtained
      from fructose-fed rats (FFR), an experimental model of syndrome X Male Wistar
      rats were used: Control, FFR and FFR+L (n = 8 in each group). After 8 weeks,
      tissue samples were obtained and 10% fetal calf serum (FCS) proliferative effect
      was examined in SMC by 3H-thymidine incorporation and cell counting. The eNOS
      activity was estimated in aortic endothelial lining and cardiac homogenates by
      conversion of 3H-arginine into 3H-citrulline. FFR aortic SMC showed a
      significantly increased 10% FCS-induced 3H-thymidine incorporation and cell
      number compared to controls. FFR aortic and cardiac eNOS activities were
      significantly decreased. Chronic treatment with L decreased systolic blood
      pressure,reverted cardiac hypertrophy, abolished the increased SMC proliferation
      and restoredeNOS activity. These data confirm that changes in SMC proliferation
      and endothelial dysfunction at different levels of the cardiovascular system are
      involved in syndrome "X", and that AT1 receptor blocking can revert those
      changes, suggesting an important role of the RAS, possibly mediated by AT2
      receptors and kinins, in the physiopathological mechanisms of this model.

PMID- 14656053
TI  - Prolonged ethanol ingestion decreases alpha-mannosidase activity and induces its
      redistribution to the fluid phase in rat cauda epididymis.
AB  - The role of glycosidases in mammalian epididymal fluid is still a controvertial
      subject. There exists a body of evidence in favour of a function in remodeling
      the sperm surface as one step in gamete maturation, whilst others argue in favor
      of an extraepididymal role for these enzymes. In this study we measured the
      activity and distribution of four glycosidases in rat cauda epididymis after
      prolonged ethanol ingestion, a condition associated with fertility disturbances.
      We found that alpha-mannosidase is the most sensitive enzyme to the stress caused
      by alcohol, since its activity in epididymis significantly decreased and partly
      redistributed from the spermatozoa to the fluid phase. From these results we
      suggested that alcohol treatment affects the expression of the enzyme and
      possibly induces a loss of interaction with the affinity sites on the sperm
      surface. Although other enzymes also underwent changes due to the alcohol
      treatment, we focussed on the importance of alpha-mannosidase in the fertilizing
      capability of spermatozoa.

PMID- 14656054
TI  - Sucrose increases calcium-dependent protein kinase and phosphatase activities in
      potato plants.
AB  - The effect of sucrose on tuber formation, calcium-dependent protein kinase (CDPK)
      and phosphatase activities was analysed using in vitro cultured potato plants. In
      short treatments, sucrose induced CDPK and phosphatase activities. In long
      treatments, sucrose induced tuber formation in the absence of other tuber
      inducing stimuli. Sorbitol caused a minor increase in CDPK activity and affected
      plant morphology but did not induce tuber development. The addition of the
      protein kinase inhibitor Staurosporine precluded sucrose-induced tuberization.
      Altogether, our results suggest that phosphorylation/dephosphorylation events are
      involved in sucrose-induced tuber development.

PMID- 14656055
TI  - A neuroimmune regulation at peripheral level on the steroidogenesis of polycystic
      ovary in rats.
AB  - It is known that noradrenergic sympathetic nerve fibers connect the ovary and the
      spleen from the celiac ganglion. The modulation of the ovarian steroidogenesis in
      rats with polycystic ovary (PCO) by secretions of culture splenocytes from
      control (non PCO), PCO and PCO rats with superior ovarian nerve transection
      (PCO+SON-t) is investigated. Splenocytes from PCO rats increased progesterone (P)
      and decreasing estradiol (E) and androstenedione (A) release, a steroidogenic
      response different from that obtained with splenocytes of control rats. PCO also
      decreased the number of splenocyte beta-adrenergic receptors (betaR). SON
      transection reverted the effect of PCO on splenocytes betaR numbers and
      secretions of these splenocytes also reverted the stimulatory effect of PCO on P
      release, while norepinephrine (NE) treatment to PCO+SON-t splenocytes decreased
      their betaR number and their secretions restored the stimulation on progesterone
      release. Inversely, PCO+SON-t splenocyte secretions intensified the inhibition in
      estradiol with no effect on A. Treatment of PCO+SON-t splenocytes with NE or
      neuropeptide Y partially reverted the effects of PCO and SON-t The P and E-A
      response of PCO ovary might be differentially regulated by the splenocyte
      secretions through the neural connection involving ovary, SON, celiac ganglion
      and spleen and the neurotransmitter NE.

PMID- 14656056
TI  - A new addition to the structural bioinformatics toolbox: 3D models of short
      bioactive peptides from multiple sequences using feedback restrained molecular
      dynamics (FRMD).
AB  - Modem molecular biology techniques allow the use of new approaches for the 3D
      mapping of 1D information. Molecular biology techniques are capable of producing
      large amounts of 1D information (sequences) from a number of different sources
      (phage displays, ESTs, etc.). In this work, we present a technique that takes
      advantage of large sets of 1D information and increasingly available computer
      power to create 3D models. For the purpose of validation the technique is first
      applied to the modeling of an erythropoietin analog of known 3D structure from 1D
      information only. The technique is then used to model the immunoreactive region
      of echinococcus granulosus AgB based on phage raised mimotopes for which there is
      no previous structural information. The technique here presented is of general
      application to similar problems where 1D information is available and structure
      activity relationships (SAR) is needed.

PMID- 14656057
TI  - Conformational changes induced by cloxacillin in class a beta-lactamase from
      Bacillus cereus.
AB  - Class A beta-lactamases are enzymes that hydrolyse beta-lactam antibiotics such
      as penicillins and cephalosporins. They also hydrolyse substrate analogues such
      as oxacillin and cloxacillin, with a biphasic kinetic as it has been reported for
      Bacillus cereus beta-lactamase. A molecular model of Bacillus cereus beta
      lactamase was built and the conformational changes that the substrates
      benzylpenicillin and cloxacilline produced in the conformation of selected
      regions of the protein were analyzed. This study was performed using the docking
      of the substrates, their tetrahedral intermediates and the corresponding acids on
      the active site, followed by molecular dynamic and subsequent optimisation
      procedures. The most important changes were produced on Tyr105 and Tyr273, when
      the tetrahedral intermediate of cloxacillin was docked at the active site, these
      amino acids are partially responsible for the stabilisation of the substrates at
      the active site. These changes may explain the kinetic differences observed
      during the hydrolysis of substrates type S and type A by beta-lactamases class A.

PMID- 14656058
TI  - Binding of vinyl polymers to anionic model membranes.
AB  - The association of poly2-vinylpyridine (P2VPy) and poly4-vinylpyridine (P4VPy) to
      dimyristoylphosphatidic acid (DMPA) small unilamellar vesicles (SUVs) was studied
      as a function of pH, ionic strength (I), polymer concentration and temperature
      using spectrofluorimetry. Poly(vinylpyridine) (PVPy) data were transformed into
      association isotherms and analyzed in terms of binding and partition models. In
      the case of polyions, the inclusion of the activity coefficient in both models
      was essential. Moreover, a relating equation was proposed to compare parameters
      based on both theoretical approaches. On the basis of the results obtained, a
      model was developed to analyze polymer adsorption at the surface level, in which
      the length of the hydrophobic chain and the position of the N atom in the
      pyridinium ring play an important role. Transition temperature (Tc) for DMPA (ca.
      55 degrees C) is decreased between 15 degrees C-19 degrees C in the presence of
      PVPy. Van't Hoff isochore showed that the binding constant (KA) accounted for
      average PVPy-DMPA two-dimensional solid and liquid interactions. KA decreased
      with I in the presence of both polymers, but was more sensitive to I in the case
      of P2VPy. Likewise, the number of phospholipid heads (N) involved in the binding
      process decreased with I in the presence of PVPy. The influence of I was more
      significant on N than on KA.

PMID- 14656060
TI  - Postural control adaptation during galvanic vestibular and vibratory
      proprioceptive stimulation.
AB  - The objective for this study was to investigate whether the adaptation of
      postural control was similar during galvanic vestibular stimulation and during
      vibratory proprioceptive stimulation of the calf muscles. Healthy subjects were
      tested during erect stance with eyes open or closed. An analysis method designed
      to consider the adaptive adjustments was used to evaluate the motion dynamics and
      the evoked changes of posture and stimulation response. Galvanic vestibular
      stimulation induced primarily lateral body movements and vibratory proprioceptive
      stimulation induced anteroposterior movements. The lateral body sway generated by
      the galvanic stimulation was proportionally smaller and contained more high
      frequency movements (> 0.1 Hz) than the anteroposterior body sway induced by the
      vibratory stimulation. The adaptive adjustments of the body sway to the
      stimulation had similar time course and magnitude during galvanic and vibratory
      stimulation. The perturbations induced by stimulation were gradually reduced
      within the same time range (15-20 s) and both kinds of stimulation induced a body
      leaning whose direction was dependent on stimulus. The similarities in the
      adjustment patterns suggest that postural control operates in the same way
      independent of the receptor systems affected by the disturbance and irrespective
      of whether the motion responses were induced in a lateral or anteroposterior
      direction.

PMID- 14656059
TI  - Bayesian two-compartment and classic single-compartment minimal models:
      comparison on insulin modified IVGTT and effect of experiment reduction.
AB  - Models describing plasma glucose and insulin concentration of an intravenous
      glucose tolerance test (IVGTT) allow a noninvasive cost-effective approach to
      estimate important indexes characterizing the efficiency of glucose-insulin
      control system, i.e., glucose effectiveness (S(G)) and insulin sensitivity
      (S(I)). To overcome some limitations of the classic single compartment minimal
      model (1CMM) of glucose kinetics , a two-compartment Bayesian minimal model
      (2CBMM) has been recently proposed for the standard IVGTT. This study aims to
      assess 2CBMM ability to describe the insulin-modified IVGTT (IM-IVGTT) which is
      the protocol of choice since it allows to study insulinopenic states. Both a full
      length IM-IVGTT (240 min) as well as a reduced version (90 min) of it are
      studied. Results of the maximum a posteriori identification of IM-IVGTT (240 min)
      in 13 normals agree with those of standard IVGTT, i.e., a 42% decrease (P <
      0.002) of S(G) and a 13% increase (P < 0.006) of S(I) with respect to ICMM. When
      identified from IM-IVGTT (90 min), 2CBMM not only provides S(G) and S(I)
      estimates 46% lower (P < 0.002) and 41% higher (P < 0.002) than 1CMM ones
      respectively, but also seems to overcome some limitations of the 240 min-based
      identification that probably arise because the minimal model is unable to
      properly account for the hyperglycemic hormonal response taking place in the
      second half of IM-IVGTT.

PMID- 14656061
TI  - Skin contact forces extracted from human nerve signals--a possible feedback
      signal for FES-aided control of standing.
AB  - In this paper, information about stance related skin contact forces was extracted
      from nerve cuff electrode recordings of human neural signals. Forces measured
      under the heel during standing were scaled and applied to the innervation area of
      the sural nerve on the side of the foot using a hand held force probe. The neural
      response to the stimuli was measured with a cuff chronically implanted around the
      sural nerve in one hemiplegic person. An artificial neural network was used for
      extraction of the applied force from the recorded nerve signal. The results
      showed that it is possible to extract information about absolute skin contact
      forces from the nerve signal with an average goodness of fit of 69.3% for all
      trials and 82.2% for the more dynamic trials. This information may be applicable
      as feedback signal in control of standing.

PMID- 14656062
TI  - An integrated two-level hierarchical system for decision making in radiation
      therapy based on fuzzy cognitive maps.
AB  - The radiation therapy decision-making is a complex process that has to take into
      consideration a variety of interrelated functions. Many fuzzy factors that must
      be considered in the calculation of the appropriate dose increase the complexity
      of the decision-making problem. A novel approach introduces fuzzy cognitive maps
      (FCMs) as the computational modeling method, which tackles the complexity and
      allows the analysis and simulation of the clinical radiation procedure.
      Specifically this approach is used to determine the success of radiation therapy
      process estimating the final dose delivered to the target volume, based on the
      soft computing technique of FCMs. Furthermore a two-level integrated hierarchical
      structure is proposed to supervise and evaluate the radiotherapy process prior to
      treatment execution. The supervisor determines the treatment variables of cancer
      therapy and the acceptance level of final radiation dose to the target volume.
      Two clinical case studies are used to test the proposed methodology and evaluate
      the simulation results. The usefulness of this two-level hierarchical structure
      discussed and future research directions are suggested for the clinical use of
      this methodology.

PMID- 14656063
TI  - A novel approach for estimating muscle fiber conduction velocity by spatial and
      temporal filtering of surface EMG signals.
AB  - We describe a new method for the estimation of muscle fiber conduction velocity
      (CV) from surface electromyography (EMG) signals. The method is based on the
      detection of two surface EMG signals with different spatial filters and on the
      compensation of the spatial filtering operations by two temporal filters (with CV
      as unknown parameter) applied to the signals. The transfer functions of the two
      spatial filters may have different magnitudes and phases, thus the detected
      signals have not necessarily the same shape. The two signals are first spatially
      and then temporally filtered and are ideally equal when the CV value selected as
      a parameter in the temporal filters corresponds to the velocity of propagation of
      the detected action potentials. This approach is the generalization of the
      classic spectral matching technique. A theoretical derivation of the method is
      provided together with its fast implementation by an iterative method based on
      the Newton's method. Moreover, the lowest CV estimate among those obtained by a
      number of filter pairs is selected to reduce the CV bias due to nonpropagating
      signal components. Simulation results indicate that the method described is less
      sensitive than the classic spectral matching approach to the presence of
      nonpropagating signals and that the two methods have similar standard deviation
      of estimation in the presence of additive, white, Gaussian noise. Finally,
      experimental signals have been collected from the biceps brachii muscle of ten
      healthy male subjects with an adhesive linear array of eight electrodes. The CV
      estimates depended on the electrode location with positive bias for the estimates
      from electrodes close to the innervation or tendon regions, as expected. The
      proposed method led to significantly lower bias than the spectral matching method
      in the experimental conditions, confirming the simulation results.

PMID- 14656064
TI  - Algorithm for tissue ischemia estimation based on electrical impedance
      spectroscopy.
AB  - The purpose of this paper is to present an algorithm developed for real-time
      estimation of skeletal muscle ischemia, based on parameters extracted from in
      vivo obtained electrical impedance spectra. A custom impedance spectrometer was
      used to acquire data sets: complex impedance spectra measured at 27 frequencies
      in the range of 100 Hz-1 MHz, and tissue pH. Twenty-nine in vivo animal studies
      on rabbit anterior tibialis muscle were performed to gather data on the behavior
      of tissue impedance during ischemia. An artificial neural network (ANN) was used
      to quantitatively describe the relationship between the parameters of complex
      tissue impedance spectra and tissue ischemia via pH. The ANN was trained on 1249,
      and tested on 946 ischemic tissue impedance data sets. A correlation of 94.5% and
      a standard deviation of 0.15 pH units was achieved between the ANN estimated pH
      and measured tissue pH values.

PMID- 14656065
TI  - Statistical accuracy of a moving equivalent dipole method to identify sites of
      origin of cardiac electrical activation.
AB  - While radio frequency (RF) catheter ablation (RCA) procedures for treating
      ventricular arrhythmias have evolved significantly over the past several years,
      the use of RCA has been limited to treating slow ventricular tachycardias (VTs).
      In this paper, we present preliminary results from computer and animal studies to
      evaluate the accuracy of an algorithm that uses the single equivalent moving
      dipole (SEMD) model in an infinite homogeneous volume conductor to guide the RF
      catheter to the site of origin of the arrhythmia. Our method involves measuring
      body surface electrocardiographic (ECG) signals generated by arrhythmic activity
      and by bipolar current pulses emanating from a catheter tip, and representing
      each of them by a SEMD model source at each instant of the cardiac cycle, thus
      enabling rapid repositioning of the catheter tip requiring only a few cycles of
      the arrhythmia. We found that the SEMD model accurately reproduced body surface
      ECG signals with a correlation coefficients > 0.95. We used a variety of methods
      to estimate the uncertainty of the SEMD parameters due to measurement noise and
      found that at the time when the arrhythmia is mostly localized during the cardiac
      cycle, the estimates of the uncertainty of the spatial SEMD parameters (from ECG
      signals) are between 1 and 3 mm. We used pacing data from spatially separated
      epicardial sites in a swine model as surrogates for focal ventricular arrhythmic
      sources and found that the spatial SEMD estimates of the two pacing sites agreed
      with both their physical separation and orientation with respect to each other.
      In conclusion, our algorithm to estimate the SEMD parameters from body surface
      ECG can potentially be a useful method for rapidly positioning the catheter tip
      to the arrhythmic focus during an RCA procedure.

PMID- 14656066
TI  - Human ECoG analysis during speech perception using matching pursuit: a comparison
      between stochastic and dyadic dictionaries.
AB  - We use the matching pursuit (MP) algorithm to detect induced gamma activity in
      human EEG during speech perception. We show that the MP algorithm is particularly
      useful for detecting small power changes at high gamma frequencies (> 70 Hz). We
      also compare the performance of the MP using a stochastic versus a dyadic
      dictionary and show that despite the frequency bias the time-frequency power plot
      (averaged over 100 trials) generated by the dyadic MP is almost identical (>
      98.5%) to the one generated by the stochastic MP. However, the dyadic MP is
      computationally much faster than the stochastic MP.

PMID- 14656067
TI  - Neuropathology of cognitively normal elderly.
AB  - Despite general agreement about the boundaries of Alzheimer disease (AD),
      establishing a maximum limit for Alzheimer-type pathology in cognitively intact
      individuals might aid in defining more precisely the point at which Alzheimer
      pathology becomes clinically relevant. In this study, we examined the
      neuropathological changes in the brains of 39 longitudinally followed.
      cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median
      85 years). Neuropathological changes of the Alzheimer type were quantified by
      determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak
      and by quantification of the abundance of diffuse, cored, and neuritic plaque
      burden using the scheme developed by the Consortium to Establish a Registry for
      Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology
      were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32
      subjects (82%) with less than moderate numbers of cored plaques and 37 subjects
      (95%) with less than moderate numbers of tau-positive neuritic plaques. Many
      subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National
      Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met
      criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate
      "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met
      Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small,
      old infarcts were common, but no subjects had more than 2 of these and none had a
      single large infarction. Thus, the majority of individuals who are cognitively
      normal near the time of their death have minimal amounts of tau-positive neuritic
      pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most
      affected neocortical region). The few subjects with more severe AD pathology can
      be expected based on incidence rates of AD in the very elderly.

PMID- 14656068
TI  - Comparison of iNOS inhibition by antisense and pharmacological inhibitors after
      spinal cord injury.
AB  - Inducible nitric oxide synthase (iNOS) is a key mediator of inflammation during
      pathological conditions. We examined, through the use of selective iNOS
      inhibitors, the role of iNOS in specific pathophysiological processes after
      spinal cord injury (SCI), including astrogliosis, blood-spinal cord barrier
      (BSCB) permeability, polymorphonuclear leukocyte infiltration, and neuronal cell
      death. Administration of iNOS antisense oligonucleotides (ASOs) (intraspinally at
      3 h) or the pharmacological inhibitors, N-[3(Aminomethyl) benzyl] acetamidine
      (1400 W) (i.v./i.p. 3 and 9 h) or aminoguanidine (i.p. at 3 and 9 h) after
      moderate contusive injury decreased the number of iNOS immunoreactive cells at
      the injury site by 65.6% (iNOS ASOs), 62.1% (1400 W), or 59% (aminoguanidine) 24
      h postinjury. iNOS activity was reduced 81.8% (iNOS ASOs), 56.7% (1400 W), or
      67.9% (aminoguanidine) at this time. All iNOS inhibitors reduced the degree of
      BSCB disruption (plasma leakage of rat immunoglobulins), with iNOS ASO inhibition
      being more effective (reduced by 58%). Neutrophil accumulation within the injury
      site was significantly reduced by iNOS ASOs and 1400 W by 78.8% and 20.9%,
      respectively. Increased astrogliosis was diminished with iNOS ASOs but enhanced
      following aminoguanidine. Detection of necrotic and apoptotic neuronal cell death
      by propidium iodide and an FITC-conjugated Annexin V antibody showed that iNOS
      inhibition could significantly retard neuronal cell death rostral and caudal to
      the injury site. These novel findings indicate that acute inhibition of iNOS is
      beneficial in reducing several pathophysiological processes after SCI.
      Furthermore, we demonstrate that the antisense inhibition of iNOS is more
      efficacious than currently available pharmacological agents.

PMID- 14656069
TI  - Molecular identification of AMY, an Alzheimer disease amyloid-associated protein.
AB  - One of the neuropathological lesions characteristic of Alzheimer disease (AD) is
      the cerebral accumulation of the amyloid beta-peptide (A beta). Although numerous
      studies have demonstrated that A beta spontaneously forms amyloid in vitro, the
      molecular events underlying A beta amyloid formation in vivo are less well
      understood. Immunohistochemical studies have shown that other proteins colocalize
      with A beta in amyloid deposits in brain. The identity of one of these proteins,
      AMY, has so far remained elusive; therefore we attempted to purify AMY. The AMY
      protein was found to co-purify with A beta in insoluble fractions from human AD
      brain, and was absent in brains from control subjects. AMY immunoreactivity was
      primarily restricted to a 50-kDa and 100-kDa protein species. Interestingly, the
      chromatographic and immunological profile of AMY resembled the recently
      identified amyloid-associated protein CLAC, derived from a transmembrane collagen
      like precursor, CLAC-P. Antibodies against AMY recognized CLAC-P expressed in
      mammalian cells. In addition, side-by-side comparisons of AD brain sections and
      extracts, using antibodies against both AMY and CLAC, respectively, resulted in
      almost identical staining patterns. Therefore, we conclude that the AMY
      immunoreactivity seen in association with amyloid in AD brain is due to the
      presence of the CLAC protein.

PMID- 14656070
TI  - Clinical utility of fluorescence in situ hybridization (FISH) in morphologically
      ambiguous gliomas with hybrid oligodendroglial/astrocytic features.
AB  - Gliomas with hybrid oligodendroglial/astrocytic features are diagnostically
      problematic, and our ability to predict tumor behavior is limited. Some likely
      represent intermingled mixed oligoastrocytomas (MOAs), though precise diagnostic
      criteria and specific markers for this lesion are lacking. From the files at
      Washington University (1987-2000), 155 "ambiguous" glioma/intermingled MOA
      candidates were independently classified and graded by 5 neuropathologists, with
      consensus-derived pure oligodendrogliomas and astrocytomas excluded from further
      study. The 90 remaining cases (grades II = 29, III = 44, IV = 17) were analyzed
      by FISH on formalin-fixed, paraffin-embedded sections. Detectable deletions
      included combined 1p/19q (9%), solitary 19q (22%), PTEN/DMBT1 (26%), and p16
      (32%). EGFR amplification was found in 11%. Patients were followed until death
      (47%) or a median of 3.3 years. Similar to prior glioma series, patient age (p <
      0.0001) and tumor grade (p < 0.0001) were strongly associated with survival
      times. EGFR amplification (p = 0.0007) and deletions of PTEN/ DMBT1 (p = 0.016)
      or p16 (p = 0.014), either individually or as a group (p = 0.04), portended a
      shorter median survival compared with tumors lacking these alterations. We
      conclude that 1) distinct genetic subsets are identifiable by FISH in
      morphologically ambiguous gliomas, and 2) both histological grading and molecular
      analysis yield prognostically useful information.

PMID- 14656071
TI  - Altered corticogenesis and neuronal morphology in irradiation-induced cortical
      dysplasia: a Golgi-Cox study.
AB  - Cortical dysplasia has a strong clinical association with epilepsy and mental
      retardation, but the relationship between alterations in cortical structure and
      function in dysplasia-related disorders is poorly understood. The cerebral cortex
      of irradiated rats, an experimental model of cortical dysplasia, was studied
      using cresyl violet-stained sections and the Golgi-Cox method. The irradiated
      cortex is characterized by reductions in size, volume, and number of neurons and
      fibers reflecting the original lethal injury to neuronal precursors.
      Consequently, only neurons that survived this injury were able to continue their,
      albeit altered, development. The result is an altered corticogenesis
      characterized by neuronal, fiber circuitry, and microvascular alterations.
      Abnormal aggregates (nodules) of excitatory pyramidal neurons with altered
      dendritic profiles and functional territories are found between 200 and 400
      microm from the pial surface. Their horizontal dendritic profiles and functional
      territories contrast with the vertical (columnar) dendritic profiles and
      functional territories of normal pyramidal neurons. This horizontal concentration
      of spiny dendrites and, hence, of excitatory synaptic contacts suggests a
      response to the presence of an abnormal horizontal plexus of afferent fibers
      terminals. Stellate neurons, some morphologically compatible with inhibitory
      basket cells, are also essential components of these nodules. Some neuronal
      nodules are characterized by a rich plexus of anastomotic capillaries that
      contrasts with the sparser vasculature of surrounding gray matter tissue. The
      presence of well-vascularized aggregates of altered pyramidal and inhibitory
      neurons suggests a high level of metabolic activity. Well-vascularized deep
      heterotopias are also found. We propose that the functional activity of well
      vascularized neuronal nodules and heterotopias could play a role in the abnormal
      cortical function in this model.

PMID- 14656072
TI  - MPP+ induces the endoplasmic reticulum stress response in rabbit brain involving
      activation of the ATF-6 and NF-kappaB signaling pathways.
AB  - Inhibition of mitochondrial function and the subsequent generation of oxidative
      stress are strongly suggested to underlie MPTP/MPP+-induced neurotoxicity, which
      has been used extensively as a model for Parkinson disease. In the present study
      we have examined the hypothesis that MPP+ targets the endoplasmic reticulum.
      Because rabbits possess more genetic similarities to primates than to rodents we
      have selected this animal model system for our MPP+ neurotoxicity studies. MPP+
      was administered directly into the brain of New Zealand white rabbits via the
      intracisternal route, and the effects on tissue from the substantia nigra were
      examined. Here we demonstrate that MPP+ in a dose-dependent manner induces the
      loss of tyrosine hydroxylase activity, oxidative DNA damage, and activation of
      the endoplasmic reticulum stress response. The endoplasmic reticulum response,
      mediated by activation of ATF-6 and NF-kappaB, leads to activation of gadd 153.
      These effects correlate with the activation of caspase-3 and of c-Jun N-terminal
      kinase (JNK) kinase. We propose that pharmacological agents that inhibit the
      perturbation of endoplasmic reticulum function or the activation of JNK may
      represent a potential therapeutic approach for the prevention of neurotoxin
      induced Parkinson disease.

PMID- 14656073
TI  - Periventricular/intraventricular hemorrhage in neonatal mouse cerebrum.
AB  - Periventricular/intraventricular hemorrhage (PVH/IVH) into brain can occur in
      premature infants and is associated with poor developmental outcome. The purpose
      of this study was to develop and characterize a model of PVH/IVH in newborn
      mouse. We hypothesized that periventricular germinal matrix would exhibit reduced
      cell proliferation. PVH/IVH was induced in 1-day-old mice by injection of
      autologous blood into the periventricular tissue. Magnetic resonance images (MRI)
      were obtained from 15 minutes to 14 days later. Mice were killed 4 hours to 28
      days later. Cell proliferation, dying cells, astrocyte and microglial reactions,
      neutrophils, and lymphocytes were quantified. Histological studies showed that
      MRI accurately localizes the hematoma but overestimates its size. The hematoma,
      located in the striatum and germinal tissue, always extended into the lateral
      ventricles. Cell proliferation, measured by Ki67 immunoreactivity, was suppressed
      bilaterally in germinal matrix and beyond from 8 hours to 7 days. Increased cell
      death was observed in the ipsilateral striatum and germinal matrix 1 and 2 days
      after PVH/IVH. Astrocyte and microglia reaction peaked at 2 days and persisted up
      to 28 days. Inflammatory response was minimal. Extravasated blood might play an
      important role in brain damage following PVH/IVH through suppression of cell
      proliferation.

PMID- 14656074
TI  - The cellular and molecular pathology of the motor system in hereditary spastic
      paraparesis due to mutation of the spastin gene.
AB  - Hereditary spastic paraparesis (HSP) is a genetically heterogeneous disorder, the
      most common cause of which is mutation of the spastin gene. Recent evidence
      suggests a role for spastin in microtubule dynamics, but the distribution of the
      protein within the CNS is unknown. The core neuropathology of HSP is distal
      degeneration of the lateral corticospinal tract and of fasciculus gracilis, but
      there are few neuropathological studies of cases with a defined mutation. We
      aimed to determine the distribution of spastin expression in the human CNS and to
      investigate the cellular pathology of the motor system in HSP due to mutation of
      the spastin gene. Using an antibody to spastin, we have carried out
      immunohistochemistry on postmortem brain. We have demonstrated that spastin is a
      neuronal protein. It is widely expressed in the CNS so that the selectivity of
      the degeneration in HSP is not due to the normal cellular distribution of the
      protein. We have identified mutation of the spastin gene in 3 autopsy cases of
      HSP. Distal degeneration of long tracts in the spinal cord, consistent with a
      dying back axonopathy, was accompanied by a microglial reaction. The presence of
      novel hyaline inclusions in anterior horn cells and an alteration in
      immunostaining for cytoskeletal proteins and mitochondria indicates that long
      tract degeneration is accompanied by cytopathology in the motor system and may
      support a role for derangement of cytoskeletal function. All 3 cases also
      demonstrated evidence of tau pathology outside the motor system, suggesting that
      the neuropathology is not confined to the motor system in spastin-related HSP.

PMID- 14656075
TI  - Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden
      infant death syndrome.
AB  - The rate of the sudden infant death syndrome (SIDS) among American Indian infants
      in the Northern Plains is almost 6 times higher than in U.S. white infants. In a
      study of infant mortality among Northern Plains Indians, we tested the hypothesis
      that receptor binding abnormalities to the neurotransmitter serotonin (5-HT) in
      SIDS cases, compared with autopsied controls, occur in regions of the medulla
      oblongata that contain 5-HT neurons and that are critical for the regulation of
      cardiorespiration and central chemosensitivity during sleep, i.e. the medullary 5
      HT system. Tritiated-lysergic acid diethylamide binding to 5-HT(1A-D) and 5-HT2
      receptors was measured in 19 brainstem nuclei in 23 SIDS and 6 control infants
      using tissue receptor autoradiography. Binding in the arcuate nucleus, a part of
      the medullary 5-HT system along the ventral surface, in the SIDS infants (mean
      age-adjusted binding 7.1 +/- 0.8 fmol/mg tissue, n = 23) was significantly lower
      than in controls (mean age-adjusted binding 13.1 +/- 1.6 fmol/mg tissue, n = 5)
      (p = 0.003). Binding also demonstrated significant diagnosis x age interactions
      (p < 0.04) in 4 other nuclei that are components of the 5-HT system. These data
      suggest that medullary 5-HT dysfunction can lead to sleep-related, sudden death
      in affected SIDS infants, and confirm the same binding abnormalities reported by
      us in a larger dataset of non-American Indian SIDS and control infants. This
      study also links 5-HT abnormalities in the arcuate nucleus with exposure to
      adverse prenatal exposures, i.e. cigarette smoking (p = 0.011) and alcohol (p =
      0.075), during the periconceptional period or throughout pregnancy. Prenatal
      exposure to cigarette smoke and/or alcohol may contribute to abnormal fetal
      medullary 5-HT development in SIDS infants.

PMID- 14656076
TI  - Epigenetic silencing of the HIC-1 gene in human medulloblastomas.
AB  - The HIC-1 (hypermethylated in cancer) candidate tumor suppressor gene is located
      on chromosome 17p13.3, a region frequently deleted in medulloblastomas (MBs). MBs
      arising in the cerebellum represent the most common malignant brain tumors in
      children. In this study we have analyzed the sequence, methylation, and
      expression status of the HIC-1 gene in MBs. Hypermethylation of the 5'UTR and/or
      second exon of HIC-1 was detected in 33/39 (85%) of MB biopsies and in 7/8 (88%)
      of MB cell lines by methylation-specific PCR. There was a significant correlation
      (p < 0.001) between HIC-1 methylation and lack of transcription as determined by
      competitive RT-PCR. Treatment of the MB cell lines Daoy and MEB-MED-8A with 5-aza
      2'deoxycytidine led to re-expression of HIC-1 transcripts, indicating a silencing
      of HIC-1 by CpG island methylation. Mutation analysis of the coding region of HIC
      1 revealed a single deletion leading to an in-frame deletion of 4 amino acids in
      the second exon of HIC-1 (1/68, 1.5%). Our data indicate that a significant
      number of MBs exhibit strikingly reduced HIC-1 expression caused by altered CpG
      island methylation. These data suggest that epigenetic silencing of HIC-1 may
      well contribute to the pathogenesis in the majority of MBs.

PMID- 14656077
TI  - Total synthesis of (+)-isoschizandrin utilizing a samarium(II) iodide-promoted 8
      endo ketyl-olefin cyclization.
AB  - The 13-step synthesis of (+)-isoschizandrin reported herein features a
      samarium(II) iodide-promoted 8-endo ketyl-olefin coupling to assemble the eight
      membered ring present in the target concomitantly with the required functionality
      and stereochemistry. In constructing (+)-isoschizandrin as a single atropisomer,
      the synthesis utilizes a kinetic resolution of a seven-membered lactone using a
      CBS-oxazaborolidine.

PMID- 14656078
TI  - Synthesis of 3-aminolactams as X-Gly constrained pseudodipeptides and
      conformational study of a Trp-Gly surrogate.
AB  - 3-Amino-delta-valerolactams trans-11a-c were synthesized through conjugate
      addition and Curtius rearrangement and converted into Fmoc-[Trp-Gly], Fmoc-[Ile
      Gly], and Fmoc-[Phe-Gly] pseudodipeptides. Conformational analyses of tripeptide
      analogues Ac-[Trp-Gly]-Leu-NH(2) 17a and 17b by NMR experiments and molecular
      modeling calculations showed that diastereomer 17a adopted a gamma-turn/distorted
      type II beta-turn structure, whereas diastereomer 17b adopted mainly a gamma-turn
      structure.

PMID- 14656079
TI  - Analysis of conformational equilibria in aplidine using selective excitation 2D
      NMR spectroscopy and molecular mechanics/dynamics calculations.
AB  - Aplidine (dehydrodidemnin B), a natural product with potent antitumor activity
      currently in multicenter phase II clinical trials, exists in DMSO as a mixture of
      four slowly interconverting conformations in a ratio of 47:33:13:7. NMR
      spectroscopy shows that these arise as a consequence of cis/trans isomerization
      about the NMe-Leu(7)-Pro(8) and Pro(8)-Pyr amide bonds of the molecule's side
      chain. Two major conformations account for 47% and 33% of the total population, a
      ratio of 60:40 between the two. They correspond to the cis- and trans-isomers,
      respectively, about the Pro(8)-Pyr amide bond. Two minor conformers arise as a
      consequence of similar isomerism about the Pro(8)-Pyr amide bond, but in
      structures in which the NMe-Leu(7)-Pro(8) amide bond is cis rather than trans.
      These account for approximately 13% and 7% of the total population, corresponding
      to a ratio of 65:35 cis/trans, respectively. Molecular dynamics simulations show
      that the three-dimensional structures of all four conformational isomers are
      similar in the macrocycle and that all are essentially unchanged with respect to
      the macrocycle of didemnin B. Significant differences in the conformation of the
      molecule's side chain are, however, observed between major and minor pairs.
      Analysis of hydrogen-bonding patterns shows that each major conformer exhibits a
      beta-turn like structure and is stabilized by hydrogen bonding between a
      different carbonyl group of the pyruvyl unit of the molecule's side chain and the
      NH of the Thr(6) residue. The minor isomers have a cis-amide bond between the NMe
      Leu(7) and Pro(8) residues that obliges the side chain to adopt an extended
      disposition where hydrogen bonding to the macrocycle is absent. These results
      suggest that the ability of the molecule's side chain to adopt a beta-turn-like
      conformation may not be a prerequisite for biological activity in the didemnins
      and that conformations having an extended side-chain may play a role in the
      biological activity of aplidine.

PMID- 14656080
TI  - Palladium-catalyzed amination of aryl nonaflates.
AB  - The first detailed study of the palladium-catalyzed amination of aryl nonaflates
      is reported. Use of ligands 2-4 and 6 allows for the catalytic amination of
      electron-rich and -neutral aryl nonaflates with both primary and secondary
      amines. With use of Xantphos 5, the catalytic amination of a variety of
      functionalized aryl nonaflates resulted in excellent yields of anilines; even 2
      carboxymethyl aryl nonaflate is effectively coupled with a primary alkylamine.
      Moderate yields were obtained when coupling halo-aryl nonaflates with a variety
      of amines, where in most cases the aryl nonaflate reacted in preference to the
      aryl halide. Overall, aryl nonaflates are an effective alternative to triflates
      in palladium-catalyzed C-N bond-forming processes due to their increased
      stability under the reaction conditions.

PMID- 14656081
TI  - Synthesis of polyfunctionalized biphenyls as intermediates for a new class of
      liquid crystals.
AB  - A series of hexa- and octasubstituted biphenyls containing halogen, amino, nitro,
      and propylthio substituents were prepared by metal-mediated convergent synthesis
      from halobenzene precursors. The Pd-assisted C-C coupling methods were
      ineffective in the formation of the Ar-Ar bond except for the synthesis of 1b.
      All tetra-ortho-substituted biphenyls were prepared via Ullmann coupling
      reactions. The halogens were introduced after formation of the biphenyl by
      utilizing the directing properties of the amino group(s). In the case of 3b, a
      polyhalogenated benzene substrate was used for biphenyl formation via Ullmann
      coupling.

PMID- 14656082
TI  - On attempts at generation of carboranyl carbocation.
AB  - We have synthesized all three possible isomers of C-hydroxycarborane from the
      corresponding amines via diazotization. The O-protonated C-hydroxycarboranes were
      characterized using the NMR spectrum measurements. Attempts at generating of
      carboranyl carbocations were carried out by the solvolyses of C-tosylates and C
      triflates, as well as by treatment with superacids. Anchimeric assistance of both
      homoconjugative and hyperconjugative substituents was also investigated, as
      demonstrated by a successful strategy devised for the solvolytic generation of a
      phenyl cation. However, we have not been able to chemically provide any evidence
      of carboranyl carbocations, although the carboranyl carbocation may be an
      intermediate in the decomposition of the C-carboranediazonium ion.

PMID- 14656083
TI  - A short route toward chiral, polyhydroxylated indolizidines and quinolizidines.
AB  - In this paper, a rapid route toward functionalized bicyclic alkaloids is
      presented. In only three steps, an easily accessible carbohydrate derivative was
      converted into iodomethyl indolizidine 13, which can equilibrate to the
      corresponding iodoquinolizidine 15. We provide strong evidence that this
      equilibration proceeds via an aziridinium ion intermediate. Furthermore,
      nucleophilic substitution of the iodomethyl indolizidine as well as the
      aziridinium intermediate gives access to highly functionalized indolizidine and
      quinolizidine alkaloids.

PMID- 14656084
TI  - Improving the strategy and performance of molecularly imprinted polymers using
      cross-linking functional monomers.
AB  - A new strategy for monomer design has been investigated that combines interactive
      monomer functionality with a cross-linking format, giving as a result noncovalent
      molecularly imprinted polymers (MIPs) with improved performance. This strategy
      was explored under the premise that more functionality could be introduced
      without suffering performance losses due to reduced cross-linking. While this
      proved to be correct, equally important contributions to selectivity enhancement
      at the molecular level by conformation control and diastereomeric complexation
      were also discovered. Monomers derived from l-serine and l-aspartic acid were
      synthesized and used to prepare MIPs, with the best performance obtained for the
      MIP formulated with the serine-based cross-linker (N,O-bis-methacryloyl l-serine,
      3), versus the aspartic-acid-based cross-linkers and the traditional methacrylic
      acid/ethylene glycol dimethacrylate (MAA/EGDMA) formulation. Quantitative
      structure-selectivity relationship (QSSR) studies revealed that the improved
      performance of 3 was due to three key factors: (1) the cross-linking nature of
      this monomer; (2) control of conformational flexibility; (3) a strong influence
      of monomer chirality on enantioselectivity in MIPs.

PMID- 14656085
TI  - Synthesis of N-methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine.
AB  - N-Methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine (1)(1) is a key intermediate
      in the preparation of premafloxacin (2), which was under development as an
      antibiotic for use against pathogens of veterinary importance. This paper
      describes the development of a practical, efficient, and stereoselective process
      for the preparation of 1 from isobutyl (3S)-3-[methyl[(1S)-1
      phenylethyl]amino]butanoate (5c). The key steps in the synthetic sequence are an
      asymmetric Michael addition, which yields 5c, and a stereoselective alkylation,
      which yields (3S,4S)-3-allyl-1,4-dimethylazetidin-2-one (17).

PMID- 14656086
TI  - Steric vs hydrogen-bonding control of atropisomerization: preparation of either
      diastereomer of configurationally stable allocolchicinoids.
AB  - Steric vs hydrogen-bonding atropisomerization control of configurationally stable
      analogues of the biaryl natural product allocolchicine is described.
      Intramolecular hydrogen bonding between the C8 hydroxy group and the C7 oxygen
      functionality in (aR,7R)-diastereomer II of 2 and 4 leads to its thermodynamic
      stabilization relative to the opposite diastereomer (aR,7S)-I, which is
      manifested by the strong preference toward II under thermal equilibration
      conditions (>94% de). Protection of C8-OH removes the H-bonding and results in
      repulsive interaction between C7 and C8 functionalities, which destabilizes II.
      Steric tuning of the C8 protecting group in 7-12 allows for almost complete
      inversion of the axial configuration in 2 under thermal equilibration conditions
      (>96% de toward I). Previously unavailable phenolic allocolchicinoids (aR,7S)-2,I
      are subsequently released by deprotection.

PMID- 14656088
TI  - Transition structures, energetics, and secondary kinetic isotope effects for cope
      rearrangements of cis-1,2-divinylcyclobutane and cis-1,2-divinylcyclopropane: a
      DFT study.
AB  - The minimum energy reaction paths and secondary kinetic isotope effects (KIE) for
      the Cope rearrangements of cis-1,2-divinylcyclobutane and cis-1,2
      divinylcyclopropane obtained by (U)B3LYP calculations are reported. Both
      reactions proceed through endo-boatlike reaction paths, and have aromatic
      transition states. The predicted activation energies are in agreement with the
      experimental data. The reaction paths of the rearrangements are intervened by
      enantiomerization saddle points of the products (and the reactant in the case of
      divinylcyclobutane). The calculated KIEs are similar in the two systems, and
      consistent with the geometries of the transition structures. There is
      computational evidence that the isotope effect associated with the conversion of
      a pure sp(2) C-H bond into a pure sp(3) one might be the same in all molecules.
      The predicted KIEs agree with experiment for divinylcyclopropane, but not for
      divinylcyclobutane.

PMID- 14656087
TI  - The direct organocatalytic asymmetric mannich reaction: unmodified aldehydes as
      nucleophiles.
AB  - The unprecedented application of unmodified aldehydes as nucleophilic donors in
      direct catalytic asymmetric Mannich-type reactions is disclosed in a full
      account. Our efforts in broadening the applicability of chiral pyrrolidine-based
      catalysts in direct asymmetric Mannich-type reactions led to the highly diastereo
      and enantioselective and concise synthesis of functionalized alpha- and beta
      amino acids, beta-lactams, and amino alcohols.

PMID- 14656089
TI  - Photogeneration of o-quinone methides from o-cycloalkenylphenols.
AB  - 6-Alkylidenecyclohexa-2,4-dienones (o-quinone methides II) have been generated by
      photolysis of 2-(2'-cycloalkenyl)phenols 1 and trapped by methanol to give the
      ring-opened products 2. The best results have been obtained with the cyclohexenyl
      derivatives 1a, 1e, and 1f. In the case of the cyclopentenyl derivative 1b,
      photoproduct 2b was not observed, whereas only small amounts of 2c and 2d were
      formed from the seven- and eight-membered ring analogues 1c and 1d. Thus, ring
      size appears to be a key factor in the formation of o-quinone methides. This
      experimental result has been rationalized by means of density-functional theory
      (DFT) calculations. On the other hand, phenol substitution also appears to play a
      role in the process. Thus, electron-withdrawing groups such as CF(3) (1f)
      accelerate the reaction, whereas the opposite is true for electron-donating
      groups such as OCH(3) (1e). This is explained by an excited-state intramolecular
      proton transfer (ESIPT) mechanism, as the above results are consistent with the
      excited-state acidities of the different phenols. The lack of reactivity in the
      case of ketone 1g, where the intersystem crossing quantum yield is close to
      unity, allows us to rule out a mechanism involving the triplet state.

PMID- 14656090
TI  - Structure-activity relationship studies of illudins: analogues possessing a spiro
      cyclobutane ring.
AB  - Bicyclic and tricyclic analogues of anticancer sesquiterpene illudin S have been
      synthesized. These contain a spiro-cyclobutane instead of spiro-cyclopropane
      structure. The cytotoxicity of the former is less than that of the corresponding
      cyclopropane-containing compounds.

PMID- 14656091
TI  - Modeling the co-antioxidant behavior of monofunctional phenols. Applications to
      some relevant compounds.
AB  - A study on the regeneration of alpha-tocopherol (vitamin E) by phenolic co
      antioxidants in homogeneous hydrocarbon solution is reported. The behavior of
      some relevant phenols such as BHA, BHT, and trans-resveratrol appears to be
      nicely predicted by a model based on the knowledge of kinetic and thermochemical
      data concerning the various reactants. Despite its good reputation as an
      antioxidant, trans-resveratrol was found only moderately effective (k(inh) = 2.0
      x 10(5) M(-1) s(-1) in chlorobenzene at 303 K) and unable to recycle vitamin E.

PMID- 14656092
TI  - New Lewis-basic N-oxides as chiral organocatalysts in asymmetric allylation of
      aldehydes.
AB  - Allylation of aromatic and heteroaromatic aldehydes 1a-k with
      allyltrichlorosilane 2 can be catalyzed by the new heterobidentate, terpene
      derived bipyridine N-monoxides 4, 6a,b, and 8-11 (</=10 mol %) to afford (S)-(-)
      3 with high enantioselectivities (</=99% ee). The stereochemical outcome has been
      found to be controlled by the axial chirality of the catalyst, which in turn is
      determined by the central chirality of the annulated terpene units. Solvent
      effects on the conversion and the level of asymmetric induction have been
      elucidated, and MeCN has been identified as the optimal solvent for these
      catalysts.

PMID- 14656093
TI  - DFT studies of biarylcarbenes and the carbene-biradical continuum.
AB  - We use electronic structure modeling, mainly density functional methods, to
      characterize a variety of long-lived bisaryl triplet carbenes. The bisaryl
      systems have a triplet ground state, favored by a substantial delocalization of
      the spin into the aromatic rings. One can imagine two extreme cases of the
      bonding in these species, representable as valence isomers. In the first case,
      spin delocalization is minor and incidental; the spin is predominantly located on
      the central carbene carbon. In the second case, spins are separated by large
      distances and are found primarily on the aromatic rings; the rings are linked by
      an allenic bridge. The bisphenyl carbenes tend toward the first limit. They can
      be kinetically stabilized by ortho substituents which shield the reactive center
      and para substituents which protect that site which has substantial spin density.
      The bond angle at carbene is opened from about 142 degrees (the B3LYP/6-31G value
      for the parent bis(phenyl)carbene) to 160 degrees or more by these substituents.
      Bisanthryl carbenes illustrate the second extreme, favoring a D(2)(d)() structure
      and possessing a low-lying open shell singlet state. A hypothetical phenyl-9
      anthrylcarbine lies between the carbine and diradical extemes. The same principle
      which guides the design of stabilized diphenylcarbene carbenes and substitution
      of reactive sites by bulky protective groups serves to stabilize the bis-9
      anthrylcarbene biradical.

PMID- 14656094
TI  - Polymer-assisted solution-phase (PASP) Suzuki couplings employing an anthracene
      tagged palladium catalyst.
AB  - A general method for polymer-assisted solution-phase (PASP) Suzuki reactions
      employing a combination of anthracene-tagged palladium catalyst and anthracene
      tagged boronic acid with a polymer-supported carbonate base is reported. The
      anthracene-tagged catalyst allows for the easy removal of the Pd catalyst along
      with the dissociated phosphine ligand and phosphine oxide byproducts by
      sequestration through a chemoselective Diels-Alder reaction with a maleimide
      resin. The polymer-supported carbonate base facilitates the removal of excess
      boronic acid and the borane-containing byproducts present at the end of the
      coupling reaction. The Suzuki coupling reaction can be efficiently conducted by
      using combinations of the anthracene-tagged Pd catalyst, polymer-supported
      carbonate base, and anthracene-tagged boronic acid to yield the desired product
      in high purity and yield without the use of chromatography.

PMID- 14656095
TI  - Synthesis of cryptophycins via an N-acyl-beta-lactam macrolactonization.
AB  - An efficient and concise approach to the synthesis of the macrolide core of the
      cryptophycins has been developed. A novel macrolactonization utilizing a reactive
      acyl-beta-lactam intermediate incorporates the beta-amino acid moiety within the
      16-membered macrolide core. This modular approach, involving a cyanide-initiated
      acyl-beta-lactam ring opening followed by cyclization, was successfully applied
      to the total synthesis of cryptophycin-24. The strategy was also used in an
      efficient synthesis of the 6,6-dimethyl-substituted dechlorocryptophycin-52. In
      this case, the cyanide-initiated ring opening of the bis-substituted 2
      azetidinone followed by macrolactonization was achieved through a catalytic
      process.

PMID- 14656097
TI  - Monomeric rhodium(II) catalysts for the preparation of aziridines and
      enantioselective formation of cyclopropanes from ethyl diazoacetate at room
      temperature.
AB  - A family of bis(oxazoline) complexes of coordinatively unsaturated monomeric
      rhodium(II) (2a,b, 3a,b) are described. These complexes serve as catalysts for
      cyclopropanation of olefins by ethyl diazoacetate, giving excellent yields (66
      94%). Enantioselectivities for the cis product isomers are good (61-84%). The
      reaction shows an unusual preference for formation of the cis isomers. Catalytic
      aziridination of N-aryl imines with ethyl diazoacetate is also described.

PMID- 14656096
TI  - Synthesis of poly(propyl ether imine) dendrimers and evaluation of their
      cytotoxic properties.
AB  - In this paper, we report the synthesis of several poly(propyl ether imine)
      dendrons and dendrimers. These dendrons and dendrimers were constructed by
      involving an ether as the linker component and an imine as the branching
      component. The divergent syntheses of dendrons and dendrimers were established
      with the aid of two alternate Michael addition reactions and two alternate
      reduction reactions in a four-step iterative synthetic sequence. Dendrons up to
      three generations were synthesized and some of the dendrons were attached to a
      benzenoid core so as to obtain dendrimers up to two generations containing 12
      carboxylic acids at the periphery. Divergent synthesis involving ether as the
      core was found to be more facile, and dendrimers up to three generations having
      16 carboxylic acids at the periphery were achieved in good to excellent yields in
      each individual step. The adopted synthetic sequence allows us to install either
      alcohol, an amine, or a carboxylic acid at their peripheries. The carboxylic acid
      terminated dendrons and dendrimers were evaluated as to their cytotoxic
      properties, and while most dendrons and dendrimers did not exhibit any measurable
      cytotoxicity, even up to 100 microg/mL, the second-generation dendrimer with the
      benzenoid core exhibited a mild toxicity at concentrations above 30 microg/mL.

PMID- 14656098
TI  - Effects of an electron-withdrawing group on thermal decomposition of 4-alkylidene
      1-pyrazolines: a novel stereoselective formation of alkylidenecyclopropane due to
      participation of pi-electrons on the methylene carbon in decomposition.
AB  - Thermal decomposition of 4-alkylidenepyrazolines 14 bearing a methoxycarbonyl
      group at C-3, prepared by 1,3-dipolar cycloaddition between allenecarboxylates 12
      and diazoalkanes 13, was carried out. Unlike normal 4-alkylidenepyrazolines,
      which decompose in stepwise mechanisms at high temperatures, 14 decomposed
      concertedly at moderately low temperatures (45-110 degrees C), resulting in
      selective formation of the two isomeric alkylidenecyclopropanes 7 arising from
      the bond formation between the exo-methylene carbon and the 5-carbon. The
      selective formation and the configurations of the products are rationalized in
      terms of the concerted process via the folded conformation of the pyrazolines.
      Introduction of an electron-withdrawing group at the 3-position of the 4
      alkylidenepyrazoline system causes the polarization of the C(3)-N(2) bond
      inducing the properties of intramolecular diazonium salt 8, in which the pi
      electrons on the methylene carbon become more nucleophilic and participate in the
      cleavage of the C(5)-N(1) bond. The X-ray crystal structure of the typical normal
      alkylidenepyrazoline 14a with only small steric interactions between the
      substituents was determined to be a nearly planar ring structure.

PMID- 14656099
TI  - Asymmetric alkylation of N-toluenesulfonylimines with dialkylzinc reagents
      catalyzed by copper-chiral amidophosphine.
AB  - The synthetic procedure of a chiral amidophosphine ligand 5 bearing two bulky
      substituents, 2,4,6-trimethylphenylmethyl or 2,4,6-triisopropylphenylmethyl
      groups, on the pyrrolidine ring was improved by employing the borane-THF
      reduction of the lactam-alcohol intermediate 8. The resulting amino alcohol was
      selectively acylated to give an amide-alcohol 11, which was then converted to the
      chloride 12 in 55-73% yields by the treatment with methanesulfonyl chloride in
      collidine. The reaction of the chloride 12 with NaPPh(2) in dioxane-THF gave an
      amidophosphine 5 in an acceptably high 82-83% yields. Addition of a hexane
      solution of dialkylzinc reagent to a mixture of catalytic amount of an
      amidophosphine 5, copper species, and N-toluenesulfonylimine 1a of benzaldehyde
      in toluene provided a solution which gave the alkylated amide 3 in high yield and
      enantioselectivity up to 96%. A survey of copper sources and solvents concluded
      that copper(II) ditriflate and copper(I) triflate-benzene complex as good copper
      sources and toluene as a choice of solvent. N-Toluenesulfonylimines 1a-e of
      arylaldehydes, furfural, and alkanals were successfully ethylated with
      diethylzinc to give the corresponding N-toluenesulfonylamides 3aE-eE in
      satisfactorily good 69-97% yields and high 86-96% enantioselectivities.

PMID- 14656100
TI  - New synthetic approach to cyclopenta-fused heterocycles based upon a mild Nazarov
      reaction.
AB  - The Pd-catalyzed coupling reaction of lactam or lactone-derived vinyl triflates
      and phosphates with alpha-alkoxydienylboronates gives conjugated alkoxytrienes in
      which one of the double bonds is embedded in a heterocyclic moiety. If subjected
      to mild acidic hydrolysis, these compounds undergo a 4pi electrocyclization
      process (Nazarov reaction) which furnishes cyclopenta-fused O- and N-heterocycles
      in good yields. The scope of the work has been that of closely examining the role
      and effect of both the heteroatom and the heterocycle ring size on the outcome of
      the electrocyclization, as well as the torquoselectivity of this process. The
      presence of the heteroatom was essential in stabilizing the oxyallyl cation
      intermediate, thus allowing the reaction to occur. The ring size was also a basic
      parameter in the cyclization step: five-membered azacycles required more drastic
      conditions to give 5-5 fused systems and did so only after an initial hydrolysis
      to the corresponding divinyl ketones. As for the torquoselectivity, with both 2
      methyl and 4-methyl substituted lactam derivatives steric interactions seem to
      have a role in forcing the conrotatory process to take place in one sense only:
      allowing the synthesis of diastereomerically pure compounds to be realized.
      Because different patterns of substitution on the heterocycle are compatible with
      the reaction conditions, the methodology developed could be very useful for the
      synthesis of natural products and biologically active compounds containing
      cyclopenta-fused O- and N-heterocycle moieties.

PMID- 14656101
TI  - Chemoselective, regioselective, and E/Z-diastereoselective synthesis of 2
      alkylidenetetrahydrofurans by sequential reactions of ambident dianions and
      monoanions.
AB  - A number of novel beta-ketoesters were prepared by regioselective alkylation
      reactions of simple beta-ketoester dianions. The cyclization of the dianions of
      these 1,3-dicarbonyl derivatives with 1-bromo-2-chloroethane afforded a variety
      of 2-alkylidenetetrahydrofurans with very good regioselectivity and E/Z
      diastereoselectivity. These products were deprotonated to give novel ambident
      carbanions. The alkylation of these carbanions with alkyl halides proceeded with
      very good regioselectivity and E/Z-diastereoselectivity and allowed a convenient
      synthesis of a great variety of new 2-alkylidenetetrahydrofurans.

PMID- 14656103
TI  - Synthesis, stabilities, and redox behavior of Di(1-azulenyl)(6-azulenyl)methylium
      hexafluorophosphates. Generation of a donor-acceptor-substituted neutral radical
      by azulenes.
AB  - Several di(1-azulenyl)(6-azulenyl)methanes and 1,3-bis[(1-azulenyl)(6
      azulenyl)methyl]azulenes were prepared by the condensation reaction of azulenes
      with diethyl 6-formylazulene-1,3-dicarboxylate under acidic conditions. The
      products were converted into di(1-azulenyl)(6-azulenyl)methylium
      hexafluorophosphates and azulene-1,3-diylbis[(1-azulenyl)(6-azulenyl)methylium]
      bis(hexafluorophosphate)s via hydride abstraction reaction with DDQ following the
      exchange of counterions. These mono- and dications exhibited high stability with
      large pK(R)(+) values (5.6-10.1), despite the captodative substitution of
      azulenes. The electrochemical reduction of the monocations upon cyclic
      voltammetry (CV) exhibited a reversible two-step, one-electron reduction wave
      with a small difference between the first reduction potential (E(1)(red)) and the
      second one (E(2)(red)), which exhibited the generation of highly amphoteric
      neutral radicals in solution. The electrochemical reduction of dications showed
      voltammograms, which were characterized by subsequent two single-electron waves
      and a two-electron transfer upon CV attributable to the formation of a radical
      cation, a diradical (or twitter ionic structure), and a dianionic species,
      respectively. Formation of a persistent neutral radical from a monocation was
      revealed by ESR and UV-vis spectroscopies and theoretical calculations. The ESR
      spectra of the neutral radical gave two hyperfine coupling constants: a(H) =
      0.083 (6H) and 0.166 mT (9H) (g = 2.0024), indicating that an unpaired electron
      delocalizes over all three of the azulene rings. The stable monoanion, which
      shows the localization of the charge on the 6-azulenyl substituent, was also
      successfully generated from the di(1-azulenyl)(6-azulenyl)methane derivative.

PMID- 14656102
TI  - N-tritylprolinal: an efficient building block for the stereoselective synthesis
      of proline-derived amino alcohols.
AB  - N-Tritylprolinal (prepared in four steps from l-proline) shows a very high Felkin
      diastereoselectivity in its reaction with various nucleophiles, leading to a
      straightforward and highly stereoselective access to syn-proline-derived amino
      alcohols.

PMID- 14656104
TI  - Preparation of 10-trifluoromethyl artemether and artesunate. Influence of
      hexafluoropropan-2-ol on substitution reaction.
AB  - To prepare 10-trifluoromethyl analogues of important antimalarials such as
      artemether and artesunate, the substitution reaction of the 10-trifluoromethyl
      hemiketal 6 and bromide 4 derived from artemisinin was investigated. While 6
      appeared to be unreactive under various conditions, bromide 4 could easily
      undergo substitution with methanol under electrophilic assistance or noncatalyzed
      conditions. Optimization of the reaction revealed the role of CH(2)Cl(2) as
      solvent to avoid the competitive elimination process and the crucial influence of
      hexafluoro-2-propanol (HFIP) in increasing the rate and the stereoselectivity of
      the substitution reaction (de >98%). The efficiency of this reaction was
      exemplified with various alcohols and carboxylates (yield up to 89%).

PMID- 14656105
TI  - New convergent synthesis of 1alpha,25-dihydroxyvitamin D3 and its analogues by
      Suzuki-Miyaura coupling between A-ring and C,D-ring parts.
AB  - A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D(3) and
      its analogues has been developed that involves efficient preparation of the A
      ring part 1a, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2
      methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura
      coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)
      5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through
      a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was
      treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)
      (1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert
      butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which 1a was obtained
      in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs(2)CO(3).
      The resulting A-ring intermediate 1a was reacted with alkenylboronate 12 in the
      presence of a PdCl(2)(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D(3)
      in 82% yield after protodesilylation. Similarly, all of the other three possible
      stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3
      epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D(3) were synthesized by coupling
      with 12 in excellent yield, respectively. Starting from 1a and 1c, des-C,D
      1alpha,25-dihydroxyvitamin D(3) analogues, retiferol 13 and its 3-epi derivative,
      were also prepared, respectively.

PMID- 14656106
TI  - Diastereoselective 14beta-hydroxylation of baccatin III derivatives.
AB  - 14beta-Hydroxybaccatin III, a compound with limited availability by natural
      sources, is the starting material for the synthesis of the second-generation
      anticancer taxoid ortataxel. The 7-tert-butoxycarbonyl (1a) and 7-triethylsilyl
      (1b) derivatives of 14beta-hydroxybaccatin III 1,14-carbonate were synthesized
      from 10-deacetylbaccatin III (3). The crucial steps were (a) the C(14)beta
      hydroxylation of the corresponding 13-oxobaccatin III derivatives by oxaziridine
      mediated electrophilic oxidation and (b) the reduction of the C(13) carbonyl
      group with sodium or alkylammonium borohydrides. This protocol provides a
      practical way for the semisynthesis of ortataxel from 10-deacetylbaccatin III, a
      compound readily available from various yews.

PMID- 14656107
TI  - A theoretical rationalization of the asymmetric induction in sulfinyl-directed
      [5C + 2C] intramolecular cycloadditions.
AB  - A computational DFT examination (B3LYP/6-31G and B3LYP/6-311+G//B3LYP/6-31G) of
      the thermal [5C + 2C] cycloaddditions of 6-acetoxy-3-pyranones and 3-silyloxy-4
      pyrones with tethered alkenyl sulfoxides confirms that the high level of
      diastereofacial selectivity obtained is ultimately due to the preference of the
      alkenesulfinyl group to adopt a well-defined conformation in the transition state
      of the reaction. This conformation, which is different from that found in the
      ground state, is most probably dictated by dipolar interaction effects between
      the sulfoxide and the oxidopyrylium ylide intermediate.

PMID- 14656108
TI  - Amphiphilic diblock dendrimers with a fullerene core.
AB  - Amphiphilic dendrimers with a C(60) core have been obtained by cyclization of
      dendritic 1,3-phenylenebis(methylene)-tethered bis-malonate derivatives at the
      carbon sphere. The relative position of the two cyclopropane rings in the
      resulting bis-methanofullerene derivatives has been determined based on the
      molecular symmetry (C(s)()) deduced from the (1)H and (13)C NMR spectra. The
      hydrophobic-hydrophilic balance of these dendrimers has been systematically
      modified by changing the size of the polar headgroup in order to investigate the
      role of the amphiphilicity both at the air-water interface and during deposition
      onto solid substrates. Langmuir studies have revealed a conformational change in
      the dendritic structure with the size of the polar headgroup. Because of a better
      anchoring onto the water surface, the compounds with the largest polar headgroup
      adopt a more compact structure and the dendritic branches are forced to wrap the
      fullerene core. This model is nicely confirmed by the amount of fullerene
      fullerene interactions within the Langmuir-Blodgett films as deduced from their
      absorption spectra.

PMID- 14656109
TI  - Bidentate ligands capable of variable bond angles in the self-assembly of
      discrete supramolecules.
AB  - Flexible donor ligands like 1,2-bis(3-pyridyl)ethyne or 1,4-bis(3-pyridyl)-1,3
      butadiyne self-assemble into discrete supramolecules instead of infinite networks
      upon combination with organoplatinum 90, 120, and 180 degree acceptor units.
      These systems are unique examples of versatile pyridine donors adjusting their
      bonding directionality to accommodate rigid platinum acceptors in the formation
      of closed macrocycles.

PMID- 14656110
TI  - Synthesis and optical properties of polyphenylene dendrimers based on perylenes.
AB  - A series of polyphenylene-dendronized perylenes have been synthesized, and their
      physical and mesoscopic properties have been investigated. The attached
      polyphenylene dendrons have significant effects on the physical properties of the
      perylenes. They increase the solubility of perylenes in common organic solvents,
      suppress significantly the aggregation of the perylene core, and lead to red
      shifted absorption and emission. The polyphenylene dendrons give rise to a strong
      absorption band in the UV region and exhibit efficient intramolecular energy
      transfer to the perylene moiety. The functionalization of perylenes with
      polyphenylene dendrons allows the preparation of films by spin-coating.

PMID- 14656111
TI  - Design of a new and highly effective chiral auxiliary for Diels-Alder reaction of
      1-aminodiene.
AB  - A theoretical investigation of the facial selectivity of optically active
      oxazolidin-2-one-substituted dienes has been realized. This analysis enabled the
      development of (R)-4-phenyloxazolidin-2-thione as a very effective chiral
      auxiliary for cycloaddition of 1-aminodiene.

PMID- 14656112
TI  - Effect of ring fusion on the electronic absorption and emission properties of
      oligothiophenes.
AB  - A series of fused-ring oligothiophenes were synthesized by a combination of
      Stille and oxidative coupling reactions. Compounds with the same number of double
      bonds, but varying in extent of planarization, display a similar longest
      wavelength absorption maximum in solution. However, the introduction of sulfur
      linkages into these oligothiophenes leads to a blue shift of the maximum emission
      wavelength and a correspondingly smaller Stokes shift.

PMID- 14656113
TI  - Epoxidation of chiral camphor N-enoylpyrazolidinones with
      methyl(trifluoromethyl)dioxirane and urea hydrogen peroxide/acid anhydride:
      reversal of stereoselectivity.
AB  - Both diastereomeric isomers of epoxides with high optical purity are obtained
      when camphor N-methacryloylpyrazolidinone (1a) and N-tigloylpyrazolidinone (1b)
      are treated with a urea hydrogen peroxide/TFAA and
      methyl(trifluoromethyl)dioxirane, respectively.

PMID- 14656114
TI  - Molecular recognition of alkylammonium contact ion-pairs using a ditopic
      receptor.
AB  - A ditopic, macrobicyclic receptor with adjacent anion and cation binding sites is
      able to distinguish between various monoalkylammonium salts by binding them as
      contact ion-pairs. The affinity for linear n-propylammonium chloride is at least
      2 orders of magnitude greater than that for n-propylammonium acetate, n
      propylammonium p-toluenesulfonate, and branched isopropylammonium chloride. An X
      ray structure of the receptor complexed with methylammonium chloride illuminates
      the basis of the molecular recognition.

PMID- 14656115
TI  - The first nonempirical circular dichroism determination of the absolute
      configuration of N-phthalimidosulfoximines based on exciton coupling mechanism
      and a correlation with the absolute configuration of chiral sulfoxides.
AB  - A simple nonempirical method for the assignment of absolute configuration of N
      phthalimidosulfoximines and related S-chiral sulfoxides, based on exciton-coupled
      circular dichroism, is presented.

PMID- 14656116
TI  - Enantioselective synthesis of (+)-cryptophycin 52 (LY355703), a potent
      antimitotic antitumor agent.
AB  - A highly enantioselective and convergent synthesis of cryptophycin 52 (2), an
      exceedingly potent cytotoxic agent, is described. Cryptophycin 52, a synthetic
      variant of the cryptophycin family, is currently undergoing clinical trials. The
      synthesis is convergent and involves assembly of three fragments, phenyl hexenal
      3, d-tyrosine phosphonate 4, and protected beta-amino acid derivative 5. The
      synthesis of fragment 3 involves an efficient and stereocontrolled construction
      of both stereogenic centers at C-3 and C-4 by cleavage of a substituted
      tetrahydrofuran ring via an acyloxycarbenium ion intermediate. Both of these
      stereogenic centers were derived from optically active 4-phenylbutyrolactone,
      synthesized enantioselectively by Corey-Bakshi-Shibata reduction.

PMID- 14656117
TI  - Hydroperoxide and endoperoxide lactones from photooxygenation of 3
      alkylidenedihydrofuran-2,4-diones.
AB  - 3-Alkylidenedihydrofuran-2,4-diones 1 can be photooxygenated with O(2)/TBHP to
      hydroperoxides 3 which slowly decompose to diols 5. Stable endoperoxides 4 are
      best prepared by photooxygenation of 1 with 2 equiv of O(2) in the presence of
      CuSO(4) and p-TosOH following a nonradical mechanism. They are rapidly reduced by
      anhydrous FeBr(2) to give butenolide 9 indicating a potential antimalarial
      activity.

PMID- 14656118
TI  - Direct radical polymerization of 4-styryldiphenylphosphine: preparation of cross
      linked and non-cross-linked triphenylphosphine-containing polystyrene polymers.
AB  - We report herein a simple synthesis of 4-styryldiphenylphosphine and the radical
      copolymerization of it with styrene, both with and without a cross-linker, to
      directly form cross-linked and non-cross-linked polystyrene supported
      triphenylphosphine in which the level of phosphine incorporation can be easily
      and accurately controlled. The utility of these polymers is demonstrated by their
      use in Mitsunobu and alcohol bromination reactions.

PMID- 14656119
TI  - Synthesis of macrocyclic peptide analogues of proteasome inhibitor TMC-95A.
AB  - The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as
      potential proteasome inhibitors is described. The key step involves a Ni(0)
      mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side
      chains for the formation of the biaryl junction. In addition, an enantioselective
      preparation of l-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell
      alkylation of the glycine benzophenone imine was achieved in good overall yield
      with very high ee (>85%) on a multigram scale.

PMID- 14656120
TI  - Expanding the genetic alphabet: non-epimerizing nucleoside with the pyDDA
      hydrogen-bonding pattern.
AB  - 6-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)-5-nitro-1H-pyridin-2-one (4), a C
      glycoside exhibiting the nonstandard pyDDA hydrogen-bonding pattern, was
      synthesized via Heck coupling. The nitro group greatly enhances the stability of
      the nucleoside toward acid-catalyzed epimerization without leading to significant
      deprotonation of the heterocycle at physiological pH. These results make
      nucleoside 4 a promising candidate for an expanded genetic alphabet.

PMID- 14656121
TI  - Synthesis and investigation of novel branched PEG-based soluble polymer supports.
AB  - The efficient synthesis of a number of novel poly(ethylene glycol)-based branched
      soluble polymer supports with high loading capacities has been developed. These
      compounds are characterized and tested for their loading levels utilizing a
      number of coupling reactions.

PMID- 14656122
TI  - Efficient N-demethylation of opiate alkaloids using a modified nonclassical
      Polonovski reaction.
AB  - A modified Polonovski reaction has been employed to N-demethylate several opiate
      alkaloids in moderate to high yield. This method provides an alternative to
      traditional N-demethylation procedures which utilize toxic reagents such as
      cyanogen bromide or expensive reagents such as vinyl chloroformate. The current
      synthesis involves N-oxide formation, isolation of the corresponding N-oxide
      hydrochloride, and an FeSO(4).7H(2)O mediated Polonovski reaction to afford the
      desired secondary amine.

PMID- 14656123
TI  - Synthesis of optically active atropisomeric anilide derivatives through
      diastereoselective N-allylation with a chiral Pd-pi-allyl catalyst.
AB  - N-Allylation of o-tert-butyl anilides derived from o-tert-butyl aniline and (S)
      lactic acid or (S)-mandelic acid proceeded with high diastereoselectivity in the
      presence of a (BINAP)Pd-pi-allyl catalyst to give atropisomeric N-allyl o-tert
      butyl anilide derivatives.

PMID- 14656124
TI  - Facile synthesis of alpha,alpha-diisobutylglycine and anchoring its derivatives
      onto PAL-PEG-PS resin.
AB  - alpha,alpha-Diisobutylglycine has been synthesized using a Pd-mediated
      dialkylation of ethyl nitroacetate as a key first step. The free alphaalphaAA is
      N(alpha)-protected and has been applied to the assembly of conformationally
      constrained peptide analogues. Mixed anhydrides from BOP-Cl and Fmoc-alphaalphaAA
      OH are used for anchoring alphaalphaAAs onto a trialkoxybenzyl linker on PEG-PS
      grafted support, upon which a beta-strand mimic with difficult sequence is
      assembled in a superior quality.

PMID- 14656125
TI  - Novel synthesis of conjugated dienes attached to a quaternary carbon center via
      Pd(0)-catalyzed deconjugative allylation of alkenylidenemalonates.
AB  - Palladium(0)-catalyzed deconjugative allylation of alkenylidenemalonates and
      alkylidenemalonates was achieved for the first time. Reactions of dimethyl 2-((E)
      but-2-enylidene)malonate with various allylic acetates using LHMDS as a base in
      DMF in the presence of Pd(2)dba(3) (2.5 mol %) and PPh(3) (10 mol %) proceeded at
      room temperature to give the corresponding alpha-allylation products in good
      yields in a regio- and stereoselective manner. This reaction can also be used for
      allylation of dimethyl ethylidenemalonate or dimethyl 2-((E)-pent-2
      enylidene)malonate and give the desired alpha-allylation products in good yields.

PMID- 14656126
TI  - New synthesis of optically active 5-isoxazolidinones and beta-amino acids.
AB  - A new simple and stereoselective synthesis of 5-isoxazolidinones based on the
      reaction of lithiated 2-isopropyl-2-oxazolines with nitrones is described. A
      chiral version of such a methodology allows the preparation of highly
      enantioenriched 5-isoxazolidinones which are useful precursors for the synthesis
      of beta-amino acids

PMID- 14656127
TI  - A general synthesis of N-hydroxyindoles.
AB  - A general method for the formation of N-hydroxyindoles is demonstrated through a
      lead-promoted intramolecular reductive cyclization of o-nitrobenzyl ketones and
      aldehydes under transfer hydrogenation conditions. The N-hydroxyindoles are
      isolated in high purity and excellent yield (>90%) in an operationally simple
      procedure. This new method is exemplified by a two-step synthesis of the
      naturally occurring 1-methoxyindole-3-carboxaldehyde, which is pivotal in many
      alkaloid total syntheses.

PMID- 14656128
TI  - New role of CO2 as a selective agent in palladium-catalyzed reductive Ullmann
      coupling with zinc in water.
AB  - Carbon dioxide was found to promote the palladium-catalyzed zinc-mediated
      reductive Ullmann coupling of aryl halides. In the presence of carbon dioxide,
      Pd/C, and zinc, various aromatic halides including less reactive aromatic
      chlorides were coupled to give the corresponding homocoupling products in good
      yields.

PMID- 14656129
TI  - Polymeric phosphine ligand from ring-opening metathesis polymerization of a
      norbornene derivative. Applications in the Heck, Sonogashira, and Negishi
      reactions.
AB  - The phosphine-containing polymer 1 is obtained by ruthenium-catalyzed ring
      opening metathesis polymerization of the norbornene derivative 2. Polymer 1 is
      employed as the polymer support in the palladium-catalyzed Heck, Sonogashira, and
      Negishi reactions, and the corresponding (methoxymethylphenyl)diphenylphosphine
      (6) ligand is used for comparison. The polymer-supported catalysts retain most of
      their catalytic activities in these coupling reactions in the recycling
      processes.

PMID- 14656132
TI  - Geranium leaf assisted biosynthesis of silver nanoparticles.
AB  - Development of biologically inspired experimental processes for the synthesis of
      nanoparticles is evolving into an important branch of nanotechnology. In this
      paper, we report on the use of Geranium (Pelargonium graveolens) leaf extract in
      the extracellular synthesis of silver nanoparticles. On treating aqueous silver
      nitrate solution with geranium leaf extract, rapid reduction of the silver ions
      is observed leading to the formation of highly stable, crystalline silver
      nanoparticles in solution. Transmission electron microscopy analysis of the
      silver particles indicated that they ranged in size from 16 to 40 nm and were
      assembled in solution into quasilinear superstructures. The rate of reduction of
      the silver ions by the geranium leaf extract is faster than that observed by us
      in an earlier study using a fungus, Fusarium oxysporum, thus highlighting the
      possibility that nanoparticle biosynthesis methodologies will achieve rates of
      synthesis comparable to those of chemical methods. This study also represents an
      important advance in the use of plants over microorganisms in the biosynthesis of
      metal nanoparticles.

PMID- 14656133
TI  - Enzymatic synthesis of 3'-hydroxyacetaminophen catalyzed by tyrosinase.
AB  - 3'-Hydroxyacetaminophen, a catechol metabolite of N-acetyl-p-aminophenol
      (acetaminophen) and N-acetyl-m-aminophenol (a structural analogue of
      acetaminophen and considered as a possible alternative because it is not
      hepatotoxic), is enzymatically synthesized for the first time using mushroom
      tyrosinase. Although reported to be weakly hepatotoxic in vivo, this catechol
      derivative of acetaminophen is not commercially available. This compound was
      obtained from its monophenolic precursor, acetaminophen, using the enzyme
      tyrosinase in the presence of an excess of ascorbic acid, thus reducing back the
      o-quinone product of catalytic activity to the catechol acetaminophen derivative.
      A mathematical model of the system is proposed, which is also applicable to the
      tyrosinase-mediated synthesis of any o-diphenolic compound from its corresponding
      monophenol. This synthesis procedure is continuous, easy to perform and control,
      and adaptable to a bioreactor with the immobilized enzyme for industrial purposes
      in a nonpolluting way.

PMID- 14656134
TI  - Improving the industrial production of 6-APA: enzymatic hydrolysis of penicillin
      G in the presence of organic solvents.
AB  - The hydrolysis of penicillin G in the presence of an organic solvent, used with
      the purpose of extracting it from the culture medium, may greatly simplify the
      industrial preparation of 6-APA. However, under these conditions, PGA immobilized
      onto Eupergit displays very low stability (half-life of 5 h in butanone-saturated
      water) and a significant degree of inhibition by the organic solvent (30%). The
      negative effect of the organic solvent strongly depended on the type of solvent
      utilized: water saturated with butanone (around 28% v/v) had a much more
      pronounced negative effect than that of methylisobutyl ketone (MIBK) (solubility
      in water was only 2%). These problems were sorted out by using a new penicillin G
      acylase derivative designed to work in the presence of organic solvents (with
      each enzyme molecule surrounded by an hydrophilic artificial environment) and a
      suitable organic solvent (MIBK). Using such solvent, this derivative kept its
      activity unaltered for 1 week at 32 degrees C. Moreover, the enzyme activity was
      hardly inhibited by the presence of the organic solvent. In this way, the new
      enzyme derivative thus prepared enables simplification of the industrial
      hydrolysis of penicillin G.

PMID- 14656135
TI  - Continuous D-tagatose production by immobilized thermostable L-arabinose
      isomerase in a packed-bed bioreactor.
AB  - D-Tagatose was continuously produced using thermostable L-arabinose isomerase
      immobilized in alginate with D-galactose solution in a packed-bed bioreactor.
      Bead size, L/D (length/diameter) of reactor, dilution rate, total loaded enzyme
      amount, and substrate concentration were found to be optimal at 0.8 mm, 520/7 mm,
      0.375 h(-1), 5.65 units, and 300 g/L, respectively. Under these conditions, the
      bioreactor produced about 145 g/L tagatose with an average productivity of 54 g
      tagatose/L x h and an average conversion yield of 48% (w/w). Operational
      stability of the immobilized enzyme was demonstrated, with a tagatose production
      half-life of 24 days.

PMID- 14656136
TI  - Accelerating enzymatic hydrolysis of chitin by microwave pretreatment.
AB  - Response surface analysis was used to determine optimum conditions [2% (w/v)
      chitin, 57.5 degrees C, 38 min] for microwave irradiation of chitin to improve
      its enzymatic hydrolysis. V(max)/K(m) of cabbage chitinase toward untreated and
      microwave-irradiated chitin was found to be 21.1 and 31.7 nmol h(-1) mg(-2) mL,
      respectively. Similar improvement was observed in the case of pectinase in its
      unusual catalytic activity of chitin degradation. It was found that a greater
      extent of chitin hydrolysis by chitinase was possible after the substrate chitin
      was irradiated with microwaves.

PMID- 14656137
TI  - A smart bioconjugate of alginate and pectinase with unusual biological activity
      toward chitosan.
AB  - The commercial preparation of pectinase (Pectinex Ultra SP-L) was conjugated to
      alginate by noncovalent interactions by employing 1% alginate during the
      conjugation protocol. The optimum "immobilization efficiency" was 0.76. The pH
      optimum and the thermal stability of the enzyme remained unchanged upon
      conjugation with alginate. The soluble bioconjugate showed a 3-fold increase in
      V(max)/K(m) as compared to the free enzyme when the smart biocatalyst was used
      for chitosan hydrolysis. Time course hydrolysis of chitosan thus showed higher
      conversion of chitosan into reducing oligosaccharides/sugars. The smart
      bioconjugate could be reused five times without any detectable loss of
      chitosanase activity.

PMID- 14656138
TI  - Candida bombicola cells immobilized on patterned lipid films as enzyme sources
      for the transformation of arachidonic acid to 20-HETE.
AB  - Preparation of biocompatible surfaces for immobilization of enzymes and whole
      cells is an important aspect of biotechnology due to their potential applications
      in biocatalysis, biosensing, and immunological applications. In this report,
      patterned thermally evaporated octadecylamine (ODA) films are used for the
      immobilization of Candida bombicola cells. The attachment of the cells to the ODA
      film surface occurs possibly through nonspecific interactions such as hydrophobic
      interactions between the cell walls and the ODA molecules. The enzyme cytochrome
      P450 present in the immobilized yeast cells on the ODA film surface was used for
      the transformation of the arachidonic acid to 20-hydroxyeicosatetraenoic acid (20
      HETE). The assembly of cells on the hydrophobic ODA surface was confirmed by
      quartz crystal microgravimetry (QCM), Fourier transform infrared spectroscopy
      (FTIR), and scanning electron microscopy (SEM). SEM images confirmed the strong
      binding of the yeast cells to the ODA film surface after biocatalytic reactions.
      Moreover, the biocomposite films could be easily separated from the reaction
      medium and reused.

PMID- 14656139
TI  - Lipase-catalyzed cellulose acetylation in aqueous and organic media.
AB  - Screening for lipases capable of catalyzing acetylation of cellulosic substrates
      was conducted in aqueous buffer solution using water-soluble carboxymethyl
      cellulose (CMC) as substrate. Lipase A12 from Aspergillus niger (A. niger) showed
      the most promising acetylation activity among 11 tested commercial microbial
      lipases and was further applied to catalyzing acetylation of solid cellulose in
      aqueous solution. This reaction was shown to be feasible with an acetylation
      extent of 0.16 wt % achieved compared with no detectable acetylation in the
      absence of enzyme. Pretreatments on cellulose substrate by ultrasonic irradiation
      and surfactant solution only slightly improved the acetylation extent by 44 and
      27%, respectively. Alternatively, this lipase-catalyzed acetylation was
      remarkably improved with solubilized cellulose as substrate in the dimethyl
      sulfoxide/paraformaldehyde solvent system, with an acetylation extent (7.87 wt %)
      nearly 50 times higher than that achieved in aqueous solution. This improvement
      was attributed to (1) the absence of bulk water and the increase in substrate
      solubility by the transition of reaction media from aqueous solution to organic
      solvents and (2) the ability of lipase A12 to remain catalytically active in
      highly polar DMSO. This discovery that the A. niger lipase was capable of
      surviving its contact with polar solvents was further confirmed by its
      considerably preserved catalytic activity on CMC acetylation in aqueous media
      after enzyme pretreatments with organic solvents of various polarities and in
      mixture media with the aqueous phase partially replaced by organic solvents.

PMID- 14656140
TI  - Highly efficient conversion of lactate to pyruvate using whole cells of
      Acinetobacter sp.
AB  - On an industrial scale, the production of pyruvate at a high concentration from
      the cheaper lactate substrate is a valuable process. To produce pyruvate from
      lactate by whole cells, various lactate-utilizing microorganisms were isolated
      from soil samples. Among them, strain WLIS, identified as Acinetobacter sp., was
      screened as a pyruvate producer. For the pyruvate preparation from lactate, the
      preparative conditions were optimized with whole cells of the strain. The cells
      cultivated in the medium containing 100 mM of l-lactate showed the highest
      biotransformation efficiency from lactate to pyruvate. The optimized dry-cell
      concentration, pH, and temperature of reaction were 6 g/L, pH 7.0-7.5, and 30
      degrees C, respectively. The influences of ethylenediaminetetraacetic acid (EDTA)
      and aeration on a biotransformation reaction were carried out under the test
      conditions. Under the optimized reaction conditions, l-lactate at concentrations
      of 200 and 500 mM were almost totally stoichiometrically converted into pyruvate
      in 8 and 12 h, respectively. About 60% of 800 mM of l-lactate was transformed
      into pyruvate in 24 h. This reduced conversion rate is probably due to the high
      substrate inhibition in biotransformation.

PMID- 14656141
TI  - Reduced formation of byproduct component C in acarbose fermentation by
      Actinoplanes sp. CKD485-16.
AB  - Acarbose fermentation was conducted by cultivation of Actinoplanes sp. CKD485-16.
      Approximately 2,300 mg/L of acarbose was produced at the end of cultivation along
      with 600 mg/L of the acarbose byproduct component C. Maltose, a known moiety of
      acarbose, should be maintained at high concentration levels in culture broths for
      efficient acarbose production. The acarbose yield increased with an increasing
      osmolality of the culture medium, with a maximum value of 3,200 mg/L obtained at
      500 mOsm/kg. Component C was also produced in proportion to the osmolality.
      Conversion of acarbose to component C was accomplished with resting whole cells.
      Inhibitors of the conversion of acarbose to component C were sought since
      component C is probably derived from acarbose. Valienamine was found to be a
      potent inhibitor, resulting in a more than 90% reduction in component C formation
      at a 10 microM concentration. Effects were similar in a 1,500-L pilot fermentor
      with acarbose and component C yields of 3,490 and 43 mg/L at 500 mOsm/kg,
      respectively.

PMID- 14656142
TI  - An optimized method for Aspergillus niger spore production on natural carrier
      substrates.
AB  - Aspergillus niger spores have wide ranging applications in the fermentation
      industry as well as in wastewater treatment. We present an optimized method for
      production of A. niger spores on natural substrates such as rice, split pea, and
      millet. The specific productivity (number of spores per gram of dry substrate)
      was 31-fold greater and volumetric productivity was 750-fold greater compared to
      agar slopes. The important process variables were incubation temperature,
      moisture content, and inoculum quantity. We find that the optimal condition for
      total spore count is different from the viable spore count for millet. The
      optimum lies in a narrow region defined by the process parameters. Of the three
      substrates tested split pea gave the highest specific spore productivity of 3.1 x
      10(10) spores per gram of dry substrate. This is the first report of systematic
      study on the effect of process parameters on spore viability. The method of A.
      niger spore production on natural substrate appears advantageous as compared to
      the currently practiced method in terms of scale-up, cost, and ease of operation.

PMID- 14656143
TI  - Macro-level and genetic-level responses of Bacillus subtilis to shear stress.
AB  - Responses of bacterial (Bacillus subtilis) cells under different shear levels,
      from both the macro and genetic viewpoints, have been presented. The responses
      were studied using a novel, couette flow bioreactor (CFB), in which the entire
      cultivation can be performed under defined shear conditions. Oxygen supply, the
      normal limiting factor for entire cultivations under defined shear conditions,
      has been achieved by passing air through a poly(tetrafluoroethylene) (PTFE)
      membrane fixed on the inner cylinder of the CFB. More importantly, analyses of
      the oxygen transfer capabilities as well as the shear rates show that in this
      CFB, the effects of defined shear can be studied without interference from the
      effects of oxygen supply. Further, the shake flask can be used as a proper
      control for studying the shear effects, mainly because the shear rate in the
      shake flask under normal shaker operating conditions of 190 rpm has been
      estimated to be a negligible 0.028 s(-1) compared to a value of 445 s(-1) at the
      lowest rpm employed in the CFB. At the macro level the cell size decreased by
      almost 50% at 1482 s(-1) compared to that at 0.028 s(-1), the growth rate
      increased by 245%, and the maximum cell concentration increased by 190% when the
      shear rate was increased from 0.028 to 1482 s(-1). The specific intracellular
      catalase level increased by 335% and protease by 87% at 1482 s(-1) as compared to
      the control cultures at a shear rate 0.028 s(-1). In addition, the specific
      intracellular reactive oxygen species level (siROS) at the highest shear rate was
      9.3-fold compared to the control conditions. At the genetic level we have
      established the involvement of the transcription factor, sigma(B), in the
      bacterial responses to shear stress, which was unknown in the literature thus
      far; the sigma(B) expression correlated inversely with the siROS. Further,
      through experiments with ROS quenchers, we showed that ROS regulated sigma(B)
      expression under shear.

PMID- 14656144
TI  - Optimization of cyclodextrin glycosyltransferase production from Klebsiella
      pneumoniae AS-22 in batch, fed-batch, and continuous cultures.
AB  - Production of a novel cyclodextrin glycosyltransferase (CGTase) from Klebsiella
      pneumoniae AS-22 strain, which converts starch predominantly to alpha-CD at high
      conversion yields, in batch, fed-batch, and continuous cultures, is presented. In
      batch fermentations, optimization of different operating parameters such as
      temperature, pH, agitation speed, and carbon-source concentration resulted in
      more than 6-fold increase in CGTase activity. The enzyme production was further
      improved by two fed-batch approaches. First, using glucose-based feed to increase
      cell density, followed by starch-based feed to induce enzyme production, resulted
      in high cell density of 76 g dry cell weight/L, although the CGTase production
      was low. Using the second approach of a single dextrin-based feed, 20-fold higher
      CGTase was produced compared to that in batch fermentations with media containing
      tapioca starch. In continuous operation, more than 8-fold increase in volumetric
      CGTase productivity was obtained using dextrin-based media compared to that in
      batch culture using starch-based media.

PMID- 14656145
TI  - Development of a segmented model for a continuous electrophoretic moving bed
      enantiomer separation.
AB  - With the recent demonstration of a continuous electrophoretic "moving bed"
      enantiomer separation at mg/h throughputs, interest has now turned to scaling up
      the process for use as a benchtop pharmaceutical production tool. To scale the
      method, a steady-state mathematical model was developed that predicts the process
      response to changes in input feed rate and counterflow or "moving bed"
      velocities. The vortex-stabilized apparatus used for the separation was modeled
      using four regions based on the different hydrodynamic flows in each section.
      Concentration profiles were then derived on the basis of the properties of the
      Piperoxan-sulfated beta-cyclodextrin system being studied. The effects of
      different regional flow rates on the concentration profiles were evaluated and
      used to predict the maximum processing rate and the hydrodynamic profiles
      required for a separation. Although the model was able to qualitatively predict
      the shapes of the concentration profiles and show where the theoretical limits of
      operation existed, it was not able to quantitatively match the data from actual
      enantiomer separations to better than 50% accuracy. This is believed to be due to
      the simplifying assumptions involved, namely, the neglect of electric field
      variations and the lack of a competitive binding isotherm in the analysis.
      Although the model cannot accurately predict concentrations from a separation, it
      provides a good theoretical framework for analyzing how the process responds to
      changes in counterflow rate, feed rate, and the properties of the molecules being
      separated.

PMID- 14656146
TI  - Purification and concentration of alkaline phosphatase by selective
      permeabilization of Escherichia coli using reverse micellar solutions.
AB  - Recovery of alkaline phosphatase (AP) from the periplasm of Escherichia coli
      using reverse micellar solutions (RMSs) of sodium dioctyl sulfosuccinate (AOT) in
      aliphatic hydrocarbons has been attempted. A variety of surface-active agents,
      solvents, and reverse micellar conditions were screened, and an excellent
      recovery of the enzyme in a concentrated form, with a high purification factor,
      was obtained in a single-step process. The permeabilization process strongly
      depended on the water content of the RMS as well as on the amount of water
      coating the microbial cell surface. The product was almost free from nucleic
      acids. In addition, because of the low affinity of AOT and the organic solvent
      for the aqueous phase, contamination by the permeabilizing agents would also be
      negligible.

PMID- 14656147
TI  - Application of magnetic agarose support in liquid magnetically stabilized
      fluidized bed for protein adsorption.
AB  - A novel magnetic agarose support (MAS) was fabricated for application in a liquid
      magnetically stabilized fluidized bed (MSFB). It was produced by water-in-oil
      emulsification method using a mixture of agarose solution and nanometer-sized
      superparamagnetic Fe(3)O(4) particles as the aqueous phase. The MAS showed good
      superparamagnetic responsiveness in a magnetic field. A reactive triazine dye,
      Cibacron blue 3GA (CB), was coupled to the gel to prepare a CB-modified magnetic
      agarose support (CB-MAS) for protein adsorption. Lysozyme was used as a model
      protein to test the adsorption equilibrium and kinetic behavior of the CB-MAS.
      The dependence of bed expansion in the MSFB with a transverse magnetic field on
      liquid velocity and magnetic field intensity was investigated. Liquid-phase
      dispersion behavior in the MSFB was examined by measurements of residence time
      distributions and compared with that obtained in packed and expanded beds.
      Dynamic lysozyme adsorption in the MSFB was also compared with those in packed
      and expanded beds. The dynamic binding capacity at 10% breakthrough was estimated
      at 55.8 mg/mL in the MSFB, higher than that in the expanded bed (31.1 mg/mL) at a
      liquid velocity of 45 cm/h. The results indicate that the CB-MAS is promising for
      use in liquid MSFB for protein adsorption.

PMID- 14656148
TI  - Mechanisms controlling the temperature-dependent binding of proteins to poly(N
      isopropylacrylamide) microgels.
AB  - Poly(N-isopropylacrylamide) (PNIPA) microgels may offer several advantages over
      PNIPA-modified surfaces when used as sorbents in temperature-sensitive
      chromatography. Yet, a full exploitation of these advantages requires a better
      understanding of the mechanisms controlling the separation process. As a model
      system, we have studied the binding of three proteins (bovine serum albumin
      (BSA), ovalbumin, and lysozyme) to PNIPA microgels. Binding experiments were
      conducted both below (25 degrees C) and above (37 degrees C) the volume phase
      transition temperature of the gel, T(c). The analysis of the binding isotherms
      has shown that although an average gel particle contained a larger amount of
      protein below the phase transition temperature, the concentration of the protein
      within the particle was higher above this temperature. These findings were
      attributed to changes in the binding loci due to temperature swings around T(c):
      whereas a sorption mechanism is dominant below this temperature, surface
      adsorption was more important above it. A comparison between the three studied
      proteins has shown that below T(c) the binding increases with a decrease in the
      molecular weight. On the other hand, no significant difference in the bound
      protein amounts was observed above the phase transition temperature. Our results
      imply that, despite the increase in the gel's hydrophobicity above the phase
      transition temperature, the resolution in bioseparations based on PNIPA gels is
      not necessarily better above T(c).

PMID- 14656149
TI  - Proteome analysis of antibody-expressing CHO cells in response to hyperosmotic
      pressure.
AB  - To better understand intracellular responses to hyperosmotic pressure of
      recombinant Chinese hamster ovary (rCHO) cells expressing an antibody, we have
      taken a proteomics approach. Using two-dimensional electrophoresis and mass
      spectrometry, a proteome profile of rCHO cells comprising 23 identified proteins
      was established. On the basis of this proteome profile, we found three proteins
      of which expression levels were significantly changed at 450 mOsm/kg. Compared to
      the results at 300 mOsm/kg, two glycolytic enzymes, glyceraldehyde-3-phosphate
      dehydrogenase and pyruvate kinase, were found to be up-regulated, probably
      leading to an increased metabolic energy for antibody synthesis. The elevation of
      specific glucose consumption rate at 450 mOsm/kg agreed with the up-regulation of
      these glycolytic enzymes. On the other hand, tubulin expression was down
      regulated, reflecting a depressed cell growth rate at 450 mOsm/kg. Taken
      together, this study shows the potential of the proteomics approach in
      understanding intracellular and physiological changes in cells and seeking a
      better insight into possible environmental or genetic manipulation approaches for
      increasing foreign protein production in rCHO cells.

PMID- 14656150
TI  - Monte Carlo simulation of LNCaP human prostate cancer cell aggregation in liquid
      overlay culture.
AB  - Neoplastic cells self-assemble in liquid-overlay cultures into multicellular
      spheroids that resemble micrometastases and avascular regions of larger tumors. A
      Monte Carlo simulation based on Meakin's cluster-cluster aggregation model
      resolved the physical mechanisms by which LNCaP human prostate cancer cells
      aggregate in this environment. The best-fit solution suggests that LNCaP cells
      aggregate with an adhesion probability of 0.5% when they migrate within a radius
      of influence between cell centers of 180 microm, 10 times the cell diameter. The
      sweeping radius of influence is indicative of cell tethering and/or chemotaxis
      and results in an intrinsic rate of self-aggregation that increases from k(11) =
      1.5 h(-1) for single cells to k(1010) = 17.5 h(-1) for 10-mers. Similar rates are
      predicted by Smoluchowski's collision theory (1), suggesting that they are
      inherent properties of LNCaP liquid-overlay culture. Aggregates form more compact
      structures in culture than during simulation as measured by the fractal
      dimension: D(F) = 1.74 +/- 0.04 for 10-mers in culture vs D(F) = 1.25 +/- 0.10
      for simulated 10-mers. Additional restructuring would further extend the radius
      of influence and diminish adhesion. Applications of this work include the
      production of highly viable spheroids for drug testing and basic oncological
      research.

PMID- 14656151
TI  - Retroviral delivery of the ecdysone-regulatable gene expression system.
AB  - We describe a set of Moloney Murine Leukemia Virus (MoMLV)-based replication
      defective retroviral vectors for delivery of the ecdysone-inducible system into
      mammalian cells. The vector pFB-ERV contains a tricistronic CMV expression
      cassette from which the ecdysone receptor proteins RXR and VgEcR are expressed,
      with the neo-resistance marker expressed as the third open reading frame (ORF).
      The inducible vector pCFB-EGSH contains an ecdysone-inducible expression cassette
      inserted between the viral LTRs in the antisense orientation relative to that for
      the viral promoter. Potential interference from the proviral 5' LTR is obviated
      due to a SIN deletion in the 3' LTR. When used together, induction ratios of over
      1000-fold were achieved in NIH3T3 cells using firefly luciferase as a reporter.

PMID- 14656152
TI  - Electrophysiological and morphological characterization of rat embryonic
      motoneurons in a defined system.
AB  - In an attempt to integrate biological components with silicon-based devices and
      systems, artificial silane surfaces have been successfully used to grow
      motoneurons in a defined environment. In this study we characterized the
      morphology and electrophysiology of purified rat embryonic (E14) motoneurons
      grown on a self-assembled monolayer (SAM) of N-1[3
      (trimethoxysilyl)propyl]diethylenetriamine (DETA) versus that on
      ornithine/laminin surfaces in serum-free media. On DETA motoneurons were flat and
      grew more processes, whereas on ornithine/laminin they tended to aggregate. The
      membrane time constant, a characteristic associated with electrotonic
      compactness, was significantly longer for motoneurons grown on DETA. Other
      electrophysiological parameters were similar for the motoneurons on the different
      surfaces. This is the first study where purified ventral horn motoneurons were
      cultured in a completely defined (nonbiological surface, serum-free) environment.

PMID- 14656153
TI  - Optimal NS0 cell growth in a hollow fiber bioreactor requires increased serum
      concentration or a cholesterol supplement on the cell side of the fiber.
AB  - An NSO/GS cell line secreting a humanized antibody was routinely propagated in a
      T-flask using 2% serum. For scale-up of antibody production, this cell line was
      inoculated into a hollow fiber system using the same serum concentration. The
      metabolic activity increased for a few days in the hollow fiber system, but
      invariably the activity dropped dramatically as the cells died by day 7. A hollow
      fiber micro-bioreactor was used as a screening tool to examine possible reasons
      for cell death in the large-scale system. As seen in the hollow fiber system,
      cells died when 2% serum was used either on the cell side only or on both sides
      of the fiber in the micro-bioreactor. In contrast, the use of 20% serum on the
      cell side of the fiber and basal medium on the non-cell side resulted in good
      cell expansion at high viability. Regardless of the cell side serum
      concentration, no further growth enhancements were seen when up to 20% serum was
      placed on the non-cell side of the fiber. These results suggest that a serum
      component that does not readily cross the fiber is limiting cell growth in the
      hollow fiber bioreactors. The addition of a cholesterol-rich lipid supplement
      resulted in better cell growth in the micro-bioreactor, while the addition of
      other non-cholesterol lipid supplements resulted in no growth enhancement. The
      growth-enhancing properties of the cholesterol supplement were more pronounced at
      lower serum concentrations, suggesting that poor growth at low serum
      concentration was due to suboptimal cholesterol levels. When the cell side serum
      concentration was increased to 20% in the hollow fiber system, cells grew and
      filled the bioreactor, allowing a 39-day production run. These results
      demonstrate that this NSO cell line requires an increased cell side serum
      concentration for optimal growth and that this requirement is likely due to the
      inherent cholesterol dependency of this cell line.

PMID- 14656154
TI  - Using PC12 cells to evaluate poly(caprolactone) and collagenous microcarriers for
      applications in nerve guide fabrication.
AB  - Tissue-engineered nerve guides can provide mechanical support as well as chemical
      stimulation for nerve regeneration. PC12 cells were used to test the novel
      combination of poly(caprolactone) (PCL) and macroporous collagen-based
      microcarriers (CultiSphers) as an initial phase in the fabrication of
      multichanneled nerve guides. Laminin-coated PCL was an effective matrix for the
      attachment, proliferation, and viability of PC12 cells, relative to uncoated PCL.
      PC12 cells attached to laminin-coated PCL and extended neurites when cultured in
      the presence of nerve growth factor (NGF). PC12 cells attached and proliferated
      on CultiSphers and extended neurites in response to NGF. A novel PCL/CultiSpher
      composite material also supported PC12 attachment and proliferation and provides
      a potentially useful material for the fabrication of synthetic nerve guides.

PMID- 14656155
TI  - Generation of a telomere-based episomal vector.
AB  - We have developed a telomere-based episome by large-scale amplification in
      Escherichia coli cells. This episome consists of a PAC vector in which a 6 Kb
      sequence, containing an array of telomeric repeats spaced by a synthetic
      sequence, is tandemly repeated by large-scale multimerization in E. coli. After
      transfection in human HT1080 cells, the construct, called clone 106, was able to
      persist in episomal form or integrated into some endogenous chromosomes.
      Integrations occurred exclusively at the telomeres. Episomes were still present
      in HT1080 cells after more than 100 days in the absence of selection.
      Integrations of clone 106 into the telomeric regions were retained only under
      selective conditions, and when the selection was removed the construct was
      progressively eliminated from the chromosome. The long-term maintenance of clone
      106 into human cells as an episome and its ability to integrate transiently into
      the telomeres of the host chromosomes suggest that this PAC-based episome is
      potentially a good candidate vector for gene therapy applications.

PMID- 14656156
TI  - Effects of epidermal growth factor on fibroblast migration through biomimetic
      hydrogels.
AB  - We have previously reported on the development and use of synthetic hydrogel
      extracellular matrix (ECM) analogues that can be used to study the mechanisms of
      migration. These biomimetic hydrogels consist of bioinert poly(ethylene glycol)
      diacrylate derivatives with proteolytically degradable peptide sequences included
      in the backbone of the polymer and adhesion peptide sequences grafted into the
      network. Cells adhere to the hydrogel via interaction between the grafted
      adhesion ligands and receptors on the cell surface. The cells migrate through the
      three-dimensional system by secreting the appropriate proteolytic enzymes, which
      are involved in cell migration and are targeted to the peptide sequences
      incorporated in the backbone of the polymer. It was observed that cell migration
      has a biphasic dependence on adhesion ligand concentration, with optimal
      migration at intermediate ligand levels. In this study, we demonstrate that we
      can covalently attach epidermal growth factor (EGF) to PEG and graft them into
      the hydrogels. It was observed that EGF when tethered maintained mitogenic
      activity. It was also observed that fibroblast migration significantly increased
      in the presence of the grafted EGF through the collagenase-sensitive hydrogels.
      In addition, the increase in migration was found to be independent from the
      proliferative response of the cells. These synthetic ECM analogues allow one to
      systematically control identities and concentrations of biomolecules and are
      useful tools to study mechanisms of cell migration.

PMID- 14656157
TI  - Field-flow fractionation as analytical technique for the characterization of dry
      yeast: correlation with wine fermentation activity.
AB  - Important oenological properties of wine depend on the winemaking yeast used in
      the fermentation process. There is considerable controversy about the quality of
      yeast, and a simple and cheap analytical methodology for quality control of yeast
      is needed. Gravitational field flow fractionation (GFFF) was used to characterize
      several commercial active dry wine yeasts from Saccharomyces cerevisiae and
      Saccharomyces bayanus and to assess the quality of the raw material before use.
      Laboratory-scale fermentations were performed using two different S. cerevisiae
      strains as inocula, and GFFF was used to follow the behavior of yeast cells
      during alcoholic fermentation. The viable/nonviable cell ratio was obtained by
      flow cytometry (FC) using propidium iodide as fluorescent dye. In each
      experiment, the amount of dry wine yeast to be used was calculated in order to
      provide the same quantity of viable cells. Kinetic studies of the fermentation
      process were performed controlling the density of the must, from 1.071 to 0.989
      (20/20 density), and the total residual sugars, from 170 to 3 g/L. During the
      wine fermentation process, differences in the peak profiles obtained by GFFF
      between the two types of commercial yeasts that can be related with the unlike
      cell growth were observed. Moreover, the strains showed different fermentation
      kinetic profiles that could be correlated with the corresponding fractograms
      monitored by GFFF. These results allow optimism that sedimentation FFF techniques
      could be successfully used for quality assessment of the raw material and to
      predict yeast behavior during yeast-based bioprocesses such as wine production.

PMID- 14656158
TI  - A new HPLC-ELSD method to quantify indican in Polygonum tinctorium L. and to
      evaluate beta-glucosidase hydrolysis of indican for indigo production.
AB  - A method to quantify the indigo precursor indican (indoxyl-beta-D-glucoside) in
      Polygonum tinctorium L. has been developed. Plant material was extracted in
      deionized water, and indican was identified and quantified using high performance
      liquid chromatography (HPLC) coupled to an evaporative light scattering detector
      (ELSD). Results confirmed that with this method it is possible to measure indican
      content in a short time, obtaining reliable and reproducible data. Using this
      method, leaf indican content was quantified every 15 days during the growing
      season (from May to October) in P. tinctorium crops grown in a field experiment
      in Central Italy. Results showed that indican increased along the growing season
      until flowering and was positively affected by photosynthetic active radiation
      (PAR). Indican is naturally hydrolyzed by native beta-glucosidase to indoxyl and
      glucose, the indoxyl yielding indigo. The activity of two enzymes, sweet almond
      beta-glucosidase and Novarom G preparation, were compared with P. tinctorium
      native beta-glucosidase to evaluate indigo production. Results showed that the
      ability to promote indigo formation increased as follows: almond beta-glucosidase
      <or= Novarom G.

PMID- 14656159
TI  - Determination of size distribution and encapsulation efficiency of liposome
      encapsulated hemoglobin blood substitutes using asymmetric flow field-flow
      fractionation coupled with multi-angle static light scattering.
AB  - In this study, we investigated the size distribution, encapsulation efficiency,
      and oxygen affinity of liposome-encapsulated tetrameric hemoglobin (LEHb)
      dispersions and correlated the data with the variation in extruder membrane pore
      size, ionic strength of the extrusion buffer, and hemoglobin (Hb) concentration.
      Asymmetric flow field-flow fractionation (AFFF) in series with multi-angle static
      light scattering (MASLS) was used to study the LEHb size distribution. We also
      introduced a novel method to measure the encapsulation efficiency using a
      differential interferometric refractive index (DIR) detector coupled to the AFFF
      MASLS system. This technique was nondestructive toward the sample and easy to
      implement. LEHbs were prepared by extrusion using a lipid combination of
      dimyristoyl-phosphatidylcholine, cholesterol, and dimyristoyl
      phosphatidylglycerol in a 10:9:1 molar ratio. Five initial Hb concentrations (50,
      100, 150, 200, and 300 mg Hb per mL of buffer) extruded through five different
      membrane pore diameters (400, 200, 100, 80, and 50 nm) were studied. Phosphate
      buffered saline (PBS) and phosphate buffer (PB) both at pH 7.3 were used as
      extrusion buffers. Despite the variation, extrusion through 400-nm pore diameter
      membranes produced LEHbs smaller than the pore size, extrusion through 200-nm
      membranes produced LEHbs with diameters close to the pore diameter, and extrusion
      through 100-, 80-, and 50-nm membranes produced LEHbs larger than the pore sizes.
      We found that the choice of extrusion buffer had the greatest effect on the LEHb
      size distribution compared to either Hb concentration or extruder membrane pore
      size. Extrusion in PBS produced larger LEHbs and more monodisperse LEHb
      dispersions. However, LEHbs extruded in PB generally had higher Hb encapsulation
      efficiencies and lower methemoglobin (metHb) levels. The choice of extrusion
      buffer also affected how the encapsulation efficiency correlated with Hb
      concentration, extruder pore size, and the metHb level. The most optimum
      encapsulation efficiency and amount of Hb entrapped were achieved at the highest
      Hb concentration and the largest pore size for both extrusion buffers (62.38% and
      187.14 mg Hb/mL of LEHb dispersion extruded in PBS, and 69.98% and 209.94 mg
      Hb/mL of LEHb dispersion extruded in PB). All LEHbs displayed good oxygen
      carrying properties as indicated by their P(50) and cooperativity coefficients.
      LEHbs extruded in PB had an average P(50) of 23.04 mmHg and an average Hill
      number of 2.29, and those extruded in PBS had average values of 27.25 mmHg and
      2.49. These oxygen-binding properties indicate that LEHbs possess strong
      potential as artificial blood substitutes. In addition, the metHb levels in PB
      LEHb dispersions are significantly low even in the absence of antioxidants such
      as N-acetyl-L-cysteine.

PMID- 14656160
TI  - Detection of benzene, toluene, ethyl benzene, and xylenes (BTEX) using toluene
      dioxygenase-peroxidase coupling reactions.
AB  - We have developed a simple, whole-cell bioassay for the detection of bioavailable
      benzene, toluene, ethyl benzene, and xylenes (BTEX) and similar compounds. A
      genetically engineered E. coli strain expressing toluene dioxygenase (TDO) and
      toluene dihydrodiol dehydrogenase (TodD) was constructed, enabling the conversion
      of BTEX into their respective catechols, which were quickly converted into
      colored products by a horseradish peroxidase (HRP)-coupled reaction. The
      intensity of the color formation was correlated to concentrations of the BTEX
      compounds. Under the optimized conditions, a detection limit (defined as three
      times the standard deviation of the response obtained from the blank) of 10, 10,
      20, and 50 microM was observed for benzene, toluene, ethyl benzene, and xylene,
      respectively. The bioassay was selective toward BTEX-related compounds with no
      interference observed with commonly used pesticides, herbicides, and organic
      solvent. The bioassay was very stable with little change in response over a 10
      week period. The excellent stability suggests that the reported bioassay may be
      suitable for field monitoring of BTEX to identify and track contaminated water
      and follow the bioremediation progress.

PMID- 14656161
TI  - Assessment of in-line near-infrared spectroscopy for continuous monitoring of
      fermentation processes.
AB  - The application of NIR in-line to monitor and control fermentation processes was
      investigated. Determination of biomass, glucose, and lactic and acetic acids
      during fermentations of Staphylococcus xylosus ES13 was performed by an
      interactance fiber optic probe immersed into the culture broth and connected to a
      NIR instrument. Partial least squares regression (PLSR) calibration models of
      second derivative NIR spectra in the 700-1800 nm region gave satisfactory
      predictive models for all parameters of interest: biomass, glucose, and lactic
      and acetic acids. Batch, repeated batch, and continuous fermentations were
      monitored and automatically controlled by interfacing the NIR to the bioreactor
      control unit. The high frequency of data collection permitted an accurate study
      of the kinetics, supplying lots of data that describe the cultural broth
      composition and strengthen statistical analysis. Comparison of spectra collected
      throughout fermentation runs of S. xylosus ES13, Lactobacillus fermentum ES15,
      and Streptococcus thermophylus ES17 demonstrated the successful extension of a
      unique calibration model, developed for S. xylosus ES13, to other strains that
      were differently shaped but growing in the same medium and fermentation
      conditions. NIR in-line was so versatile as to measure several biochemical
      parameters of different bacteria by means of slightly adapted models, avoiding a
      separate calibration for each strain.

PMID- 14656162
TI  - Oxidation-reduction potential as a control variable for the anaerobic stage
      during anaerobic-aerobic p-nitrophenol degradation.
AB  - Combined anaerobic-aerobic processes are a viable alternative for the treatment
      of xenobiotic compounds that are difficult to treat by traditional processes. The
      variable nature of the sequencing batch reactors, SBR, systems allows
      manipulation of the selective pressure on the microorganisms. Then, the activity
      of the community can be dynamically adjusted to meet changing effluents
      conditions. To improve the response of the SBR to changing influent conditions,
      several efforts have been made to automate and control the duration of the
      sequential phases of the SBR. The objective of this work is to present and
      discuss the feasibility of the use of the oxidation-reduction potential, ORP, as
      a control variable for the determination of the anaerobic phase length in an
      anaerobic-aerobic SBR used to degrade p-nitrophenol, PNP. The control of the
      anaerobic phase of the anaerobic-aerobic reactor was achieved with software
      developed at the Institute of Engineering-UNAM. During the anaerobic stage, the
      PNP is reduced to p-aminophenol, PAP. As a consequence of the compound
      transformation, there is a change in the oxidation-reduction potential of the
      culture medium. This change was used to indicate the minimal concentration of PNP
      and, as a consequence, the maximal PAP concentration. The feasibility of the
      algorithm for using the variations in the ORP to determine on-line the length of
      the anaerobic stage in an anaerobic-aerobic process was demonstrated in our
      laboratory.

PMID- 14656163
TI  - Neural-network-based identification of tissue-type plasminogen activator protein
      production and glycosylation in CHO cell culture under shear environment.
AB  - An artificial neural network (ANN) modeling scheme has been constructed for the
      identification of both recombinant tissue-type plasminogen activator (r-tPA)
      protein production and glycosylation from Chinese hamster ovary (CHO) cell
      culture, cultivated in a stirred bioreactor. A series of hybrid feed-forward
      backpropagation neural networks were constructed to function as a software
      sensor. This enabled predictions of viable cell density, r-tPA content, and r-tPA
      glycosylation. The sensor was based on an initial input vector space consisting
      of simple metabolite concentrations, batch cultivation time, and a description of
      shear stress applied to the culture. Metabolite concentrations of the culture
      supernatant, included in the input vector space, were obtained from a single
      isocratic HPLC measurement. The shear stress component of the input space enabled
      accurate culture state prediction over a wide range of agitation rates.
      Coefficient of determination (r(2)) values between ANN predicted and experimental
      measurements of 0.945, 0.943, 0.956, and 0.990 were calculated to validate
      individual ANN prediction accuracy for total ammonia, apparent viable cell
      density, total r-tPA, and Type II glycoform concentrations, respectively.

PMID- 14656164
TI  - Evaluation of ion exchange resins for removal of inhibitory compounds from corn
      stover hydrolyzate for xylitol fermentation.
AB  - The use of dilute acids to catalyze the hydrolysis of hemicellulose to its sugar
      constituents is well-known and effective. However, a major problem associated
      with this pretreatment is the poor fermentability of the produced hydrolyzate as
      a result of the presence of the microorganism's inhibitory compounds. In the
      present work, seven ion-exchange resins were tested in order to detoxify corn
      stover hydrolyzate. Regarding xylose recovery, it was observed that more than 92%
      recovery was feasible. Furfural removal varied from 53.% to 99.%, and
      hydroxymethylfurfural (HMF) removal was effective between 37% and 100%. Acetic
      acid was totally removed by Purolite A 103 S resin. Corn stover hydrolyzate (CSH)
      treated with Purolite A 103 S, and Finex CS 14 GC resins, was tested as substrate
      for xylitol production using a yeast, Candida mogii. Product yields, Yp/s, of
      0.41 and 0.37 g/g and cellular yields, Yx/s, of 0.24 and 0.13 g/g, respectively,
      were obtained using the two types of resin-treated hydrolyzates.

PMID- 14656165
TI  - Scale-up of a liquid static culture process for hyperproduction of ganoderic acid
      by the medicinal mushroom Ganoderma lucidum.
AB  - Scale-up of a liquid static culture process was studied for hyperproduction of
      ganoderic acid (GA) by a famous Chinese traditional medicinal mushroom, Ganoderma
      lucidum. Initial volumetric oxygen transfer coefficient (K(L)a) and area of
      liquid surface per liquid volume (A(s)) were identified as key factors affecting
      cell growth and GA accumulation in liquid static cultures of G. lucidum, on the
      basis of which a multilayer static bioreactor was designed. At a low initial
      K(L)a level of 2.1 h(-1), a thick layer of white mycelia was formed on the liquid
      surface, and an optimal production of total GA (i.e., GA production in the liquid
      and on the liquid surface) was obtained. Both the formation of white mycelia and
      production of GA on the liquid surface were enhanced with an increase of A(s)
      within the range as investigated (0.24-1.53 cm(2)/mL). At an A(s) value of 0.90
      cm(2)/mL, the total GA production reached maximum. A successful scale-up from a
      20-mL static T-flask to a 7.5-L three-layer static bioreactor was achieved based
      on initial K(L)a. The maximum biomass (20.8 +/- 0.1 g DW/L), GA content (4.96 +/-
      0.13 mg/100 mg DW), and total GA production (976 +/- 35 mg/L) were attained in
      static bioreactors. Not only GA content but also its production obtained in this
      work were the highest ever reported.

PMID- 14656166
TI  - Acute superior mesenteric artery embolism: rapid reperfusion with hydrodynamic
      thrombectomy and pharmacological thrombolysis.
AB  - PURPOSE: To report a case of acute superior mesenteric artery (SMA) embolism
      successfully treated with hydrodynamic thrombectomy and pharmacological
      thrombolysis. CASE REPORT: A 67-year-old man was admitted to the hospital with
      acute severe abdominal pain. Selective angiography via a femoral puncture
      revealed a complete embolic occlusion distal to the first jejunal branch of the
      SMA. Hydrodynamic thrombectomy resolved the severe abdominal pain of the patient
      in approximately 10 minutes after the start of thrombectomy. Local continuous
      thrombolysis with urokinase resulted in near complete restoration of the
      mesenteric flow after 24 hours. The patient made an uneventful recovery and
      continues to do well on warfarin therapy 8 months after treatment; he has shown
      no evidence of malabsorption. CONCLUSIONS: Although insertion of the device into
      the SMA via a femoral puncture is a difficult approach, we propose that
      hydrodynamic thrombectomy followed by local thrombolysis is a useful treatment
      for acute superior mesenteric artery embolism.

PMID- 14656167
TI  - Technological advances in the design of catheters and devices used in renal
      artery interventions: impact on complications.
AB  - PURPOSE: To analyze the impact of technical improvements in stent devices and
      guiding catheters (e.g., reduced device diameter, increased flexibility) on the
      complication rates associated with percutaneous renal artery interventions.
      METHODS: During a 5-year period (1997-2001), 268 consecutive patients (178 men;
      mean age 67+/-9 years) had 370 atherosclerotic renal artery stenoses (RAS) > or
      =70% treated with angioplasty/stenting in 320 procedures. The guiding catheter
      technique was used routinely until 2000; in 2001, a guiding sheath was used in
      29% of cases. From 1997 to 2000, sealing devices were frequently used for sheath
      removal; during the last year, the sheaths were removed using the Femostop
      device. RESULTS: In 320 interventions, 32 (10%) complications occurred, with a
      decreasing frequency during the last 2 years (1996/97: 13% [7/53]; 1998: 16%
      [9/57]; 1999: 15% [11/74]; 2000: 4% [3/70]; 2001: 3% [2/66]). There were 21
      (6.6%) local complications, including 4 cases requiring permanent hemodialysis
      after the intervention and 11 (3.4%) access site complications. No procedure
      related death occurred. During the study period, the average sheath diameter was
      reduced from 8.15+/-0.76 F to 6.15+/-0.63 F (p<0.05). Mean procedural time was
      reduced from 42+/-13 minutes to 23+/-11 minutes (p<0.05). The initial heparin
      dose was reduced from 10,000 to 5000 units. CONCLUSIONS: In parallel with the use
      of more flexible catheters and premounted stents of lower profile, the
      complication rate of renal angioplasty/stenting of atherosclerotic RAS has been
      reduced significantly during a 5-year period.

PMID- 14656168
TI  - Percutaneous management of extensive clot trapped in a temporary vena cava
      filter.
AB  - PURPOSE: To present percutaneous management of extensive clot trapped in a
      temporary inferior vena cava (IVC) filter. CASE REPORT: A 20-year-old man with a
      large sacral tumor and left external iliac vein thrombosis had a wire-mounted
      Gunther temporary filter (GTF) prophylactically placed in the infrarenal IVC
      prior to tumor resection. The 7-day postsurgical venogram prior to filter removal
      showed extensive clot trapped by the filter, as well as interval cephalic
      migration, with the filter tip now at the level of the renal veins. A Gunther
      Tulip MReye (GTM) filter was deployed but not released above the renal veins to
      prevent clot migration during caudal withdrawal of the wire-mounted GTF. After
      creating enough space in the infrarenal IVC, the GTM was repositioned and fully
      released with its apex now below the renal veins. The GTF was then uneventfully
      removed. There was no clinical evidence for significant pulmonary embolism 12
      months after placement. CONCLUSIONS: Cephalic migration of a clotted temporary
      IVC filter can be managed with intraprocedural protection against pulmonary
      embolism by first deploying a Gunther Tulip filter above the renal veins, with
      subsequent advancement below the renal veins before temporary filter removal.

PMID- 14656169
TI  - Clinical experience with retrievable Gunther Tulip vena cava filters.
AB  - PURPOSE: To report clinical experience with retrievable Gunther Tulip filters
      from implantation to retrieval and their status in nonretrieved situations.
      METHODS: Seventy-five Gunther Tulip filter implantations were performed in 71
      patients (43 women; mean age 55 years). Indications for filter placement were
      pulmonary embolism (PE) or iliofemoral deep vein thrombosis (DVT) in patients
      with a contraindication to anticoagulation (43, 61%) or perioperative PE
      prophylaxis (28, 39%) in patients with confirmed iliofemoral DVT. Retrieval
      procedures were planned for each patient. Patients with nonretrieved filters were
      followed with plain radiography and duplex sonography. RESULTS: Technical success
      of filter insertion was 97.3% (73/75). Eighteen (25%) patients died from
      unrelated causes prior to retrieval attempts, and 6 other patients were too
      critically ill for a retrieval procedure. Of 49 (67%) planned retrieval attempts,
      14 (19%) filters could not be removed owing to large trapped thrombi. The mean
      implantation period for the 35 (48%) retrieved filters was 8.2 days (range 1-13).
      Delivery tilt was observed in 12 (16%) filters and during retrieval attempts in 1
      more case. For 9 nonretrieved filters, tilt and migration were observed in 22% at
      a mean follow-up of 30 months, but no venous thrombosis was assessed.
      CONCLUSIONS: Our data confirm the clinical efficacy of the Gunther Tulip filter
      during implantation and the feasibility of its retrieval. Further long-term
      follow-up should be conducted on nonretrieved filters to confirm our results.

PMID- 14656170
TI  - Initial clinical experience with percutaneous atherectomy in the infragenicular
      arteries.
AB  - PURPOSE: To evaluate the efficacy and safety of a new atherectomy device for the
      treatment of infragenicular lesions in arteries with a reference diameter of at
      least 2.5 mm. METHODS: Twenty-seven below-the-knee lesions in 17 patients (12
      men; mean age 69+/-12 years) with chronic peripheral arterial occlusive disease
      were treated with directional atherectomy. The target lesion was in the popliteal
      artery (segment 3) in 2 (7%) cases, the tibioperoneal trunk in 12 (44%), the
      peroneal artery in 8 (30%), the anterior tibial artery in 2 (7%), and the
      posterior tibial artery in 3 (11%). Six (22%) of the lesions were in-stent
      stenoses. The mean diameter stenosis was 87%+/-9%, and the mean lesion length was
      34+/-24 mm. RESULTS: All but 2 (7%) of the lesions could be treated successfully
      (residual stenosis <30%) with the atherectomy catheter (93% technical success)
      using an average of 5+/-2 (range 1-10) passes of the device. Six lesions (22%)
      were treated after predilation and 21 (78%) with primary atherectomy. In 8 (30%)
      lesions, additional balloon angioplasty was performed. The 2 failures were in
      heavily calcified lesions through which the device could not pass despite
      predilation. The mean diameter stenosis after atherectomy was 14%+/-22% (range 0%
      90%); after additional balloon angioplasty, the mean residual stenoses reduced to
      12%+/-21% (range 0%-100%). One (6%) of the 2 patients who failed atherectomy
      sustained a thrombotic occlusion of the target vessel. This complication was
      treated successfully with local lysis, but the vessel reoccluded 3 days later; a
      stent was implanted. The mean ankle-brachial index increased from 0.50+/-0.27 to
      0.86+/-0.40 before discharge. CONCLUSIONS: Below-the-knee native vessel lesions
      and in-stent restenoses with a diameter of at least 2.5 mm can be treated
      successfully and safely with this new atherectomy catheter. Additional balloon
      angioplasty was necessary in only a few cases.

PMID- 14656171
TI  - Platelet adhesion to simulated stented surfaces.
AB  - PURPOSE: To determine if the protrusion of stent struts into the flow stream,
      which creates stagnation along the wall dependent on the strut spacing, has an
      effect on platelet adhesion. METHODS: Three 2-dimensional stents with different
      strut spacings were placed in a flat-plate flow chamber. Human blood was
      collected and platelets were labeled with indium 111. The blood with radioactive
      platelets was pumped through the flow chamber for 30 minutes to produce a
      pulsatile wall shear stress of 10+/-5 dynes/cm2 (mean +/- amplitude at 1 Hz). A
      gamma counter measured radioactivity along the surface and on the stents.
      Computational flow simulations provided specific data on flow separation and wall
      shear stress for each stent strut spacing tested (2.5, 4.0, and 7.0 times the
      strut height). RESULTS: The presence of any stent provoked an elevation in
      platelet adhesion within the stented region (p<0.05). The stents with larger
      strut spacing had higher platelet adhesion on the substrate in the stented region
      (1.71+/-0.63 normalized platelet deposition for the 7.0 model and 2.11+/-1.02 for
      the 4.0 model) than stents with smaller strut spacing (1.37+/-0.68 for the 2.5
      model, p<0.05). The stents themselves showed platelet adhesion levels that were 3
      to 7 times higher than the substrates, with a similar dependence on stent strut
      spacing. CONCLUSIONS: Additional knowledge of the role of mechanical factors in
      stent restenosis will aid in designing stents that minimize intimal hyperplasia
      and restenosis. The results of this study demonstrate the importance of stent
      design-mediated blood flow patterns, with smaller strut spacings minimizing
      platelet adhesion per unit strut area.

PMID- 14656172
TI  - Chronic platelet and neutrophil adhesion: a causal role for neointimal
      hyperplasia in in-stent restenosis.
AB  - PURPOSE: To investigate the relationship between platelets and neutrophils and
      the progression of neointimal hyperplasia after angioplasty versus stenting of
      porcine coronary arteries. METHODS: Balloon angioplasty or implantation of a
      balloon-expandable stent was randomly performed in the left and right coronary
      arteries of 16 Yorkshire swine; the animals were euthanized 1 hour (n=6), 24
      hours (n=4), or 1 month (n=6) after the interventions. The adhesion of chromium
      51-labeled platelets and indium 111-labeled neutrophils was quantified (per cm2),
      and histological and morphometric analyses were performed. RESULTS: The acute
      adhesion of platelets and neutrophils observed on the injured segments 1 hour
      after the interventions was similar between the treated groups. However, at 24
      hours, stenting was associated with 2-fold more platelets and 3-fold more
      neutrophils (p<0.05) than was dilation, and stented arteries remained more
      thrombogenic at 1 month (p<0.05). Neointimal formation was more intense after
      stent implantation (3.80+/-0.77 mm, p<0.05) than after dilation (0.81+/-0.21 mm),
      and it correlated positively with the adhesion of platelets (r=0.81, p<0.002) and
      neutrophils (r=0.69, p<0.01). CONCLUSIONS: These results indicate that stent
      implantation is associated with a more intense acute and chronic, low-grade
      inflammatory response than is dilation. It appears that the chronic inflammatory
      response is, at least in part, platelet- and neutrophil-driven and contributes to
      the progression of neointimal proliferation after stenting.

PMID- 14656173
TI  - Iohexol-induced neutrophil myeloperoxidase release and activation upon contact
      with vascular stent-graft material: a mechanism contributing to the
      postimplantation syndrome?
AB  - PURPOSE: To investigate whether the contrast medium iohexol alone or in
      combination with vascular stent-graft material induces neutrophil degranulation.
      METHODS: Human whole blood or isolated human neutrophils were incubated with or
      without iohexol and vascular stent-graft material. Samples were also drawn from 5
      patients undergoing diagnostic angiography using iohexol. Myeloperoxidase and
      lactoferrin concentrations were determined by enzyme immunoassays. RESULTS: Both
      in vitro and in the patients, iohexol induced neutrophil degranulation with
      considerable individual variation in dose sensitivity and timing. The in vitro
      effect was independent of the type of anticoagulant used (ethylenediamine tetra
      acetic acid, heparin, lepirudin). Experiments using isolated neutrophils showed
      that degranulation was independent of complement activation or platelet-derived
      mediators. The dose for maximal response varied from 5 to 50 mg I/mL (10.7-107.6
      mg/mL iohexol). In vitro, vascular stent-graft material alone did not induce
      neutrophil degranulation. As compared to iohexol alone, incubation with iohexol
      and vascular stent-graft material in combination substantially increased the
      release of myeloperoxidase. CONCLUSIONS: Iohexol induces neutrophil
      degranulation, which is greatly enhanced when combined with vascular stent-graft
      material. Thus, iohexol-induced neutrophil activation may contribute to an
      inflammatory response following stent-graft implantation. We speculate that
      neutrophil activation during other procedures combining catheters and iohexol
      (e.g., angiography) may induce inflammation, which might have detrimental
      effects.

PMID- 14656174
TI  - Chronic aortic dissection complicated by disseminated intravascular coagulation:
      successful treatment with endovascular stent-grafting.
AB  - PURPOSE: To report endovascular repair of a chronic aortic dissection complicated
      by disseminated intravascular coagulation (DIC). CASE REPORT: A 61-year-old man
      developed DIC associated with a chronic Stanford type B aortic dissection that
      occurred during cardiac catheterization 12 years earlier. At the current
      admission, computed tomography showed a partially thrombosed false lumen
      extending from the aortic arch to the left common iliac artery. On angiography,
      entry and re-entry tears were identified at the right subclavian and left common
      iliac arteries, respectively. After stent-graft implantation at the entry and re
      entry sites, not only was the false lumen completely thrombosed but the DIC also
      resolved. The patient is doing well with no complication at 16 months after
      treatment. CONCLUSIONS: Endovascular stent-grafting is an acceptable alternative
      to surgical repair for aortic dissection accompanied by DIC.

PMID- 14656175
TI  - Retrograde fenestration of endoluminal grafts from target vessels: feasibility,
      technique, and potential usage.
AB  - PURPOSE: To report initial experiments involving a new method for percutaneous
      intraprocedural stent-graft fenestration from the target vessel. TECHNIQUE: In
      bench and canine models, the fabric of an implanted Zenith endograft was
      punctured easily using the stiff end of a coronary 0.014-inch guidewire delivered
      through the target vessel (e.g., renal or iliac artery). A 20-G cutting needle
      was passed over the coronary wire to enlarge the puncture site, followed by a
      cutting balloon to create a fenestration that was of sufficient size to allow
      deployment of a stent. CONCLUSIONS: In vivo endograft fenestration of a Zenith
      endograft is feasible. In addition to providing a percutaneous means of
      intentionally fenestrating a stent-graft from the artery to be perfused, the
      technique has potential application as a bailout maneuver after inadvertent side
      branch occlusion. Although the time to achieve successful fenestration in the
      experimental model was long, refinement may achieve performance times adequate to
      maintain viability of the end organ.

PMID- 14656176
TI  - Development of a branched stent-graft for endovascular repair of aortic arch
      aneurysms.
AB  - PURPOSE: To develop a branched stent-graft for endovascular repair of aortic arch
      aneurysm. METHODS: Four different prototypes of a branched aortic stent-graft
      were inserted into a rubber model of the human aortic arch under fluoroscopic
      guidance. Each prototype was tested, modified, and tested again through a series
      of 4 iterations. The first 3 prototypes had multiple short side branches, as
      docking sites for extensions into the branches of the aortic arch. The last
      iteration had only 1 short branch for an extension into the distal aorta and 1
      long branch for direct perfusion of the innominate artery. RESULTS: With every re
      design, the prototype aortic stent-graft became shorter, and its insertion site
      moved to a more proximally located arch artery. Stent-graft insertion,
      orientation, and extension also became quicker and easier with each change in
      device design. However, the only system to perform reliably was the last, which
      was subsequently used to treat a large, symptomatic pseudoaneurysm of the aortic
      arch in a high-risk patient. CONCLUSIONS: None of our multibranched systems was
      simple, safe, or durable enough for insertion into the aortic arch; only an
      iteration that had a short branch for an extension into the distal aorta and a
      long branch for direct perfusion of the innominate artery could be deployed
      without difficulty or delay.

PMID- 14656177
TI  - Endoluminal repair of a thoracic arch aneurysm using a scallop-edged stent-graft.
AB  - PURPOSE: To report a new technique of endoluminal thoracic aortic arch aneurysm
      repair using a scalloped stent-graft. CASE REPORT: A 79-year-old man presented
      with a 7.5-cm thoracic aneurysm involving the inner curve of the aortic arch.
      Endoluminal repair was performed with a scalloped stent-graft that allowed
      perfusion of the brachiocephalic (innominate) artery. Preliminary extra
      anatomical left common carotid and subclavian artery bypass grafting had been
      performed to allow coverage of the origins of these vessels. CONCLUSIONS: The use
      of fenestrated endoluminal grafts in the aortic arch can be achieved safely and
      may increase the treatment options for the high-risk patient.

PMID- 14656178
TI  - Translumbar extraperitoneal decompression for abdominal compartment syndrome
      after endovascular treatment of a ruptured AAA.
AB  - PURPOSE: To report an unusual case of abdominal compartment syndrome (ACS)
      following endovascular repair of a ruptured abdominal aortic aneurysm (rAAA) that
      had been treated with a stent-graft 3 years prior. CASE REPORT: A 68-year-old man
      with a 3-year-old Vanguard bifurcated aortic stent-graft experienced sudden back
      pain and collapse. Aneurysm rupture documented by computed tomography was due to
      dislocation of the left graft limb. A Talent aortomonoiliac graft was deployed,
      followed by a femorofemoral bypass. No endoleak was evident. A few hours later,
      the patient became oliguric and hemodynamically unstable. Increased intra
      abdominal pressure (IAP) was recorded. Abdominal decompression was performed,
      removing 1500 mL of blood from the retroperitoneum through an 18-cm lumbotomy;
      the peritoneum was opened, and another 500 mL of blood was aspirated. The IAP
      fell immediately, followed by diuresis a few hours later. The patient recovered
      and was discharged after 27 days. CONCLUSIONS: Some of the perioperative
      complications seen after conventional rAAA repair are also encountered after
      endovascular treatment. ACS requires urgent decompression, and less invasive
      approaches, such as translumbar extraperitoneal decompression, may be a good
      alternative to a midline laparotomy.

PMID- 14656179
TI  - Bare-spring thoracic endografts: the balloon stops here.

PMID- 14656180
TI  - Endovascular stent-graft repair of a complicated penetrating ulcer of the
      descending thoracic aorta: a word of caution.
AB  - PURPOSE: To report a pitfall encountered during stenting of a complicated
      penetrating ulcer of the descending thoracic aorta. CASE REPORT: A 65-year-old
      man was diagnosed with a complicated penetrating ulcer of the thoracic aorta. A
      38-mm Talent endograft was implanted. On balloon dilation of the distal end of
      the endoprosthesis, the terminal bare stent became distorted and penetrated the
      aortic wall. A 42-mm endoprosthesis was immediately placed to exclude the aortic
      perforation. Control aortography demonstrated exclusion of the original proximal
      aortic ulcer and the distal iatrogenic aortic tear. CONCLUSIONS: Endoprostheses
      may present some drawbacks in terms of elasticity and adaptability to tortuous
      and angulated diseased aortas. Caution is advised in the treatment of penetrating
      aortic ulcers where the aortic wall is diffusely friable. In this condition,
      balloon dilation should be limited to the covered portion of the stent-graft to
      prevent stent distortion and erosion through the aortic wall.

PMID- 14656182
TI  - Frequency, predictive factors, and consequences of stent-graft kink following
      endovascular AAA repair.
AB  - PURPOSE: To determine from the EUROSTAR registry the incidence of stent-graft
      kink, predictive factors for kinking, and the consequences of this complication
      on graft patency and aneurysm exclusion. METHODS: From January 1994 to June 2002,
      4613 patients who underwent endovascular aneurysm repair were registered in the
      EUROSTAR registry. Presence of kink was determined according to the information
      available on the follow-up Case Record Form. The population was divided into
      those with and without stent-graft kink. Patient characteristics, morphological
      aneurysm features, team experience, type of device, period of implantation, and
      outcome were compared between the groups by univariate analysis. Significant
      factors were subsequently submitted to a multivariate Cox proportional hazard
      analysis. RESULTS: One hundred seventy (3.7%) patients were reported as having a
      kink of the stent-graft during a mean follow-up of 21 months (range 1-72).
      Gender, neck angulation, team experience, period of implantation, ASA
      classification, and device type were independent predictors of kink. The presence
      of a kink was significantly associated with type I endoleaks (proximal and
      distal), type III endoleaks (midgraft), graft stenosis, graft limb thrombosis,
      graft migration, and conversion to open repair. No relationship was found between
      a decrease in the aneurysm diameter and the occurrence of stent-graft kink.
      CONCLUSIONS: Kinks of stent-grafts were infrequent events in the intermediate
      term. Patients most at risk were women with angulated aortic necks treated by a
      minimally experienced team. Kinks are potentially damaging events because they
      may lead to delayed device-related endoleaks, graft stenosis, thrombosis, and
      conversion to open repair. They appear more closely associated to graft migration
      than to aneurysm diameter reduction.

PMID- 14656181
TI  - Endovascular graft infection: preliminary results of an international enquiry.
AB  - PURPOSE: To investigate the frequency of aortoiliac endovascular graft infections
      and seek the main factors influencing their development. METHODS: To augment
      personal experience (1 case), a questionnaire was sent to 40 international
      centers of vascular and endovascular surgery. The literature was also reviewed to
      collect data on infections developing in endovascular grafts. RESULTS: The survey
      (85% response rate) and literature review identified 62 cases of infected
      endovascular grafts (0.4% frequency of endograft infection). In 22 (35%)
      patients, the infection manifested initially with vague symptoms only, but 41
      (65%) patients eventually presented with abdominal abscess, groin fistula, and
      septic embolization. Common bacteria, such as Staphylococcus aureus, were
      identified as the cause of most infections (54.5%). The majority (49, 79%) of the
      62 patients were treated surgically; 11 (17.7%) patients received conservative
      therapy (no therapeutic data in 2 patients). Overall mortality was 27.4% (17/62),
      and operative mortality was 16.3% (8/49). Conservative treatment led to a
      mortality rate of 36.4% (4/11). The mean follow-up for all patients was 47.8
      weeks. Possible factors influencing the development of an infection were
      secondary adjunctive procedures, immunosuppression, treatment of false aneurysms,
      and infected central lines. CONCLUSIONS: Infected endovascular grafts are an
      urgent problem that has been heretofore underestimated and will probably increase
      as follow-up lengthens. New techniques should be sought to expedite the
      diagnosis, and an international registry should be set up to provide validated
      data.

PMID- 14656183
TI  - Plain radiographic surveillance of abdominal aortic stent-grafts: the
      Liverpool/Perth protocol.
AB  - PURPOSE: To present a protocol for plain radiographic surveillance of abdominal
      aortic stent-grafts that addresses the main variables in need of standardization:
      (1) patient position, (2) radiographic centering point, and (3) focus-to-film
      distance. TECHNIQUE: Our policy is to perform baseline anteroposterior and
      lateral films following endoluminal grafting and repeat the studies annually.
      These are the most important films to assess migration and component separation;
      supplementary right and left posterior oblique radiographs may help identify
      wireform fractures. It is best to perform radiography before computed tomography
      if both tests are scheduled for the same day, as excretion of intravenous
      contrast opacifies the renal collecting systems and interferes with radiographic
      analysis. CONCLUSIONS: Evaluation of the radiographs depends on the design of the
      stent-graft, so it is important to understand graft construction and the position
      of the radiopaque markers to best assess changes on follow-up films.

PMID- 14656184
TI  - Migration versus apparent migration: importance of errors due to positioning
      variation in plain radiographic follow-up of aortic stent-grafts.
AB  - PURPOSE: To demonstrate the influence of radiographic positioning on the
      assessment of stent-graft migration using plain radiographs following
      endovascular abdominal aortic aneurysm repair. METHODS: Equations were derived to
      correct for artifactual stent-graft migration introduced by geometric distortion
      due to variations in positioning between radiographs acquired at different times.
      A phantom system was used to validate the equations. RESULTS: Errors in stent
      position increase with (1) the distance of the aortic stent-graft from the
      midline and (2) differences in radiographic centering points in the craniocaudal
      direction; other variables have little effect. For typical stent positions,
      errors are small if the centering changes by <8 cm. Consistent radiographic
      positioning to within 4 cm on successive imaging studies limits errors to 1.5 mm.
      Even if artifactual migration is large, the true migration can be reliably
      calculated to within 2 mm. CONCLUSIONS: Artifactual migration due to variation in
      radiographic centering is not usually clinically significant if care is taken to
      center radiographs consistently. Radiographs in which artifactual migration may
      be important are readily identified, and mathematical correction is
      straightforward.

PMID- 14656185
TI  - Follow-up after endovascular aortic aneurysm repair: the plain radiograph has an
      essential role in surveillance.
AB  - Periodic follow-up is mandatory for patients with aortic stent-grafts. Central to
      surveillance is the establishment of a baseline against which changes can be
      detected. Computed tomography (CT) has been the benchmark of follow-up imaging
      for endografts, but comparison of serial AP and lateral plain radiographs will
      detect structural alterations that can be missed on CT scans. In this review, we
      illustrate these common endograft complications and the value of plain
      radiographs in their detection. We believe that the plain radiograph should be
      the cornerstone of aortic endograft surveillance. However, a standardized
      protocol should be used to avoid parallax and positioning errors that affect
      interpretation.

PMID- 14656186
TI  - New post-imaging software provides fast and accurate volume data from CTA
      surveillance after endovascular aneurysm repair.
AB  - PURPOSE: To quantify intra- and interobserver variabilities when measuring total
      aneurysm volume after endovascular aneurysm repair using the Vitrea 2 System and
      to compare it in terms of accuracy and processing time with the gold standard
      methods using the Easy Vision workstation. METHODS: Total aneurysm volumes from
      30 postendograft CTA datasets were randomly selected from a database consisting
      of approximately 400 CTA datasets recorded in 89 patients. The intra- and
      interobserver variabilities were measured on the Vitrea workstation by 2
      investigators. The intermodality variability was calculated for the same
      measurements using the Easy Vision workstation. The differences of each pair of
      measurements were plotted against their mean, and the repeatability coefficient
      (RC) was calculated. The mean differences were also expressed as a percentage of
      the first measurements. RESULTS: The intraobserver mean difference was 1.6 mL
      (1.4%) with an RC of 10.8 mL (10.1%) and the interobserver mean difference was 
      1.4 mL (-1.4%) with an RC of 11.7 mL (10.2%). The intermodality mean difference
      was 1.8 mL (2.0%) with an RC of 15.8 mL (11.1%). The Vitrea workstation required
      a median of 8 minutes (interquartile range 7-10) for 1 observer and 6 minutes
      (interquartile range 5-8) for the other to perform a complete volume segmentation
      of each patient dataset compared to an estimated average of 30 minutes using the
      Easy Vision workstation. CONCLUSIONS: The Vitrea workstation provides fast and
      accurate volume data from spiral CTA follow-up of endovascular aneurysm repair.
      This software may enhance the acceptability of volume surveillance in daily
      practice.

PMID- 14656187
TI  - Percutaneous management of concomitant post-traumatic high vertebrovertebral and
      caroticojugular fistulas using balloons, coils, and a covered stent.
AB  - PURPOSE: To describe the endovascular management of vertebrovertebral and
      caroticojugular fistulas in the same patient using a combination of endovascular
      techniques including covered stent placement in the high extracranial internal
      carotid artery. CASE REPORT: A 22-year-old man presented with ipsilateral
      vertebrovertebral and caroticojugular fistulas at the C1 level several weeks
      after sustaining a solitary penetrating knife injury below the right ear. The
      right vertebral artery was sacrificed after a failed endovascular attempt to
      close the vertebrovertebral fistula. The caroticojugular fistula was treated with
      a self-expanding covered stent (Wallgraft) with exclusion of the fistula and
      preservation of flow through the carotid artery. CONCLUSIONS: Preservation of the
      extracranial arteries should be the preferred goal of treatment in traumatic
      extracranial arteriovenous fistulas. The use of covered stents in the
      extracranial vessels can accomplish this goal.

PMID- 14656188
TI  - Surgical removal of self-expanding stents from the carotid artery: does the type
      of stent make a difference?
AB  - PURPOSE: To evaluate the degree of difficulty in surgically removing 2 different
      stent models placed in the canine carotid artery. METHODS: In 5 dogs, each
      carotid artery was stented with a braided Elgiloy self-expanding stent (BESES) on
      one side and a surface-spanning micro stent (SSMS) on the other. After 4 weeks,
      an arteriogram was obtained, and the stents were removed via direct surgical
      exposure. The minimum lengths of the skin incisions and arteriotomies, the ease
      of stent removal, and the presence of a distal intimal flap were recorded.
      RESULTS: Stent deployment and removal were successful in each animal, but there
      was a substantial difference in the ease of removal. The BESES could be removed
      in a strand-by-strand fashion via a more proximal, smaller arteriotomy compared
      to the SSMS (8.8+/-1.3 versus 37.2+/-4.7 mm, p<0.01). Furthermore, a smaller skin
      incision (3.85+/-0.9 versus 9.75+/-0.5 cm, p<0.01) was required for the BESES.
      There was no distal flap formation following BESES removal, whereas SSMS removal
      produced a large distal flap in each artery (p<0.01). CONCLUSIONS: Although rare,
      restenosis after stenting occurs, and surgical repair may become necessary in
      some patients. Each stent has inherent advantages and disadvantages, but the
      braided Elgiloy self-expanding stent lends itself to easier surgical removal,
      which may have important clinical implications, especially when used in the
      carotid artery.

PMID- 14656189
TI  - Transient ischemic attack due to early carotid stent thrombosis: successful
      rescue with rheolytic thrombectomy and systemic abciximab.
AB  - PURPOSE: To describe a successful neurorescue technique in a patient with
      generalized seizures followed by hemiparesis immediately after carotid artery
      stenting (CAS) for a postsurgical restenosis. CASE REPORT: A 65-year-old man with
      a symptomatic recurrent high-grade carotid stenosis after carotid endarterectomy
      was treated with CAS. The procedure was complicated by sudden transient ischemic
      attack caused by acute carotid stent thrombosis with clot propagation into the
      cerebral circulation. Percutaneous mechanical thrombectomy was performed with
      adjunctive infusion of intravenous abciximab, resulting in complete thrombus
      dissolution and resolution of neurological symptoms. CONCLUSIONS: Access to a
      mechanical thrombectomy device was essential for rapid thrombus extraction, and
      adjunctive abciximab aided in residual clot dissolution. As a result of this
      combined method of clot removal, a disastrous outcome was averted.

PMID- 14656190
TI  - Patient safety: who guards the patient.

PMID- 14656191
TI  - Contributions of the professional, public, and private sectors in promoting
      patient safety.
AB  - Patient safety has become a national priority. This article discusses the
      contributions of the professional, public, and private sectors regarding patient
      safety. Definitions and detailed examination of the issues surrounding patient
      safety are presented. Ideas to create improved systems for the important issue of
      patient safety are explored. The opportunity for increased interaction among the
      various groups has great potential. Health care organizations that exemplify best
      practices in patient safety will be rewarded by the purchasers of health care and
      by accreditation agencies. The Leapfrog Group and the Joint Commission on
      Accreditation of Health Care Organizations are leading this effort. Nursing has a
      major role in leading efforts to find solutions to advance patient safety
      standards.

PMID- 14656192
TI  - Health systems' accountability for patient safety.
AB  - Patient safety experts, including the Institute of Medicine Committee on Quality
      of Health Care in America, have emphasized the need to focus on systems failure
      as the source of most error in health care. This requires an emphasis on
      prevention and on health systems' accountability for error. This article
      discusses traditional and evolving approaches to systems' accountability for
      error. While there are some significant recent developments, such as the JCAHO
      new Patient Safety Goals, many issues remain about how to determine and enforce
      systems' accountability for error. These include identifying what systems will be
      held accountable for and how accountability will be enforced. While reporting of
      errors is one route toward accountability, many questions remain regarding the
      most effective approach toward error reporting. Research on and evaluation of
      reporting systems and other approaches toward systems' accountability will be
      important in moving forward in this area.

PMID- 14656193
TI  - The Professional Nursing Association's role in patient safety.
AB  - The purpose of this article is to describe the documents and activities of
      nursing's multipurpose, professional nursing association, the American Nurses
      Association, that promote patient safety. The roles of the professional nursing
      association in promoting the safety of the recipient of nursing care are
      numerous. These roles include developing and disseminating foundation documents,
      lobbying for legislation and regulations that protect and serve users of nursing
      services, and advocating for patients and issues which affect a nurse's ability
      to deliver safe care. Although the professional associations' usual purpose is to
      work for the welfare of the public, at times this can conflict with the
      association's need to advocate for its members. The professional association must
      balance the needs and interests of the association, the profession, and the
      public so as to promote the safety of patients receiving care.

PMID- 14656194
TI  - Care of patients with long-term indwelling urinary catheters.
AB  - The complications and management of long-term indwelling catheters used for
      urinary retention and incontinence were reviewed. Research evidence from 1992 -
      2002 was located through searches of CINAHL (38 articles), and Medline (89
      articles). Fifty studies were critiqued for this review. The most common
      complications of long-term indwelling catheters are bacteriuria, encrustation,
      and blockage. Less common is the prevalence of bacteremia and renal disease. Risk
      factors for bacteriuria include female gender, older age, and long-term
      indwelling catheter use. Urinary white blood cells are the best indicator of
      urinary tract infection. For drainable catheter systems used by community
      dwelling adults, daily bag cleaning with a diluted bleach solution (1:10) is
      effective in reducing bacterial counts to negligible numbers. Application of
      topical antibiotic cream to the meatus around the catheter does not reduce
      bacteriuria. Silicone catheters and larger lumen size catheters are more
      resistant to encrustation than other catheter types and smaller lumen size
      catheters. Acidifying the urine without removing the urease-producing bacteria
      does not reduce encrustation. Removal of catheter blockage is preventive for
      renal disease. Because of the complications of long-term indwelling catheter
      usage, periodic assessment and voiding trials should be used to determine the
      continued need for a catheter. Evidence-based recommendations for managing
      indwelling urinary catheters include screening for risk factors and evaluating
      urinary white blood cell count for infection, and assessment of the continued
      need for a catheter. Interventions include consideration of closed versus open
      drainage systems, type of catheter, and size of catheter lumen.

PMID- 14656195
TI  - Cancer-related fatigue.
AB  - Approximately 1.3 million people in the United States will be diagnosed with
      cancer in 2003 and millions of other individuals are already living with the
      disease. Fatigue continues to be the most prevalent and disruptive symptom of
      cancer and its treatment regimens. Fatigue was the most frequent and distressing
      cancer-related symptom occurring in women with lung cancer, two times greater
      than the next symptom, pain, and remains one of the most common symptoms in newly
      diagnosed lung cancer patients at any stage of the disease. There are many causes
      of cancer-related fatigue including preexisting conditions, physical and
      psychological symptoms caused by cancer, and the consequences of cancer
      treatment. High levels of fatigue decrease quality of life, physical functional
      status, and symptom management. This article presents an evidenced-base review of
      cancer-related fatigue, strategies for the management of cancer-related fatigue,
      and recommendations for clinical practice.

PMID- 14656196
TI  - Errors, the nursing shortage and ethics: survey results.

PMID- 14656197
TI  - The ethics of diversity: a call for intimate listening in thin places.

PMID- 14656198
TI  - Patient safety: a shared responsibility.
AB  - Patient safety is an essential and vital component of quality nursing care.
      However, the nation's health care system is prone to errors, and can be
      detrimental to safe patient care, as a result of basic systems flaws. A variety
      of stakeholders (society in general; patients; individual nurses; nursing
      educators, administrators, and researchers; physicians; governments and
      legislative bodies; professional associations; and accrediting agencies) are
      responsible for ensuring that patient care is safely delivered and that no harm
      occurs to patients. The responsibility of these stakeholders in addressing
      patient safety in the context of a nursing shortage is discussed, along with
      specific actions they have taken, and can continue to take, to promote safe care.

PMID- 14656199
TI  - An integrated analysis of nurse staffing and related variables: effects on
      patient outcomes.
AB  - The objective of this article is to synthesize much of the research done on nurse
      staffing and patient outcomes; the impact of organizational characteristics on
      nurse staffing patterns, patient outcomes, and costs; and the impact of nurses'
      experience on patient outcomes. The author concludes research indicates that
      nurse staffing has a definite and measurable impact on patient outcomes, medical
      errors, length of stay, nurse turnover, and patient mortality. Moreover, the
      literature reports data that help determine what is, indeed, appropriate
      staffing. Ratios are important--a consensus seems to be emerging supporting a
      range of from 4 to 6 patients per nurse in most acute care hospital inpatient
      settings, with no more than one to two patients per nurse in areas of high
      patient acuity. However, ratios must be modified by the nurses' level of
      experience, the organization's characteristics, and the quality of clinical
      interaction between and among physicians, nurses, and administrators.

PMID- 14656200
TI  - Endocrine and nutritional regulation of fetal adipose tissue development.
AB  - In the fetus, adipose tIssue comprises both brown and white adipocytes for which
      brown fat is characterised as possessing the unique uncoupling protein (UCP)1.
      The dual characteristics of fetal fat reflect its critical role at birth in
      providing lipid that is mobilised rapidly following activation of UCP1 upon cold
      exposure to the extra-uterine environment. A key stage in the maturation of fetal
      fat is the gradual rise in the abundance of UCP1. For species with a mature
      hypothalamic-pituitary axis at birth there is a gradual increase in the amount
      and activity of UCP1 during late gestation, in conjunction with an increase in
      the plasma concentrations of catecholamines, thyroid hormones, cortisol, leptin
      and prolactin. These may act individually, or in combination, to promote UCP1
      expression and, following the post-partum surge in each hormone, UCP1 abundance
      attains maximal amounts. Adipose tIssue grows in the fetus at a much lower rate
      than in the postnatal period. However, its growth is under marked nutritional
      constraints and, in contrast to many other fetal organs that are unaffected by
      nutritional manipulation, fat mass can be significantly altered by changes in
      maternal and, therefore, fetal nutrition. Fat deposition in the fetus is enhanced
      during late gestation following a previous period of nutrient restriction up to
      mid gestation. This is accompanied by increased mRNA abundance for the receptors
      of IGF-I and IGF-II. In contrast, increasing maternal nutrition in late gestation
      results in less adipose tIssue deposition but enhanced UCP1 abundance. The
      pronounced nutritional sensitivity of fetal adipose tIssue to both increased and
      decreased maternal nutrition may explain why the consequences of an adverse
      nutritional environment persist into later life.

PMID- 14656201
TI  - The molecular and cellular basis of corticosteroid resistance.
AB  - Corticosteroids (CS) can modulate gene expression and are often used to treat a
      range of immunological and inflammatory diseases such as asthma, inflammatory
      bowel disease and rheumatoid arthritis. However, a proportion of patients fail to
      show an adequate response. On this basis patients have been subdivided into CS
      sensitive (SS) and -resistant (SR) subgroups. The ability of CS to inhibit
      peripheral blood T cell proliferation in vitro has also been used similarly. In
      rheumatoid arthritis (RA), the in vitro-defined SS and SR subgroups correlate
      with the clinical responses to CS therapy. The mechanisms responsible for this
      observation are unknown but they appear to involve a number of known molecular
      events related to the described mechanisms of action of CS. These include
      alterations in the functional status of CS receptor-alpha, perturbations of the
      cytokine and hormonal milieu and intracellular signalling pathways. Peripheral
      blood mononuclear cells (MNCs) from SR significantly overexpress activated NF
      kappaB. In vitro, CS fail to significantly inhibit concanavalin A (conA)-induced
      NF-kappaB activation in MNCs from SR RA patients. The alterations in the
      intracellular signalling pathways may explain in part our observations seen in SR
      RA subjects, CS fail to significantly inhibit conA-induced interleukin (IL)-2 and
      IL-4 secretion and lipopolysaccharide-induced IL-8 and IL-1beta secretion in
      vitro. CS therapy fails to reduce the circulating levels of IL-8 and IL-1beta in
      RA patients. In asthma, CS fail to induce L10 in SR asthma patients. Other
      molecular mechanisms such as enhanced AP-1 expression and alterations in the MAP
      kinase pathway are most likely to be involved too and we are currently
      investigating such possibilities. A full understanding of the molecular basis of
      SR will lead to the development of more rational therapeutic strategies.

PMID- 14656202
TI  - Growth hormone therapy and Quality of Life: possibilities, pitfalls and
      mechanisms.
AB  - The actions of growth hormone (GH) are not restricted to growth: GH modulates
      metabolic pathways as well as neural, reproductive, immune, cardiovascular, and
      pulmonary physiology. The importance of GH in most physiological systems suggests
      that GH deficiency at any age would be associated with significant morbidity.
      However, prior to the advent of recombinant GH, cadaver-derived GH was only used
      therapeutically to correct the height deficit, and thereby hypothetically improve
      quality of life (QoL), in GH-deficient children. Physicians now have access to
      unlimited, albeit expensive, supplies of recombinant GH, and are considering the
      advisability of GH replacement or supplementation in other patient populations.
      This paper analyses studies investigating the relationship between GH and QoL in
      GH-deficient children or adults, in GH-replete short children suffering from
      idiopathic short stature, Turner syndrome, or intrauterine growth retardation and
      in GH-deficient or replete elderly adults. Possible mechanisms by which GH might
      improve QoL at neural and somatic sites are also proposed.

PMID- 14656204
TI  - Photoperiod and bromocriptine treatment effects on expression of prolactin
      receptor mRNA in bovine liver, mammary gland and peripheral blood lymphocytes.
AB  - Recent evidence suggests that photoperiod influences immune function.
      Interestingly, photoperiod has profound effects on concentrations of prolactin
      (PRL), a hormone also known to be involved in fluctuations of the immune system.
      However, the impact of photoperiod on PRL receptor (PRL-R) expression is poorly
      understood, particularly in tIssues of the immune system. Two experiments were
      performed to increase the general understanding of how photoperiod interacts with
      the immune system. Our first objective was to determine the effects of
      photoperiod on PRL-R mRNA expression and cellular immune function. Lymphocytes
      were isolated from blood collected from calves (n=10) and PRL-R mRNA expression
      of both long and short forms was quantified using real-time PCR. Lymphocytes
      expressed PRL-R mRNA, suggesting that PRL could act directly on these cells. To
      determine the relationship between photoperiod and PRL-R mRNA expression in other
      tIssues, hepatic and mammary biopsies were collected after calves were exposed to
      long days (LDPP; 16 h light:8 h darkness) or short days (SDPP; 8 h light:16 h
      darkness). Relative to LDPP, SDPP decreased circulating PRL, but increased
      expression of both forms of PRL-R mRNA in liver, mammary gland and lymphocytes.
      Short days also increased lymphocyte proliferation compared with long days.
      Reversal of photoperiodic treatments reversed the effects on circulating PRL, PRL
      R mRNA expression and lymphocyte proliferation. Our second objective was to
      manipulate PRL concentration in photoperiod-treated animals, using bromocriptine.
      Concentrations of PRL in LDPP animals injected daily with bromocriptine for 1
      week were decreased compared with LDPP controls, to a level similar to SDPP
      animals. Receptor expression was increased in LDPP+bromocriptine-treated animals
      relative to LDPP controls, as was lymphocyte proliferation. Overall, our results
      indicate that photoperiodic effects on PRL-R mRNA expression were inverse to
      those on circulating PRL, with short days stimulating expression of both forms of
      PRL-R mRNA. Expression of PRL-R mRNA changed in the same direction as lymphocyte
      proliferation with regard to photoperiod treatment, suggesting a link between
      photoperiodic effects on PRL sensitivity and immune function. Thus, PRL signaling
      may mediate photoperiodic effects on immune function.

PMID- 14656203
TI  - Migratory trophoblast cells express a newly identified member of the prolactin
      gene family.
AB  - Rodents possess an expanded prolactin (PRL) family of genes. These genes encode
      for a family of structurally related hormones/cytokines that are expressed most
      prominently in the anterior pituitary, uterus and placenta. In this study, we
      have identified a new member of the rat PRL family through a search of the
      National Center for Biotechnology Information expressed sequence database. The
      cDNA was sequenced and its corresponding mRNA characterized. On the basis of
      existing nomenclature, the rat cDNA was termed PRL-like protein-N (PLP-N). PLP-N
      has structural features indicative of its inclusion in the PRL family and is most
      closely related to PRL-like protein-F (PLP-F) and proliferin related protein (PLF
      RP). A survey of PLP-N mRNA expression by Northern analysis indicated that PLP-N
      showed extensive expression in the metrial gland and minimal expression in the
      chorioallantoic placenta or other tIssues. Expression of PLP-N mRNA was
      restricted to migratory trophoblast cells. Junctional zone trophoblast cells
      isolated from day 13 of gestation placenta differentiated in vitro and exhibited
      a capacity for PLP-N expression. In summary, we have discovered a new member of
      the PRL family that is prominently expressed in migratory trophoblast cells
      residing in the metrial gland.

PMID- 14656205
TI  - Effects of acute prolactin manipulation on sexual drive and function in males.
AB  - The neuroendocrine response to sexual activity in humans is characterized by a
      pronounced orgasm-dependent increase of plasma levels of prolactin. In contrast
      to the well-known inhibitory effects of chronic hyperprolactinemia on sexual
      drive and function, the impact of acute prolactin alterations on human sexual
      physiology is unknown. Therefore, this study was designed to investigate the
      effects of acute manipulation of plasma prolactin on sexual behavior. Ten healthy
      males participated in a single-blind, placebo-controlled, balanced cross-over
      design. Prolactin levels were pharmacologically increased to high levels
      (protirelin, 50 micro g i.v.) or reduced to low physiological concentrations
      (cabergoline, 0.5 mg p.o.). Sexual arousal and orgasm were then induced by an
      erotic film and masturbation. In addition to continuous neuroendocrine and
      cardiovascular recordings, the quality and intensity of the acute sexual drive,
      arousal, orgasm and refractory period were assessed by extensive psychometric
      measures. Administration of cabergoline decreased prolactin levels and
      significantly enhanced all parameters of sexual drive (P<0.05), function (P<0.01)
      and positive perception of the refractory period (P<0.01). Administration of
      protirelin increased prolactin concentrations and produced small, but not
      significant reductions of sexual parameters. The sexual effects observed from
      cabergoline were completely abrogated by coadministration of protirelin. Although
      different pharmacological sites of action of prolactin-altering drugs have to be
      considered, these data demonstrate that acute changes in prolactin plasma levels
      may be one factor modulating sexual drive and function. Therefore, besides a
      neuroendocrine reproductive reflex, a post-orgasmic prolactin increase may
      represent one factor modulating central nervous system centers controlling sexual
      drive and behavior. These findings may offer a new pharmacological approach for
      the treatment of sexual disorders.

PMID- 14656206
TI  - Plasma protein regulation by thyroid hormone.
AB  - Thyroid hormones (THs) regulate growth, development, differentiation and
      metabolic processes by interacting and activating thyroid hormone receptors
      (TRs). Although much progress has been made in our understanding of the
      transcriptional regulation of many TR target genes, little is known of the
      regulation of plasma protein gene expression by TRs. To investigate the role of
      TRs in plasma protein expression we used human hepatocellular carcinoma cell
      lines and carried out cDNA microarray analysis. Our results indicate that several
      plasma proteins including transferrin, prothrombin, angiotensinogen, haptoglobin,
      alpha-2-HS-glycoprotein alpha and beta chain, complement, lipoproteins and
      fibrinogen are up-regulated by THs. Furthermore, clusterin, alpha-2-macroglobulin
      precursor, prothymosin alpha and alpha-fetoprotein were found to be down
      regulated by THs.Transferrin, an iron-binding protein expressed in all mammals,
      and mainly synthesized in the liver, was investigated further. Immunoblot and
      Northern blot analyses revealed that exposure of HepG2-TRalpha1 sub-lines and
      HepG2-Neo cells to tri-iodothyronine (T(3)) induced time- and dose-dependent
      increases in the abundance of transferrin mRNA and protein, with the extent of
      these effects correlating with the level of expression of TRalpha1. Nuclear run
      on experiments indicate that this induction is functioning at the transcriptional
      level. Moreover, cyclohexamide treatment did not eliminate the induction of
      transferrin by TH. Thus, our results suggest that the induction of transferrin by
      TH is direct and may in fact be mediated by an as yet unidentified response
      element in the promoter region.

PMID- 14656207
TI  - Zonal expression of the thyroid hormone receptor alpha isoforms in rodent liver.
AB  - Many metabolic processes occur simultaneously in the liver in different locations
      along the porto-central axis of the liver units. These processes are often
      regulated by hormones, one of which is thyroid hormone which for its action
      depends on the presence of the different isoforms of the thyroid hormone receptor
      (TR). These are encoded by two genes: c-erbA-alpha encoding TRalpha1 and TRalpha2
      and their respective Delta isoforms, and c-erbA-beta which encodes TRbeta1,
      TRbeta2 and TRbeta3. We recently found a zonal (pericentral) expression of and a
      diurnal variation in the TRbeta1 isoform in rat liver. We were therefore also
      interested to see whether TRalpha1 and TRalpha2 expression showed similar
      characteristics. For this reason we raised both polyclonal and monoclonal
      antibodies against TRalpha1 and TRalpha2 isoforms and characterised these.
      Antibody specificity was tested using Western blots and immunohistochemistry in
      liver of TR isoform-specific knockout animals. Using these antibodies we found
      that the TRalpha1 and TRalpha2 isoforms are zonally expressed around the central
      vein in rat liver. The experiments show that the portal to central gradient of
      TRalpha1 is broader than that of TRbeta1. Moreover, the expression of the
      TRalpha2 protein showed a diurnal variation with a peak in the afternoon when the
      animals are least active whereas no such variation was found for the TRalpha1
      protein. From our data it appears that both the TRalpha1 and TRalpha2 isoforms
      show a zonal distribution in liver. This finding, together with the observed
      diurnal rhythm, has major implications for interpreting and timing experiments
      concerning the TR and its downstream actions in liver.

PMID- 14656208
TI  - Production of multiple cytokines and induction of cachexia in athymic nude mice
      by a new anaplastic thyroid carcinoma cell line.
AB  - An anaplastic thyroid cancer cell line, Thena, was recently established in our
      laboratory following radical thyroidectomy of a patient with anaplastic thyroid
      cancer. Microscopically, Thena cells were spindle-shaped or small round cells.
      Thena cells were reactive with cytokeratin AE1/AE3 antibodies, epithelial
      membrane antigen, interleukin (IL)-6, epithelial growth factor receptor,
      transforming growth factor (TGF)-alpha, vascular endothelial growth factor, and
      vimentin. Thena cells secreted high levels of IL-6, leukemia inhibitor factor
      (LIF), tumor necrosis factor (TNF)-alpha, and TGF-beta1 in the culture
      supernatants, as determined by enzyme-linked immunosorbent assay. When
      subcutaneously injected with Thena cells, athymic nude mice developed tumor
      masses in the skin within 2 weeks. Furthermore, Thena cells induced cachexia in
      these tumor-bearing mice. High levels of human IL-6, LIF and TGF-beta1 were
      detected in the mouse sera. To our knowledge, the Thena cell line is the first
      thyroid cancer cell line reported to induce cachexia in nude mice. This cachectic
      animal model is worthy of further study to explore the treatment of thyroid
      cancer-induced cachexia.

PMID- 14656209
TI  - Carboxy derivatives of isoflavones as affinity carriers for cytotoxic drug
      targeting in adrenocortical H295R carcinoma cells.
AB  - Carboxy derivatives of isoflavones that exhibit oestrogenic/anti-oestrogenic
      properties were used as carriers for affinity drug targeting to H295R
      adrenocortical carcinoma cells that express transcripts of oestrogen receptor
      (ER) alpha and beta. These derivatives were prepared by introducing a
      carboxymethyl group at the 6-position of genistein and of biochanin A, yielding
      6CG and 6CB respectively. In transactivation assays, 6CG displayed mixed
      agonist/antagonist activity for ERalpha, whereas 6CB displayed only weak
      antagonist activity. Low concentrations of oestrogen, 6CG and 6CB were capable of
      inducing proliferation in H295R cells and of stimulating creatine kinase (CK)
      specific activity, suggesting that these cells were sensitive to oestrogenic
      compounds. In in vivo experiments, both 6CG and 6CB were capable of inhibiting
      oestrogen-induced CK specific activity in rat tIssues. For affinity drug
      targeting, the cytotoxic drug daunomycin was coupled to 6CB and 6CG, yielding 6CB
      Dau and 6CG-Dau respectively. These conjugates were tested for their
      antiproliferative ability to inhibit DNA synthesis as assessed by incorporation
      of [(3)H]thymidine in H295R cells. A dose-dependent cytoxicity was observed with
      both conjugates. At 0.3-3 nM, both conjugates were 10 to 30 times more potent
      than daunomycin. At 30 nM these conjugates were two to three times more potent
      than daunomycin. At concentrations ranging between 300 and 3000 nM, no difference
      in cytotoxicity was observed between the conjugates and daunomycin. When the
      cells were treated over a wide range of concentrations with a combination of 6CG
      plus daunomycin, the observed cytotoxicity was less than with daunomycin alone.
      When non-transformed rat enterocytes, which do not express ER, were treated with
      6CG-Dau or daunomycin, the antiproliferative effect of 6CG-Dau was the same as
      that of daunomycin over the concentration range tested. These pilot studies
      suggest that the ready availability of oestrogenic binding sites in H295R cells
      can be exploited for site-directed chemotherapy.

PMID- 14656210
TI  - Interleukin-1beta (IL-1beta) and IL-6 modulate insulin-like growth factor-binding
      protein (IGFBP) secretion in colon cancer epithelial (Caco-2) cells.
AB  - Chronic inflammation is characterised by modifications in cytokine
      concentrations, whereas growth is mainly dependent on the GH-IGF axis. IGF-I
      bioavailability is modulated by a family of IGF-binding proteins (IGFBPs). The
      aim of the present study was to evaluate the interactions among interleukin-1beta
      (IL-1beta), IL-6 and IGFBP secretion by intestinal cells to assess whether
      cytokines modulate IGFBP secretion, and in turn IGF-I and IGF-II bioavailability.
      The human colon carcinoma derived cell line Caco-2 was used as an in vitro model
      for its capacity to differentiate spontaneously. Experiments were carried out on
      day 4 (undifferentiated state) and day 14 (differentiated state) after plating.
      Carcinoembryonic antigen (CEA) was used as a marker of differentiation and
      increased in the conditioned media (CM) from days 4 to 14 (0.2+/-0.01 ng/ml per
      10(5) cells vs 3.3+/-0.2 ng/ml per 10(5) cells, P<0.05). IGFBP-2 and IGFBP-4
      secretion decreased concomitantly. Cells were stimulated with IL-1beta and IL-6
      at 1, 10 and 50 ng/ml, and with IL-1beta and IL-6 in combination at the same dose
      of 1 and 10 ng/ml. IGF-I at 50 ng/ml was used as a control. Caco-2 cells
      expressed and secreted mainly IGFBP-2 and IGFBP-4 into the CM. On day 4, IL-1beta
      (1 ng/ml) and IL-6 (10 and 50 ng/ml) reduced IGFBP-2 by 29+/-8%, and by 32+/-9
      and 38+/-8% respectively (P<0.05). IGFBP-4 was also reduced by IL-1beta at 1 and
      50 ng/ml (-14+/-4% and -46+/-11% vs serum free medium (SFM) respectively,
      P<0.05), and IL-6 at 50 ng/ml (-46+/-15%, P<0.05). Both IGFBP-2 and IGFBP-4 were
      reduced by IL-1beta and IL-6 in combination at 1 and 10 ng/ml (P<0.05). On day
      14, IGFBP-2 band intensity was reduced at 10 ng/ml of IL-1beta (-22+/-15% vs SFM,
      P<0.05) and at 50 ng/ml of both cytokines (-33%+/-8% and -13%+/-13% vs baseline
      respectively, P<0.05). IGFBP-4 band intensity decreased with 10 and 50 ng/ml of
      IL-1beta (-35+/-11% and -46+/-15% vs SFM respectively) and IL-6 (-36%+/-10% and 
      46+/-15% vs SFM respectively). IL-1beta and IL-6 in combination at 1 and 10 ng/ml
      reduced both IGFBP-2 and IGFBP-4.In conclusion, IGFBP-2 and IGFBP-4 secretion in
      CM decreased with Caco-2 cell differentiation. IGFBP-2 and IGFBP-4 were
      significantly decreased by IL-1beta and IL-6 treatment in both the
      undifferentiated and differentiated state. Furthermore, these cytokines increased
      cell proliferation whereas total protein content was significantly reduced only
      at the higher concentrations of IL-6 and IL-1beta. These findings suggest that
      interleukins modulate the IGF-IGFBP system in Caco-2 cells in vitro.

PMID- 14656211
TI  - The inducible isoform of CREM (inducible cAMP early repressor, ICER) is a
      repressor of CYP19 rat ovarian promoter.
AB  - The synthesis of estradiol by the granulosa cells is a prominent event in ovarian
      physiology and depends on the expression of P450(AROM). FSH induces the
      expression of P450(AROM) in granulosa cells as a result of the presence in the
      ovarian promoter of a CRE (cAMP response element)-like sequence (CLS). In
      rodents, LH downregulates aromatase expression during luteinization by an as yet
      undescribed mechanism. In granulosa cells, LH increases the expression of the
      inducible cAMP early repressor (ICER), an isoform of CREM (cAMP-responsive
      element modulator) that represses cAMP-induced transcription. The possibility
      that ICER represses the activity of the aromatase ovarian promoter, thus being
      part of the mechanism underlying the effects of LH was investigated. We have
      found that: (1) nuclear proteins from forskolin-stimulated granulosa cells were
      specifically bound to an oligonucleotide containing the CLS sequence of the CYP19
      ovarian promoter and one out of the two protein-DNA complexes formed was
      supershifted by an anti-CREM antibody; (2) in granulosa cells, forskolin-induced
      increases in P450(AROM) promoter luciferase reporter gene activity were prevented
      by the transient overexpression of ICER; (3) similar results were obtained in 8
      Br-cAMP-stimulated R2C cells, a Leydig tumor cell line routinely used for the
      study of P450(AROM) promoter activity; (4) both ICER mRNA levels and P450(AROM)
      promoter-driven luciferase activity were elevated 6 and 12 h after stimulation of
      R2C cells with 8-Br-cAMP and were decreased 24 and 48 h later; (5) in an R2C
      polyclonal line overexpressing ICER, the promoter activity at early stages of
      stimulation was completely attenuated, while 24 and 48 h downregulation was
      prevented in another R2C line stably transfected with an antisense ICER
      construct. These results suggest that ICER represses CYP19 ovarian promoter and
      that LH-induced expression of ICER may serve to downregulate P450(AROM)
      transcription in granulosa cells during luteinization.

PMID- 14656212
TI  - The response of the hepatic insulin-like growth factor system to growth hormone
      and dexamethasone in calves.
AB  - Glucocorticoids inhibit postnatal growth and yet can stimulate the somatotropic
      axis around birth. The aim of the present study was to investigate the effects of
      dexamethasone on the somatotropic axis and on the responses of the insulin-like
      growth factor (IGF) system to growth hormone treatment in calves. Calves (n=24)
      were randomly divided into four groups. Group DX was injected with dexamethasone
      (30 micro g/kg body weight per day), group GH was injected with 500 mg slow
      release bovine growth hormone at 14-day intervals, group GHDX was injected with
      dexamethasone and bovine growth hormone, and group CNTRL (serving as control) was
      injected with saline from day 3 to day 42 of life. Blood samples were taken on
      day 3 and blood and liver samples were obtained on days 7, 14, 28 and 42. Body
      weight increased in the CNTRL and GH groups up to the end of the study and in the
      DX and GHDX groups up to the fourth week. Dexamethasone treatment decreased
      (P<0.05) plasma IGF binding protein (IGFBP)-1 on days 7 and 14, but increased
      (P<0.05) plasma IGFBP-1, decreased (P<0.05) plasma IGF-I and IGFBP-3, and
      decreased hepatic mRNA for growth hormone receptor (GHR) and IGF-I on day 42.
      Growth hormone treatment increased (P<0.05) plasma growth hormone concentrations
      on days 7 and 14, tended to increase (P<0.1) plasma IGF-I concentrations on day
      42, and increased (P<0.05) hepatic mRNA levels of GHR on day 14 and IGF-I mRNA
      levels on days 7 and 14. The combined dexamethasone and growth hormone treatment
      increased plasma growth hormone concentrations on day 7 and resulted in the
      highest plasma concentrations of IGF-I and IGFBP-3 (day 7 to day 28) as well as
      the greatest abundance of hepatic GHR (day 14) and IGF-I (days 7 and 14) mRNA.
      Plasma IGFBP-1 concentrations in the GHDX group behaved in a similar manner as in
      the DX group. In conclusion, the response of the somatotropic axis to growth
      hormone treatment could be greatly enhanced by dexamethasone treatment during the
      neonatal and early postnatal period, but body weight gain was not improved.
      Dexamethasone alone inhibited the somatotropic axis and postnatal growth after
      the first Month of life.

PMID- 14656213
TI  - Effects of food restriction and pregnancy on the expression of insulin-like
      growth factors-I and -II in tIssues from guinea pigs.
AB  - The insulin-like growth factor (IGF) system is subjected to pregnancy-associated
      changes in the circulation and is suggested to be of importance for partitioning
      of nutrients between the mother and the foetus. Interestingly, maternal
      undernutrition alters the pregnancy-associated changes, with possible adverse
      consequences for the mother and the foetus. However, it is not known how
      malnutrition and pregnancy alter the expression of mRNA for IGFs locally in
      different tIssues. The aims of this study were to investigate where IGF-I and IGF
      II are expressed in guinea pigs and how this expression is altered during food
      restriction and pregnancy. Ad libitum-fed and food-restricted (fed 70% of the ad
      libitum-fed intake four weeks before pregnancy and throughout the study) guinea
      pigs were mated. On day 40 of pregnancy and on the corresponding day for virginal
      females the animals were killed. mRNA for IGF-I and IGF-II was analysed in
      various organs/tIssues by solution hybridisation. mRNA for IGF-I was expressed in
      high amounts in uterus, liver and adipose tIssues. The expression was not
      affected by food restriction, but was increased in liver and adipose tIssue and
      decreased in uterus by pregnancy. mRNA for IGF-II was expressed in high amounts
      in the placenta and liver. In the placenta the expression was decreased by food
      restriction. Pregnancy increased the levels of mRNA for IGF-II in the liver. Food
      restricted dams had smaller foetuses and placentas. In conclusion, this study
      indicates an important role for the adipose tIssue during gestation, not only as
      an energy store but also as an endocrine tIssue expressing IGF-I. The decreased
      expression of IGF-II in the placenta due to food restriction is suggested to have
      adverse effects on placental structure and function.

PMID- 14656214
TI  - A comparative study of amino acid consumption by rat islet cells and the clonal
      beta-cell line BRIN-BD11 - the functional significance of L-alanine.
AB  - Evidence has been published that L -alanine may, under appropriate conditions,
      promote insulin secretion in normal rodent islets and various beta cell lines.
      Previous results utilising the clonal beta-cell line BRIN-BD11, demonstrated that
      alanine dramatically elevated insulin release by a mechanism requiring oxidative
      metabolism. We demonstrate in this paper that addition ofL -alanine had an
      insulinotropic effect in dispersed primary islet cells. Addition of D -glucose
      increasedL -alanine consumption in both BRIN-BD11 cells and primary islet cells.L
      -glutamine consumption in the BRIN-BD11 cell line and primary rat islets was also
      determined. The consumption rate was in line with that previously reported for
      cells of the immune system and other glutamine-utilising cells or tIssues.
      However,L -alanine consumption was at least an order of magnitude higher thanL 
      glutamine consumption. The metabolism ofL -alanine in the beta-cell may result in
      stimulation of insulin secretion via generation of metabolic stimulus secretion
      coupling factors such asL -glutamate.

PMID- 14656215
TI  - Attractin' more attention - new pieces in the obesity puzzle?
AB  - Genetic, biochemical and pharmacological studies in humans and rodents have
      established that signalling through the G-protein-coupled melanocortin-4 receptor
      (MC4R) by pro-opiomelanocortin (POMC)-derived ligands plays a critical role in
      the central suppression of appetite. As a consequence, malfunction of this
      signalling system leads to the development of obesity. It has been shown
      previously that melanocortin signalling can be modulated by the type 1
      transmembrane protein attractin, apparently acting as a co-receptor for the
      inhibitory ligand agouti. Work reported in this issue of Biochemical Journal
      (Haqq et al.) demonstrates that the cytosolic tail of an attractin-like protein
      (ALP) binds directly and specifically to the C-terminal region of MC4R, raising
      the possibility that proteins of the attractin family influence melanocortin
      receptor function through multiple mechanisms.

PMID- 14656217
TI  - Can mild-to-moderate hyperhomocysteinaemia impair endothelial function in the
      absence of other risk factors for cardiovascular disease?
AB  - The majority of clinical studies demonstrate that patients with
      hyperhomocysteinaemia have an increased risk of atherothrombotic events. However,
      there is a striking and poorly understood heterogeneity in the severity of
      clinical features in individuals with hyperhomocysteinaemia. This observation
      suggests that other factors must exist that modulate the relationship between
      hyperhomocysteinaemia and clinical disease. Therefore identifying factors that
      inhibit or enhance the vasculotoxic effects of homocysteine is important, as is
      elucidation of how homocysteine damages blood vessels. This comment discusses the
      study of Woodman and colleagues in this issue of Clinical Science in which they
      investigate the effects of hyperhomocysteinaemia on endothelial function.

PMID- 14656216
TI  - Role of receptor tyrosine kinases in G-protein-coupled receptor regulation of
      Ras: transactivation or parallel pathways?
AB  - Ras protein regulation by G-protein-coupled receptors has been thought to occur
      through transactivation of receptor tyrosine kinases. New evidence suggests that
      these two receptor types independently control different pathways leading to Ras
      activation in response to lysophosphatidic acid (LPA). Epidermal growth factor
      receptor function is needed for basal nucleotide exchange on Ras, whereas the LPA
      receptor controls an inducible exchange activity.

PMID- 14656218
TI  - Guanine nucleotide dissociation inhibitor activity of the triple GoLoco motif
      protein G18: alanine-to-aspartate mutation restores function to an inactive
      second GoLoco motif.
AB  - GoLoco ('Galpha(i/o)-Loco' interaction) motif proteins have recently been
      identified as novel GDIs (guanine nucleotide dissociation inhibitors) for
      heterotrimeric G-protein alpha subunits. G18 is a member of the mammalian GoLoco
      motif gene family and was uncovered by analyses of human and mouse genomes for
      anonymous open-reading frames. The encoded G18 polypeptide is predicted to
      contain three 19-amino-acid GoLoco motifs, which have been shown in other
      proteins to bind Galpha subunits and inhibit spontaneous nucleotide release.
      However, the G18 protein has thus far not been characterized biochemically. Here,
      we have cloned and expressed the G18 protein and assessed its ability to act as a
      GDI. G18 is capable of simultaneously binding more than one Galpha(i1) subunit.
      In binding assays with the non-hydrolysable GTP analogue guanosine 5'-[gamma
      thio]triphosphate, G18 exhibits GDI activity, slowing the exchange of GDP for GTP
      by Galpha(i1). Only the first and third GoLoco motifs within G18 are capable of
      interacting with Galpha subunits, and these bind with low micromolar affinity
      only to Galpha(i1) in the GDP-bound form, and not to Galpha(o), Galpha(q),
      Galpha(s) or Galpha12. Mutation of Ala-121 to aspartate in the inactive second
      GoLoco motif of G18, to restore the signature acidic-glutamine-arginine
      tripeptide that forms critical contacts with Galpha and its bound nucleotide
      [Kimple, Kimple, Betts, Sondek and Siderovski (2002) Nature (London) 416, 878
      881], results in gain-of-function with respect to Galpha binding and GDI
      activity.

PMID- 14656219
TI  - Glycoproteins VI and Ib-IX-V stimulate tyrosine phosphorylation of tyrosine
      kinase Syk and phospholipase Cgamma2 at distinct sites.
AB  - Glycoproteins GPVI and GPIb-IX-V stimulate robust tyrosine phosphorylation of Syk
      and PLCg2 (phospholipase Cg2) in washed platelets, but only the former stimulates
      pronounced activation of phospholipase. Using phospho-specific antibodies, we
      demonstrate that GPVI, but not GPIb-IX-V, stimulates significant tyrosine
      phosphorylation of Syk at the autophosphorylation site pY525/526, a marker of Syk
      activity. In addition, GPVI stimulates tyrosine phosphorylation of PLCg2 at
      Tyr753 and Tyr759, whereas GPIb-IX-V only induces significant phosphorylation at
      Tyr753. Both receptors stimulate tyrosine phosphorylation of Btk at the
      regulatory Tyr223 and Tyr551. Syk and Btk phosphorylate peptides from PLCg2
      containing Tyr753 and Tyr759 respectively, suggesting that they may stimulate
      phosphorylation at these sites in phospholipase. Studies using PLCg2-deficient
      platelets demonstrated that phospholipase is not required for the activation of
      integrin aIIbb3 by GPIb-IX-V. Our results demonstrate fundamental differences
      between GPVI and GPIb-IX-V in the regulation of tyrosine phosphorylation of Syk
      and PLCg2 consistent with the functional impairment of phospholipase in
      signalling by GPIb-IX-V.

PMID- 14656220
TI  - Induction of fibroblast apolipoprotein E expression during apoptosis, starvation
      induced growth arrest and mitosis.
AB  - Apolipoprotein E (apoE) mediates the hepatic clearance of plasma lipoproteins,
      facilitates cholesterol efflux from macrophages and aids neuronal lipid
      transport. ApoE is expressed at high levels in hepatocytes, macrophages and
      astrocytes. In the present study, we identify nuclear and cytosolic pools of apoE
      in human fibroblasts. Fibroblast apoE mRNA and protein levels were up-regulated
      during staurosporine-induced apoptosis and this was correlated with increased
      caspase-3 activity and apoptotic morphological alterations. Because the
      transcription of apoE and specific pro-apoptotic genes is regulated by the
      nuclear receptor LXR (liver X receptor) alpha, we analysed LXRalpha mRNA
      expression by quantitative real-time PCR and found it to be increased before apoE
      mRNA induction. The expression of ABCA1 (ATP-binding cassette transporter A1)
      mRNA, which is also regulated by LXRalpha, was increased in parallel with apoE
      mRNA, indicating that LXRalpha probably promotes apoE and ABCA1 transcription
      during apoptosis. Fibroblast apoE levels were increased under conditions of serum
      starvation-induced growth arrest and hyperoxia-induced senescence. In both cases,
      an increased nuclear apoE level was observed, particularly in cells that
      accumulated lipofuscin. Nuclear apoE was translocated to the cytosol when mitotic
      nuclear disassembly occurred and this was associated with an increase in total
      cellular apoE levels. ApoE amino acid sequence analysis indicated several
      potential sites for phosphorylation. In vivo studies, using 32P-labelling and
      immunoprecipitation, revealed that fibroblast apoE can be phosphorylated. These
      studies reveal novel associations and potential roles for apoE in fundamental
      cellular processes.

PMID- 14656221
TI  - Functional features and genomic organization of mouse NaCT, a sodium-coupled
      transporter for tricarboxylic acid cycle intermediates.
AB  - In the present study, we report on the molecular cloning and functional
      characterization of mouse NaCT (Na+-coupled citrate transporter), the mouse
      orthologue of Drosophila Indy. Mouse NaCT consists of 572 amino acids and is
      highly similar to rat and human NaCTs in primary sequence. The mouse nact gene
      coding for the transporter is approx. 23 kb long and consists of 12 exons. When
      expressed in mammalian cells, the cloned transporter mediates the Na+-coupled
      transport of citrate and succinate. Competition experiments reveal that mouse
      NaCT also recognizes other tricarboxylic acid cycle intermediates such as malate,
      fumarate and 2-oxo-glutarate as excellent substrates. The Michaelis-Menten
      constant for the transport process is 38+/-5 mM for citrate and 37+/-6 mM for
      succinate at pH 7.5. The transport process is electrogenic and exhibits an
      obligatory requirement for Na+. Na+-activation kinetics indicates that multiple
      Na+ ions are involved in the activation process. Extracellular pH has a
      differential effect on the transport function of mouse NaCT depending on whether
      the transported substrate is citrate or succinate. The Michaelis-Menten constants
      for these substrates are also influenced markedly by pH. When examined in the
      Xenopus laevis oocyte expression system with the two-microelectrode voltage-clamp
      technique, the transport process mediated by mouse NaCT is electrogenic. The
      charge-to-substrate ratio is 1 for citrate and 2 for succinate. The most probable
      transport mechanism predicted by these studies involves the transport of citrate
      as a tervalent anion and succinate as a bivalent anion with a fixed Na+/substrate
      stoichiometry of 4:1. The present study provides the first unequivocal evidence
      for the electrogenic nature of mammalian NaCT.

PMID- 14656222
TI  - HNF1alpha is involved in tissue-specific regulation of CFTR gene expression.
AB  - The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a
      complex pattern of expression with tissue-specific and temporal regulation.
      However, the genetic elements and transcription factors that control CFTR
      expression are largely unidentified. The CFTR promoter does not confer tissue
      specificity on gene expression, suggesting that there are regulatory elements
      outside the upstream region. Analysis of potential regulatory elements defined as
      DNase 1-hypersensitive sites within introns of the gene revealed multiple
      predicted binding sites for the HNF1alpha (hepatocyte nuclear factor 1alpha)
      transcription factor. HNF1alpha, which is expressed in many of the same
      epithelial cell types as CFTR and shows similar differentiation-dependent changes
      in gene expression, bound to these sites in vitro. Overexpression of heterologous
      HNF1alpha augmented CFTR transcription in vivo. In contrast, antisense inhibition
      of HNF1 alpha transcription decreased the CFTR mRNA levels. Hnf1 alpha knockout
      mice showed lower levels of CFTR mRNA in their small intestine in comparison with
      wild-type mice. This is the first report of a transcription factor, which confers
      tissue specificity on the expression of this important disease-associated gene.

PMID- 14656224
TI  - Haematology and palliative care: blood, sweat and tears.

PMID- 14656225
TI  - Sharpening the clinical diagnostic borders of chronic obstructive pulmonary
      disease.

PMID- 14656226
TI  - Global climate change: will it affect vector-borne infectious diseases?

PMID- 14656227
TI  - New treatment for Ecstasy-related hyperthermia.

PMID- 14656228
TI  - How well do doctors know their patients with severe asthma?
AB  - BACKGROUND: Rates of asthma mortality have fallen in Australia since the
      commencement of the National Asthma Campaign and promotion of the Australian
      asthma management plan. New strategies are now needed to further reduce
      mortality. AIM: To examine agreement about key features between asthma patients
      and their general practitioners (GPs). METHODS: We interviewed: (i) the next of
      kin of 56 asthma deaths, (ii) 91 asthma patients presenting to emergency
      departments with acute severe asthma and (iii) 147 of their GPs. RESULTS:
      Agreement was substantial for usage of oral symptomatic medication, but poor for
      inhaled symptomatic and preventive medications. There was moderate agreement
      regarding hospital admissions within the last 12 months among the cases, but
      little about other markers of severity. There was moderate agreement where the
      presenting or fatal attack was triggered by an upper respiratory-tract infection
      or aspirin. The next of kin and GPs agreed about family problems, but not about
      other psychosocial issues. They also agreed about which cases had been given
      action plans or verbal instructions, but few other aspects of asthma management.
      There was also moderate agreement regarding the use of peak flow meters by the
      controls. CONCLUSIONS: Doctors often have relatively poor insights into self
      management practices, social background or trigger factors, even in high-risk
      patients. This should be considered when planning future campaigns to improve
      asthma management and further reduce mortality.

PMID- 14656229
TI  - Australasian haematologist referral patterns to palliative care: lack of
      consensus on when and why.
AB  - BACKGROUND: Patients with haematological malignancies are not referred to
      palliative care services as frequently as those with solid cancers (non
      haematological malignancies). AIMS: The present study surveyed haematologists in
      Australia and New Zealand. We aimed to record theoretical referral times,
      identify problems with referral to palliative care and clarify elements used to
      decide whether a patient was "terminally ill". METHODS: A questionnaire based on
      the case-histories of three patients (with acute leukaemia, lymphoma or multiple
      myeloma) was distributed at the Haematology Society of Australia and New Zealand
      Congress 2000, Perth, Australia. Each case was divided into stages by
      transitional points in the illness to include issues or prognostic variables that
      may stimulate referral to palliative care. Questions were asked about: (i)
      referral-triggers, (ii) problems previously experienced, (iii) definition of when
      the patient was "terminally ill", (iv) prognostication difficulties and (v)
      communication about prognosis. RESULTS: The response rate was 11%, which may
      represent up to 32% of Australian specialists. Eighty per cent had access to all
      types of palliative care services and refer for symptom control, regardless of
      illness stage. Twenty-nine per cent had experienced difficulties in referring.
      There was a variation as to exactly when referral would occur and when each case
      was considered "terminally ill". Reasons for early or later referral were
      explored. Prognostication difficulties were common. CONCLUSIONS: In theory there
      is a willingness to refer to palliative care, however this has yet to be
      translated to day-to-day practice. This may be due to prognostication
      difficulties, logistical factors and medical concerns. Models of referral are
      suggested for further study.

PMID- 14656230
TI  - Bronchodilator reversibility in Australian adults with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND AND AIMS: Bronchodilator reversibility (BDR) and inhaled
      corticosteroid (ICS) use were assessed for volunteers who responded to an
      advertisement requesting current or ex-smokers who were experiencing
      breathlessness to attend for lung function testing. METHODS: One hundred and
      fifty-four volunteers responded. Forced expiratory volume (FEV1) was measured
      before and after 400 microg of salbutamol. Significant BDR was assessed according
      to guidelines of: (i) the American Thoracic Society (> or =12% plus 200 mL of
      baseline FEV1 or forced vital capacity), (ii) the British-Thoracic Society (BTS)
      (> or =15% plus 200 mL of baseline FEV1), (iii) the European Thoracic Society (>
      or =10% predicted FEV1), and (iv) the most commonly used criteria in Australia
      and New Zealand (> or =15% of baseline FEV1). RESULTS: One hundred and twenty
      three subjects (33 female; 40 current smokers; median pack years 48 (range 5
      144)) were suitable for analysis (i.e. had no history of asthma, demonstrable
      airflow limitation and a forced expiratory ratio (FER) of <70%). Twenty (16%)
      patients had an FEV1 within the normal range but FER of <70%, 24 (20%) patients
      had mild disease (FEV1 60-80% predicted), 31 (24%) patients had moderate disease
      (FEV1 40-59% predicted), and 48 (39%) patients had severe disease (FEV1 <40%
      predicted), according to BTS criteria. Significant BDR was evident in: (i) 58
      (47%) subjects by American criteria, (ii) 26 (21%) subjects by British criteria,
      (iii) 19 (15%) subjects by European criteria and (iv) 36 (29%) subjects by
      Australasian criteria. ICS use was reported by 71 (58%) subjects overall and was
      weakly, but significantly, related to poorer FEV1 (r = -0.2; P < 0.01), and
      greater BDR (r = 0.3; P < 0.005). CONCLUSION: Chronic obstructive pulmonary
      disease in Australian volunteers with no history of asthma encompasses many
      individuals with significant BDR. Interestingly, most volunteers reported ICS use
      and this was related to poorer spirometry and greater BDR. However, until the
      underlying immuno-pathology has been determined they cannot be assumed to have
      "asthma" or even an "asthmatic element".

PMID- 14656231
TI  - Audit of surgeon awareness of readmissions with venous thrombo-embolism.
AB  - AIM: An audit was undertaken to assess whether surgeons were informed of the
      readmission of their patients with postoperative deep venous thrombosis (DVT), or
      pulmonary embolus (PE). METHODS: A retrospective medical record review was
      conducted to detect patients who had an unplanned readmission in which DVT or PE
      formed part of the diagnosis and the first admission included a surgical
      procedure. The readmission was to John Hunter Hospital, Newcastle, Australia, a
      major tertiary referral teaching hospital, and the first admission was to any
      acute care hospital. The main outcome measures were: (i) hospital and specialty
      of the admitting doctor, (ii) the type of surgery performed, (iii) the length of
      time between admissions and (iv) the patient's previous medical history. The
      medical record was reviewed for documented evidence that the surgeon who
      performed the procedure was aware of the readmission. RESULTS: Of the 215 patient
      reviewed, 34 were classified as unplanned readmissions following a surgical
      procedure. Twenty-four patients (70.6%) were readmitted under a different
      specialty, three (8.8%) patients were readmitted under the same specialty but
      under a different surgeon, and seven (20.6%) patients were readmitted under the
      same surgeon. Of the 27 patients admitted under a different consultant, only 12
      (44.4%) had documented evidence that the previous surgeon was aware of the
      readmission. CONCLUSION: The rate of DVT/PE complications following surgery is
      underestimated. This may lead to a reduced emphasis in DVT/PE prophylaxis in the
      mistaken belief that DVT/PE frequency is rarer than it is. Improved communication
      between teams is necessary to improve care.

PMID- 14656232
TI  - Impact of an integrated approach to diabetes care at the Rumbalara Aboriginal
      Health Service.
AB  - AIMS: To describe the effectiveness of an integrated primary-secondary care
      diabetes clinic on metabolic control among indigenous patients in a rural
      community. METHODS: A retrospective audit of attendance to the clinic over 2
      years (2 August 1999 to 31 August 2001). The service included a weekly specialist
      diabetes clinic integrated with the primary care team at the Rumbalara Aboriginal
      Health Service, Mooroopna, Victoria, Australia. Between clinics, follow up was
      provided by the Aboriginal health worker and other members of the integrated care
      team. Of the 47 patients seen, 20 had an HbA1c persistently > or =9.0% (of 21
      patients identified in the community) and seven had gestational diabetes.
      RESULTS: Among 40 patients without gestational diabetes, microalbuminuria or
      proteinuria were present in 62%, retinopathy was present in 50%, neuropathy was
      present in 50% and at least one past cardiac or vascular event/surgical procedure
      had occurred in 25%. Of these, the 30 patients seen more than once increased
      their self glucose monitoring (baseline (53.3%) vs. last visit (90%); P = 0.003)
      and reduced their HbA1c (10.4 +/- 2.2%vs. 7.9 +/- 1.9%; P < 0.001), systolic
      blood pressure (138 +/- 20 vs. 127 +/- 18 mmHg; P = 0.003) and diastolic blood
      pressure (78 +/- 11 vs. 73 +/- 12 mmHg; P = 0.037) and total cholesterol (6.1 +/-
      1.7 vs. 5.1 +/- 1.6 mmol/L; P = 0.002), but not their weight, smoking or
      triglycerides. CONCLUSION: The introduction of an integrated diabetes care
      service in an Aboriginal health service can overcome many of the pre-existing
      barriers to achieving metabolic targets. Poor metabolic control in Aboriginal
      patients is often due to lack of resources and inappropriateness of approach,
      rather than "compliance".

PMID- 14656233
TI  - Advance directives and emergency department patients: ownership rates and
      perceptions of use.
AB  - BACKGROUND: Advance directives (ADs) are rarely available in Australia to guide
      management but may become more important as our population ages. AIMS: The
      present study aimed to determine patient knowledge, perception and ownership
      rates of ADs and the factors that impact upon these variables. METHODS: A cross
      sectional survey of emergency department patients was undertaken. The main
      outcome measures were: (i) prior discussion about the extent of medical treatment
      and ADs, (ii) knowledge and perceptions of ADs, (iii) present AD ownership rates
      and (iv) likelihood of future AD ownership. Generalized linear models were used
      for analysis. RESULTS: Four hundred and three patients were enrolled. The mean
      age of patients was 73 years and 239 (59.3%) were male. Two hundred and forty
      patients (59.6%) had discussed the extent of treatment. Only 81 patients (20.1%)
      had discussed the use of an AD. One hundred and thirty-seven patients (34.0%)
      knew of one type of AD and 333 patients (82.6%) thought some ADs were a good
      idea. Only 32 patients (7.9%) owned an AD, although 276 (68.5%) would consider
      owning one. The main reason for never obtaining an AD was "always wanting full
      treatment" (93 patients, 23.1%). Level of education was the only characteristic
      that impacted significantly upon an outcome measure. Patients with a higher level
      of education were more likely to have known and spoken about ADs, to own an AD
      and to consider owning one. CONCLUSIONS: AD knowledge and ownership rates were
      low. However, most patients perceive them favourably and many would consider
      owning one. Intervention strategies to improve AD awareness are indicated. This
      may empower patients to more effectively participate in their own advance care
      planning.

PMID- 14656234
TI  - Adults with cystic fibrosis: meeting the challenge!
AB  - The number of adults with cystic fibrosis (CF) is increasing. They are striving
      for independence and a fulfilling life with focus on career, relationships,
      education and finances at a time when lung function is likely to be declining and
      complications of this multi-system disease are increasing. Maintaining the
      quality and improving the duration of life are continuing challenges for the 
      clinician and the patient. Increased hope and greater expectations have been
      provided by a number of recent clinical advances and active research into novel
      treatments, including gene therapy. There has been increased recognition of the
      necessity for early diagnosis, adequate monitoring and effective intervention for
      complications such as diabetes and osteoporosis. Research into multi-resistant
      bacteria and clonal strains of Pseudomonas aeruginosa is ongoing and attention
      has focused on infection control policies. Although more high-level evidence is
      required on many issues confronting people with CF, a considerable effort has
      been made over the last decade to provide a more evidence-based approach to
      therapy with a number of large controlled clinical trials. For the adult with CF,
      there are also more decisions to be made. There is focus on reproductive health,
      with most couples enjoying the real possibility of having children. For those
      with advanced disease, the option for lung transplantation is well established.
      Maintenance of quality care will require adequate planning, effective transition
      programmes from paediatric to adult care, specialized training for doctors,
      nurses and allied health professionals and the allocation of sufficient resources
      to accommodate the inevitable increase in patient numbers.

PMID- 14656235
TI  - Diagnosis of primary hyperparathyroidism: controversies, practical issues and the
      need for Australian guidelines.
AB  - Primary hyperparathyroidism (PHPT) is one of the most common endocrine disease
      processes, however the clinical presentation in 2003 is typically characterized
      by minimal signs or symptoms of hypercalcaemia or para-thyroid hormone (PTH)
      excess. Recent developments in imaging and management of PHPT have been
      published, however the area of biochemical investigation has been relatively
      neglected. A group of experts convened in April 2002 to consider whether changes
      were needed to the 1990 consensus guidelines which defined criteria for the
      diagnosis and management of asymptomatic PHPT. It is appropriate to review the
      revised recommendations, which have been disseminated by the panel and were
      recently published. Each of the laboratory -analytes used to establish the
      diagnosis of PHPT and exclude alternative diagnoses or complications will be
      considered in succession in this review: (i) calcium, (ii) intact PTH, (iii)
      urinary calcium and (iv) 25 hydroxy-vitamin D. Furthermore, critical appraisal of
      the new diagnostic criteria and their applicability to Australian laboratories
      will be addressed. Finally, limitations and problems associated with the
      measurement of each analyte will be reviewed.

PMID- 14656236
TI  - Management of dyspepsia at the beginning of the twenty-first century.
AB  - Dyspepsia remains a frequent intercurrent management problem for the non
      gastroenterologist. However, the causes for dyspepsia have changed markedly in
      recent decades. In contrast to gastro-oesophageal reflux disease, both gastro
      oesophageal malignancy and peptic ulcer disease have become uncommon causes for
      dyspepsia. Concurrent with these changes, management strategies for dyspepsia
      have changed. Once aware of these changes the non-gastroenterologist can
      effectively manage the majority of patients with dyspepsia. The present paper
      reviews these key changes in dyspepsia management.

PMID- 14656237
TI  - The Sylvia and Charles Viertel Charitable Foundation: a decade of support for
      medical research in Australia.
AB  - The Sylvia and Charles Viertel Charitable Foundation
      (http://www.alfredresearch.org/external/viertel.htm) recently celebrated its
      first decade of support for medical research in Australia. Its contribution to
      Australian medical research has centred on support of outstanding young people
      through Senior Medical Research Fellowships and a unique grant-in-aid programme
      for clinical investigators.

PMID- 14656238
TI  - Diagnosis of malaria aided by polymerase chain reaction in two cases with low
      level parasitaemia.
AB  - Light microscopy of thick and thin blood smears is the mainstay of malaria
      diagnosis. In situations of low-level parasitaemia such as drug-modified disease,
      however, this may be difficult making clinical management problematic. Polymerase
      chain reaction (PCR) methods have shown high sensitivity for the diagnosis of
      malaria and are able to differentiate the Plasmodium species involved. Two cases
      are presented in the present study, which illustrate how a PCR method can aid
      light microscopic malaria diagnosis and species differentiation in returned
      travellers with low-level parasitaemia. Plasmodium vivax was detected by PCR
      prior to the light microscopy becoming positive in one case, and in the second
      case Plasmodium malariae was detected when light microscopy was unable to
      speciate the causative Plasmodium species.

PMID- 14656239
TI  - Oncogenic osteomalacia: culprit tumour detection whole body magnetic resonance
      imaging.

PMID- 14656240
TI  - Octreotide treatment of severe diabetic diarrhoea.

PMID- 14656241
TI  - Clopidogrel-associated acute arthritis.

PMID- 14656242
TI  - Mycobacterium tuberculosis infection following allogeneic peripheral blood stem
      cell transplantation.

PMID- 14656243
TI  - Blue fingers.

PMID- 14656244
TI  - Novel p53 germline mutation in a patient with Li-Fraumeni syndrome.

PMID- 14656245
TI  - Heparin nomograms: time for change.

PMID- 14656247
TI  - Treating legionnaires' disease.

PMID- 14656248
TI  - Live donor liver transplantation: where does it stand in Australia and New
      Zealand?

PMID- 14656249
TI  - Treatment and outcome of 104 hospitalized patients with legionnaires' disease.
AB  - BACKGROUND: Large outbreaks of Legionella pneumonia are rare, but when they occur
      provide an opportunity to assess predictors of mortality and efficacy of drug
      therapy. Although erythromycin has been the treatment of choice for many years,
      newer antimicrobials with increased activity against Legionella are available. A
      large outbreak of legionnaires' disease associated with the Melbourne Aquarium
      occurred in April 2000. AIM: To describe the patterns and impact of Legionella
      therapy, and predictors of outcome in a large group of hospitalized patients with
      legionnaires' disease. METHODS: A 6-month retrospective audit of hospitalized
      patients with proven legionnaires' disease around the time of the Melbourne
      Aquarium outbreak was conducted. Statistical analysis was performed using SAS
      version 8.0 (SAS Institute Inc., NC, USA). RESULTS: Data were obtained on 104
      patients (71 aquarium related, 33 not related). There were six deaths (mortality
      rate 5.8%), three of which were attributable directly to progressive
      legionnaires' disease. The major predictors of death were pre-existing cardiac
      failure (P = 0.0035) and renal disease (P = 0.026). Erythro-mycin is still the
      most commonly used antibiotic (80% received i.v. erythromycin) with clinicians
      prescribing more than one active Legionella drug in the majority of cases (76%).
      Choice of initial antibiotic therapy did not statistically affect outcome as
      measured by death, length of hospital stay or time to defervescence, although
      there was a trend towards improved survival with i.v. erythromycin (P = 0.063).
      Intravenous erythromycin was associated with a 19% rate of phlebitis, whereas
      side-effects from other antibiotics were uncommon. CONCLUSION: The most commonly
      used Legionella therapy in Australia remains erythromycin. This continues to be
      an effective agent, however, side-effects are common.

PMID- 14656250
TI  - Randomized, placebo-controlled trial of intramuscular vitamin B12 for the
      treatment of hyperhomocysteinaemia in dialysis patients.
AB  - BACKGROUND: Plasma homocysteine is elevated in patients with end-stage renal
      disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has
      been shown to partially reduce homocysteine levels in dialysis patients. It is
      not known whether vitamin B12 reduces homocysteine independent of folic acid in
      patients who are not vitamin B12 deficient. AIM: To determine whether 1 mg
      vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients
      independent of folic acid. METHODS: Twenty-eight haemodialysis patients were
      randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a
      double-blind fashion at 1-month intervals. Fasting plasma total homocysteine,
      folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined
      prior to each dose and 4 weeks after the final injection. The study was powered
      to detect a 30% reduction in homocysteine over the 3 months. RESULTS: Both the
      two groups were well matched with respect to total homocysteine levels, folic
      acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were
      significantly higher in the treatment group compared to placebo (217.7 pmol/L;
      95% confidence interval (CI) 103.0-332.5; P < 0.001) at the end of the trial but
      homocysteine levels were not significantly different (3.08 micromol/L; 95% CI 
      4.44-10.61; P= 0.406). CONCLUSIONS: The administration of intramuscular vitamin
      B12 over a 3-month period does not result in any reduction of plasma homocysteine
      levels in haemo-dialysis patients independent of folate status, however
      reductions of <30% cannot be excluded by the present study. High-dose folic acid
      remains the treatment of choice in reducing homocysteine, but whether this
      results in a reduction in cardiovascular events remains to be determined.

PMID- 14656251
TI  - Comparison of large- and small-bore intercostal catheters in the management of
      spontaneous pneumothorax.
AB  - BACKGROUND: Spontaneous pneumothoraces (SP) are a common cause of presentation to
      emergency departments and subsequent hospitalization. In recent years there has
      been an increasing trend towards the use of small-bore pleural catheters (PC)
      rather than conventional large-bore intercostal catheters (ICC) in their initial
      management. AIMS: To compare the effectiveness and complication rate of ICC and
      PC in the treatment of SP. METHODS: A retrospective chart audit was conducted of
      67 cases of SP admitted to the Royal Prince Alfred Hospital, Sydney, Australia,
      between 1 July 1997 and 30 June 2000. Demographic data were recorded, including:
      (i) patient age, (ii) smoking status, (iii) pneumothorax size, (iv) pneumothorax
      type and (v) aetiology. Outcome data relating to length of hospital stay (LOS)
      and treatment failure rates and complications of treatment devices were also
      recorded. RESULTS: Successful pneumothorax resolution was achieved (P = 0.72) in
      20 of the 31 (65%) patients initially treated with a ICC, and in 26 of the 36
      (72%) patients treated with a PC. The mean LOS in the ICC and PC group was 7 days
      and 5 days, respectively (P = 0.11). The complication rates in the PC and ICC
      group were 25% and 10%, respectively (P = 0.13), and the recurrence rates for
      each group were 17% and 6% (P = 0.20), respectively. However, the combined rate
      of complications and pneumothorax recurrence within 2 months was 42% in those
      initially treated with PC, compared with 16% in those treated with ICC (P =
      0.04). CONCLUSIONS: PC were as effective as ICC in treating SP in terms of
      initial pneumothorax resolution and LOS. There were trends towards higher
      complication and recurrence rates in those treated with PC, but individually
      these results did not reach statistical significance. However, the combined rate
      of complications and pneumo-thorax recurrence was significantly higher in those
      patients treated with the PC than in those treated with ICC.

PMID- 14656252
TI  - Outcome, tolerability and compliance of compassionate use interferon and
      ribavirin for hepatitis C infection in a shared care hospital clinic.
AB  - BACKGROUND AND AIMS: To determine response rate, side-effects and compliance in
      patients with chronic hepatitis C virus (HCV) infection following treatment with
      interferon-alpha-2b and ribavirin in a 'shared care' hospital clinic. METHODS:
      Data were collected prospectively on 81 patients treated with combination therapy
      for chronic HCV infection between 1999 and 2001. All had biochemical and
      virological evidence of active infection. All patients had undergone liver biopsy
      except haemophiliac patients. Patients infected with genotype 1 were treated for
      12 months. Patients infected with genotypes 2 and 3 were treated for 6 months.
      Patient care was shared with the referring general practitioner. Intention to
      treat, end of treatment and sustained virological response (SVR) rates, side
      effects and compliance were assessed. RESULTS: Eighty-one patients with chronic
      HCV infection were treated with combination therapy. The majority of HCV patients
      were genotype 1 (n = 46; 57%). There were 12 patients (15%) with cirrhosis. SVR
      rates were: (i) 24% for genotype 1, (ii) 58% for genotype 3 and (iii) 75% for
      genotype 2. SVR was achieved in three (23%) cirrhotic patients. Compliance with
      the treatment regimen was 98%. Seven per cent of patients were withdrawn from
      therapy prematurely because of side-effects. CONCLUSIONS: These 'shared care'
      clinic results compare well with controlled clinical trials using combination
      therapy for chronic HCV infection. Outcomes were poorer in genotype 1 patients
      and in patients with cirrhosis. Compliance with therapy was excellent because of
      the 'Shared Care Programme' with participation of general practitioners,
      psychiatrists and hepatitis C nurse practitioners in the management protocol.

PMID- 14656253
TI  - Secondary screening for osteoporosis in patients admitted with minimal-trauma
      fracture to a major teaching hospital.
AB  - AIMS: The aim of the present study was to determine: (i) the prevalence of the
      investigation and treatment of osteoporosis in patients admitted to hospital with
      a minimal-trauma fracture, (ii) the prevalence of osteoporosis using bone mineral
      density assessment by dual X-ray absorptiometry (DEXA) in such patients and (iii)
      a clinical pathway for the management of osteoporosis in such patients. METHODS:
      A cross-sectional study was undertaken involving all patients admitted with a
      fracture to Westmead Hospital, Sydney, Australia, between January 1999 and June
      2000 (n = 327). Of these, 264 were excluded because of: (i) the fracture
      following significant trauma (n = 83), (ii) unavailability of medical records for
      review (n = 38), (iii) nursing home status (n = 37), (iv) previous malignancy (n
      = 18), (v) deceased (n = 11), (vi) recent osteoporosis screening and/or treatment
      (n = 18), (vii) refusal to participate (n = 37), (viii) uncontactable (n = 16)
      and (ix) inadequate English (n = 6). The remaining 63 patients underwent DEXA
      assessment and the following laboratory investigations: (i) liver function tests,
      (ii) urea, (iii) electrolytes, (iv) calcium, (v) phosphate, (vi) full blood
      count, (v) 25-hydroxyvitamin D level and (vi) thyroid-function tests. In men,
      levels of serum free testosterone, luteinizing hormone, follicle-stimulating
      hormone and prolactin were also obtained. RESULTS: Of the 63 study participants,
      87% of the 47 women were either osteoporotic (T <-2.5) or osteopenic (-2.5 <T <
      1) at a mean of 12.7 +/- 5.4 months post-fracture. Of the 16 men screened, 75%
      had a T-score < or =-1. Forty-four per cent of the study sample had a low 25
      hydroxyvitamin D level, 6% were biochemically hyperthyroid and 40% of the men had
      a low serum free testosterone. Only 16% had an effective anti-osteoporotic
      medication added following the fracture. CONCLUSIONS: Secondary screening and
      treatment of osteoporosis in patients following minimal-trauma fracture are low.
      The implementation of a clinical pathway for osteoporosis management in these
      patients may be useful.

PMID- 14656254
TI  - The medical emergency team: does it really make a difference?
AB  - Hospital systems are failing the critically ill. This has been well documented in
      many countries around the world, with detailed reports of suboptimal care prior
      to intensive care and high rates of serious adverse events, including death.
      These events are potentially preventable, but insufficient attention has been
      directed towards developing solutions to these important problems to date. The
      medical emergency team (MET) is a system approach that promotes early and
      appropriate intervention in the care of critically ill hospital patients. The
      benefits of the MET in terms of absolute in-patient mortality and cardiac arrest
      rates are not yet well-defined, although preliminary studies are promising. The
      MET does provide a potentially beneficial impact on many other aspects of patient
      care. These benefits include: (i) facilitating an integrated and coordinated
      approach to patient care across the hospital, (ii) increasing awareness of at
      risk patients, (iii) encouraging early referral of seriously ill patients to
      clinicians with expertise in critical care and (iv) providing a foundation for
      quality initiatives for hospital-wide care of the seriously ill. The MET also
      empowers nursing staff and junior medical staff to call for immediate assistance
      in cases where they are seriously concerned about a patient, but may not have the
      experience, knowledge, confidence or skills necessary to manage them
      appropriately.

PMID- 14656255
TI  - New and emerging drug therapies for the management of acute heart failure.
AB  - In recent times, there have been many developments in therapies for acute heart
      failure, in contrast to the preceding 20 years. These have been mainly fueled by
      new and expanding knowledge about the pathophysiology of heart failure, which has
      allowed for insight into potential therapeutic strategies. This review will
      examine the key emerging therapies for acute heart failure, in light of available
      pathophysiological and clinical evidence.

PMID- 14656256
TI  - Hypertrophic cardiomyopathy: state-of-the-art review, with focus on the
      management of outflow obstruction.
AB  - Significant advances in our understanding and management of hypertrophic
      cardiomyopathy have been made in the last decade, as the complex genetics and
      phenotype-genotype correlations that characterize the disease are gradually
      unravelled. The well-described clinical heterogeneity of hypertrophic
      cardiomyopathy is now understood to be based on profound genetic variability,
      with at least 10 genes and over 150 mutations implicated. Several new therapeutic
      tools have entered clinical practice. The implantable cardioverter-defibrillator
      is now strongly indicated in those at high risk of sudden arrhythmic death. Our
      ability to abort sudden death in this subgroup has placed added emphasis on risk
      stratification in newly diagnosed patients. New procedures have also been
      developed for the relief of outflow obstruction in patients with refractory
      symptoms and a significant subaortic outflow gradient. Although not as
      efficacious as the 'gold-standard' surgical myectomy-myotomy, dual-chamber
      pacemaker implantation can be of modest benefit in select patients. Percutaneous
      transluminal septal myocardial ablation is an emerging catheter-based procedure
      for the relief of left ventricular outflow obstruction. Long-term follow-up data
      are still awaited. However, intermediate-term results suggest equivalent efficacy
      to surgical myectomy-myotomy.

PMID- 14656257
TI  - Embryonic stem-cell research and the moral status of embryos.
AB  - Stem-cell research has the potential to significantly advance our knowledge of
      cell differentiation with the promise of exciting and innovative therapeutic
      applications for otherwise incurable genetic and degenerative disorders. The
      issue has been the subject of debate in federal and state parliament as research
      of embryonic stem cells and their application have come under intense scrutiny.
      Scientists and medical practitioners are highly skilled in the technical aspects
      of biomedicine but are decidedly less comfortable with ethics. The place of novel
      and controversial biomedical technology is commonly left to an ad hoc and complex
      process whereby social acceptability eventually becomes the final arbiter.
      Utilitarianism is a popular ethical approach that attempts to weigh all the known
      and anticipated merits and pitfalls. The scientific background of biomedical
      professionals, the vast explosion of information, and specialization and
      subspecialization, have all contributed to a reductionistic view of life and
      ethics. The 'sanctity of life' doctrine is altogether quite different, as secular
      and religious advocates appear inflexible and unyielding to the logical
      propositions of utilitarianism and reductionism or to the consensus of democracy.
      These four major ethical approaches are discussed with reference to the embryonic
      stem-cell research debate.

PMID- 14656258
TI  - Ozbug: an email mailing list for physicians that works.
AB  - Very few studies of the quality of electronic mailing lists have been published.
      Ozbug was established in 1997 as a moderated and closed mailing list for
      infectious diseases physicians in Australia and New Zealand. A broad range of
      clinical and professional issues is discussed by -subscribers. An email survey of
      subscribers in 2002 indicated a high degree of satisfaction with the service.

PMID- 14656259
TI  - Lofgren syndrome in Turkey.
AB  - In the 36-year period between 1966 and 2002, 514 patients were diagnosed with
      sarcoidosis at Cerrahpasa Medical Faculty, Istanbul, Turkey, and of these 98
      (19.1%) had Lofgren syndrome. The frequency of female patients with Lofgren was
      higher than the frequency among other sarcoidosis patients (female:male ratio 4.8
      vs. 1.64; P < 0.001). Erythema nodosum was diagnosed in 72.4% of the subjects and
      arthritis or arthralgia was diagnosed in 51%. Erythema nodosum and arthritis or
      arthralgia were more frequent in Lofgren; however, pulmonary parenchymal
      involvement was more frequent in other sarcoidosis patients (all P-values <
      0.001).

PMID- 14656260
TI  - Reduction of medical error at the point-of-care using electronic clinical
      information delivery.
AB  - There is accumulating evidence that point-of-care delivery of clinical
      information such as evidence-based medicine, practice guidelines and drug
      information can streamline clinical practice and reduce preventable errors. In
      Australia, hospital-based physicians have -generally been slow to fully use these
      resources to enhance their clinical practice. Here we provide an introduction to
      the practical application of several hand-held and electronic information systems
      available to Australian physicians.

PMID- 14656261
TI  - Congenital obstructive mitral-valve aneurysm.

PMID- 14656262
TI  - Use of endovascular metal stents to alleviate malignant superior vena cava
      syndrome.

PMID- 14656263
TI  - Anti-CD20 monoclonal antibody (rituximab) therapy in a child with refractory
      chronic autoimmune haemolytic anaemia.

PMID- 14656264
TI  - Physiological altitude and high-altitude pulmonary oedema.

PMID- 14656265
TI  - Carrion's disease: an altitude-associated infectious disease.

PMID- 14656266
TI  - Utility of medical ethics.

PMID- 14656267
TI  - A high proportion of patients with ST elevation myocardial infarction do not come
      to hospital by ambulance.

PMID- 14656269
TI  - Proteomic analysis for early detection of ovarian cancer: a realistic approach?
AB  - Ovarian cancer is a multifaceted disease wherein most women are diagnosed with
      advanced stage disease. One of the most imperative issues in ovarian cancer is
      early detection. Biomarkers that allow cancer detection at stage I, a time when
      the disease is amenable to surgical and chemotherapeutic cure in over 90% of
      patients, can dramatically alter the horizon for women with this disease. Recent
      developments in mass spectroscopy and protein chip technology coupled with
      bioinformatics have been applied to biomarker discovery. The complexity of the
      proteome is a rich resource from which the patterns can be gleaned; the pattern
      rather than its component parts is the diagnostic. Serum is a key source of
      putative protein biomarkers, and, by its nature, can reflect organ-confined
      events. Pioneering use of mass spectroscopy coupled with bioinformatics has been
      demonstrated as being capable of distinguishing serum protein pattern signatures
      of ovarian cancer in patients with early- and late-stage disease. This is a
      sensitive, precise, and promising tool for which further validation is needed to
      confirm that ovarian cancer serum protein signature patterns can be a robust
      biomarker approach for ovarian cancer diagnosis, yielding improved patient
      outcome and reducing the death and suffering from ovarian cancer.

PMID- 14656270
TI  - What have we learned from ICON1 and ACTION?
AB  - Still, 20-30% of women with early-stage ovarian cancer eventually die from their
      disease. Adequate treatment for this subset of patients has not yet been
      identified, the greatest dispute being about the role of adjuvant therapy after
      surgical staging. No randomized trial has reliably demonstrated a survival
      advantage for one of the many approaches over another or over careful observation
      without immediate further adjuvant therapy. A combined analysis of two parallel
      randomized clinical trials in early ovarian cancer, ICON 1 and ACTION, comparing
      platinum-containing adjuvant chemotherapy to observation following surgery was
      performed, with survival as primary end point and time to recurrence as a
      secondary one. A total of 924 patients were randomized. With over 4 years median
      follow up for survivors, the hazard ratio for recurrence-free survival is 0.64
      (95% CI, 0.50-0.82; P = 0.001) in favor of adjuvant chemotherapy, with an
      absolute difference of 11%. For overall survival, the hazard ratio is 0.67 (95%
      CI, 0.50-0.90; P = 0.008) in favor of adjuvant chemotherapy. These results
      translate into an absolute difference of 8% in the adjuvant chemotherapy group
      and indicate that adjuvant platinum-containing chemotherapy improves the survival
      and disease-free survival. Sub-group analysis demonstrated in the ACTION trial
      that completeness of surgical staging was an independent factor for prognosis,
      both for progression-free and for overall survival (along with histological type
      and tumor grade), while in suboptimally staged patients, adjuvant chemotherapy
      did improve the outcome.

PMID- 14656271
TI  - Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin
      regimen over the cyclophosphamide-cisplatin combination in advanced ovarian
      cancer.
AB  - Two independent and consecutive randomized clinical trials, conducted by the
      American Gynecological Oncology Group and by an European-Canadian Intergroup,
      have shown superiority, in clinical response rate, progression-free survival, and
      overall survival, of a cisplatin-paclitaxel regimen over cisplatin
      cyclophosphamide given as first-line chemotherapy for women with advanced
      epithelial ovarian cancer. The results of these studies, published with a median
      follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each
      case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this
      advantage remains both statistically and clinically significant and supports a
      role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

PMID- 14656272
TI  - Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel versus
      cisplatin and paclitaxel (GOG158) and an update on GOG0182-ICON5.
AB  - Mature results from GOG158 have clearly established carboplatin and paclitaxel as
      an effective and well-tolerated standard regimen, providing a basis for the
      reference arm in GOG0182-ICON5, an ongoing multiarmed phase III trial of the
      Gynecologic Cancer InterGroup (GCIG) evaluating the incorporation of newer
      cytotoxic agents. Results from GOG158 will be reviewed, including an analysis of
      second-look surgical outcomes, followed by an update on the current status of
      GOG0182-ICON5.

PMID- 14656273
TI  - Sequential single agents as first-line chemotherapy for ovarian cancer: a
      strategy derived from the results of GOG-132.
AB  - First-line chemotherapy for ovarian cancer during the past decade has evolved
      toward the use of carboplatin and paclitaxel combinations. This has been based on
      randomized trials showing that combinations of these two drugs lead to a outcome
      similar to that obtained using cisplatin and paclitaxel (that had, in turn,
      proven superior in progression-free survival and overall survival to cisplatin
      and cyclophosphamide) but with less toxicity. Surprisingly, taxane-platinum
      combinations were not superior to control arms in two studies (ICON3 and GOG-132)
      utilizing carboplatin or cisplatin as the comparators. This has renewed interest
      in the role of single agents in first-line chemotherapy - a concept also
      supported by a number of prior clinical trials with single-agent platinum
      compounds yielding results not inferior to combinations. Early 'pre-emptive'
      crossover (prior to the stipulated clinical progression) to paclitaxel or a
      paclitaxel-containing regimen, however, occurred in 24% of patients initially
      treated with cisplatin on GOG-132. This has led to the interpretation of this
      trial as a combination versus sequential design. Although not subscribing to this
      interpretation, the results of GOG-132 and ICON3 not only raise doubts over a
      clear superiority of combinations over single agents but also lead to a
      consideration of sequential treatment designs for first line. Advantages of such
      designs are: (a) ability to provide 'dose-dense' platinums followed by 'dose
      dense' paclitaxel and, perhaps, other drugs; and (b) the potential of acquiring
      biological data linked to the antitumor effects of a specific drug. Mathematical
      modeling and recent positive results in breast cancer adjuvant therapy support
      the use of 'dose-dense' strategies, and these should be considered in the design
      of future trials in ovarian cancer.

PMID- 14656274
TI  - The potential role of neoadjuvant chemotherapy in advanced ovarian cancer.
AB  - There is a multitude of evidence from retrospective analyses and meta-analyses
      showing that the amount of residual tumor after debulking surgery and before
      chemotherapy is one of the most powerful prognostic determinants in advanced
      ovarian cancer. This supports the important role of maximum cytoreductive surgery
      as one of the cornerstones in the treatment of this disease. These same analyses,
      however, do not suggest that patients whose tumors cannot be debulked optimally
      derive a significant survival benefit from upfront surgery. For these patients
      and those who have a poor performance status or other morbidity, making
      comprehensive upfront surgery contraindicated, different therapeutic approaches
      have to be explored. One possible way to go is to change the timing of the
      different therapeutic modalities: upfront chemical cytoreduction, followed by a
      maximal surgical effort, in turn followed by the remainder of the first-line
      chemotherapy or neoadjuvant chemotherapy and interval or delayed debulking
      surgery. The potential role of this approach and the experience with it thus far
      are discussed.

PMID- 14656275
TI  - Improving first-line therapy of advanced ovarian cancer - the AGO Ovarian Cancer
      Study Group perspective.
AB  - This review displays the AGO Ovarian Cancer Study Group approach towards
      evaluation of improvement options in first-line therapy of advanced ovarian
      cancer. Prospectively randomized phase III trials evaluating the addition of
      newer drugs to standards carboplatin-paclitaxol (TC) as well as pilot trials
      evaluating new treatment modalities like anti-idiotype CA 125 antibodies or
      epidermal growth factor receptor (EGFR) modulation are presented.

PMID- 14656276
TI  - First-line treatment of ovarian cancer FIGO stages IIb-IV with
      paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin.
AB  - The objective of this study was to compare the safety and efficacy of carboplatin
      plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the
      treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March
      1999 and August 2001, 887 patients were randomized to receive six to nine cycles
      of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5,
      Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to
      paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free
      survival. Demographic information: Residual disease <1 cm was reported on 41% of
      patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had
      achieved a clinical complete response, and 18 and 25% a clinical partial response
      resulting in an overall response rate of 83% in the TEC and 80% in the TC arm,
      whereas 7 and 9% had progressive disease, respectively. The three-drug
      combination produced a markedly higher myelotoxicity, resulting in a higher
      frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients)
      and a higher number of dose reductions and treatment delays. Cycle prolongation
      above seven days was seen in 7 and 5% of cycles in the TEC and TC arm,
      respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5%
      TC). Reductions in left ventricular ejection fraction of more than 15% after six
      courses were slightly more common with the TEC regimen (3% versus 1.5%), but the
      difference was not statistically significant (P = 0.2). In conclusion, treatment
      with the TEC combination produced a higher rate of complete responses than
      treatment with the TC combination. Toxicity was manageable. Long-term survival
      data are awaited.

PMID- 14656277
TI  - The role of anthracyclines in second-line therapy of ovarian cancer.
AB  - Anthracyclines (ANTs) have been in clinical practice since the 1960s and
      represent one of the most commonly used classes of anticancer drugs. In the
      1990s, meta-analyses showed a favorable impact of doxorubicin (DOX/A) on the
      survival of patients with advanced ovarian cancer, when it was combined with
      cyclophosphamide and cisplatin (CAP) and compared to CP alone. With the
      acceptance of paclitaxel-carboplatin (TCb) as the new reference arm for first
      line treatment, testing the addition of ANTs to TCb seems a logic next step.
      Trials presently testing this, make use of either epirubicin (EPI) or pegylated
      liposomal doxorubicin (PLD: Doxil(R)/Caelyx(R)). These are the two most favorable
      ANTs, based on data obtained with various ANTs in ovarian cancer failing platinum
      based chemotherapy. EPI has not been evaluated in direct comparison with other
      antineoplastic agents. PLD has been compared with both paclitaxel and topotecan.
      No difference in efficacy parameters could be observed, but the toxicity profile
      of PLD scored favorably against those of the comparator in both trials, despite
      the fact that palmar-plantar erythrodysesthesia can be troublesome, and sometimes
      lead to treatment discontinuation. Data from four randomized trials evaluating
      the role of ANT combinations in patients with relapsed ovarian cancer suggest
      that the addition of EPI or DOX to paclitaxel does not lead to better outcomes in
      patients with platinum- refractory or resistant disease. In platinum-sensitive
      disease, any benefit of EPI-platinum or DOX-platinum combinations over platinum
      alone is uncertain. There are no randomized trials with PLD combinations in the
      second-line setting. It is concluded that both EPI and PLD can be recommended as
      a reasonable single-agent treatment option for relapsed patients, with a
      preference for PLD taking into account its more favorable toxicity profile.

PMID- 14656278
TI  - Is combination chemotherapy superior to single-agent chemotherapy in second-line
      treatment?
AB  - Treatment of relapsed ovarian carcinoma is still a matter of controversy. One
      important question to be solved is the potential superiority of combination
      chemotherapy over single-agent chemotherapy. This is a field in which a
      nonconclusive small number of randomized clinical trials have been conducted, and
      therefore, definitive conclusions are lacking. Patients with recurrent platinum
      resistant disease are better treated with sequential single agent, because of
      higher toxicity without clear benefit usually associated with combination
      chemotherapy. In patients with platinum-sensitive disease, we can choose between
      three options: single-agent carboplatin, single-agent new drug or platinum
      combination-based therapy. In this paper, we will review these options and
      recently closed or ongoing randomized clinical trials in this setting.

PMID- 14656279
TI  - Consolidation treatment of advanced ovarian carcinoma with radiotherapy after
      induction chemotherapy.
AB  - In a prospective randomized trial, consolidation treatment with radiotherapy or
      chemotherapy was compared with no treatment in a series of 172 patients with
      epithelial ovarian carcinoma, FIGO stage III, with complete surgical remission
      after primary cytoreductive surgery and induction chemotherapy. In the subgroup
      with complete pathological remission, progression-free survival (PFS) was
      significantly (P = 0.032) better in the radiotherapy group (56%) than in the
      chemotherapy group (36%) and the untreated control group (35%). The number of
      recurrences was lowest in the radiotherapy group. The overall relapse rate was
      reduced by 33% and the pelvic recurrences by 43% by consolidation radiotherapy.
      On the other hand, treatment-related side effects were more frequent in the
      radiotherapy group.

PMID- 14656280
TI  - Intraperitoneal cisplatin versus no further treatment: 8-year results of EORTC
      55875, a randomized phase III study in ovarian cancer patients with a
      pathologically complete remission after platinum-based intravenous chemotherapy.
AB  - First-line intravenous chemotherapy (CT) following debulking surgery is
      associated with prolonged survival, in particular in patients who achieve a
      pathological complete remission (pCR) at second-look surgery but in whom a high
      rate of relapses still occurs. Between 1988 and 1997, 153 patients in pCR
      following platinum-based intravenous CT were randomized between four courses of
      intraperitoneal cisplatin (P) (90 mg/m2 every 3 weeks) or observation. Overall
      survival (OS) was the primary endpoint, while progression-free survival (PFS) was
      a secondary endpoint. This intent-to-treat analysis includes 16 patients who were
      not eligible and 17 patients who had protocol violations. The two groups were
      well balanced in terms of age (median = 55 years), performance status (78% P.S.
      O), FIGO stage (96% stage III), histology (serous in 66%), grade (2 or 3 in 80%),
      and residuum before intravenous CT (>1 cm in 40%). Intraperitoneal CT was
      delivered mainly through intraperitoneal catheters (Port-a-Cath 61% and Tenckhoff
      25%). Side effects of intraperitoneal cisplatin included vomiting [> or =grade 2
      (82%)], rise in serum creatinine [> or =grade 2 (14%)], abdominal pain [grade 1-2
      (38%)], and neurotoxicity [grade 2-3 (15%)]. After a median follow-up of 8 years,
      80 patients (52%) have progressed with no difference in the pattern of relapse
      between the two groups and 75 patients (49%) have died; the respective hazard
      ratios for PFS and OS with 95% CI are 0.89 (0.59-1.33) and 0.82 (0.52-1.29).
      These results are suggestive of a treatment benefit but do not support a change
      in clinical practice. Other randomized clinical trials of intraperitoneal CT are
      reviewed and briefly discussed.

PMID- 14656281
TI  - Consolidation therapy revisited: intravenous chemotherapy.
AB  - The administration of 'consolidation' therapy is designed to maximize the
      benefits achieved from primary chemotherapy, to both improve progression-free and
      overall survival. Paclitaxel is an excellent agent to consider for a
      consolidation strategy in ovarian cancer, based on its activity in the disease,
      its cycle-specificity, and the lack of serious cumulative toxicity (except for
      neuropathy). A recently reported randomized trial conducted by the South-west
      Oncology Group and the Gynecologic Oncology Group revealed that 12-monthly cycles
      of single-agent paclitaxel (175 mg/m2 over 3 h) improves progression-free
      survival (PFS), compared to 3-monthly cycles of the agent (median PFS: 28 months
      versus 21 months, P = 0.0023, and hazard ratio 2.31). Further exploration of
      consolidation/maintenance therapy in the management of ovarian cancer is
      indicated, focusing on agents that are easy to administer (eg, oral) and that
      result in limited cumulative toxicity.

PMID- 14656282
TI  - Consolidation therapies revisited: weekly paclitaxel.
AB  - Most patients with advanced ovarian cancer exhibit clinically relevant objective
      and subjective responses to platinum/paclitaxel-based combination, which is now
      considered the standard chemotherapeutic regimen. Unfortunately, responses are
      generally of limited duration, and long-term disease-free survival is experienced
      by few patients. Efforts should be taken to maintain such a response as long as
      possible, where it realistically might be hoped that continuation of chemotherapy
      could consolidate the absence of clinically detectable disease. In this regard,
      the administration of paclitaxel on a weekly schedule seems to be particularly
      attractive, especially after the demonstration that a weekly regimen in heavily
      pretreated women bearing metastatic breast, head, and neck or lung cancers was
      proven to be well tolerated without the requirement of granulocyte colony
      stimulating factors, with limited neurotoxicity and with substantial anticancer
      activity, thanks to its pro-apoptotic and antiangiogenesis properties. In Italy,
      a multi-institutional phase II prospective study (After-6 Protocol 2) has been
      initiated to verify the effectiveness of paclitaxel, administered on a weekly
      schedule (60 mg/m2 for 21 courses), in patients bearing microscopic residual
      disease detected at second-look operation to define its effectiveness after
      completing their primary platinum/paclitaxel chemotherapy treatment. When
      possible, patients were surgically re-evaluated thorough a third-look operation
      to evaluate the percentage of conversion of microPR into a pathological complete
      remission status. An interim evaluation based on 534 cycles administered to 41
      patients showed than only one patient experienced grade 4 anemia, 7.4% grade 2
      transient peripheral neurotoxicity, and 2.7% delay in treatment delivery.
      Therefore, weekly paclitaxel has been proven to be easily administered even in
      heavily pretreated patients, with acceptable hematological and neurological
      toxicity.

PMID- 14656283
TI  - Cost-effectiveness studies in ovarian cancer.
AB  - Ovarian cancer is the fifth leading cause of cancer-related deaths. The costs
      associated with this cancer impact both on the affected individual and on the
      health system. Screening is currently unproven as a strategy for improving
      outcomes for women with ovarian cancer. Randomized controlled trials, however,
      are underway, estimating any impact of screening with ultrasound and CA125 on
      ovarian cancer mortality. Paclitaxel and carboplatin combination, the standard
      first-line chemotherapy regimen for ovarian cancer, has not been compared with
      cisplatin and cyclophosphamide regarding the cost-effectiveness and cost-utility,
      but for paclitaxel and cisplatin, numerous studies have addressed these issues.
      The estimated incremental costs resulting from these studies fall well within the
      generally accepted range for new therapies. Although acquisition costs of new
      chemotherapy drugs exceed those of older drugs, the impact of costly drugs on
      total costs may be cost saving due to less costs related to supportive and
      palliative care. The most important costs for the patient, the pain and suffering
      associated with ovarian cancer and its treatment, are hard to quantify.
      Nevertheless, patients' quality of life must be considered when making a clinical
      decision to treat this disease. A review of available cost-effectiveness studies
      is presented and discussed.

PMID- 14656284
TI  - Translational research in ovarian cancer: a must.
AB  - Ovarian cancer discovered at late clinical stage continues to be a fatal disease.
      It seems self-evident that if we are to make an impact on the survival of
      advanced ovarian cancer patients, we must begin to understand the disease more
      completely. This should improve the diagnosis of the disease at an early stage
      when it is curable by surgery or develop better/targeted drug treatments. Modern
      molecular techniques have provided insights into many of the molecular changes
      that occur when ovarian cancer develops, but one must understand that changes
      seen in this way can only be said to correlate with disease. It would be helpful
      to have a way to test candidate changes for causality. In many cancer types,
      genetically engineered animals are beginning to be used for this purpose and as a
      means to study the disease process in greater detail. To date, there has been no
      way to study ovarian cancer by this means. Efforts to model human ovarian cancer
      have been delayed by a general lack of understanding both of the disease process
      in humans and of the cells widely believed to be the precursors of epithelial
      ovarian cancer, the ovarian surface epithelial (OSE) cells. Here, we present
      recent progress in modeling ovarian cancer using genetically modified mice.

PMID- 14656285
TI  - Systemic treatment policies in ovarian cancer: the next 10 years.
AB  - Over the past two decades, the development of treatment policies and practice
      standards has become formalized. In ovarian cancer, most attention has been
      focused on the development of policies for front-line systemic treatment, using
      survival as the major outcome that should drive change. This review summarizes
      the evidence that supported the emergence of paclitaxel-carboplatin as a widely
      used standard of care for front-line therapy and some of the contradictory data
      from randomized studies. Furthermore, recently completed or ongoing randomized
      studies of the addition of a third cytotoxic agent to paclitaxel-carboplatin are
      summarized. Finally, some novel noncytotoxic approaches are discussed. New
      standards of care and treatment policies in the next decade will be based on high
      quality evidence of improved survival from controlled studies. Many such trials
      are now ongoing or planned.

PMID- 14656286
TI  - Ovarian cancer treatment: what is new.
AB  - Ovarian cancer is still the fourth cause of death by cancer among women and the
      most fatal among gynecological tumors. The purpose of this symposium is, year
      after year, to report and discuss the new developments in the treatment of
      patients with ovarian cancer, the majority of whom still present with advanced
      disease. It also tries to make it clear to the participants what is evidence
      based and what is not. Mature data of both classic studies like GOG-111, OV-10,
      and more recent studies like GOG-158, AGO-OVAR-3, and the intergroup
      paclitaxel/epirubicin/carboplatin (TEC) versus paclitaxel/carboplatin (TC) study
      have been presented. Other current controversial issues included in this edition
      were sequential single-agent versus simultaneous administration of combination
      chemotherapy, the role of combination chemotherapy in second-line treatment, the
      role of consolidation therapy, the role of anthracyclines in the treatment, and
      cost-effectiviness studies in ovarian cancer. Although the main topic of the
      symposium is advanced disease, this edition included the results of two parallel
      randomized studies (ACTION and ICON1) on the treatment of early disease. In
      addition, new trends in early detection of ovarian cancer have been updated. The
      pace of new agent development has increased, and it would be helpful to have more
      efficient preclinical models and early phase-clinical trials to guide the
      selection of active agents for phase III evaluation. Reaching international
      consensus is a challenge but offers the opportunity to test multiple regimens
      more efficiently against a single-control population, rather than conducting
      multiple smaller studies with redundant internal controls. If indeed answers to
      the relevant questions are to be obtained more quickly, then, a network of
      current national or international groups could potentially facilitate this.

PMID- 14656287
TI  - 5-HT inhibits N-type but not L-type Ca(2+) channels via 5-HT1A receptors in
      lamprey spinal neurons.
AB  - 5-HT is a potent modulator of locomotor activity in vertebrates. In the lamprey,
      5-HT dramatically slows fictive swimming. At the neuronal level it reduces the
      postspike slow afterhyperpolarization (sAHP), which is due to apamin-sensitive
      Ca(2+)-dependent K+ channels (KCa). Indirect evidence in early experiments
      suggested that the sAHP reduction results from a direct action of 5-HT on KCa
      channels rather than an effect on the Ca(2+) entry during the action potential.
      In view of the characterization of different subtypes of Ca(2+) channels with
      very different properties, we now reinvestigate if there is a selective action of
      5-HT on a Ca(2+) channel subtype in dissociated spinal neurons in culture. 5-HT
      reduced Ca(2+) currents from high voltage activated channels. N-type, but not L
      type, Ca(2+) channel blockers abolished this 5-HT-induced reduction. It was also
      confirmed that 5-HT depresses Ca(2+) currents in neurons, including motoneurons,
      in the intact spinal cord. 8-OH-DPAT, a 5-HT1A receptor agonist, also inhibited
      Ca(2+) currents in dissociated neurons. After incubation in pertussis toxin, to
      block Gi/o proteins, 5-HT did not reduce Ca(2+) currents, further indicating that
      the effect is caused by an activation of 5-HT1A receptors. As N-type, but not L
      type, Ca(2+) channels are known to mediate the activation of KCa channels and
      presynaptic transmitter release at lamprey synapses, the effects of 5-HT reported
      here can contribute to a reduction in both actions.

PMID- 14656288
TI  - The immunocytochemical localization of connexin 36 at rod and cone gap junctions
      in the guinea pig retina.
AB  - Connexin 36 (Cx36) is a channel-forming protein found in the membranes of apposed
      cells, forming the hexameric hemichannels of intercellular gap junction channels.
      It localizes to certain neurons in various regions of the brain including the
      retina. We characterized the expression pattern of neuronal Cx36 in the guinea
      pig retina by immunocytochemistry using specific antisera against Cx36 and
      green/red cone opsin or recoverin. Strong Cx36 immunoreactivity was visible in
      the ON sublamina of the inner plexiform layer and in the outer plexiform layer,
      as punctate labelling patterns. Double-labelling experiments with antibody
      directed against Cx36 and green/red cone opsin or recoverin showed that strong
      clustered Cx36 immunoreactivity localized to the axon terminals of cone or close
      to rod photoreceptors. By electron microscopy, Cx36 immunoreactivity was visible
      in the gap junctions as well as in the cytoplasmic matrices of both sides of cone
      photoreceptors. In the gap junctions between cone and rod photoreceptors, Cx36
      immunoreactivity was only visible in the cytoplasmic matrices of cone
      photoreceptors. These results clearly indicate that Cx36 forms homologous gap
      junctions between neighbouring cone photoreceptors, and forms heterologous gap
      junctions between cone and rod photoreceptors in guinea pig retina. This focal
      location of Cx36 at the terminals of the photoreceptor suggests that rod
      photoreceptors can transmit rod signals to the pedicle of a neighbouring cone
      photoreceptor via Cx36, and that the cone in turn signals to corresponding
      ganglion cells via ON and OFF cone bipolar cells.

PMID- 14656289
TI  - Two variants of the rat brain sodium-driven chloride bicarbonate exchanger
      (NCBE): developmental expression and addition of a PDZ motif.
AB  - Regulation of pH in the central nervous system is critical to normal brain
      function and response to pathophysiological conditions. Here we identify two
      novel variants of the sodium-driven chloride bicarbonate exchanger (NCBE) from
      brain. The developmental expression pattern seen by in situ hybridization for the
      90-bp containing insert (insert A) reveals strong expression in spinal cord and
      brain beginning in embryonic development. High-level expression is seen in
      cerebellar Purkinje cells and principal cells in hippocampus. The variant missing
      a 39-bp insert at the 3' end (insert B) encodes a protein in which the deduced
      carboxyterminal three amino acids are replaced with a unique 21 amino acid
      stretch terminating in a PDZ motif. rb2NCBE, the PDZ motif-encoding variant, is
      more highly expressed in astrocytes than is rb1NCBE. Both variants are expressed
      at similar levels in neurons. Expression varies with age and cell type. The FLAG
      epitope was fused in-frame at the amino terminus and each variant was expressed
      using a retroviral vector to study subcellular localization. Both variants were
      associated with the plasma membrane, but rb2NCBE colocalized with actin filaments
      to a greater extent, suggesting the PDZ form may interact with the cytoskeleton,
      whereas rb1NCBE was more often seen in intracellular vesicles. The PDZ motif
      containing variant was much more active in pH regulation, with the expected ionic
      dependence on Na+, HCO3- and Cl- when expressed in 3T3 cells. These results are a
      first step towards understanding the regulation of expression and activity of
      this transporter in the brain.

PMID- 14656290
TI  - Rapid activation of presynaptic nicotinic acetylcholine receptors by nerve
      released transmitter.
AB  - Nicotine's ability to enhance neurotransmitter release has implicated presynaptic
      nicotinic acetylcholine receptors (nAChRs) in synaptic modulation, but there aze
      few examples where presynaptic nAChRs are known to be activated by nerve-released
      transmitter. We searched for endogenous activation of presynaptic nAChRs in the
      calyceal nerve terminals of the chick ciliary ganglion by imaging presynaptic
      calcium transients using dextran-coupled indicator dyes. The amplitude of
      Ca(+)signals recorded in individual nerve terminals was frequency dependent over
      2-50 Hz. Calcium transients evoked by stimulation of the preganglionic nerve were
      significantly reduced (approximately 10-15%) by the nonspecific nAChR antagonist
      d-tubocurarine (d-TC; 100 microM) and the alpha7-specific antagonist
      methyllycaconitine (20-50 nM) but were not affected by 10 microM dihydro-beta
      erythroidine, which should inhibit several non-alpha7 nAChRs. Feedback was rapid
      and did not require a stimulation-dependent build-up of transmitter, as d-TC and
      MLA reduced the amplitude of the first calcium transient in a 2-Hz train. Choline
      is an agonist at alpha7 nAChRs but is not the sole agonist in this system, as
      inhibition of acetylcholinesterase by echothiophate failed to reduce calcium
      transients. These results show that nerve-released acetylcholine (ACh) feeds back
      onto presynaptic alpha7 nAChRs to enhance calcium signals within the terminal.
      This feedback may help maintain the high rate of transmission at this cholinergic
      synapse.

PMID- 14656291
TI  - Galanin increases membrane excitability and enhances Ca(2+) currents in adult,
      acutely dissociated dorsal root ganglion neurons.
AB  - We examined the effect of galanin (10(-15) - 10(-7) M) on dispersed, mainly small
      sized dorsal root ganglion (DRG) neurons in adult rats using whole-cell patch
      clamp. Galanin and AR-M1896, a selective galanin type 2 receptor (GalR2) agonist,
      both significantly increased the number of action potentials in response to
      current pulses in 77% of the neurons, indicating an increase in excitability.
      Galanin also caused a rise in input resistance, decreased the holding current for
      -60 mV and depolarized the resting potential. In addition, Ca(2+) currents
      elicited by voltage steps were significantly increased by both galanin and AR
      M1896 in nearly 70% of the cells. This enhancement was observed in 30% of the
      neurons in the presence of nimodipine or omega-conotoxin, but in each case
      approximately 60% less than without blocking either N- or L-type Ca(2+) channels,
      indicating modulation of both types of Ca(2+) channels. The percentage of small-
      and medium-sized neurons expressing GalR2 mRNA in DRGs in situ was similar to
      that showing increased excitability and Ca(2+) current after galanin application,
      i.e. approximately 70-80% of the neurons. The findings suggest that GalR2 has a
      role in controlling both the excitability, probably by inhibition of GIRK or leak
      K(+) channels, and Ca(2+) entry in a large population of presumably nociceptive
      neurons. The combination of the two effects, which possibly arise from separate
      biochemical pathways, would increase excitability and enhance intracellular
      Ca(2+) signalling which would enhance sensory transmission. These mechanisms
      involving GalR2 receptors may underlie the pronociceptive effects of galanin
      described in the literature.

PMID- 14656292
TI  - Dopamine receptor supersensitivity in rat subthalamus after 6-hydroxydopamine
      lesions.
AB  - The subthalamic nucleus (STN) receives direct dopaminergic innervation from the
      substantia nigra pars compacta, but the importance of this input in the
      pathophysiology of parkinsonism remains to be determined. We used whole-cell
      patch-clamp recordings in brain slices to study presynaptic dopaminergic
      modulation of synaptic inputs to the STN in unilateral 6-hydroxydopamine (6-OHDA)
      lesioned rats. Here, we report that dopamine was more potent for inhibiting GABA
      IPSCs and glutamate EPSCs in the STN ipsilateral to the lesion, and was less
      potent for suppressing IPSCs and EPSCs in the STN contralateral to the lesion,
      compared with the effects of dopamine in control STN. Dopamine reduced IPSCs with
      an IC50 value of 20.9 +/- 3.6 microM in control STN, whereas IC50 values were
      0.83 +/- 0.15 and 55.1 +/- 11.1 microM in STN ipsilateral and contralateral to 6
      OHDA lesions, respectively. Dopamine also inhibited EPSCs with an IC50 value of
      12.8 +/- 2.8 microM in control STN, whereas IC50 values were 4.5 +/- 0.9 and 41.6
      +/- 9.8 microM in STN ipsilateral and contralateral to 6-OHDA lesions,
      respectively. Results with paired stimuli to evoke EPSCs and IPSCs suggest that
      endogenous dopamine acts presynaptically to inhibit transmitter release in the
      STN. These results show that chronic dopamine denervation significantly alters
      the regulation of synaptic input to the STN. Our results also suggest that the
      STN may be an important target for levodopa therapy in Parkinson's disease.

PMID- 14656293
TI  - Active release of glycine or D-serine saturates the glycine site of NMDA
      receptors at the cerebellar mossy fibre to granule cell synapse.
AB  - The current and calcium influx generated by NMDA receptors depend on the
      concentration of the coagonist glycine, or its analogue d-serine, in the synaptic
      cleft. If there is no release of glycine, the ionic stoichiometry of the glial
      GlyT1 glycine transporters expressed near NMDA receptors in the brain should be
      able to lower the extracellular glycine concentration to below the EC50 for
      coactivation of NMDA receptors. We examined whether changing the glycine or d
      serine concentration in the superfusion solution altered the NMDA receptor
      mediated component of the synaptic current at the rat cerebellar mossy fibre to
      granule cell synapse. Adding up to 100 microM glycine or d-serine had no effect,
      implying that the glycine site is saturated. Using the competitive glycine site
      antagonist 7-chlorokynurenate, and plausible values for the kinetic parameters of
      NMDA receptors, we estimate that during activation of the mossy fibres the
      concentration of glycine or d-serine in the synaptic cleft is at least 4.6 microM
      or 1.5 microM, respectively, requiring active release of glycine or d-serine.

PMID- 14656294
TI  - The physiological and morphological characteristics of interneurons caudal to the
      trigeminal motor nucleus in rats.
AB  - In this study we have characterized the membrane properties and morphology of
      interneurons which lie between the caudal pole of the trigeminal motor nucleus
      and the rostral border of the facial motor nucleus. Previous studies suggest that
      many of these interneurons may participate in the genesis of rhythmical jaw
      movements. Saggital brainstem slices were taken from rats aged 5-8 days.
      Interneurons lying caudal to the trigeminal motor nucleus were visualized using
      near-infrared differential interference contrast (DIC) microscopy, and were
      recorded from using patch pipettes filled with a K-gluconate- and biocytin-based
      solution. The 127 neurons recorded could be categorized into three subtypes on
      the basis of their responses to injection of depolarizing current pulses, namely
      tonic firing (type I), burst firing (type II) and spike-adaptive (type III)
      neurons. Type I interneurons had a higher input resistance and a lower rheobase
      than type II neurons. All three neuron subtypes showed 'sag' of the voltage
      response to injection of large-amplitude hyperpolarizing current pulses, and, in
      addition, also showed rectification of the voltage response to injection of
      depolarizing current pulses, with type II neurons showing significantly greater
      rectification than type I neurons. The axonal arborizations were reconstructed
      for 44 of 63 neurons labelled with tracer. Neurons of each subtype were found to
      issue axon collaterals terminating in the brainstem nuclei, including the
      parvocellular reticular nucleus (PCRt), the trigeminal motor nucleus (Vmot), the
      supratrigeminal nucleus or the trigeminal mesencephalic nucleus. Twenty-five of
      the 43 neurons issued collaterals which terminated in the Vmot and the other
      brainstem nuclei. When viewed under 100x magnification, the collaterals of some
      interneurons were seen to give off varicosities and end-terminations which passed
      close to the somata of unidentified neurons in the trigeminal motor nucleus and
      in the area close to the interneuron soma itself. This suggests that the
      interneurons may make synaptic contacts both on motoneurons and also on nearby
      interneurons. These results provide data on the membrane properties of trigeminal
      interneurons and evidence for their synaptic connections both with nearby
      interneurons and also with motoneurons. Thus, the interneurons examined could
      play roles in the shaping, and possibly also in the generation, of rhythmical
      signals to trigeminal motoneurons.

PMID- 14656295
TI  - Contribution of spinal inhibitory receptors in heterosegmental antinociception
      induced by noxious stimulation.
AB  - Noxious (i.e. painful) stimulation in the rat induces profound heterosegmental
      antinociception as demonstrated by the ability of either thermal stimulation (50
      degrees C water) or subdermal capsaicin injection in the hindpaw to attenuate the
      nociceptive trigeminal jaw-opening reflex. Importantly, noxious stimulus-induced
      antinociception (NSIA) is mediated by endogenous opioids (as well as other
      neurotransmitters) in nucleus accumbens, as indicated by the ability of intra
      accumbens administration of mu- or delta-opioid receptor antagonists to block
      NSIA. Although noxious peripheral stimulation is known to release excitatory
      neurotransmitters such as glutamate at the level of the spinal cord, the present
      study was designed to test the hypothesis that NSIA depends on further activation
      of spinal inhibitory receptors. This hypothesis was based on findings that
      inhibition of spinal processing (e.g. intrathecal local anaesthetic
      administration) also produces heterosegmental antinociception mediated by
      endogenous opioids in nucleus accumbens. Thus, to reconcile the paradoxical
      findings that both spinal excitation and inhibition appear to activate the same
      nucleus accumbens opioid-mediated antinociceptive mechanism, we investigated
      whether spinal administration of antagonists for inhibitory receptors would block
      the antinociceptive effect of subdermal capsaicin. We report that spinal
      administration of selective antagonists for mu-opioid (Cys2, Tyr3, Orn5,
      Pen7amide), kappa-opioid (nor-binaltorphimine), GABA-A (bicuculline), GABA-B (CGP
      35348) and glycine (strychnine) receptors significantly reduced NSIA. The
      selective delta-opioid receptor antagonist naltrindole had no significant effect.
      These results, together with our previous findings, suggest that peripheral
      noxious stimuli release endogenous opioids, GABA and glycine in the spinal cord
      which, in turn, inhibit tonic pronociceptive spinal activity to produce
      heterosegmental antinociception mediated in nucleus accumbens.

PMID- 14656296
TI  - Light-induced c-fos in melanopsin retinal ganglion cells of young and aged
      rodless/coneless (rd/rd cl) mice.
AB  - Non-rod, non-cone ocular photoreceptors have been shown to mediate a range of
      irradiance detection tasks. The strongest candidates for these receptors are
      melanopsin-positive retinal ganglion cells (RGCs). To provide a more complete
      understanding of these receptors in vivo, we have utilized a mouse that lacks rod
      and cone photoreceptors (rd/rd cl) and compared these animals to congenic wild
      types. Using real-time polymerase chain reaction and immunohistochemistry, we
      address the following. (1) Is Fos expression within these RGCs driven by an input
      from the rods/cones or is it the product of the intrinsic photosensitivity of
      these neurons? We demonstrate that most Fos expression across the entire retina
      is due to the rods/cones, but in the absence of these photoreceptors, light will
      induce Fos within melanopsin RGCs. (2) Could the reported age-related decline in
      circadian photosensitivity of rodents be linked to changes in the population of
      melanopsin RGCs? We show that old mice experience an approximately 40% reduction
      in melanopsin RGCs. (3) Does the loss of inner retinal neurons affect the
      responses of melanopsin RGCs? Aged (approximately 700 days) rd/rd cl mice lose
      most of their inner retina but retain the retinal ganglion cell layer. In these
      mice, the proportion of melanopsin RGCs that express Fos in response to light is
      significantly reduced. Collectively, our data suggest that melanopsin RGCs form a
      heterogeneous population of neurons, and that most of the light-induced c-fos
      expression within these cells is associated with the endogenous photosensitivity
      of these neurons.

PMID- 14656297
TI  - Facilitative role of endogenous oxytocin in noradrenaline release in the rat
      supraoptic nucleus.
AB  - Oxytocin is released not only from the axon terminals in the neurothypophysis but
      also from the dendrites in the hypothalamus. In the present study, we examined
      the role of dendritic oxytocin release in regulating presynaptic noradrenaline
      release within the hypothalamus. In vivo microdialysis experiments showed that
      local application of oxytocin augmented high-K+-induced noradrenaline release in
      the hypothalamic supraoptic nucleus. Oxytocin application to the hypothalamic
      synaptosomal preparation in vitro also potentiated high-K+-induced noradrenaline
      release. The effect of oxytocin was dose-dependent and was blocked by an oxytocin
      receptor antagonist. We then examined roles of oxytocin released from the
      dendrites using in vivo microdialysis. Local application of an oxytocin receptor
      antagonist impaired noradrenaline release in the supraoptic nucleus in response
      to high-K+ solution or noxious stimuli. An i.c.v. injection of an oxytocin
      receptor antagonist also impaired oxytocin release from the pituitary after
      noxious stimuli. These data suggest that dendritic oxytocin facilitates
      activation of oxytocin neurons, at least in part by augmentation of noradrenaline
      release via a presynaptic action.

PMID- 14656298
TI  - Post-lesion transcommissural growth of olivary climbing fibres creates functional
      synaptic microzones.
AB  - In the adult mammalian central nervous system, reinnervation and recovery from
      trauma is limited. During development, however, postlesion plasticity may
      generate alternate paths, providing models to investigate reinnervating axon
      target interactions. After unilateral transection of the neonatal rat
      olivocerebellar path, axons from the ipsilateral inferior olive grow into the
      denervated hemicerebellum and develop climbing fibre (CF)-like arbors on Purkinje
      cells (PCs). However, the synaptic function and extent of PC reinnervation remain
      unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and
      electrophysiological properties of reinnervating olivocerebellar axons were
      studied, using axonal reconstruction and patch-clamp PC recording of CF-induced
      synaptic currents. Reinnervated PCs displayed normal CF currents, and the
      frequency of PC reinnervation decreased with increasing laterality. Reinnervating
      CF arbors were predominantly normal but 6% branched within the molecular layer
      forming smaller secondary arbors. CFs arose from transcommissural olivary axons,
      which branched extensively near their target PCs to produce on average 36 CFs,
      which is six times more than normal. Axons terminating in the hemisphere
      developed more CFs than those terminating in the vermis. However, the precise
      parasagittal microzone organization was preserved. Transcommissural axons also
      branched, although to a lesser extent, to the deep cerebellar nuclei and
      terminated in a distribution indicative of the olivo-cortico-nuclear circuit.
      These results show that reinnervating olivocerebellar axons are highly plastic in
      the cerebellum, compensating anatomically and functionally for early postnatal
      denervation, and that this reparation obeys precise topographic constraints
      although axonal plasticity is modified by target (PC or deep nuclear neurons)
      interactions.

PMID- 14656299
TI  - Electrophysiological characterization of interlaminar entorhinal connections: an
      essential link for re-entrance in the hippocampal-entorhinal system.
AB  - The hippocampal formation communicates with the neocortex mainly through the
      adjacent entorhinal cortex. Neurons projecting to the hippocampal formation are
      found in the superficial layers of the entorhinal cortex and are largely
      segregated from the neurons receiving hippocampal output, which are located in
      deep entorhinal layers. We studied the communication between deep and superficial
      entorhinal layers in the anaesthetized rat using field potential recordings,
      current source density analysis and single unit measurements. We found that
      subiculum stimulation was able to excite entorhinal neurons in deep layers. This
      response was followed by current sinks in superficial layers. Both responses were
      subject to frequency dependent facilitation, but not depression. Selective
      blockade of deep layer responses also abolished subsequent superficial layer
      responses. This clearly demonstrates a functional deep-to-superficial layer
      communication in the entorhinal cortex, which can be triggered by hippocampal
      output. This pathway may provide a means by which processed hippocampal output is
      integrated or compared with new incoming information in superficial entorhinal
      layers, and it constitutes an important link in the process of re-entrance of
      activity in the hippocampal-entorhinal network, which may be important for
      consolidation of memories or retaining information for short periods.

PMID- 14656300
TI  - Rapid modulation of cortical proprioceptive activity induced by transient
      cutaneous deafferentation: neurophysiological evidence of short-term plasticity
      across different somatosensory modalities in humans.
AB  - Single cell recording in non-human primates shows plastic changes of cortical
      somatic representations across different types of somatic inputs originating from
      the same peripheral territory. In humans, muscle afferents from first dorsal
      interosseus are supplied by the ulnar nerve while the cutaneous territory
      overlying this muscle is supplied by the radial nerve. This peculiar anatomical
      nervous distribution allowed us to devise an experimental model which provided a
      unique opportunity to assess, in humans with a non-invasive technique, the
      functional relationships between cutaneous and muscle afferent inputs originating
      from the same peripheral territory. We recorded spinal, brainstem and cortical
      somatosensory potentials evoked by stimulation of muscle afferents of the right
      first dorsal interosseus before, during and after anaesthetic block of the
      sensitive branch of the ipsilateral radial nerve. Amplitude of parietal N20 and
      P27 and frontal N30 somatosensory evoked potential components showed an increase
      of amplitudes with more profound anaesthesia. Amplitudes returned to pre
      anaesthetic values several minutes after anaesthesia. By contrast, spinal N13 and
      brainstem P14 potentials did not change throughout the experiment. Results show,
      for the first time in humans, that a transient cutaneous deafferentation may
      induce rapid modulation of cortical activity evoked by stimulation of muscle
      afferents originating in the anaesthetic territory.

PMID- 14656301
TI  - Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal
      cord injury.
AB  - Assessment of sensory function serves as a sensitive measure for predicting the
      functional outcome following spinal cord injury in patients. However, little is
      known about loss and recovery of sensory function in rodent spinal cord injury
      models as most tests of sensory functions rely on behaviour and thus motor
      function. We used functional magnetic resonance imaging (fMRI) to investigate
      cortical and thalamic BOLD-signal changes in response to limb stimulation
      following mild or moderate thoracic spinal cord weight drop injury in Sprague
      Dawley rats. While there was recovery of close to normal hindlimb motor function
      as determined by open field locomotor testing following both degrees of injury,
      recovery of hindlimb sensory function as determined by fMRI and hot plate testing
      was only seen following mild injury and not following moderate injury. Thus,
      moderate injury can lead to near normal hindlimb motor function in animals with
      major sensory deficits. Recovered fMRI signals following mild injury had a partly
      altered cortical distribution engaging also ipsilateral somatosensory cortex and
      the cingulate gyrus. Importantly, thoracic spinal cord injury also affected
      sensory representation of the upper nonaffected limbs. Thus, cortical and
      thalamic activation in response to forelimb stimulation was significantly
      increased 16 weeks after spinal cord injury compared to control animals. We
      conclude that both forelimb and hindlimb cortical sensory representation is
      altered following thoracic spinal cord injury. Furthermore tests of sensory
      function that are independent of motor behaviour are needed in rodent spinal cord
      injury research.

PMID- 14656302
TI  - Functional heterogeneity of the responses of histaminergic neuron subpopulations
      to various stress challenges.
AB  - In rats, the cell bodies of the histaminergic neuronal system are clustered in
      five distinct cell groups (E1-E5) within the posterior hypothalamus. On the basis
      of tract tracing studies, these histaminergic subgroups have been regarded as one
      functional unit. In addition to its well-characterized role in arousal, locomotor
      activity, metabolism, feeding, drinking and behaviour, as well as in coordination
      of autonomic functions, histamine has been implicated in regulation of the
      hypothalamo-pituitary-adrenocortical axis during stress. To address the capacity
      of different histaminergic subgroups to respond to various challenges, we
      revealed c-Fos, the immediate early gene marker of activated neurons, in
      histamine synthesizing neurons by combining c-Fos immunocytochemistry with in
      situ hybridization of histidine decarboxylase (HDC) mRNA. Compared to the
      negligible colocalization of these markers in control rats, restraint, insulin
      induced hypoglycaemia and foot shock resulted in specific activation of histamine
      synthesizing neurons of the E4 and E5 subgroup in the tuberomammillary region. Up
      to 36% of HDC mRNA-expressing cells show c-Fos immunoreactivity in the E5 region.
      In addition, some neurons of the E1, E2 and E3 histaminergic groups were
      activated after restraint stress. Many less c-Fos-positive histaminergic neurons
      were detected after immobilization and dehydration. Ether stress, acute
      hyperosmotic stimulus or injection of bacterial lipopolysaccharide did not
      activate hypothalamic HDC-positive neurons. These results suggest, for the first
      time, the functional heterogeneity of histaminergic neuron population, the
      components of which are recruited in a stressor- and subgroup-specific manner.

PMID- 14656303
TI  - Protein synthesis in the amygdala, but not the auditory thalamus, is required for
      consolidation of Pavlovian fear conditioning in rats.
AB  - The amygdala is an essential neural substrate for Pavlovian fear conditioning.
      Nevertheless, long-term synaptic plasticity in amygdaloid afferents, such as the
      auditory thalamus, may contribute to the formation of fear memories. We therefore
      compared the influence of protein synthesis inhibition in the amygdala and the
      auditory thalamus on the consolidation of Pavlovian fear conditioning in Long
      Evans rats. Rats received three tone-footshock trials in a novel conditioning
      chamber. Immediately after fear conditioning, rats were infused intra-cranially
      with the protein synthesis inhibitor, anisomycin. Conditional fear to the tone
      and conditioning context was assessed by measuring freezing behaviour in separate
      retention tests conducted at least 24 h following conditioning. Post-training
      infusion of anisomycin into the amygdala impaired conditional freezing to both
      the auditory and contextual stimuli associated with footshock. In contrast, intra
      thalamic infusions of anisomycin or a broad-spectrum protein kinase inhibitor [1
      (5'-isoquinolinesulphonyl)-2-methylpiperazine, H7] did not affect conditional
      freezing during the retention tests. Pre-training intra-thalamic infusion of the
      NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (APV), which blocks
      synaptic transmission in the auditory thalamus, produced a selective deficit in
      the acquisition of auditory fear conditioning. Autoradiographic assays of
      cerebral [14C]-leucine incorporation revealed similar levels of protein synthesis
      inhibition in the amygdala and thalamus following intra-cranial anisomycin
      infusions. These results reveal that the establishment of long-term fear memories
      requires protein synthesis in the amygdala, but not the thalamus, after auditory
      fear conditioning. Forms of synaptic plasticity that depend on protein synthesis,
      such as long-term potentiation, are likely candidates for the encoding and long
      term storage of fear memories in the amygdala.

PMID- 14656304
TI  - Contextual fear conditioning regulates the expression of brain-specific small
      nucleolar RNAs in hippocampus.
AB  - Some small nucleolar RNAs (snoRNAs) are exclusively expressed in the brain but
      they have no known role in higher brain function. We analysed the expression
      pattern of four brain-specific snoRNAs: MBI-36, MBII-48, MBII-52 and MBII-85, in
      mouse brain using in situ hybridization. All of these genes were expressed in the
      hippocampus and, except for MBII-85, their levels in ventral parts were higher
      than those in dorsal parts. Using quantitative real-time polymer chain reaction
      we determined hippocampal expression changes after contextual fear conditioning
      in mice. Ninety minutes, but not 25 h, after conditioning, we observed
      significant downregulation of MBII-48 and upregulation of MBII-52. Our finding
      that the expression of MBII-48 and MBII-52 is regulated during learning suggests
      that these snoRNAs have an important role in higher brain function.

PMID- 14656305
TI  - The neonatal ventral hippocampal lesion model of schizophrenia: effects on
      dopamine and GABA mRNA markers in the rat midbrain.
AB  - The neonatal ventral hippocampal lesion in the rat has been used as a model of
      schizophrenia, a human disorder associated with changes in markers of dopamine
      and gamma-aminobutyric acid (GABA) circuits in various regions of the brain. We
      investigated whether alterations in mRNA markers related to the activity of
      midbrain dopaminergic and GABAergic neurons are associated with this model. We
      used in situ hybridization histochemistry to assess expression of mRNAs for
      dopamine transporter (DAT), tyrosine hydroxylase (TH) and glutamate decarboxylase
      67 (GAD67) in the midbrain of adult rats with neonatal and adult ibotenic acid
      lesions of the ventral hippocampus. Neonatally lesioned rats showed in adulthood
      significantly reduced expression of DAT mRNA in the substantia nigra and the
      ventral tegmental area but no changes in the expression of TH and GAD67 mRNAs in
      these midbrain regions. Adult lesioned rats showed no changes in the expression
      of any of these genes. As the neonatal ventral hippocampal lesion reproduces many
      aspects of schizophrenia and is used as an animal model of this disorder, these
      results suggest that the reduction in DAT mRNA could result from developmental
      neuropathology in the ventral hippocampus and may thus represent a molecular
      substrate of the disease process.

PMID- 14656307
TI  - Alike performance during nonverbal episodic learning from diversely imprinted
      neural networks.
AB  - Performance on neuropsychological testing permits inferences to be made regarding
      neural networks required to solve the task. In healthy young human subjects it is
      common sense that differential performance in cognitive tasks results from
      recruitment of different neural networks and that alike performance results from
      recruitment of alike neural networks. It was the goal of the present study to
      investigate whether these assumptions are also valid in cross-cultural studies.
      To address this, we used functional MRI during a nonverbal episodic memory task
      with repeated learning of abstract geometric patterns. Behavioural performance in
      this task was alike over repeated trials in native Chinese and Caucasian
      subjects. Given this equivalent performance, the distinct pattern of neuronal
      activation observed is interpreted as the outcome of different culturally
      imprinted processing routines. In the 'what' and 'where' framework of visuo
      spatial processing initial learning in Chinese subjects activated the dorsal
      stream for analysis of spatial features whereas Caucasians recruited the ventral
      stream for object identification. With repeated learning Chinese subjects
      integrated visuo-spatial processing to object coding and vice versa. Thus,
      imprints of culture result in activation of distinct neural networks and mandate
      monitoring of both behavioural performance and neural recruitment in cross
      cultural studies of cognition.

PMID- 14656306
TI  - Implication of corticosteroid receptors in the regulation of hippocampal
      structural plasticity.
AB  - The dentate gyrus is one of the few areas of the adult brain that continues to
      produce neurons and to express the embryonic polysialylated isoforms of neuronal
      cell adhesion molecules (PSA-NCAM). The stress hormone corticosterone exerts a
      complex modulation on neurogenesis and PSA-NCAM, and previous studies have shown
      that mature granule cells require corticosterone for their survival. Thus, the
      aim of our work was to investigate the respective role of the different
      corticosteroid receptors on these three parameters in adrenalectomized rats. It
      was found that treatment with a low dose of the mineralocorticoid receptor
      agonist, aldosterone, prevents only the adrenalectomy-induced increase in cell
      death. Treatment with a higher dose of aldosterone normalized cell proliferation
      whereas PSA-NCAM expression was normalized only by treatment with the
      glucocorticoid receptor agonist, RU 28362. It is concluded that stimulation of
      the mineralocorticoid receptor is sufficient to mediate the effects of
      corticosterone on neurogenesis and to protect mature cells from cell death
      whereas stimulation of the glucocorticoid receptor is necessary to modulate PSA
      NCAM expression.

PMID- 14656308
TI  - Transcranial magnetic stimulation of the human frontal eye field facilitates
      visual awareness.
AB  - What are the brain mechanisms allowing a stimulus to enter our awareness? Some
      theories suggest that this process engages resources overlapping with those
      required for action control, but experimental support for these ideas is still
      required. Here, we investigated whether the human frontal eye field (FEF), an
      area known to control eye movements, is involved in visual awareness. Volunteers
      participated in a backward masking task in which they were able to detect a
      target in a small proportion of trials. We observed that a single pulse of
      transcranial magnetic stimulation applied over the FEF shortly before the
      target's onset facilitated visual sensitivity; subjects were able to detect an
      otherwise subliminal object. These results show that modulating the neuronal
      activity of the FEF can enhance visual detection, thereby yielding new insights
      into the neural basis of visual awareness.

PMID- 14656309
TI  - Cortical inhibitory circuits in eye-movement generation.
AB  - The role inhibitory circuits play in target selection with saccadic eye movements
      was examined in area V1, the frontal eye fields (FEF) and the lateral
      intraparietal sulcus (LIP) of the Rhesus Macaque monkey by making local infusions
      of the GABA agonist muscimol and antagonist bicuculline. In V1, both agents
      greatly interfered with target selection and visual discrimination of stimuli
      placed into the receptive field of the affected neurons. In the FEF, bicuculline
      facilitated target selection without affecting visual discrimination and
      generated many spontaneous saccades. Muscimol in the FEF interfered with saccadic
      eye-movement generation. In the LIP, bicuculline was ineffective and muscimol had
      only a small effect. These findings suggest that in the FEF GABAergic inhibitory
      circuits play a central role in eye-movement generation whereas in V1 these
      circuits are essential for visual analysis. Inhibitory circuits in the LIP do not
      appear to play a central role in target selection and in visual discrimination.

PMID- 14656310
TI  - Structural and functional dichotomy of human midcingulate cortex.
AB  - Anterior cingulate cortex is comprised of perigenual and midcingulate regions
      based on cytology, imaging and connections. Its anterior (aMCC) and posterior
      (pMCC) parts and transition to posterior area 23 were evaluated in six human
      cingulate gyri with Nissl staining and immunoreactions for neuron-specific
      nuclear binding protein and intermediate neurofilament proteins (NFP), and their
      pain and emotion functions evaluated in standard coordinates. Morphological
      differences included a poorly differentiated layer III with few NFP-expressing
      neurons in aMCC and a very dense layer Va with small and large pyramids
      intermingled in pMCC. The density of NFP-positive, layer Vb neurons was higher in
      pMCC than in aMCC. The junction of pMCC with area 23 had a dysgranular area 23d
      with clumps of layer IV neurons and a very dense layer Va. Each case was co
      registered to standard coordinates and the regional borders identified and
      measured. Although both regions had overall equivalent activations during noxious
      cutaneous thermal stimulation, the posterior two-thirds of pMCC was relatively
      inactive. About 60% of fear-induced activity was in aMCC, sadness and happiness
      activated perigenual cortex, and neither were activated with non-emotion tasks.
      Thus, pain activity is coupled to fear in aMCC, while other MCC processing is not
      related to affect. Beyond midcingulate duality, this is the first report of a
      very dense layer Va for areas p24' and 23 and the features of transitional area
      23d. The MCC dichotomy suggests that two circuits differentially regulate the two
      cingulate motor areas, and involvement of aMCC in pain and fear make it
      selectively vulnerable to chronic pain and stress syndromes.

PMID- 14656311
TI  - SR141716A reduces the reinforcing properties of heroin but not heroin-induced
      increases in nucleus accumbens dopamine in rats.
AB  - The present experiments tested the hypothesis that the selective CB1 receptor
      antagonist SR141716A alters heroin self-administration by attenuating heroin
      induced increases in nucleus accumbens dopamine levels. SR141716A pretreatment
      dose-dependently (0.3-3 mg/kg, i.p.) reduced operant heroin self-administration
      by male Wistar rats under a fixed ratio schedule of reinforcement, and
      significantly lowered the breaking point of responding for heroin under a
      progressive ratio schedule of reinforcement. These observations are consistent
      with recent reports that CB1 receptor inactivation reduces the rewarding
      properties of opiates. Operant responding for water reinforcement by water
      restricted rats was unaltered by these SR141716A doses. Microdialysis tests
      revealed that heroin self-administration significantly increases interstitial
      dopamine levels in the nucleus accumbens shell of vehicle-pretreated control
      rats. However, whereas SR141716A pretreatment dose-dependently reduced heroin
      self-administration, it did not alter the heroin-associated increase in nucleus
      accumbens dopamine. These findings suggest that the CB1 antagonist-induced
      attenuation of heroin reward does not involve dopaminergic mechanisms in the
      nucleus accumbens shell.

PMID- 14656312
TI  - A role for dendritic protein synthesis in hippocampal late LTP.
AB  - The late temporal component of long-term potentiation (LTP), a putative neural
      mechanism for information storage in the brain, is protein synthesis-dependent,
      but the site of obligatory protein synthesis is not known. Here we show that when
      the protein synthesis inhibitor emetine is applied locally to the apical
      dendritic field of CA1 pyramidal cells in the murine hippocampus, late LTP is
      impaired at apical but not at basal dendrites, and conversely when emetine is
      applied locally to basal dendrites, late LTP is impaired only at basal dendrites.
      Thus, local protein synthesis modulates the expression of tetanically induced
      late LTP at Schaffer-commissural synapses on CA1 pyramidal cells.

PMID- 14656316
TI  - Dynamics of Ca(2+) and Na(+) in the dendrites of mouse cerebellar Purkinje cells
      evoked by parallel fibre stimulation.
AB  - Ca2+ and Na+ play important roles in neurons, such as in synaptic plasticity.
      Their concentrations in neurons change dynamically in response to synaptic
      inputs, but their kinetics have not been compared directly. Here, we show the
      mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in
      Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre
      stimulation (50 Hz, 3-50-times) depolarized Purkinje cells, and Ca2+ transients
      were observed at the anatomically expected sites. The magnitude of the Ca2+
      transients increased linearly with increasing numbers of parallel fibre inputs.
      With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached
      approximately 100 microm, which was much higher than that reported previously,
      although it was still confined to a part of the dendrite. In contrast, Na+
      transients were sustained for tens of seconds and diffused away from the
      stimulated site. Pharmacological interventions revealed that Na+ influx through
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and
      Ca2+ influx through P-type Ca channels were essential players, that AMPA
      receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from
      intracellular stores through inositol trisphosphate receptors or ryanodine
      receptors did not contribute greatly to the large Ca2+ transients.

PMID- 14656317
TI  - Single olfactory sensory neurons simultaneously integrate the components of an
      odour mixture.
AB  - Most odours are complex mixtures. However, the capacities of olfactory sensory
      neurons (OSNs) to process complex odour stimuli have never been explored in air
      breathing vertebrates. To face this issue, the present study compares the
      electrical responses of single OSNs to two odour molecules, delivered singly and
      mixed together, in rats in vivo. This work is the first aimed at demonstrating
      that single OSNs simultaneously integrate several chemical signals and which,
      furthermore, attempts to describe such processes for the whole concentration
      range over which single OSNs can work. The results stress that complex
      interactions occur between components in odour mixtures and that OSN responses to
      such mixtures are not simply predictable from the responses to their components.
      Three types of interactions are described. They are termed suppression,
      hypoadditivity and synergy, in accord with psychophysical terminology. This
      allows us to draw links between peripheral odour reception and central odour
      coding. Indeed, events occurring in single OSNs may account for the dominating or
      even the masking effects of odour molecules in complex mixtures, i.e. for the
      prevailing action of a minor component in the final qualitative perception of a
      mixture. We conclude that our observations with binary mixtures anticipate the
      complexity of processes which may rise at the level of a single OSN in
      physiological conditions. Following this hypothesis, a natural odour would induce
      a multi-chemical integration at the level of single OSNs which may result in
      refining their individual odour-coding properties, leading them to play a crucial
      role in the final performance of the olfactory system.

PMID- 14656318
TI  - Modulation of neuronal activity by the endogenous pentapeptide QYNAD.
AB  - Inflammation and demyelination both contribute to the neurological deficits
      characteristic of multiple sclerosis. Neurological dysfunctions are attributable
      to inflammatory demyelination and, in addition, to soluble factors such as nitric
      oxide, cytokines and antibodies. QYNAD, an endogenous pentapeptide identified in
      the cerebrospinal fluid of patients with demyelinating disorders, has been
      proposed to promote axonal dysfunction by blocking sodium channels. The present
      study aimed at characterizing the properties of QYNAD in acutely isolated
      thalamic neurons in vitro. QYNAD, but not a scrambled peptide (NYDQA), blocked
      sodium channels in neurons by shifting the steady-state inactivation to more
      negative potentials. Blocking properties followed a dose-response curve with a
      maximum effect at 10 microm. A fluorescently labelled QYNAD analogue with
      retained biological activity specifically stained thalamic neurons, positive for
      type II sodium channels, thus demonstrating the specificity of QYNAD binding. Our
      study confirms and extends previous observations describing QYNAD as a potent
      sodium channel-blocking agent. These data as well as our preliminary observations
      in in vivo experiments in an animal model of inflammatory CNS demyelination
      warrant further in vivo studies in order to clarify the exact pathogenetic role
      of QYNAD in inflammatory neurological diseases.

PMID- 14656319
TI  - Adult-born hippocampal neurons mature into activity-dependent responsiveness.
AB  - The mammalian hippocampus is a highly plastic brain structure in which new
      neurons are generated throughout adulthood. Do these new neurons qualitatively
      and quantitatively participate in the activity-dependent gene expression after
      challenging the hippocampus in a learning task? Adult mice were injected with
      bromodeoxyuridine (BrdU) to label dividing cells and indeed, individual BrdU
      labelled new neurons expressed the immediate early gene protein (IEGp) c-fos
      during the acquisition phase of the Morris water maze task to the same extend as
      older granule cells. To assess the responsiveness of all new neurons we also
      analysed the expression patterns of three IEGps (c-fos, zif268 and Homer1A) after
      kainic acid (KA)- or pentylenetetrazol (PTZ)-induced seizures. We found that
      after a maturation period of between 2 and 5 weeks a comparable ratio of adult
      generated granule cells participated in IEGp-expression as in the population of
      older granule cells. Thus, new neurons appear quantitatively integrated into
      hippocampal circuits, suggestive of a relevant contribution to hippocampal
      function.

PMID- 14656320
TI  - Glial cell line-derived neurotrophic factor increases calcitonin gene-related
      peptide immunoreactivity in sensory and motoneurons in vivo.
AB  - Calcitonin gene-related peptide (CGRP) is expressed at high levels in roughly 50%
      of spinal sensory neurons and plays a role in peripheral vasodilation as well as
      nociceptive signalling in the spinal cord. Spinal motoneurons express low levels
      of CGRP; motoneuronal CGRP is thought to be involved in end-plate plasticity and
      to have trophic effects on target muscle cells. As both sensory and motoneurons
      express receptors for glial cell line-derived neurotrophic factor (GDNF) we
      sought to determine whether CGRP was regulated by GDNF. Rats were treated
      intrathecally for 1-3 weeks with recombinant human GDNF or nerve growth factor
      (NGF) (12 microg/day) and dorsal root ganglia and spinal cords were stained for
      CGRP. The GDNF treatment not only increased CGRP immunoreactivity in both sensory
      and motoneurons but also resulted in hypertrophy of both populations. By combined
      in situ hybridization and immunohistochemistry we found that, in the dorsal root
      ganglia, CGRP was up-regulated specifically in neurons expressing GDNF but not
      NGF receptors following GDNF treatment. Despite the increase in CGRP in GDNF
      treated rats, there was no increase in thermal or mechanical pain sensitivity,
      while NGF-treated animals showed significant decreases in pain thresholds. In
      motoneurons, GDNF increased the overall intensity of CGRP immunoreactivity but
      did not increase the number of immunopositive cells. As GDNF has been shown to
      promote the regeneration of both sensory and motor axons, and as CGRP appears to
      be involved in motoneuronal plasticity, we reason that at least some of the
      regenerative effects of GDNF are mediated through CGRP up-regulation.

PMID- 14656321
TI  - Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects
      of gamma-hydroxybutyrate in GABA(B)(1)-deficient mice.
AB  - gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is
      proposed to function as a neurotransmitter or neuromodulator. gamma
      Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received
      increased public attention as they emerged as popular drugs of abuse. The actions
      of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors,
      the latter corresponding to high-affinity [3H]GHB-binding sites coupled to G
      proteins. To investigate the contribution of GABAB receptors to GHB actions we
      studied the effects of GHB in GABAB(1)-/- mice, which lack functional GABAB
      receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB
      binding sites in brains of GABAB(1)-/- and wild-type mice. The maximal number of
      binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9
      tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene acetic acid (NCS-382) appear
      unchanged in GABAB(1)-/- compared with wild-type mice, demonstrating that GHB-
      are distinct from GABAB-binding sites. In the presence of the GABAB receptor
      positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol GHB
      induced functional GTPgamma[35S] responses in brain membrane preparations from
      wild-type but not GABAB(1)-/- mice. The GTPgamma[35S] responses in wild-type mice
      were blocked by the GABAB antagonist [3-[[1-(S)-(3,4dichlorophenyl)ethyl]amino]-2
      (S)-hydroxy-propyl]-cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but
      not by NCS-382. Altogether, these findings suggest that the GHB-induced
      GTPgamma[35S] responses are mediated by GABAB receptors. Following GHB or GBL
      application, GABAB(1)-/- mice showed neither the hypolocomotion, hypothermia,
      increase in striatal dopamine synthesis nor electroencephalogram delta-wave
      induction seen in wild-type mice. It, therefore, appears that all studied GHB
      effects are GABAB receptor dependent. The molecular nature and the signalling
      properties of the specific [3H]GHB-binding sites remain elusive.

PMID- 14656322
TI  - Microglial activation with atypical proinflammatory cytokine expression in a rat
      model of Parkinson's disease.
AB  - Microglial activation has been associated with the pathogenesis of Parkinson's
      disease (PD). Among the many components of this reaction, cytokines have been
      proposed as candidates to mediate neurodegenerative or neuroprotective effects.
      We investigated the interleukin-1 system and tumour necrosis factor-alpha mRNA
      and protein levels at different time intervals in the subacute intrastriatal 6
      hydroxydopamine rat model of PD, in parallel with the inflammatory response.
      Immunohistochemistry showed that microglial cells were activated from days 6-30
      postlesion in the substantia nigra pars compacta. This microglial activation was
      accompanied by an atypical proinflammatory cytokine production: Interleukin
      1alpha and beta mRNAs were found to be elevated 30 days post-6-hydroxydopamine
      injection (2- and 16-fold, respectively), but no induction for interleukin-1alpha
      or beta at the protein level was detected by ELISA. As a control, a classical
      proinflammatory stimulus, namely endotoxin, was capable of inducing these
      cytokines at similar mRNA levels but also at the protein level. In addition,
      tumour necrosis factor-alpha mRNA was hardly or not detected in the substantia
      nigra at any time point studied. Our data point out a tight control of key
      proinflammatory cytokine production in our model of PD. This work supports the
      notion that chronic neuronal death per se does not induce secretion of these
      proinflammatory cytokines but that an additional stimulus is necessary to
      stimulate proinflammatory cytokine production. The production of proinflammatory
      cytokines from "primed" microglia may in turn modulate disease progression as has
      been recently proposed in a model of prion disease.

PMID- 14656323
TI  - Depression of mGluR-mediated IPSCs by 5-HT in dopamine neurons of the rat
      substantia nigra pars compacta.
AB  - Dopamine neurons of the substantia nigra pars compacta receive a prominent
      serotonin (5-HT) projection from the dorsal raphe nucleus and important
      functional interactions between the serotonergic and the dopaminergic system have
      been postulated. In the present report we examined the role of 5-HT in the
      modulation of the metabotropic glutamate receptor-mediated inhibitory
      postsynaptic current (mGluR-IPSC) in midbrain dopamine neurons, and we found a
      reversible depression of this synaptic response at concentrations of 5-HT ranging
      from 100 nm to 30 microm (EC50 1.06 microm). This resulted in a shift towards
      excitation of the overall dopamine neuron response to glutamatergic synaptic
      input. This effect was not because of a direct modulation of the Ca2+-sensitive
      K+ conductances underlying the mGluR-IPSC, but was associated with a decrease in
      the intracellular calcium signal triggered by mGluR stimulation. Similar results
      were obtained with alpha-methyl-5-hydroxytryptamine and 5-methoxytryptamine, but
      not with 5-carboxamidotryptamine or 1-(3-chlorophenyl) piperazine. No significant
      depression of the mGluR-IPSC by 5-HT was observed in the presence of the 5-HT2
      antagonist cinanserin or the 5-HT4 receptor antagonist RS 23597-190, whereas the
      5-HT2C antagonist RS 102221 was ineffective. Our results demonstrate a powerful
      inhibition of the mGluR-IPSC by 5-HT in midbrain dopamine neurons, most probably
      through stimulation of 5-HT2A and 5-HT4 receptors.

PMID- 14656324
TI  - Inhibitory effect of mouse neocortex layer I on the underlying cellular network.
AB  - The mammalian cortical layer I is a convergence site for axons of sub- and
      intracortical origin, and the apical dendritic tufts of pyramidal neurons. A
      prominent feature of layer I is an extensive plexus of inhibitory axons, which
      originate from stellate cells in all cortical laminae. The role of this
      inhibitory projection in the activity of cortical networks has yet to be
      determined. We investigated the degree to which inhibitory inputs within layer I
      affect the activity of the underlying cellular network. Field potentials (FPs)
      were recorded in layer II/III. Focal application of the GABAA blocker picrotoxin
      in layer I above the recording pipette or the removal of layer I resulted in
      larger FP amplitudes for stimulations at control-equal intensities. When
      inhibition was partially blocked, the removal of layer I caused a significant
      reduction in the threshold stimulus intensity required for generating
      epileptiform events, and a rise in the propagation velocity of these events.
      Immunocytochemistry for chemical markers of interneurons proved that the
      inhibitory input to layer I is predominantly somatostatin immunoreactive (SM-ir),
      such that layer I contains approximately one-third of all SM-ir axons in the
      cortex. Calretinin-immunoreactive axons were also present in layer I at a lower
      density. We conclude that the impact of layer I on the cortical cellular network
      includes a significant inhibitory component. This inhibition confers a moderate
      restraining influence, and its removal increases the excitability of cortical
      circuits, but not sufficiently to induce epileptic phenomena.

PMID- 14656325
TI  - Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived
      neurotrophic factor synthesis and release by the rodent uterus.
AB  - Sympathetic innervation of the adult rodent uterus undergoes cyclic remodelling.
      Terminal sympathetic axons degenerate when oestrogen levels rise and regenerate
      when oestrogen levels decline. This study examined the role of neurotrophins in
      oestrogen-mediated uterine sympathetic nerve remodelling. Oestrogen injection of
      ovariectomized female rats did not affect uterine NT-3 levels 24 h postinjection,
      and increased endometrial NGF protein, indicating that reduced NGF or NT-3 is not
      responsible for the oestrogen-induced denervation. Oestrogen also raised BDNF
      protein and mRNA in myometrium and endometrium. To assess whether increased BDNF
      affects uterine receptivity to sympathetic outgrowth, sympathetic ganglion
      explants were co-cultured with myometrium. Myometrium from ovariectomized rats
      induced neuritogenesis in oestrogen-free conditions, and this was abolished when
      BDNF was added to the medium. Neuritogenesis induced by ovariectomized myometrium
      was suppressed by oestrogen, and restored by a BDNF function-blocking antibody.
      To determine if target BDNF synthesis is required for oestrogen to suppress
      sympathetic neurite outgrowth, uteri from wild-type mice and mice homozygous or
      heterozygous for recombinant mutations of the BDNF gene were cultured with rat
      sympathetic ganglia. Neuritogenesis induced by wild-type uteri was diminished by
      oestrogen. Neurite formation in the presence of homozygous BDNF mutant uteri was
      not affected by oestrogen, but was lower than that of wild-type mice. Uteri from
      mice heterozygous for the BDNF mutation, who have reduced BDNF synthesis, showed
      normal neuritogenic properties, but were not affected by oestrogen. These
      findings suggest that oestrogen alters neuritogenic properties of the rodent
      uterus by regulating BDNF synthesis, which inhibits sympathetic neurite
      outgrowth.

PMID- 14656326
TI  - Seizures preferentially stimulate proliferation of radial glia-like astrocytes in
      the adult dentate gyrus: functional and immunocytochemical analysis.
AB  - Kainate-induced seizures increase hippocampal neurogenesis. Glial fibrillary
      acidic protein-positive astrocytes with radial processes in the dentate gyrus
      share many of the characteristics of radial glia and appear to act as precursor
      cells for adult dentate neurogenesis. Using the chemoconvulsant kainate and
      transgenic mice with human glial-fibrillary acidic protein (hGFAP) promoter
      controlled enhanced green fluorescent protein (EGFP) expression, we examined the
      proliferation, morphology and electrophysiological properties of astrocytes in
      the neurogenic subgranular zone of the dentate gyrus in control animals and upon
      the induction of seizure-induced cell proliferation, three days post-kainate.
      EGFP-positive cells with and without radial processes could easily be
      distinguished. Kainate treatment caused a significant increase in the total
      number of proliferating EGFP-positive cells, particularly a tenfold elevation in
      the number of proliferating radial glia-like astrocytes, and also caused a
      preferential shift in the dividing cell population towards cells expressing EGFP.
      Immunohistochemical analysis revealed a surprisingly low proportion of cells
      coexpressing the astroglial marker S100beta and EGFP. Kainate increased the
      number of EGFP-positive, S100beta-positive and S100beta-positive-EGFP-positive
      astrocytes in the subgranular zone. We also report a subset of faintly EGFP
      positive cells expressing markers of early neuronal differentiation. Patch-clamp
      analysis revealed the presence of three functionally different populations of
      EGFP-positive cells in both kainate and control tissue. We conclude that there is
      an early increase in proliferating radial glia-like astrocytes in the dentate
      after kainate-induced seizures, consistent with a recruitment of precursors for
      seizure-induced neurogenesis.

PMID- 14656327
TI  - Synaptic and non-synaptic mechanisms of amygdala recruitment into temporolimbic
      epileptiform activities.
AB  - Lateral amygdala (LA) activity during synchronized-epileptiform discharges in
      temporolimbic circuits was investigated in rat horizontal slices containing the
      amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt)
      cortex, through multiple-site extra- and intracellular recording techniques and
      measurement of the extracellular K+ concentration. Application of 4-aminopyridine
      (50 microm) induced epileptiform discharges in all regions under study. Slow
      interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection
      of the Hip, seemed to originate in the Prh as shown from time delay analyses, and
      often preceded the onset of ictal-like activity. Disconnection of the amygdala
      resulted in de-synchronization of epileptiform discharges in the LA from those in
      the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA
      projection neurons as gamma-aminobutyric acid (GABA)A/B receptor-mediated
      synaptic responses, and depolarizing electrogenic events (spikelets) residing on
      the initial phase of the GABA response. Spikelets were considered antidromically
      conducted ectopic action potentials generated at axon terminals, as they were
      graded in amplitude, were not abolished through hyperpolarizing membrane
      responses (which effectively blocked evoked orthodromic action potentials),
      lacked a clear prepotential or synaptic potential, were not affected through
      blockers of gap junctions, and were blocked through remote application of
      tetrodotoxin at putative target areas of LA projection neurons. Remote
      application of a GABAB receptor antagonist facilitated spikelet generation. A
      transient elevation in the extracellular K+ level averaging 3 mm above baseline
      occurred in conjunction with interictal-like activity in all areas under study.
      We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a
      predictable manner through the synaptic network with the Prh playing a leading
      role. The rise in extracellular K+ may provide a depolarizing mechanism for
      recruitment of interneurons and generation of ectopic action potentials at axon
      terminals of LA projection neurons. Antidromically conducted ectopic action
      potentials may provide a spreading mechanism of seizure activity mediated by
      diffuse axonal projections of LA neurons.

PMID- 14656328
TI  - Correlated stage- and subfield-associated hippocampal gene expression patterns in
      experimental and human temporal lobe epilepsy.
AB  - Epileptic activity evokes profound alterations of hippocampal organization and
      function. Genomic responses may reflect immediate consequences of excitatory
      stimulation as well as sustained molecular processes related to neuronal
      plasticity and structural remodeling. Using oligonucleotide microarrays with 8799
      sequences, we determined subregional gene expression profiles in rats subjected
      to pilocarpine-induced epilepsy (U34A arrays, Affymetrix, Santa Clara, CA, USA; P
      < 0.05, twofold change, n = 3 per stage). Patterns of gene expression
      corresponded to distinct stages of epilepsy development. The highest number of
      differentially expressed genes (dentate gyrus, approx. 400 genes and CA1, approx.
      700 genes) was observed 3 days after status epilepticus. The majority of up
      regulated genes was associated with mechanisms of cellular stress and injury - 14
      days after status epilepticus, numerous transcription factors and genes linked to
      cytoskeletal and synaptic reorganization were differentially expressed and, in
      the stage of chronic spontaneous seizures, distinct changes were observed in the
      transcription of genes involved in various neurotransmission pathways and between
      animals with low vs. high seizure frequency. A number of genes (n = 18)
      differentially expressed during the chronic epileptic stage showed corresponding
      expression patterns in hippocampal subfields of patients with pharmacoresistant
      temporal lobe epilepsy (n = 5 temporal lobe epilepsy patients; U133A microarrays,
      Affymetrix; covering 22284 human sequences). These data provide novel insights
      into the molecular mechanisms of epileptogenesis and seizure-associated cellular
      and structural remodeling of the hippocampus.

PMID- 14656329
TI  - VEGF is necessary for exercise-induced adult hippocampal neurogenesis.
AB  - Declining learning and memory function is associated with the attenuation of
      adult hippocampal neurogenesis. As in humans, chronic stress or depression in
      animals is accompanied by hippocampal dysfunction, and neurogenesis is
      correspondingly down regulated, in part, by the activity of the hypothalamic
      pituitary-adrenal axis as well as glutamatergic and serotonergic networks.
      Antidepressants can reverse this effect over time but one of the most clinically
      effective moderators of stress or depression and robust stimulators of
      neurogenesis is simple voluntary physical exercise such as running. Curiously,
      running also elevates circulating stress hormone levels yet neurogenesis is
      doubled in running animals. In evaluating the signalling that running provides to
      the central nervous system in mice, we have found that peripheral vascular
      endothelial growth factor (VEGF) is necessary for the effects of running on adult
      hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced
      neurogenesis but had no detectable effect on baseline neurogenesis in non-running
      animals. These data suggest that VEGF is an important element of a 'somatic
      regulator' of adult neurogenesis and that these somatic signalling networks can
      function independently of the central regulatory networks that are typically
      considered in the context of hippocampal neurogenesis.

PMID- 14656330
TI  - Gradient of adaptability in four different motor systems performing the same
      learned motor task in cats.
AB  - The ability of four different brainstem motoneuron pools to perform a newly
      acquired motor task was studied in alert cats. A classical conditioning of eyelid
      responses was carried out in (i). unoperated animals, and in animals with (ii).
      transection, 180 degrees rotation, and re-suture of the zygomatic facial nerve
      branch, (iii). a crossed anastomosis of the buccal to the zygomatic facial nerve
      branch and (iv). a hypoglossal-facial nerve anastomosis. Animals were conditioned
      with a delay paradigm using a tone (350 ms, 600 Hz, 90 dB) as conditioned
      stimulus, followed 250 ms later by an air puff (100 ms, 3 kg/cm2) as
      unconditioned stimulus. Animals with zygomatic nerve rotation performed
      conditioned responses (CRs) at control rate, with significantly larger amplitude,
      area and velocity, but a de-synchronized oscillatory pattern. Animals with buccal
      zygomatic anastomosis acquired CRs at control rate, but these CRs had
      significantly smaller amplitude than those of controls and a de-synchronized
      pattern. Animals with a hypoglossal-facial anastomosis were unable to perform
      CRs. The trigeminal hyper-reflexia triggered by the axotomy was probably the
      origin of the large CRs after zygomatic nerve rotation. Trigeminal hyper-reflexia
      could also contribute to generation of the small CRs recorded after buccal
      zygomatic anastomosis. Although trigeminal hyper-reflexia was also present
      following hypoglossal-facial anastomosis, hypoglossal motoneurons did not reach
      their firing threshold to perform CRs. In accordance with the embryonic origin of
      involved motoneurons, animals with buccal-zygomatic and hypoglossal-facial
      anastomoses moved the ipsilateral eyelid synchronously to mouth-related
      activities. It is suggested that there is a gradient of adaptability in
      motoneuron pools forced to perform new motor tasks through foreign muscles, which
      depends on their embryological origins and functional properties.

PMID- 14656331
TI  - Context-specific acquisition of location discrimination by hippocampal place
      cells.
AB  - The spatially localized firing of rodent hippocampal place cells is strongly
      determined by the local geometry of the environment. Over time, however, the
      cells can acquire additional inputs, including inputs from more distal cues. This
      is manifest as a change in firing pattern ('remapping') when the new inputs are
      manipulated. Place cells also reorganize their firing in response to non
      geometric changes in 'context', such as a change in the colour or odour of the
      environment. The present study investigated whether the new inputs acquired by
      place cells in one context were still available to the cells when they expressed
      their altered firing patterns in a new context. We found that the acquired
      information did not transfer to the new context, suggesting that the context
      inputs and the acquired inputs must interact somewhere upstream of the place
      cells themselves. We present a model of one possible such interaction, and of how
      such an interaction could be modified by experience in a Hebbian manner, thus
      explaining the context specificity of the new learning.

PMID- 14656332
TI  - Hippocampal gene expression profiles in passive avoidance conditioning.
AB  - Many experiments in the past have demonstrated the requirement of de novo gene
      expression during the long-term retention of learning and memory. Although
      previous studies implicated individual genes or genetic pathways in learning and
      memory, the collective behaviours of the genes is mostly unknown. We have used
      genome-scale screening by microarray analysis to examine the hippocampal
      expression of more than 1200 genes relevant to neurobiology during instrumental
      conditioning. Training rats on a step-through passive avoidance task led to
      unique patterns of gene expression when compared to naive animals or those
      exposed to the conditioned or the unconditioned stimulus alone. The newly
      identified genes afford a quantitative view of the changes which accompany
      conditioning at the genomic level and enable deeper insights into the molecular
      basis underlying learning and memory.

PMID- 14656333
TI  - Enrichment enhances the expression of sgk, a glucocorticoid-induced gene, and
      facilitates spatial learning through glutamate AMPA receptor mediation.
AB  - We have previously demonstrated that the serum and glucocorticoid-inducible
      kinase (sgk) gene plays a causal role in facilitating memory performance in rats.
      Environment enrichment is known to facilitate spatial learning. We therefore
      examined the effect of enrichment on sgk expression. We also examined the role of
      sgk in spatial and nonspatial learning and the regulation of sgk expression by
      activation of different glutamate receptors. Both real-time polymerase chain
      reaction and Western blot analyses revealed that enrichment training
      preferentially increased sgk mRNA and protein levels in the hippocampus.
      Transfection of sgk mutant DNA to the hippocampal CA1 area markedly impaired
      spatial learning, fear-conditioning learning and novel object-recognition
      learning in rats, but enrichment training effectively reversed these learning
      deficits. Meanwhile, S422A mutant DNA transfection prevented enrichment-induced
      spatial learning facilitation. In studying glutamate receptor regulation of sgk
      expression, we found that blockade of N-methyl-d-aspartate (NMDA) receptors in
      general, and the NR2B subunit in particular both effectively blocked enrichment
      induced spatial learning facilitation, but they did not block enrichment-induced
      sgk expression. Upon various glutamate agonist infusions, only alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) increased sgk mRNA levels
      significantly in the hippocampus. Furthermore, blockade of AMPA receptors
      effectively blocked both enrichment-induced spatial learning facilitation and sgk
      expression. These results indicate that there is a dissociation between NMDA
      receptor activation and sgk expression. Enrichment enhanced spatial learning
      through both NMDA and AMPA receptor activation, whereas enrichment-induced sgk
      expression is specifically mediated through AMPA receptors. These results suggest
      that sgk could serve as a novel molecular mechanism, in addition to the NMDA
      receptor NR2B, underlying enrichment-induced learning facilitation.

PMID- 14656334
TI  - Ear of stimulation determines schizophrenia-normal brain activity differences in
      an auditory paired-stimuli paradigm.
AB  - Schizophrenia patients have abnormalities of auditory information processing,
      theoretically associated with dysfunction of neuronal excitation. Auditory paired
      stimuli (S1-S2) paradigms are used to evaluate the nature of these abnormalities.
      It is unknown whether patients' abnormalities during S1-S2 paradigms are
      attributable to specific hemispheric differences in cortical processing. The
      present studies used whole head magnetoencephalography and monaural or binaural
      versions of the paired-stimuli paradigm to evaluate auditory processing among 38
      schizophrenia and 38 normal subjects. The strengths of auditory-evoked brain
      responses over time were quantified using distributed source reconstructions with
      L2 minimum norm constraint and realistic head models. For left ear stimuli,
      schizophrenia and normal groups did not differ on either left or right hemisphere
      activity over auditory cortex. For right ear and binaural stimuli, schizophrenia
      patients had less activity over left auditory cortex from 80 to 120 ms post
      stimulus but did not differ from normal on activity over right auditory cortex.
      Additionally, in response to monaural stimulation, schizophrenia patients had
      significantly less activity than normal over right temporal parietal junction
      from 60 to 120 ms post-stimulus. These data are consistent with four propositions
      about schizophrenia: (i). right auditory cortex is functioning normally; (ii).
      processing of simple auditory stimuli is abnormal in left auditory cortex,
      probably specifically in supra-granular layers; (iii). auditory localization
      abilities are deficient; and (iv). auditory cortex abnormalities are not a
      function of deficient hemispheric communication because they are evident early in
      processing as long as stimuli are delivered directly to left hemisphere.

PMID- 14656335
TI  - Pain processing within the primary somatosensory cortex in humans.
AB  - To investigate the processing of noxious stimuli within the primary somatosensory
      cortex (SI), we recorded magnetoencephalography following noxious epidermal
      electrical stimulation (ES) and innocuous transcutaneous electrical stimulation
      (TS) applied to the dorsum of the left hand. TS activated two sources
      sequentially within SI: one in the posterior bank of the central sulcus and
      another in the crown of the postcentral gyrus, corresponding to Brodmann's areas
      3b and 1, respectively. Activities from area 3b consisted of 20- and 30-ms
      responses. Activities from area 1 consisted of three components peaking at 26, 36
      and 49 ms. ES activated one source within SI whose location and orientation were
      similar to those of the TS-activated area 1 source. Activities from this source
      consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than
      the corresponding TS responses. ES and TS subsequently activated a similar region
      in the upper bank of the sylvian fissure, corresponding to the secondary
      somatosensory cortex (SII). The onset latency of the SII activity following ES
      (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise,
      the onset latency of SII activity following TS (52 ms) was later by 35 ms than
      that of area 1 of SI (17 ms). Therefore, our results showed that the processing
      of noxious and innocuous stimuli is similar with respect to the source locations
      and activation timings within SI and SII except that there were no detectable
      activations within area 3b following noxious stimulation.

PMID- 14656336
TI  - Engagement of visual fixation suppresses sensory responsiveness and multisensory
      integration in the primate superior colliculus.
AB  - Neurons in the intermediate and deep layers of the superior colliculus (SC) often
      exhibit sensory-related activity in addition to discharging for saccadic eye
      movements. These two patterns of activity can combine so that modifications of
      the sensory response can lead to changes in orienting behaviour. Can behavioural
      factors, however, influence sensory activity? In this study of rhesus monkeys, we
      isolate one behavioural factor, the state of visual fixation, and examine its
      influences on sensory processing and multisensory integration in the primate SC.
      Two interleaved fixation conditions were used: a FIX condition requiring
      exogenous fixation of a visible fixation point; and a FIX-BLINK condition,
      requiring endogenous fixation in the absence of a visible fixation point. Neurons
      of the SC were influenced by fixation state, exhibiting both lower levels of
      sensory activity and reduced multisensory interactions when fixation was
      exogenously engaged on a visible fixation point. These results are consistent
      with active visual fixation suppressing responses to extraneous stimuli, and thus
      demonstrate that sensory processing and multisensory responses in the SC are not
      dependent solely on the physical properties of the sensory environment, but are
      also dynamically influenced by the behavioural state of the animal.

PMID- 14656337
TI  - Mechanisms of time-based figure-ground segregation.
AB  - Figure-ground segregation can rely on purely temporal information, that is, on
      short temporal delays between positional changes of elements in figure and ground
      (Kandil, F.I. & Fahle, M. (2001) Eur. J. Neurosci., 13, 2004-2008). Here, we
      investigate the underlying mechanisms by measuring temporal segregation
      thresholds for various kinds of motion cues. Segregation can rely on monocular
      first-order motion (based on luminance modulation) and second-order motion cues
      (contrast modulation) with a high temporal resolution of approximately 20 ms. The
      mechanism can also use isoluminant motion with a reduced temporal resolution of
      60 ms. Figure-ground segregation can be achieved even at presentation frequencies
      too high for human subjects to inspect successive frames individually. In
      contrast, when stimuli are presented dichoptically, i.e. separately to both eyes,
      subjects are unable to perceive any segregation, irrespective of temporal
      frequency. We propose that segregation in these displays is detected by a
      mechanism consisting of at least two stages. On the first level, standard motion
      or flicker detectors signal local positional changes (flips). On the second
      level, a segregation mechanism combines the local activities of the low-level
      detectors with high temporal precision. Our findings suggest that the segregation
      mechanism can rely on monocular detectors but not on binocular mechanisms.
      Moreover, the results oppose the idea that segregation in these displays is
      achieved by motion detectors of a higher order (motion-from-motion), but favour
      mechanisms sensitive to short temporal delays even without activation of higher
      order motion detectors.

PMID- 14656338
TI  - Sensorimotor memory and grip force control: does grip force anticipate a self
      produced weight change when drinking with a straw from a cup?
AB  - We examined whether self-generated weight changes are anticipated by adequate
      grip force adjustments when repeatedly lifting an instrumented manipulandum.
      Subjects lifted a cup filled with 500 mL of water prior to and following drinking
      two portions of water with a straw without touching it. One half of the subjects
      drank from and lifted an uncovered cup receiving constant visual information
      about its filling level and the other half of the subjects drank from a covered
      cup without such visual feedback. During the lifts immediately following the
      drinking procedures, grip force scaling was erroneously programmed for the
      heavier weight of the preceding lift as was obvious from an inadequately high
      rate of grip force development. Vision had only a minor influence on the rate of
      grip force increase. The influence of vision on the scaling of peak grip force
      was more pronounced. More accurate force scaling was obtained with an increasing
      number of lifts performed under each weight condition, indicating an ongoing
      force adjustment process probably based on sensory feedback. We conclude that
      self-generation of a change in the weight of an object to be lifted is not, in
      itself, sufficient to elicit a predictive grip force output. Rather, accurate
      feedback information associated with the self-generated weight change is
      essential to update internal models related to the mechanical object properties.
      This assumption was confirmed in pilot experiments; when subjects lifted the cup
      after having poured water from it, they accurately scaled their fingertip force
      to the self-produced weight change. Here, direct sensory feedback from the
      grasping fingers could signal the weight change and update internal models while
      pouring water from the cup. Our data support the hypothesis that the sensorimotor
      system planning and processing predictive fingertip force can operate
      independently of higher-level cognitive and perceptual systems.

PMID- 14656339
TI  - Chemokine modulation of high-conductance Ca(2+)-sensitive K(+) currents in
      microglia from human hippocampi.
AB  - During acute pathological processes, microglia transform into an activated state
      characterized by a defined morphology and current profile, and are recruited to
      injury sites by chemokines. No information is available on the ion channels and
      the mode of action of chemokines in microglia in brain slices from humans with a
      chronic pathology. Thus, patch-clamp recordings of microglia were performed in
      hippocampal slices from seven patients who underwent surgery for pharmaco
      resistant epilepsy. Cells were identified as microglia by positive labelling with
      fluorescein-conjugated tomato lectin before recording. All the recorded cells had
      an ameboid morphology characteristic of activated microglia. However, they had a
      high input resistance (3.6 G omega), a zero-current resting potential of -16 mV,
      and lacked Na+ currents, inwardly rectifying and delayed rectifying K+ currents
      such as non-activated microglia. Importantly, recorded cells expressed Ca2+
      sensitive outward currents that activated at 0 mV with non-buffered intracellular
      Ca2+ and were sensitive to 1 mm tetraethylammonium (TEA). The estimated single
      channel conductances were 187 pS in cell-attached and 149 pS in outside-out
      patches, similar to those of high-conductance Ca2+-dependent K+ channels. The
      chemokine MIP1-alpha increased whole-cell outward current amplitudes measured at
      +60 mV by a factor of 3.3. Thus, microglia in hippocampi from epileptic patients
      express high-conductance Ca2+-dependent K+ channels that are modulated by the
      chemokine MIP1-alpha. This modulation may contribute to the migratory effect of
      MIP1-alpha on microglia.

PMID- 14656340
TI  - Non-calyceal excitatory inputs mediate low fidelity synaptic transmission in rat
      auditory brainstem slices.
AB  - Principal neurons of the medial nucleus of the trapezoid body (MNTB) receive a
      synaptic input from a single giant calyx terminal that generates a fast-rising,
      large excitatory postsynaptic current (EPSC), each of which are supra-threshold
      for postsynaptic action potential generation. Here, we present evidence that MNTB
      principal neurons receive multiple excitatory synaptic inputs generating slow
      rising, small EPSCs that are also capable of triggering postsynaptic action
      potentials but are of non-calyceal origin. Both calyceal and non-calyceal EPSCs
      are mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and
      N-methyl-d-aspartate (NMDA) receptor activation; however, the NMDA receptor
      mediated response is proportionally larger at the non-calyceal synapses. Non
      calyceal synapses generate action potentials in MNTB principal neurons with a
      longer latency and a lower reliability than the large calyceal input. They
      constitute an alternative low fidelity synaptic input to the fast and secure
      relay transmission via the calyx of Held synapse.

PMID- 14656341
TI  - Maternal care influences neuronal survival in the hippocampus of the rat.
AB  - Maternal care during the first week of postnatal life influences hippocampal
      development and function (Liu et al., 2000; Nature Neurosci., 3, 799-806).
      Offspring reared by mothers who exhibit increased levels of pup licking/grooming
      (LG) show increased hippocampal synaptic density and enhanced spatial learning
      and memory. Using 5-bromo-2'-deoxyuridine (BrdU), a thymidine analogue
      incorporated into cells during DNA synthesis, we examined the effects of early
      maternal care on hippocampal cell proliferation and neuronal survival in the rat.
      Twenty-four hours following injection on day 7 of life (P7) there were no
      differences in BrdU labelling in the offspring of high- compared with low-LG
      mothers, suggesting no maternal effect on the rate of proliferation at this age.
      However, 14 and 83 days following injection (P21 and P90), the offspring of high
      LG mothers had significantly more surviving BrdU-labelled cells and BrdU-NeuN+
      colabelled neurons in the dentate gyrus subgranular zone and granule cell layer.
      At P21, the offspring of high-LG mothers showed increased protein expression of
      basic fibroblast growth factor and significantly decreased levels of pyknosis.
      These findings suggest an influence of maternal care on neuronal survival in the
      hippocampus. Conversely, at the same time point there was a significantly higher
      level of hippocampal glial fibrillary acidic protein expression in the offspring
      of low-LG mothers. These findings emphasize the importance of early maternal care
      for hippocampal development.

PMID- 14656343
TI  - Delay-period activities in two subdivisions of monkey inferotemporal cortex
      during pair association memory task.
AB  - The macaque inferotemporal cortex, which is involved in encoding and retrieval of
      visual long-term memory, consists of two distinct but mutually interconnected
      areas: area TE (TE) and area 36 (A36). In the present study, we compared delay
      period activities of the two subdivisions in terms of their signal contents. We
      recorded single-unit activities from TE and A36 during a delayed pair association
      task, in which monkeys were required to choose the paired associate of a cue
      stimulus after a delay period. The stimulus-selective delay-period activities of
      single neurons were characterized by using partial correlation coefficients of
      delay-period activities for each cue stimulus with the cue-period responses to
      that stimulus (cue-holding index, CHI) and with the cue-period responses to its
      paired associate (pair-recall index, PRI). The delay-period activities of TE
      neurons preferentially represented the paired associate (PRI, median = 0.54)
      rather than the cue stimulus itself (CHI, 0.23) (P < 0.001, n = 70), while the
      delay-period activities of A36 neurons retained both the cue stimulus and its
      paired associate equivalently (CHI, 0.44; PRI, 0.46) (P = 0.78, n = 38). These
      results indicate that the signal contents of delay-period activities differ
      between the two subdivisions: TE mostly represents a sought target that is
      retrieved from long-term memory, while A36 in addition retains cue-stimulus that
      is transmitted from earlier visual areas.

PMID- 14656342
TI  - Tracking mouse visual pathways with WGA transgene.
AB  - By use of wheat germ agglutinin (WGA) cDNA as a transgene, we have succeeded in
      generating a transgenic mouse line in which the visual pathways can be accurately
      and reproducibly visualized. The WGA transgene was expressed in the retinal rod
      bipolar cells under the control of mouse L7 promoter. The transgene product, WGA
      protein, was transferred from the bipolar cells to the amacrine cells and the
      ganglion cells across synapses in the retinal neural circuitry and further
      conveyed along the optic nerve to the visual centers such as the suprachiasmatic
      nucleus, the lateral geniculate nucleus, the pretectal nucleus and the superior
      colliculus. By crossing the WGA-expressing transgenic mice with the retinal
      degeneration mutant mice, we analyzed change in the visual pathways by monitoring
      WGA immunoreactivity and found that the disorganization process of the visual
      pathways was relatively slow in spite of the rapid degeneration of the
      photoreceptor cells. Thus, this transgenic mouse line would provide a useful tool
      for analyzing phenotypic changes in the visual pathways of various mutant mice.

PMID- 14656344
TI  - Anti-allergic mattress covers in asthma: to do or not to do?

PMID- 14656345
TI  - Immunological differences between intrinsic and extrinsic types of atopic
      dermatitis.

PMID- 14656346
TI  - Mechanisms of severe asthma.
AB  - The mechanisms behind the development of severe asthma are poorly understood.
      However, these patients disproportionately consume healthcare resources related
      to asthma. Severe asthma may develop over time, or may develop shortly after
      onset of the disease. The genetic and environmental elements that may be most
      important in the development of severe disease are poorly understood.
      Physiologically, these patients often have air trapping and airway
      collapsibility. The pathology demonstrates a heterogeneity of findings, including
      continued eosinophilic inflammation, an apparently different pathology,
      structural changes likely to be remodelling related, and predominant distal
      disease. Treatment remains problematic and likely will remain so until a better
      understanding of this disease develops.

PMID- 14656347
TI  - Remodelling of the upper airways in allergic rhinitis: is it a feature of the
      disease?
AB  - The traditional viewpoint that inflammation, owing to a genetic T-helper type 2
      (Th2)-directed imbalance, is the cause of allergic rhinitis has meant that the
      potential coexistence of other genetic defects and the relevance of any airway
      remodelling changes to disease pathogenesis and persistence have received scant
      attention, and as such remain controversial areas. This is particularly so in
      view of the limited published work in this field, which has so far reported
      markedly conflicting findings. This review endeavours to outline what is known
      about the nature of the remodelling response within the upper airway in allergic
      rhinitis, in addition to highlighting specific areas where further research is
      warranted.

PMID- 14656348
TI  - Immunological effects of probiotics with special reference to lactobacilli.

PMID- 14656349
TI  - Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in
      children allergic to Parietaria pollen treated with inhaled fluticasone
      propionate.
AB  - BACKGROUND: Immunotherapy is a recognized treatment for allergic respiratory
      diseases. OBJECTIVE: To study the usefulness of immunotherapy in combination with
      optimal pharmacological therapy. METHODS: Thirty-eight children (8-14 years)
      suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly
      controlled by anti-allergic drugs treatment were selected. After randomization
      according to a double-blind placebo-controlled design they received active
      sublingual immunotherapy (15 children) or placebo (15 children) for 13 months
      combined with inhaled fluticasone twice a day during the pollen season. Eight
      children were taken as control, whereas all patients were instructed to take
      symptomatic drugs on need. Early and late skin response to the allergen were
      assessed in all patients before and after treatment. Drug and symptom scores, as
      well as visual analogue scores (VASs) and Parietaria pollen counts were assessed
      during the pollen season. RESULTS: Groups were well balanced for age, gender,
      early and late skin response before treatment. Four children dropped out, in one
      case in relationship with active sublingual immunotherapy (SLIT) administration.
      Chest and nose symptoms, as well as drug scores and VASs were significantly
      better in both the active or placebo SLIT+fluticasone (S+F) as compared to the
      control group (P between <0.001 and 0.043). Eye symptoms were significantly
      better in the active S+F group as compared to control (P=0.025). The VASs were
      significantly better in the active S+F group as compared to the placebo S+F group
      (P=0.037). The early skin response decreased significantly in the active S+F
      group (P<0.001), whereas the late skin response changed significantly in all
      groups, with an increase in the placebo+fluticasone group (P=0.019) and in the
      control group (P=0.037) and a decrease (P<0.0001) in the active S+F group.
      CONCLUSION: The clinical efficacy of S+F is equal to that of fluticasone alone,
      but the addition of SLIT has effects also on non-bronchial symptoms.

PMID- 14656350
TI  - A randomized controlled trial of mite allergen-impermeable bed covers in adult
      mite-sensitized asthmatics.
AB  - BACKGROUND: Mite-allergic patients with allergic disease should benefit from
      avoiding mite allergens. Many physicians, however, are yet to be convinced that
      allergen avoidance can make a significant contribution to asthma management in
      these patients. Many allergen-avoidance regimes include multiple measures of
      allergen reduction, but as mite exposure in the home is most likely to be
      greatest in bed dust, bedding is usually the first target for intervention.
      OBJECTIVE: This study selected adult patients considered to be most likely to
      benefit from avoiding mite allergens, namely diagnosed asthmatics, sensitized to
      house dust mites and exposed to mite allergen in their mattresses. Patients were
      randomized into a placebo-controlled trial of the use of allergen-impermeable bed
      covers for 12 months, without any other form of mite-reduction measures. METHODS:
      Adults with asthma were selected from general practices and asthma clinics in
      south-east London. Their serum IgE to mite allergens and allergen content of
      mattress dust samples were measured. Those with >0.70 kU/L mite-specific IgE and
      >2 microg/g Der p 1 were randomized into active or placebo treatments.
      Information was collected on allergic symptoms and medication use and quarterly
      peak flow diaries were kept throughout the trial. Dog or cat allergic patients
      were excluded if they had a pet at home to which they were sensitized. RESULTS:
      The mean decrease in microg/g Der p 1 was 25.7 (95% CI 8.9, 74.1) in the active
      group and 4.5 (95% CI 1.8, 11.5) in the placebo group. Der p 1 concentrations in
      the active and placebo groups at the end of the trial were not significantly
      different. There was no effect on peak flow or asthma symptoms in a simple
      comparison of the treatment and placebo groups. CONCLUSION: In this group of
      patients, mite allergen avoidance in the bed by the use of allergen-impermeable
      bedding alone cannot be recommended as an effective way of relieving asthma
      symptoms.

PMID- 14656351
TI  - Measurement of Dermatophagoides mite allergens on bedding and human skin
      surfaces.
AB  - BACKGROUND: The level of the Dermatophagoides mite group 1 (Der 1) allergens in
      reservoir dust has been used as an index of exposure in most studies. However,
      the mite allergen level in reservoir dust cannot directly reflect the personal
      exposure level. OBJECTIVE: We sought to develop a new method for quantifying the
      Der 1 allergens on bedding and human skin surfaces as an index of exposure to
      mite allergens. METHODS: Samples were obtained with a small adhesive tape from
      the forearm skin of 30 healthy volunteers and from their regularly used
      mattresses. The level of Der 1 allergens collected onto the adhesive tape was
      measured by a newly developed sensitive fluorometric ELISA for Der p 1 and Der f
      1. RESULTS: The Der 1 allergens could be detected in all the samples from bedding
      surfaces and in 28 of the 30 samples from skin surfaces. The Der 1 levels by
      adhesive tape sampling from the mattresses correlated with those by reservoir
      dust sampling. The sampling of the skin and bedding surface with adhesive tape
      correlated, but skin sampling did not correlate with reservoir sampling.
      CONCLUSION: The Der 1 allergens on bedding surfaces and on human skin surfaces
      could be quantified with a very simple sampling technique. The system developed
      in this study will provide a new tool for the assessment of mite allergen
      exposure in daily life.

PMID- 14656352
TI  - Repeated measurements of allergens and endotoxin in settled house dust over a
      time period of 6 years.
AB  - BACKGROUND: Studies investigating the effect of exposure to indoor allergens and
      endotoxin on human respiratory health usually take dust samples only at one
      single point of time and consider them to be representative for the indoor
      biocontaminant burden during a time period of several years. This singly measured
      biocontaminant concentration is related to adverse respiratory outcomes such as
      asthma, wheeze or others. OBJECTIVE: We analysed two repeated measurements of
      mite and cat allergens in mattress and living room floor dust as well as
      endotoxin concentrations in living room floor dust. The repeated samples were
      taken over a time period of about 6 years. We investigated the repeatability over
      time of their concentrations by determining correlation coefficients and
      computing within- and between-home variance components. METHODS: Our analysis was
      based on the population of a study on Indoor Factors and Genetics in Asthma
      (INGA) being carried out in 1995/96 and followed up in 2000/01. Complete data
      were available from 152 participants. RESULTS: The measured allergen
      concentrations were low and a considerable percentage of the values was below the
      limit of detection. The crude Spearman's rank correlation coefficients between
      the two measurements taken in 1995/96 and 2000/01 ranged from 0.32 to 0.61 for
      the dust mites allergens, from 0.21 to 0.44 for cat allergen and from 0.35 to
      0.51 for endotoxin. Correlations were higher if measurements were performed on
      the same floor or the same mattress at both sampling time-points. The within-home
      variance for all measured biocontaminant concentrations was of about the same
      order as the between-home variance. CONCLUSION: For studies like ours with low
      allergen and endotoxin concentrations, the repeatability of these concentrations
      over a time period as long as 6 years is low and a single measurement does not
      accurately reflect the true long-term exposure in the homes.

PMID- 14656353
TI  - Validation of an environmental exposure unit for controlled human inhalation
      studies with grass pollen in patients with seasonal allergic rhinitis.
AB  - BACKGROUND: There is an increasing need for allergen inhalation systems to
      perform basic clinical research and test anti-allergic drugs under well
      controlled conditions. This requires stability of environmental conditions like
      temperature and humidity, as well as allergen concentration and reproducible
      induction of allergic symptoms. OBJECTIVE: The aim of this study was to validate
      an environmental exposure unit for controlled human pollen inhalation studies in
      participants with seasonal allergic rhinitis. METHODS: Temperature, relative
      humidity, and air flow rate were kept constant with an air conditioning system.
      Pollen atmosphere was generated using a specially designed feeding system and
      monitored online by laser counter and offline using rotating rod samplers.
      Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and
      safety (lung function) parameters were evaluated at different pollen
      concentrations and repeated allergen challenges. RESULTS: Temperature, humidity,
      and air flow rate in the environmental exposure unit remained constant within a
      range of <2%. The spatial distribution and the temporal stability of the pollen
      concentration varied only slightly over 4 h (+/-10% and <4%, respectively). Dose
      dependent induction of allergic rhinitis symptoms, reduction in nasal air flow
      rate, and increase in nasal secretion were observed over time. These effects were
      reproducible from day to day. Lung function remained clinically normal at all
      concentrations and from day to day. CONCLUSIONS: Thus, pollen exposure in the
      environmental exposure unit is an effective, reproducible, safe, and suitable
      method for single-centre clinical studies on the efficacy of anti-allergic
      treatment or basic clinical research.

PMID- 14656354
TI  - Pollen counts in relation to the prevalence of allergic rhinoconjunctivitis,
      asthma and atopic eczema in the International Study of Asthma and Allergies in
      Childhood (ISAAC).
AB  - BACKGROUND: Although pollens are major allergens associated with allergic
      rhinoconjunctivitis and asthma, there is little information about the relative
      prevalence of these conditions in populations with different pollen exposures.
      OBJECTIVE: The purpose of this study was to investigate the relationship between
      pollen exposure and allergic symptoms among children in different countries.
      METHODS: An ecological analysis was conducted to see whether pollen exposure
      (pollen counts, and duration and severity of pollen seasons) is associated with
      symptoms of allergic rhinoconjunctivitis, asthma and atopic eczema in 28 centres
      within 11 countries (nine being in Europe). Data on the prevalence of symptoms in
      13-14-year olds were based on the responses to the written questionnaires from
      the International Study of Asthma and Allergies in Childhood (ISAAC). The
      analysis was adjusted for gross national product and mean annual relative
      humidity. RESULTS: There was little relationship between pollen exposure and
      symptom prevalence, except for a significant inverse association between grass
      pollen counts and lifetime prevalence of the symptoms of allergic rhinitis
      (P=0.03). Almost all the regression coefficients were negative. The associations
      were even weaker and all non-significant when the analyses were conducted within
      countries, using a random intercept fixed slope model, but there was still no
      evidence of a positive association between pollen exposure and symptoms.
      CONCLUSION: There is a weak but consistent tendency for the prevalence of
      allergic symptoms to be inversely associated with pollen exposure. This finding
      accords with evidence from several countries, suggesting that the prevalence of
      hayfever and asthma tends to be lower in rural than in urban areas, and lowest
      among people living on farms. Exposure to allergenic pollen in early life does
      not appear to increase the risk of acquiring symptoms of respiratory allergy, and
      may even give some protection against them.

PMID- 14656355
TI  - High-dose exposure to cat is associated with clinical tolerance--a modified Th2
      immune response?
AB  - BACKGROUND: Allergen-specific IgG4 antibodies, it is suggested, may be protecting
      against allergy development by blocking responses. Levels are proposed as a
      marker of modified Th2 response. OBJECTIVES: To assess the levels of IgE, IgG1
      and IgG4 antibodies to cat in relation to cat exposure, asthma and allergic
      diseases. METHODS: We studied a population-based sample of 412 schoolchildren of
      12-13 years of age. Parents of 402 children completed a questionnaire covering
      their child's medical history, the keeping of cats and other background data.
      Skin prick tests (SPTs) to common aeroallergens were performed in 371 of the
      children. Blood samples for the analyses of IgE, IgG1 and IgG4 antibodies were
      obtained from 309 of them. RESULTS: All children had an immune response to cat,
      predominantly of the IgG1 subclass. The levels of cat-specific IgG1 and IgG4, but
      not IgE, were high in children currently keeping a cat. Children with asthma had
      increased levels of cat-specific IgE and IgG1, and children with a positive SPT
      to cat also had increased IgG4. The presence of IgG4 was not associated with
      asthma or sensitization, unless there was a simultaneous production of IgE.
      Twenty-five percent of the children had an immune response with only IgG4, and no
      IgE antibodies to cat. This group of children had the highest frequency of cat
      keeping, but a similar prevalence of asthma and allergy as those with neither IgE
      nor IgG4 antibodies to cat. CONCLUSION: Cat-keeping was associated with a
      modified Th2 response, producing IgG4 but not IgE antibodies. This immune
      response was not associated with an increased risk of asthma or allergy. However,
      the IgG4 antibodies did not directly mediate any protective effect.

PMID- 14656356
TI  - Immune and airway effects of house dust mite aeroallergen exposures during
      postnatal development of the infant rhesus monkey.
AB  - BACKGROUND: The effect of chronic environmental aeroallergen exposure on the
      immune system and airways has not been experimentally defined in very young
      children. OBJECTIVE: The purpose of this study was to determine the
      immunophenotype of peripheral blood and airway leucocytes in the newborn rhesus
      macaque monkey, following recurrent aerosol exposure to house dust mite (HDM)
      (Dermatophagoides farinae). METHODS: A regimen of HDM aerosolization was
      initiated for 2 h per day, three times per week, starting when rhesus macaque
      monkeys were 1 week of age. All monkeys were inoculated with diptheria, tetanus,
      and acellular pertussis vaccine at 5 weeks of age to simulate human infant
      vaccination schedules. RESULTS: Following 8 weeks of HDM aeroallergen exposure,
      infant monkeys exhibited a significant reduction in the total peripheral blood
      lymphocyte numbers and a decreased frequency of peripheral blood CD4+ T
      lymphocytes with a CD45RA-'memory' immunophenotype. Lavage CD4+ T lymphocytes
      from HDM-exposed monkeys showed elevated expression of CD25, as well as an
      increase in CD45RA-/CD62L-/CD11ahigh immunophenotype. Eosinophils were more
      abundant within airways of HDM-exposed monkeys, accumulating maximally within the
      trachea. CONCLUSION: These data demonstrate the development of immunological
      responses following chronic inhalation of a common environmental allergen during
      postnatal maturation in the non-human primate.

PMID- 14656357
TI  - Characterization of recombinant cat albumin.
AB  - BACKGROUND: Indoor allergens derived from animals and mites often contribute to
      exacerbation of skin manifestations in atopic dermatitis (AD) patients.
      OBJECTIVE: To produce and characterize recombinant cat albumin, a cross-reactive
      animal allergen. METHODS: A complete cDNA coding for cat albumin was obtained by
      RT-PCR amplification from cat liver RNA. Recombinant cat albumin was expressed in
      Escherichia coli as hexahistidine-tagged protein, purified by nickel affinity
      chromatography and studied for IgE reactivity with sera from cat-allergic
      patients by ELISA and immunoblotting. Furthermore, CD203c expression of basophils
      from cat-allergic patients upon exposure to recombinant cat albumin was analysed.
      RESULTS: Recombinant cat albumin, a cross-reactive animal allergen sharing most
      IgE epitopes with its natural counterpart, was produced in E. coli. It was
      recognized preferentially by IgE from AD patients and elicited IgE-dependent
      basophil activation in sensitized patients. CONCLUSIONS: Recombinant cat albumin
      may be used as a paradigmatic tool to analyse mechanisms of allergen-triggered
      exacerbation of AD, for diagnostic and, perhaps for therapeutic purposes.

PMID- 14656358
TI  - Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen
      with significant homology to ribosomal inactivating proteins.
AB  - BACKGROUND: Patients suffering from allergic rhinoconjunctivitis and dyspnoea
      during summer may exhibit these symptoms after contact with flowers or dietary
      products of the elderberry tree Sambucus nigra. OBJECTIVE: Patients with a
      history of summer hayfever were tested in a routine setting for sensitization to
      elderberry. Nine patients having allergic symptoms due to elderberry and specific
      sensitization were investigated in detail. We studied the responsible allergens
      in extracts from elderberry pollen, flowers and berries, and investigated cross
      reactivity with allergens from birch, grass and mugwort. METHODS: Sera from
      patients were tested for IgE reactivity to elderberry proteins by one-dimensional
      (1D) and 2D electrophoresis/immunoblotting. Inhibition studies with defined
      allergens and elderberry-specific antibodies were used to evaluate cross
      reactivity. The main elderberry allergen was purified by gel filtration and
      reversed-phase HPLC, and subjected to mass spectrometry. The in-gel-digested
      allergen was analysed by the MS/MS sequence analysis and peptide mapping. The N
      terminal sequence of the predominant allergen was analysed. RESULTS: 0.6% of 3668
      randomly tested patients showed positive skin prick test and/or RAST to
      elderberry. IgE in patients' sera detected a predominant allergen of 33.2 kDa in
      extracts from elderberry pollen, flowers and berries, with an isoelectric point
      at pH 7.0. Pre-incubation of sera with extracts from birch, mugwort or grass
      pollen rendered insignificant or no inhibition of IgE binding to blotted
      elderberry proteins. Specific mouse antisera reacted exclusively with proteins
      from elderberry. N-terminal sequence analysis, as well as MS/MS spectrometry of
      the purified elderberry allergen, indicated homology with ribosomal inactivating
      proteins (RIPs). CONCLUSION: We present evidence that the elderberry plant S.
      nigra harbours allergenic potency. Independent methodologies argue for a
      significant homology of the predominant 33.2 kDa elderberry allergen with
      homology to RIPs. We conclude that this protein is a candidate for a major
      elderberry allergen with designation Sam n 1.

PMID- 14656359
TI  - Interleukin-4 and -13 expression is co-localized to mast cells within the airway
      smooth muscle in asthma.
AB  - BACKGROUND: Airway smooth muscle infiltration by mast cells is a feature of
      asthma and not eosinophilic bronchitis. In asthma, Th2 cytokines have been
      implicated as playing a critical role in the development of airway inflammation
      and hyper-responsiveness. Whether inflammatory cells within the airway smooth
      muscle release these cytokines is unknown. METHODS: We have undertaken a
      comparative immunohistochemical study in bronchial biopsies from 14 subjects with
      asthma, 10 with eosinophilic bronchitis and eight normal controls recruited from
      two centres. RESULTS: The median number of IL-4+ cells/mm2 smooth muscle was
      significantly higher in subjects with asthma than eosinophilic bronchitis and
      normal controls for both the anti-IL-4 mAb 3H4 (2.4, 0, 0, respectively; P=0.001)
      and anti-IL-4 mAb 4D9 (1.6, 0, 0, respectively; P=0.02). There were no group
      differences in the number of IL-5+ cells (P=0.31). In six subjects with asthma,
      IL-13 expression by cells within the airway smooth muscle was studied. The median
      (range) of IL-13+cells was 2 (0.9-2.7). Ninety-four percent of the cells
      expressing IL-4 (3H4), 92% of those expressing IL-4 (4D9) and 100% expressing IL
      13 in the airway smooth muscle were mast cells. Fifty-five percent of the mast
      cells within the airway smooth muscle co-localized to IL-4 (3H4), 29% to IL-4
      (4D9) and 17% to IL-13. CONCLUSIONS: In asthma, IL-4+ and IL-13+ cells were
      present within the airway smooth muscle and were expressed predominantly by mast
      cells, suggesting that IL-4 and IL-13 may play an important role in mast cell
      airway smooth muscle interactions.

PMID- 14656360
TI  - Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs.
      extrinsic atopic dermatitis patients using semiquantitative RT-PCR.
AB  - BACKGROUND: A small subgroup of atopic dermatitis (AD) patients with normal serum
      IgE levels and without specific IgE sensitization has been termed 'intrinsic type
      of AD' (ADi) as a counterpart to the term 'extrinsic type of AD' (ADe). However,
      there are neither molecular markers nor clinically diagnostic tools for
      distinguishing between ADi and ADe. OBJECTIVE: The present studies were
      undertaken to clarify the pathogenesis and in vivo cytokine micromilieu of ADi
      patients in comparison with ADe patients. METHODS: We used semiquantitative RT
      PCR to investigate the expression of various cytokines and assessed the tissue
      eosinophil counts in skin biopsies from both types of AD patients. RESULTS:
      Although there was no significant difference of cellular infiltrates in the
      lesional skin between ADe and ADi patients, ADe had significantly increased
      tissue eosinophilia than ADi. Based on our RT-PCR, the expression patterns of
      cytokines could be categorized into four groups. The first group includes IL-5,
      IL-13, and IL-1beta, whose levels of mRNA expression were higher in both types of
      AD patients than non-atopic (NA) subjects, while ADe patients had even higher
      levels than ADi patients. The second group includes interferon-gamma (IFN-gamma),
      IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL
      10, whose levels of mRNA expression were elevated in both types of AD patients
      without differences between ADe and ADi patients. The third group includes tumour
      necrosis factor-alpha (TNF-alpha), whose mRNA expression was more decreased in
      both types of AD patients than NA, and the fourth group includes IL-6 and
      transforming growth factor-beta (TGF-beta), which did not show any differences
      among the three groups. CONCLUSION: These current data demonstrate that the
      expressions of cytokines IL-5, IL-13, and IL-1beta mRNA and the number of dermal
      infiltrating eosinophils are increased in ADe patients compared with ADi
      patients.

PMID- 14656361
TI  - Suspected tartrazine-induced acute urticaria/angioedema is only rarely
      reproducible by oral rechallenge.
AB  - BACKGROUND: Tartrazine has been frequently linked to several diseases. However, a
      cause-and-effect role for tartrazine in these illnesses, especially in urticaria,
      has not always been established. OBJECTIVE: The aim of this study is to determine
      the incidence of intolerance to tartrazine among subjects who experienced an
      acute episode of urticaria/angioedema following the ingestion of a meal or a
      product containing this substance. METHODS: This was a retrospective study based
      on analysis of data of patients reported to have experienced episodes of
      urticaria and/or angioedema after ingesting meals or products containing
      tartrazine. At the first visit to the outpatients clinic, a careful anamnesis had
      been taken. Patients had then been submitted to the following diagnostic tests:
      IgE tests to common inhalant allergens and food allergens and a double-blind
      placebo-controlled challenge with tartrazine. RESULTS: A total of 102 subjects
      were enrolled in the study: 19 (18.6%) showed at least one relevant positive
      reaction to an IgE test for food allergy. Only one subject (1%) had reactions
      after ingestion of 5 mg of tartrazine, given on day 5. She did not have adverse
      reactions to placebo. CONCLUSION: This study shows that the percentage of acute
      urticaria and/or angioedema induced by tartrazine is very low (1%). In view of
      our results, we suggest that all physicians with patients who have suffered
      adverse reactions that could be attributed to tartrazine should also carefully
      evaluate other possible causes.

PMID- 14656362
TI  - Anaphylaxis from topical bovine thrombin (Thrombostat) during haemodialysis and
      evaluation of sensitization among a dialysis population.
AB  - BACKGROUND: Topical bovine thrombin (TBT) is used as a topical haemostatic agent
      in haemodialysis (HD) units and for surgical procedures. It has caused allergic
      reactions during surgical procedures, but no previous cases have been reported
      with dialysis usage. OBJECTIVE: A case is reported of anaphylaxis due to TBT in
      an HD patient. This led to a determination of whether HD patients exposed to TBT
      develop specific IgE and IgG antibodies to TBT and an assessment of the frequency
      of allergic symptoms in HD patients as compared with peritoneal dialysis (PD)
      patients. METHODS: A cross-sectional study of 100 HD and 52 PD patients was
      performed using a questionnaire to determine allergic symptoms. An ELISA assay
      was developed to determine TBT-specific IgE and IgG serum antibodies among HD
      patients. HD patients without TBT exposure and age- and gender-matched blood
      donors served as controls. RESULTS: Allergic symptoms temporally related to
      dialysis reported by a questionnaire were significantly more frequent for HD
      patients than for PD patients: rhinoconjuctivitis 11% vs. 2%, asthma symptoms 20%
      vs. 6%, urticaria 23% vs. 8% (P values <0.05). Positive TBT-specific IgE and IgG
      antibodies were more frequent among 65 exposed HD patients (28% for IgE and 26%
      for IgG) than for controls (4% and 9%), P<0.05. CONCLUSIONS: Results indicate the
      potential for sensitization and clinical allergic responses to beef thrombin when
      used for haemostasis in HD and suggest that other haemostatic methods should be
      considered.

PMID- 14656363
TI  - Heterogeneity of FeNO response to inhaled steroid in asthmatic children.
AB  - BACKGROUND: Nitric oxide in exhaled air is regarded as an inflammation marker,
      and may be used to monitor the anti-inflammatory control from inhaled
      corticosteroids (ICSs). However, this response to ICSs exhibits a heterogeneous
      pattern. OBJECTIVE: The study aimed to describe the independent variables
      associated with the heterogeneity in the response of exhaled nitric oxide to
      ICSs. METHODS: Exhaled nitric oxide (FeNO), lung function, bronchial hyper
      responsiveness (BHR), specific IgE to common inhalant allergens, blood
      eosinophils, other atopic manifestations and variants in nitric oxide synthethase
      1 (NOS1) gene were studied in a double-blind, placebo-controlled crossover
      comparison of budesonide (BUD) Turbohaler 1600 mcg daily vs. placebo in asthmatic
      schoolchildren. RESULTS: Forty children were included in the study from a
      screening of 184 asthmatic children with moderately persistent asthma, well
      controlled on regular BUD 400 mcg daily: 20 children with normal FeNO and 20 with
      raised FeNO. FeNO, BHR and forced expiratory volume in 1 s improved significantly
      after BUD 1600 mcg (BUD1600). However, FeNO after ICS treatment exhibited a
      Gaussian distribution and FeNO was significantly raised in 15 children. Allergy
      and BHR, but none of the other independent variables under study were
      significantly related to FeNO after BUD1600. CONCLUSION: Exhaled nitric oxide
      exhibited a heterogeneous response to ICS in asthmatic schoolchildren. Allergy
      and BHR were driving FeNO level independently of high-dose steroid treatment.
      This should be considered when using FeNO for steroid dose titration and
      monitoring of ICS anti-inflammatory control in asthmatic children.

PMID- 14656364
TI  - Effect of montelukast pretreatment on inducible nitric oxide synthase mRNA
      expression in the lungs of antigen-challenged allergic mice.
AB  - BACKGROUND: Growing evidence suggests that inducible nitric oxide synthase (iNOS)
      is the main source of the high output of exhaled nitric oxide (NO) in asthma.
      Treatment of asthmatic patients with glucocorticoids reduces high levels of
      exhaled NO mainly by inhibiting the transcription of iNOS. A similar reduction in
      exhaled NO was recently observed in patients treated with the leukotriene
      receptor antagonists, but the exact interaction between these drugs and iNOS
      remains obscure. OBJECTIVE: The purpose of this study was to evaluate the effect
      of a leukotriene receptor antagonist, montelukast, on the expression and activity
      of iNOS in a murine model of allergic asthma. METHODS: Twenty-four BALB/c mice
      were sensitized to OVA and were equally divided into 3 groups (Groups 1-3). Eight
      additional mice were sham sensitized and served as a negative control group
      (Group 4). Group 1 received montelukast 1 mg/kg/day in their drinking water,
      Group 2 received dexamethasone 1 mg/kg/day in their drinking water and Groups 3
      and 4 received plain tap water. After 1 week, the animals were challenged by
      inhalation of OVA and, 3 h later, they were killed and their lung cells were
      isolated by enzymatic tissue digestion. NO generation was measured by a Griess
      assay, and iNOS mRNA was studied by RT-PCR. RESULTS: A significant increase in
      iNOS mRNA expression and in NO generation was evident after allergen challenge
      compared with the controls. Pretreatment with montelukast mildly decreased NO
      production without producing a concomitant significant decrease in iNOS mRNA
      expression. CONCLUSION: Unlike pretreatment with glucocorticoids, we failed to
      find compelling evidence for a major role for montelukast treatment in the
      modulation of iNOS mRNA in a murine model of acute asthma.

PMID- 14656369
TI  - Mechanisms of NH4+ and NH3 transport during hypokalemia.
AB  - Along the collecting duct, secretion of ammonium (NH) is thought to occur through
      active H+ secretion in parallel with the non-ionic diffusion of ammonia (NH3).
      Thus NH3 is secreted into the collecting duct lumen down its concentration
      gradient. Moreover, the low NH permeability and high NH3 permeability observed in
      collecting duct epithelia minimizes back diffusion of NH. In general, an increase
      in the NH3 concentration gradient between the interstitium and the collecting
      duct lumen correlates with increased NH secretion. However, our laboratory and
      others have shown an important role of direct NH transport by the Na,K-ATPase. As
      K+ and NH compete for a common extracellular binding site on the Na,K-ATPase,
      reduced interstitial K+ concentration, such as during hypokalemia, augments NH
      uptake. Na,K-ATPase-mediated NH uptake provides an important source of H+ for net
      acid secretion during hypokalemia and contributes to the increase in NH excretion
      and metabolic alkalosis observed in this treatment model.

PMID- 14656365
TI  - Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde
      in guinea-pigs in vivo.
AB  - BACKGROUND: Indoor formaldehyde (FA) might worsen allergies and be an underlying
      factor for the increasing incidence and severity of asthma; the exact mechanism,
      however, remains unclear. OBJECTIVE: The present study examined the effects of
      repeated exposure to FA on methacholine- and antigen-induced bronchoconstriction
      in guinea-pigs in vivo. METHODS: First, non-sensitized guinea-pigs were
      transnasally treated with 0.1 or 1.0% FA or saline three times a week for 6
      weeks, and increasing concentrations of methacholine (50, 100, and 200 microg/mL)
      were inhaled at 5-min intervals. Second, guinea-pigs pre-treated with transnasal
      administration of FA or saline using the same protocol were passively sensitized
      with anti-ovalbumin (OA) serum 7 days before antigen challenge. Third, guinea
      pigs were actively sensitized with OA and pre-treated with transnasal
      administration of FA or saline using the same protocol. The lateral pressure of
      the tracheal tube (Pao) was measured under anesthesia and artificial ventilation.
      RESULTS: The antigen-induced increase in Pao in actively sensitized guinea-pigs
      was significantly potentiated by FA exposure in a dose-dependent manner. The dose
      response curve of the methacholine-induced increase in Pao in non-sensitized
      guinea-pigs or of the antigen-induced increase in Pao in passively sensitized
      guinea-pigs was not altered by FA exposure. Transnasal administration of FA
      significantly increased the serum anti-OA homocytotropic antibody titre (IgG) as
      measured by the passive cutaneous anaphylaxis reaction in actively sensitized
      guinea-pigs. CONCLUSION: The results suggest that repeated exposure to FA worsens
      allergic bronchoconstriction through enhancing antigen sensitization.

PMID- 14656370
TI  - Renal and hepatic expression of the ammonium transporter proteins, Rh B
      Glycoprotein and Rh C Glycoprotein.
AB  - A family of ammonium transporter proteins was recently identified. Members of
      this family, Rh B Glycoprotein (RhBG) and Rh C Glycoprotein (RhCG) are expressed
      in the kidney and the liver, important tissues for ammonium metabolism.
      Immunohistochemical studies demonstrate basolateral RhBG immunoreactivity in the
      connecting segment (CNT) and collecting ducts, but not in the proximal tubule or
      the loop of Henle. Colocalization with thiazide sensitive cotransporter and
      carbonic anhydrase II confirms expression in the CNT, initial collecting tubule
      (ICT), and throughout the collecting duct. Colocalization with AE1 and pendrin
      demonstrates expression is greatest in A-type intercalated cells in the cortical
      collecting duct (CCD), outer medullary collecting duct (OMCD) and inner medullary
      collecting duct (IMCD), present in the CCD principal cell, and not detectable in
      either pendrin-positive CCD intercalated cells or in non-intercalated cells in
      the OMCD and IMCD. RhCG immunoreactivity has a similar axial distribution as
      RhBG. However, RhCG immunoreactivity is apical, and is detectable in all CCD and
      outer stripe of OMCD cells. The liver, a second organ involved in ammonia
      metabolism, also expresses both RhBG and RhCG. Basolateral RhBG immunoreactivity
      is present in the perivenous hepatocyte, but is not present in either the
      periportal or mid-zonal hepatocyte. Hepatic RhCG mRNA is expressed at lower
      levels than RhBG, and RhCG protein is detected in bile duct epithelium. These
      findings indicate that RhBG and RhCG are involved in at least two organs that
      transport ammonia, and that they are located in sites where they are likely to
      mediate important roles in ammonia transport.

PMID- 14656371
TI  - Novel Ca2+ signalling mechanisms in vascular myocytes: symposium overview.
AB  - This commentary presents the proceedings of the symposium sponsored by
      Cardiovascular Section of American Physiological Society in San Diego, CA on 12
      April 2003. The major focus of this symposium was on the actions and
      physiological relevance of several novel Ca2+ signalling mechanisms in vascular
      smooth muscle (VSM) cells. Five important topics were presented in this symposium
      including the discovery and roles of cyclic ADP-ribose (cADPR) and nicotinic acid
      adenine dinucleotide phosphate (NAADP) in mediating Ca2+ release, Ca2+ sparks and
      activation of plasma membrane KCa channels in VSM cells, the role of cADPR
      mediated activation of ryanodine receptors in the control of vascular tone, the
      role of [Ca2+]i in mechanotransduction in the arterioles, and interactions of
      mitochondrial Ca2+ release and SR Ca2+ mobilization. The purpose of this
      symposium was to promote discussions and exchange of ideas between scientists
      with interests in Ca2+ signalling mechanisms and those with interests in vascular
      physiology and pharmacology. The cross-fertilization of ideas is expected to
      greatly advance our understanding of the physiological and pharmacological
      relevance of these new Ca2+ signalling mechanisms.

PMID- 14656372
TI  - Myocardial vasoactive intestinal peptide and fibrosis induced by nitric oxide
      synthase inhibition in the rat.
AB  - AIMS: In both normotensive and hypertensive rats, the degree of myocardial
      fibrosis is inversely correlated with the concentration of vasoactive intestinal
      peptide (VIP) in the myocardium. Treatment with nitric oxide (NO) synthase
      inhibitors also causes myocardial fibrosis. In this study, we sought to determine
      whether the myocardial fibrosis induced by treatment with the NO synthase
      inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) was also associated with
      depletion of VIP in the myocardium. METHODS: Male Wistar Kyoto (WKY) and
      spontaneous hypertensive rats (SHR) rats treated with l-NAME were randomized to
      low, intermediate or high salt content diets. After 4 weeks, the hearts were
      harvested, the degree of fibrosis quantified and VIP concentration measured.
      RESULTS: In WKY, systolic blood pressure increased with increasing dietary sodium
      (P < 0.05). Myocardial fibrosis also increased with increasing dietary sodium (P
      < 0.005). Myocardial VIP concentration decreased with increasing dietary sodium
      (P < 0.025). In contrast, in the SHR treated with l-NAME, systolic blood pressure
      increased but the increase was not affected by sodium intake. Further, myocardial
      fibrosis and myocardial VIP were unchanged by increased dietary sodium. Higher
      doses of l-NAME in the SHR did not increase the systolic blood pressure, increase
      the degree of myocardial fibrosis or decrease the myocardial concentration of
      VIP. These differences in myocardial VIP concentration may reflect differing
      effects of l-NAME on VIP metabolism, as l-NAME increased VIP metabolism in the
      WKY (P < 0.05) but did not change VIP metabolism in the SHR. CONCLUSIONS: We
      conclude that depletion of VIP in the myocardium is associated with increasing
      myocardial fibrosis in l-NAME treated WKY. As VIP depletion occurs in other
      models of myocardial fibrosis, it appears to be a common mechanism. Myocardial
      VIP depletion may therefore be a new and important factor in the pathogenesis of
      cardiac fibrosis.

PMID- 14656373
TI  - Non-invasive assessment of cardiac output during exercise in healthy young
      humans: comparison between Modelflow method and Doppler echocardiography method.
AB  - AIMS: The Modelflow method can estimate cardiac output from arterial blood
      pressure waveforms using a three-element model of aortic input impedance (aortic
      characteristic impedance, arterial compliance, and systemic vascular resistance).
      We tested the reliability of a non-invasive cardiac output estimation during
      submaximal exercise using the Modelflow method from finger arterial pressure
      waveforms collected by Portapres in healthy young humans. METHODS: The Doppler
      echocardiography method was used as a reference method. Sixteen healthy young
      subjects (nine males and seven females) performed a multi-stage cycle ergometer
      exercise at an intensity corresponding to 70, 90, 110 and 130% of their
      individual ventilatory threshold for 2 min each. The simultaneous estimation of
      cardiac output (15 s averaged data) using the Modelflow and Doppler
      echocardiography methods was performed at rest and during exercise. RESULTS AND
      CONCLUSION: The Modelflow-estimated cardiac output correlated significantly with
      the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P <
      0.0001) and the SE of estimation was 1.93 L min-1. Correlation coefficients in
      each subject ranged from 0.91 to 0.98. Although the Modelflow method
      overestimated cardiac output, the errors between two estimates were not
      significantly different among the exercise levels. These results suggest that the
      Modelflow method using Portapres could provide a reliable estimation of the
      relative change in cardiac output non-invasively and continuously during
      submaximal exercise in healthy young humans, at least in terms of the relative
      changes in cardiac output.

PMID- 14656374
TI  - Antisecretory factor peptide derivatives specifically inhibit [3H]-gamma-amino
      butyric acid/36Cl- out-->in permeation across the isolated rabbit Deiters'
      neuronal membrane.
AB  - AIMS: Antisecretory factor (AF) is a 41-kDa protein, its main function being the
      regulation of intestinal ion/water transport, but it also inhibits chloride and
      gamma-amino-butyric acid transport across nerve cell membranes. The present
      experiments were designed to evaluate whether the same AF peptide sequence
      mediates the permeability effects seen at the nerve cell membrane and in the rat
      small intestine. METHODS: Four peptides were prepared by the solid phase
      technique with sequences derived from positions 1-51 of the full-length
      antisecretory factor AF and tested on nerve cell membranes isolated from rabbit
      Dieter cells. RESULTS: AF peptides containing the active 36-51 peptide exerted a
      blocking effect of the out-->in permeation of 36Cl- as well as of [3H]-gamma
      amino-butyric acid. The minimal dose causing inhibition, however, varied between
      10(-11) m (AF10) and 10(-7) m (AF13). The most potent peptides have been shown
      previously to be active in inhibiting experimental diarrhoea in vivo in small
      intestinal ligated loops in rats. The non-active sequence AF23-32 did not inhibit
      any of the two permeation markers in vitro, a result which supports the lack of
      activity found also in vivo. CONCLUSION: The results suggest that AF, or AF
      derivatives, counteract intestinal hypersecretion by blocking anion permeation
      across large anionic pores. Such a blocking effect could also influence the
      generation of action potentials in enteric nerve cells controlling the intestinal
      water and ion transport system.

PMID- 14656375
TI  - Effect of alpha-trinositol on secretion induced by Escherichia coli ST-toxin in
      rat jejunum.
AB  - AIM: d-myo-inositol-1,2,6-trisphosphate (alpha-trinositol, PP56), is a synthetic
      isomer of the intracellular second messenger, d-myo-inositol-1,4,5
      trisphospahate. The pharmacological actions of alpha-trinositol include potent
      anti-inflammatory properties and inhibition of the secretion induced by cholera
      toxin and obstructive ileus. In the present study, we investigated whether alpha
      trinositol was able to influence the secretion induced by heat-stable ST-toxin
      from Escherichia coli in the rat jejunum. METHODS: A midline abdominal incision
      was performed in anaesthetized male Sprague-Dawley rats and a 6-7 cm long jejunal
      segment was isolated with intact vascular supply and placed in a chamber
      suspended from a force displacement transducer connected to a Grass(R) polygraph.
      Intestinal net fluid transport was continuously monitored gravimetrically.
      Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen
      and left there for the rest of the experiment. When a stable secretion was
      observed, alpha-trinositol (60 mg kg-1 h-1) or saline were infused during 2 h,
      followed by a 2-h control period. RESULTS: alpha-Trinositol induced a significant
      (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h
      after infusion had stopped. The agent also moderately increased (P < 0.05) net
      fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart
      rate (P < 0.001) were reduced by alpha-trinositol. CONCLUSION: The inhibition by
      alpha-trinositol of ST-toxin induced intestinal secretion is primarily secondary
      to inhibition of secretory mechanisms and only to lesser extent due to increased
      absorption. The detailed mechanisms of action have not been clarified but may
      involve suppression of inflammation possibly by means of cellular signal
      transduction.

PMID- 14656376
TI  - Oestrogen receptor beta is expressed in adult human skeletal muscle both at the
      mRNA and protein level.
AB  - AIM: There are two known oestrogen receptors (ER), oestrogen receptor alpha
      (ERalpha) and the recently cloned oestrogen receptor beta (ERbeta). ERalpha mRNA
      has been detected in mouse, rat, bovine and human skeletal muscle. ERbeta mRNA
      has been detected in bovine skeletal muscle. To our knowledge, no study has
      investigated the expression of oestrogen receptor beta in human skeletal muscle.
      Therefore, the primary aim of the present investigation was to study ERbeta mRNA
      and protein expression in human skeletal muscle. In addition the ERalpha
      expression was also studied. METHODS: Muscle biopsies were taken from vastus
      lateralis in six healthy adults (three women and three men). mRNA expression was
      detected with real-time PCR (TaqMan) and protein localization by
      immunohistochemistry. RESULTS: A clear expression of ERalpha and ERbeta mRNA was
      seen in skeletal muscle in all subjects. The ERalpha mRNA expression was 180 fold
      higher compared with that of ERbeta mRNA. Immunohistochemistry demonstrated
      positive staining for ERbeta, but not for ERalpha, with localization to the
      nuclei of skeletal muscle fibres. On average, 70% of all nuclei were ERbeta
      positive. CONCLUSION: The present study shows for the first time ERbeta mRNA and
      protein expression in human skeletal muscle tissue in both males and females.

PMID- 14656377
TI  - Human motor compensations for thixotropy-dependent changes in resting wrist joint
      position after large joint movements.
AB  - AIM: Resting tension of relaxed skeletal muscle fibres held at a given length
      varies with the immediate previous history of length changes and contractions.
      The primary aim of this study was to explore the motor control consequences of
      this history-dependency in healthy subjects. METHODS: Angular position and
      passive torque were recorded from the intact wrist joint. Integrated surface
      electromyography (IEMG) was recorded from wrist extensor and flexor muscles.
      RESULTS: In relaxed subjects, wrist joint position was displaced towards
      dorsiflexion after a single high-amplitude dorsiflexion movement combined with a
      strong flexor/extensor co-contraction (dorsiflexion conditioning), whereas after
      volarflexion conditioning there was a shift towards volarflexion. These after
      effects could be abruptly cancelled by short periods ( approximately 5 s) of
      rapid flapping hand movements or forceful isometric co-contractions, findings
      indicative of muscle thixotropy. The IEMG-evaluated motor after-effects were as
      follows. A slowly subsiding wrist flexor contraction was needed to restore and
      maintain the original resting wrist position after dorsiflexion conditioning
      whereas a slowly subsiding extensor contraction was needed for the same goal
      after volarflexion conditioning. Furthermore, ongoing wrist extensor IEMG
      activity required to actively hold the wrist in a moderate dorsiflexed position
      or to resist a constant volar torque at resting position was temporarily reduced
      after dorsiflexion conditioning and enhanced (not significantly) after
      volarflexion conditioning. CONCLUSION: The results provide evidence that during
      voluntary maintenance of a desired wrist joint position the motor commands to the
      position-holding muscles are unconsciously adjusted to compensate for thixotropy
      dependent variations in the resting tension of the muscles.

PMID- 14656378
TI  - Increased tissue survival in experimental skin flaps in mast cell-deficient rats.
AB  - AIM: The role of mast cells and their principal mediator, histamine, in surgical
      skin flap survival was investigated using mast cell-deficient (Ws/Ws); their
      congenic littermates wild-type (+/+), and Wistar rats. METHODS: A standardized
      dorsal skin flap was raised and sutured back into position, and 6 days later the
      percentage of flap survival was assessed. Moreover, endogenous histamine
      concentration in the dorsal skin during the surgical preparation was determined
      using in vivo microdialysis technique together with high performance liquid
      chromatography-fluorometry. Accumulation of skin flap myeloperoxidase (MPO)
      (reflecting leucocyte recruitment) was determined spectrophotometrically.
      RESULTS: The experimental skin flaps in genetically mast cell-deficient rats
      exhibited increased tissue survival and showed little accumulation of MPO and
      rather low and stable level of histamine output in comparison with skin flaps in
      the wild-type (+/+) littermates or normal Wistar rats. Antihistamine treatment
      inhibited but did not prevent leucocyte recruitment in the skin flaps post
      surgery in +/+ and Wistar rats. CONCLUSION: It is suggested that mast cell
      derived histamine plays an important role in leucocyte recruitment in skin flaps.
      However, mast cell-independent factors should be taken into consideration and
      needs further investigation as even in mast cell-deficient animals there was some
      accumulation of leucocytes and tissue necrosis in the skin flaps post-surgery.

PMID- 14656379
TI  - Gross Domestic Product (GDP) and productivity of schizophrenia trials: an
      ecological study.
AB  - BACKGROUND: The 5000 randomised controlled trials (RCTs) in the Cochrane
      Schizophrenia Group's database affords an opportunity to research for variables
      related to the differences between nations of their output of schizophrenia
      trials. METHODS: Ecological study--investigating the relationship between four
      economic/demographic variables and number of schizophrenia RCTs per country. The
      variable with closest correlation was used to predict the expected number of
      studies. RESULTS: GDP closely correlated with schizophrenia trial output, with
      76% of the total variation about the Y explained by the regression line (r =
      0.87, 95% CI 0.79 to 0.92, r2 = 0.76). Many countries have a strong tradition of
      schizophrenia trials, exceeding their predicted output. All nations with no
      identified trial output had GDPs that predicted zero trial activity. Several
      nations with relatively small GDPs are, nevertheless, highly productive of
      trials. Some wealthy countries seem either not to have produced the expected
      number of randomised trials or not to have disseminated them to the English
      speaking world. CONCLUSIONS: This hypothesis-generating study could not
      investigate causal relationships, but suggests, that for those seeking all
      relevant studies, expending effort searching the scientific literature of
      Germany, Italy, France, Brazil and Japan may be a good investment.

PMID- 14656382
TI  - Individualized therapy for non-small cell lung cancer.

PMID- 14656381
TI  - FGF signaling inhibits the proliferation of human myeloma cells and reduces c-myc
      expression.
AB  - BACKGROUND: Multiple myeloma is a cancer of antibody producing plasma cells whose
      etiology is unknown. FGF signaling has been implicated in myeloma pathogenesis
      but its precise role remains unclear. RESULTS: Here, we investigate the
      biochemical and phenotypic consequences of FGF stimulation in several different
      human myeloma cell lines. We find that FGF signaling inhibits cell cycle
      progression in two lines and surprisingly, reduces the expression of c-myc while
      turning on c-fos. In several other lines, FGF signaling does not affect
      proliferation rate, including cells harboring translocated FGF Receptor 3. When
      cells are presented with a growth arrest signal, FGF addition induces cell death.
      CONCLUSIONS: By showing that FGF signaling inhibits mitogenesis and induces
      apoptosis, we demonstrate novel effects of activating this ubiquitous signaling
      pathway in multiple myeloma.

PMID- 14656380
TI  - Enhanced beta2-adrenergic receptor (beta2AR) signaling by adeno-associated viral
      (AAV)-mediated gene transfer.
AB  - BACKGROUND: Beta2-adrenergic receptors (beta2AR) play important regulatory roles
      in a variety of cells and organ systems and are important therapeutic targets in
      the treatment of airway and cardiovascular disease. Prolonged use of beta
      agonists results in tolerance secondary to receptor down-regulation resulting in
      reduced therapeutic efficiency. The purpose of this work is to evaluate the
      signaling capabilities of the beta2AR expressed by a recombinant adeno-associated
      viral (AAV) vector that also included an enhanced green fluorescent protein
      (EGFP) gene (AAV-beta2AR/EGFP). RESULTS: By epifluorescence microscopy,
      approximately 40% of infected HEK 293 cells demonstrated EGFP expression. beta2AR
      density measured with [3H]dihydroalprenolol ([3H]DHA) increased either 13- or 77
      fold in infected cells compared to mock infected controls depending on the
      culture conditions used. The [3H]DHA binding was to a single receptor population
      with a dissociation constant of 0.42 nM, as would be expected for wild-type
      beta2AR. Agonist competition assays with [3H]DHA showed the following rank order
      of potency: isoproterenol>epinephrine> norepinephrine, consistent with beta2AR
      interaction. Isoproterenol-stimulated cyclic AMP levels were 5-fold higher in
      infected cells compared to controls (314 +/- 43 vs. 63.4 +/- 9.6 nmol/dish; n =
      3). Receptor trafficking demonstrated surface expression of beta2AR with vehicle
      treatment and internalization following isoproterenol treatment. CONCLUSIONS: We
      conclude that HEK 293 cells infected with AAV-beta2AR/EGFP effectively express
      beta2AR and that increased expression of these receptors results in enhanced
      beta2AR signaling. This method of gene transfer may provide an important means to
      enhance function in in vivo systems.

PMID- 14656384
TI  - Individualizing chemotherapy for treatment of non-small-cell lung cancer based on
      genetic profiling of tumors and patients.

PMID- 14656383
TI  - Highlights from: 37th Annual American Society of Clinical Oncology Meeting San
      Francisco, CA, May 12-15, 2001.

PMID- 14656385
TI  - Granulocyte macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor
      vaccines (GVAX) in non-small-cell lung cancer.

PMID- 14656386
TI  - ZD1839 (Iressa) in non-small-cell lung cancer.
AB  - The epidermal growth factor receptor (EGFR) signaling pathway plays an important
      role in a number of processes that are key to tumor progression, including cell
      proliferation, angiogenesis, metastatic spread, and inhibition of apoptosis. EGFR
      is expressed or overexpressed in non-small-cell lung cancer (NSCLC), and EGFR
      mediated growth has been associated with advanced disease and poor prognosis in
      NSCLC patients. ZD1839 (Iressa) is an orally active, selective EGFR-tyrosine
      kinase inhibitor that blocks EGFR signal transduction. In preclinical studies
      using NSCLC cell lines, ZD1839 has been shown to inhibit tumor cell growth. In
      addition, ZD1839, as monotherapy and in combination with commonly used cytotoxic
      agents, has produced growth delay in NSCLC human xenografts. Preliminary results
      from phase I trials in patients with advanced disease have shown that ZD1839 has
      excellent bioavailability, an acceptable tolerability profile, and promising
      clinical activity in patients with a variety of tumor types, particularly in
      NSCLC. ZD1839 is currently in phase III clinical development for the treatment of
      advanced NSCLC.

PMID- 14656387
TI  - The relevance of the revised version of the international lung cancer staging
      system for non-small-cell lung cancer treated with radiotherapy.
AB  - In 1997, the International Union Against Cancer (UICC) introduced a new version
      of staging for lung cancer. The purpose of this study was to determine the
      prognostic value of the new UICC staging (1997) among patients with inoperable
      non-small-cell lung cancer (NSCLC) treated with radiotherapy. The status of a
      total of 1354 inoperable patients postintrathoracic irradiation for NSCLC was
      retrospectively analyzed. Restaging was performed according to the staging system
      of the UICC 1997. The median survival (MS) among patients with stage I disease
      was 12.4 months. In the case of stage IA disease, the MS was 17.6 months, which
      was significantly better compared to the 11.2 months observed among patients with
      stage IB disease (P = 0.002). The MS among patients with clinical T2 N1 M0
      disease (stage IIB) was 8.0 months. The MS among those with clinical T3 N0 M0
      disease (stage IIB) was 8.6 months, which was not statistically different from
      the group of patients with stage IIIA disease, who had an MS of 7.6 months. The
      MS among patients with stage IIIB disease was 6.5 months, and among patients with
      stage IV disease, MS was 4.0 months. It was concluded that in patients with
      inoperable NSCLC treated with radiotherapy, the distinction between stages IA and
      IB disease in the new staging system is clinically relevant. There was no
      significant difference in survival between patients with stage IIB and IIIA
      disease. The results clearly show that the prognostic significance of a staging
      system mainly based on surgically treated patients should be analyzed separately
      before it can be used among patients treated with nonsurgical modalities.

PMID- 14656388
TI  - Photodynamic therapy for patients with advanced non-small-cell carcinoma of the
      lung.
AB  - Patients with advanced non-small-cell lung carcinoma (NSCLC) have poor prognoses
      and experience negative sequelae of disease. Patients often suffer from dyspnea
      and/or hemoptysis, with overall pulmonary compromise. Patients with advanced,
      inoperable disease have limited options for treatment. This study summarizes our
      early experience and findings using photodynamic therapy (PDT) as an effective
      modality in the palliation of hemoptysis, dyspnea, and physical airway
      obstruction in cases of inoperable lung cancer. A retrospective review was
      conducted for the first 10 patients diagnosed with stage III/IV obstructive NSCLC
      who underwent PDT at our institution. Endobronchial lesions were identified by
      bronchoscopy. Treatments were initiated 48 hours after intravenous injection of 2
      mg/kg of the photosensitizing agent porfimer sodium (Photofrin, QLT
      PhotoTherapeutics, Vancouver, BC). The porfimer sodium was then activated by
      illumination with a 630 nm wavelength light using a Coherent argon ion laser
      through a flexible bronchoscope. Repeated bronchoscopies were performed 1-3 days
      following initial PDT for evaluation and airway debridement. In 8 cases, a second
      treatment of PDT was administered within 72 hours of the first injection. One
      patient received a third treatment several months later. Three patients also
      received endobronchial stents after PDT. Overall, all 10 patients responded to
      PDT. Physical airway obstruction was reduced in all patients, with a noted
      improvement in bronchoscopic luminal diameter. Acute hemoptysis resolved in all 7
      symptomatic patients. Median survival was 5.5 months post-PDT, while median
      survival postdiagnosis was 10.5 months. Three patients are alive at the time of
      this review at 5-21 months following therapy. Patients with unresectable late
      stage NSCLC have few options for treatment. Our early experience with PDT
      indicates effective relief of hemoptysis, dyspnea, and airway obstruction and
      improves their quality of life.

PMID- 14656390
TI  - Phase II study of sequential treatment of advanced non-small-cell lung cancer:
      three cycles of high-dose epirubicin plus cisplatin followed by weekly
      vinorelbine.
AB  - Previous phase I, II, and III studies on high-dose epirubicin (HDEPI), alone or
      in combination with cisplatin (CP), indicate an interesting activity of this drug
      in the treatment of non-small-cell lung cancer (NSCLC). However, the
      toxicological profile of HDEPI limits its prolonged use. In our experience,
      vinorelbine (VNR) seems to be a suitable drug for long-term monotherapy for
      advanced NSCLC. On these grounds, advanced NSCLC patients were treated with the
      following strategy: 3 consecutive cycles of CP 60 mg/m2 and HDEPI 120 mg/m2 on
      day 1, every 3 weeks; then, irrespective of response, weekly VNR at a dose of 25
      mg/m2 was administered at home. From December 1996 to March 1998, 25 patients
      entered the study. After receiving 3 cycles of CP/HDEPI, 8 patients (32%) had a
      partial response and 3 (12%) had a minor response. Nine patients had stable
      disease (36%) and 4 (16%) had progressive disease. Twenty-three patients received
      weekly VNR, and the median number of administrations was 10 (range, 1-38). After
      VNR treatment, we observed a partial response in 2 patients who previously had
      stable disease. Therefore, the overall response rate to sequential treatment was
      40%; median time to progression was 7 months (range, 2-26 months). The major
      toxicities due to the CP/HDEPI regimen were neutropenia (72%) and alopecia (80%).
      During the VNR treatment, grade 3/4 neutropenia was seen in 36% of patients. The
      doses and the timing of VNR administrations were modified according to toxicity.
      Symptoms such as cough, dyspnea, and pain, present in 21 patients before the
      treatment, improved in 11 cases (52%). Median overall survival is 9 months
      (range, 3-40+ months); one patient is still alive after 40 months. One- and 2
      year survival rates are, respectively, 44% and 16%. This study confirms the
      activity of CP/HDEPI in NSCLC and indicates that the sequential treatment of
      CP/HDEPI for 3 cycles followed by weekly VNR could be considered an effective
      strategy for locally advanced or metastatic NSCLC.

PMID- 14656392
TI  - Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific
      immunotherapy in stage IIIB/IV non-small-cell lung cancer.
AB  - Active specific immunotherapy with liposomal vaccines targeted to the mucinous
      carcinoma-associated glycoprotein MUC1 have shown promising results in animal
      models. The aim of this phase I study was to evaluate the safety and
      immunogenicity of 2 dose levels of the MUC1 liposomal vaccine preparation BLP25.
      Patients with stage IIIB or IV non-small-cell lung cancer received either 20
      microg or 200 microg of the liposomal BLP25 vaccine preparation. Injections were
      administered subcutaneously at weeks 0, 2, 5, and 9. Immunological responses to
      vaccination were measured by antibody production, cytotoxic T lymphocytes (CTL),
      and proliferative T-helper cells. Seventeen patients were entered on study; 12
      patients completed the vaccination protocol. Two patients, 1 in each dose group,
      developed clinically insignificant grade 3 lymphopenia during the study.
      Nonhematologic toxicities were mild and self-limiting, and there were no
      significant long-term injection site reactions. Immunological assays revealed the
      generation of CTLs against MUC1-positive tumor cell lines in 5 of 12 evaluable
      patients. These patients did not have CTLs prior to receiving the vaccine. No
      significant humoral response to the vaccination was observed. No objective
      antitumor responses were observed. Of the 12 patients completing all the
      vaccinations, 4 had stable disease. Median survival time was 5.4 months in the 20
      microg group and 14.6 months in the 200 microg group. In summary, the BLP25
      liposomal vaccine was well tolerated and elicited a primarily cellular immune
      response in these lung cancer patients. This study forms the basis for further
      clinical exploration of the MUC1 liposomal vaccine, BLP25.

PMID- 14656394
TI  - Clinical utility of PET-FDG imaging in differentiation of benign from malignant
      adrenal masses in lung cancer.
AB  - This study was designed to evaluate the sensitivity, specificity, and predictive
      accuracy of PET-FDG imaging in detecting metastatic disease involvement of
      adrenal glands in patients with lung cancer. We wanted to compare efficacy of
      positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging to computed
      tomography (CT) scanning in differentiating benign from malignant involvement of
      adrenal glands in patients with lung cancer. Thirty patients with biopsy-proven
      lung cancer and abnormal findings on PET and/or CT scanning were studied for
      presence of adrenal abnormality suggestive of metastatic disease involvement (n =
      26) or benign adrenal enlargement (n = 4). The results of PET and CT scanning
      were compared to histological findings and/or clinical follow-up for at least 1
      year for presence or absence of adrenal metastases. PET-FDG imaging correctly
      detected the presence of metastatic involvement in 17 of 18 patients and excluded
      metastatic involvement in 11 of 12 patients for sensitivity, specificity, and
      accuracy of 94.4%, 91.6%, and 93.3%, respectively. CT scanning showed enlarged
      adrenals without metastases in 8 of 30 patients and normal-sized adrenals in the
      presence of metastases in 5 of 30 patients. There was a false-positive PET
      finding in 1 patient and a false-negative PET finding in another patient. PET-FDG
      imaging is a highly sensitive, specific, and accurate test to differentiate
      benign from malignant involvement of adrenal glands in patients with lung cancer
      and often ambiguous findings on CT scanning.

PMID- 14656395
TI  - Intraluminal brachytherapy for malignant endobronchial tumors: an update on low
      dose rate versus high-dose rate radiation therapy.
AB  - Although the evolution from low-dose rate (LDR) to high-dose rate (HDR)
      brachytherapy for malignant endobronchial tumors was presumably based on economy,
      patient convenience, and radiation protection, our experience with both
      modalities permits assessment of the pros and cons of each technique. In November
      1991, our HDR remote afterloading brachytherapy unit became operational. By that
      time, we had treated 110 patients (group 1) with malignant endobronchial
      obstruction with LDR brachytherapy. Since then, all patients have been treated
      with HDR brachytherapy. The outcome of our first 110 patients (group 2) treated
      with HDR brachytherapy is presented in this communication, using group 1 as the
      historic control group. In group 1, patients were treated with 1 or 2 sessions of
      30-60 Gy, each calculated at a 1-cm radius. In group 2, patients received 3 or 4
      weekly treatments of 7 Gy, each calculated at a 1-cm radius. The majority of
      patients in each group had previously received a full course of external beam
      irradiation, and a history of laser bronchoscopy was also similar for the 2
      groups. Differences in bronchoscopic response rate (82% vs. 96%, respectively)
      and complications (3.6% vs. 2.7%, respectively) were statistically insignificant
      between the LDR group and the HDR group. We believe HDR brachytherapy is the
      state-of-the-art modality in intraluminal therapy for endobronchial malignancies.

PMID- 14656397
TI  - Procreative liberty: the case for preconception sex selection.
AB  - Preconception sex selection for non-medical reasons raises serious moral, legal
      and social issues. The main concerns include the threat of a sex ratio distortion
      due to a common preference for boys over girls, the charge of sexism, the danger
      of reinforcing gender stereotypical behaviour in sex selected children, and the
      fear of a slippery slope towards creating designer babies. This paper endeavours
      to show that none of the objections to preconception sex selection is conclusive
      and that there is no justification for denying parents the right to choose the
      sex of their prospective children.

PMID- 14656398
TI  - The role of food supplements in the treatment of the infertile man.
AB  - Recently, concerns have been raised about the presumptive increased risk of
      serious undesirable side effects in children born after IVF and intracytoplasmic
      sperm injection (ICSI). These treatments must, therefore, be reserved as the
      ultimate option after evidence-based and cause-directed treatment of the male
      patient with deficient semen has been exhausted. The present authors found that
      sperm quality and function improved with the intake of complementary food
      supplementation using a combination of zinc and folic acid, or the antioxidant
      astaxanthin (Astacarox), or an energy-providing combination containing (actyl)
      carnitine (Proxeed). Also, double blind trials showed that the latter two
      substances increase spontaneous or intrauterine insemination- (IUI-) assisted
      conception rates. Extracts of Pinus maritima bark (Pycnogenol), which inhibits
      the cyclo-oxygenase enzyme, reducing prostaglandin production and inflammatory
      reaction, and extracts of the Peruvian plant Lepidium meyenii were shown to
      improve sperm morphology and concentration, respectively, in uncontrolled trials.
      Linseed (flaxseed) oil contains alfa-linolenic acid and lignans. The former
      corrects the deficient intake of omega-3 essential fatty acids, which is
      correlated with impaired sperm motility among subfertile men. Lignans are
      precursors of enterolacton, which inhibits aromatase and reduces the ratio of 16
      OH over 2-OH oestrogen metabolites. The resulting reduction in oestrogen load may
      favourably influence Sertoli cell function.

PMID- 14656400
TI  - Toward pre-conceptual genetic analysis of human spermatozoa.
AB  - Nuclei of mature mammalian spermatozoa are extraordinarily resistant to chemical
      and thermal injury. Additionally, decondensation of spermatozoa DNA can be
      accompanied by little or no visual changes of the sperm head. This study tested
      whether human spermatozoa could be recovered following several cycles of primer
      extension preamplification (PEP) and used to achieve fertilization and subsequent
      development of human oocytes. An attempt was also made to amplify PEP buffer
      after spermatozoon removal. The results demonstrate that the sperm head can be
      successfully recovered following treatment with KOH or proteinase K followed by
      one to four cycles of PEP. It is also shown that following this treatment, the
      spermatozoa can be injected into the oocytes and will transform into a pronucleus
      if the oocyte is activated by sperm cytosolic fraction. In some cases, it was
      also possible to obtain polymerase chain reaction signals using a buffer after
      sperm cells were removed following several cycles of PEP. Although sperm
      participation in development was confirmed by fluorescence in-situ hybridization,
      light microscopy revealed some degree of damage to spermatozoal chromosomes. It
      is concluded that pre-conceptual analysis of sperm cells may be possible, but
      more research is necessary to determine the optimal conditions that would
      preserve sperm DNA integrity while allowing accurate diagnoses.

PMID- 14656401
TI  - Lack of LGR8 gene mutation in Finnish patients with a family history of
      cryptorchidism.
AB  - Cryptorchidism is the most frequent congenital anomaly of the urogenital tract in
      the male. Although in Western countries 1-2% of males at the age of 3 months are
      diagnosed with this condition, its aetiology is still unknown. Animal models
      suggest a possible genetic basis for this disorder. Recently, the INSL3 (Leydig
      insulin-like peptide) gene and its cognate receptor, LGR8, were found to be
      important in testicular descent by regulating gubernacular development. Male mice
      null for either INSL3 or LGR8 genes exhibited bilateral cryptorchidism. Because
      earlier studies indicated that mutation of the INSL3 gene is not associated with
      the development of human cryptorchidism, this study analysed whether mutations in
      the LGR8 gene could be associated with this disorder. Sequencing of 18 exons of
      the LGR8 gene in 23 cryptorchid Finnish patients and a group of 33 control
      subjects allowed the identification of three nucleotide changes in exons 12 and
      17, showing single base substitutions from A to G at positions 957, 993, and 1810
      of LGR8. Among the three changes, only the 1810 A to G substitution is associated
      with an amino acid change from isoleucine to valine (Ile604Val) located in the
      fifth transmembrane domain of this seven-transmembrane receptor. This change was
      more frequent in a control group of normal fertile adult males and infant boys
      than in the group of cryptorchid males. The change is not associated with altered
      receptor signalling, thus suggesting the presence of a polymorphism unrelated to
      the cryptorchid phenotype. These data indicate that mutations involving the human
      LGR8 gene do not represent a frequent cause of cryptorchidism in the Finnish
      population.

PMID- 14656403
TI  - Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear
      remodelling during spermatogenesis.
AB  - The mechanisms responsible for producing abnormal spermatozoa in the ejaculate
      are relatively unknown. Numerous studies have now shown the presence of nuclear
      DNA strand breaks in human ejaculated spermatozoa and the abnormal persistence of
      apoptotic marker proteins. The reason why human spermatozoa, in particular from
      men with abnormal semen parameters, possess these abnormalities is still not
      clear. Two processes that have been linked to the presence of nuclear DNA strand
      breaks in spermatozoa are anomalies in apoptosis during spermatogenesis or
      problems in the replacement of histones with protamines during spermiogenesis.
      Understanding the mechanisms responsible for producing abnormal spermatozoa in
      the human will improve knowledge about certain causes of male infertility.

PMID- 14656402
TI  - Gene-specific chromatin damage in human spermatozoa can be blocked by
      antioxidants that target mitochondria.
AB  - Incubation of gradient purified human spermatozoa, which are routinely maintained
      in media prior to IVF and intracytoplasmic sperm injection (ICSI), induced DNA
      strand breaks (up to 89 nicks x 10(-3) bp) and chromatin release. Unlike highly
      dispersed Alu repeat sequences, the centromeric heterochromatin was much less
      susceptible to endonuclease attack. In addition to chromatin release, the
      permeability of the sperm membrane was altered as evidenced by reduced
      accessibility of sperm nuclei to decondensation factors in mouse embryo extracts.
      Hybridization of cDNA microarrays with DNA released from spermatozoa revealed a
      consistent hypersensitivity of certain genes to endogenous cleavage including
      TP53, VHL (tumour suppressors), BRCA1 (breast cancer), NOS1 (neurotransmitter),
      PECAM1, FLT1 (angiogenesis) and CDKN1C (cell cycle/imprinted). N-tert-butyl
      hydroxylamine (NTBH), a derivative of the anti-teratogenic alpha-phenyl-N-t-butyl
      nitrone (PBN) and synthetic superoxide dismutase (SOD)/catalase mimetics
      inhibited chromatin release and sustained or dissipated relative mitochondrial
      membrane potential. Together, these results show a link between the
      hyperactivation of sperm mitochondria and chromosomal damage of specific genes in
      vitro, and that the potential risk of disruption of paternally contributed genes
      can be circumvented by antioxidants which are known to target mitochondria.

PMID- 14656405
TI  - Pathophysiology of oligoasthenoteratozoospermia: are we improving in the
      diagnosis?
AB  - Male infertility is one of the most common identifiable causes of human
      reproductive failure. Although considerable progress has been made toward
      understanding sperm physiology and the biology of gamete interaction, still more
      work is needed to achieve objectivity and standardization of some of the
      andrological diagnostic methods used in the clinical setting. More information is
      needed to definitively establish which tests are more accurate predictors of
      sperm performance and how they correlate with pregnancy potential following in
      vivo and in-vitro interventions. Infertile men can be successfully treated with
      defined urological and medical therapies or with assisted reproductive
      technologies. Among the latter, intracytoplasmic sperm injection (ICSI) has
      become a validated means to overcome multiple sperm deficiencies. However, male
      infertility remains idiopathic in a large proportion of cases. As a consequence,
      it is expected that simplified and more cost-efficient therapeutic modalities
      will be developed as additional basic (cellular-molecular) and
      pathophysiological/clinical knowledge is gained.

PMID- 14656406
TI  - Sequence of ejaculation affects the spermatozoon as a carrier and its message.
AB  - It is a widespread misunderstanding that the human ejaculation produces a
      homogeneous fluid with constant environment for the spermatozoa. On the contrary,
      spermatozoa are mainly expelled together with the zinc-rich prostatic fluid in
      the first ejaculation fractions. In nature, these spermatozoa most likely enter
      the cervical mucus before any significant contact with the later, sperm hostile
      fractions takes place. Spermatozoa collected in the laboratory for diagnosis,
      treatment or research purposes face challenges in the form of light, high oxygen
      concentration, low carbon dioxide concentration, increased pH, extreme variations
      in osmolarity, and changed bioavailability of zinc and calcium in the man-made
      laboratory product called seminal plasma. Possible future implications of these
      unphysiological conditions are discussed in relation to assisted reproduction and
      sperm research.

PMID- 14656407
TI  - Effects of cryopreservation on testicular sperm nuclear DNA fragmentation and its
      relationship with assisted conception outcome following ICSI with testicular
      spermatozoa.
AB  - The objective of the study was to investigate the effects of freeze-thawing on
      testicular sperm DNA fragmentation, fertilization rates and pregnancy rates
      following intracytoplasmic sperm injection with testicular spermatozoa (TESE).
      This ongoing prospective study included 88 couples attending for infertility
      treatment where the man presented with obstructive azoospermia at the Regional
      Fertility Centre, Belfast, UK. Patients were allocated to receive TESE treatment
      with fresh or freeze-thawed spermatozoa. Sperm aliquots were stored in liquid
      nitrogen at -196 degrees C following static phase vapour cooling or cooling at
      controlled rates using a programmable freezer. Samples were thawed at either room
      temperature or 37 degrees C. Sperm nuclear DNA; assessed by the alkaline Comet
      assay, was significantly damaged by slow freezing followed by fast thawing.
      Pregnancies were more likely to be achieved with spermatozoa displaying markedly
      less DNA damage. However, no differences were observed in the fertilization
      rates, the number of blastomeres or the cumulative embryo score between TESE
      cycles using either fresh or frozen thawed testicular spermatozoa. The pregnancy
      rates tended to be higher following fresh TESE cycles (30%) compared with TESE
      cycles using frozen-thawed testicular spermatozoa (26%), although this difference
      did not reach statistical significance. It is concluded that cryopreservation of
      testicular spermatozoa may reduce pregnancy rates, although this will only be
      confirmed by a much larger multi-centre trial.

PMID- 14656408
TI  - Novel PDE5 inhibitors for the treatment of male erectile dysfunction.
AB  - Erectile dysfunction (ED) affects the lives of approximately 150 million men
      worldwide. ED may be a cause of male sub-fertility in a significant proportion of
      patients. There is now an expanding armamentarium for the management of ED,
      including oral agents such as phosphodiesterase type 5 (PDE5) inhibitors. PDE5
      inhibitors may also be useful in situations of temporary ED in couples undergoing
      IVF. Two novel PDE5 inhibitors have been commercially launched in the European
      Union in the first quarter of 2003. This article reviews the pharmacology and
      clinical efficacy of these new agents and their potential role in treating
      patients with male sub-fertility.

PMID- 14656409
TI  - Biochemical markers of sperm function: male fertility and sperm selection for
      ICSI.
AB  - The expression of a 70 kDa chaperone protein, HspA2 (formerly called CK-M), has
      been identified in mature human spermatozoa. The central role of HspA2 has been
      established, as the expression level of this protein is related to sperm cellular
      maturity, DNA integrity, chromatin maturity, chromosomal aneuploidy frequency and
      sperm function, including fertilizing potential. The spermiogenetic events of
      cytoplasmic extrusion and remodelling of the plasma membrane, which facilitate
      the formation of zona pellucida binding site(s) in human spermatozoa, are
      related. Finally, the presence of the hyaluronic acid (HA) receptor on the plasma
      membrane of mature sperm coupled with the HA-coated slide sperm-binding assay,
      facilitates the testing of infertile men and the selection of single mature
      spermatozoa for ICSI. Because mature spermatozoa have no residual cytoplasm, the
      HA-bound sperm fraction is also enriched in spermatozoa that are normal by the
      Kruger strict morphology method.

PMID- 14656410
TI  - Presence and significance of somatic cell apoptosis markers in human ejaculated
      spermatozoa.
AB  - Ejaculated spermatozoa, particularly in infertile men, have been shown to display
      morphological and biochemical features that are typical of an apoptotic phenotype
      in somatic cells. Deregulation of apoptosis is known to play roles in a number of
      disease processes, but roles for apoptosis in ejaculated spermatozoa and male
      infertility are poorly defined or have not been studied. Preliminary data
      demonstrated that populations of ejaculated spermatozoa express: (i) various
      degrees of plasma membrane translocation of phosphatidylserine and DNA
      fragmentation; and (ii) active caspase-3, the main executor of apoptosis in
      somatic cells, with an apparent exclusive cellular location to the mid-piece.
      Tests are currently being carried out on the effects of well-known apoptosis
      agonists and caspase inhibitors on such markers using purified populations of
      leukocyte-free ejaculated human spermatozoa. The main objective is to determine
      if somatic cell apoptosis markers are relevant indicators and/or causative
      factors of male infertility.

PMID- 14656411
TI  - DNA fragmentation of spermatozoa and assisted reproduction technology.
AB  - Despite the ever-increasing knowledge of the fertilization process, there is
      still a need for better understanding of the causes of sperm DNA fragmentation
      and its impact on fertilization and pregnancy. For this reason, human sperm DNA
      fragmentation was investigated by means of the terminal deoxynucleotidyl
      transferase-mediated dUDP nick-end labelling (TUNEL) assay and the production of
      reactive oxygen species (ROS) in the ejaculate and in the spermatozoa themselves.
      These data were correlated with fertilization and pregnancy data from IVF and
      intracytoplasmic sperm injection (ICSI) patients. Sperm DNA fragmentation did not
      correlate with fertilization rate, but there was a significantly reduced
      pregnancy rate in IVF patients inseminated with TUNEL-positive spermatozoa. ICSI
      patients exhibited the same tendency. This implies that spermatozoa with damaged
      DNA are able to fertilize an oocyte, but at the time the paternal genome is
      switched on, further development stops. The determination of ROS in the ejaculate
      and the percentage of ROS-producing spermatozoa revealed markedly stronger
      correlations between sperm functions (i.e. motility) and the percentage of ROS
      producing spermatozoa. The influence of seminal leukocytes, known to produce
      large amounts of oxidants, on sperm DNA fragmentation should not be neglected.

PMID- 14656412
TI  - Semen quality and intrauterine insemination.
AB  - There is good evidence in literature that intrauterine insemination (IUI) is the
      best first line treatment and most cost-effective procedure for moderate male
      factor subfertility. It seems very difficult to identify individual semen
      parameters predicting the likelihood of pregnancy after IUI. This can be
      explained by a lack of standardization of semen analysis, but many other
      methodological variables may also influence IUI success rates such as the patient
      selection, type of ovarian stimulation and number of inseminations per cycle. A
      review of the literature confirmed that sperm morphology using strict criteria
      and the inseminating motile sperm count (IMC) after sperm preparation are the two
      most important sperm parameters to assess the real impact of semen quality on IUI
      outcome. A universal threshold level above which IUI can be performed with
      acceptable pregnancy rates has not been determined yet, although IUI success
      seems to be impaired with <5% normal spermatozoa and an IMC of <1 x 10(6). Until
      now, no method of sperm preparation has been shown to be superior with regard to
      pregnancy rate after IUI. Whether supplementation of culture media with
      substances such as antioxidants and platelet activating factor may improve the
      results remains the subject of further research.

PMID- 14656414
TI  - Nocardiosis: a review.
AB  - Infections caused by Nocardia species are infrequent but challenging to
      clinicians. They cause a wide variety of diseases in both normal and
      immunocompromised patients. In recent years, the number of case reports has been
      increasing, and this can be attributed to the improvements in diagnostic
      capabilities and the higher clinical index of suspicion accompanying the
      increased prevalence of immunosuppressed patients. The treatment of nocardiosis
      also requires expertise. This report reviews the epidemiology, physiopathology,
      clinical manifestations, diagnosis and treatment of this aerobic bacterial
      disease.

PMID- 14656415
TI  - Electron microscopy and the investigation of new infectious diseases.
AB  - OBJECTIVES: To review and assess the role of electron microscopy in the
      investigation of new infectious diseases. DESIGN: To design a screening strategy
      to maximize the likelihood of detecting new or emerging pathogens in clinical
      samples. RESULTS: Electron microscopy remains a useful method of investigating
      some viral infections (infantile gastroenteritis, virus-induced outbreaks of
      gastroenteritis and skin lesions) using the negative staining technique. In
      addition, it remains an essential technique for the investigation of new and
      emerging parasitic protozoan infections in the immunocompromised patients from
      resin-embedded tissue biopsies. Electron microscopy can also have a useful role
      in the investigation of certain bacterial infections. CONCLUSIONS: Electron
      microscopy still has much to contribute to the investigation of new and emerging
      pathogens, and should be perceived as capable of producing different, but equally
      relevant, information compared to other investigative techniques. It is the
      application of a combined investigative approach using several different
      techniques that will further our understanding of new infectious diseases.

PMID- 14656416
TI  - Emergence of community-acquired methicillin-resistant Staphylococcus aureus
      (MRSA) infection in Queensland, Australia.
AB  - OBJECTIVES: To investigate the incidence and epidemiology of non-multiresistant
      methicillin-resistant Staphylococcus aureus (nmMRSA) infection in south-east
      Queensland, Australia. STUDY DESIGN: A retrospective survey was done of hospital
      records of all patients who had non-multiresistant MRSA isolated at Ipswich
      Hospital (a 250-bed general hospital, 40 km south-west of Brisbane, Queensland,
      Australia) between March 2000 and June 2001. Laboratory typing of these isolates
      was done with antibiogram, pulsed-field gel electrophoresis, bacteriophage typing
      and coagulase gene typing. RESULTS: There were 44 infections caused by nmMRSA.
      Seventeen infections (39%) occurred in patients from the south-west Pacific
      Islands (predominantly Samoa, Tonga and New Zealand). Laboratory typing showed
      that the isolates in Pacific Islanders were Pacific Island strains, and 16/17 of
      these infections were community acquired. Twenty-three infections (52%) occurred
      in Caucasians. Eleven of the isolates from Caucasians (48%) were a new
      predominantly community-acquired strain that we have termed the 'R' pulsotype,
      nine (39%) were Pacific Island strains, and three (13%) were health care
      institution-associated strains. Four infections occurred in patients who were not
      Caucasians or Pacific Islanders. Overall, 34 of all 44 infections (77%) were
      community acquired. CONCLUSIONS: Non-multiresistant MRSA infection, relatively
      frequently observed in Pacific Islanders in south-east Queensland, is now a risk
      for Caucasians as well, and is usually community acquired. Clinicians should
      consider taking microbiological specimens for culture and antimicrobial
      susceptibility testing in patients with suspected staphylococcal infections who
      are not responding to empirical therapy with beta-lactam antibiotics.

PMID- 14656417
TI  - Tuberculosis infection notification in Swiss medical students during their
      clinical electives.
AB  - OBJECTIVE: The aim of this study was to assess the tuberculin skin test
      conversion incidence in Swiss medical students. METHODS: This was a prospective
      cohort study of medical students at the University of Zurich, using a
      standardized tuberculin skin test before and after clinical electives. RESULTS:
      Two hundred and sixty-two students accepted the invitation to the pre-clerkship
      test, and 155 (59.2%) subjects were retested after an average period of 2.25
      years. An increase of more than 10 mm in the transverse diameter of the
      induration in the retest compared to the baseline test was observed in 12 (7.7%)
      students. The annual conversion rate was 3.4% (95% CI 1.8-6.0%). CONCLUSIONS:
      Even in an industrialized country, the risk of tuberculosis infection--as
      estimated by the tuberculin skin test--is substantial for health care
      professionals. Possible explanations for the high incidence and possible bias are
      discussed.

PMID- 14656418
TI  - How reliable is the history of chickenpox? Varicella serology among children up
      to 14 years of age.
AB  - OBJECTIVES: The aim of this study was to assess the seroprevalence of antibodies
      to varicella-zoster virus (VZV) in children of northern Greece and to estimate
      the reliability of varicella history. METHODS: A serosurvey of 632 children, aged
      13 months to 14 years (median 5.2 years), was conducted between April 1999 and
      July 2001. Serum samples were tested by enzyme-linked immunosorbent assay (ELISA)
      for IgG antibodies to VZV (IgG Genzyme Virotech GmbH). A history of varicella in
      these children was obtained from the parents of all these patients. Also, a check
      of state health cards of the patients was done. RESULTS: Two hundred and forty
      eight (39%) of the children were seropositive for VZV. Two hundred and thirty
      (36%) of the 632 children claimed to have had previous varicella infection; 87.8%
      were seropositive, and 12.2% lacked antibodies to VZV. One hundred and seven of
      the 230 children with a history of varicella had the information about the
      disease confirmed, as it was reported on their state health card by a
      pediatrician; 10.2% were seronegative for VZV. Absence of history of varicella
      was reported in 402 (63.6%) of the 632 children; 88.6% of those were
      seronegative, and 11.4% were seropositive. The percentage of incorrect negative
      history ranged from 6% (13-60 months of age) to 48% (120-168 months of age).
      CONCLUSIONS: A large proportion of the study group (61%), mainly below 7 years of
      age, is susceptible to varicella. The positive predictive value of a history of
      varicella is 87.8%, whereas the negative predictive value of a negative history
      is 11.4%, which means that there is an 88.6% probability of a negative history
      being correct. Varicella serology may be reasonable prior to vaccination in
      children >10 years old with a negative chickenpox history. However, if one
      excludes cost considerations, it is also reasonable to vaccinate all children,
      irrespective of serostatus.

PMID- 14656419
TI  - Ganciclovir therapy in cytomegalovirus (CMV) infection in immunocompetent
      pediatric patients.
AB  - OBJECTIVES: To evaluate the outcome of immunocompetent pediatric patients who had
      positive cytomegalovirus (CMV) antigenemia and received ganciclovir. METHODS: A
      retrospective review was done of patients who had a CMV infection based on
      positive antigenemia. Medical charts were reviewed for the following information:
      age, sex, underlying disease, symptoms and signs, laboratory results,
      complementary diagnostic procedures, duration and dose of ganciclovir therapy,
      concomitant medications, complications, and outcome. RESULTS: Sixty-four patients
      with positive CMV antigenemia were identified; 15 patients were excluded from the
      study because of their underlying diseases. Of the remaining 49 patients, 26
      (53%) were female; the median age was 11.5 months (range 0.3-132 months). Sixty
      one percent (30/49) of these patients received ganciclovir (5-10 mg/kg/day) for a
      median of 14 days (range 7-42 days). Clinical findings included: fever, anemia,
      hepatomegaly, failure to thrive, elevated liver enzymes, splenomegaly, seizures,
      and thrombocytopenia. Sixty-three percent (19/30) of the treated patients had
      negative antigenemia at the end of therapy. CMV antigenemia remained positive in
      six (20%) patients. Nine patients received a second course of ganciclovir.
      CONCLUSIONS: Ganciclovir was effective in 80% of patients, as determined by
      negative antigenemia at the end of therapy.

PMID- 14656420
TI  - Phaeohyphomycosis of the central nervous system in immunocompetent hosts: report
      of a case and review of the literature.
AB  - BACKGROUND: Phaeohyphomycosis refers to infections caused by phaeoid fungi that
      can have an aggressive course in normal hosts. Involvement of the central nervous
      system may occur with a generally poor outcome. Clinical report and literature
      review: We report a case of Bipolaris sp. brain abscess in an immunologically
      competent host. We also review all previous cases of cerebral phaeohyphomycosis
      in normal hosts reported in the literature to date. CONCLUSIONS: Central nervous
      system phaeohyphomycosis remains an unusual disease; however, its incidence has
      been increasing in recent years. The prognosis of this condition is still poor,
      despite medical and surgical interventions. Aggressive diagnostic approaches and
      careful interpretation of cultures might modify the natural history of this
      disease.

PMID- 14656421
TI  - Efficacy of vancomycin plus levofloxacin combination therapy for refractory
      pericarditis due to multiresistant Streptococcus pneumoniae.

PMID- 14656422
TI  - Emergence of high-level fluoroquinolone-resistant Streptococcus pneumoniae in
      Turkey.

PMID- 14656423
TI  - Brucella abortus epididymo-orchitis relapsing in the opposite testis 3 months
      after antibiotic therapy and development of aspermia.

PMID- 14656424
TI  - Dogs as possible mechanical carriers of Toxoplasma, and their fur as a source of
      infection of young children.

PMID- 14656427
TI  - His-Asp signal transduction via a monomeric histidine phosphotransfer protein.

PMID- 14656428
TI  - A branch point in chorismate synthase research.

PMID- 14656429
TI  - Swivels and stators in the Hsp40-Hsp70 chaperone machine.

PMID- 14656430
TI  - A new era in membrane channel biology.

PMID- 14656431
TI  - Electrical power fuels rotary ATP synthase.
AB  - ATP synthesis by F-type ATP synthases consumes energy stored in a transmembrane
      electrochemical gradient of protons or sodium ions. The electric component of the
      ion motive force is crucial for ATP synthesis. Here, we incorporate recent
      results on structure and function of the F(0) domain and present a mechanism for
      torque generation with the fundamental nature of the membrane potential as
      driving force in the core.

PMID- 14656432
TI  - The crystal structure of the yeast Hsp40 Ydj1 complexed with its peptide
      substrate.
AB  - The mechanisms by which Hsp40 functions as a molecular chaperone to recognize and
      bind non-native polypeptides is not understood. We have identified a peptide
      substrate for Ydj1, a member of the type I Hsp40 from yeast. The structure of the
      Ydj1 peptide binding fragment and its peptide substrate complex was determined to
      2.7 A resolution. The complex structure reveals that Ydj1 peptide binding
      fragment forms an L-shaped molecule constituted by three domains. The domain I
      exhibits a similar protein folds as domain III while the domain II contains two
      Zinc finger motifs. The peptide substrate binds Ydj1 by forming an extra beta
      strand with domain I of Ydj1. The Leucine residue in the middle of the peptide
      substrate GWLYEIS inserts its side chain into a hydrophobic pocket formed on the
      molecular surface of Ydj1 domain I. The Zinc finger motifs located in the Ydj1
      domain II are not in the vicinity of peptide substrate binding site.

PMID- 14656433
TI  - Nucleobase pairing in expanded Watson-Crick-like genetic information systems.
AB  - To guide the design of alternative genetic systems, we measured melting
      temperatures of DNA duplexes containing matched and mismatched nucleobase pairs
      from natural and unnatural structures. The pairs were analyzed in terms of
      structural features, including nucleobase size, number of hydrogen bonds formed,
      the presence of uncompensated hydrogen bonding functional groups, the nature of
      the bond joining the nucleobase to the sugar, and nucleobase charge. The results
      suggest that stability of nucleobase pairs correlates with the number of H-bonds,
      size complementarity, the presence of uncompensated functional groups, and the
      presence of charge on a nucleobase. Each of these properties appear to be more
      significant than the nature of the glycosidic bond and sequence context. The
      results provide guidelines for constructing stable Watson-Crick like nucleobase
      pairs with unnatural nucleobases. The experiments also demonstrate that expanded
      genetic systems can be constructed using size complementary nucleobase pairs that
      contain three hydrogen bonds.

PMID- 14656434
TI  - The structure of chorismate synthase reveals a novel flavin binding site
      fundamental to a unique chemical reaction.
AB  - The crystal structure of chorismate synthase (CS) from Streptococcus pneumoniae
      has been solved to 2.0 A resolution in the presence of flavin mononucleotide
      (FMN) and the substrate 5-enolpyruvyl-3-shikimate phosphate (EPSP). CS catalyses
      the final step of the shikimate pathway and is a potential therapeutic target for
      the rational design of novel antibacterials, antifungals, antiprotozoals, and
      herbicides. CS is a tetramer with the monomer possessing a novel beta-alpha-beta
      fold. The interactions between the enzyme, cofactor, and substrate reveal the
      structural reasons underlying the unique catalytic mechanism and identify the
      amino acids involved. This structure provides the essential initial information
      necessary for the generation of novel anti-infective compounds by a structure
      guided medicinal chemistry approach.

PMID- 14656435
TI  - The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct
      receptor specificity.
AB  - EDA is a tumor necrosis factor family member involved in ectodermal development.
      Splice variants EDA-A1 and EDA-A2 differ only by the presence of Glu 308 and Val
      309 in the expected receptor binding region of EDA-A1 but not EDA-A2. This two
      amino acid difference functions as a switch controlling receptor specificity. EDA
      A1 binds only to EDAR, while EDA-A2 is specific for XEDAR. In order to understand
      the structural basis of this switch, we determined the X-ray crystal structures
      of the TNF domain of both EDA-A1 and EDA-A2 at 2.3 A and 2.2 A, respectively.
      While the backbone conformation around the splice difference is similar in both
      isoforms, the conformation of the following loop, the surface charge, and the
      shape of the expected receptor binding site differ significantly.

PMID- 14656436
TI  - Crystal structure of a micro-like calpain reveals a partially activated
      conformation with low Ca2+ requirement.
AB  - The two Ca2+-dependent cysteine proteases, micro- and m-calpain, are involved in
      various Ca2+-linked signal pathways but differ markedly in their Ca2+
      requirements for activation. We have determined the structure of a micro-like
      calpain, which has 85% micro-calpain sequence (the first 48 and the last 62
      residues of the large subunit are those from m-calpain) and a low Ca2+
      requirement. This construct was used because micro-calpain itself is too poorly
      expressed. The structure of micro-like calpain is very similar in overall fold to
      that of m-calpain as expected, but differs significantly in two aspects. In
      comparison with m-calpain, the catalytic triad residues in micro-like calpain,
      His and Cys, are much closer together in the absence of Ca2+, and significant
      portions of the Ca2+ binding EF-hand motifs are disordered and more flexible.
      These structural differences imply that Ca2+-free micro-calpain may represent a
      partially activated structure, requiring lower Ca2+ concentration to trigger its
      activation.

PMID- 14656437
TI  - Crystal structure of the human myeloid cell activating receptor TREM-1.
AB  - Triggering receptors expressed on myeloid cells (TREM) are a family of recently
      discovered receptors that play important roles in innate immune responses, such
      as to activate inflammatory responses and to contribute to septic shock in
      response to microbial-mediated infections. To date, two TREM receptors in human
      and several homologs in mice have been identified. We report the 2.6 A resolution
      crystal structure of the extracellular domain of human TREM-1. The overall fold
      of the receptor resembles that of a V-type immunoglobulin domain with differences
      primarily located in the N-terminal strand. TREM-1 forms a "head-to-tail" dimer
      with 4100 A(2) interface area that is partially mediated by a domain swapping
      between the first strands. This mode of dimer formation is different from the
      "head-to-head" dimerization that existed in V(H)V(L) domains of antibodies or V
      domains of T cell receptors. As a result, the dimeric TREM-1 most likely contains
      two distinct ligand binding sites.

PMID- 14656438
TI  - Insights into cyclin groove recognition: complex crystal structures and inhibitor
      design through ligand exchange.
AB  - Inhibition of CDK2/CA (cyclin-dependent kinase 2/cyclin A complex) activity
      through blocking of the substrate recognition site in the cyclin A subunit has
      been demonstrated to be an effective method for inducing apoptosis in tumor
      cells. We have used the cyclin binding motif (CBM) present in the tumor
      suppressor proteins p21(WAF1) and p27(KIP1) as a template to optimize the minimal
      sequence necessary for CDK2/CA inhibition. A series of peptides were prepared,
      containing nonnatural amino acids, which possess nano- to micromolar CDK2
      inhibitory activity. Here we present X-ray structures of the protein complex
      CDK2/CA, together with the cyclin groove-bound peptides H-Ala-Ala-Abu-Arg-Ser-Leu
      Ile-(p-F-Phe)-NH(2) (peptide 1), H-Arg-Arg-Leu-Ile-Phe-NH(2) (peptide 2), Ac-Arg
      Arg-Leu-Asn-(m-Cl-Phe)-NH(2) (peptide 3), H-Arg-Arg-Leu-Asn-(p-F-Phe)-NH(2)
      (peptide 4), and H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH(2) (peptide 5). Some of the
      peptide complexes presented here were obtained through the novel technique of
      ligand exchange within protein crystals. This method may find general application
      for obtaining complex structures of proteins with surface-bound ligands.

PMID- 14656439
TI  - Chaperone binding at the ribosomal exit tunnel.
AB  - The exit tunnel region of the ribosome is well established as a focal point for
      interaction between the components that guide the fate of nascent polypeptides.
      One of these, the chaperone trigger factor (TF), associates with the 50S
      ribosomal subunit through its N-terminal domain. Targeting of TF to ribosomes is
      crucial to achieve its remarkable efficiency in protein folding. A similar tight
      coupling to translation is found in signal recognition particle (SRP)-dependent
      protein translocation. Here, we report crystal structures of the E. coli TF
      ribosome binding domain. TF is structurally related to the Hsp33 chaperone but
      has a prominent ribosome anchor located as a tip of the molecule. This tip
      includes the previously established unique TF signature motif. Comparison reveals
      that this feature is not found in SRP structures. We identify a conserved helical
      kink as a hallmark of the TF structure that is most likely critical to ensure
      ribosome association.

PMID- 14656440
TI  - The structure of Escherichia coli RusA endonuclease reveals a new Holliday
      junction DNA binding fold.
AB  - Holliday junction resolution performed by a variety of structure-specific
      endonucleases is a key step in DNA recombination and repair. It is believed that
      all resolvases carry out their reaction chemistries in a similar fashion,
      utilizing a divalent cation to facilitate the hydrolysis of the phosphodiester
      backbone of the DNA, but their architecture varies. To date, with the exception
      of bacteriophage T4 endonuclease VII, each of the known resolvase enzyme
      structures has been categorized into one of two families: the integrases and the
      nucleases. We have now determined the structure of the Escherichia coli RusA
      Holliday junction resolvase, which reveals a fourth structural class for these
      enzymes. The structure suggests that dimer formation is essential for Mg(2+)
      cation binding and hence catalysis and that like the other resolvases, RusA
      distorts its Holliday junction target upon binding. Key residues identified by
      mutagenesis experiments are well positioned to interact with the DNA.

PMID- 14656441
TI  - The yeast YPD1/SLN1 complex: insights into molecular recognition in two-component
      signaling systems.
AB  - In Saccharomyces cerevisiae, a branched multistep phosphorelay signaling pathway
      regulates cellular adaptation to hyperosmotic stress. YPD1 functions as a
      histidine-phosphorylated protein intermediate required for phosphoryl group
      transfer from a membrane-bound sensor histidine kinase (SLN1) to two distinct
      response regulator proteins (SSK1 and SKN7). These four proteins are
      evolutionarily related to the well-characterized "two-component" regulatory
      proteins from bacteria. Although structural information is available for many two
      component signaling proteins, there are very few examples of complexes between
      interacting phosphorelay partners. Here we report the first crystal structure of
      a prototypical monomeric histidine-containing phosphotransfer (HPt) protein YPD1
      in complex with its upstream phosphodonor, the response regulator domain
      associated with SLN1.

PMID- 14656442
TI  - Tandem histone folds in the structure of the N-terminal segment of the ras
      activator Son of Sevenless.
AB  - The Ras activator Son of Sevenless (Sos) contains a Cdc25 homology domain,
      responsible for nucleotide exchange, as well as Dbl/Pleckstrin homology (DH/PH)
      domains. We have determined the crystal structure of the N-terminal segment of
      human Sos1 (residues 1-191) and show that it contains two tandem histone folds.
      While the N-terminal domain is monomeric in solution, its structure is
      surprisingly similar to that of histone dimers, with both subunits of the histone
      "dimer" being part of the same peptide chain. One histone fold corresponds to the
      region of Sos that is clearly similar in sequence to histones (residues 91-191),
      whereas the other is formed by residues in Sos (1-90) that are unrelated in
      sequence to histones. Residues that form a contiguous patch on the surface of the
      histone domain of Sos are conserved from C. elegans to humans, suggesting a
      potential role for this domain in protein-protein interactions.

PMID- 14656443
TI  - Protein kinase A in complex with Rho-kinase inhibitors Y-27632, Fasudil, and H
      1152P: structural basis of selectivity.
AB  - Protein kinases require strict inactivation to prevent spurious cellular
      signaling; overactivity can cause cancer or other diseases and necessitates
      selective inhibition for therapy. Rho-kinase is involved in such processes as
      tumor invasion, cell adhesion, smooth muscle contraction, and formation of focal
      adhesion fibers, as revealed using inhibitor Y-27632. Another Rho-kinase
      inhibitor, HA-1077 or Fasudil, is currently used in the treatment of cerebral
      vasospasm; the related nanomolar inhibitor H-1152P improves on its selectivity
      and potency. We have determined the crystal structures of HA-1077, H-1152P, and Y
      27632 in complexes with protein kinase A (PKA) as a surrogate kinase to analyze
      Rho-kinase inhibitor binding properties. Features conserved between PKA and Rho
      kinase are involved in the key binding interactions, while a combination of
      residues at the ATP binding pocket that are unique to Rho-kinase may explain the
      inhibitors' Rho-kinase selectivity. Further, a second H-1152P binding site
      potentially points toward PKA regulatory domain interaction modulators.

PMID- 14656444
TI  - The first structure of an RNA m5C methyltransferase, Fmu, provides insight into
      catalytic mechanism and specific binding of RNA substrate.
AB  - The crystal structure of E. coli Fmu, determined at 1.65 A resolution for the
      apoenzyme and 2.1 A resolution in complex with AdoMet, is the first
      representative of the 5-methylcytosine RNA methyltransferase family that includes
      the human nucleolar proliferation-associated protein p120. Fmu contains three
      subdomains which share structural homology to DNA m(5)C methyltransferases and
      two RNA binding protein families. In the binary complex, the AdoMet cofactor is
      positioned within the active site near a novel arrangement of two conserved
      cysteines that function in cytosine methylation. The site is surrounded by a
      positively charged cleft large enough to bind its unique target stem loop within
      16S rRNA. Docking of this stem loop RNA into the structure followed by molecular
      mechanics shows that the Fmu structure is consistent with binding to the folded
      RNA substrate.

PMID- 14656445
TI  - Crystal structure of scallop Myosin s1 in the pre-power stroke state to 2.6 a
      resolution: flexibility and function in the head.
AB  - We have extended the X-ray structure determination of the complete scallop myosin
      head in the pre-power stroke state to 2.6 A resolution, allowing an atomic
      comparison of the three major (weak actin binding) states of various myosins. We
      can now account for conformational differences observed in crystal structures in
      the so-called "pliant region" at the motor domain-lever arm junction between
      scallop and vertebrate smooth muscle myosins. A hinge, which may contribute to
      the compliance of the myosin crossbridge, has also been identified for the first
      time within the regulatory light-chain domain of the lever arm. Analysis of
      temperature factors of key joints of the motor domain, especially the SH1 helix,
      provides crystallographic evidence for the existence of the "internally
      uncoupled" state in diverse isoforms. The agreement between structural and
      solution studies reinforces the view that the unwinding of the SH1 helix is a
      part of the cross-bridge cycle in many myosins.

PMID- 14656446
TI  - Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids
      in schizophrenic and bipolar mood disorder patients.
AB  - Oxidative stress-mediated cell damage has been considered in the pathophysiology
      of schizophrenia. Abnormal findings have often been considered related to
      differences in ethnicity, life style, dietary patterns and medications, all of
      which influence indices of oxidative stress and oxidative cell damage. To
      minimize these confounds, schizophrenic patients were compared with age-matched
      control subjects with the same ethnic background and similar lifestyle, as well
      as with bipolar mood disorder (BMD) patients. Levels of antioxidant defense
      enzymes (i.e. superoxide dismutase, SOD; catalase, CAT; and glutathione
      peroxidase, GPx) were lower in schizophrenic patients than in controls,
      indicating conditions for increased oxidative stress. The contents of plasma
      thiobarbituric acid reactive substances (TBARS) were only marginally higher in
      schizophrenic patients, who had normal levels of arachidonic acid (AA), a major
      source of TBARS, indicating no significant oxidative membrane lipid peroxidation.
      Levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), however,
      were significantly lower in schizophrenic patients. When the same indices in BMD
      patients were compared with findings in matched controls, levels of only SOD and
      CAT were lower in the patients, whereas GPx was not. Again, as in schizophrenia,
      the contents of TBARS were marginally higher in BMD patients with no change in
      levels of AA. Levels of alpha-linolenic acid and EPA were significantly lower and
      levels of DHA were slightly lower in BMD patients. These data indicate that
      certain biochemical characteristics may be common to a spectrum of psychiatric
      disorders, and suggest supplementation of antioxidants and essential fatty acids
      might affect clinical outcome.

PMID- 14656447
TI  - Overproduction of neutrophil radical oxygen species correlates with negative
      symptoms in schizophrenic patients: parallel studies on neutrophil chemotaxis,
      superoxide production and bactericidal activity.
AB  - Defective neutrophil function in schizophrenic patients has recently been
      reported. There are several lines of evidence to support the contribution of
      oxygen free radicals in schizophrenia, including increased lipid peroxidation,
      fatty acids and alterations in blood levels of anti-oxidant enzymes. Eighteen
      schizophrenic patients (DSM-IV) and 15 healthy controls were studied. Neutrophil
      chemotaxis, superoxide production and bactericidal activity were investigated. A
      statistically significant increase of superoxide anion release was found in
      schizophrenic patients compared with controls (mean+/-S.E.M., patients: 6.89+/
      0.30 nmol O2-/10(6) cells/min, controls: 5.13+/-0.55 nmol O2-/10(6) cells/min).
      Moreover, a significant positive correlation between superoxide production and
      negative symptoms as assessed by the Positive and Negative Syndrome Scale was
      demonstrated. No differences were detected in chemotaxis and phagocytosis between
      schizophrenic patients and healthy controls. The present findings of a positive
      correlation between superoxide generation and negative symptoms in schizophrenic
      patients support the hypothesis that superoxide anion may participate in the
      pathogenesis of schizophrenia, as an excess of free radicals could contribute to
      the deterioration phase of the disease. Further studies are required to establish
      the role of oxidative stress in the ethiopathogenesis of schizophrenia.

PMID- 14656448
TI  - Memory for trauma-related information in Holocaust survivors with PTSD.
AB  - The impact of trauma-related information on memory performance in aging Holocaust
      survivors with post-traumatic stress disorder (PTSD) was evaluated. Explicit and
      implicit memory for neutral and Holocaust-related words was assessed in Holocaust
      survivors with PTSD (PTSD+, n=31), in Holocaust survivors without PTSD (PTSD-,
      n=17), and in healthy Jewish adults not exposed to the Holocaust (non-exposed,
      n=34) using the paired associates learning and word-stem completion tests,
      respectively. The PTSD+ group had significantly poorer paired associate recall
      than the PTSD- and non-exposed groups, and showed a significantly different
      response to the introduction of Holocaust-related words. The PTSD+ group recalled
      significantly more words from the Holocaust-related than the neutral word pairs,
      whereas word type had little effect on paired associate recall in the other two
      groups. In contrast, there were no group differences in implicit memory
      performance or in the effect of Holocaust-related words on implicit memory. Among
      Holocaust survivors, explicit recall of Holocaust-related word pairs was
      associated with intrusive PTSD symptoms. These results suggest that aging
      Holocaust survivors with PTSD preferentially form new associations with trauma
      related stimuli as compared with neutral stimuli. The presence of such a
      disturbance of associative learning decades after the Holocaust may underlie the
      persistence of psychological symptoms and, in particular, the intrusive symptoms
      of PTSD. This trauma-related facilitation of explicit memory, together with
      generally poorer explicit memory, may help to explain the bi-directional nature
      of the memory impairments in PTSD.

PMID- 14656449
TI  - Long-term immune-endocrine effects of bereavement: relationships with anxiety
      levels and mood.
AB  - Psychological, endocrine and immune parameters were measured over a 6-month
      period in 14 healthy subjects who underwent an unpredictable acute emotional
      stress (e.g. sudden death of a loved one) compared with 14 controls who did not.
      Probands were profoundly stressed as assessed 10 days after bereavement by their
      scores on the Hamilton Rating Scales of Anxiety and Depression,
      adrenocorticotropin and cortisol plasma concentrations, and non-suppression in
      response to dexamethasone. Functional alterations of immune parameters, such as
      responsiveness of peripheral blood lymphocytes to mitogens, were found 40 days
      after bereavement. Despite a normal number of circulating lymphocyte subsets, the
      functional activity of natural killer (NK) cells was markedly reduced at day 40.
      Changes in the intracellular concentration of beta-endorphin in peripheral blood
      mononuclear cells correlated with anxiety and depression scores. Controls showed
      no changes in psychometric, endocrine and immune measures during the 6-month
      study. Cluster analysis revealed two groups of bereaved subjects with different
      patterns of immune and endocrine changes: (1) Five subjects, characterized by
      harm-avoidant temperament and long-lasting dysphoric mood, showed reduced
      responsiveness of peripheral blood lymphocytes to mitogens, decreased NK cell
      activity and non-suppression in response to dexamethasone that persisted for 6
      months. (2) Nine subjects showed significant changes only during the early phase
      after bereavement. Our data suggest that the immunological consequences of stress
      do not simply overlap with psychological and endocrine alterations, and are
      particularly severe and long-lasting in a subgroup of subjects, indicating the
      importance of individual variability in the capacity to cope with stress.

PMID- 14656450
TI  - REM sleep reduction, mood regulation and remission in untreated depression.
AB  - The contribution of increased rapid eye movement (REM) pressure through repeated,
      mild, reduction of (REM) sleep to remission from untreated depression was studied
      over a 5-month period in 20 depressed and 10 control volunteers. Sixty percent of
      the depressed subjects were in remission at the end of the study. Sixty-four
      percent of the variance in remission could be accounted for by four variables:
      the initial level of self-reported symptoms, the reported diurnal variability in
      mood, the degree of overnight reduction in depressed mood following interruptions
      of REM sleep and the quality of dream reports from these awakenings. Increased
      REM pressure is beneficial for those who are able to construct well-organized
      dreams.

PMID- 14656451
TI  - Coping behavior in depressed patients: a longitudinal study.
AB  - The relationship of coping behavior to outcome in depressed patients was
      examined. Subjects (n=105) with major depressive disorder (n=85), depressive
      disorder not otherwise specified (n=7) or major depressive disorder with axis I
      comorbidity (n=13) were followed for 6 months. Their coping behavior (i.e.
      rumination, active distraction, cognitive distraction and dangerous activities)
      was defined using the Comprehensive Assessment List for Affective Disorders.
      Based on their Hamilton Rating Scale for Depression (HRSD) scores at 6 months,
      the patients were categorized as having had a good or a poor outcome. Severity of
      depression and coping behavior were similar among the three diagnostic groups. At
      baseline assessment, coping behavior was not correlated with either HRSD score or
      age. However, males were significantly more likely to be engaged in dangerous
      activity as a coping behavior than females. Patients with a good outcome at 6
      months were significantly more likely to use rumination as a coping behavior
      while patients with a poor outcome were significantly more likely to use
      dangerous activity. Multiple regression analysis confirmed this finding,
      indicating that rumination and dangerous activity were significant predictors of
      outcome at 6 months. Rumination might be associated with good outcomes in
      depressed patients while dangerous activity might be associated with poor
      outcomes.

PMID- 14656452
TI  - Cognitive deficits are associated with functional impairment in severely
      depressed patients.
AB  - Cognitive deficits have been associated with poorer function and quality of life
      (QOL) in schizophrenia, but no similar findings have been confirmed in persons
      with major depressive episode (MDE). We investigated whether cognitive deficits
      were associated with detrimental effects on the QOL of persons with primary MDE.
      Seventy-seven non-demented adults with MDE underwent evaluations of mood,
      cognition and QOL. Cognition was assessed with the Mini-Mental State Exam, and
      delayed recall on the Rey Auditory Verbal Learning Task and the Rey Figure. QOL
      assessments included instrumental activities of daily living (IADL), activities
      of daily living (ADL), and satisfaction in role functioning and relationships.
      Univariate correlation and regression models were used to find those mood and
      cognitive variables most closely related to each QOL dimension. ADL function and
      satisfaction with role functioning and relationships were most closely related to
      depression severity and age. IADL functioning, however, was most closely
      associated with global cognition. This study did not take into account the
      physical health of the participants, and all the participants were seriously ill
      with depression. Thus, the results may not apply to persons with less severe MDE.
      Antidepressant treatments that preserve or enhance global cognition in addition
      to relieving core depressive symptoms may lead to the best functional outcomes.

PMID- 14656453
TI  - Heart rate and QT interval variability: abnormal alpha-2 adrenergic function in
      patients with panic disorder.
AB  - Anxiety disorders are associated with an increase in cardiovascular mortality.
      Studies using heart rate (HR) and QT interval variability measures suggest a
      decreased cardiac vagal function and a relatively increased sympathetic function
      in anxiety. This is important, as increased sympathovagal balance is associated
      with life-threatening arrhythmias. Several studies have shown that panic disorder
      is associated with an increased sensitivity to yohimbine and a blunted growth
      hormone response to clonidine, which are alpha-2 adrenoceptor antagonist and
      agonist, respectively. This study investigated the changes in QTvi (QT variance
      corrected for mean QT interval squared/HR variance corrected for mean HR squared)
      during placebo, oral clonidine (150 mg) and oral yohimbine (20 mg) in a double
      blind design in 12 normal controls and 19 patients with panic disorder. HR and QT
      variability measures, especially QTvi, were obtained before and after the
      administration of these drugs to patients in supine and standing postures. As
      expected, patients with panic disorder became more anxious after yohimbine. In
      addition, the patients had a significant increase in QTvi after yohimbine and a
      significant decrease in QTvi after clonidine, which was not seen in the control
      group. The decreased anxiety after placebo was associated with decreased QTvi in
      patients. This study supports the previous reports of an abnormal sensitivity of
      alpha-2 adrenergic receptors in patients with panic disorder compared to controls
      and partly explains the association of increased cardiovascular mortality with
      conditions of anxiety. QTvi, a non-invasive indicator of cardiac repolarization
      lability, appears to be a useful tool to study cardiac sympathetic function.

PMID- 14656454
TI  - An empirical assessment of post-treatment alcohol consumption.
AB  - Substance abuse treatment programs have long contended that any post-treatment
      alcohol use is indicative of relapse. Recent studies, however, suggest more
      inclusive definitions. Zweben and Cisler (1996, 1999) consider both the drinking
      quantity and negative drinking consequences. Their proposed cutoffs integrate the
      1995 NIAAA guidelines for sensible and high risk drinking levels with the
      objective assessment of drinking-related consequences into the definition of
      relapse. Our study applied this model to a group of detoxified alcoholics in a
      post-treatment followup project. We asked if: (1) Zweben and Cisler's drinking
      categories could be found in our sample; (2) whether subgroups defined by post
      treatment drinking patterns differed with respect to their pre-treatment alcohol
      consumption levels, years of alcoholic drinking and drinking related problems;
      and (3) whether post-treatment drinking patterns were associated with
      differential psychosocial functioning at followup. Thirteen percent of the total
      sample (N=61) was found to meet Zweben and Cisler's moderate drinking category;
      34% were abstinent, 27% heavy drinkers and 13 participants (26%) were
      unclassifiable. At treatment completion (T1), those who became moderate drinkers
      reported higher levels of self-confidence, but were otherwise similar to both
      abstainers and heavy drinkers. At followup (T2), approximately 1 year after
      initial testing (T1), groups differed on measures of emotional discharge,
      avoidance and logical coping skills and information seeking, suggesting a
      possible association between post-treatment drinking patterns and psychosocial
      functioning.

PMID- 14656455
TI  - Simultaneous detection of enteric viruses by multiplex real-time RT-PCR.
AB  - A multiplex real-time RT-PCR protocol for the simultaneous detection of
      noroviruses ("Norwalk-like viruses") of genogroups I and II, human astroviruses
      and enteroviruses is described. The protocol was developed and evaluated using
      the LightCycler and corresponding SYBR Green reagents. New primers were designed
      within conserved genome regions to optimize the detection range of virus subtypes
      of each genus. To enable the development of a multiplex PCR assay within one tube
      (capillary), similar mastermix- and cycling-conditions were respected for each
      individual primer system. Subsequent melting curve analysis allowed the
      determination of possible dual-contaminations of entero- and noro- or
      astroviruses by the formation of dual peaks. Special care was taken to minimize
      the loss of sensitivity, since the detection of small viral contaminations is a
      crucial parameter especially for food analysis. The multiplex assay was compared
      successfully to the single SYBR Green assay, and revealed to be at least 10 times
      more sensitive than the one obtained with an endpoint PCR thermocycler protocol
      published previously.

PMID- 14656456
TI  - Hepatitis B virus genotyping based on cluster analysis of the region involved in
      lamivudine resistance.
AB  - Hepatitis B virus (HBV) genotyping and treatment resistances analysis provide key
      information for the study of infected patients. Among the existing HBV genotyping
      methods, restriction fragment length polymorphism (RFLP) based methods are used
      widely, but HBV genetic variability may lead to wrong results. A simple method
      for HBV genotyping is described. This single assay provides information related
      to both genotyping and lamivudine resistance. measuring genotyping reliability. A
      short region including the YMDD motif of the polymerase gene was analyzed using
      cluster analysis of 55 isolates. To discriminate the seven HBV genotypes, a
      selected fragment was used as representative of each genotype (consensus
      sequences). Comparison between complete genomes from GenBank and from the YMDD
      analysis using PHILIP package was used for method testing. Sequencing of 102
      different serum samples was carried out, and the results were compared with
      representative sequences. Consensus sequences were chosen corresponding to the
      different HBV genotypes. Statistical comparison between our method and others
      gives more than 90% of coincidences with a critical level of 0.056. Comparison
      between RFLP and the method described gives 3% of discordance results and 3% of
      untypables samples by RFLP. All the discordant results observed had a change in
      the pre-S sequence which introduced a new restriction site.

PMID- 14656457
TI  - A simple mathematical formula for stoichiometry quantification of viral and
      nanobiological assemblage using slopes of log/log plot curves.
AB  - In nanotechnology, biomolecular assemblies serve not only as model systems for
      the construction of nanodevices, but they can also be used directly as templates
      for the formation of nanostructures. Biological nano-building blocks can either
      be isolated as complete functional units from living cells or viruses (biological
      "Top down" approach) or formed by biomolecular assembly from recombinant or
      synthetic components ("Bottom up" approach). In both cases, rational design of
      nanostructures requires knowledge of the stoichiometry of the biological
      structures, which frequently occur as multimers, i.e., the morphological complex
      is composed of multiple copies of one or more macromolecules. In this paper, a
      method is described for the stoichiometric quantification of molecules in bio
      nanostructures. The method is based on using dilution factors and relative
      concentrations rather than absolute quantities, which are often difficult to
      determine, especially in short-lived assembly intermediates. The approach
      exploits the fact that the larger the stoichiometry of the component is, the more
      dramatic is the influence of the dilution factor (decrease in concentration) on
      the reaction. We established and used the method to determine the stoichiometry
      of components of bacterial virus phi29. The log of dilution factors was plotted
      against the log of reaction yield. The stoichiometry Z was determined with the
      equation Z=-1.58+2.4193T-0.001746T(2) [T in (0,1000), or 90 degree angle alpha in
      (0 degrees, 89.9 degrees )], where T is the slope of the curve (tangent of 90
      degree angle alpha, which is the angle between the x-axis and the concentration
      dependent curve). Z can also be determined from a standard table given in this
      report. With the bacteriophage phi29 in vitro assembly system, up to 5x10(8)
      infectious virions per ml can be assembled from 11 purified components, giving
      our method a sensitivity of nine orders of magnitude. We confirmed the
      stoichiometries of phi29 components that were determined previously with
      microscopic approaches. The described method also responded to programmed
      stoichiometry changes, which were generated by assembling the phi29 DNA packaging
      motor from modified pRNA (DNA-packaging RNA) molecules forming a trimer of dimers
      or a dimer of trimers, instead of the wild-type hexamer.

PMID- 14656458
TI  - An alternative genetic method to test essential vaccinia virus early genes.
AB  - The vaccinia virus F11L gene product was identified during search for additional
      factors involved in the control of post-replicative viral gene transcription
      elongation. F11L is a 1065 base pairs (354 aminoacids) gene expressed early
      during infection with no attributed function. The F11L gene is conserved in many
      but not all poxviruses. The essential presence of the F11L gene was tested using
      two different genetic methods. F11L gene disruption by insertion of a selectable
      cassette containing the Escherichia coli guanine phosphoribosyl transferase gene
      driven by the viral early-late 7.5K transcriptional promoter resulted exclusively
      in recombinant viruses containing both the wild type and disrupted alleles,
      indicating that the F11L gene was essential. However, an alternative test, using
      transient dominant selection to insert nonsense mutations into the F11L gene,
      proved that the F11L gene was non-essential for growth in culture. These
      experiments suggest that misleading results can be obtained using gene
      insertional mutagenesis as a test of essential presence of the gene. The
      experiments also provide genetic data on the probability of co-insertion of
      linked mutations in vaccinia virus genome using transient dominant selection.

PMID- 14656459
TI  - A dengue-2 Envelope fragment inserted within the structure of the P64k
      meningococcal protein carrier enables a functional immune response against the
      virus in mice.
AB  - A gene fragment encoding for the amino acids (aa) 286-426 from the dengue
      Envelope (E) protein was expressed in Escherichia coli as two forms of fusion
      proteins. In one case, the E fragment was fused to the first 45 aa of the P64k
      protein from Neisseria meningitidis (PD2) while, in the other, it was inserted
      within the lipoil-binding domain of the aforementioned bacterial protein (PD3).
      PD2 was obtained as insoluble form within the cytoplasm of the bacteria while PD3
      was distributed equally as soluble and insoluble forms. The insoluble forms of
      each protein as well as the soluble fraction of PD3 were semipurified to test the
      antigenicity and the immunogenicity in mice. The forms containing the entire P64k
      protein exhibited the highest recognition with different polyclonal and
      monoclonal antibodies. Consequently, the neutralizing antibodies elicited by the
      recombinant proteins were higher in the case of PD3 forms than with PD2,
      independently of the solubility status. In addition, mice inoculated with the
      semipurified insoluble form of PD3 were partially protected against lethal
      challenge with dengue-2 virus, administered by intracerebral inoculation. The
      results suggested the folding and carrier capacity of the P64k protein over the E
      fragment, converting PD3 as an attractive vaccine candidate against dengue-2
      virus.

PMID- 14656460
TI  - Linear amplification followed by single primer polymerase chain reaction to
      amplify unknown DNA fragments: complete nucleotide sequence of Oropouche virus M
      RNA segment.
AB  - The whole nucleotide sequence of Oropouche virus medium (M) RNA, Orthobunyavirus
      genus, Bunyaviridae family, was obtained using a new genomic amplification
      method. This method is based on the use of a single and specific primer of high
      melting temperature in a linear amplification (LA), followed by a single primer
      polymerase chain reaction (LASP-PCR). The LASP-PCR was used to walk along the
      Oropouche M RNA completing the sequence in seven successive walks. The amplicons
      obtained in each walking step ranged from 300 to 1100 bp; however, amplicons of
      up to 3970 bp was obtained when the extension time of the LASP-PCR was increased
      from 120 to 270 s. This method was tested successfully for Escherichia coli and
      cytomegalovirus obtaining amplicons of up to 2130 and 6500 bp, respectively,
      indicating that it can be applied to amplify unknown DNA sequences adjacent to a
      short stretch of known sequence of more complex genomes.

PMID- 14656461
TI  - Detection of white spot syndrome virus in shrimp by loop-mediated isothermal
      amplification.
AB  - Loop-mediated isothermal amplification (LAMP) method is a novel, sensitive and
      rapid technique which can be applied for disease diagnosis in aquaculture. Using
      the LAMP method, a highly specific and sensitive diagnostic system for white spot
      syndrome virus (WSSV) detection was designed. A set of four primers, two outer
      and two inner primers, were designed from WSSV genome DNA. Reaction time and
      temperatures were optimized for 60 min at 65 degrees C, respectively. The
      detection limit (DL) using the LAMP method was up to 1 fg, when compared to 10 fg
      by nested polymerase chain reaction (PCR). Thus, standardized LAMP procedure was
      used to detect the presence of WSSV in the heart, stomach and lymphoid organ from
      infected shrimp. The study has developed a diagnostic procedure which is a rapid
      and highly sensitive for WSSV detection in shrimp.

PMID- 14656462
TI  - Development of nested RT-PCR for the detection of swine hepatitis E virus in
      formalin-fixed, paraffin-embedded tissues and comparison with in situ
      hybridization.
AB  - Swine hepatitis E virus (HEV) was detected in formalin-fixed, paraffin-embedded
      tissues from naturally infected pigs by nested reverse transcription-polymerase
      chain reaction (RT-PCR). The results for seminested RT-PCR were compared with
      those determined by in situ hybridization. The results obtained show that use of
      xylene deparaffinization, digestion with proteinase K followed by nested RT-PCR
      is a reliable detection method. Swine HEV nucleic acid was detected in formalin
      fixed, paraffin-embedded hepatic tissues from 40 pigs. Distinct positive signals
      for swine HEV were obtained in the same hepatic tissues by in situ hybridization.
      Swine HEV nucleic acid was localized to the cytoplasm of hepatocytes and had a
      granular staining pattern. The rate of agreement between nested RT-PCR and in
      situ hybridization for the detection of swine HEV in formalin-fixed, paraffin
      embedded hepatic tissues was 100%.

PMID- 14656463
TI  - Enhanced isolation of low frequency herpes simplex virus recombinants using green
      fluorescent protein and FACS.
AB  - The generation of recombinant herpes simplex virus to study the effect of
      engineered mutations on viral biology relies on the isolation of recombinants
      from a mixed population of viruses following a marker transfer procedure.
      Currently, the E. coli lacZ or green-fluorescent protein (GFP) genes are most
      frequently used as markers for isolation and isolation of recombinants relies on
      visual screening of plaques. Alternatively, novel restriction site changes can be
      inserted into a gene followed by screening of individual plaques for the novel
      change. These methods are inefficient when the frequency of recombinants in the
      pool of viruses is low. Using GFP as a selection marker, a FACS procedure that
      results in a substantial enrichment of the frequency of recombinants is
      described. Cells were infected at a multiplicity of infection (MOI) of 1.0 in the
      presence of acyclovir and at 10h post-infection, either the GFP+ or GFP- cells
      were sorted by FACS, and the sorted cells were plated on fresh cells. After three
      rounds of selection, the frequency of GFP+ recombinants rose from 0.1 to 3-4%. A
      mutant virus with a GFP insertion in the US1 gene (alpha22 protein) was generated
      and then used to isolate a virus with a mutation, Y116C, in the alpha22 protein.

PMID- 14656464
TI  - Generation and characterization of single-chain antibody fragments specific
      against transmembrane envelope glycoprotein gp46 of maedi-visna virus.
AB  - A single-chain antibody fragments (scFv) was developed directed against
      transmembrane envelope glycoprotein gp46 of the virus maedi-visna, by the
      application of the antibody phage display library. To get specific scFv binders,
      the library was panned against the biotinylated peptide of 20 amino acids
      corresponding to the principal immunodominant domain of gp46 protein. The number
      of positively binding scFvs was evaluated by scFv-phage ELISA, BstN1
      fingerprinting and DNA sequencing. The scFvs were expressed in soluble form and
      purified by immobilized metal affinity chromatography (IMAC) with a yield of 2
      2.5 mg/l. Two scFvs have shown to recognize gp46 and gp150 proteins in Western
      blot analysis. The scFvs also recognized the virus in infected cells as shown by
      immunofluorescence assay. The affinity of the obtained antibody fragments to gp46
      peptide was measured by surface plasmon resonance, and the resulting K(A) was in
      the 10(6)-10(7)lmol(-1) range. The application of characterized scFvs for
      expression as intrabodies in intracellular immunization against virus maedi-visna
      infection and for the diagnosis of this virus is discussed.

PMID- 14656465
TI  - Detection of bovine gammaherpesviruses by a nested duplex PCR.
AB  - The two bovine gammaherpesviruses (Alcelaphine herpesvirus 1, AlHV-1; Bovine
      herpesvirus 4, BoHV-4) are distributed worldwide in cattle populations. Since the
      animals are frequently infected latently with no or low seropositivity, a DNA
      based diagnostic method would be useful for surveys and detection of these
      viruses. In the present study a nested duplex PCR was established for the
      sensitive and specific simultaneous detection of both viruses. The primers were
      designed for the gene of the major capsid protein (ORF25). The assay did not
      amplify the capsid gene sequence of 10 related bovine herpesviruses and other
      gammaherpesviruses. The test was able to detect 1pfu (plaque forming unit) of
      AlHV-1 and BoHV-4. Among 146 clinical samples (lymph nodes and peripheral blood
      leukocytes, PBLs) 65 (44.52%) were found to be positives for AlHV-1 and 84
      (57.53%) for BoHV-4. This nested duplex PCR assay could serve as a useful
      diagnostic method for rapid, sensitive, specific simultaneous detection of the
      two bovine gammaherpesviruses.

PMID- 14656466
TI  - Immunological factors that affect the in vivo fate of T7 phage in the mouse.
AB  - Phage display is a powerful method to study organ and tissue specific addresses.
      As part of our studies on the in vivo panning of tissue-homing peptide libraries,
      we examined the survival of T7 phage in the blood of C57BL/6J mice to estimate
      the half-life of T7 phage and the factors responsible for its inactivation.
      Amplified and purified T7 phage particles with or without random peptide library
      inserts were injected intravenously into the tail vein of wild-type (C57BL/6J)
      and immunocompromized (C57BL/6J) female mice. In wild-type mice, both the parent
      phage as well as phage carrying a peptide library were eliminated quickly from
      the blood, with only approximately 1% survival of detectable infectious phage
      after 60 min of injection. In SCID (C57BL/6J-Prkdc(scid)) mice, phage titers were
      stable over the same period of time with or without peptide library, suggesting a
      role for either B- or T cells or both in phage inactivation. The presumed role of
      B cell was indicated by demonstration of stable phage in the B-cell deficient
      mouse (C57BL/10-Igh-6(tm1Cgn)). In other immunocompromized mice, the phage titers
      were unstable, similar to that found in wild-type mice. In no case, was there a
      difference between phage with or without random peptide library. These data
      indicate that the presence of random C-X7-C peptides on the T7 phage coat protein
      does not affect the clearance of the phage in murine blood. Most likely, host
      immune factors play a role in the neutralization of T7 phage in blood by reacting
      with B-cell dependent immunoglobin.

PMID- 14656467
TI  - Evaluation of three rapid tests for detection of antibodies to HIV-1 non-B
      subtypes.
AB  - Three rapid tests were evaluated for the detection of antibodies to HIV in 111
      plasma specimens (81 HIV-1 non-B subtypes, including 4 coinfections with HIV-2,
      30 HIV negative). The Determine HIV-1/2, Equipar HIV, and Multispot HIV-1/2 tests
      were 100% sensitive and specific for the detection of HIV-1 antibodies. Multispot
      showed 92.7% specificity for HIV-2.

PMID- 14656468
TI  - Quantitation of Taura syndrome virus by real-time RT-PCR with a TaqMan assay.
AB  - A real-time RT-PCR assay was developed using a TaqMan probe to detect and
      quantify Taura syndrome virus (TSV) in penaeid shrimp. A pair of RT-PCR primers,
      which amplify a 72 bp DNA fragment, and a TaqMan probe were selected from open
      reading frame 1 (ORF1) of the TSV genome. The primers and TaqMan probe used in
      this assay reacted with TSV isolates from Hawaii, Texas, Colombia, Mexico,
      Belize, Indonesia, and Thailand, but neither with RNA of healthy shrimp nor with
      an isolate of yellow head virus. A plasmid (pTSV-1) that contains the target TSV
      sequence was constructed and used to generate positive control RNA through in
      vitro transcription. The positive control RNA was used to demonstrate that the
      real-time RT-PCR assay has a detection limit of 100 copies and a log-linear range
      up to 10(8) copies of TSV RNA. This quantitative method was found to be highly
      reproducible, with low intra- and inter-assay variation. Coefficient of variation
      (CVs) values were 0.04-8.9 and 0.05-3.7%, respectively, for replicates within and
      among assays. This assay was used to quantify TSV in both acutely and chronically
      infected shrimp in a laboratory experiment. The quantities of TSV in the tissues
      of pleopods and gills were not significantly different, and there was no
      difference in TSV levels between the acutely and chronically infected groups.
      However, in the chronically infected shrimp, the quantities of TSV were one to
      two orders of magnitude higher in the lymphoid organ than in either gills or
      pleopods. This assay proved to be specific with high sensitivity, and it can be
      used to detect and quantify TSV in shrimp samples.

PMID- 14656470
TI  - Components of the anti-Mullerian hormone signaling pathway in gonads.
AB  - Anti-Mullerian hormone (AMH) is a member of the Transforming Growth Factor-beta
      (TGF-beta) family implicated in the regression of Mullerian ducts in male fetuses
      and in the development and function of gonads of both sexes. Members of the TGF
      beta family signal through two types of serine/threonine kinase receptors called
      type I and type II, and two types of Smad proteins, receptor-regulated Smad (R
      Smad) and common Smad, Smad4. Components of the AMH signaling pathway have been
      identified in gonads and gonadal cell lines. The AMH type II receptor is highly
      specific. In contrast, the identity of the AMH type I receptor is not clear;
      three type I receptors of Bone Morphogenetic Proteins (BMPs), Alk2, Alk3 and Alk6
      may transduce AMH signals, but none of them has all the characteristics of an AMH
      type I receptor. AMH activates BMP-specific R-Smads and reporter genes.

PMID- 14656469
TI  - AMH induces mesonephric cell migration in XX gonads.
AB  - Migration of mesonephric cells into XY gonads is a critical early event in testis
      cord formation. Based on the fact that anti-Mullerian hormone (AMH) can induce
      testis cord formation in XX gonads, we investigated whether AMH plays a role in
      the induction of cell migration. Addition of recombinant AMH induced mesonephric
      migration into XX gonads in culture. AMH-treated XX gonads displayed increased
      vascular development and altered morphology of the coelomic epithelium, both
      features of normal testis differentiation. AMH did not induce markers of Sertoli
      or Leydig cell differentiation. We examined early testis development in Amh
      deficient mice, but found no abnormalities, suggesting that any function AMH may
      have in vivo is redundant. Other transforming growth factor (TGF-beta) family
      proteins, bone morphogenetic proteins (BMP2 and BMP4) show similar inductive
      effects on XX gonads in culture. Although neither BMP2 nor BMP4 is expressed in
      embryonic XY gonads, our findings suggest that a TGF-beta signalling pathway
      endogenous to the XY gonad may be involved in regulation of mesonephric cell
      migration. The factors involved in this process remain to be identified.

PMID- 14656471
TI  - Genetic studies of the AMH/MIS signaling pathway for Mullerian duct regression.
AB  - Anti-Mullerian hormone (AMH)/Mullerian-inhibiting substance (MIS) is a member of
      the transforming growth factor-beta (TGF-beta) superfamily. Like other TGF-beta
      family members, AMH is likely to signal through two transmembrane
      serine/threonine kinase receptors. Whereas the AMH type II receptor has been
      clearly defined, only recently has there been evidence about the identity of the
      AMH type I receptor for Mullerian duct regression in vivo. We generated a new cre
      mouse line expressing the recombinase in AMH target cells. This line was then
      used to conditionally inactivate the Bmpr1a gene in the Mullerian duct, resulting
      in males with a uterus. Thus, Bmpr1a plays an essential role in the process of
      Mullerian duct regression. To investigate the role of Bmpr1a in granulosa cells,
      we took advantage of transgenic mice overexpressing human AMH. Surprisingly,
      these transgenic females that were also conditionally mutant for Bmpr1a in the
      Mullerian duct had no uterus. These results suggest that when AMH is
      overexpressed, other TGF-beta family type I receptors can potentially transduce
      AMH signals.

PMID- 14656472
TI  - AMH/MIS: what we know already about the gene, the protein and its regulation.
AB  - (AMH/MIS) was first suggested by Jost, more than Four decades before this gonadal
      glycoprotein was purified and its gene and promoter sequenced. In mammals, AMH
      expression is triggered by SOX9 in Sertoli cells at the onset of testicular
      differentiation, and regulated by SF1, GATA factors, WT1, DAX1 and FSH. Ovarian
      granulosa cells also secrete AMH from late foetal life. In males, AMH is secreted
      into the bloodstream at high levels until puberty when it is down-regulated by
      androgens and meiotic germ cells and its directional secretion switches from the
      basal compartment to the seminiferous tubule lumen. In birds and reptiles, AMH
      expression shows particular features. Serum AMH determination is useful to study
      testicular function in boys and in patients with gonadal tumours. AMH levels in
      seminal and follicular fluid may also be of clinical use.

PMID- 14656473
TI  - Unsolved problems in male physiology: studies in a marsupial.
AB  - Testicular androgens induce formation of the male urogenital tract in all
      mammals. In marsupials male development occurs after birth and over a prolonged
      period. For example, in the tammar wallaby virilization of the Wolffian ducts
      begins by day 20, prostate formation begins about day 25, and phallic development
      starts after day 80 of pouch life. Between days 20 and 40 5alpha-androstane
      3alpha,17beta-diol (5alpha-adiol) is formed in tammar testes and secreted into
      plasma. Administration of 5alpha-adiol to pouch young females induces urogenital
      sinus virilization by day 40 and formation of a mature male prostate and phallus
      by day 150. 5alpha-Adiol is synthesized in pouch young testes by two pathways,
      one involving testosterone and dihydrotestosterone and the other 5alpha-pregnane
      3alpha,17alpha-diol-20-one and androsterone as intermediates, both utilizing
      steroid 5alpha-reductase. In target tissues 5alpha-adiol acts via the androgen
      receptor after conversion to dihydrotestosterone but may have other actions as
      well. Whether 5alpha-adiol plays a role in male development in placental mammals
      is uncertain.

PMID- 14656474
TI  - Enhanced purification and production of Mullerian inhibiting substance for
      therapeutic applications.
AB  - It is almost 60 years since Prof. Alfred Jost reported the seminal observations
      regarding Mullerian inhibiting substance (MIS). His experiments clearly showed
      that a testicular product other than testosterone, a Mullerian inhibitor, was
      responsible for Mullerian duct regression. Twenty-five years later Dr. Picon
      established an organ culture assay which paved the way for the initial studies
      into the biochemistry and biology of Mullerian inhibiting substance, also known
      as Anti-Mullerian hormone (AMH), undertaken first in Dr. Nathalie Josso's
      Laboratory in Paris then in our own laboratory in Boston. Purification of MIS led
      to cloning the human gene and production of recombinant human (rhMIS). MIS is a
      140 kDa glycoprotein homodimer which is activated by a biosynthetic protease,
      cleaving MIS into an aminoterminus (110 kDa) and a carboxyterminus (25 kDa). The
      latter domain is sufficient for biological activities. MIS functions by
      interacting with two receptors; a type II binds the hormone and at type I that
      initiates downstream signaling. The MIS type II receptor has been cloned and
      functionally confirmed as distinct from that of other members of the TGFbeta
      superfamily. MIS can employ a number of type I receptors (ALK2, ALK3, ALK6) and
      BMP receptor specific SMADS 1, 5, and 8 in various tissue specific contexts. Cell
      lines derived from human ovarian, breast, and prostate tumors, and from rodent
      Leydig cell tumors, which respond to MIS in growth inhibition assays, all express
      the MIS type II receptor. A variety of signal transduction pathways are
      associated with the grown inhibition mediated by MIS. For example, breast and
      prostate cancer cell lines use a MIS-mediated NFkappaB pathway leading to G1
      arrest and apoptosis. The ovarian cancer cell lines employ a pathway which
      enhances p16, modulates the E2Fs, and induces apoptosis. These signal
      transduction events can establish new rational treatment strategies to complement
      the growth inhibitory effects mediated by MIS. These combination strategies are
      being tested in vitro, and where appropriate will be tested in vivo using the
      highly purified MIS preparations, prior to use in early human clinical trials.

PMID- 14656475
TI  - Mullerian Inhibiting Substance induces NFkB signaling in breast and prostate
      cancer cells.
AB  - The MIS type II receptor is expressed at high levels in the Mullerian duct and in
      Sertoli cells and granulosa cells of the embryonic and adult gonads. The presence
      of MIS type II and type I receptors in tissues and cell lines derived from breast
      and prostate suggests that the prostate and mammary glands may be additional
      targets for MIS action. In both breast and prostate cancer cells, MIS activated
      NFkB DNA binding activity and induced IEX-1, an immediate early gene which
      regulates cell growth and apoptosis. Exposure of cells to MIS inhibited growth by
      increasing the fraction of cells in the G1 phase of the cell cycle and by
      inducing apoptosis. These results suggest that MIS may be a putative mediator of
      growth regulatory signals in the breast and prostate.

PMID- 14656476
TI  - Hypogonadotropic hypogonadism as a model of post-natal testicular anti-Mullerian
      hormone secretion in humans.
AB  - The pituitary gonadotropins are the main regulators of testicular hormonal
      secretion in humans. Hypogonadotropic hypogonadism (HH), characterized by the
      absence of secretion of endogenous gonadotropins is therefore a convenient model
      to asses the respective effects of luteinizing hormone (LH) (or human chorionic
      gonadotropin (hCG)), exogenous testosterone (T) and FSH on gonadal function. In
      order to investigate the hormonal control of AMH secretion in man, serum AMH
      levels were measured in adult patients with congenital HH (CHH) and with post
      pubertal acquired HH (AHH) either untreated, during hCG or T therapy. In
      untreated CHH patients, serum AMH levels were significantly higher than in normal
      men and similar to those previously reported in prepubertal boys indicating the
      absence of pubertal maturation of Sertoli cells. In men with AHH, serum AMH
      levels were also significantly increased when compared to healthy men, but less
      than in CHH because a persistent testicular T secretion in these patients with
      less complete gonadotropin deficiency. The high AMH levels in AHH suggest that
      the post-pubertal suppression of AMH is a reversible phenomenon. In HH patients,
      hCG treatment induced an increase of plasma T associated with a dramatic decrease
      of serum AMH, whereas the similar increase in plasma T levels obtained with
      exogenous T induced only a partial decrease of serum AMH. This dissociation was
      related to the higher intratesticular T induced by hCG. Taken together, our
      results confirms the clinical relevance of previous data obtained in rodent
      models concerning the hormonal regulation of AMH secretion.

PMID- 14656477
TI  - Anti-Mullerian hormone levels in serum from human foetuses and children: pattern
      and clinical interest.
AB  - Serum anti-Mullerian hormone (AMH) determination has been used to investigate
      gonadal development and abnormal sexual differentiation, but until recently, it
      was based on assays developed by specialized laboratories. A short time ago, a
      sensitive assay kit was developed commercially (Immunotech-Beckman Coulter) for
      clinical use. With this method, we established usual levels of serum AMH in
      fetuses, newborns, and pre-pubertal children, and evaluated the clinical value of
      this assay. AMH measurement required only 25 microl of sample and could be
      performed within 3 h. In females, AMH emerged after birth at low levels (median:
      4 ng/ml). In males, AMH levels remained stable during fetal life (median: 44.4
      ng/ml), peaked in the first months of life to reach a median of 124.7 ng/ml, then
      fell with wide individual variations. Cord blood AMH levels at birth may be
      useful to investigate ambiguous genitalia suspected prenatally. In children with
      isolated microphallus or hypospadias, decreased AMH values are in favor of testis
      dysfunction. When testes cannot be palpated, a single determination of serum AMH
      levels can distinguish between anorchia and cryptorchidism.

PMID- 14656478
TI  - AMH signaling: from receptor to target gene.
AB  - Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance (MIS),
      is a member of the transforming growth factor beta (TGFbeta) superfamily and
      plays a crucial role during male sexual differentiation. Although the AMH type II
      receptor has been identified, the identity of the other signaling components has
      remained unknown. This review describes the identification of candidate AMH type
      I receptors and an AMH-target gene involved in Mullerian duct regression.

PMID- 14656479
TI  - Inborn errors of adrenal steroidogenesis.
AB  - Congenital adrenal hyperplasia (CAH) refers to a family of inherited disorders of
      adrenal steroidogenesis in which each disorder is characterized by a specific
      enzyme deficiency that impairs cortisol production by the adrenal cortex. The
      enzymes most commonly affected are 21-hydroxylase (21-OH), 11beta-hydroxylase,
      3beta-hydroxysteroid dehydrogenase, and less often, 17alpha-hydroxylase/17,20
      lyase and cholesterol desmolase. Many of the corresponding genes for the
      described enzymes have been isolated and characterized, and specific mutations
      causing CAH have been identified. In classical CAH (simple virilizing and salt
      wasting forms), androgen excess causes external genital ambiguity in newborn
      females and progressive postnatal virilization in both sexes. In nonclassical
      CAH, 21-OHD is partial and occurs with milder symptoms. A deficiency of 11beta
      Hydroxylase deficiency results in ambiguous genitalia in the newborn genetic
      female and androgen excess and hypertension in both males and females. In 3beta
      hydroxysteroid deficiency adrenal and gonadal androgen production is deficient
      resulting in incomplete genital development in genetic males and limited androgen
      affect in females. Two less frequent causes of CAH 17alpha-Hydroxylase/17,20
      lyase and cholesterol desmolase result in external female genitalia in both
      sexes. Hormonal diagnosis is described for each disorder.

PMID- 14656480
TI  - Anti-Mullerian hormone and its role in ovarian function.
AB  - Anti-Mullerian hormone (AMH) is expressed after birth in the ovary in the
      granulosa cells of healthy, small growing follicles. We have shown that AMH
      affects two important regulatory steps during folliculogenesis. At initial
      recruitment, AMH inhibits recruitment of primordial follicles into the growing
      pool, while at cyclic recruitment AMH lowers the FSH-sensitivity of follicles. In
      these ways, AMH plays an important role in regulation of ovarian follicle growth.
      AMH serum level is a strong candidate marker for ovarian reserve in women. In
      normo-ovulatory women, AMH serum levels correlated strongly with the number of
      antral follicles. In addition, AMH is a strong predictor for the number of
      oocytes retrieved in patients undergoing IVF treatment. The convenience of
      determination and its relative stable expression during the menstrual cycle
      indicate that further validation of the use of serum AMH is recommended as a
      clinical measure of ovarian reserve.

PMID- 14656481
TI  - MIS/AMH in the assessment of cryptorchidism and intersex conditions.
AB  - Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH),
      causes Mullerian duct involution during male sexual differentiation and also has
      a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific
      pattern of expression and its concentrations are sexually dimorphic in children;
      hence measurement of serum MIS/AMH helps in the evaluation of children with
      gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum
      MIS/AMH correlates with testicular tissue. A measurable value is predictive of
      undescended testes while an undetectable value is highly suggestive of anorchia.
      In minimally virilized phenotypic females, MIS/AMH helps differentiate between
      gonadal and non-gonadal causes of virilization. In children with intersex
      conditions, MIS/AMH values assist differential diagnosis: a value above the
      normal female range is predictive of testicular tissue, while an undetectable
      value is suggestive of absent testicular tissue. Thus, MIS/AMH is useful for
      delineating gonadal pathology and facilitates the differential diagnosis and
      management of children with diverse gonadal disorders.

PMID- 14656482
TI  - Inhibition of steroidogenesis in Leydig cells by Mullerian-inhibiting substance.
AB  - Mullerian-inhibiting substance (MIS), a member of the transforming growth factor
      beta family of cytokines that signal through a heteromeric complex of single
      transmembrane serine/threonine kinase receptors, is required for Mullerian duct
      regression and normal reproductive tract development in the male embryo. However,
      the continued expression of MIS at high levels in males until puberty and its
      induction in females after birth suggested other roles for MIS. Additionally,
      Leydig cell development and steroidogenic capacity and ovarian follicle
      recruitment were abnormal in MIS-knockout or MIS-overexpressing mice. We have
      shown that MIS inhibits the cAMP-induced expression of cytochrome P450 C17alpha
      hydroxylase/C17-20 lyase (Cyp17) mRNA both in vitro and in vivo. Our current
      efforts are to understand the molecular mechanisms regulating both MIS type II
      receptor (MISRII) expression and its signaling in rodent Leydig cell lines.
      MISRII expression in R2C cells requires both steroidogenic factor-1 and an
      unknown protein to bind to its proximal promoter in the context of 1.6 kb 5'
      flanking DNA. When bound by MIS, signaling by the receptor in MA-10 cells blocks
      the protein kinase A-mediated induction of Cyp17 expression by a cAMP regulatory
      element-binding protein independent mechanism. We continue to investigate the
      molecular mechanisms of MISRII expression and possible interactions between MIS
      regulated SMAD activation and cAMP signaling. These studies will provide a better
      understanding of the role played by MIS during postnatal life.

PMID- 14656483
TI  - Controlling cell fate by bone morphogenetic protein receptors.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional proteins that regulate the
      fate of different cell types, including mesenchymal and endothelial cells. BMPs
      inhibit myogenic differentiation, but promote the differentiation of mesenchymal
      cells into osteoblasts. Furthermore, endothelial migration and tube formation are
      stimulated by BMPs. Like other members of the transforming growth factor-beta
      (TGF-beta) superfamily, BMPs elicit their cellular effects via specific types I
      and II serine/threonine receptors. The activated BMP type I receptor
      phosphorylates specific receptor-regulated (R)-Smad proteins, which assemble into
      heteromeric complexes with common partner (Co)-Smad4. Heteromeric Smad complexes
      efficiently translocate into the nucleus, where they regulate the transcription
      of target genes. Inhibitors of differentiation (Id) are genes that are
      specifically induced by BMPs in tissues of different origin. Promoter analysis of
      Id1 indicates three distinct sequence elements that are sufficient and essential
      for efficient BMP-induced activation. Furthermore, recent studies reveal an
      important effector function for Id1 in various BMP-induced biological responses.

PMID- 14656484
TI  - Anti-Mullerian hormone, beta-catenin and Mullerian duct regression.
AB  - The embryo is initially sexually indifferent, and correct sexual development is
      dependent on gonadal hormone production. Thus, in the male embryo, anti-Mullerian
      hormone (AMH), secreted by the Sertoli cells of the testis, induces regression of
      the Mullerian duct, the anlagen of female reproductive tract. This hormone causes
      ductal epithelial regression through a paracrine mechanism originating in
      periductal mesenchyme and the cross-talk between the mesenchymal and epithelial
      layers accounts for the cranial-to-caudal pattern of Mullerian regression. Here,
      we review and discuss recent developments concerning the relationship of
      apoptosis of Mullerian duct to tissue remodeling, mesenchymal-epithelial
      interactions, and involvement of beta-catenin in AMH signaling in periductal
      mesenchyme. Determining the role of beta-catenin/LEF-1 signaling is critical for
      understanding AMH action during Mullerian duct regression.

PMID- 14656485
TI  - Proceedings of the 1st International Workshop on Anti-Mullerian Hormone/Mullerian
      Inhibiting Substance. Aix-en-Provence, France, 7-8 October 2002.

PMID- 14656486
TI  - Rule-base derivation for intensive care ventilator control using ANFIS.
AB  - In recent years, much research has been done on the use of fuzzy systems in
      medicine. The fuzzy rule-bases have usually been derived after extensive
      discussion with the clinical experts. This takes a lot of time from the clinical
      experts and the knowledge engineers. This paper presents the use of the adaptive
      neuro-fuzzy inference system (ANFIS) in rule-base derivation for ventilator
      control. The change of the inspired fraction of oxygen (FiO(2)) advised by eight
      clinical experts responding to 71 clinical scenarios was recorded. ANFIS and a
      multilayer perceptron (MLP) were then used to model the relationship between the
      inputs (the arterial oxygen tension (PaO(2)), FiO(2) and the positive end
      expiratory pressure (PEEP) level) and the change in FiO(2) suggested. Compared to
      a previous fuzzy advisor (FAVeM), both the ANFIS and the MLP were found to
      correlate with the clinicians' decision better (correlation coefficient of 0.694
      and 0.701, respectively compared to 0.630). A formerly developed model-based
      radial basis network advisor (RBN-MB) was used for comparison. Closed-loop
      simulations showed that the ANFIS, MLP and the RBN-MB's performance were
      comparable to the clinicians' performance (correlation coefficients of 0.852,
      0.962 and 0.787, respectively). The FAVeM's performance differed from the
      clinicians' performance (correlation coefficient of 0.332) but the resulting
      PaO(2) was still within safety limits.

PMID- 14656487
TI  - Fuzzy cluster analysis of high-field functional MRI data.
AB  - Functional magnetic resonance imaging (fMRI) based on blood-oxygen level
      dependent (BOLD) contrast today is an established brain research method and
      quickly gains acceptance for complementary clinical diagnosis. However, neither
      the basic mechanisms like coupling between neuronal activation and haemodynamic
      response are known exactly, nor can the various artifacts be predicted or
      controlled. Thus, modeling functional signal changes is non-trivial and
      exploratory data analysis (EDA) may be rather useful. In particular,
      identification and separation of artifacts as well as quantification of expected,
      i.e. stimulus correlated, and novel information on brain activity is important
      for both, new insights in neuroscience and future developments in functional MRI
      of the human brain. After an introduction on fuzzy clustering and very high-field
      fMRI we present several examples where fuzzy cluster analysis (FCA) of fMRI time
      series helps to identify and locally separate various artifacts. We also present
      and discuss applications and limitations of fuzzy cluster analysis in very high
      field functional MRI: differentiate temporal patterns in MRI using (a) a test
      object with static and dynamic parts, (b) artifacts due to gross head motion
      artifacts. Using a synthetic fMRI data set we quantitatively examine the
      influences of relevant FCA parameters on clustering results in terms of receiver
      operator characteristics (ROC) and compare them with a commonly used model-based
      correlation analysis (CA) approach. The application of FCA in analyzing in vivo
      fMRI data is shown for (a) a motor paradigm, (b) data from multi-echo imaging,
      and (c) a fMRI study using mental rotation of three-dimensional cubes. We found
      that differentiation of true "neural" from false "vascular" activation is
      possible based on echo time dependence and specific activation levels, as well as
      based on their signal time-course. Exploratory data analysis methods in general
      and fuzzy cluster analysis in particular may help to identify artifacts and add
      novel and unexpected information valuable for interpretation, classification and
      characterization of functional MRI data which can be used to design new data
      acquisition schemes, stimulus presentations, neuro(physio)logical paradigms, as
      well as to improve quantitative biophysical models.

PMID- 14656488
TI  - The application of fuzzy-based methods to central nerve fiber imaging.
AB  - This paper discusses the potential of fuzzy logic methods within medical imaging.
      Technical advances have produced imaging techniques that can visualize structures
      and their functions in the living human body. The interpretation of these images
      plays a prominent role in diagnostic and therapeutic decisions, so physicians
      must deal with a variety of image processing methods and their applications. This
      paper describes three different sources of medical imagery that allow the
      visualization of nerve fibers in the human brain: (1) an algorithm for automatic
      segmentation of some parts of the thalamus in magnetic resonance images based on
      the differences in myelin content in various thalamic subnuclei; (2) polarized
      light for classifying the 3D orientation of the nerve fibers at each point; and
      (3) confocal laser scanning microscopy (CLSM) for calculating semiquantitative
      variables for myelin content. Fuzzy logic methods were applied to analyze these
      pictures from low- to high-level image processing. The solutions presented here
      are motivated by problems of routine neuroanatomic research demonstrating fuzzy
      based methods to be valuable tools in medical image processing.

PMID- 14656489
TI  - Fuzzy epidemics.
AB  - The purpose of this paper is to provide a review of the current state of fuzzy
      logic theory in epidemiology, which is a recent area of research. We present four
      applications of fuzzy logic theory in epidemic problems, using linguistic fuzzy
      models, possibility measure, probability of fuzzy events and fuzzy decision
      making techniques. The results demonstrate that the applications of fuzzy sets in
      epidemiology is a very promising area of research. The final discussion sets the
      future stage of fuzzy sets application in epidemiology.

PMID- 14656490
TI  - A fuzzy cognitive map approach to differential diagnosis of specific language
      impairment.
AB  - This paper presents a computer-based model for differential diagnosis of specific
      language impairment (SLI), a language disorder that, in many cases, cannot be
      easily diagnosed. This difficulty necessitates the development of a methodology
      to assist the speech therapist in the diagnostic process. The methodology tool is
      based on fuzzy cognitive maps and constitutes a qualitative and quantitative
      computer model comprised of the experience and knowledge of specialists. The
      development of the model was based on knowledge from the literature and then it
      was successfully tested on four clinical cases. The results obtained point to its
      final integration in the future and to its valid contribution as a differential
      diagnosis model of SLI.

PMID- 14656492
TI  - Thinking of oneself as the same.

PMID- 14656493
TI  - The motor of cognition.

PMID- 14656495
TI  - Emerging selves: representational foundations of subjectivity.
AB  - A hypothetical evolutionary scenario is offered meant to account for the
      emergence of mental selves. According to the scenario, mental selves are
      constructed to solve a source-attribution problem. They emerge when internally
      generated mental contents (e.g., thoughts and goals) are treated like messages
      arising from external personal sources. As a result, mental contents becomes
      attributed to the self as an internal personal source. According to this view,
      subjectivity is construed outward-in, that is, one's own mental self is derived
      from, and is secondary to, the mental selves perceived in others. The social
      construction of subjectivity and selfhood relies on, and is maintained in,
      various discourses on subjectivity.

PMID- 14656496
TI  - Self-representation: searching for a neural signature of self-consciousness.
AB  - Human self-consciousness operates at different levels of complexity and at least
      comprises five different levels of representational processes. These five levels
      are nonconceptual representation, conceptual representation, sentential
      representation, meta-representation, and iterative meta-representation. These
      different levels of representation can be operationalized by taking a first
      person-perspective that is involved in representational processes on different
      levels of complexity. We refer to experiments that operationalize a first-person
      perspective on the level of conceptual and meta-representational self
      consciousness. Interestingly, these experiments show converging evidence for a
      recruitment of medial cortical and parietal regions during taking a first-person
      perspective, even when operating on different degrees of complexity. These data
      lend support for the speculative hypothesis, that there exist a neural signature
      for human self-consciousness that is recruited independent from the degree of
      representational complexity to be performed.

PMID- 14656497
TI  - How not to find the neural signature of self-consciousness.

PMID- 14656499
TI  - The emergence of a shared action ontology: building blocks for a theory.
AB  - To have an ontology is to interpret a world. In this paper we argue that the
      brain, viewed as a representational system aimed at interpreting our world,
      possesses an ontology too. It creates primitives and makes existence assumptions.
      It decomposes target space in a way that exhibits a certain invariance, which in
      turn is functionally significant. We will investigate which are the functional
      regularities guiding this decomposition process, by answering to the following
      questions: What are the explicit and implicit assumptions about the structure of
      reality, which at the same time shape the causal profile of the brain's motor
      output and its representational deep structure, in particular of the conscious
      mind arising from it (its "phenomenal output")? How do they constrain high-level
      phenomena like conscious experience, the emergence of a first-person perspective,
      or social cognition? By reviewing a series of neuroscientific results and
      integrating them with a wider philosophical perspective, we will emphasize the
      contribution the motor system makes to this process. As it will be shown, the
      motor system constructs goals, actions, and intending selves as basic
      constituents of the world it interprets. It does so by assigning a single,
      unified causal role to them. Empirical evidence demonstrates that the brain
      models movements and action goals in terms of multimodal representations of
      organism-object-relations. Under a representationalist analysis, this process can
      be conceived of as an internal, dynamic representation of the intentionality
      relation itself. We will show how such a complex form of representational
      content, once it is in place, can later function as a functional building block
      for social cognition and for a more complex, consciously experienced
      representation of the first-person perspective as well.

PMID- 14656500
TI  - Neurons don't represent.

PMID- 14656502
TI  - When the self represents the other: a new cognitive neuroscience view on
      psychological identification.
AB  - There is converging evidence from developmental and cognitive psychology, as well
      as from neuroscience, to suggest that the self is both special and social, and
      that self-other interaction is the driving force behind self-development. We
      review experimental findings which demonstrate that human infants are motivated
      for social interactions and suggest that the development of an awareness of other
      minds is rooted in the implicit notion that others are like the self. We then
      marshall evidence from functional neuroimaging explorations of the
      neurophysiological substrate of shared representations between the self and
      others, using various ecological paradigms such as mentally representing one's
      own actions versus others' actions, watching the actions executed by others,
      imitating the others' actions versus being imitated by others. We suggest that
      within this shared neural network the inferior parietal cortex and the prefrontal
      cortex in the right hemisphere play a special role in the essential ability to
      distinguish the self from others, and in the way the self represents the other.
      Interestingly, the right hemisphere develops its functions earlier than the left.

PMID- 14656503
TI  - Observing one's hand become anarchic: an fMRI study of action identification.
AB  - The self seems to be a unitary entity remaining stable across time. Nevertheless,
      current theorizing conceptualizes the self as a number of interacting sub-systems
      involving perception, intention and action (self-model). One important function
      of such a self-model is to distinguish between events occurring as a result of
      one's own actions and events occurring as the result of somebody else's actions.
      We conducted an fMRI experiment that compared brain activation after an abrupt
      mismatch between one's own movement and its visual consequences with an abrupt
      mismatch between one's own movement and somebody else's visually perceived hand
      movement. A right fronto-parietal network was selectively active during a sudden
      mismatch between one's own observed and performed hand action.

PMID- 14656504
TI  - The role of proprioception in action recognition.
AB  - This study aimed at evaluating the role of proprioception in the process of
      matching the final position of one's limbs with an intentional movement. Two
      experiments were realised with the same paradigm of conscious recognition of
      one's own limb position from a distorted position. In the first experiment, 22
      healthy subjects performed the task in an active and in a passive condition. In
      the latter condition, proprioception was the only available information since the
      central signals related to the motor command were likely to be absent. The second
      experiment was realised with a deafferented patient who suffers from a complete
      haptic deafferentation, including loss of proprioception. The results first argue
      in favour of a dominant role of proprioception in action recognition, but they
      also stress the possible role of central signals. The process of matching the
      final position of one's limbs with an intended movement and thus of action
      recognition would be achieved through a comparison process between the predicted
      sensory consequences of the action, which are stored in its internal model, and
      the actual sensory consequences of that action.

PMID- 14656505
TI  - Action identity: evidence from self-recognition, prediction, and coordination.
AB  - Prior research suggests that the action system is responsible for creating an
      immediate sense of self by determining whether certain sensations and perceptions
      are the result of one's own actions. In addition, it is assumed that declarative,
      episodic, or autobiographical memories create a temporally extended sense of self
      or some form of identity. In the present article, we review recent evidence
      suggesting that action (procedural) knowledge also forms part of a person's
      identity, an action identity, so to speak. Experiments that addressed self
      recognition of past actions, prediction, and coordination provide ample evidence
      for this assumption. The phenomena observed in these experiments can be explained
      by the assumption that observing an action results in the activation of action
      representations, the more so, when the action observed corresponds to the way in
      which the observer would produce it.

PMID- 14656506
TI  - Emergence of self and other in perception and action: an event-control approach.
AB  - The present paper analyzes the regularities referred to via the concept 'self.'
      This is important, for cognitive science traditionally models the self as a
      cognitive mediator between perceptual inputs and behavioral outputs. This leads
      to the assertion that the self causes action. Recent findings in social
      psychology indicate this is not the case and, as a consequence, certain cognitive
      scientists model the self as being epiphenomenal. In contrast, the present paper
      proposes an alternative approach (i.e., the event-control approach) that is based
      on recently discovered regularities between perception and action. Specifically,
      these regularities indicate that perception and action planning utilize common
      neural resources. This leads to a coupling of perception, planning, and action in
      which the first two constitute aspects of a single system (i.e., the distal-event
      system) that is able to pre-specify and detect distal events. This distal-event
      system is then coupled with action (i.e., effector-control systems) in a
      constraining, as opposed to 'causal' manner. This model has implications for how
      we conceptualize the manner in which one infers the intentions of another,
      anticipates the intentions of another, and possibly even experiences another. In
      conclusion, it is argued that it may be possible to map the concept 'self' onto
      the regularities referred to in the event-control model, not in order to reify
      'the self' as a causal mechanism, but to demonstrate its status as a useful
      concept that refers to regularities that are part of the natural order.

PMID- 14656507
TI  - Deluding the motor system.
AB  - How do we know that our own actions belong to us? How are we able to distinguish
      self-generated sensory events from those that arise externally? In this paper, I
      will briefly discuss experiments that were designed to investigate these
      questions. In particular, I will review psychophysical and neuroimaging studies
      that have investigated how we recognise the consequences of our own actions, and
      why patients with delusions of control confuse self-produced and externally
      produced actions and sensations. Studies investigating the failure of this 'self
      monitoring' mechanism in patients with delusions of control will be discussed in
      the context of the hypothesis that overactivity in the parietal cortex and the
      cerebellum contribute to the misattribution of an action to an external source.

PMID- 14656508
TI  - Self-consciousness, self-agency, and schizophrenia.
AB  - Empirical approaches on topics such as consciousness, self-awareness, or
      introspective perspective, need a conceptual framework so that the emerging,
      still unconnected findings can be integrated and put into perspective. We
      introduce a model of self-consciousness derived from phenomenology, philosophy,
      the cognitive, and neurosciences. We will then give an overview of research data
      on one particular aspect of our model, self-agency, trying to link findings from
      cognitive psychology and neuroscience. Finally, we will expand on pathological
      aspects of self-agency, and in particular on psychosis in schizophrenia. We show,
      that a deficient self-monitoring system underlies, in part, hallucinations and
      formal thought (language) disorder in schizophrenia. We argue, that self
      consciousness is a valid construct and can be studied with the instruments of
      cognitive and neuroscience.

PMID- 14656509
TI  - Being the agent: memory for action events.
AB  - Whoever paid the bill at the restaurant last night, will clearly remember doing
      it. Independently from the type of action, it is a common experience that being
      the agent provides a special strength to our memories. Even if it is generally
      agreed that personal memories (episodic memory) rely on separate neural
      substrates with respect to general knowledge (semantic memory), little is known
      on the nature of the link between memory and the sense of agency. In the present
      paper, we review results from two experiments investigating the effects of agency
      on both explicit and implicit memory traces. Performance of normal subjects is
      compared to that of schizophrenic patients in order to explore the role of
      awareness of action on memory. It is proposed that reliable first-person
      information is necessary to create a stable and coherent motor memory trace.

PMID- 14656510
TI  - Voluntary involuntariness: thought suppression and the regulation of the
      experience of will.
AB  - Participants were asked to carry out a series of simple tasks while following
      mental control instructions. In advance of each task, they either suppressed
      thoughts of their intention to perform the task, concentrated on such thoughts,
      or monitored their thoughts without trying to change them. Suppression resulted
      in reduced reports of intentionality as compared to monitoring, and as compared
      to concentration. There was a weak trend for suppression to enhance reported
      intentionality for a repetition of the action carried out after suppression
      instructions had been discontinued.

PMID- 14656511
TI  - Intentional action: conscious experience and neural prediction.
AB  - Intentional action involves both a series of neural events in the motor areas of
      the brain, and also a distinctive conscious experience that "I" am the author of
      the action. This paper investigates some possible ways in which these neural and
      phenomenal events may be related. Recent models of motor prediction are relevant
      to the conscious experience of action as well as to its neural control. Such
      models depend critically on matching the actual consequences of a movement
      against its internally predicted effects. However, it remains unclear whether our
      conscious experience of action depends on a precise matching process, or a
      retrospective inference that "I" must have been responsible for a particular
      event. We report an experiment in which normal subjects judged the perceived time
      of either intentional actions, involuntary movements, or subsequent effects
      (auditory tones) of these. We found that the subject's intention to produce the
      auditory tone produced an intentional binding between the perceived times of the
      subject's action and the tone. However, if the intention was interrupted by an
      imposed involuntary movement, followed by the identical tone, no such binding
      occurred. The phenomenology of intentional action requires an appropriate
      predictive link between intentions and effects, rather than a retrospective
      inference that "I" caused the effect.

PMID- 14656512
TI  - Intentionality as a constituting condition for the own self--and other selves.
AB  - Introspectively, the awareness of actions includes the awareness of the
      intentions accompanying them. Therefore, the awareness of self-generated actions
      might be expected to differ from the awareness of other-generated actions to the
      extent that access to one's own and to other's intentions differs. However, we
      recently showed that the perceived onset times of self- vs. other-generated
      actions are similar, yet both are different from comparable events that are
      conceived as being generated by a machine. This similarity raises two interesting
      possibilities. First we could infer the intentions of others from their actions.
      Second and more radically, we could equally infer our own intentions from the
      actions we perform rather than sense them. We present two new experiments which
      investigate the role of action effects in the awareness of self- and other
      generated actions by means of measuring the estimated onset time. The results
      show that the presence of action effects is necessary for the similarity of
      awareness of self- and other-generated actions.

PMID- 14656513
TI  - Five levels of self-awareness as they unfold early in life.
AB  - When do children become aware of themselves as differentiated and unique entity
      in the world? When and how do they become self-aware? Based on some recent
      empirical evidence, 5 levels of self-awareness are presented and discussed as
      they chronologically unfold from the moment of birth to approximately 4-5 years
      of age. A natural history of children's developing self-awareness is proposed as
      well as a model of adult self-awareness that is informed by the dynamic of early
      development. Adult self-awareness is viewed as the dynamic flux between basic
      levels of consciousness that develop chronologically early in life.

PMID- 14656514
TI  - Do I get what you get? Learning about the effects of self-performed and observed
      actions in infancy.
AB  - The present study investigated whether infants learn the effects of other
      persons' actions like they do for their own actions, and whether infants transfer
      observed action-effect relations to their own actions. Nine-, 12-, 15- and 18
      month-olds explored an object that allowed two actions, and that produced a
      certain salient effect after each action. In a self-exploration group, infants
      explored the object directly, whereas in two observation groups, infants first
      watched an adult model acting on the object and obtaining a certain effect with
      each action before exploring the objects by themselves. In one observation group,
      the infants' actions were followed by the same effects as the model's actions,
      but in the other group, the action-effect mapping for the infant was reversed to
      that of the model. The results showed that the observation of the model had an
      impact on the infants' exploration behavior from 12 months, but not earlier, and
      that the specific relations between observed actions and effects were acquired by
      15 months. Thus, around their first birthday infants learn the effects of other
      persons' actions by observation, and they transfer the observed action-effect
      relations to their own actions in the second year of life.

PMID- 14656515
TI  - The early origins of goal attribution in infancy.
AB  - We contrast two positions concerning the initial domain of actions that infants
      interpret as goal-directed. The 'narrow scope' view holds that goal-attribution
      in 6- and 9-month-olds is restricted to highly familiar actions (such as
      grasping). The cue-based approach of the infant's 'teleological stance', however,
      predicts that if the cues of equifinal variation of action and a salient action
      effect are present, young infants can attribute goals to a 'wide scope' of
      entities including unfamiliar human actions and actions of novel objects lacking
      human features. It is argued that previous failures to show goal-attribution to
      unfamiliar actions were due to the absence of these cues. We report a modified
      replication of Woodward (1999) showing that when a salient action-effect is
      presented, even young infants can attribute a goal to an unfamiliar manual
      action. This study together with other recent experiments reviewed support the
      'wide scope' approach indicating that if the cues of goal-directedness are
      present even 6-month-olds attribute goals to unfamiliar actions.

PMID- 14656516
TI  - Understanding infants' understanding of intentions: two problems of
      interpretation.

PMID- 14656518
TI  - The self and action in theory of mind research.
AB  - Research on children's developing theories of mind has contributed to our
      understanding of the developmental relation of self and action (1) by exploring
      the relation of the development of self knowledge to the development of knowledge
      of others' minds and (2) by investigating the relation between theory of mind
      development and the development of action control. We argue that evidence on
      theory of mind reasoning in children with deficient action control (ADHD
      diagnosed children) is especially relevant to the second issue and we present
      some first evidence supporting the bi-directional hypothesis, that is, the view
      that theory of mind leads to improved action control which in turn supports the
      ability to represent mental states on-line.

PMID- 14656519
TI  - Voltammetric behavior of 4',7-dimethoxy-3'-isoflavone sulfonic sodium and its
      enhancement determination in the presence of surfactant.
AB  - Voltammetric behavior of 4',7-dimethoxy-3'-isoflavone sulfonic sodium (DISS) was
      studied by linear sweep voltammetry and cyclic voltammetry. DISS caused two waves
      between pH 8.0 and 12.0. Above pH 8.0, the peak current of first wave Pc1 of DISS
      was enhanced in the presence of cetyltrimethylammonium bromide (CTAB). Based on
      this, a novel method for the determination of DISS was proposed. In Britton
      Robinson buffer solution (pH 11.7) containing 9.4 x 10(-6)mol L(-1) CTAB, the
      peak potential of first wave Pc1 of DISS was -1.59 V (vs standard saturated
      calomel electrode) and its first-order derivative peak current was proportional
      to the concentration of DISS in the range 5.0 x 10(-8)-6.0 x 10(-7)mol L(-1)
      (r=0.998). The detection limit was 1 x 10(-8)mol L(-1), which was 10 times lower
      than that of the corresponding reduction wave. The method was applied to the
      determination of DISS in synthetic samples.

PMID- 14656520
TI  - Pharmacokinetics of glycine-proline-glutamate, the N-terminal tripeptide of
      insulin-like growth factor-1, in rats.
AB  - Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like
      growth factor-1 and has been shown to be neuroprotective following ischemia
      induced brain injury. The pharmacokinetics of GPE were studied in adult rats
      since GPE is a candidate for use in neuroprotection therapies. To measure plasma
      concentrations of GPE a novel radioimmunoassay was developed whereby GPE was
      initially derivatized with Bolton and Hunter reagent before use in a standard
      homologous assay against the Bolton and Hunter iodinated form. The derivatized
      GPE radioimmunoassay showed a 83% recovery of unlabeled GPE and complete parallel
      displacement with rat plasma. The simplicity and speed of the assay described
      here indicate an exciting new use for a previously described technology. The
      pharmacokinetic studies were conducted in adult rats using a single bolus
      intravenous injection of GPE at 30 or 100 mg/kg and showed that GPE was rapidly
      cleared from the circulation. In addition, evidence of the route of the metabolic
      degradation of GPE is presented. The findings presented here are the first
      description of the pharmacokinetics of GPE and suggest that, because of its very
      short half-life in plasma, continuous intravenous infusion of GPE may be the
      preferred route of administration for use in future neuroprotection therapies.

PMID- 14656521
TI  - Development of melting temperature-based SYBR Green I polymerase chain reaction
      methods for multiplex genetically modified organism detection.
AB  - Commercialization of several genetically modified crops has been approved
      worldwide to date. Uniplex polymerase chain reaction (PCR)-based methods to
      identify these different insertion events have been developed, but their use in
      the analysis of all commercially available genetically modified organisms (GMOs)
      is becoming progressively insufficient. These methods require a large number of
      assays to detect all possible GMOs present in the sample and thereby the
      development of multiplex PCR systems using combined probes and primers targeted
      to sequences specific to various GMOs is needed for detection of this increasing
      number of GMOs. Here we report on the development of a multiplex real-time PCR
      suitable for multiple GMO identification, based on the intercalating dye SYBR
      Green I and the analysis of the melting curves of the amplified products. Using
      this method, different amplification products specific for Maximizer 176, Bt11,
      MON810, and GA21 maize and for GTS 40-3-2 soybean were obtained and identified by
      their specific Tm. We have combined amplification of these products in a number
      of multiplex reactions and show the suitability of the methods for identification
      of GMOs with a sensitivity of 0.1% in duplex reactions. The described methods
      offer an economic and simple alternative to real-time PCR systems based on
      sequence-specific probes (i.e., TaqMan chemistry). These methods can be used as
      selection tests and further optimized for uniplex GMO quantification.

PMID- 14656522
TI  - Development of an epitope tag for the gentle purification of proteins by
      immunoaffinity chromatography: application to epitope-tagged green fluorescent
      protein.
AB  - Polyol-responsive monoclonal antibodies (mAbs) are useful tools for the gentle
      purification of proteins and protein complexes. These are high-affinity mAbs that
      release the antigen in the presence of a nonchaotropic salt and a low-molecular
      weight polyhydroxylated compound (polyol). The epitope for the polyol-responsive
      mAb NT73, which reacts with Escherichia coli RNA polymerase, was located at the C
      terminus of the beta' subunit. Using recombinant DNA techniques, we have
      identified the epitope to be within the 13-amino-acid sequence SLAELLNAGLGGS and
      have developed an epitope tag that can be fused to a protein of interest for use
      as a purification tag. This epitope tag (designated Softag1) was fused to either
      the N or the C terminus of the green fluorescent protein. These tagged proteins
      were expressed in E. coli, and the tagged proteins were purified from the soluble
      fraction by a single-step immunoaffinity chromatography procedure. This approach
      extends the powerful technique of gentle-release immunoaffinity chromatography to
      many expressed proteins.

PMID- 14656523
TI  - A simplified method for inorganic phosphate determination and its application for
      phosphate analysis in enzyme assays.
AB  - A simplified method for inorganic phosphate determination has been developed. The
      method is sensitive, easy, economic, and applicable for estimation of phosphate
      released in both enzymatic and nonenzymatic reactions. A mixture of hydrazine
      sulfate and ascorbic acid was used as the reducing agent and the conditions for
      the development of the molybdenum blue color were optimized. Thus in the 4.0 ml
      assay system, 0.4 ml of the reducing agent solution containing 20 mg each of
      hydrazine sulfate and ascorbic acid per milliliter of 1.0 N H2SO4 gave a rapid
      optimum color development with absorption maximum at 820 nm. Color development
      showed a linear relationship up to 10 microg Pi concentration. Thus the method
      has a 2.5x higher range of Pi estimation than that of the Bartlett method. The
      molar extinction coefficient at 820 nm was higher than that obtained in the
      Bartlett procedure. Also the molybdenum blue color formed was stable up to 24 h.
      Under the standard assay conditions, interference from acid-labile phosphate as
      in the case of Na+,K+ ATPase was at the minimum. The applicability of the method
      for assay of microsomal Na+,K+ ATPase and glucose-6-phosphatase was checked in
      microassays (final volume 0.1 ml) in comparison to the conventional procedures
      which use 3-4 times higher volumes. Likewise the applicability of the method for
      phospholipid analysis was compared with that of the conventional Bartlett method.
      Under both test systems the results obtained by the micromethod were identical to
      those obtained by the conventional methods. In general the method, which rapidly
      produces quantitatively molybdenum blue color, not only is rapid economical, and
      convenient but also has wide applicability.

PMID- 14656524
TI  - Quantification of uridine 5'-diphosphate (UDP)-glucose by high-performance liquid
      chromatography and its application to a nonradioactive assay for nucleoside
      diphosphate kinase using UDP-glucose pyrophosphorylase as a coupling enzyme.
AB  - We describe a method for the detection and quantification of nucleoside
      diphosphate kinase (NDPK). NDPK catalyzes the transfer of the gamma-phosphate of
      cytidine 5'-triphosphate on uridine 5'-diphosphate (UDP) to produce uridine 5'
      triphosphate (UTP). The method uses a nonradioactive coupled enzyme assay in
      which UTP produced by NDPK is utilized by UDP-glucose pyrophosphorylase. This
      latter enzyme synthesizes UDP-glucose and inorganic phosphate in the presence of
      glucose 1-phosphate. UDP-glucose is detected at 260 nm after separation of the
      reaction mixture by high-performance liquid chromatography (HPLC) on a strong
      anion-exchange column. The assay is reliable, specific, and linear with respect
      to time and enzyme amount. Using 15 min incubation time, the method allows
      detection of NDPK activity below 10 pmol/min. It can be used to analyze kinetic
      behavior and to quantify NDPK from a wide variety of animal, microbial, and plant
      sources. It also provides an alternative to radiometric assays and an improvement
      on pyruvate kinase-linked spectrophotometric assays, which can be hampered by
      pigments present in crude extracts. Furthermore, we show that the HPLC method
      developed here can be directly used to assay enzymes for which UDP-glucose is a
      product.

PMID- 14656525
TI  - Application of biofluid 1H nuclear magnetic resonance-based metabonomic
      techniques for the analysis of the biochemical effects of dietary isoflavones on
      human plasma profile.
AB  - This study describes the first metabonomic approach to determining biochemical
      modifications following dietary intervention in humans. Significant interest in
      the mechanisms of action of soy isoflavones has predominantly stemmed from in
      vitro experiments but to date the availability of analytical tools for studying
      the mechanisms of action in vivo have been limited. Here a metabonomic approach
      based on chemometric analysis of 1H nuclear magnetic resonance spectra of blood
      plasma has been used to investigate metabolic changes following dietary
      intervention with soy isoflavones in healthy premenopausal women under controlled
      environmental conditions. Clear differences in the plasma lipoprotein, amino
      acid, and carbohydrate profiles were observed following soy intervention,
      suggesting a soy-induced alteration in energy metabolism.

PMID- 14656526
TI  - A selective 19F nuclear magnetic resonance spectroscopic method for the assay of
      the neuroleptic drug cis(Z)-flupentixol in human serum.
AB  - This investigation was carried out to evaluate 19F nuclear magnetic resonance as
      an analytical tool for the measurement of the cis(Z) and trans(E) stereoisomers
      of the antipsychotic drug flupentixol in human serum. The method is based on the
      integration of appropriate signals of both analytes and an internal standard. The
      proposed method was applied to the analysis of real samples without any
      interference, manipulation of large samples, and lengthy instrument time.
      Experimental parameters were selected to optimize accuracy, precision, and
      analysis time. The calibration curves in human serum matrix were linear for
      cis(Z)- and trans(E)-flupentixol over the ranges 4.0-50.0 and 2.6-25.0 microg/mL,
      respectively, with respective minimum detectable limits (S/N=3) of 1.67 and 1.72
      microg/mL. The method was validated through spike and recovery for the two
      isomers of flupentixol from a human serum matrix.

PMID- 14656527
TI  - Multi-point estimation of total energy expenditure: a comparison between zinc
      reduction and platinum-equilibration methodologies.
AB  - Reducing water to hydrogen gas by zinc or uranium metal for determining D/H ratio
      is both tedious and time consuming. This has forced most energy metabolism
      investigators to use the "two-point" technique instead of the "Multi-point"
      technique for estimating total energy expenditure (TEE). Recently, we purchased a
      new platinum (Pt)-equilibration system that significantly reduces both time and
      labor required for D/H ratio determination. In this study, we compared TEE
      obtained from nine overweight but healthy subjects, estimated using the
      traditional Zn-reduction method to that obtained from the new Pt-equilibration
      system. Rate constants, pool spaces, and CO2 production rates obtained from use
      of the two methodologies were not significantly different. Correlation analysis
      demonstrated that TEEs estimated using the two methods were significantly
      correlated (r=0.925, p=0.0001). Sample equilibration time was reduced by 66%
      compared to those of similar methods. The data demonstrated that the Zn-reduction
      method could be replaced by the Pt-equilibration method when TEE was estimated
      using the "Multi-Point" technique. Furthermore, D equilibration time was
      significantly reduced.

PMID- 14656528
TI  - Separation and recovery of DNA fragments by electrophoresis through a
      thermoreversible hydrogel composed of poly(ethylene oxide) and poly(propylene
      oxide).
AB  - We have synthesized and characterized a thermoreversible hydrogel of multiplied
      block copolymers, composed of poly(ethylene oxide) and poly(propylene oxide), for
      DNA electrophoresis. The aqueous solution of block copolymers turned into a
      hydrogel upon heating at temperatures above 10-11 degrees C, whereas it reverted
      into a solution upon cooling. Linear double-stranded DNA molecules migrated
      through the gel matrices at a rate that was inversely proportional to the
      logarithm of the DNA length. The hydrogel is most effective for separating DNA
      fragments in the 10- to 2000-bp range. The resolving range lay in-between the
      effective ranges of polyacrylamide and agarose gel electrophoreses of DNA. The
      gel slices containing DNA fragments were liquefied by cooling on ice, and the DNA
      was precipitated with ethanol. No contaminants that inhibit enzymatic reactions
      were found in the DNA recovered from the hydrogel. Plasmid DNA recovered from the
      hydrogel was recircularized with T4 DNA ligase and yielded highly efficient
      Escherichia coli transformation. Therefore, thermoreversible gel electrophoresis
      will be a useful method for DNA separation and isolation in recombinant DNA
      technology.

PMID- 14656529
TI  - Development of a fluorescence polarization assay to screen for inhibitors of the
      FtsZ/ZipA interaction.
AB  - A fluorescence polarization competition assay has been developed to screen for
      inhibitors of the Escherichia coli FtsZ/ZipA protein-protein interaction. A
      previously published X-ray costructure demonstrated that a 17-amino-acid peptide,
      corresponding to FtsZ C-terminal residues 367-383 (FtsZ(367-383)), interacts with
      the C-terminal FtsZ binding domain of ZipA (ZipA(185-328)). Phage display was
      employed to identify a unique but related peptide which when further modified and
      labeled was shown to have a higher affinity to ZipA(185-328) than the FtsZ(367
      383) peptide and binds to the same site. This peptide had a six fold increase in
      fluorescence polarization upon binding to ZipA(185-328) compared to a two fold
      increase for the FtsZ(367-383) fluorophore. As a result, assay parameters using
      the phage display peptide were further optimized and adapted for the high
      throughput screen. A high-throughput screen of 250,000 compounds identified 29
      hits with inhibition equal to or greater than 30% at 50 microg/ml. An X-ray
      costructure of a promising small molecule in this library complexed with ZipA(185
      328) (KI=12 microM) revealed that the compound binds to the same hydrophobic
      pocket as the FtsZ(367-383) peptide.

PMID- 14656530
TI  - A strategy for identification and quantification of detergents frequently used in
      the purification of membrane proteins.
AB  - A methodology that enables the identification and quantification of detergents
      frequently used in the purification of membrane proteins has been developed. The
      procedure consists of detergent separation via thin-layer chromatography,
      followed by visualization with iodine vapor staining and subsequent
      quantification with laser densitometry. We demonstrate that a panel of detergents
      that are frequently used to purify membrane proteins displays distinctive
      mobilities in a solvent system consisting of chloroform:methanol:ammonium
      hydroxide (63:35:5), thereby permitting their separation and identification. In
      addition, we establish with both the nonionic detergent dodecylmaltoside and the
      anionic detergent sarkosyl that a linear relationship between detergent quantity
      and optical density is obtained over a wide range of detergent levels.
      Furthermore, we demonstrate the accuracy and precision of the assay. Moreover, a
      strategy for determining the intrinsic iodine-staining capacity of a membrane
      protein following the removal of associated detergent is presented. Finally, we
      show the utility of this protocol in measuring detergent concentration following
      detergent exchange via gel filtration chromatography. The efficacy of this
      approach for characterizing the detergent present in purified membrane protein
      preparations prior to conducting crystallization trials is discussed.

PMID- 14656531
TI  - An enzyme-coupled assay for glyoxylic acid.
AB  - Herein, we present a new enzyme-linked spectrophotometric assay for glyoxylate
      that detects glyoxylate via the formation of an intensely colored formazan. This
      glyoxylate-specific assay is reliant upon the enzymatic conversion of glyoxylate
      to oxaloacetate coupled to the reduction of oxidized nicotinamide adenine
      dinucleotide to reduced nicotinamide adenine dinucleotide (NADH). The NADH
      dependent reduction of a tetrazolium to the formazan enables the measurement of
      nanomole quantities of glyoxylate in an assay that is amenable to high-throughput
      screening methods. Assay validation was accomplished using two methods for
      glyoxylate generation, the base-catalyzed N-dealkylation of alpha
      hydroxyhippurate to benzamide and glyoxylate and the oxidative cleavage of the
      glycyl Calpha-N bond in N-benzoylglycine (hippurate) by peptidylglycine alpha
      amidating monooxygenase to again yield benzamide and glyoxylate. For both
      reactions, analysis of benzamide produced by reverse-phase high-performance
      liquid chromatography compared with glyoxylate measured using our glyoxylate
      assay showed a 1:1 molar ratio of benzamide to glyoxylate. These results indicate
      that the enzyme-linked spectrophotometric assay can quantitatively measure
      submicromole quantities of glyoxylate.

PMID- 14656532
TI  - A simplified equation allowing the determination of kinetic constants of
      "invisible" substrates.

PMID- 14656533
TI  - Quantification of cyclic adenosine 5'-monophosphate in micromanipulated cells.

PMID- 14656534
TI  - Agarose gel size fractionation of RNA for the cloning of full-length cDNAs.

PMID- 14656537
TI  - Maedi-Visna virus infection in sheep. History and present knowledge.
AB  - Briefly the history of maedi-visna and the major clinical symptoms are described.
      Examples are presented to demonstrate that the genetic composition of a breed
      determines whether or not sheep become sick after an infection with maedi-visna
      virus (mvv) or develop solely specific antibodies. The major pathway of
      transmission is not colostrum and milk, but a cell containing increased nasal
      discharge in cases of respiratory distress. The role of the environment and
      prophylactic measures against parasites is stressed, because even sheep of highly
      susceptible breeds can survive an infection under optimal conditions. The virus
      and subsequently the disease simply die out. The cooperation between clinicians
      and laboratories is necessary.

PMID- 14656538
TI  - Respiratory chlamydial infection based on experimental aerosol challenge of pigs
      with Chlamydia suis.
AB  - An experimental study of aerogeneous challenge in pigs was conducted in order to
      reveal characteristic features of porcine respiratory chlamydiosis. Eight
      conventionally raised pigs were exposed to a pathogenic strain of Chlamydia (C.)
      suis, four controls were mock infected. Besides pathological changes, the acute
      phase and humoral immune responses, as well as the dissemination and transmission
      of the challenge strain was monitored in the course of infection. The data from
      clinical investigations, LPS-binding protein assay, antibody ELISAs, confocal
      laser scanning and light microscopy, immunohistochemical staining and PCR
      provided extensive evidence of the pathogenic potential of C. suis for the
      porcine respiratory system. This model appears suitable for further
      pathophysiological and immunological investigations of chlamydial respiratory
      infections and can also be recommended for studies of Chlamydia-associated
      infections of the human lung.

PMID- 14656539
TI  - Experimental infection of goats at different stages of pregnancy with caprine
      herpesvirus 1.
AB  - Three goats from a group of five caprine herpesvirus 1 (CpHV.1) seronegative
      pregnant goats were inoculated intranasally with a virulent BA.1 strain of
      CpHV.1. Goat n.1 was infected on day 45 of pregnancy, goat n.2 on day 92 and goat
      n.3 on day 127. Each of the three goats produced a single foetus 10-60 days after
      infection. Foetus n.1 was never found and so it could not be examined for
      virological findings. Goat n.2 delivered at term of gestation and CpHV.1 was
      detected by PCR and isolated from most of the foetal organs. Foetus n.3 was
      partially autolysed and the virus was only detected by PCR but not isolated from
      foetal organs. The results confirm the damaging effect of CpHV.1 infection on
      pregnancy, the difficulty in diagnosing the CpHV.1 induced abortion, and the
      importance developing appropriate prophylactic programmes.

PMID- 14656540
TI  - Characterisation of and immunity to the aerobic bacteria found in the pouch of
      the brushtail possum Trichosurus vulpecula.
AB  - The bacterial composition of the brustail possum (Trichosurus vulpecula) pouch
      was characterized throughout the reproductive cycle using brushtails from an
      Australian captive breeding colony (45 swabs) and a wild population in New
      Zealand (26 swabs). Gram-positive coccal species predominate throughout the
      reproductive cycle. Enteric Gram-negative rods, particularly Escherichia coli,
      were most prevalent when a pouch young was present and was most likely the result
      of faecal contamination from the pouch young. As culturing is only able to detect
      a proportion of bacteria present in a particular environment, molecular 16S rDNA
      sequencing was carried out on DNA extracted from a pouch wash of a female
      carrying a pouch young to gain a more accurate assessment of the pouch
      microflora. This approach identified approximately five times the number of
      bacterial species when compared to culture results. The majority detected were
      Gram negative rods or most closely related to Gram-negative rods species.
      Brushtails are immunologically immature at birth yet survive in a pouch colonised
      with potentially pathogenic bacteria. A haemagglutination assay was used to
      determine whether antibodies to a frequently isolated bacterium (Klebsiella
      pneumoniae) were transferred via milk from mother to pouch young. IgG antibodies
      were detected in maternal serum, milk and pouch young serum. In young over 70
      days, antibody titres were significantly higher than those found in maternal
      serum, suggesting that the young is capable of producing adult type antibodies to
      pouch bacteria at this time.

PMID- 14656541
TI  - Production of virus-specific antiserum corresponding to sequences in the lactate
      dehydrogenase-elevating virus (LDV) ORF6 protein.
AB  - The elucidation of the antigenic structure of the envelope proteins of
      Arteriviridae which includes lactate dehydrogenase-elevating virus (LDV) will
      provide further understanding of a mechanism of strict host cell specificity. To
      analyze the linkage between LDV envelope proteins, M/VP-2 and VP-3, which may
      play an important role in viral infectivity, we generated specific antibody
      against M/VP-2 that has not been reported in previous studies. A synthetic
      polypeptide corresponding to the C-terminal region of LDV strain C (LDV-C) ORF6,
      which encodes M/VP-2, was chemically synthesized and coupled to keyhole limpet
      hemocyanin (KLH). The peptide was immunogenic in rabbits and induced antibody
      specific for viral protein. Western blotting and immunofluorescence analysis of
      virion M/VP-2 in infected macrophages showed that the antibody was able to react
      specifically with authentic virion protein. The immunoreactive antibody against
      LDV M/VP-2 described in this study will be useful for further studies of the
      specific roles of the envelope proteins in arterivirus assembly and infectivity.

PMID- 14656542
TI  - Cytotoxic T lymphocyte activity and cytokine expression in calves vaccinated with
      formalin-inactivated bovine respiratory syncytial virus prior to challenge.
AB  - The development of effective, safe vaccines for human and bovine respiratory
      syncytial virus (RSV) has been problematic. Inactivated RSV vaccines are of
      variable efficacy; poor efficacy may be related to induction of ineffective cell
      mediated immunity (CMI). To characterize CMI in calves vaccinated with formalin
      inactivated (FI) BRSV, 11 calves were vaccinated twice with FI-BRSV (n=5) or mock
      vaccine (n=6) at a 2 week interval and challenged 1 month later. Prior to
      challenge a cannula was placed in the efferent lymphatic of the caudal
      mediastinal lymph node of each calf; lymph derived lymphocytes (LDL) were
      collected for analysis of CMI. Cytotoxic T lymphocyte (CTL) activity by LDL
      and/or peripheral blood mononuclear cells (PBMC) was measured by 51Cr release on
      days 5, 7, 9, and 10 post-challenge. Messenger RNA for interferon gamma (IFN
      gamma), interleukin 2 (IL-2) and IL-4 was measured on days 0-10 by
      semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA
      of LDL. BRSV-specific IFN-gamma production by PBMC was measured on days 0 and 10
      by ELISA. Clinical signs and postmortem changes following challenge were
      evaluated. There was no difference between groups in clinical signs, postmortem
      changes, CTL activity, cytokine message expression, or IFN-gamma production. For
      both groups, percentage lysis by CTL peaked on days 7-10 and ranged from 11 to
      25%. Failure of vaccination to prevent disease following challenge was likely
      associated with failure to prime for improved CMI responses.

PMID- 14656544
TI  - Drugs of abuse and the elicitation of human aggressive behavior.
AB  - The drug-violence relationship exists for several reasons, some direct (drugs
      pharmacologically inducing violence) and some indirect (violence occurring in
      order to attain drugs). Moreover, the nature of that relationship is often
      complex, with intoxication, neurotoxic, and withdrawal effects often being
      confused and/or confounded. This paper reviews the existing literature regarding
      the extent to which various drugs of abuse may be directly associated with
      heightened interpersonal violence. Alcohol is clearly the drug with the most
      evidence to support a direct intoxication-violence relationship. The literatures
      concerning benzodiazepines, opiates, psychostimulants, and phencyclidine (PCP)
      are idiosyncratic but suggest that personality factors may be as (or more)
      important than pharmacological ones. Cannabis reduces likelihood of violence
      during intoxication, but mounting evidence associates withdrawal with
      aggressivity. The literature on the relationship between steroids and aggression
      is largely confounded, and between 3,4-methylenedioxymethamphetamine (MDMA) and
      aggression insufficient to draw any reasonable conclusions. Conclusions and
      policy implications are briefly discussed.

PMID- 14656545
TI  - Intimate partner violence and substance use: a longitudinal day-to-day
      examination.
AB  - The likelihood of male-to-female physical aggression on days of male partners'
      substance use, during a 15-month period, was examined. Participants were from
      married or cohabiting partner violent men entering a drug abuse treatment program
      (N=149). Compared to days of no drug or alcohol use, the likelihood of male-to
      female physical aggression was significantly higher on days of substance use,
      after controlling for male partners' antisocial personality (ASP) disorder and
      couples' global relationship distress. Of the psychoactive substances examined,
      the use of alcohol and cocaine was associated with significant increases in the
      daily likelihood of male-to-female physical aggression; cannabis and opiates were
      not significantly associated with an increased likelihood of male partner
      violence.

PMID- 14656546
TI  - The association between alcohol use and intimate partner violence: linear effect,
      threshold effect, or both?
AB  - The present study examined whether the association between alcohol and male-to
      female intimate partner violence (IPV) is most meaningfully described as a linear
      relationship, a threshold effect, or both. Men in two nationally representative
      samples, the National Family Violence Survey (NFVS) and the National Survey of
      Families and Households (NSFH), were divided into similar drinking groups based
      on quantity and frequency of alcohol consumption. Analyses of the association
      between IPV and drinking category revealed that although linear associations
      between drinking classification and IPV were significant in both samples, the
      associated effect sizes were very small. Further, only heavy drinkers and binge
      drinkers were major contributors to the significant chi-squares. Overall, the
      results revealed both linear and threshold effects, and suggest that distinctions
      among drinking patterns may be more important than incremental increases in
      quantity or frequency in conceptualizing alcohol as a risk factor for IPV.

PMID- 14656547
TI  - Perpetration of partner violence: effects of cocaine and alcohol dependence and
      posttraumatic stress disorder.
AB  - The present study examined the effects of substance dependence and posttraumatic
      stress disorder (PTSD) on perpetration of partner violence. Participants were 72
      men and 124 women diagnosed with and/or without PTSD and cocaine or alcohol
      dependence. Participants were interviewed with the Structured Clinical Interview
      for the DSM-IV (SCID-IV) and completed the Conflict Tactics Scale-2 (CTS-2).
      Analyses indicated that participants with comorbid cocaine dependence and PTSD
      reported the highest frequency of partner violence relative to all other groups.
      Main effects were also detected for drug dependence and PTSD. Results suggest
      that substance dependence and PTSD alone are associated with increased violence
      in couples, and most importantly, the presence of PTSD serves to further
      potentiate the perpetration of partner violence among cocaine-dependent
      individuals.

PMID- 14656548
TI  - Relationship aggression and substance use among women court-referred to domestic
      violence intervention programs.
AB  - Although there is extensive theoretical and empirical evidence linking men's
      alcohol abuse and marital violence, no previous studies have assessed the
      substance use characteristics of women arrested for domestic violence. We
      recruited 35 women who were arrested for domestic violence and court-referred to
      batterer intervention programs. We administered multiple measures of substance
      use and abuse and assessed the women's marital aggression, marital satisfaction,
      depressive symptomatology, use of general violence, and their relationship
      partners' substance use. We also divided the sample into groups of hazardous
      drinkers (HD) and nonhazardous drinkers (NHD). Across the entire sample, almost
      half of the women were classified as HD. Over one-quarter of the women reported
      symptoms consistent with an alcohol abuse or dependence diagnosis, and
      approximately one-quarter of the sample reported symptoms consistent with a drug
      related diagnosis. Over one-half of the total sample reported that their
      relationship partners were HD. Relative to the NHD group, the HD group scored
      higher on measures of drug problems, relationship aggression, general violence,
      and marital dissatisfaction. The results of the study suggest that substance use
      and abuse should routinely be assessed as part of batterer interventions and that
      batterer programs would be improved by offering adjunct or integrated alcohol
      treatment.

PMID- 14656549
TI  - PTSD symptom severity as a predictor of cue-elicited drug craving in victims of
      violent crime.
AB  - This study examined posttraumatic stress disorder (PTSD) symptom severity as a
      predictor of cue-elicited craving among alcohol- and cocaine-dependent
      individuals with a history of at least one physical and/or sexual assault.
      Approximately half of the sample had current PTSD. Severity of PTSD symptoms was
      measured via the Impact of Events Scale-Revised (IES-R) total severity score.
      Subjects listened to four trials of a brief narrative imagery script followed by
      the presentation of an in vivo cue. The script presentation consisted of a
      description of either the subject's worst traumatic event or a neutral scene. The
      in vivo cues consisted of the presentation of either the subject's preferred drug
      or neutral cues. Craving was measured in response to both the script and in vivo
      cues. Results indicated a high degree of correlation between self-report craving
      and (a) PTSD symptom severity, (b) type of substance use disorder (SUD) [alcohol
      dependence (AD) vs. cocaine dependence (CD)], and (c) sex and race of
      participant. A series of stepwise multiple regressions indicated that PTSD
      severity was significantly predictive of trauma cue-elicited craving and drug cue
      elicited craving. The results are discussed in the context of current research,
      theory, and clinical practice.

PMID- 14656550
TI  - The effects of trauma history, gender, and race on alcohol use and posttraumatic
      stress symptoms in a college student sample.
AB  - The present study examined the extent to which different types of traumatic
      experiences interact with sex and race to effect alcohol use, posttraumatic
      stress symptomatology, and general psychological distress among a college student
      sample. Approximately 600 participants completed measures that assessed for a
      childhood sexual abuse (CSA) history, alcohol consumption, posttraumatic stress
      symptoms, and overall psychological functioning. Findings indicated that
      participants with a history of CSA reported greater psychological distress and
      posttraumatic stress symptoms compared to participants with a trauma history
      other than CSA and participants with no trauma history. Despite group differences
      in psychological distress and posttraumatic stress symptoms, no differences in
      alcohol use were detected across groups. Gender appeared to affect posttraumatic
      stress symptoms as a function of group. The implications of the results are
      discussed.

PMID- 14656551
TI  - Women's substance use and experiences of intimate partner violence: a
      longitudinal investigation among a community sample.
AB  - Although cross-sectional studies reveal an association between women's substance
      use and experiencing physical violence from one's intimate partner, the temporal
      ordering of these variables is not clearly established. The current study
      involved longitudinal examination of the association of women's substance use
      with subsequent experiences of intimate partner violence as well as the
      association between women's experiences of intimate partner violence and their
      subsequent substance use. Women ages 18-30 who were in heterosexual relationships
      (n=724) were recruited through random digit dialing in the Buffalo, NY, area.
      Within ongoing relationships, women's use of hard drugs was associated with
      increased odds of experiencing intimate partner violence over the next 12 months.
      Both marijuana and hard drug use were associated with increased likelihood of
      experiencing violence in new relationships. Women's heavy episodic drinking did
      not predict subsequent experiences of partner violence in ongoing or new
      relationships. Experiences of intimate partner violence had a significant effect
      on subsequent relationship satisfaction, which was modestly associated with
      subsequent heavy episodic drinking but not with subsequent drug use.

PMID- 14656552
TI  - Smoking patterns, symptoms of PTSD and depression: preliminary findings from a
      sample of severely battered women.
AB  - Intimate partner violence (IPV) is a public health problem that significantly
      impacts the physical and emotional well-being of women. In addition to the health
      risk associated with violence exposure, female victims of IPV are at increased
      risk of engaging in damaging health behaviors, including cigarette smoking. The
      present study examined patterns of cigarette smoking, using the Fagerstrom Test
      for Nicotine Dependence (FTND), and explored its association with
      sociodemographic factors, characteristics of physical, psychological, and sexual
      forms of IPV, symptoms of posttraumatic stress disorder (PTSD), and depression
      within 62 female victims of severe battering. Fifty-eight percent of the total
      sample reported that they were current smokers. Within the group of current
      smokers, women who evidenced greater symptoms of nicotine-related physical
      dependence (NRPD) were more likely to be unemployed, have less education,
      experience more recent violence, more severe IPV-related sexual coercion, more
      IPV-related dominance/isolation, and more severe symptoms of PTSD and depression.
      In addition, greater symptoms of NRPD were significantly and positively
      associated with PTSD clusters of reexperiencing and arousal. Implications for
      these preliminary findings were discussed and directions for future research were
      detailed.

PMID- 14656553
TI  - Drinking, personality, and bar environmental characteristics as predictors of
      involvement in barroom aggression.
AB  - Theoretical approaches to alcohol and violence have emphasized three interrelated
      domains of influence: the situational context, aggression-facilitating
      characteristics of individuals, and the impact of alcohol consumption. We
      examined these three domains as predictors of experiencing violence in the
      barroom setting. Participants were recruited through one of two phone surveys or
      through newspaper advertisements and classified into one of three groups:
      Experienced Bar Violence (EBV), Observed Bar Violence (OBV), and No Bar Violence
      (NBV). They completed questionnaires assessing individual difference and alcohol
      use variables, and an interview that assessed characteristics of their usual bar.
      The results suggested that individual difference and alcohol variables
      distinguished men in the EBV group from men in the OBV and NBV groups. However,
      women in the EBV group were distinguished from women in the NBV group by the
      characteristics of their usual bar and by the alcohol variables, but were
      distinguished from the OBV group only in terms of individual difference
      variables. The implications of these findings with respect to the influence of
      alcohol on barroom violence are discussed.

PMID- 14656554
TI  - An acute post-rape intervention to prevent substance use and abuse.
AB  - The trauma of rape is routinely associated with extreme acute distress. Such peri
      event anxiety increases risk of developing psychopathology and substance use or
      abuse post-rape, with the degree of initial distress positively predicting future
      problems. Unfortunately, the nature of post-rape forensic evidence collection
      procedures may exacerbate initial distress, thereby potentiating post-rape
      negative emotional sequelae. Consequently, substance use may increase in an
      effort to ameliorate this distress. To address this, a two-part video
      intervention was developed for use in acute post-rape time frames to (a) minimize
      anxiety during forensic rape examinations, thereby reducing risk of future
      emotional problems, and (b) prevent increased post-rape substance use and abuse.
      Pilot study data with 124 rape victims indicated that the low-cost, easily
      administered intervention was effective in reducing risk of marijuana abuse at 6
      weeks. Nonstatistically significant trends also were evident for reduced
      marijuana use. Trends were also noted in favor of the intervention in the
      subgroup of women who were actively using substances pre-rape (among pre-rape
      alcohol users, 28% viewers vs. 43% nonviewers met criteria for post-rape alcohol
      abuse; among pre-rape marijuana users, the rates of post-marijuana use were 17%
      vs. 43%).

PMID- 14656555
TI  - Demographic and social adjustment characteristics of patients with comorbid
      posttraumatic stress disorder and alcohol dependence: potential pitfalls to PTSD
      treatment.
AB  - The present study examined the demographic and social adjustment characteristics
      of a sample seeking treatment for comorbid posttraumatic stress disorder (PTSD)
      and alcohol dependence (AD). Using descriptive statistics, we compared the
      characteristics of this group to those of a sample seeking treatment for PTSD
      alone and to another sample seeking treatment for AD alone. Results indicated
      that compared to the PTSD alone and AD alone samples, a greater percentage of the
      comorbid sample was unemployed, with low income and living without the support of
      a spouse or intimate partner. Further, participants in the comorbid sample were
      less likely than those in the PTSD alone sample to have received more than a high
      school education, though the comorbid and AD samples were comparable on education
      level. These results are discussed with attention to how poor social adjustment
      may place comorbid AD-PTSD patients at greater risk for premature termination of
      therapy, particularly when that treatment is focused on alleviating PTSD
      symptoms. Suggestions are made to enhance retention of these difficult patients
      in treatment programs.

PMID- 14656556
TI  - Multisystemic therapy: a treatment for violent substance-abusing and substance
      dependent juvenile offenders.
AB  - Adolescent violence and substance abuse result in substantial personal and
      societal cost. Many treatments fail to produce favorable outcome in terms of both
      violence and substance abuse with adolescents because they fail to
      comprehensively address etiological and maintaining factors. This article
      describes multisystemic therapy (MST), a family- and community-based treatment
      that has produced favorable outcomes with violent substance-abusing or -dependent
      adolescents in both realms. The clinical basis for the success of MST and studies
      supporting its effectiveness with violent and substance-abusing adolescents are
      presented.

PMID- 14656557
TI  - Effect of the loss of auditory feedback on segmental parameters of vowels of
      postlingually deafened speakers.
AB  - OBJECTIVE: The most obvious and best documented changes in speech of
      postlingually deafened speakers are the rate, fundamental frequency, and volume
      (energy). These changes are due to the lack of auditory feedback. But auditory
      feedback affects not only the suprasegmental parameters of speech. The aim of
      this study was to determine the change at the segmental level of speech in terms
      of vowel formants. METHODS: Twenty-three postlingually deafened and 18 normally
      hearing speakers were recorded reading a German text. The frequencies of the
      first and second formants and the vowel spaces of selected vowels in word-in
      context condition were compared. RESULTS: All first formant frequencies (F1) of
      the postlingually deafened speakers were significantly different from those of
      the normally hearing people. The values of F1 were higher for the vowels /e/
      (418+/-61 Hz compared with 359+/-52 Hz, P=0.006) and /o/ (459+/-58 compared with
      390+/-45 Hz, P=0.0003) and lower for /a/ (765+/-115 Hz compared with 851+/-146
      Hz, P=0.038). The second formant frequency (F2) only showed a significant
      increase for the vowel/e/(2016+/-347 Hz compared with 2279+/-250 Hz, P=0.012).
      The postlingually deafened people were divided into two subgroups according to
      duration of deafness (shorter/longer than 10 years of deafness). There was no
      significant difference in formant changes between the two groups. CONCLUSION: Our
      report demonstrated an effect of auditory feedback also on segmental features of
      speech of postlingually deafened people.

PMID- 14656558
TI  - Eye movements evoked by the selective stimulation of the utricular nerve in cats.
AB  - OBJECTIVE: Eye movements evoked by otolith organ are not well-investigated
      compare with canal related eye movements due to the technical difficulties. We
      try to solve this problem by means of our methods. METHODS: Eye movements evoked
      by selective utricular (UT) nerve stimulation were investigated using both
      electrooculography (EOG) and video recording in decerebrated cats in the presence
      or absence of anesthesia. Electrical stimulation was applied to the UT nerve
      through implanted acupuncture needles. RESULTS: In the absence of anesthesia and
      with stimulus intensities less than 2.6+/-0.7 x N(1)T, we found ipsilaterally
      directed horizontal eye movements in both eyes in one cat, abduction in the
      ipsilateral eye in two cats, and adduction in the contralateral eye in another
      cat. Other types of eye movements (e.g., supraduction or diagonal eye movements)
      were observed in both eyes of cats in the absence of anesthesia at a stimulus
      intensity of 12.2+/-7.6 x N(1)T, an intensity in which current spread to the
      adjacent nerve could not be ruled out. In the presence of anesthesia, UT nerve
      stimulation alone failed to evoke horizontal eye movements, but with an intensity
      13.8+/-6.4 x N(1)T, supraduction or diagonal eye movements were evoked. UT nerve
      stimulation at 2-3 x N(1)T facilitated horizontal eye movements induced by
      ipsilateral abducens (AB) nucleus stimulation or contralateral horizontal canal
      nerve stimulation. CONCLUSION: This is the first report to our knowledge in which
      UT nerve-evoked horizontal eye movements are documented. These results confirm
      the known monosynaptic and disynaptic anatomical connections from utricular
      primary afferents to the ipsilateral AB nucleus neurons.

PMID- 14656559
TI  - Electrocochleographic findings in cases of autoimmune disease with sensorineural
      deafness.
AB  - OBJECTIVES: To present electrocochleographic findings in patients with autoimmune
      disease (AD) with sensorineural deafness (ADSD), and to discuss the etiologies of
      sensorineural hearing loss (SNHL) in cases of ADSD. METHODS: Study design is a
      retrospective review of electrocochleographic results of 26 patients with ADSD.
      To evaluate the electrocochleographic results, average SP/AP ratios were compared
      between ADSD and normal subjects. In the ADSD group, audiologic pattern,
      fluctuations in hearing and results of the glycerol test were also reviewed.
      Electrocochleography (ECoG) was recorded using the extratympanic method, and the
      SP to AP ratio (SP/AP ratio) was analyzed. RESULTS: The mean of average SP/AP
      ratios in the ADSD groups (0.46) was significantly higher than that in normal
      subjects (0.27). Further, 17 of 29 affected ears in patients with ADSD showed
      fluctuating hearing loss. Eighteen ears showed low tone loss (rising and peak
      audiologic patterns). Only 5 of 26 ears (19.2%) showed positive results on
      glycerol test. There was no correlation between glycerol test results and hearing
      fluctuation or between glycerol test results and the SP/AP ratio on chi(2)-test.
      There was no tendency between audiologic pattern and glycerol test results or
      between audiologic pattern and the SP/AP ratio. CONCLUSION: These results suggest
      the etiologies of SNHL in cases of ADSD remain unclear. However, some cases
      showed clinical findings similar to endolymphatic hydrops. We should bear in mind
      that clinical Meniere's syndrome involves ADSD. Further investigation is needed
      to resolve the etiology of SNHL of ADSD.

PMID- 14656560
TI  - Induction of apoptosis in the vestibule of guinea pigs after middle ear
      inoculation with lipopolysaccharide (LPS).
AB  - OBJECTIVE: During the process of apoptosis, double-stranded DNA is broken into
      single-stranded DNA (ssDNA) by the action of caspases and caspase activated
      deoxyribonuclease (CAD). We immunohistochemically examined the apoptotic changes
      induced by endotoxin in the vestibule of guinea pigs. METHODS: Lipopolysaccharide
      (LPS) (5 mg/ml, 0.2 ml), a bacterial endotoxin, was transtympanically injected
      into the middle ear. 48 h after injection of LPS, animals were sacrificed by
      intracardiac perfusion of fixative. The temporal bones were then removed and
      immunohistochemically stained for ssDNA, CAD and caspase 3. RESULTS: ssDNA was
      detected after 48 h in the dark cell area of the LPS group, not in the sensory
      epithelium. CAD was observed both in the dark cell area and the sensory
      epithelium. Caspase 3 was also detected both in the dark cell area and the
      sensory epithelium. CONCLUSION: Our findings suggest that apoptosis is involved
      in the dysfunction of the vestibule under inflammatory conditions.

PMID- 14656561
TI  - The effect of gravity on the stability of human eye orientation.
AB  - OBJECTIVE: The stabilization of both the horizontal (H) and vertical (V) eye
      movements during voluntary fixation is believed to depend upon the visual
      feedback system in the upright position. However, ocular stability in the tilted
      position has been less well investigated. Therefore, in the present study, we
      examined the gaze stability of healthy human subjects in the three dimensions in
      the tilted position using a video image analysis system (VIAS). METHODS: In 10
      healthy human subjects, the eye movements were recorded after fixating the eye on
      a target in an upright position and also in the tilted position. The standard
      deviations of the eye movements in the three dimensions were calculated to
      evaluate the stability of the movements. RESULTS: In the tilted position, there
      were no significant changes in the horizontal and vertical eye movements as
      compared those in the upright position. However, the standard deviation of the
      torsional (T) segment was significantly larger in the tilted position, compared
      to that in the upright position. CONCLUSION: From these results, we speculate
      that, a combination of otolith and somatosensory inputs play a major role in
      maintaining the stability of eye movements.

PMID- 14656562
TI  - Auditory lexical-semantic processing impairments in aphasic patients reflected in
      event-related potentials (N400).
AB  - OBJECTIVE: Event-related potentials (ERPs) and response latencies were recorded
      from aphasic subjects with auditory language processing impairments and age
      matched normal controls, while performing a lexical-semantic evaluation task,
      aiming at clarifying whether ERPs could be a reliable measure for indicating
      language impairments in aphasic patients. METHODS: The stimuli were 50 pairs of
      spoken words (prime word-target word): 25 pairs, which were semantically and/or
      associatively related to each other, and 25 pairs which were not. The subjects
      pressed a switch in response to the presentation of target words semantically
      related to the prime words. The ERP component analyzed in this study was N400.
      RESULTS: With the performances, the response latencies were longer in the aphasic
      subjects than in the normal controls. With the ERPs, onset latencies of N400 were
      shifted behind in the aphasic patients compared to the normal controls. For the
      aphasic patients, there were correlations between the size of N400 and
      performances in auditory comprehension evaluated in the aphasia test. CONCLUSION:
      The conclusions drawn from the results are that not only response latencies in
      the lexical-semantic judgement task, but also N400 effects, may be a reliable
      clinical measure of the severity of even mild lexical-semantic impairments in
      aphasic patients.

PMID- 14656563
TI  - Acoustic rhinometric assessment of nasal obstruction after treatment with
      fluticasone propionate in patients with perennial rhinitis.
AB  - OBJECTIVE: To investigate the effect of fluticasone propionate (FP) on the
      symptom of nasal obstruction and to assess the correlation between the subjective
      visual analogue score (VAS) and the objective acoustic rhinometry (AR)
      measurements. METHODS: A prospective study of 45 consecutive patients, 30 males
      and 15 females with a mean age of 27 years (range: 16-59 years), with
      moderate/severe symptoms of perennial rhinitis who were treated by FP nasal spray
      for 4 weeks. AR and VAS were used to evaluate, compare and correlate the efficacy
      of FP nasal sprays. RESULTS: There was a significant improvement in the VAS post
      treatment (3.9) compared with pre-treatment (6.3). There was also a significant
      increase in the nasal volume (V) and minimum cross-sectional area (MCA) after
      intranasal FP. Good correlation between the total MCA and total V was noted.
      Subjective improvements in symptoms did not correlate well with objective
      measurements as the correlation between VAS and AR was poor. CONCLUSION: Our
      study provides subjective and objective evidence on the efficacy of intranasal FP
      in improving nasal obstruction in perennial rhinitis. AR also proved to be a
      useful instrument in monitoring the effectiveness of medical therapy for
      perennial rhinitis.

PMID- 14656564
TI  - Investigation of normal and malignant laryngeal tissue by autofluorescence
      imaging technique.
AB  - OBJECTIVE: During oncogenesis significant changes in tissue properties occur that
      result in alteration of fluorescence characteristics of the tissue. The
      differences in autofluorescence between normal and malignant tissues offer new
      possibilities in detecting epithelial pathological lesions. AIM: The aim of our
      study was to determine the usefulness of autofluorescence technique in diagnostic
      of laryngeal tumors. MATERIAL AND METHODS: Fluorescence in larynxes from 10
      laryngectomized cancer patients was induced by excitation light at 360-450 nm
      wavelength. As a light source, mercury lamp and laser (404 nm) were used. The CCD
      camera captured the fluorescent light emitted. Normal epithelium and cancer
      tissue were also analyzed on fluorescence microscopy. RESULTS: Laryngeal
      carcinoma tissues when excited with ultraviolet or blue light generate attenuated
      or absent autofluorescence in the green light band compare with normal epithelium
      where strong signal around 505 nm was detected. Average value of maximal
      autofluorescence intensities was 26.2V (range 18-35) and 4.4V (range 2-8) in
      healthy and cancerously changed mucosa respectively. Spectral analysis revealed
      that autofluorescence signal from unchanged mucosa (around 505 nm) was
      significantly higher compared to cancer tissue (P=0.005). CONCLUSIONS: It seems
      that autofluorescence imaging may be a supplementary tool in diagnosis of
      laryngeal tumors.

PMID- 14656565
TI  - Lethal post-tonsillectomy hemorrhage.
AB  - BACKGROUND: Post-tonsillectomy hemorrhage (PTH) seems to be a rare but
      unavoidable complication. Due to the frequency of performed tonsillectomies, it
      can be estimated that a certain amount may result in a lethal outcome. This study
      was undertaken to evaluate the clinical features of these rare cases. MATERIAL
      AND METHODS: Retrospective case series of five patients with lethal post
      tonsillectomy hemorrhage are reported after they had undergone tonsillectomy by
      four different surgeons. The relevant literature was reviewed. RESULTS: The
      youngest patient was 42 months and the oldest almost 13 years old. All patients
      were male. Three patients had left the hospital against surgeon's recommendation
      5 days following tonsillectomy. Preceding episodes of bleeding prior to the
      lethal bleeding occurred in two patients. Lethal PTH occurred in four patients
      within 5-9 days, the latest bleeding 39 days after surgery. In the literature,
      lethal PTH was described for eight patients since 1958. The youngest patient was
      4 years, the oldest 18 years old (mean: 8.6 years; median: 6.5 years). In three
      patients, lethal PTH occurred on the day of surgery and the latest bleeding 54
      days after surgery. CONCLUSION: Due to the paucity of reports, little reliable
      information can be obtained from the literature. It remains unclear, whether or
      not this reflects the true incidence of this complication. The experience with
      the five reported cases suggests, that immediate surgical treatment may have
      avoided lethal outcome in most cases. Therefore, a close postoperative follow-up
      is advisable to detect any episode of bleeding as soon as possible which should
      be referred to a specialist. Certainly, the collected data do not suffice to
      establish general guidelines, indicating that further collection of cases is
      required to assess characteristics of lethal PTH.

PMID- 14656566
TI  - Foreign bodies in the aerodigestive tract in pediatric patients.
AB  - OBJECTIVE: To investigate pediatric foreign body cases in the aerodigestive
      tract, and to elucidate the characteristic problems in Japan. METHODS: A total of
      310 pediatric patients (age 15 or below), gathered from two medical university
      hospitals (University of Tokyo and Jichi Medical School), were included in this
      study. Data were collected by retrospective chart review and were statistically
      analyzed. RESULTS: Two-year-olds were the most common patients, and the range
      from age 1 to age 4 included 67.7% of all the patients. The most involved sites
      were the nose (39.4%) and the pharynx (38.4%), followed by the esophagus (12.9%)
      and the trachea-bronchi (6.5%). Fish bones and toys were the representative
      foreign bodies (30.7 and 13.6%, respectively). Other foreign bodies often
      encountered included coins, food, candy, peanuts and nuts, and batteries. The
      type of foreign body was closely related to the site in which foreign bodies were
      lodged: 77.3% of foreign bodies in the pharynx were fish bones, and toys were the
      most common impacted foreign body in the nose. In the esophagus, representative
      impacted foreign bodies were coins (35.7%), but disk-type battery ingestion has
      been increasing in recent years. Although most foreign bodies in the esophagus
      were safely removed, one case of a disk-type battery had a serious sequela. In
      the trachea-bronchi, peanuts, food, cotton, and coins were impacted. A rigid
      bronchoscope was basically used to remove foreign bodies, but in some cases, a
      fine flexible endoscope, with a channel for fiber forceps, was useful, because it
      could be inserted into narrow bronchi. Advance of a flexible endoscope will make
      it an excellent tool for diagnosis and management of the trachea-bronchial
      foreign body. CONCLUSIONS: Fish bones in the pharynx, which were closely related
      to Japanese eating habits, and toys in the nose, were the typical foreign bodies
      encountered in this study. In the esophagus, an increased incidence of disk-type
      battery ingestion has become a serious problem in recent years. Since prevention
      is the most essential way to manage foreign body cases, feedback from studies to
      public education should be encouraged.

PMID- 14656567
TI  - Anti-tumor effect of vitamin A and D on head and neck squamous cell carcinoma.
AB  - OBJECTIVES: Vitamin A and D(3) have a very strong differentiation induction
      effect. STUDY DESIGN: We examined the anti tumor effect on head and neck squamous
      cell carcinoma (HNSCC) by treatment with several vitamins having strong
      differentiation induction effects in vitro. METHODS: We used KB cell that an oral
      floor squamous cell carcinoma, vitamins as all-trans retinoic acid (ATRA), 4-[3,5
      bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), 1alpha,25(OH)(2)D(3)
      (calcitriol) and 22-oxa-1,25-(OH)(2)D(3) (OCT). We determined receptors of
      vitamin A and D(3) using RT-PCR. Furthermore, we investigated the proliferation
      of tumor cells in concentration dependency using [3H]TdR uptake method, apoptosis
      and apoptosis related factors using TUNEL method and real-time PCR, cell cycle
      changes using flow cytometry, changing of the sensitivity of using MTT method,
      cytokine production and the angiogenesis factor using ELISA, by treatment with
      these vitamins. RESULTS: The deficit of RAR-beta was found in the KB cell. Each
      vitamin suppressed the cell proliferation, induced apoptosis, and cell cycle
      arrest, upregulated sensitivity of the chemotherapeutics drugs and downregulated
      several angiogenesis factors and an apoptotic factor; survivin. CONCLUSIONS:
      These results support the idea that vitamin A, D(3) and their derivatives are
      useful for preventing and/or treating patients with HNSCC.

PMID- 14656568
TI  - The potential of a plastination specimen for temporal bone surgery.
AB  - OBJECTIVE: The benefits of plastination specimens in temporal bone surgery (TBS)
      were evaluated. METHODS: A formalin-preserved human temporal bone was drilled and
      dissected with the middle cranial fossa approach or the translabyrinthine (or
      transcochlear) approach. The specimen was thereafter subjected to silicon
      impregnation. RESULTS: The flexibility of the dura mater after plastination was
      maintained, and not only bony structures such as the auditory ossicles and
      semicircular canals but also soft tissues such as the facial nerve, internal
      carotid artery and the sinus attached to the dura mater were easily
      discriminated. CONCLUSION: The technique furnishes a persistently dry, odorless
      and durable specimen that allows handling and may serve as the most ideal
      specimen for anatomical learning of various approaches of TBS.

PMID- 14656569
TI  - Pleomorphic adenoma originated from the inferior nasal turbinate.
AB  - Although pleomorphic adenoma is the most common benign neoplasm of the salivary
      glands, it has also been reported to be present in the neck, ear, mediastinum,
      external nose and nasal cavity. Intranasal localization of this lesion is very
      rare and mainly originates from the nasal septum. From wherever the lesion
      originates, the main treatment modality should be surgical. We presented a very
      rare case of intranasal pleomorphic adenoma originated from the inferior nasal
      turbinate. Due to the expansile nature of the lesion, a midfacial degloving
      approach was preferred.

PMID- 14656570
TI  - Nevoid basal cell carcinoma syndrome: report of an aggressive case with ethmoid
      sinus invasion.
AB  - Nevoid basal cell carcinoma syndrome, also referred to as Gorlin-Goltz syndrome,
      is a rare autosomal dominant disorder characterized by multiple basal cell
      carcinomas, jaw cysts, palmar or plantar pits, ectopic calcification of the falx
      cerebri, and various skeletal developmental abnormalities. A minority of basal
      cell carcinomas demonstrate aggressive behavior and involve the craniofacial
      bones in nevoid basal cell carcinoma syndrome. A non-familial case of nevoid
      basal cell carcinoma syndrome with a basal cell carcinoma of the eyelid invading
      to the ethmoid sinus is reported.

PMID- 14656571
TI  - Schwannoma of the trachea; a new resection technique.
AB  - Tumors of the trachea are rare, especially schwannoma. We diagnosed a 27-year-old
      man with schwannoma of the trachea after he was admitted to our hospital with
      complaints of progressive dyspnea and wheezing. He was treated as having
      bronchial asthma initially, but his signs and symptoms did not improve with
      conventional therapy. Flexible fiberscopy revealed the presence of a submucosal
      tumor in the subglottic area. Tracheal tomography, computed tomography (CT) and
      magnetic resonance imaging (MRI) revealed the presence of a mass in the trachea
      that extended from the cricoid cartilage level to the second tracheal ring. After
      tracheostomy, we removed the tumor from a tracheostoma upwards to the larynx
      without a laryngofissure, using forceps and scissors usually used for
      laryngomicrosurgery and endoscopes usually used for sinus surgery. No
      complications developed during or after the procedure. To our knowledge, this is
      the first report of the removal of a tracheal schwannoma by this technique.

PMID- 14656572
TI  - Lump sensation in the throat caused by tumors in the preepiglottic space.
AB  - Lump sensation in the throat is a common symptom, which accounts for 4% of first
      patient visits to Otorhinolaryngologic clinics. The etiology includes
      abnormalities of the thyroid gland, cysts, tumors and chronic infections of the
      pharynx, larynx, esophagus and tongue base, gastroesophageal reflux and anxiety
      disorders. In this article we describe two rare cases of lump sensation caused by
      masses in the preepiglottic space and we stress the importance of thorough
      investigation to exclude any possible non functional causes.

PMID- 14656573
TI  - A case of idiopathic tracheal stenosis.
AB  - Idiopathic tracheal stenosis (ITS) is an extremely rare disease. We report the
      case of a 32-year-old woman with ITS. She had no history of previous surgery,
      endotracheal intubation, neck trauma, granulomatous disease, or any other severe
      respiratory tract infections. She presented with progressive dyspnea on effort
      and had been treated for bronchial asthma for 3 years. Chest radiography and
      laboratory examinations revealed no abnormalities. Bronchoscopy demonstrated
      almost circumferential tracheal stenosis extending for 10 mm from about 20 mm
      below the vocal cords. Luminal diameter was about 4 mm at the narrowest.
      Bronchoscopic biopsy revealed increased fibrous tissue and chronic inflammatory
      cell infiltration (nonspecific inflammatory tissue). These finding are compatible
      with idiopathic stenosis as reported by Grillo et al. After tracheostomy, the
      patient was treated by tracheal segmental resection (two rings) with end-to-end
      anastomosis of the cartilaginous trachea. Symptoms of tracheal stenosis were
      completely relieved and no recurrence has been observed as of 3 years
      postoperatively.

PMID- 14656574
TI  - Carcinosarcoma of the submandibular gland: an autopsy case.
AB  - Malignant mixed tumors of salivary glands are classified as three types:carcinoma
      arising in a pleomorphic adenoma, the most common; benign metastasizing
      pleomorphic adenoma; and carcinosarcoma (true malignant mixed tumor), which is
      very rare [Ann. Otol. Rhinol. Laryngol. (1982) 91 342]. In carcinoma, both
      epithelial and soft tissue elements are malignant. In the context of previous
      reports, we discuss a case of carcinosarcoma of the submandibular gland including
      the results of postmortem examination.

PMID- 14656575
TI  - Malignant vagal paraganglioma: report of a case treated with embolization and
      surgery.
AB  - Approximately 20 cases of malignant vagal paragangliomas (MVP)have been reported
      in English literature. Malignancy is based on the presence of metastases. A
      careful preoperative evaluation is necessary to detect multicentricity and/or
      significant production of catecholamines. A new case of MVP treated with
      embolization and surgery is presented and the literature discussed. It is
      concluded, that preoperative embolization followed by radical surgical resection
      is a rational treatment of patients with unilateral MVP.

PMID- 14656576
TI  - Multiple huge osteomas of the mandible causing disfigurement related with
      Gardner's syndrome: case report.
AB  - As osteomas of the bones including the jaws may be the initial symptom or
      clinical finding in the Gardner's syndrome, this entity should always be included
      in the differential diagnosis. A 20-year-old boy was referred to our clinic from
      another medical center. Extra-oral examination of the patient revealed an obvious
      asymmetry and disfigurement of the left mandibular corpus, angle and ramus. A
      panoramic radiograph revealed two huge osteomas at the angle, ramus and two
      smaller osteomas at the inferior border of the mandible. At the same time, there
      were an impacted canine and premolar. Diffuse sclerosis of the whole mandible was
      also seen. Upon the suspicion of Gardner's syndrome, barium passage radiographs
      of the intestine were requested and multiple polyps were observed. All of these
      findings led us to the diagnosis of Gardner's syndrome. The oral and
      maxillofacial surgeon and the dentist needs to be aware of the components of this
      entity because manifestations in the head and neck including epidermoid cysts,
      osteomas, odontomas, exostoses, supernumerary and impacted teeth are common. At
      the same time, osteomas causing disfigurement on the face related with Gardner's
      syndrome with increased uptake in scintigraphic examination should be treated by
      surgical excision of the lesions.

PMID- 14656577
TI  - Use of control sample for estimation of prediction error in multivariate
      determination of lidocaine solutions with non-column chromatographic diode array
      UV spectroscopy.
AB  - The aim of this study was to investigate the ability of a control sample, of
      known content and identity, to diagnose and correct errors in the predictions
      when the same multivariate calibration model was used for analysis of new samples
      over time. A calibration set consisting of 16 samples with a known content of
      lidocaine was analysed and two external test sets, A and B, were used for the
      validation. Test set A contained 15 samples with different concentrations of
      lidocaine and test set B contained three samples with different lidocaine
      content, which were analysed six times in order to obtain a measure of
      repeatability. The multivariate calibration was done with PLS regression on UV
      spectra collected between 245 and 290 nm. A representative UV spectrum was
      exported from the collected DAD files by two methods, average spectrum over the
      whole file and average spectrum over the sample plug. Test set A was analysed
      further on another three occasions together with a control sample. The results
      showed that the control sample could be used to give a diagnosis and estimate of
      the prediction error. Moreover, the measured prediction error of the control
      sample could also be used to correct the predictions, thereby reducing the
      prediction error. Finally, some practical considerations regarding use of the
      proposed DAD method with a control sample are presented. The procedure suggested
      could lead to an efficient analytical approach where the same calibration model
      could be used over time without recalibration, which may be attractive in
      industrial quality control or screening analysis in pharmaceutical research.

PMID- 14656578
TI  - Relation between retention factors of immunosuppressive drugs in microemulsion
      electrokinetic chromatography with biosurfactants and octanol-water partition
      coefficients.
AB  - Retention (capacity) factors (k' values) of immunosuppressive drugs were
      determined in microemulsion electrokinetic chromatography (MEEKC) systems as a
      tool for the indirect estimation of partition coefficients (POW) between 1
      octanol and water. The microemulsions were based on phosphatidylcholine (PC) and
      bile acids (BAs) as biosurfactants and isopropyl myristate (IPM) as oil.
      Immunosuppressants were azathioprine (AZA), mycophenolate mofetil (MMF),
      tacrolimus (FK506) and cyclosporine A (CyA). Capacity factors of the analytes
      were determined from electrophoretic mobilities using an aqueous phosphate buffer
      (20 mM; pH 7.5) for all the systems. Retention was compared with that in the most
      commonly used microemulsion based on sodium dodecyl sulphate (SDS). logPOW versus
      logk' calibration lines were constructed using reference compounds with known
      POW. In addition, data of logPOW of the immunosuppressants were determined by
      partitioning between octanol and water, and were calculated by the aid of
      computer program. A different sequence of logPOW for two analytes was found in
      the biosurfactant-based systems compared with the SDS-containing one. Excellent
      agreement was observed between the logPOW values derived from the microemulsions
      containing deoxycholate compared with the data determined by partitioning between
      octanol and water. It was concluded that the retention factors in the systems
      with biosurfactants are good estimators for the partitioning in biological
      systems.

PMID- 14656579
TI  - A validated LC method for imatinib mesylate.
AB  - An isocratic reversed-phase liquid chromatography method with UV detection has
      been developed for the purity evaluation of imatinib mesylate in bulk drug. The
      method is selective and is capable of detecting all process intermediates and
      other related compounds, which may be present at trace levels in the drug
      substance. The method was validated on a Symmetry Shield RP18 analytical column
      (150 x 4.6 mm, 5 microm), mobile phase consisting of 30 mM sodium octane
      sulphonic acid in 10 mM aqueous KH2PO4 (pH 2.5 with H3PO4): MeOH in the ratio of
      42:58 v/v. The flow rate was set at 1.0 ml/min and the column was maintained at
      room temperature. The injection volume was set to 10 microl and the detector was
      set at a wavelength of 237 nm. The method was validated in terms of system
      precision, method precision, linearity, accuracy, limit of detection and limit of
      quantification.

PMID- 14656580
TI  - Comparison between mono- and bi-exponential models for reaction kinetics in the
      immunoradiometric assay of neuron-specific enolase.
AB  - This paper studies the kinetics of the antigen-antibody reactions involved in the
      analytical determination of neuron-specific enolase (NSE) by means of radiometric
      immunoassay (IRMA). For the global process, kinetics were found to be dependent
      on analyte and labelled antibody concentrations, such dependence fitting with the
      models described in previous papers. Viscosity results clearly indicate its
      negative influence on the direct reaction rate. Ionic strength shows noticeable
      but not too relevant effects, which suggests that the variation caused by the
      glycerol addition is not due to the influence of the dielectric constant of the
      solutions used. The effect of temperature shows activation parameters similar to
      the viscous flow energy of water, which suggests diffusion control for the global
      process. The analysis of the kinetic data of the experiences conducted can be
      explained by admitting that the antigen-antibody binding takes place through two
      different binding site types.

PMID- 14656581
TI  - Trimipramine determination in pharmaceutical preparations with an automated
      multicommutated reversed-flow system.
AB  - In this work an automated multicommutated flow methodology was implemented for
      the spectrophotometric determination of trimipramine in pharmaceutical
      preparations by oxidation with ammonium monovanadate in acidic medium. The
      developed procedure exploits a new approach for sample/reagent intermixing by
      combining binary sampling with flow-reversal. Rather than inserting the sample as
      a single continuous volume the intercalation of multiple small sample and reagent
      aliquots, under a time-based control, created multiple reaction interfaces that
      promoted reaction zone homogenisation even in limited dispersion conditions.
      Additionally, the reaction interfaces were reversed, increasing mutual zone
      penetration, which contributed to a faster reaction development while assuring a
      low dispersion pattern. A linear range of determination was verified for
      trimipramine concentrations between 1.0 and 18.0 microg ml(-1) with a relative
      standard deviation (n=10) lower than 1.69% and a sample throughput of about 26
      samples per hour. The results were in agreement with those obtained by the
      reference procedure with relative deviations lower then 2.37%.

PMID- 14656582
TI  - Testimony of the correlation between DHEA and bioavailable testosterone using a
      biochromatographic concept: effect of two salts.
AB  - In a previous paper (C. Andre et al., submitted to J. Chromatogr. B) a
      mathematical model based on the Langmuir theory was developed to visualize the
      competition effect between testosterone and deshydroepiandrosterone (DHEA) for
      their identical human serum albumin (HSA) binding cavity. In this work, the
      thermodynamic mechanisms of (i) the binding of two hormones, DHEA and
      testosterone to HSA and (ii) the testosterone displacement of its HSA binding
      cavity by DHEA was studied by biochromatography. The Na+ cation effect used as
      physico-chemical marker of these binding processes was clearly described. The
      Gibbs free energy value (DeltaGo ) of the displacement equilibrium was always
      negative demonstrating that DHEA well displaced testosterone of its HSA binding
      cavity. The thermodynamic data also showed that this displacement equilibrium was
      enthalpically controlled. Moreover, the effect of (Mg2+) concentration (x') on
      the two binding mechanisms was analyzed. It appeared that for old men with a
      deficit of testosterone, Mg(2+) supplementation during treatment with DHEA can
      increased the free testosterone concentration and its biological effect. All
      these results must be confirmed by in vivo test.

PMID- 14656583
TI  - Flow injection and HPLC determination of furosemide using pulsed amperometric
      detection at microelectrodes.
AB  - The flow-injection and HPLC determination of the diuretic drug furosemide using
      pulsed amperometric detection (PAD) at cylindrical carbon fibre microelectrodes
      (CFMEs) is reported. Experimental conditions such as pH (6.5) and buffer
      concentration (0.05 mol l(-1) HPO4(2-)/H2PO4(-)) were optimized using square-wave
      voltammetry (SWV). Repetitive flow-injection amperometric measurements at +1.25 V
      for furosemide showed a continuous decrease in the peak current, probably as a
      consequence of the microelectrode surface fouling. However, a suitable
      amperometric detection of furosemide was achieved using a PAD program consisting
      of a two-step potential waveform with alternating anodic and cathodic
      polarization. The anodic (detection) potential was +1.25 V (time of application
      0.1 s), and the cathodic (cleaning) potential was -0.20 V (t=0.2 s). A linear
      calibration graph was obtained for furosemide in the 5.0 x 10(-7)-1.0 x 10(-4)
      mol l(-1) concentration range, with a limit of detection of 1.7 x 10(-7) mol l(
      1). HPLC-PAD at carbon fibre microelectrodes was used for the determination of
      furosemide in the presence of several thiouracil drugs and oxytetracycline (OTC).
      The mobile phase selected was a 25:75 acetonitrile:5.0 x 10(-3) mol l(-1) NaH2PO4
      (pH 5.0) mixture. A linear calibration graph was obtained for furosemide in the 1
      100 microM range, with a limit of detection of 0.55 microM. The usefulness of
      this method for the determination of furosemide in real samples was evaluated by
      performing the analysis of commercial milk samples spiked with furosemide at a
      concentration level of 4.5 x 10(-7) mol l(-1) (150 ng ml(-1)), as well as with
      other thiouracil drugs and OTC. A mean recovery of 95+/-5% furosemide was
      obtained.

PMID- 14656584
TI  - Validation of a RP-HPLC method for the assay of formoterol and its related
      substances in formoterol fumarate dihydrate drug substance.
AB  - A stability-indicating reversed-phase high performance liquid chromatographic
      (HPLC) method has been developed and validated for the assay of formoterol
      fumarate and the related substances, namely, formoterol fumarate desformyl and
      formoterol fumarate acetamide analogs, in the active pharmaceutical ingredient.
      The separation was achieved by isocratic elution using an Alltech Alltima C18
      (150 x 4.6 mm) column, a mobile phase consisting of ammonium acetate (50 mM; pH
      5.0)-ethanol (65:35, v/v), a flow rate of 1.0 ml/min and UV detection at 242 nm.
      The detection and quantitation limits were 0.03 and 08 microg/ml, respectively,
      while the linear range of detection was between 0.03 and 255 microg/ml.
      Comparative determinations of formoterol fumarate in three lots of bulk drugs
      using the proposed HPLC method and the standard potentiometric titration method
      of pharmacopoeia show that both methods are equivalent for pure drug substance
      assay. However, the HPLC method allowed the separation and quantitation of the
      impurities not achievable with the official methods in the bulk drugs. This study
      shows that the proposed method is accurate, linear, and sensitive as stability
      indicating assay method for formoterol fumarate in the bulk drug.

PMID- 14656585
TI  - Validation of HPLC and UV spectrophotometric methods for the determination of
      meropenem in pharmaceutical dosage form.
AB  - A high-performance liquid chromatographic method and a UV spectrophotometric
      method for the quantitative determination of meropenem, a highly active
      carbapenem antibiotic, in powder for injection were developed in present work.
      The parameters linearity, precision, accuracy, specificity, robustness, limit of
      detection and limit of quantitation were studied according to International
      Conference on Harmonization guidelines. Chromatography was carried out by
      reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM
      monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with
      orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm.
      The samples were prepared in water and the stability of meropenem in aqueous
      solution at 4 and 25 degrees C was studied. The results were satisfactory with
      good stability after 24 h at 4 degrees C. Statistical analysis by Student's t
      test showed no significant difference between the results obtained by the two
      methods. The proposed methods are highly sensitive, precise and accurate and can
      be used for the reliable quantitation of meropenem in pharmaceutical dosage form.

PMID- 14656586
TI  - Determination of content uniformity and distribution characteristics of an
      investigational drug in its tablets dosage form and granule by ICP-AES.
AB  - An investigational drug (A) in its calcium salt form has been developed as the
      tablet dosage form. Monitoring drug distribution and uniformity in granules and
      tablets during early stage formulation/process development is critical for drug
      product quality control and process robustness. In this report, an efficient and
      reliable analytical method for monitoring drug compound A uniformity and
      distribution has been developed by analyzing calcium, the counter ion of the drug
      substance, by Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES).
      In this method, calcium in compound A granule and tablet samples was digested
      with 1 M hydrochloric acid by heating at 90 degrees C for 2 h. The resulting
      suspension was centrifuged, and the supernatant was directly aspirated into an
      ICP-AES. This method has been validated to demonstrate satisfactory precision,
      accuracy, specificity and sensitivity. Finally, this method has been used to
      analyze sieve fraction granules and tablets of drug compound A. The data
      generated were highly comparable to those by validated HPLC methods (UV method
      can not be applicable due to significant bias). In comparison with HPLC methods,
      this method demonstrates a significantly improved efficiency with very short
      analysis time (1 min per sample), and can be used as an excellent alternative for
      UV and HPLC methods to support formulation screening.

PMID- 14656587
TI  - A gas chromatographic method for the indirect determination of hydroxylamine in
      pharmaceutical preparations: conversion into nitrous oxide.
AB  - A simple, sensitive, and selective headspace gas-chromatographic method has been
      developed for measuring hydroxylamine (HA) in a variety of sample matrices
      including pharmaceutical formulations. This procedure relies on converting HA
      into nitrous oxide (N2O), which is a single-step reaction that is carried out
      directly in a heated headspace vial. The gaseous products are then analyzed by
      headspace capillary gas chromatography. Several detection strategies were
      evaluated and electron capture provided the best sensitivity (4 parts-per-billion
      (ppb)) while the mass selective and thermal conductivity values were higher (14
      ppb and 1.4 parts-per-million (ppm), respectively). The method's linear dynamic
      range spans two to four decades with a run-to-run precision that was better than
      5% R.S.D. (n=7). The reagent concentrations (oxidant, buffer) strongly impact the
      N2O signal and the greatest response was obtained for solutions that contained
      equimolar amounts of reactants. HA was efficiently (98%) recovered from a sample
      matrix that contained only the active pharmaceutical ingredient (API) but the
      recovery was lower (83%) when excipients were present.

PMID- 14656588
TI  - Direct determination of triamterene by potentiometry using a coated wire
      selective electrode.
AB  - A coated wire triamterene-selective electrode based on the incorporation of a
      triamterene-tetraphenylborate ion-pair in a poly(vinylchloride) coating membrane
      was constructed. The influence of membrane composition, temperature, pH of the
      test solution, and foreign ions on the electrode performance were investigated.
      The electrode showed a Nernstian response over a triamterene concentration range
      from 1.0 x 10(-6) to 3.5 x 10(-2) M, at 25 degrees C, and was found to be very
      selective, precise, and usable within the pH range 4.5-7.5. The standard
      electrode potentials, E degrees, were determined at 15, 20, 25, 30, 35, 40 and 45
      degrees C and used to calculate the isothermal temperature coefficient (dE
      degrees /dt) of the electrode. Temperatures higher than 45 degrees C seriously
      affected the electrode performance. The electrode was successfully applied to the
      potentiometric determination of triamterene hydrochloride both in pure solutions
      and in pharmaceutical preparations.

PMID- 14656589
TI  - Amperometric biosensor based on monoamine oxidase (MAO) immobilized in sol-gel
      film for benzydamine determination in pharmaceuticals.
AB  - The development and application of a flow-through amperometric biosensor for
      benzydamine determination in anti-inflammatory drugs is described. The biosensor
      was obtained by physical entrapment of monoamine oxidase in a sol-gel film
      applied on platinum or carbon paste conducting support. The sol-gel membranes
      were prepared using an optimum concentration of 3-aminopropyltriethoxy silane, 2
      (3,4-epoxycyclohexyl)ethyl-trimethoxy silane, double distilled water saturated
      with polyethylene glycol 6000 and HCl. The developed biosensors were incorporated
      in a single channel flow injection system to enable the determination of
      benzydamine in the concentration range of 0.05-2.5 mmol l(-1) (with platinum
      based electrode) or within 0.1-2.5 mmol l(-1) (carbon paste based electrode). The
      operational stability of the bioanalytical system developed was about 3 months
      permitting approximately 4700 substrate measurements. The flow injection system
      developed enables a sampling rate of 20-25 samples h(-1) and relative S.D. of
      results less than 4%. The analytical usefulness of the proposed procedure was
      evaluated through analysis of commercial pharmaceutical products containing
      benzydamine, available on the Portuguese market. The results obtained did not
      differ significantly from the values resulting from analysis of the same products
      by the method described in the BP Pharmacopoeia.

PMID- 14656590
TI  - Determination of cisapride, its oxidation product, propyl and butyl parabens in
      pharmaceutical dosage form by reversed-phase liquid chromatography.
AB  - A simple, rapid and reproducible high-performance liquid chromatography (HPLC)
      assay for cisapride, its oxidation product (OP), propyl and butyl parabens in a
      pharmaceutical formulation is described. Chromatography was performed at room
      temperature by pumping acetonitrile-20 mM phosphate buffer pH 7 (50:50, v/v) at
      1.5 ml min(-1) through C8 reversed-phase column. Cisapride, OP, propyl and butyl
      parabens were detected at 276 nm and were eluted at 9.7, 3.1, 5.1 and 7.1 min,
      respectively. Calibration plots were linear (r>0.999) for all compounds from 0.5
      to 200 microg ml(-1) for cisapride and OP and 0.1-200 microg ml(-1) for propyl
      and butyl parabens. Detection limits for cisapride, OP, propyl and butyl parabens
      were 40, 46, 48 and 54 ng ml(-1), respectively. Forced degradation investigations
      showed that cisapride does not undergo degradation under heat, acidic and basic
      conditions but it was susceptible to oxidation. The proposed method was
      successfully applied to the assay of cisapride in the presence of preservatives
      and OP in a commercial suspension.

PMID- 14656591
TI  - Identification of oxidative degradates of the TRIS salt of a 5,6,7,8-tetrahydro
      1,8-naphthyridine derivative by LC/MS/MS and NMR spectroscopy--interactions
      between the active pharmaceutical ingredient and its counterion.
AB  - The Tris(hydroxymethyl)aminomethane (TRIS) salt of a substituted 5,6,7,8
      tetrahydro-1,8-naphthyridine compound (I) in a mannitol-based formulation was
      stressed at various conditions. Liquid chromatography/mass spectrometry (LC/MS)
      and liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses of the
      stressed samples revealed that oxidation and dimerization were the primary
      degradation pathways for this compound. 1H- and 13C-nuclear magnetic resonance
      (NMR) spectroscopy were used to characterize the isolated dimers. The aromatized
      degradate, N-oxide, amide, and three dimeric products were all confirmed by
      either LC/MS using authentic standards or NMR spectroscopy. In general, the
      aromatized product was always the primary degradate produced under all stress
      conditions. When stressed at 80 degrees C, the TRIS counterion also underwent
      thermal degradation to yield formaldehyde in situ which reacted with the parent
      compound to form a unique methylene-bridged dimeric product and an N-formyl
      degradate. A minor condensation product between the compound I and the TRIS
      counterion was also detected in the 80 degrees C stressed samples. Under 40
      degrees C/75% RH stress conditions, TRIS derived degradates were insignificant,
      while dimers formed by compound I became predominant. In addition, two
      hydroxylated products (7-OH and 5-OH) were also detected. Mechanisms for the
      formation of the oxidative and dimeric degradates were proposed.

PMID- 14656592
TI  - An HPLC method for the determination of atorvastatin and its impurities in bulk
      drug and tablets.
AB  - A simple high-performance liquid chromatographic (HPLC) method was developed for
      the analysis of atorvastatin (AT) and its impurities in bulk drug and tablets.
      This method has shown good resolution for AT, desfluoro-atorvastatin (DFAT),
      diastereomer-atorvastatin (DSAT), unknown impurities and formulation excipients
      of tablets. A gradient reverse-phase HPLC assay was used with UV detection. Some
      solvent systems prepared using methanol or acetonitrile and water or buffer
      systems with different pH values were tested. Capacity factors of related
      substances were calculated at all tested systems. Best resolution has been
      determined using a Luna C18 column with acetonitrile-ammonium acetate buffer pH 4
      tetrahydrofuran (THF) as mobile phase. Samples were eluted gradiently with the
      mobile phase at flowrate 1.0 ml min(-1) and detected at 248 nm. The proposed
      method was applied to the determination of impurities and were found to contain
      0.057-0.081, 0.072-0.097, 0.608-0.664% of the DFAT, DSAT and total impurity,
      respectively.

PMID- 14656593
TI  - Flow-injection amperometric determination of dopamine in pharmaceuticals using a
      polyphenol oxidase biosensor obtained from soursop pulp.
AB  - The amperometric determination of dopamine (Do) in pharmaceuticals formulations
      by flow injection analysis (FIA) is proposed. An enzymatically modified carbon
      paste electrode constituted by 25% (w/w) of polyphenol oxidase obtained from
      Annona muricata L. tissue, 30% (w/w) of graphite, 30% (w/w) of silicone and 15%
      (w/w) of 7,7,8,8 tetracyanoquinodimethane (TCNQ), was used as flow-through
      detector. The flow amperometric detection was carried out at a potential of 0.10
      V (vs. Ag/AgCl) when an injected sample volume of 250 microl was inserted on a
      0.3 M phosphate buffer carrier solution (pH 7.8) flowing at 2.5 ml/min. The
      developed biosensor showed good stability and reproducibility, enabling up to 500
      determinations in 60 days, without considerable loss of enzymatic activity. The
      FIA system presented a linear response to Do concentrations in the interval from
      2 x 10(-2) to 2 x 10(-4) M, with relative standard deviations lower than 1.5%.
      The kinetic parameter K(M) for the soluble and immobilized enzyme was 1.45 x 10(
      2) and 1.91 x 10(-2) M, respectively. In the analyses of different commercially
      pharmaceutical formulations a relative deviation lower than about 3.4% was
      obtained.

PMID- 14656594
TI  - A simple and sensitive chemiluminescence method for the determination of
      tiopronin for a pharmaceutical formulation.
AB  - Here we report a rather simple and convenient chemiluminescence (CL) method for
      the determination of tiopronin. It was based that tiopronin could greatly enhance
      CL between H2O2 and luminol in a basic alkaline solution. Light emission is
      intense, and even with a simple setup a high sensitivity could be achieved. The
      linear range was 3 mM-500 nM with a detection limit of 200 nM. Singlet oxygen and
      hydroxyl radical were suggested to be produced in this reaction and was
      responsible for the CL of tiopronin. As a preliminary application, this simple
      method has been successfully applied into the determination of tiopronin in a
      pharmaceutical formulation.

PMID- 14656595
TI  - Three simultaneous dissolution profiles on a solid pharmaceutical formulation by
      a FIA manifold provided with a single spectrophotometric detector.
AB  - This article deals with the simultaneous determination of three dissolution
      profiles in the same pharmaceutical formulation. The officially proposed
      procedure from the pharmacopoeias is adapted to the FIA methodology to obtain the
      officially recommended profile or "global profile", and two "individual"
      profiles, corresponding to dissolution rate of two different active principles
      present in the formulation; both drugs have overlapped UV-vis spectra. The
      simultaneous determination of several profiles is based on the derivative spectra
      and the zero crossing mathematical procedure for the "individual" profiles of an
      active principle; the "global" profile of the formulation is obtained from the
      order zero derivative. The empirical profiles were adjusted by regression
      analysis using the three-parameter (Higuchi equation) plot method which was
      selected as the most suitable. The analytical errors when the concentration of
      one drug is very small or very high are also checked.

PMID- 14656596
TI  - Determination of hydrogen peroxide concentration in antiseptic solutions using
      portable near-infrared system.
AB  - Hydrogen peroxide (H2O2) concentrations in antiseptic solutions (normally 3%
      H2O2) has been determined non-destructively using a portable near-infrared (NIR)
      analyzer. The spectral variation due to -OH band around 1400 nm in the second
      derivative spectra has been found as H2O2 concentration changes. Both multiple
      linear regression (MLR) and partial least squares (PLS) were employed to generate
      calibration models over the 1100-1720 nm range. The PLS calibration model showed
      the better calibration performance with a standard error of prediction (SEP) of
      0.16%. In order to validate the developed PLS calibration model, H2O2
      concentrations in commercial antiseptic solutions were predicted and compared
      with values from a conventional redox titration method. The results showed that
      NIR predictions had good correlation with conventional analysis values. The rapid
      and non-destructive determination of H2O2 in the antiseptic solution was
      successfully performed using portable NIR analyzer without any hazardous chemical
      solvents.

PMID- 14656597
TI  - Improving microdialysis extraction efficiency of lipophilic eicosanoids.
AB  - Microdialysis recovery of the lipophilic analytes prostaglandin B2, leukotriene
      B4 and C4 was studied in vitro. Relative recovery (RR) through different
      commercially-available microdialysis probes for prostaglandin B2 and leukotrienes
      was examined using different flow rates. The enhancing effect at different
      concentrations of binding agents such as alpha, beta, gamma-cyclodextrins (alpha,
      beta, gamma-CD) on the microdialysis RR for different eicosanoids was evaluated.
      Small organic molecules such as ethanol, propylene glycol and dimethyl sulfoxide
      (DMSO) were studied in terms of their effect on enhancing RR. Inclusion of
      arachidonic acid in either the perfusion fluid or the sample medium caused the
      microdialysis RR for these hydrophobic analytes to be increased.

PMID- 14656598
TI  - Quantitation of PGE9509924, a novel, nonfluorinated quinolone, in rat plasma
      using liquid chromatography electrospray-tandem mass spectrometry following solid
      phase extraction sample clean-up in a 96-well format.
AB  - PGE9509924, a novel nonfluorinated quinolone, is a potent antibacterial agent
      with a broad spectrum of activity. A semi-automated method using 96-well format,
      solid-phase extraction has been developed for quantitating PGE9509924 in rat
      plasma. The Waters Oasis HLB extraction plate containing a polymeric packing
      material was found to give the best overall recoveries. All liquid transfer steps
      other than aliquoting the plasma are accomplished using a 96-channel pipettor.
      Reverse-phase HPLC with electrospray/MS/MS detection using selective reaction
      monitoring is used to quantitate the samples. Stable isotopically labeled
      PGE9509924 is used as the internal standard. The assay is linear over the range
      from 0.01 to 10 ug/ml. Excellent precision is obtained within a single run and
      between multiple runs performed on different days. CVs of <6% were observed. The
      combination of the semi-automated, 96-well parallel sample processing and the
      short runtime on the LC/MS/MS results in a high throughput assay with reduced
      operator interaction.

PMID- 14656599
TI  - Determination of hydroxyproline in plasma and tissue using electrospray mass
      spectrometry.
AB  - A simple and highly specific method that was developed for the determination of
      hydroxyproline in biological samples is described. This method could potentially
      be used for monitoring pathological conditions related to collagen degradation,
      as well as for screening remedial pharmaceuticals for efficacy. Tissue or plasma
      samples were prepared by hydrolysis and their hydroxyproline content was
      determined using spiked calibration curves and LC/MS/MS. Specificity of the
      method was evaluated using an API Time-Of-Flight (TOF) LC/MS to expose potential
      interferences. The method proposed here appears to be selective, convenient,
      precise (<10% R.S.D.), accurate (<10% RE), and sensitive over a linear range of
      0.010-10 microg/ml.

PMID- 14656600
TI  - HPLC-MS/MS determination of a peptide conjugate prodrug of doxorubicin, and its
      active metabolites, leucine-doxorubicin and doxorubicin, in dog and rat plasma.
AB  - A HPLC-MS/MS Electrospray (ESI) method was developed and validated to quantify a
      peptide conjugate prodrug of doxorubicin (Dox-Con) and its active metabolites
      leucine-doxorubicin (Leu-Dox) and doxorubicin (Dox) in dog and rat plasma. The
      analytes were extracted from plasma by solid-phase extraction on a Bond Elut C8
      cartridge and eluted with chloroform-methanol (2:1). Eluates were evaporated and
      reconstituted in acetonitrile-5 microM sodium trifluoroacetate in 0.1% aqueous
      formic acid (20:80) and injected onto a Waters Oasis HLB column. Analytes were
      eluted from the column with a solvent gradient into the mass analyzer. The ions
      were quantified in the selected reaction-monitoring mode (SRM), using positive
      ions, on a triple quadrupole mass spectrometer. The lower limits of
      quantification for Dox-Con, Leu-Dox, and Dox in plasma, were approximately 5, 1
      (dog)/6 (rat), and 0.5 ng/ml, respectively. Intra- and inter-assay accuracy (% of
      nominal concentration) and precision (%CV) for all analytes were within 15 and
      16%, respectively.

PMID- 14656601
TI  - A 1H NMR-based metabonomic study of urine and plasma samples obtained from
      healthy human subjects.
AB  - The aim of the study was to assess the feasibility of metabonomics in clinical
      studies. A 1H nuclear magnetic resonance (NMR)-based metabonomic analysis was
      performed on plasma and urine samples obtained from a group of 12 healthy male
      subjects on two separate study days 14 days apart. The subjects were fed a
      standard diet and plasma and urine samples were obtained on both days. The 1H NMR
      spectra obtained for urine and plasma samples were analysed using principal
      components analysis (PCA) in order to generate metabonomic data. In plasma there
      was relatively little variability between subjects and study days. In the case of
      endogenous urinary metabolite profiles there was considerable inter-subject
      variability, but less intra-subject variation. In all subjects diurnal variation
      was seen with urine samples. This suggests the possibility to collect consistent
      metabonomics data in clinical studies.

PMID- 14656602
TI  - Electrochemical detection of DNA immobilized on gold colloid particles modified
      self-assembled monolayer electrode with silver nanoparticle label.
AB  - The target DNA was immobilized successfully on gold colloid particles associated
      with a cysteamine monolayer on gold electrode surface. Self-assembly of colloidal
      Au onto a cysteamine modified gold electrode can enlarge the electrode surface
      area and enhance greatly the amount of immobilized single stranded DNA (ssDNA).
      The electron-transfer processes of [Fe(CN)6](4-)/[Fe(CN)6](3-) on the gold
      surface were blocked due to the procedures of the target DNA immobilization,
      which was investigated by impedance spectroscopy. Then single stranded target DNA
      immobilized on the gold electrode hybridized with the silver nanoparticle
      oligonucleotide DNA probe, followed by the release of the silver metal atoms
      anchored on the hybrids by oxidative metal dissolution, and the indirect
      determination of the released solubilized Ag(I) ions by anodic stripping
      voltammetry (ASV) at a carbon fiber microelectrode. The results show that this
      method has good correlation for DNA detection in the range of 10-800 pmol/l and
      allows the detection level as low as 5 pmol/l of the target oligonucleotides.

PMID- 14656603
TI  - Validated HPLC method for determination of LASSBio-581, a new heterocyclic N
      phenylpiperazine derivative, in rat plasma.
AB  - A rapid, simple and accurate high performance liquid chromatography (HPLC) method
      was developed and validated for the determination of LASSBio-581 (1-[1-(4-chloro
      phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine) in rat plasma using
      ketoconazole as internal standard. Plasma samples were deproteinized with
      methanol. A good chromatographic separation was achieved using a reversed phase
      C18 column. Mobile phase consisting of sodium dihydrogen phosphate monohydrate
      (pH 4.5, 0.02 M) and methanol mixture (35:65, v/v) was used at a flow rate of 1.0
      ml/min. The eluate was monitored using a UV detector at 248 nm. The retention
      times of LASSBio-581 and the internal standard were approximately 3.8 and 5.6
      min, respectively. The calibration curves were linear over the concentration
      range of 0.25-8.0 microg/ml with correlation coefficients >0.99. The limit of
      quantitation was 0.25 microg/ml. The accuracy of the method was >90%. The intra
      day relative standard deviation (R.S.D.) ranged from 6.15 to 10.52% at 0.4
      microg/ml, 7.44 to 13.81% at 1.5 microg/ml and 6.10 to 13.94% at 6.0 microg/ml.
      The inter-day R.S.D. were 9.54, 8.42 and 8.25% at 0.4, 1.5 and 6.0 microg/ml,
      respectively. No interference from endogenous substances or metabolites were
      observed. The method has been used to measure plasma concentrations of LASSBio
      581 in pharmacokinetic studies in rats.

PMID- 14656604
TI  - Direct injection HPLC method for the determination of selected benzodiazepines in
      plasma using a Hisep column.
AB  - A direct plasma injection HPLC method has been developed for the determination of
      selected benzodiazepines (nitrazepam, clobazam, oxazepam, lorazepam). The method
      uses an analytical hydrophobic shielded phase (Hisep) column equipped with a
      Hisep guard column, are easy to perform and requires 20 ul of a filtered plasma
      sample. The chromatographic run time is less than 15 min using a mobile phase of
      15:85 v/v acetonitrile-0.18 M ammonium acetate pH 2.5. The method is good for 175
      injections before replacement of the guard column. The method was linear in the
      range 0.5-18 ug ml(-1) (r>0.99, n=6) for the analytes with R.S.D. less than
      10.82%. Interday and intraday variability were found to be less than 14%. The
      limits of detection and quantitation were 0.16 (s/n>3) and 0.5 ug ml(-1)
      (s/n>10), respectively, for each of the four benzodiazepines.

PMID- 14656605
TI  - Potentiometric and voltammetric determination of methimazole.
AB  - The determination of methimazole was investigated by potentiometric titration in
      an alkaline medium involving its reaction with iodine and square wave voltammetry
      (SWV) in 0.1 mol/l Tris-HCl buffer at pH 7.2. In potentiometric titration, the
      range of determination was 10-500 micromol. A stoichiometric reaction was
      obtained within the concentration range 0.75-1.25 mol/l of sodium hydroxide by
      potentiometric titration. A linear calibration graph was obtained over the
      concentration range 1-700 micromol/l by SWV. The lowest concentration of
      methimazole detected was 0.5 micromol/l. The relative standard deviations
      (R.S.D.) were 0.81% in potentiometric titration and 2.89% in square wave
      voltammetric analysis of thyromazol tablets. The data showed that potentiometric
      titration using iodine in sodium hydroxide can be used for the determination of
      methimazole in drug samples without prior separation.

PMID- 14656606
TI  - Determination of bopindolol using the flow injection technique coupled with solid
      phase extraction.
AB  - In the proposed procedure, the determination of bopindolol using a flow injection
      analysis (FIA) technique, with spectrophotometric detection at 635 nm, is
      described. The method is based on the production of a green, water-soluble
      complex with ferric ions in acid medium. The automated lab-made FIA system was
      used for the direct determination of bopindolol in tablets. Bopindolol was
      adsorbed onto the solid phase in a mini-column, which was integrated directly
      into the flow system. The positive feature of the use of solid phase extraction
      (SPE) was the pre-concentration of bopindolol (seven times). The sample
      throughput was 50 samples per hour. Using the SPE method, bopindolol was
      determined with a linear range from 125 to 1000 microg ml(-1) (Relative standard
      deviation (R.S.D.)=1.87%), with a detection limit (3sigma) of 70 microg ml(-1).
      The method was applied to the determination of bopindolol in Sandonorm tablets.
      The results obtained were compared with a conventional HPLC method, both
      analytical techniques were in good agreement.

PMID- 14656608
TI  - Two derivative spectrophotometric methods for the simultaneous determination of
      lovastatin combined with three antioxidants.
AB  - A zero crossing and an algorithm bivariate calibration derivative method for the
      simultaneous determination of lovastatin combined separately with three
      antioxidants (ascorbic acid, quercetin and gallic acid) in synthetic mixtures are
      described. The aqueous or methanolic solutions obeyed Beer's law in the
      concentration ranges of 3.20-17.36 microg/ml for lovastatin, 1.76-8.80 microg/ml
      for ascorbic acid, 1.41-7.04 microg/ml for gallic acid and 1.84-9.20 microg/ml
      for quercetin, for both methods, respectively. In the second derivative (2D) zero
      crossing method measurements were carried out at 238.4 nm for lovastatin and
      265.6 nm for ascorbic acid, 247.7 nm for lovastatin and 281.1 nm for quercetin,
      251.8 nm for lovastatin and 267.6 nm for gallic acid. In the first derivative
      (1D) bivariate spectrophotometric method an optimum pair of wavelengths was
      chosen for the determination of different binary mixtures. The proposed
      procedures were successfully applied to the simultaneous determination of
      lovastatin and different antioxidants in mixtures with high percentage of
      recovery, 98.3-100.4% for lovastatin, 98.3-98.6% for ascorbic acid, 99.0-99.8%
      for quercetin and 100.5-101.1% for gallic acid and good precision. In addition,
      the results from the above procedures were verified by using partial least
      squares (PLS) multivariate calibration method.

PMID- 14656607
TI  - Simultaneous separation and determination of active components in Cordyceps
      sinensis and Cordyceps militarris by LC/ESI-MS.
AB  - A simple and rapid isocratic LC/MS coupled with electrospray ionization (ESI)
      method for simultaneous separation and determination of adenine, hypoxanthine,
      adenosine and cordycepin in Cordyceps sinensis (Cs) and its substitutes was
      developed. 2-Chloroadenosine was used as internal standard for this assay. The
      optimum separation for these analytes was achieved using the mixture of water,
      methanol and formic acid (85:14:1, v/v/v) as a mobile phase and a 2.0 x 150 mm
      Shimadzu VP-ODS column. Selective ion monitoring (SIM) mode ([M+H]+ at m/z 136,
      137, 268, 252 and 302) was used for quantitative analysis of above four active
      components. The regression equations were liner in the range of 1.4-140.0 microg
      ml(-1) for adenine, 0.6-117.5 microg ml(-1) for hypoxanthine, 0.5-128.5 microg
      ml(-1) for adenosine and 0.5-131.5 microg ml(-1) for cordycepin. The limits of
      quantitation (LOQ) and detection (LOD) were, respectively 1.4 and 0.5 microg ml(
      1) for adenine, 0.6 and 0.2 microg ml(-1) for hypoxanthine, 0.5 and 0.1 microg
      ml(-1) for adenosine and cordycepin. The recoveries of four constituents were
      from 93.5 to 107.0%. The nucleoside contents of various types of natural Cs and
      its substitutes were determined and compared with this developed method.

PMID- 14656609
TI  - Specific determination of myo-inositol in multivitamin pharmaceutical
      preparations by a flow injection system using a myo-inositol dehydrogenase
      reactor coupled with a glucose eliminating enzyme reactor.
AB  - A flow injection system for myo-inositol determination in multivitamin
      pharmaceutical preparations using two enzyme reactors was developed. Myo-inositol
      was detected using a fluorophotometer, to measure the fluorescence of NADH
      produced from NAD+ by a myo-inositol dehydrogenase reactor (IDR) containing myo
      inositol dehydrogenase immobilized on porous glass. Enhanced interference due to
      excess glucose included in a multivitamin pharmaceutical preparation as a
      sweetener was eliminated by a glucose eliminating reactor (GER) co-immobilized
      with three enzymes (glucose oxidase, mutarotase and catalase). The calibration
      coefficient for the standard curve was 0.9993 for myo-inositol detection in the
      range of 1-5 microg/ml. Myo-inositol was determined even in the presence of
      glucose concentrations of 140-420 microg/ml. The recovery of myo-inositol added
      to the multivitamin pharmaceutical preparation was 99.6% (n=9).

PMID- 14656610
TI  - Characterization of eptifibatide during drug formulation stability assays.
AB  - The objective of the study was to determine the identity of a new impurity
      detected in HPLC chromatograms of research samples of eptifibatide manufactured
      by a new process and formulated into drug product. The identification of the
      unknown impurity was required in order to understand the mechanism of its
      formation. The analysis was performed by using tandem mass spectrometers coupled
      with a reversed-phase gradient HPLC system. The unknown compound was then
      structurally elucidated by matrix-assisted laser desorption ionization (MALDI)
      tandem mass spectrometry. The mass spectrometric results showed that the
      protonated molecular ion of the unknown compound was m/z 862.3347 with molecular
      formula: C(36)H(52)N(11)O(10)S(2). The unknown compound was a linear peptide and
      was related to Asp-clipped eptifibatide. It was formed from Asp-clipped
      eptifibatide by the reaction of the amino group of tryptophan moiety with
      formaldehyde followed by electrophilic attack on the nitrogen of indole.

PMID- 14656611
TI  - Increased plasma levels of lipoprotein(a) and the risk of idiopathic and
      recurrent venous thromboembolism.
AB  - PURPOSE: Elevated lipoprotein(a) [Lp(a)] levels are a recognized risk factor for
      cardiovascular disease; however, little is known about their effects on venous
      thromboembolism. METHODS: We conducted a case-control study of 603 adult patients
      with a history of venous thromboembolism (at least 6 months after the acute
      event) and 430 healthy subjects. We measured Lp(a), homocysteine, and
      antithrombin levels, factor V Leiden and factor II (prothrombin) polymorphisms,
      and anticardiolipin antibodies. RESULTS: Lp(a) levels >300 mg/L were found in 24%
      (n = 146) of the patients and in 13% (n = 58) of the controls (P = 0.005). In a
      multivariate analysis adjusted for acquired and hemostasis-related risk factors,
      there was an independent association between elevated (>300 mg/L) Lp(a) levels
      and venous thromboembolism (odds ratio = 2.1; 95% confidence interval: 1.4 to
      3.2; P = 0.002). These results were confirmed in the 341 patients with idiopathic
      venous thromboembolism, as well as in those with recurrent thromboembolism.
      CONCLUSION: These results show that Lp(a) is an independent risk factor for
      venous thromboembolism in adults, suggesting that it may be involved in the
      pathogenesis of idiopathic and recurrent disease.

PMID- 14656612
TI  - Effects of an early invasive strategy on ischemia and exercise tolerance among
      patients with unstable coronary artery disease.
AB  - BACKGROUND: An early invasive approach after an episode of unstable coronary
      artery disease has beneficial effects on mortality and myocardial infarction, but
      its effects on exercise capacity and ischemia have not been investigated.
      METHODS: In the Fast Revascularisation during InStability in Coronary disease
      (FRISC) II trial, 2457 patients with unstable coronary artery disease were
      assigned randomly to an early invasive or noninvasive strategy. A symptom-limited
      bicycle exercise test was performed before discharge in the noninvasive group and
      after 3 months in both groups. RESULTS: At 3 months, 86% (1046/1222) of the
      patients in the invasive group and 81% (995/1235) in the noninvasive group
      performed the exercise test. Before the test, revascularization had been
      performed in 78% (n = 819) of these patients in the invasive group compared with
      28% (n = 281) of those in the noninvasive group. The mean (+/- SD) exercise
      capacity was higher (6.4 +/- 1.9 vs. 6.2 +/- 1.9 metabolic equivalents [METS], P
      <0.01), and the occurrence of ischemia lower (23% [229/1004] vs. 36% [352/966], P
      <0.001) in the invasive group. In the noninvasive group, 882 patients performed
      an exercise test both predischarge and at 3 months. If a revascularization
      procedure was performed (n = 210), exercise tolerance increased from 5.1 +/- 1.4
      to 6.0 +/- 1.8 METS (P <0.001) and the number of patients with ST depression
      decreased from 65% (131/203) to 31% (63/203) (P <0.001). Without
      revascularization (n = 670), exercise tolerance increased from 5.9 +/- 2.2 to 6.3
      +/- 1.9 METS (P <0.001), and there were no differences in the occurrence of
      ischemia. CONCLUSION: In unstable coronary artery disease, an invasive strategy
      improves exercise tolerance and reduces exercise-induced ischemia.

PMID- 14656613
TI  - Prognostic importance of new small Q waves following non-ST-elevation acute
      coronary syndromes.
AB  - PURPOSE: To investigate the prognostic importance of new small Q waves following
      an acute coronary syndrome. METHODS: We assessed 6-month mortality in 10501
      patients with non-ST-elevation acute coronary syndromes who had survived 30 days
      and had both admission and 30-day electrocardiograms. Patients were stratified by
      whether they had no new Q waves (n = 9447), new 30- to 40-ms Q waves (n = 733),
      or new > or =40-ms Q waves (n = 321). RESULTS: Mortality was higher in patients
      with 30- to 40-ms Q waves than in those with no new Q waves (3.4% [25/733] vs.
      2.4% [227/9447], P = 0.005), and even higher in those with > or =40-ms Q waves
      (5.3% [17/321], P = 0.002). After adjustment for baseline risk predictors,
      mortality remained higher in patients with new 30- to 40-ms Q waves (odds ratio
      [OR] = 1.30; 95% confidence interval [CI]: 0.85 to 1.98; P = 0.23) and those with
      new > or =40-ms Q waves (OR = 1.87; 95% CI: 1.13 to 3.09; P = 0.01). CONCLUSION:
      Patients with new small Q waves following a non-ST-elevation acute coronary
      syndrome are at increased risk of adverse outcomes. These small Q waves should be
      considered diagnostic of myocardial infarction. Further research should
      investigate whether even smaller QRS changes are prognostically important.

PMID- 14656614
TI  - Effects of individual self-management education on clinical, biological, and
      adherence outcomes in asthma.
AB  - BACKGROUND: Asthma guidelines urge teaching patients the knowledge and skills
      required for self-management, based on the assumption that education will lead to
      improved skills and better asthma control. METHODS: In a prospective, randomized
      controlled trial of 65 adults with mild-to-moderate asthma, we examined whether
      an educational self-management intervention would improve adherence to inhaled
      corticosteroid therapy, decrease markers of airway inflammation, and improve
      clinical control. Peak flow, symptoms, and adherence were monitored for 7 weeks.
      After a 1-week run-in, subjects were assigned randomly to either the educational
      intervention or control group. The 30-minute intervention was delivered and
      reinforced at biweekly intervals. RESULTS: Compared with the control group, the
      intervention group had improvements in adherence to inhaled corticosteroid
      therapy (by 30% vs. -5%, P = 0.01), self-reported control of asthma (by 14% vs.
      5%, P = 0.04), and perhaps quality of life (by 37% vs. 21%, P = 0.06). The
      direction of change for all other clinical outcomes was more favorable in the
      intervention group, but not significantly so. Markers of inflammation in sputum
      decreased more in the intervention group, with sputum eosinophils declining
      significantly (P = 0.02). CONCLUSION: In asthmatic patients treated with inhaled
      corticosteroids, education and training in self-management improves adherence
      with inhaled therapy, perceived control of asthma, and sputum eosinophilia.

PMID- 14656615
TI  - Diabetic neuropathic foot ulcers: predicting which ones will not heal.
AB  - PURPOSE: Neuropathic foot ulcers are a serious complication of diabetes. The
      purpose of this study was to develop a clinically useful prognostic model for
      identifying ulcers that are not likely to heal. METHODS: Using an administrative
      and medical records database from a large wound care system, we designed a cohort
      study of patients with diabetic neuropathic foot ulcer. Clinicians followed a
      standard algorithm of good wound care, wound debridement, and wound offloading.
      The outcome was a healed wound by week 20 of care. For patients with more than
      one wound, we investigate the wound labeled as the primary wound. We evaluated
      several prognostic models of varying mathematical complexity. RESULTS: We studied
      27630 patients with a diabetic neuropathic foot ulcer, of whom 12983 (47%) healed
      by week 20 of care. The simplest model counted 1 point each if the wound was
      older than 2 months, larger than 2 cm(2), or had a grade > or =3 (on a 6-point
      scale). The likelihood that a wound would not heal was 0.35 for a count of 0,
      0.47 for a count of 1, 0.66 for a count of 2, and 0.81 for a count of 3 in the
      validation data set. CONCLUSION: A simple prognostic model can be developed using
      prognostic factors that are already part of the wound care examination.
      Applications of this model could include determining who will do well with
      standard care and as an aid in the design of clinical trials.

PMID- 14656616
TI  - Projecting the cost-effectiveness of adherence interventions in persons with
      human immunodeficiency virus infection.
AB  - PURPOSE: To explore the cost-effectiveness of interventions to improve adherence
      to combination antiretroviral therapy in patients with human immunodeficiency
      virus (HIV) infection. METHODS: A simulation model of HIV infection,
      incorporating CD4 cell count and HIV ribonucleic acid levels as predictors of
      disease progression, was used to estimate the lifetime costs and quality-adjusted
      life expectancy associated with clinical interventions to improve adherence to
      antiretroviral therapy (e.g., directly observed therapy, automatic medication
      dispensers, beepers, portable alarms) in a clinical trial cohort with early
      disease (mean CD4 count, 350 cells/microL), a clinical trial cohort with advanced
      disease (mean CD4 count, 87 cells/microL), and an urban cohort (mean CD4 count,
      217 cells/microL). Data were from clinical trials, national databases, and
      published literature. RESULTS: For relatively healthy patients with early
      disease, interventions that reduced virologic failure rates by 10% increased
      quality-adjusted life expectancy by 3.2 months, whereas those that reduced
      failure by 80% increased quality-adjusted life expectancy by 34.8 months, as
      compared with standard care. The cost-effectiveness ratio was below 50000 US
      dollars per quality-adjusted life-year (QALY) for interventions costing 100 US
      dollars per month provided that failure rates were reduced by at least 10%, and
      for those costing 500 US dollars per month provided that failure rates were
      reduced by more than 50%. For both patients with advanced disease and those from
      an urban cohort, adherence interventions costing about 500 US dollars per month
      (e.g., directly observed therapy) had to reduce failure by about 25% to have cost
      effectiveness ratios below 50000 US dollars per QALY. CONCLUSION: In patients
      with lower baseline levels of adherence or advanced disease, even very expensive,
      moderately effective adherence interventions are likely to confer cost
      effectiveness benefits that compare favorably with other interventions.

PMID- 14656617
TI  - Patient care before and after percutaneous coronary artery interventions.
AB  - Care of the patient before and after percutaneous coronary interventions has
      changed largely because of the increased use of stents. Important patient
      management issues include the evaluation of chest pain after the procedure,
      recognition of acute vessel closure during the periprocedural period, management
      of the vascular access site, and prevention of contrast-induced renal
      dysfunction. Risk factor modification and drug therapies are important
      interventions for the secondary prevention of coronary events. Functional testing
      has a meaningful role in the evaluation of some patients after coronary
      intervention. It is important for the specialist in internal medicine to have a
      firm working knowledge of the various aspects of patient care before and after
      these procedures because their role in the management of these patients is
      increasing.

PMID- 14656618
TI  - Is airway remodeling clinically relevant in asthma?
AB  - The social and economic impact of asthma is substantial worldwide. Although
      current therapies targeting both airway inflammation and airway hyperreactivity
      effectively relieve and prevent symptoms in the majority of patients, some
      patients experience persistent symptoms and a progressive decline in lung
      function, described as irreversible or refractory asthma. Indeed, there are many
      unanswered questions about the role of airway remodeling in asthma. This review
      addresses several topics of controversy, including whether all patients with
      asthma demonstrate airway remodeling; the contribution of distinct airway
      resident cells to the development of remodeling; the role of biomarkers or
      noninvasive measurements in predicting airway remodeling; and the effectiveness
      of current therapies on airway remodeling and disease progression.

PMID- 14656619
TI  - Leukocyte count: a risk factor for coronary artery bypass graft mortality.

PMID- 14656620
TI  - Cases from the Osler Medical Service at Johns Hopkins University.
AB  - A 50-year-old African American woman presented with bilateral lower extremity
      pain, a history of falls during the past several months, and personality and
      behavior changes. She had been in good health until approximately 5 months before
      admission, when she began to fall with increasing frequency, often while going
      down a flight of stairs. She described these falls as her "legs giving out" and
      feeling very heavy and unsteady. There was no head trauma or loss of
      consciousness. Her daughter noticed that her gait had become somewhat unsteady
      during the last several months. Her family also noted a change in her personality
      at this time. Previously, she had been a very tidy person who took great care
      with her appearance, who was working as a customer service representative.
      However, she had become less social and very withdrawn. She had been observed
      putting on dirty clothes after showering, as well as eating constantly. The
      patient denied any fevers, chills, night sweats, headaches, vision changes, or
      tinnitus. She also denied any rashes, muscle pain, or intolerance to heat or
      cold. There was no history of seizure disorder or depression. Her past medical
      history was notable only for hypertension and being a passenger in a motor
      vehicle crash 1 year before admission. She denied any alcohol, tobacco, or
      illicit drug use, and had no travel history other than coming to the United
      States, as she was originally from Trinidad. On physical examination, she was a
      moderately obese African American woman with a flat affect, psychomotor slowing,
      and alopecia of the scalp. She was alert and oriented to person, place, and time,
      but had a score of 26 out of 30 on the Mini-Mental State Examination. She lost
      points only for recall; she had no difficulty with serial 7s. Her cranial nerves
      were intact and her speech was fluent, although sparse, and she did not make any
      paraphasic errors. Her muscle strength was 5/5 in both the upper and lower
      extremities. Reflexes were 2+ in the upper extremities and 1+ in the lower
      extremities, and toes were downgoing bilaterally. She had intact sensation to
      light touch and pinprick, but markedly diminished proprioception of her lower
      extremities bilaterally. She had a wide-based gait with a positive Romberg sign
      and was markedly ataxic. Rectal examination yielded a positive guaiac test with
      brown stool, normal tone, and no masses. The remainder of the physical
      examination was normal. Laboratory studies revealed pancytopenia with a
      hematocrit of 22.7% and a mean corpuscular volume of 118.2 fL. A peripheral smear
      that was performed on admission, prior to transfusion, revealed macrocytic red
      cells and hypersegmented neutrophils.

PMID- 14656621
TI  - Lipoprotein(a): another risk factor for venous thrombosis?

PMID- 14656622
TI  - Advantages of an early invasive approach in acute coronary syndromes.

PMID- 14656623
TI  - The economic viability of antiretroviral adherence interventions.

PMID- 14656624
TI  - Imatinib-associated pulmonary alveolar proteinosis.

PMID- 14656625
TI  - Mucormycosis as an etiology of cerebral hemorrhage in patients with chronic
      neutrophilic leukemia.

PMID- 14656626
TI  - Hypertensive crisis associated with venlafaxine.

PMID- 14656627
TI  - Rhabdomyolysis and hemolysis after use of Coutarea latiflora.

PMID- 14656628
TI  - An unusual axillary mass.

PMID- 14656629
TI  - Polyneuropathy following gastric bypass surgery.

PMID- 14656630
TI  - Solitary pulmonary artery myxoma manifesting as pulmonary embolism and subacute
      cor pulmonale.

PMID- 14656631
TI  - Cardiovascular magnetic resonance imaging demonstrates mitral valve endocarditis.

PMID- 14656632
TI  - Translation of academic discovery into societal benefit: proposal for a balanced
      approach--part 2.

PMID- 14656633
TI  - [Geriatric oncology: from conception to clinical practice].

PMID- 14656634
TI  - [Why to measure drug compliance?].

PMID- 14656636
TI  - [Patient compliance with drug therapy in temporal arteritis].
AB  - OBJECTIVE: To evaluate patient compliance with drug therapy in temporal arteritis
      and to determine the characteristics of compliant or non-compliant patients.
      METHODS: Inpatients and outpatients from an Internal Medicine Unit were
      interviewed. Compliance with drug dosage and administration time was assessed
      with a questionnaire for the following drugs: glucocorticoids, calcium, vitamin
      D, diphosphonates (prevention of glucocorticoid-induced osteoporosis). RESULTS:
      Forty-nine patients were interviewed (61% female, mean age = 73.7 years).
      Glucocorticoids were prescribed to 96% of the patients, calcium and vitamin D to
      86% and diphosphonates to 49%. Compliance with drug therapy was 87%, 60%, 68% and
      51%, respectively, for all treatments. It was independent from the disease
      duration. Male were more compliant than female (P = 0.012). CONCLUSION: Half of
      the patients with temporal arteritis are non-compliant with drug therapy. The
      questionnaire is simple. It can be used in everyday clinical practice to study
      and improve patient compliance.

PMID- 14656635
TI  - [Systemic lupus erythematosus in Tunisia. A multicentric study. About 295 cases].
AB  - PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease with a great
      clinical polymorphism. Wide variety of genetic, hormonal, immunological and
      environmental contributes to release the disease. Our objective was to describe
      and precise the epidemiological, clinical and immunological profile of this
      disease in Tunisia. METHOD: It is a retrospective study conducted by the Tunisian
      society of internal medicine during the period from January 1990 to December
      1999. All patients fulfilled at least four of the revised American Rheumatism
      Association's criteria for SLE. RESULTS: Two hundred and ninety-five SLE have
      been examined (271 women, 24 men). The most frequent clinical manifestations
      were: articular 90%, malar rash 62%, photosensitivity 46%, seritis 32% and
      glomerulonephritis 56%, dominated by WHO class III and IV: 60 cases (renal biopsy
      was performed in 95 patients). Neurological features were observed in 14.5%. The
      abnormal laboratory findings were leucocytopenia 45%, lymphopenia 47%,
      thrombocytopenia 16% and hemolytic anemia in 6.7%. Antinuclear antibodies, anti
      ds DNA and anti-Sm were at 92%, 74% and 57%, respectively. Eighty-three percent
      of patients were treated by steroids, and in 52 cases (18%), we added
      immunosuppressive drugs. Two hundred and eighteen patients were followed up with
      a mean follow-up duration of 51 months. Twenty-eight percent were in complete
      remission and in 60%, the SLE was active. In contrast, death occurred in 29
      cases. CONCLUSION: Our study confirmed the clinical polymorphism of SLE, the
      great similarity with other studies apart the world, the gravity of renal and
      cardiac features and the infectious complications induced by corticosteroids.

PMID- 14656637
TI  - [Tumor necrosis factor receptor superfamily 1A-associated periodic syndrome
      (TRAPS)].
AB  - PURPOSE: Tumor necrosis factor receptor superfamily 1A associated periodic
      syndrome (TRAPS) belongs to the group of hereditary fever syndromes, also called
      hereditary auto-inflammatory syndromes. CURRENT KNOWLEDGE AND KEY POINTS: The
      diagnosis of TRAPS should be evoked in presence of the following clinical signs,
      whatever the population of the affected patients. TRAPS acute inflammatory
      access, of 1 to 3 weeks' duration, is characterised by the presence of fever,
      abdominal pain, myalgias, various types of skin rash including erysepela-like
      erythema. Long term inflammatory response can lead to AA amyloidosis. Genetic
      testing will confirm the diagnosis when showing a mutation in the extracellular
      part of the TNFRSF1A receptor. Therapeutic management of TRAPS is not definitely
      established. Daily colchicine does not seem to prevent efficiently inflammatory
      attacks. Corticosteroids, in contrast can attenuate the intensity and diminish
      the duration of attacks. FUTURE PROSPECTS AND PROJECTS: The value of biological
      agents that inhibits TNF action is not yet completely determined in TRAPS.
      Mechanisms of the disease are not yet elucidated. In some families with specific
      mutations, a relative soluble TNF receptor deficiency has been found in the
      plasma. However this mechanism does not account for what is observed in other
      kindreds.

PMID- 14656638
TI  - [Nucleoside analogues resistance in the treatment of chronic hepatitis B virus
      infection].
AB  - SUBJECT: Chronic hepatitis B virus (HBV) infection is usually treated by
      interferon alpha. However, a sustained response after stopping treatment is only
      obtained in 30% of patients. ACTUALITY: New therapeutic nucleoside analogs have
      been developed, i.e. lamivudine, famciclovir, adefovir, entecavir, clevudine.
      However, as in HIV infection, clearance of the original hepatitis B virus with
      emergence of distinct resistant mutants have been observed during or after
      treatment with most nucleoside analogs. In this review, the underlying mechanisms
      of resistance and the characterisation of HBV mutants are described to optimize
      the best therapeutic regimen. PERSPECTIVES: Treatment of chronic HBV infection,
      as most of other chronic viral infection, should be based on combination therapy
      with a special search for the appearance of HBV mutant resistant.

PMID- 14656639
TI  - [Chronic severe uveitis: classification, search for etiology and therapeutic
      approach].
AB  - PURPOSE: Severe chronic and refractory uveitis is a major diagnostic and
      therapeutic challenge for ophthalmologists and internists. Molecular tools, such
      as PCR but also new imaging techniques, have significantly changed the diagnostic
      approach during the last 10 years. Presumed and empirical diagnosis should be
      excluded in the face of atypical clinical presentations. CURRENT KNOWLEDGE AND
      KEY POINTS: A retrospective study based on 927 consecutive patients presenting
      with severe uveitis between 1991-1996, has recently defined the epidemiological
      characteristics and the visual outcome of this group of patients. An associated
      condition was determined in 67.5% of cases, divided in 4 different subgroups:
      infectious uveitis; uveitis associated with a systemic disease; eye-limited,
      presumed immune-mediated disorder and idiopathic eye-limited disorder. The
      management of patients with sight-threatening forms of uveitis is efficiently
      performed in collaboration with internists and depends on a complete diagnostic
      procedure and a well-adapted treatment. FUTURE PROSPECTS AND PROJECTS: Extensive
      work-up is mandatory when the therapeutic response seems atypical with resistance
      to corticosteroids and classical immunosuppressive drugs. Infectious uveitis
      should be excluded in severe and intractable forms of uveitis. Thereafter, new
      therapeutic strategies based on type I interferon and anti-TNF molecules can be
      proposed in order to decrease the potential risk of blindness in this young group
      of patients.

PMID- 14656640
TI  - [Collections of human biological resources for research purposes: from
      regulations to the need of a guide of good collection practices].
AB  - PURPOSE: In France, collections of human biological resources are regulated by
      the "Bioethics Law", currently in revision. Hence, we analyse the regulatory and
      ethical issues of these practices in the context of scientific research. The
      ultimate aim of such collections is to improve biological and medical knowledge.
      CURRENT KNOWLEDGE AND KEY POINTS: We think that the French regulatory system is
      quite complicated and non-explicit for "collection holders". The multiplicity of
      legal texts concerning this activity has made their application difficult,
      especially in the absence of application decrees. The project amending the actual
      law has clarified the legal status of collections but it did not shed light on
      the status of human body detached parts. Furthermore, the text is still very far
      from the international bioethical recommendations, and does not reflect the
      actual collection's implementation. FUTURE PROSPECTS AND PROJECTS: The
      establishment of a guideline of Good Collection Practices, based on clear
      principles, should help to simplify the situation, especially when it is imbedded
      in the regulation and linked to control procedures. It would allow a balance
      between collective interests and the protection of individuals, taking into
      account of the international highly competitive scientific and economical
      constraints. The major issue is to preserve and to perpetuate the existing and
      future collections because of their precious value as an important tool for
      biomedical knowledge. The efficiency of a regulation depends on its legibility
      and accessibility, two requirements that seem to determine the acceptance of the
      regulatory tool and its application allowing subsequently to reach fairness in
      proceedings.

PMID- 14656641
TI  - [Association of a pulmonary, breast and cerebral tuberculosis].
AB  - INTRODUCTION: The concomitant unexpected arrival of a breast tuberculosis and
      cerebral tuberculomas to a same immunocompetent patient has not been ever
      described in the literature. EXEGESIS: We report the case of an non-HIV-infected
      woman who presented a pulmonary, breast tuberculosis and intracranial
      tuberculomas. Investigation for acid-fast bacilli in sputum and cerebrospinal
      fluid was negative. The patient received an antituberculous therapy for 15
      months, which led to the disappearance of the cerebral lesions. CONCLUSION: Our
      case was particular by the affected organs, the absence of immunodeficiency and
      the favorable outcome.

PMID- 14656642
TI  - [Difficult diagnosis of fever of unknown origin related to an infraclinic
      liposarcoma: "small tumor and fever of unknown origin"].
AB  - INTRODUCTION: Palpation of soft tissues constitutes part of the physical
      examination when faced with a patient with fever of unknown origin. Our case
      highlights the difficulty of diagnosis when the tumor still remains impalpable
      ten months after onset of fever and severe biological inflammatory process.
      EXEGESIS: A 49-year-old woman was admitted for fever of unknown origin associated
      with important biological inflammatory process. In view of her past medical
      history of breast carcinoma, a search for a relapse was performed and remained
      negative. Despite multiple investigations and repeated physical examinations, no
      diagnosis was obtained. Finally, [18F] fluorodoexyglucose positron emission
      tomography led to a diagnosis showing a high fixation located in the right thigh,
      related to a myxoid liposarcoma after surgical resection. CONCLUSION: Dramatic
      regression of fever and biological inflammatory process after surgical treatment
      illustrates the concept of "small tumor and fever of unknown origin", an
      exceptional entity but which physicians should be aware of. The role of new
      technical imaging with [18F] fluorodoexyglucose positron emission tomography has
      however to be clarified in the evaluation of fever of unknown origin.

PMID- 14656643
TI  - [Neurological feature of Mediterranean spotted fever: a study of four cases].
AB  - BACKGROUND: Rickettsia conorii is the etiologic agent of Mediterranean spotted
      fever that is endemic in Mediterranean. EXEGESIS: We report four cases of serious
      form of Mediterranean spotted fever with neurological feature. Two of them 56 and
      62 years old had meningoencephalitis. Two others had cerebellitis, they are aged
      43 and 56. The course has been favourable with ciprofloxacin. CONCLUSION: It is a
      benign well-known illness in spite of apparition of severe visceral
      complications, which can drag the death in 2.5% of cases. Neurological feature is
      more frequent and present in 28% of cases. Precocious treatment prevents this
      unfavourable evolution.

PMID- 14656644
TI  - [Bone marrow reconversion and magnetic resonance imaging: case report].
AB  - INTRODUCTION: Bone marrow is divided into red marrow mainly constituted of
      hemopoietic cells and fatty yellow marrow. In some situations, yellow marrow may
      be converted into red marrow and this process is called marrow reconversion.
      Magnetic resonance imaging may be misleading with an invading bone marrow
      neoplastic process. EXEGESIS: We report a patient with non-Hodgkin's lymphoma
      with vertebral invasion. Clinical features at presentation were misleading with
      lower limbs migratory pain suggestive of inflammatory myositis. An MRI study of
      thigh muscles revealed femoral nodular lesions suggestive of bone marrow
      reconversion. CONCLUSION: Bone marrow reconversion is a physiologic and
      reversible process. Awareness of its radiographic features may help to avoid a
      diagnostic biopsy procedure.

PMID- 14656645
TI  - [Pseudo-tumor of the shoulder].

PMID- 14656646
TI  - [Infiltration of the thyroid gland by Langerhans' cell histiocytosis: in adult
      "case report"].

PMID- 14656647
TI  - [3rd C1 Inhibitor Deficiency Workshop, Budapest, May 2003].

PMID- 14656648
TI  - [Parkinsonian syndrome during the systemic lupus erythematosus: a case report].

PMID- 14656649
TI  - [3rd International Symposium on Pulmonary Hypertension. Venezia, Italia, 23-25
      June 2003].

PMID- 14656651
TI  - [Contiguous Pseudomonas aeruginosa sacro-iliitis].

PMID- 14656650
TI  - [Hepatitis related to amoxicillin or levofloxacin: a case report].

PMID- 14656652
TI  - p63 gene analysis in Mexican patients with syndromic and non-syndromic
      ectrodactyly.
AB  - Ectrodactyly is a congenital limb malformation that involves a central reduction
      defect of the hands and/or feet which is frequently associated with other
      phenotypic abnormalities. The condition appears to be genetically heterogeneous
      and recently it has been demonstrated that mutations in the p63 gene, a homologue
      of the tumor suppressor gene p53, are the cause of at least four autosomal
      dominant genetic syndromes which feature ectrodactyly: ectrodactyly, ectodermal
      dysplasia, and facial clefting (EEC), split hand/split foot malformation (SHFM),
      limb-mammary syndrome (LMS), and acro-dermato-ungual-lacrimal-tooth syndrome
      (ADULT). In this study, genetic analysis of the p63 gene in a group of 13
      patients with ectrodactyly (syndromic and isolated) was performed. Four patients
      with syndromic ectrodactyly had p63 heterozygous point mutations that affect the
      DNA binding domain of the protein. One of these subjects exhibited the typical
      features of EEC syndrome as well as ankyloblepharon being, to our knowledge, the
      first case combining these traits. This finding supports the view of a clinical
      overlap in this group of autosomal dominant syndromes caused by p63 mutations and
      demonstrates that there are exceptions in the previously established p63 genotype
      phenotype correlation.

PMID- 14656654
TI  - NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis.
AB  - In this study we investigated the effect of NF-kB signaling blockade on
      polymethylmethacrylate (PMMA) particle-induced osteoclastogenesis in vitro. We
      first established effective blockade of NF-kB activity as tested by
      electrophoretic mobility shift assays (EMSA). Particle-induced NF-kB activation
      in murine osteoclast precursor cells (CSF-1-dependent bone marrow macrophages)
      was markedly reduced by co-treatment of the cells with the NF-kB inhibitors N
      tosyl-L-phenylalanine chloromethyl ketone (TPCK) and Calpain Inhibitor I (CPI).
      This inhibition of NF-kB activity was associated with blockade of p50 NF-kB
      subunit nuclear translocation. We then established a direct NF-kB inhibition
      approach by utilizing a TAT-bound, mutant IkB (TAT:IkB(46-317)), and demonstrated
      an inhibitory effect evidenced by decreased NF-kB DNA binding activity. Having
      established that these strategies (TPCK, CPI, TAT: IkB(46-317)) effectively block
      NF-kB activation, we next investigated the effect of these agents on particle
      stimulated osteoclast formation. PMMA particle stimulation of mature osteoclast
      formation from RANKL-primed osteoclast precursor cells was blocked by all three
      inhibitors. To further test the efficacy of NF-kB blockade, experiments were
      performed with the TAT:IkB(46-317) mutant peptide in whole bone marrow cultures
      that contain supporting stromal cells. Again, this inhibitor efficiently blocked
      particle-induced osteoclastogenesis. Thus, we have shown that pharmaceutical and
      molecular blockade of NF-kB activation inhibits PMMA particle-directed
      osteoclastogenesis in vitro.

PMID- 14656653
TI  - PGE2 and IL-6 production by fibroblasts in response to titanium wear debris
      particles is mediated through a Cox-2 dependent pathway.
AB  - Aseptic loosening of orthopaedic implants is precipitated by wear debris-induced
      osteolysis. Central to this process are the pro-inflammatory mediators that are
      produced in response to wear by the fibroblastic cells, which comprise the
      majority of periprosthetic membranes. Since this pro-inflammatory cascade is
      mediated by a plethora of factors with redundant functions, it is imperative to
      establish a hierarchy. Two well-known fibroblast derived pro-inflammatory factors
      that stimulate wear debris-induced osteoclastic resorption are prostaglandin E2
      (PGE2) and IL-6. However, their relationship to each other in this process is
      poorly defined. Here we show immunohistochemistry of retrieval membranes
      indicating that COX-2 is the principal cyclooxygenase responsible for PGE2
      production in fibroblasts around failed implants. We also performed in vitro
      experiments with fibroblasts derived from wild-type (WT), COX-1 (-/-) and COX-2 (
      /-) mice, which demonstrated that COX-2 is required for Ti wear debris-induced
      PGE2 production. Interestingly, COX-2 was also required for IL-6 production in
      these assays, which could be rescued by the addition of exogenous PGE2 (10(-6)
      M). Pharmacology studies that utilized the COX-1 selective inhibitor SC 560, the
      COX-2 selective inhibitor celecoxib, and the nonselective COX inhibitor
      indomethacin confirmed these results. Taken together, these results indicate that
      selective inhibition of prostaglandin signaling could favorably impact aseptic
      loosening beyond its direct effects on PGE2 synthesis, in that it inhibits
      downstream pro-inflammatory/pro-osteoclastic cytokine production.

PMID- 14656655
TI  - Erythromycin inhibits wear debris-induced osteoclastogenesis by modulation of
      murine macrophage NF-kappaB activity.
AB  - Activation of nuclear factor kappa B (NF-kappaB) signaling in response to cell
      stimulation by wear debris may be critical in the pathogenesis of aseptic
      loosening. Erythromycin (EM), a macrolide antibiotic, has been shown to
      effectively suppress some types of inflammatory reactions. In this study, we
      examined the effect of EM on wear debris-induced osteoclastic bone resorption in
      vitro. EM inhibited Ca+ release from neonatal calvaria co-cultured with
      conditioned medium from mouse RAW264.7 macrophages activated by wear debris.
      Inhibition of Ca+ release was associated with a decreased number of tartrate
      resistant acid phosphatase (TRAP)-positive cells in cultured bones. To
      investigate the mechanism whereby EM inhibits bone-resorption, RAW cells were
      incubated with wear debris in the presence EM. Real time RT-CR analysis revealed
      that EM (5 microg/ml) significantly inhibited mRNA expression of NF-kappaB,
      cathepsin K (CPK), IL-1beta and TNFalpha, but not RANK in RAW cells stimulated
      with wear debris. Furthermore, electrophoretic mobility-shift assay showed that
      EM (0.2 microg-5 microg/ml) could reduce DNA-binding activity of NF-kappaB in RAW
      cells stimulated with wear debris. The inhibition of inflammatory
      osteoclastogenesis by EM treatment was further confirmed by an osteoclast (OC)
      formation assay using primary cultures of mouse bone marrow progenitor cells
      stimulated with macrophage colony-stimulating factor and RANK ligand (RANKL). EM
      treatment (5 microg/ml) resulted in more than 70% reduction in multinucleated OC
      formation and 50% reduction of TRAP+ cells by bone marrow progenitor cells. Our
      findings support that EM suppresses wear debris-induced osteoclastic bone
      resorption by, at least, down-regulation of NF-kappaB signaling pathway. It
      appears that EM represents a potential therapeutic candidate for the treatment
      and prevention of aseptic loosening.

PMID- 14656657
TI  - Adhesion of Staphylococcus to orthopaedic metals, an in vivo study.
AB  - This study describes a new model of biofilm study in rabbits. The primary focus
      of this study was to assess biofilm adhesion to orthopaedic metals in their first
      48 h in a femoral intramedullary implantation model. Two previous inoculation
      methods i.e. that of pre- and direct inoculation were studied with two bacterial
      isolates namely Staphylococcus aureus and epidermidis, on titanium and stainless
      steel metallic implants. A method of sonication and log dilution/plating was used
      to assess biofilm bacteria adhering to implants. Silver coated metals were then
      compared with their respective control metals in the new model. The direct
      inoculation model gave larger and more reproducible biofilm adhesion to implanted
      metals. Staphylococcus epidermidis shows lower adhesion ability to metals, and
      biofilms adhere in greater numbers to stainless steel over titanium. Silver
      coated metals show no statistical difference over control metals when exposed to
      orthopaedic biofilms.

PMID- 14656656
TI  - The effects of patient age on human osteoblasts' response to Ti-6Al-4V implants
      in vitro.
AB  - Osseointegrated implants are a common therapy for the elderly population as
      lifespan increases. Understanding the effects of age and sex on osseointegration
      is important for successful implant therapy. Therefore, the response of primary
      human osteoblasts (HOB) to implant materials was studied. HOBs were obtained by
      outgrowth of cells from bone from orthopaedic procedures and categorized as Young
      (Y), <15; Middle (M), 30-50; and Old (O), >60 years old. Initially the HOB
      phenotype was determined on tissue culture plastic. Alkaline phosphatase (ALP)
      staining and activity were significantly increased in HOBs from older patients.
      Message levels of type I collagen (COL), bone sialoprotein (BSP) and ALP were
      significantly higher (from 2.3- to 3.8-fold) in Y subjects compared to M and O
      patients at 2 weeks. Studies of the response of HOBs to implant materials were
      undertaken using Ti-6Al-4V disks prepared in a manner similar to orthopaedic
      implants. A 1.4-fold (p<0.05) increase in cell attachment was found in HOBs from
      Y compared with O in female subjects but not in male subjects. Cell proliferation
      at 24 h was not significantly different by age or sex, nor was DNA content
      different at 2 and 4 weeks. Mineralization in HOB-implant cultures was 2.3-fold
      higher in Y than in O, and 1.7-fold higher in Y compared to M HOBs from female
      but not male subjects at 4 weeks. Northern blot and RT-PCR analysis at 2 weeks of
      culture showed significantly higher levels (1.6-2.3-fold) of COL, BSP, and
      osteocalcin (OC) mRNAs in Y HOBs compared to M and O HOBs from female subjects.
      We conclude that human osteoblasts from older female patients have a decreased
      ability to form bone on implants.

PMID- 14656658
TI  - The effect of total hip arthroplasty surgical approach on gait.
AB  - This study examined the effect of the surgical approach used in total hip
      arthroplasty (THA) on gait mechanics six months following surgery. Quantitative
      gait analysis was performed on 29 subjects: 10 anterolateral (A-L) and 10
      posterolateral (P-L) THA patients and nine able-bodied, velocity-matched
      subjects. Discriminant function analysis was used to determine the distinction of
      the groups with respect to sagittal plane hip range of motion, index of symmetry,
      trunk inclination, pelvic drop, hip abduction, and foot progression angles. The A
      L group had the largest trunk inclination (3.0+/-2.4 degrees) and the smallest
      hip range of motion (34.0+/-7.4 degrees). Both THA groups demonstrated greater
      asymmetry as expressed by the smaller symmetry index (0.97+/-0.04 for A-L and
      0.98+/-0.05 for the P-L) than the able-bodied group (0.99+/-0.01). The
      classification procedure correctly classified 89% of the control group cases, 90%
      of the A-L cases, and 50% of the P-L cases. These results support the conclusion
      that six months following surgery, the gait of the majority (85%) of THA patients
      has not returned to normal. The A-L patients displayed distinct gait patterns,
      while a small percentage (30%) of the P-L patients demonstrated normal gait.
      While these differences are statistically significant, the clinical significance
      is unknown and linked to the duration that they persist.

PMID- 14656659
TI  - Long stemmed total knee arthroplasty with interlocking screws: a computational
      bone adaptation study.
AB  - The ability of an interlocking screw fixation technique to minimize bone loss
      related to stress shielding in the tibia was investigated and compared to the
      abilities of cement and press-fit fixation. Full bony ingrowth has been
      associated with greater stress shielding than partial ingrowth; therefore, the
      effect of intimate bonding of the stem to bone on subsequent bone loss was also
      studied. A damage- and disuse-based remodeling theory was coupled with a two
      dimensional finite element model of the tibia to predict changes in bone
      remodeling following long stemmed total knee arthroplasty (TKA) for four
      different fixation techniques (cement, press-fit, interlock with bony ingrowth,
      and interlock without bony ingrowth). Remodeling changes commenced with the model
      state variables--bone area fraction, mechanical stimulus, damage, and remodeling
      activity--at steady-state values predicted by the intact tibia simulation. After
      TKA and irrespective of fixation technique, the model predicted elevated
      remodeling due to disuse, in which more bone was removed than replenished. In
      regions below the tibial tray and along the cortices, the interlocking stem with
      full bony ingrowth and the cemented stem caused the least amount of bone loss. An
      interlocking stem with a smooth, matted finish did not reduce the bone loss
      associated with interlocking fixation.

PMID- 14656660
TI  - Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine
      model.
AB  - The purpose of the present study was to determine if recombinant human bone
      morphogenetic protein-2 (rhBMP-2) enhances bone ingrowth into porous-coated
      implants and gap healing around the implants. In the presence of a 3-mm gap
      between the implant and host bone, porous-coated implants were placed bilaterally
      for four weeks in the proximal humeri of skeletally mature, adult male dogs. In
      three treatment groups, the test implant was treated with HA/TCP and rhBMP-2 in
      buffer at a dose of 100 microg/implant (n=5), 400 microg/implant (n=6), or 800
      microg/implant (n=5) and placed in the left humerus. In these same animals, an
      internal control implant was treated only with HA/TCP and buffer and placed in
      the right humerus. These groups were compared with a previously reported external
      control group of seven animals in which no growth factor was delivered [J.
      Orthop. Res. 19 (2001) 85]. The BMP treated implants in the two lower dose groups
      had significantly more bone ingrowth than the external controls with the greatest
      effect in the 100 g/implant group (a 3.5-fold increase over the external control,
      p=0.008). All three dose groups had significantly more bone formation in the 3-mm
      gap surrounding the BMP treated implants than the external controls with the
      greatest effect in the 800 microg group (2.9-fold increase, p<0.001). Thus,
      application of rhBMP-2 to a porous-coated implant stimulated local bone ingrowth
      and gap healing. The enhancement of bone formation within the implant (bone
      ingrowth) was inversely related to dose.

PMID- 14656661
TI  - Evaluation of Ad-BMP-2 for enhancing fracture healing in an infected defect
      fracture rabbit model.
AB  - The objective of this study was to evaluate the use of adenoviral transfer of the
      BMP-2 gene (Ad-BMP-2) for enhancing healing in an infected defect fracture model.
      A femoral defect stabilized with plates and screws was surgically created in
      sixty-four skeletally mature New Zealand white rabbits. Experimental groups were:
      (1) non-infected Ad-luciferase (Ad-LUC, NONLUC), (2) non-infected Ad-BMP-2
      (NONBMP), (3) infected Ad-LUC (INFLUC), and (4) infected Ad-BMP-2 (INFBMP). A
      sclerosing agent was applied to the ends of the bone at surgery to facilitate the
      development of osteomyelitis. Fracture healing was evaluated radiographically and
      histologically. Data were analyzed using an ANOVA, with statistical significance
      set as p<0.05. Rabbits in the non-infected and infected groups that were treated
      with Ad-BMP-2 had earlier initial- and bridging-callus formation, and a higher
      overall external callus grade compared to rabbits in the Ad-LUC groups. Rabbits
      in the Ad-LUC groups had more defect ossification compared to rabbits in the Ad
      BMP-2 groups. There was a trend for rabbits in the Ad-BMP-2 group that were
      euthanized at 2 and 4 weeks after surgery to have more bone and cartilage
      compared to rabbits in the Ad-LUC group. The results of this study suggest that
      Ad-BMP-2 enhances the early stages of healing in an infected defect fracture. The
      results of our study were not as favorable as those reported in previous studies
      because animals healed by a large bridging callus and not by defect ossification.
      This could have been a result of the sclerosing agent, which may have damaged the
      cells in the defect.

PMID- 14656662
TI  - Induced membranes secrete growth factors including vascular and osteoinductive
      factors and could stimulate bone regeneration.
AB  - Based on a new concept, a procedure combining induced membranes and cancellous
      autografts allows the reconstruction of wide diaphyseal defects. In the first
      stage of this procedure, a cement spacer is inserted into the defect; the spacer
      is responsible for the formation of a pseudo-synovial membrane. In the second
      stage, the defect is reconstructed two months later by an autologous cancellous
      bone graft. The aim of this study was to evaluate the histological and
      biochemical characteristics of these membranes induced in rabbits. Histological
      studies carried out two, four, six, and eight weeks following implantation
      revealed a rich vascularization. Qualitative and quantitative immunochemistry
      showed production of growth factors (VEGF, TGFbeta1) and osteoinductive factors
      (BMP-2). Maximum BMP-2 production was obtained four weeks after the implantation,
      and, at this time, induced membranes favored human bone marrow stromal cell
      differentiation to the osteoblastic lineage. Should these results be confirmed in
      humans, bone reconstruction could be carried out earlier than previously thought
      and in better conditions than expected, the membrane playing the role of an in
      situ delivery system for growth and osteoinductive factors.

PMID- 14656663
TI  - Microcirculatory effects of pulsed electromagnetic fields.
AB  - PURPOSE: Pulsed electromagnetic fields (PEMF) are used clinically to expedite
      healing of fracture non-unions, however, the mechanism of action by which PEMF
      stimulation is effective is unknown. The current study examined the acute effects
      of PEMF stimulation on arteriolar microvessel diameters in the rat cremaster
      muscle. The study hypothesis was that PEMF would increase arteriolar diameters, a
      potential mechanism involved in the healing process. METHODS: Local PEMF
      stimulation/sham stimulation of 2 or 60 min duration was delivered to the
      cremaster muscle of anesthetized rats. Arteriolar diameters were measured before
      and after stimulation/sham stimulation using intravital microscopy. Systemic
      hemodynamics also were monitored during PEMF stimulation. RESULTS: Local PEMF
      stimulation produced significant (p<0.001) vasodilation, compared to pre
      stimulation values, in cremasteric arterioles in anesthetized rats (n=24). This
      dilation occurred after 2 min of stimulation (9% diameter increase) and after 1 h
      of stimulation (8.7% diameter increase). Rats receiving "sham" stimulation (n=15)
      demonstrated no statistically significant change in arteriolar diameter following
      either "sham" stimulation period. PEMF stimulation of the cremaster (n=4 rats)
      did not affect systemic arterial pressure or heart rate, nor was it associated
      with a change in tissue environmental temperature. CONCLUSIONS: These results
      support the hypothesis that local application of a specific PEMF waveform can
      elicit significant arteriolar vasodilation. Systemic hemodynamics and
      environmental temperature could not account for the observed microvascular
      responses.

PMID- 14656664
TI  - Distribution of in situ forces in the anterior cruciate ligament in response to
      rotatory loads.
AB  - The anterior cruciate ligament (ACL) can be anatomically divided into
      anteromedial (AM) and posterolateral (PL) bundles. Current ACL reconstruction
      techniques focus primarily on reproducing the AM bundle, but are insufficient in
      response to rotatory loads. The objective of this study was to determine the
      distribution of in situ force between the two bundles when the knee is subjected
      to anterior tibial and rotatory loads. Ten cadaveric knees (50+/-10 years) were
      tested using a robotic/universal force-moment sensor (UFS) testing system. Two
      external loading conditions were applied: a 134 N anterior tibial load at full
      knee extension and 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion
      and a combined rotatory load of 10 Nm valgus and 5 Nm internal tibial torque at
      15 degrees and 30 degrees of flexion. The resulting 6 degrees of freedom
      kinematics of the knee and the in situ forces in the ACL and its two bundles were
      determined. Under an anterior tibial load, the in situ force in the PL bundle was
      the highest at full extension (67+/-30 N) and decreased with increasing flexion.
      The in situ force in the AM bundle was lower than in the PL bundle at full
      extension, but increased with increasing flexion, reaching a maximum (90+/-17 N)
      at 60 degrees of flexion and then decreasing at 90 degrees. Under a combined
      rotatory load, the in situ force of the PL bundle was higher at 15 degrees (21+/
      11 N) and lower at 30 degrees of flexion (14+/-6 N). The in situ force in the AM
      bundle was similar at 15 degrees and 30 degrees of knee flexion (30+/-15 vs. 35+/
      16 N, respectively). Comparing these two external loading conditions demonstrated
      the importance of the PL bundle, especially when the knee is near full extension.
      These findings provide a better understanding of the function of the two bundles
      of the ACL and could serve as a basis for future considerations of surgical
      reconstruction in the replacement of the ACL.

PMID- 14656665
TI  - Kinematics of the knee at high flexion angles: an in vitro investigation.
AB  - Restoration of knee function after total knee, meniscus, or cruciate ligament
      surgery requires an understanding of knee behavior throughout the entire range of
      knee motion. However, little data are available regarding knee kinematics and
      kinetics at flexion angles greater than 120 degrees (high flexion). In this
      study, 13 cadaveric human knee specimens were tested using an in vitro robotic
      experimental setup. Tibial anteroposterior translation and internal-external
      rotation were measured along the passive path and under simulated muscle loading
      from full extension to 150 degrees of flexion. Anterior tibial translation was
      observed in the unloaded passive path throughout, with a peak of 31.2+/-13.2 mm
      at 150 degrees. Internal tibial rotation increased with flexion to 150 degrees on
      the passive path to a maximum of 11.1+/-6.7 degrees. The simulated muscle loads
      affected tibial translation and rotation between full extension and 120 degrees
      of knee flexion. Interestingly, at high flexion, the application of muscle loads
      had little effect on tibial translation and rotation when compared to values at
      120 degrees. The kinematic behavior of the knee at 150 degrees was markedly
      different from that measured at other flexion angles. Muscle loads appear to play
      a minimal role in influencing tibial translation and rotation at maximal flexion.
      The results imply that the knee is highly constrained at high flexion, which
      could be due in part to compression of the posterior soft tissues (posterior
      capsule, menisci, muscle, fat, and skin) between the tibia and the femur.

PMID- 14656666
TI  - Strength and voluntary activation of the quadriceps femoris muscle at different
      severities of osteoarthritic knee joint damage.
AB  - OBJECTIVE: Improvements of quadriceps motor deficits represent a major
      therapeutical target in knee osteoarthritis (OA). In the present study, we
      investigated changes in quadriceps function at different stages of osteoarthritic
      cartilage damage. METHODS: Measurements of quadriceps voluntary activation (VA)
      and maximum voluntary contraction (MVC) were performed by a twitch interpolation
      technique and the total muscular capacity (TMC) was calculated as the ratio of
      MVC and VA. We assessed 68 patients (56.7+/-9.5 years) with stage II and 154
      patients (65.6+/-6.0 years) with stage IV chondropathy. As controls, we used 85
      age related healthy subjects (58.1+/-8.7 years). RESULTS: While TMC was
      significantly lower in stage IV (90.6+/-43.7 Nm) than in stage II chondropathy
      (109.6+/-51.0) there were no differences in the MVCs between both groups.
      Quadriceps VA was even higher in stage IV (77.2+/-13.2%) than in stage II
      chondropathy (70.8+/-16.0%). In the controls, MVC, VA and TMC were significantly
      higher than in both OA groups. CONCLUSION: We assume that a decrease of TMC might
      occur within the course of OA and, in consequence, VA increases to maintain
      quadriceps MVC.

PMID- 14656667
TI  - Anatomical analysis of the femoral condyle in normal and osteoarthritic knees.
AB  - It is important to understand anatomical feature of the distal femoral condyle
      for treatment of osteoarthritic knees. Detailed measurement of the femoral
      condyle geometry, however, has not been available in osteoarthritic knees
      including valgus deformity. This study evaluated femoral condyle geometry in 30
      normal knees, 30 osteoarthritic knees with varus deformity, and 30 osteoarthritic
      knees with valgus deformity using radiographs and magnetic resonance imaging
      (MRI). In radiographic analysis in the coronal plane, the femoral joint angle
      (lateral angle between the femoral anatomic axis and a tangent to femoral
      condyles) was 83.3 degrees in the normal knees, 83.8 degrees in the varus knees,
      and 80.7 degrees in the valgus knees. In MRI analysis in the axial plane, the
      posterior condylar tangent showed 6.4 degrees of internal rotation relative to
      the transepicondylar axis in the normal knees, 6.1 degrees in the varus knees,
      and 11.5 degrees in the valgus knees. These results suggested that there was no
      hypoplasia of the medial condyle in the varus knees, but the lateral condyle in
      the valgus knees was severely distorted. Surgeons should take this deformity of
      the lateral femoral condyle into account when total knee arthroplasty is
      performed for a valgus knee.

PMID- 14656669
TI  - The nature of anterior knee pain following injection of hypertonic saline into
      the infrapatellar fat pad.
AB  - The infrapatellar fat pad has been implicated as a possible source of anterior
      knee pain. This study examined the nature, distribution and time-course of
      experimentally induced pain in the infrapatellar fat pad. Hypertonic saline (5%)
      was injected into the medial fat pad of 11 healthy individuals with no history of
      knee pain. Severity of pain was assessed at rest and during activity using an 11
      point numerical rating scale (NRS) at regular intervals over 15-30 min following
      injection. Participants described the size of the pain region from a series of
      different sized circles while the area and type of pain was established from a
      body chart and the McGill pain questionnaire. The effect of pain on temperature
      pain threshold and sensory thresholds of the anterior knee was assessed.
      Participants generally reported a deep aching pain that peaked in severity around
      3 min and gradually declined over 15 min. Pain levels were not altered by
      clinical manoeuvres designed to impinge the fat pad. The size of the pain region
      was related to pain intensity. Pain was most commonly felt in the region of the
      fat pad medial to the patella, although some individuals reported proximal
      referred pain as far as the groin region. Thermal and sensory thresholds were not
      altered at a region close to the injection site during the experimental pain.
      These results suggest that nociceptive stimulation of the infrapatellar fat pad
      may cause anterior knee pain that is not necessarily confined locally
      particularly if pain is severe. This has implications for the investigation of
      pathological structures in patients presenting clinically with anterior knee pain
      and provides an experimental model of anterior knee pain.

PMID- 14656668
TI  - Quadriceps femoris muscle weakness and activation failure in patients with
      symptomatic knee osteoarthritis.
AB  - PURPOSE: Quadriceps weakness is common in patients with knee osteoarthritis (OA),
      and has been attributed to failure of voluntary activation. Methodological
      differences may have contributed to previous reports of extensive failure of
      voluntary activation in patients with osteoarthritis. The purpose of this study
      was to determine the extent of quadriceps muscle weakness and activation failure
      in middle aged patients with symptomatic medial knee osteoarthritis using maximum
      voluntary isometric contractions (MVIC) and a burst superimposition technique.
      METHODS: Measurements of quadriceps MVIC and extent of voluntary activation were
      made in 12 subjects with knee OA and 12 similarly aged uninjured subjects.
      Voluntary activation was tested by superimposing a train of electrical
      stimulation on a maximal effort volitional contraction of the quadriceps muscle.
      RESULTS: The group of subjects with knee OA had significantly less quadriceps
      strength relative to body mass index (BMI) than the group of control subjects
      (p=0.010). No difference in voluntary activation was observed (p=0.233), however,
      50% of the OA group, and only 25% of the control group failed to fully activate
      the quadriceps. DISCUSSION: The finding of quadriceps weakness is consistent with
      past literature. Providing adequate instruction, feedback, and several attempts
      to maximally contract the muscle likely yielded greater volitional activation
      (thus less activation failure) than had been reported previously. This finding
      has implications for the rehabilitation of weakened quadriceps in patients with
      knee osteoarthritis.

PMID- 14656670
TI  - Indentation properties of growing femoral head following ischemic necrosis.
AB  - Little is known about the mechanical properties of the growing femoral head as it
      develops deformity following ischemic injury. The purpose of this study was to
      determine the indentation stiffness of growing femoral head following ischemic
      injury and to correlate the changes in stiffness with radiographic and
      histopathologic changes in the femoral head as it develops deformity. Following
      the induction of ischemia in 24 piglets, indentation testing of whole femoral
      heads was performed at 2, 4, and 8 weeks, as well as on femoral heads from eight
      sham operated animals. At 2 weeks, a 52% reduction of indentation stiffness was
      observed in the infarcted femoral heads compared to the control heads (p=0.004).
      The bony epiphyses in infarcted femoral heads were smaller due to growth arrest
      but they were not deformed. Histologically, no evidence of repair was seen. At 4
      and 8 weeks, the indentation stiffness in the infarcted femoral heads was reduced
      by 75% (p<0.000001) and 72% (p=0.001) respectively compared to the control heads.
      Variable degree of femoral head deformity and repair was observed at 4 weeks.
      Severe deformity with extensive revascularization and repair were observed at 8
      weeks. Although epiphyseal cartilage was thickened on the infarcted femoral heads
      only a weak correlation was found between the increase in the cartilage thickness
      and the decrease in the indentation stiffness (R(2)=0.55). These results indicate
      that the indentation properties of growing femoral head were significantly
      affected by ischemic injury, prior to the presence of repair process and
      deformity. A further decrease in the indentation stiffness was concomitant with
      repair of the infarcted head. These findings suggest that a reduction in the
      mechanical properties of the infarcted femoral head include both a cartilage and
      a bony component, which cannot be differentiated at this point. The study
      validates early institution of treatments that are aimed at limiting the
      mechanical loading of the affected hip. The study also suggests that in order to
      minimize the mechanical compromise of the infarcted femoral head, early
      institution of treatments aimed at stimulating new bone formation and retarding
      osteoclastic bone resorption may be beneficial.

PMID- 14656672
TI  - Chondrocyte apoptosis induced by collagen degradation: inhibition by caspase
      inhibitors and IGF-1.
AB  - The main objective of this study was to test the effectiveness of candidate
      apoptosis inhibitors in limiting chondrocyte apoptosis induced by collagen
      degradation. Primary human chondrocytes were isolated from normal articular
      cartilage and grown in monolayer culture. Collagenase was added to the cells in
      the presence and absence of caspase inhibitors and insulin like growth factor
      (IGF)-1. The amount of chondrocyte apoptosis was measured using an enzyme linked
      immunosorbent assay for nucleosomes, a specific and quantitative measure of
      apoptosis. Chondrocyte apoptosis was induced by collagenase treatment in both a
      time and dose dependent manner. The non-selective caspase inhibitor Z-VAD, the
      caspase-3 selective inhibitor Z-DEVD, and the growth factor insulin like growth
      factor (IGF)-1 inhibited chondrocyte apoptosis induced by collagenase treatment.
      The caspase-1 selective inhibitor Z-YVAD also blocked chondrocyte apoptosis under
      these conditions, in contrast to previous studies where caspase-1 inhibition
      failed to block apoptosis induced by agents such as the topoisomerase inhibitor
      camptothecin. These data demonstrate that the response of chondrocytes to caspase
      inhibition may be dependent upon the specific stimulus that initiates apoptosis.
      Furthermore, these findings suggest that multiple pathways involving both the
      initiation and execution of programmed cell death are potential targets for
      chondrocyte apoptosis inhibition therapy.

PMID- 14656671
TI  - The role of the cytoskeleton in the viscoelastic properties of human articular
      chondrocytes.
AB  - Biomechanical factors are believed to play an important role in regulating the
      metabolic activity of chondrocytes in articular cartilage. Previous studies
      suggest that cytoskeletal proteins such as actin, vimentin, and tubulin influence
      cellular mechanical properties, and may therefore influence the mechanical
      interactions between the chondrocyte and the surrounding tissue matrix. In this
      study, we investigated the role of specific cytoskeletal components on the
      mechanical properties of individual chondrocytes isolated from normal or
      osteoarthritic hip articular cartilage. Chondrocytes were exposed to a range of
      concentrations of chemical agents that disrupt the primary cytoskeletal elements
      (cytochalasin D for F-actin microfilaments, acrylamide for vimentin intermediate
      filaments, and colchicine for microtubules). Chondrocyte mechanical properties
      were determined using the micropipette aspiration technique coupled with a
      viscoelastic solid model of the cell. Chondrocyte stiffness (elastic modulus) was
      significantly increased with osteoarthritis. With increasing cytochalasin D
      treatment, chondrocyte stiffness decreased by up to 90% and apparent viscosity
      decreased by up to 80%. The effect of cytochalasin D was greater on normal
      chondrocytes than those isolated from osteoarthritic cartilage. Treatment with
      acrylamide also decreased the moduli and viscosity, but only at the highest
      concentration tested. No consistent changes in cell mechanical properties were
      observed with colchicine treatment. These findings suggest that microfilaments
      and possibly intermediate filaments provide the viscoelastic properties of the
      chondrocyte, and changes in the structure and properties of these cytoskeletal
      elements may reflect changes in the chondrocyte with osteoarthritis.

PMID- 14656673
TI  - Cartilage injury by ramp compression near the gel diffusion rate.
AB  - The mechanics of cartilage injuries have implications for repair strategies. We
      examined the role of strain rate in cartilage injury under compression near the
      "gel diffusion" rate (the inherent tissue mechanical relaxation rate). Bovine
      osteochondral explant disks were subjected to one radially unconfined axial
      compression at approximately 0.1, 1, 10, 100, or 1000 times the gel diffusion
      rate to a peak stress of 3.5, 7, or 14 MPa. Effects were monitored in terms of
      axial strain, changes in water content, superficial cracks, chondrocyte
      viability, and proteoglycan release. Injury worsened monotonically with peak
      stress, but varied substantially with strain rate. High strain rates resulted in
      significant matrix fluid pressurization and impact-like surface cracking with
      cell death near the superficial zone. Below the gel diffusion rate, cells died
      throughout the tissue depth during extensive matrix consolidation without cracks.
      At approximately the gel diffusion rate, no measurable injury occurred, even for
      peak stresses of 14 MPa and axial compressive strains near 0.8. The gel diffusion
      rate therefore represented a threshold separating different biomechanical regimes
      of injury, but at which cartilage was relatively "safe" from injury. Findings may
      help identify strategies for prevention and treatment of cartilage injury and
      suggest loading guidelines for tissue engineering.

PMID- 14656674
TI  - Intramatrix events during cryopreservation of porcine articular cartilage using
      rapid cooling.
AB  - Cryopreservation of articular cartilage may improve long-term transplantation
      results if cell and matrix integrity can be maintained. This study examined
      intramatrix events in intact porcine articular cartilage that occurred during a
      rapid-cooling technique with various concentrations of dimethyl sulfoxide (DMSO)
      (1, 3, 5, 6 and 7 M). Thermocouples were inserted into the solution and in the
      cartilage matrix to record the temperature during rapid cooling. In addition,
      scanning electron microscopy of freeze-substituted samples was performed and
      quantitatively evaluated for the areas representing ice in the matrix. The
      results of this study showed that low concentrations of DMSO resulted in the
      largest temperature gradient between the matrix and the surrounding solution,
      which occurred near the freezing point of the cryoprotectant solution. At higher
      concentrations of DMSO, the peak temperature gradient occurred near the glass
      transition temperature. The temperature measurements suggested that a significant
      amount of ice formed within the matrix at lower DMSO concentrations. At higher
      DMSO concentrations that resulted in vitrification of the external solution,
      there was evidence of some ice in the matrix. The scanning electron micrographs
      demonstrated significantly more matrix disruption (likely due to ice formation)
      (P<0.02) in the lower DMSO concentrations (1 and 5 M) while the 6 M DMSO
      concentration demonstrated minimal matrix disruption. Cryopreservation of
      articular cartilage with a rapid-cooling technique and high concentrations of
      DMSO resulted in partial vitrification of the matrix and significantly less
      matrix disruption. It appears that successful cryopreservation of viability and
      function in articular cartilage will require high concentrations of
      cryoprotectants and rapid cooling.

PMID- 14656675
TI  - A biomechanical study of lumbar spondylolysis based on a three-dimensional finite
      element method.
AB  - Biomechanical analyses under compression only, and for a combination of flexion,
      extension, rotation, and lateral bending were performed to evaluate the stress of
      the interarticular portion of the lumbar vertebra using a nonlinear three
      dimensional finite element method. A detailed three-dimensional L4-L5 motion
      segment model was developed that took into consideration the material
      nonlinearities of ligaments and annular fibers and the contact nonlinearities of
      facet joints. For a more accurate examination, the separation of cortical bone
      and cancellous bone for both posterior and anterior elements were also
      considered. The stress in the pars interarticularis was weakest under compression
      alone, but stronger under compression with lateral bending loading, with flexion,
      with rotation, and with extension. Under each loading condition, the region of
      the stress concentration was consistent with the separated region of the
      spondylolysis observed in clinical situations. Since the stress in the pars
      interarticularis was high under extension and rotation in particular, those
      loadings were suggested to be relatively high risk factors leading to
      spondylolysis.

PMID- 14656676
TI  - The compressive creep properties of normal and degenerated murine intervertebral
      discs.
AB  - Identifying mechanisms by which degeneration alters intervertebral disc material
      properties and biomechanical behavior is important for clarifying back pain risk
      factors as well as for evaluating the efficacy of novel interventions. Our goal
      was to quantify and characterize degeneration-dependent changes in the disc's
      response to compression using a previously established murine model of disc
      degeneration. We performed compressive creep tests on normal and degenerated
      murine intervertebral discs and parameterized the biomechanical response using a
      previously established fluid-transport model. Using a series of biochemical and
      histological assays, we sought to determine how biomechanical alterations were
      attributable to degeneration-related changes in tissue morphology. We observed
      that with moderate degeneration, discs lost height (mean+/-std. dev. of 0.44+/
      0.01 vs. 0.36+/-0.01 mm, p<0.0001), increased in proteoglycan content (31+/-4 vs.
      43+/-2 microg/ml of extract, p<0.0002), became less stiff (2.17+/-0.66 vs. 1.56+/
      0.44 MPa, p<0.053), and crept more. Model results suggested that the increased
      creep response was mainly due to a diminished strain-dependent nuclear swelling
      pressure. We also noted that the model-derived tissue properties varied with the
      applied load magnitude for both normal and degenerated discs. Overall, our data
      demonstrate that architectural remodeling stimulated by excessive loading
      diminishes the disc's ability to resist compression. These results are similar to
      degeneration-dependent changes reported for human discs.

PMID- 14656677
TI  - Pathology of lumbar nerve root compression. Part 1: Intraradicular inflammatory
      changes induced by mechanical compression.
AB  - STUDY DESIGN: This study is to investigate the intraradicular inflammation
      induced by mechanical compression using in vivo model. OBJECTIVES: The
      relationship between the intraradicular edema and nerve fiber degeneration
      induced by mechanical compression was determined in the nerve root. SUMMARY OF
      BACKGROUND DATA: Recently some studies reported that mechanical compression
      increased microvascular permeability of the endoneurial capillaries and resulted
      in an intraradicular inflammation. These changes may be an important factor of
      the pathogenesis of radiculopathy. However, the natural courses of the
      intraradicular inflammation after mechanical compression are still poorly
      understood. METHODS: In dogs, laminectomy was performed at L7 and the seventh
      nerve root was exposed to compression at 7.5 gram force (gf) clipping power. The
      animals were evaluated at 1 and 3 weeks after clipping. After the appropriate
      period of nerve root compression, Evans blue albumin (EBA) was injected
      intravenously. The nerve root sections were divided into two groups. The sections
      were used to investigate the status of the blood-nerve barrier function under the
      fluorescence microscope. The other sections were used for light and transmission
      electron microscopic study. RESULTS: After 1 and 3 weeks, intraradicular edema
      was observed not only at the site of compression but also in the peripheral zone
      of a compressed anterior root and in the central zone of a compressed posterior
      root. The evidence of active Wallerian degeneration was also seen in the area of
      intraradicular edema. In addition, the nerve roots showing Wallerian degeneration
      were infiltrated by inflammatory cells, such as macrophages and mast cells.
      CONCLUSIONS: Inflammatory reaction, such as Wallerian degeneration, breakdown of
      blood-nerve barrier and appearance of macrophage, may be deeply involved in
      radiculitis arising from mechanical compression, and these factors seem to be
      important in the manifestation of radiculopathy.

PMID- 14656678
TI  - Pathology of lumbar nerve root compression. Part 2: morphological and
      immunohistochemical changes of dorsal root ganglion.
AB  - STUDY DESIGN: This study is to investigate the changes of dorsal root ganglion
      (DRG) induced by mechanical compression using in vivo model. OBJECTIVES: The
      effect of axonal flow disturbance induced by nerve root compression was
      determined in DRG. SUMMARY OF BACKGROUND DATA: The dorsal root ganglion should
      not be overlooked when considering the mechanism of low back pain and sciatica,
      so it is important to understand the morphologic and functional changes that
      occur in primary sensory neurons of the dorsal root ganglion as a result of nerve
      root compression. However, few studies have looked at changes of neurons within
      the dorsal root ganglion caused by disturbance of axonal flow and the axon
      reaction as a result of mechanical compression of the dorsal root through which
      the central branches of the primary sensory nerves pass. METHODS: In mongrel
      dogs, the seventh lumbar nerve root was compressed for 24 h, one week, or three
      weeks using a clip with a pressure of 7.5 gf. Morphologic changes of the primary
      sensory neurons in the dorsal root ganglion secondary to the axon reaction were
      examined by light and electron microscopy. Changes of immunostaining for
      substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM)
      in the primary sensory neurons affected by central chromatolysis after nerve root
      compression were also examined. RESULTS: Light microscopy showed central
      chromatolysis of neurons in the dorsal root ganglion from one week after the
      start of compression. Electron microscopy of the affected neurons revealed
      movement of the nucleus to the cell periphery and the loss of rough endo-plasmic
      reticulum and mitochondria from the central region. Immunohistochemical studies
      showed a marked decrease of SP, CGRP, and SOM staining in small ganglion cells
      with central chromatolysis when compared with cells from control ganglia.
      CONCLUSION: It is important to be aware that in patients with nerve root
      compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction
      is not confined to degeneration at the site of compression, but also extends to
      the primary sensory neurons within the dorsal root ganglion as a result of the
      axon reaction. Patients with sensory disturbance should therefore be fully
      informed of the fact that these symptoms will not resolve immediately after
      surgery.

PMID- 14656679
TI  - Pre-degenerated nerve shows enhanced regeneration after incremental elongation in
      rats.
AB  - Following nerve degeneration, we investigated effects of linear elongation on
      subsequent nerve regeneration in a total of 92 Wistar rats (weight 380-430 g).
      The nerve was ligated at the midthigh and then elongated incrementally by a total
      of 15 mm by leg lengthening at a rate of 3 or 5 mm/day. Seven days after
      initiation of nerve elongation, the external fixator was removed and normal leg
      length was restored with internal fixation. Then a 10 mm nerve segment at the
      ligature site was excised, and the nerve was repaired with sutures (group D). At
      2, 4, 6, and 8 weeks after nerve suturing, we examined transverse semi-thin nerve
      sections compared with group I (severed and repaired after leg lengthening
      without a nerve ligature) and control group (severed and repaired without leg
      lengthening). After lengthening at 3 mm/day, nerve regeneration in group D was
      enhanced at 4 weeks. After lengthening at 5 mm/day, nerve regeneration in group D
      also was enhanced at 6 and 8 weeks. Pre-degenerated nerve showed better
      regeneration after suturing than intact nerve. Elongation holds promise as an
      alternative to nerve grafting in treatment of nerve injury.

PMID- 14656680
TI  - The effect of capsular tightening on humeral head translations.
AB  - Idiopathic or surgical tightening of the glenohumeral joint capsule may cause
      displacement of the humeral head relative to the glenoid fossa and favor the
      development of instability and/or osteoarthritis. In the present investigation
      the relative position of the humerus to the glenoid fossa was determined at the
      end of the ranges of eight different passive movements before and after selective
      capsular plication in eight cadaveric shoulders to study the effects of selective
      capsular plications on the kinematics of the shoulder. While the capsule was in
      its unaltered state, translation of the humeral head was 3.8 mm superiorly in
      abduction, 7.3 mm antero-superiorly in flexion. In internal rotation in 0
      degrees, 45 degrees and 90 degrees of abduction the head moved 6.1, 8.0 and 12.0
      mm antero-inferiorly. In external rotation at 0 degrees of abduction the
      translation was 0.9 mm antero-inferiorly, at 45 degrees and 90 degrees of
      abduction it was 4.3 and 5.6 mm postero-inferiorly, respectively. Plications of
      the anterior part of the capsule reproducibly and significantly either increased
      or decreased translations during flexion (up to 5.9 mm anteriorly and up to 3.8
      mm inferiorly), external rotation (up to 2.9 mm posteriorly and 1 mm inferiorly)
      and internal rotation (from 5.5 mm posteriorly to 2 mm anteriorly and up to 2.2
      mm superiorly). Posterior plications had only little effect on translations
      (mainly a decrease of anterior translation during flexion of 2.8 mm). CLINICAL
      RELEVANCE: The 'obligate' glenohumeral translations which occur towards the end
      of passive shoulder movements are altered in a reproducible fashion by tightening
      specific parts of the glenohumeral joint capsule, as often carried out in
      treatment of shoulder instability. These alterations of the kinematics of the
      glenohumeral joint may be relevant for the development of static subluxation and
      osteoarthitis as seen after too tight plication in the treatment of instability
      [Int. Orthop. (SICOT) 67-B (1985) 709; J. Bone Joint Surg. Am. 72 (1990) 1193; J.
      Bone Joint Surg. Am. 66-A (1984) 169; J. Bone Joint Surg. Am. 65 (1983) 456].

PMID- 14656681
TI  - Glenoid version and rotator cuff tears.
AB  - The purpose of this study was to determine the relationship between rotator cuff
      (RC) tear and the orientation of the glenoid. Ninety-six shoulders (94 patients)
      that underwent open RC repair were grouped according to the type of tear. We
      measured on MRI the acromio-glenoid angle (AG) and the supraspinatus fossa
      glenoid angle on the anterior-posterior (SGAP) and axial (SGAX) views. RC
      patients had a smaller AG angle (76+/-7 degrees vs. 86+/-10 degrees ) and a
      larger SGAP angle (112+/-6 degrees vs. 102+/-7 degrees ) compared to controls
      (p<0.001). We also found a highly significant difference (p<0.001) in glenoid
      version measured by SGAX between anterior cuff tears (-5+/-4 degrees ) and
      posterior cuff tears (3+/-3 degrees ). Furthermore, we identified an association
      between RC tear and the orientation of the glenoid relative to the axis of the
      supraspinatus fossa. Greater retroversion is predictive of an anterior cuff
      injury and greater anteversion is predictive of a posterior cuff injury.

PMID- 14656682
TI  - Electromyographic activity and strength during maximum isometric pronation and
      supination efforts in healthy adults.
AB  - There exists a lack of quantitative data in the literature related to the torque
      produced during axial forearm rotation and the electromyographic (EMG) activity
      of the muscles involved. Therefore, the purpose of this study was to compare the
      relative EMG activity of four forearm muscles during resisted forearm rotation. A
      custom-built device capable of measuring torque in the absence of grip was
      employed. Fourteen healthy volunteers performed maximum isometric voluntary
      contractions in five positions of axial forearm rotation for both pronation and
      supination. EMG data were collected simultaneously from the supinator, biceps,
      pronator quadratus (deep and superficial heads), and pronator teres muscles using
      fine-wire bipolar electrodes. Data were analyzed to determine the contributions
      of each muscle to pronation and supination torque over five positions of forearm
      rotation. In the absence of grip no significant difference was found between
      supination and pronation torque in neutral position. Supination torque generation
      was greater in the pronated forearm positions, and pronation torque was greater
      in the supinated positions (p<0.05). A root-mean-square EMG analysis verified the
      major contributions of the pronator teres and both heads of the pronator
      quadratus muscle to pronation torque, and supinator and biceps to supination
      torque. The deep head of the pronator quadratus was active during both pronation
      and supination, lending support to the theory that it may act primarily as a
      dynamic distal radioulnar joint stabilizer. This information may be helpful in
      upper extremity modeling, surgical treatments, and rehabilitation strategies.

PMID- 14656683
TI  - The use of porcine small intestinal submucosa to enhance the healing of the
      medial collateral ligament--a functional tissue engineering study in rabbits.
AB  - INTRODUCTION: Small intestinal submucosa (SIS) from porcine has been successfully
      used as a collagen scaffold for the repair of various tissues, including those of
      the human vascular, urogenital, and musculoskeletal systems. The objective of
      this study was to evaluate whether SIS can be used to enhance the healing process
      of a medial collateral ligament (MCL) with a gap injury in a rabbit model.
      METHODS: A 6 mm wide gap was surgically created in the right MCL of 20 skeletally
      mature, female New Zealand White rabbits. In 10 rabbits, a strip of SIS was
      sutured onto the two ends of the MCL, while for the other 10 animals their
      injured MCL remained untreated and served as a non-treated group. The left MCL of
      all animals was exposed and undermined serving as the sham-operated side. At 12
      weeks post-healing, eight hind limbs from each group were used for mechanical
      testing. The cross-sectional areas (CSA) of the MCLs were measured. The femur-MCL
      tibia complex (FMTC) was tensile tested to failure. The load-elongation curves
      representing the structural properties of the FMTC and the stress-strain curves
      representing the mechanical properties of the healing MCL were obtained. The
      remaining two animals from each group were prepared for histological evaluation.
      RESULTS: The CSA between the SIS-treated and non-treated groups were not
      significantly different (p>0.05). Both treatment groups appeared to increase by
      nearly 40% compared to the sham-operated side, although statistical significance
      was not found for the non-treated group (p>0.05). The stiffness of the FMTC from
      the SIS-treated group was 56% higher than the non-treated group (45.7+/-13.3 N/mm
      vs. 29.2+/-9.2 N/mm, respectively, p<0.05) and the ultimate load also nearly
      doubled (117.434.5 N vs. 66.4+/-31.4 N, respectively, p<0.05). These values were
      lower compared to the sham-operated side (89.7+/-15.3 N/mm and 332.0+/-50.8 N,
      respectively). The tangent modulus of the healing MCL (279.7+/-132.1 MPa vs.
      149.0+/-76.5 MPa, respectively) and stress at failure (15.7+/-4.1 MPa vs. 10.2+/
      3.9 MPa, respectively) both increased by more than 50% with SIS treatment
      (p<0.05). Yet, each remained lower compared to the sham-operated side (936.3+/
      283.6 MPa and 75.6+/-14.2 MPa, respectively). Blinded histological comparisons
      between the SIS-treated MCL and the non-treated control demonstrated
      qualitatively that the SIS treated group had increased cellularity, greater
      collagen density, and improved collagen fiber alignment. CONCLUSION: Healing of a
      gap MCL injury was significantly enhanced with SIS. The improved mechanical
      properties and histological appearance of the MCL suggest that SIS treatment
      improves the quality of tissue and renders the possibility for future studies
      investigating functional tissue engineering of healing ligaments.

PMID- 14656684
TI  - Effect of shock-wave therapy on patellar tendinopathy in a rabbit model.
AB  - This study investigated the effect of shock-wave therapy (SWT) on collagenase
      induced tendinopathy in the rabbit patellar tendon. Eighteen rabbits were treated
      by ultrasonography-guided injection of 0.025 ml collagenase into the patellar
      tendon in both knees. After tendinopathy was confirmed at 3 weeks post-treatment
      by the histological examination, SWT was initiated to the right patellar tendon
      involving 1500 cycles at 0.29 mJ/mm2 in two separated weekly courses from 4 weeks
      post-treatment. The rabbits were randomly divided into two groups, which were
      sacrificed at the 4th and 16th week after SWT, respectively. The histological
      examination, the mechanical and biochemical tests then were performed. The
      ultimate tensile load in the SWT tendon increased 7.03% at 4 week and 10.34% at
      16 week after treatment as compared to the sham group. Hydroxyproline
      concentrations increased in the SWT tendons over both the 4 and 16 weeks after
      treatment. Moreover, the pyridinoline concentration increased at the 4th week but
      decreased at 16th week as compared to the sham group. The histological
      examination demonstrated increased blast-like tenocyte at the 4th week, while
      more mature tenocyte with neovasculization at the 16th week. The result obtained
      here validates the effectiveness of the SWT in the established tendinopathy. SWT
      may increase collagen synthesis and collagen crosslink formation during early
      healing process.

PMID- 14656685
TI  - Ex vivo lipopolysaccharide (LPS)-induced TNF-alpha, IL-1beta, IL-6 and PGE2
      secretion in whole blood from Type 1 diabetes mellitus patients with or without
      aggressive periodontitis.
AB  - Several studies have demonstrated that diabetes is a risk factor for developing
      periodontal disease, increasing its prevalence and severity. Furthermore,
      periodontitis may impair the metabolic control and adequate treatment of diabetic
      patients. LPS from Gram-negative bacteria penetrates the periodontal tissues and
      subsequently recruits and activates immune cells. Progression to severe
      periodontitis with loss of supporting structures is mediated by several factors,
      including secretion of a broad spectrum of inflammatory and destructive (PGE2).
      mediators such as cytokines (TNF-alpha, IL-1b and IL-6), chemokines (IL-8) and
      prostaglandin E2. The aim of this work is to investigate differences in the TNF
      a, IL-1b and IL-6 expression and prostaglandin E2 (PGE2) release in blood from
      diabetic patients with and without aggressive periodontitis (AP) stimulated with
      lipopolysaccharide (LPS). For this purpose we recruited 29 Type 1 diabetes
      mellitus (DM) patients, 14 with AP and 15 without AP. Fourteen healthy
      individuals formed the control group. For cytokine expression and PGE2 secretion,
      an ex vivo whole blood culture system was used. Cytokines and PGE2 were detected
      by commercial immunometric assays. A wide range of inter-individual variability
      in spontaneous and LPS-induced TNF-alpha, IL-1b and IL-6 levels in patient groups
      and controls was found. The mean of spontaneous and LPS-induced TNF-alpha and IL
      1b levels did not differ significantly (p > 0.5) when patients were compared to
      control individuals. Although not significant, the spontaneous TNF-alpha, IL-1b
      and IL-6 levels in the group of Type 1 DM with AP were higher than in controls,
      while in diabetic patients without AP, these values were depressed in comparison
      with controls. In both groups of patients, the means of LPS-induced IL-6 levels
      were higher than the controls but the differences observed were not significant
      (p = 0.07). However, the LPS-induced PGE2 levels varied significantly when all
      groups were compared (p = 0.007). The means of LPS-induced PGE2 levels for Type 1
      diabetic patients with AP (p = 0.0009) and without AP (p = 0.024) were
      significantly higher than the levels observed for healthy controls. Finally, we
      conclude that Type 1 diabetic patients with or without AP did not express higher
      LPS-induced TNF-a, IL-1b and IL-6 levels than controls. However, the PGE2 levels
      released were significantly higher than those detected in controls.

PMID- 14656686
TI  - Natural killer (NK) cell-mediated cytolysis of Plasmodium falciparum-infected
      human red blood cells in vitro.
AB  - The ability of human NK cells to inhibit the growth in vitro of the asexual blood
      stages of Plasmodium falciparum was tested. Purified NK cells from donors with no
      prior exposure to malaria significantly inhibited parasite growth after 48 hours
      of co-culture in the presence of human immune serum. This inhibition was
      completely abrogated by pre-treatment of the NK cells with an anti-CD95 (anti
      Fas) monoclonal antibody and human Fas-Fc soluble protein. The level of growth
      inhibition was also substantially reduced by pre-treatment with an anti-CD56
      antibody. These two antibodies caused reductions, to varying levels, of the
      amounts of NK cell-derived granzyme B (GrB) and pro-inflammatory cytokines, but
      only the anti-CD95 antibody affected the production of soluble Fas ligand
      (sFasL). Direct destruction of parasite-infected red cells by NK cells, in the
      absence of serum, was also observed in a standard 51Cr cytotoxicity test, during
      which N-carboxybenzoxy-L-lysine thiobenzil ester (BLT esterase) activity, which
      catalyzes serine protease granule release, was detected. The results obtained are
      indicative of a novel mechanism of NK cell-mediated cytotoxic activity against
      Plasmodium falciparum-infected red cells, which is mediated in part by both Fas
      and by GrB.

PMID- 14656687
TI  - Local and peripheral cytokine response and CagA status of Helicobacter pylori
      positive patients with duodenal ulcer.
AB  - The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was
      investigated in H. pylori-positive patients with duodenal ulcer (DU). The
      concentrations of these cytokines in gastric antrum mucosal specimens from
      patients infected with H. pylori (n = 40) were determined by ELISA and compared
      with data on mucosal specimens from H. pylori-negative patients (n = 12).
      Nitrotyrosine was determined by ECL Western blotting. It was additionally
      investigated whether the tissue levels of the cytokines correlated with the
      peripheral cytokine levels, and the CagA status of the patients. The local TNF-a,
      IL-6 and IL-8 concentrations in the antral biopsy samples were significantly
      higher (p < 0.001) in the patients infected with H. pylori than in the samples
      from the H. pylori-negative subjects. There was a negative correlation between
      the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy
      specimens, considerable nitrotyrosine production was detected by ECL Western
      blotting. There was no significant difference in peripheral TNF-a and IL-6
      production between the DU patients and healthy blood donors (n = 100; 58% of whom
      were also H. pylori-positive). Only the in vitro IL-8-producing capacity was
      higher in the peripheral blood of the DU group after ex vivo induction with H.
      pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with
      DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This
      study suggests that besides the bacterial virulence factor, the host response,
      with an increased mucosal production of inflammatory cytokines and reactive
      oxygen and nitrogen species could be relevant to the gastric pathophysiology in
      H. pylori-induced DU. There is no generalized cytokine overproduction in these DU
      patients, but the moderate increase in in vitro IL-8 production might be of
      pathophysiological importance.

PMID- 14656688
TI  - Circulating VEGF and its soluble receptors sVEGFR-1 and sVEGFR-2 in patients with
      acute leukemia.
AB  - Angiogenesis plays an important role in the pathogenesis of acute leukemia, and
      vascular endothelial growth factor (VEGF) is a crucial, positive regulator of
      this process. The biological activity of VEGF is mediated by two different
      receptor tyrosine kinases: VEGFR-2 and VEGFR-1. The soluble form of VEGFR-1 is
      likely to be a negative regulator of VEGF availability, but the physiological
      role of sVEGFR-2 is still unclear. The plasma levels of sVEGFR-1 and sVEGFR-2 in
      patients with acute leukemia have not been investigated. We measured the plasma
      concentrations of VEGF and its two soluble receptors in 39 AML and 15 ALL
      patients as well as in the control group, using the ELISA assay. We also
      correlated the plasma levels of these proteins with disease status and known
      prognostic factors. The sVEGFR-1 level was significantly higher in patients with
      AML and ALL than in the healthy subjects (p < 0.002 and p < 0.03 respectively).
      The sVEGFR-2 level was significantly higher in AML patients compared with the
      control group (p < 0.03). The VEGF levels in AML and ALL patients and in healthy
      subjects did not differ significantly. The sVEGFR-1 level was higher in AML
      patients with > 50% of blasts in the bone marrow (BM), WBC > 20 G/L and elevated
      LDH level, than in the group with BM blasts < 50% (p < 0.01), WBC < 20 G/L (p <
      0.02) and a normal LDH level (p < 0.05). Positive correlations between sVEGFR-1
      level and WBC (p < 0.02),% of BM blasts (p < 0.05), the absolute blast count in
      peripheral blood (ABC) (p < 0.009) and LDH (p < 0.000001) were found. The sVEGFR
      1/VEGF ratio (R1) was calculated, and a positive correlation between R1 and ABC
      in AML (p < 0.03) was determined. A higher (above median) sVEGFR-1/VEGF ratio
      correlated with a lower CR rate and a shorter survival (p < 0.03 and p = 0.0007
      respectively). In conclusion, the plasma concentration of sVEGFR-1 is higher in
      leukemia patients than in healthy subjects and correlates with tumour burden and
      poor prognosis. The sVEGFR-1/VEGF ratio may be of greater prognostic value than
      VEGF alone. Further investigation is recommended to better determine their
      function.

PMID- 14656689
TI  - Serial immunoprecipitation assays for interferon--(IFN)-beta antibodies in
      multiple sclerosis patients.
AB  - We devised a sensitive, radioimmunoprecipitation assay (RIPA) for anti-interferon
      (IFN)-beta-binding antibody (BAB) detection. Our RIPA showed good agreement with
      a reference RIPA (mean difference, -3.2 +/- 10.6 AU), and detected BAB to both
      IFN-beta-1a and IFN-beta-1b. Neutralizing antibodies to IFN-b (NAB) were also
      determined with a standard method. BAB and NAB were measured in 393 serum samples
      from 77 multiple sclerosis (MS) patients treated with IFN-beta-1a or -1b, who
      were studied over two years, and subsequently classified as responders and non
      responders. BAB were found at higher concentrations, and more frequently
      detected, in IFN-beta-1b- than in IFN-beta-1a-treated patients, and, at highest
      titres, preferentially in patients who were positive for NAB. However, in our
      series of MS patients, both titres and frequency of detection of BAB or NAB did
      not differ between IFN-b responders and non-responders.

PMID- 14656690
TI  - Effect of IC14, an anti-CD14 antibody, on plasma and cell-associated chemokines
      during human endotoxemia.
AB  - To determine the role of CD14 in lipopolysaccharide (LPS)-induced release of
      chemokines, 16 humans were injected with LPS (4 ng/kg) preceded (-2 h) by
      intravenous IC14, an anti-human CD14 monoclonal antibody, or placebo. LPS
      elicited increases in interleukin (IL)-8 concentrations in plasma and in lysates
      of red blood cell (RBC), polymorphonuclear cell and mononuclear cell fractions,
      which were all reduced by IC14. LPS also induced rises in the plasma and RBC
      levels of monocyte chemoattractant protein (MCP)-1, which were diminished by
      IC14. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, chemokines that
      in contrast to IL-8 and MCP-1 can not bind to the Duffy antigen receptor for
      chemokines on RBCs, were only detected in plasma. IC14 attenuated the LPS-induced
      release of MIP-1beta, but not of MIP-1alpha. IL-8 and MCP-1, but not MIP-1alpha
      and MIP-1b, circulate in RBC-associated form during endotoxemia. LPS-induced
      chemokine release is, in part, mediated by an interaction with CD14.

PMID- 14656691
TI  - Serum interleukin-18 and nitric oxide activity in bladder carcinoma.
AB  - BACKGROUND: Both interleukin-18 and nitric oxide are multifunctional molecules
      that are involved in the different steps of carcinogenesis. METHODS: In the
      present study, we measured serum interleukin-18 and nitric oxide activity in 51
      bladder cancer patients with different tumor stage and grade, and in 8 healthy
      controls. Serum nitrite-nitrate levels were measured as an index of nitric oxide
      generation. RESULTS: Serum interleukin-18 levels were significantly higher in
      bladder cancer patients when compared to the control subjects (p > 0.05). Serum
      interleukin-18 levels were found to be higher in patients with Ta stage than
      patients with T1 and T2, T3, T4 stages and in patients with grade 1 tumors than
      patients with grade 2 and grade 3 tumors, but this was not statistically
      significant (p > 0.05). There was no significant difference in serum nitrite +
      nitrate levels between bladder cancer patients and control subjects. CONCLUSIONS:
      Elevated serum interleukin-18 levels in bladder carcinoma patients may be a
      result of host defence mechanism against the growth and progression of bladder
      cancer cells.

PMID- 14656692
TI  - Interleukin 1B gene polymorphism is associated with baseline C-reactive protein
      levels in healthy individuals.
AB  - C-reactive protein (CRP) is a sensitive marker of inflammation induced by both IL
      6 and IL-1. Thus, genetic variation in these genes could be associated with the
      variety in C-reactive protein levels, and therefore with the severity of the
      entire inflammatory response. Even a subtle elevation in baseline CRP levels in
      healthy individuals has been found to significantly increase the risk for
      cardiovascular diseases. Therefore, to find out the possible role of pro
      inflammatory cytokines in CRP baseline regulation we conducted a study of 338
      healthy blood donors whose CRP levels were determined and whose single nucleotide
      polymorphisms of IL1A(C/T)-889, IL1B(C/T)-511, IL1B(C/T) + 3954, IL6(G/C)-174 and
      ILRN (a VNTR) both genotyped and haplotyped. The data revealed an association
      between CRP levels and the IL1B + 3954 genotype. Also, the bilocus haplotype IL1B
      511*1/IL1B + 3954*2 was more frequent in subjects with below median CRP levels (<
      0.72 mg/l), and composite genotype analysis of IL1B-511/IL1B + 3954 supported
      this finding. Our findings suggest that in healthy people, basal CRP levels are
      regulated by IL1B but not by IL6 genetics.

PMID- 14656693
TI  - Cytokine patterns during dengue shock syndrome.
AB  - OBJECTIVE: To investigate the patterns of tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta), IL-6, interferon-gamma (IFN-gamma) and
      interleukin-1 receptor antagonist (IL-1Ra) during the course of dengue shock
      syndrome. DESIGN: Prospective clinical study. SETTING: Pediatric Intensive Care
      Unit, Dr. Kariadi Hospital, the university hospital of Diponegoro University,
      Semarang, Indonesia. PATIENTS: Fifty children with dengue shock syndrome.
      MEASUREMENTS: The plasma concentration and the ex vivo production, with and
      without lipopolysaccharide (LPS), of TNF-alpha, IL-1beta and IL-1Ra were measured
      in duplicate by nonequilibrium radioimmunoassay (RIA); IFN-gamma and IL-6 were
      measured by ELISA. RESULTS: During the acute phase, the plasma concentrations and
      the ex vivo production without LPS of IL-1Ra were considerably elevated and
      returned to normal on recovery. However, the ex vivo LPS-stimulated production of
      the proinflammatory cytokines TNF-alpha and IL-1beta were considerably depressed.
      Also, these concentrations returned towards normal on recovery. In non-survivors,
      the plasma concentrations of IL-6 and IL-1Ra were significantly higher than in
      survivors (p = 0.00001 and p = 0.0005, respectively). In addition, the ex vivo
      production of IL-1Ra in non-survivors was significantly higher than in survivors,
      both without LPS stimulation (p = 0.0008) and with LPS (p < 0.004). IL-1Ra was
      significantly associated with mortality (p = 0.007). CONCLUSION: Since IL-1Ra was
      significantly associated with mortality, this measurement may be used as an index
      of disease severity in dengue shock syndrome.

PMID- 14656694
TI  - Role of IL-10 in the distribution of B cell subsets in the mouse B-1 cell
      population.
AB  - The B lymphocyte compartment is comprised of B-1 and B-2 cells. The former is
      divided into B-1a, which express CD5, and B-1b cells which do not: both are self
      renewing, although the mechanisms are yet to be identified. IL-10-/- mice were
      used to delineate the role of the B cell activator IL-10 in this process. Its
      absence had no effect on the total number of B-1 cells, but decreased that of B
      1a cells (0.8 +/- 0.1 versus 1.7 +/- 0.2 x 10(6), p < 0.002), while increasing
      that of B-1b cells (1.9 +/- 0.4 versus 0.8 +/- 0.1 x 10(6), p < 0.03). The number
      of B-1a cells remained low in IL-10-injected IL-10-/- mice, whereas the excess of
      B-1b cells further increased (2.8 +/- 0.2 versus 1.6 +/- 0.4 x 10(6), p < 0.03).
      On the basis that Bax and Bad were augmented in B-1a cells, and Bcl-2 and Bcl-xL
      reduced, we conclude that the disappearance of B-1a cells, but not B-1b, in IL-10
      /- mice results from their enhanced susceptibility to apoptosis. In addition,
      culture of IL-10-/- B-1a and B-1b cells in the presence of IL-10 drives more of
      the latter than of the former into cycle (p < 0.02). Therefore, IL-10 exerts two,
      complementary effects on the distribution of B-1 cell sub-populations, rescuing B
      1a cells from apoptosis and encouraging B-1b cell proliferation.

PMID- 14656696
TI  - Increased serum CNTF level in patients with amyotrophic lateral sclerosis.
AB  - The role of ciliary neurotrophic factor (CNTF) in the etiopathogenesis of
      amyotrophic lateral sclerosis (ALS) is still not clear. The aim of this study was
      to measure serum CNTF level in patients with ALS. The study involved 36 ALS
      patients and 43 control group subjects. CNTF was measured by the enzyme-linked
      immunosorbent assay. Results showed that the serum CNTF level in whole group of
      ALS patients was significantly higher from those in the total control group
      subjects. CNTF level was not dependent on the clinical state of the ALS patients,
      type of ALS onset, or duration of the disease. Results indicate that CNTF may be
      a reactive component resulting from the disease, but it cannot be a marker of ALS
      activity. It is possible that the increase in serum CNTF level is the result of
      the muscle denervation seen in this disease.

PMID- 14656695
TI  - Th1-Th2 response in hyperprolactinemic mice infected with Salmonella enterica
      serovar Typhimurium.
AB  - Prolactin (PRL) is a pituitary hormone and a cytokine known to regulate several
      physiological functions. It plays a role in modulating the immune system of
      rodents and humans. A hormonal protection against listeria and salmonella
      infections has been previously ascribed to effects of PRL on immunocompetent
      cells. Here, the role of PRL in the Th1-Th2 response was evaluated based on the
      pattern of cytokines release by splenocytes from hyperprolactinemic mice infected
      with Salmonella enterica serovar Typhimurium. Hyperprolactinemia by pituitary
      graft reduced the number of bacteria in spleens of in vivo infected mice.
      Modulation of Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-10) cytokine production by
      splenic cells was found. Our results indicate that PRL can up-regulate IFN-c and
      IL-12 secretion in response to salmonella infection, confirming its in vivo
      immunostimulatory effect and suggesting hormonal participation in the genesis and
      sustenance of the Th1 response.

PMID- 14656698
TI  - Oxidant signaling in lung cells.

PMID- 14656699
TI  - Activation of K+ channels: an essential pathway in programmed cell death.
AB  - Cell apoptosis and proliferation are two counterparts in sharing the
      responsibility for maintaining normal tissue homeostasis. In recent years, the
      process of the programmed cell death has gained much interest because of its
      influence on malignant cell growth and other pathological states. Apoptosis is
      characterized by a distinct series of morphological and biochemical changes that
      result in cell shrinkage, DNA breakdown, and, ultimately, phagocytic death.
      Diverse external and internal stimuli trigger apoptosis, and enhanced K+ efflux
      has been shown to be an essential mediator of not only early apoptotic cell
      shrinkage, but also of downstream caspase activation and DNA fragmentation. The
      goal of this review is to discuss the role(s) played by K+ transport or flux
      across the plasma membrane in the regulation of the apoptotic volume decrease and
      apoptosis. Attention has also been paid to the role of inner mitochondrial
      membrane ion transport in the regulation of mitochondrial permeability and
      apoptosis. We provide specific examples of how deregulation of the apoptotic
      process contributes to pulmonary arterial medial hypertrophy, a major
      pathological feature in patients with pulmonary arterial hypertension. Finally,
      we discuss the targeting of K+ channels as a potential therapeutic tool in
      modulating apoptosis to maintain the balance between cell proliferation and cell
      death that is essential to the normal development and function of an organism.

PMID- 14656700
TI  - Expression and functional implications of CCR2 expression on murine alveolar
      epithelial cells.
AB  - Acute lung injury results in damage to the alveolar epithelium, leading to leak
      of proteins into the alveolar space and impaired gas exchange. Lung function can
      be restored only if the epithelial layer is restored. The process of
      reepithelialization requires migration of lung epithelial cells to cover denuded
      basement membranes. The factors that control the migration of lung epithelial
      cells are incompletely understood. We examined isolated murine type II alveolar
      epithelial cells (AECs) for expression of CC chemokine receptor 2 (CCR2) and
      functional consequences of the binding of the main CCR2 ligand monocyte
      chemoattractant protein-1 (MCP-1). We found that primary AECs bound MCP-1 and
      expressed CCR2 mRNA. These cells demonstrated functional consequences of CCR2
      expression with migration in response to MCP-1 in chemotaxis/haptotaxis assays.
      Primary AECs cultured from mice lacking CCR2 did not respond to MCP-1. Monolayers
      of AECs lacking CCR2 demonstrated delayed closure of mechanical wounds compared
      with AEC monolayers expressing CCR2. Delayed closure of mechanical wounds of wild
      type AECs was also demonstrated in the presence of anti-MCP-1 antibody. These
      data demonstrate for the first time that AECs express CCR2 and are capable of
      using this receptor for chemotaxis and healing of wounds. CCR2-MCP-1 interactions
      may be important in the process of reepithelialization after lung injury.

PMID- 14656701
TI  - Cytokine mRNA expression in unilateral ischemic-reperfused rat lung with salt
      solution supplemented with low-endotoxin or standard bovine serum albumin.
AB  - Our aim was to determine whether cytokine mRNA expression is induced by
      experimental manipulation including artificial perfusate or ischemia-reperfusion
      (I/R) in an isolated, perfused rat lung model. Constant pulmonary flow [Krebs
      Henseleit solution supplemented with low-endotoxin (LE) or standard (ST) bovine
      serum albumin 4%, 0.04 ml/g body wt] and ventilation were maintained throughout.
      Right and left pulmonary arteries were isolated, and the left pulmonary artery
      was occluded for 60 min and then reperfused for 30 min. Analysis of tumor
      necrosis factor-alpha, IL-1 beta, IL-6, IL-10, and IFN-gamma mRNA expression by
      RT-PCR and evaluation of vascular permeability by bronchoalveolar lavage (BAL)
      fluid albumin content were conducted separately in right and left lung. Both LE
      and ST groups (each 12 rats) showed increases in vascular permeability by I/R
      (BAL fluid albumin content: 5.53 +/- 1.55 vs. 15.63 +/- 8.87 and 4.76 +/- 2.71
      vs. 16.72 +/- 4.85 mg.ml BAL fluid-1.g lung dry wt-1, mean +/- SD; right vs. left
      lung in LE and ST groups, P < 0.05 between right and left). Cytokine mRNA
      expression was significantly higher in the I/R lung than in the control lung in
      the LE group, whereas it was higher in the control lung in the ST group (P <
      0.05). mRNAs of not only proinflammatory but also anti-inflammatory cytokines
      were expressed in I/R lung, which are expected to aggravate I/R injury. The
      reversed pattern of cytokine mRNA expression in the ST group was possibly due to
      the longer perfusion of control lung with perfusate containing endotoxin, which
      caused no lung damage without I/R.

PMID- 14656702
TI  - ET-1 induces cortical spreading depression via activation of the ETA
      receptor/phospholipase C pathway in vivo.
AB  - Recently, it has been shown that brain topical superfusion of endothelin (ET)-1
      at concentrations around 100 nM induces repetitive cortical spreading depressions
      (CSDs) in vivo. It has remained unclear whether this effect of ET-1 is related to
      a primary neuronal/astroglial effect, such as an increase in neuronal
      excitability or induction of interastroglial calcium waves, or a penumbra-like
      condition after vasoconstriction. In vitro, ET-1 regulates interastroglial
      communication via combined activation of ET(A) and ET(B) receptors, whereas it
      induces vasoconstriction via single activation of ET(A) receptors. We have
      determined the ET receptor profile and intracellular signaling pathway of ET-1
      induced CSDs in vivo. In contrast to the ET(B) receptor antagonist BQ-788 and
      concentration dependently, the ET(A) receptor antagonist BQ-123 completely
      blocked the occurrence of ET-1-induced CSDs. The ET(B) receptor antagonist did
      not increase the efficacy of the ET(A) receptor antagonist. Direct stimulation of
      ET(B) receptors with the selective ET(B) agonist BQ-3020 did not trigger CSDs.
      The phospholipase C (PLC) antagonist U-73122 inhibited CSD occurrence in contrast
      to the protein kinase C inhibitor Go-6983. Our findings indicate that ET-1
      induces CSDs through ET(A) receptor and PLC activation. We conclude that the
      induction of interastroglial calcium waves is unlikely the primary cause of ET-1
      induced CSDs. On the basis of the receptor profile, likely primary targets of ET
      1 mediating CSD are either neurons or vascular smooth muscle cells.

PMID- 14656703
TI  - Remodeling of excitation-contraction coupling in transgenic mice expressing ATP
      insensitive sarcolemmal KATP channels.
AB  - Reducing the ATP sensitivity of the sarcolemmal ATP-sensitive K(+) (K(ATP))
      channel is predicted to lead to active channels in normal metabolic conditions
      and hence cause shortened ventricular action potentials and reduced myocardial
      inotropy. We generated transgenic (TG) mice that express an ATP-insensitive
      K(ATP) channel mutant [Kir6.2(deltaN2-30,K185Q)] under transcriptional control of
      the alpha-myosin heavy chain promoter. Strikingly, myocyte contraction amplitude
      was increased in TG myocytes (15.68 +/- 1.15% vs. 10.96 +/- 1.49%), even though
      K(ATP) channels in TG myocytes are very insensitive to inhibitory ATP. Under
      normal metabolic conditions, steady-state outward K(+) currents measured under
      whole cell voltage clamp were elevated in TG myocytes, consistent with threshold
      K(ATP) activation, but neither the monophasic action potential measured in
      isolated hearts nor transmembrane action potential measured in right ventricular
      muscle preparations were shortened at physiological pacing cycles. Taken
      together, these results suggest that there is a compensatory remodeling of
      excitation-contraction coupling in TG myocytes. Whereas there were no obvious
      differences in other K(+) conductances, peak L-type Ca(2+) current (I(Ca))
      density (-16.42 +/- 2.37 pA/pF) in the TG was increased compared with the wild
      type (-8.43 +/- 1.01 pA/pF). Isoproterenol approximately doubled both I(Ca) and
      contraction amplitude in wild-type myocytes but failed to induce a significant
      increase in TG myocytes. Baseline and isoproterenol-stimulated cAMP
      concentrations were not different in wild-type and TG hearts, suggesting that the
      enhancement of I(Ca) in the latter does not result from elevated cAMP.
      Collectively, the data demonstrate that a compensatory increase in I(Ca)
      counteracts a mild activation of ATP-insensitive K(ATP) channels to maintain the
      action potential duration and elevate the inotropic state of TG hearts.

PMID- 14656704
TI  - NO and endogenous angiotensin II interact in the generation of renal sympathetic
      nerve activity in conscious rats.
AB  - Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats.
      However, whether NO tonically inhibits sympathetic outflow, or whether endogenous
      angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats
      is unknown. To address these questions, we determined the effects of NO synthase
      (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR)
      in conscious, unrestrained rats on normal (NS), high-(HS), and low-sodium (LS)
      diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When
      arterial pressure was kept at baseline with intravenous hydralazine, NOS
      inhibition with l-NAME (10 mg/kg i.v.) resulted in a profound decline in RSNA, to
      42 +/- 11% of control (P < 0.01), in NS animals. This effect was not sustained,
      and RSNA returned to control levels by 45 min postinfusion. l-NAME also caused
      bradycardia, from 432 +/- 23 to 372 +/- 11 beats/min postinfusion (P < 0.01), an
      effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS
      inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However,
      when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA
      after l-NAME infusion was absent in the LS rats, while the response in the HS
      group was unchanged by AIIRA. These findings indicate that, in contrast to our
      hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats,
      and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO
      is dependent on the action of endogenous ANG II.

PMID- 14656705
TI  - A model for human ventricular tissue.
AB  - The experimental and clinical possibilities for studying cardiac arrhythmias in
      human ventricular myocardium are very limited. Therefore, the use of alternative
      methods such as computer simulations is of great importance. In this article we
      introduce a mathematical model of the action potential of human ventricular cells
      that, while including a high level of electrophysiological detail, is
      computationally cost-effective enough to be applied in large-scale spatial
      simulations for the study of reentrant arrhythmias. The model is based on recent
      experimental data on most of the major ionic currents: the fast sodium, L-type
      calcium, transient outward, rapid and slow delayed rectifier, and inward
      rectifier currents. The model includes a basic calcium dynamics, allowing for the
      realistic modeling of calcium transients, calcium current inactivation, and the
      contraction staircase. We are able to reproduce human epicardial, endocardial,
      and M cell action potentials and show that differences can be explained by
      differences in the transient outward and slow delayed rectifier currents. Our
      model reproduces the experimentally observed data on action potential duration
      restitution, which is an important characteristic for reentrant arrhythmias. The
      conduction velocity restitution of our model is broader than in other models and
      agrees better with available data. Finally, we model the dynamics of spiral wave
      rotation in a two-dimensional sheet of human ventricular tissue and show that the
      spiral wave follows a complex meandering pattern and has a period of 265 ms. We
      conclude that the proposed model reproduces a variety of electrophysiological
      behaviors and provides a basis for studies of reentrant arrhythmias in human
      ventricular tissue.

PMID- 14656706
TI  - Genesis of the monophasic action potential: role of interstitial resistance and
      boundary gradients.
AB  - The extracellular potential at the site of a mechanical deformation has been
      shown to resemble the underlying transmembrane action potential, providing a
      minimally invasive way to access membrane dynamics. The biophysical factors
      underlying the genesis of this signal, however, are still poorly understood. With
      the use of data from a recent experimental study in a murine heart, a three
      dimensional anisotropic bidomain model of the mouse ventricular free wall was
      developed to study the currents and potentials resulting from the application of
      a point mechanical load on cardiac tissue. The applied pressure is assumed to
      open nonspecific pressure-sensitive channels depolarizing the membrane, leading
      to monophasic currents at the electrode edge that give rise to the monophasic
      action potential (MAP). The results show that the magnitude and the time course
      of the MAP are reproduced only for certain combinations of local or global
      intracellular and interstitial resistances that form a resting tissue length
      constant that, if applied over the entire domain, is smaller than that required
      to match the wave speed. The results suggest that the application of pressure not
      only causes local depolarization but also changes local tissue properties, both
      of which appear to play a critical role in the genesis of the MAP.

PMID- 14656707
TI  - Coronary artery diameter can be assessed reliably with transthoracic
      echocardiography.
AB  - We studied whether diameters of coronary arteries can be measured accurately with
      the use of transthoracic echocardiography (TTE). By knowing the anatomic diameter
      of the coronary artery together with coronary flow velocity it is possible to
      measure coronary flow volume more precisely by TTE. However, the suitability of
      TTE for measurement of diameters of all main epicardial coronary arteries has not
      been systematically validated. We measured the diameters of the left main (LM),
      left anterior descending (LAD), left circumflex (LCX), and right coronary
      arteries (RCA) with the use of TTE [manual two-dimensional (2D), color-Doppler,
      and automated 2D analysis] in 30 patients who had normal coronary anatomy. We
      compared these diameters to those measured with quantitative coronary angiography
      (QCA). We could measure diameters of LM, LAD, LCX, and RCA by TTE in up to 37%,
      63%, 7%, and 60% of patients, respectively. The overall correlation coefficients
      between TTE and QCA measurements were 0.83 (P < 0.01) with manual 2D analysis,
      0.82 (P < 0.01) with automated 2D analysis, and 0.94 (P < 0.01) with a color
      Doppler-based analysis. Interobserver variability of TTE measurements was low
      (coefficient of variation 5.4 +/- 4.6-7.5 +/- 8.8%). TTE is an accurate method to
      evaluate coronary artery diameter in patients with healthy coronary arteries.

PMID- 14656708
TI  - Exogenous nitric oxide generates ROS and induces cardioprotection: involvement of
      PKG, mitochondrial KATP channels, and ERK.
AB  - We examined whether cGMP-dependent protein kinase (PKG) and mitochondrial ATP
      sensitive potassium (K(ATP)) channels are involved in S-nitroso-N-acetyl
      penicillamine (SNAP)-induced reactive oxygen species (ROS) generation. SNAP
      significantly increased ROS generation in cardiomyocytes. This increase was
      suppressed by both 5-hydroxydecanoate (5-HD) and glibenclamide. Direct opening of
      mitochondrial K(ATP) channels with diazoxide led to ROS generation. The increased
      ROS generation was reversed by N-(2-mercaptopropionyl)glycine (MPG), a scavenger
      of ROS. Myxothiazol partially suppressed the ROS generation. KT-5823, an
      inhibitor of PKG, prevented ROS generation, indicating that PKG is required for
      ROS generation. In addition, 8-bromoguanosine 3',5'-cyclic monophosphate (8
      BrcGMP), an activator of PKG, induced ROS generation. The effect of 8-BrcGMP was
      reversed by either 5-HD or MPG. YC-1, an activator of guanylyl cyclase, also
      increased ROS production, which was reversed by 5-HD. Neither LY-294002 nor
      wortmannin, the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase),
      affected SNAP's action. In a whole heart study, SNAP significantly reduced
      infarct size. The anti-infarct effect of SNAP was abrogated by either MPG or 5
      HD. This effect was also blocked by PD-98059, an ERK inhibitor, but not by LY
      294002. A Western blotting study showed that SNAP significantly enhanced
      phosphorylation of ERK, which was reversed by MPG. These results suggest that
      SNAP-induced ROS generation is mediated by activation of PKG and mitochondrial
      K(ATP) channels and that opening of mitochondrial K(ATP) channels is the
      downstream event of PKG activation. ROS and mitochondrial K(ATP) channels
      participate in the anti-infarct effect of SNAP. Moreover, phosphorylation of ERK
      is the downstream signaling event of ROS and plays a role in the cardioprotection
      of SNAP.

PMID- 14656709
TI  - Low angiogenic potency induced by the implantation of ex vivo expanded CD117(+)
      stem cells.
AB  - Ex vivo expansion of stem cells might be a feasible method of resolving the
      problem of limited cell supply in cell-based therapy. The implantation of
      expanded CD34(+) endothelial progenitor cells has the capacity to induce
      angiogenesis. In this study, we tried to induce angiogenesis by implanting
      expanded CD117(+) stem cells derived from mouse bone marrow. After 2 wk of
      culture with the addition of several growth factors, the CD117(+) stem cells
      expanded approximately 20-fold and had an endothelial phenotype with high
      expression of CD34 and vascular endothelial-cadherin. However, >70% of these ex
      vivo expanded cells had a senescent phenotype by beta-galactosidase staining, and
      their survival and incorporation were poor after implantation into the ischemic
      limbs of mice. Compared with the PBS injection only, the microvessel density and
      the percentage of limb blood flow were significantly higher after the
      implantation of 2 x 10(5) freshly collected CD117(+) cells (P < 0.01) but not
      after the implantation of 2 x 10(5) expanded CD117(+) cells (P > 0.05). These
      data indicate that ex vivo expansion of CD117(+) stem cells has low potency for
      inducing therapeutic angiogenesis, which might be related to the cellular
      senescence during ex vivo expansion.

PMID- 14656710
TI  - Linoleic acid induces interleukin-8 production by Crohn's human intestinal smooth
      muscle cells via arachidonic acid metabolites.
AB  - Previously we reported that linoleic acid (LA), but not oleic acid, caused a
      marked increase in the secretion of IL-8 by Crohn's human intestinal smooth
      muscle (HISM) cells. Antioxidants inhibited this response, implicating a role for
      oxidative stress and NF-kappaB, a transcription factor for IL-8 that is activated
      by oxidative stress. In this study, we examined two mechanisms whereby LA, the
      dietary precursor for arachidonic acid (AA), could increase the production of IL
      8 via activation of AA pathways: 1) by generation of reactive oxygen species by
      the AA-pathway enzymes to activate NF-kappaB or 2) by AA metabolites. Normal and
      Crohn's HISM cells were exposed to LA, oxidizing solution (Ox), or oxidizing
      solution enriched with LA (OxLA). Exposure of cells to Ox or OxLA induced
      oxidative stress as determined by thiobarbituric acid reactive substances. In
      normal cells, Ox but not LA activated NF-kappaB as determined by transfection
      experiments and Western blot. In Crohn's cells, NF-kappaB was spontaneously
      activated and was not further activated by Ox or LA. In contrast, TNF-alpha
      markedly increased activation of NF-kappaB in both normal and Crohn's cells.
      These results indicated that LA did not increase IL-8 by activating NF-kappaB, so
      we evaluated the second mechanism of an effect of AA metabolites. In normal
      cells, OxLA, but not LA, markedly stimulated IL-8, whereas in Crohn's cells, both
      OxLA and LA stimulated IL-8. OxLA, also stimulated production of AA metabolites
      leukotriene B(4) (LTB(4)), PGE(2), and thromboxane B(2) (TXB(2)) by normal and
      Crohn's cells. To determine whether AA metabolites mediated the IL-8 response,
      cells were treated with OxLA plus indomethacin (Indo), a cyclooxygenase
      inhibitor, and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor. Both
      Indo and NDGA blocked the IL-8 response to OxLA. To determine more specifically a
      role for AA metabolites, AA was used. Similar to OxLA, OxAA stimulated production
      of IL-8 and AA metabolites. Pinane thromboxane, a selective thromboxane synthase
      inhibitor and receptor blocker, inhibited OxAA stimulation of TXB(2) and IL-8 in
      a dose-response manner. MK886, a selective 5-lipoxygenase inhibitor, inhibited
      OxAA stimulation of LTB(4) and IL-8 also in a dose-response manner. Analysis of
      specific gene products by RT-PCR demonstrated that HISM cells expressed receptors
      for both thromboxane and LTB(4). We conclude that AA metabolites mediated the IL
      8 response to LA in HISM cells. Both cyclooxygenase and lipoxygenase pathways
      were involved. LA did not increase IL-8 by activating NF-kappaB, but NF-kappaB
      appeared to be involved, because LA increased IL-8 only in situations where NF
      kappaB was activated, either spontaneously in Crohn's cells or by Ox in normal
      cells. We speculate that AA metabolites increased IL-8 production by enhancing NF
      kappaB-dependent transcription of IL-8.

PMID- 14656711
TI  - Rapid translocation of hepatic glucokinase in response to intraduodenal glucose
      infusion and changes in plasma glucose and insulin in conscious rats.
AB  - The rate of liver glucokinase (GK) translocation from the nucleus to the
      cytoplasm in response to intraduodenal glucose infusion and the effect of
      physiological rises of plasma glucose and/or insulin on GK translocation were
      examined in 6-h-fasted conscious rats. Intraduodenal glucose infusion (28 mg.kg(
      1).min(-1) after a priming dose at 500 mg/kg) elevated blood glucose levels
      (mg/dl) in the artery and portal vein from 90 +/- 3 and 87 +/- 3 to 154 +/- 4 and
      185 +/- 4, respectively, at 10 min. At 120 min, the levels had decreased to 133
      +/- 6 and 156 +/- 5, respectively. Plasma insulin levels (ng/ml) in the artery
      and the portal vein rose from 0.7 +/- 0.1 and 1.8 +/- 0.3 to 11.8 +/- 1.5 and
      20.2 +/- 2.0 at 10 min, respectively, and 12.4 +/- 3.1 and 18.0 +/- 4.8 at 30
      min, respectively. GK was rapidly exported from the nucleus as determined by
      measuring the ratio of the nuclear to the cytoplasmic immunofluorescence (N/C) of
      GK (2.9 +/- 0.3 at 0 min to 1.7 +/- 0.2 at 10 min, 1.5 +/- 0.1 at 20 min, 1.3 +/-
      0.1 at 30 min, and 1.3 +/- 0.1 at 120 min). When plasma glucose (arterial; mg/dl)
      and insulin (arterial; ng/ml) levels were clamped for 30 min at 93 +/- 7 and 0.7
      +/- 0.1, 81 +/- 5 and 8.9 +/- 1.3, 175 +/- 5 and 0.7 +/- 0.1, or 162 +/- 5 and
      9.2 +/- 1.5, the N/C of GK was 3.0 +/- 0.5, 1.8 +/- 0.1, 1.5 +/- 0.1, and 1.2 +/-
      0.1, respectively. The N/C of GK regulatory protein (GKRP) did not change in
      response to the intraduodenal glucose infusion or the rise in plasma glucose
      and/or insulin levels. The results suggest that GK but not GKRP translocates
      rapidly in a manner that corresponds with changes in the hepatic glucose balance
      in response to glucose ingestion in vivo. Additionally, the translocation of GK
      is induced by the postprandial rise in plasma glucose and insulin.

PMID- 14656712
TI  - NOS2 deficiency increases intestinal metabolism both in nonstimulated and
      endotoxemic mice.
AB  - Animal studies have suggested that nitric oxide (NO) synthases (NOS) play a role
      in the regulation of protein metabolism in endotoxemia. We therefore investigated
      the role of inducible NOS (NOS2) on intestinal protein and neuronal NOS (NOS1)
      and endothelial NOS (NOS3) on amino acid metabolism. Three groups of mice were
      studied: 1) wild-type (WT), 2) NOS2 knockout (NOS2-KO), and 3) NOS2-KO + N(omega)
      nitro-l-arginine methyl ester (NOS2-KO + l-NAME), both in nonstimulated and LPS
      treated conditions. By infusion of the stable isotopes l-[phenyl-(2)H(5)]Phe, l
      [phenyl-(2)H(2)]Tyr, l-[guanidino-(15)N(2)]Arg, and l-[ureido-(13)C;
      (2)H(2)]citrulline (Cit), intestinal protein, amino acid, and Arg/NO metabolism
      were studied on the whole body level and across intestine. In nonstimulated
      situations, NOS2 deficiency increased whole body protein turnover and intestinal
      Gln uptake and Cit production. In NOS2-KO + l-NAME, the above-mentioned changes
      were reversed. After LPS in WT, whole body NO and Cit production increased. In
      contrast to this, LPS decreased net intestinal Gln uptake, whole body NO, and Cit
      production in NOS2-KO mice. Treatment of NOS2-KO + l-NAME with LPS was lethal in
      eight of eleven mice (73%). The surviving mice in this group showed a major drop
      in intestinal protein breakdown and synthesis to almost zero. Thus both in
      baseline conditions and during endotoxemia, the absence of NOS2 upregulated NOS1
      and/or NOS3, which increased intestinal metabolism. The drop in intestinal
      protein metabolism in the endotoxemic NOS2-KO + l-NAME group might play a role in
      mortality in that group.

PMID- 14656713
TI  - ICC pacing mechanisms in intact mouse intestine differ from those in cultured or
      dissected intestine.
AB  - Pacing of mouse intestine is driven by spontaneous activity of a network of
      interstitial cells of Cajal in the myenteric plexus (ICC-MP). So far, highly
      dissected circular muscle (CM) strips from control and mutant mice lacking ICC-MP
      and isolated, cultured ICC from newborn control mice were used to analyze its
      properties. Using intact circular and longitudinal segments of intestine, we
      recently reported that there were both significant similarities and differences
      between pacing studied in segments and from isolated, dissected tissues. Here, we
      report additional similarities and differences in our model from those in highly
      reduced systems. Similar to cultured or dissected intestine, blockade of
      sarcoplasmic-endoplasmic reticulum Ca(2+) pumps with thapsigargin or
      cyclopiazonic acid reduced pacing frequency, but thapsigargin was less effective
      than in isolated, cultured ICC. Moreover, inhibition of inositol 1,4,5
      trisphosphate (IP(3)) receptors with xestospongin C, a putative inhibitor of
      IP(3) receptors, failed to affect pacing but successfully blocked increased
      pacing frequency by phorbol ester. 2-Aminoethoxy-diphenylborate, a putative
      blocker of IP(3)-mediated calcium release, caused a significant decrease in the
      amplitude and frequency of contractions. The mitochondrial uncoupler carbonyl
      cyanide p-trifluormethoxyphenylhydrazone blocked pacing and KCl-induced
      contractions at a concentration of 1 microM. The cyclic nucleotide agonists
      sodium nitroprusside (SNP), forskolin, and 8-bromo-cGMP inhibited pacing in CM.
      In longitudinal muscle (LM), SNP and forskolin had little effect on pacing.
      Furthermore, dibutyryl-cAMP did not affect pacing in CM or LM. These results
      suggest that pacing in intact intestine is under partly similar regulatory
      control as in more reduced systems. However, pacing in intact intestine is not
      affected by xestospongin C, which abolishes pacing in isolated, cultured ICC and
      exhibits attenuated responses to thapsigargin. Also, major differences between LM
      and CM suggest a separate pacemaker may drive LM.

PMID- 14656714
TI  - Tumor necrosis factor-alpha inhibits peroxisome proliferator-activated receptor
      gamma activity at a posttranslational level in hepatic stellate cells.
AB  - Diminished activity of peroxisome proliferator-activated receptor gamma
      (PPARgamma) is implicated in activation of hepatic stellate cells (HSC), a
      critical event in the development of liver fibrosis. In the present study, we
      investigated PPARgamma regulation by TNF-alpha in an HSC line designated as BSC.
      In BSC, TNF-alpha decreased both basal and ligand (GW1929)-induced PPARgamma mRNA
      levels without changing its protein expression. Nuclear extracts from BSC treated
      with TNF-alpha showed decreased binding of PPARgamma to PPAR-responsive element
      (PPRE) as determined by electrophoretic mobility shift assay. In BSC transiently
      transfected with a PPARgamma1 expression vector and a PPRE-luciferase reporter
      gene, TNF-alpha decreased both basal and GW1929-induced transactivation of the
      PPRE promoter. TNF-alpha increased activation of ERK1/2 and JNK, previously
      implicated in phosphorylation of Ser(82) of PPARgamma1 and resultant negative
      regulation of PPARgamma transactivity. In fact, TNF-alpha failed to inhibit
      transactivity of a Ser(82)Ala PPARgamma1 mutant in BSC. TNF-alpha-mediated
      inhibition of PPARgamma transactivity was not blocked with a
      Ser(32)Ala/Ser(36)Ala mutant of inhibitory NF-kappaBalpha (IkappaBalpha). These
      results suggest that TNF-alpha inhibits PPARgamma transactivity in cultured HSC,
      at least in part, by diminished PPARgamma-PPRE (DNA) binding and ERK1/2-mediated
      phosphorylation of Ser(82) of PPARgamma1, but not via the NF-kappaB pathway.

PMID- 14656715
TI  - Cortisol rapidly suppresses intracellular calcium and voltage-gated calcium
      channel activity in prolactin cells of the tilapia (Oreochromis mossambicus).
AB  - Cortisol was previously shown to rapidly (10-20 min) reduce the release of
      prolactin (PRL) from pituitary glands of tilapia (Oreochromis mossambicus). This
      inhibition of PRL release by cortisol is accompanied by rapid reductions in
      (45)Ca(2+) and cAMP accumulation. Cortisol's early actions occur through a
      protein synthesis-independent pathway and are mimicked by a membrane-impermeable
      analog. The signaling pathway that mediates rapid, nongenomic membrane effects of
      glucocorticoids is poorly understood. Using the advantageous characteristics of
      the teleost pituitary gland from which a nearly pure population of PRL cells can
      be isolated and incubated in defined medium, we examined whether cortisol rapidly
      reduces intracellular free calcium (Ca(i)(2+)) and suppresses L-type voltage
      gated ion channel activity in events that lead to reduced PRL release.
      Microspectrofluorometry, used in combination with the Ca(2+)-sensitive dye fura 2
      revealed that cortisol reversibly reduces basal and hyposmotically induced
      Ca(i)(2+) within seconds (P < 0.001) in dispersed pituitary cells. Somatostatin,
      a peptide known to inhibit PRL release through a membrane receptor-coupled
      mechanism, similarly reduces Ca(i)(2+). Under depolarizing [K(+)], the L-type
      calcium channel agonist BAY K 8644, a factor known to delay the closing of L-type
      Ca(2+) channels, stimulates PRL release in a concentration-dependent fashion (P <
      0.01). Cortisol (and somatostatin) blocks BAY K 8644-induced PRL release (P <
      0.01; 30 min), well within the time course over which its actions occur,
      independent of protein synthesis and at the level of the plasma membrane. Results
      indicate that cortisol inhibits tilapia PRL release through rapid reductions in
      Ca(i)(2+) that likely involve an attenuation of Ca(2+) entry through L-type
      voltage-gated Ca(2+) channels. These results provide further evidence that
      glucocorticoids rapidly modulate hormone secretion via a membrane-associated
      mechanism similar to that observed with the fast effects of peptides and
      neurotransmitters.

PMID- 14656716
TI  - Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and
      spontaneous physical activity in rats.
AB  - In humans, nonexercise activity thermogenesis (NEAT) increases with positive
      energy balance. The mediator of the interaction between positive energy balance
      and physical activity is unknown. In this study, we address the hypothesis that
      orexin A acts in the hypothalamic paraventricular nucleus (PVN) to increase
      nonfeeding-associated physical activity. PVN-cannulated rats were injected with
      either orexin A or vehicle during the light and dark cycle. Spontaneous physical
      activity (SPA) was measured using arrays of infrared activity sensors and night
      vision videotaped recording (VTR). O(2) consumption and CO(2) production were
      measured by indirect calorimetry. Feeding behavior was assessed by VTR.
      Regardless of the time point of injection, orexin A (1 nmol) was associated with
      dramatic increases in SPA for 2 h after injection (orexin A: 6.27 +/- 1.95 x
      10(3) beam break count, n = 24; vehicle: 1.85 +/- 1.13 x 10(3), n = 38). This
      increase in SPA was accompanied by compatible increase in O(2) consumption.
      Duration of feeding was increased only when orexin A was injected in the early
      light phase and accounted for only 3.5 +/- 2.5% of the increased physical
      activity. In a dose-response experiment, increases in SPA were correlated with
      dose of orexin A linearly up to 2 nmol. PVN injections of orexin receptor
      antagonist SB-334867 were associated with decreases in SPA and attenuated the
      effects of PVN-injected orexin A. Thus orexin A can act in PVN to increase
      nonfeeding-associated physical activity, suggesting that this neuropeptide might
      be a mediator of NEAT.

PMID- 14656717
TI  - Unlike insulin, amino acids stimulate p70S6K but not GSK-3 or glycogen synthase
      in human skeletal muscle.
AB  - Insulin stimulates muscle glucose disposal via both glycolysis and glycogen
      synthesis. Insulin activates glycogen synthase (GS) in skeletal muscle by
      phosphorylating PKB (or Akt), which in turn phosphorylates and inactivates
      glycogen synthase kinase 3 (GSK-3), with subsequent activation of GS. A rapamycin
      sensitive pathway, most likely acting via ribosomal 70-kDa protein S6 kinase
      (p70(S6K)), has also been implicated in the regulation of GSK-3 and GS by
      insulin. Amino acids potently stimulate p70(S6K), and recent studies on cultured
      muscle cells suggest that amino acids also inactivate GSK-3 and/or activate GS
      via activating p70(S6K). To assess the physiological relevance of these findings
      to normal human physiology, we compared the effects of amino acids and insulin on
      whole body glucose disposal, p70(S6K), and GSK-3 phosphorylation, and on the
      activity of GS in vivo in skeletal muscle of 24 healthy human volunteers. After
      an overnight fast, subjects received intravenously either a mixed amino acid
      solution (1.26 micromol.kg(-1).min(-1) x 6 h, n = 9), a physiological dose of
      insulin (1 mU.kg(-1).min(-1) euglycemic hyperinsulinemic clamp x 2 h, n = 6), or
      a pharmacological dose of insulin (20 mU.kg(-1).min(-1) euglycemic
      hyperinsulinemic clamp x 2 h, n = 9). Whole body glucose disposal rates were
      assessed by calculating the steady-state glucose infusion rates, and vastus
      lateralis muscle was biopsied before and at the end of the infusion. Both amino
      acid infusion and physiological hyperinsulinemia enhanced p70(S6K)
      phosphorylation without affecting GSK-3 phosphorylation, but only physiological
      hyperinsulinemia also increased whole body glucose disposal and GS activity. In
      contrast, a pharmacological dose of insulin significantly increased whole body
      glucose disposal, p70(S6K), GSK-3 phosphorylation, and GS activity. We conclude
      that amino acids at physiological concentrations mediate p70(S6K) but, unlike
      insulin, do not regulate GSK-3 and GS phosphorylation/activity in human skeletal
      muscle.

PMID- 14656718
TI  - Involvement of SSAO-mediated deamination in adipose glucose transport and weight
      gain in obese diabetic KKAy mice.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is located on outer surfaces of
      adipocytes and endothelial and vascular smooth muscle cells. This enzyme
      catalyzes deamination of methylamine and aminoacetone, leading to production of
      toxic formaldehyde and methylglyoxal, respectively, as well as hydrogen peroxide
      and ammonium. Several lines of evidence suggest that increased SSAO activity is
      related to chronic inflammation and vascular disorders related to diabetic
      complications. We found that a highly potent and selective SSAO inhibitor, (E)-2
      (4-fluorophenethyl)-3-fluoroallylamine (FPFA), was capable of reducing numbers of
      atherosclerotic lesions as well as weight gain in obese KKAy mice fed an
      atherogenic diet. SSAO inhibitors cause a moderate and long-lasting
      hyperglycemia. Such an increase in serum glucose is a result of reduction of
      glucose uptake by adipocytes. SSAO-mediated deamination of endogenous methylamine
      substrates induces adipocyte glucose uptake and lipogenesis. Highly selective
      SSAO inhibitors can effectively block induced glucose uptake. The results suggest
      that increased SSAO-mediated deamination may be concomitantly related to obesity
      and vascular disorders associated with type 2 diabetes.

PMID- 14656719
TI  - Compensatory responses of protein import and transcription factor expression in
      mitochondrial DNA defects.
AB  - Defects in mitochondrial DNA (mtDNA) evoke distinctive responses in the nuclear
      genome, leading to altered mitochondrial biogenesis. We used C(2)C(12) cells
      depleted of mtDNA (rho(-) cells) and fibroblasts from a mitochondrial
      encephalopathy, lactic acidosis, and strokelike episodes (MELAS) patient to
      examine adaptations of the protein import machinery and transcription factors
      involved in mitochondrial biogenesis. In rho(-) cells, Tom20 and Tim23 protein
      levels were reduced by 25% and 59%, whereas mtHSP70 was induced by twofold
      relative to control cells. These changes were accompanied by a 21% increase in
      enhanced yellow fluorescent protein (EYFP) import into mitochondria in rho(-)
      cells (P < 0.05). In contrast, in MELAS cells mtHSP70 was elevated by 70%,
      whereas Tom20 and Tom34 protein levels were increased by 45% and 112% relative to
      control values. EYFP import was not altered in MELAS cells. In rho(-) cells,
      protein levels of the transcription factors nuclear respiratory factor-1 (NRF-1)
      and transcription factor A (Tfam) declined by 33% and 54%, whereas no change was
      observed for the coactivator peroxisome proliferator receptor-gamma coactivator
      1alpha (PGC-1alpha). In contrast, Tfam was increased by 40% in MELAS cells. Rho(
      ) cells displayed reduced oxygen consumption (Vo(2)) and ATP levels, along with a
      twofold increase in lactate levels (P < 0.05). In electrically stimulated
      C(2)C(12) cells, 109%, 78%, 60%, and 67% increases were observed in mtDNA, Vo(2),
      cytochrome-c oxidase (COX) activity, and Tom34 levels, respectively (P < 0.05).
      Our findings suggest that compensatory adaptations occurred to maintain normal
      rates of protein import in response to mtDNA defects and support a role for
      contractile activity in reducing pathophysiology associated with mtDNA depletion.
      Because the expression of nuclear-encoded transcription factors and protein
      import machinery components was dependent on the type of mtDNA defect, these
      findings suggest involvement of distinct signaling cascades, each dependent on
      the type of mitochondrial defect, resulting in divergent changes in nuclear gene
      expression patterns.

PMID- 14656720
TI  - Structural characterization, tissue distribution, and functional expression of
      murine aminoacylase III.
AB  - Many xenobiotics are detoxified through the mercapturate metabolic pathway. The
      final product of the pathway, mercapturic acids (N-acetylcysteine S-conjugates),
      are secreted predominantly by renal proximal tubules. Mercapturic acids may
      undergo a transformation mediated by aminoacylases and cysteine S-conjugate beta
      lyases that leads to nephrotoxic reactive thiol formation. The deacetylation of
      cysteine S-conjugates of N-acyl aromatic amino acids is thought to be mediated by
      an aminoacylase whose molecular identity has not been determined. In the present
      study, we cloned aminoacylase III, which likely mediates this process in vivo,
      and characterized its function and structure. The enzyme consists of 318 amino
      acids and has a molecular mass (determined by SDS-PAGE) of approximately 35 kDa.
      Under nondenaturing conditions, the molecular mass of the enzyme is approximately
      140 kDa as determined by size-exclusion chromatography, which suggests that it is
      a tetramer. In agreement with this hypothesis, transmission electron microscopy
      and image analysis of aminoacylase III showed that the monomers of the enzyme are
      arranged with a fourfold rotational symmetry. Northern analysis demonstrated an
      approximately 1.4-kb transcript that was expressed predominantly in kidney and
      showed less expression in liver, heart, small intestine, brain, lung, testis, and
      stomach. In kidney, aminoacylase III was immunolocalized predominantly to the
      apical domain of S1 proximal tubules and the cytoplasm of S2 and S3 proximal
      tubules. The data suggest that in kidney proximal tubules, aminoacylase III plays
      an important role in deacetylating mercapturic acids. The predominant cytoplasmic
      localization of aminoacylase III may explain the greater sensitivity of the
      proximal straight tubule to the nephrotoxicity of mercapturic acids.

PMID- 14656721
TI  - Modulation of bone marrow-derived neutrophil signaling by H2O2: disparate effects
      on kinases, NF-kappaB, and cytokine expression.
AB  - Reactive oxygen species (ROS), including hydrogen peroxide (H2O2), are generated
      in increased amounts in pathological, biological processes and can play a role in
      signal transduction. Neutrophils often accumulate in acute inflammatory
      reactions, at sites where elevated concentrations of ROS are present. ROS have
      been demonstrated to participate in the activation of intracellular signaling
      pathways, including those involved in modulating nuclear accumulation and
      transcriptional activity of NF-kappaB. However, the role of ROS in affecting such
      events in neutrophils has not been examined. Using exposure of murine bone marrow
      neutrophils to H2O2 as a model of oxidative stress, we found both strong and
      persistent activation of ERK1/2, p38, JNK, and PKB, but not the p21-activated
      kinase. Stimulating the bone marrow-derived neutrophils with H2O2 did not affect
      nuclear translocation of NF-kappaB. However, production and secretion of the
      proinflammatory cytokine TNF-alpha in LPS-stimulated neutrophils were inhibited
      by H2O2. Exposure of LPS- or TNF-alpha-stimulated neutrophils to H2O2 decreased
      nuclear translocation of NF-kappaB. LPS-induced activation of the transcriptional
      factor AP-1 was also inhibited by H2O2. This inhibition of nuclear accumulation
      of NF-kappaB by H2O2 was not caused by an impaired capacity of LPS to stimulate
      the IKK pathway or to direct oxidative effects on NF-kappaB but rather reflected
      diminished degradation of IkappaB-alpha. These results indicate that oxidative
      stress, despite being able to selectively activate intracellular kinases in bone
      marrow-derived neutrophils, also inhibits NF-kappaB activation and associated TNF
      alpha expression. Such inhibitory effects on neutrophil activation may limit
      tissue damage produced by oxidative stress.

PMID- 14656722
TI  - Progressive dysregulation of transcription factors NF-kappa B and STAT1 in
      prostate cancer cells causes proangiogenic production of CXC chemokines.
AB  - The CXC chemokine family includes members that possess angiogenic and angiostatic
      properties. Angiogenic CXC chemokines are produced by prostate cancer cells and
      contribute to prostate tumor growth. Production of angiostatic CXC chemokines by
      prostatic cells has not been previously studied. Here we show that normal
      prostate epithelial (PZ-HPV-7) cells produce low amounts of angiogenic CXC
      chemokines, whereas prostate cancer cells from primary (CA-HPV-10) and metastatic
      (PC-3) tumors produce progressively greater amounts. These effects were caused by
      progressive increases in activation of the transcription factor nuclear factor
      kappa B in prostate cancer cells. Conversely, PZ-HPV-7 cells produced relatively
      high levels of angiostatic CXC chemokines, whereas CA-HPV-10 and PC-3 cells
      produced stepwise lower amounts. These effects were dependent on reduced
      activation of signal transduction and activator of transcription 1 (STAT1) in
      prostate cancer cells. These data suggest that there is progressive dysregulation
      of nuclear factor-kappa B and STAT1 in prostate cancer cells that leads to
      proangiogenic production of CXC chemokines.

PMID- 14656723
TI  - Accumulation of beta (m), a structural member of X,K-ATPase beta-subunit family,
      in nuclear envelopes of perinatal myocytes.
AB  - Recently discovered muscle-specific beta(m) protein is structurally closely
      related to the X,K-ATPase beta-subunits. However, it has a number of unique
      properties such as predominant localization in intracellular stores and lack of
      association with known X,K-ATPase alpha-subunits on heterologous coexpression. In
      this study, the primary structure of mouse beta(m) was determined and
      developmental regulation of the gene (ATP1B4) was analyzed. The expression is
      first detected at day 14 of gestation, is sharply increased at day 16, and
      reaches its maximum at day 18. After birth, the expression quickly decreases and
      is hardly detectable in adult mice. A more detailed subcellular localization
      study was undertaken, and its results indicate that beta(m) not only is located
      in sarcoplasmic reticulum but is concentrated in nuclear envelopes of both
      prenatal and postnatal skeletal muscles. Immunohistochemical studies show that
      beta(m) is specific to myocytes and, at the subcellular level, many nuclear
      envelopes are intensively labeled in both fetal and newborn skeletal muscles.
      Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear
      membranes from neonatal skeletal muscles. On transfection of human
      rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides
      intracellularly with significant enrichment in nuclear envelopes, whereas beta(m)
      with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm.
      Nuclear beta(m) apparently is not in association with Na,K-ATPase because we
      never detected its alpha-subunit in myonuclear membranes. These results indicate
      that beta(m) has a specialized function in mammalian perinatal myocytes,
      different from functions of other X,K-ATPase beta-subunits. The unique
      temporospatial distribution of beta(m) protein expression suggests its important
      role in development of growing skeletal muscle.

PMID- 14656725
TI  - Reciprocal interaction between seasonal testis and thyroid activity in Zembra
      Island wild rabbits (Oryctolagus cuniculus): effects of castration,
      thyroidectomy, temperature, and photoperiod.
AB  - The reproductive cycle of wild rabbits (Oryctolagus cuniculus) living in Zembra
      Island (North Tunisia) is dependent on an external factor, the photoperiod: the
      gonads are inhibited by long days and stimulated by short days or melatonin
      implants. Here we studied the role of an internal factor, thyroid hormones and
      the possible thyroid-gonadal interrelationships, in animals captured on Zembra
      Island and maintained in natural conditions of photoperiod and temperature. We
      determined the seasonal profile of the thyroid and testis cycles and investigated
      the effects of castration and thyroidectomy on the seasonal testosterone and
      thyroxine cycles. Plasma thyroxine and testosterone levels followed similar,
      parallel seasonal patterns, with a peak in autumn (October) and low values from
      January to August. In thyroidectomized animals, plasma testosterone levels,
      although significantly higher than those in controls (P < 0.001), remained low
      throughout the 13 mo of the experiment, and no testicular reactivation was
      observed in the fall. In castrated animals, despite the increase in thyroxine
      concentration in the 3 mo following castration (P < 0.01), plasma thyroxine
      levels remained low during the 2 yr of the study. We then investigated the
      combined effects of long days (16L:8D) and moderately high temperature (25
      degrees C) on these two endocrine axes. In constant gonado-inhibiting conditions
      (16L:8D), whether the temperature was kept constantly high or allowed to
      fluctuate naturally, no reactivation of the thyroid and testicular axes was
      observed in the fall. In control animals, the peaks of testosterone and thyroxine
      concentrations observed in September were larger (P < 0.001) than those in
      animals subjected to the same natural photoperiod conditions but with constantly
      high temperature. The lower level of autumnal testis stimulation (P < 0.001) in
      animals maintained in conditions of constant high temperature (25 degrees C) may
      be attributed to the low thyroxine levels induced by high temperature. These
      results clearly confirm that the thyroid and testicular cycles display similar
      seasonal variations and show that the thyroid and gonadal axes are strictly
      interdependent. This study provides the first demonstration, for a given species,
      that the seasonal reactivation of gonad activity is controlled by the thyroid,
      and thyroid activity is controlled by the gonads.

PMID- 14656726
TI  - In vivo effects of arsenite on meiosis, preimplantation development, and
      apoptosis in the mouse.
AB  - Inorganic arsenic, an environmental contaminant, produces a variety of stress
      responses in mammalian cells, including metabolic abnormalities accompanied by
      growth inhibition and carcinogenesis. Much of the toxicity of arsenic is known to
      stem from its uncoupling effects on mitochondria. Because previously we had shown
      that mitochondrial dysfunction can disrupt oocyte and embryo development, we
      investigated effects of arsenite on meiotic progression and early embryo
      development in mice. Six-week-old CD-1 mice were treated with 0 (solvent as
      control), 8 mg/kg (a dose previously established in mice as the maternal no
      observed-adverse-effect level), and 16 mg/kg doses of sodium arsenite every 2
      days for a total of seven i.p. injections ver a period of 14 days. The incidence
      of meiotic anomalies, characterized by spindle disruption and/or chromosomal
      misalignment, was significantly increased in arsenite-treated groups (25% after 8
      mg/kg and 62.5% after 16 mg/kg), compared to normal metaphase II in control
      oocytes. Further, arsenite treatment significantly decreased cleavage rates of
      zygotes at 24 h, morula formation at 72 h, and development to blastocysts at 96 h
      in a dose-dependent manner. The total cell number in developed blastocysts did
      not differ significantly between the 8 mg/kg arsenite treatment and control
      groups, but was significantly reduced in the 16 mg/kg arsenite treatment group.
      Moreover, the percentage of apoptotic nuclei was significantly increased in
      blastocysts following 16 mg/kg arsenite treatment. These data suggest that
      arsenite causes meiotic aberrations, which may contribute to decreased cleavage
      and preimplantation development, as well as increased apoptosis.

PMID- 14656727
TI  - Patterns of intracellular calcium oscillations in horse oocytes fertilized by
      intracytoplasmic sperm injection: possible explanations for the low success of
      this assisted reproduction technique in the horse.
AB  - In all species studied, fertilization induces intracellular Ca2+ ([Ca2+]i)
      oscillations required for oocyte activation and embryonic development. This
      species-specific pattern has not been studied in the equine, partly due to the
      difficulties linked to in vitro fertilization in this species. Therefore, the
      objective of this study was to use intracytoplasmic sperm injection (ICSI) to
      investigate fertilization-induced [Ca2+]i signaling and, possibly, ascertain
      problems linked to the success of this technology in the horse. In vivo- and in
      vitro-matured mare oocytes were injected with a single motile stallion sperm. Few
      oocytes displayed [Ca2+]i responses regardless of oocyte source and we
      hypothesized that this may result from insufficient release of the sperm-borne
      active molecule (sperm factor) into the oocyte. However, permeabilization of
      sperm membranes with Triton-X or by sonication did not alleviate the deficient
      [Ca2+]i responses in mare oocytes. Thus, we hypothesized that a step downstream
      of release, possibly required for sperm factor function, is not appropriately
      accomplished in horse oocytes. To test this, ICSI-fertilized horse oocytes were
      fused to unfertilized mouse oocytes, which are known to respond with [Ca2+]i
      oscillations to injection of stallion sperm, and [Ca2+]i monitoring was
      performed. Such pairs consistently displayed [Ca2+]i responses demonstrating that
      the sperm factor is appropriately released into the ooplasm of horse oocytes, but
      that these are unable to activate and/or provide the appropriate substrate that
      is required for the sperm factor delivered by ICSI to initiate oscillations.
      These findings may have implications to improve the success of ICSI in the equine
      and other livestock species.

PMID- 14656728
TI  - Follicle-restricted compartmentalization of transforming growth factor beta
      superfamily ligands in the feline ovary.
AB  - Ovarian follicular development, follicle selection, and the process of ovulation
      remain poorly understood in most species. Throughout reproductive life, follicle
      fate is balanced between growth and apoptosis. These opposing forces are
      controlled by numerous endocrine, paracrine, and autocrine factors, including the
      ligands represented by the transforming growth factor beta (TGFbeta) superfamily.
      TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth
      differentiation factor 9 (GDF-9) are present in the ovary of many animals;
      however, no comprehensive analysis of the localization of each ligand or its
      receptors and intracellular signaling molecules during folliculogenesis has been
      done. The domestic cat is an ideal model for studying ovarian follicle dynamics
      due to an abundance of all follicle populations, including primordial stage, and
      the amount of readily available tissue following routine animal spaying.
      Additionally, knowledge of the factors involved in feline follicular development
      could make an important impact on in vitro maturation/in vitro fertilization
      (IVM/IVF) success for endangered feline species. Thus, the presence and position
      of TGFbeta superfamily members within the feline ovary have been evaluated in all
      stages of follicular development by immunolocalization. The cat inhibin alpha
      subunit protein is present in all follicle stages but increases in intensity
      within the mural granulosa cells in large antral follicles. The inhibin betaA and
      betaB subunit proteins, in addition to the activin type I (ActRIB) and activin
      type II receptor (ActRIIB), are produced in primordial and primary follicle
      granulosa cells. Additionally, inhibin betaA subunit is detected in the theca
      cells from secondary through large antral follicle size classes. GDF-9 is
      restricted to the oocyte of preantral and antral follicles, whereas the type II
      BMP receptor (BMP-RII) protein is predominantly localized to primordial- and
      primary-stage follicles. TGFbeta1, 2, and 3 ligand immunoreactivity is observed
      in both small and large follicles, whereas the TGFbeta type II receptor (TGFbeta
      RII) is detected in the oocyte and granulosa cells of antral follicles. The
      intracellular signaling proteins Smad2 and Smad4 are present in the granulosa
      cell cytoplasm of all follicle size classes. Smad3 is detected in the granulosa
      cell nucleus, the oocyte, and the theca cell nucleus of all follicle size
      classes. These data suggest that the complete activin signal transduction pathway
      is present in small follicles and that large follicles primarily produce the
      inhibins. Our data also suggest that TGFbeta ligands and receptors are
      colocalized to large antral follicles. Taken together, the ligands, receptors,
      and signaling proteins for the TGFbeta superfamily are present at distinct points
      throughout feline folliculogenesis, suggesting discrete roles for each of these
      ligands during follicle maturation.

PMID- 14656729
TI  - Different testicular gene expression patterns in the first spermatogenic cycle of
      postnatal and vitamin A-deficient rat testis.
AB  - Spermatogenesis is a complicated process of germ cell differentiation, involving
      programmatic expression of diverse cell type- and developmental stage-specific
      genes. To date, the vitamin-A-deficiency (VAD) rats and postnatal rats are two
      models commonly used to study spermatogenesis. In the present study, we studied
      the expression of 1185 known genes in the vitamin-A-deficient and retinol
      reinitiated spermatogenesis of rat testis using Clontech Atlas rat cDNA
      expression arrays. The mRNA expression patterns of post-vitamin-A (PVA) testis on
      Days 15 and 35 were compared with those of the spermatogenic arrested rat testis
      on Day 0. About 9% (110/1185) of the genes studied were highly expressed. When
      compared with VAD rat testis on Day 0, 20 and 31 genes were differentially
      expressed by a factor of twofold or greater on Days 15 and 35, respectively. Four
      genes (cytochrome P450 17, sulfated glycoprotein 2, protein kinase inhibitor, and
      cathepsin L) that play important roles in spermatogenesis were selected and their
      gene expression patterns were confirmed by semiquantitative reverse transcription
      polymerase chain reaction. Comparison of the expression patterns of these genes
      between PVA-VAD and postnatal rat testis in developmentally matched stages
      revealed substantial differences during the early stages of spermatogenesis. This
      discrepancy could be caused by either the presence of arrested but mature somatic
      cells in the PVA-VAD testis that may contribute to a unique gene expression
      pattern in this model or the direct effect of retinol on spermatogenesis.
      Therefore, caution is needed in interpreting the gene expression data using the
      PVA-VAD and postnatal rat models in studying spermatogenesis in rat testes.

PMID- 14656730
TI  - Patterns and risk factors for systemic calcified atherosclerosis.
AB  - OBJECTIVE: Complex atherosclerotic lesions contain radio-opaque calcium
      hydroxyapatite deposits with the degree of calcification correlating with the
      extent of atherosclerosis. In this study, we aim to determine the patterns of
      systemic atherosclerotic calcification. METHODS AND RESULTS: Whole-body electron
      beam computed tomography scans were performed on 650 asymptomatic subjects to
      assess the carotid, coronary, proximal, and distal aorta and iliac vessels for
      atherosclerotic calcification. The mean age was 57.3 and 53% were male.
      Correlation patterns were similar in both genders, with the largest interbed
      correlations between the distal aorta and iliac vessels (r=0.51 to 0.60). The
      average man and woman had calcium earliest in the coronaries (younger than age 50
      years) and the distal aorta (age 50 to 60), respectively. The prevalence of
      calcium was greater than 80% for most beds in men older than age 70 and greater
      than 60% in all beds for women. Approximately on third of subjects younger than
      50 were free of calcified disease, whereas all subjects older than 70 were found
      to have some calcium. Age and hypertension were the dominant risk factors for
      systemic calcified atherosclerosis. CONCLUSIONS: This study confirms that there
      are significant correlations and risk factor associations for calcified
      atherosclerosis in different vascular beds.

PMID- 14656732
TI  - Alcohol consumption in relation to aortic stiffness and aortic wave reflections:
      a cross-sectional study in healthy postmenopausal women.
AB  - OBJECTIVE: Moderate alcohol consumption has been postulated to be
      cardioprotective. Such an effect might be reflected in large-artery properties,
      such as arterial stiffness and wave reflections. METHODS AND RESULTS: Three
      hundred seventy-one healthy postmenopausal women aged 50 to 74 years were sampled
      from a population-based study. Alcohol intake was calculated from a standardized
      questionnaire. Applanation tonometry was applied to assess the augmentation index
      and aortic pulse-wave velocity. Those drinking 1 to 3, 4 to 9, 10 to 14, and 15
      to 35 glasses of alcoholic beverages per week had a 0.044 (95% CI -0.47 to 0.56),
      -0.085 (95% CI -0.59 to 0.43), -0.869 (95% CI -1.44 to -0.29), and -0.225 (95% CI
      -0.98 to 0.53) m/s difference in mean pulse-wave velocity compared with
      nondrinkers, respectively, which indicates a J-shaped relationship. Adjustment
      for potential confounders of pulse-wave velocity or alcohol intake did not
      materially change the strength of the association. Adjustment for HDL further
      attenuated the relationship. The augmentation index was not related to alcohol
      consumption when adjustments were made for physiological determinants such as
      age, height, and ejection duration. CONCLUSIONS: Among postmenopausal women,
      alcohol consumption is inversely associated with pulse-wave velocity. This
      supports the presence of a decreased risk of cardiovascular disease with moderate
      alcohol consumption, which may be mediated in part by HDL cholesterol.

PMID- 14656731
TI  - Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in
      vascular disease.
AB  - Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a key
      signaling molecule in vascular homeostasis. Loss of NO bioavailability due to
      reduced synthesis and increased scavenging by reactive oxygen species is a
      cardinal feature of endothelial dysfunction in vascular disease states. The
      pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical
      determinant of eNOS activity: when BH4 availability is limiting, eNOS no longer
      produces NO but instead generates superoxide. In vascular disease states, there
      is oxidative degradation of BH4 by reactive oxygen species. However, augmentation
      of BH4 concentrations in vascular disease by pharmacological supplementation, by
      enhancement of its rate of de novo biosynthesis or by measures to reduce its
      oxidation, has been shown in experimental studies to enhance NO bioavailability.
      Thus, BH4 represents a potential therapeutic target in the regulation of eNOS
      function in vascular disease.

PMID- 14656733
TI  - Growth hormone induces low-density lipoprotein clearance but not bile acid
      synthesis in humans.
AB  - OBJECTIVE: Growth hormone (GH) induces hepatic low-density lipoprotein (LDL)
      receptors and lowers plasma cholesterol. We characterized the influence of GH
      treatment on plasma LDL clearance in normal humans and investigated the relative
      role of LDL receptor (LDLR) activity and stimulation of bile acid synthesis in
      subjects with different LDLR expression. METHODS AND RESULTS: Plasma clearance of
      autologous 125I-LDL was measured before and during 3 weeks of treatment with GH
      (0.1 IU/kg per day) in 9 healthy young males. Plasma LDL cholesterol was reduced
      by 13% and the fractional catabolic rate of LDL increased by 27%. More marked
      changes were seen in a patient with hypopituitarism substituted with GH (0.07
      IU/kg per day) for 3 months. In a second study, GH dose-dependently reduced LDL
      cholesterol and increased Lp(a) levels in 3 groups of males: younger and elderly
      healthy subjects and heterozygous familial hypercholesterolemia (FH). No effect
      on bile acid synthesis measured by the plasma marker 7alpha-hydroxy-4-cholesten-3
      one was observed. In an LDLR-deficient FH homozygote, LDL cholesterol was not
      affected by GH. CONCLUSIONS: GH treatment reduces plasma LDL cholesterol by
      inducing LDL clearance. In humans, LDLR expression is a prerequisite for this
      effect, whereas it is not related to stimulation of bile acid synthesis.

PMID- 14656734
TI  - Role of leukotriene B4 receptors in the development of atherosclerosis: potential
      mechanisms.
AB  - OBJECTIVE: Leukotriene B4 (LTB4), a potent leukocyte chemoattractant, is known to
      promote several inflammatory diseases, including atherosclerosis. We sought to
      determine mechanisms through which LTB4 modulates atherosclerosis in cell lines
      expressing LTB4 receptors, BLT-1, and in mice deficient in BLT-1 as well as
      macrophage cell lines derived from BLT-1+/+ and BLT-1-/- mice. METHODS AND
      RESULTS: Analysis of global changes in gene expression induced by LTB4 in rat
      basophilic leukemia cells (RBL-2H3) expressing the human BLT-1 showed highest
      fold increase in expression of fatty acid translocase/CD36 and the chemokine
      MCP1/JE/CCL2, which are critical in atherogenesis. To determine the importance of
      BLT-1 in atherogenesis, we crossed BLT-1-null mice with apolipoprotein (apo)-E
      deficient mice, which develop severe atherosclerosis. Deletion of BLT-1
      significantly reduced the lesion formation in apo-E-/- mice only during
      initiating stages (4 and 8 weeks) but had no effect on the lesion size in mice
      fed atherogenic diet for 19 weeks. Macrophage cell lines from BLT-1-deficient
      mice expressed the low-affinity LTB4 receptor, BLT-2, and exhibited chemotaxis to
      LTB4. CONCLUSIONS: The effects of LTB4 in atherosclerosis are likely mediated
      through the high-affinity BLT-1 and the low-affinity BLT-2 receptors. LTB4
      promotes atherosclerosis by chemo-attracting monocytes, by providing an
      amplification loop of monocyte chemotaxis via CCL2 production, and by converting
      monocytes to foam cells by enhanced expression of CD36 and fatty acid
      accumulation.

PMID- 14656736
TI  - Platelets of female mice are intrinsically more sensitive to agonists than are
      platelets of males.
AB  - OBJECTIVE: It has been reported that women fare worse after ischemic coronary
      events, but the mechanisms remain unclear. Because platelets play a central role
      in the formation of occlusive thrombi at sites of ruptured atherosclerotic
      plaques, we studied male/female paired mouse littermates for sex differences in
      platelet function. METHODS AND RESULTS: We compared platelet reactivity in
      male/female mouse littermates by monitoring agonist-induced fibrinogen (FGN)
      binding and platelet aggregation. Compared with the platelets from males,
      platelets from females bound more FGN in response to low concentrations of
      thrombin and collagen-related peptide. Female platelets also demonstrated greater
      aggregation in response to adenosine diphosphate and collagen-related peptide.
      Platelet protein tyrosine phosphorylation on activation also showed small
      differences between sexes. These differences are independent of platelet size and
      surface expression of alphaIIbbeta3 and GPIb-IX-V, and they were not blocked by
      apyrase or aspirin. The sex differences we observed were intrinsic to platelets,
      because they were observed in washed platelets, but not when platelets were in
      plasma. CONCLUSIONS: The platelets of female mice were more reactive than those
      of males in a manner independent of COX-1 and secreted ADP.

PMID- 14656735
TI  - Vascular endothelial growth factor activates PI3K/Akt/forkhead signaling in
      endothelial cells.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent angiogenic
      growth factor that promotes endothelial cell (EC) survival, migration, and
      permeability. The forkhead transcription factors FKHR, FKHRL1, and AFX are
      mammalian orthologues of DAF-16, a forkhead protein that controls longevity in
      Caenorhabditis elegans. In this study, we examined whether VEGF is coupled to
      phosphatidyl inositol 3-kinase (PI3K)/Akt/forkhead in ECs. METHODS AND RESULTS:
      We demonstrate that human ECs express members of the forkhead family (FKHR,
      FKHRL1, and AFX) and that VEGF modulates the phosphorylation, subcellular
      localization, and transcriptional activity of one or more of these isoforms by a
      PI3K/Akt signaling pathway. VEGF inhibited EC apoptosis, promoted DNA synthesis
      and the G(1)-to-S transition, and reduced expression of the cyclin-dependent
      kinase inhibitor p27(kip1). Each of these effects was blocked by the PI3K
      inhibitor LY294002 or by a phosphorylation-resistant mutant of FKHRL1, but not by
      wild-type FKHRL1. CONCLUSIONS: These results suggest that VEGF signaling in ECs
      is coupled to forkhead transcription factors through a PI3K/Akt-dependent
      pathway.

PMID- 14656737
TI  - Glargine and regular human insulin similarly acutely enhance endothelium
      dependent vasodilatation in normal subjects.
AB  - OBJECTIVE: Human insulin enhances the vasodilatory effect of acetylcholine (ACh),
      an endothelium-dependent vasodilator, in normal subjects. Structural changes in a
      long-acting insulin analog, insulin glargine, may change its binding properties
      to insulin receptor and structurally homologous receptors, such as the insulin
      like growth factor-1 receptor, and thereby alter its vascular effects. In the
      present study, we compared effects of glargine and regular human insulin on blood
      flow responses to endothelium-dependent and endothelium-independent vasoactive
      agents in vivo in normal subjects. METHODS AND RESULTS: Ten healthy men (age:
      33+/-9 years [mean+/-SD]; BMI: 23+/-2 kg/m2) were studied on two separate
      occasions in a double-blind, randomized, crossover fashion. In each study, blood
      flow responses to intrabrachial artery infusions of ACh and SNP were determined
      during infusion of saline and intravenously maintained normoglycemic
      hyperinsulinemia. Hyperinsulinemia (120 minutes; infusion rate: 1 mU/kg per
      minute) was created by infusing either insulin glargine or human regular insulin.
      Glargine and human regular insulin similarly stimulated whole-body glucose
      metabolism and suppressed serum free-fatty acid (FFA) concentrations. Endothelium
      independent blood flow responses to low (3 microg/min) and high (10 microg/min)
      doses of SNP were unaffected by insulin glargine (12.2+/-2.6 versus 13.4+/-4.6
      and 19.1+/-4.2 versus 19.6+/-5.1 mL/dL per minute, saline versus insulin, low-
      and high-dose) and regular human insulin (11.2+/-3.4 versus 12.0+/-5.2 and 16.8+/
      5.7 versus 18.4+/-7.7 mL/dL per minute, respectively). In contrast, endothelium
      dependent blood flow responses to low (7.5 microg/min) and high (15 microg/min)
      doses of ACh increased significantly and similarly by insulin glargine, 13.9+/
      4.8 versus 19.3+/-6.5 mL/dL per minute (saline versus insulin, +39%, P<0.01) for
      low-dose ACh and 17.3+/-6.3 versus 23.2+/-9.2 mL/dL per minute (+34%; P<0.02) for
      high-dose ACh, and regular human insulin, 11.5+/-6.0 versus 15.8+/-8.0 mL/dL per
      minute (+38%; P<0.05) and 14.0+/-7.5 versus 21.1+/-10.4 mL/dL per minute (+51%;
      P<0.01). CONCLUSIONS: Insulin glargine and regular human insulin have similar
      acute stimulatory effects on endothelium-dependent vasodilation in humans.

PMID- 14656738
TI  - Progression of carotid intima-media thickness and plasma antioxidants: the Los
      Angeles Atherosclerosis Study.
AB  - OBJECTIVE: Recent epidemiologic and animal model data suggest that oxygenated
      carotenoids are protective against early atherosclerosis. We assessed the
      association between atherosclerotic progression, measured by carotid intima-media
      thickness (IMT), and plasma levels of oxygenated and hydrocarbon carotenoids,
      tocopherols, retinol, and ascorbic acid. METHODS AND RESULTS: Participants were
      from an occupational cohort of 573 middle-aged women and men who were free of
      symptomatic cardiovascular disease at baseline. Ultrasound examination of the
      common carotid arteries, lipid level determination, and risk factor assessment
      were performed at baseline and 18-month follow-up. Plasma levels of antioxidants
      were determined at baseline only. Change in IMT was related to baseline plasma
      antioxidant levels in regression models controlling for covariates. In models
      adjusted for age, sex, and smoking status, 18-month change in IMT was
      significantly inversely related to the 3 measured oxygenated carotenoids (lutein,
      beta-cryptoxanthin, zeaxanthin; P<0.02 for all) and one hydrocarbon carotenoid,
      alpha-carotene (P=0.003). After adjusting for additional cardiac risk factors and
      potential confounders, including high-sensitivity C-reactive protein, these
      associations remained significant (P<0.05). CONCLUSIONS: These findings suggest
      that higher levels of plasma oxygenated carotenoids (lutein, zeaxanthin, beta
      cryptoxanthin) and alpha-carotene may be protective against early
      atherosclerosis.

PMID- 14656739
TI  - Modulation of factor V levels in plasma by polymorphisms in the C2 domain.
AB  - OBJECTIVE: Functional polymorphisms contributing to coagulation factor levels are
      preferential markers for association studies aimed at identifying prothrombic
      genetic components. METHODS AND RESULTS: Factor V (FV) microsatellite genotypes
      were found to be associated with FV levels (P=0.003). Single nucleotide
      polymorphisms analysis and sequencing of the promoter and of coding regions
      identified two polymorphisms (Met2120Thr, Asp2194Gly) present in 20% of the
      population (n=1013) that are responsible for genotype-phenotype associations. The
      effect of the Met2120Thr polymorphism, both in plasma (mean reduction of FV level
      in the heterozygous condition: 25%) and in recombinant FV studies (34%
      reduction), was comparable to that of the Asp2194Gly change (20% and 34%,
      respectively). The study of 10 subjects with a rare genotype indicated that the
      Asp2194Gly substitution is the functional determinant of the reduced FV levels
      associated with the FVHR2 haplotype. Among Leiden carriers, the doubly
      heterozygous condition for FV2120Thr was found to be associated with a
      significantly increased activated protein-C resistance (APCR) (P<0.05), and the
      doubly heterozygous condition for FV2194Gly was found to be more frequent
      (P=0.009) in symptomatic than in asymptomatic subjects. CONCLUSIONS: Extensive
      analysis of FV polymorphisms indicated that changes in the C2 domain modulate FV
      levels and might increase APCR and thrombotic risk in FV Leiden carriers through
      a pseudohomozygous mechanism.

PMID- 14656740
TI  - Weight reduction with very-low-caloric diet and endothelial function in
      overweight adults: role of plasma glucose.
AB  - OBJECTIVE: Obesity is associated with endothelial dysfunction that may contribute
      to the development of atherosclerosis. We studied whether weight reduction
      improves endothelial function in overweight individuals. METHODS AND RESULTS:
      Flow-mediated endothelium-dependent vasodilation of the brachial artery was
      measured in 67 adults (age: 46+/-7 years, body mass index: 35.2+/-5.4 kg/m2)
      before and after a 6-week weight reduction program induced by very-low-calorie
      diet (daily energy: 580 kcal/2.3 MJ). Caloric restriction reduced body weight
      from 101+/-18 to 90+/-17 kg. Flow-mediated vasodilation increased from 5.5%+/-3.7
      to 8.8%+/-3.7% (P<0.0001). Nitrate-mediated vasodilation was not significantly
      affected. The improvement in flow-mediated dilation was associated with the
      reduction in plasma glucose concentration (P=0.0003). This relationship was
      independent of changes in weight, serum lipids, oxidized LDL, C-reactive protein,
      adiponectin, blood pressure, and insulin. CONCLUSIONS: Weight reduction with very
      low-calorie diet improves flow-mediated vasodilation in obese individuals. This
      improvement is related to the reduction in plasma glucose concentration. These
      observations suggest that changes in glucose metabolism may determine endothelial
      vasodilatory function in obesity.

PMID- 14656741
TI  - Influence of gamma' fibrinogen splice variant on fibrin physical properties and
      fibrinolysis rate.
AB  - OBJECTIVE: A splice variant of fibrinogen, gamma', has an altered C-terminal
      sequence in its gamma chain. This gammaA/gamma' fibrin is more resistant to lysis
      than gammaA/gammaA fibrin. Whether the physical properties of gamma' and gammaA
      fibrin may account for the difference in their fibrinolysis rate remains to be
      established. METHODS AND RESULTS: Mechanical and morphological properties of
      cross-linked purified fibrin, including permeability (Ks, in cm2) and clot
      stiffness (G', in dyne/cm2), were measured after clotting gammaA and gamma'
      fibrinogens (1 mg/mL). gamma'/gamma' fibrin displayed a non-significant decrease
      in the density of fibrin fibers and slightly thicker fibers than gammaA/gammaA
      fibrin (12+/-2 fiber/10(-3) nm3 versus 16+/-2 fiber/10(-3) nm3 and 274+/-38 nm
      versus 257+/-41 nm for gamma'/gamma' and gammaA/gammaA fibrin, respectively;
      P=NS). This resulted in a 20% increase of the permeability constant (6.9+/-1.7
      10(-9) cm2 versus 5.5+/-1.9 10(-9) cm2, respectively; P=NS). Unexpectedly, gamma'
      fibrin was found to be 3-times stiffer than gammaA fibrin (72.6+/-2.6 dyne/cm2
      versus 25.1+/-2.3 dyne/cm2; P<0.001). Finally, there was a 10-fold decrease of
      the fibrin fiber lysis rate. CONCLUSIONS: Fibrinolysis resistance that arises
      from the presence of gammaA/gamma' fibrinogen in the clot is related primarily to
      an increase of fibrin cross-linking with only slight modifications of the clot
      architecture.

PMID- 14656742
TI  - Endothelial nitric oxide synthase: a new paradigm for gene regulation in the
      injured blood vessel.
AB  - Advances in our understanding of the molecular mechanisms involved in the
      constitutive and regulated expression of endothelial nitric oxide synthase (eNOS)
      mRNA expression present a new level of complexity to the study of endothelial
      gene regulation in health and disease. Recent studies highlight the contribution
      of both transcription and RNA stability to net steady-state mRNA levels of eNOS
      in vascular endothelium, introducing a new paradigm to gene regulation in the
      injured blood vessel. Constitutive eNOS expression is dependent on basal
      transcription machinery in the core promoter, involving positive and negative
      protein-protein and protein-DNA interactions. Chromatin-based mechanisms and
      epigenetic events also regulate expression of eNOS at the transcriptional level
      in a cell-restricted fashion. Although constitutively active, important
      physiological and pathophysiologic stimuli alter eNOS gene transcription rates.
      For instance, eNOS transcription rates increase in response to
      lysophosphatidylcholine, shear stress, and TGF-beta, among others. Under basal
      conditions, eNOS mRNA is extremely stable. Surprisingly, posttranscriptional
      mechanisms have emerged as important regulatory pathways in the observed
      decreases in eNOS expression in some settings. In models of inflammation,
      proliferation/injury, oxidized low-density lipoprotein treatment, and hypoxia,
      eNOS mRNA destabilization plays a significant role in the rapid downregulation of
      eNOS mRNA levels.

PMID- 14656743
TI  - Interferon regulatory factor-1 mediates PPARgamma-induced apoptosis in vascular
      smooth muscle cells.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) possesses
      general beneficial effects on the cardiovascular system, such as inhibition of
      vascular lesion formation and atherosclerosis. However, molecular mechanisms for
      these effects are yet to be fully defined. The aim of this study is to elucidate
      whether interferon regulatory factor-1 (IRF-1), a transcriptional factor with
      anti-proliferative and pro-apoptotic properties, mediates PPARgamma-induced
      apoptosis in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Using
      Northern and Western blot analyses, we documented that PPARgamma ligands,
      including ciglitazone, troglitazone, and GW7845, significantly increased IRF-1
      expression in VSMCs; however, the PPARalpha ligand (Wy14643) and PPARdelta ligand
      (GW0742) did not affect its expression. PPARgamma-induced IRF-1 expression was
      abrogated by pretreatment with the PPARgamma antagonist GW9662. In contrast,
      adenoviral expression of PPARgamma in VSMCs dramatically increased IRF-1 level.
      Furthermore, PPARgamma activation increased IRF-1 promoter activity but did not
      affect IRF-1 mRNA stability. Finally, reducing IRF-1 expression by antisense
      technology attenuated PPARgamma-induced VSMC apoptosis through decreasing cyclin
      dependent kinase inhibitor p21(cip1) and caspase-3 activity. CONCLUSIONS: Our
      data demonstrate that IRF-1 is a novel PPARgamma target gene and mediates
      PPARgamma-induced VSMC apoptosis.

PMID- 14656744
TI  - Progressive lung disease and surfactant dysfunction with a deletion in surfactant
      protein C gene.
AB  - Mutations in the surfactant protein (SP)-C gene are responsible for familial and
      sporadic interstitial lung disease (ILD). The consequences of such mutations on
      pulmonary surfactant composition and function are poorly understood. To determine
      the effects of a mutation in the SP-C gene on surfactant, we obtained lung tissue
      at the time of transplantation from a 14-mo-old infant with progressive ILD. An
      in-frame 9-bp deletion spanning codons 91-93 in Exon 3 of the SP-C gene was
      present on one allele; neither parent carried this deletion. SP-C mRNA was
      present in normal size and amount. By immunofluorescence, proSP-C was aggregated
      within alveolar Type II cells in a compartment separate from SP-B. In airway
      surfactant, there was little or no mature SP-B or SP-C; SP-A content was
      increased. Minimum surface tension was increased (20 mN/m, normal < 5 mN/m). Type
      II cells contained normal and disorganized appearing lamellar bodies by electron
      microscopy. This spontaneous deletion on one allele of the SP-C gene was
      associated with sporadic ILD and abnormalities in surfactant composition and
      function. We propose that a dominant negative effect on surfactant protein
      metabolism and function results from aggregation of misfolded proSP-C and
      subsequent cell injury and inflammation.

PMID- 14656745
TI  - Toll-like receptors in normal and cystic fibrosis airway epithelial cells.
AB  - Toll-like receptors (TLRs) mediate cellular responses to diverse microbial
      ligands. The distribution and function of TLRs in airway cells were studied to
      identify which are available to signal the presence of inhaled pathogens and to
      establish if differences in TLR expression are associated with the increased
      proinflammatory responses seen in cystic fibrosis (CF). Isogenic, polarized CF
      and control bronchial epithelial cell lines, human airway cells in primary
      culture, and cftr null and wild-type mice were compared. TLRs 1-10, MD2, and
      MyD88 were expressed in CF and normal cells. Only TLR2 transcription was modestly
      increased in CF as compared with normal epithelial cells following bacterial
      stimulation. TLR2 was predominantly at the apical surface of airway cells and was
      mobilized to cell surface in response to bacteria. TLR4 was present in a more
      basolateral distribution in airway cells, but appeared to have a limited role in
      epithelial responses. Lipopolysaccharide failed to activate nuclear factor-kappaB
      in these cells, and TLR2 dominant negative but not TLR4 dominant negative mutants
      inhibited activation by both Gram-negative and Gram-positive bacteria. Increased
      availability of TLR2 at the apical surfaces of CF epithelial cells is consistent
      with the increased proinflammatory responses seen in CF airways and suggests a
      selective participation of TLRs in the airway mucosa.

PMID- 14656746
TI  - Matrix metalloproteinase-9-deficient dendritic cells have impaired migration
      through tracheal epithelial tight junctions.
AB  - When sampling inhaled antigens, dendritic cells (DC) must penetrate the tight
      junction (TJ) barrier while maintaining the TJ seal. In matrix metalloproteinase
      (MMP)-9-deficient mice, in vivo experiments suggest that migration of DC into air
      spaces is impaired. To examine the underlying mechanisms, we established a well
      defined in vitro model using mouse tracheal epithelial cells and mouse bone
      marrow DC (BMDC). Transmigration was elicited with either macrophage inflammatory
      protein (MIP)-1alpha or MIP-3beta in a time-dependent manner. Control MMP-9(+/+)
      BMDC cultured with granulocyte macrophage-colony-stimulating factor for 7 d
      showed a 30-fold greater transepithelial migration toward MIP-3beta than MIP
      1alpha, indicating a more mature DC phenotype. MMP-9(-/-) BMDC as well as MMP
      9(+/+) BMDC in the presence of the MMP inhibitor GM6001, although showing a
      similar preference for MIP-3beta, were markedly impaired in their ability to
      traverse the epithelium. Expression levels of CCR5 and CCR7, however, were
      similar in both MMP-9(-/-) and MMP-9(+/+) BMDC. Expression of the integral TJ
      proteins, occludin and claudin-1, were examined in BMDC before and after
      transepithelial migration. Interestingly, occludin but not claudin-1 was degraded
      following transepithelial migration in both MMP-9(-/-) and control BMDC. In
      addition, there was a > 2-fold increase in claudin-1 expression in MMP-9(-/-) as
      compared with control BMDC. These observations indicate that occludin and claudin
      1 are differentially regulated and suggest that the lack of MMP-9 may affect
      claudin-1 turnover.

PMID- 14656747
TI  - Primary ciliary dyskinesia: diagnostic and phenotypic features.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disease characterized by
      abnormalities in ciliary structure/function. We hypothesized that the major
      clinical and biologic phenotypic markers of the disease could be evaluated by
      studying a cohort of subjects suspected of having PCD. Of 110 subjects evaluated,
      PCD was diagnosed in 78 subjects using a combination of compatible clinical
      features coupled with tests of ciliary ultrastructure and function. Chronic
      rhinitis/sinusitis (n = 78; 100%), recurrent otitis media (n = 74; 95%), neonatal
      respiratory symptoms (n = 57; 73%), and situs inversus (n = 43; 55%) are strong
      phenotypic markers of the disease. Mucoid Pseudomonas aeruginosa (n = 12; 15%)
      and nontuberculous mycobacteria (n = 8; 10%) were present in older (> 30 years)
      patients with PCD. All subjects had defects in ciliary structure, 66% in the
      outer dynein arm. Nasal nitric oxide production was very low in PCD (nl/minute;
      19 +/- 17 vs. 376 +/- 124 in normal control subjects). Rigorous clinical and
      ciliary phenotyping and measures of nasal nitric oxide are useful for the
      diagnosis of PCD. An increased awareness of the clinical presentation and
      diagnostic criteria for PCD will help lead to better diagnosis and care for this
      orphan disease.

PMID- 14656748
TI  - Human leukocyte antigen class I alleles and the disease course in sarcoidosis
      patients.
AB  - Several lines of evidence suggest a genetic predisposition to sarcoidosis, and
      strong associations have been shown with the major histocompatibility complex
      gene complex. In this study on Scandinavian sarcoidosis patients, we investigated
      any influence on the outcome of disease by human leukocyte antigen (HLA) class I
      alleles alone and in combination with selected class II alleles. HLA-B*07
      independently increased the risk for persistent sarcoidosis (odds ratio [OR],
      1.9; 95% confidence interval [CI], 1.0-3.7), as well as for resolving disease
      (OR, 2.7; CI, 1.1-6.2), suggesting an influence on factors common to both forms
      of sarcoidosis. The common allele combination A*03, B*07, DRB1*15 was most
      strongly associated with persistent disease (OR, 4.7; CI, 2.2-10.2) and was found
      in 25.3% of patients with persistent disease versus 7.1% of healthy control
      subjects. HLA-B*08 tended to increase separately the risk for resolving disease
      (OR, 2.4; CI, 0.7-8.0), as well as for persistent disease (OR, 2.2; CI, 0.8-6.1).
      Other HLA class I associations were mainly secondary to their linkages to DRB1*03
      and DRB1*15, respectively. The influence of HLA class I alleles on sarcoidosis
      thus seems more pronounced than previously thought, and both HLA class I and
      class II should be relevant to evaluate in the clinical management of sarcoidosis
      patients.

PMID- 14656749
TI  - The impact of intravenous fat emulsion administration in acute lung injury.
AB  - The aim of this study was to evaluate the effect of parenteral nutrition
      containing medium- and long-chain triglycerides on the function of the
      respiratory system and to investigate mechanisms involved in this process. We
      studied 13 patients with acute respiratory distress syndrome (ARDS), 8 receiving
      lipid and 5 placebo, and 6 without ARDS, receiving lipid. Bronchoalveolar lavage
      (BAL) was performed before and 1 hour after administration of lipid or placebo.
      In patients with ARDS, lipid administration resulted in deterioration of
      oxygenation (Pa(O(2))/FI(O(2)): from 129 +/- 37 to 95 +/- 42), compliance of
      respiratory system (from 39.2 +/- 12 to 33.1 +/- 9.2 ml/cm H(2)O), and pulmonary
      vascular resistance (from 258 +/- 47 to 321 +/- 58 dyne x s x cm(-5)). In the BAL
      fluid of the same group, an increase in total protein and phospholipid
      concentrations, phospholipase activities, platelet-activating factor and
      neutrophils, as well as alterations in BAL lipid profile were observed. No
      significant changes were observed in the control or in the ARDS-Placebo groups.
      In conclusion, this study indicates that administration of medium- and long-chain
      triglycerides in patients with ARDS causes alterations in lung function and
      hemodynamics. Inflammatory cells, possibly activated by lipids, release
      phospholipase A(2) and platelet-activating factor, enhancing edema formation,
      inflammation, and surfactant alterations.

PMID- 14656750
TI  - Junior versus senior physicians for informing families of intensive care unit
      patients.
AB  - To compare the effectiveness of information delivered to family members of
      critically ill patients by junior and senior physicians, we performed a
      prospective randomized multicenter trial in 11 French intensive care units.
      Patients (n = 220) were allocated at random to having their family members
      receive information by only junior or only senior physicians throughout the
      intensive care unit stay; there were 92 and 93 evaluable cases in the junior and
      senior groups, respectively, with no significant differences in baseline
      characteristics. Between Days 3 and 5, one family representative per patient was
      evaluated for comprehension of the diagnosis, prognosis, and treatment in the
      patient; satisfaction with information and care; and presence of symptoms of
      anxiety and depression. No significant differences were found between the two
      groups for any of these three criteria. Family members informed by a junior
      physician were more likely to feel they had not been given enough information
      time (additional time wanted: 3 [0-6.5] vs. 0 [0-5] minutes, p = 0.01) and to
      have sought additional explanations from their usual doctor (48.9 vs. 34.4%, p =
      0.004). Specialty residents, if given opportunities for acquiring experience, can
      become proficient in communicating with families and share this task with senior
      physicians.

PMID- 14656751
TI  - Regulation of mite allergen-pulsed murine dendritic cells by respiratory
      syncytial virus.
AB  - Dendritic cells (DCs) are the only antigen-presenting cells that determine T-cell
      differentiation and play an important role in both allergy and viral infection.
      Respiratory syncytial virus (RSV) can infect DCs and affect their functions. The
      aim of this study was to determine the interaction between RSV infection and
      Dermatophagoides farinae allergen (D. farinae) sensitization on the development
      of allergy at the DC level. Murine bone marrow-derived DCs were prepared and
      treated as: control; D. farinae-pulsed DCs (D. farinae-DCs); ultraviolet
      inactivated RSV challenged; RSV-infected, D. farinae-pulsed plus ultraviolet
      inactivated RSV-challenged; and D. farinae-pulsed plus RSV-infected. In in vitro
      experiments, we compared the expression of costimulatory molecules and cytokine
      production between the six groups of DCs. Another group of naive mice were then
      intranasally inoculated with these DCs, after which intranasal challenge with D.
      farinae was performed to develop allergic airway inflammation in vivo. In
      comparison with D. farinae-DCs, D. farinae-pulsed plus RSV-infected DCs showed
      helper T cell (Th) 1-favored expression of costimulatory molecules and cytokine
      production. Allergic airway inflammation induced by intranasal instillation of D.
      farinae-DCs was abrogated when infected with RSV, which was associated with a
      concomitant suppression of Th2 response in the lung. Our results indicated that
      RSV suppresses D. farinae-DCs to induce Th2 response both in vitro and in vivo
      through regulation of expression of surface markers and production of
      immunoregulatory cytokines.

PMID- 14656752
TI  - A mathematical model of tissue-blood carbon dioxide exchange during hypoxia.
AB  - A two-compartment mass transport model of tissue CO(2) exchange is developed to
      examine the relative contributions of blood flow and cellular hypoxia (dysoxia)
      to increases in tissue and venous blood CO(2) concentration. The model assumes
      perfectly mixed homogeneous conditions, steady-state equilibrium, and CO(2)
      production occurring exclusively at the tissues. The behavior of the model is
      compared with published data derived from an isolated dog hindlimb preparation
      subjected to either reductions in blood flow (ischemic hypoxia) or decreases in
      arterial PO(2) (hypoxic hypoxia). The results of the model corroborate the
      experimental finding of greater venous and tissue CO(2) concentrations with
      ischemic hypoxia than with hypoxic hypoxia. The model also predicts increases in
      tissue CO(2) concentration under conditions of adequate O(2) supply if CO(2)
      transfer from tissue to blood becomes impaired. Consequently, from a theoretical
      perspective, it appears that increases in the tissue or venous blood CO(2)
      concentration are neither sensitive nor specific markers of tissue dysoxia. The
      results of the model support the notion that changes in tissue and venous blood
      CO(2) concentration during dysoxia reflect primarily alterations in vascular
      perfusion and not scarcity in cellular energy supply.

PMID- 14656753
TI  - Kinetics of bone marrow eosinophilopoiesis and associated cytokines after
      allergen inhalation.
AB  - Allergen inhalation is associated with increased eosinophil/basophil progenitors
      in bone marrow 24 hours after allergen inhalation. This study examined the
      kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early,
      responders (n = 12). Dual responders, in contrast to isolated early responders,
      develop significant sputum and blood eosinophilia and prolonged airway
      hyperresponsiveness. Bone marrow aspirates were taken before and 5, 12, 24, and
      48 hours after allergen inhalation. In dual responders, increases in interleukin
      (IL)-3-responsive progenitors were detected as early as 5 hours after allergen
      inhalation, and IL-5-responsive progenitors were detected at 12 and 24 hours. No
      changes were detected in isolated early responders. Bone marrow IL-5 protein
      levels increased at 12 and 24 hours in dual responders only and these increases
      correlated with increases in IL-5-responsive progenitors. In addition, bone
      marrow IFN-gamma levels increased in dual responders at 48 hours. These data
      demonstrate that, in dual responders, there is allergen-induced activation of an
      eosinophilopoietic process that is rapid and sustained, and a relationship
      between increased bone marrow IL-5 levels and increased eosinophil production. We
      propose that after allergen inhalation, time-dependent changes in cytokine levels
      in the bone marrow control differentiation of eosinophil/basophil progenitors.

PMID- 14656754
TI  - Cough-generated aerosols of Mycobacterium tuberculosis: a new method to study
      infectiousness.
AB  - The concentration and size distribution of infectious aerosols produced by
      patients with pulmonary tuberculosis (TB) has never been directly measured. We
      aimed to assess the feasibility of a method that we developed to collect and
      quantify culturable cough-generated aerosols of Mycobacterium tuberculosis.
      Subjects were recruited from a referral hospital and most had multidrug-resistant
      TB. They coughed into a chamber containing microbial air samplers while cough
      frequency was measured during two 5-minute sessions. Cough-generated aerosol
      cultures were positive in 4 of 16 subjects (25%) with smear-positive pulmonary
      TB. There was a rapid decrease in the cough-generated aerosol cultures within the
      first 3 weeks of effective treatment. Culture-positive cough aerosols were
      associated with lack of treatment during the previous week (p = 0.007), and there
      was a trend in the association with cough frequency (p = 0.08). The size
      distributions of these aerosols were variable, but most particle sizes were in
      the respirable range. Quantification of viable cough-generated aerosols is
      feasible and offers a new approach to study infectiousness and transmission of M.
      tuberculosis and other airborne pathogens.

PMID- 14656755
TI  - Influenza vaccination in children with asthma: randomized double-blind placebo
      controlled trial.
AB  - There is little evidence that influenza vaccination reduces asthma exacerbations.
      We determined whether influenza vaccination is more effective than placebo in 6
      18-year-old children with asthma. We performed a randomized, double-blind,
      placebo-controlled trial. Parenteral vaccination with inactivated influenza
      vaccine or placebo took place approximately November 1, and children were
      followed until April 1 of the next year. Airway symptoms were reported in a
      diary. When symptom scores reached a predefined level, a pharyngeal swab was
      taken. Primary outcome was the number of asthma exacerbations associated with
      virologically proven influenza infection. Three hundred forty-nine children were
      assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for
      influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18
      in the placebo group, a difference of 33% favoring placebo (31% after adjustment
      for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma
      exacerbations were of similar severity in both groups; they lasted 3.1 days
      shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p =
      0.06). We conclude that influenza vaccination did not result in a significant
      reduction of the number, severity, or duration of asthma exacerbations caused by
      influenza. Additional studies are warranted to justify routine influenza
      vaccination of children with asthma.

PMID- 14656756
TI  - Developmental approaches to kidney tissue engineering.
AB  - Recent advances in our understanding of the developmental biology of the kidney,
      as well as the establishment of novel in vitro model systems, have potential
      implications for kidney tissue engineering. These advances include delineation of
      the roles of a number of growth factors in the developmental programs of
      branching morphogenesis and mesenchymal differentiation, a new understanding of
      the roles of the extracellular matrix, identification of potential "renal" stem
      cells, the ex vivo propagation and subsequent recombination of isolated
      components of the kidney, and successful transplantation of renal primordia into
      adult hosts. This review will examine these advances in the context of approaches
      to tissue engineering. Finally, novel approaches that synthesize advances in both
      cell-based and organ-based approaches are proposed.

PMID- 14656757
TI  - Kidney function in early diabetes: the tubular hypothesis of glomerular
      filtration.
AB  - At the onset of diabetes mellitus, the glomerular filtration rate becomes
      supranormal. Discovery science has identified many abnormalities in the early
      diabetic kidney that apparently contribute to this phenotype. A serviceable
      understanding of the early diabetic kidney requires this information to fit
      together. It is the purpose of this article to present an archetype that explains
      multiple nuances of kidney function in early diabetes. We refer to this archetype
      as the "tubular hypothesis of glomerular filtration." Its basic tenet is that
      strange effects of diabetes on glomerular filtration stem from primary effects on
      the proximal tubule or loop of Henle that impact glomerular filtration by
      feedback through the macula densa. This theory can explain diabetic
      hyperfiltration, a paradoxical effect of dietary salt on glomerular filtration
      rate in diabetes, and the renal response to dietary protein and amino acid
      infusion in diabetes. The discussion centers on the kidney as an integrated
      system of parts rather than on the specific cellular mechanisms that comprise
      those parts.

PMID- 14656758
TI  - Inward current oscillation underlying tonic contraction caused via ETA receptors
      in pig detrusor smooth muscle.
AB  - Endothelin-1 (ET-1) is a powerful vasoconstricting peptide. Recent studies showed
      synthesis of ET-1 and the presence of ET receptors in urinary bladder smooth
      muscle cells. In the present study, we investigated the possible role of ET-1 in
      detrusor contraction and its underlying mechanisms in terms of electrical
      activity. ET-1 caused dose-dependent tonic contraction of bladder smooth muscle
      strips. Whole cell patch-clamp experiments revealed that ET-1 induced a single
      transient inward current in the majority of detrusor cells and that additional
      inward current oscillations were induced in one-third of the cells. The inward
      current oscillation and tonic contraction shared several characteristic features:
      1) both activities lasted for a considerable time after ET-1 washout and 2) only
      prior application of ETA receptor antagonists, not ETB receptor antagonists,
      significantly suppressed ET-1-induced contractions and the oscillating inward
      currents. It was concluded that the inward current oscillation underlies ET-1
      induced tonic contraction. Experiments with ion substitution and channel blockers
      suggested that periodic activation of Ca2+-activated Cl- channels caused the
      oscillating inward currents.

PMID- 14656759
TI  - Ureagenesis: evidence for a lack of hepatic regulation of acid-base equilibrium
      in humans.
AB  - Ureagenesis in the liver consumes up to 1,000 mmol of HCO3-/day in humans as a
      result of 2NH4+ + 2HCO3- --> urea + CO2 + 3H2O. Whether the liver contributes to
      the regulation of acid-base equilibrium by controlling the rate of ureagenesis
      and, therefore, HCO3- consumption in response to changes in plasma acidity has
      not been adequately evaluated in humans. Rates of ureagenesis were measured in
      eight healthy volunteers during control, chronic metabolic acidosis (induced by
      oral administration of CaCl2 3.2 mmol.kg body wt-1.day-1 for 11 days), and
      recovery as well as during bicarbonate infusion (200 mmol over 240 min; acute
      metabolic alkalosis). Rates of ureagenesis were correlated negatively with plasma
      HCO3- concentration both during adaption to metabolic acidosis and during the
      chronic, steady-state phase. Thus ureagenesis, an acidifying process, increased
      rather than decreased in metabolic acidosis. During bicarbonate infusion, rates
      of ureagenesis decreased significantly. Thus ureagenesis did not appear to be
      involved in the regulated elimination of excess HCO3-. The finding of a negative
      correlation between ureagenesis and plasma HCO3- concentration over a wide range
      of HCO3- concentrations, altered both chronically and acutely, suggests that the
      ureagenic process per se is maladaptive for acid-base regulation and that
      ureagenesis has no discernible homeostatic effect on acid-base equilibrium.

PMID- 14656760
TI  - Smad expression during kidney development.
AB  - Signaling by the transforming growth factor (TGF)-beta superfamily is important
      during kidney development. Here, we describe the spatial and temporal expression
      patterns of the Smads, the transcription factors that translate TGF- signals into
      gene expression. RT-PCR data and in situ hybridization analysis showed that the
      receptor-regulated (R) Smads (Smad1, -2, -3, -5, and -8), the common partner Smad
      (Smad4), and the inhibitory (I) Smads (Smad6 and -7) were all expressed during
      mouse kidney development from embryonic day 12 until the end of nephrogenesis at
      postnatal day 15. Each Smad had a distinct spatial distribution. All were
      expressed by mesenchymal cells in the nephrogenic zone and were downregulated
      once these cells began to epithelialize. The common partner Smad, Smad4, was
      present in uninduced mesenchymal cells and at ureteric bud tips. The bone
      morphogenetic-responsive R-Smads, Smad1, -5, and -8, were mainly expressed in the
      nephrogenic zone, whereas the TGF-- responsive R-Smads were predominantly noted
      in the medullary interstitium. Expression of the I-Smad Smad7 was also seen in
      mesenchymal cells in the interstitium. Based on the observed patterns of
      expression, we speculate that individual or combinations of Smads may play
      specific roles in cell-fate determination during kidney development.

PMID- 14656761
TI  - A vibrator prevents streaming during close-arterial infusion into the kidney.
AB  - Close-arterial infusion of test substances allows one to study the responses of a
      selected vascular bed without inducing confounding systemic effects.
      Unfortunately, laminar flow patterns within the artery cause streaming of the
      injected factor, so that distribution within the target organ is not homogeneous.
      We describe a reliable method of overcoming these problems. Specifically, we
      attach a vibrator (i-Vibe egg) to the syringe containing the test substance. We
      showed that, without vibration, infusion of a solution of Evans blue (0.5%
      wt/vol) results in uneven distribution of the dye in the kidney. Vibration of the
      syringe during infusion allows for uniform coloration of the kidney surface.
      There is also functional improvement of drug distribution during vibration. Renal
      blood flow was measured during intrarenal infusion of phenylephrine (150 microl,
      0.05-0.5 microg). Vibration caused a significant leftward shift in the dose
      response curve, i.e., the phenylephrine-induced reduction in renal blood flow was
      enhanced by vibration. This cheap, simple method for ensuring adequate mixing of
      intra-arterially infused substances will facilitate not only the study of renal
      function in the rat but also infusion of test and therapeutic substances into
      other organs.

PMID- 14656762
TI  - 1alpha-Hydroxylase gene ablation and Pi supplementation inhibit renal
      calcification in mice homozygous for the disrupted Npt2a gene.
AB  - Disruption of the major renal Na-phosphate (Pi) cotransporter gene Npt2a in mice
      leads to a substantial decrease in renal brush-border membrane Na-Pi cotransport,
      hypophosphatemia, and appropriate adaptive increases in renal 25-hydroxyvitamin
      D3-1alpha-hydroxylase (1alphaOHase) activity and the serum concentration of 1,25
      dihydroxyvitamin D3 [1,25(OH)2D]. The latter is associated with increased
      intestinal Ca absorption, hypercalcemia, hypercalciuria, and renal calcification
      in Npt2-/- mice. To determine the contribution of elevated serum 1,25(OH)2D
      levels to the development of hypercalciuria and nephrocalcinosis in Npt2-/- mice,
      we examined the effects of 1alphaOHase gene ablation and long-term Pi
      supplementation on urinary Ca excretion and renal calcification by microcomputed
      tomography. We show that the urinary Ca/creatinine ratio is significantly
      decreased in Npt2-/-/1alphaOHase-/- mice compared with Npt2-/- mice. In addition,
      renal calcification, determined by estimating the calcified volume to total renal
      volume (CV/TV), is reduced by 80% in Npt2-/-/1alphaOHase-/- mice compared with
      that in Npt2-/- mice. In Npt2-/- mice derived from dams fed a 1% Pi diet and
      maintained on the same diet, we observed a significant decrease in urinary
      Ca/creatinine that was also associated with 80% reduction in CV/TV when compared
      with counterparts fed a 0.6% diet. Taken together, the present data demonstrate
      that both 1alphaOHase gene ablation and Pi supplementation inhibit renal
      calcification in Npt2-/- mice and that 1,25(OH)2D is essential for the
      development of hypercalciuria and nephrocalcinosis in the mutant strain.

PMID- 14656763
TI  - Na channels in the rat connecting tubule.
AB  - Epithelial Na channels were investigated using patch-clamp techniques in
      connecting tubule (CNT) segments isolated from rat kidney. Cell-attached patches
      with Li+ in the patch pipette contained channels with conductances for inward
      currents of 13-16 pS and slow opening and closing kinetics, similar to properties
      of Na channels in the cortical collecting tubule (CCT). Macroscopic amiloride
      sensitive currents (INa) were also observed under whole cell clamp conditions.
      These currents were undetectable in cells from control rats but were large when
      the animals were infused with aldosterone (1,380+/-340 pA/cell at a holding
      potential of -100 mV) or fed a high-K diet (670+/-260 pA/cell) for 1 wk. Under
      both of these conditions, currents in cells of the CNT were two- to fourfold
      larger than currents in cells of the CCT of the same animals. In aldosterone
      treated animals, currents in cells of the initial collecting tubule (iCT) were
      intermediate, such that the relative magnitude of INa was as follows: CNT > iCT >
      CCT. Quantitative analysis of the results suggests that the maximal capacity of
      the aggregate population of CNTs to reabsorb Na could be as high as 18
      micromol/min, or approximately 10% of the filtered load of Na. This capacity is
      approximately 10 times higher than that of the CCT.

PMID- 14656764
TI  - Adaptation of the myoglobin knockout mouse to hypoxic stress.
AB  - Myoglobin knockout (myo-/-) mice were previously reported to show no obvious
      phenotype but revealed several compensatory mechanisms that include increases in
      cardiac capillary density, coronary flow, and hemoglobin. The aim of this study
      was to investigate whether severe hypoxic stress can exhaust these compensatory
      mechanisms and whether this can be monitored on the gene and protein level. Myo-/
      and wild-type (WT) mice we e exposed to hypoxia (10% O(2)) fo 2 wk. Thereafter
      hemodynamic parameters were investigated by invasive measurement combined with
      magnetic resonance imaging. Cardiac gene and protein expression were analyzed
      using cDNA arrays and two-dimensional gel electrophoresis plus mass spectrometry,
      respectively. Hematocrit levels increased from 44% (WT) and 48% (myo-/-) to 72%
      in both groups. Similar to WT controls, hypoxic myo-/- animals maintained stable
      cardiovascular function (mean arterial blood pressure 82.4 mmHg, ejection
      fraction 72.5%). Cardiac gene expression of hypoxic myo-/- mice differed
      significantly from WT controls in 17 genes (e.g., keratinocyte lipid binding
      protein +202%, cytochrome c oxidase Vb +41%). Interestingly, hypoxia inducible
      factor-1alpha remained unchanged in both groups. Proteome analysis revealed
      reduced levels of heart fatty acid-binding protein and heat shock protein 27 both
      in hypoxic myo-/- and WT mice. Our data thus demonstrate that myo-/- mice do not
      decompensate du ing hypoxic st ess but a e surprisingly well adapted. Changes in
      ene gy metabolism of fatty acids may contribute to the robustness of myoglobin
      deficient mice.

PMID- 14656766
TI  - Feeding and temperature responses to intravenous leptin infusion are differential
      predictors of obesity in rats.
AB  - Obesity is frequently associated with leptin resistance. The present study
      investigated whether leptin resistance in rats is present before obesity
      develops, and thus could underlie obesity induced by 16 wk exposure to a liquid,
      palatable, high-energy diet (HED). Before HED exposure, male Wistar rats
      (weighing between 330 and 360 g) received intravenous infusions of 20 microg
      leptin 2 h before dark (approximately 57 microg/kg rat). Relative to saline
      infusion, this caused a highly variable effect on food intake (ranging between 
      94 and +129%), with food intake suppression that appeared negatively correlated
      with HED-induced increases in body weight gain, caloric intake, adiposity, and
      plasma leptin levels. In contrast, leptin's thermogenic response was positively
      correlated to body weight gain linked to weights of viscera, but not to
      adiposity. Before HED exposure, leptin unexpectedly increased food intake in some
      rats (fi+, n = 8), whereas others displayed the normal reduction in food intake
      (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels,
      retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and
      chow-fed rats. These parameters were also higher in HED-exposed fi-rats relative
      to chow rats, except for plasma leptin concentrations. It is concluded that
      leptin's reduced efficacy to suppress food intake could predict obesity on an
      HED. An unexpected orexigenic effect of leptin might potentially contribute to
      this as well.

PMID- 14656765
TI  - Phenotypic modulation of cultured bladder smooth muscle cells and the expression
      of inducible nitric oxide synthase.
AB  - Phenotypic modulation of smooth muscle is associated with various pathological
      conditions, including bladder dysfunction. Cytoskeletal dynamics modulate the
      cell phenotype and were recently shown to be involved in regulation of inducible
      nitric oxide synthase (iNOS). We tested the hypothesis that the cell
      differentiation status affects iNOS expression, and that iNOS is preferentially
      expressed in immature dedifferentiated bladder smooth muscle cells (BSMC).
      Isolated at BSMC were put into different stages of differentiation by serum
      deprivation on laminin-coated plates in the presence of IGF-I and by interaction
      with Rho signaling and actin polymerization. iNOS and smooth muscle-myosin heavy
      chain (SM-MHC) protein expression were investigated with Western blot analysis.
      Our results showed iNOS protein in BSMC exposed to interleukin-1 beta (2 ng/ml) +
      TNF-alpha (50 ng/ml). Growth of BSMC in serum-free medium on laminin in the
      presence of IGF-I increased SM-MHC expression, whereas cytokine-induced iNOS was
      inhibited. Disruption of F-actin with latrunculin B (0.5 microM) potentiated iNOS
      expression and decreased SM-MHC expression. Rho inhibition with C3 (2.5
      microg/ml) increased iNOS expression, whereas SM-MHC expression was slightly
      decreased. Rho-kinase inhibition with Y-27632 (10 microM) mediated a decrease in
      iNOS and a slight increase in SM-MHC expression. In conclusion, the capacity of
      BSMC to express iNOS was negatively correlated to differentiation status measured
      as SM-MHC expression. Actin cytoskeletal dynamics and Rho signaling are involved
      in regulation of cytokine-induced iNOS expression in BSMC. Phenotypic changes and
      impairment in actin cytoskeleton formation may potentiate cytokine activation and
      in turn increase nitric oxide production in the bladder during disease.

PMID- 14656767
TI  - Seasonal, tissue-specific regulation of Akt/protein kinase B and glycogen
      synthase in hibernators.
AB  - Yellow-bellied marmots (Marmota flaviventris) exhibit a circannual cycle of
      hyperphagia and nutrient storage in the summer followed by hibernation in the
      winter. This annual cycle of body mass gain and loss is primarily due to large
      scale accumulation of lipid in the summer, which is then mobilized and oxidized
      for energy during winter. The rapid and predictable change in body mass makes
      these animals ideal for studies investigating the molecular basis for body weight
      regulation. In the study described herein, we monitored seasonal changes in the
      protein levels and activity of a central regulator of anabolic metabolism, the
      serine-threonine kinase Akt-protein kinase B (Akt/PKB), during the months
      accompanying maximal weight gain and entry into hibernation (June-November).
      Interestingly, under fasting conditions, Akt/PKB demonstrated a tissue-specific
      seasonal activation. Specifically, although Akt/PKB levels did not change, the
      activity of Akt/PKB (isoforms 1/alpha and 2/beta) in white adipose tissue (WAT)
      increased significantly in July. Moreover, glycogen synthase, which lies
      downstream of Akt/PKB on a linear pathway linking the enzyme to the stimulation
      of glycogen synthesis, demonstrated a similar pattern of seasonal activation. By
      contrast, Akt/PKB activity in skeletal muscle peaked much later (i.e.,
      September). These data suggest the existence of a novel, tissue-specific
      mechanism regulating Akt/PKB activation during periods of marked anabolism.

PMID- 14656768
TI  - Electrophysiological properties of the L-type Ca(2+) current in cardiomyocytes
      from bluefin tuna and Pacific mackerel.
AB  - Tunas are capable of exceptionally high maximum metabolic rates; such capability
      requires rapid delivery of oxygen and metabolic substrate to the tissues. This
      requirement is met, in part, by exceptionally high maximum cardiac outputs,
      opening the possibility that myocardial Ca(2+) delivery is enhanced in myocytes
      from tuna compared with those from other fish. In this study, we investigated the
      electrophysiological properties of the cardiac L-type Ca(2+) channel current
      (I(Ca)) to test the hypothesis that Ca(2+) influx would be large and have faster
      kinetics in cardiomyocytes from Pacific bluefin tuna (Thunnus orientalis) than in
      those from its sister taxon, the Pacific mackerel (Scombe japonicus). In
      accordance with this hypothesis, I(Ca) in atrial myocytes from bluefin tuna had
      significantly greater peak current amplitudes and faster fast inactivation
      kinetics (-4.4 +/- 0.2 pA/pF and 25.9 +/- 1.6 ms, respectively) than those from
      mackerel (-2.7 +/- 0.5 pA/pF and 32.3 +/- 3.8 ms, respectively). Steady-state
      activation, inactivation, and recovery from inactivation were also faster in
      atrial myocytes from tuna than from mackerel. In ventricular myocytes, current
      amplitude and activation and inactivation rates were similar in both species but
      elevated compared with those of other teleosts. These results indicate enhanced
      I(Ca) in atrial myocytes from bluefin tuna compared with Pacific mackerel; this
      enhanced I(Ca) may be associated with elevated cardiac performance, because I(Ca)
      delivers the majority of Ca(2+) involved in excitation-contraction coupling in
      most fish hearts. Similarly, I(Ca) is enhanced in the ventricle of both species
      compared with other teleosts and may play a role in the robust cardiac
      performance of fishes of the family Scombridae.

PMID- 14656769
TI  - Effect of high-NaCl or high-KCl diet on hepatic Na+- and K+-receptor sensitivity
      and NKCC1 expression in rats.
AB  - We previously reported that the bumetanide-sensitive Na(+)-K(+)-2Cl-
      cotransporter (NKCC1) is involved in the hepatic Na+ and K+ sensor mechanism. In
      the present study, we examined the effects of a high-NaCl or high-KCl diet on
      hepatic Na+ and K+ receptor sensitivity and NKCC1 expression in the liver of
      Sprague-Dawley rats. RT-PCR and Western blots were used to measure NKCC1 mRNA and
      protein expression, respectively. Infusion of hypertonic NaCl or isotonic KCl +
      NaCl solutions into the portal vein increased hepatic afferent nerve activity
      (HANA) in a Na+ or K+ dose-dependent manner. After 4 wk on a high-NaCl or high
      KCl diet, HANA responses were attenuated compared with animals fed a normal diet,
      and NKCC1 expression was reduced. These results show that a high-NaCl or high-KCl
      diet decreases NKCC1 expression in the liver, and it might cause a reduction in
      hepatic Na(+)- and K(+)-receptor sensitivity.

PMID- 14656770
TI  - Effects of insulin on renal interstitial hydrostatic pressure and natriuretic
      response to volume expansion in diabetic rats.
AB  - Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood
      volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown
      to play a critical role in mediating sodium and water excretion under various
      conditions. The objective of this study was to determine the effects of immediate
      and delayed initiation of insulin treatment on the restoration of the
      relationship between RIHP, natriuretic, and diuretic responses to acute saline
      volume expansion (VE) in diabetic rats. Diabetes was induced by an
      intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups
      of female Sprague-Dawley rats were studied: normal control group (C), untreated
      diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with
      insulin for 2 wk was initiated immediately when diabetes was confirmed, which was
      2 days after STZ injection), and delayed insulin-treated diabetic group (DDI;
      treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and
      sodium and water excretions were measured before and during VE (5% body wt/30
      min) in the four groups of anesthetized rats. VE significantly increased RIHP,
      fractional excretion of sodium (FE(Na)), and urine flow rate (V) in all groups of
      rats. Basal RIHP, RIHP response to VE (Delta RIHP), and FE(Na) and V responses to
      VE (Delta FE(Na) and Delta V) were significantly lower in the D group compared
      with the C group of rats. Delta RIHP was significantly higher in both DI and DDI
      groups compared with D group but was similar to that of the C group of rats.
      While in the DI group the Delta FE(Na) response to VE was restored, Delta FE(Na)
      was significantly increased in DDI compared with D group, but it remained lower
      than that of the C group. In conclusion, insulin treatment initiated immediately
      after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and
      diuretic responses to VE; however, delayed insulin treatment restores the basal
      RIHP and RIHP response to VE but does not fully restore the natriuretic response
      to VE.

PMID- 14656771
TI  - Novel phase-shifting effects of GABAA receptor activation in the suprachiasmatic
      nucleus of a diurnal rodent.
AB  - The vast majority of neurons in the suprachiasmatic nucleus (SCN), the primary
      circadian pacemaker in mammals, contain the inhibitory neurotransmitter GABA.
      Most studies investigating the role of GABA in the SCN have been performed using
      nocturnal rodents. Activation of GABA(A) receptors by microinjection of muscimol
      into the SCN phase advances the circadian activity rhythm of nocturnal rodents,
      but only during the subjective day. Nonphotic stimuli that reset the circadian
      pacemaker of nocturnal rodents also produce phase advances during the subjective
      day. The role of GABA in the SCN of diurnal animals and how it may differ from
      nocturnal animals is not known. In the studies described here, the GABA(A)
      agonist muscimol was microinjected directly into the SCN region of diurnal
      unstriped Nile grass rats (Arvicanthis niloticus) at various times in their
      circadian cycle. The results demonstrate that GABA(A) receptor activation
      produces large phase delays during the subjective day in grass rats. Treatment
      with TTX did not affect the ability of muscimol to induce phase delays,
      suggesting that muscimol acts directly on pacemaker cells within the SCN. These
      data suggest that the circadian pacemakers of nocturnal and diurnal animals
      respond to the most abundant neurochemical signal found in SCN neurons in
      opposite ways. These findings are the first to demonstrate a fundamental
      difference in the functioning of circadian pacemaker cells in diurnal and
      nocturnal animals.

PMID- 14656772
TI  - Interleukin-6 and interleukin-15 are selectively regulated by lipopolysaccharide
      and interferon-gamma in primary pig adipocytes.
AB  - 3T3-L1 adipocytes express the lipopolysaccharide (LPS) receptor and respond to
      direct stimulation with the antigen by increasing the expression of inflammatory
      mediators. Activation of this receptor by its ligand in the macrophage causes the
      activation and translocation of nuclear factor-kappaB (NF-kappaB) to the nucleus
      where it regulates the expression of proinflammatory cytokines and other target
      genes. We investigated whether LPS could stimulate NF-kappaB translocation in
      primary pig adipocytes and regulate the expression and secretion of TNF-alpha and
      IL-6. LPS clearly induced the nuclear translocation of NF-kappaB and also
      upregulated (P < 0.05) the mRNA expression and secretion of IL-6 into the culture
      medium. An induction of TNF-alpha expression by LPS was not detected, but with
      extended incubation (8 h), there was a modest increase (P < 0.09) in the media
      concentration of this cytokine. Inhibition of either ERK1/2, PKC, or the
      inhibitory G protein (Gi) with U-0126, bisindolylmaleimide HCl, and pertussis
      toxin, respectively, blocked (P < 0.05) the increase in IL-6 expression caused by
      LPS. Because LPS administration in vivo increases circulating concentrations of
      IFN-gamma, and because this cytokine also regulates multiple immune modulators in
      the adipocyte, we also determined whether IFN-gamma regulates cytokine expression
      in primary adipocytes. Although the expression of IL-6 and TNF-alpha was
      unresponsive to IFN-gamma, the expression of IL-15 was markedly upregulated (P <
      0.01). Furthermore, the induction of IL-15 expression by IFN-gamma was blocked by
      inhibition of PKC. These data indicate that NF-kappaB is responsive to LPS in the
      adipocyte and also identify key mediators of LPS-induced IL-6 expression. In
      addition, we provide novel evidence that IFN-gamma targets the adipocyte to
      induce IL-15 expression, thus indicating a possible role for the adipocyte in the
      regulation of T-cell function and muscle metabolism during the innate immune
      response.

PMID- 14656773
TI  - Anesthesia, ethics, and severe acute respiratory syndrome.

PMID- 14656774
TI  - SARS safety and science.

PMID- 14656775
TI  - Infection control and anesthesia: lessons learned from the Toronto SARS outbreak.
AB  - PURPOSE: To describe the outbreak of severe acute respiratory syndrome (SARS) in
      Toronto, its impact on anesthesia practice and the infection control guidelines
      adopted to manage patients in the operating room (OR) and to provide emergency
      intubation outside the OR. CLINICAL FEATURES: The SARS outbreak in Toronto was
      the result of a single index patient. The causative virus, SARS-CoV, is
      moderately contagious, and is spread by droplets and contact. The virus gains
      access to host through the mucosa of the respiratory tract and the eyes. It can
      affect both healthy and compromised patients. The use of several precautionary
      measures such as goggles, gloves, gowns and facemasks and the application of
      various infection control strategies designed to minimize the spread of the virus
      are discussed. CONCLUSION: In containing the spread of SARS, vigilance and strict
      infection control are important. This results in the rediscovery of standards of
      infection control measures in daily anesthesia practice.

PMID- 14656776
TI  - Systolic pressure variation (Deltadown) can guide fluid therapy during
      pheochromocytoma surgery.
AB  - PURPOSE: To date, no monitoring has proved its usefulness for both interpretation
      and treatment of arterial hypotension following pheochromocytoma resection. In
      this prospective observational study, we measured the negative component
      (Deltadown) of the respiratory systolic pressure variation in order to assess its
      ability to guide fluid therapy in 13 patients undergoing pheochromocytoma
      surgery. METHODS: The arterial pressure waveform was recorded via a 20-g radial
      artery catheter. Deltadown was measured during abdominal exploration (baseline),
      after fluid loading, before and following tumour resection, and during treatment
      of arterial hypotension. RESULTS: At baseline, Deltadown ranged between 1 and 15
      mmHg (median: 3 mmHg). Volume loading (500 mL colloid over 20 min) performed
      during abdominal exploration significantly reduced Deltadown (P = 0.001) and
      resulted in Deltadown values </= 2 mmHg in all 13 patients. The Deltadown
      measured immediately before resection was larger in patients who had arterial
      hypotension (systolic arterial pressure (SAP) < 90 mmHg) following tumour removal
      than in other patients [4 (1-10) vs 1 (0-3) mmHg; P = 0.04]. During hypotension,
      Deltadown was greater in patients where fluid replacement restored SAP than in
      patients where fluids were ineffective and vasopressors needed [Deltadown: 4 (3
      9) vs 1 (1-2) mmHg; P = 0.03]. CONCLUSION: During pheochromocytoma surgery, a
      Deltadown </= 2 mmHg appears to indicate minimal intravascular volume depletion.
      Deltadown measurements could be used to guide fluid therapy for the prevention
      and treatment of arterial hypotension following pheochromocytoma removal.

PMID- 14656777
TI  - Rofecoxib does not compromise platelet aggregation during anesthesia and surgery.
AB  - PURPOSE: This study was undertaken because, although there is evidence that
      cyclooxygenase type 2 (COX)-2 inhibitors do not compromise platelets in healthy
      volunteers, many clinicians remain hesitant to administer them perioperatively
      without definitive evidence of intact platelet function during anesthesia and
      surgery. METHODS: In 20 patients scheduled for lower abdominal and pelvic
      surgery, 5 mL of blood were obtained for baseline platelet aggregometry. One hour
      prior to surgery, patients received an oral solution of either rofecoxib (ROF) 50
      mg or placebo (PLAC) by randomized, double-blinded assignment. Approximately one
      hour after onset of anesthesia, an intraoperative blood sample was obtained.
      Baseline and postdrug samples were centrifuged to generate platelet-rich plasma,
      which was challenged with adenosine diphosphate (ADP) and arachidonic acid (AA).
      Aggregometry was performed with and without incubation with aspirin. The data in
      each subject were normalized to baseline aggregation in response to AA alone and
      ADP alone. Intergroup differences were assessed using paired t test; P < 0.05 was
      considered significant. RESULTS: Consistent with known effects of anesthesia on
      platelet function, both groups had approximately 25% intraoperative declines in
      aggregation in response to ADP (P = NS for PLAC vs ROF) and even greater declines
      in response to AA (P = NS for PLAC vs ROF). Aspirin eliminated aggregation in
      response to AA in both groups (P = NS), and it caused similar declines in PLAC
      and ROF groups during exposure to ADP (P = NS). CONCLUSION: This study provides
      strong evidence that ROF does not compromise platelet aggregation during
      anesthesia and surgery; nor does it interfere with the platelet inhibitory effect
      of aspirin.

PMID- 14656778
TI  - Volume replacement with HES 130/0.4 may reduce the inflammatory response in
      patients undergoing major abdominal surgery.
AB  - PURPOSE: To investigate the effects of intravascular volume replacement therapy
      on the inflammatory response during major surgery. METHODS: Thirty-six patients
      scheduled for elective abdominal surgery were randomized to receive either 6%
      hydroxyethylstarch (130,000 Dalton mean molecular weight, degree of substitution
      0.4; n = 18, HES-group) or lactated Ringer's solution (RL-group; n = 18) for
      intravascular volume replacement. Fluid therapy was given perioperatively and
      continued for 48 hr in the intensive care unit. Volume replacement was guided by
      physiological parameters. Serum concentrations of interleukin (IL)-6, IL-8 and IL
      10 and soluble adhesion molecules (sELAM-1 and sICAM-1) were measured after
      induction of anesthesia, four hours after the end of surgery, as well as 24 hr
      and 48 hr postoperatively. RESULTS: Biometric and perioperative data,
      hemodynamics and oxygenation were similar between groups. On average, 4470 +/-
      340 mL of HES 130/0.4 per patient were administered in the HES-group compared to
      14310 +/- 750 mL of RL in the RL-group during the study period. Release of pro
      inflammatory cytokines IL-6 and IL-8 was significantly lower in the HES-group
      [(peak values) 47.8 +/- 12.1 pg*dL(-1) of IL-6 and 35.8 +/- 11.2 pg*mL(-1) of IL
      8 (HES-group) vs 61.2 +/- 11.2 pg*dL(-1) of IL-6 and 57.9 +/- 9.7 pg*mL(-1) of IL
      8 (RL-group); P < 0.05]. Serum concentrations of sICAM-1 were significantly
      higher in the RL-group [(peak values) 1007 +/- 152 ng*mL(-1) (RL-group) vs 687 +/
      122 ng*mL(-1), (HES group); P < 0.05)]. Values of sELAM-1 were similar in both
      groups. CONCLUSION: Intravascular volume replacement with HES 130/0.4 may reduce
      the inflammatory response in patients undergoing major surgery compared to a
      crystalloid-based volume therapy. We hypothesize that this is most likely due to
      an improved microcirculation with reduced endothelial activation and less
      endothelial damage.

PMID- 14656779
TI  - Neuromuscular block with vecuronium reduces the rapidly extracted auditory evoked
      potentials index during steady state anesthesia.
AB  - PURPOSE: During clinical monitoring, vecuronium appeared to reduce the rapidly
      extracted auditory evoked potentials index (A-line ARX index or AAI) to some
      extent. A prospective and randomized study was designed to analyze this
      phenomenon. METHODS: Forty adult patients undergoing elective surgery were
      studied. After tracheal intubation, anesthesia was maintained with an end-tidal
      isoflurane concentration (F(ET)ISO) of 1.0% for 20 min, then a 10-mL dose of
      either vecuronium 0.05 mg*kg(-1), 0.1 mg*kg(-1), 0.2 mg*kg(-1) or saline was
      administered in a randomized, double-blind design. The AAI and bispectral index
      (BI(hx)) were monitored throughout the study and analyzed off-line. RESULTS:
      BI(hx) was unaltered after the administration of saline or vecuronium. The mean
      of the averaged (per patient) AAI values recorded from two minutes to ten minutes
      after the administration of saline or vecuronium 0.05 mg*kg(-1) did not differ
      significantly from the corresponding mean recorded from 15 min to 20 min after
      F(ET)ISO maintained 1.0% (P = 0.678, 0.169), however after the administration of
      vecuronium 0.1 mg*kg(-1) or 0.2 mg*kg(-1), AAI was reduced from 18.3, 18.0 to
      14.8, 13.4 (P = 0.016, 0.017). CONCLUSIONS: Neuromuscular block with vecuronium
      reduces AAI in patients during steady state anesthesia without surgical stimuli,
      while BI(hx) is unaltered. The cut-off values of AAI for events should be
      determined according to the level of neuromuscular blockade when monitoring the
      depth of anesthesia/sedation.

PMID- 14656780
TI  - Prophylactic iv ondansetron reduces nausea, vomiting and pruritus following
      epidural morphine for postoperative pain control.
AB  - PURPOSE: To evaluate the prophylactic effect of ondansetron on nausea and
      vomiting following epidural morphine for postoperative pain control. METHODS:
      Seventy women (n = 35 in each group) undergoing abdominal total hysterectomy
      under epidural anesthesia were enrolled in this randomized, double-blinded, and
      placebo-controlled study. At the end of surgery, all patients received epidural
      morphine 3 mg for postoperative pain relief. Before morphine injection, the
      ondansetron group received iv ondansetron 4 mg, whereas the placebo group
      received iv saline. RESULTS: Patients in the ondansetron group reported a lower
      frequency of total postoperative nausea and vomiting (22%) and lower frequency of
      rescue antiemetic request (12%) than those in the placebo group (52% and 39%,
      respectively; P < 0.05). In addition, ondansetron was associated with a reduced
      incidence of pruritus following epidural morphine (28% vs 58%; P < 0.05).
      CONCLUSION: We conclude that iv ondansetron 4 mg is effective in the prevention
      of nausea, vomiting, and pruritus following epidural morphine for postoperative
      pain control.

PMID- 14656781
TI  - Mini-dose (0.05 mg) intrathecal morphine provides effective analgesia after
      transurethral resection of the prostate.
AB  - PURPOSE: To determine the optimal dose of intrathecal morphine that produces
      satisfactory analgesia with minimum side effects in elderly patients undergoing
      transurethral resection of the prostate (TURP). METHODS: In this double-blind
      prospective study, 42 patients undergoing TURP with spinal anesthesia were
      allocated to one of three groups. Group A (n = 14) received tetracaine, 10 mg,
      alone. Group B (n = 13) and Group C (n = 15) received morphine 0.05 mg and 0.10
      mg, respectively, in combination with tetracaine. Postoperative pain, nausea and
      pruritus were evaluated using visual analogue scales (VAS). SpO(2) and
      respiratory rate were also assessed. RESULTS: At three, five, seven and 24 hr
      after spinal anesthesia, the VAS scores for pain in Groups B and C were
      significantly less than in Group A. Group C experienced significantly greater VAS
      scores for pruritus as compared to Groups A and B. There was no significant
      difference in the intensity of nausea among the three groups. No patient
      experienced hypoxemia (SpO(2) < 90%) and respiratory depression (respiratory rate
      < 10 beats*min(-1)) in any group. CONCLUSION: A dose of 0.05 mg in intrathecal
      morphine with spinal anesthesia would be optimal for elderly patients undergoing
      TURP.

PMID- 14656782
TI  - Ropivacaine combined with various anti-arrhythmic drugs results in mild
      alterations in myocardial contractility in pigs.
AB  - PURPOSE: The present study was undertaken following the observation of a marked
      decrease in myocardial contractility after ropivacaine in a patient on
      amiodarone, in order to investigate the cardiovascular effects of combining
      ropivacaine with anti-arrhythmic drugs (AARD). METHODS: Anesthetized domestic
      pigs were treated with disopyramide, flecainide, atenolol, amiodarone, diltiazem
      or nicardipine at a dose leading to blood levels obtained in treated patients,
      then received 1 mg*kg(-1) ropivacaine. Blood pressure (BP), left venticular (LV)
      dP/dt max, sinus heart rate, and intraventricular conduction time were measured
      before and following the administration of AARD, and following ropivacaine at
      different time points. RESULTS: All tested AARD induced the expected hemodynamic
      and electrophysiologic effects. Following ropivacaine, a 20 to 35% decrease in LV
      dP/dt max of prolonged duration was observed with amiodarone only. A brief 10 to
      20% decrease in mean BP was observed in all animals, except those treated with
      nicardipine who sustained an important and prolonged decrease in BP. All other
      variables were not significantly affected. DISCUSSION: The combination of
      ropivacaine with AARD was always associated with a slight drop in LV dP/dt max.
      The effect on mean BP was slight, except with nicardipine. Clinicians should be
      aware of the interactions of ropivacaine with AARD, especially amiodarone and
      nicardipine.

PMID- 14656783
TI  - Best evidence in anesthetic practice: prevention: magnesium sulfate reduces the
      risk of eclampsia in women with pre-eclampsia.

PMID- 14656784
TI  - Patient-controlled analgesia with fentanyl provides effective analgesia for
      second trimester labour: a randomized controlled study.
AB  - PURPOSE: To examine dose and lockout intervals for effective fentanyl patient
      controlled analgesia (PCA) in second trimester genetic termination of pregnancy,
      and compare three different fentanyl PCA regimes with morphine PCA. METHODS: In a
      double-blind randomized study, 60 ASA physical status I-II patients received one
      of three fentanyl PCAs or morphine PCA. Labour was induced with prostaglandins
      and PCA use continued until delivery. Within two hours following delivery, four
      visual analogue scales (VAS) were administered measuring anticipated pain, pain
      relief in labour and delivery, and overall satisfaction. The drug delivery/demand
      ratio for two hours preceding delivery was obtained from the PCA pump. The
      outcome variables were analyzed using the Chi square test and analysis of
      variance as appropriate. RESULTS: The delivery/demand ratio was 0.71 +/- 0.27
      (mean +/- standard deviation) for morphine; 0.67 +/- 0.21 for fentanyl 50 micro
      g, lockout six-minute; 0.63 +/- 0.21 for fentanyl 25 micro g, lockout three
      minute; and 0.81 +/- 0.17 for fentanyl 50 micro g, lockout three-minute groups.
      We found no significant differences among the four groups with respect to using
      delivery/demand ratio as a measure of pain relief. Morphine had the highest rate
      of side effects compared to fentanyl. There was strong evidence of differences
      among groups with regard to patient satisfaction and expected pain, and moderate
      evidence of differences in the delivery and labour pain scores. CONCLUSION: This
      study found PCA fentanyl 50 micro g with a lockout period of six minutes provided
      satisfactory analgesia for second trimester labour.

PMID- 14656785
TI  - Ultrasound imaging improves learning curves in obstetric epidural anesthesia: a
      preliminary study.
AB  - PURPOSE: Epidural anesthesia may be difficult in pregnancy. We intended to
      evaluate the teaching possibilities of ultrasonography as a diagnostic approach
      to the epidural region. METHODS: Two groups of residents performed their first 60
      obstetric epidurals under supervision. One proceeded in the conventional way
      using the loss of resistance technique (control group = CG). The other group
      proceeded in the same way but was supported by prepuncture ultrasound imaging,
      giving them information about the optimal puncture point, depth and angle
      (ultrasound group = UG). Success was defined as adequate epidural anesthesia
      requiring a maximum of three attempts, reaching a visual analogue scale score of
      less than 1, while neither changing the anesthesia technique, nor starting at
      another vertebral level. In addition, intervention by the supervisor was defined
      as failure. RESULTS: In the CG we observed a success rate of 60% +/- 16% after
      the first ten attempts followed by a nearly continuous rise of the learning
      curve. Within the next 50 epidurals the rate of success increased to 84%. In the
      UG the rate of success started at 86% +/- 15%. Within 50 epidural insertions it
      rose up to a level of 94%. The difference between the two groups remained
      significant (P < 0.001). CONCLUSION: Using ultrasound imaging for teaching
      epidural anesthesia in obstetrics we found a higher rate of success during the
      first 60 attempts compared to conventional teaching. We believe this shows the
      possible value of ultrasound imaging for teaching and learning obstetric regional
      anesthesia.

PMID- 14656786
TI  - Images in Anesthesia: intrathoracic leiomyosarcoma in a parturient presenting for
      Cesarean delivery.

PMID- 14656787
TI  - Design of oxygen delivery systems influences both effectiveness and comfort in
      adult volunteers.
AB  - PURPOSE: The aim of this investigation was to compare the efficiency of four
      oxygen delivery systems in healthy volunteers. METHODS: The subjects received
      oxygen at flow rates of 3.0 and 5.0 L*min(-1) via a face mask, nasal cannulae,
      and two kinds of new open- and microphone-type oxygen delivery systems
      (OxyArm(TM) and Mike Cannula) in a random sequence, and values of partial
      arterial pressures of oxygen (PaO(2)) were measured. The comfort of these devices
      was also evaluated. RESULTS: A significant, oxygen flow dependent increase in
      PaO(2) was obtained with all devices tested. PaO(2) was significantly higher when
      the face mask was used [217.5 +/- 19.9 (mean +/- SD) mmHg at 5 L*min(-1)) than
      when the Mike Cannula was used (177.5 +/- 14.8 mmHg). The face mask was the least
      comfortable and OxyArm was the most comfortable among the devices tested.
      CONCLUSION: The results of our evaluation suggest that comfort and clinical
      performance should be considered when using oxygen delivery devices for patients
      who require oxygen supplementation.

PMID- 14656788
TI  - Transnasal jet ventilation is a useful adjunct to teach fibreoptic intubation: a
      preliminary report.
AB  - PURPOSE: Fibreoptic intubation (FOI) has become an essential technique in the
      anesthetic management of patients with difficult airways. Unfortunately,
      residents may graduate from anesthesiology training programs with insufficient
      skills in FOI. To enhance resident proficiency at FOI without compromising
      patient comfort or safety, the technique of transnasal jet ventilation-assisted
      FOI was developed. This report describes our initial experience with this
      technique. METHODS: Sixty-four patients scheduled for oromaxillofacial surgery
      under nasal endotracheal anesthesia were recruited. Twenty-eight residents at all
      levels of training performed FOI through the patient's right nostril after the
      induction of general anesthesia and neuromuscular blockade. Oxygenation and
      ventilation were maintained by a faculty anesthesiologist using a Sanders device
      to deliver a jet of oxygen through a nasal trumpet placed in the patient's left
      nostril. The time from induction until completion of the FOI was recorded.
      Residents were subsequently queried about the educational benefit of the
      technique using a standardized questionnaire. RESULTS: All residents were able to
      successfully intubate all patients in this study. Thirteen residents successfully
      performed intubations on three or more occasions with 70% performing the
      technique faster on the third trial than on the first. No evidence of hypoxemia,
      gastric distension, pneumothorax, hemodynamic instability or recall was observed.
      All respondents to the questionnaire reported that the technique was useful as an
      educational tool and recommended its use with other residents. CONCLUSION:
      Transnasal jet ventilation-assisted FOI is a useful method to train residents in
      FOI while maximizing patient comfort and safety.

PMID- 14656789
TI  - Hypercapnia increases cerebral tissue oxygen tension in anesthetized rats.
AB  - PURPOSE: To test the hypotheses that deliberate elevation of PaCO(2) increases
      cerebral tissue oxygen tension (PBrO(2)) by augmenting PaO(2) and regional
      cerebral blood flow (rCBF). METHODS: Anesthetized rats were exposed to increasing
      levels of inspired oxygen (O(2)) or carbon dioxide (CO(2); 5%, 10% and 15%, n =
      6). Mean arterial blood pressure (MAP), PBrO(2) and rCBF were measured
      continuously. Blood gas analysis and hemoglobin concentrations were determined
      for each change in inspired gas concentration. Data are presented as mean +/-
      standard deviation with P < 0.05 taken to be significant. RESULTS: The PBrO(2)
      increased in proportion to arterial oxygenation (PaO(2)) when the percentage of
      inspired O(2) was increased. Proportional increases in PaCO(2) (48.7 +/- 4.9,
      72.3 +/- 6.0 and 95.3 +/- 15.4 mmHg), PaO(2) (172.2 +/- 33.1, 191.7 +/- 42.5 and
      216.0 +/- 41.8 mmHg), and PBrO(2) (29.1 +/- 9.2, 49.4 +/- 19.5 and 60.5 +/- 23.0
      mmHg) were observed when inspired CO(2) concentrations were increased from 0% to
      5%, 10% and 15%, respectively, while arterial pH decreased (P < 0.05 for each).
      Exposure to CO(2) increased rCBF from 1.04 +/- 0.67 to a peak value of 1.49 +/-
      0.45 (P < 0.05). Following removal of exogenous CO(2), arterial blood gas values
      returned to baseline while rCBF and PBrO(2) remained elevated for over 30 min.
      The hypercapnia induced increase in PBrO(2) was threefold higher than that
      resulting from a comparable increase in PaO(2) achieved by increasing the
      inspired O(2) concentration (34.9 +/- 14.5 vs 11.4 +/- 5.0 mmHg, P < 0.05).
      CONCLUSION: These data support the hypothesis that the combined effect of
      increased CBF, PaO(2) and reduced pH collectively contribute to augmenting
      cerebral PBrO(2) during hypercapnia.

PMID- 14656790
TI  - Retrieving organs from non-heart-beating organ donors: a review of medical and
      ethical issues.
AB  - PURPOSE: The increasing gap between numbers of individuals awaiting organ
      replacement surgery and the supply of organs available for transplant underpins
      attempts to increase the number of organs available. One practice, used in other
      countries, is the recovery of organs from non-heart-beating organ donors (NHBD).
      The purpose of this review is to discuss ethical issues surrounding the use of
      organs from these donors. SOURCE: Narrative review from selected Medline
      references, and other published reports. PRINCIPAL FINDINGS: NHBD protocols have
      been established in many countries including the United States. Despite numerous
      publications, and extensive debate in the literature, significant ethical issues
      remain unresolved in the retrieval of organs from donors that have died from
      cessation of cardiac activity. The ethical concerns primarily arise in the
      determination of death, the tension between the time constraints on recovering
      organs viable for transplantation, and procedures to enhance organ viability.
      Despite a concerted effort in the United States, less than half of the organ
      procurement organizations have NHBD protocols. CONCLUSION: Canadian centres can
      learn from the difficulties encountered in other centres that have developed NHBD
      protocols. A moratorium on Canadian NHBD protocols should be considered until a
      National consensus reflecting Canadian values has been undertaken.

PMID- 14656791
TI  - Saline through the epidural needle: what volume?

PMID- 14656793
TI  - Avoiding the accidental iv injection of local anesthetics.

PMID- 14656795
TI  - Choosing a laryngoscope blade: straight vs curved.

PMID- 14656797
TI  - Choosing a laryngoscope blade: straight vs curved.

PMID- 14656799
TI  - Management of the unanticipated difficult airway using a modified sequential
      intubation technique.

PMID- 14656801
TI  - Preoperative checkout procedures for modern anesthesia machines in an emergency
      situation.

PMID- 14656802
TI  - Procalcitonin levels do not predict mortality following major abdominal surgery.

PMID- 14656803
TI  - Propofol and remifentanil without muscle relaxants in a patient with myasthenia
      gravis for emergency surgery.

PMID- 14656804
TI  - Catastrophic venous air embolus during prostatectomy in the Trendelenburg
      position.

PMID- 14656805
TI  - Prevention of nausea and vomiting after dental surgery: a comparison of small
      doses of propofol, droperidol, and metoclopramide.

PMID- 14656806
TI  - Autoradiographic distribution of 5-HT7 receptors in the human brain using
      [3H]mesulergine: comparison to other mammalian species.
AB  - 1. The main aim of this investigation was to delineate the distribution of the 5
      HT(7) receptor in human brain. Autoradiographic studies in guinea-pig and rat
      brain were also carried out in order to revisit and compare the anatomical
      distribution of 5-HT(7) receptors in different mammalian species. 2. Binding
      studies were performed in rat frontal cortex membranes using 10 nm
      [(3)H]mesulergine in the presence of raclopride (10 microm) and DOI (0.8 microm).
      Under these conditions, a binding site with pharmacological characteristics
      consistent with those of the 5-HT(7) receptors was identified (rank order of
      binding affinity values: 5-CT>5-HT>5-MeOT>mesulergine approximately
      methiothepin>8-OH-DPAT=spiperone approximately (+)-butaclamol>>imipramine
      approximately (+/-)-pindolol>>ondansetron approximately clonidine approximately
      prazosin). 3. The autoradiographic studies revealed that the anatomical
      distribution of 5-HT(7) receptors throughout the human brain was heterogenous.
      High densities were found over the caudate and putamen nuclei, the pyramidal
      layer of the CA2 field of the hippocampus, the centromedial thalamic nucleus, and
      the dorsal raphe nucleus. The inner layer of the frontal cortex, the dentate
      gyrus of the hippocampus, the subthalamic nucleus and superior colliculus, among
      others, presented intermediate concentrations of 5-HT(7) receptors. A similar
      brain anatomical distribution of 5-HT(7) receptors was observed in all three
      mammalian species studied. 4. By using [(3)H]mesulergine, we have mapped for the
      first time the anatomical distribution of 5-HT(7) receptors in the human brain,
      overcoming the limitations previously found in radiometric studies with other
      radioligands, and also revisiting the distribution in guinea-pig and rat brain.

PMID- 14656808
TI  - Missing women--revisited.

PMID- 14656807
TI  - The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in
      chronic hypoxic rats.
AB  - 1. The purpose of this study was to investigate whether a membrane-permeable
      superoxide dismutase mimetic, tempol, added either alone or in combination with
      the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary
      hypertension (PH) in chronic hypoxic rats. 2. Chronic hypobaric hypoxia (10%
      oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP),
      right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh)
      and the molsidomine metabolite SIN-1 were impaired in isolated proximal, but not
      distal pulmonary arteries, from chronic hypoxic rats. 3. Treatment with tempol
      (86 mg x kg(-1) day(-1) in drinking water) normalized RVSP and reduced right
      ventricular hypertrophy, while systemic blood pressure, lung and liver weights,
      and blunted ACh relaxation of pulmonary arteries were unchanged. 4. Treatment
      with molsidomine (15 mg x kg(-1) day(-1) in drinking water) had the same effects
      as tempol, except that liver weight was reduced, and potassium and U46619-evoked
      vasoconstrictions in pulmonary arteries were increased. Combining tempol and
      molsidomine did not have additional effects compared to tempol alone. ACh
      relaxation in pulmonary arteries was not normalized by these treatments. 5. The
      media to lumen diameter ratio of the pulmonary arteries was greater for the
      hypoxic rats compared to the normoxic rats, and was not reversed by treatment
      with tempol, molsidomine, or the combination of tempol and molsidomine. 6. We
      conclude that tempol, like molsidomine, is able to correct RVSP and reduce right
      ventricular weight in the rat hypoxic model. Functional and structural properties
      of pulmonary small arteries were little affected. The results support the
      possibility that superoxide dismutase mimetics may be a useful means for the
      treatment of PH.

PMID- 14656809
TI  - Giving aspirin and ibuprofen after myocardial infarction.

PMID- 14656810
TI  - Faecal incontinence.

PMID- 14656811
TI  - Health services research.

PMID- 14656813
TI  - Israel's occupation of Palestinian territories has damaged health, charity report
      says.

PMID- 14656814
TI  - Number of chronically hungry people is rising by 5m a year.

PMID- 14656815
TI  - New bill will regulate the retention of tissue.

PMID- 14656821
TI  - Canada supports agency criticised as an "AIDS denier".

PMID- 14656823
TI  - Large increases occur in cancers of skin and prostate.

PMID- 14656825
TI  - High court reverses police decision not to prosecute over abortion.

PMID- 14656826
TI  - Infectious diseases expert convicted over missing plague bacteria.

PMID- 14656827
TI  - Schistosomiasis initiative extended to five more countries.

PMID- 14656829
TI  - In pursuit of "humanitarian science".

PMID- 14656833
TI  - Obesity costs UK economy 2bn pounds sterling a year.

PMID- 14656835
TI  - Israeli government rejects charity's report that claims occupation has damaged
      health of Palestinians.

PMID- 14656836
TI  - Indirect comparison meta-analysis of aspirin therapy after coronary surgery.
AB  - OBJECTIVES: To evaluate the efficacy of low and medium dose aspirin therapy after
      coronary surgery by using an indirect comparison meta-analysis. DATA SOURCES:
      Systematic literature search of Medline, Embase, Cochrane controlled trials
      register, and trial register sites on the internet. STUDY SELECTION: Outcome was
      evaluated by angiography and reported as graft occlusion and rate of events in
      patients. Trials that did not include aspirin as the sole therapy or did not have
      a placebo control arm were excluded. Articles were assessed for eligibility and
      quality and grouped according to dosage. The estimated difference in effect of
      low and medium dose aspirin on graft occlusion was obtained by combining the
      estimated log relative risks of low dose with placebo and medium dose with
      placebo. RESULTS: For graft occlusion, the medium dose trials yielded a relative
      risk reduction of 45% compared with 26% for the low dose trials. The greater
      effect in the medium dose trials is summarised by a relative risk ratio of 0.74
      (95% confidence interval 0.52 to 1.06; P = 0.10) for graft occlusion and 0.81
      (0.57 to 1.16; P = 0.25) for events in patients. CONCLUSIONS: Medium dose aspirin
      may more successfully reduce graft occlusion than low dose regimens within the
      first year after coronary surgery.

PMID- 14656838
TI  - Cost effectiveness and cost utility model of public place defibrillators in
      improving survival after prehospital cardiopulmonary arrest.
AB  - OBJECTIVE: To determine the cost effectiveness and cost utility of locating
      defibrillators in all major airports, railway stations, and bus stations
      throughout Scotland. DESIGN: Economic modelling exercise with data from
      Heartstart (Scotland). Parameters used in economic model included direct costs
      derived for increased accident and emergency attendances, increased hospital bed
      days, purchase and maintenance of defibrillators, and training in their use; life
      years gained calculated from increased discharges from hospital and mean survival
      after discharge; utility (quality of life) obtained from published data.
      Sensitivity analyses tested the robustness of model. Future gains discounted at
      1.5% a year and future costs at 6%. SETTING: Whole of Scotland. SUBJECTS: Records
      of all prehospital cardiac arrests due to presumed heart disease that occurred in
      a major airport, railway, or bus station between May 1991 and March 1998 and were
      not witnessed by ambulance or medical staff. MAIN OUTCOME MEASURES: Observed
      survival to hospital admission and observed survival to discharge. Predicted
      survival calculated by applying observed survival in patients attended by
      ambulance staff within three minutes to those who waited longer. RESULTS: The
      total discounted direct costs were 18 325 pounds sterling a year. The cost per
      life year gained was 29 625 pounds sterling (49 625 dollars, 43 151 Euros) and
      the cost per quality adjusted life year (QALY) gained was pound 41 146 (68 924
      dollars, 59 932 Euros). More widespread provision of public place defibrillators
      would increase these figures. CONCLUSIONS: The cost per QALY calculated for
      public place defibrillators represents poorer value for money than some
      alternative strategies for improving survival after prehospital cardiopulmonary
      arrest, such as the use of other trained first responders. The figure exceeds the
      commonly discussed cut off levels for funding in the United Kingdom and United
      States of pound 30 000 and 50 000 dollars per QALY, respectively.

PMID- 14656837
TI  - Use of automated external defibrillator by first responders in out of hospital
      cardiac arrest: prospective controlled trial.
AB  - OBJECTIVE: To test the hypothesis that the use of an automated external
      defibrillator by police and fire fighters results in higher discharge rates for
      out of hospital cardiac arrest. DESIGN: Controlled clinical trial with initial
      random allocation of automated external defibrillators to first responders in
      four of the eight participating regions; each region switched from control to
      experimental, and vice versa, every four months. SETTING: Amsterdam and
      surroundings, the Netherlands. PARTICIPANTS: Patients with witnessed out of
      hospital cardiac arrests, identified by the emergency medical system between
      January 2000 and January 2002. MAIN OUTCOMES MEASURES: Survival to hospital
      discharge; return of spontaneous circulation; admission to hospital. RESULTS: 243
      patients (65% in ventricular fibrillation) were included in the experimental area
      and 226 patients (67% in ventricular fibrillation) in the control area. The
      median time interval between collapse and first shock was 668 seconds in the
      experimental area and 769 seconds in the control area (P < 0.001). 44 (18%)
      patients in the experimental area versus 33 (15%) patients in the control area
      were discharged (odds ratio 1.3 (95% confidence interval 0.8 to 2.2), P = 0.33),
      139 (57%) experimental versus 108 (48%) control patients had return of
      spontaneous circulation (1.5 (1.0 to 2.2), P = 0.05), and 103 (42%) experimental
      versus 74 (33%) control patients were admitted (1.5 (1.1 to 1.6), P = 0.02). The
      median delay from receipt of call to dispatch of the ambulance was 120 seconds,
      and the delay to dispatch of the first responder was 180 seconds. CONCLUSIONS:
      Use of automated external defibrillators by first responders did not
      significantly increase survival to discharge from hospital, although it did
      improve return of spontaneous circulation and admission to hospital. Improved
      dispatch procedures should increase the success of programmes of first responders
      using external defibrillators.

PMID- 14656839
TI  - Perinatal mortality in rural China: retrospective cohort study.
AB  - OBJECTIVES: To explore the use of local civil registration data to assess the
      perinatal mortality in a typical rural county in a less developed province in
      China, 1999-2000. DESIGN: Retrospective cohort study. Pregnancies in a cohort of
      women followed from registration of pregnancy to outcome of infant seven days
      after birth. SETTING: Routine family planning records in 20 rural townships in
      eastern China. SUBJECTS: 3697 pregnancies registered by the local family planning
      system during 1999. MAIN OUTCOME MEASURES: Abortions, stillbirths, early neonatal
      mortality, perinatal mortality. RESULTS: Only three cases were lost to follow up.
      The average age of the women at pregnancy was 25.9 years. Three hundred and
      twelve pregnancies were aborted and 240 ended in miscarriage (total 552, 15%).
      The perinatal mortality rate was 69 per 1000 births, the rate of stillbirth was
      24 per 1000 births, and the early neonatal mortality was 46 per 1000 live births.
      The early neonatal mortality was 29 in boys and 69 in girls per 1000 live births.
      The perinatal mortality rate increased notably with parity and was higher in
      townships having lower income per capita. CONCLUSIONS: The family planning system
      at the most local level is a useful data source for studying perinatal mortality
      in rural China. The perinatal mortality rate in the study county was higher than
      previously reported for both rural and urban areas in China. The results by
      parity and sex of the infant raise concern over the impact of the one child
      policy.

PMID- 14656840
TI  - Aspirin, ibuprofen, and mortality after myocardial infarction: retrospective
      cohort study.

PMID- 14656841
TI  - Penicillin for acute sore throat in children: randomised, double blind trial.
AB  - OBJECTIVE: To assess the effectiveness of penicillin for three days and treatment
      for seven days compared with placebo in resolving symptoms in children with sore
      throat. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: 43
      family practices in the Netherlands. PARTICIPANTS: 156 children aged 4-15 who had
      a sore throat for less than seven days and at least two of the four Centor
      criteria (history of fever, absence of cough, swollen tender anterior cervical
      lymph nodes, and tonsillar exudate). Interventions Patients were randomly
      assigned to penicillin for seven days, penicillin for three days followed by
      placebo for four days, or placebo for seven days. MAIN OUTCOME MEASURES: Duration
      of symptoms, mean consumption of analgesics, number of days of absence from
      school, occurrence of streptococcal sequelae, eradication of the initial
      pathogen, and recurrences of sore throat after six months. RESULTS: Penicillin
      treatment was not more beneficial than placebo in resolving symptoms of sore
      throat, neither in the total group nor in the 96 children with group A
      streptococci. In the groups randomised to seven days of penicillin, three days of
      penicillin, or placebo, one, two, and eight children, respectively, experienced a
      streptococcal sequela. CONCLUSION: Penicillin treatment had no beneficial effect
      in children with sore throat on the average duration of symptoms. Penicillin may,
      however, reduce streptococcal sequelae.

PMID- 14656842
TI  - Penicillin for acute sore throat in children: randomised, double blind trial.
      Commentary: More valid criteria may be needed.

PMID- 14656843
TI  - Knowledge about using auto-injectable adrenaline: review of patients' case notes
      and interviews with general practitioners.

PMID- 14656844
TI  - Introducing criteria based audit into Ugandan maternity units.
AB  - PROBLEM: Maternal mortality in Uganda has remained unchanged at 500/100 000 over
      the past 10 years despite concerted efforts to improve the standard of maternity
      care. It is especially difficult to improve standards in rural areas, where there
      is little money for improvements. Furthermore, staff may be isolated, poorly
      paid, disempowered, lacking in morale, and have few skills to bring about change.
      DESIGN: Training programme to introduce criteria based audit into rural Uganda.
      SETTING: Makerere University Medical School, Mulago Hospital (large government
      teaching hospital in Kampala), and Mpigi District (rural area with 10 small
      health centres around a district hospital). STRATEGIES FOR CHANGE: Didactic
      teaching about criteria based audit followed by practical work in own units, with
      ongoing support and follow up workshops. EFFECTS OF CHANGE: Improvements were
      seen in many standards of care. Staff showed universal enthusiasm for the
      training; many staff produced simple, cost-free improvements in their standard of
      care. LESSONS LEARNT: Teaching of criteria based audit to those providing health
      care in developing countries can produce low cost improvements in the standards
      of care. Because the method is simple and can be used to provide improvements
      even without new funding, it has the potential to produce sustainable and cost
      effective changes in the standard of health care. Follow up is needed to prevent
      a waning of enthusiasm with time.

PMID- 14656845
TI  - Adrenaline in the treatment of anaphylaxis: what is the evidence?

PMID- 14656846
TI  - Near drowning.

PMID- 14656847
TI  - Increasing the impact of health services research.

PMID- 14656848
TI  - Ethics and SARS: lessons from Toronto.

PMID- 14656849
TI  - Routinely asking women about domestic violence: seeking the causes of disease,
      not routine inquiry, is good practice.

PMID- 14656850
TI  - Routinely asking women about domestic violence: inquiry may be acceptable in
      different healthcare environments and to different women.

PMID- 14656851
TI  - Routinely asking women about domestic violence: ill considered professional
      interference in personal relationships will prove damaging.

PMID- 14656852
TI  - Management of urinary tract infections in children: no evidence exists.

PMID- 14656853
TI  - Paying for bmj.com: BMJ is the property of the world.

PMID- 14656854
TI  - Management of urinary tract infections in children: priorities need to be set.

PMID- 14656855
TI  - Paying for bmj.com: move is understandable but sad end to a decade.

PMID- 14656856
TI  - Paying for bmj.com: let the journal be innovative in maintaining information
      flows and linkages.

PMID- 14656857
TI  - Paying for bmj.com: is this measure scientific literature's half open sesame?

PMID- 14656858
TI  - Paying for bmj.com: nothing is for free.

PMID- 14656859
TI  - Paying for bmj.com: researchers will submit their articles elsewhere.

PMID- 14656860
TI  - Paying for bmj.com: move is a sensible surprise.

PMID- 14656861
TI  - Dietary fat intake and risk of stroke: association may differ with subtypes of
      ischaemic stroke.

PMID- 14656862
TI  - Dietary fat intake and risk of stroke: allegations about dietary fat are
      unfounded.

PMID- 14656864
TI  - Illiteracy is not just a historical phenomenon.

PMID- 14656865
TI  - Patients need comfort and control in beds and chairs.

PMID- 14656866
TI  - Non-commercial randomised clinical trials need money for meetings and travel
      expenses.

PMID- 14656867
TI  - A career in urology.

PMID- 14656868
TI  - A career check for medical managers.

PMID- 14656869
TI  - Life as a doctor with diabetes.

PMID- 14656870
TI  - Plasma D-dimer measurement as a predictor of venous thrombosis.

PMID- 14656871
TI  - c-kit is not expressed in Hodgkin disease and anaplastic lymphoma kinase (ALK)
      positive anaplastic large cell lymphoma.

PMID- 14656873
TI  - IgG antiplatelet immunity is dependent on an early innate natural killer cell
      derived interferon-gamma response that is regulated by CD8+ T cells.
AB  - The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic
      platelets are poorly understood. We studied the role that murine recipient CD8+ T
      and natural killer (NK) cells play in immunity against allogeneic platelets.
      BALB/c mice were depleted of the cells by cell-specific antibodies, transfused
      weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were
      measured by flow cytometry. While allogeneic platelet transfusions into wild-type
      recipients stimulated IgG antidonor antibodies in all mice by the fifth
      transfusion, CD8-depleted mice had significantly (P<.001) enhanced antibody
      production. Isotype analysis revealed that CD8+ T cells suppressed T-helper 2
      (Th2)-associated IgG1 but enhanced Th1-associated IgG2a. Compared with wild-type
      mice, platelet transfusions into CD8-depleted mice stimulated enhanced
      intracellular interferon (IFN)-gamma production by CD4- lymphocytes within 24
      hours after the first transfusion. The early IFN-gamma response correlated with
      nitric oxide-dependent splenic cytotoxicity (P<.001). In asialo ganglioside
      monosialic acid 1 (GM1)-depleted mice transfused with allogeneic platelets, the
      IFN-gamma production, splenic cytotoxicity, and IgG antidonor antibody response
      were significantly suppressed. These results demonstrate that IgG antiplatelet
      immunity is dependent on an early NK cell-derived IFN-gamma response that is
      negatively regulated by CD8+ T cells and suggest that targeting innate NK cell
      responses may significantly reduce platelet alloimmunization.

PMID- 14656874
TI  - Targeted overexpression of Bcl-XL in B-lymphoid cells results in
      lymphoproliferative disease and plasma cell malignancies.
AB  - Multiple myeloma is an incurable malignancy, and there is currently no mouse
      model that fully recapitulates the development and progression of the disease. We
      now describe a transgenic mouse that expresses a Bcl-XL transgene under the
      control of the 3'kappa immunoglobulin light chain enhancer, which is most active
      in murine B cells in late developmental stages. These mice developed nonmalignant
      plasma cell foci in the bone marrow and soft tissues and hyaline tubular casts in
      the kidneys. Median survival of the 3'KE/Bcl-XL mice was similar to littermate
      controls. When the 3'KE/Bcl-XL mouse was crossed to an Emu/c-Myc transgenic
      mouse, median survival of double transgenic progeny was 5.5 weeks. Peripheral
      blood and soft tissues were infiltrated with immature/mature B cells, and plasma
      cell lesions were identified in the bone marrow of all mice coexpressing Bcl-XL
      and c-Myc. These B- and plasma cell lesions demonstrated features consistent with
      malignancy. These results indicate that the 3'kappa immunoglobulin light chain
      enhancer can effectively target expression of Bcl-XL to B cells in late
      developmental stages, and they provide direct evidence that Bcl-XL can contribute
      to plasmacytomagenesis. Furthermore, this murine model serves as an important
      step in developing a novel genetically induced mouse model of plasma cell
      malignancies exhibiting bone marrow involvement.

PMID- 14656875
TI  - Natural history of GATA1 mutations in Down syndrome.
AB  - Acquired mutations in megakaryocyte transcription factor GATA1 have recently been
      reported in Down syndrome (DS), transient myeloproliferative disorder (TMD), and
      acute megakaryoblastic leukemia (AMKL). To provide novel insight into GATA1
      mutations in DS, genomic DNA was assayed from 12 AMKL and 4 TMD cases (including
      neonatal, prediagnosis samples in 4 of 16), neonatal blood spots from 21 DS
      children without clinically evident TMD or AMKL, and 62 non-DS cord blood
      samples, using techniques not previously employed with such samples. GATA1
      mutations were present in all TMD and AMKL cases and at birth in 3 of 4 children
      without known clinical TMD, who later developed AMKL. They were present at birth
      in 2 of 21 DS neonates, who have not yet, but could still, develop AMKL (now 26
      and 31 months). GATA1 mutations were not detected in 62 non-DS cord blood
      samples. In 4 AMKL patients multiple independent GATA1 mutations were observed.
      These data show GATA1 mutations occur in utero in most DS TMD and AMKL, that they
      may occur without clinical signs of disease, and that multiple separate GATA1
      mutant clones can occur in an individual. The findings have implications for
      pathogenesis of DS TMD and AMKL and highlight parallels between DS AMKL and other
      childhood leukemias.

PMID- 14656876
TI  - Hepcidin, a candidate modifier of the hemochromatosis phenotype in mice.
AB  - Hereditary hemochromatosis (HH) type I is a disorder of iron metabolism caused by
      a mutation in the HFE gene. Whereas the prevalence of the mutation is very high,
      its penetrance seems very low. The goal of our study was to determine whether
      hepcidin, a recently identified iron-regulatory peptide, could be a genetic
      modifier contributing to the HH phenotype. In mice, deficiency of either HFE
      (Hfe(-/-)) or hepcidin (Usf2(-/-)) is associated with the same pattern of iron
      overload observed in patients with HH. We intercrossed Hfe(-/-) and Usf2(+/-)
      mice and asked whether hepcidin deficiency increased the iron burden in Hfe(-/-)
      mice. Our results showed that, indeed, liver iron accumulation was greater in the
      Hfe(-/-)Usf2(+/-) mice than in mice lacking Hfe alone. This result, in agreement
      with recent findings in humans, provides a genetic explanation for some
      variability of the HH phenotype.

PMID- 14656877
TI  - Contributions of beta2-microglobulin-dependent molecules and lymphocytes to iron
      regulation: insights from HfeRag1(-/-) and beta2mRag1(-/-) double knock-out mice.
AB  - Genetic causes of hereditary hemochromatosis (HH) include mutations in the HFE
      gene, coding for a beta2-microglobulin (beta2m)-associated major
      histocompatibility complex class I-like protein. However, iron accumulation in
      patients with HH can be highly variable. Previously, analysis of beta2mRag1(-/-)
      double-deficient mice, lacking all beta2m-dependent molecules and lymphocytes,
      demonstrated increased iron accumulation in the pancreas and heart compared with
      beta2m single knock-out mice. To evaluate whether the observed phenotype in
      beta2mRag1(-/-) mice was due solely to the absence of Hfe or to other beta2m
      dependent molecules, we generated HfeRag1(-/-) double-deficient mice. Our studies
      revealed that introduction of Rag1 deficiency in Hfe knock-out mice leads to
      heightened iron overload, mainly in the liver, whereas the heart and pancreas are
      relatively spared compared with beta2mRag1(-/-) mice. These results suggest that
      other beta2m-interacting protein(s) may be involved in iron regulation and that
      in the absence of functional Hfe molecules lymphocyte numbers may influence iron
      overload severity.

PMID- 14656878
TI  - Differential gene expression of human stem progenitor cells derived from early
      stages of in utero human hematopoiesis.
AB  - Hematopoietic stem progenitor cells (HSPCs) are highly enriched in a rare subset
      of Lin-CD34+CD38- cells. Independent of stage of human development, HSPC function
      segregates to the subset of Lin-CD34+CD38- cells. However, fetal-derived HSPCs
      demonstrate distinct self-renewal and differentiation capacities compared with
      their adult counterparts. Here, to characterize the molecular nature of fetal
      HSPCs, suppressive subtractive hybridization was used to compare gene expression
      of HSPCs isolated from fetal blood (FB-HSPCs) versus adult mobilized peripheral
      blood (MPB-HSPCs). We identified 97 differentially expressed genes that could be
      annotated into distinct groups that include transcription factors, cell cycle
      regulators, and genes involved in signal transduction. Candidate regulators, such
      as Lim only domain-2 (LMO2), nuclear factor-kappa B (NF-kappaB), tripartite motif
      28 (Trim28), and N-myc protooncogene (MYCN), and a novel homeobox gene product
      were among transcripts that were found to be differentially expressed and could
      be associated with specific proliferation and differentiation properties unique
      to FB-HSPCs. Interestingly, the majority of genes associated with signal
      transduction belong to Ras pathway, highlighting the significance of Ras
      signaling in FB-HSPCs. Genes differentially expressed in FB-HSPCs versus adult
      MPB-HSPCs were verified using quantitative real-time polymerase chain reaction (Q
      PCR). This approach also resulted in the identification of a transcript that is
      highly expressed in FB-HSPCs but not detectable in more differentiated Lin
      CD34+CD38+ FB progenitors. Our investigation represents the first study to
      compare phenotypically similar, but functionally distinct, HSPC populations and
      to provide a gene profile of unique human HSPCs with higher proliferative
      capacity derived from early in utero human blood development.

PMID- 14656879
TI  - Bcl-XL down-regulation suppresses the tumorigenic potential of NPM/ALK in vitro
      and in vivo.
AB  - Deregulated apoptosis is a common finding in tumorigenesis. The oncogenic
      tyrosine kinase nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) delivers a
      strong survival signal in anaplastic large cell lymphomas (ALCLs). Although
      NPM/ALK activates multiple antiapoptotic pathways, the biologic relevance and
      therapeutic potential of more downstream apoptotic effectors are mostly unknown.
      In this report, the NPM/ALK-mediated induction of Bcl-XL (but not of Bcl-2) was
      identified in human ALCL-derived cells. NPM/ALK kinase activity was required to
      promote Bcl-XL expression and its protective effect on mitochondrial homeostasis.
      Down-regulation of Bcl-XL significantly reduced the antiapoptotic potential of
      NPM/ALK in both transformed murine Ba/F3 pro-B cells and human ALCL-derived
      KARPAS-299 cells. To elucidate the role of Bcl-XL in vivo, Ba/F3-NPM/ALK+ cells
      expressing a doxycycline (Dox)-inducible Bcl-XL antisense transgene (pTet-ON)
      were injected into nude mice. Doxycycline administration prevented a fatal
      systemic disease in 15 of 15 intravenously injected mice and the appearance of
      subcutaneous tumor xenografts in 9 of 12 mice; in vivo down-regulation of Bcl-XL
      was also documented. Our results show a pivotal role for Bcl-XL in ALK-mediated
      oncogenicity; a single protein placed downstream of a known oncogene can be
      crucial for the survival of neoplastic cells both in vitro and in vivo. Bcl-XL
      deserves further investigation as a possible therapeutic target in ALK+ ALCLs.

PMID- 14656880
TI  - Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX,
      and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with
      warfarin sensitivity.
AB  - We analyzed mutations of 7 vitamin K-dependent protein and cytochrome P450 2C9
      genes in 45 patients and investigated whether any contribute to the large
      interpatient variability in the warfarin dose-effect relationship. Total
      clearance and daily dose, INR and INR/Cp, were used as pharmacokinetic and
      pharmacodynamic indexes, respectively. Patients were grouped by genotype based on
      a single polymorphism and combinations of polymorphisms. Among the 30 sequence
      variants identified, CYP2C9*3, 165Thr-->Met of the factor II gene, -402G-->A, (37
      bp repeat)n, and -746T-->C of the factor VII gene, and (CAA repeat)n of the gamma
      glutamyl carboxylase gene were selected as candidate polymorphisms. As the
      analysis of single polymorphisms implied, the highest INR/Cp mean values and the
      lowest warfarin maintenance doses were observed in patients homozygous for the
      165Met, -402G, (37-bp repeat)6 and -746T alleles. Multiple regression analysis
      revealed that warfarin sensitivity was independently associated with -402G-->A,
      (CAA repeat)n, CYP2C9*3, and 165Thr-->Met, which accounted for 50% of variance.
      These results suggest that part of the considerable interpatient variation is
      attributable to genetic variation, and the combined genotyping of CYP2C9 and
      certain vitamin K-dependent protein genes is useful for predicting anticoagulant
      responses.

PMID- 14656881
TI  - Interferon consensus sequence binding protein (ICSBP; IRF-8) antagonizes BCR/ABL
      and down-regulates bcl-2.
AB  - BCR/ABL is the causative genetic aberration in chronic myelogenous leukemia
      (CML). Mice lacking expression of the interferon (IFN) consensus sequence binding
      protein (ICSBP), an IFN gamma-inducible transcription factor of the interferon
      regulatory factor (IRF) family, develop a disease similar to human CML. Mounting
      evidence suggests a role for ICSBP in the pathogenesis of CML. However, the
      underlying mechanisms are largely unknown. By stable and conditional expression
      of ICSBP in wild-type and BCR/ABL-transformed 32D cells (32D/wt and 32D/BA), we
      found that ICSBP inhibited BCR/ABL-mediated leukemogenesis in vivo. Moreover,
      ICSBP also overrode BCR/ABL-mediated morphology changes, chemotherapy, and
      imatinib resistance, as well as BCR/ABL-induced repression of differentiation.
      Some of these ICSBP effects may be explained in part by an ICSBP-mediated
      repression of bcl-2, a major antiapoptotic target of BCR/ABL, on transcriptional
      and protein level. Using reporter gene assays and electrophoretic mobility shift
      assays we identified that the bcl-2 promoter activity was inhibited by ICSBP by
      way of a fragment containing 2 characteristic ICSBP-responsive elements. An
      inverse correlation between ICSBP and bcl-2 expression was confirmed in vivo.
      Collectively, our findings suggest that ICSBP antagonizes BCR/ABL by down
      regulation of bcl-2 and implicates a central role for ICSBP in the pathogenesis
      of CML, as well as a therapeutic target to overcome drug resistance in bcl-2
      dependent tumors.

PMID- 14656882
TI  - Vdelta2-Jalpha rearrangements are frequent in precursor-B-acute lymphoblastic
      leukemia but rare in normal lymphoid cells.
AB  - The frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B
      acute lymphoblastic leukemia (precursor-B-ALL) are assumed to be mainly caused by
      Vdelta2-Jalpha rearrangements. We designed a multiplex polymerase chain reaction
      tified clonal Vdelta2-Jalpha rearrangements in 141 of 339 (41%) childhood and 8
      of 22 (36%) adult precursor-B-ALL. A significant proportion (44%) of Vdelta2
      Jalpha rearrangements in childhood precursor-B-ALL were oligoclonal. Sequence
      analysis showed preferential usage of the Jalpha29 gene segment in 54% of
      rearrangements. The remaining Vdelta2-Jalpha rearrangements used 26 other Jalpha
      segments, which included 2 additional clusters, one involving the most upstream
      Jalpha segments (ie, Jalpha48 to Jalpha61; 23%) and the second cluster located
      around the Jalpha9 gene segment (7%). Real-time quantitative PCR studies of
      normal lymphoid cells showed that Vdelta2 rearrangements to upstream Jalpha
      segments occurred at low levels in the thymus (10(-2) to 10(-3)) and were rare
      (generally below 10(-3)) in B-cell precursors and mature T cells. Vdelta2
      Jalpha29 rearrangements were virtually absent in normal lymphoid cells. The
      monoclonal Vdelta2-Jalpha rearrangements in precursor-B-ALL may serve as patient
      specific targets for detection of minimal residual disease, because they show
      high sensitivity (10(-4) or less in most cases) and good stability (88% of
      rearrangements preserved at relapse).

PMID- 14656883
TI  - VEGF-A165 augments erythropoietic development from human embryonic stem cells.
AB  - Combinations of hematopoietic cytokines and the ventral mesoderm inducer BMP-4
      have recently been shown to augment hematopoietic cell fate of human embryonic
      stem cells (hESCs) during embryoid body (EB) development. However, factors
      capable of regulating lineage commitment of hESC-derived hematopoiesis have yet
      to be reported. Here we show that vascular endothelial growth factor (VEGF-A165)
      selectively promotes erythropoietic development from hESCs. Effects of VEGF-A165
      were dependent on the presence of hematopoietic cytokines and BMP-4, and could be
      augmented by addition of erythropoietin (EPO). Treatment of human EBs with VEGF
      A165 increased the frequency of cells coexpressing CD34 and the VEGF-A165
      receptor KDR, as well as cells expressing erythroid markers. Although fetal/adult
      globins were unaffected, VEGF-A165 induced the expression of embryonic zeta
      (zeta) and epsilon (epsilon) globins, and was accompanied by expression of the
      hematopoietic transcription factor SCL/Tal-1. In addition to promoting
      erythropoietic differentiation from hESCs, the presence of VEGF-A165 enhanced the
      in vitro self-renewal potential of primitive hematopoietic cells capable of
      erythroid progenitor capacity. Our study demonstrates a role for VEGF-A165 during
      erythropoiesis of differentiating hESCs, thereby providing the first evidence for
      a factor capable of regulating hematopoietic lineage development of hESCs.

PMID- 14656884
TI  - Long-term outcome after bone marrow transplantation for severe aplastic anemia.
AB  - From January 1978 to December 2001, 133 patients with severe aplastic anemia
      (SAA) underwent non-T cell-depleted allogeneic bone marrow transplantation from
      an HLA-identical sibling donor, at the Hospital Saint Louis using either the
      combination of cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI;
      n=100) or Cy and antithymocyte globulin (ATG; n=33), as a conditioning regimen.
      With 13.6 years of follow-up, the 10-year survival estimate was 64%. Four factors
      were associated with lower survival: older age, use of Cy-TAI, any form of
      treatment prior to transplantation (either androgens or immunosuppressive
      therapy, [IST]), and grade II to IV acute graft-versus-host disease (GvHD). TAI
      was the sole factor associated with the occurrence of acute GvHD. The risk of
      cancers (15-year cumulative incidence, 10.9%) was associated with older age and
      with the use of cyclosporine as IST before transplantation. Cumulative incidences
      and risk factors of nonmalignant late effect including avascular osteonecrosis
      and late bacterial, viral, and fungal infection were also analyzed. Improved
      results using Cy-ATG as conditioning can lead to more than 90% chance of cure in
      patients with SAA. Even if, in our experience, the role of Cy-ATG versus that of
      Cy-TAI remained inextricably related to the year of transplantation, the major
      detrimental role of the GvHD disease in the long-term outcome and its relation to
      TAI supports avoidance of irradiation in the conditioning regimen. Furthermore,
      avoidance of any IST before transplantation in patients with a sibling donor is a
      prerequisite for attaining such excellent results.

PMID- 14656885
TI  - Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1
      association site phenocopies patients with X-linked thrombocytopenia.
AB  - Association of GATA-1 and its cofactor Friend of GATA-1 (FOG-1) is essential for
      erythroid and megakaryocyte development. To assess functions of GATA-1-FOG-1
      association during mouse development, we used the GATA-1 hematopoietic regulatory
      domain to generate transgenic mouse lines expressing a mutant GATA-1, which
      contains a substitution of glycine 205 for valine (V205G) that abrogates its
      association with FOG-1. We examined whether the transgenic expression of mutant
      GATA-1 rescues GATA-1 germ line mutants from embryonic lethality. In high
      expressor lines we observed that the GATA-1(V205G) rescues GATA-1-deficient mice
      from embryonic lethality at the expected frequency, revealing that excess GATA
      1(V205G) can eliminate the lethal anemia that is due to GATA-1 deficiency. In
      contrast, transgene expression comparable to the endogenous GATA-1 level resulted
      in much lower frequency of rescue, indicating that the GATA-1-FOG-1 association
      is critical for normal embryonic hematopoiesis. Rescued mice in these analyses
      exhibit thrombocytopenia and display dysregulated proliferation and impaired
      cytoplasmic maturation of megakaryocytes. Although anemia is not observed under
      steady-state conditions, stress erythropoiesis is attenuated in the rescued mice.
      Our findings reveal an indispensable role for the association of GATA-1 and FOG-1
      during late-stage megakaryopoiesis and provide a unique model for X-linked
      thrombocytopenia with inherited GATA-1 mutation.

PMID- 14656887
TI  - Aberrant expression of the MEL1S gene identified in association with
      hypomethylation in adult T-cell leukemia cells.
AB  - DNA methylation plays critical roles in the development and differentiation of
      mammalian cells, and its dysregulation has been implicated in oncogenesis. This
      study was designed to determine whether DNA hypomethylation-associated aberrant
      gene expression is involved in adult T-cell leukemia (ATL) leukemogenesis. We
      isolated hypomethylated DNA regions of ATL cells compared with peripheral blood
      mononuclear cells from a carrier by a methylated CpG-island
      amplification/representational difference analysis method. The DNA regions
      identified contained MEL1, CACNA1H, and Nogo receptor genes. Sequencing using
      sodium bisulfite-treated genomic DNAs revealed the decreased methylated CpG
      sites, confirming that this method detected hypomethylated DNA regions. Moreover,
      these hypomethylated genes were aberrantly transcribed. Among them, MEL1S, an
      alternatively spliced form of MEL1 lacking the PR (positive regulatory domain I
      binding factor 1 and retinoblastoma-interacting zinc finger protein) domain, was
      frequently transcribed in ATL cells, and the transcriptional initiation sites
      were identified upstream from exons 4 and 6. Transfection of MEL1S into CTLL-2
      cells conferred resistance against transforming growth factor beta (TGF-beta),
      suggesting that aberrant expression of MEL1S was associated with dysregulation of
      TGF-beta-mediated signaling. Although Tax renders cells resistant to TGF-beta,
      Tax could not be produced in most fresh ATL cells, in which MEL1S might be
      responsible for TGF-beta resistance. Our results suggest that aberrant gene
      expression associated with DNA hypomethylation is implicated in leukemogenesis of
      ATL.

PMID- 14656889
TI  - A dominant-negative mutant of C/EBPalpha, associated with acute myeloid
      leukemias, inhibits differentiation of myeloid and erythroid progenitors of man
      but not mouse.
AB  - The CCAAT/enhancer binding protein alpha (C/EBPalpha) is an essential
      transcription factor for granulocytic differentiation. C/EBPalpha mutations are
      found in approximately 8% of acute myeloid leukemia (AML) patients. Most of these
      mutations occur in the N-terminal coding region, resulting in a frame shift and
      the enhanced translation of a dominant-negative 30-kDa protein, which may be
      responsible for the differentiation block observed in AML. To test this
      hypothesis, we introduced a cDNA encoding an N-terminal mutated C/EBPalpha
      (mut10) into primary hematopoietic progenitors using a retroviral vector.
      Expression of mut10 in human CD34+ cord blood cells dramatically inhibited
      differentiation of both myeloid and erythroid lineages. Immunohistochemical
      analysis demonstrated coexpression of both myeloid and erythroid markers in the
      immature transformed cells. Surprisingly, mut10 did not block myelocytic
      differentiation in murine progenitors but did alter their differentiation
      kinetics and clonogenicity. Experiments were performed to confirm that the
      differential effect of mut10 on murine and human progenitors was not due to
      species-specific differences in C/EBPalpha protein sequences, expression levels,
      or inefficient targeting of relevant cells. Taken together, our results underline
      the intrinsic differences between hematopoietic controls in mouse and human and
      support the hypothesis that mutations in CEBPA are critical events in the
      disruption of myeloid differentiation in AMLs.

PMID- 14656892
TI  - G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and
      associated with enhanced Akt and differentiative, not proliferative, responses.
AB  - The granulocyte colony-stimulating factor receptor (G-CSFR) transduces
      intracellular signals for myeloid cell proliferation, survival, and
      differentiation through the recruitment of nonreceptor protein tyrosine kinases
      Lyn and janus kinase 2 (Jak2). This results in the tyrosine phosphorylation of a
      small set of positive and negative adapters and effectors. Grb2-associated binder
      2 (Gab2) is a newly described adapter molecule, preferentially expressed in
      hematopoietic cells and associated with phosphatidylinositol 3 (PI3) kinase.
      Studies suggest that Gab2 plays both positive and negative roles in cytokine
      receptor signaling. To investigate the role Gab2 plays in G-CSF receptor-mediated
      signaling, we have analyzed its activation state and correlated that with wild
      type and mutant G-CSF receptors stably expressed in the murine factor-dependent
      Ba/F3 cell lines. G-CSF-induced tyrosine phosphorylation of Gab2 occurred in the
      wild-type and single Y-to-F mutants (Y704F, Y729F, and Y744F), but not in the ADA
      and W650R loss-of-function mutants. Cells expressing truncated proximal G-CSFR,
      the tyrosine-null (Y4F) G-CSFR, or Y764F mutant receptors had decreased
      phosphorylation of Gab2. Specific inhibitors of Src kinase (PD173 and PP1) but
      not Jak2 kinase (AG490) blocked Gab2 phosphorylation. Phosphorylation of Gab2
      occurred in wild-type, but not Lyn-deficient, G-CSFR-transfected DT40 B cells.
      These data propose that Lyn, not Jak2, phosphorylates Gab2 and that maximal
      phosphorylation of Gab2 requires Y764, a Grb2-binding site. Serine
      phosphorylation of Akt, a marker of PI3-kinase activity, was detected in both
      wild-type and truncated proximal domain receptors, but not in the ADA and W650R
      mutants. Levels of phospho-Akt and phospho-extracellular signal-regulated kinase
      (phospho-ERK) were greater in proximal truncated than in wild-type G-CSFR cells,
      suggesting that Gab2 is dissociated from PI3 kinase or ERK activities.
      Overexpression of Gab2 enhanced the phosphorylation state of Akt, but not of ERK.
      This inhibited the proliferation of wild-type and truncated G-CSFR-transfected
      Ba/F3 cells and enhanced their myeloid differentiation. All together, these data
      indicate that G-CSF treatment leads to Lyn-mediated tyrosine phosphorylation of
      Gab2, which may serve as an important intermediate of enhanced Akt activity and
      myeloid differentiation, not growth/survival response.

PMID- 14656893
TI  - Possible link between unique chemokine and homing receptor expression at
      diagnosis and relapse location in a patient with childhood T-ALL.
AB  - Childhood acute lymphoblastic leukemia (ALL) is often associated with
      extramedullary infiltration by leukemic cells at diagnosis or at relapse. To
      understand the mechanisms behind the dissemination of T-cell ALL (T-ALL) cells
      this study investigated the homing receptor expression on the blast cells of 11
      pediatric T-ALL patients at diagnosis. One patient revealed a unique profile with
      high expression of the chemokine receptor CCR9 and the integrin CD103 on the T
      ALL cells. Both of these molecules are specifically associated with homing to the
      gut. This finding was clinically significant as the patient later suffered a
      relapse that was confined to the gut. Immunohistochemistry revealed that the
      leukemic cells in the gut still expressed CCR9 and colocalized with a high
      expression of the CCR9 ligand, CCL25. These findings suggest that the original
      expression of CCR9 and CD103 on the leukemic cells contributed to the relapse
      location in the gut of this patient.

PMID- 14656894
TI  - MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator
      inhibitor-1 promoter activation.
AB  - The MEK1,2 (MAPK/ERK kinase 1 and 2) pathway mediates the up-regulation of
      plasminogen activator inhibitor-1 (PAI-1) expression in vascular smooth muscle
      cells by a variety of hormones, including angiotensin II. Transfection of
      constitutively active MEKK-1, an upstream activator of the mitogen-activated
      protein (MAP) kinase pathways, was used to isolate an enhancer element located
      between -89 and -50 bp in PAI-1 promoter that was activated by MEKK-1 and
      selectively blocked by the MEK1,2 inhibitor PD98059. Mutational analysis revealed
      that the MEKK-1 response element (MRE) contained 2 cis-acting Sp1- and AP-1-like
      sequences, located between -75 to -70 and -63 to -52 bp, respectively.
      Overexpression of Sp1 enhanced MEKK-1-induced MRE promoter activity and a
      dominant-negative c-Fos blocked this Sp1 response. The combination of Sp1 and c
      Jun or c-Fos was required to activate this MRE. Angiotensin II (Ang II)
      stimulation increased c-Fos, c-Jun, and Sp1 binding to the MRE by 100-, 4.9-, and
      1.9-fold, respectively, and these responses were inhibited by PD98059 and AT1
      receptor antagonist candesartan. Intravenous Ang II infusion in rats increased
      aortic c-Fos binding to the MRE. This MRE sequence mediated a 4-fold increase of
      MEK1,2-dependent PAI-1/luciferase mRNA expression by angiotensin II stimulation.
      This report identifies the MEK1,2 response element that mediates angiotensin II
      stimulated PAI-1 promoter activation and shows that activation of this element
      requires Sp1 and AP-1 co-activation.

PMID- 14656895
TI  - Enamelin and autosomal-dominant amelogenesis imperfecta.
AB  - Dental enamel forms as a progressively thickening extracellular layer by the
      action of proteins secreted by ameloblasts. The most abundant enamel protein is
      amelogenin, which is expressed primarily from a gene on the X-chromosome (AMELX).
      The two most abundant non-amelogenin enamel proteins are ameloblastin and
      enamelin, which are expressed from the AMBN and ENAM genes, respectively. The
      human AMBN and ENAM genes are located on chromosome 4q13.2. The major secretory
      products of the human AMELX, AMBN, and ENAM genes have 175, 421, and 1103 amino
      acids, respectively, and are all post-translationally modified, secreted, and
      processed by proteases. Mutations in AMELX have been shown to cause X-linked
      amelogenesis imperfecta (AI), which accounts for 5% of AI cases. Mutations in
      ENAM cause a severe form of autosomal-dominant smooth hypoplastic AI that
      represents 1.5%, and a mild form of autosomal-dominant local hypoplastic AI that
      accounts for 27% of AI cases in Sweden. The discovery of mutations in the ENAM
      gene in AI kindreds proved that enamelin is critical for proper dental enamel
      formation and that it plays a role in human disease. Here we review how enamelin
      was discovered, what is known about enamelin protein structure, post
      translational modifications, processing by proteases, and its potentially
      important functional properties such as its affinity for hydroxyapatite and
      influence on crystal growth in vitro. The primary structures of human, porcine,
      mouse, and rat enamelin are compared, and the human enamelin gene, its structure,
      chromosomal localization, temporal and spatial patterns of expression, and its
      role in the etiology of amelogenesis imperfecta are discussed.

PMID- 14656896
TI  - Oral microbial heat-shock proteins and their potential contributions to
      infections.
AB  - The oral cavity is a complex ecosystem in which several hundred microbial species
      normally cohabit harmoniously. However, under certain special conditions, the
      growth of some micro-organisms with a pathogenic potential is promoted, leading
      to infections such as dental caries, periodontal disease, and stomatitis. The
      physiology and pathogenic properties of micro-organisms are influenced by
      modifications in environmental conditions that lead to the synthesis of specific
      proteins known as the heat-shock proteins (HSPs). HSPs are families of highly
      conserved proteins whose main role is to allow micro-organisms to survive under
      stress conditions. HSPs act as molecular chaperones in the assembly and folding
      of proteins, and as proteases when damaged or toxic proteins have to be degraded.
      Several pathological functions have been associated with these proteins. Many
      HSPs of oral micro-organisms, particularly periodontopathogens, have been
      identified, and some of their properties-including location, cytotoxicity, and
      amino acid sequence homology with other HSPs-have been reported. Since these
      proteins are immunodominant antigens in many human pathogens, studies have
      recently focused on the potential contributions of HSPs to oral diseases. The
      cytotoxicity of some bacterial HSPs may contribute to tissue destruction, whereas
      the presence of common epitopes in host proteins and microbial HSPs may lead to
      autoimmune responses. Here, we review the current knowledge regarding HSPs
      produced by oral micro-organisms and discuss their possible contributions to the
      pathogenesis of oral infections.

PMID- 14656897
TI  - Tongue movements in feeding and speech.
AB  - The position of the tongue relative to the upper and lower jaws is regulated in
      part by the position of the hyoid bone, which, with the anterior and posterior
      suprahyoid muscles, controls the angulation and length of the floor of the mouth
      on which the tongue body 'rides'. The instantaneous shape of the tongue is
      controlled by the 'extrinsic muscles' acting in concert with the 'intrinsic'
      muscles. Recent anatomical research in non-human mammals has shown that the
      intrinsic muscles can best be regarded as a 'laminated segmental system' with
      tightly packed layers of the 'transverse', 'longitudinal', and 'vertical' muscle
      fibers. Each segment receives separate innervation from branches of the
      hypoglosssal nerve. These new anatomical findings are contributing to the
      development of functional models of the tongue, many based on increasingly
      refined finite element modeling techniques. They also begin to explain the
      observed behavior of the jaw-hyoid-tongue complex, or the hyomandibular 'kinetic
      chain', in feeding and consecutive speech. Similarly, major efforts, involving
      many imaging techniques (cinefluorography, ultrasound, electro-palatography,
      NMRI, and others), have examined the spatial and temporal relationships of the
      tongue surface in sound production. The feeding literature shows localized tongue
      surface change as the process progresses. The speech literature shows extensive
      change in tongue shape between classes of vowels and consonants. Although there
      is a fundamental dichotomy between the referential framework and the
      methodological approach to studies of the orofacial complex in feeding and
      speech, it is clear that many of the shapes adopted by the tongue in speaking are
      seen in feeding. It is suggested that the range of shapes used in feeding is the
      matrix for both behaviors.

PMID- 14656898
TI  - Genes and gene polymorphisms associated with periodontal disease.
AB  - The scientific literature during the last ten years has seen an exponential
      increase in the number of reports claiming links for genetic polymorphisms with a
      variety of medical diseases, particularly chronic immune and inflammatory
      conditions. Recently, periodontal research has contributed to this growth area.
      This new research has coincided with an increased understanding of the genome
      which, in turn, has permitted the functional interrelationships of gene products
      with each other and with environmental agents to be understood. As a result of
      this knowledge explosion, it is evident that there is a genetic basis for most
      diseases, including periodontitis. This realization has fostered the idea that if
      we can understand the genetic basis of diseases, genetic tests to assess disease
      risk and to develop etiology-based treatments will soon be reality. Consequently,
      there has been great interest in identifying allelic variants of genes that can
      be used to assess disease risk for periodontal diseases. Reports of genetic
      polymorphisms associated with periodontal disease are increasing, but the
      limitations of such studies are not widely appreciated. While there have been
      dramatic successes in the identification of mutations responsible for rare
      genetic conditions, few genetic polymorphisms reported for complex genetic
      diseases have been demonstrated to be clinically valid, and fewer have been shown
      to have clinical utility. Although geneticists warn clinicians on the over
      enthusiastic use and interpretation of their studies, there continues to be a
      disparity between the geneticists and the clinicians in the emphasis placed on
      genes and genetic polymorphism associations. This review critically reviews
      genetic associations claimed for periodontal disease. It reveals that, despite
      major advances in the awareness of genetic risk factors for periodontal disease
      (with the exception of periodontitis associated with certain monogenetic
      conditions), we are still some way from determining the genetic basis of both
      aggressive and chronic periodontitis. We have, however, gained considerable
      insight into the hereditary pattern for aggressive periodontitis. Related to our
      understanding that it is autosomal-dominant with reduced penetrance comes a major
      clinically relevant insight into the risk assessment and screening for this
      disease, in that we appreciate that parents, offspring, and siblings of patients
      affected with aggressive periodontitis have a 50% risk of this disease also.
      Nevertheless, we must exercise caution and proper scientific method in the
      pursuit of clinically valid and useful genetic diagnostic tests for chronic and
      aggressive periodontitis. We must plan our research using plausible biological
      arguments and carefully avoid the numerous bias and misinterpretation pitfalls
      inherent in researching genetic associations with disease.

PMID- 14656900
TI  - Detection of the factor V Leiden mutation by a modified photo-cross-linking
      oligonucleotide hybridization assay.
AB  - BACKGROUND: Our previously developed assay for detection of the factor V Leiden
      mutation (G1691A) based on a nucleic acid photo-cross-linking technology used two
      allele-specific capture probes and six fluorescein-modified signal-generating
      reporter probes. We wished to improve the sensitivity and performance of the
      method. METHODS: We developed new reporter probes with approximately 10-fold more
      fluorescein molecules than the original probes. The single, cross-linker-modified
      capture probe was replaced by a three-probe system, separating the probe-target
      cross-linking function and the allelic differentiation function. The capture
      probe cross-linked to either or both of two flanking probes through stem
      structures at the capture-probe/flanking-probe junctions. The flanking probes
      cross-linked to target DNA through two cross-linking sites each. Genomic DNA was
      extracted from 0.2 mL of whole blood and restriction-enzyme digested to create a
      defined 677 bp target sequence. Preliminary genotype ranges were determined for
      the assay by testing of pre-typed samples. We then tested 1054 clinical samples,
      using an automated sample processor. RESULTS: The new assay had a 10-fold
      increase in signal-to-background ratio. Genotype results for 1039 of 1054
      clinical samples (98.6%) agreed with those of a PCR-based method. Of the 15
      remaining samples, 10 produced an indeterminate result outside the defined
      genotype ranges, 2 yielded insufficient signal to be genotyped, and 3 gave a
      discordant result. All 15 samples were genotyped correctly after re-extraction of
      genomic DNA and retesting. CONCLUSION: The modified photo-cross-linking assay for
      factor V Leiden detection is a sensitive non-PCR-based assay with potential for
      use in high-throughput clinical laboratories.

PMID- 14656901
TI  - Pyrosequencing of TPMT alleles in a general Swedish population and in patients
      with inflammatory bowel disease.
AB  - BACKGROUND: Interindividual differences in therapeutic efficacy in patients
      treated with thiopurines might be explained by the presence of thiopurine S
      methyltransferase (TPMT) alleles that encode for reduced TPMT enzymatic activity.
      It is therefore of value to know an individual's inherent capacity to express
      TPMT. METHOD: We developed a pyrosequencing method to detect 10 single-nucleotide
      polymorphisms (SNPs) in TPMT. A Swedish population (n = 800) was examined for
      TPMT*3A, TPMT*3B, TPMT*3C, and TPMT*2. Patients with inflammatory bowel disease
      (n = 24) and healthy volunteers (n = 6), selected on the basis of TPMT enzymatic
      activity, were investigated for all 10 SNPs to determine the relationship between
      TPMT genotype and phenotype. RESULTS: In the general population we identified the
      following genotypes with nonfunctional alleles: TPMT*1/*3A (*3A allelic
      frequency, 3.75%), TPMT*1/*3C (*3C allelic frequency, 0.44%), TPMT*1/*3B (*3B
      allelic frequency, 0.13%), and TPMT*1/*2 (*2 allelic frequency, 0.06%). All nine
      individuals with normal enzymatic activity were wild-type TPMT*1/*1. Thirteen
      individuals with intermediate activity were either TPMT*1/*3A (n = 12) or
      TPMT*1/*2 (n = 1). Eight individuals with low enzymatic activity were TPMT*3A/*3A
      (n = 4), TPMT*3A/*3C (n = 2), or TPMT*1/*3A (n = 2). CONCLUSION: Next to wild
      type, the most frequent alleles in Sweden are TPMT*3A and TPMT*3C. A previously
      established phenotypic cutoff for distinguishing normal from intermediate
      metabolizers was confirmed. To identify the majority of cases (90%) with low or
      intermediate TPMT activity, it was sufficient to analyze individuals for only 3
      of the 10 SNPs investigated. Nevertheless, this investigation indicates that
      other mutations might be of relevance for decreased enzymatic activity.

PMID- 14656902
TI  - Liquid chromatography-tandem mass spectrometry assay for simultaneous measurement
      of estradiol and estrone in human plasma.
AB  - BACKGROUND: Estradiol (E2) and estrone (E1) measurements form an integral part of
      the assessment of female reproductive function and have expanding roles in other
      fields. However, many E1 and E2 immunoassays have limited functional sensitivity,
      suffer from cross-reactivity, and display poor intermethod agreement. To overcome
      these problems, we developed a sensitive liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) assay for the simultaneous measurement of E1 and E2.
      METHODS: After dansyl chloride derivatization, samples were separated by fast
      gradient chromatography and injected into a tandem mass spectrometer after
      formation of positive ions with atmospheric pressure chemical ionization. The
      limits of detection and quantification, recovery, linearity, precision, and
      reference intervals were determined, and performance was compared with several
      immunoassays. RESULTS: Total run time per sample was 5 min. The multiple-reaction
      monitoring ion pairs were m/z 506/171 for 3-dansyl-estradiol and m/z 504/171 for
      3-dansyl-estrone. The limits of detection for E1 and E2 were 12.9 pmol/L (3.5
      ng/L) and 10.3 pmol/L (2.8 ng/L), respectively. Interassay imprecision (CV) was 4
      20% (n = 20). The limits of quantification (functional sensitivities) for E1 and
      E2 were 44.1 pmol/L (11.9 ng/L) and 23.2 pmol/L (6.3 ng/L), respectively. The
      assay was linear to >2200 pmol/L ( approximately 600 ng/L) for each analyte.
      Recoveries were 93-108% for E1 and 100-110% for E2. No cross-reactivity was
      observed. Method comparison with several immunoassays revealed that the latter
      were inaccurate and prone to interferences at low E1 and E2 concentrations.
      CONCLUSIONS: LC-MS/MS allows rapid, simultaneous, sensitive, and accurate
      quantification of E1 and E2 in human serum.

PMID- 14656903
TI  - Quantification of serum and urinary S-adenosylmethionine and S
      adenosylhomocysteine by stable-isotope-dilution liquid chromatography-mass
      spectrometry.
AB  - BACKGROUND: We have developed an assay that uses stable-isotope-dilution liquid
      chromatography-mass spectrometry to assess S-adenosylmethionine (SAM) and S
      adenosylhomocysteine (SAH) in body fluids to investigate the relationship of
      these metabolites to hyperhomocysteinemia. METHODS: Commercially obtained SAM
      (D(3) methyl) and (13)C(5)-SAH uniformly labeled in the adenosyl moiety, which
      was synthesized using S-adenosylhomocysteine hydrolase, were added to samples
      followed by perchloric acid protein precipitation, C(18) chromatography, and
      analysis by liquid chromatography-mass spectrometry with quantification by
      comparison of the areas of internal standard and endogenous peaks. RESULTS:
      Estimates of intraassay imprecision (CV) were 5% and 17% for SAM and SAH,
      respectively (n = 10). SAM decreased and SAH increased in serum and plasma
      samples at both 4 degrees C and room temperature over 80 h. SAM and SAH were
      unstable in samples stored longer than 2 years at -20 degrees C. In 48
      volunteers, the estimated reference intervals [from mean (2 SD) of log
      transformed data] for serum SAM and SAH were 71-168 and 8-26 nmol/L,
      respectively. Fractional excretion of SAM was higher than that of SAH, and the
      urinary SAM:SAH ratio was much higher than the serum or erythrocyte SAM:SAH
      ratios. CONCLUSIONS: Stable-isotope-dilution liquid chromatography-mass
      spectrometry can be used to quantify SAM and SAH in biological fluids and
      tissues. Sample handling and storage must be stringently controlled for any
      epidemiologic or clinical use of such assays.

PMID- 14656904
TI  - Evaluation of imprecision for cardiac troponin assays at low-range
      concentrations.
AB  - BACKGROUND: The European Society of Cardiology/American College of Cardiology
      Committee for the Redefinition of Myocardial Infarction (MI) has recommended that
      an increased cardiac troponin should be defined as a measurement above the 99th
      percentile value of the reference group. A total imprecision (CV) at the decision
      limit of </=10% is recommended. However, peer-reviewed data on assay imprecision
      are lacking. The purpose of this study was to construct the clinically relevant
      imprecision profiles for each of the commercially available cardiac troponin
      assays. Pools of human sera containing cardiac troponin concentrations around the
      MI decision limit were assessed to identify the lowest concentration associated
      with a 10% CV. METHODS: Eight serum pools targeting different concentrations of
      cardiac troponin (I and T) were prepared and stored at -70 degrees C until usage.
      The cardiac troponin measurement protocol consisted of two replicates per
      specimen per run, and one run per day for 20 days, using two reagent lots and
      three calibrations. Manufacturers of each cardiac troponin assay directly
      performed the measurements. Data analysis for each assay was centralized and
      performed according to the NCCLS EP5-A guideline. RESULTS: The lowest
      concentrations (microg/L) providing a 10% CV were as follows: AxSYM, 1.22;
      ACS:180, 0.37; Centaur, 0.33; Immuno 1, 0.34; Access, 0.06; Vidas, 0.36; Liaison,
      0.065; Dimension, 0.26; Opus, 0.90; Stratus CS, 0.10; Immulite, 0.32; Vitros ECi,
      0.44; Elecsys, 0.04; AIA 21, 0.09. CONCLUSION: No cardiac troponin assay was able
      to achieve the 10% CV recommendation at the 99th percentile reference limit
      defined by the manufacturer.

PMID- 14656905
TI  - Improved specificity of newborn screening for congenital adrenal hyperplasia by
      second-tier steroid profiling using tandem mass spectrometry.
AB  - BACKGROUND: Newborn screening for congenital adrenal hyperplasia (CAH) involves
      measurement of 17alpha-hydroxyprogesterone (17-OHP), usually by immunoassay.
      Because this testing has been characterized by high false-positive rates, we
      developed a steroid profiling method that uses liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) to measure 17-OHP, androstenedione, and cortisol
      simultaneously in blood spots. METHODS: Whole blood was eluted from a 4.8-mm
      (3/16-inch) dried-blood spot by an aqueous solution containing the deuterium
      labeled internal standard d(8)-17-OHP. 17-OHP, androstenedione, and cortisol were
      extracted into diethyl ether, which was subsequently evaporated and the residue
      dissolved in LC mobile phase. This extract was injected into a LC-MS/MS equipped
      with pneumatically assisted electrospray. The steroids were quantified in the
      selected-reaction monitoring mode by use of peak areas in reference to the stable
      isotope-labeled internal standard. We analyzed 857 newborn blood spots, including
      14 blood spots of confirmed CAH cases and 101 of false-positive cases by
      conventional screening. RESULTS: Intra- and interassay CVs for 17-OHP were 7.2
      20% and 3.9-18%, respectively, at concentrations of 2, 30, and 50 microg/L. At a
      cutoff for 17-OHP of 12.5 microg/L and a cutoff of 3.75 for the sum of peak areas
      for 17-OHP and androstenedione divided by the peak area for cortisol, 86 of the
      101 false-positive samples were within reference values by LC-MS/MS, whereas the
      742 normal and 14 true-positive results obtained by conventional screening were
      correctly classified. CONCLUSION: Steroid profiling in blood spots can identify
      false-positive results obtained by conventional newborn screening for CAH.

PMID- 14656906
TI  - Strategies for developing biomarkers of heart failure.
AB  - BACKGROUND: Heart failure (HF) is a devastating disease with increasing
      prevalence in elderly populations. One-half of all patients die within 5 years of
      diagnosis. The annual cost of treating patients with HF in the US is more than
      $20 billion, which is estimated to be greater than that of myocardial infarction
      and all cancers combined. Given the complex pathophysiology and varied
      manifestations of HF, interest has intensified in developing biological markers
      to predict susceptibility and aid in the early diagnosis and management of this
      disease. METHODS: We searched Medline via Ovid for studies published during the
      period 1966-2003 regarding various biomarkers suggested for HF. Our review
      focused on developing strategies for discovering and using new biomarkers,
      particularly those potentially linked to pathophysiologic mechanisms. We also
      point out strategic advantages, limitations, and methods available for measuring
      each of the currently proposed markers. RESULTS: Biomarkers reviewed include
      those released from the heart during normal homeostasis (natriuretic peptides),
      those produced elsewhere that act on the heart (endogenous cardiotonic steroids
      and other hormones), and those released in response to tissue damage
      (inflammatory cytokines). The concept of using a combination of multiple markers
      based on diagnosis, prognosis, and acute vs chronic disease is also discussed. In
      view of recent advances in our understanding of molecular biochemical
      derangements observed during cardiac failure, we consider the concept of
      myocardial remodeling and the heart as part of an endocrine system as strategies.
      CONCLUSION: Strategically, biomarkers linked to mechanisms involved in the
      etiology of HF, such as dysregulation of ion transport, seem best suited for
      serving as early biological markers to predict and diagnose disease, select
      therapy, or assess progression.

PMID- 14656907
TI  - Acute pulmonary embolism: part I: epidemiology, pathophysiology, and diagnosis.

PMID- 14656908
TI  - Recommendations of the National Heart, Lung, and Blood Institute Nanotechnology
      Working Group.
AB  - Recent rapid advances in nanotechnology and nanoscience offer a wealth of new
      opportunities for diagnosis and therapy of cardiovascular, pulmonary, and
      hematologic diseases and sleep disorders. To review the challenges and
      opportunities offered by these nascent fields, the National Heart, Lung, and
      Blood Institute convened a Working Group on Nanotechnology. Working Group
      participants discussed the various aspects of nanotechnology and its applications
      to heart, lung, blood, and sleep (HLBS) diseases. This report summarizes their
      discussions according to scientific opportunities, perceived needs and barriers,
      specific disease examples, and recommendations on facilitating research in the
      field. An overarching recommendation of the Working Group was to focus on
      translational applications of nanotechnology to solve clinical problems. The
      Working Group recommended the creation of multidisciplinary research centers
      capable of developing applications of nanotechnology and nanoscience to HLBS
      research and medicine. Centers would also disseminate technology, materials, and
      resources and train new investigators. Individual investigators outside these
      centers should be encouraged to conduct research on the application of
      nanotechnology to biological and clinical problems. Pilot programs and
      developmental research are needed to attract new investigators and to stimulate
      creative, high-impact research. Finally, encouragement of small businesses to
      develop nanotechnology-based approaches to clinical problems was considered
      important.

PMID- 14656909
TI  - Images in cardiovascular medicine. Approaching cardiac development in three
      dimensions by magnetic resonance microscopy.

PMID- 14656911
TI  - Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells
      to infarct borders in Swine.
AB  - BACKGROUND: The local environment of delivered mesenchymal stem cells (MSCs) may
      affect their ultimate phenotype. MR fluoroscopy has the potential to guide
      intramyocardial MSC injection to desirable targets, such as the border between
      infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2)
      navigate injection catheters to preselected targets, (3) inject safely even into
      fresh infarcts, and (4) confirm injection success immediately. METHODS AND
      RESULTS: A 1.5-T MRI scanner was customized for interventional use, with rapid
      imaging, independent color highlighting of catheter channels, multiple-slice 3D
      rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver
      coils were incorporated into guiding catheters and injection needles. These
      devices were tested for heating and used for targeted MSC delivery. In infarcted
      pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging
      included both saturation preparation MRI after intravenous gadolinium and wall
      motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter
      navigation and multiple cell injections were performed entirely with MR
      fluoroscopy at 8 frames/s with 1.7x3.3x8-mm voxels. Infarct-enhanced MR
      fluoroscopy permitted excellent delineation of infarct borders. All injections
      were safely and successfully delivered to their preselected targets, including
      infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on
      delivery in vivo and post mortem. CONCLUSIONS: Precise targeted delivery of
      potentially regenerative cellular treatments to recent myocardial infarction
      borders is feasible with an MR catheter delivery system. MR fluoroscopy permits
      visualization of catheter navigation, myocardial function, infarct borders, and
      labeled cells after injection.

PMID- 14656912
TI  - Coronary microvascular endothelial stunning after acute pressure overload in the
      conscious dog is caused by oxidant processes: the role of angiotensin II type 1
      receptor and NAD(P)H oxidase.
AB  - BACKGROUND: Few studies have examined the effect of acute pressure overload on
      endothelial function in the coronary microcirculation. METHODS AND RESULTS: In
      instrumented conscious dogs with heart rate held constant, veratrine caused a
      cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3
      mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the
      ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm
      Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1
      mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial
      stunning [ES]). Nitrite production from isolated coronary microvessels during ES
      was not different from normal. Ascorbic acid (AA), losartan, or apocynin
      prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in
      vitro in response to bradykinin with preincubation of angiotensin II for 30
      minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a
      concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(
      8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%),
      losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2
      was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable
      superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA,
      tempol, losartan, or apocynin. CONCLUSIONS: Endothelial stunning is caused by
      oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase
      by increased angiotensin II plays an important role in this process.

PMID- 14656913
TI  - Randomized comparison between stenting and off-pump bypass surgery in patients
      referred for angioplasty.
AB  - BACKGROUND: Stenting improves cardiac outcome in comparison with balloon
      angioplasty. Compared with conventional surgery, off-pump bypass surgery on the
      beating heart without cardiopulmonary bypass may reduce morbidity, hospital stay,
      and costs. The purpose, therefore, was to compare cardiac outcome, quality of
      life, and cost-effectiveness 1 year after stenting and after off-pump surgery.
      METHODS AND RESULTS: Patients referred for angioplasty (n=280) were randomly
      assigned to stenting (n=138) or off-pump bypass surgery. At 1 year, survival free
      from stroke, myocardial infarction, and repeat revascularization was 85.5% after
      stenting and 91.5% after off-pump surgery (relative risk, 0.93; 95% CI, 0.86 to
      1.02). Freedom from angina was 78.3% after stenting and 87.0% after off-pump
      surgery (P=0.06). Quality-adjusted lifetime was 0.82 year after stenting and 0.79
      year after off-pump surgery (P=0.09). Hospital stay after the initial procedure
      was 1.43 and 5.77 days, respectively (P<0.01). Stenting reduced overall costs by
      2933 dollars (26.2%) per patient (8276 dollars versus 11 209 dollars; P<0.01).
      Stenting was more cost-effective in 95% of the bootstrap estimates. CONCLUSIONS:
      At 1 year, stenting was more cost-effective than off-pump surgery while
      maintaining comparable cardiac outcome and quality of life. Stenting rather than
      off-pump surgery, therefore, can be recommended as a first-choice
      revascularization strategy in selected patients.

PMID- 14656914
TI  - No-reflow phenomenon persists long-term after ischemia/reperfusion in the rat and
      predicts infarct expansion.
AB  - BACKGROUND: No-reflow after reperfusion therapy for myocardial infarction is a
      strong predictor of clinical outcome. But its fate on a long-term basis and
      potential significance for infarct healing are not yet known. METHODS AND
      RESULTS: Twenty-nine female Fisher rats were subjected to 60 minutes of coronary
      occlusion followed by reperfusion. At 4 weeks, 15 survivors were euthanized after
      measurement of regional myocardial blood flow (radioactive microspheres) and in
      vivo staining of perfused tissue (0.5 mL 50% Uniperse blue IV). Infarct size
      (34.3+/-3.4%), scar thickness (1.19+/-0.10 mm), and infarct expansion index
      (0.51+/-0.04) were assessed from histological sections (2 additional exclusions
      because of failed occlusion). Regional myocardial blood flow in the reperfused
      infarct was reduced significantly compared with noninfarcted tissue (1.98+/-0.47
      versus 4.55+/-0.86 mL x min(-1) x g(-1), P<0.003, apical slice, and 1.77+/-0.44
      versus 5.34+/-0.38 mL x min(-1) x g(-1), P<0.0001, second slice), accompanied by
      a striking reduction of perfused capillaries within the infarct (n=23+/-4 versus
      163+/-8 in the noninfarcted tissue, P<0.0001, microscopically assessed as
      capillaries containing blue particles per high-power field). Macroscopically, no
      reflow areas were visible in 9 of 13 hearts. The number of perfused capillaries
      within the infarct correlated significantly with infarct expansion index (r=
      0.76, P<0.003), infarct thickness (r=0.60, P<0.03), and the ratio of infarct to
      septum thickness (r=0.74, P<0.004). CONCLUSIONS: The no-reflow phenomenon
      persists for 1 month after reperfusion and predicts worse scar thinning and
      infarct expansion. Thus, one might shift the "open-artery" hypothesis downstream
      to an "open-microvessel" hypothesis, relating infarct healing, infarct expansion,
      and outcome to the completeness of microvascular reperfusion above and beyond
      epicardial artery patency.

PMID- 14656915
TI  - Toll-like receptor-2 modulates ventricular remodeling after myocardial
      infarction.
AB  - BACKGROUND: Toll-like receptors (TLRs) are members of the interleukin-1 receptor
      family and transduce similar signals as interleukin-1 receptor in response to
      exogenous pathogens. Recent studies have demonstrated that TLRs are activated by
      endogenous signals, such as heat shock proteins and oxidative stress, that may
      contribute to ventricular remodeling after myocardial infarction. In this study,
      we determined whether TLR-2 was involved in cardiac remodeling after myocardial
      infarction. METHODS AND RESULTS: Myocardial infarction was induced by surgical
      left anterior descending coronary artery ligation on wild-type (WT) mice and TLR
      2-knockout (KO) mice. The survival rate was significantly higher in KO mice than
      in WT mice 4 weeks after myocardial infarction (65% versus 43%, P<0.03). Infarct
      size and degree of inflammatory cell infiltration in infarct area were similar
      between WT and KO mice. However, myocardial fibrosis in the noninfarct area of KO
      mice was much less than in WT mice (P<0.01) and was accompanied by reduced
      transforming growth factor-beta1 and collagen type 1 mRNA expressions (P<0.01 and
      P<0.05, respectively). Left ventricular dimensions at end diastole were smaller
      in KO mice than in WT mice at 1 week (P<0.05) and 4 weeks (P<0.01) after surgery.
      Furthermore, fractional shortening was higher (27.7+/-2.5% versus 21.2+/-2.6%,
      P<0.05, at 1 week, and 24.3+/-2.0% versus 16.6+/-2.5%, P<0.01, at 4 weeks) in KO
      mice compared with WT mice. CONCLUSIONS: These data suggest that TLR-2 plays an
      important role in ventricular remodeling after myocardial infarction.

PMID- 14656916
TI  - Pharmacological modulation of cardiac gap junctions to enhance cardiac
      conduction: evidence supporting a novel target for antiarrhythmic therapy.
AB  - BACKGROUND: Disease-induced alterations of cardiac gap junctions lead to
      intercellular uncoupling, which is an important mechanism of arrhythmogenesis.
      Therefore, drugs that selectively open gap junctions potentially offer a novel
      strategy for antiarrhythmic therapy. Because the peptide ZP123 was found to
      increase conductance between paired myocytes, we hypothesized that ZP123 would
      suppress acidosis-induced gap junction closure in the intact heart. METHODS AND
      RESULTS: High-resolution optical mapping was used to measure conduction velocity
      (CV) and action potential duration from ventricular epicardium of Langendorff
      perfused guinea pig hearts at baseline (pH 7.4) and during 45 minutes of
      perfusion with acidotic (pH 6.0) Tyrode's solution with (n=8) and without
      (control, n=7) ZP123 (80 nmol/L). Acidosis produced conduction slowing transverse
      (29.1+/-0.1 to 16.8+/-0.2 cm/s, P<0.0001) and longitudinal (47.2+/-2.4 to 33.2+/
      4.8 cm/s, P<0.0001) to cardiac fibers. Importantly, ZP123 inhibited conduction
      slowing during acidosis by approximately 60%. The peak effect of ZP123 was
      achieved after 16 minutes of acidosis, consistent with inhibition of uncoupling.
      ZP123 did not affect Na+ current in isolated myocytes, additionally affirming
      that preservation of CV was attributable to the compound's action on gap
      junctions. ZP123 had no effect on CV in the absence of acidosis, suggesting that
      drug activity targets gap junctions under metabolic stress. Action potential
      duration heterogeneity was significantly reduced by ZP123 (6.7+/-0.8 ms) compared
      with controls (9.7+/-3.1 ms, P<0.05), presumably by enhancing cell-to-cell
      coupling. CONCLUSIONS: These data suggest that ZP123 significantly attenuates gap
      junction closure during acidosis. Preservation of intercellular coupling
      diminished CV slowing and heterogeneous repolarization, eliminating
      arrhythmogenic substrates.

PMID- 14656917
TI  - Catheter ablation of ventricular fibrillation in rabbit ventricles treated with
      beta-blockers.
AB  - BACKGROUND: A therapeutic implication of the focal-source hypothesis of
      ventricular fibrillation (VF) is that VF can be terminated by focal ablation. We
      hypothesize that beta-adrenergic receptor blockade converts multiple-wavelet VF
      to focal-source VF and that this focal source is located near the papillary
      muscle (PM). METHODS AND RESULTS: We used optical mapping techniques to study the
      effects of propranolol (0.3 mg/L) on VF dynamics in Langendorff-perfused rabbit
      hearts. The left ventricular (LV) anterior wall was mapped and optical action
      potential duration restitution (APDR) was determined at 25 epicardial sites. We
      performed ablation during VF of the left anterior PM in hearts with (N=6) or
      without (N=6) cytochalasin infusion, the LV lateral epicardium (Epi group, N=3),
      and the LV endocardium (Endo group, N=3). The PM was also ablated in 3 hearts
      without propranolol (control group). Propranolol converted multiple-wavelet VF to
      slow VF with reentry localized to the PM. Propranolol decreased the maximal slope
      of the APDR curve (P<0.001) as well as its spatial heterogeneity (P<0.01) and
      conduction velocity (P=0.01) while increasing the VF cycle length (P<0.001). PM
      ablation terminated VF during propropranolol infusion with (6 of 6, 100%) or
      without (4 of 6, 67%) cytochalasin D and significantly reduced inducibility. VF
      did not terminate in the Epi, Endo, and control groups (P<0.001). CONCLUSIONS:
      Propranolol flattens the APDR curve and reduces conduction velocity, converting
      multiple-wavelet VF into VF with a focal source anchored to the PM. Ablation of
      this focal source may terminate VF.

PMID- 14656918
TI  - Role of the posterior left atrium and pulmonary veins in human lone atrial
      fibrillation: electrophysiological and pathological data from patients undergoing
      atrial fibrillation surgery.
AB  - BACKGROUND: Surgery can eliminate atrial fibrillation (AF), but data confirming
      the rationale for specific lesion sets are lacking. We used postoperative
      electrophysiological studies to test the rationale and effects of operative
      pulmonary venous isolation. METHODS AND RESULTS: Fourteen patients undergoing
      surgical pulmonary venous isolation for drug-refractory lone AF were studied.
      Successful isolation was confirmed postoperatively in 13 of 14 patients.
      Spontaneous sustained AF was recorded from the isolated pulmonary venous region
      (PVR) in 4 and was induced by extrastimulus testing in another. The remaining
      atrial region (RAR) was in sinus rhythm in 13 patients and nonsustained AF in 1.
      Atrial extrastimulus testing and burst pacing in the RAR failed to induce
      sustained AF. In follow-up, 1 patient developed paroxysmal AF, and electrical
      continuity between the PVR and RAR was confirmed. Isolation was achieved with
      radiofrequency ablation with no further AF. Another patient developed typical
      atrial flutter that required ablation. AF has not recurred in any patient at
      25.1+/-11.9 months (range, 6 to 56 months) after surgery. Atrial histopathology
      was consistent with tachycardia-induced changes. CONCLUSIONS: Total electrical
      isolation of the PVR controlled AF with excellent clinical outcome and appeared
      necessary for success. The isolated PVR can sustain spontaneous or induced AF,
      whereas the considerably larger RAR does not. These data provide a sound
      rationale for PVR in eliminating AF.

PMID- 14656919
TI  - Endothelial replacement and angiogenesis in arteriosclerotic lesions of
      allografts are contributed by circulating progenitor cells.
AB  - BACKGROUND: Endothelial regeneration and angiogenesis in the intima of the
      arterial wall are key events in the pathogenesis of transplantation
      arteriosclerosis. The traditional hypothesis that damaged endothelial cells are
      replaced by remaining cells of the donor vessel has been challenged by recent
      observations, but the cell origins of large arteries and microvessels are still
      not well established. METHODS AND RESULTS: Aortic segments were allografted
      between Balb/c and TIE2-LacZ (C57BL/6) mice expressing beta-galactosidase (gal)
      in endothelial cells. beta-gal+ cells in TIE2-LacZ vessels grafted to Balb/c mice
      completely disappeared, whereas the positive cells found in Balb/c aorta
      allografted into TIE2-LacZ mice 4 weeks after surgery indicated a host origin. En
      face analysis of allograft vessels displayed a unique distribution of beta-gal+
      cells on the surface at 3 days, 1 week, and 4 weeks. Interestingly, 35+/-19% beta
      gal+ cells were found in arterial segments allografted into chimeric mice with
      TIE2-LacZ bone marrows. Furthermore, endothelial cells of microvessels within
      allografts had a beta-gal+ staining in the media at 1 week and in the neointimal
      lesions and adventitia at 4 weeks. Allograft studies in chimeric mice
      demonstrated that beta-gal+ cells of microvessels in transplant arteriosclerosis
      were derived from bone marrow progenitors. CONCLUSIONS: We provide strong
      evidence that endothelial cells of neointimal lesions in allografts are derived
      from circulating progenitor cells and that bone marrow-derived progenitors are
      responsible for angiogenesis of the allograft, that is, the formation of
      microvessels in transplant arteriosclerosis.

PMID- 14656920
TI  - Cardiac-specific overexpression of fibroblast growth factor-2 protects against
      myocardial dysfunction and infarction in a murine model of low-flow ischemia.
AB  - BACKGROUND: Preconditioning the heart before an ischemic insult has been shown to
      protect against contractile dysfunction, arrhythmias, and infarction.
      Pharmacological studies have suggested that fibroblast growth factor-2 (FGF2) is
      involved in cardioprotection. However, because of the number of FGFs expressed in
      the heart and the promiscuity of FGF ligand-receptor interactions, the specific
      role of FGF2 during ischemia-reperfusion injury remains unclear. METHODS AND
      RESULTS: FGF2-deficient (Fgf2 knockout) mice and mice with a cardiac-specific
      overexpression of all 4 isoforms of human FGF2 (FGF2 transgenic [Tg]) were
      compared with wild-type mice to test whether endogenous FGF2 elicits
      cardioprotection. An ex vivo work-performing heart model of ischemia was
      developed in which murine hearts were subjected to 60 minutes of low-flow
      ischemia and 120 minutes of reperfusion. Preischemic contractile function was
      similar among the 3 groups. After ischemia-reperfusion, contractile function of
      Fgf2 knockout hearts recovered to 27% of its baseline value compared with a 63%
      recovery in wild-type hearts (P<0.05). In FGF2 Tg hearts, an 88% recovery of
      postischemic function occurred (P<0.05). Myocardial infarct size was also reduced
      in FGF2 Tg hearts compared with wild-type hearts (13% versus 30%, P<0.05). There
      was a 2-fold increase in FGF2 release from Tg hearts compared with wild-type
      hearts (P<0.05). No significant alterations in coronary flow or capillary density
      were detected in any of the groups, implying that the protective effect of FGF2
      is not mediated by coronary perfusion changes. CONCLUSIONS: These results provide
      evidence that endogenous FGF2 plays a significant role in the cardioprotective
      effect against ischemia-reperfusion injury.

PMID- 14656921
TI  - Angiotensin-converting enzyme inhibition alters the fibrinolytic response to
      cardiopulmonary bypass.
AB  - BACKGROUND: Increased plasminogen activator inhibitor-1 (PAI-1) concentrations
      after coronary artery bypass grafting (CABG) are associated with increased risk
      of vein graft occlusion. Because angiotensin II stimulates PAI-1 expression, we
      tested the hypothesis that preoperative angiotensin-converting enzyme (ACE)
      inhibition decreases PAI-1 expression after CABG. METHODS AND RESULTS: We
      measured the effects of cardiopulmonary bypass (CPB) on PAI-1 antigen and tissue
      type plasminogen activator (tPA) antigen and activity in 31 patients taking an
      ACE inhibitor (ACEI) who were randomized to continue ACEI until the morning of
      surgery (ACEI group, n=19) or to discontinue it 48 hours before surgery (No-ACEI
      group, n=12). Arterial blood samples were taken at baseline before CPB, twice
      during CPB, after separation from CPB, and on postoperative day 1 (POD1). CPB
      caused an early decrease in PAI-1 antigen, followed by an increase in PAI-1
      antigen on POD1 (P<0.001 for effect of time). ACE inhibition attenuated the
      increase in PAI-1 antigen such that both PAI-1 antigen on POD1 (P=0.013) and the
      change in PAI-1 antigen from baseline to POD1 (P=0.009) were higher in the No
      ACEI group (from 17.0+/-5.0 to 48.7+/-8.8 ng/mL) versus the ACEI group (from
      19.9+/-3.4 to 33.1+/-6.2 ng/mL). There was no significant difference between the
      2 groups in intraoperative tPA activity (P=0.259); however, the increase in tPA
      activity was significantly greater in the ACEI group than in the No-ACEI group
      (P=0.030). CONCLUSIONS: Preoperative ACEI attenuates the increase in PAI-1 after
      CABG, suggesting a role for ACE inhibition in reducing the risk of acute graft
      thrombosis.

PMID- 14656922
TI  - Involvement of tissue factor pathway inhibitor in the coronary circulation of
      patients with acute coronary syndromes.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the endogenous inhibitor of
      the extrinsic coagulation pathway; however, its involvement during thrombus
      formation in patients with acute coronary syndromes (ACS) is still unknown.
      METHODS AND RESULTS: Transcardiac (aorta/coronary sinus) free and total TFPI
      (free + lipoprotein-bound form) levels, as well as TFPI/factor Xa (FXa) complex
      levels, were measured in plasma samples obtained from patients with acute
      myocardial infarction undergoing primary PTCA and patients with unstable angina
      undergoing urgent PTCA. Patients with stable angina undergoing elective PTCA
      served as controls. In addition, prothrombin fragment 1+2 and fibrinopeptide A
      plasma levels were measured. Samples were collected at baseline, after PTCA, and
      after stent deployment. In patients with ACS, both total and free TFPI plasma
      levels in the coronary sinus were significantly lower than the corresponding
      levels measured in the aorta at any time point of the study; conversely, a
      significant increase in TFPI/FXa complex plasma levels was observed in the
      coronary sinus as compared with the aorta. In contrast, in patients with stable
      angina, no differences were observed in TFPI and TFPI/FXa levels at baseline in
      the coronary sinus as compared with the aorta. CONCLUSIONS: TFPI is involved in
      the process of thrombus formation in vivo in patients with ACS, which suggests a
      potential role for TFPI in modulating coronary thrombosis.

PMID- 14656923
TI  - Transplantation of bone marrow-derived mononuclear cells in ischemic
      apolipoprotein E-knockout mice accelerates atherosclerosis without altering
      plaque composition.
AB  - BACKGROUND: Bone marrow-derived mononuclear cells (BM-MNCs) enhance postischemic
      neovascularization, and their therapeutic use is currently under clinical
      investigation. We evaluated the safety of BM-MNC-based therapy in the setting of
      atherosclerosis. METHODS AND RESULTS: Apolipoprotein E (apoE)-knockout (KO) mice
      were divided into 4 groups: 20 nonischemic mice receiving intravenous injection
      of either saline (n=10) or 10(6) BM-MNCs from wild-type animals (n=10) and 20
      mice with arterial femoral ligature receiving intravenous injection of either
      saline (n=10) or 10(6) BM-MNCs from wild-type animals (n=10) at the time of
      ischemia induction. Animals were monitored for 4 additional weeks.
      Atherosclerosis was evaluated in the aortic sinus. BM-MNC transplantation
      improved tissue neovascularization in ischemic hind limbs, as revealed by the
      210% increase in angiography score (P<0.0001), the 33% increase in capillary
      density (P=0.01), and the 65% increase in tissue Doppler perfusion score
      (P=0.0002). Hindlimb ischemia without BM-MNC transplantation or BM-MNC
      transplantation without ischemia did not affect atherosclerotic plaque size.
      However, transplantation of 10(6) BM-MNCs into apoE-KO mice with hindlimb
      ischemia induced a significant 48% to 72% increase in lesion size compared with
      the other 3 groups (P=0.0025), despite similar total cholesterol levels.
      Transplantation of 10(5) BM-MNCs produced similar results, whereas
      transplantation of 10(6) apoE-KO-derived BM-MNCs had neither proangiogenic nor
      proatherogenic effects. There was no difference in plaque composition between
      groups. CONCLUSIONS: BM-MNC therapy is unlikely to affect atherosclerotic plaque
      stability in the short term. However, it may promote further atherosclerotic
      plaque progression in an ischemic setting.

PMID- 14656924
TI  - Catecholamine-induced vascular wall growth is dependent on generation of reactive
      oxygen species.
AB  - Alpha1-adrenoceptor-dependent proliferation of vascular smooth muscle cells
      (VSMCs) is strongly augmented by vascular injury, and may contribute to intimal
      growth and lumen loss. Because reactive oxygen species (ROS) are increased by
      injury and have been implicated as second messengers in proliferation of VSMCs,
      we investigated the role of ROS in catecholamine-induced VSMC growth. Rat aortae
      were isolated 4 days after balloon injury, maintained in organ culture under
      circumferential wall tension, and exposed to agents for 48 hours. The
      antioxidants N-acetylcysteine (NAC, 10 mmol/L) and Tiron (5 mmol/L) and the
      flavin-inhibitor diphenylene iodonium (DPI, 20 micromol/L) abolished
      norepinephrine-induced increases in protein synthesis and DNA content in media.
      In aortic sections, norepinephrine augmented ROS production (dihydroethidium
      confocal microscopy), which was dose-dependently inhibited by NAC, Tiron, and
      DPI. In cultured VSMCs, phenylephrine caused time- and dose-dependent ROS
      generation (aconitase activity), had similar efficacy to thrombin (1 U/mL), and
      was eliminated by the superoxide dismutase (SOD) mimetic Mn-(III)-tetrakis-(4
      benzoic-acid)-porphyrin-chloride (200 micromol/L) and Tiron. Phenylephrine
      induced ROS production and increases in DNA and protein content were blocked by
      prazosin (0.3 micromol/L) and abolished in p47phox-/- cells. PEG-SOD (25 U/mL)
      had little effect, whereas PEG-catalase (50 U/mL) eliminated phenylephrine
      induced proliferation in VSMCs. DPI (10 micromol/L) and apocynin (30 micromol/L)
      abolished phenylephrine-stimulated mitogenesis, whereas inhibitors of other
      intracellular ROS sources had not effect. Furthermore, PE increased p47phox
      expression (RT-PCR). These data demonstrate that the trophic effect of
      catecholamines on vascular wall cells is dependent on a ROS-sensitive step that
      we hypothesize consists of activation of the NAD(P)H-dependent vascular oxidase.

PMID- 14656925
TI  - Agonist-induced activation of matrix metalloproteinase-7 promotes
      vasoconstriction through the epidermal growth factor-receptor pathway.
AB  - Matrix metalloproteinase (MMP)-dependent shedding of heparin-binding epidermal
      growth factor (HB-EGF) and subsequent activation of the EGF receptor (EGFR) in
      the cardiovasculature is emerging as a unique mechanism signaling growth effects
      of diverse G protein-coupled receptors (GPCRs). Among these GPCRs are
      adrenoceptors and angiotensin receptors that contribute to the pathogenesis of
      hypertension through their vasoconstrictive and growth effects. Focusing on
      alpha(1b)-adrenoceptors, we suggest here that MMP-dependent activation of the
      EGFR promotes vasoconstriction as well as growth. We identified MMP-7 as a major
      HB-EGF sheddase in rat mesenteric arteries and alpha(1b)-adrenoceptors,
      angiotensin receptors, and hypertension-stimulated MMP-7 activity. Adrenoceptors
      stimulated EGFR autophosphorylation in arteries, and this transactivation was
      opposed by the MMP-7 inhibitor GM6001 as well as MMP-7-specific antibodies. In
      isolated microperfused arteries, blockade of EGFR transactivation with inhibitors
      of the EGFR (AG1478 and PD153035), HB-EGF (CRM197 and neutralizing antibodies),
      or MMPs (doxycycline) inhibited adrenergic vasoconstriction. In spontaneously
      hypertensive rats but not in normotensive rats, the inhibition of MMPs with
      doxycycline (19.2 mg/d from week 7 until week 12) reduced systolic blood pressure
      and attenuated HB-EGF shedding in the mesenteric arteries. These findings suggest
      a previously unknown mechanism of vasoregulation whereby agonists of certain
      GPCRs (such as adrenoceptors and angiotensin receptors) activate MMPs (such as
      MMP-7) that shed EGFR ligands (such as HB-EGF), which then activate the EGFR,
      thereby promoting vasoconstriction as well as growth. Because this mechanism is
      triggered by agonists typically overexpressed in hypertension, its blockade may
      have therapeutic potential for simultaneously inhibiting pathological
      vasoconstriction and growth in hypertensive disorders.

PMID- 14656926
TI  - Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme
      oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro,
      in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery.
AB  - The recently described hemoglobin scavenger receptor CD163 mediates the
      endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb
      induced oxidative tissue damage after hemolysis. Although CD163 has been
      indirectly associated with antiinflammatory and atheroprotective activity, no
      ligand-receptor-effector pathway has yet been described for this receptor. To
      understand the significance of CD163 and more clearly define downstream pathways
      linked to inflammatory resolution, we studied the expression and function of
      CD163 in human monocytes/macrophages using both in vitro and in vivo models.
      Differentiation of human blood monocytes into macrophages either by in vitro
      culture or in resolving cantharidin-induced skin blisters led to an equivalent
      increase (>15x) in CD163 expression. Elevated CD163 levels were also noted on
      circulating monocytes in cardiac surgical patients during the resolution phase of
      the systemic inflammatory response to cardiopulmonary bypass surgery. In each
      case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10
      secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of
      interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an
      autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24
      to 48 hours after the onset of cardiopulmonary bypass surgery. These results
      identify novel antiinflammatory and cytoprotective effector pathways in human
      monocytes/macrophages related to Hb scavenging and metabolism, which may have
      relevance in atheroprotection, wound healing, and patient recovery
      postoperatively.

PMID- 14656927
TI  - Calcineurin/NFAT coupling participates in pathological, but not physiological,
      cardiac hypertrophy.
AB  - Calcineurin (PP2B) is a calcium/calmodulin-activated, serine-threonine
      phosphatase that transmits signals to the nucleus through the dephosphorylation
      and translocation of nuclear factor of activated T cell (NFAT) transcription
      factors. Whereas calcineurin-NFAT signaling has been implicated in regulating the
      hypertrophic growth of the myocardium, considerable controversy persists as to
      its role in maintaining versus initiating hypertrophy, its role in pathological
      versus physiological hypertrophy, and its role in heart failure. To address these
      issues, NFAT-luciferase reporter transgenic mice were generated and
      characterized. These mice showed robust and calcineurin-specific activation in
      the heart that was inhibited with cyclosporin A. In the adult heart, NFAT
      luciferase activity was upregulated in a delayed, but sustained manner throughout
      eight weeks of pathological cardiac hypertrophy induced by pressure-overload, or
      more dramatically following myocardial infarction-induced heart failure. In
      contrast, physiological hypertrophy as produced in two separate models of
      exercise training failed to show significant calcineurin-NFAT coupling in the
      heart at multiple time points, despite measurable increases in heart to body
      weight ratios. Moreover, stimulation of hypertrophy with growth hormone-insulin
      like growth factor-1 (GH-IGF-1) failed to activate calcineurin-NFAT signaling in
      the heart or in culture, despite hypertrophy, activation of Akt, and activation
      of p70 S6K. Calcineurin Abeta gene-targeted mice also showed a normal
      hypertrophic response after GH-IGF-1 infusion. Lastly, exercise- or GH-IGF-1
      induced cardiac growth failed to show induction of hypertrophic marker gene
      expression compared with pressure-overloaded animals. Although a direct cause-and
      effect relationship between NFAT-luciferase activity and pathological hypertrophy
      was not proven here, our results support the hypothesis that separable signaling
      pathways regulate pathological versus physiological hypertrophic growth of the
      myocardium, with calcineurin-NFAT potentially serving a regulatory role that is
      more specialized for maladaptive hypertrophy and heart failure.

PMID- 14656928
TI  - Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart:
      involvement of reactive oxygen species and cardiolipin.
AB  - Reactive oxygen species (ROS) are considered an important factor in
      ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration is an
      important source of ROS production and hence a potential contributor to cardiac
      reperfusion injury. In this study, we have examined the effect of ischemia and
      ischemia followed by reperfusion of rat hearts on various parameters related to
      mitochondrial function, such as complex I activity, oxygen consumption, ROS
      production, and cardiolipin content. The activity of complex I was reduced by 25%
      and 48% in mitochondria isolated from ischemic and reperfused rat heart,
      respectively, compared with the controls. These changes in complex I activity
      were associated with parallel changes in state 3 respiration. The capacity of
      mitochondria to produce H2O2 increased on reperfusion. The mitochondrial content
      of cardiolipin, which is required for optimal activity of complex I, decreased by
      28% and 50% as function of ischemia and reperfusion, respectively. The lower
      complex I activity in mitochondria from reperfused rat heart could be completely
      restored to the level of normal heart by exogenous added cardiolipin. This effect
      of cardiolipin could not be replaced by other phospholipids nor by peroxidized
      cardiolipin. It is proposed that the defect in complex I activity in
      ischemic/reperfused rat heart could be ascribed to a ROS-induced cardiolipin
      damage. These findings may provide an explanation for some of the factors
      responsible for myocardial reperfusion injury.

PMID- 14656929
TI  - Perlecan-induced suppression of smooth muscle cell proliferation is mediated
      through increased activity of the tumor suppressor PTEN.
AB  - We were interested in the elucidation of the interaction between the heparan
      sulfate proteoglycan, perlecan, and PTEN in the regulation of vascular smooth
      muscle cell (SMC) growth. We verified serum-stimulated DNA synthesis, and Akt and
      FAK phosphorylation were significantly reduced in SMCs overexpressing wild-type
      PTEN. Our previous studies showed perlecan is a potent inhibitor of serum
      stimulated SMC growth. We report in the present study, compared with SMCs plated
      on fibronectin, serum-stimulated SMCs plated on perlecan exhibited increased PTEN
      activity, decreased FAK and Akt activities, and high levels of p27, consistent
      with SMC growth arrest. Adenoviral-mediated overexpression of constitutively
      active Akt reversed perlecan-induced SMC growth arrest while morpholino antisense
      mediated loss of endogenous PTEN resulted in increased growth and phosphorylation
      of FAK and Akt of SMCs on perlecan. Immunohistochemical and Western analyses of
      balloon-injured rat carotid artery tissues showed a transient increase in
      phosphoPTEN (inactive) after injury, correlating to high rates of neointimal cell
      replication; phosphoPTEN was largely limited to actively replicating SMCs.
      Similarly, in the developing rat aorta, we found increased PTEN activity
      associated with increased perlecan deposition and decreased SMC replication
      rates. However, significantly decreased PTEN activity was detected in aortas of
      perlecan-deficient mouse embryos, consistent with SMC hyperplasia observed in
      these animals, compared with E17.5 heterozygous controls that produce abundant
      amounts of perlecan at this developmental time point. Our data show PTEN is a
      potent endogenously produced inhibitor of SMC growth and increased PTEN activity
      mediates perlecan-induced suppression of SMC proliferation.

PMID- 14656930
TI  - Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells.
AB  - Cardiomyocyte regeneration is limited in adult life. Thus, the identification of
      a putative source of cardiomyocyte progenitors is of great interest to provide a
      usable model in vitro and new perspective in regenerative therapy. As adipose
      tissues were recently demonstrated to contain pluripotent stem cells, the
      emergence of cardiomyocyte phenotype from adipose-derived cells was investigated.
      We demonstrated that rare beating cells with cardiomyocyte features could be
      identified after culture of adipose stroma cells without addition of 5
      azacytidine. The cardiomyocyte phenotype was first identified by morphological
      observation, confirmed with expression of specific cardiac markers,
      immunocytochemistry staining, and ultrastructural analysis, revealing the
      presence of ventricle- and atrial-like cells. Electrophysiological studies
      performed on early culture revealed a pacemaker activity of the cells. Finally,
      functional studies showed that adrenergic agonist stimulated the beating rate
      whereas cholinergic agonist decreased it. Taken together, this study demonstrated
      that functional cardiomyocyte-like cells could be directly obtained from adipose
      tissue. According to the large amount of this tissue in adult mammal, it could
      represent a useful source of cardiomyocyte progenitors.

PMID- 14656931
TI  - Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice.
AB  - Increasing evidence supports the involvement of inflammation in the early phases
      of atherogenesis. Recruitment of leukocytes within the vascular wall, controlled
      by chemokines, is an essential process in the development of this common disease.
      In this study, we report that blocking a chemokine pathway in vivo with the CC
      chemokine antagonist Met-RANTES reduces the progression of atherosclerosis in a
      hypercholesterolemic mouse model. The reduction of lesions was correlated with a
      diminution of expression of several major chemokines and chemokine receptors, a
      decrease in leukocyte infiltration, and an increase of collagen-rich atheroma,
      features associated with stable atheroma. Treatment was well tolerated and serum
      lipid profiles were not affected. Whereas genetically engineered mice with
      deletion of either a CC chemokine or its receptor have demonstrated resistance to
      disease, to our knowledge, this is the first demonstration that treatment with a
      chemokine receptor antagonist limits the progression of atherosclerosis in vivo.
      Thus, our findings indicate that blockade of chemokine receptor/ligand
      interactions might become a novel therapeutic strategy to reduce the evolution of
      this common disease.

PMID- 14656932
TI  - Mechanistic role of cytochrome P450 monooxygenases in oxidized low-density
      lipoprotein-induced vascular injury: therapy through LOX-1 receptor antagonism?
AB  - Oxidized low-density lipoprotein (oxLDL) is an important risk factor for vascular
      injury. Its role on coronary vasoconstriction remains speculative. Endothelial
      monooxygenases (cytochrome P450s [CYPs]) are regulators of vascular tonus through
      production of epoxy fatty acids. We investigated the effects of oxLDL on CYP
      monooxygenases in human arterial coronary endothelial cells and explanted healthy
      and atherosclerotic aortae. We found oxLDL to induce radical oxygen species
      production via the action of NADPH oxidase NOX4. Intracellular radical oxygen
      species production prompted reduced protein expression of the transcriptional
      regulator nuclear factor 1 (NF-1). We identified novel DNA binding sites for NF-1
      in promoter regions of CYPs. DNA binding of NF-1 was confirmed by electromobility
      shift assays. OxLDL repressed DNA binding of NF-1 and diminished transcript level
      of CYP genes targeted by this factor. The production of endothelial-derived
      hyperpolarization factor, a key regulator of vascular tonus, was also reduced.
      Repression of CYP monooxygenases was reversed, and production of endothelial
      derived hyperpolarization factor was normalized after treatment of endothelium
      with the lectin-like oxLDL receptor antagonist kappa-carrageenan or blocking of
      LOX-1 with a specific antibody. This suggests a mechanistic role of CYP
      monooxygenases in oxLDL-induced vascular injury. Therapy of endothelial
      dysfunction through LOX-1 receptor antagonism will be an interesting avenue to
      explore. The full text of this article is available online at
      http://www.circresaha.org.

PMID- 14656933
TI  - Cdc42 regulates the restoration of endothelial barrier function.
AB  - The mechanisms involved in the restoration of endothelial cell junctions
      subsequent to barrier disruption remain unclear. It is known that formation of
      adherens junctions (AJs) affects cytoskeletal actin arrangement and that Rho
      GTPases regulate the state of actin polymerization. In the present study, we
      examined the role of the Rho GTPases, Rho, Rac, and Cdc42 in the reannealing of
      AJs. We studied the response to thrombin, which increases endothelial
      permeability through disassembly of AJs, followed by recovery of barrier function
      through junctional reannealing within 2 hours. Cdc42 was activated late, at
      approximately 1 hour after thrombin exposure, concurrent with its translocation
      from the cytoplasm to the membrane. Activation and translocation of Cdc42
      preceded the reformation of AJs. Expression of the dnCdc42 mutant (N17Cdc42)
      significantly delayed the reformation of the VE-cadherin-containing AJs and
      restoration of endothelial barrier function. We also studied the lung
      microcirculation to address the in vivo relevance of Cdc42 signaling in barrier
      restoration. N17Cdc42 expression in the mouse lung endothelium markedly
      attenuated the endothelial barrier recovery after the permeability increase
      induced by activation of the thrombin receptor protease-activated receptor-1.
      These findings demonstrate the critical function of Cdc42 in restoring AJ
      dependent, endothelial cell homotypic adhesion and barrier function. The delayed
      activation of Cdc42 represents a negative-feedback mechanism that signals AJ
      reassembly after the increase in endothelial permeability induced by inflammatory
      mediators such as thrombin.

PMID- 14656934
TI  - Bone marrow-derived cells do not incorporate into the adult growing vasculature.
AB  - Bone marrow-Derived cells have been proposed to form new vessels or at least
      incorporate into growing vessels in adult organisms under certain physiological
      and pathological conditions. We investigated whether bone marrow-Derived cells
      incorporate into vessels using mouse models of hindlimb ischemia (arteriogenesis
      and angiogenesis) and tumor growth. C57BL/6 wild-type mice were lethally
      irradiated and transplanted with bone marrow cells from littermates expressing
      enhanced green fluorescent protein (GFP). At least 6 weeks after bone marrow
      transplantation, the animals underwent unilateral femoral artery occlusions with
      or without pretreatment with vascular endothelial growth factor or were
      subcutaneously implanted with methylcholanthrene-induced fibrosarcoma (BFS-1)
      cells. Seven and 21 days after surgery, proximal hindlimb muscles with growing
      collateral arteries and ischemic gastrocnemius muscles as well as grown tumors
      and various organs were excised for histological analysis. We failed to
      colocalize GFP signals with endothelial or smooth muscle cell markers.
      Occasionally, the use of high-power laser scanning confocal microscopy uncovered
      false-positive results because of overlap of different fluorescent signals from
      adjacent cells. Nevertheless, we observed accumulations of GFP-positive cells
      around growing collateral arteries (3-fold increase versus nonoccluded side,
      P<0.001) and in ischemic distal hindlimbs. These cells were identified as
      fibroblasts, pericytes, and primarily leukocytes that stained positive for
      several growth factors and chemokines. Our findings suggest that in the adult
      organism, bone marrow-Derived cells do not promote vascular growth by
      incorporating into vessel walls but may function as supporting cells.

PMID- 14656936
TI  - Ethical aspects of molecular epidemiology of cancer.
AB  - In molecular epidemiology of cancer where many studies are genetic in nature and
      they are done among healthy people, ethical issues require special consideration.
      Genetic information differs from other health care information in that it is
      predictive in nature, and it always involves at least family members, but in some
      genetically very homogeneous populations even a wider group. General discussion
      of the potential good and harm should be encouraged more, so that it would be
      possible for lay people to make informed decisions. Personal involvement of
      scientists in education of public, general discussion and considering their own
      studies from the point of view of the study subject and their family is in the
      end the only way to ensure that the spirit of international regulations of ethics
      are realized in practise.

PMID- 14656938
TI  - Cellular protein kinase C isozyme regulation by exogenously delivered
      physiological disulfides--implications of oxidative protein kinase C regulation
      to cancer prevention.
AB  - We reported previously that cystine produces regulatory responses in purified,
      recombinant human protein kinase C-delta (PKCdelta) and PKCepsilon via S
      thiolation-triggered mechanisms that are consistent with a cancer preventive
      effect, i.e. stimulation of the pro-apoptotic, tumor-suppressive isozyme PKCdelta
      and inactivation of the growth-stimulatory, oncogenic isozyme PKCepsilon, at S
      cysteinylation stoichiometries that correspond to modification of a single redox
      regulatory cysteine (Cys) switch in each isozyme. In this report, we show that
      the oxidative regulatory responses of purified PKCdelta and PKCepsilon to cystine
      are recapitulated in disulfide-treated cells. We report that treatment of COS7
      PKCepsilon transfectants with the cystine precursor cystine dimethyl ester (CDME)
      produced concentration- and time-dependent PKCepsilon inactivation that was
      associated with oxidative PKCepsilon modification manifested as attenuated band
      intensity in PKCepsilon immunoblot analyses, and that both PKCepsilon
      inactivation and modification were reversed by dithiothreitol (DTT) as well as by
      thioredoxin. We also show that CDME induced biphasic PKCdelta regulation in COS7
      PKCdelta transfectants, with DTT-irreversible PKCdelta stimulation at low and DTT
      reversible PKCdelta inactivation at high CDME concentrations. The degrees of
      PKCdelta versus PKCepsilon inactivation by CDME treatment of COS7-PKC
      transfectants indicate substantial resistance of PKCdelta to inactivation. The
      PKCdelta stimulatory response in COS7-PKCdelta cells was triggered only by the
      disulfide agent and not by its reduced thiol counterpart, providing evidence for
      an oxidative mechanism. Also paralleling the oxidative stimulation of purified
      PKCdelta by cystine, the stimulation of PKCdelta elicited by CDME treatment of
      cells involved a stable structural change, which was evident from the stability
      of the stimulated form of PKCdelta to immunoprecipitation. Demonstration of
      oxidative regulation of cellular PKCdelta and PKCepsilon by disulfides in this
      report provides evidence that redox-regulatory sites in PKCdelta and PKCepsilon
      may offer novel targets for development of cancer preventive or therapeutic
      agents that selectively inactivate PKCepsilon or stimulate PKCdelta.

PMID- 14656937
TI  - Implications for oxidative and nitrative stress in the pathogenesis of AIDS
      related Kaposi's sarcoma.
AB  - AIDS-related Kaposi's sarcoma (AIDS-KS), which is the most prevalent AIDS related
      cancer, arises in a unique environment characterized by profound
      immunosuppression in conjunction with sustained immunostimulation. Persistent
      inflammation and the accompanying increased production of reactive species can
      promote carcinogenesis by numerous routes including sustained cell proliferation,
      initiation of nuclear and mitochondrial DNA mutations and induction of a
      proangiogenic environment. Furthermore, during conditions of continuous
      inflammation, protein nitration can result in irreversible inactivation of
      enzymes including the cytoprotective and reactive species degrading enzyme,
      mitochondrial superoxide dismutase (MnSOD). Because MnSOD serves as a putative
      tumor suppressor gene in addition to its reactive species inactivating
      capacities, the loss of MnSOD's cytoprotective functions could markedly
      facilitate malignant transformation. The purpose of this study was to investigate
      biochemical and molecular pathways by which reactive species facilitate AIDS-KS
      pathogenesis. Immunohistochemical studies of AIDS-KS tumors showed intense AIDS
      KS lesional cell staining for MnSOD, inducible nitric oxide synthase (NOS 2) and
      the presence of a cellular 'fingerprint' of nitrative stress, 3-nitrotyrosine.
      Collectively, these results that imply reactive species stress occurs in situ.
      Similarly, cultured AIDS-KS cells derived from the AIDS-KS tumors contained both
      MnSOD protein and the 'high output' isoform, NOS 2. Co-localization studies
      established that the mitochondria are a primary site for 3-nitrotyrosine
      localization and immunoprecipitation/immunoblotting experiments confirmed that
      MnSOD tyrosine nitration occurs in AIDS-KS cells. Functional SOD assays showed
      that AIDS-KS cells possess significantly lower MnSOD activity relative to matched
      control cells; findings which correspond with ongoing MnSOD tyrosine nitration
      and subsequent inactivation within AIDS-KS cells. These results, which show in
      situ evidence of reactive species stress within AIDS-KS tumors and functional
      deficits attributable to nitrative stress in tumor-derived AIDS-KS lesional
      cells, imply that reactive species are intimately associated with AIDS-KS
      pathogenesis and provide insights for development of novel strategies for AIDS-KS
      clinical treatments.

PMID- 14656939
TI  - Mammary carcinogenesis and molecular analysis of in vivo cII gene mutations in
      the mammary tissue of female transgenic rats treated with the environmental
      pollutant 6-nitrochrysene.
AB  - We determined the mutant fractions (MF) and mutational specificities in the cII
      gene in histologically confirmed normal, non-involved and tumor mammary tissues
      of female transgenic (Big Blue F344 x Sprague-Dawley)F1 rats treated with the
      environmental pollutant 6-nitrochrysene (6-NC). At 30 days of age, three groups
      were set up for oral treatment with 6-NC dissolved in trioctanoin, or trioctanoin
      alone once a week for 8 weeks. Two dose levels of 6-NC (100 and 200 micromol/rat)
      were selected on the basis of our previous carcinogenicity bioassays with CD
      rats. The rats were decapitated 32 weeks after the last carcinogen dose. Both
      incidence and multiplicity of mammary adenocarcinomas were significantly elevated
      in the high dose (36%, 0.57, P < 0.01) group but at the low dose these outcomes
      (16%, 0.23, P < 0.1) were not significantly different from those of control rats
      (3%, 0.03). The MF in normal, non-involved and tumor tissues from the mammary
      glands of 6-NC-treated rats were comparable. At the high and low doses,
      respectively (4.8 +/- 2.0, 3.2 +/- 2.1) the MF of 6-NC-treated rats, were
      significantly higher (P < 0.05) than that observed in control rats (1.2 +/- 0.6).
      Control mutants consisted primarily of GC --> AT transitions, whereas 6-NC
      induced mutants were comprised of several major classes of mutations with GC -->
      TA, GC --> CG, AT --> GC and AT --> TA as the most prevalent. Further studies
      indicated that the structures of 6-NC-DNA adducts in the mammary tissue are
      consistent with the mutational specificities. This is the first report that
      defines the relationship between carcinogenesis and mutagenesis, as well as
      between structures of 6-NC-DNA adducts and mutation characteristics in the target
      organ in vivo.

PMID- 14656940
TI  - Cytochrome P450 1B1 and catechol-O-methyltransferase polymorphisms and
      endometrial cancer susceptibility.
AB  - Estrogen production and metabolism play critical roles in the development and
      pathogenesis of endometrial carcinoma. Cytochrome P450 1B1 (CYP1B1) and catechol
      O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway
      that result in the hydroxylation and conjugation of estradiol, respectively. We
      evaluated the association between the CYP1B1 Leu432Val and CYP1B1 Asn453Ser
      polymorphisms and the COMT Val158Met polymorphism and invasive endometrial cancer
      risk in a case-control study nested within the Nurses' Health Study (n = 222
      cases, 666 controls). We also evaluated whether body mass index (BMI),
      postmenopausal hormone (PMH) use and cigarette smoking modified the associations
      of the CYP1B1 and COMT genotypes and endometrial cancer risk. Conditional
      logistic regression was used to calculate the adjusted odds ratios (OR) and 95%
      confidence intervals (CI) to quantify the risk of endometrial cancer among
      subjects who had at least one variant allele compared with subjects who were
      homozygous for the wild-type allele. Carriers of the CYP1B1 Ser allele had a
      statistically significant decreased risk of endometrial cancer (OR = 0.62; 95%
      CI, 0.42-0.91); there was no significant association between the CYP1B1 Val
      allele and endometrial cancer risk (OR = 1.10; 95% CI, 0.75-1.59). Compared with
      the COMT Val/Val wildtype genotype, the adjusted OR of endometrial cancer for
      women with the COMT Val/Met or COMT Met/Met genotype was 0.96 (95% CI, 0.65
      1.43). We did not observe any effect modification by BMI, PMH use and cigarette
      smoking for the CYP1B1 and COMT genotypes. Our data suggest, that the CYP1B1 Ser
      allele may decrease endometrial cancer risk by altering the production of
      catechol estrogens. However, further studies are warranted to elucidate the role
      of CYP1B1 in endometrial cancer.

PMID- 14656941
TI  - Carcinogen exposure differentially modulates RAR-beta promoter hypermethylation,
      an early and frequent event in mouse lung carcinogenesis.
AB  - The retinoic acid receptor beta (RAR-beta) gene encodes one of the primary
      receptors for retinoic acid, an important signaling molecule in lung growth,
      differentiation and carcinogenesis. RAR-beta has been shown to be down-regulated
      by methylation in human lung cancer. We have used previously lung tumors induced
      in mice to evaluate the timing and effect of specific carcinogen exposures on
      targeting genes altered in human lung cancer. These studies were extended to
      characterize the role of methylation of the RAR-beta gene in murine lung cancers.
      After treatment with the demethylating agent 5-aza-2'-deoxycytidine (DAC), RAR
      beta was re-expressed in silenced cell lines or expressed at a higher rate than
      without DAC, supporting methylation as the inactivating mechanism. Bisulfite
      sequencing detected dense methylation in the area of the CpG island that
      contained the 5' untranslated region and the first translated exon in non
      expressing cell lines, compared with minimal and heterogeneous methylation in
      normal mouse lung. Methylation-specific PCR revealed that this gene is targeted
      differentially by carcinogen exposures with the detection of methylated alleles
      in virtually all primary tumors associated with cigarette smoke or 4
      methylnitrosamino-1-(3-pyridyl)-butanone (NNK) in contrast to half of tumors
      induced by methylene chloride or vinyl carbamate. RAR-beta methylation was also
      detected in 54% of preneoplastic hyperplasias induced by treatment with NNK.
      Bisulfite sequencing of both premalignant and malignant lesions detected dense
      methylation in the same area observed in cell lines, substantiating that this
      gene is functionally inactivated at the earliest histologic stage of
      adenocarcinoma development. These studies demonstrate that aberrant methylation
      of RAR-beta is an early and common alteration in murine lung tumors induced by
      several environmentally relevant exposures.

PMID- 14656942
TI  - Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model
      recapitulating the multi-stage progression of human cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a lethal disease, afflicting many thousands the world
      over. Human CCA develops through a multi-step progression model, preceded by the
      onset of dysplasia in the cholangiolar ductal epithelium. An animal model of
      multi-step carcinogenesis in the biliary tree will enable the study of genetic
      changes in human CCA, and provide an avenue for chemoprevention strategies. We
      describe an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates
      the histologic progression of human CCA. Male Sprague-Dawley (SD) rats (n = 170),
      weighing 350 +/- 20 g, were used in this study. Drinking water with TAA 300 mg/l
      was administered orally, and the liver was harvested and examined histologically
      at weekly intervals, beginning at 5 weeks after initiation of TAA. Harvested
      tissues were formalin-fixed and paraffin embedded for morphologic and
      immunohistochemical studies. Multifocal bile ductular proliferation with
      intestinal metaplasia (presence of goblet cells) and increasing histologic atypia
      (biliary dysplasia) was observed by the 9th week of TAA administration. Biliary
      cytokeratin (CK19)-expressing invasive intestinal-type CCA with stromal
      desmoplasia was evident at the 16th week, and by the 22nd week, the yield rate
      for CCAs had increased to 100%. Invasive CCAs preceded the development of hepatic
      cirrhosis by at least 4 weeks; the earliest incidence of hepatic fibrosis was
      observed beginning at 20 weeks post-TAA administration. The progression from
      normal cholangioles to biliary dysplasia to invasive CCA was accompanied by up
      regulation of the proto-oncogenes c-met and c-erbB-2, tyrosine kinase receptors
      over-expressed in human CCAs. The study was terminated at 6 months, at which time
      no systemic metastases or deaths were observed. Oral administration of TAA in
      drinking water to male SD rats provides a reproducible animal model for
      development of CCA with a high yield rate. In particular, the presence of biliary
      dysplasia beginning at the 9th week, which progresses to invasive CCA, mimics the
      multi-step model of human CCA. The TAA rat model may serve as a powerful pre
      clinical platform for therapeutic and chemoprevention strategies for human CCA.

PMID- 14656943
TI  - Effective asymmetry in gap junctional intercellular communication between
      populations of human normal lung fibroblasts and lung carcinoma cells.
AB  - The dysfunction of homologous and/or heterologous gap junctional intercellular
      communication (GJIC) has been implicated in tumorigenesis of many kinds of cells.
      Here we have characterized GJIC and the expression of connexins in six human lung
      carcinoma cell lines and normal lung fibroblasts (HLF). Compared with HLF, all
      the carcinoma cells showed reduced or little homologous GJIC. They expressed
      remarkably reduced connexin(Cx)43 mRNA and variable levels of Cx45 mRNA, but
      neither Cx43 nor Cx45 protein could be detected. However, using a preloading
      assay, transfer of calcein was observed between donor HLF cells and first order
      neighboring recipient tumor cells (recipient cells in 1000-fold excess). Transfer
      from tumor to HLF cells under the same conditions was not seen, although
      increasing the ratio of donor tumor cells to recipient HLF cells and plating the
      cells at low density did reveal weak transfer from tumor cells to HLF.
      Transfection of Cx43 into giant cell carcinoma PG cells increased homologous
      communication and eliminated the rectifying behavior of heterologous
      communication. This indicates that the apparent rectification of dye transfer
      between normal and tumor cells was a product of low rates of heterologous
      transfer linked to (i) rapid dilution of the dye to below detectable limits
      through a very well coupled cell population (tumor to HLF) and (ii) concentration
      of dye in immediate neighbors in a poorly coupled cell population (HLF to tumor
      cells). These results suggest that the coupling levels may need to exceed a
      certain threshold to allow propagation of signals over a sufficient distance to
      affect behavior of a cell population. We propose that the relative rates of
      heterologous and homologous coupling of cell populations and the 'pool size' of
      shared metabolites in tumor cells and the surrounding normal tissue are likely to
      be very important in the regulation of their growth.

PMID- 14656944
TI  - Microsatellite instability mutator phenotype in hepatocellular carcinoma in non
      alcoholic and non-virally infected normal livers.
AB  - Microsatellite instability (MSI) seems to be a rare event in hepatocarcinogenesis
      and might actually be associated with the progression of hepatocellular carcinoma
      (HCC) in which the liver is often the site of chronic hepatitis or cirrhosis. The
      aim of this work was to define the MSI phenotype in HCC affecting exclusively
      normal livers to avoid slippage errors due to cirrhosis. One hundred and sixty
      four patients with HCC affecting non-cirrhotic livers were operated on in our
      hospital between 1984 and 2001. We analyzed 37 patients selected for low alcohol
      consumption and the absence of HBV or HCV infection. All the livers were
      histologically normal. MSI was analyzed according to the criteria defined during
      the conference consensus workshop for colorectal cancer. High MSI (MSI-H > 30%)
      was found in 6 (16%) and low MSI (MSI-L < 30%) in 10 (27%) of the 37 HCCs. None
      of the 10 microsatellite markers tested were altered in the remaining 21 tumors
      (57%). Immunohistochemistry showed that normal amounts of hMLH1 and hMSH2 were
      present both in MSI-H and in MSI-L HCCs. MSI-H was significantly associated with
      more aggressive histological tumor features and a shorter median delay before
      recurrence. Thus, we have found a small subgroup of HCC tumors which can be
      considered as a new clinical/histological entity.

PMID- 14656945
TI  - The effects of diet on DNA bulky adduct levels are strongly modified by GSTM1
      genotype: a study on 634 subjects.
AB  - Frequent consumption of fresh fruit and vegetables, and polymorphisms in the
      detoxifying enzyme glutathione S-transferase M1 (GSTM1) and other metabolic genes
      have been shown to modulate cancer risk at some sites. We have shown recently
      that DNA adducts, a reliable indicator of genotoxic damage and, possibly, of
      cancer risk, are modulated by plasma levels of selected micronutrients. Here we
      further investigate the association between DNA adduct levels and consumption of
      major food groups and foods, and the estimated dietary intake of nutrients,
      taking into account the possible modifying effect of metabolic polymorphisms, in
      a larger sample of 634 healthy adults enrolled in a prospective study in Italy.
      DNA adducts and five polymorphic metabolic genotypes (GSTM1, GSTT1, NAT2, CYP1A1
      and MTHFR) were determined in peripheral leukocytes by using 32P-postlabeling
      technique and PCR methods. DNA bulky adducts (mean: 7.82 +/- 0.40/10(9) nt) were
      detected in 482/634 samples (76.0%). Overall, DNA adduct levels were
      significantly and inversely associated with the intake of raw leafy vegetables (P
      = 0.02), non-citrus fruits (P = 0.04), potassium (P = 0.01) and beta-carotene (P
      = 0.05). No association was evident with the five genotypes. Stratification by
      GSTM1 genotype showed strong inverse associations of DNA adduct levels with
      increasing consumption of all vegetables combined (P = 0.04), leafy vegetables (P
      = 0.004), raw leafy vegetables (P = 0.002) and fish (P = 0.03) among 307 GSTM1
      null subjects; strong inverse associations also emerged with estimated dietary
      intakes of beta-carotene (P = 0.004), vitamin E (P = 0.004), niacin (P = 0.02)
      and potassium (P = 0.01). In contrast, no association emerged among 295 subjects
      with a GSTM1-wild genotype. Overall, statistically significant interactions in
      predicting DNA adduct levels were observed between the GSTM1-null genotype and
      consumption of leafy vegetables (P = 0.01), white meat (P = 0.04), and intake of
      vitamin C (P = 0.04), vitamin E (P = 0.05) and beta-carotene (P = 0.02). Our
      results suggest that the role of a diet rich in antioxidants in preventing or
      reducing DNA adduct formation is restricted to subjects lacking the detoxifying
      activity of GSTM1 isoenzyme (approximately 50% of the general population).

PMID- 14656946
TI  - The bile acid deoxycholic acid (DCA) at neutral pH activates NF-kappaB and
      induces IL-8 expression in oesophageal cells in vitro.
AB  - Barrett's oesophagus patients accumulate chromosomal defects during the
      histological progression to cancer, one of the most prominent of which is the
      amplification of the whole of chromosome 4. We aimed to study the role that the
      transcription factor NF-kappaB, a candidate cancer- promoting gene, present on
      chromosome 4, plays in Barrett's oesophagus, using OE33 cells as a model.
      Specifically, we wanted to determine if NF-kappaB was activated by exposure to
      bile acid (deoxycholic acid) in oesophageal cells. We employed pathway specific
      cDNA microarrays and real-time PCR, to first identify bile acid induced genes and
      specifically to investigate the role of NF-kappaB. An NF-kappaB reporter system
      was used, as well as an inhibitor of NF-kappaB (pyrrolidine dithiocarbamate) to
      confirm the activation of NF-kappaB by bile. We show that physiological levels of
      DCA (100-300 microM) were capable of activating NF-kappaB in OE33 cells and
      inducing NF-kappaB target gene expression (particularly IkappaB and IL-8). Other
      gene expression abnormalities were also shown to be induced by DCA. Importantly,
      preliminary experiments showed that NF-kappaB activation by bile occurred at
      neutral pH, but not at acid pH. Acidic bile did however cause over-expression of
      the c-myc oncogene, as reported previously. Hence, we present data showing that
      NF-kappaB may be a key mediator of carcinogenesis in bile exposed Barrett's
      tissues. In addition, neutral bile acids appear to play a significant part in
      reflux induced gene expression changes. We postulate that the activation of the
      survival factor NF-kappaB by bile may be linked to the previous cytogenetic data
      from our laboratory showing the amplification of NF-kappaB's chromosome
      (chromosome 4), during Barrett's cancer progression. Hence chromosome 4
      amplification may provide a survival mechanism for bile exposed oesophageal
      tissues via NF-kappaB.

PMID- 14656947
TI  - Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
AB  - Intake of isoflavones derived from soybean products may impact on prostate cancer
      risk. Here we evaluated the effects of Fujiflavone, a commercial isoflavone
      supplement, on rat prostate carcinogenesis induced by 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine in
      cooked meat. F344 male rats were given intragastric administrations of PhIP at
      the dose of 200 mg/kg twice weekly for 10 weeks. The rats subsequently fed a diet
      containing 0.25% Fujiflavone showed a significantly lower incidence of prostate
      carcinomas than those fed a soy-free diet. Interestingly fewer carcinomas but
      more foci of prostatic intra-epithelial neoplasia (PIN) were observed in the
      Fujiflavone group although the sum of the two lesions was not altered by
      Fujiflavone treatment. cDNA array analyses confirmed by semi-quantitative reverse
      transcription polymerase chain reactions (RT-PCR) revealed Fujiflavone to alter
      gene expression of ornithine decarboxylase (ODC), prothymosin alpha (PTA) in the
      rat prostate. No modification of PhIP-induced colon carcinogenesis was evident,
      except for increased multiplicity of aberrant crypt foci >4 crypts in size. These
      results indicate that a commercial isoflavone supplement can inhibit PhIP-induced
      rat prostate carcinogenesis without any adverse effects, possibly by inhibiting
      progression of PIN to carcinoma, and that down-regulation of ODC and PTA could be
      related to the underlying mechanisms. Thus, intake of dietary isoflavones can be
      promising for prevention of human prostate cancer.

PMID- 14656948
TI  - Specific differences in gene expression profile revealed by cDNA microarray
      analysis of glutathione S-transferase placental form (GST-P)
      immunohistochemically positive rat liver foci and surrounding tissue.
AB  - Glutathione S-transferase placental form (GST-P), one of the glutathione S
      transferases family of detoxification enzymes, is a very useful marker of rat
      liver pre-neoplastic lesions. We here investigated the gene expression profile in
      GST-P positive foci as compared with surrounding GST-P negative areas in the same
      liver of rats treated with diethylnitrosamine and then 2-acetylaminofluorene
      combined with partial hepatectomy. GST-P positive foci were harvested by laser
      microdissection and total RNAs were extracted to allow gene expression profiles
      to be assessed by cDNA microarray assays. Transaldolase, rat aflatoxin B1
      aldehyde reductase and gamma-glutamylcysteine synthetase were found as up
      regulated genes and regucalcin as a down-regulated gene, in line with findings
      for hepatocellular carcinomas. The results indicate that the approach adopted is
      useful for understanding mechanisms of hepatocarcinogenesis and identification of
      new markers for rat liver pre-neoplastic foci.

PMID- 14656949
TI  - Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell
      lines.
AB  - To investigate a possible link between bile acids and the pathogenesis of
      pancreatic cancer, we determined whether conjugated or unconjugated bile acids
      induced cyclooxygenase-2 (COX-2) in two human pancreatic cancer cell lines, BxPC
      3 and SU 86.86. Bile acids are known promoters of gastric and colon cancer. We
      demonstrated previously that COX-2, an enzyme that catalyzes the synthesis of
      prostaglandins, is over-expressed in human pancreatic adenocarcinoma. Both human
      pancreatic cell lines were treated with conjugated and unconjugated bile acids.
      COX-2 mRNA and protein were determined. In addition, prostaglandin E2 (PGE2)
      synthesis was measured. Treatment with conjugated or unconjugated bile acids for
      3 h up-regulated COX-2 mRNA. Chenodeoxycholate (CD) or deoxycholate at
      concentrations ranging from 12.5 to 100 micro M caused a dose-dependent induction
      of COX-2 protein with a maximal effect at 100 micro M. Induction of COX-2 protein
      by CD and deoxycholate was detected after treatment for 6 h with maximal
      induction at 12 h. Taurochenodeoxycholate, a conjugated bile acid, also caused
      dose-dependent induction of COX-2 but higher concentrations of bile acid (200
      1200 micro M) were required. Levels of cyclooxygenase-1 were unaffected by bile
      acid treatment. Unconjugated and conjugated bile acids caused 7- and 4-fold
      increases in PGE2 production, respectively. Taken together, these findings
      suggest a possible role for bile acids in the pathogenesis of pancreatic cancer.

PMID- 14656950
TI  - Alpha2-adrenergic receptor-induced vascular constriction in blacks and whites.
AB  - Black Americans have a reduced hypotensive response to the alpha2-adrenergic
      receptor agonist clonidine compared with whites, despite similar central
      sympathoinhibition. This reduced hypotensive response might be explained by
      greater postsynaptic vascular alpha2-adrenergic receptor vasoconstrictive
      response. However, clonidine has a low alpha2/alpha1 selectivity ratio.
      Therefore, to determine the role of altered alpha2-adrenergic receptor vascular
      sensitivity in ethnic differences in vascular response, we compared local
      vascular responses with the highly selective alpha2-adrenergic receptor agonist
      dexmedetomidine in healthy black (n=18) and white (n=19) subjects. Increasing
      doses of dexmedetomidine (0.001 to 1000 ng/min) were infused into a dorsal hand
      vein, and the local response was measured with a linear variable differential
      transformer. Dexmedetomidine caused pronounced venoconstriction, with an average
      (+/-SD) maximum response of 74.5+/-17.72% but with no difference between blacks
      and whites. There was substantial intersubject variability in the sensitivity to
      dexmedetomidine; the dose resulting in 50% (ED50) of maximum vasoconstriction
      ranged from 0.08 ng/min to 256 ng/min. The geometric mean ED50 was 2.28 ng/min
      (95% CI, 0.02 to 271.6 ng/min) in blacks and 1.58 ng/min (95% CI, 0.11 to 24.55
      ng/min) in whites (P=0.59). Our data indicate that alpha2-adrenergic receptor
      induced venoconstriction is similar in blacks and whites. These findings do not
      support the hypothesis that altered alpha2-adrenergic receptor sensitivity is the
      explanation for the decreased blood pressure response to systemic administration
      of clonidine in blacks. The response to dexmedetomidine provides a model that
      will allow further study of the regulation of alpha2-adrenergic receptor-mediated
      vascular responses

PMID- 14656951
TI  - Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive
      patients.
AB  - Hypertensive patients have increased endothelin-1-dependent vasoconstrictor tone.
      This abnormality, however, might not be uniformly present in all forms of
      hypertension, as suggested by experimental studies showing that endothelin-1
      activity is enhanced predominantly in low-renin, high-volume models and in
      insulin-resistant states. Because hypertension in obesity is commonly associated
      with both expanded plasma volume and insulin resistance, this study sought to
      determine whether increased body mass index (BMI) in hypertensive patients
      relates to activation of the endothelin-1 system. Forearm blood flow (FBF)
      responses (plethysmography) to intra-arterial infusion of an ETA receptor blocker
      (BQ-123) were analyzed in hypertensive patients and normotensive control subjects
      according to BMI. The vasodilator response to BQ-123 was significantly higher in
      hypertensive patients than in control subjects (P<0.001). During BQ-123, a
      significant increase in FBF from baseline was observed in obese (BMI > or =30
      kg/m2; P<0.001) and overweight (BMI, 27 to 29.9 kg/m2; P=0.04) but not in lean
      (BMI <27 kg/m2; P=0.83) hypertensive patients. In contrast, no significant change
      in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76),
      or lean (P=0.93) normotensive subjects. Moreover, a significant correlation
      between BMI and the vasodilator response to ETA blockade was observed in
      hypertensive subjects (R=0.53; P=0.005) but not in control subjects (R=0.11;
      P=0.58). In human hypertension, increased BMI is associated with enhanced ETA
      dependent vasoconstrictor activity, suggesting that this abnormality may play a
      role in the pathophysiology of obesity-related hypertension and that targeting
      the endothelin-1 system may be useful in the treatment of these patients.

PMID- 14656952
TI  - Nitric oxide may prevent hypertension early in diabetes by counteracting renal
      actions of superoxide.
AB  - The dependence of blood pressure on a balance between superoxide and nitric oxide
      may be amplified in diabetes. We have shown that the first occurrence of
      sustained hyperglycemia in type I diabetes causes hypertension when induced in
      rats that have had nitric oxide synthesis blocked chronically (L-NAME, 10
      microg/kg per minute IV). This study used tempol (18 micromol/kg per hour IV) to
      test the hypothesis that superoxide mediates that hypertensive response.
      Induction of diabetes in untreated rats had no significant effect on mean
      arterial pressure (MAP, measured 18 h/d), and glomerular filtration rate (GFR)
      increased significantly during the 2 weeks of diabetes. Chronic infusion of L
      NAME in a separate group of rats increased baseline MAP from approximately 90 mm
      Hg to a stable level of approximately 120 mm Hg after 6 days of infusion, and
      induction of diabetes (streptozotocin, 40 mg/kg IV) in those rats caused a rapid,
      progressive increase in MAP that averaged 156+/-5 mm Hg by day 14 of diabetes
      that was associated with a decrease in GFR and 4-fold increase in isoprostane
      excretion. Tempol infusion was begun on day 2 of diabetes in a subgroup of those
      rats, and the progressive hypertensive response was prevented, with MAP averaging
      134+/-10 mm Hg by day 14. In addition, the normal renal hyperfiltration response
      was restored by tempol and the increase in isoprostane did not occur. Thus, the
      hypertension and decrease in GFR caused by onset of diabetes in rats without a
      functioning nitric oxide system was prevented by chronic administration of the
      superoxide dismutase mimetic tempol.

PMID- 14656953
TI  - Determinants of platelet activation in human essential hypertension.
AB  - Experimental data suggest that oxidative stress might be enhanced in hypertension
      and contribute to platelet activation. We hypothesized that both oxidative stress
      and platelet activation could be related to the clinical characteristics of
      hypertensive patients. The urinary excretion of 11-dehydrothromboxane (TX) B2,
      reflecting in vivo platelet activation, was measured in 75 patients with mild to
      severe essential hypertension and 75 pair-matched, healthy controls. The urinary
      excretion of 8-iso-prostaglandin (PG) F2alpha was determined as an index of in
      vivo lipid peroxidation. Urinary 11-dehydro-TXB2 was significantly higher in
      essential hypertensives compared with controls. Although no statistically
      significant difference in urinary 8-iso-PGF2alpha was observed between patients
      and controls, plasma vitamin C was lower and plasma homocysteine higher in
      hypertensive patients than in controls. Both urinary 11-dehydro-TXB2 and 8-iso
      PGF2alpha were higher in patients with advanced hypertensive retinopathy compared
      with patients without retinopathy. Multivariate linear regression analysis
      identified urinary 8-iso-PGF2alpha, plasma fibrinogen, homocysteine, and vitamin
      E as the only variables independently correlated with urinary 11-dehydro-TXB2.
      Logistic regression analysis showed that high urinary 8-iso-PGF2alpha, plasma
      fibrinogen, and homocysteine, as well as low plasma vitamin E, advanced
      retinopathy, elevated diastolic blood pressure, and the absence of
      antihypertensive treatment, were predictors of high urinary 11-dehydro-TXB2. We
      demonstrated increased oxidative stress and persistent platelet activation in
      essential hypertensives with advanced vascular lesions. These findings might help
      identify hypertensive patients who are at increased risk of cardiovascular events
      and who might benefit from long-term antiplatelet therapy.

PMID- 14656955
TI  - Amino-terminal pro-C-type natriuretic peptide in heart failure.
AB  - The levels and pathophysiological role of amino terminal C-type natriuretic
      peptide in heart failure are unknown. The potential of plasma amino-terminal C
      type natriuretic peptide (N-CNP) as a marker of cardiac function was investigated
      in symptomatic patients. In 305 patients with recent-onset dyspnea and/or
      peripheral edema, presenting to primary care, assay of plasma amino-terminal C
      type natriuretic peptide and other plasma vasoactive hormones was conducted
      together with echocardiography. Heart failure was diagnosed in 77 (of the 305)
      patients by rigorous application of predefined criteria. Plasma amino-terminal C
      type natriuretic peptide concentrations were elevated in patients with heart
      failure, and by univariate analysis were related to age, renal function, and
      other hormones. On multivariate analysis, tertile of plasma N-CNP interacted with
      tertile of plasma amino-terminal B-type natriuretic peptide to predict heart
      failure independent of age, gender, renal function, or echocardiographic left
      ventricular fractional shortening. N-CNP showed significant relations to
      concurrent plasma CNP, atrial natriuretic peptide (ANP), N-ANP, B-type (or brain)
      natriuretic peptide (BNP), N-BNP, endothelin-1, and adrenomedullin but not to
      echocardiographic indicators of left ventricular systolic function. Plasma amino
      terminal C-type natriuretic peptide is elevated in heart failure and is related
      to other plasma hormones in heart failure. These findings suggest a possible
      compensatory response from the peripheral vasculature to heart failure by an
      endothelium-based vasodilator peptide and mandate further exploration of the role
      of C-type natriuretic peptide in this condition.

PMID- 14656956
TI  - Hypersensitivity of the adrenal cortex to trophic and secretory effects of
      angiotensin II in Lyon genetically-hypertensive rats.
AB  - In Lyon hypertensive (LH) rats, a model of low-renin genetic hypertension, we
      investigated adrenal sensitivity to angiotensin II in terms of angiotensin II
      receptor (AT1 and AT2 receptors) regulation, morphological changes, and
      aldosterone and corticosterone secretion. Twelve-week-old LH rats, compared with
      normotensive LN and LL rats, were either untreated or treated for 4 weeks with
      AT1 receptor antagonist irbesartan (50 mg/kg/d), angiotensin-converting enzyme
      inhibitor perindopril (3 mg/kg/d), or perindopril (3 mg/kg/d) plus angiotensin II
      infusion (200 ng/kg/min). At 16 weeks, untreated LH rats had high systolic blood
      pressure (P<0.05), low aldosterone (P<0.05), and increased corticosterone
      (P<0.05) plasma levels. AT1-receptor binding density in the zona glomerulosa was
      similar in the three strains. In LH rats, angiotensin II infusion increased the
      relative adrenal weight from 10.5+/-0.3 to 16.7+/-0.7 mg/100g (P<0.05), whereas
      this change was very modest in normotensive rats. Zona glomerulosa enlarged and
      plasma aldosterone increased after angiotensin II infusion in the 3 strains, but
      more markedly in LH versus normotensive rats (2.4- versus 1.3- and 1.6-fold,
      respectively; 20- versus 10-fold in normotensive rats, P<0.05). Surprisingly,
      after angiotensin II infusion, despite the absence of angiotensin II receptors in
      the three strains, the zona fasciculata-reticularis enlarged 1.5-fold and plasma
      corticosterone increased 1.7-fold only in LH rats (P<0.05), suggesting an
      indirect control of this compartment by angiotensin II. The hypertrophy and
      hypersecretory activity of both zona glomerulosa and zona fasciculata-reticularis
      in LH rats in response to angiotensin II point to the adrenal cortex as a pivotal
      tissue in the pathophysiology of hypertension in LH rats.

PMID- 14656957
TI  - Seventh report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure.
AB  - The National High Blood Pressure Education Program presents the complete Seventh
      Report of the Joint National Committee on Prevention, Detection, Evaluation, and
      Treatment of High Blood Pressure. Like its predecessors, the purpose is to
      provide an evidence-based approach to the prevention and management of
      hypertension. The key messages of this report are these: in those older than age
      50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important
      cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75
      mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are
      normotensive at 55 years of age will have a 90% lifetime risk of developing
      hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic
      BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the
      progressive rise in blood pressure and CVD; for uncomplicated hypertension,
      thiazide diuretic should be used in drug treatment for most, either alone or
      combined with drugs from other classes; this report delineates specific high-risk
      conditions that are compelling indications for the use of other antihypertensive
      drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
      blockers, beta-blockers, calcium channel blockers); two or more antihypertensive
      medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg)
      for patients with diabetes and chronic kidney disease; for patients whose BP is
      more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the
      diastolic BP goal, initiation of therapy using two agents, one of which usually
      will be a thiazide diuretic, should be considered; regardless of therapy or care,
      hypertension will be controlled only if patients are motivated to stay on their
      treatment plan. Positive experiences, trust in the clinician, and empathy improve
      patient motivation and satisfaction. This report serves as a guide, and the
      committee continues to recognize that the responsible physician's judgment
      remains paramount.

PMID- 14656958
TI  - Relationship of physical activity and body mass index to the risk of
      hypertension: a prospective study in Finland.
AB  - Prospective studies on physical activity in relation to the risk for hypertension
      are scant, particularly in women. This study aimed at finding out whether regular
      physical activity can reduce the risk of hypertension in both men and women, and
      in subjects with and without overweight. We prospectively followed 8302 Finnish
      men and 9139 women aged 25 to 64 years without a history of antihypertensive drug
      use, coronary heart disease, stroke, and heart failure at baseline. Both single
      and joint associations of physical activity and body mass index with the risk of
      hypertension were examined using Cox proportional hazard models. During a mean
      followup of 11 years, there were 1600 incident cases of drug-treated
      hypertension. Multivariate-adjusted hazards ratios of hypertension associated
      with light, moderate, and high physical activity were 1.00, 0.63, and 0.59 in men
      (Ptrend<0.001), and 1.00, 0.82, and 0.71 in women (Ptrend=0.005), respectively.
      This association persisted both in subjects who were overweight and in those who
      were not. Multivariate-adjusted hazards ratios of hypertension based at different
      levels of body mass index (<25, 25 to 29.9, and > or =30) were 1.00, 1.18, and
      1.66 for men (Ptrend<0.001), and 1.00, 1.24, and 1.32 for women (Ptrend=0.007),
      respectively. Further adjustment for baseline systolic blood pressure did not
      affect the protective effect associated with physical activity, but it weakened
      markedly the association between body mass index and hypertension. The present
      study indicates that regular physical activity and weight control can reduce the
      risk of hypertension. The protective effect of physical activity was observed in
      both sexes regardless of the level of obesity.

PMID- 14656959
TI  - Identification and characterization of multi-species conserved sequences.
AB  - Comparative sequence analysis has become an essential component of studies aiming
      to elucidate genome function. The increasing availability of genomic sequences
      from multiple vertebrates is creating the need for computational methods that can
      detect highly conserved regions in a robust fashion. Towards that end, we are
      developing approaches for identifying sequences that are conserved across
      multiple species; we call these "Multi-species Conserved Sequences" (or MCSs).
      Here we report two strategies for MCS identification, demonstrating their ability
      to detect virtually all known actively conserved sequences (specifically, coding
      sequences) but very little neutrally evolving sequence (specifically, ancestral
      repeats). Importantly, we find that a substantial fraction of the bases within
      MCSs (approximately 70%) resides within non-coding regions; thus, the majority of
      sequences conserved across multiple vertebrate species has no known function.
      Initial characterization of these MCSs has revealed sequences that correspond to
      clusters of transcription factor-binding sites, non-coding RNA transcripts, and
      other candidate functional elements. Finally, the ability to detect MCSs
      represents a valuable metric for assessing the relative contribution of a
      species' sequence to identifying genomic regions of interest, and our results
      indicate that the currently available genome sequences are insufficient for the
      comprehensive identification of MCSs in the human genome.

PMID- 14656960
TI  - Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated
      recombination events during evolution.
AB  - Low-copy repeats, or segmental duplications, are highly dynamic regions in the
      genome. The low-copy repeats on chromosome 22q11.2 (LCR22) are a complex mosaic
      of genes and pseudogenes formed by duplication processes; they mediate chromosome
      rearrangements associated with velo-cardio-facial syndrome/DiGeorge syndrome,
      der(22) syndrome, and cat-eye syndrome. The ability to trace the substrates and
      products of recombination events provides a unique opportunity to identify the
      mechanisms responsible for shaping LCR22s. We examined the genomic sequence of
      known LCR22 genes and their duplicated derivatives. We found Alu (SINE) elements
      at the breakpoints in the substrates and at the junctions in the truncated
      products of recombination for USP18, GGT, and GGTLA, consistent with Alu-mediated
      unequal crossing-over events. In addition, we were able to trace a likely
      interchromosomal Alu-mediated fusion between IGSF3 on 1p13.1 and GGT on 22q11.2.
      Breakpoints occurred inside Alu elements as well as in the 5' or 3' ends of them.
      A possible stimulus for the 5' or 3' terminal rearrangements may be the high
      sequence similarities between different Alu elements, combined with a potential
      recombinogenic role of retrotransposon target-site duplications flanking the Alu
      element, containing potentially kinkable DNA sites. Such sites may represent
      focal points for recombination. Thus, genome shuffling by Alu-mediated
      rearrangements has contributed to genome architecture during primate evolution.

PMID- 14656961
TI  - Does recombination shape the distribution and evolution of tandemly arrayed genes
      (TAGs) in the Arabidopsis thaliana genome?
AB  - Tandemly arrayed genes (TAGs) are an important genomic component. However, most
      previous studies have focused on individual TAG families, and a broader
      characterization of their genomic distribution is not yet available. In this
      study, we examined the distribution of TAGs in the Arabidopsis thaliana genome
      and examined TAG density with relation to recombination rates. Recombination
      rates along A. thaliana chromosomes were estimated by comparing a genetic map
      with the genome sequence. Average recombination rates in A. thaliana are high,
      and rates vary more than threefold among chromosomal regions. Comparisons between
      TAG density and recombination indicate a positive correlation on chromosomes 1,
      2, and 3. Moreover, there is a consistent centromeric effect. Relative to single
      copy genes, TAGs are proportionally less frequent in centromeres than on
      chromosomal arms. We also examined several factors that have been proposed to
      affect the sequence evolution of TAG members. Sequence divergence is related to
      the number of members in the TAG, but genomic location has no obvious effect on
      TAG sequence divergence, nor does the presence of unrelated genes within a TAG.
      Overall, the distribution of TAGs in the genome is not consistent with
      theoretical models predicting the accumulation of repeats in regions of low
      recombination but may be consistent with stabilizing selection models of TAG
      evolution.

PMID- 14656963
TI  - A genome-wide survey of human pseudogenes.
AB  - We screened all intergenic regions in the human genome to identify pseudogenes
      with a combination of homology searches and a functionality test using the ratio
      of silent to replacement nucleotide substitutions (KA/KS). We identified 19,724
      regions of which 95% +/- 3% are estimated to evolve neutrally and thus are likely
      to encode pseudogenes. Half of these have no detectable truncation in their
      pseudocoding regions and therefore are not identifiable by methods that require
      the presence of truncations to prove nonfunctionality. A comparative analysis
      with the mouse genome showed that 70% of these pseudogenes have a
      retrotranspositional origin (processed), and the rest arose by segmental
      duplication (nonprocessed). Although the spread of both types of pseudogenes
      correlates with chromosome size, nonprocessed pseudogenes appear to be enriched
      in regions with high gene density. It is likely that the human pseudogenes
      identified here represent only a small fraction of the total, which probably
      exceeds the number of genes.

PMID- 14656962
TI  - Millions of years of evolution preserved: a comprehensive catalog of the
      processed pseudogenes in the human genome.
AB  - Processed pseudogenes were created by reverse-transcription of mRNAs; they
      provide snapshots of ancient genes existing millions of years ago in the genome.
      To find them in the present-day human, we developed a pipeline using features
      such as intron-absence, frame-disruption, polyadenylation, and truncation. This
      has enabled us to identify in recent genome drafts approximately 8000 processed
      pseudogenes (distributed from http://pseudogene.org). Overall, processed
      pseudogenes are very similar to their closest corresponding human gene, being 94%
      complete in coding regions, with sequence similarity of 75% for amino acids and
      86% for nucleotides. Their chromosomal distribution appears random and dispersed,
      with the numbers on chromosomes proportional to length, suggesting sustained
      "bombardment" over evolution. However, it does vary with GC-content: Processed
      pseudogenes occur mostly in intermediate GC-content regions. This is similar to
      Alus but contrasts with functional genes and L1-repeats. Pseudogenes, moreover,
      have age profiles similar to Alus. The number of pseudogenes associated with a
      given gene follows a power-law relationship, with a few genes giving rise to many
      pseudogenes and most giving rise to few. The prevalence of processed pseudogenes
      agrees well with germ-line gene expression. Highly expressed ribosomal proteins
      account for approximately 20% of the total. Other notables include cyclophilin-A,
      keratin, GAPDH, and cytochrome c.

PMID- 14656964
TI  - From gene networks to gene function.
AB  - We propose a novel method to identify functionally related genes based on
      comparisons of neighborhoods in gene networks. This method does not rely on gene
      sequence or protein structure homologies, and it can be applied to any organism
      and a wide variety of experimental data sets. The character of the predicted gene
      relationships depends on the underlying networks;they concern biological
      processes rather than the molecular function. We used the method to analyze gene
      networks derived from genome-wide chromatin immunoprecipitation experiments, a
      large-scale gene deletion study, and from the genomic positions of consensus
      binding sites for transcription factors of the yeast Saccharomyces cerevisiae. We
      identified 816 functional relationships between 159 genes and show that these
      relationships correspond to protein-protein interactions, co-occurrence in the
      same protein complexes, and/or co-occurrence in abstracts of scientific articles.
      Our results suggest functions for seven previously uncharacterized yeast genes:
      KIN3 and YMR269W may be involved in biological processes related to cell growth
      and/or maintenance, whereas IES6, YEL008W, YEL033W, YHL029C, YMR010W, and YMR031W
      A are likely to have metabolic functions.

PMID- 14656965
TI  - Comparative genome analysis of Vibrio vulnificus, a marine pathogen.
AB  - The halophile Vibrio vulnificus is an etiologic agent of human mortality from
      seafood-borne infections. We applied whole-genome sequencing and comparative
      analysis to investigate the evolution of this pathogen. The genome of biotype 1
      strain, V. vulnificus YJ016, was sequenced and includes two chromosomes of
      estimated 3377 kbp and 1857 kbp in size, and a plasmid of 48,508 bp. A super
      integron (SI) was identified, and the SI region spans 139 kbp and contains 188
      gene cassettes. In contrast to non-SI sequences, the captured gene cassettes are
      unique for any given Vibrio species and are highly variable among V. vulnificus
      strains. Multiple rearrangements were found when comparing the 5.3-Mbp V.
      vulnificus YJ016 genome and the 4.0-Mbp V. cholerae El Tor N16961 genome. The
      organization of gene clusters of capsular polysaccharide, iron metabolism, and
      RTX toxin showed distinct genetic features of V. vulnificus and V. cholerae. The
      content of the V. vulnificus genome contained gene duplications and evidence of
      horizontal transfer, allowing for genetic diversity and function in the marine
      environment. The genomic information obtained in this study can be applied to
      monitoring vibrio infections and identifying virulence genes in V. vulnificus.

PMID- 14656966
TI  - Genomic analysis in the sting-2 quantitative trait locus for defensive behavior
      in the honey bee, Apis mellifera.
AB  - We have sequenced an 81-kb genomic region from the honey bee, Apis mellifera,
      associated with a quantitative trait locus (QTL) sting-2 for aggressive behavior.
      This sequence represents the first extensive study of the honey-bee genome
      structure encompassing putative genes in a QTL for a behavioral trait. Expression
      of 13 putative genes, as well as two transcripts that were present in a honey-bee
      EST database, was confirmed through reverse transcription analysis of mRNA from
      the honey-bee head. Whereas most transcripts exhibited little or no variation
      between European and Africanized honey-bee alleles, one transcript demonstrated
      significant nonsynonymous substitutions, deletions, and insertions. All 13
      putative genes lacked similarity to known invertebrate or vertebrate proteins or
      transcripts. This observation may be reflective of the processes that determine
      the genomic evolution of an insect with social behavior and/or haplo-diploidy and
      are an indication of the unique nature of the honey-bee genome. These results
      make this sequence an invaluable research tool for the ongoing honey-bee whole
      genome sequencing effort.

PMID- 14656968
TI  - Sequence information for the splicing of human pre-mRNA identified by support
      vector machine classification.
AB  - Vertebrate pre-mRNA transcripts contain many sequences that resemble splice sites
      on the basis of agreement to the consensus,yet these more numerous false splice
      sites are usually completely ignored by the cellular splicing machinery. Even at
      the level of exon definition,pseudo exons defined by such false splices sites
      outnumber real exons by an order of magnitude. We used a support vector machine
      to discover sequence information that could be used to distinguish real exons
      from pseudo exons. This machine learning tool led to the definition of potential
      branch points,an extended polypyrimidine tract,and C-rich and TG-rich motifs in a
      region limited to 50 nt upstream of constitutively spliced exons. C-rich
      sequences were also found in a region extending to 80 nt downstream of
      exons,along with G-triplet motifs. In addition,it was shown that combinations of
      three bases within the splice donor consensus sequence were more effective than
      consensus values in distinguishing real from pseudo splice sites; two-way base
      combinations were optimal for distinguishing 3' splice sites. These data also
      suggest that interactions between two or more of these elements may contribute to
      exon recognition,and provide candidate sequences for assessment as intronic
      splicing enhancers.

PMID- 14656967
TI  - Analysis of the gene-dense major histocompatibility complex class III region and
      its comparison to mouse.
AB  - In mammals, the Major Histocompatibility Complex class I and II gene clusters are
      separated by an approximately 700-kb stretch of sequence called the MHC class III
      region, which has been associated with susceptibility to numerous diseases. To
      facilitate understanding of this medically important and architecturally
      interesting portion of the genome, we have sequenced and analyzed both the human
      and mouse class III regions. The cross-species comparison has facilitated the
      identification of 60 genes in human and 61 in mouse, including a potential RNA
      gene for which the introns are more conserved across species than the exons.
      Delineation of global organization, gene structure, alternative splice forms,
      protein similarities, and potential cis-regulatory elements leads to several
      conclusions: (1) The human MHC class III region is the most gene-dense region of
      the human genome: >14% of the sequence is coding, approximately 72% of the region
      is transcribed, and there is an average of 8.5 genes per 100 kb. (2) Gene sizes,
      number of exons, and intergenic distances are for the most part similar in both
      species, implying that interspersed repeats have had little impact in disrupting
      the tight organization of this densely packed set of genes. (3) The region
      contains a heterogeneous mixture of genes, only a few of which have a clearly
      defined and proven function. Although many of the genes are of ancient origin,
      some appear to exist only in mammals and fish, implying they might be specific to
      vertebrates. (4) Conserved noncoding sequences are found primarily in or near the
      5'-UTR or the first intron of genes, and seldom in the intergenic regions. Many
      of these conserved blocks are likely to be cis-regulatory elements.

PMID- 14656969
TI  - Molecular correlates of genes exhibiting RNAi phenotypes in Caenorhabditis
      elegans.
AB  - Understanding genome-wide links between genotype and phenotype has generally been
      difficult due to both the complexity of phenotypes, and until recently,
      inaccessibility to large numbers of genes that might underlie a trait. To address
      this issue, we establish the association between particular RNAi phenotypes in
      Caenorhabditis elegans and sequence characteristics of the corresponding proteins
      and DNA. We find that genes showing RNAi phenotypes are long and highly expressed
      with little noncoding DNA and high rates of synonymous site substitution (KS). In
      addition, genes conferring RNAi phenotypes have significantly lower rates of
      nonsynonymous site substitution (KA). Collectively, these sequence features
      explain nearly 20% of the difference between the sets of loci that display or
      lack a RNAi-mediated effect, and reflect aspects both of the RNAi mechanism and
      the biological function of the genes. For example, the particularly low rate of
      evolution of genes in the sterility RNAi phenotype class suggests a role of C.
      elegans life history in shaping these patterns of sequence and expression
      characteristics on phenotypes. This approach also allows prediction of a set of
      heretofore-uncharacterized loci for which we expect future RNAi studies to reveal
      phenotypic effects (i.e., false negatives in present screens).

PMID- 14656970
TI  - Genes and transposons are differentially methylated in plants, but not in
      mammals.
AB  - DNA methylation is found in many eukaryotes, but its function is still
      controversial. We have studied the methylation of plant and animal genomes using
      a PCR-based technique amenable for high throughput. Repetitive elements are
      methylated in both organisms, but whereas most mammalian exons are methylated,
      plant exons are not. Thus, targeting of methylation specifically to transposons
      appears to be restricted to plants. We propose that the mechanistic basis of this
      difference may involve RNA interference. Sequencing strategies that depend on
      differential methylation are predicted to have different outcomes in plant and
      mammalian genomes.

PMID- 14656971
TI  - Hierarchy of sequence-dependent features associated with prokaryotic translation.
AB  - Protein expression in the cell is affected by various sequence-dependent
      features. Several such sequence-dependent features have been individually
      studied,yet they have not been compared quantitatively in terms of their relative
      influence on protein expression,and a hierarchy of these elements has not been
      determined. Here we present a quantitative analysis examining sequence-dependent
      features involved in prokaryotic translation,namely,the base-pairing potential
      between the mRNA Shine-Dalgarno sequence and the ribosomal RNA,codon bias,and the
      identity of the stop codon. We analyzed these features both at intra- and
      intergenomic levels using the Escherichia coli and Haemophilus influenzae
      genomes. Within each genome,we examined the relationship between each feature and
      protein expression levels determined by 2D-gel analyses. At the intergenomic
      level,comparative genomic principles were applied to study the relative
      preservation of the different sequence-dependent properties between orthologs.
      From these analyses,we determined that biased codon usage is the property that is
      most highly associated with protein expression and that is most conserved. The
      identity of the stop codon and the base-pairing potential of the mRNA Shine
      Dalgarno sequence and the rRNA seem to have less of an effect on protein
      expression.

PMID- 14656972
TI  - The clustered olfactory receptor gene family 262: genomic organization, promotor
      elements, and interacting transcription factors.
AB  - For six mouse olfactory receptor genes from family 262 which are expressed in
      clustered populations of olfactory sensory neurons, the genomic as well as cDNA
      structures were deciphered. All genes contained several exons which in some cases
      were alternatively spliced. Immediately upstream of the transcription start
      sites, sequence motif blocks were identified that are highly conserved among
      olfactory receptor (OR) genes which are expressed in clustered neuronal
      populations. By means of electrophoretic mobility shift assays, it was
      demonstrated that segments of the motif block region interact with proteins
      extracted from nuclear fractions of the olfactory epithelium. Yeast one-hybrid
      screenings of an olfactory cDNA library led to the identification of a set of
      transcription factors that specifically bind to particular elements of the motif
      block region. The identified factors can be categorized into two types: One group
      is known to be involved in transcriptional initiation, and the second group
      represents factors involved in pattern formations. The identified components may
      contribute to govern the precise topographic expression pattern of olfactory
      receptor genes.

PMID- 14656974
TI  - Clone-based systematic haplotyping (CSH): a procedure for physical haplotyping of
      whole genomes.
AB  - We present a novel methodology to determine the phase of single-nucleotide
      polymorphisms (SNPs) on a chromosome, which we term clone-based systematic
      haplotyping (CSH). The CSH procedure is based on separating the allelic
      chromosomes of a diploid genome by fosmid/cosmid cloning, and subsequent SNP
      typing of 96 clone pools, each representing approximately 10% of the genome. The
      pools are screened by PCR for the sequence of interest, followed by SNP typing on
      the PCR products using the GOOD assay. We demonstrate that by CSH, the haplotype
      of SNPs separated by more than 50 kilobases can definitely be assigned. We
      propose this method as being suitable for constructing maps of ancestral
      haplotypes, analysis of complex diseases, and for diagnosis of rare defects in
      which the molecular haplotype is crucial. In addition, by amplifying the initial
      DNA by many orders of magnitude, the original DNA resource is effectively
      immortalized, enabling the haplotyping of hundreds of thousands of SNPs per
      individual.

PMID- 14656973
TI  - Toward a functional annotation of the human genome using artificial transcription
      factors.
AB  - We have developed a novel, high-throughput approach to collecting randomly
      perturbed gene-expression profiles from the human genome.A human 293 cell library
      that stably expresses randomly chosen zinc-finger transcription factors was
      constructed, and the expression profile of each cell line was obtained using cDNA
      microarray technology.Gene expression profiles from a total of 132 cell lines
      were collected and analyzed by (1) a simple clustering method based on expression
      profile similarity, and (2) the shortest-path analysis method. These analyses
      identified a number of gene groups, and further investigation revealed that the
      genes that were grouped together had close biological relationships. The
      artificial transcription factor-based random genome perturbation method thus
      provides a novel functional genomic tool for annotation and classification of
      genes in the human genome and those of many other organisms.

PMID- 14656976
TI  - A BAC-based physical map of the chicken genome.
AB  - A genome-wide physical map constructed with bacterial artificial chromosomes
      (BACs) is an essential component in linking phenotypic traits to the responsible
      genetic variation in the genomes of plants and animals. We have constructed a
      physical map of the chicken genome from 57,091 BACs (7.9-fold haploid genome
      coverage) by restriction fingerprint analysis using high-resolution
      polyacrylamide gel electrophoresis. The physical map consists of 2331 overlapping
      BAC contigs and is estimated to span 1510 Mb in physical length. BAC contigs were
      verified manually and by screening the BACs with 367 DNA markers. A total of 361
      of the contigs have been anchored to the existing chicken genetic map. This map
      represents the first genome-wide, BAC-based physical map of the chicken genome.
      It provides a powerful platform for many areas of chicken genomics, including
      targeted marker development, fine mapping of genes and QTL alleles, positional
      cloning, analysis of avian genome organization and evolution, chicken-mammalian
      comparative genomics, and large-scale genome sequencing.

PMID- 14656977
TI  - COX-3--a virtual pain target in humans?

PMID- 14656978
TI  - Integrated evolutionary, immunological, and neuroendocrine framework for the
      pathogenesis of chronic disabling inflammatory diseases.
AB  - The pathogenesis of chronic disabling inflammatory diseases (CDIDs) is poorly
      understood. Current concepts that focus on abnormalities of the immune system
      are, in our view, incomplete. Here we propose that chronic disruption of
      homeostasis through abnormal neuronal and endocrine host responses to transient
      inflammatory reactions contributes to the appearance of CDIDs. Coordinated
      reactions of the supersystems (immune, nervous, endocrine, and reproductive) that
      maintain homeostasis have been evolutionarily conserved to respond to and
      eliminate foreign agents over a period of days to a few weeks. If the responses
      of these supersystems fail to return to normal after elimination of the pathogen,
      a continuous aggressive immune response is created; this situation can trigger
      development of CDIDs. Maladaptation of the supersystems during CDIDs has not been
      evolutionarily conserved but is nevertheless still prevalent because a large
      proportion of these diseases tend to appear after the reproductive phase. We
      propose that this integrated systems hypothesis may permit better identification
      of a patient at risk or in the early stages of developing a CDID such as
      rheumatoid arthritis and enable more coordinated intervention than is presently
      attempted.

PMID- 14656979
TI  - Pyridoxal 5'-phosphate as a novel weapon against autoimmunity and transplant
      rejection.
AB  - Activation of CD4 T cells by antigen-presenting cells is required for the full
      expression of most autoimmune diseases and allogeneic transplant rejection. The
      extracellular part of CD4 molecule is composed of four domains, D1-D4. CD4 binds
      to MHC class II via its D1 and D2 domains. Pyridoxal 5'-phosphate (PLP) binds
      very tightly to the D1 domain of CD4 and therefore could interfere with proper
      CD4-MHC II interaction. Nonincorporation of CD4 into the activation complex can
      result in T cell apoptosis and anergy to autoantigen (s). Occupancy of D1 by PLP
      may prevent the proper protein-protein interactions of the CD4 molecule itself,
      which are important in T cell activation. PLP may also interfere with the
      dimerization of CD4 molecules, which occurs during T cell activation, or with the
      interaction of this dimer with other molecules on the T cell surface, such as
      CD45, thereby further rendering T cells anergic or driven to apoptosis.
      Therefore, PLP may have utility in the treatment of autoimmunity and transplant
      rejection. Furthermore, as the interaction of the HIV gp120 and CD4 occurs via
      D1, PLP is supposed to have anti-HIV effect as well. PLP may prove of special
      utility in the treatment of patients affected with both autoimmunity and HIV, for
      whom the routine immunosuppressives are contraindicated.

PMID- 14656980
TI  - NF-kappaB activation pathways induced by T cell costimulation.
AB  - Analysis of knockout mice and of T cells deficient for individual signaling
      proteins allowed the identification of novel members of the costimulation-induced
      NF-kappaB activation pathway while biochemical approaches started to unveil their
      functional mechanisms. These results show that NF-kappaB activation depends on an
      early wave of tyrosine phosphorylation that allows the inducible formation of
      multiprotein complexes containing several proteins required for NF-kappaB
      activation: adaptor proteins including Src homology 2 domain-containing leukocyte
      phosphoprotein 76 (SLP-76) and proteins with enzymatic activity, such as
      phospholipase C (PLC) gamma and the exchange factor Vav1. While Vav1 contributes
      to Rac-dependent reorganization of the actin cytoskeleton, activated PLCgamma1
      generates the protein kinase C (PKC) activator diacylglycerol. In T cells, the
      novel PKC isoform PKCtheta is indispensable for NF-kappaB activation and its
      enzymatic activity depends on recruitment to the immunological synapse.
      Downstream from PKCtheta, the caspase recruitment domain (CARD) proteins
      CARD11/CARMA1 and Bcl10 relay T cell receptor-derived signals to the IkappaB
      kinase (IKK) complex. Many members of the NF-kappaB activation cascade, including
      the IKKs, are either constitutively or inducibly translocated to the lipid raft
      fraction, showing a highly organized spatial distribution of these NF-kappaB
      activating proteins.

PMID- 14656981
TI  - Nitric oxide produced in rat liver mitochondria causes oxidative stress and
      impairment of respiration after transient hypoxia.
AB  - Nitric oxide (NO) is produced in mammals by different isoforms of NO synthase
      (NOS), including the constitutive mitochondrial enzyme (mtNOS). Here we
      demonstrate that the concentration of NO resulting from a mitochondrial NOS
      activity increases under hypoxic conditions in isolated rat liver mitochondria.
      We show that mitochondrially derived NO mediates the impairment of active (state
      3) respiration as measured in the presence of the substrates glutamate and malate
      after reoxygenation. Simultaneously, NO induces oxidative stress in mitochondria,
      characterized by an increase in the amount of protein carbonyls and a decrease in
      glutathione (GSH). Both the accumulation of oxidative stress markers during and
      the impaired respiration after reoxygenation were prevented by blocking NO
      production with the NOS inhibitor L-NAME. These observations suggest that
      mitochondria are exposed to high amounts of NO generated by a mitochondrial NOS
      upon hypoxia/reoxygenation. Such increased NO levels, in turn, inhibit
      mitochondrial respiration and may cause oxidative stress that leads to
      irreversible impairment of mitochondria.

PMID- 14656982
TI  - Role of reactive oxygen species and cardiolipin in the release of cytochrome c
      from mitochondria.
AB  - Several lines of evidence indicate that mitochondria-mediated reactive oxygen
      species (ROS) generation is a major source of oxidative stress in the cell.
      Release of cytochrome c from mitochondria is a central event in apoptosis
      induction and appears to be mediated by ROS. Dissociation of cytochrome c from
      the IMM, where it is bound to cardiolipin, represents a necessary first step for
      cytochrome c release. In the present study, the role of ROS and cardiolipin in
      the release of cytochrome c from rat liver mitochondria was investigated. ROS
      were produced by mitochondria oxidizing succinate in the nonphosphorylating
      state. Cytochrome c was quantitated by a new, very sensitive and rapid reverse
      phase HPLC method. We found that succinate-supported ROS production resulted in a
      release of cytochrome c from mitochondria and a parallel loss of cardiolipin
      content. These effects were directly and significantly correlated and also
      abolished by ADP, which prevents succinate-mediated ROS production. The ROS
      induced cytochrome c release was independent from MPT and appears to involve
      VDAC. It is suggested that mitochondrial-induced ROS production promotes
      cytochrome c release from mitochondria by a two-steps process, consisting of the
      dissociation of this protein from cardiolipin, followed by permeabilization of
      the outer membrane, probably by interaction with VDAC. The data may help clarify
      the molecular mechanism underlying the release of cytochrome c from the
      mitochondria to the cytosol and the role of ROS and cardiolipin in this release.

PMID- 14656983
TI  - Isolevuglandins, a novel class of isoprostenoid derivatives, function as
      integrated sensors of oxidant stress and are generated by myeloperoxidase in
      vivo.
AB  - Isolevuglandins (isoLGs) are a family of reactive gamma-ketoaldehydes generated
      by free radical oxidation of arachidonate-containing lipids through the
      isoprostane pathway. Elevated plasma levels of isoLG protein adducts are observed
      in subjects with atherosclerosis compared with age/gender-matched controls.
      However, mechanisms for the generation of isoLGs in vivo are not established.
      Here we show that free radical-induced peroxidation promoted by the
      myeloperoxidase (MPO)/H2O2 system of leukocytes serves as one mechanism for the
      generation of isoLGs in vivo. Using a Candida sepsis model of inflammation, we
      demonstrate 3.5- and 2.7-fold increases in iso[4]LGE2 and isoLGE2 adducts of
      plasma proteins after pathogen exposure in wild-type mice. Plasma levels of F2
      isoprostanes were not significantly increased after pathogen challenge in this
      model. MPO knockout mice demonstrated significant reductions (34%, P=0.003) in
      plasma levels of iso[4]LGE2 protein adducts after pathogen challenge compared
      with wild-type mice. Mass spectrometry and immunochemical methods demonstrate MPO
      dependent formation of iso[4]LGE2 and isoLGE2 phospholipids and their
      corresponding isoLG protein adducts in model systems. The present studies thus
      identify MPO as one pathway for generation of isoLGs in vivo. They also suggest
      that long-lived protein isoLG adducts may serve as an alternative integrated
      sensor of oxidant stress in vivo.

PMID- 14656975
TI  - Generation, annotation, evolutionary analysis, and database integration of 20,000
      unique sea urchin EST clusters.
AB  - Together with the hemichordates, sea urchins represent basal groups of
      nonchordate invertebrate deuterostomes that occupy a key position in bilaterian
      evolution. Because sea urchin embryos are also amenable to functional studies,
      the sea urchin system has emerged as one of the leading models for the analysis
      of the function of genomic regulatory networks that control development. We have
      analyzed a total of 107,283 cDNA clones of libraries that span the development of
      the sea urchin Strongylocentrotus purpuratus. Normalization by oligonucleotide
      fingerprinting, EST sequencing and sequence clustering resulted in an EST catalog
      comprised of 20,000 unique genes or gene fragments. Around 7000 of the unique EST
      consensus sequences were associated with molecular and developmental functions.
      Phylogenetic comparison of the identified genes to the genome of the urochordate
      Ciona intestinalis indicate that at least one quarter of the genes thought to be
      chordate specific were already present at the base of deuterostome evolution.
      Comparison of the number of gene copies in sea urchins to those in chordates and
      vertebrates indicates that the sea urchin genome has not undergone extensive gene
      or complete genome duplications. The established unique gene set represents an
      essential tool for the annotation and assembly of the forthcoming sea urchin
      genome sequence. All cDNA clones and filters of all analyzed libraries are
      available from the resource center of the German genome project at
      http://www.rzpd.de.

PMID- 14656984
TI  - Macrophage migration inhibitory factor delays apoptosis in neutrophils by
      inhibiting the mitochondria-dependent death pathway.
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine known
      to activate macrophages and T cells. In this study, we demonstrate that
      recombinant MIF delays apoptosis of neutrophils in vitro. MIF action is dose and
      time dependent as well as specific since it was abolished with a neutralizing
      anti-MIF antibody. MIF, like G-CSF, delayed cleavage of the proapoptotic members
      of the Bcl-2 family Bid and Bax in neutrophils, suggesting that MIF inhibits
      apoptosis pathways proximal to mitochondria activation. Indeed, MIF also
      prevented release of cytochrome c and Smac from the mitochondria and subsequent
      activation of the critical effector caspase-3 in these cells. Moreover, we
      observed increased MIF plasma levels in patients with cystic fibrosis, a
      heterogeneous recessive genetic disorder associated with bacterial infections and
      delayed neutrophil apoptosis. In conclusion, MIF is a survival cytokine for human
      neutrophils, a finding with potential pathologic relevance in infectious
      diseases.

PMID- 14656985
TI  - Cardiomyocytes overexpressing TNF-alpha attract migration of embryonic stem cells
      via activation of p38 and c-Jun amino-terminal kinase.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the
      pathogenesis of myocardial infarction. Stem cells are able to regenerate
      infarcted myocardium. This study investigated whether TNF-alpha was able to
      induce migration of embryonic stem cells (ESCs) in vitro. We used a Transwell
      assay in which neonatal rat cardiomyocytes, with or without transfection of TNF
      alpha cDNA, were plated in the lower compartments and mouse ESCs tagged with
      green fluorescent protein were added to the upper compartments. TNF-alpha level
      was significantly increased in the medium of the lower compartments seeded with
      TNF-alpha-transfected cardiomyocytes. Compared with the controls, overexpression
      of TNF-alpha significantly enhanced migration of ESCs to the lower compartments.
      This enhancement was attenuated by preincubation of ESCs with the antibody
      against the type II TNF-alpha receptor (TNF-RII), but not by the antibody against
      the type I TNF-alpha receptor (TNF-RI). Western blot analysis showed that the
      phosphorylated protein levels of p38 and c-Jun amino-terminal kinase (JNK) were
      significantly increased in TNF-alpha-treated ESCs. Inhibition of the activity of
      p38 or JNK significantly attenuated TNF-alpha-induced ESC migration. Our data
      demonstrate that excessive TNF-alpha stimulates TNF-RII and enhances migration of
      ESCs in vitro. Activation of p38 and JNK is required for TNF-alpha-enhanced ESC
      migration.

PMID- 14656986
TI  - Involvement of site-specific FAK phosphorylation in sphingosine-1 phosphate- and
      thrombin-induced focal adhesion remodeling: role of Src and GIT.
AB  - Sphingosine-1 phosphate (S1P) and thrombin are agents with profound but divergent
      effects on vascular endothelial cell (EC) barrier properties. We have previously
      reported that S1P-induced focal adhesion (FA) remodeling involves interactions
      between focal adhesion kinase (FAK), paxillin, and G-protein-coupled receptor
      kinase-interacting proteins GIT1 and GIT2 and suggested a critical involvement of
      focal adhesions in the EC barrier regulation. In this study, we examined
      redistribution of FA proteins (FAK, paxillin, GIT1, and GIT2) and site-specific
      FAK tyrosine phosphorylation in human pulmonary artery endothelial cells
      stimulated with thrombin. In contrast to S1P, which we have shown to induce
      peripheral translocation of FA proteins associated with cortical actin ring
      formation, thrombin caused the redistribution of FA proteins to the ends of the
      newly formed massive stress fibers. S1P and thrombin induced distinct patterns of
      FAK site-specific phosphorylation with the FAK Y576 phosphorylation site targeted
      by SIP challenge and phosphorylation of three FAK sites (Y397, Y576, and Y925) in
      response to thrombin stimulation. Pharmacological inhibition of Src with Src
      specific inhibitor PP2 abolished S1P-induced translocation of FA proteins,
      cortical actin ring formation, and FAK [Y576] phosphorylation. However, PP2
      failed to alter thrombin-induced morphological changes and exhibited only partial
      inhibition of FAK site-specific tyrosine phosphorylation. These observations
      highlight the differential mechanisms of focal adhesion protein complex
      remodeling and FAK activation by S1P and thrombin and link differential FA
      remodeling to EC barrier regulation.

PMID- 14656987
TI  - Engraftment of a vascularized human skin equivalent.
AB  - Clinical performance of currently available human skin equivalents is limited by
      failure to develop perfusion. To address this problem we have developed a method
      of endothelial cell transplantation that promotes vascularization of human skin
      equivalents in vivo. Enhancement of vascularization by Bcl-2 overexpression was
      demonstrated by seeding human acellular dermis grafts with human umbilical vein
      endothelial cells (HUVEC) transduced with the survival gene Bcl-2 or an EGFP
      control transgene, and subcutaneous implantation in immunodeficient mice (n=18).
      After 1 month the grafts with Bcl-2-transduced cells contained a significantly
      greater density of perfused HUVEC-lined microvessels (55.0/mm3) than controls
      (25.4/mm3,P=0.026). Vascularized skin equivalents were then constructed by
      sequentially seeding the apical and basal surfaces of acellular dermis with
      cultured human keratinocytes and Bcl-2-transduced HUVEC, respectively. Two weeks
      after orthotopic implantation onto mice, 75% of grafts (n=16) displayed both a
      differentiated human epidermis and perfusion through HUVEC-lined microvessels.
      These vessels, which showed evidence of progressive maturation, accelerated the
      rate of graft vascularization. Successful transplantation of such vascularized
      human skin equivalents should enhance clinical utility, especially in recipients
      with impaired angiogenesis.

PMID- 14656990
TI  - Early vitamin E supplementation in young but not aged mice reduces Abeta levels
      and amyloid deposition in a transgenic model of Alzheimer's disease.
AB  - Increased brain oxidative stress is a key feature of Alzheimer's disease (AD) and
      manifests predominantly as lipid peroxidation. However, clinical evidence that
      antioxidants can affect the clinical course of the disease is limited. In the
      present study, we investigated the effect of the antioxidant Vitamin E on the AD
      like phenotype when given to a transgenic mouse model (Tg2576) of the disease
      before or after the amyloid plaques are deposited. One group of Tg2576 received
      Vitamin E starting at 5 months of age until they were 13 months old, the second
      group started at 14 months of age until they were 20 months old. Brain levels of
      8,12-iso-iPF2alpha-VI, a specific marker of lipid peroxidation, were
      significantly reduced in both groups of mice receiving Vitamin E compared with
      placebo. Tg2576 administered with Vitamin E at a younger age showed a significant
      reduction in Abeta levels and amyloid deposition. By contrast, mice receiving the
      diet supplemented with Vitamin E at a later age did not show any significant
      difference in either marker when compared with placebo. These results support the
      hypothesis that oxidative stress is an important early event in AD pathogenesis,
      and antioxidant therapy may be beneficial only if given at this stage of the
      disease process.

PMID- 14656991
TI  - Axonal transport of British and Danish amyloid peptides via secretory vesicles.
AB  - The ABri and ADan amyloid peptides deposited in familial British and Danish
      neurodegenerative disorders are generated by processing mutant forms of the
      precursor protein BRI2. Although the pathogenic process that leads to deposition
      of amyloid in the brains of patients has been studied extensively, the cellular
      processes and normal function of the precursor protein did not receive much
      attention. We observed in a variety of transfected cell lines the presence of two
      independent proteolytic processing events. In addition to the previously
      described cleavage, which results in the production of carboxyl-terminal
      approximately 3 kDa wild-type peptide or approximately 4 kDa ABri or ADan
      peptides, we describe a novel amino-terminal cleavage site within BRI2. Both
      cleavages occur within the cis- or medial-Golgi. Following cleavage, the BRI2
      derived carboxyl-terminal peptides are transported via a regulated secretory
      pathway into secretory vesicles in neuronal cells. Worth noting is that
      expression of wild-type British or Danish mutants of BRI2, in mouse neuroblastoma
      N2a cells that do not express endogenous BRI2, induces elongation of neurites,
      which suggests a role for this protein in differentiation of neuronal cells.

PMID- 14656992
TI  - Hair growth induction by the Tellurium immunomodulator AS101: association with
      delayed terminal differentiation of follicular keratinocytes and ras-dependent up
      regulation of KGF expression.
AB  - The synthetic immunomodulator AS101[ammonium trichloro(dioxoethylene
      o,o')tellurate] was previously found to protect cancer patients from chemotherapy
      induced bone marrow toxicity and alopecia. Here we show that AS101 induces hair
      growth in nude and normal mice. AS101 possesses the dual ability to both induce
      anagen and retard spontaneous catagen in the C57BL/6 mouse model. Anagen induced
      by AS101 is mediated by keratinocyte growth factor (KGF), as it is abrogated both
      in nude mice co-treated with AS101 plus neutralizing anti KGF antibodies and in
      AS101-treated transgenic mice expressing a dominant-negative KGF receptor
      transgene in basal keratinocytes. AS101 up-regulates KGF expression by activating
      the ras signaling pathway in cultured fibroblasts. AS101-induced delayed catagen
      is associated with inhibition of terminal differentiation marker expression both
      in nude and C57BL/6 mice epidermal follicular keratinocytes and in cultures of
      primary mouse follicular keratinocytes induced to differentiate. This activity is
      associated with relatively sustained elevation of p21waf. Delayed expression of
      terminal differentiation markers was not induced by AS101 in follicular
      keratinocytes from p21waf knockout mice. Because similar results were obtained
      with cultures of primary human keratinocytes and fibroblasts, preliminary case
      report studies revealed substantial hair growth when AS101 was topically applied
      on three adolescents who had remained alopeciac 1-2 years after chemotherapy. The
      results emphasize the unique mode of action of AS101 and highlight its potential
      clinical use for treating certain types of alopecia.

PMID- 14656993
TI  - Cross-talk between vascular endothelial growth factor and semaphorin-3A pathway
      in the regulation of normal and malignant mesothelial cell proliferation.
AB  - Vascular endothelial growth factor (VEGF) and semaphorin-3A (Sema-3A) play
      important roles in the transduction of promitotic and antimitotic signals,
      respectively. Here, we report that these conflicting signals are integrated via
      negative feedback between VEGF and Sema-3A pathways in several primary normal,
      but not malignant, mesothelial cells. Unlike malignant mesothelial (MM) cells, in
      which VEGF induces cell proliferation, normal mesothelial (NM) cell growth was
      repressed by VEGF. Although both cell-types expressed an overlapping set of VEGF
      tyrosine-kinase receptors, only in NM cells VEGF exposure entails a p38 mitogen
      activated protein kinase (MAPK)-dependent increased of Sema-3A production.
      Inhibition of p38 MAPK (by SB202190 and SB203580) or a dominant-negative mutant
      of Sema-3A receptor plexin-A1 reversed the inhibitory effects of VEGF in NM
      cells, increasing cyclin D1 synthesis and cell growth. Conversely, sustained
      activation of p38 MAPK by the p38 MAPK-activating kinases MKK3 and MKK6 or
      transfection with Sema-3A inhibited VEGF-induced cyclin D1 up-regulation and MM
      cell proliferation. Therefore, these results delineate a new role of Sema-3A in
      VEGF function mediated by p38 MAPK and suggest that the abrogation of regulated
      Sema-3A expression is responsible for VEGF-driven growth of tumor cells.

PMID- 14656995
TI  - Cell entry and antimicrobial properties of eukaryotic cell-penetrating peptides.
AB  - Antimicrobial drug action is limited by both microbial and host cell membranes.
      Microbes stringently exclude the entry of most drugs, and mammalian membranes
      limit drug distribution and access to intracellular pathogens. Recently, cell
      penetrating peptides (CPPs) have been developed as carriers to improve mammalian
      cell uptake. Given that CPPs are cationic and often amphipathic, similar to
      membrane active antimicrobial peptides, it may be possible to use CPP activity to
      improve drug delivery to microbes. Here, two CPPs, TP10 and pVEC, were found to
      enter a range of bacteria and fungi. The uptake route involves rapid surface
      accumulation within minutes followed by cell entry. TP10 inhibited Candida
      albicans and Staphylococcus aureus growth, and pVEC inhibited Mycobacterium
      smegmatis growth at low micromolar doses, below the levels that harmed human HeLa
      cells. Therefore, although TP10 and pVEC entered all cell types tested, they
      preferentially damage microbes, and this effect was sufficient to clear HeLa cell
      cultures from noninvasive S. aureus infection. Also, conversion of the
      cytotoxicity indicator dye SYTOX Green showed that TP10 causes rapid and lethal
      permeabilization of S. aureus and pVEC permeabilizes M. smegmatis, but not HeLa
      cells. Therefore, TP10 and pVEC can enter both mammalian and microbial cells and
      preferentially permeabilize and kill microbes.

PMID- 14656994
TI  - Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the
      injured vessel wall in vivo.
AB  - Platelet-collagen interactions play a fundamental role in the process of arterial
      thrombosis. The major platelet collagen receptor is the glycoprotein VI (GPVI).
      Here, we determined the effects of a soluble dimeric form of GPVI on platelet
      adhesion in vitro and in vivo. We fused the extracellular domain of GPVI with the
      human immunoglobulin Fc domain. The soluble dimeric form of GPVI (GPVI-Fc)
      specifically bound to immobilized collagen. Binding of GPVI-Fc to collagen was
      inhibited competitively by soluble GPVI-Fc, but not control Fc lacking the
      external GPVI domain. GPVI-Fc inhibited the adhesion of CHO cells that stably
      express human GPVI and of platelets on collagen and attenuated thrombus formation
      under shear conditions in vitro. To test the effects of GPVI-Fc in vivo, arterial
      thrombosis was induced in the mouse carotid artery, and platelet-vessel wall
      interactions were visualized by intravital fluorescence microscopy. Infusion of
      GPVI-Fc but not of control Fc virtually abolished stable arrest and aggregation
      of platelets following vascular injury. Importantly, GPVI-Fc but not control Fc,
      was detected at areas of vascular injury. These findings further substantiate the
      critical role of the collagen receptor GPVI in the initiation of thrombus
      formation at sites of vascular injury and identify soluble GPVI as a promising
      antithrombotic strategy.

PMID- 14656996
TI  - Sertoli cell modulates MAA-induced apoptosis of germ cells throughout voltage
      operated calcium channels.
AB  - Spontaneous cell death by apoptosis--occurring during normal spermatogenesis in
      mammals--is a prominent event, which results in the loss of up to 75% of the
      potential number of mature spermatozoa. In the rat testis, the most conspicuous
      dying cells are pachytene spermatocytes, which are also the primary target of the
      apoptosis experimentally induced by methoxyacetic acid (MAA). In this paper, we
      have used clusterin expression as an indicator of germ cell apoptosis in rat
      seminiferous tubules treated with MAA in the presence or in the absence of
      voltage-operated calcium channels (VOCCs) inhibitors. We performed both a
      qualitative analysis of clusterin expression by immunofluorescence experiments
      and a quantitative analysis of apoptosis by in situ end labeling of apoptotic
      germ cells followed by flow cytometry. The results obtained demonstrate that
      Sertoli cells, the somatic component of the seminiferous epithelium, which
      control male germ cell differentiation, also modulate MAA-induced apoptosis of
      germ cells throughout voltage-operated calcium channels.

PMID- 14656997
TI  - Combined cDNA array/RT-PCR analysis of gene expression profile in rat
      gastrocnemius muscle: relation to its adaptive function in energy metabolism
      during fasting.
AB  - We evaluated the effects of fasting on the gene expression profile in rat
      gastrocnemius muscle using a combined cDNA array and RT-PCR approach. Of the 1176
      distinct rat genes analyzed on the cDNA array, 114 were up-regulated more than
      twofold in response to fasting, including all 17 genes related to lipid
      metabolism present on the membranes and all 10 analyzed components of the
      proteasome machinery. Only 7 genes were down-regulated more than twofold. On the
      basis of our analysis of genes on the cDNA array plus the data from our RT-PCR
      assays, the metabolic adaptations shown by rat gastrocnemius muscle during
      fasting are reflected by i) increased transcription both of myosin heavy chain
      (MHC) Ib (associated with type I fibers) and of at least three factors involved
      in the shift toward type I fibers [p27kip1, muscle LIM protein (MLP), cystein
      rich protein-2], of which one (MLP) has been shown to enhance the activity of
      MyoD, which would explain the known increase in the expression of skeletal muscle
      uncoupling protein-3 (UCP3); ii) increased lipoprotein lipase (LPL) expression,
      known to trigger UCP3 transcription, which tends, together with the first point,
      to underline the suggested role of UCP3 in mitochondrial lipid handling (the
      variations under the first point and this one have not been observed in mice,
      indicating a species-specific regulation of these mechanisms); iii) reduced
      expression of the muscle-specific coenzyme Q (CoQ)7 gene, which is necessary for
      mitochondrial CoQ synthesis, together with an increased expression of
      mitochondrial adenylate kinase 3, which inactivates the resident key enzyme for
      CoQ synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the mRNA level
      for which fell during fasting; and iv) increased transcription of components of
      the proteasomal pathways involved in protein degradation/turnover.

PMID- 14656999
TI  - Identification of Na+/H+ exchange as a new target for toxic polycyclic aromatic
      hydrocarbons.
AB  - The ubiquitous environmental pollutants polycyclic aromatic hydrocarbons are
      responsible for important carcinogenic and apoptotic effects, whose mechanisms
      are still poorly understood, owing to the multiplicity of possible cellular
      targets. Among these mechanisms, alterations of ionic homeostasis have been
      suggested. In this work, the effects of benzo(a)pyrene [B(a)P] on pHi were tested
      in the rat liver F258 epithelial cell line, using the fluoroprobe carboxy-SNARF
      1. After a 48-h treatment, B(a)P (50 nM) induced an alkalinization, followed by
      an acidification after 72 h and the development of apoptosis. Determinations of
      pH(i) recovery following an acid load showed an increased acid efflux at 48 h.
      Cariporide inhibited both the early alkalinization and the increased acid efflux,
      thus suggesting the involvement of Na+/H+ exchanger 1 (NHE1). Besides, alpha
      naphtoflavone (alpha-NF), an inhibitor of CYP1A1-mediated B(a)P metabolism,
      prevented all pH(i) changes, and NHE1 activation was blocked by the antioxidant
      thiourea, which inhibited CYP1A1 metabolism-dependent H2O2 production. Regarding
      B(a)P-induced apoptosis, this was prevented by alpha-NF and bongkrekic acid, an
      inhibitor of mitochondria-dependent apoptosis. Interestingly, apoptosis was
      significantly reduced by cariporide. Taken together, our results indicate that
      B(a)P, via H2O2 produced by CYP1A1-dependent metabolism, induces an early
      activation of NHE1, resulting in alkalinization; this appears to play a
      significant role in mitochondria-dependent B(a)P-induced apoptosis.

PMID- 14656998
TI  - Liver fatty acid binding protein is required for high rates of hepatic fatty acid
      oxidation but not for the action of PPARalpha in fasting mice.
AB  - Liver fatty acid binding protein (L-FABP) has been proposed to limit the
      availability of long-chain fatty acids (LCFA) for oxidation and for peroxisome
      proliferator-activated receptor alpha (PPAR-alpha), a fatty acid binding
      transcription factor that determines the capacity of hepatic fatty acid
      oxidation. Here, we used L-FABP null mice to test this hypothesis. Under fasting
      conditions, this mutation reduced beta-hydroxybutyrate (BHB) plasma levels as
      well as BHB release and palmitic acid oxidation by isolated hepatocytes. However,
      the capacity for ketogenesis was not reduced: BHB plasma levels were restored by
      octanoate injection; BHB production and palmitic acid oxidation were normal in
      liver homogenates; and hepatic expression of key PPAR-alpha target (MCAD,
      mitochondrial HMG CoA synthase, ACO, CYP4A3) and other (CPT1, LCAD) genes of
      mitochondrial and extramitochondrial LCFA oxidation and ketogenesis remained at
      wild-type levels. During standard diet, mitochondrial HMG CoA synthase mRNA was
      selectively reduced in L-FABP null liver. These results suggest that under
      fasting conditions, hepatic L-FABP contributes to hepatic LCFA oxidation and
      ketogenesis by a nontranscriptional mechanism, whereas L-FABP can activate
      ketogenic gene expression in fed mice. Thus, the mechanisms whereby L-FABP
      affects fatty acid oxidation may vary with physiological condition.

PMID- 14657000
TI  - S1P3-mediated Akt activation and cross-talk with platelet-derived growth factor
      receptor (PDGFR).
AB  - Akt plays a pivotal role in cell survival and tumorigenesis. We investigated the
      potential interaction between sphingosine-1-phosphate (S1P) and platelet-derived
      growth factor (PDGF) in the Akt signaling pathway. Using mouse embryonic
      fibroblasts (MEFs) from S1P receptor knockout mice, we show here that S1P3 was
      required for S473 phosphorylation of Akt by S1P. In addition, S1P-stimulated
      activation of Akt, but not ERK, was blocked by a PDGF receptor (PDGFR)-specific
      inhibitor, AG1296, suggesting a S1P3-mediated specific crosstalk between the Akt
      signaling pathways of S1P and PDGFR in MEFs. We investigated this crosstalk under
      different conditions and found that both Akt and ERK activation induced by S1P,
      but not lysophosphatidic acid (LPA), in HEY ovarian cancer cells required PDGFR
      but not epidermal growth factor receptor (EGFR) or insulin-like growth factor-I
      receptor (IGFR). Importantly, S1P induced a Gi-dependent tyrosine phosphorylation
      of PDGFR in HEY cells. This dependence on PDGFR in S1P-induced Akt activation was
      also observed in A2780, T47D, and HMEC-1 cells (which express S1P3), but not in
      PC-3 or GI-101A cells (which do not express S1P3), further supporting that S1P3
      mediates the crosstalk between S1P and PDGFR. This is the first report
      demonstrating a unique interaction between S1P3 and PDGFR, in addition to
      demonstrating a specific role for S1P3 in S1P-induced Akt activation.

PMID- 14657001
TI  - Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression
      by interfering with pericyte-mediated endothelial cell survival mechanisms.
AB  - Destruction of existing tumor blood vessels may be achieved by targeting vascular
      endothelial growth factor (VEGF) signaling, which mediates not only endothelial
      cell proliferation but also endothelial cell survival. In this study, however,
      intravital microscopy failed to demonstrate that targeting of VEGFR-2 (by the
      tyrosine kinase inhibitor SU5416) induces significant regression of experimental
      tumor blood vessels. Immunohistochemistry, electron microscopy, expression
      analyses, and in situ hybridization provide evidence that this resistance of
      tumor blood vessels to VEGFR-2 targeting is conferred by pericytes that stabilize
      blood vessels and provide endothelial cell survival signals via the Ang-1/Tie2
      pathway. In contrast, targeting VEGFR-2 plus the platelet-derived growth factor
      receptor (PDGFR)-beta system (PDGFR-beta) signaling (by SU6668) rapidly forced
      40% of tumor blood vessels into regression, rendering these tumors hypoxic as
      shown by phosphorescence quenching. TUNEL staining, electron microscopy, and
      apoptosis blocking experiments suggest that VEGFR-2 plus PDGFR-beta targeting
      enforced tumor blood vessel regression by inducing endothelial cell apoptosis. We
      further show that this is achieved by an interference with pericyte-endothelial
      cell interaction. This study provides novel insights into the mechanisms of how
      1) pericytes may provide escape strategies to anti-angiogenic therapies and 2)
      novel concepts that target not only endothelial cells but also pericyte
      associated pathways involved in vascular stabilization and maturation exert
      potent anti-vascular effects.

PMID- 14657002
TI  - Thymosin beta4 increases hair growth by activation of hair follicle stem cells.
AB  - Thymosin beta4, a 43-amino acid polypeptide that is an important mediator of cell
      migration and differentiation, also promotes angiogenesis and wound healing.
      Here, we report that thymosin beta4 stimulates hair growth in normal rats and
      mice. A specific subset of hair follicular keratinocytes in mouse skin expresses
      thymosin beta4 in a highly coordinated manner during the hair growth cycle. These
      keratinocytes originate in the hair follicle bulge region, a niche for skin stem
      cells. Rat vibrissa follicle clonogenic keratinocytes, closely related, if not
      identical, to the bulge-residing stem cells, were isolated and their migration
      and differentiation increased in the presence of nanomolar concentrations of
      thymosin beta4. Expression and secretion of the extracellular matrix-degrading
      enzyme matrix metalloproteinase-2 were increased by thymosin beta4. Thus,
      thymosin beta4 accelerates hair growth, in part, due to its effect on critical
      events in the active phase of the hair follicle cycle, including promoting the
      migration of stem cells and their immediate progeny to the base of the follicle,
      differentiation, and extracellular matrix remodeling.

PMID- 14657003
TI  - Remyelination of the nonhuman primate spinal cord by transplantation of H
      transferase transgenic adult pig olfactory ensheathing cells.
AB  - Olfactory ensheathing cells (OECs) have been shown to mediate remyelination and
      to stimulate axonal regeneration in a number of in vivo rodent spinal cord
      studies. However, whether OECs display similar properties in the primate model
      has not been tested so far. In the present study, we thus transplanted highly
      purified OECs isolated from transgenic pigs expressing the alpha1,2
      fucosyltransferase gene (H-transferase or HT) gene into a demyelinated lesion of
      the African green monkey spinal cord. Four weeks posttransplantation, robust
      remyelination was found in 62.5% of the lesion sites, whereas there was virtually
      no remyelination in the nontransplanted controls. This together with the
      immunohistochemical demonstration of the grafted cells within the lesioned area
      confirmed that remyelination was indeed achieved by OECs. Additional in vitro
      assays demonstrated 1) that the applied cell suspension consisted of >98% OECs,
      2) that the majority of the cells expressed the transgene, and 3) that expression
      of the HT gene reduced complement activation more than twofold compared with the
      nontransgenic control. This is the first demonstration that xenotransplantation
      of characterized OECs into the primate spinal cord results in remyelination.

PMID- 14657004
TI  - Nitric oxide and reactive oxygen species exert opposing effects on the stability
      of hypoxia-inducible factor-1alpha (HIF-1alpha) in explants of human pial
      arteries.
AB  - Hypoxia induces angiogenesis, partly through stabilization of hypoxia-inducible
      factor-1alpha (HIF-1alpha), leading to transcription of pro-angiogenic factors.
      Here we examined the regulation of HIF-1alpha by hypoxia and nitric oxide (NO) in
      explants of human cerebrovascular smooth muscle cells. Cells were treated with NO
      donors under normoxic or hypoxic (2% O2) conditions, followed by analysis of HIF
      1alpha protein levels. Treatment with the NO donor sodium nitroprusside reduced
      levels of HIF-1alpha, whereas NO donors, NOC-18 and S-nitrosoglutathione,
      increased HIF-1alpha levels. SIN-1, which releases both NO and superoxide (O2*-),
      reduced HIF-1alpha levels, suggesting that inhibitory NO donors may elicit
      effects through peroxynitrite (ONOO*-). O2*- generation by xanthine/xanthine
      oxidase also reduced HIF-1alpha levels, confirming an inhibitory role for
      reactive oxygen species (ROS). Furthermore, superoxide dismutase increased HIF
      1alpha levels, and the NO scavenger carboxy-PTIO reversed HIF-1alpha
      stabilization by NO donors. Effects on HIF-1alpha levels correlated with vascular
      endothelial growth factor transcription but did not affect HIF-1alpha
      transcription, as measured by RT-PCR and luciferase-reporter assays. The results
      indicate that HIF-1alpha is stabilized by agents that produce NO and reduce ROS
      but destabilized by agents that increase ROS, including O2*- and ONOO*-. Thus we
      propose that the effect of NO on HIF-1alpha signaling is critically dependent on
      the form of NO and the physiological environment of the responding cell.

PMID- 14657005
TI  - 25-hydroxyvitamin D3 is an active hormone in human primary prostatic stromal
      cells.
AB  - According to the present paradigm, 1alpha,25-dihydroxyvitamin D3 [1alpha,25
      (OH)2D3] is a biologically active hormone; whereas 25-hydroxyvitamin D3 (25OHD3)
      is regarded as a prohormone activated through the action of 25-hydroxyvitamin D3
      1alpha-hydroxylase (1alpha-hydroxylase). Although the role of vitamin D3 in the
      regulation of growth and differentiation of prostatic epithelial cells has been
      well studied, its action and metabolism in prostatic stroma are still largely
      unknown. We investigated the effects of 25OHD3 and 1alpha,25-(OH)2D3 on two human
      stromal primary cultures termed P29SN and P32S. In a cell proliferation assay,
      25OHD3 was found at physiological concentrations of 100-250 nM to inhibit the
      growth of both primary cultures, whereas 1alpha,25-(OH)2D3 at a pharmacological
      concentration of 10 nM exhibited the growth-inhibitory effects on P29SN cells but
      not on P32S cells. Quantitative real-time RT-PCR analysis revealed that both
      25OHD3 and 1alpha,25-(OH)2D3 induced 25-hydroxyvitamin D3 24-hydroxylase (24
      hydroxylase) mRNA in a dose- and time-dependent manner. By inhibiting 1alpha
      hydroxylase and/or 24-hydroxylase enzyme activities, the induction of 24
      hydroxylase mRNA by 250 nM 25OHD3 was clearly enhanced, suggesting that 1alpha
      hydroxylation is not a prerequisite for the hormonal activity of 25OHD3.
      Altogether our results suggest that 25OHD3 at a high but physiological
      concentration acts as an active hormone with respect to vitamin D3 responsive
      gene regulation and suppression of cell proliferation.

PMID- 14657006
TI  - Allergic humans are hyporesponsive to a CXCR3 ligand-mediated Th1 immunity
      promoting loop.
AB  - CXCR3 binding chemokine CXCL10 (IP-10) markedly enhances antigen-specific Th1
      recall responses in healthy humans, suggesting a role for this pathway in
      maintenance of clinical tolerance to environmental allergens as well as a
      potential therapeutic role for CXCR3 ligands in re-balancing the Th2-dominated
      responses that underlie generation and maintenance of allergic disorders. Here,
      we investigated the capacity of CXCR3 ligands to modulate allergen-driven
      IFNgamma production by healthy and allergic individuals characterized by Th1 and
      Th2 immunity-dominated allergen specific responses, respectively. Exogenous CXCR3
      ligands up-regulated antigen-dependent IFNgamma production from healthy
      individuals' peripheral blood mononuclear cells up to 120-fold, a response
      neutralized by anti-CXCR3 treatment and not emulated by CCR5 ligands. In
      contrast, allergic individuals were strikingly hypo-responsive to CXCR3 ligands
      (P=0.0004). Chemokine-enhanced IFNgamma production correlated with T cell CXCR3
      expression (r=0.736, P=0.0001) in vivo and was independent of Th2 cytokine
      levels. These findings demonstrate that CXCR3-ligation preferentially augments
      ongoing Th1 over Th2 responses and suggest that reduced capacity of allergic
      individuals to respond to CXCR3 ligands promotes the maintenance of human
      allergic disorders.

PMID- 14657007
TI  - Diurnal variation in rat liver thyroid hormone receptor (TR)-alpha messenger
      ribonucleic acid (mRNA) is dependent on the biological clock in the
      suprachiasmatic nucleus, whereas diurnal variation of TR beta 1 mRNA is modified
      by food intake.
AB  - Previous studies have shown a diurnal variation of certain isoforms of thyroid
      hormone receptors (TR) in rat liver. The genesis of these diurnal changes is
      still unknown. To clarify whether the biological clock, located in the
      hypothalamic suprachiasmatic nucleus (SCN), is involved, we made selective SCN
      lesions. Rats with an SCN lesion lost their circadian rhythm of plasma
      corticosterone and TSH when compared with intact animals. TR alpha 1 and TR alpha
      2 mRNA expression of control rats was higher in the light period than in the dark
      period; changes that were abolished in the rats with SCN lesions. In contrast,
      liver TR beta 1 mRNA of intact rats showed a diurnal variation that failed to
      reach statistical significance. To evaluate whether these effects could be
      explained indirectly by the disappearance of rhythmic feeding behavior in rats
      with SCN lesions, we performed a second experiment in which otherwise intact
      animals were subjected to a regular feeding (RF) schedule, with one meal every 4
      h. When compared with rats with free access to food, RF only affected TR beta 1
      mRNA expression and had no effect on the diurnal changes in TR alpha 1 and TR
      alpha 2. We conclude that liver TR beta 1 expression is most clearly affected by
      food intake. Diurnal changes in liver TR alpha 1 and TR alpha 2 are controlled by
      the biological clock in the SCN but not via changes in the daily rhythm of food
      intake. The findings may have physiological relevance for diurnal variation of
      T(3)-dependent gene expression, which is supported by a diurnal variation in the
      expression of the 5'-deiodinase gene.

PMID- 14657008
TI  - Leptin corrects increased gene expression of renal 25-hydroxyvitamin D3-1 alpha
      hydroxylase and -24-hydroxylase in leptin-deficient, ob/ob mice.
AB  - Leptin, the ob gene product secreted by adipocytes, controls overall energy
      balance. We investigated leptin effects on bone metabolism using male leptin
      deficient obese (ob/ob) mice, which had lower bone mineral density (BMD) and
      shorter femurs than lean (?/+) controls. Serum concentrations of calcium,
      phosphate, tartrate-resistant acid phosphatase (a bone resorption marker) and
      alkaline phosphatase, and urinary calcium and phosphate excretion were
      significantly elevated in ob/ob mice, whereas urinary concentrations of
      deoxypyridinoline did not differed between ob/ob and control mice. Because ob/ob
      mice develop severe hypogonadism, testosterone was administered to these mice for
      10 wk (5 mg/kg, sc, twice weekly); this did not affect femoral BMD. Control and
      ob/ob mice showed similar vitamin D-receptor densities in bone and kidney; the
      obese mice had marked increases in serum 1,25-dihydroxyvitamin D(3) [1,25
      (OH)(2)D(3)] and in mRNA expression and activities of renal 25-hydroxyvitamin
      D(3)-1 alpha-hydroxylase (CYP27B1) and -24-hydroxylase (CYP24) compared with
      control mice. Leptin administration to ob/ob mice (4 mg/kg body weight, ip, every
      12 h for 2 d) greatly reduced mRNAs and activities of 1 alpha-hydroxylase and 24
      hydroxylase. Elevated concentrations of serum calcium, phosphate, and 1,25
      (OH)(2)D(3) were normalized by leptin treatment. Thus, leptin suppresses renal
      gene overexpression for 1 alpha-hydroxylase and 24-hydroxylase and corrects
      increased serum concentrations of calcium and phosphate in ob/ob mice. Therefore,
      low BMD in leptin-deficient mice appears to be related to stimulation of bone
      resorption by 1,25-(OH)(2)D(3).

PMID- 14657009
TI  - An ascidian homolog of vertebrate iodothyronine deiodinases.
AB  - In all classes of vertebrates, the deiodination of the prohormone T(4) to T(3)
      represents an essential activation step in thyroid hormone action. The possible
      presence of iodothyronine deiodinase activity in protochordates has been
      demonstrated in vivo. Recent molecular cloning of the genomes and transcripts of
      several ascidian species allows further investigation into thyroid-related
      processes in ascidians. A cDNA clone from Halocynthia roretzi (hrDx) was found to
      have significant homology (30% amino acid identity) with the iodothyronine
      deiodinase gene sequences from vertebrates, including the presence of an in-frame
      UGA codon that might encode a selenocysteine (SeC) in the active site. Because it
      was not certain that the 3' untranslated region (UTR) contained a SeC insertion
      sequence (SECIS) element essential for SeC incorporation, a chimeric expression
      vector of the hrDx coding sequence and the rat deiodinase SECIS element was
      produced, as well as an expression vector containing the intact hrDx cDNA. COS,
      CHO, and HEK cells were transfected with these vectors, and deiodinase activity
      was measured in cell homogenates. Outer-ring deiodinase activity was detected
      using both T(4) and reverse T(3) as substrates, and activity was enhanced by the
      presence of the reductive cofactor dithiothreitol. The enzyme activity was
      optimal during incubation between 20 and 30 C (pH 6-7) and was strongly inhibited
      by gold-thioglucose. The Halocynthia deiodinase appears to be a high Michaelis
      Menten constant (K(m)) enzyme (K(m) reverse T(3), 2 microM; and K(m) T(4), 4
      microM). Deiodinase activity was completely lost upon the substitution of the SeC
      residue in the putative catalytic center by either cysteine or alanine.
      Transfection of the full-length hrDx cDNA produced deiodinase activity confirming
      the presence of a SECIS element in the 3'UTR, as revealed by the SECISearch
      program. In conclusion, our results show, for the first time, the existence of an
      ascidian iodothyronine outer-ring deiodinase. This raises the hypothesis that, in
      protochordates, the prohormone T(4) is activated by enzymatic outer-ring
      deiodination to T(3).

PMID- 14657010
TI  - GLUT9 is differentially expressed and targeted in the preimplantation embryo.
AB  - During preimplantation development in the mouse, it is crucial that glucose
      metabolism not be compromised. Any decrease in glucose uptake at this stage in
      development can compromise the developing embryo. We have cloned another member
      of the glucose transporter family, GLUT9, which is expressed embryonically. Three
      different isoforms were identified. We have shown that two of the mouse GLUT9
      isoforms transport glucose at a rate significantly greater than controls.
      Expression analysis of the preimplantation blastocyst identifies only the
      presence of the shorter GLUT9 isoform, RT-PCR and Western immunoblot confirmed
      this finding. A differential pattern of expression was seen with GLUT9 present at
      the plasma membrane in one- and two-cell zygotes and in an intracellular
      compartment in trophectoderm cells at a blastocyst stage. Although blocking GLUT9
      expression during preimplantation development had no effect on glucose transport
      or apoptosis, transfer of these embryos into pseudopregnant mice resulted in
      increased pregnancy loss, suggesting that GLUT9 is critical for early
      preimplantation development.

PMID- 14657012
TI  - Pregnancy-associated plasma protein a gene expression as a target of inflammatory
      cytokines.
AB  - Pregnancy-associated plasma protein A (PAPP-A) cleaves IGF-binding protein-4
      (IGFBP-4) and appears to enhance local IGF bioavailability in response to injury.
      In this study we determined the effects of growth factors and cytokines involved
      in the healing process on PAPP-A expression in human dermal fibroblasts. There
      was no effect of platelet-derived growth factor, epidermal growth factor, or
      basic fibroblast growth factor on PAPP-A mRNA expression in these cells. However,
      treatment with the proinflammatory cytokines, TNFalpha and IL-1 beta, resulted in
      time- and dose-dependent increases in PAPP-A mRNA and protein expression (3- to 4
      fold maximal effects), which were prevented by actinomycin D. On the other hand,
      interferon-gamma (IFN gamma) treatment markedly inhibited PAPP-A expression.
      IGFBP-4 proteolytic activity was increased 4-fold in medium from TNFalpha- and IL
      1 beta-treated (1 nm) cells and decreased 40% in medium from IFN gamma-treated (1
      nm) cells. IGF-I-stimulated [(3)H]thymidine incorporation was significantly
      enhanced by pretreatment with 1 nm TNFalpha, and this enhancement was blocked in
      the presence of protease-resistant IGFBP-4. In conclusion, PAPP-A expression is
      regulated by inflammatory cytokines in adult human fibroblasts, with functional
      consequences on IGFBP-4 protease activity and IGF-I bioavailability. These data
      provide a mechanism for the regulation of PAPP-A in response to injury and
      further implicate PAPP-A in the wound-healing processes.

PMID- 14657011
TI  - Tyrosine agonists reverse the molecular defects associated with dominant-negative
      mutations in human peroxisome proliferator-activated receptor gamma.
AB  - Loss-of-function mutations in the ligand-binding domain of human peroxisome
      proliferator-activated receptor gamma (PPARgamma) are associated with a novel
      syndrome characterized by partial lipodystrophy and severe insulin resistance.
      Here we have further characterized the properties of natural dominant-negative
      PPARgamma mutants (P467L, V290M) and evaluated the efficacy of putative natural
      ligands and synthetic thiazolidinedione (TZD) or tyrosine-based (TA) receptor
      agonists in rescuing mutant receptor function. A range of natural ligands failed
      to activate the PPARgamma mutants and their transcriptional responses to TZDs
      (e.g. pioglitazone, rosiglitazone) were markedly attenuated, whereas TAs (e.g.
      farglitazar) corrected defects in ligand binding and coactivator recruitment by
      the PPARgamma mutants, restoring transcriptional function comparable with wild
      type receptor. Transcriptional silencing via recruitment of corepressor
      contributes to dominant-negative inhibition of wild type by the P467L and V290M
      mutants and the introduction of an artificial mutation (L318A) disrupting
      corepressor interaction abrogated their dominant-negative activity. More complete
      ligand-dependent corepressor release and reversal of dominant-negative inhibition
      was achieved with TA than TZD agonists. Modeling suggests a structural basis for
      these observations: both mutations destabilize helix 12 to favor receptor
      corepressor interaction; conversely, farglitazar makes more extensive contacts
      than rosiglitazone within the ligand-binding pocket, to stabilize helix 12,
      facilitating corepressor release and transcriptional activation. Farglitazar was
      a more potent inducer of PPARgamma target gene (aP2) expression in peripheral
      blood mononuclear cells with the P467L mutation. Having shown that rosiglitazone
      is of variable and limited efficacy in these subjects, we suggest that TAs may
      represent a more rational therapeutic approach.

PMID- 14657013
TI  - BIG-3, a novel WD-40 repeat protein, is expressed in the developing growth plate
      and accelerates chondrocyte differentiation in vitro.
AB  - Among the local signaling pathways that regulate the sequential steps of
      chondrocyte differentiation is the bone morphogenetic protein (BMP) signaling
      pathway. We have identified a novel gene, named BIG-3 (BMP-2-induced gene 3 kb)
      that is expressed in a BMP-regulated fashion in the prechondroblastic cell line
      MLB13MYC clone 17. BIG-3 is also expressed in proliferating and hypertrophic
      chondrocytes in the developing growth plate in vivo. We undertook studies to
      address whether BIG-3 played a functional role in chondrocyte differentiation,
      using mouse clonal chondrogenic ATDC5 cells. BIG-3 protein levels increased
      during ITS (insulin, transferrin, sodium selenite)-induced ATDC5 differentiation
      and in response to BMP-2 treatment. To determine whether stable expression of BIG
      3 could alter the program of chondrocytic differentiation, ATDC5 cells were
      stably transfected with the full-length coding region of BIG-3 (ATDC5-BIG-3) or
      with the empty vector (ATDC5-EV). Accelerated matrix proteoglycan synthesis was
      observed in the pooled ATDC5-BIG-3 clones. Alkaline phosphatase and osteopontin
      mRNA levels were also increased in ATDC5-BIG-3 clones compared with ATDC5-EV
      clones. Stable expression of BIG-3 also accelerated mineralized matrix formation
      in both the presence and absence of ITS. These findings, which demonstrate that
      BIG-3 accelerates chondrocyte differentiation in vitro, combined with the
      observation that BIG-3 is expressed in the growth plate during embryonic
      development, suggest that this novel protein is likely to play an in vivo
      regulatory role in the developing growth plate.

PMID- 14657014
TI  - Cochlin, a secreted von Willebrand factor type a domain-containing factor, is
      regulated by leukemia inhibitory factor in the uterus at the time of embryo
      implantation.
AB  - Embryo implantation is a required step in the reproduction of all mammals. In
      mice, a transient rise in the uterine expression of leukemia inhibitory factor
      (LIF) occurs on d 4 of pregnancy and is essential for embryo implantation.
      However, which genes are regulated by LIF in the uterus at implantation has not
      been determined. We performed a subtractive hybridization assay between luminal
      epithelial (LE) mRNAs from d 3 and 4 of pregnancy to find genes up-regulated on d
      4 and which would be potentially regulated by LIF. One candidate, Coch-5b2, was
      up-regulated on the day of implantation. Coch mRNA localized to the LE of wild
      type mice and was not detected in uteri from Lif-deficient mice. Treatment of LE
      with LIF, both in vitro and in vivo, resulted in the up-regulation of Coch. Coch
      is also highly expressed in other tissues, including the spleen and inner ear,
      but only in the uterus is Coch expression regulated by LIF. Mice were derived in
      which Coch was either deleted or tagged with a LacZ reporter. In mice carrying
      the tagged Coch gene, expression of Coch was detected in the LE and also at the
      site of embryo implantation. However, mice in which the Coch gene was deleted
      were normal, showing no overt defects in their reproduction. Although loss of
      Coch expression is not essential to reproduction in mice, it may serve as a
      useful marker for assessing the state of uterine receptivity in response to LIF
      at the onset of implantation.

PMID- 14657015
TI  - Protein kinase A regulates AKAP250 (gravin) scaffold binding to the beta2
      adrenergic receptor.
AB  - A-kinase-anchoring protein 250 (AKAP250; gravin) acts as a scaffold that binds
      protein kinase A (PKA), protein kinase C and protein phosphatases, associating
      reversibly with the beta(2)-adrenergic receptor. The receptor-binding domain of
      the scaffold and the regulation of the receptor-scaffold association was revealed
      through mutagenesis and biochemical analyses. The AKAP domain found in other
      members of this superfamily is essential for the scaffold-receptor interactions.
      Gravin constructs lacking the AKAP domain displayed no binding to the receptor.
      Metabolic labeling studies in vivo demonstrate agonist-stimulated phosphorylation
      of gravin and enhanced gravin-receptor association. Analysis of the AKAP domain
      revealed two canonical PKA sites phosphorylated in response to elevated cAMP,
      blocked by PKA inhibitor, and essential for scaffold-receptor association and for
      resensitization of the receptor. The AKAP appears to provide the catalytic PKA
      activity responsible for phosphorylation of the scaffold in response to agonist
      activation of the receptor as well as for the association of the scaffold with
      the receptor, a step critical to receptor resensitization.

PMID- 14657016
TI  - The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated
      by sortilin.
AB  - Most soluble lysosomal proteins bind the mannose 6-phosphate receptor (M6P-R) to
      be sorted to the lysosomes. However, the lysosomes of I-cell disease (ICD)
      patients, a condition resulting from a mutation in the phosphotransferase that
      adds mannose 6-phosphate to hydrolases, have near normal levels of several
      lysosomal proteins, including the sphingolipid activator proteins (SAPs), GM2AP
      and prosaposin. We tested the hypothesis that SAPs are targeted to the lysosomal
      compartment via the sortilin receptor. To test this hypothesis, a dominant
      negative construct of sortilin and a sortilin small interfering RNA (siRNA) were
      introduced into COS-7 cells. Our results showed that both the truncated sortilin
      and the sortilin siRNA block the traffic of GM2AP and prosaposin to the lysosomal
      compartment. This observation was confirmed by a co-immunoprecipitation, which
      demonstrated that GM2AP and prosaposin are interactive partners of sortilin.
      Furthermore, a dominant-negative mutant GGA prevented the trafficking of
      prosaposin and GM2AP to lysosomes. In conclusion, our results show that the
      trafficking of SAPs is dependent on sortilin, demonstrating a novel lysosomal
      trafficking.

PMID- 14657017
TI  - Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C
      terminal region of Oxa1.
AB  - The yeast mitochondrial Oxa1 protein is a member of the conserved Oxa1/YidC/Alb3
      protein family involved in the membrane insertion of proteins. Oxa1 mediates the
      insertion of proteins (nuclearly and mitochondrially encoded) into the inner
      membrane. The mitochondrially encoded substrates interact directly with Oxa1
      during their synthesis as nascent chains and in a manner that is supported by the
      associated ribosome. We have investigated if the Oxa1 complex interacts with the
      mitochondrial ribosome. Evidence to support a physical association between Oxa1
      and the large ribosomal subunit is presented. Our data indicate that the matrix
      exposed C-terminal region of Oxa1 plays an important role supporting the
      ribosomal-Oxa1 interaction. Truncation of this C-terminal segment compromises the
      ability of Oxa1 to support insertion of substrate proteins into the inner
      membrane. Oxa1 can be cross-linked to Mrp20, a component of the large ribosomal
      subunit. Mrp20 is homologous to L23, a subunit located next to the peptide exit
      tunnel of the ribosome. We propose that the interaction of Oxa1 with the ribosome
      serves to enhance a coupling of translation and membrane insertion events.

PMID- 14657018
TI  - Ribosome binding to the Oxa1 complex facilitates co-translational protein
      insertion in mitochondria.
AB  - The Oxa1 translocase of the mitochondrial inner membrane facilitates the
      insertion of both mitochondrially and nuclear-encoded proteins from the matrix
      into the inner membrane. Most mitochondrially encoded proteins are hydrophobic
      membrane proteins which are integrated into the lipid bilayer during their
      synthesis on mitochondrial ribosomes. The molecular mechanism of this co
      translational insertion process is unknown. Here we show that the matrix-exposed
      C-terminus of Oxa1 forms an alpha-helical domain that has the ability to bind to
      mitochondrial ribosomes. Deletion of this Oxa1 domain strongly diminished the
      efficiency of membrane insertion of subunit 2 of cytochrome oxidase, a
      mitochondrially encoded substrate of the Oxa1 translocase. This suggests that co
      translational membrane insertion of mitochondrial translation products is
      facilitated by a physical interaction of translation complexes with the membrane
      bound translocase.

PMID- 14657019
TI  - Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7.
AB  - Arkadia was originally identified as a protein that enhances signalling activity
      of Nodal and induces mammalian nodes during early embryogenesis; however, the
      mechanisms by which Arkadia affects transforming growth factor-beta (TGF-beta)
      superfamily signalling have not been determined. Here we show that Arkadia is
      widely expressed in mammalian tissues, and that it enhances both TGF-beta and
      bone morphogenetic protein (BMP) signalling. Arkadia physically interacts with
      inhibitory Smad, Smad7, and induces its poly-ubiquitination and degradation. In
      contrast to Smurf1, which interacts with TGF-beta receptor complexes through
      Smad7 and degrades them, Arkadia fails to associate with TGF-beta receptors. In
      contrast to Smad7, expression of Arkadia is down-regulated by TGF-beta. Silencing
      of the Arkadia gene resulted in repression of transcriptional activities induced
      by TGF-beta and BMP, and accumulation of the Smad7 protein. Arkadia may thus play
      an important role as an amplifier of TGF-beta superfamily signalling under both
      physiological and pathological conditions.

PMID- 14657020
TI  - A novel angiotensin II type 2 receptor signaling pathway: possible role in
      cardiac hypertrophy.
AB  - We describe a novel signaling mechanism mediated by the G-protein-coupled
      receptor (GPCR) angiotensin II (Ang II) type 2 receptor (AT(2)). Yeast two-hybrid
      studies and affinity column binding assay show that the isolated AT(2) C-terminus
      binds to the transcription factor promyelocytic zinc finger protein (PLZF).
      Cellular studies employing confocal microscopy show that Ang II stimulation
      induces cytosolic PLZF to co-localize with AT(2) at the plasma membrane, then
      drives AT(2) and PLZF to internalize. PLZF slowly emerges in the nucleus whereas
      AT(2) accumulates in the perinuclear region. Nuclear PLZF binds to a consensus
      sequence of the phosphatidylinositol-3 kinase p85 alpha subunit (p85 alpha PI3K)
      gene. AT(2) enhances expression of p85 alpha PI3K followed by enhanced p70(S6)
      kinase, essential to protein synthesis. An inactive mutant of PLZF abolishes this
      effect. PLZF is expressed robustly in the heart in contrast to many other
      tissues. This cardiac selective pathway involving AT(2), PLZF and p85 alpha PI3K
      may explain the absence of a cardiac hypertrophic response in AT(2) gene-deleted
      mice.

PMID- 14657021
TI  - Discontinuous movement and conformational change during pausing and termination
      by T7 RNA polymerase.
AB  - Time-resolved characterization of T7 RNA polymerase pausing and terminating at a
      class II termination site has been carried out using site-specifically tethered
      chemical nucleases. The data indicate that T7RNAP normally moves uniformly down
      the template as a rigid body. However, at the class II site this movement is
      interrupted, and the leading edge of the polymerase moves further along the DNA
      than the trailing edge. This discontinuous movement may persist until it can no
      longer be accommodated by conformational changes in the elongation complex, at
      which point the polymerase can either pause or terminate. Termination, but not
      pausing, is abrogated by introduction of a disulfide bond between the polymerase
      fingers and thumb subdomains. The introduced cysteines disrupt a thumb-fingers
      salt-bridge and, under reducing conditions, this mutant enzyme shows reduced
      processivity coincident with extension of the RNA to 5 nt. These observations
      suggest that termination requires that the thumb and fingers subdomains move
      apart, in a reversal of a conformational change important for initially forming a
      stable transcription complex.

PMID- 14657022
TI  - A novel docking site on Mediator is critical for activation by VP16 in mammalian
      cells.
AB  - ARC92/ACID1 was identified as a novel specific target of the herpes simplex
      transactivator VP16 using an affinity purification procedure. Characterization of
      the protein revealed tight interactions with human Mediator mediated through a
      von Willebrand type A domain. ARC92/ACID1 further contains a novel activator
      interacting domain (ACID), which it shares with at least one other human gene
      termed PTOV1/ACID2. The structure of ARC92/ACID1 is of ancient origin but is
      conserved in mammals and in selected higher eukaryotes. A subpopulation of
      Mediator is associated with ARC92/ACID1, which is specifically required for VP16
      activation both in vitro and in mammalian cells, but is dispensable for other
      activators such as SP1. Despite many known targets of VP16, ARC92/ACID1 appears
      to impose a critical control on transcription activation by VP16 in mammalian
      cells.

PMID- 14657023
TI  - Growth inhibition by the mammalian SWI-SNF subunit Brm is regulated by
      acetylation.
AB  - In mammalian cells, the SWI-SNF chromatin-remodeling complex is a regulator of
      cell proliferation, and overexpression of the catalytic subunit Brm interferes
      with cell cycle progression. Here, we show that treatment with histone
      deacetylase (HDAC) inhibitors reduces the inhibitory effect of Brm on the growth
      of mouse fibroblasts. This observation led to the identification of two carboxy
      terminal acetylation sites in the Brm protein. Mutation of these sites into non
      acetylatable sequences increased both the growth-inhibitory and the
      transcriptional activities of Brm. We also show that culture in the presence of
      HDAC inhibitors facilitates the isolation of clones overexpressing Brm. Removal
      of the HDAC inhibitors from the growth medium of these clones leads to
      downregulation of cyclin D1. This downregulation is absent in cell transformed by
      oncogenic ras.

PMID- 14657024
TI  - Cooperation between the GATA and RUNX factors Serpent and Lozenge during
      Drosophila hematopoiesis.
AB  - Members of the GATA and RUNX families of genes appear to have conserved functions
      during hematopoiesis from Drosophila to mammals. In Drosophila, the GATA factor
      Serpent (Srp) is required in blood cell progenitors for the formation of the two
      populations of blood cells (plasmatocytes and crystal cells), while the RUNX
      factor Lozenge (Lz) is specifically required for crystal cell development. Here
      we investigate the function and the mechanisms of action of Lz during
      hematopoiesis. Our results indicate that Lz can trigger crystal cell development.
      Interestingly, we show that Lz function is strictly dependent on the presence of
      functional Srp and that Srp and Lz cooperate to induce crystal cell
      differentiation in vivo. Furthermore, we show that Srp and Lz directly interact
      in vitro and that this interaction is conserved between Drosophila and mammals.
      Moreover, both Srp and mouse GATA1 synergize with mouse RUNX1 to activate
      transcription. We propose that interaction and cooperation between GATA and RUNX
      factors may play an important role in regulating blood cell formation from
      Drosophila to mammals.

PMID- 14657025
TI  - Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan
      steroid receptor.
AB  - Nur77 is a nuclear orphan steroid receptor that has been implicated in negative
      selection. Expression of Nur77 in thymocytes and cell lines leads to apoptosis
      through a mechanism that remains unclear. In some cell lines, Nur77 was reported
      to act through a transcription-independent mechanism involving translocation to
      mitochondria, leading to cytochrome c release. However, we show here that Nur77
      mediated apoptosis in thymocytes does not involve cytoplasmic cytochrome c
      release and cannot be rescued by Bcl-2. Microarray analysis shows that Nur77
      induces many genes, including two novel genes (NDG1, NDG2) and known apoptotic
      genes FasL and TRAIL. Characterization of NDG1 and NDG2 indicates that NDG1
      initiates a novel apoptotic pathway in a Bcl-2-independent manner. Thus Nur77
      mediated apoptosis in T cells involves Bcl-2 independent transcriptional
      activation of several known and novel apoptotic pathways.

PMID- 14657026
TI  - Critical loss of CBP/p300 histone acetylase activity by caspase-6 during
      neurodegeneration.
AB  - By altering chromatin structure, histone acetyltransferases (HATs) act as
      transcriptional regulators. We observed in a model of primary neurons that
      histone acetylation levels decreased at the onset of apoptosis. The CREB-binding
      protein (CBP) is a HAT of particular interest because it also acts as a co
      activator controlling, among others, CREB-dependent transcriptional activity. It
      has been demonstrated that CREB exerts neuroprotective functions, but the fate of
      CBP during neuronal apoptosis remained unclear till now. This work provided
      evidence that CBP is specifically targeted by caspases and calpains at the onset
      of neuronal apoptosis, and CBP was futher identified as a new caspase-6
      substrate. This ultimately impinged on the CBP/p300 HAT activity that decreased
      with time during apoptosis entry, whereas total cellular HAT activity remained
      unchanged. Interestingly, CBP loss and histone deacetylation were observed in two
      different pathological contexts: amyloid precursor protein-dependent signaling
      and amyotrophic lateral sclerosis model mice, indicating that these modifications
      are likely to contribute to neurodegenerative diseases. In terms of function, we
      demonstrated that fine-tuning of CBP HAT activity is necessary to ensure
      neuroprotection.

PMID- 14657027
TI  - Regulation of HIV-1 gene expression by histone acetylation and factor recruitment
      at the LTR promoter.
AB  - In HIV-1 infected cells, the LTR promoter, once organized into chromatin, is
      transcriptionally inactive in the absence of stimulation. To examine the
      chromosomal events involved in transcriptional activation, we analyzed histone
      acetylation and factor recruitment at contiguous LTR regions by a quantitative
      chromatin immunoprecipitation assay. In chronically infected cells treated with a
      phorbol ester, we found that acetylation of both histones H3 and H4 occurs at
      discrete nucleosomal regions before the onset of viral mRNA transcription.
      Concomitantly, we observed the recruitment of known cellular acetyl-transferases
      to the promoter, including CBP, P/CAF and GCN5, as well as that of the p65
      subunit of NF-kappa B. The specific contribution of the viral Tat transactivator
      was assayed in cells harboring the sole LTR. We again observed nucleosomal
      acetylation and the recruitment of specific co-factors to the viral LTR upon
      activation by either recombinant Tat or a phorbol ester. Strikingly, P/CAF was
      found associated with the promoter only in response to Tat. Taken together, these
      results contribute to the elucidation of the molecular events underlying HIV-1
      transcriptional activation.

PMID- 14657028
TI  - A La protein requirement for efficient pre-tRNA folding.
AB  - The La protein protects the 3' ends of many nascent small RNAs from exonucleases.
      Here we report that La is required for efficient folding of certain pre-tRNAs. A
      mutation in pre-tRNA(Arg)(CCG) causes yeast cells to be cold-sensitive and to
      require the La protein Lhp1p for efficient growth. When the mutant cells are
      grown at low temperature, or when Lhp1p is depleted, mature tRNA(Arg)(CCG) is not
      efficiently aminoacylated. The mutation causes the anticodon stem of pre
      tRNA(Arg)(CCG) to misfold into an alternative helix in vitro. Intragenic
      suppressor mutations that disrupt the misfolded helix or strengthen the correct
      helix alleviate the requirement for Lhp1p, providing evidence that the anticodon
      stem misfolds in vivo. Chemical and enzymatic footprinting experiments suggest a
      model in which Lhp1p stabilizes the correctly folded stem. Lhp1p is also required
      for efficient aminoacylation of two wild-type tRNAs when yeast are grown at low
      temperature. These experiments reveal that pre-tRNAs can require protein
      assistance for efficient folding in vivo.

PMID- 14657029
TI  - Yeast Nop15p is an RNA-binding protein required for pre-rRNA processing and
      cytokinesis.
AB  - Nop15p is an essential protein that contains an RNA recognition motif (RRM) and
      localizes to the nucleoplasm and nucleolus. Cells depleted of Nop15p failed to
      synthesize the 25S and 5.8S rRNA components of the 60S ribosomal subunit, and
      exonucleolytic 5' processing of 5.8S rRNA was strongly inhibited. Pre-rRNAs co
      precipitated with tagged Nop15p confirmed its association with early pre-60S
      particles and Nop15p bound a pre-rRNA transcript in vitro. Nop15p-depleted cells
      show an unusually abrupt growth arrest prior to substantial depletion of
      ribosomal subunits. Following cell synchronization in mitosis, Nop15p-depleted
      cells undergo nuclear division with wild-type kinetics, activate the mitotic exit
      network and disassemble their mitotic spindle. However, they uniformly arrest at
      cytokinesis and fail to assemble a contractile actin ring at the bud neck. In
      dividing wild-type cells, segregation of nucleolar proteins to the daughter
      nuclei occurs after separation of the nucleoplasm. In these late mitotic cells,
      Nop15p was partially delocalized from the nucleolus to the nucleoplasm,
      consistent with a specific function in cell division in addition to its role in
      ribosome synthesis.

PMID- 14657030
TI  - Nsl1p is essential for the establishment of bipolarity and the localization of
      the Dam-Duo complex.
AB  - We identified a physical complex consisting of Mtw1p, an established kinetochore
      protein, with Nnf1p, Nsl1p and Dsn1p and have demonstrated that Nnf1p, Nsl1p and
      Dsn1p localize to the Saccharomyces cerevisiae kinetochore. When challenged prior
      to metaphase, the temperature-sensitive mutants nsl1-16 and nsl1-42 as well as
      Nsl1p-depleted cells failed to establish a bipolar spindle-kinetochore
      interaction and executed monopolar segregation of sister chromatids. In contrast,
      an nsl1-16 defect could not be evoked after the establishment of bipolarity. The
      observed phenotype is characteristic of that of mutants with defects in the
      protein kinase Ipl1p or components of the Dam-Duo kinetochore complex. However
      nsl1 mutants did not exhibit a defect in microtubule-kinetochore untethering as
      the ipl1-321 mutant does. Instead, they exhibited a severe defect in the
      kinetochore localization of the Dam-Duo complex suggesting this to be the cause
      for the failure of nsl1 cells to establish bipolarity. Moreover the analysis of
      Nsl1p-depleted cells indicated that Nsl1p is required for the spindle checkpoint
      and kinetochore integrity.

PMID- 14657031
TI  - Mitotic regulation of the human anaphase-promoting complex by phosphorylation.
AB  - The anaphase-promoting complex (APC) or cyclosome is a ubiquitin ligase that
      initiates anaphase and mitotic exit. APC activation is thought to depend on APC
      phosphorylation and Cdc20 binding. We have identified 43 phospho-sites on APC of
      which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts
      of Apc1 and the tetratricopeptide repeat (TPR) subunits Cdc27, Cdc16, Cdc23 and
      Apc7. In vitro, at least 15 of the mitotic phospho-sites can be generated by
      cyclin-dependent kinase 1 (Cdk1), and 3 by Polo-like kinase 1 (Plk1). APC
      phosphorylation by Cdk1, but not by Plk1, is sufficient for increased Cdc20
      binding and APC activation. Immunofluorescence microscopy using phospho
      antibodies indicates that APC phosphorylation is initiated in prophase during
      nuclear uptake of cyclin B1. In prometaphase phospho-APC accumulates on
      centrosomes where cyclin B ubiquitination is initiated, appears throughout the
      cytosol and disappears during mitotic exit. Plk1 depletion neither prevents APC
      phosphorylation nor cyclin A destruction in vivo. These observations imply that
      APC activation is initiated by Cdk1 already in the nuclei of late prophase cells.

PMID- 14657032
TI  - The Mre11 complex is required for ATM activation and the G2/M checkpoint.
AB  - The maintenance of genome integrity requires a rapid and specific response to
      many types of DNA damage. The conserved and related PI3-like protein kinases,
      ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate
      signal transduction pathways in response to genomic insults, such as DNA double
      strand breaks (DSBs). It is unclear which proteins recognize DSBs and activate
      these pathways, but the Mre11/Rad50/NBS1 complex has been suggested to act as a
      damage sensor. Here we show that infection with an adenovirus lacking the E4
      region also induces a cellular DNA damage response, with activation of ATM and
      ATR. Wild-type virus blocks this signaling through degradation of the Mre11
      complex by the viral E1b55K/E4orf6 proteins. Using these viral proteins, we show
      that the Mre11 complex is required for both ATM activation and the ATM-dependent
      G(2)/M checkpoint in response to DSBs. These results demonstrate that the Mre11
      complex can function as a damage sensor upstream of ATM/ATR signaling in
      mammalian cells.

PMID- 14657033
TI  - Mouse Rev1 protein interacts with multiple DNA polymerases involved in
      translesion DNA synthesis.
AB  - Pol kappa and Rev1 are members of the Y family of DNA polymerases involved in
      tolerance to DNA damage by replicative bypass [translesion DNA synthesis (TLS)].
      We demonstrate that mouse Rev1 protein physically associates with Pol kappa. We
      show too that Rev1 interacts independently with Rev7 (a subunit of a TLS
      polymerase, Pol zeta) and with two other Y-family polymerases, Pol iota and Pol
      eta. Mouse Pol kappa, Rev7, Pol iota and Pol eta each bind to the same
      approximately 100 amino acid C-terminal region of Rev1. Furthermore, Rev7
      competes directly with Pol kappa for binding to the Rev1 C-terminus.
      Notwithstanding the physical interaction between Rev1 and Pol kappa, the DNA
      polymerase activity of each measured by primer extension in vitro is unaffected
      by the complex, either when extending normal primer-termini, when bypassing a
      single thymine glycol lesion, or when extending certain mismatched primer
      termini. Our observations suggest that Rev1 plays a role(s) in mediating protein
      protein interactions among DNA polymerases required for TLS. The precise
      function(s) of these interactions during TLS remains to be determined.

PMID- 14657034
TI  - Visualizing telomere dynamics in living mammalian cells using PNA probes.
AB  - Chromosome ends are protected from degradation by the presence of the highly
      repetitive hexanucleotide sequence of TTAGGG and associated proteins. These so
      called telomeric complexes are suggested to play an important role in
      establishing a functional nuclear chromatin organization. Using peptide nucleic
      acid (PNA) probes, we studied the dynamic behavior of telomeric DNA repeats in
      living human osteosarcoma U2OS cells. A fluorescent cy3-labeled PNA probe was
      introduced in living cells by glass bead loading and was shown to specifically
      associate with telomeric DNA shortly afterwards. Telomere dynamics were imaged
      for several hours using digital fluorescence microscopy. While the majority of
      telomeres revealed constrained diffusive movement, individual telomeres in a
      human cell nucleus showed significant directional movements. Also, a subfraction
      of telomeres were shown to associate and dissociate, suggesting that in vivo
      telomere clusters are not stable but dynamic structures. Furthermore, telomeres
      were shown to associate with promyelocytic leukemia (PML) bodies in a dynamic
      manner.

PMID- 14657035
TI  - IAP-antagonists exhibit non-redundant modes of action through differential DIAP1
      binding.
AB  - The Drosophila inhibitor of apoptosis protein DIAP1 ensures cell viability by
      directly inhibiting caspases. In cells destined to die this IAP-mediated
      inhibition of caspases is overcome by IAP-antagonists. Genetic evidence indicates
      that IAP-antagonists are non-equivalent and function synergistically to promote
      apoptosis. Here we provide biochemical evidence for the non-equivalent mode of
      action of Reaper, Grim, Hid and Jafrac2. We find that these IAP-antagonists
      display differential and selective binding to specific DIAP1 BIR domains.
      Consistently, we show that each DIAP1 BIR region associates with distinct
      caspases. The differential DIAP1 BIR interaction seen both between initiator and
      effector caspases and within IAP-antagonist family members suggests that
      different IAP-antagonists inhibit distinct caspases from interacting with DIAP1.
      Surprisingly, we also find that the caspase-binding residues of XIAP predicted to
      be strictly conserved in caspase-binding IAPs, are absent in DIAP1. In contrast
      to XIAP, residues C-terminal to the DIAP1 BIR1 domain are indispensable for
      caspase association. Our studies on DIAP1 and caspases expose significant
      differences between DIAP1 and XIAP suggesting that DIAP1 and XIAP inhibit
      caspases in different ways.

PMID- 14657036
TI  - Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl
      2 family member Bim.
AB  - Osteoclasts (OCs) undergo rapid apoptosis without trophic factors, such as
      macrophage colony-stimulating factor (M-CSF). Their apoptosis was associated with
      a rapid and sustained increase in the pro-apoptotic BH3-only Bcl-2 family member
      Bim. This was caused by the reduced ubiquitylation and proteasomal degradation of
      Bim that is mediated by c-Cbl. Although the number of OCs was increased in the
      skeletal tissues of bim-/- mice, the mice exhibited mild osteosclerosis due to
      reduced bone resorption. OCs differentiated from bone marrow cells of bim-/-
      animals showed a marked prolongation of survival in the absence of M-CSF,
      compared with bim+/+ OCs, but the bone-resorbing activity of bim-/- OCs was
      significantly reduced. Overexpression of a degradation-resistant lysine-free Bim
      mutant in bim-/- cells abrogated the anti-apoptotic effect of M-CSF, while wild
      type Bim did not. These results demonstrate that ubiquitylation-dependent
      regulation of Bim levels is critical for controlling apoptosis and activation of
      OCs.

PMID- 14657038
TI  - Influence of L-NAME on pulmonary O2 uptake kinetics during heavy-intensity cycle
      exercise.
AB  - We hypothesized that inhibition of nitric oxide synthase (NOS) by N(G)-nitro-L
      arginine methyl ester (L-NAME) would alleviate the inhibition of mitochondrial
      oxygen uptake (Vo(2)) by nitric oxide and result in a speeding of phase II
      pulmonary Vo(2) kinetics at the onset of heavy-intensity exercise. Seven men
      performed square-wave transitions from unloaded cycling to a work rate requiring
      40% of the difference between the gas exchange threshold and peak Vo(2) with and
      without prior intravenous infusion of L-NAME (4 mg/kg in 50 ml saline over 60
      min). Pulmonary gas exchange was measured breath by breath, and Vo(2) kinetics
      were determined from the averaged response to two exercise bouts performed in
      each condition. There were no significant differences between the control (C) and
      L-NAME conditions (L) for baseline Vo(2), the duration of phase I, or the
      amplitude of the primary Vo(2) response. However, the time constant of the Vo(2)
      response in phase II was significantly smaller (mean +/- SE: C: 25.1 +/- 3.0 s;
      L: 21.8 +/- 3.3 s; P < 0.05), and the amplitude of the Vo(2) slow component was
      significantly greater (C: 240 +/- 47 ml/min; L: 363 +/- 24 ml/min; P < 0.05)
      after L-NAME infusion. These data indicate that inhibition of NOS by L-NAME
      results in a significant (13%) speeding of Vo(2) kinetics and a significant
      increase in the amplitude of the Vo(2) slow component in the transition to heavy
      intensity cycle exercise in men. The speeding of the primary component Vo(2)
      kinetics after L-NAME infusion indicates that at least part of the intrinsic
      inertia to oxidative metabolism at the onset of heavy-intensity exercise may
      result from inhibition of mitochondrial Vo(2) by nitric oxide. The cause of the
      larger Vo(2) slow-component amplitude with L-NAME requires further investigation
      but may be related to differences in muscle blood flow early in the rest-to
      exercise transition.

PMID- 14657037
TI  - The crucial role of caspase-9 in the disease progression of a transgenic ALS
      mouse model.
AB  - Mutant copper/zinc superoxide dismutase (SOD1)-overexpressing transgenic mice, a
      mouse model for familial amyotrophic lateral sclerosis (ALS), provides an
      excellent resource for developing novel therapies for ALS. Several observations
      suggest that mitochondria-dependent apoptotic signaling, including caspase-9
      activation, may play an important role in mutant SOD1-related neurodegeneration.
      To elucidate the role of caspase-9 in ALS, we examined the effects of an
      inhibitor of X chromosome-linked inhibitor of apoptosis (XIAP), a mammalian
      inhibitor of caspase-3, -7 and -9, and p35, a baculoviral broad caspase inhibitor
      that does not inhibit caspase-9. When expressed in spinal motor neurons of mutant
      SOD1 mice using transgenic techniques, XIAP attenuated disease progression
      without delaying onset. In contrast, p35 delayed onset without slowing disease
      progression. Moreover, caspase-9 was activated in spinal motor neurons of human
      ALS subjects. These data strongly suggest that caspase-9 plays a crucial role in
      disease progression of ALS and constitutes a promising therapeutic target.

PMID- 14657039
TI  - Postexercise protein supplementation improves health and muscle soreness during
      basic military training in Marine recruits.
AB  - Elevated postexercise amino acid availability has been demonstrated to enhance
      muscle protein synthesis acutely, but the long-term impact of postexercise
      protein supplementation on variables such as health, muscle soreness, and
      function are unclear. Healthy male US Marine recruits from six platoons (US
      Marine Corps Base, Parris Island, SC; n = 387; 18.9 +/- 0.1 yr, 74.7 +/- 1.1 kg,
      13.8 +/- 0.4% body fat) were randomly assigned to three treatments within each
      platoon. Nutrients supplemented immediately postexercise during the 54-day basic
      training were either placebo (0 g carbohydrate, 0 g protein, 0 g fat), control
      (8, 0, 3), or protein supplement (8, 10, 3). Subjects and observers making
      measurements and data analysis were blinded to subject groupings. Compared with
      placebo and control groups, the protein-supplemented group had an average of 33%
      fewer total medical visits, 28% fewer visits due to bacterial/viral infections,
      37% fewer visits due to muscle/joint problems, and 83% fewer visits due to heat
      exhaustion. Recruits experiencing heat exhaustion had greater body mass, lean,
      fat, and water losses. Muscle soreness immediately postexercise was reduced by
      protein supplementation vs. placebo and control groups on both days 34 and 54.
      Postexercise protein supplementation may not only enhance muscle protein
      deposition but it also has significant potential to positively impact health,
      muscle soreness, and tissue hydration during prolonged intense exercise training,
      suggesting a potential therapeutic approach for the prevention of health problems
      in severely stressed exercising populations.

PMID- 14657041
TI  - Facilitation of dopamine and acetylcholine release by intermittent hypoxia in
      PC12 cells: involvement of calcium and reactive oxygen species.
AB  - We have investigated the effects of preconditioning pheochromocytoma (PC12) cells
      with intermittent hypoxia (IH) on transmitter release during acute hypoxia. Cell
      cultures were exposed to either alternating cycles of hypoxia (1% O(2) + 5%
      CO(2); 30 s/cycle) and normoxia (21% O(2) + 5% CO(2); 3 min/cycle) for 15 or 60
      cycles or normoxia alone (control) for similar durations. Control and IH cells
      were challenged with either hyperoxia (basal release) or acute hypoxia (Po(2) of
      approximately 35 Torr) for 5 min, and the amounts of dopamine (DA) and
      acetylcholine (ACh) released in the medium were determined by HPLC combined with
      electrochemical detection. Hypoxia augmented DA (approximately 80%) but not ACh
      release in naive cells, whereas, in IH-conditioned cells, it further enhanced DA
      release (ranging from 120 to approximately 145%) and facilitated ACh release
      (approximately 30%). Hypoxia-evoked augmentation of transmitter release was not
      seen in cells conditioned with sustained hypoxia. IH-induced increase in DA but
      not IH-induced ACh release during hypoxia was partially inhibited by cadmium
      chloride (100 microM), a voltage-gated Ca(2+) channel blocker. By contrast, 2
      aminoethoxydiphenylborate (75 microM), a blocker of inositol 1,4,5-trisphosphate
      (IP(3)) receptors, and N-acetyl-L-cysteine (300 microM), a potent scavenger of
      reactive oxygen species, either attenuated or abolished IH-evoked augmentation of
      transmitter release during hypoxia. Together, the above results demonstrate that
      IH conditioning increases hypoxia-evoked neurotransmitter release from PC12 cells
      via mechanisms involving mobilization of Ca(2+) from intracellular stores through
      activation of IP(3) receptors. Our findings also suggest that oxidative stress
      plays a central role in IH-induced augmentation of transmitter release from PC12
      cells during acute hypoxia.

PMID- 14657040
TI  - Effects of 18 days of bed rest on leg and arm venous properties.
AB  - Venous function may be altered by bed rest deconditioning. Yet the contribution
      of altered venous compliance to the orthostatic intolerance observed after bed
      rest is uncertain. The purpose of this study was to assess the effect of 18 days
      of bed rest on leg and arm (respectively large and small change in gravitational
      gradients and use patterns) venous properties. We hypothesized that the magnitude
      of these venous changes would be related to orthostatic intolerance. Eleven
      healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and
      after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous
      occlusion plethysmography was used to assess limb venous vascular
      characteristics. Leg venous compliance was significantly decreased after bed rest
      (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100
      ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous
      flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x
      ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P <
      0.05). Maximal lower body negative pressure tolerance, which was expressed as
      cumulative stress index (pressure x time), decreased in all subjects after bed
      rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic
      tolerance was not related to changes in leg venous compliance. In conclusion,
      this study demonstrates that after bed rest, leg venous compliance is reduced and
      leg venous outflow resistance is enhanced. However, these changes are not related
      to measures of orthostatic tolerance; therefore, alterations in venous compliance
      do not to play a major role in orthostatic intolerance after 18 days of head-down
      tilt bed rest.

PMID- 14657042
TI  - Oxidation of combined ingestion of glucose and fructose during exercise.
AB  - The purpose of the present study was to examine whether combined ingestion of a
      large amount of fructose and glucose during cycling exercise would lead to
      exogenous carbohydrate oxidation rates >1 g/min. Eight trained cyclists (maximal
      O(2) consumption: 62 +/- 3 ml x kg(-1) x min(-1)) performed four exercise trials
      in random order. Each trial consisted of 120 min of cycling at 50% maximum power
      output (63 +/- 2% maximal O(2) consumption), while subjects received a solution
      providing either 1.2 g/min of glucose (Med-Glu), 1.8 g/min of glucose (High-Glu),
      0.6 g/min of fructose + 1.2 g/min of glucose (Fruc+Glu), or water. The ingested
      fructose was labeled with [U-(13)C]fructose, and the ingested glucose was labeled
      with [U-(14)C]glucose. Peak exogenous carbohydrate oxidation rates were
      approximately 55% higher (P < 0.001) in Fruc+Glu (1.26 +/- 0.07 g/min) compared
      with Med-Glu and High-Glu (0.80 +/- 0.04 and 0.83 +/- 0.05 g/min, respectively).
      Furthermore, the average exogenous carbohydrate oxidation rates over the 60- to
      120-min exercise period were higher (P < 0.001) in Fruc+Glu compared with Med-Glu
      and High-Glu (1.16 +/- 0.06, 0.75 +/- 0.04, and 0.75 +/- 0.04 g/min,
      respectively). There was a trend toward a lower endogenous carbohydrate oxidation
      in Fruc+Glu compared with the other two carbohydrate trials, but this failed to
      reach statistical significance (P = 0.075). The present results demonstrate that,
      when fructose and glucose are ingested simultaneously at high rates during
      cycling exercise, exogenous carbohydrate oxidation rates can reach peak values of
      approximately 1.3 g/min.

PMID- 14657043
TI  - A bronchial epithelium-derived factor reduces pulmonary vascular tone in the
      newborn rat.
AB  - The factors accounting for the maintenance of a low pulmonary vascular resistance
      postnatally are not completely understood. The aim of this study was to test the
      hypothesis that bronchial epithelium produces a factor capable of relaxing
      adjacent pulmonary arterial smooth muscle. We studied fourth-generation
      intralobar pulmonary arteries and bronchi of 4- to 8-day-old rats. Arteries were
      mounted on a wire myograph, alone or with the adjacent bronchus. The presence of
      the attached bronchus significantly reduced pulmonary artery force generation
      induced by the thromboxane analog (U-46619) or KCl whether the endothelium was
      present or absent (P < 0.01). The converse was not true in that bronchial force
      generation was not affected when studied with the adjacent pulmonary artery.
      Mechanical removal of the bronchial epithelium or addition of the nitric oxide
      (NO) synthase (NOS) nonspecific (N(G)-monomethyl-l-arginine) or the specific
      neuronal NOS (7-nitroindazole) inhibitors increased arterial force generation to
      levels comparable to the isolated artery preparation. Wortmannin, a
      phosphatidylinositol 3-kinase inhibitor, significantly decreased (P < 0.01) NO
      release of pulmonary arteries only when the adjacent bronchus was present. We
      conclude that bronchial epithelium in the newborn rat produces a factor capable
      of lowering pulmonary vascular muscle tone. This relaxant effect can be
      suppressed by NOS and phosphatidylinositol 3-kinase kinase inhibition, suggesting
      an action via NOS phosphorylation and NO release. We speculate that such a
      mechanism may be operative in vivo and plays an important role in control of
      pulmonary vascular resistance in the early postnatal period.

PMID- 14657044
TI  - Oxidation of exogenous glucose, sucrose, and maltose during prolonged cycling
      exercise.
AB  - The purpose of the present study was to investigate whether combined ingestion of
      two carbohydrates (CHO) that are absorbed by different intestinal transport
      mechanisms would lead to exogenous CHO oxidation rates of >1.0 g/min. Nine
      trained male cyclists (maximal O(2) consumption: 64 +/- 2 ml x kg body wt(-1) x
      min(-1)) performed four exercise trials, which were randomly assigned and
      separated by at least 1 wk. Each trial consisted of 150 min of cycling at 50% of
      maximal power output (60 +/- 1% maximal O(2) consumption), while subjects
      received a solution providing either 1.8 g/min of glucose (Glu), 1.2 g/min of
      glucose + 0.6 g/min of sucrose (Glu+Suc), 1.2 g/min of glucose + 0.6 g/min of
      maltose (Glu+Mal), or water. Peak exogenous CHO oxidation rates were
      significantly higher (P < 0.05) in the Glu+Suc trial (1.25 +/- 0.07 g/min)
      compared with the Glu and Glu+Mal trials (1.06 +/- 0.08 and 1.06 +/- 0.06 g/min,
      respectively). No difference was found in (peak) exogenous CHO oxidation rates
      between Glu and Glu+Mal. These results demonstrate that, when a mixture of
      glucose and sucrose is ingested at high rates (1.8 g/min) during cycling
      exercise, exogenous CHO oxidation rates reach peak values of approximately 1.25
      g/min.

PMID- 14657045
TI  - Noninvasive assessment of sympathetic vasoconstriction in human and rodent
      skeletal muscle using near-infrared spectroscopy and Doppler ultrasound.
AB  - The precise role of the sympathetic nervous system in the regulation of skeletal
      muscle blood flow during exercise has been challenging to define in humans,
      partly because of the limited techniques available for measuring blood flow in
      active muscle. Recent studies using near-infrared (NIR) spectroscopy to measure
      changes in tissue oxygenation have provided an alternative method to evaluate
      vasomotor responses in exercising muscle, but this approach has not been fully
      validated. In this study, we tested the hypothesis that sympathetic activation
      would evoke parallel changes in tissue oxygenation and blood flow in resting and
      exercising muscle. We simultaneously measured tissue oxygenation with NIR
      spectroscopy and blood flow with Doppler ultrasound in skeletal muscle of
      conscious humans (n = 13) and anesthetized rats (n = 9). In resting forearm of
      humans, reflex activation of sympathetic nerves with the use of lower body
      negative pressure produced graded decreases in tissue oxygenation and blood flow
      that were highly correlated (r = 0.80, P < 0.0001). Similarly, in resting
      hindlimb of rats, electrical stimulation of sympathetic nerves produced graded
      decreases in tissue oxygenation and blood flow velocity that were highly
      correlated (r = 0.93, P < 0.0001). During rhythmic muscle contraction, the
      decreases in tissue oxygenation and blood flow evoked by sympathetic activation
      were significantly attenuated (P < 0.05 vs. rest) but remained highly correlated
      in both humans (r = 0.80, P < 0.006) and rats (r = 0.92, P < 0.0001). These data
      indicate that, during steady-state metabolic conditions, changes in tissue
      oxygenation can be used to reliably assess sympathetic vasoconstriction in both
      resting and exercising skeletal muscle.

PMID- 14657046
TI  - Breath-by-breath assessment of alveolar gas stores and exchange.
AB  - The volume of O(2) exchanged at the mouth during a breath (Vo(2,m)) is equal to
      that taken up by pulmonary capillaries (Vo(2,A)) only if lung O(2) stores are
      constant. The latter change if either end-expiratory lung volume (EELV), or
      alveolar O(2) fraction (Fa(O(2))) change. Measuring this requires breath-by
      breath (BbB) measurement of absolute EELV, for which we used optoelectronic
      plethysmography combined with measurement of O(2) fraction at the mouth to
      measure Vo(2,A) = Vo(2,m) - (DeltaEELV x Fa(O(2)) + EELV x DeltaFa(O(2))), and
      divided by respiratory cycle time to obtain BbB O(2) consumption (Vo(2)) in seven
      healthy men during incremental exercise and recovery. To synchronize O(2) and
      volume signals, we measured gas transit time from mouthpiece to O(2) meter and
      compared Vo(2) measured during steady-state exercise by using expired gas
      collection with the mean BbB measurement over the same time period. In one
      subject, we adjusted the instrumental response time by 20-ms increments to
      maximize the agreement between the two Vo(2) measurements. We then applied the
      same total time delay (transit time plus instrumental delay = 660 ms) to all
      other subjects. The comparison of pooled data from all subjects revealed r(2) =
      0.990, percent error = 0.039 +/- 1.61 SE, and slope = 1.02 +/- 0.015 (SE). During
      recovery, increases in EELV introduced systematic errors in Vo(2) if measured
      without taking DeltaEELV x Ca(O(2))+EELV x DeltaFa(O(2)) into account. We
      conclude that optoelectronic plethysmography can be used to measure BbB Vo(2)
      accurately when studying BbB gas exchange in conditions when EELV changes, as
      during on- and off-transients.

PMID- 14657047
TI  - New initiatives highlight world AIDS day.

PMID- 14657048
TI  - Food chain of evidence points to brain toxin.

PMID- 14657049
TI  - Researchers explore obesity-cancer link.

PMID- 14657053
TI  - Proposals for US National Health Insurance.

PMID- 14657054
TI  - Proposals for US National Health Insurance.

PMID- 14657055
TI  - Proposals for US National Health Insurance.

PMID- 14657056
TI  - Proposals for US National Health Insurance.

PMID- 14657057
TI  - Proposals for US National Health Insurance.

PMID- 14657058
TI  - Proposals for US National Health Insurance.

PMID- 14657059
TI  - Proposals for US National Health Insurance.

PMID- 14657060
TI  - Guggulipid and cholesterol levels.

PMID- 14657061
TI  - Guggulipid and cholesterol levels.

PMID- 14657062
TI  - Internists' adherence to guidelines for prevention of intravascular catheter
      infections.

PMID- 14657063
TI  - Weight lifting and rupture of silent aortic aneurysms.

PMID- 14657064
TI  - A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy
      for patients with coronary artery disease. The International Verapamil
      Trandolapril Study (INVEST): a randomized controlled trial.
AB  - CONTEXT: Despite evidence of efficacy of antihypertensive agents in treating
      hypertensive patients, safety and efficacy of antihypertensive agents for
      coronary artery disease (CAD) have been discerned only from subgroup analyses in
      large trials. OBJECTIVE: To compare mortality and morbidity outcomes in patients
      with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a
      non-calcium antagonist strategy (NCAS). DESIGN, SETTING, AND PARTICIPANTS:
      Randomized, open label, blinded end point study of 22 576 hypertensive CAD
      patients aged 50 years or older, which was conducted September 1997 to February
      2003 at 862 sites in 14 countries. INTERVENTIONS: Patients were randomly assigned
      to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies
      specified dose and additional drug regimens. Trandolapril and/or
      hydrochlorothiazide was administered to achieve blood pressure goals according to
      guidelines from the sixth report of the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than
      140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg
      (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was
      present. Trandolapril was also recommended for patients with heart failure,
      diabetes, or renal impairment. MAIN OUTCOME MEASURES: Primary: first occurrence
      of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other:
      cardiovascular death, angina, adverse experiences, hospitalizations, and blood
      pressure control at 24 months. RESULTS: At 24 months, in the CAS group, 6391
      patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were
      taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the
      NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking
      hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up
      of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a
      primary outcome event with no statistically significant difference between
      treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98;
      95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was
      similar between groups. The JNC VI blood pressure goals were achieved by 65.0%
      (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1%
      (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients
      achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood
      pressure of less than 90 mm Hg. CONCLUSION: The verapamil-trandolapril-based
      strategy was as clinically effective as the atenolol-hydrochlorothiazide-based
      strategy in hypertensive CAD patients.

PMID- 14657065
TI  - Survival after pancreas transplantation in patients with diabetes and preserved
      kidney function.
AB  - CONTEXT: Solitary pancreas transplantation (ie, pancreas alone or pancreas-after
      kidney) for diabetes mellitus remains controversial due to procedure-associated
      morbidity/mortality, toxicity of immunosuppression, expense, and unproven effects
      on the secondary complications of diabetes. Whether transplantation offers a
      survival advantage over conventional therapies for diabetes is unknown.
      OBJECTIVE: To determine the association between solitary pancreas transplantation
      and survival in patients with diabetes and preserved kidney function. DESIGN,
      SETTING, AND PATIENTS: Retrospective observational cohort study conducted at 124
      transplant centers in the United States, in 11 572 patients with diabetes
      mellitus on the waiting list for pancreas transplantation (pancreas alone,
      pancreas-after-kidney, or simultaneous pancreas-kidney) at the United Network for
      Organ Sharing/Organ Procurement and Transplantation Network between January 1,
      1995, and December 31, 2000. All patients receiving a multiorgan (other than
      simultaneous pancreas-kidney) transplant were excluded, as were those listed for
      solitary pancreas transplantation who had a serum creatinine level greater than 2
      mg/dL (176.8 micromol/L) at time of listing, or who ultimately received a
      simultaneous pancreas-kidney transplant. MAIN OUTCOME MEASURE: All-cause
      mortality within 4 years following transplantation (or within a comparable time
      on the waiting list for the group not undergoing transplantation). RESULTS:
      Overall relative risk of all-cause mortality for transplant recipients (compared
      with patients awaiting the same procedure) over 4 years of follow-up was 1.57
      (95% confidence interval [CI], 0.98-2.53; P =.06) for pancreas transplant alone,
      1.42 (95% CI, 1.03-1.94; P =.03) for pancreas-after-kidney transplant, and 0.43
      (95% CI, 0.39-0.48) for simultaneous pancreas-kidney transplant. Transplant
      patient 1- and 4-year survival rates were 96.5% and 85.2% for pancreas transplant
      alone, respectively, and 95.3% and 84.5% for pancreas-after-kidney transplant,
      while 1- and 4-year survival rates for patients on the waiting list were 97.6%
      and 92.1% for pancreas transplant alone, respectively, and 97.1% and 88.1% for
      pancreas-after-kidney transplant. CONCLUSION: From 1995-2000, survival for those
      with diabetes and preserved kidney function and receiving a solitary pancreas
      transplant was significantly worse compared with the survival of waiting-list
      patients receiving conventional therapy.

PMID- 14657066
TI  - Efficacy and safety of echinacea in treating upper respiratory tract infections
      in children: a randomized controlled trial.
AB  - CONTEXT: Echinacea is a widely used herbal remedy for treatment of upper
      respiratory tract infections (URIs). However, there are few data on the efficacy
      and safety of echinacea in treating URIs in children. OBJECTIVES: To determine if
      Echinacea purpurea is effective in reducing the duration and/or severity of URI
      symptoms in children and to assess its safety in this population. DESIGN,
      SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of
      healthy children 2 to 11 years old recruited from a regional practice-based
      network and an alternative medical center in 4-month periods from 2000 through
      2002. INTERVENTIONS: Study patients were randomized to receive either echinacea
      or placebo for up to 3 URIs over a 4-month period. Study medication was begun at
      the onset of symptoms and continued throughout the URI, for a maximum of 10 days.
      MAIN OUTCOME MEASURES: Primary outcomes were duration and severity of symptoms
      and adverse events recorded by parents; secondary outcomes included peak severity
      of symptoms, number of days of peak severity, number of days of fever, and a
      global assessment of severity of symptoms by parents of study children. RESULTS:
      Data were analyzed on 707 URIs that occurred in 407 children, including 337 URIs
      treated with echinacea and 370 with placebo. There were 79 children who completed
      their study period without having a URI. The median duration of URIs was 9 days
      (95% confidence interval, 8-10 days); there was no difference in duration between
      URIs treated with echinacea or placebo (P =.89). There was also no difference in
      the overall estimate of severity of URI symptoms between the 2 treatment groups
      (median, 33 in both groups; P =.69). In addition, there were no statistically
      significant differences between the 2 groups for peak severity of symptoms (P
      =.68), number of days of peak symptoms (1.60 in the echinacea group and 1.64 in
      the placebo group; P =.97), number of days of fever (0.81 in the echinacea group
      vs 0.64 in the placebo group; P =.09), or parental global assessment of severity
      of the URI (P =.67). Overall, there was no difference in the rate of adverse
      events reported in the 2 treatment groups; however, rash occurred during 7.1% of
      the URIs treated with echinacea and 2.7% of those treated with placebo (P =.008).
      CONCLUSIONS: Echinacea purpurea, as dosed in this study, was not effective in
      treating URI symptoms in patients 2 to 11 years old, and its use was associated
      with an increased risk of rash.

PMID- 14657068
TI  - Discussion of medical errors in morbidity and mortality conferences.
AB  - CONTEXT: Morbidity and mortality conferences in residency programs are intended
      to discuss adverse events and errors with a goal to improve patient care. Little
      is known about whether residency training programs are accomplishing this goal.
      OBJECTIVE: To determine the frequency at which morbidity and mortality conference
      case presentations include adverse events and errors and whether the errors are
      discussed and attributed to a particular cause. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective survey conducted by trained physician observers from
      July 2000 through April 2001 on 332 morbidity and mortality conference case
      presentations and discussions in internal medicine (n = 100) and surgery (n =
      232) at 4 US academic hospitals. MAIN OUTCOME MEASURES: Frequencies of
      presentation of adverse events and errors, discussion of errors, and attribution
      of errors. RESULTS: In internal medicine morbidity and mortality conferences,
      case presentations and discussions were 3 times longer than in surgery
      conferences (34.1 minutes vs 11.7 minutes; P =.001), more time was spent
      listening to invited speakers (43.1% vs 0%; P<.001), and less time was spent in
      audience discussion (15.2% vs 36.6%; P<.001). Fewer internal medicine case
      presentations included adverse events (37 [37%] vs 166 surgery case presentations
      [72%]; P<.001) or errors causing an adverse event (18 [18%] vs 98 [42%],
      respectively; P =.001). When an error caused an adverse event, the error was
      discussed as an error less often in internal medicine (10 errors [48%] vs 85
      errors in surgery [77%]; P =.02). Errors were attributed to a particular cause
      less often in medicine than in surgery conferences (8 [38%] of 21 medicine errors
      vs 88 [79%] of 112 surgery errors; P<.001). In discussions of cases with errors,
      conference leaders in both internal medicine and surgery infrequently used
      explicit language to signal that an error was being discussed and infrequently
      acknowledged having made an error. CONCLUSIONS: Our findings call into question
      whether adverse events and errors are routinely discussed in internal medicine
      training programs. Although adverse events and errors were discussed frequently
      in surgery cases, teachers in both surgery and internal medicine missed
      opportunities to model recognition of error and to use explicit language in error
      discussion by acknowledging their personal experiences with error.

PMID- 14657067
TI  - Valvular dysfunction and carotid, subclavian, and coronary artery disease in
      survivors of hodgkin lymphoma treated with radiation therapy.
AB  - CONTEXT: The majority of patients with Hodgkin lymphoma are young and highly
      curable. This necessitates concern for prevention, diagnosis, and optimal
      management of potential treatment-related complications. OBJECTIVE: To identify
      and quantify the incidence of and factors contributing to long-term cardiac and
      vascular complications after radiation therapy for Hodgkin lymphoma. DESIGN AND
      SETTING: Retrospective study comparing patients treated from 1962 to 1998 at a
      university-based referral center with a matched general population. PATIENTS:
      Four hundred fifteen consecutive patients who fulfilled the inclusion criteria of
      a minimum 2-year follow-up (median, 11.2 years) and whose radiation fields
      included the heart or carotid or subclavian arteries. MAIN OUTCOME MEASURES:
      Multivariable analyses of potential risk factors and observed-to-expected ratios
      for cardiac valve surgery, coronary artery bypass graft surgery, percutaneous
      coronary intervention, or both based on Surveillance, Epidemiology, and End
      Results (SEER) and National Hospital Discharge Survey (NHDS) data. RESULTS: Forty
      two patients (10.4%) developed coronary artery disease at a median of 9 years
      after treatment, 30 patients (7.4%) developed carotid and/or subclavian artery
      disease at a median of 17 years after treatment, and 25 patients (6.2%) developed
      clinically significant valvular dysfunction at a median of 22 years. The most
      common valve lesion was aortic stenosis, which occurred in 14 valves. The
      observed-to-expected ratio for valve surgery was 8.42 (95% confidence interval
      [CI], 3.20-13.65) and the observed-to-expected ratio for coronary artery bypass
      graft surgery or percutaneous coronary intervention was 1.63 (95% CI, 0.98-2.28).
      At least 1 cardiac risk factor was present in all patients who developed coronary
      artery disease. The only treatment-related factor associated with the development
      of coronary artery disease was utilization of a radiation technique that resulted
      in a higher total dose to a portion of the heart (relative risk, 7.8; 95% CI, 1.1
      53.2; P =.04). No specific treatment-related factor was associated with carotid
      or subclavian artery disease or valvular dysfunction. Freedom from any
      cardiovascular morbidity was 88% at 15 years and 84% at 20 years. CONCLUSIONS:
      Among patients treated with radiation therapy for Hodgkin lymphoma, there are
      statistically higher than expected rates of valve surgery and coronary
      revascularization procedures over the next 10 to 20 years. Coronary vascular
      disease is associated with higher radiation doses and traditional coronary heart
      disease risk factors. Noncoronary vascular disease and clinically important
      valvular dysfunction are less well understood complications at 15 to 20 years
      after radiation, requiring surveillance and further study.

PMID- 14657069
TI  - Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer.
AB  - CONTEXT: Cyclin D1 (CCND1) is a key cell cycle regulatory protein, the
      overexpression of which is often found in human tumors and is associated with
      cell proliferation and poor prognosis. A common adenine-to-guanine substitution
      polymorphism (A870G) in the CCND1 gene results in an altered messenger RNA
      transcript and a longer-life protein, which are preferentially encoded by the A
      allele. OBJECTIVE: To test the overall and stage-specific associations of the
      CCND1 870A allele with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: A
      population-based case-control study conducted in the multiethnic population of
      Hawaii between January 1, 1994, and August 31, 1998, which included 504 patients
      with incident colorectal cancer and 624 population-based participants of
      Japanese, white, or Native Hawaiian origin. Participation rates were 58% for
      cases and 52% for controls. Main Outcome Measurement Ethnicity, gene-dosage
      effects, and stage (regional/distant) and subsite (colon vs rectal) of cancer.
      RESULTS: The odds ratio (OR) for the CCND1 870 GA and AA genotypes compared with
      the GG genotype was 1.2 (95% confidence interval [CI], 0.9-1.7) and 1.5 (95% CI,
      1.0-2.1), respectively (P =.03 for gene-dosage effect). These risk estimates were
      significantly greater for patients diagnosed at a regional or distant stage (GA
      vs GG: OR, 1.7; 95% CI, 1.1-2.5 and AA vs GG: OR, 1.9; 95% CI, 1.2-3.1; P =.008
      for gene-dosage effect) compared with those estimates for patients diagnosed at
      an earlier stage (P =.048). In subset analyses, the association between the A
      allele and advanced colorectal cancer was statistically significant in white and
      Hawaiian participants but not in Japanese, and was stronger for rectal cancer.
      CONCLUSION: The CCND1 870A allele may be associated with colorectal cancer, and
      particularly with forms of the disease that result in severe morbidity and
      mortality.

PMID- 14657070
TI  - Does this patient have pulmonary embolism?
AB  - CONTEXT: Experienced clinicians' gestalt is useful in estimating the pretest
      probability for pulmonary embolism and is complementary to diagnostic testing,
      such as lung scanning. However, it is unclear whether recently developed clinical
      prediction rules, using explicit features of clinical examination, are comparable
      with clinicians' gestalt. If so, clinical prediction rules would be powerful
      tools because they could be used by less-experienced health care professionals to
      simplify the diagnosis of pulmonary embolism. Recent studies have shown that the
      combination of a low pretest probability (using a clinical prediction rule) and a
      normal result of a D-dimer test reliably excludes pulmonary embolism without the
      need for further testing. OBJECTIVE: To evaluate and demonstrate the accuracy of
      pretest probability assessment for pulmonary embolism using clinical gestalt vs
      clinical prediction rules. DATA SOURCES: The MEDLINE database was searched for
      relevant articles published between 1966 and March 2003. Bibliographies of
      pertinent articles also were scanned for suitable articles. STUDY SELECTION: To
      be included in the analysis, studies were required to have consecutive,
      unselected patients enrolled; participating physicians in the studies, blinded to
      the results of diagnostic testing, had to estimate pretest probability of
      pulmonary embolism; and validated diagnostic methods had to be used to confirm or
      exclude pulmonary embolism. DATA EXTRACTION: Three reviewers independently
      scanned titles and abstracts for inclusion of studies. An initial MEDLINE search
      identified 1709 studies, of which 16 involving 8306 patients were included in the
      final analysis. DATA SYNTHESIS: A clinical gestalt strategy was used in 7
      studies, and in the low, moderate, and high pretest categories, the rates of
      pulmonary embolism ranged from 8% to 19%, 26% to 47%, and 46% to 91%,
      respectively. Clinical prediction rules were used in 10 studies, and 3% to 28%,
      16% to 46%, and 38% to 98% in the low, moderate, and high pretest probability
      groups, respectively, had pulmonary embolism. CONCLUSIONS: The clinical gestalt
      of experienced clinicians and the clinical prediction rules used by physicians of
      varying experience have shown similar accuracy in discriminating among patients
      who have a low, moderate, or high pretest probability of pulmonary embolism. We
      advocate the use of a clinical prediction rule because it has shown to be
      accurate and can be used by less-experienced clinicians.

PMID- 14657071
TI  - The return on INVEST.

PMID- 14657072
TI  - Isolated pancreas transplantation for type 1 diabetes: a doctor's dilemma.

PMID- 14657073
TI  - MSJAMA. Quarantine.

PMID- 14657074
TI  - MSJAMA. Politics of quarantine in the 19th century.

PMID- 14657075
TI  - MSJAMA. Quarantine and social inequity.

PMID- 14657076
TI  - MSJAMA. Human immunodeficiency virus and quarantine in Cuba.

PMID- 14657077
TI  - MSJAMA. Mathematical models of isolation and quarantine.

PMID- 14657080
TI  - JAMA patient page. Pulmonary embolism.

PMID- 14657081
TI  - Detection of tet(M), tet(O) and tet(S) in tetracycline/minocycline-resistant
      Streptococcus pyogenes bacteraemia isolates.

PMID- 14657082
TI  - Persistence of a clone of glycopeptide-resistant Enterococcus faecalis among
      patients in an intensive care unit of a Greek hospital.
AB  - OBJECTIVES: To investigate an outbreak of glycopeptide-resistant Enterococcus
      faecalis (GREF) in the intensive care unit (ICU) of 'G. Gennimatas' General
      Hospital, Athens, Greece. MATERIALS AND METHODS: Between August 2000 and November
      2001, 20 highly GREF isolates were recovered from severe infections of separate
      patients in the ICU. The isolates were tested by PCR, PFGE, mating experiments
      and plasmid analysis. RESULTS: All isolates carried the vanA gene. Nineteen
      isolates fitted to one clone by macrorestriction analysis with four subclones
      being consecutively detected. Each subclone seemed to predominate for a specific
      time period. Additionally, four GREF isolates related to the ICU clone were
      recovered from other wards of the hospital. CONCLUSIONS: Our findings indicate
      that a monoclonal GREF outbreak persisted for more than 1 year in a large Greek
      hospital. The rate of GREF isolation declined after the application of infection
      control measures.

PMID- 14657083
TI  - Interferon therapy as chemoprevention of hepatocarcinogenesis in patients with
      chronic hepatitis C.
AB  - Hepatocellular carcinoma (HCC) is currently a very common malignancy and its
      incidence is increasing, both in Japan and the USA. Persistent hepatitis C virus
      (HCV) infection is a major risk factor for the development of HCC. A number of
      large-scale retrospective cohort studies have demonstrated that interferon
      therapy reduces the incidence of HCC not only in sustained virological responders
      but also in transient biochemical responders without the elimination of HCV. We
      also demonstrated that retreatment with interferon at certain intervals reduced
      the incidence of HCC in patients with chronic hepatitis C, even if eradication of
      HCV was not achieved by retreatment. We cannot, however, explain how a transient
      normalization of serum alanine aminotransferase levels induced by a maximum 6
      months of interferon treatment reduces the incidence of HCC during the
      progression of chronic hepatitis to cirrhosis or HCC, which requires dozens of
      years. In this article, we discuss how interferon treatment might reduce the
      incidence of HCC even in transient biochemical responders, especially in view of
      antiproliferative or antioxidative activity of interferon-alpha.

PMID- 14657084
TI  - Pharmacological and therapeutic properties of ritonavir-boosted protease
      inhibitor therapy in HIV-infected patients.
AB  - Boosted protease inhibitor regimens combine ritonavir with a second, 'boosted'
      protease inhibitor to enhance patient exposure to the latter agent, thereby
      preventing or overcoming resistance and allowing less frequent dosing,
      potentially improving adherence. The advantages offered by ritonavir boosting are
      primarily attributable to the drug's pharmacokinetic properties. Ritonavir's
      inhibition of the cytochrome P-450 CYP3A4 enzyme reduces the metabolism of
      concomitantly administered protease inhibitors and changes their pharmacokinetic
      parameters, including area under the curve (AUC), maximum concentration (Cmax),
      minimum concentration (Cmin) and half-life (t1/2). As a result, the
      bioavailability of the boosted protease inhibitor is increased and improved
      penetration into HIV reservoirs may be achieved. Boosted protease inhibitor
      regimens that utilize a low dose of ritonavir (100-200 mg) appear to offer the
      best balance of efficacy and tolerability. At this dose, ritonavir boosts the
      bioavailability of the second protease inhibitor without contributing
      significantly to the side effect profile of the regimen. In clinical trials,
      regimens boosted with low dose ritonavir have demonstrated high levels of viral
      suppression in both antiretroviral naive patients and patients who previously
      failed antiretroviral therapy, including protease inhibitor therapy. Side effects
      observed have generally been similar to those associated with the boosted
      protease inhibitor. Based upon their enhanced drug exposure and demonstrated
      efficacy, the boosted ritonavir regimens should be among the first options
      considered for use in clinical practice.

PMID- 14657085
TI  - Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals.
AB  - OBJECTIVES: To determine the rates of mupirocin resistance in staphylococci
      during a 4 year period (1999-2002) in Greece. MATERIALS: A total of 1200
      Staphylococcus aureus and 2760 coagulase-negative staphylococci (CoNS),
      consecutively collected from four Greek hospitals located in different
      geographical areas, were tested for susceptibility to mupirocin using the Etest
      and a reference agar dilution method. RESULTS: Twenty-four S. aureus (2%) and 532
      CoNS (19.2%) were found to be mupirocin-resistant during the study period. High
      level mupirocin resistance was detected in 20 S. aureus (1.6%) and in 440 CoNS
      (15.9%), respectively. No variations in the rates of mupirocin-resistant S.
      aureus in relation to the year of collection were observed. In contrast, the rate
      of mupirocin-resistant CoNS increased dramatically from 9% in 1999, to 14% in
      2000, 20% in 2001 and reached 33% in 2002. PFGE analysis revealed the presence of
      one main clone (A) among mupirocin-resistant S. aureus and two main clones (i and
      a) among Staphylococcus epidermidis isolates. CONCLUSIONS: In Greece, the rate of
      mupirocin-resistant S. aureus has remained low and steady since 1999. The high
      rate of mupirocin-resistant CoNS (33%) in 2002 was due mainly to clonal
      dissemination of epidemic hospital clones.

PMID- 14657086
TI  - Changes in susceptibility to posaconazole in clinical isolates of Candida
      albicans.
AB  - OBJECTIVES: To characterize the molecular mechanisms responsible for reduced
      susceptibility to azoles in Candida albicans clinical isolates. MATERIALS AND
      METHODS: Seven sequential C. albicans isolates were cultured from an AIDS patient
      treated with posaconazole for refractory oropharyngeal candidiasis. Expression
      levels of the CDR1, CDR2 and MDR1 genes, encoding efflux pumps previously
      implicated in azole resistance, and ERG11, encoding the azole target site, were
      monitored using northern blot and real-time PCR. The ERG11 genes from all seven
      isolates were sequenced. RESULTS: The seven closely related isolates exhibited
      significant decreases in susceptibility to fluconazole (MIC >or= 32 mg/L) and
      voriconazole (MIC >or= 2 mg/L) and progressive decreases in susceptibility to
      both posaconazole (isolates 1-4 MIC 0.25 mg/L, isolates 5-7 MIC 2 mg/L) and
      itraconazole (isolates 1-4 MIC 1 mg/L, isolates 5-7 MIC > 8 mg/L). None of the
      isolates exhibited any significant changes in the expression levels of ERG11 or
      the efflux pump genes. All seven isolates had multiple mutations in ERG11;
      isolates one through four each had five missense mutations; four of the resultant
      amino acid changes were previously associated with azole resistance. The fifth
      isolate had an additional novel mutation in one copy of ERG11, resulting in a Pro
      230 to Leu substitution. This mutation was present in both ERG11 genes in the
      last two isolates. Select ERG11 genes were expressed in Saccharomyces cerevisiae,
      the ERG11 allele with all six mutations conferred the highest level of
      posaconazole resistance. CONCLUSIONS: Multiple mutations in ERG11 are required to
      confer decreased susceptibility to posaconazole.

PMID- 14657087
TI  - Study of the toxicity of a new lipid complex formulation of amphotericin B.
AB  - OBJECTIVES: The aim of this study was to evaluate the toxicity of a new lipid
      complex formulation of amphotericin B (LC-AmB) produced by a simple process.
      METHODS: Toxicity was evaluated after daily administration for 21 consecutive
      days in female CD1 mice. Doses of LC-AmB up to 20 mg/kg were used, and compared
      with Fungizone at 0.5 mg/kg and Abelcet at 10 mg/kg. Acute toxicity after a
      single bolus injection was also determined, as well as the haemolytic activity
      and toxicity to mouse macrophages in vitro. RESULTS: LC-AmB reduced both the
      haemolytic activity of amphotericin B and its toxicity towards mouse peritoneal
      macrophages. Its acute toxicity (LD50 > 200 mg/kg in CD1 mice) was similar to
      that in the literature for the least toxic lipid formulations of amphotericin B.
      The relative liver weight increased slightly in mice treated daily with a dose of
      20 mg/kg LC-AmB, as did the kidney weight in this group and the group treated
      with Fungizone. There was also a dose-dependent decrease in the haematocrit with
      all formulations. All treatments caused significant increases in transaminase
      levels. Total hepatic CYP 450 was slightly but not significantly increased in the
      groups treated with 20 mg/kg LC-AmB, Abelcet and Fungizone. However, expression
      of some isoforms of CYP 450 was reduced, the most marked being the hepatic CYP
      3A1 after treatment with 20 mg/kg LC-AmB, Abelcet and Fungizone. The effects on
      hepatic function are probably related to accumulation in organs rich in
      phagocytic cells. CONCLUSION: LC-AmB did not induce any new toxicity compared
      with Abelcet and Fungizone.

PMID- 14657088
TI  - Pharmacokinetic interaction between voriconazole and ciclosporin A following
      allogeneic bone marrow transplantation.
AB  - Voriconazole is a novel antifungal triazole that undergoes extensive oxidative
      metabolization involving several CYP450 isoenzymes. We report the case of a 14
      year-old patient who received voriconazole concomitant with ciclosporin A as
      secondary antifungal prophylaxis after bone marrow transplantation. Temporary
      discontinuation of voriconazole due to worsening liver function tests (LFTs)
      resulted in a sudden drop of ciclosporin A trough levels in blood. Ciclosporin A
      trough levels returned to baseline following normalization of LFTs and re
      institution of voriconazole. This report emphasizes the need for careful
      monitoring and dose adjustments of ciclosporin A in patients receiving
      concomitant voriconazole, and in whom voriconazole is discontinued in order to
      prevent subtherapeutic ciclosporin A levels with the potential consequence of
      graft-versus-host disease.

PMID- 14657089
TI  - The isoleucyl-tRNA synthetase mutation V588F conferring mupirocin resistance in
      glycopeptide-intermediate Staphylococcus aureus is not associated with a
      significant fitness burden.
AB  - OBJECTIVES AND METHODS: Failure to eradicate nasal carriage of a glycopeptide
      intermediate Staphylococcus aureus (strain GISA-2) with mupirocin was recently
      attributed to a mutation that confers low-level mupirocin resistance. To identify
      this mutation the ileS genes of GISA-2 and its mupirocin-susceptible progenitor
      GISA-1 were sequenced. For comparison, the ileS genes of 10 laboratory-derived
      mupirocin-resistant mutants of the GISA strain Mu50 were also examined. The
      fitness of GISA-2 and mupirocin-susceptible GISA-1, as well as Mu50 and its
      mupirocin-resistant derivatives, were compared by evaluation of growth rates and
      performance in mixed-culture competition assays. RESULTS: The point mutation
      V588F in the isoleucyl-tRNA synthetase was identified from the ileS sequences of
      GISA-2 and mupirocin-resistant mutants of Mu50. The V588F mutation was not
      associated with a significant fitness burden. CONCLUSIONS: The low fitness cost
      of the V588F substitution in isoleucyl-tRNA synthetase is consistent with the
      frequent appearance and maintenance of this mutation in mupirocin-resistant
      clinical isolates, including GISA-2.

PMID- 14657090
TI  - Viral receptor blockage by multivalent recombinant antibody fusion proteins:
      inhibiting human rhinovirus (HRV) infection with CFY196.
AB  - Viral receptor blockage by monoclonal antibodies (mAbs) is a common strategy to
      inhibit viral infection; however, no drug candidate acting by this mechanism has
      reached the market so far. Analysis of the experimental and clinical data on a
      receptor-blocking mAb, mAb 1A6, against human rhinovirus (HRV) major receptor
      intercellular adhesion molecule 1 (ICAM-1) reveals that insufficient avidity of
      the mAb is probably the key factor to blame for its unsatisfactory clinical
      efficacy. In this article, we have summarized the recently published work from
      Perlan Therapeutics, Inc. and others that involves creation of multivalent Fab
      fusion proteins against the HRV major receptor ICAM-1. The multivalent Fab fusion
      proteins have exhibited much improved avidities over conventional mAbs, as well
      as superior HRV inhibition in vitro. This work has led to a promising drug
      candidate, CFY196, for prevention and treatment of HRV infections. Multivalent
      recombinant Fab fusion proteins may herald a new generation of potent antiviral
      receptor blockers and other therapeutic molecules.

PMID- 14657091
TI  - Long-term virological outcome and resistance mutations at virological rebound in
      HIV-infected adults on protease inhibitor-sparing highly active antiretroviral
      therapy.
AB  - OBJECTIVE: To assess the durability of the undetectability of HIV plasma viraemia
      (pV) and to determine the factors associated with virological rebound (VR) in HIV
      infected adults on protease inhibitor (PI)-sparing highly active antiretroviral
      therapy (HAART). The development of resistance mutations during virologically
      successful therapy and VR was also analysed. MATERIALS AND METHODS: One hundred
      and twenty-six HIV-infected adults on PI-sparing HAART were prospectively
      followed from April 1998 to December 2002: Group 1, naive for antiretroviral
      drugs (n = 26); Group 2, previously PI-HAART-exposed patients (n = 19); Group 3,
      previously exposed to suboptimal therapy (n = 81). Genotypic resistance tests on
      peripheral blood mononuclear cells or on plasma RNA (when feasible) were carried
      out when undetectable HIV pV was demonstrated for at least 48 weeks.
      Additionally, patients showing a therapy adherence >95% developing VR were also
      tested at rebound, at simplification and during previous suboptimal therapy
      exposure. RESULTS: The median follow-up time was 630 [329-903] days. VR was
      considered as two consecutive pV levels >50 copies/mL. Twenty-two (17.5%)
      patients developed VR. Only therapy adherence <95% was independently associated
      with VR (adjusted hazard ratio: 8.42; 95% CI: 3.33-21.27). Twenty (40%) of the 50
      patients with pV < 50 copies/mL for at least 48 weeks showed at least one
      thymidine-associated mutation (TAM) but none had NNRTI-resistance mutations. Ten
      (83.3%) of 12 available adherent patients showing VR harboured NNRTI-resistance
      associated mutations; 50% of them were considered as wild-type strains at
      simplification time. However, the TAM number and resistance mutations profile
      found on suboptimal exposure were very similar to those found at VR on
      simplification therapy. CONCLUSIONS: PI-sparing HAART allows maintenance of
      successful long-term control of HIV replication, adherence to therapy being the
      main factor associated with VR. However, a small proportion of patients on
      simplification regimen may develop VR regardless of therapy compliance. VR on PI
      sparing HAART is characterized by the emergence of NNRTI cross-resistance
      mutations. Finally, TAMs 'archived' during previous suboptimal exposures are
      partially involved in subsequent VR on simplification HAART.

PMID- 14657092
TI  - All for CD91 and CD91 for all.
AB  - Heat shock proteins interact with antigen-presenting cells through their
      receptor, CD91, eliciting a cascade of events including maturation, activation
      and representation of chaperoned foreign peptides with class I molecules on their
      surface. In turn, this facilitates recognition of non-self leading to induction
      of a cytotoxic T cell response. The abundance of heat shock proteins in tumours
      and their presence in virion coats makes them attractive propositions for use in
      antitumour and antiviral strategies.

PMID- 14657093
TI  - Antibiotic use in animals--prejudices, perceptions and realities.
AB  - Regulatory authorities have suspended the use of some antibiotics as growth
      promoters in animal feed. The subject remains a hotly debated topic around the
      world. Controversy surrounds whether such use in animals presents a real risk of
      increasing resistance in human pathogens, and hence a human health problem. Views
      tend to be polarized. Proponents of the bans point to falling rates of resistance
      in animal and human isolates as a direct result; detractors question whether
      evidence exists for a link between growth promoter use and resistance in human
      pathogens and cite a decline in animal health among the undesirable effects. The
      article by Phillips et al. in this issue puts one view, this article aims to
      consider the merits of the arguments put forward by both sides and looks to a way
      forward.

PMID- 14657094
TI  - Does the use of antibiotics in food animals pose a risk to human health? A
      critical review of published data.
AB  - The use of antibiotics in food animals selects for bacteria resistant to
      antibiotics used in humans, and these might spread via the food to humans and
      cause human infection, hence the banning of growth-promoters. The actual danger
      seems small, and there might be disadvantages to human and to animal health. The
      low dosages used for growth promotion are an unquantified hazard. Although some
      antibiotics are used both in animals and humans, most of the resistance problem
      in humans has arisen from human use. Resistance can be selected in food animals,
      and resistant bacteria can contaminate animal-derived food, but adequate cooking
      destroys them. How often they colonize the human gut, and transfer resistance
      genes is not known. In zoonotic salmonellosis, resistance may arise in animals or
      humans, but human cross-infection is common. The case of campylobacter infection
      is less clear. The normal human faecal flora can contain resistant enterococci,
      but indistinguishable strains in animals and man are uncommon, possibly because
      most animal enterococci do not establish themselves in the human intestine. There
      is no correlation between the carriage of resistant enterococci of possible
      animal origin and human infection with resistant strains. Commensal Escherichia
      coli also exhibits host-animal preferences. Anti-Gram-positive growth promoters
      would be expected to have little effect on most Gram-negative organisms. Even if
      resistant pathogens do reach man, the clinical consequences of resistance may be
      small. The application of the 'precautionary principle' is a non-scientific
      approach that assumes that risk assessments will be carried out.

PMID- 14657095
TI  - Reversible dilated cardiomyopathy related to amphotericin B therapy.
AB  - We describe a patient who developed dilated cardiomyopathy and clinical
      congestive heart failure after 2 months of therapy with amphotericin B (AmB) for
      disseminated coccidioidomycosis. His echocardiographic abnormalities and heart
      failure resolved after posaconazole was substituted for AmB. It is important to
      recognize the rare and potentially reversible toxicity of AmB.

PMID- 14657096
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM.
AB  - The purpose of this announcement is to effect the valid publication of the
      following new names and new combinations under the procedure described in the
      Bacteriological Code (1990 Revision). Authors and other individuals wishing to
      have new names and/or combinations included in future lists should send three
      copies of the pertinent reprint or photocopies thereof to the IJSEM Editorial
      Office for confirmation that all of the other requirements for valid publication
      have been met. It is also a requirement of IJSEM and the ICSP that authors of new
      species, new subspecies and new combinations provide evidence that types are
      deposited in two recognized culture collections in two different countries (i.e.
      documents certifying deposition and availability of type strains). It should be
      noted that the date of valid publication of these new names and combinations is
      the date of publication of this list, not the date of the original publication of
      the names and combinations. The authors of the new names and combinations are as
      given below, and these authors' names will be included in the author index of the
      present issue and in the volume author index. Inclusion of a name on these lists
      validates the name and thereby makes it available in bacteriological
      nomenclature. The inclusion of a name on this list is not to be construed as
      taxonomic acceptance of the taxon to which the name is applied. Indeed, some of
      these names may, in time, be shown to be synonyms, or the organisms may be
      transferred to another genus, thus necessitating the creation of a new
      combination.

PMID- 14657097
TI  - The collapse of the two-kingdom system, the rise of protistology and the founding
      of the International Society for Evolutionary Protistology (ISEP).
AB  - This paper provides a brief summary of the rise and acceptance of protistology as
      a modern, realistic approach to the evolutionary relationships and classification
      of unicellular eukaryotic organisms as well as the origins of the multicellular
      groups. The apparent reasons for the renaissance of this 19th-century concept in
      the 1970s are reviewed, with electron microscopy considered to be the key factor,
      strongly reinforced by molecular phylogenetic studies in the 1980s and 1990s. The
      foundation of the International Society for Evolutionary Protistology in 1975
      accompanied this major alteration in the view of biological diversity. The
      current status of protistology relative to protozoology and phycology is
      discussed.

PMID- 14657098
TI  - Phragmoplastin, green algae and the evolution of cytokinesis.
AB  - Phragmoplast-mediated cell division characterizes the land plants in the
      streptophyte lineage and some species of the green algal orders Coleochaetales,
      Charales and Zygnematales that are basal to that lineage. This type of cell
      division is generally not found in the other green plant lineage, the chlorophyte
      algae. A well-developed phragmoplast-type cell division has been documented,
      however, in two subaerial green algae (Cephaleuros parasiticus and Trentepohlia
      odorata) belonging to the order Trentepohliales--an order that molecular sequence
      data place unequivocally within the chlorophytes rather than streptophytes. Is
      the phragmoplast-mediated cell division of the Trentepohliales a case of homology
      or non-homology? To gain more insight into this question, we are exploring the
      potential phylogenetic information inferred from gene sequences of
      phragmoplastin, a dynamin-like protein that has been associated with cell-plate
      formation during phragmoplast-mediated cytokinesis in land plants. Primers for
      green algae were designed based on an available phragmoplastin sequence from
      soybean and yielded PCR amplifications from the trentepohlialean green algae
      Trentepohlia and Cephaleuros and the leafy liverwort Bazzania: These are the
      first published data for phragmoplastins in algae and liverworts. Analysis of
      phragmoplastin gene sequences in chlorophyte and streptophyte green algae may
      help to chart the evolution of the development of the phragmoplast.

PMID- 14657099
TI  - Comparison of plastid 16S rRNA (rrn16) genes from Helicosporidium spp.: evidence
      supporting the reclassification of Helicosporidia as green algae (Chlorophyta).
AB  - The Helicosporidia are invertebrate pathogens that have recently been identified
      as non-photosynthetic green algae (Chlorophyta). In order to confirm the algal
      nature of the genus Helicosporidium, the presence of a retained chloroplast
      genome in Helicosporidia cells was investigated. Fragments homologous to plastid
      16S rRNA (rrn16) genes were amplified successfully from cellular DNA extracted
      from two different Helicosporidium isolates. The fragment sequences are 1269 and
      1266 bp long, are very AT-rich (60.7 %) and are similar to homologous genes
      sequenced from non-photosynthetic green algae. Maximum-parsimony, maximum
      likelihood and neighbour-joining methods were used to infer phylogenetic trees
      from an rrn16 sequence alignment. All trees depicted the Helicosporidia as sister
      taxa to the non-photosynthetic, pathogenic alga Prototheca zopfii. Moreover, the
      trees identified Helicosporidium spp. as members of a clade that included the
      heterotrophic species Prototheca spp. and the mesotrophic species Chlorella
      protothecoides. The clade is always strongly supported by bootstrap values,
      suggesting that all these organisms share a most recent common ancestor.
      Phylogenetic analyses inferred from plastid 16S rRNA genes confirmed that the
      Helicosporidia are non-photosynthetic green algae, close relatives of the genus
      Prototheca (Chlorophyta, Trebouxiophyceae). Such phylogenetic affinities suggest
      that Helicosporidium spp. are likely to possess Prototheca-like organelles and
      organelle genomes.

PMID- 14657100
TI  - Highly organized structure in the non-coding region of the psbA minicircle from
      clade C Symbiodinium.
AB  - The chloroplast genes of dinoflagellates are distributed among small, circular
      dsDNA molecules termed minicircles. In this paper, we describe the structure of
      the non-coding region of the psbA minicircle from Symbiodinium: DNA sequence was
      obtained from five Symbiodinium strains obtained from four different coral host
      species (Goniopora tenuidens, Heliofungia actiniformis, Leptastrea purpurea and
      Pocillopora damicornis), which had previously been determined to be closely
      related using LSU rDNA region D1/D2 sequence analysis. Eight distinct sequence
      blocks, consisting of four conserved cores interspersed with two metastable
      regions and flanked by two variable regions, occurred at similar positions in all
      strains. Inverted repeats (IRs) occurred in tandem or "twin" formation within two
      of the four cores. The metastable regions also consisted of twin IRs and had
      modular behaviour, being either fully present or completely absent in the
      different strains. These twin IRs are similar in sequence to double-hairpin
      elements (DHEs) found in the mitochondrial genomes of some fungi, and may be
      mobile elements or may serve a functional role in recombination or replication.
      Within the central unit (consisting of the cores plus the metastable regions),
      all IRs contained perfect sequence inverses, implying they are highly evolved.
      IRs were also present outside the central unit but these were imperfect and
      possessed by individual strains only. A central adenine-rich sequence most
      closely resembled one in the centre of the non-coding part of Amphidinium
      operculatum minicircles, and is a potential origin of replication. Sequence
      polymorphism was extremely high in the variable regions, suggesting that these
      regions may be useful for distinguishing strains that cannot be differentiated
      using molecular markers currently available for Symbiodinium.

PMID- 14657101
TI  - Foraminifera and Cercozoa share a common origin according to RNA polymerase II
      phylogenies.
AB  - Phylogenetic analysis of small and large subunits of rDNA genes suggested that
      Foraminifera originated early in the evolution of eukaryotes, preceding the
      origin of other rhizopodial protists. This view was recently challenged by the
      analysis of actin and ubiquitin protein sequences, which revealed a close
      relationship between Foraminifera and Cercozoa, an assemblage of various filose
      amoebae and amoeboflagellates that branch in the so-called crown of the SSU rDNA
      tree of eukaryotes. To further test this hypothesis, we sequenced a fragment of
      the largest subunit of the RNA polymerase II (RPB1) from five foraminiferans, two
      cercozoans and the testate filosean Gromia oviformis. Analysis of our data
      confirms a close relationship between Foraminifera and Cercozoa and points to
      Gromia as the closest relative of Foraminifera.

PMID- 14657102
TI  - The excavate protozoan phyla Metamonada Grasse emend. (Anaeromonadea,
      Parabasalia, Carpediemonas, Eopharyngia) and Loukozoa emend. (Jakobea,
      Malawimonas): their evolutionary affinities and new higher taxa.
AB  - It is argued here that the anaerobic protozoan zooflagellate Parabasalia,
      Carpediemonas and Eopharyngia (diplomonads, enteromonads, retortamonads)
      constitute a holophyletic group, for which the existing name Trichozoa is adopted
      as a new subphylum. Ancestrally, Trichozoa probably had hydrogenosomes, stacked
      Golgi dictyosomes, three anterior centrioles and one posterior centriole: the
      typical tetrakont pattern. It is also argued that the closest relatives of
      Trichozoa are Anaeromonada (Trimastix, oxymonads), and the two groups are
      classified as subphyla of a revised phylum Metamonada. Returning Parabasalia and
      Anaeromonadea to Metamonada, as in Grasse's original classification, simplifies
      classification of the kingdom Protozoa by reducing the number of phyla within
      infrakingdom Excavata from five to four. Percolozoa (Heterolobosea plus
      Percolatea classis nov.) and Metamonada are probably both ancestrally
      quadriciliate with a kinetid of four centrioles attached to the nucleus; the few
      biciliates among them are probably secondarily derived. Metamonada ancestrally
      probably had two divergent centriole pairs, whereas, in Percolozoa, all four
      centrioles are parallel. It is suggested that Discicristata (Percolozoa,
      Euglenozoa) are holophyletic, ancestrally with two parallel centrioles. In the
      phylum Loukozoa, Malawimonadea classis nov. is established for Malawimonas (with
      a new family and order also) and Diphyllatea classis nov., for Diphylleida
      (Diphylleia, Collodictyon), is transferred back to Apusozoa. A new class, order
      and family are established for the anaerobic, biciliate, tricentriolar
      Carpediemonas, transferring it from Loukozoa to Trichozoa because of its triply
      flanged cilia; like Retortamonas, it may be secondarily biciliate--its unique
      combination of putative hydrogenosomes and flanged cilia agree with molecular
      evidence that Carpediemonas is sister to Eopharyngia, diverging before their
      ancestor lost hydrogenosomes and acquired a cytopharynx. Removal of anaeromonads
      and Carpediemonas makes Loukozoa more homogeneous, being basically biciliate,
      aerobic and free-living, in contrast to Metamonada. A new taxon-rich rRNA tree
      supports holophyly of Discicristata and Trichozoa strongly, holophyly of
      Metamonada and Excavata and paraphyly of Loukozoa weakly. Mitochondria were
      probably transformed into hydrogenosomes independently in the ancestors of
      lyromonad Percolozoa and Metamonada and further reduced in the ancestral
      eopharyngian. Evidence is briefly discussed that Metamonada and all other
      excavates share a photosynthetic ancestry with Euglenozoa and are secondarily non
      photosynthetic, as predicted by the cabozoan hypothesis for a single secondary
      symbiogenetic acquisition of green algal plastids by the last common ancestor of
      Euglenozoa and Cercozoa. Excavata plus core Rhizaria (Cercozoa, Retaria) probably
      form an ancestrally photophagotrophic clade. The origin from a benthic loukozoan
      ancestor of the characteristic cellular features of Percolozoa and Euglenozoa
      through divergent adaptations for feeding on or close to surfaces is also
      discussed.

PMID- 14657103
TI  - Cytoskeletal organization, phylogenetic affinities and systematics in the
      contentious taxon Excavata (Eukaryota).
AB  - An overview of the controversial proposal for the major eukaryote taxon
      "Excavata" is presented. Excavata is predicted to include at least ten distinct
      groups: jakobids, Malawimonas, Trimastix, Carpediemonas, retortamonads,
      diplomonads, Heterolobosea, oxymonads, parabasalids and Euglenozoa. These
      "excavates" have broadly similar flagellar apparatus organizations, for which a
      "universal" terminology is provided. Most, but not all, of these organisms share
      a distinctive suspension-feeding groove, as well as some or all of a set of seven
      other proposed cytoskeletal apomorphies. Cladistic analyses of morphological data
      do not resolve high-level relationships within Excavata. Excavate-rich molecular
      phylogenies recover some robust clades, but do not support or strongly refute the
      monophyly of Excavata. A partial classification for excavates is presented, with
      phylogenetic diagnoses for Excavata and for two novel taxon names, Fornicata
      (Carpediemonas, retortamonads, diplomonads) and Preaxostyla (Trimastix,
      oxymonads).

PMID- 14657104
TI  - Thialkalivibrio nitratireducens sp. nov., a nitrate-reducing member of an
      autotrophic denitrifying consortium from a soda lake.
AB  - Strain ALEN 2(T) was isolated from a mixed culture capable of complete
      autotrophic denitrification with thiosulfate as electron donor at pH 10; the
      mixed culture was enriched from sediment from Lake Fazda (Wadi Natrun, Egypt), a
      hypersaline alkaline lake. The isolate had large, non-motile, coccoid or barrel
      shaped cells with intracellular sulfur globules. The bacterium was obligately
      chemolithoautotrophic. It grew with reduced sulfur compounds aerobically and
      anaerobically with nitrate as electron acceptor, nitrate being reduced to
      nitrite. It was moderately halophilic and obligately alkaliphilic. On the basis
      of genetic analysis and its unique phenotype, strain ALEN 2(T) (=DSM
      14787(T)=UNIQEM 213(T)) is proposed as the type strain of a novel species of the
      genus Thialkalivibrio, Thialkalivibrio nitratireducens.

PMID- 14657105
TI  - Elevation of Mycobacterium tuberculosis subsp. caprae Aranaz et al. 1999 to
      species rank as Mycobacterium caprae comb. nov., sp. nov.
AB  - Mycobacterium tuberculosis complex isolates recovered from goats were originally
      classified as Mycobacterium tuberculosis subsp. caprae; however, this subspecies
      was recently reclassified as Mycobacterium bovis subsp. caprae. Besides
      biochemical (sensitivity to pyrazinamide) and epidemiological features, strains
      of this unusual member of the M. tuberculosis complex show a special combination
      of pncA, oxyR, katG and gyrA gene polymorphisms. Sequence analysis of the gyrB
      gene in these strains reveals special nucleotide substitutions not found in other
      members of the M. tuberculosis complex that can be used to differentiate caprine
      mycobacterial strains from M. bovis and other members of the M. tuberculosis
      complex. M. tuberculosis subsp. caprae now appears not to be restricted to
      Spanish goats, as strains of this organism have been isolated from cattle, wild
      boar and pigs. Its occurrence has also been reported in France, Austria and
      Germany. Two studies on the evolution of the M. tuberculosis complex based on the
      presence/absence of regions of difference have shown that the group of caprine
      isolates (or its ancestor) is older than M. bovis (or its ancestor). These
      findings reinforce the original suggestion that the caprine mycobacterial strains
      are a taxon of the M. tuberculosis complex, independent of M. bovis. Within the
      current context of the existing nomenclature of the M. tuberculosis complex, it
      is proposed that M. tuberculosis subsp. caprae be elevated to species status, as
      Mycobacterium caprae comb. nov., sp. nov.

PMID- 14657106
TI  - Soehngenia saccharolytica gen. nov., sp. nov. and Clostridium amygdalinum sp.
      nov., two novel anaerobic, benzaldehyde-converting bacteria.
AB  - Two anaerobic, benzaldehyde-converting bacteria were isolated from an anaerobic
      upflow anaerobic sludge bed (UASB)-reactor treating potato starch waste water.
      Strain BOR-Y(T) converted benzaldehyde to benzoate and benzylalcohol in
      approximately equimolar concentrations. Benzaldehyde conversion did not support
      growth. Strain BOR-Y(T) was Gram-positive and rod-shaped, and its cells were
      slightly thickened in the middle. The strain was a mesophilic spore-former that
      grew between 15 and 40 degrees C, with optimum growth at 30-37 degrees C. The
      optimum pH for growth was pH 7.0. Strain BOR-Y(T) grew on a wide range of
      carbohydrates and some other carbon sources including yeast extract, cysteine and
      serine. The G+C content of its DNA was 42 mol%. According to physiological
      characteristics and 16S rRNA gene sequence analysis, confirmed by DNA-DNA
      hybridization with its phylogenetic neighbours, strain BOR-Y(T) belongs to a
      novel genus of cluster XII of the clostridia, namely Soehngenia; the name
      Soehngenia saccharolytica is proposed for the type species (type strain BOR
      Y(T)=DSM 12858(T)=ATCC BAA-502(T)). Strain BR-10(T) reduced benzaldehyde to
      benzylalcohol. This conversion was coupled to growth. In a medium containing
      yeast extract, the presence of benzaldehyde resulted in the accumulation of more
      than twofold more cells. Strain BR-10(T) was a Gram-positive organism that was
      characterized by oval- or rod-shaped cells with oval ends, which occurred singly,
      in pairs or sometimes in chains. The strain was moderately thermophilic and grew
      between 20 and 60 degrees C, with optimum growth at 45 degrees C. The optimum pH
      for growth was between pH 7.0 and 7.5. Strain BR-10(T) grew on a wide range of
      carbon sources including carbohydrates, yeast extract, casein and some amino
      acids. The G+C content of its DNA was 32 mol%. As determined by 16S rRNA gene
      sequence analysis, strain BR-10(T) represents a novel species of cluster XIVa of
      the clostridia; the name Clostridium amygdalinum is proposed for this novel
      species (type strain BR-10(T)=DSM 12857(T)=ATCC BAA-501(T)).

PMID- 14657107
TI  - Sulfurimonas autotrophica gen. nov., sp. nov., a novel sulfur-oxidizing epsilon
      proteobacterium isolated from hydrothermal sediments in the Mid-Okinawa Trough.
AB  - A novel mesophilic, sulfur- and thiosulfate-oxidizing bacterium, strain OK10(T),
      was isolated from deep-sea sediments at the Hatoma Knoll in the Mid-Okinawa
      Trough hydrothermal field. Cells of strain OK10(T) were short rods, each being
      motile by means of a single polar flagellum. The isolate grew at 10-40 degrees C
      (optimum 25 degrees C) and pH 4.5-9.0 (optimum pH 6.5). It grew
      chemolithoautotrophically with elemental sulfur, sulfide and thiosulfate as sole
      electron donors and oxygen as electron acceptor. Molecular hydrogen did not
      support growth. The G+C content of the genomic DNA of strain OK10(T) was 35.2
      mol%. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that the
      isolate belonged to the epsilon-Proteobacteria. On the basis of its physiological
      and molecular characteristics, strain OK10(T) (=ATCC BAA-671(T)=JCM 11897(T))
      represents the sole species of a new genus, Sulfurimonas, for which the name
      Sulfurimonas autotrophica is proposed.

PMID- 14657108
TI  - Pseudoalteromonas sagamiensis sp. nov., a marine bacterium that produces protease
      inhibitors.
AB  - A marine bacterium producing protease inhibitors was isolated from neritic sea
      water and was studied phenotypically, genotypically and phylogenetically. This
      bacterium (strain B-10-31(T)) produced three types of protease inhibitor, namely,
      marinostatin, monastatin and leupeptin, which were considerably different in
      terms of their chemical structure and properties. Strain B-10-31(T) was a rod
      shaped, non-spore-forming, Gram-negative, strictly aerobic bacterium that was
      motile by means of one polar flagellum. The strain required Na(+) for growth and
      exhibited optimal growth at 27 degrees C, pH 8.0 and 2 % (w/v) NaCl. It utilized
      various substrates, such as D-glucose, maltose, maltotriose, N-acetylglucosamine,
      L-threonine, L-serine, L-arginine, L-proline, L-alpha-alanine and L-glutamate, as
      the sole energy source. Ubiquinone-8 was the major respiratory quinone. The major
      fatty acids were C(16 : 0), C(16 : 1) omega7c, C(16 : 1) omega9c and C(18 : 1)
      omega7c. The G+C content of the DNA of strain B-10-31(T) was 42.0 mol%.
      Phylogenetic analysis, based on 16S rDNA sequences, showed that the strain
      clustered in the gamma-Proteobacteria. The aerobic marine bacterium
      Pseudoalteromonas bacteriolytica was the species most closely related to the new
      isolate (90.4 % 16S rDNA sequence similarity); other described species in the
      gamma-Proteobacteria cluster showed low levels of sequence similarity with strain
      B-10-31(T) (<90 %). Based on the above results, it is proposed that the novel
      marine bacterium should be classified as a new species, for which the name
      Pseudoalteromonas sagamiensis (type strain B-10-31(T)=JCM 11461(T)=DSM 14643(T))
      is proposed.

PMID- 14657109
TI  - Vibrio superstes sp. nov., isolated from the gut of Australian abalones Haliotis
      laevigata and Haliotis rubra.
AB  - Five alginolytic, facultatively anaerobic, non-motile bacteria were isolated from
      the gut of abalones Haliotis laevigata and Haliotis rubra. Phylogenetic analyses
      based on 16S rDNA data indicated that these strains are related closely to Vibrio
      halioticoli (98 % 16S rDNA sequence similarity). DNA-DNA hybridization and
      fluorescent amplified fragment length polymorphism fingerprinting demonstrated
      that the five strains constituted a single species that was different from all
      currently known vibrios. The name Vibrio superstes sp. nov. (type strain, LMG
      21323(T)=IAM 15009(T)=G3-29(T); DNA G+C content, 48.0-48.9 mol%) is proposed to
      encompass this novel taxon. Several phenotypic features were disclosed that
      discriminate V. superstes from other Vibrio species: V. superstes sp. nov. and V.
      halioticoli can be differentiated on the basis of 17 traits (indole production,
      beta-galactosidase test and assimilation of 15 carbon compounds).

PMID- 14657110
TI  - Achromobacter insolitus sp. nov. and Achromobacter spanius sp. nov., from human
      clinical samples.
AB  - A polyphasic taxonomic study (employing whole-cell protein and fatty acid
      analyses, 16S rDNA sequencing, DNA-DNA hybridization, determination of DNA G+C
      content, antibiotic susceptibility testing and extensive phenotypic
      characterization) was performed on 10 isolates that appeared to be related to
      Alcaligenes faecalis. The isolates were recovered from diverse environments that
      included human clinical samples. 16S rDNA sequence analysis indicated that these
      isolates belonged to the genus ACHROMOBACTER: Whole-cell protein analysis
      distinguished two groups, which were confirmed by DNA-DNA hybridization. Based on
      the results of this study, the organisms were classified as two novel
      Achromobacter species, Achromobacter insolitus sp. nov. (type strain, LMG
      6003(T)) and Achromobacter spanius sp. nov. (type strain, LMG 5911(T)).
      Achromobacter insolitus can be distinguished from Achromobacter spanius by its
      ability to grow on acetamide and to assimilate mesaconate and aconitate, and by
      its inability to assimilate diaminobutane. Various tests allow the
      differentiation of both novel species from other Achromobacter species, including
      growth on acetamide, denitrification and assimilation of D-glucose, D-xylose,
      mesaconate, aconitate and diaminobutane.

PMID- 14657111
TI  - Kerstersia gyiorum gen. nov., sp. nov., a novel Alcaligenes faecalis-like
      organism isolated from human clinical samples, and reclassification of
      Alcaligenes denitrificans Ruger and Tan 1983 as Achromobacter denitrificans comb.
      nov.
AB  - A polyphasic taxonomic study was performed on nine isolates recovered from
      various human clinical samples. Phenotypically, these isolates resembled
      Alcaligenes faecalis. Whole-cell protein analysis distinguished two different
      species, and this was confirmed by DNA-DNA hybridizations. Cellular fatty acid
      analysis and 16S rDNA sequence analysis indicated that these isolates were
      related to the genera Alcaligenes, Bordetella, Achromobacter and Pigmentiphaga
      and belonged to the family Alcaligenaceae. On the basis of the results of this
      study, the organisms were classified in a novel genus, Kerstersia gen. nov. This
      genus comprises one species, Kerstersia gyiorum sp. nov. (type strain LMG
      5906(T)=API 184-2-84(T)=CCUG 47000(T)), and several unnamed isolates. The DNA G+C
      content of members of the genus Kerstersia is between 61.5 and 62.9 mol%. On the
      basis of previously published DNA-DNA hybridization results and data from
      chemotaxonomic studies, it is proposed that Alcaligenes denitrificans Ruger and
      Tan 1983 be reclassified as Achromobacter denitrificans comb. nov.

PMID- 14657112
TI  - Molecular signatures in protein sequences that are characteristic of
      cyanobacteria and plastid homologues.
AB  - Fourteen conserved indels (i.e. inserts or deletions) have been identified in 10
      widely distributed proteins that appear to be characteristic of cyanobacterial
      species and are not found in any other group of bacteria. These signatures
      include three inserts of 6, 7 and 28 aa in the DNA helicase II (UvrD) protein, an
      18-21 aa insert in DNA polymerase I, a 14 aa insert in the enzyme ADP-glucose
      pyrophosphorylase, a 3 aa insert in the FtsH protein, an 11-13 aa insert in
      phytoene synthase, a 5 aa insert in elongation factor-Tu, two deletions of 2 and
      7 aa in ribosomal S1 protein, a 2 aa insert in the SecA protein, a 1 aa deletion
      and a 6 aa insert in the enzyme inosine-5'-monophosphate dehydrogenase and a 1 aa
      deletion in the major sigma factor. These signatures, which are flanked by
      conserved regions, provide molecular markers for distinguishing cyanobacterial
      taxa from all other bacteria and they should prove helpful in the identification
      of cyanobacterial species, simply on the basis of the presence or absence of
      these markers in the corresponding proteins. The signatures in six of these
      proteins (SecA, elongation factor-Tu, ADP-glucose pyrophosphorylase, phytoene
      synthase, FtsH and ribosomal S1 protein) are also commonly present in plastid
      homologues from plants and algae (chlorophytes, chromophytes and rhodophytes),
      indicating their specific relationship to cyanobacteria and supporting their
      endosymbiotic origin from these bacteria. In phylogenetic trees based on a number
      of these proteins (SecA, UvrD, DNA polymerase I, elongation factor-Tu) that were
      investigated, the available cyanobacterial homologues grouped together with high
      affinity (>95 % bootstrap value), supporting the view that the cyanobacterial
      phylum is monophyletic and that the identified signatures were introduced in a
      common ancestor of this group.

PMID- 14657113
TI  - Anaerolinea thermophila gen. nov., sp. nov. and Caldilinea aerophila gen. nov.,
      sp. nov., novel filamentous thermophiles that represent a previously uncultured
      lineage of the domain Bacteria at the subphylum level.
AB  - Two thermophilic, Gram-negative, non-spore-forming, multicellular filamentous
      micro-organisms were isolated from thermophilic granular sludge in an upflow
      anaerobic sludge blanket reactor treating fried soybean-curd manufacturing waste
      water (strain UNI-1(T)) and from a hot spring sulfur-turf in Japan (strain STL-6
      O1(T)). The filaments were longer than 100 microm and of 0.2-0.3 microm (strain
      UNI-1(T)) or 0.7-0.8 microm (strain STL-6-O1(T)) in width. Strain UNI-1(T) was a
      strictly anaerobic organism. The optimum temperature for growth was around 55
      degrees C; growth occurred in the range 50-60 degrees C. The optimum pH for
      growth was around 7.0; growth occurred in the range pH 6.0-8.0. Strain STL-6
      O1(T) was a facultatively aerobic bacterium. The optimum temperature for growth
      was around 55 degrees C; growth occurred in the range 37-65 degrees C. The
      optimum pH for growth was around 7.5-8.0; growth occurred in the range pH 7.0
      9.0. The two organisms grew chemo-organotrophically on a number of carbohydrates
      and amino acids in the presence of yeast extract. The G+C content of the DNA of
      strains UNI-1(T) and STL-6-O1(T) was 54.5 and 59.0 mol%, respectively. Major
      cellular fatty acids for strain UNI-1(T) were C(16 : 0), C(15 : 0), C(14 : 0) and
      C(18 : 0), whereas those for strain STL-6-O1(T) were C(18 : 0), C(16 : 0), C(17 :
      0) and iso-C(17 : 0). MK-10 was the major quinone from aerobically grown STL-6
      O1(T) cells. Phylogenetic analyses based on 16S rDNA sequences revealed that both
      strains belong to an uncultured, previously recognized clone lineage of the
      phylum Chloroflexi (formerly known as green non-sulfur bacteria). These
      phenotypic and genetic properties suggested that each strain should be classified
      into a new independent genus; hence, the names Anaerolinea thermophila and
      Caldilinea aerophila are proposed for strains UNI-1(T) (=JCM 11387(T)=DSM
      14523(T)) and STL-6-O1(T)(=JCM 11388(T)=DSM 14525(T)), respectively. These
      strains represent the type and sole species of the genera Anaerolinea and
      Caldilinea, respectively.

PMID- 14657114
TI  - Fulvimarina pelagi gen. nov., sp. nov., a marine bacterium that forms a deep
      evolutionary lineage of descent in the order "Rhizobiales".
AB  - Three brownish-yellow bacterial strains were isolated from the western Sargasso
      Sea by high-throughput culturing methods and characterized by polyphasic
      approaches. All isolates were Gram-negative, strictly aerobic,
      chemoheterotrophic, non-motile short rods that contained carotenoid pigments.
      Phylogenetic analyses based on 16S rRNA gene sequences, DNA-DNA hybridization and
      DNA G+C content, along with phenotypic characteristics, revealed that they
      belonged to the same species. The strains utilized a wide range of substrates,
      including pentoses, hexoses, oligosaccharides, sugar alcohols, organic acids and
      amino acids, as sole carbon sources. The DNA G+C content of the isolates ranged
      from 57.6 to 59.9 mol%. The predominant cellular fatty acid constituent was C(18
      : 1)omega7c, whilst C(16 : 0), C(18 : 0) and C(19 : 0)omega8c cyclo were also
      abundant. The organism related most closely to these strains, as determined by
      16S rDNA sequence comparison, was the recently described species Aurantimonas
      coralicida (93.3-93.8 % similarity). Phylogenetic analyses indicated that the
      strains formed a distinct and deep evolutionary lineage of descent, together with
      A. coralicida, within the order "Rhizobiales" of the alpha-Proteobacteria. This
      lineage could not be associated with any of the ten known families in the order
      "Rhizobiales". From polyphasic evidence, it is proposed that the strains be
      placed into a novel genus and species, Fulvimarina pelagi gen. nov., sp. nov.
      (type strain, HTCC2506(T)=ATCC BAA-666(T)=KCTC 12091(T)=DSM 15513(T)).

PMID- 14657115
TI  - Phylogenetic relationships and genotyping of the genus Streptococcus by sequence
      determination of the RNase P RNA gene, rnpB.
AB  - The rnpB gene is universally present in bacterial species and encodes the RNA
      subunit of endoribonuclease P. In this study, rnpB was sequenced in 50 type
      strains and 29 additional strains of the genus Streptococcus. Putative secondary
      structure models and possible interactions in RNase P RNA molecules are
      discussed. Phylogenetic relationships were studied and Bayesian, maximum
      parsimony and minimum-evolution analyses supported six main clades that comprised
      22 of the 50 species analysed. Phylogenetic inference was also studied for the
      16S rRNA gene; it indicated a similar tree topology, but with weaker support
      values than for rnpB. Combined analysis of rnpB and 16S resulted in a phylogeny
      with significantly better support. Variability in the rnpB and 16S genes among
      all type strains, calculated as Shannon-Wiener information index values, was 0.45
      for rnpB and 0.15 for 16S. Intraspecies proximity was assessed by principal
      coordinate analysis of rnpB for 32 strains of six closely related species (two
      clades) and showed species-specific clusters, but heterogeneity occurred in two
      species. It can be concluded that the rnpB gene is suitable for phylogenetic
      analysis of closely related taxa and has potential as a tool for species
      discrimination.

PMID- 14657116
TI  - Idiomarina loihiensis sp. nov., a halophilic gamma-Proteobacterium from the
      Lo'ihi submarine volcano, Hawai'i.
AB  - During an investigation of bacterial diversity at hydrothermal vents on the
      Lo'ihi Seamount, Hawai'i, a novel bacterium (designated L2-TR(T)) was cultivated,
      which shares 99.9 % 16S rRNA gene sequence similarity over 1415 nt with an
      uncultured eubacterium from sediment at a depth of 11 000 m in the Mariana
      Trench. The nearest cultivated neighbour of L2-TR(T), however, is Idiomarina
      abyssalis KMM 227(T), with which it shares 98.9 % 16S rRNA sequence similarity.
      L2-TR(T) differed from I. abyssalis KMM 227(T) in several phenotypic respects,
      including growth at 46 degrees C and in medium that contained 20 % (w/v) NaCl.
      DNA-DNA hybridization data showed that L2-TR(T) did not belong to the species I.
      abyssalis (43.4 % DNA-DNA reassociation). Cells of L2-TR(T) were Gram-negative
      rods, 0.35 microm wide and 0.7-1.0 microm long, which were occasionally up to 1.8
      microm in length. Cells were motile by a single polar or subpolar flagellum. The
      major fatty acid in L2-TR(T) was iso-C(15 : 0) (32.6 %). The DNA G+C content was
      47.4 mol%. Phenotypic and genotypic analyses indicated that L2-TR(T) could be
      assigned to the genus Idiomarina but, based on significant phenotypic and
      genotypic differences, constituted a novel species within this genus, Idiomarina
      loihiensis sp. nov., of which L2-TR(T) (=ATCC BAA-735(T)=DSM 15497(T)) is the
      type strain.

PMID- 14657117
TI  - Arthrobacter gandavensis sp. nov., for strains of veterinary origin.
AB  - Three strains of a previously undescribed, Gram-positive, coryneform bacterium,
      which were isolated from cattle, were subjected to polyphasic taxonomic analysis.
      Comparative 16S rRNA gene sequencing revealed that the unknown isolates were
      members of the genus Arthrobacter and were phylogenetically closely related to
      Arthrobacter luteolus. However, DNA-DNA hybridization indicated that the strains
      belonged to a new sub-lineage within the genus Arthrobacter. The unknown isolates
      can be distinguished from related species by biochemical tests. It is proposed
      that the Arthrobacter-like bacteria of veterinary origin should be classified in
      the genus Arthrobacter as Arthrobacter gandavensis sp. nov., with the type strain
      LMG 21285(T) (=DSM 15046(T)).

PMID- 14657118
TI  - Oceanisphaera litoralis gen. nov., sp. nov., a novel halophilic bacterium from
      marine bottom sediments.
AB  - A polyphasic taxonomic study was performed to characterize a new bacterial
      isolate, designated KMM 3654(T), from a marine bottom sand sample. The strain was
      Gram-negative, encapsulated, aerobic, moderately halophilic and grew between 0.5
      and 10 % NaCl and at 4-42 degrees C. Its DNA G+C content was 56.4 mol%. Isolate
      KMM 3654(T) was phylogenetically closely related to members of the genus
      Oceanimonas, showing 96.7 and 95.6 % 16S rRNA gene sequence similarity to
      Oceanimonas doudoroffii DSM 7028(T) and Oceanimonas baumannii ATCC 700832(T),
      respectively. Strain KMM 3654(T) shared some physiological and chemotaxonomic
      properties with these two Oceanimonas species, but differed from them in
      morphology, growth at 4 degrees C, urease activity, weak phenol degradation and
      utilization of phenylacetate. On the basis of phenotypic and phylogenetic
      evidence, Oceanisphaera litoralis gen. nov., sp. nov. is proposed, with the type
      strain KMM 3654(T) (=DSM 15406(T)).

PMID- 14657119
TI  - Luteococcus sanguinis sp. nov., isolated from human blood.
AB  - An unusual catalase-positive, Gram-positive, coccus-shaped bacterium that
      originated from a human blood specimen was subjected to a polyphasic taxonomic
      study. Cell-wall murein and lipid composition analyses indicated that the unknown
      isolate was a member of the genus Luteococcus. The results of comparative 16S
      rRNA gene sequence analysis were consistent with chemotaxonomic findings and
      showed that the unidentified bacterium represents a hitherto unknown sublineage
      within the genus Luteococcus that is closely related to, but distinct from,
      Luteococcus japonicus. On the basis of both phenotypic and phylogenetic evidence,
      it is proposed that the unknown bacterium from human blood should be classified
      as Luteococcus sanguinis sp. nov., with the type strain CCUG 33897(T) (=CIP
      107216(T)).

PMID- 14657120
TI  - Gene sequences useful for predicting relatedness of whole genomes in bacteria.
AB  - Thirty-two protein-encoding genes that are distributed widely among bacterial
      genomes were tested for the potential usefulness of their DNA sequences in
      assigning bacterial strains to species. From publicly available data, it was
      possible to make 49 pairwise comparisons of whole bacterial genomes that were
      related at the genus or subgenus level. DNA sequence identity scores for eight of
      the genes correlated strongly with overall sequence identity scores for the
      genome pairs. Even single-gene alignments could predict overall genome
      relatedness with a high degree of precision and accuracy. Predictions could be
      refined further by including two or three genes in the analysis. The proposal
      that sequence analysis of a small set of protein-encoding genes could reliably
      assign novel strains or isolates to bacterial species is strongly supported.

PMID- 14657121
TI  - Oceanicaulis alexandrii gen. nov., sp. nov., a novel stalked bacterium isolated
      from a culture of the dinoflagellate Alexandrium tamarense (Lebour) Balech.
AB  - Five bacterial strains were isolated from a non-toxigenic strain of the marine
      dinoflagellate Alexandrium tamarense (Lebour) Balech CCMP 116 (NEPCC C116),
      during a survey of the diversity of bacteria associated with paralytic shellfish
      toxin-producing cultures of Alexandrium spp. (Dinophyta). All strains were
      strictly aerobic, Gram-negative, straight or curved rods. Cells were dimorphic,
      with stalks (or prosthecae) and non-motile or non-stalked and motile, by means of
      a single polar flagellum. The bacteria grew best at salt concentrations ranging
      from 2 to 10 % and growth occurred at 10 degrees C, but not at 50 degrees C. The
      G+C content of the chromosomal DNA of the strains was determined to be 61-62
      mol%. Major cellular fatty acids of the bacteria presented a unique profile. 16S
      rRNA gene sequence analysis showed the five strains to be related to genera of
      budding bacteria of marine origin in the 'Alphaproteobacteria', namely, Hirschia,
      Maricaulis and Hyphomonas, although they exhibited substantial differences in
      morphology, substrate utilization and fatty acid profile to members of these
      genera. The five strains are proposed to comprise a new species of a new genus,
      Oceanicaulis alexandrii gen. nov., sp. nov., the type strain of which is C116
      18(T) (=DSM 11625(T)=NCIMB 13905(T)).

PMID- 14657122
TI  - Rapid identification of filamentous actinomycetes to the genus level using genus
      specific 16S rRNA gene restriction fragment patterns.
AB  - A rapid method for identifying filamentous actinomycete genera was developed
      based on 16S rRNA gene restriction fragment patterns. The patterns were generated
      by using specific restriction endonucleases to perform in silico digestions on
      the 16S rRNA gene sequences of all validly published filamentous actinomycete
      species. The method was applied to identifying actinomycete isolates from soil.
      Amplified 16S rDNA of soil actinomycetes was restricted with selected
      endonucleases and electrophoresed on agarose gels. The restriction fragment
      patterns of the unknown isolates were easily compared to the established
      patterns. Significantly, the genus Streptomyces could be differentiated from all
      other actinomycete genera by using only four restriction endonucleases, Sau3AI,
      AsnI, KpnI and SphI. This could be achieved in a time period of as little as a
      week, following PCR-template DNA isolation by a simple method. The identification
      method allowed unknown, non-Streptomyces soil isolates to be identified to a
      genus or small subgroup of genera. The genera in these subgroups could, in some
      cases, be distinguished by virtue of colony-morphology differences.

PMID- 14657123
TI  - Aeromicrobium marinum sp. nov., an abundant pelagic bacterium isolated from the
      German Wadden Sea.
AB  - An obligately salt-dependent Gram-positive bacterium, designated strain T2(T),
      was isolated from surface waters of the German Wadden Sea. The organism exhibited
      optimum growth at salt concentrations similar to that of sea water. On the basis
      of phenotypic, chemotaxonomic and phylogenetic differences, it is concluded that
      strain T2(T) (=DSM 15272(T)=LMG 21768(T)) is the first marine species of the
      genus Aeromicrobium to be identified, for which the name Aeromicrobium marinum is
      proposed. It is also the first described marine bacterium within the family
      Nocardioidaceae. Strain T2(T) is a rod-shaped, aerobic, heterotrophic bacterium
      containing LL-diaminopimelic acid in the peptidoglycan and MK-9(H(4)) as the
      major menaquinone. The bacterium is characterized by high proportions of the
      fatty acids palmitic acid, oleic acid, tuberculostearic acid and hydroxypalmitic
      acid. DNA-DNA hybridization analysis showed the marine bacterium to display 29.1
      % relatedness with Aeromicrobium fastidiosum DSM 10552(T) and 44.4 % relatedness
      with Aeromicrobium erythreum DSM 8599(T). A. marinum was demonstrated to be an
      abundant member of the pelagic bacterial community in the German Wadden Sea since
      it represented about 1 % of the total bacterial population as revealed by dot
      blot hybridization and most-probable-number counts.

PMID- 14657124
TI  - "Candidatus Phytoplasma oryzae", a novel phytoplasma taxon associated with rice
      yellow dwarf disease.
AB  - In addition to rice yellow dwarf (RYD) phytoplasma, several phytoplasmas infect
      gramineous plants, including rice orange leaf, bermuda grass white leaf,
      brachiaria grass white leaf and sugarcane white leaf phytoplasmas. To investigate
      whether the RYD phytoplasma is a discrete, species-level taxon, several isolates
      of the aforementioned phytoplasmas were analysed using PCR-amplified 16S rDNA
      sequences. Two RYD isolates, RYD-J(T) and RYD-Th, were almost identical (99.2 %),
      but were distinct (similarities of 96.3-97.9 %) from other phytoplasma isolates
      of the RYD 16S-group. The notion that the RYD phytoplasma constitutes a unique
      taxon is also supported by its unique insect vector (Nephotettix sp.), its unique
      host plant in nature (rice) and its limited geographical distribution (Asia). In
      Southern blot analysis, chromosomal and extrachromosomal DNA probes of the RYD
      phytoplasma reportedly did not hybridize with those of closely related
      phytoplasmas. These properties of the RYD phytoplasma clearly indicate that it
      represents a novel taxon, 'Candidatus Phytoplasma oryzae'.

PMID- 14657125
TI  - Methanocaldococcus indicus sp. nov., a novel hyperthermophilic methanogen
      isolated from the Central Indian Ridge.
AB  - An autotrophic, hyperthermophilic methanogen, strain SL43(T), was isolated from a
      deep-sea hydrothermal chimney sample collected on the Central Indian Ridge at a
      depth of 2420 m. The coccoid, surface-layer-carrying, Gram-negative-staining
      cells were heavily flagellated and exhibited a slight tumbling motility. The
      temperature range for growth at pH 6.5 was 50-86 degrees C, with optimum growth
      at 85 degrees C. The optimum pH for growth was 6.6 and the optimum NaCl
      concentration for growth was 30 g l(-1). The novel isolate used H(2) and CO(2) as
      the only substrates for growth and produced methane. Selenium and yeast extract
      stimulated growth significantly. In the presence of CO(2) and H(2), the organism
      reduced elemental sulfur to hydrogen sulfide. Growth was inhibited by
      chloramphenicol and rifampicin, but not by ampicillin, kanamycin, penicillin or
      streptomycin. The G+C content of the genomic DNA was 30.7 mol%. On the basis of
      16S rRNA gene sequence analysis, this organism was most closely related to
      Methanocaldococcus infernus ME(T) (3.2 % distance). Its phylogenetic
      distinctiveness was confirmed by RFLP analysis of the 16S rDNA, a reliable tool
      for differentiating hyperthermophilic methanococci. On the basis of phylogenetic
      and physiological characteristics, it is proposed that strain SL43(T) (=DSM
      15027(T)=JCM 11886(T)) be designated as the type strain of a novel species,
      Methanocaldococcus indicus sp. nov.

PMID- 14657126
TI  - Dialister invisus sp. nov., isolated from the human oral cavity.
AB  - Six strains of anaerobic, Gram-negative coccobacilli isolated from the root
      canals of patients with endodontic infections (five strains) and from a deep
      periodontal pocket (one strain) were subjected to a comprehensive range of
      phenotypic and genetic tests and were found to comprise a homogeneous group.
      Following 16S rRNA gene sequence analysis, they were found to be most closely
      related to Dialister pneumosintes, with 93 % sequence similarity between the two
      taxa. A novel species, Dialister invisus sp. nov., is proposed. Biochemically,
      the species is largely unreactive and is asaccharolytic, with only traces of
      acetate and propionate detected as metabolic end-products. The G+C content of the
      DNA of D. invisus strains is 45-46 mol%. The type strain is E7.25(T) (=CCUG
      47026(T)=DSM 15470(T)).

PMID- 14657127
TI  - rDNA sequence analyses of Streptococcus dysgalactiae subsp. equisimilis isolates
      from pigs.
AB  - The nucleotide sequences of 16S and 23S rRNA genes (rDNA) were determined for 11
      isolates of Streptococcus dysgalactiae subsp. equisimilis from slaughtered pigs
      with endocarditis, arthritis or lymphadenitis and strain ATCC 35666, designated
      as a strain of subspecies equisimilis. The sequences of each of the genes were
      compared phylogenetically with the corresponding sequences of S. dysgalactiae
      subsp. dysgalactiae ATCC 43078(T) and ATCC 27957, which were also determined in
      this study. Based on the 16S rDNA analysis, the isolates of S. dysgalactiae
      subsp. equisimilis were divided into two distinct groups, designated groups 1 and
      2. S. dysgalactiae subsp. equisimilis ATCC 35666 was closely related to the group
      2 strains. The S. dysgalactiae subsp. dysgalactiae strains seemed to be
      associated with the group 1 strains, which was not consistent with the
      conventional subspecific classification of S. dysgalactiae. In contrast, the 23S
      rDNA analysis distinguished S. dysgalactiae subsp. dysgalactiae strains from
      subsp. equisimilis strains. This inconsistency between phylogenies based on 16S
      and 23S rDNA indicates that 23S rDNA is a more rigid marker for determining the
      phylogenetic relationships and taxonomic position of these organisms than is 16S
      rDNA.

PMID- 14657128
TI  - Balnearium lithotrophicum gen. nov., sp. nov., a novel thermophilic, strictly
      anaerobic, hydrogen-oxidizing chemolithoautotroph isolated from a black smoker
      chimney in the Suiyo Seamount hydrothermal system.
AB  - A novel, extremely thermophilic bacterium, designated strain 17S(T), was isolated
      from a deep-sea hydrothermal vent chimney at the Suiyo Seamount in the Izu-Bonin
      Arc, Japan. The cells were rods with no apparent motility, most of which were
      narrow in the middle in the exponential-growth phase and had several polar
      flagella at both ends. Growth was observed between 45 and 80 degrees C (optimum
      temperature, 70-75 degrees C; doubling time, 80 min) and between pH 5.0 and 7.0
      (optimum pH, 5.4). The isolate was a strictly anaerobic chemolithoautotroph that
      was capable of using molecular hydrogen as its sole energy source and carbon
      dioxide as its sole carbon source. Elemental sulfur (S(0)) was required for
      growth as an electron acceptor. The G+C content of the genomic DNA was 34.6 mol%.
      Phylogenetic analysis based on 16S rDNA sequences indicated that the isolate was
      related to Thermovibrio ruber ED11/3LLK(T) and Desulfurobacterium
      thermolithotrophum BSA(T), whilst it appeared to be a novel lineage prior to the
      divergence of these genera. This isolate could also be differentiated from both
      T. ruber ED11/3LLK(T) and D. thermolithotrophum BSA(T) on the basis of
      physiological properties. The name Balnearium lithotrophicum gen. nov., sp. nov.
      is proposed for this isolate (type strain, 17S(T)=JCM 11970(T)=ATCC BAA-736(T)).

PMID- 14657129
TI  - Brachybacterium muris sp. nov., isolated from the liver of a laboratory mouse
      strain.
AB  - A coccoid- to ovoid-shaped, Gram-positive bacterial strain, designated C3H-21(T),
      was isolated from the liver of the laboratory mouse strain C3H/He and
      characterized by a polyphasic approach. The peptidoglycan type was variation
      A4gamma with meso-diaminopimelic acid as the diagnostic cell-wall diamino acid
      and an interpeptide bridge of D-asp-D-Glu. The isolate contained menaquinone MK-7
      (88 %) as the major component of the quinone system and minor amounts of
      menaquinone MK-8 (9 %) and menaquinone MK-6 (3 %). The polar lipid profile
      consisted of diphosphatidylglycerol, phosphatidylglycerol, unidentified
      glycolipids and unidentified phospholipids. The fatty acid profile contained
      predominantly anteiso-C(15 : 0) and significant amounts of iso-C(16 : 0), iso
      C(14 : 0,) anteiso-C(17 : 0) and C(19 : 0). The polyamine pattern consisted of
      spermine and spermidine as the major compounds. Genomic fingerprints clearly
      distinguished strain C3H-21(T) from other Brachybacterium species. The isolate
      shared the highest 16S rDNA sequence similarities with members of the genus
      Brachybacterium, in particular Brachybacterium sacelli LMG 20345(T),
      Brachybacterium nesterenkovii DSM 9573(T), Brachybacterium rhamnosum LMG
      19848(T), Brachybacterium alimentarium CNRZ 925(T) and Brachybacterium fresconis
      LMG 20336(T) (97.8-97.2 %). The results of biochemical/physiological
      characterization, chemotaxonomic characteristics and REP-PCR-generated
      fingerprints demonstrated that the isolate represents a novel species of the
      genus Brachybacterium, for which the name Brachybacterium muris (type strain C3H
      21(T)=DSM 15460(T)=CCM 7047(T)) [corrected] is proposed.

PMID- 14657130
TI  - Thermomonas fusca sp. nov. and Thermomonas brevis sp. nov., two mesophilic
      species isolated from a denitrification reactor with poly(epsilon-caprolactone)
      plastic granules as fixed bed, and emended description of the genus Thermomonas.
AB  - Previously, 22 aerobic Gram-negative bacteria were isolated from biofilms growing
      on granules of the synthetic polyester poly(epsilon-caprolactone); the granules
      were used as a fixed bed in a denitrification reactor. All the strains showed
      similar fatty acid profiles. The 16S rRNA gene sequences of five strains were
      phylogenetically related to Thermomonas spp. Repetitive extragenic palindromic
      DNA-PCR (REP-PCR) fingerprinting revealed four groups, and DNA hybridizations
      between representative strains showed that the strains belonged to two new
      species within the genus Thermomonas, for which the names Thermomonas fusca (type
      strain LMG 21737(T)=DSM 15424(T)) and Thermomonas brevis (type strain LMG
      21746(T)=DSM 15422(T)) are proposed. Both species are able to grow at low
      temperatures, but not at 50 degrees C, and are non-haemolytic. Both species can
      be differentiated by several other phenotypic features from earlier described
      species of the genus Thermomonas. Cell extracts contain mainly branched fatty
      acids, with C(15 : 0) iso, C(17 : 1) iso omega9c, C(11 : 0) iso 3OH and C(11 : 0)
      iso as main constituents. The G+C content of the DNA of the novel species is
      between 67.6 and 68.7 mol%.

PMID- 14657131
TI  - Mesonia algae gen. nov., sp. nov., a novel marine bacterium of the family
      Flavobacteriaceae isolated from the green alga Acrosiphonia sonderi (Kutz) Kornm.
AB  - The taxonomic position of four heterotrophic, aerobic, Gram-negative, non-motile
      and moderately halophilic marine bacteria, isolated from the green alga
      Acrosiphonia sonderi (Kutz) Kornm, was established. 16S rDNA sequence analysis
      indicated that the strains studied are members of the family Flavobacteriaceae,
      in which they form a distinct lineage. On the basis of phenotypic,
      chemotaxonomic, genotypic and phylogenetic data, the novel bacteria were
      classified as Mesonia algae gen. nov., sp. nov. The type strain is KMM 3909(T)
      (=KCTC 12089(T)=CCUG 47092(T)).

PMID- 14657132
TI  - Rheinheimera pacifica sp. nov., a novel halotolerant bacterium isolated from deep
      sea water of the Pacific.
AB  - An aerobic, Gram-negative, non-fermentative, rod-shaped, motile, non-pigmented
      bacterium, KMM 1406(T), was isolated from a sample of Pacific deep sea water and
      investigated for phenotypic characteristics, chemotaxonomic features and
      phylogenetic relationships. The deep-sea isolate exhibited growth in 0-8 % (w/v)
      NaCl and at 4-37 degrees C, hydrolytic activity on gelatin, Tween 80 and starch
      and lack of D-glucose utilization. The major fatty acids were C(16 : 0), C(16 :
      1)omega9c, C(17 : 1)omega8c and C(18 : 1)omega7c. The DNA G+C content was 49.6
      mol%. 16S rRNA gene sequence analysis revealed that strain KMM 1406(T) was
      related closely to Rheinheimera baltica DSM 14885(T) within the gamma
      Proteobacteria, with 96.8 % sequence similarity. On the basis of phenotypic and
      molecular data, a novel species, Rheinheimera pacifica sp. nov., is proposed. The
      type strain is KMM 1406(T) (=IAM 15043(T)=JCM 12090(T)=NRIC 0539(T)=CCUG
      46544(T)).

PMID- 14657133
TI  - Herbaspirillum lusitanum sp. nov., a novel nitrogen-fixing bacterium associated
      with root nodules of Phaseolus vulgaris.
AB  - Several bacterial strains were isolated from root nodules of Phaseolus vulgaris
      plants grown in a soil from Portugal. The strains were Gram-negative, aerobic,
      curved rod-shaped and motile. The isolates were catalase- and oxidase-positive.
      The TP-RAPD (two-primer randomly amplified polymorphic DNA) patterns of all
      strains were identical, suggesting that they belong to the same species. The
      complete 16S rDNA sequence of a representative strain was obtained and
      phylogenetic analysis based on the neighbour-joining method indicated that this
      bacterium belongs to the beta-Proteobacteria and that the closest related genus
      is Herbaspirillum. The DNA G+C content ranged from 57.9 to 61.9 mol%. Growth was
      observed with many different carbohydrates and organic acids including caprate,
      malate, citrate and phenylacetate. No growth was observed with maltose, meso
      inositol, meso-erythritol or adipate as sole carbon source. According to the
      phenotypic and genotypic data obtained in this work, the bacterium represents a
      novel species of the genus Herbaspirillum, and the name Herbaspirillum lusitanum
      sp. nov. is proposed. The type strain is P6-12(T) (=LMG 21710(T)=CECT 5661(T)).

PMID- 14657134
TI  - Psychrobacter okhotskensis sp. nov., a lipase-producing facultative psychrophile
      isolated from the coast of the Okhotsk Sea.
AB  - A facultatively psychrophilic bacterium, strain MD17(T), which hydrolyses lipids
      at 5 degrees C, was isolated from the Monbetsu coast of the Okhotsk Sea in
      Hokkaido, Japan, when ice carried by the cold current came to the area. The
      isolate is an aerobic, non-motile coccobacillus that reduces nitrate to nitrite
      and hydrolyses Tweens 20, 40, 60 and 80, but not gelatin, DNA or alginic acid.
      The isolate grows at 0 degrees C, but not at temperatures higher than 36 degrees
      C; its optimum growth temperature is 25 degrees C. It grows in the presence of 0
      10 % NaCl. Its major isoprenoid quinone is ubiquinone-8 (Q-8) and its DNA G+C
      content is 46.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that strain MD17(T) is closely related to Psychrobacter glacincola DSM
      12194(T) (99.0 % similarity) and Psychrobacter immobilis DSM 7229(T) (98.7 %
      similarity). DNA-DNA hybridization revealed 45.9 % relatedness between strain
      MD17(T) and P. immobilis ATCC 43116(T) and 33.4 % between strain MD17(T) and P.
      glacincola ATCC 700754(T). Based on physiological and biochemical
      characteristics, phylogenetic position (as determined by 16S rRNA gene sequence
      analysis) and DNA-DNA relatedness, it is concluded that the isolate should be
      designated as a novel species, for which the name Psychrobacter okhotskensis sp.
      nov. is proposed. The type strain is MD17(T) (=NCIMB 13931(T)=JCM 11840(T)).

PMID- 14657135
TI  - Propionicimonas paludicola gen. nov., sp. nov., a novel facultatively anaerobic,
      Gram-positive, propionate-producing bacterium isolated from plant residue in
      irrigated rice-field soil.
AB  - Two propionate-producing strains (Wd(T) and Wf) that were isolated anaerobically
      from plant residue of irrigated rice-field soil in Japan were characterized
      phenotypically and phylogenetically. The growth rate of strain Wd(T) was very
      slow in basal medium, but both growth and propionate production were stimulated
      significantly by the addition of cyanocobalamin. Strain Wf grew well in basal
      medium and produced substantial amounts of fermentation products, including
      propionate. Other phenotypic and phylogenetic characteristics of the two isolates
      were almost identical. Both were facultatively anaerobic, but much better growth
      was observed under anaerobic conditions. Cells were Gram-positive, non-motile,
      non-spore-forming and pleomorphic rods with irregular V- or crescent-shaped cell
      arrangements. Fermentation products from glucose in the presence of excess
      cyanocobalamin were acetate, lactate, a small amount of succinate and CO(2), in
      addition to propionate. Both oxidase and catalase activities were negative. The
      strains possessed meso-diaminopimelic acid in their peptidoglycan and their major
      cellular fatty acids were C(13 : 0), anteiso-C(15 : 0) and C(15 : 0). The
      isolates had high genomic DNA G+C contents (68.7 and 67.4 mol%, respectively).
      Menaquinones MK-9(H(4)) and MK-10(H(4)) were the predominant respiratory
      quinones. Phylogenetic analysis based on 16S rDNA sequences placed both strains
      in the Actinobacteria, with Micropruina glycogenica as their closest relative
      (sequence similarity values of 95.8 and 95.7 %, respectively). Microlunatus
      phosphovorus and Friedmanniella antarctica were also related closely to the
      isolates. As their morphological, physiological and chemotaxonomic
      characteristics were distinctly different from those of any related species,
      Propionicimonas paludicola gen. nov., sp. nov. is proposed to accommodate these
      strains. The type strain of the novel species is Wd(T) (=JCM 11933(T)=DSM
      15597(T)).

PMID- 14657136
TI  - Emended description of Janibacter terrae, including ten dibenzofuran-degrading
      strains and Janibacter brevis as its later heterotypic synonym.
AB  - Ten Gram-positive strains that degraded dibenzofuran belonged to one homogeneous
      cluster with common biochemical and chemotaxonomic properties. The strains
      included the previously described strains [Terrabacter sp.] DPO 360 and DPO 1361
      and were isolated from different locations in central Europe. They all shared
      menaquinone MK-8(H(4)) and meso-diaminopimelic acid in the cell wall and showed
      the same cellular fatty acid, polar lipid and RiboPrint patterns. Chemotaxonomic
      properties, as well as DNA G+C content (72.8 mol%), were consistent with those
      described for the genus Janibacter. Analysis of 16S rDNA sequences suggested a
      close relationship to Janibacter terrae and Janibacter brevis. DNA-DNA
      hybridization of two dibenzofuran-degrading strains (DPO 360 and DPO 1361) and
      the type strains of J. terrae and J. brevis revealed that these strains belong to
      the same species. An emended description of the species J. terrae is given. J.
      brevis is a later heterotypic synonym of J. terrae.

PMID- 14657137
TI  - Staphylococcus nepalensis sp. nov., isolated from goats of the Himalayan region.
AB  - Four coagulase-negative, novobiocin-resistant cocci, designated CW1(T), PM34, MM3
      and RW78, were isolated from the respiratory tract of goats kept in the Himalayan
      region. The four isolates were assigned to a single species on the basis of
      almost identical biochemical and physiological traits, protein profiles obtained
      after SDS-PAGE and identical genomic fingerprints generated after enterobacterial
      repetitive intergenic consensus (ERIC)-PCR. Strain CW1(T) showed highest 16S rDNA
      sequence similarities to Staphylococcus cohnii subsp. urealyticus ATCC 49330(T),
      Staphylococcus saprophyticus subsp. saprophyticus ATCC 15305(T), S. cohnii subsp.
      cohnii ATCC 29974(T), Staphylococcus arlettae ATCC 43957(T), Staphylococcus
      gallinarum ATCC 35539(T), Staphylococcus succinus ATCC 700337(T) and
      Staphylococcus xylosus ATCC 29971(T) (99.0, 98.8, 98.8, 98.4, 98.2, 98.1 and 98.1
      %, respectively), indicating its classification within the genus Staphylococcus.
      The polar lipid composition, fatty acid profiles, quinone systems and diagnostic
      cell-wall diamino acid were in agreement with the characteristics of the genus
      Staphylococcus. DNA-DNA hybridization with closely related Staphylococcus species
      suggested that strain CW1(T) represents an as-yet unrecognized species. Based on
      these results, a novel species of the genus Staphylococcus is described,
      Staphylococcus nepalensis sp. nov. The type strain is CW1(T) (=DSM 15150(T)=CCM
      7045(T)) and the most dissimilar strain is PM34 (=DSM 15151=CCM 7046).

PMID- 14657138
TI  - Planococcus maritimus sp. nov., isolated from sea water of a tidal flat in Korea.
AB  - Two Gram-positive, motile cocci, strains TF-9(T) and TF-16, were isolated from
      sea water of a tidal flat in Korea. Phylogenetic analysis based on 16S rDNA
      sequences showed that the strains fall within the radiation of the cluster
      comprising Planococcus citreus and Planococcus kocurii, and this cluster joined
      the clade comprising Planomicrobium species and Planococcus alkanoclasticus and
      Planococcus psychrophilus with a high bootstrap resampling value. Strains TF-9(T)
      and TF-16 contained MK-8, MK-7 and MK-6 as the predominant menaquinones. The
      major fatty acid was anteiso-C(15 : 0). The DNA G+C contents of strains TF-9(T)
      and TF-16 were respectively 48 and 49 mol%. The level of 16S rDNA identity
      between strains TF-9(T) and TF-16 was 98.9 %. Strain TF-9(T) and TF-16
      respectively exhibited levels of 16S rDNA identity of 97.2-98.4 and 96.9-99.5 %
      to the type strains of Planococcus kocurii, Planococcus citreus and Planococcus
      antarcticus. The mean level of DNA-DNA relatedness between strains TF-9(T) and TF
      16 was 36.7 %. Strains TF-9(T) and TF-16 respectively exhibited levels of DNA-DNA
      relatedness of 7.1-43.4 and 3.5-80.9 % to Planococcus citreus DSM 20549(T),
      Planococcus kocurii DSM 20747(T) and Planococcus antarcticus DSM 14505(T). On the
      basis of the phenotypic, phylogenetic and genomic data, strain TF-9(T) (=KCCM
      41587(T)=JCM 11543(T)) should be placed as a novel species of the genus
      Planococcus, for which the name Planococcus maritimus sp. nov. is proposed, and
      strain TF-16 should be classified as a member of Planococcus citreus.

PMID- 14657139
TI  - Evolution of symbiosis in the Vibrionaceae: a combined approach using molecules
      and physiology.
AB  - The family Vibrionaceae is considered to be one of the most diverse and well
      studied groups of bacteria. Here, evolution is assessed within the Vibrionaceae
      to determine whether multiple origins of eukaryotic associations have occurred
      within this diverse group of bacteria. Analyses were based on a large molecular
      dataset, along with a matrix that consisted of 100 biochemical and restriction
      digest characters. By using direct optimization methods to analyse both datasets
      individually and in combination, a total-evidence cladogram has been produced,
      which supports the hypothesis that several important symbionts (both mutualistic
      and pathogenic) within the Vibrionaceae are not monophyletic. This leads us to
      consider that symbiosis (and subsequently, associations with Eukarya) has evolved
      multiple times within the Vibrionaceae lineage.

PMID- 14657140
TI  - Corynebacterium suicordis sp. nov., from pigs.
AB  - Nineteen strains of Gram-positive, non-motile, non-spore-forming, catalase
      positive, rod-shaped bacteria isolated from pigs were characterized by using
      biochemical, molecular chemical and molecular genetic methods. Two distinct
      groups of organisms were discerned, based on their colonial morphology, CAMP
      (Christie-Atkins-Munch-Petersen) reaction and numerical profile by using the API
      Coryne system. The first group (13 strains) gave a doubtful discrimination
      between Corynebacterium striatum and Corynebacterium amycolatum, whilst the
      second group (six strains) were identified tentatively as Corynebacterium
      urealyticum. Comparative 16S rRNA gene sequencing studies demonstrated that all
      of the isolates belonged phylogenetically to the genus CORYNEBACTERIUM: The first
      group of organisms was highly similar to Corynebacterium testudinoris with
      respect to 16S rRNA gene sequences and physiological characteristics, whereas the
      remaining six isolates formed a hitherto unknown subline within the genus,
      associated with a small subcluster of species that included Corynebacterium
      auriscanis and its close relatives. The unknown Corynebacterium sp. was
      distinguished readily from these and other species of the genus by biochemical
      tests. Based on both phenotypic and phylogenetic evidence, it is proposed that
      the new isolates from pigs should be classified as a novel species,
      Corynebacterium suicordis sp. nov. The type strain is P81/02(T) (=CECT
      5724(T)=CCUG 46963(T)).

PMID- 14657141
TI  - Kitasatospora putterlickiae sp. nov., isolated from rhizosphere soil, transfer of
      Streptomyces kifunensis to the genus Kitasatospora as Kitasatospora kifunensis
      comb. nov., and emended description of Streptomyces aureofaciens Duggar 1948.
AB  - A polyphasic study was undertaken to establish the taxonomic position of a
      rhizosphere isolate that had been assigned provisionally to the genus
      Kitasatospora. The organism, isolate F18-98(T), was found to have chemical and
      morphological properties that were consistent with its classification as a
      Kitasatospora strain. Direct 16S rDNA sequence data confirmed the taxonomic
      position of the strain, following the generation of phylogenetic trees by using
      three treeing algorithms. The organism formed a 16S rDNA subclade with
      Kitasatospora azatica and Streptomyces kifunensis, but was distinguished readily
      from the latter by using a combination of biochemical and physiological
      properties. Genotypic and phenotypic data show that strain F18-98(T) should be
      classified in the genus Kitasatospora as a novel species, for which the name
      Kitasatospora putterlickiae sp. nov. is proposed; the type strain has been
      deposited in culture collections as strain F18-98(T) (=DSM 44665(T)=NCIMB
      13932(T)). It is also proposed that Streptomyces kifunensis should be transferred
      to the genus Kitasatospora as Kitasatospora kifunensis comb. nov. An emended
      description of Streptomyces aureofaciens Duggar 1948 is also given.

PMID- 14657142
TI  - Reclassification of Subtercola pratensis Behrendt et al. 2002 as Agreia pratensis
      comb. nov.
AB  - Comparative analysis of 16S rDNA sequences revealed a close phylogenetic
      relationship (99.6 % similarity) between Subtercola pratensis Behrendt et al.
      2002 and Agreia bicolorata Evtushenko et al. 2001. The two species were found to
      share genus-specific chemotaxonomic characteristics such as the occurrence of D
      ornithine and L-2,4-diaminobutyric acid in the peptidoglycan and the profile of
      cellular fatty acids and 1,1-dimethoxy-alkanes. DNA-DNA relatedness of only 47.8
      % and differences in phenotypic features such as the menaquinone profile and
      oxidase and Voges-Proskauer reactions confirmed the distinct species status of S.
      pratensis and A. bicolorata. On the basis of the data from phylogenetic and
      phenotypic analyses, the reclassification of S. pratensis as Agreia pratensis
      comb. nov. is proposed. As a result of this reclassification, the two genera are
      coherent, in that the cell wall composition and 1,1-dimethoxy-alkane spectrum are
      significant genus-specific characteristics.

PMID- 14657143
TI  - Sphingobium amiense sp. nov., a novel nonylphenol-degrading bacterium isolated
      from a river sediment.
AB  - A nonylphenol-degrading bacterial strain (YT(T)) was isolated previously from a
      river sediment sample obtained in Ami-machi, Ibaraki, Japan, and identified as a
      Sphingomonas species. In this study, the taxonomic relationship between strain
      YT(T), a recently described nonylphenol-degrading strain, Sphingomonas cloacae,
      and Sphingobium yanoikuyae, which is phylogenetically related, was examined.
      Their phenotypic characteristics were compared and levels of DNA-DNA relatedness
      between these strains were determined. Based on the results of physiological and
      biochemical tests and DNA-DNA hybridization, it is proposed that strain YT(T)
      (=IAM 15006(T)=JCM 11777(T)=CIP 107839(T)) represents a novel species of the
      genus Sphingobium, Sphingobium amiense sp. nov.

PMID- 14657144
TI  - Streptomyces luridiscabiei sp. nov., Streptomyces puniciscabiei sp. nov. and
      Streptomyces niveiscabiei sp. nov., which cause potato common scab disease in
      Korea.
AB  - Three plant-pathogenic isolates of Streptomyces spp., isolated from potatoes with
      common scab disease lesions in Korea, are described as novel species.
      Morphological and physiological properties of these isolates were distinct from
      those of previously described Streptomyces species. Strain S63(T) has yellow
      white, smooth, cylindrical spores that are borne in monoverticillus flexuous
      spore-chains. Strain S77(T) has purple-red, spiny spores that are borne in simple
      rectus flexuous spore-chains. Strain S78(T) has white, smooth, cylindrical spores
      that are borne in simple rectus flexuous spore-chains. These three isolates
      differed from known pathogenic strains by analysis of 16S rRNA gene sequences in
      a previous study. Furthermore, genetic uniqueness of our isolates was confirmed
      by sequencing of the 16S-23S internal transcribed spacer (ITS) region, which
      indicated that isolates S63(T) and S78(T) belong to the genus Streptomyces and
      have low homology to other Streptomyces species (less than 71.2 and 75.7 %,
      respectively). The 16S-23S ITS region of strain S77(T) was not amplified by these
      primer sets. DNA-DNA hybridization results for all three isolates show distant
      relationships to previously described Streptomyces species; therefore, on the
      basis of polyphasic evidence, the names Streptomyces luridiscabiei sp. nov. for
      strain S63(T) (=LMG 21390(T)=KACC 20252(T)), Streptomyces puniciscabiei sp. nov.
      for strain S77(T) (=LMG 21391(T)=KACC 20253(T)) and Streptomyces niveiscabiei sp.
      nov. for strain S78(T) (=LMG 21392(T)=KACC 20254(T)) are proposed.

PMID- 14657145
TI  - Lactobacillus kitasatonis sp. nov., from chicken intestine.
AB  - Four strains isolated from chicken small intestine and strains JCM 1038 and JCM
      1039 (designated as Lactobacillus acidophilus) were characterized by phenotypic
      and molecular taxonomic methods. They were Gram-positive, catalase-negative,
      facultatively anaerobic rods that did not produce gas from glucose. These strains
      had similar phenotypic characteristics and exhibited intergroup DNA relatedness
      values of >77 %, indicating that they comprised a single species. The 16S rRNA
      gene sequence of a representative strain, JCM 1039(T) (designated as type strain
      in this study), was determined and aligned with those of other Lactobacillus
      species. JCM 1039(T) was placed in the Lactobacillus delbrueckii cluster of the
      genus Lactobacillus on the basis of phylogenetic analysis and formed an
      independent cluster that was distinct from its closest neighbours, Lactobacillus
      amylovorus, Lactobacillus crispatus, Lactobacillus gallinarum, L. acidophilus and
      Lactobacillus helveticus. Results of DNA-DNA hybridization experiments and whole
      cell protein profiles clearly indicated that these strains represent a novel
      Lactobacillus species, for which the name Lactobacillus kitasatonis sp. nov. is
      proposed; the type strain of this species is JCM 1039(T).

PMID- 14657146
TI  - Salinibacterium amurskyense gen. nov., sp. nov., a novel genus of the family
      Microbacteriaceae from the marine environment.
AB  - Three bacterial strains were isolated from sea-water samples taken from Amursky
      Bay of the Gulf of Peter the Great, East Sea. The isolates, designated KMM 3670,
      KMM 3673(T) and KMM 3928, were Gram-positive, non-motile, aerobic, non-spore
      forming, irregular, rod-shaped actinobacteria. They grew well at mesophilic
      temperatures and neutral pH and tolerated up to 10 % NaCl, although salt was not
      essential for growth. The three strains shared all morphological properties and
      most physiological characteristics tested. Based on subsequent chemotaxonomic and
      phylogenetic analyses, it was evident that the strains represented a distinctive
      taxon in the family Microbacteriaceae. The strains contained a major amount of
      menaquinone with 11 isoprene units; lysine and ornithine were the major cell-wall
      diamino acids. In 16S rDNA analysis, the three strains formed an independent
      phylogenetic lineage within the tree encompassed by members of the family
      Microbacteriaceae. It is notable that the tested strains form the first described
      taxon of Microbacteriaceae that inhabits a marine aquatic environment. The three
      strains evidently merit recognition as a single species of a novel genus in the
      family Microbacteriaceae, for which the name Salinibacterium amurskyense gen.
      nov., sp. nov. (type strain, KMM 3673(T)=KCTC 9931(T)) is proposed.

PMID- 14657147
TI  - Pseudomonas rhizosphaerae sp. nov., a novel species that actively solubilizes
      phosphate in vitro.
AB  - A bacterial strain (designated IH5(T)), isolated from rhizospheric soil of
      grasses growing spontaneously in Spanish soil, actively solubilized phosphates in
      vitro when bicalcium phosphate was used as a phosphorus source. This strain was
      Gram-negative, strictly aerobic, rod-shaped and motile. The strain produced
      catalase, but not oxidase. Cellulose, casein, starch, gelatin, aesculin and urea
      were not hydrolysed. Growth was observed with many carbohydrates as the carbon
      source. The main non-polar fatty acids detected were hexadecenoic acid (C(16 :
      1)), hexadecanoic acid (C(16 : 0)) and octadecenoic acid (C(18 : 1)). The hydroxy
      fatty acids detected were 3-hydroxydecanoic acid (C(10 : 0) 3-OH), 3
      hydroxydodecanoic acid (C(12 : 0) 3-OH) and 2-hydroxydodecanoic acid (C(12 : 0) 2
      OH). Phylogenetic analysis of 16S rRNA indicated that this bacterium belongs to
      the genus Pseudomonas in the gamma-subclass of the Proteobacteria and that the
      closest related species is Pseudomonas graminis. The DNA G+C content was 61 mol%.
      DNA-DNA hybridization showed 23 % relatedness between strain IH5(T) and P.
      graminis DSM 11363(T). Therefore, strain IH5(T) belongs to a novel species from
      the genus Pseudomonas, for which the name Pseudomonas rhizosphaerae sp. nov. is
      proposed (type strain, IH5(T)=LMG 21640(T)=CECT 5726(T)).

PMID- 14657148
TI  - Marinobacter excellens sp. nov., isolated from sediments of the Sea of Japan.
AB  - Five strains of halophilic, Gram-negative marine bacteria (KMM 3809(T), KMM 3814,
      KMM 3815, KMM 3817 and KMM 3818) were isolated from sediments collected from
      Chazhma Bay, Sea of Japan. Phylogenetic 16S rRNA gene sequence-based analysis
      placed these bacteria in a clade within the genus Marinobacter in the gamma
      Proteobacteria. KMM 3809(T) showed highest 16S rRNA gene sequence similarity of
      97.3 % to Marinobacter litoralis and 96.9 % to Marinobacter hydrocarbonoclasticus
      and Marinobacter aquaeolei. DNA-DNA hybridization between the five isolates was
      at the conspecific level (94-96 %) and that among the closest phylogenetic
      neighbours ranged from 45.0 to 62.5 %. The new organisms were susceptible to
      polymyxin. Predominant fatty acids were C(16 : 0), C(16 : 1)omega9c, C(16 :
      1)omega7c and C(18 : 1)omega9c. Phylogenetic evidence, along with phenotypic and
      genotypic characteristics, showed that the bacteria constituted a novel species
      of the genus Marinobacter. The name Marinobacter excellens sp. nov. is proposed
      for this species, with the type strain KMM 3809(T) (=CIP 107686(T)).

PMID- 14657149
TI  - Candida zemplinina sp. nov., an osmotolerant and psychrotolerant yeast that
      ferments sweet botrytized wines.
AB  - Four yeast strains isolated from fermenting botrytized grape musts in the Tokaj
      wine region of Hungary are shown to represent a new osmotolerant and
      psychrotolerant species. The new species, Candida zemplinina (type strain 10
      372(T)=CBS 9494(T)=NCAIM Y016667(T)), is closely related to Candida stellata, a
      yeast common on overripe grapes and in sweet fermenting wines. The sequence of
      the D1/D2 domain of the C. zemplinina 10-372(T) 26S rDNA shows 8.1 % sequence
      difference when compared to its counterpart in C. stellata CBS 157(T). In the
      conserved 5.8S gene of the ITS1-5.8S-ITS2 region the difference is 8 %. The D1/D2
      domain differs only at two nucleotides from the homologous sequence of a yeast
      strain isolated from botrytized grapes in California, suggesting that C.
      zemplinina is a wine yeast that occurs in geographically distant localities.

PMID- 14657150
TI  - Bensingtonia changbaiensis sp. nov. and Bensingtonia sorbi sp. nov., novel
      ballistoconidium-forming yeast species from plant leaves.
AB  - Six ballistoconidium-forming yeast strains that were isolated from plant leaves
      collected on Changbai Mountain, north-east China, were assigned to the genus
      Bensingtonia Ingold emend. Nakase & Boekhout due to the formation of asymmetrical
      ballistoconidia, cream-coloured colonies and Q-9 as the major ubiquinone. Two
      separate groups, representing two novel Bensingtonia species, were recognized
      among these yeasts by 26S rDNA D1/D2 domain, internal transcribed spacer (ITS)
      region and 18S rDNA sequence analyses. The names Bensingtonia changbaiensis sp.
      nov. (type strain, CB 346(T)=AS 2.2310(T)=CBS 9497(T)) and Bensingtonia sorbi sp.
      nov. (type strain, CB 286(T)=AS 2.2303(T)=CBS 9498(T)) are proposed for these two
      species.

PMID- 14657151
TI  - Sporobolomyces bannaensis, a novel ballistoconidium-forming yeast species in the
      Sporidiobolus lineage.
AB  - Among ballistoconidium-forming yeast strains isolated from various plant leaves
      collected in Banna, Yunnan Province, China, five strains that formed pink
      coloured colonies and asymmetric ballistoconidia were classified in a single
      group and assigned to the genus Sporobolomyces by conventional and chemotaxonomic
      studies. Analyses of the internal transcribed spacer region and 26S rDNA D1/D2
      domain sequences indicated that these strains represent a novel species with a
      close phylogenetic relationship to Sporobolomyces blumeae in the Sporidiobolus
      lineage, for which the name Sporobolomyces bannaensis sp. nov. is proposed (type
      strain Y41(T)=AS 2.2285(T)=CBS 9204(T)).

PMID- 14657152
TI  - Cryptococcus surugaensis sp. nov., a novel yeast species from sediment collected
      on the deep-sea floor of Suruga Bay.
AB  - A novel species of the genus Cryptococcus was isolated from sediment collected on
      the deep-sea floor of Suruga Bay, Japan. Nucleotide sequences of 18S rDNA,
      internal transcribed spacers, 5.8S rDNA and the D1/D2 region of 26S rDNA of
      strain SY-260(T) suggested affinities to a phylogenetic lineage that includes
      Cryptococcus luteolus. Comparisons of the rDNA sequences of each region clarified
      that strain SY-260(T) is related distantly to Bullera coprosmaensis and Bullera
      oryzae, but is distinct at the species level. As ballistoconidia and sexual
      reproduction were not observed in strain SY-260(T), this strain is described as
      Cryptococcus surugaensis sp. nov. (type strain, SY-260(T)=JCM 11903(T)=CBS
      9426(T)).

PMID- 14657153
TI  - Phylogenetic affinities of the Trentepohliales inferred from small-subunit rDNA.
AB  - Phylogenetic analyses of the nuclear-encoded small-subunit rDNA sequences from
      taxa representing all of the major lineages of green algae, including new
      sequences for the Trentepohliales, consistently indicated that the subaerial
      Trentepohliales are closely related to ulvophycean marine green algae,
      particularly to the siphonous and hemisiphonous orders. The presence of
      phragmoplast-type cytokinesis in the order Trentepohliales remains enigmatic, and
      it is interesting that this type of cell division is associated with terrestrial
      (subaerial) habits.

PMID- 14657154
TI  - The genus name Ensifer Casida 1982 takes priority over Sinorhizobium Chen et al.
      1988, and Sinorhizobium morelense Wang et al. 2002 is a later synonym of Ensifer
      adhaerens Casida 1982. Is the combination "Sinorhizobium adhaerens" (Casida 1982)
      Willems et al. 2003 legitimate? Request for an Opinion.
AB  - The synonymy of the genera Ensifer and Sinorhizobium was recently reported, but
      it was proposed that the later-named genus, Sinorhizobium, take priority in
      nomenclature. There is no justification in the International Code of Nomenclature
      of Bacteria (Prokaryotes) for this step; Ensifer is the correct name of the
      genus, with Ensifer adhaerens as the type species. Species previously allocated
      to Sinorhizobium are here proposed as the new combinations Ensifer arboris,
      Ensifer fredii, Ensifer kostiensis, Ensifer kummerowiae, Ensifer medicae, Ensifer
      meliloti, Ensifer saheli, Ensifer terangae and Ensifer xinjiangensis.
      Sinorhizobium morelense was proposed in 2002 [Wang, E. T., Tan, Z. Y., Willems,
      A., Fernandez-Lopez, M., Reinhold-Hurek, B. & Martinez-Romero, E., Int J Syst
      Evol Microbiol 52, 1687-1693, 2002], but a consideration of all published data
      indicate that it is a nitrogen-fixing genomovar and later heterotypic synonym of
      Ensifer adhaerens. A Request for an Opinion is made as to whether or not the
      combination "Sinorhizobium adhaerens" (Casida 1982) Willems et al. 2003 is
      legitimate.

PMID- 14657155
TI  - Proposal to conserve the adjectival form of the specific epithet in the
      reclassification of Bacteroides forsythus Tanner et al. 1986 to the genus
      Tannerella Sakamoto et al. 2002 as Tannerella forsythia corrig., gen. nov., comb.
      nov. Request for an Opinion.
AB  - With reference to the first Principle of the International Code of Nomenclature
      of Bacteria, which emphasizes stability of names, it is proposed that the
      original adjectival form of the specific epithet be conserved in the
      reclassification of Bacteroides forsythus to the new genus Tannerella. Thus,
      Tannerella forsythensis Sakamoto et al. 2002 should be Tannerella forsythia
      Sakamoto et al. 2002 corrig., gen. nov., comb. nov., and we put forward a Request
      for an Opinion to the Judicial Commission regarding this correction.

PMID- 14657156
TI  - Enriched environment confers resistance to 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine and cocaine: involvement of dopamine transporter and trophic
      factors.
AB  - We investigated, in mice, the influence of life experience on the vulnerability
      to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a major neurotoxin that
      induces a Parkinson's disease-like syndrome in humans, and to cocaine, a potent
      psychostimulant that promotes drug addiction. Our findings show that adult
      C57BL/6 mice raised in an enriched environment (EE) for only 2 months are
      significantly more resistant to both drugs compared with mice raised in a
      standard environment (SE). Indeed, EE mice showed decreased locomotor activity in
      response to cocaine (10 and 20 mg/kg) as well as a different pattern of c-fos
      expression in the striatum compared with SE mice. After MPTP treatment, SE mice
      showed a 75% loss of dopamine neurons, whereas EE mice showed only a 40% loss.
      The dopamine transporter plays a key role in mediating the effects of both drugs.
      We thus investigated the regulation of its expression. EE mice showed less
      dopamine transporter binding in the striatum and less dopamine transporter mRNA
      per dopamine neuron at the cellular level as demonstrated by in situ
      hybridization. In addition, enriched environment promoted an increase in the
      expression of brain-derived neurotrophic factor in the striatum. These data
      provide a direct demonstration of the beneficial consequences that a positive
      environment has in preventing neurodegeneration and in decreasing responsiveness
      to cocaine. Furthermore, they suggest that the probability of developing
      neurological disorders such as Parkinson's disease or vulnerability to
      psychostimulants may be related to life experience.

PMID- 14657157
TI  - Ca2+ dependency of N-cadherin function probed by laser tweezer and atomic force
      microscopy.
AB  - This study was undertaken to provide a biophysical basis for the hypothesis that
      activity-dependent modulation of cadherin-mediated adhesion by transient changes
      of extracellular calcium ([Ca2+]e) is causally involved in coordination of
      synaptic plasticity. Characterization of homophilic N-cadherin binding by atomic
      force microscopy and laser tweezer trapping of N-cadherin-coated microbeads
      attached to the cell surface of cultured neuronal cells showed that adhesive
      activity of N-cadherin is effectively regulated between 0.3 and 0.8 mm [Ca2+]e.
      Furthermore, we show that an increase of [Ca2+]i, which is known to be essential
      for induction of synaptic plasticity, causes significant reduction of cadherin
      mediated bead adhesion that could be completely suppressed by inhibition of actin
      depolymerization. The results of this study show that N-cadherin has ideal
      biophysical properties to serve as a Ca2+-dependent sensor for synaptic activity
      and, at the same time, is strategically located to control synaptic adhesion. A
      drop of [Ca2+]e and a concomitant increase of [Ca2+]i may act in concert to
      modulate N-cadherin-based adhesive contacts at synaptic sites.

PMID- 14657158
TI  - Mechanisms of caspase-independent neuronal death: energy depletion and free
      radical generation.
AB  - Cultured rat embryonic cortical neurons undergo apoptosis when treated with the
      topoisomerase-I inhibitor camptothecin. Pharmacological or molecular caspase
      inhibition prevents apoptosis, but the neurons still die in a delayed
      nonapoptotic manner. Here we examine the mechanisms leading to such caspase
      independent death, focusing on events related to mitochondrial malfunction, which
      accompanies this delayed death. Given that mitochondria are the major source of
      ATP in primary neurons, we examined the cellular energy state. Mitochondrially
      generated ATP was specifically reduced in neurons treated with camptothecin and
      Boc-aspartyl-fluoromethylketone. Augmentation of cellular ATP by manipulation of
      the glucose content in the cultures led to an increase in survival specifically
      in delayed caspase-independent but not early caspase-dependent death. As another
      possible consequence of mitochondrial malfunction, we found an induction of
      reactive oxygen species in delayed death. The free radical scavenger Tempol, but
      not other classes of antioxidants, reduced oxidative stress and promoted
      survival. Other potential events known to be a direct or indirect consequence of
      mitochondrial dysfunction, such as the induction of autophagy, release of
      apoptosis-inducing factor, or opening of the mitochondrial permeability
      transition pore, were not found to play a significant role in caspase-independent
      neuronal death. Combining the strategies of increasing intracellular ATP and
      reducing free radicals led to an additive increase in neuronal survival. We
      conclude that energy failure and free radical generation contribute to caspase
      independent neuronal death. Both could represent potential targets for
      therapeutic interventions complementary to caspase inhibition.

PMID- 14657159
TI  - Subcellular localization of metabotropic GABA(B) receptor subunits GABA(B1a/b)
      and GABA(B2) in the rat hippocampus.
AB  - Metabotropic GABA(B) receptors mediate slow inhibitory effects presynaptically
      and postsynaptically. Using preembedding immunohistochemical methods combined
      with quantitative analysis of GABA(B) receptor subunit immunoreactivity, this
      study provides a detailed description of the cellular and subcellular
      localization of GABA(B1a/b) and GABA(B2) in the rat hippocampus. At the light
      microscopic level, an overlapping distribution of GABA(B1a/b) and GABA(B2) was
      revealed in the dendritic layers of the hippocampus. In addition, expression of
      the GABA(B1a/b) subunit was found in somata of CA1 pyramidal cells and of a
      subset of GABAergic interneurons. At the electron microscopic level,
      immunoreactivity for both subunits was observed on presynaptic and, more
      abundantly, on postsynaptic elements. Presynaptically, subunits were mainly
      detected in the extrasynaptic membrane and occasionally over the presynaptic
      membrane specialization of putative glutamatergic and, to a lesser extent,
      GABAergic axon terminals. Postsynaptically, the majority of GABA(B) receptor
      subunits were localized to the extrasynaptic plasma membrane of spines and
      dendritic shafts of principal cells and shafts of interneuron dendrites.
      Quantitative analysis revealed enrichment of GABA(B1a/b) around putative
      glutamatergic synapses on spines and an even distribution on dendritic shafts of
      pyramidal cells contacted by GABAergic boutons. The association of GABA(B)
      receptors with glutamatergic synapses at both presynaptic and postsynaptic sides
      indicates their intimate involvement in the modulation of glutamatergic
      neurotransmission. The dominant extrasynaptic localization of GABA(B) receptor
      subunits suggests that their activation is dependent on spillover of GABA
      requiring simultaneous activity of populations of GABAergic cells as it occurs
      during population oscillations or epileptic seizures.

PMID- 14657160
TI  - Neurotrophic effects of vascular endothelial growth factor on organotypic
      cortical explants and primary cortical neurons.
AB  - Vascular endothelial growth factor (VEGF) is well known to play an important
      regulatory role in vascular growth and development. Because gene knock-outs of
      VEGF and its receptors flk-1 and flt-1 result in early embryonic lethality,
      determining roles for VEGF in CNS development has been particularly difficult.
      Recent studies have shown that VEGF is upregulated after various injuries to the
      adult brain and that the cytokine affords protection to cultured neurons affected
      by oxidative or excitotoxic stress. The present study demonstrates, for the first
      time, that VEGF is directly neurotrophic to CNS neurons in culture. We applied
      VEGF to normoxic fetal organotypic cortical explants as a model of CNS neuropil,
      in addition to primary cortical neurons, to assess direct growth effects absent
      vascular or astroglial activity. We found that VEGF provided a significant dose
      responsive increase in the neuronal microtubule markers TUJ1 and MAP-2, as well
      as mRNA for MAP-2 and flk-1. Antisense oligodeoxynucleotides to flk-1, but not
      flt-1, inhibited neuritic outgrowth, whereas inhibitors of the signaling pathways
      MEK1 and P13-AKT both abrogated VEGF-induced growth. VEGF applied to primary
      cortical neurons produced significant increases in neuronal cell body diameter
      and the number of emerging neurites mediated by flk-1. Possibly, VEGF achieves
      its effects by acting on the neuronal microtubular content, which is involved
      with growth, stability and maturation. Several studies have now shown that VEGF
      is neurotrophic and neuroprotective independent of a vascular component; we
      suggest that VEGF plays seminal pleiotrophic roles in CNS development and repair.

PMID- 14657162
TI  - The prefrontal cortex regulates lateral amygdala neuronal plasticity and
      responses to previously conditioned stimuli.
AB  - The amygdala plays a role in learning and memory processes that involve an
      emotional component. However, neural structures that regulate these amygdala
      dependent processes are unknown. Previous studies indicate that regulation of
      affect may be imposed by the prefrontal cortex (PFC) and its efferents to the
      amygdala. The presentation of conditioned affective stimuli enhances activity of
      neurons in the lateral nucleus of the amygdala (LAT), which is thought to drive
      conditioned affective responses. Moreover, plasticity of LAT neuronal responses
      to stimuli during the course of conditioning is believed to underlie affective
      learning. This study examines the role of the PFC in the regulation of affective
      behaviors by evaluating how the PFC affects LAT neuronal plasticity and activity
      that is evoked by previously conditioned stimuli. In vivo intracellular
      recordings were performed from the LAT of anesthetized rats during pavlovian
      conditioning and during the presentation of stimuli that were conditioned in the
      awake rat before recording. Train stimulation of the PFC suppressed LAT neuronal
      activity that was evoked by both previously conditioned and neutral stimuli. In
      addition, PFC stimulation blocked LAT neuronal plasticity associated with an
      affective conditioning procedure. These results indicate that the PFC has the
      potential to regulate affective processes by inhibition of the LAT. Patients with
      disruptions of the PFC-LAT interaction often display an inability to regulate
      affective responses. This may be attributable to the loss of PFC-imposed
      inhibition of the emotional response to a stimulus but may also include the
      formation or diminished extinction of inappropriate associations.

PMID- 14657161
TI  - The beta3 nicotinic receptor subunit: a component of alpha-conotoxin MII-binding
      nicotinic acetylcholine receptors that modulate dopamine release and related
      behaviors.
AB  - Nigrostriatal dopaminergic neurons express many nicotinic acetylcholine receptor
      (nAChR) subunits capable of forming multiple nAChR subtypes. These subtypes are
      expressed differentially along the neuron and presumably mediate diverse
      responses. beta3 subunit mRNA has restricted expression but is abundant in the
      substantia nigra and ventral tegmental areas. To investigate the potential
      role(s) of nicotinic receptors containing the beta3 subunit in dopaminergic
      tracts, we generated mice with a null mutation in the beta3 gene. We were thereby
      able to identify a population of beta3-dependent alpha-conotoxin MII-binding
      nAChRs that modulate striatal dopamine release. Changes were also observed in
      locomotor activity and prepulse inhibition of acoustic startle, behaviors that
      are controlled, in part, by nigrostriatal and mesolimbic dopaminergic activity,
      respectively, suggesting that beta3-containing nAChRs modulate these behaviors.

PMID- 14657163
TI  - A role of Rnd1 GTPase in dendritic spine formation in hippocampal neurons.
AB  - Rho family of small GTPases are key regulators for morphological changes of
      neurons on the basis of reorganization of the actin cytoskeleton. Rnd1, a novel
      member of this family, is predominantly expressed in neurons in brain; however,
      the neuronal functions of Rnd1 are not known. Here we investigated the effect of
      Rnd1 on neuronal morphology. Northern blot analysis of Rnd1 expression in rat
      brain showed that Rnd1 mRNA was highly expressed during early postnatal period,
      the synaptogenic stage. In situ hybridization analysis at this period revealed
      that Rnd1 mRNA was strongly expressed in neurons, including the hippocampal
      pyramidal neurons. Furthermore, immunoblot analysis showed that Rnd1 protein was
      localized in synaptosomal membrane fraction. Ectopical overexpression of Rnd1 in
      cultured rat hippocampal neurons promoted the elongation of dendritic spines. On
      the other hand, suppression of endogenous Rnd1 level by antisense oligonucleotide
      of Rnd1 caused the increase in the percentage of headless protrusions accompanied
      by the reduction in the spine number and spine width and shortened the length of
      the headless protrusions. These results indicate that Rnd1 plays a role in spine
      formation in the developmental synaptogenic stage.

PMID- 14657164
TI  - Cannabinoids decrease corticostriatal synaptic transmission via an effect on
      glutamate uptake.
AB  - Activation of cannabinoid CB1 receptors reduces glutamatergic synaptic
      transmission in the rodent striatum and is involved in the normal control of
      motor function by the basal ganglia. Here we investigated CB1 receptor regulation
      of glutamate release and uptake and synaptic transmission in the rat striatum. We
      show that CB1 receptor activation reduces both the release and uptake of
      [3H]glutamate in striatal slices. We also demonstrate that both activation of CB1
      receptors and inhibition of glutamate uptake reduce corticostriatal synaptic
      transmission in a mutually occlusive manner and that both forms of depression are
      dependent on metabotropic glutamate receptor (mGluR) activation. We propose that
      CB1 receptor activation in the striatum decreases glutamate transporter activity
      and that the resulting increase in synaptic cleft glutamate concentration causes
      the activation of presynaptic mGluRs, which then decrease glutamate release.

PMID- 14657165
TI  - Different roles for orbitofrontal cortex and basolateral amygdala in a reinforcer
      devaluation task.
AB  - The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) are critical for
      using learned representations of outcomes to guide behavior. Neurophysiological
      findings suggest complementary roles in which the BLA acquires associations
      between cues and outcomes and the OFC subsequently uses them to guide behavior.
      Here, we have used a reinforcer devaluation paradigm to test this hypothesis. In
      this paradigm, rats are first trained to associate a light conditioned stimulus
      (CS) with a food outcome, and then the food is devalued by pairing it with
      illness. After this devaluation procedure, responding to the CS is assessed in a
      single probe session. Previously, we have shown that BLA and OFC lesions made
      before training do not affect the acquisition of conditioned responding but do
      impair the sensitivity of that responding to reinforcer devaluation. Rats with
      such lesions fail to exhibit the spontaneous decrease in conditioned responding
      to the light cue observed in controls in the probe test. Here, we have extended
      those findings by showing that performance in the probe test is impaired by OFC
      lesions made after light-food conditioning but not by BLA lesions made after that
      training. These findings indicate that the OFC and BLA play different roles in
      mediating normal goal-directed performance in this, and likely other, settings.
      The BLA seems critical to forming representations linking cues to the incentive
      properties of outcomes but not for maintaining these representations in memory,
      updating them with new information, or for expressing them in behavior. In
      contrast, the OFC seems essential for one or more of these latter processes.

PMID- 14657166
TI  - Activity-dependent feedforward inhibition modulates synaptic transmission in a
      spinal locomotor network.
AB  - The analysis of synaptic properties in neural networks has focused on the
      properties of individual synapses. As a result, little is known of how neural
      assemblies arise from the connectivity and functional properties of different
      classes of network neurons. I examined synaptic properties in the lamprey
      locomotor network. Here I show that, in addition to their monosynaptic inputs to
      motor neurons, a proportion of the excitatory network interneurons (EINs) evoke
      an activity-dependent disynaptic feedforward inhibitory input. Connections from
      the excitatory interneurons to small ipsilateral inhibitory interneurons were
      found that could account for the feedforward inhibition. Both synapses in the
      disynaptic pathway exhibited activity-dependent facilitation during
      physiologically relevant spike trains, which could contribute to the delayed,
      activity-dependent development of the feedforward IPSP. Although it was not as
      common as the feedforward inhibition, the excitatory interneurons could also
      evoke feedforward excitatory inputs in motor neurons. EIN inputs to motor neurons
      usually depress during spike trains. In connections in which a delayed IPSP
      occurred, blocking the feedforward inhibition in motor neurons or preventing the
      activation of the disynaptic pathway abolished the depression of the direct EPSP
      during the spike train and could reveal an underlying facilitation. The
      feedforward inhibition thus heterosynaptically depressed the direct excitatory
      input to motor neurons. Activity-dependent heterosynaptic effects acting within
      network cellular assemblies can thus influence the integration of synaptic inputs
      in motor neurons. This could help to terminate ipsilateral motor neuron spiking
      during network activity.

PMID- 14657167
TI  - Modulation of the innate immune response by NMDA receptors has neuropathological
      consequences.
AB  - The aim of this study was to determine whether glutamate receptors modulate the
      innate immune response in the brain of C3H/HeN and C3H/HeJ mice; the latter bear
      a loss of function in the toll-like receptor (TLR) 4 gene. Mice received an
      intrastriatal (IS) infusion of lipopolysaccharide (LPS), the exogenous ligand for
      TLR4, and were killed at several times thereafter. This treatment activated the
      transcription of a wide variety of genes involved in the control of the innate
      immune response. MK-801, an antagonist of NMDA glutamate receptor subtype,
      exacerbated the effects of the endotoxin in the brain of C3H/HeN mice but not in
      TLR4-deficient animals. The ipsilateral side of C3H/HeN mice exhibited stronger
      hybridization signals for the mRNA encoding TLR2, CD14, tumor necrosis factor
      alpha, and inhibitory factor-kappaBalpha at various times after the treatment
      combining MK-801 and LPS. This robust inflammatory response in the brain of
      C3H/HeN mice was not associated with any convincing signs of neurodegeneration or
      demyelination that was verified via numerous approaches and at time up to 2 weeks
      after injection. However, animals that received long-term IS infusion of LPS,
      together with MK-801, exhibited a significant increase in demyelination levels
      within the ipsilateral side. Our results demonstrate that binding of glutamate to
      its cognate NMDA receptor modulates LPS-induced innate immune reaction in a TLR4
      dependent manner. This acute response may be crucial to eliminate bacterial cell
      wall components and minimizing tissue injury. However, sustained deregulation of
      proinflammatory signaling involving NMDA receptors leads to demyelination and is
      likely to be a mechanism participating in such pathological conditions.

PMID- 14657168
TI  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors protect cortical
      neurons from excitotoxicity.
AB  - 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, reduce
      the incidence of strokes and reduce infarct volume after cerebral ischemia in
      mice. Excitoxicity caused by overstimulation of glutamate receptors is a major
      cause of neuronal death after an ischemic brain insult. Experiments presented
      here explored whether statins protect cultured neurons from excitotoxic death
      caused by the glutamate receptor agonist NMDA. Treatment with statins preserved
      NMDA receptor-expressing cortical neurons and potently and substantially reduced
      lactate dehydrogenase release caused by exposure of embryonic mouse neocortical
      cultures to NMDA. The rank order of neuroprotective potency was rosuvastatin =
      simvastatin > atorvastatin = mevastatin > pravastatin, which is similar to the
      known rank order of potency for inhibition of the HMG-CoA reductase enzyme.
      Resistance of cultures to NMDA excitotoxicity developed after several days of
      statin exposure. Neuroprotection by rosuvastatin was coincident with a decrease
      in cell sterols and occurred with a similar potency as inhibition of cholesterol
      biosynthesis. Neuroprotection was substantially attenuated by cotreatment with
      either mevalonate or cholesterol and was mimicked by acute treatment with the
      cholesterol-extracting agent beta-cyclodextrin, suggesting that neuroprotection
      was mediated by depletion of a cellular pool of cholesterol because of the
      inhibition of cholesterol biosynthesis. These results suggest the possibility
      that, in addition to effects on cerebrovascular function, statins have the
      potential to render cortical neurons more resistant to NMDA-induced excitotoxic
      death as a result of changes in cell cholesterol homeostasis.

PMID- 14657169
TI  - The proapoptotic activities of Bax and Bak limit the size of the neural stem cell
      pool.
AB  - The proapoptotic Bcl-2 family members Bak and Bax play central and redundant
      roles in the regulation of apoptosis. In this study, we investigated the effect
      of loss of Bax and Bak in the CNS. The adult bax-/-bak-/- mice display masses of
      densely staining cells in the proliferative zones of the brain. These cells are
      shown to be a mix of neural progenitor cells and postmitotic cells at different
      stages of neural and glial differentiation. Both neural progenitor cells and
      mature neurons derived from bax-/-bak-/- mice were resistant to various apoptotic
      stimuli. Despite this resistance, postmitotic mature bax-/-bak-/- neurons remain
      as sensitive to excitoxic death as wild-type neurons. Thus, Bax and Bak play a
      critical role in regulating the number of neural progenitor cells in the adult
      brain but are not absolutely required for the initiation of neuronal cell death
      after neurotoxic injury.

PMID- 14657170
TI  - Analgesia induced by dietary restriction is mediated by the kappa-opioid system.
AB  - Progress in the control and treatment of pain may be facilitated by a better
      understanding of mechanisms underlying nociceptive processing. Here we show that
      mice subjected to an intermittent fasting diet (IFD) display markedly reduced
      responses in models of thermal and visceral pain compared with mice fed ad
      libitum (AL). Pharmacological analyses suggest that a change in the endogenous
      kappa-opioid system underlies IFD-induced analgesia. The levels of prodynorphin
      mRNA and kappa-opioid receptors in the spinal cord are higher in IFD than in AL
      mice. Furthermore, in spinal cord nuclear protein extracts, the activity of the
      transcriptional repressor DREAM (downstream regulatory element antagonist
      modulator), the main regulator of prodynorphin expression, is lower in IFD than
      in AL mice. Finally, c-Fos expression in dorsal spinal cord after noxious
      stimulation is significantly lower in IFD than in AL animals, indicating that
      dynorphin could block nociceptive information at the spinal cord. These results
      suggest that dietary restriction together with administration of kappa-opioid
      agonists could be useful as a new therapeutic approach for pain relief.

PMID- 14657171
TI  - Matrix metalloproteinase-9 facilitates remyelination in part by processing the
      inhibitory NG2 proteoglycan.
AB  - Remyelination is a critical repair process that is initiated after a
      demyelinating insult. The failure to remyelinate contributes to neurological
      diseases such as multiple sclerosis. Here, we test the hypothesis that proteinase
      activity is required for the extensive remodeling of the extracellular matrix
      that occurs during remyelination. We show that mice lacking matrix
      metalloproteinase (MMP)-9 are impaired in myelin reformation after lysolecithin
      induced demyelination. This deficiency may be explained at least in part by the
      failure to clear the accumulation of NG2, an inhibitory proteoglycan that retards
      the maturation and differentiation of oligodendrocytes that are needed for
      remyelination. These results emphasize for the first time that upregulation of
      MMP activity can be important for facilitating regeneration from some types of
      CNS injury.

PMID- 14657172
TI  - Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively
      overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains.
AB  - The endocannabinoid system is still poorly understood. Recently, the basic
      elements that constitute it, i.e., membrane receptors, endogenous ligands, and
      mechanisms for termination of the signaling process, have been partially
      characterized. There is a considerable lack of information, however, concerning
      the distribution, concentration, and function of those components in the human
      body, particularly during pathological events. We have studied the status of some
      of the components of the endocannabinoid system, fatty acid amide hydrolase and
      cannabinoid CB1 and CB2 receptors, in postmortem brains from patients with
      Alzheimer's disease. Using specific polyclonal antibodies, we have performed
      immunohistochemical analysis in hippocampus and entorhinal cortex sections from
      brains of Alzheimer's disease patients. Our results show that both fatty acid
      amide hydrolase and cannabinoid CB2 receptors are abundantly and selectively
      expressed in neuritic plaque-associated astrocytes and microglia, respectively,
      whereas the expression of CB1 receptors remains unchanged. In addition, the
      hydrolase activity seems to be elevated in the plaques and surrounding areas.
      Thus, some elements of the endocannabinoid system may be postulated as possible
      modulators of the inflammatory response associated with this neurodegenerative
      process and as possible targets for new therapeutic approaches.

PMID- 14657173
TI  - Maturation of long-term potentiation induction rules in rodent hippocampus: role
      of GABAergic inhibition.
AB  - The induction rules of synaptic plasticity are important for the functional
      operation of a neural network. We asked whether such synaptic plasticity rules
      change during development from juvenile to adult animals. Using perforated patch
      and whole-cell recordings from CA1 pyramidal cells in hippocampal slices, we
      demonstrate here that the postsynaptic requirements for induction of associative
      long-term potentiation (LTP) shift gradually. Presynaptic stimulation paired with
      single postsynaptic action potentials became progressively less effective at
      inducing LTP with advancing developmental age until, in adult hippocampus,
      postsynaptic bursts of action potentials were necessary to induce synaptic
      potentiation. This developmental change might be accounted for by changes in
      GABA(A) receptor-mediated inhibition known to occur in the hippocampus during
      this postnatal period, because blocking GABA(A) receptor-mediated inhibition re
      established the effectiveness of single postsynaptic action potentials at
      inducing LTP in adult hippocampus. These data reveal a gradual shift in the
      induction rules for LTP, explained by a maturational change in GABAergic
      inhibition, and could have implications for our understanding of the role of
      inhibition in information processing in the brain.

PMID- 14657174
TI  - Physiology of cells in the central lobes of the mormyrid cerebellum.
AB  - The cerebellum of mormyrid electric fish is unusual for its size and for the
      regularity of its histology. The circuitry of the mormyrid cerebellum is also
      different from that of the mammalian cerebellum in that mormyrid Purkinje cell
      axons terminate locally within the cortex on efferent cells, and the cellular
      regions of termination for climbing fibers and parallel fibers are well
      separated. These and other features suggest that the mormyrid cerebellum may be a
      useful site for addressing some functional issues regarding cerebellar circuitry.
      We have therefore begun to examine the physiology of the mormyrid cerebellum by
      recording intracellularly from morphologically identified Purkinje cells,
      efferent cells, Golgi cells, and stellate cells in in vitro slices. Mormyrid
      Purkinje cells respond to parallel fiber input with an AMPA-mediated EPSP that
      shows paired pulse facilitation and to climbing fiber input with a large all-or
      none AMPA-mediated EPSP that shows paired pulse depression. Recordings from the
      somas of Purkinje cells show three types of spikes in response to injected
      current: a small, narrow sodium spike; a large, broad sodium spike; and a large
      broad calcium spike. Efferent cells, Golgi cells, and stellate cells respond to
      parallel fiber input with an EPSP or EPSP-IPSP sequence and show only large,
      narrow spikes in response to intracellular current injection. We conclude that
      the physiology of the mormyrid cerebellum is similar in many ways to the
      mammalian cerebellum but is also different in ways that may prove instructive
      concerning the functional circuitry of the cerebellum.

PMID- 14657175
TI  - Individual properties of the two functional agonist sites in GABA(A) receptors.
AB  - The members of the pentameric ligand-gated receptor channel family are involved
      in information transfer in synapses and the neuromuscular junction. They often
      contain several copies of the same subunit isoform. Here, we present a method to
      functionally dissect the role of individual subunits that occur in multiple
      copies in these receptors. Opening of the inherent chloride channel in the
      GABA(A) receptor is achieved through the binding of two agonist molecules;
      however, it has been difficult to obtain information on the contribution of the
      two individual binding sites. The sites are both located at beta+/alpha- subunit
      interfaces, suggesting similar properties. One pair of subunits is flanked by
      gamma and beta (site 1) and the other by alpha and gamma (site 2), the different
      environment possibly affecting the binding sites. Here, we used concatenated
      subunits and two point mutations of amino acid residues, each in alpha and beta
      subunits, both located in the agonist binding pocket, to investigate the
      properties of these two sites. The sites were individually mutated, and
      consequences of these mutations on GABA and muscimol-induced channel opening and
      its competitive inhibition by bicuculline were studied. A model predicts that
      opening also occurs for receptors occupied with a single agonist molecule but is
      promoted approximately 60-fold in those occupied by two agonists and that site 2
      has an approximately threefold higher affinity for GABA than site 1, whereas
      muscimol and bicuculline show some preference for site 1.

PMID- 14657176
TI  - Neuronal avalanches in neocortical circuits.
AB  - Networks of living neurons exhibit diverse patterns of activity, including
      oscillations, synchrony, and waves. Recent work in physics has shown yet another
      mode of activity in systems composed of many nonlinear units interacting locally.
      For example, avalanches, earthquakes, and forest fires all propagate in systems
      organized into a critical state in which event sizes show no characteristic scale
      and are described by power laws. We hypothesized that a similar mode of activity
      with complex emergent properties could exist in networks of cortical neurons. We
      investigated this issue in mature organotypic cultures and acute slices of rat
      cortex by recording spontaneous local field potentials continuously using a 60
      channel multielectrode array. Here, we show that propagation of spontaneous
      activity in cortical networks is described by equations that govern avalanches.
      As predicted by theory for a critical branching process, the propagation obeys a
      power law with an exponent of -3/2 for event sizes, with a branching parameter
      close to the critical value of 1. Simulations show that a branching parameter at
      this value optimizes information transmission in feedforward networks, while
      preventing runaway network excitation. Our findings suggest that "neuronal
      avalanches" may be a generic property of cortical networks, and represent a mode
      of activity that differs profoundly from oscillatory, synchronized, or wave-like
      network states. In the critical state, the network may satisfy the competing
      demands of information transmission and network stability.

PMID- 14657177
TI  - Genetic control of interconnected neuronal populations in the mouse primary
      visual system.
AB  - Proliferation and survival of different cell types is thought to be modulated by
      cell interactions during development that achieve numerical and functional
      balance. We tested the precision of coregulation of numbers of neurons, glial
      cells, and endothelial cells in the dorsal lateral geniculate nucleus (LGN) in 58
      isogenic strains of mice. We acquired matched counts of retinal ganglion cells
      (RGCs) in these strains and tested the precision of numerical matching between
      retina and LGN. Cells were counted using unbiased counting protocols and tissue
      from the Mouse Brain Library (www.mbl.org). Classification criteria were assessed
      using immunohistochemical criteria. The LGN contains an average of 17,000
      neurons, 12,000 glial cells, and 10,000 endothelial cells. Variation around these
      means is typically twofold, and cell ratios vary widely. Strain differences in
      LGN volume correlate moderately well with glial cell number (r = 0.69) and less
      well with RGC number (r = 0.35) and with LGN neuron number (r = 0.32).
      Populations of LGN neurons and glial cells correlate only modestly (r = 0.44; p <
      0.01). The single most surprising and unequivocal finding was the lack of any
      detectable correlation between populations of LGN neurons and RGCs, a correlation
      of merely 0.01 across 56 strains. In contrast, RGC number correlates
      significantly with LGN glial cell number, a surprising twist on the numerical
      matching hypothesis (r = 0.33; p < 0.01). We conclude that numbers of these two
      functionally coupled neuron populations are modulated over a wide range by
      independent genetic and developmental mechanisms.

PMID- 14657178
TI  - Lesions of the orbitofrontal but not medial prefrontal cortex disrupt conditioned
      reinforcement in primates.
AB  - The ventromedial prefrontal cortex (PFC) is implicated in affective and motivated
      behaviors. Damage to this region, which includes the orbitofrontal cortex as well
      as ventral sectors of medial PFC, causes profound changes in emotional and social
      behavior, including impairments in certain aspects of decision making. One
      reinforcement mechanism that may well contribute to these behaviors is
      conditioned reinforcement, whereby previously neutral stimuli in the environment,
      by virtue of their association with primary rewards, take on reinforcing value
      and come to support instrumental action. Conditioned reinforcers are powerful
      determinants of behavior and can maintain responding over protracted periods of
      time in the absence of and potentially in conflict with primary reinforcers. It
      has already been shown that conditioned reinforcement is dependent on the
      amygdala, and because the amygdala projects to both the orbitofrontal cortex and
      the medial PFC, the present study determined whether conditioned reinforcement
      was also dependent on one or the other of these prefrontal regions. Comparison of
      the behavioral effects of selective excitotoxic lesions of the PFC in the common
      marmoset revealed that orbitofrontal but not medial PFC lesions disrupted two
      distinct measures of conditioned reinforcement: (1) acquisition of a new response
      and (2) sensitivity to conditioned stimulus omission on a second-order schedule.
      In contrast, the orbitofrontal lesion did not affect sensitivity to primary
      reinforcement as measured by responding on a progressive-ratio schedule and a
      home cage consumption test. Together, these findings demonstrate the critical and
      specific involvement of the orbitofrontal cortex but not the medial PFC in
      conditioned reinforcement.

PMID- 14657180
TI  - Selective encoding of cocaine versus natural rewards by nucleus accumbens neurons
      is not related to chronic drug exposure.
AB  - We reported previously that subsets of nucleus accumbens (Acb) neurons
      differentially encode information about goal-directed behaviors for "natural"
      (food and water) versus cocaine reward in animals well trained to self-administer
      the drug (Carelli et al., 2000). Here, we examined whether repeated exposure to
      cocaine is the crucial determinate of the selective encoding of cocaine versus
      water reinforcement by Acb neurons. Acb cells were recorded during a water
      cocaine multiple schedule from the first day of cocaine exposure as well as
      during repeated sessions. Specifically, animals were initially trained to press a
      lever for water and were then surgically prepared for extracellular recording in
      the Acb. After 1 week, Acb cells were recorded during acquisition of the water
      cocaine multiple schedule. Because behavioral responding for water was already
      established, training on the multiple schedule was divided into three components
      corresponding to acquisition of self-administration: (1) "initial" (day 1 of self
      administration), (2) "reliable" (self-administration behavior was present but
      erratic), and (3) "stable" (cocaine responding was stable). During the initial
      component, the percentage of water-selective neurons was high compared with
      cocaine neurons. However, this became approximately equal with repeated self
      administration experience (i.e., during the stable component). Remarkably, the
      percentage of neurons showing overlapping (similar) neuronal firing patterns
      during initial exposure to cocaine was low (<8%) and remained low during reliable
      and stable components. These findings support the view that separate neural
      circuits in the Acb differentially encode information about cocaine versus
      natural reward, and that this functional organization is not a direct consequence
      of chronic drug exposure.

PMID- 14657179
TI  - Circadian gene expression regulates pulsatile gonadotropin-releasing hormone
      (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.
AB  - Although it has long been established that episodic secretion of gonadotropin
      releasing hormone (GnRH) from the hypothalamus is required for normal
      gonadotropin release, the molecular and cellular mechanisms underlying the
      synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse
      hypothalamic cell line as a model for GnRH secretion, because these cells release
      GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible
      molecular mechanisms governing secretory timing, we investigated the role of the
      molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express
      many known core circadian clock genes, and we demonstrate that oscillations of
      these components can be induced by stimuli such as serum and the adenylyl cyclase
      activator forskolin, similar to effects observed in fibroblasts. Strikingly,
      perturbation of circadian clock function in GT1-7 cells by transient expression
      of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of
      GnRH secretion, significantly decreasing mean pulse frequency. Additionally,
      overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially
      increases GnRH pulse amplitude without a commensurate change in pulse frequency,
      demonstrating that an endogenous biological clock is coupled to the mechanism of
      neurosecretion in these cells and can regulate multiple secretory parameters.
      Finally, mice harboring a somatic mutation in the Clock gene are subfertile and
      exhibit a substantial increase in estrous cycle duration as revealed by
      examination of vaginal cytology. This effect persists in normal light/dark (LD)
      cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in
      GnRH neurons is required for eliciting normal pulsatile patterns of GnRH
      secretion.

PMID- 14657182
TI  - Presynaptic ryanodine-sensitive calcium stores contribute to evoked
      neurotransmitter release at the basket cell-Purkinje cell synapse.
AB  - Presynaptic terminals of cerebellar basket cells are known to contain ryanodine
      sensitive calcium stores (RyCSs); recently, it has been shown that these stores
      control the frequency of miniature synaptic currents in the absence of
      presynaptic spiking. Here, using paired recordings of basket cell-Purkinje cell
      synapses, we show that blocking the RyCSs with high concentration of ryanodine
      decreases the mean amplitude of evoked IPSCs to 70% of the control value. The
      paired-pulse ratio and failure rate increase, indicating that the reduction stems
      from a decreased probability of evoked neurotransmitter release. Various control
      experiments eliminate the possibility of an indirect effect of ryanodine via
      activation of postsynaptic receptors. Prolonged application of cyclopiazonic
      acid, a blocker of the endoplasmic reticulum calcium pump, totally abolishes the
      ryanodine action. Our results indicate that calcium released from presynaptic
      RyCSs enhances the amplitude of evoked GABAergic synaptic currents. The precise
      mechanism by which calcium released from internal stores affect action potential
      dependent release is unknown; however, our results suggest that these stores do
      not provide additional calcium for each presynaptic action potential; rather,
      they appear to enhance depolarization-induced calcium signals indirectly, perhaps
      by increasing the basal level of cytosolic calcium concentration in the vicinity
      of release sites.

PMID- 14657181
TI  - Angiotensin II blocks nicotine-mediated neuroprotection against beta-amyloid (1
      42) via activation of the tyrosine phosphatase SHP-1.
AB  - We showed recently that nicotine activates the growth-promoting enzyme Janus
      kinase 2 (JAK2) in PC12 cells and that preincubation of these cells with the JAK2
      specific inhibitor AG-490 blocked the nicotine-induced neuroprotection against
      beta-amyloid (1-42) [Abeta (1-42)]. These results provided direct evidence for
      linkage between JAK2 and the alpha7 nicotinic acetylcholine receptor-induced
      neuroprotection in PC12 cells. We also showed that preincubation with angiotensin
      II (Ang II), functioning via the angiotensin II type 2 (AT2) receptor, blocked
      both the nicotine-induced activation of JAK2 and its neuroprotection against
      Abeta (1-42). Recently growth-inhibitory effects of the AT2 receptor have been
      reported to be mediated by the activation of protein tyrosine phosphatases
      (PTPases) and that AT2 receptor stimulation is associated with a rapid activation
      of the PTPase SHP-1 (the cytoplasmic tyrosine phosphatase that contains Src
      homology 2 domains), a negative regulator of JAK2 signaling. Therefore, the
      potential biological significance of AT2 receptor-induced effects on both the
      nicotine-induced activation of JAK2 and its neuroprotection against Abeta (1-42)
      led us to investigate whether SHP-1 activation could be involved in this process.
      We found that Ang II induced the activation of SHP-1 and that an antisense
      against SHP-1 not only augmented the nicotine-induced tyrosine phosphorylation of
      JAK2 but also blocked the Ang II neutralization of the nicotine-induced
      neuroprotection. These results demonstrate that nicotine-induced tyrosine
      phosphorylation of JAK2 and neuroprotection against Abeta (1-42) in PC12 cells
      are blocked by Ang II via AT2 receptor-induced activation of SHP-1.

PMID- 14657183
TI  - Control of secretion by temporal patterns of action potentials in adrenal
      chromaffin cells.
AB  - Action potentials (APs) are the principal physiological stimuli for
      neurotransmitter secretion in neurons. Most studies on stimulus-secretion
      coupling have been performed under voltage clamp using artificial electrical
      stimuli. To investigate the modulatory effects of AP codes on neural secretion,
      we introduce a capacitance method to study AP-induced secretion in single cells.
      The action potential pattern was defined by a four-parameter "code function:"
      F(n, m, f, d). With this method, cell secretion evoked by stimulation with an AP
      code was quantified in real time by membrane capacitance (Cm) in adrenal
      chromaffin cells. We found, in addition to AP frequency (f), for a given number
      of APs, another parameter of the AP code, the number of AP bursts (m) in which
      the set of APs occurs, can effectively modulate cell secretion. Possible
      mechanisms of the m effect are depletion of the readily releasable pool and
      inactivation of Ca2+ channels during a burst of APs. The physiological m effect
      may play a key role in AP-mediated neural information transfer within a single
      neuron and among the elements of a neural network.

PMID- 14657184
TI  - Developmental decrease in NMDA receptor desensitization associated with shift to
      synapse and interaction with postsynaptic density-95.
AB  - NMDA receptors (NMDARs) play a crucial role in neuronal development, synaptic
      plasticity, and excitotoxicity; therefore, regulation of NMDAR function is
      important in both physiological and pathological conditions. Previous studies
      indicate that the NMDAR-mediated synaptic current decay rate increases during
      development because of a switch in receptor subunit composition, contributing to
      developmental changes in plasticity. To test whether NMDAR desensitization also
      changes during development, we recorded whole-cell NMDA-evoked currents in
      cultured rat hippocampal neurons. We found that glycine-independent
      desensitization of NMDARs decreases during development. This decrease was not
      dependent on a switch in subunit composition or differential receptor sensitivity
      to agonist-, Ca2+-, or Zn2+-induced increase in desensitization. Instead, several
      lines of evidence indicated that the developmental decrease in desensitization
      was tightly correlated with synaptic localization of the receptor, suggesting
      that association of NMDARs with proteins selectively expressed at synapses in
      mature neurons might account for developmental alterations in desensitization.
      Accordingly, we tested the role of interactions between PSD-95 (postsynaptic
      density-95) and NMDARs in regulating receptor desensitization. Overexpression of
      PSD-95 reduced NMDAR desensitization in immature neurons, whereas agents that
      interfere with synaptic targeting of PSD-95, or induce movement of NMDARs away
      from synapses and uncouple the receptor from PSD-95, increased NMDAR
      desensitization in mature neurons. We conclude that synaptic localization and
      association with PSD-95 increases stability of hippocampal neuronal NMDAR
      responses to sustained agonist exposure. Our results elucidate an additional
      mechanism for differentially regulating NMDAR function in neurons of different
      developmental stages or the response of subpopulations of NMDARs in a single
      neuron.

PMID- 14657185
TI  - Early skill learning is expressed through selection and tuning of cortically
      represented muscle synergies.
AB  - Skill learning may be based on integrating and adapting movement building blocks
      organized in the CNS. We examined at what level integration and adaptation occur
      during early skill learning, the level of individual muscles, muscle synergies or
      combinations of synergies through time, and whether these operations are
      expressed through the primary motor cortex (M1). Forelimb muscle and M1 cell
      activity were recorded over the first day of training on a reach-to-grasp task in
      rodents. Independent components analysis was used to assess how well muscle
      activation patterns could be described as time-varying combinations of synergies.
      In 3 of 11 animals, prereach M1 activity predicted the activation of different
      combinations of independent components (ICs) to perform the task. With training,
      animals increasingly adopted postures and prereach patterns of M1 activity that
      supported activation of the more successful combination. With training, animals
      also adjusted the activation magnitude (6 of 11 animals) and weights (11 of 11)
      of specific ICs that constituted the selected combination. Weights represent how
      IC activation patterns were distributed to forelimb muscles; this distribution
      pattern was adapted with training. M1 cells (37 of 100) had task-related firing
      rates that were significantly correlated with IC activation patterns. Changes in
      M1 firing rates were associated with corresponding changes in either the
      activation magnitude or weights of the correlated IC. Our data suggest that early
      skill learning is expressed through selection and tuning of M1 firing rates,
      which specify time-varying patterns of synergistic muscle contractions in the
      limb.

PMID- 14657186
TI  - Distribution of postsynaptic density (PSD)-95 and Ca2+/calmodulin-dependent
      protein kinase II at the PSD.
AB  - Postsynaptic densities (PSDs) contain proteins that regulate synaptic
      transmission. We determined the positions of calcium/calmodulin-dependent protein
      kinase II (CaMKII) and PSD-95 within the three-dimensional structure of isolated
      PSDs using immunogold labeling, rotary shadowing, and electron microscopic
      tomography. The results show that all PSDs contain a central mesh immediately
      underlying the postsynaptic membrane. Label for PSD-95 is found on both the
      cytoplasmic and cleft sides of this mesh, averaging 12 nm from the cleft side.
      All PSDs label for PSD-95. The properties of CaMKII labeling are quite different.
      Label is virtually absent on the cleft sides of PSDs, but can be heavy on the
      cytoplasmic side at a mean distance of 25 nm from the cleft. In tomograms, CaMKII
      holoenzymes can be visualized directly, appearing as labeled, tower-like
      structures reflecting the 20 nm diameter of the holoenzyme. These towers protrude
      from the cytoplasmic side of the central mesh. There appears to be a local
      organization of CaMKII, as judged by fact that the nearest-neighbor distances are
      nearly invariant over a wide range of labeling density for CaMKII. The average
      density of CaMKII holoenzymes is highly variable, ranging from zero to values
      approaching a tightly packed state. This variability is significantly higher than
      that for PSD-95 and is consistent with an information storage role for CaMKII.

PMID- 14657187
TI  - Phase-plane analysis of gaze stabilization to high acceleration head thrusts: a
      continuum across normal subjects and patients with loss of vestibular function.
AB  - We investigated the vestibulo-ocular reflex (VOR) during high-acceleration, yaw
      axis, head rotations in 12 normals and 15 patients with vestibular loss [7
      unilateral vestibular deficient (UVD) and 8 bilateral vestibular deficient
      (BVD)]. We analyzed gaze stabilization within a 200-ms window after head rotation
      began, using phase planes, which allowed simultaneous analysis of gaze velocity
      and gaze position. These "gaze planes" revealed critical dynamic information not
      easily gleaned from traditional gain measurements. We found linear relationships
      between peak gaze-velocity and peak gaze-position error when normalized to peak
      head speed and position, respectively. Values fell on a continuum, increasing
      from normals, to normals tested with very high acceleration (VHA = 10,000-20,000
      degrees/s2), to UVD patients during rotations toward the intact side, to UVD
      patients during rotations toward the lesioned side, to BVD patients. We
      classified compensatory gaze corrections as gaze-position corrections (GPCs) or
      gaze-velocity error corrections (GVCs). We defined patients as better-compensated
      when the value of their end gaze position was low relative to peak gaze position.
      In the gaze plane this criterion corresponded to relatively stereotyped patterns
      over many rotations, and appearance of high velocity (100-400 degrees/s) GPCs in
      the gaze plane ending quadrant (150-200 ms after head movement onset). In less
      compensated patients, and normals at VHA, more GVCs were generated, and GPCs were
      generated only after gaze-velocity error was minimized. These findings suggest
      that challenges to compensatory vestibular function can be from vestibular
      deficiency or novel stimuli not previously experienced. Similar patterns of
      challenge and compensation were observed in both patients with vestibular loss
      and normal subjects.

PMID- 14657188
TI  - Cloning and expression of a small-conductance Ca(2+)-activated K+ channel from
      the mouse cochlea: coexpression with alpha9/alpha10 acetylcholine receptors.
AB  - Functional interactions between ligand-gated, voltage-, and Ca(2+)-activated ion
      channels are essential to the properties of excitable cells and thus to the
      working of the nervous system. The outer hair cells in the mammalian cochlea
      receive efferent inputs from the brain stem through cholinergic nerve fibers that
      form synapses at their base. The acetylcholine released from these efferent
      fibers activates fast inhibitory postsynaptic currents mediated, to some extent,
      by small-conductance Ca(2+)-activated K+ channels (SK) that had not been cloned.
      Here we report the cloning, characterization, and expression of a complete SK2
      cDNA from the mouse cochlea. The cDNAs of the mouse cochlea alpha9 and alpha10
      acetylcholine receptors were also obtained, sequenced, and coexpressed with the
      SK2 channels. Human cultured cell lines transfected with SK2 yielded Ca(2+)
      sensitive K+ current that was blocked by dequalinium chloride and apamin, known
      blockers of SK channels. Xenopus oocytes injected with SK2 in vitro transcribed
      RNA, under conditions where only outward K+ currents could be recorded, expressed
      an outward current that was sensitive to EGTA, dequalinium chloride, and apamin.
      In HEK-293 cells cotransfected with cochlear SK2 plus alpha9/alpha10 receptors,
      acetylcholine induced an inward current followed by a robust outward current. The
      results indicate that SK2 and the alpha9/alpha10 acetylcholine receptors are
      sufficient to partly recapitulate the native hair cell efferent synaptic
      response.

PMID- 14657189
TI  - Dopamine reduces odor- and elevated-K(+)-induced calcium responses in mouse
      olfactory receptor neurons in situ.
AB  - Although D2 dopamine receptors have been localized to olfactory receptor neurons
      (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in
      ORNs, dopaminergic modulation of either odor responses or excitability in
      mammalian ORNs has not previously been demonstrated. We found that <50 microM
      dopamine reversibly suppresses odor-induced Ca2+ transients in ORNs. Confocal
      laser imaging of 300-microm-thick slices of neonatal mouse olfactory epithelium
      loaded with the Ca(2+)-indicator dye fluo-4 AM revealed that dopaminergic
      suppression of odor responses could be blocked by the D2 dopamine receptor
      antagonist sulpiride (<500 microM). The dopamine-induced suppression of odor
      responses was completely reversed by 100 microM nifedipine, suggesting that D2
      receptor activation leads to an inhibition of L-type Ca2+ channels in ORNs. In
      addition, dopamine reversibly reduced ORN excitability as evidenced by reduced
      amplitude and frequency of Ca2+ transients in response to elevated K(+), which
      activates voltage-gated Ca2+ channels in ORNs. As with the suppression of odor
      responses, the effects of dopamine on ORN excitability were blocked by the D2
      dopamine receptor antagonist sulpiride (<500 microM). The observation of
      dopaminergic modulation of odor-induced Ca2+ transients in ORNs adds to the
      growing body of work showing that olfactory receptor neurons can be modulated at
      the periphery. Dopamine concentrations in nasal mucus increase in response to
      noxious stimuli, and thus D2 receptor-mediated suppression of voltage-gated Ca2+
      channels may be a novel neuroprotective mechanism for ORNs.

PMID- 14657190
TI  - Modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by protein
      kinase A and protein kinase C.
AB  - Voltage-gated Na+ channels (VGSC) are transmembrane proteins that are essential
      for the initiation and propagation of action potentials in neuronal excitability.
      Because neurons express a mixture of Na+ channel isoforms and protein kinase C
      (PKC) isozymes, the nature of which channel is being regulated by which PKC
      isozyme is not known. We showed that DRG VGSC Nav1.7 (TTX-sensitive) and Nav1.8
      (TTX-resistant), expressed in Xenopus oocytes were differentially regulated by
      protein kinase A (PKA) and PKC isozymes using the two-electrode voltage-clamp
      method. PKA activation resulted in a dose-dependent potentiation of Nav1.8
      currents and an attenuation of Nav1.7 currents. PKA-induced increases (Nav1.8)
      and decreases (Nav1.7) in peak currents were not associated with shifts in
      voltage-dependent activation or inactivation. The PKA-mediated increase in Nav1.8
      current amplitude was prevented by chloroquine, suggesting that cell trafficking
      may contribute to the changes in Nav1.8 current amplitudes. A dose-dependent
      decrease in Nav1.7 and Nav1.8 currents was observed with the PKC activators
      phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate. PMA induced
      shifts in the steady-state activation of Nav1.7 and Nav1.8 channels by 6.5 and 14
      mV, respectively, in the depolarizing direction. The role of individual PKC
      isozymes in the regulation of Nav1.7 and Nav1.8 was determined using PKC-isozyme
      specific peptide activators and inhibitors. The decrease in the Nav1.8 peak
      current induced by PMA was prevented by a specific epsilonPKC isozyme peptide
      antagonist, whereas the PMA effect on Nav1.7 was prevented by epsilonPKC and
      betaIIPKC peptide inhibitors. The data showed that Nav1.7 and Nav1.8 were
      differentially modulated by PKA and PKC. This is the first report demonstrating a
      functional role for epsilonPKC and betaIIPKC in the regulation of Nav1.7 and
      Nav1.8 Na+ channels. Identification of the particular PKC isozymes(s) that
      mediate the regulation of Na+ channels is essential for understanding the
      molecular mechanism involved in neuronal ion channel regulation in normal and
      pathological conditions.

PMID- 14657191
TI  - Effect of rhythmic arm movement on reflexes in the legs: modulation of soleus H
      reflexes and somatosensory conditioning.
AB  - During locomotor tasks such as walking, running, and swimming, the arms move
      rhythmically with the legs. It has been suggested that connections between the
      cervical and lumbosacral spinal cord may mediate some of this interlimb
      coordination. However, it is unclear how these interlimb pathways modulate reflex
      excitability during movement. We hypothesized that rhythmic arm movement would
      alter the gain of reflex pathways in the stationary leg. Soleus H-reflexes
      recorded during arm cycling were compared with those recorded at similar
      positions with the arms stationary. Nerve stimulation was delivered with the
      right arm at approximately 70 degrees shoulder flexion or 10 degrees shoulder
      extension. H-reflexes were evoked alone (unconditioned) or with sural or common
      peroneal nerve (CP) conditioning to decrease or increase soleus IA presynaptic
      inhibition, respectively. Both conditioning stimuli were also delivered with no H
      reflex stimulation. H-reflex amplitudes were compared at similar M-wave
      amplitudes and activation levels of the soleus. Arm cycling significantly reduced
      (P < 0.05) unconditioned soleus H-reflexes at shoulder flexion by 21.7% and at
      shoulder extension by 8.8% compared with static controls. The results demonstrate
      a task-dependent modulation of soleus H-reflexes between arm cycling and
      stationary trials. Sural nerve stimulation facilitated H-reflexes at shoulder
      extension but not at shoulder flexion during static and cycling trials. CP nerve
      stimulation significantly reduced H-reflex amplitude in all conditions. Reflexes
      in soleus when sural and CP nerve stimulation were delivered alone, were not
      different between cycling and static trials; thus the task-dependent change in H
      reflex amplitude was not due to changes in motoneuron excitability. Therefore
      modulation occurred at a pre-motoneuronal level, probably by presynaptic
      inhibition of the IA afferent volley. Results indicate that neural networks
      coupling the cervical and lumbosacral spinal cord in humans are activated during
      rhythmic arm movement. It is proposed that activation of these networks may
      assist in reflex linkages between the arms and legs during locomotor tasks.

PMID- 14657192
TI  - Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid
      receptors.
AB  - Nicotine is an alkaloid that is used by large numbers of people. When taken into
      the body, it produces a myriad of physiological actions that occur primarily
      through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We
      have explored its ability to modulate TRPV1 receptors and voltage-gated sodium
      channels. The reason for investigating nicotine's effect on sodium channels is to
      obtain a better understanding of its anti-nociceptive properties. The reasons for
      investigating its effects on capsaicin-activated TRPV1 channels are to understand
      how it may modulate this channel that is involved in pain, inflammation, and
      gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal
      ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties
      by decreasing the number of evoked action potentials and by inhibiting
      tetrodotoxin-resistant sodium currents. This anesthetic property can be produced
      without the necessity of activating nAChRs. Nicotine also modulates TRPV1
      receptors inducing a several-fold increase in capsaicin-activated currents in
      both TG neurons and in cells with heterologously expressed TRPV1 receptors. This
      sensitizing effect does not require the activation of nAChRs. Nicotine did not
      alter the threshold temperature (approximately 41 degrees C) of heat-activated
      currents in TG neurons that were attributed to arise from the activation of TRPV1
      receptors. In this regard, its effect on TRPV1 receptors differs from those of
      ethanol that has been shown to increase the capsaicin-activated current but
      decrease the threshold temperature. These studies document several new effects of
      nicotine on channels involved in nociception and indicate how they may impact
      physiological processes involving pain and gustation.

PMID- 14657193
TI  - Does head rotation contribute to gaze stability during passive translations?
AB  - Active translations of human subjects are nearly perfectly compensated by a
      combined rotation of both the eyes and the head. Because vestibuloocular reflex
      (VOR) gain is less than perfect during passive translations with near targets in
      head-fixed subjects, there is a possibility that the compensatory head rotation
      observed during natural behavior represents a vestibularly driven head reflex
      [translational vestibulocollic reflex (TVCR)]. The TVCR could elicit a horizontal
      rotation of the head during lateral linear acceleration that contributes to gaze
      stabilization. To investigate this hypothesis, we examined whether a horizontal
      rotation of the head contributes to gaze stability during passive lateral
      translation in rhesus monkeys whose head was free to rotate in the horizontal
      plane. Motion frequency was varied between 0.5 and 5 Hz while animals fixated
      targets at distances of 12-102 cm. We did not find evidence supporting the
      existence of a TVCR. Specifically, during motion at frequencies between 0.5 and 2
      Hz, horizontal head rotation was negligible. During 4- and 5-Hz oscillations,
      there was a clear and consistent horizontal rotation of the head, but responses
      were always anticompensatory to gaze stabilization; that is, the head rotated in
      the same direction as head translation and oppositely to the direction of gaze
      rotation. Furthermore, there was no difference in gaze stability between the head
      free and head-fixed conditions. Thus we conclude that the compensatory head
      rotation observed in human studies of active gaze movements could represent a
      strategy and/or a motor command contribution to gaze stabilization, rather than a
      simple vestibularly driven reflex.

PMID- 14657194
TI  - Chemical synthesis of (22E)-3 alpha,6 beta,7 beta-trihydroxy-5 beta-chol-22-en-24
      oic acid and its taurine and glycine conjugates: a major bile acid in the rat.
AB  - A method for the synthesis of Delta(22)-beta-muricholic acid (Delta(22)-beta
      MCA), (22E)-3 alpha,6 beta,7 beta-trihydroxy-5 beta-chol-22-en-24-oic acid, and
      its taurine and glycine conjugates (Delta(22)-beta-muricholyltaurine and
      Delta(22)-beta-muricholylglycine) is described. The key intermediate, 3 alpha,6
      beta,7 beta-triformyloxy-23,24-dinor-5 beta-cholan-22-al, was prepared from beta
      muricholic acid (beta-MCA) via the 24-nor-22-ene and 24-nor-22,23-diol
      derivatives. Wittig reaction of the aldehyde with (carbomethoxymethylene)
      triphenylphosphorane and subsequent hydrolysis gave (unconjugated) Delta(22)-beta
      MCA. Condensation reaction of the unconjugated acid with taurine or glycine
      methyl ester using diethylphosphorocyanide yielded the naturally occurring
      taurine or glycine conjugate (N-acylamidate) of Delta(22)-beta-MCA. These
      synthetic reference compounds are now available for investigation of the
      metabolism of beta-MCA by bacterial and hepatic enzymes in the rat and should
      also be useful as substrates for reductive deuteration or tritiation to give the
      22,23-(2)H or (3)H-beta-MCA.

PMID- 14657195
TI  - Apolipoprotein composition of HDL in cholesteryl ester transfer protein
      deficiency.
AB  - Our purpose was to compare HDL subpopulations, as determined by nondenaturing two
      dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I
      (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound
      heterozygous, and homozygous subjects for cholesteryl ester transfer protein
      (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and
      homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL
      cholesterol values that were 64, 168, and 203% higher than those in controls,
      respectively. Heterozygotes had approximately 50% lower pre-beta-1 and more than
      2-fold higher levels of alpha-1 and pre-alpha-1 particles than controls. Three of
      the five heterozygotes' alpha-1 particles also contained apoA-II, which was not
      seen in controls. Compound heterozygotes and homozygotes had very large particles
      not observed in controls and heterozygotes. These particles contained apoA-I,
      apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre-beta
      1 levels. Our data indicate that CETP deficiency results in the formation of very
      large HDL particles containing all of the major HDL apolipoproteins except for
      apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP
      deficient patients, especially those with high levels of alpha-1 containing apoA
      I but no apoA-II, represent an improved anti-atherogenic state, although this
      might not be the case for compound heterozygotes and homozygotes with very large,
      undifferentiated HDL particles.

PMID- 14657196
TI  - Ethnic differences in hepatic lipase and HDL in Japanese, black, and white
      Americans: role of central obesity and LIPC polymorphisms.
AB  - Hepatic lipase activity (HLA) is a determinant of HDL levels, and a polymorphism
      in the hepatic lipase gene (LIPC) promoter (C-514T) has been hypothesized to
      account for higher HDL in blacks and Japanese compared with whites. To determine
      whether the polymorphism contributes to ethnic differences in HDL, we compared
      LIPC allele frequencies and HLA in Japanese American (JA; n = 84), black American
      (BA; n = 94), and white American (WA; n = 110) men and women. The LIPC
      polymorphism was associated with HLA in all cohorts (BA, P = 0.012; JA, P =
      0.008; WA, P = 0.009). WA men had 49% and 58% higher HLA than BA and JA men,
      respectively (both P < 0.05), yet no differences in HLA were found between the
      women. The higher HLA in the WA men remained after adjustment for the LIPC
      polymorphism's effect on HLA (P = 0.037) but was erased after adjustment for
      waist-to-hip-ratio (P = 0.46). Although the WA men had lower HDL and HDL(3) than
      the JA and BA men (all P < 0.05), there were no differences in HDL(2), implying
      that variance in HLA may not underlie the ethnic differences in HDL levels. These
      results suggest that 1) the LIPC promoter polymorphism contributes to variation
      in HLA and HDL(2) in the three ethnic groups; 2) WA men had higher HLA than BA
      and JA men, related to ethnic differences in central adiposity but not LIPC
      allele frequency; and 3) the higher HLA in WA men did not contribute to the
      ethnic differences in HDL, as the differences in HDL were made up entirely of
      differences in HDL(3) and not HDL(2).

PMID- 14657197
TI  - Isolation, partial purification, and characterization of a novel petromyzonol
      sulfotransferase from Petromyzon marinus (lamprey) larval liver.
AB  - We have isolated, partially purified, and characterized the 5 alpha-petromyzonol
      (5 alpha-PZ), (5 alpha-cholan- 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-)
      sulfotransferase (PZ-SULT) from larval lamprey liver. Crude liver extracts
      exhibited a PZ-SULT activity of 0.9120 pmol/min/mg in juvenile and 12.62
      pmol/min/mg in larvae. Using crude larval liver extracts and various 5 beta
      cholan substrates and allocholic acid there was negligible activity, however,
      with 5 alpha-PZ and 3-keto-5 alpha-PZ the SULT activity was 231.5 pmol/min/mg and
      180.8 pmol/min/mg respectively. This established that the sulfotransferase of
      lamprey larval liver extracts prefers (5 alpha) substrates and it is selective
      for hydroxyl at C-24. PZ-SULT was purified through various chromatography
      procedures. Partially purified PZ-SULT exhibited a pH optimum of 8.0, a
      temperature optimum of 22 degrees C, and activity was linear for 1h. PZ-SULT
      exhibited a K(m) of 2.5 microM for PAPS and a K(m) of 8 microM for PZ. The
      affinity purified peak PZ-SULT exhibited a specific activity of 2,038
      pmol/min/mg. The peak protein upon SDS-PAGE, correlated to an Mw 47 kDa.
      Photoaffinity labeling with PAP(35)S, specifically crosslinked the 47 kDa
      protein, further confirming the identity of PZ-SULT. Partial amino acid
      sequencing of the putative 47 kDa PZ-SULT protein yielded a peptide sequence
      (M)SISQAVDAAFXEI, which possessed an overall (approximately 35-40%) homology with
      mammalian SULT2B1a.

PMID- 14657198
TI  - The structural requirements for ceramide activation of serine-threonine protein
      phosphatases.
AB  - The protein phosphatases1 (PP1) and 2A (PP2A) serve as ceramide-activated protein
      phosphatases (CAPP). In this study, the structural requirements for interaction
      between ceramide and CAPP were determined. D-erythro-C(6) ceramide activated the
      catalytic subunit of PP2A (PP2Ac) approximately 3-fold in a stereospecific
      manner. In contrast, saturation of the 4-5 double bond, producing D-erythro
      dihydro C(6) ceramide, inhibited PP2Ac (IC(50) = 8.5 microM). Furthermore, phyto
      C(6) ceramide, D-erythro-dehydro C(6) ceramide, and D-erythro-cis-C(6) ceramide
      had no effect on PP2Ac activity. Modification of the sphingoid chain also
      abolished the ability of ceramide to activate PP2Ac. Further studies demonstrated
      the requirement for the amide group, the primary hydroxyl group, and the
      secondary hydroxyl group of the sphingoid backbone for activation of PP2Ac
      through the synthesis and evaluation of D-erythro-urea C(6) ceramide, L-erythro
      urea C(6) ceramide, D-erythro-N-methyl C(6) ceramide, D-erythro-L-O-methyl C(6)
      ceramide, D-erythro-3-O-methyl C(6) ceramide, and (2S) 3-keto C(6) ceramide. None
      of these compounds induced significant activation of PP2Ac. Liposome binding
      studies were also conducted using analogs of D-erythro-C C(6) ceramide, and the
      results showed that the ability of ceramide analogs to influence CAPP (activation
      or inhibition) was associated with the ability of the analogs to bind to CAPP.
      This study demonstrates strict structural requirements for interaction of
      ceramide with CAPP, and disclose ceramide as a very specific regulator of CAPP.
      The studies also begin to define features that transform ceramide analogs into
      inhibitors of CAPP.

PMID- 14657199
TI  - Insulin resistance is associated with increased cholesterol synthesis and
      decreased cholesterol absorption in normoglycemic men.
AB  - Type 2 diabetes has been associated with high synthesis and low absorption of
      cholesterol independent of weight, indicating that insulin resistance may be a
      link between glucose and cholesterol metabolism. Therefore, we investigated the
      relationship of serum cholesterol precursors, reflecting cholesterol synthesis,
      and serum plant sterols and cholestanol, reflecting cholesterol absorption
      efficiency, with insulin sensitivity measured with the hyperinsulinemic
      euglycemic clamp in 72 healthy normoglycemic men. Men in the most insulin
      resistant tertile had higher serum cholesterol precursor ratios (P < 0.05),
      whereas no significant differences in serum absorption sterols were observed. In
      bivariate analysis, cholesterol synthesis markers correlated with fasting insulin
      (r = 0.36-0.46, P < 0.01) and the rates of insulin-stimulated whole-body glucose
      uptake (WBGU; r = -0.37-0.40, P < 0.01). Also, cholesterol absorption markers
      correlated with fasting insulin and WBGU (P < 0.05). Fasting insulin correlated
      with desmosterol (r = 0.286, P = 0.015) and lathosterol (r = 0.248, P = 0.037)
      even when the rates of WBGU and body mass index (BMI) were controlled for. We
      conclude that insulin resistance is linked to high cholesterol synthesis and
      decreased cholesterol absorption. Because fasting insulin correlated with
      cholesterol synthesis independent of the rates of BMI and WBGU, it is possible
      that regulation of cholesterol synthesis by hyperinsulinemia may be a link
      between insulin resistance and cholesterol metabolism.

PMID- 14657200
TI  - Dimerization of the scavenger receptor class B type I: formation, function, and
      localization in diverse cells and tissues.
AB  - This study has examined the dimeric/oligomeric forms of scavenger receptor class
      B type I (SR-BI) and its alternatively spliced form, SR-BII, in a diverse group
      of cells and tissues: i.e., normal and hormonally altered tissues of mice and
      rats as well as tissues of transgenic animals and genetically altered
      steroidogenic and nonsteroidogenic cells overexpressing the SR-B proteins. Using
      both biochemical and morphological techniques, we have seen that these dimeric
      and higher order oligomeric forms of SR-BI expression are strongly associated
      with both functional and morphological expression of the selective HDL
      cholesteryl ester uptake pathway. Rats and mice show some species differences in
      expression of SR-BII dimeric forms; this difference does not extend to the use of
      SR-B cDNA types for transfection purposes. In a separate study, cotransfection of
      HEK293 cells with cMyc and V5 epitope-tagged SR-BI permitted coprecipitation and
      quantitative coimmunocytochemical measurements at the electron microscope level,
      suggesting that much of the newly expressed SR-BI protein in stimulated cells
      dimerizes and that the SR-BI dimers are localized to the cell surface and
      specifically to microvillar or double membraned intracellular channels. These
      combined data suggest that SR-BI self-association represents an integral step in
      the selective cholesteryl ester uptake process.

PMID- 14657201
TI  - Selective changes of docosahexaenoic acid-containing phospholipid molecular
      species in monkey testis during puberty.
AB  - Puberty has a profound effect upon the biochemical composition of the testis. We
      previously demonstrated that puberty was accompanied by great increases in the
      content of docosahexaenoic acid (DHA; 22:6 n-3) and dihomogamma-linoleic acid
      (20:3 n-6) and decreases in arachidonic acid (AA; 20:4 n-6) in the phospholipids
      of testis. In this report, we analyze the composition of the phospholipid
      molecular species of the ethanolamine and choline glycerophospholipids in the
      testis of prepubertal (2 years old) and young adult (7-8 years old) monkeys,
      There was an increase in the DHA species and a decrease in arachidonic species.
      Interestingly, with few exceptions, among the three molecules with DHA or AA at
      the sn-2 position, only 16:0-22:6 and 18:0-20:4 changed selectively in opposite
      directions for both ethanolamine and choline glycerophospholipids. In contrast,
      there was no such selectivity seen in molecular species containing dihomogamma
      linoleic acid or linoleic acid at the sn-2 position. All three dihomogamma
      linoleic acid species increased and all three linoleic acid species decreased
      during puberty. In summary, at puberty, i.e., the onset of spermatogenesis, there
      are selective changes in the phospholipid molecular species, particularly those
      containing DHA and AA. These changes suggest a specific functional role of DHA
      containing molecular species in the lipid bilayer membranes of sperm cells. A
      possible link between the composition of DHA-phospholipid molecular species and
      cellular function is discussed.

PMID- 14657203
TI  - Haptoglobin release by human adipose tissue in primary culture.
AB  - Haptoglobin is a putative adiposity marker because its concentration in blood is
      increased in obese humans. The present studies examined haptoglobin release by
      explants of adipose tissue in primary culture. Haptoglobin was released by
      explants of human visceral and subcutaneous adipose tissue at a nearly linear
      rate over 48 h. Explants of visceral adipose tissue released more haptoglobin
      than did explants of subcutaneous adipose tissue. The release of haptoglobin was
      quite variable, but there was a close correlation between haptoglobin release by
      visceral adipose tissue and that by explants of subcutaneous tissue from the same
      individual. Dexamethasone and niflumic acid, a cyclooxygenase-2 inhibitor, both
      inhibited haptoglobin release. There was release of haptoglobin by both isolated
      adipocytes and the adipose tissue matrix remaining after collagenase digestion of
      human adipose tissue. However, the amount of haptoglobin released by human
      adipose tissue explants in primary culture was quite low in relationship to the
      circulating level of haptoglobin.

PMID- 14657202
TI  - Selective sterol accumulation in ABCG5/ABCG8-deficient mice.
AB  - The ATP binding cassette (ABC) transporters ABCG5 and ABCG8 limit intestinal
      absorption and promote biliary secretion of neutral sterols. Mutations in either
      gene cause sitosterolemia, a rare recessive disease in which plasma and tissue
      levels of several neutral sterols are increased to varying degrees. To determine
      why patients with sitosterolemia preferentially accumulate noncholesterol
      sterols, levels of cholesterol and the major plant sterols were compared in
      plasma, liver, bile, and brain of wild-type and ABCG5/ABCG8-deficient (G5G8(-/-))
      mice. The total sterol content of liver and plasma was similar in G5G8(-/-) mice
      and wild-type animals despite an approximately 30-fold increase in noncholesterol
      sterol levels in the knockout animals. The relative enrichment of each sterol in
      the plasma and liver of G5G8(-/-) mice (stigmasterol > sitosterol = cholestanol >
      bassicasterol > campesterol > cholesterol) reflected its relative enrichment in
      the bile of wild-type mice. These results indicate that 24-alkylated, Delta22,
      and 5alpha-reduced sterols are preferentially secreted into bile and that
      preferential biliary secretion of noncholesterol sterols by ABCG5 and ABCG8
      prevents the accumulation of these sterols in normal animals. The mRNA levels for
      13 enzymes in the cholesterol biosynthetic pathway were reduced in the livers of
      the G5G8(-/-) mice, despite a 50% reduction in hepatic cholesterol level. Thus,
      the accumulation of sterols other than cholesterol is sensed by the cholesterol
      regulatory machinery.

PMID- 14657204
TI  - Discovery of new G protein-coupled receptors for lipid mediators.
AB  - Successful sequencing of the human genome has opened a new era in the life
      sciences and has greatly accelerated biomedical research. Among various research
      endeavors benefiting from established genomic information, one of the most
      fruitful areas is the research on orphan G protein-coupled receptors (GPCRs).
      Many intercellular mediators, including peptides, lipids, and other small
      molecules, have found their GPCRs in the plasma membrane, e.g., relaxin and
      tyramine. In the past 14 months, more than one dozen papers have been published
      reporting the finding of intercellular lipid mediators acting on rhodopsin family
      GPCRs. This review focuses primarily on intercellular lipid mediators and their
      recently discovered GPCRs.

PMID- 14657205
TI  - Phospholipase A2 in the central nervous system: implications for
      neurodegenerative diseases.
AB  - Phospholipase A2 (PLA2) belongs to a family of enzymes that catalyze the cleavage
      of fatty acids from the sn-2 position of phospholipids. There are more than 19
      different isoforms of PLA2 in the mammalian system, but recent studies have
      focused on three major groups, namely, the group IV cytosolic PLA2, the group II
      secretory PLA2 (sPLA2), and the group VI Ca(2+)-independent PLA2. These PLA2s are
      involved in a complex network of signaling pathways that link receptor agonists,
      oxidative agents, and proinflammatory cytokines to the release of arachidonic
      acid (AA) and the synthesis of eicosanoids. PLA2s acting on membrane
      phospholipids have been implicated in intracellular membrane trafficking,
      differentiation, proliferation, and apoptotic processes. All major groups of PLA2
      are present in the central nervous system (CNS). Therefore, this review is
      focused on PLA2 and AA release in neural cells, especially in astrocytes and
      neurons. In addition, because many neurodegenerative diseases are associated with
      increased oxidative and inflammatory responses, an attempt was made to include
      studies on PLA2 in cerebral ischemia, Alzheimer's disease, and neuronal injury
      due to excitotoxic agents. Information from these studies has provided clear
      evidence for the important role of PLA2 in regulating physiological and
      pathological functions in the CNS.

PMID- 14657206
TI  - Functions of lipoprotein receptors in neurons.
AB  - The LDL receptor (LDLR) family is comprised of several multifunctional cell
      surface proteins that bind and endocytose ligands with diverse biological
      functions. One ligand common to all LDLR family members is apolipoprotein E
      (apoE), a lipid transport protein that also plays a central role in the
      pathogenesis of neurodegeneration in Alzheimer's disease. This review discusses
      the role of apoE and its receptors in the central nervous system and, in
      particular, the signaling mechanisms by which two members of the LDLR gene
      family, apoE receptor-2 and VLDL receptor, control brain development, normal
      neuronal positioning, and neurotransmission in the adult brain.

PMID- 14657207
TI  - The roles of insulin and hyperglycemia in sepsis pathogenesis.
AB  - Hyperglycemia is a risk marker of morbidity and mortality in acute critical
      illness, and insulin therapy seems to be beneficial in this patient group.
      Whether this is true for a population of sepsis patients, as such, has not been
      investigated in clinical trials, but evidence from in vitro studies and
      experimental sepsis suggests that this may be the case. The endocrinology of
      septic patients is characterized by a shift in the balance between insulin and
      its counter-regulatory hormones favoring the latter. This leads to prominent
      metabolic derangements composed of high release and low use of glucose, amino
      acids, and free fatty acids (FFA), resulting in increased blood levels of these
      substrates. Circulating, proinflammatory mediators further enhance this state of
      global catabolism. Increased levels of glucose and FFA have distinct effects on
      inflammatory signaling leading to additional release of proinflammatory mediators
      and endothelial and neutrophil dysfunction. Insulin has the inherent capability
      to counteract the metabolic changes observed in septic patients. Concomitantly,
      insulin therapy may act as a modulator of inflammatory pathways inhibiting the
      unspecific, inflammatory activation caused by metabolic substrates. Given these
      properties, insulin could conceivably be serving a dual purpose for the benefit
      of septic patients.

PMID- 14657208
TI  - Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion
      injury: involvement of cytokine/chemokines and PMN.
AB  - In this study, we have assessed the activation of the cannabinoid CB2 receptor
      (CB2-R) in a model of mouse myocardial ischemia/reperfusion (I/R). The results
      show that treatment of animals with WIN55212-2, a CB1/CB2-R agonist, given 30 min
      before induction of I/R, significantly reduced the extent of infarct size (IS) in
      the area at risk, as measured 2.5 h later, with almost a 51% inhibition observed
      at the dose tested of 3.5 mg/kg intraperitoneally (i.p.). The protective effect
      of WIN55212-2 was almost abolished by the selective CB2-R antagonist AM630 (1
      mg/kg i.p.) and not affected by the selective CB1-R antagonist AM251 (3 mg/kg
      i.p.). The CB2-R antagonist administered alone produced a slight but significant
      (P<0.05) increase in IS compared with vehicle alone. The protection afforded by
      WIN55212-2 was paralleled by lower values of myeloperoxidase activity and
      interleukin-1beta and of the CXC chemokine ligand 8 into the injured tissue. In
      conclusion, we demonstrate for the first time that exogenous and endogenous CB2-R
      activation reduces the leukocyte-dependent myocardial damage associated with an
      I/R procedure.

PMID- 14657209
TI  - Age-associated alterations in the recruitment of signal-transduction proteins to
      lipid rafts in human T lymphocytes.
AB  - Aging is associated with a decline in T cell activation and proliferation, but
      the underlying mechanisms are not fully understood. Recent findings suggest that
      lipid rafts act as a platform in the initiation of T cell activation by
      selectively recruiting signaling proteins associated with formation of the
      initial complex of signal transduction. We tested the hypothesis that lipid raft
      properties are altered in T lymphocytes from elderly, healthy individuals in
      comparison with young subjects. Results showed that the cholesterol content of
      lipid rafts derived from these cells was consistently higher in the case of
      elderly donors and that membrane fluidity was decreased. In addition, lipid rafts
      coalescence to the site of T cell receptor engagement was impaired in T cells
      from elderly donors. The recruitment of p56(lck), linker of activated T cells,
      and their tyrosine-phosphorylated forms to lipid rafts was decreased in activated
      T cells from aged individuals. CD45 was not recruited to the lipid raft fractions
      in either group of subjects. Our data suggest that some properties of lipid rafts
      are altered in aging, and this finding may be part of the causes for the decline
      in T cell functions that are observed in elderly individuals.

PMID- 14657210
TI  - The significance of carbohydrates on G-CSF: differential sensitivity of G-CSFs to
      human neutrophil elastase degradation.
AB  - It has been reported recently that granulocyte-colony stimulating factor (G-CSF)
      is degraded upon exposure to human neutrophil elastase (HNE), and this has a
      negative effect on the ability of the cytokine to promote the in vitro
      proliferation and maturation of CD34+ cells. This has important implications on
      the possible in vivo role of elastase in providing negative feedback to
      granulopoiesis by the direct antagonism of G-CSF. The cytokine used in that study
      was expressed in Escherichia coli [and was nonglycosylated (NG)], unlike the
      naturally occurring cytokine, which is an O-linked glycoprotein. As a Chinese
      hamster ovary-derived (glycosylated) cytokine is available, we compared the
      susceptibility of NG and glycosylated G-CSF to elastase degradation by incubating
      the cytokines with HNE and assessing its impact by sodium dodecyl sulfate gel
      electrophoresis and bioassay. We confirmed the ability of elastase to degrade NG
      G-CSF in a time- and concentration-dependent manner and found this was associated
      with a reduction in biological activity of the cytokine. Glycosylated G-CSF,
      however, was more resistant to elastase degradation, although prolonged exposure
      did lead to degradation and decreased biological activity. The significance of
      sugar residues on glycosylated G-CSF in providing protection against the effects
      of elastase was investigated using enzymatically deglycosylated G-CSF and a
      mutated form of the G-CSF molecule that was expressed in yeast but was NG. The
      possible role of HNE in serum-induced inactivation of NG G-CSF was also
      considered.

PMID- 14657211
TI  - The induction of Toll-like receptor tolerance enhances rather than suppresses HIV
      1 gene expression in transgenic mice.
AB  - Microbial-induced proinflammatory pathways are thought to play a key role in the
      activation of human immunodeficiency virus type 1 (HIV-1) gene expression. The
      induction of Toll-like receptor (TLR) tolerance leads to a complex reprogramming
      in the pattern of inflammatory gene expression and down-modulates tumor necrosis
      factor alpha (TNF-alpha), interleukin (IL)-1, and IL-6 production. Using
      transgenic (Tg) mice that incorporate the entire HIV-1 genome, including the long
      terminal repeat, we have previously demonstrated that a number of different TLR
      ligands induce HIV-1 gene expression in cultured splenocytes as well as purified
      antigen-presenting cell populations. Here, we have used this model to determine
      the effect of TLR-mediated tolerance as an approach to inhibiting microbial
      induced viral gene expression in vivo. Unexpectedly, Tg splenocytes and
      macrophages, rendered tolerant in vitro to TLR2, TLR4, and TLR9 ligands as
      assessed by proinflammatory cytokine secretion and nuclear factor-kappaB
      activation, showed enhanced HIV-1 p24 production. A similar enhancement was
      observed in splenocytes tolerized and then challenged with heterologous TLR
      ligands. Moreover, TLR2- and TLR4-homotolerized mice demonstrated significantly
      increased plasma p24 production in vivo despite lower levels of TNF-alpha.
      Together, these results demonstrate that HIV-1 expression is enhanced in TLR
      reprogrammed host cells, possibly reflecting a mechanism used by the virus to
      escape the effects of microbial-induced tolerance during natural infection in
      vivo.

PMID- 14657212
TI  - Altering immune tolerance therapeutically: the power of negative thinking.
AB  - The etiology of most human autoimmune diseases remains largely unknown. However,
      investigators have identified several negative regulatory mechanisms acting at
      the level of innate and/or adaptive immunity. Mutations resulting in a deficiency
      of some key regulatory molecules are associated with systemic or organ-specific
      inflammatory disorders, which often have a prominent autoimmune component.
      Genetic studies have implicated the negative regulator cytotoxic T-lymphocyte
      antigen 4 (CTLA-4) and other regulatory molecules in human autoimmune diseases.
      In addition to CTLA-4, key inhibitory molecules include programmed death 1 and B
      and T lymphocyte attenuator. Transforming growth factor beta1 and interleukin-10
      also play major anti-inflammatory and regulatory roles. Tumor cells and
      infectious agents use negative regulatory pathways to escape immunity. The
      therapeutic blockage of negative signaling (particularly of CTLA-4) increases
      immunity against tumor antigens but also induces or aggravates autoimmune
      diseases. It appears that under normal conditions, the immune system is under
      strong "negative influences" that prevent autoimmunity and that release of this
      suppression results in disease. Regulation involves communication between the
      immune system and nonlymphoid tissues, and the latter can deliver inhibitory or
      stimulatory signals. Recent studies reveal that the generation of negative
      signals by selective engagement of inhibitory molecules is feasible and is likely
      to be of therapeutic benefit in autoimmune diseases and allograft rejection.

PMID- 14657213
TI  - Anti-inflammatory and antiproliferative actions of PPAR-gamma agonists on T
      lymphocytes derived from MS patients.
AB  - Peroxisomal proliferator-activated receptors (PPARs) belong to a nuclear receptor
      superfamily of ligand-activated transcription factors. The PPAR-gamma isoform is
      expressed in human T lymphocytes, and oral administration of PPAR-gamma agonists
      ameliorates the clinical course and histopathological features in experimental
      autoimmune encephalomyelitis, an animal model for multiple sclerosis, suggesting
      a potential role for PPAR-gamma agonists in the treatment of autoimmune diseases.
      To assess a potential therapeutic role of PPAR-gamma agonists in multiple
      sclerosis, we compared the immunomodulatory effects of the thiazolidinedione
      (TZD) drugs pioglitazone (PIO) and ciglitazone and the non-TZD PPAR-gamma agonist
      GW347845 on human T leukemia cells (Jurkat cells) and phytohemagglutinin (PHA)
      stimulated peripheral blood mononuclear cells (PBMCs) derived from 21 multiple
      sclerosis patients and 12 healthy donors. PIO, ciglitazone, and GW347845
      suppressed PHA-induced T cell proliferation by 40-50% and secretion of interferon
      gamma and tumor necrosis factor alpha, by 30-50%. Inhibition of proliferation was
      increased to approximately 80% and that of proinflammatory cytokine secretion, to
      80-90% when PBMCs were first preincubated with PPAR-gamma agonists and re-exposed
      at the time of PHA stimulation, indicating a sensitizing effect of PPAR-gamma
      agonists. Inhibition of proliferation was also observed in the tetanus toxoid
      specific T cell line KHS.TT2, albeit to a lesser extent. The antiproliferative
      effects of PIO and GW347845 were accompanied by a decrease of cell viability.
      Electron microscopy and Western blot analysis revealed DNA condensation and down
      regulation of bcl-2, suggesting the induction of apoptosis in activated T
      lymphocytes. In summary, the data support the potential use of PPAR-gamma
      agonists as immunomodulatory, therapeutic agents for autoimmune diseases.

PMID- 14657214
TI  - Modulation of macrophage differentiation and activation by decoy receptor 3.
AB  - Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor
      receptor superfamily and is readily detected in certain cancer patients.
      Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell
      responses to a T helper cell type 2 phenotype. In this study, we further asked
      its ability to modulate CD14+ monocyte differentiation into macrophages induced
      by macrophage-colony stimulating factor in vitro. We found that DcR3.Fc was able
      to modulate the expression of several macrophage markers, including CD14, CD16,
      CD64, and human leukocyte antigen-DR. In contrast, the expression of CD11c, CD36,
      CD68, and CD206 (mannose receptor) was not affected in the in vitro culture
      system. Moreover, phagocytic activity toward immune complexes and apoptotic
      bodies as well as the production of free radicals and proinflammatory cytokines
      in response to lipopolysaccharide were impaired in DcR3.Fc-treated monocyte
      derived macrophages. This suggests that DcR3.Fc might have potent, suppressive
      effects to down-regulate the host-immune system.

PMID- 14657216
TI  - Expression of self-antigen in the thymus: a little goes a long way.

PMID- 14657217
TI  - Superior protection against malaria and melanoma metastases by a C-glycoside
      analogue of the natural killer T cell ligand alpha-Galactosylceramide.
AB  - alpha-Galactosylceramide (alpha-GalCer) is a glycolipid that stimulates natural
      killer T cells to produce both T helper (Th) 1 and Th2 cytokines. This property
      enables alpha-GalCer to ameliorate a wide variety of infectious, neoplastic, and
      autoimmune diseases; however, its effectiveness against any one disease is
      limited by the opposing activities of the induced Th1 and Th2 cytokines. Here, we
      report that a synthetic C-glycoside analogue of alpha-GalCer, alpha-C
      galactosylceramide (alpha-C-GalCer), acts as natural killer T cell ligand in
      vivo, and stimulates an enhanced Th1-type response in mice. In two disease models
      requiring Th1-type responses for control, namely malaria and melanoma metastases,
      alpha-C-GalCer exhibited a 1,000-fold more potent antimalaria activity and a 100
      fold more potent antimetastatic activity than alpha-GalCer. Moreover, alpha-C
      GalCer consistently stimulated prolonged production of the Th1 cytokines
      interferon-gamma and interleukin (IL)-12, and decreased production of the Th2
      cytokine IL-4 compared with alpha-GalCer. Finally, alpha-C-GalCer's enhanced
      therapeutic activity required the presence of IL-12, which was needed to
      stimulate natural killer cells for optimal interferon-gamma production, but did
      not affect IL-4. Overall, our results suggest that alpha-C-GalCer may one day be
      an excellent therapeutic option for diseases resolved by Th1-type responses.

PMID- 14657218
TI  - Dendritic cells initiate immune control of epstein-barr virus transformation of B
      lymphocytes in vitro.
AB  - The initiation of cell-mediated immunity to Epstein-Barr virus (EBV) has been
      analyzed with cells from EBV-seronegative blood donors in culture. The addition
      of dendritic cells (DCs) is essential to prime naive T cells that recognize EBV
      latent antigens in enzyme-linked immunospot assays for interferon gamma secretion
      and eradicate transformed B cells in regression assays. In contrast, DCs are not
      required to control the outgrowth of EBV-transformed B lymphocytes from
      seropositive donors. Enriched CD4+ and CD8+ T cells mediate regression of EBV
      transformed cells in seronegative and seropositive donors, but the kinetics of T
      dependent regression occurs with much greater speed with seropositives. EBV
      infection of DCs cannot be detected by reverse transcription-polymerase chain
      reaction with primers specific for mRNA for the EBNA1 U and K exons. Instead, DCs
      capture B cell debris and generate T cells specific for EBV latency antigens. We
      suggest that the cross-presentation of EBV-latent antigens from infected B cells
      by DCs is required for the initiation of EBV-specific immune control in vivo and
      that future EBV vaccine strategies should target viral antigens to DCs.

PMID- 14657219
TI  - An immunologically privileged retinal antigen elicits tolerance: major role for
      central selection mechanisms.
AB  - Immunologically privileged retinal antigens can serve as targets of experimental
      autoimmune uveitis (EAU), a model for human uveitis. The tolerance status of
      susceptible strains, whose target antigen is not expressed in the thymus at
      detectable levels, is unclear. Here, we address this issue directly by analyzing
      the consequences of genetic deficiency versus sufficiency of a uveitogenic
      retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). IRBP
      knockout (KO) and wild-type (WT) mice on a highly EAU-susceptible background were
      challenged with IRBP. The KO mice had greatly elevated responses to IRBP, an
      altered recognition of IRBP epitopes, and their primed T cells induced
      exacerbated disease in WT recipients. Ultrasensitive immunohistochemical staining
      visualized sparse IRBP-positive cells, undetectable by conventional assays, in
      thymi of WT (but not of KO) mice. IRBP message was PCR amplified from these cells
      after microdissection. Thymus transplantation between KO and WT hosts
      demonstrated that this level of expression is functionally relevant and sets the
      threshold of immune (and autoimmune) reactivity. Namely, KO recipients of WT
      thymi generated reduced IRBP-specific responses, and WT recipients of KO thymi
      developed enhanced responses and a highly exacerbated disease. Repertoire culling
      and thymus-dependent CD25+ T cells were implicated in this effect. Thus, uveitis
      susceptible individuals display a detectable and functionally significant
      tolerance to their target antigen, in which central mechanisms play a prominent
      role.

PMID- 14657220
TI  - Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris
      involves molecular recognition by the Dectin-1 beta-glucan receptor.
AB  - Innate immune mechanisms against Pneumocystis carinii, a frequent cause of
      pneumonia in immunocompromised individuals, are not well understood. Using both
      real time polymerase chain reaction as a measure of organism viability and
      fluorescent deconvolution microscopy, we show that nonopsonic phagocytosis of P.
      carinii by alveolar macrophages is mediated by the Dectin-1 beta-glucan receptor
      and that the subsequent generation of hydrogen peroxide is involved in alveolar
      macrophage-mediated killing of P. carinii. The macrophage Dectin-1 beta-glucan
      receptor colocalized with the P. carinii cyst wall. However, blockage of Dectin-1
      with high concentrations of anti-Dectin-1 antibody inhibited binding and
      concomitant killing of P. carinii by alveolar macrophages. Furthermore, RAW 264.7
      macrophages overexpressing Dectin-1 bound P. carinii at a higher level than
      control RAW cells. In the presence of Dectin-1 blockage, killing of opsonized P.
      carinii could be restored through FcgammaRII/III receptors. Opsonized P. carinii
      could also be efficiently killed in the presence of FcgammaRII/III receptor
      blockage through Dectin-1-mediated phagocytosis. We further show that Dectin-1 is
      required for P. carinii-induced macrophage inflammatory protein 2 production by
      alveolar macrophages. Taken together, these results show that nonopsonic
      phagocytosis and subsequent killing of P. carinii by alveolar macrophages is
      dependent upon recognition by the Dectin-1 beta-glucan receptor.

PMID- 14657221
TI  - Leishmania major LACK antigen is required for efficient vertebrate
      parasitization.
AB  - The Leishmania major LACK antigen is a key target of the immune response in
      susceptible BALB/c mice and remains a viable vaccine candidate for human
      leishmaniasis. We describe the genomic organization of the four lack genes in the
      L. major diploid genome together with results of selected lack gene targeting.
      Parasites containing a single lack gene in either the upstream or downstream
      locus grew comparably to wild-type promastigotes in vitro, but failed to
      parasitize BALB/c mice efficiently, even in a T cell-deficient environment. The
      replication of single copy lack mutants as amastigotes was attenuated in
      macrophages in vitro, and parasites failed to increase in numbers in
      immunodeficient mice, despite their persistence over months. Complementation with
      an additional lack copy was sufficient to induce robust lesion development, which
      also occurred using parasites with two lack genes. Conversely, attempts to
      generate lack-null parasites failed, suggesting that LACK is required for
      parasite viability. These data suggest that LACK is critical for effective
      mammalian parasitization and thus represents a potential drug target for
      leishmaniasis.

PMID- 14657222
TI  - Carbon monoxide protects against liver failure through nitric oxide-induced heme
      oxygenase 1.
AB  - Carbon monoxide (CO) and nitric oxide (NO) each have mechanistically unique roles
      in various inflammatory disorders. Although it is known that CO can induce
      production of NO and that NO can induce expression of the cytoprotective enzyme
      heme oxygenase 1 (HO-1), there is no information whether the protective effect of
      CO ever requires NO production or whether either gas must induce expression of HO
      1 to exert its functional effects. Using in vitro and in vivo models of tumor
      necrosis factor alpha-induced hepatocyte cell death in mice, we find that
      activation of nuclear factor kappaB and increased expression of inducible NO are
      required for the protective effects of CO, whereas the protective effects of NO
      require up-regulation of HO-1 expression. When protection from cell death is
      initiated by CO, NO production and HO-1 activity are each required for the
      protective effect showing for the first time an essential synergy between these
      two molecules in tandem providing potent cytoprotection.

PMID- 14657223
TI  - Activation of microglial poly(ADP-ribose)-polymerase-1 by cholesterol breakdown
      products during neuroinflammation: a link between demyelination and neuronal
      damage.
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease in which it has only
      recently been suggested that damage to neuronal structures plays a key role.
      Here, we uncovered a link between the release of lipid breakdown products, found
      in the brain and cerebrospinal fluid (CSF) of MS patients as well as in
      experimental autoimmune encephalomyelitis, and neuronal damage mediated by
      microglial activation. The concentrations of the breakdown product 7
      ketocholesterol detected in the CSF of MS patients were capable of inducing
      neuronal damage via the activation and migration of microglial cells in living
      brain tissue. 7-ketocholesterol rapidly entered the nucleus and activated
      poly(ADP-ribose)-polymerase (PARP)-1, followed by the expression of migration
      regulating integrins CD11a and intercellular adhesion molecule 1. These findings
      reveal a novel mechanism linking demyelination and progressive neuronal damage,
      which might represent an underlying insidious process driving disease beyond a
      primary white matter phenomenon and rendering the microglial PARP-1 a possible
      antiinflammatory therapeutic target.

PMID- 14657224
TI  - Transforming growth factor-beta production and myeloid cells are an effector
      mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte
      mediated tumor immunosurveillance: abrogation prevents tumor recurrence.
AB  - Our previous work demonstrated that cytotoxic T lymphocyte (CTL)-mediated tumor
      immunosurveillance of the 15-12RM tumor could be suppressed by a CD1d-restricted
      lymphocyte, most likely a natural killer (NK) T cell, which produces interleukin
      (IL)-13. Here we present evidence for the effector elements in this suppressive
      pathway. T cell-reconstituted recombination activating gene (RAG)2 knockout (KO)
      and RAG2/IL-4 receptor alpha double KO mice showed that inhibition of
      immunosurveillance requires IL-13 responsiveness by a non-T non-B cell. Such
      nonlymphoid splenocytes from tumor-bearing mice produced more transforming growth
      factor (TGF)-beta, a potent inhibitor of CTL, ex vivo than such cells from naive
      mice, and this TGF-beta production was dependent on the presence in vivo of both
      IL-13 and CD1d-restricted T cells. Ex vivo TGF-beta production was also abrogated
      by depleting either CD11b+ or Gr-1+ cells from the nonlymphoid cells of tumor
      bearing mice. Further, blocking TGF-beta or depleting Gr-1+ cells in vivo
      prevented the tumor recurrence, implying that TGF-beta made by a CD11b+ Gr-1+
      myeloid cell, in an IL-13 and CD1d-restricted T cell-dependent mechanism, is
      necessary for down-regulation of tumor immunosurveillance. Identification of this
      stepwise regulation of immunosurveillance, involving CD1-restricted T cells, IL
      13, myeloid cells, and TGF-beta, explains previous observations on myeloid
      suppressor cells or TGF-beta and provides insights for targeted approaches for
      cancer immunotherapy, including synergistic blockade of TGF-beta and IL-13.

PMID- 14657225
TI  - CD40-deficient, influenza-specific CD8 memory T cells develop and function
      normally in a CD40-sufficient environment.
AB  - Two models have been proposed to explain the requirement for CD40 signaling in
      CD8 T cell responses. The first model suggests that CD4 T cells activate antigen
      presenting cells (APCs) through CD40 signaling (APC licensing). In turn, licensed
      APCs are able to prime naive CD8 T cells. The second model suggests that CD154
      expressing CD4 T cells activate CD40-bearing CD8 T cells directly. Although the
      requirement for CD40 in APC licensing can be bypassed by inflammatory responses
      to pathogens that activate APCs directly, the second model predicts that CD8
      responses to all antigens will be dependent on CD40 signaling. Here we determined
      which model applies to CD8 responses to influenza. We demonstrate that optimal
      CD8 T cell responses to influenza are dependent on CD40 signaling, however both
      primary and secondary responses to influenza require CD40 expression on non-T
      cells. Furthermore, CD40-/- CD8 T cells proliferate and differentiate to the same
      extent as CD40+/+ CD8 T cells in response to influenza, as long as they have
      equal access to CD40+/+ APCs. Thus, CD4 T cells do not activate influenza
      specific CD8 cells directly through CD40 signaling. Instead, these data support
      the classical model, in which CD4 T cells provide help to CD8 T cells indirectly
      by activating APCs through CD40.

PMID- 14657226
TI  - Consolidation radiation after complete remission in Hodgkin's disease following
      six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy:
      is there a need?
AB  - PURPOSE: Combined modality treatment using multidrug chemotherapy (CTh) and
      radiotherapy (RT) is currently considered the standard of care in early stage
      Hodgkin's disease. Its role in advanced stages, however, continues to be debated.
      This study was aimed at evaluating the role of consolidation radiation in
      patients achieving a complete remission after six cycles of doxorubicin,
      bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free
      survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND
      METHODS: Two hundred and fifty-one patients with Hodgkin's disease attending the
      lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996
      received induction chemotherapy with six cycles of ABVD after initial staging
      evaluation. A total of 179 of 251 patients (71%) achieved a complete remission
      after six cycles of ABVD chemotherapy and constituted the randomized population.
      Patients were randomly assigned to receive either consolidation radiation or no
      further therapy. RESULTS: With a median follow-up of 63 months, the 8-year EFS
      and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88%
      and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS
      in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006),
      advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION:
      Our study suggests that the addition of consolidation radiation helps improve the
      EFS and OS in patients achieving a complete remission after six cycles of ABVD
      chemotherapy, particularly in the younger age group and in patients with B
      symptoms and bulky and advanced disease.

PMID- 14657227
TI  - FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal
      cancer: a randomized GERCOR study.
AB  - PURPOSE: In metastatic colorectal cancer, phase III studies have demonstrated the
      superiority of fluorouracil (FU) with leucovorin (LV) in combination with
      irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated
      two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic
      acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm
      B). PATIENTS AND METHODS: Previously untreated patients with assessable disease
      were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2) or dl-LV
      400 mg/m(2) followed by a FU bolus 400 mg/m(2) and 46-hour infusion 2,400 to
      3,000 mg/m(2) every 46 hours every 2 weeks, either with irinotecan 180 mg/m(2) or
      with oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 1. At progression,
      irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm
      B). RESULT: Median survival was 21.5 months in 109 patients allocated to FOLFIRI
      then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI
      (P =.99). Median second progression-free survival (PFS) was 14.2 months in arm A
      versus 10.9 in arm B (P =.64). In first-line therapy, FOLFIRI achieved 56%
      response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54%
      RR and 8.0 months median PFS (P =.26). Second-line FOLFIRI achieved 4% RR and 2.5
      months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In
      first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4
      mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI,
      and grade 3/4 neutropenia and neurosensory toxicity were more frequent with
      FOLFOX6. CONCLUSION: Both sequences achieved a prolonged survival and similar
      efficacy. The toxicity profiles were different.

PMID- 14657228
TI  - Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group
      randomized trial comparing radiotherapy alone with concomitant radiochemotherapy
      in advanced-stage oropharynx carcinoma.
AB  - PURPOSE: We report the 5-year survival and late toxicity results of a randomized
      clinical trial, which showed a 3-year improvement in overall survival and
      locoregional control of stage III or IV oropharynx carcinoma, using concomitant
      radiochemotherapy (arm B), compared with standard radiotherapy (arm A). PATIENTS
      AND METHODS: A total of 226 patients were entered onto a phase III multicenter
      randomized trial comparing radiotherapy alone (70 Gy in 35 fractions; arm A) with
      concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day
      regimen comprising carboplatin and fluorouracil; arm B). Prognostic factors were
      evaluated by univariate and multivariate analysis. Five-year late toxicity was
      evaluated using National Cancer Institute Common Toxicity Criteria for
      neurological toxicity, hearing, taste, mandibula, and teeth damage, and Radiation
      Therapy Oncology Group toxicity criteria for skin, salivary gland, and mucosa.
      RESULTS: Five-year overall survival, specific disease-free survival, and
      locoregional control rates were 22% and 16% (log-rank P =.05), 27% and 15% (P
      =.01), and 48% and 25% (P =.002), in arm B and arm A, respectively. Stage IV,
      hemoglobin level lower than 125 g/L, and standard treatment were independent
      prognostic factors of short survival and locoregional failure by univariate and
      multivariate analysis. One or more grade 3 to 4 complications occurred in 56% of
      the patients in arm B, compared with 30% in arm A (P was not significant).
      CONCLUSION: Concomitant radiochemotherapy improved overall survival and
      locoregional control rates and does not statistically increase severe late
      morbidity. Anemia was the most important prognostic factor for survival in both
      arms.

PMID- 14657229
TI  - Chemotherapy or combined modality treatment: the optimal treatment for Hodgkin's
      disease.

PMID- 14657230
TI  - The need for adverse effects reporting standards in oncology clinical trials.

PMID- 14657231
TI  - L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with
      retrograde actin flow.
AB  - The cell adhesion molecule L1 (L1-CAM) plays critical roles in neurite growth.
      Its cytoplasmic domain (L1CD) binds to ankyrins that associate with the spectrin
      actin network. This paper demonstrates that L1-CAM interactions with ankyrinB
      (but not with ankyrinG) are involved in the initial formation of neurites. In the
      membranous protrusions surrounding the soma before neuritogenesis, filamentous
      actin (F-actin) and ankyrinB continuously move toward the soma (retrograde flow).
      Bead-tracking experiments show that ankyrinB mediates L1-CAM coupling with
      retrograde F-actin flow in these perisomatic structures. Ligation of the L1-CAM
      ectodomain by an immobile substrate induces L1CD-ankyrinB binding and the
      formation of stationary ankyrinB clusters. Neurite initiation preferentially
      occurs at the site of these clusters. In contrast, ankyrinB is involved neither
      in L1-CAM coupling with F-actin flow in growth cones nor in L1-based neurite
      elongation. Our results indicate that ankyrinB promotes neurite initiation by
      acting as a component of the clutch module that transmits traction force
      generated by F-actin flow to the extracellular substrate via L1-CAM.

PMID- 14657232
TI  - GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway.
AB  - The mitochondrial death pathway is triggered in cultured sympathetic neurons by
      deprivation of nerve growth factor (NGF), but the death mechanisms activated by
      deprivation of other neurotrophic factors are poorly studied. We compared
      sympathetic neurons deprived of NGF to those deprived of glial cell line-derived
      neurotrophic factor (GDNF). In contrast to NGF-deprived neurons, GDNF-deprived
      neurons did not die via the mitochondrial pathway. Indeed, cytochrome c was not
      released to the cytosol; Bax and caspase-9 and -3 were not involved;
      overexpressed Bcl-xL did not block the death; and the mitochondrial
      ultrastructure was not changed. Similarly to NGF-deprived neurons, the death
      induced by GDNF removal is associated with increased autophagy and requires
      multiple lineage kinases, c-Jun and caspase-2 and -7. Serine 73 of c-Jun was
      phosphorylated in both NGF- and GDNF-deprived neurons, whereas serine 63 was
      phosphorylated only in NGF-deprived neurons. In many NGF-deprived neurons, the
      ultrastructure of the mitochondria was changed. Thus, a novel nonmitochondrial
      caspase-dependent death pathway is activated in GDNF-deprived sympathetic
      neurons.

PMID- 14657233
TI  - Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and
      epithelia.
AB  - Cell polarity is essential for generating cell diversity and for the proper
      function of most differentiated cell types. In many organisms, cell polarity is
      regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6
      proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid
      larval stages, where they exhibit defects in neuroblast and epithelial cell
      polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail
      to exclude Miranda from the apical cortex; yet, they show normal apical crescents
      of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation.
      Mutant imaginal disc epithelia have defects in apical/basal cell polarity and
      tissue morphology. In addition, we show that aPKC mutants show reduced cell
      proliferation in both neuroblasts and epithelia, the opposite of the lethal giant
      larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly
      suppress most lgl cell polarity and overproliferation phenotypes.

PMID- 14657234
TI  - ADF/cofilin use an intrinsic mode of F-actin instability to disrupt actin
      filaments.
AB  - Proteins in the ADF/cofilin (AC) family are essential for rapid rearrangements of
      cellular actin structures. They have been shown to be active in both the severing
      and depolymerization of actin filaments in vitro, but the detailed mechanism of
      action is not known. Under in vitro conditions, subunits in the actin filament
      can treadmill; with the hydrolysis of ATP driving the addition of subunits at one
      end of the filament and loss of subunits from the opposite end. We have used
      electron microscopy and image analysis to show that AC molecules effectively
      disrupt one of the longitudinal contacts between protomers within one helical
      strand of F-actin. We show that in the absence of any AC proteins, this same
      longitudinal contact between actin protomers is disrupted at the depolymerizing
      (pointed) end of actin filaments but is prominent at the polymerizing (barbed)
      end. We suggest that AC proteins use an intrinsic mechanism of F-actin's internal
      instability to depolymerize/sever actin filaments in the cell.

PMID- 14657235
TI  - Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart
      development and embryonic lethality.
AB  - Tropomodulin1 (Tmod1) caps thin filament pointed ends in striated muscle, where
      it controls filament lengths by regulating actin dynamics. Here, we investigated
      myofibril assembly and heart development in a Tmod1 knockout mouse. In the
      absence of Tmod1, embryonic development appeared normal up to embryonic day (E)
      8.5. By E9.5, heart defects were evident, including aborted development of the
      myocardium and inability to pump, leading to embryonic lethality by E10.5.
      Confocal microscopy of hearts of E8-8.5 Tmod1 null embryos revealed structures
      resembling nascent myofibrils with continuous F-actin staining and periodic dots
      of alpha-actinin, indicating that I-Z-I complexes assembled in the absence of
      Tmod1. Myomesin, a thick filament component, was also assembled normally along
      these structures, indicating that thick filament assembly is independent of
      Tmod1. However, myofibrils did not become striated, and gaps in F-actin staining
      (H zones) were never observed. We conclude that Tmod1 is required for regulation
      of actin filament lengths and myofibril maturation; this is critical for heart
      morphogenesis during embryonic development.

PMID- 14657236
TI  - Espin cross-links cause the elongation of microvillus-type parallel actin bundles
      in vivo.
AB  - The espin actin-bundling proteins, which are the target of the jerker deafness
      mutation, caused a dramatic, concentration-dependent lengthening of LLC-PK1-CL4
      cell microvilli and their parallel actin bundles. Espin level was also positively
      correlated with stereocilium length in hair cells. Villin, but not fascin or
      fimbrin, also produced noticeable lengthening. The espin COOH-terminal peptide,
      which contains the actin-bundling module, was necessary and sufficient for
      lengthening. Lengthening was blocked by 100 nM cytochalasin D. Espin cross-links
      slowed actin depolymerization in vitro less than twofold. Elimination of an actin
      monomer-binding WASP homology 2 domain and a profilin-binding proline-rich domain
      from espin did not decrease lengthening, but made it possible to demonstrate that
      actin incorporation was restricted to the microvillar tip and that bundles
      continued to undergo actin treadmilling at approximately 1.5 s-1 during and after
      lengthening. Thus, through relatively subtle effects on actin
      polymerization/depolymerization reactions in a treadmilling parallel actin
      bundle, espin cross-links cause pronounced barbed-end elongation and, thereby,
      make a longer bundle without joining shorter modules.

PMID- 14657237
TI  - RNA interference and mRNA silencing, 2004: how far will they reach?
AB  - The discoveries of RNA interference and RNA-mediated posttranscriptional gene
      silencing have opened an unanticipated new window on the regulation of gene
      expression as well as a facile and highly effective tool for knocking down gene
      expression in many organisms and cells. In addition, RNA interference and RNA
      silencing may conceivably be exploited for human therapeutics sometime in the
      future, possibly bringing greater clinical impact than have the so far
      disappointing antisense endeavors. This essay summarizes recent developments and
      offers some personalized perspectives, with emphasis on what we do not yet know.

PMID- 14657238
TI  - Differentiation-induced colocalization of the KH-type splicing regulatory protein
      with polypyrimidine tract binding protein and the c-src pre-mRNA.
AB  - We have examined the subcellular localization of the KH-type splicing regulatory
      protein (KSRP). KSRP is a multidomain RNA-binding protein implicated in a variety
      of cellular processes, including splicing in the nucleus and mRNA localization in
      the cytoplasm. We find that KSRP is primarily nuclear with a localization pattern
      that most closely resembles that of polypyrimidine tract binding protein (PTB).
      Colocalization experiments of KSRP with PTB in a mouse neuroblastoma cell line
      determined that both proteins are present in the perinucleolar compartment (PNC),
      as well as in other nuclear enrichments. In contrast, HeLa cells do not show
      prominent KSRP staining in the PNC, even though PTB labeling identified the PNC
      in these cells. Because both PTB and KSRP interact with the c-src transcript to
      affect N1 exon splicing, we examined the localization of the c-src pre-mRNA by
      fluorescence in situ hybridization. The src transcript is present in specific
      foci within the nucleus that are presumably sites of src transcription but are
      not generally perinucleolar. In normally cultured neuroblastoma cells, these src
      RNA foci contain PTB, but little KSRP. However, upon induced neuronal
      differentiation of these cells, KSRP occurs in the same foci with src RNA. PTB
      localization remains unaffected. This differentiation-induced localization of
      KSRP with src RNA correlates with an increase in src exon N1 inclusion. These
      results indicate that PTB and KSRP do indeed interact with the c-src transcript
      in vivo, and that these associations change with the differentiated state of the
      cell.

PMID- 14657239
TI  - P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein
      involved in cell spreading.
AB  - Integrin-mediated cell adhesion stimulates a cascade of signaling pathways that
      control cell proliferation, migration, and survival, mostly through tyrosine
      phosphorylation of signaling molecules. p130Cas, originally identified as a major
      substrate of v-Src, is a scaffold molecule that interacts with several proteins
      and mediates multiple cellular events after cell adhesion and mitogen treatment.
      Here, we describe a novel p130Cas-associated protein named p140Cap (Cas
      associated protein) as a new tyrosine phosphorylated molecule involved in
      integrin- and epidermal growth factor (EGF)-dependent signaling. By affinity
      chromatography of human ECV304 cell extracts on a MBP-p130Cas column followed by
      mass spectrometry matrix-assisted laser desorption ionization/time of flight
      analysis, we identified p140Cap as a protein migrating at 140 kDa. We detected
      its expression in human, mouse, and rat cells and in different mouse tissues.
      Endogenous and transfected p140Cap proteins coimmunoprecipitate with p130Cas in
      ECV304 and in human embryonic kidney 293 cells and associate with p130Cas through
      their carboxy-terminal region. By immunofluorescence analysis, we demonstrated
      that in ECV304 cells plated on fibronectin, the endogenous p140Cap colocalizes
      with p130Cas in the perinuclear region as well as in lamellipodia. In addition
      p140Cap codistributes with cortical actin and actin stress fibers but not with
      focal adhesions. We also show that p140Cap is tyrosine phosphorylated within 15
      min of cell adhesion to integrin ligands. p140Cap tyrosine phosphorylation is
      also induced in response to EGF through an EGF receptor dependent-mechanism.
      Interestingly expression of p140Cap in NIH3T3 and in ECV304 cells delays the
      onset of cell spreading in the early phases of cell adhesion to fibronectin.
      Therefore, p140Cap is a novel protein associated with p130Cas and actin
      cytoskeletal structures. Its tyrosine phosphorylation by integrin-mediated
      adhesion and EGF stimulation and its involvement in cell spreading on matrix
      proteins suggest that p140Cap plays a role in controlling actin cytoskeleton
      organization in response to adhesive and growth factor signaling.

PMID- 14657240
TI  - A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual
      regulation of Bni1 by Bud6 and profilin.
AB  - Formins have conserved roles in cell polarity and cytokinesis and directly
      nucleate actin filament assembly through their FH2 domain. Here, we define the
      active region of the yeast formin Bni1 FH2 domain and show that it dimerizes.
      Mutations that disrupt dimerization abolish actin assembly activity, suggesting
      that dimers are the active state of FH2 domains. The Bni1 FH2 domain protects
      growing barbed ends of actin filaments from vast excesses of capping protein,
      suggesting that the dimer maintains a persistent association during elongation.
      This is not a species-specific mechanism, as the activities of purified mammalian
      formin mDia1 are identical to those of Bni1. Further, mDia1 partially complements
      BNI1 function in vivo, and expression of a dominant active mDia1 construct in
      yeast causes similar phenotypes to dominant active Bni1 constructs. In addition,
      we purified the Bni1-interacting half of the cell polarity factor Bud6 and found
      that it binds specifically to actin monomers and, like profilin, promotes rapid
      nucleotide exchange on actin. Bud6 and profilin show additive stimulatory effects
      on Bni1 activity and have a synthetic lethal genetic interaction in vivo. From
      these results, we propose a model in which Bni1 FH2 dimers nucleate and
      processively cap the elongating barbed end of the actin filament, and Bud6 and
      profilin generate a local flux of ATP-actin monomers to promote actin assembly.

PMID- 14657241
TI  - Translocation of FGF-1 and FGF-2 across vesicular membranes occurs during G1
      phase by a common mechanism.
AB  - The entry of exogenous fibroblast growth factor 2 (FGF-2) to the
      cytosolic/nuclear compartment was studied and compared with the translocation
      mechanism used by FGF-1. To differentiate between external and endogenous growth
      factor, we used FGF-2 modified to contain a farnesylation signal, a CaaX-box.
      Because farnesylation occurs only in the cytosol and nucleoplasm, farnesylation
      of exogenous FGF-2-CaaX was taken as evidence that the growth factor had
      translocated across cellular membranes. We found that FGF-2 translocation
      occurred in endothelial cells and fibroblasts, which express FGF receptors, and
      that the efficiency of translocation was increased in the presence of heparin.
      Concomitantly with translocation, the 18-kDa FGF-2 was N-terminally cleaved to
      yield a 16-kDa form. Translocation of FGF-2 required PI3-kinase activity but not
      transport through the Golgi apparatus. Inhibition of endosomal acidification did
      not prevent translocation, whereas dissipation of the vesicular membrane
      potential completely blocked it. The data indicate that translocation occurs from
      intracellular vesicles containing proton pumps and that an electrical potential
      across the vesicle membrane is required. Translocation of both FGF-1 and FGF-2
      occurred during most of G(1) but decreased shortly before the G(1)-->S
      transition. A common mechanism for FGF-1 and FGF-2 translocation into cells is
      postulated.

PMID- 14657242
TI  - Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from
      membrane rafts to caveolae and subsequent protein kinase C-dependent
      internalization.
AB  - Integrin alpha 2 beta 1 mediates the binding of several epithelial and
      mesenchymal cell types to collagen. The composition of the surrounding plasma
      membrane, especially caveolin-1- and cholesterol-containing membrane structures
      called caveolae, may be important to integrin signaling. On cell surface alpha 2
      beta 1 integrin was located in the raft like membrane domain, rich in GPI
      anchored proteins, rather than in caveolae. However, when antibodies were used to
      generate clusters of alpha 2 beta 1 integrin, they started to move laterally on
      cell surface along actin filaments. During the lateral movement small clusters
      fused together. Finally alpha 2 beta 1 integrin was found inside caveolae and
      subsequently internalized into caveosome-like perinuclear structures. The
      internalization process, unlike cluster formation or lateral redistribution, was
      dependent on protein kinase C alpha activity. Caveolae are known to be highly
      immobile structures and alpha 2 beta 1 integrin clusters represent a previously
      unknown mechanism to activate endocytic trafficking via caveolae. The process was
      specific to alpha 2 beta 1 integrin, because the antibody-mediated formation of
      alpha V integrin clusters activated their internalization in coated vesicles and
      early endosomes. In addition to natural ligands human echovirus-1 (EV1) gains
      entry into the cell by binding to alpha 2 beta 1 and taking advantage of alpha 2
      beta 1 internalization via caveolae.

PMID- 14657243
TI  - WRN helicase and FEN-1 form a complex upon replication arrest and together
      process branchmigrating DNA structures associated with the replication fork.
AB  - Werner Syndrome is a premature aging disorder characterized by genomic
      instability, elevated recombination, and replication defects. It has been
      hypothesized that defective processing of certain replication fork structures by
      WRN may contribute to genomic instability. Fluorescence resonance energy transfer
      (FRET) analyses show that WRN and Flap Endonuclease-1 (FEN-1) form a complex in
      vivo that colocalizes in foci associated with arrested replication forks. WRN
      effectively stimulates FEN-1 cleavage of branch-migrating double-flap structures
      that are the physiological substrates of FEN-1 during replication. Biochemical
      analyses demonstrate that WRN helicase unwinds the chicken-foot HJ intermediate
      associated with a regressed replication fork and stimulates FEN-1 to cleave the
      unwound product in a structure-dependent manner. These results provide evidence
      for an interaction between WRN and FEN-1 in vivo and suggest that these proteins
      function together to process DNA structures associated with the replication fork.

PMID- 14657244
TI  - Telomere attachment, meiotic chromosome condensation, pairing, and bouquet stage
      duration are modified in spermatocytes lacking axial elements.
AB  - During the extended prophase to the meiosis I division, chromosomes assemble
      axial elements (AE) along replicated sister chromatids whose ends attach to the
      inner nuclear membrane (NM) via a specialized conical thickening. Here, we show
      at the EM level that in Sycp3(-/-) spermatocyte chromosomes lack the AE and the
      conical end thickening, but still they attach their telomeres to the inner NM
      with an electron-dense plate that contains T(2)AG(3) repeats. Immunofluorescence
      detected telomere proteins, SCP2, and the meiosis-specific cohesin STAG3 at the
      Sycp3(-/-) telomere. Bouquet stage spermatocytes were approximately threefold
      enriched, and the number of telomere but not centromere signals was reduced to
      the haploid in advanced Sycp3(-/-) spermatocytes, which indicates a special mode
      of homolog pairing at the mammalian telomere. Fluorescence in situ hybridization
      with mouse chromosome 8- and 12-specific subsatellite probes uncovered reduced
      levels of regional homolog pairing, whereas painting of chromosomes 13 revealed
      partial or complete juxtapositioning of homologs; however, condensation of Sycp3(
      /-) bivalents was defective. Electron microscopic analysis of AE-deficient
      spermatocytes revealed that transverse filaments formed short structures
      reminiscent of the synaptonemal complex central region, which likely mediate
      stable homolog pairing. It appears that the AE is required for chromosome
      condensation, rapid exit from the bouquet stage, and fine-tuning of homolog
      pairing.

PMID- 14657245
TI  - Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic
      in human endothelial cells.
AB  - The extracellular matrix (ECM) distinctly modulates membrane type 1-matrix
      metalloproteinase (MT1-MMP) in human endothelial cells (ECs). Herein, ECM
      dependent RhoA activation is shown to regulate MT1-MMP localization and activity
      as well as clathrin-independent internalization in confluent ECs. In this regard,
      caveolae are revealed as the major MT1-MMP endocytic pathway in human ECs. Thus,
      MT1-MMP is present at caveolae with caveolin-1 and both proteins together with
      alpha v beta 3 integrin colocalize at endothelial motility-associated extensions.
      Remarkably, caveolae traffic is required for proper MT1-MMP localization,
      activity, and function in migratory ECs as demonstrated by both treatment with
      caveolae-disrupting agents or selective targeting caveolin-1 expression by
      interference RNA. Thus, caveolae-mediated traffic constitutes a novel mechanism
      for MT1-MMP regulation in ECs during angiogenesis.

PMID- 14657246
TI  - The EF-hand Ca2+-binding protein p22 plays a role in microtubule and endoplasmic
      reticulum organization and dynamics with distinct Ca2+-binding requirements.
AB  - We have reported that p22, an N-myristoylated EF-hand Ca(2+)-binding protein,
      associates with microtubules and plays a role in membrane trafficking. Here, we
      show that p22 also associates with membranes of the early secretory pathway
      membranes, in particular endoplasmic reticulum (ER). On binding of Ca(2+), p22's
      ability to associate with membranes increases in an N-myristoylation-dependent
      manner, which is suggestive of a nonclassical Ca(2+)-myristoyl switch mechanism.
      To address the intracellular functions of p22, a digitonin-based "bulk
      microinjection" assay was developed to load cells with anti-p22, wild-type, or
      mutant p22 proteins. Antibodies against a p22 peptide induce microtubule
      depolymerization and ER fragmentation; this antibody-mediated effect is overcome
      by preincubation with the respective p22 peptide. In contrast, N-myristoylated
      p22 induces the formation of microtubule bundles, the accumulation of ER
      structures along the bundles as well as an increase in ER network formation. An N
      myristoylated Ca(2+)-binding p22 mutant, which is unable to undergo Ca(2+)
      mediated conformational changes, induces microtubule bundling and accumulation of
      ER structures along the bundles but does not increase ER network formation.
      Together, these data strongly suggest that p22 modulates the organization and
      dynamics of microtubule cytoskeleton in a Ca(2+)-independent manner and affects
      ER network assembly in a Ca(2+)-dependent manner.

PMID- 14657247
TI  - Multivesicular body sorting: ubiquitin ligase Rsp5 is required for the
      modification and sorting of carboxypeptidase S.
AB  - The multivesicular body (MVB) sorting pathway provides a mechanism for delivering
      transmembrane proteins into the lumen of the lysosome/vacuole. Recent studies
      demonstrated that ubiquitin modification acts in cis as a signal for the sorting
      of cargoes into this pathway. Here, we present results from a genetic selection
      designed to identify mutants that missort MVB cargoes. This selection identified
      a point mutation in ubiquitin ligase Rsp5 (Rsp5-326). At the permissive
      temperature, this mutant is specifically defective for ubiquitination and sorting
      of the ubiquitin-dependent MVB cargo precursor carboxypeptidase S (pCPS), but not
      ligand-induced ubiquitination of Ste2. A previous study implicated Tul1 as the
      ubiquitin ligase responsible for MVB sorting of pCPS. However, we detected no
      defect in either the sorting or ubiquitination of pCPS in tul1 mutants. We had
      previously shown that Fab1 phosphatidylinositol 3-phosphate 5-kinase is also
      required for MVB sorting of pCPS, but not Ste2. However, our analyses reveal that
      fab1 mutants do not exhibit a defect in ubiquitination of pCPS. Thus, both Rsp5
      and Fab1 play distinct and essential roles in the targeting of biosynthetic MVB
      cargoes. However, whereas Rsp5 seems to be responsible for cargo ubiquitination,
      the precise role for Fab1 remains to be elucidated.

PMID- 14657248
TI  - Reassessing the role and dynamics of nonmuscle myosin II during furrow formation
      in early Drosophila embryos.
AB  - The early Drosophila embryo undergoes two distinct membrane invagination events
      believed to be mechanistically related to cytokinesis: metaphase furrow formation
      and cellularization. Both involve actin cytoskeleton rearrangements, and both
      have myosin II at or near the forming furrow. Actin and myosin are thought to
      provide the force driving membrane invagination; however, membrane addition is
      also important. We have examined the role of myosin during these events in living
      embryos, with a fully functional myosin regulatory light-chain-GFP chimera. We
      find that furrow invagination during metaphase and cellularization occurs even
      when myosin activity has been experimentally perturbed. In contrast, the basal
      closure of the cellularization furrows and the first cytokinesis after
      cellularization are highly dependent on myosin. Strikingly, when ingression of
      the cellularization furrow is experimentally inhibited by colchicine treatment,
      basal closure still occurs at the appropriate time, suggesting that it is
      regulated independently of earlier cellularization events. We have also
      identified a previously unrecognized reservoir of particulate myosin that is
      recruited basally into the invaginating furrow in a microfilament-independent and
      microtubule-dependent manner. We suggest that cellularization can be divided into
      two distinct processes: furrow ingression, driven by microtubule mediated vesicle
      delivery, and basal closure, which is mediated by actin/myosin based
      constriction.

PMID- 14657249
TI  - Gene expression in the normal adult human kidney assessed by complementary DNA
      microarray.
AB  - The kidney is a highly specialized organ with a complex, stereotyped architecture
      and a great diversity of functions and cell types. Because the microscopic
      organization of the nephron, the functional unit of the kidney, has a consistent
      relationship to the macroscopic anatomy of the kidney, knowledge of the
      characteristic patterns of gene expression in different compartments of the
      kidney could provide insight into the functions and functional organization of
      the normal nephron. We studied gene expression in dissected renal lobes of five
      adult human kidneys using cDNA microarrays representing approximately 30,000
      different human genes. Total RNA was isolated from sections of the inner and
      outer cortex, inner and outer medulla, papillary tips, and renal pelvis and from
      glomeruli isolated by sieving. The results revealed unique and highly distinctive
      patterns of gene expression for glomeruli, cortex, medulla, papillary tips, and
      pelvic samples. Immunohistochemical staining using selected antisera confirmed
      differential expression of several cognate proteins and provided histological
      localization of expression within the nephron. The distinctive patterns of gene
      expression in discrete portions of the kidney may serve as a resource for further
      understanding of renal physiology and the molecular and cellular organization of
      the nephron.

PMID- 14657250
TI  - The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted
      to a distinct synaptic vesicle subpopulation.
AB  - Synaptic vesicles (SV) are generated by two different mechanisms, one AP-2
      dependent and one AP-3 dependent. It has been uncertain, however, whether these
      mechanisms generate SV that differ in molecular composition. We explored this
      hypothesis by analyzing the targeting of ZnT3 and synaptophysin both to PC12
      synaptic-like microvesicles (SLMV) as well as SV isolated from wild-type and AP-3
      deficient mocha brains. ZnT3 cytosolic tail interacted selectively with AP-3 in
      cell-free assays. Accordingly, pharmacological disruption of either AP-2- or AP-3
      dependent SLMV biogenesis preferentially reduced synaptophysin or ZnT3 targeting,
      respectively; suggesting that these antigens were concentrated in different
      vesicles. As predicted, immuno-isolated SLMV revealed that ZnT3 and synaptophysin
      were enriched in different vesicle populations. Likewise, morphological and
      biochemical analyses in hippocampal neurons indicated that these two antigens
      were also present in distinct but overlapping domains. ZnT3 SV content was
      reduced in AP-3-deficient neurons, but synaptophysin was not altered in the AP-3
      null background. Our evidence indicates that neuroendocrine cells assemble
      molecularly heterogeneous SV and suggests that this diversity could contribute to
      the functional variety of synapses.

PMID- 14657252
TI  - Direct sorting of the yeast uracil permease to the endosomal system is controlled
      by uracil binding and Rsp5p-dependent ubiquitylation.
AB  - The yeast uracil permease, Fur4p, is downregulated by uracil, which is toxic to
      cells with high permease activity. Uracil promotes cell surface Rsp5p-dependent
      ubiquitylation of the permease, signaling its endocytosis and further vacuolar
      degradation. We show here that uracil also triggers the direct routing of its
      cognate permease from the Golgi apparatus to the endosomal system for
      degradation, without passage via the plasma membrane. This early sorting was not
      observed for a variant permease with a much lower affinity for uracil, suggesting
      that uracil binding is the signal for the diverted pathway. The FUI1-encoded
      uridine permease is similarly sorted for early vacuolar degradation in cells
      exposed to a toxic level of uridine uptake. Membrane proteins destined for
      vacuolar degradation require sorting at the endosome level to the intraluminal
      vesicles of the multivesicular bodies. In cells with low levels of Rsp5p, Fur4p
      can be still diverted from the Golgi apparatus but does not reach the vacuolar
      lumen, being instead missorted to the vacuolar membrane. Correct luminal delivery
      is restored by the biosynthetic addition of a single ubiquitin, suggesting that
      the ubiquitylation of Fur4p serves as a specific signal for sorting to the
      luminal vesicles of the multivesicular bodies. A fused ubiquitin is also able to
      sort some Fur4p from the Golgi to the degradative pathway in the absence of added
      uracil but the low efficiency of this sorting indicates that ubiquitin does not
      itself act as a dominant signal for Golgi-to-endosome trafficking. Our results
      are consistent with a model in which the binding of intracellular uracil to the
      permease signals its sorting from the Golgi apparatus and subsequent
      ubiquitylation ensures its delivery to the vacuolar lumen.

PMID- 14657251
TI  - Meiosis-specific failure of cell cycle progression in fission yeast by mutation
      of a conserved beta-tubulin residue.
AB  - The microtubule cytoskeleton is involved in regulation of cell morphology,
      differentiation, and cell cycle progression. Precisely controlled dynamic
      properties are required for these microtubule functions. To better understand how
      tubulin's dynamics are embedded in its primary sequence, we investigated in vivo
      the consequences of altering a single, highly conserved residue in beta-tubulin
      that lies at the interface between two structural domains. The residue differs
      between the cold-adapted Antarctic fish and temperate animals in a manner that
      suggests a role in microtubule stability. Fungi, like the Antarctic fish, have a
      phenylalanine in this position, whereas essentially all other animals have
      tyrosine. We mutated the corresponding residue in fission yeast to tyrosine.
      Temperature effects were subtle, but time-lapse microscopy of microtubule
      dynamics revealed reduced depolymerization rates and increased stability. Mitotic
      exit signaled by breakdown of the mitotic spindle was delayed. In meiosis,
      microtubules displayed prolonged contact to the cell cortex during horsetail
      movement, followed by completion of meiosis I but frequent asymmetric failure of
      meiosis II spindle formation. Our results indicate that depolymerization dynamics
      modulated through interdomain motion may be important for regulating a subset of
      plus-end microtubule complexes in Schizosaccharomyces pombe.

PMID- 14657253
TI  - Exchangeable chaperone modules contribute to specification of type I and type II
      Hsp40 cellular function.
AB  - Hsp40 family members regulate Hsp70s ability to bind nonnative polypeptides and
      thereby play an essential role in cell physiology. Type I and type II Hsp40s,
      such as yeast Ydj1 and Sis1, form chaperone pairs with cytosolic Hsp70 Ssa1 that
      fold proteins with different efficiencies and carry out specific cellular
      functions. The mechanism by which Ydj1 and Sis1 specify Hsp70 functions is not
      clear. Ydj1 and Sis1 share a high degree of sequence identity in their amino and
      carboxyl terminal ends, but each contains a structurally unique and centrally
      located protein module that is implicated in chaperone function. To test whether
      the chaperone modules of Ydj1 and Sis1 function in the specification of Hsp70
      action, we constructed a set of chimeric Hsp40s in which the chaperone domains of
      Ydj1 and Sis1 were swapped to form YSY and SYS. Purified SYS and YSY exhibited
      protein-folding activity and substrate specificity that mimicked that of Ydj1 and
      Sis1, respectively. In in vivo studies, YSY exhibited a gain of function and,
      unlike Ydj1, could complement the lethal phenotype of sis1 Delta and facilitate
      maintenance of the prion [RNQ+]. Ydj1 and Sis1 contain exchangeable chaperone
      modules that assist in specification of Hsp70 function.

PMID- 14657254
TI  - Hormone-sensitive lipase is required for high-density lipoprotein cholesteryl
      ester-supported adrenal steroidogenesis.
AB  - Steroid hormones are synthesized using cholesterol as precursor, with a
      substantial portion supplied by the selective uptake of lipoprotein-derived
      cholesteryl esters. Adrenals express a high level of neutral cholesteryl ester
      hydrolase activity, and recently hormone-sensitive lipase (HSL) was shown to be
      responsible for most adrenal neutral cholesteryl ester hydrolase activity. To
      determine the functional importance of HSL in adrenal steroidogenesis, adrenal
      cells were isolated from control and HSL-/- mice, and the in vitro production of
      corticosterone was quantified. Results show that, even though adrenal cholesteryl
      ester content was substantially elevated in both male and female HSL-/- mice,
      basal corticosterone production was reduced approximately 50%. The maximum
      corticosterone production induced by dibutyryl cAMP, and lipoproteins was
      approximately 75-85% lower in adrenal cells from HSL-/- mice compared with
      control. There is no intrinsic defect in the conversion of cholesterol into
      steroids in HSL-/- mice. Dibutyryl cAMP-stimulated conversion of high-density
      lipoprotein cholesteryl esters into corticosterone was reduced 97% in HSL-/-
      mice. An increase in low-density lipoprotein receptor expression appears to be
      one of the compensatory mechanisms for cholesterol delivery in HSL-/- mice. These
      findings suggest that HSL is functionally linked to the selective pathway and is
      critically involved in the intracellular processing and availability of
      cholesterol for adrenal steroidogenesis.

PMID- 14657255
TI  - Protein kinase A-induced negative regulation of the corticotropin-releasing
      hormone R1alpha receptor-extracellularly regulated kinase signal transduction
      pathway: the critical role of Ser301 for signaling switch and selectivity.
AB  - Activation of CRH receptors type 1 (CRH-R1) by CRH or urocortin (UCN) leads to
      stimulation of multiple G proteins with consequent effects on diverse signaling
      cascades in a tissue-specific manner. In human myometrium and human embryonic
      kidney (HEK)293 cells, binding of UCN to CRH-R1alpha receptors activates both the
      Gs and Gq, leading to activation of the adenylyl cyclase/protein kinase A (PKA)
      and the phospholipase C/protein kinase C and ERK1/2 signaling pathways,
      respectively. The overall result of these signals is often unpredictable, as
      these two signaling pathways can interact in many cellular systems, with either
      potentiation or inhibition of ERK1/2 activity. In the present studies we
      investigated potential signaling interactions after stimulation of CRH-R1alpha
      receptors in human cultured pregnant myometrial cells or HEK293 cells
      overexpressing recombinant CRH-R1alpha receptors. We found that the adenylyl
      cyclase/PKA pathway has the capacity to markedly decrease UCN-induced ERK1/2
      activation, and that these effects were due in part to the ability of PKA to
      phosphorylate the CRH-R1alpha at position Ser(301) in the third intracellular
      loop. Mutant CRH-R1alpha receptors with substitutions at position Ser(301), which
      is the only potential PKA phosphorylation site, were resistant to PKA-dependent
      phosphorylation and showed altered signaling characteristics, which were
      dependent upon the amino acid substitution at this position. We conclude that
      Ser(301), which is located in the third intracellular loop of CRH-R1alpha, is
      critical for efficient coupling of the receptor to G proteins and to second
      messenger generation. Phosphorylation by PKA prevents maximal coupling of the CRH
      R1alpha to Gq-protein, and thereby reduces activation of ERK 1/2.

PMID- 14657256
TI  - Neural substrates of eyeblink conditioning: acquisition and retention.
AB  - Classical conditioning of the eyeblink reflex to a neutral stimulus that predicts
      an aversive stimulus is a basic form of associative learning. Acquisition and
      retention of this learned response require the cerebellum and associated sensory
      and motor pathways and engage several other brain regions including the
      hippocampus, neocortex, neostriatum, septum, and amygdala. The cerebellum and its
      associated circuitry form the essential neural system for delay eyeblink
      conditioning. Trace eyeblink conditioning, a learning paradigm in which the
      conditioned and unconditioned stimuli are noncontiguous, requires both the
      cerebellum and the hippocampus and exhibits striking parallels to declarative
      memory formation in humans. Identification of the neural structures critical to
      the development and maintenance of the conditioned eyeblink response is an
      essential precursor to the investigation of the mechanisms responsible for the
      formation of these associative memories. In this review, we describe the evidence
      used to identify the neural substrates of classical eyeblink conditioning and
      potential mechanisms of memory formation in critical regions of the hippocampus
      and cerebellum. Addressing a central goal of behavioral neuroscience,
      exploitation of this simple yet robust model of learning and memory has yielded
      one of the most comprehensive descriptions to date of the physical basis of a
      learned behavior in mammals.

PMID- 14657257
TI  - Long-term plasticity of intrinsic excitability: learning rules and mechanisms.
AB  - Spatio-temporal configurations of distributed activity in the brain is thought to
      contribute to the coding of neuronal information and synaptic contacts between
      nerve cells could play a central role in the formation of privileged pathways of
      activity. Synaptic plasticity is not the exclusive mode of regulation of
      information processing in the brain, and persistent regulations of ionic
      conductances in some specialized neuronal areas such as the dendrites, the cell
      body, and the axon could also modulate, in the long-term, the propagation of
      neuronal information. Persistent changes in intrinsic excitability have been
      reported in several brain areas in which activity is elevated during a classical
      conditioning. The role of synaptic activity seems to be a determinant in the
      induction, but the learning rules and the underlying mechanisms remain to be
      defined. We discuss here the role of synaptic activity in the induction of
      intrinsic plasticity in cortical, hippocampal, and cerebellar neurons. Activation
      of glutamate receptors initiates a long-term modification in neuronal
      excitability that may represent a parallel, synergistic substrate for learning
      and memory. Similar to synaptic plasticity, long-lasting intrinsic plasticity
      appears to be bidirectional and to express a certain level of input or cell
      specificity. These nonsynaptic forms of plasticity affect the signal propagation
      in the axon, the dendrites, and the soma. They not only share common learning
      rules and induction pathways with the better-known synaptic plasticity such as
      NMDA receptor dependent LTP and LTD, but also contribute in synergy with these
      synaptic changes to the formation of a coherent engram.

PMID- 14657258
TI  - Spatial learning in the 5-HT1B receptor knockout mouse: selective
      facilitation/impairment depending on the cognitive demand.
AB  - Age-related memory decline is associated with a combined dysfunction of the
      cholinergic and serotonergic systems in the hippocampus and frontal cortex, in
      particular. The 5-HT1B receptor occupies strategic cellular and subcellular
      locations in these structures, where it plays a role in the modulation of ACh
      release. In an attempt to characterize the contribution of this receptor to
      memory functions, 5-HT1B receptor knockout (KO) mice were submitted to various
      behavioral paradigms carried out in the same experimental context (water maze),
      which were aimed at exposing mice to various levels of memory demand. 5-HT1BKO
      mice exhibited a facilitation in the acquisition of a hippocampal-dependent
      spatial reference memory task in the Morris water maze. This facilitation was
      selective of task difficulty, showing thus that the genetic inactivation of the 5
      HT1B receptor is associated with facilitation when the complexity of the task is
      increased, and reveals a protective effect on age-related hippocampal-dependent
      memory decline. Young-adult and aged KO and wild-type (WT) mice were equally able
      to learn a delayed spatial matching-to-sample working memory task in a radial-arm
      water maze with short (0 or 5 min) delays. However, 5-HT1BKO mice, only,
      exhibited a selective memory impairment at intermediate and long (15, 30, and 60
      min) delays. Treatment by scopolamine induced the same pattern of performance in
      wild type as did the mutation for short (5 min, no impairment) and long (60 min,
      impairment) delays. Taken together, these studies revealed a beneficial effect of
      the mutation on the acquisition of a spatial reference memory task, but a
      deleterious effect on a working memory task for long delays. This 5-HT1BKO mouse
      story highlights the problem of the potential existence of "global memory
      enhancers."

PMID- 14657259
TI  - In vitro analog of classical conditioning of feeding behavior in aplysia.
AB  - The feeding behavior of Aplysia californica can be classically conditioned using
      tactile stimulation of the lips as a conditioned stimulus (CS) and food as an
      unconditioned stimulus (US). Moreover, several neural correlates of classical
      conditioning have been identified. The present study extended previous work by
      developing an in vitro analog of classical conditioning and by investigating
      pairing-specific changes in neuronal and synaptic properties. The preparation
      consisted of the isolated cerebral and buccal ganglia. Electrical stimulation of
      a lip nerve (AT4) and a branch of the esophageal nerve (En2) served as the CS and
      US, respectively. Three protocols were used: paired, unpaired, and US alone. Only
      the paired protocol produced a significant increase in CS-evoked fictive feeding.
      At the cellular level, classical conditioning enhanced the magnitude of the CS
      evoked synaptic input to pattern-initiating neuron B31/32. In addition, paired
      training enhanced both the magnitude of the CS-evoked synaptic input and the CS
      evoked spike activity in command-like neuron CBI-2. The in vitro analog of
      classical conditioning reproduced all of the cellular changes that previously
      were identified following behavioral conditioning and has led to the
      identification of several new learning-related neural changes. In addition, the
      pairing-specific enhancement of the CS response in CBI-2 indicates that some
      aspects of associative plasticity may occur at the level of the cerebral sensory
      neurons.

PMID- 14657260
TI  - Basolateral amygdala lesions do not prevent memory of context-footshock training.
AB  - The present studies examined the effects of basolateral amygdala (BLA) lesions
      induced prior to or after context-footshock training on 48-h memory, using
      several retention measures. In experiment 1, male Sprague-Dawley rats with
      bilateral BLA lesions (NMDA, 12.5 mg/mL, 0.2 microL) were given footshock
      training in one compartment of a two-compartment alley. Rats were habituated to
      the alley and 24 h later were given two footshocks in the shock compartment.
      Retention was tested 48 h later, using latency to enter the shock compartment and
      time spent freezing as measures of memory. Two days later, they were tested again
      and received a footshock on each re-entry of the shock compartment prior to
      remaining in the safe compartment for 200 consecutive seconds. The BLA lesions
      did not block retention as assessed by freezing or number of re-entries of the
      shock compartment. In experiment 2, no prior habituation was given, and only one
      footshock was used for the training. BLA lesions did not block retention, as
      indicated by latencies to enter the shock compartment on a 48-h test or by number
      of entries of the shock compartment. Experiment 3 examined the effects of the
      GABAA agonist muscimol infused into the BLA prior to the 48-h retention test. The
      muscimol infusions decreased retention test entrance latencies but did not block
      retention as assessed by the number of subsequent entries of the shock
      compartment. These findings provide additional evidence that an intact BLA is not
      required for the acquisition or retention of context-footshock training.

PMID- 14657262
TI  - Histidine-decarboxylase knockout mice show deficient nonreinforced episodic
      object memory, improved negatively reinforced water-maze performance, and
      increased neo- and ventro-striatal dopamine turnover.
AB  - The brain's histaminergic system has been implicated in hippocampal synaptic
      plasticity, learning, and memory, as well as brain reward and reinforcement. Our
      past pharmacological and lesion studies indicated that the brain's histamine
      system exerts inhibitory effects on the brain's reinforcement respective reward
      system reciprocal to mesolimbic dopamine systems, thereby modulating learning and
      memory performance. Given the close functional relationship between brain
      reinforcement and memory processes, the total disruption of brain histamine
      synthesis via genetic disruption of its synthesizing enzyme, histidine
      decarboxylase (HDC), in the mouse might have differential effects on learning
      dependent on the task-inherent reinforcement contingencies. Here, we investigated
      the effects of an HDC gene disruption in the mouse in a nonreinforced object
      exploration task and a negatively reinforced water-maze task as well as on neo-
      and ventro-striatal dopamine systems known to be involved in brain reward and
      reinforcement. Histidine decarboxylase knockout (HDC-KO) mice had higher
      dihydrophenylacetic acid concentrations and a higher dihydrophenylacetic
      acid/dopamine ratio in the neostriatum. In the ventral striatum,
      dihydrophenylacetic acid/dopamine and 3-methoxytyramine/dopamine ratios were
      higher in HDC-KO mice. Furthermore, the HDC-KO mice showed improved water-maze
      performance during both hidden and cued platform tasks, but deficient object
      discrimination based on temporal relationships. Our data imply that disruption of
      brain histamine synthesis can have both memory promoting and suppressive effects
      via distinct and independent mechanisms and further indicate that these opposed
      effects are related to the task-inherent reinforcement contingencies.

PMID- 14657263
TI  - Emergence of a cue strategy preference on the water maze task in aged C57B6 x SJL
      F1 hybrid mice.
AB  - The effects of age on cue learning, spatial reference memory, and strategy
      preference were assessed in B6 x SJL F1 mice by using the Morris water maze. This
      mouse strain is of particular interest because it is the background strain for a
      common transgenic model of Alzheimer's disease, the Tg2576 mouse, which develops
      plaques and other neurobiological markers of pathology beginning at 8 mo and
      increasing in severity with advanced age. In the current study, 12- and 23-mo-old
      C57B6 x SJL F1 mice were serially trained in cue and place versions of the Morris
      water maze task. At the completion of training, mice received a strategy probe
      test in which place (hidden) and cue (visible) strategies were in competition.
      Cue and spatial learning ability was maintained between 12 and 23 mo of age;
      however, on the strategy preference probe test, the 23-mo-old mice exhibited a
      significant bias toward the selection of a cue strategy. There was no
      relationship between strategy preference in the probe test and spatial learning
      ability, but the 23-mo-old mice did exhibit a strong trend toward shorter
      latencies during visible platform training, possibly reflecting the enhanced
      function of striatal-based neural systems in aging. These data demonstrate that
      23-mo-old C57B6 x SJL F1 mice are capable of effective place learning, but if a
      place strategy is pitted against the use of a cue strategy, the use of a cue
      strategy predominates in the aged mice. The strategy preference observed here may
      reflect an emergence of differential processing in underlying brain circuitry
      with age in the B6 x SJL F1 mouse strain.

PMID- 14657261
TI  - The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion.
AB  - We examined the hypothesis that processes related to DNA recombination and repair
      are involved in learning and memory. Rats received intracerebroventricular
      (i.c.v.) infusions of the antimetabolite 1-beta-D-arabinofuranosylcytosine
      triphosphate (ara-CTP) or its precursor cytosine arabinoside (ara-C) 30 min prior
      to conditioned taste aversion (CTA) training. Both ara-CTP and ara-C caused
      significant impairments in long-term memory (LTM) of CTA. Control experiments
      indicate that the effect of ara-CTP on CTA memory is related to interference with
      learning. Furthermore, as it was previously demonstrated for the protein
      synthesis inhibitor anisomycin, ara-CTP had no effect on CTA memory when it was
      injected 1 h after training. Importantly, although both ara-CTP and anisomycin
      significantly blocked LTM in the task, short-term memory (STM) measured 1 h after
      training was not affected by either of the drugs. Finally, ara-CTP had no effect
      on in vitro transcription, but it did effectively block nonhomologous DNA end
      joining (NHEJ) activity of brain protein extracts. We suggest that DNA ligase
      mediated DNA recombination and repair processes are necessary for the expression
      of LTM in the brain.

PMID- 14657264
TI  - Recognition memory for complex visual discriminations is influenced by stimulus
      interference in rodents with perirhinal cortex damage.
AB  - Rats with perirhinal cortex (PRC), hippocampal, or sham lesions were trained on a
      successive discrimination go/no-go task to examine recognition memory for an
      array of visual objects with varying interference among the objects in the array.
      Rats were trained to recognize a target array consisting of four particular
      objects that could be presented in any one of four possible configurations to
      cover baited food wells. If the four target objects were presented, the rat
      should displace each object to receive food. However, if a novel object replaced
      any one or more of the target objects, then the rat should withhold its response.
      The number of novel objects presented on nonrewarded trials varied from one to
      four. The fewer the number of novel objects in the array, the more interference
      the array shared with the target array, therefore increasing task difficulty. An
      increased number of novel objects should result in less interference with the
      target array and decreased task difficulty. Although accuracy was slightly lower
      in rats with hippocampal lesions compared with controls, the learning of the
      groups was not statistically different. In contrast, rats with PRC lesions were
      significantly impaired in learning compared with both control and hippocampal
      lesioned rats. The results suggest that recognition memory for complex visual
      discriminations is affected by stimulus interference in rodents with PRC damage.

PMID- 14657265
TI  - Impaired visual and odor recognition memory span in patients with hippocampal
      lesions.
AB  - In a recent study, rats with hippocampal lesions performed as well as did
      unoperated rats on an olfactory memory span task, performing approximately 80%
      correct even when the span length reached 24 odors. This finding seems
      potentially at odds with demonstrations that memory-impaired patients typically
      fail tasks in which large amounts of information must be retained. Accordingly,
      we have assessed recognition memory span performance for line drawings of
      objects, designs, and odors in amnesic patients with damage thought to be limited
      to the hippocampal region. The patients were impaired on all three tasks. We
      consider possible explanations for the difference between the findings for humans
      and rats, including the fact that olfactory function is particularly well
      developed in rodents.

PMID- 14657266
TI  - Cardiovascular pharmacology of estradiol metabolites.
AB  - A discussion of the role of endogenous estradiol metabolites in mediating
      important biological actions of estradiol is essentially nonexistent in standard
      textbooks of pharmacology and endocrinology. Indeed, the prevailing view is that
      all biological effects of estradiol are initiated by binding of estradiol per se
      to estrogen receptors and that estradiol metabolites are more or less irrelevant.
      This orthodox view, which is most likely incorrect, is the fundamental premise
      (an estrogen is an estrogen is an estrogen) underlying the design of important
      clinical trials such as the Heart and Estrogen/Progestin Replacement Study and
      the Women's Health Initiative Study. Accumulating data provide convincing
      evidence that some metabolites of estradiol, the major estrogen secreted by human
      ovaries, are biologically active and mediate multiple effects on the
      cardiovascular and renal systems that are largely independent of estrogen
      receptors. More specifically, metabolites of estradiol, particularly
      catecholestradiols and methoxyestradiols, induce multiple estrogen receptor
      independent actions that protect the heart, blood vessels, and kidneys from
      disease. These protective effects are mediated in part by the inhibition of the
      ability of vascular smooth muscle cells, cardiac fibroblasts, and glomerular
      mesangial cells to migrate, proliferate, and secrete extracellular matrix
      proteins, as well as by an improvement in vascular endothelial cell function. The
      purpose of this review is to highlight the cardiovascular and renal pharmacology
      of catecholestradiols and methoxyestradiols. The take home message is simple:
      that when it comes to cardiovascular and renal protection, the concept that all
      estrogenic compounds are created equal may not be true.

PMID- 14657267
TI  - Non-profit publishing: open access and the end of copyright transfer.

PMID- 14657268
TI  - A new kinesin tree.

PMID- 14657269
TI  - ENTH/ANTH proteins and clathrin-mediated membrane budding.
AB  - The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved
      protein module found primarily in proteins that participate in clathrin-mediated
      endocytosis. Structural analyses and ligand-binding studies have shown that a set
      of proteins previously designated as harboring an ENTH domain in fact contain a
      highly similar, yet unique module referred to as an AP180 N-terminal homology
      (ANTH) domain. ENTH and ANTH (E/ANTH) domains bind both inositol phospholipids
      and proteins and contribute to the nucleation and formation of clathrin coats on
      membranes. ENTH domains also function in the development of membrane curvature
      through lipid remodeling during the formation of clathrin-coated vesicles. E/ANTH
      bearing proteins have recently been shown to function with adaptor protein-1 and
      GGA adaptors at the trans-Golgi network, which suggests that E/ANTH domains are
      universal components of the machinery for clathrin-mediated membrane budding.

PMID- 14657270
TI  - Junctional adhesion molecules (JAMs): more molecules with dual functions?
AB  - Junctional adhesion molecules (JAMs) are members of an immunoglobulin subfamily
      expressed by leukocytes and platelets as well as by epithelial and endothelial
      cells, in which they localize to cell-cell contacts and are specifically enriched
      at tight junctions. The recent identification of extracellular ligands and
      intracellular binding proteins for JAMs suggests two functions for JAMs. JAMs
      associate through their extracellular domains with the leukocyte beta2 integrins
      LFA-1 and Mac-1 as well as with the beta1 integrin alpha4beta1. All three
      integrins are involved in the regulation of leukocyte-endothelial cell
      interactions. Through their cytoplasmic domains, JAMs directly associate with
      various tight junction-associated proteins including ZO-1, AF-6, MUPP1 and the
      cell polarity protein PAR-3. PAR-3 is part of a ternary protein complex that
      contains PAR-3, atypical protein kinase C and PAR-6. This complex is highly
      conserved through evolution and is involved in the regulation of cell polarity in
      organisms from Caenorhabditis elegans and Drosophila to vertebrates. These
      findings point to dual functions for JAMs: they appear to regulate both
      leukocyte/platelet/endothelial cell interactions in the immune system and tight
      junction formation in epithelial and endothelial cells during the acquisition of
      cell polarity.

PMID- 14657272
TI  - Cell behaviour on micropatterned substrata: limits of extracellular matrix
      geometry for spreading and adhesion.
AB  - Cell adhesion, spreading and migration require the dynamic formation and
      dispersal of contacts with the extracellular matrix (ECM). In vivo, the number,
      availability and distribution of ECM binding sites dictate the shape of a cell
      and determine its mobility. To analyse the geometrical limits of ECM binding
      sites required for cell attachment and spreading, we used microcontact printing
      to produce regular patterns of ECM protein dots of defined size separated by
      nonadhesive regions. Cells cultured on these substrata adhere to and spread on
      ECM regions as small as 0.1 microm2, when spacing between dots is less than 5
      microm. Spacing of 5-25 microm induces a cell to adapt its shape to the ECM
      pattern. The ability to spread and migrate on dots > or =1 microm2 ceases when
      the dot separation is > or =30 microm. The extent of cell spreading is directly
      correlated to the total substratum coverage with ECM-proteins, but irrespective
      of the geometrical pattern. An optimal spreading extent is reached at a surface
      coating above 15%. Knowledge of these geometrical limits is essential for an
      understanding of cell adhesion and migration, and for the design of artificial
      surfaces that optimally interact with cells in a living tissue.

PMID- 14657271
TI  - NF-kappaB signaling in lymphocytes: a new cast of characters.
AB  - Cell-surface antigen receptors on B and T lymphocytes are complex, multisubunit
      assemblies that must recruit several accessory proteins and activate multiple
      signaling pathways in order to illicit a proper immune response. One pathway
      culminates in the activation of specific protein kinase C (PKC) isoforms, which
      is necessary for the ultimate activation of the NF-kappaB transcription factor.
      Since NF-kappaB plays a crucial role in the adaptive immune response (e.g. in
      lymphocyte proliferation and cytokine production), it is important to understand
      the molecular mechanisms by which NF-kappaB is regulated. Nevertheless, the
      connection between PKC activation and NF-kappaB has remained a mystery that has
      now been at least partly solved. Recent findings implicate a new scaffolding
      protein, Bimp3/CARMA1/CARD11, as a key factor in bridging PKC activation with the
      downstream activation of Bcl10 and MALT1, which ultimately stimulates NF-kappaB.
      Since some of these signaling components are lymphocyte specific, therapeutic
      agents that block this pathway could blunt the inappropriate proliferation of
      lymphocytes associated with certain inflammatory and neoplastic disorders.
      Alternatively, agents that specifically augment this pathway, thereby enhancing
      immune function in immunodeficiency, may be developed.

PMID- 14657273
TI  - N-RAP scaffolds I-Z-I assembly during myofibrillogenesis in cultured chick
      cardiomyocytes.
AB  - N-RAP is a muscle-specific protein with an N-terminal LIM domain (LIM), C
      terminal actin-binding super repeats homologous to nebulin (SR) and nebulin
      related simple repeats (IB) in between the two. Based on biochemical data,
      immunofluorescence analysis of cultured embryonic chick cardiomyocytes and the
      targeting and phenotypic effects of these individual GFP-tagged regions of N-RAP,
      we proposed a novel model for the initiation of myofibril assembly in which N-RAP
      organizes alpha-actinin and actin into the premyofibril I-Z-I complexes. We
      tested the proposed model by expressing deletion mutants of N-RAP (i.e.
      constructs containing two of the three regions of N-RAP) in chick cardiomyocytes
      and observing the effects on alpha-actinin and actin organization into mature
      sarcomeres. Although individually expressing either the LIM, IB, or SR regions of
      N-RAP inhibited alpha-actinin assembly into Z-lines, expression of either the LIM
      IB fusion or the IB-SR fusion permitted normal alpha-actinin organization. In
      contrast, the LIM-SR fusion (LIM-SR) inhibited alpha-actinin organization into Z
      lines, indicating that the IB region is critical for Z-line assembly. While
      permitting normal Z-line assembly, LIM-IB and IB-SR decreased sarcomeric actin
      staining intensity; however, the effects of LIM-IB on actin assembly were
      significantly more severe, as estimated both by morphological assessment and by
      quantitative measurement of actin staining intensity. In addition, LIM-IB was
      consistently retained in mature Z-lines, while mature Z-lines without significant
      IB-SR incorporation were often observed. We conclude that the N-RAP super repeats
      are essential for organizing actin filaments during myofibril assembly in
      cultured embryonic chick cardiomyocytes, and that they also play an important
      role in removal of the N-RAP scaffold from the completed myofibrillar structure.
      This work strongly supports the N-RAP scaffolding model of premyofibril assembly.

PMID- 14657274
TI  - The S. cerevisiae HtrA-like protein Nma111p is a nuclear serine protease that
      mediates yeast apoptosis.
AB  - The yeast S. cerevisiae can undergo programmed cell death that exhibits the
      typical cellular markers of apoptosis. The mammalian HtrA2 protein was recently
      reported to mediate apoptosis in a serine-protease-dependent manner owing to its
      ability to antagonise the inhibitor of apoptosis protein XIAP. Here, we report
      the identification and characterisation of the S. cerevisiae HtrA-like protein,
      which we termed Nma111p (for nuclear mediator of apoptosis), as a mediator of
      yeast apoptosis. Nma111p is a nuclear protein that, under cellular stress
      conditions (i.e. at elevated temperature or after induction of apoptosis by
      H2O2), tends to aggregate inside the nucleus without its expression level being
      upregulated, suggesting that aggregation of Nma111p is correlated to its death
      mediating character. Nma111p belongs to the HtrA family of serine proteases and
      its pro-apoptotic activity depends on its serine-protease activity. Yeast cells
      that lack Nma111p survive better at 50 degrees C than wild-type cells and the
      cells show no apoptotic hallmarks, such as chromatin condensation and
      fragmentation, or accumulation of reactive oxygen species, after the induction of
      apoptosis by H2O2. By contrast, overexpression of Nma111p enhances apoptotic-like
      cell death. Therefore, Nma111p, like its mammalian homologue HtrA2, mediates
      apoptosis.

PMID- 14657275
TI  - Hyaluronan-oligosaccharide-induced transcription of metalloproteases.
AB  - Activated dendritic epidermal Langerhans cells and metastatic tumour cells share
      many properties. Both cell types can invade the surrounding tissue, enter the
      lymphatic system and travel to regional lymph nodes. We have recently shown that
      fragments of the extracellular matrix component hyaluronan, which are typically
      produced at sites of inflammation, can activate dendritic cells. Upon activation,
      dendritic cells upregulate expression of matrix metalloproteases (MMPs). These
      observations prompted us to investigate whether exposure to hyaluronan fragments
      also induces MMP expression in tumour cells. Here, we report that MMP-9, MMP-13
      and urokinase plasminogen activator are upregulated in murine 3LL tumour cells
      after exposure to mixed-size hyaluronan. Similarly upregulated MMP-9 and MMP-13
      expression was observed in primary fibroblasts. By using size-fractionated
      hyaluronan preparations, we show that the enhanced expression of MMP-9 and MMP-13
      is only induced by small hyaluronan (HA) fragments. Although our data suggest
      that HA-fragment-induced MMP-9 and MMP-13 expression is receptor mediated, they
      rule out an involvement of the hyaluronan receptors CD44, RHAMM/IHAP and TLR-4.
      Finally, we show that HA fragment-induced MMP-9 transcription is mediated via NF
      kappa B. Our results suggest that the metastasis-associated HA degradation in
      tumours might promote invasion by inducing MMP expression.

PMID- 14657276
TI  - STAT3 is enriched in nuclear bodies.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a transcription
      factor that is involved in a variety of biological functions. It is essential for
      the signal transduction of interleukin-6 (IL-6) and related cytokines. In
      response to IL-6 stimulation STAT3 becomes phosphorylated and translocates into
      the nucleus where it binds to enhancer sequences of target genes. We found that
      activated STAT3 is enriched in dot-like structures within the nucleus, which we
      termed STAT3 nuclear bodies. To examine the dynamics of STAT3 nuclear body
      formation, a fusion protein of STAT3 and yellow fluorescent protein (YFP) was
      constructed. Studies in living cells have shown that the appearance of STAT3
      nuclear bodies is transient, correlating with the timecourse of tyrosine
      phosphorylation of STAT3. Furthermore, we show by fluorescence recovery after
      photobleaching (FRAP) analysis that STAT3 within nuclear bodies consists of a
      highly mobile and an immobile fraction. Colocalization studies provided evidence
      that these bodies are accompanied with CREB binding protein (CBP) and acetylated
      histone H4, which are markers for transcriptionally active chromatin. Moreover,
      STAT3 nuclear bodies in HepG2 cells are not colocalized with promyelocytic
      leukemia oncoprotein (PML)-containing bodies; neither is a sumoylation of
      activated STAT3 detectable. Taken together, our data suggest that STAT3 nuclear
      bodies are either directly involved in active gene transcription or they serve as
      reservoirs of activated STAT3.

PMID- 14657278
TI  - The pot1+ homologue in Aspergillus nidulans is required for ordering mitotic
      events.
AB  - Orderly progression through mitosis is essential to reduce segregation errors in
      the cell's genetic material. We have used a cytological screen to identify a
      mutant that progresses through mitosis aberrantly and have cloned the
      complementing gene, nimU, which encodes a protein related to Pot1 and other
      telomere end-binding proteins. We show that loss of nimU function leads to
      premature mitotic spindle elongation, premature mitotic exit, errors in
      chromosome segregation, and failure to delay mitotic exit under conditions that
      normally evoke the mitotic spindle checkpoint response. Whereas premature mitotic
      exit is dependent upon anaphase promoting complex function, premature spindle
      elongation is not. We conclude that nimU is constitutively required for orderly
      mitotic progression under normal growth conditions and also required for the
      conditional mitotic spindle checkpoint response.

PMID- 14657277
TI  - RNA interference of valosin-containing protein (VCP/p97) reveals multiple
      cellular roles linked to ubiquitin/proteasome-dependent proteolysis.
AB  - We have used RNA interference (RNAi) to examine the functional relationship
      between valosin-containing protein (VCP/p97/Cdc48p/TER94) ATPase and the
      ubiquitin-proteasome system (UPS) in Drosophila S2 and human HeLa cells. In both
      cell types, RNAi of VCP (and, to a lesser extent, of certain VCP-interacting
      proteins) caused significant accumulation of high-molecular-weight conjugates of
      ubiquitin, an indication of inhibited UPS function. However, decreased VCP levels
      did not directly inhibit proteasome activity. In HeLa cells, polyubiquitinated
      proteins accumulated as dispersed aggregates rather than as single aggresomes,
      even in the presence of proteasome inhibitors, which normally promote aggresome
      formation. RNAi of VCP caused extensive vacuolization of the cytoplasm, and
      proteasome inhibitors exaggerated this feature. RNAi of VCP had little effect on
      S2 cell proliferation but blocked cell-cycle progression and induced mitotic
      abnormalities and apoptosis in HeLa cells. These results indicate that VCP plays
      an important general role in mediating the function of the UPS, probably by
      interacting with potential proteasome substrates before they are degraded by the
      proteasome.

PMID- 14657279
TI  - FAK promotes organization of fibronectin matrix and fibrillar adhesions.
AB  - Targeted disruption of the focal adhesion kinase (FAK) gene in mice is lethal at
      embryonic day 8.5 (E8.5). Vascular defects in FAK-/- mice result from the
      inability of FAK-deficient endothelial cells to organize themselves into vascular
      network. We found that, although fibronectin (FN) levels were similar, its
      organization was less fibrillar in both FAK-/- endothelial cells and mesoderm of
      E8.5 FAK-/- embryos, as well as in mouse embryonic fibroblasts isolated from
      mutant embryos. FAK catalytic activity, proline-rich domains, and location in
      focal contacts were all required for proper allocation and patterning of FN
      matrix. Cells lacking FAK in focal adhesions fail to translocate supramolecular
      complexes of integrin-bound FN and focal adhesion proteins along actin filaments
      to form mature fibrillar adhesions. Taken together, our data suggest that proper
      FN allocation and organization are dependent on FAK-mediated remodeling of focal
      adhesions.

PMID- 14657280
TI  - Lamellipodium extension and cadherin adhesion: two cell responses to cadherin
      activation relying on distinct signalling pathways.
AB  - Cell adhesion molecules of the cadherin family contribute to the regulation of
      cell shape and fate by mediating strong intercellular adhesion through Ca2+
      dependent interaction of their ectodomain and association of their cytoplasmic
      tail to actin. However, the mechanisms co-ordinating cadherinmediated adhesion
      with the reorganization of the actin cytoskeleton remain elusive. Here, the
      formation of de novo contacts was dissected by spreading cells on a highly active
      N-cadherin homophilic ligand. Cells responded to N-cadherin activation by
      extending lamellipodium and organizing cadherin-catenin complexes and actin
      filaments in cadherin adhesions. Lamellipodium protrusion, associated with actin
      polymerization at the leading edge sustained the extension of cadherin contacts
      through a phosphoinositide 3-kinase (PI 3-kinase)-Rac1 pathway. Cadherin
      adhesions were formed by PI 3-kinase-independent, Rac1-dependent co-recruitment
      of adhesion complexes and actin filaments. The expression and localization of
      p120 at the plasma membrane, associated with an increase in membrane-associated
      Rac1 was required for both cell responses, consistent with a major role of p120
      in signalling pathways initiated by cadherin activation and contributing to Rac1
      dependent contact extension and maturation. These results provide additional
      information on the mechanisms by which cadherin coordinates adhesion with dynamic
      changes in the cytoskeleton to control cell shape and intercellular junction
      organization.

PMID- 14657281
TI  - Dendritic cells as host cells for the promastigote and amastigote stages of
      Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic
      cell maturation.
AB  - In their mammalian hosts, Leishmania are obligate intracellular parasites that
      mainly reside in macrophages. They are also phagocytosed by dendritic cells
      (DCs), which play decisive roles in the induction and shaping of T cell-dependent
      immune responses. Little is known about the role of DCs in the Leishmania life
      cycle. Here, we examined the ability of mouse bone marrow-derived DCs to serve as
      hosts for L. amazonensis. Both infective stages of Leishmania (metacyclic
      promastigotes and amastigotes) could be phagocytosed by DCs, regardless of
      whether they had previously been experimentally opsonized with either the
      complement C3 component or specific antibodies. Parasites could survive and even
      multiply in these cells for at least 72 hours, within parasitophorous vacuoles
      displaying phagolysosomal characteristics and MHC class II and H-2M molecules. We
      then studied the degree of maturation reached by infected DCs according to the
      parasite stage internalised and the type of opsonin used. The cell surface
      expression of CD24, CD40, CD54, CD80, CD86, OX40L and MHC class II molecules was
      barely altered following infection with unopsonized promastigotes or amastigotes
      from nude mice or with C3-coated promastigotes. Even 69 hours post-phagocytosis,
      a large proportion of infected DCs remained phenotypically immature. In contrast,
      internalisation of antibody-opsonized promastigotes or amastigotes induced DCs to
      mature rapidly, as shown by the over-expression of costimulatory, adhesion and
      MHC class II molecules. Thus, in the absence of specific antibodies (e.g. shortly
      after infecting naive mammals), infected DCs may remain immature or semi-mature,
      meaning that they are unable to elicit an efficient anti-Leishmania T cell
      response. Absence of DC maturation or delayed/incomplete DC maturation could thus
      be beneficial for the parasites, allowing their establishment and amplification
      before the onset of immune responses.

PMID- 14657283
TI  - Nuclear medicine technology state of the union.

PMID- 14657284
TI  - Technical overview of brain SPECT imaging: improving acquisition and processing
      of data.
AB  - The purpose of this article is to give a basic understanding of imaging setup,
      postprocessing procedures, and anatomy for brain SPECT. After reading the
      article, the nuclear medicine professional should be able to describe the normal
      anatomy of the brain; the localization of radiopharmaceutical complexes within
      the brain; good techniques for image acquisition; and the concepts of filtered
      backprojection, smoothing filters, and attenuation correction in reconstruction.

PMID- 14657286
TI  - Measurement of 18F-FDG concentrations in blood samples: comparison of direct
      calibration and standard solution methods.
AB  - OBJECTIVE: The purpose of this study was to compare the accuracy and reliability
      of 2 well counter methods for measuring the activity concentration of (18)F-FDG
      in blood samples. METHODS: Three to 5 blood samples from 154 patient studies were
      weighed and measured in a well counter. The (18)F-FDG activity concentration was
      derived using, first, a direct calibration factor to convert measured well
      counter readings into activity concentration and, second, a comparison of
      measured counts with those of a specified standard solution. RESULTS: The ratio
      between the activity concentration results of the 2 methods was 0.996 +/- 0.033,
      indicating that the methods provided equal results. CONCLUSION: Because the
      standard solution method is more prone to human error, less reproducible, and
      more labor intensive, preference should be given to the direct calibration
      method.

PMID- 14657285
TI  - Nuclear medicine and infection detection: the relative effectiveness of imaging
      with 111In-oxine-, 99mTc-HMPAO-, and 99mTc-stannous fluoride colloid-labeled
      leukocytes and with 67Ga-citrate.
AB  - With a current annual mortality rate of around 35% worldwide, infection remains a
      significant concern, and the diagnosis and localization of infectious foci is an
      important health issue. As an established infection-imaging modality, nuclear
      medicine plays a vital health-care role in the diagnosis and subsequent effective
      treatment of this condition. Despite the development of several newer
      radiopharmaceuticals, (67)Ga and leukocyte imaging procedures have maintained
      their established place for infection. Several techniques in nuclear medicine
      significantly aid infection diagnosis, including imaging with (111)In-oxine-,
      (99m)Tc-hexamethylpropyleneamine oxime-, and (99m)Tc-stannous fluoride colloid
      labeled leukocytes and with (67)Ga-citrate. Each radiopharmaceutical has specific
      advantages and disadvantages that make it suitable to diagnose different
      infectious processes (e.g., soft-tissue sepsis, inflammatory bowel disease,
      osteomyelitis, occult fever, fever of unknown origin, and infections commonly
      found in immunocompromised patients). After finishing this article, the reader
      should be able to identify the properties of an ideal radiopharmaceutical for
      infection imaging, list a range of available infection-imaging
      radiopharmaceuticals, compare the relative results of a range of
      radiopharmaceuticals used internationally to detect infection in the body,
      understand several common infectious processes that can be diagnosed using
      nuclear medicine techniques, and select an appropriate radiopharmaceutical to
      image a range of infectious processes.

PMID- 14657287
TI  - 18F protection issues: human and gamma-camera considerations.
AB  - OBJECTIVE: Two main issues in protecting radiation workers and the general public
      from (18)F radiation-distance from and lead shielding for an (18)F source-were
      investigated. We also examined the effect of an (18)F source on the counting rate
      of a neighboring gamma-camera. METHODS: The dose rates of an (18)F vial and a
      water-filled cylinder were measured using an ionization chamber at different
      distances with or without lead shielding. In addition, the counting rates of
      gamma-cameras in the presence of the (18)F cylinder were measured with different
      detector orientations, distances, and energy windows. RESULTS: The dose rate of a
      point or an extended source in air was proportional to the inverse square of the
      distance from the source. At 2 m, the dose rate for a 370-MBq (18)F source was
      less than 20 micro Gy in any single hour, which is the limit for unrestricted
      areas. The dose rate with 0.318-cm-thick lead shielding decreased to about 60%,
      and that with 5.08-cm-thick lead shielding decreased to about 4%; these rates
      were higher than those estimated using the narrow-beam attenuation formula. The
      scattered photons and characteristic x-rays from the lead brick and surrounding
      structures may have contributed to this result. The decrease in dose rate
      resulting from a 33% increase in distance was similar to the effect from
      shielding the source with 0.318-cm-thick lead. At 3 m from a 185-MBq (18)F
      source, the counting rate in the (99m)Tc window of an Orbiter camera was about
      120,000/min when the detector faced the source. This rate was comparable to that
      of a typical (99m)Tc clinical study ( approximately 200,000/min). Only when the
      distance was increased to 11 m and the detector did not face the source did the
      counting rate decrease to the background level (3,234/min). The counting rate
      also depended on the energy window of the gamma-camera. On a Vertex camera, the
      counting rate of (18)F in the (99m)Tc window versus that in the (201)Tl (or
      (67)Ga) window was 1:1.7 (or 1:2.7). CONCLUSION: (18)F dose rate can be
      significantly reduced with distance. Lead shielding is not as effective as was
      predicted. (18)F sources should be kept substantial distances away from gamma
      cameras to avoid contamination of image quality.

PMID- 14657288
TI  - Administered activity optimization in 99mTc-MAG3 renography for adults.
AB  - OBJECTIVE: The objective of this work was to determine the minimum administered
      activity of (99m)Tc-mercaptoacetyltriglycine (MAG3) needed both to estimate
      effective renal plasma flow (ERPF) with adequate precision and to obtain good
      image quality. METHODS: Three groups of 10 patients each were injected with 45,
      71, or 132 MBq of MAG3. Renograms and perfusion and clearance images were
      obtained. The age, sex, and weight of the patients; the labeling yield; the mean
      count and counting rate 2 min after injection; the kidney-to-background and
      cortex-to-background ratios; the uptake time from the renograms; the percentage
      of the injected activity 2 min after injection in the left and right kidneys
      (A2(LK) and A2(RK), respectively); and the ERPF for both kidneys were obtained
      and analyzed. Discriminant analysis of image quality was used to select the
      variables that most affected image quality. The selected variables were studied
      among activity groups to optimize the amount of activity administered in these
      studies. RESULTS: Precision in ERPF assessment did not significantly differ among
      administered activity levels (P = 0.824). The SDs of the ERPF were +/-1.5 for 132
      MBq, +/-1.7 for 71 MBq, and +/-2.0 for 45 MBq. The labeling yield, the ratios of
      counts in the left and right kidneys to the background and in the left and right
      cortices to the background, and A2(LK) and A2(RK) were the only variables that
      provided a significant discriminant function for image quality. The only variable
      that significantly differed with the variation in administered activity was the
      ratio of counts in the right kidney to the background (P = 0.026), most likely
      because of the labeling yield. CONCLUSION: A 45-MBq activity is sufficient to
      guarantee good image quality and adequate precision in ERPF determination from
      the time-activity curve, provided the labeling yield is kept high.

PMID- 14657289
TI  - Performance and responsibility guidelines for the nuclear medicine technologist
      (revision 2003).

PMID- 14657291
TI  - NMTCB report.

PMID- 14657292
TI  - Technologists news.

PMID- 14657295
TI  - How can superparamagnetic iron oxides be used to monitor disease and treatment?

PMID- 14657300
TI  - Dementia: one of the greatest fears of aging.

PMID- 14657301
TI  - National Institute of Biomedical Imaging and Bioengineering: poised for the
      future.

PMID- 14657302
TI  - The science and ethics of cloning: what physicians need to know.

PMID- 14657303
TI  - Speech delay in children: a functional MR imaging study.
AB  - PURPOSE: To determine if children with speech delay who have been sedated have
      patterns of activation to passive language paradigms that are different than
      those of children with normal speech. MATERIALS AND METHODS: Seventeen children
      with speech delay (age range, 2-7 years; mean, 4.0 years) and 35 age-matched
      children with normal speech (age range, 2-8 years; mean, 4.2 years) were
      evaluated. The subjects in the control group were selected from patients referred
      for conventional magnetic resonance (MR) imaging. All children had absence of
      auditory impairment or mental retardation, and MR findings indicated that brain
      structure was normal. Sedation was achieved with pentobarbital (3-5 mg/kg) or
      chloral hydrate (75 mg/kg). Functional MR imaging was performed with a single
      shot echo-planar blood oxygen-level-dependent technique and a passive block
      paradigm, in which the child listened to his or her mother's prerecorded voice.
      Statistical postprocessing of functional MR images was performed with the t test
      and cluster detection methods. Comparison between groups was performed depending
      on the type of data with a nonparametrical Mann-Whitney test, parametrical t
      test, or Fisher exact test. RESULTS: Five (83%) of the six children older than 3
      years with speech delay had lateralized activation of functional MR imaging
      signal in the right hemisphere. Ten (71%) of 14 age-matched patients with normal
      speech had activation in the left hemisphere when exposed to the same passive
      listening tasks. When these groups were compared, this difference was
      statistically significant. (P =.036). No statistically significant lateralization
      was seen across all age groups in children with activation. CONCLUSION: Children
      older than 3 years with speech delay have activation in the right hemisphere more
      frequently than children older than 3 years with normal speech, who often have
      the expected finding of activation in the left hemisphere.

PMID- 14657304
TI  - The molar tooth sign.

PMID- 14657305
TI  - Comparisons of regional white matter diffusion in healthy neonates and adults
      performed with a 3.0-T head-only MR imaging unit.
AB  - PURPOSE: To evaluate the normal brains of adults and neonates for regional and
      age-related differences in apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA). MATERIALS AND METHODS: Eight healthy adults and 20 healthy
      neonates were examined with a 3.0-T head-only magnetic resonance (MR) imaging
      unit by using a single-shot diffusion-tensor sequence. Trace ADC maps, FA maps,
      directional maps of the putative directions of white matter (WM) tracts, and
      fiber-tracking maps were obtained. Regions of interest-eight in WM and one in
      gray matter (GM)-were predefined for the ADC and FA measurements. The Student t
      test was used to compare FA and ADC between adults and neonates, whereas the
      Tukey multiple-comparison test was used to compare FA and ADC in different brain
      regions in the adult and neonate groups. RESULTS: A global elevation in ADC (P
      <.001) in both GM and WM and a reduction in FA (P <.001) in WM were observed in
      neonates as compared with these values in adults. In addition, significant
      regional variations in FA and ADC were observed in both groups. Regional
      variations in FA and ADC were less remarkable in adults, whereas neonates had
      consistently higher FA values and lower ADC values in the central WM as compared
      with these values in the peripheral WM. Fiber tracking revealed only major WM
      tracts in the neonates but fibers extending to the peripheral WM in the adults.
      CONCLUSION: There were regional differences in FA and ADC values in the neonates;
      such variations were less remarkable in the adults.

PMID- 14657306
TI  - Regional brain atrophy rate predicts future cognitive decline: 6-year
      longitudinal MR imaging study of normal aging.
AB  - PURPOSE: To determine if medial temporal lobe (MTL) atrophy rate, assessed by
      using an automated procedure over the initial time interval of a 6-year, three
      time-point longitudinal study, is predictive of future memory decline. MATERIALS
      AND METHODS: Healthy elderly subjects (age, >60 years) were administered a
      comprehensive battery of neuropsychometric tests and underwent magnetic resonance
      (MR) imaging at baseline and two or more follow-up examinations. The rate of
      brain atrophy between the baseline and first follow-up examinations was assessed
      by using an automated procedure that included spatial coregistration of the two
      images and regional brain boundary shift analysis. At final observation, the 45
      subjects were separated into a group of those who did and a group of those who
      did not show objective evidence of cognitive decline. A forward stepwise logistic
      regression model was used to identify variables that predicted decline. RESULTS:
      Thirty-two subjects remained healthy, and 13 showed cognitive decline. Among
      subjects who showed cognitive decline, six declined after the second observation.
      MTL atrophy rate, through its interactions with sex and age, was the most
      significant predictor of decline. The overall accuracy of prediction was 89% (in
      40 of 45 subjects), with 91% specificity (in 29 of 32 subjects) and 85%
      sensitivity (in 11 of 13 subjects). CONCLUSION: Among healthy elderly
      individuals, increased MTL atrophy rate appears to be predictive of future memory
      decline.

PMID- 14657307
TI  - Low-field-strength MR imaging of failed hip arthroplasty: association of femoral
      periprosthetic signal intensity with radiographic, surgical, and pathologic
      findings.
AB  - PURPOSE: To investigate the association between periprosthetic signal intensity
      at low-field-strength magnetic resonance (MR) imaging after failed hip
      arthroplasty and radiographic, surgical, and pathologic findings. MATERIALS AND
      METHODS: The study group comprised 22 consecutive women who underwent hip
      arthroplasty (mean age, 62 years; age range, 35-74 years). All patients underwent
      MR imaging prior to revision surgery. Coronal fast short inversion time inversion
      recovery (STIR) images and spin-echo T1-weighted images were obtained with a 0.5
      T MR imaging unit before and after administration of contrast material. The
      periprosthetic region was divided into the seven femoral Gruen zones. Two
      observers retrospectively analyzed signal intensity patterns. Association of
      signal intensity patterns with radiographic, surgical, and pathologic findings
      was determined with chi2 analysis and generalized estimating equations. RESULTS:
      Diagnostic-quality images were obtained for 150 zones. Periprosthetic signal
      intensity was greater than that of bone marrow in the distal femur on the fast
      STIR images, and no contrast enhancement was seen on the T1-weighted images (type
      I signal intensity pattern) in 11 zones. Signal intensity was greater than that
      of bone marrow on the fast STIR images, and contrast enhancement was seen on the
      T1-weighted images (type II signal intensity pattern) in 45 zones. Signal
      intensity was less than or equal to that of bone marrow on the fast STIR images,
      and no contrast enhancement was seen on the T1-weighted images (type III signal
      intensity pattern) in 94 zones. Type I and II patterns were associated with focal
      or nonfocal lucency, an unstable stem, and fibrosis or granuloma. A type III
      pattern was associated with a normal radiographic appearance, a stable stem, and
      normal bone tissue. Significant association was demonstrated between
      periprosthetic signal intensity and radiographic (P <.001, chi2 test and
      generalized estimating equations), surgical (P <.05, Mantel-Haenszel chi2 test
      and generalized estimating equations), and pathologic findings (P <.05, chi2
      test). CONCLUSION: Low-field-strength MR imaging depicted periprosthetic tissue
      signal intensity that was significantly associated with radiographic, surgical,
      and pathologic findings.

PMID- 14657309
TI  - Case 65: hemangioma of the chest wall.

PMID- 14657310
TI  - Air trapping in heart-lung transplant recipients: variability of anatomic
      distribution and extent at sequential expiratory thin-section CT.
AB  - PURPOSE: To evaluate the intrapatient reproducibility of the extent and anatomic
      distribution of air trapping at sequential expiratory thin-section computed
      tomographic (CT) examinations in heart-lung transplant recipients. MATERIALS AND
      METHODS: Nineteen heart-lung transplant recipients (eight with and 11 without
      bronchiolitis obliterans syndrome [BOS]) underwent three expiratory CT
      examinations within 1 hour. Residual volumes were measured at CT. Anatomic
      distribution and extent of air trapping were scored by two observers at two
      independent readings, and the reproducibility of observations was calculated for
      each feature. CT examination results were compared by using an analysis of
      variance that took into account interobserver and BOS and non-BOS effects. The
      Spearman rank correlation coefficient was calculated to test the association
      between variability of residual volumes and variability of the extent of air
      trapping. RESULTS: Residual volumes did not significantly differ between the
      three CT examinations (P =.556). Reproducibility values for findings of anatomic
      distribution of air trapping ranged from 84% to 95%, with a tendency toward
      improved reproducibility in patients without BOS. Mean reproducibility values for
      the extent of air trapping ranged from 97.1% to 97.7%, and no substantial
      difference in these values between patients with and those without BOS was
      observed. The Spearman rank coefficient for the correlation between variability
      of residual volumes and variability of extent of air trapping ranged from 0.382
      to 0.568 (P =.105-.016). No interobserver effect was detected (P =.944).
      CONCLUSION: Anatomic distribution and extent are reproducible characteristics of
      air trapping. No substantial variability of air trapping occurs in functionally
      stable heart-lung transplant recipients.

PMID- 14657311
TI  - Heart failure: evaluation of cardiopulmonary transit times with time-resolved MR
      angiography.
AB  - PURPOSE: To measure cardiopulmonary transit times in patients with heart failure
      by using low-dose, time-resolved magnetic resonance (MR) angiography and to
      determine if transit curves reflect conventional MR indexes of cardiac function.
      MATERIALS AND METHODS: Twenty-six patients with heart failure and left
      ventricular (LV) systolic dysfunction (17 men and nine women; age range, 22-78
      years) and thirteen control subjects (eight men and five women; age range, 23-59
      years) were examined with MR imaging. The examination consisted of rapid cine MR
      imaging throughout the heart, followed by contrast material-enhanced time
      resolved three-dimensional MR angiography of the cardiac chambers and pulmonary
      vasculature. Time-intensity curves for the pulmonary artery and ascending aorta
      were derived from the MR angiography images. Cardiopulmonary transit times and
      dispersions (full widths at half maximum [FWHM]) were determined from the curves.
      Transit times and FWHM values for the patients with heart failure were compared
      with control values by using two-tailed t tests, and transit time was correlated
      with standard LV functional parameters calculated from the cine MR images.
      RESULTS: Cardiopulmonary transit times and FWHM values were significantly
      prolonged in the patients with heart failure compared with those in the control
      patients (P <.001). Transit time correlated directly with LV end-diastolic and
      end-systolic volumes and inversely with LV ejection fraction (R > 0.60). However,
      transit time did not correlate strongly with age, body surface area, heart rate,
      LV mass, stroke volume, cardiac output, or sphericity index. CONCLUSION: Time
      resolved MR angiography allows determination of cardiopulmonary transit times
      that are significantly prolonged in heart failure and correlate directly with LV
      volumes and inversely with LV ejection fraction.

PMID- 14657312
TI  - Evaluation of patients after coronary artery bypass surgery: CT angiographic
      assessment of grafts and coronary arteries.
AB  - PURPOSE: To evaluate the accuracy of electrocardiography (ECG)-gated multi
      detector row computed tomography (CT) in enabling the detection of obstruction of
      both bypass grafts and coronary arteries in symptomatic patients who have
      undergone coronary artery bypass grafting. MATERIALS AND METHODS: ECG-gated
      contrast material-enhanced multi-detector row CT angiography was performed in 24
      patients after bypass surgery. Two independent blinded observers evaluated all
      graft and coronary segments (> or =2.0-mm diameter) for occlusion and stenosis
      (50%-99% luminal reduction). Conventional angiography was regarded as the
      standard of reference. Descriptive parameters were calculated, and the results
      for arterial grafts, venous grafts, and coronary arteries, as well as for high
      and low heart rates, were compared by using a two-sided Fisher exact test.
      RESULTS: The following results were obtained by observers 1 and 2, respectively:
      Of the 60 venous graft segments, 60 (100%) and 57 (95.0%) were assessable, with
      an overall detection of all 17 occlusions (both observers) and three (50.0%) and
      five (83.3%) of six stenoses. Of 26 arterial graft segments, 19 (73.1%) and 15
      (57.7%) were assessable. In the assessable segments, four of four (100%) and two
      of three (66.7%) stenoses and occlusions were detected, while one and two
      obstructions were located in nonassessable segments. Of 211 coronary segments,
      146 (69.2%) and 140 (66.4%) were assessable, and detection of 50%-100%
      obstruction yielded a sensitivity of 89.9% (71 of 79) and 79.4% (54 of 68) and a
      specificity of 74.6% (50 of 67) and 72.2% (52 of 72) for each observer. Unlike
      the assessment of venous and arterial grafts, assessment of the coronary arteries
      with multi-detector row CT was significantly better in patients with low heart
      rates (P <.01). CONCLUSION: Multi-detector row CT allows noninvasive angiographic
      evaluation of both coronary arteries and bypass grafts in patients who have
      undergone bypass surgery. Multi-detector row CT is more effective in examining
      venous grafts compared with arterial grafts and diffusely diseased coronary
      arteries.

PMID- 14657313
TI  - Diagnosis of acute pulmonary embolism in outpatients: comparison of thin
      collimation multi-detector row spiral CT and planar ventilation-perfusion
      scintigraphy.
AB  - PURPOSE: To compare multi-detector row computed tomography (CT) and ventilation
      perfusion (V-P) scintigraphy in the diagnosis of acute pulmonary embolism (PE) in
      outpatients who were cared for in the emergency department. MATERIALS AND
      METHODS: Ninety-four nonconsecutive patients, in whom acute PE was suspected,
      underwent thin-collimation multi-detector row CT (collimation, 4 x 1 mm; pitch,
      1.25; scanning time, 0.5 second) and V-P scintigraphy. Concordance between CT and
      scintigraphic images was used in the diagnosis of PE. Pulmonary angiography was
      performed within 24 hours if interpretations of V-P and spiral CT images were
      inconclusive or discordant. Sensitivity and specificity values were calculated
      for V-P scintigrams and CT scans of the lungs. The rates of conclusive results
      for scintigraphy and CT were compared. RESULTS: The sensitivity of thin
      collimation multi-detector row CT and V-P scintigraphy for the detection of PE
      was 96% (27 of 28; CI: 82%, 99%) and 98% (65 of 66; CI: 92%, 99%), respectively.
      The specificity of CT and V-P scintigraphy was 86% (24 of 28; CI: 67%, 96%) and
      88% (58 of 66; CI: 77%, 94%), respectively. Seven V-P scintigrams were of
      intermediate probability, and one spiral CT study was indeterminate. Examinations
      with spiral CT yielded conclusive results more often than examinations with
      planar V-P scintigraphy (P <.05). Five V-P scintigrams and spiral CT scans were
      discordant. Twelve pulmonary angiographic examinations were performed.
      Angiographic findings were concordant in 10 (91%) of 11 patients with conclusive
      CT scans in whom pulmonary angiography was attempted. CT was used to establish an
      alternative diagnosis in 19 (29%) of 66 patients in whom PE was excluded.
      CONCLUSION: Thin-collimation multi-detector row CT is more accurate than V-P
      scintigraphy in the diagnosis of acute PE in outpatients. Furthermore, CT
      provides alternative diagnoses for patients without PE on high-quality transverse
      or near-isotropic reformatted images.

PMID- 14657314
TI  - Screening US for blunt abdominal trauma: objective predictors of false-negative
      findings and missed injuries.
AB  - PURPOSE: To determine the risk for missed injury in patients with blunt abdominal
      trauma and negative findings at screening ultrasonography (US) and with
      coexistent hematuria or fracture of the sixth through 12th ribs, lumbar spine, or
      pelvis. MATERIALS AND METHODS: From a database of 4,000 patients screened with US
      for blunt abdominal trauma at a level 1 trauma center, the 3,679 patients with
      negative US findings were retrospectively classified by consensus of two authors
      into high-risk (n = 494) and low-risk (n = 3,185) groups based on the presence of
      hypothetical predictors of missed injury: hematuria (n = 96) or fracture of the
      sixth through 12th ribs (n = 216), lumbar spine (n = 105), or pelvis (n = 174).
      Outcome in each patient was determined by the same two authors consensually after
      retrospective review of the trauma registry and all radiologic, surgical, and
      autopsy reports. The risk for missed abdominal injury was determined for each
      patient risk group and for each hypothetical predictor. Risks were statistically
      compared by using the Pearson chi2, Fisher exact, or Fisher-Freeman-Halton exact
      test, depending on expected frequencies. RESULTS: High-risk patients were 24
      times more likely to have abdominal injuries after negative US findings (30
      [6.1%] of 494) than were low-risk patients (eight [0.25%] of 3,185) (P <.001).
      Among high-risk patients, the absolute risks for missed abdominal injury
      associated with specific predictors were 15.6% (15 of 96 patients) for hematuria,
      6.0% (13 of 216) for lower rib fractures, 7.6% (eight of 105) for lumbar spine
      fractures, and 5.2% (nine of 174) for pelvic fractures. Each of these risks was
      significantly higher for patients in the high-risk group than for those in the
      low-risk group (P <.001). CONCLUSION: Hematuria and fracture of the lower ribs,
      lumbar spine, or pelvis are objective predictors of missed abdominal injury in
      patients with blunt abdominal trauma and negative US findings, and such patients
      may benefit from additional screening with computed tomography.

PMID- 14657315
TI  - Detection of colorectal lesions: lower-dose multi-detector row helical CT
      colonography compared with conventional colonoscopy.
AB  - PURPOSE: To compare the performance of lower-dose multi-detector row helical
      computed tomographic (CT) colonography with that of conventional colonoscopy in
      the detection of colorectal lesions. MATERIALS AND METHODS: One hundred fifty
      eight patients underwent multi-detector row helical CT colonography (beam
      collimation, 4 x 2.5 mm; table feed, 17.5 mm/sec; voltage, 140 kV; and effective
      dose, 10 mAs) followed by conventional colonoscopy. Conventional colonoscopy
      served as the reference standard. Two radiologists interpreted CT colonographic
      images to assess the presence of polyps or carcinomas. Sensitivity was calculated
      on both a per-polyp and a per-patient basis. In the latter, specificity and
      positive and negative predictive values were also calculated. Weighted CT dose
      index was calculated on the basis of measurements obtained in a standard body
      phantom. Effective dose was estimated by using commercially available software.
      RESULTS: CT colonography correctly depicted all 22 carcinomas (sensitivity, 100%)
      and 52 of 74 polyps (sensitivity, 70.3%). Sensitivity for detection was 100% in
      all 13 polyps 10 mm or larger in diameter, 83.3% in 20 of 24 polyps 6-9 mm, and
      51.3% in 19 of 37 lesions 5 mm or smaller. With regard to the per-patient
      analysis, CT colonography had a sensitivity of 96.0%, a specificity of 96.6%, a
      positive predictive value of 94.1%, and a negative predictive value of 97.7%. The
      total weighted CT dose index for combined prone and supine acquisitions was 2.74
      mGy. The simulated effective doses for complete CT colonography were 1.8 mSv in
      men and 2.4 mSv in women. CONCLUSION: Lower-dose multi-detector row helical CT
      colonography ensures substantial dose reduction while maintaining excellent
      sensitivity for detection of colorectal carcinomas and polyps larger than 6 mm in
      diameter.

PMID- 14657316
TI  - Cardiovascular effects at multi-detector row CT colonography compared with those
      at conventional endoscopy of the colon.
AB  - PURPOSE: To compare the cardiovascular effects of computed tomographic (CT)
      colonography and conventional endoscopy in a group of patients undergoing both
      procedures. MATERIALS AND METHODS: A total of 144 patients underwent CT
      colonography followed by flexible sigmoidoscopy (40 patients) or colonoscopy (104
      patients). Pulse, blood pressure, and oxygen saturation were measured before,
      during, and after the procedures. Forty patients also underwent continuous Holter
      electrocardiographic (ECG) monitoring. Periprocedural pain was assessed by using
      a handheld counting device. Outcome variables were assessed by using a
      combination of paired t testing and multilevel linear regression. RESULTS: When a
      spasmolytic was not used, CT colonography was associated with only a small
      increase in oxygen saturation (P =.03), while use of a spasmolytic caused an
      increase in pulse (mean increase, 19.9 beats per minute; P <.001) and diastolic
      blood pressure (mean increase, 5 mm Hg; P <.001). Compared with that at CT,
      oxygen saturation decreased significantly during and after colonoscopy and
      sigmoidoscopy (mean decrease after colonoscopy with sedation, 1.0%; P <.001).
      Systolic and diastolic blood pressure also decreased during and after colonoscopy
      (mean systolic decrease after colonoscopy with sedation, 16.6 mm Hg, P <.001;
      mean diastolic decrease after colonoscopy with sedation, 7.5 mm Hg, P <.001).
      Patients were 30.3 times more likely to develop bradycardia after endoscopy (95%
      CI: 2.65, 346; P =.006). Ventricular couplets were significantly higher at
      endoscopy than at CT in patients with a history of cardiac disease (odds ratio:
      72.5 and 95% CI: 4.56, 1,153 at CT vs odds ratio: 14.6 and 95% CI: 0.96, 222 at
      endoscopy; P =.002). Patients were 1.89 times more likely to register pain during
      colonoscopy than during CT (95% CI: 1.06, 3.38; P =.03). CONCLUSION: CT
      colonography had no significant cardiovascular effect other than spasmolytic
      induced tachycardia. Endoscopy-and colonoscopy in particular-causes
      cardiovascular effects that are largely related to sedation. CT colonography is
      less painful than colonoscopy and is comparable to flexible sigmoidoscopy.

PMID- 14657317
TI  - Unresectable pulmonary malignancies: CT-guided percutaneous radiofrequency
      ablation--preliminary results.
AB  - PURPOSE: To assess whether percutaneous radiofrequency (RF) ablation of
      unresectable pulmonary malignancies is safe and technically feasible and to
      evaluate the usefulness of computed tomographic (CT) nodule densitometry as a
      tool for following up tumors after ablation. MATERIALS AND METHODS: Twelve
      patients (seven men and five women; mean age, 60.6 years) with unresectable
      disease (because of poor lung reserve or multifocality) underwent nodule CT
      densitometry and CT-guided percutaneous RF ablation of 19 lung tumors (six [32%]
      tumors were adenocarcinoma, one (5%) was large cell carcinoma, two (10%) were
      bronchoalveolar carcinoma, four (21%) were colorectal carcinoma, and six (32%)
      were sarcoma less than 50 cm2 in area (range, 0.25-35.00 cm2). No patients had
      symptoms of their disease before RF ablation. Follow-up CT densitometry was
      scheduled for 1, 3, 6, and 12 months after RF ablation. Lesions were evaluated
      for change in area and contrast enhancement at follow-up CT. RESULTS: RF ablation
      was well tolerated by all patients. Intraprocedural complications included 12
      cases of pneumothoraces (two patients required chest tube placement, while 10
      were asymptomatic and required no further treatment), two cases of pleural
      effusion, and two cases of moderate pain (one case during and one case both
      during and after the procedure). Mean follow-up was 4(1/2) months (range, 1-12
      months). In the eight patients with 3-month follow-up, lesion size increased in
      two and remained stable in six. Mean contrast enhancement, however, decreased
      from 46.8 HU (range, 19-107 HU) at baseline to 9.6 HU (range, 0-32 HU) at 1-2
      month follow-up. In the one patient with 12-month CT densitometry follow-up,
      lesion enhancement was less than 50% of that at baseline, and lesion diameter
      remained stable. CONCLUSION: These preliminary results show that percutaneous RF
      ablation is a safe and technically feasible management option for unresectable
      pulmonary malignancies. CT densitometry may have potential for future use as a
      noninvasive method of following up tumors after RF ablation.

PMID- 14657318
TI  - Characterization of biophysical and metabolic properties of cells labeled with
      superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR
      imaging.
AB  - PURPOSE: To evaluate the effect of using the ferumoxides-poly-l-lysine (PLL)
      complex for magnetic cell labeling on the long-term viability, function,
      metabolism, and iron utilization of mammalian cells. MATERIALS AND METHODS: PLL
      was incubated with ferumoxides for 60 minutes, incompletely coating the
      superparamagnetic iron oxide (SPIO) through electrostatic interactions. Cells
      were coincubated overnight with the ferumoxides-PLL complex, and iron uptake,
      cell viability, apoptosis indexes, and reactive oxygen species formation were
      evaluated. The disappearance or the life span of the detectable iron
      nanoparticles in cells was also evaluated. The iron concentrations in the media
      also were assessed at different time points. Data were expressed as the mean +/-
      1 SD, and one-way analysis of variance and the unpaired Student t test were used
      to test for significant differences. RESULTS: Intracytoplasmic nanoparticles were
      stained with Prussian blue when the ferumoxides-PLL complex had magnetically
      labeled the human mesenchymal stem and HeLa cells. The long-term viability,
      growth rate, and apoptotic indexes of the labeled cells were unaffected by the
      endosomal incorporation of SPIO, as compared with these characteristics of the
      nonlabeled cells. In nondividing human mesenchymal stem cells, endosomal iron
      nanoparticles could be detected after 7 weeks; however, in rapidly dividing
      cells, intracellular iron had disappeared by five to eight divisions. A
      nonsignificant transient increase in reactive oxygen species production was seen
      in the human mesenchymal stem and HeLa cell lines. Labeled human mesenchymal stem
      cells did not differentiate to other lineage. A significant increase in iron
      concentration was observed in both the human mesenchymal stem and HeLa cell media
      at day 7. CONCLUSION: Magnetic cellular labeling with the ferumoxides-PLL complex
      had no short- or long-term toxic effects on tumor or stem cells.

PMID- 14657319
TI  - Inhibition of neointimal proliferation with 188Re-labeled self-expanding nitinol
      stent in a sheep model.
AB  - PURPOSE: To evaluate a self-expanding rhenium 188 (188Re) radiochemically labeled
      radioactive stent in sheep. MATERIALS AND METHODS: A self-expanding nitinol stent
      (30 mm in length, 8 mm in diameter) coated with a functionalized polymer layer
      was radiolabeled with 188Re. Fifty prostheses, 25 of which were radioactive (mean
      radioactivity, 20 MBq +/- 3.8 [SD]) and 25 of which were nonradioactive, were
      implanted into the external iliac arteries of 25 sheep. Stent patency was
      assessed with angiography. Neointimal formation was assessed with intravascular
      ultrasonography and histologic examination 1 month (in all sheep) and 3 months
      (in 12 sheep) after implantation. The results were analyzed by using repeated
      measures analysis of variance with two repeated factors and paired t tests for
      comparison at each measuring point. RESULTS: All stents were placed successfully.
      Data in one animal had to be excluded from the study. After 3 months, a mean
      neointimal area reduction of 70 mm2 +/- 55 (SD) was observed inside the
      radioactive stents, and a mean lumen reduction of 126 mm2 +/- 39 was observed
      inside the nonradioactive control stents (P =.022). An edge effect was observed
      in the radioactive stents in that they showed an amount of neointimal formation
      at the edges that was similar to that seen in control stents. This neointimal
      formation accounted for the maximum lumen loss in the vascular segment with the
      stent. CONCLUSION: As compared with a nonradioactive stent, a beta particle
      emitting stent, through endovascular irradiation, significantly inhibits
      neointimal formation inside the stent but not at the stent edges.

PMID- 14657320
TI  - Radiation dose is reduced with a single-pass whole-body multi-detector row CT
      trauma protocol compared with a conventional segmented method: initial
      experience.
AB  - Radiation dose data were collected from a calibrated multi-detector row computed
      tomographic (CT) scanner during trauma CT. One protocol (used with 10 case
      subjects) involved a single-pass continuous whole-body acquisition from cranial
      vertex to symphysis pubis, while the other, conventional protocol (used with 10
      control subjects) involved scouting and scanning body segments (head, cervical
      spine, chest, abdomen, and pelvis) individually. Technical factors were kept
      constant within each body segment for the single-pass and the segmented
      protocols. Statistics included univariate analysis, two-tailed t testing to
      evaluate statistical significance of the summary statistic, and power and subject
      population contingency tables. The mean dose length product (DLP) with the single
      pass protocol was 17% lower than the sum of the DLPs of each of the individual
      body segment scans (P <.001). Analysis of power and subject population by using a
      difference in mean of 500 mGy. cm and an alpha of.05 revealed a (1-beta) of
      higher than 0.90 for a sample of 10 patients. Thus, a whole-body single-pass
      trauma protocol, compared with a typical segmented acquisition protocol matched
      for imaging technique, resulted in reduced total radiation dose. The reduction in
      radiation dose is thought to represent a reduction in redundant imaging at
      overlap zones between body segments scanned in the segmental protocol but not in
      the continuous acquisition.

PMID- 14657321
TI  - Intermittent-mode CT fluoroscopy-guided biopsy of the lung or upper abdomen with
      breath-hold monitoring and feedback: system development and feasibility.
AB  - A bellows-based breath-hold monitoring and feedback system was developed and
      evaluated for use in intermittent-mode computed tomographic (CT) fluoroscopy
      guided biopsy procedures in the lung or upper abdomen. The bellows system is
      described, and its feasibility is demonstrated in studies with a respiratory
      phantom and human volunteers. Results are reported for seven patients who
      underwent bellows-assisted biopsy. Breath-hold monitoring and feedback with the
      bellows system allow the patient to perform reliable breath holding at a
      preselected level. This optimizes intermittent-mode CT fluoroscopy-guided
      biopsies by allowing consistent visualization of the target lesion throughout the
      procedure.

PMID- 14657322
TI  - Time-of-flight MR angiography: comparison of 3.0-T imaging and 1.5-T imaging-
      initial experience.
AB  - Intracranial three-dimensional time-of-flight (TOF) magnetic resonance (MR)
      angiography was performed in seven healthy volunteers and eight patients with
      both 1.5-T and 3.0-T MR systems with standard and high spatial resolutions (true
      voxel sizes, 0.48 x 0.75 x 2.00 mm and 0.30 x 0.44 x 1.00 mm, respectively).
      Superior image quality and significantly better depiction of small vessel
      segments and vascular disease were observed at high-spatial-resolution 3.0-T TOF
      MR angiography but not at standard 1.5-T or standard 3.0-T TOF MR angiography (P
      <.01, respectively). Intracranial high-spatial-resolution TOF MR angiography at
      3.0-T imaging provides diagnostic improvement in studies of cerebrovascular
      disease.

PMID- 14657323
TI  - Excised bone structures in mice: imaging at three-dimensional synchrotron
      radiation micro CT.
AB  - Bone microarchitecture and mineralization were determined at three-dimensional
      synchrotron radiation micro computed tomography in two inbred mice strains.
      Distal metaphysis of the left femur was imaged in three dimensions at 6.65
      microm, whereas the right femur was analyzed with histomorphometry. Three
      dimensional quantitative parameters of trabecular and cortical bone architecture
      were computed. C3H/HeJ@Ico mice had greater bone density and thicker trabeculae;
      greater cortical bone density, cortical thickness, and porosity; and greater
      mineralization than did C57BL/6J@Ico mice. The technique is well suited for
      assessment of trabecular and cortical bone in small animals and at the same time
      provides mineralization status in three dimensions.

PMID- 14657324
TI  - Screening for lung cancer: is informed consent sufficient?

PMID- 14657325
TI  - Hypothesis testing of means.

PMID- 14657326
TI  - Double arterial phase multi-detector row helical CT for detection of
      hypervascular hepatocellular carcinoma.

PMID- 14657327
TI  - Pulmonary artery enhancement at CT pulmonary angiography.

PMID- 14657328
TI  - The art of teaching radiology.

PMID- 14657330
TI  - Measurements of the concentration and composition of nuclei for cirrus formation.
AB  - This article addresses the need for new data on indirect effects of natural and
      anthropogenic aerosol particles on atmospheric ice clouds. Simultaneous
      measurements of the concentration and composition of tropospheric aerosol
      particles capable of initiating ice in cold (cirrus) clouds are reported.
      Measurements support that cirrus formation occurs both by heterogeneous
      nucleation by insoluble particles and homogeneous (spontaneous) freezing of
      particles containing solutions. Heterogeneous ice nuclei concentrations in the
      cirrus regime depend on temperature, relative humidity, and the concentrations
      and physical and chemical properties of aerosol particles. The cirrus-active
      concentrations of heterogeneous nuclei measured in November over the western U.S.
      were <0.03 cm-3. Considering previous modeling studies, this result suggests a
      predominant potential impact of these nuclei on cirrus formed by slow, large
      scale lifting or small cooling rates, including subvisual cirrus. The most common
      heterogeneous ice nuclei were identified as relatively pure mineral dusts and
      metallic particles, some of which may have origin through anthropogenic
      processes. Homogeneous freezing of large numbers of particles was detected above
      a critical relative humidity along with a simultaneous transition in nuclei
      composition toward that of the sulfate-dominated total aerosol population. The
      temperature and humidity conditions of the homogeneous nucleation transition were
      reasonably consistent with expectations based on previous theoretical and
      laboratory studies but were highly variable. The strong presence of certain
      organic pollutants was particularly noted to be associated with impedance of
      homogeneous freezing.

PMID- 14657329
TI  - Light- and pH-dependent structural changes in the PsbS subunit of photosystem II.
AB  - In higher plants, the PsbS subunit of photosystem II (PSII) plays a crucial role
      in pH- and xanthophyll-dependent nonphotochemical quenching of excess absorbed
      light energy, thus contributing to the defense mechanism against photoinhibition.
      We determined the amino acid sequence of Zea mays PsbS and produced an antibody
      that recognizes with high specificity a region of the protein located in the
      stroma-exposed loop between the second and third putative helices. By means of
      this antiserum, the thylakoid membranes of various higher plant species revealed
      the presence of a 42-kDa protein band, indicating the formation of a dimer of the
      21-kDa PsbS protein. Crosslinking experiments and immunoblotting with other
      antisera seem to exclude the formation of a heterodimer with other PSII protein
      components. The PsbS monomer/dimer ratio in isolated thylakoid membranes was
      found to vary with luminal pH in a reversible manner, the monomer being the
      prevalent form at acidic and the dimer at alkaline pH. In intact chloroplasts and
      whole plants, dimer-to-monomer conversion is reversibly induced by light, known
      to cause luminal acidification. Sucrose-gradient centrifugation revealed a
      prevalent association of the PsbS monomer and dimer with light-harvesting complex
      and PSII core complexes, respectively. The finding of the existence of a light
      induced change in the quaternary structure of the PsbS subunit may contribute to
      understanding the mechanism of PsbS action during nonphotochemical quenching.

PMID- 14657331
TI  - Detection of cancer-specific markers amid massive mass spectral data.
AB  - We propose a comprehensive pattern recognition procedure that will achieve best
      discrimination between two or more sets of subjects with data in the same
      coordinate system. Applying the procedure to MS data of proteomic analysis of
      serum from ovarian cancer patients and serum from cancer-free individuals in the
      Food and Drug Administration/National Cancer Institute Clinical Proteomics
      Database, we have achieved perfect discrimination (100% sensitivity, 100%
      specificity) of patients with ovarian cancer, including early-stage disease, from
      normal controls for two independent sets of data. Our procedure identifies the
      best subset of proteomic biomarkers for optimal discrimination between the groups
      and appears to have higher discriminatory power than other methods reported to
      date. For large-scale screening for diseases of relatively low prevalence such as
      ovarian cancer, almost perfect specificity and sensitivity of the detection
      system is critical to avoid unmanageably high numbers of false-positive cases.

PMID- 14657332
TI  - Vacuolar sorting receptor for seed storage proteins in Arabidopsis thaliana.
AB  - The seeds of higher plants accumulate large quantities of storage protein. During
      seed maturation, storage protein precursors synthesized on rough endoplasmic
      reticulum are sorted to protein storage vacuoles, where they are converted into
      the mature forms and accumulated. Previous attempts to determine the sorting
      machinery for storage proteins have not been successful. Here we show that a type
      I membrane protein, AtVSR1/AtELP, of Arabidopsis functions as a sorting receptor
      for storage proteins. The atvsr1 mutant missorts storage proteins by secreting
      them from cells, resulting in an enlarged and electron-dense extracellular space
      in the seeds. The atvsr1 seeds have distorted cells and smaller protein storage
      vacuoles than do WT seeds, and atvsr1 seeds abnormally accumulate the precursors
      of two major storage proteins, 12S globulin and 2S albumin, together with the
      mature forms of these proteins. AtVSR1 was found to bind to the C-terminal
      peptide of 12S globulin in a Ca2+-dependent manner. These findings demonstrate a
      receptor-mediated transport of seed storage proteins to protein storage vacuoles
      in higher plants.

PMID- 14657333
TI  - Notch signaling controls multiple steps of pancreatic differentiation.
AB  - Multiple cell types of the pancreas appear asynchronously during embryogenesis,
      which requires that pancreatic progenitor cell potential changes over time. Loss
      of-function studies have shown that Notch signaling modulates the differentiation
      of these progenitors, but it remains unclear how and when the Notch pathway acts.
      We established a modular transgenic system to heritably activate mouse Notch1 in
      multiple types of progenitors and differentiated cells. We find that
      misexpression of activated Notch in Pdx1-expressing progenitor cells prevents
      differentiation of both exocrine and endocrine lineages. Progenitors remain
      trapped in an undifferentiated state even if Notch activation occurs long after
      the pancreas has been specified. Furthermore, endocrine differentiation is
      associated with escape from this activity, because Ngn3-expressing endocrine
      precursors are susceptible to Notch inhibition, whereas fully differentiated
      endocrine cells are resistant.

PMID- 14657334
TI  - The atherogenic effect of excess methionine intake.
AB  - Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in
      the methylation and transsulfuration pathways. Elevated plasma homocysteine
      (hyperhomocysteinemia) is associated with occlusive vascular disease. Whether
      homocysteine per se or a coincident metabolic abnormality causes vascular disease
      is still an open question. Animals with genetic hyperhomocysteinemia have so far
      not displayed atheromatous lesions. However, when methionine-rich diets are used
      to induce hyperhomocysteinemia, vascular pathology is often observed. Such
      studies have not distinguished the effects of excess dietary methionine from
      those of hyperhomocysteinemia. We fed apolipoprotein E-deficient mice with
      experimental diets designed to achieve three conditions: (i) high methionine
      intake with normal blood homocysteine; (ii) high methionine intake with B vitamin
      deficiency and hyperhomocysteinemia; and (iii) normal methionine intake with B
      vitamin deficiency and hyperhomocysteinemia. Mice fed methionine-rich diets had
      significant atheromatous pathology in the aortic arch even with normal plasma
      homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe
      hyperhomocysteinemia without any increase in vascular pathology. Our findings
      suggest that moderate increases in methionine intake are atherogenic in
      susceptible mice. Although homocysteine may contribute to the effect of
      methionine, high plasma homocysteine was not independently atherogenic in this
      model. Some product of excess methionine metabolism rather than high plasma
      homocysteine per se may underlie the association of homocysteine with vascular
      disease.

PMID- 14657335
TI  - Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect
      that is modulated by IL-7-mediated signaling.
AB  - A balance between survival and apoptotic signals regulates B cell development.
      These signals are tightly regulated by a host of molecules, including IL-7.
      Abnormal signaling events may lead to neoplastic transformation of progenitor B
      cells. Signal transduction inhibitors potentially may modulate these abnormal
      signals. Inhibitors of the mammalian target of rapamycin (mTOR) such as rapamycin
      have been used as immunosuppressive agents. We hypothesized that rapamycin might
      demonstrate activity against B-precursor acute lymphoblastic leukemia. We have
      found that rapamycin inhibited growth of B-precursor acute lymphoblastic leukemia
      lines in vitro, with evidence of apoptotic cell death. This growth inhibition was
      reversible by IL-7. One candidate as a signaling intermediate cross-regulated by
      rapamycin and IL-7 was p70 S6 kinase. Rapamycin also demonstrated in vivo
      activity in E mu-ret transgenic mice, which develop pre-B leukemia/lymphoma: E mu
      ret transgenic mice with advanced disease treated daily with rapamycin as a
      single agent showed a >2-fold increase in length of survival as compared with
      symptomatic littermates who received vehicle alone. These results suggest that
      mammalian target of rapamycin inhibitors may be effective agents against leukemia
      and that one of the growth signals inhibited by this class of drugs in precursor
      B leukemic cells may be IL-7-mediated.

PMID- 14657336
TI  - Converting conformational changes to electrostatic energy in molecular motors:
      The energetics of ATP synthase.
AB  - F1-ATPase is the catalytic component of the ATP synthase molecular machine
      responsible for most of the uphill synthesis of ATP in living systems. The
      enormous advances in biochemical and structural studies of this machine provide
      an opportunity for detailed understanding of the nature of its rotary mechanism.
      However, further quantitative progress in this direction requires development of
      reliable ways of translating the observed structural changes to the corresponding
      energies. This requirement is particularly challenging because we are dealing
      with a large system that couples major structural changes with a chemical
      process. The present work provides such a structure-function correlation by using
      the linear response approximation to describe the rotary mechanism. This approach
      allows one to evaluate the energy of transitions between different conformational
      states by considering only the changes in the corresponding electrostatic
      energies of the ligands. The relevant energetics are also obtained by calculating
      the linear response approximation-based free energies of transferring the ligands
      from water to the different sites of F1-ATPase in their different conformational
      states. We also use the empirical valence bond approach to evaluate the actual
      free-energy profile for the ATP synthesis in the different conformational states
      of the system. Integrating the information from the different approaches provides
      a semiquantitative structure-function correlation for F1-ATPase. It is found that
      the conformational changes are converted to changes in the electrostatic
      interaction between the protein and its ligands, which drives the ATP synthesis.

PMID- 14657337
TI  - Beclin 1, an autophagy gene essential for early embryonic development, is a
      haploinsufficient tumor suppressor.
AB  - The biochemical properties of beclin 1 suggest a role in two fundamentally
      important cell biological pathways: autophagy and apoptosis. We show here that
      beclin 1-/- mutant mice die early in embryogenesis and beclin 1+/- mutant mice
      suffer from a high incidence of spontaneous tumors. These tumors continue to
      express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a
      haploinsufficient tumor suppressor gene. Beclin 1-/- embryonic stem cells have a
      severely altered autophagic response, whereas their apoptotic response to serum
      withdrawal or UV light is normal. These results demonstrate that beclin 1 is a
      critical component of mammalian autophagy and establish a role for autophagy in
      tumor suppression. They both provide a biological explanation for recent evidence
      implicating beclin 1 in human cancer and suggest that mutations in other genes
      operating in this pathway may contribute to tumor formation through deregulation
      of autophagy.

PMID- 14657338
TI  - Crystal structure of the complete core of archaeal signal recognition particle
      and implications for interdomain communication.
AB  - Targeting of secretory and membrane proteins by the signal recognition particle
      (SRP) is evolutionarily conserved, and the multidomain protein SRP54 acts as the
      key player in SRP-mediated protein transport. Binding of a signal peptide to
      SRP54 at the ribosome is coordinated with GTP binding and subsequent complex
      formation with the SRP receptor. Because these functions are localized to
      distinct domains of SRP54, communication between them is essential. We report the
      crystal structures of SRP54 from the Archaeon Sulfolobus solfataricus with and
      without its cognate SRP RNA binding site (helix 8) at 4-A resolution. The two
      structures show the flexibility of the SRP core and the position of SRP54
      relative to the RNA. A long linker helix connects the GTPase (G domain) with the
      signal peptide binding (M) domain, and a hydrophobic contact between the N and M
      domains relates the signal peptide binding site to the G domain. Hinge regions
      are identified in the linker between the G and M domains (292-LGMGD) and in the N
      terminal part of the M domain, which allow for structural rearrangements within
      SRP54 upon signal peptide binding at the ribosome.

PMID- 14657339
TI  - Myeloperoxidase up-regulates the catalytic activity of inducible nitric oxide
      synthase by preventing nitric oxide feedback inhibition.
AB  - Kinetic and structure analysis of inducible nitric oxide synthase (iNOS) revealed
      that, in addition to the increase of iNOS expression in inflamed areas, the major
      pathway causing overproduction of NO is destabilization of the iNOS-nitrosyl
      complex(es) that form during steady-state catalysis. Formation of such a complex
      allows iNOS to operate at only a fraction (20-30%) of its maximum activity. Thus,
      bioavailability of NO scavengers at sites of inflammation may play an essential
      role in up-regulation of the catalytic activity of iNOS, by preventing the
      catalytic activity inhibition that is attributed to nitrosyl complex formation.
      Myeloperoxidase (MPO), a major NO scavenger, is a pivotal enzyme involved in
      leukocyte-mediated host defenses. It is thought to play a pathogenic role under
      circumstances such as acute inflammatory tissue injury and chronic inflammatory
      conditions. However, a detailed understanding of the interrelationship between
      iNOS and MPO at sites of inflammation is lacking. We used direct spectroscopic,
      HPLC, and selective NO-electrode measurements to determine the interdependent
      relationship that exists between iNOS and MPO and the role of the MPO/H2O2 system
      in up-regulating the catalytic activity of iNOS that occurs at sites of
      inflammation. Scavenging free NO from the iNOS milieu by the MPO/H2O2 system
      subsequently restores the full capacity of iNOS to convert L-arginine to product
      (NO), as judged by the increase in the rates of citrulline and nitrite/nitrate
      production. Studies of iNOS catalytic mechanisms and function are essential to a
      more fundamental understanding of these factors, which govern iNOS-dependent
      processes in human health and disease.

PMID- 14657340
TI  - Catalysis and rotation of F1 motor: cleavage of ATP at the catalytic site occurs
      in 1 ms before 40 degree substep rotation.
AB  - F1, a water-soluble portion of FoF1-ATP synthase, is an ATP hydrolysis-driven
      rotary motor. The central gamma-subunit rotates in the alpha 3 beta 3 cylinder by
      repeating the following four stages of rotation: ATP-binding dwell, rapid 80
      degrees substep rotation, interim dwell, and rapid 40 degrees substep rotation.
      At least two 1-ms catalytic events occur in the interim dwell, but it is still
      unclear which steps in the ATPase cycle, except for ATP binding, correspond to
      these events. To discover which steps, we analyzed rotations of F1 subcomplex
      (alpha 3 beta 3 gamma) from thermophilic Bacillus PS3 under conditions where
      cleavage of ATP at the catalytic site is decelerated: hydrolysis of ATP by the
      catalytic-site mutant F1 and hydrolysis of a slowly hydrolyzable substrate ATP
      gamma S (adenosine 5'-[gamma-thio]triphosphate) by wild-type F1. In both cases,
      interim dwells were extended as expected from bulk phase kinetics, confirming
      that cleavage of ATP takes place during the interim dwell. Furthermore, the
      results of ATP gamma S hydrolysis by the mutant F1 ensure that cleavage of ATP
      most likely corresponds to one of the two 1-ms events and not some other faster
      undetected event. Thus, cleavage of ATP on F1 occurs in 1 ms during the interim
      dwell, and we call this interim dwell catalytic dwell.

PMID- 14657341
TI  - Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide
      family with orexigenic activity.
AB  - A neuropeptide was isolated from a frog brain extract by HPLC purification and
      characterized by mass spectrometry. This 26-aa neuropeptide, which belongs to the
      RFamide peptide family, was designated 26RFa, and its primary structure was
      established as VGTALGSLAEELNGYNRKKGGFSFRF-NH2. Research in databases revealed the
      presence of sequences homologous to frog 26RFa in the human genome and in rat
      ESTs. On the basis of this sequence information, the cDNAs encoding the human and
      rat 26RFa precursors were cloned. The two preproteins show a similar
      organization, with the 26RFa sequence located in the C-terminal region of the
      precursor. Human preprotein (prepro)-26RFa encodes an additional putative RFamide
      peptide that is not found in the rat precursor. The primary structures of human,
      rat, and frog 26RFa exhibit approximately 80% identity, and the C-terminal
      octapeptide has been fully conserved from amphibians to mammals. In situ
      hybridization histochemistry revealed that, in the rat brain, the 26RFa gene is
      exclusively expressed in the ventromedial hypothalamic nucleus and in the lateral
      hypothalamic area. 26RFa induced a dose-dependent stimulation in cAMP production
      by rat pituitary cells in vitro and markedly increased food intake in mice. The
      conservation of the primary structure of 26RFa during vertebrate evolution, the
      discrete localization of the mRNA encoding its precursor in hypothalamic nuclei
      involved in the control of feeding behavior, and the observation that 26RFa
      possesses orexigenic properties indicate that this neuropeptide may play
      important biological functions.

PMID- 14657342
TI  - Redox regulation of surface protein thiols: identification of integrin alpha-4 as
      a molecular target by using redox proteomics.
AB  - Thiols affect a variety of cell functions, an effect known as redox regulation.
      We show here that treatment (1-2 h) of cells with 0.1-5 mM N-acetyl-L-cysteine
      (NAC) increases surface protein thiol expression in human peripheral blood
      mononuclear cells. This effect is not associated with changes in cellular
      glutathione (GSH) and is also observed with a non-GSH precursor thiol N-acetyl-D
      cysteine or with GSH itself, which is not cell-permeable, suggesting a direct
      reducing action. NAC did not augment protein SH in the cytosol, indicating that
      they are already maximally reduced under normal, nonstressed, conditions. By
      using labeling with a non permeable, biotinylated SH reagent followed by two
      dimensional gel electrophoresis and analysis by MS, we identified some of the
      proteins associated with the membrane that are reduced by NAC. These proteins
      include the following: integrin alpha-4, myosin heavy chain (nonmuscle type A),
      myosin light-chain alkali (nonmuscle isoform), and beta-actin. NAC pretreatment
      augmented integrin alpha-4-dependent fibronectin adhesion and aggregation of
      Jurkat cells without changing its expression by fluorescence-activated cell
      sorter, suggesting that reduction of surface disulfides can affect proteins
      function. We postulate that some of the activities of NAC or other thiol
      antioxidants may not only be due to free radical scavenging or increase of
      intracellular GSH and subsequent effects on transcription factors, but could
      modify the redox state of functional membrane proteins with exofacial SH critical
      for their activity.

PMID- 14657343
TI  - Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion
      culture increases with increasing fluid shear forces.
AB  - In this study we report on direct involvement of fluid shear stresses on the
      osteoblastic differentiation of marrow stromal cells. Rat bone marrow stromal
      cells were seeded in 3D porous titanium fiber mesh scaffolds and cultured for 16
      days in a flow perfusion bioreactor with perfusing culture media of different
      viscosities while maintaining the fluid flow rate constant. This methodology
      allowed exposure of the cultured cells to increasing levels of mechanical
      stimulation, in the form of fluid shear stress, whereas chemotransport conditions
      for nutrient delivery and waste removal remained essentially constant. Under
      similar chemotransport for the cultured cells in the 3D porous scaffolds,
      increasing fluid shear forces led to increased mineral deposition, suggesting
      that the mechanical stimulation provided by fluid shear forces in 3D flow
      perfusion culture can indeed enhance the expression of the osteoblastic
      phenotype. Increased fluid shear forces also resulted in the generation of a
      better spatially distributed extracellular matrix inside the porosity of the 3D
      titanium fiber mesh scaffolds. The combined effect of fluid shear forces on the
      mineralized extracellular matrix production and distribution emphasizes the
      importance of mechanosensation on osteoblastic cell function in a 3D environment.

PMID- 14657344
TI  - The hyperpolarization-activated channel HCN4 is required for the generation of
      pacemaker action potentials in the embryonic heart.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated cation currents, termed If
      or Ih, are generated by four members of the hyperpolarization-activated, cyclic
      nucleotide-gated cation (HCN) channel family. These currents have been proposed
      to contribute to several functions including pacemaker activity in heart and
      brain, control of resting potential, and neuronal plasticity. Transcripts of the
      HCN4 isoform have been found in cardiomyocytes and neurons, but the physiological
      role of this channel is unknown. Here we show that HCN4 is essential for the
      proper function of the developing cardiac conduction system. In wild-type
      embryos, HCN4 is highly expressed in the cardiac region where the early
      sinoatrial node develops. Mice lacking HCN4 channels globally, as well as mice
      with a selective deletion of HCN4 in cardiomyocytes, died between embryonic days
      9.5 and 11.5. On average, If in cardiomyocytes from mutant embryos is reduced by
      85%. Hearts from HCN4-deficient embryos contracted significantly slower compared
      with wild type and could not be stimulated by cAMP. In both wild-type and HCN4-/-
      mice, cardiac cells with "primitive" pacemaker action potentials could be found.
      However, cardiac cells with "mature" pacemaker potentials, observed in wild-type
      embryos starting at day 9.0, were not detected in HCN4-deficient embryos. Thus,
      HCN4 channels are essential for the proper generation of pacemaker potentials in
      the emerging sinoatrial node.

PMID- 14657345
TI  - Amino acid substitutions in the thyroglobulin gene are associated with
      susceptibility to human and murine autoimmune thyroid disease.
AB  - The 8q24 locus, which contains the thyroglobulin (Tg) gene, was previously shown
      to be strongly linked with autoimmune thyroid disease (AITD). We sequenced all 48
      exons of the Tg gene and identified 14 single-nucleotide polymorphisms (SNPs).
      Case control association studies demonstrated that an exon 10-12 SNP cluster and
      an exon 33 SNP were significantly associated with AITD (P < 0.01). Haplotype
      analysis demonstrated that the combination of these two SNP groups was more
      significantly associated with AITD (P < 0.001). Gene-gene interaction studies
      provided evidence for an interaction between HLA-DR3 and the exon 33 SNP, giving
      an odds ratio of 6.1 for Graves' disease. We then sequenced exons 10,12, and 33
      of the mouse Tg gene in 19 strains of mice. Fifty percent of the strains
      susceptible to thyroiditis had a unique SNP haplotype at exons 10 and 12, whereas
      none of the mouse strains that were resistant to thyroiditis had this SNP
      haplotype (P = 0.01). We concluded that Tg is a susceptibility gene for AITD,
      both in humans in and in mice. A combination of at least two Tg SNPs conferred
      susceptibility to human AITD. Moreover, the exon 33 SNP showed evidence for
      interaction with HLA-DR3 in conferring susceptibility to Graves' disease.

PMID- 14657347
TI  - MED1: a central molecule for maintenance of genome integrity and response to DNA
      damage.

PMID- 14657346
TI  - Mitotic partitioning and selective reorganization of tissue-specific
      transcription factors in progeny cells.
AB  - Postmitotic gene expression requires restoration of nuclear organization and
      assembly of regulatory complexes. The hematopoietic and osteogenic Runx
      (Cbfa/AML) transcription factors are punctately organized in the interphase
      nucleus and provide a model for understanding the subnuclear organization of
      tissue-specific regulatory proteins after mitosis. Here we have used quantitative
      in situ immunofluorescence microscopy and quantitative image analysis to show
      that Runx factors undergo progressive changes in cellular localization during
      mitosis while retaining a punctate distribution. In comparison, the acetyl
      transferase p300 and acetylated histone H4 remain localized with DNA throughout
      mitosis while the RNA processing factor SC35 is excluded from mitotic chromatin.
      Subnuclear organization of Runx foci is completely restored in telophase, and
      Runx proteins are equally partitioned into progeny nuclei. In contrast,
      subnuclear organization of SC35 is restored subsequent to telophase. Our results
      show a sequential reorganization of Runx and its coregulatory proteins that
      precedes restoration of RNA processing speckles. Thus, mitotic partitioning and
      spatiotemporal reorganization of regulatory proteins together render progeny
      cells equivalently competent to support phenotypic gene expression.

PMID- 14657348
TI  - Biography of Robert A. Lamb.

PMID- 14657349
TI  - MSH2 and ATR form a signaling module and regulate two branches of the damage
      response to DNA methylation.
AB  - The mismatch repair proteins function upstream in the DNA damage signaling
      pathways induced by the DNA methylating agent N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG). We report that MSH2 (MutS homolog 2) protein interacts
      with the ATR (ATM- and Rad3-related) kinase to form a signaling module and
      regulate the phosphorylation of Chk1 and SMC1 (structure maintenance of
      chromosome 1). We found that phosphorylation of Chk1 by ATR also requires
      checkpoint proteins Rad17 and replication protein A. In contrast, phosphorylation
      of SMC1 by ATR is independent of Rad17 and replication protein A, suggesting that
      the signaling pathway leading to SMC1 phosphorylation is distinct from that
      mediated by the checkpoint proteins. In addition, both MSH2 and Rad17 are
      required for the activation of the S-phase checkpoint to suppress DNA synthesis
      in response to MNNG, and phosphorylation of SMC1 is required for cellular
      survival. These data support a model in which MSH2 and ATR function upstream to
      regulate two branches of the response pathway to DNA damage caused by MNNG.

PMID- 14657350
TI  - The molecular basis for the high photosensitivity of rhodopsin.
AB  - Based on structural information derived from the F NMR data of labeled
      rhodopsins, rhodopsin crystal structure, and excited-state properties of model
      polyenes, we propose a molecular mechanism that accounts specifically for the
      causes of the well-known enhanced photoreactivity of rhodopsin (increased rates
      and quantum yield of isomerization). It involves the key features of close
      proximity of C-187 to H-12 and chromophore bond lengthening upon light
      absorption. The resultant "sudden punch" to H-12 triggers dual processes of decay
      of the Franck-Condon-excited rhodopsin, a productive directed photoisomerization
      and a nonproductive decay returning to the ground state as two separate molecular
      pathways [based on real-time fluorescence results of Chosrowjan, H., Mataga, N.,
      Shibata, Y., Tachibanaki, S., Kandori, H., Shichida, Y., Okada, T. & Kouyama, T.
      (1998) J. Am. Chem. Soc. 120, 9706-9707]. The two processes are controlled by the
      local protein structure: an empty space provided by the intradiscal loop
      connecting transmembrane helices 4 and 5 and a protein wall composed of amino
      acid units in transmembrane 3. Suggestions, involving retinal analogs and
      rhodopsin mutants, to improve the unusually high photosensitivity of rhodopsin
      are proposed.

PMID- 14657351
TI  - Use of thiol-disulfide equilibria to measure the energetics of assembly of
      transmembrane helices in phospholipid bilayers.
AB  - Despite significant efforts and promising progress, the understanding of membrane
      protein folding lags behind that of soluble proteins. Insights into the
      energetics of membrane protein folding have been gained from biophysical studies
      in membrane-mimicking environments (primarily detergent micelles). However, the
      development of techniques for studying the thermodynamics of folding in
      phospholipid bilayers remains a considerable challenge. We had previously used
      thiol-disulfide exchange to study the thermodynamics of association of
      transmembrane alpha-helices in detergent micelles; here, we extend this
      methodology to phospholipid bilayers. The system for this study is the
      homotetrameric M2 proton channel protein from the influenza A virus.
      Transmembrane peptides from this protein specifically self-assemble into
      tetramers that retain the ability to bind to the drug amantadine. Thiol-disulfide
      exchange under equilibrium conditions was used to quantitatively measure the
      thermodynamics of this folding interaction in phospholipid bilayers. The effects
      of phospholipid acyl chain length and cholesterol on the peptide association were
      investigated. The association of the helices strongly depends on the thickness of
      the bilayer and cholesterol levels present in the phospholipid bilayer. The most
      favorable folding occurred when there was a good match between the width of the
      apolar region of the bilayer and the hydrophobic length of the transmembrane
      helix. Physiologically relevant variations in the cholesterol level are
      sufficient to strongly influence the association. Evaluation of the energetics of
      peptide association in the presence and absence of cholesterol showed a
      significantly tighter association upon inclusion of cholesterol in the lipid
      bilayers.

PMID- 14657352
TI  - CatSper1 required for evoked Ca2+ entry and control of flagellar function in
      sperm.
AB  - CatSper family proteins are putative ion channels expressed exclusively in
      membranes of the sperm flagellum and required for male fertility. Here, we show
      that mouse CatSper1 is essential for depolarization-evoked Ca2+ entry and for
      hyperactivated movement, a key flagellar function. CatSper1 is not needed for
      other developmental landmarks, including regional distributions of CaV1.2,
      CaV2.2, and CaV2.3 ion channel proteins, the cAMP-mediated activation of motility
      by HCO3-, and the protein phosphorylation cascade of sperm capacitation. We
      propose that CatSper1 functions as a voltage-gated Ca2+ channel that controls
      Ca2+ entry to mediate the hyperactivated motility needed late in the preparation
      of sperm for fertilization.

PMID- 14657353
TI  - IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1
      dependent and -independent mechanisms.
AB  - IL-27, a novel heterodimeric cytokine produced by antigen-presenting cells,
      signals through the T cell cytokine receptor (TCCR)/WSX-1 expressed on naive CD4+
      T cells and natural killer cells. TCCR/WSX-1 deficiency results in delayed T
      helper type 1 (TH1) development through an unresolved mechanism. We report here
      that IL-27 stimulation in developing murine T helper cells potently induces the
      expression of the major TH1-specific transcription factor T-bet and its
      downstream target IL-12R beta2, independently of IFN gamma. In addition, IL-27
      suppresses basal expression of GATA-3, the critical TH2-specific transcription
      factor that inhibits TH1 development by down-regulating signal transducer and
      activator of transcription (Stat) 4. IL-27 signaling through TCCR/WSX-1 induces
      phosphorylation of Stat1, Stat3, Stat4, and Stat5. Stat1 is required for
      suppression of GATA-3, but T-bet induction by IL-27 can also be mediated through
      a Stat1-independent pathway. Despite its TH1-like signaling profile, IL-27 is not
      sufficient to drive the differentiation of CD4+ T cells into IFN gamma-producing
      cells. Similarly, IL-27 induces T-bet expression in primary natural killer cells,
      but this does not result in an increase of IFN gamma production or cytotoxic
      activity. Therefore, although IL-27 is unable to drive IFN gamma production on
      its own, it plays an important role in the early steps of TH1 commitment by
      contributing in a paracrine manner to the control of IL-12 responsiveness.

PMID- 14657354
TI  - TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of
      Cdc25A with resultant cell-cycle arrest.
AB  - The ability of the transforming growth factor beta (TGF-beta) signaling pathways
      to inhibit proliferation of most cells while stimulating proliferation of others
      remains a conundrum. In this article, we report that the absence of RhoA and
      p160ROCK activity in fibroblastic NIH 3T3 cells and its presence in epithelial
      NMuMG cells can at least partially explain the difference in the TGF-beta growth
      response. Further, evidence is presented for TGF-beta-stimulated p160ROCK
      translocation to the nucleus and inhibitory phosphorylation of the cyclin
      dependent kinase-activating phosphatase, Cdc25A. The resultant suppression of
      Cdk2 activity contributes to G1/S inhibition in NMuMG cells. These data provide
      evidence that signaling through RhoA and p160ROCK is important in TGF-beta
      inhibition of cell proliferation and links signaling components for epithelial
      transdifferentiation with regulation of cell-cycle progression.

PMID- 14657355
TI  - Circadian gene expression in mammalian fibroblasts revealed by real-time
      luminescence reporting: temperature compensation and damping.
AB  - Mammalian cells such as rat-1 fibroblasts have been shown to exhibit daily
      oscillations in the expression of several gene transcripts in culture. After
      induction, these oscillations persist with a period of approximately 24 h for
      several days. This characteristic suggests that the oscillations are controlled
      by a circadian clock, but the crucial criterion of temperature compensation has
      not been demonstrated for rat-1 fibroblasts. We have developed an automated assay
      of circadian expression of the mPer1 promoter in rat-1 fibroblasts that have been
      stably transfected with a luciferase reporter. Using this cell culture-based in
      vitro luminescent reporter assay, we found that the daily oscillation of mPer1
      promoter activity in rat-1 cells is temperature compensated over the range of
      28.5-36.5 degrees C. This finding means that these oscillations are bona fide
      circadian rhythms. Moreover, the circadian clock of these homeothermic mammalian
      cells not only is temperature compensated but also is overcompensated such that
      it runs faster at cooler temperatures (Q10 of 0.85-0.88). The oscillations in rat
      1 fibroblasts damp more rapidly at cooler temperatures, and damping is not due to
      cells becoming unhealthy because a second stimulus will reinitiate a robust
      rhythm. These data show that rat-1 cell cultures that are stably transfected with
      luminescence reporters are an excellent model system for studying circadian
      clocks at the cellular level in mammals.

PMID- 14657356
TI  - Expression of conditional fear with and without awareness.
AB  - Conditional responding during simple Pavlovian conditioning is often
      characterized as a form of implicit memory. The extent to which this type of
      associative learning is independent of awareness is an issue of continuing
      debate. Previous studies have demonstrated conditioning in the absence of
      awareness. However, their results have been questioned based on methodological
      concerns with postexperimental questionnaires. In the present study, skin
      conductance response (SCR) and unconditioned stimulus (UCS) expectancy were
      measured concurrently as participants were exposed to a differential delay fear
      conditioning procedure in which one tone (CS+) predicted a loud white noise,
      whereas a second tone (CS-) was presented alone. UCS predictability was varied on
      a trial-by-trial basis by presenting conditioned stimuli (CSs) at volumes just
      above or below the perceptual threshold. Differential UCS expectancy (awareness)
      was observed only on perceived trials, whereas differential SCR developed on both
      perceived and unperceived trials. Although perceived stimuli elicited larger
      SCRs, the magnitude of conditioning, indexed by differential conditioned response
      expression (conditioned SCR to CS+ minus the SCR to CS-), was not influenced by
      stimulus perception. These data indicate that conditional fear can be expressed
      when individuals are unaware of fear-eliciting stimuli and suggest that the
      degree of conditioning is independent of awareness during differential Pavlovian
      fear conditioning.

PMID- 14657357
TI  - Contrasting dynamics in the same plant-herbivore interaction.
AB  - Long-term studies of two-species interactions under field conditions are unusual;
      most long-term field studies are of single species dynamics (1-6). Concurrent
      long-term studies on the dynamics of the same two interacting species in
      different locations are very rare. This result has led to the tacit assumption
      that different cases of the same two-species interaction would involve
      essentially quantitative differences (e.g., context-specific differences in the
      numeric values of demographic parameters like fecundity or death rates). Here, we
      show that for one of the best-known two-species systems (ragwort and cinnabar
      moth), this finding does not hold. The interaction between the plant and its
      herbivore is fundamentally different in coastal dunes in The Netherlands and in
      grasslands in Southeast England. In the first case, the dynamics are cyclic and
      the interaction involves both direct and delayed density dependence; in the
      second case, the insect has little impact on plant dynamics and there are no time
      lags in density dependence. The difference is caused by differences in the
      importance of seed-limitation in plant recruitment in the two locations.

PMID- 14657358
TI  - A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents.
AB  - Chronic infection with the protozoan parasite Trypanosoma cruzi is a major cause
      of morbidity and mortality in Latin America. Drug treatments for the associated
      illness, Chagas disease, are toxic and frequently unsuccessful. In a screening
      effort against the drug target protein farnesyltransferase, we identified a
      series of disubstituted imidazoles with highly potent anti-T. cruzi activity that
      apparently acted through a mechanism independent of protein farnesylation.
      Metabolic labeling studies of T. cruzi suggested that sterol biosynthesis was
      inhibited. Combined GC/MS analysis confirmed depletion of cellular sterols and
      suggested that the site of action was sterol 14-demethylase, a cytochrome P450
      enzyme. Spectral studies with recombinant T. cruzi sterol 14-demethylase
      demonstrated that the compounds bind directly to this enzyme. Two of the
      compounds were well absorbed when given orally to mice, gave sustained plasma
      levels, and were well tolerated. The compounds were administered orally to mice
      with acute T. cruzi infection and caused dramatic decrease in parasitemia and led
      to 100% survival. These disubstituted imidazole compounds can be prepared by a
      relatively short synthetic route and represent a structural class with potent
      anti-T. cruzi activity.

PMID- 14657359
TI  - The linear process of somatic evolution.
AB  - Cancer is the consequence of an unwanted evolutionary process. Cells receive
      mutations that alter their phenotype. Especially dangerous are those mutations
      that increase the net reproductive rate of cells, thereby leading to neoplasia
      and later to cancer. The standard models of evolutionary dynamics consider well
      mixed populations of individuals in symmetric positions. Here we introduce a
      spatially explicit, asymmetric stochastic process that captures the essential
      architecture of evolutionary dynamics operating within tissues of multicellular
      organisms. The "linear process" has the property of cancelling out selective
      differences among cells yet retaining the protective function of apoptosis. This
      design can slow down the rate of somatic evolution dramatically and therefore
      delay the onset of cancer.

PMID- 14657360
TI  - Fungal farming in a snail.
AB  - Mutualisms between fungi and fungus-growing animals are model systems for
      studying coevolution and complex interactions between species. Fungal growing
      behavior has enabled cultivating animals to rise to major ecological importance,
      but evolution of farming symbioses is thought to be restricted to three
      terrestrial insect lineages. Surveys along 2,000 km of North America's Atlantic
      coast documented that the marine snail Littoraria irrorata grazes fungus-infected
      wounds on live marsh grass throughout its range. Field experiments demonstrate a
      facultative, farming mutualism between Littoraria and intertidal fungi. Snails
      graze live grass primarily not to feed but to prepare substrate for fungal growth
      and consume invasive fungi. Fungal removal experiments show that snails and fungi
      act synergistically to suppress marsh grass production. These results provide a
      case of fungus farming in the marine environment and outside the class Insecta
      and reveal a previously undemonstrated ecological mechanism (i.e., facilitation
      of fungal invasion) by which grazers can exert top-down control of marine plant
      production.

PMID- 14657361
TI  - Determination of the substrate-docking site of protein tyrosine kinase C-terminal
      Src kinase.
AB  - Protein tyrosine kinases (PTK) are key enzymes of mammalian signal transduction.
      For the fidelity of signal transduction, each PTK phosphorylates only one or a
      few proteins on specific Tyr residues. Substrate specificity is thought to be
      mediated by PTK-substrate docking interactions and recognition of the
      phosphorylation site sequence by the kinase active site. However, a substrate
      docking site has not been determined on any PTK. C-terminal Src kinase (Csk) is a
      PTK that specifically phosphorylates Src family kinases on a C-terminal Tyr. In
      this study, by sequence alignment and site-specific mutagenesis, we located a
      substrate-docking site on Csk. Mutations in the docking site disabled Csk to
      phosphorylate, regulate, and complex with Src but only moderately affected its
      general kinase activity. A peptide mimicking the docking site potently inhibited
      (IC50 = 21 microM) Csk phosphorylation of Src but only moderately inhibited (IC50
      = 422 microM) its general kinase activity. Determination of the substrate-docking
      site provides the structural basis of substrate specificity in Csk and a model
      for understanding substrate specificity in other PTKs.

PMID- 14657362
TI  - CD24 is a genetic modifier for risk and progression of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology,
      but a genetic basis for the disease is undisputed. We have reported that CD24 is
      required for the pathogenicity of autoreactive T cells in experimental autoimmune
      encephalomyelitis, the mouse model of MS. Here we investigate the contribution of
      CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS
      patients and 207 population controls. This single-nucleotide polymorphism results
      in replacement of alanine (CD24a) with valine (CD24v) in the mature protein. We
      found that the CD24v/v renders a >2-fold increase in the relative risk of MS in
      the general population (P = 0.023). Among familial MS, the CD24v allele is
      preferentially transmitted into affected individuals (P = 0.017). Furthermore,
      50% of CD24v/v patients with expanded disability status scale 6.0 reached the
      milestone in 5 years, whereas the CD24a/v (P = 0.00037) and CD24a/a (P = 0.0016)
      patients did so in 16 and 13 years, respectively. Moreover, our data suggest that
      the CD24v/v patients expressed higher levels of CD24 on peripheral blood T cells
      than did the CD24a/a patients. Transfection with CD24a and CD24v cDNA
      demonstrated that the CD24v allele can be expressed at higher efficiency than the
      CD24a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility
      and progression of MS in the central Ohio cohort that we studied, perhaps by
      affecting the efficiency of CD24 expression on the cell surface.

PMID- 14657363
TI  - Identification and molecular characterization of the G alpha12-Rho guanine
      nucleotide exchange factor pathway in Caenorhabditis elegans.
AB  - G alpha 12/13-mediated pathways have been shown to be involved in various
      fundamental cellular functions in mammalian cells such as axonal guidance,
      apoptosis, and chemotaxis. Here, we identified a homologue of Rho-guanine
      nucleotide exchange factor (GEF) in Caenorhabditis elegans (CeRhoGEF), which
      functions downstream of gpa-12, the C. elegans homologue of G alpha 12/13.
      CeRhoGEF contains a PSD-95/Dlg/ZO-1 domain and a regulator of G protein signaling
      (RGS) domain upstream of the Dbl homology-pleckstrin homology region similar to
      mammalian RhoGEFs with RGS domains, PSD-95/Dlg/ZO-1-RhoGEF and leukemia
      associated RhoGEF. It has been shown in mammalian cells that these RhoGEFs
      interact with activated forms of G alpha 12 or G alpha 13 through their RGS
      domains. We demonstrated by coimmunoprecipitation that the RGS domain of CeRhoGEF
      interacts with GPA-12 in an AIF4- activation-dependent manner and confirmed that
      the Dbl homology-pleckstrin homology domain of CeRhoGEF was capable of Rho
      dependent signaling. These results proved conservation of the G alpha 12-RhoGEF
      pathway in C. elegans. Expression of DsRed or GFP under the control of the
      promoter of CeRhoGEF or gpa-12 revealed an overlap of their expression patterns
      in ventral cord motor neurons and several neurons in the head. RNA-mediated gene
      interference for CeRhoGEF and gpa-12 resulted in similar phenotypes such as
      embryonic lethality and sensory and locomotive defects in adults. Thus, the G
      alpha 12/13-RhoGEF pathway is likely to be involved in embryonic development and
      neuronal function in C. elegans.

PMID- 14657364
TI  - Human Mps1 protein kinase is required for centrosome duplication and normal
      mitotic progression.
AB  - The mitotic spindle is essential for the maintenance of genetic stability, and in
      budding yeast its assembly and function depend on the Mps1 protein kinase. Mps1p
      is required for centrosome duplication and the spindle checkpoint. Several recent
      reports demonstrate that vertebrate Mps1 proteins regulate the spindle
      checkpoint, but reports conflict regarding their role in centrosome duplication.
      Here we provide multiple lines of evidence that the human Mps1 protein (hMps1) is
      required for centrosome duplication. A recently described rabbit polyclonal
      antibody against hMps1 specifically recognizes centrosomes in a variety of human
      cell types. Overexpression of a dominant-negative version of hMps1 (hMps1KD) can
      prevent centrosome duplication in a variety of cell types, and active hMps1
      accelerates centrosome reduplication in U2OS cells. Finally, we demonstrate that
      disruption of hMps1 function with pools of hMps1-specific small interfering RNAs
      causes a pleiotropic phenotype resulting from the combination of severe mitotic
      abnormalities and failures in centrosome duplication. This approach demonstrates
      that hMps1 is required for centrosome duplication and for the normal progression
      of mitosis, and suggests that the threshold level of hMps1 function required for
      centrosome duplication is lower than that required for hMps1 mitotic functions.

PMID- 14657365
TI  - Crystal structure of human alpha-tocopherol transfer protein bound to its ligand:
      implications for ataxia with vitamin E deficiency.
AB  - Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central role in
      vitamin E homeostasis, preventing degradation of alpha-T by routing this
      lipophilic molecule for secretion by hepatocytes. Mutations in the gene encoding
      ATTP have been shown to cause a severe deficiency in alpha-T, which results in a
      progressive neurodegenerative spinocerebellar ataxia, known as ataxia with
      vitamin E deficiency (AVED). We have determined the high-resolution crystal
      structure of human ATTP with (2R,4'R,8'R)-alpha-T in the binding pocket.
      Surprisingly, the ligand is sequestered deep in the hydrophobic core of the
      protein, implicating a large structural rearrangement for the entry and release
      of alpha-T. A comparison to the structure of a related protein, Sec14p,
      crystallized without a bona fide ligand, shows a possibly relevant open
      conformation for this family of proteins. Furthermore, of the known mutations
      that cause AVED, one mutation, L183P, is located directly in the binding pocket.
      Finally, three mutations associated with AVED involve arginine residues that are
      grouped together on the surface of ATTP. We propose that this positively charged
      surface may serve to orient an interacting protein, which might function to
      regulate the release of alpha-T through an induced change in conformation of
      ATTP.

PMID- 14657366
TI  - Hyperactivated sperm motility driven by CatSper2 is required for fertilization.
AB  - Elevations of sperm Ca2+ seem to be responsible for an asymmetric form of
      motility called hyperactivation, which is first seen near the time of
      fertilization. The mechanism by which intracellular Ca2+ concentrations increase
      remains unknown despite considerable investigation. Although several prototypical
      voltage-gated calcium channels are present in spermatozoa, they are not essential
      for motility. Furthermore, the forward velocity and percentage of motility of
      spermatozoa are associated with infertility, but their importance relative to
      hyperactivation also remains unknown. We show here that disruption of the gene
      for a recently described sperm-specific voltage-gated cation channel, CatSper2,
      fails to significantly alter sperm production, protein tyrosine phosphorylation
      that is associated with capacitation, induction of the acrosome reaction, forward
      velocity, or percentage of motility, yet CatSper2-/- males are completely
      infertile. The defect that we identify in the null sperm cells is a failure to
      acquire hyperactivated motility, which seems to render spermatozoa incapable of
      generating the "power" needed for penetration of the extracellular matrix of the
      egg. A loss of power is suggested also by experiments in which the viscosity of
      the medium was increased after incubation of spermatozoa in normal capacitating
      conditions. In high-viscosity medium, CatSper2-null spermatozoa lost the ability
      to swim forward, whereas wild-type cells continued to move forward. Thus,
      CatSper2 is responsible for driving hyperactivated motility, and, even with
      typical sperm forward velocities, fertilization is not possible in the absence of
      this highly active form of motility.

PMID- 14657367
TI  - Coding potential of laboratory and clinical strains of human cytomegalovirus.
AB  - Six strains of human cytomegalovirus have been sequenced, including two
      laboratory strains (AD169 and Towne) that have been extensively passaged in
      fibroblasts and four clinical isolates that have been passaged to a limited
      extent in the laboratory (Toledo, FIX, PH, and TR). All of the sequenced viral
      genomes have been cloned as infectious bacterial artificial chromosomes. A total
      of 252 ORFs with the potential to encode proteins have been identified that are
      conserved in all four clinical isolates of the virus. Multiple sequence
      alignments revealed substantial variation in the amino acid sequences encoded by
      many of the conserved ORFs.

PMID- 14657368
TI  - Neural correlates of the emergence of consciousness of thirst.
AB  - Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4
      ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and
      four by functional MRI (fMRI). PET images were made 25 min after beginning
      infusion, when the sensation of thirst began to enter the stream of
      consciousness. The fMRI images were made when the maximum rate of increase of
      thirst occurred. The PET results showed regional cerebral blood flow changes
      similar to those delineated when thirst was maximal. These loci involved the
      phylogenetically ancient areas of the brain. fMRI showed activation in the
      anterior wall of the third ventricle, an area that is key in the genesis of
      thirst but is not an area revealed by PET imaging. Thus, this region plays as
      major a role in thirst for humans as for animals. Strong activations in the brain
      with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and
      middle frontal gyri, insula, and cerebellum. When the subjects drank water to
      satiation, thirst declined immediately to baseline. A precipitate decline in
      intensity of activation signal occurred in the anterior cingulate area (Brodmann
      area 32) putatively related to consciousness of thirst. The intensity of
      activation in the anterior wall of the third ventricle was essentially unchanged,
      which is consistent with the fact that a significant time (15-20 min) would be
      needed before plasma Na concentration changed as a result of water absorption
      from the gut.

PMID- 14657369
TI  - Rapid Ca2+-dependent decrease of protein ubiquitination at synapses.
AB  - Protein ubiquitination has been implicated in the regulation of axonal growth and
      synaptic plasticity as well as in the pathogenesis of neurodegenerative diseases.
      Here we show that depolarization-dependent Ca2+ influx into synaptosomes produces
      a global, rapid (range of seconds), and reversible decrease of the ubiquitinated
      state of proteins, which correlates with the Ca2+-dependent dephosphorylation of
      several synaptic proteins. A similar general decrease in protein ubiquitination
      was observed in nonneuronal cells on Ca2+ entry induced by ionomycin. Both in
      synaptosomes and in nonneuronal cells, this decrease was blocked by FK506 (a
      calcineurin antagonist). Proteins whose ubiquitinated state was decreased include
      epsin 1, a substrate for the deubiquitinating enzyme fat facets/FAM, which we
      show here to be concentrated at synapses. These results reveal a fast regulated
      turnover of protein ubiquitination. In nerve terminals, protein ubiquitination
      may play a role both in the regulation of synaptic function, including vesicle
      traffic, and in the coordination of protein turnover with synaptic use.

PMID- 14657370
TI  - Labeled cortical mantle distance maps of the cingulate quantify differences
      between dementia of the Alzheimer type and healthy aging.
AB  - The cingulate gyri in 37 subjects with and without early dementia of the
      Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution.
      Groups were segregated into young controls (n = 10), age-matched normal controls
      (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated
      Bayesian segmentation of the cortex and gray matter/white matter (GM/WM)
      isosurface generation, tissue compartments were labeled into gray, white, and
      cerebrospinal fluid as a function of distance from the GM/WM isosurface. Cortical
      mantle distance maps are generated profiling the GM volume and cortical mantle
      distribution as a function of distance from the cortical surface. Probabilistic
      tests based on generalizations of Wilcoxon-Mann-Whitney tests were applied to
      quantify cortical mantle distribution changes with normal and abnormal aging. We
      find no significant change between young controls and healthy aging as measured
      by the GM volume and cortical mantle distribution as a function of distance in
      both anterior and posterior regions of the cingulate. Significant progression of
      GM loss is seen in the very mild DAT and mild DAT groups in all areas of the
      cingulate. Posterior regions show both GM volume loss as well as significant
      cortical mantle distribution decrease with the onset of mild DAT. The "shape of
      the cortical mantle" as measured by the cortical mantle distance profiles
      manifests a pronounced increase in variability with mild DAT.

PMID- 14657371
TI  - Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria.
AB  - The low level of oxygenation within tumors is a major cause of radiation
      treatment failures. We theorized that anaerobic bacteria that can selectively
      destroy the hypoxic regions of tumors would enhance the effects of radiation. To
      test this hypothesis, we used spores of Clostridium novyi-NT to treat
      transplanted tumors in mice. The bacteria were found to markedly improve the
      efficacy of radiotherapy in several of the mouse models tested. Enhancement was
      noted with external beam radiation derived from a Cs-137 source, systemic
      radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously
      undescribed form of experimental brachytherapy using plaques loaded with I-125
      seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens,
      and the combination resulted in long-term remissions in a significant fraction of
      animals.

PMID- 14657372
TI  - Chlorophyll breakdown: pheophorbide a oxygenase is a Rieske-type iron-sulfur
      protein, encoded by the accelerated cell death 1 gene.
AB  - Chlorophyll (chl) breakdown during senescence is an integral part of plant
      development and leads to the accumulation of colorless catabolites. The loss of
      green pigment is due to an oxygenolytic opening of the porphyrin macrocycle of
      pheophorbide (pheide) a followed by a reduction to yield a fluorescent chl
      catabolite. This step is comprised of the interaction of two enzymes, pheide a
      oxygenase (PaO) and red chl catabolite reductase. PaO activity is found only
      during senescence, hence PaO seems to be a key regulator of chl catabolism.
      Whereas red chl catabolite reductase has been cloned, the nature of PaO has
      remained elusive. Here we report on the identification of the PaO gene of
      Arabidopsis thaliana (AtPaO). AtPaO is a Rieske-type iron-sulfur cluster
      containing enzyme that is identical to Arabidopsis accelerated cell death 1 and
      homologous to lethal leaf spot 1 (LLS1) of maize. Biochemical properties of
      recombinant AtPaO were identical to PaO isolated from a natural source.
      Production of fluorescent chl catabolite-1 required ferredoxin as an electron
      source and both substrates, pheide a and molecular oxygen. By using a maize lls1
      mutant, the in vivo function of PaO, i.e., degradation of pheide a during
      senescence, could be confirmed. Thus, lls1 leaves stayed green during dark
      incubation and accumulated pheide a that caused a light-dependent lesion mimic
      phenotype. Whereas proteins were degraded similarly in wild type and lls1, a chl
      binding protein was selectively retained in the mutant. PaO expression correlated
      positively with senescence, but the enzyme appeared to be post-translationally
      regulated as well.

PMID- 14657373
TI  - The population structure of Mycobacterium bovis in Great Britain: clonal
      expansion.
AB  - We have analyzed 11,500 isolates of Mycobacterium bovis (the cause of
      tuberculosis in cattle and other mammals) isolated in Great Britain (England,
      Wales and Scotland)] and characterized by spoligotype. Genetic exchange between
      cells is rare or absent in strains of the Mycobacterium tuberculosis complex so
      that, by using spoligotypes, it is possible to recognize "clones" with a recent
      common ancestor. The distribution of variable numbers of tandem repeats types in
      the most common clone in the data set is incompatible with random mutation and
      drift. The most plausible explanation is a series of "clonal expansions," and
      this interpretation is supported by the geographical distribution of different
      genotypes. We suggest that the clonal expansion of a genotype is caused either by
      the spread of a favorable mutation, together with all other genes present in the
      ancestral cell in which the mutation occurred, or by the invasion of a novel
      geographical region by a limited number of genotypes. A similar pattern is
      observed in M. tuberculosis (the main cause of tuberculosis in humans). The
      significance of clonal expansion in other bacteria that have recombination is
      discussed.

PMID- 14657374
TI  - Structures and relative free energies of partially folded states of proteins.
AB  - The ability of proteins to fold to well defined compact structures is one of the
      most remarkable examples of the effect of natural selection on biological
      molecules. To understand their properties, including the stability, the mechanism
      of folding, and the possibilities of misfolding and association, it is necessary
      to know the protein free energy landscape. We use NMR data as restraints in a
      Monte Carlo sampling procedure to determine the ensemble of structures populated
      by human alpha-lactalbumin in the presence of increasing concentrations of urea.
      The ensembles of structures that represent the partially folded states of the
      protein show that two structural cores, corresponding to portions of the alpha
      and beta domains of the native protein, are preserved even when the native-like
      interactions that define their existence are substantially weakened. Analysis of
      the network of residual contacts reveals the presence of a complex interface
      region between the two structural cores and indicates that the development of
      specific interactions within this interface is the key step in achieving the
      native structure. The relative probabilities of the conformations determined from
      the NMR data are used to construct a coarse-grained free energy landscape for
      alpha-lactalbumin in the absence of urea. The form of the landscape, together
      with the existence of distinct cores, supports the concept that robustness and
      modularity are the properties that make possible the folding of complex proteins.

PMID- 14657375
TI  - Random Boolean network models and the yeast transcriptional network.
AB  - The recently measured yeast transcriptional network is analyzed in terms of
      simplified Boolean network models, with the aim of determining feasible rule
      structures, given the requirement of stable solutions of the generated Boolean
      networks. We find that, for ensembles of generated models, those with canalyzing
      Boolean rules are remarkably stable, whereas those with random Boolean rules are
      only marginally stable. Furthermore, substantial parts of the generated networks
      are frozen, in the sense that they reach the same state, regardless of initial
      state. Thus, our ensemble approach suggests that the yeast network shows highly
      ordered dynamics.

PMID- 14657376
TI  - Single-molecule studies of SNARE complex assembly reveal parallel and
      antiparallel configurations.
AB  - Vesicle fusion in eukaryotes is thought to involve the assembly of a highly
      conserved family of proteins termed soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNAREs) into a highly stable parallel four-helix
      bundle. We have used intermolecular single-molecule fluorescence resonance energy
      transfer to characterize preassembled neuronal SNARE complexes consisting of
      syntaxin, synaptobrevin, and synaptosome-associated protein of 25 kDa on
      deposited lipid bilayers. Surprisingly, we found a mixture of parallel as well as
      antiparallel configurations involving the SNARE motifs of syntaxin and
      synaptobrevin as well as those of syntaxin and synaptosome-associated protein of
      25 kDa. The subpopulation with the parallel four-helix bundle configuration could
      be greatly enriched by an additional purification step in the presence of
      denaturant, indicating that the parallel configuration is the energetically most
      favorable state. Interconversion between the configurations was not observed.
      From this observation, we infer the conversion rate to be <1.5 h-1. The existence
      of antiparallel configurations suggests a regulatory role of chaperones, such as
      N-ethylmaleimide-sensitive factor, or the membrane environment during SNARE
      complex assembly in vivo, and it could be a partial explanation for the
      relatively slow rates of vesicle fusion observed by reconstituted fusion
      experiments in vitro.

PMID- 14657377
TI  - A detailed predictive model of the mammalian circadian clock.
AB  - Experimental data on the circadian (approximately 24-h) clock in mammalian cells
      are vast, diverse, and detailed. Mathematical models are therefore needed to
      piece these data together and to study overall clock behavior. Previous models
      have focused on Neurospora or Drosophila or can be converted to a Drosophila
      model simply by renaming variables. Those models used Hill-type terms for
      transcription regulation and Michaelis-Menten type or delay terms for
      posttranslation regulation. Recent mammalian experimental data call into question
      some of the assumptions in these approaches. Moreover, gene duplication has led
      to more proteins in the mammalian system than in lower organisms. Here we develop
      a detailed distinctly mammalian model by using mass action kinetics. Parameters
      for our model are found from experimental data by using a coordinate search
      method. The model accurately predicts the phase of entrainment, amplitude of
      oscillation, and shape of time profiles of clock mRNAs and proteins and is also
      robust to parameter changes and mutations.

PMID- 14657378
TI  - Recursions for statistical multiple alignment.
AB  - Algorithms are presented that allow the calculation of the probability of a set
      of sequences related by a binary tree that have evolved according to the Thorne
      Kishino-Felsenstein model for a fixed set of parameters. The algorithms are based
      on a Markov chain generating sequences and their alignment at nodes in a tree.
      Depending on whether the complete realization of this Markov chain is decomposed
      into the first transition and the rest of the realization or the last transition
      and the first part of the realization, two kinds of recursions are obtained that
      are computationally similar but probabilistically different. The running time of
      the algorithms is O(Pi id=1 Li), where Li is the length of the ith observed
      sequences and d is the number of sequences. An alternative recursion is also
      formulated that uses only a Markov chain involving the inner nodes of a tree.

PMID- 14657379
TI  - HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune
      responses.
AB  - CD4+ T cells are required for immunity against many viral infections, including
      HIV-1 where a positive correlation has been observed between strong recall
      responses and low HIV-1 viral loads. Some HIV-1-specific CD4+ T cells are
      preferentially infected with HIV-1, whereas others escape infection by unknown
      mechanisms. One possibility is that some CD4+ T cells are protected from
      infection by the secretion of soluble HIV-suppressive factors, although it is not
      known whether these factors are produced during primary antigen-specific
      responses. Here, we show that soluble suppressive factors are produced against
      CXCR4 and CCR5 isolates of HIV-1 during the primary immune response of human CD4+
      T cells. This activity requires antigenic stimulation of naive CD4+ T cells. One
      anti-CXCR4 factor is macrophage-derived chemokine (chemokine ligand 22, CCL22),
      and anti-CCR5 factors include macrophage inflammatory protein-1 alpha (CCL3),
      macrophage inflammatory protein-1 beta (CCL4), and RANTES (regulated upon
      activation of normal T cells expressed and secreted) (CCL5). Intracellular
      staining confirms that CD3+CD4+ T cells are the source of the prototype HIV-1
      inhibiting chemokines CCL22 and CCL4. These results show that CD4+ T cells
      secrete an evolving HIV-1-suppressive activity during the primary immune response
      and that this activity is comprised primarily of CC chemokines. The data also
      suggest that production of such factors should be considered in the design of
      vaccines against HIV-1 and as a mechanism whereby the host can control infections
      with this virus.

PMID- 14657380
TI  - Control of Bcl-2 expression by reactive oxygen species.
AB  - Reactive oxygen species (ROS) mediate apoptosis in many different cell types. We
      have previously shown that the antioxidant Mn(III) tetrakis(5,10,15,20-benzoic
      acid)porphyrin (MnTBAP) decreased intracellular ROS and prevented the apoptosis
      of activated T cells in vitro. To determine the mechanism(s) by which MnTBAP
      afforded such protection, we used Affymetrix (Santa Clara, CA) gene arrays to
      compare gene expression in T cells activated with staphylococcal enterotoxin B in
      vivo then cultured with or without MnTBAP. This analysis showed that the
      antioxidant increased the expression of Bcl-2, an antiapoptotic molecule whose
      levels are normally decreased by T cell activation. Culture with MnTBAP revealed
      a tight inverse correlation between the levels of Bcl-2 and ROS within T cells.
      In vivo, production of ROS in activated T cells occurred before Bcl-2 down
      regulation. Furthermore, MnTBAP's ability to prevent death required the
      expression of Bcl-2 in most T cells. Finally, neither ROS production nor the
      effects on Bcl-2 expression required Bim, the Bcl-2 antagonist that mediates the
      death of activated T cells in vivo. Taken together, our results suggest that ROS
      sensitize T cells to apoptosis by decreasing expression of Bcl-2.

PMID- 14657381
TI  - Buoyancy-driven flow in a peat moss layer as a mechanism for solute transport.
AB  - Transport of nutrients, CO2, methane, and oxygen plays an important ecological
      role at the surface of wetland ecosystems. A possibly important transport
      mechanism in a water-saturated peat moss layer (usually Sphagnum cuspidatum) is
      nocturnal buoyancy flow, the downward flow of relatively cold surface water, and
      the upward flow of warm water induced by nocturnal cooling. Mathematical
      stability analysis showed that buoyancy flow occurs in a cooling porous layer if
      the system's Rayleigh number (Ra) exceeds 25. For a temperature difference of 10
      K between day and night, a typical Ra value for a peat moss layer is 80, which
      leads to quickly developing buoyancy cells. Numerical simulation demonstrated
      that fluid flow leads to a considerable mixing of water. Temperature measurements
      in a cylindrical peat sample of 50-cm height and 35-cm diameter were in agreement
      with the theoretical results. The nocturnal flow and the associated mixing of the
      water represent a mechanism for solute transport in water-saturated parts of peat
      land and in other types of terrestrializing vegetation. This mechanism may be
      particularly important in continental wetlands, where Ra values in summer are
      often much larger than the threshold for fluid flow.

PMID- 14657382
TI  - Transforming growth factor beta1 induction of vascular endothelial growth factor
      receptor 1: mechanism of pericyte-induced vascular survival in vivo.
AB  - Degeneration of vessels precedes and precipitates the devastating ischemia of
      many diseases, including retinopathy of prematurity and diabetic retinopathy.
      Ischemia then leads to proliferative retinopathy and blindness. Understanding the
      mechanisms of blood vessel degeneration is critical to prevention of these
      diseases. Vessel loss is associated with oxygen-induced suppression of vascular
      endothelial growth factor (VEGF) and with pericyte (vascular smooth muscle cell)
      dropout. The molecular mechanism of pericyte protection of the vasculature is
      unknown. We show that transforming growth factor beta1 (TGF-beta1)-expressing
      pericytes are specifically found on vessels resistant to oxygen-induced loss. TGF
      beta1 potently induces VEGF receptor 1 (VEGFR-1) expression in endothelial cells
      and thereby prevents oxygen-induced vessel loss in vivo. Vessel survival is
      further stimulated with a VEGFR-1-specific ligand, placental growth factor 1. TGF
      beta1 induction of VEGFR-1 in endothelial cells explains pericyte protection of
      vessels and the selective vulnerability of neonatal vessels to oxygen. These
      results implicate induction and activation of VEGFR-1 as critical targets to
      prevent vessel loss.

PMID- 14657383
TI  - Induced-fit recognition of DNA by organometallic complexes with dynamic
      stereogenic centers.
AB  - Organometallic chemistry offers novel concepts in structural diversity and
      molecular recognition that can be used in drug design. Here, we consider DNA
      recognition by eta 6-arene Ru(II) anticancer complexes by an induced-fit
      mechanism. The stereochemistry of the dinuclear complex [((eta 6
      biphenyl)RuCl(en))2-(CH2)6]2 + (3, en = ethylenediamine) was elucidated by
      studies of the half unit [(eta 6-biphenyl)RuCl(Et-en)]+ (2, where Et-en is
      Et(H)NCH2CH2NH2). The structures of the separated RRu*RN* and SRu*RN*
      diastereomers of 2 were determined by x-ray crystallography; their slow
      interconversion in water (t(1/2) approximately 2 h, 298 K, pH 6.2) was observed
      by NMR spectroscopy. For 2 and 3 the RRu*RN* configurations are more stable than
      SRu*RN* (73:27). X-ray and NMR studies showed that reactions of 2 and 3 with 9
      ethylguanine gave rise selectively to SRu*RN* diastereomers. Dynamic chiral
      recognition of guanine can lead to high diastereoselectivity of DNA binding. The
      dinuclear complex 3 induced a large unwinding (31 degrees) of plasmid DNA, twice
      that of mononuclear 2 (14 degrees), and effectively inhibited DNA-directed RNA
      synthesis in vitro. This dinuclear complex gave rise to interstrand cross-links
      on a 213-bp plasmid fragment with efficiency similar to bifunctional cisplatin,
      and to 1,3-GG interstrand and 1,2-GG and 1,3-GTG intrastrand cross-links on site
      specifically ruthenated 20-mers. Complex 3 blocked intercalation of ethidium
      considerably more than mononuclear 2. The concept of induced-fit recognition of
      DNA by organometallic complexes containing dynamic stereogenic centers via
      dynamic epimerization, intercalation, and cross-linking may be useful in the
      design of anticancer drugs.

PMID- 14657384
TI  - CD4 T cell memory derived from young naive cells functions well into old age, but
      memory generated from aged naive cells functions poorly.
AB  - Age-related declines in immune function have an impact on both primary and memory
      responses. In this study, we have examined the ability of naive CD4 T cells from
      young and aged T cell receptor transgenic mice to establish functional memory. We
      found that memory cells generated from young CD4 T cells responded well to
      antigen, even a year after generation, whereas memory cells derived from CD4 T
      cells from aged mice responded poorly both ex vivo and in vivo. Memory cells
      generated from aged naive cells proliferate less, produce reduced levels of
      cytokines, and exhibit reduced cognate helper function, compared with memory
      cells generated by using young naive cells. These results indicate that it is the
      age of the naive T cell when it first encounters antigen, rather than the age
      when it reencounters antigen, that is critical for good memory CD4 T cell
      function.

PMID- 14657385
TI  - NMR-detected hydrogen exchange and molecular dynamics simulations provide
      structural insight into fibril formation of prion protein fragment 106-126.
AB  - PrP106-126, a peptide corresponding to residues 107-127 of the human prion
      protein, induces neuronal cell death by apoptosis and causes proliferation and
      hypertrophy of glia, reproducing the main neuropathological features of prion
      related transmissible spongiform encephalopathies, such as bovine spongiform
      encephalopathy and Creutzfeldt-Jakob disease. Although PrP106-126 has been shown
      to form amyloid-like fibrils in vitro, their structural properties have not been
      elucidated. Here, we investigate the conformational characteristics of a fibril
      forming fragment of the mouse prion protein, MoPrP106-126, by using electron
      microscopy, CD spectroscopy, NMR-detected hydrogen-deuterium exchange
      measurements, and molecular dynamics simulations. The fibrils contain
      approximately 50% beta-sheet structure, and strong amide exchange protection is
      limited to the central portion of the peptide spanning the palindromic sequence
      VAGAAAAGAV. Molecular dynamics simulations indicate that MoPrP106-126 in water
      assumes a stable structure consisting of two four-stranded parallel beta-sheets
      that are tightly packed against each other by methyl-methyl interactions. Fibril
      formation involving polyalanine stacking is consistent with the experimental
      observations.

PMID- 14657386
TI  - Lesion bypass DNA polymerases replicate across non-DNA segments.
AB  - A critical feature of the robustness of the DNA replication machinery is the
      ability to complete its task in the presence of interfering DNA damage. A key
      mechanism responsible for this task is translesion replication (also termed
      translesion synthesis), carried out by specialized lesion bypass DNA polymerases
      of the Y superfamily. Here we show that in Escherichia coli, plasmids can be
      replicated across a segment of foreign non-DNA material, consisting of
      hydrocarbon chains of 3 or 12 methylene residues. This replication is carried out
      by DNA polymerase V and proceeds by at least two mechanisms: (i) Editing out the
      foreign insert, by polymerase "hopping" across it, which can be mediated by
      looping out of the insert, leading to its deletion, while preserving the DNA
      sequence. (ii) DNA synthesis through the insert, which occurs by incorporating
      one or two nucleotides opposite the hydrocarbon chain, yielding a net increase in
      the length of the DNA sequence. The remarkable ability of DNA polymerase V to
      insert nucleotides opposite a hydrocarbon chain shows that DNA synthesis can
      occur in a region of the template strand, which lacks all fundamental features of
      DNA, including its purine, pyrimidine, sugar, and phosphate moieties, and its
      hydrophilic and ionic nature. This bypass ability reflects a striking robustness
      of the translesion replication apparatus and is likely to contribute to its
      effectiveness in maintaining genome stability.

PMID- 14657387
TI  - Viral protein U counteracts a human host cell restriction that inhibits HIV-1
      particle production.
AB  - Human cells resist viral infections by a variety of mechanisms. Viruses must
      overcome host cell restrictions to successfully reproduce their genetic material.
      Here, we identify a host restriction to viral replication that acts at the stage
      of particle assembly. Viral protein U (Vpu) is an HIV-1 accessory protein that
      enhances particle assembly and release in most human cells, but not in simian
      cells. By using human-simian cell heterokaryons, we show that the inhibition of
      assembly in human cells is dominant. Vpu overcomes the block to assembly in human
      cells and in human-simian heterokaryons. The HIV-1 vpu gene may have evolved to
      counteract an assembly restriction that is present in human cells.

PMID- 14657388
TI  - The tandem Src homology 2 domain of the Syk kinase: a molecular device that
      adapts to interphosphotyrosine distances.
AB  - Conformational flexibility is important for protein function. However,
      information on the range of conformations accessible to macromolecules in the
      unbound state is often difficult to obtain. By using the model system of the
      tandem Src homology 2 domain (i.e., two adjacent Src homology 2 domains) of the
      Syk kinase, we report a method combining calorimetric and crystallographic
      measurements that reveals the preexistence of a conformational equilibrium in the
      unbound state, and that shows that this equilibrium is crucial for function.

PMID- 14657389
TI  - Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a
      control mechanism for thyroid hormone release.
AB  - Hormone secretion by thyrocytes occurs by fluid phase uptake and lysosomal
      degradation of the prohormone thyroglobulin (Tg). However, some Tg internalized
      by megalin bypasses lysosomes and is transcytosed across cells and released into
      the bloodstream. Because the hormone content of Tg is variable, we investigated
      whether this affects transcytosis. We found that rat Tg with a low hormone
      content [low-hormonogenic rat Tg (low-horm-rTg)] is transcytosed by megalin
      across thyroid FRTL-5 cells to a greater extent than rat Tg with a high hormone
      content [hormonogenic rat Tg (horm-rTg)]. In immunoprecipitation experiments, the
      Tg sequence Arg-2489-Lys-2503 (required for binding to megalin and heparan
      sulfate proteoglycans) was found to be more exposed in low-horm-rTg, which
      accounted for its preferential transcytosis. Thus, removal of surface heparan
      sulfate proteoglycans from FRTL-5 cells or blocking of 2489-2503 reduced
      transcytosis of low-horm-rTg to a greater extent than that of horm-rTg.
      Preferential transcytosis of low-horm-rTg affected hormone release. Thus, the
      increase in hormone release from horm-rTg in FRTL-5 cells determined by megalin
      blocking (due to reduced transcytosis and enhanced Tg degradation) was rescued by
      low-horm-rTg, suggesting that megalin is required for effective hormone release.
      This finding was confirmed in a small number of megalin-deficient mice, which had
      serological features resembling mild hypothyroidism. Reduced hormone formation
      within Tg in vivo, due to treatment of rats with aminotriazole or of patients
      with Graves' disease with methimazole, resulted in increased Tg transcytosis via
      megalin, in confirmation of results with FRTL-5 cells. Our study points to a
      major role of megalin in thyroid homeostasis with possible implications in
      thyroid diseases.

PMID- 14657390
TI  - A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor.
AB  - Peptides bind MHC class I molecules by anchoring hydrophobic side chains into
      pockets in the peptide binding groove. Here, we report an immunogenic (in vitro
      and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully
      crossreactive with the nonglycosylated variant. Molecular modeling showed that
      the central P5-Thr-GalNAc residue points into the C pocket and forms van der
      Waals and hydrogen bond interactions with the MHC class I. As predicted, GalNAc,
      a modified peptide carrying an additional anchor in the central C anchor pocket,
      increased the affinity by approximately 100-fold compared with the native low
      affinity peptide (MUC1-8). The findings demonstrate that glycopeptides associated
      with MHC class I molecules can use GalNAc to anchor the peptide in the groove and
      enable high-affinity binding.

PMID- 14657391
TI  - Thermodynamic stability of hydrogen clathrates.
AB  - The stability of the recently characterized type II hydrogen clathrate [Mao, W.
      L., Mao, H.-K., Goncharov, A. F., Struzhkin, V. V., Guo, Q., et al. (2002)
      Science 297, 2247-2249] with respect to hydrogen occupancy is examined with a
      statistical mechanical model in conjunction with first-principles quantum
      chemistry calculations. It is found that the stability of the clathrate is mainly
      caused by dispersive interactions between H2 molecules and the water forming the
      cage walls. Theoretical analysis shows that both individual hydrogen molecules
      and nH2 guest clusters undergo essentially free rotations inside the clathrate
      cages. Calculations at the experimental conditions--2,000 bar (1 bar = 100 kPa)
      and 250 K confirm multiple occupancy of the clathrate cages with average
      occupations of 2.00 and 3.96 H2 molecules per D-5(12) (small) and H-5(12)6(4)
      (large) cage, respectively. The H2-H2O interactions also are responsible for the
      experimentally observed softening of the H[bond]H stretching modes. The clathrate
      is found to be thermodynamically stable at 25 bar and 150 K.

PMID- 14657392
TI  - Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities
      among a family of poxvirus viroceptors.
AB  - We identify a secreted chemokine inhibitor encoded by orf virus (ORFV), the
      prototypic poxvirus of the Parapoxvirus genus, and show that it is related to the
      poxvirus type II CC-chemokine-binding proteins (CBP-II) produced by members of
      the Orthopoxvirus and Leporipoxvirus genera. The ORFV chemokine-binding protein
      (CBP) is functionally similar to the CBP-II proteins in its ability to bind and
      inhibit many CC-chemokines with high affinity. However, unlike CBP-II, the ORFV
      CBP also binds with high affinity to lymphotactin, a member of the C-chemokine
      family, demonstrating that the ORFV CBP possesses an altered binding specificity.
      Interestingly, the amino acid sequence of ORFV CBP more closely resembles the
      granulocyte-macrophage colony-stimulating factor/IL-2 inhibitory factor also
      produced by ORFV, implicating the granulocyte-macrophage colony-stimulating
      factor/IL-2 inhibitory factor protein as a highly diverged, but related, member
      of the CBP-II protein family. Notably, these findings suggest that the genes that
      encode these proteins derive from a common poxvirus ancestral gene that has since
      been modified in binding specificity during speciation of the poxvirus genera.
      Overall, these findings illustrate the concept of evolution of viral proteins at
      the biophysical and molecular interface.

PMID- 14657393
TI  - A critical role of neural-specific JNK3 for ischemic apoptosis.
AB  - c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress
      induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2,
      and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the
      major isoform responsible for the high level of basal JNK activity in the brain.
      In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK
      activity, but also protects mice from brain injury after cerebral ischemia
      hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the
      induction of Bim and Fas and the mitochondrial release of cytochrome c. These
      results suggest that JNK3 is a potential target for neuroprotection therapies in
      stroke.

PMID- 14657394
TI  - A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites
      formed during catalysis with cytochrome P450scc (CYP11A1).
AB  - Metabolites of vitamin D3 (D3) (cholecalciferol) are recognized as enzymatically
      formed chemicals in humans that can influence a wide variety of reactions that
      regulate a large number of cellular functions. The metabolism of D3 has been
      extensively studied, and a role for three different mitochondrial cytochrome
      P450s (CYP24A, CYP27A, and CYP27B1) has been described that catalyze the
      formation of the 24(OH), 25(OH), and 1(OH) metabolites of D3, respectively. The
      hormone 1,25-dihydroxyvitamin D3 has been most extensively studied and is widely
      recognized as a regulator of calcium and phosphorous metabolism. Hydroxylated
      metabolites of D3 interact with the nuclear receptor and thereby influence
      growth, cellular differentiation, and proliferation. In this article, we describe
      in vitro experiments using purified mitochondrial cytochrome P450scc (CYP11A1)
      reconstituted with the iron-sulfer protein, adrenodoxin, and the flavoprotein,
      adrenodoxin reductase, and show the NADPH and time-dependent formation of two
      major metabolites of D3 (i.e., 20-hydroxyvitamin D3 and 20,22-dihydroxyvitamin
      D3) plus two unknown minor metabolites. In addition, we describe the metabolism
      of 7-dehydrocholesterol by CYP11A1 to a single product identified as 7
      dehydropregnenolone. Although the physiological importance of these hydroxylated
      metabolites of D3 and their in vivo formation and mode of action remain to be
      determined, the rate with which they are formed by CYP11A1 in vitro suggests an
      important role.

PMID- 14657395
TI  - Thermodynamic treatment of oligonucleotide duplex-simplex equilibria.
AB  - Thermodynamic formulations have been devised to obtain Delta G degrees values
      directly from spectroscopic data at a fixed common temperature in nucleic acid
      duplex-simplex melting curves. In addition, the dependence of melting on salt
      concentration has been expressed in terms of a stepwise stoichiometric
      representation, which leads to a specific equation for the partition of the added
      sodium ions between the different oligonucleotide forms.

PMID- 14657396
TI  - A metabolic labeling approach toward proteomic analysis of mucin-type O-linked
      glycosylation.
AB  - Mucin-type O-linked glycoproteins are involved in a variety of biological
      interactions in higher eukaryotes. The biosynthesis of these glycoproteins is
      initiated by a family of polypeptide N-acetyl-alpha-galactosaminyltransferases
      (ppGalNAcTs) that modify proteins in the secretory pathway. The lack of a defined
      consensus sequence for the ppGalNAcTs makes the prediction of mucin-type O-linked
      glycosylation difficult based on primary sequence alone. Herein we present a
      method for labeling mucin-type O-linked glycoproteins with a unique chemical tag,
      the azide, which permits their selective covalent modification from complex cell
      lysates. From a panel of synthetic derivatives, we identified an azido GalNAc
      analog (N-azidoacetylgalactosamine, GalNAz) that is metabolized by numerous cell
      types and installed on mucin-type O-linked glycoproteins by the ppGalNAcTs. The
      azide serves as a bioorthogonal chemical handle for selective modification with
      biochemical or biophysical probes using the Staudinger ligation. The approach was
      validated by labeling a recombinant glycoprotein that is known to possess O
      linked glycans with GalNAz. In addition, GalNAz efficiently labeled mucin-type O
      linked glycoproteins expressed at endogenous levels. The ability to label mucin
      type O-linked glycoproteins with chemical tags should facilitate their
      identification by proteomic strategies.

PMID- 14657397
TI  - Structure and functional significance of mechanically unfolded fibronectin type
      III1 intermediates.
AB  - Fibronectin (FN) forms fibrillar networks coupling cells to the extracellular
      matrix. The formation of FN fibrils, fibrillogenesis, is a tightly regulated
      process involving the exposure of cryptic binding sites in individual FN type III
      (FN-III) repeats presumably exposed by mechanical tension. The FN-III1 module has
      been previously proposed to contain such cryptic sites that promote the assembly
      of extracellular matrix FN fibrils. We have combined NMR and steered molecular
      dynamics simulations to study the structure and mechanical unfolding pathway of
      FN-III1. This study finds that FN-III1 consists of a beta-sandwich structure that
      unfolds to a mechanically stable intermediate about four times the length of the
      native folded state. Considering previous experimental findings, our studies
      provide a structural model by which mechanical stretching of FN-III1 may induce
      fibrillogenesis through this partially unfolded intermediate.

PMID- 14657399
TI  - Generating a synthetic genome by whole genome assembly: phiX174 bacteriophage
      from synthetic oligonucleotides.
AB  - We have improved upon the methodology and dramatically shortened the time
      required for accurate assembly of 5- to 6-kb segments of DNA from synthetic
      oligonucleotides. As a test of this methodology, we have established conditions
      for the rapid (14-day) assembly of the complete infectious genome of
      bacteriophage X174 (5386 bp) from a single pool of chemically synthesized
      oligonucleotides. The procedure involves three key steps: (i). gel purification
      of pooled oligonucleotides to reduce contamination with molecules of incorrect
      chain length, (ii). ligation of the oligonucleotides under stringent annealing
      conditions (55 degrees C) to select against annealing of molecules with incorrect
      sequences, and (iii). assembly of ligation products into full-length genomes by
      polymerase cycling assembly, a nonexponential reaction in which each terminal
      oligonucleotide can be extended only once to produce a full-length molecule. We
      observed a discrete band of full-length assemblies upon gel analysis of the
      polymerase cycling assembly product, without any PCR amplification. PCR
      amplification was then used to obtain larger amounts of pure full-length genomes
      for circularization and infectivity measurements. The synthetic DNA had a lower
      infectivity than natural DNA, indicating approximately one lethal error per 500
      bp. However, fully infectious X174 virions were recovered after electroporation
      into Escherichia coli. Sequence analysis of several infectious isolates verified
      the accuracy of these synthetic genomes. One such isolate had exactly the
      intended sequence. We propose to assemble larger genomes by joining separately
      assembled 5- to 6-kb segments; approximately 60 such segments would be required
      for a minimal cellular genome.

PMID- 14657398
TI  - Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion
      channel TRPM5.
AB  - The transduction of taste is a fundamental process that allows animals to
      discriminate nutritious from noxious substances. Three taste modalities, bitter,
      sweet, and amino acid, are mediated by G protein-coupled receptors that signal
      through a common transduction cascade: activation of phospholipase C beta2,
      leading to a breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) into
      diacylglycerol and inositol 1,4,5-trisphosphate, which causes release of Ca2+
      from intracellular stores. The ion channel, TRPM5, is an essential component of
      this cascade; however, the mechanism by which it is activated is not known. Here
      we show that heterologously expressed TRPM5 forms a cation channel that is
      directly activated by micromolar concentrations of intracellular Ca2+ (K1/2 = 21
      microM). Sustained exposure to Ca2+ desensitizes TRPM5 channels, but PIP2
      reverses desensitization, partially restoring channel activity. Whole-cell TRPM5
      currents can be activated by intracellular Ca2+ and show strong outward
      rectification because of voltage-sensitive gating of the channels. TRPM5 channels
      are nonselective among monovalent cations and not detectably permeable to
      divalent cations. We propose that the regulation of TRPM5 by Ca2+ mediates
      sensory activation in the taste system.

PMID- 14657400
TI  - Targeting Schwann cells by nonlytic arenaviral infection selectively inhibits
      myelination.
AB  - Members of the arenavirus family, famous for their hemorrhagic syndromes, cause
      distinct neurological disorders; however, cellular and molecular targets as well
      as pathogenesis of peripheral nervous system disorders associated with these
      viruses are unknown. Using noncytolytic lymphocytic choriomeningitis virus, the
      prototype arenavirus, and pseudotyped Lassa fever virus, we showed that the
      Schwann cells, but not the neurons, were preferentially targeted and harbored the
      virus. This permissiveness was caused by the viral glycoprotein usage of its
      receptor alpha-dystroglycan, which was highly abundant on Schwann cell membranes.
      Persistent lymphocytic choriomeningitis virus infection rendered immature Schwann
      cells defective or incapable of forming compact myelin sheathes when they
      differentiated to myelinating phenotype in an in vitro differentiation model of
      Schwann cells. Persistent infection did not cause Schwann cell apoptosis or
      cytopathic effect. Defects in myelination coincided with the down-regulation of
      dystroglycan expression and disruption of the laminin-2 organization and basal
      lamina assembly on Schwann cell-axon units. The data provide evidence for a
      selective perturbation of laminin-2-laminin-2 receptor communication pathway in
      the peripheral nervous system by a nonlytic virus and the resulting myelin
      defects, which may partly contribute to neurological abnormalities associated
      with arenaviral infection.

PMID- 14657401
TI  - Induction of salt and osmotic stress tolerance by overexpression of an
      intracellular vesicle trafficking protein AtRab7 (AtRabG3e).
AB  - Adaptation to stress requires removal of existing molecules from various cellular
      compartments and replacing them with new ones. The transport of materials to and
      from the specific compartments involved in the recycling and deposition of
      macromolecules is carried out by an intracellular vesicle trafficking system.
      Here, we report the isolation of a vesicle trafficking-regulating gene, AtRabG3e
      (formerly AtRab7), from Arabidopsis. The gene was induced during programmed cell
      death after treatment of intact leaves with superoxide and salicylic acid or
      infection with necrogenic pathogens. Transgenic plants that expressed the
      AtRabG3e gene under the constitutive 35S promoter from cauliflower mosaic virus
      exhibited accelerated endocytosis in roots, leaves, and protoplasts. The
      transgenic plants accumulated sodium in the vacuoles and had higher amounts of
      sodium in the shoots. The transgenic plants also showed increased tolerance to
      salt and osmotic stresses and reduced accumulation of reactive oxygen species
      during salt stress. These results imply that vesicle trafficking plays an
      important role in plant adaptation to stress, beyond the housekeeping function in
      intracellular vesicle trafficking.

PMID- 14657402
TI  - Functional analysis and intracellular localization of rice cryptochromes.
AB  - Blue-light-receptor cryptochrome (CRY), which mediates cotyledon expansion,
      increased accumulation of anthocyanin, and inhibition of hypocotyl elongation,
      was first identified in Arabidopsis. Two Arabidopsis cryptochromes (AtCRY1 and
      AtCRY2) have been reported to be localized to the nucleus. However, there is no
      information on the cryptochromes in monocotyledons. In this study, we isolated
      two cryptochrome cDNAs, OsCRY1 and OsCRY2, from rice (Oryza sativa) plants. The
      deduced amino acid sequences of OsCRY1 and OsCRY2 have a photolyase-like domain
      in their N termini and are homologous to AtCRY1. To investigate the function of
      OsCRY1, we overexpressed a green fluorescence protein-OsCRY1 fusion gene in
      Arabidopsis and assessed the phenotypes of the resulting transgenic plants. When
      the seedlings were germinated in the dark, no discernible effect was observed.
      However, light-germinated seedlings showed pronounced inhibition of hypocotyl
      elongation and increased accumulation of anthocyanin. These phenotypes were
      induced in a blue-light-dependent manner, indicating that OsCRY1 functions as a
      blue-light-receptor cryptochrome. We also examined the intracellular localization
      of green fluorescence protein-OsCRY1 in the transgenic plants. It was localized
      to both the nucleus and the cytoplasm. We identified two nuclear localization
      domains in the primary structure of OsCRY1. We discuss the relationship between
      the function and intracellular localization of rice cryptochromes by using
      additional data obtained with OsCRY2.

PMID- 14657403
TI  - An invertase inhibitor from maize localizes to the embryo surrounding region
      during early kernel development.
AB  - Invertase activity is thought to play a regulatory role during early kernel
      development by converting sucrose originating from source leaves into hexoses to
      support cell division in the endosperm and embryo. Invertases are regulated at
      the posttranslational level by small protein inhibitors, INVINHs. We found that
      in maize (Zea mays), an invertase inhibitor homolog (ZM-INVINH1) is expressed
      early in kernel development, between 4 and 7 d after pollination. Invertase
      activity is reduced in vitro in the presence of recombinant ZM-INVINH1, and
      inhibition is attenuated by pre-incubation with sucrose. The presence of a
      putative signal peptide, fractionation experiments, and ZM-INVINH1::green
      fluorescent protein fusion experiments indicate that the protein is exported to
      the apoplast. Moreover, association of ZM-INVINH1 with the glycoprotein fraction
      by concanavalin A chromatogaphy suggests that ZM-INVINH1 interacts with an
      apoplastic invertase during early kernel development. ZM-INVINH1 was localized to
      the embryo surrounding region by in situ analysis, suggesting that this region
      forms a boundary, compartmentalizing apoplast invertase activity to allow
      different embryo and endosperm developmental rates.

PMID- 14657404
TI  - Xylem wall collapse in water-stressed pine needles.
AB  - Wall reinforcement in xylem conduits is thought to prevent wall implosion by
      negative pressures, but direct observations of xylem geometry during water stress
      are still largely lacking. In this study, we have analyzed the changes in xylem
      geometry during water stress in needles of four pine species (Pinus spp.).
      Dehydrated needles were frozen with liquid nitrogen, and xylem cross sections
      were observed, still frozen, with a cryo-scanning electron microscope and an
      epifluorescent microscope. Decrease in xylem pressure during drought provoked a
      progressive collapse of tracheids below a specific threshold pressure
      (P(collapse)) that correlates with the onset of cavitation in the stems.
      P(collapse) was more negative for species with smaller tracheid diameter and
      thicker walls, suggesting a tradeoff between xylem efficiency, xylem
      vulnerability to collapse, and the cost of wall stiffening. Upon severe
      dehydration, tracheid walls were completely collapsed, but lumens still appeared
      filled with sap. When dehydration proceeded further, tracheids embolized and
      walls relaxed. Wall collapse in dehydrated needles was rapidly reversed upon
      rehydration. We discuss the implications of this novel hydraulic trait on the
      xylem function and on the understanding of pine water relations.

PMID- 14657405
TI  - Biosynthesis of camptothecin. In silico and in vivo tracer study from [1
      13C]glucose.
AB  - Camptothecin derivatives are clinically used antitumor alkaloids that belong to
      monoterpenoid indole alkaloids. In this study, we investigated the biosynthetic
      pathway of camptothecin from [1-13C]glucose (Glc) by in silico and in vivo
      studies. The in silico study measured the incorporation of Glc into alkaloids
      using the Atomic Reconstruction of Metabolism software and predicted the labeling
      patterns of successive metabolites from [1-13C]Glc. The in vivo study followed
      incorporation of [1-13C]Glc into camptothecin with hairy roots of Ophiorrhiza
      pumila by 13C nuclear magnetic resonance spectroscopy. The 13C-labeling pattern
      of camptothecin isolated from the hairy roots clearly showed that the monoterpene
      secologanin moiety was synthesized via the 2C-methyl-D-erythritol 4-phosphate
      pathway, not via the mevalonate pathway. This conclusion was supported by
      differential inhibition of camptothecin accumulation by the pathway-specific
      inhibitors (fosmidomycin and lovastatin). The quinoline moiety from tryptophan
      was also labeled as predicted by the Atomic Reconstruction of Metabolism program
      via the shikimate pathway. These results indicate that camptothecin is formed by
      the combination of the 2C-methyl-D-erythritol 4-phosphate pathway and the
      shikimate pathway. This study provides the innovative example for how a computer
      aided comprehensive metabolic analysis will refine the experimental design to
      obtain more precise biological information.

PMID- 14657406
TI  - A large complement of the predicted Arabidopsis ARM repeat proteins are members
      of the U-box E3 ubiquitin ligase family.
AB  - The Arabidopsis genome was searched to identify predicted proteins containing
      armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in
      a number of different animal proteins. Using domain database predictions and
      models generated in this study, 108 Arabidopsis proteins were identified that
      contained a minimum of two ARM repeats with the majority of proteins containing
      four to eight ARM repeats. Clustering analysis showed that the 108 predicted
      Arabidopsis ARM repeat proteins could be divided into multiple groups with wide
      differences in their domain compositions and organizations. Interestingly, 41 of
      the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a
      family of E3 ligases, and these proteins represented the largest class of
      Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there
      was also a novel conserved domain identified in the N-terminal region. Based on
      the phylogenetic tree, representative U-box/ARM repeat proteins were selected for
      further study. RNA-blot analyses revealed that these U-box/ARM proteins are
      expressed in a variety of tissues in Arabidopsis. In addition, the selected U
      box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U
      box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

PMID- 14657407
TI  - A defective signal peptide in a 19-kD alpha-zein protein causes the unfolded
      protein response and an opaque endosperm phenotype in the maize De*-B30 mutant.
AB  - Defective endosperm* (De*)-B30 is a dominant maize (Zea mays) mutation that
      depresses zein synthesis in the developing endosperm. The mutant kernels have an
      opaque, starchy phenotype, malformed zein protein bodies, and highly increased
      levels of binding protein and other chaperone proteins in the endosperm.
      Immunoblotting revealed a novel alpha-zein protein in De*-B30 that migrates
      between the 22- and 19-kD alpha-zein bands. Because the De*-B30 mutation maps in
      a cluster of 19-kD alpha-zein genes, we characterized cDNA clones encoding these
      proteins from a developing endosperm library. This led to the identification of a
      19-kD alpha-zein cDNA in which proline replaces serine at the 15th position of
      the signal peptide. Although the corresponding gene does not appear to be highly
      expressed in De*-B30, it was found to be tightly linked with the mutant phenotype
      in a segregating F2 population. Furthermore, when the protein was synthesized in
      yeast cells, the signal peptide appeared to be less efficiently processed than
      when serine replaced proline. To test whether this gene is responsible for the
      De*-B30 mutation, transgenic maize plants expressing this sequence were created.
      T1 seeds originating from the transformants manifested an opaque kernel phenotype
      with enhanced levels of binding protein in the endosperm, similar to De*-B30.
      These results are consistent with the hypothesis that the De*-B30 mutation causes
      a defective signal peptide in a 19-kD alpha-zein protein.

PMID- 14657408
TI  - Molecular and cell biology of a family of voltage-dependent anion channel porins
      in Lotus japonicus.
AB  - Voltage-dependent anion channels (VDACs) are generally considered as the main
      pathway for metabolite transport across the mitochondrial outer membrane. Recent
      proteomic studies on isolated symbiosome membranes from legume nodules indicated
      that VDACs might also be involved in transport of nutrients between plants and
      rhizobia. In an attempt to substantiate this, we carried out a detailed molecular
      and cellular characterization of VDACs in Lotus japonicus and soybean (Glycine
      max). Database searches revealed at least five genes encoding putative VDACs in
      each of the legumes L. japonicus, Medicago truncatula, and soybean. We obtained
      and sequenced cDNA clones from L. japonicus encoding five full-length VDAC
      proteins (LjVDAC1.1-1.3, LjVDAC2.1, and LjVDAC3.1). Complementation of a yeast
      (Saccharomyces cerevisiae) mutant impaired in VDAC1, a porin of the mitochondrial
      outer membrane, showed that LjVDAC1.1, LjVDAC1.2, LjVDAC2.1, and LjVDAC3.1, but
      not LjVDAC1.3, are functional and targeted to the mitochondrial outer membrane in
      yeast. Studies of the expression pattern of the five L. japonicus VDAC genes
      revealed largely constitutive expression of each throughout the plant, including
      nodules. Antibodies to LjVDAC1.1 of L. japonicus and the related POM36 protein of
      potato (Solanum tuberosum) recognized several proteins between 30 and 36 kD on
      western blots, including LjVDAC1.1, LjVDAC1.2, LjVDAC1.3, and LjVDAC2.1.
      Immunolocalization of VDACs in L. japonicus and soybean root nodules demonstrated
      their presence on not only mitochondria but also on numerous, small vesicles at
      the cell periphery. No evidence was found for the presence of VDACs on the
      symbiosome membrane. Nonetheless, the data indicate that VDACs may play more
      diverse roles in plants than suspected previously.

PMID- 14657409
TI  - Characterization of geraniol synthase from the peltate glands of sweet basil.
AB  - The monoterpene fraction of the lemon-scented sweet basil (Ocimum basilicum) cv
      Sweet Dani consists mostly of citral (a mixture of geranial and neral), with
      lower levels of geraniol and nerol. These compounds are stored in the peltate
      glands found on the leaf epidermis. Younger leaves, which have a higher density
      of such glands, also have a higher content of monoterpenes than older leaves.
      Geraniol synthase (GES) activity, generating geraniol from geranyl diphosphate,
      was shown to be localized exclusively or almost exclusively to glands. GES
      activity resides in a homodimeric protein that was purified to near homogeneity.
      Basil GES requires Mn2+ as a divalent metal cofactor for activity and produces
      only geraniol from geranyl diphosphate. Km values of 21 and 51 microM were
      obtained for geranyl diphosphate and Mn2+, respectively. In the presence of 18O
      labeled water, GES catalyzed the formation of 18O-geraniol from geranyl
      diphosphate, indicating that the reaction mechanism of GES is similar to that of
      other monoterpene synthases and is different from the action of phosphatases. A
      GES cDNA was isolated based on analysis of a glandular trichome expressed
      sequence tag database, and the sequence of the protein encoded by this cDNA shows
      some similarity to sequences of other terpene synthases. The expression of the
      GES cDNA in Escherichia coli resulted in a protein with enzymatic activity
      essentially identical to that of plant-purified GES. RNA gel-blot analysis
      indicated that GES is expressed in glands but not in leaves of basil cv Sweet
      Dani, whose glands contain geraniol and citral, and not in glands or leaves of
      another basil variety that makes other monoterpenes but not geraniol or citral.

PMID- 14657410
TI  - A methyl viologen-resistant mutant of Arabidopsis, which is allelic to ozone
      sensitive rcd1, is tolerant to supplemental ultraviolet-B irradiation.
AB  - To better understand the role of active oxygen species (AOS) in acquired
      resistance to increased levels of ultraviolet (UV)-B irradiation in plants, we
      isolated an Arabidopsis mutant that is resistant to methyl viologen, and its
      sensitivity to UV-B was investigated. A complementation test revealed that the
      obtained mutant was allelic to the ozone-sensitive radical-induced cell death1-1
      (rcd1-1). Therefore, this mutant was named rcd1-2. rcd1-2 was recessive and
      nearly 4-fold more resistant to methyl viologen than wild type. It exhibited a
      higher tolerance to short-term UV-B supplementation treatments than the wild
      type: UV-B-induced formation of cyclobutane pyrimidine dimers was reduced by one
      half after 24 h of exposure; the decrease in quantum yield of photosystem II was
      also diminished by 40% after 12 h of treatment. Furthermore, rcd1-2 was tolerant
      to freezing. Steady-state mRNA levels of plastidic Cu/Zn superoxide dismutase and
      stromal ascorbate peroxidase were higher in rcd1-2 than in wild type, and the
      mRNA level of the latter enzyme was enhanced by UV-B exposure more effectively in
      rcd1-2. UV-B-absorbing compounds were more accumulated in rcd1-2 than in wild
      type after UV-B exposure for 24 h. These findings suggest that rcd1-2 methyl
      viologen resistance is due to the enhanced activities of the AOS-scavenging
      enzymes in chloroplasts and that the acquired tolerance to the short-term UV-B
      exposure results from a higher accumulation of sunscreen pigments. rcd1 appears
      to be a mutant that constitutively shows stress responses, leading to
      accumulation of more pigments and AOS-scavenging enzymes without any stresses.

PMID- 14657411
TI  - INS VNTR is a QTL for the insulin response to oral glucose in obese children.
AB  - We performed a genotype-phenotype association study to examine whether the
      insulin VNTR (INS VNTR) polymorphism located in the insulin gene promoter was
      associated with changes in insulin response to oral glucose. Two classes of INS
      VNTR alleles are observed in Caucasians, the "short" class I and the "long" class
      III. Plasma insulin and glucose concentrations and indices of insulin secretion
      (IGI) and sensitivity (ISI) were measured using an oral glucose tolerance test
      (OGTT) in 387 obese children aged 12 +/- 0.1 yr with a mean body mass index (BMI)
      of 30.6 kg/m(2) (161% of the normal mean). During OGTT, plasma insulin and IGI
      were 20-30% higher in I/I obese children vs. III carriers (P < 0.01). A general
      linear model adjusting for age, sex, and puberty was also used to evaluate the
      influence of the VNTR genotype on the BMI-IGI (P = 0.07) and the BMI-ISI (P <
      0.006) relationships. The INS VNTR can therefore be considered a quantitative
      trait locus influencing glucose-stimulated insulin physiology in obese juveniles.

PMID- 14657413
TI  - International Union of Pharmacology. XXXIX. Compendium of voltage-gated ion
      channels: sodium channels.
AB  - This summary article presents an overview of the molecular relationships among
      the voltage-gated sodium channels and a standard nomenclature for them, which is
      derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete
      Compendium, including data tables for each member of the sodium channel family
      can be found at <http://www.iuphar-db.org/iuphar-ic/>.

PMID- 14657414
TI  - International Union of Pharmacology. XL. Compendium of voltage-gated ion
      channels: calcium channels.
AB  - This summary article presents an overview of the molecular relationships among
      the voltage-gated calcium channels and a standard nomenclature for them, which is
      derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete
      Compendium, including data tables for each member of the calcium channel family
      can be found at http://www.iuphar-db.org/iuphar-ic/.

PMID- 14657415
TI  - International Union of Pharmacology. XLI. Compendium of voltage-gated ion
      channels: potassium channels.
AB  - This summary article presents an overview of the molecular relationships among
      the voltage-gated potassium channels and a standard nomenclature for them, which
      is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete
      Compendium, including data tables for each member of the potassium channel family
      can be found at http://www.iuphar-db.org/iuphar-ic/.

PMID- 14657416
TI  - International Union of Pharmacology. XLII. Compendium of voltage-gated ion
      channels: cyclic nucleotide-modulated channels.
AB  - This summary article presents an overview of the molecular relationships among
      the voltage-gated cyclic nucleotide-modulated channels and a standard
      nomenclature for them, which is derived from the IUPHAR Compendium of Voltage
      Gated Ion Channels. The complete Compendium, including data tables for each
      member of the cyclic nucleotide-modulated channel family can be found at
      http://www.iuphar-db.org/iuphar-ic/.

PMID- 14657417
TI  - International Union of Pharmacology. XLIII. Compendium of voltage-gated ion
      channels: transient receptor potential channels.
AB  - The transient receptor potential (TRP) proteins are six transmembrane-containing
      subunits that combine to form cation-selective ion channels. TRP channels are
      present in yeast, Drosophila, Caenorhabditis elegans, and mammals. They are
      widely distributed and sense local changes in stimuli ranging from light to
      temperature and osmolarity. Mammals contain at least 22 distinct genes encoding
      these ion channels. This summary article presents an overview of the molecular
      relationships among the TRP channels and a standard nomenclature for them, which
      is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete
      Compendium, including data tables for each member of the TRP channel family, can
      be found at http://www.iuphar-db.org/iuphar-ic/.

PMID- 14657418
TI  - International Union of Pharmacology Committee on Receptor Nomenclature and Drug
      Classification. XXXVIII. Update on terms and symbols in quantitative
      pharmacology.
AB  - The recommendations that follow have been updated from the proposals of a
      Technical Subcommittee set up by the International Union of Pharmacology
      Committee on Receptor Nomenclature and Drug Classification (Jenkinson DH, Barnard
      EA, Hoyer D, Humphrey PPA, Leff P, and Shankley NP (1995) International Union of
      Pharmacology Committee on Receptor Nomenclature and Drug Classification. IX.
      Recommendations on terms and symbols in quantitative pharmacology. Pharmacol Rev
      47:255-266).

PMID- 14657419
TI  - G protein modulation of voltage-gated calcium channels.
AB  - Calcium influx into any cell requires fine tuning to guarantee the correct
      balance between activation of calcium-dependent processes, such as muscle
      contraction and neurotransmitter release, and calcium-induced cell damage. G
      protein-coupled receptors play a critical role in negative feedback to modulate
      the activity of the CaV2 subfamily of the voltage-dependent calcium channels,
      which are largely situated on neuronal and neuro-endocrine cells. The basis for
      the specificity of the relationships among membrane receptors, G proteins, and
      effector calcium channels will be discussed, as well as the mechanism by which G
      protein-mediated inhibition is thought to occur. The inhibition requires free G
      beta gamma dimers, and the cytoplasmic linker between domains I and II of the
      CaV2 alpha 1 subunits binds G beta gamma dimers, whereas the intracellular N
      terminus of CaV2 alpha 1 subunits provides essential determinants for G protein
      modulation. Evidence suggests a key role for the beta subunits of calcium
      channels in the process of G protein modulation, and the role of a class of
      proteins termed "regulators of G protein signaling" will also be described.

PMID- 14657420
TI  - RNA interference in biology and medicine.
AB  - First discovered in plants the nematode Caenorhabditis elegans, the production of
      small interfering RNAs (siRNAs) that bind to and induce the degradation of
      specific endogenous mRNAs is now recognized as a mechanism that is widely
      employed by eukaryotic cells to inhibit protein production at a post
      transcriptional level. The endogenous siRNAs are typically 19- to 23-base double
      stranded RNA oligonucleotides, produced from much larger RNAs that upon binding
      to target mRNAs recruit RNases to a protein complex that degrades the targeted
      mRNA. Methods for expressing siRNAs in cells in culture and in vivo using viral
      vectors, and for transfecting cells with synthetic siRNAs, have been developed
      and are being used to establish the functions of specific proteins in various
      cell types and organisms. RNA interference methods provide several major
      advantages over prior methods (antisense DNA or antibody-based techniques) for
      suppressing gene expression. Recent preclinical studies suggest that RNA
      interference technology holds promise for the treatment of various diseases.
      Pharmacologists have long dreamed of the ability to selectively antagonize or
      eliminate the function of individual proteins--RNAi technology may eventually
      make that dream a reality.

PMID- 14657421
TI  - Induction of drug metabolism: the role of nuclear receptors.
AB  - Induction of drug metabolism was described more than 40 years ago. Progress in
      understanding the molecular mechanism of induction of drug-metabolizing enzymes
      was made recently when the important roles of the pregnane X receptor (PXR) and
      the constitutive androstane receptor (CAR), two members of the nuclear receptor
      superfamily of transcription factors, were discovered to act as sensors for
      lipophilic xenobiotics, including drugs. CAR and PXR bind as heterodimeric
      complexes with the retinoid X receptor to response elements in the regulatory
      regions of the induced genes. PXR is directly activated by xenobiotic ligands,
      whereas CAR is involved in a more complex and less well understood mechanism of
      signal transduction triggered by drugs. Most recently, analysis of these
      xenobiotic-sensing nuclear receptors and their nonmammalian precursors such as
      the chicken xenobiotic receptor suggests an important role of PXR and CAR also in
      endogenous pathways, such as cholesterol and bile acid biosynthesis and
      metabolism. In this review, recent findings regarding xenosensors and their
      target genes are summarized and are put into an evolutionary perspective in
      regard to how a living organism has derived a system that is able to deal with
      potentially toxic compounds it has not encountered before.

PMID- 14657422
TI  - A protective gene for graft-versus-host disease.

PMID- 14657423
TI  - Insulin-like growth factors and the basis of growth.

PMID- 14657424
TI  - Incentive-based formularies.

PMID- 14657425
TI  - Rx: Canadian drugs.

PMID- 14657426
TI  - Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in
      asymptomatic adults.
AB  - BACKGROUND: We evaluated the performance characteristics of computed tomographic
      (CT) virtual colonoscopy for the detection of colorectal neoplasia in an average
      risk screening population. METHODS: A total of 1233 asymptomatic adults (mean
      age, 57.8 years) underwent same-day virtual and optical colonoscopy. Radiologists
      used the three-dimensional endoluminal display for the initial detection of
      polyps on CT virtual colonoscopy. For the initial examination of each colonic
      segment, the colonoscopists were unaware of the findings on virtual colonoscopy,
      which were revealed to them before any subsequent reexamination. The sensitivity
      and specificity of virtual colonoscopy and the sensitivity of optical colonoscopy
      were calculated with the use of the findings of the final, unblinded optical
      colonoscopy as the reference standard. RESULTS: The sensitivity of virtual
      colonoscopy for adenomatous polyps was 93.8 percent for polyps at least 10 mm in
      diameter, 93.9 percent for polyps at least 8 mm in diameter, and 88.7 percent for
      polyps at least 6 mm in diameter. The sensitivity of optical colonoscopy for
      adenomatous polyps was 87.5 percent, 91.5 percent, and 92.3 percent for the three
      sizes of polyps, respectively. The specificity of virtual colonoscopy for
      adenomatous polyps was 96.0 percent for polyps at least 10 mm in diameter, 92.2
      percent for polyps at least 8 mm in diameter, and 79.6 percent for polyps at
      least 6 mm in diameter. Two polyps were malignant; both were detected on virtual
      colonoscopy, and one of them was missed on optical colonoscopy before the results
      on virtual colonoscopy were revealed. CONCLUSIONS: CT virtual colonoscopy with
      the use of a three-dimensional approach is an accurate screening method for the
      detection of colorectal neoplasia in asymptomatic average-risk adults and
      compares favorably with optical colonoscopy in terms of the detection of
      clinically relevant lesions.

PMID- 14657427
TI  - Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease
      and survival after hematopoietic-cell transplantation.
AB  - BACKGROUND: Polymorphisms in cytokine genes can influence immune responses,
      inflammation, and tissue injury and may affect the outcome of hematopoietic stem
      cell transplantation. METHODS: We analyzed single-nucleotide polymorphisms in the
      genes for interleukin-1beta, interleukin-1-receptor antagonist, interleukin-6,
      interleukin-10 (IL10), and tumor necrosis factor alpha in 570 transplant
      recipients and their HLA-identical sibling donors. Genotypes were tested for an
      association with graft-versus-host disease (GVHD) by multivariable analysis. A
      second cohort of 423 transplant recipients was independently analyzed for the
      genotype associations identified in the first cohort. RESULTS: The recipient's
      IL10 promoter region genotype was significantly associated with the risk of acute
      GVHD in the first cohort. Analysis of all 993 transplant recipients showed that,
      as compared with the C/C genotype, the IL10 -592A/A genotype was associated with
      a decreased risk of grade III or IV acute GVHD (hazard ratio, 0.4; 95 percent
      confidence interval, 0.2 to 0.9; P=0.02) and death in remission (hazard ratio,
      0.6; 95 percent confidence interval, 0.3 to 1.0; P=0.05). A haplotype analysis
      showed that the IL10 -592A allele was a specific marker for a promoter haplotype,
      T-C-A-T-A, defined by five polymorphisms at positions -3575, -2763, -1082, -819,
      and -592, respectively. CONCLUSIONS: Among recipients of hematopoietic cells from
      an HLA-identical sibling, the IL10 -592A allele is a marker of a favorable
      outcome after transplantation.

PMID- 14657428
TI  - IGF-I receptor mutations resulting in intrauterine and postnatal growth
      retardation.
AB  - BACKGROUND: Approximately 10 percent of infants with intrauterine growth
      retardation remain small, and the causes of their growth deficits are often
      unclear. We postulated that mutations in the gene for the insulin-like growth
      factor I receptor (IGF-IR) might underlie some cases of prenatal and postnatal
      growth failure. METHODS: We screened two groups of children for abnormalities in
      the IGF-IR gene. In one group of 42 patients with unexplained intrauterine growth
      retardation and subsequent short stature, we used single-strand conformation
      polymorphism analysis, followed by direct DNA sequencing of any abnormalities
      found. A second cohort consisted of 50 children with short stature who had
      elevated circulating IGF-I concentrations. Complete sequencing of the IGF-IR gene
      was performed with DNA from nine children. We also studied a control group of 43
      children with normal birth weights. RESULTS: In the first cohort, we identified
      one girl who was a compound heterozygote for point mutations in exon 2 of the IGF
      IR gene that altered the amino acid sequence to Arg108Gln in one allele and
      Lys115Asn in the other. Fibroblasts cultured from the patient had decreased IGF-I
      receptor function, as compared with that in control fibroblasts. No such
      mutations were found in the 43 controls. In the second group, we identified one
      boy with a nonsense mutation (Arg59stop) that reduced the number of IGF-I
      receptors on fibroblasts. Both children had intrauterine growth retardation and
      poor postnatal growth. CONCLUSIONS: Mutations in the IGF-IR gene that lead to
      abnormalities in the function or number of IGF-I receptors may also retard
      intrauterine and subsequent growth in humans.

PMID- 14657429
TI  - Images in clinical medicine. Oral lichen planus as a clinical sign of graft
      versus-host disease.

PMID- 14657430
TI  - The effect of incentive-based formularies on prescription-drug utilization and
      spending.
AB  - BACKGROUND: Many employers and health plans have adopted incentive-based
      formularies in an attempt to control prescription-drug costs. METHODS: We used
      claims data to compare the utilization of and spending on drugs in two employer
      sponsored health plans that implemented changes in formulary administration with
      those in comparison groups of enrollees covered by the same insurers. One plan
      simultaneously switched from a one-tier to a three-tier formulary and increased
      all enrollee copayments for medications. The second switched from a two-tier to a
      three-tier formulary, changing only the copayments for tier-3 drugs. We examined
      the utilization of angiotensin-converting-enzyme (ACE) inhibitors, proton-pump
      inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins). RESULTS: Enrollees covered by the employer that implemented more
      dramatic changes experienced slower growth than the comparison group in the
      probability of the use of a drug and a major shift in spending from the plan to
      the enrollee. Among the enrollees who were initially taking tier-3 statins, more
      enrollees in the intervention group than in the comparison group switched to tier
      1 or tier-2 medications (49 percent vs. 17 percent, P<0.001) or stopped taking
      statins entirely (21 percent vs. 11 percent, P=0.04). Patterns were similar for
      ACE inhibitors and proton-pump inhibitors. The enrollees covered by the employer
      that implemented more moderate changes were more likely than the comparison
      enrollees to switch to tier-1 or tier-2 medications but not to stop taking a
      given class of medications altogether. CONCLUSIONS: Different changes in
      formulary administration may have dramatically different effects on utilization
      and spending and may in some instances lead enrollees to discontinue therapy. The
      associated changes in copayments can substantially alter out-of-pocket spending
      by enrollees, the continuation of the use of medications, and possibly the
      quality of care.

PMID- 14657431
TI  - Clinical practice. Dysplastic nevi.

PMID- 14657432
TI  - Esophageal cancer.

PMID- 14657433
TI  - Clinical problem-solving. Step by step.

PMID- 14657434
TI  - Grants, politics, and the NIH.

PMID- 14657435
TI  - Screening virtual colonoscopy--ready for prime time?

PMID- 14657436
TI  - Forestalling fibrosis.

PMID- 14657437
TI  - High-dose dexamethasone as initial treatment for immune thrombocytopenic purpura.

PMID- 14657438
TI  - Structured treatment interruption for patients with human immunodeficiency virus
      infection.

PMID- 14657439
TI  - Antimyelin antibodies in multiple sclerosis.

PMID- 14657440
TI  - Molecular heterogeneity in acute renal allograft rejection and DNA microarrays.

PMID- 14657441
TI  - Everolimus in cardiac-transplant recipients.

PMID- 14657442
TI  - Chemotherapy for bladder cancer.

PMID- 14657443
TI  - Lost in translation.

PMID- 14657444
TI  - Transient memory impairment and hallucinations associated with tolterodine use.

PMID- 14657445
TI  - Images in clinical medicine. Choroidal metastasis from renal-cell carcinoma.

PMID- 14657446
TI  - Predicting major neurological improvement with intravenous recombinant tissue
      plasminogen activator treatment of stroke.
AB  - BACKGROUND AND PURPOSE: In the National Institute of Neurological Disorders and
      Stroke (NINDS) rt-PA Stroke Study, major neurological improvement within 24 hours
      (MNI) occurred significantly more frequently with recombinant tissue plasminogen
      activator (rtPA) treatment than with placebo. We explored the relationship
      between MNI and 3-month favorable outcome and sought clinical predictors of MNI.
      METHODS: Data from 312 rtPA-treated patients from the NINDS trial were used to
      assess the ability of MNI to predict favorable outcome at 3 months as defined by
      a modified Rankin Scale score of 0 to 1. Next, a multivariable predictive model
      was developed for MNI within the same data set. Clinical variables examined
      included age, time to treatment (TTT), diabetes, pretreatment glucose, baseline
      National Institutes of Health Stroke Scale score, pretreatment blood pressure,
      history of atrial fibrillation, weight >100 kg, and a dense artery sign. Finally,
      this model was used to forecast into the placebo group of the NINDS trial to
      assess the uniqueness of the predictors in the rtPA-treated group. RESULTS: MNI
      had a positive predictive value and negative predictive value of 0.70 for
      predicting favorable 3-month outcome. Only age [odds ratio (OR), 0.68; 95%
      confidence interval (CI), 0.47 to 0.99] and TTT (OR, 0.56; 95% CI, 0.34 to 0.91)
      appear to be independently associated with MNI. The model performed only
      moderately well (area under the receiver-operating characteristic curve, 0.66).
      Age (OR, 0.67; 95% CI, 0.45 to 0.99) but not TTT was associated with MNI in the
      placebo group. CONCLUSIONS: MNI may be a useful surrogate for thrombolytic
      activity and is predictive of favorable 3-month outcome. When rates of MNI in
      different populations of stroke patients treated with thrombolysis are compared,
      adjustments for age and TTT may be necessary.

PMID- 14657447
TI  - Effects of semantic treatment on verbal communication and linguistic processing
      in aphasia after stroke: a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Semantic deficits, deficits in word meaning, have a large
      impact on aphasic patients' verbal communication. We investigated the effects of
      semantic treatment on verbal communication in a randomized controlled trial.
      METHODS: Fifty-eight patients with a combined semantic and phonological deficit
      were randomized to receive either semantic treatment or the control treatment
      focused on word sound (phonology). Fifty-five patients completed pretreatment and
      posttreatment assessment of verbal communication (Amsterdam Nijmegen Everyday
      Language Test [ANELT]). In an on-treatment analysis (n=46), treatment-specific
      effects on semantic and phonological measures were explored. RESULTS: Both groups
      improved on the ANELT, with no difference between groups in overall score
      (difference, -1.1; 95% confidence interval [CI], -5.3 to 3.1). After semantic
      treatment, patients improved on a semantic measure (mean improvement, 2.9; 95%
      CI, 1.2 to 4.6), whereas after phonological treatment, patients improved on
      phonological measures (mean improvement, 3.0; 95% CI, 1.4 to 4.7, and 3.0; 95%
      CI, 1.2 to 4.7). CONCLUSIONS: No differences in primary outcome were noted
      between the 2 treatments. Our findings challenge the current notion that semantic
      treatment is more effective than phonological treatment for patients with a
      combined semantic and phonological deficit. The selective gains on the semantic
      and phonological measures suggest that improved verbal communication was achieved
      in a different way for each treatment group.

PMID- 14657448
TI  - Low serum magnesium predicts neurological events in patients with advanced
      atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Magnesium (Mg) deficiency is thought to be a risk factor
      for cerebrovascular atherosclerosis and complications. We investigated the
      prognostic impact of Mg serum levels with respect to the occurrence of
      neurological events in patients with advanced atherosclerosis. METHODS: We
      prospectively studied 323 patients with symptomatic peripheral artery disease and
      intermittent claudication (197 men; median age, 68 years). Serum Mg was
      determined, and patients were followed for a median of 20 months (interquartile
      range, 12 to 25 months) for the occurrence of neurological events, defined as
      ischemic stroke and/or carotid revascularization (carotid endarterectomy or
      carotid stenting). Multivariate Cox proportional hazards analysis was applied to
      assess the association of serum Mg (in tertiles) and neurological events.
      RESULTS: Neurological events occurred in 35 patients (11%) (15 patients with
      stroke, 13 with carotid revascularization, and 7 with stroke and subsequent
      revascularization). Compared with patients in the highest tertile of Mg serum
      levels (>0.84 mmol/L), patients with Mg serum values <0.76 mmol/L (lowest
      tertile) exhibited a 3.29-fold increased adjusted risk (95% CI, 1.34 to 7.90;
      P=0.009) for neurological events, but patients with Mg serum values of 0.76
      mmol/L to 0.84 mmol/L (middle tertile) had no increased risk (adjusted hazard
      ratio, 1.10; 95% CI, 0.35 to 3.33; P=0.88). Mg serum levels were not associated
      with all-cause mortality (P=0.87) or coronary events (P=0.67) during follow-up.
      CONCLUSIONS: Low Mg serum levels indicate an increased risk for neurological
      events in patients with symptomatic peripheral artery disease, favoring Mg
      substitution therapy in those patients with advanced atherosclerosis.

PMID- 14657449
TI  - Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a
      community-based population of middle-aged adults: the Atherosclerosis Risk in
      Communities (ARIC) study.
AB  - BACKGROUND AND PURPOSE: Although the risks associated with heavy drinking for
      increased stroke and neurodegenerative changes are well established, the effects
      on the brain of low to moderate alcohol intake are unclear. Subclinical cerebral
      abnormalities identified on MRI have been associated with neurocognitive decline
      and incident stroke. We examined the associations of alcohol intake with MRI
      defined cerebral abnormalities in a middle-aged, population-based cohort.
      METHODS: During 1993-1994, a total of 1909 middle-aged adults (40% men and 49%
      blacks) from 2 communities in the Atherosclerosis Risk in Communities (ARIC)
      Study (Forsyth County, North Carolina, and Jackson, Miss) underwent a cerebral
      MRI examination. Trained neuroradiologists coded the images for the presence of
      infarction and the extent (10-point scale) of white matter lesions, ventricular
      size, and sulcal size. RESULTS: In logistic regression analyses, there was no
      association between alcohol intake and the presence of MRI infarction. In linear
      regression analyses, alcohol intake was not associated with white matter grade.
      However, intake of each additional alcoholic drink per week was associated with a
      0.01 grade greater ventricular size (P=0.03) and a 0.009 grade greater sulcal
      size (P=0.02) after adjustment for age, sex, race, body mass index, smoking,
      income, sports index, and diabetes. The positive associations of alcohol intake
      with ventricular and sulcal size were consistent across sex and race subgroups.
      CONCLUSIONS: A protective effect of low to moderate alcohol intake on cerebral
      infarction was not found; moreover, increased alcohol intake was associated with
      brain atrophy.

PMID- 14657450
TI  - Parity and risk of subarachnoid hemorrhage in women: a nested case-control study
      based on national Swedish registries.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is the only type of stroke
      with female predominance, suggesting that reproductive factors may play a role in
      the etiology. We conducted a population-based study to examine the influence of
      parity on the risk of SAH in women. METHODS: We linked data from 3 national
      Swedish registries to identify first-ever hospitalizations for SAH in a cohort of
      women followed up since first childbirth during 1973-1997. Within this cohort, we
      conducted a nested case-control study and estimated the odds ratio (OR) and 95%
      CI of SAH by parity adjusted for age, calendar period, and length of follow-up.
      Information on smoking habits before the subject's first childbirth was available
      in a subset of the data (women with first childbirths during 1982-1997). RESULTS:
      Of the 887 cases identified, 70% had suffered from SAH > or =5 years after giving
      birth to their last child. The OR declined with increasing parity (1 child:
      reference; 2: OR=0.83 [95% CI, 0.70 to 0.99]; 3: OR=0.72 [95% CI, 0.58 to 0.91];
      4: OR=0.72 [95% CI, 0.48 to 1.08]; > or =5: OR=0.67 [95% CI, 0.32 to 1.41]).
      Adjusting for daily cigarette consumption before first childbirth in the
      subsample in which this information was available reduced but did not eliminate
      the association of the disorder with parity. CONCLUSIONS: Parity may confer a
      moderate long-term protective effect on the risk of SAH. The biological mechanism
      underlying this association is currently unknown.

PMID- 14657451
TI  - Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical
      Emboli from Large Veins in Ischemic Stroke (PELVIS) study.
AB  - BACKGROUND AND PURPOSE: Cryptogenic stroke is associated with an increased
      prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in
      Ischemic Stroke (PELVIS) study hypothesized that patients with cryptogenic stroke
      have an increased prevalence of pelvic deep venous thrombosis (DVT). METHODS: At
      5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the
      pelvis within 72 hours of new symptom onset. Clinical data were then determined.
      Radiologists blinded to clinical data later read the scans. RESULTS: The 95
      patients who met entry criteria were scanned. Their mean+/-SD age was 46+/-10
      years, and time from stroke onset to pelvic MRV scan was 49+/-16 hours. Compared
      with those with stroke of determined origin (n=49), patients with cryptogenic
      stroke (n=46) were significantly younger, had a higher prevalence of patent
      foramen ovale (61% versus 19%), and had less atherosclerosis risk factors.
      Cryptogenic patients had more MRV scans with a high probability for pelvic DVT
      (20%) than patients with stroke of determined origin (4%, P<0.03), with most
      having an appearance of a chronic DVT. CONCLUSIONS: In this study of young stroke
      patients evaluated early after stroke, patients with cryptogenic stroke showed
      differences in several clinical features compared with patients with stroke of
      determined origin, including increased prevalence of pelvic DVT. The results
      require confirmation but suggest that paradoxical embolus from the pelvic veins
      may be the cause of stroke in a subset of patients classified as having
      cryptogenic stroke.

PMID- 14657452
TI  - Acute ischemic stroke in hospitalized medicare patients: evaluation and
      treatment.
AB  - BACKGROUND AND PURPOSE: This study describes several quality indicators of care
      in hospitalized stroke patients in Michigan from 1998 to 1999. SUMMARY OF REPORT:
      Median times from admission to head CT/MRI (89.5 minutes) and thrombolysis (113
      minutes) exceeded recommended guidelines. Deep venous thrombosis prophylaxis was
      used in only 13.8% of eligible patients. CONCLUSIONS: Timing for brain imaging
      and acute ischemic stroke symptom onset need to be better documented, along with
      more provider education for routine deep venous thrombosis prophylaxis.

PMID- 14657453
TI  - Inhibition of intercellular adhesion molecule-1 protein expression by antisense
      oligonucleotides is neuroprotective after transient middle cerebral artery
      occlusion in rat.
AB  - BACKGROUND AND PURPOSE: The present study was performed to determine whether
      antisense inhibition of intercellular adhesion molecule-1 (ICAM-1) protein
      expression decreases focal ischemic brain damage. METHODS: Male spontaneously
      hypertensive rats underwent 1-hour middle cerebral artery occlusion (MCAO) and 24
      hour reperfusion. Rats were infused with ICAM-1 antisense or control
      oligodeoxynucleotides (ODNs) (48 nmol/d ICV) or vehicle, starting 24 hours before
      MCAO and continuing until the time of death. ICAM-1 and vascular cell adhesion
      molecule-1 (VCAM-1) mRNA levels were measured by real-time polymerase chain
      reaction. ICAM-1 protein knockdown was confirmed by Western blotting. Infarct
      volume was quantified by the use of cresyl violet-stained brain sections.
      Neurological deficits were evaluated. Mean arterial blood pressure was recorded
      by laser Doppler. Tissue penetration of antisense was confirmed by the use of
      fluorescent ODNs. RESULTS: Transient MCAO upregulated ICAM-1, but not VCAM-1,
      mRNA expression in the ipsilateral cortex between 3 and 72 hours of reperfusion.
      ICAM-1 antisense infusion prevented ischemia-induced ICAM-1 protein expression
      and reduced total infarct volume (by 53%; P<0.05; 226+/-35 mm3 in control ODN
      group and 104+/-27 mm3 in antisense ODN group; n=8 each) and mean neurological
      deficit score (by 44%; P<0.05; 2.4 in control ODN group and 1.3 in antisense ODN
      group; n=8 each). Neither control nor antisense ODN had any effect on mean
      arterial blood pressure and the physiological parameters monitored during MCAO.
      Compared with noninfused control, intracerebroventricular infusion of artificial
      cerebrospinal fluid or antisense or sense ODN had no significant effect on the
      regional cerebral blood flow changes that accompanied ischemia and reperfusion.
      CONCLUSIONS: Increased ICAM-1 expression is implicated in the pathogenesis of
      focal ischemia since ICAM-1 protein knockdown decreased ischemic brain damage.
      The mechanism by which ICAM-1 inhibition offers neuroprotection is independent of
      blood pressure modulation.

PMID- 14657454
TI  - Inflammation, homocysteine, and vitamin B6 status after ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Epidemiological studies have described an association
      between low vitamin B6 (measured as pyridoxal 5'-phosphate [PLP]) and ischemic
      stroke, independent of homocysteine (tHcy). We investigated B6 status, tHcy, and
      inflammation (measured by C-reactive protein [CRP]) in patients with stroke and
      controls. METHODS: Consecutive cases with new ischemic stroke were compared with
      matched controls. Fasting tHcy, PLP, and CRP were measured. RESULTS: The adjusted
      odds ratio of low PLP in the highest compared with the lowest CRP quartile was
      16.6 (2, 139.9, P=0.01). Age, CRP, supplemental vitamin use, and albumin were
      independent predictors of PLP (P<0.05 for all). No relationship was observed
      between CRP and tHcy. CONCLUSIONS: The relationship between inflammation and low
      B6 status may partially explain the findings of previous epidemiological studies.

PMID- 14657455
TI  - Predictive value of inflammatory and hemostatic parameters, atherosclerotic risk
      factors, and chest x-ray for aortic arch atheromatosis.
AB  - BACKGROUND AND PURPOSE: Aortic arch atheromatosis (AAA) is a common cause of
      cerebral embolism. Transesophageal echocardiography (TEE) shows not only the
      extension of atherosclerotic plaques but also the mobility of superimposed
      thrombi. In most cases AAA is only detected after the embolic event. This study
      was therefore designed to identify predictive factors for AAA. METHODS: One
      hundred seven consecutive patients referred for routine TEE were included in the
      study. Patients on warfarin therapy, with a history of recent surgery, or with
      any signs of infectious, immunological, or malignant diseases were excluded.
      RESULTS: Diabetes mellitus carried the highest risk for AAA (odds ratio, 3.0),
      followed by hyperlipidemia (2.5) and arterial hypertension (2.3). Age >70 years
      was accompanied with a 1.8-fold increased risk. Patients with aortic
      calcifications on standard chest x-ray had a 4.6-fold higher prevalence. Severe
      AAA was associated with higher levels of C-reactive protein (14.6+/-14.1 versus
      4.9+/-7.2 mg/L), fibrinogen (4.20+/-1.22 versus 3.45+/-1.29 mg/L),
      plasmin/antiplasmin complexes (728+/-297 versus 453+/-243 microg/L), and D-dimers
      (980+/-652 versus 444+/-349 microg/L). CONCLUSIONS: AAA is accompanied by
      elevation of inflammatory and hemostatic parameters. Patients with classic
      cardiovascular risk factors and aortic calcifications on chest x-ray have a
      higher prevalence. Further prospective studies are now warranted to establish a
      risk score to identify patients in whom TEE screening should be undertaken.

PMID- 14657456
TI  - Carotid angioplasty and stenting with and without cerebral protection: clinical
      alert from the Endarterectomy Versus Angioplasty in Patients With Symptomatic
      Severe Carotid Stenosis (EVA-3S) trial.
AB  - BACKGROUND AND PURPOSE: Whether cerebral protection during carotid angioplasty
      and stenting (CAS) is associated with a lower risk of periprocedural stroke or
      death remains to be established. We report on 80 patients randomized in the CAS
      arm of the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe
      Carotid Stenosis trial comparing CAS (with or without cerebral protection) with
      carotid surgery in patients with recently symptomatic, severe carotid stenosis.
      SUMMARY OF REPORT: The Safety Committee recommended stopping unprotected CAS,
      because the 30-day rate of stroke was 3.9 (0.9 to 16.7) times higher than that of
      CAS with cerebral protection (4/15 versus 5/58). CONCLUSIONS: Although this
      result was not based on a randomized comparison of unprotected versus protected
      CAS, it suggests that the use of cerebral protection devices during CAS reduces
      periprocedural strokes.

PMID- 14657457
TI  - Risk factors for first-ever stroke in older people in the north East of England:
      a population-based study.
AB  - BACKGROUND AND PURPOSE: Although older people potentially have most to gain from
      prevention, they have been excluded from or underrepresented in many stroke
      incidence studies. We sought to determine the risk factors for stroke in older
      people. METHODS: A 5-year follow-up study of a population-based cohort of 4440
      subjects aged >65 years in northern England. Subjects were recruited from 27
      general practices between 1995 and 1997. RESULTS: A total of 329 out of 4351
      subjects with follow-up data suffered a first-ever stroke. On multivariate
      analysis, risk factors for stroke in older people included atrial fibrillation
      (hazard ratio [HR], 2.03 [95%CI, 1.31 to 3.16]); previous transient ischemic
      attack (1.87 [95% CI, 1.27 to 2.76]); smoking (1.72 [95% CI,1.28 to 2.32]); and
      cardiovascular disease (1.55 [95% CI, 1.19 to 2.03]). The HR per 10-mm Hg
      increase in systolic blood pressure was 1.15 (95% CI, 1.06 to 1.24). Age was
      associated with a HR of 1.74 (95% CI, 1.42 to 2.12) per 10-year increase.
      CONCLUSIONS: "Classic risk factors" increase the risk of stroke in older people.
      Stroke is not an inevitable consequence of aging, so by identifying and modifying
      risk factors in older people there are opportunities to reduce the incidence and
      mortality of this devastating condition.

PMID- 14657458
TI  - Editorial comment--parity and risk of subarachnoid hemorrhage: an emerging
      association.

PMID- 14657459
TI  - Miniature transmitter release: accident of nature or careful design?
AB  - Miniature transmitter release results from the constitutive low-level release of
      individual vesicles of neurotransmitter. Since the 1950s, this form of synaptic
      transmission has largely been thought to reflect a leaky evoked-release
      mechanism, and it was not clear whether it had a function of its own. Recent data
      challenge this view and suggest that miniature release can affect both the local
      chemistry of synapses and the network properties of neurons.

PMID- 14657460
TI  - Forensic science: oxymoron?

PMID- 14657461
TI  - U.S. science funding. Research catches a break in catch-all spending bill.

PMID- 14657462
TI  - Bioterror trial. Butler cleared on most biosecurity charges, convicted of fraud.

PMID- 14657463
TI  - AIDS research. Earmark draws criticism, creates confusion.

PMID- 14657464
TI  - ITER. E.U. puts France in play for fusion sweepstakes.

PMID- 14657466
TI  - Mantle dynamics. Mantle plumes both tall and short?

PMID- 14657465
TI  - Space-based astronomy. NASA draws the line at servicing Hubble.

PMID- 14657467
TI  - Nonproliferation. Radioactive sources move from a concern to a crisis.

PMID- 14657468
TI  - Iraq. Researchers look west to model new academy.

PMID- 14657469
TI  - Invertebrate paleontology. Gutsy fossil sets record for staying the course.

PMID- 14657470
TI  - Systems biology. Tracing life's circuitry.

PMID- 14657471
TI  - Theoretical physics. At Canada's Perimeter Institute, 'Waterloo' means 'Shangri
      La'.

PMID- 14657472
TI  - Theoretical physics. Perimeter's threefold way.

PMID- 14657473
TI  - Sultan Bin Mohammed Al-Qassimi profile. Building an academic oasis in the Arabian
      desert.

PMID- 14657474
TI  - Don't forget about viruses.

PMID- 14657475
TI  - Developing world science strategies.

PMID- 14657476
TI  - The parasol effect on climate.

PMID- 14657477
TI  - The European carbon budget: a gap.

PMID- 14657478
TI  - Perceptions of science essay. Privacy and property on the Net: research
      questions.

PMID- 14657479
TI  - Neuroscience. Microglia: the enemy within?

PMID- 14657480
TI  - Cell biology. Smurfing at the leading edge.

PMID- 14657481
TI  - Atmospheric science. How water enters the stratosphere.

PMID- 14657482
TI  - Chemistry. Unraveling the molecular mechanisms of photoacidity.

PMID- 14657483
TI  - Planetary science. Learning to think like Martians.

PMID- 14657484
TI  - Plant sciences. Deciding when to flower.

PMID- 14657485
TI  - The division of endosymbiotic organelles.
AB  - Mitochondria and chloroplasts are essential eukaryotic organelles of
      endosymbiotic origin. Dynamic cellular machineries divide these organelles. The
      mechanisms by which mitochondria and chloroplasts divide were thought to be
      fundamentally different because chloroplasts use proteins derived from the
      ancestral prokaryotic cell division machinery, whereas mitochondria have largely
      evolved a division apparatus that lacks bacterial cell division components.
      Recent findings indicate, however, that both types of organelles universally
      require dynamin-related guanosine triphosphatases to divide. This mechanistic
      link provides fundamental insights into the molecular events driving the
      division, and possibly the evolution, of organelles in eukaryotes.

PMID- 14657486
TI  - Cell migration: integrating signals from front to back.
AB  - Cell migration is a highly integrated multistep process that orchestrates
      embryonic morphogenesis; contributes to tissue repair and regeneration; and
      drives disease progression in cancer, mental retardation, atherosclerosis, and
      arthritis. The migrating cell is highly polarized with complex regulatory
      pathways that spatially and temporally integrate its component processes. This
      review describes the mechanisms underlying the major steps of migration and the
      signaling pathways that regulate them, and outlines recent advances investigating
      the nature of polarity in migrating cells and the pathways that establish it.

PMID- 14657487
TI  - Insulin signaling in health and disease.
AB  - The signaling pathways used by insulin have been identified [M. White, Insulin
      Signaling Pathway, Sci. STKE (Connections Map, as seen November 2003),
      http://stke.sciencemag.org/cgi/cm/cmp_12069]. Now our challenge is to understand
      how the failure of these signals is associated with obesity and the progressive
      failure of pancreatic beta cells that leads to diabetes. Whether better
      management of chronic inflammation can improve insulin action is an important
      area of investigation. Drugs that stimulate IRS2 (insulin receptor substrate
      protein 2) synthesis or signaling might be a good starting point. This knowledge
      will lead to rational strategies that prevent or cure diabetes.

PMID- 14657488
TI  - Global air quality and pollution.
AB  - The impact of global air pollution on climate and the environment is a new focus
      in atmospheric science. Intercontinental transport and hemispheric air pollution
      by ozone jeopardize agricultural and natural ecosystems worldwide and have a
      strong effect on climate. Aerosols, which are spread globally but have a strong
      regional imbalance, change global climate through their direct and indirect
      effects on radiative forcing. In the 1990s, nitrogen oxide emissions from Asia
      surpassed those from North America and Europe and should continue to exceed them
      for decades. International initiatives to mitigate global air pollution require
      participation from both developed and developing countries.

PMID- 14657489
TI  - Modern global climate change.
AB  - Modern climate change is dominated by human influences, which are now large
      enough to exceed the bounds of natural variability. The main source of global
      climate change is human-induced changes in atmospheric composition. These
      perturbations primarily result from emissions associated with energy use, but on
      local and regional scales, urbanization and land use changes are also important.
      Although there has been progress in monitoring and understanding climate change,
      there remain many scientific, technical, and institutional impediments to
      precisely planning for, adapting to, and mitigating the effects of climate
      change. There is still considerable uncertainty about the rates of change that
      can be expected, but it is clear that these changes will be increasingly
      manifested in important and tangible ways, such as changes in extremes of
      temperature and precipitation, decreases in seasonal and perennial snow and ice
      extent, and sea level rise. Anthropogenic climate change is now likely to
      continue for many centuries. We are venturing into the unknown with climate, and
      its associated impacts could be quite disruptive.

PMID- 14657490
TI  - Mutations in RNAi rescue aberrant chemotaxis of ADAR mutants.

PMID- 14657491
TI  - Probing the threshold to H atom transfer along a hydrogen-bonded ammonia wire.
AB  - We characterized the entrance channel, reaction threshold, and mechanism of an
      excited-state H atom transfer reaction along a unidirectionally hydrogen-bonded
      "wire" -O-H...NH3...NH3...NH3...N. Excitation of supersonically cooled 7
      hydroxyquinoline.(NH3)3 to its vibrationless S1 state produces no reaction,
      whereas excitation of ammonia-wire vibrations induces H atom transfer with a
      reaction threshold approximately 200 wave numbers. Further translocation steps
      along the wire produce the S1 state 7-ketoquinoline.(NH3)3 tautomer. Ab initio
      calculations show that proton and electron movement along the wire are closely
      coupled. The rate-controlling S1 state barriers arise from crossings of a pipi*
      with a Rydberg-type pisigma* state.

PMID- 14657492
TI  - Direct detection of the Yarkovsky effect by radar ranging to asteroid 6489
      Golevka.
AB  - Radar ranging from Arecibo, Puerto Rico, to the 0.5-kilometer near-Earth asteroid
      6489 Golevka unambiguously reveals a small nongravitational acceleration caused
      by the anisotropic thermal emission of absorbed sunlight. The magnitude of this
      perturbation, known as the Yarkovsky effect, is a function of the asteroid's mass
      and surface thermal characteristics. Direct detection of the Yarkovsky effect on
      asteroids will help constrain their physical properties, such as bulk density,
      and refine their orbital paths. Based on the strength of the detected
      perturbation, we estimate the bulk density of Golevka to be 2.7(+0.4)(-0.6) grams
      per cubic centimeter.

PMID- 14657493
TI  - Water isotope ratios D/H, 18O/16O, 17O/16O in and out of clouds map dehydration
      pathways.
AB  - Water isotope ratios have been measured by laser absorption spectroscopy in and
      out of cirrus clouds formed in situ and convectively generated in anvils over
      subtropical regions. Water vapor in the tropical and subtropical upper
      troposphere shows a wide range of isotopic depletion not observed previously. The
      range suggests that dehydration of upper tropospheric air occurs both by
      convective dehydration and by gradual dehydration mechanisms. Twenty-five percent
      of upper tropospheric water sampled is in ice particles whose isotopic signatures
      are used to identify those grown in situ from those lofted from below.

PMID- 14657494
TI  - A look inside the San Andreas Fault at Parkfield through vertical seismic
      profiling.
AB  - The San Andreas Fault Observatory at Depth pilot hole is located on the
      southwestern side of the Parkfield San Andreas fault. This observatory includes a
      vertical seismic profiling (VSP) array. VSP seismograms from nearby
      microearthquakes contain signals between the P and S waves. These signals may be
      P and S waves scattered by the local geologic structure. The collected scattering
      points form planar surfaces that we interpret as the San Andreas fault and four
      other secondary faults. The scattering process includes conversions between P and
      S waves, the strengths of which suggest large contrasts in material properties,
      possibly indicating the presence of cracks or fluids.

PMID- 14657495
TI  - An ostracode crustacean with soft parts from the Lower Silurian.
AB  - An exceptionally well-preserved ostracode from the Silurian of Herefordshire,
      United Kingdom, provides a rare view of the fossilized soft-part anatomy of this
      important group of living crustaceans and confirms that Ostracoda were extant in
      the Paleozoic. The fossil has striking similarity to the extant myodocopid family
      Cylindroleberididae, to which it is assigned, and demonstrates remarkable
      evolutionary stasis over 425 million years. The fossil is identified as a male on
      the basis of its copulatory organ.

PMID- 14657496
TI  - Ecological adaptation during incipient speciation revealed by precise gene
      replacement.
AB  - To understand the role of adaptation in speciation, one must characterize the
      ecologically relevant phenotypic effects of naturally occurring alleles at loci
      potentially causing reproductive isolation. The desaturase2 gene of Drosophila
      melanogaster is such a locus. Two geographically differentiated ds2 alleles
      underlie a pheromonal difference between the Zimbabwe and Cosmopolitan races. We
      used a site-directed gene replacement technique to introduce an allele of ds2
      from the Zimbabwe population into Cosmopolitan flies. We show that the
      Cosmopolitan allele confers resistance to cold as well as susceptibility to
      starvation when the entire genetic background is otherwise identical. We conclude
      that ecological adaptation likely accompanies sexual isolation between the two
      behavioral races of D. melanogaster.

PMID- 14657497
TI  - The needle length of bacterial injectisomes is determined by a molecular ruler.
AB  - Size determination represents a fundamental requirement for multicomponent
      biological structures. Some pathogenic bacteria possess a weapon derived from the
      flagellum. Like the flagellum, this type-III secretion apparatus, called the
      injectisome, has a transmembrane basal body, but the external component is a
      needle-like structure instead of a hook and a filament. Here, we provide evidence
      that the length of this needle is determined by the size of a protein, YscP,
      acting as a molecular ruler.

PMID- 14657498
TI  - Spatiotemporal rescue of memory dysfunction in Drosophila.
AB  - We have developed a method for temporal and regional gene expression targeting
      (TARGET) in Drosophila and show the simultaneous spatial and temporal rescue of a
      memory defect. The transient expression of the rutabaga-encoded adenylyl cyclase
      in the mushroom bodies of the adult brain was necessary and sufficient to rescue
      the rutabaga memory deficit, which rules out a developmental brain defect in the
      etiology of this deficit and demonstrates an acute role for rutabaga in memory
      formation in these neurons. The TARGET system offers general utility in
      simultaneously addressing issues of when and where gene products are required.

PMID- 14657499
TI  - Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha
      synuclein.
AB  - Genome-wide screens were performed in yeast to identify genes that enhance the
      toxicity of a mutant huntingtin fragment or of alpha-synuclein. Of 4850 haploid
      mutants containing deletions of nonessential genes, 52 were identified that were
      sensitive to a mutant huntingtin fragment, 86 that were sensitive to alpha
      synuclein, and only one mutant that was sensitive to both. Genes that enhanced
      toxicity of the mutant huntingtin fragment clustered in the functionally related
      cellular processes of response to stress, protein folding, and ubiquitin
      dependent protein catabolism, whereas genes that modified alpha-synuclein
      toxicity clustered in the processes of lipid metabolism and vesicle-mediated
      transport. Genes with human orthologs were overrepresented in our screens,
      suggesting that we may have discovered conserved and nonoverlapping sets of cell
      autonomous genes and pathways that are relevant to Huntington's disease and
      Parkinson's disease.

PMID- 14657500
TI  - Yeast cells provide insight into alpha-synuclein biology and pathobiology.
AB  - Alpha-synuclein is implicated in several neurodegenerative disorders, such as
      Parkinson's disease and multiple system atrophy, yet its functions remain
      obscure. When expressed in yeast, alpha-synuclein associated with the plasma
      membrane in a highly selective manner, before forming cytoplasmic inclusions
      through a concentration-dependent, nucleated process. Alpha-synuclein inhibited
      phospholipase D, induced lipid droplet accumulation, and affected vesicle
      trafficking. This readily manipulable system provides an opportunity to dissect
      the molecular pathways underlying normal alpha-synuclein biology and the
      pathogenic consequences of its misfolding.

PMID- 14657501
TI  - Regulation of cell polarity and protrusion formation by targeting RhoA for
      degradation.
AB  - The Rho family of small guanosine triphosphatases regulates actin cytoskeleton
      dynamics that underlie cellular functions such as cell shape changes, migration,
      and polarity. We found that Smurf1, a HECT domain E3 ubiquitin ligase, regulated
      cell polarity and protrusive activity and was required to maintain the
      transformed morphology and motility of a tumor cell. Atypical protein kinase C
      zeta (PKCzeta), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruited
      Smurf1 to cellular protrusions, where it controlled the local level of RhoA.
      Smurf1 thus links the polarity complex to degradation of RhoA in lamellipodia and
      filopodia to prevent RhoA signaling during dynamic membrane movements.

PMID- 14657502
TI  - Redox regulation of germline and vulval development in Caenorhabditis elegans.
AB  - In vitro studies have indicated that reactive oxygen species (ROS) and the
      oxidation of signaling molecules are important mediators of signal transduction.
      We have identified two pathways by which the altered redox chemistry of the clk-1
      mutants of Caenorhabditis elegans acts in vivo on germline development. One
      pathway depends on the oxidation of an analog of vertebrate low density
      lipoprotein (LDL) and acts on the germline through the Ack-related tyrosine
      kinase (ARK-1) kinase and inositol trisphosphate (IP3) signaling. The other
      pathway is the oncogenic ras signaling pathway, whose action on germline as well
      as vulval development appears to be modulated by cytoplasmic ROS.

PMID- 14657503
TI  - RNA leaching of transcription factors disrupts transcription in myotonic
      dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) is caused by a CUGn expansion (n approximately 50
      to 5000) in the 3' untranslated region of the mRNA of the DM protein kinase gene.
      We show that mutant RNA binds and sequesters transcription factors (TFs), with up
      to 90% depletion of selected TFs from active chromatin. Diverse genes are
      consequently reduced in expression, including the ion transporter CIC-1, which
      has been implicated in myotonia. When TF specificity protein 1 (Sp1) was
      overexpressed in DM1-affected cells, low levels of messenger RNA for CIC-1 were
      restored to normal. Transcription factor leaching from chromatin by mutant RNA
      provides a potentially unifying pathomechanistic explanation for this disease.

PMID- 14657504
TI  - MicroRNAs modulate hematopoietic lineage differentiation.
AB  - MicroRNAs (miRNAs) are an abundant class of approximately 22-nucleotide
      regulatory RNAs found in plants and animals. Some miRNAs of plants,
      Caenorhabditis elegans, and Drosophila play important gene-regulatory roles
      during development by pairing to target mRNAs to specify posttranscriptional
      repression of these messages. We identify three miRNAs that are specifically
      expressed in hematopoietic cells and show that their expression is dynamically
      regulated during early hematopoiesis and lineage commitment. One of these miRNAs,
      miR-181, was preferentially expressed in the B-lymphoid cells of mouse bone
      marrow, and its ectopic expression in hematopoietic stem/progenitor cells led to
      an increased fraction of B-lineage cells in both tissue-culture differentiation
      assays and adult mice. Our results indicate that microRNAs are components of the
      molecular circuitry that controls mouse hematopoiesis and suggest that other
      microRNAs have similar regulatory roles during other facets of vertebrate
      development.

PMID- 14657505
TI  - Finite-frequency tomography reveals a variety of plumes in the mantle.
AB  - We present tomographic evidence for the existence of deep-mantle thermal
      convection plumes. P-wave velocity images show at least six well-resolved plumes
      that extend into the lowermost mantle: Ascension, Azores, Canary, Easter, Samoa,
      and Tahiti. Other less well-resolved plumes, including Hawaii, may also reach the
      lowermost mantle. We also see several plumes that are mostly confined to the
      upper mantle, suggesting that convection may be partially separated into two
      depth regimes. All of the observed plumes have diameters of several hundred
      kilometers, indicating that plumes convey a substantial fraction of the internal
      heat escaping from Earth.

PMID- 14657507
TI  - Coronary artery disease and the MEF2A transcription factor.
AB  - Coronary artery disease (CAD) that results from lesions of the vascular wall is a
      major cause of myocardial infarction (MI) and stroke. A human pedigree with a
      predisposition to CAD and MI has been shown to harbor a mutation in the MEF2A
      transcription factor. These findings reveal a new function for this regulator of
      cardiovascular development and raise intriguing questions about the underlying
      mechanisms of CAD.

PMID- 14657506
TI  - Kinesin moves by an asymmetric hand-over-hand mechanism.
AB  - Kinesin is a double-headed motor protein that moves along microtubules in 8
      nanometer steps. Two broad classes of model have been invoked to explain kinesin
      movement: hand-over-hand and inchworm. In hand-over-hand models, the heads
      exchange leading and trailing roles with every step, whereas no such exchange is
      postulated for inchworm models, where one head always leads. By measuring the
      stepwise motion of individual enzymes, we find that some kinesin molecules
      exhibit a marked alternation in the dwell times between sequential steps, causing
      these motors to "limp" along the microtubule. Limping implies that kinesin
      molecules strictly alternate between two different conformations as they step,
      indicative of an asymmetric, hand-over-hand mechanism.

PMID- 14657508
TI  - Does the road to muscle rejuvenation go through Notch?
AB  - The capacity of skeletal muscles to repair and regenerate declines during aging
      in humans, and this decline may lead to muscle loss and frailty. Conboy et al.
      show that injured muscles of aging mice are defective in Notch signaling, because
      up-regulation of the Notch ligand, Delta-1, is impaired. Delta-1 promotes
      proliferation of the satellite cells that repair damaged muscles, and Conboy et
      al. show that experimental activation of Notch signaling is sufficient to reverse
      the age-related decline in muscle regenerative capacity. Extension of these
      important findings to humans could lead to the development of new therapeutic
      approaches to maintain muscle function during aging.

PMID- 14657509
TI  - The impact of escalating conventional therapy in rheumatoid arthritis patients
      referred for anti-tumour necrosis factor-alpha therapy.
AB  - OBJECTIVE: To assess the impact of escalating conventional therapy in patients
      with RA who satisfy BSR/NICE criteria for biologics. METHODS: A total of 308
      consecutive patients referred to a tertiary centre for biological therapy between
      January 1999 and February 2001 were studied prospectively. They were considered
      by their own consultant to have failed standard therapy. Prior to biologics,
      conventional therapy was escalated to include combination and parenteral
      methotrexate treatment. Patients were assessed at 12-weekly intervals for 1 yr
      and therapy was changed if response was not satisfactory. The subsequently
      released BSR/NICE biologic eligibility criteria were applied retrospectively.
      Response (disease activity, disability and quality of life) to escalated therapy
      in those patients who did or did not satisfy current eligibility criteria were
      compared. RESULTS: In total, 159 satisfied BSR/NICE criteria and would have been
      eligible for immediate treatment with biologics [DAS28 > 5.1, failed methotrexate
      (20 mg/week or lower dose owing to toxicity) and one other DMARD]; however, 93 of
      these responded to escalated conventional therapy and did not require biologics
      [significant improvement (P < 0.01) in disease activity, disability and quality
      of life]. However, mild disease activity (DAS28 < 3.2) was only achieved in 7% of
      these patients at 12 months. CONCLUSIONS: Although over half the patients who
      satisfied standard criteria for biologics responded satisfactorily to escalated
      therapy, only a minority achieved mild disease activity. The savings achieved by
      treating with conventional therapies need to be weighed against the risk of
      persistent disease activity.

PMID- 14657510
TI  - Vasoactive intestinal peptide modulates proinflammatory mediator synthesis in
      osteoarthritic and rheumatoid synovial cells.
AB  - OBJECTIVE: Vasoactive intestinal peptide (VIP) has demonstrated beneficial
      effects in several murine models of immune-mediated inflammation by inhibiting
      both the inflammatory and the autoimmune components of the disease. We
      investigate its potential to modulate the release of proinflammatory cytokines
      and chemokines by human synovial cells from patients with rheumatoid arthritis
      (RA). METHODS: Fresh suspensions of synovial tissue cells (STC) or cultured
      fibroblast-like synoviocytes (FLS) were obtained from patients with RA or
      osteoarthritis (OA). The effects of VIP on basal or tumour necrosis factor alpha
      (TNF-alpha)-stimulated production of CCL2 (MCP-1, monocyte chemotactic protein
      1), CXCL8 [interleukin (IL)-8], IL-6 and TNF-alpha were studied by specific
      ELISAs (enzyme-linked immunosorbent assays). The mRNAs for CCL2, CXCL8 and IL-6
      in FLS were analysed by real-time reverse transcription-polymerase chain
      reaction. RESULTS: VIP at 10 nm down-regulated chemokine production by STC and
      FLS from RA and OA patients. VIP also down-regulated the expression of mRNAs for
      CCL2, CXCL8 and IL-6. The effects of VIP were more clearly detected in RA samples
      and after stimulation with TNF-alpha. CONCLUSION: Our observations confirm that
      the proposed anti-inflammatory actions of VIP in murine models also apply to
      human synovial cells ex vivo. Further studies are encouraged to evaluate the use
      of VIP as a potential therapy for chronic inflammatory joint diseases.

PMID- 14657511
TI  - Consequences of xenoestrogen exposure on male reproductive function in spottail
      shiners (Notropis hudsonius).
AB  - There is limited information on the physiological consequences associated with
      exposure to xenoestrogens under field conditions. The objectives of this study
      were to determine the presence of estrogenic chemicals in the St. Lawrence River
      and their effects on male reproduction in the spottail shiner (Notropis
      hudsonius). Hepatic vitellogenin (VTG) mRNA levels in immature shiners indicate
      extensive estrogenic contamination spanning almost 50 km both upstream and
      downstream from the island of Montreal. Stages of spermatogenesis were assessed
      in fish captured at sites having varying levels of estrogenic contamination. In
      control fish, 95% had testis of either stage IV (50%) or stage V (45%) of
      spermatogenesis. At Ile Dorval, where VTG mRNA levels are moderate, fish had
      testes of stage III (38%) and IV (45%) and only 15% of fish were at spermatogenic
      stage V. In contrast, at Ilet Vert and Ile Beauregard, located in the sewage
      effluent plume from the City of Montreal and where hepatic VTG mRNA levels are
      high in fish, none of the fish were at stage V and 8% of fish at Ilet Vert were
      at stage II of development. Sperm concentration and various motility parameters
      were significantly lower in shiners from Ilet Vert as compared with those from
      Iles de la Paix (reference). Histological analyses of testes revealed that more
      than one-third of the fish captured at sites with the highest estrogenic
      contamination displayed intersex, a condition in which ovarian follicles were
      developing within the testis. These data indicate that there is significant
      estrogenic contamination in the St. Lawrence River that is associated with
      impaired reproductive function in male fish.

PMID- 14657512
TI  - The utility of genetically modified mouse assays for identifying human
      carcinogens: a basic understanding and path forward. The Alternatives to
      Carcinogenicity Testing Committee ILSI HESI.
AB  - The Alternatives to Carcinogenicity Testing Committee of the International Life
      Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI)
      conducted a large-scale, multinational collaborative research program to evaluate
      several genetically modified mouse assays for assessing the human carcinogenic
      potential of compounds. The data from this testing program have made an important
      contribution to the general understanding of how these models can be best applied
      in hazard identification; however, questions still exist regarding methodology
      and data interpretation. To address these issues, ILSI HESI hosted a February
      2003 workshop on the Utility of Transgenic Assays for Risk Assessment. The
      purpose of this workshop was to reach an understanding of how data from
      genetically modified mouse models are viewed by different regulatory bodies in
      the pharmaceutical sector and, based on this understanding, to identify areas in
      which more experimental work may be needed to increase the utility of data
      derived from these assays. In the course of discussions, various data gaps
      related to model selection and protocol issues were identified. Based on the
      outcome of the workshop, various studies are proposed to provide data to improve
      the utility of currently available assays for cancer hazard identification and
      risk assessment purposes.

PMID- 14657513
TI  - Suppression of cell-mediated immune responses to listeria infection by repeated
      exposure to diesel exhaust particles in brown Norway rats.
AB  - Diesel exhaust particles (DEP) have been shown to alter pulmonary immune
      responses to bacterial infection. Exposure of rats to 100 mg/m(3) DEP for 4 h was
      found to aggravate Listeria monocytogenes(Listeria) infection at 3 days
      postinfection, but the bacteria were largely cleared at 7 days postinfection due
      to the development of a strong T cell-mediated immunity. In the present study, we
      examined the effects of repeated DEP exposure at lower doses on pulmonary
      responses to bacterial infection. Brown Norway rats were exposed to DEP by
      inhalation at 20.62 +/- 1.31 mg/m 3 for 4 h/day for 5 days, followed by
      intratracheal inoculation with 100,000 Listeria at 2 h after the last DEP
      exposure. DEP-exposed rats showed a significant increase in lung bacterial load
      at both 3 and 7 days postinfection. The repeated DEP exposure was shown to
      suppress both the innate, orchestrated by alveolar macrophages (AM), and T cell
      mediated responses to Listeria. DEP inhibited AM production of interleukin- (IL-)
      1beta, tumor necrosis factor- (TNF-) alpha, and IL-12 but enhanced Listeria
      induced AM production of IL-10, which has been shown to prolong the survival of
      intracellular pathogens such as Listeria. DEP exposure also suppressed the
      development of bacteria-specific lymphocytes from lung-draining lymph nodes, as
      indicated by the decreased numbers of T lymphocytes and their CD4(+) and CD8(+)
      subsets. Furthermore, the DEP exposure markedly inhibited the Listeria-induced
      lymphocyte secretion of IL-2 at day 7, IL-10 at days 3 and 7, and interferon-
      (IFN-) gamma at days 3 to 10 postinfection when compared to air-exposed controls.
      These results show a sustained pattern of downregulation of T cell-mediated
      immune responses by repeated low-dose DEP exposure, which is different from the
      results of a single high-dose exposure where the acute effect of DEP aggravated
      bacteria infection but triggered a strong T cell-mediated immunity.

PMID- 14657514
TI  - Hexachlorobenzene-induced Immunopathology in Brown Norway rats is partly mediated
      by T cells.
AB  - Hexachlorobenzene (HCB) is a persistent environmental pollutant with (auto)immune
      effects in humans and rats. The Brown Norway (BN) rat is very susceptible to HCB
      induced immunopathology, and oral exposure causes inflammatory skin and lung
      lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of
      IgE and anti-ssDNA IgM. The role of T cells in HCB-induced immunopathology is
      unclear and to elucidate this Cyclosporin A (CsA) was used. BN rats were exposed
      to either a control diet or a diet supplemented with 450 mg/kg HCB for 21 days.
      CsA treatment started 2 days prior to HCB exposure and rats were injected daily
      with 20 mg/kg body weight CsA. Treatment with CsA prevented the HCB-induced
      immunopathology significantly. The onset of skin lesions was delayed and the
      severity was also strongly decreased. Furthermore, CsA prevented the HCB-induced
      increase in spleen weight partly and the increase in auricular LN weight
      completely. The increase in serum IgE and IgM against ssDNA levels was prevented
      completely. Macrophage infiltrations into the spleen and lung still occurred but
      infiltrations of eosinophilic granulocytes into the lung were prevented.
      Restimulation of spleen cells with the T-cell mitogen ConA and the macrophage
      activator LPS clearly showed that CsA inhibited T-cell activation, but not
      macrophage activation. Together, our results show that both T cells and
      macrophages play a prominent role in HCB-induced immunopathology.

PMID- 14657515
TI  - A physiologically based toxicokinetic model for dietary uptake of hydrophobic
      organic compounds by fish: I. Feeding studies with 2,2',5,5'-tetrachlorobiphenyl.
AB  - A physiologically based toxicokinetic (PBTK) model was developed to describe
      dietary uptake of hydrophobic organic compounds by fish. The gastrointestinal
      (GI) tract was modeled using four compartments corresponding to the stomach,
      pyloric ceca, upper intestine, and lower intestine, and the lumenal volume of
      each compartment was allowed to change in time as a function of bulk flow down
      the GI tract and (for the pyloric ceca and upper intestine) nutrient uptake. The
      model was developed using data from rainbow trout that were fed a single meal of
      60-day-old fathead minnows contaminated with [UL-(14)C] 2,2',5,5'
      tetrachlorobiphenyl ([(14)C] PCB 52). Chemical partitioning coefficients for the
      gut contents and tissues were adjusted to account for changes in chemical
      affinity associated with uptake of dietary lipid. Permeability constants for the
      absorbing gut segments were then fitted by modeling to measured [(14)C] PCB 52
      concentrations in gut contents and tissues. The model accurately describes
      observed patterns of gastric evacuation and bulk flow of digesta, the
      concentration time course for [(14)C] PCB 52 in contents and tissues of the GI
      tract, and [(14)C] PCB 52 distribution to other major tissues. Most of the
      [(14)C] PCB 52 was taken up in the pyloric ceca and upper intestine during the
      period of peak lipid absorption. It is concluded, however, that a kinetic
      limitation acting along the entire length of the GI tract resulted in a chemical
      disequilibrium between feces and tissues of the lower intestine.

PMID- 14657516
TI  - A physiologically based toxicokinetic model for dietary uptake of hydrophobic
      organic compounds by fish: II. simulation of chronic exposure scenarios.
AB  - A physiologically based toxicokinetic (PBTK) model for dietary uptake of
      hydrophobic organic compounds by fish was used to simulate dosing scenarios
      commonly encountered in experimental and field studies. Simulations were
      initially generated for the model compound [UL-(14)C] 2,2',5,5'
      tetrachlorobiphenyl ([(14)C] PCB 52). Steady-state exposures were simulated by
      calculating chemical concentrations in tissues of the predator corresponding to
      an equilibrium distribution between the fish and water (termed the
      bioconcentration or BCF residue data set). This residue data set was then varied
      in a proportional manner until whole-body chemical concentrations exhibited no
      net change for each set of exposure conditions. For [(14)C] PCB 52, the
      proportional increase in BCF residues (termed the biomagnification factor or BMF)
      required to achieve steady state in a food-only exposure was 2.24, while in a
      combined food and water exposure the BMF was 3.11. Additional simulations for the
      food and water exposure scenario were obtained for a set of hypothetical organic
      compounds with increasing log K(OW) values. Using gut permeability coefficients
      determined for [(14)C] PCB 52, predicted BMFs increased with chemical log K(OW),
      achieving levels much higher than those reported in field sampling efforts. BMFs
      comparable to measured values were obtained by reducing permeability coefficients
      within each gut segment in a log K(OW)-dependent manner. This predicted decrease
      in chemical permeability is consistent with earlier work, suggesting that dietary
      absorption of hydrophobic compounds by fish is controlled in part by factors that
      vary with chemical log K(OW). Relatively low rates of metabolism or growth were
      shown to have a substantial impact on steady-state biomagnification of chemical
      residues.

PMID- 14657517
TI  - Prevention by methionine of dichloroacetic acid-induced liver cancer and DNA
      hypomethylation in mice.
AB  - Dichloroacetic acid (DCA) is a liver carcinogen that induces DNA hypomethylation
      in mouse liver. To test the involvement of DNA hypomethylation in the
      carcinogenic activity of DCA, we determined the effect of methionine on both
      activities. Female B6C3F1 mice were administered 3.2 g/l DCA in their drinking
      water and 0, 4.0, and 8.0 g/kg methionine in their diet. Mice were sacrificed
      after 8 and 44 weeks of exposure. After 8 weeks of exposure, DCA increased the
      liver/body weight ratio and caused DNA hypomethylation, glycogen accumulation,
      and peroxisome proliferation. Methionine prevented completely the DNA
      hypomethylation, reduced by only 25% the glycogen accumulation, and did not alter
      the increased liver/body weight ratio and the proliferation of peroxisomes
      induced by DCA. After 44 weeks of exposure, DCA induced foci of altered
      hepatocytes and hepatocellular adenomas. The multiplicity of foci of altered
      hepatocytes/mouse was increased from 2.41 +/- 0.38 to 3.40 +/- 0.46 by 4.0 g/kg
      methionine and decreased to 0.94 +/- 0.24 by 8.0 g/kg methionine, suggesting that
      methionine slowed the progression of foci to tumors. The low and high
      concentrations of methionine reduced the multiplicity of liver tumors/mouse from
      1.28 +/- 0.31 to 0.167 +/- 0.093 and 0.028 +/- 0.028 (i.e., by 87 and 98%,
      respectively). Thus, the prevention of liver tumors by methionine was associated
      with its prevention of DNA hypomethylation, indicating that DNA hypomethylation
      was critical for the carcinogenic activity of DCA.

PMID- 14657518
TI  - 15-deoxy prostaglandin J2 enhances allyl alcohol-induced toxicity in rat
      hepatocytes.
AB  - Allyl alcohol causes hepatotoxicity that is potentiated by small doses of
      bacterial lipopolysaccharide (LPS) through a cyclooxygenase-2 (COX-2)-dependent
      mechanism. The COX-2 product prostaglandin D(2) (PGD(2)) increases hepatocyte
      killing by allyl alcohol in vitro. In the present study the ability of the
      nonenzymatic product of PGD(2), 15-deoxy-Delta12,14-prostaglandin J(2) (15d
      PGJ(2)), to increase the cytotoxicity of allyl alcohol was evaluated. In a
      concentration-dependent manner, 15d-PGJ(2) significantly augmented cell death
      caused by allyl alcohol in isolated rat hepatocytes. 15d-PGJ(2) also increased
      the cytotoxicity of acrolein, the active metabolite of allyl alcohol. An agonist
      for the PGD(2) receptor neither reproduced the increase in allyl alcohol-mediated
      cytotoxicity nor altered the response to 15d-PGJ(2). Similarly, these responses
      were not affected by either an agonist or an antagonist for the peroxisome
      proliferator-activated receptor-gamma. The enhancement by 15d-PGJ(2) of allyl
      alcohol-mediated cell killing was unaffected by augmentation or inhibition of
      cAMP. Protein synthesis was markedly decreased by 15d-PGJ(2), but inhibition of
      protein synthesis alone with cycloheximide did not increase allyl alcohol
      mediated cell killing. Allyl alcohol at subtoxic concentrations increased
      translocation of nuclear factor kappa B (NF-kappaB), whereas at cytotoxic
      concentrations no translocation occurred. 15d-PGJ(2) inhibited translocation of
      NF-kappaB from the cytosol to the nucleus both in the presence and absence of
      allyl alcohol. Like 15d-PGJ(2), MG132, an inhibitor of NF-kappaB activation,
      enhanced allyl alcohol-induced hepatocyte death. Together these results indicate
      that 15d-PGJ(2) augments hepatocyte killing by allyl alcohol, and the mechanism
      may be related to the inhibition of NF-kappaB activation.

PMID- 14657519
TI  - Structure-activity and interaction effects of 14 different pyrethroids on voltage
      gated chloride ion channels.
AB  - We have proposed that since the type II pyrethroids deltamethrin and
      cypermethrin, but not the type I pyrethroid cismethrin act on chloride channels,
      this could contribute to the bimodal nature of pyrethroid poisoning syndromes. We
      now examine a wider range of pyrethroid structures on the activity of these
      calcium-independent voltage-gated maxi-chloride channels. Excised inside-out
      membrane patches from differentiated mouse neuroblastoma cells were used, and
      mean channel open probabilities calculated. For single dosing at 10 microM,
      bioallethrin, beta-cyfluthrin, cypermethrin, deltamethrin, and fenpropathrin were
      all found to significantly decrease open channel probability (p < 0.05).
      Bifenthrin, bioresmethrin, cispermethrin, cisresmethrin, cyfluthrin isomers 2 and
      4, lambda-cyhalothrin, esfenvalerate, and tefluthrin, did not significantly alter
      open channel probability (p > 0.05). Since the type II pyrethroids,
      esfenvalerate, and lambda-cyhalothrin were ineffective, we must conclude that
      actions at the chloride ion channel target cannot in themselves account for the
      differences between the two types of poisoning syndrome. Sequential dosing with
      type II pyrethroids caused no further chloride ion channel closure. The type I
      pyrethroid cisresmethrin did however prevent a subsequent effect by the mixed
      type pyrethroid fenpropathrin. In contrast, the type I pyrethroid cispermethrin
      did not prevent a subsequent effect due to the type II pyrethroid deltamethrin.
      The difference in effect may be the result of differences in potency, as
      deltamethrin had a greater effect than fenpropathrin. It therefore appears clear
      that in some combinations the type I and type II pyrethroids can compete and may
      bind to the same chloride channel target site.

PMID- 14657520
TI  - Comparative study on cardiotoxic effect of Tinuvin 770: a light stabilizer of
      medical plastics in rat model.
AB  - Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate], is a UV light
      stabilizer plastic additive used worldwide. It is a component of many plastic
      materials used in medical and food industries. Earlier studies demonstrated its
      in vitro L-type Ca2+ channel and nicotinic acetylcholine receptor blocking
      properties. Our previous experiments have proved the toxic effects of Tinuvin 770
      on isolated rat cardiomyocytes. The present study investigates the cardiotoxic
      effects of Tinuvin 770 in vivo. Wistar rats were intraperitoneally injected with
      increasing doses of Tinuvin 770 (1, 10, 100 microg, and 1 mg) 15 times during a 5
      week period. Myocardial samples were analyzed by light, electron, and fluorescent
      microscopy. The lead-acetate method was used to detect intracellular Ca2+, and
      glyoxylic acid technique to assess alteration in adrenergic innervation. Focal
      myocytolysis and hypercontraction necrosis could be observed in rats treated with
      higher doses of Tinuvin 770. In these groups, intracellular Ca2+ accumulation and
      increased catecholamine release were detected. Tinuvin 770 not only displays L
      type Ca2+ channel blocking properties, but can also lead to catecholamine
      release, similar to effects of the first generation of L-type Ca2+ channel
      blockers. Morphological results correspond to catecholamine-induced myocardial
      damage. Current literature, as well as our study, indicates that more detailed
      toxicological analysis of Tinuvin 770 should be required, and current regulations
      in medical and food industries should adopt the new results.

PMID- 14657521
TI  - Role of aryl hydrocarbon receptor in mesencephalic circulation failure and
      apoptosis in zebrafish embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and potent
      developmental toxicant in various animals, with developing fish being the most
      sensitive organisms. Although the expression of aryl hydrocarbon receptor (AHR)
      as well as the partner molecule, AHR nuclear translocator (ARNT) in the brain has
      been reported, the effect of TCDD on the brain remains to be clarified in detail.
      Previously, we reported local circulation failure and apoptosis in dorsal
      midbrain caused by TCDD in developing zebrafish. In the present experiments, we
      investigated the effects of morpholino antisense oligos against aryl hydrocarbon
      receptor 2 (zfAHR2) (AHR2-MO) on toxicological endpoints caused by TCDD in
      developing zebrafish. AHR2-MO but not its negative homologue (4mis-AHR2-MO)
      improved TCDD-evoked circulation failure in mesencephalic vein and reduced the
      occurrence of apoptosis in dorsal midbrain, with concomitant inhibition of CYP1A
      induction in vascular endothelium. Injection of bovine serum albumin (BSA) into
      the general circulation, followed by immunohistochemistry with anti-BSA, showed
      that TCDD raised vascular permeability to albumin in dorsal midbrain, which was
      blocked by AHR2-MO and N-acetlycystein. In the absence of TCDD, development of
      embryos injected with AHR2-MO appeared normal at least until 60 h after
      fertilization. It is concluded that AHR2 activation in the vascular endothelium
      of the zebrafish embryo midbrain is involved in the mesencephalic circulation
      failure and apoptosis elicited by TCDD. This is the further evidence that
      vascular endothelium is the target of TCDD in relation to local circulation
      failure and apoptosis in dorsal midbrain.

PMID- 14657522
TI  - The use of zebrafish mutants to identify secondary target effects of
      acetylcholine esterase inhibitors.
AB  - We are confronted with a large and steadily growing number of bioactive
      compounds, including drugs, pesticides, and industrial by-products. The
      assessment of target specificity and potential toxic effect on human health and
      the environment generates a strong demand for robust and cost-effective models
      with high predictive power. We investigated the potential of the zebrafish embryo
      as a whole organism, vertebrate model to assess the specificity of compounds that
      are known to inhibit acetylcholinesterase (AChE). Inhibitors of AChE are widely
      used as drugs and pesticides. By application of simple assays and comparison with
      the phenotype of embryos with genetic lesions in the ache gene, we demonstrate
      that only one of the AChE inhibitors (galanthamine) reproduces the phenotype of
      ache mutant embryos. The other compounds produced additional effects indicating
      secondary targets. Our work demonstrates the power of a genetic system for
      toxicological evaluations. The combination of genetics and transgenesis with the
      other experimental virtues of the zebrafish embryo, such as small size and low
      cost, offers a whole organism platform for medium to high throughput compound
      testing.

PMID- 14657523
TI  - Serum hormone characterization and exogeneous hormone rescue of
      bromodichloromethane-induced pregnancy loss in the F344 rat.
AB  - Previously, we demonstrated that bromodichloromethane (BDCM), a drinking water
      disinfection by-product, causes pregnancy loss in F344 rats when given on
      gestational days (GD) 6-10, encompassing the luteinizing hormone (LH)-dependent
      period of pregnancy (GD 7-10). Pregnancy loss, i.e., full-litter resorption, was
      associated with reduced serum progesterone levels; however, we were unable to
      identify an effect on serum LH. Here, we reevaluated serum LH levels using the
      more sensitive technique, DELFIA(R). We further sought to better define the
      temporal pattern of endocrine disruption caused by BDCM during pregnancy with
      more frequent sampling. Lastly, we attempted to prevent BDCM-induced pregnancy
      loss using exogenous progesterone or human chorionic gonadotropin (hCG), an LH
      agonist. BDCM, in 10% Alkamuls(R), was dosed at 75 mg/kg/day by gavage to F344
      rats on GD 6-10 (plug day = GD 0). BDCM-induced pregnancy loss was associated
      with marked reductions in serum progesterone and LH on GD 10. The decrease in
      serum LH consistently preceded the decrease in progesterone. In the hormone
      replacement studies, BDCM and progesterone were administered on GD 6-10, hCG on
      GD 8-10. BDCM was delivered at 100 mg/kg/day, progesterone at 10 mg/kg twice
      daily, and hCG at 0.5 IU/0.2 ml/rat. Both progesterone and hCG prevented BDCM
      induced pregnancy loss. Thus, BDCM-induced pregnancy loss was associated with
      marked GD-10 reductions in serum LH and corresponding decreases in progesterone.
      Furthermore, coadministration of an LH agonist prevented pregnancy loss,
      supporting the hypothesis that BDCM-induced pregnancy loss in the rat occurs via
      an LH-mediated mode of action.

PMID- 14657524
TI  - Short-term oral toxicity of pentyl ether, 1,4-diethoxybutane, and 1,6
      dimethoxyhexane in male rats.
AB  - Pentyl ether (PE) and two newly synthesized polyoxy ethers, 1,4-diethoxybutane
      (DEB) and 1,6-dimethoxyhexane (DMH), have been proposed as candidate diesel fuel
      additives. To characterize and compare their toxicity and to provide information
      for risk assessment, a 4-week oral study was conducted on these compounds. Male
      Sprague-Dawley rats (288 +/- 20 g) were divided into groups of seven animals
      each, and were administered by gavage low (2 mg/kg body weight), medium (20 mg/kg
      body weight), or high (200 mg/kg body weight) doses of PE, DEB, or DMH,
      respectively, 5 days/week for 4 weeks. Animals in the control group received the
      vehicle (corn oil, 1 ml/100 g body weight) only. At the end of the exposure
      period, relative testis and thymus weights were reduced by 30 and 46%,
      respectively, in animals treated with the high dose of DMH. Significant
      reductions in serum lactate dehydrogenase (LDH), serum uric acid, and blood
      platelet counts were also observed in the high dose of DMH. Serum corticosterone
      was significantly depressed in the high doses of PE and DEB and in the low dose
      of DMH. Serum thiobarbituric acid-reactive substances (TBARS) were decreased (p <
      0.05) in all DMH treatment groups and in the medium and high dose PE and DEB
      groups, while liver TBARS were unaffected by treatment. In the liver, increased
      glutathione (GSH) level and glutathione-S-transferases activity were detected in
      the high dose DMH group. Urinary ascorbic acid levels were markedly increased in
      animals receiving the high doses of PE, DEB, and DMH. Urinary formic acid was
      increased by 13 times in the high dose PE and DEB groups. Testes of all animals
      receiving the high dose of DMH showed a moderate to marked degree of degeneration
      of the seminiferous tubules, including a mild degree of vacuolation. At the same
      time, the epididymis of these animals had substantially reduced sperm density
      with prominent presence of spermatid giant cells. Mild histological changes were
      seen in the liver at all dose levels for all three chemicals. Thyroid effects
      were also observed in the high dose PE and DEB groups and in the medium and high
      dose DMH groups. It was concluded that DMH is the most toxic of the three ethers
      tested, with testicular, epidiymal, and thymic effects being the most prominent
      at 200 mg/kg. Other significant changes included depressed platelet counts and
      serum biochemical changes. Increased production of formic acid, an ocular toxin,
      from PE and DEB treatments may also be of toxicological concern.

PMID- 14657525
TI  - The dilemma of drug development and approval.

PMID- 14657526
TI  - The role of the FDA in the national cancer program: friend or foe?

PMID- 14657527
TI  - SEER: Report (card) to the nation.

PMID- 14657528
TI  - Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on
      prior therapy.
AB  - Bortezomib (formerly PS-341), a promising new drug for the treatment of multiple
      myeloma, recently received accelerated approval from the U.S. Food and Drug
      Administration (FDA) for the therapy of patients with progressive myeloma after
      previous treatment. Two phase II studies of bortezomib used the same schedule of
      twice-weekly i.v. dosing for the first 2 weeks of each 3-week cycle. In a
      randomized study of 54 patients, two doses were compared (1.0 and 1.3 mg/m2) and
      objective responses occurred at both dose levels (23% versus 35%), including one
      complete response in each arm. In the other phase II study, 202 heavily
      pretreated patients (median of six prior therapies) all received the same
      schedule at 1.3 mg/m2. Of 188 evaluable patients, complete responses occurred in
      five (3%) and partial responses occurred in 47 (25%). The median duration of
      response was 365 days. The most clinically relevant adverse events were asthenic
      conditions, nausea, vomiting, diarrhea, thrombocytopenia, and a peripheral
      neuropathy that often was painful. This report highlights the FDA analysis
      supporting the accelerated approval.

PMID- 14657529
TI  - Goals and objectives in the management of metastatic breast cancer.
AB  - Patients with metastatic breast cancer consist of a heterogeneous group of
      patients whose prognoses and clinical courses can vary depending on host factors,
      such as comorbidity and age, and on tumor factors, such as hormone-receptor
      status, grade, and anatomical site of disease. Although the median survival time
      for patients with metastatic breast cancer is 2-4 years, subsets of patients with
      either indolent or limited metastatic disease may have prolonged survival times.
      Further, expectations of treatment, both in terms of efficacy and of toxicity,
      vary greatly based upon the specific treatment, patient characteristics, and
      tumor characteristics. Thus, the goals of treatment for patients with metastatic
      breast cancer are influenced by estimates of prognoses as well as a balance
      between physician and patient preferences regarding efficacy and toxicity
      considerations. Traditionally, objective measures of response and survival have
      been the targeted end points in clinical trial design and in physician selection
      of therapy for metastatic breast cancer. More recently, issues of quality of life
      have surfaced as important end points, especially from the perspective of the
      patient. The decision-making process in selecting the optimal treatment for
      patients with metastatic breast cancer is, therefore, a multidimensional process
      involving subjective as well as objective goals of treatment. Ultimately, the
      benefits of treatment must justify the risks and toxicities of the treatment, and
      the impact of treatment should be measured in relation to specified goals. Both
      physician and patient perspectives are important in establishing the objectives
      of treatment, and this process is optimally an interactive and ongoing process
      throughout the course of disease.

PMID- 14657530
TI  - Update on locally advanced breast cancer.
AB  - Locally advanced breast cancer remains a clinical challenge as the majority of
      patients with this diagnosis develop distant metastases despite appropriate
      therapy. Patients with locally advanced disease encompass a wide range of
      clinical scenarios including advanced primary tumors (stage T4), advanced nodal
      disease (fixed axillary nodes or involvement of ipsilateral supraclavicular,
      infraclavicular, or internal mammary nodes), and inflammatory carcinomas. The
      prognoses of women with locally advanced breast tumors are also heterogeneous and
      depend on tumor size, extent of lymph node involvement, and the presence or
      absence of inflammatory carcinoma. Women with locally advanced disease require
      multimodal therapy, and coordinated treatment planning among the medical
      oncologist, surgical oncologist, and radiation oncologist is necessary to
      optimize patient care. In this article, the epidemiology, evaluation, prognostic
      factors, and treatment for locally advanced breast cancer are discussed.
      Inflammatory cancer is also reviewed, but is considered separately due to its
      distinct biology and clinical behavior.

PMID- 14657531
TI  - Activation of tyrosine kinases in cancer.
AB  - Receptor and nonreceptor tyrosine kinases (TKs) have emerged as clinically useful
      drug target molecules for treating certain types of cancer. Epidermal growth
      factor receptor (EGFR)-TK is a transmembrane receptor TK that is overexpressed or
      aberrantly activated in the most common solid tumors, including non-small cell
      lung cancer and cancers of the breast, prostate, and colon. Activation of the
      EGFR-TK enzyme results in autophosphorylation, which drives signal transduction
      pathways leading to tumor growth and malignant progression. Randomized clinical
      trials of the EGFR-TK inhibitor gefitinib have demonstrated clinical benefits in
      patients with advanced non-small cell lung cancer whose disease had previously
      progressed on platinum- and docetaxel-based chemotherapy regimens. Bcr-Abl is a
      constitutively activated nonreceptor TK enzyme found in the cytoplasm of
      Philadelphia chromosome-positive leukemia cells. STI571 (imatinib mesylate)
      inhibits the Bcr-Abl TK, blocks the growth of these leukemia cells, and induces
      apoptosis. STI571 also inhibits other TKs, including the receptor TK c-kit, which
      is expressed in gastrointestinal stromal tumors. As TK inhibitors become
      available for clinical use, new challenges include predicting which patients are
      most likely to respond to these targeted TK inhibitors. Additional clinical
      trials are needed to develop the full potential of receptor and nonreceptor TK
      inhibitors for cancer treatment.

PMID- 14657532
TI  - Measuring progress in cancer control: a bird's eye view.

PMID- 14657533
TI  - Cancer survival and incidence from the Surveillance, Epidemiology, and End
      Results (SEER) program.
AB  - An overview of data on cancer at all sites combined and on selected, frequently
      occurring cancers is presented. Descriptive cancer statistics include average
      annual Surveillance, Epidemiology, and End Results (SEER) Program incidence, U.S.
      mortality and median age at diagnosis, and death for the period 1996-2000.
      Changes during the time period 1992-2000 are summarized by the annual percent
      change in SEER incidence and U.S. mortality data for this period. Five-year
      relative survival for selected cancers is examined by stage at diagnosis, based
      on data from 1990-1999. In addition, 5-year conditional survival for patients
      already surviving for 1-3 years after diagnosis is discussed as well as relative
      survival for other time periods. These measures may be more meaningful for
      clinical management and prognosis than 5-year relative survival from time of
      diagnosis. The likelihood of developing cancer during one's lifetime is 1 in 2
      for males and 1 in 3 for females, based on 1998-2000 data. It is estimated that
      approximately 9.6 million people in the U.S. who have had a diagnosis of cancer
      are alive. Five-year relative survival varies greatly by cancer site and stage at
      diagnosis, and tends to increase with time since diagnosis. The median age at
      cancer diagnosis is 68 for men and 65 for women. The 5-year relative survival
      rate for persons diagnosed with cancer is 62.7%, with variation by cancer site
      and stage at diagnosis. For patients diagnosed with cancers of the prostate,
      female breast, corpus uteri, and urinary bladder, the relative survival rate at 8
      years is over 75%.

PMID- 14657534
TI  - An update on hepatic arterial infusion chemotherapy for colorectal cancer.
AB  - Hepatic metastases are a frequent complication of colorectal cancer (CRC),
      affecting over half of all CRC patients. Resection of isolated metastases can
      result in long-term survival, but the majority of patients relapse, and most have
      unresectable disease. Hepatic arterial infusion (HAI) chemotherapy delivers high
      concentrations of cytotoxic agents directly to liver metastases with minimal
      systemic toxicities. Advances in surgical techniques, development of fully
      implantable pumps, and modification of drug regimens have decreased complications
      and improved patient tolerability. Randomized trials comparing HAI with systemic
      chemotherapy have demonstrated superior response rates and times to hepatic
      progression for unresectable disease, and have shown better times to progression
      and overall survival rates in the adjuvant setting following hepatic resection.
      HAI chemotherapy has unique toxicities, including chemical hepatitis and biliary
      sclerosis, which can be mitigated by the addition of dexamethasone to therapy. In
      an attempt to prevent extrahepatic progression, combinations of HAI with systemic
      chemotherapy, including newer agents such as irinotecan and oxaliplatin, are
      currently being investigated, with promising early results.

PMID- 14657535
TI  - Chronic pain following treatment for cancer: the role of opioids.
AB  - Opioids are the most effective analgesics for severe pain and the mainstay of
      acute and terminal cancer pain treatments. In those settings, opioids are used
      over a limited time period so that opioid tolerance, if it develops, is
      relatively easy to overcome, and other problems of opioid use, including
      substance abuse, are unlikely to be problematic. As cancer treatments improve and
      increasing numbers of cancer patients experience long remissions, chronic pain
      due to cancer, or to cancer treatment, becomes a clinical problem that
      oncologists will encounter. Chronic pain differs from acute and terminal pain in
      several fundamental respects. In the case of chronic pain, functional restoration
      is a predominant goal of treatment. Because it is often due to neuronal damage,
      the pain may be particularly sensitive to nonopioid medications, and opioids can
      be reserved for refractory pain. If opioids are chosen, tolerance, dependence,
      and addiction can interfere, and safeguards designed to minimize these must be
      built into the treatment plan. This article reviews the principles of chronic
      opioid therapy for non-cancer pain and how these principles may be adapted for
      patients with chronic pain due to cancer.

PMID- 14657536
TI  - Small-molecule epidermal growth factor receptor tyrosine kinase inhibitors.
AB  - The growth and proliferation of cells are usually tightly regulated processes
      that are activated by stimuli from their environment. Epidermal growth factor
      (EGF)-related peptides represent a class of molecules that can trigger cell
      proliferation, among several cellular processes, such as differentiation,
      migration, and survival. Binding of EGF-like peptides to the EGF receptor (EGFR)
      at the cell surface leads to a cascade of intracellular reactions that transduce
      signals to the nucleus, resulting in particular gene expression patterns.
      However, in many tumor cells, the regulation of EGFR activity is lost, due to
      increased or aberrant expression of the receptor or its ligands, and this
      contributes to many processes important for tumor growth, including cell
      proliferation, survival, angiogenesis, invasion, and metastasis. Many strategies
      have been developed that specifically target the EGFR and inhibit its activity.
      Of these, small-molecule tyrosine kinase inhibitors represent one of the most
      promising classes of anticancer agents. Here, we describe the status of small
      molecule EGFR tyrosine kinase inhibitors in preclinical and clinical development.

PMID- 14657537
TI  - Breaking bad news: a patient's perspective.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at
      MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and
      advancing compassionate health care delivery that provides hope to the patient,
      support to caregivers, and encourages the healing process. The Center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers, and gain insight and support from fellow staff members.
      Clinicians in the field of oncology are unavoidably forced to break bad news. The
      Schwartz Center Rounds focuses on issues of communication between patients and
      their caregivers, one of the most difficult aspects of which is breaking bad
      news. The invited patient, a woman who had been living with a low-grade cancer
      for many years, spoke about her experiences both as a person living with cancer
      and as the daughter of a patient diagnosed with cancer. Her father's suicide,
      precipitated by being told his diagnosis, puts the horror of receiving bad news
      into stark relief. She provides a fascinating account of how she proactively
      adjusted to her diagnosis, and fought for optimal quality of life. This article
      discusses issues of support, abandonment, and how hope is conveyed, and reviews
      the literature that informs good clinical practice in breaking bad news.

PMID- 14657538
TI  - The molecular perspective: protein farnesyltransferase.

PMID- 14657540
TI  - A "Masterpiece": the life of Paul Calabresi, M.D. (1930-2003).

PMID- 14657541
TI  - A tribute to Paul Calabresi: the man and the Matterhorn.

PMID- 14657543
TI  - Risk factors for fatal subarachnoid hemorrhage: the Japan Collaborative Cohort
      Study.
AB  - BACKGROUND AND PURPOSE: The present study aimed to identify risk factors for
      mortality due to subarachnoid hemorrhage (SAH) using a comprehensive
      questionnaire from the Japan Collaborative Cohort (JACC) Study, a Japan-wide
      population-based prospective study. METHODS: A total of 109,293 individuals
      (45,551 men and 63,742 women, aged 40 to 79 years) free of stroke at entry
      participated in the JACC Study between 1988 and 1990. Participants were followed
      up annually until they died or moved away from the surveyed community, or until
      the end of 1999. A diagnosis of death from SAH was based on the International
      Classification of Diseases, 10th revision (ICD-10). The age-adjusted univariate
      and multivariate hazard ratios (HR) and 95% confidence intervals (CI) of various
      factors were calculated in sex-stratified and sex-specific analyses using the Cox
      proportional hazards regression model. RESULTS: A total of 244 individuals (88
      men and 156 women) died from SAH during the follow-up of 1 086 963 person-years.
      Our univariate analyses confirmed that preference for salty foods and history of
      blood transfusion, as well as hypertension, family history of stroke, cigarette
      smoking, heavy alcohol consumption, and low BMI, had statistically significant
      associations with mortality due to SAH. Multivariable analyses revealed that
      history of blood transfusion was an independent significant risk factor (HR=4.2
      [95%CI, 2.1 to 8.5]) for men, while preference for salty foods or heavy drinking
      were not. CONCLUSIONS: History of blood transfusion was found to be an
      independent risk. The association between SAH and blood transfusion warranted
      further study.

PMID- 14657544
TI  - Intracranial heme metabolism and cerebral vasospasm after aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: The goal of this prospective study was to clarify the
      potential role of an inducible heme-metabolizing enzyme, heme oxygenase (HO)-1,
      and an inducible iron-detoxifying protein, ferritin, in cerebral vasospasm after
      aneurysmal subarachnoid hemorrhage (SAH). METHODS: The authors measured the
      levels of bilirubin and iron, which are by-products of HO-1, and the ferritin
      levels in the cerebrospinal fluid in 39 consecutive patients with aneurysmal SAH
      of Fisher computed tomography group III, and determined the relationship between
      these by-products of HO-1 or ferritin and vasospasm. RESULTS: Fourteen of 39
      patients (35.9%) developed asymptomatic vasospasm, while 6 patients (15.4%)
      developed symptomatic vasospasm. The levels of ferritin, bilirubin, and iron were
      all significantly elevated after SAH. The levels of ferritin and bilirubin were
      significantly higher in patients with no vasospasm than in patients with
      asymptomatic and symptomatic vasospasm on days 5 through 7 (P<0.05, respectively)
      and on days 11 through 14 (P<0.025 in bilirubin) after SAH. However, no
      significant difference was observed in the iron levels between these patient
      groups. CONCLUSIONS: This is the first study to show that higher levels of
      bilirubin and ferritin in the cerebrospinal fluid after SAH were associated with
      no vasospasm in clinical settings. These findings support the concept that the
      induction of HO-1 and ferritin may be an intrinsic regulatory mechanism that acts
      against cerebral vasospasm.

PMID- 14657545
TI  - Prophylactic management of excessive natriuresis with hydrocortisone for
      efficient hypervolemic therapy after subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Hyponatremia caused by excessive natriuresis is common in
      patients with aneurysmal subarachnoid hemorrhage (SAH). Natriuresis decreases the
      total blood volume through osmotic diuresis and increases the risk of symptomatic
      cerebral vasospasm. In such patients, hypervolemic therapy is difficult to
      achieve without causing hyponatremia because sodium replacement provokes further
      natriuresis and osmotic diuresis. We examined the effects of hydrocortisone,
      which promotes sodium retention, in patients with SAH. METHODS: Twenty-eight SAH
      patients were randomized into 2 groups after direct surgery: group 1 patients
      without hydrocortisone treatment (n=14) and group 2 patients with hydrocortisone
      treatment (1200 mg/d for 10 days; n=14). Both groups underwent hypervolemic
      therapy by aggressive sodium and water replacement. The goal of the hypervolemic
      therapy was to maintain the serum sodium level >140 mEq/L and the central venous
      pressure (CVP) within 8 to 12 cm H2O. RESULTS: Group 2 demonstrated a lower
      sodium excretion (P<0.05) and higher serum sodium level (P<0.05) compared with
      group 1. Hyponatremia developed in 6 patients (43%) in group 1 and 0 patients in
      group 2 (P<0.05). Group 2 also demonstrated a lower urine volume, lower infusion
      volume (P<0.05) required for hypervolemic therapy, and higher CVP (P<0.05).
      Failure to maintain CVP was observed in 12 patients (86%) in group 1 and 3
      patients (21%) in group 2 (P<0.05). Hydrocortisone caused no serious side
      effects. CONCLUSIONS: Hydrocortisone clearly attenuates excessive natriuresis.
      Prophylactic hydrocortisone administration appears to have a therapeutic value in
      inducing hypervolemia efficiently after SAH.

PMID- 14657547
TI  - Editorial comment--neuroimaging after TIA: a crystal ball?

PMID- 14657546
TI  - Is diabetes mellitus a cardiovascular disease risk equivalent for fatal stroke in
      women? Data from the Women's Pooling Project.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus is an independent risk factor for
      stroke and is associated with a 1.8- to approximately 6-fold increased risk
      compared with nondiabetic subjects. Recent guidelines have classified diabetes as
      a coronary heart disease risk equivalent. Whether diabetes is a cardiovascular
      disease risk equivalent for stroke is not established. METHODS: Data were pooled
      from 9 prospective epidemiological studies in the United States. We followed up
      27,269 women (8.5% diabetic, 2.9% with prior myocardial infarction, 2.3% with
      prior stroke) for an average of 8.3 years, during which 238 stroke deaths were
      observed. RESULTS: Both diabetic subjects without cardiovascular disease and
      nondiabetic subjects with history of prior stroke had a significantly increased
      risk of 10-year stroke mortality compared with nondiabetic subjects without prior
      cardiovascular disease (hazard ratio [HR], 6.77; 95% confidence interval [CI],
      4.56 to 10.05; HR, 3.37; 95% CI, 2.38 to 4.77). History of prior myocardial
      infarction was not associated with long-term stroke mortality (HR, 0.66; 95% CI,
      0.27 to 1.61). After adjustment for risk factors, diabetic subjects had similar
      risk compared with subjects with a history of prior stroke (HR, 1.29; P=0.43).
      CONCLUSIONS: Diabetic subjects without cardiovascular disease have a fatal stroke
      risk similar to that of nondiabetic subjects with a history of prior stroke and
      similar risk factor profile. This suggests that diabetes mellitus may be
      classified as a stroke risk equivalent and may warrant more aggressive treatment
      strategies in the future prevention of stroke.

PMID- 14657548
TI  - Sleep-disordered breathing as a risk factor for cerebrovascular disease: a case
      control study in patients with transient ischemic attacks.
AB  - BACKGROUND AND PURPOSE: The evidence that obstructive sleep apnea/hypopnea (OSAH)
      is a risk factor for ischemic cerebrovascular disease is inconclusive. We
      explored this relationship in transient ischemic attack (TIA) patients because
      they are less likely than stroke patients to have OSAH as a consequence of
      cerebrovascular disease. METHODS: We performed a case-control study among 86
      patients with TIA from a hospital neurovascular clinic, matched for age (+/-5
      years) and sex with controls from the referring local family practice registers.
      RESULTS: Forty-nine of the 86 matched pairs were male and the body mass index was
      similar among cases and controls. The primary outcome measure, the apnea/hypopnea
      index [AHI=number of (apneas+hypopneas)/h slept, measured during overnight
      polysomnography and scored blind to case-control status], was the same for cases
      and controls (21/hour). However, the median number of 4% desaturations during
      sleep was slightly greater in the cases (12/hour) than controls (6/hour, P=0.04).
      There were the expected associations between TIA and higher fibrinogen levels
      (TIA 3.3, control 3.0 g/L, P=0.01), previous myocardial infarction (TIA 22,
      control 6%, P=0.007), a history of ever smoking (TIA 71, control 54%, P=0.01),
      hypertension (TIA 51, control 21%, P=0.001), and raised cholesterol (TIA 27,
      control 10%, P=0.01), with a weak trend for diabetes mellitus (TIA 10, control
      6%, P=0.4). CONCLUSIONS: OSAH does not appear to be strongly associated with
      TIAs.

PMID- 14657549
TI  - Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in
      vascular dysfunction during diabetes.
AB  - BACKGROUND AND PURPOSE: Inducible nitric oxide synthase (iNOS) is a mediator of
      vascular dysfunction during inflammation. The purpose of this study was to test
      the hypothesis that vascular dysfunction during diabetes is dependent on
      expression of iNOS. METHODS: Diabetes was produced in mice with streptozotocin
      (150 mg/kg IP). After 4 to 6 months of diabetes, vasomotor function was examined
      in vitro in carotid arteries from mice with targeted disruption of the gene for
      iNOS (iNOS-deficient mice) and from normal, wild-type (WT) mice. RESULTS:
      Contractile responses of carotid arteries to U46619, a thromboxane A2 analogue,
      were not altered by diabetes in WT mice. Responses to U46619 were increased in
      arteries from diabetic iNOS-deficient mice compared with diabetic WT and
      nondiabetic mice (iNOS-deficient and WT mice). These results indicate that
      expression of iNOS inhibits an increased vasoconstrictor response during
      diabetes. Arteries from nondiabetic WT mice relaxed 83+/-2% (mean+/-SE) in
      response to acetylcholine (1 micromol/L) compared with 58+/-6% in arteries from
      diabetic WT mice (P<0.05 versus nondiabetic mice). In contrast, relaxation of
      carotid arteries to acetylcholine was similar (81+/-4% versus 76+/-6%; P>0.05) in
      iNOS-deficient mice under nondiabetic and diabetic conditions, respectively.
      Thus, diabetes produced impairment of endothelium-dependent relaxation in
      arteries from WT but not iNOS-deficient mice. Endothelium-independent relaxation
      in response to nitroprusside was similar in arteries from all mice. CONCLUSIONS:
      These results provide the first direct evidence that impairment of endothelium
      dependent relaxation during diabetes is dependent on expression of iNOS.

PMID- 14657552
TI  - Interleukin-6 and stroke: cerebral ischemia versus nonspecific factors
      influencing interleukin-6.

PMID- 14657553
TI  - Over-the-counter cough and cold medication use and risk of stroke.

PMID- 14657554
TI  - Tests for hereditary thrombophilia are of limited value in the black population.

PMID- 14657556
TI  - Introduction to the background, principles, and state of the art in suicide gene
      therapy.

PMID- 14657555
TI  - Anti-alpha-fodrin autoantibodies in Moyamoya disease.
AB  - BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a rare entity that results in
      progressive occlusion of the arteries of the circle of Willis, but the
      pathogenesis of MMD is unknown. METHODS: MMD sera (n=32) were tested for anti
      endothelial cell antibodies by enzyme-linked immunoassays and flow cytometric
      analysis. Apoptosis was induced in human umbilical vein endothelial cells by
      tumor necrosis factor-alpha. RESULTS: We found that a high proportion of MMD sera
      had anti-endothelial cell antibodies with apoptotic stimuli. Prominent
      reactivities of MMD sera (72%) with recombinant human alpha-fodrin were observed.
      CONCLUSIONS: Our study demonstrates that MMD sera contain a high incidence of
      anti-alpha-fodrin autoantibodies, providing new insight into the mechanisms of
      occlusion of MMD arteries.

PMID- 14657557
TI  - Introduction to vectors for suicide gene therapy.

PMID- 14657558
TI  - Construction of VNP20009: a novel, genetically stable antibiotic-sensitive strain
      of tumor-targeting Salmonella for parenteral administration in humans.

PMID- 14657559
TI  - Nonreplicating DNA viral vectors for suicide gene therapy: the adenoviral
      vectors.

PMID- 14657560
TI  - Replication-selective oncolytic adenoviruses.

PMID- 14657561
TI  - Retroviral vectors for suicide gene therapy.

PMID- 14657562
TI  - Nonviral liposomes.

PMID- 14657563
TI  - Peptide- and polymer-based gene delivery vehicles.

PMID- 14657564
TI  - Design of prodrugs for suicide gene therapy.

PMID- 14657565
TI  - Cytochrome p450-based gene therapies for cancer.

PMID- 14657566
TI  - Tumor sensitization to purine analogs by E. coli PNP.

PMID- 14657567
TI  - Enzyme-prodrug systems: carboxylesterase/CPT-11.

PMID- 14657568
TI  - Enzyme-prodrug systems: thymidine phosphorylase/5'-deoxy-5-fluorouridine.

PMID- 14657570
TI  - Extracellular beta-glucuronidase for gene-directed enzyme-prodrug therapy.

PMID- 14657569
TI  - Methods to improve efficacy in suicide gene therapy approaches: targeting prodrug
      activating enzymes carboxypeptidase G2 and nitroreductase to different
      subcellular compartments.

PMID- 14657571
TI  - Enhancement of suicide gene prodrug activation by random mutagenesis.

PMID- 14657572
TI  - Combination suicide gene therapy.

PMID- 14657573
TI  - Immune response to suicide gene therapy.

PMID- 14657574
TI  - Targeting cancer with gene therapy using hypoxia as a stimulus.

PMID- 14657575
TI  - Radiation-activated antitumor vectors.

PMID- 14657576
TI  - In vitro and in vivo models for evaluation of GDEPT: quantifying bystander
      killing in cell cultures and tumors.

PMID- 14657577
TI  - Suicide gene therapy in liver tumors.

PMID- 14657578
TI  - Clinical trials with GDEPT: cytosine deaminase and 5-fluorocytosine.

PMID- 14657579
TI  - The nitroreductase/CB1954 enzyme-prodrug system.

PMID- 14657580
TI  - Side effects of suicide gene therapy.

PMID- 14657581
TI  - Antibody-directed enzyme-prodrug therapy.

PMID- 14657582
TI  - Bioreductive prodrugs for cancer therapy.

PMID- 14657583
TI  - The art and science of prognostication in early university medicine.
AB  - Prognosis occupied a more prominent place in the medieval curriculum than it does
      at the modern university. Scholastic discussions were rooted in the Hippocratic
      Aphorisms and shaped by Galen's treatises On Crisis and On Critical Days. Medical
      prediction, as an art dependent on personal skills such as memory and conjecture,
      was taught with the aid of the liberal arts of rhetoric and logic. Scientific
      predictability was sought in branches of mathematics, moving from periodicity and
      numerology to astronomy. The search for certitude contributed to the cultivation
      of astrology; even at its peak, however, astrological medicine did not dominate
      the teaching on prognostication. The ultimate concern, which awaits further
      discussion, was not even with forecasting as such, but with the physician and,
      indeed, the patient.

PMID- 14657584
TI  - Harvey Cushing's paradigmatic contribution to neurosurgery and the evolution of
      his thoughts about specialization.
AB  - The modern era of neurosurgery began in 1879 with the amalgamation of three
      technologies: anesthesia, antisepsis/asepsis, and cerebral localization. However,
      when Harvey Cushing (1869-1939) took his first tentative steps toward a
      neurosurgical career in 1901, the outlook for the field was dismal, because
      mortality and morbidity rates were horrific. For brain tumors, surgical mortality
      rates were 30-50%. I will argue that Cushing made intracranial surgery clinically
      effective, rather than just feasible, by adding a critical fourth technology:
      knowledge and control of intracranial pressure (ICP). During his Wanderjahr in
      Europe (1900-1) Cushing came to understand ICP in biophysical terms. At Johns
      Hopkins, these lessons were quickly translated to acute human traumatic cases
      (1901-4) and then to tumor patients with raised ICP (1903-5). By 1910, he had
      accumulated enough tumor cases (180) to have convincing statistics. His mortality
      rate for tumors was 10-15%. Nonetheless, the successful paradigm was not fully
      instantiated until a community of practitioners formed a neurosurgical society in
      1920. As this process unfolded, Cushing's ideas about specialization also evolved
      in interesting ways.

PMID- 14657585
TI  - From exclusion to expulsion: Mexicans and tuberculosis in Los Angeles, 1914-1940.
AB  - Even before the influx of Mexicans, public health officials in Los Angeles
      constructed very sick and very poor tubercular people as an illegitimate presence
      who not only endangered others but also represented weakness and failure and
      imposed intolerable economic burdens. The identification of tuberculosis with
      Mexicans during the 1920s hardened the perception that they did not belong in Los
      Angeles. Because Mexicans lived and worked in dangerous surroundings, it is
      likely that they bore a very high burden of tuberculosis. Contemporary
      statistics, however, tell us less about the prevalence of disease than about the
      attitudes of health officials. Most were convinced that Mexicans had an innate
      susceptibility to tuberculosis. Concerns about the cost of supporting tubercular
      Mexicans figured prominently in efforts to restrict their immigration in the
      1920s, and in the deportation and repatriation drives of the 1930s.

PMID- 14657586
TI  - Divisions and diversity: the complexities of medical refuge in Britain, 1933
      1948.
AB  - The experiences of medical refugees who came to the United Kingdom from Nazi
      Germany and occupied Europe in the 1930s and 1940s reflect the general
      characteristics of the British response to the refugee crisis. This article
      analyzes the role of the British medical establishment and its interplay with the
      government and refugee aid organizations. Processes of decision making and
      changes of policy are revealed, drawing on the files of the "Aliens Committee" at
      the archive of the British Medical Association, on the private collection of
      Yvonne Kapp, former administrative head of the Medical Department of the Central
      Office for Refugees, and on the medical subseries of the archive of the Society
      for the Protection of Science and Learning. "Divisions" refer to differing
      interests and attitudes of the institutions, organizations and individuals
      involved; "diversity" reflects the response to the various nationalities of
      medical refugees, mainly German, Austrian, Czech, and Polish.

PMID- 14657587
TI  - The treatment of multiple sclerosis in Los Angeles and the United States, 1947
      1960.
AB  - Two sets of multiple sclerosis (MS) patient records located in Los Angeles County
      from the 1940s and 1950s were analyzed within the historical perspective and
      biomedical context of the time. It was found that there were divergent treatment
      patterns, and a continuum of therapeutic activism in the treatment of MS: some
      physicians attempted to intervene aggressively in an attempt to prevent relapses
      or lessen the severity of attacks, while others adopted milder interventions,
      basing their therapeutic decisions on their knowledge of the pathology of MS. As
      long as a physician had a reasonable theory of the pathogenesis of the disease,
      it was thought permissible to experiment with therapies, despite equivocal
      evidence, as long as no harm was done. Indeed, for physicians faced with
      declining and suffering patients, there was a strong emotional imperative to
      attempt treatments without waiting for an agreed-upon proof of efficacy. This was
      sustained, in part, by pressure to treat from many patients who shared their
      physicians' willingness to experiment with treatments.

PMID- 14657588
TI  - Contending medical ideologies and state formation: the nineteenth-century origins
      of medical pluralism in contemporary Colombia.
AB  - This article addresses the encounter between contending medical ideologies in
      nineteenth-century Colombia. The first era of medical pluralism, in colonial
      Latin America, developed from the imposition of Hispanic medicine on existing
      indigenous medical systems through an imperial structure. This produced a
      "colonial medical spectrum" incorporating various medical ideologies that came
      under attack by practitioners of scientific medicine in the 1800s. As scientific
      physicians gained privileged access to state resources, they undertook partially
      successful campaigns to deny Hispanic, homeopathic, and other medical systems the
      right to be practiced. As the state authorized scientific medicine, other
      practices became "popularized," thereby laying the foundation for the medical
      pluralism of contemporary Colombia that juxtaposes "academic" and "traditional"
      medicines.

PMID- 14657589
TI  - Slide on over.

PMID- 14657591
TI  - Gastrointestinal stromal tumors: biology and treatment.
AB  - Scientific knowledge on gastrointestinal stromal tumors (GIST) has dramatically
      progressed over the last 10 years. During this period, this distinct disease
      entity was identified under various acronyms (GIST remaining the most commonly
      used), the molecular basis of disease transformation (i.e. activating c-KIT
      mutations) was identified in sporadic and familial cases, and finally GIST was
      identified as the sarcoma subtype most resistant to chemotherapy in both
      retrospective and prospective studies. Until 2000, surgery was the only reported
      efficient treatment modality in this disease, both in the localized and
      metastatic phase. In 2000, the first GIST patient received Glivec, and in the
      last 3 years, more than 2,000 patients were included in prospective trials
      evaluating this compound in advanced phases. Disease control is initially
      achieved in 80-90% of patients, with only 10-15% of patients dying in the first
      year following the occurrence of metastases, while the median overall survival
      was less than 12 months with previous treatment options. However, there still
      remain several questions regarding long-term outcome, tolerance, cure, dose of
      Glivec, and alternative treatment upon relapse of GIST in patients receiving
      Glivec. Additional follow-up is necessary. Glivec treatment of GIST is the first
      example of an efficient targeted treatment in a solid tumor.

PMID- 14657592
TI  - Elderly patients with advanced non-small cell lung cancer. A pase II study with
      weekly cisplatin and gemcitabine.
AB  - OBJECTIVES: The incidence of non-small cell lung cancer (NSCLC) is increasing
      among the elderly. We studied the toxicity and efficacy of a weekly schedule of
      gemcitabine and cisplatin in elderly patients with advanced NSCLC. METHODS:
      Patients aged 70 years or above with advanced NSCLC were treated in a phase II
      prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days
      1, 8 and 15 every 28 days. RESULTS: Forty-eight patients with a median age of 74
      years (range 70-78) participated in the study. We observed 14 cases with partial
      response, 14 with stable disease and 16 with progressive disease, whilst 4
      patients were not evaluable. By intention-to-treat analysis, partial response
      rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9
      months; 1-year survival probability was 34.4% and median time to progression was
      4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48
      patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had
      grade III-IV anemia. One patient experienced grade III emesis and 2 patients had
      grade III-IV fatigue. CONCLUSIONS: At this dose and schedule the combination of
      gemcitabine and cisplatin appears to be an active and well-tolerated regimen for
      elderly patients with advanced NSCLC.

PMID- 14657593
TI  - Recurrence rate and prognosis of patients with hepatocellular carcinoma that
      developed after elimination of hepatitis C virus RNA by interferon therapy. A
      closed cohort study including matched control patients.
AB  - BACKGROUND: Although hepatocellular carcinoma does develop after sustained
      response to interferon (IFN) in patients with chronic hepatitis C, details on the
      clinical prognosis have not been elucidated yet. PATIENTS AND METHODS: Among 12
      patients with liver cancer arising after hepatitis C virus (HCV) elimination, 10
      patients with potentially curative ablation were prospectively analyzed. Matched
      control patients were chosen from a patient list of surgical resection on the
      basis of age, sex, cancer stage, and severity of liver disease. Control patients
      were recruited with a ratio of 1:4, and all the control patients had positive HCV
      RNA. RESULTS: One (10.0%) of 10 patients with virus elimination and 31 (77.5%) of
      40 control patients eventually developed cancer recurrence during the same follow
      up period. Cancer recurrence rates of the 10 cases and 40 controls were 10.0 and
      55.3% at the 3rd year, and 10.0 and 72.2% at the 5th year, respectively. The
      recurrence rate in the 10 cases of virus elimination was significantly lower than
      that of control patients (p = 0.012). CONCLUSION: Although hepatocellular
      carcinogenesis after elimination of HCV-RNA by IFN treatment did rarely occur,
      the recurrence rate after radical therapy was significantly lower than that of
      untreated or non-responsive patients.

PMID- 14657594
TI  - Effective combination chemotherapy with bimonthly docetaxel and cisplatin with or
      without hematopoietic growth factor support in patients with advanced
      gastroesophageal cancer.
AB  - PURPOSE: A phase II trial was performed to determine the antitumor efficacy and
      tolerance of combined docetaxel and cisplatin with or without hematopoietic
      growth factor support in patients with advanced gastroesophageal cancer. PATIENTS
      AND METHODS: Thirty-seven patients with histologically confirmed metastatic
      gastroesophageal cancer were entered in this trial. Treatment consisted of 4
      weekly courses of docetaxel 50 mg/m(2) and cisplatin 50 mg/m(2) both given on day
      1 and 15. Depending on absolute neutrophil counts on the days of scheduled
      chemotherapeutic drug administration (1,000-2,000/microl), a 5-day course of
      human granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/day was given
      subcutaneously; in addition, if hemoglobin was <12.0 mg/dl, erythropoietin 10,000
      IU was administered subcutaneously 3 times per week. RESULTS: The confirmed
      overall response rate (intent-to-treat) was 46%, including 4 complete responses
      (11%) and 13 partial responses (35%). Eleven patients (30%) had stable disease
      and 9 (24%) progressed while on treatment. The median time to response was 3
      months, the median time to progression was 7 months and the median overall
      survival time was 11.5 months with 16 (43%) patients currently alive. Hematologic
      toxicity was common, though WHO grade 4 neutropenia occurred only in 3 patients.
      Nonhematologic adverse reaction were usually mild to moderate; grade 3 toxicities
      included alopecia in 5 patients (14%), infection in 1 (3%), neutrotoxicity in 2
      (5%) and anaphylaxis in 1 patient. CONCLUSION: Our data suggest that the
      combination of docetaxel and cisplatin with or without G-CSF and/or
      erythropoietin has a promising therapeutic index in patients with advanced
      gastroesophageal cancer.

PMID- 14657595
TI  - Phase II study of gemcitabine plus docetaxel in advanced pancreatic cancer: a
      Hoosier Oncology Group study.
AB  - OBJECTIVE: To determine the response rate, duration of response and survival with
      weekly gemcitabine plus docetaxel in metastatic or unresectable pancreatic
      cancer. METHODS: Forty patients were enrolled, and 38 patients were evaluable for
      survival and toxicity. Thirty-seven patients were evaluable for response. Nine
      patients (24%) had locally advanced disease and 29 (76%) had metastatic disease
      at the time of enrollment. Median Eastern Cooperative Oncology Group performance
      status was 1. Patients received gemcitabine 750 mg/m(2) i.v. and docetaxel 35
      mg/m(2) i.v. weekly for 3 out of 4 weeks for a maximum of 6 cycles. RESULTS:
      Patients received a median of 4 cycles (range 1-6) of chemotherapy. An objective
      response was obtained in 10 patients (27%) with a median duration of 17 weeks.
      Median survival was 7 months, and 1-year survival was 19.3%. Eight patients
      experienced at least one form of grade 4 toxicity and 27 patients experienced at
      least one type of grade 3 toxicity. CONCLUSIONS: The combination of gemcitabine
      and docetaxel is a well-tolerated regimen with clinical efficacy. The ultimate
      role of this combination versus single-agent gemcitabine can only be determined
      by a randomized phase III trial.

PMID- 14657596
TI  - Phase II trial of weekly paclitaxel in previously untreated advanced non-small
      cell lung cancer.
AB  - OBJECTIVE: New effective therapy is desirable for outpatients with advanced non
      small-cell lung cancer (NSCLC). Fractionated administration of paclitaxel may be
      less toxic and more active against NSCLC. The aim of this study was to evaluate
      the activity and toxicity of weekly paclitaxel therapy for chemotherapy-naive
      NSCLC. METHODS: Patients with pathological or cytological diagnosis of NSCLC,
      measurable lesions, and no prior therapy were enrolled. We administered weekly
      infusions of 80 mg/m(2) paclitaxel 3 times in a 4-week cycle. In the absence of
      progressive disease or intolerable toxicity, we treated each patient for a
      minimum of four cycles. RESULTS: Of 35 patients enrolled, 17 patients achieved
      partial response, although no complete responses were observed (response rate
      49%; 95% confidence interval 32-66%). The median survival time was 55 weeks
      (range 6-93 weeks). Grade 3 or 4 leukopenia occurred in only 1 patient (3%).
      Neurotoxicity was the most frequent adverse effect (grades 1 and 2, 26 and 3%,
      respectively). Serious toxicity, observed in 2 patients (6%), was interstitial
      pneumonia, and 1 patient died from sequela. CONCLUSION: Low-dose weekly
      paclitaxel is a promising therapy for advanced NSCLC with high effectiveness and
      low toxicity.

PMID- 14657597
TI  - Changes in the activation and reconstitution of lymphocytes resulting from total
      body irradiation correlate with slowed tumor growth.
AB  - Alterations in cytokine secretion, activation marker expression, and immune cell
      concentrations were investigated at sequential time points following delivery of
      total-body irradiation (TBI) to C57BL/6 mice (n = 64) in the Lewis lung tumor
      model. Significantly slower tumor growth was observed when a 3-Gy dose of TBI was
      administered 2 h prior to tumor implantation (p < 0.05). The antitumor effect was
      correlated with an increased CD4:CD8 T cell ratio and heightened leukocyte
      blastogenesis. TBI was also found to induce an expansion of natural killer (NK)
      cells in the blood and spleen of tumor-bearing animals 10 days after irradiation
      (2.8 x 10(6) NK cells/spleen in test mice compared to 8.9 x 10(5) NK cells/spleen
      in normal control animals). However, no significant differences were found in NK
      cell levels within the tumor tissue. Enhanced production of interleukin (IL)-12
      and IL-18 from spleen supernatants was consistent with an augmentation of the NK
      cell response. Significant reductions in transforming growth factor-beta1 (TGF
      beta1) and vascular endothelial growth factor, both of which are associated with
      immune suppression, were also noted. Furthermore, TBI induced changes in
      expression of CD25 and CD71 activation markers, suggesting that radiation may
      alter tumor surveillance. Taken together, the relative percentages and activation
      status of immune cell compartments support the conclusion that these TBI-induced
      changes function to slow tumor progression.

PMID- 14657598
TI  - Low-dose thalidomide treatment for advanced hepatocellular carcinoma.
AB  - OBJECTIVE: To analyze the efficacy of oral thalidomide in the treatment of
      advanced hepatocellular carcinoma (HCC). METHODS: Sixty-eight patients with
      unresectable and nonembolizable HCC were consecutively enrolled in a
      compassionate treatment program of oral thalidomide. Tumor response and treatment
      related toxicity were prospectively followed. Thalidomide was given at a starting
      dose of 200 mg per day. The dose was gradually escalated in 100-mg steps up to
      600 mg per day if no limiting toxicities developed. RESULTS: Sixty-three patients
      were evaluable for response. One complete and 3 partial responses, defined by
      World Health Organization criteria, were seen, with a response rate of 6.3% (95%
      CI 0-12.5). The duration of response was 50+, 24.6, 11.6+ and 8.7+ weeks,
      respectively. All 4 responders had a dramatic decrease in alpha-fetoprotein
      (alpha-FP) levels. Another 6 of the 42 patients with elevated alpha-FP levels
      before treatment had a more than 50% decrease in their alpha-FP levels after
      thalidomide treatment. Totally 10 patients had an objective response to
      thalidomide. The median overall survival for all of the 68 patients was 18.7
      weeks (95% CI 11.8- 25.6) with a 1-year survival rate of 27.6%. The median
      overall survival of the 10 patients with an objective response to thalidomide was
      62.4 weeks (95% CI 31.2-93.6 weeks). All responders responded at a dose equal to
      or less than 300 mg per day. Toxicities of thalidomide were generally manageable,
      and only 16, 6, and 0 patients developed grade 2, 3, and 4 toxicities,
      respectively. CONCLUSION: Low-dose thalidomide is safe and induces unequivocal
      tumor response in a minority of patients with advanced HCC.

PMID- 14657599
TI  - Prevention of intrahepatic metastasis by curcumin in an orthotopic implantation
      model.
AB  - Curcumin has been shown to have potent anti-metastatic activity, however, its
      mechanism of action is still unclear. Here, we analyzed the anti-metastatic
      mechanism using hepatocellular carcinoma, CBO140C12 cells. Daily oral
      administration of curcumin suppressed intrahepatic metastasis in a dose-dependent
      manner, whereas the growth of implanted tumors was not affected. We next examined
      the effect of curcumin on several metastatic properties in vitro. Curcumin
      inhibited the invasion of tumor cells through Matrigel-coated filters and the
      production of MMP-9. In addition, curcumin significantly inhibited adhesion and
      haptotactic migration to fibronectin and laminin without affecting the expression
      of integrins on the cell surface. Furthermore, the formation of actin stress
      fibers was affected by treatment with curcumin. These results suggested that
      curcumin suppressed the intrahepatic metastasis mediated by the inhibiton of
      several metastatic properties, in which the functional alteration of cytoskeletal
      organization, at least in part, could play an important role.

PMID- 14657600
TI  - Anaplastic oligodendrogliomas: prognostic factors for tumor recurrence and
      survival.
AB  - OBJECTIVES: Anaplastic oligodendrogliomas (AO) are uncommon primary brain tumors
      whose natural history, prognosis, and optimal management are not yet fully
      understood. However, they are associated with a better prognosis and response to
      multimodality therapy based on specific molecular changes. In this multicenter
      retrospective study, we analyzed the clinical characteristics of patients with AO
      to identify prognostic factors that influence time to progression (TTP) and
      survival. METHODS: A retrospective search of the brain tumor databases of three
      institutions (the University of Texas M. D. Anderson Cancer Center, the
      University of California at San Francisco, and the University of Utah) for
      patients between 1977 and 1995 with histologically confirmed AO identified a
      cohort of 106 patients that was further analyzed in this study. Initial treatment
      included surgery alone (n = 12) or surgery followed by one of the following:
      radiotherapy (RT) alone (n = 49), chemotherapy alone (n = 4), chemotherapy
      followed by RT (n = 10), RT followed by chemotherapy (n = 20), and others (n =
      11). RESULTS: The median age at diagnosis was 43 years, and the median Karnofsky
      performance score (KPS) was 90. The overall median survival was 7.3 years, and
      the 5-year survival rate was 62%. Univariate analysis of several clinical
      variables showed that only age (p < 0.0001) and KPS (p = 0.04) correlated
      significantly with survival. Fifty patients had disease progression after initial
      therapy. The median TTP was 48 months. Age at diagnosis was the only variable
      that correlated significantly with TTP. CONCLUSIONS: A trend towards longer
      survival with a greater extent of resection was evident. The relative efficacy of
      various treatment modalities could not be definitively determined because of the
      heterogeneity of the therapies used. Overall, patients with AO have a better
      prognosis after therapy compared with those who have other malignant gliomas.

PMID- 14657601
TI  - Forced expression of cytidine deaminase confers sensitivity to capecitabine.
AB  - OBJECTIVE: Cytidine deaminase (CDD) is involved in the metabolism of new
      pyrimidine analogues, capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5
      fluorocytidine) and gemcitabine (2',2'-difluorodeoxycytidine). The purpose of the
      present study was to directly examine the role of CDD in tumor cells themselves
      in mediating the sensitivity to capecitabine compared with gemcitabine. METHODS:
      The human bladder cancer cell line T24 was transfected with human CDD2 cDNA by
      the lipofectin method. RESULTS: Transfection of CDD2 cDNA did not change the
      levels of thymidine phosphorylase, dihydropyrimidine dehydrogenase and
      thymidylate synthase (TS) but increased the CDD activity significantly (p <
      0.01). Forced expression of CDD made T24 sensitive to 5'-deoxy-5-fluorocytidine
      (5'DFCR) in vitro and capecitabine in vivo, but resistant to gemcitabine both in
      vitro and in vivo. Tetrahydrouridine, a specific CDD inhibitor, abrogated the
      changes in the in vitro sensitivity to 5'DFCR and gemcitabine by transfection of
      CDD2 cDNA. Transfection of CDD2 cDNA resulted in a significant increase in
      cellular 5-fluorouracil level (p < 0.01) and inhibition of TS activity (p < 0.01)
      after treatment with 5'DFCR in vitro. CONCLUSIONS: The present study clearly
      showed direct evidence for the contribution of CDD in tumor cells themselves to
      the sensitivities to capecitabine and gemcitabine.

PMID- 14657602
TI  - Helicobactor pylori infection is closely associated with telomere reduction in
      gastric mucosa.
AB  - OBJECTIVE: To investigate differential reduction in telomere DNA in tissue
      components of gastric mucosa with respect to Helicobactor pylori infection.
      MATERIALS AND METHODS: The telomere content was examined by fluorescent in situ
      hybridization with the (TTAGGG)(4) probe. To compare the signal intensities from
      the probe (telomere volume) with telomere length, five gastric carcinoma cell
      lines were used. Telomere volumes were examined in 9 healthy persons, 124 non
      cancer patients, and 86 gastric cancer patients. RESULTS: Telomere volume showed
      a linear correlation with telomere length measured by Southern blotting in
      gastric carcinoma cells. In healthy persons without H. pylori infection, the
      telomere volumes of gastric epithelial tissues were 70-79% that of intramucosal
      lymphocytes (internal control). In 124 patients without gastric cancer, telomere
      volume of H.-PYLORI-infected mucosa was significantly less than that of H.-pylori
      negative mucosa in both metaplastic and non- metaplastic tissues (p < 0.0001). In
      86 gastric cancer patients, telomere volumes in intestinal metaplasia adjacent to
      cancer were 75% that of intestinal metaplasia of non-cancer patients (p =
      0.0001). hTERT expression was detected in 6 cancer-associated and 2 cancer
      negative intestinal metaplasia specimens, in which telomere volume was markedly
      reduced. CONCLUSION: H. pylori infection is closely associated with telomere
      reduction in gastric epithelium.

PMID- 14657603
TI  - Comparison of low-dose versus standard-dose colony stimulating factor in patients
      with chemotherapy-induced febrile neutropenia.

PMID- 14657604
TI  - Excretion of 6-hydroxymelatonin sulfate (6-OHMS) in siblings during childhood and
      adolescence.
AB  - The analysis was performed to support the assumption that in inter-individual
      variations melatonin production is determined genetically. Sixty-six siblings
      from 31 families (27 girls, 39 boys, 3-18 years) contributed to this study with 3
      to 15 urine samples collected once a year over 24 h. The samples were stored at 
      20 degrees C and analyzed for the daily output of the melatonin metabolite 6
      hydroxymelatonin sulfate (6-OHMS) by an enzyme-linked immunosorbent assay
      (ELISA). The results indicate that 6-OHMS excretion was significantly correlated
      in siblings (r = 0.37, p = 0.01), suggesting a possible genetic background of
      melatonin production. However, prospective studies controlling also lifestyle
      factors such as diet are required to further confirm the hypothesis.

PMID- 14657605
TI  - Neuroendocrinology of neurodegenerative diseases. Insights from transgenic mouse
      models.
AB  - The nervous system plays a key role in the regulation of neuroendocrine axes and,
      in turn, the released neurohormones modulate the activity of different brain
      regions. Neurodegenerative diseases, which are known to affect specific neuronal
      populations, may provoke neuroendocrine dysfunctions that alter the intimate
      relationship between both systems. In addition, these modifications may influence
      the progression of the neurodegenerative process. In the present review, we
      summarise some of the endocrine changes characterising three major
      neurodegenerative diseases: Alzheimer's disease, Parkinson's disease and
      amyotrophic lateral sclerosis. Special attention is focused on the contribution
      of disease transgenic models to elucidate such alterations.

PMID- 14657606
TI  - Brain renin-angiotensin system. Lessons from functional genomics.
AB  - The existence of a brain renin-angiotensin system (RAS) was postulated 30 years
      ago. Since then our knowledge on the biology of the brain RAS has advanced
      considerably. The brain RAS has been found to be involved in the modulation of
      cardiovascular and fluid-electrolyte homeostasis, generally complementing the
      classical roles of the endocrine RAS. The RAS has additionally been implicated in
      other brain-specific functions, such as memory, cognition and stress. During the
      last years, the development of transgenic technologies allowed to get further
      insight into the functionality and relevance of the brain RAS. This paper is
      attempting to summarize our recent experience from transgenic animals.

PMID- 14657607
TI  - Role of K(+) channels in frequency regulation of spontaneous action potentials in
      rat pituitary GH(3) cells.
AB  - The frequency of spontaneous action potentials (SAP) is important in the
      regulation of hormone secretion. The decrease in K(+) conductance is known as a
      primary mechanism for increasing SAP frequency. To investigate the nature of K(+)
      channels that contribute to the frequency regulation of the SAP in rat clonal
      pituitary GH(3) cells, the effect of various K(+) channel blockers on the SAP and
      membrane currents were recorded using the patch-clamp technique. A classical
      inward rectifying K(+) channel blocker, Cs(+) (5 mM), caused an increase in
      firing frequency and depolarization in after-hyperpolarization (AHP) voltage. An
      ETHER-A-GO-GO(ERG) type K(+) channel blocker, E-4031 (5 microM), caused no
      significant effect on the SAP. Tetraethylammonium (TEA, 10 mM) decreased firing
      frequency and increased the duration of SAP. These effects were not changed by
      the presence of high concentration of Ca(2+) buffer (10 mM EGTA or BAPTA) in
      pipette solutions. In voltage-clamp experiments, Cs(+) and E-4031 did not affect
      outwardly rectifying K(+) currents, but significantly inhibited inwardly
      rectifying K(+) currents recorded in isotonic K(+) solution. However, the
      kinetics of Cs(+)-sensitive current and E-4031-sensitive current were
      distinctive: the time to peak was more immediate and the decay rate was slower in
      Cs(+)-sensitive current than in E-4031-sensitive current. These results imply
      that Cs(+) and E-4031 inhibit the distinct components of inwardly rectifying K(+)
      currents, and that the contribution of the Cs(+)-sensitive current can be
      immediate on repolarization and can last more effectively over pacemaking
      potential range than E-4031-sensitive current.

PMID- 14657608
TI  - Modulatory effects of leptin on leydig cell function of normal and
      hyperleptinemic rats.
AB  - Neonatal L-monosodium glutamate (MSG) administration in rats induces several
      neuroendocrine and metabolic disruptions. Leptin, the adipocyte product,
      modulates several neuroendocrine systems including the hypothalamic-pituitary
      gonadal (HPG) axis in mammals. The aim of the present study was to determine
      whether MSG-induced chronic hyperleptinemia could play any relevant role in the
      hypogonadism developed by male rats when examined in adulthood. We found that 120
      day-old MSG male rats displayed significant hyperleptinemia, hypogonadism, and
      undisturbed basic testis structure and spermatogenesis. In vitro studies in
      purified Leydig cells from normal (CTR) and MSG-damaged rats revealed that basal
      and human chorionic gonadotropin (hCG)-stimulated 17-hydroxy-progesterone (17-HO
      P(4)), Delta(4)-androstenedione (Delta(4)A) and testosterone (T) secretions were
      significantly lower in MSG than in CTR cells. Exposure to murine leptin (Mleptin,
      10(-8)M) significantly inhibited hCG-elicited T secretion by CTR cells after 180
      min incubation. While Mleptin significantly inhibited hCG-stimulated Delta(4)A
      output and the Delta(4)A:17-OH-P(4) ratio of secretion, conversely, it failed to
      modify the ratio T:Delta(4)A release by CTR Leydig cells. Interestingly, the
      effects of Mleptin found on CTR Leydig cells were absent in MSG Leydig cells.
      Finally, endogenous hyperleptinemia was associated with a significant decrease in
      Leydig cell expression of Ob-Rb mRNA in MSG rats. In summary, this study
      demonstrates that: (1) Mleptin inhibited testicular steroidogenesis in CTR rats;
      (2) MSG-treated rats showed lower in vitro 17-OH-P(4), Delta(4)A and T production
      under basal and post-hCG stimulation conditions; (3) purified Leydig cells from
      MSG-treated rats displayed resistance to the inhibitory action of Mleptin on T
      release, and (4) endogenous leptin exerts a modulatory effect on Leydig cell Ob
      Rb mRNA expression. The inhibitory effect of leptin on testicular function is
      thus abrogated in MSG-damaged rats. The testicular leptin-resistance developed by
      MSG rats seems to be due to early chronic exposure of Leydig cells to high leptin
      circulating levels, which in turn down-regulate testicular Ob-Rb expression. It
      remains to be determined whether the testicular dysfunction of MSG rats can be
      reversed after correction of hyperleptinemia or whether it is an irreversible
      effect of the hypothalamic lesion.

PMID- 14657609
TI  - Effect of dihydrotestosterone on pituitary follicle-stimulating hormone isoforms
      in adult male rats treated with a gonadotropin-releasing hormone antagonist.
AB  - The effect of androgens on the oligosaccharide structure of follicle-stimulating
      hormone (FSH) isoforms was studied in adult male rats treated with a potent
      gonadotropin-releasing hormone (GnRH) antagonist. Animals were castrated (Cx),
      and 24 h later were treated with physiological doses of either testosterone
      propionate (T) or dihydrotestosterone propionate (DHT) (0.25 mg/rat in corn oil,
      daily, s.c.) for 7 days. The antiandrogen flutamide (F; 5 mg/day/rat, twice a
      day, s.c.) was administered to either Cx-T or Cx-DHT rats to block androgen
      action. The GnRH antagonist Org 30276 (Ant; 1 mg/kg/day, s.c.) was injected to
      both Cx- and Cx-DHT treated rats. FSH serum levels reached normal values in Cx
      rats treated with either T or DHT, whereas those treated with F retained Cx
      conditions. Both Cx-Ant and Cx-Ant-DHT treated animals presented normal serum FSH
      levels. Concanavalin A affinity chromatography was used to isolate pituitary FSH
      isoforms according to their carbohydrate inner structure. An increased proportion
      of FSH isoforms bearing complex-type oligosaccharides was observed in Cx rats
      treated with T or DHT, whereas the proportion of these isoforms was reduced in Cx
      and Cx-T-F or Cx-DHT-F rats. These results demonstrate that functional androgens
      are needed to complete the oligosaccharide processing of FSH. In addition, the
      proportion of the different pituitary FSH isoforms after DHT replacement was
      equivalent to that found when GnRH action was blocked, indicating that androgens
      are involved in the regulation of carbohydrate incorporation to the FSH molecule
      by acting mainly at the pituitary level, independently of GnRH action.

PMID- 14657611
TI  - Metabolic disturbances in shock, and the role of ATP-MgCl2 and sex steroids.
AB  - Hemorrhage following accidental injuries is a common cause of death in the
      industrialized world. Moreover, the impact of elective surgery and solid organ
      transplantation sometimes results in low flow conditions similar to those seen
      following hemorrhagic shock. A shortage in O(2) availability, or hypoxia, leads
      to sequential changes in cell metabolism and morphology, including inflammatory
      responses and the expression of hypoxia-inducible transcription factor-1, which
      controls the cellular adaptation to hypoxia. These endogenous adaptive responses
      show that O(2) deprivation is not an unforeseen event for cells. The purpose of
      this review article is to discuss the pathophysiologic principles of shock and
      the metabolic alterations that cells undergo during low flow conditions.
      Moreover, the rationale for therapeutic intervention by administering ATP-MgCl(2)
      and sex steroids following shock and trauma will also be discussed.

PMID- 14657612
TI  - Streptococcus agalactiae (Group B Streptococci) carriage in late pregnancy in
      Kuwait.
AB  - OBJECTIVES: This study investigated the vaginal colonization rate of
      Streptococcus agalactiae (group B streptococci, GBS) in an antenatal population
      in a maternity hospital. SUBJECTS AND METHODS: Anal, vaginal and combined anal
      and vaginal specimens were obtained from 110 pregnant women (mean age 30.7 +/-
      5.5 years) at 35-37 weeks of gestation, using a commercially prepared culturette,
      and transported in 0.5 ml of Stuart's transport medium. The specimens were then
      cultured in standard selective Todd-Hewitt broth medium, supplemented with
      gentamicin and nalidixic acid. After 36 h of incubation, the broth culture was
      subcultured onto sheep blood agar and incubated in 5% carbon dioxide for 18-24 h.
      Representative colonies morphologically resembling GBS were tested with latex
      agglutination kit. Each culture-positive woman was given ampicillin or
      piperacillin prophylactically and followed up through labour and postpartum.
      Detailed records of biodata, antecedent antenatal events and pregnancy outcome
      were reviewed. RESULTS: The combined vaginal and anal specimens were positive for
      GBS in 18 (16.4%) women. Gestational age at delivery was 39.01 +/- 1.79 weeks.
      The deliveries were uneventful and no neonate developed sepsis. Diabetes mellitus
      and pregnancy-induced hypertension/hypertension were detected antenatally in 16.6
      and 11.5%, respectively. GBS carriage was not associated with adverse outcome of
      pregnancy. CONCLUSION: The colonization rate of GBS in pregnant women in Kuwait
      is high, and on the basis of the documented benefits of antenatal screening in
      Western countries, we recommend routine screening especially for our at-risk
      patients.

PMID- 14657613
TI  - Effect of treadmill exercise on circulating thyroid hormone measurements.
AB  - OBJECTIVES: Effects of exercise on circulating thyroid hormone (TH) values remain
      controversial. We sought to observe the effect of treadmill exercise on serum TH
      values in highly selected subjects. METHODS: Twenty-six healthy male military
      recruits aged 23-27 (mean, 25) years were studied. All had maintained identical
      diet and physical activity for a week before the test. Serum samples were drawn
      before (baseline) and immediately, 1, 4, 24, 24 and 48 h after maximal exercise
      (on a treadmill, Bruce protocol). All subjects completed the protocol with normal
      ECG results. Specimens were analyzed to measure 3,3',5-triiodothyronine (T(3)),
      thyroxine (T(4)), free T(4) (FT(4)), free T(3) and thyroid-stimulating hormone
      (TSH) in the same assays. To determine the possible effect of hemodynamic
      changes, hematocrit (Hct)-adjusted data were also compared. RESULTS:
      Hemoconcentration, as reflected by increased Hct, was found immediately after
      exercise. No significant changes of serum mean TH values before and after
      exercise were found except for TSH, which increased significantly immediately
      after exercise (1.72 vs. baseline 1.42 IU/l, p < 0.01). Values for T(3), T(4),
      and TSH increased significantly immediately after exercise, as compared to other
      postexercise values. However, the changes became insignificant after Hct
      adjustment. The FT(4) values showed a reciprocal increase after exercise that
      became significant after Hct correction. Significantly negative correlation was
      found between FT(4) and TSH values, but these values were still well within the
      normal range. CONCLUSIONS: Maximal treadmill exercise does not greatly affect the
      determination of concentrations of circulating THs.

PMID- 14657614
TI  - Prevalence and severity of symptoms of asthma, allergic rhinoconjunctivitis, and
      atopic eczema in 6- to 7-year-old Nigerian primary school children: the
      international study of asthma and allergies in childhood.
AB  - OBJECTIVE: To determine the prevalence and severity of symptoms of asthma,
      allergic rhinoconjunctivitis and eczema in Nigerian children aged 6-7 years.
      SUBJECTS AND METHODS: A cross-sectional study of selected children in primary
      schools in Ibadan, Nigeria was conducted using phase I of the International Study
      of Asthma and Allergies in Childhood (ISAAC) format. Standardized questionnaires
      were distributed to parents and guardians of 2,325 children aged 6-7 years in 31
      primary schools randomly selected among 272 in Ibadan. RESULTS: Data was
      collected from 1,704 children (797 boys and 907 girls; M:F ratio 1:1.14), giving
      a participation rate of 73.3%. Both recent rhinoconjunctivitis and wheeze were
      reported by 5.1%, and itchy flexural rash in the past 12 months was reported by
      8.5%. The cumulative prevalences of reported symptoms of wheezing, rhinitis and
      eczema were 7.2, 11.3 and 10.1%, respectively. These symptoms were basically the
      same among the boys and girls (rhinitis 11.4 vs. 11.2%; eczema 10.7 vs. 9.5%),
      except for wheezing, which was higher in boys (9.0%) than girls (5.6%), p =
      0.015. Current symptoms of rhinitis and atopic eczema were associated with
      current wheeze and severe wheezing, whereas current symptoms of allergic
      rhinoconjunctivitis were only associated with severe wheezing attacks. One or
      more current symptoms occurred in 13.2% of the children, and all three symptoms
      were reported by 0.5%. CONCLUSION: The study demonstrates a high prevalence of
      atopic conditions among children 6-7 years old in Ibadan, Nigeria, with more than
      three fifths of the children who had current wheezing also showing symptoms of
      other atopic diseases. Children with allergic rhinoconjunctivitis were more
      likely to have severe wheezing attacks if they had developed atopic eczema before
      2 years of age.

PMID- 14657615
TI  - Interleukin-1 and nitric oxide increase NADPH oxidase activity in human coronary
      artery smooth muscle cells.
AB  - OBJECTIVE: Cytokines, nitric oxide (NO) and reactive oxygen species (ROS) are
      well known for their pathogenic effects in development of cardiovascular
      diseases. Interleukin-1beta (IL-1beta) is known to induce NO generation, however
      it is not well established if IL-1beta or NO regulate production of ROS, such as
      superoxide anion. Therefore, the main objective of this study was to evaluate the
      effect of IL-1beta or NO on enzyme activity of NADPH oxidase (NOX), a superoxide
      generating system recently documented to participate in a variety of vascular
      functions. METHODS: Human coronary artery smooth muscle cells (SMC) obtained from
      Clonetics were treated with IL-1beta and NO donor, sodium nitroprusside (SNP), in
      culture. Nitrites accumulated in supernatants of SMC cultures were measured as an
      index of NO released following treatment with IL-1beta. NOX enzyme activity was
      assayed using cytochrome c as the electron acceptor. RESULTS: Treatment with IL
      1beta resulted in a 3-fold increase in the production of NO by SMC. Both IL-1beta
      and SNP enhanced NOX activity, by 67 and 45%, respectively, following 24 h of
      treatment. CONCLUSION: This study suggests that NO or NO- generating cytokines
      might regulate the production of ROS in the cardiovascular system through
      modulation of superoxide-generating systems such as NOX.

PMID- 14657616
TI  - Prevalence of endometrial proliferation in pipelle biopsies in tamoxifen-treated
      postmenopausal women with breast cancer in Kuwait.
AB  - OBJECTIVE: To determine the prevalence of pathologic changes in the endometrium
      of tamoxifen-treated asymptomatic postmenopausal patients with breast cancer.
      SUBJECTS AND METHODS: Fifty postmenopausal asymptomatic breast cancer patients
      with positive estrogen receptor status were treated with 20 mg of tamoxifen daily
      for a period of 5-60 months. The control group consisted of 30 asymptomatic
      postmenopausal breast cancer patients who were negative for estrogen receptor and
      therefore did not receive tamoxifen. Endometrial biopsies were performed using
      Pipelle endometrial suction curette at least 5 months after the study began. The
      endometrium was classified as atrophic (negative finding) and proliferative or
      hyperplastic (positive findings). The study and control groups were compared for
      demographic characteristics, risk factors for endometrial cancer, histological
      findings and the duration of tamoxifen treatment. RESULTS: A significantly
      greater prevalence of endometrial abnormalities existed among the tamoxifen
      treated than control patients (76 vs. 33%, p < 0.001). The abnormal endometrial
      changes were further demarcated in both groups into proliferative (54 vs. 26.7%,
      p = 0.02) and hyperplastic (22 vs. 6.6%, p = NS). In the study group, 63.6% of
      hyperplastic endometrium was simple hyperplasia and 36.4% was complex/no atypia
      hyperplasia, while in the control group all the cases were simple hyperplasia. No
      endometrial cancer was detected in either group. In addition, there was a
      positive association between the duration of tamoxifen exposure (<1 year vs. >/=1
      year) and the endometrial abnormalities (46.6 vs. 88.6%, p = 0.003; proliferative
      57.1 vs. 74.1%, p = 0.015; hyperplastic 42.8 vs. 25.8%, p = NS). CONCLUSION: The
      adjuvant use of tamoxifen is associated with significant time-dependent abnormal
      endometrial changes among patients with cancer of the breast.

PMID- 14657617
TI  - Effect of plasma from patients with Behcet's disease on the production of nitric
      oxide in cultured human umbilical vein endothelial cells.
AB  - OBJECTIVE: To determine the effect of plasma from patients with Behcet's disease
      (BD) on the production of nitric oxide (NO) in cultured human umbilical vein
      endothelial cells (HUVECs). SUBJECTS AND METHODS: NO levels were measured in cell
      culture media after 24-hour incubation of the cells with plasma obtained from 22
      BD patients and 16 age/sex-matched healthy control subjects. After treatment of
      the patients with colchicine and/or nonsteroidal anti-inflammatory drugs, 12 of
      the patients were considered to be in the inactive phase of the disease. Levels
      of NO production were also measured in these 12 patients. In addition to the in
      vitro experiments, erythrocyte sedimentation rate, alpha(1)-antitrypsin, alpha(2)
      macroglobulin and neutrophil counts were measured in the patients and controls.
      RESULTS: Levels of NO in active state BD patients (15.9 micromol/10(6) cells)
      were significantly lower than values obtained from both patients in the inactive
      period (19.2 micromol/10(6) cells) and the control group (19.7 micromol/10(6)
      cells). No significant differences were observed in induced NO products between
      the patients in the inactive stage and control subjects. CONCLUSION: Plasma from
      BD patients decreased the level of NO production in the HUVECs, and therefore may
      cause dysfunction in the endothelial NO synthase activity.

PMID- 14657618
TI  - Prevalence of metabolic syndrome among hypertensive patients attending a primary
      care clinic in Kuwait.
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome among hypertensive
      patients using the criteria of the National Cholesterol Education Program's Adult
      Treatment Panel III in a primary care health center in Kuwait. SUBJECTS AND
      METHODS: A population of 250 Kuwaiti hypertensive patients (129 males and 121
      females) over the age of 40 were screened for metabolic syndrome by determining
      body mass index (BMI), waist circumference, levels of fasting plasma glucose and
      fasting plasma lipids (serum triglycerides, total cholesterol and high-density
      lipoprotein cholesterol). The study was carried out in the Mishref Family
      Practice Health Center, Kuwait, from January to July 2001. RESULTS: The total
      number of patients who met the criteria for metabolic syndrome was 85 (34%), 55%
      of them were males and 45% females. Prevalence of the syndrome was 28.2% among 40
      to 55-year-olds and 41.9% in those above the age of 55 years. Among the 250
      hypertensive patients, type II diabetes mellitus was found in 52.8% (54% males
      and 46% females), impaired fasting glucose in 8% (70% males and 30% females),
      high plasma triglycerides in 44.8% (53% males and 47% females) and low high
      density lipoprotein cholesterol in 63.2% (54% males and 46% females). Obesity
      measured as BMI = 30 kg/m(2) was noted in 46% (43% males and 57% females) and
      increased waist circumference in 58% (44% males and 56% females). CONCLUSION: The
      prevalence of metabolic syndrome is high among hypertensives attending primary
      health care centers in Kuwait.

PMID- 14657619
TI  - Is there a need for Doppler vascular examination for the diagnosis of varicose
      vein? A prospective study.
AB  - OBJECTIVE: To compare the validity of a careful clinical examination with venous
      Doppler studies in the management of patients presenting with varicose veins.
      SUBJECTS AND METHODS: Ninety-five consecutive patients presenting with varicose
      veins from September 1998 to August 1999 were included in this study. Of the 95
      patients, 52 were males and 43 females. Eighty-four were expatriate laborers and
      11 Kuwaiti nationals. Seventy-one were active workers under the age of 30. All of
      the patients underwent a full clinical examination for varicose veins, and a
      management plan was developed for each patient prior to Doppler venous study. The
      results of the Doppler studies were then compared with the clinical examination
      results, and the management plan was changed, if necessary, based on the Doppler
      results. RESULTS: Both clinical and Doppler examinations were equally effective
      in diagnosing primary varicose vein and identifying sites of venous incompetence.
      A family history for varicose veins was found in 21% and standing for a long
      period of time was a risk factor in 51% patients. The most common symptoms were
      pain and heaviness. Doppler study findings were useful in changing the management
      plan of 14 (15%) patients, 6 with recurrent varicose vein and 8 obese patients
      with chronic venous insufficiency. The majority of the patients (n = 82)
      benefited from surgery and were free of symptoms. CONCLUSION: This prospective
      study demonstrated that detailed clinical examination was sufficient to diagnose
      most patients suffering from primary varicose veins. Doppler vascular studies
      were useful in changing the treatment modality for those presenting with
      recurrent varicose vein or obese patients with signs and symptoms of chronic
      venous insufficiency with no clinically clear varicosity.

PMID- 14657620
TI  - The expression of rheumatoid arthritis in Kuwaiti patients in an outpatient
      hospital-based practice.
AB  - OBJECTIVE: To describe the characteristic clinical, serologic and radiological
      features of rheumatoid arthritis (RA) in Kuwaiti patients in a tertiary
      outpatient hospital-based practice. SUBJECTS AND METHODS: An outpatient hospital
      based study on 100 consecutive consenting Kuwaiti patients with RA was done at
      the Rheumatology Unit, Al-Amiri Hospital, one of the main teaching hospitals in
      Kuwait. The study group included 11 men and 89 women. The duration of their
      disease ranged from 2 to 30 years with a mean duration of 10.7 (SD 7.5) years.
      The age at disease onset ranged from 21 to 71 years with a mean age of 39.1 (SD
      11.2) years. RESULTS: Joints most commonly involved in RA were
      metacarpophalangeal, wrist, knee, and proximal interphalangeal joints. Extra
      articular manifestations were present in 24 patients; the most common was the
      sicca complex in 14 individuals. Rheumatoid factor seropositivity was found in 60
      patients and erosive arthropathy in 42 patients. CONCLUSION: The findings
      indicate a low incidence of radiological erosive arthropathy in Kuwaiti patients.
      The sicca complex was the most common extra-articular manifestation of RA in
      these patients.

PMID- 14657621
TI  - Aseptic leptomeningitis in systemic lupus erythematosus. A case report.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) with leptomeningeal involvement is
      a rare condition. We report a case in a 17-year-old woman. CLINICAL PRESENTATION
      AND INTERVENTION: The patient was admitted to hospital with the complaints of
      vertigo, nausea, vomiting, headache, diplopia, ptosis on the left and weakness of
      the left leg. A diagnosis of SLE was established, with diffuse leptomeningeal
      involvement demonstrated by cranial magnetic resonance imaging. When treated with
      steroids, the clinical problems resolved almost completely. CONCLUSIONS: Although
      rare, leptomeningeal involvement can complicate SLE. Cranial magnetic imaging can
      demonstrate tissue involvement. The condition responds to steroid therapy.

PMID- 14657622
TI  - Successful management of a widespread osteosarcoma. A case report.
AB  - OBJECTIVE AND IMPORTANCE: To report the case of a 23-year-old woman with
      widespread osteosarcoma including skeletal, pulmonary and pleural metastases, who
      had a remarkable response to combined chemo- and radiotherapy. CLINICAL
      PRESENTATION AND INTERVENTION: A 23-year-old Indonesian woman presented in
      October 1999 with a swelling of the right thigh, severe generalized pain and
      progressive left hemiparesis. Radiological examination revealed osteolytic
      lesions in the cervical spine. CT scan of the chest showed multiple pulmonary
      metastases and a huge left pleural effusion. Bone scan with technetium-99m
      hydroxymethylene diphosphonate showed intense uptake of the radiopharmaceutical
      in the distal right femur, generalized deposits throughout the skeleton and in
      the right hemithorax corresponding to the lung findings. Bone marrow and kidney
      function tests as well as serum calcium level were normal. Alkaline phosphatase
      was markedly elevated, 8,000 IU/l (normal <250 IU/l). Histopathology from the
      femoral tumor showed osteosarcoma. Treatment was started with radiotherapy to the
      cervical spine followed immediately by a combination chemotherapy with
      ifosfamide, cisplatin, etoposide and mesna rescue. In addition, the patient
      received bisphosphonates regularly. Eleven cycles of chemotherapy were given with
      a remarkable response. CONCLUSION: The patient was successfully treated with a
      combination of radio- and chemotherapy. She recovered fully and is in almost
      complete remission. The disease remained stable 24 months after the
      discontinuation of the treatment.

PMID- 14657623
TI  - Is androgenetic alopecia a photoaggravated dermatosis?
AB  - Progressive thinning of the scalp hair in androgenetic alopecia (AGA) results in
      a gradual decline in natural protection of the scalp from ultraviolet radiation
      (UVR). A number of pathologic conditions of the scalp are evidently related to
      UVR, particularly photosensitive diseases and disorders of the chronically
      photodamaged bald scalp. The most important chronic effects of UVR are
      photocarcinogenesis and solar elastosis. Besides these, erosive pustular
      dermatosis and 'red scalp' are distinct disorders peculiar to the balding scalp.
      While the consequences of sustained UVR on the unprotected scalp are well
      appreciated, the effects of UVR on hair loss have widely been ignored. However,
      clinical observations and theoretical considerations suggest that UVR may have
      negative effects: acute telogen effluvium from UVR has been described, and the
      production of porphyrins by Propionibacterium sp. in the pilosebaceous duct, with
      photoactivation of porphyrins leading to oxidative tissue injury, has been
      implicated in follicular microinflammation. Alternatively, keratinocytes
      themselves may respond to physicochemical stress from UVR, besides irritants and
      pollutants, by producing radical oxygen species and nitric oxide and by releasing
      proinflammatory cytokines, eventually leading to injury of the putative site of
      follicular stem cells in the superficial portion of the hair follicle. Since all
      of these processes involved in hair loss share the common feature that they are
      induced or exacerbated by exposure to sunlight, it is proposed that AGA is a
      photoaggravated dermatosis that requires photoprotection.

PMID- 14657624
TI  - Detection of herpes simplex virus genomic DNA in various subsets of Erythema
      multiforme by polymerase chain reaction.
AB  - BACKGROUND: The wide variation in the detection of herpes simplex virus (HSV) DNA
      (36-75%) by polymerase chain reaction (PCR) in erythema multiforme (EM) may be
      partly attributed to differences in case selection in terms of subsets of EM
      studied. OBJECTIVE: To determine the frequencies of detection of HSV DNA in
      specific subsets of EM. METHODS: Nested PCR was used to detect HSV DNA in skin
      biopsies with histologically proven EM. RESULTS: PCR was performed on skin
      biopsies from 63 patients with EM. HSV DNA was detected in 3/11 (27.2%) of single
      episode HSV-associated EM (HAEM), 6/10 (60%) of recurrent HAEM, 1/4 (25%) of
      single-episode idiopathic EM and 6/12 (50%) of recurrent idiopathic EM. HSV DNA
      was not detected in atypical EM (0/11), suspected drug-induced EM (0/9) or
      Stevens-Johnson syndrome (0/6). CONCLUSION: The overall PCR positive rates of
      HAEM (42.9%) and idiopathic EM (43.8%) were comparable suggesting that idiopathic
      EM is likely to be related to a subclinical HSV infection.

PMID- 14657625
TI  - Review of the chronology of clinical manifestations in 60 patients with Behcet's
      disease.
AB  - BACKGROUND: The natural course of Behcet's disease is not fully known. OBJECTIVE:
      The aim of the present study was to determine the occurrence of the symptoms
      retrospectively in chronologic order in patients with Behcet's disease, diagnosed
      according to the criteria of the International Study Group for Behcet's Disease.
      METHODS: A total of 60 consecutive patients (29 male and 31 female; aged 35.87 +/
      9.84 years) were involved in the study. The symptoms of the disease were
      retrospectively recorded in the time order of the manifestations per patient.
      RESULTS: Oral ulcer was the most commonly observed onset manifestation (51 of 60
      patients: 85%), followed by genital ulcer (13 of 60 patients: 21.7%) and
      articular symptoms (10 of 60 patients: 16.7%). The duration between the oral
      ulcer and the fulfillment of diagnostic criteria was calculated to be 3.77 +/-
      4.43 years. The same duration was 2.50 +/- 4.74 and 2.11 +/- 3.44 years for
      genital ulcer and articular symptoms, respectively. The duration between the time
      point of fulfillment of diagnostic criteria and the diagnosis (2.83 +/- 2.3
      years) was found to be longer in female patients (3.2 +/- 2.5 years). The
      duration was also longer in patients having only mucocutaneous lesions (3.18 +/-
      2.5 years) than in patients having serious organ involvement such as eye disease
      (1.63 +/- 0.7 years; p < 0.05). CONCLUSION: Our study indicates that oral ulcer
      is the onset manifestation in the majority of the patients and the disease is
      often diagnosed with a delay of several years after the appearance of the onset
      sign.

PMID- 14657626
TI  - Flow-cytometric DNA analysis in cutaneous fibrohistiocytic tumors.
AB  - BACKGROUND: Fibrohistiocytic tumors are rare skin tumors. There are many kinds of
      fibrohistiocytic tumors. It is often difficult to differentiate
      dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH)
      from dermatofibroma (DF) and other benign tumors. OBJECTIVE: In this study, the
      possible usefulness of DNA ploidy for the differentiation was studied. METHODS:
      Five MFH, 9 DFSP, 3 DF, 2 lipofibromas and 2 scars were studied for DNA ploidy
      using a flow cytometer. RESULTS: All the 7 benign tumors showed a diploid
      pattern. Of 14 malignant fibrohistiocytic tumors, 8 cases (57.1%) showed an
      aneuploid and 6 a diploid pattern. Two of 5 MFH (40.0%) and 6 of 9 DFSP (66.7%)
      showed an aneuploid pattern. These results showed that fibrohistiocytic tumors
      with an aneuploid pattern are malignant, though those with a diploid pattern may
      be benign or malignant. CONCLUSION: Analysis of DNA ploidy using flow cytometry
      was concluded to be useful for the differentiation of malignant fibrohistiocytic
      tumors from benign ones.

PMID- 14657627
TI  - Bacteria ingestion by blowfly larvae: an in vitro study.
AB  - BACKGROUND: Maggot debridement therapy is the medical use of live fly larvae for
      cleaning chronic and infected wounds, removing devitalized tissue and decreasing
      the risk of infection. Maggot-derived proteins are able to kill bacteria, and
      proteolytic enzymes are responsible for the liquefying of necrotic tissue.
      OBJECTIVE: The aim of this study is to investigate bacterial ingestion by larvae
      roaming free on bacterial agar, compared to those larvae contained within vinyl
      bags. METHODS: Free-roaming sterile larvae of Lucilla sericata and larvae
      contained in vinyl bags were fed on Escherichia coli producing green fluorescent
      protein (GFP). The time interval to the onset of fluorescent maggots was
      determined. At different time intervals, maggots were sacrificed, washed in
      sterile saline, sagittally cut in frozen sections and examined under a microscope
      with UV light. RESULTS: After feeding on GFP-labelled E. coli, maggots roaming
      free on bacterial lawn agar demonstrated fluorescence after 3 min, maggots
      entrapped in vinyl bags after 25 min. In the sagittal frozen sections, the
      highest fluorescent intensity was detected in the larvae's rostral part of the
      alimentary tract, the crop and the anterior midgut. CONCLUSION: In an in vitro
      setting, digestion and ingestion of whole or disintegrated bacteria is
      accomplished within minutes. The vinyl bag's permeable membrane clearly causes a
      delay of this process.

PMID- 14657628
TI  - Increased serum levels of tumor necrosis factor alpha in lichen planus.
AB  - BACKGROUND: Lichen planus (LP) is a common, pruritic, inflammatory mucocutaneous
      disease. There are several opinions and approaches to the etiopathogenesis of LP.
      Immunologic mechanisms almost certainly mediate its development. T-cell-mediated
      immunity plays the major role in triggering the clinical expression of the
      disease. The cytokines that are produced by lymphocytes also play an important
      role in the development of LP. OBJECTIVE: The goal of our study was to
      investigate the possible role of tumor necrosis factor alpha (TNF-alpha) in the
      pathogenesis of LP. METHODS: Serum TNF-alpha levels were determined with the
      enzyme-linked immunosorbent sandwich assay method in the sera of 40 patients
      suffering from LP and in those of 40 healthy controls. RESULTS: The serum levels
      of TNF-alpha were found to be significantly higher in the patient group compared
      to the healthy controls (patients: 35.64 +/- 9.59 pg/ml, controls: 15.6 +/- 3.97
      pg/ml, p < 0.001). CONCLUSION: Our results revealed that TNF-alpha might play a
      major role in the pathogenesis of LP.

PMID- 14657629
TI  - Lack of association between the promoter polymorphisms at positions -308 and -238
      of the tumor necrosis factor alpha gene and psoriasis vulgaris in Japanese
      patients.
AB  - BACKGROUND: Psoriasis features an increased level and activity of tumor necrosis
      factor alpha (TNF-alpha). The TNF-alpha gene has single nucleotide polymorphisms
      (SNPs) at positions -308 (-308G>A) and -238 (-238G>A) in the promoter region, and
      the -238G>A SNP has been reported to be associated with psoriasis vulgaris (PV)
      and psoriatic arthritis in Caucasians. OBJECTIVE: To examine whether these SNPs
      are associated with susceptibility to PV in Japanese patients, we investigated
      the genotype and allele frequencies at each SNP in Japanese PV patients and in
      controls. METHODS: We examined 163 PV patients and 96 healthy individuals.
      Genotyping was performed using the polymerase chain reaction-restriction fragment
      length polymorphism method. RESULTS: No significant association between the
      genotypes or alleles of these SNPs and susceptibility to PV was observed.
      CONCLUSION: These SNPs themselves are not associated with susceptibility to PV in
      the Japanese.

PMID- 14657630
TI  - Evaluation of in vitro resistance in patients with onychomycosis who fail
      antifungal therapy.
AB  - BACKGROUND: With the increased awareness of onychomycosis and the increasing use
      of antifungals for this indication, it is prudent to be concerned about the
      possible emergence of resistant strains. There has been substantial work on the
      development of standardized methods for testing the in vitro resistance of
      various fungi and yeasts to the currently available antifungal agents. However,
      relatively little research has been published concerning the resistance of
      dermatophyte species. OBJECTIVE: We report the results of a retrospective study
      analyzing the relationship between in vitro and clinical resistance in strains of
      Trichophyton rubrum cultured from patients with recalcitrant dermatophyte toe
      onychomycosis. MATERIALS AND METHODS: We analyzed the in vitro resistance of
      dermatophyte strains obtained from 18 patients with chronic onychomycosis who
      failed antifungal therapy with itraconazole or terbinafine. Multiple-sequential
      strains from 11 patients were included in the study. Susceptibility testing of
      these strains was performed against 4 antifungals, itraconazole, ketoconazole,
      terbinafine and ciclopirox, using the broth microdilution method as per the NCCLS
      M27-A guidelines. A record of clinical characteristics that may relate to patient
      treatment and therapy was maintained. RESULTS: All of the strains were
      susceptible to 3 of the 4 antifungal agents tested. Although there was no direct
      correlation between clinical resistance and in vitro resistance, increased
      minimum inhibitory concentration values for ketoconazole were observed in strains
      obtained after treatment from 3 of 18 patients evaluated in the study. In all but
      1 patient, we were able to identify other factors that may have been responsible
      for treatment failure. CONCLUSIONS: With the more common use of antifungals to
      treat various fungal infections, development of increased resistance in the
      causative organisms remains a possibility. However, factors other than fungal
      resistance may also be implicated in treatment failure.

PMID- 14657631
TI  - Topical tacrolimus as a therapeutic adjunct in patients with cutaneous lupus
      erythematosus. A report of three cases.
AB  - The topical therapy of cutaneous lupus erythematosus (LE) consists mainly of
      corticosteroids which may lead to significant side effects when overused. We
      report the efficacy of topical tacrolimus as a therapeutic adjunct in 3 patients
      with cutaneous LE of the face. All patients, 1 with systemic LE and a malar rash,
      1 with annular subacute cutaneous LE, the other with a papular variant of
      subacute cutaneous LE, experienced significant improvement following application
      of tacrolimus ointment. Treatment with topical tacrolimus was tolerated well
      without major side effects in all patients. The presented cases are in line with
      recent reports that topical tacrolimus may be effective in facial LE.

PMID- 14657633
TI  - Acquired perforating dermatosis in a patient with Poland syndrome.
AB  - Acquired perforating dermatosis (APD) is characterized by umbilicated 1- to 10-mm
      measuring papulonodules with a central adherent oystershell-like keratotic plug,
      typically on the dorsa of the hands, forearms and over the knees. APD is
      associated with systemic diseases, especially diabetes mellitus and/or renal
      failure. Histologically the lesions show transepidermal elimination of altered
      dermal components into a cup-shaped epidermal depression. We present a 69-year
      old man with coexisting APD and Poland syndrome (PS), an association not yet
      described. PS (OMIM 173800) is a rare congenital anomaly consisting of unilateral
      partial or total absence of the greater pectoralis muscle and ipsilateral
      symbrachydactyly. Most cases of PS are sporadic as it was in our case. Our
      patient had, in addition, an untreated diabetic condition, hyperuricaemia,
      dilated cardiomyopathy and a very recent pulmonary embolism. He responded to
      therapy with allopurinol.

PMID- 14657632
TI  - Erythema multiforme-like drug eruption with oral involvement after intake of
      leflunomide.
AB  - Leflunomide is an antirheumatic agent of the type of a 'disease-modifying
      antirheumatic drug'. In rare cases, severe skin reactions up to the extreme
      expression of toxic epidermal necrolysis have been observed. A female patient
      with rheumatoid arthritis had been treated with systemic steroids and
      methotrexate for 2 years. Five weeks prior to admission to our hospital
      methotrexate was replaced by leflunomide. Three weeks after initiation of
      leflunomide therapy a progressive generalized erythema with blistering formation
      occurred accompanied by increase of body temperature, chills and erosive lesions
      on the lips and oral mucosa. The palmar and plantar surfaces revealed edema,
      erythema and pulpitis with epidermolysis. On histologic examination necrotic
      keratinocytes and epidermal spongiosis were observed. After administration of
      high-dose prednisolone and topical treatment the patient recovered within 14
      days. This is one of the few cases of severe drug reaction after intake of
      leflunomide. Therefore, the indication of this relatively new drug should be
      considered carefully.

PMID- 14657634
TI  - Microcystic adnexal carcinoma with lymph node metastasis.
AB  - Microcystic adnexal carcinoma (MAC) affects predominantly the face and seldom
      metastasizes. We report a case occurring in the axilla of a 63-year-old male.
      Histology revealed the characteristic features of MAC. Eleven months after the
      excision, he underwent a reexcision with wide margins because of local
      recurrence. Histologically, the central area of the recurrent lesion revealed the
      typical histologic features of MAC, and the periphery showed a proliferation of
      irregular duct-like and glandular structures with a mixed pattern. Two lymph
      nodes that were not adherent to the tumor had metastatic tumor cells. The present
      case confirms that MAC can metastasize, although it may also be hypothesized that
      the recurrent lesion represented transformation into a higher-grade carcinoma.

PMID- 14657635
TI  - Increased expression of VEGF in glomeruloid reactive angioendotheliomatosis.
AB  - Reactive angioendotheliomatosis (RAE) is a very rare disorder characterized by
      marked proliferation of endothelial cells. It is often associated with
      infections, such as subacute bacterial endocarditis, but has also been described
      as an early sign of a developing hematological malignancy. We report the case of
      a 71-year-old Caucasian female who developed lupus-like RAE lesions. A thorough
      diagnostic workup and subsequent 3-year clinical follow-up revealed no sign of an
      underlying infectious or neoplastic disorder. Repetitive serum immunofixations
      were only once consistent with a monoclonal gammopathy of undetermined
      significance. In lesional skin, the pronounced bud-like endothelial cell
      formation was associated with an increased epidermal expression of vascular
      endothelial growth factor (VEGF), a potent angiogenic mediator. In accordance
      with the paracrine action of epidermally derived VEGF, vascular endothelial cells
      in lesional skin revealed increased expression of the VEGF receptor VEGFR-2
      (KDR). This case suggests a possible role of epidermally derived VEGF in
      endothelial cell proliferation in RAE.

PMID- 14657636
TI  - Eruptive large melanocytic nevus in a patient with hereditary epidermolysis
      bullosa simplex.
AB  - Hereditary epidermolysis bullosa (HEB) is a group of genetically determined
      mechanobullous disorders characterized by blister formation following minor
      trauma. Unusual melanocytic lesions may be a rare feature of all major categories
      of HEB. We report a large melanocytic nevus, clinically simulating malignant
      melanoma, which developed at a site of healing blisters in an 8-year-old male
      with recessive generalized epidermolysis bullosa simplex (EBS). Histological
      findings were consistent with a compound nevus. This is the third reported case
      of an eruptive melanocytic nevus developing in EBS. Due to their unique features,
      it has been suggested that these nevi may represent a distinct variant, referred
      to as epidermolysis bullosa nevi. Despite the atypical picture, no malignant
      transformation of HEB nevi has been seen. Therefore, after histologic
      verification, regular long-term follow-up rather than radical surgery is
      recommended.

PMID- 14657637
TI  - Progressive macular hemangioma: a new entity?
AB  - We report a 22-year-old man with an extensive cutaneous vascular lesion involving
      the left arm since the age of 2 months. The lesion was macular and had been
      growing steadily in extent since its appearance. It had crossed the midline in
      several places. There was no involvement of any internal organ. Histopathology
      and immunostaining revealed unmistakable evidence of vascular proliferation. The
      predominantly macular character of the lesion, even with passage of time, besides
      the absence of several other features, usually associated with a tufted angioma,
      led us to the use of the term 'progressive macular hemangioma' for this
      condition.

PMID- 14657638
TI  - Childhood capillary hemangioma presenting as infantile perianal protrusion.

PMID- 14657639
TI  - Successful treatment of intractable scleromyxedema with cyclosporin A.

PMID- 14657640
TI  - Association of granzyme-B-positive lymphocytes in regressing plane warts.

PMID- 14657641
TI  - Phacomatosis pigmentokeratotica without extracutaneous abnormalities.

PMID- 14657642
TI  - Acute urticaria and angioedema due to ehrlichiosis.

PMID- 14657643
TI  - Analysis of T-cell receptor gamma gene rearrangements by PCR-Genescan and PCR
      polyacrylamide gel electrophoresis in early-stage mycosis fungoides/large-plaque
      parapsoriasis.

PMID- 14657644
TI  - Generalised annular elastolytic giant cell granuloma.

PMID- 14657645
TI  - Clearance of necrobiosis lipoidica with fumaric acid esters.

PMID- 14657646
TI  - A case of eruptive infundibulomas.

PMID- 14657647
TI  - The close association of Lymphadenitis tuberculosa and Erythema induratum of
      Bazin in Japanese patients.

PMID- 14657648
TI  - Failure of prolonged extracorporeal photopheresis in the treatment of alopecia
      areata universalis in two patients.

PMID- 14657649
TI  - Dermoscopy of clear-cell acanthoma differs from dermoscopy of psoriasis.

PMID- 14657652
TI  - A role for JNK-paxillin signaling in cell migration.
AB  - Recently, we and others demonstrated that JNK is essential for cell migration in
      a number of cell types. We also showed that JNK phosphorylates serine 178 on
      paxillin, a focal adhesion adaptor, both in vitro and in vivo. Moreover,
      phosphorylation of Ser 178 on paxillin is essential for cell migration and
      involved in modulating cell adhesions. A model is proposed to depict the role of
      JNK-paxillin signaling in cell migration.

PMID- 14657653
TI  - Bcl-2 in cell cycle regulation.

PMID- 14657654
TI  - Early growth response-1: blocking angiogenesis by shooting the messenger.
AB  - Early growth response-1 (Egr-1) is an immediate early gene, which encodes a zinc
      finger transcription factor. Recent evidence indicates that Egr-1 plays a crucial
      role in angiogenesis, the formation of new blood vessels from the pre-existing
      vasculature. DNAzymes (catalytic single-stranded DNA) targeting the Egr-1 mRNA
      inhibit Egr-1 and FGF-2 expression, block endothelial cell growth, and suppress
      neovascularization and tumor angiogenesis in various animal models.

PMID- 14657655
TI  - Lkb1 and GSK3-beta: kinases at the center and poles of the action.

PMID- 14657656
TI  - How to activate a damage-tolerant polymerase: consequences of PCNA modifications
      by ubiquitin and SUMO.

PMID- 14657657
TI  - Replication initiation in mammalian cells: changing preferences.
AB  - Accurate duplication of genetic material is central to cell proliferation. In
      eukaryotes, S phase is tightly controlled during development. For example,
      initiation events occur at random sites in early embryos but later appear
      restricted to preferred DNA regions. Epigenetic changes depending on chromatin
      organization and/or availability of specific factors likely control origin
      choice. By using the dynamic molecular combing technology, coupled with specific
      labeling of neo-synthesized DNA and FISH, we recently demonstrated that the
      efficiency and spacing of initiation sites are still flexible in mammalian
      somatic cells, and strongly rely on nucleotide availability. In all conditions,
      initiation events appear confined to short AT-rich sequences previously
      identified as matrix attachment regions, which suggests a direct involvement of
      these features in origin specification. Functional relationships between matrix
      anchorage and origin selection are discussed.

PMID- 14657659
TI  - Chromosome shaping by two condensins.
AB  - It remains a big challenge in modern cell biology to determine the mechanism by
      which a discrete set of rod-shaped chromosomes is assembled from an amorphous
      mass of interphase chromatin. Recent studies start to shed new lights on how this
      process is actively supported by a class of multiprotein complexes called
      condensins. In vertebrate cells, two different condensin complexes make distinct
      mechanistic contributions to determining the shape and integrity of mitotic
      chromosomes.

PMID- 14657658
TI  - Functional link between Myc and the Werner gene in tumorigenesis.
AB  - We have recently reported a connection between the expression of the Werner
      syndrome gene (WRN), whose loss of function has been implicated in a human
      progeroid syndrome (WS), and the Myc oncoprotein. Myc overexpression directly
      elevates trancription of the WRN gene, whose presence is required to avoid
      senescence during Myc proliferative stimuli. Here we discuss several hypotheses
      to explain why WRN might be required to support oncogenic proliferation in light
      of the known function of WRNprotein and Myc in genomic instability and
      transcriptional modulation. In addition, we address the apparent paradox of why
      patients with WS, lacking WRN function, have increased incidence of certain
      cancers.

PMID- 14657660
TI  - Gene expression sigantures, cancer cell evolution and metastatic progression.
AB  - Global gene expression profiling and molecular cytogenetics for single cells
      provide new opportunities to resolve important questions, such as the mechanisms
      of tumor cell selection during cancer progression. While gene expression analyses
      show that metastatic progression correlates with the deregulation of certain gene
      sets in the primary tumor, the direct analysis of disseminated cancer cells, the
      putative precursors of metachronous metastases, suggests that dissemination is a
      very early event in the genetic development of human cancers.

PMID- 14657661
TI  - Cycling without cyclins.
AB  - Complex oscillations in the activation and inactivation of cyclin-dependent
      kinase complexes propel mammalian cells through the cycle. A recent spate of
      studies seems to indicate that many, if not most, of these seemingly essential
      molecules may, in some senses, be dispensable. If true, that would mean the
      essential components of the mammalian cell cycle are not much different from
      those found in prokaryotes. That, in turn, would imply a fair amount redundancy
      exists in the system which may call into question current cancer treatment
      strategies designed to target some of these "dispensable" cell cycle control
      molecules.

PMID- 14657662
TI  - Cdk2 as a master of S phase entry: fact or fake?
AB  - It has long been believed that Cdk2 and its activator cyclin E play essential
      roles in the progression of the mitotic cell cycle. However, recent studies using
      knockout mouse models revealed that neither Cdk2 nor cyclin E are essential in
      vivo. The purpose of this Perspective is to compare both Cdk2 and cyclin E
      knockout mice models and to discuss potential mechanisms driving the cell cycle
      in the absence of Cdk2 or cyclin E. Particular emphasis is placed on possible non
      catalytic roles of cyclin E, the expression and activity of the second cyclin
      binding partner of Cdk2, cyclin A, as well as on the expression and degradation
      of the Cdk2 inhibitor p27Kip1 in the absence of Cdk2.

PMID- 14657663
TI  - Drosophila invasive tumors: a model for understanding metastasis.
AB  - Inactivation of Drosophila tumor suppressor genes can cause excessive
      proliferation and, in some cases, neoplastic growth. Neoplastic growth in
      Drosophila tissues can also be followed by metastasis upon transplantation into
      hosts or in vivo. Recently, we have shown that metastatic tumors of Drosophila
      can provide a model in which to identify genes that are involved in the
      metastatic process.

PMID- 14657664
TI  - Many fingers on the mitotic trigger: post-translational regulation of the Cdc25C
      phosphatase.
AB  - The mitotic inducer Cdc25 phosphatase controls the activation of Cdc2/cyclin B
      protein kinase and entry into mitosis in eukaryotic cells. Cdc25C is highly
      regulated by multiple post-translational modifications within its N-terminal
      regulatory domain and site-specific protein interactions. Phosphorylation of one
      inhibitory site targeted by multiple kinases determines the timing of Cdc25C
      activation and arrests cells in G2 in response to checkpoint, stress,
      developmental and extracellular signals. In mitosis, phosphorylation of several
      Ser/Thr residues and Pin1-catalysed peptidyl-proline isomerisation produces
      activation. Phosphorylation of one activating site is antagonistic to the
      proximal inhibitory site and maintains Cdc25C activity during mitosis.
      Phosphorylation and interacting proteins also modulate the nuclear import and
      export signals on Cdc25C, inducing dramatic changes in its localisation within
      the cell. Thus, the regulation of Cdc25C activity and localization integrates
      multiple signals that govern the decision to enter mitosis.

PMID- 14657665
TI  - Cell cycle checkpoint proteins and cellular response to treatment by anticancer
      agents.
AB  - The response of cancer cells to treatment with anticancer agents is mediated in
      part by proteins controlling both the cell cycle progression and the genomic
      integrity, including p53, p73 and checkpoint proteins chk1 and chk2. We here
      summarized the cellular functions of these proteins, their alterations in human
      tumors and the impact of their mutations/alterations on cellular response to
      treatment, Particular attention has been paid for those studies performed in
      isogenic cell systems, to minimize as much as possible interference by other
      alterations invariably present when different cell types are considered. Focus
      has also be given to the approaches taken to exploit the differential expression
      of these proteins between normal and tumor cells to improve the selectivity of
      treatment with anticancer agents.

PMID- 14657666
TI  - The achilles heel of ErbB-2/HER2: regulation by the Hsp90 chaperone machine and
      potential for pharmacological intervention.
AB  - Signal transduction mediated by ErbB/HER receptor tyrosine kinases is crucial for
      the development and maintenance of epithelial tissues, and aberrant signaling is
      frequently associated with malignancies of epithelial origin. This review focuses
      on the roles played by the Hsp90 chaperone machinery in the regulation of
      signaling through the ErbB/HER network, and discusses potential therapeutic
      strategies that disrupt chaperone functions. Hsp90 and its associated
      cochaperones regulate ErbB signal transduction through multiple mechanisms. The
      chaperone system controls the stability of the nascent forms of both ErbB-1 (EGF
      receptor) and ErbB-2/HER2, while regulation of the mature form is restricted to
      ErbB-2. Regulation by the Hsp90 complex extends to downstream effectors of ErbB
      signaling, namely Raf-1, Pdk-1 and Akt/PKB. Disrupting the function of Hsp90
      results in the degradation of both the receptors and their effectors, thereby
      inhibiting tumor cell growth. The importance of an Hsp90-recognition motif
      located within the kinase domain of ErbB-2 is discussed, as well as a direct role
      for Hsp90 in regulating tyrosine kinase activity. In light of recent
      observations, we emphasize the ability of specific tyrosine kinase inhibitors to
      selectively target ErbB-2 to the chaperone-mediated degradation pathway. ErbB
      specific drugs are already used to treat cancers, and clinical trials are
      underway for additional compounds that intercept ErbB signaling, including drugs
      that target Hsp90. Hence, the dependence of ErbB-2 upon Hsp90 reveals an Achilles
      heel, which opens a window of opportunity for combating cancers driven by the
      ErbB/HER signaling network.

PMID- 14657667
TI  - Why do cells require heat shock proteins to survive heat stress?
AB  - The cellular response to heat stress includes the induction of a group of
      proteins called the Heat Shock Proteins, whose functions include the synthesis of
      the thermoprotectant trehalose, refolding of denatured proteins, and ubiquitin-
      and proteasome-dependent degradation. Recent studies show that simply increasing
      the activity of ubiquitin- and proteasome-dependent degradation can replace the
      essential functions played by the induction of heat shock proteins during a heat
      stress. These results suggest that accumulation of denatured or aggregated
      proteins is the reason for the loss of cell viability due to heat stress.

PMID- 14657668
TI  - Apoptosis, necrosis and between.

PMID- 14657669
TI  - Inhibition of phosphatidylinositol 3-kinase causes apoptosis in retinoic acid
      differentiated hl-60 leukemia cells.
AB  - Phosphatidylinositol 3-kinase (PI3-K) signaling may inhibit apoptosis in
      neoplastic cells. The PI-3K inhibitor wortmannin renders cells apoptosis-prone.
      Inducers of differentiation may also cause apoptosis. To detect the effect of
      wortmannin on the survival of differentiated human acute promyeloid leukemia
      cells, HL-60 cells were induced to differentiation with treatment of all trans
      retinoic acid (ATRA) followed by treatment with wortmannin. Results showed that
      apoptosis occurred in cells that underwent differentiation, but not in
      undifferentiated HL-60 cells. The pro-apoptotic molecule, Bad, played a role in
      this apoptotic mechanism. Thus, the survival of differentiated HL-60 cells
      induced by ATRA depends on the ability of the PI3-K pathway to transduce survival
      signals; the PI3-K inhibitor, wortmannin, can induce apoptosis of differentiated
      HL-60 cells. These results may indicate a novel method for treating cancer with
      differentiation induction and signal pathway regulation.

PMID- 14657670
TI  - PAK is essential for RAS-induced upregulation of cyclin D1 during the G1 to S
      transition.
AB  - Oncogenic RAS mutants such as v-Ha-RAS induce cell cycling, in particular the G1
      to S transition, by upregulating cyclin D1 and downregulating p27, an inhibitor
      for cyclin-dependent kinases (CDKs). PI-3 kinase appears to be involved in the
      regulation of both cyclin D1 and p27. In this report, using two distinct
      inhibitors specific for PAK1-3 (CEP-1347 and WR-PAK18), we present the first
      evidence indicating that the PIX/Rac/CDC42-dependent Ser/Thr kinases PAK1-3,
      acting downstream of PI-3 kinase and upstream of the Raf/MEK/ERKs kinase cascade,
      is essential for RAS-induced upregulation of cyclin D1, but not downregulation of
      p27. Since these PAK-inhibitors block selectively the malignant growth of RAS
      transformants, in which PAK1 is constitutively activated, but not normal cell
      growth, it is suggested that RAS transformants are addicted to the high levels of
      PAK1 for their malignant entry to S phase.

PMID- 14657671
TI  - Codon-optimized cloning, expression and characertization of the C-terminal region
      of human apoptotic protein GADD34 in Escherichia coli.
AB  - The human GADD34 (Growth Arrest and DNA Damage-inducible 34) is the product of an
      apoptosis- and DNA-damage-inducible gene. The C-terminus domain of GADD34 is
      highly homologous to HSV-1 gamma-1 34.5, HSV-2 and the African swine fever virus
      virulence-associated factor NL-S. Among these viral proteins, HSV-1 gamma 34.5
      protein is known to prevent apoptosis of viral-infected cells. Because of the
      difficulty in expressing GADD34 protein or any of its fragments, including the C
      terminus (amino acids 533-632) in E. coli, partially due to sub-optimal
      expression of eukaryotic codons in prokaryotic E. coli, we used a codon-optimized
      cloning scheme to construct the eukaryotic gene that codes for GADD34(533-632).
      We derived a novel PCR protocol to assemble 20 oligonucleotides into the
      synthetic GADD34(533-632) gene. The clear advantage of using this protocol is
      that the assembled gene is without the mutation and deletion that are usually of
      a major problem in constructing synthetic genes. The synthetic GADD34(533-632)
      gene was cloned, expressed, and purified in large quantity. We obtained
      approximately 50 mg of GADD34(533-632) protein per liter minimum-medium culture.
      To our knowledge, this is the first report of a large-scale production of the C
      terminus of GADD34. The production and purification of GADD34(533-632) in large
      quantity are essential for structure determination as well as for understanding
      its interactions with other proteins such as phosphatase 1-alpha using NMR
      spectroscopy and other biophysical methods.

PMID- 14657672
TI  - The development of a CDK2-docking site peptide that inhibits p53 and sensitizes
      cells to death.
AB  - Cyclin-dependent protein kinases play important roles in cell cycle progression
      and are attractive targets for the design of anti-proliferative drugs. Two
      distinct synthetic CDK1/2 inhibitors, Roscovitine and NU2058, are
      pharmacologically distinct in their ability to modify p53-dependent transcription
      and perturb cell cycle progression. Although such active-site CDK1/2 inhibitors
      comprise the most standard type of enzyme inhibitor, many protein kinases are
      proving to harbour high affinity docking sites that may provide a potentially
      novel interface for the design of kinase-inhibitors. We examined whether CDK2 has
      a docking site for its oligomeric substrate p53, whether small-peptide leads can
      be developed that inhibit CDK2 function, and whether such peptide-inhibitors are
      pharmacologically distinct from Roscovitine or NU2058. A docking site for CDK2
      was identified in the tetramerization domain of p53 at a site that is distinct
      from the phospho-acceptor site. Peptides derived from the tetramerization domain
      of p53 block CDK2 phosphorylation and identification of critical CDK2 contacts in
      the tetramerization domain of p53 suggest that kinase docking does not require
      tetramerization of the substrate. Transient transfection assays were developed to
      show that the GFP-CDK2 docking site fusion protein (GFP-CIP) attenuates p53
      activity in vivo and suppresses p21WAF1 induction which is similar to NU2058 but
      distinct from Roscovitine. A stable cell line with an inducible GFP-CIP gene
      attenuates p53 activity and induces significant cell death in a drug-resistant
      melanoma cell line, sensitizes cells to death induced by Doxorubicin, and
      suppresses cell growth in a colony formation assay. These data indicate that
      CDK2, in addition to cyclin A, can have a high affinity docking site for a
      substrate and highlights the possibility that CDK2 docking sites may represent
      effective targets for inhibitor design.

PMID- 14657673
TI  - Tolerance comes of age. Editorial comment.

PMID- 14657674
TI  - 'Actively acquired tolerance' of foreign cells. 1953.

PMID- 14657675
TI  - Vegetative hybridization of animals by joint blood circulation during embryonal
      development. 1953.

PMID- 14657676
TI  - The 50th anniversary of tolerance.

PMID- 14657677
TI  - Commentary on the "birth" of immunologic tolerance half a century ago.

PMID- 14657678
TI  - International rapprochement, 50 years ago.

PMID- 14657679
TI  - Comments from the translator of Hasek's article.

PMID- 14657680
TI  - Postoperative oral glucose tolerance and stimulated insulin secretion: a
      predictor of endocrine graft function more than 10 years after pancreas-kidney
      transplantation.
AB  - BACKGROUND: After pancreas transplantation, endocrine function is determined by
      the insulin secretory capacity of the transplanted pancreas. The authors
      evaluated the predictive value of postoperative oral glucose tolerance test
      (OGTT) and stimulated insulin secretion on long-term endocrine function. METHODS:
      Forty-one patients after pancreas-kidney transplantation with systemic venous
      drainage were studied. Patients were categorized to have normal glucose tolerance
      (NGT) or impaired glucose tolerance (IGT) (World Health Organization criteria:
      NGT, <7.8 mM; IGT, 7.8-11.1 mM 120 min after glucose intake) and high or low
      total insulin secretion. Mean follow-up of graft function and patient outcome was
      10.2+/-0.5 years after OGTT. RESULTS: Patients with IGT had grafts with a longer
      ischemia time and a significantly worse urine amylase excretion as compared with
      patients with NGT. Using Kaplan-Meier survival analysis, patients with NGT had
      better long-term pancreatic function as compared with IGT in the follow-up after
      performing the first OGTT (mean, 10.9+/-0.2 vs. 8.8+/-0.9 years of graft
      function; P=0.02), but there was no difference in patient survival and kidney
      graft function. Also, high insulin secretion predicted significantly longer
      pancreas graft function as compared with low insulin secretion (P=0.04).
      CONCLUSIONS: Although IGT does not lead to poorer long-term patient survival and
      kidney graft function, it does predict compromised long-term endocrine function
      of the transplanted pancreas. Therefore, postoperative OGTT are useful tools for
      identification of patients at risk of long-term endocrine graft failure after
      pancreas transplantation.

PMID- 14657681
TI  - Survival transplantation of preserved non-heart-beating donor rat livers:
      preservation by hypothermic machine perfusion.
AB  - BACKGROUND: Non-heart-beating donor (NHBD) livers are an untapped source with the
      potential to provide relief to the current donor shortage problem. Hypothermic
      machine perfusion (MP) has the potential to reclaim and preserve these marginal
      donor organs. METHODS: This study compared 5-day survival in a rat NHBD liver
      transplantation model with simple cold storage (SCS) and MP-preserved tissues
      that had experienced 30 min of warm ischemia followed by a 5-hr preservation
      period with the University of Wisconsin solution. Total release of lactate
      dehydrogenase (LDH) and alanine aminotransferase (ALT) were determined at major
      time points. Bilirubin levels and histology were examined after 5-day survival.
      RESULTS: Six of seven control livers and five of six MP livers survived, whereas
      SCS tissues had survival in zero of seven. The results showed that MP livers had
      reduced release of LDH and ALT after 5 hr of storage, 5.07+/-1.42 and 2.02+/-0.69
      U (mean+/-SE), respectively, compared with SCS, 15.54+/-0.81 and 3.41.3+/-0.73 U,
      respectively. Bilirubin values after 5-day survival of MP livers (1.17+/-0.49
      mg/dL) were comparable to controls (0.91+/-0.36 mg/dL). Histology confirms that
      SCS displayed increased necrosis and MP tissue showed regions of near normal
      hepatic structure. CONCLUSIONS: These results suggest that MP for 5 hr improves
      survival and reduces cellular damage of liver tissue that has experienced 30 min
      of warm ischemia when compared with SCS tissues. Further studies need to be
      conducted, but this study suggests that MP preservation has the potential to
      reclaim and preserve NHBD liver tissues.

PMID- 14657682
TI  - They talk the talk: Surveying attitudes and judging behavior about living
      anonymous kidney donation.
AB  - BACKGROUND: Over the past 30 years, numerous studies have reported that some
      individuals are willing to donate a kidney anonymously to a stranger; however,
      intentions are poor predictors of behavior. We surveyed individuals interested in
      being living anonymous donors (LADs), exposed them to an interview paralleling
      live-donor assessment, and measured their LAD commitment. Personality and
      donation decision factors were examined to corroborate cases of attitudinal and
      behavioral congruency. METHODS: A telephone survey of 1,002 randomly selected
      adults living in Vancouver, British Columbia, asked respondents how willing they
      were to donate a kidney, while alive, to particular individuals including a
      stranger. A subsample participated in a follow-up, which involved completing a
      mailed questionnaire and taking part in an in-depth interview. Expert raters
      judged respondents' commitment to being a LAD on the basis of the interviews.
      RESULTS: Two hundred fifty-eight (26%) of those surveyed stated they would
      probably or definitely be willing to donate a kidney to a stranger. Fifty-two
      completed the follow-up. Sixteen of the 52 (31%) were judged to be "committed
      LADs." No demographic differences were found between the committed LADs and the
      33 remaining "noncommitted participants." The committed LADs differed
      significantly from the noncommitted participants on personality measures and
      donation decision factors. These differences underscore the latter group's
      anonymous donation commitment. CONCLUSIONS: This study brings into focus the
      potential for a significant number of individuals coming forward as potential LAD
      candidates if they are informed about the need and given unbiased information
      about the procedure. We believe there is ethical latitude in allowing the
      promotion of LAD donation by interested third parties such as patient advocacy
      groups and professional bodies. We advocate public awareness of LAD programs as a
      first step followed thereafter by more provocative measures to engage the public
      in this endeavor.

PMID- 14657683
TI  - Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in
      complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell
      crossmatch-positive patients.
AB  - BACKGROUND: The aim of this study was to investigate the effect of Thymoglobulin
      and intravenous immunoglobulin (i.v.IG) therapy on the clinical outcome of a
      putatively high-risk group of kidney transplant recipients who have positive B
      cell complement-dependent cytotoxicity (CDC) along with positive T- or B-cell
      flow cytometry (FC) crossmatch results. METHODS: We prospectively studied the
      effects of i.v.IG and Thymoglobulin induction treatment in B-cell CDC, and T- or
      B-cell FC crossmatch-positive kidney transplant recipients (seven women and one
      man; mean age, 43+/-12 years). RESULTS: Mean peak panel-reactive antibody (PRA)
      was 47+/-32. Three patients had donor-specific antibody by flow PRA (two anti-DR4
      and one anti-A2). Each recipient received induction treatment with i.v.IG 100
      mg/kg for 3 days and Thymoglobulin 1.5 mg/kg for 5 days after transplantation. No
      acute cellular rejections occurred during a median follow-up of 15 months (range,
      12-17 months). Only one acute humoral rejection occurred 8 days after
      transplantation, which responded to plasmapheresis, i.v.IG, and rituximab. One
      allograft was lost because of polyoma nephritis. Patient survival was 100% and
      allograft survival was 88%. CONCLUSION: Our results indicate that i.v.IG and
      Thymoglobulin induction treatment may facilitate kidney transplantation in B-cell
      CDC and T- or B-cell FC crossmatch-positive patients.

PMID- 14657684
TI  - Incidence of cancer after kidney transplant: results from the North Italy
      transplant program.
AB  - BACKGROUND: Patients undergoing kidney transplantation demonstrate a higher risk
      of developing cancer as the result of immunosuppressive treatment and concurrent
      infections. METHODS: The incidence of cancer in a cohort of patients who
      underwent kidney transplantation between 1990 and 2000, and who survived the
      acute phase (10 days), was analyzed as part of the North Italy Transplant
      program. RESULTS: A total of 3,521 patients underwent transplantation during a 10
      year period in 10 of 13 participating centers; the length of follow-up after
      kidney transplant was 67.7+/-36.0 months. During the follow-up, 172 patients
      developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases,
      and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10
      colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The
      average time to cancer development after transplant was 40.1+/-33.4 months (range
      0-134 months). Twenty-four patients developed cancer within 6 months from the
      transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with
      lymphoproliferative diseases). Three patients demonstrated a second primary
      cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01
      per year. Independent determinants of cancer development were age, gender, and
      immunosuppressive protocol including induction. Ten-year mortality was
      significantly higher in patients with cancer (33.1%) than among patients without
      cancer (5.3%). The relative risk of death in subjects with cancer was 5.5
      (confidence interval 4.1-7.4). CONCLUSIONS: These preliminary data underline the
      importance of long-term surveillance of transplant recipients, choice of
      immunosuppressive treatment, and careful donor selection.

PMID- 14657685
TI  - Frequency and severity of acute rejection in live- versus cadaveric-donor renal
      transplants.
AB  - BACKGROUND: Live donors are an increasingly important source of kidneys for
      transplantation in Australia. The aim of this study was to compare the rate and
      severity of rejection between patients receiving kidney transplants from live
      versus cadaveric donors. METHODS: A retrospective analysis was undertaken of all
      patients receiving live-donor (n=109) and cadaveric-donor (n=389) renal
      transplants at our institution between April 1, 1994, and March 31, 2000. Follow
      up was completed on all patients until graft loss, death, or May 31, 2001.
      RESULTS: The baseline characteristics of the live-donor and cadaveric groups were
      similar, except for recipient age (mean+/-SD, 36.3+/-15.6 vs. 44.5+/-14.4 years,
      respectively; P<0.001); donor age (46.1+/-11.3 vs. 36.1+/-16.4 years, P<0.001);
      pretransplant dialysis duration (1.36+/-2.1 vs. 3.4+/-4.4 years, P<0.001); and
      the proportions of patients receiving first allografts (95% vs. 88%,
      respectively; P<0.05), antibody induction (8% vs. 20%, P<0.01), and mycophenolate
      mofetil (MMF) (60% vs. 37%, P<0.001). Acute rejection was observed in 48 (44%)
      live-donor and 108 (28%) cadaveric transplants (P=0.001). Cadaveric donor type
      was independently predictive of less acute rejection both on logistic regression
      (adjusted odds ratio [AOR], 0.47; 95% confidence interval [CI], 0.30-0.73;
      P=0.001) and multivariate Cox proportional hazards model analysis (hazard ratio,
      0.49; 95% CI, 0.34-0.69; P<0.001). Patients receiving cadaveric-donor transplants
      were also significantly less likely to receive antibody therapy for rejection
      (univariate, 18% vs. 9%; P=0.006; multivariate AOR, 0.45; 95% CI, -0.25-0.82;
      P<0.01), independent of recipient age, gender, race, transplant number, human
      leukocyte antigen mismatch, sensitization, induction therapy, delayed graft
      function, MMF use, tacrolimus or cyclosporine A use, sirolimus-everolimus use,
      year of transplant, donor age, or dialysis duration. However, donor type did not
      independently influence graft survival, immunologic graft survival, or patient
      survival. CONCLUSIONS: Live-donor kidney transplant recipients had a higher rate
      and severity of rejection and a shorter rejection-free period than cadaveric
      renal transplant recipients. Further consideration of the reasons for this
      difference and the use of alternative immunosuppressive strategies for live-donor
      transplants are recommended.

PMID- 14657687
TI  - Psychological consultation before living kidney donation: finding out and
      handling problem cases.
AB  - BACKGROUND: Since 1996, a team of medical psychologists, nephrologists, and
      urologists at Heidelberg University Hospital has developed a family-oriented
      consultation procedure for donors, recipients, and family members before living
      kidney transplantation. Qualitative content analyses of these consultations and
      their follow-up histories are presented, with particular focus on "problem
      cases." METHODS: Sixty-seven consultation interviews were explored by rating
      family interaction, consultee-consultant interaction, decision-making process,
      and intervention strategies in problem cases. Subsequently, 33 catamnestic
      interviews 1 year or more after living donation were explored by qualitative
      content analysis for donor and recipient quality of life, quality of
      relationships, and health status. RESULTS: Generally, donors show themselves to
      be eager; recipients appear more reluctant. Expectations focus on spontaneity and
      a "normal life." Fears are usually expressed not about oneself but about the
      partner involved. Types of confrontation with possible complications are anxious
      avoidance, active consideration, and optimistic fatalism. Past family experiences
      of medical traumata may influence content and level of anxiety. Problem cases are
      characterized by unilaterally dependent close relationships, unrealistic
      expectations, anxious avoidance of problem confrontation, and negative
      experiences with the medical system. At follow-up, the majority are in good
      medical and psychological health. Few donors and recipients are suffering from
      disappointed expectations or unexpected treatment side effects. CONCLUSIONS: The
      Heidelberg consultation setting has proven useful for allowing open discussion
      about critical issues. In problem cases, prescribing a moratorium instead of
      rejecting donation helps to relax consultation anxiety. Psychological support
      after transplantation seems to be indicated for a minority with typical first
      year problems.

PMID- 14657686
TI  - One hundred percent patient and kidney allograft survival with simultaneous liver
      and kidney transplantation in infants with primary hyperoxaluria: a single-center
      experience.
AB  - BACKGROUND: Combined liver-kidney transplantation is the definitive treatment for
      end-stage renal disease caused by primary hyperoxaluria type I (PH1). The
      infantile form is characterized by renal failure early in life, advanced systemic
      oxalosis, and a formidable mortality rate. Although others have reported on
      overall results of transplantation for PH1 covering a wide age spectrum, none has
      specifically addressed the high-risk infantile form of the disease. METHODS: Six
      infants with PH1 underwent simultaneous liver-kidney transplantation at our
      center between May 1994 and August 1998. Diagnosis was made at 5.2+/-3.3 months
      of age, they were on dialysis for 11.8+/-2.3 months, and they underwent
      transplantation at 14.8+/-3.0 months of age when they weighed 10.6+/-1.7 kg.
      RESULTS: At a mean follow-up of 6.4+/-1.7 years (range, 3.9-8.1 years), we report
      100% patient and kidney allograft survival. There were no cases of acute tubular
      necrosis. Long-term kidney allograft function remained stable in all patients,
      with serum creatinine values of less than 1.1 mg/dL and a mean creatinine
      clearance of 99 mL/min/1.73 m2 at follow-up. Those who received combined
      hemodialysis and peritoneal dialysis pretransplant had lower posttransplant
      urinary oxalate values than those receiving peritoneal dialysis alone. There was
      improvement in growth and psychomotor and mental developmental scores after
      transplantation. CONCLUSIONS: Combined liver-kidney transplantation for the
      infantile presentation of PH1 is associated with excellent outcome when the
      approach includes early diagnosis and early combined transplantation, aggressive
      pretransplant dialysis, and avoidance of posttransplant renal dysfunction.

PMID- 14657688
TI  - Cytomegalovirus infection status predicts progression of heart-transplant
      vasculopathy.
AB  - BACKGROUND: Transplant vasculopathy (TVP) is the most common cause of death and
      retransplantation after heart transplantation. Human cytomegalovirus (HCMV)
      infection has been linked to atherosclerosis and to the development of TVP. A
      prospective study evaluating the relation between CMV infection and progression
      of TVP is lacking thus far. The purpose of the present study was to investigate
      the influence of CMV infection status on the progression of TVP within 1 year.
      METHODS: We enrolled 103 consecutive heart-transplant recipients who underwent
      routine cardiac catheterization and intracoronary ultrasound examination at study
      entry and after 1 year. Plaque progression determined by quantitative
      intracoronary ultrasound was used to define the severity of disease at baseline
      and at 1-year follow-up. At study entry, HCMV infection status was evaluated by
      immunological assays and reverse-transcriptase polymerase chain reaction (RT
      PCR). RESULTS: HCMV immunoglobulin (Ig)G/IgM seropositivity was found in 34 (33%)
      of transplant recipients, 11 of whom were HCMV PCR positive. The HCMV-positive
      group showed more advanced, calcified lesions (64.7% vs. 27.5%, P=0.002), and the
      maximal plaque thickness was significantly different from the HCMV IgG/IgM
      negative group (median [quartile] 1.36 [0.85, 1.88] vs. 1.05 [0.58, 1.34],
      P=0.02). In a logistic regression model, we demonstrate that HCMV IgG/IgM
      positivity is a predictor for the progression of TVP independent of
      cardiovascular risk factors, inflammatory markers, and platelet activation
      (P=0.038). In addition, HCMV PCR positivity even increases the risk for
      accelerated TVP (P=0.017) and, consecutively, transplant failure. CONCLUSIONS:
      HCMV infection status in transplant patients detects patients with increased risk
      for transplant failure caused by TVP.

PMID- 14657689
TI  - Oxidative stress in kidney transplant patients.
AB  - BACKGROUND: Little information is available about the role of oxidative stress in
      renal transplant patients. To evaluate the prevalence and severity of oxidative
      stress in renal transplantation, the authors conducted a cross-sectional study.
      METHODS: In 112 cadaver or living-donor kidney transplant recipients with a
      follow-up of at least 6 months and with plasma creatinine less than or equal to
      2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive
      oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC),
      serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured.
      RESULTS: The mean levels of Hcy (21.1 microM vs. <10 microM), ROS (302.7 U. Carr
      (Carratelli units) vs. 250-300 U. Carr), and TAOC (410.6 micromol/HclO/mL vs.
      >350 micromol/HclO/mL), were higher than the reference interval, whereas -SH
      groups, vitamin B12, s-F, and ery-F were within the normal range. In the
      multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and
      TAOC (P=0.0007) were independently associated with oxidative stress. At multiple
      regression analysis, -SH groups and ROS were directly and inversely related to
      hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between
      -SH groups and blood pressure levels (P=0.0095). CONCLUSIONS: Renal transplant
      patients have a pattern of increased oxidant stress that is counterbalanced by an
      enhancement of the antioxidant mechanisms. Besides the well-known risk factors,
      the authors found that anemia is an independent risk factor for an increase of
      ROS. Further studies are needed to evaluate whether the correction of anemia
      might prevent or reduce the oxidative stress in renal transplant patients.

PMID- 14657690
TI  - Survival gain after liver transplantation for patients with alcoholic liver
      disease: a comparison across models and centers.
AB  - BACKGROUND: Prognostic models, which estimate survival probabilities, enable the
      survival benefit from a procedure to be assessed and allow the comparison of
      outcomes between centers. We therefore compared three models that estimate
      survival in the absence of transplantation for patients with alcoholic liver
      disease (ALD) to assess survival benefit after transplantation and to compare the
      outcomes in the six liver-transplant centers in England. METHODS: The Beclere and
      Birmingham models and the Model for End-Stage Liver Disease (MELD) were used to
      estimate survival in the absence of transplantation in a cohort of 82 patients
      with end-stage ALD. Posttransplant survival in the same cohort of patients was
      calculated using conventional survival techniques. Each individual's short-term
      survival gain after liver transplantation was also calculated and compared across
      UK liver transplant centers. RESULTS: The expected gain in survival differed
      substantially depending on the model used. Over the 4-year study period, the
      survival gain for all ALD patients was 1.70 years (95% confidence interval [CI]
      1.37-2.03) using the Beclere model, 0.95 years (CI 0.60-1.30) using MELD, and
      0.08 years (CI -0.31-0.47) using the Birmingham model. Two centers consistently
      had greater estimated survival gains up to 4 years postliver transplant
      regardless of the model used to estimate nontransplant survival. CONCLUSIONS:
      These findings suggest that although liver transplantation is associated with an
      improvement in survival, the gain over 4 years is modest. The three models are
      poorly correlated and should be applied with caution. Survival gain does,
      however, appear to vary between centers.

PMID- 14657691
TI  - Progression of liver fibrosis in patients with chronic hepatitis C after
      orthotopic liver transplantation.
AB  - BACKGROUND: Hepatitis C virus (HCV)-related cirrhosis is the leading indication
      for orthotopic liver transplantation (OLTx). HCV recurrence is universal after
      OLTx, with a highly variable course. This study aimed to find factors that affect
      progression of fibrosis in recurrent HCV. METHODS: Fifty-eight HCV patients
      underwent OLTx at our center who were selected on the basis of available preOLTx
      serum or explanted liver sample and liver biopsy obtained at least 6 months
      postOLTx. All liver biopsies were performed when clinically indicated and were
      scored using the modified Hepatitis Activity Index (HAI). Primary
      immunosuppression consisted of tacrolimus and prednisone. RESULTS: The group
      included 41 males (mean age 49.6 years). HCV genotype distribution was 1a, 31
      (53%); 1b, 16 (28%), and others 11 (19%). The mean follow-up was 53.1 months.
      Patients with genotype 1a (n=31; mean 46.3 months) had significantly lower
      fibrosis-free survival analyzed by the presence of fibrosis stages 5 and 6 when
      compared with other genotypes (n=27; mean 60.1 months; P=0.0088, log rank test).
      Mean HAI scores were significantly higher in HCV genotype 1a, although there were
      no differences in survival between genotypes. Similarly, patients with
      cytomegalovirus (CMV) infection postOLTx (n=4) had a higher fibrosis progression
      rate compared with those without CMV (n=54) (mean fibrosis-free survival 29.0 vs.
      53.0 months P=0.0004, log-rank test). Human leukocyte antigen matching and rate
      of acute rejection did not influence progression of fibrosis. CONCLUSION:
      Patients with HCV genotype 1a and those developing CMV postOLTx have a higher
      rate of hepatic fibrosis progression after OLTx for HCV-related chronic liver
      disease.

PMID- 14657692
TI  - The heart-allocation simulation model: a tool for comparison of transplantation
      allocation policies.
AB  - BACKGROUND: Numerous studies have investigated prognostic factors for the
      survival of transplant candidates waiting for a donor organ, but little is known
      about the impact of allocation policies on waiting list outcome. Simulation
      models would allow a comparison of different policies for allocating donor hearts
      on pretransplant outcome. METHODS: A model was built for the Eurotransplant
      waiting list for heart transplantation. Survival and delisting distributions were
      estimated from the Eurotransplant transplant candidate inflow between 1995 and
      2000 (n=7,142). Other characteristics were obtained directly from the transplant
      candidate inflow of 1999 and 2000 (n=2,097) and the donor organs of 1998 and 1999
      (n=1,520). Overall and subgroup waiting list mortality were estimated for
      allocation policies differing by ABO blood group, border, and clinical profile
      rules. RESULTS: The model estimated that international organ exchange reduces
      waiting list mortality in the different countries by 1.9% to 12.4%. An allocation
      policy incorporating the initial clinical profile of the transplant candidates
      further reduced waiting list mortality by 1.7%. Changing ABO rules toward
      identical matching yielded a slightly more equitable survival for the different
      groups, without an overall effect on mortality. The best possible allocation
      policy is the policy where organs are allocated to patients that are at highest
      risk of dying, and withholding organs from patients that would eventually delist
      because of improvement. CONCLUSIONS: Patients benefit from international organ
      exchange and by a heart allocation scheme based on clinical profiles. Timely
      delisting of patients who are-temporarily-too well for transplantation is the
      best waiting list policy.

PMID- 14657693
TI  - Prevalence and treatment of decreased bone density in renal transplant
      recipients: a randomized prospective trial of calcitriol versus alendronate.
AB  - BACKGROUND: Reduced bone mineral density (BMD) is common in long-term renal
      transplant recipients and results in a high incidence of fractures. The optimal
      therapy for these patients is not known. METHODS: Baseline BMD determinations
      were obtained in 211 long-term adult renal transplant recipients. One hundred and
      seventeen patients with a reduced BMD (T score < or = -1) were randomly assigned
      to treatment with alendronate and calcium (n=60) versus calcitriol and calcium
      (n=57). Of these, 46 and 51 patients, respectively, completed 1 year of
      treatment. Forty-nine patients who were not eligible or did not consent to the
      trial were followed prospectively. RESULTS: Reduced baseline BMD (T score < or = 
      1) was present in 159 (78.7%) of patients at the lumbar spine or femur. There was
      no significant loss of BMD in the prospectively followed patients during 2.7
      years. The average lumbar BMD increased from 0.984+/-0.149 to 1.025+/-0.143 g/cm2
      (P<0.001) with alendronate and from 1.014+/-0.15 to 1.034+/-0.146 g/cm2 (P=0.002)
      with calcitriol. BMD at the femur increased from 0.809+/-0.092 to 0.836+/-0.107
      g/cm2 (P<0.001) with alendronate and from 0.830+/-0.144 to 0.857+/-0.125 g/cm2
      (P=0.023) with calcitriol. CONCLUSIONS: One year of treatment with alendronate or
      calcitriol, both with calcium supplementation, resulted in significant increases
      in BMD at the lumbar spine and femur, with a trend toward alendronate being more
      effective at the spine (P=0.082). Further studies are needed to determine whether
      BMDs continue to increase after 1 year and whether there is any additional
      benefit to combining vitamin D and alendronate. Larger studies are needed to
      determine whether treatment decreases fracture rates.

PMID- 14657694
TI  - Presentation of donor major histocompatibility complex antigens by bone marrow
      dendritic cell-derived exosomes modulates allograft rejection.
AB  - BACKGROUND: Dendritic cells secrete a population of "antigen-presenting
      vesicles," called exosomes, expressing functional class I and II major
      histocompatibility complex (MHC) and co-stimulatory molecules. The subcutaneous
      administration of syngeneic exosomes expressing tumor antigens has been shown to
      induce specific antitumor immune responses in vivo. The authors hypothesized that
      antigen presentation by exosomes, depending on the context of their
      administration, may induce tolerance rather than immunity. METHODS: The authors
      therefore tested the capacity of exosomes derived from donor bone marrow
      dendritic cells, given before transplantation, to modulate heart allograft
      rejection. RESULTS: The authors show here that donor type but not syngeneic
      exosomes induced a significant prolongation of allograft survival, with a few
      recipients having long-term graft survival. During the first week after
      transplantation, allografts from exosome-treated rats displayed a significant
      decrease in graft-infiltrating leukocytes and in the expression of interferon
      gamma mRNA compared with allografts from untreated animals. Moreover, when tested
      in vitro, spleen CD4+ T cells from exosome-treated recipients displayed a
      significant decrease in anti-donor responses, suggesting a decrease in anti-donor
      T-cell responses. However, the authors also found that allogeneic donor-derived
      exosomes increased anti-donor MHC class II alloantibody production. CONCLUSIONS:
      The authors demonstrate an effect of allogeneic exosomes on the modulation of
      immune responses in vivo, suggesting that, like donor cells, exosomes can
      stimulate or regulate antigen-specific immune responses.

PMID- 14657695
TI  - Significant prolongation of orthotopic corneal-graft survival in FTY720-treated
      mice.
AB  - BACKGROUND: The novel immunomodulator, FTY720, mainly acts through sequestering
      of lymphocytes to secondary lymphatic tissue, thereby suppressing their
      infiltration into grafted organs. This study aimed to investigate its influence
      on corneal-graft survival. METHODS: Sixteen BALB/c mice (H-2d) received corneal
      transplants from C3H (H-2k) mice. Eight mice were treated with FTY720 (10 mg/kg
      per day) orally from day -1 to day 11, and all animals received 0.1%
      dexamethasone eye drops for the same time. In addition, eyes and regional lymph
      nodes from similarly treated animals were subjected to immunohistochemistry and
      proliferation assays. RESULTS: FTY720 significantly prolonged graft survival from
      28+/-8.1 to 36.5+/-7.1 days (P=0.021). In treated animals, corneal infiltration
      by CD4+ and F4/80+ cells was reduced from 70.8+/-60.3 to 7.0+/-9.0 (P=0.004) and
      from 97.5+/-30.7 to 44.8+/-24.9 (P=0.01) cells, respectively, and allogeneic T
      cell proliferation was decreased. CONCLUSIONS: FTY720 treatment substantially
      protects corneal allografts and may provide an immunomodulatory strategy in
      clinical corneal transplantation.

PMID- 14657696
TI  - Intravesical bacillus Calmette-Guerin for the treatment of superficial bladder
      cancer in renal transplant patients.
AB  - BACKGROUND: Intravesical instillations with bacillus Calmette-Guerin (BCG) is
      considered the treatment of choice in the prophylaxis of high-grade superficial
      bladder carcinoma and in the treatment of carcinoma in situ (CIS) of the bladder.
      METHODS: There is no previous experience with BCG treatment in patients with
      renal transplantation. Theoretically, immunosuppression is a contraindication
      because of the risk of severe morbidity and sepsis. We present our experience
      with endovesical BCG in three renal transplant patients, under immunosuppressive
      treatment, with high-grade superficial bladder cancer and CIS. RESULTS: Two
      patients are free of disease at 17 and 60 months. One patient developed disease
      recurrence and underwent a radical cystectomy. There was neither change in renal
      function nor any clinical evidence of tuberculous infection. CONCLUSIONS:
      Intravesical BCG in superficial bladder cancer and/or CIS is a valid option, with
      no added morbidity to renal transplant patients.

PMID- 14657697
TI  - Studies on effects of calcineurin inhibitor withdrawal on arterial distensibility
      and endothelial function in renal transplant recipients.
AB  - Whether withdrawal of calcineurin inhibitors has a beneficial effect on disturbed
      endothelial function and large artery distensibility in renal transplant
      recipients is not clear. We studied the effects of cyclosporine A (CsA)
      withdrawal on arterial compliance and endothelium-dependent flow-mediated
      vasodilatation (FMD) in a prospective, randomized trial; 24 renal transplant
      recipients receiving mycophenolate mofetil were randomized to withdrawal (n=12)
      or continuation of CsA (n=12). At baseline and after 6 months, carotid and
      brachial artery distensibility coefficients and brachial FMD were measured.
      Brachial distensibility coefficients increased in both groups (withdrawal: 11.1+/
      1-14.9+/-2 10(-3)/kPa, continuation: 10.7+/-1-15.2+/-3 10(-3)/kPa, P<0.05,
      respectively). However, there was no significant effect of treatment on carotid
      artery distensibility coefficients, FMD, or graft function. Withdrawal of CsA
      failed to improve carotid artery distensibility or brachial FMD in patients after
      renal transplantation. Our data indicate that CsA treatment does not contribute
      significantly to endothelial dysfunction observed in renal transplant recipients.

PMID- 14657698
TI  - Specific and durable elimination of antibody to donor HLA antigens in renal
      transplant patients.
AB  - BACKGROUND: Donor-specific antibody (DSA) is the major barrier to success of
      kidney transplants. Attempts to deal with this problem have used plasmapheresis
      to remove antibodies or high-dose pooled immunoglobulin (IVIg) to down-regulate
      DSA. However, elimination of antibodies by these methods has been limited in
      duration or scope. METHODS: We have confirmed the presence of immunoglobulin
      (Ig)G antibody to one or more donor HLA antigens in 49 patients treated with
      alternate-day, single-volume plasmapheresis followed by low-dose cytomegalovirus
      (CMV) hyperimmune globulin (CMV-Ig) combined with quadruple immunosuppression. We
      examined the effect of the treatment protocol on antibodies to donor HLA, third
      party HLA, and nominal antigens. RESULTS: At the end of treatment, 63% of
      patients had lost antibody to donor HLA, whereas only 27% had lost antibody to
      third-party HLA (P<0.001). More strikingly, loss of antibody to donor and third
      party HLA antigens occurred in 89% and 19%, respectively, of patients followed
      for 2 or more months after end of treatment (P<0.0001). No elimination of
      antiviral antibodies tested was seen. With one exception, elimination of DSA
      appeared to be independent of antibody titer or specificity, the number of
      different antibody specificities, or whether or not the target antigen was a
      repeat mismatch. The effect appears to be long lasting, with no return of DSA
      observed in patients followed for an average of 13 months. CONCLUSIONS:
      Plasmapheresis and low-dose CMV-Ig combined with traditional immunosuppression is
      effective in producing a specific and durable elimination of antibody to donor
      HLA.

PMID- 14657699
TI  - Equivalent functional nuclear factor of activated T cell 1 mRNA and protein
      expression in cord blood and adult T cells.
AB  - Cord blood (CB) cells are now an important source of stem cells for bone marrow
      reconstitution as a result of the decreased risk of graft-versus-host disease
      that was attributed to previously reported absent or diminished nuclear factor of
      activated T (NFAT) cell 1 expression by CB T cells. This study reexamines NFAT1
      expression in CB T cells. CB T cells were examined for NFAT1 mRNA and protein
      expression. These cells were then stimulated, and NFAT1 translocation and
      interleukin-2 production were assessed. Our results show that resting CB CD4+ T
      cells express NFAT1 mRNA and protein at levels similar to their adult
      counterparts. On stimulation, NFAT1 is translocated into the nucleus where DNA
      binding can occur, whereas calcineurin inhibition prevents interleukin-2
      production. We conclude that differential responsiveness of CB T cells cannot be
      attributed to differences at the level of NFAT1 expression or its ability to
      function in these cells but may represent an altered sensitivity to stimulation.

PMID- 14657700
TI  - Response to letter from Yoshino et al.: Vascular closure staples for experimental
      organ transplantation.

PMID- 14657701
TI  - Hand-assisted laparoscopic right-donor nephrectomy in a patient with situs
      inversus.

PMID- 14657702
TI  - Donor lymphocyte infusion for late relapse followed by kidney transplantation for
      end-stage renal failure after allogeneic bone marrow transplantation for chronic
      myeloid leukemia.

PMID- 14657703
TI  - Mixed chimerism of thyroid follicle cells after allogeneic bone marrow
      transplantation.

PMID- 14657704
TI  - Fatal Bacillus cereus meningitis without inflammatory reaction in cerebral spinal
      fluid after bone marrow transplantation.

PMID- 14657705
TI  - Sparing interleukin-10 receptor expression by glucocorticoids is a prerequisite
      for the synergistic immunosuppressive effects of interleukin-10 and
      glucocorticoids.

PMID- 14657707
TI  - Solitary pancreas transplantation in Wolfram syndrome.

PMID- 14657708
TI  - p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in
      patients with chronic pancreatitis.
AB  - Patients with long-standing chronic pancreatitis are thought to be at increased
      risk of developing pancreatic ductal adenocarcinoma, but the mechanism for this
      increased risk is unknown. Since increasing evidence supports the notion that
      infiltrating pancreatic ductal adenocarcinomas arise from pancreatic
      intraepithelial lesions (PanINs), we sought to determine if patients with chronic
      pancreatitis harbor PanINs with alterations in tumor suppressor genes that are
      associated with infiltrating pancreatic ductal adenocarcinoma. We identified 122
      patients with a diagnosis of chronic pancreatitis and 29 patients with a well
      differentiated pancreatic endocrine tumor that underwent pancreatic surgery at
      the Johns Hopkins Hospital from 1985 to 1999. PanINs from each resection specimen
      were identified, graded, counted, and correlated with smoking and alcohol
      history. The expression patterns of p16 and Smad4 were determined in a subset of
      PanINs by immunohistochemistry, and the pattern of labeling compared with that
      seen in PanINs associated with infiltrating adenocarcinoma of the pancreas as
      identified in prior studies, and to PanINs associated with pancreatic endocrine
      tumor. Duct lesions were present in 80 of the 122 pancreata with chronic
      pancreatitis (66%). Of 405 duct lesions identified in the chronic pancreatitis
      group, 7.6% were reactive changes, 65.5% were PanIN-1A, 18% were PanIN-1B, 7.4%
      were PanIN-2, and 1.5% were PanIN-3. Within the pancreatic endocrine tumor group,
      22 PanINs were identified: 15 PanIN-1A, 4 PanIN-1B, and 3 PanIN-2. There were
      significantly fewer high-grade PanINs in the pancreata with chronic pancreatitis
      than in pancreata with pancreatic adenocarcinoma (P < 0.0001). Within the chronic
      pancreatitis group, the 80 patients with PanINs were significantly older than the
      42 patients without PanINs (mean age 57.0 +/- 14.1 years vs. 50.9 +/- 14.7 years,
      P = 0.01). Smoking history was not associated with PanIN prevalence or grade, but
      patients who reported a history of excessive alcohol consumption had fewer PanINs
      (25 of 44 harbored PanINs, 57%) than those who did not (54 of 74, 73%, P = 0.07).
      In the chronic pancreatitis group, 0% of PanIN-1A, 11% of the PanIN-1B, 16% of
      the PanIN-2, and 40% of the PanIN-3 lesions showed loss of p16 expression,
      whereas all of the PanINs from patients with an pancreatic endocrine tumor
      retained p16 expression. All of the PanINs analyzed from patients with chronic
      pancreatitis retained normal Smad4 expression. We conclude that a significant
      minority of PanINs arising in patients with chronic pancreatitis show loss of p16
      expression. This alteration, common to pancreatic cancer-associated PanINs, may
      contribute to the predisposition of patients with chronic pancreatitis to develop
      pancreatic ductal adenocarcinoma.

PMID- 14657709
TI  - Declining estrogen receptor-beta expression defines malignant progression of
      human breast neoplasia.
AB  - It has been shown that the risk of breast cancer developing in certain
      morphologically identifiable benign breast lesions correlates with expression of
      estrogen receptor alpha (ER-alpha). Although ER-alpha and ER-beta genes share a
      large degree of homology, it is generally thought that their distribution and
      functions are substantially different in many tissues. Recent development of
      reliable antibodies to ER-beta has provided this first opportunity to test the
      hypothesis that the likelihood of malignant transformation in morphologically
      benign breast lesions can be accurately defined by the distribution and level of
      ER-beta expression relative to that of ER-alpha. Using a monoclonal antibody, ER
      beta protein expression has been analyzed in 53 normal breasts and compared with
      a cohort of histologically distinct breast lesions of different prognostic risk
      (54 hyperplasia of usual type, 35 ductal carcinoma in situ, and 141 invasive
      cancers). All of these tissues were also assessed for ER-alpha. Expression of ER
      beta protein was also analyzed in an additional spectrum of benign breast lesions
      with low or negligible risk of progression to malignancy. The median proportion
      of cells expressing ER-beta was highest in normal breast lobules (median 94.33%,
      interquartile range 78.25-99.00) but declined significantly through usual ductal
      hyperplasia (median 76.67, interquartile range 49.17-95.00, P = 0.002) and ductal
      carcinoma in situ (median 70.00, interquartile range 59.00-85.00, P = 0.009) to
      invasive cancer (median 60.00, interquartile range 50.00-80.00, P < 0.001). An
      appreciable proportion (33.81%) of ER-alpha-negative invasive cancers expressed
      ER-beta. A high but variable level of ER-beta expression occurred in the benign
      lesions. The data from the intact histologic tissues were evaluated with respect
      to the relative expression of ER-alpha and ER-beta in five mammary cell lines of
      different behavioral phenotype (MCF7, ZR-75, T47D, MDAMB231, HUMA121). The highly
      significant differences in expression and distinct tissue distributions of ER
      alpha and ER-beta within the histologic lesions of defined risk, together with
      the data from the cell lines, support the original hypothesis that the tissue
      concentration, relative occurrence, and/or interaction of these two types of
      estrogen receptor may play an important role in modulating mammary tumorigenesis.

PMID- 14657710
TI  - Peripheral T-cell lymphomas expressing CD30 and CD15.
AB  - Coexpression of CD30 and CD15 is typically associated with classic Hodgkin's
      lymphoma (HL). Peripheral T-cell lymphomas (PTCLs) can often display histologic
      features that simulate classic HL. However, reports of PTCLs coexpressing both
      CD30 and CD15 have been infrequently described. We report 11 cases of PTCL in
      which at least a subset of the neoplastic cells coexpressed CD30 and CD15. The
      patients included 4 women and 7 men and age ranged from 43 to 83 years (median,
      62 years). Nine of 10 patients had advanced stage III or IV disease at
      presentation. Nodal involvement predominated in 8 of 11 patients, whereas 2
      patients presented primarily with skin involvement. Two distinct groups were
      identified based on morphologic and immunophenotypic features. The first group of
      5 cases had histologic features mimicking classic HL with CD30+, CD15+ Reed
      Sternberg (RS)-like cells in an inflammatory background of varied extent and
      composition. The background lymphoid cells showed minimal cytologic atypia. The
      RS-like cells were negative for CD20 and CD79a in all cases, and CD45 expression
      was absent in 4 of 5 cases. The RS-like cells expressed CD25 and at least one T
      cell-associated marker in all cases. The background T-cell population showed
      convincing subset predominance in 4 of 5 cases and loss of T-cell-associated
      antigens in 3 of 5 cases and coexpression of CD30 and CD15 in one case. The
      second group of 6 cases had morphologic features more in keeping with PTCL than
      classic HL. The proportion of neoplastic cells coexpressing CD30 and CD15 varied.
      Loss of T-cell antigens was noted in all cases and CD4 predominated in 4 of 5
      cases. Three of the 6 cases expressed CD45. PCR analysis revealed clonal T-cell
      receptor gamma (TCR-gamma) chain gene rearrangements in 9 of 11 cases, but no
      immunoglobulin heavy (IgH) chain gene rearrangements. In situ hybridization
      studies for Epstein-Barr virus were negative in all cases. In some PTCL cases,
      the overlap with classic HL can be striking, and combined immunophenotypic and
      molecular studies are often necessary to confirm the diagnosis.

PMID- 14657711
TI  - Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings
      in 19 cases.
AB  - Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered
      to have indolent biologic potential. However, outcome data are scant, with only
      one documented metastasis and death. We describe clinicopathologic features of
      ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43
      to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed
      by transurethral resection in 15 cases, by needle biopsy in 3 cases, and
      unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma.
      Histologically, cribriform or adenoid cystic patterns predominated in 12 cases
      and basal cell carcinoma pattern in 7. Five cases had prominent perineural
      invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but
      not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy,
      2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed
      extraprostatic extension in 5 cases and involved the bladder margin in 3.
      Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and
      corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients
      died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer,
      and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially
      aggressive neoplasm requiring ablative therapy.

PMID- 14657712
TI  - Dedifferentiated adamantinoma with revertant mesenchymal phenotype.
AB  - In adamantinoma of long bones, an osteofibrous dysplasia-like form with scattered
      epithelial elements and a classic form with abundant epithelium are
      distinguished. Osteofibrous dysplasia-like adamantinomas occur in children and
      adolescents and behave relatively benign, whereas classic adamantinomas
      predominate in adults and have a more aggressive clinical course. Because some
      osteofibrous dysplasia-like tumors have progressed to classic adamantinomas, it
      is hypothesized that the former is a potential precursor of the latter, showing
      mesenchymal-to-epithelial transformation. We report a new morphologic variant of
      adamantinoma in three patients with sarcomatoid transformation of the epithelial
      component: one in a primary tumor and two in local recurrences. One patient died
      of metastatic disease. Histologically, the tumors showed loss of the original
      characteristic epithelial differentiation with transition to fields of highly
      pleomorphic cells without epithelial features, high mitotic count, and deposition
      of osteoid and chondroid matrix. These dedifferentiated areas showed pankeratin
      positivity as well, although there were some changes in keratin subclass profile
      compared with other classic adamantinomas. This peculiar variant of long bone
      adamantinoma shows that in addition to mesenchymal-to-epithelial transformation
      in the early stage of development, progression to an aggressive subtype may be
      associated with epithelial-to-mesenchymal transition ("sarcomatoid
      dedifferentiation"), in which the epithelial immunophenotype is conserved.
      Thereby it may serve as an example of the plasticity of the mesenchymal
      phenotype. When confronted with a biopsy of a cortical tumor of the tibia showing
      sarcomatoid morphology and keratin positivity, adamantinoma should be included in
      the differential diagnosis, as its distinction has important implications for
      treatment and prognosis.

PMID- 14657713
TI  - Primary cutaneous diffuse large B-cell lymphoma: prognostic significance of
      clinicopathological subtypes.
AB  - Classification and subdivision of primary cutaneous diffuse large B-cell lymphoma
      (PCDLBCL) are a matter of ongoing debate. In this study we assessed the
      morphologic, immunophenotypic, and clinical features of 30 cases of PCDLBCL
      identified during a review of all primary cutaneous B-cell lymphomas in the
      Scotland and Newcastle Lymphoma Group database. We also determined the number of
      cases harboring t(14;18) using a polymerase chain reaction and primers to the
      major breakpoint cluster region. The effect on prognosis of a variety of clinical
      and pathologic factors was assessed for the group of 30 PCDLBCL and the 5-year
      disease-specific survival (DSS) of this cohort compared with that of 195 cases of
      stage I diffuse large B-cell lymphoma arising primarily in lymph nodes, also
      identified from within the Scotland and Newcastle Lymphoma Group database.
      Location on the leg was the only independent prognostic factor for determining
      outcome in PCDLBCL (67% 5-year DSS compared with 100% for the upper body; P =
      0.0047). The presence of multiple lesions, involvement of more than one body
      site, and expression or not of CD10, bcl-2, bcl-6, and CD10 and bcl-6, had no
      effect on survival. Compared with cases arising above the waist, those on the leg
      were more often female, were of an older age, and had a significantly higher
      incidence of bcl-2 expression (P = 0.002) as well as the aforementioned poorer
      prognosis. They also showed more frequent co-expression of CD10 and bcl-6,
      supporting a follicle center cell origin for some, but this difference was not
      statistically significant. Although there was no significant difference in the 5
      year DSS between the group of PCDLBCL and the cases of stage I nodal diffuse
      large B-cell lymphoma (88% 5-year DSS vs. 78%; P = 0.06), the latter were
      generally treated with more aggressive therapy. Moreover, a significant
      difference in 5-year DSS was seen when the nodal DLBCLs were compared with
      PCDLBCLs arising above the waist (78% vs. 100% respectively; P = 0.0135). These
      results support the current EORTC approach of subdividing PCLBCL on the basis of
      site to produce prognostically relevant groupings.

PMID- 14657714
TI  - Human herpesvirus-8 latent nuclear antigen-1 expression in endemic Kaposi
      sarcoma: an immunohistochemical study of 16 cases.
AB  - Human herpesvirus-8 (HHV-8) infection is considered the initiating factor in all
      forms of Kaposi sarcoma (KS). Latent nuclear antigen (LNA-1) is constitutively
      expressed in all HHV-8-infected cells. An antibody to LNA-1 has recently become
      commercially available. The current study addresses the role of
      immunohistochemistry in the diagnosis of KS, particularly the endemic form. Seven
      recent cases of KS, 1 atypical vascular lesion in a patient subsequently
      diagnosed with KS, and 16 endemic cases collected in South Africa in the early
      1960s were stained with an antibody to LNA-1. Nine benign vascular lesions and
      three angiosarcomas were also stained. All 7 recent cases expressed the antigen
      as did the atypical vascular lesion. Of particular interest was the finding that
      10 of the 16 endemic cases were positive. None of the other vascular lesions
      showed staining. A subset of the endemic lesions was stained for CD31, an antigen
      universally expressed in KS. CD31 staining was reduced compared with a positive
      control suggesting that the current study may underestimate the sensitivity of
      LNA-1 immunohistochemistry in endemic KS because of poor antigen preservation in
      the archival tissue. Our results confirm the utility of LNA-1
      immunohistochemistry as an aid in the diagnosis of KS.

PMID- 14657715
TI  - Analysis of protein expression and gene mutation of c-kit in colorectal
      neuroendocrine carcinomas.
AB  - Primary neuroendocrine carcinomas of the colon are rare but highly aggressive
      malignancies. The recent observations that c-kit protooncogene, a tyrosine
      kinase, is overexpressed in a subset of small cell lung cancer and that selective
      kinase inhibitors block the in vitro growth of small cell lung cancer cell lines
      prompted us to investigate the expression and mutation status of the c-kit gene
      in colorectal neuroendocrine carcinomas. Sixty-six cases of primary colorectal
      neuroendocrine carcinoma were collected from 13 institutions, including 36 small
      cell carcinomas and 30 moderately differentiated neuroendocrine carcinomas.
      Immunohistochemical studies using a polyclonal antibody against c-kit protein
      (CD117) demonstrated a strong and diffuse cytoplasmic staining in 15 cases (23%),
      which were relatively equally distributed in the small cell and moderately
      differentiated subgroups. As controls, 25 conventional colorectal
      adenocarcinomas, 26 colorectal adenomas and 19 colorectal carcinoid tumors were
      all negative, whereas 15 gastrointestinal stromal tumors were all positive, for
      kit expression. In contrast to gastrointestinal stromal tumors, kit
      overexpressing neuroendocrine carcinomas showed no mutations in the juxtamembrane
      domain (exon 11) of the c-kit gene as determined by mutational analysis. Kaplan
      Meier analysis with the log-rank test revealed that the patients with kit
      positive tumors did not differ significantly in survival from those with kit
      negative tumors (P = 0.77). These results indicate that c-kit overexpression
      observed in a subset of colorectal neuroendocrine carcinomas may not be mediated
      via activating mutations, and does not appear to be an initiating event during
      tumorigenesis because of lack of c-kit expression in other types of colorectal
      epithelial neoplasms. More importantly, our observations may have potential
      therapeutic implications since specific tyrosine kinase inhibitors have shown
      promise in the management of patients with kit-expressing malignancies.

PMID- 14657716
TI  - Molecular evidence of anaplastic transformation in coexisting well-differentiated
      and anaplastic carcinomas of the thyroid.
AB  - Anaplastic thyroid cancer is a rare but nearly universally fatal tumor.
      Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from
      transformation of preexisting or coexisting well-differentiated thyroid
      carcinomas. At the molecular level, the mutations responsible for the anaplastic
      transformation are incompletely understood, although the mutational events are
      thought to involve tumor suppressor genes. To examine transformation from a well
      differentiated thyroid carcinoma to anaplastic carcinoma, we studied coexisting
      well-differentiated (Hurthle cell and papillary carcinoma) and anaplastic tumors
      with a molecular genotyping panel of tumor suppressor genes associated with
      thyroid neoplasia. The patterns of allelic loss in our results showed that the
      majority of cases have a core of conserved mutations in the two morphologically
      distinct areas and substantial increases in mutation rates in the anaplastic
      components.

PMID- 14657717
TI  - Current diagnostic methods of HER-2/neu detection in breast cancer with special
      regard to real-time PCR.
AB  - In this study we compare different diagnostic methods to measure HER-2/neu gene
      amplification in breast cancer with special regard to real-time polymerase chain
      reaction. Fifty specimens of breast cancer were analyzed, and the use of laser
      assisted microdissection prior to PCR was investigated. A total of 38 of 50 cases
      showed HER-2/neu overexpression in immunohistochemistry. In the 2+ scored group,
      2 of 23 cases turned out to be amplified after FISH analysis and 14 of 15 cases
      in the 3+ group were amplified. Of the 16 amplified cases, 3 initially were
      measured as nonamplified by real-time PCR but showed amplification after laser
      capture microdissection. One case showed amplification by PCR but turned out to
      have only one copy of chromosome 17 by FISH. All 0 or 1+ scored cases were
      measured as nonamplified both by FISH and PCR. Initial concordance rate between
      FISH and PCR was 92% and could be increased to 98% using laser-assisted
      microdissection. FISH and PCR showed high diagnostic accuracy and concordance
      while immunohistochemistry overestimates amplification within the 2+ scored
      group. Therefore, either FISH or PCR should be applied in cases scored 2+ by
      immunohistochemistry. Diagnostic accuracy of PCR can be increased using laser
      assisted microdissection.

PMID- 14657718
TI  - Interobserver reproducibility of histopathologic prognostic variables in primary
      cutaneous melanomas.
AB  - BACKGROUND: The prognosis for patients with localized primary cutaneous melanoma
      is known to depend principally on tumor thickness, and to a lesser extent on
      ulcerative state and Clark level. We have recently found in an analysis of 3661
      patients that tumor mitotic rate (TMR) is also an important prognostic parameter,
      ranking second only to tumor thickness. However, few studies have assessed the
      accuracy and reproducibility with which these features of a melanoma are recorded
      by histopathologists. AIM: To assess interobserver reproducibility of major
      pathologic prognostic parameters in cutaneous melanoma. METHODS: Single
      hematoxylin and eosin-stained slides of 69 dermally invasive primary cutaneous
      melanomas were circulated among six pathologists with differing experience in the
      assessment of melanocytic tumors. The observers independently determined the
      tumor thickness, Clark level of invasion, ulcerative state, and TMR for each
      lesion. Intraclass correlation coefficients and kappa scores for multiple ratings
      per subject were calculated. RESULTS: The intraclass correlation coefficients
      were 0.96 for tumor thickness and 0.76 for TMR. The kappa scores were 0.83 for
      ulcerative state and 0.60 for Clark level. These results indicated excellent
      agreement among the pathologists for measurements of tumor thickness, ulcerative
      state, and TMR and fair to good agreement for Clark level. CONCLUSIONS:
      Appropriately trained and experienced histopathologists can assess prognostically
      important features of melanomas accurately and reproducibly. Given our recent
      finding of the significance of TMR in determining prognosis, it is important that
      this feature be assessed by a standardized method and documented for all primary
      cutaneous melanomas.

PMID- 14657721
TI  - Nailing a rare diagnosis.

PMID- 14657719
TI  - Composite Hodgkin lymphoma and mantle cell lymphoma: two clonally unrelated
      tumors.
AB  - Association of Hodgkin lymphoma and non-Hodgkin lymphoma is rare and,
      specifically, the combination of Hodgkin lymphoma and mantle cell lymphoma has
      not been previously described. Here we describe composite mantle cell lymphoma
      and Hodgkin lymphoma affecting the spleen in one case and the eyelid and cervical
      lymph nodes in a second. In both, nodules of classical Hodgkin lymphoma were
      intermixed with diffuse or nodular areas of typical mantle cell lymphoma.
      Immunohistochemical and molecular analyses confirmed cyclin D1 overexpression
      secondary to the translocation t(11;14) in the small mantle cell lymphoma
      component; with CD30, CD15, and EBV expression in the Hodgkin and Reed-Sternberg
      cells. Finally, clonal analysis of rearranged immunoglobulin genes performed on
      microdissected Hodgkin and Reed-Sternberg and mantle cell lymphoma cells provided
      definite evidence of separate clonal origins of the two tumors in the patients.
      These EBV-positive, clonally unrelated tumors seem to represent true composite
      neoplasms, in contrast to cases showing merely clonal progression.

PMID- 14657725
TI  - Anxiety disorders: helping your patient conquer her fears.

PMID- 14657726
TI  - Managing pelvic fractures.

PMID- 14657727
TI  - New strategies for treating patients with heart failure.

PMID- 14657728
TI  - The art of nursing.

PMID- 14657729
TI  - Patient education series. How to use your medicine safely.

PMID- 14657730
TI  - Put a realistic spin on geriatric assessment.

PMID- 14657731
TI  - Close to the vest: a novel way to keep airways clear.

PMID- 14657732
TI  - Vaccination do's and don'ts.

PMID- 14657733
TI  - Reexpansion pulmonary edema.

PMID- 14657735
TI  - NPs speak out about the less fortunate.

PMID- 14657736
TI  - A clinician's view of abortion.

PMID- 14657737
TI  - Health and weight perceptions of obese students.

PMID- 14657738
TI  - A new approach to childhood vaccination.

PMID- 14657739
TI  - Implications of unrecognized severe acute respiratory syndrome.

PMID- 14657740
TI  - Herpes simplex virus type 2: an update.

PMID- 14657741
TI  - DXA valuable for bone mineral density testing.

PMID- 14657742
TI  - Tetanus diagnosis sometimes elusive.

PMID- 14657743
TI  - Prevention key to managing swimmer's itch.

PMID- 14657744
TI  - Preventive measures for axial symptoms following cervical laminoplasty.
AB  - We have modified the operative procedure of laminoplasty and changed the
      postoperative therapy since 1997. In the modified group, several modifications
      were incorporated. The open door type of cervical en bloc laminoplasty was
      performed. 1) Bone grafts in the open gap were placed at three levels only. 2)
      Bone grafting in the hinged side was not performed. 3) The neck collar was worn
      for only 1 month. 4) The doctors explained the importance of the neck muscle and
      advised patients to perform early exercise of the posterior neck muscle. The
      patients who had the original operation and postoperative therapy served as the
      control (control group). The original operation and postoperative therapy were as
      follows: Bone grafts from dissected spinous processes were put in the opened
      laminae and fixed with braided wires or nylon threads. Bone grafts in the open
      gap were placed to extend from three to five levels. Bone chips were also placed
      in the hinged side. The orthosis was applied for up to 1 months after surgery,
      and a neck collar was recommended for 1 additional month. Postoperative
      neurologic recovery and axial symptoms after cervical laminoplasty were compared
      between the two groups. There was no statistical difference in postoperative
      neurologic recovery. However, the incidence of axial symptoms was much lower in
      the modified group compared with the control group. Radiologic examination showed
      that postoperative range of motion of the cervical spine in the modified group
      was significantly well preserved and the number of postoperative fused laminae in
      the modified group was less than that in the control group. Based on these
      results, we concluded that the modified method is beneficial for the
      postoperative status of cervical laminoplasty patients.

PMID- 14657745
TI  - Perioperative complications of threaded cylindrical lumbar interbody fusion
      devices: anterior versus posterior approach.
AB  - Few data are available to evaluate approach-related differences in perioperative
      complications with lumbar interbody fusion devices. Complications occurring in
      the intraoperative and immediate postoperative period were identified and
      categorized for 31 consecutive posterior lumbar interbody fusions (PLIFs) and 88
      consecutive anterior lumbar interbody fusions (ALIFs). In this study, all lumbar
      interbody fusions were conducted with threaded cylindrical devices as stand-alone
      internal fixation devices. Multivariate analysis was used to account for
      potential covariates and identify factors associated with an increased
      complication risk. Twenty-two percent of the patients had a perioperative
      complication. The relative risk of having a perioperative complication was 4.75
      times higher for the PLIF group. All intraoperative complications occurred in the
      PLIF group. The relative risk of having a major postoperative complication was
      6.8 times higher in the PLIF group than the ALIF group. Anterior approached
      patients tended to have visceral (ileus, 6%) and vascular (deep venous
      thrombosis, 2%) complications. In the posterior group, complications were
      neurologic and dura related (pseudomeningocele, 16%; epidural hematoma, 3%) and
      occurred most frequently in patients that had had previous posterior lumbar
      surgery (31% with major complication).

PMID- 14657746
TI  - The use of postoperative subcutaneous closed suction drainage after posterior
      spinal fusion in adolescents with idiopathic scoliosis.
AB  - BACKGROUND The purpose of this prospective study was to assess the impact of
      closed suction drainage on transfusion requirements, frequency of dressing
      changes, and wound healing following posterior spinal fusion in adolescents with
      idiopathic scoliosis. METHODS Thirty patients were randomly assigned to one of
      two groups: drain or no drain. Although the group with drains received more
      postoperative autologous blood transfusions than the group with no drains (0.88
      vs 0.5 unit), the difference was not statistically significant (P = 0.2131). In
      the undrained group, 58% of the patients had moderate to completely saturated
      dressings on the second postoperative day compared with only 17% of patients in
      the drained group. Three of 12 patients in the undrained group demonstrated a
      wound complication rate compared with no complications in the drained group.
      CONCLUSION In conclusion, subcutaneous closed suction drainage can improve
      immediate postoperative wound care without significantly increasing blood loss
      and transfusion requirements for patients undergoing surgery for idiopathic
      scoliosis.

PMID- 14657747
TI  - Pitfalls of anterior cervical fusion using titanium mesh and local autograft.
AB  - Cervical fusion cages have been developed to provide an anterior structural
      support without harvesting tricortical iliac bone. Limited numbers of
      investigations have focused on pitfalls of anterior cervical fusion using cage
      implants. The objective of this study is to report clinical results and implant
      related complications in anterior cervical fusion using titanium mesh and
      anterior plating. Twenty-four cases with anterior cervical fusion using a
      titanium mesh with local autograft and anterior plating were reviewed. One-level
      fusion was performed in 7 cases, and 17 patients underwent two-level fusion with
      corpectomy. The mean follow-up period was 27 months. Radiographic assessment
      included sagittal alignment, fusion status, and complications related to cage
      implants. Iliac bone graft harvesting was obviated in all the patients, whereas
      15 patients required concomitant use of ceramic bone substitute. Sagittal
      alignment of the operative level was lordotic in 19 cases (79%) and neutral in 5
      cases (21%) at the final follow-up. No late kyphotic collapse was observed.
      Twenty-three cases (96%) achieved a solid fusion, whereas the time to fusion was
      averaged 6.2 months. Cage subsidence frequently occurred in 42% of upper
      vertebrae and 50% of lower vertebrae. The use of titanium mesh and local
      autograft for anterior cervical fusion obviated the need for harvesting iliac
      bone block and provided structural anterior column support. However, it required
      a longer period to achieve a solid fusion when compared with tricortical iliac
      autograft. Cage subsidence was frequently observed in the early postoperative
      period.

PMID- 14657748
TI  - Delayed esophageal injury without instrumentation failure: complication of
      anterior cervical instrumentation.
AB  - The authors describe a case of a 67-year-old man who presented with a delayed
      esophageal perforation 4 years after anterior cervical spine surgery for
      spondylotic myelopathy. Diagnosis was made with esophagoscopic visualization of
      the lesion and repair performed with hardware removal and esophageal closure
      utilizing a sternocleidomastoid muscle flap. The pertinent literature is reviewed
      and the therapeutic implications discussed.

PMID- 14657749
TI  - Acute traumatic L5-S1 spondylolisthesis.
AB  - Acute traumatic L5-S1 spondylolisthesis is a rare condition, almost exclusively
      the result of major trauma, frequently associated with L5 transverse process
      fracture and neurologic deficit. In recent years, open reduction and internal
      fixation with posterior stabilization has been the method of treatment most
      frequently reported. In the current case, the lesion was found in a victim of an
      automobile accident. Signs of a right L5 root deficit but no sphincter
      dysfunction were present. A computed tomography scan revealed several fractures
      in the posterior parts of L5 and anterior displacement of L5 on S1. A magnetic
      resonance imaging (MRI) scan verified that the lesion was indeed acute by showing
      the ruptured L5 disc and posterior ligaments, thereby demonstrating the
      importance of MRI in the planning of the treatment of these lesions. This case
      was successfully treated with an acute circumferential instrumented L4-S1
      spondylodesis.

PMID- 14657750
TI  - Posterior releasing techniques for idiopathic scoliosis: microscopic discectomy
      and transverse process resection: a technical note.
AB  - The authors describe techniques and preliminary results of two releasing
      procedures for idiopathic scoliosis, which can be performed concomitantly in the
      same stage of posterior instrumentation surgery. The transpedicular microscopic
      discectomy and transverse process resection were clinically applied for
      adolescent idiopathic scoliosis. Twelve patients were divided into three groups
      at random: Group A patients underwent no release, group B patients underwent
      transverse process resection, and group C patients underwent microscopic
      discectomy of three discs and transverse process resection, in combination. All
      patients were operated on with derotation procedure with Cotrel-Dubousset
      instrumentation simultaneously after each releasing procedure. The outcomes-curve
      correction, disc wedge angle, and rotational changes-were evaluated 12 months
      postoperatively. The mean correction rate of the Cobb angle in group C (78%) was
      higher than in groups A (54%) and B (64%). Correction of the disc wedge angle was
      also higher in group C compared with groups A and B. The authors conclude that
      microscopic discectomy appeared to be an effective releasing method for thoracic
      curve and that further investigation is necessary for accurate evaluation of the
      transverse process resection.

PMID- 14657751
TI  - Extraforaminal lumbar herniation: "far lateral" microinvasive approach
      retrospective study.
AB  - The first anatomic description of extraforaminal herniation found in the
      literature was published in 1944. This was followed by several definitions
      regarding the anatomic site of this pathology. We consider correct the definition
      of lumbar extraforaminal herniation concerning the anatomic site of the herniated
      fragment. This fragment compresses the nervous root after its exit from the
      foramen, thus causing the compression of the spinal ganglion against the strong
      intertransverse ligament. The incidence of the pathology shifts from 1% to 12%
      and in our study was 4.2%. Over these years, the surgical approach has changed
      mainly because of two requirements: good exposition both of the foramen and of
      the herniation and the necessity of preserving stability of the spinal column as
      much as possible. In the last 30 years, less invasive approaches, paramedian,
      para- and transmuscular, lateral, and tangential, have been preferred to an
      interlaminar medial approach with a subtotal and/or complete facetectomy. In the
      last 4 years, 46 patients presenting with pure extraforaminal herniation have
      been treated in our institute through a far lateral microsurgical approach,
      avoiding resection of bone and reducing to the minimum the muscular retraction
      and the closure of blood vessels. We advocate a far lateral microsurgical
      approach, with no resection of bone and with highest respect for the osseous
      articular and muscular structures.

PMID- 14657752
TI  - Safer injection of cervical nerve roots.

PMID- 14657753
TI  - Phagocytic efficiency of monocytes and macrophages obtained from Sydney blood
      bank cohort members infected with an attenuated strain of HIV-1.
AB  - Defective function of monocyte-derived macrophages contributes to HIV-1
      pathogenesis. We found that phagocytosis of the opportunistic pathogens
      Mycobacterium avium complex and Toxoplasma gondii was impaired in monocytes
      obtained from individuals infected with wild-type strains of HIV-1 but generally
      not in monocytes collected over a 6-year period from Sydney Blood Bank Cohort
      (SBBC) members infected with nef/long terminal repeats (LTR) region-defective
      strains of HIV-1. However, longitudinal analysis of phagocytosis in 1 SBBC
      member, C54, showed the development of defective engulfment of opportunistic
      pathogens at the most recent time points, coincident with the development of
      further molecular deletions in the nef/LTR region. Another SBBC member, C98,
      underwent bronchoscopy, which provided material to examine phagocytic signaling
      in alveolar macrophages. In contrast to normal phagocytic efficiency of C98's
      monocytes (over a 6-year period), defective signaling events during FcgammaR
      mediated phagocytosis by C98's alveolar macrophages were observed. High basal
      phosphorylation within HIV-infected macrophages correlated with colocalization of
      tyrosine-phosphorylated proteins with HIV-1 p24 antigen rather than around the
      phagocytic targets as observed in uninfected cells. Thus, although phagocytic
      efficiency appears to be generally unimpaired in monocytes from SBBC members,
      evidence of impairment in recent samples from 1 SBBC member, coincident with
      further genetic changes within the virus, and abnormal phagocytic signaling in
      alveolar macrophages from another SBBC member may herald loss of attenuation of
      those strains.

PMID- 14657754
TI  - HIV-1 infection in a small animal human vaginal xenograft model.
AB  - A limitation in advancing the study of HIV-1 is the lack of a suitable small
      animal model system that allows for HIV-1 infection to be monitored within human
      target epithelium. Studies have demonstrated that HIV-1 can infect vaginal mucosa
      after sexual exposure; however, the primary target cells for HIV-1 in the vagina
      and interactions between these target cells are not completely defined. A mouse
      human vaginal xenograft model that recapitulates, histologically and
      cytochemically, the features of the human vaginal epithelial barrier has been
      developed in our laboratory. Results of experiments utilizing this system to
      characterize HIV-1 BaL and IIIB infections within human vaginal xenografts are
      reported here. HIV-1 RNA, spliced transcripts, and HIV-1 p24 core antigen protein
      were detected in the xenografts 7 days after infection. This unique system offers
      a small animal model for studying HIV-1 transmission and replication within the
      context of natural host tissue and for examining initial events and cell
      populations involved in the establishment of HIV-1 infection.

PMID- 14657755
TI  - Incidence of lipoatrophy and lipohypertrophy in the women's interagency HIV
      study.
AB  - OBJECTIVE: To estimate the incidence of lipoatrophy and lipohypertrophy among HIV
      infected and HIV-uninfected women from the Women's Interagency HIV Study. DESIGN:
      Eight hundred fifteen women with semiannual data on self-report of bidirectional
      change in body fat, anthropometric measurements, weight, and bioelectric
      impedance analysis were included in a 30-month incidence analysis. METHODS:
      Lipoatrophy and lipohypertrophy in both peripheral (arms, legs, and buttocks) and
      central (waist, chest, and upper back) sites were defined by self-report of
      either a decrease or an increase in a body fat region over the previous 6 months
      that was confirmed by a corresponding change in anthropometric measurement.
      RESULTS: Weight and total body fat increased in HIV-uninfected women but remained
      stable in HIV-infected women over 30 months. Among HIV-infected women, the
      incidence of peripheral (relative hazard, 2.1; 95% confidence interval [CI], 1.4
      3.3) and central (relative hazard, 1.9; 95% CI, 1.2-2.8) lipoatrophy was about
      double that among HIV-uninfected women, after adjustment for age and race. The
      incidence of peripheral lipohypertrophy appeared lower among HIV-infected women
      than among HIV-uninfected women (relative hazard, 0.8; 95% CI, 0.6-1.1), while
      the incidence of central lipohypertrophy did not differ by HIV status. Of HIV
      infected women with 2 of 4 lipodystrophy outcomes, most (81%) had combined
      peripheral and central lipoatrophy or combined peripheral and central
      lipohypertrophy. Only 14% of these women had both peripheral lipoatrophy and
      central lipohypertrophy. CONCLUSIONS: These prospective data suggest that
      lipoatrophy, affecting both peripheral and central sites, predominates in HIV
      infected women. The simultaneous occurrence of peripheral lipoatrophy and central
      lipohypertrophy was uncommon.

PMID- 14657756
TI  - Patterns of selective neuronal damage in methamphetamine-user AIDS patients.
AB  - The risk for HIV infection attributable to methamphetamine (METH) use continues
      to increase. The combined effect of HIV and METH in the pathogenesis of HIV
      encephalitis (HIVE) is unclear, however. To better understand the neuropathology
      associated with HIV and METH use, the patterns of neurodegeneration were assessed
      in HIV-positive METH users and in HIV-positive non-METH users. Patients in the
      study met criteria for inclusion and received neuromedical and postmortem
      neuropathologic examinations. Immunocytochemical and polymerase chain reaction
      analyses were performed to determine brain HIV levels and to exclude the presence
      of other viruses. METH-using patients with HIVE showed significantly lower gp41
      scores and less severe forms of encephalitis but a higher frequency of ischemic
      events, a more pronounced loss of synaptophysin immunoreactivity, and a more
      severe microglial reaction than HIVE non-METH users. Furthermore, in METH-using
      patients with HIVE, extensive loss of calbindin (CB)-immunoreactive interneurons
      displaying phylopodial neuritic processes suggestive of aberrant sprouting was
      observed. Taken together, these studies indicate that the combined effects of
      METH and HIV selectively damage CB immunoreactive nonpyramidal neurons. In
      combination, METH and HIV may increase neuronal cell injury and death, thereby
      enhancing brain metabolic disturbances observed in clinical populations of HIV
      positive METH abusers.

PMID- 14657757
TI  - Changes in CD4+ T-cell differentiation phenotype during structured treatment
      interruption in patients with chronic HIV-1 infection.
AB  - Markers of maturation and activation were measured on peripheral CD4+ T cells in
      chronically HIV-1-infected patients in a randomized, controlled pilot study of
      structured treatment interruption (STI). Eight subjects underwent 2 cycles of 1
      month off and 1 month on highly active antiretroviral therapy (HAART), followed
      by a final 3-month interruption. During STI, CD4+ T-cell percentage remained
      relatively stable in 4 of 8 subjects. The remaining 4 STI subjects had
      significant rapid decline in CD4+ T-cell percentage during STI, followed by
      return to pre-STI baseline while on HAART. Changes in overall CD4+ T-cell
      percentage corresponded with fluctuations in the CD45RA+CCR7+ naive and CD45RA
      CCR7+ central memory subsets. Subjects with variable CD4+ T-cell percentages
      tended to have higher pre-HAART plasma HIV-1 RNA set-points and experienced
      higher levels of plasma HIV-1 RNA rebound during STI. These results suggest that
      interruptions should be avoided whenever possible in patients on HAART with high
      plasma HIV-1 RNA set-points.

PMID- 14657758
TI  - Safety and trough concentrations of nevirapine prophylaxis given daily, twice
      weekly, or weekly in breast-feeding infants from birth to 6 months.
AB  - Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV
      1 transmission, postpartum transmission through breast milk remains a problem.
      Antiretroviral administration to the infant during the period of breast-feeding
      could protect against postnatal transmission. An open-label phase 1/2 study was
      designed to assess the safety and trough concentrations of nevirapine (NVP) given
      once weekly (OW), twice weekly (TW), or once daily (OD) to HIV-exposed breast
      feeding infants for 24 weeks. Following maternal dosing with 200 mg NVP orally at
      onset of labor, breast-feeding infants were randomized within 48 hours of birth
      to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, upward
      arrow to 8 mg/kg from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from
      birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), and arm 3,
      NVP given OD (2 mg/kg from birth to 14 days, upward arrow to 4 mg/kg from 15 days
      to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities
      were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD
      dosing), 63 completed the 32-week follow-up visit. No severe skin, hepatic, or
      renal toxicity related to NVP was observed. Neutropenia occurred in 8 infants.
      Trough NVP levels were lower than the therapeutic target (100 ng/mL) in 48 of 75
      (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm,
      and 0 of 72 samples in the OD arm. Median (range) trough NVP concentrations were
      64 ng/mL (range: <25-1519 ng/mL) with OW dosing; 459 (range: <25-1386 ng/mL) with
      TW dosing; and 1348 (range: 108-4843 ng/ml) with OD dosing. Our data indicate
      that NVP prophylaxis for 6 months was safe and well tolerated in infants. OD NVP
      dosing resulted in all infants with trough concentration greater than the
      therapeutic target and maintenance of high drug concentrations. A phase 3 study
      is planned to assess the efficacy of OD infant NVP regimen to prevent breast
      feeding HIV-1 transmission.

PMID- 14657759
TI  - HIV-1-infected antiretroviral-treated patients with prolonged partial viral
      suppression: clinical, virologic, and immunologic course.
AB  - The long-term feasibility of a drug conservation strategy that allows low-level
      viral replication is unknown. We performed a retrospective study of treated HIV
      infected patients with stable detectable viral replication (<10000 copies/mL [low
      level viremia]) and compared their clinical, virologic and immunologic courses
      with those of treated patients with undetectable viremia and viremia (>or=10000
      copies/mL [high-level viremia]). Viral reverse transcriptase and protease
      genotype and HIV-specific CD4 T-cell responses were determined using patient
      derived samples. Clinical and immunologic benefits were maintained in patients
      with partial virologic suppression (<or=10000 copies/mL). Although low-level
      viral replication under drug pressure led to the accumulation of resistance
      mutations in most subjects' viruses, most subjects retained susceptibility to
      drugs in >or=2 classes of antiretroviral medications. HIV-specific CD4+ T-cell
      immunity was detected in most subjects with low-level and undetectable viremia
      and may have a role in controlling viremia in the setting of partial suppression.

PMID- 14657760
TI  - Plasma levels of indinavir and nelfinavir at time of virologic response may have
      a different impact on the risk of further virologic failure in HIV-infected
      patients.
AB  - Indinavir and nelfinavir plasma levels were studied in 407 patients having plasma
      HIV RNA <500 copies/mL after 4 months of treatment with these drugs. For each
      drug, an observed/predicted (O/P) ratio was calculated between individual and
      mean time-adjusted population plasma drug levels. The relationship between the
      O/P ratio and the risk of rebound of plasma HIV RNA >500 copies/mL beyond month 4
      was studied using Cox proportional hazard models. Median follow-up was 20 months.
      There was no association between indinavir plasma levels and risk of virologic
      rebound, whereas low nelfinavir + M8 (active nelfinavir metabolite) plasma levels
      were associated with a higher risk of virologic rebound. In multivariate
      analysis, the adjusted relative hazard of virologic rebound for patients with an
      O/P ratio of nelfinavir + M8 metabolite <0.8 compared with others was 2.2 (P =
      0.01). In some patients, plasma levels of nelfinavir sufficient to achieve early
      viral response may not be sufficient to maintain it in the long term. This may be
      related to insufficient compliance with dietary recommendations. Monitoring of
      nelfinavir plasma levels thus seems useful, even in patients having early
      virologic response.

PMID- 14657761
TI  - Human herpesvirus 8 infection among various population groups in southern Israel.
AB  - OBJECTIVE: To compare the prevalence of antibodies to human herpesvirus 8 (HHV-8)
      or Kaposi sarcoma-associated herpesvirus among Israeli and Ethiopian subjects.
      METHODS: Serum samples were obtained from 98 Israeli Jewish students aged 18-30
      years, 100 HIV-1-seronegative Ethiopian immigrants to Israel of the same age, and
      100 HIV-1-seronegative Ethiopian children 1-12 years old upon their arrival in
      southern Israel. Plasma samples were obtained from 3 hospitalized patients with
      multicentric Castleman disease (MCD) as positive controls. All serum samples were
      tested for antibodies to both latent and lytic antigens. Antibodies to the lytic
      antigens and the latency-associated nuclear antigen (LANA) of HHV-8 were detected
      by enzyme linked immunosorbent assay and by immunofluorescence assay. HHV-8 DNA
      from serum or plasma samples was detected by polymerase chain reaction analysis.
      RESULTS: Antibodies to HHV-8 LANA were detected in 2.9% of the Israeli subjects
      aged 18-30 years and in 26% of the Ethiopian subjects from both age groups
      tested. Antibodies to the lytic antigens were detected in all 3 MCD patients, in
      4% of the Ethiopian children, and in 2% of the 18- to 30-year-old Ethiopians. No
      antibodies to the lytic antigens were detected in the Israeli students. HHV-8 DNA
      was detected in all 3 MCD patients and in 2 of 4 of the Ethiopian children
      positive for the lytic antigens. CONCLUSIONS: HHV-8 is highly prevalent in
      Ethiopian immigrants to Israel as compared with Israeli students. Antibodies to
      HHV-8 in Ethiopia are acquired before puberty. The results of this study indicate
      the association of HHV-8 with MCD, as has been documented by many other
      researchers.

PMID- 14657762
TI  - Preventing mother-to-child HIV transmission in a developing country: the
      Dominican Republic experience.
AB  - Transmission of HIV in the Dominican Republic occurs primarily through
      heterosexual contact. As part of a continuing strategy to prevent and contain the
      spread of HIV infection, the Ministry of Health of the Dominican Republic
      established an integrated package of interventions to reduce HIV mother-to-child
      transmission that was initiated on May 15, 2000. The program was designed to be
      implemented in 3 phases. The 1st phase included 4 mother and child hospitals; the
      2nd phase included 8 mother and child health institutions in Santo Domingo, the
      capital of the Dominican Republic, and 7 additional mother and child hospitals.
      The 3rd phase will include the remaining 12 mother and child health care
      institutions of the Dominican Republic. Evaluation of the 1st year of this
      program, involving 8 hospitals and >40000 pregnant women, identified specific
      benefits and limitations. Low numbers of voluntary counseling sessions
      (6528/42666 = 28%) and inadequate number of HIV rapid tests (23067/42666 = 54%)
      were the 2 main obstacles encountered. From the 23067 pregnant women tested, 581
      (2.5%) were HIV positive. Advantageous aspects included the successful
      administration of antiretroviral treatment to 89% (164/185) of the mothers and
      98% (183/186) of the children. Cesarean section was performed in 67% (124/185) of
      the HIV-positive pregnant women, and infant formula was dispensed to 47% (87/186)
      of all cases. These findings demonstrate the feasibility of implementing a large
      scale program to prevent mother-to-child transmission in a developing country.

PMID- 14657763
TI  - Performance characteristics of HIV-1 culture and HIV-1 DNA and RNA amplification
      assays for early diagnosis of perinatal HIV-1 infection.
AB  - A plasma HIV-1 RNA amplification assay (RNA assay), a quantitative peripheral
      blood mononuclear cell (PBMC) microculture (culture), and a PBMC HIV-1 DNA
      amplification assay (DNA assay) were compared for diagnosis of HIV-1 infection in
      infants receiving zidovudine in Pediatric AIDS Clinical Trials Group protocol
      185; assays were performed for all 24 infected and 100 uninfected infants. HIV-1
      infection was defined as >or=2 positive cultures or positive antibody to HIV-1 at
      >or=18 months. Cultures were performed at birth and 6 and 24 weeks of age; DNA
      and RNA assays were performed on cryopreserved specimens. The sensitivity of
      culture and DNA and RNA assays at birth was 20.8%, 10.5%, and 26.7%,
      respectively. At older ages, sensitivity typically exceeded 80%, remaining
      highest for the RNA assay (>85%). Assay specificity was >99%. Positive predictive
      values exceeded 93% for each assay at each age; negative predictive values were
      highest (>90%) for the RNA assay. At birth (P < 0.005) and age 6 weeks (P <
      0.001), a significantly larger proportion of infected infants were identified by
      means of the RNA assay than by the other assays. The diagnostic performance of
      the RNA assay matched or exceeded that of culture and the DNA assay. Given that
      RNA assays require less blood volume and yield rapid results, our study adds to
      existing data suggesting that RNA assays may be used for early diagnosis of HIV-1
      infection in infants.

PMID- 14657764
TI  - Epidemiologic and molecular characterization of human immunodeficiency virus type
      1 in southern Brazil.
AB  - HIV subtype C is the most prevalent subtype in the world. Despite its recent
      expansion in Brazil, HIV-1C already prevails in the southernmost state of Brazil,
      Rio Grande do Sul. This unique HIV epidemiology has prompted us to characterize
      that population. Seventy-seven HIV-1-infected subjects attending the largest
      HIV/AIDS clinic of the state had the protease and reverse transcriptase (RT)
      genes of their virus subtyped and genotyped. When subtype-specific infections
      were plotted according to year of diagnosis, the prevalence of subtype C was
      shown to increase over the last 18 years of the epidemic, along with a
      concomitant decrease of subtype B. Comparison of subtype C-infected treated and
      untreated subjects revealed amino acid differences in protease and RT, especially
      in the RT mutation D/G123S. The overall analysis of drug resistance mutations in
      viruses from treated subjects has highlighted some associations between subtypes
      and particular mutations, such as V82A/F/T/S in protease and subtype F1 and M41L
      and L210W in RT and subtype B. The characterization of this important population,
      which is one of a few in the developing world where a large number of HIV-1C
      infected subjects are under antiretroviral treatment, underscores its potential
      usefulness in clinical, treatment, and vaccine trials in Brazil.

PMID- 14657765
TI  - HTLV-I in the general population of Salvador, Brazil: a city with African ethnic
      and sociodemographic characteristics.
AB  - The city of Salvador has the highest prevalence of HTLV-I among blood donors in
      Brazil. To study the prevalence of HTLV-I among the general population of
      Salvador, 30 "sentinel surveillance areas" were selected for the investigation of
      various infectious diseases, and 1385 individuals within these areas were
      surveyed according to a simple random sample procedure. ELISA was used to screen
      plasma samples for antibodies to HTLV-I, and the positive samples were tested by
      a confirmatory assay (Western blotting). The overall prevalence of HTLV-I was
      1.76% (23/1385). Infection rates were 1.2% for males and 2.0% for females.
      Specific prevalence demonstrated an increasing linear trend with age. No one
      younger than 13 years of age was infected. Multivariate analysis estimated
      adjusted odds ratios for the association of HTLV-I with age of 9.7 (3.3; 30.4)
      for females and 12.3 (1.47; 103.1) for males. Less education and income might be
      associated with HTLV-I infection in females. Phylogenetic analysis of the long
      terminal repeat fragments showed that most of the samples belonged to the Latin
      American cluster of the Transcontinental subgroup (Cosmopolitan subtype). For the
      entire city of Salvador, it is estimated that approximately 40000 individuals are
      infected with HTLV-I. Our results suggest multiple post-Colombian introductions
      of African HTLV-Ia strains in Salvador.

PMID- 14657766
TI  - Nonnucleoside reverse transcriptase inhibitor-containing regimens are associated
      with increased satisfaction with sexual life.

PMID- 14657767
TI  - Alanine aminotransferase levels predict insulin resistance in HIV lipodystrophy.

PMID- 14657769
TI  - Raised plasma levels of tumor necrosis factor alpha in patients with depression:
      normalization during electroconvulsive therapy.
AB  - OBJECTIVE: To examine whether electroconvulsive therapy (ECT) could modulate
      tumor necrosis factor (TNF)alpha levels in patients with depressive disorders.
      METHOD: Plasma levels of TNFalpha were analyzed in 23 depressed patients, mainly
      with severe depressive disorders, and in 15 sex- and age-matched healthy
      controls. Fifteen depressed patients were followed longitudinally with
      measurement of TNFalpha before, during, and after repeated ECT treatment. For
      comparison, TNFalpha levels were also analyzed longitudinally in the 8 depressed
      patients not receiving ECT. RESULTS: Patients with depressive disorders had
      markedly raised TNFalpha levels compared with healthy controls. The clinical
      improvement during repeated ECT was accompanied by a gradual and significant
      decline in TNFalpha level, reaching levels comparable with those in healthy
      controls at the end of the study. Such a decline was not seen in the depressed
      patients not receiving ECT, who instead showed raised TNFalpha levels throughout
      the study period. CONCLUSION: Our findings support an association between
      inflammation and TNFalpha in particular and severe depression, and suggest that
      ECT may down-regulate this immune activation.

PMID- 14657770
TI  - Seizures induced by low-dose right unilateral and bifrontal electroconvulsive
      stimuli.
AB  - The duration of electroconvulsive therapy (ECT) seizures of depressive patients
      has been found to be inversely related to titrated right unilateral (RUL) and
      bilateral (BL) seizure threshold (ST) levels. This inverse relationship is
      thought to reflect those neural processes determining seizure duration. The
      relation between seizure duration and titrated ST level in bifrontal (BF) ECT,
      which has not been previously studied, is examined here in addition to RUL ECT.
      We found an inverse relationship in RUL ECT but no relationship in BF ECT.
      Eighteen percent of RUL patients seized at the first stimulus level versus 40% of
      BF patients. Compared with previous studies, both our starting dose and the
      increments between stimuli were greater in BF ECT (50.4 mC) than in RUL ECT (25.2
      mC). A relationship between stimulus dose and seizure length may have also been
      present in BF ECT had similar titration schedules been used for both electrode
      placements. Future studies using titration schedules with a lower initial dose
      and finer gradations between stimulus levels are needed to evaluate whether a
      relationship between stimulus dose and seizure duration exists in BF ECT.

PMID- 14657771
TI  - Transcutaneous acupoint electrical stimulation in preventing and treating nausea
      and vomiting in patients receiving electroconvulsive therapy.
AB  - A significant number of patients complain of nausea after general anesthesia and
      electroconvulsive therapy (ECT). Nausea is second only to headache as the most
      frequent and troublesome systemic side effect of ECT. The most common treatment
      of this is antiemetic drugs. Transcutaneous acupoint electrical stimulation
      (TAES) is a nonpharmacologic method for preventing and treating nausea and
      vomiting. TAES can alleviate motion sickness, reduce the incidence of vomiting
      caused by chemotherapy, and treat pregnancy-induced nausea and vomiting. TAES has
      been shown to reduce the incidence of postoperative nausea after general
      anesthesia. This is the first report to review the effectiveness of TAES in
      preventing and treating nausea and vomiting in 11 patients receiving ECT. Nine of
      these patients had a good response to TAES. One patient had a mixed response, and
      1 did not respond to TAES.

PMID- 14657772
TI  - Spectral EEG effects of electroconvulsive shock stimulus parameters: the
      development of a rationale for the optimization of the ECT stimulus.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) stimulus parameters, such as pulse
      amplitude, pulse width, pulse frequency, and stimulus duration, differently
      influence seizure threshold and, possibly, other neurobiological effects of ECT.
      We examined the influence of these parameters on the EEG power spectrum in an
      animal model. METHODS: Adult, male, Wistar rats (n=54) were randomized to receive
      one of five differently constituted (approximately) 30-mC electroconvulsive shock
      (ECS) stimuli administered once on alternate days for a total of three ECS. A
      single-lead, unipolar EEG recording was obtained before, during, and immediately
      after each ECS seizure. EEG power was computed in eight frequency bands from 2 to
      40 Hz. Greater ictal EEG power, greater postictal EEG suppression, and greater
      interictal EEG power, especially in lower frequency bands, were a priori defined
      as proxies of seizure efficacy. RESULTS: Motor and EEG seizure duration and a
      proxy for seizure generalization did not differ significantly across the five
      stimulus groups. Despite equivalent charge, the five stimuli varied widely in
      their effects on the EEG proxies of seizure efficacy. The narrow (0.6
      milliseconds) pulse width, high (100 Hz) pulse frequency combination was best
      associated with EEG proxies of seizure efficacy; with this combination, a longer
      stimulus train duration appeared superior to a greater pulse amplitude. The wide
      (2 milliseconds) pulse and low (30 Hz) frequency combination was least associated
      with EEG proxies of efficacy. Stimulus "on" time, number of pulses delivered, and
      the rate of delivery of charge were not associated with the EEG proxies; the
      former finding questions the validity of dosing ECT in units of charge.
      CONCLUSIONS: These findings suggest a rationale for optimizing stimulus parameter
      choices during ECT and provide a framework for the evaluation of electrical
      aspects of the ECT stimulus.

PMID- 14657773
TI  - Benefits of the laryngeal mask for airway management during electroconvulsive
      therapy.
AB  - Accumulation of carbon dioxide (CO2) can disturb systemic hemodynamics and
      increase the seizure threshold in patients receiving electroconvulsive therapy
      (ECT). The purpose of this study was to investigate the effects of the laryngeal
      mask on blood gas, hemodynamics, and seizure duration during ECT under propofol
      anesthesia. Ventilation was assisted using either a face mask (n=23) or laryngeal
      mask (n=23) and 100% oxygen. There was no significant difference in PaO2 between
      the two groups. PaCO2 was greater in the face mask group than the laryngeal mask
      group at 3 minutes (54 +/- 11 mm Hg, 41 +/- 8 mm Hg, respectively) and 5 minutes
      (52 +/- 11 mm Hg, 43 +/- 15 mm Hg, respectively) after electrical stimulation
      (p<0.01). Mean blood pressure was higher than the corresponding preanesthesia
      value at 1 to 5 minutes after electrical stimulation in the face mask group and
      at 1 to 3 minutes after electrical stimulation in the laryngeal mask group. Mean
      seizure duration in the face mask group was significantly shorter than that in
      the laryngeal mask group (33 +/- 11 seconds, 42 +/- 10 seconds, respectively
      p<0.01). The change in PaCO2 was minor in the laryngeal mask group compared with
      the face mask group and seizure duration was longer in the laryngeal mask group.
      Laryngeal mask may be suitable for airway management during ECT anesthesia,
      especially when fitting a face mask is difficult.

PMID- 14657774
TI  - Electroconvulsive therapy clinics in the United Kingdom should routinely monitor
      electroencephalographic seizures.
AB  - Information recorded during electroconvulsive therapy for all patients treated in
      Central Manchester was analyzed to examine the range of seizure thresholds, the
      frequency of prolonged seizures, and the difference between the length of motor
      and electroencephalographic seizure activity. Prolonged seizures occurred in 19%
      of courses studied. EEG seizure length was significantly longer than observed
      motor seizure length. EEG monitoring will detect prolonged seizures and should be
      performed routinely in ECT clinics in the United Kingdom.

PMID- 14657775
TI  - The comparative effects of sevoflurane and methohexital for electroconvulsive
      therapy.
AB  - The standard anesthetic agent for electroconvulsive therapy (ECT) has been
      methohexital. We compared sevoflurane, a short-acting halogenated anesthetic, to
      methohexital for induction in ECT. Twelve subjects received sevoflurane or
      methohexital on alternating treatment days. Seizure duration, time to
      administering ECT, emergence and recovery, as well as several hemodynamic
      measures were recorded. A total of 69 treatments were analyzed. When sevoflurane
      was used, seizure durations recorded by observation and by EEG, were shorter by
      10 and 23 seconds, respectively. With sevoflurane, seizure duration remained,
      however, within a clinically acceptable range. Methohexital allowed faster
      administration of ECT and discharge from the recovery room (3.8 vs. 6.2 minutes
      and 40.8 vs. 47.0 minutes, respectively). No difference in the post-ECT
      hemodynamic changes was found between the two treatments. We conclude that, when
      indicated, sevoflurane could provide a suitable alternative treatment option to
      methohexital, but some limitations, including shortened seizure duration and
      potential side effects, should be kept in mind.

PMID- 14657776
TI  - Electroconvulsive therapy in complex regional pain syndromes.
AB  - Three cases are presented in which electroconvulsive therapy (ECT) for depression
      led to the relief of comorbid complex regional pain syndrome as well as
      depression. In one of the cases, concomitant fibromyalgia was not relieved during
      2 separate series of ECT. The literature regarding the role of ECT in the
      management of chronic pain is reviewed and discussed in light of recent findings
      about ECT and changes in neurotransmission associated with seizures.

PMID- 14657777
TI  - Safe ECT in a patient with the Ehlers-Danlos syndrome.
AB  - The Ehlers-Danlos syndrome is an inheritable disorder caused by genetic defects
      of collagen. Hyperextensibility and fragility of the skin, joint hyperlaxity, and
      generalized fragility of the connective tissues, involving the hollow organs and
      arteries, are the cardinal features of this syndrome. Low bone density has also
      been reported. Theoretically, these patients can have an increased risk of
      rupture of blood vessels and of bone fractures. A patient with a schizo-affective
      disorder and Ehlers-Danlos Type I who received bifrontal ECT for a depressive
      episode is described. Even without specific measures to lower blood pressure, a
      course of ECT was finished without any complication.

PMID- 14657778
TI  - Use of ECT in idiopathic intracranial hypertension.
AB  - In 2001 the Second Edition of the American Psychiatric Association's Task Force
      Report on ECT maintained that no absolute contraindications to ECT exist. They
      warned, however, that ECT in persons with elevated intracranial pressure should
      be considered on a case-by-case risk to benefit ratio. Literature on the use of
      ECT in patients with elevated intracranial pressures is limited to space
      occupying lesions as a cause for elevated pressures. This case report presents a
      42-year-old woman with treatment-refractory major depression and idiopathic
      intracranial hypertension (also known as pseudotumor cerebri). Brain imaging and
      lumbar puncture were performed before ECT, and blood pressures were monitored
      closely during treatment. Treatment was successful with minimal adverse effects.
      With appropriate clinical observation, patients with idiopathic intracranial
      hypertension can be considered for ECT.

PMID- 14657779
TI  - ECT resistance and early relapse: two cases of subsequent response to
      venlafaxine.
AB  - Many depressed patients who fail to respond to numerous trials of antidepressant
      medications are ultimately referred for electroconvulsive therapy (ECT). However,
      a complete response does not occur in all depressed patients referred for ECT.
      The erroneous portrayal of ECT as a 'last ditch' treatment of depression leads to
      predictable despair if ECT fails or if early relapse occurs after a brief
      response. Therapeutic nihilism is not warranted in these cases. There is evidence
      in the literature that patients who fail to respond to adequate trials of
      antidepressant medications prior to ECT failure or early relapse subsequently
      respond to psychopharmacological treatment with high doses of venlafaxine. The
      following two case reports provide examples of depressed patients who
      subsequently responded to high doses of venlafaxine after demonstrating
      resistance to ECT, or experiencing rapid relapse after successful ECT.

PMID- 14657780
TI  - Aortic aneurysm and electroconvulsive therapy in elderly depressive patient.
AB  - We report the case of a 67-year-old single man with aortic aneurysm whose
      depression was successfully treated with electroconvulsive therapy. Metoprolol
      succinate was used for blood pressure control, and there were no cardiovascular
      side effects and no significant increase in blood pressure detected.

PMID- 14657781
TI  - Knowledge of ECT among staff of a mental health service.
AB  - Electroconvulsive therapy (ECT) is frequently projected as a controversial
      treatment to the general public. In England and Wales, user groups have reported
      an insufficient provision of information on which to base a decision regarding
      consent to ECT. In view of these findings, a study was carried out to assess the
      knowledge of ECT among mental health staff in a general hospital setting, as they
      are frequently the source of information for patients and caregivers. All staff
      in the mental health unit were invited to complete a semistructured questionnaire
      that consisted of questions about ECT including their knowledge of the laws about
      informed consent. Seventy-five staff members, representing about two thirds of
      the staff population, returned the questionnaires. Seventy of them responded that
      they knew the indications for ECT, of which the most frequently quoted were
      depression, mania, and schizophrenia. Only 24 (36.9%) staff members knew of the
      guidance with respect to informed consent and ECT. The finding in this study led
      to a revision of the local ECT training program for patients, caregivers, and
      staff. A review of the impact of the changes made will take place in the future.
      The Royal College of Psychiatrists itself has decided to implement changes by
      setting up a commission to assess and accredit various ECT units in England and
      Wales.

PMID- 14657782
TI  - Quality of life in dementia: ten years later.

PMID- 14657783
TI  - Whose quality of life is it anyway? The validity and reliability of the Quality
      of Life-Alzheimer's Disease (QoL-AD) scale.
AB  - Quality of life (QoL) is becoming an increasingly used outcome measure in both
      clinical practice and research. There are now more than 1000 scales available to
      measure QoL, and it is important that they are assessed for reliability and
      validity. This study aims to assess the reliability and validity of the Quality
      of Life-Alzheimer's Disease (QoL-AD) scale, which is dementia specific and brief
      and uses the patient's own responses. Two separate samples of people with
      dementia (sample 1, n = 60; sample 2, n = 201) were assessed. Five focus groups
      were conducted involving both people with dementia and their caregivers; the
      focus groups showed that people with dementia had higher hopes for their QoL than
      their caregivers did for them. Questionnaires about the scale were completed by
      71 health care professionals working with people with dementia. The scale was
      found to have good content validity with no additional items required and all
      items necessary. It also correlated well with the Dementia Quality of Life scale
      (0.69) and with the Euroqol-5D scale (0.54), indicating good criterion concurrent
      validity. Construct validity was also good with the principal components analysis
      showing all 13 items of the QoL-AD loaded on component 1. Interrater reliability
      was excellent with all Cohen's kappa values >0.70. Internal consistency was
      excellent with a Cronbach's alpha coefficient of 0.82. Some people with severe
      dementia and a Mini-Mental State Examination score as low as 3 were able to
      satisfactorily complete the QoL-AD. The QoL-AD has very good psychometric
      properties and can be completed with people with a wide range of severity of
      dementia.

PMID- 14657784
TI  - Health-related quality of life for caregivers of patients with Alzheimer disease.
AB  - We investigated the relationship of caregivers' health-related quality of life
      (HRQOL) to the burden of caring for patients with Alzheimer disease (AD) and
      resource utilization. Caregiver HRQOL was assessed using the SF-12 Mental and
      Physical Summary scores. Compared with a normative, age-adjusted sample, the 2477
      caregivers had lower mental and physical scores (for the latter, only those <54
      years of age). Increased caregiver mental functioning was associated with
      caregiver support and perceived quality of patient medical care, fewer hours of
      caregiving, and fewer patient behavioral symptoms. The burden of caregiving has
      substantial effects on HRQOL. Interventions that improve AD status and reduce
      caregiving hours have the potential to improve caregivers' HRQOL.

PMID- 14657785
TI  - Advance directives for health care and research: prevalence and correlates.
AB  - Patients suffering from Alzheimer disease and other types of dementia gradually
      lose their decision-making capacity. Advance directives have been widely promoted
      as a means to maintain some control over one's life in the event of decisional
      incompetence. This study used data from a recent postal survey conducted in
      Quebec, Canada to: 1) estimate the prevalence of formal and informal advance
      directives for health care and research among community-dwelling older adults
      presumed free of cognitive deficits; and 2) characterize those who have
      communicated their preferences regarding health care and research participation.
      Prevalence rates vary from 7.4% (formal advance directives for research) to 42.3%
      (informal advance directives for health care). Following multivariate logistic
      regressions, individuals who have communicated their wishes regarding future
      health care were found to be older, predominantly women, and to more often know
      someone with cognitive impairment. Those who have expressed their wishes
      regarding future research involvement were more inclined to participate in
      research. They were also more likely to have discussed or written advance
      directives for health care. The finding that only a small proportion of older
      adults have discussed future research participation with their families points to
      the need to find effective ways to promote advance directives for research in
      this population.

PMID- 14657786
TI  - Behavioral quantitation is more sensitive than cognitive testing in
      frontotemporal dementia.
AB  - OBJECTIVE: To compare behavioral and cognitive testing in the clinical diagnosis
      of frontotemporal dementia (FTD). METHODS: A clinically defined cohort of FTD (n
      = 52) is compared with 52 Alzheimer disease (AD) patients on a Frontal Behavioral
      Inventory (FBI) and cognitive tests (e.g., Mini-Mental State Examination, Mattis
      Dementia Rating Scale, Western Aphasia Battery, Wechsler Intelligence Scale,
      Wechsler Memory Scale). Fourteen patients with FTD had autopsy confirmation, and
      their tests are also compared with the rest of the FTD population. RESULTS: The
      FTD and AD groups were matched in sex, duration, and severity of dementia. The
      total scores on the FBI showed the largest difference. Mini-Mental State
      Examination and Mattis Dementia Rating Scale total scores did not discriminate
      between the two groups. Memory subscores were lower in the AD group, and
      conceptualization and language-related scores were worse in the FTD group. Milder
      and earlier affected patients, who could carry on a large battery of
      neuropsychological tests, were much better distinguished by the FBI scores on
      discriminant function analysis. In contrast to 78% by the cognitive tests, 98% of
      the FTD and AD patients were differentiated by the FBI. CONCLUSIONS: Although
      memory scores were lower in AD and language scores in the FTD population, many of
      the cognitive tests do not distinguish between FTD and AD. On the other hand, a
      behavioral inventory is a useful adjunct in the diagnosis of FTD. Postmortem
      validation was carried out in a sizeable subset of the population, showing
      similar behavioral and cognitive data.

PMID- 14657787
TI  - A Chinese translation of the EdFED-Q and assessment of equivalence.
AB  - The purpose of this study was to translate the Edinburgh Feeding Evaluation in
      Dementia Questionnaire (EdFED-Q) from the original English into a Chinese
      language version and to assess the equivalence of the English and Chinese EdFED-Q
      versions. To use a directly translated instrument without minimal explanation of
      the procedures for determining the equivalence between the original and secondary
      language instrument is questionable. Ensuring equivalence of a translated Chinese
      version of the EdFED-Q for patients with dementia is an essential prerequisite
      for identifying culturally specific expressions of feeding difficulty under
      investigation. Phase 1 consisted of experts doing the initial translation into
      Chinese and then English back-translations of the questionnaire. Six experts
      determined the equality of the Chinese and English versions, and five monolingual
      nurses provided information for the C-EdFED-Q. In phase 2, two bilingual
      gerontological nurses rated 33 residents with dementia to determine equivalence
      across time. In phase 3, three groups of bilingual nurses used the Chinese,
      English, and finally both versions simultaneously to judge a model case's feeding
      behavior on the videotape. In phase 1, the rating on the equality of the items on
      the Chinese and English versions was 0.969. In phase 2, kappa coefficients for
      all items on the C-EdFED-Q and E-EdFED-Q ranged from 0.44 to 1.00. In determining
      the consistency of the scores for the C-EdFED-Q and E-EdFED-Q between the two
      raters across time, the intraclass correlation coefficient for the absolute
      agreement was found to range from 0.85 to 0.90. In phase 3, except for items 6
      and 9, all items showed no significant difference among the three groups. Further
      studies to assess the relationship between constructs and to compare it with
      known and predicted relationships are recommended.

PMID- 14657788
TI  - Clinical features of MRI-defined subcortical vascular disease.
AB  - BACKGROUND AND PURPOSE: Vascular cognitive impairment and vascular dementia are
      now seen to extend much beyond the traditional multi-infarct dementia.A more
      homogeneous subtype is the subcortical ischemic vascular disease (SIVD). We
      applied magnetic resonance imaging (MRI) criteria based on research criteria for
      SIVD in a large cohort of patients with ischemic stroke. We compared clinical
      features of patients with SIVD and patients with other stroke type. SUBJECT AND
      METHODS: The study group comprised 337 of 486 consecutive patients aged 55 to 85
      years who 3 months after ischemic stroke completed a comprehensive
      neuropsychological test battery and MRI, including structured medical,
      neurologic, and laboratory evaluations; clinical mental status examination;
      interview of a knowledgeable informant; detailed history of risk factors; and
      evaluation of stroke type, localization, and syndrome. RESULTS: Patients with
      SIVD (n = 86) more often had a history of progressive cognitive decline (22.8%
      vs. 6.9%, P = 0.0002), walking disorder before stroke (27.9% vs. 2.0%, P = 0.02),
      and urinary difficulties (12.8% vs. 5.6%, P = 0.028) in comparison with patients
      with other stroke type (n = 251). Of the study population, 107 (31.8%) had DSM
      III dementia. The patients with SIVD more often had DSM-III dementia (40.7% vs.
      28.7%, P = 0.04), had less severe stroke as measured by Scandinavian Stroke Scale
      (56.6 vs. 55.1, P = 0.03), were more dependent in activities of daily living
      (ADL) functions as measured by FAQ scale (8.9 vs. 5.4, P = 0.001), were more
      dependent in instrumental activities of daily living (IADL) functions as measured
      by the Lawton scale (5.5 vs. 6.3, P = 0.01), and were more depressed as measured
      by the Beck Depression Inventory (11.8 vs. 8.4, P = 0.0003) poststroke than the
      patients without SIVD. The main cognitive domain that differentiated the patients
      with SIVD from those without was executive dysfunction (51.2% vs. 38.7%, P =
      0.04). According to multiple regression model, apractic-atactic gait disorder
      (odds ratio 2.82, 95% confidence interval 1.21-6.53), ADL functions (odds ratio
      1.04, 95% confidence interval 1.01-1.08), and the Beck Depression Inventory (odds
      ratio 1.05, 95% confidence interval 1.02-1.09) related to SIVD. CONCLUSIONS: The
      most significant clinical features of MRI-defined SIVD were found to be apractic
      atactic gait, impaired ADL functions, and depression.

PMID- 14657789
TI  - Donepezil plus vitamin E as a treatment in Alzheimer disease.

PMID- 14657790
TI  - Dementia update 2003.
AB  - Clinical and scientific investigations in the field of dementia expanded greatly
      in the past two decades. Medline citations that addressed Alzheimer disease (AD),
      the most common dementing disorder, rose from 78 in 1980 to 987 in 1990 and to
      1772 in 2000. Underscoring this increased body of knowledge, three practice
      parameters on dementia were published in 2001 by the Quality Standards
      Subcommittee of the American Academy of Neurology. Although some older studies
      are included for context, this review focuses on selected recent advances in
      dementia that are relevant for the practicing physician. Topics covered include:
      1) diagnosis of dementia; 2) risk factors and biomarkers; 3) mild cognitive
      impairment; 4) the scientific basis for treatment advances in AD; and 5) other
      dementing disorders.

PMID- 14657791
TI  - Molecular and cellular basis for anti-amyloid therapy in Alzheimer disease.

PMID- 14657792
TI  - [Is there a "French exception" for prevention? The example of childhood
      accidents].

PMID- 14657793
TI  - [Causes of death of COGEMA active workers, 1980-1995].
AB  - BACKGROUND: Populations exposed to risks at work show a deficit in deaths in
      comparison with the national population, the "healthy worker effect". This effect
      has been observed among former nuclear workers. The aim of our cross-sectional
      study was to evaluate the mortality in a metallurgy worker population, and to
      study the impact of the choice of the reference population on the estimation of
      the Standardized Mortality Ratio (SMR). METHODS: The studied population was the
      COGEMA Metallurgy Department workers, aged 25 years to 64, during the period 1980
      1995 in two regions of France (North--La Hague; South--Cadarache, Marcoule,
      Miramas and Pierrelatte). In order to account for geographical variability and
      the difference in mortality between the working population and the non-working
      population, we used several reference populations: national population, regional
      population, "working" national population (farmers not present in COGEMA and non
      workers excluded), and "working" regional population. RESULTS: All SMRs were
      increased when we used a "working" regional reference compared with the national
      reference population. Among men, eight pathologies presented a significant
      deficit with a national reference, whereas only two pathologies showed a deficit
      with the "working" regional reference. CONCLUSION: The use of a reference
      population close to the study population enabled us to reduce the Healthy Worker
      Effect among metallurgy workers at COGEMA plants.

PMID- 14657794
TI  - [Causes of death in a cohort of EDF-GDF employees: comparison between
      occupational medicine and official statistics data].
AB  - BACKGROUND: In an epidemiological study, medical causes of death may be obtained
      from different sources. In a study on French gas and electricity company (EDF
      GDF) workers, they were obtained from the national INSERM database. Additionally,
      the causes collected by the EDF-GDF occupational physicians were available for a
      subset of 1,330 deaths, which occurred between 1989 and 1994. The data from the
      two sources were compared with each other, in order to assess whether they were
      globally equivalent, and the potential impact of their differences on the results
      of epidemiological analyses. METHODS: Concordance rates between causes of death
      in the INSERM and EDF-GDF physicians databases were calculated according to the
      International Classification of Diseases (ICD) ninth revision codes and for
      various causes groups. Causes of death records were also examined in order to
      clarify the observed divergences. SMRs were computed in order to evaluate the
      consequences of using each database in epidemiological analyses. Finally, some
      SMRs were computed with the two sources and compared with each other. RESULTS:
      INSERM and EDF-GDF physicians causes belonged to the same causes group in 81% of
      cases, but the exact cause was different for more than half of them. The
      concordance rate was high for the deaths by AIDS and by cancer, and low for
      deaths by respiratory system and digestive system diseases. More causes of death
      were coded as "unknown" in EDF-GDF physicians data than in INSERM data. The SMRs
      varied widely depending on whether the INSERM or EDF-GDF physicians causes of
      death databases were used. CONCLUSIONS: Causes of death recorded in the INSERM
      and EDF-GDF physicians databases are very different. Therefore, using the
      national mortality rates computed by INSERM with the EDF-GDF physicians causes of
      death to calculate SMRs is not valid, and it is observed that they may be very
      different from those computed with INSERM data. In a general way, it should be
      better to use the INSERM database, which is a common source, in order to generate
      results comparable with other studies. However, this database has its own
      limitations, and it may be better, in particular situations and for internal
      analyses, to use another source if it seems to be a better one.

PMID- 14657795
TI  - [Mortality among active workers at EDG-GDF: social and occupational disparities
      and evolution].
AB  - BACKGROUND: Two studies, conducted in the eighties and the nineties, reported
      that mortality was lower in the French national electric and gas company (EDF
      GDF) the utility workers than in the general French population. The purpose of
      our study was to compare the mortality of these 140,000 utility workers to that
      of the French population of the same age for the period from 1997 to 2001.
      Secondly we aimed to assess the disparities of mortality among the workforce
      according to demographic and socioprofessional criteria. Finally, we analyzed the
      evolution of this mortality over the last twenty years. METHODS: We undertook a
      cross-sectional study using the indirect standardization method. RESULTS: Risk of
      death was lower in the utility workers than in the French population (SMR=54% for
      men, and 58% for women). These differences had increased over the last twenty
      years for each main cause of death (cancers, cardio-vascular diseases and
      accidents). The reported excess of brain cancer death risk raises etiologic
      questions. Moreover, we noticed important social disparities in the workforce,
      increasing with time. CONCLUSION: The well-known "healthy worker effect" seems to
      be particularly important in the EDF-GDF company. The workers have a high level
      of living conditions and good working conditions, although internal social
      disparities persist. Further studies in other large corporations are greatly
      needed for comparisons.

PMID- 14657796
TI  - [Quantification of the probability of milk contamination by Listeria
      monocytogenes during manufacture of hard cheese].
AB  - BACKGROUND: The present work is concerned with the probability of contamination
      by Listeria monocytogenes in the artisanal manufacture of Swiss Emmental hard
      cheese made from raw milk. The simulation model follows the evolution of the
      contaminant flora from raw milk at the farm to milk mixing, storage at the cheese
      factory and to the cheese manufacturing process. METHODS: The simulations are
      based on models of predictive microbiology, namely the exponential growth model
      of bacteria including the lag-time, a cardinal growth model and a Log-linear
      model of thermal deactivation of bacteria. RESULTS: The results of the actual
      simulation indicate that the contamination of milk at the farm is a rare event
      (P=0.0036), but the mixing of milk at the cheese factory leads to a higher
      probability of contamination of cheese milk (P=0.07). Elevated bacterial
      concentrations are mainly due to cases of mastitis involving Listeria
      monocytogenes. The decline in bacterial counts during cheese manufacture depends
      on the curing temperature (52-54 degrees C) and varies between 1.5 and 3.2 Log
      cfu/ml. Freshly manufactured Emmental-cheese made from contaminated raw milk is
      expected to have only 4.6 cfu of heat injured Listeria monocytogenes /kg cheese
      mass in the press. CONCLUSION: Depending on listeria evolution, from the press to
      the product consumption, consumer exposure has been evaluated and might result in
      1 to 10 Listeria monocytogenes per portion of cheese. The bacterial presence
      could be due to recontamination during packaging, distribution and cheese
      preparation by the consumer. Based on the presented data and estimations, it is
      concluded that the consumption of traditionally/artisanal manufactured Swiss
      Emmental hard cheese presents an extremely low, but existent risk, especially for
      people with a deficient or diminished immune system.

PMID- 14657797
TI  - [Quality of care and sexually transmitted infections algorithm acceptability in
      Burkina Faso].
AB  - BACKGROUND: To assess sexually-transmitted infections (STIs) quality of care,
      syndromic approach acceptability and applicability by patients and health workers
      in Burkina Faso. METHOD: Three approaches were used: simulated patients method to
      assess quality of STIs care, patients interview and focus discussion with health
      workers to assess syndromic approach acceptability and applicability. RESULTS:
      Sixty-two anonymous visits were made in 17 Bobo-Dioulasso primary care clinics.
      Overall, history taking were assessed in 77.4% of visits, 47% patients were
      physically examined. Women (71%) were examined more frequently than men (41%)
      (P=0.01), 42% of patients were not examined in an isolated room. Medication was
      prescribed for 87.1% of the patients but only 37.5% of the treatments were
      applied according to national recommendations. Counselling was poor concerning
      critical messages regarding risk of HIV transmission, STI prevention. Patients
      and health workers found the syndromic approach acceptable and applicable, but
      the question of sexual behaviour was considered difficult to address. CONCLUSION:
      Quality of STIs care is poor in Burkna Faso. Staff training must emphasize
      interpersonal communication and motivation, with introduction of a sexually
      transmitted infection syndrome package consisting of drugs and condoms in order
      to improve syndromic case management.

PMID- 14657798
TI  - [Missing data mechanisms of the questionnaire SF-36's items in the SU.VI.MAX
      study].
AB  - BACKGROUND: Health related quality of life is becoming of greater importance in
      the medical field. Nevertheless, methodological problems persist, and
      particularly when it comes to processing missing data on quality of life
      questionnaires. In fact, this leads to three difficulties: (i) loss of power;
      (ii) bias; (iii) choice of the most adequate method for treating missing data.
      Prevention is the best recommendation in order to avoid unanswered questions.
      Unfortunately, this does not guarantee the absence of missing data. Therefore,
      the treatment of missing data depends on: i) identification of the missing data
      mechanism and ii) choice of the most appropriate method to correct the data. The
      main objective of this article is to illustrate the identification of non
      response items as described in the SF-36 questionnaire items in the SU.VI.MAX
      study. METHODS: A logistic regression on the characteristics of the subjects was
      used to distinguish between two missing data mechanisms: missing completely at
      random (MCAR) and missing at random (MAR). Two global Chi-2 tests on MCAR
      mechanism were proposed. The missing data not at random (MNAR) mechanism was also
      analysed considering the questionnaire features. RESULTS: The percentage of non
      responses was small (1.7%), with a maximum equal to 3% for four questions of the
      General Health dimension (GH2 to GH5). Both global Chi-2 tests rejected the
      hypothesis that all SF-36 non-responses were MCAR. As to the 32 items with less
      than 2.3% of non-responses, the mechanisms were: MCAR for 29 items, MAR for 2
      items, and probably MNAR for 1 item. The logistic regression indicates that the
      factors related to non-responses were gender (female), age (> or =50 years),
      attention problem, and number of children (> or =3). The hierarchical feature of
      item PF5 (climb one flight of stairs) in relation to PF4 (climb several flights
      of stairs) would be a generator MNAR non-responses. The "I don't know" response
      modality of bloc GH2 to GH5 would also be generator of non-responses of the MNAR
      type. CONCLUSION: The identification of missing data mechanisms through
      statistical analysis and through further reflection on the questionnaire's
      features is a necessary preliminary in the treatment of non-responses.

PMID- 14657799
TI  - [Urban particulate air pollution: from epidemiology to health impact in public
      health].
AB  - Major air pollution accidents which occurred in the 1950s led to public awareness
      of the health hazards involved. Since that period, levels of air pollution have
      decreased, but several studies conducted in North America and Europe indicate
      that particulate air pollution is linked to increased cardiorespiratory morbidity
      and mortality. Despite this evidence, several questions were raised concerning
      the interpretation of the results (threshold effect, harvesting effect and
      biological plausibility). The aim of this review is to present the link between
      epidemiological findings and their use in health impact assessment. We review the
      main causal criteria applied to epidemiology in light of scientific evidence
      currently available. Some causality criteria are more important than others, but
      they all support the causal nature of the relationship between air pollution and
      health, and thus justify the feasibility of health impact assessment
      calculations. Recent studies on relative risk assessment show that even if the
      risk linked to worsening air quality is low, public health consequences are high.
      Such information must be made accessible to policy makers and the population in
      general so that, together with the public health workers, they can all contribute
      to improving air quality and health in their communities.

PMID- 14657800
TI  - [Is evidence-based medicine useful for public health?].
AB  - Evidence-based medicine is a fashionable topic although the discussions is open
      regarding whether it has any practical interest for daily medical practice or
      public health policy. One needs therefore to focus on the way evidence-based
      medicine can improve matters for physicians, but also on some serious challenges
      facing health professionals. Upon close examination, it appears that evidence
      based medicine provides us with concepts and methods likely to be useful in three
      directions: improvement of the health care decision-making process, reinforcement
      of professional accountability dedicated to the promotion of human rights,
      implementation of fair health policy regulations taking into account the
      intricate relationships between participants dealing with individual or community
      oriented interventions. When facing these challenges, evidence-based medicine
      certainly deserves further attention in the field of community and public health.

PMID- 14657801
TI  - [Development of a general medicine database].

PMID- 14657802
TI  - Efalizumab (Raptiva) for treatment of psoriasis.

PMID- 14657803
TI  - New glucose-monitoring devices.

PMID- 14657804
TI  - Safety of canadian drugs.

PMID- 14657805
TI  - Global reduction of Hib disease: what are the next steps? Proceedings of the
      meeting Scottsdale, Arizona, September 22-25, 2002.
AB  - On September 22 to 25, 2002, a group of infectious disease specialists, public
      health officials, and vaccine experts from 33 countries gathered in Scottsdale,
      Arizona, to discuss the epidemiology and control of disease caused by Haemophilus
      influenzae type b (Hib) in the era of Hib conjugate vaccines. This supplement is
      a synthesis of the major themes and key lessons identified at the meeting. The
      objectives of the conference were to review the 10-year experience with Hib
      conjugate vaccines, discuss strategies to reduce Hib disease rates to lowest
      possible levels in industrialized countries, review impediments to the
      introduction of Hib vaccine in developing countries, and discuss strategies for
      disseminating lessons learned from countries using to those not using Hib
      conjugate vaccines. Over 10 years of international experience with Hib conjugate
      vaccines has demonstrated that they are safe and effective. Routine use of Hib
      conjugate vaccine has consistently led to decreases in the incidence of invasive
      Hib disease of 90% or more across a wide range of epidemiologic situations in
      industrialized countries. In some countries, the vaccine has caused a near
      disappearance of invasive Hib disease through a combination of direct protection
      and herd immunity. Developing countries that have implemented routine vaccination
      (eg, The Gambia, Chile) have also had substantial disease reduction. In countries
      where Hib conjugate vaccine is being used, reducing Hib disease incidence to the
      lowest possible level will depend on maintaining high vaccine coverage levels,
      conducting surveillance for Hib disease, and investigating Hib disease cases. The
      optimal Hib vaccination strategy will depend on many factors, including local
      epidemiology and programmatic considerations. In countries that are not using Hib
      conjugate vaccine, information on the local burden of Hib disease will be
      essential for leaders considering vaccine introduction. Where disease burden is
      high, a multifaceted approach is urgently needed to evaluate and overcome
      barriers to vaccine introduction. In areas where Hib disease burden is not well
      characterized, additional work will be needed to understand the epidemiology of
      Hib disease and to communicate the value of Hib conjugate vaccine.

PMID- 14657806
TI  - The rationale for productivity-based physician compensation at academic health
      centers.

PMID- 14657807
TI  - Antioxidants and oxidations in bronchopulmonary dysplasia: there are no easy
      answers.

PMID- 14657808
TI  - Blood pressure and the brain.

PMID- 14657809
TI  - Corticosteroids for first-time young wheezers: current status of the controversy.

PMID- 14657810
TI  - Mirror images: is levalbuterol the fairest of them all?

PMID- 14657811
TI  - The journey to metabolic control in diabetes: many more miles to go.

PMID- 14657812
TI  - Newborn screening for cystic fibrosis: ensuring more good than harm.

PMID- 14657813
TI  - N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants:
      a randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether N-acetylcysteine (NAC) infusion during the first
      week of life reduces the risk of death or bronchopulmonary dysplasia (BPD) in
      infants with extremely low birth weight. Study design In a Nordic multicenter,
      double-blind trial, infants (n=391) weighing 500 to 999 g and on ventilator or
      nasal continuous positive airway pressure were randomized before the age of 36
      hours to receive NAC 16 to 32 mg/kg/d (n=194) or placebo (n=197) intravenously
      for 6 days. Primary end points were death or BPD, defined as supplementary oxygen
      requirement at 36 weeks' gestational age. RESULTS: There was no difference in the
      combined incidence of the primary end points death or BPD, 51% vs. 49%, between
      the NAC group and control group. Also similar was the incidence of BPD in
      survivors at 36 weeks' gestational age, 40% vs. 40%, and the mean oxygen
      requirement at the age of 28 days, 31.2% vs. 30.7%, respectively. The severity of
      BPD was similar in both groups. CONCLUSIONS: A 6-day course of intravenous N
      acetylcysteine at the dosage used does not prevent BPD or death in infants with
      extremely low birth weight.

PMID- 14657815
TI  - Elevated blood pressure and decreased cognitive function among school-age
      children and adolescents in the United States.
AB  - OBJECTIVE: To evaluate the relationship between elevated blood pressure (BP) and
      cognitive test performance in a nationally representative sample of children.
      Study design The National Health and Nutrition Examination Survey III provides
      cross-sectional data for children 6 to 16 years, including BP and cognitive test
      scores. Elevated BP was defined as systolic or diastolic BP >or=90th percentile.
      Cognitive tests were compared for children with elevated and normal BP. Linear
      regression was used to evaluate the relation between elevated BP and decreased
      test scores. RESULTS: Among the 5077 children, 3.4% had systolic BP >or=90th
      percentile and 1.6% diastolic BP >or=90th percentile. Children with elevated
      systolic BP had lower average scores compared with normotensive children for
      digit span (7.9 vs 8.7, P=.01), block design (8.6 vs 9.5, P=.03), and mathematics
      (89.6 vs 93.8, P=.01). Elevated diastolic BP was associated with lower average
      scores on block design (9.5 vs 11, P=.01). Linear regression showed that elevated
      systolic BP was independently associated with lower digit span scores (P=.032).
      CONCLUSION: Children with elevation of systolic BP are at risk for central
      nervous system end-organ damage, as manifested by decreased digit span test
      scores.

PMID- 14657816
TI  - Oral prednisolone in the acute management of children age 6 to 35 months with
      viral respiratory infection-induced lower airway disease: a randomized, placebo
      controlled trial.
AB  - OBJECTIVE: To investigate the efficacy of oral prednisolone in virally induced
      respiratory distress. Study design Randomized, double-blind, placebo-controlled
      trial involving 230 children age 6 to 35 months in the emergency department. Each
      patient received either oral prednisolone (2 mg/kg/d) or placebo for 3 days.
      RESULTS: The hospitalization rates were similar between the two groups. For
      admitted children (n=123), the median length of stay was 1 day shorter in the
      prednisolone group (2 vs 3 days, P=.060). The proportion of children requiring
      >or=3 days of hospitalization was 47.5% in the prednisolone group and 67.7% in
      the placebo group (P=.023). There was less need for additional asthma medication
      (18.0% vs 37.1%, P=.018) in the prednisolone group. The median duration of
      symptoms of respiratory distress was 1 day in the prednisolone group versus 2
      days in the placebo group both among the hospitalized (P<.001) and
      nonhospitalized children (P=.006). CONCLUSION: A 3-day course of oral
      prednisolone effectively reduced disease severity, length of hospital stay, and
      the duration of symptoms among children 6 to 35 months old with virally induced
      respiratory distress.

PMID- 14657817
TI  - Comparison of racemic albuterol and levalbuterol for treatment of acute asthma.
AB  - OBJECTIVE: To determine whether levalbuterol resulted in fewer hospital
      admissions than racemic albuterol when used for treatment of acute asthma. Study
      design A randomized, double-blind, controlled trial was conducted in the
      emergency department (ED) and inpatient asthma care unit of an urban tertiary
      children's hospital. Children age 1 to 18 years (n=482) provided a total of 547
      enrollments. Patients received a nebulized solution of either 2.5 mg racemic
      albuterol or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients
      admitted to the asthma care unit were treated in a standardized fashion by using
      the same blinded drug assigned in the ED. Hospitalization rate was the primary
      outcome. RESULTS: Hospitalization rate was significantly lower in the
      levalbuterol group (36%) than in the racemic albuterol group (45 %, P=.02). The
      adjusted relative risk of admission in the racemic group compared with the
      levalbuterol group was 1.25 (95% confidence interval, 1.01-1.57). Hospital length
      of stay was not significantly shorter in the levalbuterol group (levalbuterol,
      44.9 hours; racemic albuterol, 50.3 hours; P=.63). No significant adverse events
      occurred in either group. CONCLUSIONS: Substituting levalbuterol for racemic
      albuterol in the ED management of acute asthma significantly reduced the number
      of hospitalizations.

PMID- 14657818
TI  - Reduced hypoglycemic episodes and improved glycemic control in children with type
      1 diabetes using insulin glargine and neutral protamine Hagedorn insulin.
AB  - OBJECTIVE: The purpose of this study was to evaluate the use of a new long-acting
      basal insulin, insulin glargine (IG), in children with type 1 diabetes. Study
      design Data from 114 subjects, age 2 to 18 years (mean, 12.2 years; 54 boys, 60
      girls), were collected for 9 months before and 9 months after IG treatment.
      During IG therapy, all subjects received morning neutral protamine Hagedorn
      insulin (given with insulin lispro; Humalog) to provide daytime insulin coverage.
      The numbers of nonsevere and severe hypoglycemic events, hemoglobin A1c values,
      body weight, and daily insulin dose were recorded at each clinic visit. RESULTS:
      The mean (+/-1 SEM) frequency of nonsevere hypoglycemic events per week decreased
      from 2.0+/-0.1 to 1.3+/-0.1 (P<.001). Severe hypoglycemic episodes were reduced
      from a total of 22 in the 9 months before IG to nine in the 9 months after IG.
      Severe nocturnal events were similarly reduced from 14 to four episodes. The mean
      (+/-1 SEM) hemoglobin A1c levels were 9.6+/-0.1% (baseline), 9.4+/-0.1% at 3
      months (P=.18), 9.3+/-0.1% at 6 months (P=.03), and 9.3+/-0.1% at 9 months
      (P=.01). CONCLUSION: Insulin glargine therapy can reduce hypoglycemic episodes in
      children and adolescents with suboptimal glucose control without jeopardizing
      glycemic control.

PMID- 14657819
TI  - Benefit and risk of heparin for maintaining peripheral venous catheters in
      neonates: a placebo-controlled trial.
AB  - OBJECTIVES: Heparin addition to infusion fluids is used to prolong catheter
      patency in newborns. Heparin may also induce adverse effects such as bleeding
      complications and immune-mediated heparin-induced thrombocytopenia (HIT). One
      objective was peripheral venous catheter patency with heparinization of
      continuous infusions (0.5 IU/mL). Secondary objectives were incidences of
      bleeding, clinically manifest HIT, HIT antibodies, and catheter-related
      complications. STUDY DESIGN: Inclusion criteria were anticipated need for
      intravenous peripheral infusion (>or=5 days for HIT-related endpoints) and
      postnatal age <28 days at study entry. Exclusion criteria were bodyweight <1000
      g, congenital malformation, need for therapeutic anticoagulation or mechanical
      ventilation, and severe bleeding. HIT antibodies were assessed by enzyme-linked
      immunosorbent assay. RESULTS: A total of 145 infants received heparin, and 151
      infants received saline. Patient characteristics, number of additional drugs,
      duration of treatment, and location and size of catheters did not differ. Patency
      of catheters was 7.4 hours longer in the heparin group (33.8 hours vs 26.4 hours,
      P<.0001), but the total numbers of catheters did not differ (565 vs 692, P=.3).
      No infant developed HIT antibodies. Incidences of bleeding complications and
      thrombocytopenia were comparable between groups. CONCLUSIONS: Balancing the
      benefits against the risks of heparin addition and the rare complication of HIT,
      we will not use 0.5 IU/mL heparin addition to parenteral fluids.

PMID- 14657821
TI  - Angiotensin-converting enzyme DD genotype is associated with worse perinatal
      cardiorespiratory adaptation in preterm infants.
AB  - OBJECTIVES: The angiotensin-converting enzyme (ACE) deletion (D) variant is
      associated with greater ACE activity and perhaps with deleterious
      cardiorespiratory pathophysiological responses. We determined whether the early
      health status of the preterm infant was adversely influenced by homozygosity for
      the D allele (DD genotype) compared with ID or II genotype. Study design
      Angiotensin-converting enzyme genotype was determined in a cohort of 148 preterm
      infants born in Bristol, United Kingdom (median gestational age, 31 weeks; range,
      28-32). Intensive care data were prospectively obtained. Primary analysis was by
      Mann-Whitney U and chi(2) tests. RESULTS: Higher oxygen, circulatory support
      requirements, and base deficit in the first 12 hours after birth were found in
      infants with DD genotype (minimum inspired oxygen concentration in first 12
      hours, median [interquartile range], DD 0.26 [0.21-0.40], ID/II 0.21 [0.21-0.30],
      P=.028; blood pressure support in first 12 hours, DD 12 [30%], ID/II 15 [14%],
      P=.039; worse base deficit in first 12 hours, DD 4.8 [7.7 to 0], ID/II 0 [5.3 to
      0], P=.020). CONCLUSIONS: Angiotensin-converting enzyme polymorphism has a role
      in the development of preterm cardiorespiratory disease. The DD genotype,
      encoding higher angiotensin-converting enzyme activity, may adversely influence
      the early health status of preterm infants.

PMID- 14657822
TI  - Energy expenditure in human milk- versus formula-fed preterm infants.
AB  - OBJECTIVE: We compared energy expenditure (EE) of preterm infants fed their
      mother's milk versus preterm infant formula. Study design A prospective,
      randomized crossover study of 13 healthy, appropriate weight for gestational age,
      gavage-fed, preterm infants. Before the study and according to our feeding
      protocol, infants uniformly received alternate feeds of human milk and formula.
      Each infant was randomly assigned to 24 hours of formula feeding followed by 24
      hours of breast milk or the reverse. Infants were studied asleep, at the end of
      each 24-hour period. EE was measured by indirect calorimetry 1 hour before
      feeding, 20 minutes during feeding, and 1 hour after feeding in a servo
      controlled convective incubator. Energy content of human milk was analyzed by
      bomb calorimetry. RESULTS: EE was significantly lower in breast milk-fed infants
      during prefeeding (52+/-6 vs 57+/-10 kcal/kg per 24 hours) (P<.05), per feeding
      (55+/-6 vs 60+/-10 kcal/kg per 24 hours) (P<.05), and at the postfeeding
      measurement (60+/-7 vs 65+/-7 kcal/kg per 24 hours) (P=.059). After correction of
      the results for the actual measured energy intake, all statistical differences
      reached the <.05 level. CONCLUSIONS: Preterm infants have lower EE when they are
      fed breast milk than when they are fed preterm infant formula.

PMID- 14657823
TI  - Human milk is a source of lactic acid bacteria for the infant gut.
AB  - OBJECTIVES: To investigate whether human breast milk contains potentially
      probiotic lactic acid bacteria, and therefore, whether it can be considered a
      synbiotic food. Study design Lactic acid bacteria were isolated from milk,
      mammary areola, and breast skin of eight healthy mothers and oral swabs and feces
      of their respective breast-fed infants. Some isolates (178 from each mother and
      newborn pair) were randomly selected and submitted to randomly amplified
      polymorphic DNA (RAPD) polymerase chain reaction analysis, and those that
      displayed identical RAPD patterns were identified by 16S rDNA sequencing.
      RESULTS: Within each mother and newborn pair, some rod-shaped lactic acid
      bacteria isolated from mammary areola, breast milk, and infant oral swabs and
      feces displayed identical RAPD profiles. All of them, independently from the
      mother and child pair, were identified as Lactobacillus gasseri. Similarly, among
      coccoid lactic acid bacteria from these different sources, some shared an
      identical RAPD pattern and were identified as Enterococcus faecium. In contrast,
      none of the lactic acid bacteria isolated from breast skin shared RAPD profiles
      with lactic acid bacteria of the other sources. CONCLUSIONS: Breast-feeding can
      be a significant source of lactic acid bacteria to the infant gut. Lactic acid
      bacteria present in milk may have an endogenous origin and may not be the result
      of contamination from the surrounding breast skin.

PMID- 14657824
TI  - Thyroid abnormalities by ultrasonography in neonates with congenital
      hypothyroidism.
AB  - OBJECTIVES: To investigate the usefulness of thyroid ultrasonography for neonates
      with congenital hypothyroidism. Study design Patients (n=66) were evaluated by
      ultrasonography at age 15.2+/-12 days. RESULTS: Thyroid scanning was more
      sensitive for the identification of ectopic tissue as ultrasonography showed
      ectopic thyroid tissue in only 9 of 42 cases. In cases for which no iodine uptake
      was demonstrated by thyroid scanning (n=12), ultrasonography showed normally
      located thyroid tissue in 2 patients. Therefore, on the basis of both thyroid
      scanning and ultrasonography, 10 cases were classified as athyreosis, and 14
      cases were classified as showing normal location of the thyroid gland. Among the
      latter 14 cases, 5 showed a developmental abnormality. Ultrasonography also
      revealed additional phenotypic abnormalities in patients with thyroid dysgenesis,
      with cysts (n=6) and thymus tissue (n=4) within the empty thyroid area, which are
      novel observations in these patients. CONCLUSIONS: Ultrasonography may reveal
      additional findings with regard to those obtained by scintigraphy such as
      information regarding the anatomy of the thyroid gland, presence of cysts, and
      presence of additional thymic tissue within the empty thyroid area.

PMID- 14657825
TI  - Endogenous fecal losses of calcium compromise calcium balance in pancreatic
      insufficient girls with cystic fibrosis.
AB  - OBJECTIVE: Bone mineral density is compromised in individuals with cystic
      fibrosis (CF); calcium is the major bone mineral. This study examined the impact
      of endogenous fecal calcium (V(endo)) losses on calcium balance in girls with CF.
      Study design V(endo) was measured in 12 girls with CF (aged 7-18 years): 7
      younger, premenarcheal girls with compromised nutritional status; and 5 older,
      postmenarcheal girls with adequate nutritional status. V(endo) was measured as
      the amount of intravenously administered (42)Ca, a calcium stable isotope, in
      stool relative to urine over 6 days. V(endo) was compared between pre- and
      postmenarcheal girls by Student's t test. Actual calcium balance [absorbed
      calcium-(urinary calcium (V(u))+V(endo))] was compared with estimated balance
      (assuming V(endo)=1.6 mg/kg/day calcium) by paired t test. RESULTS: V(endo) was
      99.3+/-42.3 mg/day. By body weight, V(endo) was highest among premenarcheal girls
      (3.37+/-1.09 mg/kg/day), resulting in excess losses (>1.6 mg/kg/day) of 55.0+/
      45.7 mg/day. Over 1 year, this represents 20.1+/-16.7 g of unattained bone
      calcium or 6.7+/-4.2% of the bone calcium content of these girls. CONCLUSIONS:
      V(endo) is a significant source of calcium loss in individuals with CF and may
      limit calcium availability for bone mineral deposition.

PMID- 14657826
TI  - Relation between pancreatic lipase activity and gastric emptying rate in children
      with cystic fibrosis.
AB  - OBJECTIVE: To determine whether abnormal gastric emptying is responsible for the
      inability of pancreatic enzyme replacement therapy (PERT) to normalize fat
      digestion in patients with cystic fibrosis (CF) who are pancreatic-insufficient.
      Study design Gastric emptying of a solid meal and pancreatic lipase function were
      assessed in 10 children with CF and 12 healthy control subjects with noninvasive
      breath tests using (13)C-octanoic acid and (13)C-mixed triglyceride,
      respectively. Lipase function was assessed in the subjects with CF with and
      without PERT. RESULTS: Without PERT, the lipase activity for the patients was
      less than that for the control subjects (P<.001); however, with PERT, 40% of the
      patients had a normalized lipase function. There were no differences between the
      mean gastric emptying rates of the patients with CF and the control subjects
      (P>.05), but there was a negative correlation between gastric half emptying time
      and percentage improvement in (13)C-mixed triglyceride results of the patients
      with CF with pancreatic enzymes compared with placebo (P<.05), with patients with
      slow gastric emptying having less improvement with PERT. CONCLUSIONS: The success
      of PERT in improving pancreatic lipase activity is reduced in patients with slow
      gastric emptying, which could explain the variations in improvement of fat
      digestion with enzyme supplementation.

PMID- 14657827
TI  - Brain imaging and prophylactic therapy in children with migraine: recommendations
      versus reality.
AB  - OBJECTIVES: To determine the concordance between referring physician behavior and
      published criteria for performance of imaging studies and institution of
      prophylactic therapy, respectively, in children referred to an academic
      children's hospital headache clinic. Study design A retrospective review of the
      records of 106 consecutive patients referred to an academic children's hospital
      headache clinic. RESULTS: Approximately half of patients referred to the clinic
      had already had head computed tomography or magnetic resonance imaging ordered by
      the referring doctor and performed before their clinic appointment. However,
      using published criteria, only 10% of patients seen in the clinic would have
      required an imaging procedure before institution of therapy. The referring
      physician had initiated treatment with daily prophylactic medications for
      headache in more than 30% of patients before their clinic appointments, of whom
      89% were on appropriate medications at age-appropriate and weight-appropriate
      doses. Half of these children exhibited a positive response to this medication
      before being seen by the consulting neurologist. However, more than 60% of the
      children actually met the criteria for recommending prophylactic therapy.
      CONCLUSIONS: Imaging is more frequently obtained and prophylactic therapy less
      frequently implemented by the referring physician than would be indicated by
      published recommendations.

PMID- 14657828
TI  - Prenatal exposure to polychlorinated biphenyls and attention at school age.
AB  - OBJECTIVE: To examine the relation of prenatal polychlorinated biphenyl (PCB)
      exposure to child performance on neuropsychological tests of attention and
      information processing. Study design In this prospective, longitudinal study,
      assessment of prenatal PCB exposure was based on umbilical cord serum and
      maternal serum and milk concentrations. The children were tested in their homes
      at age 11 years. Multiple regression was used to examine the relation of this
      exposure to performance on 15 neuropsychological tests after controlling for a
      broad range of potential confounding variables. RESULTS: Adverse effects were
      seen primarily in children who had not been breast fed. Among these children,
      prenatal PCB exposure was associated with greater impulsivity, poorer
      concentration, and poorer verbal, pictorial, and auditory working memory. There
      was no evidence of visual-spatial deficit or increased hyperactivity.
      CONCLUSIONS: These findings are consistent with earlier reports of greater
      vulnerability to prenatal PCB exposure in children who were not breast fed. It is
      not clear whether the protection offered by breast-feeding is caused by nutrients
      in breast milk or better quality of intellectual stimulation often provided by
      breast-feeding mothers.

PMID- 14657829
TI  - Effects of iron therapy on infant blood lead levels.
AB  - OBJECTIVES: To determine the effects of iron therapy on blood lead levels in
      infants with mildly elevated lead levels and varied iron status. METHODS: Infants
      from a community-derived sample in Costa Rica were categorized into five groups.
      Group 1 had iron-deficiency anemia with hemoglobin levels <or=105 g/L. Infants in
      group 2 were iron-deficient with intermediate hemoglobin levels (between 106-119
      g/L). These groups were treated with intramuscular iron or 3 months of oral iron.
      Group 3 (nonanemic iron-deficient) and group 4 (nonanemic iron-depleted) were
      treated with 3 months of oral iron. Group 5 (iron-sufficient) received oral
      placebo. RESULTS: After 3 months of oral iron therapy, nonanemic iron-depleted
      infants had the greatest decrease in lead levels, followed by nonanemic iron
      deficient infants and iron-deficient infants with hemoglobin levels <120 g/L.
      Lead levels increased among iron-deficient infants with hemoglobin levels <120
      g/L who received intramuscular iron and iron-sufficient nonanemic infants who
      received placebo. CONCLUSIONS: Changes in lead levels corresponded closely to
      changes in iron status and were plausible in terms of absorption mechanisms for
      lead and iron. Correcting and/or preventing iron deficiency appear to be rapid
      and effective means of improving infant lead levels, even in nonanemic infants.

PMID- 14657831
TI  - Benefits of continuous subcutaneous insulin infusion in children with type 1
      diabetes.
AB  - OBJECTIVE: To examine the effect of continuous subcutaneous insulin infusion
      (CSII) therapy on parameters affecting long-term outcome in type 1 diabetes.
      Study design Height, weight, body mass index, insulin dose, glycosylated
      hemoglobin (HbA(1C)), and blood glucose data from home meter downloads were
      collected prospectively for analysis in 51 children (age, 10.7+/-3.1 years,
      mean+/-SD) throughout the 12 months before and after introducing CSII. RESULTS:
      Before pump initiation, HbA(1C) was relatively stable, but it fell to 7.7+/-0.2%
      (P<.001) within 3 months of CSII and remained decreased (7.9+/-0.1%) at 12 months
      (P<.01). In contrast, weight standard deviation score increased before CSII (from
      0.50+/-0.13 to 0.60+/-0.13, P<.05), but remained unchanged (0.61+/-0.11) in the
      year thereafter. Although severe hypoglycemia (<50 mg/dL) was reduced in the
      entire cohort, HbA(1C) improved primarily in young children and teenagers.
      Comparison of glycemic responders (HbA(1C) <7.5, or a decrease >1% on CSII, n=23)
      with nonresponders demonstrated no differences with respect to gender,
      socioeconomic status, weight standard deviation score, body mass index, initial
      HbA(1C), frequency of hypoglycemia, or number of education visits before CSII.
      CONCLUSION: Continuous subcutaneous insulin infusion is effective in lowering
      HbA(1C) and the occurrence of severe nocturnal hypoglycemia without excessive
      weight gain in most children with type 1 diabetes. HbA(1C) response to CSII is
      poorer in preadolescents than in young children or teenagers.

PMID- 14657832
TI  - Complex regional pain syndrome after hepatitis B vaccine.
AB  - Complex regional pain syndrome, characterized by pain, autonomic dysfunction, and
      decreased range of motion, developed after hepatitis B vaccination in four grade
      6 children since the introduction of the vaccination program in British Columbia
      in 1992. The reaction may result from injection trauma or may be secondary to a
      vaccine constituent.

PMID- 14657833
TI  - Association between folic acid food fortification and congenital orofacial
      clefts.
AB  - By January 1998, most of Canada's cereal grain products were being fortified with
      folic acid. Among 336963 women who underwent antenatal maternal serum screening,
      the prevalence of orofacial clefts did not change from before (1.15 per 1000) to
      after (1.21 per 1000) food fortification (prevalence ratio, 1.06; 95% confidence
      interval, 0.86-1.30).

PMID- 14657834
TI  - Desmopressin (DDAVP)-induced pseudotumor cerebri.

PMID- 14657835
TI  - The case of the crooked cry.

PMID- 14657836
TI  - Intestinal metabolism of bilirubin in the pathogenesis of neonatal jaundice.

PMID- 14657838
TI  - Sweetened drinks and nutrition.

PMID- 14657840
TI  - Chronic heart failure-related myopathy and exercise training: a developing
      therapy for heart failure symptoms.

PMID- 14657841
TI  - Preface to atopic dermatitis intervention to control the atopic march.

PMID- 14657842
TI  - Atopic dermatitis and the atopic march.
AB  - Atopic dermatitis (AD), one of the most common skin disorders seen in infants and
      children, usually has its onset during the first 6 months of life. The prevalence
      of AD is similar in the United States, Europe, and Japan and is increasing,
      similar to that of other atopic disorders, particularly asthma. AD has been
      classified into 3 sequential phases: infantile, childhood, and adult, each with
      characteristic physical findings. AD has a tremendously negative effect on the
      quality of life of patients as well as family, most commonly disturbing sleep.
      The condition also creates a great financial burden for both the family and
      society. The cutaneous manifestations of atopy often represent the beginning of
      the atopic march. On the basis of several longitudinal studies, approximately
      half of AD patients will develop asthma, particularly with severe AD, and two
      thirds will develop allergic rhinitis. Epicutaneous sensitization has been
      thought to be responsible, with subsequent migration of sensitized T cells into
      the nose and airways, causing upper and lower airway disease. Animal models and
      human observation concur with this theory. Preliminary prevention studies with
      oral antihistamines provide evidence that early intervention might slow the
      atopic march.

PMID- 14657843
TI  - Immune mechanisms leading to atopic dermatitis.
AB  - The incidence of atopic dermatitis is increasing, and this poses a major burden
      on health care costs. A precise understanding of the genetic and immunologic
      mechanisms is crucial for development of effective treatment strategies for
      atopic dermatitis. Various studies indicate that it has a multifactorial cause,
      with activation of complex immunologic and inflammatory pathways. The current
      review will examine recent advances that have been made in our understanding of
      the genetic and pathophysiologic prerequisites that form the basis of this common
      recalcitrant skin disorder.

PMID- 14657844
TI  - Current management of atopic dermatitis and interruption of the atopic march.
AB  - Treatment of atopic dermatitis requires a comprehensive approach that includes
      evaluation of potential triggers and education of the patient and family
      regarding proper avoidance measures. Hydration of the skin and maintenance of an
      intact skin barrier remain integral to proper management. Although topical
      corticosteroids have been a mainstay of anti-inflammatory therapy, the newer
      topical calcineurin inhibitors offer advantages for treatment of this chronic,
      relapsing disease. Studies aimed at defining optimal combination therapy and
      early intervention might change the treatment paradigm for atopic dermatitis.

PMID- 14657851
TI  - Allergic rhinitis: systemic inflammation and implications for management.
AB  - Allergic rhinitis triggers a systemic increase of inflammation. Within minutes of
      allergen exposure, immune cells release histamine, proteases, cysteinyl
      leukotrienes, prostaglandins, and cytokines. Some produce the early symptoms,
      while others augment the production, systemic circulation, and subsequent
      infiltration of the nasal mucosa with inflammatory cells that sustain the
      symptoms. Systemic circulation of inflammatory cells permits their infiltration
      into other tissues where chemoattractant and adhesion molecules already exist.
      Consequently, allergic rhinitis is linked to comorbid conditions: asthma, chronic
      hyperplastic eosinophilic sinusitis, nasal polyposis, and serous otitis media.
      Effective therapy should be directed at underlying inflammation and its systemic
      manifestations. It should improve the rhinitis and the comorbid conditions.
      Antihistamines relieve early symptoms by blocking basophil- and mast cell
      generated histamine, but they do not significantly influence the pro-inflammatory
      loop. They are often little better than placebo. Oral corticosteroids provide the
      systemic anti-inflammatory efficacy, but their toxicity precludes such an
      approach. Intranasal corticosteroids effectively target the local inflammatory
      processes of rhinitis, reducing local inflammatory cells within the nares, but
      they do not directly access tissues involved in the comorbid conditions.
      Leukotriene modifiers have both systemic anti-inflammatory effects and an
      acceptable safety profile.

PMID- 14657853
TI  - IL-21: a novel IL-2-family lymphokine that modulates B, T, and natural killer
      cell responses.
AB  - IL-21 is a recently described type I cytokine produced by activated CD4(+) T
      cells that profoundly affects the growth, survival, and functional activation of
      B, T, and natural killer lymphocytes in concert with other cytokines or
      activating stimuli. Structurally, IL-21 is predicted to display a 4-helix-bundle
      type fold with significant homology to IL-2, IL-4, and IL-15 and mediates its
      biologic effects through a novel type I cytokine receptor, IL-21R, in conjunction
      with the common cytokine receptor gamma chain (gammac) of the IL-2, IL-4, IL-7,
      IL-9, and IL-15 receptors. As a new member of the gammac-dependent cytokine
      family, there is significant interest in IL-21, in part because of its potential
      to provide new insights into the immunologic phenotype caused by gammac
      deficiency. IL-21R knockout mice have been generated that have normal lymphoid
      cell development yet exhibit impaired production of the immunoglobulin IgG(1) and
      increased IgE responses after immunization. As expected for cytokines that use
      gammac, recent studies indicate that IL-21 induces Janus kinase 1 (JAK1) and JAK3
      activation to initiate signal transduction, but unlike these other gammac
      dependent cytokines, which predominantly activate signal transducer and activator
      of transcription 5 (STAT5), IL-21 preferentially activates STAT1 and STAT3. IL-21
      potently enhances primary antigen responses and the effector functions of T and
      natural killer cells and stimulates IFN-gamma production alone or in concert with
      other cytokines. Thus, on the basis of primary structure, receptor composition,
      and biologic activities, IL-21 is a new IL-2-family cytokine that participates in
      both innate and adaptive immunity and might be important for the development of a
      T(H)1 immune response.

PMID- 14657855
TI  - Practical implications of studies in occupational rhinoconjunctivitis.

PMID- 14657857
TI  - Expression profiling: opportunities and pitfalls and impact on the study and
      management of allergic diseases.

PMID- 14657858
TI  - Nasal mucosal gene expression in patients with allergic rhinitis with and without
      nasal polyps.
AB  - BACKGROUND: Nasal polyps are a common problem that is difficult to diagnose and
      treat, in part because the cause of nasal polyposis is unknown. Although
      information on the pathogenesis of polyposis is lacking, there are reports
      suggesting that a genetic predisposition underlies this disorder. OBJECTIVE: We
      sought to better understand the basis of nasal polyposis associated with allergic
      rhinitis. We hypothesize that the expression of unique genes is associated with
      the nasal polyposis phenotype. METHODS: We examined 12000 human genes transcribed
      in the nasal mucosa of patients with allergic rhinitis with and without nasal
      polyps. Biopsy specimens of the mucosa of patients with and without polyps were
      obtained after the patients refrained from the use of topical or systemic steroid
      therapy for 2 weeks. RESULTS: Thirty-four genes were differentially expressed
      between the patient groups, including those for inflammatory molecules and
      putative growth factors. The greatest differential expression identified by the
      array analysis was for a group of genes associated with neoplasia, including
      mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared
      with control patients with rhinitis alone. Quantitative RT-PCR confirmed this
      differential expression and documented that the number of mammaglobin mRNA copies
      is actually 64-fold greater in tissues of patients with polyps versus control
      patients. The specificity of mammaglobin protein expression was evaluated by
      means of immunohistochemistry, which showed specific staining in nasal polyp
      mucosal goblet cells only in patients with polyps. CONCLUSION: These data suggest
      that nasal polyposis involves deregulated cell growth, using gene activation in
      some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown
      function associated with breast neoplasia, might be related to polyp growth.

PMID- 14657859
TI  - Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and
      poorly inhibited by glucocorticoids.
AB  - BACKGROUND: Matrix metalloproteinase (MMP)-9 levels are increased in
      bronchoalveolar lavage (BAL) fluid from patients with severe asthma on high doses
      of glucocorticoids (GCs). OBJECTIVE: We sought to identify neutrophils as the
      source of increased BAL fluid MMP-9 in severe asthma and to evaluate the effects
      of GCs on this MMP-9. METHODS: MMP-9 protein, activity, and mRNA were measured in
      BAL fluid and cells at baseline, and after in vitro GCs in patients with severe
      asthma and controls using enzyme immunoassays, zymography, Western blotting, and
      real-time PCR. RESULTS: The high molecular weight (HMW) form of MMP-9 was
      significantly increased in severe asthma (P =.02). Western blotting confirmed a
      heterodimer of MMP-9 and neutrophil gelatinase-associated lipocalin. The HMW MMP
      9 correlated with BAL neutrophils (r =.65, P <.0001). BAL cell supernatant MMP-9
      protein levels also tended to be higher in patients with severe asthma (overall,
      P =.09), whereas the HMW activity form was increased (P =.03). MMP-9 protein (and
      HMW activity) correlated with neutrophils in the cell pellet (r =.75, P <.0001).
      In contrast to protein and activity, BAL cell mRNA levels were marginally lower
      in patients with severe asthma than in control subjects (overall, P =.06).
      Although GCs decreased BAL cell MMP-9 protein and mRNA in vitro, the effect was
      significantly smaller in severe asthma (P <.01 for both). GCs decreased the pro
      MMP-9 activity in patients with severe asthma and normal control subjects, while
      having no effects on the HMW form (P =.22). Peripheral blood neutrophil MMP-9
      protein was not affected by GCs. CONCLUSIONS: BAL neutrophils contribute to BAL
      fluid MMP-9 protein and activity and are poorly inhibited by GCs.

PMID- 14657861
TI  - Allergen-induced cytokine production, atopic disease, IgE, and wheeze in
      children.
AB  - BACKGROUND: The early childhood allergen-induced immune responses associated with
      atopic disease and IgE production in early life are not well understood.
      OBJECTIVE: We assessed the relationship of allergen-induced cytokine production
      by PBMCs to both atopic disease and to IgE increase in a cohort of children with
      a parental history of allergy or asthma (n = 112) at a median of 2 years of age.
      We examined cockroach (Bla g 1)-induced, house dust mite (Der f 1)-induced, and
      cat (Fel d 1)-induced cytokine secretion, including secretion of IFN-gamma, IL
      13, IL-10, and TNF-alpha. We investigated whether distinct cytokine patterns
      associated with atopic disease can be detected in immune responses of children.
      METHODS: PBMCs were isolated, and allergen-induced cytokine secretion was
      analyzed by means of ELISA. Atopic disease was defined as physician- or nurse
      diagnosed eczema or hay fever. Increased IgE was defined as an IgE level of
      greater than 35 U/mL to dust mite, cockroach, cat, and egg white or a total IgE
      level of 60 U/mL or greater. RESULTS: Compared with children without atopic
      disease, children with atopic disease had lower Der f 1 (P =.005) and Bla g 2 (P
      =.03) allergen-induced IFN-gamma levels. Compared with children without increased
      IgE (n = 95), those with increased IgE (n = 16) had higher Der f 1-induced (P
      =.006) and Fel d 1-induced (P =.005) IL-13 levels and lower Bla g 2-induced (P
      =.03) IFN-gamma levels. Compared with children with neither atopic disease nor
      repeated wheeze, children with both atopic disease and repeated wheeze had lower
      levels of allergen-induced IFN-gamma (P =.01 for Der f 1 and P =.02 for Bla g 2)
      cytokine secretion. CONCLUSION: In young children at risk for asthma or allergy,
      decreased allergen-induced IFN-gamma secretion is associated with atopic disease
      and, in some cases, with increased IgE levels. Increased allergen-induced IL-13
      secretion is most strongly associated with early life increase of IgE.

PMID- 14657862
TI  - Respiratory syncytial virus-induced airway hyperresponsiveness is independent of
      IL-13 compared with that induced by allergen.
AB  - BACKGROUND: IL-13 is a central mediator of allergen-induced airway
      hyperresponsiveness (AHR), but its role in respiratory syncytial virus (RSV)
      induced AHR is not defined. The combination of allergen exposure and RSV
      infection is known to increase AHR and lung inflammation, but whether IL-13
      regulates this increase is similarly not known. OBJECTIVE: Our objective was to
      determine the role of RSV infection and IL-13 on airway responsiveness and lung
      inflammation on sensitized and challenged mice. METHODS: Using a murine model of
      RSV infection and allergen exposure, we examined the role of IL-13 in the
      development of AHR and lung inflammation in IL-13 knockout mice, as well as using
      a potent IL-13 inhibitor (IL-13i). Mice were sensitized and challenged to
      allergen, and 6 days after the last challenge, they were infected with RSV. IL-13
      was inhibited using an IL-13 receptor alpha(2)-human IgG fusion protein. AHR to
      inhaled methacholine was measured 6 days after infection, as was bronchoalveolar
      lavage fluid and lung inflammatory and cytokine responses. RESULTS: RSV-induced
      AHR was unaffected by the IL-13i, despite prevention of goblet cell hyperplasia.
      Similar results were seen in IL-13-deficient mice. In sensitized and challenged
      mice, RSV infection significantly increased AHR, and after IL-13i treatment, AHR
      was significantly reduced, but to the levels seen in RSV-infected mice alone.
      CONCLUSIONS: These results indicate that despite some similarities, the
      mechanisms leading to AHR induced by RSV are different from those that follow
      allergen sensitization and challenge. Because IL-13 inhibition is effective in
      preventing the increases in AHR and mucus production in sensitized and challenged
      mice infected with RSV, IL-13i could play an important role in preventing the
      consequences of viral infection in patients with allergic asthma.

PMID- 14657863
TI  - Asthma variability in patients previously treated with beta2-agonists alone.
AB  - BACKGROUND: According to national asthma guidelines, asthma severity can be
      classified as intermittent, mild, moderate, or severe on the basis of lung
      function, symptoms, nighttime awakenings, and exacerbations. Although it is
      widely believed that patients might not remain consistently in any given severity
      category over time, few studies have examined this directly. OBJECTIVE: We sought
      to assess the variability in disease severity-control among patients with
      persistent asthma who have not yet received an asthma maintenance treatment.
      METHODS: We performed an analysis of asthma severity-control over time in placebo
      treated patients (n = 85) from 2 randomized, double-blind, 12-week clinical
      trials in patients with asthma previously receiving beta(2)-agonists alone.
      Asthma severity-control was assessed on the basis of morning percent predicted
      peak expiratory flow, albuterol use, and symptoms. RESULTS: At baseline, all
      patients met the criteria for moderate or severe persistent asthma (mean FEV(1)
      of 64% of predicted value or albuterol use and symptoms on 4.7 and 6.0 days per
      week, respectively). The mean percentage of treatment weeks that patients met all
      criteria for intermittent, mild, moderate, and severe asthma were 9%, 14%, 71%,
      and 6%, respectively. On the basis of morning peak expiratory flow, patients were
      classified as having intermittent-mild, moderate, or severe disease on 52%, 41%,
      and 7% of days, respectively. With regard to days per week with albuterol use or
      asthma symptoms, patients spent 59% and 45% of weeks, respectively, in the
      intermittent and mild categories. CONCLUSION: Asthma control cannot be adequately
      assessed in many patients by using discrete point-in-time assessments of lung
      function, short-acting beta-agonist use, or asthma symptoms. This might lead to
      underestimation of disease severity and contribute to inadequate therapy and,
      ultimately, asthma morbidity.

PMID- 14657864
TI  - Association between beta2-adrenoceptor polymorphisms and asthma diagnosis among
      Mexican adults.
AB  - BACKGROUND: Recent studies demonstrate that genetic variations in the human
      beta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter
      receptor function in vitro and are associated with asthma severity and airway
      hyperresponsiveness but have not been linked to asthma diagnosis. The nature of
      the relation in a more homogeneous population is uncertain. OBJECTIVE: We
      determined frequencies of these polymorphisms to explore the association between
      beta(2)AR haplotypes and asthma diagnosis and phenotype. METHODS: This is a
      population-based, case-control study that involves a total sample of 907
      unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase
      chain reaction-restriction fragment length polymorphism analysis. Multivariate
      logistic regression analysis was used to estimate the odds ratio (OR) of the
      association between beta(2)AR haplotype status and asthma diagnosis. RESULTS: A
      significant inverse association was found between subjects with Glu27 allele (OR,
      0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8)
      and asthma. Sex differences in this association were explored, given the complex
      relation between sex and asthma. Among men, a positive association was present
      between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and
      asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27
      alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the
      Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). CONCLUSIONS: Variation in the
      beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease
      modifier in nocturnal asthma.

PMID- 14657866
TI  - Maternal sex hormones in early pregnancy and asthma among offspring: a case
      control study.
AB  - BACKGROUND: Sex hormones may be associated with the risk of onset of asthma.
      OBJECTIVE: To study the association between maternal sex hormone concentrations
      during early pregnancy and the risk of asthma among offspring. METHODS: A case
      control study of 129 asthmatic children and 125 control children 5 to 6 years of
      age. Maternal sera in early pregnancy were obtained from the Finnish Maternal
      Cohort serum bank. RESULTS: The means of serum progesterone and estradiol and
      free estradiol in mothers of asthmatic and control children were 81.0 and 82.8
      nmol/L (P =.60), 7.87 nmol/L and 7.65 nmol/L (P =.99), and 149.5 pmol/L and 148.0
      pmol/L (P =.95), respectively. There were also no differences in the mean
      concentrations of maternal sex hormones according to the presence of allergic
      rhinitis or atopic eczema among the children. CONCLUSIONS: The current results do
      not support an association between maternal sex hormone concentrations during
      early pregnancy and onset of allergic disease in early childhood.

PMID- 14657867
TI  - Incidence of occupational rhinoconjunctivitis and risk factors in animal-health
      apprentices.
AB  - BACKGROUND: Exposure to laboratory animals often causes the appearance of
      immunologic sensitization and symptoms. OBJECTIVE: Our aim was to determine the
      incidence of occupational rhinoconjunctivitis and the timing of symptoms and
      their determinants in apprentices starting exposure to laboratory animals.
      METHODS: Data from 387 (92.8%) of 417 students entering career programs in animal
      health in 5 schools were kept for analysis. Questionnaires and skin prick tests
      with common and occupational inhalants were carried out on entry and at follow-up
      visits scheduled at 8, 20, 32, and 44 months, depending on the schools.
      Responsiveness to inhaled methacholine was assessed at entry. RESULTS: Ninety
      three (24%) subjects showed incident occupational rhinoconjunctivitis symptoms,
      and 37 (9.6%) had symptoms combined with skin sensitization to an animal-derived
      allergen. Symptoms such as sneezing, rhinorrhea, and itchy eyes tended to develop
      early in the course of exposure. In two thirds of the subjects, symptoms
      persisted at subsequent visits. In a multivariate analysis the determinants of
      the appearance of rhinoconjunctivitis with or without allergic sensitization
      included sensitization to grass pollens (odds ratio [OR], 1.78; 95% CI, 0.99
      3.19), as well as nasal (rhinorrhea in contact with dust: OR, 1.79; 95% CI, 1.05
      3.05) and bronchial symptoms (chest tightness: OR, 3.31; 95% CI, 0.98-11.25;
      cough on exposure to strong odors: OR, 1.88; 95% CI, 0.98-3.59). CONCLUSION: The
      incidence of occupational rhinoconjunctivitis symptoms with or without
      immunologic sensitization is high in apprentices starting exposure to laboratory
      animals. Symptoms related to histamine release are common in the early course of
      exposure. Determinants include immunologic and target-organ susceptibility.

PMID- 14657869
TI  - Cockroach proteases increase IL-8 expression in human bronchial epithelial cells
      via activation of protease-activated receptor (PAR)-2 and extracellular-signal
      regulated kinase.
AB  - BACKGROUND: We have shown that serine proteases in German cockroach extract
      increase TNF-alpha-induced expression of IL-8 in human bronchial epithelial
      cells. The mechanism by which cockroach proteases regulate cytokine expression is
      unknown; however, protease-activated receptors (PARs) might play a role.
      OBJECTIVE: We sought to determine the role of PARs and extracellular-signal
      regulated kinase (ERK) in cockroach-induced regulation of IL-8 expression.
      METHODS: 16HBE14o- human bronchial epithelial cells were treated with the
      specific PAR-1 and PAR-2 agonists, TFRIFD and SLIGKV, respectively. IL-8
      transcription was assessed by transiently transfecting cells with a luciferase
      tagged IL-8 promoter construct, and in some cases, dominant-negative expression
      vectors. To block PAR cleavage, antibodies against the cleavage region of PAR-1
      and PAR-2 were used. ERK phosphorylation was determined by Western blot. RESULTS:
      Although both PAR-1 and PAR-2 were endogenously expressed in 16HBE14o- cells,
      selective activation of PAR-2 but not PAR-1 mimicked the effect of cockroach
      extract on IL-8 expression. Using a blocking antibody against cleavage of PAR-2
      but not PAR-1 attenuated cockroach-extract-induced responses, suggesting that
      cockroach proteases cleave PAR-2. Treatment of cells with cockroach extract and
      SLIGKV each increased phosphorylation of ERK. Chemical or genetic inhibition of
      Ras and mitogen-activated protein kinase/ERK (MEK), upstream activators of ERK,
      each attenuated cockroach- and PAR-2-induced IL-8 transcription. CONCLUSION:
      Cockroach proteases and PAR-2 activation synergistically increase TNF-alpha
      induced IL-8 transcription via activation of ERK. These data suggest an important
      role for PAR-2 and ERK activation in the regulation of cytokine expression in
      airway epithelium in response to cockroach proteases.

PMID- 14657870
TI  - FcepsilonRI-dependent gene expression in human mast cells is differentially
      controlled by T helper type 2 cytokines.
AB  - BACKGROUND: Mast cells (MCs) proliferate in response to T(H)2 cytokines and
      express genes de novo after activation. Limited information is available
      concerning the interplay between these events. OBJECTIVE: We explored the
      potential for T(H)2 cytokines to alter activation-dependent gene expression by
      MCs. METHODS: Cord blood-derived human (h)MCs maintained in stem cell factor
      (SCF) alone were compared with replicates treated with IL-4, IL-5, or IL-9,
      respectively, for their patterns of FcepsilonRI-dependent gene induction using
      microarray technology. RESULTS: Activation of SCF-treated hMCs upregulated their
      expression of roughly 140 transcripts at 2 hours, including genes involved in
      cell cycle progression and arrest. Each cytokine substantially modified this
      profile; approximately 800 inducible genes apiece were controlled by IL-5 or IL
      9, whereas 169 inducible genes were controlled by IL-4. IL-4 favored the
      induction of cytokines and of genes associated with cell growth arrest (GADD34,
      GAS-1, CIDE-A, INK4D, and BAX) and completely abolished the enhanced
      proliferation observed in the other 3 groups after activation. Conversely, IL-5
      priming induced preferential upregulation of genes involved in cell proliferation
      and did not abolish thymidine incorporation. CONCLUSIONS: T(H)2 cytokines
      differentially modulate gene induction in hMCs after FcepsilonRI cross-linkage.
      IL-4 uniquely controls cytokine gene expression by hMCs and might also limit
      their activation-driven proliferation.

PMID- 14657871
TI  - High contribution contrast between the genes of eosinophil peroxidase and IL-4
      receptor alpha-chain in Japanese cedar pollinosis.
AB  - BACKGROUND: Japanese cedar pollinosis is the most common form of hayfever in
      Japan in spring and has remarkably increased since 1960. OBJECTIVE: We sought to
      clarify the candidate genes for cedar pollinosis using a case-control study.
      METHODS: After diagnosing 351 subjects on the basis of an intradermal test, nasal
      provocation test, and questionnaire regarding nasal and conjunctival symptoms, we
      determined the blood-specific IgE values and genotypes of eosinophil peroxidase
      (EPO) and interleukin-4 receptor alpha-chain (IL4RA) in 145 patients with
      pollinosis and 206 healthy subjects, including 75 healthy subjects with higher
      specific IgE values. RESULTS: We found significant differences in the frequencies
      of Pro358Leu in EPO and of Ile50Val and Glu375Ala in IL4RA between patients and
      healthy subjects. There was a significantly higher frequency of 358Leu in EPO in
      patients than in healthy subjects showing a higher specific IgE value. In
      contrast, we recognized significant changes in the prevalence of Ile50Val and
      Glu375Ala in IL4RA in healthy subjects with a normal IgE value compared with
      those in healthy subjects with a higher specific IgE value. The relationship
      between EPO polymorphisms and the onset of symptoms was exactly opposite that for
      IL4RA. CONCLUSIONS: These results suggest that Pro358Leu in EPO is strongly
      involved in the development of cedar pollinosis. Ile50Val and Glu375Ala in IL4RA
      seem to be related to cedar pollen sensitization. Subjects with Ile50 or Glu375
      might develop cedar pollinosis with increased exposure to cedar pollen.

PMID- 14657872
TI  - Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI:
      correlation with serum IgE and allergic asthma.
AB  - BACKGROUND: Type 1 dendritic cells (DC1) express the high-affinity IgE receptor
      (FcepsilonRI); however, the regulation of FcepsilonRI expression by DCs is not
      well understood. Type 2 DC (DC2) expression of FcepsilonRI has not been
      demonstrated. OBJECTIVE: We hypothesized that DC2 cellsalso express FcepsilonRI
      and that expression of FcepsilonRI by the DC1 and DC2 subsets correlates with
      serum IgE and allergic asthma disease status. METHODS: To test these hypotheses,
      we quantitated FcepsilonRI alpha chain expression by the peripheral blood
      precursor DC1 (pDC1) and pDC2 subsets by using flow cytometry. RESULTS:
      FcepsilonRI was expressed by the pDC1 and pDC2 subsets, as well as tissue DCs
      from tonsils. Relative FcepsilonRI expression by basophil, pDC1, and pDC2 subsets
      was 12:6.5:1, respectively. In both pDC subsets, FcepsilonRI expression was
      significantly greater in allergic asthmatic subjects than in nonatopic control
      subjects. pDC1 and pDC2 expression of FcepsilonRI was highly correlated to serum
      IgE concentration. The pDC1, pDC2, and basophil subsets demonstrated a similar
      magnitude of increase in FcepsilonRI expression relative to changes in serum IgE.
      CONCLUSIONS: FcepsilonRI expression is characteristic of both the DC1 and DC2
      subsets. Furthermore, FcepsilonRI expression by these cells is highly correlated
      to serum IgE and to basophil FcepsilonRI expression and is greater in subjects
      with allergic asthma. These data support the concept that novel therapeutic
      approaches directly targeted at FcepsilonRI expression would affect both the
      sensitization and the effector phases of the allergen-specific immune response.

PMID- 14657873
TI  - The CX3C chemokine fractalkine in allergic asthma and rhinitis.
AB  - BACKGROUND: Unlike other chemokines, fractalkine is expressed as a membrane-bound
      form, mainly on endothelial and epithelial cells, and can be shed as a soluble
      chemotactic form. Fractalkine can capture leukocytes expressing its receptor
      (CX(3)CR(1)), including T lymphocytes, rapidly and firmly in an integrin
      independent manner. Because of its dual activity, fractalkine plays a major role
      in the transendothelial and transepithelial migration of leukocytes during
      inflammation. OBJECTIVE: We sought to study the fractalkine-CX(3)CR(1) axis in
      patients with allergic airways diseases. METHODS: Plasma fractalkine levels were
      measured by means of ELISA in 19 control subjects and 55 patients with
      symptomatic allergic rhinitis, asthma, or both, and CX(3)CR(1) function was
      studied by using triple-color flow cytometry in circulating T-lymphocyte
      subpopulations. Segmental allergen challenge was performed in 16 allergic
      asthmatic patients to analyze fractalkine expression and inflammatory cell
      recruitment in bronchoalveolar lavage fluid and bronchial biopsy specimens.
      RESULTS: Compared with control subjects, patients with symptomatic allergic
      rhinitis and asthmatic patients had increased circulating fractalkine levels, and
      CX(3)CR(1) function was upregulated in circulating CD4(+) T lymphocytes. Twenty
      four hours after segmental allergen challenge, bronchoalveolar lavage fluid
      soluble fractalkine concentrations increased and correlated with the total number
      of recruited cells. Bronchial epithelial and endothelial cells expressed high
      levels of the membrane-bound form of fractalkine before and after challenge.
      CONCLUSION: Allergic asthma and rhinitis are associated with systemic and
      bronchial upregulation of the chemotactic axis fractalkine-CX(3)CR(1). This might
      contribute to the rapid recruitment of circulating CD4(+) T lymphocytes in the
      airways after allergen stimulation.

PMID- 14657874
TI  - Omalizumab treatment downregulates dendritic cell FcepsilonRI expression.
AB  - BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells that
      express FcepsilonRI, the high-affinity IgE receptor. Although the downregulation
      of basophil FcepsilonRI during anti-IgE therapy with omalizumab is well
      documented, its effect on FcepsilonRI expression by DCs has not been reported.
      OBJECTIVE: We hypothesized that IgE regulates surface FcepsilonRI expression by
      DCs in vivo and that, consequently, anti-IgE therapy decreases FcepsilonRI
      expression by DCs. METHODS: In a randomized, double-blind, placebo-controlled
      clinical trial 24 subjects (16 receiving omalizumab and 8 receiving placebo) with
      seasonal allergic rhinitis received the study drug on days 0 and 28. Serial blood
      samples drawn on days 0, 7, 14, 28, and 42 were analyzed for precursor DC1 (pDC1)
      and pDC2 surface expression of FcepsilonRIalpha by using flow cytometry. RESULTS:
      Omalizumab caused a significant decrease in surface FcepsilonRI expression at all
      time points examined in both the pDC1 and pDC2 subsets. No significant change was
      seen with placebo. The maximum decrease in FcepsilonRI expression in the
      omalizumab group was 52% and 83%, respectively, for the pDC1 and pDC2 subsets.
      The decrease in FcepsilonRI expression by both pDC subsets correlated with the
      decrease in serum-free IgE and was of a similar magnitude to that found in
      basophils. A 10-fold decrease in IgE corresponded to a 42% and 54% decrease in
      surface FcepsilonRI expression by the pDC1 and pDC2 subsets, respectively.
      CONCLUSION: These results demonstrate that anti-IgE therapy causes a rapid
      decrease in DC surface FcepsilonRI expression and establish that IgE is an
      important regulator of FcepsilonRI expression by DCs.

PMID- 14657875
TI  - Adenoid-derived TH2 cells reactive to allergen and recall antigen express CC
      chemokine receptor 4.
AB  - BACKGROUND: Interrupting recruitment of allergen-specific T(H)2 cells to the
      airway is an attractive potential therapeutic strategy for allergic disease. CC
      chemokine receptor 4 (CCR4) is preferentially expressed on T(H)2 cells, and CCR4
      expressing cells have been described at sites of allergic inflammation. However,
      whether selective recruitment of allergen-specific T(H)2 cells to the airways
      occurs through CCR4 or other chemokine receptors remains controversial.
      OBJECTIVE: We investigated the expression of the T(H)2-associated chemokine
      receptors (CCR3, CCR4, and CCR8) by primary antigen-specific human airway T(H)2
      cells. METHODS: Children undergoing elective adenoidectomy were recruited, and
      their atopic status was determined. Adenoid cells were cultured with allergen or
      recall antigen. Flow cytometric analyses permitted identification of T(H) cells
      proliferating in response to antigen and characterization of chemokine receptor
      and cytokine expression. RESULTS: An increased proportion of airway CD4(+) T
      cells proliferated to allergen in atopic children (n = 6, of which 4 were given
      diagnoses of asthma or rhinitis) compared with nonatopic children (P =.0004).
      These cells were 44.7% (32.6% to 50.0%) IL-4(+) and only 2.5% (0.6% to 3.3%) IFN
      (gamma) and showed a greater than 5-fold upregulation of CCR4 expression to 54.0%
      (40.7% to 67.8%) after culture, whereas CCR3 was expressed on 9.7% (7.4% to
      18.9%) of allergen-reactive cells and CCR8 on less than 1%. Interestingly,
      increased expansion of recall antigen-specific cells was also seen in atopic
      children, and these cells were also predominantly of a T(H)2 CCR4(+) phenotype.
      CONCLUSION: We conclude that airway allergen-specific T(H)2 cells are CCR4(+),
      but in the atopic child CCR4 does not distinguish between recall antigen and
      allergen specificity.

PMID- 14657877
TI  - Gene expression analysis in mastocytosis reveals a highly consistent profile with
      candidate molecular markers.
AB  - BACKGROUND: Mastocytosis is a rare clonal disorder that might be accompanied by
      non-mast-cell clonal hematologic disorders, such as myeloproliferative or
      myelodysplastic syndromes. OBJECTIVE: Our aim was to further understand the
      pathologic basis of mastocytosis and to identify novel molecular markers of
      disease. METHODS: Microarray analysis was performed on RNA preparations obtained
      from bone marrow mononuclear cells of patients with mastocytosis. Results were
      compared with gene expression profiles performed on bone marrow mononuclear cells
      of healthy subjects. RESULTS: Analysis of gene expression in neoplastic bone
      marrow tissues revealed highly consistent profiles. One hundred four genes were
      significantly upregulated, and 64 genes were significantly downregulated in the
      bone marrow of patients with mastocytosis. The most prominent differentially
      expressed gene was alpha-tryptase (44.6-fold increase). Also upregulated were
      genes involved in cell proliferation, neoplastic transformation, and apoptosis.
      Both hierarchical and K-means clustering analyses identified an identical group
      of 10 genes highly coordinately overexpressed in patients with mastocytosis,
      including genes for the mast-cell-associated enzymes alpha- and beta-tryptase and
      carboxypeptidase A. The expression level of 3 of these 10 genes (alpha-tryptase,
      the activating transcription factor type 3, and the muscle aponeurotic
      fibrosarcoma type F oncogene) was significantly correlated with serum tryptase
      levels, a surrogate marker of disease. CONCLUSION: The data presented in this
      study reveal significant differences in gene expression in the bone marrow of
      patients with mastocytosis compared with healthy subjects, demonstrate highly
      coordinated genes that might contribute to pathology, and identify 3 genes as
      candidate molecular markers for systemic disease.

PMID- 14657878
TI  - In vitro allergen-induced mRNA expression of signaling lymphocytic activation
      molecule by PBMC of patients with allergic rhinitis is increased during specific
      pollen immunotherapy.
AB  - BACKGROUND: Specific immunotherapy (SIT) acts by inducing a shift from T(H)2 to
      T(H)1 cell response on mucous membranes, reducing allergic inflammation. New
      genes expressed primarily in T(H)1-type cells have been found. Of these genes,
      signaling lymphocytic activation molecule (SLAM) promotes T-cell proliferation
      and IFN-gamma production. Nothing is known about its role in T(H)2-T(H)1 switch
      during SIT. OBJECTIVE: We sought to analyze the mRNA expression of SLAM and other
      T(H)1-associated genes, interleukin-12 receptor beta2 (IL-12Rbeta2) and T-box
      expressed in T cells (T-bet), and compare them with the clinical outcome of the
      therapy. METHODS: PBMC from 30 patients allergic to pollen undergoing SIT were
      collected during the therapy. Control PBMC were collected from 10 patients with
      allergic rhinitis not participating in SIT and from 10 nonallergic subjects.
      Cells were stimulated in vitro with pollen allergen extracts. SLAM, IL-12Rbeta2,
      and T-bet mRNA expressions were studied by real-time quantitative RT-PCR
      technique (Taqman). Symptom scoring and medication scoring were registered before
      commencement of SIT and after 1 year of the therapy. RESULTS: Before the
      treatment, in vitro allergen-induced SLAM mRNA expression in PBMC was
      significantly lower in the patients with allergic rhinitis than in the healthy
      control subjects. After 1 year of the treatment, SLAM mRNA expression was
      increased in the patients undergoing SIT and was associated with IFN-gamma mRNA
      expression and inversely associated with the symptom improvement. At the
      maintenance dose, an increase in SLAM mRNA expression was associated with the
      clinical symptom improvement at 1 year. No changes were seen in IL-12Rbeta(2) or
      T-bet mRNA expressions. CONCLUSIONS: SLAM mRNA expression in PBMC is modulated
      during the course of SIT, and an early and transient increase of SLAM mRNA
      expression is associated with clinical symptom improvement.

PMID- 14657879
TI  - Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune
      responses and clinical outcomes in infants at high risk of atopy: a randomized,
      controlled trial.
AB  - BACKGROUND: There is growing interest in the potential role of anti-inflammatory
      n-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of allergic
      disease. OBJECTIVE: We sought to determine whether maternal dietary
      supplementation with n-3 PUFAs during pregnancy could modify immune responses in
      infants. METHODS: In a randomized, controlled trial 98 atopic, pregnant women
      received fish oil (3.7 g n-3 PUFAs per day) or placebo from 20 weeks' gestation
      until delivery. Neonatal PUFA levels and immunologic response to allergens were
      measured at birth. RESULTS: Eighty-three women completed the study. Fish oil
      supplementation (n = 40) achieved significantly higher proportions of n-3 PUFAs
      in neonatal erythrocyte membranes (mean +/- SD, 17.75% +/- 1.85% as a percentage
      of total fatty acids) compared with the control group (n = 43, 13.69% +/- 1.22%,
      P <.001). All neonatal cytokine (IL-5, IL-13, IL-10, and IFN-gamma) responses (to
      all allergens) tended to be lower in the fish oil group (statistically
      significant only for IL-10 in response to cat). Although this study was not
      designed to examine clinical effects, we noted that infants in the fish oil group
      were 3 times less likely to have a positive skin prick test to egg at 1 year of
      age (odds ratio, 0.34; 95% confidence interval, 0.11 to 1.02; P =.055). Although
      there was no difference in the frequency of atopic dermatitis at 1 year of age,
      infants in the fish oil group also had significantly less severe disease (odds
      ratio, 0.09; 95% confidence interval, 0.01 to 0.94; P =.045). CONCLUSIONS: These
      data suggest a potential reduction in subsequent infant allergy after maternal
      PUFA supplementation. More detailed follow-up studies are required in larger
      cohorts to establish the robustness of these findings and to ascertain their
      significance in relation to longer-term modification of allergic disease in
      children.

PMID- 14657880
TI  - Concurrent presence of agonistic and antagonistic anti-CD95 autoantibodies in
      intravenous Ig preparations.
AB  - BACKGROUND: Although there have been several reports suggesting the presence of
      physiologic anti-CD95 (Fas, APO-1) autoantibodies in human intravenous Ig (IVIg)
      preparations, it is still unclear whether and under which conditions these
      autoantibodies block or stimulate the CD95 receptor. OBJECTIVE: We examined the
      effects of IVIg on CD95-mediated apoptosis in CD95-sensitive human blood
      neutrophils in vitro. METHODS: The presence of anti-CD95 antibodies was
      determined by competition assays with flow cytometry. Cell death and apoptosis
      were assessed by ethidium bromide uptake test and annexin V staining,
      respectively. RESULTS: Pretreatment of neutrophils with IVIg prevented binding of
      FITC-conjugated anti-CD95 mAb to the cell surface, suggesting that IVIg contains
      CD95 autoantibodies. By using low concentrations of IVIg (1 to 10 mg/mL), we
      observed a dose-dependent inhibition of anti-CD95 mAb (CH11)-mediated neutrophil
      apoptosis. Higher concentrations of IVIg (20 to 50 mg/mL), however, induced
      neutrophil death and apoptosis in a dose-dependent manner. This effect was
      partially blocked by soluble CD95 receptors (recombinant Fc-Fas) but not by an
      anti-CD95 blocking mAb, which was shown to recognize the CH11 epitope of CD95.
      CONCLUSION: Both agonistic and antagonistic anti-CD95 antibodies are present in
      IVIg, and the effect on CD95 is dose-dependent. Our findings have potential
      implications for IVIg treatment, which is intended to target the CD95 receptor.

PMID- 14657881
TI  - Association of allergic contact dermatitis with a promoter polymorphism in the
      IL16 gene.
AB  - BACKGROUND: There is evidence that IL-16, a cytokine that induces chemotactic
      responses in CD4(+) T cells, eosinophils, and dendritic cells, plays an important
      role during different types of cutaneous inflammatory responses, including
      allergic contact dermatitis (ACD) and atopic dermatitis (AD). OBJECTIVES: We
      sought to test for association between a promoter polymorphism in the IL16 gene
      (T to C transition at position -295) and ACD and AD, respectively. METHODS: IL16 
      295 genotypes were determined in samples from 2 separate case-control studies
      with white individuals. The first study included healthy individuals (n = 310)
      and patients with ACD (n = 86). These patients were polysensitized as defined by
      a contact sensitization to para-substituted aryl compounds and at least one other
      structurally unrelated allergen. The second study comprised healthy subjects (n =
      214) and patients with AD (n = 94). RESULTS: IL16 -295 genotypes were differently
      distributed among polysensitized and healthy control subjects (P =.0021). In
      particular, the IL16 -295*C/C genotype was overrepresented among polysensitized
      individuals (7.0% vs 1.0% in the control group; odds ratio, 7.68; 95% CI, 1.59
      48.12). In contrast, there was no evidence for an association between the IL16 
      295 polymorphism and AD. CONCLUSION: The IL16 -295 promoter polymorphism might
      influence susceptibility to contact allergy.

PMID- 14657882
TI  - Distinct patterns of gene expression in the skin lesions of atopic dermatitis and
      psoriasis: a gene microarray analysis.
AB  - BACKGROUND: Atopic dermatitis (AD) and psoriasis are the two most common chronic
      inflammatory skin diseases. Both of these diseases have distinct clinical
      findings and specific inflammatory cell infiltrates. Previous reports have
      focused individually on one or two genes or gene products in the lesions of both
      skin diseases. However, they have not captured the complex gene expression that
      must occur to induce specific cellular infiltrates in the skin lesions of these
      two diseases. DNA microarray studies allow the simultaneous comparison of
      thousands of messenger RNAs that may identify the disease-specific pattern of
      tissue inflammatory responses. OBJECTIVE: To compare the complex gene expression
      pattern of AD versus psoriasis skin lesions. METHODS: RNA was extracted from skin
      biopsy specimens of 6 patients with AD and 7 patients with psoriasis and analyzed
      with the use of Hu-U95Av.GeneChip microarrays. To confirm GeneChip results, real
      time PCR of selected genes were performed. RESULTS: In AD skin, a total of 18
      genes including the CC chemokines, CCL-13/MCP-4, CCL-18/PARC, and CCL-27/CTACK
      showed a statistically significant, >2-fold increase of gene expression compared
      with psoriasis. In psoriasis skin, a total of 62 genes including CCL-4/MIP-1beta,
      CCL-20/MIP-3alpha, CXCL-2/GRO-beta CXCL-8/IL-8, and CXCR2/IL-8R showed a >2-fold
      increase of gene expression compared with AD skin. Real-time PCR confirmed
      several of these GeneChip results. CONCLUSIONS: These results show a very
      distinctive gene expression pattern in AD as compared with psoriasis that may
      explain several features of AD and psoriasis including the specific inflammatory
      cell infiltrates observed in these disorders, that is, T(H)2 cells, eosinophils,
      and mast cells in AD and T(H)1 cells and neutrophils in psoriasis. Such
      observations may contribute to a characteristic "signature" for these two skin
      diseases.

PMID- 14657884
TI  - Prevalence of peanut and tree nut allergy in the United States determined by
      means of a random digit dial telephone survey: a 5-year follow-up study.
AB  - BACKGROUND: Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal
      and near-fatal food allergic reactions. Peanut allergy appears to be increasing
      in prevalence. OBJECTIVES: We sought to determine the prevalence of self-reported
      peanut and TN allergy among the general population of the United States in 2002
      by sex and age and to compare the results with prevalence estimates obtained 5
      years earlier. METHODS: We performed a nationwide, cross-sectional, random
      telephone survey by using a standardized questionnaire. RESULTS: A total of 4855
      households participated (53% participation rate), representing a census of 13,493
      individuals. Peanut allergy, TN allergy, or both was self-reported in 166 (1.2%;
      95% CI, 1.0%-1.4%) individuals in 155 (3.2%; 95% CI, 2.7%-3.7%) households,
      overall prevalence rates similar to those reported in 1997. Also similar to the
      1997 survey, the severity level was high, with 79% reporting respiratory or
      multiple organ system reactions and 66% experiencing more than 5 lifetime
      reactions. Despite the severity and reaction frequency, only 74% of the children
      and 44% of the adults sought evaluation for the allergy, and fewer than half who
      did were prescribed self-injectable epinephrine. Applying conservative rules to
      adjust for persons with unconvincing reactions and a false-positive rate of the
      survey instrument (7%), a final prevalence estimate of 1.04% (95% CI, 0.9%-1.24%)
      was obtained. A male predominance of peanut-TN allergy was reported in children
      younger than 18 years (1.7% vs 0.7%, P =.02), and a female predominance was
      reported among adults (1.7% vs 0.9%, P =.0008). Although the rate of peanut
      allergy, TN allergy, or both was not significantly different from 1997 to 2002
      among adults, the rate increased from 0.6% to 1.2% among children, primarily as a
      result of an increase in reported allergy to peanut (0.4% in 1997 to 0.8% in
      2002, P =.05). CONCLUSIONS: Self-reported peanut allergy has doubled among
      children from 1997 to 2002, and peanut allergies, TN allergies, or both continue
      to be reported by more than 3 million Americans. Considering that reactions are
      severe and the allergy is persistent, these allergies represent an increasing
      health concern.

PMID- 14657885
TI  - Len c 1, a major allergen and vicilin from lentil seeds: protein isolation and
      cDNA cloning.
AB  - BACKGROUND: Lentils are among the main plant foods causing allergic reactions in
      pediatric patients in the Mediterranean area and in many Asian communities.
      However, very few reports have been devoted to identifying lentil allergens. Seed
      storage proteins of the vicilin family have been characterized as major allergens
      in several seed legumes and tree nuts. OBJECTIVE: We sought to evaluate the role
      of lentil vicilins as food allergens. METHODS: A serum pool and individual sera
      from 22 patients with lentil allergy were used in different IgE-binding assays.
      Mature lentil vicilin was isolated by means of cation-exchange chromatography,
      followed by reverse-phase HPLC, and characterized by means of N-terminal amino
      acid sequencing, matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI) analysis, complex asparagine-linked glycan detection, specific IgE
      immunodetection with individual sera, and ELISA inhibition assays. Complete cDNAs
      encoding lentil vicilin variants were isolated by means of PCR with primers based
      on the amino acid sequence of the allergen. RESULTS: A major IgE-binding
      component of approximately 50 kd was detected in lentil extracts. This component
      was isolated and characterized, showing a single N-terminal amino acid sequence
      homologous to those of legume vicilins and a broad peak (maximum at 48613 d) in
      MALDI analysis. The purified allergen was recognized by 77% (17/22) of the
      individual sera from patients with lentil allergy and reached up to 65%
      inhibition of the IgE binding to the crude lentil extract. The allergen showed 3
      isoforms varying in their degree of N-glycosylation. Two cDNA clones encoding
      different allergen variants were isolated. The amino acid sequences deduced from
      both clones (415 and 418 residues; 47.4 and 47.8 kd) showed greater than 50%
      identity with major peanut (Ara h 1) and soybean (conglutinin subunits) allergens
      belonging to the vicilin family. Furthermore, these sequences included those of
      the previously characterized lentil allergen Len c 1.02 (108 amino acid residues
      of the C-terminal domain) and those of a novel lentil IgE-binding protein of 26
      kd. CONCLUSION: The mature 48-kd lentil vicilin, designated Len c 1.01, is a
      major allergen. Two of its processing fragments, corresponding to subunits of 12
      to 16 kd (previously named Len c 1) and 26 kd, are also relevant lentil IgE
      binding proteins. The sequence homology of Len c 1.01 to those of major allergens
      from peanut, soybean, walnut, and cashew can help to investigate potential cross
      reactions among these plant foods.

PMID- 14657886
TI  - Immunostimulatory potential of beta-lactoglobulin preparations: effects caused by
      endotoxin contamination.
AB  - BACKGROUND: The immunomodulating potential residing in cow's milk proteins is
      currently receiving increasing attention because of growing interest in
      functional foods and the complex problem of cow's milk allergy. One of the major
      cow's milk allergens, whey protein beta-lactoglobulin, has previously been shown
      to mediate cellular activation in both human and murine immune cells. OBJECTIVE:
      We examined the response to different beta-lactoglobulin preparations in naive
      immune cells. METHODS: Splenocytes and cells from mesenteric lymph nodes derived
      from BALB/c mice bred and maintained on a milk-free diet were cultured in vitro
      with different beta-lactoglobulin preparations. Cell proliferation, cytokine
      production, and increases in intracellular glutathione were used as cellular
      activation markers. Moreover, the effect of beta-lactoglobulin on cytokine
      production in murine bone-marrow-derived dendritic cells was examined. RESULTS:
      We observed that some commercial beta-lactoglobulin preparations induced
      pronounced proliferation of both spleen cells and cells from mesenteric lymph
      nodes; production of TNF-alpha, IL-6, IL-1beta, and IL-10; and an increased level
      of intracellular glutathione in spleen cell cultures. Furthermore, TNF-alpha, IL
      6, IL-1beta, and IL-10 production was induced in murine bone-marrow-derived
      dendritic cells. Purification of beta-lactoglobulin from raw milk using
      nondenaturating conditions, however, revealed that the beta-lactoglobulin per se
      did not possess the immunomodulatory activity. Eventually, the immunostimulatory
      effect was found to be caused by endotoxin contamination. CONCLUSION: These
      results identify endotoxin as the main immunostimulatory component present in
      some commercial beta-lactoglobulin preparations. Moreover, the present study
      makes it evident that immunomodulatory effects attributed to beta-lactoglobulin
      need to be reassessed.

PMID- 14657887
TI  - Prevalence of peanut allergy in primary-school children in Montreal, Canada.
AB  - BACKGROUND: Peanut allergy is receiving increasing attention. Only one study has
      estimated the prevalence in North America, but it did not corroborate history
      with diagnostic testing. OBJECTIVE: We estimated the prevalence of peanut allergy
      in Montreal by administering questionnaires regarding peanut ingestion to
      children in kindergarten through grade 3 in randomly selected schools. METHODS:
      Respondents were stratified as follows: (1). peanut tolerant, (2). never-rarely
      ingest peanut, (3). convincing history of peanut allergy, and (4). uncertain
      history of peanut allergy. Groups 2, 3, and 4 underwent peanut skin prick tests
      (SPTs), and if the responses were positive in groups 2 or 4, measurement of
      peanut-specific IgE were undertaken. Children in group 3 with a positive SPT
      response were considered allergic to peanut without further testing. Children in
      groups 2 and 4 with peanut-specific IgE levels of less than 15 kU/L underwent
      oral peanut challenges. RESULTS: Of the 7768 children surveyed, 4339 responded,
      94.6% in group 1. The prevalence of peanut allergy was 1.50% (95% CI, 1.16%
      1.92%). When multiple imputation was used to incorporate data on those responding
      to the questionnaire but withdrawing before testing, the estimated prevalence
      increased to 1.76% (95% CI, 1.38%-2.21%). When data regarding the peanut allergy
      status of nonresponders (as declared to the school before the study) were also
      incorporated, the estimated prevalence was 1.34% (95% CI, 1.08%-1.64%).
      CONCLUSION: Our prevalence study is the first in North America to corroborate
      history with confirmatory testing and the largest worldwide to incorporate these
      techniques. We have shown that, even with conservative assumptions, prevalence
      exceeds 1.0%.

PMID- 14657888
TI  - Cost-effectiveness analysis of early intervention with budesonide in mild
      persistent asthma.
AB  - BACKGROUND: The Inhaled Steroid as Regular Therapy in Early Asthma (START) study
      reported that early intervention with budesonide in mild persistent asthma
      reduces severe asthmatic events and improves symptom outcomes and lung function
      in adults and children. OBJECTIVE: We sought to estimate the incremental cost
      effectiveness of early intervention with budesonide, as observed within the START
      study. METHODS: START was a randomized, 3-year controlled trial of budesonide in
      early onset mild asthma among 7165 subjects ages 5 to 66 years. Three age groups
      (5-10, 11-17, and >or=18 years) were studied separately and overall. Differences
      in the probability of emergency treatments, symptom-free days (SFDs), and costs
      of health care were determined. Incremental cost-effectiveness ratios were
      estimated from the health care payer and societal perspectives. RESULTS: Compared
      with usual therapy, patients receiving budesonide experienced an average of 14.1
      (SE, 1.3) more SFDs per year (P <.001), fewer hospital days (69%, P <.001), and
      fewer emergency department visits (67%, P <.05). From the health care payer
      perspective, the net cost of early use of budesonide was an additional US dollars
      0.42 (SE, dollars 0.04) per day, and the resultant cost-effectiveness ratio was
      US dollars 11.30 (95% CI, US dollars 8.60-US dollars 14.90) per SFD gained. From
      the societal perspective, the cost offsets of lower absence from school or work
      reduced the net cost of early budesonide to US dollars 0.14 (SE, US dollars 0.07)
      per day and decreased the cost-effectiveness ratio to US dollars 3.70 (95% CI, US
      dollars 0.10-US dollars 8.00). Early intervention was more effective and cost
      saving in the youngest age group. CONCLUSION: Long-term treatment with budesonide
      appears to be cost-effective in patients with mild persistent asthma of recent
      onset.

PMID- 14657889
TI  - High-dose intravenous glucocorticoid therapy abrogates circulating dendritic
      cells.

PMID- 14657890
TI  - Woven material for bed encasement prevents mite penetration.

PMID- 14657891
TI  - Low-dose airborne endotoxin exposure enhances bronchial responsiveness to inhaled
      allergen in atopic asthmatics.

PMID- 14657892
TI  - Applying stereology to measure thickness of the basement membrane zone in
      bronchial biopsy specimens.

PMID- 14657893
TI  - In response to a position paper of the antihistamine impairment roundtable.

PMID- 14657895
TI  - Loveless on wasp venom allergy and immunity- part 1.

PMID- 14657896
TI  - Loveless on wasp venom allergy and immunity. Part 2. The contribution of Dr Mary
      Hewitt Loveless to the management of allergy to insect stings.

PMID- 14657904
TI  - Lipid metabolism and hemocoagulation in patients with atherosclerotic stenosis of
      the extracranial arteries.
AB  - Lipid metabolism, lipid peroxidation and hemocoagulation were studied in 276
      patients with ischemic brain disease which developed due to atherosclerotic
      stenoses of the extracranial cerebral arteries (ECA). The main biochemical
      parameters were evaluated bearing in mind to the severity of vascular and
      ischemic lesion of the brain. It has been revealed as s result that the rise of
      the degree of arterial stenosis correlates well with the growth of the content of
      atherogenic lipoproteins and of the atherogenicity index. Total cholesterol (Chs)
      and low density lipoproteins (LDL) have a greater effect in the early disease
      stages whereas the high triglyceride content combined with LDL plays a relatively
      more important part in the late stages of vascular lesion. Both medium and high
      degree stenoses of the ECA are associated with a significant increase in the
      activity of lipid peroxidation and the build up of the number of primary products
      of free radical oxidation in the overwhelming majority of patients. Changes in
      the hemostatic system toward hyper-coagulation are associated with the high
      thrombotic preparedness of blood. The treatment of patients suffering from
      cerebral ischemia and atherosclerotic stenosfia of the EGA requires correction of
      the disorders in lipid metabolism, hemocoagulation and hyperreactivity of the
      vessel wall in different stages of disease.

PMID- 14657905
TI  - [Quality of life of patients with atherosclerotic lesion of lower extremity
      arteries as dependent on individual and typological properties of the patient
      personality].
AB  - Twenty men with atherosclerotic lesion of lower extremity arteries verified by
      contrast angiography and ultrasound Doppler were examined. The patients' age
      varied from 36 to 69 years (mean 57 years). Six patients had IIB ischemia, 13
      presented with degree III and one patient had degree IV ischemia according to the
      R. Fontaine classification modified by A. V. Pokrovsky. The MOS SF = 36
      questionnaire was used to estimate the quality of life of all the patients. The
      individual typological properties of the personality were defined using the
      psychodiagnostic test (PDT). A significant decrease of the patients' quality of
      life was revealed according to the scales: physical function, physical role,
      physical pain, general health condition. A correlation was recorded between the
      patient's age and the parameters of the "physical function scale" (r=-0.63;
      p<0.005). The individual typological properties of the personality exert an
      effect on five of the eight SF = 36 scales. A feedback was discovered between
      neurotism and mental health (r=-0.455; P<0.05), conscientiousness and the
      physical role (r=-0,487; p<0.05); a direct relationship was found between
      disinhibition and physical pain (r=0.451; p<0.05), general activity and physical
      pain (r=0.535; p<0.05). An indistinctly pronounced feed back manifested itself
      between the "neurotism" and "physical pain" scales (r=-0.409), "psychotism" end
      the "physical role", (r=-0.437), "introversion" and "vitality" (r=-0.408),
      "femininity" and the "emotional role" (r=-0.404), and a direct relationship was
      established between the scales "esthetic impressionability" and "vitality"
      (r=0.406).

PMID- 14657906
TI  - [Management of patients with cerebral ischemic lesions: organizational
      principles].
AB  - The paper presents general principles of care for patients with different grades
      of cerebral ischemic disorders. From total 539 patients operated in Samara
      Regional Center of Surgical Angioneurology, 87 were recruited to the study
      including 49 with preoperative ischemic stroke. The only one inclusion criterion
      was that those 87 patients were affiliated to a single community polyclinics.
      Postoperative mortality in the study group was 3.4% (3 patients). Two deaths were
      caused by recurrent intraoperative stroke, the third patient died from myocardial
      infarction 8 days after surgery. The rest 84 patients were followed up for 5
      months to 2 years. During the outpatient follow-up only 2 from 84 patients
      demonstrated cerebral transitory ischemic attacks against hypertension
      background. The study helped to elaborate general principles of care for patients
      with chronic cerebral ischemic disorders.

PMID- 14657907
TI  - [New possibilities of extremity revascularization in chronic ischemia:
      neoangiogenesis induced by exposure to high-intensive laser (an experimental
      study)].
AB  - The present work analyzes the results of an experimental study concerned with the
      treatment of chronic extremity ischemia. The experiments were carried out on 29
      mongrel dogs. Chronic ischemia of the right hind extremity was simulated in 24
      dogs (the superficial femoral artery was ligated just beneath the iliac artery
      and over its whole length as were all its collaterals). The significance of
      extremity ischemia was confirmed clinically, angiographically and
      morphologically. In the first group (19 dogs), the ischemized extremity underwent
      one month later concurrent tunneling of the femoral muscles and bone perforation
      in the diaphysis and metaphysis by exposure to high-intensive laser (Nd: YAG
      laser). The second group (5 dogs) served as control to study the response to
      ischemia. There were examined the area of laser-induced injury, the internal
      diameter of the capillaries and the diameter of muscle fibers, the specific area
      of the surface of blood vessels in the muscle and connective tissue. By the 60th
      day after exposure to laser an appreciable difference was recorded in the control
      and experimental groups: in the experimental group, angiography revealed a much
      greater number of vessels in the zone of the ligated femoral artery. Microscopy
      showed vascularized scars with muscle type arteries, active proliferation of
      endotheliocytes, formation of a new vascular bed. It is assumed that the
      tunneling of the ischemized extremity muscles concurrently with osteotrephination
      by high-intensive laser substantially restores blood flow in the distal segments
      of the ischemized extremities. Intensive development of the vascular network in
      the areas of the tunneling of the ischemized muscles of the hind extremities by
      exposure to high-intensive laser allows to compare this modality with universally
      used revascularization osteotrephination.

PMID- 14657908
TI  - [Effect of mild gravitational overload on the progression of lower limb
      arteriosclerosis obliterans].
AB  - The paper analyses the effect of mild gravitational overload (MGO) produced by
      patient's centrifugation in short-radius centrifuge in cranio-sacral orientation
      (+Gz) as a part of combined therapy for lower limb arteriosclerosis obliterans.
      Total 211 patients with I-II grade disease were divided into 3 groups: the first
      group (59 patients) was treated only by MGO, the second (100 patients) received
      both MGO and conventional conservative therapy, the third control group (52
      patients) underwent conventional therapy only. The best clinical outcome was
      achieved in the 1st and 2nd groups. Pain-free walking distance increased 2-5-fold
      (vs 1.5 in control), mean volume blood flow velocity in different arterial beds
      increased 21-33% (vs 7.5% in control), index of regional perfusion - 25-29% (vs
      10% in control), ankle-brachial index - 0.09-0.17 (vs 0.03 in control). Computer
      termography revealed recovery of leg and foot termographic picture in 86.67%,
      92.59%, and 42.86% of cases in the 1st, 2nd and 3rd groups, respectively.
      Similarly, exercise tolerance measured by bicycle ergometry increased in the 1st
      and 2nd groups 1.5-1.9-fold (mean 60-85 s) and 1.3-fold (mean 37 s) in control.
      Thus mild gravitational overload has demonstrated clinical effectiveness in
      complex therapy of lower limb arteriosclerosis obliterans.

PMID- 14657909
TI  - [Acute diffuse thrombosis of left coronary artery complicating coronary
      angioplasty].
AB  - The paper presents a case report for successful treatment of acute diffuse
      thrombosis developed in left coronary artery after coronary angioplasty fulfilled
      for 39-year-old patient with acute coronary syndrome. Heparin resistance
      accompanied by intracoronary intervention triggered severe ascending thrombosis
      of the whole anterior descending artery with involvement of circumflex artery
      ostium. Therapeutic measures included: repeated Heparin bolus injection (total
      27,000 U), bolus intracoronary Streptokinase injection (500,000 U) with
      subsequent Streptokinase infusion (1,000,000 U in 1 hour), stenting of circumflex
      artery ostium for thrombus mechanical destruction. This enabled us to restore
      adequate coronary flow and to resolve critical condition with minimal loss
      (periprocedural complication - repeated non-Q wave myocardial interfaction).

PMID- 14657910
TI  - [The use of balloon occlusion of subclavian artery defect in patients with
      traumatic injuries].
AB  - This paper analyzes an experience with the use of balloon angioplasty by means of
      the Gruntzig catheter in patients with traumatic injuries of the subclavian
      artery. The surgical technique is described as is the sequence of stages the
      basic of which are: 1) introduction of the Gruntzig catheter and its deployment
      at the site of injury; 2) angiographic diagnosis of the site of injury; 3) vessel
      immobilization and restoration of its integrity.

PMID- 14657911
TI  - [Lowering of nephropathy risk during angiography procedure. What are choice
      criteria for the radiocontrast media?].
AB  - The paper analyses current data of monomer and dimmer iodine-containing
      radiocontrast agents used for diagnosis of cardiovascular diseases and
      radiovascular interventions. Considering the risk factors of nephropathy as the
      most common and threatening complication of radiocontrast agents the authors
      conclude that non-ionic monomers are the most advisable as they demonstrate
      optimal balance of viscosity, water solubility, osmolality and diagnostic
      effectiveness.

PMID- 14657912
TI  - Thallium-199 myocardial perfusion scintigraphy in the diagnosis of restenoses
      after balloon dilatation and stenting of the coronary arteries.
AB  - AIM: To evaluate the diagnostic importance of thallium-199 myocardial perfusion
      single-photon emission computed tomography (SPECT) in the recognition of coronary
      restenoses and stenoses de novo of varying sites after endovascular treatment of
      coronary artery disease (CAD). MATERIAL AND METHODS: Myocardial perfusion
      scintigraphy was used to examine forty-six patients presenting with CAD before, 2
      3 weeks, 3-6 months and 1-2 years after balloon dilatation and/or stenting of the
      coronary arteries (CA). The presence, character and magnitude of perfusion
      defects were estimated. RESULTS: The coronary angioplasty resulted in a 76%
      decrease of the mean size of transient ischemic zones. The reversible defects of
      thallium accumulation coexisted after operation with incomplete myocardial
      revasculization in patients with hemodynamically significant multivessel lesions.
      In the long-term follow up (3-6 months and 1-2 years after endovascular
      treatment), aggravation of coronary insufficiency in patients with incomplete
      revascularization proceeded mainly due to an increase in the size of the areas
      marked by persistent disturbance of coronary microcirculation determined not only
      by acute necrotic myocardial infarction but also by transformation of transient
      ischemic zones to the new stable perfusion defects. As compared to the early
      times, the patients with verified restenoses and stenoses de novo showed in the
      later period (3-6 months after coronary angioplasty) a significant increase in
      the mean size of the transient ischemic zones, exceeding the preoperative level.
      In six of the eleven patients, the appearance of the new stable defects was
      marked after 1-2 years in the area of blood supply to the recanalized CA.
      Meanwhile the condition of myocardial perfusion in the group of patients without
      restenoses did not undergo any noticeable changes. CONCLUSION: Myocardial
      perfusion scintigraphy using thallium-199 chloride allows to objectively evaluate
      over time the results of endovascular treatment of CAD. Also, there is every
      probability of success of predicting restenoses and stenoses de novo.

PMID- 14657913
TI  - Ultrasound visualization of the popliteotibial arterial segment.
AB  - This work evaluates the diagnostic potential of color duplex scanning (CDS), as
      compared to contrast angiography, for visualization of the popliteotibial segment
      in patients with occlusive and stenotic lesions of lower extremity arteries. A
      total of 972 arterial segments were examined in 92 patients with combination of
      atherosclerosis obliterans and occlusion of the femoropopliteal segment and in 49
      patients presenting with thromboangiitis obliterans and occlusion of the
      femorotibial or tibioplantar segments. The sensitivity of CDS for different
      segments of the femoropopliteal zone constitutes 75-96%, specificity 94-100%; the
      K index 0.82-0.89.

PMID- 14657914
TI  - Shave therapy for non-healing venous trophic ulcers.
AB  - Venous trophic ulcers comprise an important social and medical problem.
      Conventional therapy includes initial healing of ulceration with consequent
      surgical intervention. Persistent or recurrent venous ulcers elicit irreversible
      changes in skin, subcutaneous fat and fasciae making impossible complete success
      of standard autodermoplasty. We present our experience in shave therapy with
      autodermoplasty and simultaneous correction of hemodynamic disturbances for this
      cohort of patients. Study results have demonstrated that in patients with chronic
      venous trophic ulcers and manifested lipodermatofasciosclerosis shave therapy
      suggests an optimal volume of intervention.

PMID- 14657915
TI  - [Formation of compressive bandage after sclerotherapy for lower limb varices].
AB  - Invention concerns compressive sclerotherapy as a treatment modality for lower
      limb varices. Technical result of investigation is the development of compressive
      bandage that creates and maintains adequate level of limb compression both in
      supine position (during bed rest) and standing or walking. Technical result is
      achieved by formation of two compressive layers of elastic bandage. Highly
      expansible elastic bandage is used for the first layer aimed for fixation and
      compression of latex or foam pads at injection sites to create local compression
      of variceal nodes. Open toe elastic stocking (I compression class) is placed over
      the bandage to maintain adequate compression during bed rest. The second external
      layer consists of elastic bandage with moderate expansion (II compression class).
      It is placed over the first one from toes to thigh upper third and creates
      optimal compression in patient's vertical position. The patient is permitted to
      take it off or loose exclusively in supine position, to wash or refresh foot with
      wet towel, to change it with a new one.

PMID- 14657916
TI  - The short-term results of internal carotid reconstructions by absorbable suture
      material.
AB  - Analysis was made of the results of 11 internal carotid reconstructions using
      polydioxanone (PDS) sutures 6 months after intervention performed in 10 patients.
      All operations on the carotid bifurcation were accomplished using 5/0 PDS
      continuous suture. Nine eversion carotid endarterectomies and 2 internal carotid
      reconstructions were performed for Kinkiking. There were no neurologic
      complications, thromboses, bleedings or repeated operations after interventions
      on the brachiocephalic arteries. Six months later the patients were examined
      under ambulatory conditions and were provided color duplex scanning (CDS) of the
      reconstructed area. Measurements were made of the diameter of the common carotid
      artery (CCA) right beneath the anastomosis between the CCA and the internal
      carotid artery (ICA), of the maximal diameter of the anastomosis between the CCA
      and the ICA, and of the size of the proximal ICA segment right the anastomosis.
      During the 6-month period following surgical intervention, all 10 patients did
      not demonstrate any ischemic attacks (TIA) or strokes. No cases of anastomotic
      aneurysms were recorded. After 9 reconstructions no ICA restenoses were marked.
      In one case, restenosis accounted for 40% because of atherosclerosis progression
      and after one operation there developed asymptomatic thrombosis of the ICA. The
      study has demonstrated that the use of PBS absorbable suture for autoarterial ICA
      reconstruction provides for anastomosis integrity minimally over the period as
      long as 6 months.

PMID- 14657917
TI  - Results of vascular reconstructions for a associated lesion of the
      brachiocephalic arteries and paroxysmal disorders of cardiac rhythm.
AB  - Annually, about 400,000 new patients with strokes are recorded in Russia. Of
      these, 80% of patients may develop ischemic brain infarctions. In approximately
      30-40% of cases, ischemic lesion of the brain eventuates in lethal outcome; the
      same number of patients remain heavily disabled and only 15-20% of patients
      return to the previous level of work fitness. In 30-50% of cases, the development
      of ischemic stroke and other forms of cerebrovascular insufficiency is caused by
      stenotic and occlusive lesion of aortic arch branches, being more frequently of
      atherosclerotic origin. Patients with brachiocephalic artery (BCA) lesion face an
      important problem of the origin and progression of different forms of cardiac
      rhythm disorders. In the presence of hemodynamically significant stenotic and
      occlusive lesion of brain vessels, even transient changes in cardiac rhythm may
      induce an additional deterioration of cerebral flow. In turn, the origin of
      arrhythmias in the immediate postoperative period in patients after
      reconstructions on the BCA is a serious complication which may lead to sudden
      death. The aim of the present study was to examine the long-term results of the
      surgical treatment in patients with associated BCA lesion and paroxysmal
      disorders of cardiac rhythm (PDCR). The treatment results were analyzed in 89
      patients aged 35 to 70 years. There were 66 (74.2%) men and 23 (25.8%) women. All
      the patients had undergone different BCA reconstructions. In the long-term
      period, this resulted in the lowering of the death rate. Besides, in the long
      term period, vascular reconstructions carried out in patients with associated BCA
      lesion and PDCR not only improved the neurologic status but also favoured the
      positive course of changes in arrhythmias in 36.4% of patients.

PMID- 14657918
TI  - [The diagnosis and surgical treatment of post-traumatic aneurysms of the
      brachiocephalic arteries].
AB  - This paper is concerned with the diagnostic technologies and the policy of
      surgical treatment of patients with traumatic injuries to the carotid arteries,
      which allowed to avoid fatal events and to attain optimal results in this severe
      patient group. The authors provide a detailed description of the procedure of
      spiral computed tomography with contrast examination of the arterial bed as well
      as of the technical aspects of operation with special reference to two patients.

PMID- 14657919
TI  - [Surgical management of elderly and senile patients with critical lower extremity
      ischemia].
AB  - This paper describes an experience with examination and surgical treatment of 194
      elderly (60-74 years); and senile (75 years and more) patients with critical
      lower extremity ischemia (CLEI) of atherosclerotic genesis. The patient group
      examined was marked by multiple coexistent pathology (primarily cardial)),
      appreciably increasing the risk of surgical intervention. The patients of both
      groups were provided altogether 345 operations. Because of remarkable concomitant
      pathology and compromised distal bed the greater part of patients underwent
      little traumatic non-reconstructive operations (56.5%); in many cases (41.3%),
      the necessary scope of intervention was divided into stages. On analysis of the
      results account was taken of the limited potential of performing in geriatric
      patients of prolonged operations as well as of the way of life of the
      overwhelming majority of old-group patients. The results were evaluated according
      to the scale suggested by the authors. The indicated treatment policy allowed to
      reach, the beneficial results in 80.1% of patients in the immediate period. In
      the long-term period (6 to 60 months), the positive results turned out stable in
      more than 70% of patients. This allows to recommend the approaches worked out for
      use in clinical practice for the treatment of geriatric patients presenting with
      CLEI.

PMID- 14657920
TI  - [Microsurgical transplantation of "lymph flaps"].
AB  - The review is concerned with the main historical stages in the development of
      "lymph flaps" transplantation. The author describes their blood supply, the
      topography of the constituent lymph structures, the feeding vascular pedicle,
      techniques of the harvesting, revascularization and restoration of lymph
      drainage. The review is intended for familiarization of a wide circle of
      physicians with the current strategy of microsurgical treatment of extremity
      lymphedema. This will allow to widen the outlook of practicing physicians and
      will give a possibility of further perfection of this trend.

PMID- 14657921
TI  - [Formation of a vascular access in patients with terminal chronic renal
      insufficiency for hemodialysis based on the new general theory of circulation].
AB  - Between 1993 and 2002, 41 operations were performed for formation of a vascular
      access (VA) to conduct hemodialysis using vascular transplants: autogenous veins
      (8 cases) and PTFE allografts (33 cases). Experience gained with the use of
      autogenous veins and PTFE allografts for creation of a permanent VA to carry out
      hemodialysis was summarized and analyzed. An attempt was made to explain the
      causes of thrombosis of autogenous veins transplanted and allo-vessels implanted
      on the basis of the new general theory of circulation. The technical procedures
      accomplished during operations aimed at the prolongation of the time of VA
      functioning were offered and substantiated.

PMID- 14657922
TI  - [Repair of infrarenal abdominal aorta in patient with aortic aneurysm and cava
      filter thrombosis].
AB  - The paper presents a case report on prosthetic correction of infrarenal abdominal
      aorta in aged patient with cava-filter thrombosis and lower limb post
      thrombophlebitis.

PMID- 14657923
TI  - [Surgical treatment of a patient over 90 years of age with abdominal aortic
      aneurysm].
AB  - Presented herein is a case of successful surgical treatment of infrarenal aortic
      aneurysm in a 95-year-old patient with coexistent pathology. The patient
      underwent replacement of the abdominal aorta with implantation of the inferior
      mesenteric artery. After treatment of complications which occurred in the
      postoperative period, the patient was discharged home in a satisfactory
      condition. The success of surgical treatment of infrarenal aortic aneurysm in
      elderly patients depends on the anesthesiological control and postoperative care
      of patients.

PMID- 14657924
TI  - [Vasaprostan in everyday practice of vascular surgery department].
AB  - The paper analyses vazaprostan administration to 88 patients with lower limb
      arteriosclerosis obliterans. Effectiveness of the drug is assessed in concordance
      with initial grade of ischemia.

PMID- 14657925
TI  - [On the etiology of abdominal aortic aneurysms: current state of the problem].
AB  - The paper reviews the last publications on the etiology and pathogenesis of
      abdominal aortic aneurysms (AAA), analyses different risk factors and possible
      pathological mechanisms related to the process of aortic aneurysmal dilatation.
      The authors conclude that AAA results from the combination of different factors
      whose special impact can vary in every case.

PMID- 14657926
TI  - [Anticoagulant therapy in reconstructive surgery of femoro-popliteo-tibial
      segment].
AB  - The paper compares the administration of low molecular weight heparins (LMWH) and
      previously used conventional heparin for arterial reconstructions of femoro
      popliteo-tibial segments. The data evidence of LMWH benefits for the given
      interventions. Authors review the latest publications devoted to this problem and
      analyze the potential and special features of simultaneous anticoagulant therapy
      and regional anesthesia.

PMID- 14657927
TI  - [Genetic engineering potential and perspectives in the management of critical
      ischemia].
AB  - The paper presents a new approach to management of lower limb critical ischemia
      which implements recent advances in molecular biology and genetic engineering
      technologies. A new original compound incorporating angiogenin gene was developed
      to activate neoangiogenesis processes after injection into living tissues.
      Experimental data evidence a potential efficacy of new method for complex
      management of critical ischemia.

PMID- 14657928
TI  - [Pathogenesis of atherosclerosis in patients with lipid metabolism disturbances:
      hypothesis on cholesterol utilization and atheromatous plaque formation].
AB  - Cholesterol is known to participate in atheromatous plaque formation coming from
      blood stream and affecting vascular endothelium in environment of elevated low
      density lipoproteins (LDL). Nevertheless, the occurrence of single atheromatous
      plaque evidences the possibility of local lipoprotein accumulation by vascular
      wall without systemic increase in serum LDLs. The author hypothesizes that in the
      absence of hypercholesterolemia atheroma can evolve through the utilization of
      modified LDL and free or etherified cholesterol, that remain in media non-removed
      by high density lipoproteins (HDL) owing to their structural damage after local
      vascular wall ischemia caused by vasa vasorum disorders. Disturbances in HDL
      acceptor function and transport of cholesterol and modified LDL to blood
      circulation and further into liver are followed by local accumulation of these
      products in smooth muscle cells. Overloaded by lipids smooth muscle cells move
      through internal fenestrated membrane thus activating receptor mechanism for
      transmission of modified lipoproteins to monocytes and capture of endothelial
      membrane and amorphous lipids by them in local lipid peroxidation area. A
      framework for hypothesis experimental and clinical testing is suggested.

PMID- 14657929
TI  - [Hemorheological changes at reconstructive operations on the aorta].
AB  - Fifteen patients who had undergone aortic reconstructions were examined.
      Hemorheologic studies were performed at the following stagest initial anesthesia,
      the end of operation, the early postoperative period, and the 2nd-3rd days after
      operation. A study was made of blood viscosity at a shift rate 5-300 s(-1), of
      suspension stability, caisson viscosity (CV), and the yield stress (YS). The back
      light diffusion intensity was recorded on the erythroaggregometer ADE=5 (Russia)
      to evaluate the time of linear aggregate formation (T(1)), the time of three
      dimensional aggregate formation (T(2)), characteristics of the end size of the
      aggregates (Ampl), total hydrodynamic strength of the aggregates (Beta), strength
      index of especially large aggregates (Ia((2,5))). The index of erythrocyte
      aggregation (IEA) and the index of erythrocyte deformation (IED) were also
      computed. Initially, the normal blood viscosity values were marked. However, in
      the early postoperative period, their values returned to the preoperative level.
      In patients with complications, blood viscosity appreciably rose, exceeding the
      preoperative parameters. At the end of operation there was a decrease in
      erythrocyte aggregation, especially due to the TT(1) and Ampl rise, while beta
      dropped. In the postoperative period, patients without complications demonstrated
      the growth of erythrocyte aggregation but Ampl of cell aggregation diminished. In
      the postoperative period, patients with complications showed a considerable
      intensification of erythrocyte aggregation due to the rise of Ampl, Beta and
      Ia((2,5)). Toward the end of operation a decrease of plasma viscosity was
      revealed in the presence of GV rise. In the postoperative period, patients with
      complications demonstrated the growth of plasma viscosity concurrently with CV
      lowering. Toward the end of operation the YS increased. However, in patients with
      the uncomplicated postoperative period, the magnitude of this parameter dropped
      and reached permissible values in the given patient group whereas in patients
      with complications, the YS remained significantly high.

PMID- 14657930
TI  - Endovascular rotary fragmentation in the treatment of massive pulmonary
      thromboembolism.
AB  - Endovascular rotary fragmentation using a modified pigtail catheter was provided
      to 20 patients with massive pulmonary thromboembolism. Fragmentation wes
      supplemented by the course of standard thrombolytic therapy (13 patients) or by
      the shortened treatment course (3 patients). Just after intervention the Miller
      index dropped on the average from 28.2+/-2,56 marks to 25.5+/-2.1 marks. Systolic
      pressure in the pulmonary artery increased on the average from 50.9+/-13.08 up to
      51.9+/-13.06 mm Hg, One female patient died 1.5 h after intervention because of
      cardiopulmonary insufficiency progression, 3-11 days after intervention (mean 6.3
      days) the patients underwent repeated cardiopulmonography. Within this period the
      Miller index constituted 16.7+/-4.3 marks on the average, systolic pressure in
      the pulmonary artery was equal to 33.8+/-9.45 mm Hg. Endovascular rotary
      fragmentation allows to reach swift recanalization of embolic occlusion and thus
      to gain a "gold hour" for thrombolysis. It improves the results of thrombolytic
      therapy and can become an original modality for the treatment of patients
      contraindicated thrombolysis.

PMID- 14657931
TI  - [Results of multimodality roentgenoradiologic examination of patients with
      initial cerebrovascular insufficiency].
AB  - Altogether 49 patients with the initial grade of cerebrovascular insufficiency
      were examined. The investigation was carried out using magnetic resonance
      tomography (MRT), magnetic resonance angiography (MRA) and single photon emission
      computed tomography (SPECT). In 39 (79.6%) cases, different lesions of the basic
      cerebral arteries, including mild atherosclerotic stenosis and kinking, were
      revealed. Analysis of the results of MRA showed that 9 (18.3%) patients had an
      abnormal structure of the circle of Willis. This should be taken into account
      while the hemodynamic importance of lesions of the cerebral arteries is
      estimated. 21 (142.8%) patients had craniovertebral dysplasia and 10 suffered
      from disturbances of venous circulation. Perfusion tomoscintigraphic examination
      discovered hypoperfusion of the brain tissue in all the cases and the lowered
      cerebrovascular reserve during the orthostatic test in 29 (59.1%) patients.
      CONCLUSION: all the above-indicated noninvasive tests proved to be reliable for
      assessment of brain circulation in the initial grade of cerebrovascular
      insufficiency and for decision and control of the treatment.

PMID- 14657932
TI  - [Some features of orthostatic venous hemodynamics of the lower extremities in
      healthy, subjects and patients with varicose disease according to duplex scanning
      data].
AB  - Duplex scanning of the subcutaneous, deep and perforating veins was performed to
      examine venous return and to establish the diagnosis of valvular venous
      insufficiency of the lower extremities in 32 clinically healthy subjects (64
      extremities) and 38 patients suffering from varicose disease (VD), when the
      patient was in the horizontal and vertical position. It has been established that
      in VD patients, the diameter of the deep and subcutaneous veins is greater than
      that in healthy subjects. When the patient is in the vertical position, the
      venous lumen expands 1.5-fold on the average (1.6-fold in healthy subjects and
      1.4-fold in VD patients) under the influence of orthoshtatic venous pressure
      (,the sum of hydrodynamic and hydrostatic pressure). The growth of the total
      venous pressure up to the design values in the distal segments of the lower
      extremities is removed not only by musculovenous pump (MVP) motion but also by
      the MVP of free standing (maintenance of body balance) as well as by the action
      of the arteriovenous pump (AVP). The frequency of recording the retrograde blood
      runoff at functional exerelse in healthy subjects when they are in the
      orthostatic position is dramatically reduced. This phenomenon may be related to
      the orthostatic dilatation of the great veins and tension of the cusps of the
      unchanged valves, which should be regarded as a functional component of the
      closing mechanism of the MVP, In YD patients when they are in the orthostatic
      position, the frequency of revealing the design valvular insufficiency (according
      to the duration of retrograde runoff) decreases in the deep and rises in the
      subcutaneous veins. Valvular insufficiency of the perforating veins of the leg
      was primarily recorded in the veins of Cockett. The data obtained indicate that
      examination of venous function of the lower extremities is desirable when the
      patients are in both horizontal and vertical position.

PMID- 14657933
TI  - [Tissue pressure in patients with phlebogenic edema].
AB  - This paper describes the results of tissue pressure measurement according to the
      Emmet technique in the subcutaneous fat at phlebogenic edema in 31 patients with
      lower extremity varicosity. The changes in the pressure were recorded over a
      length of 5-10 after needle impaction. The rate of tissue fluid resorption was
      measured. The indicators appeared normal in 16% of patients, absorption was
      accelerated in 39%, and deceleration of absorption was marked in 45% of patients.
      In the event of decelerated resorption, chronic edema was observed more
      frequently. The rate of saline resorption in health exceeded 4.8-fold the rate of
      tissue fluid absorption. In valvular insufficiency of the deep veins, this
      indicator is up to 4.8-fold as increased. Cessation of tissue fluid and/or saline
      resorption points to tissue swelling at the microcirculatory level. The given
      technique allows to diagnose latent edema, to objectively evaluate the patient
      tissue response to a specific drug and elastic appliance, to work out the well
      founded indications for phlebectomy, especially in young people. Also, it enables
      the assessment of the results of surgical intervention and making the early
      diagnosis of disease recurrences.

PMID- 14657934
TI  - [Microcirculation end effect of detralex in patients with chronic venous
      insufficiency of the lower extremities].
AB  - Fourteen patients with chronic venous insufficiency (CVI) of the lower
      extremities, class 0-4 according to the CEAP (1995) were examined for
      microcirculation (MC) and effect of detralex, using biomicroscopy of the
      conjunctival vessels and capillaroscopy of the nail matrix, with detailed
      computed morphometry. In 7 patients, CVI was associated with truncal arterial
      hypertension and in 5 with type 2 diabetes mellitus. It has been established that
      in CVI patients, there were remarkable disorders of MC and regional circulation.
      In addition to regression of the clinical manifestations of CVI, administration
      of detralex given in courses to 12 patients noticeably refined both regional
      circulation in the lower extremities and systemic MC, marked by abatement of
      perivascular edema, an increase in the number of the functioning microvessels and
      flow acceleration in them. Also, there was marked the lowering of intramuscular
      red blood cell aggregation.

PMID- 14657935
TI  - Lymphedema of the extremities: prospects of microsurgical treatment.
AB  - Presented herein is an experience with the treatment of 60 patients with
      lymphedema of the extremities, who had undergone transplantation of "lymphatic
      flaps". The treatment success is analyzed in both free microsurgical
      autotransplantation of tissue complexes (52 patients) containing intact lymphatic
      structures and in transposition (8 patients). The authors evaluate the potential
      of radio-nuclide diagnostic techniques for quantification of the effectiveness of
      surgical treatment. After transplantation and transposition of different types of
      "lymphatic flaps" good results were obtained in 36 (60%) patients. The prospects
      of the use of "lymphatic flaps" are assessed from the standpoint of the current
      concepts related to the surgical treatment of lymphedema of the extremities.

PMID- 14657936
TI  - What influences the standards of "quality" of carotid endarterectomy?
AB  - This paper analyzes the short-term results of 463 consecutive primary
      reconstructive operations on the carotid bifurcation based on the standards of
      "quality". In 383 (82.7%) cases, the patients were operated on for stenosis of
      the internal carotid artery (ICA); 60 (13%) patients had combination of stenosis
      and kingking of the ICA and 20 (4.3%) presented with isolated kinking of the ICA.
      Classic open carotid endarterectomy (CEAE) was performed in 240 cases, eversion
      CEAE in 144, resection with ICA redressment in 45, and ICA grafting in 28 cases.
      The perioperative lethality accounted for 1.54% (7 cases), per 463 operations,
      with the standard of "quality" being equal to 2%. Myocardial infarction was the
      cause of death in 5 cases, one patient developed homolateral stroke which
      eventuated in lethal outcome, and one more patient developed lethal stroke in the
      contralateral hemisphere. The incidence of homolateral strokes which did not
      eventuate in lethal outcome accounted for 1.94% (9 cases). The indicator "stroke
      plus lethality from stroke" in the general patient group was 2.38% which is even
      lower versus the standard of "quality" for asymptomatic patients and constitutes
      3%. Among asymptomatic patients proper, the indicator "stroke plus lethality from
      stroke" was equal to 0, among TIA patients to 0 at a 5% standard, and in patients
      with initial stroke, initial stroke, it amounted to 3.19% at a 7% standard.
      Perioperative strokes were not recorded in patients with ICA kingking or at ICA
      grafting. The basic factor of the risk of perioperative neurologic deficit was a
      history of stroke. Patients with different stages of cerebrovascular
      insufficiency did not significantly differ as regards age, sex distribution, the
      presence of CAD, arterial hypertension, diabetes mellitus, the degree of stenosis
      of the operated ICA and the time of its clamping at operation. Patients with a
      history of strokes differed significantly from the general group only in the
      incidence of lesion of the contralateral ICA and in the frequency of the use of
      internal shunt. Analysis of the risk factors of perioperative stroke in patients
      with a history of strokes has shown that they were diabetes mellitus and the use
      of internal shunt. The development of perioperative stroke among patients with a
      history of stroke was not influenced by the incidence of contralateral ICA
      lesion, the standing of cerebral circulatory distress or the size of an ischemic
      focus. The initial character of ICA lesion and the type of reconstruction did not
      affect the origin of perioperative focal deficits or lethality.

PMID- 14657937
TI  - Surgical strategy for combined wounds of vessels and internal organs.
AB  - Surgical strategy and outcomes were analysed for 51 patients with combined wounds
      of internal organs and major blood vessels, with total 87 organ and 65 vessel
      injures. In 29 cases intracavity vessels were injured, in 22 - peripheral ones.
      In 47 cases (92.1%) traumas were gunshot. On admission 43 patients were in poor
      clinical condition with III-IV grade shock. The delay of surgical intervention
      did not exceed 30-40 min, all patients were operated in emergency, regardless of
      complete preoperative preparation. Blood reinfusion was used for all intracavity
      bleedings. The consequence of surgical steps was determined by localization of
      vascular trauma, bleeding intensity and severity of organ injuries. In order to
      decrease invasiveness and duration of surgery, conventional wound suturing was
      used for 53 organs, vascular plasty and sutures - in 35 cases, ligation of
      vessels - in 27. Lobectomy was executed in 1 case, intestinal resection and
      anastomosis - in 8, ileo-and colostomy - in 7 patients. Total 73 internal organs
      and 62 vessels were reconstructed. Postoperative complications have developed in
      30 patients (58.8%), lethal outcome occurred in 3 patients during operation and
      in 10 (25.4%) - postoperatively. The majority of complications and deaths were
      observed for thoracoabdominal traumas. High postoperative mortality was also seen
      for patients with combined injuries of abdominal organs and vessels (13.7%).

PMID- 14657938
TI  - [Extra-anatomic bypass as a method of choice for surgical correction of
      iliofemoral lesions in elderly patients].
AB  - From fall 1994 to December, 2000, total 73 reconstructions of iliofemoral lesions
      (predominately of atherosclerotic origin) were fulfilled in 70 elderly patients.
      Long-term outcomes (to 5 years of follow-up) of iliofemoral surgical
      interventions for 2B-4 grade lower limb ischemia were assessed. The first group
      (mean age 74.5) included patients with extra-anatomic reconstructions (31),
      control group (mean age 70.1) comprised "direct" iliofemoral bypass (42
      procedures). Intervention extend was determined by diagnostic data (Doppler
      ultrasonography, duplex scanning, angiography) and severity of concomitant
      pathology. Elderly cohort of patients is especially vulnerable to multilevel
      atherosclerotic lesions, thus practically in all cases distal anastomosis was
      formed with deep femoral artery eliminating its stenosis. Cumulative rate of
      fatal outcome toward the end of 2000 in the first group was somewhat higher then
      in control. Causes of deaths in the first group were characterized by greater
      variety, while in control one half of deaths was related to acute coronary
      insufficiency. In survivors of the first group recurrent lower limb ischemia
      occurred in 3 cases, in 2 of them resulting in amputation. In control lower limb
      ischemia relapsed in 6 patients with subsequent limb amputation in 4 of them for
      thrombosis of iliofemoral bypass. Toward the end of 2000 patent grafts numbered
      54.2% in the first group and 71.9% in control, rate of limb salvage - 87.5% and
      82.5%, respectively. High risk of lethal outcome in elderly patients with
      multifocal atherosclerotic lesions and severe comorbidities during standard
      iliofemoral reconstructions permit to consider extra-anatomic bypass as one of
      possible surgical solutions, that enables to achieve good clinical and functional
      results, to save a limb without expansion of procedure invasiveness.

PMID- 14657939
TI  - [Femoro-popliteal reocclusion. Obligatory reoperation?].
AB  - The paper presents 408 cases of femoro-poptiteal reocclusion. The effectiveness
      of 202 reoperations is analyzed. Authors give definition of repeated operations
      and restitution of secondary patency in femoro-popliteal segment. Repeated
      operation is a special entity differing from initial one and including graft
      exchange, occasionally of the same construction. Secondary patency is a
      restitution of blood flow without graft or operation type exchange. Effectiveness
      of reoperations appeared to depend on initial intervention type, timing and grade
      of lower limb ischemia. The analysis of this correlation served the basis for
      development of reoperation indications, decision algorithm for reoperation type,
      timing and graft material. The validity and effectiveness of second or further
      reoperations are reviewed. The relation of limb salvage rate in femoro-popliteal
      reocclusions and both surgical and conservative management strategies is driven.

PMID- 14657940
TI  - [Prevention and prognosis of cardiac complications in patients following
      reconstruction of terminal aorta or lower limb arteries for atherosclerotic
      lesions].
AB  - The paper analyses several risk factors of cardiac postoperative complications in
      284 patients with atherosclerosis of terminal aorta or lower limb arteries and
      correlation between preoperative management and intervention outcomes. Results of
      preoperative functional examination (transesophageal electric stimulation,
      echocardiography) and intraoperative monitoring of central hemodynamics were
      highly prognostic for cardiac complications. Causative analysis of cardiac
      complications enabled to develop a preventive strategy that has decreased the
      complication rate in 1.8 times.

PMID- 14657941
TI  - [Long-term outcomes of balloon angioplasty for aortic coarctation].
AB  - From 1994 to 2001 balloon angioplasty was fulfilled for 19 patients aged from 4
      to 28 (mean 11.0+/-7.0) with discrete type aortic coarctation. Early outcomes
      were satisfactory in all cases. Catheterization showed 10 mm Hg decrease in
      systolic pressure gradient (SPG). Long-term results (from 6 months to 8 years,
      mean 3.0+/-2.5) were evaluated with transthoracic EchoCG, Doppler ultrasound,
      duplex scanning of iliofemoral segment and CT-angiography with 3D reconstruction.
      Surgical outcomes were considered good when SPG did not exceed 20 mm Hg for
      Doppler ultrasound and 25 mm Hg for Doppler EchoCG. In the study group there was
      statistically significant decrease in arterial pressure in right upper limb and
      SPG (measured with both Doppler EchoCG and Doppler ultrasonography) and rise of
      ankle-brachial index. Beneficial hemodynamic effect was detected in 15 from 19
      patients (79%). Recoarctation has developed in 4 (21%) patients, in 1 (5.3%) case
      it was combined with true posttraumatic aortic aneurysm. Three patients underwent
      open surgical intervention with uneventful postoperative period. Aneurysmal
      dilatation of thoracic aorta has developed in 1 patient (5.3%), non-progressive
      intimal dissection - in another one (5.3%), 2 patients (10.5%) experienced
      ipsilateral 40-60% stenosis of right external iliac and femoral arteries. Thus
      good long-term outcomes of balloon angioplasty in patients with discrete type
      aortic coarctation were achieved in 79% cases. Patients after balloon angioplasty
      must be assessed regularly with non-invasive diagnostic methods such as Doppler
      ultrasonography, Doppler EchoCG, CT-angiography.

PMID- 14657942
TI  - [Endovascular treatment of subclavian arterial aneurysm using stent graft].
AB  - The authors describe a clinical case of successful endovascular treatment of
      subclavian arterial pseudoaneurysm using the stent graft JOSTENT-GRAFT 48 mm in
      length and 6 mm in diameter in a 49-year-old patient. The aneurysm developed over
      a length of 2 years as a result of polytrauma without remarkable circulatory
      disorders in the distal arterial bed of the upper extremity. Further existence of
      aneurysm was conjugated with a risk of ischemic or neurologic complications. This
      observation demonstrates the current potential of roentgenoendovascular surgery
      allowing to successfully replace the technically difficult and traumatic surgical
      intervention in the event of formation of pseudoaneurysms by the pulsatory
      hematoma type.

PMID- 14657943
TI  - [Successful treatment of a patient with internal carotid aneurysm].
AB  - Presented herein is a clinical report of the surgical treatment of a female
      patient with left internal carotid aneurysm. Patient M, aged 58 years was
      hospitalized to the Department of Vascular Surgery, RSCS RAMS, with complaints of
      a pulsatile formation in the area of the neck on the left, persistent headaches,
      frequently occurring dizziness, and multiple episodes of loss of consciousness.
      The patient has been ailing for 20 years. Examination discovered a rounded
      pulsatile formation about 3 cm in diameter in the left lateral area of the neck
      in the internal carotid projection. Duplex scanning revealed aneurysm of the left
      internal carotid artery measuring 2,3 cm x 3.8 cm. Computerized tomography
      confirmed aneurysm of the left internal carotid artery. On December 10, 2002 the
      patient underwent resection of aneurysm of the left internal carotid artery
      followed by establishment of an end-to-end anastomosis. The immediate
      postoperative period was uneventful. The patient was discharged home in a
      satisfactory condition.

PMID- 14657944
TI  - Primary aortoduodenal fistula: successful grafting with axillo-bifemoral bypass.
AB  - Primary aortoduodenal fistula (PADF) is uncommon direct pathological
      communication between the abdominal aorta and duodenum, which may cause life
      threatening gastrointestinal bleeding. PADF leads to high mortality and morbidity
      unless it is promptly evaluated and appropriate surgical intervention performed.
      We present a case report describing PADF treated successfully with
      axillobifemoral bypass. A 70-year-old male was admitted in our hospital with
      severe back and abdominal pain. A pulsative tumor mass was palpated in the middle
      abdomen. Previous ultrasonography had shown abdominal aortic aneurysm. There were
      no symptoms of active gastrointestinal bleeding, but the patient had moderate
      anaemia. Computer tomography revealed infrarenal abdominal aortic aneurysm.
      Intraoperatively, PADF was diagnosed. The duodenum was repaired and the abdominal
      aorta was closed directly below the renal arteries. At the next stage, extra
      anatomic grafting was performed, because frank pus was found in the abdominal
      cavity. By present time, the axillobifemoral bypass has been patent for 2 years.

PMID- 14657945
TI  - [Roentgenendovascular arrest of bleeding in iatrogenic injury to the subclavian
      artery].
AB  - The authors present a clinical case report concerned with the arrest of
      continuous external bleeding from the subclavian artery due to its iatrogenic
      injury at transluminal endoprosthetics by stent graft. In patient Zh. aged 23
      years, the subclavian artery was injured when an attempt was made to piece a
      subclavian venous catheter. Under conditions of remarkable coagulopathy because
      of prolonged mechanical jaundice, the patient developed a major hematoma of the
      right neck and the right chest. To handle continuous bleeding, a JOSTEHT-GRAFT
      (7.0 in D, 28 mm in length) was implanted into subclavian artery defect. The
      bleeding was handled and the patency of the great artery was maintained. The
      roentgenendovascular procedure allowed to avoid a technically difficult traumatic
      surgical intervention under conditions of pronounced anemia and coagulopathy.

PMID- 14657946
TI  - Caspase-3 activation in systemic anaplastic large-cell lymphoma.
AB  - Anaplastic large-cell lymphoma (ALCL), as currently defined, includes a subset of
      tumors that have abnormalities of chromosome 2p23 (alk gene) resulting in
      overexpression of anaplastic lymphoma kinase (ALK). We have previously shown
      differences in apoptotic rate and expression of apoptosis-related proteins
      between ALK-positive and ALK-negative ALCL. In this study, we assessed for
      activated caspase-3 (aC-3), an executioner of apoptotic cell death, in ALCL cell
      lines and tumors. We used the Karpas 299 and SU-DHL-1 cell lines, and the caspase
      inhibitors Boc-D-FMK and DEVD-FMK to investigate the role of caspase-3 activation
      in tumor cell death after treatment with doxorubicin. Cell viability and
      apoptosis were assessed by trypan blue and Annexin-V methods. A caspase-3 assay
      was used to evaluate caspase-3 enzymatic activity. Caspase-3 activity was
      significantly increased in Karpas-299 and SU-DHL-1 cells treated with
      doxorubicin, but remained as low as control levels with addition of Boc-D-FMK or
      DEVD-FMK. Expression of aC-3 was also assessed immunohistochemically in 57 ALCL
      tumors. The mean percentage of aC-3 positive tumor cells was 3.2% in ALK-positive
      ALCL compared with 1.2% in ALK-negative ALCL (P=0.0003, Mann-Whitney test), and
      inversely correlated with BCL-2 expression (P=0.01, Mann-Whitney test). aC-3
      expression did not correlate with patient outcome in either the ALK-positive or
      ALK-negative ALCL groups. In conclusion, doxorubicin-induced cell death of ALK
      positive ALCL cells involves caspase-3 activation in vitro. aC-3 levels correlate
      with ALK expression in ALCL tumors.

PMID- 14657947
TI  - hASH1 expression is closely correlated with endocrine phenotype and
      differentiation extent in pulmonary neuroendocrine tumors.
AB  - The human homolog 1 of the Drosophila neurogenic achaete-scute genes, hASH1, is
      specifically expressed in fetal pulmonary neuroendocrine cells and in some
      neuroendocrine tumor cell lines. However, no data have been gathered regarding
      its in vivo expression in tumors. hASH1 mRNA expression was investigated by in
      situ hybridization in 238 surgically resected lung carcinomas, and the
      correlations between hASH1 expression status and immunostaining results of
      neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin
      releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1
      expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical
      carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell
      neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively,
      but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The
      2 hASH1+ adenocarcinomas also expressed multiple neuroendocrine markers. Thus,
      hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes.
      However, not all neuroendocrine tumors expressed hASH1. Within the entities of
      large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression
      correlated very closely with chromogranin A, gastrin-releasing peptide and
      calcitonin expression (P<0.0001, r=0.852), but was not related to neural cell
      adhesion molecule expression (P=0.8892), suggesting that hASH1 expression, at
      least in lung cancer, is associated with endocrine phenotype expression other
      than 'neuroendocrine differentiation' in a broad sense. The fact that hASH1 was
      virtually absent in almost fully differentiated typical carcinoids, but was
      expressed in most, if not all, less differentiated atypical carcinoids as well as
      large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that
      hASH1 expression in lung cancer imitates its early and transient expression in
      fetal development, and that hASH1 is instrumental in the establishment, but not
      in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression
      correlated with a significantly shortened survival in small-cell carcinoma
      patients (P=0.041).

PMID- 14657948
TI  - Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype.
AB  - Extraskeletal myxoid chondrosarcoma is a rare mesenchymal soft-tissue malignancy
      of putative chondrocytic differentiation. Occasional overt cartilage formation,
      positivity for S-100 protein, and ultrastructural analysis have supported this
      view. However, most extraskeletal myxoid chondrosarcomas do not show chondroid
      tissue formation, and S-100 protein is found much less commonly than has been
      reported. Both these observations cast doubt on the histogenetic classification
      of extraskeletal myxoid chondrosarcoma as a chondroblastic entity. Mostly using
      matrix proteins as markers of mesenchymal cell differentiation, we investigated
      the biochemical matrix composition and cellular phenotype of the tumor cells in
      representative specimens from 14 extraskeletal myxoid chondrosarcomas. In all but
      one tumor specimen, which showed histomorphologically overt cartilage formation,
      only occasional staining for the proteoglycan aggrecan was found. Specimens from
      two tumors showed presence of collagen type II, and none was positive for
      collagen type X. Instead, collagen types I, III, and VI were diffusely positive.
      Also, S-100 protein was largely absent. Our results suggest that the basic
      cellular phenotype of extraskeletal myxoid chondrosarcoma is not chondrocytic or
      prechondrocytic and that extraskeletal myxoid chondrosarcoma is not a
      chondrosarcomatous entity. Extraskeletal myxoid chondrosarcoma consists most
      likely of primitive mesenchymal cells with focal, multidirectional
      differentiation. Chondrocytic differentiation is an unusual facet in the spectrum
      of differentiation patterns exhibited by these lesions.

PMID- 14657949
TI  - Topographical distribution of allelic loss in individual lung adenocarcinomas
      with lymph node metastases.
AB  - Adenocarcinomas of the lung are characterized by morphological heterogeneity, and
      since carcinogenesis has been suggested to be a multistep process involving
      sequential accumulation of multiple genetic alterations, the morphological
      heterogeneity may represent a cross-sectional view of genetic alterations within
      individual tumors. Therefore, to elucidate whether, and which, genetic
      alterations accumulated in relation to morphological cancer progression, we
      examined 56 microdissected sites for topographical distribution of loss of
      heterozygosity (LOH) in 12 adenocarcinomas of the lung with bronchioloalveolar
      (BA) and invasive components in their primary tumors and metastases to lymph
      nodes. The morphological changes from noninvasive BA lesions to invasive and
      metastatic components were characterized by a significant rise in the prevalence
      of allelic losses (P<0.05). Individually, eight cases (67%) showed accumulation
      of genetic alterations from BA lesions to metastases. LOHs in multiple foci in
      one case were compared to determine whether they were shared at all tumor sites
      as an early event or localized in metastases as an additional event. LOHs at 5q
      and 17p may be crucial steps in the early phase of development to metastasis,
      while 18q loss may be an additional step. These findings suggested that the
      cancer cells in some pulmonary adenocarcinomas evolved from the BA lesions to the
      invasive and metastatic lesions.

PMID- 14657950
TI  - Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in
      colorectal cancer.
AB  - Endoglin (CD105) has been shown to be a more useful marker to identify
      proliferating endothelium involved in tumor angiogenesis than panendothelial
      markers such as CD31. We investigated endoglin and vascular endothelial growth
      factor expression as possible prognostic markers in colorectal cancer. Surgical
      specimens from 150 patients with resected colorectal carcinomas were
      immunostained for endoglin, CD31 and vascular endothelial growth factor.
      Colorectal carcinoma cases consisted of 50 cases without lymph node metastases,
      50 cases with only lymph node metastases and 50 cases with liver metastases (38
      cases also had positive lymph nodes). Positively stained microvessels were
      counted in densely vascular foci (hot spots) at x 400 fields in each specimen.
      For vascular endothelial growth factor, intensity of staining was scored on a
      three-tiered scale. Results were correlated with other prognostic parameters.
      Endoglin demonstrated significantly more proliferating neoplastic microvessels
      than CD31 (31+/-10 vs 19+/-8/0.15 mm2 field, P<0.001). Low vascular endothelial
      growth factor expression within tumor cells was seen in 49 (33%) and high
      expression in 101 cases (67%). There was a positive correlation of endoglin, CD31
      counts and vascular endothelial growth factor overexpression with the presence of
      angiolymphatic invasion and lymph node metastases (P<0.05). Only endoglin counts
      correlated significantly with liver metastases and positive vascular pedicle
      lymph nodes (P<0.05), while vascular endothelial growth factor showed significant
      correlation with the depth of invasion (P<0.01). Endoglin, by staining higher
      numbers of the proliferating vessels in colon carcinoma, is a more specific and
      sensitive marker for tumor angiogenesis than the commonly used panendothelial
      markers. Endoglin staining also showed prognostic significance with positive
      correlation with angiolymphatic invasion and metastases to lymph nodes and liver.

PMID- 14657951
TI  - Acute rejection and graft survival in renal transplanted patients with viral
      diseases.
AB  - Transplanted patients are susceptible to viral infections; thus, the aim of this
      study was to evaluate the features of acute rejections and the outcome of the
      renal graft in transplanted patients with herpes virus diseases. Renal biopsies
      from 30 renal transplanted patients undergoing early acute rejection (type IA and
      IB according to the Banff 97 classification) were evaluated. In total, 15 of
      these patients experienced cytomegalovirus (CMV) or Epstein-Barr virus disease
      within the first year following transplantation (group I) and 15 patients showed
      no evidence of viral infection (group II). No significant differences between the
      groups in terms of age, male/female ratio, living/cadaveric donor ratio, cold
      ischemia time, HLA A-B matching, pretransplant panel reactive antibody test,
      occurrence of post-transplant tubular necrosis, plasma levels of cyclosporin A
      and mean percent increase of serum creatinine at the time of the biopsy were
      observed. In group I biopsies, the mean number of interstitial plasma cells, as
      well as the mean number of CD79a-positive cells (B lymphocytes and plasma cells)
      was significantly higher than in group II (P<0.01 and <0.01, respectively). There
      was a positive correlation between the number of infections and the number of
      plasma cells (P<0.05). In transplanted patients, CMV can trigger the formation of
      anti-endothelial cell antibodies, which have been proposed to play a role in
      antibody-mediated rejections. We investigated whether a deposition of C4d, a
      marker of antibody-mediated reactions, was present in renal peritubular
      capillaries. In group I C4d deposition was found in five cases, while in group II
      it was not observed (P<0.05). In group I, 7/15 patients developed chronic
      allograft nephropathy vs 1/15 patients in group II (P<0.05). The estimated 1-, 5-
      and 8-year cumulative graft survival rates were 80, 66 and 57%, respectively, in
      group I, while in group II the estimated 8-year cumulative survival rate was 100%
      (P<0.05). In conclusion, acute rejection biopsies of patients with viral
      infections displayed plasma cell infiltrates and, in several cases, C4d
      deposition. Our study suggests a role of B lymphocytes in the pathology of these
      rejections and confirms the association between viral infections and poor graft
      survival.

PMID- 14657952
TI  - Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic
      immunohistochemical analysis of 188 cases.
AB  - MUC1 (epithelial membrane antigen) is a membrane-associated mucin known to
      interfere with both cell-cell and cell-matrix adhesions. Overexpression has been
      associated with poor prognosis in a variety of cancers. We investigated the
      expression of MUC1 (using two different antibodies, MA695 and E29) and E-cadherin
      in renal cell carcinomas (137 conventional, 23 chromophobe, 20 papillary, and
      eight unclassified tumors) with respect to diagnostic and prognostic significance
      using a tissue microarray technique. Immunoreactivity was correlated with
      histological subtype, pT-stage, and grade using the chi2 test or the Fisher's
      exact test, respectively. Impact on disease-free survival was analyzed using the
      Kaplan-Meier method and the log-rank test. Immunoreactivity of more than 10% of
      cancer cells with MA695, E 29, and E-cadherin antibodies was found in 112/133
      (84%), 86/133 (65%), and 7/131 (5%) conventional, 20/22 (91%), 19/22 (86%), and
      21/22 (95%) chromophobe, 13/20 (65%), 8/20 (40%), and 3/20 (15%) papillary as
      well as 5/8 (63%), 5/8 (63%), and 4/8 (50%) unclassified carcinomas,
      respectively. The two different MUC1 antibodies yielded comparable staining
      results. A diffuse cytoplasmic staining pattern for MUC1 was found exclusively in
      chromophobe carcinomas, whereas conventional and papillary subtypes showed
      predominantly membranous staining (P<0.0001). Regarding papillary carcinomas,
      MUC1 was predominantly associated with type 1 (P=0.0001), and E-cadherin with
      type 2 (P=0.049) tumors. The cellular staining pattern of MUC1 in conventional
      tumors was related to pT-stage (P=0.002) and tumor grade (P=0.001): Low-stage
      (pT1/pT2) and grade (G1/G2) tumors showed a predominantly apical membranous
      staining, high-stage (pT3a/pT3b) and grade (G3/G4) tumors a predominantly
      circumferential membranous staining (with or without additional diffuse
      cytoplasmic immunoreactivity), which, in the conventional subtype, was associated
      with poor prognosis (P<0.0001). In conclusion, MUC1 and E-cadherin are
      diagnostically and prognostically useful markers in renal tumor pathology,
      especially when cellular staining patterns are considered.

PMID- 14657953
TI  - Recommendations for the reporting of lymphoid neoplasms: a report from the
      Association of Directors of Anatomic and Surgical Pathology.
AB  - In this report, the Association of Directors of Anatomic and Surgical Pathology
      (ADASP) provides guidelines for the reporting of lymphoid neoplasms. The World
      Health Organization Classification of Tumors of the Haematopoietic and Lymphoid
      Tissues is the preferred international standard for diagnostic criteria (disease
      definition) and nomenclature. Ancillary studies are often required, and the
      Association recommends that immunophenotypic and genotypic information be
      integrated into the final report, to the extent possible.

PMID- 14657955
TI  - TaqMan RT-PCR assay coupled with capillary electrophoresis for quantification and
      identification of bcr-abl transcript type.
AB  - Chronic myelogenous leukemia is characterized by the presence of the reciprocal
      t(9;22)(q34;q11) in which c-abl located on chromosome 9, and the bcr locus
      located on chromosome 22, are disrupted and translocated creating a novel bcr-abl
      fusion gene residing on the derivative chromosome 22. In most cases, the
      breakpoint in abl occurs within intron 1. Depending on the breakpoint in bcr,
      exon 2 of abl (a2) joins with exons 1 (e1), 13 (b2), or 14 (b3), or rarely to
      exon 19 (e19) of bcr resulting in chimeric proteins of p190, p210 and p230,
      respectively. Currently, several multiplex real-time reverse transcriptase
      polymerase chain reaction (RT-PCR)-based assays for detecting bcr-abl are
      available to assess the levels of the three common fusion transcripts, b2a2, b3a2
      and e1a2. Although these assays circumvent the requirement for individual fusion
      sequence quantitative polymerase chain reaction-based assays, they do not
      identify the specific fusion transcript. Knowledge of the latter is useful to
      rule out false-positive results and to compare clones before and after therapy.
      We designed a novel multiplex real-time RT-PCR assay to detect bcr-abl that
      allows accurate quantification and determination of the specific fusion
      transcript. In this assay, abl primer labeled at its 5' end with the fluorescent
      dye NED (Applied Biosystems) is incorporated into the bcr-abl fusion product
      during amplification. The NED fluorescent dye in abl primer, without interfering
      with fluorescent TaqMan probe signal, allows subsequent identification of the
      fusion transcript by semiautomated high-resolution capillary electrophoresis and
      GeneScan analysis.

PMID- 14657954
TI  - Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma
      and lung adenocarcinoma.
AB  - The distinction between pleural malignant mesothelioma and pleural infiltration
      by adenocarcinomas has complex therapeutic and medicolegal implications. Although
      the panel of adenocarcinoma-associated antibodies and one or two mesothelioma
      markers is useful in this purpose, most of these antibodies are not totally
      specific. We determined the diagnostic value of MUC4 immunostaining in this
      issue. MUC4 gene expression was also studied by in situ hybridization and RT-PCR.
      MUC4 is a membrane-bound mucin that has been suggested to be implicated in
      malignant progression in humans and rats. The MUC4 gene is expressed in various
      normal epithelial tissues of endodermic origin and carcinomas. In the respiratory
      tract, MUC4 transcripts have been detected in normal respiratory epithelium and
      lung carcinomas. MUC4 protein was expressed in 32 of 35 (91.4%) lung
      adenocarcinomas on paraffin-embedded tissue. None of the 41 malignant
      mesotheliomas nor the 32 cases of benign mesothelial cells expressed MUC4 at the
      protein and mRNA levels. We conclude that MUC4 is a very specific (100%) and
      sensitive (91.4%) marker of lung adenocarcinomas on paraffin-embedded tissue that
      could be useful in diagnostic practice in the distinction between malignant
      mesothelioma and adenocarcinoma.

PMID- 14657956
TI  - Comparative genomic hybridization study of placental site trophoblastic tumour: a
      report of four cases.
AB  - Placental site trophoblastic tumour (PSTT) is a neoplastic proliferation of the
      implantation intermediate trophoblast. Although clinicopathological studies are
      not uncommon in case reports or small series, molecular and genetic studies are
      quite limited. Four archived cases of PSTT were successfully analysed by
      comparative genomic hybridization (CGH) in this study. Regional chromosomal gains
      were observed in two cases. One case showed chromosomal gains in the regions of
      19p13.2, 21q11-21 and 22q12. The second case demonstrated a single regional
      chromosomal gain involving 21q21. No chromosomal loss is observed. The remaining
      two cases showed a balanced CGH profile without detectable chromosomal gain or
      loss. In summary, although chromosomal alterations detectable by CGH are not
      common, rare chromosomal gains do occur in PSTT. The recurrent chromosomal gain
      involving chromosomal 21q observed in two of our cases deserves additional
      studies to ascertain whether it carries any pathobiological significance.

PMID- 14657957
TI  - Histological margin assessment for breast ductal carcinoma in situ: precision and
      implications.
AB  - Local recurrence after lumpectomy for ductal carcinoma in situ (DCIS) is a major
      concern and is related to residual disease in the breast. We studied the
      predictive value of lumpectomy margins for residual DCIS and compared our results
      and pathological processing techniques with those published in the literature.
      Margin status was determined for 89 patients with screen-detected DCIS who had
      lumpectomy and re-excision, for the presence and extent of residual disease.
      Margin width was defined as the narrowest distance between tumor and any inked
      margin or, where margins were positive, classified into focal involvement (<1 mm
      of the inked surface involved), minimal (>or=1<15 mm) and extensive (>or=15 mm).
      The amount of residual tumor was quantified according to the number of ducts
      involved with tumor: small (fewer than 10 ducts) or large (10 or more ducts)
      residuum. The initial margin status was a significant predictor for the presence
      of residual tumor in re-excision specimens (P=0.006). There was residual tumor in
      44 and 45% of close non-involved (>1 and <or=1 mm width) margins, 67% of focally,
      71% of moderately and 94% of extensively positive margins. The pathologic tumor
      size was also a predictor for the presence of residual tumor with 27, 68 and 74%
      of lesions measuring <or=10, 11-25, >25 mm,respectively, showing residual
      disease. The presence of residual tumor was not significantly related to age,
      mammographic appearance, nuclear grade or intraductal necrosis. The initial
      margin status was found to predict for the amount of residual tumor. With careful
      margin assessment, margin status after lumpectomy for DCIS can be used to predict
      for the presence and amount of residual tumor in the breast and is a guide to
      further management decisions. A standard for margin status reporting and
      pathological processing of screen-detected DCIS in situ lesions will help in the
      interpretation of data from different institutions.

PMID- 14657958
TI  - Hypermethylation of the hMLH1 promoter with absent hMLH1 expression in medullary
      type poorly differentiated colorectal adenocarcinoma in the elderly.
AB  - To clarify the significance of hMLH1 promoter hypermethylation in the development
      of medullary-type poorly differentiated colorectal adenocarcinoma, we studied the
      status of promoter methylation and hMLH1 expression in 23 medullary-type and 12
      pleomorphic-type carcinomas, as well as the pathology and microsatellite status.
      In medullary-type carcinomas, the percentages of cases with promoter methylation
      (83%) and an absence of hMLH1 expression (91%) were significantly higher than in
      pleomorphic-type carcinomas (14 and 17%), respectively. The rate of
      microsatellite instability in the medullary type was significantly higher than
      that of the pleomorphic type (87 vs 40%, P<0.01). Compared with pleomorphic-type
      carcinomas, medullary-type carcinomas were significantly associated with hMLH1
      promoter methylation, absent expression of hMLH1 protein, microsatellite
      instability, as well as a proximal location, a Crohn's-like lymphoid reaction, a
      low incidence of lymph node metastasis, and a favorable outcome. Medullary-type
      carcinomas accumulated with advancing age, especially in the female. These
      results indicated that hMLH1 hypermethylation, concurrent with a lack of its
      protein expression, may play an important role in the development of medullary
      type poorly differentiated colorectal adenocarcinomas in the elderly.

PMID- 14657959
TI  - Intrapulmonary airways visualized by staining and clearing of whole-lung
      sections: the transparent human lung.
AB  - Methods for the study of cartilaginous airways represent technically very
      laborious and time-consuming procedures, many of these with the inevitable
      disruption or elimination of the distal bronchi and bronchioles. We describe and
      illustrate a methodology to demonstrate the cartilaginous support of the most
      distal intrapulmonary airways in hemisections or slabs of whole-, fixed-lung
      specimens. By this process, the cartilaginous framework of intrapulmonary air
      passages is highlighted and their outlines are defined. An important and distinct
      benefit of our procedure is the preservation of the alveolar parenchyma,
      vasculature and pleura, serving as an anatomic structural context. This improved
      methodology is based on procedures used in the past, now applied to entire half
      sections or slabs of lungs, stained with toluidine blue, subsequent removal of
      stain from noncartilaginous elements and finally clearing of the specimen. The
      procedure takes 7-8 days but with limited technical - manual involvement. The
      resulting specimens demonstrate a highly complex, variable and at times, even
      unpredictable distribution of cartilage throughout the bronchial anatomy. This
      method represents a practical way of studying intact, this vital component of the
      respiratory tract. It also allows assessment of the potential implication of
      these critical smaller pathways in pathologic conditions, where thus far they
      have been under-studied.

PMID- 14657960
TI  - Induction of apoptosis and stress response in ovarian carcinoma cell lines
      treated with ST1926, an atypical retinoid.
AB  - To understand the molecular mechanisms mediating apoptosis induction by a novel
      atypical retinoid, ST1926, the cellular response to drug treatment was
      investigated in IGROV-1 ovarian carcinoma cells carrying wild-type p53 and a
      cisplatin-resistant p53 mutant subline (IGROV-1/Pt1). Despite a similar extent of
      drug-induced DNA strand breaks, the level of apoptosis was substantially higher
      in p53 wild-type cells. p53 activation and early upregulation of p53-target genes
      were consistent with p53-dependent apoptosis in IGROV-1 cells. Stress-activated
      protein kinases were activated in both cell lines in response to ST1926. This
      event and activation of AP-1 were more pronounced in IGROV-1/Pt1 cells, in which
      the modulation of DNA repair-associated genes suggests an increased ability to
      repair DNA damage. Inhibition of JNK or p38 stimulated ST1926-induced apoptosis
      only in IGROV-1 cells, whereas inhibition of ERKs enhanced apoptosis in both the
      cell lines. Such a pattern of cellular response and modulation of genes
      implicated in DNA damage response supports that the genotoxic stress is a
      critical event mediating drug-induced apoptosis. The results are consistent with
      apoptosis induction through p53-dependent and -independent pathways, regulated by
      MAP kinases, which likely play a protective role.

PMID- 14657961
TI  - Requirement of caspase-mediated cleavage of c-Abl during stress-induced
      apoptosis.
AB  - c-Abl protein tyrosine kinase plays an important role in cell cycle control and
      apoptosis. Furthermore, induction of apoptosis correlates with the activation of
      c-Abl. Here, we demonstrate the cleavage of c-Abl by caspases during apoptosis.
      Caspases separate c-Abl into functional domains including a Src-kinase, a
      fragment containing nuclear import sequences, a fragment with an actin-binding
      domain and nuclear export sequence. Caspase cleavage increases the kinase
      activity of c-Abl as demonstrated by in vitro kinase assays as well as by auto-
      and substrate phosphorylation. Cells in which c-Abl expression was knocked down
      by RNA interference resisted cisplatin- but not TNFalpha-induced apoptosis. A
      similar selective resistance against cisplatin-induced apoptosis was observed
      when cleavage resistant c-Abl was overexpressed in treated cells. Our data
      suggest the selective requirement of c-Abl cleavage by caspases for stress
      induced, but not for TNFalpha-induced apoptosis.

PMID- 14657962
TI  - Research in general practice in New Zealand.

PMID- 14657963
TI  - Measuring the quality of general practice in New Zealand.

PMID- 14657964
TI  - Randomised trials in general practice--a New Zealand experience in recruitment.
AB  - AIM: To examine general practitioner (GP) and patient recruitment in a randomised
      clinical trial to determine the usefulness of brain natriuretic peptide (BNP) in
      the diagnosis of heart failure in the community. METHODS: Different techniques
      were used to maximise GP recruitment including early consultation with GPs,
      benefits for participating GPs and patients, and a comprehensive suburb-by-suburb
      approach to GPs using letters and personal visits. GPs then referred patients. At
      the conclusion of the study, GPs were given a questionnaire focussing on barriers
      to referral and reasons for participation. RESULTS: Three hundred and twenty
      seven GPs from 135 practices were sent an introductory letter; 294 were eligible
      to participate. Of these, 186 GPs (63% of eligible GPs) agreed to participate.
      Ninety two GPs (31% of eligible GPs) from 62 practices referred 307 patients to
      the study (range 1-14 patients). There were no significant differences between
      referring and non-referring GPs with respect to sociodemographic characteristics.
      Referring GPs were very supportive of GP participation in research and strongly
      agreed that GPs should be reimbursed for involvement in trials. CONCLUSIONS:
      Patient recruitment by GPs may be aided by the use of a range of strategies
      including financial reimbursement. GPs who agree to participate will not always
      recruit patients. Closer collaboration and understanding between primary
      healthcare professionals and researchers may further enhance recruitment to
      clinical trials.

PMID- 14657965
TI  - A practical approach to quality improvement: the experience of the RNZCGP
      practice standards validation field trial.
AB  - AIM: This paper describes the development, implementation and validation of
      general practice standards, supported by a continuous quality improvement (CQI)
      process that teaches practice teams how to work together to identify and enhance
      the quality of care they provide. METHODS: Practice standards were developed
      through consensus by key stakeholders in general practice, pre-tested in four
      practices, and refined and piloted in 20 practices throughout New Zealand during
      1999. A further field trial was undertaken to validate the standards and test the
      process of practice assessment. During 2000-2001, 74 practices volunteered to be
      assessed against the standards. Sixty one general practitioners, practice nurses
      and practice managers, nominated from independent practitioner associations
      (IPAs) or primary care organisations (PCOs), were trained to undertake the
      assessments. RESULTS: On five of 13 variables, no statistically significant
      differences at the 0.05 level were identified between the practices in the field
      trial and a random sample of practices studied by Kljakovic. The Royal New
      Zealand College of General Practitioners (RNZCGP) standards were found to have
      excellent face validity and content validity, and good construct validity.
      Internal consistency was fair. Lessons from the evaluation have informed an
      improved version of the practice assessment tool. CONCLUSIONS: The validation
      field trial provided the RNZCGP with a framework and tool for an accreditation
      process based on the principles of CQI. The tool offers patients and other
      stakeholders a credible measure of quality and safety at the practice level
      through a process bridging quality control and quality improvement.

PMID- 14657966
TI  - Contraception before and after termination of pregnancy: can we do it better?
AB  - AIM: To compare contraceptive use pre- and post-therapeutic abortion in 1995,
      1999 and 2002 in a New Zealand clinic. METHODS: Retrospective, consecutive case
      review of women presenting for therapeutic abortion. Anonymous data included
      demographic details, contraception used at conception, and post-termination
      contraception. RESULTS: Pre-conception contraceptive use is significantly
      declining, with post-termination condom choice increasing. This is predominantly
      due to increasing numbers of Asian women presenting for abortion. In 2002, 97% of
      Asian women used no contraception or only condoms pre-conception, and 62% chose
      condoms or abstinence post-termination. Oral contraceptives are used
      significantly less by Asian than European women both pre-termination (p = 0.0002)
      and post-termination (p = 0.00001). Other ethnic groups showed little change in
      contraceptive use over the study periods. CONCLUSIONS: It is speculated that
      ethnic Chinese women lack adequate contraceptive education, demonstrate distrust
      of non-barrier methods, believe men should provide the prophylactic, and
      mistakenly believe contraception unnecessary for the first week following
      menstruation. Abortion may be used for family planning rather than as back up for
      contraceptive failure. Young Chinese arriving in New Zealand require immediate
      sexual health education including accurate contraceptive information. Liaison
      between primary healthcare sectors and policy makers of immigration and other
      services assisting overseas students is recommended to provide culturally
      appropriate education.

PMID- 14657967
TI  - Registered and unregistered patients in general practice: implications for
      primary health organisations.
AB  - AIMS: To describe differences between registered and unregistered patients in New
      Zealand general practice and assess patient registers prior to enrollment in
      primary health organisations (PHOs). METHODS: Patient records from 35
      computerised general practices made up the study data set. Data were assessed for
      the year 1 July 2000 to 30 June 2001. Patient registers and consultation files
      were examined to determine levels of recording of demographic data, consulting
      rates and date of last contact with practice for registered and unregistered
      patients. Prescription medications were coded to therapeutic groups for both
      patient groups. RESULTS: Sixty seven per cent of patients were listed as not
      registered with their practice. Only 10% of unregistered patients consulted
      during the study year. At least 20% of all patients had no contact with their
      practice in the last three years. A high proportion of unregistered patients were
      aged 15-34 years. Unregistered patients were likely to be treated for minor
      ailments. CONCLUSIONS: Unregistered patients constitute a distinct patient sub
      population, with fewer holders of community service cards and high user health
      cards than registered patients, and they have a different age/sex profile. A
      substantial number of patients, both registered and unregistered, have had no
      contact with their practice in the last three years. Patient registers will
      require considerable updating prior to PHO enrollment.

PMID- 14657968
TI  - Prescribing for teenagers in New Zealand general practice.
AB  - AIM: To describe patterns of prescribing in general practice for New Zealanders
      aged 13 to 19 years. METHODS: The computerised records of 225 348 consulting
      patients from 48 general practices from around New Zealand were examined. A
      subset of 20 216 consulting patients (53.2% female) aged 13 to 19 years was
      selected and their prescribed medications analysed. General practice prescribing
      was described in terms of demographic characteristics and health-card
      eligibility. RESULTS: Patients aged 13 to 19 consult and are prescribed to less
      than the population as a whole (3.2 consultations versus 5.0, and 2.4 scripts
      versus 4.9 per annum). Females were prescribed to more frequently than males (2.7
      prescriptions per consulting patient per annum versus 2.0). Patients with a
      community services card were prescribed to more frequently than those without
      (2.9 prescriptions per consulting patient per annum versus 2.0). Respiratory
      drugs were most frequently prescribed (primarily anti-asthma medications),
      followed by medications for the treatment of infections, the genito-urinary
      system (mainly oral contraceptives), dermatological medications, and medications
      for treatment of the nervous system (mainly analgesics). CONCLUSIONS: Patients
      aged 13 to 19 consult and are prescribed to less frequently than the population
      as a whole. Asthma appears to be the major source of chronic illness for this
      population. Prescribing data presented here provide valuable baseline data for
      further research.

PMID- 14657969
TI  - Small-cell carcinoma of the ampulla of Vater and a paraneoplastic syndrome.

PMID- 14657970
TI  - Thalamic haemorrhage: a rare presentation of vein of Galen aneurysmal
      malformation in infancy.

PMID- 14657971
TI  - Another myth perpetuated.

PMID- 14657972
TI  - Last time around for DTCA.

PMID- 14657973
TI  - The Composite International Diagnostic Interview (CIDI-Auto): problems and
      remedies for diagnosing panic disorder and social phobia.
AB  - In a recent study of treatment for panic disorder in primary care, the Composite
      International Diagnostic Interview (CIDI-Auto) was used to provide psychiatric
      diagnoses. However, during and after data collection, it was discovered that the
      CIDI appeared to place, or fail to place, a substantial number of people into
      diagnostic categories in ways that conflicted with the investigators' clinical
      experience. The wording of questions in the panic module, coupled with a lack of
      structured follow-up probes, resulted in apparent false negatives for panic
      disorder. Moreover, patients who would otherwise meet criteria for panic disorder
      or social phobia did not receive a diagnosis based on rules that may be
      discordant with clinical practice and, at times, the design of the DSM-IV. For
      this study, changes were made to the interview, including additional probes for
      the panic disorder module and modification of the decision rules used to assign
      or rule out diagnoses of panic disorder and social phobia. The changes resulted
      in greater inclusion of patients in the panic disorder and social phobia
      diagnostic categories and we argue that these changes to the CIDI-Auto increase
      the clinical validity of this instrument. We did not examine the false positive
      rate for the unmodified or modified CIDI, but this is an important issue that
      needs to be evaluated in future research.

PMID- 14657974
TI  - Brief measure of expressed emotion: internal consistency and stability over time.
AB  - The study examined three methodological aspects of expressed emotion (EE) as
      assessed in the course of PACE (Psychosocial Assessment of Childhood Experiences)
      interviews with a parent. In a sample of 87 children, aged 6 13 years, enrolled
      in a prospective study examining the role of stress on the course of asthma, EE
      was assessed at three time points, 9 months apart. A high degree of agreement was
      found among the three concurrent measures of negative and positive EE (kappas
      from 0.74 to 0.97, and from 0.45 to 0.88, respectively; p < or = 0.0001 in all
      instances). The temporal stability of all measures was lower, although
      statistically significant in all but 2 instances (kappas from 0.19 to 0.59, and
      from 0.11 to 0.39, respectively). The temporal stability across measures, as well
      as across interviewers and over time, was broadly similar (kappas from 0.21 to
      0.56 for negative EE, and from 0.09 to 0.38 for positive EE, with all but three
      of the 36 statistically significant). The findings provide support for the
      underlying assumptions of the PACE-EE and show the utility of measures based on
      just very brief periods of non-directive interviewing, making them practical in a
      wide range of studies with EE just one of a larger set of measures.

PMID- 14657975
TI  - A confirmatory factor analysis of the Brief Psychiatric Rating Scale in a
      homeless sample.
AB  - This study used a confirmatory factor analysis procedure, the Oblique Multiple
      Group Method (OMG), with the Brief Psychiatric Rating Scale (BPRS) on a sample of
      homeless individuals who had both a severe mental illness and a substance use
      disorder. The hypothesized five-factor model of Guy (1976) accounted for 93% of
      the possible variance, and all the appropriate scales had their highest loading
      on their respective hypothesized factor. In addition, the Guy model accounted for
      more variance than did an alternative model. The five factors were labelled:
      thinking disorder, anergia, anxiety-depression, hostility-suspicion, and
      activity.

PMID- 14657976
TI  - Inter-rater reliability of the Brief Psychiatric Rating Scale and the Groningen
      Social Disabilities Schedule in a European multi-site randomized controlled trial
      on the effectiveness of acute psychiatric day hospitals.
AB  - The objectives of this study were to report the inter-rater reliability of the
      Brief Psychiatric Rating Scale (BPRS 4.0) and the Groningen Social Disabilities
      Schedule (GSDS-II) as assessed in a randomized controlled trial on the
      effectiveness of psychiatric day hospitals spanning five sites in countries of
      Central and Western Europe. Following brief training sessions, videotaped BPRS
      interviews and written GSDS-vignettes were rated by clinically experienced
      researchers from all participating sites. Inter-rater reliability often proved to
      be poor for items assessing the severity of both psychopathology and social
      dysfunction, but findings suggest that both instruments allow for the assessment
      of the presence or absence of specific psychopathological symptoms or social
      disabilities. Inter-rater reliability at subscale level proved to be good for
      both instruments. Results indicate that, with a brief training session and proper
      use of the instruments, psychopathology and social disabilities can be reliably
      assessed within cross-national research studies. The results are of particular
      interest given that the need to conduct cross-national multi-site studies
      including countries with different cultural backgrounds increases.

PMID- 14657977
TI  - Aims, design and methods of the Smoking and Nicotine Dependence Awareness and
      Screening (SNICAS) study.
AB  - The objectives of the Smoking and Nicotine Dependence Awareness (SNICAS) study
      are to provide nationally representative data on the prevalence of smoking and
      smoking dependence of primary care patients and the frequency in which smoking
      cessation interventions are offered and provided in primary care. With the
      inclusion of both providers' (doctor) and patients' perspectives, the study also
      attempts to identify the needs and motivational status for smoking cessation as
      reported by the patients and as perceived by the doctor. The Smoking and Nicotine
      Dependence Awareness study uses a two-stage epidemiological design. Stage 1
      consists of a pre-study characterization of a nationwide sample of 889 primary
      care doctors (conservative response rate: 50%). Stage 2 consists of a cross
      sectional assessment of unselected consecutive patients (n = 28,707, conservative
      response rate: 52.8%) on the study's target day, by means of patient
      questionnaire and a structured clinical appraisal of each patient by the doctor.
      This paper provides an overview of the design and methods of the study, informs
      about sampling and response rates, and examines whether the study sample could be
      considered representative of German primary care doctors.

PMID- 14657978
TI  - Use of methadone for neuropathic pain.

PMID- 14657979
TI  - Burning mouth syndrome and other oral sensory disorders: a unifying hypothesis.
AB  - Burning Mouth Syndrome (BMS) is a sensory disorder which results in constant,
      bilateral burning pain of the tongue, lips, and other oral mucous membranes.
      Atypical odontalgia (AO) is another sensory disorder, usually defined as a
      toothache-like pain for which no dental cause can be identified. Previous
      literature has suggested that AO is often associated with a concomitant
      temporomandibular disorder (TMD). This hypothesis paper explores the possibility
      that BMS, AO and TMD can be related through hyperactivity of both the sensory and
      motor components of the trigeminal nerve following loss of central inhibition as
      a result of taste damage in the chorda tympani and/or the glossopharyngeal
      nerves.

PMID- 14657980
TI  - Does participation in a pain course based on the International Association for
      the Study of Pain's curricula guidelines change student knowledge about pain?
AB  - BACKGROUND: The People in Pain course was set up as a joint initiative of the
      Departments of Occupational Therapy and Physiotherapy within the School of Health
      and Rehabilitation Sciences at The University of Queensland. It was instigated in
      response to the publication of Pain Curricula for Occupational Therapy and
      Physiotherapy by the International Association for the Study of Pain (IASP) in
      1994 (1). The first year it was offered, the "People in Pain" course comprised 14
      h of lecture content. It was then expanded to encompass 28 h of lectures and
      seminar involvement. OBJECTIVES: To evaluate the impact of participation in a
      university pain course that meets the IASP pain curricula guidelines to increase
      health professional students' knowledge about pain. METHODS: Students who
      participated in the People in Pain course over the first three years were invited
      to complete the Revised Pain Knowledge and Attitudes Questionnaire (R-PKAQ) pre-
      and postcourse. Data obtained from 22 students in the short course formed a pilot
      project, and data from 22 students in the longer version of the course were used
      in the present study. RESULTS: Examination of the correlation matrix indicated
      substantial correlations between all R-PKAQ subscales except physiological basis
      of pain and pharmacological management of pain. In both the pilot project during
      the first year of the course and the expanded course in the following two years,
      significant improvement was found in the students' knowledge on five of the six
      subscales of the R-PKAQ: physiological basis of pain, psychological factors of
      pain perception, assessment and measurement of pain, cognitive-behavioural
      methods of pain relief, and pharmacological management of pain. Improvements in
      the developmental aspects of pain perception subscale failed to reach
      significance. CONCLUSIONS: An integrated pain course developed according to the
      pain curriculum guidelines developed by the IASP resulted in increased student
      knowledge regardless of the length of the program attended.

PMID- 14657981
TI  - Evaluation of dosing guidelines for use of controlled-release codeine in chronic
      noncancer pain.
AB  - OBJECTIVE: The clinical utility of guidelines for conversion of patients from a
      combination analgesic preparation of acetaminophen 300 mg plus codeine 30 mg
      every 4h to 6h as needed to scheduled controlled-release (CR) codeine every 12h
      was evaluated. METHODS: Adult patients with chronic noncancer pain underwent a
      two-week evaluation on acetaminophen plus codeine, followed by eight weeks of
      treatment with CR codeine. Patients taking four to six tablets of acetaminophen
      plus codeine per day were transferred to 50 mg CR codeine every 12 h; those on
      seven to nine tablets were transferred to 100 mg every 12 h; those on 10 to 12
      tablets were transferred to 150 mg every 12 h; and those on greater than 12
      tablets were transferred to 200 mg every 12 h. Subsequent dose adjustments were
      permitted. Acetaminophen (325 mg) was available for rescue. Pain intensity (five
      point categorical and 100 mm visual analog scale), pain related disability,
      adverse events and acceptability were assessed. RESULTS: Of the 140 patients
      enrolled, 95 completed eight weeks of treatment with CR codeine. During month 1
      and month 2, the mean CR codeine daily doses were 295.7+/-119.1 mg and 390.3+/
      163.4 mg, respectively. Pain scores during both CR codeine month 1 and 2 were
      significantly lower than on acetaminophen plus codeine (53.6+/-20.9 mm and 49.7+/
      23.7 mm versus 59.6+/-17.5 mm; P=0.0003, P=0.0001, respectively). CR codeine
      treatment was rated as moderately or highly acceptable by 82% of patients
      compared with 50% for acetaminophen plus codeine (P=0.001). Only seven patients
      (5.9%) discontinued CR codeine treatment because of adverse events. CONCLUSION:
      The results confirm the safety, efficacy and patient acceptability of the initial
      conversion and maintenance dosing recommendations for CR codeine from a
      combination opioid/nonopioid analgesic.

PMID- 14657982
TI  - Methadone in the treatment of neuropathic pain.
AB  - BACKGROUND: Methadone, being an N-Methyl-D-Aspartate receptor antagonist, may
      have a potential role in the treatment of neuropathic pain. OBJECTIVES: To
      evaluate the effect of methadone in the treatment of neuropathic pain and to
      estimate the possible dose ranges needed for pain control. METHODS: Methadone was
      offered as a treatment option to consecutive cancer and noncancer patients with
      neuropathic pain. Pain intensity was measured by the visual analogue scale (VAS)
      (0-10 cm where 0 = no pain and 10 = worst possible pain). Mechanical allodynia
      and paroxysmal (shooting) pain were assessed clinically. All assessments were
      collected prospectively before treatment and once a stable dose of methadone was
      reached. RESULTS: A total number of 18 patients met our inclusion criteria. The
      mean pretreatment VAS +/- SD was 7.7+/-1.5 cm and this dropped significantly to
      1.4+/-1.7 cm on a stable dose of methadone (P<0.0001). Nine of 13 patients (70 %)
      had a complete resolution of mechanical allodynia and all eight patients (100%)
      with shooting pain reported a complete response. The median stable dose of
      methadone was 15 mg per day. CONCLUSION: Methadone at relatively low doses seems
      to be useful in the treatment of neuropathic pain.

PMID- 14657983
TI  - The impact of sampling and measurement on the prevalence of self-reported pain in
      Canada.
AB  - BACKGROUND: Pain is an important public health problem in Canada. International
      estimates of general population pain prevalence range from 2% to 46%. OBJECTIVES:
      The purpose of this paper is to critically examine the potentially misleading use
      of overall prevalence estimates in the pain literature and to use two Canadian
      population-based surveys to assess the impact of sampling and measurement on
      prevalence. METHODS: Two of the secondary data sets used were the 1996/97
      National Population and Health Survey (NPHS) and the Canadian Multicentre
      Osteoporosis Study (CaMos). This paper is based on the assessment of chronic pain
      in the NPHS, and the assessment of short term pain using the Medical Outcomes
      Trust's 36-item health survey and the Health Utilities Index, both collected by
      CaMos. Data are presented as frequencies and percentages overall and stratified
      by age and sex. CaMos prevalence estimates were age- and sex-standardized to the
      NPHS population. RESULTS: The overall prevalence of pain was 39% for one-week
      pain, 66% for four-week pain and 15% for chronic pain. Women were more likely to
      report pain than men and the prevalence of pain increased with age. CONCLUSIONS:
      This study yields useful information about the self-reported responses to a
      variety of questions assessing pain in the general population. Responses to the
      different questions likely represent different categories of pain, such as short
      term versus chronic pain, which in turn may have different epidemiological risk
      factors and profiles. Longitudinal studies of the epidemiology, predictors and
      natural history of chronic pain are urgently needed in the Canadian population.

PMID- 14657984
TI  - Using molecular markers to assess the effect of introgression on quantitative
      attributes of common bean in the Andean gene pool.
AB  - Progress in bean breeding programs requires the exploitation of genetic variation
      that is present among races or through introgression across gene pools of
      Phaseolus vulgaris L. Of the two major common bean gene pools, the Andean gene
      pool seems to have a narrow genetic base, with about 10% of the accessions in the
      CIAT core collection presenting evidence of introgression. The objective of this
      study was to quantify the degree of spontaneous introgression in a sample of
      common bean landraces from the Andean gene pool. The effects of introgression on
      morphological, economic and nutritional attributes were also investigated.
      Homogeneity analysis was performed on molecular marker data from 426 Andean-type
      accessions from the primary centres of origin of the CIAT common bean core
      collection and two check varieties. Quantitative attribute diversity for 15
      traits was studied based on the groups found from the cluster analysis of marker
      prevalence indices computed for each accession. The two-group summary consisted
      of one group of 58 accessions (14%) with low prevalence indices and another group
      of 370 accessions (86%) with high prevalence indices. The smaller group occupied
      the outlying area of points displayed from homogeneity analysis, yet their
      geographic origin was widely distributed over the Andean region. This group was
      regarded as introgressed, since its accessions displayed traits that are
      associated with the Middle American gene pool: high resistance to Andean disease
      isolates but low resistance to Middle American disease isolates, low seed weight
      and high scores for all nutrient elements. Genotypes generated by spontaneous
      introgression can be helpful for breeders to overcome the difficulties in
      transferring traits between gene pools.

PMID- 14657985
TI  - QTL associations for density and diameter in Pinus radiata and the potential for
      marker-aided selection.
AB  - A large full-sib family of radiata pine ( Pinus radiata Donn. ex D. Don) was used
      for quantitative trait locus (QTL) detection and independent verification. QTL
      detection experiments were carried out for juvenile wood density (JWD) and stem
      diameter at breast height (DBH) using selective genotyping. Evenly spaced RFLP
      and microsatellite markers were selected from an existing linkage map. QTLs were
      verified in an independent set of progeny from the same family. Based on map
      location, at least eight QTL positions for JWD and two for DBH were detected and
      verified. The percent variance accounted for by the markers ranged from 0.78% to
      3.58%, suggesting a genomic architecture of many genes with small effect. Two
      unrelated "bridging" families were chosen as candidates for marker-aided
      selection (MAS), and six microsatellite markers showing an association with JWD
      or DBH were tested in these families. Of these, four markers showed a consistent
      association with JWD in one or both of the bridging families. Results from this
      study provide a basis for MAS in P. radiata.

PMID- 14657990
TI  - Congenital anterior urethrocutaneous fistula associated with urethral
      duplication.
AB  - Congenital anterior penile urethral fistula is a rare anomaly; only seven cases
      have been reported to date. This report outlines the clinical presentation and
      the embryologic mechanism of a case associated with urethral duplication.

PMID- 14657991
TI  - Enterobius vermicularis and perianal sepsis in children.
AB  - Specific aetiological factors are responsible for a significant proportion of
      cases of perianal sepsis in children. A rarely implicated pathogen is Enterobius
      vermicularis, an obligate parasite with a ubiquitous presence in children. The
      authors describe two unequivocal instances of threadworm involvement in perianal
      sepsis, suggesting a pathophysiological basis.

PMID- 14657992
TI  - Pierre-Robin syndrome associated with Chiari type I malformation.

PMID- 14657994
TI  - Simultaneous repair of myelomeningocele and shunt insertion.
AB  - METHODS: Simultaneous shunt placement and neural tube repair are described and
      compared with a concomitant series of patients with delayed shunting. Twenty
      eight patients with a myelomeningocele underwent closure of neural tube defects
      at our Institution from 1998 to 2001. Eleven patients (Group 1) had concomitant
      surgery performed after birth. Group 2 (7 out of 28) included patients without
      hydrocephalus at birth, in Group 3 (4 out of 28) the children did not develop
      hydrocephalus, and Group 4 (6 out of 28) patients were born outside our hospital
      and referred for surgical care after birth. DISCUSSION: Simultaneous insertion of
      shunt and correction of a myelomeningocele do not pose an additional risk to the
      child and do have some advantages, facilitating healing of the back without CSF
      leakage and protecting the brain from the effects of progressive ventricular
      dilatation. Patients with a myelomeningocele born outside the hospital are prone
      to infectious complications.

PMID- 14657995
TI  - Medulloblastoma with extensive nodularity: a variant occurring in the very young
      clinicopathological and immunohistochemical study of four cases.
AB  - CASE REPORT: Four cases of medulloblastoma with extensive nodularity (MBEN) are
      described. The patients were 3 years of age or younger at diagnosis. Cranial CT
      scan disclosed multiple coalescing nodules with peculiar 'grape-like'
      architecture in three patients. A near total excision of the tumour was performed
      in all four patients. The patients are currently receiving radiation and
      chemotherapy. Histologically, the tumours were characterized by extreme
      nodularity with intranodular uniformity and low proliferative index. The
      internodular zones were extremely cellular, composed of undifferentiated,
      mitotically active cells. Bcl-2 protein expression was observed in the cellular
      zones but was distinctly absent within nodules. DISCUSSION: MBEN represents a
      variant that occurs in very young children but has a good prognosis. The
      favourable outcome is probably related to its spontaneous neurocytic
      differentiation. The pattern of Bcl-2 immunoreactivity in MBENs indicates that
      this protein could be a key player in the regulation of neuronal differentiation
      in medulloblastomas.

PMID- 14657996
TI  - Neuroprostheses to treat neurogenic bladder dysfunction: current status and
      future perspectives.
AB  - BACKGROUND: Neural prostheses are a technology that uses electrical activation of
      the nervous system to restore function to individuals with neurological or
      sensory impairment. INTRODUCTION: This article provides an introduction to neural
      prostheses and lists the most successful neural prostheses (in terms of implanted
      devices). CURRENT TREATMENT: The article then focuses on neurogenic bladder
      dysfunction and describes two clinically available implantable neural prostheses
      for treatment of neurogenic bladder dysfunction. Special attention is given to
      the usage of these neural prostheses in children. FUTURE TREATMENT: Finally,
      three new developments that may lead to a new generation of implantable neural
      prostheses for bladder control are described. They may improve the neural
      prostheses currently available and expand further the population of patients who
      can benefit from a neural prosthesis.

PMID- 14657997
TI  - Pierre-Robin syndrome associated with Chiari I malformation.

PMID- 14657998
TI  - How does the cold stenothermal gadoid Lota lota survive high water temperatures
      during summer?
AB  - The cold-stenothermal freshwater gadid Lota lota inhabiting the potamic regions
      of lowland rivers in central Europe, is exposed to summer temperatures up to 25
      degrees C, which is far above the thermal preferendum of this species. Oxygen
      consumption rates, determined in field catches sampled at different times of the
      year, revealed that the basal metabolic rate is depressed during summer when
      water temperatures are high (152+/-16 micromol O2 100 g(-1) h(-1)at 22 degrees C
      in July compared to 250+/-33 micromol O2 100 g(-1) h(-1) at 6 degrees C in
      November). This observation led us to investigate whether the observed depression
      of the metabolic rate is caused by oxygen limitation due to thermal impairment of
      the ventilatory system, as has been observed in other species. Determination of
      anaerobic end products (lactate and succinate) in the liver tissue of fish caught
      at different sampling dates did not show an accumulation of anaerobic end
      products during the summer, indicating no oxygen limitation. Measurements of
      enzyme activities in the white musculature and liver suggest that enzymes
      involved in aerobic metabolism were down-regulated during summer, which may have
      contributed to the observed reduction of metabolic rate.

PMID- 14657999
TI  - Contemporary management of penile cancer including surgery and adjuvant
      radiotherapy: an experience in Taiwan.
AB  - This retrospective study reports on the treatment outcomes of 45 men with penile
      cancer and seeks to address the issue concerning the treatment of inguinal lymph
      nodes (LN). Of these 45 patients, five had verrucous carcinoma and the other 40
      had squamous cell carcinoma. Eighteen patients had inguinal lymph nodes (LNs)
      metastasis and received treatments of inguinal LNs involving bilateral inguinal
      LN dissection or unilateral inguinal LN dissection with or without postoperative
      radiotherapy. The median follow-up was 37 months. The ultimate local and regional
      controls for patients with verrucous carcinoma were 100 and 100%, respectively.
      Among the 40 patients with squamous cell carcinoma, the overall local control
      rate was 90%. The 5-year overall survival (OS) and disease-free survival (DFS)
      rates of patients without or with pathological inguinal LN metastasis were 70 vs.
      22% (p=0.01), and 55 vs. 16% (p=0.004), respectively. The regional failure rates
      after inguinal LN dissection for pathological inguinal LN metastasis were 11%
      (1/9) and 60% (3/5) in patients with and without adjuvant radiotherapy. This
      study demonstrates that verrucous carcinoma shows excellent treatment outcomes
      following surgery alone. Squamous cell carcinoma of the penis is associated with
      a high incidence of inguinal lymph node metastasis. Elective groin dissection is
      indicated for all penile cancer patients except those with verrucous carcinoma
      and pT1 cancer with well-differentiated tumor. For patients with pathologically
      positive inguinal LN metastasis, adjuvant radiotherapy can increase inguinal
      control in this study. It warrants further prospective trial to prove the value
      of adjuvant radiotherapy in patients with pathological documented inguinal LN
      metastasis in penile cancer.

PMID- 14658000
TI  - Reproducibility of linear tumor measurements using PACS: comparison of caliper
      method with edge-tracing method.
AB  - The aim of this study was to evaluate inter- and intra-observer reproducibility
      when making electronic caliper linear tumor measurements on picture archiving and
      communications systems (PACS) and compare them with linear measurements obtained
      from circumferential tracing of tumor perimeter. Three radiologists measured 64
      masses from 30 patients on body CT scans in two separate settings. Long axis and
      perpendicular short axis were measured using electronic calipers. The edge of
      each tumor was traced electronically and the long and short axes were calculated
      by computer software. The reproducibility of a measurement was evaluated by
      computing and comparing the absolute value of the mean difference between initial
      and subsequent measurements. The mean differences +/-95% confidence interval (CI)
      between two measurements of the long by short axis were 3.8+/-2.6x3.1+/-1.8 mm
      when the caliper method was used and 3.5+/-2.0x3.2+/-1.5 mm when the tumor
      tracing method was used. There was no statistically significant difference in
      individual intra-observer reproducibility of tumor axes measurements. Neither
      long- nor short-axis single-dimension measurements resulted in significantly
      greater or lesser intra-observer reproducibility. When comparing caliper and
      tracing measurements, the overall mean difference (3.42+/-1.8 vs 3.38+/-1.4 mm)
      was not statistically significant. There was close correlation between the
      individual measurements made by each observer whether these were made by
      electronic calipers and when these were calculated from electronic tracings
      (Pearson correlations between 0.79 and 0.949). Current PACS systems allow
      reproducible linear, long or short axis, tumor measurements. There is no
      significant difference in reproducibility of measurements whether these are made
      directly with electronic calipers or calculated from tumor edge tracings.

PMID- 14658001
TI  - Real-time MR with TrueFISP for the detection of acute pulmonary embolism: initial
      clinical experience.
AB  - The feasibility and diagnostic value of real-time magnetic resonance imaging (RT
      MRI) for the diagnosis of acute pulmonary embolism (PE) was evaluated by
      comparing RT-MRI and magnetic resonance angiography (MRA). In 39 consecutive
      patients with suspected PE real-time true fast imaging with steady-state
      precession (TrueFisp) was prospectively compared with contrast-enhanced MRA on a
      1.5-T MR scanner. The TrueFisp sequence used allowed acquisition of T2-weighted
      images at 0.4 s per image so that the pulmonary vasculature could be visualized
      in three orientations in <3 min without the need for breath holding or contrast
      media application. Results of additional scintigraphic pulmonary perfusion
      examinations were available from 17 patients. All 39 primary RT examinations
      (100%) and 30 of 39 MRA examinations (77%) were of diagnostic quality. The
      reasons underlying failure to achieve diagnostic quality for MRA were breathing
      artifacts among dyspneic patients in all 9 cases. Compared with MRA, the
      sensitivities and specificities of RT sequences for PE were 93 and 100% (per
      examination), 96 and 100% (lobar artery PE), and 97 and 100% (segmental artery
      PE), respectively. Compared with scintigraphy, the sensitivity and specificity of
      RT-MRI were 83 and 100%, respectively. The MRA reached 100% sensitivity and
      specificity in this subgroup. The RT-MRI proved to be very robust and undisturbed
      by respiratory movements and patient cooperation. Its image quality assured fast
      diagnostic examinations, and its sensitivity and specificity, compared with MRA
      and scintigraphy, were sufficient to allow the diagnosis of acute central, lobar,
      and segmental PE; therefore, the emergency diagnosis of PE using RT-MRI is
      feasible and reliable.

PMID- 14658002
TI  - Antiannexin V autoantibody in thrombophilic Behcet's disease.
AB  - We propose that thrombosis in Behcet's syndrome may be due to disruption of the
      annexin V shield by antiphospholipid antibodies. Measurement of antiannexin V
      antibodies may be of value in confirming diagnosis and evaluating the risk of
      venous and arterial thrombosis in patients with Behcet's syndrome. To evaluate
      the efficiency of antiannexin V antibody in the formation of thrombosis, 53 male
      patients with Behcet's disease according to international study group criteria
      were involved in this study. The age range was 20-28 years (mean 23+/-3.4). All
      of these patients had been taking colchicum. Those taking medications that
      interfere with antiannexin V autoantibody levels were excluded, and serum samples
      were taken during the active period. Group I included 26 Behcet's patients with
      well-documented thrombosis, group II included 27 Behcet's patients without
      thrombosis, and group III was comprised of 27 healthy controls. There were no
      statistical differences between the mean concentrations of IgG and IgM
      antiannexin V autoantibodies in the three groups. The results indicate that these
      antibodies may not be associated with the pathogenesis of thrombotic events in
      patients with Behcet's syndrome.

PMID- 14658003
TI  - Drug-induced lupus erythematosus secondary to nafcillin: the first reported case.
AB  - With an estimated incidence of 15-30,000 cases per year in the United States,
      drug-induced lupus erythematosus (DIL) is an uncommon iatrogenic condition. The
      number of implicated medications increases each year. We report the first case of
      DIL secondary to nafcillin administration in a patient with a prosthetic aortic
      valve and methicillin-sensitive Staphylococcus aureus who developed a facial rash
      and lower back pain.

PMID- 14658005
TI  - Kaposi's sarcoma in a patient with severe relapsing polychondritis.
AB  - This report describes the case of a young man who developed Kaposi's sarcoma (KS)
      after corticosteroid treatment for severe tracheal involvement of relapsing
      polychondritis (RP). The etiopathogenetic mechanisms that may have led to the
      evolution of this unusual neoplasm are discussed. To our knowledge, this is the
      first case reported of concomitant RP and KS.

PMID- 14658004
TI  - Articular, B-cell, non-Hodgkin's lymphoma mimicking rheumatoid arthritis:
      synovial involvement in a small hand joint.
AB  - Polyarticular joint manifestations as the predominant symptom of non-Hodgkin's
      lymphoma (NHL) are quite rare. In the absence of peripheral lymph node and
      visceral involvement, lymphomas presenting as polyarthritis create a problem for
      the patients as another rheumatic disease. We present a case that had been
      diagnosed with rheumatoid arthritis because of symmetrical articular symptoms.
      The patient later developed severe pain and marked swelling in her right fourth
      finger, and a diagnosis of septic arthritis and osteomyelitis complicating
      rheumatoid arthritis was assumed. The final diagnosis of NHL with synovial
      involvement could be made only after histopathologic examination of a biopsy
      specimen obtained from the amputated finger. This is the first case report
      demonstrating direct synovial involvement of a small joint in a patient with NHL
      presenting with polyarthritis. Articular and periarticular involvement of
      multiple joints shown by MRI in this patient suggests that direct synovial
      involvement may be responsible for the polyarticular symptoms in such patients.

PMID- 14658006
TI  - Proposal for a sonographic classification of target joints in rheumatoid
      arthritis.
AB  - OBJECTIVE: The purpose of this study was to classify sonographically the joint
      damage of target joints in patients with rheumatoid arthritis (RA). METHODS:
      During a 3-year cross-sectional study, standardized arthrosonography of
      symptomatic target joints was performed in patients with RA. According to those
      findings, a classification with progressive deterioration of joint alteration in
      RA was created that grades visible morphological changes of the joint components.
      Using elbow joints as a subgroup, inter- and intraobserver reliability was
      calculated. RESULTS: Examined and included in this study were 1211 joints of 425
      patients with RA. The mean disease activity score was 5.2 (range 0.75-7.79).
      Sonographically visible changes could be classified and divided into six stages.
      A standardized sonographic evaluation system was developed. In reference to the
      elbow joint, overall percentages for intra- and interobserver reliability of
      sonography were 90.8% and 88.8%, respectively. CONCLUSION: Sonography is a
      valuable tool for assessing and classifying joint alteration in RA. Particularly
      in early stages of joint affection, ultrasound is superior to X-ray in detecting
      soft tissue changes and minor erosions.

PMID- 14658007
TI  - Thrombospondin-1 plus irinotecan: a novel antiangiogenic-chemotherapeutic
      combination that inhibits the growth of advanced human colon tumor xenografts in
      mice.
AB  - Chemotherapy for the treatment of advanced or metastatic colon cancer, utilizing
      agents such as 5-fluorouracil (5-FU) and irinotecan (CPT-11), produce a 5-year
      survival of about 10%. Thus, the identification of new, effective, therapeutic
      regimens to treat this disease remains critically important. To this end,
      selected antiangiogenic agents, compounds that inhibit neovascularization, have
      been shown to produce a modest tumor growth-inhibitory effect with little
      systemic toxicity. Thus these agents are attractive candidates for use with
      conventional chemotherapeutic agents to treat this disease. To evaluate this
      approach, experiments were undertaken to assess the cytotoxic and antineoplastic
      activity of CPT-11 and the antiangiogenic agent thrombospondin-1 (TSP-1) in the
      HT-29 model of human colon cancer. These agents were chosen since CPT-11 is a
      camptothecin analogue efficacious in the treatment of colon cancer and TSP-1 is a
      human glycoprotein that possess antiangiogenic activity. As expected, in vitro
      studies revealed that a 5-day exposure to TSP-1 at concentrations up to 130
      microg/ml was not cytotoxic alone and did not affect the cytotoxicity of CPT-11,
      or of its active metabolite SN38, in HT-29 cells. Similarly, in human umbilical
      vein endothelial cells, TSP-1 alone induced only a slight cell growth-inhibitory
      effect and did not significantly increase the cytotoxicity of either CPT-11 or
      SN38. The antineoplastic activities of TSP-1 and CPT-11 were assessed in athymic
      (nude) female mice bearing advanced subcutaneous xenografts of HT-29 cells. Mice
      received TSP-1 alone (5-40 mg/kg per day) intraperitoneally (i.p.), CPT-11 alone
      (100-300 mg/kg, i.p.), TSP-1 (10 mg/kg per day) plus CPT-11 (125 mg/kg), or TSP-1
      (20 mg/kg per day) plus CPT-11 (150 mg/kg). TSP-1 was injected daily (Monday
      through Friday) for 4 weeks (20 injections in total) whereas CPT-11 was
      administered once weekly on days 0, 7, 14 and 21. By day 28, treatment with TSP-1
      alone (5, 10 or 20 mg/kg per day) induced a dose-dependent inhibition of
      xenograft growth. Further, treatment with 10 or 20 mg/kg per day resulted in an
      average treated tumor size/control tumor size (T/C) on day 28 of 0.68 (range 0.64
      0.71) or 0.58 (range 0.54-0.60), respectively. CPT-11 at all doses significantly
      inhibited tumor growth with an average T/C value of 0.21 (range 0.15-0.27).
      However, the 250 and 300 mg/kg regimens induced significant toxicity and
      mortality. When TSP-1 was combined with CPT-11, a significant ( P< or = 0.05)
      inhibition of tumor growth also was observed (T/C < or = 0.17, range 0.11-0.20).
      Importantly, this enhanced tumor growth inhibition was obtained without
      significant toxicity. The therapeutic implications of these findings are
      discussed.

PMID- 14658008
TI  - Pharmacokinetics and cellular uptake of imatinib and its main metabolite
      CGP74588.
AB  - Despite the remarkable clinical response rates to imatinib in the treatment of
      bcr-abl leukemic patients, pharmacokinetic data on this relatively novel
      substance are needed to improve our understanding of the emergence of resistance,
      the interindividual variations of clinical response and the clinical and biologic
      relevance of its main metabolite N-desmethyl-imatinib. We present here
      pharmacokinetic data obtained with a newly designed HPLC approach in 97 patients
      with chronic myeloid leukemia or acute lymphatic leukemia (ALL) under treatment
      with imatinib that allowed us to calculate the AUC (39.5 microg.h/ml for an oral
      dose of 400 mg daily), the t(1/2) (18.2 h) and the peak concentration (1.92
      micro/ml for an oral dose of 400 mg daily) of imatinib in plasma. In a subgroup
      of patients, the same parameters were analyzed for N-desmethyl-imatinib. We also
      provide data on the imatinib concentration in the cerebrospinal fluid (CSF) of
      ALL patients and demonstrate that oral administration of imatinib resulted only
      in a marginal flux across the blood-brain barrier. Finally, in an in vitro
      setting, we determined cellular concentrations of imatinib in HL-60 cells and
      showed an over-proportional uptake both in RPMI medium and in human plasma. Using
      an arithmetical approach combining all parameters obtained in imatinib-treated
      patients, we finally provide a conclusive approximation of basic pharmacokinetic
      data for both imatinib and its main metabolite N-desmethyl-imatinib.

PMID- 14658009
TI  - Intravascular lymphoma associated with hemophagocytic syndrome: a rare but
      aggressive clinical entity.
AB  - We report a 55-year-old male with a diagnosis of intravascular lymphoma and
      hemophagocytosis. He initially presented with hemolytic anemia and splenomegaly
      and was successfully treated with oral steroids. His clinical course was later
      complicated by fever, cytopenias, hypoalbuminemia, disseminated intravascular
      coagulation, gastrointestinal bleeding and acute tubular necrosis. Results of an
      extensive investigation for fever of unknown origin were negative. Although the
      patient was treated aggressively with antimicrobials, transfusion support and
      dialysis, he expired 3 weeks after hospitalization. Post-mortem analysis revealed
      large CD30- and CD45-positive lymphoma cells in an intravascular distribution in
      most of the organs studied. Histopathology of the spleen and bone marrow was
      significant for fulminant hemophagocytosis.

PMID- 14658010
TI  - Neutropenic enterocolitis: a serious complication during the treatment of acute
      leukemias.
AB  - Neutropenic enterocolitis (NE) is a severe gastrointestinal complication in
      patients who undergo aggressive chemotherapy. It is a necrotizing inflammation of
      the cecum, colon, and the terminal part of the ileum. The serious clinical state
      of NE patients requires very frequent surgical consultations; however, in a few
      particular cases of NE, e.g., perforation of the bowels, a surgical intervention
      is necessary. Here, we report on six cases of NE in patients with acute
      leukemias. The patients were all women aged 21-55 years. Two of them had acute
      myeloid leukemia and four had lymphoblastic leukemia. NE occurred 7-10 days after
      the completion of chemotherapy, during the neutropenic phase. They represented a
      typical picture of NE: two of them died because of septic shock; five patients
      had subileus with irritation of the peritoneum; and one had hepatosplenic
      abscesses confirmed 6 months later by post-mortem examination. In each case, a
      surgical opinion was required. None of these patients were operated on. We
      present a report summarizing our experience and problems with six patients who
      had a clinical picture of NE and offer a short review of the current literature
      on the subject.

PMID- 14658011
TI  - Combined therapy with deferiprone and desferrioxamine successfully regresses
      severe heart failure in patients with beta-thalassemia major.
AB  - Cardiac complications caused by iron deposition are major causes of death in
      patients with beta-thalassemia major. Deferiprone (L1) was found to have greater
      efficacy at depleting myocardial iron than desferrioxamine (DFX). Furthermore,
      combined therapy with L1 and DFX produced an additive or synergistic iron
      chelating effect. We report the successful treatment of severe heart failure in
      two patients with beta-thalassemia major with the combined therapy. Magnetic
      resonance images showed a marked recovery of signal intensity in the heart,
      indicating a significant reduction of iron load in the heart. No significant
      adverse effects were noted. Therefore, combined therapy with L1 and DFX should be
      considered in patients with beta-thalassemia major and cardiac complications.

PMID- 14658014
TI  - The course of the posterior inferior cerebellar artery may be related to its
      level of origin.
AB  - The course of the posterior inferior cerebellar artery (PICA) was analyzed with
      reference to its origin and relationships with the medullary and cerebellar
      surfaces and the adjacent cranial nerves in 40 brains after the injection with
      acrylic resins of the vertebrobasilar system. In 42.5% of instances, the PICA
      originated from the lateral medullary segment of the vertebral artery (VA), in
      32.5% from its premedullary segment, in 22.5% from the basilar artery (BA), and
      in 2.5% it was absent. With reference to the level of origin, three patterns of
      course for the lateral medullary segment of the PICA can be outlined. (1) When it
      arises from the lateral medullary segment of the VA, it passes below the
      hypoglossal nerve, and the lateral medullary segment may form a loop with an
      anterosuperior convexity towards the pontomedullary sulcus (41%), or it may
      follow a rectilinear course (41%). It passes at the level of the accessory nerve.
      The tonsillomedullary (TM) segment shows a caudal loop and the telovelotonsillary
      (TVT) has a cranial loop. (2) When the PICA arises from the BA, it passes above
      the hypoglossal nerve. The lateral medullary segment forms a loop with lateral
      convexity (78%) and passes above or through the glossopharyngeal nerve,
      frequently showing a recurrent course among the roots of the IX, X, or XI cranial
      nerve. The TM and the TVT segments do not have loops. (3) When the PICA arises
      from the premedullary segment of the VA, it passes above, below, or through the
      rootlets of the hypoglossal nerve. In the lateral medullary segment, it follows a
      rectilinear course (54%) and passes the plane formed by the IX, X, and XI cranial
      nerves at an intermediate level with respect to the other two patterns. The TM
      and the TVT segments show caudal and cranial loops. The different origins and
      courses of the PICA derive from the selection of different branches of the
      primitive vertebrobasilar plexus during the development of the cerebellum. The
      existence of an embryologic correlation between the course of the PICA and its
      level of origin may be useful in the evaluation of its angiographic anatomy.

PMID- 14658016
TI  - Estimation of contaminant depletion in unsaturated soils using a reduced-order
      biodegradation model and carbon dioxide measurement.
AB  - The objective of this study was to develop a reduced-order model of
      biodegradation in unsaturated soils that allows the estimation of contaminant
      depletion, using available on-line measurements. Hexadecane was chosen as a model
      compound for petroleum hydrocarbons. A two-compartment model was developed,
      decoupling the intrinsic biodegradation kinetics from limiting factors imposed by
      field conditions, such as oxygen transfer and contaminant bioavailability. Two
      new experimental protocols (one for the liquid phase and the other for the solid
      phase) were developed to monitor hexadecane depletion, hexadecane mineralization,
      total mineralization, and evolution of the degraders. Using the liquid-phase
      experiment, parameters of a Haldane kinetic model and yield coefficients were
      identified and used in the complete model of biodegradation in soil. Using the
      carbon dioxide production curve, a biocontact kinetic model was identified so
      that, despite the high sensitivity of the model outputs to variations in the
      parameters, hexadecane depletion could be correctly predicted with an average
      error on the entire time trajectory of about 8%. Moreover, the ratio between
      hexadecane mineralization and total mineralization remained constant after a
      brief transient period, indicating that hexadecane mineralization could be
      deduced from the total carbon dioxide measurement. Finally, the new model
      developed in this study allows real-time monitoring of contaminant
      biodegradation, using on-line carbon dioxide measurement.

PMID- 14658017
TI  - Dose and image quality. How does the choice of kilovoltage affect patient dose,
      scattered radiation, and image quality in CT examinations? Submitted by Glen
      Thomson, Middlemore Hospital, New Zealand.

PMID- 14658015
TI  - Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy:
      normalisation by acute angiotensin-converting enzyme inhibition.
AB  - The purpose of this study was to assess whether acute angiotensin-converting
      enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve
      in a subpopulation of normotensive patients with diabetes and left ventricular
      hypertrophy (LVH), both independent risk factors of coronary disease. Using
      positron emission tomography (PET), we investigated the response of regional
      myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat
      (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients
      with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia
      infused at rest and during dipyridamole hyperaemia. Twelve healthy control
      subjects were included in the study, five of whom were also studied with
      perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients
      was 123+/-7/65+/-9 mmHg. Compared with controls, maximal perfusion was reduced in
      patients (1.8+/-0.6 vs 2.5+/-1.0 ml min(-1) g(-1); P<0.05), and perfusion reserve
      was also lower, at borderline significance (2.7+/-1.0 vs 3.6+/-1.3; P=0.059).
      During perindoprilat infusion, myocardial perfusion reserve in patients increased
      to 3.9+/-0.9 ( P<0.001) due to normalisation of maximal perfusion (2.3+/-0.5 ml
      min(-1) g(-1), P<0.01). In the five control subjects both resting and hyperaemic
      perfusion remained unchanged during perindoprilat infusion. It is concluded that
      acute ACE inhibition with perindoprilat improves maximal achieved myocardial
      perfusion in non-hypertensive patients with diabetes and LVH.

PMID- 14658018
TI  - Referent configuration of the body: a global factor in the control of multiple
      skeletal muscles.
AB  - In addition to local biomechanical and reflex factors influencing muscle
      activation, global factors may be used by the nervous system to control all
      muscles in a coherent and task-specific way. It has been hypothesized that a
      virtual or referent (R) configuration of the body determined by muscle
      recruitment thresholds specified by neural control levels is such a factor. Due
      to the threshold nature of the R configuration, the activity of each muscle
      depends on the difference between the actual (Q) and the R configuration of the
      body. The nervous system modifies the R configuration to produce movement. One
      prediction of this hypothesis is that the Q and R configurations may match each
      other, most likely in movements with reversals in direction, resulting in a
      minimum in the electromyographic (EMG) activity level of muscles involved. The
      depth of the minima is constrained by the degree of coactivation of opposing
      muscle groups. Another prediction is that EMG minima in the activity of multiple
      muscles may occur not only when the movement is assisted but also when it is
      opposed by external forces (e.g., gravity). To verify these predictions, we
      analyzed EMG patterns of 16-21 functionally diverse muscles of the legs, trunk,
      and arms during jumping and stepping in place. One EMG minimum in the activity of
      all muscles regularly occurred near the apex of the jump. A minimum was also
      observed near the point of transition of the body from flexion to extension
      leading to a jump. During stepping in place, the activity of muscles of each side
      of the body was usually minimized near the beginning and near the end of the
      stance phase as well as during the maximum elevation of the foot. Since EMG
      minima occurred not only during gravity-assisted but also gravity-opposed
      movement reversals, it is concluded that neural factors (such as matching between
      the Q and R) rather than mechanical factors are responsible for minimizing the
      EMG activity in these movements.

PMID- 14658019
TI  - Space-independent modality-driven attentional capture in auditory, tactile and
      visual systems.
AB  - Extending previous evidence for attentional shifts across auditory and visual
      modalities without the confound of the two modalities originating at different
      locations (Turatto et al. 2002), we investigated attention shifts between
      auditory and tactile modalities, and between tactile and visual modalities. Two
      stimuli (S1 and S2), either in the same or in different modalities, were
      delivered from the same spatial source and were separated by a variable temporal
      gap. S1 was task irrelevant, whereas S2 required a speeded discrimination.
      Results showed that modality switching is detrimental independently of the
      stimulated modality as long as the temporal lag between S1 and S2 is short enough
      that there is not time to switch attention before S2 is delivered. We observed
      automatic, modality-driven, attentional capture, with ipsimodal trials leading to
      faster response times than crossmodal trials. The present results cannot be
      accounted for by spatial artifacts, response priming or criterion shifts, and are
      interpreted as the consequence of a space-independent attentional shift across
      sensory modalities.

PMID- 14658020
TI  - Biofilms as bio-indicator for polluted waters? Total reflection X-ray
      fluorescence analysis of biofilms of the Tisza river (Hungary).
AB  - The aim of this work was to investigate the heavy metal accumulation by natural
      biofilms living in the catchment area of the Tisza river in Hungary, as well as
      in biofilms cultivated in vitro. Laboratory tests have demonstrated that metals
      can be adsorbed on biofilms, depending on their concentration and on the
      availability of free sorptive places. Biofilms were cultivated in vitro in
      natural freshwater from the Saale river, Germany. After reaching the plateau
      phase, Cu was added to reach a concentration of 100 micro g/L. An increase of its
      mass fraction in the biofilm was observed, which caused the decrease of the
      concentration in the water phase. Unfortunately, the reactor wall was also found
      to act as adsorbent for Cu. More detailed results of our in vitro experiments
      will be published in a forthcoming paper. Naturally grown biofilm samples from
      exposed as well as background places at the Hungarian rivers Szamos and Tisza
      were collected in 2000 and 2002 after the cyanide spill, and analysed using total
      reflection X-ray fluorescence analysis (TXRF). Metal mass fraction differences as
      high as two orders of magnitude were found between polluted and unpolluted
      (background) sampling points. Extremely high concentration values, e.g. 5600
      microg/g Zn in biofilm, were found at highly polluted sampling points. This means
      an enrichment factor of ca. 10,000 compared to the water phase.

PMID- 14658021
TI  - Integrated procedure for determination of endocrine-disrupting activity in
      surface waters and sediments by use of the biological technique recombinant yeast
      assay and chemical analysis by LC-ESI-MS.
AB  - An integrated procedure using mass spectrometry and molecular biology for
      determination of estrogenicity in natural waters and sediments is reported. Solid
      phase extraction (SPE) and pressurized-liquid extraction (PLE), respectively,
      were used for isolation of endocrine-disrupting compounds (EDC) from surface
      waters and sediments, followed by liquid chromatography-mass spectrometry using
      an electrospray interface (LC-ESI-MS). Twenty seven EDC were determined: non
      ionic surfactants (nonylphenol ethoxylate), alkylphenols (e.g. nonylphenol and
      octylphenol), bisphenol A, phthalates, and natural and synthetic steroid sex
      hormones. Limits of detection varied from 0.02 to 0.22 microg L(-1) and from 1 to
      10 microg kg(-1) in water and sediments, respectively. Recoveries ranged from 65
      to 125% and 73 to 97% for waters and sediments, respectively. In addition to LC
      ESI-MS determination, extracts obtained by SPE and PLE were analyzed by the
      recombinant yeast assay (RYA) to assess total estrogenic activity. This bioassay
      detects natural estrogens and xenoestrogens, producing a quantitative measurement
      of EDC irrespective of the identity of the chemical responsible for the activity.
      As a novelty, a relative estrogenicity factor was determined for 19 analytes with
      EC(50) values ranging from 10(-10) to 10(-9) mol L(-1) for synthetic estrogens,
      from 10(-7) to 10(-5) mol L(-1) for alkylphenol derivatives, and from 10(-5) to
      10(-4) mol L(-1) for phthalates and benzothiazoles. By use of this integrated
      chemical-ecotoxicological approach good correlation was usually established
      between chemical composition and estrogenic effects for surface water and
      sediment samples from Portugal. Estrogenic activity observed was mainly
      attributed to the presence of nonylphenolic compounds (with concentrations of NP
      ranging from 0.1 up to 44 microg L(-1) in waters and up to 1172 microg kg(-1) in
      sediments), and to the sporadic presence of estrogens, detected at ng L(-1)
      levels.

PMID- 14658022
TI  - Application of combined approach to analyze the constituents of essential oil
      from Dong quai.
AB  - A combined approach of sub-window factor analysis and spectral correlative
      chromatography has been employed to analyze the constituents of essential oils of
      Dong quai. Essential oils are the main pharmacological active individuals of Dong
      quai. Some constituents in the main root of Dong quai have been identified by GC
      MS with the help of sub-window factor analysis resolving two-dimensional original
      data into mass spectra and chromatograms. Correlative constituents in another
      part of the root fiber have been recognized by spectral correlative
      chromatography. Seventy six of 97 separated constituents in the essential oil of
      main root were identified and quantified, accounting for about 91.36% of the
      total content. Sixty seven correlative components in the essential oil of root
      fiber were recognized. The result proves that the combined approach is powerful
      enough for the analysis of complex herbal samples.

PMID- 14658023
TI  - Flavonoids in Leguminosae: analysis of extracts of T. pratense L., T. dubium L.,
      T. repens L., and L. corniculatus L. leaves using liquid chromatography with UV,
      mass spectrometric and fluorescence detection.
AB  - Reversed-phase LC on C-18 bonded silica with a methanol-ammonium formate gradient
      was used to determine the main flavonoids in leaves of four species of the
      Leguminosae family. The detection modes were diode-array UV absorbance,
      fluorescence, and (tandem) mass spectrometry. LC-UV was used for a general
      screening, sub-classification, and the calculation of total flavonoid contents.
      LC-FLU was included to identify isoflavones on the basis of their native
      fluorescence. Most structural information regarding aglycons, sugar moieties, and
      acidic groups was derived from LC-MS in both the full-scan and extracted-ion
      mode, using negative-ion atmospheric pressure chemical ionization. MS/MS did not
      provide much additional information, because the same fragments were observed as
      in full-scan MS. In T. pratense and T. repens, the main constituents were
      flavonoid glucoside-(di)malonates, while T. dubium and L. corniculatus mainly
      contained flavonoid (di)glycosides. Satellite sets comprising an aglycon, the
      glucoside and glucoside-malonates or -acetates, were abundantly present only in
      T. pratense. Generally speaking, the main aglycons and sugars in the four plant
      species are surprisingly different. In addition, while the results for T.
      pratense are similar to those reported in the literature, there is little
      agreement in the case of the other species. Finally, total flavonoid contents
      ranged from 50-65 mg/g for L. corniculatus and T. dubium, to 15 mg/g for T.
      pratense and only 1 mg/g for T. repens.

PMID- 14658024
TI  - Low-temperature electrothermal vaporization of thenoyltrifluoroacetone complex of
      Sc(III) and Y(III) for sample introduction in an inductively coupled plasma
      atomic emission spectrometry, and their determination in biological samples.
AB  - A new method for inductively coupled plasma atomic emission spectrometry (ICP
      AES) determination of trace Sc and Y, based on gaseous compound introduction into
      the plasma as their thenoyltrifluoroacetone (TTA) complexes by electrothermal
      vaporization was developed. Using the reagent TTA as chemical modifier can not
      only enhance the analytical signals, but also reduce the vaporization
      temperature. At a temperature of 1,000 degrees C the trace Sc and Y can be
      vaporized completely into ICP. The factors affecting the formation of the chelate
      and its vaporization behavior, such as drying time, vaporization
      temperature/time, reaction medium and the amount of TTA, were investigated in
      detail. Under the optimized conditions (drying temperature/time 100 degrees C/10
      s, vaporization temperature/time 1,000 degrees C/4 s), the limits of detection
      for Sc and Y were 19 pg and 34 pg (3sigma), respectively, and the relative
      standard deviations for Sc and Y were 4.2% (cSc=0.2 microg mL(-1); n=7) and 2.6%
      (cY=0.5 microg mL(-1); n=7). The linear ranges of the calibration graphs cover
      three orders of magnitude. The method was applied to the analysis of the
      biological reference materials (GBW 07602, bush branches and leaves; GBW 07604,
      poplar leaves), and the results obtained were in good agreement with the
      certified values.

PMID- 14658026
TI  - Size-related vaporisation and ionisation of laser-induced glass particles in the
      inductively coupled plasma.
AB  - Ongoing discussions about the origin of elemental fractionation occurring during
      LA-ICP-MS analysis show that this problem is still far from being well
      understood. It is becoming accepted that all three possible sources (ablation,
      transport, excitation) contribute to elemental fractionation. However,
      experimental data about the vaporisation size limit of different particles in the
      ICP, as produced in laser ablation, have not been available until now. This
      information should allow one to determine the signal contributing mass within the
      ICP and would further clarify demands on suitable laser ablation systems and gas
      atmospheres in terms of their particle size distribution. The results presented
      here show a vaporisation size limit of laser induced particles, which was found
      at particle sizes between 90 nm and 150 nm using an Elan 6000 ICP-MS. Due to the
      fact that the ICP-MS response was used as evaluation parameter, vaporisation and
      ionisation limits are not distinguishable. The upper limit was determined by
      successively removing the larger particles from the aerosol, which was created by
      ablation of a NIST 610 glass standard at a wavelength of 266 nm, using a recently
      developed particle separation device. Various particle fractions were separated
      from the aerosol entering the ICP. The decrease in signal intensity is not
      proportional to the decrease in volume, indicating that particles above 150 nm in
      diameter are not completely ionised in the ICP. Due to the limited removal range
      of the particle separation device, which cannot remove particles smaller than 150
      nm, single hole ablations were used to determine the lower vaporisation limit.
      This is based on measurements showing that larger particles occur dominantly
      during the first 100 laser pulses only. After this period, the ratio of ICP-MS
      counts and total particle volume was found to be constant while most of the
      particles are smaller than 90 nm, indicating complete vaporisation and ionisation
      of these particles. To describe the influence of different plasma forward powers
      on the vaporisation limit, the range 1000-1600 W was studied. Results indicate
      that optimum vaporisation and ionisation occurs at 1300 W. However, an increase
      of the particle ionisation limit towards larger particles was not observed within
      the accuracy of this study using the full range of parameters available for
      optimisation on commonly used ICP-MS instruments.

PMID- 14658025
TI  - Retinol-binding protein as a biomarker to assess endocrine-disrupting compounds
      in the environment.
AB  - Endocrine-disrupting compounds (EDC) are predominantly investigated with respect
      to their ability to mimic or block estrogenic actions. However, it is well-known
      that EDC can act as agonists or antagonists of androgen- and estrogen-response
      systems. For that reason, there is an obvious need for bioassays providing the
      possibility of detecting (anti-)estrogenic and (anti-)androgenic effects. The
      retinol-binding protein (RBP) seems to be a useful molecular biomarker for
      assessing all modes of action of EDC, because it is regulated by sex steroid
      hormones. This study was conducted to establish RBP as a biomarker for
      determination of (anti-)estrogenic and (anti-)androgenic effects of EDC using a
      Xenopus laevis primary hepatocyte culture system. It could be shown that RBP mRNA
      expression in X. laevis hepatocytes was stimulated by estrogens in a dose
      dependent manner whereas a combination of estrogen and androgen or estrogen and
      anti-estrogen treatment suppressed estrogenic stimulating effects. Androgens
      testosterone and dihydrotestosterone were able to reduce RBP mRNA expression and
      the anti-androgen vinclozolin could abolish the mRNA synthesis-suppressing
      activity of the androgen dihydrotestosterone. These results clearly demonstrated
      that RBP mRNA expression patterns in Xenopus laevis hepatocytes have different
      modes of (anti-)estrogenic and (anti-)androgenic action and can be used for
      examination of suspected EDC. Moreover, water samples from sewage-treatment plant
      effluents were applied to liver cells and expression levels of RBP and estrogen
      receptor mRNA (a known estrogenic biomarker) were detected. These samples had
      high estrogenicity but caused low to moderate induction of RBP mRNA synthesis,
      leading to the conclusion that RBP levels represent the sum of all possible
      effects (estrogenic and other effects) of EDC in environmental samples.

PMID- 14658027
TI  - Stripping chronopotentiometric measurements of lead(II) and cadmium(II) in soils
      extracts and wastewaters using a bismuth film screen-printed electrode assembly.
AB  - The key to remediative processes is the ability to measure toxic contaminants on
      site using simple and cheap sensing devices, which are field-portable and can
      facilitate more rapid decision-making. A three-electrode configuration system has
      been fabricated using low-cost screen-printing (thick-film) technology and this
      coupled with a portable electrochemical instrument has provided a a relatively
      inexpensive on-site detector for trace levels of toxic metals. The carbon surface
      of the screen-printed working electrode is used as a substrate for in situ
      deposition of a metallic film of bismuth, which allows the electrochemical
      preconcentration of metal ions. Lead and cadmium were simultaneously detected
      using stripping chronopotentiometry at the bismuth film electrode. Detection
      limits of 8 and 10 ppb were obtained for cadmium(II) and lead(II), respectively,
      for a deposition time of 120 s. The developed method was applied to the
      determination of lead and cadmium in soils extracts and wastewaters obtained from
      polluted sites. For comparison purposes, a mercury film electrode and ICP-MS were
      also used for validation.

PMID- 14658028
TI  - Controlled enzyme-immobilisation on capillaries for microreactors for peptide
      mapping.
AB  - In the present paper, the covalent immobilisation of the digesting enzyme trypsin
      has been achieved through photo-immobilisation on a portion of a silica
      capillary, thus leading to the construction of a capillary electrophoretic (CE)
      microreactor for peptide mapping. The CE-microreactor is characterised by being a
      single piece, thus ensuring no fluidic or electrical leakage. The enzyme was
      immobilised with a surface density of 15.8 microg/cm(2), the stability was high
      (80% after 38 days) and the rate of conversion was 0.2 ng/s. On-line protein
      mapping was tested with proteins of different dimensions, showing competitiveness
      in terms of time (completed map within 15 min) and exhaustive maps of small
      proteins. The results of the CE-microreactor and the potential to immobilise
      biocomponents easily on a desired portion of the capillary indicate further
      developments towards the construction of a variety of miniaturised enzymatic
      screening devices for high-throughput screening analysis.

PMID- 14658029
TI  - Cultures and languages: the worldview of science.

PMID- 14658030
TI  - Identification of N-glycosylation sites of the murine neural cell adhesion
      molecule NCAM by MALDI-TOF and MALDI-FTICR mass spectrometry.
AB  - Mass spectrometry has been shown in recent years to be a powerful tool to
      determine accurate molecular masses and sequences of peptides and proteins and
      post-translational modifications such as glycosylation, phosphorylation, and
      sulfation. For glycosylation, it has been increasingly recognized to be of
      pivotal importance to identify whether potential glycosylation sites are actually
      modified by glycans, because functions of proteins may be modulated or depend on
      the presence of glycans at specific sites. Several recent reports have
      established that mass spectrometric techniques such as matrix-assisted laser
      desorption/ionization or electrospray ionization mass spectrometry (MALDI-TOF or
      ESI-MS, respectively) with or without preceding HPLC and in combination with
      PNGase F treatment are suited to analyze whether consensus sequences for N
      glycosylation are glycosylated or not. Here we report the mass spectrometric
      analysis of the six potential N-glycosylation sites of the neural cell adhesion
      molecule NCAM from adult mouse brain. Unmodified peptides and glycopeptides each
      carrying a single glycosylation site were generated from NCAM by AspN and trypsin
      treatment and submitted to reversed-phase HPLC with or without prior enzymatic
      release of N-glycans. The resulting peptides were analyzed by MALDI-TOF-MS. In
      addition, high-resolution Fourier transform-ion cyclotron resonance (MALDI-FTICR)
      mass spectrometry was performed after in-gel deglycosylation and subsequent
      trypsin digestion. By using these procedures all six consensus sequences were
      shown to be glycosylated; the observation of an unmodified peptide with the
      consensus sequence N-1 indicates only partial glycosylation at this site.

PMID- 14658031
TI  - Luminescent enzyme-linked receptor assay for estrogenic compounds.
AB  - The analytics of endocrine-disrupting compounds has become a major issue during
      recent years. Several test systems have been developed for endocrine-disrupting
      chemicals. Yeast reporter gene assays and MCF-7 cell-based proliferation assays
      (E-screen) are particularly popular. A correlation of an enzyme-linked receptor
      assay (ELRA) with a yeast reporter gene assay is shown. In addition, the
      development of an ultra-sensitive luminescent ELRA with a detection limit of 20
      ng/L for 17 beta-estradiol in the sample is reported. Data for real sample
      analysis are shown in this paper. ELRA characteristics are compared with cell
      based assays, and the issue of detection limits is addressed. In this context,
      the detection limits of the cell-based assays have been claimed to be below the
      ELRA detection limits. However, it is clarified that the given detection limits
      for the yeast estrogen screen and the E-screen are usually based on
      concentrations of 17 beta-estradiol in the well, not in the sample, whereas ELRA
      detection limits are concentrations in the sample.

PMID- 14658032
TI  - Predictors of bone loss after hip fracture.
AB  - Although accelerated bone mineral density (BMD) loss follows hip fracture, little
      is known about factors associated with this loss. We examined potential
      predictors of BMD loss in a cohort of community-dwelling women who had sustained
      hip fracture and who were followed for 1 year after fracture. BMD was measured at
      the femoral neck, intertrochanteric region, and total body, during
      hospitalization and 2, 6, and 12 months later. Demographic, health, lifestyle,
      clinical, surgical, and functional characteristics at baseline, and postfracture
      activity were evaluated for associations with baseline BMD and BMD 1 year later.
      To examine possible BMD-dependent effects, high and low baseline BMD groups were
      defined. None of the studied factors consistently predicted either baseline BMD
      or BMD at 1 year after fracture, among women with either high or low baseline
      BMD. Baseline BMD was the only factor that substantially and consistently
      predicted change, explaining 70% to 90% of variation. These results suggest that
      BMD will not be preserved by general rehabilitative measures and that prompt,
      specific intervention to minimize bone loss after hip fracture is an essential
      element of clinical management of the hip fracture patient.

PMID- 14658035
TI  - Did the Chernobyl incident cause an increase in Type 1 diabetes mellitus
      incidence in children and adolescents?

PMID- 14658033
TI  - Is there any effect of suprascapular notch type in iatrogenic suprascapular nerve
      lesions? An anatomical study.
AB  - This anatomical study, which is aimed at assessing the effect of suprascapular
      notch type in iatrogenic suprascapular nerve lesions in surgical interventions,
      was conducted in two stages. A hundred dry scapulas and 20 scapulas of 11
      cadavera were classified according to Rengachary. The point of measurement was
      determined medially as the deepest point of suprascapular notch and laterally as
      supraglenoid tubercle in dry scapulas and anchor of biceps in cadavera. It was
      found that in the measurements made in dry scapulas, notch Type-IV scapulas,
      despite not being statistically significant, had the lowest average (2.35 cm),
      with minimum and maximum values of 2.1 cm and 2.78 cm respectively, when compared
      to other scapula types. It was found in the cadavera study that the measurements
      of one Type-IV scapula and one Type-V scapula were lower than the other types.
      Determination of the notch type in the rotator-cuff tears--especially in massive
      and retracted tears where supraspinatus has to be released from the fossa--may be
      helpful in avoiding iatrogenic nerve lesion.

PMID- 14658036
TI  - Posttraumatic epilepsy.

PMID- 14658037
TI  - Blood-brain barrier, hot water and seizures.

PMID- 14658038
TI  - Changes in blood-brain barrier permeability during hot water-induced seizures in
      rats.
AB  - Hot water epilepsy (HWE) was induced in freely moving Wistar rats by applying hot
      water jets over the head region. The status of the blood-brain barrier (BBB)
      during the seizures and during hot water-induced hyperthermia without seizures
      was examined using Evans blue dye. In order to investigate the contribution of
      concomitant factors to this process, synchronized body temperature and blood
      pressure recordings were also made. Tonic-clonic seizure activity was observed
      within an average of 3.9 min (SE= 0.6 min) in the rats exposed to the hot water
      jets; this treatment induced BBB opening in the cortical and deep brain areas.
      Body temperature and blood pressure increased from 36.5 degrees +/- 0.3 degrees C
      to 40.0 degrees+/- 0.2 degrees C, and from 91+/- 3 mmHg to 153+/- 4 mmHg,
      respectively. In the group of animals exposed to hot water application without
      inducing seizures, there were significant increases both in blood pressure and
      body temperature; however, the extravasation of Evans blue was not pronounced in
      the brains. Hot water-induced seizures, increased cerebrovascular permeability.
      Although high blood pressure and hyperthermia contribute to this permeability,
      the seizure activity is the major factor in this change.

PMID- 14658039
TI  - Assessing clinically relevant cognitive decline: preliminary data on a new
      method.
AB  - Physiological age-related cognitive decline, practice effect and regression to
      the mean may interfere with the interpretation of psychometric changes between
      subsequent neuropsychological evaluations. The standardized regression-based
      (SRB) change score allows investigators to define clinically relevant cognitive
      change on an individual basis controlling for these confounding factors. We
      performed a preliminary study to test its applicability and usefulness in the
      neuropsychological diagnosis of dementia. We derived a regression equation for
      the tests of a widely used Italian battery for global cognitive assessment, the
      Mental Deterioration Battery, in a sample of 20 normal elderly and we tested the
      potential clinical application of the SRB methodology in two cases of
      questionable dementia.

PMID- 14658040
TI  - Risk factors of multiple sclerosis: a case-control study.
AB  - We assessed the risk of multiple sclerosis (MS) associated with a series of
      putative risk factors. We studied 140 patients (90 women) with MS (mean age, 42.1
      years; SD= 10.2 years; disease duration, 10.9 years, SD= 7.5 years) and 131 sex
      and age-matched controls. Using a structured questionnaire, we collected
      information related to demographic data, socio-economic status, education,
      ethnicity, changes of domiciles, migration, occupation, environmental,
      nutritional and hormonal factors, exposure to various bacterial and viral agents,
      vaccinations, and family history of diseases. In multiple logistic regression
      analysis, we found independent risk factors of MS to be: familiarity for MS (OR=
      12.1; 95% CI, 1.3-110.7), autoimmune diseases (OR= 3.8; 95% CI, 2.0-7.1) and
      migraine (OR= 8.7; 95% CI, 1.0-75.4); comorbidity with autoimmune disease (OR=
      6.8; 95% CI, 1.4-32.0) and migraine (OR= 13.5; 95% CI, 1.5-116.6); and
      vaccination against measles (OR= 92.2; 95%, 12.1-700.2). Familial susceptibility
      to MS, autoimmune diseases and migraine, and vaccination to measles are
      associated with an increased risk of MS. The data collected in this study are
      confirmatory and support the hypothesis that etiology of MS constitutes the
      effect of interplay between genetic and environmental risk factors. However, the
      relatively small number of cases and controls prevents firm conclusions.

PMID- 14658041
TI  - Multiple sclerosis and exposure to organic solvents, investigated by genetic
      polymorphisms of the GSTM1 and CYP2D6 enzyme systems.
AB  - An association between multiple sclerosis (MS) and exposure to organic solvents
      has been discussed. Organic solvents are metabolised by enzyme systems like
      glutathione Stransferase M1 (GSTM1) and CYP2D6, which express polymorphisms in
      the general population. GSTM1 null genotype has been associated with solvent
      induced chronic toxic encephalopathy. Our aim was to see if a defect in one of
      these enzyme systems could explain the association between MS and exposure to
      organic solvents. In our study, 50 patients with MS were investigated, including
      24 who had been significantly exposed to organic solvents and 26 who were not
      exposed. Polymerase chain reaction-based methods were used for genotyping GSTM1
      and CYP2D6 polymorphisms in leukocyte DNA. No differences in genetic
      predisposition were found between MS patients exposed and those not exposed to
      organic solvents regarding GSTM1 null or CYP2D6 poor metaboliser genotypes. The
      possible association between multiple sclerosis and solvents may not, as for
      chronic toxic encephalopathy, be explained by defects in these systems.

PMID- 14658042
TI  - The alien hand syndrome: classification of forms reported and discussion of a new
      condition.
AB  - The term "alien hand" refers to a variety of clinical conditions whose common
      characteristic is the uncontrolled behavior or the feeling of strangeness of one
      extremity, most commonly the left hand. A common classification distinguishes
      between the posterior or sensory form of the alien hand, and the anterior or
      motor form of this condition. However, there are inconsistencies, such as the
      phenomenon of diagonistic dyspraxia, which is largely a motor syndrome despite
      being more frequently associated with posterior callosal lesions. We discuss
      critically the existing nomenclature and we also describe a case recently
      reported by us which does not fit any previously reported condition, termed
      agonistic dyspraxia. We propose that the cases of alien hand described in the
      literature can be classified into at least five broad categories: (i) diagonistic
      dyspraxia and related syndromes, (ii) alien hand, (iii) way-ward hand and related
      syndromes, (iv) supernumerary hands and (v) agonistic dyspraxia.

PMID- 14658043
TI  - Comparison of sensitivities of macro EMG and concentric needle EMG in L4
      radiculopathy.
AB  - The purpose of this study was to compare the sensitivities of macro EMG (mEMG)
      and concentric needle EMG (cnEMG) in showing abnormality in L4 radiculopathy. We
      evaluated 23 patients with clinically and radiologically proven L4 root lesions.
      Among these patients, 21 (92%) had cnEMG abnormalities. Out of 21 patients with
      cnEMG abnormality, 3 (14%) had fibrillations and positive sharp waves, 8 (38%)
      had interference pattern abnormality and all of them had motor unit potential
      (MUP) abnormality on quantitative MUP analysis. Seventeen patients (74%) had mEMG
      abnormality. Diagnostic yield of cnEMG is higher than mEMG in L4 radiculopathy.
      mEMG may not contribute much to the diagnosis of lumbar radiculopathy.

PMID- 14658044
TI  - How to calculate an MMSE score from a MODA score (and vice versa) in patients
      with Alzheimer's disease.
AB  - The aim of the present study was to provide a statistically sound way of
      reciprocally converting scores of the mini-mental state examination (MMSE) and
      the Milan overall dementia assessment (MODA). A consecutive series of 182
      patients with "probable" Alzheimer's disease patients was examined with both
      tests. MODA and MMSE scores proved to be highly correlated. A formula for
      converting MODA and MMSE scores was generated.

PMID- 14658045
TI  - Indriven sphenoid wing as a cause of post-traumatic epilepsy.
AB  - Post-traumatic epilepsy is more frequent after severe head injuries, however the
      severity of the trauma is not always correlated with the injured brain tissue. We
      report a patient whose seizures developed 4 years after a face trauma. Upward
      displacement of the sphenoid wing caused a contusion at the orbital surface of
      the frontal lobe. Computed tomography, magnetic resonance imaging and
      electroencephalographic findings are presented. The patient responded well to
      commonly used antiepileptic drugs.

PMID- 14658046
TI  - Venous thromboembolism in malignant glioma patients treated by chemoradiotherapy.

PMID- 14658047
TI  - Anti-annexin V antibodies in the cerebrospinal fluid and serum of patients with
      amyotrophic lateral sclerosis.

PMID- 14658048
TI  - Crossed aphasia with neglect.

PMID- 14658049
TI  - Markers of inflammation in cerebral ischemia.
AB  - The study sought to determine whether cerebral ischemia is associated with
      inflammatory reactions indicated by an increase in levels of selected acute phase
      proteins (APP), C-reactive protein (CRP), fibrinogen, alpha-1 antitrypsin (AAT)
      and acidic alpha-1 glycoprotein (AGP). These proteins are thought to be markers
      of inflammatory reactions. We investigated 30 patients with acute cerebrovascular
      ischemia, 20 patients with transient ischemic attack, and 20 patients from a
      control group. Levels of CRP, AAT, AGP, and fibrinogen in blood sera were
      determined in all patients by kinetic turbidimetry. In the patients with cerebral
      infarct an increase was found in the levels of APP, which suggests that ischemic
      necrosis is associated with inflammatory reactions. All patients require active
      treatment of an inflammatory process that is associated with stroke.

PMID- 14658050
TI  - Progression of preexisting trigeminalgia to Tolose-Hunt-like syndrome. The
      importance of neuroimaging for early differential diagnosis.
AB  - Recurrent unbearable, paroxysmal, unilateral facial pain in the distribution of
      one or more branches of the trigeminal nerve often provoked by sensory stimuli is
      typical for idiopathic trigeminal neuralgia. The less frequent localization in
      the area of ophthalmic branch (5%) is particularly controversial and should be
      distinguished from pathological lesions in the brainstem and middle and posterior
      cranial fossa and from diseases of the orbit and eye. This case study presents a
      79-year-old woman with typical clinical features of 1st division trigeminalgia
      without any neurological loss and with normal results of laryngological,
      ophthalmological, and stomatological examinations as well as neuroimaging CT, and
      MR /MRA evaluation. Only the evoked potential blink and masseter reflexes
      demonstrated the pathological values in the early phase of illness. After 1 year
      of pharmacological treatment no improvement was achieved and the pain became
      neuropathic and paresis of 3rd, 4th and 6th nerves developed, as observed in
      Tolose-Hunt syndrome. MRI of the orbit revealed a pathological mass in its apex
      with a connection to the superior orbital fissure. However, treatment with
      steroids was completely ineffective. Surgical resection of the tumor
      (leiomyosarcoma) only partially reversed oculomotor palsy and diminished aching.
      In differential diagnosis of idiopathic and symptomatic trigeminalgia, early MR
      and MRA imaging is the most essential and sometimes may be the best single test
      to evaluate lesions even in distant areas of the nervous system branches.

PMID- 14658051
TI  - Creatine kinase activity in amyotrophic lateral sclerosis patients.
AB  - The aim of this study was to investigate creatine kinase (CK) in the serum of
      amyotrophic lateral sclerosis (ALS) patients. Previous investigations have shown
      an increased CK activity in ALS patients and this has been suggested to be an
      indicator of patients survival. The study was conducted at the Department of
      Neurology, University School of Medicine in Lublin. Thirty ALS patients took part
      in the study. The average duration of the disease was 17 months. Serum CK levels
      were measured by the enzymatic method with N-acethylcysteine. CK was elevated in
      43.3% of the ALS patients. There were no significant differences in the serum CK
      level between the groups of the ALS patients depending on age, sex, duration of
      the disease, or clinical condition of patients. The CK level was significantly
      higher in the serum of the patients with a limb onset than in patients with a
      bulbar onset of ALS. Our study confirmed the increase in the serum CK activity in
      ALS patients. CK activity depends on a limb onset or a bulbar onset of ALS, but
      not on the duration of the disease and the severity of the clinical condition.

PMID- 14658052
TI  - Respiratory function in amyotrophic lateral sclerosis.
AB  - The aim of this study was to examine the vital capacity (FVC) and forced
      expiratory volume in 1 s (FEV 1) in relation to the site of amyotrophic lateral
      sclerosis (ALS) onset and the duration of the disease. Respiratory involvement is
      the principal cause of death in ALS patients. The study was conducted at the
      Department of Neurology, University School of Medicine in Lublin. The study
      comprised 18 ALS patients. The average duration of ALS was 12 months. The
      patients were divided into two groups according to the site of ALS onset and into
      two groups according to the duration of the disease. FVC was significantly higher
      in the group of patients with a limb onset than in the group of patients with a
      bulbar onset of the disease. The study has shown respiratory function
      disturbances in ALS patients. FVC significantly depends on the site of ALS onset
      but not on the duration of the disease.

PMID- 14658053
TI  - Effect of riluzole (Rilutek) treatment on plasma amino acid percentages in
      amyotrophic lateral sclerosis patients.
AB  - The aim of the study was to investigate the effect of riluzole (Rilutek)
      treatment on plasma amino acids (AA) percentage capacity in amyotrophic lateral
      sclerosis (ALS) patients. Excitatory AA may be important in the pathogenesis of
      ALS. Riluzole is a neuroprotective drug that blocks glutamatergic
      neurotransmission in the central nervous system. The study was conducted at the
      Department of Neurology, University School of Medicine in Lublin. The study
      comprised 20 ALS patients. Plasma AA were measured by automated ion-exchange
      chromatography before and after 3 months of riluzole treatment. The study has
      shown a significant decrease in serine percentage capacity and a significant
      increase in isoleucine percentage capacity in the plasma of the ALS patients,
      however the plasma excitatory AA percentage capacity was not significantly
      changed after 3 months of the riluzole treatment. Our investigations revealed
      that riluzole does not significantly influence the majority of plasma AA
      percentage capacity in ALS patients.

PMID- 14658054
TI  - Plasma amino acids percentages in amyotrophic lateral sclerosis patients.
AB  - The aim of the study was to examine plasma amino acids (AA) percentages in
      amyotrophic lateral sclerosis (ALS) patients. Altered metabolism of AA,
      especially excitatory AA in ALS, has been reported. The investigation was
      conducted at the Department of Neurology, University School of Medicine in
      Lublin. The study comprised 50 patients; 20 persons with ALS and 30 controls.
      Plasma AA were measured by automated ion-exchange chromatography. The results
      show significantly lower percentages of plasma tyrosine, valine, methionine,
      leucine, and isoleucine and significantly higher percentages of plasma glutamine
      and serine in ALS than in controls. The clinical state significantly influenced
      the percentage of plasma phenylalanine and alanine. Our study shows significant
      changes in some plasma AA percentages in ALS; however, excitatory AA percentages
      did not differ from the control subjects.

PMID- 14658055
TI  - Problems in diagnosing cranial base meningioma in patients with multiple
      sclerosis.
AB  - A 49-year-old patient had been suffering from the relapsing-remitting form of
      multiple sclerosis since the age of 23. Attacks of the disease appeared every 2
      years in the form of right-sided hemiparesis, vertigo, and problems in
      maintaining balance. The symptoms disappeared after treatment. At the age 32
      retrobulbar inflammation of the second cranial nerve appeared with visual acuity
      weakness. The symptoms disappeared after treatment. At the age of 42, bilateral
      weakness of visual acuity appeared and then epileptic attacks occurred. After
      surgical treatment of meningioma the symptoms disappeared. Only the features of a
      psycho-organic syndrome remained. The following attack of MS appeared 2 years
      after surgical intervention. MRI of the head disclosed numerous demyelinating
      foci.

PMID- 14658056
TI  - Hemiballismus following general anesthesia. A case report.
AB  - Hemiballismus is characterized by the abrupt onset of violent proximal flinging
      movements, affecting the limbs, neck and trunk on one side of the body. It is
      caused by the lesion in the region of the contralateral subthalamic nucleus of
      the Luys. Usually it is a self-limiting disease, lasting 6-8 weeks. A 49-year-old
      man has been admitted to the hospital after flinging movements of his right arm
      and the right side of the trunk occurred. A few days earlier he had undergone
      general anesthesia prior to a dental procedure. There was trouble in waking the
      patient afterwards. The movements lasted a few days. MRI of the brain revealed
      ischemic lesions areas in T2-weighted images localized in the region of globus
      pallidus bilaterally. EEG was abnormal, and showed slowed background activity
      with slow waves in left temporal lobe. He was treated with haloperidol,
      clonazepam and vasoactive medications. In spite of administered treatment,
      hemiballic movements reappeared occasionally. Due to increased frequency of the
      movements the patient was hospitalized again two years later. The second MRI
      revealed changes described earlier and a new ischaemic focus in left parietal
      lobe. Continuation of treatment with haloperidol was administered.

PMID- 14658057
TI  - Factors predicting early stroke fatality in Poland. Preliminary report of the
      Polish National Stroke Registry.
AB  - Poland has one of the highest rates of death due to stroke in Europe, which, in
      contrast to many industrialized countries, has not changed since at least 1984.
      To improve this unfavorable situation, the entire approach to stroke management
      needs to be recognized. For this purpose, an analysis of stroke epidemiology
      regarding regional differences was one of the the strategic points of the Polish
      National Project of Stroke Prevention and Treatment. The Polish National Stroke
      Registry was maintained from 1 January to 31 December 2000 in 59 Neurological
      Department in all 16 districts of Poland. In total 11,107 patients were included:
      11% with intracerebral hemorrhage, 63.4% with ischemic stroke, and 25.6% with
      unclassified stroke. Computed tomography (CT) was performed in 73.6% of patients.
      Analysis of in-hospital deaths showed great differences between the centers (from
      8% to 36%). According to multifactorial analysis, not only well-known predictors
      of early death (decrease in consciousness at the onset of stroke, decrease in
      functional state prior to stroke, and severity of stroke) influence the
      prognosis. In centers with high risk of death, CT, especially CT on admission,
      was performed significantly less often (4.2% vs. 62.6%), early rehabilitation was
      delayed (38.3% vs. 73.4%), and secondary prevention treatment was prescribed to
      fewer patients (antiplatelettherapy 36.4% vs. 77.4%; antithrombotic therapy 4.9%
      vs. 13%).

PMID- 14658058
TI  - The use of instrumental examinations in the diagnosis of headaches.
AB  - Headaches are the most common complaint reported by patients to their physician.
      They can be divided into spontaneous and symptomatic. The findings of the history
      and examination may suggest the need for diagnostic testing. The ancillary
      investigation and management of headache is discussed.

PMID- 14658059
TI  - New evidence of animal consciousness.
AB  - This paper reviews evidence that increases the probability that many animals
      experience at least simple levels of consciousness. First, the search for neural
      correlates of consciousness has not found any consciousness-producing structure
      or process that is limited to human brains. Second, appropriate responses to
      novel challenges for which the animal has not been prepared by genetic
      programming or previous experience provide suggestive evidence of animal
      consciousness because such versatility is most effectively organized by conscious
      thinking. For example, certain types of classical conditioning require awareness
      of the learned contingency in human subjects, suggesting comparable awareness in
      similarly conditioned animals. Other significant examples of versatile behavior
      suggestive of conscious thinking are scrub jays that exhibit all the objective
      attributes of episodic memory, evidence that monkeys sometimes know what they
      know, creative tool-making by crows, and recent interpretation of goal-directed
      behavior of rats as requiring simple nonreflexive consciousness. Third, animal
      communication often reports subjective experiences. Apes have demonstrated
      increased ability to use gestures or keyboard symbols to make requests and answer
      questions; and parrots have refined their ability to use the imitation of human
      words to ask for things they want and answer moderately complex questions. New
      data have demonstrated increased flexibility in the gestural communication of
      swarming honey bees that leads to vitally important group decisions as to which
      cavity a swarm should select as its new home. Although no single piece of
      evidence provides absolute proof of consciousness, this accumulation of strongly
      suggestive evidence increases significantly the likelihood that some animals
      experience at least simple conscious thoughts and feelings. The next challenge
      for cognitive ethologists is to investigate for particular animals the content of
      their awareness and what life is actually like, for them.

PMID- 14658060
TI  - Narrowing of the critical region in autosomal recessive spastic paraplegia linked
      to the SPG5 locus.
AB  - Hereditary spastic paraplegias are neurodegenerative disorders characterized
      clinically by progressive spasticity of the lower limbs. They are inherited as
      autosomal dominant, autosomal recessive, and X-linked traits. Four Italian
      families with autosomal recessive pure spastic paraplegia are reported. We show
      evidence of linkage to the SPG5 locus on chromosome 8p and our data reduce the
      candidate interval for SPG5 to the11-cM interval spanned by D8S285 and D8S544. We
      also report the search for mutations in five genes located in the region and
      their exclusion as candidates for SPG5.

PMID- 14658061
TI  - A predictive model for outcome after conservative decompression surgery for
      lumbar spinal stenosis.
AB  - This study was designed to develop predictive models for surgical outcome based
      on information available prior to lumbar stenosis surgery. Forty patients
      underwent decompressive laminarthrectomy. Preop and 1-year postop evaluation
      included Waddell's nonorganic signs, CT scan, Waddell disability index, Oswestry
      low back pain disability questionnaire, low back outcome score (LBOS), visual
      analog scale (VAS) for pain intensity, and trunk strength testing. Statistical
      comparisons of data used adjusted error rates within families of predictors.
      Mathematical models were developed to predict outcome success using stepwise
      logistic regression and decision-tree methodologies (chi-squared automatic
      interaction detection, or CHAID). Successful outcome was defined as improvement
      in at least three of four criteria: VAS, LBOS, and reductions in claudication and
      leg pain. Exact logistic regression analysis resulted in a three-predictor model.
      This model was more accurate in predicting unsuccessful outcome (negative
      predictive value 75.0%) than in successful outcome (positive predictive value
      69.6%). A CHAID model correctly classified 90.1% of successful outcomes (positive
      predictive value 85.7%, negative predictive value 100%). The use of conservative
      surgical decompression for lumbar stenosis can be recommended, as it demonstrated
      a success rate similar to that of more invasive techniques. Given its physiologic
      and biomechanical advantages, it can be recommended as the surgical method of
      choice in this indication. Underlying subclinical vascular factors may be
      involved in the complaints of spinal stenosis patients. Those factors should be
      investigated more thoroughly, as they may account for some of the failures of
      surgical relief. The CHAID decision tree appears to be a novel and useful tool
      for predicting the results of spinal stenosis surgery

PMID- 14658062
TI  - Homocysteine and left ventricular hypertrophy in children with chronic renal
      failure.
AB  - Hyperhomocysteinemia is recognized as an independent risk factor for
      cardiovascular disease, especially atherosclerosis, in adult patients with
      chronic renal failure (CRF). However, there is little information about the
      relationship between plasma homocysteine levels and left ventricular hypertrophy.
      The aim of this study was to determine plasma homocysteine levels and risk
      factors for left ventricular hypertrophy and to investigate the relationship
      between plasma homocysteine concentration and left ventricular mass index (LVMI)
      in children with CRF. The homocysteine level was measured by high-performance
      liquid chromatography and LVMI was calculated using echocardiographic findings in
      27 children with CRF and 16 healthy controls. The mean LVMI and mean plasma
      homocysteine concentration in the CRF group, especially in patients with end
      stage renal disease, were statistically higher than the control group ( P<0.05).
      There was no correlation between LVMI and plasma homocysteine concentration.
      There was a positive correlation between plasma homocysteine concentration and
      serum creatinine level. There was a positive correlation of LVMI with creatinine
      and blood pressures (systolic, diastolic, and mean arterial pressure). There was
      a negative correlation of LVMI with hemoglobin level in multiple linear
      regression analysis. In our view homocysteine does not have a direct effect on
      left ventricular structure and left ventricular hypertrophy is the end organ
      damage associated with hypertension, anemia, and CRF. More prospective studies
      are needed to better clarify the inter-relationships of plasma homocysteine level
      and left ventricular structure in children with CRF.

PMID- 14658064
TI  - Immunoglobulin protein and gene transcripts in ovarian follicles throughout
      oogenesis in the teleost Dicentrarchus labrax.
AB  - Transfer of immunoglobulins (IgM-like) from the female to the teleost embryo has
      been demonstrated but mechanisms of uptake into and storage within the eggs
      remain to be clarified. The monoclonal antibody DLIg3 against Dicentrarchus
      labrax Ig light chain revealed an active role of both follicle cells and oocytes
      in the Ig uptake. The primordial follicular cells showed DLIg3 immunoreactivity
      even at a pre-vitellogenetic stage. Early vitellogenetic oocytes (lipid vesicle
      stages) had DLIg3 staining of pore canals, plasmalemma and outer cortex and of
      their follicular cells. In protein yolk granule oocytes, DLIg3 staining was also
      detected within vesicles of the outer-mid cortex and juxtanuclear yolk granules;
      therefore, a centripetal transport of Ig throughout oocyte development is
      apparently carried out. Immunoelectron microscopy confirmed the presence of Ig
      within thecal and granulosa cells (and in the interposed basement membrane) of
      pre-vitellogenic and vitellogenic follicles. Thus, the transport of Ig to the egg
      apparently occurs also by transcytosis across the follicle cells. Igs were
      localised in the pore canals surrounding the microvilli and in vesicles of outer
      mid cortex of vitellogenic oocytes. Reverse transcription/polymerase chain
      reaction with primers designed for the constant region of sea bass Ig light chain
      detected Ig mRNA in hydrated oocytes, a smaller content in released eggs and no
      signal in larvae at day two post-hatching. These findings show that a significant
      level of Ig gene transcription in the oocyte and/or a transfer of transcripts may
      also occur.

PMID- 14658065
TI  - Protein-losing gastroenteropathy and retinitis associated with cytomegalovirus
      infection in an immunocompetent infant: a case report.
AB  - A 6-week-old immunocompetent girl developed protein-losing gastroenteropathy
      (PLGE) and retinitis associated with cytomegalovirus (CMV) infection. At
      presentation, CMV antigenaemia (6 cells/46,000 white blood cells) and its DNA
      were detected in the patient's blood and in the mother's milk. Intravenous
      ganciclovir and gamma-globulin rapidly ameliorated all symptoms and CMV
      antigenaemia disappeared. No immunological defects were identified in this
      patient. To the best of our knowledge, this case involves the youngest known
      immunocompetent patient demonstrating CMV-induced PLGE and retinitis. CONCLUSION:
      breast-feeding by a cytomegalovirus-positive mother can be a primary cause of
      early onset cytomegalovirus infection in infants.

PMID- 14658066
TI  - Endoscopic laser posterior cordectomy in a newborn with bilateral vocal fold
      paralysis and cerebro-oculo-facio-skeletal (Pena-Shokeir II) syndrome.

PMID- 14658067
TI  - Real-time observation of autophagic programmed cell death of Drosophila salivary
      glands in vitro.
AB  - Autophagy, a form of programmed cell death (PCD) that is morphologically
      distinguished from apoptosis, is thought to be as prevalent as apoptosis, at
      least during development. In insect metamorphosis, the steroid hormone 20
      hydroxyecdysone (ecdysone) activates autophagic PCD to eliminate larval
      structures that are no longer needed. However, in comparison with apoptosis,
      there are not many studies on the regulation mechanisms of autophagy. To provide
      a useful model for studying autophagic PCD, I established an in vitro culture
      system that enables real-time observation of the autophagic cell destruction of
      Drosophila salivary glands. The new system revealed that de novo gene expression
      was still required for the destruction of salivary glands dissected from
      phanerocephalic pupae. This indicates the usefulness of the system for exploring
      genes that participate in the last processes of autophagic PCD.

PMID- 14658068
TI  - Immunogenicity of parathyroid allografts in the rat: immunosuppressive dosages
      effective in passenger leukocyte-rich small bowel transplants are not effective
      in parathyroid gland transplants with few passenger leukocytes.
AB  - BACKGROUND AND AIMS: The passenger leukocytes harboured within an allograft
      induce a massive allo-immune response that leads to allograft rejection if not
      countered by immunosuppression. We compared the response to short-term
      immunosuppression of parathyroid gland transplants possessing few passenger
      leukocytes with that of passenger leukocyte-rich small bowel transplants.
      METHODS: Heterotopic parathyroid and orthotopic small bowel transplantation was
      performed in a Wistar Furth-to-Lewis rat strain combination. Immunosuppression
      with cyclosporine A (CsA) was administered in different dosages for 14 days.
      Dysfunctional allografts were examined immunohistologically. RESULTS: CsA more
      effectively suppressed the immune response provoked by immunogenic small bowel
      grafts than that induced by less-immunogenic parathyroid grafts.
      Immunosuppression with 20 mg/kg per day induced long-term survival in the small
      bowel (165+/-21 days) but not in the parathyroid (28+/-3 days). All rejected
      grafts featured massive cellular infiltration by activated T cells as a sign of
      immune rejection. CONCLUSION: Immunosuppressive dosages effective in passenger
      leukocyte-rich small bowel transplants were not as effective in parathyroid gland
      transplants harbouring few passenger leukocytes. In spite of the paucity of
      passenger leukocytes in parathyroid grafts it is more difficult to control by
      immunosuppression the immune response to them than that to the passenger
      leukocyte-rich small bowel.

PMID- 14658069
TI  - Effect of chronic exposure to methylmercury on eye movements in Cree subjects.
AB  - OBJECTIVES: To examine the effect of chronic exposure to methylmercury on eye
      movements (pursuit, fixation and dynamic saccades) in Cree subjects from Northern
      Quebec. METHODS: Eye movements were recorded in a group of Cree subjects ( n=36)
      exposed chronically to methylmercury, a group of patients with Parkinson's
      disease (PD) ( n=21), and a group of control subjects ( n=30) by use of an
      infrared eye-movement recording system. Pursuit, fixation, and prompted and
      remembered saccades were recorded twice for both eyes in the horizontal and
      vertical axes. Blinks were removed, and data were calibrated. RESULTS: Analyses
      of variance revealed significant differences for all characteristics examined for
      fixation and pursuit, and for some characteristics in dynamic saccades. These
      differences arose sometimes from the Cree group, sometimes from the PD group and
      sometimes from both groups. CONCLUSIONS: The results suggest that eye movements
      of Cree subjects exposed to methylmercury are qualitatively different from those
      of both control subjects and patients with PD. Comparisons between more-exposed
      and less-exposed Cree subjects matched for age with control subjects also showed
      significant differences for fixation, pursuit and dynamic saccades. The average
      scores of the more-exposed group were clearly separated from those of the less
      exposed and control groups for characteristics of fixation and pursuit, and for
      accuracy and sharpness of prompted saccades. This trend was less clear in other
      results where a possible effect of mercury exposure could not be distinguished
      from a possible cultural effect. Further studies should focus on the most
      discriminating characteristics for the Cree group, such as measures of accuracy
      and coherence in all tests and sharpness of saccades.

PMID- 14658070
TI  - Protein kinases expressed by interstitial cells of Cajal.
AB  - Interstitial cells of Cajal (ICC) are involved in the generation of electrical
      rhythmicity of intestinal muscle and in the transduction of neural inputs in the
      gut. Although the expression of receptors for neurotransmitters and hormones and
      some second messengers have been investigated in ICC, the protein kinases present
      in these cells have not been well documented. This study has demonstrated the
      immunohistochemical localisation of PKA, PKC gamma and PKC theta in ICC that were
      identified by the known ICC marker, c-Kit, in the guinea-pig gut. Other PKCs, PKC
      alpha, beta, delta, epsilon, eta, iota and lambda, and Ca(2+)-calmodulin
      dependent protein kinase II were not localised in ICC. Double labelling studies
      were conducted on longitudinal muscle-myenteric plexus and external muscle
      myenteric plexus preparations of the oesophagus, stomach (fundus, corpus and
      antrum), duodenum, distal ileum, caecum, proximal and distal colon, and rectum.
      The three protein kinases were detected in c-Kit-immunoreactive ICC at the level
      of the myenteric plexus (IC-MY), in the muscle (IC-IM) and at the level of the
      deep muscular plexus (IC-DMP) in the small intestine. PKA was found in over 90%
      of IC-IM in all regions examined, and in over 90% of IC-MY in the gastric body
      and antrum and throughout the small and large intestines. PKC gamma was in the
      majority of ICC in the gastric body and antrum and in the small intestine, but
      was largely absent from ICC in the oesophagus, proximal stomach and large
      intestine. PKC theta occurred in the majority of ICC in all regions except the
      rectum. The intensity of staining was greatest for PKA, with PKC gamma giving
      comparatively weak labelling of ICC. PKA was also detected in myenteric neurons,
      smooth muscle, macrophages and fibroblast-like cells. PKC gamma labelling
      occurred in large, multipolar neurons throughout the small and large intestine,
      as well as in lymph vessels and in capillaries. It is concluded that PKA, PKC
      gamma and PKC theta are all present in ICC, with the differences in their
      localisations suggesting specific roles for each in ICC function.

PMID- 14658071
TI  - Protection by iodide of lens from selenite-induced cataract.
AB  - BACKGROUND: Iodide has been used empirically against different age-related eye
      diseases, including cataract. The purpose of the present study was to investigate
      the effect of iodide on selenite-induced cataract in rat lens. METHODS: Young
      white rats received subcutaneously sodium selenite (20 and 30 nmol/g b.w.) on day
      13 post partum (p.p.). Cataract development was measured by expert estimation and
      image data analysis. Potassium iodide (1.5 nmol/g b.w.) was given (1-5 times)
      i.p. at different times with respect to the selenite administration. Lens
      opacification was analyzed in selenite, selenite-iodide, iodide and control
      groups on day 7 after selenite administration. RESULTS: Iodide showed a
      significant protective effect against selenite cataract when injected 2 days (2
      times) before selenite injection, i.e., on days 11 and 12 p.p. No significant
      effects on lens opacity were found: (1) after only one iodide injection (on day
      12 p.p.), (2) after an initial iodide administration 1 h before selenite and (3)
      after injections of iodide once a day for 5 consecutive days. The protective
      effect of iodide was the same (about 50%) for both selenite doses used.
      CONCLUSIONS: There is a time-dependent protective influence of iodide against
      selenite cataract development. It is supposed that the anticataract effect of
      iodide could be based on direct or indirect antioxidant mechanisms.

PMID- 14658072
TI  - Evaluation of the blood-aqueous barrier by laser flare cell photometry following
      retinal cryocoagulation.
AB  - PURPOSE: To evaluate the influence of peripheral 360 degrees retinal
      cryocoagulation on the blood-aqueous barrier of patients with retinal vascular
      disorders. METHODS: The aqueous of 50 eyes of 50 patients with diabetic
      retinopathy or central vein occlusion was measured by laser flare photometry (FC
      2000, Kowa) before peripheral 360 degrees retinal cryocoagulation and 1 day, 1
      week, and 1 month thereafter. RESULTS: Mean aqueous flare values before treatment
      were 15.7 (+/-8.2) photon counts/ms; mean cell count was 9.8 (+/-14.8) cells/0.5
      mm(3). One day after retinal cryocoagulation flare values had increased
      statistically significantly to a mean of 39.2 (+/-85.8) photon counts/ms, while
      the increase in mean cell number to 15.0 (+/-37.2) cells/0.5 mm(3) did not reach
      statistical significance. One week following treatment, mean flare values had
      dropped to 30.9 (+/-49.6) photon counts/ms and were no longer significantly
      elevated compared with baseline, while the mean cell count of 11.1 (+/-27.0)
      cells/0.5 mm(3) was now statistically significantly elevated compared with
      baseline. One month after treatment the flare values had decreased to a mean of
      19.7 (+/-12.0) photon counts/ms, and mean cell count had decreased to 8.1 (+/
      10.4) cells/0.5 mm(3); at this point neither parameter showed a statistically
      significant difference from baseline values. CONCLUSION: Peripheral 360 degrees
      retinocryocoagulation does not lead to permanent disturbance of the blood-aqueous
      barrier.

PMID- 14658073
TI  - RPE cell cultivation.

PMID- 14658074
TI  - Acute arterial occlusion after total knee arthroplasty.
AB  - The duration of the ischemic time in total knee arthroplasty is currently
      considered to be an important predictor for the development of arterial
      thrombosis. In the following, we describe two patients with thrombotic occlusions
      of the popliteal artery. After the first one had been operated on under ischemic
      conditions, the ischemic time was limited to the cementing phase in the second
      case on the basis of this experience, but an arterial occlusion occurred in this
      case as well. In neither case did immediate vascular surgery lead to clinical
      restrictions. Our observation demonstrates that arterial thromboses can occur
      regardless of the duration of ischemia and that surgery should therefore be
      performed without ischemia if risk factors are present.

PMID- 14658075
TI  - Limited posterior approach for internal fixation of a glenoid fracture.
AB  - We present the case of a patient who was treated by open reduction and internal
      fixation for a displaced glenoid fracture using a limited posterior approach.

PMID- 14658077
TI  - Progressive collapse of transposed necrotic area after transtrochanteric
      rotational osteotomy for osteonecrosis of the femoral head induces osteoarthritic
      change. Mid-term results of transtrochanteric rotational osteotomy for
      osteonecrosis of the femoral head.
AB  - INTRODUCTION: Osteonecrosis of the femoral head is usually progressive, and once
      collapse of the femoral head develops, joint destruction almost invariably
      follows. Therefore, for partial osteonecrosis of the femoral head, various types
      of osteotomies have been developed in an attempt to save the femoral head and
      maintain the natural function of the hip joint. MATERIALS AND METHODS: We
      reviewed 25 hips in 21 patients for a mean follow-up period of 6.4 years after
      Sugioka's transtrochanteric anterior rotational osteotomy for osteonecrosis of
      the femoral head. RESULTS: The clinical results were excellent or good in 20 hips
      (80%), and radiological success was observed in 15 hips (60%) with an absence of
      both collapse of the newly established weight-bearing area of the femoral head
      and narrowing of the joint space. Progressive collapse of the transposed necrotic
      area was noted in 10 hips (40%), and of these 10 hips, narrowing of the joint
      space was observed in 7 (70%) at follow-up. A significant correlation was
      demonstrated between progressive collapse of the transposed necrotic area and
      narrowing of the joint space. Growth of an osteophyte of the femoral head was
      observed postoperatively in 16 hips (64%), particularly at anterior and lateral
      sites of the femoral head. CONCLUSIONS: Though collapse of a new weight-bearing
      area can be prevented, progressive collapse of the transposed necrotic area
      induces anterior joint instability, giving rise to osteoarthritic change. It is
      therefore concluded that prevention of the collapse of the transposed necrotic
      area is important for satisfactory long-term results.

PMID- 14658078
TI  - [About quality of diagnostic ultrasound - an enduring problem between reality and
      satire].

PMID- 14658079
TI  - Observational studies on ultrasound screening for developmental dysplasia of the
      hip in newborns - a systematic review.
AB  - AIM: To assess whether observational studies provide evidence to support general
      ultrasound screening for developmental dysplasia of the hip (DDH). METHOD:
      Systematic Review. Following a predefined study protocol, observational studies
      on ultrasound screening in unselected newborns were identified by search through
      23 electronic databases and by hand search. Two reviewers selected the studies
      independently of each other and extracted the data. RESULTS: 49 observational
      studies were included. The prevalence of DDH ranged from 0.5 % to 30 % depending
      largely on the various possible definitions of DDH. Less than 0.1 % of patients
      with DDH were missed by ultrasound regardless of the technique employed (Graf or
      Terjesen). About 90 % of newborns with Graf type IIa hips requiring ultrasound
      control did not develop DDH. Only six studies with 23 108 newborns reported on
      complications, and there was only one infant with an avascular necrosis of the
      femoral head. The effectiveness of a general ultrasound screening cannot be
      evaluated reliably for several reasons: reports were often incomplete, follow-up
      of newborns with normal findings at the time of screening was often not carried
      out, clinically meaningful data about outcome as well as control groups were
      missing. CONCLUSION: General ultrasound screening for developmental dysplasia of
      the hip cannot be sufficiently assessed by the observational studies available.
      The lack of evidence does not mean that ultrasound screening is ineffective, but
      randomized controlled trials comparing the effectiveness of different screening
      regimens are needed.

PMID- 14658080
TI  - [Transabdominal ultrasonography in the diagnosis of lumbar disc herniation].
AB  - AIM: The aim of our study was to assess the value of transabdominal
      ultrasonography in the diagnosis of a lumbar herniated disc and to investigate
      the influence of the quality of the ultrasonography investigation on detection of
      pathological changes in lumbar intervertebral disc. METHOD: 119 patients (55
      female, 64 male, mean age 41 years) were included in our study. Patients were
      suffering from lower back pain and were investigated by transabdominal
      ultrasonography, using a 3.5 MHz scanner. The results of the ultrasonography
      investigation were compared with MRI and intraoperative findings RESULTS: The
      quality of the ultrasonography documentation shows distinct differences between
      the segments of the lower lumbar spine (L3/4 86.6 %, L4/5 85.7 %, L5/S1 70.6 %).
      The sonographic evaluations were correct in 75.4 % of cases. Sensitivity of
      ultrasonography for the detection of an intradiscal lesion was 0.46 for L3/4,
      0.83 for L4/5 and 0.78 for L5/S1. Specificity was 0.91 for L3/4, 0.65 for L4/5
      and 0.67 for L5/S1. CONCLUSION: Compared to MRI investigation transabdominal
      ultrasonography of the lumbar herniated disc proved to be distinctly inferior
      because of methodical limitations and lower diagnostic accuracy. This method,
      however, can be used as a preliminary diagnostic procedure.

PMID- 14658081
TI  - [Ultrasonographic evaluation of the rotator cuff after shoulder arthroplasty].
AB  - AIM: Ultrasonography of the rotator cuff tendons is a standard imaging technique.
      Although increasing numbers of shoulder arthroplasty are performed, there is no
      available data concerning the use of ultrasound after shoulder replacement. Our
      experimental study was performed to analyse the value of ultrasonography after
      shoulder arthroplasty a) in an ex-vivo-setting and b) in a retrospective analysis
      of our patients after shoulder hemiprothesis. METHOD: After defrosting, anatomic
      modular humeral head replacement was performed in four fresh-frozen specimens
      with intact rotator cuffs. The supraspinatus and subscapularis tendons of each
      specimen were either detached to simulate a cuff defect or reattached
      anatomically (four times per specimen). Two experienced examiners then performed
      ultrasonography to evaluate the two tendons to be either intact or deficient. In
      a retrospective study, 22 patients with 25 hemiprotheses of the shoulder
      underwent clinical and sonographic examination. For documentation of the clinical
      findings, the Constant score was used. RESULTS: In the cadaver study, the
      reliability of the method was slightly higher for the subscapularis tendon (13
      correct, 3 false results) than for the supraspinatus tendon (12 correct, 4 false
      results). In our patients, rotator cuff defects and effusions around the biceps
      tendon and in the subdeltoid bursa could be detected. Normal sonograms correlated
      with good clinical results. CONCLUSION: In the cadaver study, we found a good
      reproducibility of in-vivo conditions. We believe that ultrasonography is
      beneficial in follow-up evaluation after shoulder arthroplasty.

PMID- 14658082
TI  - [Sonographically guided percutaneous needle aspiration of breast abscesses - a
      minimal-invasive alternative to surgical incision].
AB  - AIM: The current standard treatment of breast abscesses is surgical incision and
      drainage. This method, however, frequently yields poor cosmetic results.
      Sonographically guided percutaneous aspiration of breast abscesses and local
      antibiotic treatment need to be considered as an interesting alternative. The
      present study aimed to compare these treatment alternatives. METHOD: The patient
      population analysed comprised 24 patients with 28 breast abscesses who presented
      to the Department of Obstetrics and Gynaecology of Munich University Hospital
      Grosshadern between 12/1997 and 9/2002. 25 % of these patients (6/24) suffered
      from a puerperal and 75 % (18/24) from a non-puerperal breast abscess. The study
      group of surgically treated patients comprised 15 women (16 abscesses). Ten
      patients (10 abscesses) were treated with the novel, minimally invasive method.
      The treatment success was statistically analysed using chi (2)- and t-Tests (p <
      0,05). RESULTS: The minimally invasive approach did not extend the length of
      intravenous antibiotic treatment or hospital stay and did not lead to an increase
      in the need for analgesic drugs. We encountered recurrent abscesses in 31 %
      (5/16) of the surgical treatment group, yet none in the group undergoing
      minimally invasive treatment. The aesthetic-cosmetic as well as the functional
      result in lactating patients was satisfactory in all cases. CONCLUSION:
      Sonographically guided percutaneous aspiration of breast abscesses represents a
      less invasive and very promising alternative to surgical incision, showing the
      following advantages: no general anaesthesia required, a superior cosmetic result
      and shorter hospitalisation. The method was highly accepted by all patients
      treated.

PMID- 14658083
TI  - [Intraoperative ultrasound of intra- and extramedullary tumours].
AB  - AIM: Spinal tumours can be diagnosed precisely by magnetic resonance imaging
      (MRI). Planning the surgical procedure of intradural tumours, intraoperative
      ultrasound (IOUS) has been used to evaluate its diagnostic potential. METHOD:
      From 1997 to 9/2002 32 patients with the diagnosis of an ependymoma (n = 9),
      astrocytoma (n = 5), haemangioblastoma (n = 5), neurinoma (n = 4), meningeoma (n
      = 4) and filum terminale ependymoma (n = 5) were investigated by intraoperative
      transdural sonography. The sonographic results were correlated to the
      preoperative MRI-findings and histopathological work-up. RESULTS: Intramedullary
      tumours characteristically present with a heterogenous morphology, sometimes
      carrying intralesional or perilesional cysts. The tumour margins are frequently
      poorly defined, and there is a perifocal oedema. Extramedullary tumours
      frequently display a homogenous signal intensity, well defined tumour margins and
      the abscence of perifocal oedema. Haemangioblastomas turned out to be a specific
      sonographic entity among intramedullary tumours, as they most often contain only
      a cystic part with a small tumour nodule. IOUS influenced the surgical approach
      as laminotomy has to be extended in 7/32 cases to reach the tips of the tumour.
      CONCLUSION: The precision of surgical exposure of intradural spinal lesions can
      be optimised by IOUS which shows a high correlation with MRI characterizing extra
      and intramedullary tumours. Using IOUS, the exact position of the
      laminectomy/laminotomy can be adapted to the true extent of the tumour, thus
      avoiding the necessity of further bone work in the case of the frequently
      oedematous spinal cord protruding through the opening in the dura. Overall, IOUS
      guidance can help to reduce postoperative morbidity in surgery for all spinal
      intradural lesions.

PMID- 14658084
TI  - Prenatal diagnosis of a giant foetal lymphangioma and haemangiolymphoma in the
      second trimester using 2D and 3D ultrasound.
AB  - Lymphangiomas are benign tumours of the lymphatic system. Early prenatal
      diagnosis is important to permit a planned delivery and provide adequate
      postnatal care. It thereby improves prognosis and allows the option of
      terminating the pregnancy if poor outcome is predicted. We report two cases, a
      giant haemangiolymphoma and a lymphangioma. 2D and 3D US findings are presented
      and differential diagnosis, therapeutic options and prognosis are discussed.

PMID- 14658085
TI  - ["Disappearance" of retroperitoneal vessels - a case report].
AB  - We report the ultrasound findings in a case of pneumo-retroperitoneum. The 74
      year-old patient was admitted because of severe dyspnoea. Chest X-ray revealed a
      left-sided pleural effusion, and a drainage was performed. Later on the patient
      for the first time complained about severe pain in the lower abdomen. Ultrasound
      of the abdomen was performed. Sonographically, it was remarkably difficult to
      obtain images of the right kidney and the retroperitoneal vessels, as massive
      reverberation artifacts in the retroperitoneum were present. Plain radiography of
      the abdomen revealed free retroperitoneal and intraabdominal gas. At laparotomy a
      perforated diverticulitis of the sigma was discovered. Postoperative follow-up
      was uneventful, but the recurrent pleural effusion was later confirmed to be due
      to a malignant mesothelioma. This article discusses the characteristic
      sonomorphologic features of pneumo-retroperitoneum and its differential
      diagnosis. Although free retroperitoneal air is a rare condition, it is crucial
      for the examiner to be aware of the characteristic sonographic findings in order
      to initiate appropriate therapy.

PMID- 14658086
TI  - [Giant haemangioma of the liver - clinical and diagnostic problems - a case
      report].
AB  - Typical echodense haemangiomas of the liver can easily be identified by B-scan
      ultrasound. Atypical or giant haemangiomas of the liver, however, need to be
      differentiated from secondary tumours or primary liver carcinomas and
      cholangiocarcinomas. Until recently, computed tomography or magnetic resonance
      tomography were required to confirm the diagnosis, and not so rarely even a
      fairly risky fine-needle puncture had to be performed. Contrast media-assisted
      sonography, in general, offers the same scope of differentiating liver tumours as
      the radiographic tomography methods. Contrast media-assisted sonography is not
      yet widely available and has not been sufficiently evaluated. One important
      limitation is thought to be the lack of echo depth. We demonstrate the diagnostic
      value of this method in the case of a liver haemangioma measuring more than 20 cm
      in diameter. The resulting clinical questions are being discussed.

PMID- 14658087
TI  - [Sonographic measurement of endometrium thickness as a predictive value for
      pregnancy through IVF].

PMID- 14658090
TI  - [Psychiatrische Praxis: 30th anniversary].

PMID- 14658091
TI  - [German-speaking mental health services research - what and how is reported? An
      analysis of publishing in Psychiatrische Praxis 1999-2002].
AB  - OBJECTIVE: In mental health service research, the investigated services and care
      systems as well as the research methodology should be described in a precise and
      transparent fashion so that findings can be clearly interpreted and used.
      Therefore, this study investigates what is reported in German language
      publications on mental health service research. METHOD: All original papers on
      mental health service research, that were published in the Psychiatrische Praxis
      between 1999 and 2002, were systematically reviewed and, using a structured
      classification system, subjected to content analysis. In particular, it was
      assessed what forms of care had been studied and what characteristics of care
      were reported. RESULTS: 54 % (199) of all original publications reported mental
      health service research in a wide sense. Of these, 8 % were qualitative studies.
      58 % of studies investigated in-patient treatment, 20 % comprehensive care
      systems, and 4 % services provided by psychiatrists or psychotherapists in
      private office practice. There were hardly any studies on innovative service
      models. In 51 % of studies, authors had conducted investigations within their own
      service or care system. In most articles characteristics of the patient sample
      were exactly described, whilst precise information on the researched service,
      such as funding, staffing and organisation, was usually missing. DISCUSSION:
      There still is relatively little research on outpatient services, and mental
      health service research is not yet appropriately based in the community.
      Requirements for exact and comprehensive descriptions of the researched services'
      and care systems are rarely met. In general, the findings suggest that mental
      health service research in German speaking countries might benefit from studies
      with researchers who are independent from the investigated service, the
      evaluation of innovative service models, and above all a standardised description
      of the services and context in research studies.

PMID- 14658092
TI  - [Current topics of social-psychiatric research in German speaking countries: a
      content analysis of scientific journals].
AB  - AIM: The paper is aimed at investigating what the actual topics of social
      psychiatric research in German speaking countries are. METHOD: German and
      international journals covering psychiatry and adjacent disciplines were screened
      for articles dealing with social-psychiatric topics. All in all, 426 relevant
      articles were identified and subjected to a content analysis. RESULT: Almost one
      third of all articles was dealing with research on mental health services.
      Another research area that was strongly represented was epidemiology. By
      contrast, articles devoted to the study of psycho-social causes of mental
      disorders and psycho-social determinants of its course were rather rare.
      DISCUSSION: Possible reasons for the observed trends in social-psychiatric
      research are discussed. Potential risks for social psychiatry resulting from a
      too one-sided emphasis on health service research are pointed out.

PMID- 14658093
TI  - [Madhouse, asylum, retreat, specialist hospital - on the genesis and history of
      names for psychiatric institutions in Germany until the beginning of the 20th
      century].
AB  - This paper analyses the history of names for psychiatric institutions in the
      German language. When scientific, medical psychiatry came into being in the late
      18 (th) century, names with negative connotations such as "Narrenhaus" or
      "Tollhaus" (approximating to the English word "madhouse") were substituted by the
      then neutral "Irrenhaus" and later in the 19 (th) century by "Irrenanstalt".
      Soon, however, this new term became associated with negative connotations, making
      it unsuitable as a reflection of the many improvements made both in the treatment
      and the public image of psychiatric service users. Changes in word form such as
      "Heilanstalt", "Pflegeanstalt" and "Heil- und Pflegeanstalt" better reflect the
      character of the institutions. Objections to the word "Anstalt" (institution)
      were not acknowledged until the 20 (th) century when the term "Fachkrankenhaus"
      ("specialist hospital") was introduced. Before then the German word "Klinik" was
      reserved for university hospitals, the first of which was founded in 1878. The
      history of names for psychiatric institutions reflects both changes in the
      treatment of the mentally ill and the attempts made above all by psychiatrists to
      face and overcome stigmatisation of their clients.

PMID- 14658094
TI  - [Voting behaviour of the chronic mentally ill].
AB  - OBJECTIVE: Voting behaviour of chronic mentally ill patients should demonstrate
      that this group may act as a political interest group. METHODS: Residents of
      therapeutic facilities for mentally ill patients were questioned on their voting
      behaviour after the Federal Election to the Bundestag in 1994, 1998 and 2002.
      RESULTS: There was a stable preference for the parties from the "left wing", more
      than (2/3) of the study population voted for the Social Democrats or the Green
      party. It was important for 17.2 % of the clients that a party puts emphasis on
      the interests of the mentally ill. CONCLUSIONS: Chronic mentally ill patients
      show a different voting behaviour than the general population. Their voting
      decision is partially related to their specific interests, which could give them
      a lobby-like status. This should be taken into consideration in the future
      development and planning of mental health care systems.

PMID- 14658096
TI  - Corporate sponsorship and research: impact and outcome.

PMID- 14658095
TI  - Linkage at 12q24 with systemic lupus erythematosus (SLE) is established and
      confirmed in Hispanic and European American families.
AB  - Systemic lupus erythematosus (SLE) is a chronic, complex, and systemic human
      autoimmune disease, with both an environmental component and a heritable
      predisposition. Clinical studies, reinforced by epidemiology and genetics, show
      impressive variation in disease severity, expression, prevalence, and incidence
      by ethnicity and sex. To identify the novel SLE susceptibility loci, we performed
      a genomewide scan with 318 markers on 37 multiplex Hispanic families, using a
      nonparametric penetrance-independent affected-only allele-sharing method. Three
      chromosomal regions (12q24, 16p13, and 16q12-21) exceeded our predetermined
      threshold (Zlr>2.32; nominal P<.01) for further evaluation. Suspected linkages at
      12q24, 16p13, and 16q12-21 were tested in an independent data set consisting of
      92 European American (EA-1) and 55 African American (AA) families. The linkage at
      12q24 was replicated in EA-1 (Zlr=3.06; P=.001) but not in AA (Zlr=0.37; P=.35).
      Although neither the 16p13 nor the 16q12-21 was confirmed in EA-1 or AA, the
      suggestive linkage (Zlr=3.06; P=.001) at 16q12-21 is sufficient to confirm the
      significant linkage, reported elsewhere, at this location. The evidence for
      linkage at 12q24 in the 129 combined (Hispanic and EA-1) families exceeded the
      threshold for genomewide significance (Zlr=4.39; P=5.7x10-6; nonparametric
      LOD=4.19). Parametric linkage analyses suggested a low-penetrance, dominant model
      (LOD=3.72). To confirm the linkage effect at 12q24, we performed linkage analysis
      in another set of 82 independent European American families (EA-2). The evidence
      for linkage was confirmed (Zlr=2.11; P=.017). Therefore, our results have
      detected, established, and confirmed the existence of a novel SLE susceptibility
      locus at 12q24 (designated "SLEB4") that may cause lupus, especially in Hispanic
      and European American families.

PMID- 14658097
TI  - Long-term follow-up care recommendations after total hip and knee arthroplasty:
      results of the American Association of Hip and Knee Surgeons' member survey.
AB  - Long-term follow-up care is needed to evaluate and manage hip and knee
      arthroplasty outcomes, because impending failure may be asymptomatic. All active
      American Association of Hip and Knee Surgeons' members (N = 682) were surveyed
      for recommendations for follow-up care type and frequency, radiograph
      interpretation, and clinical indicators related to follow-up frequency intervals;
      and to describe reimbursement experiences and practice demographics. The response
      rate (65.5%, n = 447) established a 95% (+/-3%) confidence interval for the
      survey results. We found that 80% of respondents recommended annual or biennial
      orthopaedic clinical and radiographic examinations, with more frequent follow-up
      times for clinical or radiologic signs of failure, previous revision
      arthroplasty, previous joint sepsis, and subnormal periprosthetic bone quality.
      Further research is needed to correlate follow-up care type and frequency with
      outcomes, complications, and costs.

PMID- 14658098
TI  - Relationship between length of stay and dislocation rate after total hip
      arthroplasty.
AB  - The purpose of this study was to determine if decreased postoperative inpatient
      time (length of stay; LOS) after total hip arthroplasty (THA) was correlated with
      an increase in the dislocation rate after discharge. Reduced access to physical
      therapy, nursing reinforcement of dislocation precautions, and medical
      supervision could lead to a higher rate of adverse behaviors (such as
      inappropriate flexion and rotation) and accidents that might have otherwise been
      avoided in the initial 3 -months after surgery. We examined records from 850
      patients (2 surgeons) who underwent primary THA from 1993 to 1998. LOS had
      progressively decreased over the 4 years since implementation of a clinical
      pathway (CP) in late 1993. The average LOS in 1992 was 6.6 days and was lowest in
      1998 at 3.9 days. The dislocation rate before the CP was 0.5%. The dislocation
      rate increased significantly to 3.9% after implementation of the CP (P =.015).
      Use of the CP offers numerous advantages but is associated with a higher
      dislocation rate.

PMID- 14658099
TI  - Primary total knee arthroplasty for periarticular fractures.
AB  - We present a series of 6 patients with periarticular fractures of the knee that
      were treated by primary total joint arthroplasty. These fractures around in 6
      elderly women, three in the proximal tibia and three in the distal femoral. All
      the patients had osteoarthritis and osteopenia. In five patients, a hinged total
      knee arthroplasty was performed, and in one case an unconstrained prosthesis was
      performed. Cementing techniques were used in all. Postoperatively, immediate
      mobilization with full weight bearing was initiated. No radiographic or clinical
      evidence of loosening was seen, and the functional outcome was satisfying. The
      results suggest that another treatment option for intra-articular distal femoral
      or intra-articular proximal tibial fractures in elderly patients with severe
      osteopenia and osteoarthritis is primary total knee arthroplasty. Furthermore,
      this primary total knee arthroplasty may require some degree of constraint.

PMID- 14658101
TI  - Enhancing femoral cement fixation in total knee arthroplasty.
AB  - Several factors have been shown to be associated with early development of
      radiolucent lines at the bone-cement interface in total knee arthroplasty (TKA).
      The posterior condylar surfaces, in particular, seem subject to poor cement
      technique, which could lead to early loosening. This study compares two
      cementation techniques in TKA, with respect to depth of cement penetration and
      radiolucency in the posterior condyles. All penetration depths were greater in
      group I (injected) versus group II (noninjected). Sixty-seven percent of group I
      showed penetration depths >1.5 mm compared with 23% of group II. No specimen in
      group I had gaps in the cement mantle on visual inspection or radiolucency on
      radiographic evaluation. No statistical differences, however, could be
      demonstrated between the two groups.

PMID- 14658100
TI  - An evaluation of the safety and efficacy of simultaneous bilateral total knee
      arthroplasty.
AB  - This study directly compared the clinical and radiographic results and patient
      satisfaction of a group of simultaneous, bilateral total knee arthroplasties (92)
      with a year of surgery matched unilateral total knee arthroplasties (92). Death
      within 1 month of surgery occurred in 1 bilateral patient and no unilateral
      patients. Significant cardiorespiratory complications were recorded in 6
      bilateral patients and 2 unilateral patients. Patients with pre-existing
      cardiorespiratory conditions were particularly at risk. Analysis revealed a 98% 7
      year survivorship for unilateral procedures and 97% for bilateral. In this study,
      95% of bilateral patients stated they would choose the same option again.

PMID- 14658102
TI  - 15-year follow-up study of total knee arthroplasty in patients with rheumatoid
      arthritis.
AB  - In 25 patients with rheumatoid arthritis, 36 cases of cemented Kinematic total
      knee arthroplasty were reviewed clinically and radiographically at 13 to 19 years
      after surgery. The mean age at the time of surgery was 51.6 +/- 8.9 years.
      According to the follow-up results evaluated with the Hospital for Special
      Surgery knee scoring system, 28 knees (77.7%) were classified as good or
      excellent. The mean flexion angle at follow-up evaluation was 99 degrees +/- 24
      degrees (10 degrees -140 degrees ). At the tibial or femoral bone-cement
      interfaces, a radiolucent line was seen in 10 of 36 knees (27.8%) at follow-up
      evaluation. The survival rate of prostheses with revision as the endpoint was
      estimated to be 93.7% at 15 years. Kinematic total knee arthroplasty in
      rheumatoid arthritis patients provided a good long-term outcome.

PMID- 14658103
TI  - Secondary patellar resurfacing in total knee arthroplasty: results of
      multivariate analysis in two case-matched groups.
AB  - Although patellofemoral symptoms after patellar-retaining knee arthroplasty are
      common, no evidence has been published in the literature on the potential benefit
      from patellar resurfacing at a later stage. This study evaluates the effect of
      secondary (delayed) patellar resurfacing using comparisons between 2 case-matched
      groups of patients with primary and secondary patellar resurfacing. Furthermore,
      multivariate statistical methods were applied to study factors that may influence
      the final outcome. Our results suggest that although significant clinical
      improvement was seen after delayed patella resurfacing, the outcome of secondary
      patellar resurfacing is inferior to that expected for a similar group of patients
      with primary resurfacing. Furthermore, the timing (delay period) of the secondary
      resurfacing procedure appears to negatively affect the final outcome. This
      suggests that secondary patellar resurfacing, when indicated, should be
      considered at an early stage.

PMID- 14658104
TI  - Cemented first-time revision using Charnley cups: clinical outcome after 7 to 15
      years follow-up.
AB  - Forty-six consecutive polyethylene cups used in cemented first-time revision of
      the acetabulum were evaluated at repeated occasions up to mean 10.7 years (range,
      0.5-16.3 years). At the last follow-up, 3 cups had been revised (6.5%), 2 because
      of loosening and 1 because of fracture of the acetabulum. Furthermore, 4 were
      radiographically loose, corresponding to a radiographic loosening rate of 13% and
      a mechanical failure rate (revision or radiographic loosening) of 15.2%. Presence
      of rheumatoid arthritis was the only predictor of mechanical failure (relative
      risk [RR] = 7.7, 95% confidence limits, 1.7-36.2; P =.002). In patients without
      rheumtoid arthritis, there was only 1 (2.6%) revision and 3 of 39 cases (7.7%)
      with mechanical failure. Recementation of a Charnley cup in first-time revisions
      results in a low failure rate in an elderly, nonrheumatoid arthritis population
      with small or moderate bone deficiencies.

PMID- 14658105
TI  - Radiographic evaluation of Charnley cups used in first-time revision: repeated
      observations for 7-15 years.
AB  - The radiographs of 46 consecutive polyethylene cups used in cemented first-time
      revision of the acetabulum were studied up to a mean of 10.7 years (range, 0.5
      16.3 years). Six cups developed loosening, of which 2 were revised. New
      radiolucent lines appeared mainly up to the 3 years follow-up. Progression of
      radiolucencies to new regions was noted in 28 (61%) cups. This progression
      occurred as an increase in extension from the periphery to the central region of
      the interface, whereas the width only showed minor changes. Our findings indicate
      that even radiolucent lines with a width <1.0 mm should be given attention
      because these lines can surround the cup before significant migration (>5 mm) is
      established. True lateral radiographs exposed to visualize the interface add
      information concerning presence of loosening. According to our opinion, complete
      radiolucent lines on either the anterior-posterior or lateral view, with a width
      of 0.3 to 0.5 mm or more, should be regarded as radiographic failure.

PMID- 14658106
TI  - Results of rotating-platform, low-contact-stress knee prosthesis.
AB  - Low-contact-stress (LCS) rotating-platform knee arthroplasties in 31 consecutive
      patients with 50 deformed knees were evaluated at a mean follow-up of 4.5 years
      (range, 4-6 years). Overall results were good in 72% of 22 osteoarthritic knees
      and 71.4% of 28 rheumatoid knees. None of the knees showed any change in
      component position and alignment, osteolysis, or cement-bone radiolucency during
      follow-up. LCS prosthesis takes care of some rotational component mismatch.
      Complications included 2% dislocation, 4% anteroposterior instability, and 10%
      subluxation of the rotating platform. The overall reoperation rate of 10% was
      significantly higher than reported for the fixed bearing series, and we feel that
      LCS prosthesis is unsuitable for severely deformed knees.

PMID- 14658107
TI  - Patellar clunk syndrome after posterior stabilized total knee arthroplasty.
AB  - Two hundred thirty-six posterior stabilized total knee arthroplasties (TKAs) were
      performed consecutively. Twenty-seven patellar clunk syndromes were identified in
      25 patients. Insall-Salvati ratio, position of joint line, postoperative patellar
      height, and anterior-posterior position of tibial tray were measured. It was
      found that postoperative low-lying patella (P<.001) and anterior placement of
      tibial tray (P=.011) was associated with patellar clunk syndrome. Thirteen
      patients had bilateral TKAs of the same prosthesis (5 bilateral AMK knees and 8
      bilateral Insall Burstein knees) but unilateral patellar clunk syndrome. The
      nonclunk sides were used as control for comparison with the clunk sides. The
      congruency and tilting of the patellar button in the skyline view were
      documented. It was observed that the congruency of the patellar button was less
      satisfactory in the clunk side (P=.019).

PMID- 14658108
TI  - Kinematic analysis of a posterior cruciate retaining mobile-bearing total knee
      arthroplasty.
AB  - Using video fluoroscopy, 10 subjects having a mobile-bearing posterior cruciate
      retaining total knee arthroplasty were analyzed to determine their in vivo
      kinematic patterns. Under weight-bearing conditions, while in extension, the
      average contact position was posterior to the mid-tibia sagittal plane with
      posterior translation of both condyles to 60 degrees of flexion, followed by
      anterior translation to 120 degrees of flexion. Under non-weight-bearing
      conditions, the average condylar contact positions were significantly more
      anterior from full extension to 90 degrees of knee flexion (P=.01). The average
      range of motion was 129 degrees under non-weight-bearing conditions and 119
      degrees during weight-bearing. Although subjects in this study exhibited variable
      motion patterns, they are accommodated by the unconstrained optimized
      articulation of this highly conforming mobile-bearing implant.

PMID- 14658109
TI  - The value of white blood cell counts before revision total knee arthroplasty.
AB  - A white blood cell count (WBC) of >50000 cell/mm(3) from a knee aspirate with
      >or=80% polymorphonuclear cells (PMNCs) is suggestive of infection. This study
      sought to determine if these same criteria were applicable when interpreting
      aspirates from a total knee. Of 440 revision total knee arthroplasties, 86
      patients had preoperative aspirations of the knee before revision. Fifty-five
      aspirates were from aseptic failures; 31 aspirates were from patients determined
      to have septic failure. The mean white blood cell (WBC) count in aspirates from
      the aseptic group was 645 cells/mm(3) (SD = 878). The mean WBC count in the
      septic group was 25951 cells/mm(3) (SD = 34994; P=<.001). The mean percentage of
      PMNCs was statistically higher in the septic group compared with the aseptic
      group (72.8% vs 27.3%; P=<.001). The synovial fluid WBC count differential
      analysis is a statistically relevant indicator of the presence or absence of
      infection in revision knee arthroplasty. Aspirates with a WBC count of 2500 per
      milliliter and 60% PMNCs are highly suggestive of infection.

PMID- 14658110
TI  - Incidence of undiagnosed sleep apnea in patients scheduled for elective total
      joint arthroplasty.
AB  - We investigated the frequency of undiagnosed sleep apnea in patients scheduled
      for elective total joint arthroplasty. Two hundred fifty-four patients were
      assessed between September 1999 and May 2001. At intake, patients were given a
      standard systems review with the addition of targeted questions about sleep
      apnea. Ten patients reported symptoms consistent with undiagnosed obstructive
      sleep apnea (OSA). The identification of undiagnosed OSA is an issue for
      orthopedic practice because many patients referred to an arthroplasty service for
      hip and/or knee surgeries are obese. A few screening questions, readily
      incorporated into the preoperative assessment, may prevent perioperative
      complications such as postextubation airway obstruction, negative pressure
      pulmonary edema, or opioid-induced airway obstruction.

PMID- 14658111
TI  - Tibial axis and patellar position relative to the femoral epicondylar axis during
      squatting.
AB  - A laboratory-based study was performed to describe the tibial axis and patellar
      position relative to the femoral epicondylar (FE) axis during squatting. During
      the squat, the angle between the tibial and FE axes averaged 90.5 degrees, and
      66% of internal rotation of the tibia occurred before 15 degrees flexion. In the
      mid-sagittal plane of the femur, the patella followed a circular arc, and
      mediolateral patellar shift averaged 4.3 mm. These findings can be used as the
      basis for development of new total knee arthroplasty components that recreate
      normal patellofemoral kinematics, and may provide important guidelines for
      alignment of the tibial and femoral components. The perpendicular relationship
      between the tibial and the FE axes may be useful in locating the FE axis
      intraoperatively. The reduced mediolateral shift of the patella suggests that
      alignment of the femoral component with the FE axis will aid patellar tracking
      about a circular arc with small deviations in the medial-lateral direction.

PMID- 14658112
TI  - The initial stability of cemented acetabular cups can be augmented by mixing
      morsellized bone grafts with tricalciumphosphate/hydroxyapatite particles in bone
      impaction grafting.
AB  - Tricalciumphosphate (TCP) and hydroxyapatite (HA) have been suggested as bone
      graft substitutes in a wide range of applications. In this study, the initial
      stability of cemented acetabular cups was determined after reconstructing a
      combined cavitary and segmental defect in a realistic acetabular revision surgery
      model. The defects were reconstructed with mixes of TCP/HA particles and human
      bone grafts using the bone impaction grafting technique. In comparison with
      defect reconstruction with human bone grafts only, cup translation and tilt
      decreased by 27% when mixes of bone grafts and porous TCP/HA particles were used
      and by 55% when mixing the bone grafts with solid TCP/HA particles. Increasing
      the TCP/HA ratio within the mix significantly decreased cup translation. From a
      biomechanical perspective, mixes of TCP/HA particles and bone grafts are an
      attractive alternative for morsellized bone grafts when using the bone impaction
      grafting technique in the reconstruction of large defects of the acetabulum.

PMID- 14658113
TI  - A stem-allograft composite for femoral revision in total hip arthroplasty.
AB  - Femoral revision is difficult when the femoral canal exceeds 20 mm in diameter.
      For this subset of patients, we used a technique of cementing cortical allograft
      sleeves to a proximal ingrowth stem. The diameter of the allograft sleeves are
      matched to the diameter of the host femur. The stem-allograft construct provides
      initial stability with the opportunity for proximal bone ingrowth.

PMID- 14658114
TI  - Recurrent dislocation of total knee arthroplasty: an unusual cause.
AB  - We report an unusual case of recurrent dislocation of posterior stabilized total
      knee arthroplasty (TKA) secondary to fracture of the polyethylene insert.
      Recurrent dislocation occurred 21 months after primary TKA. Fractured
      polyethylene insert was noted as an abnormal radiolucent shadow on postoperative
      radiographs and was confirmed by an arthrogram. At revision surgery,
      disintegration of the insert, including the tibial post, was found. We recommend
      careful scrutiny of the integrity of the polyethylene insert at the time of
      follow-up evaluation in cases of TKA dislocation.

PMID- 14658115
TI  - Gigantic popliteal synovial cyst caused by wear particles after total knee
      arthroplasty.
AB  - We present a case exhibiting persistent joint effusion and formation of a
      gigantic popliteal synovial cyst 8 years after total knee joint arthroplasty.
      Assessment using flow cytometry revealed that both joint and cyst fluid contained
      abundant macrophage-phagocytosing wear particles. This finding indicates that
      wear particles participated in formation of the cyst through the communication
      between the joint cavity and cyst. Intraoperatively, prominent villous synovial
      proliferation was observed in both the joint and cyst, and delamination failure
      of the polyethylene insert was identified. Because no evidence of prosthetic
      loosening was found, only polyethylene insert revision and synovectomy were
      undertaken, resulting in a successful outcome. This case suggests that synovial
      cyst formation in popliteal lesions might represent a sign of wear-particle
      generation after total knee joint arthroplasty.

PMID- 14658123
TI  - [How can malabsorption syndrome be treated?].

PMID- 14658124
TI  - Low-intensity versus conventional-intensity warfarin for prevention of recurrent
      venous thromboembolism.

PMID- 14658125
TI  - Low-intensity versus conventional-intensity warfarin for prevention of recurrent
      venous thromboembolism.

PMID- 14658126
TI  - Low-intensity versus conventional-intensity warfarin for prevention of recurrent
      venous thromboembolism.

PMID- 14658127
TI  - Low-intensity versus conventional-intensity warfarin for prevention of recurrent
      venous thromboembolism.

PMID- 14658128
TI  - Coronary angioplasty versus fibrinolytic therapy in acute myocardial infarction.

PMID- 14658129
TI  - Coronary angioplasty versus fibrinolytic therapy in acute myocardial infarction.

PMID- 14658130
TI  - Case 27-2003: a 36-year-old man with recurrent epigastric pain and elevated
      amylase levels.

PMID- 14658131
TI  - Special issue dedicated to Professor Kazuhiro Imai on the occasion of his
      retirement from Tokyo University.

PMID- 14658132
TI  - Effect of a Fast-skin 'body' suit on drag during front crawl swimming.
AB  - The effect on drag of a Speedo Fast-skin suit compared to a conventional suit was
      studied in 13 subjects (6 males, 7 females) swimming at different velocities
      between 1.0 and 2.0 m.s-1. The active drag force was directly measured during
      front crawl swimming using a system of underwater push-off pads instrumented with
      a force transducer (MAD system). For a range of swimming speeds (1.1, 1.3, 1.5
      and 1.7 m.s-1), drag values were estimated. On a group level, a statistically non
      significant drag reduction effect of 2% was observed for the Fast-skin suit (p =
      0.31). Therefore, the 7.5% reduction in drag claimed by the swimwear manufacturer
      was not corroborated.

PMID- 14658133
TI  - Biomechanical analysis of the grab, track and handle swimming starts: an
      intervention study.
AB  - This study examined the grab, track and handle swimming racing starts by
      elitelevel swimmers. Videography was used to analyse these starts before and
      after a period of dive start practice. Participants underwent 2-4 sessions weekly
      until 14 +/- 2 practice sessions were completed. Practice sessions comprised 5
      grab starts (preferred technique) and 10 handle starts; or 5 grab starts and 10
      track starts. The performance criterion measure was time to 10 m. Reaction,
      movement, block and flight times, flight distance, and the centre of mass at the
      set position were measured. No significant differences between dive groups in
      time to 10 m were revealed pre- or post-training. The training period further
      exaggerated the differences in centre of mass positions in the set position
      between the three techniques. The handle start revealed a significant change
      forward in the centre of mass that allowed for decreased movement and block
      times. The training period improved 10 m, reaction, movement, block and flight
      times irrespective of the technique used. Hence, regular dive start practice
      significantly improved the start performances of elite swimmers. Coaches should
      consider including regular dive practice sessions of approximately 15 minutes to
      improve dive start performances.

PMID- 14658134
TI  - A kinetic analysis of discus-throwing techniques.
AB  - The purposes of this study were to investigate (1) the relationships between
      official distance and selected ground reaction measures during discus throwing;
      and (2) the relationships between selected ground reactions and selected lower
      extremity joint kinetics. Three high-speed video cameras and three force plates
      were used to collect three-dimensional videographic and force plate data in this
      study. An inverse dynamic model was used to determine the lower extremity
      kinetics. Multiple regression analyses were conducted to determine relationships
      of the selected kinematic and kinetic measures with the official distance.
      Official distance was significantly correlated with ground reaction forces on the
      left foot during the first single-support phase, on the right foot during the
      second single-support phase and delivery phase, and on the left foot during the
      delivery phase. Also, the right-hip extension and internal rotation moments and
      left-knee extension moment during the delivery phase were significantly
      correlated with official distance. These results suggest that discus throwers
      should drive vigorously forward during the first single-support phase and
      increase the landing impact force on the right foot after flight. Also they
      should increase forward and rightward ground reaction force on the right foot and
      backward and vertical force on the left foot by powerful right-hip extension and
      internal rotation and left-knee extension during the delivery phase. These
      results provide critical information regarding the training of discus-throwing
      techniques, and the direction of future biomechanical studies on this event.

PMID- 14658135
TI  - The one- and two-handed backhands in tennis.
AB  - The study investigated differences in the one- (SH) and two-handed (DH) backhands
      when hit flat, across-court (AC) and down-the-line (DL), and with heavy topspin
      DL (TDL). The ability to disguise each of these backhands when hitting the above
      strokes was also assessed. Eighteen college-level male tennis players, identified
      as having a high performance topspin SH (n = 6) or DH (n = 12) backhand drive,
      participated in the study. Players were required to hit three AC, DL and TDL
      backhands from the baseline with their preferred technique, while being filmed
      with two high-speed video cameras operating at 200 Hz. The highest horizontal
      velocity backhand for each stroke was analysed. Results indicated that the
      sequential coordination of five body segments (hips, shoulder, upper arm,
      forearm, and hand/racquet rotations) was required for the execution of the SH
      stroke. The same number of segments were generally coordinated in the DH stroke
      (hips, shoulders, and varying degrees of upper arm and forearm rotations followed
      by hand/racquet movement). Mature players produced comparable racquet horizontal
      velocities 0.005 s prior to impact using either the SH or DH backhand technique.
      The SH backhand was characterised by a more rotated shoulder alignment than the
      DH stroke (SH: 119.1 degrees; DH: 83.4 degrees) at the completion of the
      backswing. At impact the ball was impacted further in front (SH: 0.59 m: DH: 0.40
      m) and a similar distance to the side of the body (SH: 0.75 m: DH: 0.70 m).
      Players using the DH backhand technique delayed the horizontal acceleration of
      the racquet towards the ball (SH: 0.13 s: DH: 0.08 s prior to impact) and thus
      were capable of displaying a similar hitting motion closer to impact than players
      with a SH technique.

PMID- 14658136
TI  - Comparative analysis of selected biomechanic characteristics between a support
      backward swing and support swing for the 1 1/4 straddle-piked forward salto on
      the parallel bars.
AB  - The aim of our research was to study the relationships between performance
      variables in a support backward swing (SBS), which was used as a progressive step
      in the learning procedure for a 1 1/4 straddle-piked front somersault and the
      swing prior to a 1 1/4 straddle-piked front somersault from support to bent arm
      support on the parallel bars (5/4S). Mitja Petkovsek, parallel bars gold
      medallist at the 2000 EC in Bremen, performed these elements. Kinematic analysis
      involved CMAS software (Praha, 1993), and the Suskana body segment model that has
      17 points and 15 segments. Kinetic variables were estimated using 2D IMGIM
      software, which has 8 points and 6 segments (Colja and Cuk, 1994). The results
      indicated that some kinematic aspects of the two types of swings were similar but
      there were important differences in kinetic aspects of the motion. During the
      swing for the 5/4S, force and torque were higher than in the SBS.

PMID- 14658137
TI  - Training principles: evaluation of modes and methods of resistance training--a
      coaching perspective.
AB  - Current information and evidence indicate that for most activities free weight
      training can produce superior results compared to training with machines,
      particularly when the free weight training involves complex, multi-joint
      exercises. A number of reasons can account for the superiority of free weights;
      the major factor deals with mechanical specificity. Mechanical specificity is
      concerned with appropriate movement patterns, force application and velocity of
      movement. Considering the available evidence that adherence to the concept of
      specificity of exercise and training can result in a greater transfer of training
      effect then free weights should produce a more effective training transfer.
      Therefore, the majority of resistance exercises making up a training programme
      should include of free weight exercises with emphasis on mechanical specificity
      (i.e. large muscle mass exercises, appropriate velocity, contraction type etc.).
      Generally, machines should be used as an adjunct to free weight training and,
      depending upon the sport, can be used to a greater or lesser extent during
      various phases of the training period (preparation, pre-competition,
      competition).

PMID- 14658138
TI  - A computer-graphics model of muscle activation and contraction dynamics.
AB  - An interactive computer-graphics model of the mechanical interaction between the
      structural components of a Hill-type muscle model is presented. The model allows
      the length, velocity, and force in the contractile component, parallel elastic
      component, and series elastic of a generic (normalised) muscle-tendon complex to
      be computed from input defining instantaneous muscle stimulation and muscle
      tendon length. By altering model inputs and model parameter values the user can
      observe corresponding model behaviour in schematic and graphical form. In this
      paper a general description of the model is provided together with examples of
      how the model can be used to simulate different contractile conditions. It is
      intended that the model will serve as a useful tool for demonstrating the
      behaviour of Hill-type muscle models.

PMID- 14658140
TI  - Hazard report. Specialty tables require special attention.

PMID- 14658139
TI  - Needlestick-prevention devices. Disposable syringes and injection needles.
AB  - Needlestick-prevention devices (NPDs) are an essential tool for protecting
      healthcare workers from injuries that could result in exposure to bloodborne
      pathogens. More than a dozen NPD varieties are available. They generally take the
      same form as conventional (nonsafety) sharps but incorporate some type of safety
      design--for example, a shield or a needle-retracting mechanism. In this
      Evaluation, we focus on protective devices that are used in place of conventional
      syringes and injection needles--namely, disposable protective syringes and needle
      guards. We tested 14 products from 8 suppliers. We give Preferred ratings to
      three products, all of which are needle-retracting syringes. When used correctly,
      these devices provide the best protection available. However, their primary
      safety advantage--preremoval activation--can be negated if the user chooses to
      activate the safety mechanism after removing the needle from the patient. For
      many facilities, one of the seven models we rate Acceptable might be a better
      choice. We caution that our ratings should not be the sole basis of a purchase
      decision. Staff members need to conduct a hands-on assessment of the available
      products to identify those that best meet their needs. We also stress that any
      NPD--even one we rate Not Recommended--is preferable to using no protective
      device at all.

PMID- 14658141
TI  - User Experience Network. Leaving leg plates down when lowering surgical tables
      may crack table base.

PMID- 14658142
TI  - Surface plasmon resonance imaging as a tool to monitor biomolecular interactions
      in an array based format.

PMID- 14658143
TI  - Femtosecond broadband stimulated Raman: a new approach for high-performance
      vibrational spectroscopy.
AB  - Femtosecond stimulated Raman spectroscopy (FSRS) is a new technique that produces
      high-quality vibrational spectra free from background fluorescence. FSRS combines
      a narrow-bandwidth picosecond Raman pump pulse with an approximately 80 fs
      continuum probe pulse to produce stimulated Raman spectra from the pump-induced
      gain in the probe spectrum. The high intensity of the Raman pump combined with
      the broad bandwidth of the probe produces high signal-to-noise vibrational
      spectra with very short data acquisition times. FSRS spectra of standard
      solutions and solvents such as aqueous Na2SO4, aqueous KNO3, methanol,
      isopropanol, and cyclohexane are collected in seconds. Furthermore, stimulated
      Raman spectra can be obtained using just a single pump-probe pulse pair that
      illuminates the sample for only approximately 1 ps. Fluorescence rejection is
      demonstrated by collecting FSRS spectra of dyes (rhodamine 6G, chlorophyll a, and
      DTTCI) with varying degrees of fluorescence background and resonance enhancement.
      The high signal-to-noise, short data acquisition time, fluorescence rejection,
      and high spectral and temporal resolution of femtosecond stimulated Raman
      spectroscopy make it a valuable new vibrational spectroscopic technique.

PMID- 14658144
TI  - Confocal Raman microspectrometry: a vectorial electromagnetic treatment of the
      light focused and collected through a planar interface and its application to the
      study of a thin coating.
AB  - In-depth confocal Raman microspectrometry (CRM) studies through a planar
      interface between materials of mismatched refraction indices are known to be
      affected by a decrease of both the collected Raman intensity and the axial
      resolution as a function of the penetration depth. Following a previous model,
      which takes the refraction, diffraction, and spherical aberration effects into
      account when focusing a Gaussian incident laser beam with a high numerical
      aperture objective lens, a complete vectorial treatment of these phenomena is
      considered. It is demonstrated that off-axis refraction effects cannot be
      neglected and that the dimension of the confocal pinhole aperture plays a crucial
      role on the effective focal plane position and on the collection efficiency. We
      thus propose a more rigorous and complete approach to the problem, and we find a
      very good agreement between experimental and theoretical Raman intensity
      variations for a thick polyethylene sample as a function of the penetration
      depth. As compared with calculations where only refraction was considered, we
      confirm that the lengthening of the focus even for a large penetration depth is
      significantly reduced upon diffraction effects. As an illustrative example, the
      theoretical Raman responses for a thin coating of approximately 20 microns on a
      polymer substrate were investigated and compared to experimental results already
      published. Even though the interfacial region is spread over approximately 5-6
      microns when using a 100x objective and a confocal pinhole of 200 microns
      diameter, it is definitively concluded that the apparent axial resolution is not
      drastically deteriorated with increasing depth and that the coating thickness may
      be directly estimated with a precision of approximately 1.0 micron (5%).

PMID- 14658145
TI  - Micro-Raman densimeter for CO2 inclusions in mantle-derived minerals.
AB  - We investigated the applicability of Raman microprobe spectroscopy for
      determining the density of CO2 in fluid inclusions in minerals of mantle-derived
      xenolith samples. A separation (delta) between two Raman bands of CO2 due to
      Fermi resonance can be a reliable densimeter for CO2 fluid. The relationship
      between the density of CO2 (g/cm3) and delta (cm-1) can be expressed as: d = 
      0.03238697 delta 3 + 10.08428 delta 2 - 1046.189 delta + 36163.67. This equation
      was obtained from the Raman data on CO2 fluid with densities from 0.1 to 1.21
      g/cm3, including super critical fluids at 58-59 degrees C. The delta value was
      constant with increasing temperature from room temperature to 200 degrees C. This
      indicates that the Raman densimeter is not affected by a possible rise in
      temperature, an artifact induced by the high flux of the incident laser. The
      minimum size of measurable inclusions is 1 micron, and the precision in the
      determination of delta is 0.1 cm-1, corresponding to 0.02 g/cm3 for inclusions of
      1 micron in size. The precision can be better for larger inclusions. The micro
      Raman densimeter can determine the density of CO2 fluid inclusions over a wide
      range. In particular, densities of gas and mixtures of gas and liquid phases,
      which cannot be measured by microthermometry, can be determined.

PMID- 14658146
TI  - Near-infrared surface-enhanced-Raman-scattering-mediated detection of single
      optically trapped bacterial spores.
AB  - A novel methodology has been developed for the investigation of bacterial spores.
      Specifically, this method has been used to probe the spore coat composition of
      two different Bacillus stearothermophilus variants. This technique may be useful
      in many applications; most notably, development of novel detection schemes toward
      potentially harmful bacteria. This method would also be useful as an ancillary
      environmental monitoring system where sterility is of importance (i.e., food
      preparation areas as well as invasive and minimally invasive medical
      applications). This unique detection scheme is based on the near-infrared (NIR)
      surface-enhanced Raman scattering (SERS) from single, optically trapped,
      bacterial spores. The SERS spectra of bacterial spores in aqueous media have been
      measured using SERS substrates based on approximately 60-nm-diameter gold
      colloids bound to 3-aminopropyltriethoxysilane derivatized glass. The light from
      a 787-nm laser diode was used to trap and manipulate as well as simultaneously
      excite the SERS of an individual bacterial spore. The collected SERS spectra were
      examined for uniqueness and the applicability of this technique for the strain
      discrimination of Bacillus stearothermophilus spores. Comparison of normal Raman
      and SERS spectra reveals not only an enhancement of the normal Raman spectral
      features but also the appearance of spectral features absent in the normal Raman
      spectrum.

PMID- 14658147
TI  - Studies of the optical properties of metal-pliable polymer composite materials.
AB  - Polymer-nano-metallic-particle composites have demonstrated technological
      potential due to their unique optical and electrical properties. Herein, we
      report on composites prepared via physical vapor deposition of silver metal onto
      pliable poly(dimethylsiloxane) (PDMS) polymer. Rapid Ag diffusion and nano
      metallic-particle formation in a phase-separated surface layer of the PDMS
      creates unique sub-surface-based composites whose properties vary based on rate
      of deposition and average Ag thickness. Additionally, nanometallic-particle
      spacing can be altered with fair reproducibility and reversibility by physically
      manipulating the Ag-PDMS composite. The optical properties of the materials are
      studied by visible wavelength optical extinction spectrometry and surface
      enhanced Raman scattering (SERS), including studies performed during physical
      manipulation. Direct current (DC) conductivity measurements were made during Ag
      deposition to study percolation conditions for the materials. Depth-profiling was
      performed by X-ray photoelectron spectrometry. Sample Raman spectral data
      collected with the composite as a SERS substrate are included. A practical
      technological characteristic of these composite materials arises from their
      potential to be molded into functional devices.

PMID- 14658148
TI  - Band-target entropy minimization (BTEM) applied to hyperspectral Raman image
      data.
AB  - Band-target entropy minimization (BTEM) has been applied to extraction of
      component spectra from hyperspectral Raman images. In this method singular value
      decomposition is used to calculate the eigenvectors of the spectroscopic image
      data set. Bands in non-noise eigenvectors that would normally be used for
      recovery of spectra are examined for localized spectral features. For a targeted
      (identified) band, information entropy minimization or a closely related
      algorithm is used to recover the spectrum containing this feature from the non
      noise eigenvectors, plus the next 5-30 eigenvectors, in which noise predominates.
      Tests for which eigenvectors to include are described. The method is demonstrated
      on one synthesized Raman image data set and two bone tissue specimens. By
      inclusion of small amounts of signal that would be unused in other methods, BTEM
      enables the extraction of a larger number of component spectra than are otherwise
      obtainable. An improvement in signal/noise ratio of the recovered spectra is also
      obtained.

PMID- 14658149
TI  - Automated method for subtraction of fluorescence from biological Raman spectra.
AB  - One of the challenges of using Raman spectroscopy for biological applications is
      the inherent fluorescence generated by many biological molecules that underlies
      the measured spectra. This fluorescence can sometimes be several orders of
      magnitude more intense than the weak Raman scatter, and its presence must be
      minimized in order to resolve and analyze the Raman spectrum. Several techniques
      involving hardware and software have been devised for this purpose; these include
      the use of wavelength shifting, time gating, frequency-domain filtering, first-
      and second-order derivatives, and simple curve fitting of the broadband variation
      with a high-order polynomial. Of these, polynomial fitting has been found to be a
      simple but effective method. However, this technique typically requires user
      intervention and thus is time consuming and prone to variability. An automated
      method for fluorescence subtraction, based on a modification to least-squares
      polynomial curve fitting, is described. Results indicate that the presented
      automated method is proficient in fluorescence subtraction, repeatability, and in
      retention of Raman spectral lineshapes.

PMID- 14658150
TI  - Image curvature correction and cosmic removal for high-throughput dispersive
      Raman spectroscopy.
AB  - A key factor determining the sensitivity of a Raman spectrometer is the usable
      detection area, which is the product of the usable slit width and the height. For
      the majority of process Raman samples, the larger the sampling area is, the more
      the scattered Raman signal can be gathered. On a multi-channel-detector-based
      dispersive spectrometer, a given spectral resolution limits the slit width.
      Extending the slit height using a straight slit usually causes the image to be
      curved on the detector due to optical effects. If left untreated, the curved slit
      image will degrade the peak shape and spectral resolution; therefore, the slit
      height must also be kept small if this negative effect is to be avoided. The
      mechanism of the curvature formation was analyzed for an on-axis-lens-based
      spectrograph, and a correction technique was developed to generate a straight
      slit image on the charge-coupled device (CCD). This allowed a large portion of
      the CCD height to be used without degrading the spectral resolution. A large
      fiber bundle was usable instead of a single small core fiber, generating
      significant increase in collected signal strength in clear or translucent
      samples. The straight image also enabled a new cosmic spike removal method,
      wherein the CCD image was divided into multiple strips, and a comparison among
      them allowed the identification and removal of cosmic spikes in a single CCD
      integration. On the contrary, many existing cosmic removal methods rely on
      comparison of multiple sequentially acquired spectra, potentially introducing
      artifacts, particularly when the spectral features are changing.

PMID- 14658151
TI  - Application of two-dimensional correlation spectroscopy to chemometrics: self
      modeling curve resolution analysis of spectral data sets.
AB  - This paper demonstrates the use of two-dimensional (2D) correlation spectroscopy
      in conjunction with alternating least squares (ALS) based self-modeling curve
      resolution (SMCR) analysis of spectral data sets. This iterative regression
      technique utilizes the non-negativity constraints for spectral intensity and
      concentration. ALS-based SMCR analysis assisted with 2D correlation was applied
      to Fourier transform infrared (FT-IR) spectra of a polystyrene/methyl ethyl
      ketone/deuterated toluene (PS/MEK/d-toluene) solution mixture during the solvent
      evaporation process to obtain the pure component spectra and then the time
      dependent concentration profiles of these three components during the evaporation
      process. We focus the use of asynchronous 2D correlation peaks for the
      identification of pure variables needed for the initial estimates of the ALS
      process. Choosing the most distinct bands via the positions of asynchronous 2D
      peaks is a viable starting point for ALS iteration. Once the pure variables are
      selected, ALS regression can be used to obtain the concentration profiles and
      pure component spectra. The obtained pure component spectra of MEK, d-toluene,
      and PS matched well with known spectra. The concentration profiles for components
      looked reasonable.

PMID- 14658152
TI  - Two-dimensional fluorescence correlation spectroscopy: resolution of fluorescence
      of tryptophan residues in horse heart myoglobin.
AB  - Generalized two-dimensional (2D) fluorescence correlation spectroscopy has been
      used to resolve fluorescence of two tryptophan (Trp) residues in horse heart
      myoglobin. Fluorescence quenching is employed as a perturbation mode for causing
      intensity changes in the fluorescence (quenching perturbation). Two kinds of
      quenchers, iodide ion and acrylamide, are used for inducing fluorescence
      intensity change. This technique works because the Trp residue located at the 7th
      position (W7) is known to be easily accessible to the quencher, whereas that
      located at the 14th position (W14) is not. By this technique, the fluorescence
      spectra of the two Trp residues were clearly resolved. From asynchronous maps, it
      was also shown that the quenching of W7 fluorescence is brought about prior to
      the quenching of W14 fluorescence. This result is consistent with the structure
      of horse heart myoglobin that was proposed earlier. Furthermore, it was
      elucidated that the present 2D analysis is not interfered with by Raman bands of
      the solvents, which sometimes brings difficulty into conventional fluorescence
      analysis.

PMID- 14658153
TI  - Time-resolved luminescence imaging of hydrogen peroxide using sensor membranes in
      a microwell format.
AB  - We demonstrate an optical imaging scheme for hydrogen peroxide in a microwell
      based format using the europium(III) tetracycline complex as the fluorescent
      probe, which is incorporated into a polyacrylonitrile-co-polyacrylamide polymer
      matrix. The resulting sensor membranes are integrated into a 96-microwell plate.
      Hydrogen peroxide can be visualized by means of time-resolved luminescence
      lifetime imaging. The imaging system consists of a fast, gated charge-coupled
      device (CCD) camera and a pulsed array of 96 light emitting diodes (LEDs).
      Fluorescence lifetime images are acquired in different modes (rapid lifetime
      determination, RLD, and phase delay rationing, PDR) and compared with
      conventional intensity-based methods with respect to sensitivity and the dynamic
      range of the sensor. The lowest limits of detection can be achieved by the RLD
      method. The response time of the sensor is comparatively high, typically in the
      range of 10 to 20 minutes, but the response is reversible. The largest signal
      changes are observed at pH values between 6.5 and 7.5.

PMID- 14658154
TI  - Spectroscopic studies on the darkening of lead white.
AB  - Lead white is an historically important paint used by artists since antiquity.
      The darkening of lead white has been well documented in works of art such as
      paintings. In this paper, mid-infrared (MIR) and visible spectroscopy were used
      to examine spectral changes accompanying the darkening of lead white paint as a
      result of exposure to H2S(g). Laboratory-prepared paint and a commercial lead
      white paint were used to observe the darkening reaction over time. Structural
      changes to the pigment, 2PbCO3.Pb(OH)2, in lead white were readily detected using
      MIR by applying a thin film on a KBr pellet. Spectral changes at 3541 (O-H
      stretch), 1400 (C-O), and 680 cm-1 (C-O) were the most significant over time as
      the paint darkened. Visible spectra were also collected to provide a semi
      quantitative measure of color change with structural changes observed by MIR.
      Experiments in the visible region were also conducted to compare the spectral
      response as % reflected and % transmitted light as lead white darkened. The
      effect of different binding agents (egg tempera, linseed oil, water, and gum
      Arabic) on the rate of darkening of lead white was also examined. Other sulfur
      containing pigments such as orpiment and realgar were also tested for their
      ability to darken lead white. By applying paint as a thin film inside a sealed
      cuvette, darkening of lead white was observed in the visible spectra (800 nm)
      when either powdered orpiment or realgar was in placed in the cuvette for 24 h.

PMID- 14658155
TI  - Main inorganic component measurement of seawater using near-infrared
      spectroscopy.
AB  - The potential of near-infrared (NIR) spectroscopy to measure the main inorganic
      components of seawater as salt-manufacturing materials was investigated. A total
      of 72 seawater samples collected from six locations was used, and spectra (1100
      1800 nm) were acquired by a NIR spectrophotometer with a 1-mm path length.
      Principal component analysis (PCA), canonical correlation analysis (CCA), and
      partial least-squares (PLS) regression were performed based on the reference
      inorganic components. As a result, the principal component analysis and canonical
      correlation analysis showed that the near-infrared spectra could be related to
      the inorganic components of seawater. The partial least-squares regression
      analysis showed that the inorganic components (ion concentration of Cl, Na+, K+,
      SO4(2-), and Ca2+) could be predicted with good accuracy using NIR spectra and
      their second derivatives. For Cl ion and K+ ion concentrations, the accuracy was
      high.

PMID- 14658156
TI  - Stopped flow apparatus for time-resolved Fourier transform infrared difference
      spectroscopy of biological macromolecules in 1H2O.
AB  - Stopped flow spectroscopy is an established technique for acquiring kinetic data
      on dynamic processes in chemical and biochemical reactions, and Fourier transform
      infrared (FT-IR) techniques can provide particularly rich structural information
      on biological macromolecules. However, it is a considerable challenge to design
      an FT-IR stopped flow system with an optical path length low enough for work with
      aqueous (1H2O) solutions. The system presented here is designed for minimal
      sample volumes (approximately 5 microL) and allows simultaneous FT-IR rapid-scan
      and VIS measurements. The system employs a micro-structured diffusional mixer to
      achieve effective mixing on the millisecond time scale under moderate flow and
      pressure conditions, allowing measurements in a cell path length of less than 10
      microns. This makes it possible to record spectra in 1H2O solutions over a wide
      spectral range. The system layout is also designed for a combination of kinetic
      and static measurements, in particular to obtain detailed information on the
      faster spectral changes occurring during the system dead time. A detailed
      characterization of the FT-IR stopped flow system is presented, including a
      demonstration of the alkaline conformational transition of cytochrome c as an
      example.

PMID- 14658157
TI  - Infrared method for in situ studies of polymer/surfactant adsorption on silica
      powders from aqueous solution.
AB  - This article presents a general infrared spectroscopic method that enables the
      monitoring of the adsorption of surfactants and polyelectrolytes on high surface
      area silica particles from aqueous solution. The method is based on the use of a
      ZnSe internal reflection element (IRE) coated with a layer of titania particles.
      The titania surface is the converted to silica using atomic layer deposition with
      sequential addition of an amine catalyst, gaseous SiCl4, and water vapor. A
      minimum of three cycles is needed to produce a surface that mimics silica, as
      evidenced by the reaction of hexamethyldisilazane and zeta potential
      measurements. It is shown that the silicacoated titania particles on the ZnSe
      crystals are stable to flowing aqueous solutions below pH = 8 and can be used to
      study the dynamics of polymer/surfactant adsorption on silica.

PMID- 14658158
TI  - Determination of acid number and base number in lubricants by Fourier transform
      infrared spectroscopy.
AB  - This paper describes the development of practical Fourier transform infrared (FT
      IR) methods for the determination of acid number (AN) and base number (BN) in
      lubricants through the combined use of signal transduction via stoichiometric
      reactions and differential spectroscopy to circumvent matrix effects.
      Trifluoroacetic acid and potassium phthalimide were used as stoichiometric
      reactants to provide infrared (IR) signals proportional to the basic and acidic
      constituents present in oils. Samples were initially diluted with 1-propanol,
      then split, with one half treated with the stoichiometric reactant and the other
      half with a blank reagent, their spectra collected, and a differential spectrum
      obtained to ratio out the invariant spectral contributions from the sample.
      Quantitation for AN and BN was based on measurement of the peak height of the v(C
      = O) or v(COO) absorptions, respectively, of the products of the corresponding
      stoichiometric reactions, yielding a standard error of calibration of < 0.1 mg
      KOH/g oil. The AN/BN FT-IR methods were validated by the analysis of a wide range
      of new and used oils supplied by third parties, which had been analyzed by ASTM
      methods. Good correlations were obtained between the chemical and FT-IR methods,
      indicating that the measures are on the whole comparable. From a practical
      perspective, these new FT-IR methods have significant advantages over ASTM
      titrimetric methods in terms of environmental considerations, sample size, and
      speed of analysis, as well as the variety of oil types that can be handled. FT-IR
      analysis combining stoichiometric signal transduction with differential
      spectroscopy may be of wider utility as an alternative to titration in the
      determination of acid or basic constituents in complex nonaqueous systems.

PMID- 14658159
TI  - Remote detection of heated ethanol plumes by airborne passive Fourier transform
      infrared spectrometry.
AB  - Methodology is developed for the automated detection of heated plumes of ethanol
      vapor with airborne passive Fourier transform infrared spectrometry. Positioned
      in a fixed-wing aircraft in a downward-looking mode, the spectrometer is used to
      detect ground sources of ethanol vapor from an altitude of 2000-3000 ft.
      Challenges to the use of this approach for the routine detection of chemical
      plumes include (1) the presence of a constantly changing background radiance as
      the aircraft flies, (2) the cost and complexity of collecting the data needed to
      train the classification algorithms used in implementing the plume detection, and
      (3) the need for rapid interferogram scans to minimize the ground area viewed per
      scan. To address these challenges, this work couples a novel ground-based data
      collection and training protocol with the use of signal processing and pattern
      recognition methods based on short sections of the interferogram data collected
      by the spectrometer. In the data collection, heated plumes of ethanol vapor are
      released from a portable emission stack and viewed by the spectrometer from
      ground level against a synthetic background designed to simulate a terrestrial
      radiance source. Classifiers trained with these data are subsequently tested with
      airborne data collected over a period of 2.5 years. Two classifier architectures
      are compared in this work: support vector machines (SVM) and piecewise linear
      discriminant analysis (PLDA). When applied to the airborne test data, the SVM
      classifiers perform best, failing to detect ethanol in only 8% of the cases in
      which it is present. False detections occur at a rate of less than 0.5%. The
      classifier performs well in spite of differences between the backgrounds
      associated with the ground-based and airborne data collections and the
      instrumental drift arising from the long time span of the data collection.
      Further improvements in classification performance are judged to require
      increased sophistication in the ground-based data collection in order to provide
      a better match to the infrared backgrounds observed from the air.

PMID- 14658160
TI  - Measurement and modeling of ozone and nitrogen oxides produced by laser breakdown
      in oxygen-nitrogen atmospheres.
AB  - The production of ozone nad nitrogen oxides was studied during multiple laser
      breakdown in oxygen-nitrogen mixtures at atmospheric pressure. About 2000 laser
      shots at 10(10) W cm-2 were delivered into a sealed reaction chamber. The chamber
      with a long capillary was designed to measure absorption of O3, NO, and NO2 as a
      function of the number of laser shots. The light source for absorption
      measurements was the continuum radiation emitted by the plasma during the first
      0.2 microsecond of its evolution. A kinetic model was developed that encompassed
      the principal chemical reactions between the major atmospheric components and the
      products of laser breakdown. In the model, the laser plasma was treated as a
      source of nitric oxide and atomic oxygen, whose rates of production were
      calculated using measured absorption by NO, NO2, and O3. The calculated
      concentration profiles for NO, NO2, and O3 were in good agreement with measured
      profiles over a time scale of 0-200 s. The steady-state concentration of ozone
      was measured in a flow cell in air. For a single breakdown in air, the estimated
      steady-state yield of ozone was 2 x 10(12) molecules, which agreed with the model
      prediction. This study can be of importance for general understanding of laser
      plasma chemistry and for elucidating the nature of spectral interferences and
      matrix effects that may take place in applied spectrochemical analysis.

PMID- 14658161
TI  - Near-infrared spectroscopic comparison of antique and modern wood.

PMID- 14658162
TI  - [Silent murder kills at dawn].

PMID- 14658163
TI  - [Diabetic nephropathy. A matter of inflammation?].

PMID- 14658164
TI  - [Methodologic limitations in studies that try to compare different modalities of
      hemodialysis].

PMID- 14658165
TI  - [Statistic analysis of "de novo" cancer incidence in renal transplant patients: a
      new study methodology].

PMID- 14658166
TI  - [Renal donation and transplantation in Spain 2002].

PMID- 14658167
TI  - [Anti-glomerular basement membrane antibody mediated disease: revision of 32
      cases and follow-up at one year of the diagnosis].
AB  - Anti-basement membrane antibody mediated disease is an unfrequent entity but with
      a high mortality and morbidity. We present a revision of 32 patients diagnosed of
      anti-basement membrane antibody mediated disease between 1983 and 1997, and their
      evolution at one year of the diagnosis. The clinical pattern of presentation was
      as a Goodpasture's syndrome (glomerulonephritis and lung haemorrhage) in 15
      patients and glomerulonephritis without lung involvement in 17. We reviewed
      retrospectively the features at the clinical presentation, the different
      treatments, and the delay of the starting of it since the beginning of the
      symptoms, in order to evaluate a prognosis dats of the disease. After the
      retrospective study we deduce that anti-basement membrane antibody mediated
      disease has a high mortality although the different regimes of treatment applied
      (25%), and the need of renal replacement therapy at one year of diagnosis is also
      high (70.8%). The renal survival at one year of the diagnosis is low and the
      response to therapy depends on the serum creatinine value at the diagnosis. The
      contribution of immunocompetent leucocytes to renal hypercellularity suggests
      that both humoral and cell-mediated immunity play a role in this disease.

PMID- 14658168
TI  - [Metabolic syndrome in patients with essential hypertension].
AB  - We have studied 218 patients with Essential Hypertension. The aim of this study
      was to determine the prevalence of Metabolic Syndrome (MS) and Insulin resistance
      (IR) in hypertensive patients and to know the vascular risk associated with MS.
      Blood pressure (BP), body mass index (BMI), plasma insulin and serum lipids were
      measured. Plasma glucose was measured basal and after two hours of an oral load
      of 75 g. Vascular damage was evaluated by measurement of thickening of
      Intimal/Media complex (TI/MC) in carotid artery by ecco doppler ultrasonography
      and by the presence of microalbuminuria. IR was estimated by the calculation of
      the HOMA index of IR. A prevalence of MS of 62% was found and MS was
      statistically significant associated to vascular damage (p = 0.000). Fifty seven
      percent of the hypertensive patients who had MS had hypertrigliceridemia which
      was also related to vascular damage. The prevalence of microalbuminuria (MA) in
      this population of hypertensive patients was 28% and the presence of MA was
      significantly associated to (TI/MC) (p = 0000). The hypertensive patients who had
      vascular damage (a pathological value of TI/MC and or MA) were more frequently
      males with higher BP, higher BMI (30.45 +/- 4 vs 28.9 +/- 4.3 p = 0.014), more
      elevated plasma insulin levels (37.38 +/- 22 vs 24.86 +/- 12 p = 0.000) and
      higher triglyceride levels (2.33 +/- 1.29 vs 1.93 +/- 1.08 p = 0.019). IR was
      found in 75% of the patients. In a multivariate logistic analysis the independent
      variables that define vascular damage in hypertensive patients were: Age (p =
      0.05), male sex (p = 0.01), Systolic BP (p = 0.002) and IR (p = 0.001). In
      conclusion, MS is a frequent finding in hypertensive patients. The presence of MS
      of any of their components increase the vascular risk (TI/MC of carotid artery
      and microalbuminuria). IR is a common finding in these patients and appears to be
      one of the most important markers of vascular risk.

PMID- 14658169
TI  - [Experience with sevelamer in peritoneal dialysis].
AB  - BACKGROUND: Sevelamer is a non-absorbable phosphorus chelator that is not a
      source of aluminium, calcium or base. The clinical experience with sevelamer in
      peritoneal dialysis and in daily clinical practice is scarce. The aim of this
      study is to evaluate the results of therapy of hyperphosphoremia with sevelamer
      on serum phosphorus and phosphorus chelators requirements, in a peritoneal
      dialysis clinical practice. METHODS: Sevalamer 400 mg was prescribed to
      peritoneal dialysis patients with hyperphosphoremia who were treated with
      aluminium hydroxide or with calcium salts in the absence of hypocalcemia.
      Fourteen patients completed 12 months of therapy. RESULTS: The initial sevelamer
      dose was 2,280 +/- 760 mg/day, and was increased to 2,760 +/- 1,160 mg/day at 12
      months. At 12 months no patient was on aluminium salts and calcium salts had been
      significantly reduced. Phosphoremia (5.9 +/- 0.6 to 5.0 +/- 1.4 mg/dL, p =
      0.049), calcium-phosphorus product (59.8 +/- 5.8 to 48.6 +/- 12.5 mg2/dL2, p =
      0.01) and serum cholesterol (191 +/- 29 to 167 +/- 33 mg/dL, p = 0.02) decreased
      at 12 months. No significant changes were observed in serum triglycerides, total
      CO2 or PTH. Serum alkaline phosphatase increased at 6 months, but values returned
      to normal at 12 months. No changes were observed in serum gamma-glutamyl
      transpeptidase. Five patients were started on 1.25 (OH)2 vitamin D therapy.
      CONCLUSION: In peritoneal dialysis patients, sevelamer allows a satisfactory
      control of serum phosphorus levels and calcium-phosphorus product, while
      decreasing the amount of aluminium and calcium salts prescribed.

PMID- 14658170
TI  - [Results of the international hemodialysis study DOPPS in Spain and Europe].
AB  - The Dialysis Outcomes and Practice Pattern Study (DOPPS) is an international
      observational study of treatment conditions and medical outcomes in hemodialysis
      patients. Prospective sampling has yielded long-term observational data from
      randomly selected groups of patients receiving treatment at representative,
      randomly selected hemodialysis units in each country. The data shown were
      collected at 20 hemodialysis units/centers in Spain. The data pertaining to Spain
      -Sp--refers to 575 patients and their comparison with those of the Euro-DOPPS
      countries--Eu--(Germany, France, United Kingdom, Italy and Spain), which
      encompass 3,038 patients, represent the formal goal of this paper. Diabetes
      mellitus, at 21.5% in Eu and 21.7% in Sp, was the most common cause of renal
      insufficiency in dialysis and coronariopathy, as a concomitant disease, was
      present in 67.8% in Eu as opposed to 75.8% in Sp. Differences were observed in
      the incident of hypertension (73.4% in Eu vs 77.4% in Sp), hepatitis C (11.6% vs
      19.5%), depression (12.7 vs 16.2%) and left ventricular hypertrophy (54.9% vs
      62.3%). The patterns of vascular access were similar (79% vs 81% AV fistulas in
      Eu and Sp, and 10% synthetic grafts for both) and the mean applied dose of
      dialysis--Kt/V--smaller (1.19) in Sp than in Eu (1.24); likewise the duration of
      the dialysis (in minutes) was shorter (234 in Eu vs 217 in Sp) and the % of
      synthetic membranes used was smaller (60% in Eu vs 52% in Sp). There were no
      differences between the groups in the figures for urea, creatinine, albumin,
      nPCR, calcium, phosphate or PTH. There were also no differences in the mean
      values of Hb (10.7 for Eu vs 10.8 for Sp), given that the values of ferritin were
      noticeably lower in Sp (288 vs 355) and the dose of EPO/kg/week was higher to in
      Sp (115 vs 102); s.c. route was used in similar proportions (69% in Eu vs 67% in
      Sp). The level of medical care, understood as contact with the physician at all
      or almost all treatments, was noticeably better in Sp (90%) that in Eu (66%),
      whereas the number of patients per hour of specialized personnel and % of
      specialized staff, were smaller. Mortality (death/100 patients-years) was one
      point lower in Sp than in Eu (15.4 vs 16.3). These data suggest that an increment
      in dialysis time and in the percentage of synthetic membranes used, as well as in
      the supply of intravenous iron, would be justified.

PMID- 14658171
TI  - [Ionic dialysance to control the dose of dialysis. One year experience].
AB  - The Diascan equipment (Hospal) measures ionic dialysane which it derives the K
      and the Kt. If we divide the Kt obtained with Diascan between the Kt/V obtained
      by a simplified formula, it result a value of V for every patient. Entering this
      V in the Diascan software we can obtain a Kt/V (Diascan Kt/V), similar in theory
      to the simplified Kt/V. In the year 2002 we have controlled the delivered
      dialysis in our unit with the Diascan Kt/V. The aim of the present study was to
      study the agreement between de Diascan Kt/V and the Lowrie Kt/V. During the year
      2002, 63 patients have been dialyzed in monitors with Diascan equipment. We
      calculated the V of each patient by dividing the Kt Diascan between the Lowrie
      Kt/V in the same dialysis session. The mea of the two consecutive measurements
      was considered the V value. Throughout the year 2002, 7 agreement studies were
      realized. The inter-method variability was assessed by the relative difference
      (absolute difference Diascan Kt/V-Lowrie Kt/V, divided by the average of both
      tests). A good agreement was considered when the relative difference was equal or
      lower than 10%. In the 7 agreement studies realized, the mean of the relative
      difference oscilled between 5.2 and 6.6%, and the percentage of patients with a
      relative difference equal or lower than 10% oscilled between 83 and 91%. During a
      month, the Diascan Kt/V was controlled in all dialysis sessions in 41 patients
      (554 sessions in total). Failure in the lecture of Kt/V Diascan was observed in
      41 sessions (7%). A Diascan Kt/V greater than 1 (the minimum delivered dialysis
      considered in our unit) was obtained in 93% of the valid sessions. 38 of 41
      patients had a mean monthly Diascan Kt/V greater than 1. The coefficient of
      variability of any patient oscilled between 2.1 and 12.4% (mean 5.1%). Diascan
      Kt/V is good procedure for the monitoring the delivered dialysis without blood
      sampling or any additional costs.

PMID- 14658172
TI  - [Cytomegalovirus nephrotic syndrome].
AB  - The case of a 5 months old infant with a nephrotic syndrome after neonatal
      cytomegalovirus infection is reported. Genomic amplification nested-PCR for CMV
      was positive in renal biopsy. Treatment with gancyclovir was effective to
      maintain nephrotic syndrome remission. We stresses the importance to discharge an
      infections cause of the nephrotic syndrome of newborns and infants due to the
      possibility on curative treatment.

PMID- 14658173
TI  - [Polycystic liver disease without autosomal dominant polycystic kidney disease].
AB  - Polycystic liver disease is characterized by the presence of multiple bile duct
      derived epithelial cysts scattered in the liver parenchyma. The natural history
      and clinical manifestations of polycystic liver disease are based on the disease
      as it manifests in patients with autosomal dominant polycystic kidney disease
      (ADPKD). The occurrence of polycystic liver disease independently from polycystic
      kidney disease has been known for a long time. More recently, a gene for
      autosomal dominant polycystic liver disease has been identified on chromosome 19p
      13.2-13.1. Isolated polycystic liver disease is underdiagnosed and genetically
      distinct from polycystic liver disease associated with ADPKD but with similar
      pathogenesis and clinical manifestations. We report here two men with polycystic
      liver disease no associated with ADPKD. Ultrasound and computed tomography
      imaging were effective in documenting the underlying lesions non-invasively.

PMID- 14658174
TI  - [Catastrophic antiphospholipid syndrome in the immediate puerperium].
AB  - We describe a female previously diagnosed of primary antiphospholipid antibody
      syndrome who presented a preclampsia in the second pregnancy. An urgent caesaria
      was made because of a worsening high blood pressure and oliguria. In the
      immediated puerperium she showed low platelets and persistent high blood
      pressure. Afterwards acute renal failure and neurological signs with a severe
      aortic valvulopathy were diagnosed. An haemolytic anemia was also detected.
      Definitive diagnosis was made by kidney biopsy with the result of a thrombotic
      microangiopathy. Treatment with low weight heparin and aspirin and systemic
      corticosteroids was started in the immediate puerperium and fresh frozen plasma
      was then added with a good response to treatment. Actually she is still with high
      blood pressure, aortic valvulopathy. Renal function is normal one year later.

PMID- 14658175
TI  - [Elevation of Creatine phosphokinase levels as marker of athero-embolic kidney
      disease].

PMID- 14658176
TI  - [Kidney hypoperfusion and overdose of metformin as cause of severe lactic
      acidosis].

PMID- 14658177
TI  - [Is "irreversible" the most appropriate term to substitute "terminal"? A second
      opinion].

PMID- 14658178
TI  - [Rhabdomyolysis, compartment syndrome and acute kidney failure related to cocaine
      consume].

PMID- 14658179
TI  - [Clinical analysis of 18 cases extranodal non-Hodgkin's lymphomas in head and
      neck].
AB  - OBJECTIVE: To analyze and discuss the clinical features, pathological
      classification, clinical stage, treatment and prognosis of head and neck non
      Hodgkin's lymphomas. METHOD: Of eighteen patients with head and neck non
      Hodgkin's lymphomas, seven patients received surgery, radiotherapy and
      chemotherapy, eleven patients received radiotherapy and chemotherapy. RESULT:
      Thirteen patients achieved complete remission(CR), five patients achieved partial
      remission(PR). Except one patient loosing to follow-up, seventeen patients had
      follow-up, ranging from three to five years. The seventeen patients all survived.
      CONCLUSION: Head and neck non-Hodgkin's lymphomas is difficult to right early
      diagnose. Radiotherapy and chemotherapy are the main treatment of it. Early using
      of radiotherapy and chemotherapy will make contribution to better prognosis.

PMID- 14658180
TI  - [Postoperative rupture of carotid artery in head and neck neoplasms].
AB  - OBJECTIVE: To explore the treatment of neoplasms in head and neck invaded the
      carotid artery. METHODS: Four cases with postoperative rupture of carotid artery
      invaded by the head and neck cancer were reviewed. The tumours were taken off
      from the carotid arteries and the carotid artery remained. RESULT: Rupture of
      carotid artery occurred in 4 patients within one week after radical neck
      dissection. One patient died because of its rupture again after repair. The other
      three survived after ligating the artery. CONCLUSION: The carotid artery involved
      by tumour of head and neck should be prepared for resection before operation. If
      the artery was obviously invaded by the tumour, both the tumour and artery should
      be resected together. Once the rupture of the artery occurred after operation,
      the artery must be ligated instead of being repaired.

PMID- 14658181
TI  - [Study on post-laryngectomy partial laryngeal defect repaired with omohyoid
      myofascial flap].
AB  - OBJECTIVE: To explore the clinical effect on defect of post-laryngectomy partial
      laryngeal repaired with omohyoid myofascial flap. METHOD: Twenty-four cases of
      supraglottic and glottic cancer were treated surgically. The tumors and involved
      cartilages were removed entirely. The omohyoid myofascial flap was utilized to
      repair the defects of larynx and reconstruct the glottis. For the cases of
      unilateral fixation of arytenoid, the arytenoids were removed and replaced by a
      piece of omohyoideus linked to hyoid bone, then were covered with mucous. The
      cases above T2 supraglottic and T3 glottic received radiotherapy. RESULT: The
      following-up time is 1-5 years. One case of supraglottic cancer(T3) dies from
      local recurrence after operation for 2 years and 9 months. One case of glottic
      cancer(T3) dies from neck and bone metastasis after operation for 4 years and 3
      months. Swallow function was preserved in all cases. The rate of deconnalation
      was 95.8%. 91.7% patients had laryngeal functions restored. CONCLUSION: For
      selected cases, using omohyoid myofascial flap to repair the partial laryngeal
      defect and reconstruct glottis is available and practicable.

PMID- 14658182
TI  - [An analysis of 30 cases skin flaps and muscular flaps transplanting for head and
      neck in the use of tissue defect repairing].
AB  - OBJECTIVE: To explore the effect of skin flaps and muscular flaps transplanted in
      the use of tissue defect repairing. METHOD: Thirty cases of tissue defect were
      repaired or reconstructed by forearm flaps, pectoralis major muculocutaneous
      flaps, frontal flaps, nasolabial fold flaps or paranavel rectus abdominis muscle
      flaps. RESULT: Twenty-nine cases were successful but one case was unsuccessful.
      CONCLUSION: Skin flaps and muscular flaps reconstruction are safe and reliable.
      But the indication should be selected and the complication should be prevented.

PMID- 14658183
TI  - [Surgical management of stomal recurrence].
AB  - OBJECTIVE: To study effective treatment of stomal recurrence. METHOD: Thirty-one
      patients with stomal recurrence underwent surgical management. Twelve of them
      considered to have the probability of metastasis to regional lymphnodes underwent
      modified radical neck dissection. Twenty-five cases(I and II type) received
      complete tumor excision, but for III and IV type, only 50% (3/6) of the patients
      gained complete tumor excision. The surgical defects were repaired by pectoralis
      major myocutaneous flap in all the patients. RESULT: In 13 cases of type I, 7
      cases had followed up for 3 years, 4 cases died, while in 12 cases of type II, 8
      cases had followed up for 3 years, 5 cases died. Survival remains poor for III or
      IV type. Most of them died within 3 years after operation. The complication rate
      of pharyngeal fistula and pneumatothorax was 12.9% and 9.7%, respectively.
      CONCLUSION: The overall prognosis of stomal recurrence is dismal. A proper
      surgical treatment in some cases will prolong the lifetime and improve their
      quality of life.

PMID- 14658184
TI  - [The clinical observation of early oral feeding following total laryngectomy].
AB  - OBJECTIVE: To demonstrate the feasibility of oral feeding 48-72 hours after total
      laryngectomy of carcinoma of the larynx or pyriform sinus. METHOD: Forty-two
      patients underwent total laryngectomy (included 34 patients of larynx carcinoma
      and 8 patients of pyriform sinus carcinoma) were random categorized into control
      group and experimental group. The experimental group of 21 patients who received
      oral feeding 48 to 72 h after total laryngectomy was compared with the control
      group of 21 patients who received oral feeding 10 to 12 days. RESULT:
      Pharyngocutaneous fistula occurred in one patient (4.8%) in the experimental
      group and in two patients (9.5%) in the control group. These differences were not
      statistically significant (P > 0.05). The length of hospital stay was
      significantly shorted. CONCLUSION: Our results indicate that in the patient
      population initiation of oral feeding 48 to 72 h after total laryngectomy of
      carcinoma of the larynx or pyriform sinus is a safe clinical practice.

PMID- 14658185
TI  - [Analyses of recurrences and nodal metastases of glottic carcinoma after
      operation].
AB  - OBJECTIVE: To study the feature and prevention of local recurrences and nodal
      metastases of glottic carcinoma after operation. METHOD: Seventy-six patients
      with glottic carcinoma were reviewed retrospectively. The relationship among the
      region involved by cancer, local recurrences, tumor stage and neck dissection was
      compared with multiple-factors stepwise regression. The relationship between the
      region involved by cancer and local recurrences was compared with chi-square
      test. RESULT: In this group of 76 patients with glottic carcinoma had been
      followed-up for 3 years, the 1-year and 3-year survival rate were 97.4% and
      92.1%. Eleven had occurred local recurrences and/or cervical lymph node
      metastases after operation. Six of thirty-five patients (17.1%) whose anterior
      commissure was involved had recurrences during the follow-up period. There were
      no local recurrences in another 41 patients. Three of twelve patients whose
      glottic tumors with subglottic extension (extension more than 5 mm below the
      glottiis) were found paratracheal lymph node (PTLN) metastases, one of which was
      lower jugular lymph node metastases. The glottic tumors with supraglottic
      extension or glottic tumors with subglottic extension which invaded less than 5
      mm weren't found PTLN metastases. By analysis of stepwise regression, it was
      found if there were the metastases of PTLN and lower jugular lymph node, the
      tumor often extend to the subglottic (P < 0.05). There is no difference between
      local recurrences and the tumor with or without involved anterior commissure (P >
      0.05). CONCLUSION: The glottic cancers with subglottic extension may occur PTLN
      and lower jugular lymph node metastases. The glottic cancers with involved
      anterior commissure are considered to be more at risk for local recurrences.

PMID- 14658186
TI  - [The study of the expression, effect and clinical relationship of TGF-beta 1 in
      the larynx squamous carcinoma].
AB  - OBJECTIVE: This study was to measure the expression of TGF-beta 1 in larynx
      squamous carcinoma, to investigate the relationship between TGF-beta 1 and
      pathological grading of tumours, the clinical staging and, through which the
      effect of TGF-beta 1 on the pathogenesis of the larynx squamous carcinoma was to
      be known. METHOD: RNA was extracted from the larynx squamous carcinoma tissues of
      21 patients and from normal laryngeal tissues of 15 cases. Reverse
      transcriptional polymerase chain reaction (RT-PCR) was applied to detect the
      expression of the TGF-beta 1 mRNA. RESULT: Ten of the 21 specimens of the larynx
      squamous carcinoma showed positive expression of TGF-beta 1 mRNA, then the
      expression ratio was 47.62%. The expression of TGF-beta 1 mRNA had relationship
      to the pathological grading and the clinical staging of the larynx carcinoma.
      CONCLUSION: TGF-beta 1 can be used as a marker to evaluate the progression of
      laryngeal squamous cell carcinoma.

PMID- 14658187
TI  - [Clinical study on oropharyngeal fatty infiltration on the pathogenesis of
      obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To detect the effect of lipid metabolism, fatty infiltration of
      oropharyngeal tissues in the subjects with obstructive sleep apnea syndrome
      (OSAS) and its pathogenesis. METHOD: Nineteen subjects in OSAS group and 9
      subjects in controlled group were chosen. The related clinical index including
      the size and weight of uvula in two groups were measured. Each composition of
      uvular tissue section (transverse section) in all subjects was measured by
      quantitative, morphometric image analysis technique. The uvular tissue sections
      were evaluated by light microscope (LM), 4 of them by transmission electron
      microscope (TEM). RESULT: 1. Subjects in OSAS group significantly had a greater
      body mass index, neck circumference, waist circumference, waist-to-hip
      circumference ratio (WHR), weight and size of uvula than those in controlled
      group. There were significant differences in TC, TG, LDL and TC/HDL between the
      two groups. 2. A significant difference in percentage of fat, muscle, fibrous
      tissue in uvula was also founded between the two groups. The serial tissue
      section of uvula in LM showed that there was excessive fatty infiltration that
      prominently founded in fibrous tissue and secondarily in muscle. And muscle
      fibers with partial atrophy and/or hypertrophy were prominent. We also detected
      that fibrous tissue and muscle fibers arranged in a disordered way. The uvula
      myofibril in TEM showed focal or spotted rough and deformity of Z line, sarcomere
      loss and vacuolation. Lipid droplet infiltration was also detected in adjoin of
      myofibril. 3. The degree of fatty infiltration of uvular tissue correlated with
      neck circumference, WHR, weight and size of uvula, TC and TC/HDL in two groups,
      and also had positive correlation with degree of OSAS recorded by AHI in OSAS
      group. CONCLUSION: The results suggested that lipid metabolic disorder might
      exist in subjects with OSAS. And abundant oropharyneal fatty infiltration might
      be an important role in pathogenesis of OSAS that possibly contributed to change
      the size and shape of pharyngeal airway and compliance of pharyngeal wall.

PMID- 14658188
TI  - [Reevaluation of the indications for tracheotomy in patients with OSAHS in
      perioperative period].
AB  - OBJECTIVE: To reevaluation of the indications for tracheotomy in patients with
      OSAHS during perioperative period. METHOD: Sixty-eight of 89 patients were severe
      OSAHS diagnosed with PSG. Perioperative management was taken out, including
      preoperative rediagnosis, CPAP treatment, treatment of medical complications,
      confirming the excision area in operation, using steroids to ease postoperative
      edema, and so on. RESULT: The mean minimum oxygen saturation of 51 patients
      received preoperative CPAP treatment was increased from (63.54 +/- 9.45)% to
      (83.32 +/- 8.85)% (t = 11.52, P < 0.01), and only one of them underwent
      tracheotomy because of severe fat. But two of 17 patients not received
      preoperative CPAP treatment underwent tracheotomy. No severe upper airway
      complications occurred. CONCLUSION: Intensive perioperative treatment can avoid
      tracheotomy in patients with severe OSAHS during perioperative period.

PMID- 14658189
TI  - [Central suspension operation of hyoid and lower jaw for OSAS].
AB  - OBJECTIVE: To evaluate the prospective effect and minimize the postoperative
      trauma of applying the central suspension operation of hyoid and lower jaw for
      the treatment for OSAS in 28 cases. METHOD: The data of 28 patients with
      obstructive sleep apnea syndrome(OSAS) operated with central suspension operation
      of hyoid and lower jaw and uvulopalatopharyngoplasty(UPPP) were analyzed. RESULT:
      One case (3.6%) reported unchanged snoring and apnea and hyponea index. Twenty
      seven cases (96.4%) improved after the operation for at least 6 months to 3
      years. The complications include tonsil bleeding (1 case), suffocation after
      extraction of endotracheal tube (1 case), temporal tongue insufficiency (1 case).
      CONCLUSION: On the previous basis of UPPP, we emphasize the protection of pharynx
      muscles and adjusting the position. The central suspension operation of hyoid and
      lower jaw not only increases the curative effect in the long run, but also avoids
      the tracheotomy.

PMID- 14658190
TI  - [The study on the expression of tumor-suppressor gene p15 and Rb in laryngeal
      squamous cell carcinomas].
AB  - OBJECTIVE: To study the clinical significance of p15 and Rb protein expressions
      in laryngeal squamous cell carcinomas (LSCC). METHOD: p15 and Rb proteins were
      examined with immunohistochemical SABC method in the paraffin-embedded specimens
      of 45 cases with LSCC and 15 cases of laryngeal normal or proliferative mucosas
      of larynx as a contrast. RESULT: The positive rate of p15 protein in the cases of
      LSCC is 48.9%, while the positive rate in the other group is 100%. The difference
      is significant. The positive rate of p15 protein is 66.7% in the group of LSCC
      during 0-II phases, and in the other group of LSCC during III-IV phases, the
      positive rate is 33.3%. The difference is significant. The positive rate of Rb
      protein in the cases of LSCC is 88.9%, the positive rate in the other group as a
      contrast is 93.3%, the difference between two groups isn't significant. Analyzed
      by chi-square test, p15 protein expressions don't correlate with Rb protein
      expressions in the cases of LSCC. Rb protein expressed apparently positiveness in
      the basal cells and adjacent stratum spinosum cells of laryngeal stratified
      squamous epithelium, while p15 protein expressed apparently positiveness in the
      distant stratum spinosum cells and stratum granulosum cells. CONCLUSION: Tumor
      suppressor gene p15 may play an important role in the genesis and development of
      LSCC. The analysis of p15 protein expression may provide evidence for the
      therapeutics and evaluate prognosis of LSCC. p15 and Rb proteins aren't parallel
      in each stratum of the laryngeal normal or proliferative stratified squamous
      epithelium. p15 protein plays an important role in cell proliferation.

PMID- 14658191
TI  - [Mycosis of the tonsil].
AB  - OBJECTIVE: To evaluate the early diagnosis ways of the tonsil mycosis. METHOD:
      The study was designed to investigate 18 patients with mycosis of tonsil in the
      PUMC hospital since 1995 year. Direct smear and microscopical examination of
      secretory material, tissues from tonsil infection were conducted; fungus culture
      was performed in the fungi positive cases for microscopical identification.
      RESULT: The diagnosis of all patients were demonstrated by the pathogeny check at
      last. CONCLUSION: The direct smear examination and fungus culture are important
      methods for early diagnosis to the mycosis of tonsil.

PMID- 14658192
TI  - [The relationship between the density of house dust mite allergens in bedroom and
      the attacks of allergic rhinitis].
AB  - OBJECTIVE: To investigate the relationship between the density of house dust
      mites allergens in bedroom and the attacks of allergic rhinitis in patients
      sensitive to mite. METHOD: Seventy-five houses (35 patients with allergic
      rhinitis and 30 healthy controls) were visited for dust sampling from mattresses,
      sofas, beddings and pillows. Der p1 and Der f1 levels were measured by ELISAs.
      RESULT: Der p1 and Der f1 levels in healthy control group were significantly
      higher than levels in patient group(P < 0.05). CONCLUSION: The amount of mite
      allergens might not be the determining factor for allergic rhinitis
      sensitization.

PMID- 14658193
TI  - [Four cases of primary neuroendocrine carcinoma in ear, nose, pharynx and
      larynx].
AB  - OBJECTIVE: To discuss the clinical pathologic features and therapeutic method of
      the primary neuroendocrine carcinoma in ear, nose, pharynx, larynx. METHOD: One
      case of atypical carcinoid tumor in larynx is treated by epiglottidectomy. One
      case of atypical carcinoid tumor in rhinopharynx is treated by radiotherapy. One
      case of typical carcinoid tumor in middle ear is treated by exploratory incision
      and radical mastoidectomy. One case of small cell neuroendocrine carcinoma in
      right nasal cavity is treated by resection and radiotherapy. RESULT: The patient
      of atypical carcinoid tumor in larynx died after 5 years and the patient of
      atypical carcinoid tumor in rhinopharynx died after 1 year. The patient of
      typical carcinoid tumor in middle ear was followed-up 3 years and the patient of
      small cell neuroendocrine carcinoma in right nasal cavity was followed-up 2
      years, and the carcinomas didn't recrudesce. CONCLUSION: The primary
      neuroendocrine carcinoma in ear, nose, pharynx, larynx is classified in three
      states: typical carcinoid tumor, atypical carcinoid tumor and small cell
      neuroendocrine carcinoma. Typical carcinoid tumor is a kind of low malignant
      tumor and small cell neuroendocrine carcinoma is a kind of high malignant tumor
      and atypical carcinoid tumor is a kind of medium malignant tumor. The chief
      therapeutic method of the primary neuroendocrine carcinoma in ear, nose, pharynx,
      larynx is surgical intervention.

PMID- 14658195
TI  - [An study on functioning remobilization of the paralyzed vocal cord by latero
      terminal neurorrhaphy in rats].
AB  - OBJECTIVE: To investigate the effect and the clinic value of latero-terminal
      neurorrhaphy to treat vocal cord paralysis. METHOD: Sixty SD rats were divided
      into three groups. In the experimental group, the right recurrent laryngeal
      nerve(RLN) was incised and anastomosed to the right phren nerve by means of
      latero-terminal neurorrhaphy. The internal nerve of the right RLN was incised and
      anastomosed to the right ansa cervicals nerve by end-to-end nerve anastomosis. In
      control group, the right RLN was incised and sutured to the right phren nerve by
      end-to-end nerve anastomosis. The internal nerve of the right RLN were incised
      and anastomosed to the right ansa cervicals nerve by end-to-end nerve
      anastomosis. In normal group rats, the nerves were only exposed. One to three
      months later, 10 rats from each group were examined for vocal cord movement and
      nerve regeneration by using fibrolaryngscope and nerve electromyography. RESULT:
      One months after operation. This effect of latero-terminal neurorrhaphy had
      significant difference compared with the control group (P < 0.05). Three months
      after operation. This effect of latero-terminal neurorrhaphy had not significant
      difference compared with the control group (P > 0.05). CONCLUSION: The latero
      terminal neurorrhaphy has a similar treatment effect compared with end-to-end
      nerve anastomosis. This microsurgical technique provides a new method for
      treating vocal cord paralysis.

PMID- 14658194
TI  - [The electro-physiological change of guinea pig cochlea caused by intracochlear
      perfusion of sodium salicylate].
AB  - OBJECTIVE: To investigate the way how sodium salicylate affects cochlear function
      and discuss its possible mechanism. METHOD: Sodium salicylate was perfused
      through guinea pig cochlea. The thresholds and input-output (I/O) functions of
      compound action potential (CAP) and summating potential (SP) were monitored
      during the perfusion. RESULT: Sodium salicylate caused a significant change of
      CAP and SP threshold as well as I/O curve. The relationship between CAP and SP
      threshold change at 10 kHz during perfusion with 10 mmol/L salicylate tends to be
      1:1. CONCLUSION: Outer hair cells are most likely to be the sites of action of
      sodium salicylate and this action on the outer hair cell active process might
      lead to its ototoxicity.

PMID- 14658196
TI  - Palliative care: the legal & regulatory requirements.
AB  - While following the same approach to care as hospice, palliative care reaches
      patients who do not necessarily have a terminal diagnosis or a life-threatening
      illness, and/or are seeking curative treatment. Reimbursement methodologies and
      requirements for palliative care differ from hospice, and are not explicitly
      covered by federal and state regulations. In the first article of a two-part
      series, the author reviews licensing issues, reimbursement requirements, fraud
      and abuse pitfalls, and cost report requirements for home health agency
      palliative care programs.

PMID- 14658197
TI  - Clinical care & finance: can this marriage be saved?
AB  - Financial staff and clinical staff do not necessarily see eye-to-eye. However,
      mutual understanding of one another's areas of expertise is essential to the
      success of a hospice. Financial and clinical staff can work together to
      streamline employee reporting, such as on time sheets and during annual reviews,
      to ensure that important data is being collected and staff don't waste time
      reporting on and analyzing extraneous data.

PMID- 14658199
TI  - The role of the psychiatric nurse in a home care palliative care program.
AB  - The psychiatric nurse can play a vital role on a palliative care team.
      Psychiatric nurses can work with patients to sort out the intense and conflicting
      feelings that affect patients and their families facing terminal illness and
      death. Patients can be guided through "life reviews," or nurses can craft
      interventions to reduce patient anxiety, assist with pain management, or promote
      physical and psychological comfort.

PMID- 14658198
TI  - Impacting family satisfaction with hospice care.
AB  - Family satisfaction is one of the most important outcomes for hospice care. A
      survey conducted in 2001 by Press Ganey Associates found overall high levels of
      family satisfaction with hospice care, but also highlighted areas needing
      improvement. Hospices need to pay more attention to ancillary care services,
      logistical issues, and the problem of late-timed referrals.

PMID- 14658200
TI  - Pursuit of happiness as the CEO: the business of doing hospice business.
AB  - The growth of hospice over the past 20 years has been rapid. Hospices have
      expanded staff and expanded services to meet increasing demand and a greater
      variety of patients. Hospice CEOs have had to spearhead these changes. This
      article presents the challenges that one hospice CEO has faced over her 20-year
      career.

PMID- 14658201
TI  - Can we be connected while remaining separate? Forging partnerships between all
      volunteer & Medicare-certified hospices.
AB  - When the Medicare hospice benefit was enacted 20 years ago, many hospices greeted
      the news with great relief. This benefit helped many fledgling hospices start up
      and survive. However, a group of hospices realized that some of the people for
      whom they previously cared were not eligible for services under the Medicare
      hospice benefit. Thus, volunteer hospices filled that need, supporting and
      advocating for people who did not fit the hospice benefit criteria, but who
      wanted hospice support. Since volunteer hospices and Medicare-certified hospices
      play two very different roles in the hospice care delivery system, there are many
      opportunities for the two types of hospices to partner to meet patient care
      needs.

PMID- 14658202
TI  - The silent crisis: women and the need for long-term care insurance. Part 2.
AB  - As the number of people living longer increases and the proportion of women to
      men in the older age brackets grows larger, the imbalance between economic and
      social factors also increases. Women make up greater numbers of nursing home and
      assisted living facility residents, and must impoverish themselves to qualify for
      Medicaid assistance to remain in these facilities. Women also make up the
      majority of caregivers for elderly parents remaining at home, causing physical,
      mental, and emotional stress, in addition to affecting their working lives and
      earning potential. These economic and physical stressors are the subject of the
      second part of a three-part examination of women's need for long-term care
      insurance.

PMID- 14658204
TI  - The importance of screening for depression in home care patients.
AB  - The home care population is especially vulnerable to depression, yet a recent
      study showed that home care nurses are not well equipped to identify the signs
      and symptoms of depression (Brown et al., 2003). Probable causes include lack of
      training and support for home care nurses combined with passivity and
      embarrassment about depression among elderly patients. Depression is treatable;
      however, when left undiagnosed it causes patient suffering, increased likelihood
      of adverse events, and higher medical costs. Home care agencies can support their
      nurses to better recognize the signs and symptoms of depression through education
      and increased awareness of the prevalence and complexity of depression in the
      home care population. Furthermore, with the aid of screening questions already
      included in the Outcome and Assessment Information Set (OASIS), agencies can
      identify patients at risk of depression and refer them to necessary and
      beneficial mental health services.

PMID- 14658205
TI  - When the end of life is the beginning of something beautiful.

PMID- 14658207
TI  - When force is necessary.

PMID- 14658208
TI  - A drug- and alcohol-free workplace.

PMID- 14658209
TI  - Gut feeling.
AB  - An aneurysm is an abnormal dilatation of an artery, often as a result of
      atherosclerotic disease. Hypertension, connective-tissue disease and a family
      history of aneurysms are predisposing risk factors. They may occur at any point
      in the vasculature from the aortic root to distal peripheral vessels, but they
      are most common in the abdominal aorta. Many times they are asymptomatic and
      undiagnosed, but as they progressively enlarge, they may compress on surrounding
      structures, release atherosclerotic debris or thrombi and possibly rupture.
      Aneurysms occur in approximately 3% of people older than 50; some of these do not
      rupture. An aneurysm is not typically painful until it dissects or ruptures.
      [table: see text] The abdominal aorta splits at the level of the umbilicus, so
      the abdomen must be palpated above the level of the umbilicus to feel for aortic
      enlargement. Obese patients make detection more difficult, as the presence of a
      pulsatile mass may be covered. An aneurysm will still conduct blood flow into the
      lower extremities, so pulses will not be compromised, and capillary refill and
      temperature will be normal. An acute rupture is a catastrophic event
      characterized by poor perfusion or frank shock and pain in the abdomen, back or
      groin. Accompanying symptoms may include a pulsatile abdominal mass, absence of
      distal pulses, and radiating pain into the lower back that is often described as
      "tearing" or "ripping." The risk of rupture has a direct correlation with an
      aneurysm's size. Generally, elective surgery is considered with an abdominal
      aneurysm larger than 4.5 centimeters, but there are many factors which may
      preclude repair. Non-surgical treatment of an aneurysm has been performed by
      percutaneously placing a prosthetic graft at the site, anchoring the graft above
      and below the aneurysm, thereby isolating the aneurysm from the circulation.
      Surgical treatment for elective repair of an aneurysm that is not ruptured is
      still very difficult and has a significant risk of complications. A ruptured
      abdominal aortic aneurysm has a very high incidence of mortality. Early
      identification and rapid transport to a facility with vascular surgery services
      are the keys to survival. This case demonstrates early recognition by the EMS
      crew and successful resuscitation from a cardiac arrest due to profound shock. In
      other cases, EMS providers may have the first and only opportunity to recognize a
      ruptured aneurysm and direct the ED and surgical teams to the cause of sudden
      shock or cardiac arrest.

PMID- 14658210
TI  - Back to basics. What I'd like to see.

PMID- 14658211
TI  - Strategic documentation: a key for survival in the HIPAA era.

PMID- 14658212
TI  - Documenting your life away: common EMS report errors.

PMID- 14658213
TI  - To have and to hold, until competence do us part!
AB  - By using the EMS "tools" discussed here, your exposure to mismanagement of
      patients who refuse treatment/transport can be greatly mitigated, but probably
      not completely eliminated. Remember, an EMS provider may be the last medical
      professional to see a patient alive before he refused transportation. It is
      suggested that EMS providers research their own local and state laws concerning
      patient refusal, as these laws vary from state to state. At a bare minimum, your
      refusal policy must address the high-risk refusals that trigger medical
      oversight, some method for determining patient competence, and a documentation
      policy with post-review that supports a well-constructed account of the refusal.
      As for the chest pain patient discussed earlier. If this patient can be
      determined "competent" regardless of his cardiac stability and etiology, he can
      refuse treatment and transportation. The EMS provider's protocols should address
      the use of MMSE and OLMC consultation. The OLMC consult should involve a
      conversation with both the patient and his wife, who would add credibility to her
      husband's competence and could possibly be used as a source of support for EMS.
      If determined competent, the risks of refusing treatment and transportation would
      be discussed on the radio, including the patient's possible death. The patient
      would be advised of the benefits of transportation, including the proposed EMS
      care and ensuing treatment at the hospital. If not convinced, the patient could
      sign an informed refusal, witnessed by his wife or another third party. The
      patient and his wife would be advised to call 9-1-1 if the chest pain returns.

PMID- 14658214
TI  - Alternatives to Mac and Miller for managing the difficult airway.
AB  - EMS providers should be familiar with and well practiced in a variety of
      available intubation techniques, so that when an airway problem occurs, it can be
      managed. However, with the rapid advancements in airway management technology,
      many EMS providers have not had an opportunity to use the equipment in real
      patient situations. Acquiring the equipment is often not the problem; learning to
      use it and retaining these skills may be the long-term issues. Participating in
      specialized airway courses and workshops is an excellent means of introducing the
      manual skills required to implement airway devices, but practice on manikins does
      not accurately simulate "real" patient situations and therefore is often not
      directly applicable. EMS organizations and educational facilities must provide
      learning opportunities to implement new airway technologies and skills.

PMID- 14658215
TI  - Hypertension: an overview for prehospital care providers.

PMID- 14658216
TI  - Helping hands: consultants in the ambulance industry.

PMID- 14658217
TI  - Fixing a hole: information security for emergency response agencies. Inteerview
      by John Erich.

PMID- 14658218
TI  - Personnel safety.

PMID- 14658219
TI  - Ambulance A & P. How do your brakes work?

PMID- 14658221
TI  - [Anti-DNA antibodies: structure and pathogenic role].
AB  - Anti DNA antibodies are generally classified into two major groups: Anti ds DNA
      (anti double .. stranded DNA) antibody and anti ss-DNA (anti single-stranded DNA)
      antibody. Anti-ds DNA antibodies are highly specific to systemic lupus
      erythematosus (SLE) and are probably involved in the pathogenesis of lupus
      nephritis. There are numerous serological tests for detecting anti-ds DNA. The
      detection of anti-ds DNA antibodies in the circulation of patients is one of the
      major criteria for the diagnosis of SLE; moreover, exacerbation of the disease
      are proceeded by increasing anti-DNA levels and the development of lupus
      nephritis, one of the most serious complications of the disease, strongly
      correlates with the presence of high avidity anti-DNA. It was reported that even
      normal individuals express anti-ds DNA. However, anti ds DNA found in healthy
      individuals is usually of the immunoglobulin M (IgM) isotype and shows a low
      affinity to ds-DNA. These natural antibodies are characterized by a wide cross
      reactivity and are usually encoded by gene segments in the germ line
      configuration. In contrast, the ds-DNA antibodies involved influenced by various
      findings supporting the proposition that anti-ds DNA is involved in the
      pathogenesis of SLE, an enormous amount of scientific investigation has failed to
      reveal the exact mechanism through which this occurs.

PMID- 14658222
TI  - [Mutational analysis of breast/ovarian cancer hereditary predisposition gene
      BRCA1 in Tunisian women].
AB  - BRCA1 is a breast cancer susceptibility gene. Germline mutations in BRCA1 gene
      are found in 5 to 10% of breast cancer. The aim of this study is to screen the
      tunisian women with familial or sporadic breast cancer for BRCA1 gene mutations.
      The authors used the Protein Truncation Test (PTT) and DNA sequencing to detect
      BRCA1 gene mutations in 12 tunisian families with breast cancer and the Allele
      Specific Oligonucleotide-PCR (ASO-PCR) to detect the 185delAG and 1294del40
      mutations in 150 tunisian women with sporadic breast cancer. A nonsens mutation
      was found, by PTT, in exon 11 of BRCA1 gene in one case of familial breast
      cancer. No mutation in the rest of exons was found by the DNA sequencing. The
      BRCA1 1294del40 mutation was found only in a patient with non familial breast
      cancer. The 185delAG mutation was absent in all cases of breast cancer. These
      data suggest that the germline mutation of BRCA1 is implicated in breast cancer
      in Tunisia and that the 185delAG mutation is absent in arab tunisian women.

PMID- 14658223
TI  - Deafness genes and the mechanism of hearing.
AB  - Over the past few years, significant progress has been made in the understanding
      of the hearing mechanism. The identification of genes involved in deafness has
      begun and is now progressing rapidly. To date, at least 36 genes are known and
      exploration of their functions has already begun. Indeed, cloning deafness genes
      is only the first step towards the understanding of the hearing process.

PMID- 14658224
TI  - Analysis of heat shock protein polymorphisms in a large family with autoimmune
      thyroid diseases.
AB  - Graves disease and Hashimoto's thyroiditis are autoimmune thyroid diseases (AITD)
      in which the genetic contribution is complex. The purpose of this work was to
      analyze the influence of hsp70 gene polymorphisms on the susceptibility to AITD.
      The hsp 70-2 and hsp 70-hom polymorphism was analyzed, by PCR-RFLP using PstI and
      NcoI enzymes, respectively, in 40 patients affected with AITD and 38 related
      healthy individuals belonging to a large consanguineous family named Akr. The
      transmission disequilibrium test (TDT) was applied on nuclear families, deduced
      from the Akr pedigree, with at least one heterozygous parent for each studied
      polymorphism. The corresponding x2 values for hsp 70-2 and hsp 70-hom were,
      respectively, of 0.52, p > 0.05 and 2.77, p > 0.05. Our data indicated lack of
      association between these hsp polymorphisms and AITD in this large family.

PMID- 14658225
TI  - [Linkage analysis for complex diseases: a new life for an old method].
AB  - In this paper, I present the main approaches used in gene mapping of complex
      human diseases by linkage analysis based on molecular markers. The first section
      describes the traditional LOD-score analysis and gives a review of different
      improvements and refinements of this approach, which has been proposed in order
      to take into account complicating factors such as incomplete penetrance, genetic
      heterogeneity and unknown mode of inheritance. The second section describes the
      three main approaches of non-parametric linkage analysis, for which there is no
      need to specify a genetic model (mode of inheritance, allele frequencies, ..). A
      comparison between these three methods, which may seem to be more appropriate for
      complex diseases, is given based on the most recent published studies. In the
      third section and discussion, I compare the LOD-score and non-parametric methods
      by stressing the advantages and drawbacks of each approach as found in recent
      publications. I deduce that, in spite of its apparent and assumed
      inappropriateness to the analysis of complex diseases, the LOD-score method is
      still very useful and could provide, in some circumstances, more power and
      precision than model-free methods.

PMID- 14658226
TI  - Leishmania infantum species-specific kDNA probes: isolation and evaluation.
AB  - The study refers to the isolation of specific DNA probes to the parasite species
      Leishmania (L) infantum according to different strategies using recombinant
      minicircles isolated from L. infantum kinetoplast DNAs. A first probe was
      identified following a classical procedure. One mini-circle selected for strong
      reactivity to L. infantum total DNA was used to identify specific subfragments to
      this species among which the 95bp fragment, 3B8HaeIII-2 was selected. For the
      obtention of the second probe, a strategy based on sequential screenings for
      specificity and sensitivity was applied. This allowed identification of a set of
      minicircles showing an increased specificity to L. infantum as compared to other
      species, and an increased sensitivity of reaction as compared to the other
      minicircles. Subclonings and screenings allowed a final selection of a 137bp
      minicircle fragment: 3E9HaeIII-12. Reactivities of the 2 probes were assessed on
      a panel of total DNAs and promastigotes from 74 isolates pertaining to 9 species
      encountered in the Old World. Parasites isolated in Tunisia from different foci,
      different hosts after different transmission seasons were included.
      Hybridizations have shown the exquisite specificity of these probes to L.
      infantum in this country. Probe 3E9HaeIII-12 was found to be the more sensitive
      where down to 10 ng of total DNA and 10(3) promastigotes could be detected. From
      this study and as compared to data provided in the literature, the second
      procedure allowed at least 10-fold increase in sensitivity.

PMID- 14658227
TI  - Leishmania major induces deactivation of extracellular signal regulated kinases 2
      in human U937 macrophage like cells.
AB  - The protozoan parasite of the genus Leishmania has developed strategies to evade
      host defence mechanisms. Leishmania (L.) parasites interfere with several
      signalling pathways to inhibit phagocyte functions. In the present study, we
      analysed possible alteration of MAPK activation during infection of human U937
      cell line with Leishmania major parasites. Analysis of whole cell lysates by anti
      phosphotyrosine immunoblotting, showed that the pattern of tyrosine
      phosphorylated proteins were different for undifferentiated, PMA differentiated
      and Leishmania major infected cells. Cell infection induces a decrease in
      tyrosine phosphorylation of several host cell proteins, including PMA-induced
      tyrosine phosphorylated proteins. Leishmania major also caused a time dependent
      inhibition of ERK2 phosphorylation which correlates with the inhibition of ERK
      activity. This Leishmania induced effect was blocked when the cells were treated
      with a PTP inhibitor, prior to infection. These results suggest that Leishmania
      major may interfere with MAPK mediated signal transduction of the host cell
      through the inhibition of ERK2 activation and that this effect may be mediated by
      induction of protein tyrosine phosphatases activities.

PMID- 14658228
TI  - [Parasitoses and immunodepression].
AB  - The immunodepression, related or not to AIDS, induces the emergence of
      opportunistic parasitosis and mycosis. Our objective is to analyze these
      pathogenic agents, their clinical expression and gravity in immunocompromised
      individuals. Our retrospective 9 years study reported parasitic and fungic
      infections complicating immunodepression. Among 31 HIV infected patients, we
      diagnosed the following parasitosis: Cryptosporidium (7 cases), Isospora belli (2
      cases) and Enterocytozoon bieneusi (1 case). Pulmonary pneumocystosis was
      diagnosed in 6 cases, cerebral toxoplasmosis in 6 cases and meningo-cerebral
      cryptococcosis in 1 case. The systemic candidasis was diagnosed in 13 leukaemic
      patients. The intestinal anguilluliasis was found in 5 patients treated with
      corticoids for long periods. A case of Kala azar was observed in a 83 years man
      treated with corticoids. A disseminated aspergillosis occurred in a child with a
      Chediack Higashi syndrome. A gingivo-labial fusariosis was diagnosed in a
      leukaemic patient. This emergency of the new parasitic and fungal agents requires
      a better understanding of these affections in order to improve their early
      diagnosis and treatments.

PMID- 14658229
TI  - Genomic structure and characterisation of the promoter region of the human IL-18
      gene.
AB  - Interleukin (IL)-18 is a cytokine that plays an important role in the T helper
      (Th) 1 response, primarily by its ability to induce gamma interferon (IFN-gamma)
      production by T cells and Natural Killer (NK) cells. It also plays a role in host
      resistance to infection and in Lipopolysaccharides (LPS)-induced histopathology.
      By a direct sequencing on P1 Artificial Chromosomes (PAC) clones, we have
      determined the genomic structure and the promoter region of the human IL-18 gene.
      The IL-18 gene spans approximately 20 Kb and consists of 6 exous. The 5'-flanking
      regions of human IL-18 and mouse IL-18 show 75% homology suggesting conserved
      promoter regulatory factors.

PMID- 14658230
TI  - [Production of avian infectious bursitis virus by in vivo DNA genomic
      transcription].
AB  - Generation of infectious particles of infectious bursal disease virus (IBDV) has
      been essentially performed by transfecting susceptible cells with in vitro
      synthesized cRNAs of genomic segments A and B. In the present study, we have
      explored the possibility to proceed directly in vivo without taking into account
      the extra-genomic vector-derived sequences. For this purpose, cDNAs of segments A
      and B were subcloned into an eucaryotic expression vector under the control of
      the immediate early CMV promoter. Upon transfection of primary culture of chicken
      embryonic fibroblasts with both constructs, a cytopathic effect (CPE) typical of
      that produced by IBDV could be observed, indicating that the 5'- and 3'- vector
      derived extra-nucleotides did not interfere with the replication and packaging
      process. Finally, in order to develop a GFP-based packaging assay, we first tried
      to express this fluorescent protein in the context of the IBDV polyprotein
      encoded by the genomic segment A. Our initial results indicate that the presence
      of IBDV specific sequences upstream of the GFP polypeptide dramatically decreased
      the fluorescence of the latter protein.

PMID- 14658231
TI  - [Characterization of a Cl. Perfringens type D strain, isolated in the field and
      optimization of epsilon toxin biosynthesis in a cell culture].
AB  - A field strain of cl. perfringens, named Dt001, was isolated from kidney of ovine
      enterotoemia case. The isolate characterized as Cl. perfringens, type D was based
      on its cultural and biochemical characters and its factors of virulence. The
      strain was very toxinogenic and well adapted to culture conditions of
      biofermentation when the parameters related to ptt, incubation time, substrat ...
      were optimized. Thus, the use of carbon source as polymer (destrine), the
      continuous control of pH allowed improvement of the rate of biosynthesis of
      Epsilon toxine by 10 times. The study of the immunogenicity of the isolate showed
      that preparations of anacultures were more immunogenic then those of anatoxine
      type. The fact that the two forms of epsilon antigens (protoxin and active toxin)
      show similar immune response in rabbits, indicates that the proteolytic action of
      trypsin is limited only to the toxic sites and does not affect the immunogenic
      epsitopes of the toxin. It also suggests a molecular organization of epsilon
      toxin in which the immunogenic epsitopes and the toxin sites are apart. The
      biotechnological performances and the immunogenicity and toxinogenical of the
      Dt001 isolate are in favor of its possible use as a component of an inactivated
      vaccine against enterotoxenia.

PMID- 14658232
TI  - [Are there health risks for travel among Tunisians? What type of medical care
      should be assured?].
AB  - The present work aims to assess the importance of the international travels of
      Tunisians, their destinations, the risks they face as well as the means to reduce
      them. Therefore, data related to the period from 1989 to 1998, were collected
      from official organisms involved in this area. Results revealed an increase of
      the number of Tunisians travelling outside the country of 23% between 1989 and
      1998, with a mean progress of 5.7% per year since 1993. Main destinations were
      Maghrebin countries (65.7%), Europe (30%) and Middle East (4%). The number of
      persons leaving to high risk destinations remains difficult to assess and shows
      the importance of implementing a surveillance system to insure an adequate
      medical follow-up of this category of travellers. The structures actually
      involved in the health management of Tunisian travellers have a weak recruitment
      which demonstrates the importance to strengthen the sensitization of general
      practitioners to this subject and the promotion of the immunization ward of
      "Institut Pasteur" to a national centre of travelling medicine.

PMID- 14658233
TI  - [Evaluation of two DNA probes specific for Leishmania infantum in the diagnosis
      of canine leishmaniasis].
AB  - This study reports on the evaluation of two L. infantum specific DNA probes for
      the diagnosis of canine leishmaniasis. The probes presented very satisfying
      performances in terms of specificity (100%) and predictive value of the positive
      result (100%). However, their sensitivity (35.3%) and the clinical complexity of
      canine infections render their use difficult in epidemiological surveys of
      visceral leishmaniasis aiming at measuring the prevalence of the dog infection by
      L. infantum. The sensitivity of these tools has improved (66.7%) when dogs
      presenting patent leishmaniasis were considered. Such probes constitute
      appropriate tools to confirm suspected cases of leishmaniasis. Unlike the
      classical parasitological and serological tools, this kind of tools allows a
      concomitant detection and identification of the causative agent. Therefore,
      despite their low sensitivity, these probes can still be of importance in
      epidemiological investigations.

PMID- 14658234
TI  - [Concordance of leishmaniasis cutaneous tests in Tunisia].
AB  - A cross sectional study aimed to evaluate the effect of antigenic preparation
      (Leishmania infantum versus Leishmania major) and dose of leishmania antigens (5
      x 10(6) versus 2.5 x 10(6) parasites in the same volume) on the reproducibility
      of delayed type hypersensitivity leishmania skin test. Results showed that among
      34 individuals involved from visceral leishmaniasis endemic area. 26 (76.5%) had
      a positif Leishmania infantum leishmania (L-L. infantum) test and 27 (79.4%) to
      Leishmania major leishmania (L-L. major). Mean size of cutaneous reaction was
      5.94 +/- 2.86 mm for L-L. infantum and 5.41 +/- 3.23 mm for L-L. major, with a
      significant positive linear association (p < 10-3). Intra-class correlation
      coefficient was 0.80 (CI95% = [0.64-0.93]) and concordance Kappa (kappa) was 0.57
      (CI95% = [0.40-0.74]). Among 153 individuals from zoonotic cutaneous
      leishmaniasis. 92.9% revealed a positive test for both types of leishmanin (L-L.
      major full dose versus L-L. major half dose). Mean size of cutaneous reaction was
      12.61 +/- 4.65 mm for the reference test and 11.30 +/- 3.95 mm for diluted one,
      with a positive linear association (p < 10-3). Intra-class correlation
      coefficient was 0.78 (IC95% = [0.71-0.84]) and concordance Kappa (kappa) was 0.82
      (IC95% = [0.73-0.91]). These results demonstrate a limited effect of leishmania
      antigenic variation and antigen dose on the reproducibility of delayed type
      hypersensitivity induced by the leishmanin test.

PMID- 14658235
TI  - [Study of the protective capacity of scorpion venom Buthus occitanus tunetanus
      polymerised to glutaraldehyde in mice strains with different haplotypes].
AB  - The immune response obtained against the toxic fraction of the scorpion venom
      Buthus occitanus tunetanus detoxified by polymerisation with glutaraldehyde, was
      analysed for low inbred mice having different haplotypes: C57BL/6 (H-2b) et
      BALB/c (H-2d) and the SWISS outbred mouse. This three strains of mice, immunized
      with the polymeric form of Bot-G50 are able to induce an immune response with
      bumoral mediation. The anti-polymers antibodies obtained from immunized mice,
      cross-react with the native Bot-G50 fraction. Indeed, in vitro protection
      experiments demonstrated that immune sera were neutralizing (between 150 and 235
      micrograms of Bot-G50 ml). The in vivo protection assays showed that immunized
      mice could resist the challenge by high amount of toxic fraction (between 70 and
      80 micrograms of Bot-G50). This protection was found to be long-lived, since
      immunized SWISS mice could resist the challenge by 4 DL50 of the toxic fraction
      (80 micrograms) six month after the start of the immunized program.

PMID- 14658236
TI  - [Delay and characteristics of scorpion bite management in the Sidi-Bouzid
      region].
AB  - Scorpion envenomation represents a potential danger in the 2/3 of Tunisia's
      territory but Sidi Bouzid area is the most infected with 1/6 of the piqued in
      Tunisia. The purpose of the study was to assess the result of a program for
      scorpion control in Sidi Bouzid and especially the delay from being stung to
      access to health care service. The analysis of data related to program shows that
      the delay was decreased only in 4 districts out of 11. This situation should be
      explained by such factors as information and behaviour of population, access to
      health care.... It is necessary to increase the action recommended by the program
      and to behold specific characteristics of each district.

PMID- 14658237
TI  - [Probable origin of the Robertsonian phenomena in domestic mice in Tunisia].
AB  - The Robertsonian phenomenon in house mice (Mus musculus domesticus) from Tunisia
      consists in the presence of only one 22-chromosome Robertsonian race (22Rb)
      carrying the maximum number of fusions observed until now. The 22Rb populations
      exclusively occupy urban centers in the Eastern-Central region of Tunisia where
      standard population with 40-all acrocentric chromosomes (40Std) occur in
      surrounding neighborhoods and rural environments. In addition to the habitat
      partition, allozyme and mitochondrial DNA analyses showed that the 22Rb
      populations were genetically differentiated from the 40Std ones. This
      differentiation mostly stemmed from an important decrease in genetic variability
      in the 22Rb populations from the Sahel towns. The extent of morphological,
      ecological and genetical divergence observed between these chromosomal races in
      Tunisia is in agreement with the predictions of the chromosomal speciation model
      of White which advocates that karyotypic differentiation between taxa can lead to
      their reproductive isolation and independent evolution. Such a process is
      verified if the Rb process in Tunisia results from local differentiation which is
      supported by both the genetic and morphological data. However, the hypothesis of
      an origin by introduction of these mice from another region of Tunisia or from
      another country cannot be totally dismissed. In this study, an allozymic analysis
      of mice (22Rb and 40Std) from the geographically distant city of Kairouan was
      performed. Results showed that 22Rb and 40Std mice from Kairouan shared the same
      high degree of variability, and were not genetically differentiated. This
      contrasts with the results registered in the two chromosomal races in the Sahel
      towns. Such data argue in favor of a local differentiation of the Robertsonian
      process in Tunisia and suggest that the decrease in variability of the structural
      nuclear genes in the Sahel 22Rb populations can be related to an introduction
      from Kairouan into a Sahel locality resulting in a founder effect or followed by
      a severe bottleneck prior to its dispersion throughout the Sahel region.

PMID- 14658238
TI  - [Incidence and seroprevalence of canine ehrlichiosis in the Medjez El Bab region
      (northwestern Tunisia during 1994, 1995 and 1996].
AB  - A sero-epidemiological survey, realized in the Medjez El Bab region (North-West
      of Tunisia), has concerned 180 dogs which status has been determined during the
      study. The animals were identified, then underwent an annual blood sampling
      during three successive years, in order to search for antibodies against E. canis
      and E. chaffeensis by indirect immunofluorescence. The results show that, in all
      sero-positive dogs, the levels of antibodies against E. canis were higher than
      those against E. chaffeensis. The sero-prevalence of E. canis was 42.8%, 50% and
      48.9%, in 1994, 1995 and 1996, respectively, and was higher than that against E.
      chaffeensis during the three year studies. The incidence of E. canis infection
      was 12.6% during the three years whereas E. chaffeensis infection did not exceed
      4.7%.

PMID- 14658239
TI  - [Surveillance system of maternal mortality in the Tunis region].
AB  - In the framework of a national strategy of reduction of the maternal mortality
      rate. Tunisia has set up a follow up system of maternal deaths occurring in
      public facilities to analyse their causes, the levels of deficiency and to
      propose solutions for preventing them. This note aims at describing the system,
      its results, its efficiency and its limitations in the Tunis region for the years
      1999 and 2000. The results show a maternal mortality rate estimated at 80 for
      100,000 births in public facilities of the region: the main causes being
      haemorrhage (42.1%) followed by infection (13.2%). The proportion of avoidable
      deaths is 87%:74% possibly avoidable and 13% certainly avoidable, factors related
      to women behaviour have also contributed to 45% of cases. The system flows are
      however intricated, and related to organization: an underestimation of risk by
      the patient (33%), an inadequate watch during the postpartum period (25%), a late
      hospitalisation (22%) and not enough reanimation equipment. Nevertheless, this
      control system has achieved part of its objective by starting up a quality
      approach to obstetrical cares and by warning health professionals such as
      obstetricians, anaesthetists, blood banks in charge, hospital managers and other
      medical teams. The limitations of the system are tied to the follow up of the
      real implementation of recommendations stated in reports at a local as well as
      central levels.

PMID- 14658240
TI  - [Epidemiology and prevention of smoking in Tunisia: current situation and
      perspectives].
AB  - This paper describes the trends in tobacco sales and smoking prevalence in the
      Tunisian population, estimates the consequences of smoking on mortality of this
      population, and discusses anti-tobacco actions: educational actions, legislative
      measures and price increases. Sales Data were collected from the Tunisia tobacco
      company. Smoking prevalence data from surveys, conducted by several institutes,
      and numbers of deaths by causes have been estimated from WHO for the year 1998.
      Tobacco sales increased from 4.96 g per adult per day in 1981, to 6.3 g, in 1993,
      then decreased widely. The proportion of smokers was 30% in 1996. 55% among men
      versus 5.6% among women. Among 17 to 24 years old young adults, the proportion of
      smokers was 29.2% in 1994 (50% among men versus 3.9%, among women). Mortality
      attributable to tobacco in Tunisia has been estimated to 6430 deaths in 1997
      (5580 among men versus 850 among women). These deaths represent 22% of the total
      male deaths and 4% of the female ones. Anti-tobacco measures have been reinforced
      by the enactment of anti-tobacco law. Proportion of young smokers remaining
      elevated, it is expected that consequences of the tobacco addiction in Tunisia,
      in term of mortality, will be even heavier in the next two decades, if efficient
      anti-tobacco actions are not implemented.

PMID- 14658241
TI  - [Epizootic equine influenza in Tunisia].
AB  - The authors describe an equine influenza epizootic that occurred in Tunisia
      during February and March 1998 in the regions of Tozeur, Sousse and Tunis. They
      relate the symptoms, the different stages of diagnosis and the serological
      results.

PMID- 14658242
TI  - Mechanical energy flow in the recovery leg of elite race walkers.
AB  - The purpose of this study was to investigate the mechanical energy flow in the
      recovery leg and its relationship to performance descriptors of elite male race
      walkers in an official race. Male race walkers participating in official 20 km
      races were videotaped with a VTR camera (60 Hz) set perpendicular to the course.
      The 28 elite race walkers (race records 1:19'50"-1:33'58") were selected as
      subjects. A two dimensional 14-segment linked model was used to calculate
      biomechanical parameters from the walking motion in the early phase of the race.
      The walking speed was significantly related to the step length but not related to
      the step frequency. Large mechanical energy flows at the hip occurred from the
      trunk to the foot during the first half of the recovery phase and from the foot
      to the trunk during the second half by the joint force power. Joint force powers
      at the hip in the second half of the recovery phase were significantly related to
      the walking speed and the step length. It is suggested that large joint force
      power at the hip would be one of the important factors to obtain high walking
      speed.

PMID- 14658243
TI  - Release parameters at the foul line and the official result in javelin throwing.
AB  - Range in javelin throwing is determined by the release parameters and aerodynamic
      factors. The current study was designed to investigate the effects of release
      speed, release angle and uncorrected angle of attack measured at the foul line on
      the official javelin throwing result. The data were collected in international
      competitions for 26 elite male and 15 elite female javelin throwers (total 248
      throws). Multiple regression models were constructed to predict the range of
      throw for a) individual throwers, b) a group of throwers using the mean value for
      each thrower in the analysis, and c) all individual throws registered for each
      gender separately. The data collection was carried out using a computerised
      photocell gate that consists of two invisible infrared walls two metres apart,
      perpendicular to the throwing direction. Release speed was found to have the
      highest correlation with the official throwing result. The three release
      parameters accounted for 56% of the variance in the official result for the male
      and 51% for the female throwers. For individual male and female throwers, the
      variance explained by the model was between 46 and 87%. Among the individual male
      throwers an increase of 1 m.s-1 in the release speed from 29 to 30 m.s-1 was
      calculated to increase the official result between 2.12 to 6.14 m while among the
      female throwers the effect of increase from 24 to 25 m.s-1 in the release speed
      was from 2.25 to 3.68 m. The study emphasises the importance of investigating
      javelin throwing biomechanics on an individual thrower basis.

PMID- 14658244
TI  - The effect of cycling on muscle activation in the running leg of an Olympic
      distance triathlon.
AB  - The aim of this study was to determine the effect of prior cycling on EMG
      activity of selected lower leg muscles during running. Ten elite level
      triathletes underwent two testing sessions at race pace: a 40 km cycle followed
      by a 2 km run (CR) and a 10 km run followed by a 2 km run (RR). EMG data from
      selected lower limb muscles were collected at three sections of each run (0 km, 1
      km and 2 km) for six strides using a portable data logger. Significant
      differences (p < 0.05) between condition were found for the level of activation
      (Lact) for biceps femoris (BF) during stance and vastus lateralis (VL) during
      flight and stance. Vastus medialis (VM) changed in Lact, during flight, between
      sections in the 2 km run. Furthermore, significant differences (p < 0.05) between
      condition were found for BF during stance and for rectus femoris (RF) and VM
      during flight. There was a significant difference (p < 0.05) in the duration of
      VL activation (Dact) across sections of the 2 km run. Findings from this
      investigation highlight changes in muscle function when changing from cycling to
      running and indicate a need to train specifically for the cycle to run
      transition. Such training may improve performance and reduce the risk of injury.

PMID- 14658245
TI  - Kinematics used by world class tennis players to produce high-velocity serves.
AB  - The purpose of this study was to quantify ranges and speeds of movement, from
      shoulder external rotation to ball impact, in the tennis service actions of world
      class players. Two electronically synchronised 200 Hz video cameras were used to
      record 20 tennis players during singles competition at the Sydney 2000 Olympic
      games. Three-dimensional motion of 20 landmarks on each player and racquet were
      manually digitized. Based upon the mean values for this group, the elbow flexed
      to 104 degrees and the upper arm rotated into 172 degrees of shoulder external
      rotation as the front knee extended. From this cocked position, there was a rapid
      sequence of segment rotations. The order of maximum angular velocities was trunk
      tilt (280 degrees/s), upper torso rotation (870 degrees/s), pelvis rotation (440
      degrees/s), elbow extension (1510 degrees/s), wrist flexion (1950 degrees/s), and
      shoulder internal rotation. Shoulder internal rotation was greater for males
      (2420 degrees/s) than females (1370 degrees/s), which may be related to the
      faster ball velocity produced by the males (50.8 m/s) than the females (41.5
      m/s). Although both genders produced segment rotations in the same order, maximum
      upper torso velocity occurred earlier for females (0.075 s before impact) than
      for males (0.058 s). At impact, the trunk was tilted 48 degrees above horizontal,
      the arm was abducted 101 degrees and the elbow, wrist, and lead knee were
      slightly flexed. Male and female players should be trained to develop the
      kinematics measured in this study in order to produce effective high-velocity
      serves.

PMID- 14658246
TI  - The effect of a flexed elbow on bowling speed in cricket.
AB  - The laws of bowling in cricket state 'a ball is fairly delivered in respect of
      the arm if, once the bowler's arm has reached the level of the shoulder in the
      delivery swing, the elbow joint is not straightened partially or completely from
      that point until the ball has left the hand'. Recently two prominent bowlers,
      under suspicion for transgressing this law, suggested that they are not
      'throwing' but due to an elbow deformity are forced to bowl with a bent bowling
      arm. This study examined whether such bowlers can produce an additional
      contribution to wrist/ball release speed by internal rotation of the upper arm.
      The kinematics of a bowling arm were calculated using a simple two-link model
      (upper arm and forearm). Using reported internal rotation speeds of the upper arm
      from baseball and waterpolo, and bowling arm kinematics from cricket, the change
      in wrist speed was calculated as a function of effective arm length, and wrist
      distance from the internal rotation axis. A significant increase in wrist speed
      was noted. This suggests that bowlers who can maintain a fixed elbow flexion
      during delivery can produce distinctly greater wrist/ball speeds by using upper
      arm internal rotation.

PMID- 14658247
TI  - Technique and timing in women's backward two and one half somersault tuck (205C)
      and the men's backward two and one half somersault pike (205B) 3m springboard
      dives.
AB  - The purpose of this study was to compare the backward two and one half somersault
      dive in a tuck position (205C) performed by females (n = 22) and the backward two
      and one half somersault dive in a pike position (205B) performed by males (n =
      27) and by females (n = 6) to determine changes required by females to
      successfully perform 205B. Video data of the dives performed at the 1999 FINA
      World Diving Cup were captured and digitised to obtain times and postures of the
      divers at specific events including maximum depression, takeoff, and entry.
      Estimates of mass-normalised work done on the springboard were obtained from
      flight times. Males performed 31% more mass-normalised work on the springboard to
      gain height than females. Based on the dive scores and the short time to extend
      and prepare for entry it was concluded that females are not yet able to perform
      205B with the same quality as they perform 205C. Females performing backward
      dives need to adjust their techniques to allow increased work on the springboard
      to generate height and rotation. Also, faster contraction of the hip flexors may
      allow them to achieve the tightest position more quickly to complete rotations
      with more time to prepare for entry.

PMID- 14658248
TI  - The double back salto dismount from the parallel bars.
AB  - The purpose of this study was to identify those mechanical determinants or their
      trends that distinguished a gymnast's best performance of the double back salto
      dismount on parallel bars from those judged to be inferior. Dismounts, in the
      tucked position, by nine Canadian gymnasts were analysed. Unique to this study
      was the inclusive analysis of multiple performances of the same skill by these
      athletes. It was felt that within-subject comparisons would reveal the kinematic
      variables on which the gymnast may focus in order to achieve their best
      performances. A non-parametric median sign test was used to compare mechanical
      variables, within subjects, between the dismount judged the best and those
      dismounts awarded a lower score. Three judges judged each dismount. In comparison
      to poorer performances of the dismount, statistical analyses revealed that
      athlete's best performances were characterised by (1) a higher release point,
      more vertical velocity yet with less angular momentum at take-off, (2) greater
      height, with a tighter and earlier tuck position during the flight phase, and (3)
      a greater range of motion and a more compact squat position at landing (all p's <
      .06).

PMID- 14658249
TI  - Cadence and exercise: physiological and biomechanical determinants of optimal
      cadences--practical applications.
AB  - This critical review reflects the current state of cadence research during
      cyclical activities at different intensities. Moreover, this review aims at
      making suggestions in the areas of evaluation, therapy and sporting performance
      in the light of all the different results reported in studies. A large number of
      researchers have tried to determine the 'optimal' cadence from imposed, preferred
      or spontaneously chosen cadences in order to improve efficiency and performances.
      Results are sometimes conflicting and difficult to explain or interpret. The
      authors have studied the variations in cadences using a reduced number of
      parameters, without links between energetic (oxygen consumption, ventilation),
      biomechanical (force, electromyography) and/or perceived parameters (rating of
      perceived exertion). Conclusions point out that the 'optimal' cadence cannot be
      unique and must be associated with the objectives and individual characteristics
      of the subject (skills and training level, anthropometric parameters). In the
      area of training and reconditioning, cadences would have to be set in relation to
      the nature of cyclical activities and the subjects' condition.

PMID- 14658250
TI  - Young weightlifters' performance across time.
AB  - Prestigious professional organisations have questioned the efficacy of resistive
      training by children or have often neglected to address weightlifting in their
      position papers on resistive training for children. The purpose of this paper was
      to address the deficit in data regarding the efficacy of training children for
      weightlifting and to report data regarding to safety in this population. Eleven
      subjects (3 female, 8 male) who had trained at the USA Weightlifting Development
      Centre in Shreveport Louisiana for a minimum of 22 months (mean = 28.8; SD +/-
      4.4) served as subjects for this study. Means for the pool of subjects subjected
      to t-test to compare data obtained at each subject's initial competition with
      that obtained at the individual's most recent competition revealed significant
      positive changes in body weight, snatch weight, clean and jerk weight, and total
      weight lifted. The latter three were significant both in absolute weight and in
      weight lifted per kg of body weight. Total weight lifted at competitions plotted
      separately for boys and for girls across time indicated an apparently steeper
      slope of improvement for boys. The latter were not tested for significance
      because of the small sample sizes. The lack of injury in training and in 534
      competitive lifts was discussed. None required medical attention or loss of
      training time. It was concluded that there can be no doubt regarding the efficacy
      of weightlifting as carried out at the USA Weightlifting Development Centre. The
      importance of proper application of scientific theory of conditioning in a
      conservative manner for this population was emphasised.

PMID- 14658251
TI  - [Endoscopic surgery of brain structures outside of the cerebrospinal fluid
      space].
AB  - The technique of endoscopy in present-day neurosurgery has been extended also
      outside the liquor space of the brain, especially in the treatment of brain
      bleeding, brain tumors or after brain injuries. The authors describe their
      experience after operating on 45 patients, where the endoscopic intervention has
      been successfully applied therapeutically or at least in preparing a final
      solution by means of microsurgery of radiosurgery. Its has become obvious that,
      in addition to the programmed navigation of the endoscope to the goal, a more
      flexible manipulation with endoscope while using present stereotactic devices.

PMID- 14658252
TI  - [Surgical approach to the sphenoid sinus in microsurgery of hypophyseal tumors].
AB  - Currently there are three major surgical approaches into the sphenoid sinus
      during transsphenoidal microsurgery. The first approach is the sublabial incision
      with submucous resection along the nasal septum. It is particularly advantageous
      in patients with small nasal apertures, in pediatric patients, and for large
      tumors extending into the cavernous sinuses or into the clivus. The second
      approach, the transnasal submucous tunnel, is presently the most frequent
      technique used, although it provides the narrowest operation field. The third
      technique is the direct transnasal approach. This method is less destructive to
      structures in the nasal cavity and less time-consuming. In the period of 20
      months the authors performed 81 transsphenoidal microsurgical operations in 44
      women and 37 men. Visual field defect was the most frequent indication for
      surgery in 42 cases, followed by hormonal abnormality in 24 patients. The
      sublabial approach was used in 69 cases, the technique of transnasal submucous
      tunnel in 10 patients, and the direct transnasal approach in 2 cases. The authors
      encountered no short-term or long-term complications related to various surgical
      approaches to the sphenoid sinus.

PMID- 14658253
TI  - [Anatomic variations in the brachial plexus trunks and nerve roots].
AB  - BACKGROUND: Deviations observed during operations triggered our effort to
      initiate an investigation concerning variations in the formation of brachial
      plexus. MATERIAL AND METHODS: In 50 cadavers of adult subjects the authors
      examined 100 brachial plexuses in order to detect incidence of neural variations.
      The participation of the C4 radix or Th2 radix as well as various variants from
      outlets of individual radices and their branches from the vertebral column to the
      variants in the formation of nerve trunks was investigated. The attention was
      devoted to their course, anastomoses, thickness and occasional absence. In
      addition to anatomical complexity and variability, attention is paid to motor
      innervation peculiarities in relation to diagnosis. The attention is paid to the
      mechanisms and morphological reasons in the origin of certain type of injuries.
      RESULTS: The prefixed type occurred in 24 cases (48%), the postfixed one in a
      singe case. In 25 cases (50%) 32 deviations were observed. The deviations were
      more frequent on the left side in 11 cases. CONCLUSION: The study made it
      possible to find out and describe exceptional, so far unpublished, anatomical
      deviations in the formation of nerve radices and trunks of brachial plexus.

PMID- 14658254
TI  - [Interstitial microdialysis study of changes in metabolism and blood flow in
      skeletal muscles during cardiac surgery with normothermic and hypothermic
      extracorporeal circulation].
AB  - AIM: Hypoperfusion of peripheral tissues and splanchnic organs during cardiac
      surgery in extracorporeal circulation may lead to the origin of serious
      complications. The aim of the study was to monitor metabolism and blood pressure
      in interstital peripheral tissue, skeletal muscle, during the operation on the
      patient with extracorporeal circulation (ECC) in an early post-operation period
      by means of microdialysis. METHODS: The interstitial microdialysis is a minimally
      invasive method for the biochemical monitoring of metabolic changes and blood
      pressure in extracellular space of tissue. The substances in interstitium pass
      across a semipermeable membrane of the inserted microdialysis probe and may be
      analyzed. Microdialysis in this study was performed by means of two microdialysis
      probes CMA (CMA Microdialysis AB, Sweden) inserted into the deltoid muscle of the
      surgically treated patient. The probes were perfused by the Ringer solution at
      the rate of 0.3 ml/hour. The dialysates were sampled in the following intervals:
      beginning of the operation, beginning of ECC, end of ECC, end of the operation,
      two hours during the post-operation period. Standard biochemical methods were to
      evaluate, in the dialysates, glucose, urea, glycerol and lactate. The blood flow
      in the interstitium was monitored by means of dynamic microdialysis of
      gentamycine as a marker. Microdialysis was performed in 40 patients with ischemic
      heart disease, operated on in the extracorporeal circulation. In 20 patients the
      ECC was performed in normothermia (NT), while in the other 20 patients it was
      made in hypothermia (HT). RESULTS: In both groups, NT versus HT, a similar
      dynamism of interstitial concentration of the observed substances in relation to
      the operation phase and in early post-operation period. Low initial
      concentrations were gradually increasing during the extracorporeal circulation
      and increased further after the end of extracorporeal circulation and also in the
      subsequent phase of the operation. The concentration values of the analytes under
      observation were higher in the groups operated on under normothermia, apparently
      due to normal cellular activity during normothermia (versus values in
      hypothermia). Immediately after the operation the observed values decreased in
      the both groups and subsequently gradually increased in the post-operation period
      in the both groups. The trend of dynamic changes of the observed analytes,
      selected as compounds indicating metabolic activity of skeletal muscles during
      hypothermia documents a lower metabolic activity of the cells during hypothermia
      and its marked increase (against NT) in the phase of subsequent normalization of
      the tissue temperature. Analysis of the concentrations of lactate, as a compounds
      mapping anaerobic metabolism of skeletal muscle, revealed similar dynamic changes
      in the both groups (NT vs. HT). There were no significant differences, related to
      the phase of the operation or the phase of immediate post-operation course when
      the both groups were compared. The analysis of gentamycine concentrations as a
      flow marker revealed lower gentamycine concentrations in dialysate during the
      operation, ECC and the early post-operation course in the group operated on in
      normotheramia (vs. HT), indicating a higher tissue flow in skeletal muscle
      against the group of patients operated on under hypothermia. CONCLUSION: The
      results of the microdialysis study demonstrated dynamic changes in interstitial
      concentrations of the observed compounds (glucose, urea, glycerol and lactate)
      related to the phase of operation on the heart in extracorporeal circulation and
      in early post-operation period. A higher perfusion of skeletal muscle was
      documented in patients operated on under normothermia. It became obvious that the
      dynamism in the changes of the compounds observed in the interstitium of skeletal
      muscle was determined by metabolic activity of the tissue as well as by blood
      flow in the muscle interstitium.

PMID- 14658255
TI  - [Emergency surgical myocardial revascularization by means of a temporary arterial
      angioplasty].
AB  - The authors describe the case of a patient who was admitted for four-hour lasting
      acute myocardial infarction of the anterior wall with elevations of ST segments
      on ECG. The finding obtained in selective coronarography revealed an unsuitable
      condition for coronary intervention (a narrow stenosis of the stem, RIA
      occlusion, further two narrow stenoses in the coronary vascular bed). Since an
      operation room was not available at the moment the patient was indicated for
      palliative PTCA RIA (prevention of necrosis evolution) and subsequent urgent
      complete surgical revascularization of myocardium. The uncomplicated post
      operation course and returned function of the affected myocardium indicates that
      the intervention may be considered as a suitable alternative for the treatment of
      acute myocardial infarction.

PMID- 14658256
TI  - [Pharmacologic prevention of SIRS (systemic inflammatory response syndrome) in
      severe thoracic injuries].
AB  - INTRODUCTION: Frequency and severity of the blunt chest injuries are increasing.
      Rather high letality is caused by the injury and following systemic inflammatory
      response. OBJECTIVE: The aim of the study is to verify the efficacy of
      pharmacological blockade of the systemic inflammatory response syndrome (SIRS) in
      serious blunt chest injuries. The aim is also to find out if the administration
      of indomethacin as a cyclooxygenase inhibitor could prevent multiorgan
      dysfunction (MODS) and multiorgan failure (MOF). MATERIAL AND METHODS: Patients
      were divided into 4 groups according to trauma severity (Injury Severity Score).
      The group I. contains patients with ISS up to 17. There is no premise of the SIRS
      development. In the group II. there were patients with ISS 18-30, which means
      polytrauma group due to new definition. In the group III. there were patients
      with ISS 31-40 (severe trauma). Group IV. contains critically injured patients
      (ISS 41 and higher). Some patients involved in our study were given indomethacin
      (as cyclooxygenase inhibitor in arachidonic acid cycle) together with standard
      therapy. RESULTS: 65 patients were included into study in last 14 months, 22
      patients were given indomethacin. The group with indomethacin administration has
      later increase of inflammatory markers in groups III. and IV. This increase also
      takes less time in groups II. and III. Shorter time of mechanical ventilation
      support in group III. in patients with indomethacin was significant. SIRS is
      present in time of admission approximately in 44%. All patients have low
      antioxidants level. 5 patients died in our group, letality was 7.7%. All the died
      patients came from the subgroup without indomethacin, however only one death
      caused by MOF. CONCLUSION: From the results of the first 14 months of the study
      we can conclude that certain number of patients with serious blunt thoracic
      trauma could benefit from indomethacin administration.

PMID- 14658257
TI  - [Hemodynamic basis for the development of varicose ulcers and their therapy].
AB  - The prevalence of leg ulcers is about 1%, approximately 75% of them are of venous
      origin. The precondition for the development of venous ulcers is ambulatory
      venous hypertension. It is assumed than a linear correlation exists between the
      severity of ambulatory venous hypertension and the incidence of venous ulcers.
      Venous ulcers caused by superficial vein reflux are called varicose ulcers and
      are more frequent than postthrombotic ones. Crossectomy removes the hemodynamic
      disorder responsible for the development of varicose ulcers and creates
      conditions for a quick and mostly definitive ulcer healing. In cases with
      simultaneous reflux in the saphenous and femoral veins the saphenous reflux is
      responsible for the severity of venous disorder, whereas femoral reflux is
      hemodynamically unimportant. Selective abolition of saphenous reflux restores
      normal hemodynamic conditions in such cases. Compressive therapy continues to be
      the most frequently used therapeutic procedure in the treatment of venous ulcers;
      it must be considered as a symptomatic measure, because it is not able to
      substantially affect the underlying venous disorder in spite of the fact that the
      correctly lying bandage positively influences venous hemodynamics. The diagnostic
      procedure in patients with leg ulcers should screen out cases with varicose
      ulcers; abolition of superficial vein reflux can deliver these patients from
      their annoying disease.

PMID- 14658258
TI  - [Sentinel node biopsy in colorectal carcinoma--pilot study].
AB  - BACKGROUND: Sentinel lymph node biopsy is a widely accepted method for staging
      melanoma and breast cancer in indicated cases. However, the use of the method in
      colorectal cancer is under clinical investigation. The aim of the pilot study was
      to introduce the technique into the surgical practice in colon carcinoma, to
      determine the feasibility and potential problems and to evaluate the first
      experience. METHODS: Twenty patients with colon cancer underwent lymphatic
      mapping and sentinel node biopsy using blue dye, fluorescein or
      lymphoscintigraphy followed by standard surgical resection. The acquired sentinel
      nodes were investigated with both standard hematoxylin-eosin staining and
      immunohistochemical staining for cytokeratin. RESULTS: Lymphatic mapping
      adequately identified at least one sentinel node (SN) intraoperatively or by a
      modified ex vivo technique in 20 patients (100%). The average number of SN was
      1.5 (range 1-3), non-SN 13.6 (range 1-38) per patient. SN correctly predicted the
      regional lymphatic basin status in 14 cases (70%). The false negative rate was
      40%. No patient has been upstaged on the basis of immunohistochemical staining.
      CONCLUSIONS: Lymphatic mapping and sentinel node biopsy in colon cancer is
      feasible and safe method with a high SN identification rate. The role and
      significance of sentinel node biopsy in colon cancer is not as clear as its role
      in other tumors and remains controversial. Further large prospective studies with
      standardized techniques are needed to evaluate the potential benefit of this new
      method.

PMID- 14658259
TI  - [Crohn disease and laparoscopic surgery].
AB  - AIM OF THE STUDY: To evaluate possibilities of laparoscopic surgery in the
      treatment of Crohn's disease. METHODS: A retrospective evaluation of the group of
      14 patients, operated on in the period of 2/1997 to 2/2003. RESULTS: In the group
      of 7 women and 7 men, laparoscopy was used for ileocecal resection in six cases
      (43%), resection of ileotransversoanastomosis in four cases (29%) and abdominal
      peritoneal amputation of rectum once (7%). The surgical intervention lasted 125
      min on the average. The post-operation complications were not recorded and the
      conversion was not necessary. The post-operation course was complicated by
      suppuration three times in laparotomy (21%) and once by paralytic ileus (7%),
      which required one reoperation. The peristaltics was resumed in the 2nd post
      operation day on the average, when the patients began to refuse analgesics. The
      patients started to accept the liquid diet in the 3rd post-operation day on the
      average and stools appeared on the day 4 after the surgery. The median of post
      operation hospitalization in cases of uncomplicated course was 8 days on the
      average. No patient was lost. CONCLUSIONS: The laparoscopic surgery represents a
      safe alternative in the therapy of Crohn's disease, being associated with a more
      favorable post-operation course and a better cosmetic effect in this group of
      patients with lower age average.

PMID- 14658260
TI  - [Mesenteric venous thrombosis--a shift in therapeutic strategy?].
AB  - The authors present a group of nine patients suffering from mesenteric venous
      thrombosis, which were treated in three hospitals with participation of the first
      author. Basic principles of diagnostic and therapeutic procedure are summarized
      and a shift in the treatment strategy over the last 10 years is pointed out. The
      patient after a very radical intestinal resection may expect to survive and
      entertain an acceptable quality of life, provided the surgery is followed by an
      extensive team care in the post-operation period, later accompanied by the care
      of specialists in modern ways of nutrition.

PMID- 14658261
TI  - [Classic versus laparoscopic appendectomy].
AB  - The authors analyze a cohort of 1,831 appendectomy interventions, performed in
      the years 1996 to 2001 at the Surgery Ward in Prostejov. The laparoscopic
      technique of the intervention was introduced into the ward practice in 1995. The
      evaluation of patients operated on advanced appendicitis by laparoscopy in 1996
      and those operated on in 2001 with a differential approach it became obvious that
      septic complications were markedly reduced when a differential indication for
      laparoscopic intervention was applied.

PMID- 14658262
TI  - [Efficacy and safety in the use of doxazosin (cardura) in the treatment of
      patients with benign prostatic hypertrophy (bph)].

PMID- 14658263
TI  - [Indications for one-stage and delayed urethrectomy after radical cystectomy in
      patients with invasive cancer of the urinary bladder].
AB  - Our aim was to determine indications for urethrectomy in patients with muscle
      invasive cancer of the urinary bladder (UBC) which is essential for choice of
      urine derivation. A total of 51 patients with invasive UBC at the age of 33-78
      years (mean age 60 years) were treated: 7 patients with pT2bN0M0, 1 patient with
      pT2bN1M0, 18 patients with pT3aN0M0, 3 patients with pT3aN1M0, 14 patients with
      pT3bN0M0, 6 patients with pT4aN0M0, 2 patients with pT4bN0M0. Urethrectomy was
      indicated for men with involvement of the prostatic urethra (stage t4a) and
      urinary bladder cervix, multiple tumors of the bladder, pelvic lymph node
      lesions, detection of tumor cells by instant biopsy in the free urethral edge,
      poor differentiation of the tumor (G3) in combination with one of the above
      factors, emergence of urethrorrhagia late after cystectomy; for women with
      involvement of the bladder cervix and Lieutaud's triangle in combination with
      poor differentiation of the tumor cells (G3). Cystectomy was followed by urine
      derivation of the following type: uretero-ureteroanastomosis with nephrostomy (n
      = 2), ureterocutaneostomy (n = 3), Briker's operation (n = 22),
      ureterosygmoanastomosis with creation of sigmoid reservoir (method Mainz pouch
      II) (n = 21), Studer orthotopic plastic reconstruction (n = 2) and Hautmann
      plastic surgery (n = 1). Urethrectomy was made in 16 patients. One-stage
      operation was conducted in 14 patients (suprapubic approach--8 males, perineal
      one--in 6 females). Delayed urethrectomy was made in 2 patients. Intra- and
      postoperative complications caused by urethral removal were absent. Corrected 2
      year survival for all 51 patients was 70.8 +/- 11.3%. Among the deceased were 2
      patients who had undergone urethrectomy at the stage T2b and T4a 5 and 8 months
      after primary operation, respectively. Thus, we believe that urethrectomy must be
      made in the above indications and poor differentiation of the tumor cells (G3).

PMID- 14658264
TI  - [Comparative assessment of the WHO and Gilson histological classifications of
      prostatic neoplasms (taking into account data of ploidy studies)].
AB  - We estimated ploidometric nuclear parameters of predominating cell population in
      various prostatic adenocarcinomas in using WHO vs Glison classification to define
      advantages of the above classifications. Ploidometry provides information on cell
      composition and proliferative activity of cells. We observed greater ploidity in
      different grades of cell atypia. WHO histological classification by
      differentiation grade corresponds to ploidometric characterization of tumor cell
      populations but fails to reflect the presence of different histological types of
      the tumor. Currently introduced classification by Glison is more effective both
      diagnostically and prognostically as it reveals a dominant histological type of
      the tumor and shows other variants of tumor growth progression.

PMID- 14658265
TI  - [A multicentric variant of renal carcinoma growth].
AB  - 78 kidneys removed for cancer in 1999-2002 were studied for multifocal growth of
      the tumor. The results demonstrated a direct correlation between multicenter
      growth of renal cell carcinoma (RCC), size of the primary tumor and stage of the
      disease. Most of the additional foci were detected at the distance of more than
      2.0 cm from the primary tumor, i.e. outside the safety zones in conduction of
      organ-saving operations. Frequent coincidence of a morphological type of the
      primary and additional tumors (70%), degree of cell differentiation (80%) and
      higher incidence of multifocality in infiltrative growth of the primary tumor
      support the existing hypophysis about the role of intra-organ metastasizing as
      the underlying cause of multifocal lesions. Also, the study confirmed low
      preoperative detection of multifocality: 1.8% preoperatively and 19.2% under
      investigation.

PMID- 14658266
TI  - [Dorsal graft urethroplasty techniques].

PMID- 14658267
TI  - [Transrectal microwave hyperthermia in the treatment of chronic prostatitis].
AB  - The efficacy of transrectal microwave hyperthermia (TMH) was investigated in 124
      patients aged 20 to 55 years. Of them, 75 (60.5%) patients had chronic
      noninfectious and 49 (39.5%) patients infectious prostatitis. In addition to
      standard pre- and posttreatment examinations the following tests were made:
      bacteriological and biochemical tests of prostatic secretion, uroflowmetry,
      transrectal color Dopplerographic mapping. The course of the treatment included
      10 one-hour sessions of microwave hyperthermia, drug therapy and prostatic
      massage. Patients with both forms of chronic prostatitis exhibited disorders of
      prostatic circulation, activated lipid peroxidation, low concentration of
      catalase in the organ secretion, defective urodynamics of the lower urinary
      tracts. More pronounced changes occurred in noninfectious process. Microwave
      hyperthermia produced clinical improvement, recovery of hemodynamics in the
      prostate, structure and function of cell membranes in prostatic secretion,
      positive response of urodynamics. Thus, TMH generated on domestic equipment can
      be considered as one of the methods of pathogenetically sound treatment of
      noninfectious and infectious chronic prostatitis.

PMID- 14658268
TI  - [Psychophysiological characteristics of patients with chronic prostatitis].
AB  - The aim of the study was to characterize mental changes in chronic prostatitis
      (CP) patients after the addition of a combination of local and central reflex
      physiotherapeutic factors to combined treatment 149 patients with infectious and
      noninfectious CP entered the study. The study group (n = 94) received combined
      treatment including physiotherapeutic factors (ANDRO-GIN unit). The control group
      (n = 55) received standard CP therapy. All the patients have undergone clinical,
      laboratory, device and psychophysiological examinations. Thus, addition of
      physiotherapy to combined treatment of CP raises the treatment efficacy and
      promotes optimization of "an internal picture of illness"--one of major
      characteristics of the patient's psychological condition.

PMID- 14658269
TI  - [Features of mental disorders in patients with chronic pyelonephritis].
AB  - To study prevalence of mental disorders in patients with chronic pyelonephritis
      (CP), 50 CP patients were examined clinically and with special tests (fundus of
      the eye, EEG. AMPI, Luscher's test). The patients were diagnosed to have a wide
      spectrum of mental disorders: psycho-organicsyndrome, paroxysmal disorders,
      hallucinations, obsessions depression, asthenic syndrome. The presence of
      psychoorganic syndrome, paroxysms, hallucinations point to developing organic
      disorders of the brain the severity of which correlates with the age. The
      depressions had a complicated genesis (psychogenic, somatogenic and organic). The
      results of the study can be used for design of therapeutic and rehabilitative
      measures improving quality of CP patients' life.

PMID- 14658270
TI  - [Diagnosis and treatment of vascular erectile dysfunction with the vibration
      vacuum penis stimulator "Sanos"].
AB  - The paper describes a new device for treatment of vascular erectile dysfunction-
      the vibrovacuum fallostimulator "Sanos". This method differs from conventional
      local decompression in a dynamic regimen of vacuum effect on the penis in the
      presence of vibration. The resultant reduced exposure of the organ to vacuum
      prevents such serious complications as edema, hemorrhages and necrosis of penile
      skin. The dynamic vacuum regimen is also effective in restoring erectile activity
      of the penis producing erection similar to physiological. A 10-15-day course of
      vibrovacuum fallostimulation was conducted in 330 patients with vascular erectile
      dysfunction. Recovery of arteriocavernous blood flow was registered in 92.1%. No
      complications occurred. The above method can be also applied for diagnosis of
      both insufficient arterial circulation in the penis and defects in venoocclusive
      mechanism of erection.

PMID- 14658271
TI  - [Emoxipin in combined pharmacological defense of the kidney from ischemia and
      operative stress (an experimental study)].
AB  - The paper presents experimental results of the study of kidney defense from
      normothermic ischemia and operative stress in interventions with stopping renal
      circulation. The antiischemic effect of emoxipin was studied in monotherapy and
      in combination with furosemide and verapamil. The above effect was found
      positive, especially in response to combined use of emoxipin, furosemide and
      verapamil.

PMID- 14658272
TI  - [Contact ureterolithotripsy by the Ho laser "Medialis H" by the firm "Dornier"].
AB  - The authors describe results of application of Ho laser "Medilas H" (Dornier) in
      patients with uroliths located in different parts of upper urinary tracts. The
      results of new approaches to uroliths fragmentation in different parts of the
      ureter are outlined.

PMID- 14658273
TI  - [Diagnosis and treatment of recurrent surface cancer of the urinary bladder
      (early repeated cystoscopy and biopsy)].
AB  - In spite of some achievements in the field of oncourology, the problem of
      diagnosis and treatment of surface cancer of the urinary bladder (SCUB) remains
      urgent because of early recurrence and progression after TUR (50 and 30%,
      respectively). Repeated cystoscopy and biopsy early after surgery enable the
      physician to establish a real stage of SCUB (invasion into the bladder wall-
      criterion T and cell differentiation--criterion G). Early accurate staging of the
      disease allows design further policy of treatment. Early repeated cystoscopy and
      biopsy detected recurrence of transient cell SCUB in 51 (24.75%) patients. In 20
      (9.7%) patients recurrent tumor located at the site of the previous operation. In
      other places recurrences were detected in 31 (15.05%) patients. Recurrent tumor
      was found in 23 (11.16%) cases at stage Ta and 28 (13.6%) patients at stage T1;
      in 15, 30 and 6 patients with high, moderate and low malignancy grade (22.06,
      24.79 and 35.29%, respectively). SCUB progression developed in a total of 15
      (7.28%) patients: by T criterion (T1-T2a) in 9 (4.37%) patients and by criterion
      G (G2-G3) in 6 (2.91%) patients. Thus, early repeated cystoscopy and biopsy
      detect early residual and recurrent SCUB facilitating design of further treatment
      policy.

PMID- 14658274
TI  - [Functional state of the lower urinary tract in children with enuresis].
AB  - Basing on rich statistical materials, the authors studied functional state of the
      lower urinary tracts in children and adolescents with enuresis. A noticeable
      reservoir dysfunction of the bladder was found in the probands while evacuatory
      function did not differ much from healthy controls.

PMID- 14658275
TI  - [Leiomyoma of the urinary bladder].

PMID- 14658277
TI  - [Evaluation of efficacy of lithotripsy in reno-ureter lithiasis].

PMID- 14658276
TI  - [Cytogenetic features of renal carcinoma].

PMID- 14658278
TI  - [Vladimir Ivanovich Shapoval].

PMID- 14658279
TI  - [Bioeffects of chronic exposure to radiofrequency electromagnetic fields of low
      intensity (standardization strategy)].
AB  - A retrospective analysis of the experimental researches on the effect of radio
      frequency electromagnetic fields (EMF) on human health, carried out in the USSR,
      is presented. The results of chronic exposure of laboratory animals to EMF have
      been considered. Apparently, EMF in the range of 1750-2750 MHz with power density
      up to 100-500 W/cm2 caused in immune globullin fractions, and a development of
      autoimmune processes. The changes in parameters of reproductive functions and
      posterity, the increase in embryo mortality were found. The standartization
      strategy used in the USSR and currently applied in Russia has been discussed.

PMID- 14658280
TI  - Basic problems of diversely reported biological effects of radio frequency
      fields.
AB  - The large differences in RF safety standards are due to different philosophical
      approaches to public health standards development, different scientific
      approaches and interpretations of the scientific data, and different
      jurisdictions in various countries. In this paper, the origin of these
      differences is explored. The emphases are on the basic problems of why reported
      biological effects of RF fields are controversial, and how the general public can
      be misinformed. While there are differences in approaches and methods, science
      should converge and not diverge in finding the threshold level for exposure to
      EMF that is not adverse to human health. As the progress in technology continues
      and human beings are enjoying an increased quality of life, it is essential for
      scientists to ensure that safety is not compromised. More importantly, it is the
      responsibility and moral obligation of scientists and the media to bring
      "verified" information to the public. Scientists must conduct well-designed
      studies and to report the results in a clear and detailed manner, so other
      independent investigators can repeat the study or explore further. Mistakes must
      be minimized and stopped at the first level of scientific research.

PMID- 14658281
TI  - [Importance of initial status of the nervous system in the developing of low
      intensity EMF exposure neuro-effects].
AB  - EMF neuro-effects are weak or under-threshold irritants (from the position of
      biological significance) and completely determined by initial status of nervous
      system. Initial brain bioelectrical activity characterized by the first
      developing symptoms of drowsiness or passive awaking condition promotes the
      reaction development. But emotional tension or somatic activation interfere this
      process. This dependence could be remedied by increasing of biological
      significance of low intensity EMF and changing of the analyzed physiological
      parameter.

PMID- 14658282
TI  - [The efficiency and direction of thymus changes after whole-body exposure of mice
      to the weak electromagnetic field are determined by the initial status of the
      thymus].
AB  - The work presents results of the experimental study on thymus changes developing
      after whole-body exposure of mice to ultralow power pulse-modulated
      electromagnetic field (carrying frequency 2.39 GHz, modulating pulses with
      frequency 4 Hz, duration of impulses 0.025 sec, average power density 60 mW/cm2,
      absorbed dose 0.086 J/g or 0.172 J/g). It was shown that a percent of the
      microwave induced increase or decrease of thymus mass and the number of cells in
      the organ (y) are determined by the initial mass or number of cells in thymus
      accordingly to equation of linear regression: (yx = 215-2.25x, where x is the
      thymus mass of control animals (in a range 31-63 mg) and (yx = 178.6-41x, where x
      is the initial number of cells in thymus (in a range 0.6 x 10(8)-2.6 x 10(8))
      reduced by a factor of 10(8).

PMID- 14658283
TI  - Biological effects of EMF exposure on Ets genes.
AB  - Ets genes are transcription factors expressed in different tissues. Biochemical
      pathways interfering with the intracellular calcium ion concentration are known
      to influence members of this gene family. Considering experimental observations
      and previous reports, we proposed a hypothetical model of interaction between EMF
      and Ets, based on possible interference in pathways involving calcium as a second
      messenger. This approach comprehend different hypothesis and may contribute to
      clarify EMF biological effects, providing an experimental model and a procedure
      based on gene expression analysis. Additional knowledge on biological mechanisms
      is required to support these promising results. Further experiments are in
      progress to assess the role of EMF in modulating gene expression and its
      biological meaning. Identification of early endpoints is needed for mechanism
      understanding and development of sensitive biomarkers for molecular epidemiology
      studies.

PMID- 14658284
TI  - [Activity of natural killer cells of the spleen of mice exposed to low-intensity
      of extremely high frequency electromagnetic radiation].
AB  - The dose dependence of natural killer (NK) cell activity from mouse spleen upon
      action of low-intensity millimeter waves in the exposure range from 5 to 96 hours
      was studied. It has found an increase of NK activity by 24 hours posttreatment
      that returned to normal level in a day after the cessation of the irradiation.
      Also the stimulation of isolated NK cell activity after millimeter waves
      treatment within 1 hour was revealed.

PMID- 14658285
TI  - [Kinetic parameters of androgen receptor complexes and the activities of the
      glycolysis and oxidative pentose phosphate pathway key enzymes in rat testis
      cytosol after whole body 60-min exposure to high frequency electromagnetic field
      (39.5 Ghz)].
AB  - The effect of electromagnetic field of millimeter range on biochemical indices of
      testicles of totally exposed rats at various periods of observation (day 1, 10,
      30, 90) was studied. The following functional shifts were revealed: the 6
      phosphogluconate dehydrogenase activities enforced approximately up to 130% on
      30th day in comparison with the controls, but in three months (90th day) the
      activity returned to normal values: glucose-6-phosphate dehydrogenase an puruvate
      kinase did not show obvious changes of activities. On the contrary, there were
      surprising differences in behavior of androgen-receptor system: the number of
      androgen-receptor sites in cytosol was increased significantly on 1st day after
      exposure (114%); on 10th day concentration of RA was quite oppositely 1.68-fold
      reduced in relation to the control; through 1-month after exposure the rising of
      [RA] (123%) was registered; however, to 3-month term the significant fall (1.42
      times) of the RA contents in testicular cytosol persisted.

PMID- 14658286
TI  - [Study of bioeffects of ship-borne microwave navigation radar in chronic
      experiments].
AB  - The influence of microwaves, generated by navigation radars, on the animals'
      behavior, their antioxidant and reproductive systems were studied. It was found
      that the exposure to power of 1000 (microW/cm2)h exceeded the threshold of
      harmful action of electromagnetic radiation.

PMID- 14658287
TI  - [Biological effects of mobile phone electromagnetic field on chick embryo (risk
      assessment using the mortality rate)].
AB  - Chicken embryos were exposed to EMF from GSM mobile phone during the embryonic
      development (21 days). As a result the embryo mortality rate in the incubation
      period increased to 75% (versus 16% in control group).

PMID- 14658288
TI  - [Anthropogenic EMF effects on the condition and function of natural ecosystems].
AB  - A review of Russian and foreign studies of EMF effects on living environment was
      made. Vast range of EMF frequencies and intensities affect on functions and
      condition of ecosystems. Even non-thermal EMF levels could cause reversible
      changes in physiological process regulation. Some changes were observed in animal
      behavior such as motive activity, spatial orientation, reduction of ability to
      form a conditioned response. Some animal species (some insects, birds, reptiles)
      use electromagnetic fields for spatial orientation during migration. Biological
      communities are very sensitive to EMF effects and could become the biological
      indicators of electromagnetic pollution.

PMID- 14658289
TI  - [The influence of electromagnetic radiation of industrial frequency on Daphnia
      magna (Straus)].
AB  - The influence of electromagnetic radiation of industrial frequency on survival,
      efficiency, physiological parameters of Daphnia magna (Straus) was investigated.
      The electromagnetic field with intensity of a magnetic component 15 microTl and
      an electrical one 12 kV/m was generated. The researches were carried out in acute
      and chronic experiments. The experimental group was exposed to electromagnetic
      radiation for 8 hours daily for 30 days. As a result of the study it was revealed
      that the influence of electromagnetic radiation with the given parameters did not
      have the lethal effect on the test objects. It was found that electromagnetic
      radiation negatively affected Daphnia fertility. On the average, a real fertility
      of the Daphnia in the experimental unit was 26.32% compared to the control. The
      age of puberty in the experiment increased twice in comparison with the control.

PMID- 14658290
TI  - [Remote effects of occupational and non-occupational exposure to electromagnetic
      fields of power-line frequency. Epidemiological studies].
AB  - A retrospective cohort study of mortality in the personnel of power-supply plants
      in the European regions of Russia was carried out. The exposure of the personnel
      to electromagnetic fields of power-line frequency (PF) was taken into account.
      Statistically non-significant raise of mortality from leukemia was found,
      compared to low mortality rates due to all other causes including cancer of any
      type. Standardized mortality ratio (SMR) was equal to 2.03 (95% CI = 0.23-7.31).
      In the retrospective case-control study the haemoblastosis development risk under
      occupational PF EMF exposure was evaluated. The data of 571 "cases" and 1208
      "controls" interview showed that odd ratio (OR) was 1.64 (95% CI = 0.8-3.1). In
      another retrospective case-control study the risk of the haemoblastosis
      development in children due to parents PF EMF occupational exposure was
      evaluated. The data of 208 "cases" and 319 "controls" interview showed that the
      odd ratio (OR) was 1.69 (95% CI = 0.7-3.3). A retrospective cohort study of
      mortality in a settlement situated near a high-voltage (500 kV) substation, which
      took into account PF EMF levels in residential areas, revealed low mortality
      rates, except leukemia mortality (SMR 1.3; 95% CI = 0.2-7.0). The obtained data
      do not allow excluding a possibility of PF EMF leukogenic effect.

PMID- 14658291
TI  - [Epidemiological risk assessment of pathology development in occupational
      exposure to radiofrequency electromagnetic fields].
AB  - A cross-sectional study of working conditions and health of the personnel of the
      civil aircraft radar-tracking system has been conducted based on periodical
      health examinations. The personnel was divided into three occupational groups.
      Group I was exposed to EMF EHF, group II--to EMF HF and UHF and group III was not
      exposed to EMF (reference group). The groups didn't differ in any occupational
      and non-occupational parameters. Health status of 250 workers was examined. High
      prevalence rate of cardiovascular diseases (ICD-X I00-I99) was found in the
      exposed groups. Odds ratio (OR) was 3.78 (95% CI 1.96-7.27) in group I and 2.13
      (95% CI 1.13-4.03) in group II. High prevalence rate of cardiovascular diseases
      is explained by arterial hypertension (ICD-X I10-I15) (OR = 1.96 95% CI 1.04-3.70
      in group I and OR = 1.80 95% CI 0.93-3.50 in group II) and ischemic heart disease
      (ICD-X I20-I25) (OR = 7.9 95% CI 3.48-18.06 in group I; OR = 3.0 95% CI 1.23-7.33
      -in group II). In the exposed groups cardiovascular diseases were developed in
      young age. OR was 7.04 (95% CI 1.64-30.19) in group I and 4.33 (95% CI 0.96
      19.65) in group II in 30-39 age sub groups. Myocardium infarction was found in 2
      out of 16 persons of this age in the group exposed to EMF.

PMID- 14658292
TI  - [The remote effects of chronic exposure to ionizing radiation and electromagnetic
      fields with respect to hygienic standardization].
AB  - A variety and rate of non-cancer diseases occurred in humans as a result of
      chronic exposure to ionizing radiation or to electromagnetic radiation (EMR) of
      high and superhigh frequency have been compared. The intensity of EMR was
      slightly higher than a sanitary standard for population. A risk of health
      impairments in workers having occupational exposure to EMR was assessed on the
      basis of Selie's concept of development of non-specific reaction of the body to
      chronic stress factors (general adaptation syndrome), models of changes in the
      body compensatory reserves and calculations of radiation risk after severe and
      chronic exposure to ionizing radiation.

PMID- 14658293
TI  - [Some aspects of animal-to-human approximation of low frequency electromagnetic
      field exposure conditions].
AB  - Appropriateness of representation of a biological object surface as an
      equipotential surface has been proved for conditions of a quasistatic exposure to
      EMF of frequencies lower than 1 MHz. The conditions, at which a self capacitance
      of a biological object is its basic electrical parameter, have been considered. A
      factor of animal-to-human approximation of low-frequency EMF exposure conditions
      was estimated on the basis of equal dose loading in biological objects of
      different geometric sizes.

PMID- 14658294
TI  - [Some magnetic-biological problems of distant and long-term space flights].
AB  - Some magnetobiological problems of orbital (in the geomagnetic field--GMF) and
      interplanetary (in hypomagnetic conditions) flights are considered. The influence
      of electromagnetic fields (EMF) created by systems and equipment of the space
      vehicle (SV) are touched also. A level of the geomagnetic field (GMF) onboard
      during the orbital flights is discussed. Its periodic variations onboard owing to
      movement of SV on an orbit are analyzed. The reader's attention in attracted to
      the papers by R.M. Baevsky et al. in which the influence of magnetic storms and
      periodic variations of GMS on the cardiovascular system of astronauts onboard are
      shown. Possible ways and mechanisms of the influence are discussed. The wrong
      assertions in a number of works namely that at orbital flights an appreciable
      electrical field is induced in an organism of an astronaut in a space-craft and
      the electrical field may by responsible for some biological impacts are analyzed.
      The situation at the future in the terplanetary flights (for example Martian
      missions) when a crew and biological objects for a long time will be in the
      interplanetary magnetic field (by several orders less then GMF) is considered. As
      applied to the flights the opportunities of generation onboard the "artificial"
      GMF are outlined. The ensuing biological and technical questions are discussed.

PMID- 14658295
TI  - [Assessment of the contribution of broadband quasi-continuous electromagnetic
      background to dose loading].
AB  - Assessment of probable dose loading due to a broadband quasi-continuous
      electromagnetic background is presented. A level of the quasi-continuous
      background in the appropriate frequency intervals could exceed maximum
      permissible exposure by a factor of several tens. For safety monitoring, it is
      suggested to use the equipment that allows registering of EMF amplitude and
      frequency in a wide frequency range, with sensitivity by order of magnitude
      greater than MPE.

PMID- 14658296
TI  - [Effects of perturbed geomagnetic field on connective tissue metabolism and some
      systems of homeostasis after hydroxyapatite implantation].
AB  - The influence of perturbed geomagnetic field (PGMF) on glucocorticoid,
      epinephrine, hydroxyproline content in intact rats and after intramuscular
      implantation of demineralized bone matrix and combined (hydroxyapatite/bone meal)
      samples was investigated. It was found that the exposure of the intact rats to
      PGMF led to decrease in free and peptide-bound hydroxyproline in plasma. In the
      rats with hydroxyapatite/bone meal samples placed in ectopic sites the exposure
      to PGMF normalized hydroxyproline, glucocorticoid and epinephrine content.

PMID- 14658297
TI  - [Effects of electromagnetic field of thermal intensity on the hypophysis-thyroid
      unit of the neuroendocrine system].
AB  - Acute 12-minute exposure of laboratory rats to microwaves with specific dose rate
      (SAR) of 30 W/kg that exceeded a basal metabolism caused a transient response of
      hyppophysis-thyroid system of compensatory-adaptive character. Prolonged exposure
      to microwaves of less intensity (SAR = 6 W/kg, which approximately corresponds to
      basic metabolic rate for these animals) caused insufficiency of the function of
      thyroid control in a form of primary hypothyroidis.

PMID- 14658298
TI  - [Comparative estimation of the effects of continuous and intermittent cyclical
      microwave radiation on the behavior of rats in the extraordinary situation].
AB  - Research has been carried out to investigate the effects of pulsed microwave
      exposure without pause (7 GHz, 400 pps, 100 microseconds, 70-150 mW/cm2, exposure
      10 min) and pulsed interrupted cyclical microwave exposure (5 min exposure--4 min
      pause--5 min exposure) on learned behaviors of rats in the paradigm of
      extraordinary situation (the rescue of the life). It was shown that reductions in
      conditioned behavior after acute pulsed microwave exposure occurred at SAR of 21
      W/kg (100 mW/cm2) and after cyclical pulsed microwave exposure at SAR of 28.4
      W/kg (135 mW/cm2).

PMID- 14658299
TI  - [Neuroimmunoendocrinology: beginning and prospective development].
AB  - The paper gives analytical consideration of what, as to how evolved current
      notions of the new branch of neurobiology, the neuroimmunoendocrinology, dealing
      with integration of the main physiological regulatory systems--netvous, endocrine
      and immune, with special reference paid to the developmental likeness of their
      controlling mechanisms, letting to assume their cooperative action. Taking the
      latter into consideration the opportunity is discussed, suggesting that breakage
      of those would result in various kinds of disregulatory pathology including
      autoimmune one.

PMID- 14658300
TI  - [Memory and potassium channels].
AB  - The K(+)-channels of the surface membrane play a crucial role in the generation
      of electrical activity of a neuron. There is a large diversity of the K(+)
      channels that depends on a great number (over 200) of genes encoding channels
      proteins. An evolutionary conservation of channel's proteins is determined. The
      K(+)-channels were found to have a great importance in the memory processes. It
      was shown on different model systems that K(+)-current of the surface membrane
      decreases during the learning. The antagonists of K(+)-channels were found to
      improve the learning and memory. It was revealed in electrophysiological
      experiments that K(+)-channels antagonists can either themselves induce a long
      term synaptic potentiation or intensify the synaptic potentiation induced by a
      tetanization. The disfunction of K(+)-channels is believed to be an important
      link in the mechanisms of memory disturbances. In animal mutants with K(+)
      channels disfunction, learning and memory are deficient. In behavioral
      experiments, the use of K(+)-channels openers make the learning worse. Amnesia
      caused by cerebral ischemia is explained by strong activity of K(+)-channels
      which not only inhibits neuronal excitement but also causes neurodegeneration.
      The question on the K(+)-channels involvement into pathophysiology of Alzheimer's
      disease is discussed. Neurotoxic peptide beta-amyloid, which is supposed to be
      involved into mechanisms of Alzheimer's disease, modulates K(+)-channels
      function. The effect of beta-amyloid depends on the subtype of K(+)-channels: A
      channels are inhibited, and KDR-channels, on the contrary, become stronger. The
      effect of the cognitive enhancers (vinpocetine, piracetam, tacrine, linopirdine)
      on K(+)-current also depends on the subtype of K(+)-channels. Slow-inactivating
      K(+)-currents (IDR, IK(Ca), IM) are inhibited in the presence of these drugs,
      while fast-in-activating K(+)-current (A-current) remains unchanged or even
      increases.

PMID- 14658301
TI  - [Role of the pineal gland in the body protection from injury].
AB  - Pineal gland phylogenic antiquity, its involvement in the stress reaction and
      many-sided activity of its compounds permit to consider the gland to be the organ
      taking an active part in the body protection against injury, which is essential
      for everyone since its appearance on the planet. The available data prove that
      almost all the reactions developing in the organism from the moment of trauma up
      to the complete wound reparation are under the pineal control. Being always an
      urgent one the problem of traumatism increased nowadays because of pineal
      dysfunction. It makes the premises to apply pineal secret products in traumatic
      disease as a kind of replace therapy that is suggested to be not less successful
      than glucocorticoid administration in shock.

PMID- 14658302
TI  - [Functional organization of a photoperiodic brain system].
AB  - The neurofunctional system, which receives a photoperiod, is a photoperiodic
      brain system. As a part of chronoperiodic system of organism it is involved in
      perception and transfer of information about the main external Zeitgeber to the
      peripheral tissues. Such role of photoperiodic system allows it not only
      synchronize the chronorhythms of different somatic and visceral functions, but
      also realize the coordination and the modulation of adaptation mechanisms to the
      stressors influence. The present review is focused on the ways of conduction of
      photoperiodic information, role of suprachiasmatic nuclei of hypothalamus in
      endogenous oscillation of chronorhythms and pineal gland as a neuroendocrinal
      transducer; and also on characteristics of circadian and circannual parts of
      photoperiodic system. Special attention is given to vegetative part of
      photoperiodic system and melatonin--"the hormone of dark". It is supposed that
      adenosine, one of the humoral elements of photoperiodic system, is involved in
      transfer of duration of the light part of photoperiod. Due to presented data we
      have come to the conclusion that septohippocampal system is one of the center for
      saving photoperiodic information.

PMID- 14658303
TI  - [Mechanism of opioid and substance P-mediated modulation of cortical signal
      transduction through the striatum].
AB  - A mechanism of opioid and substance P-mediated modulation of a cortical signal
      transduction through the striatum is suggested. According to this mechanism, an
      activation of postsynaptic receptors, bound to Gi/0 proteins, should increase the
      magnitude of NMDA-dependent (NMDA-independent) LTD (LTP) of excitatory inputs and
      LTP (LTD) of inhibitory inputs to all types of striatal cells. An activation of
      postsynaptic receptors, bound to Gs or Gq/11 proteins, should oppositely modulate
      LTD and LTD in the same inputs. It follows from the model that the negative
      feedback loops can held the activity of a striatal output cells at the stable
      level due to recurrent activation by endogenous opioids of delta receptors on
      striatopallidal cells, mu and kappa receptors on striatonigral cells of
      striosomes and matrix, respectively, and subsequent suppression of the efficacy
      of corticostriatal inputs. Cholinergic interneurons, affected by enkephalin and
      substance P, are also involved in these feedback loops. We hypothesized that an
      activation of mu and delta receptors and/or inactivation of kappa receptors on
      striatal spiny cells might alleviate parkinsonian symptoms and recover locomotor
      activity.

PMID- 14658304
TI  - [Corticotropin-releasing hormone in the regulation of adaptive behavior].
AB  - Recent findings on the role of corticotropin-releasing hormone (CRH) in the
      regulation of stress and its consequences are summarized and analyzed in the
      review. Being involved in stress-activating system this neurohormone is referred
      to as a neurochemical factor triggering and integrating both endocrine and
      behavioral functions. The CRH distribution in hypothalamus and extrahypothalamic
      brain regions relevant to its involvement in the controlling of endocrine
      processes and behavior is viewed in details. Distinct behavioral outcomes of
      stress and the contribution of amygdalar, hippocampal, and striatal CRH
      structures, implicated in general organism response to external influences, are
      widely discussed. From this viewpoint the mechanisms involved in the development
      of post-stress psychopathology, as well as drug addiction and alcoholism are
      treated.

PMID- 14658305
TI  - [Functional asymmerty of the brain and emotions].
AB  - Different kinds of emotional phenomena are related in a different way with the
      workings of the left and right hemispheres of the brain. Emotional reactions
      (phasic emotions), which appear on the basis of a cognitive loading (mental
      representation, recognition, play, prognostication, watching movies, reading of
      emotionally colored texts or separate words and so on) and which are tested with
      the help of electrophysiological methods, activate different regions of the left
      and right hemispheres of the brain depending on the complexity and novelty of
      emotiogenic situations as well as on the degree of subject's emotional tension.
      The tonic emotions individual background-mood, on which depends the emotional
      estimation (negative of positive) of the presented stimuli or events, are
      determined mostly by a prolonged, relatively stable, tonic activation of each
      hemisphere connected with subjects' individual characteristics. The predominance
      of the left hemisphere activity creates positive emotional background, whereas
      the predominance of the right hemisphere creates negative background.

PMID- 14658306
TI  - [Seasonal dynamics of oviposition in non-autogenous population of Culex pipiens
      pipiens (Diptera: Culicidae) in the Leningrad province].
AB  - Seasonal patterns of oviposition in a synanthropic unautogenous population of
      Culex pipiens pipiens mosquitoes from 69 suburban settlements (60 degrees 30' N,
      30 degrees E') of the Leningrad province were studied during the period 1998-2002
      years. The numbers of egg rafts laid in six artificial pools (barrels) were
      counted every day; altogether 692 rafts were collected. The general patterns of
      oviposition activity were similar for all studied years, in spite of their
      differences in the summer temperature regimes. The first peak of oviposition was
      observed during the second decade of July, the second peak--during the third
      decade of July--the first decade of August. The first and second summer
      generations of mosquitoes were responsible for these oviposition peaks, whereas
      the third generation completely entered the reproductive diapause. Thus, the
      oviposition activity was successfully used for populational monitoring of C. p.
      pipiens, that was for the first time recommended by Madder and co-authors (1980),
      taking into consideration the simplicity and economy of this technique. The
      differences in the attractiveness of distinct reservoirs for oviposition were
      recorded. The females preferred the barrels located on open sun-lit space and
      waters with organic pollution settled by mosquito larvae. Windly and rainy
      weather and also low (below 10 degrees C) night temperatures suppressed mosquito
      oviposition.

PMID- 14658307
TI  - [A burrow of a little ground squirrel as a consortium].
AB  - Structure of consortia as an animal community inhabiting a mammalian burrow with
      an example of the little souslik Spermophilus pygmaeus Pallas from Western
      Kazakhstan was studied. Species composition, numbers and distribution of
      invertebrates in different types of burrows and nests of the little souslik were
      examined on the background to their food dependencies on the host. The consortia
      is considered as a system of concenters around the host of burrow (center of
      community, CC). Recognized concenters are given with ranks based on food
      relations between invertebrate inhabitants and CC: concenter of I rank includes
      direct parasites and predators of CC, II rank is represented by consumers of dead
      bodies of the souslik and its life activity products; III rank includes predators
      and parasites of souslik's cohabitants, and concenter of IV rank encompasses
      animals, which use the burrow as a refuge only. Within limits of each concenter,
      a number of "rondos", groups of animals attributed to certain systematic
      category, for example ticks, gamasid mites, certain insect orders etc., may be
      recognized.

PMID- 14658308
TI  - [Behavioral reactions of the horse flies of the genus Hybomitra (Diptera:
      Tabanidae) during a flight around a host and searching places for bloodsucking].
AB  - Flight trajectories of horse flies Hybomitra attacking a single host (a cow) have
      been registered on record cards by the method of Knipest (1981). The trajectories
      in a search on integuments of preferred places for feeding are described, as well
      as the responses caused by defensive activity of the cow are considered. The role
      of sensory systems in a regulation of the feeding reactions of the horse-flies is
      discussed.

PMID- 14658309
TI  - [The study of the ultrastructure of the female reproductive system in a parasite
      of bats Allassogonoporus amphoraeformis (Digenea: Allassogonoporidae)].
AB  - The morphology and fine structure of the female reproductive system of
      allassogonoporid trematode Allassogonoporus amphoraeformis have been described
      for the first time. The ovary consists of the germ cells being at various
      developmental stages and supporting cells of two types. The oviduct, seminal
      receptacle with its short duct and the proximal portion of Laurer's canal are
      lined by flattened cellular epithelium with lamellae and cilia on its luminal
      surface and well-developed basal infoldings. The distal part of Laurer's canal
      and metraterm are tegumental in structure and are characterized by sparse
      secretory inclusions and lacking of spines. Mehlis' glands of two types open into
      ootype. The uterus wall is composed of highly flattened epithelial cells
      surrounded by basal lamina and sparse muscle bundles. Vitelline lobules consist
      only of the vitelline cells at various developmental stages. The mature vitelline
      cells contain two types of inclusions: vitelline droplets and rarely scattered
      lipids. Vitelline ducts are lined by cellular epithelium with highly folded
      luminal surface and devoid of cilia. Presented results are compared with earlier
      obtained data on other lecithodendrioiden trematode Prosthodendrium ascidia
      ([symbol: see text], 1990).

PMID- 14658310
TI  - [Ultrastructure of the surface complex of acanthocephalans with the example of
      Filicollis anatis (Palaeacanthocephala: Polymorphidae) and Neoechinorhynchus
      crassus (Eoacanthocephala: Neoechinorhynchidae)].
AB  - Fine morphology of external tegument (surface complex) of young and mature
      acanthocephalans Filicollis anatis and young Neoechinorhynchus crassus is
      described. Based on comparative analysis of the obtained results and literature
      data, the surface complex of all examined acanthocephalans is shown to have
      principally similar structure at all stages of life cycle. Differences between
      species examined are found in quantitative characters only and they are related
      either to age or ecology of worms (embryonic larvae).

PMID- 14658311
TI  - [The use of the probability model for an estimation of a infection rate of White
      Sea mussels (MYtilus edulis) by Metacercariae Himasthla elongata (Trematoda:
      Echinostomidae) ].
AB  - A comparison of simple probability analytic model of infection rate depending on
      host's age with natural infection rate of mussels (Bivalvia: Mythilidae) with
      metacercariae Himasthla elongata (Trematoda: Echinostomidae) was carried out.
      Data on the natural rate of infection were accumulated during 3 years; 1152
      individuals M. edulis were collected in two horizons within fucoid zone of the
      Kruglaya inlet and the Chupa inlet of the Kandalaksha bay (White Sea). A size of
      shell and number of H. elongata metacercariae were defined for each mussel using
      compressive dissection technique. The infection of mussels per year within our
      model is considers as independent evens: Pn = 1 - (1 - p)n, where n is the age of
      mussels, Pn is the theoretical part of infected n-year mussels, p is the
      probability of infection within one year. The probability of infection within
      year is assumed equal for every age of host. The estimate of probability of
      infection per year on the basis of sample of n-year's mussels was calculated as
      Pn = 1 - n square root of 1 - I(n), where n is the age of mussels, I(n) is the
      part of infected n-year mussels. The retransformed weighted average value of
      aresine-transformed p'n was used as p in our model (p = 0.3476). Statistically
      significant differences between empirical and theoretical (calculated from our
      models on the basis this value) infection rates were not found (P > > 0.05 chi 2
      test). Moreover, statistical significant differences were absent (P > 0.05 Fisher
      exact test) in pairwise comparisons between empirical and theoretical infection
      rates for each age of mussels. The model does not take into consideration an
      effect of such factors as host's resistance, host's migration and increase of
      mortality in infected hosts. The absence of significant differences between the
      empirical and theoretical infection rates allows to suggest, that mentioned
      factors under the conditions of the Kruglaya inlet do not influence essentially
      onto infection of mussels with metacercariae H. elongata. This conclusions is in
      certain inconsistency with essential differences in such characteristic as an
      individual resistance of mussels to the infection with metacercariae H. elongata,
      detected in experiments in vitro (Gorbushin, Levakin, unpublished data). Analysis
      of intensity of the invasion of metacercariae H. elongata into mussels allows to
      suggest the existence of differential death rate of the hosts, which is exhibited
      in individuals over 7 years old. Studied example of mussels infected with
      metacercariae H. elongata under conditions of the Kruglaya inlet shows that the
      simple probabilistic model of the natural infection rate is usable for this kind
      of investigation. Our study also allows to conclude that in this case the
      infection rate of hosts is mainly determined by stochastic reasons. However, in
      some cases the probability of infection rate may not depend on the age and size
      of the host. The study of infection rate can not be used for analyses of
      individual differences of hosts in a resistance to parasites and an infection
      ability of the parasite.

PMID- 14658312
TI  - [On a life cycle of Unciunia raymondi (Cestoda: Cyclophyllidea: Dilepididae)].
AB  - Cysticercoids of the cestode Unciunia raymondi Gigon et Beuret, 1991
      (Cyclophyllidea: Dilepididae), a parasites of palaearctic thrushes (Turdus),
      taken from spontaneously infected Geotrupes and black wireworm Cylindrojulus in
      the North-eastern Altai, is described. An identity of cysticercoids of U.
      raymondi and Ditestolepis diaphana sensu Kisilewska, 1960 has been stated. During
      the development within the fibrillate membrane, the metacestode of U. raymondi
      separates the cercomer from the cyst anlage in the late scolexogenesis. There is
      no the primary lacuna in the lamellated cercomer without any musculature. Its
      primarily smooth surface gradually becomes sulcate and plicate. In the result of
      some segments break-up, the cercomer lamella comes to be perforated with its
      margins deeply jagged. Metacestode of U. raymondi metacestode is compared with
      cryptocercus of Dilepididae, which also develops within the fibrillate membrane.
      Based on peculiarities of the morphogenesis of cercomer, the cysticercoid U.
      raymondi is assigned to a new morpho-ecological type, the placocercus.

PMID- 14658313
TI  - [Orthonectida's life cycle].
AB  - Analysis of original and literary data permits to conclude that the life cycle in
      Orthonectida may be characterized as a monohost--monoxenous one, including
      regular interchange of three generations: asexual and parthenogenetic ones, which
      are represented by parasitic plasmodiums, and sexual generation, represented by
      free living and non-feeding males and females or, rarely, hermaphrodites. The
      sexual individuals are bilaterial, while the parasitic ones are anaxonic. The
      life cycle of Orthonectida includes the agamic reproduction, apomictic
      parthenogenesis and sexual reproduction regularly following one another. The life
      cycle of Orthonectida can be considered as a combination of metagenesis and
      heterogony. So far, such combination has not been described in any group of
      metazoan parasites.

PMID- 14658314
TI  - [The role of microsporidia in the disturbance of the hormonal balance in the
      infected insects].
AB  - Since investigations of Fisher and Sanborn (1964), the most popular point of view
      on pathological alterations in the development of insects is the statement that
      microsporidians can produce and secrete the insect juvenile hormone in infected
      tissues. We suppose that the juvenilizing effect of microsoporidian infection may
      be a consequence of stress induced by the protozoan invasion. To our opinion,
      microsporidians can not be a source of juvenile hormone in parasitized insects
      because of several reasons. 1. The juvenilizing effect of infection may be
      explained by other reason, that is the stress effect of invasion. 2. Until now
      nobody can find juvenile hormone in microsporidians. 3. An increase of juvenile
      hormone titre either alters non-metabolic activity of fat body or alters it in a
      way that is not favorable for microsporidias. 4. Some effects of the
      microsporidian infection more resemble an action of ecdysone, but not juvenile
      hormone. Hypothesis of parasitic stress can explain this, while hypothesis of
      production JH by microsporidians can not. 5. An effect of invasion by parasites
      of other systematic groups onto the hormone balance is of the same type. But
      nobody thinks that other parasites can produce juvenile hormone. Nevertheless it
      is clear that a high titre of the juvenile hormone is favorable for the
      microsporidian infection in larvae, especially the last instars. The most
      descriptions of microsporidian infections are related with this age of insects.
      Juvenilizing effect of Nosema implantant in the work of Fisher and Sanborn (1964)
      may be easily explained by decreasing of JH-esterase activity. But in this case
      the decrease of JH-esterase activity after the implantation of infected tissue in
      a healthy insect should be explained. We suppose that this fact witness the
      existence of stress-factor produced by damaged cells of fat body that can enter
      the healthy cells of fat body and inhibit the activity of JH-esterases.

PMID- 14658315
TI  - [A description of the new species of Tetraonchus strelkowi sp.n. (Monogenea:
      Tetraonchidae) from gills of the lenok (Brachymastix lenok) from the Tola river
      (Mongolia) ].
AB  - Tetraonchus strelkowi sp. n. described from gills of the lenok Brachymastix lenok
      from the Tola river (Mongolia) differs from T. roytmani by morphometric
      characteristics of the haptor and copulatory complex.

PMID- 14658316
TI  - [Humoral factor dependence of neuronal post-theta choline-sensitive potentiation
      in Helix Lucorum].
AB  - Comparison of posttetanic changes of the acetylcholine-induced inward current
      (ACh-current) in command Helix lucorum neurones at different conditions (using
      stop flow of saline through the chamber with a ganglia preparation and using flow
      of saline) was made. Flow of saline reduces latency and degree of posttetanic
      increase of the ACh-current in neurones. Earlier and weak posttetanic
      potentiation of the ACh-current in command Helix lucorum neurones during flow of
      saline through the chamber with a ganglia preparation testifies to participation
      of the humoral factor in the mechanism of posttetanic potentiation of
      cholinosensitivity of somatic membrane in postsynaptic neurone.

PMID- 14658317
TI  - [Caspase-3 inhibition blocks long-term potentiation in hippocampal slices].
AB  - Incubation of hippocampal slices with Z-DEVD-FMK, a specific inhibitor of caspase
      3, elicits a time dependent decrease in long-term potentiation (LTP). After 4
      hours or later after the incubation with Z-DEVD-FMK the tetanization fails to
      induce LTP. However, Z-DEVD-FMK does not affect basal indices of synaptic
      plasticity and short-term plasticity (population spike amplitudes and paired
      pulse facilitation). The results are the first evidence for the involvement of
      caspase-3-mediated mechanisms in long-term potentiation phenomenon.

PMID- 14658318
TI  - [Selective attention and memory: evoked potentials in visual and auditory verbal
      competition].
AB  - The brain mechanisms of the selective verbal attention were studied using evoked
      potential (EP) technique. It was shown that the late "cognitive" EP components
      (400-800 ms) related to memory function were more positive to the words presented
      via a relevant sensory channel and more negative to irrelevant words. The
      hypothesis is advanced that words delivered via two competing sensory channels,
      such as visual and auditory, are perceived, i.e., the subject sees and hears
      them. However, irrelevant signals are not stored in episodic memory due to the
      active inhibition of the information transmission to the hippocampal structures.

PMID- 14658319
TI  - [Sex differences in EEG power changes in retention of dichotically and monaurally
      presented verbal stimuli].
AB  - EEG power mapping was used to study gender differences in hemispheric functional
      organization during memorizing dichotically and monaurally presented verbal
      information. Right-handed students (12 men and 14 women) participated in
      experiments. The EEG was recorded from 16 electrodes placed at homologous sites
      of the left and right brain hemispheres. Task-related changes in the thetal power
      in men differentiated between monaural presentations to different ears, i.e.,
      situations of oppositely directed attention. In women the thetal power reactivity
      (the difference between the band power logarithms under baseline conditions and
      in task interval) differentiated between dichotic and monaural presentations of
      words, i.e., situations with different memory loads. Gender differences were also
      found in the alpha frequency band. Power changes in the alpha 1 band in all
      memory tasks and power changes in the alpha 2 were more evident in the right
      hemisphere in men but in the left hemisphere in women. In contrast, in the
      posterior temporal lead the alpha 2 power reactivity in men was higher in the
      right hemisphere, whereas in women the lateral differences were absent. As
      compared to men, the alpha 2 desynchronization in women was also more pronounced
      in posterior regions of both hemispheres. There were no gender differences in
      efficacy of memorizing. It is suggested that different processing strategies
      rather than different behavioral performance may be responsible for the revealed
      specific spatiotemporal EEG patterns.

PMID- 14658320
TI  - [Ontogeny-specific interaction of psychophysiological mechanisms of emotional
      perception and educational achievement in students].
AB  - In order to explore the process of adaptation of children to school environment
      psychophysiological characteristics of perception of emotional speech information
      and school progress were experimentally studied. Forty-six schoolchildren of
      three age groups (7-10, 11-13, and 14-17 years old) participated in the study. In
      experimental session, a test sentence was presented to a subject through
      headphones with two emotional intonations (joy and anger) and without emotional
      expression. A subject had to recognize the type of emotion. His/her answers were
      recorded. School progress was determined by year grades in Russian, foreign
      language, and mathematics. Analysis of variance and linear regression analysis
      showed that ontogenetic features of a correlation between psychophysiological
      mechanisms of emotion recognition and school progress were gender- and subject
      dependent. This correlation was stronger in 7-13-year-old children than in senior
      children. This age boundary was passed by the girls earlier than by the boys.

PMID- 14658321
TI  - [The effect of pre-test verbal instruction on spatial organization of cortical
      electrical activity].
AB  - Analysis of coherence of cortical electric activity performed in 30 healthy
      subjects revealed changes in the spatial organization of cortical electric
      activity after listening the instruction, i.e., loading the explicit working
      memory with a sequence of operations of the cognitive task to be solved in the
      course of the experiment. Comparison of instructions presenting several cognitive
      tasks showed that greater load of the working memory is associated with higher
      coherence of cortical activity, especially, in the parietotemporal and occipital
      areas.

PMID- 14658322
TI  - [Dipole models of alpha-rhythm generators].
AB  - Different hypothesis of the alpha rhythm origin were tested by dipole simulation
      of the alpha rhythm sources. EEG was recorded during driving photic stimulation
      in order to increase the signal-to-noise ratio. Models with fixed and moving
      dipoles were analyzed. Dipole sources were compared with magnetic resonance
      imaging (MRI) scans to find the exact location of oscillations in brain
      anatomical structures. A two-level multiple dipole model was found to fit the EEG
      most adequately. The first level was represented by two oscillators localized in
      the thalamic reticular nuclei, and the second level is associated with two
      modality-specific oscillators localized in the respective cortical areas.

PMID- 14658323
TI  - [Changes in anxiety level of Wistar rats under the influence of maximally-diluted
      solution of a plant alkaloid].
AB  - A very dilute solution of Nux Vomica 200 plant alkaloid was applied onto the
      tongue of Wistar rats. The level of rats' anxiety was estimated by their behavior
      in elevated plus-maze. The dry application led to substantial changes in rats'
      behavior. In "passive" rats previously defined by the forced swimming tests
      changes in behavior were most prominent. The possible influence of the drug under
      study on the adaptive abilities of this group of animals is discussed.

PMID- 14658324
TI  - [Extinction and amnesia in aggressive and submissive mice with various terms of
      agonistic interaction].
AB  - Dependence of the passive avoidance retrieval on the duration of agonistic
      interactions was analyzed in C57BL/6J mice in procedures of extinction and
      amnesia during formation of aggressive and submissive behavioral stereotypes. The
      resistance to amnestic stimulation was lower in aggressive mice with 10-day
      experience of victories than in aggressive animals after 20 daily confrontations.
      Prolongation of extinction in aggressive mice and fast extinction in submissive
      animals did not depend on the number of agonistic interactions.

PMID- 14658325
TI  - [The role of electrophysiological properties of neurons in mechanisms of
      discharge grouping in the cortex].
AB  - Properties of intracellular discharges of pyramidal cells of layers II/III and V
      in rat neocortex were in detail studied in vitro. Neuronal firing was evoked by
      depolarizing 1-3-min current injection (0.1-1.0 nA) into the neurons (N = 80).
      The so-called spike sequences with regular increasing or decreasing interspike
      intervals were analyzed. Number of spikes in a sequence (5-30% of recorded total
      spike number) and oscillation amplitude of their afterhyperpolarization potential
      (0-1.5 mV) were significantly correlated with their mean firing frequency. The
      dependence of spike number in a sequence on the mean spike frequency was of
      biphasic character with the critical frequency in the range of 5-7 Hz. Cells with
      and without depolarization component during afterhyperpolarization had different
      morphological and electrophysiological properties, but the dependence of their
      spike number in a sequence on the spike mean frequency was of similar character.
      A possible role of the revealed characteristics of spike sequences in generation
      of cortical rhythms is discussed.

PMID- 14658326
TI  - [Age-specific morphological-functional characteristics of the rabbit's
      hippocampal neurons during conditioning].
AB  - Formation of trace rhythm recruitment (an analogue of conditioned time reflex)
      was studies in CA3 hippocampal neurons of alert young (less than one year), old
      (54-65 months), and very old rabbits after a prolonged (10-20 min) electro
      cutaneous stimulation of a forelimb with the frequency of 0.5-1 Hz. Comparative
      analysis of neuronal spike activity in young and old rabbits showed that in the
      late ontogeny the number of spontaneously active neurons was significantly
      decreased, the proportion of slowly firing neurons increased, the interspike
      intervals and intervals between spike groups became longer, the number of spikes
      in a group reduced. The ability of hippocampal neurons to acquire and reproduce
      the rhythm of the previous stimulation declined with age. No appropriate rhythms
      were found in neurons of very old animals. A nonspecific increase in neuronal
      baseline activity was observed in old rabbits after the stimulation.
      Deterioration of morphological structures of hippocampal neurons and glial cells
      may explain the impairment of mnestic processes in late ontogeny.

PMID- 14658327
TI  - [Specifics of post-theta modification of synaptic transmission in thalamo
      cortical input of the rat's barrel cortex].
AB  - The possibility of the development of either the long-term posttetanic
      potentiation or the depression of focal evoked potentials in identified columns
      of the barrel somatic cortex of unanaesthetized rats during stimulation of their
      specific thalamocortical afferent fibers was shown. Phase-dependent potentiation
      developed after burst tetanization with the frequency of theta rhythm at the
      negative phase of a theta wave, whereas the stimulation at the positive phase
      produced the depression. Potentiation after continuous tetanization was observed
      only at the optimal selection of stimuli amplitude and duration. Excessively
      intense tetanization more frequently caused the depression of tested responses
      probably due to the involvement of recurrent inhibition.

PMID- 14658328
TI  - [Neuronal activity in the nucleus basalis magnocellularis during performance of
      an instrumental task].
AB  - Spike activity of 95 neurons in the rabbit basal forebrain forebrain
      magnocellular nucleus was recorded during spontaneous behavior and instrumental
      conditioned performance. Almost half of the neurons (48.4%) displayed a
      significant (p > 0.05) negative correlation between their spontaneous discharge
      rate and the power of the delta rhythm in the EEG of the frontal cortex; most of
      these cells can be classified as projection cholinergic neurons. During
      instrumental conditioned performance, neurons of this subgroup responded with
      excitation to the conditioned stimulus, whereas presumably noncholinergic
      nonprojection neurons responded to the conditioned stimulus with inhibition.
      Excitatory response of cells in the basal forebrain magnocellular nucleus was
      significantly more intense as compared to trials without the conditioned
      reaction. On the whole, our data testify that the basal forebrain magnocellular
      nucleus maintains the level of arousal and attention required for the
      instrumental conditioned performance.

PMID- 14658329
TI  - [Cortical alpha-2a adrenoreceptors involved in the inhibitory control of motor
      activity in neonatal rats].
AB  - Involvement of alpha 2A-adrenoceptors in control of motor activity in neonatal
      rats was investigated using intrabrain injections of antisense
      deoxyoligonucleotide targeting mRNA of these receptors. Antisense-induced
      decrease in the receptor expression in the brain accompanied by an augmentation
      of animal's motor activity, which was evaluated as a number of paddling movements
      with the right forepaw. This antisense effect was stimulatory and was not related
      to somatic growth and maturation of reflexes in the animals. The antisensetreated
      pups differed from controls neither in body weight nor the latency of righting
      reflex. The data suggest that alpha 2A-adrenoceptors are involved in inhibitory
      control of motor activity of rat pups from the first day of life.

PMID- 14658330
TI  - Stimulation of the lateral hypothalamus provokes the initiation of robust long
      term potentiation of the thalamo-cortical input to the barrel field of the adult,
      freely moving rat.
AB  - Long-term potentiation in the thalamo-cortical input to the somatosensory cortex
      barrel field has been reported to be inducible in vitro only during a narrow
      critical period of the first postnatal week. Here we explored whether this is due
      to inability of adult synapses to express LTP or lack of appropriate conditions
      for LTP induction in slice preparations. We recorded thalamo-cortical field
      potentials (FPs) from the barrel field of chronically prepared adult rats. In the
      first series, several parameters of conditioning tetanization of thalamus (T)
      have been tried. Statistically significant LTP of 135-150% relative to the
      baseline was observed only in rare cases (3/18) so that the mean changes were not
      statistically significant. In the second series, five trains of 100 Hz
      stimulation of T were paired with a "reinforcing" stimulation of the lateral
      hypothalamus (LH). In most cases (9/13) thalamo-cortical FPs were potentiated.
      The mean post-tetanic amplitude was 238 +/- 42% (+/- SEM) relative to the
      baseline (n = 13). The potentiation persisted for > > 1 hr and typically even
      further increased when tested 24-48 hr later. LTP magnitude strongly correlated
      with the initial paired-pulse ratio (PPR, coefficient of correlation r = 0.98) so
      that LTP magnitude was larger (333 +/- 107, n = 6) in cases with PPR > 1.3. The
      mean PPR tended to decrease after LTP (from 2.05 to 1.65). Altogether the results
      suggest that LTP is inducible in the thalamo-cortical input to the barrel field
      of normal adult rats. The dependence of LTP magnitude upon the initial PPR
      suggests that inputs with low initial release probability undergo larger LTP.
      Together with the tendency to a decrease in the PPR this suggests an involvement
      of presynaptic mechanisms in the maintenance of neocortical LTP.

PMID- 14658331
TI  - [Serotonin reuptake blocker fluoxetine suppresses hippocampal theta oscillation
      in rabbits during EEG].
AB  - In earlier studies it has been shown that stimulation of the median raphe nucleus
      (MR) in awake rabbits decreases the expression and frequency of oscillatory theta
      activity in the septohippocampal system, and the functional blockade of this
      nucleus evokes the regular and high-frequency theta rhythm. The present work was
      aimed at elucidation of serotoninergic influence of MR (which also contains cells
      of other chemical nature) to the septohippocampal system of theta activity.
      Serotonin reuptake blocker fluoxetine that increases brain serotonin level was
      applied. Hippocampal electroencephalogram was recorded in awake rabbits.
      Bilateral intracerebroventricular infusion of fluoxetine hydrochloride (Sigma,
      St. Louis; 15 micrograms in 5 microliters saline) in all cases reduced the
      rhythmic theta activity. In 15 of 18 (83.3%) of experiments the decrease in
      hippocampal theta oscillations was more than 50% of the control level. The theta
      band of the spectral density histogram decreased in the mean by 56 +/- 5.8% of
      the control level (from 10 to 93% in different experiments, p < 0.001). The mean
      latency of these changes was 3.5 +/- 0.11 minutes (2.9-4.1 min), the effect
      duration was 64 +/- 3.2 min (45.3-90 min). The mean frequency of the theta waves
      did not change as compared to the baseline and was equal to 5.25 +/- 0.5 Hz (4.5
      6.5 Hz). The fluoxetine-induced reduction of the theta rhythm expression in
      hippocampus is the evidence of its inhibitory control by serotoninergic brain
      system. It is suggested that the increase of the frequency of hippocampal theta
      rhythm after the functional blockade of MR observed in our earlier experiments
      was the result of a release of the septohippocampal system from the influence of
      nonserotoninergic neurons (via glutamatergic reticular formation) and/or
      temporary cessation of the MR interaction with noradrenergic, dopaminergic and
      glutamate/aspartate systems.

PMID- 14658332
TI  - [Low dose of disulfiram and l-dopa evoked synergistic modification in behavior of
      Wistar and WAG/Rij rats].
AB  - Comparative analysis of behaviors of two rat strains, Wistar and WAG/Rij, was
      performed. No behavioral differences between Wistar and WAG/Rij were found in the
      emotional resonance test. Disulfiram injection produced similar effects in both
      rat strains. Animals of the first group (with slow acquisition of emotional
      resonance reaction) transformed into the animals of the second group (with fast
      acquisition). Passive avoidance conditioning was successfully reproduced in
      Wistar and was significantly impaired in WAG/Rij. A low dose of disulfiram
      injected before or immediately after conditioning substantially improved the
      reproduction to a greater extent in WAG/Rij than Wistar strains thus eliminating
      in interstrain differences. Active avoidance conditioning was more successful in
      WAG/Rij than in Wistar rats However, on the next day conditioning in WAG/Rij was
      substantially impaired. Administration of the low dose of disulfiram or L-DOPA
      prior to conditioning impaired the acquisition but improved the reproduction on
      the following day in both strains, but disulfiram injection after conditioning
      improved conditioning in WAG/Rij to a greater extent than in Wistar. Thus, the
      pharmacologic enhancement of the reward system substantially changed animal
      behavior and improved memory consolidation.

PMID- 14658334
TI  - [SMC (structural maintenance of chromosomes) structural protein family and their
      role in chromatin reorganization].
AB  - Structural chromatin proteins of the SMC (Structural Maintenance of Chromosomes)
      family play an important role in structural DNA reorganization in pro- and
      eukaryotes. Eukaryotic SMC proteins are the core components of the cohesin and
      condensin complexes. The cohesin complex is responsible for sister chromatid and
      homolog cohesion in mitosis and meiosis. The condensin complex uses ATP energy to
      induce positive coiled-coils in DNA, which results in compaction of the latter
      and formation of mitotic chromosome scaffold. In addition, the SMC proteins
      constitute recombination and recombination repair complexes. In hermaphrodites of
      nematode Caenorhabditis elegans, the SMC protein-containing complex controls
      dosage compensation and inactivation of the X chromosome genes.

PMID- 14658333
TI  - Altered neuronal responses to feeding-relevant peptides as sign of developmental
      plasticity in the hypothalamic regulatory system of body weight.
AB  - Neuronal plasticity during the critical postnatal period of development seems to
      promote a change in the function of the hypothalamic regulatory system of body
      weight. Rats raised in small litters (SL) of only three pups per mother compared
      to ten or twelve in control litters (CL) gain significantly more weight than
      normal rats till weaning and are overweight also in later life. These rats are
      known to express hyperleptinemia, hyperglycemia and hyperinsulinemia. The review
      summarizes the results of action of leptin and insulin as well as of several
      feeding-relevant neuropeptides on neuronal activity of hypothalamic regulatory
      centres in overweight SL rats compared to controls. The study was performed on
      brain slices perfused with solution containing 10 mM glucose. Whereas a normally
      inhibitory action of leptin and insulin on medial arcuate neurons (ArcM) is
      reduced in SL rats and partly replaced by activation, the normally activating
      effect of these hormones on ventromedial (VMH) neurons is altered to predominant
      inhibition. Inhibition of ArcM neurons may decrease the release of the orexigenic
      neuropeptide Y (NPY) and agouti gene-related protein (AGRP). Thus, the negative
      feedback by leptin and insulin on food intake is replaced by diminished response
      and partly positive feedback processes in SL rats. The action of NPY and AGRP as
      well as of the orexigenic melanin-concentrating hormone on paraventricular (PVH)
      and VMH neurons is also shaped from activation or bimodal effects to predominant
      inhibition. Such inhibition of PVH and VMH might lead to reduced energy
      expenditure in small litter rats. Also the anorexigenic melanocortin alpha-MSH
      seems to contribute into increased energy storage. These altered responses of
      hypothalamic neurons in overweight small litter rats might reflect a general
      mechanism of neurochemical plasticity and "malprogramming" of hypothalamic
      neuropeptidergic systems leading to a permanently altered regulatory function.

PMID- 14658335
TI  - [Use of suppressor subtraction hybridization for finding strain-specific
      sequences in bacterial genomes].
AB  - Comparisons of bacterial genomes demonstrate that even strains of one species may
      strikingly differ in gene set. Strain-specific genes are of considerable
      interest, as they may be responsible for distinguishing features, such as
      virulence or drug resistance, of the strain and may be employed as markers in
      epidemiological or evolutionary studies. Suppression subtractive hybridization
      (SSH) was shown to be suitable for generating a set of DNA fragments differing
      between two closely related bacterial strains. More than 95% DNA fragments
      selected by SSH proved to be specific for Staphylococcus aureus strains ZW
      compared with strain 29213.

PMID- 14658336
TI  - [Reconstruction of the phylogenetic position of larch (Larix sukaczewii Dylis) by
      sequencing data for the trnK intron of chloroplast DNA].
AB  - To reconstruct the systematic relationships of larch Larix sukaczewii, we used
      the chloroplast trnK intron sequences of L. decidua, L. sukaczewii, L. sibirica,
      L. czekanovskii, and L. gmelinii. Analysis of phylogenetic trees constructed
      using the maximum parsimony and maximum likelihood methods showed a clear
      divergence of the trnK intron sequences between L. sukaczewii and L. sibirica.
      This divergence reaches intraspecific level, which supports a previously
      published hypothesis on the taxonomic isolation of L. sukaczewii.

PMID- 14658337
TI  - [Inheritance and expression of gametophyte gene Adh-P causing modification of
      alcohol dehydrogenase in pollen grains of the beet (Beta vulgaris L.)].
AB  - An additional alcohol dehydrogenase (ADH) activity zone denoted ADH-P ("pollen")
      has a slightly lower mobility than the major protein ADH1 (the product of
      structural locus Adh1). This zone is detected in maturing and mature pollen
      grains and has not been found in any other tissue. ADH-P is detected by
      electrophoresis in a neutral medium (at pH 7.0-7.2). In an alkaline medium (pH >
      8), protein ADH-P is completely inactivated, whereas protein ADH1 retains its
      activity. ADH-P is a modified variant of the major protein ADH1. Both alleles of
      the main structural gene (Adh1-F and Adh1-S) undergo modification. The pollen of
      an FS heterozygote has two variants of the modified enzyme: ADH-PS and ADH-PF.
      Analysis of segregation in F2 offsprings and test crosses has confirmed that this
      character is controlled by the only gene Adh-P with allelic variants Adh-P+ (the
      presence of the modified ADH protein in the pollen) and Adh-P- (the normal
      protein). Allele Adh-P+ is transmitted through female gametes at a normal
      frequency (about 1) and through male gametes at a decreased frequency (0.2-0.6),
      the mean frequency being about 0.4. The frequency of the transmission of allele
      Adh-P+ through male gametes depends on the genotype of the female parent and the
      conditions of pollination. Cytoembryological study of microsporogenesis in the
      Adh-P+/Adh-P- heterozygotes demonstrated an absence of any disturbances in the
      formation of microspores and pollen grains. Some differences in the formation of
      pollen tubes on an artificial medium have been observed. It is assumed that the
      differences between the Adh-P+ and Adh-P- microgametophytes manifest themselves
      at the progamic phase of fertilization. The possible mechanisms of the formation
      of the modified ADH-P protein are discussed in connection with the differential
      activity of genes in the microgametophytes of angiosperms.

PMID- 14658338
TI  - [Dynamics of genetic variation of Sartov cultivars of common wheat Triticum
      aestivum L. (from the gliadin-coding locus) after a an 80-year period of
      scientific selection].
AB  - Based on analysis of gliadin patterns in common wheat cultivars developed at the
      Research Institute of Agriculture of the Southeast, profile dynamics in gliadin
      loci has been surveyed for the period of over eight decades. It was shown that
      long-term breeding of the wheat cultivars involved gradual replacement of alleles
      characteristic of ancient cultivars for those widely spread in the world, which
      are probably linked with alleles that currently confer advantage to their
      carriers. The process of reduction of inter-population genetic diversity in wheat
      (with special reference to the allele frequency dynamics at gliadin loci) is
      discussed. This process is responsible for genetic erosion of the species.

PMID- 14658339
TI  - [Induction of dominant lethals in progeny of male CBA mice after pheromonal
      action].
AB  - The inhibiting effect of pheromone 2,5-dimethylpyrazine of house mouse females on
      the reproductive function of the CBA male mice was studied. The mutagenic effect
      of six-day pheromonal effect was assessed by dominant lethal test. Analysis for
      the frequency of dominant lethals showed that the pheromonal effect results in an
      increased death rate of the progeny of the treated males. This is probably
      explained by implantation failure and is expressed in a reduced average number of
      the implantation sites and low live embryos per female. The proportion of females
      with live embryos decreased significantly. The implication of the effect of
      female mouse pheromone 2,5-dimethylpyrazine on the genetic processes in germ
      cells of male mice is discussed.

PMID- 14658340
TI  - [Low genetic differentiation and close evolutionary connection between Anas
      platyrhynchos and Anas poecilorhyncha: data from RAPD-PCR analysis].
AB  - Using RAPD-PCR, we examined genetic diversity and phylogenetic relationships in
      two groups of river ducks: Anas platyrhynchos, A. poecilorhyncha, A. strepera and
      A. crecca, A. formosa, A. querquedula. Molecular taxon-specific markers were
      found for teals (A. crecca, A. formosa, A. querquedula) and gadwall (A.
      strepera). Each of the species examined was shown to exhibit high genetic
      diversity. The mean levels of intraspecific genetic polymorphism in the groups of
      mallards (P = 77%) and teals (P = 74.5%) were approximately equal whereas the
      mean interspecific genetic distances in teals were significantly higher than in
      mallards (D = 0.432 and D = 0.336, respectively). The levels of interspecific
      genetic differentiation in the species groups were also different. The genetic
      distances between the teal species and between gadwall and mallards were equal to
      0.668-0.971 while the genetic distance between mallard A. platyrhynchos and spot
      billed duck A. poecilorhyncha was 0.401, which slightly exceeds the intraspecific
      values for mallards (0.356-0.377). The RAPD patterns for this species pair showed
      high variability and a lack of fixed differences. This was adequately reflected
      on both intra- and interspecific differences and on phylogenetic constructions in
      which the morphological species did not form their own clusters but were
      intermixed. In contrast to mallards, the other species, which showed high genetic
      variability, were reliably separated in phenogenetic and phylogenetic
      reconstructions. The possible explanations of the low genetic differentiation of
      A. platyrhynchos and A. poecilorhyncha are discussed.

PMID- 14658341
TI  - [Genogeographic variability and genetic differentiation of the root vole
      (Microtus oeconomus Pallas, 1776, Cricetidae, Rodentia) from the Kuril Islands].
AB  - Electrophoretic analysis of 12 enzyme systems and 3 nonenzyme proteins (in all,
      24 interpretable loci) was carried out for Microtus oeconomus from ten Kuril
      islands, Kamchatka Peninsula, and the vicinity of the city of Magadan. Gene
      geographic variation was examined and the coefficients of genetic variation and
      differentiation were estimated. The inter-population allozyme differentiation was
      low (DNEI, 1972 not higher than 0.053) and caused by variation in the allele
      frequencies of polymorphic loci. The greatest genetic distances were found
      between the populations belonging to different subspecies. Allozyme
      differentiation of Far Eastern M. oeconomus and M. fortis are discussed in
      relation to the data on the age of the island isolation and paleontological
      records. Karyological analysis (G-, C-, and NOR-banding) demonstrated the absence
      of differences between M. oeconomus from Kamchatka and the vicinity of Magadan.

PMID- 14658342
TI  - [Quantitative characteristics of the frequency of chromosomal aberrations in a
      group of residents of a large western Siberian industrial region].
AB  - The results of a 15-year study of chromosome aberration frequency in cultured
      peripheral blood lymphocytes from subjects living in the Kuzbass industrial
      region are presented. The database for the analysis of the main parameters of
      chromosome aberrations contains data on 925 subjects, with the total number of
      cells examined being 92,900. It has been found that the total frequency of
      aberrant metaphases in the database is 3.73 +/- 0.1%, whereas this frequency for
      the sample of subjects from industrial areas of this region (the basic control
      group) is significantly lower (2.86 +/- 0.26%). It has been demonstrated that the
      sex and age of the subjects do not affect substantially the frequency of any type
      of chromosome aberrations. Tobacco smoking is associated with a slight increase
      in chromosome damage frequency; however, the difference between smokers and
      nonsmokers is insignificant even among subjects exposed to occupational hazards.
      The possible causes that have determined the increased basic and background
      chromosome aberration frequencies in the population of the Kemerovo oblast
      compared to these parameters for the European part of Russia and the CIS are
      discussed.

PMID- 14658343
TI  - [Analysis of genetic diversity of population of Northern Eurasia from autosomal
      microsatellite loci].
AB  - The paper presents the results of analysis of the gene pools of several North
      Eurasian ethnic groups (Buryats, Evenks, Altaians, Russians, Kyrgyzes, Tuvinians,
      Tatars, and Ukrainians) examined using a panel of autosomal microsatellite
      markers (D4S397, D5S393, D7S640, D8S514, D9S161, D10S197, D11S1358, D12S364, and
      D13S173) mapped on different chromosomes and represented by the (CA)n
      dinucleotide repeats. In the group of populations examined the proportion of
      genetic variability at microsatellite loci explained by interpopulation
      differences was about 2.5%, while genetic differences between the individuals
      within a population accounted for 97.5% of this variability. Analysis of genetic
      relationships among the populations revealed substantial differences between the
      populations belonging to the Indo-European and Altaic linguistic families in gene
      diversity at microsatellite loci.

PMID- 14658344
TI  - [Genetic differentiation of residents of Central Asia from autosomal marker
      data].
AB  - The gene pool of five ethnic groups of the Central Asian population was
      characterized using nine human-specific polymorphic insertion/deletion loci (ACE,
      PLAT, APOA1, PV92, F13B, A25, B65, CD4, Mt-Nuc). It has been shown for the first
      time that at the CD4 locus, the frequency of Alu(-) is inversely related to the
      Mongoloid component of the population. For the Central Asian populations, the
      lowest and highest frequencies of the Alu deletion at locus CD4 were recorded
      respectively in Dungans (0.04), immigrants from China, and Tajiks (0.15). The
      coefficient of gene differentiation in the Central Asian populations for all the
      genes was 2.8%, which indicates a relatively low level of population genetic
      subdivision in this region. The unity of the gene pool of the Central Asian
      Caucasoids was shown.

PMID- 14658345
TI  - [Polymorphism of six Alu-insertions in residents of Morocco: comparative study in
      Arab and Berber populations and residents of Casablanca].
AB  - Alu elements are the largest family of short tandem interspersed elements (SINEs)
      in human who have arisen to a copy number with an excess of 500,000 copies per
      haploid human genome and mobilize through an RNAse polymerase III derived
      transcript in a process termed "retroposition." Several features make Alu
      insertions a powerful tool used in population genetic studies: the polymorphic
      nature of many Alu insertions, the stability of an Alu insertion event and,
      furthermore, the ancestral state of an Alu insertion is known to be the absence
      (complete and exact) of the Alu element at a particular locus and the presence of
      an Alu insertion at the site that forward mutational change. Here we report on
      the distribution of six polymorphic Alu insertions in a general Moroccan
      population and in the Arab and Berber populations from Morocco and their
      relationships with other populations previously studied. Our results show that
      there is a small difference between Arabs and Berbers and that the Arab
      population was closer to African populations than Berber population which is
      closest to Europeans.

PMID- 14658346
TI  - [Effectiveness of a battery of tests to assess the potential mutagenic danger of
      chemical compounds].
AB  - A new method for assessing the efficiency of batteries of arbitrary numbers of
      tests is proposed. The posterior probability of the mutagenicity of the
      substances studied has been estimated using discriminant analysis. The results of
      tests in each test system has been presented as the probability to obtain a
      positive result in the given test system. This has made it possible to decrease
      the sample size as the number of tests in the battery increased. As a result,
      prognostic power may be assessed even if the matrix of results is incomplete.
      This approach has been used to estimate the weights of evidence for mutagenic
      activities of 105 chemical compounds studied by means of a battery of four tests:
      Ames's test, the test for chromosome aberrations in vitro, the test for
      cytogenetic defects in vivo, and the test for dominant lethal mutations in
      rodents.

PMID- 14658347
TI  - [Quantitative evaluation of gene variation and interpopulation differentiation of
      parthenogenetic species of Darevskia lizards based on mini- and microsatellite
      DNA markers].
AB  - Methods of estimating within- and between-population gene diversity in
      parthenogenetic species using mini- and microsatellite DNA markers and modified
      Wright's FST statistic are presented with special reference to model populations
      of lizards of the genus Darevskia (D. dahli, D. armeniaca, D. unisexualis). We
      used DNA fingerprinting data for several populations of these species examined
      earlier. The effects of variation in M13, minisatellite, (GACA)n and (TCC)n
      microsatellite loci on the formation of within-population gene diversity in
      parthenogenetic species D. dahli and D. armeniaca were shown to be different. The
      equality of the realized gene diversity H and its maximum possible value Hmax in
      two populations of D. dahli (Hmax = 0.032, H = 0.031, P < < 0.0431; Hmax = 0.024,
      H = 0.027, P = 0.09) and D. armeniaca (Hmax = 0.05, H = 0.053, P = 0.03; Hmax =
      0.054, H = 0.055, P = 0.02) suggests that variation in (GACA)n loci substantially
      contributes to the maintenance of within-population genetic diversity. Analysis
      of between-population genetic diversity using loci M13, (GACA)n, and (TCC)n
      showed differentiation of D. dahli populations from northeastern and northwestern
      Armenia (FST = 0.0272, P = 3 x 10(-13)) and genetic homogeneity of the Armenian
      and Introduced to the Ukraine populations of D. armeniaca characteristic of one
      clone (FST = 0, P = 1).

PMID- 14658348
TI  - [Scheme for dispersion analysis for evaluating heritability of reproductive
      traits in medicinal leech Hirudo medicinalis L].
AB  - ANOVA designs for estimating heritabilities of fecundity traits in Hirudo
      medicinalis including batch size, the number of juveniles per cocoon, and
      juvenile weight. Accounting for reproduction mode of this species, different
      types of kinship were identified, which were taken into account in the ANOVA
      designs: juveniles from one batch and one cocoon were considered respectively
      full sibs and polyzygotic twins. Variation components were analyzed in the
      following kinship groups: for batch size, in full sibs; for the number of
      juveniles per cocoon, between sibships, full sins, and replicates; and for
      juvenile weight, in full sibs and polyzygotic twins. Using these designs,
      heritabilities of basic reproductive traits of H. medicinalis were obtained: for
      batch size, h2 = 0.35-0.40, H2 = 0.40-0.45; for the number of juveniles per
      cocoon, h2 = 0.33-0.36, H2 = 0.36-0.39; and for juvenile weight, h2 = 0.40-0.44,
      H2 = 0.44-0.48.

PMID- 14658349
TI  - The paradox of qualitative research design.

PMID- 14658350
TI  - The structure of everyday self-care decision making in chronic illness.
AB  - As health care reform strategists increasingly recognize the critically important
      potential of effective everyday self-care decision making for reducing the burden
      of illness and the strain on health service systems, we must find ways to
      understand and support it. In this study, the authors investigate persons with
      expertise in self-care management of type 2 diabetes, HIV/AIDS, and multiple
      sclerosis to understand how everyday self-care decision making is learned and
      experienced. They used interview, think-aloud, and focus groups to construct an
      account of how persons affected by these chronic diseases make decisions in
      relation to the choices in their everyday lives and learn to manage the untoward
      effects of these conditions according to their unique contexts and values. The
      findings form a conceptual foundation for ongoing inquiry into this complex
      phenomenon and provide insights that might assist clinicians to understand more
      fully the responses and attitudes of those they serve.

PMID- 14658351
TI  - Balancing: a basic process in end-of-life cancer care.
AB  - In this grounded theory study, the authors interviewed caregivers and patients in
      end-of-life cancer care and found Balancing to be a fundamental process
      explaining the problem-solving strategies of most participants and offering a
      comprehensive perspective on both health care in general and end-of-life cancer
      care in particular. Balancing stages were Weighing--sensing needs and wishes
      signaled by patients, gauging them against caregiver resources in diagnosing and
      care planning; Shifting--breaking bad news, changing care places, and treatments;
      and Compensating--controlling symptoms, educating and team-working, prioritizing
      and "stretching" time, innovating care methods, improvising, and maintaining the
      homeostasis of hope. The Balancing outcome is characterized by Compromising, or
      "Walking a fine line," at best an optimized situation, at worst a deceit.

PMID- 14658352
TI  - Advanced prostate cancer patients' ways of coping with the hormonal therapy's
      effect on body, sexuality, and spousal ties.
AB  - The authors examine the coping strategies employed by advanced prostate cancer
      patients receiving hormonal therapy to learn from their experience about
      potential solutions to their nonmedical needs. The study was based on in-depth
      interviews with 15 such patients and data analysis by the constant comparative
      method. The main psychosocial difficulties detected were patients' bodily
      feminization, sexual dysfunction, and disruption of spousal intimacy.
      Participants contended with these difficulties through disguise, diversion, and
      avoidance strategies applied in social interactions, and through self-redefining,
      self-distancing, and self-solacing cognitive tactics. The analysis of these
      coping techniques clarifies the motives behind their adoption by the
      participants, their changing patterns over time, their advantages and
      disadvantages, and the potential that understanding these issues possesses for
      improving interventions aimed at alleviating patients' difficulties.

PMID- 14658353
TI  - Ethnography and measurement in mental health: qualitative validation of a measure
      of continuity of care (CONNECT).
AB  - Ethnography contributes to measure development by enhancing validity and
      providing a basis for qualitative validation. Validating research measures means
      making cases for their "trustworthiness." The authors argue for the
      trustworthiness of CONNECT, a measure of continuity of care, by presenting the
      interpretive logic through which they elaborated continuity for measure
      construction purposes. They used category construction methods to identify
      mechanisms of continuity in ethnographic data. Mechanisms suggested five
      measurement domains: (a) knowledge, (b) flexibility, (c) availability, (d)
      coordination, and (e) transitions. Validation rationales summarize the
      ethnographic evidence and explain how the domain relates to continuity. In making
      explicit the data and the reasoning used, the authors argue for the
      trustworthiness of their interpretation. The arguments for trustworthiness
      demonstrate a qualitative validation process.

PMID- 14658354
TI  - Surgical body modification and altruistic individualism: a case for cyborg ethics
      and methods.
AB  - Three cases of pediatric surgical body modification--limb lengthening,
      normalization of genitalia, and craniofacial surgery--are considered through the
      moral language used by those who experience these surgeries. This language has
      been described as altruistic individualism. Decision making remains
      individualist, but it also shows considerable concern for others; egoism is
      complementary with altruism. The altruistic individualist is one of many
      incompatible identities that are predicted and described by the figure of the
      cyborg. Cyborgs suggest both ethics and qualitative methods appropriate to
      surgically shaped children.

PMID- 14658355
TI  - Using metaphor as a qualitative analytic approach to understand complexity in
      primary care research.
AB  - Metaphors offer exciting opportunities to identify and explore tacit knowledge
      and behavior that are embedded in complex organizations and shape health care
      practices. In this article, the authors explore the theoretical rationale,
      background, and advantages of using metaphor as an analytic strategy in
      qualitative health research. They used an analysis of 18 practices in a
      comparative case study designed to explore office practice strategies for
      delivering cancer prevention services for illustrations. During the individual
      and comparative stages of the analysis process, researchers heeded the metaphors
      that they used in their descriptive language of practices. The authors explore
      examples showing how metaphors clarify unwritten assumptions, values, and
      motivators that shape variations in practice behavior.

PMID- 14658356
TI  - Developing a provisional standard for clinical supervision in nursing and health
      visiting: the methodological trail.
AB  - The authors outline the process that led to the development of a provisional
      professional standard for clinical supervision, focusing on design, data
      collection, and analysis methods. The work was undertaken in an ethos of new
      paradigm/fifth-generation approaches and used the "manifold of subjective
      knowing" to gain a holistic understanding of supervisors' experience as
      represented by experiential, presentational, propositional, and practical
      knowing. They show how they arrived at the indicators of the standard:
      Professional Support, Learning, and Accountability. Each of these indicators
      consists of further elements related to Time, Environment, Relationship
      (Professional Support), Focus, Knowledge, Interventions (Learning),
      Organizational Support, Recording, and Competency (Accountability). Findings
      confirm that clinical supervision practice is complex, and the authors describe
      proportionally complex methods of analysis.

PMID- 14658357
TI  - "Stuck in the middle with you": the ethics and process of qualitative research
      with two people in an intimate relationship.
AB  - In this article, the authors discuss their experiences of two separate research
      projects involving interviews with both partners in care relationships that
      pushed the ethics of research methods along unfamiliar routes. The desire to
      understand the relationship from both sides was seen to outweigh the perils of
      accessing both stories but only when the ethical and procedural elements had been
      sufficiently worked through. It is those ethical and procedural elements that
      they share in this article, which is offered as a provocative nudge toward a
      continued critical appraisal of ethical standards within qualitative research and
      begins with the authors' reflection on their processes for such research through
      the examination of a fictionalized vignette.

PMID- 14658358
TI  - Iceberg ahead?

PMID- 14658359
TI  - What influences the mature consumer?

PMID- 14658360
TI  - A blueprint for the future.

PMID- 14658361
TI  - Marketing for keeps.

PMID- 14658362
TI  - A growing market. As obesity rates rise, so do the opportunities for marketers of
      specialized services.

PMID- 14658363
TI  - [The Free Trade Area of the Americas (FTAA) and the health sector in Latin
      America].
AB  - The Free Trade Area of the Americas-FTAA, which will be implemented in 2005, is
      the closest expression of economic globalization we will have. In this paper the
      debate about the neo liberal tendency of globalization is considered: on one side
      are the defendants of trade, competition and market liberalization; on the other
      side, those who claim for global social justice, for an alternative
      globalization, for reaching the ideal of justice in the planet, seriously
      affected by the free trade agreements, in the absence of a global political power
      capable of distributing richness. The debate permanently animates this essay on
      the FTAA which starts with the government proposals and the scope that the
      interventions of the U.S.A. and the trans-nationals have on the decisions of our
      countries, besides pointing out to the negative effects that the North American
      Free Trade Agreement-NAFTA has had on health. Most of the affirmations on the
      FTAA and its impact on health are derived from its analysis and the new
      relationships imposed on world trade through organisms as the World Trade
      Organization-WTO.

PMID- 14658364
TI  - [Patents in pharmaceutical industry: between ethics and property rights].
AB  - The article presents a reflection on one of the greater challenges which the
      contemporary State is confronted with, related to guaranteeing the effective
      application of the fundamental rights, besides having to solve the conflicts that
      arise due to the rivalry between either fundamental rights or between some of
      these and others known as second or third generation rights. The conflict between
      the protection to the intellectual property rights, as in the case of the patents
      of the pharmaceutical multinationals, and the fundamental right to life is
      considered. It is observed that the interests of these companies have prevailed,
      as if the fundamental value to protect was the profit of these multinationals, or
      their efficiency, and not the right to health of the individuals which bears a
      direct relation with the right to the life. This situation is aggravated still
      more when the State, instead of being on the side of the weaker and offering him
      protection, safeguards the stronger who abuse of their dominant position,
      exerting the monopoly on the production of many essential medicines.

PMID- 14658365
TI  - [Violence management from public health: the Early Prevention Project in
      Medellin].
AB  - Violence is a priority problem in Colombia. Although violence has been
      traditionally approached from the perspectives of law and order, the tools of
      public health may also be used to contribute to solving this problem. Public
      health proposes a four step approach to prevent health problems: (1) defining the
      problem, (2) identifying its causes, (3) developing and evaluating interventions,
      and (4) disseminating effective interventions for wide-scale implementation. This
      paper describes how these methods were used to approach this problem in the city
      of Medellin.

PMID- 14658366
TI  - [What is evidence-based public health?].
AB  - Evidence based Public Health is the execution and evaluation of the efficiency of
      interventions, plans, programs, projects and politics in public health through
      the application of the scientific principles of reasoning, including the
      systematic use of information and information systems. Evidence based public
      health involves the use of methodologies similar to those applied in evidence
      based clinical medicine, but differs in its contents. In public health two types
      of evidence are described. The type I evidence in which a strong relation exists
      between the preventable risk and disease, and type II evidence in which there
      exists a relative effectivity of the public health interventions. In evidence
      based Public Health research designs more appropriate for the social sciences are
      used, as the observational and quasi-experimental studies. Likewise the decisions
      are more of interdisciplinary teams.

PMID- 14658367
TI  - [Opportunity, satisfaction, and reasons for not using health care services in
      Colombia, according to the Quality of Life Survey of the DANE, 1997].
AB  - OBJECTIVES: To identify, from a user's perspective, the satisfaction and
      opportunity of the health care services in Colombia and the reasons for not using
      them, in order to determine the achievements in health care quality since the
      promulgation of Law 100 of 1993. METHODS: The results of the home questionnaire
      of the National survey on Quality of Life carried out by the National
      Administrative Statistics department during the second semester of 1997, with a
      sub-sample of 10,016 homes, representing the country's population (39,824,424
      inhabitants), were analyzed. Only the variables pertinent to the research purpose
      were used, assigning new codes for them in order to allow performing the planned
      analyses. RESULTS: Opportunity and quality of the health care services were well
      evaluated by a part of the Colombian population. Some of the factors which
      determine variations in the evaluations of quality and opportunity, as well as
      the reasons for not using the health cares services, were determined. 64.7% of
      the people not using the health care services mentioned reasons associated with
      quality problems. Amongst the most important, were those related to
      accessibility: long distance to the health care provider, lack of money and lack
      of credibility in the health agents. CONCLUSIONS: The problems in the quality of
      the Social Security Services are greater than is usually considered. On the other
      hand, factors associated with the opportunity, quality (satisfaction) and reasons
      for not using health care services were identified.

PMID- 14658368
TI  - [Evaluation of effects of the health subsidy focalization policy on the
      population lacking payment capacity from our localities in Bogota, D.C.,
      Colombia, 2001].
AB  - OBJECTIVES: To analyze the problems of the focalization policy and the
      characteristics of decision-making to assign health subsidies for the population
      of Sisben levels 3 and 4 of 4 localities in Bogota, in order to propose criteria
      for transforming the processes of policy formulation and correct its defects on
      marginalization and exclusion. METHODS: A critical, participative and pluralist
      methodological approach, which combined multiple research methods and techniques
      from a systemic and post-estructuralist perspective, was undertaken. For sub
      projects were carried out. The subsidy-focalization policy in Colombia was
      analyzed based upon the arguments of the main socio-political actors who
      participated in its formulation. In order to establish how the focalization
      policy of health spending is perceived by the excluded population, the public
      providers and the local authorities, a qualitative study was done based upon
      focal groups and in-depth interviews. A follow-up of the accessibility to and use
      of health services was also carried out from the definition of a tracing
      condition. Finally, collective recommendations of policies were formulated from
      the per

PMID- 14658369
TI  - [Frequency of E. vermicularis in a rural school population of Quipile, Colombia,
      2001].
AB  - OBJECTIVES: To study the prevalence of Enterobius vermicularis infection in
      children aged 3 to 14 years in a rural zone of the town of Quipile, Colombia.
      METHODS: 159 children from 14 villages, with a homogeneous distribution according
      to their degree of scholarity, were studied. The detection of Enterobius
      vermicularis eggs was done by the Graham method. The design was a cross-sectional
      descriptive study, for which a convenience non-probabilistic sampling was carried
      out. Fisher's exact test and chi 2 were performed for data analysis. Multivariate
      analysis by multiple correspondence was also carried out. RESULTS: 2.5% of the
      children were found to be infected with E. vermicularis and 5% with Ascaris
      lumbricoides. This frequency is low when compared to reports from other authors;
      one of the possible causes is the sampling method used. CONCLUSIONS: Deficient
      sanitation conditions of the population studied as well as the low frequency of
      anal hygiene practices may represent behavioural risk factors which favour the
      transmission of this helminth.

PMID- 14658370
TI  - The RowPerfect ergometer: a training aid for on-water single scull rowing.
AB  - The purpose of this study was to compare rowing technique on the dynamic
      RowPerfect ergometer with a single scull. Eight national-level rowers performed
      on both the RowPerfect ergometer and in a single scull over 500 m, at rates of
      24, 26, and 28 strokes/minute. Blade force and oar angle (on-water) and handle
      force and stroke length (on the ergometer) were measured. Both force and stroke
      angle/length were normalised from 0 to 100 (where 100 was the peak value). Body
      positions of the subjects at both the catch and finish of each of these rowing
      strokes were also compared for each stroke rate. The coefficient of multiple
      determination (CMD) was used to measure the consistency of force curves over a
      sample of five sequential strokes for each rower. Cross-correlations were
      performed between the left- and right-side on-water sculling force curves and a
      mean of these values with the ergometer curve for each rower. Stroke
      angle/length, which did not vary with rate, was similar for both forms of rowing.
      The CMDs showed a high consistency across the normalised strokes of each subject
      (approximately 0.98). Cross-correlation values of 0.91, 0.92, and 0.93 were
      recorded between the force curves from the ergometer and on-water trials for
      stroke rates of 24, 26, and 28 strokes/minute, respectively. The mean trunk,
      thigh and lower leg angles at the catch and finish of the stroke were also
      similar across the stroke rates as determined by t-tests. Results indicate that
      technique used on the RowPerfect ergometer was similar to that for on-water
      sculling, thus validating its use in off-water training.

PMID- 14658371
TI  - Effects of the rider on the linear kinematics of jumping horses.
AB  - This study examined the effects of the rider on the linear projectile kinematics
      of show-jumping horses. SVHS video recordings (50 Hz) of eight horses jumping a
      vertical fence 1 m high were used for the study. Horses jumped the fence under
      two conditions: loose (no rider or tack) and ridden. Recordings were digitised
      using Peak Motus. After digitising the sequences, each rider's digitised data
      were removed from the ridden horse data so that three conditions were examined:
      loose, ridden (including the rider's data) and riderless (rider's data removed).
      Repeated measures ANOVA revealed significant differences between ridden and loose
      conditions for CG height at take-off (p < 0.001), CG distance to the fence at
      take-off (p = 0.001), maximum CG during the suspension phase (p < 0.001), CG
      position over the centre of the fence (p < 0.001), CG height at landing (p <
      0.001), and vertical velocity at take-off (p < 0.001). The results indicated that
      the rider's effect on jumping horses was primarily due to behavioural changes in
      the horses motion (resulting from the rider's instruction), rather than inertial
      effects (due to the positioning of the rider on the horse). These findings have
      implications for the coaching of riders and horses.

PMID- 14658372
TI  - Estimation of leg power: a two-variable model.
AB  - Leg power is an essential component for success in sports and athletic
      performance. Therefore, the leg power measurement may help athletes, coaches,
      athletic trainers, and rehabilitation specialists in selecting, treating, and
      training athletes for a specific sport. Using a conventional 'jump and reach'
      test, one can accurately predict the leg power and success in anaerobic-type
      sports. Nineteen untrained male subjects performed 'jump and reach' vertical
      jumps on a force platform. Power values were calculated from the force versus
      time data obtained from the force platform. A regression equation was obtained to
      predict the power values using the weight of an individual and the 'jump and
      reach' height as independent variables. The regression equation is given by p = 
      666.3 + 14.74 [Mass (kg)] + 1925.72 [Height (m)]; [R-square = 0.69, p < 0.05].

PMID- 14658373
TI  - Interaction of wrestling shoe and competition surface: effects on coefficient of
      friction with implications for injury.
AB  - The purpose of this study was to determine whether there is a significant
      difference in the co-efficient of friction (Fc) between old versus new wrestling
      shoes and mats and to investigate the effect of perspiration. Fc was measured by
      dragging a weighted shoe over a wrestling mat surface and measuring the vertical
      and horizontal forces produced. Three different shoe conditions were assessed
      over two mat types for both wet and dry conditions for a total of 12 conditions.
      To simulate the wet condition, saline solution was smeared over the surface of
      the mat. There was a significant effect of shoe, mat, and wet/dry conditions. In
      addition, significant interactions of shoe by mat, shoe by dry/wet, and mat by
      dry/wet were observed. Overall, Fc was 36% higher for the new wrestling mat
      compared to the old wrestling mat. Application of the saline solution reduced Fc
      by 14% compared to the dry condition. Comparison of the mean Fc for all three
      shoe types revealed the Fc for the older design shoe was 23% to 28% lower than
      the brand new shoe and the worn newer design, respectively. A high Fc, such as in
      the new mat/new shoe combination, has the potential to increase the risk of knee
      and ankle injuries by fixing the foot more securely to the ground.

PMID- 14658374
TI  - Primary factors affecting maximum torsional loading of the tibia in running.
AB  - The purpose of this study was to determine primary factors that contribute to the
      magnitude of the maximum torsional moment on the tibia during running based on
      information from three-dimensional shank kinematics and ground reaction forces.
      Eight male subjects were asked to run along a straight track at 5.0 m s-1. Data
      were collected using two high-speed cameras and a force platform. Each subject's
      left foot and tibia were modelled as a system of coupled rigid bodies. First, net
      axial moments acting at both ends of the tibia were calculated using inverse
      dynamics. Then the tibial torsional moment was determined from the quasi
      equilibrium balance of the net tibial axial moments. Our results showed
      considerable inter-individual variations for the tibial torsional moment during
      the stance phase of running. The maximum torsional moment reflecting external
      rotational loading of the proximal tibia was significantly correlated with the
      outward tilt angle of the shank in the frontal plane (r = 0.78, p < 0.05) and
      with the vertical force of ground reaction (r = 0.70, p < 0.05). In conclusion,
      lowering tibial torsional loading by interventions based on the present findings
      may lead to the reduction of running injuries that occur in athletes' tibiae.

PMID- 14658375
TI  - Effect of type 3 (oversize) tennis ball on serve performance and upper extremity
      muscle activity.
AB  - This study investigated the effect of the larger diameter (Type 3) tennis ball on
      performance and muscle activation in the serve. Sixteen male advanced tennis
      players performed serves using regular size and Type 3 tennis balls. Ball speed,
      surface electromyography, and serve accuracy were measured. There were no
      significant differences in mean initial serve speeds between balls, but accuracy
      was significantly greater (19.3%) with the Type 3 ball than with the regular
      ball. A consistent temporal sequence of muscle activation and significant
      differences in mean activation of different muscles were observed. However, ball
      type had no effect on mean arm muscle activation. These data, combined with a
      previous study, suggest that play with the larger ball is not likely to increase
      the risk of overuse injury, but serving accuracy may increase compared to play
      with the regular ball.

PMID- 14658376
TI  - Technique and timing in the women's reverse two and one half somersault tuck
      (305C) and the men's reverse two and one half somersault pike (305B) 3m
      springboard dives.
AB  - The purpose of this study was to compare the reverse two and one half somersault
      dive in a tuck position (305C) performed by females (n = 24), and the reverse two
      and one half somersault dive in a pike position (305B) performed by males (n =
      21), to determine changes required by females to successfully perform 305B. Key
      performance variables in reverse dives were also compared to those of forward
      dives. Video data of the dives performed at the 1999 FINA World Diving Cup were
      captured and digitised to obtain times and postures of the divers at specific
      events including hurdle landing, takeoff, and entry. Estimates of hurdle flight
      height and mass-normalised work done on the springboard were obtained from hurdle
      and flight times. The males did more work on the springboard to achieve greater
      height and rotation than females. Females performing 305C had less hip and knee
      flexion at hurdle landing than males performing 305B and took longer to achieve
      maximum hip flexion after takeoff from the springboard. To progress from 305C to
      305B females need to adjust their techniques to put more energy into the system.
      Desirable changes include increased height in the hurdle and increased hip and
      knee flexion prior to hurdle landing. Comparison of results for reverse dives
      with data previously presented for forward dives indicated that divers are more
      limited in the number of somersaults and dive position in reverse dives than
      forward dives despite equivalent or better height in reverse dives than forward
      dives.

PMID- 14658377
TI  - Kinematic and kinetic comparisons between American and Korean professional
      baseball pitchers.
AB  - The purpose of this study was to quantify and compare kinematic, temporal, and
      kinetic characteristics of American and Korean professional pitchers in order to
      investigate differences in pitching mechanics, performance, and injury risks
      among two different cultures and populations of baseball pitchers. Eleven
      American and eight Korean healthy professional baseball pitchers threw multiple
      fastball pitches off an indoor throwing mound positioned at regulation distance
      from home plate. A Motion Analysis three-dimensional automatic digitizing system
      was used to collect 200 Hz video data from four electronically synchronized
      cameras. Twenty kinematic, six temporal, and 11 kinetic variables were analyzed
      at lead foot contact, during the arm cocking and arm acceleration phases, at ball
      release, and during the arm deceleration phase. A radar gun was used to quantify
      ball velocity. At lead foot contact, the American pitchers had significantly
      greater horizontal abduction of the throwing shoulder, while Korean pitchers
      exhibited significantly greater abduction and external rotation of the throwing
      shoulder. During arm cocking, the American pitchers displayed significantly
      greater maximum shoulder external rotation and maximum pelvis angular velocity.
      At the instant of ball release, the American pitchers had significantly greater
      forward trunk tilt and ball velocity and significantly less knee flexion, which
      help explain why the American pitchers had 10% greater ball velocity compared to
      the Korean pitchers. The American pitchers had significantly greater maximum
      shoulder internal rotation torque and maximum elbow varus torque during arm
      cocking, significantly greater elbow flexion torque during arm acceleration, and
      significantly greater shoulder and elbow proximal forces during arm deceleration.
      While greater shoulder and elbow forces and torques generated in the American
      pitchers helped generate greater ball velocity for the American group, these
      greater kinetics may predispose this group to a higher risk of shoulder and elbow
      injuries.

PMID- 14658378
TI  - A new technique for assessing ball speed and impact force in volleyball.
AB  - This paper presents a description of a simple ballistic pendulum used for
      assessing ball speed and forces in volleyball. A seven-meter long pendulum with a
      wooden block of mass 10 kg was constructed and then used in conjunction with a
      specially designed timer with a precision of 10(-3)s to measure ball speed,
      pendulum speed and forces exerted to the ball and to the hand. Twelve volleyball
      players, ranging in ability from beginners to elite (National team) level were
      used as subjects, and separated into three groups; beginners, university and
      elite. All subjects performed five services of each kind. Subjects were
      instructed to jump to the height where the ball and pendulum were hung and hit it
      against the pendulum as hard as possible. A video camera, Panasonic M9000, was
      also used for the deviation angle measurement of pendulum. The results showed
      that highly skilled players receive larger forces and produce higher ball speeds
      than lower-level athletes.

PMID- 14658379
TI  - Do Golgi tendon organs really inhibit muscle activity at high force levels to
      save muscles from injury, and adapt with strength training?
AB  - Introductory textbooks commonly state that Golgi tendon organs (GTOs) are
      responsible for a reflex response that inhibits a muscle producing dangerously
      high tension (autogenic inhibition). Review of the relevant data from animal
      studies demonstrates that there is wide variability in the magnitude of, and even
      the presence of, GTO autogenic effects among locomotor hindlimb muscles, and that
      data on GTO effects under conditions of voluntary maximal muscle activation are
      lacking. A single available study on GTO function in humans, during a moderate
      contraction, surprisingly shows a reduction in autogenic inhibition during muscle
      force production. Further, it is not possible to find experimental evidence
      supporting the idea that strength training may produce a decrease in GTO mediated
      autogenic inhibition, allowing greater muscle activation levels and hence greater
      force production.

PMID- 14658380
TI  - Purine and pyrimidine nucleotide metabolism in higher plants.
AB  - Purine and pyrimidine nucleotides participate in many biochemical processes in
      plants. They are building blocks for nucleic acid synthesis, an energy source,
      precursors for the synthesis of primary products, such as sucrose,
      polysaccharides, phospholipids, as well as secondary products. Therefore,
      biosynthesis and metabolism of nucleotides are of fundamental importance in the
      growth and development of plants. Nucleotides are synthesized both from amino
      acids and other small molecules via de novo pathways, and from preformed
      nucleobases and nucleosides by salvage pathways. In this article the
      biosynthesis, interconversion and degradation of purine and pyrimidine
      nucleotides in higher plants are reviewed. This description is followed by an
      examination of physiological aspects of nucleotide metabolism in various areas of
      growth and organized development in plants, including embryo maturation and
      germination, in vitro organogenesis, storage organ development and sprouting,
      leaf senescence, and cultured plant cells. The effects of environmental factors
      on nucleotide metabolism are also described. This review ends with a brief
      discussion of molecular studies on nucleotide synthesis and metabolism.

PMID- 14658381
TI  - Aluminium differentially modifies lipid metabolism from the phosphoinositide
      pathway in Coffea arabica cells.
AB  - The effect of aluminium (Al) on phosphoinositide-specific phospholipase C (PLC)
      and lipid kinase activities was examined in a cellular suspension of coffee. Two
      main effects were seen when cells were treated with AlCl3. In periods as short as
      1 minute, Al-exposed cells increased the activity of PLC and IP3 formation up to
      two fold. Over longer periods PLC activity was inhibited by more than 50%. The
      activity of phosphatidylinositol 4-kinase (Pl 4-K), phosphatidylinositol
      phosphate 5-kinase (PIP 5-K) and diacylglycerol kinase increased when cells were
      incubated in the presence of different concentrations of AlCl3. The present study
      reports for the first time that Al may have different effects on the Pl-signaling
      pathway depending on the time of exposure. Our results strongly support the
      hypothesis that Al disrupts the metabolism of membrane phospholipids regulating
      not only PLC but also other enzymes that have key roles in signal-transduction
      pathways.

PMID- 14658382
TI  - Transgenic tobacco plants overexpressing cotton glutathione S-transferase (GST)
      show enhanced resistance to methyl viologen.
AB  - A GST (EC 2.5.1.18) gene (Gst-cr 1) from cotton was introduced into Nicotiana
      tabacum by Agrobacterium tumefaciens-mediated transformation. Transgenic tobacco
      plants overexpressing Gst-cr1 were normal in growth and mature compared with
      control, but had much higher levels of GST and GPx activities and showed an
      enhanced resistance to oxidative stress induced by a low concentration of methyl
      viologen (MV). Six antioxidant enzymes, glutathione S-transferase, glutathione
      peroxidase (EC 1.11.1.9), superoxide dismutase (EC 1.15.1.1), peroxidase (EC
      1.11.1.7), catalase (EC 1.11.1.6), and ascorbate peroxidase (EC 1.11.1.11) were
      monitored in transgenic lines and non-transgenic control during MV treatments.
      When they were treated with 0.03 mmol/L of MV, both transgenic lines and control
      showed a rapid increase in the activities of GST, GPx, SOD, POD, APx, while the
      activity of CAT seemed to be irregular. The percent of the increase in SOD and
      POD activities was much higher in control than in transgenic plants. When treated
      with 0.05 mmol/L of MV, both control and transgenic plants were severely damaged,
      and the activities of the six enzymes decreased sharply.

PMID- 14658383
TI  - Malate and malate-channel antibodies inhibit electrogenic and ATP-dependent
      citrate transport across the tonoplast of citrus juice cells.
AB  - Citrus juice cells accumulate high levels of citric acid in their vacuoles when
      compared to other organic ions including malate. Uptake of citrate into tonoplast
      vesicles from Citrus juice cells was investigated in the presence of malate, and
      after incubation with antibodies raised against the vacuolar malate-specific
      channel of Kalanchoe diagremontiana leaves. Antibodies against the vacuolar
      malate channel immunoreacted with a protein of similar size in tonoplast extracts
      from three Citrus varieties differing in citric acid content. Malate channel
      antibodies inhibited both delta MicroH(+)-dependent and delta MicroH(+)
      independent ATP-dependent citrate transport, indicating common domains in both
      transport systems and to the malate-specific channel of Kalanchoe diagremontiana
      leaves. Malate strongly inhibited electrogenic citrate transport, whereas ATP
      dependent citrate uptake was less affected. Kinetic analysis of citrate transport
      in the presence of malate confirmed the existence of two citrate transport
      mechanisms and indicated that both citrate and malate share a common transport
      channel across the tonoplast of Citrus juice cells.

PMID- 14658384
TI  - Bundle sheath chloroplasts of rice are more sensitive to drought stress than
      mesophyll chloroplasts.
AB  - We investigated the effects of drought stress on the ultrastructure of
      chloroplasts in rice plants. After the seedlings were grown in a glasshouse for 1
      month, they were treated for drought stress using two methods. One drought
      treatment was imposed by reducing the water supply to the plants for 1 month. The
      other was imposed by withholding water for 2 weeks to examine the withering
      process of leaves by drought stress. The ultrastructural changes of chloroplasts
      in bundle sheath cells were more prominent than those in mesophyll cells under
      both drought stress treatments. Ribulose-1,5-bisphosphate carboxylase/oxygenase
      (rubisco) content in bundle sheath chloroplasts reduced more dramatically than in
      mesophyll chloroplasts by drought stress. Although a slight swelling of
      thylakoids was sometimes observed in bundle sheath chloroplasts in moderate
      stress for 1 month, the thylakoids were less affected by drought stress than
      chloroplast envelope. These results suggest that chloroplasts in bundle sheath
      cells were more sensitive to drought stress than those in mesophyll cells and the
      thylakoids were less damaged by drought stress compared with chloroplast
      envelope.

PMID- 14658385
TI  - No photoperiodoc control of the formation of turions in eight clones of Spirodela
      polyrhiza.
AB  - The influence of daily photoperiod (8, 16, 24 h) on eight clones of Spirodela
      polyrhiza was tested in two different nutrient media. The number of vegetative
      fronds and resting turions formed after 50 days of cultivation were scored. The
      specific turion yield (STY; number of turions formed per vegetative frond) was
      used to evaluate the effectiveness of turion formation of the tested clones. All
      clones formed turions in both nutrient media. The STY varied substantially
      between the different clones, ranging from 0.22 +/- 0.03 (clone SC from Cuba) to
      3.9 +/- 0.3 (clone 9256 from Finland) in continuous light. The STY increased with
      increasing duration of the photoperiod. This increase may have been due to the
      extended period of photosynthesis rather than that of a photoperiodic long-day
      response. Shorter photoperiods did not stimulate turion formation in any of the
      clones. S. polyrhiza is a day-neutral plant with respect to turion formation, as
      noted previously (Appenroth et al. 1990. Annals of Botany 66: 163-168). In
      accordance with this conclusion, no correlation was detected between the STY and
      the latitude at which the clones occur naturally. Environmental factors other
      than shortening of photoperiods seem to be effective in signalling seasonal
      changes of growth conditions in advance to S. polyrhiza.

PMID- 14658386
TI  - Ethylene advances the transition from vegetative growth to flowering in
      Arabidopsis thaliana.
AB  - The transition from vegetative growth to flowering is the most drastic change in
      plant development. In order to examine the involvement of ethylene in growth
      transition, we compared the development of ethylene-related mutants, eto1, etr1,
      ein2-1 and ein3-1, with the wild type (WT) in Arabidopsis thaliana. The ethylene
      sensitivity of two WT and the mutants is decreased in the following order: eto1 =
      WT < ein3-1 < ein2-1 = etr1-1. Bolting time was also delayed in nearly the same
      order: eto1 < WT < ein3-1 < ein2-1 < etr1. Leaf numbers increased according to
      the delay of bolting time, indicating that the delay of bolting time was caused
      by the delay of transition from vegetative to reproductive growth. Other growth
      parameters, including leaf area and number of flowers opening at the same time,
      increased in the same order, indicating that these changes were caused by a
      single factor, the amount of ethylene signal which was transferred though an
      ethylene signal transduction pathway. These results suggest that ethylene is
      involved in the transition from vegetative to reproductive growth in Arabidopsis
      thaliana.

PMID- 14658387
TI  - Effect of hypobaric conditions on ethylene evolution and growth of lettuce and
      wheat.
AB  - Elevated levels of ethylene occur in enclosed crop production systems and in
      spaceflight environments, leading to adverse plant growth and sterility. There
      are engineering advantages in growing plants at hypobaric (reduced atmospheric
      pressure) conditions in biomass production for extraterrestrial base or
      spaceflight environments. Objectives of this research were to characterize the
      influence of hypobaria on growth and ethylene evolution of lettuce (Lactuca
      sativa) and wheat (Triticum aestivum). Plants were grown under variable total gas
      pressures [from 30 to 101 kPa (ambient)]. In one study, lettuce and wheat were
      direct seeded, germinated and grown in the same chambers for 28 d at 50 or 101
      kPa. Hypobaria increased plant growth and did not alter germination rate. During
      a 10-day study, 28-day-old lettuce and 40-day-old wheat seedlings were
      transplanted together in the same low and ambient pressure chambers; ethylene
      accumulated in the chambers, but the rate of production by both lettuce and wheat
      was reduced more than 65% under 30 kPa compared with ambient pressure (101 kPa).
      Low O2 concentrations [partial pressure of O2 (pO2) = 6.2 kPa] inhibited ethylene
      production by lettuce under both low (30 kPa) and ambient pressure, whereas
      ethylene production by wheat was inhibited at low pressure but not low O2
      concentration. There was a negative linear correlation between increasing
      ethylene concentration and decreasing chlorophyll content of lettuce and wheat.
      Lettuce had higher production of ethylene and showed greater sensitivity to
      ethylene than wheat. The hypobaric effect on reduced ethylene production was
      greater than that of just hypoxia (low oxygen).

PMID- 14658388
TI  - Evidence for recycling of inorganic phosphate by wheat chloroplasts during
      photosynthesis at air levels of CO2 and O2.
AB  - Phosphate recycling under photorespiratory conditions was investigated using
      intact wheat chloroplasts from Triticum aestivum (cv. Maris dove). A decline in
      the optimal Pi level needed to support steady-state photosynthesis was observed
      (a) as the bicarbonate supply became limiting, or (b) as oxygen concentrations
      were increased. Further, at subsaturating CO2 and elevated O2 (52%),
      photosynthetic induction periods were shortest in the absence of exogenous Pi,
      and severely extended by its addition. Thus, photosynthesis under low CO2 levels
      which favor ribulose 1,5 bisphosphate (RuBP) oxygenase activity and glycolate
      synthesis by chloroplasts decreases their dependency on exogenous Pi from the
      initial illumination of chloroplasts through to the attainment of steady state
      rates of O2 evolution. Uptake of phosphate (Pi) was directly measured at ambient
      O2 concentrations and showed the stoichiometry of O2 evolved to Pi consumed at 10
      mmol/L bicarbonate (saturating) had a mean value of 3.0, and was increased to 5.4
      at 2.5 mmol/L bicarbonate and to > 8.0 at 1.0 mmol/L bicarbonate. The observation
      is consistent with enhanced stromal recycling of Pi released during hydrolysis of
      phosphoglycolate produced in greater quantities as the ratio of RuBP carboxylase
      relative to oxygenase activities (vc/vo) declines. The theoretical relationship
      between vc/vo and O2/Pi stoichiometries was derived and compared favorably to
      experimental data obtained.

PMID- 14658389
TI  - Ion allocation in two different salt-tolerant Mediterranean Medicago species.
AB  - The relationship between Na+, major cation concentrations and salt tolerance
      under long-term saline conditions of Medicago arborea and Medicago citrina was
      studied. Plants were grown in solution culture in 1, 50, 100, or 200 mmol/L NaCl
      for 30 days in a climate-controlled greenhouse. Stem and petiole growth was the
      most affected by salt in both species. Leaf growth was inhibited in M. arborea,
      with increased salt, while only the 200 mmol/L NaCl-treated M. citrina plants
      were significantly affected. Both species had the highest Na+ concentrations in
      the shoots, however, the allocation pattern was different; M. arborea showed the
      highest concentrations in the leaf blades, whereas M. citrina distributed the
      salt into the petioles. K+/Na+ ratio decreased with salt in both species;
      however, leaf K+ use efficiency (g leaf DW mg-1 leaf K+) was higher in M.
      citrina. The difference in Na+ allocation and cation concentrations found in
      these medic species and their importance is discussed in relation to their
      response to NaCl salinity.

PMID- 14658390
TI  - Functional analysis of a beta-1,3-glucanase gene (Tag1) with anther-specific RNA
      and protein accumulation using antisense RNA inhibition.
AB  - A critical stage in pollen development is the dissolution of tetrads into free
      microspores. Tetrads are surrounded by a wall composed primarily of beta-1,3
      glucan. At the completion of meiosis, tetrads are released into the anther locule
      after hydrolysis of the callose by a beta-1,3-glucanase complex. The cDNA
      corresponding to a beta-1,3-glucanase cloned from tobacco (Tag 1) represents a
      gene that is highly similar to other beta-1,3-glucanases and is expressed
      exclusively in anthers from the tetrad to free microspore stage of pollen
      development. Tag 1 protein was overexpressed in E. coli, accumulating in
      insoluble inclusion bodies. Polyclonal antibodies against Tag 1 recombinant
      protein identify a single 33 kD protein accumulating only in anthers at tetrad
      and free microspore stages where beta-1,3-glucanase activity is present.
      Transgenic plants expressing Tag 1 antisense RNA were produced. Although Tag 1
      RNA and protein levels were greatly reduced, tetrad dissolution and pollen
      development were normal. These data indicate that under the conditions these
      tobacco plants were grown, wild type levels of Tag 1 protein are not necessary
      for male fertility.

PMID- 14658391
TI  - Temperature-regulated expression of a glycine-rich RNA-binding protein in the
      halotolerant alga Dunaliella salina.
AB  - Acclimation of the halotolerant alga Dunaliella salina to low temperature induced
      the accumulation of a 12.4 kDa protein (DsGRP-1) and reduction of a 13.1 kDa
      protein (DsGRP-2). DsGRP-1 and DsGRP-2 are boiling-stable proteins that are
      localised in the cytoplasm, as revealed by sub-cellular fractionation and by
      immuno-localisation. The proteins were partially purified and their corresponding
      genes were cloned. The predicted sequences are homologous to Glycine-Rich RNA
      binding Proteins (GRPs) from plants and cyanobacteria. The nucleotide sequences
      of grp1 and grp2 differ in a short insert encoding 9 amino acids in the glycine
      rich domain of DsGRP-2. grp2 contains a single intron at position 179 indicating
      that DsGRP-1 and DsGRP-2 are not derived from alternative splicing of a common
      gene. The level of grp mRNA increased at 7 degrees C and was rapidly depressed at
      24 degrees C. Analysis of binding to ribonucleotide homopolymers revealed that
      DsGRP-1 and DsGRP-2 bind preferentially to poly-G and to poly-U indicating that
      they are RNA-binding proteins. It is proposed that DsGRP-1 and DsGRP-2 are
      encoded by distinct genes which are differentially regulated by temperature.

PMID- 14658392
TI  - Isolation and characterisation of a sucrose: sucrose 1-fructosyltransferase gene
      from perennial ryegrass (Lolium perenne).
AB  - A sucrose: sucrose 1-fructosyltransferase (1-SST) gene and cDNA (Lp 1-SST) from
      perennial ryegrass (Lolium perenne) were isolated. The Lp 1-SST gene was fully
      sequenced and shown to contain three exons and two introns. Nucleotide sequence
      analysis of the 4824 bp Lp 1-SST genomic sequence revealed 1618 bp of 5' UTR and
      an open reading frame of 1962 bp encoding a protein of 653 amino acids. Lp 1-SST
      is 95% identical to the tall fescue 1-SST and contains plant fructosyltransferase
      functional domains. Lp 1-SST corresponds to a single copy gene in perennial
      ryegrass, and is expressed in young leaf bases and mature leaf sheaths. The
      recombinant Lp 1-SST protein from corresponding cDNA expression in Pichia
      pastoris showed 1-SST activity.

PMID- 14658393
TI  - Characterization of Plasmopara-resistance in grapevine using in vitro plants.
AB  - Although the exact mechanisms by which grapevine cells operate to reduce disease
      incidence caused by the downy mildew fungus Plasmopara viticola are not fully
      elucidated, our cytological results obtained from infected in vitro-plants
      confirm that enhanced disease resistance is associated with an expression of
      distinct reactions in a chronological order. An increased production of reactive
      oxygen species (superoxide radicals, 4-6 hours post infection, hpi) was followed
      by a hypersensitive response (6-8 hpi), an increased activity of peroxidase in
      cells flanking the infection area and in the vascular tissue (10-12 hpi) and an
      increased production, accumulation or conversion of phenolic compounds (12-15
      hpi). These mechanisms seem also to be present in susceptible varieties as shown
      after an inoculation with non-host oomycetic pathogens on the basis of peroxidase
      activity, but they do not become activated after P. viticola infection. The
      investigation of the peroxidase activity in leaves at several time points after
      an infection with P. viticola indicated that there is a strong correlation
      between the POX activity in leaves of in vitro-plants and the resistance of
      grapevine plants to P. viticola in the field.

PMID- 14658394
TI  - Isoenzymes of peroxidase and esterase related to morphogenesis in Mammillaria
      gracillis Pfeiff. tissue culture.
AB  - In vitro propagated plants of the cactus Mammillaria gracillis Pfeiff.
      (Cactaceae) spontaneously produced callus. The habituated callus regenerated
      normal and hyperhydric shoots without the addition of grown regulators. Tumours
      were obtained by infecting cactus explants with Agrobacterium tumefaciens; the
      wild strain B6S3 (tumour TW) or with the rooty mutant GV3101 (tumour TR). Both
      tumour lines grew vigorously, never expressing any morphogenic potential. In this
      study, cactus shoots, callus, normal and hyperhydric regenerants and TW and TR
      tumours were compared with regard to peroxidase (EC 1.11.1.7) and esterase
      activity, and isoenzyme patterns. Guaiacol peroxidase activity was the lowest in
      the cactus shoots and in the normal regenerants. Callus, hyperhydric regenerants
      and tumours had peroxidase activity of 6 to 7 times higher. Esterase activity was
      measured with 1- and 2-naphthylacetate as broad-spectrum substrates. The highest
      esterase activity was determined in tumours with both substrates. All tissues,
      except the TR tumour, had higher esterase activity for 2-compared to 1
      naphtylacetate. Peroxidase and esterase isoenzyme patterns were not completely
      identical among the investigated tissues.

PMID- 14658395
TI  - Alterations in endogenous levels of cytokinins following grafting of Pinus
      radiata support ratio of cytokinins as an index of ageing and vigour.
AB  - Markers for ageing or maturation in woody plants provides the possibility of
      identifying genotypes with a prolonged juvenile phase, or to evaluate
      reinvigoration procedures, such as grafting of adult material. This study focuses
      specifically on cytokinins (Cks) as markers, due to their role in the transition
      process from juvenile to adult states. Previous reports from our group disclosed
      that the ratio of isopentenyladenine-type (iP-type) to zeatin-type (Z-type) Cks
      decreases during tree maturation, a maturation and ageing index being likely in
      Pinus radiata. Based on these results, Cks were tested in terminal buds of adult
      and grafted adult P. radiata material to corroborate the importance of the
      aforementioned balance as an index in the reinvigoration process of adult trees
      associated with grafting procedures. Results revealed the reversion of this index
      pattern parallel to the reactivation of some juvenile traits, namely, increasing
      values of the ratio throughout the reinvigoration process. According to previous
      results, however, the opposite was the case during the reverse process. This fact
      allowed us to validate the iP-type/Z-type Ck ratio as an ageing and vigour index.

PMID- 14658396
TI  - Xyloglucan breakdown during cotton fiber development.
AB  - Cotton (Gossypium herbaceum L.) fibers elongated almost linearly up to about 20
      days post anthesis. The molecular mass of xyloglucans in fiber cell walls
      decreased gradually during the elongation stage. When enzymatically active
      (native) cell wall preparations of fibers were autolyzed, the molecular mass of
      xyloglucans decreased. The decrease was most prominent in wall preparations
      obtained from the rapidly elongating fibers. The xyloglucan-degrading activity
      was recovered from the fiber cell walls with 3 mol/L NaCl, and the activity was
      high at the stages in which fibers elongated vigorously. These results suggest
      the possible involvement of xyloglucan metabolism in the regulation of cotton
      fiber elongation.

PMID- 14658397
TI  - [Cardiac sympathetic dysfunction in Parkinson's disease--relationship between
      results of 123I-MIBG scintigraphy and autonomic nervous function evaluated by the
      Valsalva maneuver].
AB  - We examined whether the results of 123I-MIBG scintigraphy reflect cardiac
      sympathetic nerve function in patients with Parkinson's disease (PD). The
      subjects were 62 patients with Parkinson's disease (age, 65.4 +/- 6.3 years) and
      53 controls (65.2 +/- 7.1 years). All subjects underwent 123I-MIBG scintigraphy
      and QTc interval measurement on ECG. Hemodynamic autonomic function was estimated
      by the Valsalva maneuver in 37 subjects (63.9 +/- 5.2 years) randomly selected
      from the patients with PD. As control, the Valsalva maneuver was also done in 20
      randomly selected controls (64.1 +/- 5.0 years), and 123I-MIBG scintigraphy was
      performed in 21 controls (67.7 +/- 5.3 years old). The subjects rested in a
      supine position for 20 min and were given an intravenous injection of 111 MBq
      123I-MIBG. Relative organ uptake was determined by the region of interest (ROI)
      in the anterior view and the ratio of average pixel count in the heart (H) to
      that in the mediastinum (M) was calculated (H/M ratio) for early (after 15 min)
      and delayed (after 3 hrs) periods. The Valsalva maneuver was done by having the
      subjects exhale into a mouthpiece at an expiratory pressure of 40 mmHg for 15
      seconds. Blood pressure and RR intervals were measured during the Valsalva
      maneuver by tonometry, using a noninvasive blood pressure monitoring system (ANS
      508, Nihon Colin Co., Ltd.). Baroreceptor reflex sensitivities (BRS) of the
      second phase (BRS II) and fourth phase (BRS IV) of the Valsalva maneuver were
      calculated, and blood pressure elevations during the late second phase (IIp) and
      fourth phase (IVp) were measured. QTc was greater in the patients with PD (417
      ms) than in the control subjects (409 ms). The H/M ratios of the early and
      delayed images in the patients with PD (1.76, 1.61) were significantly lower than
      those in the control subjects (2.56, 2.45). The early and delayed H/M ratios
      significantly correlated with the severity of disease according to Hoehn-Yahr
      stage. QTc interval and IVp significantly correlated with early and delayed H/M
      ratios. No other significant correlations were detected. The early H/M ratio in
      the patients with PD who had IVp within the normal range was lower than the early
      H/M ratio in control subjects. Our results show that early and delayed H/M ratio
      correlates with cardiac autonomic function, evaluated on the basis of QTc
      interval and the Valsalva maneuver, but not with baroreceptor reflex sensitivity
      or vasomotor autonomic function. Our findings suggest that silent cardiac
      autonomic dysfunction may be evaluated by 123I-MIBG scintigraphy, because early
      and delayed H/M ratios were lower in the patients with PD who had normal IVp than
      in the control subjects.

PMID- 14658398
TI  - [A young patient of acute encephalitis complicated with acyclovir encephalopathy
      without renal dysfunction].
AB  - A previously healthy 30-year-old woman was admitted to our hospital because of
      impaired consciousness after convulsion. A temporary diagnosis of herpes simplex
      encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times
      daily in normal saline over 2 hours) was started. Three days later, she became
      confused, and was having hallucinations, dysarthria and generalized painful
      seizures occurred without focal neurologic deficit. Whether the neuropsychiatric
      symptoms were related to herpes simplex encephalitis or acyclovir neurotoxity was
      initially unclear. The brain MRI and lumbar puncture findings were initially
      normal, but abnormal FLAIR lesions appeared later. ACV-associated encephalopathy
      was considered. ACV was discontinued, and she recovered from the neurological
      disorder within 24 hours. Although blood levels of acyclovir were not determined,
      it is unlikely that they were in a toxic range, in view of her normal renal
      function.

PMID- 14658399
TI  - [A patient with primary angiitis of the central nervous system: relation between
      MRI and pathological findings].
AB  - A 74-year-old woman, noticed sudden onset of quadriparesis when getting up in the
      morning on July 17th, 1992. At admission, she presented mild weakness of the
      limbs bilaterally, and deep tendon hyperreflexia, which were improved after about
      4 hours. Serum and urinary laboratory examinations revealed no abnormal findings.
      Cerebrospinal fluid showed increased cells (75/mm3), and protein (58 mg/dl).
      Computed tomography revealed multiple low density lesions in the frontal,
      parietal, and occipital cortex. Magnetic resonance imaging showed low signal
      intensities on T1-weighted images and high signal intensities on T2-weighted
      images, suggesting tumorous lesions. On the gadolinium-enhanced images, the
      enhanced lesions were surrounded with low signal intensity. She developed
      hallucination and disorientation since around the 8th hospital day, and
      disturbance of consciousness at the 15th day, followed by coma, and she died from
      respiratory failure on the 17th hospital day. At autopsy, there were multiple
      small infarctions in the cerebral cortex and dark areas in the meninges,
      suggesting localized inflammation. On microscopical examination, remarkable
      proliferation of cells was seen at the small arteries of the leptomeninges and
      cerebral cortex. Parts of the vessels were replaced by multinucleated giant
      cells. No similar abnormalities were found in arteries in the other organs,
      except the central nervous system. The pathological diagnosis of primary angiitis
      of the central nervous system was made based on the above findings. The enhanced
      MRI findings were in excellent agreement with the pathological leptomeningeal
      vasculitis. The surrounding low intensity areas on the enhanced MRI were
      considered to reveal edematous change and infarction in the parenchymal lesions.
      We conclude that enhanced MRI is useful to make a diagnosis of CNS vasculitis.

PMID- 14658400
TI  - [A case of acute cholinergic adverse effects induced by donepezil overdose: a
      follow-up of clinical course and plasma concentration of donepezil].
AB  - A 79-year-old woman with Alzheimer's disease was admitted due to acute
      cholinergic symptoms induced by overdose (45 mg) of donepezil (DPZ). Physical
      examination showed bradycardia, sinus arrhythmia, vomiting and respiratory
      insufficiency. She was treated with atropine intravenously and her cholinergic
      symptoms subsided in the next evening. After 5 days she was discharged from the
      hospital and DPZ was withholded for about 4 weeks. The plasma concentration of
      DPZ was 54.6 ng/ml on admission and gradually decreased to the normal limits in
      about 90 hours. The calculative half-life of DPZ was about 55 hours. Since the
      half-life of DPZ is long and differs between individuals, hospitalization and
      treatment with atropine is recommended for cholinergic side effects induced by
      overdose of DPZ. It is important to prevent dosing errors in cooperation with
      medical providers, patients and families.

PMID- 14658402
TI  - [Clinical features and neuropathological findings of familial amyotrophic lateral
      sclerosis with an H43R mutation in Cu/Zn superoxide dismutase].
AB  - We report the clinical and neuropathological features of a Japanese family with
      familial amyotrophic lateral sclerosis (FALS), whose members have an amino acid
      substitution of histidine by arginine in Cu/Zn superoxide dismutase. A 58-year
      old woman developed muscle weakness in the legs, and died of respiratory
      insufficiency 7 months after the onset of her weakness. Her family history
      included 7 patients with FALS over 3 generations. Their pertinent neurological
      abnormalities consisted primarily of lower motor neuron signs, and their clinical
      progression was rapid. Autopsy of our patient showed the involvement of the lower
      and upper motor neuron systems with Lewy body-like hyaline inclusions, in
      addition to degeneration in the posterior columns, Clarke's nuclei and posterior
      spinocerebellar tracts. The inclusions reacted with both anti-SOD1 and anti
      ubiquitin antibodies. This is the first report of the neuropathological findings
      of FALS with this mutation.

PMID- 14658401
TI  - [A case of alien hand syndrome after right posterior cerebral artery territory
      infarction].
AB  - We report a 63-year-old right-handed man who presented an alien hand syndrome
      (AHS). He complained of clumsiness of his left hand and admitted to our hospital.
      On the first examination, he presented left homonymous hemianopia, left spatial
      neglect and left limb ataxia, but neither paralysis nor sensory impairment. A few
      days after, he complained that his left hand was controlled by someone else, and
      we considered this phenomenon as AHS. At that time, he lost sensation of almost
      all modalities including deep sensation on his left upper and lower limb.
      Magnetic resonance image examination was performed, and it showed acute cerebral
      infarction at right posterior cerebral artery territory including right thalamus
      (ventral posterior lateral nucleus). Generally, AHS is caused by left
      mediofrontal and callosal lesion (frontal type AHS), or by callosal with
      bilateral frontal or without frontal lesion (callosal type AHS). However, some
      cases were reported that they presented AHS after damage of the basal ganglia,
      right thalamus, right occipital or inferior parietal lobe. Some authors described
      this phenomenon as "sensory" or "posterior" type AHS. In such cases, included our
      case, we speculate that sensory impairment causes AHS. Especially in our case,
      AHS might be caused by not only the sensory impairment but also by left
      homonymous hemianopia and left spatial neglect. So, because of these symptoms,
      our patient could not recognize the motion of the left hand, and presented AHS.
      We think that this "sensory" or "posterior" type AHS should be distinguished from
      frontal and callosal type AHS.

PMID- 14658403
TI  - [A patient with giant cell myocarditis and myositis associated with thymoma and
      myasthenia gravis].
AB  - We report a 62-year-old man with giant cell myocarditis and myositis associated
      with thymoma and myasthenia gravis (MG). He was diagnosed as having MG and
      invasive thymoma at the age of 45. After he had a myasthenic crisis at the age of
      61, tacrolimus was indicated in order to improve his neurological symptoms, in
      addition to glucocorticoid. Three months later, he was readmitted to our hospital
      complaining of general fatigue and dyspnea. Serum level of creatine phosphokinase
      (9,835IU/L) and myocardium-derived troponin T (3.24 ng/mL) were elevated, and the
      ECG showed atrioventricular dissociation and accelerated idioventricular rhythm.
      In spite of glucocorticoid pulse therapies and high-dose immunoglobulin
      therapies, he died of cardiac failure within a few days. Autopsy was done, and
      histological examination of the myocardium and the skeletal muscle showed massive
      necrosis with infiltration of inflammatory cells including giant cells. These
      findings constituted giant cell myocarditis and myositis. Although it has been
      suggested that myocardial disorders can often occur in patients with thymoma
      and/or MG, the mechanism involved is still unknown. This report may provide new
      knowledge about the pathophysiology of giant cell myocarditis and myositis
      associated with thymoma and MG.

PMID- 14658404
TI  - [Blepharospasm in a patient with thymoma and positive anti-acetylcholine receptor
      antibody].
AB  - We report a rare case of a 70-year-old woman diagnosed as having blepharospasm
      with positive anti-acetylcholine receptor antibody. Blepharospasm developed in
      November, 2000, and increased in frequency, and worsened toward the evening. She
      complained of difficulty in her eyelid opening from October, 2002. Neurological
      examinations revealed blepharospasm and mild ptosis in both eyes. Tensilon test
      was negative. Waning and waxing were not detected in bilateral orbicularis oculi
      muscles by Harvey-Masland test. However, anti-acetylcholine receptor antibody was
      positive and thymoma in the anterior mediastinum was also found by the computed
      tomography of the chest. After the thymectomy, frequency of blepharospasm
      decreased. When blepharospasm worsened toward the evening, the co-existence of
      myasthenia gravis should be borne in mind.

PMID- 14658405
TI  - [Successful early-stage corticosteroid treatment in a case of granulomatous
      angiitis of the central nervous system].
AB  - A 74-year-old woman presented with progressive mental deterioration following a
      low-grade fever and headache. Upon admission, she appeared lethargic, could not
      obey simple commands and was disoriented to time, place and person. She had low
      grade fever and mild neck stiffness. The cerebrospinal fluid had an elevated
      protein content of 496 mg/dl, contrast-enhanced MRI revealed diffuse
      leptomeningeal enhancement, particularly in the occipital area, and a cerebral
      angiogram showed diffuse segmental narrowing of multiple intracranial arteries,
      especially in the distal portion of the right middle cerebral artery. A clinical
      diagnosis of granulomatous angiitis of the central nervous systems (GANS) was
      made, and corticosteroid therapy was initiated. The patient improved gradually,
      and corticosteroid therapy was tapered to the maintenance dose (prednisolone 0.4
      mg/kg daily). An open brain biopsy showed multiple vessels containing
      granulomatous inflammation with giant cells. GANS is one of the most challenging
      neurologic disorders to diagnose because of its relative rarity and the lack of
      specificity of clinical signs and efficient, non-invasive, diagnostic tests. In
      this case, we were able to begin corticosteroid therapy in the early stage of the
      disease (before brain biopsy), and it yielded a good outcome.

PMID- 14658406
TI  - [Siblings with dysferlinopathy presenting different clinical course].

PMID- 14658407
TI  - Clinical significance of acute-phase brain natriuretic peptide in acute
      myocardial infarction treated with direct coronary angioplasty.
AB  - OBJECTIVES: To investigate the relationship between brain natriuretic peptide
      (BNP) plasma concentration levels and the clinical course, mortality and success
      of left ventricular remodeling by direct percutaneous coronary intervention (PCI)
      in patients with acute myocardial infarction. METHODS: One hundred thirty
      consecutive first-acute myocardial infarction patients were successfully
      reperfused by direct PCI. BNP plasma concentration levels were assessed at 24 hr
      from onset, and patients were divided into the high (> or = 290 pg/ml) plasma BNP
      group (H-BNP group; n = 65) or low (< 290 pg/ml) plasma BNP subset (L-BNP group;
      n = 65). Left ventriculography was performed in both the acute (following
      reperfusion therapy) and chronic (20 +/- 8 days after onset) stages to evaluate
      left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume
      index (LVEDVI) and regional wall motion (RWM). Differences between the parameters
      at the two stages (chronic stage--acute stage) were expressed as delta LVEF,
      delta LVEDVI, and delta RWM. RESULTS: There were significantly more major
      complications in the H-BNP group than in the L-BNP group. There was significantly
      higher mortality in the H-BNP group (p < 0.01). Multivariate analysis identified
      only BNP plasma concentration as an independent predictor of mortality (p <
      0.05). There were no significant differences in left ventricular function in the
      acute stage between the groups, but LVEF, LVEDVI, and RWM were all significantly
      worse in the chronic stage in the H-BNP group compared with the L-BNP group.
      Moreover, delta LVEF (p < 0.001), delta LVEDVI (p < 0.05), and delta RWM (p <
      0.01) were also significantly worse in the H-BNP group. CONCLUSIONS: Early-phase
      BNP plasma concentrations after successful PCI in patients with acute myocardial
      infarction may be correlated closely with major complications, and may be of
      prognostic importance. BNP plasma concentration may also be an indicator of left
      ventricular remodelling.

PMID- 14658408
TI  - Involvement of inflammation in acute coronary syndromes assessed by levels of
      high-sensitivity C-reactive protein, matrix metalloproteinase-9 and soluble
      vascular-cell adhesion molecule-1.
AB  - OBJECTIVES: Inflammation is important in the development of atherosclerosis.
      Matrix metalloproteinases (MMPs) and interferon-gamma which participate in
      collagen degradation are pathological factors in plaque vulnerability as an
      important mechanism underlying acute coronary syndrome. This study investigated
      whether inflammation is related to the onset of acute coronary syndrome. METHODS:
      This study included 56 patients with acute coronary syndrome (ACS group), 104
      patients with chronic coronary artery disease (S group), and 38 control subjects
      with no evidence of ischemic heart disease (C group). High-sensitivity C-reactive
      protein (hs-CRP), MMP-9, and interferon-gamma were measured in peripheral blood
      samples. Soluble adhesion molecules (VCAM-1, ICAM-1) were also measured as
      inflammatory markers. RESULTS: The hs-CRP level was significantly higher in the
      ACS group (44.5 mg/l) than in the S group (2.1 mg/l) and the C group (0.6 mg/l)
      (p < 0.0001). The MMP-9 level was also significantly higher in the ACS group
      (333.8 ng/ml) than in the S group (110.8 ng/ml) and the C group (72.0 ng/ml) (p <
      0.0001). The VCAM-1 level was significantly higher in the ACS group (506.5 ng/ml)
      than in the C group (448.8 ng/ml) (p < 0.05). The ICAM-1 level and the interferon
      gamma level did not differ between the groups. There was a significant positive
      correlation between the level of hs-CRP and the level of the collagen degradation
      product MMP-9 (r = 0.52) in all subjects. CONCLUSIONS: These results suggest that
      plaque destabilized by MMP-9 produced in response to inflammation participates in
      the mechanism of acute coronary syndrome.

PMID- 14658409
TI  - [Coronary risk factor management in primary practice in Shibuya, Tokyo].
AB  - OBJECTIVES: Many large-scale clinical trials have confirmed that coronary risk
      factors such as hypertension, hyperlipidemia and diabetes mellitus predict a
      higher incidence of cardiovascular events and that control of these risk factors
      reduces the incidence. However, the actual management of such risk factors and
      the resultant improvement of the cardiovascular events in primary practice
      remains unclear. The Heart Care Network Shibuya, a voluntary study group of
      regional primary physicians, surveyed the management of coronary risk factors and
      the clinical outcomes. METHODS: Behavioral patterns of the coronary risk factor
      was investigated in the management and resultant changes of the risk factors in
      209 outpatients (mean age 65.6 +/- 11.2 years) with more than one of
      hypertension, hyperlipidemia, diabetes mellitus or prior myocardial infarction
      for 1 year. RESULTS: Prescriptions of anti-hypertensive (from 1.3 +/- 0.8 to 1.4
      +/- 0.8 drugs per patient) and antihyperlipidemia drugs (from 0.70 +/- 0.4 to
      0.73 +/- 0.4 drugs per patient) did not significantly increase. Patient education
      for diet (93% to 97%, p = 0.077), exercise (69% to 81%, p < 0.05) and nonsmoking
      (66% to 86%, p < 0.05) significantly increased after 1 year. Blood pressure
      decreased from 142 +/- 16/81 +/- 10 to 138 +/- 78/78 +/- 9 mmHg (p < 0.05), serum
      total cholesterol level decreased from 215 +/- 39 to 203 +/- 39 mg/dl (p < 0.05).
      As a result, more patients attained the treatment goals recommended in the
      guidelines by the Japanese Society of Hypertension (34.6% to 46.8%) and Japan
      Atherosclerosis Society (40.2% to 49.5%), respectively. However, none of blood
      hemoglobin A1c level, body mass index or smokers significantly changed.
      CONCLUSIONS: Regional practitioners attempted to control all coronary risk
      factors. Hypertension and hyperlipidemia, which are relatively more dependent on
      the medical management, improved. In contrast, diabetes mellitus, obesity or
      smoking, which require life style changes, did not improve. The main issue in the
      risk factor management is how physicians act rather than specific actions.

PMID- 14658410
TI  - [Efficacy of intravenous myocardial contrast echocardiography for assessment of
      perfusion area of the heart in mice].
AB  - BACKGROUND AND OBJECTIVES: Intravenous myocardial contrast echocardiography is
      used clinically, but use in small animals has not been evaluated. The conditions
      for myocardial opacification and the feasibility of myocardial contrast
      echocardiography were examined in mice. METHODS: Closed chest mice were examined.
      The left ventricular short-axis view at the mid papillary muscle level was
      recorded before and after NC100100 injection using a SONOS 5500 (PHILIPS). Real
      time and intermittent triggering (every 5 beats) myocardial contrast
      echocardiography was performed with a mechanical index of low (0.3), middle
      (0.7), and high (1.5). Open chest mice were examined after left anterior
      descending coronary artery ligation. Myocardial contrast echocardiography was
      performed using intermittent triggering imaging (every 5 beats) with high
      mechanical index (1.5). The ratio of the non-perfused area to the whole left
      ventricular wall area was compared with that of the non-stained area by Evans
      Blue. RESULTS: The left ventricular myocardium was opacified in any setting. Good
      opacification was acquired at middle mechanical index (0.7) in real time
      myocardial contrast echocardiography and at high mechanical index (1.5) in
      intermittent myocardial contrast echocardiography. The opacified and non
      opacified myocardium were clearly identified in all mice with coronary ligation.
      The non-opacified area ratio showed a good correlation with the non-stained area
      ratio (y = 0.93x + 0.51, r = 0.94, p < 0.05). CONCLUSIONS: Myocardial contrast
      echocardiography can be used to assess myocardial perfusion and determine the
      ischemic area accurately in situ in the mouse.

PMID- 14658411
TI  - [Beneficial biventricular pacing in a patient with cardiac sarcoidosis and
      refractory heart failure: a case report].
AB  - A 54-year-old woman had been treated under a diagnosis of cardiac sarcoidosis
      since 1998. She was admitted to our department because of recurrent heart failure
      in April 2002. A DDD pacemaker was implanted because of complete AV block in
      2000, but she had always suffered from > or = New York Heart Association (NYHA)
      class III heart failure. To prevent recurrent heart failure, biventricular pacing
      was performed. The left ventricular epicardial pacing lead was newly inserted
      into the great cardiac vein via the left subclavian vein, and connected with the
      previously implanted generator. The QRS duration decreased from 200 to 140 msec.
      Serum brian natriuretic peptide level decreased from 321 to 226 pg/ml. Cardiac
      index increased from 1.93 to 2.20. Her functional class improved from NYHA class
      III to class II.

PMID- 14658412
TI  - [Brugada syndrome associated with ventricular fibrillation induced by
      administration of pilsicainide: a case report].
AB  - A 56-year-old man with Brugada syndrome presented with ventricular fibrillation
      induced by administration of pilsicainide. He had syncope at age 46 years, and
      his uncle suddenly died of unknown cause. He had taken pilsicainide (150 mg/day)
      for paroxysmal atrial fibrillation, and suffered from syncope due to ventricular
      fibrillation. Coved type ST elevation was observed in the V1 lead, and saddle
      back type ST elevation was observed in the V2 lead. The ST elevation gradually
      recovered after stopping pilsicainide therapy. No structural heart disease was
      found. After intravenous injection of pilsicainide, the ST segment elevated in
      the V1 and V2 leads. Ventricular fibrillation was induced by triple
      extrastimulation at the right ventricular apex. The diagnosis was Brugada
      syndrome, and a cardioverter-defibrillator was implanted. Brugada syndrome should
      be considered before administering pilsicainide.

PMID- 14658413
TI  - [Mediastinal mass occurring 26 years after coronary artery bypass grafting].

PMID- 14658414
TI  - Managing patients with restless legs.
AB  - Estimates suggest that around 10-15% of adults have restless legs, or Ekbom
      syndrome. This condition is characterised by a range of uncomfortable and
      sometimes distressing motor and sensory symptoms during quiet wakefulness and/or
      sleep, such as feelings of burning, tickling or crawling, pain, cramping,
      numbness or weakness in the lower limbs, and, sometimes, also in the trunk and
      arms. The problem can seriously affect quality of life, yet is frequently
      dismissed as trivial. Often, it is unrecognised, incorrectly regarded as a
      neurosis, or managed poorly or not at all. Here we review how people with
      restless legs can best be helped.

PMID- 14658415
TI  - Antibacterial prophylaxis in surgery: 1--Gastrointestinal and biliary surgery.
AB  - Two years ago, we reviewed systemic antibacterial prophylaxis for preventing
      infection after orthopaedic surgery. In this article, the first in a new series,
      we review the general principles governing antibacterial prophylaxis for
      preventing surgical-site infection (i.e. involving the wound, organs or spaces),
      and discuss prophylaxis for surgery on the gut and biliary system. Future
      articles will consider prophylaxis for obstetric, gynaecological and urogenital
      operations, and vascular surgery.

PMID- 14658416
TI  - Nicorandil for angina--an update.
AB  - Around 2 million people in the UK have angina pectoris and are therefore at high
      risk of severe coronary events such as myocardial infarction (MI) or sudden
      death. Conventional management of patients with stable angina includes glyceryl
      trinitrate, a beta-blocker, aspirin and a statin, with the aim of controlling
      symptoms and reducing the risk of a coronary event. For patients unable to
      tolerate a beta-blocker, the choice is less clear but calcium channel blockers
      and long-acting nitrates provide effective symptom control. Another option is
      nicorandil (Ikorel--Rhone-Poulenc Rorer), a potassium channel activator licensed
      for the "prevention and long term treatment of chronic stable angina pectoris".
      In our review of nicorandil 8 years ago, we concluded that it provided symptom
      control that was as good as, but no better than, other less expensive anti
      anginal drugs. Since then, new data have suggested that nicorandil might reduce
      the frequency of coronary events in patients with stable angina. Here, we
      consider these findings and reassess the place of nicorandil for patients with
      angina.

PMID- 14658417
TI  - [New medical therapies for the treatment of systolic heart failure].
AB  - Heart failure is characterized by sodium and fluid retention, sympathetic
      overactivation, parasympathetic withdrawal, vasoconstrictor activation and
      cytokine elevation. New therapies for heart failure attempt to control
      neurohormonal activation and limit progressive left ventricular dysfunction.
      Nesiritide (human B-type natriuretic peptide) is a recently approved new
      vasodilator that has been given to almost 1000 patients in numerous clinical
      investigations, it belongs to a new class of heart failure drugs known as
      natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure,
      systemic vascular resistance, mean right atrial pressure and pulmonary artery
      pressure, while improving cardiac index, stroke volume and heart failure
      symptoms. Many endothelin receptor antagonists are in various stages of
      development. Early clinical studies have demonstrated beneficial cardiovascular
      hemodynamic effects. Other new drugs for heart failure also include calcium
      sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosteron
      receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are
      being actively investigated and many show significant promise as beneficial
      therapies in the treatment of heart failure.

PMID- 14658418
TI  - [Role of CT and MR examinations in the assessment of nasopharyngeal tumors].

PMID- 14658419
TI  - [Chromium (III)-ion enhances the utilization of glucose in type-2 diabetes
      mellitus].
AB  - INTRODUCTION: The prevalence of the type 2 diabetes mellitus is still growing.
      Although the occurrence of insulin resistance is quite frequent in the whole
      population, diabetes not always develops because for a time the compensating
      mechanism avoids it. In a frequent variation of type-2 diabetes the disease is
      not the result of an alteration in the insulin receptor or the glucose
      transporter, but a genetically determined defect of the postreceptorial
      intracellular signaling mechanism plays a role in its occurrence. There have been
      investigations for decades to find out more about the role of chromium (III) ions
      in glucose metabolism and in the prevention of type-2 diabetes. It has also been
      investigated if chromium substitution can prevent or treat those forms of
      diabetes where chromium deficiency is suspected to be in the background of the
      disorder. AIM: The aim of our present investigation is to test the role of
      chromium (III) compounds in glucose metabolism that are known from literature.
      The authors examined the effect of oral chromium supplementation on antidiabetic
      treatment. Chromium supplementation was applied for 6 months. METHODS: Before,
      through and after the investigation changes in the patient's carbohydrate and
      lipid metabolism were followed by laboratory tests. RESULTS: At the end of our
      examination the cholesterin level significantly, the HbA1c level close to the
      significant value decreased. Due to their results the authors presume that
      chromium (III) compounds may be effective in the treatment of patients' with
      decreased glucose tolerance or type-2 diabetes mellitus as a supplement to their
      therapy.

PMID- 14658420
TI  - [T-wave alternans and Torsade de Pointes ventricular tachycardia in a patient
      with intracerebral hemorrhage].
AB  - A rare form of pause dependent form of torsade de pointes ventricular tachycardia
      and T-wave alternans is reported. The life-threatening ventricular arrhythmia was
      associated with left sided intracerebral hemorrhage and elevated CKMB mass and
      Troponin T (0.14 ng/ml). The possible pathomechanism of torsade de pointes
      tachycardia is discussed.

PMID- 14658421
TI  - [Treatment of oral candidiasis].

PMID- 14658422
TI  - [Treatment of pheochromocytoma].

PMID- 14658423
TI  - [Professor Tibor Risko is 80 years old].

PMID- 14658424
TI  - Transplantation for multiple myeloma: who, when, how often? Patient selection and
      goals.

PMID- 14658426
TI  - [Organization, management and economic aspects of the clinical laboratory
      service. Abstracts of the National Days of Laboratory Medicine in Russia 2003
      Scientific Symposium].

PMID- 14658425
TI  - [In honor of the 100th anniversary of E. A. Asratyan].

PMID- 14658428
TI  - Nuffield Council on Bioethics issues consultation paper on personalized
      medicines.

PMID- 14658429
TI  - Abbott and Tecan announce agreement for molecular diagnostics technology.

PMID- 14658430
TI  - Pro: non-penetrating glaucoma surgery--a fair chance.

PMID- 14658432
TI  - Pill safe way for women with gene mutation to lower risk of ovarian cancer.

PMID- 14658431
TI  - Contra: non-penetrating surgery and filtration?

PMID- 14658433
TI  - Key epilepsy research published--validating Bionomics ionX discovery platform.

PMID- 14658434
TI  - Study finds overwhelming majority of American consumers and physicians back
      development of personalized medicine.

PMID- 14658435
TI  - Gene find aids malaria fight.

PMID- 14658436
TI  - Aptamares: a novel class of radiopharmaceutical with diagnostic and therapeutic
      potential.

PMID- 14658437
TI  - [Report from the jubilee session of the Endocrinology and Metabolism Section of
      Human Development Committee, PAN, Warsaw].

PMID- 14658438
TI  - Oral health and health behavior in patients under anticoagulation therapy.

PMID- 14658439
TI  - South Africa's disease burden.

PMID- 14658440
TI  - Attitude and adherence.

PMID- 14658441
TI  - FDA debuts drug product catalog.

PMID- 14658442
TI  - HIV among migrant workers rising.

PMID- 14658443
TI  - New female birth control device.

PMID- 14658444
TI  - Rapid HIV test approved.

PMID- 14658445
TI  - [Are drug-coated stents too expensive?].

PMID- 14658446
TI  - Sarcomatoid salivary duct carcinoma of the oral cavity.
AB  - This report recounts a new case of sarcomatoid variant of salivary duct carcinoma
      in a 45-year-old woman. The 1.5-cm polypoid mass protruded from the retromolar
      area and focally extended into the pharyngeal wall. The patient was free of
      disease for 11 years. The tumor showed a biphasic malignancy; nondescript
      sarcomatous proliferation predominated over ductal carcinoma population, with
      perceptible blending of the two components. The sarcomatoid areas had no
      heterologous properties. Discohesive pleomorphic cells were immunopositive for
      vimentin, epithelial membrane antigen and AE1/AE3 at a significant rate. A dual
      expression of AE1/AE3 and vimentin was also evident in enmeshed foci of
      conventional cribriform adenocarcinoma. Thus, the sarcomatoid histology
      represents a dedifferentiated phenotype of salivary duct carcinoma.

PMID- 14658447
TI  - Testing participation in BRCA1/2-positive families: initiator role of index
      cases.
AB  - The objectives of this study were to: (1) describe diffusion of information by
      affected women in whom a mutation has been identified (index cases) to their
      families and testing participation among high-risk relatives; (2) assess
      information recall and understanding by index cases and their satisfaction with
      the testing process; and (3) determine the factors associated with higher/lower
      testing decision in the family. Thirty index cases completed a self-administered
      questionnaire assessing their personal and family characteristics and their
      satisfaction with their own genetic testing process and a telephone interview to
      evaluate their knowledge about the risk of a genetic predisposition to breast and
      ovarian cancer, the type and number of close relatives that they informed, and
      the difficulties that they encountered. Information about breast/ovarian cancer
      risk and test availability was generally well transmitted (75%), predominantly
      (88%) to first-degree relatives. In contrast, testing participation was low (15%)
      and essentially occurred among sisters and daughters. There was a general lack of
      knowledge despite a high level of satisfaction regarding the information given by
      the geneticist. Family support and the knowledge of index cases about the risk of
      transmission of BRCA1/2 mutations by women were found to be positively and
      significantly associated with the testing decision among first-degree relatives.
      Difficulties in informing relatives appeared to be related to poor understanding
      of the information by index cases, as well as fear, and avoidance among close
      relatives. A major challenge for genetic counseling is to ensure that consulting
      patients not only receive complete understanding but also understand this
      information and anticipate the impact of the test result before deciding to take
      the test.

PMID- 14658448
TI  - Resource use of insect seed predators during general flowering and seeding events
      in a Bornean dipterocarp rain forest.
AB  - Insect seed predators of 24 dipterocarp species (including the genera ot
      Dipterocarpus, Dryobalanops and Shorea) and five species belonging to the
      Moraceae, Myrtaceae, Celastraceae and Sapotaceae were investigated. In a tropical
      lowland dipterocarp forest in Sarawak, Malaysia, these trees produces seeds
      irregularly by intensely during general flowering and seeding events in 1996
      and/or 1998. Dipterocarp seeds were preyed on by 51 insect species (11 families),
      which were roughly classified into three taxonomic groups: smaller moths
      (Trotricidae, Pyralidae, Crambidae, Immidae, Sesiidae, and Cosmopterigidae),
      scolytids (Scolydae) and weevils (Curdulionidae, Apionidae, Anthribidae, and
      Attelabidae). Although the host-specificity of invertebrate seed predators has
      been assumed to be high in tropical forests, it was found that the diet ranges of
      some insect predators were relatively wide and overlapped one another. Most seed
      predators that were collected in both study years changes their diets between
      general flowering and seeding events. The results of cluster analyses based on
      the number of adult of each predator species that emerged from 100 seeds of each
      tree species, suggested that the dominant species was not consistent, alternating
      between the two years.

PMID- 14658450
TI  - Matiasmenos.

PMID- 14658449
TI  - Teaching the art of clinical practice: the veterinary medical teaching hospital,
      private practice, and other externships.

PMID- 14658451
TI  - Transplantation for multiple myeloma. Pertinent Questions.

PMID- 14658452
TI  - The space experiment of protein crystallization aboard the Chinese spacecraft SZ
      3.
AB  - Using new flight hardware, a Chinese mission of space protein crystallization has
      been performed aboard the Chinese spacecraft SZ-3. Preliminary analyses of the
      experimental results have shown that a few proteins produced better crystals in
      space. At least, the crystals of cytochrome b5 mutant could diffract X-ray beyond
      the highest resolution reported so far for the same kind of crystals. In
      addition, some rules derived from our numerical studies of the liquid/liquid
      diffusion protein crystallization were proved by the crystallization of lysozyme
      as model protein in this space experiment, which also clearly showed the
      advantages and disadvantages of the gelation of the protein solution used in
      microgravity growth of protein crystals.

PMID- 14658453
TI  - Gravitactic signal transduction elements in Astasia longa investigated during
      parabolic flights.
AB  - Euglena gracilis and its close relative Astasia longa show a pronounced negative
      gravitactic behavior. Many experiments revealed that gravitaxis is most likely
      mediated by an active physiological mechanism. The goal of the present study was
      to examine elements in the sensory transduction by means of inhibitors of
      gravitaxis and the intracellular calcium concentration during short microgravity
      periods. During the course of six parabolic flights (ESA 31th parabolic flight
      campaign and DLR 6th parabolic flight campaign) the effects of trifluoperazine
      (calmodulin inhibitor), caffeine (phosphodiesterase inhibitor) and gadolinium
      (blocks mechano-sensitive ion channels) was investigated. Due to the extreme
      parabolic flight maneuvers of the aircraft alternating phases of 1.8 x g(n)
      (about 20 s) and microgravity (about 22 s) were achieved (g(n): acceleration of
      Earth's gravity field). The duration of the microgravity periods was sufficient
      to detect a loss of cell orientation in the samples. In the presence of
      gadolinium impaired gravitaxis was found during acceleration, while caffeine
      treated cells showed, compared to the controls, a very precise gravitaxis and
      faster reorientation in the 1.8 x g(n) period following microgravity. A transient
      increase of the intracellular calcium upon increased acceleration was detected
      also in inhibitor-treated samples. Additionally, it was found that the cells
      showed a higher calcium signal when they deviated from the vertical swimming
      direction. In the presence of trifluoperazine a slightly higher general calcium
      signal was detected compared to untreated controls, while gadolinium was found to
      decrease the intracellular calcium concentration. In the presence of caffeine no
      clear changes of intracellular calcium were detected compared to the control.

PMID- 14658455
TI  - Procedure for simulating divergent-light halos.
AB  - Divergent-light halos are halos produced by light from nearby light sources, like
      street lamps being scattered by small crystals of ice floating in the air. The
      use of "brute-force" Monte Carlo methods to simulate such halos is extremely
      inefficient, as most scattered rays will not hit the eye of the observer. I
      present a new procedure for Monte Carlo simulations of divergent-light halos.
      This procedure uses rotational symmetries to make a selected sampling of events
      that greatly improves the computational efficiency of the algorithm. We can
      typically generate a simulated halo display in minutes using a personal computer,
      several orders of magnitude more rapid than a simple brute-force method. The
      algorithm can also optionally generate three-dimensional pictures of divergent
      light halo displays.

PMID- 14658456
TI  - Continuous hyperspectral absorption measurements of colored dissolved organic
      material in aquatic systems.
AB  - The majority of organic carbon in the oceans is present as dissolved organic
      matter (DOM); therefore understanding the distribution and dynamics of DOM is
      central to understanding global carbon cycles. Describing the time-space
      variability in colored dissolved organic matter (CDOM) has been difficult, as
      standard spectrophotometric methods for CDOM determination are laborious and
      susceptible to methodological biases. Previously, measurements of CDOM absorption
      in discrete water samples by use of a liquid-waveguide capillary cell (LWCC)
      compared favorably with measurements made with a benchtop spectrophotometer.
      Given this, we focused on automating the LWCC technique to improve our spatial
      and temporal sampling capabilities for CDOM. We found strong correlations between
      CDOM absorption spectra collected from discrete water samples using standard
      methods and selected corresponding CDOM spectra collected by the automated LWCC
      system. The near-continuous measurements by the LWCC system made it possible to
      map the temporal, spatial, and spectral variability of CDOM absorption along the
      ship track.

PMID- 14658454
TI  - Flexibility in system design and implications for aerospace systems.
AB  - The purpose of this paper is to review the concept of flexibility as discussed in
      various fields of investigations, to extract its characteristic features, and to
      explore its implications in the case of aerospace system design. In order to
      discuss any subject matter clearly, it is necessary to begin with a clear set of
      definitions. Indeed much can be gained through careful and consistent definitions
      of terms alone. Flexibility however is a word rich with ambiguity. While it is
      being increasingly used in various fields, few attempts have been made to
      formally define, quantify, and propose ways for achieving flexibility. This paper
      proposes to fill in part of this gap by synthesizing a clear and consistent
      definition of flexibility. It will do so by reviewing the usage of the term in
      various fields of inquiries, and show that it is indeed possible to clearly and
      unambiguously characterize flexibility, and to disentangle it from closely
      related concepts.

PMID- 14658457
TI  - Differential laser absorption spectrometry for global profiling of tropospheric
      carbon dioxide: selection of optimum sounding frequencies for high-precision
      measurements.
AB  - We discuss the spectroscopic requirements for a laser absorption spectrometer
      (LAS) approach to high-precision carbon dioxide (CO2) measurements in the
      troposphere. Global-scale, high-precision CO2 measurements are highly desirable
      in an effort to improve understanding and quantification of the CO2 sources and
      sinks and their impact on global climate. We present differential absorption
      sounding characteristics for selected LAS transmitter laser wavelengths,
      emphasizing the effects of atmospheric temperature profile uncertainties.
      Candidate wavelengths for lower-troposphere measurements are identified in the
      CO2 bands centered near 1.57, 1.60, and 2.06 microm.

PMID- 14658458
TI  - Antisymmetric grating coupler: experimental results.
AB  - The principle of an antisymmetric grating coupler was recently proposed
      theoretically as a planar waveguide add-drop multiplexer. It has the potential to
      enhance significantly the functionality of an add-drop multiplexer based on
      grating-assisted coupling. Here we realize the concept experimentally in an all
      fiber geometry. We show that conventional devices exhibit two high-reflection
      bands. In contrast, the antisymmetric grating coupler has only a single
      reflection band, thereby dramatically improving its filtering characteristics.

PMID- 14658459
TI  - Twin-rainbow metrology. I. Measurement of the thickness of a thin liquid film
      draining under gravity.
AB  - We describe twin-rainbow metrology, a new optical technique used to measure the
      thickness of thin films in a cylindrical geometry. We also present an application
      of the technique: measurement of the thickness of a Newtonian fluid draining
      under gravity. We compare these measurements with fluid mechanics models.

PMID- 14658460
TI  - Dynamic spectroscopic measurements of the temperature and pressure cycles in a
      MOPITT pressure modulator cell.
AB  - The temperature and pressure cycles inside a pressure modulator cell (PMC) of the
      type used for gas-correlation radiometry aboard the Measurements of Pollution in
      the Troposphere (MOPITT) satellite instrument have been determined from dynamic
      measurements of the spectral line shapes of the R(0) and R(18) transitions in the
      fundamental vibrational-rotational band of carbon monoxide. The line strengths
      and linewidths were used to calculate the temperature and pressure, respectively,
      with a temporal resolution of approximately 200 micros, or 1/100 of a PMC cycle.
      The results are compared with a thermodynamic box model.

PMID- 14658461
TI  - Optical nonreciprocal devices with a silicon guiding layer fabricated by wafer
      bonding.
AB  - Optical nonreciprocal devices with a silicon guiding layer fabricated by wafer
      bonding are proposed. The optical nonreciprocal devices are composed of a magneto
      optic waveguide with a magnetic garnet/Si/SiO2 structure. Nonreciprocal
      characteristics are obtained by an evanescent field penetrating into the upper
      magnetic garnet cladding layer. Several kinds of the optical nonreciprocal device
      are investigated with the magneto-optic waveguide and designed at a wavelength of
      1.55 microm. As a preliminary experiment, wafer bonding between Gd3Ga5O12 and Si
      was studied. Wafer bonding was successfully achieved with heat treatment at 220
      degrees C in H2 ambient.

PMID- 14658462
TI  - Performance analyses of flowing chemical oxygen-iodine laser.
AB  - A modified simplified rate-equation model that utilizes the Voigt profile
      function and another gain saturation model deduced from the kinetic equations are
      presented for performance analyses of a flowing chemical oxygen-iodine laser.
      Both models are adapted to both the condition of homogeneous broadening and that
      of inhomogeneous broadening being of importance and the condition of
      inhomogeneous broadening being predominant. Effects of temperature and iodine
      density on the output power and on variations of output power, optical intensity,
      and saturation intensity with flow distance are presented as well. There are
      differences between results of two models, but both qualitatively agree with
      known results.

PMID- 14658463
TI  - Generalized Lorenz-Mie theory for a spheroidal particle with off-axis Gaussian
      beam illumination.
AB  - The beam-shape coefficients of arbitrary off-axis Gaussian beams in spheroidal
      coordinates are evaluated with a generalized Lorenz-Mie theory. The light
      scattering properties of absorbing and nonabsorbing homogeneous spheroidal
      particles, such as the angular distribution of scattered intensity for a wide
      range of particles sizes and different complex refractive indices versus the
      magnitude and location of the beam waist, are investigated.

PMID- 14658464
TI  - Continuous-wave singly resonant optical parametric oscillator placed inside a
      ring laser.
AB  - A cw singly resonant optical parametric oscillator (SRO) was built and placed
      inside the cavity of a ring laser. The system consists of a diode-end-pumped
      Nd:YVO4 ring laser with intracavity periodically poled lithium niobate as the
      nonlinear gain medium of the SRO. When the laser was operated in a unidirectional
      mode, we obtained more than 520 mW of signal power in one beam. When the laser
      was operated in a bidirectional mode, we obtained 600 mW of signal power (300 mW
      in two separate beams). The power and the spectral features of the laser in the
      unidirectional and bidirectional modes were measured while the laser was coupled
      with the SRO. The results show that it is preferable to couple a SRO with a
      unidirectional ring laser.

PMID- 14658465
TI  - Optical feedback laser with a quartz crystal plate in the external cavity.
AB  - We studied the optical feedback characteristics of a single-mode He-Ne laser with
      a quartz crystal plate in the external cavity. The fringe frequency of the laser
      system can be doubled when the quartz crystal plate is positioned at a certain
      angle between the crystalline axis and the beam in the crystal plate. Theoretical
      analysis shows that the birefringent effect of the quartz crystal plate and the
      laser beam's second pass through the external cavity result in this phenomenon.
      The experimental results are in good agreement with the theoretical analysis. A
      quartz crystal plate can double the resolution of a self-mixing sensing system.

PMID- 14658466
TI  - Dual-color operation of a laser diode under current and temperature control.
AB  - We describe a novel method that operates a laser diode with dual colors. Our
      system requires no external optical parts but does require current and
      temperature control. We can use either a single color on a time-sharing basis or
      dual colors simultaneously. The difference between the wavelengths is -0.6 nm,
      which is as much as 10 times that generated by current control alone. Temporal
      stability of the generated two wavelengths and the response time of the
      wavelength change were confirmed through a number of experiments.

PMID- 14658467
TI  - Frequency stabilization of a laser diode with use of light-induced birefringence
      in an atomic vapor.
AB  - We present a simple modulation-free technique to stabilize a laser frequency to
      the Doppler-free spectra of an atomic vapor. Polarization spectroscopy with use
      of a balanced polarimeter allows us to obtain a background-free dispersion signal
      suitable for high-speed and robust frequency stabilization. We employed the
      method to the 5S(1/2) F = 2 --> 5P(3/2) F' = 3 transition of 87Rb atoms. The
      achieved feedback bandwidth was approximately 100 kHz, and an efficient
      suppression of the frequency noise in a laboratory environment was attained.

PMID- 14658468
TI  - Compact high-pulse-energy ultraviolet laser source for ozone lidar measurements.
AB  - An all solid-state Ti:sapphire laser differential absorption lidar transmitter
      was developed. This all-solid-state laser provides a compact, robust, and highly
      reliable laser transmitter for potential application in differential absorption
      lidar measurements of atmospheric ozone. Two compact, high-energy-pulsed, and
      injection-seeded Ti:sapphire lasers operating at a pulse repetition frequency of
      30 Hz and wavelengths of 867 and 900 nm, with M2 of 1.3, have been experimentally
      demonstrated and their properties compared with model results. The output pulse
      energy was 115 mJ at 867 nm and 105 mJ at 900 nm, with a slope efficiency of 40%
      and 32%, respectively. At these energies, the beam quality was good enough so
      that we were able to achieve 30 mJ of ultraviolet laser output at 289 and 300 nm
      after frequency tripling with two lithium triborate nonlinear crystals.

PMID- 14658469
TI  - Temperature-dependent dispersion equations for KTiOPO4 and KTiOAsO4.
AB  - We have measured the thermal expansion and the temperature dependence of z and y
      components of the refractive index for KTiOPO4 and KTiOAsO4, in the wavelength
      range 532-1585 nm and temperature range 25-200 degrees C, using an
      interferometric technique. The measurements were used to derive temperature
      dependent Sellmeier equations for the two materials. These equations predict with
      good agreement the temperature dependence of quasi-phase-matched nonlinear
      frequency converters.

PMID- 14658470
TI  - Relative measurements of second-order susceptibility with reflective second
      harmonic generation.
AB  - There is a strong demand for a simple and reliable technique for second-order
      susceptibility measurements of thin films. Since the Maker fringe technique is
      limited to transparent substrates we propose an experimental protocol based on
      reflective second-harmonic generation (SHG). The proposed protocol is based on
      relative measurements of Z-cut quartz. An analytical expression of the reflective
      SHG intensity dependence of the polarizer, analyzer, and sample azimuth is
      presented. An error analysis is also presented. Thin organic film of the side
      chain polymer poly(Disperse Red 1 Methacrylate-Co-Methyl-Methacrylate) is
      investigated. Results for different wavelengths are reported.

PMID- 14658471
TI  - All-optical wavelength conversion in a GaInAsP/InP optical gate loaded with a
      Bragg reflector.
AB  - All-optical wavelength conversion employing a GaInAsP/InP nonlinear distributed
      feedback waveguide switch is investigated. The device has the advantages of
      simple structure, compactness, polarity-noninverted operation, and feasibility of
      integration with other photonic devices such as semiconductor optical amplifier
      and modulators. We show that the device exhibits constant conversion efficiency
      around -9.2 dB in a signal-wavelength range of 1530-1560 nm. Furthermore, this
      device can potentially be made polarization independent.

PMID- 14658472
TI  - Continuous-wave operation of monolithically grown 1.5-microm optically pumped
      vertical-external-cavity surface-emitting lasers.
AB  - Continuous-wave operation, to as high as 7 degrees C, of 1.5-microm optically
      pumped vertical-external-cavity surface-emitting lasers is reported. The
      epitaxial structure, monolithically grown on InP by metal-organic chemical vapor
      deposition, consists of an InAlAs/GaInAlAs Bragg reflector, an InGaAs/InGaAsP
      active region, and an InP capping layer. The threshold incident pump intensity is
      <9 kW/cm2.

PMID- 14658473
TI  - Nitric-oxide planar laser-induced fluorescence applied to low-pressure hypersonic
      flow fields for the imaging of mixture fraction.
AB  - The scalar-field imaging of a hypersonic mixing flow is performed in a mixing
      facility that is shock tunnel driven. The instantaneous mixture-fraction field of
      a hypersonic two-dimensional mixing layer (M1 = 5.1, M2 = 0.3) is determined with
      a temperature-insensitive planar laser-induced fluorescence technique with nitric
      oxide (NO) as the tracer species. Single-shot images are obtained with the
      broadband excitation of a reduced temperature-sensitivity transition in the A2
      sigma+ <-- X2 II(1/2) (0, 0) band of NO near 226 nm. The instantaneous mixture
      fraction field at a convective Mach number of 2.64 is shown to be nearly
      identical to a typical diffusive process, supporting the notion of gradient
      transport mixing models for highly compressible mixing layers.

PMID- 14658474
TI  - Passive standoff detection of Bacillus subtilis aerosol by Fourier-transform
      infrared radiometry.
AB  - An analysis is presented on the passive standoff detection and identification of
      Bacillus subtilis (BG) clouds with the Compact ATmospheric Sounding
      Interferometer (CATSI) sensor. This research is based on recent spectral
      measurements obtained during the Technology Readiness Evaluation trial held July
      2002 at Dugway Proving Ground, Utah. Results obtained from three trial BG cloud
      episodes are used to explain and demonstrate the detection capability of the
      CATSI sensor. The BG clouds were measured at a distance of 3 km from the sensor
      in a near-horizontal path scenario. It was found that the low thermal contrast of
      approximately 0.2 K between the BG cloud and the background yielded weak but
      observable spectral signatures. The processing of the spectral signatures with
      the GASeous Emission Monitoring (GASEM) algorithm has provided a rough estimate
      of BG cloud column densities. The results of a series of simulations with the
      FASCOD3 transmission model have shown that the detection sensitivity for BG can
      be greatly improved for both slant path uplooking and downlooking scenarios.

PMID- 14658475
TI  - Measurement of the bulk viscosity of liquid by Brillouin scattering.
AB  - The aim is to develop a rapid and direct method for measuring the bulk viscosity
      of a liquid as a function of temperature. Brillouin scattering of a laser beam in
      fresh water and salt water at different temperatures has been studied. The
      results show that there exists a close temperature-dependent relationship among
      the Brillouin frequency shift, the Brillouin linewidth, and the bulk viscosity of
      water. Thus the bulk viscosity of water can be determined directly from Brillouin
      scattering measurements. The method has a high signal-to-noise ratio and high
      accuracy.

PMID- 14658476
TI  - Yet another look at light scattering from particles in absorbing media.
AB  - We examine the scattering properties of particles contained in absorbing media.
      Rather than consider energy fluxes through arbitrary integrating spheres, we
      examine the extinction from its fundamental definition: the energy removed from
      the plane wave, or incident beam. The resulting energy received by a detector
      contains two terms: one the result of the incident beam traversing through the
      medium that would have occurred if the particle were not present, and a
      correction term due to the presence of the particle. Both terms have the same
      dependence on the pathlength that the beam travels between two arbitrarily
      located parallel planes and are independent of where the particle is located
      within the medium. The result is that the definition of the extinction cross
      section is not dependent on a reference plane or the particle location within the
      medium.

PMID- 14658477
TI  - Wavelength modulation spectroscopy: combined frequency and intensity laser
      modulation.
AB  - A theoretical model of wavelength modulation spectroscopy that uses a laser diode
      on a Lorentzian absorption line is presented. This theory describes the general
      case of a current-modulated semiconductor laser, for which a combined intensity
      and frequency modulation with an arbitrary phase shift occurs. On the basis of
      this model, the effect of several modulation parameters on the detected signals
      is evaluated. Experimental signals measured on an absorption line of CO2 by use
      of a 2-microm distributed-feedback laser are also presented and validate this
      analysis. These experimental results agree with the calculated signals,
      confirming the relevance of the model.

PMID- 14658478
TI  - Tunable ultraviolet laser-induced fluorescence detection of trace plastics and
      dissolved organic compounds in water.
AB  - We developed a tunable (220-285-nm) UV and fixed 266-nm laser-induced
      fluorescence (LIF) system using a spectrometer and a cooled CCD imaging detector
      to measure the excitation-emission matrix spectra of various compounds in water,
      including quinine sulfate and plastic compound bisphenol-A. The LIF instrument
      was used for the fast, nonspecific determination of trace amounts of dissolved
      organic compounds present in natural water supplies and various brand name
      bottled distilled water and bottled drinking water. Plastic-related compounds
      that leached out of plastic utensils and containers were also detected with this
      instrument. The sensitivity of the system was approximately 1-2 orders of
      magnitude better than that for a commercial system.

PMID- 14658479
TI  - Development and initial calibration of a portable laser-induced fluorescence
      system used for in situ measurements of trace plastics and dissolved organic
      compounds in seawater and the Gulf of Mexico.
AB  - A portable UV laser-induced fluorescence system that uses a high pulsed
      repetition frequency (8-kHz) microchip laser at 266 nm, 13 switchable optical
      filters, and a gated photomultiplier tube detector has been developed and tested
      successfully for the detection of leached plastics (possibly bisphenol-A) and
      trace dissolved organic compounds in seawater. The instrument is 100 times more
      sensitive than commercial portable spectrofluorometers and measures a complete
      fluorescence spectrum in a moderate time period of 1-2 min. The system was tested
      in the Gulf of Mexico over varying water masses. In addition, fluorescence
      lifetime, bleaching, and temporal flow characteristics were studied.

PMID- 14658480
TI  - High-resolution broadband N2 coherent anti-Stokes Raman spectroscopy: comparison
      of measurements for conventional and modeless broadband dye lasers.
AB  - We have performed high-resolution N2 coherent anti-Stokes Raman spectroscopy
      (CARS) measurements using a modeless dye laser (MDL) as the Stokes beam source to
      determine the effects of a reduction in mode noise on the accuracy and precision
      of the method. These results are compared with previous research that employed a
      conventional broadband dye laser (CBDL) as the Stokes beam source. A new spectral
      fitting procedure was developed to avoid starting-point bias in the least-squares
      fitting results, which possibly had altered the previous measurements. Single
      shot measurements of pressure were performed in a static-pressure vessel over the
      range of 0.1-4.0 atm to examine the pressure sensitivity of the technique. The
      precision of these measurements is a measure of the baseline noise level of the
      system, which sets the detection limit for flow-field pressure fluctuations.
      Centerline measurements of pressure and temperature in an underexpanded jet (Mj =
      1.85) were also used to determine the performance of the technique in a
      compressible flow field. Our study represents the first known application, to our
      knowledge, of a MDL CARS system in a low-temperature, low-pressure supersonic
      environment. Improvements in accuracy for mean single-shot measurements and
      increased precision were found for pressure vessel conditions above 1.0 atm. For
      subatmospheric pressure vessel conditions (0.1-1.0 atm) and the underexpanded jet
      measurements, there was a decrease in accuracy and precision compared with the
      CBDL results. A comparison with the CBDL study is included, along with a
      discussion of the MDL system behavior.

PMID- 14658481
TI  - Self-compression and Raman soliton generation in a photonic crystal fiber of 100
      fs pulses produced by a diode-pumped Yb-doped oscillator.
AB  - We present the use of a photonic crystal fiber to straightforwardly compress
      ultrashort pulses from a diode-pumped ytterbium laser emitting around 1 microm.
      75-fs pulse generation and a large 1-1.3-microm tunability for sub-100-fs pulses
      is reported.

PMID- 14658482
TI  - Comparisons between allogeneic peripheral blood stem cell transplantation and
      allogeneic bone marrow transplantation in adult hematologic disease: a single
      center experience.
AB  - This retrospective study compared the outcomes in 32 adult patients with
      hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia,
      chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia) who
      received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28
      years) or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18;
      median age, 29 years) from human leukocyte antigen-identical sibling donors.
      Median follow-up was 58 months in BMT recipients and 18 months in PBSCT
      recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001) and platelet
      engraftment (median, Day 9 vs Day 17, p < 0.001) was faster in the PBSCT group
      than in the BMT group. Patients receiving PBSCT required less platelet
      transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001),
      but there was no significant difference in red cell transfusion. At 100 days,
      there was no difference in the incidence of acute graft-versus-host disease
      (GVHD) (42.9% vs 33.3%, p = 0.72) or grade II-IV acute GVHD (14.3% vs 5.6%, p =
      0.57), and there was no difference in the cumulative incidence of chronic GVHD
      (20% vs 33.3%, p = 0.67). No chronic GVHD was noted in any relapsed patients
      (BMT, 5; PBSCT, 3), and no patients with chronic GVHD during follow-up had a
      relapse. Relapse was the most frequent cause of death inboth groups (BMT, 5/9,
      55.6%; PBSCT, 3/4, 75%; p = 0.25); all relapses occurred within 1 year after
      transplantation. Overall survival was significantly better in the PBSCT group
      (35.7% vs 77.8%, p = 0.029), but this difference was lost if only hematologic
      malignancies were analyzed (30.8% vs 63.6%, p = 0.20). Our results are similar to
      those reported previously, with faster neutrophil and platelet engraftment and
      less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is
      a feasible and beneficial alternative to allogeneic BMT in adult hematologic
      disease.

PMID- 14658483
TI  - Eyelid tumors in southern Taiwan: a 5-year survey from a medical university.
AB  - This retrospective case analysis investigated the epidemiology of eyelid tumors
      in a subtropical area. The study assessed the proportion of all eyelid tumors
      that were malignancies, the accuracy of diagnosis, and surgical results. We
      retrospectively collected all cases of eyelid tumors in the Department of
      Ophthalmology, Kaohsiung Medical University, Taiwan, between January 1994 and
      December 1998. Among the 144 cases collected, about half of the tumors were
      located in the upper eyelids and the other half in the lower eyelids. Nearly 50%
      of cases underwent tumor resection with eyelid reconstruction. When followed up
      to April 1999, 97% of patients were satisfied with the surgical results. There
      were 18 cases (12.5%) of malignant tumors, including 14 basal cell carcinomas,
      three sebaceous carcinomas, and one squamous cell carcinoma. Before surgery, two
      malignancies were presumed to be benign tumors while another two were thought to
      be different malignant tumors. The benign tumors included 38 nevi, 15 squamous
      papillomas, 13 cysts, 11 verrucae, 10 seborrheic keratoses, four hemangiomas, and
      others. All tumors that were thought to be malignancies were treated using
      complete resection with margin monitoring by frozen section. At the end of follow
      up, no recurrence was noted. More than 10% of cases of eyelid tumors in this
      subtropical teaching hospital were malignant. All surgeons should be alert to
      this phenomenon when they operate on an eyelid tumor. The best policy is to send
      all specimens for pathologic examination.

PMID- 14658484
TI  - Immunohistochemical localization of endothelin-converting enzyme-1 in
      neuroendocrine tumors and normal human tissue.
AB  - Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin
      biosynthesis, catalyzing the final step in the process. In this study, we
      investigated the cellular distribution of ECE-1 in 19 normal human tissues and 16
      neuroendocrine tumors using immunohistochemical staining with antigen retrieval.
      ECE-1 was expressed in vessel endothelial cells as well as nearly all epithelial
      cells, glands and duct cells in normal human tissues including the esophagus,
      stomach, small intestine, appendix, colon, liver, gallbladder, pancreas,
      endometrium, cervix, breast, skin, prostate, urinary bladder, lung, kidney,
      sympathetic ganglion, thyroid gland, and adrenal gland. The most interesting
      finding was that ECE-1 was expressed in normal neuroendocrine cells. ECE-1 was
      also expressed in all 16 neuroendocrine tumors, including three paragangliomas,
      five pheochromocytomas, three carcinoid tumors, four medullary carcinomas of the
      thyroid, and one islet cell tumor of the pancreas. In conclusion, ECE-1 is
      enriched in neuroendocrine cells and neuroendocrine tumors, suggesting an
      important biologic role for the enzyme in the neuroendocrine system.

PMID- 14658485
TI  - Spinal process landmark as a predicting factor for difficult epidural block: a
      prospective study in Taiwanese patients.
AB  - Although epidural anesthesia is a common practice in neuraxial blockade,
      difficult access to the epidural space is a frequent problem in operating
      theaters. We designed this study of epidural blocks to determine if the spinal
      landmark grading system is valuable in predicting a difficult epidural block.
      Before the epidural block, we collected the following data: demographics, body
      habitus (normal, thin, obese, pregnant), spinal anatomy (normal, deformed),
      spinal level (lumbar, thoracic), and spinal landmark grade (grade 1: spinous
      processes visible; grade 2: spinous processes not seen but easily palpated; grade
      3: spinous processes not seen and not palpated but the interval between them is
      palpated as a low landmark under the thumb; grade 4: other). We performed all 848
      epidural blocks initially using a midline approach and an 18-gauge Touhy needle.
      We evaluated the technical difficulty of the epidural block using three methods:
      whether the epidural block was accomplished at the spinal level (first-level
      success); the total number of attempts at skin puncture (attempts-S); and total
      number of attempts to change ligament puncture direction (attempts-L) required to
      complete the epidural block. Of all examined factors, spinal landmark grade
      correlated best with technical difficulty as measured by all three methods.
      Deformed spinal anatomy and body habitus both correlated with difficulty, merely
      from the total numbers of attempts (attempts-S and attempts-L). Thoracic
      epidurals were more difficult than lumbar epidurals by all three measures of
      difficulty. We concluded that this spinal landmark grading system is valuable in
      predicting a difficult epidural block and advocate its use as a predictor by
      anesthesiologists.

PMID- 14658486
TI  - Pelvic congestion syndrome--findings on multi-detector row computerized
      tomography: a case report.
AB  - Chronic pelvic pain is a common gynecologic complaint, sometimes without any
      obvious etiology. We report a case of pelvic congestion syndrome with chronic
      pelvic pain. The diagnosis can be overlooked by clinical physicians but diagnosed
      using multi-detector row computerized tomography. This method seems to be an
      effective and non-invasive imaging modality.

PMID- 14658487
TI  - Spironolactone-induced agranulocytosis: a case report.
AB  - A 43-year-old woman with liver cirrhosis and hepatocellular carcinoma was
      admitted for the chief problem of ascites. Laboratory data revealed a leukocyte
      count of 3.8 x 10(9)/L on the second day of admission. Spironolactone was
      prescribed for diuresis beginning on the third day. Routine blood tests on the
      tenth day disclosed marked leukopenia (1.8 x 10(9)/L). Four days later, the
      leukocyte count was still 1.8 x 10(9)/L and a differential count revealed
      agranulocytosis (neutrophils, 0.25 x 10(9)/L). Eight days after withdrawal of
      spironolactone, the leukocyte count returned to normal (leukocytes, 4.9 x 109/L;
      neutrophils, 1.76 x 10(9)/L). On review of the patient's clinical condition,
      concurrent medication, and previous reports, we highly suspected that this
      episode of agranulocytosis was caused by spironolactone. Unlike four previously
      reported cases, this one did not involve furosemide, which is reported to be
      associated with leukopenia and agranulocytosis.

PMID- 14658488
TI  - Giant extrarenal retroperitoneal angiomyolipoma: a case report and literature
      review.
AB  - Extrarenal angiomyolipoma is an uncommon disease entity and is rare in the
      retroperitoneum. We report a case of giant extrarenal retroperitoneal
      angiomyolipoma mimicking liposarcoma. A 35-year-old woman presented with a
      history of increased abdominal circumference and urinary frequency. Abdominal
      computerized tomography demonstrated a 24 x 21 x 16 cm retroperitoneal fatty
      tumor displacing the right kidney to the left upper quadrant of the abdomen. At
      laparotomy, the tumor was widely excised and the right kidney was successfully
      preserved. Final histologic examination identified the tumor as an
      angiomyolipoma. At 4-month postoperative follow-up, no evidence of tumor
      recurrence was found and the right kidney was fully functional.

PMID- 14658489
TI  - Hyalinizing spindle cell tumor with giant rosettes: a case report.
AB  - Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) is characterized by
      both giant rosette-like structures with collagen cores sparsely distributed
      throughout the tumor and fibromyxoid stroma. It is a rare low-grade sarcoma with
      indolent behavior, and wide excision with long-term follow-up is the best
      treatment. Although originally considered a distinct entity, it is now regarded
      as a variant of low-grade fibromyxoid sarcoma. We present a case of HSCTGR
      arising in the deep soft tissue of the left knee in a 50-year-old woman and
      provide a brief review of the literature for comparison.

PMID- 14658490
TI  - Meeting report: EMBO workshop "Pathogenesis of amoebiasis: from genomics to
      disease", Institut Pasteur, Paris, May 19-22, 2003.

PMID- 14658491
TI  - Protofilament ribbon compartments of ciliary and flagellar microtubules.

PMID- 14658492
TI  - Pseudocysts in trichomonads--new insights.
AB  - Tritrichomonas foetus and Trichomonas vaginalis, parasitic protists of the
      urogenital tract, display a trophozoite and a pseudocyst stage. The
      ultrastructure of the trophozoite was compared with the pseudocyst form. The
      latter appears under unfavorable environmental conditions when the flagella are
      internalized, and a true cell wall is not formed. Although some authors consider
      this form as a degenerate stage, the cell behaves as a resistant form.
      Pseudocysts were found in natural culture conditions and also under induction by
      hydroxyurea or cycles of cooling and warming cultures. They were studied by light
      and scanning and transmission electron microscopy, using immunofluorescence and
      videomicroscopy. This report presents evidence that the trichomonad pseudocysts
      appear under stress conditions and that they are competent to divide. Pseudocysts
      differ from trophozoites in that: (1) the flagella are located in endocytic
      vacuoles and remain beating; (2) the axostyle and the costa are not depolymerized
      but present a curved shape; (3) the axostyle does not exhibit staining with
      antitubulin antibodies when the mitotic spindle is observed; (4) the mitotic
      process occurs within pseudocysts but differs from that described for
      trophozoites; (5) a nuclear canal is formed connecting the two spindle poles; and
      (6) the process is reversible if the cells are transferred to fresh medium.

PMID- 14658493
TI  - Aplanochytrium stocchinoi: a new Labyrinthulomycota from the southern ocean (Ross
      Sea, Antarctica).
AB  - Aplanochytrium stocchinoi, a new species of Labyrinthulomycota, is described from
      samples collected in Antarctica. Ultrastructural, life cycle and molecular data
      characterizing the new taxon are provided and compared with the features of other
      species included in the genus Aplanochytrium. The phylogenetic position of A.
      stocchinoi is investigated using the 18S rDNA as molecular marker and applying
      maximum parsimony, minimum evolution and maximum likelihood methods.

PMID- 14658494
TI  - Phylogeny and classification of phylum Cercozoa (Protozoa).
AB  - The protozoan phylum Cercozoa embraces numerous ancestrally biciliate
      zooflagellates, euglyphid and other filose testate amoebae, chlorarachnean algae,
      phytomyxean plant parasites (e.g. Plasmodiophora, Phagomyxa), the animal
      parasitic Ascetosporea, and Gromia. We report 18S rRNA sequences of 27 culturable
      zooflagellates, many previously of unknown taxonomic position. Phylogenetic
      analysis shows that all belong to Cercozoa. We revise cercozoan classification in
      the light of our analysis and ultrastructure, adopting two subphyla: Filosa
      subphyl. nov. a clade comprising Monadofilosa and Reticulofilosa, ranked as
      superclasses, ancestrally having the same very rare base-pair substitution as all
      opisthokonts; and subphylum Endomyxa emend. comprising classes Phytomyxea
      (Plasmodiophorida, Phagomyxida), Ascetosporea (Haplosporidia, Paramyxida,
      Claustrosporida ord. nov.) and Gromiidea cl. nov., which did not. Monadofilosa
      comprise Sarcomonadea, zooflagellates with a propensity to glide on their
      posterior cilium and/or generate filopodia (e.g. Metopion; Cercomonas;
      Heteromitidae - Heteromita, Bodomorpha, Proleptomonas and Allantion) and two new
      classes: Imbricatea (with silica scales: Euglyphida; Thaumatomonadida, including
      Alias, Thaumatomastix) and Thecofilosea (Cryomonadida; Tectofilosida ord. nov. -
      non-scaly filose amoebae, e.g. Pseudodifflugia). Reticulofilosa comprise classes
      Chlorarachnea, Spongomonadea and Proteomyxidea (e.g. Massisteria, Gymnophrys, a
      Dimorpha-like protozoan). Cercozoa, now with nine classes and 17 orders (four
      new), will probably include many, possibly most, other filose and reticulose
      amoebae and zooflagellates not yet assigned to phyla.

PMID- 14658495
TI  - Spatial distribution of gymnamoebae (Rhizopoda, Lobosea) in brackish-water
      sediments at the scale of centimeters and millimeters.
AB  - In order to study micro-spatial distribution of amoebae, an intact slice of sandy
      sediment from the brackish-water Niva Bay (Baltic Sea, The Sound), 40 x 24 mm in
      size and 2 mm in thickness was gently sectioned into cubes, 2 x 2 x 2 mm in size.
      Each cube was inoculated into enrichment media to reveal the biodiversity of
      amoebae. Seventeen species of amoebae were recovered. The 2-D map of amoebae
      species distribution in the slice, consisting of 240 2 x 2 mm cells was drawn and
      analyzed. Results show heterogeneous distribution of amoebae at the scale of
      centimeters and millimeters and confirm the idea of the presence of
      microhabitats, selectively occupied by amoebae species. Three types of
      distribution patterns were found: random, aggregated and equally spaced.
      Microelectrode studies indicated that amoebae distribution was not related to the
      dissolved oxygen content in the sediment. The studied slice of sediment contained
      several pronounced "hotspots" of amoebae biodiversity, where up to four species
      co-occur in the same area. Seven species of amoebae numbered 1-4 specimens in the
      studied slice (i.e. there was 0.5-2 cell ml(-1)). Analysis of the amoebae
      distribution map shows the high probability of undersampling rare amoebae species
      during faunistic studies.

PMID- 14658496
TI  - Revision of the genus Cryptomonas (Cryptophyceae): a combination of molecular
      phylogeny and morphology provides insights into a long-hidden dimorphism.
AB  - Seventy-three strains of cryptophytes assigned to the genera Cryptomonas,
      Campylomonas or Chilomonas were studied by light microscopy, spectrophotometry
      and whole-mount electron microscopy. Twelve groups of strains were distinguished
      by light and whole mount electron microscopy using a combination of characters,
      mainly cell size, type of periplast and presence/absence and number of pyrenoids.
      However, characters previously used to distinguish Cryptomonas from Campylomonas
      (e.g. the type of periplast: polygonal periplast plates vs. a continuous
      periplast sheet) were found to occur together in dimorphic strains, indicating
      that periplast types relate to different life-history stages of a single taxon.
      To evaluate the taxonomic significance of the type of periplast and other
      characters previously used to distinguish genera and species, representatives of
      each strain group were subjected to molecular phylogenetic analyses using two
      nuclear ribosomal DNA regions (ITS2, partial LSU rDNA) and a nucleomorph
      ribosomal gene (SSU rDNA). The results of the phylogenetic study provide
      molecular evidence for a life history-dependent dimorphism in the genus
      Cryptomonas: the genus Campylomonas represents the alternate morph of
      Cryptomonas. Campylomonas and Chilomonas are reduced to synonyms of Cryptomonas,
      the genus Cryptomonas is revised and typified, two new species are described and
      six species are emended.

PMID- 14658497
TI  - Cryptic freshwater ciliates in a hypersaline lagoon.
AB  - Ubiquitous dispersal of free-living microbial species implies that each and every
      ecosystem supports a 'seedbank' of microbial species that are imported by random
      dispersal. However, many of the microbial species present in any particular
      ecosystem will probably never thrive there because the local environment is
      unsuitable for their population growth. To test this, we investigated the
      ciliated protozoa in a hypersaline lagoon in Almeria, Spain, using selective
      enrichment to reveal typical freshwater species, as the 'signature' of random
      dispersal. Twenty-four ciliate species, 14 of them not previously recorded from
      hypersaline waters, were identified in the undiluted waters of the lagoon. But
      when the salinity was gradually diluted, further species typical of fresh- and
      brackish waters emerged, indicating that they had persisted in a viable state at
      the previously high salinity. These additional species increased the recorded
      ciliate species total for the lagoon to 36. The species found in the lagoon
      appeared to be adapted to either high, or variable, or low salinity, implying
      that they may have originated in a variety of habitats that differed greatly with
      respect to salinity regime.

PMID- 14658498
TI  - Mutation of the Dictyostelium fbxA gene affects cell-fate decisions and spatial
      patterning.
AB  - Cell-fate decisions and spatial patterning in Dictyostelium are regulated by a
      number of genes. Our studies have implicated a gene called fbxA, which codes for
      an F-box protein, in these pathways. The FbxA protein is one of the controls on a
      cAMP phosphodiesterase called RegA, mediating its degradation via ubiquitin
      linked proteolysis. Using marked strains, we showed that the fbxA- mutant has
      defective cell-type proportioning, with a dearth of prestalk cells compared to
      prespore cells. In this work, we show that this effect occurs earlier during the
      24 hour developmental cycle than previously thought. The normal sorting of the
      prestalk and prespore cells in aggregates and mounds is not affected by the
      mutation. The mutant cells sort abnormally at the tipped mound stage, when
      prespore and prestalk cells normally distribute into their proper compartments.
      The fbxA- mutant forms pre-stalk cells in low numbers when not in chimeras, but
      in the presence of wild-type amoebae the mutant preferentially forms viable
      spores, driving the wild type to form non-viable stalk cells. In an attempt to
      identify the signal transduction pathway that mediates proportionality in
      prestalk and prespore cells, we asked whether certain signal transduction mutants
      were immune to the effects of the fbxA- cells and formed spores in chimeras.

PMID- 14658499
TI  - Cloning and sequencing of four new metallothionein genes from Tetrahymena
      thermophila and T. pigmentosa: evolutionary relationships in Tetrahymena MT
      family.
AB  - The structure of four new MT (metallothionein) genes of Tetrahymena thermophila
      and T. pigmentosa were characterized. The MT-2 genes from the two species are
      very similar, differing by 10 out of 2259 sequenced nucleotides, and the deduced
      amino acid sequences are identical. The MT-1 genes from T. pigmentosa and T
      thermophila are also very similar, differing only by 3 nucleotides in the 5'-UT
      region. The promoter regions contain a TATA box and many stretches partially
      matching some regulatory elements such as metal-responsive (MREs), antioxidant
      responsive (AREs), a CAAT box, a G-box, and AP1 and ACE-1 binding sites. The
      related coding and amino acid sequences were compared with those previously
      sequenced in Tetrahymena. This analysis revealed two independent events of
      duplication occurring in Cd- (MT-1 and MTT1) and Cu- (MT-2) induced MTs. This
      evolutionary pathway also explains the unusual length of these proteins, which
      are much longer than many MTs studied so far. Additionally, the orthology and
      paralogy relationships of the various MTs are presented. Finally, on the basis of
      phylogenetic analyses of Tetrahymena MTs, two evolutionary hypotheses are
      proposed.

PMID- 14658500
TI  - An enigmatic GAPDH gene in the symbiotic dinoflagellate genus Symbiodinium and
      its related species (the order Suessiales): possible lateral gene transfer
      between two eukaryotic algae, dinoflagellate and euglenophyte.
AB  - A group of unicellular eukaryotic algae, the dinoflagellates, are known to
      possess two types of gene for glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
      An enzyme encoded by one type of gene possibly plays a key role in the glycolytic
      pathway of the cytosol and the other in the Calvin cycle of plastids. In the
      present study, an additional type of GAPDH gene (GapC3) was found in the
      symbiotic dinoflagellates, Symbiodinium spp. and their related species,
      Gymnodinium simplex and Polarella glacialis, all of which belong to the order
      Suessiales. Since no intracellular translocation signal is found at both amino-
      and carboxy-termini of its deduced amino acid sequence, the protein is predicted
      to function in the cytosol. However, it may not be involved in glycolysis due to
      the presence of an amino acid signature that allows binding for NADP+. It is
      likely that dinoflagellate species, other than Suessiales investigated in this
      study, lack this type of GAPDH. Phylogenetic analysis placed GapC3 from the
      Suessialean species firmly in the clade composed of GAPDH from spirochetes,
      euglenophytes (cytosolic type) and kinetoplastids (glycosomal type).
      Specifically, this enigmatic GAPDH gene in dinoflagellates was closely related to
      its cytosolic counterpart in euglenophytes. It has been previously reported that
      plastid-targeted (Calvin cycle) GAPDH genes of the dinoflagellates Pyrocystis
      spp. and that of the euglenophyte Euglena gracilis also seem to share a common
      ancestor. It appears highly likely that at least two genes (cytosolic and plastid
      targeted GAPDH genes) have been laterally transferred between these two
      eukaryotic algal groups.

PMID- 14658501
TI  - Andre Lwoff (1902-1994), Nobel Prize of Medicine, as protistologist.

PMID- 14658502
TI  - Prof. Dr. Lothar Jaenicke--80 years.

PMID- 14658503
TI  - Binding and toxicity of Bacillus thuringiensis protein Cry1C to susceptible and
      resistant diamondback moth (Lepidoptera: Plutellidae).
AB  - We studied mechanisms of resistance to Bacillus thuringiensis insecticidal
      crystal protein Cry1C in the diamondback moth, Plutella xylostella (L.). Binding
      assays with midgut brush border membrane vesicles prepared from whole larvae
      showed no significant difference between resistant and susceptible strains in
      binding of radioactively-labeled Cry1C. These results indicate that reduced
      binding of Cry1C to midgut membrane target sites did not cause resistance to
      Cry1C. Thus, the mechanism of resistance to Cry1C differs from that observed in
      several previously reported cases of resistance to Cry1A toxins in diamondback
      moth. We tested Cry1C toxin and Cry1C crystalline protoxin against resistant and
      susceptible larvae using leaf disk bioassays. After adjusting for the size
      difference between Cry1C toxin and protoxin, we found that with resistant larvae,
      toxin was significantly more toxic than protoxin. In contrast, with susceptible
      larvae, no significant difference in toxicity occurred between Cry1C toxin and
      protoxin. The resistance ratios for Cry1C were 19 for toxin and 48 for protoxin.
      These results suggest that reduced conversion of Cry1C protoxin to toxin is a
      minor mechanism of resistance to Cry1C. Because neither reduced binding nor
      reduced conversion of protoxin to toxin appear to be major mechanisms, one or
      more other mechanisms are important in diamondback moth resistance to Cry1C.

PMID- 14658504
TI  - Larval susceptibility of an insecticide-resistant western corn rootworm
      (Coleoptera: Chrysomelidae) population to soil insecticides: laboratory
      bioassays, assays of detoxification enzymes, and field performance.
AB  - Soil insecticides were evaluated in laboratory and field studies against larvae
      of an insecticide resistant population (Phelps County, NE) of western corn
      rootworm, Diabrotica virgifera virgifera LeConte. Insecticide toxicity was
      evaluated by topical application of technical insecticides to 3rd instars from
      Saunders County, NE (susceptible) and Phelps County populations. Resistance
      ratios (LD50 Phelps County/LD50 Saunders County) for the insecticides methyl
      parathion, tefluthrin, carbofuran, terbufos, and chlorpyrifos were 28.0, 9.3,
      8.7, 2.6 and 1.3, respectively. Biochemical investigation of suspected enzymatic
      resistance mechanisms in 3rd instars identified significant elevation of esterase
      activity (alpha and beta naphthyl acetate hydrolysis [3.8- and 3.9-fold]).
      Examination of 3rd instar esterases by native PAGE identified increased intensity
      of several isoenzymes in the resistant population. Assays of cytochrome P450
      activity (4-CNMA demethylation and aldrin epoxidation) did not identify elevated
      activity in resistant 3rd instars. Granular soil insecticides were applied at
      planting to corn, Zea mays L., in replicated field trials in 1997 and 1998 at the
      same Phelps County site as the source of resistant rootworms for the laboratory
      studies. In 1997, planting time applications of Counter 20CR, Counter 15 G
      (terbufos), and Lorsban 15 G (chlorpyrifos) resulted in the lowest root injury
      ratings (1-6 Iowa scale); 2.50, 2.55, 2.65, respectively (untreated check root
      rating of 4.55). In 1998, all insecticides performed similarly against a lower
      rootworm density (untreated check root rating of 3.72). These studies suggest
      that resistance previously documented in adults also is present in 3rd instars,
      esterases are possibly involved as resistance mechanisms, and resistance to
      methyl parathion in adults is also evident in larvae, but does not confer cross
      resistance in larvae to all organophosphate insecticides.

PMID- 14658505
TI  - Heritability of tolerance to the Cry1Ab toxin of Bacillus thuringiensis in Chilo
      suppressalis (Lepidoptera: Crambidae).
AB  - Heritability of Chilo suppressalis (Walker) tolerance to the Cry1Ab toxin of
      Bacillus thuringiensis Berliner was estimated using a half-sibling design.
      Artificial diet with and without Cry1Ab was infested with progenies of 20 males,
      each mated with 2 females, and mortality was scored 5 d after infestation. The
      progeny of each female was reared and scored separately. Mean mortality of the 20
      families on the Cry1Ab diet was 46.5%. The effects of both male parent and of
      female parent within male parent were significant. Heritability was estimated to
      be 0.52, suggesting that a high proportion of phenotypic variation was because of
      genetic differences. Mortality on the Cry1Ab diet was not correlated with
      mortality on control diet, indicating that differences among families in
      tolerance to Cry1Ab were not attributable to differences in general fitness. Our
      results indicate that "high dose" Bt rice plants may be particularly important
      for Cry1Ab resistance management in C. suppressalis populations.

PMID- 14658506
TI  - Cross-resistance to alpha-cypermethrin after xanthotoxin ingestion in Helicoverpa
      zea (Lepidoptera: Noctuidae).
AB  - Cytochrome P450 monooxygenases (P450) are membrane-bound hemoproteins that play
      important roles in conferring protection against both naturally occurring
      phytochemicals and synthetic organic insecticides. Despite the potential for
      common modes of detoxification, cross-resistance between phytochemicals and
      synthetic organic insecticides has rarely been documented. In this study, we
      examined the responses of a susceptible strain of corn earworm, Helicoverpa zea
      (Boddie), a polyphagous noctuid, to exposure by an allelochemical infrequently
      encountered in its host plants and by an insecticide widely used for control
      purposes. Within a single generation, survivors of xanthotoxin exposure displayed
      higher levels of tolerance to alpha-cypermethrin than did unexposed control
      larvae. The F1 offspring of xanthotoxin-exposed survivors also displayed higher
      alpha-cypermethrin tolerance than did offspring of unexposed control larvae,
      suggesting that increased alpha-cypermethrin tolerance after xanthotoxin exposure
      represents, at least in part, heritable resistance. Administration of piperonyl
      butoxide, a P450 synergist, demonstrated that resistance to both xanthotoxin and
      alpha-cypermethrin is P450-mediated. Alpha-cypermethrin-exposed survivors,
      however, failed to show superior growth on xanthotoxin diets. Assays with control
      larvae, larvae induced by both xanthotoxin and alpha-cypermethrin, and survivors
      of LD50 doses of both compounds indicated that H. zea midgut P450s are capable of
      metabolizing both xanthotoxin and alpha-cypermethrin. Metabolism of each compound
      is significantly inhibited by the presence of the other compound, suggesting that
      at least one form of P450 in H. zea midguts degrades both compounds and may
      constitute the biochemical basis for possible cross-resistance. Compared with
      control larvae, xanthotoxin- and alpha-cypermethrin-induced larvae displayed 2-
      to 4-fold higher P450-mediated metabolism of both compounds. However, xanthotoxin
      and alpha-cypermethrin-exposed survivors exhibited much higher (2.5- to 11-fold)
      metabolism of both compounds than did the induced larvae. The metabolism results,
      like the bioassay results, are consistent with the interpretation that increased
      alpha-cypermethrin tolerance after xanthotoxin exposure is attributable mainly to
      heritable resistance.

PMID- 14658507
TI  - Frequency of resistance to Bacillus thuringiensis toxin Cry1Ab in an Iowa
      population of European corn borer (Lepidoptera: Crambidae).
AB  - The refuge plus high-dose strategy for resistance management assumes that the
      frequency of resistance alleles is low. We used an F2 screen to estimate the
      frequency of resistance to transgenic corn that produces Bacillus thuringiensis
      Berliner Cry1Ab toxin (Bt corn) in an Iowa population of European corn borer,
      Ostrinia nubilalis (Hubner). We also proposed a modification to the statistical
      analysis of the F2 screen that extends its application for nonuniform prior
      distributions and for repeated sampling of a single population. Based on a sample
      of 188 isofemale lines derived from females caught at light traps during the 2nd
      flight of 1997, we show with 95% confidence that the frequency of resistance to
      Bt corn was <3.9 x 10(-3) in this Iowa population. These results provide weak
      evidence that the refuge plus high-dose strategy may be effective for managing
      resistance in O. nubilalis to Bt corn. Partial resistance to Cry1Ab toxin was
      found commonly. The 95% CI for the frequency of partial resistance were [8.2 x
      10(-4), 9.4 x 10(-3)] for the Iowa population. Variable costs of the method were
      14.90 dollars per isofemale line, which was a reduction of 25% compared with our
      initial estimate.

PMID- 14658508
TI  - Alterations in esterases are associated with malathion resistance in Habrobracon
      hebetor (Hymenoptera: Braconidae).
AB  - Biochemical mechanisms of malathion resistance were investigated in a malathion
      resistant strain of the parasitoid Habrobracon hebetor Say collected from a farm
      storage in Kansas. General esterase activities were significantly lower in the
      resistant strain compared with those in a susceptible strain. However, no
      significant differences were found in activities of malathion specific
      carboxylesterase (MCE), glutathione S-transferase and cytochrome P450 dependent O
      demethylase activities, cytochrome P450 contents, and sensitivity of
      acetylcholinesterase to inhibition by malaoxon between the 2 strains. Because MCE
      was not elevated in the resistant strain, the weak malathion resistance in H.
      hebetor may result from a different mechanism compared with that hypothesized for
      some insect species in which reduced general esterase activity is accompanied by
      an elevated MCE. Decreased esterase activity in the resistant strain suggested
      that null alleles of some esterases were associated with the resistance. Indeed,
      E1 and E2, major esterases in the susceptible strain, were not present in the
      resistant strain on polyacrylamide gels that were stained for esterase activity
      using the model substrate 1-naphthyl acetate. In contrast, the activity of
      esterase E3 on the gels was much higher in the resistant strain as compared with
      that of the susceptible strain. These findings indicate that malathion resistance
      in H. hebetor is associated with both an increased activity of the esterase E3
      and null alleles of the esterases E1 and E2.

PMID- 14658509
TI  - Efficacy of imidacloprid for control of cereal leaf beetle (Coleoptera:
      Chrysomelidae) in barley.
AB  - The toxicity of imidacloprid to the cereal leaf beetle, Oulema melanopus (L.),
      was measured under laboratory and field conditions. Insect mortality and plant
      damage were determined from artificial and natural infestations of O. melanopus
      applied to various growth stages of barley. All rates of imidacloprid formulated
      and applied as a seed treatment caused >90% mortality to cereal leaf beetle
      larvae when barley was infested with eggs at the 4-leaf stage, but were
      ineffective when barley was infested with eggs at the early tillering or flag
      leaf stages of barley. This window of susceptibility influenced results obtained
      in field trials where peak larval emergence did not occur until the early
      tillering stage of barley. The resulting mortality in plants from treated seeds
      never exceeded 40% in the field. Foliar imidacloprid, however, caused >90%
      mortality in the field, and may be another option in the management of the cereal
      leaf beetle.

PMID- 14658510
TI  - Repellency and toxicity of oil from Artemisia annua to certain stored-product
      beetles.
AB  - The essential oil of Artemisia annua L. was tested for its toxic repellent and
      development inhibitory activities against 2 economically important stored product
      insects: Tribolium castaneum (Herbst) and Callosobruchus maculatus (L.). Adult
      beetles of T. castaneum were repelled significantly by oil of A. annua at 1%
      concentration (vol:vol) and above in filter paper arena test. Dose-response
      relationship of A. annua oil revealed a significant negative correlation between
      larval survival; pupal survival and adult emergence of T. castaneum (i.e.,
      increase in dose caused decrease in survival and adult emergence). Effective
      concentration (EC50) to reduce F1 progeny by 50% was calculated to be 2.6 and 4.1
      microl/ml solvent against both the insect species, C. maculatus and T. castaneum,
      respectively. The relationship between bioactivity of oil from A. annua and
      responses of T. castaneum and C. maculatus is discussed. We found that oil from
      A. annua was largely responsible for both repellent (behavioral) and toxic
      (physiological) actions on 2 species of insect tested.

PMID- 14658511
TI  - Interaction between halofenozide and the entomopathogenic nematode
      Heterorhabditis marelatus for control of Japanese beetle (Coleoptera:
      Scarabaeidae) larvae.
AB  - Japanese beetle, Popillia japonica Newman is a major pest of turf and
      ornamentals. Laboratory bioassays were conducted to evaluate the potential
      interactions between a biological control agent, Heterorhabditis marelatus
      (Nematoda: Heterorhabditidae) IN strain and the insecticide halofenozide against
      both overwintered and nonoverwintered 3rd instars of Japanese beetle. Treatments
      consisted of all combinations of 2 rates of halofenozid with H. marelatus
      nematodes Imidacloprid was used as a standard. Percentage larval mortality was
      evaluated at 7, 14, and 21 d after treatment. No deleterious effects were
      observed. The nematode treatments generally produced significantly greater larval
      mortality relative to both chemical treatments. Twenty-one days after treatment,
      both rates of nematodes resulted in 100% mortality, whereas insecticide
      treatments did not surpass 60% mortality. No synergism was detected in any of the
      combination treatments. There were no significant differences in nematode
      reproduction in larvae exposed to halofenozide and nematodes versus larvae
      exposed to only nematodes.

PMID- 14658512
TI  - Laboratory and field evaluation of Beauveria bassiana against sugarcane
      stalkborers (Lepidoptera: Pyralidae) in the lower Rio Grande Valley of Texas.
AB  - Of approximately 18,200 ha planted to sugarcane in south Texas, only
      approximately 80 ha (<0.5%) are treated with insecticides because this type of
      control is widely regarded as ineffective against stalkboring pyralids, the key
      pests of sugarcane. Therefore, nonchemical control measures, such as resistant
      varieties and biological controls, must be evaluated to mitigate the losses
      caused by stalkborers. We performed laboratory and field evaluations on the use
      of Beauveria bassiana (Balsamo) Vuillemin (Deuteromycotina: Hyphomycetes) (strain
      GHA) against the Mexican rice borer, Eoreuma loftini (Dyar) (Lepidoptera:
      Pyralidae), which causes damage in south Texas estimated at between 10 and 20
      million dollars annually. We also performed bioassays against the sugarcane
      borer, Diatraea saccharalis (F.) (Pyralidae), the key pest in other sugarcane
      growing areas. In the bioassays, E. loftini was substantially more susceptible to
      B. bassiana than D. saccharalis, based on both 5-d LD50 values and survival
      times. A commercial oil-based formulation of B. bassiana was evaluated in the
      field using the following treatments: oil alone (control), B. bassiana + oil, and
      B. bassiana + Silwet L-77 carrier at an application rate of 5 x 10(13) spores per
      hectare. Neither numbers of E. loftini per stalk, nor stalk damage (approximately
      20% bored internodes) were significantly affected by treatment. The application
      of B. bassiana + Silwet significantly affected the numbers of internodes showing
      high damage, but not those with low or medium damage. Analysis of yield data and
      juice quality showed no significant treatment effects. We conclude that the
      application of Beauveria + Silwet offers the best chances for reducing damage
      caused by E. loftini of those treatments tested. However, reductions in insect
      incidence or damage did not result in measurable increases in yield or sugar
      quality, probably because of insufficient coverage. Effective control of
      stalkboring pyralids in sugarcane using B. bassiana will likely require
      improvements in delivery technology.

PMID- 14658513
TI  - In vivo study on combined toxicity of Metarhizium anisopliae (Deuteromycotina:
      Hyphomycetes) strain ESC-1 with sublethal doses of chlorpyrifos, propetamphos,
      and cyfluthrin against German cockroach (Dictyoptera: Blattellidae).
AB  - The effect of Metarhizium anisopliae (Metschnikoff) Sorokin strain ESC-1 alone
      and in combination with sublethal doses of commercial formulations of
      chlorpyrifos, propetamphos and cyfluthrin on mortality of CSMA strain of German
      cockroach, Blattella germanica (L.), was determined by conducting in vivo studies
      that included 3 bioassays. Spores of M. anisopliae cultured on SDAY media had
      germination of >90%. Based on bioassay 1, doses ranging from 0.5 to 300 ppm of
      chlorpyrifos and propetamphos, and 0.05 to 40 ppm of cyfluthrin were selected for
      bioassays 2 and 3. Cockroach mortality ranged from 5 to 20% for insecticides
      alone and 48 to 70% for insecticides + M. anisopliae in bioassay 2. In bioassay
      3, mortality ranged from 15 to 60% for insecticides and 57.5 to 92.5% for
      insecticides + M. anisopliae. Percentage of cockroach mortality resulting from
      insecticide + M. anisopliae combinations was significantly higher than
      insecticide alone. Mortality was also significantly higher in certain insecticide
      + M. anisopliae combinations than M. anisopliae alone. There was no significant
      interaction between M. anisopliae and insecticides with their concentrations in
      bioassay 2, indicating an additive effect. But in bioassay 3, a significant
      interaction was observed when M. anisopliae was combined with multiple
      insecticide concentrations. The interaction indicated an additive effect for
      chlorpyrifos and cyfluthrin, and a synergistic effect for propetamphos. There
      were significant differences in LT50 among various treatment combinations. M.
      anisopliae alone or insecticide + M. anisopliae combinations did not affect body
      weight in treated German cockroaches.

PMID- 14658514
TI  - Biological control agents for white grubs (Coleoptera: Scarabaeidae) in
      anticipation of the establishment of the Japanese beetle in California.
AB  - We tested biological control agents for the control of 3rd-instar scarab
      turfgrass pests, both for the masked chafer Cyclocephala hirta LeConte and the
      Japanese beetle, Popillia japonica Newman. The former species is endemic in
      California whereas the latter, although not yet established, constitutes a
      permanent serious threat to agriculture and horticulture in California. We
      conducted experiments using C. hirta in California and P. japonica in New Jersey.
      A field trial conducted in 2 different California turfgrass sites compared the
      field persistence in the absence of hosts of Bacillus thuringiensis Berliner
      subspecies japonensis Buibui strain, the milky disease bacterium, Paenibacillus
      (=Bacillus) popilliae (Dutky), and the entomopathogenic nematodes Steinernema
      kushidai Mamiya and Heterorhabditis bacteriophora Poinar to that of the
      organophosphate diazinon. Soil samples taken 0-70 d after applications were bio
      assayed with P. japonica. Only diazinon and the entomopathogenic nematode S.
      kushidai caused substantial mortality and S. kushidai activity persisted
      significantly longer than diazinon activity. In greenhouse experiments,
      combinations of entomopathogenic nematode species usually resulted in additive
      mortality of scarab larvae. Combinations of S. kushidai and diazinon also
      resulted in additive mortality. In field trials, the efficacy of H. bacteriophora
      and especially S. kushidai and S. glaseri, was comparable to that of diazinon
      over 14-18 d. However, it is likely that at least S. kushidai would have
      outperformed diazinon over an extended period because of its longer persistence
      and potential for recycling in the hosts. S. kushidai, should it become
      commercially available, deserves further examination as an alternative to
      chemical white grub control especially as a highly compatible component of
      sustainable turfgrass management.

PMID- 14658515
TI  - Methyl eugenol and cue-lure traps for suppression of male oriental fruit flies
      and melon flies (Diptera: Tephritidae) in Hawaii: effects of lure mixtures and
      weathering.
AB  - Methyl eugenol (4-allyl-1,2-dimethoxybenzene-carboxylate) and cue-lure [4-(p
      acetoxyphenyl)-2-butanone] are highly attractive kairomone lures to oriental
      fruit fly, Bactrocera dorsalis (Hendel), and melon fly, B. cucurbitae
      (Coquillett), respectively. Plastic bucket traps were evaluated as dispensers for
      methyl eugenol and cue-lure for suppression of the 2 fruit flies in Hawaii.
      Methyl eugenol and cue-lure mixtures were compared with pure methyl eugenol or
      cue-lure over 4 seasons. B. dorsalis captures differed significantly with
      treatment and season. B. dorsalis captures with 100% methyl-eugenol were
      significantly greater than all other treatments (25, 50, and 75%). B. cucurbitae
      captures also differed significantly with treatment but not with season. Captures
      with 100, 75, and 50% cue-lure were not significantly different. Bucket traps
      baited with cue-lure (+ malathion) and weathered under Hawaiian climatic
      conditions were attractive to B. cucurbitae up to 8 wk. Two methyl eugenol
      dispensers (canec disks and Min-U-Gel) were compared with bucket traps.
      Dispensers (methyl eugenol + malathion) were weathered for 2-16 wk under Hawaiian
      climatic conditions and bioassayed during summer and winter. Initially, captures
      of B. dorsalis were not significantly different for the 3 dispensers. Bucket
      traps and canec disks were most resistant to weather, remaining attractive to B.
      dorsalis flies up to 16 wk. Min-U-Gel was least resistant, losing attractiveness
      to B. dorsalis flies within 2 wk. On the basis of performance, bucket traps and
      canec disks were equally long-lived up to 14 wk; thereafter, bucket traps were
      slightly more attractive during winter. Canec disks were cheapest, but on the
      basis of possible environmental concerns, bucket traps may be the best all-around
      choice for areawide suppression of fruit flies.

PMID- 14658516
TI  - Effects of temperature on the flight activity of Graphocephala atropunctata
      (Hemiptera: Cicadellidae).
AB  - Graphocephala atropunctata (Signoret) is the principal vector of Xylella
      fastidiosa (Wells, Raju, Hung, Weisberg, Mandelco-Paul and Brenner), the
      bacterium that causes Pierce's disease of grapevine in coastal California.
      Monitoring the activity of C. atropunctata in the early spring is important for
      timing insecticide sprays and assessing the potential for disease spread to
      adjacent vineyards. Trapping studies with yellow sticky traps over 3 yr in Napa
      Valley, CA, established a significant correlation between early spring trap catch
      and temperature. Sticky trap catches of G. atropunctata occurred in the springs
      of 1996-1998 only when temperature was greater than or equal to 14.5 degrees C.
      In 1997 and 1998, the degree-hours (> 14.5 degrees C) per day from sunrise to
      sunset during March and April, but not in May, correlated significantly with trap
      catches. The temperature threshold of 14.5 degrees C in the early spring can be
      used to improve the timing of insecticidal applications aimed at reducing C.
      atropunctata populations in vineyards affected by Pierce's disease.

PMID- 14658517
TI  - Volatile host fruit odors as attractants for the oriental fruit fly (Diptera:
      Tephritidae).
AB  - We examined the responses of oriental fruit flies, Bactrocera dorsalis Hendel, to
      the odors of different stages and types of fruit presented on potted trees in a
      field cage. Females were most attracted to odors of soft, ripe fruit. Odors of
      common guava were more attractive to females than papaya and starfruit, and
      equally as attractive as strawberry guava, orange, and mango. In field tests,
      McPhail traps baited with mango, common guava, and orange captured equal numbers
      of females. Traps baited with mango were compared with 2 commercially available
      fruit fly traps. McPhail traps baited with mango captured more females than
      visual fruit-mimicking sticky traps (Ladd traps) and equal numbers of females as
      McPhail traps baited with protein odors. Results from this study indicate that
      host fruit volatiles could be used as lures for capturing oriental fruit flies in
      orchards.

PMID- 14658518
TI  - New chemical attractants for trapping Lacanobia subjuncta, Mamestra configurata,
      and Xestia c-nigrum (Lepidoptera: Noctuidae).
AB  - Significant numbers of 3 pest species of noctuid moths were captured in traps
      baited with acetic acid, 3-methyl-1-butanol, and 3-methyl-1-pentanol. These were
      Lacanobia subjuncta (Grote & Robinson); Mamestra configurata Walker, bertha
      armyworm; and Xestia c-nigrum (L.), spotted cutworm. The combination of acetic
      acid and 3-methyl-1-butanol was superior to the individual chemicals in
      attracting all 3 species, whereas the combination of acetic acid and 3-methyl-1
      pentanol was superior to the individual chemicals in attracting X. c-nigrum. For
      the 3 species of moths, numbers captured were similar in traps baited with the
      combination of acetic acid and 3-methyl-1-butanol or acetic acid and 3-methyl-1
      pentanol. Traps baited with these attractants captured both males and females at
      a ratio near 1:1.

PMID- 14658519
TI  - Novel extraction of German cockroach (Dictyoptera: Blattellidae) fecal pellets
      enhances efficacy of spray formulation insecticides.
AB  - Methanol extracts of German cockroach, Blattella germanica (L.), fecal pellets
      have limited use as pheromone attractants in the urban environment because of
      their unpleasant color and odor. To eliminate these characteristics, a novel
      aqueous extract of German cockroach feces was formulated. Fetal material was
      extracted with methylene chloride and mixed with water. The aqueous phase of the
      extract was colorless and relatively odorless compared with methanol fecal
      extracts. Aqueous extract was bioassayed and compared with methanol extracts for
      aggregation activity. The efficacy of chlorpyrifos and boric acid formulations
      was tested with and without the addition of fecal extracts. In tests with
      chlorpyrifos, the addition of the aqueous extract produced significantly greater
      mortality in young nymphs than either chlorpyrifos alone or chlorpyrifos +
      methanol extract. There were no differences in mortality between the 2 extract +
      boric acid treatments during the test period, and both enhanced mortality.

PMID- 14658520
TI  - Laboratory and field performance of an imidacloprid gel bait against German
      cockroaches (Dictyoptera: Blattellidae).
AB  - An experimental 2.15% imidacloprid gel bait containing approximately 44% water
      was evaluated in laboratory and field studies against the German cockroach,
      Blattella germanica (L). In continuous exposure tests, toxicity and presumably
      bait consumption varied with cockroach stage, deprivation of competitive food,
      and temperature. The LT50 values for cockroaches provided with competitive food
      ranged from approximately 0.9 h for adult females to 190 h for small nymphs. The
      LT50s for cockroaches not provided competitive food ranged from approximately 1.7
      h for adult females to approximately 31 h for adult males. The LT50s decreased
      exponentially with temperature between 10 and 30 degrees C. Even though the bait
      was significantly more repellent (approximately 38%) than an untreated control
      (approximately 14%) when tested in Ebeling choice boxes, performance index values
      were positive and increased to nearly 100 (indicating high mortality and low
      repellency) after 14 d. When applied at 15-45 g per kitchen, the bait
      significantly reduced German cockroach trap catch in infested homes during a 4-wk
      period. There was a approximately 50% reduction after 1 wk and approximately 80%
      reduction 4 wk after treatment.

PMID- 14658521
TI  - Argentine ant (Hymenoptera: Formicidae) trail pheromone enhances consumption of
      liquid sucrose solution.
AB  - We investigated whether the Argentine ant, Linepithema humile (Mayr), trail
      pheromone, Z9-16:Ald, could enhance recruitment to and consumption of liquid
      sucrose solutions. All tests were done as paired comparisons with a 10% sucrose
      solution as food. In the laboratory, mixing 20 microl of a 10-microg/ml solution
      of the pheromone with 50 microl of the 10% sucrose solution increased the number
      of ants feeding by >150%. In a field test, we combined the trail pheromone with a
      10% sucrose solution in 50-ml vials. These vials were covered with a plastic
      membrane that has 1.5-mm-diameter holes punched uniformly across its surface.
      Ants could drink from the holes after the vials were inverted. For half of the
      vials, 1 microg of the pheromone was put onto the plastic membrane before the
      vials were filled with a 10% sucrose solution. The remaining vials had no
      pheromone on the plastic membrane. After 4 h we measured the consumption in each
      vial. Bait consumption with the pheromone was enhanced by 29%. In a 2nd series of
      tests, vials were left outside for 24 h. The consumption rate was 33% higher with
      the pheromone compared with the controls that didn't have pheromone.

PMID- 14658522
TI  - Glossina austeni (Diptera: Glossinidae) eradicated on the island of Unguja,
      Zanzibar, using the sterile insect technique.
AB  - An area-wide integrated tsetse eradication project was initiated in Zanzibar in
      1994 by the International Atomic Energy Agency and the governments of Tanzania
      and Zanzibar, to eradicate Glossina austeni Newstead from Unguja Island
      (Zanzibar) using the sterile insect technique. Suppression of the tsetse
      population on Unguja was initiated in 1988 by applying residual pyrethroids as a
      pour-on formulation to livestock and by the deployment of insecticide impregnated
      screens in some of the forested areas. This was followed by sequential releases
      of gamma-sterilized male flies by light aircraft. The flies, packaged in carton
      release containers, were dispersed twice a week along specific flight lines
      separated by a distance of 1-2 km. More than 8.5 million sterile male flies were
      released by air from August 1994 to December 1997. A sterile to indigenous male
      ratio of >50:1 was obtained in mid-1995 and it increased to >100:1 by the end of
      1995. As a consequence the proportion of sampled young females (1-2 ovulations),
      with an egg in utero in embryonic arrest or an uterus empty as a result of
      expulsion of a dead embryo, increased from <25% in the 1st quarter to >70% in the
      last quarter of 1995. In addition, the age structure of the female population
      became significantly distorted in favor of old flies (> or = 4 ovulations) by the
      end of 1995. The apparent density of the indigenous fly population declined
      rapidly in the last quarter of 1995, followed by a population crash in the
      beginning of 1996. The last trapped indigenous male and female flies were found
      in weeks 32 and 36, 1996, respectively. Time for 6 fly generations elapsed
      between the last catch of an indigenous fly and the end of the sterile male
      releases in December 1997.

PMID- 14658523
TI  - Yield response of pumpkin and winter squash to simulated cucumber beetle
      (Coleoptera: Chrysomelidae) feeding injury.
AB  - Field studies were conducted to characterize the yield responses of pumpkin,
      Cucurbita pepo L., and wintersquash, Cucurbita maxima Duch., to simulated striped
      cucumber beetle, Acalymma vittatum (F.), feeding damage. Preliminary studies in
      pumpkin ('Spookie') were conducted in 1993, and more complete studies in 1994 and
      1995 in pumpkin (Spookie), and in 1995 and 1996 in winter squash ('Waltham').
      Plants were artificially injured 1 time at the cotyledon, 1st, 2nd, or 3rd true
      leaf stages by clipping specified percentages of leaf area from all leaves on the
      plant. Treatments consisted of a control treatment with no simulated injury and 4
      levels of simulated injury. Pumpkin treatments were 10, 20, 40, and 80% leaf area
      removal in 1993 and 1994 and 20, 40, 60, and 80% in 1995. Winter squash
      treatments were 20, 40, 60, and 80% leaf area removal in 1995, and 10, 20, 40,
      and 80% in 1996. In 1993, 5 wk after planting, mean leaf, stem, and total dry
      weight were significantly lower on pumpkin plants subjected to > or = 20%
      simulated leaf injury regardless of the growth stage when the injury occurred.
      Injury at the 3rd leaf stage resulted in a significant reduction in the mean leaf
      and total dry weight of plant, across all levels of injury. At 2-3 wk before crop
      maturity, fruit weight and number of fruit per plant were significantly lower
      with 80% leaf area removal. In 1994 and 1995, and when pumpkins were grown to
      full maturity and apparently able to compensate for the simulated damage, neither
      number nor weight of marketable fruit per plant were affected significantly by
      simulated injury at any stage of development nor level of simulated injury. In
      contrast, > or = 20% and 80% leaf area removal to winter squash resulted in
      significant reductions in the weight of marketable fruit and/or number of
      marketable fruit, in 1995 and 1996, respectively. The results of this study
      indicate that pumpkins can tolerate relatively high levels of simulated
      defoliation, whereas winter squash is less tolerant. Variable results across
      years in winter squash may indicate an interaction between injury and plant
      stress caused by abiotic factors such as soil moisture availability.

PMID- 14658524
TI  - Evaluating grower, landscape manager, and consumer perceptions of azalea lace bug
      (Heteroptera: Tingidae) feeding injury.
AB  - A survey using modified azalea stems was used to establish a "tally threshold
      value" for assessing azalea lace bug, Stephanitis pyrioides (Scott), feeding
      injury to azalea shrubs. Consumers and green-industry professionals, represented
      by ornamental growers, landscape architects, and landscape managers, recognized
      azalea lace bug injury when injured leaf area exceeded 2%. Purchase and treatment
      decisions of professionals and consumers were evaluated by surveying responses to
      Rhododendron indica variety alba 'Delaware Valley White' azaleas representing a
      range of damage. Survey participants also provided a brief biographical
      background and answers to questions regarding pesticide use, ability to identify
      diseases, pests, and beneficial organisms, and willingness to consider pesticide
      alternatives. Professionals and consumers expressed a strong interest in limiting
      urban pesticide use. The 2 groups indicated a hypothetically acceptable level of
      6-10% plant damage by arthropod pests. A 2% injury threshold was used to
      determine the level of proportional damage (the percentage of leaves displaying
      2% or more lace bug leaf feeding injury) resulting in either the rejection of
      plant purchase or initiation of treatment. A nonlinear curve was fit to treatment
      and no-purchase responses of professionals and consumers using a modified 3
      parameter Mitscherlich nonlinear growth function. Half of the surveyed
      professionals and consumers indicated that damage proportions >10% (1.03% actual
      injury) were sufficient to reject an azalea for purchase. Proportional damage
      levels >43% (3.3% actual injury) would be necessary to prompt 50% of the
      respondents to initiate treatment of damaged azaleas to control lace bugs.

PMID- 14658525
TI  - Colorado potato beetle (Coleoptera: Chrysomelidae) feeding, development, and
      survival to adulthood after continuous exposure to Bacillus thuringiensis subsp.
      tenebrionis-treated potato foliage from the field.
AB  - Colorado potato beetle, Leptinotarsa decemlineata (Say), feeding, development,
      and survival to adulthood were examined after continuously exposing large larvae
      to Bacillus thuringiensis subsp. tenebrionis-treated potato foliage from the
      field. In laboratory assays, the overall consumption and the length of period to
      become prepupae were determined for larvae, which began as 3rd and 4th instars,
      that were offered potato leaf disks with naturally declining levels of B.
      thuringiensis residue. In small-cage field experiments, survival to adulthood and
      the period to adult emergence for beetles confined to potato plants treated with
      B. thuringiensis beginning as 3rd and 4th instars also were examined. Third
      instars remaining on plants after a B. thuringiensis application were unlikely to
      feed and 4th instars consumed only approximately 50% as much foliage as those fed
      untreated foliage. Many late instars subjected to B. thuringiensis-treated
      foliage failed to survive to adulthood; 58-83% of these beetles died during the
      larval stage. Reduced feeding and poor survival of late instars suggest that
      counts of large larvae after application do not provide a complete picture of the
      efficacy of the B. thuringiensis treatment. Late instar Colorado potato beetles
      that were exposed continually to naturally declining levels of B. thuringiensis
      treated potato foliage took an average of 1.8-4.5 d longer to become prepupae and
      4-8 d longer to emerge as adults compared with those provided with untreated
      foliage. Delayed emergence of adults that fed on B. thuringiensis-treated
      potatoes as late instars indicated that development was prolonged in these
      insects because of ingestion of a sublethal dose of B. thuringiensis.

PMID- 14658526
TI  - Effect of specific and generic sex attractant blends on pheromone trap captures
      of four leafroller species in mid-Atlantic apple orchards.
AB  - The responses of tufted apple bud moth, Platynota idaeusalis (Walker), the
      leafroller P. flavedana Clemens, redbanded leafroller, Argyrotaenia velutinana
      (Walker), and obliquebanded leafroller, Choristoneura rosaceana (Harris), to the
      pheromone blends of each, as well as to 3 putative generic blends (two- and three
      component blends containing pheromone elements of each of the 4 species) were
      evaluated in small orchard plots. P. idaeusalis and P. flavedana, and A.
      velutinana and C. rosaceana comprise 2 pairs of species, each pair with broad
      overlap in pheromone blend, and quite different from one another. Each generic
      blend suppressed trap captures of all 4 species. The blends for P. idaeusalis and
      P. flavedana each reduced captures for these species. Furthermore, the blend for
      P. idaeusalis also suppressed captures of A. velutinana. The P. flavedana blend
      did not reduce captures of A. velutinana; in fact, at times captures increased.
      This study determines relative abilities of several sex attractant blends to
      reduce captures of 4 leafroller species in pheromone traps, presumably reflecting
      the ability of a blend to reduce orientation of males to females in a large block
      situation. This is a requisite 1st step in the development of a multispecies
      mating disruption blend.

PMID- 14658527
TI  - Impact of whole-canopy and systemic insecticidal treatments on Callirhytis
      cornigera (Hymenoptera: Cynipidae) and associated parasitoids on pin oak.
AB  - The gall wasp Callirhytis cornigera (Osten Sacken) is a cynipid with alternating
      generations that produce large, woody stem galls and tiny blister-like leaf galls
      on pin oak, Quercus palustris Muenchhausen, in the United States. We tested 3
      approaches to control the leaf-galling generation, and determined their impact on
      associated parasitoids and effectiveness in reducing numbers of new stem galls.
      First, trees were sprayed with bifenthrin or chlorpyrifos in late March to kill
      females emerging from stem galls before they oviposited into buds. Second,
      concentrated solutions of abamectin, imidacloprid, or bidrin were injected from
      pressurized containers into tree sapwood to control larvae developing in young
      leaf galls. Finally, systemic insecticides (acephate, abamectin, dimethoate, or
      imidacloprid) were sprayed at early leaf expansion (2 May) or to young, expanded
      leaves (17 May) to target larvae in leaf galls. Parasitoids, mostly eulophids,
      accounted for approximately 70% mortality of leaf-galling C. cornigera larvae on
      untreated trees. Whole-canopy sprays during C. cornigera emergence from stem
      galls reduced overall numbers of galled leaves and leaf galls. Trunk injections
      of bidrin or abamectin resulted in significant mortality of gall inhabitants,
      including parasitoids. However, neither of the aforementioned approaches
      significantly reduced numbers of new stem galls. Sprays of abamectin, dimethoate,
      or imidacloprid applied on 2 May caused high mortality of all gall inhabitants.
      There was no net benefit, however, because parasitism caused a similar reduction
      in C. cornigera survival on unsprayed shoots. Sprays applied later in leaf
      expansion had little impact on gall inhabitants. Of the treatments tested,
      bifenthrin sprays at bud break provided the greatest reduction in new leaf galls,
      whereas bidrin injections provided the greatest reduction in gall wasps emerging
      from galled leaves. This study suggests that gall wasp outbreaks are unlikely to
      be controlled by a single treatment, regardless of application method.

PMID- 14658528
TI  - Why do surgeons love to hate stents?

PMID- 14658529
TI  - Does preoperative biliary stenting affect the outcome of pancreatico
      duodenectomy?
AB  - BACKGROUND: Controversy exists whether preoperative endoscopic biliary stenting
      to reduce serum bilirubin level affects the outcome of pancreaticoduodenectomy.
      AIM: To determine whether preoperative endoscopic biliary stenting is associated
      with altered morbidity or mortality after pancreaticoduodenectomy. METHODS: In 37
      consecutive patients with periampullary lesion undergoing pancreaticoduodenectomy
      over a 6-year period, frequency of septic complications, occurrence of pancreatic
      leak or bleeding, duration of hospital stay, and mortality were studied; of
      these, 15 had preoperative biliary stenting and 22 had not. RESULTS:
      Postoperative infective complications occurred more often in the patients with
      biliary stent than in those without (26% vs 0%, p=0.04). Postoperative recovery
      time, hospital stay and mortality were similar in the two groups. CONCLUSION:
      Preoperative biliary stenting is associated with septic complications, but this
      does not affect postoperative recovery after pancreaticoduodenectomy.

PMID- 14658530
TI  - Morphological changes in bile ducts following preoperative biliary stenting.
AB  - OBJECTIVES: To analyze the morphological changes in bile ducts following
      endobiliary stent insertion, and consequent technical problems encountered at
      surgery. METHODS: Data on bile duct morphology--gross (luminal diameter and wall
      thickness) and microscopic (histological changes in bile duct wall graded
      semiquantitatively)--and operative parameters related to bile duct dissection
      (grade of difficulty in dissection) were collected prospectively in 31
      consecutive patients undergoing pancreatico-duodenectomy. These data were
      compared between patients who had undergone preoperative endoscopic biliary stent
      placement (n=17) and those who had not (n=14). RESULTS: Mean duration of stenting
      before surgery was 34 (range 10-120) days. Stented ducts were significantly
      narrower (luminal diameter 9 [7-12] mm vs. 17.5 [8-23] mm; p=0.0001) and had
      thicker walls (2.3 [1.3-3.5] mm vs. 1.85 [0.8-2.2] mm; p=0.004) compared to non
      stented ones. On microscopy, stented ducts had advanced grades of submucosal
      gland hypertrophy, fibrosis and inflammatory cell infiltrate. Difficulty in bile
      duct dissection was encountered more often in patients who had been stented than
      in those without stents, though the difference was not statistically significant.
      CONCLUSION: Endobiliary stent placement results in significant morphological and
      fibroproliferative inflammatory changes in bile ducts, making dissection
      difficult.

PMID- 14658531
TI  - Incidence of cancer esophagus in Quetta and Karachi, Pakistan.
AB  - OBJECTIVE: To study the differences in the incidence of cancer esophagus in
      Karachi and Quetta, Pakistan. METHODS: Incident cases of cancer esophagus
      registered from January 1, 1995 to December 31, 2000 were included for Karachi
      South, and those registered from January 1, 1998 to December 31, 2000 were
      included for Karachi Division and Quetta. RESULTS: In Quetta, cancer esophagus
      had age-standardized incidence rate (ASIR) of 25.5/100,000 population in males
      and 23.4/100,000 population in females, and it was the commonest malignancy in
      both genders. In comparison, in Karachi South and Karachi Division, cancer
      esophagus ranked 7th among cancers in males (ASIR 6.2/100,000 and 5.0/100,000
      population, respectively) and 5th in females (7.0/100,000 and 4.9/100,000
      population, respectively). The ASIR was similar among males and females in all
      data sets. CONCLUSION: The incidence of cancer esophagus in Quetta is comparable
      to that in high-incidence regions, whereas the incidence in Karachi is similar to
      that in moderate-incidence zones. In contrast to other world regions, cancer
      esophagus was equally common in males and females in Pakistan. The high risk in
      Quetta warrants investigation for risk factors and a targeted cancer control
      program.

PMID- 14658532
TI  - Transjugular liver biopsy--experience in fifty patients.
AB  - OBJECTIVE: We evaluated the safety, adequacy, clinical impact and cost of
      transjugular liver biopsies performed at our institution. METHODS: Eighty-four
      biopsies performed in 50 consecutive patients with coagulopathy (INR >1.4; n=20),
      thrombocytopenia (platelet count <75,000/cmm; n=17), ascites (n=10), or
      coagulopathy and thrombocytopenia (n=3) from April 1999 to July 2002 were
      analyzed. Biopsy was performed under local anesthesia with fluoroscopic guidance,
      using the Quick Core biopsy needle. RESULTS: Ninety-two needle passes were made
      to obtain 84 samples. Biopsy was technically unsuccessful in two patients because
      of hepatic vein ostial block; however, the procedure established the diagnosis of
      blockage of hepatic vein ostia in these patients. Biopsy specimen was adequate
      for histological examination in 45 patients. The median number of biopsies
      performed with 18- and 19-gauge needles was 14 and 8, respectively. The biopsy
      provided diagnostic information in 23 of 50 (46%) patients, and helped in staging
      or providing prognostic information in 37 (74%) patients. There were no major
      complications. Minor complications included transient hepatic vein-to-portal vein
      fistula in 2, transient hepatic vein-biliary fistula in one, local hematoma in 5,
      and post-procedure fever in 5 patients. The approximate cost of the needle and
      accessories was Rs. 2000 per patient. CONCLUSIONS: Transjugular liver biopsy was
      safe, provided adequate tissue in 90% of patients, and helped frequently in
      diagnosis and in staging or prognostication of disease.

PMID- 14658533
TI  - Pulmonary and hematological alterations in idiopathic ulcerative colitis.
AB  - BACKGROUND: Patients with idiopathic ulcerative colitis (IUC) may suffer from one
      or more extraintestinal manifestations. We decided to prospectively study the
      prevalence of extraintestinal manifestations among patients with IUC, with
      special reference to pulmonary and hematological alterations. METHODS: Fifty-one
      consecutive patients with IUC attending the gastroenterology services of our
      tertiary-care referral center were evaluated prospectively. A detailed clinical
      evaluation of the musculoskeletal system, eye and skin, X-ray examination of the
      sacroiliac joints and chest, liver function tests, coagulation profile, hemogram,
      pulmonary function tests (PFT) and diffusion capacity for carbon monoxide (DLCO)
      were done in all patients. ERCP, liver biopsy and high-resolution computerized
      tomography (HRCT) of the chest were performed whenever indicated. RESULTS: Nearly
      half (24/51; 47%) the patients had one or more extraintestinal manifestations;
      these included pulmonary function abnormalities (14 patients; 27%), sacroiliitis
      (8; 16%), arthritis (5; 10%), ocular complications (4; 8%), and pyoderma
      gangrenosum and Budd-Chiari syndrome (one patient each). Of the 14 (27%) patients
      who had abnormal pulmonary function, isolated PFT abnormalities were seen in 8
      (restrictive pattern in 7, obstructive pattern in 1), decreased DLCO in four, and
      both of the above in two. All patients with decreased DLCO (n=6) were
      asymptomatic and had normal chest X-ray and HRCT chest. Thirteen (25%) patients
      had thrombocytosis, 19 (37%) had increased fibrinogen level, and one patient had
      decreased antithrombin level. Disease activity had significant association with
      decreased DLCO (p=0.008), increased platelet count (p<0.0001), increased
      fibrinogen level (p=0.016), low antithrombin levels (p=0.046) and arthritis
      (p=0.002). CONCLUSION: Extraintestinal manifestations of IUC were seen in 47% of
      patients. Asymptomatic pulmonary interstitial involvement was seen in 12%, more
      often among patients with active disease.

PMID- 14658534
TI  - Hepatitis C virus genotypes: special reference to the Indian scene.
AB  - The heterogeneity observed between different isolates of the hepatitis C virus
      has led to stratification of these isolates into different genotypes. Clinically
      the genetic diversity of the virus has important implications as genotypes
      respond variably to antiviral therapy and can influence disease prognosis. This
      article attempts to summarize current knowledge about the different biological
      properties of HCV genotypes, and their geographical distribution, with special
      reference to the Indian scenario.

PMID- 14658535
TI  - Transendoscopic fine needle aspiration cytology in the diagnosis of
      hepatocellular carcinoma.
AB  - This report describes the use of transendoscopic fine needle aspiration cytology
      in the diagnosis of three cases of hepatocellular carcinoma who had presented
      with large nodular liver and mass impression on the left border of the stomach at
      endoscopy. Using a 21G, 1.0 cm needle catheter, transendoscopic fine needle
      aspiration was done under direct endoscopic vision. The aspirate confirmed the
      diagnosis of hepatocellular carcinoma in all of them.

PMID- 14658536
TI  - Cronkhite-Canada syndrome with adenomatous and carcinomatous transformation of
      colonic polyp.
AB  - We describe a 70-year-old woman who presented with watery diarrhea and was found
      to have gastric and colonic polyposis, cutaneous hyperpigmentation, alopecia and
      onychodystrophy (Cronkhite-Canada syndrome). Histology of a polyp from the
      stomach showed features of juvenile or retention type (hamartomatous) polyp. One
      colonic polyp revealed features of tubular adenoma, with moderate dysplasia.
      Another large pedunculated colonic polyp showed a tubulovillous adenoma with a
      focus of well-differentiated adenocarcinoma confined to the submucosa of the
      stalk. Adenomatous and carcinomatous epithelial changes can occur in Cronkhite
      Canada syndrome.

PMID- 14658537
TI  - Brucella: a rare causative agent of spontaneous bacterial peritonitis.
AB  - We report a 54-year-old woman with hepatitis B-related chronic liver disease with
      ascites who developed spontaneous bacterial peritonitis. Blood and fluid cultures
      grew Brucella; the patient was working at an animal husbandry till one year ago.
      She responded to therapy with streptomycin and tetracycline.

PMID- 14658538
TI  - Abdominal wall abscess secondary to subcapsular tubercular liver abscess.
AB  - We report a 22-year-old woman who presented with an abdominal wall lump in the
      right upper quadrant 15 days after starting antitubercular treatment for right
      pleural effusion. CT scan revealed a right liver lobe subcapsular abscess
      communicating vith subcutaneous tissue. Aspiration of pus revealed acid-fast
      bacilli. She responded to 9 months of antitubercular treatment.

PMID- 14658539
TI  - Micropneumatosis coexistent with Helicobacter pylori and its improvement.
AB  - Micropneumatosis intestinalis is the occurrence of gas-filled circular voids with
      diameter of 20-200 microns, not lined with epithelium. We report a 39-year-old
      man with superficial gastritis and Helicobacter pylori infection who also had
      gastric, duodenal and colonic micropneumatosis. Endoscopic biopsy after treatment
      for H. pylori gastritis showed no micropneumatosis in gastric, duodenal or
      colonic mucosal sections. We suggest that H. pylori may be one of the causative
      factors for micropneumatosis.

PMID- 14658540
TI  - Thrombocytopenic purpura as initial presentation of acute hepatitis A.
AB  - Extrahepatic immune manifestations are rare in hepatitis A virus infection. We
      report a 4 1/2-year-old girl who presented with thrombocytopenic purpura as
      initial manifestation of hepatitis A virus infection. She responded to steroid
      therapy.

PMID- 14658541
TI  - Association of ulcerative colitis with pulmonary sarcoidosis, subcutaneous
      lipomatosis and appendiceal adenocarcinoma.
AB  - We report a 52-year-old man with left-sided ulcerative colitis for 5 years and
      pulmonary sarcoidosis diagnosed 3 years back. He presented with subcutaneous
      lipomatosis and a right iliac fossa mass, which was diagnosed histologically as
      appendiceal adenocarcinoma. He was treated with right hemicolectomy, followed by
      chemotherapy.

PMID- 14658542
TI  - Torsion of the greater omentum with inguinal hernia.
AB  - Torsion of the greater omentum is an uncommon cause of acute abdomen, often
      diagnosed only intraoperatively. We report a 30-year-old man with torsion of the
      greater omentum in association with inguinal hernia, diagnosed on CT scan and
      managed conservatively.

PMID- 14658543
TI  - Multiple myeloma with amyloidosis presenting with recurrent gastrointestinal
      bleeding.
AB  - We report a 45-year-old woman who presented with hematemesis. Endoscopy showed
      nodular lesions and ulcers in the gastric antrum; histology of the lesions showed
      amyloidosis. The patient had received melphalan and prednisolone for multiple
      myeloma 5 years earlier.

PMID- 14658544
TI  - Stapler versus suture technique of mesh in Lichtenstein repair for inguinal
      hernia.

PMID- 14658545
TI  - Gastroesophageal reflux disease in children: need for long-term medical
      treatment.

PMID- 14658546
TI  - Liver infarction presenting with shock.

PMID- 14658547
TI  - Schwannoma of the transverse mesocolon.

PMID- 14658548
TI  - Retrograde jejuno-jejunal intussusception.

PMID- 14658549
TI  - Food's many meanings.

PMID- 14658550
TI  - Student debt.

PMID- 14658551
TI  - Palatable prevention.

PMID- 14658552
TI  - Crossing fields.

PMID- 14658553
TI  - Obesity in children.

PMID- 14658554
TI  - Culinary hygiene: some hints on preparation and selection of food. 1904
      [classical article].

PMID- 14658555
TI  - Animal pathogens and food safety.

PMID- 14658556
TI  - Diet and nutrition--what should we eat?
AB  - Patients and their physicians remain confused about which dietary advice to
      follow. Substantial evidence indicates that energy-appropriate, whole-food diets
      containing unrefined grains, an abundance of fruits and vegetables, low-fat dairy
      products, low-fat protein sources, and carefully chosen fats and oils can
      contribute significantly to chronic disease risk reduction. This article focuses
      on dietary composition with respect to energy-providing macronutrients, such as
      carbohydrate, protein, and fat; addresses dietary topics of current interest,
      such as glycemic index, whole grains, and plant sterols; and presents evidence
      based research on adequate intake levels of macronutrients for optimal nutrition
      and disease risk reduction.

PMID- 14658557
TI  - Current challenges in recognizing and treating eating disorders.
AB  - Anorexia nervosa and bulimia nervosa are serious, life-threatening illnesses that
      often require several years of treatment. Although classified as mental health
      diagnoses, they are associated with significant medical consequences and have the
      highest rate of premature death of any mental health diagnosis. They also are
      associated with the highest rate of short- and long-term physiological
      complications. Eating disorders disproportionately affect young women. With early
      intervention and aggressive treatment, affected adolescents and young adults can
      recover and be free of the disorder. This article reviews the difficulties in
      recognizing that a patient has an eating disorder and the signs and symptoms
      providers should look for. It also discusses our current understanding of the
      causes of eating disorders as well as current treatment methods, which involve a
      multidisciplinary approach.

PMID- 14658558
TI  - Food as medicine--cost-effective health care? The example of omega-3 fatty acids.
AB  - The United States accounts for more than 51% of the dollar 430.3 billion expended
      on pharmaceutical products worldwide each year. Yet, in comparison to other
      advanced industrial societies, the United States has relatively worse health
      outcomes across many measures. This disparity challenges the perceived efficacy
      and cost effectiveness of pharmaceutical agents in promoting the public health.
      Before access to prescription drugs, our society first needs access to low-cost,
      nontoxic, non-expert-dependent interventions to ensure basic health outcomes.
      Food may represent the most cost-effective means of promoting public health. This
      article introduces the topic of food as medicine by discussing briefly the
      evidence base for omega-3 fatty acid-rich foods as modulators of physiologic
      pathways. It provides background on the physiological role of omega-3 and omega-6
      fatty acids, discusses their roles in disease and disease prevention, and looks
      at changes in food production in this country that have led to a decrease in
      omega-3 consumption. It also recommends dietary interventions to remedy omega-3
      deficiency and asserts that now is the time for our state and our nation to more
      aggressively fund research into medicinal foods.

PMID- 14658559
TI  - "We have met the enemy, and ...".

PMID- 14658560
TI  - Health care costs a growing concern.

PMID- 14658561
TI  - No ice cream?

PMID- 14658562
TI  - The Wisconsin State Laboratory of Hygiene: century of service and progress.

PMID- 14658563
TI  - The current and future roles of the Wisconsin State Laboratory of Hygiene.

PMID- 14658564
TI  - Laboratory-based surveillance for influenza: role of the Wisconsin State
      Laboratory of Hygiene.
AB  - Influenza poses a significant threat to public health worldwide. In the United
      States alone, mortality attributed to annual epidemics of influenza is estimated
      at 36,000 deaths per year. Influenza viruses also cause pandemics, during which
      the rates of illness and death can be expected to be much higher. In order to
      optimize prevention and control strategies for influenza, a variety of
      surveillance activities are carried out year-round internationally, nationally,
      and at the state level. This article summarizes relevant features of influenza
      and the surveillance activities carried out at each of these levels to monitor
      influenza activity. Particular emphasis is given to the state's laboratory-based
      surveillance network, developed and coordinated by the Wisconsin State Laboratory
      of Hygiene, that features strong and productive partnerships with private sector
      clinicians and laboratories and that provides a solid foundation for surveillance
      directed at other public health threats such as Severe Acute Respiratory Syndrome
      and bioterrorism.

PMID- 14658565
TI  - Laboratory role in tuberculosis control.
AB  - The term "tuberculosis" (TB) refers to infection with the bacterium Mycobacterium
      tuberculosis that has progressed to active disease. This disease is a public
      health threat because it is caused by a microorganism that is potentially fatal
      for humans, and transmission is commonly through the inhalation of airborne
      droplets expelled by infectious persons with active disease. The World Health
      Organization (WHO) estimates that there are more than 8 million new cases of TB
      each year, 2 million deaths from the disease each year, and that one-third of the
      world population is infected with M. tuberculosis and at risk for active disease.
      In 2003, the 100-year anniversary of the founding of the Wisconsin State
      Laboratory of Hygiene (WSLH), TB is recognized as a disease that is preventable
      and now almost always treatable. An early and accurate diagnosis of TB is perhaps
      the most significant intervention step in TB control. Early diagnosis permits
      expedited treatment and limitation of spread. An effective TB laboratory program
      plays an essential role in the early and accurate diagnosis and appropriate
      treatment of TB. This article examines that role.

PMID- 14658566
TI  - Targeted laboratory screening for sexually transmitted and bloodborne infections
      in Wisconsin.
AB  - Public health laboratories play an important role in screening programs for
      asymptomatic diseases of public health importance in high-risk and underserved
      populations. The implementation of targeted screening strategies for communicable
      diseases requires thorough planning and evaluation. The Wisconsin State
      Laboratory of Hygiene (WSLH) systematically selects and evaluates laboratory
      tests used in communicable disease control programs coordinated by the Wisconsin
      Division of Public Health. To do this, the epidemiologic features of the disease
      in potential target populations are carefully assessed, with the choice of
      laboratory tests based on performance as well as practical and cost
      considerations. Laboratory testing at WSLH plays a crucial role in screening
      programs for sexually transmitted and bloodborne infections. Hallmarks of these
      programs are cross-sector collaboration, empirical selection of laboratory
      testing methods, and the use of epidemiologic data to develop and evaluate
      targeted screening strategies.

PMID- 14658567
TI  - The Wisconsin State Laboratory of Hygiene and emerging enteric pathogens.
AB  - At the turn of the 20th century, typhoid fever was common in Wisconsin, and was a
      major impetus for the establishment of the Wisconsin State Laboratory of Hygiene
      (WSLH) in 1903. By the 1940s, typhoid was virtually eliminated in the United
      States due to public health measures such as disinfection of drinking water,
      sewage treatment, pasteurization, and shellfish bed sanitation. However, new food
      and waterborne pathogens have emerged to take the place of Salmonella Typhi.
      Infections with non-typhoidal Salmonella strains in the United States have
      increased almost 10-fold since the 1950s. In the last 20 years, the emergence of
      foodborne pathogens, such as Escherichia coli O157:H7, Cyclospora cayetanensis,
      Noroviruses (Norwalk-like viruses), Cryptosporidium parvum, Campylobacter jejuni,
      Yersinia enterocolitica, and multi-drug-resistant Salmonella, has identified a
      need for accurate laboratory diagnosis of enteric disease and outbreaks.

PMID- 14658568
TI  - Screening newborns for congenital disorders.
AB  - The Newborn Screening Laboratory at the Wisconsin State Laboratory of Hygiene
      (WSLH) tests all newborn babies in the state of Wisconsin for 26 congenital
      disorders. The screening is mandated by state statute (253.13) and attempts to
      identify those babies at highest risk for any of the screened-for congenital
      disorders. The Newborn Screening Laboratory at the WSLH is part of the state's
      newborn screening program, a cooperative effort between the Wisconsin Department
      of Health and Family Services, state birthing hospital staff, several public and
      private specialty clinics, primary care providers, and parents. Screening occurs
      within the first hours (median 38 hours) of life when a few drops of blood from
      the baby's heel is collected, applied to a special paper, dried, and sent to the
      WSLH for analysis. Those babies determined to have at-risk test results get
      repeat testing to confirm the initial test results and, if warranted, the baby is
      referred to a specialty clinic for a diagnostic work-up and treatment if
      necessary. Since its inception in the early 1960s, newborn screening in Wisconsin
      has saved approximately 1300 children from serious mental or other medical
      problems.

PMID- 14658569
TI  - Recent developments in cervical cancer control.
AB  - The Wisconsin State Laboratory of Hygiene's Cytology Program has contributed to
      the success of the Pap smear in substantially decreasing the number of cervical
      cancers in the United States. In addition to providing testing services to the
      Cervical Cancer Control Program of Wisconsin, the Department of Health and Family
      Services, and Planned Parenthood of Wisconsin, the Wisconsin State Laboratory of
      Hygiene (WSLH) maintains one of the largest schools of cytotechnology in the
      United States, which helps train individuals into a profession experiencing
      severe shortages. The Cytology Program has actively evaluated the new liquid
      based testing technology to provide data to improve laboratory performance. Staff
      at the WSLH have participated in the evolution of cytopathology by serving on
      governmental committees and on professional cytopathology organizations. The WSLH
      Cytology Program is now evaluating the role of molecular technology, including
      human papilloma virus testing, to improve the diagnosis and treatment of cervical
      cancers.

PMID- 14658570
TI  - Wisconsin State Laboratory of Hygiene's role in clinical laboratory improvement.
AB  - The clinical laboratory at the beginning of the 21st century is a highly
      automated, multi-faceted entity, capable of turning out complex test results on a
      variety of samples in a relatively short period of time. These test results are
      used by physicians to diagnose illness, establish treatment strategies, and
      monitor therapies for patients. They must be of the highest quality and
      reliability to insure that the course of action taken by the health care provider
      will lead to the best possible outcome for the patient.

PMID- 14658571
TI  - The State Laboratory of Hygiene's role in terrorism preparedness and response.
AB  - In the fall of 2001, the national public health system found itself responding to
      acts of terrorism. The intentional release of Bacillus anthracis spores on the
      East Coast tested the capacity of all state public health laboratories to
      respond. The impact on the public health system extended to the Wisconsin State
      Laboratory of Hygiene (WSLH). Fortunately, participation in the National
      Laboratory Response Network helped the WSLH meet the challenge of 24 hour/7 days
      a week coverage, and subsequent federal funding increases have enabled the WSLH
      to expand its technical capabilities and provide training and outreach to other
      Wisconsin laboratories to prepare them for their roles in man-made or naturally
      occurring public health emergencies.

PMID- 14658572
TI  - Prenatal screening at the Wisconsin State Laboratory of Hygiene.

PMID- 14658573
TI  - Occupational and industrial health at the Wisconsin State Laboratory of Hygiene.
AB  - Occupational hazards have been known for centuries, but the creation of
      facilities capable of carrying out the testing necessary to assess these risks is
      a comparatively recent development. The Wisconsin State Laboratory of Hygiene
      (WSLH) created the Wisconsin Occupational Health Laboratory (WOHL) in 1937 to
      address this need. Since then, WOHL's range of analytical capacity has grown to
      include an impressive array of assays, including volatile organic compounds,
      asbestos, silica, environmental lead, bioaerosols, and elemental carbon. WOHL has
      been a leader in emerging occupational health threats, and has been the primary
      testing facility for the United State's Occupational Safety and Health
      Administration's (OSHA) consultation program since 1977. Through it all, WOHL has
      remained a fee-for-service branch of the WSLH and has not used Wisconsin taxpayer
      funds to support its day-to-day operations.

PMID- 14658574
TI  - Protecting the waters of Wisconsin from microbiological threats.
AB  - Wisconsin is blessed with an abundance of high quality water that has played a
      significant role in the economic and social development of the state. The quality
      of life for Wisconsinites is often at least partially defined by pristine inland
      lakes, a portion of the Great Lakes shoreline, or great-tasting well water. While
      no one likes to associate water with disease, especially waters like those we
      enjoy in Wisconsin, the historical reality is that there is a strong connection.
      Until the 1920s, intestinal diseases such as typhoid fever and cholera often
      spread through water and were a leading cause of death in the United States.
      While easy access to modern medical care combined with improved water treatment
      technologies have greatly decreased waterborne disease, the microbiology of
      Wisconsin's waters still deserves continued vigilance and attention. The World
      Health Organization currently estimates that, on a global basis, 4 billion annual
      cases of waterborne diarrhea result in more than 2 million deaths per year--the
      equivalent of 20 jumbo jet crashes per day. Most of these deaths are in children
      under 5 years of age. The daily global death toll from waterborne disease is at
      least 1000 times greater than from the Severe Acute Respiratory Syndrome epidemic
      that recently made headline news. Waterborne disease is not just a problem in
      underdeveloped countries. Scientists who study disease transmission believe that
      10%-30% of the vomiting and diarrhea illness in North America, including
      Wisconsin, may be acquired from water.

PMID- 14658575
TI  - Forensic Toxicology Program: alcohol and drug testing in Wisconsin drivers.
AB  - The Forensic Toxicology Program of the Wisconsin State Laboratory of Hygiene
      (WSLH) provides analytical and support services to assist in the identification
      of alcohol- and/or drug-impaired drivers and to assist in determining cause of
      death. These services are provided to law enforcement agencies, the Wisconsin
      Department of Natural Resources, the Wisconsin Department of Transportation, and
      county medical examiners and coroners. Program staff is active in alcohol and
      drug training, policy-making, and research on a national and international level.

PMID- 14658576
TI  - Outdoor air pollution activities at the Wisconsin State Laboratory of Hygiene.
AB  - Outdoor air quality testing at the Wisconsin State Laboratory of Hygiene (WSLH)
      began in the 1970s with the advent of the federal Clean Air Act. Since then, air
      quality has emerged as a major environmental issue equal to or more important,
      from a public health standpoint, than water pollution. Epidemiological studies
      have shown that health issues are not limited to highly urbanized areas. In
      Wisconsin, local climatic conditions caused by the Great Lakes can result in
      unhealthy conditions even in relatively pristine areas. Air pollution affects
      thousands of Wisconsin residents each year, and it can be severe enough to
      require a physician's care. Although certain air testing (e.g., ozone) is done
      regionally by in situ monitors, the WSLH analyzes a variety of air pollutants
      including ozone precursor hydrocarbons, air particulates, and toxic metals.
      Exposure to aerosols containing metals may not follow typical patterns of air
      pollution based on routinely monitored particle mass.

PMID- 14658577
TI  - A fruitful and gratifying collaboration.

PMID- 14658578
TI  - CMS offers CME program for quality improvement.

PMID- 14658579
TI  - Estate planning for the second time around.

PMID- 14658580
TI  - Adjuvant radiotherapy in Stage I endometrial cancer. Where do we stand?
AB  - This paper reviews the anatomical spread and failure patterns of surgical Stage I
      endometrial cancer. The controversial aspects of the optimal adjuvant treatment
      are presented. An attempt is made to identify the most effective management
      approach based on the pertinent literature data.

PMID- 14658581
TI  - BRCA susceptibility genes--a review of current conservative management of BRCA
      mutation carriers.
AB  - Three options for the management of a patient carrying a deleterious mutation in
      the BRCA gene exist: close surveillance, chemoprevention and prophylactic
      surgical procedures. We aimed at reviewing the current knowledge on the
      conservative management of patients who are found to be carriers of the BRCA
      susceptibility genes. Recent literature in the English language was reviewed for
      publications containing the conservative management of BRCA mutation-carriers.
      Close surveillance for the breasts includes breast self-examination, clinical
      examination by a specialist and breast imaging techniques--mammography and
      magnetic resonance imaging. Ovarian surveillance includes pelvic examination,
      transvaginal ultrasonography and blood CA-125 measurements. Age at beginning of
      examinations and their frequency are discussed. Chemoprevention includes
      tamoxifen and oral contraceptives for breast and ovarian cancer prevention,
      respectively.

PMID- 14658582
TI  - The role of neoadjuvant chemotherapy followed by radical surgery in the treatment
      of locally advanced cervical cancer.
AB  - In 1984 the first pilot study on neoadjuvant chemotherapy in cervical cancer was
      reported. Since then, many investigators have studied the possible role that this
      therapeutic strategy could achieve in patients. Different chemotherapic
      combinations are constantly being attempted in order to obtain the maximum tumour
      response. At the same time few randomised studies have demonstrated the
      superiority of this treatment when adopted before radical surgery, in terms of
      overall survival compared to radiotherapy alone. Recently a detailed meta
      analysis has been performed and the results confirmed what previously was
      achieved by the randomised trials. Since the beginning of all the phase III
      trials, the standard treatment of locally advanced disease has been modified from
      radiotherapy alone to concomitant radio-chemotherapy. For this reason the EORTC
      group has launched a trial with the objective of comparing neoadjuvant
      chemotherapy followed by radical surgery versus concomitant chemo-radiotherapy.

PMID- 14658583
TI  - Options for laparoscopic surgery in cervical carcinomas.
AB  - The laparoscopy in vaginal surgical technique in the therapy of cervical cancer
      causes some scepticism. However the results, particularly for lymphadenectomy,
      are very interesting. Moreover laparoscopic staging of cervical cancer can also
      be recommended when preoperative chemotherapy is planned. Using the laparoscopic
      staging method the treatment of the patient may be more individualized.

PMID- 14658584
TI  - Palliative cytostatic treatment of cervical carcinoma.
AB  - PURPOSE OF THE ARTICLE: In patients recurring after primary therapy for cervical
      cancer, treatment remains palliative. In the present article we focus on
      treatment results with single cytostatic drugs or combinations in randomized
      trials in squamous cell cervical cancer. RESULTS: In one randomized trial,
      monotherapy with platinum analogues lead to overall remission rates between 11%
      and 15% only. The median overall survival ranged between 5.6 and 6.5 months.
      Various combinations lead to overall remission rates between 21% and 31% and the
      median overall survival ranged between 7.3 and 14.3 months. The most active
      combinations were cisplatin/bleomycin/mitomycin C/vindesine,
      cisplatin/paclitaxel, and cisplatin/irinotecan. There are several smaller studies
      with cystostatic therapy in cervical adenocarcinoma. However, using 5
      fluoruracil, ifosfamide, paclitaxel, or cisplatinum, only response rates between
      15 and 30% can be achieved. Predictors of a favorable chemotherapy response
      include a higher performance status, higher age, extrapelvic recurrence sites
      (especially lung metastases), a recurrence-free interval > 1 year, and no
      previous radiotherapy and chemotherapy. CONCLUSION: In conclusion, palliative
      cytostatic therapy with single agents has moderate activity. Combinations are
      more active but also more toxic. In general, chemotherapy needs to be used
      earlier in the course of disease when tissue vascularization is preserved.

PMID- 14658585
TI  - Current state-of-the-art of concomitant chemoradiation in cervical carcinomas.
AB  - Despite screening programs, cervical carcinoma remains a major health problem
      throughout the world. Until recently pelvic radiation has been the standard
      therapy for advanced disease with overall five-year survival rates of 50%.
      Recently, five randomized trials demonstrated a significant survival advantage
      for the concomitant administration of radiotherapy and cisplatin-based
      chemotherapy. Although the trials vary somewhat in terms of stage of disease,
      dose of radiation, and schedule of radiation and cisplatin, they all demonstrated
      a significant survival benefit for the combined approach. Congruent to these
      findings are results from a meta-analysis based on the data from 19 trials with
      4,580 randomized patients. The absolute increase in progression-free and overall
      survival was 16% and 12%, respectively. Contrary to these findings is the result
      of the National Cancer Institute of Canada (NCCI) trial. Despite that result
      cisplatin-based concomitant chemoradiotherapy has become the standard treatment
      of locally advanced cervical cancer.

PMID- 14658587
TI  - Lower urinary tract function after postoperative radiotherapy in the treatment of
      cervical cancer.
AB  - OBJECTIVE: The aim of this study was the urodynamic assessment of lower urinary
      tract disturbance intensity (especially urinary incontinence) among irradiated
      women after the surgical treatment of cervical cancer. STUDY DESIGN: The analysis
      included 34 patients after radical hysterectomy and following radiotherapy for
      cervical cancer in clinical Stage Ib. Only patients without any previous
      urogynecological disorders were included. Urodynamic diagnostics was performed
      two weeks after oncological treatment termination. RESULTS: Urodynamic parameter
      changes were clearly present at all stages of functional diagnostics. The most
      remarkable changes included decreased bladder capacity (mean 196 ml) and residual
      urine volume (mean 19 ml). The mean value of maximal urine flow rate obtained
      from uroflowmetry was 26 ml/s, but for 20 women it was lower than 20 ml/s.
      Voiding time and flow time were abnormally delayed with the significant
      difference of five seconds. Bladder sensation points were increased and maximum
      cystometric capacity was decreased to 270 ml during filling cystometry. Bladder
      compliance was 28 ml/cm H2O on average; for the majority of patients it was below
      20. Detrusor pressure was increased in 23 cases above 20 cm H2O and mean
      isometric pressure was 34 cm H2O. Urethral pressures were low, especially while
      taking effort. Urinary incontinence was diagnosed in 30% of the cases.
      CONCLUSIONS: The obtained results allow us to conclude that voiding disorders
      after combined radiotherapy and surgery are often and mainly apply to the
      detrusor muscle with the domination of functional disturbances. It seems that
      early quantitative and qualitative changes depend on combined therapy with a
      standard dose pattern. The presence of functional disorders after oncological
      treatment should be considered in the planning of prevention and further
      treatment. Urinary incontinence restricts patients' activity, affects the quality
      of their lives and is the cause of patient discomfort. Many patients suffering
      from lower urinary tract pathologies pose a therapeutic problem caused by lack of
      information.

PMID- 14658586
TI  - Filgrastim support during combination chemotherapy using cisplatin, doxorubicin,
      and cyclophosphamide to treat advanced or recurrent endometrial cancer: a
      clinical study and literature review.
AB  - In a private practice setting, 16 patients with advanced or recurrent endometrial
      carcinoma received cisplatinum 50 mg/m2, doxorubicin 50 mg/m2, and
      cyclophosphamide 750 mg/m2 every three weeks. Growth factor support using
      filgrastim was initiated on the first cycle of therapy and each subsequent cycle.
      Sixteen patients were entered into the study with 13 being evaluable. No patient
      had previously received chemotherapy. The overall response rate was 54% with two
      complete responses (15%) and five partial responses (38%). Stable disease was
      seen in 46% of patients. Progression-free survival was observed to be a median of
      8.5 months for a complete response, a median of 8.5 months for a partial response
      and a median of 7 months for stable disease. Fifteen percent of the patients and
      3% of all chemotherapy cycles had febrile neutropenic events. There were no
      deaths due to myelotoxicity. Only one patient required a dose reduction due to
      neutropenia. Four of the 13 patients required dose reductions due to previous
      nadir thrombocytopenia. Grade 4 granulocytopenia occurred in 28% of treatment
      cycles and grade 3 granulocytopenia occurred in 12% of treatment cycles. The use
      of filgrastim (G-CSF) allowed patients to stay on therapy for an average of seven
      treatments. Neutropenia was not the dose-limiting toxicity from this dose-intense
      regimen.

PMID- 14658588
TI  - Improved early detection of cervical intraepithelial lesions by combination of
      conventional Pap smear and speculoscopy.
AB  - PURPOSE: To evaluate the efficacy of the addition of speculoscopy to a Pap smear
      in cervical cancer screening. METHODS: All women were screened using the Pap
      smear plus speculoscopy (PapSure) and colposcopy in the multicenter trial. The
      final diagnosis of each patient was based on a histological evaluation of the
      colposcopic target biopsy. Results were analyzed using a proportional compare
      test, sensitivity, specificity and predictive value with significant value
      determined at less than 0.05. RESULTS: Of 1,717 eligible cases, 26 cases had
      LGSIL and 16 cases had HGSIL. Of the Pap smears, five cases had LSIL and 14 cases
      had HGSIL. Of the combination of the PapSure, 23 cases had LGSIL and 16 cases had
      HGSIL. The sensitivity of the Pap smear to that of PapSure was calculated at
      45.2% and 92.9%, respectively (p < 0.001). The estimated cost to detect a
      cervical lesion using PapSure is less than that of the Pap smear. CONCLUSION: The
      addition of speculoscopy along with a Pap smear screening results in early
      detection of cervical lesions in comparison to the Pap smear alone. This
      screening combination is also more cost-effective and requires fewer visits to
      the clinic in comparison to a Pap smear screening alone.

PMID- 14658589
TI  - Glycoprotein CD44 expression in normal, hyperplasic and neoplastic endometrium.
      An immunohistochemical study including correlations with p53, steroid receptor
      status and proliferative indices (PCNA, MIB1).
AB  - PURPOSE OF INVESTIGATION: We have studied by immunohistochemistry the presence
      and localization of CD44, estrogen and progesterone receptors, p53 and
      proliferative associated indices (MIB1, PCNA) in archival endometrial tissue, in
      order to determine their diagnostic and prognostic value as well as the possible
      correlations between them. METHODS: We examined 186 samples of endometrial tissue
      (100 endometrial carcinomas of endometrioid type, 40 cases of hyperplasia and 46
      of normal endometrium). Patient records were examined for FIGO stage, grade, and
      depth of myometrial invasion, histology, and lympho-vascular space invasion.
      RESULTS: Strong membranous immunostaining (> 10% of neoplastic cells) was
      observed in 45% of the carcinomas. A statistically significant correlation was
      found in the expression of protein in stromal cells, when compared with
      epithelial cells (p < 0.0001). Immunohistochemical expression of CD44 was
      significantly lower in cancer cases than in normal endometrium, mainly in the
      secretory phase (p < 0.0001). CD44 positive cases by immunohistochemistry failed
      to show any statistical correlation with tumor grade or with vessel invasion. The
      expression of the protein was lower in FIGO Stage II compared with Stage I (p =
      0.03). A positive relation of CD44 expression with progesterone receptor status
      (p = 0.02) was detected. CD44 expression was also positively associated with the
      proliferation associated with the proliferative index MIB1 (p = 0.001).
      CONCLUSION: CD44 is closely related to the secretory phase of the normal
      menstrual cycle and its expression is decreased in hyperplasia (simple or complex
      with or without atypia) and in cancer cases. These observations suggest that
      decreased CD44 expression might be functionally involved in the multiple
      mechanisms of the development and progression of endometrial lesions.

PMID- 14658590
TI  - Leiomyosarcoma of the broad ligament arising in a pre-existing pure neurilemmoma
      like leiomyoma.
AB  - A 35-year-old woman presented with an adnexal mass which came out as a
      leiomyosarcoma of the broad ligament arising in a pre-existing pure neurilemmoma
      like leiomyoma. This is the first reported case of leiomyosarcoma arising in a
      pure neurilemmoma-like leiomyoma, the third reported case at an unusually young
      age showing evidence of a pre-existing leiomyoma and the 12th reported case of
      leimyosarcoma of the broad ligament. Is the likelihood of malignant
      transformation, especially in large leiomyomas of the broad ligament, a rare
      event?

PMID- 14658591
TI  - Hormonal replacement therapy and evaluation of intrauterine pathology in
      postmenopausal women: a ten-year study.
AB  - BACKGROUND: To evaluate the role of hormonal replacement therapy (HRT) in
      determining: a) abnormal uterine bleeding (AUB); b) increased endometrial
      thickness at transvaginal sonography (TVS); c) the correct indication for
      outpatient hysteroscopy (HS) and biopsy in diagnosing intrauterine pathology.
      METHODS: Between April 1991 and April 2001 a group of 3,400 postmenopausal women
      was referred to the Department of Obstetrics and Gynecology of Rome University
      "La Sapienza"; 16.7% of them had received HRT. 587 out of the 3,400 women were
      recruited for a comparative study, including four groups. To assess statistical
      significance of HRT in determining AUB, and/or endometrial thickness related to
      malignant disease the chi-square test was used; p < 0.05 was considered
      significant. Histology was considered the true result (control). RESULTS: An
      increase in the endometrial thickness occurred significantly more often in women
      on HRT (p < 0.03); as well as the percentage of AUB (p < 0.0001). No difference
      in the incidence of endometrial adenocarcinoma was reported between the HRT and
      the non HRT groups. CONCLUSIONS: In postmenopausal women using HRT we can confirm
      that a higher incidence of signs (AUB, endometrial thickness > or = 5 mm) does
      not coincide with a higher incidence of malignant pathology. The data obtained
      from the recruited patients was arranged and evaluated by the most suitable
      methods for screening endometrial adenocarcinoma. According to our experience, we
      believe a cut-off point of 8 mm to be significant (p < 0.001) to perform an
      hysteroscopy and biopsy except for asymptomatic patients on HRT.

PMID- 14658592
TI  - The clinical outcome of patients with stage Ia1 and Ia2 squamous cell carcinoma
      of the uterine cervix: a Cooperation Task Force (CTF) study.
AB  - PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study
      was to assess the clinical outcome of patients with microinvasive squamous cell
      carcinoma of the uterine cervix. METHODS: The hospital records of 166 patients
      with microinvasive squamous cell carcinoma of the uterine cervix were reviewed.
      All cases were retrospectively staged according the 1994 International Federation
      of Gynecology and Obstetrics (FIGO) nomenclature. One hundred and forty-three
      cases were in Stage Ia1 and 23 in Stage Ia2 disease. Surgery consisted of
      conization alone in 30 (18.1%) patients, total hysterectomy in 82 (49.4%), and
      radical hysterectomy in 54 (32.5%). All patients in whom conization was the
      definite treatment had Stage Ia1 disease and had cone margins negative for
      intraepithelial or invasive lesions. RESULTS: None of the 67 patients submitted
      to pelvic lymphadenectomy had histologically proven metastatic lymph nodes. Of
      the 166 patients, eight (4.8%) had an intraepithelial recurrence and four (2.4%)
      had an invasive recurrence. With regard to FIGO substage, disease recurred in
      nine (6.3%) out of 143 patients with Stage Ia1 and three (13.0%) out of 23 with
      Stage Ia2 cervical cancer. With regard to type of surgery, disease recurred in
      three (10.0%) out of the patients treated with conization alone, four (4.9%) out
      those who underwent total hysterectomy, and five (9.3%) out of those who
      underwent radical hysterectomy. It is worth noting that none of the 30 patients
      treated with conization alone had recurrent invasive cancer after a median follow
      up of 45 months. However three (10%) of these patients developed a cervical
      intraepithelial neoplasia (CIN) III after 16, 33, and 94 months, respectively,
      from conization. CONCLUSIONS: Conization can represent the definite treatment for
      patients with Stage Ia1 squamous cell cervical cancer, if cone margins and apex
      are disease-free. For patients with Stage Ia2 cervical cancer extrafascial
      hysterectomy with pelvic lymphadenectomy might be an adequate standard therapy,
      although the need for lymph node dissection is questionable.

PMID- 14658593
TI  - Prediction of cervical infiltration in Stage II endometrial cancer by different
      preoperative evaluation techniques (D&C, US, CT, MRI).
AB  - OBJECTIVE: Our clinical practice for FIGO Stage II endometrial cancer consists of
      Wertheim's radical hysterectomy as first choice of treatment. The evaluation of
      patients is based on D&C. The accuracy of this preoperative staging method is
      examined here. METHODS: Twenty-nine patients with endometrial cancer with
      suspected cervical involvement (FIGO Stage II) based on endocervical curettage
      underwent Wertheim's radical hysterectomy between January 1, 1989 and December
      31, 2001 at the Gynaecological Department of the National Institute of Cancer,
      Budapest, Hungary. In all cases surgico-pathological staging was performed to
      examine the accuracy of preoperative D&C and to find out whether radical surgery
      was necessary in all patients and how the preoperative evaluation of patients
      should be improved. RESULTS: Out of 29 patients who underwent Wertheim's
      hysterectomy the pathological examination found primary cervical cancer in two
      patients. These two patients were eliminated from further evaluation. Out of the
      remaining 27 patients only eight (29.6%) had cervical involvement of endometrial
      cancer documented by a pathologic review on the hysterectomy specimen.
      Extrauterine disease was documented in one of the patients with cervical
      infiltration (1/8) and in one in the cervix-negative group (1/19). Ovarian spread
      was found in the first case and ovarian infiltration with penetration of the
      tumour into the parametric tissue in the second case. According to the FIGO
      classification 18 (66.6%) patients had less extensive disease and two (7.4%) had
      more extensive disease. Only 26% of the patients (7/27) had surgical findings
      consistent with the Stage II disease. CONCLUSION: We can conclude that
      "overtreatment" seems to have occurred in 19 patients, whose cervical
      infiltration by endometrial cancer could not be proved by pathological staging.
      It can also be assessed that understaging took place in two cases, which can be
      explained by two reasons; we did not make use of preoperative imaging techniques
      since US was applied in six patients, CT in 16 and the most accurate, MRI, on
      three patients only. The other possible reason, which can point out the bad
      efficacy of the imaging techniques as well, could be that a major part of the
      patients received preoperative AL treatment, which could also have influenced the
      cervical progression. This is possible, but has not been proved. The difference
      in the number of cervical infiltrations in the group of patients who received
      preoperative radiotherapy and in the group where they did not, is not significant
      (p = 0.9742), and infiltration of the endometrium was present in all cases. In
      the future, proper selection of imaging modalities can improve the staging of
      gynaecological disorders and preclude unnecessary procedures. In endometrial
      cancer cases US, especially with the use of TVUS, is often considered to be the
      primary imaging approach. However, in patients where ultrasound is suboptimal,
      where there is a large tumour present or the result of imaging studies will
      directly influence the choice of therapy and guide therapy planning then the
      higher accuracy of MRI warrants its use. CT is of use in the later stages of
      disease; differentiation between Stage I and II is difficult and CT is limited in
      the assessment of myometrial invasion.

PMID- 14658594
TI  - Malignant vulvar melanoma: colposcopic evaluation and review of the literature. A
      case report.
AB  - Because of the rarity of this kind of vulvar neoplasia, the diagnostic
      difficulties (clinical and histopathological) conditioning the therapeutic
      approach and the missing iconographical material, we report a case of vulvar
      melanoma seen at the Department of Obstetrics and Gynecology of the University of
      L'Aquila in April 2001, together with a review of the literature. Owing to
      radical vulvectomy and bilateral inguinal lymphadenectomy with the Byron three
      incision approach the histological report was: epithelioid cell apigmented
      melanoma radially spreading (MMSS), a tumor-free margin of at least 1.7 cm with
      sufficient lympholitic infiltration.

PMID- 14658595
TI  - Assessment of breast lesions using Doppler with contrast agents.
AB  - OBJECTIVE: To evaluate the use of contrast agents on ultrasound examination of
      breast lesions and to analyse the capacity of this technique to achieve a
      differential diagnosis of benign and malignant lesions, using as a pattern a
      histological study of the lesions. MATERIALS AND METHODS: Seventy-two women with
      suspected malignant breast lesions participated in this randomised prospective
      study, undergoing a colour Doppler ultrasound (US). The results of the study were
      measured before and after the use of US contrast agents and were compared with
      the ones obtained from the histological study of the pieces. RESULTS: Malignant
      breast tumours showed, when using US Doppler with contrast agent, a
      hypervascularity pattern in 78.1% of the cases. The predominant pattern in benign
      tumours was avascular (11 cases, 64.7%). The intensity of the signal in the first
      minute was intense in 43.7% or moderate in 40.6% of the cases with malignant
      tumours versus the benign tumours where no signal was registered in 64.7% of the
      cases. A marked increase in the sensitivity and the predictive negative value of
      the ultrasound signal was noted with the use of potentiating substances.
      CONCLUSIONS: The use of contrast agents in colour Doppler US studies improve the
      differential diagnosis of benign and malignant breast lesions.

PMID- 14658596
TI  - Image analysis (DNA ploidy) and expression of c-erb B-2 and p53 in imprint smears
      of breast cancer.
AB  - PURPOSE OF INVESTIGATION: To co-evaluate DNA analysis and the expression of c-erb
      B-2 and p53 oncoproteins with the histologic type and the other known prognostic
      factors of breast cancer. METHODS: Sixty-five imprint smears from breast surgical
      specimens were examined by immunocytochemical staining for c-erb B-2 and p53 and
      routine pap staining. The immunostaining was considered positive for c-erb B-2 if
      the cancer cells showed specific membrane staining and for p53 specific nuclear
      staining. In 30 breast carcinoma imprints, DNA ploidy was evaluated by an image
      analysis technique using a SAMBA 2005 analyser. RESULTS: From the total number of
      53 breast carcinomas which were evaluated in our study 25 (47.1%) showed c-erb B
      2 immunopositivity, while 16 (30.18%) exhibited p53 positive nuclear
      immunoreactivity. Ten out of 13 (76.92%) aneuploid breast carcinomas were
      positive for c-erb B-2 while five out of 13 (38.46%) showed immunopositivity for
      p53. CONCLUSION: From our findings it seems that detection of c-erb B-2 and p53
      expression in samples of breast carcinomas could be an important prognostic
      factor and may identify patients with more aggressive disease.

PMID- 14658597
TI  - The triage of squamous cell abnormalities of cervical cytology by human papilloma
      virus screening.
AB  - OBJECTIVE: The aim of the study was to determine the presence of human papilloma
      virus (HPV) infection in cervical swabs by the use of the Digene Hybrid Capture
      assay in a cohort of patients with squamous cell abnormalities found in cervical
      cytologic screening. MATERIALS AND METHODS: Thirty-four (0.3%) of 1,100 patients
      who came for their routine cervical cytologic screening and diagnosed as having
      squamous cell abnormalities were enrolled in the study. Colposcopy-directed
      biopsy was obtained from all study patients. HPV DNA was sought in cervical swab
      specimens placed in Digene transport medium by the use of the Digene Hybrid
      Capture assay. The findings of cervical cytology, colposcopy-directed biopsy and
      HPV screening were compared. RESULTS: In a total of 34 women who were diagnosed
      as having squamous cell abnormalities in their routine cervical cytologic
      screening, 15 women had atypical squamous cell lesions of undetermined
      significancy (ASCUS), 16 women had low-grade cervical intraepithelial lesions
      (LGSIL), and three women had high-grade cervical intraepithelial lesions (HGSIL).
      Five (15%) of these women tested positive for HPV screening in cervical swabs
      where four women had infection with high-risk and one woman had infection with
      low-risk subtypes. None of the patients with koilocytotic changes of the squamous
      cells in the class of LGSIL histopathologically tested positive for HPV
      screening. In addition, one patient diagnosed as having invasive cervical
      carcinoma histopathologically tested negative for HPV screening. Atypical
      vascularization was seen colposcopically in this 37-year-old woman who had ASCUS
      cytologically. CONCLUSION: HPV screening seems to have value in the triage of
      patients with ASCUS with no clear advantage to colposcopy-directed biopsy. The
      routine performance of HPV screening for the triage of patients with squamous
      cell abnormalities has no advantage over colposcopy-directed biopsy.

PMID- 14658598
TI  - Idiopathic thrombocytopenic purpura and ovarian cancer.
AB  - The association of ovarian carcinoma with idiopathic thrombocytopenic purpura
      (ITP) is rare. There have been different case reports indicating an association
      between solid tumors and ITP. We report a case of a 47-year-old woman diagnosed
      with ovarian cancer who presented with abdominal distention and thrombocytopenia.
      Her clinical course and the mechanisms of thrombocytopenia are discussed.

PMID- 14658599
TI  - Factors affecting outcome after incomplete excision of cervical intraepithelial
      neoplasia.
AB  - PURPOSE: Conservative treatment for cervical intraepithelial neoplasia (CIN) by
      ablative or excisional techniques is widely used. However, women with incomplete
      excision have a variable risk of CIN recurrence. The aim of this study was to
      identify possible risk factors for recurrence of CIN after large loop excision of
      the transformation zone (LLETZ) with involved margins of excision. METHODS: All
      cases of women treated with LLETZ for CIN between 1989-2000, in whom histological
      evaluation of the excised specimen revealed extension of CIN to the excision
      margins, were retrospectively studied. A woman was considered to have recurrence
      when she had histologically confirmed CIN following a second LLETZ or
      hysterectomy during the follow-up period. The characteristics that were examined
      as possible risk factors were age, parity, smoking habit, grade of initial lesion
      and extension to the endo- or ectocervical margin. RESULTS: Treatment failure was
      diagnosed in 18 out of 65 (27.7%) women with involved margins. The only
      characteristic that reached statistical significance was age. The mean age of
      women with recurrence was 35.8 years, whereas the mean age of women without
      recurrence was 32.8 years (p = 0.044). Also, a trend was evident in women with
      high-grade initial lesions (CIN II-III) (p = 0.168) and involvement of the
      endocervical margins (p = 0.149). No differences were observed between the two
      groups regarding parity and smoking habit. CONCLUSIONS: Increased age is a risk
      factor for recurrence in women with incomplete excision of CIN after LLETZ.
      Larger studies are required for definite conclusions.

PMID- 14658600
TI  - Immunohistochemical expression of glucose transporter Glut1 and cyclin D1 in
      breast carcinomas with negative lymph nodes.
AB  - All malignant cells appear to have increased needs for glucose in vitro as well
      as in vivo. The enhanced glucose uptake is mediated through transporters (Gluts),
      whose action and expression are regulated by oncogenes and growth factors. Cyclin
      D1 is a nuclear protein that plays an important role in regulating the cell cycle
      by promoting entry of cells from the G1 to S phase. Increased expression of Glut1
      glucose transporter and cyclin D1 have been reported in several neoplasms. In the
      present study we examined the expression of Glut1 and cyclin D1 in breast
      carcinomas with negative lymph nodes. We studied 78 infiltrating ductal
      carcinomas (25 grade 1, 36 grade 2, and 17 grade 3) with negative lymph nodes.
      Glut1 was expressed in 28% of grade 1, 63.8% of grade 2 and 58.7% of grade 3
      carcinomas. Nuclear expression of cyclin D1 was detected in 32% of grade 1, 44.4%
      of grade 2, and 41.2% of grade 3 carcinomas. From our study it appears that in
      breast carcinomas with negative lymph nodes Glut1 expression is better correlated
      to the grade of the neoplasm than cyclin D1.

PMID- 14658601
TI  - Proliferative breast disease: epidemiologic aspects, and cytologic diagnosis.
AB  - PURPOSE: The aim of the present study is to describe the prevalence of
      proliferative breast lesions in cases of benign and malignant tumors of the
      breast as well as to assess the contribution of rapid intraoperative imprint
      cytology in the diagnosis of proliferative breast disease. METHODS: Frozen
      section and intraoperative imprint cytology were performed on breast tissue
      biopsies from 486 breast cancer patients who underwent primary surgical
      treatment. Imprints were stained either by the Papanicolaou (Pap) or the May
      Grunwald-Giemsa (MGG) or the Hematoxylin eosin (HE) technique. Cytologic
      diagnoses were compared to the histopathologic ones from paraffin sections.
      RESULTS: Sclerosing adenosis was the most common finding in benign breast
      biopsies while in breast cancer the prevalence of the lesion was reduced by half.
      On the other hand, atypical hyperplasias in malignant biopsies were almost twice
      as many as in benign ones. Imprint cytology presented high sensitivity and
      specificity (99% and 96% respectively) in distinguishing benign proliferative
      from malignant lesions as a whole, but regarding atypical hyperplasias the
      specificity was significantly reduced (76% vs 96%). CONCLUSION: Clarification of
      cytologic diagnostic criteria and expertise in cytologic interpretation could
      show off intraoperative imprint cytology as a useful and inexpensive diagnostic
      tool providing the surgeon with prompt and accurate information regarding the
      nature of breast lesions.

PMID- 14658602
TI  - Computed tomography findings of primary serous papillary carcinoma of the
      peritoneum in women.
AB  - With the aim to describe preoperative computed tomography (CT) findings, the
      clinical, histopathological, and CT findings of the 12 consecutive patients with
      a confirmed diagnosis of primary peritoneal serous papillary carcinoma (PPSPC)
      were retrospectively evaluated. Of the 12 patients with a mean age of 57.5 +/-
      10.3 years, ten (83.3%) were postmenopausal. Serum Ca-125 levels were elevated in
      all patients. Ten (83.3%) had Stage III and two (16.7%) patients had Stage IV
      disease and none of the excised ovaries had deep parenchymal involvement. The
      most common CT findings were the omental (n = 11), mesenterial (n = 11) and
      parietal peritoneal involvements (n = 10), and variable amount of ascites (n =
      10). Pelvic peritoneal involvement in four (33.3%) patients was so extensive that
      it resembled a mass in the Douglas pouch. Thickening of the wall of
      gastrointestinal viscera (n = 9), lymphadenopathy (n = 5) and pleural effusion (n
      = 5) were the other CT findings and calcification was seen in only three (25.0%)
      patients. Although, none of them was characteristic, CT features of diffuse
      peritoneal, omental and mesenterial involvement especially in middle-aged or
      elderly postmenopausal women with normal-size ovaries in the absence of an
      identifiable primary site in conjunction with elevated level of serum CA-125
      should suggest the possibility of PPSPC.

PMID- 14658603
TI  - Management of advanced-stage primary carcinoma of the fallopian tube: case report
      and literature review.
AB  - Primary carcinoma of the fallopian tube is a very unusual gynecologic malignancy
      that accounts for less than 1% of all malignancies of the female genitalia. A 55
      year-old, gravida 7, para 3 woman presented with no gynecologic complaints other
      than backache. TVS demonstrated a 35 x 25 mm heterogeneous mass that was not
      clearly separated from the left ovary, and another 31 x 14 mm cystic septated
      lesion in the left ovary region. Pelvic MRI demonstrated a 35 x 35 x 20 mm left
      adnexal mass that enhanced with contrast and a neighboring tubular-cystic mass.
      Upper and lower gastrointestinal endoscopy revealed no malignancy. Serum CA 125
      level was merkedly elevated at 369 U/ml (normal < 35 U/ml). Laparotomy revealed
      left hydrosalpinx and a papillary-fimbrial mass. Pelvic lymph node metastases
      were observed. Frozen-section analysis identified the mass as a serous
      adenocarcinoma. Total abdominal hysterectomy, bilateral salpingo-oophorectomy,
      appendectomy, omentectomy, pelvic and para-aortic lymph node dissection, and
      peritoneal washing were performed. The definitive histopathological diagnosis was
      primary serous adenocarcinoma of the fallopian tube with six of 25 lymph node
      biopsies showing metastasis. Six cycles of paclitaxel (175 mg/m2) plus cisplatin
      (75 mg/m2) combinatin chemotherapy were administered with 3-week intervals
      between cycles. Second-look laparotomy was performed; there was no evidence of
      disease. At the time of writing 12 months after the second-look laparotomy, she
      was still disease-free.

PMID- 14658604
TI  - Vertebral tuberculosis presenting with elevated CA-125 and weight loss mimicking
      ovarian malignancy; case report.
AB  - Ovarian cancer is the leading cause of death among gynecologic cancers and
      currently the measurement of serum CA-125 is the most acceptable screening test.
      Here we are reporting the first case of a patient with elevated CA-125 as a
      consequence of tuberculosis vertebral osteomyelitis. Tuberculosis is a benign
      condition, which must be considered in the premenopausal female with elevated CA
      125.

PMID- 14658605
TI  - Cerebral metastasis from ovarian cancer treated with a multidisciplinary
      approach. Case report and review of literature.
AB  - Brain metastases from ovarian cancer are rare. A review of five autopsy studies
      reported brain metastases in 4% of 712 patients who died with a diagnosis of
      ovarian cancer. The prognosis is very poor and a consensus on the standard
      treatment is not available. We report the case of a patient who developed a
      solitary brain metastasis as single evidence of relapse, 26 months after the
      first diagnosis of ovarian cancer. A temporo-parietal craniotomy with excision of
      the mass and whole brain radiotherapy were performed. The patient is free of
      disease five months after radiotherapy completion. Also in patients suffering
      from neoplasms that rarely metastasize to CNS, a careful clinical examination may
      help to diagnose uncommon sites of disease relapse.

PMID- 14658606
TI  - Large endometrial polyp with sarcomatous stromal components following long-term
      tamoxifen treatment for breast cancer: a case report and review of the
      literature.
AB  - Tamoxifen is commonly used in the management of patients with breast cancer
      because of its anti-oestrogenic effects to the breasts. However, tamoxifen acts
      as an oestrogen agonist on the endometrium increasing the incidence of
      endometrial polyps, hyperplasia and cancer. In addition, it may be possible that
      tamoxifen increases the occurrence of uterine body tumours. We describe a rare
      case of a large endometrial polyp with sarcomatous stromal components in a 73
      year-old breast cancer patient treated daily with 20 mg of tamoxifen for four
      years. The glands of the polyp were lined by benign appearing epithelium. The
      polyp was twisted and protruded from a dilated cervix at the entrance of the
      vagina. The patient was treated by removal of the polyp and dilatation and
      curretage. A postoperative computed tomography scan showed many focal hypodense
      lesions in the hepatic lobes with a well-defined profile suggestive of metastatic
      disease and the patient was referred for combined chemotherapy. In conclusion, a
      case of a mesenchymal malignant neoplasm arising in the uterus of a breast cancer
      patient treated with tamoxifen is reported and its clinical, histological and
      immunohistochemical features are discussed. Also, the international literature is
      reviewed.

PMID- 14658607
TI  - Malignant ovarian germ cell tumors: analysis of 32 cases.
AB  - OBJECTIVE: In this study, some clinicopathologic characteristics and the outcome
      of patients with malignant ovarian germ cell tumors (MOGCT) were evaluated.
      MATERIALS AND METHODS: The clinical charts and pathologic reports of 32 patients
      with MOGCT treated at the Department of Obstetrics and Gynecology, and diagnosed
      at the Department of Pathology, Medical Faculty of Dicle University, Turkey from
      1983 to 1999 were reviewed. RESULTS: Thirteen patients (40.6%) had dysgerminoma,
      nine (28.1%) had immature teratoma (four grade 1, three grade 2, and two grade
      3), eight (25%) had endodermal sinus tumor, and two (6.3%) patients had mixed
      germ cell tumors. Site of involvement was unilateral in 30 (19 on the right and
      11 on the left) and bilateral in two. All patients underwent primary surgery and
      26 patients combination chemotherapy. There seemed to be a relationship between
      pathologic findings and clinical outcome, and MOGCT histologic types may affect
      the prognosis. CONCLUSION: Dysgerminoma had a better prognosis than the
      nondysgerminomatous group (p < 0.05). This study provides additional data in
      confirmation of previous reports that management of MOGCT with fertility
      preservation is safe.

PMID- 14658608
TI  - Primary carcinoid tumor of the ovary: a case report.
AB  - Primary ovarian carcinoid tumors are rare. A 47-year-old woman presented to our
      emergency room with lower abdominal pain. Physical examination, pelvic
      ultrasonographic evaluation and abdominal computed tomography revealed a 10-cm
      mass in the right ovary containing cystic and solid components, as well as
      calcifications typical of a dermoid cyst. At laparotomy, a smooth-surfaced, firm
      and mobile right adnexal mass with solid and cystic portions was detected.
      Initially, right salpingo-oophorectomy was performed. Frozen-section examination
      identified the mass as a sex cord stromal tumor containing a mature cystic
      teratoma. Based on this finding, total abdominal hysterectomy, left salpingo
      oophorectomy, omentectomy, appendectomy were performed, and the pelvic-paraaortic
      lymph nodes were also removed. All histological findings in the right ovary were
      similar to the features of cystic teratoma and trabecular carcinoid tumor.
      Examination of the resected lymphatic, omental, and appendiceal tissue indicated
      no tumoral invasion. The diagnosis was ovarian carcinoid Stage IA. Serum testing
      post-surgery revealed that the levels of cancer antigen (CA) 19-9 and CA125 were
      18.5 u/ml and 10.5 u/ml, respectively. The patient was discharged on
      postoperative day 5. The report describes the clinicopathologic and
      immunohistochemical features of a primary ovarian carcinoid that contained a
      mature cystic teratoma.

PMID- 14658609
TI  - Breast cancer metastatic to the vulva after local recurrence occurring on a
      rectus abdominis myocutaneous flap: a case report and review of the literature.
AB  - INTRODUCTION: Vulvar metastases are the third largest group of malignant tumors
      of the vulva. We report the tenth case of breast cancer vulvar metastases arising
      11 years after the primary diagnosis of breast ductal carcinoma and the first
      occurring eight years after a local recurrence on a rectus abdominis myocutaneous
      flap. CASE REPORT: A 49-year-old woman presented with a voluminous lump of the
      left labium majus and enlargement of the ipsilateral inguinal lymph nodes. The
      mass was removed together with the ipsilateral inguinal lymph nodes. Microscopic
      evaluation of the removed lump revealed massive carcinomatous infiltration. No in
      situ lesions nor normal breast tissue were identified. CONCLUSIONS: Unusual
      breast cancer metastases sites should not be ruled out. Our case differs from the
      preceding cases because this patient underwent plastic surgery with
      reconstruction of the breast with a rectus abdominis myocutaneous flap one year
      after mastectomy and developed a local recurrence three years thereafter. It can
      be hypothesized that lymphatic spread through newly formed lymphatics occurred.

PMID- 14658610
TI  - Laparoscopically assisted vaginal hysterectomy with bilateral salpingo
      oophorectomy due to endometrial cancer in a heart transplant recipient. A case
      report.
AB  - INTRODUCTION: Transplant recipients have a higher incidence of cancer compared
      with the general population. This increased risk is related to the intensity and
      chronicity of immunosuppression that these patients receive. In this report, we
      present a case of a heart transplant woman with endometrial cancer who was
      diagnosed six months after transplantation. CASE REPORT: A 49-year-old woman who
      had undergone a heart transplant was referred to our department in May 2002 for
      final treatment. The diagnosis of endometrial cancer was established on the basis
      of the histopathology findings of the fractional curettage. Her heart transplant
      had occurred six months before, as a result of idiopathic restrictive
      cardiomyopathy. The patient received triple immunosuppression with cyclosporin,
      azathioprine and prednisone and she displayed no signs of acute graft rejection
      features. Laparoscopically assisted vaginal hysterectomy with adnexa was
      performed without any complications. Duration of surgery was 85 minutes. The
      patient was operated on under general anesthesia and intraabdominal pressure was
      automatically maintained at 10 mmHg with a carbon dioxide insufflator (AESCULAP,
      Germany). Immunosuppressive therapy was continued without modification. The
      postoperative course was uncomplicated in our patient. No significant changes in
      heart rate or blood pressure were observed. The patient was discharged from the
      hospital on the 11th postoperative day. Microscopic appearance revealed Stage I
      endometrial cancer. The patient is in good physical condition with normal heart
      performance and without disease recurrence. CONCLUSION: In our opinion LAVH was a
      justifiable form of surgical management in the treatment of a heart transplant
      recipient with an early-stage endometrial cancer.

PMID- 14658611
TI  - Ovarian cyst as a pelvic mass in an infant.
AB  - Ovarian cysts in the neonate vary in size. Most of the cysts are asymtomatic but
      complications occur such as tortion, autoamputation or rupture. We report a case
      of a 3-month-old infant with an autoamputation ovarian cyst detected on a
      prenatal ultrasound scan (USS). Postnatal USS confirmed the presence of the cyst
      which failed to resolve after a period of conservative management and therefore
      surgical removal was performed.

PMID- 14658612
TI  - CA-125 elevation in malignant and nonmalignant conditions.

PMID- 14658613
TI  - Hyphenated techniques for elemental speciation in biological systems.

PMID- 14658614
TI  - Pore structure and sorption properties of silica aerogels studied by magnetic
      resonance imaging and pulsed-field gradient spectroscopy.
AB  - Magnetic resonance imaging (MRI) has provided direct visualization of gaseous
      xenon and methane in the void spaces of aerogels, offering unique information and
      insights into the pore structure and molecular diffusivities of occluded
      sorbates. Nuclear magnetic resonance (NMR) pulsed-field gradient (PFG) techniques
      were used to characterize exchange and diffusive motion of sorbed xenon gas at
      equilibrium. PFG measurements showed evidence of anisotropic diffusion; nominal
      self-diffusivity coefficients of xenon on the order of D = 10(-7) m2/s were
      determined. Based on a mathematical relationship for the restricted diffusion of
      gases in confined environments, an expression for estimating the mean free path
      was derived, from which the average pore size could be obtained from the
      extrapolated value of the diffusion coefficient to low xenon pressures.

PMID- 14658615
TI  - Ligand distributions in agarose particles as determined by confocal Raman
      spectroscopy and confocal scanning laser microscopy.
AB  - Confocal Raman spectroscopy and confocal scanning laser microscopy have been used
      to analyze ligand distributions within individual chromatographic adsorbent
      particles. Three different types of particles have been investigated. The first
      type was synthesized to have a uniform distribution of allyl groups, whereas the
      two others were designed to have a surface layer of sulphopropyl groups and cores
      containing allyl groups and dextran, respectively. With confocal Raman
      spectroscopy it was possible to follow the distribution of both the surface layer
      and the interior. The distribution of sulphopropyl groups was evaluated with both
      confocal scanning laser microscopy and confocal Raman spectroscopy, whereas the
      distributions of allyl groups and dextran were evaluated only with the latter
      method. The results from the confocal measurements showed the expected result
      with a uniform distribution of allyl groups in the first type of particle and
      surface layers of sulphopropyl groups and cores with dextran or allyl groups for
      the two others.

PMID- 14658616
TI  - On-the-fly fluorescence lifetime detection of humic substances in capillary
      electrophoresis.
AB  - On-the-fly fluorescence lifetime detection was investigated as a tool for
      studying humic substances in capillary zone electrophoresis (CZE). Humic
      substances are complex, heterogeneous mixtures of natural products that tend to
      migrate in a single, broad CZE peak. The intrinsic fluorescence lifetime of five
      humic substances from the International Humic Substances Society (IHSS) was
      monitored using excitation at 488 or 364 nm to produce intensity-lifetime
      electropherograms for each of the substances. Each frequency-domain lifetime
      measurement, collected at subsecond intervals during the CZE run, contains the
      equivalent of a complete decay profile. Lifetime analysis of each decay profile
      was used to construct a lifetime-resolved electropherogram for each lifetime
      component, from which the variation in relative intensity contributions of each
      lifetime across the broad CZE peak could be determined. Absorption spectra,
      fluorescence excitation-emission spectra, and lifetime profiles of batch
      solutions of the samples were determined as well. It was found that, whereas
      absorption and fluorescence spectral characteristics tended to discriminate
      between humic acids and fulvic acids, the batch solution lifetime profiles
      discriminated instead between samples from different sources, regardless of
      fraction. On-the-fly lifetime detection provided a more detailed view of the
      fluorescence decay of the samples, including greater resolution of lifetimes for
      two of the fulvic acids and greater discrimination among samples based on
      lifetime profiles across the CZE peaks.

PMID- 14658617
TI  - Carbon-thirteen cross-polarization magic angle spinning nuclear magnetic
      resonance and Fourier transform infrared studies of thermally modified wood
      exposed to brown and soft rot fungi.
AB  - Thermally modified wood has many technically interesting properties, such as
      increased dimensional stability, low equilibrium moisture content, and enhanced
      biological and weather resistance. This paper describes solid-state nuclear
      magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopic
      studies on the decay of heat-treated and untreated pine (Pinus sylvestris) by
      brown (Poria placenta) and soft rot fungi. Both techniques combined with
      multivariate data analysis proved to be powerful tools for the study of wood
      degradation by fungi. When untreated pine was exposed to brown or soft rot fungi,
      a drastic decay of the cell wall polysaccharides was observed. Brown rot fungus
      degraded mainly hemicelluloses while soft rot fungus attacked cellulose more
      extensively. The aromatic region of 13C cross-polarization magic angle spinning
      (CPMAS) NMR spectra revealed that the structure of lignin was also altered. New
      carboxylic structures were formed as a consequence of the decay. The increased
      biological resistance of pine wood heat-treated at >220 degrees C was observed in
      the 13C CPMAS NMR and IR spectra.

PMID- 14658618
TI  - Structural change of water with solutes and temperature up to 100 degrees C in
      aqueous solutions as revealed by attenuated total reflectance infrared
      spectroscopy.
AB  - The attenuated total reflectance infrared (ATR-IR) spectra of several aqueous
      solutions have been measured by using a newly developed heatable rod-type ATR
      cell. The OH stretching bands showed systematic change with increasing solute
      concentrations and these changes can be explained by four different OH components
      based on curve-fitting results. NaCl solutions show longer H-bond distance
      character, while carbonate solutions present shorter ones. The Na2CO3 1 M
      solution conserves this shorter H-bond nature up to 100 degrees C. On the other
      hand, the loose nature of NaCl solutions becomes less pronounced at higher
      temperatures because of the dissociation of pure water clusters. These in situ
      observations of water structures are generally in agreement with the expected
      nature of fluids within the earth.

PMID- 14658619
TI  - Fourier transform infrared attenuated total reflection and transmission spectra
      studied by dispersion analysis.
AB  - Fourier transform infrared transmission (FT-IR) and attenuated total reflection
      (ATR) spectra of water-ethanol mixtures are recorded and reconstructed thanks to
      a causal dispersion analysis technique. As expected, the Beer's law technique is
      an empirical approximate method that cannot account for complex spectral
      features. On the other hand, a rigorous analysis performed by using the
      theoretical optical paths for both experimental techniques and Gaussian
      dispersion analysis (GDA) allows the dielectric functions of the pure liquids to
      be calculated. Simulations of the whole mid-infrared spectra in the range 500
      4000 cm(-1) match the experimental data very well, whatever the water-ethanol
      mixtures. This method is a powerful tool to quantify such model mixtures and more
      generally could be the first step toward software for assistance to the FT-IR
      spectrum analysis.

PMID- 14658620
TI  - Simulation on wavelength-dependent complex refractive index of liquids obtained
      by phase retrieval from reflectance dip due to surface plasmon resonance.
AB  - A method for the calculation of the wavelength-dependent complex refractive index
      of absorbing liquid from reflectance in the vicinity of surface plasmon resonance
      (SPR) is presented. The calculation is based on the maximum entropy method (MEM).
      As an example, phase retrieval from a simulated SPR reflectance of a red colored
      liquid solution is carried out. It is proposed that MEM can be applied to
      wavelength-dependent complex refractive index assessment from reflectance of
      absorbing liquids in SPR measurement in wavelength scanning mode.

PMID- 14658621
TI  - Monitoring of itaconic acid hydrogenation in a trickle bed reactor using fiber
      optic coupled near-infrared spectroscopy.
AB  - Near-infrared (NIR) spectroscopy has been applied to determine the conversion of
      itaconic acid in the effluent stream of a trickle bed reactor. Hydrogenation of
      itaconic to methyl succinic acid was carried out, with the trickle bed operating
      in recycle mode. For the first time, NIR spectra of itaconic and methyl succinic
      acids in aqueous solution, and aqueous mixtures withdrawn from the reactor over a
      range of reaction times, have been recorded using a fiberoptic sampling probe.
      The infrared spectra displayed a clear isolated absorption band at a wavenumber
      of 6186 cm(-1) (wavelength 1.617 microm) resulting from the =C-H bonds of
      itaconic acid, which was found to decrease in intensity with increasing reaction
      time. The feature could be more clearly observed from plots of the first
      derivatives of the spectra. A partial least-squares (PLS) model was developed
      from the spectra of 13 reference samples and was used successfully to calculate
      the concentration of the two acids in the reactor effluent solution. Itaconic
      acid conversions of 23-29% were calculated after 360 min of reaction time. The
      potential of FT-NIR with fiber-optic sampling for remote monitoring of three
      phase catalytic reactors and validation of catalytic reactor models is
      highlighted in the paper.

PMID- 14658622
TI  - Improved methods for performing multivariate analysis and deriving background
      spectra in atmospheric open-path FT-IR monitoring.
AB  - Open-path Fourier transform infrared spectrometry (OP/FT-IR) may improve the
      temporal and spatial resolution in air pollutant measurements compared to
      conventional sampling methods. However, a successful OP/FT-IR operation requires
      an experienced analyst to resolve chemical interference as well as to derive a
      suitable background spectrum. The present study aims at developing a systematic
      method of handling the OP/FT-IR derived spectra for the measurement of
      photochemical oxidants and volatile organic compounds (VOCs) in urban areas. A
      classical least-squares (CLS) method, the most frequently used regression method
      in OP/FT-IR, is modified to constrain all the analyzed chemical species
      concentrations within a physically reasonable range. This new CLS method, named
      constrained CLS, may save the effort of predetermining the chemical species to be
      analyzed. A new background spectrum generation method is also introduced to more
      efficiently handle chemical interferences. Finally, CLS is shown to be prone to
      propagating errors in the case that a few data points contain a significant
      amount of error. The LI-norm minimization method reduces this error propagation
      to considerably increase the stability compared to CLS. The presently developed
      analysis software based on these approaches is compared with the other
      conventional CLS method using an artificially made single-beam spectrum as well
      as a field single-beam spectrum.

PMID- 14658623
TI  - Assessment of pareto calibration, stability, and wavelength selection.
AB  - Recent work has shown that ridge regression (RR) is Pareto to partial least
      squares (PLS) and principal component regression (PCR) when the variance
      indicator Euclidian norm of the regression coefficients, //p//, is plotted
      against the bias indicator root mean square error of calibration (RMSEC). Simplex
      optimization demonstrates that RR is Pareto for several other spectral data sets
      when //p// is used with RMSEC and the root mean square error of evaluation
      (RMSEE) as optimization criteria. From this investigation, it was observed that
      while RR is Pareto optimal, PLS and PCR harmonious models are near equivalent to
      harmonious RR models. Additionally, it was found that RR is Pareto robust, i.e.,
      models formed at one temperature were then used to predict samples at another
      temperature. Wavelength selection is commonly performed to improve analysis
      results such that bias indicators RMSEC, RMSEE, root mean square error of
      validation, or root mean square error of cross-validation decrease using a subset
      of wavelengths. Just as critical to an analysis of selected wavelengths is an
      assessment of variance. Using wavelengths deemed optimal in a previous study,
      this paper reports on the variance/bias tradeoff. An approach that forms the
      Pareto model with a Pareto wavelength subset is suggested.

PMID- 14658624
TI  - Practical algorithm for reducing convex spike noises on a spectrum.
AB  - Quantitative data analysis and high-sensitivity measurements by use of Raman and
      infrared spectroscopy often suffer from noisy spikes such as those due to cosmic
      rays and water vapor. Since these spikes are unidirectional and isolated, the
      conventional smoothing techniques do a poor job of removing them. However, a
      small modification can improve these smoothing techniques significantly. In this
      paper, we present a simple denoising technique for a single-scan spectrum that is
      corrupted by convex spikes. In general, the noisy spikes arising from cosmic rays
      or water vapor have a much narrower bandwidth compared with target "informative"
      bands in Raman and infrared spectra. This means that these noisy spikes can be
      separated from the target bands by means of the difference in the bandwidths. The
      proposed method employs the moving window averaging procedure to distinguish and
      separate the convex spike. The proposed algorithm allows us to take away the
      convex spikes from measured spectra without preparing multiply recorded spectra
      and (much) biasing the measured spectrum.

PMID- 14658625
TI  - Band centers and track finding for large two-dimensional infrared spectroscopic
      arrays.
AB  - An efficient two-dimensional (2D) peak-finding algorithm is proposed to find peak
      maps that specify the peak centers of all bands in two-dimensional arrays of time
      series infrared spectral data. The algorithm combines the second-derivative
      method with the intrinsic characteristics of 2D infrared reaction spectral data.
      Initially, the second-derivative method is used to detect all possible peak
      center positions, and then three criteria drawn from characteristics of 2D
      continuous spectral data are employed to filter peak positions. Four 2D peak maps
      are generated in a sequential order, with better and better approximations to the
      peak center positions being obtained in each. The 2D peak-finding algorithm has
      been successfully applied to both simulated spectra (to initially evaluate the
      algorithm) and then real 2D experimental spectra. The resulting peak maps exhibit
      very good estimates of the peak center positions. An ordering from the most
      significant to the least significant bands is obtained. The final peak maps can
      be used as starting parameters for various applications including the
      computationally intensive curve-fitting of time-series data.

PMID- 14658626
TI  - Computationally efficient curve-fitting procedure for large two-dimensional
      experimental infrared spectroscopic arrays using the Pearson VII model.
AB  - Extraction of quantitative information from large sets of sequential time-series
      spectra (two-dimensional, 2D, data) using a curve-fitting procedure is
      investigated. The difference between any experimental spectrum and any curve
      fitted spectrum is constructed in a least-squares manner and the Pearson VII
      model is selected as the general band-shape function for the infrared absorbance
      spectra. The starting point for the curve-fitting procedure is a 2D peak map.
      Next, an interior spectrum from the 2D array is chosen, initial guesses of the
      band parameters are provided by an initialization scheme, and curve fitting is
      performed. Once optimal values of the Pearson VII model band parameters are
      obtained from the starting spectrum in the 2D array, these are then used as
      reasonable and judicious initial guesses for subsequent curve fitting of the
      neighboring spectra in the time series. This increases computational efficiency
      enormously. By adjusting the band center positions for moving bands, and re
      optimizing each subsequent curve-fitting calculation to account for changing band
      shapes, the entire 2D array is rapidly and efficiently modeled. A 2D experimental
      spectroscopic time-series array from a homogeneous rhodium-catalyzed
      hydroformylation reaction was successfully curve fitted in this manner. The
      procedure holds considerable promise for the curve fitting of massive time-series
      spectroscopic data, such as that arising from on-line process monitoring of
      expensive value-added specialty chemical and pharmaceutical syntheses.

PMID- 14658627
TI  - Determination of trace metals in drinking water using solid-phase extraction
      disks and X-ray fluorescence spectrometry.
AB  - A convenient method is described for monitoring Cd, Ni, Cu, and Pb at trace
      levels in drinking water samples. These metals are preconcentrated on a chelating
      solid-phase extraction disk and then determined by X-ray fluorescence
      spectrometry. The method tolerates a wide pH range (pH 6-14) and a large amount
      of alkaline and alkaline earth elements. The preconcentration factor is well over
      1600, assuming a 1 L water sample volume. The limits of detection for Cd, Ni, Cu,
      and Pb are 3.8, 0.6, 0.4, and 0.3 ng/mL, respectively. These are well below the
      federal maximum contaminant level values, which are 5, 100, 1300, and 15 ng/mL,
      respectively. The proposed method has many advantages including ease of
      operation, multielement capability, nondestructiveness, high sensitivity, and
      relative cost efficiency. The solid-phase extraction step can be conducted in the
      field and then the disks can be mailed to a laboratory for the analysis,
      eliminating the cost of transporting large volumes of water samples. Furthermore,
      the color of the used extraction disk provides an initial estimate of the degree
      of contamination for some transition metals (for example, Ni and Cu). Thus, the
      overall cost for analysis of metals in drinking water can be minimized by
      implementing the method, and small water supply companies with limited budgets
      will be better able to comply with the Safe Drinking Water Act.

PMID- 14658628
TI  - Chemical imaging using microline laser ablation: performance comparison of
      Gaussian and flat top lasers.
AB  - In previous studies, the potential of a microline imaging arrangement for surface
      characterization of solid samples in air at atmospheric pressure using laser
      induced plasma spectrometry (LIPS) has been demonstrated. An improvement of this
      approach to obtain a uniform ablation along the microline focus that leads to a
      representative spatial distribution of elements on the sample surface is
      presented. For this purpose, the influence of beam energy distribution of two
      types of Nd:YAG pulsed lasers (a Gaussian laser and a flat top laser) on lateral
      resolution, intensity profiles of elements, chemical distribution maps, and
      plasma electron temperature has been investigated. As models of homogeneous and
      compositionally patterned samples, a stainless steel sample and a photovoltaic
      cell were chosen for this study. The results demonstrated that the Gaussian laser
      provides the best lateral resolution, but more redeposition at both sides of the
      microline crater, while the chemical maps obtained with the flat top laser
      matched with the distribution of the constituents of the sample surface.

PMID- 14658629
TI  - Chemometric approach to laser-induced breakdown analysis of gold alloys.

PMID- 14658630
TI  - Simultaneous determination of hydroxyl value, ethylene oxide content, and primary
      hydroxyl content for polyetherpolyol by means of near-infrared spectroscopy.

PMID- 14658631
TI  - Time-resolved Fourier transform infrared spectroscopic imaging.
AB  - Fourier transform infrared (FT-IR) imaging allows simultaneous spectral
      characterization of large spatial areas due to its multichannel detection
      advantage. The acquisition of large amounts of data in the multichannel
      configuration results, however, in a poor temporal resolution of sequentially
      acquired data sets, which limits the examination of dynamic processes to
      processes that have characteristic time scales of the order of minutes. Here, we
      introduce the concept and instrumental details of a time-resolved infrared
      spectroscopic imaging modality that permits the examination of repetitive dynamic
      processes whose half-lives are of the order of milli-seconds. As an illustration
      of this implementation of step-scan FT-IR imaging, we examine the molecular
      responses to external electric-field perturbations of a microscopically
      heterogeneous polymer-liquid crystal composite. Analysis of the spectroscopic
      data using conventional univariate and generalized two-dimensional (2D)
      correlation methods emphasizes an additional capability for accessing of
      simultaneous spatial and temporal chemical measurements of molecular dynamic
      processes.

PMID- 14658632
TI  - Development of a broadband picosecond infrared spectrometer and its incorporation
      into an existing ultrafast time-resolved resonance Raman, UV/visible, and
      fluorescence spectroscopic apparatus.
AB  - We have constructed a broadband ultrafast time-resolved infrared (TRIR)
      spectrometer and incorporated it into our existing time-resolved spectroscopy
      apparatus, thus creating a single instrument capable of performing the
      complementary techniques of femto-/picosecond time-resolved resonance Raman
      (TR3), fluorescence, and UV/visible/infrared transient absorption spectroscopy.
      The TRIR spectrometer employs broadband (150 fs, approximately 150 cm(-1) FWHM)
      mid-infrared probe and reference pulses (generated by difference frequency mixing
      of near-infrared pulses in type I AgGaS2), which are dispersed over two 64
      element linear infrared array detectors (HgCdTe). These are coupled via custom
      built data acquisition electronics to a personal computer for data processing.
      This data acquisition system performs signal handling on a shot-by-shot basis at
      the 1 kHz repetition rate of the pulsed laser system. The combination of real
      time signal processing and the ability to normalize each probe and reference
      pulse has enabled us to achieve a high sensitivity on the order of deltaOD
      approximately 10(-4) - 10(-5) with 1 min of acquisition time. We present
      preliminary picosecond TRIR studies using this spectrometer and also demonstrate
      how a combination of TRIR and TR3 spectroscopy can provide key information for
      the full elucidation of a photochemical process.

PMID- 14658633
TI  - New opportunities in micro- and macro-attenuated total reflection infrared
      spectroscopic imaging: spatial resolution and sampling versatility.
AB  - New opportunities exist to obtain chemical images using attenuated total
      reflection infrared (ATR-IR) spectroscopy. This paper shows the feasibility of
      obtaining FT-IR images with a spatial resolution of at least 3-4 microm using a
      Ge ATR objective coupled with an infrared microscope. The improved spatial
      resolution compared to FT-IR images obtained by the transmission method is due to
      the high refractive index of the ATR crystal, which gives a high numerical
      aperture and hence, a higher spatial resolution. FT-IR imaging with a
      conventional diamond ATR accessory has been investigated. This is the first time
      that FT-IR imaging is reported using such a versatile accessory based on a
      diamond ATR crystal. These results showed that a spatial resolution up to 13
      microm can be achieved without the use of infrared microscope objectives. One
      advantage of the diamond element is that it allows pressure to be applied and
      hence, good contact to be obtained over the whole field of view.

PMID- 14658634
TI  - Spectroscopic evaluation of the effect of a red microalgal polysaccharide on
      herpes-infected Vero cells.
AB  - The sulfated polysaccharide obtained from a species of red microalga has proved
      to be a potent antiviral agent against various members of the herpes family. In
      the present study, we used microscopic Fourier transform infrared spectroscopy
      (FT-IR) to investigate differences between normal cells, those infected with
      herpes viruses, and infected cells treated with red microalgal polysaccharide. FT
      IR enables the characterization of cell or tissue pathology based on
      characteristic molecular vibrational spectra of the cells. The advantage of
      microscopic FT-IR spectroscopy over conventional FT-IR spectroscopy is that it
      facilitates inspection of restricted regions of cell cultures or tissue. Our
      results showed significant spectral differences at early stages of infection
      between infected and noninfected cells, and between infected cells treated with
      the polysaccharide and those not treated. In infected cells, there was an
      impressive decrease in sugar content and a considerable increase in phosphate
      levels in conjunction with the infection progress. Our results also proved that
      sugars penetrated and accumulated inside cells treated with the red microalgal
      polysaccharide. These could have been sugar fragments of low molecular weight
      present in the polysaccharide solution, despite purification by dialysis. Such
      sugar accumulation might be responsible for a breakdown in the internal steps of
      the viral replication cycle.

PMID- 14658635
TI  - Stress-induced plasma volume change determined using plasma FT-IR spectra.
AB  - Our purpose was to determine the plasma-volume (PV) change induced by a physical
      stress independent of the metabolic events that may interfere with physiological
      fluid shifts in to and out of the intravascular space. Our methods included using
      178 exercise tests of varying duration and intensity for determination of PV
      change during exercise. Plasma Fourier transform infrared (FT-IR) spectra were
      used to compare hematocrit change to the total spectral area (4000-500 cm(-1))
      and the protein and albumin concentration changes induced by exercise. Our
      results showed that exercise induced a raise in protein (+10.4 +/- 3.1%) and
      albumin (+9.8 +/- 3.3%) concentrations that significantly correlated with PV
      change (14.1 +/- 5.2% of plasma volume; P = 0.05 with protein and albumin
      concentration changes). However, evolution of the total spectral area obtained
      from rest-plasma (524 +/- 21 a.u.) and exercise-plasma (611 +/- 26 a.u.; +14.1 +/
      4.8%) FT-IR spectra showed a higher correlation level with PV change (r = 0.98;
      P = 0.005; S(x/y) = 1.26 a.u.). It is our conclusion that although exercise
      induced changes in protein and albumin concentrations were found to correlate
      with PV change, the use of the total spectral area of the plasma FT-IR spectra
      allowed a more precise measurement of PV change.

PMID- 14658636
TI  - Determination of hydrocarbons using sapphire fibers coated with
      poly(dimethylsiloxane).
AB  - A poly(dimethylsiloxane) (PDMS) coated sapphire fiber has been investigated as a
      sensor for hydrocarbons (HCs) in the mid-infrared region around 3000 cm(-1). In
      order to optimize and predict sensor response, the diffusion behavior of the
      analytes into the PDMS preconcentration medium has been examined. A diffusion
      model based on Fickian diffusion was used to quantify diffusion. The model
      incorporated such factors as film thickness, refractive index of the polymer and
      the fiber core, and principal wavelength at which the analyte absorbs. A range of
      hydrocarbons, from hexane to pentadecane, was analyzed at 2930 cm(-1) using both
      fiber-coupled Fourier transform infrared spectroscopy and a modular prototype
      system. Diffusion coefficients were determined for these compounds and diffusion
      behavior examined and related to factors such as analyte polarity and molecular
      size. The diffusion coefficients were found to range from 6.41 x 10(-11) 5 x 10(
      12) to 5.25 x 10(-11) +/- 9 x 10(-13) cm2 s(-1) for hexane and pentadecane into a
      2.9 microm PDMS film, respectively. The diffusion model was also used to examine
      the effect of changing system parameters such as film thickness in order to
      characterize sensor response.

PMID- 14658637
TI  - Rapid, noninvasive quantitative determination of acyclovir in pharmaceutical
      solid dosage forms through their poly(vinyl chloride) blister package by solid
      state Fourier transform Raman spectroscopy.
AB  - Fourier transform (FT) Raman spectroscopy based on band intensity or band area
      measurements was used for the quantitative determination of acyclovir in
      pharmaceutical solid dosage forms through their poly(vinyl chloride) blister
      package. Univariate calibration using the bands observed at 1690, 1630, 1574,
      1482, 1181, 578, and 508 cm(-1) was found to be sufficient for the analysis.
      Calibration curves were linear, the correlation coefficients being 0.997-0.9993
      and 0.996-0.9991 for band intensity and band area measurements, respectively.
      Results obtained compare well, as indicated by the t-test, with those obtained by
      the current United States Pharmacopoeia (USP 24) and National Formulary (NF 19)
      method. Precision ranged from 0.7-4.5 and 0.4-4.0% RSD (n = 3) for band intensity
      and band area measurements, respectively. The developed nondestructive FT-Raman
      method is rapid, simple, and can be used for the on-line, real-time monitoring of
      acyclovir formulation production lines.

PMID- 14658638
TI  - Structural analysis of triacylglycerols and edible oils by near-infrared Fourier
      transform Raman spectroscopy.
AB  - Fourier transform Raman spectroscopy was employed for structural analysis of
      triacylglycerols and edible oils. Raman spectra sensitively reflected structural
      changes in oils. Even slight structural fluctuation between triacylglycerols and
      free fatty acids led to obvious differences in Raman bands as shown by C-O-C
      stretching from 800 to 1000 cm(-1) and the band at 1742 cm(-1). Structural
      difference in geometric isomers was easily distinguished as proved by C = C
      stretching at 1655 cm(-1) (cis) shifting to 1668 cm(-1) (trans) and by =C-H in
      plane bending at 1266 cm(-1) in cis disappearing in the trans isomer. Raman
      intensity at 1266, 1302, and 1655 cm(-1) changed concomitantly with the change of
      double-bond content in oils. It showed that FT-Raman was capable of precisly
      reflecting the content of double bonds in oils. A linear correlation with high
      consistency between the Raman intensity ratio (v1655/v1444) and the iodine value
      was obtained for commercial oils. Based on the results, FT-Raman spectroscopy
      proved itself a simple and rapid technique for oil analysis since each
      measurement could be directly completed in 3 min without any sample
      modifications.

PMID- 14658639
TI  - Optimizing detection sensitivity on surface-enhanced Raman scattering of
      transition-metal electrodes with confocal Raman microscopy.
AB  - Some points on how to improve the detection sensitivity of confocal Raman
      microscopy for the study of surface-enhanced Raman scattering (SERS) of
      transition-metal electrodes are discussed, including the careful design of the
      spectroelectrochemical cell, proper selection of the thickness of the solution
      layer, the binning of charge-coupled device (CCD) pixels, and appropriate setting
      of the notch filter. Various roughening methods for the Pt, Rh, Fe, Co, and Ni
      electrode surfaces have been introduced in order to obtain SERS-active surfaces.
      It has been shown that the appropriate roughening procedure and the optimizing
      performance of the confocal Raman microscope are the two most important factors
      to directly generate and observe SERS on net transition-metal electrodes.

PMID- 14658640
TI  - Use of a sample translation technique to minimize adverse effects of laser
      irradiation in surface-enhanced Raman spectrometry.
AB  - Surface-enhanced Raman spectroscopy (SERS) has proven to be a very powerful tool
      in the analysis of a wide range of compounds. However, continuous irradiation of
      the laser beam over the SERS substrate can promote the gross decomposition of the
      sample analytes and significantly broaden and diminish the intensities of
      observed spectral bands. In addition, the incident radiation can promote thermal
      or photolytic fragmentation of analytes, thereby altering the observable bands
      and possibly leading to a misinterpretation of analytical data. Finally, chemical
      or morphological changes in the SERS substrate are possible. This work presents
      the use of a sample translation technique (STT) as a means to minimize these
      adverse effects. By spinning the sample rapidly, the effective residence time of
      analytes and substrate within the irradiated zone is dramatically decreased
      without reduction of spectral acquisition time or the density of analyte in the
      zone. The technique is studied by acquiring SERS spectra of Naproxen USP,
      riboflavin, folic acid, Rhodamine 6G, and 4-aminothiophenol using silver islands
      on glass and silver-poly(dimethylsiloxane) composite substrates under various
      spinning and stationary conditions. In all cases, spectra show improvements upon
      spinning at laser powers as low as 4.2 (+/- 0.1) mW. Specific differences in the
      appearance of the spectra and the potential use of STT for improved SERS
      qualitative and quantitative determinations are presented.

PMID- 14658641
TI  - Monitoring the formation and decay of transient photosensitized intermediates
      using pump-probe UV resonance Raman spectroscopy. I: Self-modeling curve
      resolution.
AB  - Resolution of transient excited-state Raman scattering from ground-state and
      solvent bands is a challenging spectroscopic measurement since excited-state
      spectral features are often of low intensity, overlapping the dominant ground
      state and solvent bands. The Raman spectra of these intermediates can be
      resolved, however, by acquiring time-resolved data and using multidimensional
      data analysis methods. In the absence of a physical model describing the kinetic
      behavior of a reaction, resolution of the pure-component spectra from these data
      can be accomplished using self-modeling curve resolution, a factor analysis
      technique that relies on the correlation in the data along a changing composition
      dimension to resolve the component spectra. A two-laser UV pump-probe resonance
      enhanced Raman instrument was utilized to monitor the kinetics of amine quenching
      of excited-triplet states of benzophenone. The formation and decay of transient
      intermediates were monitored over time, from 15 ns to 100 micros. Factor analysis
      of the time-resolved spectral data identified three significant components in the
      data. The time-resolved intensities at each Raman wavenumber shift were projected
      onto the three significant eigenvectors, and least-squares criteria were
      developed to find the common plane in the space of the eigenvectors that includes
      the observed data. Within that plane, the three pure-component spectra were
      resolved using geometric criteria of convex hull analysis. The resolved spectra
      were found to arise from benzophenone excited-triplet states, diphenylketyl
      radicals, and the solvent and ground-state benzophenone.

PMID- 14658643
TI  - Multi-wavelength fluorescence-quenching model for determination of Cu2+
      conditional stability constants and ligand concentrations of fulvic acid.
AB  - In this work, a multi-wavelength model (MWM) is developed. It uses fluorescence
      bands in the fulvic acid (FA) spectrum that quench upon binding of inorganic Cu2+
      to FA. Quenching data at pH values of 5, 6, and 7 are placed in sets, containing
      fluorescence measures at select wavelengths versus added copper (CM). Intensity
      data of wavelength set 1 are obtained from 25 nm constant offset synchronous
      fluorescence spectra (SyF), in which are observed distinct peaks (lambda(ex) =
      415 nm, lambda(em) = 440 nm; and lambda(ex) = 471 nm, lambda(em) = 496 nm).
      Wavelength set 2 intensity data are obtained from the FA fluorescence excitation
      and emission maxima (lambda(ex) = 335 nm, lambda(em) = 450 nm; and X(ex) = 471
      nm, lambda(em) = 496 nm). Application of MWM shows that the multi-wavelength data
      sets characterize ligands of different binding strength (log K(x)) and
      concentration (C(Lx)). Corresponding to pH values of 5, 6, and 7, mean and
      standard deviation values for wavelength set 1 are log K(415/440) = 4.66 (0.12),
      5.03 (0.12), and 5.05 (0.08), log K(471/496) = 4.93 (0.06), 5.27 (0.11), and 5.39
      (0.09), C(415/440) = 3.1 (1.5), 10.9 (4.5), and 7.9 (3.9) microM, C(471/496) =
      14.3 (3.0), 1.7 (0.6), and 1.4 (0.5) microM. And for wavelength set 2, log
      K(335/450) = 4.50 (0.03), 4.96 (0.27), and 5.22 (0.08), log K(471/496) = 5.02
      (0.04), 5.42 (0.32), and 5.71 (0.09), C(335/450) = 8.8 (0.5), 21.9 (7.9), and
      18.7 (0.3) microM, C(471/496) = 21.0 (2.5), 7.17 (1.2), and 7.09 (0.3) micrpM.
      The ability of the 415/440 nm SyF transect to characterize the main excitation
      and emission maximum of FA at 335/440 nm is evaluated. Relatively low
      concentration values returned by the model for this transect (415/440 nm) suggest
      that it is not entirely illustrative of the maximum. The model predictive
      capability is verified at pH 6 with two fluorescing Cu2+ chelating organic
      compounds, L-tyrosine and salicylic acid. This test confirms that the model is
      capable of providing good estimates of equilibrium binding parameters from multi
      wavelength measurements of a mixed ligand system.

PMID- 14658642
TI  - Monitoring the formation and decay of transient photosensitized intermediates
      using pump-probe UV resonance Raman spectroscopy. II: Kinetic modeling and
      multidimensional least-squares analysis.
AB  - Analysis of transient excited-state Raman spectra is a challenging spectroscopic
      measurement since transient spectral features are often overlapped with dominant
      ground-state and solvent bands. In the previous manuscript, resolution of
      component Raman spectra from the time-resolved amine quenching of excited-triplet
      benzophenone was accomplished using self-modeling curve resolution, a model-free
      factor analysis technique that relies on correlation in the data along a changing
      composition dimension. The results are consistent with the production of
      diphenylketyl radicals by H-atom abstraction from the amine and subsequent free
      radical decay by recombination reactions. A kinetic model for this chemistry is
      developed in the present work, based on the observed Raman scattering data and
      the structures of product species confirmed by mass spectral analysis. The model
      is applied to the analysis of the time-dependent Raman scattering data using
      multidimensional least-squares methods, and it yielded well-resolved spectra of
      benzophenone excited-triplet states, diphenyl ketyl radical, and the solvent and
      ground-state precursors. The best-fit kinetic parameters agree well with the time
      dependent triplet-state and ketyl-radical concentration profiles.

PMID- 14658644
TI  - Multiphoton ionization mass spectrometry of chlorophenols as indicators for
      dioxins.
AB  - Mono-, di- and trichlorophenols were measured using resonance-enhanced
      multiphoton ionization mass spectrometry (MPI-MS) combined with supersonic jet
      (SSJ) or effusive molecular beam (EMB) spectrometry. All mono- and
      dichlorophenols, except 2,6-dichlorophenol, provided sharp and structured MPI
      spectra for the S1 <-- S0 transition. Selectivity and sensitivity were both
      enhanced when SSJ spectrometry was used, compared with EMB spectrometry, because
      of a narrower linewidth in the MPI spectrum, given by molecular cooling by
      supersonic jet expansion. The ionization efficiency decreased with increasing
      number of chlorine substituents for the chlorophenols, since they have shorter
      excited-state lifetimes and require three photons for ionization. Some of the
      chlorophenols, which are toxic themselves, have the potential for use as
      indicators for analysis of polychlorinated dibenzo-p-dioxin/dibenzofurans in flue
      gases emitted from an incinerator.

PMID- 14658645
TI  - Sugar interaction with metals in aqueous solution: indirect determination from
      infrared and direct determination from nuclear magnetic resonance spectroscopy.
AB  - In this article, mid-infrared Fourier transform (Mid-FT-IR) and carbon thirteen
      nuclear magnetic resonance (13C NMR) spectroscopy have been used to determine
      possible interactions between sucrose and various alkali or alkaline earth metals
      in aqueous solution. In the presence of these metals, significant shifts in the
      absorption bands of sucrose were noted by mid-FT-IR coupled with principal
      component analysis (PCA). These shifts were explained on the basis of weakening
      of the H-bond network between sucrose and water and possible interactions between
      sucrose and the metal ion. Factorial maps were established and the spectral
      patterns obtained show that these interactions vary according to the nature of
      the metal ion. 13C NMR analysis showed that the carbon atoms of sucrose undergo
      shielding or deshielding in the presence of metal ions in aqueous solutions. Two
      factors were invoked to account for the variation of chemical shifts: the rupture
      of hydrogen bonds due to hydration of the metal ion and the possible coordination
      of the metal ion to the oxygen atoms of sucrose.

PMID- 14658646
TI  - Determining water content in human nails with a portable near-infrared
      spectrometer.
AB  - The water content of human nail plates was determined using a portable near
      infrared (NIR) spectrometer with an InGaAs photodiode array detector. NIR diffuse
      reflectance (DR) spectra were collected from 108 cut nail plates with different
      relative humidity and in vivo from fingernails. Partial least-squares (PLS)
      regression was applied to the NIR spectra in the 1115-1645 nm region to develop
      calibration models that determine the water content in the cut nail plates and
      fingernails. A good correlation was obtained between the NIR spectra and the
      water content measured by nuclear magnetic resonance (NMR) for the NIR
      measurement of both cut nail plates and fingernails. The results indicate that
      the water content in the nails can be determined very rapidly (1 s) by means of
      the portable NIR spectrometer and PLS regression.

PMID- 14658647
TI  - Simultaneous chemical separation and surface-enhanced Raman spectral detection
      using silver-doped sol-gels.

PMID- 14658648
TI  - Laser-enhanced ionization with avalanche amplification: detection of cesium at
      fg/mL levels.
AB  - The avalanche amplification of the laser-enhanced ionization signal of Cs atoms
      in a flame has been studied. Ionization of Cs atoms, enhanced by two-step
      excitation, was detected in hydrogen and propane flames. By employing the effect
      of avalanche amplification of electrons, high signal-to-noise ratio
      (approximately 10(4)) was obtained for a 100 ppt Cs solution. The extrapolated
      limit of detection was 30 fg/mL (ppq).

PMID- 14658649
TI  - Potential for using a digital micromirror device as a signal multiplexer in
      visible spectroscopy.
AB  - A digital micromirror device (DMD) was tested to demonstrate its potential as a
      multiplexing device for the simultaneous detection of visible electromagnetic
      radiation. Using a Visual Basic program, four sections of the DMD were
      illuminated by a light source and each region of mirrors was modulated at
      different low frequencies (14.92, 20.00, 25.00, and 34.48 Hz). A time-domain,
      multiplexed signal was collected from the sectors and a Fourier transform was
      performed on these data. The resulting frequency-domain spectrum showed that
      signal intensities correlated well with what was expected. Three different times
      were used to establish the best frequency resolution. Using this calculated
      frequency resolution, a 16 s scan could allow simultaneous detection of up to 240
      emission/absorption wavelengths. Data collected also shows the selectivity of
      micromirror regions and the ability to choose specific regions of the micromirror
      plane, which could be valuable for a number of spectroscopic techniques.

PMID- 14658650
TI  - Laser plasma spectroscopy of Al-Cu-Fe quasicrystal an d alloy.
AB  - Electron number density and temperature were determined from laser-induced
      plasmas produced by irradiating Al-Cu-Fe targets of a quasicrystal and of an
      alloy of similar composition. The Al(I) atomic emission spectra of the two
      systems were measured as a function of the distance from the target and of the
      time delay after laser irradiation. Differences of plasma characteristics were
      observed for laser ablation of quasicrystal and alloy targets, and the results
      were interpreted on the basis of different plasma formation mechanisms for the
      two systems.

PMID- 14658651
TI  - Mars analysis by laser-induced breakdown spectroscopy (MALIS): influence of mars
      atmosphere on plasma emission and study of factors influencing plasma emission
      with the use of doehlert designs.
AB  - A project called MALIS (Mars Analysis by Laser-Induced breakdown Spectroscopy) is
      under progress to perform in situ analysis of Mars soils and rocks. This paper
      reports on the behavior of plasma in Martian conditions, i.e., in a CO2
      atmosphere at pressures between 5 and 12 mbar. Plasma expansion and lifetime have
      been studied in order to compare plasma evolution under standard conditions (air
      at atmospheric pressure) and in a Mars atmosphere. We have shown that the Mars
      environment favors plasma expansion and lifetime. The second part of the study
      concerns optimization of the emission signal from the plasma. An original
      approach has been chosen, as we used a Doehlert design for the first time in
      laser-induced breakdown spectroscopy (LIBS). The best conditions obtained are for
      a laser wavelength of 1064 nm with the maximum energy available due to space
      limitations, which is 40 mJ at 15 Hz. The other factors studied are delay, angle
      of incidence, and CO2 pressure. We have shown that these factors do not have the
      same influence depending on which spectroscopic line is used, i.e., the atomic
      line or the ionic line.

PMID- 14658652
TI  - Study of fitting algorithms applied to simultaneous analysis of large numbers of
      peaks in gamma-ray spectra.
AB  - In this paper several nonlinear fitting algorithms without matrix inversion are
      proposed and investigated. The fitting algorithms represent an integral part of
      the analysis procedure, allowing us to simultaneously process large numbers of
      peaks in large blocks of data. The algorithms were applied to the analysis of
      both one-dimensional as well as two-fold coincidence gamma-ray spectra. The
      properties of the proposed methods and the suitability of employing the
      appropriate algorithms to different kinds of gamma-ray spectra were studied.

PMID- 14658653
TI  - Multi-wavelength raman imaging using a small-diameter image guide with a
      dimension-reduction imaging array.
AB  - A commercially available fiber-optic Raman probe was modified for high-resolution
      spectral Raman imaging using a 350 microm diameter optical fiber image guide
      coupled to a dimension-reduction imaging array (DRIA). The DRIA comprised 672
      optical fibers, arranged as a square array (21 x 32 fibers) on one end and a
      linear array (672 x 1 fibers) on the other. An imaging spectrograph was used with
      the DRIA to acquire multi-wavelength Raman images from -250 to 1800 cm(-1) at a
      spectral resolution of approximately 5 cm(-1). The utility of this technique for
      in situ and remote Raman imaging is demonstrated by monitoring the polymerization
      of a model polymer, dibromostyrene (DBS), while simultaneously measuring the
      Raman Stokes/ anti-Stokes ratio as a function of sample heating time, over a
      sample area of approximately 4 x 1.6 mm.

PMID- 14658654
TI  - Raman spectroscopy as a tool for measuring mutual-diffusion coefficients in
      hydrogels.
AB  - Raman spectroscopy has been exploited to characterize the diffusion properties of
      solutes in hydrogels. Raman active vibrations were used as intrinsic probes of
      the solute concentration along gel cylinders. The resulting one-dimensional
      solute distribution, characterized as a function of both time and space, could be
      analyzed with a model based on Fick's diffusion law, and the mutual-diffusion
      coefficient (Dm) was then determined. To illustrate the potential of this
      approach, we measured the Dm of two polyethylene glycols (PEG) in Ca-alginate
      gels. In this case, the intensity of the CH stretching band was used to obtain
      the concentration profiles of PEGs, whereas the OH stretching band of water was
      used as an internal intensity standard. In addition to providing a
      straightforward approach to measuring diffusion coefficients, the Raman profile
      analysis provides information relative to the accessibility of gels to large
      molecules. As an example, it was found that the PEG penetration in Ca-alginate
      gels was restricted, a phenomenon that was dependent on PEG size. The Raman
      technique presented here effectively characterizes transport properties of
      solutes in gels, and such characterization is required for developing several
      technical applications of gels, such as their use as materials for controlled
      release of drugs.

PMID- 14658655
TI  - Effects of particle size and laser-induced heating on the Raman spectra of alpha
      quartz grains.
AB  - Raman spectra of alpha-quartz (Qz) grains of various size (250 microm to < 11
      microm) and arrangement (individual and aggregated) have been investigated with a
      combination of confocal Raman and micro-Raman systems. Frequency downshift and
      line broadening of the 464 cm(-1), v,(Si-O-Si) band are observed in the smallest
      size group (< 11 microm, both individual grains and aggregates) because of laser
      induced heating and are used to estimate the temperature of the sampled region.
      The intensity ratio of the anti-Stokes to Stokes Raman lines is also used to
      estimate the vibrational temperature of the samples under different excitation
      power. The degree of laser-induced heating is more noticeable in the aggregates
      than in the individual grains with the use of medium-level laser excitation (< or
      = 150 mW). Heating diminishes with increasing grain size, and it can only be
      detected in grain aggregates between 11 and 20 microm in diameter using 150 mW
      excitation. Intensity studies of the v(s)(Si-O-Si) band using individual grains
      show no noticeable signs of grain size effects. However, grain size effects
      become an important factor in the study of aggregates in which spectral intensity
      diminishes with respect to decreasing grain size.

PMID- 14658656
TI  - Exploitation of FRiedel-Crafts acylation as a color derivatizing reaction for
      terpene and lipids analyses.
AB  - Rapid Friedel-Crafts chromogenic acylations of alkene groups at ambient
      temperatures are shown to be successful selective procedures for discriminating
      among a group of natural products, twelve of which are structurally related low
      molecular weight hydrocarbons that include nine terpenoids, and nineteen
      unsaturated and polyunsaturated fatty acid esters. The procedure has all the
      properties needed of a rapid, routine assay for use as a quality control test
      reagent for standard reference materials and natural oils, for on-line analyses
      during their commercial processing, and the potential for applications in the
      analyses of multicomponent mixtures without the need for prior separation.

PMID- 14658657
TI  - Friedel-Crafts acylation as a quality control assay for steroids.
AB  - The rapid Friedel-Crafts chromogenic acylation of alkene groups at ambient
      temperatures using a 25:1 mixture of 98% acetyl chloride and 70% perchloric acid
      is shown to have all the properties needed to serve as a potential quality
      control reagent that can be used to routinely discriminate among steroid analogs.
      Although ostensibly a non-selective reagent, from these and prior applications in
      terpenes and polyunsaturated acid esters, it is seen that the reaction is capable
      of discriminating bewteen geometric isomers and even enantiomers. The selectivity
      towards acylation of the alpha- over the beta-position at C-17 makes the method
      adaptable to screening for anabolic steroids. Reactions at that position produce
      the more unusual results, including a positive color reaction for alpha
      methyltestosterone even though there is no alkene functional group in the
      vicinity of C-17. For molecules with more than one alkene, concurrent acylations
      are independent one from the other and, in the absence of any interferences,
      their spectral properties are found to be additive.

PMID- 14658658
TI  - Determination of enantiomeric excess using the ultraviolet-circular dichroism and
      the high-performance liquid chromatography-circular dichroism methods.
AB  - Two useful numerical methods using ultraviolet (UV) and circular dichroism (CD)
      spectroscopies are proposed to determine enantiomeric excess (e.e). An algorithm
      is also proposed to generate self-consistent pure R and S enantiomer reference
      spectra. After all pure reference spectra are generated, a simulated annealing
      algorithm is applied to minimize the mismatch between the experimental spectra
      and the spectra after a least-squares fit. Optimal factors for R and S
      enantiomers are then used to determine e.e. The ultraviolet-circular dichroism
      (UV-CD) method uses the combined UV and CD spectra in a composite form, while the
      high-performance liquid chromatography (HPLC)-CD method only employs the CD
      spectra with the total concentrations of R plus S enantiomers provided by HPLC
      using a non-chiral stationary phase. Both methods were successfully tested on
      mixtures with known composition and then applied to real experimental data
      (unknown compositions). Compared with the UV-CD method, the results show that
      excellent results are more readily obtained using the HPLC-CD method. With the
      systems studied, the latter usually provided outstanding estimations of e.e with
      low error percentages.

PMID- 14658659
TI  - Investigation of asphaltene association by front-face fluorescence spectroscopy.
AB  - The tendency of asphaltenes to aggregate and form clusters in solvents was
      studied by fluorescence spectroscopy. This was done by evaluating the relative
      fluorescence quantum yield of asphaltenes diluted at several concentrations in
      toluene and by studying the changes in the fluorescence spectra of asphaltene
      solutions as the composition of the solvent, toluene and cyclohexane, is changed.
      The asphaltene fraction (heptane insoluble) was collected from a Brazilian heavy
      crude oil, and solutions of this material varying from 0.016 g/L up to 10 g/L
      were prepared in toluene. Front-face emission spectra were obtained in two
      wavelength ranges, from 310 to 710 nm, excited at 300 nm (short range), and from
      410 to 710 nm, excited at 400 nm (long range). Severe quenching was observed at
      concentrations above about 0.1 g/L. Stern-Volmer plots (reciprocal of quantum
      yield against concentration) exhibited nonlinear, downward-curved behavior,
      indicating that a more complex suppression mechanism, probably influenced by the
      association of the asphaltene molecules, is taking place. The same asphaltenes
      were dissolved (0.1 g/L) in binary mixtures of toluene and cyclohexane, and
      emission spectra in both the short range and long range were obtained.
      Fluorescence was progressively quenched at longer wavelengths of the spectra as
      the proportion of cyclohexane in the solvent grew. Cyclohexane, a poor asphaltene
      solvent, is probably inducing static quenching through association of
      asphaltenes.

PMID- 14658660
TI  - Multi-wavelength mid-infrared micro-spectral imaging using semiconductor lasers.
AB  - Infrared (IR, 3-12-microm) microscopic spectral imaging is an important
      analytical technique. Many current instruments employ thermal IR light sources,
      which suffer the problem of low brightness and high noise. This paper evaluates
      the system engineering merit in using semiconductor lasers, which offer orders-of
      magnitude-higher power, brightness, and lower noise. A microscopic spectral
      imaging system using semiconductor lasers (quantum cascade) as illuminators, and
      focal plane array detectors demonstrated a high signal-to-noise ratio (> 20 dB)
      at video frame rate for a large illuminated area. The comparative advantages of
      laser vs. thermal light source are analyzed and demonstrated. Microscopic
      spectral imaging with fixed-wavelength and tunable lasers of 4.6-, 5.1-, 6-, and
      9.3-microm wavelength was applied to a number of representative samples that
      consist of biological tissues (plant and animal), solid material (a stack of
      laminated polymers), and liquid chemical (benzene). Transmission spectral images
      with approximately 30-dB dynamic range were obtained with clear evidence of
      spectral features for different samples. The potential of more advanced systems
      with a wide coverage of spectral bands is discussed.

PMID- 14658661
TI  - Sol-gel-coated mid-infrared fiber-optic sensors.
AB  - Application of organically modified sol-gels as novel recognition membranes for
      mid-infrared fiber-optic sensors is demonstrated for the first time by in situ
      detection of nitro-based aromatic compounds in aqueous media. Sol-gels were
      prepared by acid- and base-catalyzed copolymerization of alkyltrimethoxysiloxanes
      and applied onto the surface of silver halide (AgCl(0.3)Br(0.7)) fibers by drip
      coating. The coating process was monitored in situ using Fourier transform
      infrared (FT-IR) spectroscopy. Homogeneity of the layers was analyzed by scanning
      electron microscopy. Sol-gel-coated evanescent held sensors were investigated
      with respect to their capacity to suppress interfering water background
      absorptions, repeatability of dissolved analyte enrichment, and sensor response
      time. Nitrobenzene and parathion are the investigated analytes; figures of merit
      are derived from calibration curves determined to assess sensitivity and
      reproducibility of the developed sensor system. It can be concluded that sol-gel
      coated infrared fiber-optic sensors enable reproducible detection of nitro-based
      aromatic compounds in the low ppm concentration range. Due to wide flexibility in
      tuning chemical properties of sol-gel films along with superior mechanical and
      chemical stability, organically modified sol-gels represent highly interesting
      coating materials for mid-infrared sensing applications.

PMID- 14658662
TI  - Specific interactions study in complexes of poly(mono-n-alkyl itaconates) with
      tertiary polyamides.
AB  - This paper reports an FT-IR study of blends of poly(mono-n-alkyl itaconates) with
      poly(N,N-dimethylacrylamide) (PDMA) and poly(ethyloxazoline) (PEOX). Strong
      hydrogen bonding has been found, and both polybases have shown similar acceptor
      strengths. Derivative techniques show asymmetric profiles for the free carbonyl
      band of the polybases, resulting in shifted band locations. The extent of the
      interassociation has been estimated by spectral curve fitting of the polybase
      carbonyl band. The results show that the interaction degree in blends with PEOX
      does not depend on the length of the poly(monoalkyl itaconate) side group, while
      an inter-associating ability loss is observed in blends with PDMA as the side
      group size of the polyacid increases. This different behavior is attributed to
      the greater interspacing between vicinal carbonyl groups in PEOX. This band shows
      conformational sensitivity and reflects the conformational changes that occur as
      the steric hindrances present in the medium (due to the bulky side groups of the
      polyacids) increase.

PMID- 14658663
TI  - FT-IR spectroscopic analysis of rainbow trout liver exposed to nonylphenol.
AB  - Nonylphenol (NP) is a biodegradation product of nonylphenol ethoxylates (NPEs)
      belonging to the alkylphenol ethoxylates (APEs) group. APEs are widely used
      nonionic surfactants in detergents, herbicides, pesticides, paints, and
      cosmetics. The present work investigates the effects of NP on rainbow trout
      (Oncorhynchus mykiss) livers at the molecular level using Fourier transform
      infrared (FT-IR) spectroscopy. The FT-IR spectra revealed dramatic differences
      between the NP-treated and control tissues, which mainly indicated that the level
      of triglycerides increased, the lipid order increased, and the protein
      concentration decreased in the treated samples. Moreover, it was also found that
      glycogen levels significantly decreased and the relative content of nucleic acids
      increased in NP-treated fish. The 17beta-Estradiol-treated fish liver spectra
      were found to be quite similar to those of NP-treated fish. All these results
      implied that rainbow trout may offer considerable promise to be used as a
      bioindicator for NP in the future.

PMID- 14658664
TI  - FT-IR study of a chemically amplified resist for X-ray lithography.
AB  - Microelectronic devices for future applications demand lithographic performance
      that falls within the 0.10 microm region and below. Chemically amplified resists
      (CARs), such as the positive tone commercial UVIII resist, offer a substantial
      gain in sensitivity, resolution, and process efficiency in deep ultraviolet, e
      beam, and X-ray lithographies. In this work, the UVIII resist is characterized
      for X-ray lithographic applications by studying the "deprotection" or acid
      generation-diffusion process of the resist under different conditions of post
      exposure bake (PEB) temperature and time, and of X-ray exposure dose. The X-ray
      irradiation from a copper anode at a wavelength of 1.33 nm was at an intensity of
      30 microW/cm2 on the resist surface. The deprotection process of the resist
      during PEB was accurately monitored by using Fourier transform infrared (FT-IR)
      spectroscopy. The infrared absorption peaks at 1151, 1369, and 2977 cm(-1) in the
      spectrum of the UVIII resist were found to be useful indicators for the
      completion of deprotection. Results of the experiments showed that the
      performance of UVIII could be optimized at the PEB temperature of 140 degrees C,
      a time of 2 min, and X-ray exposure dose of 12 mJ/cm2. The change in resist
      thickness after PEB was also measured. The results were confirmed by scanning
      electron microscopy (SEM) in which a test structure as small as 0.12 microm was
      obtained in a 1-microm-thick UVIII resist layer.

PMID- 14658665
TI  - New approach to generalized two-dimensional correlation spectroscopy. IV:
      eigenvalue manipulation transformation (EMT) for partial attenuation of dominant
      factors.
AB  - This paper extends our previous work on the potential of eigenvalue manipulating
      transformation (EMT) of a data matrix for spectral selectivity enhancement in two
      dimensional (2D) correlation analysis. EMT operation by uniformly lowering the
      power of a set of eigenvalues associated with the original data exaggerates the
      information content of minor principal components and reduces that of major
      principal components. Thus, much more subtle differences of spectral behavior for
      each component are now highlighted. Similarly, the selective truncation of
      dominant principal component (PC) factors to bring up the subtle contributions of
      minor factors is also considered. The EMT-reconstructed data matrix where power
      parameter m is negative greatly reduces the contribution of the first PC. Hybrid
      models for the attenuation of the contribution of the first PC are discussed.
      Synchronous 2D correlation spectra from PC1-attenuated data matrix A** obtained
      by varying the value of the attenuation parameter k show a much more profound
      effect than asynchronous 2D correlation spectra. As the value of k is increased,
      features of 2D correlation spectra start looking very much like those from the
      principle component analysis (PCA)-reconstructed data with only the second and
      third PCs and from the EMT-reconstructed data matrix where the power parameter m
      is negative.

PMID- 14658666
TI  - Spectral code index (SPECOIND): a general infrared spectral database search
      method.
AB  - A new spectral code that can be used by Relational Database Management Systems
      (RDBMS) as an index for infrared (IR) spectra searches in Relational Database
      (RDB) is presented and its suitability is evaluated. Spectral codes are
      constructed for all spectra in the database as the spectral indexes and three
      query strings are created with the same theory used for the creation of the index
      code for the query spectrum. Some effects of parameters used to create index
      strings and query strings are discussed. All spectral searches are accomplished
      in structured query language (SQL) approach and the utilization examples of SQL
      have been shown. The sequential application of this procedure can reduce the
      original library of about 18000 spectra to a few spectra that can be used as
      references for subsequent detailed comparison. The software developed for the
      proposed system is particularly suitable for spectral search and structure
      interpretation.

PMID- 14658667
TI  - Analysis of single bacterial spores by micro-Raman spectroscopy.

PMID- 14658668
TI  - Adsorption of copper tetra-t-butylphthalocyanine aggregates from alcoholic
      solution onto glass observed by optical waveguide spectroscopy.

PMID- 14658669
TI  - TEA-CO2 laser-induced shock wave plasma modulated by wires and needles placed in
      front of the target at low pressure.

PMID- 14658670
TI  - Multivariate curve resolution in the analysis of vibrational spectroscopy data
      files.

PMID- 14658671
TI  - Study of complexation in methanol/water mixtures by infrared and Raman
      spectroscopy and multivariate curve resolution-alternating least-squares
      analysis.
AB  - The structure of the mobile phase in liquid chromatography plays an important
      role in the determination of retention behavior on reversed-phase stationary
      materials. One of the most commonly employed mobile phases is a mixture of
      methanol and water. In this work, infrared and Raman spectroscopic methods were
      used to investigate the structure of species formed in methanol/water mixtures.
      Chemometric methods using multivariate curve resolution by alternating least
      squares analysis were used to resolve the overlapped spectra and to determine
      concentration profiles as a function of composition. The results showed that the
      structure of these mixtures could be described by a mixture model consisting of
      four species, namely, methanol, water, and two complexes, methanol/water (1:1)
      and methanol/water (1:4). The spectral frequencies and concentration profiles
      found from the Raman and infrared measurements were consistent with one another
      and with theoretical calculations.

PMID- 14658672
TI  - Spectral pattern recognition of in situ FT-IR spectroscopic reaction data using
      minimization of entropy and spectral similarity (MESS): application to the
      homogeneous rhodium catalyzed hydroformylation of isoprene.
AB  - An improved algorithm using minimization of entropy and spectral similarity
      (MESS) was tested to recover pure component spectra from in situ experimental
      Fourier transform infrared (FT-IR) reaction spectral data, which were collected
      from a homogeneous rhodium catalyzed hydroformylation of isoprene. The
      experimental spectra are complicated and highly overlapping because of the
      presence of multiple intermediate products in this reaction system. The
      traditional entropy minimization method fails to resolve real reaction mixture
      spectra, but MESS can successfully reconstruct pure component spectra of unknown
      intermediate products for real reaction systems by the addition of minimization
      of spectral similarity. The quantitative measure of spectral similarity between
      two spectra was given by their inner products. The results indicate that MESS is
      a stable and useful algorithm for spectral pattern recognition of highly
      overlapped experimental reaction spectra. Comparison is also made between MESS,
      entropy minimization, simple-to-use interactive self-modeling mixture analysis
      (SIMPLISMA), interactive principle component analysis (IPCA), and orthogonal
      projection approach-alternating least squares (OPA-ALS).

PMID- 14658673
TI  - Electric-field-induced reorientation of liquid crystalline p-cyanophenyl-p-n
      alkylbenzoates: a time-resolved study by fourier transform infrared transmission
      and attenuated total reflection spectroscopy.
AB  - Time-resolved polarization Fourier transform infrared (FT-IR) transmission and
      attenuated total reflection (ATR) spectroscopy were applied to investigate the
      reorientation phenomena of the three members of the homologous series of nematic
      liquid crystalline p-cyanophenyl-p-n-alkylbenzoates 6CPB, 7CPB, and 10CPB under
      the external perturbation of an electric field. In conjunction with a newly
      constructed measurement cell, this method allowed us to differentiate the
      response of the LC system in the surface layer and in the bulk of the cell at
      different temperatures and voltages. The relaxation time of the LC molecules
      close to the wall of the cell was found to be shorter than in the bulk. However,
      at a field strength of 7 V, the initial orientation in the bulk preceeds the
      analogous process in the surface region.

PMID- 14658674
TI  - Attenuated total reflection surface-enhanced infrared absorption spectroscopy of
      carboxyl terminated self-assembled monolayers on gold.
AB  - A new recipe for surface-enhanced infrared absorption (SEIRA) active island Au
      films with improved adhesion in aqueous solution, low resistivity, and
      enhancement of the infrared (IR) absorption of about 300 was developed. The Au
      films prepared were utilized in studies of the ionization of self-assembled
      monolayers of 11-mercaptoundecanoic acid in Na2SO4 aqueous solutions by
      attenuated total reflection surface-enhanced infrared absorption (ATR-SEIRA)
      spectroscopy. It was found that the carboxyl end groups of the self-assembled
      monolayer turn into carboxylate anions on going from anodic to cathodic
      potentials or from acidic to alkaline pH. The water molecules close to the self
      assembled monolayer in acidic solutions or at anodic potentials are
      preferentially aligned with their dipole moments parallel to the interface. This
      type of alignment can be ascribed to the dipole-dipole interaction between the
      carboxyl groups and the water molecules. On the other hand, in alkaline solutions
      or at cathodic potentials the structure of water close to the self-assembled
      monolayer is essentially bulk-like, with randomly oriented water molecules. This
      observation suggests that in alkaline solutions or at cathodic potentials the
      charge of the carboxylate anions is almost completely compensated for by strongly
      adsorbed counter cations. As a result, the electric field close to the surface of
      the ionized self-assembled monolayer is weak and has little influence on the
      orientation and hydrogen bonding of the water molecules.

PMID- 14658675
TI  - Monitoring decay of black gum wood (Nyssa sylvatica) during growth of the
      shiitake mushroom (Lentinula edodes) using diffuse reflectance infrared
      spectroscopy.
AB  - Abstract diffuse reflectance infrared spectroscopy (DRIFT) and elemental analysis
      were employed to monitor biodegradation of black gum wood (Nyssa sylvatica)
      during growth of the shiitake mushroom (Lentinula edodes). Black gum was decayed
      for up to 4.3 years by L. edodes, during which time it was sampled at 19, 31, and
      52 months. Biodegraded woods displayed increased % O (w/w) and decreased % C
      (w/w) relative to the undecayed control. The DRIFT spectra of decayed black gum
      showed a decrease in relative intensity of absorption bands at 1735 cm(-1)
      assigned to carboxyl functional groups from xylans and an increase in the
      absorption band at 1640 cm(-1) assigned to conjugated carbonyl groups originating
      from lignin. Xylan decay was rapid initially but slowed after 19 months; however,
      oxidative decay of the lignin side chains occurred throughout the 52-month decay
      period. Overall elemental and DRIFT data show that both polysaccharides and
      lignin were decayed during cultivation of the edible white-rot fungus.

PMID- 14658676
TI  - Surface-sensitive molecular information on polymers from UV-resonance Raman
      spectroscopy.
AB  - Ultraviolet resonance Raman spectroscopy (UV-RRS) has been applied to a series of
      samples of poly(ethylene 2,6-naphthalene dicarboxylate) (PEN) and poly(ethylene
      terephthalate) (PET) of varying thickness. The spectra demonstrate that under
      resonance conditions, when absorption is very strong, only a very thin top layer
      of the sample is probed (hundreds of nanometers range). This allows probing
      molecular vibrational spectra of the top layer of the sample, with a surface
      resolution at least an order of magnitude better than in the case of normal non
      resonance Raman spectroscopy and using a microscope.

PMID- 14658677
TI  - Raman spectroscopy-based creatinine measurement in urine samples from a
      multipatient population.
AB  - Spectroscopic methods of urinalysis offer several advantages over chemical
      methods, including less sample contact and higher information content. In
      particular, urine creatinine has been the subject of several spectroscopic
      studies. We report the first use of Raman spectroscopy to measure creatinine
      concentrations in unaltered urine samples from a multipatient population. Using
      near-infrared excitation and a hybrid linear analysis calibration method, a root
      mean squared error of cross-validation (RMSECV) of 4.9 mg/dL was obtained. The
      error in the reference chemical method was 1.1 mg/dL. This result shows that the
      Raman spectroscopy can measure creatinine at clinical levels even in the presence
      of patient-to-patient variations. Because most assays in urine require creatinine
      concentration in order to correct for fluctuations in water content, measurement
      of creatinine is the first step towards more extensive Raman-based urinalysis.

PMID- 14658679
TI  - Self-referencing intensity measurements based on square-wave gated phase
      modulation fluorimetry.
AB  - An adaptation of square-wave gated phase-modulation (GPM) fluorimetry allows for
      self-referenced intensity measurements without the complexity of dual excitation
      or dual emission wavelengths. This AC technique utilizes square-wave excitation,
      gated detection, a reference emitter, and a sensor molecule. The theory and
      experimental data demonstrating the effectiveness and advantages of the adapted
      GPM scheme are presented. One component must have an extremely short lifetime
      relative to the other. Both components are affected identically by changes in
      intensity of the excitation source, but the sensor intensity also depends on the
      concentration of the analyte. The fluctuations of the excitation source and any
      optical transmission changes are eliminated by ratioing the sensor emission to
      the reference emission. As the concentration of the analyte changes, the
      corresponding sensor intensity changes can be quantified through several schemes
      including digitization of the signal and digital integration or AC methods. To
      measure pH, digital methods are used with Na3[Tb(dpa)3] (dpa = 2,6
      pyridinedicarboxylic acid) as the long-lived reference molecule and fluorescein
      as the short-lived sensor molecule. Measurements from the adapted GPM scheme are
      directly compared to conventional ratiometric measurements. Good agreement
      between the data collection methods is demonstrated through the apparent pKa. For
      the adapted GPM measurements, conventional measurements, and a global fit the
      apparent pKa values agree within less than 2%. A key element of the adapted GPM
      method is its insensitivity to fluctuations in the source intensity. For a
      roughly 8-fold change in the excitation intensity, the signal ratio changes by
      less than 3%.

PMID- 14658678
TI  - Photodeposition of silver can result in metal-enhanced fluorescence.
AB  - Chemically deposited silver particles are widely used for surface-enhanced Raman
      scattering (SERS) and more recently for surface-enhanced fluorescence (SEF), also
      known as metal-enhanced fluorescence (MEF). We now show that metallic silver
      deposited by laser illumination results in an approximately 7-fold increased
      intensity of locally bound indocyanine green. The increased intensity is
      accompanied by a decreased lifetime and increased photostability. These results
      demonstrate the possibility of photolithographic preparation of surfaces for
      enhanced fluorescence in microfluidics, medical diagnostics, and other
      applications.

PMID- 14658680
TI  - Diffusional fluorescence quenching of aromatic hydrocarbons.
AB  - The quenching of the fluorescence of five aromatic hydrocarbons by three
      halogenated organics and by molecular oxygen has been measured. Both fluorescence
      intensity and fluorescence lifetime measurements have been employed to validate
      results and interpretation; linear Stern-Volmer analyses are shown to apply
      throughout. The fluorescence quenching rate constant of molecular oxygen for the
      five aromatic hydrocarbons is essentially equivalent to the diffusion rate
      constant independent of the fluorophore excitation energy. The halogenated
      organic-fluorophore rate constants vary by a factor of 965 and are shown to
      correlate roughly with the energy difference between the quencher and fluorophore
      excited electronic states in accord with a standard model of quantum two-level
      mixing. The value of the coupling interaction energy is approximately 2500 cm(
      1).

PMID- 14658681
TI  - Near-infrared spectroscopy for on-line monitoring of lube base oil processes.
AB  - Near-infrared (NIR) spectroscopy has been utilized for monitoring the pour point
      of the lube base oil (LBO) process. Using partial least-squares (PLS) regression,
      necessary spectral features were successfully extracted and correlated to the
      reference pour-point data. In a preliminary laboratory feasibility study, it was
      found that PLS calibration performance was largely governed by the accuracy of
      the reference pour-point analysis. The same NIR spectroscopic methodology was
      moved to monitor the pour point continuously in an on-line manner. At this time,
      the NIR spectrometer was calibrated with the existing on-line pour-point
      analyzer, which was more accurate. In comparison with the on-line pour-point
      analyzer, NIR spectroscopy provided faster and more repeatable analytical data.
      With the help of NIR analysis, LBO process variations during product switch can
      be detected earlier, and necessary process-control strategy can be applied to
      improve the process efficiency.

PMID- 14658682
TI  - Application of partial least-squares regression to near-infrared reflectance
      spectroscopic determination of shive content in flax.
AB  - Shive, the nonfiberous core portion of the stem, in flax fiber after retting is
      related to fiber quality. The objective of this study is to develop a standard
      calibration model for determining shive content in retted flax by using near
      infrared reflectance spectroscopy. Calibration samples were prepared by manually
      mixing pure, ground shive and pure, ground fiber from flax retted by three
      different methods (water, dew, and enzyme retting) to provide a wide range of
      shive content from 0 to 100%. Partial least-squares (PLS) regression was used to
      generate a calibration model, and spectral data were processed using various
      pretreatments such as a multiplicative scatter correction (MSC), normalization,
      derivatives, and Martens' Uncertainty option to improve the calibration model.
      The calibration model developed with a single sample set resulted in a standard
      error of 1.8% with one factor. The best algorithm was produced from first
      derivative processing of the spectral data. MSC was not effective processing for
      this model. However, a big bias was observed when independent sample sets were
      applied to this calibration model to predict shive content in flax fiber. The
      calibration model developed using a combination sample set showed a slightly
      higher standard error and number of factors compared to the model for a single
      sample set, but this model was sufficiently accurate to apply to each sample set.
      The best algorithm for the combination sample set was generated from second
      derivatives followed by MSC processing of spectral data and from Martens'
      Uncertainty option; it resulted in a standard error of 2.3% with 2 factors. The
      value of the digital second derivative centered at 1674 nm for these spectral
      data was highly correlated to shive content of flax and could form the basis for
      a simple, low-cost sensor for the shive or fiber content in retted flax.

PMID- 14658683
TI  - New approach to generalized two-dimensional correlation spectroscopy. II:
      Eigenvalue manipulation transformation (EMT) for noise suppression.
AB  - This paper introduces the concept of eigenvalue manipulating transformation (EMT)
      of a data matrix for noise suppression in two-dimensional (2D) correlation
      spectroscopy. The FT-IR spectra of a polystyrene/methyl ethyl ketone/toluene
      solution mixture during the solvent evaporation process, to which were added a
      substantial amount of artificial noise, have been analyzed. By uniformly raising
      the power of a set of eigenvalues, the major eigenvalues become more prominent.
      As a consequence, minor eigenvectors representing the noise component are no
      longer strongly represented in the reconstructed data. This EMT operation is
      similar to the simple truncation of noise-dominated minor factors practiced in
      standard principal component analysis (PCA), as demonstrated in our preceding
      paper on PCA-2D correlation spectroscopy. The effect of this new EMT scheme is
      more gradual, with attractive flexibility to continuously fine-tune the balance
      between the desired noise reduction effect and the retention of pertinent
      spectral information.

PMID- 14658684
TI  - New approach to generalized two-dimensional correlation spectroscopy. III:
      Eigenvalue manipulation transformation (EMT) for spectral selectivity
      enhancement.
AB  - This paper demonstrates the potential of eigenvalue manipulating transformation
      (EMT) of a data matrix for spectral selectivity enhancement, especially useful in
      2D correlation analysis. The EMT operation aims at the accentuation of select
      features of the information content of the original data matrix. For example, by
      uniformly lowering the power of a set of eigenvalues associated with the original
      data, the smaller eigenvalues become more prominent and the contributions of
      secondary loadings become amplified. As a direct consequence of the minor factor
      accentuation by such EMT operations, 2D correlation spectra gain much stronger
      discriminating power. The selectivity enhancement effect of such manipulation of
      eigenvalues is much more noticeable on the synchronous 2D correlation spectrum.
      This improvement for the spectral selectivity of synchronous 2D correlation
      spectra is potentially very important, as we usually put more emphasis on the
      interpretation of asynchronous 2D spectra in 2D correlation analysis due to
      overlaps of synchronous peaks. Such EMT operations tend to exaggerate the
      information content of minor PCs and reduce that of major PCs. Thus, much more
      subtle difference of spectral behavior for each component is now highlighted.
      Surprisingly, asynchronous 2D correlation spectra are found to be much less
      sensitive to such EMT operations. The result indicates that the distinction of
      different band responses has already been accomplished effectively by the
      original asynchronous 2D correlation analysis.

PMID- 14658685
TI  - Use of broadband, continuous-wave diode lasers in cavity ring-down spectroscopy
      for liquid samples.
AB  - Cavity ring-down spectroscopy (CRDS) is an extremely sensitive absorption
      technique that has been applied primarily to gas samples, which are characterized
      by having narrow absorption features. Recently, CRDS has also been applied to
      liquid samples, which have broad absorption features. The use of small
      inexpensive diode lasers as light sources for liquid samples is demonstrated. The
      low cost coupled with the ease and technical straightforwardness of application
      gives this technique wide appeal.

PMID- 14658686
TI  - Application of mid-infrared spectroscopy: measuring hydrogen peroxide
      concentrations in bleaching baths.
AB  - The presented work applies mid-infrared attenuated total reflection (ATR)
      spectroscopy to the measurment of hydrogen peroxide in aqueous matrices. The
      performance of different ATR crystals mounted in flow cells was investigated in
      the presence of aqueous hydrogen peroxide solutions. Quantitative determination
      has been achieved by evaluation of specific OH stretching and deformation
      vibrations with linear correlation between peak areas or peak heights and
      hydrogen peroxide concentration in the range of 1-10% (weight in water).
      Important aspects such as chemical stability of the waveguide material and
      influences of pH and ionic strength on the performance are discussed. Feasibility
      for the investigation of real world samples is demonstrated by measuring
      industrial bleaching solutions with known concentrations of hydrogen peroxide
      fitting well with calibration graphs established with neat hydrogen peroxide
      solutions. The presented sensor system is capable of determining hydrogen
      peroxide within complex matrices and clearly corroborates the potential of
      providing an in situ measurement concept for on-line hydrogen peroxide detection.

PMID- 14658687
TI  - Safety considerations for sample analysis using a near-infrared (785 nm) Raman
      laser source.
AB  - Raman spectroscopy is often considered a nondestructive analytical technique;
      however, this is not always the case. The 300-mW 785-nm near-infrared (NIR) laser
      source used with many commercially available instruments has sufficient power to
      burn samples. This destructive potential is of special concern if the sample is
      irreplaceable (e.g., fine art, forensic evidence, or for in vivo medical
      diagnostics) or a hazardous energetic material (explosive or pyrophoric samples).
      This study quantifies the heat resulting from illuminating an extensive color
      array with a 785-nm NIR laser and relates these values to the hazards associated
      with Raman analysis. In general, darker colors were found to be more problematic.
      Since visible colors are not ideally correlated with absorptive characteristics
      at 785 nm, predictions based on thermography are not perfect; however, this
      approximation gives a useful method for predicting the thermal response of
      unknown samples to NIR exposure. Additionally, experimental studies evaluated the
      analysis of flammable organic solvents, propellants, military explosives,
      mixtures containing military explosives, shock-sensitive explosives, and
      gunpowders (i.e., smokeless, black, and Pyrodex powders). Safety guidelines for
      analysis are presented.

PMID- 14658688
TI  - ArF laser induced plasma spectroscopy of lead ions in aqueous solutions: plume
      reheating with a second Nd:YAG laser pulse.

PMID- 14658689
TI  - New frontiers for mid-infrared sensors: towards deep sea monitoring with a
      submarine FT-IR sensor system.
AB  - A sub-sea deployable fiber-optic sensor system for the continuous determination
      of a range of environmentally relevant volatile organic compounds in seawater has
      been developed. The prototype of a robust, miniaturized Fourier transform
      infrared (FT-IR) spectrometer for in situ underwater pollution monitoring was
      designed, developed, and built in our research group. The assembled instrument is
      enclosed in a sealed aluminium pressure vessel and is capable of maintenance-free
      operation in an oceanic environment down to depths of at least 300 m. The whole
      system can be incorporated either in a tow frame or a remotely operated vehicle
      (ROV). A suitable fiber-optic sensor head was developed, optimized in terms of
      sensitivity and hydrodynamics, and connected to the underwater FT-IR
      spectrometer. Due to a modular system design, various other sensor head
      configurations could be realized and tested, ensuring facile adaptation of the
      instrument to future tasks. The sensor system was characterized in a series of
      laboratory and simulated field tests. The sensor proved to be capable of
      quantitatively detecting a range of chlorinated hydrocarbons and monocyclic
      aromatic hydrocarbons in seawater down to the low ppb (microg/L) concentration
      range, including mixtures of up to 6 components. It has been demonstrated that
      varying amounts of salinity, turbidity, or humic acids, as well as interfering
      seawater pollutants, such as aliphatic hydrocarbons or phenols, do not
      significantly influence the sensor characteristics. In addition, the sensor
      exhibits sufficient long-time stability and a low susceptibility to sensor
      fouling.

PMID- 14658690
TI  - Development and optimization of a mid-infrared hollow waveguide gas sensor
      combined with a supported capillary membrane sampler.
AB  - A gas sensor for application in water analysis was developed by combination of a
      mid-infrared (MIR) hollow waveguide with a Fourier transform infrared (FT-IR)
      spectrometer and coupling of the hollow waveguide gas sensor module to a
      supported capillary membrane sampler (SCMS) for continuous liquid-gas extraction.
      Different hollow waveguides have been characterized in this study for developing
      an optimized optical configuration. Analysis of industrially relevant compounds
      has been performed, investigating chlorinated hydrocarbons (CHCs), such as
      dichloromethane and chloroform, representing highly volatile analytes, and 1,4
      dioxane as an example of target compounds with low volatility. The suitability of
      this spectroscopic IR sensing system for industrial applications is demonstrated
      under simulated real-world conditions with limits of detection in the ppb (v/v)
      and ppm (v/v) concentration range for CHCs and 1,4-dioxane, respectively.

PMID- 14658691
TI  - In situ sensing of volatile organic compounds in groundwater: first field tests
      of a mid-infrared fiber-optic sensing system.
AB  - A prototype mid-infrared sensor system for the determination of volatile organic
      pollutants in groundwater was developed and tested under real-world conditions.
      The sensor comprises a portable Fourier transform infrared spectrometer, coupled
      to the sensor head via mid-infrared transparent silver halide fiber-optic cables.
      A 10 cm unclad middle section of the 6-m-long fiber is coated with ethylene
      propylene copolymer in order to enrich the analytes within the penetration depth
      of the evanescent field protruding from the fiber sensor head. A mixture of
      tetrachloroethylene, dichlorobenzene, diethyl phthalate, and xylene isomers at
      concentrations in the low ppm region was investigated qualitatively and
      quantitatively in an artificial aquifer system filled with Munich gravel. This
      simulated real-world site at a pilot scale enables in situ studies of the sensor
      response and spreading of the pollutants injected into the system with controlled
      groundwater flow. The sensor head was immersed into a monitoring well of the
      aquifer system at a distance of 1 m downstream of the sample inlet and at a depth
      of 30 cm. Within one hour, the analytes were clearly identified in the
      fingerprint region of the IR spectrum (1300 to 700 cm(-1)). The results have been
      validated by head-space gas chromatography, using samples collected during the
      field measurement. Five out of six analytes could be discriminated
      simultaneously; for two of the analytes the quantitative results are in agreement
      with the reference analysis.

PMID- 14658692
TI  - Error analysis for estimation of trace vapor concentration pathlength in stack
      plumes.
AB  - Near-infrared hyperspectral imaging is finding utility in remote sensing
      applications such as detection and quantification of chemical vapor effluents in
      stack plumes. Optimizing the sensing system or quantification algorithms is
      difficult because reference images are rarely well characterized. The present
      work uses a radiance model for a down-looking scene and a detailed noise model
      for dispersive and Fourier transform spectrometers to generate well-characterized
      synthetic data. These data were used with a classical least-squares-based
      estimator in an error analysis to obtain estimates of different sources of
      concentration-pathlength quantification error in the remote sensing problem.
      Contributions to the overall quantification error were the sum of individual
      error terms related to estimating the background, atmospheric corrections, plume
      temperature, and instrument signal-to-noise ratio. It was found that the
      quantification error depended strongly on errors in the background estimate and
      second-most on instrument signal-to-noise ratio. Decreases in net analyte signal
      (e.g., due to low analyte absorbance or increasing the number of analytes in the
      plume) led to increases in the quantification error as expected. These
      observations have implications on instrument design and strategies for
      quantification. The outlined approach could be used to estimate detection limits
      or perform variable selection for given sensing problems.

PMID- 14658693
TI  - Interaction between a capacitor electrolyte and gamma-aluminum oxide studied by
      Fourier transform infrared spectroscopy.
AB  - The interaction between y-aluminum oxide and an ethylene glycol (EG) based
      capacitor electrolyte was investigated by Fourier transform infrared (FT-IR)
      spectroscopy. It was found that only a few ingredients of the electrolyte react
      with the oxide (azelaic acid, poly(1-vinyl-2-pyrrolidone) (PVP), and phosphoric
      acid); the others act as pH or conductivity buffers (boric acid, ammonia, and
      water). The adsorption of azelaic acid and PVP from the electrolyte was studied
      as a function of temperature, pH, and time, and the result was compared to the
      adsorption from model solutions of simpler composition. The influence of other
      components such as phosphoric acid both in the electrolyte and on the aluminum
      oxide was also investigated, as was the presence of water. At low pH and high
      temperature (T > or = 105 degrees C) the acid formed an ester with EG and this
      product adsorbed on the oxide surface. The PVP was attached to the adsorbed
      azelaic acid by hydrophobic interaction, which is pH independent. Ester formation
      was found to be catalyzed by other electrolyte ingredients like boric acid. At
      high pH, surface adsorption of azelaic acid occurs through a deprotonated
      species, which is mainly coordinated through outer-sphere complexation. At high
      temperature or after a long equilibration time, the surface of the alumina
      changed, resulting in less adsorption of the organic substances, independent of
      pH. This change is due to a selective adsorption of phosphate species from the
      electrolyte, which block active surface sites.

PMID- 14658694
TI  - Molecular composition and orientation of interstitial versus surface silicon
      oxides for Si(111)/SiO2 and Si(100)/SiO2 interfaces using FT-IR and X-ray
      photoelectron spectroscopies.
AB  - This work represents a characterization study of silicon oxide on Si(111) and
      Si(100) surfaces intended for use as substrates in organic light-emitting diodes
      (OLEDs) on chip devices. Samples have been prepared using either native oxide
      formation or thermal oxidation, and they have also been treated for activation of
      hydroxyl groups on their surface. Both Fourier transform infrared (FT-IR) and X
      ray photoelectron spectroscopy (XPS) have been used in order to understand the
      molecular orientation as well as the chemical composition of the various oxide
      types formed during these different oxidation processes. These spectroscopic
      studies reveal the formation of two different types of oxides on these
      substrates. The first type is a thin oxide layer on the surface, whereas the
      second type, called interstitial, is found deeper in the substrate. Specifically,
      it was found that the Si(100) substrate forms a randomly oriented interstitial
      oxide, whereas the presence of a lower quantity but more oriented interstitial
      oxide was found for the Si(111) substrate. In addition, we report for the first
      time the position of the impurity oxygen for Si(111) substrates at 1122 cm(-1).
      Finally, in both Si(100) and Si(111) substrates, the thin (<15 A) silicon oxide
      layers are oriented and appear to contain silicon atoms of similar oxidation
      states. In contrast, both the thicker surface film (100 A) as well as the
      interstitial oxide produced by the thermal oxidation procedure show random
      orientation and relative uniformity. Overall these orientation studies clearly
      show that the formation process of surface oxides in different substrates clearly
      creates species that are oriented differently with respect to the surface.

PMID- 14658695
TI  - FT-IR microspectroscopic study of shot formation in melt-blown webs.
AB  - We used Fourier transform infrared (FT-IR) microspectroscopy to investigate the
      chemical nature of fibers and defects called "shot" in melt-blown webs. Spectral
      differences were observed and evaluated in light of known thermal and oxidative
      degradation reactions for conditions comparable to those we used for melt
      blowing. Three different isotactic polypropylene polymers were evaluated in terms
      of the amount of shot produced and the amount of oxidative degradation exhibited
      by fibers and shot particles from each polymer. Little oxidative degradation was
      observed in fibers and the amount of degradation in fibers varied little for the
      three polymers we evaluated. Substantially more degradation was observed in shot
      particles, and the amount of degradation varied among the three polymers.
      Compared to polymer bound for fibers, we concluded that high temperature and
      mechanical shear in the extruder may introduce more chain scission in polymer
      bound for shot particles. Autoxidation reactions may occur after melt exits the
      die, and our data indicated that more oxidative degradation occurred in polymer
      that became shot particles than polymer that became fibers. The most favorable
      site for oxidation seemed to be tertiary rather than methylene hydrogen. Overall,
      the thermal history of polymer that becomes shot particles may be significantly
      different than the thermal history of polymer that becomes fibers, and this
      difference may have influenced shot formation.

PMID- 14658696
TI  - Effect on the partial least-squares prediction of yarn properties combining raman
      and infrared measurements and applying wavelength selection.
AB  - The combination of Raman and infrared spectroscopy on the one hand and wavelength
      selection on the other hand is used to improve the partial least-squares (PLS)
      prediction of seven selected yarn properties. These properties are important for
      on-line quality control during production. From 71 yarn samples, the Raman and
      infrared spectra are measured and reference methods are used to determine the
      selected properties. Making separate PLS models for all yarn properties using the
      Raman and infrared spectra, prior to wavelength selection, reveals that Raman
      spectroscopy outperforms infrared spectroscopy. If wavelength selection is
      applied, the PLS prediction error decreases and the correlation coefficient
      increases for all properties. However, a substantial wavelength selection effect
      is present for the infrared spectra compared to the Raman spectra. For the
      infrared spectra, wavelength selection results in PLS prediction errors
      comparable with the prediction performance of the Raman spectra prior to
      wavelength selection. Concatenating the Raman and infrared spectra does not
      enhance the PLS prediction performance, not even after wavelength selection. It
      is concluded that an infrared spectrometer, combined with a wavelength selection
      procedure, can be used if no (suitable) Raman instrument is available.

PMID- 14658697
TI  - Surface-enhanced resonance raman scattering: single-molecule detection in a
      Langmuir-Blodgett monolayer.
AB  - Surface-enhanced resonance Raman scattering (SERRS) is used for single-molecule
      detection from spatially resolved 1-microm2 sections of a Langmuir-Blodgett (LB)
      monolayer deposited onto a Ag film. The target molecule, bis (benzimidazo)
      thioperylene (BZP), is dispersed in an arachidic acid monomolecular layer
      containing one BZP molecule per microm2, which is also the probing area of the
      Raman microscope. For concentrated samples (attomole quantities in the field of
      view), average SERRS, surface-enhanced fluorescence (SEF), and Raman imaging,
      including line mapping and global images at different temperatures, were
      recorded. Single-molecule SERRS spectra, obtained using an LB monolayer, present
      changes in bandwidth and relative intensities, highlighting the properties of
      single-molecule SERRS that are lost in average SERRS measurements of mixed LB
      monolayers obtained at the same temperatures. Also, the dilute system phenomenon
      of blinking is discussed with regard to results obtained from LB monolayers. The
      dilution process used in the single-molecule LB SERRS work is independently
      supported by fluorescence results obtained from very dilute solutions with
      monomer concentrations down to 10(-12) M.

PMID- 14658698
TI  - Silver clusters onto nanosized colloidal silica as novel surface-enhanced Raman
      scattering active substrates.
AB  - A new method is proposed for obtaining surface-enhanced Raman scattering (SERS)
      active substrates by photochemical reduction of silver nitrate onto colloidal
      silica. Transmission electron microscopy (TEM) and UV-visible absorption
      spectroscopy are employed to investigate the nanoscale structure of the
      materials. High quality SERS spectra are obtained from different organic ligands
      to check the efficiency of these substrates. A marked stability of the colloidal
      suspension is ensured by the scarce tendency of the Ag-doped silica particles to
      aggregate by either aging or adsorption of ligand.

PMID- 14658699
TI  - Monitoring the temperature of dilute aqueous solutions using near-infrared water
      absorption.
AB  - An alternative spectroscopic approach for monitoring the temperature of aqueous
      solutions is presented. The method is based upon the temperature-induced spectral
      changes undergone by the second overtone (around 960 nm) of the near-infrared
      (NIR) water absorption band. Single and multilinear regression analysis are
      tested in order to evaluate the predictive ability of temperature. A linear
      dependence is found when measurements are performed at a single wavelength, but a
      lower prediction error is obtained when multilinear models are applied. No matrix
      effects produced by moderately concentrated common dissolved ions are found in a
      broad range of pH. A signal-to-noise ratio allows a precision of 0.5 degrees C
      for temperature monitoring. A prediction error of 0.77 degrees C (single linear
      regression) and 0.25 degrees C (multilinear approach) are achieved in a range
      from 15 to 90 degrees C. Advantages in terms of instrumentation and data analysis
      required are discussed.

PMID- 14658700
TI  - Near-infrared spectroscopic monitoring of the diffusion process of deuterium
      labeled molecules in wood. Part I: softwood.
AB  - The diffusion process of several molecules (D2O, n-butanol (OD) and t-butanol
      (OD)) in softwood (Sitka spruce) was investigated by means of a deuterium
      exchange method and Fourier transform near-infrared (FT-NIR) polarization
      spectroscopy. The location of OH groups in different states of order of cellulose
      in wood was clarified by analyzing the FT-NIR transmission spectra ranging from
      7200 to 6000 cm(-1). Four absorption bands were assigned to 2 x v(OH) absorptions
      of the amorphous regions, OH groups in semi-crystalline regions, and two types of
      intramolecular hydrogen-bonded OH groups in the crystalline regions,
      respectively. The saturation level of accessibility was very different for these
      absorption bands (i.e., 70-80, 60, and 40-50% for the amorphous, semi
      crystalline, and crystalline regions, respectively). However, the saturation
      accessibilities for each absorption band varied little with molecular structure
      and geometry of the diffusants. The diffusion rate of D2O was much faster than
      that of n-butanol (OD) and t-butanol (OD) for all states of orders. The size
      effect of the butanols led to slight differences in the diffusive transport in
      the crystalline regions.

PMID- 14658701
TI  - Near-infrared spectroscopic monitoring of the diffusion process of deuterium
      labeled molecules in wood. Part II: hardwood.
AB  - Fourier transform near-infrared (FT-NIR) transmission spectroscopy was applied to
      monitor the diffusion process of deuterium-labeled molecules in hardwood (Beech).
      The results are compared with previous data obtained on softwood (Sitka spruce)
      in order to consistently understand the state of order in cellulose of wood. The
      saturation accessibility and diffusion rate varied characteristically with the OH
      groups in different states of order in the wood substance, the diffusants, and
      the wood species, respectively. The variation of saturation accessibility should
      be associated with the fundamental difference of the fine structure such as the
      microfibrils in the wood substance. The effect of the anatomical cellular
      structure on the accessibility was reflected in the variation of the diffusion
      rate with the wood species. The size effect of the diffusants also played an
      important role for the diffusion process in wood. Since the volumetric percentage
      of wood fibers and wood rays is relatively similar, the dichroic effects due to
      the anisotropy of the cellulose chains were apparently diminished. Finally, we
      proposed a new interpretation of the fine structure of the microfibrils in the
      cell wall by comparing a series of results from hardwood and softwood. Each
      elementary fibril in the hardwood has a more homogeneous arrangement in the
      microfibrils compared to that in the softwood.

PMID- 14658702
TI  - Fluorescence microspectroscopy technique for the study of intracellular
      protoporphyrin IX dynamics.
AB  - We describe a technique designed to monitor the fluorescence dynamics of
      photosensitizers used in photodynamic therapy (PDT) at micrometer-scale locations
      within individual formalin-fixed cells. The accumulation of protoporphyrin IX
      (PpIX) within keratinocytes and fibroblasts. following incubation with 5
      aminolaevulinic acid (ALA), is shown to be dependent upon both incubation time
      and cell proliferation status. Also, the process of photobleaching within these
      cells is demonstrated via the depletion in PpIX fluorescence emission during
      exposure to 532 nm light. All spectra show a progressive reduction of the 634 nm
      PpIX peak, following a bi-exponential decay that is consistent with a singlet
      oxygen mediated process. The rate of photobleaching, when plotted as a function
      of light dose, increases with reduced incident laser power. The generation of the
      hydroxyaldehyde-chlorin photoproduct (photoprotoporphyrin), as monitored by the
      increase in fluorescence emission centered on 672 nm, is also greatest when the
      lowest laser power is applied. When light is delivered in two fractions, PpIX
      fluorescence recovers during the dark period and there is an increase in
      bleaching rate at the onset of the second exposure. These results are
      qualitatively consistent with measurements performed in vivo, which demonstrate
      that the photodynamic dose is dependent upon fluence rate and oxygen status.

PMID- 14658703
TI  - Two-dimensional imaging biosensor for the monitoring of lactate released from
      brain slices.
AB  - Real-time monitoring of lactate release from brain slices has been studied with
      an optical two-dimensional (2D) imaging biosensor. The 2D biosensor is prepared
      by direct immobilization of lactate dehydrogenase (LDH) molecules onto a flat
      silica glass surface through a covalent binding mechanism. The biosensor is able
      to spatially differentiate lactate concentration variations with conventional
      optical microscopic spatial resolution. This biosensor has the capability to
      effectively detect lactate down to a concentration of 100 nM. The 2D biosensor
      responds uniformly with 2.5% RSD from pixel to pixel. With a 100 ms response
      time, this 2D biosensor has the capability of monitoring simultaneously many
      cells in one image. We have studied the impact of KCI on lactate release from
      brain slices. Clear differences have been observed in lactate release for
      different regions of the tissue. The real-time determination of the newly
      released lactate from the mouse brain slices clearly demonstrates the feasibility
      of monitoring lactate release from living specimens. The 2D biosensor will enable
      us to study cellular communications and possibly other biological processes that
      require simultaneous temporal and spatial resolution.

PMID- 14658704
TI  - Fluorescence line narrowing spectroscopy of polycyclic aromatic hydrocarbons on
      solid-liquid extraction membranes.
AB  - The potential of solid-liquid extraction fluorescence line narrowing spectroscopy
      is evaluated for screening polycyclic aromatic hydrocarbons in aqueous samples.
      Octadecyl silica membranes are used with the dual purpose of sample
      preconcentration and solid substrate for spectroscopic measurements. 4.2 K
      fluorescence line narrowed spectra are directly recorded from the membrane with
      the aid of a fiber-optic probe. The experimental procedure is free from organic
      solvents and takes less than 5 min per sample. With 10 mL of water sample, the
      limits of detection are at the parts-per-billion level. Qualitative analysis is
      based on wavelength time matrices, which provide a unique format for compound
      identification based on spectral and lifetime data. The selectivity of this
      approach is demonstrated with the unambiguous determination of naphthalene in a
      heavily contaminated water sample.

PMID- 14658705
TI  - Development and application of acousto-optic background correction for
      inductively coupled plasma atomic emission spectrometry.
AB  - In two configurations, a solid-state acousto-optic (AO) deflector or modulator is
      mounted in a 0.5 m monochromator for background correction with inductively
      coupled plasma atomic emission spectrometry (ICP-AES). A fused silica acousto
      optic modulator (AOM) is used in the ultraviolet (UV) spectral region
      applications while a glass AO deflector (AOD) is used for the visible (VIS)
      region. The system provides rapid sequential observation of adjacent on- and off
      line wavelengths for background correction. Seventeen elements are examined using
      pneumatic nebulization (PN) and electrothermal vaporization (ETV) sample
      introduction. Calibration plots were obtained with each sample introduction
      technique. Potable water and vitamin tablets were analyzed. Flame atomic
      absorption (FAA) was used to verify the accuracy of the AO background correction
      system.

PMID- 14658706
TI  - Inductively coupled plasma atomic emission spectrometry: an efficient tool for
      precise determination of Mg/Ca and Sr/Ca ratios in biocarbonates.
AB  - A method is developed to precisely determine Mg/Ca and Sr/Ca ratios in
      biocarbonates by inductively coupled plasma atomic emission spectrometry (ICP
      AES). This method precision (RSD%) is 0.52% for Mg/Ca and 0.28% for Sr/Ca,
      respectively. The precision suggests that ICP-AES is satisfactory for supplying
      good quality Mg/Ca and Sr/Ca data of biocarbonates for paleo-reconstruction. This
      ICP-AES technique was applied to 51 continuous coral subsamples, and the results
      show annually periodical variations in coral Mg/Ca and Sr/Ca ratios, which are
      consistent with previous findings.

PMID- 14658707
TI  - Temporal and spatial evolution of a laser-induced plasma from a steel target.
AB  - The space and time evolution of a laser-induced plasma from a steel target has
      been studied using optical time-of-flight and shadowgraphic techniques. The
      results, obtained for two distinct laser energy regimes, allow us to individuate
      two different regions in the plume, one characterized by air and continuum
      emissions produced by the shock wave ionization and the other characterized by
      emissions from ablated material. Moreover, it was shown that a sufficiently high
      laser fluence and short delay time of acquisition are needed to avoid
      inhomogeneous effects in the plasma, as required in analytical applications such
      as laser-induced breakdown spectroscopy.

PMID- 14658708
TI  - In-line fiber-optic light filter.

PMID- 14658709
TI  - Single-reflection attenuated total reflection of organic monolayers on silicon.

PMID- 14658710
TI  - D-dimer as a new test for the diagnosis of DIC and thromboembolic disease.

PMID- 14658711
TI  - The basic biology of malignant melanoma: molecular mechanisms of disease
      progression and comparative aspects.
AB  - Malignant melanoma (MM) is a life-threatening disease characterized by a highly
      aggressive biologic behavior in both humans and dogs. Despite improvements in
      diagnosis and patient care, most deaths from MM are due to metastases that are
      resistant to conventional treatment modalities. To ultimately reduce the
      mortality associated with metastatic disease, it is necessary to better define
      the fundamental molecular mechanisms of malignant tumor progression. The
      progression of disease is a consequence of the complex interactions between
      malignantly transformed cells and host factors. Characterization of the stages of
      tumor progression and the changes occurring in highly malignant cells is
      important for the development of effective treatment regimens. The dys-regulated
      molecular mechanisms of transformed melanocytes are presently being
      characterized. In this review, we summarize the current understanding of the
      molecular phases in the progression of MM, which include genetic instability,
      dysregulated proliferation of melanocytes, increased invasion and metastasis, and
      angiogenesis.

PMID- 14658712
TI  - Dynamic computed tomography of the pituitary gland in dogs with pituitary
      dependent hyperadrenocorticism.
AB  - Dynamic computed tomography (CT) of the pituitary gland was performed in 55 dogs
      with pituitary-dependent hyperadrenocorticism (PDH) that underwent
      transsphenoidal hypophysectomy. On routine contrast-enhanced CT images,
      microadenomas of the pituitary gland often are indistinguishable from nontumorous
      pituitary tissue because of isoattenuation. Dynamic CT may allow visualization of
      these adenomas. The changes in the contrast-enhancement pattern of the pituitary
      during dynamic CT in 55 dogs with PDH were correlated with surgical and
      histopathologic findings. In 36 dogs, dynamic CT identified distinct contrast
      enhancement of the neurohypophysis (pituitary flush). In 24 dogs, this pituitary
      flush was displaced, which indicated the presence of an adenoma. This observation
      was confirmed surgically and histopathologically in 18 of the 24 dogs. In 19
      dogs, there was a diffusely abnormal contrast-enhancement pattern. CT findings
      agreed with surgical findings in 13 of these dogs and with histopathologic
      findings in all 19 dogs. It is concluded that a dynamic series of scans should be
      included in the CT protocol of the pituitary gland in dogs with PDH because it
      allows for identification of an adenoma or a diffusely abnormal pituitary gland.

PMID- 14658713
TI  - Comparison of different tests to diagnose feline infectious peritonitis.
AB  - Clinical data from 488 cats (1979-2000) with histopathologically confirmed feline
      infectious peritonitis (FIP) and 620 comparable controls were evaluated
      retrospectively to assess the value of several diagnostic tests frequently used
      in the evaluation of cats with suspected FIP. Diagnostic utility of serum albumin
      to globulin ratio for the diagnosis of FIP was greater than of the utility of
      serum total protein and gamma-globulin concentrations. Diagnostic utility of
      these variables was higher when performed on effusion. On effusion, positive and
      negative predictive values of Rivalta's test, a test that distinguishes between
      exudates and transudates (0.86 and 0.97), anti-coronavirus antibody detection
      (0.90 and 0.79), and immunofluorescence staining of coronavirus antigen in
      macrophages (1.00 and 0.57) were investigated. The positive and negative
      predictive values of presence of anti-coronavirus antibodies were 0.44 and 0.90,
      respectively, antibody concentrations (1:1,600) were 0.94 and 0.88. presence of
      immune complexes measured by a competitive enzyme-linked immunosorbent assay were
      0.67 and 0.84, and detection of viral RNA by serum reverse-transcriptase
      polymerase chain reaction (RT-PCR) were 0.90 and 0.47. Effusion RT-PCR was
      performed in 6 cats; it was positive in all 5 cats with FIP and negative in the
      cat with another disease. Diagnostic assays on the fluid in cats with body
      effusion had good predictive values. Definitive diagnosis of FIP on the basis of
      measurement of various variables in serum was not possible. Serum tests can only
      be used to facilitate the decision for more invasive diagnostic methods.

PMID- 14658714
TI  - Effect of early enteral nutrition on intestinal permeability, intestinal protein
      loss, and outcome in dogs with severe parvoviral enteritis.
AB  - A randomized, controlled clinical trial investigated the effect of early enteral
      nutrition (EN) on intestinal permeability, intestinal protein loss, and outcome
      in parvoviral enteritis. Dogs were randomized into 2 groups: 15 dogs received no
      food until vomiting had ceased for 12 hours (mean 50 hours after admission; NPO
      group), and 15 dogs received early EN by nasoesophageal tube from 12 hours after
      admission (EEN group). All other treatments were identical. Intestinal
      permeability was assessed by 6-hour urinary lactulose (L) and rhamnose (R)
      recoveries (%L, %R) and L/R recovery ratios. Intestinal protein loss was
      quantified by fecal alpha1-proteinase inhibitor concentrations (alpha1-PI).
      Median time to normalization of demeanor, appetite, vomiting, and diarrhea was 1
      day shorter for the EEN group for each variable. Body weight increased
      insignificantly from admission in the NPO group (day 3: 2.5 +/- 2.8%; day 6: 4.3
      +/- 2.3%; mean +/- SE), whereas the EEN group exhibited significant weight gain
      (day 3: 8.1 +/- 2.7%; day 6: 9.7 +/- 2.1%). Mean urinary %L was increased, %R
      reduced, and L/R recovery ratios increased compared to reference values
      throughout the study for both groups. Percent lactulose recovery decreased in the
      EEN group (admission: 22.6 +/- 8.0%; day 6: 17.9 +/- 2.3%) and increased in the
      NPO group (admission: 11.0 +/- 2.6%; day 6: 22.5 +/- 4.6%, P = .035). Fecal
      alpha1-PI was above reference values in both groups and declined progressively.
      No significant differences occurred for %R, L/R ratios, or alpha1-PI between
      groups. Thirteen NPO dogs and all EEN dogs survived (P = .48). The EEN group
      showed earlier clinical improvement and significant weight gain. The
      significantly decreased %L in the EEN versus NPO group might reflect improved gut
      barrier function, which could limit bacterial or endotoxin translocation.

PMID- 14658716
TI  - Initial and long-term efficacy of a lipid emulsion of amphotericin B
      desoxycholate in the management of canine leishmaniasis.
AB  - Sixteen dogs in which canine leishmaniasis (CL) was diagnosed by positive
      identification of Leishmania amastigotes in bone marrow samples were treated with
      a mixture of amphotericin B (AmB) desoxycholate in soybean oil. To prevent the
      toxicity of AmB, dogs were pretreated with saline (50 mL/kg) and mannitol (2
      g/kg). Dogs were treated twice weekly with an increasing dosage of amphotericin
      (0.8-2.5 mg/kg) for between 8 and 10 sessions. Transient adverse effects
      (anorexia, vomiting, or both) appeared in 81% of the dogs during therapy. At the
      end of the course, all dogs were clinically cured, with no parasites observed in
      bone marrow smears. Six of the 16 dogs (38%) were positive by polymerase chain
      reaction (PCR) in bone marrow samples at some stage of their follow-up, but only
      2 were positive at the first test after treatment, which was performed within 5
      months after the end of the therapy. The other 4 dogs were initially negative and
      became PCR-positive at subsequent examinations. Three of these 6 dogs also
      experienced a clinical relapse. Four dogs had at least 3 consecutive negative PCR
      tests during a minimum period of 18 months and were clinically cured. The results
      of the present study indicate that despite having a high initial effectiveness in
      the treatment of CL, relapses can occur with the described protocol. Also, a
      single negative PCR result in a recently treated dog cannot be interpreted as a
      complete cure.

PMID- 14658715
TI  - Prevalence of Chlamydophila felis and feline herpesvirus 1 in cats with
      conjunctivitis in northern Italy.
AB  - The prevalence of Chlamydophila felis and feline herpesvirus 1 (FHV-1) infection
      in cats with conjunctivitis in northern Italy was investigated by conventional
      polymerase chain reaction (PCR) testing. In cats with conjunctivitis, C felis and
      FHV-1 were detected in 14 of 70 (20%) and in 23 of 70 (33%) animals,
      respectively. None of the 35 control cats were positive for C felis, whereas 7
      (20%) of these cats were positive for FHV-1. Mixed infections were present in 5
      of 70 cats (7%). Cats positive for C felis were significantly younger than
      control animals (P = .02), whereas no significant age differences were observed
      between FHV-1-positive cats and control cats (P = .41) or between FHV-1-positive
      animals and C felis-positive animals (P = .16). Cats sampled during acute-phase
      conjunctivitis were also investigated for the presence of C felis by conjunctival
      scrapings. In this acute phase, substantial agreement was found when comparing
      the results of the 2 methods (K = .80). The association between PCR results and
      conjunctivitis was evaluated for the 2 pathogens. The presence of C felis was
      significantly associated with conjunctivitis (P = .004), whereas the detection of
      FHV-1 did not significantly correlate with the clinical sign (P = .25),
      suggesting that, by itself. PCR is not suitable for the diagnosis of FHV-1
      related conjunctivitis.

PMID- 14658717
TI  - Outbreak of Clostridium difficile-associated disease in a small animal veterinary
      teaching hospital.
AB  - An apparent outbreak of enteric disease occurred in dogs and cats at a veterinary
      teaching hospital. Clostridium difficile Toxin A or B or both were identified in
      1 or more fecal samples from 48 of 93 (52%) dogs over a 5-month period, 30 of
      which were identified in the 1st 26 days, after which strict infection control
      measures, including closure to elective cases, were implemented. Affected animals
      included in-patients, out-patients that were housed temporarily in the wards, and
      resident blood donor dogs. Infection control measures, including partial
      depopulation, isolation, hospital and yard cleaning, and barrier precautions,
      were instituted, after which, the incidence of nosocomial diarrhea decreased from
      19 cases per 1,000 admissions to 2.5 cases per 1,000 admissions (P < 0.001).

PMID- 14658718
TI  - Changes in proportion of canine urinary calculi composed of calcium oxalate or
      struvite in specimens analyzed from 1981 through 2001.
AB  - The objective of this report was to characterize 20-year changes in proportion of
      calcium oxalate (CaOx) calculi and struvite calculi in dogs, and associations
      with breed, age, and sex. In this retrospective study, results of analysis of
      urinary calculi from dogs were reviewed for specimens received between July 1,
      1981, and December 31, 2001. Breed, sex, age, year of submission of the specimen,
      and mineral type(s) were analyzed statistically. CaOx or Struvite or both were
      contained in 18,966 of 20,884 (91%) specimens. For both sexes, a 20-year
      statistically significant increase was observed in the proportion of calculus
      specimens that contained CaOx. The increase in this proportion was greater in
      females (1% to 31%) than in males (18% to 82%). From 1998 to 2001, when
      proportions may have plateaued, the odds of specimens containing CaOx were
      markedly higher in 18 breeds, markedly lower in 5 breeds, and not significantly
      different in 13 breeds compared with crossbreds. For both sexes, a 20-year
      statistically significant decrease was observed in the proportion of calculus
      specimens that contained struvite. This decrease in proportion was greater for
      males (79-16%) than for females (97-68%). From 1998 to 2001, when proportions
      plateaued, the odds of calculi containing struvite were markedly lower in 20
      breeds, markedly higher in 1 breed, and not significantly different in 15 breeds
      when compared with crossbreds. Breed, age, and sex were associated statistically
      with CaOx or struvite urolithiasis. In conclusion, there appears to have been a
      long-term increase in the proportion of specimens of canine urinary calculi that
      contain CaOx as well as a long-term decrease in the proportion of specimens of
      calculi that contain struvite for both male and female dogs. The rate of change
      appeared to begin leveling off in the period 1998 to 2001. The recent proportion
      of dogs with either CaOx- or struvite-associated urolithiasis may depend on
      breed, age, and sex, and on interactions among these 3 factors.

PMID- 14658719
TI  - Increased pulmonary transit times in asymptomatic dogs with mitral regurgitation.
AB  - Pulmonary transit time (PTT) normalized to heart rate (nPTT) is a measure of the
      pulmonary blood volume (PBV) to stroke volume ratio (PBV/SV). It is an index of
      cardiac performance. To determine the effect of compensated mitral regurgitation
      (CMR) and decompensated mitral regurgitation (DMR) caused by valvular
      endocardiosis on the index nPTT, we measured nPTT by first-pass radionuclide
      angiocardiography and ECG in 13 normal dogs, 18 dogs with CMR, and 13 dogs with
      DMR. PTT was measured as time between onset of appearance of activity at the
      pulmonary trunk and the left atrium. In the normal dogs, the relationship between
      PTT and mean R-R interval (mRR) was PTT = 4.08 x mRR + 0.15 (R2 = 0.71). Normal
      nPTT was 4.4 +/- 0.6 (SD) (range. 3.6-5.3). in CMR, 6.3 +/- 1.6 (SD) (range, 4.0
      9.7). and in DMR, 11.9 +/- 3.4 (SD) (range, 8.0-18.8). The differences among all
      groups were significant. Heart rates were 110 +/- 22 bpm in normal dogs, 111 +/-
      20 in dogs with CMR, and 144 +/- 18 in dogs with DMR (P < .001 for difference
      between DMR group and normal and CMR groups). Increased nPTT in CMR indicates
      preclinical heart pump dysfunction. Heart rate-normalized pulmonary transit times
      may be a useful index of heart function in mitral regurgitation.

PMID- 14658720
TI  - The utility of plasma D-dimer to identify thromboembolic disease in dogs.
AB  - This prospective study was designed to investigate D-dimer concentrations in
      clinically healthy dogs, clinically ill dogs without thromboembolic disease (TE),
      and dogs with TE. The goals of this study were to determine whether the
      coagulation cascade is activated in nonembolic metabolic and inflammatory
      conditions and whether differentiation from TE is possible. Group 1 consisted of
      30 clinically healthy dogs presented for routine care. Group 2 consisted of 67
      clinically ill dogs without TE. This group was subdivided into the following
      categories: postoperative surgical procedures, congestive heart failure, renal
      failure, hepatic disease, and neoplastic disease. Group 3 consisted of 20 dogs
      diagnosed with TE. A CBC and a measurement of prothrombin time (PT), activated
      partial thromboplastin time (PTT), fibrinogen degradation product (FDP)
      concentration, and plasma D-dimer concentration was performed on dogs in all
      groups. D-dimer concentrations were highest in dogs with TE; next highest was the
      hepatic disease group. Only these 2 groups had median D-dimer concentrations
      markedly different from clinically healthy dogs. The frequency of platelet
      abnormalities was markedly greater for the TE and neoplastic disease groups. The
      sensitivity of D-dimer concentrations >500 ng/mL for predicting TE was 100%;
      however, the specificity of D-dimer for TE at that concentration was 70%. The
      specificity of D-dimer concentrations >1,000 ng/mL to predict TE was 94%
      (sensitivity, 80%), and the specificity of D-dimer concentrations >2,000 ng/mL
      was 98.5% (sensitivity, 36%). FDPs were not high in any TE patient; thus, they
      may be an insensitive indicator of thromboembolism, with or without overt
      disseminated intravascular coagulation (DIC).

PMID- 14658721
TI  - Effects of age and dietary beta-carotene on immunological variables in dogs.
AB  - beta-Carotene is a naturally occurring carotenoid reported to have health
      promoting effects in several species. Advancing age is known to have a negative
      impact on various immune variables in several species. This study was conducted
      in order to assess the effect of age on immune response in dogs and to determine
      whether beta-carotene is able to reverse this age-associated decline. To test
      this hypothesis, young and old dogs (n = 36) were fed either a control diet or
      experimental diets containing supplemental beta-carotene for 2-month periods. Age
      significantly (P < .05) lowered CD4+ T cell populations (47.2% versus 33.7%;
      young-control versus old-control, respectively) and beta-carotene restored
      percent distributions in old dogs to nonsignificance versus younger controls
      (41.0%). T cell proliferation was lower in old dogs (30,254 +/- 2,248 versus
      14,811 +/- 2,497 cCPM; young-control versus old-control, respectively; P < .05),
      and beta-carotene supplementation significantly improved responses in this age
      group (21,329 +/- 2,275 cCPM). Although B cell proliferation was depressed with
      age (17,967 +/- 1,384 versus 7,535 +/- 1,469 cCPM; young-control versus old
      control, respectively; P < .05), beta-carotene supplementation improved B cell
      proliferation in young dogs (23,500 +/- 1,339 cCPM). Old dogs displayed lower
      delayed-type hypersensitivity test (DTH) responses versus younger controls to
      both phytohemagglutinin-P (PHA; 11.1 +/- 0.95 versus 7.57 +/- 1.15 mm; young
      control versus old-control, respectively; P < .05) and sheep red blood cell (RBC;
      9.12 +/- 0.62 versus 8.08 +/- 0.75 mm; young-control versus old-control,
      respectively; P < .10). beta-Carotene improved these responses, mostly within the
      first 24-48 hours after injection. In summary, older dogs have lower
      immunological responses compared with younger controls. beta-Carotene
      supplementation significantly restored immune responses in older dogs when
      compared with their age-matched controls and younger counterparts.

PMID- 14658722
TI  - Rhinitis/Bronchopneumonia syndrome in Irish Wolfhounds.
AB  - This study describes the clinical, immunologic, genetic, and pathologic features
      of Irish Wolfhounds with rhinitis/bronchopneumonia syndrome. The dogs examined
      were from Belgium, The Netherlands, UK, Canada, Germany, and Switzerland. Signs
      included transient to persistent mucoid or mucopurulent rhinorrhea, cough, and
      respiratory dyspnea. Radiographic, rhinoscopic, and bronchoscopic findings were
      variable. Analysis of ciliary ultrastructure was performed in 5 affected dogs,
      but no characteristic primary ciliary defects (primary ciliary dyskinesia) were
      detected. Serum and bronchoalveolar lavage fluid (BALF) concentrations of IgA,
      IgG, and IgM were determined in some affected dogs and clinically normal Irish
      Wolfhounds. Serum IgA concentration was below the reference range in 5 of 8
      affected dogs tested, whereas BALF IgA concentration was above the normal range
      in 2 affected adult dogs. The CD4 to CD8 lymphocyte subset ratio (CD4:CD8) in
      peripheral blood was tested in 3 affected dogs and was within the normal range.
      BALF CD4:CD8 was tested in 1 affected dog and was higher than the normal range.
      Decreased neutrophil phagocytosis was observed in 1 of the 4 dogs tested.
      Analysis of pedigrees of the Belgian, Canadian, German, and Swiss dogs revealed
      common ancestry, suggesting a heritable syndrome.

PMID- 14658723
TI  - Feline intracranial neoplasia: retrospective review of 160 cases (1985-2001).
AB  - The purpose of this study was to determine the frequency of different tumor types
      within a large cohort of cats with intracranial neoplasia and to attempt to
      correlate signalment, tumor size and location, and survival time for each tumor.
      Medical records of 160 cats with confirmed intracranial neoplasia evaluated
      between 1985 and 2001 were reviewed. Parameters evaluated included age, sex,
      breed, FeLV/FIV status, clinical signs, duration of signs, number of tumors,
      tumor location(s), imaging results, treatment, survival times, and
      histopathologic diagnosis. Most of the cats were older (11.3 +/- 3.8 years).
      Primary tumors accounted for 70.6% of cases. Metastasis and direct extension of
      secondary tumors accounted for only 5.6 and 3.8% of cases, respectively. Twelve
      cats (7.5%) had 2 or more discrete tumors of the same type, whereas 16 cats
      (10.0%) had 2 different types of intracranial tumors. The most common tumor types
      were meningioma (n = 93, 58.1%), lymphoma (n = 23, 14.4%), pituitary tumors (n =
      14, 8.8%), and gliomas (n = 12, 7.5%). The most common neurological signs were
      altered consciousness (n = 42, 26.2%), circling (n = 36, 22.5%), and seizures (n
      = 36, 22.5%). Cats without specific neurological signs were common (n = 34,
      21.2%). The tumor was considered an incidental finding in 30 (18.8%) cats. In
      addition to expected relationships (eg, meninges and meningioma, pituitary and
      pituitary tumors), we found that lesion location was predictive of tumor type
      with diffuse cerebral or brainstem involvement predictive of lymphoma and third
      ventricle involvement predictive of meningioma.

PMID- 14658724
TI  - Hypomagnesemia in hospitalized horses.
AB  - This study was initiated to identify the signalment and clinical variables
      potentially associated with hypomagnesemia in horses evaluated at the North
      Carolina State University, College of Veterinary Medicine (NCSU-CVM) veterinary
      teaching hospital between January 1999 and May 2001. A nested case reference
      study (nested case-control study) was conducted to examine the potential
      relationship between hypomagnesemia and signalment, serum chemistry panel
      analyses, number of hospitalization days, discharge status, and diagnosis. A
      series of independent and multivariable logistic regression models were used to
      assess the potential association of each variable with low total serum magnesium
      concentrations. Four hundred one of 823 (48.7%) horses had serum total magnesium
      concentrations below the normal reference range. Hypomagnesemia was more likely
      to occur in horses older than I month of age. Colic (odds ratio [OR]: 2.96, 95%
      confidence intervals [CI]: 2.14-4.08), acute diarrhea (OR: 5.91, 95% CI: 2.32
      15.06), other gastrointestinal disease (OR: 2.07, 95% CI: 1.15-3.71), infectious
      respiratory disease (OR: 5.07, 95% CI: 2.09-12.28), and multiorgan system disease
      (OR: 2.31, 95% CI: 1.24-4.28) were associated with hypomagnesemia in adult
      horses, whereas foals with diarrhea (excluding septic foals) (OR: 0.11, 95% CI:
      0.01-0.84) were less likely to have hypomagnesemia. Overall, there was no
      relationship between hypomagnesemia and mortality (OR: 1.00, 95% CI: 0.72-1.41),
      but horses with colic and hypomagnesemia were less likely to die than horses with
      colic and normal or high total magnesium (OR: 0.53, 95% CI: 0.30-0.95). Among
      horses that survived, hypomagnesemia at admission was associated with a longer
      hospitalization period (OR: 1.45, 95% CI: 1.00-2.11).

PMID- 14658725
TI  - Risk factors and prognostic variables for survival of foals with radiographic
      evidence of pulmonary disease.
AB  - The medical records of 163 neonatal foals that had thoracic radiographs taken
      within 48 hours of admission to a referral hospital were reviewed. The objectives
      of this study were (1) to identify risk factors for the development of thoracic
      radiographic changes and (2) to identify prognostic indicators for survival in
      foals with radiographic evidence of pulmonary disease. Failure of transfer of
      passive immunity (IgG concentration < or = 400 mg/dL) was the only risk factor
      for radiographic evidence of respiratory disease identified by multivariate
      analysis. Hypoxemic patients (PaO2 < or = 60 mm Hg) were 4.9 times more likely to
      reveal radiographic abnormalities in a subset of foals for which arterial blood
      gas results were available. Foals with a serum creatinine concentration > 1.7
      mg/dL upon presentation, dyspnea, and a history of dystocia were significantly
      more likely to die based on the multivariate statistical outcome analysis. An
      anion gap > or = 20 mEq/dL was strongly associated with nonsurvival in a subset
      of foals with arterial blood gas results. These hematologic and biochemical
      variables can be readily obtained during the initial evaluation of sick foals.
      The presence of a high anion gap appeared to have the greatest clinical impact
      and may be a useful prognostic indicator in foals with radiographic evidence of
      respiratory disease. In contrast, the majority of physical examination variables,
      including evaluation of tachypnea, abnormal respiratory sounds, fever, weakness,
      and milk reflux from the nares, which are usually obtained during the general
      respiratory evaluation of foals, were unrelated to outcome.

PMID- 14658726
TI  - Clinical and prognostic significance of radiographic pattern, distribution, and
      severity of thoracic radiographic changes in neonatal foals.
AB  - A total of 207 thoracic radiographs obtained from 128 foals were evaluated to
      assess the impact of pulmonary radiographic pattern, distribution, and severity
      of pulmonary changes on short-term survival of neonatal foals. The association
      between selected clinical variables and the radiographic manifestation of
      neonatal respiratory disease was also investigated. The evaluation of
      interstitial and alveolar-interstitial radiographic patterns within the
      caudodorsal, caudoventral, and cranioventral lung regions proved to be highly
      reliable between viewers in the study. A diagnosis of systemic inflammatory
      response syndrome was related to increased pulmonary infiltrates within the
      caudodorsal lung region. Dyspneic foals had more extensive pulmonary infiltrates
      within the cranioventral lung, advanced respiratory disease, and lower survival
      rates. A fibrinogen concentration >400 mg/dL was associated with increased
      cranioventral radiographic abnormalities. In addition, tachypnea most
      consistently related to diffuse (caudodorsal, caudoventral, and cranioventral)
      pulmonary changes. Neutropenia, milk reflux from the nares, upper airway
      pathology, abnormal respiratory sounds, failure of transfer of passive immunity
      (IgG concentration <400 mg/dL), immaturity, or fever, however, were not related
      to radiographic pattern, distribution, or severity of radiographic changes. Sixty
      five percent of foals with radiographic pulmonary disease were discharged alive
      from our referral hospital. Concurrent caudodorsal and caudoventral radiographic
      disease was most frequently observed in this foal population. Increased
      caudodorsal radiographic scores retained statistical significance as a prognostic
      indicator for nonsurvival in a multiple stepwise logistic regression analysis.

PMID- 14658727
TI  - Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy
      and reduced side effects.
AB  - Continuous rate infusion (CRI) of furosemide in humans is considered superior to
      intermittent administration (IA). This study examined whether furosemide CRI,
      compared with IA, would increase diuretic efficacy with decreased fluid and
      electrolyte fluctuations and activation of the renin-angiotensin-aldosterone
      system (RAAS) in the horse. Five mares were used in a crossover-design study.
      During a 24-hour period, each horse received a total of 3 mg/kg furosemide by
      either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1
      mg/kg IV q8h). There was not a statistically significant difference in urine
      volume over 24 hours between methods; however, urine volume was significantly
      greater after CRI compared with IA during the first 8 hours ([median 25th
      percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0]
      for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma
      volume, and suppressed renal concentrating ability throughout the infusion
      period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133
      mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus
      73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457,
      1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47
      hours for CRI and IA, respectively. The area under the excretion rate curve was
      1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12
      mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended
      when profound diuresis is needed acutely in horses.

PMID- 14658728
TI  - A retrospective analysis of hepatic injury in horses with proximal enteritis
      (1984-2002).
AB  - The purpose of this study was to test the hypothesis that horses with proximal
      enteritis (PE) are predisposed to hepatic injury. We also determined whether the
      presence of liver injury in horses with PE was associated with other
      clinicopathologic abnormalities or affected outcome. The medical records of all
      horses admitted for evaluation of colic and gastric reflux between 1984 and 2002
      were reviewed. Horses were considered to have PE if the diagnosis was made at
      surgery or postmortem examination or if they had clinical findings consistent
      with PE. Horses with a small intestinal strangulating obstruction (SISO) were
      used as the control group. Historic and clinicopathologic data were collected for
      each horse. The data were analyzed by descriptive statistics, parametric and
      nonparametric analyses, and logistic regression. Horses with PE had significantly
      higher serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST),
      and alkaline phosphatase (ALP) activities than horses with SISO (P < .05). Horses
      with PE were 12.1 times more likely to have high GGT activities than were horses
      with SISO. Horses with PE had an increased risk of at least 1 hepatic enzyme
      being increased if a high anion gap or large volume of reflux was present. Our
      conclusion is that horses with PE are more likely to have hepatic injury than
      horses with SISO. The mechanism of hepatic injury may involve ascending infection
      from the common bile duct, absorption of endotoxin or inflammatory mediators from
      the portal circulation, or hepatic hypoxia resulting from systemic inflammation
      and endotoxemic shock.

PMID- 14658729
TI  - The relationship between endogenous cortisol, blood micronutrients, and
      neutrophil function in postparturient Holstein cows.
AB  - Neutrophil function, blood micronutrients, and cortisol concentrations were
      measured in 43 clinically healthy postparturient Holstein cows. Estimated 305-day
      mature equivalent milk production and neutrophil function were related to results
      of the blood micronutrient concentrations and neutrophil function tests. Cattle
      had low to normal zinc concentrations; normal to high selenium, vitamin E, and
      cortisol concentrations; and normal copper concentrations. Blood selenium (P =
      .03) and zinc (P = .027) concentrations were both significant predictors of
      neutrophil adhesion, and selenium (P < .001) was a significant predictor of
      neutrophil cytochrome C reduction (superoxide production). Fourteen of 20 (70%)
      cattle with blood selenium concentrations > 300 ng/mL had neutrophil adhesion,
      and 15 of 20 (75%) had cytochrome C reduction above the mean value for this
      group. There was also a significant correlation (r = 0.331; P = .037) between
      cytochrome C reduction and estimated milk production. These findings suggest that
      neutrophils from postparturient dairy cows with higher blood concentrations of
      selenium have greater potential to kill microbes, and that cattle with greater
      superoxide production may have higher milk production.

PMID- 14658730
TI  - The clinical neurology of scrapie in Irish sheep.
AB  - One hundred twenty-nine sheep with scrapie were identified from 20 flocks in
      which scrapie previously had been confirmed. Physical and neurologic examinations
      were performed on all animals. Videotape recordings were made and reviewed to
      assess gait. These procedures were repeated in 46 sheep at 2- to 3-week intervals
      until recumbency or inappetence necessitated euthanasia. Confirmation of scrapie
      was made by histopathologic and immunohistochemical examinations of brain tissue.
      The clinical signs most frequently recorded in the 129 animals on initial
      presentation were hindlimb ataxia (71%), head tremor (61%), altered mental status
      (57%), positive nibble reflex (51%), crouching posture (51%), teeth grinding
      (44%), low head carriage (38%), body condition score (BCS) < 1.5 (38%), and
      conscious proprioceptive deficits of the hindlimbs (36%). Progression of the
      disease was characterized by an increase in the frequency and severity of ataxia,
      weakness and hypermetria of the hindlimbs, a decreasing sway response, a
      decreasing extensor response to thoracolumbar pressure, and a reduction in the
      BCS. No effect of farm of origin on the clinical presentation could be shown. The
      presence of a nibble reflex was strongly associated (P < .0005) with prion
      protein (PrP) genotypes AA136RR154QH171 and AA136RR154QQ171. Logistic regression
      modeling of groups with associated clinical signs showed that animals with a
      crouching posture (odds ratio [OR], 20.036) and an abnormal yield to
      thoracolumbar pressure (OR, 7.117) were at increased risk of ataxia. Pruritus
      (OR, 0.168) was negatively associated with ataxia. Pruritus (OR, 4.974) and teeth
      grinding (OR, 4.279) were associated with a positive nibble reflex.

PMID- 14658731
TI  - Aortic thromboembolism and retroperitoneal hemorrhage associated with a
      pheochromocytoma in a dog.

PMID- 14658732
TI  - Pericardial effusion due to primary cardiac lymphosarcoma in a dog.

PMID- 14658733
TI  - Balloon valvuloplasty in a cat with pulmonic stenosis.

PMID- 14658734
TI  - A hemolytic transfusion reaction due to DEA 4 alloantibodies in a dog.

PMID- 14658735
TI  - Clostridium novyi type A intra-abdominal abscess in a horse.

PMID- 14658736
TI  - Colocolic intussusception in a 12-year-old llama.

PMID- 14658737
TI  - Anion gap correlates with serum D- and DL-lactate concentration in diarrheic
      neonatal calves.
AB  - The objective of this study was to investigate the relationship between serum D-
      and L-lactate concentrations, and anion gap (AG) in neonatal calves. The
      association of AG with lactic acidosis in diarrheic calves has only been
      investigated by measurement of L-lactate in calves with experimentally induced
      diarrhea. D-lactate has recently been reported to be present in high
      concentrations in the serum of some diarrheic neonatal calves. The contribution
      of this acid to AG is not reported. The relationship between AG and L- and D
      lactate concentrations was examined in 24 healthy calves and 52 calves with
      naturally occurring infectious diarrhea with metabolic acidosis. AG was
      calculated as [Na+ + K+] - [Cl- + HCO3-]. D- and L-lactate were quantified using
      high-performance liquid chromatography. There was no correlation between L
      lactate and AG, contrary to previous reports in the literature. Moderate
      correlations between D-lactate concentration and AG (r = .74, P < .0001), and
      between DL-lactate and AG (r = .77), P < .0001) were detected. No differences
      existed due to the age or sex of the calf. This study indicates that AG provides
      information on the nature of acidosis in the diarrheic, neonatal calf and
      reinforces the importance of investigating clinical, in addition to experimental,
      populations.

PMID- 14658738
TI  - Developmental timing of exposure to elevated levels of phenylalanine is
      associated with ADHD symptom expression.
AB  - This study addresses attention deficit hyperactivity disorder (ADHD), with a
      focus on how the timing of a known biological insult affects ADHD symptom
      expression. The sample consists of children exposed to elevated levels of
      phenylalanine, either postnatally as in Phenylketonuria (PKU; n = 46) or
      prenatally as in Maternal PKU (MPKU; n = 15). Non-hyperphenylalaninemic siblings
      of children with PKU (n = 18) serve as controls. Results indicate that elevated
      levels of phenylalanine are associated with ADHD symptoms. The manifestations of
      the symptom expression are dependent on exposure timing: prenatal exposure is
      associated with a higher likelihood of expressing hyperactive/impulsive symptoms
      and postnatal exposure is associated with a higher likelihood of expressing
      inattentive symptoms. This toxicity is dose-dependent and higher levels of
      phenylalanine appear more detrimental.

PMID- 14658739
TI  - Predicting growth curves of externalizing behavior across the preschool years.
AB  - Hierarchical linear modeling was used to examine 2 facets of externalizing
      behavior: its level at age 6 and its rate of change from age 2 to 6 among 299
      boys from low-income families. As for age-6 level of externalizing behavior,
      maternal depressive symptoms, maternal acceptance of child behavior, parental
      conflict, and the interaction between maternal acceptance and maternal depressive
      symptoms were each uniquely associated with this outcome. Regarding the
      interaction, maternal acceptance was associated with externalizing behavior
      primarily when maternal depressive symptoms were low, and maternal depressive
      symptoms were related to externalizing behavior only when maternal acceptance was
      high. Externalizing behavior gradually decreased between ages 2 and 6;
      interactions between infant negative emotionality and maternal depressive
      symptoms and between parental conflict and maternal acceptance were associated
      with rate of change. Plots suggested a protective effect of low infant negative
      emotionality when maternal depressive symptoms were high and a larger effect of
      maternal acceptance when parental conflict was low compared to when it was high.
      Results add to a small but growing literature regarding predictors of continuity
      and change in early child externalizing behavior.

PMID- 14658740
TI  - Neighborhood violence and coparent conflict: interactive influence on child
      psychosocial adjustment.
AB  - The interactive influence of neighborhood violence and coparent conflict on child
      psychosocial adjustment was examined in a sample of 117 low-income, inner-city
      African American families. Data were collected and analyzed cross-sectionally and
      longitudinally. Lower levels of coparent conflict buffered girls, but not boys,
      from the detrimental effects of living in neighborhoods characterized by high
      levels of violence. In both cross-sectional and longitudinal analyses, lower
      levels of coparent conflict, relative to higher levels, protected girls from
      depressive symptoms and aggressive behaviors in the context of higher levels of
      neighborhood violence. Clinical implications of the findings and directions for
      future research are discussed.

PMID- 14658741
TI  - Deviant peer affiliations and depression: confounding or causation?
AB  - Data gathered from 2 longitudinal studies (the Christchurch Health and
      Development study of a birth cohort of 1,265 New Zealand participants studied to
      21 years and the Quebec Study of 240 Canadian participants studied to 13 years)
      was used to examine the linkages between deviant peer affiliations and depression
      in adolescence. Both studies produced similar conclusions: a) increasing peer
      affiliations were associated with significant (p < .0001) increases in depressive
      symptoms; b) the associations between peer affiliations and depression could not
      be fully explained by confounding factors; and c) peer affiliations and
      depressive symptoms were linked by a causal chain process in which deviant peer
      affiliations led to increased externalizing behaviors with the negative
      consequences of these behaviors leading to depression.

PMID- 14658742
TI  - Friends as reporters of children's and adolescents' depressive symptoms.
AB  - Obtaining information from multiple informants is important when assessing youth
      depression. Past studies have utilized adults' reports of youths' emotional
      functioning and aggregate reports from classmates but have not considered close
      friends as reporters of depressive symptoms. This is surprising given the
      important roles of friends as companions and confidants. This study investigated
      relations between friend-reported depressive symptoms and youths' self-reports.
      From a larger sample of fifth-, seventh-, and ninth-grade participants, self
      reports and friend reports of depressive symptoms and friend reports of
      friendship quality were available for a subset of 367 participants. Significant
      positive relations emerged between friend reports and self-reports of affective
      depressive symptoms for girls and youth in high-quality friendships. Relations
      between friend reports and self-reports were stronger for conduct-related than
      affective depressive symptoms and reached significance for boys as well as for
      girls and for youth in low-quality friendships as well as for youth in high
      quality friendships. Implications for identifying at-risk youth are discussed.

PMID- 14658743
TI  - Genetic and environmental influences on psychopathy trait dimensions in a
      community sample of male twins.
AB  - Psychopathy appears to be comprised of two broad dimensions:
      impulsivity/antisocial behavior and interpersonal detachment/callousness. This
      study examined the extent to which variance in these 2 psychopathy trait
      dimensions was associated with common or unique genetic, shared, and nonshared
      environmental factors in two independent samples of reared together 16-18-year
      old male twins. One sample included 142 monozygotic (MZ) and 70 dizygotic (DZ)
      pairs; the other sample included 128 MZ and 58 DZ pairs. Boys completed the
      Minnesota Temperament Inventory (MTI), a 19-item measure that contains separate
      subscales: Antisocial and Detachment. Variance in the Antisocial and Detachment
      scales was associated with additive genetic factors and neither scale was
      associated with shared environmental factors. As expected, the bivariate
      biometric analysis suggested genetic influence on the covariance of the scales.
      The results are consistent with theoretical models of psychopathy that posit some
      independence in the etiology of the two major trait dimensions of psychopathy.

PMID- 14658744
TI  - Subfactors of DSM-IV conduct disorder: evidence and connections with syndromes
      from the Child Behavior Checklist.
AB  - Is conduct disorder (CD) as defined in the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV; American Psychiatric Association, 1994) a unitary
      entity, or do variants of CD exist? We addressed this question, using data
      collected from the parents of 1,669 Australian boys, aged 6-17. Parents were
      interviewed to assess DSM-IV Conduct Disorder (DSM-IV CD) criteria. Results
      revealed 2 subfactors of DSM-IV CD symptoms, made up of overt behaviors (e.g.,
      initiating physical fights) and covert behaviors (e.g., stealing without
      confrontation). Ordinary least squares regressions showed the 2 CD subfactors to
      be significantly and uniquely predicted by Child Behavior Checklist (CBCL; T. M.
      Achenbach, 1991a, 1991b) syndromes labeled Aggressive Behavior and Delinquent
      Behavior, respectively. The results are discussed in terms of the utility of
      differentiating these 2 variants of CD in future editions of the DSM.

PMID- 14658745
TI  - The emergence of ethnic and racial attitudes in preschool-aged children.
AB  - The author assessed preschool-aged children's attitudes (N = 70) toward their own
      and 2 ethnic or racial out-groups using traditional forced-choice measures and a
      new method that assessed children's out-group attitudes independently of their
      attitudes toward their own group. When required to assign positive and negative
      traits to either their own group or an ethnic or racial out-group, children
      evaluated their own group favorably relative to the out-group in question.
      However, when not forced to choose between groups, children evaluated out-groups
      positively, indicating that own-group preference relative to ethnic and racial
      out-groups was not equated with out-group rejection. Children's positive out
      group evaluations did vary with the out-group being considered and were
      reflective of the local social context, suggesting the influence of social
      learning. The results indicate that young children's positive feelings toward
      their own group do not necessarily involve or cause negative out-group attitudes
      and that various factors might differentially influence in-group and out-group
      attitudes.

PMID- 14658746
TI  - Automatic activation of Yellow Peril Asian American stereotypes: effects on
      social impression formation.
AB  - The authors randomly assigned 69 undergraduates to 1 of 2 perceptual priming
      conditions involving 80-ms flash words presented on a computer screen to activate
      information processing outside of conscious awareness. In the high-prime
      condition, the authors exposed participants to stereotype words associated with
      the Yellow Peril view of Asian Americans. The authors exposed participants in a
      low-prime condition to neutral words. All participants then read a vignette and
      evaluated its protagonist on several social dimensions. Results indicated that
      the priming procedure effectively biased participant evaluation of the vignette
      target, but only on items closely linked to Asian Americans. Contrary to
      predictions, however, participants in the high-prime group rated the target less
      Asian than did their low-prime group counterparts, an apparent reversal of the
      expected priming effect. The authors discussed theoretical implications.

PMID- 14658747
TI  - The process of coping among ethnic minority first-generation college freshmen: a
      narrative approach.
AB  - Using a narrative approach, the authors explored the process of coping among
      ethnic minority college students. Participants were 30 freshmen, predominantly
      the 1st members of their families to attend college, who wrote journals once a
      week for 3 weeks on their ways of coping with stress. They also completed a
      survey of background information. Those who were more successful in coping,
      compared to those who were less successful, expressed a greater sense of self
      efficacy and did not feel that they lacked needed social support. However, those
      who were more successful in coping did not differ on demographic variables,
      including ethnicity, gender, country of birth, and parental education. The
      narratives provide evidence of the complex and interactive process of coping
      among ethnic minority college students.

PMID- 14658748
TI  - What predicts adjustment among law students? A longitudinal panel study.
AB  - Although at the time of this article's publication, many anecdotes and cross
      sectional studies had reported that law students experience significant distress
      during their 1st year, few researchers had controlled for prelaw school status
      (e.g., M. Garrison, B. Tomko, & I. Yip, 1996; L. Guinier, M. Fine, J. Balin, A.
      Bartow, & D. L. Stachel, 1994), and only a single group of researchers had
      explored a psychosocial factor that predicted these changes. The present authors
      tested 3 sets of potential predictors of adjustment: sources of stress, coping
      strategies, and relationship factors. The present data replicated declines in
      students' psychological health, physical health, and attitudes toward law over
      the 1st year of school. That result supports the generalizability and currency of
      previous studies. In contrast to other researchers, the present authors found few
      gender differences. Less relationship happiness, less emotional support, and use
      of less active coping tactics at the beginning of the year predicted poorer
      outcomes at the end of the year. Strain from academic pressures, lack of personal
      time, and social isolation were correlated with poorer outcomes.

PMID- 14658749
TI  - Reciprocated and unreciprocated dyadic peer preferences and academic achievement
      of Israeli and immigrant students: a longitudinal study.
AB  - The authors used a longitudinal design to investigate 2 major issues: first,
      whether popularity with classmates results in better academic achievement or
      academic achievement improves popularity with classmates; and second, how time
      affects in-group and out-group contacts in the elementary school. The authors
      studied these issues by means of an interactive measure of reciprocated and
      unreciprocated contacts with peers. This measure indicated the extent to which
      aspirations for close relations were fulfilled or not fulfilled by each member of
      a dyad. Participants were 305 fifth- and sixth-grade Israeli students and 100
      immigrant classmates. Results indicated (a) higher academic achievement predicted
      higher numbers of bids for reciprocal contacts in class but not higher numbers of
      bids for contacts that were not reciprocated; (b) a higher level of
      unreciprocated bids for contact seemed to have a detrimental effect on academic
      performance; (c) teachers tended to rate as more adjusted to school the immigrant
      students who were willing to engage in more intensive reciprocated contacts with
      Israeli peers; and (d) reciprocated contacts tended to increase whereas
      unreciprocated contacts were inclined to decrease as a function of time. These
      changes over time were more prominent for the dominant hosts than for their
      migrant classmates.

PMID- 14658750
TI  - Extending the theory of realistic conflict to competition in institutional
      settings: intergroup status and outcome.
AB  - The authors analyzed the extent to which the Theory of Realistic Conflict can be
      extended to institutional settings in which groups are not actively involved in
      decisions but are passive targets of decisions taken by an institutional
      authority (the rector). A negative interdependence between the in-group
      (psychology) and a high- or low-status outgroup (engineering versus nursing) was
      established by an institutional authority (the rector). The competition (induced
      by the rector) was beneficial (an increase in the budget previously invested in
      the faculty) or detrimental (a decrease in the budget) for the in-group. The
      results confirmed that competition affects mutual attitudes, images, and
      behaviors of groups even if the groups are passive targets of decisions that the
      institutional authority makes. Moreover, competition--regardless of whether
      beneficial or detrimental--deteriorated images of and attitudes toward high
      status out-groups. In contrast, competition improved images and opinions about
      low-status out-groups, but only in the loss condition.

PMID- 14658751
TI  - Positive-negative asymmetry in the evaluation of trivial stimuli.

PMID- 14658752
TI  - Tactile contact and spontaneous help: an evaluation in a natural setting.

PMID- 14658753
TI  - A social identity perspective on the relationship between perceived
      organizational support and organizational commitment.

PMID- 14658754
TI  - Emotional reactions toward procedural fairness as a function of negative
      information.

PMID- 14658755
TI  - Putting the brake on inflammatory responses: the role of glucocorticoids.
AB  - Glucocorticoids are among the most widely used agents for the treatment of
      inflammatory diseases. The primary mechanism of glucocorticoid action is via the
      glucocorticoid receptor (GR), which blocks the expression of proinflammatory
      cytokines and adhesion molecules. Repression of many pro-inflammatory genes
      occurs by inhibition of transcription factors including nuclear factor kappaB
      (NFkappaB) and activator protein-1 (AP-1). In this article, we discuss the
      physiological and molecular interaction that occurs between GR and
      proinflammatory cytokines signaling pathways.

PMID- 14658756
TI  - Properties of human mitochondrial ribosomes.
AB  - Mammalian mitochondrial ribosomes (55S) differ unexpectedly from bacterial (70S)
      and cytoplasmic ribosomes (80S), as well as other kinds of mitochondrial
      ribosomes. Typical of mammalian mitochondrial ribosomes, the bovine mitochondrial
      ribosome has been developed as a model system for the study of human
      mitochondrial ribosomes, to address several questions related to the structure,
      function, biosynthesis and evolution of these interesting ribosomes. Bovine
      mitochondrial ribosomal proteins (MRPs) from each subunit have been identified
      and characterized with respect to individuality and electrophoretic properties,
      amino acid sequence, topographic disposition, RNA binding properties,
      evolutionary relationships and reaction with affinity probes of ribosomal
      functional domains. Several distinctive properties of these ribosomes are being
      elucidated, including their antibiotic susceptibility and composition. Human
      mitochondrial ribosomes lack several of the major RNA stem structures of
      bacterial ribosomes but they contain a correspondingly higher protein content (as
      many as 80 proteins), suggesting a model where proteins have replaced RNA
      structural elements during the evolution of these ribosomes. Despite their lower
      RNA content they are physically larger than bacterial ribosomes, because of the
      'extra' proteins they contain. The extra proteins in mitochondrial ribosomes are
      'new' in the sense that they are not homologous to proteins in bacterial or
      cytoplasmic ribosomes. Some of the new proteins appear to be bifunctional. All of
      the mammalian MRPs are encoded in nuclear genes (a separate set from those
      encoding cytoplasmic ribosomal proteins) which are evolving more rapidly than
      those encoding cytoplasmic ribosomal proteins. The MRPs are imported into
      mitochondria where they assemble coordinately with mitochondrially transcribed
      rRNAs into ribosomes that are responsible for translating the 13 mRNAs for
      essential proteins of the oxidative phosphorylation system.

PMID- 14658757
TI  - Solid-state NMR structure determination.
AB  - Biological applications of solid-state NMR (SS-NMR) have been predominantly in
      the area of model membrane systems. Increasingly the focus has been membrane
      peptides and proteins. SS-NMR is able to provide information about how the
      peptides or proteins interact with the lipids or other peptides/proteins in the
      membrane, their effect on the membrane and the location of the peptides or
      proteins relative to the membrane surface. Recent developments in biological SS
      NMR have been made possible by improvements in labelling and NMR techniques. This
      review discusses aligned systems and magic angle spinning techniques, bilayers
      and bicelles, and measurement of chemical shift anisotropy and dipolar coupling.
      A number of specific experiments such as cross polarization, rotational
      resonance, REDOR, PISEMA, MAOSS and multidimensional experiments are described.
      In addition to 2H, 13C and 15N, recent solid-sate 1H, 19F and 17O NMR work is
      discussed. Several examples of the use of SS-NMR to determine the structure of
      membrane peptides and proteins are given.

PMID- 14658758
TI  - Evidence for heme oxygenase-1 association with caveolin-1 and -2 in mouse
      mesangial cells.
AB  - The interaction of heme oxygenase-1 (HO-1) and caveolin in the cultured mouse
      mesangial cells (MMC) was investigated. In normal MMCs, high levels of caveolin-2
      and low level of caveolin-1 at mRNA and protein level were observed without any
      detectable expression of caveolin-3. Upon treating the MMCs either with cadmium
      (Cd) or spermine NONOate (SPER/NO), expression of HO-1 mRNA and protein was
      increased. Caveolae rich membranous fractions from the MMCs treated with Cd or
      SPER/NO contained both HO-1 and caveolin-1 or caveolin-2. The experiments of
      immuno-precipitation showed complex formation between the HO-1 and caveolin-1 or
      caveolin-2 in the Cd treated MMCs. Confocal microscopic results also support co
      localization of HO-1 and caveolin-1 or caveolin-2 at the plasma membrane. Co
      localization of caveolins with HO-1 in caveolae suggested that caveolin could
      also play an important role in regulating the function of HO-1.

PMID- 14658759
TI  - Capn10, a candidate gene responsible for type 2 diabetes mellitus in the OLETF
      rat.
AB  - The rat strain Otsuka Long-Evans Tokushima Fatty (OLETF) is an animal model for
      type 2 diabetes mellitus. Nidd8/of has been identified as one of 14 quantitative
      trait loci (QTLs) involved in the diabetes by a whole genome search in 160 F2
      progenies obtained by mating the OLETF and F344 rats. Comparative mapping between
      human and rat indicated that the Nidd8/of genomic region, near D9rat21 on rat
      chromosome 9, contains the calpain10 (Capn10) gene, which is putative type 2
      diabetes-susceptibility gene in humans. In this study, we found no difference in
      Capn10 mRNA expression in the heart, liver, skeletal muscle and pancreas between
      OLETF and F344 rats at 5 and 10 weeks of age. However, we found a single
      nucleotide polymorphism (SNP) (A/A genotype in OLETF and G/G genotype in F344 and
      LETO rats) at the base 583 downstream from the translation start site in the rat
      Capn10 cDNA sequence. This SNP was deduced to substitute serine (OLETF) for
      glycine (F344 and LETO) at the 195 amino acid residue within the protease domain
      of rat Capn10. Because serine is generally not interchangeable with glycine in
      respect of the protein structure and function, it was deduced that the A/A
      genotype in OLETF is not a 'safe' mutation. This non-conservative amino acid
      substitution might be associated with susceptibility to type 2 diabetes in OLETF
      rats.

PMID- 14658760
TI  - Identification and characterization of a serum protein homologous to alpha-type
      phospholipase A2 inhibitor (PLIalpha) from a nonvenomous snake, Elaphe
      quadrivirgata.
AB  - From a liver cDNA library prepared from a nonvenomous striated snake, Elaphe
      quadrivirgata, we isolated a cDNA encoding a novel protein, PLIalpha-like protein
      (PLIalpha-LP), having approximately 70% sequence identities with the alpha-type
      phospholipase A2 (PLA2) inhibitors (PLIalpha(s)) previously purified from the
      venomous snakes Agkistrodon blomhoffii siniticus and Trimeresurus flavoviridis.
      Since the PLI-LP with a highly conserved C-type lectin-like domain (CTLD) would
      be predicted to function as a PLA2 inhibitor, we purified this protein from E.
      quadrivirgata serum by sequential chromatography on Hi-trap Blue, Mono Q, and
      Superdex 200 columns. The purified 51-kDa protein with PLIalpha-like
      immunoreactivity was found to be a trimer of 18-kDa PLIalpha-LP, which was
      comparable to the trimeric structure of PLIalpha. But, unexpectedly, this protein
      did not show any inhibitory activity against various snake venom PLA2s.
      Furthermore, it did not inhibit the endogenous PLA2 activities in various tissue
      homogenates prepared from this snake. Lack of the inhibitory activity in PLIalpha
      LP may provide important information concerning the structure-function
      relationships of PLIalpha.

PMID- 14658761
TI  - The chemical modification of the essential groups of beta-N-acetyl-D
      glucosaminidase from Turbo cornutus Solander.
AB  - The chemical modification of beta-N-acetyl-D-glucosaminidase (EC3.2.1.30) from
      Turbo cornutus Solander has been first studied. The results demonstrate that the
      sulfhydryl group of cysteine residues and the hydroxyl group of serine residues
      are not essential to the enzyme's function. The modification of indole group of
      tryptophan of the enzyme by N-bromosuccinimide (NBS) can lead to the complete
      inactivation, accompanying the absorption decreasing at 278 nm and the
      fluorescence intensity quenching at 335 nm, indicating that tryptophan is
      essential residue to the enzyme. The modification of amino group of lysine
      residue by formaldehyde and trinitrobenzenesulfonic acid also inactivates the
      enzyme completely. The results show that lysine and tryptophan are probably
      situated in the active site of the enzyme. The modification of the imidazole
      residue and carboxyl group leads to inactivate incompletely, indicating they are
      not the composing groups of the enzyme active center, and they are essential for
      maintaining the enzyme's conformation which is necessary for the catalytic
      activity of the enzyme.

PMID- 14658762
TI  - Why is glutathione (a tripeptide) synthesized by specific enzymes while TSH
      releasing hormone (TRH or thyroliberin), also a tripeptide, is produced as part
      of a prohormone protein?

PMID- 14658763
TI  - How I became a biochemist.

PMID- 14658764
TI  - Inhibitory network properties shaping the light evoked responses of cat alpha
      retinal ganglion cells.
AB  - Cat retinal ganglion cells of the Y (or alpha) type respond to luminance changes
      opposite those preferred by their receptive-field centers with a transient
      hyperpolarization. Here, we examine the spatial organization and synaptic basis
      of this light response by means of whole-cell current-clamp recordings made in
      vitro. The hyperpolarization was largest when stimulus spots approximated the
      size of the receptive-field center, and diminished substantially for larger
      spots. The hyperpolarization was largely abolished by bath application of
      strychnine, a blocker of glycinergic inhibition. Picrotoxin, an antagonist of
      ionotropic GABA receptors, greatly reduced the attenuation of the hyperpolarizing
      response for large spots. The data are consistent with a model in which (1) the
      hyperpolarization reflects inhibition by glycinergic amacrine cells of bipolar
      terminals presynaptic to the alpha cells, and perhaps direct inhibition of the
      alpha cell as well; and (2) the attenuation of the hyperpolarization by large
      spots reflects surround inhibition of the glycinergic amacrine by GABAergic
      amacrine cells. This circuitry may moderate nonlinearities in the alpha-cell
      light response and could account for some excitatory and inhibitory influences on
      alpha cells known to arise from outside the classical receptive field.

PMID- 14658765
TI  - Temporal modulation sensitivity of tree shrew retinal ganglion cells.
AB  - Tree shrews (Tupaia belangeri) are small diurnal mammals capable of quick and
      agile navigation. Electroretinographic and behavioral studies have indicated that
      tree shrews possess very good temporal vision, but the neuronal mechanisms
      underlying that temporal vision are not well understood. We used single-unit
      extracellular recording techniques to characterize the temporal response
      properties of individual retinal ganglion cell axons recorded from the optic
      tract. A prominent characteristic of most cells was their sustained or transient
      nature in responding to the flashing spot. Temporal modulation sensitivity
      functions were obtained using a Gaussian spot that was temporally modulated at
      different frequencies (2-60 Hz). Sustained cells respond linearly to contrast.
      They showed an average peak frequency of 6.9 Hz, a high-frequency cutoff at 31.3
      Hz, and low-pass filtering. Transient cells showed nonlinear response to
      contrast. They had a peak frequency of 19.3 Hz, a high-frequency cutoff at about
      47.6 Hz, band-pass filtering, and higher overall sensitivity than sustained
      cells. The responses of transient cells also showed a phase advance of about 88
      deg whereas the phase advance for sustained cells was about 43 deg. Comparison
      with behavioral temporal modulation sensitivity results suggested that transient
      retinal ganglion cells may underlie detection for a wide range of temporal
      frequencies, with sustained ganglion cells possibly mediating detection below 4
      Hz. These data suggest that two well-separated temporal channels exist at the
      retinal ganglion cell level in the tree shrew retina, with the transient channel
      playing a major role in temporal vision.

PMID- 14658766
TI  - Two neuropharmacological types of rabbit ON-alpha ganglion cells express GABAC
      receptors.
AB  - The major inhibitory neurotransmitters GABA and glycine provide the bulk of input
      to large-field ganglion cells in the retina. Whole-cell patch-clamp recordings
      were used to characterize the glycine- and GABA-activated currents for
      morphologically identified ON-alpha ganglion cells in the rabbit retina. Cells
      identified as ON-alpha cells by light evoked currents were intracellularly
      stained and examined by light microscopy which revealed dendritic stratification
      in the vitreal half of the inner plexiform layer and confirmed their
      physiological identity. All Ca(2+)-mediated synaptic influences were abolished
      with Co(2+), revealing two types of ON-alpha cell characterized by their
      different inhibitory current profiles. One group exhibited larger glycine- than
      GABA-activated currents, while the other group had larger GABA- than glycine
      activated currents. Both cell types demonstrated strychnine-sensitive glycine
      activated currents and bicuculline-sensitive GABAA-activated currents.
      Surprisingly, both cell types expressed functional GABAC receptors demonstrated
      by their sensitivity to TPMPA. In addition, the cells with larger glycine
      activated currents also possessed GABAB receptors, whereas those with larger GABA
      activated currents did not. Immunocytochemical experiments confirmed the presence
      of glycine, GABAA, and GABAC receptor subunits on all physiologically identified
      ON-alpha ganglion cells in this study. In addition, the GABAB receptor
      immunolabeled puncta were present on the cells with larger glycine-activated
      currents, but not on the cells with the larger GABA-activated currents. In
      conclusion, the presence of different functional GABA and glycine receptors
      determined physiologically correlated well with the specific GABA and glycine
      receptor immunolabeling for two neuropharmacological types of rabbit ON-alpha
      ganglion cells.

PMID- 14658767
TI  - Connexin 36 in bovine retina: lack of phosphorylation but evidence for
      association with phosphorylated proteins.
AB  - In vertebrate retina interneuronal communication through gap junctions is
      involved in light adaptation and in the transfer of visual information from the
      rod pathway to the cone pathway. Reports over the last two decades have indicated
      that these gap junctions are regulated by cyclic nucleotide-dependent protein
      kinases suggesting that the gap junction proteins, connexins, are phosphorylated.
      Though all the connexins involved in light adaptation and information transfer
      from rod to cone pathway are not yet known, connexin 36 has been shown to be
      definitively involved in the latter process. We have therefore attempted to
      investigate the cyclic nucleotide-dependent phosphorylation of this connexin in
      bovine retina. We found several soluble and membrane proteins in bovine retina
      whose phosphorylation was regulated by cyclic nucleotides. However, no protein of
      about 36 kDa with cyclic nucleotide-regulated phosphorylation was found in gap
      junction-enriched membrane preparations. A 36-kDa phosphorylated protein was
      found in gap junction-enriched membranes phosphorylated in the presence of
      calcium. However, this protein was not immunoprecipitated by anti-connexin 36
      antibodies indicating that it was not connexin 36 in spite of its similarity in
      molecular weight. Immunoprecipitation did reveal phosphorylated proteins
      coimmunoprecipitated with connexin 36. Two of these proteins were identified as
      beta and alpha tubulin subunits. Though cyclic GMP and calcium did not greatly
      influence the association of these proteins with connexin 36, the results suggest
      the possibility of connexin 36 associating with other proteins. Together, these
      observations indicate that interneuronal communication at gap junctions made by
      connexin 36 may not be regulated by direct phosphorylation of connexin 36, but
      possibly by phosphorylation of associated proteins.

PMID- 14658768
TI  - Afferent connectivity to different functional zones of the optic tectum in
      goldfish.
AB  - This work studies the afferent connectivity to different functionally identified
      tectal zones in goldfish. The sources of afferents contributed to different
      degrees to the functionally defined zones. The dorsocentral area of the
      telencephalon was connected mainly with the ipsilateral anteromedial tectal zone.
      At diencephalic levels, neurons were found in three different regions: preoptic,
      thalamic, and pretectal. Preoptic structures (suprachiasmatic and preoptic
      nuclei) projected mainly to the anteromedial tectal zone, whereas thalamic
      (ventral and dorsal) and pretectal (central, superficial, and posterior
      commissure) nuclei projected to all divisions of the tectum. In the
      mesencephalon, the mesencephalic reticular formation, torus longitudinalis, torus
      semicircularis, and nucleus isthmi were, in the anteroposterior axis,
      topographically connected with the tectum. In addition, neurons in the
      contralateral tectum projected to the injected zones in a symmetrical point-to
      point correspondence. At rhombencephalic levels, the superior reticular formation
      was connected to all studied tectal zones, whereas medial and inferior reticular
      formations were connected with medial and posterior tectal zones. The present
      results support a different quantitative afferent connectivity to each tectal
      zone, possibly based on the sensorimotor transformations that the optic tectum
      carries out to generate orienting responses.

PMID- 14658769
TI  - The thermal contribution to photoactivation in A2 visual pigments studied by
      temperature effects on spectral properties.
AB  - Effects of temperature on the spectral properties of visual pigments were
      measured in the physiological range (5-28 degrees C) in photoreceptor cells of
      bullfrog (Rana catesbeiana) and crucian carp (Carassius carassius). Absorbance
      spectra recorded by microspectrophotometry (MSP) in single cells and sensitivity
      spectra recorded by electroretinography (ERG) across the isolated retina were
      combined to yield accurate composite spectra from ca. 400 nm to 800 nm. The four
      photoreceptor types selected for study allowed three comparisons illuminating the
      properties of pigments using the dehydroretinal (A2) chromophore: (1) the two
      members of an A1/A2 pigment pair with the same opsin (porphyropsin vs. rhodopsin
      in bullfrog "red" rods); (2) two A2 pigments with similar spectra (porphyropsin
      rods of bullfrog and crucian carp); and (3) two A2 pigments with different
      spectra (rods vs. long-wavelength-sensitive (L-) cones of crucian carp).
      Qualitatively, the temperature effects on A2 pigments were similar to those
      described previously for the A1 pigment of toad "red" rods. Warming caused an
      increase in relative sensitivities at very long wavelengths but additionally a
      small shift of lambdamax toward shorter wavelengths. The former effect was used
      for estimating the minimum energy required for photoactivation (Ea) of the
      pigment. Bullfrog rod opsin with A2 chromophore had Ea = 44.2 +/- 0.9 kcal/mol,
      significantly lower (one-tailed P < 0.05) than the value Ea = 46.5 +/- 0.8
      kcal/mol for the same opsin coupled to A1. The A2 rod pigment of crucian carp had
      Ea = 42.3 +/- 0.6 kcal/mol, which is significantly higher (one-tailed P < 0.01)
      than that of the L-cones in the same retina (Ea = 38.3 +/- 0.4 kcal/mol), whereas
      the difference compared with the bullfrog A2 rod pigment is not statistically
      significant (two-tailed P = 0.13). No strict connection between lambdamax and Ea
      appears to exist among A2 pigments any more than among A1 pigments. Still, the A1
      --> A2 chromophore substitution in bullfrog opsin causes three changes correlated
      as originally hypothesized by Barlow (1957): a red-shift of lambdamax, a decrease
      in Ea, and an increase in thermal noise.

PMID- 14658770
TI  - The chromatic input to global motion perception.
AB  - For over 30 years there has been a controversy over whether color-defined motion
      can be perceived by the human visual system. Some results suggest that there is
      no chromatic motion mechanism at all, whereas others do find evidence for a
      purely chromatic motion mechanism. Here we examine the chromatic input to global
      motion processing for a range of color directions in the photopic luminance
      range. We measure contrast thresholds for global motion identification and simple
      detection using sparse random-dot kinematograms. The results show a discrepancy
      between the two chromatic axes: whereas it is possible for observers to perform
      the global motion task for stimuli modulated along the red-green axis, we could
      not assess the contrast threshold required for stimuli modulated along the
      yellowish-violet axis. The contrast required for detection for both axes,
      however, are well below the contrasts required for global motion identification.
      We conclude that there is a significant red-green input to global motion
      processing providing further evidence for the involvement of the parvocellular
      pathway. The lack of S-cone input to global motion processing suggests that the
      koniocellular pathway mediates the detection but not the processing of complex
      motion for our parameter range.

PMID- 14658771
TI  - The gap junction blockers carbenoxolone and 18beta-glycyrrhetinic acid antagonize
      cone-driven light responses in the mouse retina.
AB  - Gap junctions are widely expressed throughout the retina, and play an important
      role in the processing of visual information. It has been proposed that
      horizontal cells express unpaired gap junctions, or hemichannels, in their
      dendrites, and that current flowing through hemichannels reduces transmembrane
      voltage at cone terminals, promoting the opening of Ca2+ channels near sites of
      transmitter release. This model predicts that pharmacological block of gap
      junctions should reduce the Ca2+ current at the equivalent cone voltage, thereby
      decreasing the postsynaptic light response. To test this prediction, and estimate
      the relative magnitude of this effect on third-order cells, we recorded light
      responses in mouse ganglion cells under photopic conditions and applied two gap
      junction antagonists, carbenoxolone and the structurally related 18beta
      glycyrrhetinic acid (GA). Both carbenoxolone and GA decreased the size of the
      light response to about 30% of control. Cells that were physiologically
      identified as ON, OFF, or ON/OFF were equally affected by carbenoxolone/GA. These
      gap junction blockers did not interfere with gamma-aminobutyric acid (GABA) or
      glutamate receptors, as they did not affect responses to direct activation of
      these receptors. Under control conditions, spots larger than 200 microm in
      diameter activated ganglion cell receptive-field surrounds. Comparing responses
      to small and large spots before and during carbenoxolone treatment, we found that
      carbenoxolone did not preferentially inhibit surround antagonism at the ganglion
      cell level, but instead scaled the responses to all spot sizes. Our results
      extend the findings of studies in lower vertebrates which showed that light
      responses in horizontal cells are decreased by carbenoxolone treatment, and
      support the idea that hemichannels in the outer retina, most likely on horizontal
      cells, constitute important gates that are critical for allowing light responses
      to move forward into the retinal circuit. Furthermore, it suggests that ganglion
      cell surrounds are generated in the inner retina.

PMID- 14658772
TI  - Light adaptation and color opponency of horizontal cells in the turtle retina.
AB  - Chromaticity-type (C-type) horizontal cells of the turtle retina receive
      antagonistic inputs from cones of different spectral types, and therefore their
      response to background illumination is expected to reflect light adaptation of
      the cones and the interactions between their antagonistic inputs. Our goal was to
      study the behavior of C-type horizontal cells during background illumination and
      to evaluate the role of wavelength in background adaptation. The photoresponses
      of C-type horizontal cells were recorded intracellularly in the everted eyecup
      preparation of the turtle Mauremys caspica during chromatic background
      illuminations. The voltage range of operation was either reduced or augmented,
      depending upon the wavelengths of the background and of the light stimuli, while
      the sensitivity to light was decreased by any background. The response-intensity
      curves were shifted to brighter intensities and became steeper as the background
      lights were made brighter regardless of wavelength. Comparing the effects of cone
      iso-luminant backgrounds on the Red/Green C-type horizontal cells indicated that
      background desensitization in these cells could not solely reflect background
      adaptation of cones but also depend upon response compression/expansion and
      changes in synaptic transmission. This leads to wavelength dependency of
      background adaptation in C-type horizontal cells, that is expressed as increased
      light sensitivity (smaller threshold elevation) and improved suprathreshold
      contrast detection when the wavelengths of the background and light stimuli were
      chosen to exert opponent effects on membrane potential.

PMID- 14658773
TI  - Immunolocalization of TRPC channel subunits 1 and 4 in the chicken retina.
AB  - In the vertebrate retina, multiple cell types express G protein-coupled receptors
      linked to the IP3 signaling pathway. The signaling engendered by activation of
      this pathway can involve activation of calcium permeable transient receptor
      potential (TRP) channels. To begin to understand the role of these channels in
      the retina, we undertake an immunocytochemical localization of two TRP channel
      subunits. Polyclonal antibodies raised against mammalian TRPC1 and TRPC4 are used
      to localize the expression of these proteins in sections of the adult chicken
      retina. Western blot analysis indicates that these antibodies recognize avian
      TRPC1 and TRPC4. TRPC1 labeling is almost completely confined to the inner
      plexiform layer (IPL) where it labels a subset of processes that ramify in three
      broad stripes. Occasionally, cell bodies are labeled. These can be found in the
      inner nuclear layer (INL) proximal to the IPL, the IPL, and the ganglion cell
      layer (GCL). Double-labeling experiments using a polyclonal antibody that
      recognizes brain nitric oxide synthase (bNOS) in the chicken indicate that many
      of the TRPC1-positive processes and cell bodies also express bNOS. Labeling with
      the TRPC4 antibody was much more widespread with some degree of labeling found in
      all layers of the retina. TRPC4 immunoreactivity was found in the photoreceptor
      layer, in the outer plexiform layer (OPL), in radially oriented cells in the INL,
      diffusely in the IPL, and in vertically oriented elements below the GCL. Double
      labeling experiments with a monoclonal antibody raised against vimentin indicate
      that the TRPC4-positive structures in the INL and below the GCL are Muller cells.
      Thus, TRPC1 and TRPC4 subunits have unique expression patterns in the adult
      chicken retina. The distributions of these two subunits indicate that different
      retinal cell types express TRP channels containing different subunits.

PMID- 14658774
TI  - Magnetic resonance: new approaches to imaging of the musculoskeletal system.
AB  - Recent technical advances in magnetic resonance imaging are reviewed. Purpose
      designed musculoskeletal magnetic resonance (MR) systems are now available. A
      great deal of pulse sequence development has been carried out with ultrashort TE
      (UTE) imaging, blood oxygenation level detection (BOLD) studies, diffusion
      weighted and other sequences. Image processing and measurement techniques have
      improved. In hyaline articular cartilage the deep layer can now be identified.
      Contrast agents are now being used to study the reduction in proteoglycans in
      cartilage. Enhancement is seen in tendons, ligaments and menisci and can be used
      to study perfusion. Signal is detected from cortical bone and periosteum and this
      can be used to monitor perfusion in serial studies. Muscle metabolism can also be
      studied. Contrast transport into intervertebral discs can be observed as well as
      effects attributable to iron deposition.

PMID- 14658775
TI  - A new index for the analysis of heart rate variability dynamics: characterization
      and application.
AB  - A new index for the analysis of the heart rate variability (HRV) dynamics is
      presented. The proposed index (acceleration change index (ACI)) characterizes the
      sign of the differences of a time series. A theoretical study shows an expression
      that relates ACI and the autocorrelation function of the time series. This
      formula is tested and validated with different simulated time series
      (uncorrelated noise, sinusoidal and fractional Brownian motion). Next, ACI is
      applied to RR time series from healthy subjects showing that ACI decreases with
      periodic controlled breathing, increases during exercise, and it has a lower
      value at night than during the day. In a preliminary study, ACI has been shown to
      be lower in healthy subjects than in patients who had suffered a myocardial
      infarction one month previously. ACI can be employed as a fast and robust new
      marker of the HRV dynamics.

PMID- 14658776
TI  - Vaginal algometer: development and application of a device to monitor vaginal
      wall pressure pain threshold.
AB  - We describe a device (which we have named a vaginal algometer) which can measure
      the pressure pain threshold (PPT) on the lateral walls of the vagina. The device
      was assessed in 63 healthy women and a normal range for this measurement was
      established. Each woman had her vaginal wall PPT measured and was asked about the
      acceptability of the procedure. We demonstrate that the vaginal algometer can
      provide a quantitative assessment of vaginal PPT and that the procedure is
      acceptable to most women.

PMID- 14658777
TI  - Analysis of intraluminal impedance measurements.
AB  - Intraluminal impedance is an emerging technique to monitor the esophagus so that
      the occurrence of gastroesophageal reflux episodes can be observed. The impedance
      traces of the esophagus have wide variations which correspond to the occurrence
      of activities such as swallow or reflux that cause the impedance to change. This
      paper presents a technique to detect and classify reflux episodes from
      intraluminal impedance. Evaluation of the technique based on 660 h of combined
      data from 30 patients showed that the proposed methodology can detect episodes in
      the esophagus to a sensitivity of 89% with positive predictivity of 83%.

PMID- 14658778
TI  - Determining the relationship of heart rate and blood pressure using voluntary
      cardio-respiratory synchronization (VCRS).
AB  - Voluntary cardio-respiratory synchronization (VCRS) was used to investigate heart
      rate and blood pressure changes in the supine position in 21 subjects. VCRS
      involves a breathing pattern that is synchronized with the cardiac cycle. The
      signals to inhale and exhale are derived from the ECG. In this study, the
      subjects inspired for four heart beats and expired for four heart beats for 35
      cycles. This technique is designed to have the heart beat occur at exactly the
      same phase in the respiratory cycle and lends itself to the study of the
      influence of the respiration cycle on heart rate and blood pressure changes. The
      heart rate and blood pressure changed simultaneously in the same direction, with
      the largest significant positive change occurring on the second heart beat during
      inspiration. The authors discuss the potential of VCRS for research, and clinical
      applications as a respiration modulator for hypertension therapy or increased
      heart rate variability.

PMID- 14658779
TI  - Polymyositis--a further investigation.
AB  - In essence, this paper describes the model-based interpretation of measurements
      in order to gain insight into physiological processes. The paper extends the
      mathematical model developed previously to control and monitor a polymyositis
      patient. The extension considers two further yet different types of muscle
      attack. The model is applied to simulate, first, the total serum creatine kinase
      levels, which then are matched to the observed values. The outcomes of this
      approach yield considerable information about the reactions taking place
      including various concentration levels over time such as prednisolone. The
      changes in the muscle attack are estimated. Examples illustrate how the model may
      be used to assess, for a single patient, the maximum reduction of the muscle
      attack whilst keeping the prednisolone concentration as low as possible. The
      model has been successfully used to interpret variations in daily heart rate
      measurements of a polymyositis patient. Consequently, it is shown how daily heart
      rate measurements may now be used to complement the control and monitoring of the
      polymyositis patient. The model is used to explore multi-patient statistics. It
      shows the dangers of using such an approach. The model illustrates the need for
      longitudinal studies.

PMID- 14658780
TI  - A pH-mucosa area unit of measure to consider morphology of the oesophagus when
      evaluating oesophagitis.
AB  - Gastro-oesophageal pH measurements are routinely carried out to quantify and
      determine if levels of acid reflux are responsible for symptoms. Although
      considered the 'gold standard', evidence suggests that pH measurements do not
      correlate well with the degree of oesophagitis seen during endoscopy. In this
      study the current measure of pH was critically examined taking into account both
      the effects of changes in luminal diameter and endoscopy observations. The
      oesophageal lumen diameter was investigated using a barium swallow for 25
      patients presenting with oesophageal disorders. For each subject the widest
      luminal diameter was measured for a series of five controlled swallows. The
      results showed that the lumen diameter varied widely from 0.9 to 3.8 cm. An
      alternative approach to the current measurement of pH was explored. In this
      approach the exposure not only included the luminal pH and time exposed but also
      the area of mucosa exposed as a result of differing luminal diameters. Although
      it is currently not possible to assess the diameter or morphology of the
      oesophageal lumen during a pH study, the analysis highlighted that the current
      measure of pH exposure time does not include the area of mucosa exposed. These
      results may explain, to some extent, the poor correlation between pH measurements
      and degree of oesophagitis seen during endoscopy.

PMID- 14658781
TI  - A model of physical factors in the structural adaptation of microvascular
      networks in normotension and hypertension.
AB  - Adequate function of the microcirculation is vital to any tissue. To maintain an
      optimal function, microvascular networks must be able to adapt structurally to
      changes in the physical environment. Here we present a mathematical network model
      based on vessel wall mechanics. We assume based on experimental observations that
      longstanding change in transmural pressure elicits a change in the vascular wall
      to-lumen ratio for maintaining circumferential wall stress at a certain level. In
      addition, experimental observations show that chronic change in fluid shear
      stress at the vascular wall elicits a persistent change in luminal diameter. On
      this basis we hypothesize that wall influencing substances released from the
      endothelium in response to shear stress have a certain optimal level in the
      vascular wall. Deviation from this level will cause vascular remodeling, i.e. a
      structural change in luminal diameter, until equilibrium is restored. The model
      explains several of the key features observed experimentally in the
      microcirculation in normotension and hypertension. Most importantly, it suggests
      a scenario where overall network structure and network hemodynamics depend on
      adaptation to local hemodynamic stimuli in the individual vessel. Simulated
      results show emanating microvascular networks with properties similar to those
      observed in vivo. The model points to an altered endothelial function as a key
      factor in the development of vascular changes characteristic of hypertension.

PMID- 14658782
TI  - Comparison of R-wave detection errors of four wireless heart rate belts in the
      presence of noise.
AB  - Four commercial wireless chest belts (Vetta, Nashbar, Polar and new Polar) were
      assessed for their susceptibility to noises in R-wave detection. A normal ECG
      signal was generated using a LionHeart simulator (Bio-tek Instruments, Inc.) with
      a fixed RR interval (750 ms) and R-wave amplitude (1 mV). Different levels of EMG
      and baseline wanderings (sinusoidal waves) were recorded from a healthy subject
      and a Quartec Model MFG-1 generator, respectively. They were added to the ECG
      signal in a BioPac system (BioPac systems Inc., Santa Barbara, CA) to simulate an
      ECG in physiological noise. The BioPac system applied the 'contaminated' ECG to
      the belts via a voltage divider. A PC-based Polar Precision Performance system
      was used to receive the detected R-wave pulses transmitted from the wireless
      belts and to calculate the RR intervals. Two types of detection errors were
      observed in the RR intervals: small time shifts, the potentially non-fixable
      small variance, and missed/false beats, the abnormally large and potentially
      fixable intervals. Results showed that small time shifts exist in all tests
      ranging from -10 ms to 10 ms and increase with the level of EMG before
      missed/false beats occur. Missed/false beats occur only when EMG level is beyond
      the threshold of 0.4 mV, 1.6 mV, 1.2 mV and 1.2 mV for Vetta, Nashbar, Polar and
      new Polar, respectively. The potential to detect and fix EMG introduced
      missed/false beats showed that this type of error could only be improved when the
      added EMG was below a certain value. Results also showed that no missed/false
      beats occur when the frequency and amplitude of sinusoidal waves were below 1 Hz
      and 5 mV.

PMID- 14658783
TI  - Macrocirculation is not the sole determinant of respiratory induced variations in
      the reflection mode photoplethysmographic signal.
AB  - Photoplethysmography (PPG) is a non-invasive optical technique sensitive to
      variations in blood volume and perfusion in the tissue. Reflection mode PPG may
      have clinical advantages over transmission mode PPG. To improve clinical
      usefulness and further development of the reflection mode PPG, studies on factors
      that modify the signal are warranted. We studied the coherence between the
      respiratory induced intensity variations (RIIV) of the PPG signal and respiratory
      synchronous pressure variations in central venous pressure (CVP), peripheral
      venous pressure (PVP) and arterial blood pressure (ABP) during positive pressure
      ventilation on 12 patients under anaesthesia and on 12 patients with spontaneous
      breathing. During positive pressure ventilation the coherence between all signals
      was high. Inspiration was followed first by an increase in CVP, then by increases
      in ABP and PVP and lastly by RIIV indicating less back-scattered light. In
      spontaneously breathing patients the coherence was high, but the phases between
      the signals were changed. During inspiration, ABP decreased slightly before CVP,
      followed by a decrease in RIIV and PVP. The phase relation between RIIV and
      respiratory induced variation in macrocirculation changed with ventilatory mode,
      but not in a uniform way, indicating the influence of mechanisms other than
      macrocirculation involved in generating the RIIV signal.

PMID- 14658784
TI  - Individual variations in mucosa and total wall thickness in the stomach and
      rectum assessed via endoscopic ultrasound.
AB  - Endoscopic ultrasound is a unique tool to acquire in vivo data on alimentary
      tract wall thicknesses of sufficient resolution needed in radiation dosimetry
      studies. Through their different echo texture and intensity, five layers of
      differing echo patterns for superficial mucosa, deep mucosa, submucosa,
      muscularis externa and serosa/adventitia exist within the walls of organs
      composing the alimentary tract. In this study, retrospective image analyses of
      patient video data were made for ten examinations of the stomach and eight
      examinations of the rectum covering a range of patient ages. Thicknesses for
      stomach mucosa ranged from 1030 +/- 130 microm to 1640 +/- 80 microm (total
      stomach wall thicknesses from 2.80 +/- 0.12 to 4.23 +/- 0.03 mm). Measurements
      made for the rectal images revealed rectal mucosal thicknesses from 660 +/- 50
      microm to 1130 +/- 250 microm (total rectal wall thicknesses from 2.28 +/- 0.05
      to 3.55 +/- 0.43 mm). The mucosa accounted for approximately 32 +/- 7% and
      approximately 32 +/- 8% of the total thickness of the stomach and rectal wall,
      respectively. These values can thus be utilized to investigate uncertainties in
      alimentary tract dosimetry that are based upon fixed reference individual
      definitions of organ wall structure.

PMID- 14658785
TI  - Morphometric and biomechanical remodelling following reopening of the obstructed
      bile duct.
AB  - Obstruction in the common bile duct results in duct dilatation, increased wall
      thickness and stiffening of the wall. Whether these changes are reversible after
      release of the obstruction has not yet been studied in detail. The aim of this
      study was to create a porcine model for release of bile duct obstruction and to
      describe biomechanical and morphometric parameters in a time-dependent design
      after the reopening. The bile duct of pigs was completely obstructed for one week
      and then reopened. Eighteen animals were allocated into four groups: unobstructed
      (group 1, n = 5), one week of obstruction (group 2, n = 5) and one week of
      obstruction followed by release of the obstruction after one week (group 3, n =
      4), and four weeks (group 4, n = 4), respectively. The bile ducts were examined
      in vitro on the day of termination. One week of obstruction induced pronounced
      dilatation and wall thickening. Both the diameter and wall thickness decreased
      after release of the obstruction (p < 0.05) but without reaching the unobstructed
      level. The biomechanical properties in terms of the circumferential stress-strain
      relation differed between groups (p < 0.01). Groups 3 and 4 were transposed to
      the left of the other groups, indicating that they had the stiffest wall. The
      wall was stiffer in the longitudinal direction when compared to the
      circumferential direction in all groups (p < 0.05). The collagen amount decreased
      after releasing the obstruction (p < 0.01). The collagen amount correlated to the
      wall thickness (r > 0.9 and p < 0.001) and wall thickness-to-radius ratio (r >
      0.7 and p < 0.05) in each of the two groups with release of the obstruction.

PMID- 14658786
TI  - Monitoring cerebral perfusion using near-infrared spectroscopy and laser Doppler
      flowmetry.
AB  - This paper describes the simultaneous use of two, noninvasive, near-infrared
      techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser
      Doppler flow system (LDF) to measure changes in the blood oxygenation, blood
      concentration and blood flow velocity in the brain. A piglet was used as animal
      model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for
      achieving changes in the listed cerebrovascular parameters. The time courses of
      blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were
      found to correspond closely with those of carotid blood flow and arterial carbon
      dioxide pressure (PaCO2). This result shows the additional value of LDF when
      combined with NIRS, preferably in one instrument. Development of pulsed LDF for
      regional blood flow measurement is indicated.

PMID- 14658787
TI  - The peptaibol database: a sequence and structure resource.
AB  - The peptaibols are a large family of membrane-active peptides with considerable
      sequence homology, but with different biological properties and three-dimensional
      structures. They constitute a rich resource of naturally occurring 'mutants'
      which are potentially valuable for structure/function studies of ion channels. A
      searchable on-line database of sequences and structures of the peptaibols has
      been created at http://www.cryst.bbk.ac.uk/peptaibol, as a resource for the
      biological and structural community. In this paper, the contents and organization
      of the website are discussed as well as procedures for submission of new entries
      to the database. At present, more than 300 peptaibol sequences are stored in the
      database. Each sequence entry contains its full literature reference and
      information about its biological source. Tools are provided for searching for
      specific peptaibol sequences or groupings of sequences, and for locating
      peptaibols containing specified sequence motifs. In addition the website acts as
      a database for structural information. The coordinates of all currently available
      peptaibol x-ray and NMR structures are included and complemented, where
      appropriate. with molecular graphics illustrations. These include figures of
      model channel structures and comparisons between different peptaibol structures.
      The peptaibol database thus provides a tool for ready access to information and a
      means of investigating the sequences and structures of this class of
      polypeptides.

PMID- 14658788
TI  - The occurrence of peptaibols and structurally related peptaibiotics in fungi and
      their mass spectrometric identification via diagnostic fragment ions.
AB  - Peptaibols and related peptide antibiotics (peptaibiotics) display diagnostically
      useful fragmentation patterns during mass spectrometry (FAB-MS, ESI-CID-MS/MS and
      CID-MSn]. The paper compiles fragmentation data of pseudo-molecular ions reported
      in the literature as a guide to the rational identification of recurrently
      isolated and new peptaibols and peptaibiotics. Taxonomic and ecological aspects
      of microorganisms producing peptaibols and peptaibiotics are discussed.

PMID- 14658789
TI  - Trichogin: a paradigm for lipopeptaibols.
AB  - Lipopeptaibols are members of a novel family of naturally occurring, short
      peptides with antimicrobial activity, characterized by a lipophilic acyl chain at
      the N-terminus, a high content of turn/helix inducing alpha-aminoisobutyric acid
      and a 1,2-amino alcohol at the C-terminus. Using solution methods, the
      prototypical lipopeptaibol trichogin GA IV and a large series of appropriately
      designed analogues were synthesized, which allow: (i) determination of the
      minimal lipid chain and peptide main-chain lengths for the onset of membrane
      activity, and (ii) exploitation of a number of physico-chemical techniques aimed
      at assessing the trichogin preferred conformation under a variety of conditions
      and at investigating its mechanism of interaction with the phospholipid
      membranes.

PMID- 14658790
TI  - A nonribosomal peptide synthetase involved in the biosynthesis of ampullosporins
      in Sepedonium ampullosporum.
AB  - Recently, the saprophytic ascomycete Sepedonium ampullosporum strain HKI-0053 was
      isolated from a basidiomycete on account of its premature induction of pigment
      formation in Phoma destructiva, a process often related to the neuroleptic
      activity of the inducing compound. The active substance was identified as the 15
      membered peptaibol type peptide Ampullosporin. Although to date more than 300
      peptaibols have been discovered, their biosynthetic machinery has not been
      characterized yet. By improving the culture conditions it was possible to grow S.
      ampullosporum in a submerged culture and to increase Ampullosporin production by
      more than three times to 33 mg/l at reduced fermentation times. The appearance of
      two high molecular weight proteins, HMWP1 (1.5 MDa) and HMWP2 (350 kDa) was
      closely related to the production of Ampullosporin during the course of
      fermentation. Both proteins showed a cross-reaction with antibodies against a
      core fragment of nonribosomal peptide synthetases (NRPSs). Biochemical
      characterization of the partially purified enzymes exhibited selectivity for the
      substrate amino acid alpha-aminoisobutyric acid (Aib). substantiating their
      involvement in Ampullosporin biosynthesis. Our data suggest that Ampullosporin
      synthetase has been isolated, and provides the basis for the characterization of
      the entire biosynthetic gene cluster. Furthermore, this knowledge will enable the
      manipulation of its NRPS template, in order to engineer mutant strains of
      Sepedonium ampullosporum which could produce more potent analogues of
      Ampullosporin.

PMID- 14658791
TI  - Circular dichroism studies of ampullosporin-A analogues.
AB  - Ampullosporin A (AmpA), a 15mer peptalbol containing seven Aib residues is able
      to induce pigmentation on Phoma destructiva and hypothermia in mice, as well as
      to exhibit a neuroleptic effect. A circular dichroism study of ampullosporin A
      and its analogues was carried out in organic solvents with different polarities
      and detergent micelles to determine the relationship between their conformational
      flexibility and biological activities. The analogues were obtained by modifying
      the N- and C-termini of ampullosporin A. Furthermore, Gln and Leu were
      systematically substituted by Ala and Aib residues were replaced by Ala and/or
      Ac6c. To estimate the helicity of the analogues, the CD spectrum of AmpA recorded
      in acetonitrile was correlated to its crystal structure. All analogues displayed
      similar CD curve shapes in organic solvents with the ratio between two negative
      band intensities R = [theta]n-pi*/[theta]pi-pi* < 1. In acetonitrile, most of the
      analogues adopted a 70%-85% helical structure, which was higher than the average
      of 40%-60% obtained in TFE. In detergent micelles, the analogues were
      distinguishable by their CD profiles. For most of the biologically active
      analogues, the CD spectra in detergent micelles were characterized by a R ratio >
      1 and increased helicity compared with those recorded in TFE, suggesting that the
      interaction of the peptides with the membrane and peptide association was
      necessary for their hypothermic effect.

PMID- 14658792
TI  - Crystal structure and conformational analysis of ampullosporin A.
AB  - Ampullosporin A is a 15-mer peptaibol type polypeptide that induces pigment
      formation by the fungus Phoma destructiva, forms voltage-dependent ion channels
      in membranes and exhibits hypothermic effects in mice. The structure of
      ampullosporin A has been determined by x-ray crystallography. This is the first
      three-dimensional (3D) structure of the peptaibol subfamily SF6. From the N
      terminus to residue 13 the molecule adopts an approximate right-handed alpha
      helical geometry, whereas a less regular structure pattern with beta-turn
      characteristics is found in the C-terminus. Even though ampullosporin A does not
      contain a single proline or hydroxyproline it is significantly bent. It belongs
      to both the shortest and the most strongly bent peptaibol 3D structures. The
      straight structure part encompasses residues Ac-Trp(1)-Aib(10) and is thus less
      extended than the alpha-helical subunit. The 3D structure of ampullosporin A is
      discussed in relation to other experimentally determined peptaibol structures and
      in the context of its channel-forming properties. As a part of this comparison a
      novel bending analysis based on a 3D curvilinear axis describing the global
      structural characteristics has been proposed and applied to all 3D peptaibol
      structures. A sampling of 2500 conformations using different molecular dynamics
      protocols yields, for the complete ampullosporin A structure, an alpha-helix as
      the preferred conformation in vacuo with almost no bend. This indicates that
      solvent or crystal effects may be important for the experimentally observed
      peptide backbone bending characteristics of ampullosporin A.

PMID- 14658793
TI  - Crystal structures of cephaibols.
AB  - The crystal structures of the peptaibol antibiotics cephaibol A, cephaibol B and
      cephaibol C have been determined at ca. 0.9 A resolution. All three adopt a
      helical conformation with a sharp bend (of about 55 degrees) at the central
      hydroxyproline. All isovalines were found to possess the D configuration,
      superposition of all four models (there are two independent molecules in the
      cephaibol B structure) shows that the N-terminal helix is rigid and the C
      terminus is flexible. There are differences in the hydrogen bonding patterns for
      the three structures that crystallize in different space groups despite
      relatively similar unit cell dimensions, but only in the case of cephaibol C does
      the packing emulate the formation of a membrane channel believed to be important
      for their biological function.

PMID- 14658794
TI  - Three complete turns of a 3(10)-helix at atomic resolution: the crystal structure
      of Z-(Aib)11-OtBu.
AB  - The crystal structure of the synthetic protected oligopeptide Z-(Aib)11-OtBu was
      determined by x-ray crystallography. The undecapeptide folds in a regular 3(10)
      helix with nine consecutive 4 --> 1 hydrogen bonds. At present, this is the
      largest available structure of a homopeptide (including homopeptides consisting
      of standard amino acids) and also the longest observed regular 3(10)-helix at
      atomic resolution. Z-(Aib)11-OtBu crystallizes readily from hot ethanol-water
      mixture and is one of the crystals in which no solvent molecule is co
      crystallized. In the crystal head-to-tail hydrogen bonded columns are formed in
      the [1 0 1] direction. Each helical column is surrounded by six others, whereby
      two are packed in parallel and four in antiparallel fashion. Helical columns are
      packed via apolar crystal contacts. The crystal structure of Z-(Aib)11-OtBu is
      compared with the crystal structures of Z-(Aib)10-OtBu and Z-(Aib)9-OtBu. The
      similarities and differences are analysed.

PMID- 14658795
TI  - Differences in membrane pore formation by peptaibols.
AB  - The efficiencies of membrane pore formation by 14 naturally occurring peptaibols
      and two structurally modified ampullosporins were compared using an artificial
      bilayer membrane model. Major differences were found in the dependence on peptide
      sequences and the constituting amino acids. Alamethicin F-30, chrysospermins C/D,
      paracelsin and texenomycin A displayed higher activity by several orders of
      magnitude in comparison with smaller peptaibols containing < 17 amino acids such
      as ampullosporins, trichofumins. bergofungins and cephaibols. Biological
      activities such as the induction of pigment formation by the fungus Phoma
      destructiva and long acting hypothermia and depression of locomotor activity in
      mice were correlated with moderate membrane permeabilization. No or weak membrane
      activities corresponded with biological inactivity. Highly membrane-active
      structures such as alamethicin F-30, chrysospermin C, texenomycin A and
      paracelsin A displayed antibiotic effects against the fungus and toxicity in
      mice.

PMID- 14658796
TI  - The peptaibol antiamoebin as a model ion channel: similarities to bacterial
      potassium channels.
AB  - Antiamoebin (AAM) is a polypeptide antibiotic that is capable of forming ion
      channels in phospholipid membranes: planar bilayer studies have suggested the
      channels are octamers. The crystal structure of a monomeric form of AAM has
      provided the basis for molecular modelling of an octameric helical bundle
      channel. The channel model is funnel-shaped due to a substantial bend in the
      middle of the polypeptide chain caused by the presence of several imino acids.
      Inter-monomer hydrogen bonds orientate a ring of glutamine side chains to form a
      constriction in the pore lumen. The channel lumen is lined both by side chains of
      Gln11 and by polypeptide backbone carbonyl groups. Electrostatic calculations on
      the model are compatible with a channel that transports cations across membranes.
      The AAM channel model is compared with the crystal structures of two bacterial
      (KcsA andMthK) potassium channels. AAM and the potassium channels exhibit common
      functional features, such as cation-selectivity and similar single channel
      conductances. Common structural features include being multimers, each formed
      from a bundle of eight transmembrane helices, with lengths roughly comparable to
      the thickness of lipid bilayers. In addition, they all have aromatic amino acids
      that lie at the bilayer interfaces and which may aid in the stabilization of the
      transmembrane helices, as well as narrower constrictions that define the ion
      binding sites or selectivity filters in the pore lumen. The commonality of
      structural and functional features in these channels thus suggests that
      antiamoebin is a good, simple model for more complex bacterial and eukaryotic ion
      channels, capable of providing insight into details of the mechanisms of ion
      transport and multimeric channel stability.

PMID- 14658797
TI  - Channel properties of template assembled alamethicin tetramers.
AB  - The multiple conductance levels displayed by the antibiotic alamethicin in planar
      lipid bilayers is explained by a dynamic 'barrel-stave' model, the conducting
      pore resulting from the aggregation of up to ten helical amphipathic helical
      monomers. However, the precise assignment of an oligomerization state to a
      particular single-channel conductance substate is far from being experimentally
      clear. In addition, it could be useful to tailor a given channel geometry to
      selectively allow the permeation of solutes with different molecular sizes,
      whilst retaining a high voltage-dependence. To control the aggregation state of
      the channel, the TASP (template assembled synthetic proteins) strategy was
      applied to synthesize structurally defined oligomers, i.e. dimer, trimer,
      tetramer. The modulation of conductance properties of three alamethicin tetramers
      with the length and flexibility of the linkers of the 'open' or linear template
      is described. It is shown that the introduction of an alanine between the
      contiguous lysines to which are tethered C-terminally modified alamethicin
      helical monomers stabilizes the open channel states, whereas the alanine
      substitution by Pro-Gly, a reverse beta-turn promoting motif, increases voltage
      dependence and leads to single-channel conductance values more in line with the
      expected ones from a tetrameric bundle.

PMID- 14658798
TI  - Template-free self-assembling fullerene and lipopeptide conjugates of alamethicin
      form voltage-dependent ion channels of remarkable stability and activity.
AB  - N- and C-terminally modified with fullerene or lipopeptide alamethicin molecules
      were designed for the formation of template-free, self-assembling, voltage
      dependent ion conducting channels. The automated solid phase synthesis of the
      alamethicin-F30 sequence was performed by in situ fluoride activation on 2
      chlorotritylchloride-polystyrene resin and the conjugation with fullerenes-C60
      and -C70 was carried out in solution. Voltage-dependent bilayer experiments
      revealed preferred channel sizes for C-terminal alamethicin F30-fullerene-C60 and
      -C70 conjugates and higher activity compared with native alamethicin, whereas N
      terminally linked fullerene balls destabilize pore formation. C-terminal
      alamethicin F30-fullerene-C70 conjugates show pore states with remarkably long
      lifetimes of seconds. C-terminal lipopeptide conjugates of alamethicin were
      prepared by coupling via short peptide spacers with synthetic tripalmitoyl-S
      glyceryl-cysteine. which represents the strong membrane anchoring N-terminus of
      bacterial lipoprotein. Alamethicin-lipopeptide conjugates exhibit high channel
      forming activities, whereby they self-assemble and adopt preferred pore states
      with extremely long lifetimes. The novel membrane modifying peptaibol constructs
      are valuable lead compounds for developments in sensorics related to
      transmembrane ion conductance.

PMID- 14658799
TI  - Sequences of alamethicins F30 and F50 reconsidered and reconciled.
AB  - From the culture broth of the mould Trichoderma viride, strain NRRL 3199, a
      microheterogeneous mixture of the membrane active 20-residue peptaibol
      alamethicin (ALM) could be isolated. ALMs were isolated by XAD-2 column
      chromatography and separated by silica gel chromatography and
      trichloromethane/MeOH gradient elution into an acidic and neutral group of
      peptides, named ALM F30 and ALM F50, respectively, according to their 100 Rf on
      TLC. Peptides ALM F50 were separated by semi-preparative and analytical HPLC and
      subjected to ESI-MS. Ten sequences of ALM F30 and their relative quantities could
      be determined. The major peptides ALM F30/3 (46%) and ALM F30/7 (40%),
      distinguished by Aib/Ala exchange in position 6, correspond to sequences
      described as ALM I and II occurring in the original alamethicin from Upjohn
      Company. Analogously, 13 sequences of the neutral peptide mixture named ALM F50
      could be determined. The major peptide ALM F50/5 (75%) and the minor peptide ALM
      F50/7 (10%) are distinguished from ALM F30/3 and ALM F30/7 by having Gln17 in
      place of Glu17, the latter occurring in the F30 group. Notably. currently
      commercially available alamethicins (Fluka, Sigma) represent microheterogeneous
      mixtures of the neutral ALM F50 peptides with trace amounts of acidic ALM F30
      peptides.

PMID- 14658800
TI  - Isolation, structure elucidation and biological activities of trichofumins A, B,
      C and D, new 11 and 13mer peptaibols from Trichoderma sp. HKI 0276W.
AB  - Trichofumins A-D were isolated from cultures of Trichoderma sp. HKI 0276 as new
      11 and 13mer peptaibols. Similar to 15mer peptaibols they promote morphogenesis
      of the fungus Phoma destructiva and cause hypothermia in mice as a characteristic
      of neuroleptic activity. Membrane measurements using a synthetic BLM model showed
      that A, B, C and D increased membrane permeability for cations in a similar
      manner as was shown for larger peptaibols but with comparably lower efficiency.

PMID- 14658801
TI  - Biosynthetic uniform 13C,15N-labelling of zervamicin IIB. Complete 13C and 15N
      NMR assignment.
AB  - Zervamicin IIB is a member of the alpha-aminoisobutyric acid containing peptaibol
      antibiotics. A new procedure for the biosynthetic preparation of the uniformly
      13C- and 15N-enriched peptaibol is described This compound was isolated from the
      biomass of the fungus-producer Emericellopsis salmosynnemata strain 336 IMI 58330
      obtained upon cultivation in the totally 13C, 15N-labelled complete medium. To
      prepare such a medium the autolysed biomass and the exopolysaccharides of the
      obligate methylotrophic bacterium Methylobacillus flagellatus KT were used. This
      microorganism was grown in totally 13C, 15N-labelled minimal medium containing
      13C-methanol and 15N-ammonium chloride as the only carbon and nitrogen sources.
      Preliminary NMR spectroscopic analysis indicated a high extent of isotope
      incorporation (> 90%) and led to the complete 13C- and 15N-NMR assignment
      including the stereospecific assignment of Aib residues methyl groups. The
      observed pattern of the structurally important secondary chemical shifts of
      1H(alpha), 13C=O and 13C(alpha) agrees well with the previously determined
      structure of zervamicin IIB in methanol solution.

PMID- 14658802
TI  - Synthesis of the protected 6-16 segment of zervamicin 11-2, an application of the
      azirine/oxazolone method.
AB  - The protected 11 amino acid segment (6-16) of the peptaibol zervamicin II-2 was
      synthesized by using the 'azirine/oxazolone method' for the introduction of all
      Aib residues. Whereas a 2,2-dimethyl-2H-azirin-3-amine was used as the building
      block for Aib(7), methyl 2,2-dimethyl-2H-azirine-3-prolinate and -3-(3
      hydroxyprolinate) proved to be ideally suited as dipeptide synthons for the
      introduction of Aib-Pro and Aib-Hyp, respectively. The coupling of Z-protected
      amino acids or peptide acids with the 2H-azirin-3-amines were performed in 75% to
      quantitative yield.

PMID- 14658803
TI  - Understanding the structure of the unicuspid and unicommissural aortic valve.

PMID- 14658804
TI  - Incidence and echocardiographic features of congenital unicuspid aortic valve in
      an adult population.
AB  - BACKGROUND AND AIM OF THE STUDY: Although well described in pediatric
      populations, series of congenital unicuspid aortic valves in adults are limited
      and mainly arise from surgical reports. Also, the incidence of this rare
      congenital anomaly has never been estimated in an adult echocardiographic
      population. METHODS: Between January 1990 and May 2002, the authors'
      echocardiographic database was systematically reviewed to identify adult patients
      with congenital unicuspid aortic valve. Echocardiographic studies were reviewed
      off-line to define morphologic characteristics and evaluate ascending aortic
      dimensions. RESULTS: Twenty-one adult patients with congenital unicuspid aortic
      valve were identified, resulting in an estimated incidence in the referral
      population of approximately 0.02%. Aortic stenosis was the predominant associated
      hemodynamic lesion; on average, this required surgical intervention during the
      third decade of life. All valves were unicommissural with a posteriorly
      positioned commissural attachment. Of particular clinical importance, coexisting
      ascending aortic dilatation was found in almost half of the cohort (48%), despite
      the younger patient age. CONCLUSION: Adult congenital unicuspid aortic valve is a
      rare cardiac anomaly, even in a large referral population. On average, patients
      will present for cardiac surgery in their third decade of life. Aortic dilatation
      in association with unicuspid aortic valves should be well recognized and
      routinely assessed in the initial evaluation and follow up of these patients.

PMID- 14658805
TI  - Aortic valve repair versus replacement in bicuspid aortic valve disease.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to compare the results of
      aortic valve repair and replacement with biological valves in adult patients with
      aortic insufficiency (AI) caused by congenital bicuspid aortic valve (BAV)
      METHODS: Forty-four patients who had aortic valve repair were matched for age and
      left ventricular function to 44 patients who had aortic valve replacement (AVR)
      with biological valves. Patients were followed annually using echocardiography.
      The mean follow up was 2.6 +/- 2.1 years for the repair group, and 3.5 +/- 2.1
      years for the replacement group. Follow up was complete. RESULTS: There was no
      operative or late death in either group. Early postoperative echocardiography
      showed trace or no AI in 35 patients and mild AI in nine who had repair, and
      trace or no AI in 38 patients and mild AI in five who had AVR. The mean peak
      systolic gradient was 16.2 +/- 7.6 mmHg for repair and 13.2 +/- 7.2 mmHg for AVR.
      Four patients who had valve repair and two who had AVR, needed repeat aortic
      valve surgery because of progressive AI or endocarditis. Freedom from reoperation
      at five years was 91 +/- 5% for repair and 94 +/- 6% for replacement (p = 0.2),
      while freedom from moderate or severe AI at five years was 79 +/- 8% for repair
      and 94 +/- 6% for replacement (p = 0.024). The peak systolic gradient at follow
      up was 11.7 +/- 6.8 mmHg after repair and 13.3 +/- 9.6 mmHg after AVR (p = 0.4).
      There were no thromboembolic complications in either group. CONCLUSION: Repair of
      BAV is feasible in certain patients with AI, but the hemodynamics and clinical
      outcomes do not appear to be superior to AVR with biological valves during the
      first five years of follow up.

PMID- 14658806
TI  - Angiotensin-converting enzyme polymorphisms and their potential impact on left
      ventricular myocardial geometry after aortic valve surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: Genetic variants of the angiotensin-converting
      enzyme (ACE) cascade may influence left ventricular myocardial mass (LVMM)
      regression after aortic valve surgery. Postoperative long-term changes in LV
      indices were investigated in patients with asymptomatic aortic regurgitation (AR)
      and symptomatic aortic stenosis (AS) and related to alleles of ACE polymorphisms.
      METHODS: A total of 96 patients was included in the study, 21 with class IIa AR
      (22%) and 75 with class I AS (78%) recommendations for surgery. Patients were
      evaluated for demographic risk factors and underwent a thorough clinical
      examination including 3-D cardiac imaging by ultrafast-computed tomography.
      Genomic DNA was isolated for genotyping. RESULTS: AR patients were younger (55.8
      +/- 8.9 versus 64 +/- 9.1 years, p = 0.0014), had a larger body surface area
      (1.92 +/- 0.21 versus 1.82 +/- 0.19 m2, p = 0.039), and were more likely to be
      asymptomatic (myocardial infarction, p = 0.04; syncope, p = 0.0099;
      thromboembolism, p = 0.03; NYHA class IV, p = 0.04). Postoperatively, the
      reduction in absolute LVMM (from 297.1 +/- 52.6 to 190.1 +/- 57.1 g versus 214.4
      +/- 55.7 to 143.8 +/- 40.0 g; pT = 0.0000001) and indexed LVMM (from 156.0 +/-
      31.7 to 99.3 +/- 28.4 g/m2 versus 118.7 +/- 28.3 to 79.3 +/- 20.6 g/m; pT =
      0.0000001) over time was more significant in AR patients, but never reached
      normal values. Enforced ACE inhibitor medication resulted in significantly higher
      postoperative indexed LVMM differences in homozygote DD patients compared to AR
      patients with II/ID alleles of ACE 16 ins/del polymorphism. CONCLUSION: AR
      patients showed a statistically significant decrease in absolute/indexed LVMM
      during follow up, but never achieved LV mass recovery compared to standard values
      or to values in patients undergoing aortic valve replacement for AS. The benefits
      of ACE inhibitors were observed among AR patients with homozygote DD alleles of
      ACE 16 ins/del polymorphism.

PMID- 14658807
TI  - Transient dynamic mid-left ventricular obstruction following aortic valve
      replacement.
AB  - The case is presented of dynamic left ventricular mid-cavitary obstruction that
      complicated the postoperative course following aortic valve replacement and
      coronary artery bypass grafting. The condition resolved with appropriate medical
      management, without further surgical intervention. It is hypothesized that this
      was due to both concentric left ventricular hypertrophy and direct diastolic
      ventricular interaction.

PMID- 14658808
TI  - Morbidity and mortality of a failed attempt at mitral valve repair converted to
      replacement at the same operation.
AB  - BACKGROUND AND AIM OF THE STUDY: Although mitral valve repair (MVRpr) is the
      preferred operation for mitral disease worldwide, some surgeons are reluctant to
      attempt this, believing that excess morbidity and mortality will result if the
      attempt fails and conversion to mitral valve replacement (MVR) is necessary
      during surgery. METHODS: Typical preoperative, operative and postoperative
      parameters were reviewed retrospectively on 2,017 consecutive adults undergoing
      mitral valve operations (MVO), with and without additional cardiac surgery,
      between 1986 and 1999. Morbidity and mortality were compared for all MVRpr, MVR
      and attempted repairs, which failed and were converted to replacement at the same
      operation (FRpr). RESULTS: Although cross-clamp and extracorporeal pump times
      were longer for FRpr than for MVRpr and MVR, neither blood product use,
      morbidity, nor length of ICU or hospital stay was increased. Perioperative
      myocardial infarction was higher in FRpr, but less than 5%. Although operative
      mortality was lower for successful MVRpr compared with MVR, there was no
      difference between FRpr and either MVRpr or MVR, whether as an isolated or
      combined procedure. The addition of other cardiac procedures to a specific MVO
      appeared to be the important variable in mortality in all the groups, rather than
      the length of cross-clamp or extracorporeal pump times. CONCLUSION: An attempted
      MVRpr which fails and is converted to replacement at the same operation does not
      appear to be associated with excess morbidity or mortality, despite longer cross
      clamp and pump times. Accordingly, MVRpr can be safely undertaken when indicated,
      even with additional cardiac procedures.

PMID- 14658809
TI  - Percutaneous mitral balloon valvuloplasty in rheumatic mitral stenosis without
      heparin.
AB  - BACKGROUND AND AIM OF THE STUDY: Customarily, heparin is used to prevent embolic
      complications arising during percutaneous mitral balloon valvuloplasty (PMBV),
      but this may prolong hospital stay and increases the risk of bleeding,
      hemopericardium and cardiac tamponade. The study aim was to assess in-hospital
      complications of PMBV performed without heparin. METHODS: Rheumatic mitral
      stenosis patients undergoing PMBV between February 1997 and March 2000, either
      with (18 males, 91 females; mean age 37.5 +/- 8.8 years) or without (15 males,
      119 females; mean age 37.5 +/- 15.1 years) heparin at conventional doses, were
      included in the study. Neurologic and cardiac examinations were conducted after
      PMBV and repeated before discharge from hospital. RESULTS: There was no
      statistically significant difference between groups in terms of age, gender, NYHA
      class, presence of atrial fibrillation, spontaneous echo contrast, left atrial
      appendix thrombus, left atrial diameter and mitral valve echo score. There was no
      difference between groups with regard to procedural success, mitral valve area
      and gradient attained, or rates of mitral insufficiency. Ten patients in the
      heparin group required transesophageal echocardiography (TEE) guidance during
      PMBV (p <0.001). The mean duration of PMBV was greater in the heparin group due
      to increased use of TEE guidance during septal puncture. During follow up, no
      patients in the non-heparin group had hemopericardium, cardiac tamponade, embolic
      event or death; by comparison, in the heparin group one patient had
      hemopericardium and one had a cardiac tamponade. No major bleeding episode
      requiring transfusion occurred in either group, but six and 10 cases of minor
      bleeding at access sites occurred in the non-heparin and heparin groups,
      respectively (p = NS). Duration of hospitalization was statistically longer in
      the heparin group than in the non-heparin group. CONCLUSION: Avoidance of heparin
      did not lead to an increase in embolic complications. The vascular access sites
      were withdrawn early, thereby reducing the duration of hospital stay and time to
      ambulation. This method did not cause any increase in numbers of vascular
      complications and blood transfusions.

PMID- 14658810
TI  - Risk and benefit of sinus rhythm restoration by ablation techniques.

PMID- 14658811
TI  - Left atrial thrombosis following mitral valve repair and maze procedure: case
      report.
AB  - The case is described of a 71-year-old woman with left atrial thrombosis after
      successful mitral valve repair and a Kosakai-maze procedure. At three months
      after surgery, electrocardiography showed a normal sinus rhythm, but
      echocardiography revealed a mural thrombus on the posterior wall of the left
      atrium. During those three months, the anticoagulation level (thrombotest index
      range: 29-41%) was lower than target level. Anticoagulant therapy with heparin
      plus warfarin failed to reduce the thrombus size. Anticardiolipin antibodies were
      positive, and lupus anticoagulants negative. A Doppler study of the mitral valve
      indicated peak velocity 1.48 m/s, mean pressure gradient 4.5 mmHg, and valve area
      2.1 cm2. During reoperation, an old spherical thrombus (weight 38 g) which was
      firmly adhered to the posterior wall and included an incision line of the Kosakai
      maze procedure, was identified and totally removed. After reoperation, the
      patient received warfarin and an antiplatelet agent to maintain the INR at 2.5
      3.5. Echocardiography performed at 11 months postoperatively revealed no thrombus
      formation on the left atrium.

PMID- 14658812
TI  - Surgical management of mitral regurgitation in patients with Marfan syndrome.
AB  - BACKGROUND AND AIM OF THE STUDY: Although, in patients with Marfan syndrome, the
      most common cardiovascular abnormalities are aortic root dilatation and aortic
      valve regurgitation, mitral valve dysfunction is the most frequently accompanying
      cardiac lesion. METHODS: The clinical course and management is reported of nine
      patients (seven men, two women; mean age 29.2 +/- 2.3 years) with Marfan syndrome
      who required different mitral valve procedures and aortic valve replacement.
      Mitral regurgitation was caused by annulus dilatation in all patients, by leaflet
      prolapse in five patients, and by chordal rupture due to endocarditis in two. Six
      patients underwent mitral valve replacement; three of these were operated on
      using preservation of the mitral valve apparatus. Three patients underwent mitral
      annuloplasty and chordal shortening. RESULTS: There was no hospital mortality,
      nor any valve-related complications in the series. The postoperative course was
      uneventful after each operation. At a mean follow up of 4.5 years, all patients
      were in NYHA class I or II, with improved functional capacity. CONCLUSION: This
      experience in mitral valve procedures indicated that the connective tissue defect
      might compromise the results of such surgery, but that mitral valve operations
      could be performed satisfactorily in young Marfan syndrome patients, despite
      complications of left ventricular dilatation.

PMID- 14658813
TI  - Sclerosed lipoma of the mitral valve.
AB  - A very rare case of cardiac lipoma located in the mitral valve is presented.
      Clinical symptoms, diagnostic procedures, differential diagnosis and treatment
      are discussed, and the relevant literature briefly reviewed. The treatment of
      choice for these partially asymptomatic tumors is resection, and invasive
      diagnostic procedures such as transesophageal biopsy should be avoided. However,
      transesophageal echocardiography and magnetic resonance techniques are considered
      helpful in differentiating between benign and malignant tumors in order to plan
      effective surgery.

PMID- 14658814
TI  - The sinotubular junction does not progressively dilate four years after modified
      subcoronary freestyle stentless tissue aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic root dilation at the sinotubular junction
      (STJ) results in aortic regurgitation associated with normal valves and with a
      complete subcoronary stentless aortic bioprosthesis. The study aim was to assess
      for progressive aortic root dilation following modified subcoronary Freestyle
      aortic valve replacement (AVR), and to compare for differences between implant
      techniques. METHODS: Aortic root diameter was measured at the annulus, sinuses of
      Valsalva, STJ and tubular aorta on post-pump transesophageal echocardiograms and
      on early (3-month) and late (>2 years) transthoracic echocardiograms among 16
      patients after modified subcoronary Freestyle valve replacement, 16 after root
      inclusion, and three after total root replacement. RESULTS: Mean follow up was
      3.9 +/- 0.8, 3.3 +/- 0.7 and 3.5 +/- 1.1 years for modified subcoronary, root
      inclusion and total root patients, respectively. The aortic annulus, sinuses and
      STJ increased in diameter to similar extents between surgery and three months
      after modified subcoronary and root inclusion surgery, with no further increase
      at late follow up (modified subcoronary STJ 18.4 +/- 3.7, 21.1 +/- 3.7 and 20.5
      +/- 4.4 mm on intraoperative, early and late echocardiography, respectively; root
      inclusion STJ 21.8 +/- 3.9, 25.4 +/- 4.6 and 24.4 +/- 4.4 mm, respectively).
      There were no changes in aortic root diameter after total root replacement (STJ
      23.7 +/- 1.2 and 25.7 +/- 6.0 on intraoperative and late follow up,
      respectively). Aortic regurgitation prevalence was low, and similar between
      groups. CONCLUSION: Small but significant increases in aortic root dimensions
      were seen during the first three months after modified subcoronary and root
      inclusion surgery, with no subsequent change. The early changes were likely
      caused by resorption of paravalvular edema and hematoma transiently affecting
      aortic root measurements in the perioperative period. There was no evidence of
      progressive STJ dilation at 3.9 years after modified subcoronary Freestyle AVR.

PMID- 14658815
TI  - Evaluation of the decellularized pulmonary valve homograft (SynerGraft).
AB  - BACKGROUND AND AIM OF THE STUDY: Rejection is thought to contribute to the
      degeneration of valved homografts. A novel cryopreserved decellularized homograft
      valve (SynerGraft; CryoLife, Inc.) offers the unique opportunity to gain new
      insight into the immunology of homograft implantation and its significance for
      valve function. METHODS: Twenty-four patients (group I; mean age 37 +/- 11 years)
      underwent implantation of a pulmonary SynerGraft and were examined at one and six
      months postoperatively; 22 patients (group II; mean age 41 +/- 17 years) with
      conventional homografts served as controls. Temperature, C-reactive protein (CRP)
      levels and white blood cell count (WBC) were studied perioperatively. Follow up
      included echocardiography and anti-human leukocyte antigen (HLA) class I antibody
      determination. RESULTS: Significantly lower temperatures were measured in group I
      (p = 0.019). CRP level and WBC each increased postoperatively, but did not differ
      between groups. During follow up, none of the SynerGraft patients became positive
      for anti-HLA antibodies, compared with 66% of controls (p = 0.011). Homograft
      diameter and valve orifice area were decreased significantly at one month after
      surgery in groups I and II (25 +/- 1 versus 18 +/- 3 mm; 25 +/- 1 versus 19 +/- 2
      mm, respectively; p <0.001 both groups). Transvalvular pressure gradients
      significantly increased during follow up. CONCLUSION: Implantation of the
      SynerGraft pulmonary homograft appeared safe, and though evidence was found of a
      reduced immunologic response after SynerGraft implantation this (unexpectedly)
      did not translate into any hemodynamic advantage. Hence, factors other than
      rejection appear as the main contributions to the observed functional changes.

PMID- 14658816
TI  - Mineralization and organic phase modifications as contributory factors of
      accelerated degeneration in homograft aortic valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to assess histological and
      mineralogical properties of leaflets in human, antibiotic-preserved aortic
      homograft valves (recovered during surgical replacement) in order to identify
      factors accounting for pathological changes leading to accelerated graft
      dysfunction. A comparison was made with aortic valves prepared for grafting, with
      a view to assessing morphological and mineralogical characteristics as a
      potential preimplantation risk factor. METHODS: Valve leaflets were examined with
      light and scanning electron microscopy. Mineralization was assessed
      histochemically, and also physicochemically by atomic absorption spectroscopy
      (AAS). RESULTS: All explanted homograft valve leaflets revealed prominent
      degenerative changes seen as decreased surface area, fibrosis, mineralization and
      focal thrombosis. Substantial loss of endothelium and fibroblasts, reduced
      collagen bundles crimping, inflammation (81%) and disappearance of layered
      structure (59%) was identified. The elastic elements were relatively stable,
      though a gradual age-dependent loss was observed in both groups. Accelerated
      mineralization was seen in all explanted homografts; inorganic deposits were
      composed mainly of hydroxyapatite. Two types of mineralization were identified:
      large limited nodular structures, and diffuse mineral deposits. Homografts with
      moderately elevated mineralization, well-preserved layered structure and sporadic
      infective changes proved to have the greatest durability. Homograft durability
      was also affected by the difference in host and donor age. CONCLUSION:
      Preimplantation factors affecting pathological changes determining homograft
      durability included morphological status of the graft itself and donor age; host
      related factors included recipient age, endocarditis, native valve calcification,
      and host-donor matching (age difference between host and donor). A limited
      molecular mineralization may increase valvular durability, provided that no focal
      nodular calcifications exist that might adversely affect overall homograft
      integrity.

PMID- 14658817
TI  - Aortic root replacement with a new stentless aortic valve xenograft conduit:
      preliminary hemodynamic and clinical results.
AB  - BACKGROUND AND AIM OF THE STUDY: Beside aortic valve-sparing surgery, a composite
      graft, homograft or (more rarely) an autograft are the most common options to
      replace a diseased or destroyed aortic root in adults. Recently, a new stentless
      xenograft valved conduit (Shelhigh, No-React) was introduced in Europe. This
      totally biologic conduit is glutaraldehyde cross-linked, detoxified and heparin
      treated with No-React; this process eliminates residual glutaraldehyde and
      ensures stable tissue cross-linking. The initial clinical and hemodynamic results
      with this porcine valved conduit in the aortic position are presented herein.
      METHODS: Among 308 patients who underwent thoracic aorta surgery during a 30
      month period, 127 had aortic root repair or replacement. The Shelhigh stentless
      aortic valve conduit was implanted in 35 patients (30 males, 5 females; mean age
      68 +/- 7.2 years; mean body mass index 27.5 +/- 4.1 kg/m2). Of these patients, 15
      had aortic valve stenosis and ascending aortic aneurysm, 10 had a dilated aortic
      root with or without aortic regurgitation, four had acute aortic dissection type
      A, and six had a complex pathology (destructive endocarditis or re-do surgery).
      RESULTS: One patient with prosthetic valve endocarditis died on postoperative day
      1 from uncontrolled septicemia (30-day mortality, 2.7%). There were no conduit
      related adverse events in the surviving patients, but one re-exploration was
      required for bleeding in a re-do case. Transthoracic echocardiography was
      available in 30 patients after six months, and in 15 patients after 12 months.
      The mean gradient across the aortic valve was 8.5 +/- 5.1 mmHg (range: 6 to 14
      mmHg for conduit sizes 21 to 29 mm). CONCLUSION: The Shelhigh valved conduit
      shows promising hemodynamic properties. As the conduit contains no fabric or
      mechanical components, it is ideal for treatment of the infected aortic root, and
      an excellent alternative to homografts. In older patients, this conduit has the
      additional advantage that no long-term anticoagulation is required.

PMID- 14658818
TI  - The Quattro valve in rheumatic mitral valve disease: four-year follow up.
AB  - BACKGROUND AND AIM OF THE STUDY: There remains a great need for bioprosthetic
      valves in developing countries where monitoring of anticoagulation therapy is
      difficult. The study aim was to assess the intermediate outcome following mitral
      valve replacement with a stentless bovine pericardial quadrileaflet mitral
      (Quattro) valve. This valve maintains mitral annular-papillary continuity in
      patients with isolated severe rheumatic mitral valve disease. METHODS: Since
      December 1996, the Quattro valve has been implanted in 47 patients (mean age 34
      +/- 13 years; 16 (34%) aged <25 years) with rheumatic mitral valve disease. All
      patients were symptomatic, and in NYHA class II (n = 7), III (n = 30) or IV (n =
      10). Preoperatively, all patients underwent full clinical and routine
      echocardiographic assessment, as well as intraoperative transesophageal
      evaluation after valve implantation. At follow up visits, clinical and
      echocardiographic evaluations were carried out in each patient. RESULTS: After a
      mean follow up of 51 +/- 11 months, the overall mortality was 10.6% (five
      deaths). Five patients did not return for clinical follow up, but three of these
      are known to be alive and well. Of the 37 patients who returned for regular
      follow up, 32 remained symptomatically improved. Valve explantation was performed
      in two patients (4.2%) for prosthetic valve endocarditis. Two patients have
      deteriorated as a result of left ventricular dysfunction, and one patient has
      developed severe mitral regurgitation. Thromboembolism or clinically overt
      hemolysis has not occurred. One patient, who was receiving coumadin therapy for
      atrial fibrillation, died following a massive hematemesis. Serial one-year
      echocardiography data at one, two and three-year follow up intervals were
      available in 28 patients. These data confirmed no significant change in valve
      area or in mean diastolic gradient. Varying degrees of valve thickening were
      detected echocardiographically in 10 patients; four patients had clinically
      significant mitral stenosis (valve area <1.5 cm2). One valve was explanted for
      structural deterioration. CONCLUSION: Intermediate results after Quattro valve
      implantation in a relatively young population were satisfactory. However, long
      term follow up is mandatory to assess valve durability.

PMID- 14658819
TI  - Noise levels of closing sounds in vivo are equal for different bileaflet
      mechanical heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Patients with mechanical heart valves must
      endure the valve's closing sounds for the rest of their life. Sound pressure
      levels (SPLs) recorded show wide patient-to-patient variation, even for the same
      type of valve. The variation was attributed to body constitution variability and
      differences in hemodynamic status. It was hypothesized that aortic mechanical
      valves generate closing clicks which correlate in magnitude with hemodynamic
      parameters, such as the rate of relaxation of the left ventricle (dp/dt) and
      potential energy stored in the aortic windkessel. METHODS: Three different aortic
      mechanical heart valves were investigated in a porcine model (n = 9), namely St.
      Jude Medical, CarboMedics and ATS. Closing sounds were measured with a microphone
      placed in a portable anechoic chamber 10 cm above the exposed heart. Left
      ventricular pressure (LVP) and cardiac output were also measured. Different
      hemodynamic conditions were produced by intravenous infusion of isotonic saline
      and dobutamine. Volume regulation and atrial pacing were also applied. RESULTS:
      Different hemodynamic situations were established (cardiac output, 1.2-6.5 l/min;
      heart rate, 99-171 bpm). The measured mean SPLs were 49.5-53.9 dB(A), and there
      were no statistically significant differences in noise between the valves (p =
      0.8; one-way ANOVA). Likewise, only a weak relationship was identified between
      different hemodynamic parameters and the SPLs recorded. CONCLUSION: The SPLs of
      the investigated bileaflet mechanical heart valves did not differ significantly.
      Moreover, the SPL was only weakly related to LVP during closure and estimated
      stroke work.

PMID- 14658820
TI  - Two-dimensional fluid-structure interaction simulation of bileaflet mechanical
      heart valve flow dynamics.
AB  - BACKGROUND AND AIM OF THE STUDY: Mechanical heart valve implantation requires
      long-term anticoagulation because of thromboembolic complications. Recent studies
      have indicated that the relatively high wall shear stresses and negative pressure
      transients developed during the valve closing phase may be dominant factors
      inducing thrombus initiation. The study aim was a two-dimensional (2D) functional
      simulation of flow past bileaflet heart valve prosthesis during the closing
      phase, incorporating the fluid-structure interaction analysis to induce motion of
      the leaflets. METHODS: The fluid-structure interaction model used was based on
      unsteady 2D Navier-Stokes equations with the arbitrary Lagrangian-Eulerian method
      for moving boundaries, coupled with the dynamic equation for leaflet motion.
      Parametric analysis of the effect of valve size, leaflet density, and the
      coefficient of resilience at the instant of impact of the leaflet with the
      housing were also performed. RESULTS: Comparing the predicted motion of the
      leaflet with previous experimental results validated the simulation. The results
      showed the presence of negative pressure transients near the inflow side of the
      leaflet at the instant of valve closure, and the negative pressure transients
      were augmented during the leaflet rebound process. Relatively high velocities and
      wall shear stresses, detrimental to the formed elements in blood were present in
      the clearance region between the leaflet and valve housing at the instant of
      valve closure. CONCLUSION: The simulation can be potentially applied to analyze
      the effects of valve geometry and dimensions, and the effect of leaflet material
      on the flow dynamics past the valve prosthesis during the opening and closing
      phases for design improvements in minimizing problems associated with
      thromboembolic complications.

PMID- 14658821
TI  - A coupled fluid-structure finite element model of the aortic valve and root.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to develop a three-dimensional
      coupled fluid-structure finite element model of the aortic valve and root. This
      model extends previous purely structural finite element models, and represents a
      significant step toward realistic simulation of the complex interactions among
      tissue material properties and valvular function. METHODS: The aortic root and
      valve geometry were extracted from magnetic resonance images and imported into
      the LS-Dyna explicit finite element package. Leaflet and root tissue were modeled
      with elastic material properties, and blood was modeled as a Newtonian liquid. A
      dynamic, fully unsteady analysis was performed in which blood flow through the
      valve was computed along with the motion of the leaflets and root in response to
      standard physiologic pressure wave profiles. RESULTS: The opening and closing of
      the aortic valve under physiological loading conditions was successfully
      simulated, and feasibility of the model illustrated. The motion of the simulated
      leaflets was consistent with that seen in intact hearts. Analysis of fluid flow
      patterns revealed eddy structures in the sinus regions and flow into the coronary
      circulation. CONCLUSION: The addition of blood flow to structural models of the
      aortic valve and root is a significant advance in modeling, and allows a closer
      simulation of valvular function. The model will be used to further assess normal
      and abnormal physiology as well as the effects of surgical intervention.

PMID- 14658822
TI  - Indication of cavitation in mechanical heart valve patients.
AB  - BACKGROUND AND AIM OF THE STUDY: Cavitation may cause erosion of prosthetic heart
      valve material. The phenomenon has been extensively studied in vitro, and an
      association between the presence of cavitation bubbles and high-frequency
      pressure fluctuations (HFPF) has been established. In-vivo studies examining this
      phenomenon are scarce; hence, the study aim was to compare HFPF in patients with
      native, bioprosthetic or mechanical aortic valves, using both invasive and non
      invasive measuring techniques. METHODS: Measurements were carried out in 16
      patients implanted with a St. Jude Medical aortic valve; two control groups
      comprised 10 patients with normal aortic valves after coronary artery bypass
      surgery, and five patients implanted with a Carpentier-Edwards pericardial aortic
      bioprosthesis. HFPF were measured intraoperatively using a hydrophone placed near
      the aortic annulus, and postoperatively using the same hydrophone mounted in a
      specially designed water-filled sound chamber. The frequency spectrum was
      evaluated using Fast Fourier transformation, and the root mean square (RMS) value
      of the pressure signals was calculated in the frequency range 50-150 kHz.
      RESULTS: HFPF with intensities significantly above the noise floor were
      registered using both methods in the vicinity of mechanical heart valves. The RMS
      values of the HFPF for all three patient groups measured intra- and
      postoperatively disclosed a significant difference between the mechanical valves
      and the two control groups, indicating that there is no cavitation in the
      vicinity of the biological or the native valves. CONCLUSION: HFPF are present in
      the vicinity of mechanical aortic valves and can be measured in patients, both
      invasively and non-invasively. This indication of cavitation was not observed in
      patients with either native or bioprosthetic aortic valves.

PMID- 14658823
TI  - Double-valve Libman-Sacks endocarditis: an entity that demands special
      consideration.
AB  - BACKGROUND AND AIM OF THE STUDY: Valvular heart disease, with a propensity for
      the left valves, is the most important cardiac manifestation of systemic lupus
      erythematosus (SLE). Libman-Sacks endocarditis complicating SLE has rarely been
      reported to cause hemodynamically significant valvular lesions necessitating
      valve replacement. METHODS: This report describes a young woman with moderate
      aortic regurgitation and moderate to severe mitral regurgitation due to Libman
      Sacks endocarditis. RESULTS: Treatment consisted of aortic and mitral valve
      replacement with mechanical prostheses due to intractable heart failure. The
      patient's recovery was uneventful. CONCLUSION: A literature survey disclosed only
      nine reports of double-valve replacement in patients with SLE. These findings,
      together with the present experience, suggest that valvular disease in SLE
      changes frequently with time, appears to be temporally unrelated to the other
      clinical features of SLE, and is associated with substantial morbidity and
      mortality. Corticosteroid treatment may slow the progression of valvular
      regurgitation. If surgery is necessary, replacement with a mechanical valve may
      be better than with a bioprosthesis.

PMID- 14658824
TI  - Health and the environment in the Tari area.

PMID- 14658825
TI  - A history of Huli society and settlement in the Tari region.
AB  - The Huli community of the Tari region has been profoundly influenced through
      contact with the wider world since the 1930s. However, the trajectories of change
      and the basic structural properties of Huli society need to be understood within
      the context of much longer-term histories of transformation. This paper briefly
      reviews evidence drawn from a range of disciplines for the history of Huli
      settlement in the Tari region, and the nature of changes in Huli society both
      before and after contact with the colonial government.

PMID- 14658826
TI  - The ecology of Huli subsistence agriculture.
AB  - A detailed study of the ecology of subsistence agriculture in the Tari Basin was
      conducted to investigate the stability of intensive agroecosystems in the
      highlands of Papua New Guinea. The highly intensive agricultural systems that
      have evolved in the wetland environments in the lowest parts of the basin were
      found to be extremely stable and capable of further intensification. Both soil
      fertility and sweet potato yields showed no signs of degradation even though some
      areas had been under continuous cultivation for hundreds of years. In the dryland
      environments with volcanic ash soils there was evidence of ecological instability
      in the form of declining soil fertility and sweet potato yields over time and the
      progressive replacement of forest vegetation with grasslands having a much lower
      biomass and nutrient content. Higher altitude dryland environments were the most
      susceptible to degradation due to lower fertility soils, higher rainfall and
      higher rates of soil loss by erosion. The Huli people have responded to these
      differences in ecological stability by concentrating their agricultural
      activities increasingly on to the more fertile wetland areas. Much of this
      movement into the lower parts of the basin is thought to have occurred in the
      period since European contact, over the last 50 years. These findings have
      implications for much of the Papua New Guinea highlands where volcanic ash soils
      occur. Although these soils are highly suitable for growing sweet potato and have
      been able to support large rural populations with their pigs, they are unable to
      remain productive under continuous cultivation even though the cropping practices
      of most highland groups are well adjusted to conserving soil fertility and
      maximizing crop yields. The chemical fertility of volcanic ash soils is being
      progressively depleted and much greater efforts are needed to promote the
      restoration of soil fertility during the fallow period. Much greater emphasis is
      needed on improving fallow practices such as the promotion of woody regrowth and
      forest regeneration and the growing of leguminous cover crops to protect soils
      against erosion and to provide a large volume of nutrient-rich plant material
      suitable for composting.

PMID- 14658827
TI  - Pneumonia vaccine trials at Tari.
AB  - Pneumonia is the commonest cause of death of children in Papua New Guinea (PNG).
      At Tari pneumonia is most commonly caused by Streptococcus pneumoniae and
      Haemophilus influenzae, which set up rapid severe infections in the lungs that
      require urgent treatment. In rural PNG, however, treatment is often delayed.
      Penicillin-resistant forms of these bacteria are on the increase. It is therefore
      important to have another means of protection against this serious disease. This
      paper describes three field trials of a vaccine against the commonest serotypes
      of S. pneumoniae found in PNG. The trials show that a pneumococcal vaccine can
      prevent deaths from uncomplicated acute lower respiratory tract infection in
      small children and adults. It is likely that the vaccine does this by limiting
      the replication of bacteria in the lungs and thus limiting their spread to other
      parts of the body.

PMID- 14658828
TI  - Demography and causes of death among the Huli in the Tari Basin.
AB  - Monthly demographic surveillance by local reporters was continuous in the Tari
      Basin from 1971 until 1995 and cause of death was determined primarily by verbal
      autopsy. In 1982 the de jure population was 26,500, 15% aged less than 5 years.
      Crude birth rate was 34/1000/annum in 1980-1984; from 1977 to 1983 crude
      mortality rate was 15/1000/annum and life expectancy at birth 50 years. Infant
      mortality fell from 160 in the 1920s to 72/1000 livebirths in the 1970s, the
      greatest decline occurring between 1952 and 1971 when antibiotics became widely
      available. Respiratory disease (particularly chronic lung disease in adults)
      accounted for 39% of all deaths, and pneumonia for 50% and 33% of infant and
      toddler deaths respectively. Very few deaths from pigbel have occurred since the
      introduction of pigbel vaccine. Initially childhood mortality from diarrhoea
      declined following introduction of an oral rehydration program but subsequently
      rose when medical attention was no longer sought and children were inadequately
      treated at home. The higher mortality in the lower-lying Iumu area was attributed
      to malaria. Since the opening of the Highlands Highway in 1981, there has been a
      dramatic increase in short-term movement of both men and women in and out of Tari
      resulting in increased incidence of sexually transmitted diseases and viral
      infections such as measles. If restored, the Tari Research Unit could continue to
      play a key role in assisting the Department of Health in making decisions on
      appropriate interventions to improve the quality of life of Papua New Guineans.

PMID- 14658829
TI  - Huli oral health.
AB  - The Tari oral health study was conducted in 1985 and aimed to provide an oral
      health profile of a rural highlands community. The sample was selected from the
      database of the Tari Research Unit, Southern Highlands Province, Papua New Guinea
      and consisted of 815 Huli people aged from 3 to 64 years, in seven age groups,
      who were examined for oral health status and had completed an interview
      questionnaire. A wide range of oral health status was seen, ranging from
      excellent to very poor. Dental caries and periodontal disease were common in the
      population. Oral habits such as smoking and betelnut chewing were associated with
      an increase in leukoplakia, which may lead to oral cancer in some people. Dental
      caries varied in prevalence and severity. Higher decayed, missing and filled
      teeth scores in the primary teeth of young children were associated with
      defective tooth formation (hypoplasia) linked to maternal and childhood illnesses
      and nutritional deficiencies. Older adults had the worst oral health, with the 45
      64 year old group having a caries prevalence of 95% and a decayed, missing and
      filled teeth score of 14.7. Root surface caries, seen as a consequence of poor
      oral hygiene and gum recession, was the major site of caries attack in the older
      Hull. The public oral health services are unable to reach a large proportion of
      the rural population, and people continue to use traditional herbal and folk
      remedies. Many seek the skills of local tooth extractors who use six-inch nails
      with no anaesthetic.

PMID- 14658830
TI  - Nutrition in Tari.
AB  - The growth of children in Tari is poorer than the growth of children in two
      thirds of the highlands districts of Papua New Guinea. The important proximal
      determinants of these levels of growth in Tari are birthweight, food and nutrient
      intake and disease episodes. Birthweights in Tari are lower than in a number of
      other highlands centres and this is likely to be an important determinant of
      postnatal growth and disease, particularly for those whose birthweights are below
      2500g. The overall effect of child feeding practices in Tari is that energy and
      protein intakes may be marginal after the first few months of life and contribute
      to the low levels of growth. Episodes of illness (young children experience an
      average of 4 episodes in the first year) decrease nutrient intake and increase
      nutrient requirements; this, combined with the failure to increase food intake
      during the convalescent period, means that the overall result of an episode of
      disease is a decrease in growth. There are functional consequences of this
      pattern of growth in Tari: low-birthweight children and those who are
      malnourished have a higher mortality rate than those of normal birthweight and
      growth, and short children have delays in achieving gross motor development
      milestones.

PMID- 14658831
TI  - Birthweight and environment at Tari.
AB  - The weights at birth of 4767 children born in the Tari area between 1979 and 1986
      were analyzed after the children had been allocated to seven environmental zones.
      The environments differ in the quality of land from which the staple food, sweet
      potato (Ipomoea batatas), is produced. Mean birthweight varies significantly by
      environment. Women do much of the day-to-day agricultural work. It is argued that
      women living in the poorer quality environments produce less food, suffer chronic
      malnourishment and have lighter babies as a result. From time to time, however,
      El Nino-Southern Oscillation (ENSO) events can result in sharp and severe
      shortages in food in both favoured and poorer environments. The cause is complex
      and involves rainfall and women's work rates. These food shortages cause
      decreases in mean birthweight of up to 285 g for one or more years and an
      increase in the rate of low-weight births, even in the best environments. The
      implications for the long-term improvement of health are raised.

PMID- 14658832
TI  - Nutritional adaptation of women in contrasting agricultural environments in Tari,
      Papua New Guinea.
AB  - The energy expenditure, food consumption and anthropometry of two groups of Hull
      women are described. The group occupying the highly productive drained margins of
      the Haeapugua Swamp at Weinani have significantly higher intakes of energy and
      protein than those at Heli on the Paijaka Plateau. However, both groups of women
      expend similar amounts of time and energy in agricultural activities. The
      differences are explained by the contrasting quality of agricultural land at each
      place. Production per hectare at Heli is only around half of that at Weinani. It
      is concluded that the nutritional health of Heli women is compromised. This is
      probably the cause of the significantly lower mean birthweights of children born
      to women living on the Paijaka Plateau.

PMID- 14658833
TI  - District health care at Tari until 1991.
AB  - This paper traces the history and development of health care at Tari up until
      1991. It focuses on Tari District Hospital as the hub of district health care and
      describes conditions for health delivery in the district. Patterns of morbidity
      and mortality are contrasted between the hospital and the community, using Tari
      Research Unit data for comparison. Health improvements achieved over the two
      decades before 1991 are due mainly to curative health care. However, the pattern
      of disease has changed little. Pneumonia is highly prevalent and is associated
      with high case fatality rates among infants in hospital. Improvements in health
      status are only likely if living conditions improve and community-based responses
      develop. The implementation of a primary health care approach, and specific
      measures to improve hospital and health service outcomes would also assist.
      Health services are under severe pressure from population growth coupled with
      declining budgets, the breakdown in law and order, and the burdens of HIV/AIDS
      and noncommunicable disease.

PMID- 14658834
TI  - Social and economic conditions at Tari.
AB  - A social and economic survey was conducted in 1984 to assess the impact of
      development at Tari and to supplement the demographic data being collected by the
      Tari Research Unit. Of 1604 adults aged 17 years and over selected from the
      demographic database, 1389 were interviewed and information was collected on the
      remainder from informants. The survey reveals an uneven pattern of change, with
      men living close to the town most advantaged in terms of education, employment,
      diet and possessions, and women in remote areas the least advantaged. There was,
      however, some evidence that peripheral parts of Tari were catching up with those
      in the centre. Observations since 1984, and some data collected in 1998, suggest
      that law and order problems and the decline in government services have led to a
      stagnation in social progress at Tari. This is despite considerable expansion of
      the district economy due to payments and remittances from resource projects
      operating in and around Tari. Women's educational status has nonetheless improved
      to some extent. Better governance and the restoration of services are required if
      the socioeconomic status of Tari people is to improve.

PMID- 14658835
TI  - Sexually transmitted infections: a medical anthropological study from the Tari
      research unit 1990-1991.
AB  - This paper describes medical anthropological research conducted while I was based
      at the Tari Research Unit for six months in 1990-1991. The research aimed to gain
      a deeper understanding of the social factors surrounding the transmission of
      sexually transmitted infections, which had escalated following a local gold rush
      in 1989. Although HIV/AIDS was a very minor health issue in Papua New Guinea at
      that time, medical staff were aware of the likelihood of the disease becoming
      prevalent in the highlands in the near future. The research indicated that many
      people regarded sexually transmitted infections (STIs) as a nuisance, rather than
      a serious health risk. Discussions with chronic sufferers revealed that they were
      more concerned about the dangers of infertility than the immediate effects of the
      infections. The paper considers the risk-taking that the people of Tari, the
      Huli, were prepared to accept and suggests ways in which these risks might be
      minimized.

PMID- 14658836
TI  - Antenatal utilization, family planning and fertility preferences in Tari.
AB  - This paper reports on the results of a questionnaire on antenatal utilization,
      family planning and fertility preferences carried out on 2560 women in Tari in
      1998. There is a very high level of utilization of antenatal and delivery
      services. There is also a broad knowledge of family planning methods, but very
      low uptake of these services. Part of the reason for this lies in high fertility
      preferences among women in Tari, part in a lack of confidence regarding the
      methods, and part in male opposition to their use. Comparison with elsewhere in
      Papua New Guinea confirms that health service utilization and fertility
      preferences are high, and family planning uptake is low in Tari. The decline in
      health services and the collapse of law and order in Tari bodes ill for the
      future of a family planning program in a district in which the need for such
      services is rising, due to the effects of population pressure on the environment.

PMID- 14658837
TI  - Passenger-women: changing gender relations in the Tari Basin.
AB  - Papua New Guinea is in the early stages of an HIV/AIDS epidemic. It is important
      to understand how the sexual behaviour of Huli men and women will influence the
      form of the epidemic in the Tari area. High numbers of single and married men
      migrating out of the Tari area in search of employment, returning with sexually
      transmitted infections, are one cause for concern. Another is the emergence of a
      form of prostitution in the Tari area. This paper describes an unusual aspect of
      female sexual behaviour at Tari in which some women become sexually promiscuous,
      behaving in a manner that could be labelled prostitution. This behaviour
      scandalizes their families and results in a debasing of their value as brides.
      However, the women involved do not see their actions as being part of any form of
      sex work. Rather, they participate in this behaviour because they are frustrated
      and angry. The women feel their male kin have not fulfilled customary obligations
      to them as women; often the women have been raped and their assailants neither
      apprehended nor punished. As a result the women have come to believe that the
      meaning and function of bridewealth marriage has changed such that women are like
      commodities to be bought and sold. They see their behaviour as a form of revenge
      on their families and on a culture that seemingly no longer values them as
      persons.

PMID- 14658838
TI  - The family health and rural improvement program in Tari.
AB  - The Family Health and Rural Improvement Program (FHRIP) grew out of 25 years of
      research activity in Tari. Between 1995 and 2000 FHRIP assisted over 300 families
      in 20 communities in Tari to acquire a water supply, sanitation, nutritional
      gardens and small livestock, and provided health education. The program
      demonstrated that with appropriate assistance local people could improve their
      health and start small projects that promise real development in their
      communities. The extension of this experience is occurring under Community-Based
      Health Care in several highlands provinces. However, FHRIP had to overcome many
      internal and external obstacles, and more commitment from the public sector,
      together with long-term assistance from aid agencies, is required if such
      initiatives are to grow and flourish.

PMID- 14658839
TI  - Sequence analysis of infectious bursal disease virus isolates from India:
      phylogenetic relationships.
AB  - Prevalence of infectious bursal disease (IBD) among chickens in different parts
      of Tamil Nadu, India, has been studied by collection of bursal samples from
      suspected flocks and by performing reverse transcription-polymerase chain
      reaction (RT-PCR) for amplification of a specific product of 474 bp from the
      variable region of the VP2 gene. Among 53 bursal samples examined by RT-PCR, 40
      showed a positive reaction. The amplified products were subjected to nucleotide
      sequencing and the obtained sequences were compared with those of IBD virus
      (IBDV) vaccine strain Georgia, the classical virulent strain 52/70 and the very
      virulent Japanese OKYM strain. Nucleotide homology data indicated that all the
      Tamil Nadu isolates showed homology ranging from 91 to 99.6% among themselves.
      When compared with the very virulent Japanese OKYM strain, four isolates grouped
      with that strain. Majority of the isolates clustered with the very the virulent
      OKYM strain as evident from phylogenetic analysis performed using the MEGA
      program. Comparison of the deduced amino acid sequences of IBDV isolates with
      those of the vaccine strain Georgia, the classical virulent strain 52/70 and the
      very virulent strain OKYM also revealed the presence of conserved serine-rich
      heptapeptide sequence in most of the isolates. Results of this study indicate
      that majority of the IBDV isolates are very virulent, which is evident from heavy
      mortality that has been reported in few flocks of poultry in spite of regular
      vaccination.

PMID- 14658840
TI  - Acute diarrhea in Paraguayan children population: detection of rotavirus
      electropherotypes.
AB  - Group A rotavirus infections were detected in 93 of 410 fecal samples from
      children with acute diarrhea, admitted in three main hospitals of Asuncion,
      Paraguay, from August 1998 to August 2000. Most of the rotavirus-infected
      patients were admitted during the winter season in the three epidemic years. The
      rotavirus infection rate was highest in infants from 6 to 23 months of age. In
      the 93 samples examined, 10 different rotavirus electropherotypes were
      recognized, but two of them largely predominated. Only one sample showed a short
      electropherotype pattern, thus indicating a minor involvement of the rotavirus
      subgroup I in rotaviral acute diarrhea in the area and the time during which the
      survey was carried out.

PMID- 14658841
TI  - Protection of mice against experimental Japanese encephalitis virus infections by
      neutralizing anti-glycoprotein E monoclonal antibodies.
AB  - Neutralizing monoclonal antibodies (MAbs) to glycoprotein E (gpE) of Japanese
      encephalitis (JE) virus given intraperitoneally (i.p.) (0.1 ml of immune ascitic
      fluid (AF) diluted 1:10 per mouse) to about 4-week-old Swiss mice 1 day prior or
      2 days after the virus challenge (100 LD50 of JE virus administered
      intracerebrally (i.c.)) resulted in a decreased mortality along with an increased
      survival of the animals as demonstrated by the HAI-positive virus-specific (Hs)
      MAbs. The protective effect produced by four Hs MAbs was maximum when given 1 day
      prior the virus challenge, while other, namely HAI-positive flavivirus cross
      reactive (Hx) and HAI-negative virus-specific (NHs) MAbs did not produce any
      effect. Interestingly, one of the two NHs MAbs, namely NHs-1 showed a reduced
      survival of mice given the MAb 2 days after the virus challenge. Administration
      of combinations of two or more Hs MAbs may be recommended due to their possible
      enhanced protection against JE virus infections in mice.

PMID- 14658842
TI  - A rapid and effective RNA release procedure for virus detection in woody plants
      by reverse transcription-polymerase chain reaction.
AB  - A rapid and effective RNA release procedure (RNA-RP) for detection of the Apple
      stem pitting virus (ASPV) and the Apple stem grooving virus (ASGV) in woody
      plants by reverse transcription-polymerase chain reaction (RT-PCR) was developed.
      RNA-RP released RNA into crude homogenate. RNA-RP was compared with classical
      phenol/chlorophorm extraction of RNA. The RT-PCR detection of ASPV and ASGV was
      shown to be similar by both the RNA preparation procedures. RNA-RP in contrast to
      the classical phenol/chloroform procedure represents a reliable and easy-to hand
      protocol convenient for routine virus detection. Leaf tissues, especially dormant
      bud leaves and leaves during blossom, were shown to be the most optimal material
      for detection of these viruses, irrespective of the used RNA preparation
      procedure.

PMID- 14658843
TI  - Polymerase chain reaction assay for Cydia pomonella granulovirus detection in
      Cydia pomonella population.
AB  - The polymerase chain reaction (PCR) assay was successfully used to identify Cydia
      pomonella granulovirus (CpGV) in larvae of Cydia pomonella L. (codling moth). PCR
      with the primers CpGV-2A/CpGV-2B and CpGV-3A/CpGV-3B was found suitable for
      detection of CpGV. The primers Cp-I/Cp-II and Cp-III/Cp-IV were able to identify
      the transposable element TCp3.2 in C. pomonella larvae. The presence of CpGV in
      the larvae from orchards,which had been infected with CpGV was tested during 2
      years post infection. (p.i.). CpGV was found in as many as 15% of the surviving
      larvae 1 year p.i. in one location. The virus was not detected in CpGV-infected
      orchards 2 years p.i. or in natural C. pomonella populations. This result
      suggests a poor persistence of CpGV in surviving C. pomonella individuals and its
      slow spread in a natural host population. One the other hand, the presence of a
      transposable element, transposon TCp3.2 may correlate with virus redistribution
      in this insect population.

PMID- 14658844
TI  - Detection of immediate early protein ICP27/IE63 and thymidine kinase in the
      course of reactivation of latent herpes simplex virus 1 infection.
AB  - We followed the kinetics of reactivation of latent Herpes simplex virus 1 (HSV-1)
      infection established in rabbits by corneal route. The corresponding trigeminal
      ganglia (TG) were cultured and the culture medium was examined at daily intervals
      for release of infectious virus. Sections from the cultured TG fragments were
      stained with antisera against non-structural proteins such as the immediate early
      (IE) protein ICP27 and the early (E) proteins thymidine kinase (TK), the large
      subunit of ribonucleotide reductase (RR1), the ori-binding protein OBP and with a
      human serum obtained from volunteers immunized with an experimental subunit HSV-1
      envelope (env) vaccine containing late structural proteins gB1, gC1, gD1 and gG1
      (env antiserum). By indirect immunofluorescence (IF) test, ICP27 was detected in
      a few neurons from day 1 post explantation (p.e.), while TK was observed in
      neurons from day 2 p.e. Fluorescence with the human env antiserum was seen at day
      3 p.e. The RR1 and OBP antisera stained productively infected Vero cells from 3
      and 4 hrs post inoculation (p.i.), respectively. However, these sera showed no IF
      in cultured ganglion fragments at any interval examined. Our results showed the
      same cascade of HSV-1 IE and E protein expression during productive infection and
      reactivation in vitro.

PMID- 14658845
TI  - Sexually transmitted infections among prostitutes in Bratislava, Slovakia.
AB  - Sera from 18 prostitutes from Bratislava were examined for the presence of
      antibodies to several sexually transmitted pathogens, namely Herpes simplex virus
      2 (HSV-2), Human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2), Hepatitis B
      and C viruses (HBV and HCV), Chlamydia trachomatis, and Treponema pallidum.
      Results of this screening indicated that 11 prostitutes (61%) carried 1 or more
      sexually transmitted infections. The most prevalent antibodies were directed
      against HSV-2 (9 cases, i.e. 50%), which represents the most common sexually
      transmitted infection agent.

PMID- 14658846
TI  - Isolates of infectious bursal disease virus from India are of very virulent
      phenotype.
AB  - Four Indian field isolates, a classical virulent and an attenuated vaccine
      strains of Infectious bursal disease virus (IBDV) have been characterized by
      sequence analysis of part of the VP1 gene (from nucleotide 1538-1979) comprising
      one of viral RNA dependent RNA polymerase motifs. Sequence alignment of these
      viruses with reported viruses of other countries revealed Indian IBDV field
      isolates to be 100% similar to very virulent Japanese (OKYM), European (UK661)
      and Bangladesh (BD3/99) IBD viruses at amino acid level, whereas they had 0.2
      0.9% divergence at nucleotide level. Out of the total 24 nucleotide changes found
      in the Indian field isolates, as well as reported very virulent viruses, only one
      resulted in amino acid change S-P at 562 position. The Indian field isolates
      displayed nucleotide divergence of 10.6-11.6% and amino acid divergence of 2.8
      3.5% from the classical virulent and attenuated vaccine strains. The RNA
      dependent RNA polymerase motif from amino acid 528-541, present in the sequence
      analyzed, was conserved among all the viruses, irrespective of pathotype and
      serotype. In the phylogenetic tree, based on nucleotide sequence, Indian field
      viruses were grouped with reported very virulent viruses in one lineage whereas,
      classical virulent, attenuated vaccine and serotype 2 strains formed part of the
      second lineage. But in the phylogenetic tree based on amino acid sequence
      alignment, the serotype 2 strain OH grouped with Indian field isolates and
      reported very virulent viruses in one lineage and classical virulent and
      attenuated vaccine strains formed the second lineage.

PMID- 14658847
TI  - Detection of egg drop syndrome 1976 virus by polymerase chain reaction and study
      of its persistence in experimentally infected layer birds.
AB  - Polymerase chain reaction (PCR) assay was developed for the detection of Egg drop
      syndrome 1976 (EDS-76) virus in tissues, namely in the uterus, spleen and buffy
      coat. It was also used to study the persistence of the virus in tissues of
      experimentally infected layer birds. The PCR assay could detect as little as 10
      fg of purified EDS-76 viral DNA. It also amplified the DNA of Fowl adenovirus
      serotypes 4 (FAV-4) and 8 (FAV-8). The virus persisted in the uterus up to day 21
      post infection (p.i.). Detection of EDS-76 viral DNA in the buffy coat could be
      useful for studying the occurrence of the respective disease in layer bird
      flocks.

PMID- 14658848
TI  - Serological evidence for Japanese encephalitis virus and West Nile virus
      infections in water frequenting and terrestrial wild birds in Kolar District,
      Karnataka State, India. A retrospective study.
AB  - In a serological survey of birds in a Japanese encephalitis (JE) endemic area of
      Kolar District, Karnataka State, India, 859 bird sera were tested by
      hemagglutination-inhibition test (HIT) for JE encephalitis and West Nile
      encephalitis (WNE) viruses. Only 2 (0.002%) and 178 (20.72%) sera were positive
      for JE virus (JEV) and WNE virus (WNV), respectively. Only 160 (18.63%) of 859
      sera could be subjected to neutralizing test (NT). Of these, 20 (12.50%) and 62
      (38.75%) were positive for JEV and WNV antibodies, respectively. These findings
      indicate that bird species such as Pond Herons and Little Egrets among ardeid
      birds and Grey Partridges and Quails among terrestrial birds are infected with
      JEV and WNV and play probably a role in the maintenance of these viruses in the
      abovementioned part of India.

PMID- 14658849
TI  - Synergism between the nucleopolyhedroviruses of Autographa californica and
      Trichoplusia ni.
AB  - Previous observations on high virulence of Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) and Trichoplusia ni single nucleopolyhedrovirus
      (TnSNPV) acting together led us to test possible synergism between these two
      nucleopolyhedroviruses (NPVs) on cabbage looper larvae. Because synergism between
      AcMNPV and the Trichoplusia ni granulovirus (TnGV) has been well established
      before, these two viruses were included in this study as a positive control. Each
      virus was assayed separately on first-instar cabbage looper and their LC50s were
      estimated at 2.33, 0.39 and 462 OB/mm2 diet for AcMNPV, TnSNPV and TnGV,
      respectively. LC50s of AcMNPV mixed with sub-lethal concentrations of TnSNPV and
      TnGV increased 8 and 10.7 times, respectively. Synergism between the viruses was
      analyzed by the ANOVA test for the LC50s, the Plackett and Hewlett's joint-action
      rate test, and the Tammes-Bakuniak graphic method. All three analyses
      corroborated the synergism between the viruses. The presence of a putative
      enhancin in the TnSNPV was analyzed by Southern blot hybridization, using a 1.5
      kbp KpnI fragment from the TnGV vef gene as a probe. No hybridization was
      observed. The occurrence of a new putative synergistic factor in TnSNPV is
      discussed.

PMID- 14658850
TI  - First confirmed sheep scrapie with A136R154Q171 genotype in Slovakia.
AB  - The first confirmed evidence of scrapie in Slovakia was demonstrated in one sheep
      of the autochthonous Merino breed from the southeastern part of the country. The
      reported scrapie was diagnosed during compulsory transmissible spongiform
      encephalitis (TSE) screening of sheep over 9 months of age assigned for
      consumption. The positive ewe was 5-year-old, which did not show any clinical
      signs of scrapie. The presence of the proteinase-resistant prion protein (PrP) in
      brain was proved independently by two laboratories using two different
      immunochemical screening systems, namely the Prionics Check (Western blot
      analysis) and Enfer TSE enzyme-linked immunosorbent assay (ELISA). In addition,
      the genotyping analysis of PrP gene demonstrated the presence of PrP genotype
      from the high risk group R4. The affected sheep was homozygous for the allele
      PrP(ARQ) (ARQ/ARQ) coding for alanine (A), arginine (R) and glutamine (Q) at
      three most relevant codons (136, 154 and 171, respectively). The healthy sister
      of the positive ewe was heterozygous in the PrP locus and carried alleles
      ARQ/ARR.

PMID- 14658851
TI  - Improved detection of Arabis mosaic virus in grapevine and hop plants.

PMID- 14658852
TI  - A comparison of transient-evoked otoacoustic emissions and automated auditory
      brainstem responses for pre-discharge neonatal hearing screening.
AB  - The aim of this study was to compare two hearing-screening methods in well
      newborn infants within the postnatal ward environment prior to discharge. Eighty
      one newborn infants underwent one-step hearing screening by measurement of
      automated auditory brainstem responses (aABRs), using the ALGO-3 screener. These
      were compared with a further cohort of 81 neonates who underwent two-step
      screening using transient-evoked otoacoustic emissions (TEOAEs) followed by aABR.
      The pass rate was 78/81 (96.3%) for the one-step screen, 74/81 (91.4%) for the
      two-step screen, and 54/81 (66.7%) for TEOAE alone. There was no significant
      difference between cohorts in time required to complete the screening protocol.
      We conclude that pre-discharge hearing screening of newborn infants on the
      postnatal ward is feasible and acceptable. Use of TEOAE alone for pre-discharge
      screening is associated with an excessively high false-positive rate. At our
      institution, one-step screening resulted in a lower referral rate compared with a
      two-step approach. The performance of aABR screening may be affected by prior
      TEOAE screening.

PMID- 14658853
TI  - Otoacoustic emissions and tympanometry in a general adult population in Sweden.
AB  - The present study concerns a general adult population in Sweden, not exposed to
      hazardous occupational noise. Tympanometry and spontaneous (SOAE), transient
      evoked (TEOAE) and distortion-product (DPOAE) otoacoustic emissions were
      investigated in 493 randomly selected men and women aged from 20 to 79 years.
      Effects of gender, age, ear side and middle ear state were determined, with and
      without adjusting for hearing threshold level. No statistically significant
      effects on middle ear pressure or compliance were present. For TEOAEs and DPOAEs,
      the effect of gender and age was statistically significant (p < 0.01), with
      larger signal levels for female subjects and young subjects, even after adjusting
      for hearing threshold level. No effect of middle ear pressure on otoacoustic
      emissions was present, but high middle ear compliance was associated with low
      emission levels (p < 0.01). Reference data for middle ear compliance and pressure
      and prevalence data on SOAEs, TEOAEs and DPOAEs for male and female subjects in
      different age groups were determined. Mean signal levels of TEOAEs and DPOAEs are
      presented.

PMID- 14658854
TI  - Application of the TEN test to hearing-impaired teenagers with severe-to-profound
      hearing loss.
AB  - Hearing impairment is often associated with damage to the hair cells of the
      cochlea. An area of the cochlea with complete loss of function of inner hair
      cells is known as a 'dead region'. Dead regions can be identified by measuring
      detection thresholds for pure tones in quiet and in threshold-equalizing noise
      (TEN). So far, the TEN test has only been used to identify dead regions in adults
      with moderate-to-severe hearing impairment. The aim of this study was to assess
      problems in applying the TEN test to teenagers with longstanding severe-to
      profound sensorineural hearing impairment, and to assess the prevalence of dead
      regions in this population. The subjects had a mean age of 14 years, and there
      were 13 females and 20 males. The stimuli for the TEN test were derived from a
      CD, whose output was routed via a GSI-16 audiometer and an amplifier to
      Sennheiser HD580 earphones. For each ear of each subject, both absolute
      thresholds and masked thresholds in the TEN were measured. For the majority of
      ears, the results were in-conclusive at some frequencies, due to the maximum
      output of the audiometer being reached when measuring the absolute or masked
      threshold. In almost all cases, the diagnosis was uncertain at some frequencies
      because the TEN could not be made sufficiently intense to produce significant
      masking. However, for 23 (70%) subjects, the criteria for a dead region at medium
      or high frequencies were met in at least one ear. For eight (35%) of these
      subjects, the criteria were only just met. Sixteen of the 24 subjects with a
      congenital hearing impairment, and four of the five subjects with an acquired
      impairment, met the criteria for a dead region. The results suggest that dead
      regions are relatively common among teenagers with a longstanding hearing
      impairment.

PMID- 14658855
TI  - Otosclerosis: exclusion of linkage to the OTSC1 and OTSC2 loci in four Italian
      families.
AB  - Otosclerosis is the single most common cause of hearing impairment among adult
      caucasians. Little is known about its aetiology and its molecular aspects. Until
      now, genetic linkage in otosclerosis has been demonstrated in an Indian family
      and a Belgian family, showing the presence of two otosclerosis loci, OTSC1 and
      OTSC2, respectively. Linkage analysis has never been applied to Italian
      otosclerotic families. We have collected four multigenerational Italian
      otosclerotic families that show dominant transmission for the pathology. Here, we
      report a detailed audiological analysis of these families and a genetic linkage
      study on the OTSC1 and OTSC2 loci. Statistical analysis revealed the absence of
      linkage between the disease in our families and the OTSC1 and OTSC2 loci. These
      data strongly suggest the presence of one or more additional loci for
      otosclerosis, which still need to be defined.

PMID- 14658856
TI  - Expectations about hearing aids: demographic and audiological predictors.
AB  - The Expected Consequences of Hearing Aid Ownership inventory (ECHO) is a 14-item
      questionnaire for measuring expectations about hearing aids. The objectives of
      this study were to evaluate the ECHO questionnaire used in the Danish National
      Hearing Health Service in terms of reliability and validity; to use the inventory
      to assess the patients' pre-fitting expectations in different domains, to gain
      information on possible predictors for the magnitude of expectations, and to
      evaluate whether first-time users had realistic expectations. The questionnaire
      was administered to 805 consecutive patients, and responses were received from
      47.7%, representative for the population examined in the department. The median
      age was 74.1 years, with an even distribution of males and females, and a median
      better-ear pure-tone average (0.5-4 kHz) of 41.3 dB HL. The results showed that
      the questionnaire had acceptable reliability and validity when the original
      subscales were rearranged. The pre-fitting expectations with regard to the
      positive effect of amplification and different aspects related to the hearing aid
      and service were, overall, very high. Age and hearing status were predictors of
      the magnitude of expectations related to the hearing aid and the service. In
      first-time users, unrealistic positive expectations were found with regard to
      potentially negative features of hearing aids.

PMID- 14658857
TI  - Effects of a hearing protection campaign on the discotheque attendance habits of
      high-school students.
AB  - This study investigated whether a hearing education campaign would prompt
      adolescents to display hearing-protective behaviour when attending a discotheque.
      A sample of 169 high-school students participated in the campaign. A
      questionnaire was administered to them before and 1 year after the campaign,
      asking for the frequency of discotheque attendance within the past 6 months, and
      whether they used earplugs in the discotheque. The percentage of subjects who
      went to discotheques more than 10 times within 6 months decreased from 34% to 24%
      after the campaign. The overall difference between pre- and post-campaign
      frequencies of discotheque attendance, however, was not significant. The
      percentage of subjects using earplugs in the discotheque rose from 0% before to
      3.7% after the campaign. In essence, the campaign had little effect in inducing
      hearing-protective behaviour in adolescents when attending discotheques. The need
      for sound level limitations in discotheques is highlighted.

PMID- 14658858
TI  - Peak-to-peak equivalent sound pressure level.

PMID- 14658859
TI  - A non-radical chain mechanism for oxygen atom transfer with a thiorhenium(V)
      catalyst.
AB  - The compound MeRe(S)(mtp)(PPh3), 2, where mtpH2 is 2-(mercaptomethyl)thiophenol,
      was used to catalyze the reaction between pyridine N-oxides, PyO, and
      triphenylphosphine. The rate law is -d[PyO]/dt=kc'[2].[PyO](1/2), with kc' at
      25.0 degrees C in benzene=0.68 (4-picoline N-oxide) and 3.5x10(-3) dm(3/2) mol(
      1/2) s(-1) (4-NO2-pyridine N-oxide). A chain mechanism with three steady-state
      thiorhenium species as chain carriers is implicated.

PMID- 14658860
TI  - Ni(III) complex of an N-confused porphyrin inner C-oxide.
AB  - A novel, structurally characterized Ni(III) complex of an N-confused porphyrin
      inner C-oxide has been synthesized from the oxidation of a Ni(II) N-confused
      porphyrin using OsO4. Crystal data: C53H40N5NiO.CH2Cl2, monoclinic, space group
      P2/a (No. 13), a=21.229(1) A, b=8.6451(5) A, c=25.762(2) A, beta=93.004(3)
      degrees, V=4721.6(5) A3, and Z=4.

PMID- 14658861
TI  - Energy density distribution in bridged cobalt complexes.
AB  - In the theory of atoms in molecules (AIM), the charge density is usually a
      suitable tool for bonding analyses. However, problems arise in some cases. So, no
      direct Co-Co bond is found in Co2(CO)8. It is shown that the energy density gives
      deeper insight into the bonding properties. This is demonstrated for Co2(CO)8,
      Co4(CO)12, and Co2(CO)6(InMe)2. The strategy is not restricted to transition
      metal compounds; it should be useful to identify any weak bonding or antibonding
      interactions.

PMID- 14658862
TI  - A ditopic azacryptate proton cage.
AB  - A tosylated azacryptand readily protonates at the bridgehead amines, becoming a
      potential ditopic anion receptor. The in-in conformation of the amines
      facilitates encapsulation of two bromide guests and represents the first
      structural evidence that a proton cage cryptate can bind two anions internally.

PMID- 14658863
TI  - A novel hybrid of Bi-based high-Tc superconductor and molecular complex.
AB  - Molecular complex HgI2Py2 (Py=pyridine) was intercalated into the Bi-based high
      Tc cuprate by intercalative complexation. The intercalation method adopted in
      this work is based on the new concept, where a neutral ligating agent is diffused
      into the preintercalated HgI2 layer leading to a charge transfer-type complex
      formation between the Bi2O2 double layers of Bi2Sr2CaCu2Oy.

PMID- 14658864
TI  - Synthesis of open and closed metallacages using novel tripodal ligands: unusually
      stable silver(I) inclusion compound.
AB  - The tripodal ligand 1,3,5-(CH3)3C6[CH2OCH2C(pz)3]3 (L1, pz=pyrazolyl ring) reacts
      with AgBF4 to yield ([L12Ag3(CH3CN)](BF4)3).(CH3CN)4, an inclusion complex in
      which the encapsulated acetonitrile cannot escape the triangular cage unit in
      either the solid or solution phase. The analogous hexatopic ligand
      C6[CH2OCH2C(pz)3]6 forms a 2-dimensional polymer composed of similar triangular
      cage units, again with the encapsulation of one acetonitrile molecule, linked by
      the additional tris(pyrazolyl)methane units. In contrast, the complex formed with
      L1 and Cd2+ has a double, open cage structure holding two diethyl ether
      molecules.

PMID- 14658865
TI  - The remarkable reactivity of high oxidation state ruthenium and osmium
      polypyridyl complexes.
AB  - There is a remarkable redox chemistry of higher oxidation state M(IV)-M(VI)
      polypyridyl complexes of Ru and Os. They are accessible by proton loss and
      formation of oxo or nitrido ligands, examples being cis-[RuIV(bpy)2(py)(O)]2+
      (RuIV=O2+, bpy=2,2'-bipyridine, and py=pyridine) and trans-[OsVI(tpy)(Cl)2(N)]+
      (tpy=2,2':6',2' '-terpyridine). Metal-oxo or metal-nitrido multiple bonding
      stabilizes the higher oxidation states and greatly influences reactivity. O-atom
      transfer, hydride transfer, epoxidation, C-H insertion, and proton-coupled
      electron-transfer mechanisms have been identified in the oxidation of organics by
      RuIV=O2+. The Ru-O multiple bond inhibits electron transfer and promotes complex
      mechanisms. Both O atoms can be used for O-atom transfer by trans
      [RuVI(tpy)(O)2(S)]2+ (S=CH3CN or H2O). Four-electron, four-proton oxidation of
      cis,cis-[(bpy)2(H2O)RuIII-O-RuIII(H2O)(bpy)2]4+ occurs to give cis,cis
      [(bpy)2(O)RuV-O-RuV(O)(bpy)2]4+ which rapidly evolves O2. Oxidation of NH3 in
      trans-[OsII(tpy)(Cl)2(NH3)] gives trans-[OsVI(tpy)(Cl)2(N)]+ through a series of
      one-electron intermediates. It and related nitrido complexes undergo formal N-
      transfer analogous to O-atom transfer by RuIV=O2+. With secondary amines, the
      products are the hydrazido complexes, cis- and trans-[OsV(L3)(Cl)2(NNR2)]+
      (L3=tpy or tpm and NR2-=morpholide, piperidide, or diethylamide). Reactions with
      aryl thiols and secondary phosphines give the analogous adducts cis- and trans
      [OsIV(tpy)(Cl)2(NS(H)(C6H4Me))]+ and fac-[OsIV(Tp)(Cl)2(NP(H)(Et2))]. In dry
      CH3CN, all have an extensive multiple oxidation state chemistry based on couples
      from Os(VI/V) to Os(III/II). In acidic solution, the OsIV adducts are protonated,
      e.g., trans-[OsIV(tpy)(Cl)2(N(H)N(CH2)4O)]+, and undergo proton-coupled electron
      transfer to quinone to give OsV, e.g., trans-[OsV(tpy)(Cl)2(NN(CH2)4O)]+ and
      hydroquinone. These reactions occur with giant H/D kinetic isotope effects of up
      to 421 based on O-H, N-H, S-H, or P-H bonds. Reaction with azide ion has provided
      the first example of the terminal N4(2-) ligand in mer
      [OsIV(bpy)(Cl)3(NalphaNbetaNgammaNdelta)]-. With CN-, the adduct mer
      [OsIV(bpy)(Cl)3(NCN)]- has an extensive, reversible redox chemistry and undergoes
      NCN(2-) transfer to PPh3 and olefins. Coordination to Os also promotes ligand
      based reactivity. The sulfoximido complex trans-[OsIV(tpy)(Cl)2(NS(O)-p-C6H4Me)]
      undergoes loss of O2 with added acid and O-atom transfer to trans-stilbene and
      PPh3. There is a reversible two-electron/two-proton, ligand-based
      acetonitrilo/imino couple in cis-[OsIV(tpy)(NCCH3)(Cl)(p-NSC6H4Me)]+. It
      undergoes reversible reactions with aldehydes and ketones to give the
      corresponding alcohols.

PMID- 14658866
TI  - Unusual geometries and questions of oxidation state in potential Sn(III)
      chemistry.
AB  - A mixed-valence compound (Sn2I3(NPPh3)3) with nonequivalent Sn atoms in
      characteristic 2+ and 4+ Sn geometries, raised the idea of an average Sn3+
      structure. The extended structures of Sr4Sn2Se9 and Sr4Sn2Se10 contain an unusual
      Sn2Se6 subunit, which has two equal Se-Sn-Se angles close to 160 degrees. This
      was suggestive of a Sn3+/Sn3+ compound, similar to the putative transition state
      for the valence state interchange in the molecular compound. These interesting
      geometrical features of two quite different molecules prompt a series of
      computations, a detective story of geometries and oxidation states, which
      concludes tentatively that the Sn with the abnormal angle in the extended
      structure is still likely to be formally Sn4+.

PMID- 14658868
TI  - Octalkoxy-substituted phosphorus(V) triazatetrabenzcorroles via ring contraction
      of phthalocyanine precursors.
AB  - As part of efforts toward developing the synthesis of novel corrole analogues,
      the new triazatetrabenzcorrole (TBC) phosphorus(V) compounds (BuO)8(TBC)P(OCH3)2
      (3), [(BuO)8(TBC)P(OH)]+OH- (4) ((BuO)8TBC=3,6,10,13,17,20,24,27
      octabutoxytriazatetrabenzcorrolate), and [(BuO)8Cl8(TBC)P(OH)]+OH- (7)
      ((BuO)8Cl8TBC=3,6,10,13,17,20,24,27-octabutoxy-4,5,11,12,18,19,25,26
      octachlorotriazatetrabenzcorrolate) were prepared. These TBCs were synthesized
      via a ring-contraction reaction mediated by PBr3 in pyridine in which a meso
      nitrogen atom is extruded from an appropriate phthalocyanine precursor. Two of
      the compounds prepared, 3 and 4, are contracted analogues of the parent
      phthalocyanine (BuO8)PcH2 (1) 1,4,8,11,15,18,22,25-octabutoxy-29H,31H
      phthalocyanine, which has been shown for the first time to be susceptible to ring
      contraction despite the potential steric crowding imposed by the butoxy
      substituents. Likewise, the octachloro-substituted (BuO8)Cl8PcH2 (6),
      1,4,8,11,15,18,22,25-octabutoxy-2,3,9,10,16,17,23,24-octachlorophthalocyanine,
      has also been shown to smoothly afford 7 via the same ring-contraction method. In
      addition, a rare example of a bona fide phosphorus(V) phthalocyanine,
      [(BuO)8(Pc)P(OCH3)2]+OH- (2), has been prepared for spectroscopic comparisons
      with the TBC compounds. These molecules are all extremely soluble in common
      organic solvents because of the octabutoxy substituents and have been
      characterized in detail by 1H NMR, 31P NMR, UV-vis, MALDI-MS, elemental analysis,
      and electrochemical studies. A clear trend in the phosphorus chemical shifts for
      5 versus 6 coordination has been delineated: 31P NMR for 2, -179.8; 3, -186.1; 4,
      -105.1; and 7, -105.1. These data are compared to the 31P chemical shifts for
      related porphyrinoid(P(V)) molecules. The MALDI-MS data reveal the tendency of
      the TBC macrocycles to ionize as the radical cations (M(+*)) and has been useful
      in determining the axial ligands at phosphorus. A consequence of ring-contraction
      is reflected in the dramatic red-shifts (approximately 200 nm) observed for the
      Soret bands of the TBC compounds relative to the parent phthalocyanines. The
      magnitude of the red-shift is much greater than that reported for other TBCs. In
      addition, insertion of phosphorus causes a large red-shift in the Q-band of 2
      found at 889 nm compared to 760 nm for 1. Cyclic voltammetry of the compounds in
      this study reveals multiple oxidation and reduction waves for each compound, and
      some interesting trends in redox potentials have been observed. The CV data for
      the octachloro-substituted compounds 6 and 7 show that the Cl substituents have
      an expected strong electron-withdrawing effect on the macrocycles. In general,
      the TBC compounds are significantly easier to oxidize and harder to reduce than
      the Pc counterparts, supporting the notion that corrole-type macrocycles favor
      higher oxidation states.

PMID- 14658867
TI  - A new class of oxo-bridged high-valent hexamanganese clusters supported by
      sterically hindered carboxylate ligands.
AB  - A new class of oxo-bridged high-valent hexamanganese (Mn6) clusters containing a
      novel (Mn6O8)6+ core, [MnIV(4)MnIII2(mu-O)4(mu3-O)4(dmb)6(O2CR)2]4+ (where
      dmb=4,4'-dimethyl-2,2'-bipyridine, and RCO2=2,6-di(p-tolyl)benzoate (Ar(Tol)CO2-)
      (3) or 2,6-di(4-tert-butylphenyl)benzoate (Ar(4-tBuPh)CO2-) (4)), was synthesized
      using sterically hindered m-terphenyl-derived carboxylate ligands. These
      complexes can be synthesized by oxidizing the MnII mononuclear complexes,
      [Mn(dmb)2(OH2)(O2CR)]+ (where RCO2=Ar(Tol)CO2- (1) or Ar(4-tBuPh)CO2- (2)) with
      (n-Bu4N)MnO4, by direct Mn(II) + Mn(VII) in situ comproportionation reactions, or
      by ligand substitution on the dinuclear manganese (III,IV) or (IV,IV) complexes,
      [(Mn2(mu-O)2(dmb)4)](3+/4+). The compound [MnIV4MnIII2(mu-O)4(mu3
      O)4(dmb)6(Ar(Tol)CO2)2](OTf)4 [3(OTf)4] crystallizes in the monoclinic space
      group P2(1)/n, with the cell parameters a=15.447(1) A, b=15.077(2) A, c=27.703(2)
      A, beta=91.68(2) degrees, V=6449.3(6) A3, and Z=2. The X-ray structure reveals
      that there are three different bridging modes for the oxo groups: mu, "pyramidal"
      mu3, and "T-shaped" mu3. Solid-state variable temperature magnetic susceptibility
      studies suggest that the Mn centers are net antiferromagnetically coupled to
      yield a diamagnetic ST=0 ground spin state with a large number of low-lying,
      thermally accessible states with ST>0. 1H NMR spectra were recorded for both Mn6
      clusters and selected resonances assigned. The electronic and redox properties of
      these complexes along with the effect of the presence of the bulky carboxylate
      ligands are also described here.

PMID- 14658869
TI  - Tetraphosphinitoresorcinarene complexes: cationic silver(I) and copper(I) halide
      complexes as mercurate(II) anion receptors.
AB  - The reactions of mercury(II) halides with the tetraphosphinitoresorcinarene
      complexes [P4M5X5], where M=Cu or Ag, X=Cl, Br, or I, and
      P4=(PhCH2CH2CHC6H2)4(O2CR)4(OPPh2)4 with R=C6H11, 4-C6H4Me, C4H3S, OCH2CCH, or
      OCH2Ph, have been studied. The reactions of the complexes with HgX2 when M=Ag and
      X=Cl or Br occur with elimination of silver(I) halide and formation of
      [P4Ag2X(HgX3)], but when M=Ag and X=I, the complexes [P4Ag4I5(HgI)] are formed.
      When M=Cu and X=I, the products were the remarkable capsule complexes
      [(P4Cu2I)2(Hg2X6)]. When M=Ag and X=I, the reaction with both CuI and HgI2 gave
      the complexes [P4Cu2I(Hg2I5)]. Many of these complexes are structurally
      characterized as containing mercurate anions weakly bonded to cationic
      tetraphosphinitoresorcinarene complexes of copper(I) or silver(I) in an unusual
      form of host-guest interaction. In contrast, the complex [P4Ag4I5(HgI)] is
      considered to be derived from an anionic silver cluster with an iodomercury(II)
      cation. Fluxionality of the complexes in solution is interpreted in terms of
      easy, reversible making and breaking of secondary bonds between the copper(I) or
      silver(I) cations and the mercurate anions.

PMID- 14658870
TI  - [Mn2(saltmen)2Ni(pao)2(L)2](A)2 with L=pyridine, 4-picoline, 4-tert
      butylpyridine, N-methylimidazole and A=ClO4-, BF4-, PF6-, ReO4-: a family of
      single-chain magnets.
AB  - A series of single-chain magnets, [Mn2(saltmen)2Ni(pao)2(L)2](A)2 (saltmen(2
      )=N,N'-(1,1,2,2-tetramethylethylene) bis(salicylideneiminate), pao-=pyridine-2
      aldoximate; A-=ClO4- with L=4-picoline; 2, 4-tert-butylpyridine; 3, N
      methylimidazole; 4, and L=pyridine with A-=BF4-; 5, PF6-; 6, ReO4-; 7), was
      prepared by reactions between MnIII dimer units, i.e., [Mn2(saltmen)2(H2O)2](A)2
      (A-=ClO4-, BF4-, PF6-) or Mn2(saltmen)2(ReO4)2, and NiII monomeric units, i.e.,
      Ni(pao)2(L)2, in methanol/water media. The crystal structures of 4, 6, and 7 were
      established by single-crystal X-ray crystallography. These three compounds are
      isostructural with [Mn2(saltmen)2Ni(pao)2(py)2](ClO4)2 (1) (Clerac, R.; Miyasaka,
      H.; Yamashita, M.; Coulon, C. J. Am. Chem. Soc. 2002, 124, 12837) and crystallize
      in monoclinic space group C2/c. The linear arrangement of MnIII dimer units and
      NiII building blocks leads to an alternating chain having a repeating unit, [
      (O)2-Mn-ON-Ni-NO-Mn-]. The chains are well separated with the nearest interchain
      intermetallic distance of 10.36 A for 4, 10.51 A for 6, and 10.30 A for 7, and
      there is no significant pi-pi interchain interaction between ligands. The void
      space between the chains is occupied by counteranions, which control the three
      dimensional organization of the chains. The X-ray diffraction analysis (XRD) on a
      powder sample was also performed for all compounds. The XRD patterns for 1, 2,
      and 4-7 are very similar, emphasizing the isostructural nature of these materials
      although they have individually slight different interchain distances. Inversely,
      the XRD pattern for 3 reveals a completely different shape being indicative of
      the peculiar crystal packing compared to the others. Nevertheless, the one
      dimensional nature of the structure is also kept in 3 as indicated by magnetic
      measurements. The whole family of compounds exhibits quasi-identical magnetic
      behavior compared to that described for 1. Above 30 K, the heterometallic chain
      can be described as an assembly of antiferromagnetically coupled Mn...Ni....Mn
      trimers (via oximate bridge, -24.2 K<J(Mn-Ni)/kB<-20.8 K) connected through
      Mn...Mn ferromagnetic interaction (via the phenolate bridge, J(Mn-Mn)/kB
      approximately +0.7 K), assuming a ferromagnetic chain with S=3 units. In the low
      temperature region, combined ac and dc magnetic measurements revealed for the
      whole series the systematic presence of a magnet behavior exhibiting coercivity
      and slow relaxation of magnetization below 3.5 K. This behavior was analyzed on
      the basis of Glauber's theory for an Ising one-dimensional system which predicts
      an activated dependence (Arrhenius law) of the relaxation time: tau=tau0
      exp(Delta/kBT). Similar values of tau0 approximately 1x10(-10) s and Delta/kB
      approximately 70 K have been found along the series. The described compounds
      constitute the first example of the rational design of a single-chain magnet
      family and clearly demonstrate the unique behavior of these heterometallic chains
      independently of their interchain environments.

PMID- 14658871
TI  - Cobalt(II) dioxygen carriers based on simple diamino ligands: kinetic and ab
      initio studies.
AB  - The kinetics of the oxygenation reaction of CoL2(2+) complexes (L=ethylenediamine
      (en), N,N'-dimethylethylenediamnine (dmen)) have been investigated in dimethyl
      sulfoxide (dmso) at 298 K and in a medium adjusted to 0.1 mol dm(-3) with
      Et4NClO4 by means of a UV-vis spectrophotometric technique. The reaction
      mechanisms are consistent with the fast formation of superoxo 1:1 initial CoL2-O2
      species (L=en, dmen), whereas the dimeric mu-peroxo (CoL2)2O2 adduct is formed
      only when L=en, in the rate determining step. The kinetic results are discussed
      taking into account the effects of ligand/solvent substitution. EPR results give
      information on the electronic structure and the coordination geometry of the
      Co(II) complexes and further confirm the stoichiometry of the species formed. Ab
      initio calculations provide insights on the geometrical parameters of all the
      complexes investigated and allow us to draw some hypotheses about the influence
      of H.H nonbonded interactions in the eventual formation of the dimeric mu-peroxo
      (CoL2)2O2 complexes. Solvational effects are also considered. The formation of
      the (CoL3)2O2 adduct is also proved when L=en by means of O2 volumetric
      absorption.

PMID- 14658872
TI  - "Nanoscale zippers" in Gd5(SixGe(1-x))4: symmetry and chemical influences on the
      nanoscale zipping action.
AB  - One critical parameter influencing the structural nature of the phase transitions
      in magnetocaloric materials Gd5(SixGe(1-x))4 is the Si/Ge ratio (x/1-x), because
      transition temperatures and structures depend crucially on this value. In this
      study, single-crystal X-ray diffraction indicates that Si and Ge atoms are
      neither completely ordered nor randomly mixed among the three crystallographic
      sites for these elements in these structures. Ge atoms enrich the T sites linking
      the characteristic slabs in these structures, while Si atoms enrich the T sites
      within them. Decomposition of the total energy into site and bond energy terms
      provides a rationale for the observed distribution, which can be explained by
      symmetry and electronegativity arguments. For any composition in Gd5(SixGe(1
      x))4, a structure map is presented that will allow for a rapid assessment of the
      specific structure type.

PMID- 14658873
TI  - Synthesis and mesogenic properties of binuclear copper(II) complexes derived from
      salicylaldimine Schiff bases.
AB  - The synthesis and mesomorphic (liquid crystal) properties of new binuclear
      dihalocopper(II) complexes derived from N- and ring-substituted salicylaldimine
      Schiff bases are reported, together with the mesomorphic properties of their
      monomeric precursor complexes. With just N-substituents both the
      dichlorodicopper(II) binuclear complexes and their mononuclear analogues are waxy
      solids with melting points that increase with their N-chain length. However, with
      both N- and ring-substituents in the 4-positions, the mononuclear and binuclear
      complexes are each liquid crystalline or mesogenic, except in case of the
      mononuclear complexes where the N-substituent is straight chain alkyl. The other
      mononuclear complexes exhibit a variety of liquid crystal phases: smectic A, C,
      and E (SA, SC, and SE, respectively). The liquid crystal phase SA is observed in
      the binuclears with shorter chain N-substituents p-R-O-C6H4- and shorter chain
      ring-substituents. The chain lengths were increased until the phase behavior
      expanded to a further form SC in the case of an N-substituent p-C14H29O-C6H4- and
      a -OC12H25 ring substituent. This points the way toward achieving multiphase
      behavior with these binuclear systems. The Cu-Br analogues of the binuclear
      complexes behave similarly but with significant qualitative differences,
      specifically lower mesophase stability and higher melting temperatures. The
      structures of the nonmesogenic binuclears ([Cu(N-dodecylSal)X]2, X=Cl, Br) were
      determined with the aid of X-ray crystallography. These are prototypes for the
      structures of the binuclear complexes and especially for the shape of the central
      Cu2O2 X2 core in the binuclears: distorted planar coordination about the copper
      with distortion toward tetrahedral measured by a characteristic twist angle tau
      (0 degrees planar; 90 degrees tetrahedral). The binuclear complexes also show
      magnetic coupling which can be used to estimate the geometry. For [Cu(N
      dodecylSal)X]2 tau>36 degrees, which corresponds to weaker coupling than observed
      in the mesogenic binuclears where a stronger magnetic coupling indicates a
      geometry closer to planar (tau=25 degrees). The mesophases were characterized by
      differential scanning calorimetry (DSC) analysis and optical polarized
      microscopy.

PMID- 14658874
TI  - One metal and forty nitrogens. Ab initio predictions for possible new high-energy
      pentazolides.
AB  - High-energy nitrogen-rich pentazolides of groups 6 and 13-16 are studied
      theoretically. Many of them have experimentally known azide analogues. Our
      highest nitrogen-to-element ratio of 40:1 is achieved in the systems [M(N5)8](2-)
      (M=Cr, Mo, W). The thermodynamic and kinetic stability of the studied systems
      grows with the negative charge on the system and is highest for tetra
      pentazolides and hexa-pentazolides of B, Al, and Si. Systems such as B(N5)4- or
      Si(N5)6(2-) are examples of the most stable candidates for these new species.
      N(N5)2- is a candidate for a new all-nitrogen system. Neutral and positive
      systems were less stable. Pentazole derivatives of "dinuclear" C2Hn and N2Hn
      systems were investigated and were found to be of comparable stability as their
      "mononuclear" analogues. Pentazole derivatives of benzene, the C6H(6-n)(N5)n
      (n=2, 3, 6) systems, have a similar stability as the experimentally known
      phenylpentazole. A borazine analogue, N3B3H3(N5)3 is predicted to be one of the
      most stable systems of this family.

PMID- 14658875
TI  - Coexistence of water dimer and hexamer clusters in 3D metal-organic framework
      structures of Ce(III) and Pr(III) with pyridine-2,6-dicarboxylic acid.
AB  - Ce(NO3)3.6H2O or Pr(NO3)3.6H2O and pyridine-2,6-dicarboxylic acid form a linear
      coordination polymeric structure under hydrothermal conditions. Hexameric water
      clusters join these linear chains through bonding to the metal ions. Other
      coordinated water and the carboxylate oxygen form an intricate array of hydrogen
      bonding resulting in a 3D network where each metal ion shows 9-coordination with
      an approximate D3 symmetry. Dimeric water clusters are also located in the void
      spaces. In the structure containing Pr(III), the water dimers are hydrogen-bonded
      to the hexamers, whereas in the Ce(III) structure, the dimers and the hexamers
      are far apart.

PMID- 14658876
TI  - Synthesis and structure of polymeric networks of silver hexafluoroacetylacetonate
      complexes of THF, toluene, and vinyltrimethylsilane.
AB  - The reaction of 1,1,1,5,5,5-hexafluoroacetylacetone (Hhfac) with Ag2O in the
      presence of L=THF, toluene, and Me3SiCH=CH2 was studied to obtain [Ag(hfac)L]x
      complexes for use as chemical vapor deposition precursors. The structures and
      volatilities of these three complexes were compared to those of the previously
      synthesized Ag(hfac)(Me3SiC triple bond CSiMe3), 1, which was also
      crystallographically characterized for comparison. The reaction of Ag2O with
      Hhfac in THF forms the polymeric complex [Ag4(hfac)4(THF)2]infinity, 2, which has
      tetrametallic subunits with hfac ligands that bridge via oxygen and carbon. Both
      4- and 5-coordinate silver metal centers are found in 2. Ag2O reacts with Hhfac
      in toluene to form a complex with a similar tetrametallic unit
      [Ag4(hfac)4(toluene)2]infinity, 3. In this case, the tetrametallic subunits are
      assembled via bridging toluene molecules, and each silver is 6-coordinate. In the
      presence of excess vinyltrimethylsilane (vtms), Ag2O and Hhfac form
      [Ag3(hfac)3(vtms)]infinity, 4, which contains trimetallic subunits assembled via
      oxygen atoms of bridging hfac ligands and 5- and 6-coordinate silver.

PMID- 14658877
TI  - The Pacman effect: a supramolecular strategy for controlling the excited-state
      dynamics of pillared cofacial bisporphyrins.
AB  - The molecular recognition properties of dizinc(II) bisporphyrin anchored by
      dibenzofuran (DPD), Zn2(DPD) (1), were evaluated as a strategy for utilizing the
      Pacman effect to control the excited-state properties of cofacial bisporphyrin
      motifs. Crystallographic studies establish that DPD furnishes a cofacial system
      with vertical flexibility and horizontal preorganization. The structure
      determination of a substrate-bound DPD species, Zn2(DPD)(2-aminopyrimidine) (2),
      completes a set of structurally homologous zinc(II) porphyrin host and host-guest
      complexes, which offer a direct structural comparison for the Pacman effect upon
      substrate complexation. Binding studies reveal that pyrimidine encapsulation by
      the DPD framework is accompanied by a markedly reduced entropic penalty
      (approximately 60 J mol(-1)K(-1)) with respect to traditional face-to-face
      bisporphyrin systems, giving rise to a smaller conformational energy cost upon
      substrate binding. Transient absorption spectroscopy reveals that substrate
      encapsulation within the DPD cleft dramatically affects excited-state dynamics of
      cofacial bisporphyrins. The emission lifetime of host-guest complex 2 increases
      by more than an order of magnitude compared to free host 1. In the absence of the
      guest, the excited-state dynamics are governed by torsional motion of the
      porphyrin rings about the aryl ring of the DPD pillar. Host-guest binding
      attenuates this conformational flexibility, thereby removing efficient
      nonradiative decay pathways. Taken together, these findings support the
      exceptional ability of the DPD system to structurally accommodate reaction
      intermediates during catalytic turnover and provide a novel supramolecular
      approach toward developing a reaction chemistry derived directly from the excited
      states of Pacman constructs.

PMID- 14658879
TI  - Electron deficiency in tetrahedral transition-metal clusters: electronic
      structure and magnetic properties of [Ru4(eta6-C6H6)4(mu3-H)4](2+).
AB  - Analysis of the electronic structure of the electron-deficient cluster cation
      [Ru4(eta6-C6H6)4H4](2+) (1(2+)) by density functional theory calculations shows a
      very small energy gap (0.06 eV) between the diamagnetic singlet state and the
      paramagnetic triplet state, as a consequence of the absence of a significant Jahn
      Teller distortion in the molecular structure of 1(2+). Magnetic measurements of
      [1]Cl2, [1][BF4]2, and [1][PF6]2 show 1(2+) to be diamagnetic in the fundamental
      state, with some weak temperature-independent paramagnetism, depending upon the
      nature of the counterion.

PMID- 14658878
TI  - Transient absorption studies of the Pacman effect in spring-loaded diiron(III) mu
      oxo bisporphyrins.
AB  - Picosecond transient absorption spectroscopy of diiron(III) mu-oxo bisporphyrins
      appended to xanthene, (DPX)Fe2O and (DPXM)Fe2O, and dibenzofuran (DPD)Fe2O have
      been investigated in order to decipher the effect of a spring-loaded cleft on
      their photophysics and attendant oxidation photocatalysis. The tension of the
      cofacial pocket is systematically tuned with the bridge span and meso
      substitution opposite to the bridge; the distances of the relaxed cofacial
      pockets and clamped Fe-O-Fe pockets are known from X-ray crystallography
      (Deltad(M-M)(relaxed-clamped)=4.271 A (DPD), 2.424 A (DPXM), 0.208 A (DPX)). The
      photophysical and chemical properties of these cofacial platforms are compared to
      the unbridged diiron(III) mu-oxo analogue, (Etio)2Fe2O. Photon absorption by the
      diiron(III) mu-oxo chromophore prompts Fe-O-Fe photocleavage to release the
      spring and present a PFeIVO/PFeII pair (P=porphyrin subunit); net photooxidation
      is observed when oxygen atom transfer to substrate occurs before the spring can
      reclamp to form the mu-oxo species. The inherent lifetimes of the PFeIVO/PFeII
      pairs for the four compounds are surprisingly similar (tau[(DPD)Fe2O]=1.36(3) ns,
      tau[(DPX)Fe2O]=1.26(5) ns, tau[(DPXM)Fe2O]=1.27(9) ns, and
      tau[(Etio)2Fe2O]=0.97(3) ns), considering the structural differences arising from
      tensely clamped (DPD and DPXM), relaxed (DPX), and unbridged (Etio) cofacial
      architectures. However, the rates of net oxygen atom transfer for (DPD)Fe2O and
      (Etio)2Fe2O are found to be 4 orders of magnitude greater than that of (DPX)Fe2O
      and 2 orders of magnitude greater than that of (DPXM)Fe2O. These results show
      that the spring action of the cleft, known as the Pacman effect, does little to
      impede reclamping to form the mu-oxo species but rather is manifest to opening
      the cofacial cleft to allow substrate access to the photogenerated oxidant.
      Consistent with this finding, photooxidation efficiencies decrease as the steric
      demand of substrates increase.

PMID- 14658880
TI  - Novel iron(III) complexes of tripodal and linear tetradentate bis(phenolate)
      ligands: close relevance to intradiol-cleaving catechol dioxygenases.
AB  - Four new iron(III) complexes of the bis(phenolate) ligands N,N-dimethyl-N',N'
      bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L1)], N,N-dimethyl-N',N'
      bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L2)], N,N'-dimethyl-N,N'-bis(2
      hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L3)], and N,N'-dimethyl-N,N'-bis(2
      hydroxy-4-nitrobenzyl)ethylenediamine [H2(L4)] have been isolated and studied as
      structural and functional models for the intradiol-cleaving catechol 1,2
      dioxygenases (CTD). The complexes [Fe(L1)Cl] (1), [Fe(L2)(H2O)Cl] (2), [Fe(L3)Cl]
      (3), and [Fe(L4)(H2O)Cl] (4) have been characterized using absorption spectral
      and electrochemical techniques. The single-crystal X-ray structures of the ligand
      H2(L1) and the complexes 1 and 2 have been successfully determined. The tripodal
      ligand H2(L1) containing a N2O2 donor set represents the metal-binding region of
      the iron proteins. Complex 1 contains an FeN2O2Cl chromophore with a novel
      trigonal bipyramidal coordination geometry. While two phenolate oxygens and an
      amine nitrogen constitute the trigonal plane, the other amine nitrogen and
      chloride ion are located in the axial positions. In contrast, 2 exhibits a
      rhombically distorted octahedral coordination geometry for the FeN2O3Cl
      chromophore. Two phenolate oxygen atoms, an amine nitrogen atom, and a water
      molecule are located on the corners of a square plane with the axial positions
      being occupied by the other nitrogen atom and chloride ion. The interaction of
      the complexes with a few monodentate bases and phenolates and differently
      substituted catechols have been investigated using absorption spectral and
      electrochemical methods. The effect of substituents on the phenolate rings on the
      electronic spectral features and FeIII/FeII redox potentials of the complexes are
      discussed. The interaction of the complexes with catecholate anions reveals
      changes in the phenolate to iron(III) charge-transfer band and also the
      appearance of a low-energy catecholate to iron(III) charge-transfer band similar
      to catechol dioxygenase-substrate complexes. The redox behavior of the 1:1
      adducts of the complexes with 3,5-di-tert-butylcatechol (H2DBC) has been also
      studied. The reactivities of the present complexes with H2DBC have been studied
      and illustrated. Interestingly, only 2 and 4 catalyze the intradiol-cleavage of
      H2DBC, the rate of oxygenation being much faster for 4. Also 2, but not 4, yields
      an extradiol cleavage product. The reactivity of the complexes could be
      illustrated not on the basis of the Lewis acidity of the complexes alone but by
      assuming that the product release is the rate-determining phase of the catalytic
      reaction.

PMID- 14658881
TI  - Self-assembly of a mixed-ligand metal-coordination polymeric network of
      cadmium(II) croconate with 4,4'-bipyridine.
AB  - A new cadmium croconate (C5O5(2-)) complex, [Cd2(C5O5)2(4,4'-bpy)(H2O)]infinity
      (4,4-bpy=4,4'-bipyridine) with an extended network has been synthesized under
      hydrothermal conditions and characterized by single-crystal X-ray diffraction
      studies. The title compound crystallizes in the monoclinic system, space group
      P2(1)/n, with empirical formula C20H12Cd2N2O12, a=15.9623(3) A, b=7.5837(1) A,
      c=18.1181(3) A, beta=99.95(2) degrees, and Z=4. Structural determination reveals
      that the title compound has a bilayered network, containing two
      crystallographically independent Cd(II) ions in different coordination
      environments. Cd(1) lies in a distorted pentagonal bipyramidal environment,
      consisting of three croconate ions and one 4,4'-bpy nitrogen donor, while Cd(2)
      lies in a distorted octahedral environment, consisting of two croconate anions,
      one 4,4'-bpy nitrogen donor, and one water molecule. Of the two crystallographic
      independent croconate ligands, one presents a bis-bidentate adjacent mu3
      coordination mode and the other a new bidentate/three-adjacent mu5-coordination
      mode. A two-dimensional hybrid layer is formed by two rectangular boxes as the
      building units through the connectivity between Cd(II) and croconate and 4,4'-bpy
      ligands.

PMID- 14658882
TI  - Magnetic property studies of manganese-phosphate complexes.
AB  - Phosphoric acid forms two distinct coordination compounds with manganese salts in
      aqueous media, a two-dimensional layered structure, [Mn(HPO4).(H2O)3], 1, under
      ambient conditions, and a three-dimensional synthetic mineral, [Mn5(mu
      OH2)2(HPO4)2(PO4)2(H2O)2], 2, under hydrothermal procedures, at 120 degrees C. In
      compound 1, the oxygen atom of the doubly deprotonated phosphoric acid
      interconnects the metal centers to form a layered structure. The neutral
      hydrophilic layers of 1 are separated by 5.5 A and may potentially intercalate
      hydrophilic organic guest molecules. The metal centers in 2 are octahedral and
      bridged by PO4(3-), HPO4(2-), and OH2 groups to form a complex three-dimensional
      network. XPS analysis on 1 and 2 confirms that manganese exists in the +2
      oxidation state. Compound 2 is a poor ion exchanger, but some improvement is
      observed on partial dehydration. The magnetic properties of both 1 and 2 were
      studied in detail to examine the amplitude of the magnetic interactions through
      phosphate ligand bridges. While 1 reveals dominant antiferromagnetic interactions
      between the spin carriers, a complete investigation of the magnetic properties of
      2 revealed its true nature to be a glassy magnet.

PMID- 14658883
TI  - Solvent effects on the electrochemistry and spectroelectrochemistry of
      diruthenium complexes. Studies of Ru2(L)4Cl where L=2-CH3ap, 2-Fap, and 2,4,6
      F3ap, and ap is the 2-anilinopyridinate anion.
AB  - Three Ru2(5+) diruthenium complexes, (4,0) Ru2(2-CH3ap)4Cl, (3,1) Ru2(2-Fap)4Cl,
      and (3,1) Ru2(2,4,6-F3ap)4Cl where ap is the 2-anilinopyridinate anion, were
      examined as to their electrochemical and spectroelectrochemical properties in
      five different nonaqueous solvents (CH2Cl2, THF, PhCN, DMF, and DMSO). Each
      compound undergoes a single one-electron metal-centered oxidation in THF, DMF,
      and DMSO and two one-electron metal-centered oxidations in CH2Cl2 and PhCN. The
      three diruthenium complexes also undergo two reductions in each solvent except
      for CH2Cl2, and these electrode processes are assigned as Ru2(5+/4+) and
      Ru2(4+/3+). Each neutral, singly reduced, and singly oxidized species was
      characterized by UV-vis thin-layer spectroelectrochemistry, and the data are
      discussed in terms of the most probable electronic configuration of the compound
      in solution. The three neutral complexes contain three unpaired electrons as
      indicated by magnetic susceptibility measurements using the Evans method (3.91
      3.95 muB), and the electronic configuration is assigned as
      sigma2pi4delta2pi(*2)delta, independent of the solvent. The three singly oxidized
      compounds have two unpaired electrons in CD2Cl2, DMSO-d6, or CD3CN (2.65-3.03
      muB), and the electronic configuration is here assigned as sigma2pi4delta2pi(*2).
      The singly reduced compound also has two unpaired electrons (2.70-2.80 muB) in
      all three solvents, consistent with the electronic configuration
      sigma2pi4delta2pi(*2)delta(*2) or sigma2pi4delta2pi(*3)delta*. Finally, the
      overall effect of solvent on the number of observed redox processes is discussed
      in terms of solvent binding, and several formation constants were calculated.

PMID- 14658884
TI  - A novel layered niobium oxychloride compound based on Nb2 pairs and Nb6
      octahedral clusters: synthesis and crystal and electronic structures of
      Nb10Cl16O7.
AB  - The synthesis, single crystal structure determination, and electronic structure
      of Nb10Cl16O7, the first Nb6 oxychloride stabilized without countercation, are
      reported in this work. The crystal structure is very original since it consists
      of layers built up from both Nb6 octahedral clusters and Nb2 pairs. The
      Nb6Oi6Cli6Cla6 and Nb2(mu2-Cl)2Cl4O4 units form [Nb6Cli6Oi4O(i-i)(2/2)Cl(a
      a)(4/2)Cla2]infinity infinite chains and [(Nb2(mu2-Cl)2O(2/2)Cl(4/2)O2)2]infinity
      double chains, respectively, that are interconnected by shared oxygen and
      chlorine ligands leading to layers. The cohesion of the three-dimensional
      structure (3D) is ensured by van der Waals contacts between layers that are
      randomly stacked along the [011] direction. Structural correlations between
      Nb10Cl16O7 and related Nb6 cluster oxyhalides, as well as NbOCl2 and NbCl4
      containing Nb2 pairs, are discussed. DFT results show that among the 20 valence
      electrons involved in the metal-metal bonding states, 14 electrons belong to the
      octahedral Nb6Cli6Oi6Cla6 unit whereas the 6 others (i.e., 1.5 per Nb atom)
      participate in the bonding in the distorted [(Nb2(mu2
      Cl)2O(2/2)Cl(4/2)O2)2]infinity double chains.

PMID- 14658885
TI  - Synthesis, crystal structure, magnetic properties, and theoretical studies of
      [(Cu(mepirizole)Br)2(mu-OH)(mu-pz)] (mepirizole=4-methoxy-2-(5-methoxy-3-methyl
      1H-pyrazol-1-yl)-6-methylpyrimidine; pz=pyrazolate), a novel mu-pyrazolato-mu
      hydroxo-dibridged copper(II) complex.
AB  - A novel mu-pyrazolato-mu-hydroxo-dibridged copper(II) complex has been
      synthesized and structurally characterized: [(Cu(mepirizole)Br)2(mu-OH)(mu-pz)]
      (mepirizole=4-methoxy-2-(5-methoxy-3-methyl-1H-pyrazol-1-yl)-6-methylpyrimidine;
      pz=pyrazolate). The title compound crystallizes in the monoclinic system, space
      group P2(1)/c, with a=15.618(2) A, b=15.369(3) A, c=16.071(3) A, and
      beta=112.250(1) degrees. The structure is built up of dinuclear
      [(Cu(mepirizole)Br)2(mu-OH)(mu-pz)] units with five-coordinated copper(II) ions
      (CuBrN3O chromophores) linked by mu2-OH and mu2-pyrazolato bridges that are well
      separated from each others. The intramolecular copper-copper distance is 3.378(3)
      A. Magnetic susceptibility data show that the copper atoms are strongly
      antiferromagnetically coupled with J=-770 cm(-1). The obtained triplet-singlet
      energy gap is compared with those reported for a series of related dimers. The
      strong antiferromagnetic coupling arising from the complementarity of the hydroxo
      and pyrazolato bridges has been discussed on the basis of DFT calculations.

PMID- 14658886
TI  - Silver(I) undecafluorodiantimonate(V).
AB  - The reaction between AgBF4 and excess of SbF5 in anhydrous hydrogen fluoride
      (aHF) yields the white solid AgSb2F11 after the solvent and the excess of SbF5
      have been pumped off. Reaction between equimolar amounts of AgSb2F11 and AgBF4
      yields AgSbF6. Meanwhile, oxidation of solvolyzed AgSb2F11 in aHF by elemental
      fluorine yields a clear blue solution of solvated Ag(II) cations and SbF6-
      anions. AgSb2F11 is orthorhombic, at 250 K, Pbca, with a=1091.80(7) pm,
      b=1246.28(8) pm, c=3880.2(3) pm, V=5.2797(6) nm3, and Z=24. The crystal structure
      of AgSb2F11 is related to the already known crystal structure of H3OSb2F11.
      Vibrational spectra of AgSb2F11 entirely match the literature-reported
      vibrational spectra of beta-Ag(SbF6)2, for which a formulation of a mixed-valence
      AgI/AgIII compound was suggested (AgIAgIII(SbF6)4). On the basis of obtained
      results it can be concluded that previously reported beta-Ag(SbF6)2 is in fact
      Ag(I) compound with composition AgSb2F11.

PMID- 14658887
TI  - Attempted syntheses of lanthanide(III) complexes of the anisole- and
      anilinosquarate ligands.
AB  - The polymeric lanthanide complexes (Ln(mu-CH3OC6H5C4O3)(CH3OC6H5C4O3)2
      (H2O)4.xH2O)n [Ln=La (1), Eu (2), Gd (3)], formed from the reaction of aqueous
      solutions of anisolesquarate and Ln(NO3)3.xH2O, are all structurally similar with
      only subtle differences between the lanthanum complex and the isomorphous pair of
      europium and gadolinium analogues. The lanthanum atom in 1 has a square
      antiprismatic coordination geometry comprising two pendant and two mu-1,3
      bridging anisolesquarate groups and four aqua ligands. Complexes 2 and 3 have two
      independent metal atoms in their asymmetric units compared to one for the
      lanthanum complex. However, the gross structures of 1-3 are essentially the same.
      The asymmetric unit of the terbium complex ((CH3OC6H5C4O3)3Tb(H2O)4(mu
      CH3OC6H5C4O3)(CH3OC6H5C4O3)2Tb(H2O)5).H2O (4) contains two independent binuclear
      units which hydrogen bond to form an extended structure very similar to those of
      1-3. The ionic polymers ([Ln(mu2-C4O4)(H2O)6][C6H5NHC4O3].4H2O)n [Ln=Eu (5), Gd
      (6), Tb (7)] result from the incomplete hydrolysis of the anilinosquarate ion
      during the attempted synthesis of Eu(III), Gd(III), and Tb(III) anilinosquarate
      complexes. However, complete hydrolysis of the substituent is accomplished by
      La(III) ions, and the neutral polymer (La2(mu2-C4O4)2(mu3-C4O4)(H2O)11.2H2O)n (8)
      is formed. In complexes 5-7, the central lanthanide atom has a square
      antiprismatic geometry, being bonded to two mu-1,2-bridging squarate and six aqua
      ligands. Two anilinosquarate counteranions participate in second-sphere
      coordination via direct hydrogen bonding to aqua ligands on each metal center.
      These counteranions, and the included waters of crystallization, serve to link
      neighboring cationic polymer chains via an extensive array of O-H...O hydrogen
      bonds to form a 3-dimensional network. The polymeric lanthanum complex 8 contains
      two different metal environments, each having distorted monocapped square
      antiprismatic geometry. For one lanthanum atom the coordination polyhedron
      comprises five aqua and four squarate ligands, while for the other the polyhedron
      consists of six aqua and three squarate ligands; in each case one of the aqua
      ligands occupies the capping position. The squarate ligand exhibits two
      coordination modes in 8 (mu-1,2- and mu-1,3-bridging), and neighboring polymer
      chains are cross-linked by hydrogen bonds to form a 3-dimensional network.

PMID- 14658889
TI  - Chemistry of cobalt acetate. 7. Electrochemical oxidation of mu3-oxo-centered
      cobalt(III) acetate trimers.
AB  - Electrochemical and spectroelectrochemical properties of five cobalt(III) acetate
      complexes [CoIII3(mu3-O)(CH3CO2)5(OR)(py)3][PF6] are described, where py=pyridine
      and R=OCCH3 (A), H (B), CH3 (C), CH2CH=CH2 (D), and CH2C6H5 (E). Each is reduced
      irreversibly as observed by cyclic voltammetry at room temperature and at -40
      degrees C in acetonitrile at scan rates up to 20 V s(-1), but oxidized reversibly
      to a mixed-valence Co(III)2Co(IV) species at approximately 1.23 V vs the
      ferrocenium/ferrocene couple. Controlled potential coulometry confirmed a one
      electron-oxidation process. Spectroelectrochemical oxidation of A at 5 degrees C
      showed isosbestic points in the electronic absorption spectrum that showed the
      oxidized complex to be stable in solution for at least 1 h.

PMID- 14658888
TI  - Phosphate diester hydrolysis and DNA damage promoted by new cis-aqua/hydroxy
      copper(II) complexes containing tridentate imidazole-rich ligands.
AB  - The tridentate Schiff base [(2-(imidazol-4-yl)ethyl)(1-methylimidazol-2
      yl)methyl)imine (HISMIMI) and its reduced form HISMIMA were synthesized and
      characterized, as well their mononuclear cis-dihalo copper(II) complexes 1 and 2,
      respectively. In addition, the dinuclear [CuII(mu-OH)2CuII](2+) complexes (3) and
      (4) obtained from complexes 1 and 2, respectively, were also isolated and
      characterized by several physicochemical techniques, including magnetochemistry,
      electrochemistry, and EPR and UV-vis spectroscopies. The crystal structures of 1
      and 2 were determined by X-ray crystallography and revealed two neutral complexes
      with their tridentate chelate ligands meridionally coordinated. Completing the
      coordination spheres of the square-pyramidal structures, a chloride ion occupies
      the apical position and another is bonded in the basal plane. In addition,
      complexes 1 and 2 were investigated by infrared, electronic, and EPR
      spectroscopies, cyclic voltammetry, and potentiometric equilibrium studies. The
      hydrolytic activity on phosphate diester cleavage of 1 and 2 was investigated
      utilizing 2,4-BDNPP as substrate. These experiments were carried out at 50
      degrees C, and the data treatment was based on the Michaelis-Menten approach,
      giving the following kinetic parameters (complex 1/complex 2): vmax (mol L(-1) s(
      1))=16.4x10(-9)/7.02x10(-9); KM (mol L(-1))=17.3x10(-3)/3.03x10(-3); kcat (s(
      1))=3.28x10(-4)/1.40x10(-4). Complex 1 effectively promoted the hydrolytic
      cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions,
      with a rate constant of 0.28 h(-1) for the decrease of form I, which represents
      about a 10(7) rate increase compared with the estimated uncatalyzed rate of
      hydrolysis.

PMID- 14658890
TI  - A new look at bonding in trialuminides: reinvestigation of TaAl3.
AB  - Single crystals of TaAl3 were grown at high temperatures from an Al-rich, binary
      solution. TaAl3 adopts the D0(22) structure type, space group I4/mmm with
      a=3.8412(5) A, c=8.5402(17) A, and Z=2. The structure type, which is the
      preferred structure for all group 5 trialuminides and TiAl3 as well as the high
      temperature form of HfAl3, is a binary coloring of the face-centered-cubic (fcc)
      arrangement. The distribution of Ta atoms creates a three-dimensional network of
      vertex and edge-sharing square pyramids of Al atoms. Temperature-dependent
      electrical resistivity and magnetic susceptibility measurements are consistent
      with TaAl3 being a metallic compound with a relatively low density of states at
      the Fermi surface. Furthermore, tight-binding electronic structure calculations
      are utilized to describe the bonding in these compounds and to compare their
      stability with respect to the alternative fcc-related, e.g., the D0(23) (ZrAl3
      type) and the L1(2) (AuCu3-type), structures. A modified Wade's rule argument
      provides insights into the structural preferences.

PMID- 14658891
TI  - Enhancement of luminescence lifetimes of mononuclear ruthenium(II)-terpyridine
      complexes by manipulation of the sigma-donor strength of ligands.
AB  - The synthesis and characterization of mixed ligand 2,2';6',2' '-terpyridine (tpy)
      ruthenium complexes with 2,6-bis([1,2,4]triazol-3-yl)pyridine, 2,6-bis(5-phenyl
      [1,2,4]triazol-3-yl)pyridine, and 2,6-bis([1,2,3,4]tetrazol-5-yl)pyridine are
      reported. The species are characterized by HPLC, 1H NMR, UV/vis, and emission
      spectroscopy. The photophysical properties of the complexes are investigated as a
      function of temperature over the range 80-320 K. The emission lifetime observed
      for the fully deprotonated compounds at room temperature is about 80 ns. This
      increase by 2 orders of magnitude with respect to the parent "[Ru(tpy)2](2+)"
      complex is rationalized by an increase in the energy of the metal based dsigma
      orbital, rather than by manipulation of the pi* orbitals on the ligands. The acid
      base and electrochemical properties of the compounds are reported also.

PMID- 14658892
TI  - Synthesis, structure, and acid-base and redox properties of a family of new
      Ru(II) isomeric complexes containing the trpy and the dinucleating Hbpp ligands.
AB  - Three pairs of mononuclear geometrical isomers containing the ligand 3,5-bis(2
      pyridyl)pyrazole (Hbpp) of general formula in- and out-[RuII(Hbpp)(trpy)X](n+)
      (trpy=2,2':6',2' '-terpyridine; X=Cl, n=1, 2a,b; X=H2O, n=2, 3a,b; X=py
      (pyridine), n=2, 4a,b) have been prepared through two different synthetic routes,
      isolated, and structurally characterized. The solid state structural
      characterization was performed by X-ray diffraction analysis of four complexes:
      2a-4a and 4b. The structural characterization in solution was performed by means
      of 1D and 2D NMR spectroscopy for complexes 2a,b and 4a,b and coincides with the
      structures found in the solid state. All complexes were also spectroscopically
      characterized by UV-vis which also allowed us to carry out spectrophotometric
      acid-base titrations. Thus, a number of species were spectroscopically
      characterized with the same oxidation state but with a different degree of
      protonation. As an example, for 3a three pKa values were obtained:
      pKa1(RuII)=2.13, pKa2(RuII)=6.88, and pKa3(RuII)=11.09. The redox properties were
      also studied, giving in all cases a number of electron transfers coupled to
      proton transfers. The pH dependency of the redox potentials allowed us to
      calculate the pKa of the complexes in the Ru(III) oxidation state. For complex
      3a, these were found to be pKa1(RuIII)=0.01, pKa2(RuIII)=2.78, and
      pKa3(RuIII)=5.43. The oxidation state Ru(IV) was only reached from the Ru-OH2
      type of complexes 3a or 3b. It has also been shown that the RuIV=O species
      derived from 3a is capable of electrocatalytically oxidizing benzyl alcohol with
      a second-order rate constant of kcat=17.1 M(-1) s(-1).

PMID- 14658893
TI  - Substituent effects of beta-diketiminate ligands on the structure and
      physicochemical properties of copper(II) complexes.
AB  - Substituent effects of beta-diketiminate ligands on the structure and
      physicochemical properties of the copper(II) complexes have been systematically
      investigated by using 3-iminopropenylamine derivatives R1LR3H, R3-N=CH-C(R1)=CH
      NH-R3, where R1 is Me, H, CN, or NO2, and R3 is Ph, Mes (mesityl), Dep (2,6
      diethylphenyl), Dipp (2,6-diisopropylphenyl), or Dtbp (3,5-di-tert-butylphenyl).
      When the ligands with R3=Ph or Dtbp were treated with CuII(OAc)2, bis(beta
      diketiminate) copper(II) complexes exhibiting distorted tetrahedral geometries
      were obtained, the crystal structures of which were nearly the same as each other
      regardless of the alpha-substituent (R1); dihedral angles between the two beta
      diketiminate coordination planes are 62.5 +/- 1.2 degrees, and the Cu-N bond
      lengths are 1.959 +/- 0.008 A. The distorted tetrahedral structures are
      maintained in solution, but the spectroscopic features, especially gII values of
      the ESR spectra and the d-d bands of the absorption spectra, as well as the
      electrochemical behaviors of the complexes, are significantly affected by the
      electronic nature of R1. The ligands with R3=Mes and Dep, on the other hand, gave
      di(mu-hydroxo)dicopper(II) complexes, and their crystal structures as well as
      spectroscopic and electrochemical features have also been explored. Furthermore,
      the ligand with the more sterically encumbered aromatic substituent (Dipp)
      provided a mononuclear four-coordinate square planar copper(II) complex supported
      by one beta-diketiminate ligand and one didentate acetate ion. Thus, the beta
      diketiminate ligands with a variety of substituents (R1 and R3) have been
      explored to provide coordinatively unsaturated (four-coordinate) mononuclear and
      dinuclear copper(II) complexes with significantly different coordination geometry
      and properties.

PMID- 14658894
TI  - Interlayer interaction of two-dimensional layered spin crossover complexes
      [FeIIH3L(Me)][FeIIL(Me)]X (X-=ClO4-, BF4-, PF6-, AsF6-, and SbF6-; H3L(Me)=tris[2
      (((2-methylimidazol-4-yl)methylidene)amino)ethyl]amine).
AB  - A series of two-dimensional (2D) spin crossover complexes,
      [FeIIH3L(Me)][FeIIL(Me)]X (X-=ClO4-, BF4-, PF6-, AsF6-, SbF6-) 1-5, have been
      synthesized, where H3L(Me) denotes an hexadentate N6 tripodlike ligand containing
      three imidazole groups, tris[2-(((2-methylimidazol-4
      yl)methylidene)amino)ethyl]amine. Compounds 1-5 exhibit a two-step (HS
      [FeIIH3L(Me)](2+) + HS-[FeIIL(Me)]-) <--> (HS-[FeIIH3L(Me)](2+) + LS-[FeIIL(Me)]
      ) <--> (LS-[FeIIH3L(Me)](2+) + LS-[FeIIL(Me)]-) spin-transition. The crystal
      structure of [FeIIH3L(Me)][FeIIL(Me)]PF6 (3) was determined at 295, 200, and 100
      K. The structure consists of homochiral extended 2D puckered sheets, in which the
      complementary [FeIIH3L(Me)](2+) and [FeIIL(Me)]- capped tripodlike components,
      linked together by imidazole-imidazolate hydrogen bonds, are alternately arrayed
      in an up-and-down mode. The Fe-N bond distances and angles revealed that the FeII
      sites of both constituting units are in the high-spin (HS) state at 295 K; at 200
      K, the FeII sites of [FeIIH3L(Me)](2+) and [FeIIL(Me)]- are in the HS and low
      spin (LS) states, respectively. The FeII sites of both constituting units are in
      the LS state at 100 K. The size of the counteranion affects significantly the
      intra- and interlayer interactions leading to modifications of the spin crossover
      behavior. The onset of the second spin-transition of the ClO4- (1) and BF4- (2)
      salts adjoins the first spin-transition, while a mixed (HS-[FeIIH3L(Me)](2+) + LS
      [FeIIL(Me)]-) spin-state spans a temperature range as wide as 70 K for salts 3-5
      with larger counteranions, PF6-, AsF6-, and SbF6-, respectively. Compounds 1 and
      2 showed remarkable LIESST (light induced excited spin state trapping) and
      reverse-LIESST effects, whereas 3-5 showed no remarkable LIESST effect. The
      interlayer interaction due to the size of the counteranion is an important factor
      governing the spin crossover behavior and LIESST effect.

PMID- 14658895
TI  - Bridging fluorides and hard/soft mismatch in d6 and d8 complexes: the case of
      [Tl(mu-F)3Ru(PPh3)3].
AB  - [RuCl2(PPh3)3] reacts with thallium(I) fluoride to give either [Tl(mu
      F)3Ru(PPh3)3] (1) or [Tl(mu3-F)(mu2-Cl)2Ru2(mu2-Cl)(mu2-F)(PPh3)4] (2) depending
      on the excess of TlF used. Both 1 and 2 were fully characterized, including X-ray
      structure determinations. Complex 1 reacts with dihydrogen to form the known
      ruthenium hydride complex [Ru(H)2(H2)(PPh3)3] upon hydrogenolysis of the Ru-F
      bond. The reaction of 1 with activated alkyl bromides (R-Br) gives the
      corresponding alkyl fluorides and the trinuclear complex [Tl(mu3-F)(mu2-F)(mu2
      X)Ru2(mu2-Br)(mu2-F)(PPh3)4] (X=Br, F) (3), whose structure closely resembles
      that of 2. However, 1 is not active as catalyst for the nucleophilic fluorination
      of R-Br in the presence of thallium fluoride. The effect of the bridging
      coordination mode of fluoride on the Ru-F bond is discussed in terms of the HSAB
      principle, which suggests a more general model for predicting the stability of d6
      and d8 complexes containing hard ligands (such as fluoro, oxo, and amido).

PMID- 14658896
TI  - Luminescent gold(I) and silver(I) complexes of 2-(diphenylphosphino)-1
      methylimidazole (dpim): characterization of a three-coordinate Au(I)-Ag(I) dimer
      with a short metal-metal separation.
AB  - The Au(I) and Ag(I) closed-shell metal dimers of 2-(diphenylphosphino)-1
      methylimidazole, dpim, were investigated. dpim formed the discreet binuclear
      species [Ag2(dpim)2(CH3CN)2](2+) (1) when reacted with appropriate Ag(I) salts.
      Likewise, [Au2(dpim)2](2+) (3) and [AuAg(dpim)3](2+) (4) were produced via
      reactions with (tht)AuCl, tht is tetrahydrothiophene, and Ag(I). Compound 3
      exhibits an intense blue luminescence (lambdamax=483 nm) in the solid state.
      However, upon initial formation of 3, a small impurity of Cl- was present giving
      rise to an orange emission (lambdamax=548 nm). Attempts to form [Au2(dpim)2]Cl2
      yielded only (dpim)AuCl (2), which is not visibly emissive. The rare three
      coordinate heterobimetallic complex [AuAg(dpim)3](2+) (4) exhibits intense
      luminescence in the solid-state resembling that of 3. The crystal structures of 1
      4 were determined, revealing strong intramolecular aurophilic and argentophilic
      interactions in the dimeric compounds. Compound 1 has an Ag(I)-Ag(I) separation
      of 2.9932(9) A, while compound 3 has a Au(I)-Au(I) separation of 2.8174(10) A.
      Compound 4 represents the first example of a three-coordinate Au(I)-Ag(I) dimer
      and has a metal-metal separation of 2.8635(15) A. The linear Au(I) monomer, 2,
      has no intermolecular Au(I)-Au(I) interactions, with the closest separation
      greater than 6.8 A.

PMID- 14658897
TI  - Equilibrium studies in solution involving nickel(II) complexes of flexidentate
      Schiff base ligands: isolation and structural characterization of the planar red
      and octahedral green species involved in the equilibrium.
AB  - Three new flexidentate 5-substituted salicylaldimino Schiff base ligands (L1-OH
      L3-OH) based on 1-(2-aminoethyl)piperazine (X=H, L1-OH; X=NO2, L2-OH; and X=Br,
      L3-OH) and their nickel(II) complexes (1a, 1b, 2, and 3) have been reported. The
      piperazinyl arm of these ligands can in principle have both boat and chair
      conformations that allow the ligands to bind the Ni(II) center in an ambidentate
      manner, forming square-planar and/or octahedral complexes. The nature of
      substitution in the salicylaldehyde aromatic ring and the type of associated
      anion in the complexes have profound influences on the coordination geometry of
      the isolated products. With the parent ligand L1-OH, the product obtained is
      either a planar red compound [Ni(L1-O)]+, isolated as tetraphenylborate salt
      (1a), or an octahedral green compound [Ni(L1-NH)(H2O)3](2+), isolated with
      sulfate anion (1b); both have been crystallographically characterized. In aqueous
      solution, both these planar (S=0) and octahedral (S=1) forms are in equilibrium
      that has been followed in the temperature range 298-338 K by 1H NMR technique
      using the protocol of Evans's method. The large exothermicity of the equilibrium
      process [Ni(L1-O)]+ + 3H2O + H+<=>[Ni(L1-NH)(H2O)3](2+) (DeltaH degrees=-46 +/-
      0.2 kJ mol(-1) and DeltaS degrees=-133 +/- 5 J K(-1) mol(-1)) reflects formation
      of three new Ni-OH2 bonds in going from planar to the octahedral species. With
      the 5-nitro derivative ligand L2-OH, the sole product is an octahedral compound
      2, isolated as a sulfate salt while with the bromo derivative ligand L3-OH, the
      exclusive product is a planar molecule 3 with associated tetraphenylborate anion.
      Both 2 and 3 have been structurally characterized by X-ray diffraction analysis.

PMID- 14658898
TI  - Preparations of pure ISeCN, ISCN, and INCO.
AB  - Pure INCO, ISCN, and the hitherto unknown molecule ISeCN have been prepared in
      the HeI photoelectron spectrometer (PES) by the heterogeneous reactions of ICl
      gas with AgNCO, AgSCN at room temperature, and AgSeCN at -9 (+/- 1) degrees C,
      respectively. They were characterized on line by PES experiments and OVGF
      calculations. The well-matched results between the PES experiments and OVGF
      calculations not only show that the new reaction is a good reaction to prepare
      pure INCO and pure ISCN, but also that the new compound prepared by passing the
      ICl gas over the freshly AgSeCN powder at -9 (+/- 1) degrees C is the hitherto
      unknown ISeCN.

PMID- 14658899
TI  - Theoretical studies of the complex [(BPMEN)Fe(II)(NCCH3)2](2+), precursor of non
      heme iron catalysts for olefin epoxidation and cis-dihydroxylation.
AB  - The density functional theory (DFT) was applied to elucidate the electronic
      structure of the BPMEN [N,N'-bis(6-R-2-pyridylmethyl)-1,2-diaminoethane] iron
      complex, [(BPMEN)Fe(NCCH3)2](2+), a precursor of catalysts that catalyze the
      stereospecific olefin oxidation. The low-lying high and low spin states of
      complex 1 (R=H) are nearly degenerate with a slight preference for the high spin
      state. For complexes with substituents (R) at the 6-positions of two pyridine
      rings of BPMEN, the ground state is the high spin (HS) state, with the low spin
      (LS) state higher in energy by 9.5, 5.3, 8.5, 6.3, and 5.1 kcal/mol for complexes
      2 (R=CH3), 3 (R=SiH3), 4 (R=OH), 5 (R=F), and 6 (R=CN), respectively, with the
      B3LYP method. Our findings for complexes 1 and 2 are in good agreement with the
      experimental observations. The calculated LS-HS difference of 17.9 kcal/mol for
      complex 7 (R=t-Bu) clearly demonstrates that the steric effect causes the Fe-N
      bonds to stretch and favors the high spin state. Comparison of the B3LYP and
      B3PW91 results with experiments and ab initio MP2 and CCSD(T) as well as pure DFT
      results shows that hybrid DFT methods provide a qualitatively correct description
      of the relative energies of low-lying electronic states of a model of the
      [(BPMEN)Fe(NCCH3)2](2+) complex, while pure DFT methods underestimate the
      stability of the HS state.

PMID- 14658900
TI  - Structural and magnetic properties of three one-dimensional azido-bridged
      copper(II) and manganese(II) coordination polymers.
AB  - Three one-dimensional (1D) azido-bridged coordination polymers of formula
      [Cu(L)(N3)2]n (1), [Cu2(Me-L)(N3)4]n (2), and [Mn(L)(N3)2]n (3) have been
      synthesized and structurally characterized, and their magnetic properties
      studied, where L and Me-L are 2-(pyrazol-1-ylmethyl)pyridine and 2-(3
      methylpyrazol-1-ylmethyl)pyridine, respectively. Compound 1 consists of 1D chains
      in which the Cu(II) ions with a square pyramidal geometry are alternately bridged
      by an end-to-end (EE) and an end-on (EO) azido ligands, both adopting a basal
      apical disposition. Compound 2 exhibits an unprecedented chain topology built via
      three different kinds of EO azido bridges. Four Cu(II) ions in the square
      pyramidal environment are alternately bridged by single and double EO bridges to
      form a tetranuclear cyclic ring, and neighboring rings are interlinked by double
      EO bridges to generate a "chain of rings". The intraannular double azido ions are
      disposed between metal ions in a basal-basal fashion, and the other two kinds of
      azido ions adopt the basal-apical disposition. Compound 3 consists of 1D concave
      convex chains in which cis-octahedrally coordinated Mn(II) ions are alternately
      bridged by double EE and double EO bridges. There exist pi-pi interactions
      between the ligands bound to the neighboring Mn(II) ions bridged by the EO
      bridges. Temperature- and field-dependent magnetic analyses reveal alternate
      ferromagnetic interactions for 1, dominating ferromagnetic interactions for 2,
      and alternating ferro- and antiferromagnetic interactions through the EO and EE
      azido bridges for 3, respectively.

PMID- 14658901
TI  - New dicationic porphyrin ligands suited for intercalation into B-form DNA.
AB  - This paper describes the synthesis and characterization of a new series of
      sterically nondemanding, dicationic porphyrins that exhibit novel DNA-binding
      interactions. Cationic porphyrins continue to be the focus of a great deal of
      effort because of the promise they have for use in photodynamic, antiviral, and
      anticancer therapies. The systems explored here include 5,15-di(N
      methylpyridinium-4-yl)porphyrin (H2D4), 5,15-di(N-methylpyridinium-3-yl)porphyrin
      (H2D3), and 5,15-di(N-methylpyridinium-2-yl)porphyrin (H2D2), as well as Zn(D4)
      and Zn(D3), the zinc(II)-containing derivatives of H2D4 and H2D3, respectively.
      Viscometry studies, in conjunction with various spectroscopic techniques, reveal
      the nature of the adducts formed with DNA. Irrespective of the base composition,
      H2D4 and H2D3 bind to DNA by intercalation. The zinc derivatives Zn(D4) and
      Zn(D3) are also intercalators; however, the binding constants are smaller because
      uptake requires the loss of an axial ligand. The decisive roles that steric
      factors and structural rigidity play in shaping the adducts with DNA become
      clear. Sequences that contain mainly adenine-thymine base pairs easily depart
      from the canonical B-form DNA structure and generally accommodate bulky
      porphyrins in external binding sites. However, with the H2D3 and H2D4 systems,
      the steric requirements are so minimal that intercalation becomes the preferred
      mode of binding, even in [poly(dA-dT)]2. The intercalated form of the H2D2 isomer
      is less stable, probably because of frontal strain associated with the (N
      methyl)pyridinium-2-yl groups. A qualitative energy-level diagram is useful for
      assessing the forces that influence binding and could guide the design of new
      porphyrin ligands.

PMID- 14658902
TI  - Lanthanide-transition metal chalcogenido cluster materials.
AB  - [(THF)3Sm(SePh)2Zn(SePh)2]n decomposes to give a variety of products, including
      [(THF)8Sm4Se(SePh)8](2+)[Zn8Se(SePh)16](2-), an ionic cluster that can also be
      prepared in more than 60% yield by stoichiometric addition of Se to a mixture of
      Sm(SePh)3 and Zn(SePh)2. The isostructural Nd compound
      [(THF)8Nd4Se(SePh)8](2+)[Zn8Se(SePh)16](2-) was also prepared by the
      stoichiometric route to establish the viability of this cluster type with redox
      inactive Ln. In addition, the salt [Yb(THF)6](3+)[Fe4Se4(SePh)4](3-) was isolated
      and structurally characterized. These ionic cluster materials illustrate the
      difficulties associated with doping Ln ions into covalent metal chalcogenido
      matrixes.

PMID- 14658903
TI  - Interpolymetallic assembly of d8-d10 sulfide aggregates from [Pt2(PPh3)4(mu-S)2]
      and group 12 metals.
AB  - A series of heterometallic Pt-M (M=Zn and Cd) sulfide aggregates with growing
      nuclearities (Pt2M), (Pt4M), and (Pt4M2), viz., [ZnPt2Cl2(PPh3)4(mu3-S)2] (2),
      [CdPt2Cl2(PPh3)4(mu3-S)2] (3), [Pt2(PPh3)4(mu3-S)2]2[ZnSO4]2 (4), [Pt2(PPh3)4(mu3
      S)2]2[CdSO4]2.H2O (5), [CdPt4(PPh3)8(mu3-S)4][ClO4]2 (7), and [ZnPt4(PPh3)8(mu3
      S)4][ClO4]2 (8), have been prepared from Pt2(PPh3)4(mu-S)2 (1) with appropriate
      zinc and cadmium substrates. The structures have been determined by single
      crystal X-ray diffraction. The supporting anions play an active role in the
      structural assembly process. An unexpected disintegration complex
      [Pt2(S2CH2)Cl(PPh3)4][PF6] (6) has also been isolated and characterized by single
      crystal X-ray diffraction. The mechanism of the formation of 6 is proposed.

PMID- 14658904
TI  - Interaction of nitrogen oxides with sublimed layers of (meso
      tetraphenylporphyrinato)cobalt(II); IR evidence of oxo-transfer from
      (nitro)porphyrinatocobalt(III) to free nitric oxide.
AB  - Interaction of a low-pressure NO2 with sublimed layers of (meso
      tetraphenylporphyrinato)cobalt(II) (Co(TPP)) leads to formation of 5-coordinate
      nitro complex Co(III)(TPP)(NO2). Upon exposure of these layers to pyridine
      vapors, the fast reaction with formation of 6-coordinate nitro-pyridine
      porphyrins (Py)Co(III)(TPP)(NO2) occurs. By means of IR spectroscopy and use of
      nitrogen oxide isotopomers, it is shown that an oxo-transfer reaction occurs from
      5-coordinate species to free nitric oxide (NO) while the 6-coordinate complex is
      rather inert. It is also demonstrated that the stepwise addition of low-pressure
      NO2 to nitrosyl complex Co(TPP)(NO) leads to formation of the nitro complex most
      likely by an exchange reaction.

PMID- 14658905
TI  - Increased reactivity of the *Cr(CO)3(C5Me5) radical with thiones versus thiols: a
      theoretical and experimental investigation.
AB  - 2-pyridinethione (2-mercaptopyridine, H-2mp) undergoes rapid oxidative addition
      with 2 mol of the 17-electron organometallic radical *Cr(CO)3Cp (where
      Cp*=C5Me5), yielding hydride H-Cr(CO)3Cp* and thiolate (eta1-2mp)Cr(CO)3Cp*. In a
      slower secondary reaction, (eta1-2mp)Cr(CO)3Cp* loses CO generating the N,S
      chelate complex (eta2-2mp)Cr(CO)2Cp* for which the crystal structure is reported.
      The rate of 2-pyridine thione oxidative addition with *Cr(CO)3Cp* (abbreviated
      *Cr) in toluene best fits rate=kobs[H-2mp][*Cr]; kobs(288 K)=22 +/- 4 M(-1) s(
      1); DeltaH++=4 +/- 1 kcal/mol; DeltaS++=- 40 +/- 5 cal/mol K. The rate of
      reaction is the same under CO or Ar, and the reaction of deuterated 2-pyridine
      thione (D-2mp) shows a negligible (inverse) kinetic isotope effect (kD/kH=1.06 +/
      0.10). The rate of decarbonylation of (eta1-2mp)Cr(CO)3Cp* forming (eta2
      2mp)Cr(CO)2Cp* obeys simple first-order kinetics with kobs (288 K)=3.1x10(-4) s(
      1), DeltaH++=23 +/- 1 kcal/mol, and DeltaS++=+ 5.0 +/- 2 cal/mol K. Reaction of 4
      pyridine thione (4-mercaptopyridine, H-4mp) with *Cr(CO)3Cp* in THF and CH2Cl2
      also follows second-order kinetics and is approximately 2-5 times faster than H
      2mp in the same solvents. The relatively rapid nature of the thione versus thiol
      reactions is attributed to differences in the proposed 19-electron intermediate
      complexes, [*(S=C5H4N-H)Cr(CO)3Cp*] versus [*(H-S-C6H5)Cr(CO)3Cp*]. In
      comparison, reactions of pyridyl disulfides occur by a mechanism similar to that
      followed by aryl disulfides involving direct attack of the sulfur-sulfur bond by
      the metal radical. Calorimetric data indicate Cr-SR bond strengths for aryl and
      pyridyl derivatives are similar. The experimental conclusions are supported by
      B3LYP/6-311+G(3df,2p) calculations, which also provide additional insight into
      the reaction pathways open to the thione/thiol tautomers. For example, the
      reaction between H* radical and the 2-pyridine thione S atom yielding a thionyl
      radical is exothermic by approximately 30 kcal/mol. In contrast, the thiuranyl
      radical formed from the addition of H* to the 2-pyridine thiol S atom is
      predicted to be unstable, eliminating either H* or HS* without barrier.

PMID- 14658906
TI  - High-field, multifrequency EPR study of the [Mn(OH2)6](3+) cation: influence of
      pi-bonding on the ground state zero-field-splitting parameters.
AB  - High-field, multifrequency EPR data are presented for the alum CsMn(SO4)2.12D2O,
      containing the [Mn(OD2)6](3+) cation. The data are interpreted using the
      conventional S=2 spin Hamiltonian, and the following parameters determined for
      the data obtained below 30 K: D=-4.491(7) cm(-1), E=0.248(5) cm(-1), gx=1.981(5),
      gy=1.993(5), gz=1.988(5). Although the deviation of the MnO6 framework from
      idealized D(4h) symmetry is small, the magnitude of E/D is significant. The E
      parameter is related to ligand field parameters derived from the optical
      absorption spectrum. The rhombic anisotropy is shown to arise as a consequence of
      the pi-anisotropic nature of the manganese(III)-water interaction.

PMID- 14658907
TI  - Reactivity of Ph2P(Se)CH2C6H4CH2P(Se)Ph2 with [M3(CO)12] (M=Ru or Fe). Synthesis
      and characterization of the new carbene cluster [Ru3(mu3-Se)(mu3-H)(mu2
      PPh2)(CO)6(mu2-CHC6H4CH2PPh2)].
AB  - The reactions of [M3(CO)12] (M=Ru or Fe) with 1,2
      bis[(diphenylphosphino)methyl]benzene diselenide (dpmbSe2) in hot toluene afford
      a variety of phosphine-substituted selenido carbonyl clusters. They belong to the
      following three families: (i) 50-electron clusters with a M3Se2 core (2, 3, 5-7),
      (ii) 48-electron clusters with a M3Se core (1, 8), (iii) 34-electron clusters
      with a M2Se2 core (4). All these species derive from the P=Se bond cleavage.
      Cluster 1, which contains a hydrido, a phosphido, and a carbene ligand, is
      produced by multiple fragmentation of the diphosphine. This fragmentation appears
      related to the presence of the selenido ligand on the cluster, as the reaction of
      [Ru3(CO)12] with dpmb (not selenized) produces only carbonyl substitution by the
      phosphine to give [Ru3(CO)10(mu-dpmb)] (9). All the clusters synthesized have
      been characterized by spectroscopic techniques, and in some cases fluxional
      behavior has been detected in solution by NMR analysis. The structures of 1, 2,
      and 7-9 have been determined by X-ray diffraction methods.

PMID- 14658908
TI  - A new type of single-helix coordination polymer with mixed ligands [M2(phen)2(e,a
      cis-1,4-chdc)2(H2O)2]n (M=Co and Ni; phen=1,10-phenanthroline;
      chdc=cyclohexanedicarboxylate).
AB  - A new family of single-stranded helices coordination polymers with mixed ligands,
      [M2(phen)2(e,a-cis-1,4-chdc)2(H2O)2]n (1, M=Co; 2, M=Ni;
      chdc=cyclohexanedicarboxylic acid; phen=1,10-phenanthroline), were prepared under
      hydrothermal conditions and characterized by elemental analyses, IR spectra, TG
      analysis, and single-crystal X-ray diffraction analysis. X-ray crystal structural
      analyses reveal that 1 and 2 are isomorphic and belong to the monoclinic system.
      C40H36Co2N4O10, P2(1)/c, a=10.0566(5) A, b=8.8843(5) A, c=20.2912(14) A,
      beta=100.052(3) degrees, Z=2 for 1; and C40H36Ni2N4O10, P2(1)/c, a=9.8921(6) A,
      b=9.0151(4) A, c=20.1628(17) A, beta=100.31(2) degrees, Z=2 for 2. In the
      structures of 1 and 2, the 1,4-chdc ligand possesses only one kind of e,a-cis
      conformation although there are both cis- and trans-conformations in the raw
      material. Two oxygen atoms of one carboxyl in 1,4-chdc ligand and another oxygen
      atom of contraposition carboxyl link adjacent Co or Ni atoms into an infinite 1-D
      zigzag chain. The most attractive structural feature of 1 and 2 is that they both
      exhibit an infinite chiral chainlike structure with 2(1) helices along the b
      axis. In addition, the right-handed and the left-handed chains are alternate.
      Meanwhile, the adjacent chains of 1 and 2 are linked via hydrogen bonds into 2-D
      network structures, which further form 3-D frameworks via pi-pi interactions of
      1,10-phen.

PMID- 14658909
TI  - Low-temperature single-crystal Raman and neutron-diffraction study of the
      hydrogenous ammonium copper(II) Tutton salt and the deuterated analogue in the
      metastable state.
AB  - Low-temperature (15 K) single-crystal neutron-diffraction structures and Raman
      spectra of the salts (NX4)2[Cu(OX2)6](SO4)2, where X=H or D, are reported. This
      study is concerned with the origin of the structural phase change that is known
      to occur upon deuteration. Data for the deuterated salt were measured in the
      metastable state, achieved by application of 500 bar of hydrostatic pressure at
      approximately 303 K followed by cooling to 281 K and the subsequent release of
      pressure. This allows for the direct comparison between the hydrogenous and
      deuterated salts, in the same modification, at ambient pressure and low
      temperature. The Raman spectra provide no intimation of any significant change in
      the intermolecular bonding. Furthermore, structural differences are few, the
      largest being for the long Cu-O bond, which is 2.2834(5) and 2.2802(4) A for the
      hydrogenous and the deuterated salts, respectively. Calorimetric data for the
      deuterated salt are also presented, providing an estimate of 0.17(2) kJ/mol for
      the enthalpy difference between the two structural forms at 295.8(5) K. The
      structural data suggest that substitution of hydrogen for deuterium gives rise to
      changes in the hydrogen-bonding interactions that result in a slightly reduced
      force field about the copper(II) center. The small structural differences suggest
      different relative stabilities for the hydrogenous and deuterated salts, which
      may be sufficient to stabilize the hydrogenous salt in the anomalous structural
      form.

PMID- 14658910
TI  - Ligand effect on reversible conversion between copper(I) and bis(mu
      oxo)dicopper(III) complex with a sterically hindered tetradentate tripodal ligand
      and monooxygenase activity of bis(mu-oxo)dicopper(III) complex.
AB  - A new sterically hindered tetradentate tripodal ligand (Me2-etpy) and its labeled
      analogue having deuterated methylene groups (d4-Me2-etpy) were synthesized, where
      Me2-etpy is bis(6-methyl-2-pyridylmethyl)(2-pyridylethyl)amine. Copper(I)
      complexes [Cu(Me2-etpy or d4-Me2-etpy)]+ (1 and 1-d4, respectively) reacted with
      dioxygen at -80 degrees C in acetone to give bis(mu-oxo)dicopper(III) complexes
      [Cu2(O)2(Me2-etpy or d4-Me2-etpy)2](2+) (1-oxo and 1-d4-oxo, respectively), the
      latter of which was crystallographically characterized. Unlike a bis(mu
      oxo)dicopper(III) complex with a closely related Me2-tpa ligand having a 2
      pyridylmethyl pendant, 1-oxo possessing a 2-pyridylethyl pendant is not fully
      formed even under 1 atm of O2 at -80 degrees C and is very reactive toward the
      oxidation of the supporting ligand. Thermal decomposition of 1-oxo gave an N
      dealkylated ligand in yield approximately 80% based on a dimer and a
      corresponding aldehyde. The deuterated ligand d4-Me2-etpy greatly stabilizes the
      bis(mu-oxo)dicopper(III) complex 1-d4-oxo, indicating that the rate determining
      step of the N-dealkylation is the C-H bond cleavage from the methylene group. The
      reversible conversion between 1-d4 and 1-d4-oxo in acetone is dependent on the
      temperature, and the thermodynamic parameters (DeltaH and DeltaS) of the
      equilibrium were determined to be -53 +/- 2 kJ mol(-1) and -187 +/- 10 J mol(-1)
      K(-1), respectively. The effect of the 2-pyridylethyl pendant in comparison with
      the 2-pyridylmethyl and 6-methyl-2-pyridylmethyl pendants on the physicochemical
      properties of the copper(I) and bis(mu-oxo)dicopper(III) species is discussed.

PMID- 14658911
TI  - Systematic evaluation of molecular recognition phenomena. 3. Selective
      diphosphate binding to isomeric hexaazamacrocyclic ligands containing xylylic
      spacers.
AB  - The crystal structure of 3,7,11,18,22,26
      hexaazatricyclo[26.2.2.2(13,16)]tetratriaconta-1(31),13(34),14,16(33),28(32),29
      hexaene hexahydrobromide salt [(H6P3)Br6] has been determined by means of X-ray
      diffraction analysis. It crystallizes with an additional molecule of ethanol and
      half a molecule of water per molecule of the hydrobromide P3 ligand. The
      protonation constants of P3 and its host-guest interactions with monophospate
      (Ph) and pyrophosphate (Pp) have been investigated by potentiometric equilibrium
      methods. Ternary complexes are formed in aqueous solution as a result of hydrogen
      bond formation and Coulombic interactions between the host and the guest;
      formation constants for all the species obtained are reported and compared with
      the isomeric 3,7,11,19,23,27-hexaazatricyclo[27.3.1.1(13,17)]tetratriaconta
      1(33),13, 15,17(34),29,31-hexaene (Bn) ligand. For the H6P3Pp(2+) those bonding
      interactions reach a maximum yielding a log KR6 of 5.87. The selectivity of the
      P3 ligand with regard to the monophosphate and pyrophosphate substrates (S) is
      discussed and illustrated with global species distribution diagrams showing a
      strong preference for the latter over the former as a consequence of the much
      stronger formation constants with pyrophosphate. An analysis of the isomeric
      effect is also carried out by comparing the P3-S versus Bn-S systems. In the best
      case, a selectivity of over 88% is achieved for the diphosphate complexation when
      using the meta isomer over the para, due solely to the size and shape of the
      receptors cavity.

PMID- 14658912
TI  - Ligand substitution in cubic clusters: surprising isolation of the
      cocrystallization products of Cu8(mu8-Se)[S2P(OEt)2]6 and Cu6[S2P(OEt)2]6.
AB  - The cluster (Cu8(mu8-Se)[S2P(OEt)2]6)0.54(Cu6[S2P(OEt)2]6)0.46 (2) was prepared
      in 78% yield from the reaction of Cu8(Se)[Se2P(OPr)2]6 (1) and NH4S2P(OEt)2 in
      toluene. The central selenide ion in 2 was characterized by 77Se NMR at delta 
      976 ppm. The simulated solid-state 31P NMR spectrum shows two components with an
      intensity ratio close to 55:45. The peak centered at 100.7 ppm is assigned to the
      31P nuclei in the hexanuclear copper cluster, and that at 101.1 ppm is due to the
      octanuclear copper cluster. The single-crystal X-ray diffraction analysis
      confirms the cocrystallization structures of Cu8(Se)[S2P(OEt)2]6 (54%) and
      Cu6[S2P(OEt)2]6 (46%) (2: trigonal, space group R3, a=21.0139(13) A, c=11.404(3)
      A, gamma=120 degrees, Z=3). While the octanuclear copper cluster possesses a 3
      fold crystallographic axis which pass through the Cu2, Se, and Cu(2A) atoms, the
      six copper atoms having the S6 point group symmetry in Cu6[S2P(OEt)2]6 form a
      compressed octahedron. The Cu8(mu8-Se) cubic core in Cu8(mu8-Se)[S2P(OEt)2]6 is
      larger in size than the metal core in Cu8(mu8-Se)[Se2P(OPr)2]6 (1) although the
      bite distance of the Se-containing bridging ligand is larger than that of the S
      ligand. To understand the nature of the structure contraction of the metal core
      and metal-mu8-Se interaction, molecular orbital calculations have been carried
      out at the B3LYP level of density functional theory. MO calculations suggest that
      Cu-mu8-Se interactions are not very strong and a half bond can be formally
      assigned to each Cu-mu8-Se bond. Moderate Cu...Cu repulsion exists, and it is the
      bridging ligands that are responsible for the observed Cu...Cu contacts. Hence,
      the S-ligating copper clusters have greater Cu...Cu separations because each Cu
      carries more positive charge in the presence of the more electronegative S
      containing ligands.

PMID- 14658913
TI  - XAFS studies of anti-inflammatory dinuclear and mononuclear Zn(II) complexes of
      indomethacin.
AB  - Zinc K-edge X-ray absorption fine structure (XAFS) experiments were performed in
      the solid and solution states at low temperature (10 K), on dimeric and monomeric
      anti-inflammatory Zn(II) complexes of indomethacin [1-(4-chlorobenzoyl)-5-methoxy
      2-methyl-1H-indole-3-acetic acid=IndoH] of the formula [Zn2(Indo)4L2] [L=pyridine
      (Py), N,N-dimethylacetamide (DMA)], [Zn(Indo)2L2] [L=ethanol (EtOH), methanol
      (MeOH)], and Zn(II) acetate dihydrate [Zn(OAc)2(OH2)2]. The bond distances and
      angles obtained from multiple-scattering fits to the XAFS data of the Zn(II)
      dimeric complexes in the solid and solution states exhibit excellent
      correspondence with those obtained from single crystal diffraction studies. The
      Zn...Zn separations of 2.97 and 2.96 A and carboxylate group O-C-O angles of 125
      degrees for powdered [Zn2(Indo)4(Py)2] and [Zn2(Indo)4(DMA)2] agree well with the
      XRD values of 2.969(1) and 2.9686(6) A and 125.8(4) degrees and 126.1(2) degrees,
      respectively. The calculated Zn-O(RCOO) and Zn-L bond distances of 2.03 and 2.04
      A, or 2.02 and 1.98 A for Py or DMA complexes, respectively, also agree well with
      crystallographic data. The X-ray powder diffraction data on samples of the
      monomers exhibited additional reflections apart from those due to the
      crystallographically characterized cis-[Zn(eta2-O,O'-Indo)2L2], but microanalyses
      were consistent with this formulation. Therefore, mixed models that contained the
      cis complex and a second component consisting of a trans-six-coordinate complex,
      a five-coordinate complex, or a four-coordinate complex were used to model the
      XAFS. The best fits to the XAFS data were obtained with a mixture of the cis-six
      coordinate complex and a four-coordinate complex containing two monodentate Indo
      ligands. The bond lengths for the six-coordinate structure were consistent with
      those determined on a single crystal, and those for the four-coordinate complexes
      were consistent with related four-coordinate structures with two monodentate
      carboxylate ligands. Dissolution of the dimer (DMA adduct) in DMF resulted in a
      mixture of dimer and monomer species as shown by MS XAFS fitting. This is the
      first time that solution structures have been determined for anti-inflammatory
      Zn(II) complexes, and this is an important first step in understanding the
      pharmacology of the complexes.

PMID- 14658914
TI  - Synthesis and characterization of transition-metal Zintl phases: Cs24Nb2In12As18
      and Cs13Nb2In6As10 with isolated complex anions.
AB  - The title compounds were prepared by direct reaction of the corresponding
      elements at high temperature. Their structures were determined by single-crystal
      X-ray diffraction (Cs24Nb2In12As18, triclinic, P1, Z=1, a=9.519(4), b=9.540(5),
      and c=25.16(1) A, alpha=86.87(4), beta=87.20(4), and gamma=63.81(4) degrees;
      Cs13Nb2In6As10, triclinic, P1, Z=1, a=9.5564(5), b=9.6288(5), and c=13.9071(7) A,
      alpha=83.7911(8), beta=80.2973(8), and gamma=64.9796(8) degrees). Cs24Nb2In12As18
      and Cs13Nb2In6As10 contain isolated anions of [Nb2In12As18](24-) and
      [Nb2In6As10](13-), respectively. Each anion includes two cubane-like units made
      of one niobium, three indium, and four arsenic corners where a fifth arsenic atom
      completes the tetrahedral coordination at niobium, [(NbAs)In3As4]. In
      Cs13Nb2In6As10 these two units are connected via a direct In-In bond between two
      indium vertexes of the cubanes. In Cs24Nb2In12As18, on the other hand, the same
      two units are linked by a dimer made of semicubanes of [In3As4], i.e., a cubane
      with one missing vertex. Magnetic measurements show that Cs24Nb2In12As18 is
      diamagnetic, i.e., a d0 transition-metal Zintl phase, while Cs13Nb2In6As10
      exhibits a Curie-Weiss behavior that corresponds to one unpaired electron.

PMID- 14658915
TI  - Short-range and long-range magnetic ordering in SrCuP2O7 and PbCuP2O7.
AB  - Magnetic properties of SrCuP2O7 and PbCu(1-x)ZnxP2O7 (x=0, 0.1, and 0.5) were
      studied by magnetic susceptibility, chiT, and specific heat, Cp(T). Both data
      showed that magnetism of SrCuP2O7 and PbCuP2O7 can be described by the one
      dimensional (1D) uniform chain model despite the structural features suggesting
      the presence of zigzag chains with next-nearest-neighbor interactions. The chiT
      data were fitted by the Bonner-Fisher curve (plus temperature independent and
      Curie-Weiss terms) with g=2.20 and J/kB=9.38 K for SrCuP2O7 and g=2.17 and
      J/kB=8.41 K for PbCuP2O7 (Hamiltonian H=J SigmaSiS(i+1)). Magnetic specific heat,
      Cm(T), exhibited one broad maximum due to short-range ordering and one sharp peak
      at TN=1.64 K for SrCuP2O7 and TN=1.15 K for PbCuP2O7 due to long-range
      antiferromagnetic ordering. The characteristic values of the broad maxima on the
      Cm(T) curves (Cmax and TC(max)) were in good agreement with the theoretical
      calculations for the uniform 1D S=1/2 Heisenberg chain. Magnetic properties of
      PbCu0.9Zn0.1P2O7 still obeyed the 1D uniform chain model but those of
      PbCu0.5Zn0.5P2O7 did not. In air, SrCuP2O7 was stable at least up to 1373 K while
      PbCuP2O7 melted incongruently above 1180 K.

PMID- 14658916
TI  - Dinuclear and octanuclear Mn(II) complexes with mu2-C, mu2-N(pyrrolide), and mu
      eta1:eta5-(pyrrolide) bridges: a structural and magnetic study.
AB  - Reaction of the dinuclear [(CH2SiMe3)(mu-CH2SiMe3)Mn(THF)]2 (1) with an
      equivalent amount of 1,1-dipyrrolylcyclohexane afforded two compounds depending
      on the solvent employed. Reaction carried out in THF afforded the dinuclear ([1,1
      (mu-C4H3N)(C4H3N)C6H10]Mn(THF)2)2.2(THF) (2) while reaction in toluene yielded
      the octanuclear and cyclic cluster ([1,1-(mu,eta1:eta5
      C4H3N)2C6H10]Mn)8.4(toluene) (3). The magnetism in all three cases is dominated
      by intramolecular antiferromagnetic exchange with strong coupling in 1 (J=-85 cm(
      1)), and in 2 (J=-23.2 cm(-1)), whereas substantially weaker coupling through the
      sigma/pi-bonded dipyrrolide bridges (J=-3.3 cm(-1)) was observed within the
      cyclic and octameric 3.

PMID- 14658917
TI  - Synthesis, characterization, and hydrolytic behavior of mixed-ligand diorganotin
      esters, [R2Sn(O2CR')OSO2Me]2 (R=n-Pr, n-Bu; R'=C9H6N-2, 4-OMe-C9H5N-2, C9H6N-1).
AB  - Reactions of the tin precursors, R2Sn(OMe)OSO2Me (R=n-Pr, n-Bu), with an
      equimolar quantity of 2-quinoline/4-methoxy-2-quinoline/1-isoquinoline carboxylic
      acid in acetonitrile proceed under mild conditions (rt,12-15 h) via selective Sn
      OMe bond cleavage to afford the corresponding mixed-ligand diorganotin
      derivatives [R2Sn(O2CR')OSO2Me]2 [R'=C9H6N-2, R=n-Pr (1), n-Bu (2); R'=4-OMe
      C9H5N-2, R=n-Pr (3), n-Bu (4); R'=C9H6N-1, R=n-Pr (5), n-Bu (6)]. These have been
      characterized by FAB mass, IR, and multinuclear (1H, 13C, 119Sn) NMR spectral
      data and X-ray crystallography (for 4 and 6). The molecular structure of 4
      (C20H29NO6SSn, monoclinic, P2(1)/n, a=14.1(13) A, b=16.7(18) A, c=20.3(19) A,
      beta=107(4) degrees, Z=8) comprises distorted octahedral geometry around each tin
      atom by virtue of weakly bridging methanesulfonate [Sn(1A)-O(3B)=3.010, Sn(1B)
      O(3A)=2.984 A] and (N,O) chelation of the carboxylate ligands. The spectral data
      of 1-4 suggest a similar structural motif in solution. The molecular structure of
      6 (C38H53N2O10S2Sn2, monoclinic, P2(1)/c, a=11.339(2) A, b=14.806(3) A,
      c=24.929(5) A, beta=100.537(3) degrees, Z=4) reveals varying bonding preferences
      with monomeric units being held together by a bridging methanesulfonate [Sn(2)
      O(5)=2.312(2) A] and a carboxylate group bonded to Sn(1) and Sn(2) atoms,
      respectively. Slow hydrolysis of compound 2 derived from 2-quinoline carboxylic
      acid in moist CH3CN affords the asymmetric distannoxane, [Bu2Sn(O2CC9H6N-2)-O
      Sn(OSO2Me)Bu2]2 (7) (C27H45NO6SSn2, monoclinic, C2/c, a=21.152(3) A, b=13.307(2)
      A, c=26.060(4) A, beta=110.02(10) degrees, Z=8) featuring ladder type structural
      motif by virtue of unique mu2-coordination of covalently bonded oxygen atoms
      [O(6), O(6)#1] of the methanesulfonate groups.

PMID- 14658918
TI  - Blue dimetallic complexes of two heavy metal ions Cd(II) and Hg(II) with an
      extended nitrogen donor ligand. Preparation, spectral characterization, and
      crystallographic studies.
AB  - In methanol, the metal salts CdCl2.H2O and HgCl2 react instantaneously with the
      deprotonated ligand, L-, producing molecular dimetallic ink-blue complexes of
      general formula M2Cl2L2, M=Cd(II), (1) and Hg(II), (2) (HL=2-[2
      (pyridylamino)phenylazo]pyridine). Crystal structures of these two complexes are
      reported. The coordination sphere around each Cd(II) ion in 1 is a distorted
      square pyramidal. The metal ion (Cd1) sits above the basal plane of three
      nitrogen atoms, N(1), N(3), and N(4). The second cadmium ion (Cd2) in this
      compound lies below the plane of three nitrogen atoms, N(6), N(8), and N(9). The
      apical positions are occupied by two Cl atoms. Secondary intramolecular
      interactions between the metal ions and the anionic secondary amine nitrogen
      atoms (N(4) and N(9)) are noted. The geometry of each Hg(II) ion in the mercury
      complex, Hg2Cl2L2.0.5H2O, is also distorted square based pyramid with the metal
      ions lying out of planes of the three nitrogen atoms of the chelating ligands.
      Secondary Hg(1)...N(1A) (deprotonated amine) interactions are noted. The
      separation between the two Hg(II) ions in this complex is within the sum of their
      van der Waals radii. Solution properties of these blue complexes are reported.
      The origin of the intense blue color in these complexes is the intraligand
      transitions that occur near 615 nm. 1H NMR of Hg2Cl2L2.0.5H2O indicates that it
      undergoes exchange in solution with the coordinated ligands.

PMID- 14658920
TI  - Long-term use of stimulants in children with attention deficit hyperactivity
      disorder: safety, efficacy, and long-term outcome.
AB  - The purpose of this review is to summarize existing data on the long-term safety
      and efficacy of stimulant treatment, and how long-term stimulant treatment of
      children with attention deficit hyperactivity disorder (ADHD) affects their
      outcome. Existing controlled studies of children with ADHD treated and untreated
      with stimulants, as well as long-term prospective follow-up studies, are
      reviewed. Children with ADHD treated with stimulants for as long as 2 years
      continue to benefit from the treatment, with improvements observed in ADHD
      symptoms, comorbid oppositional defiant disorder, and academic and social
      functioning, with no significant problems of tolerance or adverse effects. Long
      term, prospective follow-up studies into adulthood show that stimulant treatment
      in childhood has slight benefits regarding social skills and self-esteem. Long
      term adverse effects from stimulant treatment in childhood regarding adult height
      or future substance abuse have not been supported by existing studies.

PMID- 14658921
TI  - Refractory idiopathic immune thrombocytopenic purpura in children: current and
      future treatment options.
AB  - A minority of children with idiopathic or immune thrombocytopenic purpura (ITP)
      have the refractory chronic form with bleeding problems (stage III or IV). The
      aim of this article is to provide an update on the immunopathogenesis and
      management of children with bleeding and severe refractory ITP. The management of
      such patients, according to a staging guideline, is described. Recent clinical
      and laboratory observations document the disturbed immune responses that occur on
      various levels in chronic ITP. New therapeutic options are directed towards
      influencing these immunopathogenic mechanisms. Because ITP is not adequately
      defined and has heterogeneous manifestations, today's management recommendations
      are largely opinion-based rather than evidence-based. In severe refractory
      childhood ITP, consensus between the treating physician and the patient has to be
      achieved on an individual basis. The aim is to maintain the disease at stages I
      or II, with minimal intervention, and to prevent bleeding. If bleeding is not
      under control, medical treatment (as described in this article), or splenectomy,
      has to be considered.Although there is a paucity of data relating to children,
      potential new treatment options for refractory ITP include strategies aimed at
      influencing antigenemia, the T cell immune response (e.g. cyclosporine, CTLA-4
      Ig) or the B-cell immune response (e.g. anti-CD20 monoclonal antibody, anti-CD52
      monoclonal antibody, interferon). New prospective, cooperative ITP registries
      have been created to search for subgroups with different severities of ITP, which
      will be the selection criteria of future controlled studies in pediatric patients
      with refractory ITP.

PMID- 14658923
TI  - Community-acquired pneumonia in children: issues in optimizing antibacterial
      treatment.
AB  - The treatment of community-acquired pneumonia (CAP) in children is empirical,
      being based on the knowledge of the etiology of CAP at different ages. As a
      result of currently available methods in everyday clinical practice, a microbe
      specific diagnosis is not realistic in the majority of patients. Even the
      differentiation between viral, 'atypical' bacterial (Mycoplasma pneumoniae or
      Chlamydia pneumoniae) and 'typical' bacterial (Streptococcus pneumoniae) CAP is
      often not possible. Moreover, up to one-third of CAP cases seem to be mixed viral
      bacterial or dual bacterial infections. Recent serologic studies have confirmed
      that S. pneumoniae is an important causative agent of CAP at all ages. M.
      pneumoniae is common from the age of 5 years onwards, and C. pneumoniae is common
      from the age of 10 years onwards. In addition to age, the etiology and treatment
      of CAP are dependent on the severity of the disease. Pneumococcal infections are
      predominant in children treated in hospital, and mycoplasmal infections are
      predominant in children treated at home.In ambulatory patients with CAP,
      amoxicillin (or penicillin V [phenoxymethylpenicillin]) is the drug of choice
      from the age of 4 months to 4 years, and at all ages if S. pneumoniae is the
      presumptive causative organism. Macrolides, preferably clarithromycin or
      azithromycin, are the first-line drugs from the age of 5 years onwards. In
      hospitalized patients who need parenteral therapy for CAP, cefuroxime (or
      penicillin G [benzylpenicillin]) is the drug of choice. Macrolides should be
      administered concomitantly if M. pneumoniae or C. pneumoniae infection is
      suspected. Radiologic findings and C-reactive protein (CRP) levels offer limited
      help for the selection of antibacterials; alveolar infiltrations and high CRP
      levels indicate pneumococcal pneumonia, but the lack of these findings does not
      rule out bacterial CAP. Most guidelines recommend antibacterials for 7-10 days
      (except azithromycin, which has a recommended treatment duration of 5 days). If
      no improvement takes place within 2 days, therapy must be reviewed.

PMID- 14658922
TI  - Anticoagulation therapy in children.
AB  - Thromboembolic disease (TED) is increasingly recognized as a major cause of
      morbidity and mortality in tertiary pediatrics. Children younger than 1 year of
      age and teenage girls are at greatest risk of thromboembolism. Although
      anticoagulation therapy is the treatment of choice for TED, the treatment
      strategy is often difficult, especially in children. Treatment relies largely on
      anticoagulation with heparin and warfarin. Recommendations for antithrombotic
      therapy in children have been loosely extrapolated from recommendations for
      adults; however, it is likely that optimal treatment of children with TED differs
      from adults because of important ontogenic features of hemostasis that affect
      both the pathophysiology of the thrombotic processes and the response to
      antithrombotic agents. Until recently, the primary treatment for TED has been
      unfractionated heparin (UFH) in conjunction with warfarin. Warfarin, the most
      commonly used oral anticoagulant, acts through inhibition of the vitamin K
      dependent transcarboxylation reactions that convert precursors of clotting
      factors into their active form. Appropriate use of UFH and warfarin requires
      close patient monitoring and dosage adjustments to ensure tolerability and
      efficacy. In recent years, low molecular weight heparins (LMWH) have become
      available as alternatives to UFH and warfarin, for both the prevention and
      treatment of TED. Potentially, LMWH have significant advantages. They have
      superior pharmacokinetics, which results in minimal laboratory monitoring,
      offering important benefits to children with poor venous access. Based on
      available data, LMWHs are at least as effective and well tolerated as UFH, and
      are more convenient. Although LMWHs are more expensive than UFH, the expense is
      likely to be offset by savings from a reduced hospital stay.

PMID- 14658924
TI  - Efficacy and safety of Ritalin LA, a new, once daily, extended-release dosage
      form of methylphenidate, in children with attention deficit hyperactivity
      disorder.
AB  - OBJECTIVE: To evaluate the safety and efficacy of extended-release
      methylphenidate with a bimodal profile using SODAS technology (Ritalin LA )
      compared with placebo in children aged 6-14 years with attention deficit
      hyperactivity disorder (ADHD). METHOD: This was a multicenter, double-blind,
      randomized, placebo-controlled, parallel-group study in children meeting
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for ADHD.
      Following titration and a 1-week placebo washout period, patients were randomized
      to 2 weeks of double-blind treatment with either Ritalin LA (10-40 mg/day) or
      placebo. The efficacy assessments used were the Conners' ADHD/DSM-IV Scales for
      teachers (CADS-T) and for parents (CADS-P), and the Clinical Global Impression
      Improvement Scale (CGI-I) completed by the investigator. The primary efficacy
      variable was the change from baseline (end of placebo washout) to the final
      rating (end of 2-week double-blind treatment) in the CADS-T Total subscale score.
      RESULTS: One-hundred-and-sixty-one children were treated and 134 responders were
      included in the intent-to-treat analysis. Ritalin LA achieved a mean change from
      baseline (+/- SD) on the CADS-T Total subscale of -10.7 (+/-15.68) compared with
      2.8 (+/-10.59) for placebo (p < 0.0001); the effect size on the CADS-T Total
      score with Ritalin LA was 0.90. Additionally, 69.8% of patients in the Ritalin LA
      group were rated as much or very much improved on the CGI-I at final assessment
      compared with 40% of patients in the placebo group (p = 0.0009). The adverse
      events reported were generally mild or moderate, and were similar in both groups.
      CONCLUSION: The results demonstrate that Ritalin LA administered once daily for
      up to 2 weeks achieved outcomes statistically superior to placebo in children
      with ADHD.

PMID- 14658925
TI  - Extracellular matrix induces formation of organoids and changes in cell surface
      morphology in cultured human breast carcinoma cells PMC42-LA.
AB  - In the lactating breast, the development of secretory alveoli consisting of
      differentiated cells arranged around a central lumen is dependent on signals from
      the extracellular environment of the cells. There are few cell lines that model
      this process. We previously showed that the human breast carcinoma line PMC42-LA
      can be induced to form organoids, reminiscent of secretory alveoli found in the
      lactating human breast. In this report, we used high-resolution scanning electron
      microscopy to show that the formation of organoids is accompanied by development
      of cell surface microvilli. Extracellular matrix-induced formation of microvilli
      occurred on the internal and external surfaces of cells in the organoids and not
      on surfaces in contact with the extracellular matrix. Organoid formation of PMC42
      LA cells induced a rearrangement of the extracellular matrix, seen in the form of
      radiating fibers from the organoids. In summary, there is an interaction between
      PMC42-LA cells and the underlying extracellular matrix, which leads to the
      formation of polarized cells with well-developed microvilli. This is accompanied
      by organization of the extracellular matrix. PMC42-LA is a relevant model of the
      human breast for investigations into cell-cell and cell-matrix interactions.

PMID- 14658927
TI  - Hypotension and bradycardia after elective carotid stenting: frequency and risk
      factors.
AB  - PURPOSE: To investigate the frequency of and risk factors for hypotension and
      bradycardia in response to elective carotid stenting and their association with
      neurological complications. METHODS: A retrospective analysis was conducted of
      471 patients (321 men; median age 72 years, interquartile range 64-77) who
      underwent elective carotid artery stenting without cerebral protection for high
      grade (>70%) symptomatic (n=147) or asymptomatic (n=324) internal carotid artery
      stenosis at a single center. Frequency and potential risk factors for severe
      hypotension (systolic blood pressure <80 mmHg) or bradycardia (heart rate <50
      bpm) were studied. RESULTS: Thirty-four (7%) patients had severe hypotension
      (n=23), bradycardia (n=2), or both (n=9) despite routine premedication with
      atropine and adequate fluid balance. Intravenous catecholamines (dopamine) were
      necessary in 8 patients with prolonged hypotension; none of the patients with
      bradycardia needed pacemaker support. Neurological complications (transient
      ischemic attack, minor stroke, major stroke, death) occurring in 33 (7%) patients
      were not significantly associated with hemodynamic instability (4/34 [12%] versus
      29/437 [7%], p=0.26). Age >77 years (fourth quartile; OR 6.40, 95% CI 1.80 to
      22.78, p=0.004) and coronary artery disease (OR 2.81, 95% CI 1.29 to 6.14,
      p=0.010) were associated with an increased adjusted risk for hypotension or
      bradycardia. CONCLUSIONS: Hemodynamic instability due to hypotension and
      bradycardia in response to carotid artery stenting occurs in a relatively low
      proportion of patients. Elderly patients and those with coronary artery disease
      are at highest risk. Although the rate of neurological complications was not
      significantly increased in patients with hemodynamic instability, the higher
      frequencies of neurological complications in these patients admonish us to be
      careful.

PMID- 14658928
TI  - Introduction: optimizing wakefulness in patients with fatigue and executive
      dysfunction.

PMID- 14658929
TI  - Primary care commentary: fatigue and executive dysfunction in the primary care
      setting.

PMID- 14658930
TI  - Brain circuits determine destiny in depression: a novel approach to the
      psychopharmacology of wakefulness, fatigue, and executive dysfunction in major
      depressive disorder.
AB  - Recent advances in neuropharmacology and neuroimaging are mapping the topography
      of symptoms in major depressive disorder (MDD). Different malfunctioning neuronal
      circuits apparently mediate different symptoms in MDD. Since all patients with
      MDD do not have the same symptoms, this implies that they may not all have the
      same malfunctioning circuits. Furthermore, since MDD patients treated with
      antidepressants commonly experience residual symptoms that prevent them from
      attaining complete remission, this implies that not all circuits are successfully
      targeted by treatment in such patients. A new neurobiologically informed
      treatment strategy for such patients calls for targeting residual symptoms by
      augmenting antidepressants with agents capable of boosting specific
      neurotransmitters in the hypothetically malfunctioning circuits. With this
      approach, the frequently residual symptoms of sleepiness, fatigue, and executive
      dysfunction can be targeted with bupropion, atomoxetine, modafinil, atypical
      antipsychotics, and stimulants.

PMID- 14658931
TI  - Role of executive function in late-life depression.
AB  - Late-onset depression has been conceptualized as a neurologic disease. This view
      has been supported by studies suggesting that late-onset depression is associated
      with cognitive impairment and neurologic comorbidity that may or may not be
      clinically evident when depression is first diagnosed. Findings implicating a
      dysfunction of frontostriatal-limbic pathways in geriatric depression have led to
      the depression-executive dysfunction (DED) syndrome hypothesis. Subsequent
      studies suggested that DED has slow, poor, or abnormal response to classical
      antidepressants. DED is characterized by psychomotor retardation, reduced
      interest in activities, impaired insight and pronounced behavioral disability.
      This clinical presentation begs the question whether agents that can selectively
      activate internal vigilance and therefore improve alertness have beneficial
      effects on DED. There is early evidence that psychosocial interventions aimed at
      improving the behavioral deficits of DED patients may also be effective in
      increasing remission rates and reducing depressive symptoms and disability.

PMID- 14658932
TI  - Treatment strategies for sleep disturbance in patients with depression.
AB  - Insomnia, excessive sleepiness, and fatigue are common symptoms in depressed
      patients. Excessive sleepiness is associated with impairments in cognitive and
      motor tasks and has a negative impact on social and occupational functioning.
      Further, sleepiness and fatigue strongly predict accidents. Conversely, problems
      with sleeplessness (e.g., difficulty falling asleep, frequent awakenings during
      the night, and early morning wakefulness) are also common symptoms in patients
      with depression. Recognition and treatment of sleep disturbance are important
      aspects of managing depression. Pharmacologic intervention and behavior
      modification are viable treatment strategies.

PMID- 14658933
TI  - Symptoms of fatigue and cognitive/executive dysfunction in major depressive
      disorder before and after antidepressant treatment.
AB  - Patients with major depressive disorder commonly experience fatigue and
      cognitive/executive dysfunction. These problems may be symptoms of the depression
      and persist despite effective antidepressant treatment, or these problems may
      emerge as adverse effects of some antidepressant treatments. A number of
      augmentation strategies can be employed to manage fatigue or cognitive/executive
      dysfunction, but the efficacy of these augmentation strategies must be researched
      further.

PMID- 14658934
TI  - Role of executive function in ADHD.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder
      characterized by inattention, hyperactivity, and impulsivity. ADHD is commonly
      treated with behavioral therapy and noradrenergic and dopaminergic
      pharmacotherapy with psychostimulants such as methylphenidate and
      dextroamphetamine. Stimulants primarily have dopaminergic and noradrenergic
      mechanisms of action, with blockade at the dopamine transporter reducing
      reuptake, resulting in an increase in these neurotransmitters at the synapse.
      Theoretically, inattention, hyperactivity, and impulsivity in ADHD may be due to
      underlying executive functioning, alerting, and orienting deficits, and the
      nonstimulant modafinil could be beneficial in managing symptoms of ADHD by
      improving these components of attention that accompany wakefulness. Although
      modafinil exhibits a small degree of dopaminergic action by blocking the dopamine
      transporter, the major effect of modafinil may be attributable to neuronal
      activity in the hypothalamus, particularly pertaining to the recently discovered
      peptides hypocretin 1 and 2 (also known as orexin A and B). However, further
      placebo-controlled and flexible-dose studies are needed to determine the efficacy
      of modafinil in treating the symptoms of ADHD in children and adults.

PMID- 14658935
TI  - The differential diagnosis of fatigue and executive dysfunction in primary care.
AB  - The diagnosis of the patient reporting fatigue or the signs of executive
      dysfunction can be perplexing for the primary care physician. Both symptoms are
      associated with a wide range of both somatic and psychiatric symptoms and often
      occur together, although they can exist independently. Using some simple
      diagnostic and mnemonic tools, such as BATHE, SIG E CAPS, and SWIKIR, may aid the
      clinician in differentiating possible causes of fatigue and executive dysfunction
      and determining whether they are signs of physical or mental disease.

PMID- 14658940
TI  - Symptoms and circuits, part 1: major depressive disorder.
AB  - ISSUE: Major depressive disorder comprises multiple symptoms. Each symptom may be
      mediated by separate and distinct neuronal circuits.

PMID- 14658941
TI  - The relationship between postpartum psychosis and bipolar disorder: a review.
AB  - BACKGROUND: The evidence for a spectrum of bipolar disorders is mounting. Of
      particular interest and importance is the evolution and recurrence of bipolar
      disorder in the postpartum period and its relationship to postpartum psychosis.
      Understanding whether such a phenomenological link exists has diagnostic,
      prognostic, and treatment implications. OBJECTIVES: A comprehensive review of (1)
      the literature regarding the relationships between postpartum psychosis and
      bipolar affective disorder, (2) the data regarding prophylactic treatment and
      acute management of postpartum psychosis and bipolar disorder in the puerperium,
      and (3) critical areas for future research. STUDY DESIGN: MEDLINE and PubMed
      (1966-2002) databases were searched for English-language articles using the
      keywords postpartum/puerperal depression, puerperal/postpartum psychosis, bipolar
      disorder, lithium, anticonvulsants, antipsychotics, and breastfeeding. RESULTS:
      Evidence from studies of women with a history of bipolar disorder, longitudinal
      studies of women with puerperal episodes of psychosis, and family studies support
      a link between postpartum psychosis and bipolar disorder. CONCLUSIONS:
      Understanding the relationship between postpartum psychosis and bipolar disorder
      has implications for perinatal and long-term treatment. Prophylactic treatment of
      women with bipolar disorder and/or a history of postpartum psychosis may be
      indicated. Epidemiological, genetic, and pharmacologic research must be completed
      to understand, prevent, and adequately treat postpartum psychosis.

PMID- 14658942
TI  - Cost and outcome implications of using typical and atypical antipsychotics in
      ordinary practice in Italy.
AB  - BACKGROUND: It is uncertain whether atypical antipsychotic agents, as prescribed
      in ordinary practice, are a cost-effective alternative to conventional agents.
      This study examined the financial and clinical implications of using atypical
      antipsychotics in the context of community psychiatric care in Italy. METHOD:
      Service costs and outcome data over a 24-month period (June-November 1999 to June
      November 2001) were compared between 2 cohorts of ICD-10-diagnosed subjects, the
      first including patients receiving atypical and the second typical
      antipsychotics, according to the type of treatment received at the beginning of
      the study. RESULTS: At baseline, 183 subjects were under treatment with
      antipsychotic drugs, of whom 73 were treated with atypical agents. Most patients
      had a diagnosis of schizophrenia and only a minority were first-contact patients.
      Conventional antipsychotics were used in more chronic and elderly patients, while
      atypicals were prescribed in more severe and recently diagnosed cases. After
      background group differences were controlled for, the use of atypical agents was
      neither predictive of higher total health care costs nor of better patient
      outcome. Predictors of higher costs and better outcome were severity of illness
      at baseline and first-contact patients. CONCLUSIONS: The introduction of atypical
      agents had a small impact in terms of total health care costs and outcome, and
      more important than the agent prescribed was the severity of illness.

PMID- 14658943
TI  - Comparison of clinical characteristics and comorbidity in schizophrenia patients
      with and without obsessive-compulsive disorder: schizophrenic and OC symptoms in
      schizophrenia.
AB  - BACKGROUND: Since a substantial proportion of schizophrenia patients has symptoms
      of obsessive-compulsive disorder (OCD), we sought to provide a phenomenological
      characterization of a schizophrenia subgroup with OCD. METHOD: A consecutive
      sample of patients who met DSM-IV criteria for both schizophrenia and OCD (N =
      55) was compared with 55 schizophrenia patients without OCD matched for age and
      number of hospitalizations. Structured Clinical Interview for DSM-IV Axis I
      psychiatric disorders (SCID-I), including a specific module for tic disorders
      based on DSM-IV criteria, Scales for the Assessment of Positive and Negative
      Symptoms, Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impressions
      scale, and Hamilton Rating Scale for Depression were used. RESULTS: Schizophrenia
      patients with OCD (N = 55) had lower positive dimension scores than schizophrenia
      patients without OCD (N = 55) (p =.01). Two subgroups of schizo-obsessive
      patients were identified: OCD independent of schizophrenia symptoms and OCD
      partially overlapping positive schizophrenia symptoms. Schizophrenia patients
      with OCD had more SCID-detectable OCD-spectrum disorder, primarily body
      dysmorphic disorder and chronic tic disorders. More schizophrenia patients with
      OCD were treated with either add-on serotonin reuptake inhibitors or clozapine.
      CONCLUSION: Schizophrenia patients with OCD differ from their non-OCD
      schizophrenia counterparts in severity of schizophrenia symptoms, co-occurrence
      of OCD-spectrum disorders, and pharmacotherapy. These findings and the
      identification of 2 subgroups of schizo-obsessive patients support the validity
      of this unique clinical entity and may facilitate the establishment of diagnostic
      criteria for a schizo-obsessive subtype of schizophrenia.

PMID- 14658944
TI  - Partial compliance and patient consequences in schizophrenia: our patients can do
      better.
AB  - OBJECTIVE: The primary objective of this review is to evaluate the strategies
      used to improve patient compliance with antipsychotic medication in the treatment
      of schizophrenia. DATA SOURCES: An electronic literature search of relevant
      studies using MEDLINE and the Cochrane Library (January 1974-December 2002) was
      performed using the search terms adherence, antipsychotic, atypical, compliance,
      conventional, and schizophrenia. STUDY SELECTION: English-language and non
      English-language articles, references from bibliographies of reviews, original
      research articles, and other articles of interest were reviewed. DATA EXTRACTION:
      Data quality was determined by publication in the peer-reviewed literature and
      the most important information was identified. DATA SYNTHESIS: Atypical
      antipsychotics are associated with an improved side-effect profile and reduced
      risk of relapse compared with the older agents. Additional benefit may be
      provided by long-acting injectable formulations as they provide the confidence of
      continuous medication coverage. CONCLUSIONS: Successful treatment of patients
      with schizophrenia requires acknowledgment that partial compliance will present a
      major barrier to achieving maximum outcomes. Ideally, all patients suspected of
      partial compliance should be considered suitable for treatment with a long-acting
      injectable atypical antipsychotic.

PMID- 14658945
TI  - A prospective, open-label, flexible-dose study of quetiapine in the treatment of
      delirium.
AB  - BACKGROUND: Delirium is an organic psychiatric syndrome characterized by
      fluctuating consciousness and impaired cognitive functioning. High-potency
      typical neuroleptics have traditionally been used as first-line drugs in the
      treatment of delirium. However, these drugs are frequently associated with
      undesirable adverse events including extrapyramidal symptoms (EPS). The purpose
      of the present open-label, flexible-dose study was to provide preliminary data on
      the usefulness and safety of quetiapine for patients with delirium. METHOD:
      Twelve patients with DSM-IV delirium were treated with flexible doses of open
      label quetiapine (mean +/- SD dosage = 44.9 +/- 31.0 mg/day). To evaluate the
      usefulness and safety of quetiapine, scores from the Delirium Rating Scale,
      Japanese version, were assessed every day (for 1 outpatient, at least twice per
      week), and scores from the Mini-Mental State Examination, Japanese version, and
      the Drug-Induced Extrapyramidal Symptom Scale were assessed at baseline and after
      remission of delirium. Data were gathered from April to October 2001. RESULTS:
      All patients achieved remission of delirium several days after starting
      quetiapine (mean +/- SD duration until remission = 4.8 +/- 3.5 days). Quetiapine
      treatment was well tolerated, and no clinically relevant change in EPS was
      detected. CONCLUSION: Quetiapine may be a useful alternative to conventional
      neuroleptics in the treatment of delirium due to its rapid onset and relative
      lack of adverse events. Further double-blind, placebo-controlled studies are
      warranted.

PMID- 14658946
TI  - Escitalopram in the treatment of panic disorder: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Escitalopram, the therapeutically active isomer of the racemic
      selective serotonin reuptake inhibitor antidepressant citalopram, has shown
      significant anxiolytic effects in placebo-controlled clinical trials of social
      anxiety disorder, generalized anxiety disorder, and anxiety symptoms associated
      with major depression. This study evaluated the safety and efficacy of
      escitalopram in outpatients diagnosed with panic disorder. METHOD: Male and
      female outpatients between 18 and 80 years of age meeting DSM-IV criteria for
      panic disorder, with or without agoraphobia, were randomly assigned to 10 weeks
      of double-blind treatment with escitalopram, citalopram, or placebo in a study
      conducted from September 1999 to July 2001. The primary measure of efficacy was
      panic attack frequency at week 10 relative to baseline, as assessed by the
      Modified Sheehan Panic and Anticipatory Anxiety Scale. RESULTS: A total of 366
      subjects (128 escitalopram patients, 119 citalopram patients, and 119 placebo
      patients) received at least 1 dose of double-blind treatment. The frequency of
      panic attacks was statistically significantly improved (p =.04), and the increase
      in percentage of patients with zero panic attacks reached borderline significance
      (p =.051), in the escitalopram-treated group relative to the placebo-treated
      group. Both escitalopram and citalopram statistically significantly reduced panic
      disorder symptoms and severity versus placebo at endpoint (p </=.05), as measured
      by the Panic and Agoraphobia Scale total score, the Clinical Global Impressions
      scale, the Patient Global Evaluation, and the Quality of Life Enjoyment and
      Satisfaction Questionnaire. Treatment with escitalopram was safe and well
      tolerated, with a similar incidence of the most common adverse events for the
      escitalopram and placebo groups. The rate of discontinuation for adverse events
      was 6.3% for escitalopram, 8.4% for citalopram, and 7.6% for placebo. CONCLUSION:
      Escitalopram is efficacious, safe, and well tolerated in the treatment of panic
      disorder.

PMID- 14658947
TI  - Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib
      and other nonsteroidal anti-inflammatory drugs.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to
      increase serum lithium concentrations. We sought to determine whether NSAIDs that
      selectively inhibit cyclooxygenase (COX) 2 also elevate serum lithium
      concentrations. METHOD: The U.S. Food and Drug Administration's Adverse Event
      Reporting System (AERS) database was searched in January 2003 for reports of
      interactions between lithium and rofecoxib or celecoxib, the selective COX-2
      inhibitors marketed in the United States. Additionally, a literature search was
      performed using PubMed with the MeSH terms anti-inflammatory agents, nonsteroidal
      and lithium. Reports of interactions between NSAIDs and lithium were selected for
      review based on titles of retrieved citations. RESULTS: Eighteen cases of
      increased serum lithium concentrations after the addition of one of the COX-2
      inhibitors to stable lithium therapy were retrieved from AERS, 13 with rofecoxib
      and 5 with celecoxib. Serum lithium concentration increases of up to 99% and 448%
      with concomitant celecoxib and rofecoxib use, respectively, were reported. Thirty
      six English-language literature articles report interactions between lithium and
      various NSAIDs. Although some articles report no effect or decreased serum
      lithium concentrations with concomitant aspirin or sulindac, increased serum
      lithium concentration reports exist for aspirin, sulindac, and 14 other NSAIDs,
      including celecoxib and rofecoxib. CONCLUSION: Clinicians should consider NSAID
      use in the differential diagnosis of lithium toxicity, monitor patients' serum
      lithium concentrations during the initiation or discontinuation of NSAID therapy,
      and be aware that the selective COX-2 inhibitors can increase serum lithium
      concentrations leading to toxicity.

PMID- 14658948
TI  - Treatment of bulimia nervosa with topiramate in a randomized, double-blind,
      placebo-controlled trial, part 1: improvement in binge and purge measures.
AB  - BACKGROUND: This randomized, double-blind, placebo-controlled trial was designed
      to assess the efficacy and safety of topiramate in bulimia nervosa. METHOD:
      Patients with DSM-IV bulimia nervosa were randomly assigned in equal proportions
      to receive topiramate (N = 35) or placebo (N = 34) for 10 weeks (between April
      1999 and Dec. 2000). Topiramate treatment was started at 25 mg/day and titrated
      by 25 to 50 mg/week to a maximum of 400 mg/day. The primary efficacy measure was
      mean weekly number of binge and/or purge days. Related outcome measures included
      mean weekly number of binge days and binge frequency, as well as mean weekly
      number of purge days and purge frequency. RESULTS: Sixty-four outpatients (33
      placebo, 31 topiramate) were included in the intent-to-treat analysis. The median
      topiramate dose was 100 mg/day (range, 25-400 mg/day). Mean +/- SD baseline
      number of weekly binge and/or purge days was 5.0 +/- 1.6 for topiramate patients
      and 5.1 +/- 1.5 for placebo patients. The primary efficacy measure, mean weekly
      number of binge and/or purge days, decreased 44.8% from baseline with topiramate
      versus 10.7% with placebo (p =.004). The mean weekly number of binge days
      decreased 48.2% with topiramate versus 17.7% with placebo (p =.015), and mean
      binge frequency decreased 49.2% with topiramate versus 28.0% with placebo (p
      =.071). The mean weekly number of purge days decreased 43.4% with topiramate
      versus 16.6% with placebo (p =.016), and mean purge frequency decreased 49.8%
      with topiramate versus 21.6% with placebo (p =.016). Three patients (2 placebo, 1
      topiramate) discontinued from the trial due to adverse events. CONCLUSION:
      Topiramate was associated with significant improvements in both binge and purge
      symptoms in this study population and represents a potential treatment for
      bulimia nervosa.

PMID- 14658949
TI  - Risperidone for severe tardive dyskinesia: a 12-week randomized, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: Risperidone has been reported to alleviate the severity of tardive
      dyskinesia, but without placebo control, the possibility of spontaneous tardive
      dyskinesia remission after discontinuing original conventional antipsychotics
      cannot be excluded. This 12-week randomized, double-blind, placebo-controlled
      study investigated the effect of risperidone on severe tardive dyskinesia.
      METHOD: Forty-nine DSM-IV schizophrenia patients with severe tardive dyskinesia
      were enrolled in the study. After a 4-week washout period, the subjects were
      randomly assigned to treatment with either risperidone or placebo. The
      risperidone dose was started at 2 mg/day and gradually increased to 6 mg/day over
      6 weeks; the 6-mg/day dose was maintained for the remaining 6 weeks of the study.
      The subjects were evaluated every 2 weeks with the Abnormal Involuntary Movement
      Scale (AIMS) and the Extrapyramidal Symptom Rating Scale. The final mental status
      was assessed with the Brief Psychiatric Rating Scale. RESULTS: Twenty-two
      subjects in the risperidone group and 20 subjects in the placebo group completed
      the study; the mean baseline AIMS total score for all subjects was 15.9 +/- 4.6.
      At the end of the study, the mean AIMS total score decrease was 1.1 +/- 4.8 in
      the placebo group and 5.5 +/- 3.8 in the risperidone group (p <.05). Fifteen
      subjects (68%) in the risperidone group and 6 subjects (30%) in the placebo group
      were responders (p <.05). The risperidone responders had a mean AIMS total score
      decrease of 7.5 +/- 2.1. More significant tardive dyskinesia improvement among
      the risperidone group was noted from the eighth week and was mainly demonstrated
      in the buccolinguomasticatory a rea rather than in choreoathetoid movement of the
      extremities (p <.001). CONCLUSIONS: Risperidone, 6 mg/day, can improve tardive
      dyskinesia more significantly than discontinuing antipsychotics in patients with
      severe tardive dyskinesia, especially in the orofacial areas.

PMID- 14658950
TI  - Long-term antidepressant efficacy and safety of olanzapine/fluoxetine
      combination: a 76-week open-label study.
AB  - BACKGROUND: The olanzapine/fluoxetine combination has demonstrated effectiveness
      in treatment-resistant depression (TRD). Although this combination is being used
      by prescribers, this is the first study to examine long-term use. Long-term
      efficacy and safety were therefore investigated in a group of patients with major
      depressive disorder (MDD) with and without TRD. METHOD: 560 patients who met DSM
      IV diagnostic criteria for MDD were enrolled in this 76-week, open-label study
      (Feb. 2000-July 2002). The Montgomery-Asberg Depression Rating Scale (MADRS)
      total score was the primary efficacy measure. Safety was assessed via adverse
      events, vital signs, laboratory analytes, electrocardiography, and extrapyramidal
      symptom measures. RESULTS: MADRS mean total scores decreased 7 points from
      baseline (31.6 [N = 552]) at 1/2 week of treatment, 11 points at 1 week of
      treatment, and 18 points at 8 weeks of treatment. This effect was maintained to
      endpoint with a mean decrease of 22 points at 76 weeks. Response and remission
      rates for the total sample were high (62% and 56%, respectively), and the relapse
      rate was low (15%). Response, remission, and relapse rates for TRD patients (N =
      145) were 53%, 44%, and 25%, respectively. The most frequently reported adverse
      events were somnolence, weight gain, dry mouth, increased appetite, and headache.
      At endpoint, there were no clinically meaningful changes in vital signs,
      laboratory analytes, or electrocardiography. There were no significant increases
      on any measure of extrapyramidal symptoms. CONCLUSIONS: The olanzapine/fluoxetine
      combination showed rapid, robust, and sustained improvement in depressive
      symptoms in patients with MDD, including patients with TRD. The long-term safety
      profile of the combination was similar to that of its component monotherapies.

PMID- 14658951
TI  - Psychiatric comorbidity as a predictor of clinical response to nortriptyline in
      treatment-resistant major depressive disorder.
AB  - BACKGROUND: A number of studies of major depressive disorder suggest that
      psychiatric co-morbidity may contribute to treatment resistance. The purpose of
      this study was to test whether the presence of comorbid Axis I and Axis II
      disorders predicts clinical response to an open trial of nor-triptyline among
      patients with treatment-resistant depression. METHOD: Ninety-two outpatients with
      treatment-resistant DSM-III-R major depressive disorder were enrolled in a 6-week
      open trial of nor-triptyline (Nov. 1992-Jan. 1999). The presence of comorbid Axis
      I and Axis II disorders was established at baseline with the use of the
      Structured Clinical Interview for DSM-III-R. Chi-square analyses were used to
      test Axis I or Axis II co-morbid conditions as a predictor of clinical response
      to nortriptyline. RESULTS: Thirty-nine patients (42.4%) responded to
      nortriptyline. The presence of avoidant personality disorder (p <.01) predicted
      poorer response to nortriptyline. The response rate was 16.7% for patients with
      and 48.6% for patients without comorbid avoidant personality disorder. No other
      comorbid diagnoses were found to predict clinical response in a statistically
      significant manner. CONCLUSION: The presence of avoidant personality disorder
      conferred a poorer prognosis in treatment-resistant depression patients treated
      with nortriptyline.

PMID- 14658952
TI  - Prolactin levels during long-term risperidone treatment in children and
      adolescents.
AB  - BACKGROUND: This analysis was designed to investigate prolactin levels in
      children and adolescents on long-term risperidone treatment and explore any
      relationship with side effects hypothetically attributable to prolactin (SHAP).
      METHOD: Data from 5 clinical trials (total N = 700) were pooled for this post hoc
      analysis. Children and adolescents aged 5 to 15 years with subaverage
      intelligence quotients and conduct or other disruptive behavior disorders
      received risperidone treatment (0.02-0.06 mg/kg/day) for up to 55 weeks. Outcome
      measures analyzed included serum prolactin levels, reported adverse events, and
      the conduct problem subscore of the Nisonger Child Behavior Rating Form. RESULTS:
      Mean prolactin levels rose from 7.8 ng/mL at baseline to a peak of 29.4 ng/mL at
      weeks 4 to 7 of active treatment, then progressively decreased to 16.1 ng/mL at
      weeks 40 to 48 (N = 358) and 13.0 ng/mL at weeks 52 to 55 (N = 42). There was no
      relationship between pro-lactin levels and age. Females returned to a mean value
      within the normal range (</= 30 ng/mL) by weeks 8 to 12, and males were close to
      normal values (</= 18 ng/mL) by weeks 16 to 24. At least 1 SHAP was reported by
      13 (2.2%) of 592 children. There was no direct correlation between prolactin
      elevation and SHAP. CONCLUSION: With long-term risperidone treatment in children
      and adolescents, serum prolactin levels tended to rise and peak within the first
      1 to 2 months and then steadily decline to values within or very close to the
      normal range by 3 to 5 months.

PMID- 14658953
TI  - The attribution of somatization in schizophrenia patients: a naturalistic follow
      up study.
AB  - BACKGROUND: Knowledge is limited concerning somatic symptoms that cannot be
      accounted for by detectable somatic illness among schizophrenia patients. This
      study aimed to explore the prevalence, correlates, and predictors of somatization
      among schizophrenia patients. METHOD: Initial data on all consecutively admitted
      adult patients with DSM-IV schizophrenia, schizoaffective disorder, major
      depressive disorder, or bipolar disorder were collected between August 1998 and
      August 2000. Standardized measures of psychopathology, somatization, emotional
      distress, adverse effects, insight, and stress process-related (psychosocial)
      variables were administered to 237 schizophrenia patients at admission and at
      least 12 months thereafter (N = 148). Partial correlation and multiple regression
      analyses were performed. RESULTS: The frequency of somatization, defined as the
      presentation of 5 or more medically unexplained somatic symptoms (Somatic Symptom
      Index-5), among the inpatient population (27%) did not change significantly after
      at least 12 months (30%; p =.61). Regression analysis showed that somatization
      scores were best predicted by the combination of scores for emotional distress
      attributed to psychopathology and side effects, expressed emotion, and insight.
      This combined model explains at least 40% of the variance in somatization scores.
      Self-esteem and social support showed negative association with somatization
      scores. Somatization scores were not associated with gender, age, education, age
      at onset, observed severity of psychopathology, subtype and duration of illness,
      number of admissions and treatment settings, or type and dose of antipsychotic
      agents. CONCLUSIONS: Somatization is a prevalent problem among schizophrenia
      patients and is associated with emotional distress attributed to psychopathology,
      side effects of antipsychotic agents, and family members' attitudes toward
      schizophrenia patients. This study suggests that insight, self-esteem, and social
      support may protect against somatization in schizophrenia patients.

PMID- 14658954
TI  - New developments in antipsychotic therapy.

PMID- 14658955
TI  - Amitriptyline: dual-action antidepressant?

PMID- 14658957
TI  - Can donepezil be considered a mild antipsychotic in dementia treatment? A report
      of donepezil use in 6 patients.

PMID- 14658958
TI  - Mania from dose-related ziprasidone augmentation of an SSRI.

PMID- 14658959
TI  - Successful treatment with clozapine at higher doses after clozapine-induced
      priapism.

PMID- 14658960
TI  - Deconstructing psychiatric disorders, part 2: An emerging, neurobiologically
      based therapeutic strategy for the modern psychopharmacologist.

PMID- 14658961
TI  - The dilemma of unmodified electroconvulsive therapy.

PMID- 14658962
TI  - Are antidepressants carcinogenic? A review of preclinical and clinical studies.
AB  - BACKGROUND: Antidepressants are widely prescribed for mood and anxiety disorders,
      though reports in the oncology and epidemiology literature have suggested these
      agents may possess tumor initiating and/or promoting properties, raising
      questions about safe long-term use in patients. The author conducted a review of
      the preclinical and clinical literature on the connection between antidepressants
      and carcinogenesis. METHOD: A MEDLINE search was conducted for English-language
      articles published from 1966 to 2002 using the search terms antidepressants,
      tumors, carcinogenesis, and cancer, as well as specific antidepressant names.
      Additional studies were ascertained through cross-references. RESULTS:
      Preclinical studies found evidence for both tumor promotion and suppression,
      though the majority of studies predominantly examined tricyclic antidepressants
      (TCAs), with 1 report suggesting that TCAs with a nitrogen atom in the central
      ring are genotoxic. Of 13 clinical studies, 3 found a significant increase, 4
      noted a trend increase, and 6 found no increase in risk for cancer with
      antidepressant (mostly TCA) use. Methodologic differences could account for some
      of the discrepancies found in the clinical studies, while questions about the
      validity for humans of the preclinical models raise doubt about the significance
      of those findings. CONCLUSION: While there is some suggestive evidence of an
      association between antidepressant use and cancer, the link is, at this time,
      questionable but deserving of further study, especially with newer agents.
      Clinicians should not withhold antidepressant medication when indicated, as the
      risks of untreated depressive and anxiety disorders exceed the as yet
      unsubstantiated risk of tumor formation in such patients.

PMID- 14658963
TI  - Methylphenidate treatment for attention-deficit/hyperactivity disorder in
      children and adolescents with velocardiofacial syndrome: an open-label study.
AB  - BACKGROUND: Velocardiofacial syndrome (VCFS) is a common microdeletion syndrome
      associated with psychiatric morbidity and developmental disabilities. Although
      attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric
      problem associated with VCFS, there are no reports on methylphenidate treatment
      in this patient population. Indeed, clinicians have commonly avoided the use of
      methylphenidate in children with VCFS because of concerns about ineffectiveness
      or psychotic exacerbation. METHOD: Forty subjects of mean +/- SD age 11.0 +/- 5.0
      years with VCFS were assessed for DSM-IV diagnoses using the Schedule for
      Affective Disorders and Schizophrenia for School-Aged Children, Present and
      Lifetime Version, and its extended ADHD module (K-SADS-P-ADHD). Those found to
      have comorbid ADHD were treated with methylphenidate, 0.3 mg/kg once daily.
      Treatment efficacy was evaluated after 4 weeks with the K-SADS-P-ADHD, the
      Conners' Abbreviated Teacher Questionnaire, and the Conners' Continuous
      Performance Test. Side effects were evaluated with a modified version of the
      Barkley Side Effects Rating Scale. RESULTS: Of the 18 subjects (45%) diagnosed
      with ADHD, 12 agreed to participate in the study. Their ADHD symptoms, both
      behavioral and cognitive, improved significantly with treatment. None of the
      patients showed clinical worsening or psychotic symptoms. Side effects were
      usually mild and did not warrant discontinuation of methylphenidate. The most
      common side effects were anorexia and depressive-like symptoms. CONCLUSION: This
      open-label study indicates that methylphenidate is effective and safe in patients
      with VCFS. Therefore, its current limited use in this population seems to be
      unjustified. Larger, controlled clinical and pharmacogenetic studies are needed
      to confirm these findings.

PMID- 14658964
TI  - Occult mood disorders in 104 consecutively presenting children referred for the
      treatment of attention-deficit/hyperactivity disorder in a community mental
      health clinic.
AB  - OBJECTIVE: To ascertain the prevalence of mood disorders among consecutively
      evaluated prepubertal children presenting for the treatment of attention
      deficit/hyperactivity disorder (ADHD) in a community mental health clinic.
      METHOD: 104 children received systematic assessments designed to identify
      individuals meeting the DSM-IV criteria for major depressive disorder (MDD),
      mania, and ADHD. "Standard" and "modified" criteria for mania were employed.
      Modified criteria, in an effort to minimize false-positive diagnoses of mania,
      required the presence of euphoria and/or flight of ideas. A child meeting the
      criteria for MDD or either set of criteria for mania was categorized as having a
      mood disorder. Mood disorders in first-degree relatives were assessed using a
      systematic interview. Data were gathered from 2000 to 2002. RESULTS: Sixty-two
      children (59.6%) had a mood disorder. Compared with those who did not have a mood
      disorder, they were 3.3 times more likely (54.8% vs. 16.7%) to have a family
      history of any affective disorder (p <.0001) and 18.3 times more likely (43.5%
      vs. 2.4%) to have a family history of bipolar disorder (p <.0001). Twenty (32.3%)
      of the children with and none without a mood disorder had psychotic features (p
      <.0001). Compared with those meeting only the standard criteria for mania, those
      meeting the modified criteria were 9.1 times more likely (69.8% vs. 7.7%) to have
      a family history of an affective disorder (p <.0001) and 7.3 times more likely
      (55.8% vs. 7.7%) to have a family history of bipolar disorder (p =.002).
      CONCLUSION: Children who presumably have ADHD often have unrecognized affective
      illness. Our findings support the view that children meeting the modified
      criteria for mania have veritable bipolar disorder. These findings, which were
      derived in the course of delivering routine clinical services in a community
      mental health clinic, are consistent with those obtained in research settings
      suggesting that children presenting with ADHD often have occult mood disorders,
      especially unrecognized bipolarity. We suggest that clinicians encountering
      children with prominent features of ADHD inquire about the presence of euphoria
      and flight of ideas. We submit that the presence of these "classic"
      manifestations of mania strongly suggests the presence of occult bipolarity, even
      if course of illness otherwise markedly deviates from "classic" descriptions.

PMID- 14658965
TI  - Sexual satisfaction and risk of disability in older women.
AB  - BACKGROUND: Most studies evaluating sexuality in older adults have focused on
      men, and relatively little research has evaluated the relationship between sexual
      satisfaction and health outcomes in older women. The aims of this study were to
      describe correlates of sexual satisfaction in community-dwelling older women with
      moderate to severe levels of disability and to examine the association of sexual
      satisfaction with progression of disability in this population. METHOD: A total
      of 980 moderately to severely disabled women aged 65 years or older who had
      participated in The Women's Health and Aging Study entered this study. Baseline
      evaluations took place from 1992 through 1995. Participants rated their
      satisfaction with their level of sexual activity on a 0-to-10 scale. Women
      scoring > or = 8 were considered sexually satisfied. The onset of new severe
      disability was determined by semiannual assessments, over 3 years, of disability
      in performing activities of daily living (ADLs) and walking across a room.
      RESULTS: Of 203 (49.8%) women living with a spouse, 101 were satisfied with their
      level of sexual activity. In this group, older age, white race, and higher level
      of physical function were independent predictors of sexual satisfaction. In
      addition, among women living with a spouse, higher sexual satisfaction was
      associated with a significantly decreased risk for incident disability in
      performing ADLs (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.36 to
      0.94) and walking across a small room (HR = 0.38, 95% CI = 0.18 to 0.79). Among
      women not living with a spouse, the response on the sexual satisfaction question
      showed different determinants and was not associated with disability risk.
      CONCLUSION: Sexual satisfaction in community-dwelling, older, disabled women
      living with their spouse is associated with reduced risk for subsequent new
      severe disabilities.

PMID- 14658966
TI  - Divalproex sodium for the treatment of conduct disorder: a randomized controlled
      clinical trial.
AB  - BACKGROUND: New treatments for conduct disorder are sorely needed. We aimed to
      test the efficacy of divalproex sodium for the treatment of conduct disorder.
      METHOD: Seventy-one youths with conduct disorder according to DSM-IV criteria
      were enrolled in a randomized, controlled, 7-week clinical trial. Subjects were
      all adolescent males with at least 1 crime conviction. Subjects were randomized
      into high- and low-dose conditions and were openly managed by a clinical team.
      Subjects and independent outcome raters were blinded to condition. Clinical
      Global Impressions-Severity of Illness (CGI-S) and CGI-Improvement (CGI-I)
      ratings, Weinberger Adjustment Inventory ratings, and staff ratings of behavioral
      privilege were used to assess outcome. RESULTS: Intent-to-treat analyses showed
      significant associations between assignment to the high-dose condition and
      ratings on the CGI-S (p =.02) and CGI-I (p =.0008). Self-reported weekly impulse
      control was significantly better in the high-dose condition (p <.05), and
      association between improvement in self-restraint and treatment condition was of
      borderline statistical significance (p <.06). Parallel analyses comparing outcome
      by blood drug level achieved strengthened the results, as expected. CONCLUSION:
      This preliminary study in a most difficult population suggests a role for
      divalproex sodium in the treatment of conduct disorder. Divalproex sodium
      improved self-reported impulse control and self-restraint, variables shown to be
      predictive of criminal recidivism. Studies are needed of longer-term impact and
      side-effect profiles. This is one of few controlled psychopharmacologic studies
      of conduct disorder.

PMID- 14658967
TI  - High-dose olanzapine and prolactin levels.
AB  - BACKGROUND: This study evaluates whether high-dose olanzapine is associated with
      elevation of serum prolactin levels. METHOD: Twenty-four patients taking daily
      doses of olanzapine of 20, 25, 30, and 40 mg for DSM-IV schizophrenia or
      schizoaffective disorder had serum prolactin levels measured. The patients were
      all from one author's (J.L.K.'s) clinical practice. The mean duration of
      olanzapine therapy was 15.3 months at a dose of at least 20 mg/day. Data were
      gathered in 2000 and 2001. RESULTS: There was no significant correlation between
      olanzapine dose and prolactin level (Pearson product moment correlation
      coefficient = 0.09). No significant differences were found between mean prolactin
      values in each dose group. CONCLUSION: There was no significant elevation of
      prolactin with higher doses of olanzapine. Thus, preliminary evidence suggests
      that using higher doses of olanzapine is generally safe with regard to prolactin
      levels.

PMID- 14658968
TI  - The effects of breathing-related sleep disorders on mood disturbances in the
      general population.
AB  - BACKGROUND: Results of clinical studies suggest that there may be a relationship
      between breathing-related sleep disorders and depressive disorders. This study
      aims to assess the impact of breathing-related sleep disorder on major depressive
      disorder in the general population. METHOD: A cross-sectional telephone survey
      was carried out between 1994 and 1999 in the general population of the United
      Kingdom, Germany, Italy, Portugal, and Spain. A total of 18,980 randomly selected
      subjects aged 15 to 100 years and representative of the general population of
      their respective countries participated in the study. The questionnaire included
      a series of questions about sleep quality, breathing-related sleep disorder
      symptoms, mental disorders, and medical conditions. Data are presented using
      point prevalence. RESULTS: 2.1% of the subjects were found with obstructive sleep
      apnea syndrome at the time of the interview, and 2.5% had some other type of DSM
      IV breathing-related sleep disorder diagnosis. The association of DSM-IV
      breathing-related sleep disorder diagnosis and major depressive disorder
      diagnosis was found in 0.8% of the sample. As many as 18% of individuals with a
      major depressive disorder diagnosis also have a DSM-IV breathing-related sleep
      disorders diagnosis, and 17.6% of subjects with a DSM-IV breathing-related sleep
      disorders diagnosis have a major depressive disorder diagnosis. Multivariate
      models showed that even after controlling for obesity and hypertension, the odds
      of having a DSM-IV breathing-related sleep disorders diagnosis was 5.26 for
      individuals with a major depressive disorder diagnosis. CONCLUSION: About 800 of
      100,000 individuals have both a breathing-related sleep disorder and a major
      depressive disorder. The identification of 1 of these 2 disorders should prompt
      the investigation of the other disorder since nearly a fifth of them have the
      other disorder.

PMID- 14658969
TI  - Economic consequences of not recognizing bipolar disorder patients: a cross
      sectional descriptive analysis.
AB  - BACKGROUND: This retrospective study compared treatment patterns and costs for
      patients with recognized and unrecognized bipolar disorder with those of
      depressed patients without a bipolar disorder claim. METHOD: Claims data for 7
      large national employers covering 585,584 persons aged less than 65 years were
      used to identify patients diagnosed with depression and initially treated with
      antidepressants. Data on employees, as well as spouses and dependents, for the
      period 1998 to mid-2001 were used. Patients were identified as bipolar based on
      the criteria of a bipolar diagnosis claim (ICD-9 codes: 296.0, 296.1, 296.4
      296.8) and/or a mood stabilizer prescription claim. Of the patients identified as
      bipolar, unrecognized bipolar disorder (unrecognized-BP) patients met the
      criteria after antidepressant initiation, while recognized bipolar disorder
      (recognized-BP) patients met the criteria at or before initiation. The remaining
      patients in the sample were non-bipolar depressed (non-BP) patients. Outcome
      measures included treatment patterns and monthly medical costs in the 12 months
      subsequent to initiation of antidepressant treatment. RESULTS: Of the 9009
      patients treated for depression with antidepressants, there were 8383 non-BP
      patients (93.1%), 293 recognized-BP patients (3.3%), and 333 unrecognized-BP
      patients (3.7%). Use of combination therapies varied among the non-BP (11%),
      unrecognized-BP (32%), and recognized-BP patients (44%) (all pairwise p <.01).
      Use of mood stabilizers was less frequent among unrecognized-BP patients (14%)
      than recognized-BP patients (34%) (p <.0001). Unrecognized-BP patients incurred
      significantly greater (p <.05) mean monthly medical costs ($1179 US dollars) in
      the 12 months following initiation of antidepressant treatment compared with
      recognized-BP patients ($801 US dollars) and non-BP patients ($585 US dollars).
      Monthly indirect costs were significantly greater (p <.05) for unrecognized-BP
      ($570 US dollars) and recognized-BP ($514 US dollars) employees compared with non
      BP employees ($335 US dollars) in the 12 months following antidepressant
      initiation. CONCLUSIONS: Patterns of medication treatment for bipolar disorder
      were suboptimal. Accurate and timely recognition of bipolar disease was
      associated with lower medical costs and lower indirect costs due to work loss.

PMID- 14658970
TI  - The impact of attempted suicide on the symptoms and course of mood disorders.
AB  - BACKGROUND: Case-controlled studies have produced conflicting results on the
      relief of depression following attempted suicide. This study examined the impact
      of attempted suicide on the symptoms and course of mood disorders. METHOD: Of
      2800 inpatients reviewed retrospectively, 40 depressed patients who had attempted
      suicide immediately before admission and 40 depressed but nonsuicidal control
      patients satisfied entry criteria for the study. The overall severity of their
      depression had been rated by the treating psychiatrists before the attempted
      suicide or at admission using the DSM-III-R (or DSM-IV) severity scale. The
      severity of depression at 1 week after admission was evaluated by reviewing
      medical records. For categorical analysis, improvement was defined as a reduction
      of one or more categories on the DSM-III-R (or DSM-IV) severity scale. We
      assigned scores of 1-6 to this scale to enable quantitative comparisons. RESULTS:
      Both categorical and dimensional analyses demonstrated that depression was
      significantly (p <.05) more likely to improve within 1 week of admission among
      suicidal unipolar patients than among nonsuicidal unipolar patients. Logistic
      regression analyses revealed that a unipolar course was significantly (p =.023)
      associated with the improvement of depression. Of the 15 patients showing
      postsuicidal improvement of depression, 5 (33%) relapsed within 1 month. No
      significant predictors of their relapses were detected. Of 7 patients with
      postsuicidal manic switching, 4 (57%) experienced a switch-down into depression.
      CONCLUSION: This study suggests that unipolar depression is significantly
      improved after attempted suicide, but also that depressed patients showing
      postsuicidal improvement or manic switching are likely to undergo relapse or
      switch-down into depression within a short period.

PMID- 14658971
TI  - Trajectories of posttraumatic stress disorder following myocardial infarction: a
      prospective study.
AB  - BACKGROUND: This study examines the trajectories of posttraumatic stress disorder
      (PTSD) following myocardial infarction (MI). More specifically, it has 2 aims:
      (1) to examine whether the trajectory of PTSD is predicted by level of threat and
      the nature of initial reactions and (2) to examine the associations between the
      trajectory of PTSD and anxiety, somatization, health-related quality of life, and
      hospitalization 7 months following MI. METHOD: 116 MI patients were examined
      twice. At time 1, within a week of the patient's MI, acute stress disorder (ASD)
      was assessed and medical measures were obtained from patients' hospital records.
      At time 2, 7 months later, PTSD, anxiety, physical residuals, and health-related
      quality of life were assessed. Data were gathered in 1999. RESULTS: Six percent
      of the respondents had both ASD and PTSD, 10% did not have ASD but did have PTSD,
      and 12% had ASD but not PTSD. The trajectory of PTSD was associated with severity
      of anxiety, somatic complaints, and health-related quality of life. In addition,
      while the severity of MI did not predict the trajectory of PTSD, the perceived
      severity did. Patients without PTSD but with prior ASD did not differ in their
      initial reactions from those without ASD. CONCLUSION: These findings provide
      support for the considerable variability in the trajectory of the development of
      PTSD and suggest that although ASD is associated with subsequent PTSD, the
      predictive role of initial reactions is limited.

PMID- 14658972
TI  - Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in
      patients with major depression and insomnia.
AB  - BACKGROUND: Sleep complaints are common in patients with major depressive
      disorder (MDD). Both MDD and antidepressant drugs characteristically alter
      objective sleep measures. This study compares the effects of mirtazapine and
      fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia.
      METHOD: Patients (N = 19) received initial baseline polysomnography evaluations
      over 2 consecutive nights. Subjects were randomly assigned to either fluoxetine
      (20-40 mg/day) or mirtazapine (15-45 mg/day) treatment for an 8-week, double
      blind, double-dummy treatment trial. Single-night polysomnograms were conducted
      at weeks 1, 2, and 8, with depression ratings assessed at baseline and weeks 1,
      2, 3, 4, 6, and 8. Statistical analysis was performed by repeated-measures
      analysis of variance followed by Dunnet's post hoc analyses. RESULTS: Patients
      receiving mirtazapine (N = 8) had significant improvement in objective sleep
      physiology measures at 8 weeks. Improvements in sleep latency, sleep efficiency,
      and wake after sleep onset were significant after only 2 weeks of mirtazapine
      treatment. No significant changes in sleep continuity measures were observed in
      the fluoxetine group (N = 11). Both groups improved clinically in mood and
      subjective sleep measures from baseline, with no differences between groups.
      CONCLUSION: These data demonstrate the differential effects of mirtazapine and
      fluoxetine, with significant improvement in favor of mirtazapine, on objective
      sleep parameters in MDD patients with insomnia.

PMID- 14658973
TI  - Mental health treatment received by primary care patients with posttraumatic
      stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is receiving growing attention
      as a pervasive and impairing disorder but is still undertreated. Our purpose was
      to describe the characteristics of mental health treatment received by primary
      care patients diagnosed with PTSD. METHOD: 4383 patients from 15 primary care,
      family practice, or internal medicine clinics were screened for anxiety symptoms
      using a self-report questionnaire developed for the study. Those found positive
      for anxiety symptoms (N = 539) were interviewed with the Structured Clinical
      Interview for DSM-IV. Of these patients, 197 met diagnostic criteria for PTSD and
      were examined in the present study regarding the rates and types of mental health
      treatment they were currently receiving. Data were gathered from July 1997 to May
      2001. RESULTS: Nearly half (48%) of the patients in general medical practice with
      PTSD were receiving no mental health treatment at the time of intake to the
      study. Of those receiving treatment, psychopharmacologic interventions were most
      common. Few patients were receiving empirically supported psychosocial
      interventions. Current comorbid major depressive disorder and current comorbid
      panic disorder with agoraphobia were significantly associated with receiving
      mental health treatment (major depressive disorder, p <.10; panic disorder with
      agoraphobia, p <.05). The most common reason patients gave for not receiving
      medication was the failure of physicians to recommend such treatment, which was
      also among the most common reasons for not receiving psychosocial treatment.
      CONCLUSIONS: Despite the morbidity, psychosocial impairment, and distress
      associated with PTSD, substantial proportions of primary care patients with the
      disorder are going untreated or are receiving inadequate treatment. Results
      suggest a need for better identification and treatment of PTSD in the primary
      care setting.

PMID- 14658974
TI  - Duloxetine in the long-term treatment of major depressive disorder.
AB  - BACKGROUND: Depression is a chronic recurring disorder and guidelines recommend
      long-term therapy. This clinical trial evaluated the long-term (1 year) safety
      and efficacy of duloxetine, a dual reuptake inhibitor of serotonin and
      norepinephrine, in patients with DSM-IV major depressive disorder. METHOD: This
      was an open-label, 52-week, multinational clinical trial in outpatients (age > or
      = 18 years) who received duloxetine at 80 mg/day (administered 40 mg twice daily)
      to 120 mg/day (administered 60 mg twice daily) for up to 1 year. RESULTS: A total
      of 1279 patients had postbaseline data. Of these, 520 were exposed to duloxetine
      for at least 360 days, yielding approximately 808 patient-years of total
      exposure. Mean changes in Clinical Global Impressions-Severity of Illness scale
      (CGI-S) score, 17-item Hamilton Rating Scale for Depression total score and
      subfactor scores, Beck Depression Inventory-II score, and Sheehan Disability
      Scale score and mean Patient Global Impression-Improvement scale (PGI-I) scores
      all showed highly significant (p <.001) improvements at all assessment times. The
      estimated probabilities of improvement in CGI-S and PGI-I scores at week 1 were
      40.4% and 59.2%, respectively, and at week 2 were 70.0% and 78.3%. The estimated
      probabilities of remission at weeks 6, 28, and 52 were 50.8%, 75.6%, and 81.8%,
      respectively. Adverse events led to discontinuation in 218 patients (17.0%). The
      most frequent specific events leading to discontinuation were nausea (1.5%),
      somnolence (1.4%), vomiting (0.9%), hypomania (0.8%), pregnancy (0.8%), dizziness
      (0.6%), insomnia (0.6%), and hypertension (0.5%). Treatment-emergent adverse
      events that were reported by > 10% of patients included nausea, insomnia,
      headache, somnolence, dry mouth, dizziness, constipation, sweating increase,
      anxiety, diarrhea, and fatigue. Most events occurred early in the study. Of those
      events that first occurred or worsened after discontinuation, only dizziness
      (8.3%) occurred in more than 5% of patients. Mean changes from baseline to last
      observation for standing and supine pulse were less than 2 b.p.m. Mean changes in
      blood pressure (< 1.0 mm Hg), corrected QT interval (< 1 msec), and body weight
      (2.4 kg [5.3 lb]) were not clinically significant. Laboratory analyses varied
      across visits, and mean changes after 52 weeks were generally close to zero. The
      incidence of laboratory values above or below normal limits at any time during
      treatment was low. CONCLUSION: Duloxetine was effective, safe, and well tolerated
      in the long-term treatment of major depression at a dose of 80 to 120 mg/day in
      this study.

PMID- 14658975
TI  - Tiagabine for the treatment of generalized anxiety disorder: a randomized, open
      label, clinical trial with paroxetine as a positive control.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA) plays a central role in the
      pathophysiology of anxiety. Tiagabine, a selective GABA reuptake inhibitor,
      enhances normal GABA tone. This 10-week, randomized, open-label trial evaluated
      tiagabine in patients with generalized anxiety disorder (GAD), with paroxetine
      serving as a positive control. METHOD: Adult patients with DSM-IV GAD were
      randomly assigned to receive either tiagabine or paroxetine. Tiagabine was
      initiated at 4 mg/day (2 mg morning and evening) during week 1. Between weeks 2
      and 6, the dose was individually titrated in 2-mg increments (maximum increase of
      4 mg/week) for optimal response to a maximum dose of 16 mg/day (8 mg morning and
      evening). During weeks 7 through 10, patients received the dosage determined
      during the titration period. Paroxetine was initiated at 20 mg nightly for the
      first week and similarly titrated in 10-mg increments to a maximum dose of 60
      mg/day. Assessments included the Hamilton Rating Scale for Anxiety (HAM-A),
      Hospital Anxiety and Depression Scale (HADS), Hamilton Rating Scale for
      Depression (HAM-D), Pittsburgh Sleep Quality Index (PSQI), and Sheehan Disability
      Scale (SDS). RESULTS: Forty patients were enrolled (tiagabine, N = 20;
      paroxetine, N = 20). Mean final doses were tiagabine 10 mg/day (range, 4-16
      mg/day) or paroxetine 27 mg/day (range, 20-40 mg/day). Tiagabine and paroxetine
      significantly reduced anxiety (HAM-A and HADS total and anxiety subscales).
      Although patients were not diagnosed with a mood disorder, both tiagabine and
      paroxetine reduced comorbid depressive symptoms (HAM-D total and HADS total and
      depressive subscale). Tiagabine and paroxetine significantly improved sleep
      quality (PSQI) and functioning (SDS). Both tiagabine and paroxetine were well
      tolerated. CONCLUSION: The selective GABA reuptake inhibitor tiagabine and the
      positive control paroxetine significantly reduced anxiety and comorbid depressive
      symptoms, improved sleep quality and functioning, and were well tolerated in
      patients with GAD. Tiagabine may be a therapeutic option for the treatment of
      anxiety disorders.

PMID- 14658977
TI  - Olanzapine for self-injurious, aggressive, and disruptive behaviors in
      intellectually disabled adults: a retrospective, open-label, naturalistic trial.
AB  - BACKGROUND: The effectiveness of olanzapine in treating challenging behaviors in
      the intellectually disabled and its ability to substitute for conventional
      antipsychotic drugs were evaluated. METHOD: A total of 20 institutionalized
      adults with a mean age of 42.7 years (range, 18-55 years) with intellectual
      disability and aggression, self-injurious behavior, destructive/disruptive
      behavior, or combinations of these behaviors were studied. These individuals were
      receiving multiple psychotropic medications at baseline and were given additional
      treatment with the atypical antipsychotic agent olanzapine. The mean dose of
      olanzapine was 9.1 mg/day (range, 2.5-22.5 mg/day). Effectiveness was determined
      by retrospective review of the summaries of quarterly neuropsychiatric behavioral
      reviews and retrospective review of longitudinal behavioral graphs of target
      symptoms. Data were collected from 1995 to 2000. RESULTS: A significant decrease
      in global challenging behaviors and specific target behaviors (i.e., aggression,
      self-injurious behaviors, destructive/disruptive behaviors) occurred (p <.05). A
      numerical decrease in the dosage of concurrent conventional antipsychotic
      medications occurred over the course of the first 6 months of olanzapine therapy,
      and a statistically significant (p <.005) decrease from the start of olanzapine
      therapy occurred in those subjects who received olanzapine for longer than 6
      months (mean = 20.3 months). A significant increase in weight occurred in the
      subject group during the first 6 months of olanzapine treatment (p <.006), and
      sedation and constipation were the other common side effects noted. CONCLUSIONS:
      Olanzapine was found to be effective in the treatment of challenging behaviors in
      the intellectually disabled and in part could be substituted for administration
      of conventional antipsychotic drugs.

PMID- 14658976
TI  - Treatment of schizophrenia with long-acting injectable risperidone: a 12-month
      open-label trial of the first long-acting second-generation antipsychotic.
AB  - BACKGROUND: The long-term safety and efficacy of long-acting injectable
      risperidone, the first long-acting second-generation antipsychotic, were
      evaluated in stable patients with schizophrenia. METHOD: After a 2-week run-in
      period during which patients with DSM-IV schizophrenia received flexible doses of
      1 to 6 mg of oral risperidone, patients received injections of 25 mg, 50 mg, or
      75 mg of long-acting risperidone every 2 weeks for 12 months. Severity of
      extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale
      (ESRS), and efficacy was assessed with the Positive and Negative Syndrome Scale
      (PANSS). This study was conducted from March 29, 1999 to July 19, 2000. RESULTS:
      The subjects were 615 patients with schizophrenia who received at least 1
      injection of long-acting risperidone. The 12-month trial was completed by 65% of
      patients. Treatment was discontinued because of adverse events in 5% of patients.
      Extrapyramidal symptoms as adverse events were reported by 25% of the patients.
      Severity of extrapyramidal symptoms (according to ESRS scores) was low at
      baseline and decreased in each of the groups during the 12 months. The other most
      common adverse events were anxiety in 24%, insomnia in 21%, psychosis in 17%, and
      depression in 14% of the patients. Little pain was associated with the
      injections. Severity of symptoms of schizophrenia was improved in each group,
      with significant reductions in PANSS total scores (p <.01) and positive (p <.01)
      and negative (p <.001) factor scores. CONCLUSION: In terms of both safety and
      efficacy, symptomatically stable patients with schizophrenia benefit from being
      switched to long-acting injectable risperidone.

PMID- 14658978
TI  - Divalproex versus olanzapine in mania.

PMID- 14658980
TI  - Worsening of psychosis after replacement of adjunctive valproate with topiramate
      in a schizophrenia patient.

PMID- 14658981
TI  - Effect of bupropion on sexual dysfunction induced by fluoxetine: a case report of
      hypersexuality.

PMID- 14658982
TI  - A word of caution about the implied role for duloxetine in pain management.

PMID- 14658983
TI  - Introduction: treating depression and anxiety to remission.

PMID- 14658985
TI  - Treating depression to remission.
AB  - Over the last several years, the recommended end point in the treatment of
      depression has become remission. Patients who achieve remission not only enjoy
      the benefits of decreased disability and improved functioning in work, family,
      and social situations, they also have a lower risk of disease progression and
      relapse. Despite the benefits associated with remission, many patients are left
      with residual symptoms that prevent them from achieving these benefits. Potential
      obstacles to reaching remission include diagnostic issues, inadequate treatment,
      lack of adherence to the treatment regimen, satisfaction with partial
      improvement, and failure to recognize residual symptoms. Strategies for treating
      to remission include ensuring appropriate diagnosis, setting treatment goals,
      selecting antidepressants that are more likely to result in remission, providing
      patient education and adequate treatment, assessing for residual symptoms, and
      heeding partial response or lack of response by switching or augmenting
      treatment.

PMID- 14658986
TI  - Prevention of relapse and recurrence in depression: the role of long-term
      pharmacotherapy and psychotherapy.
AB  - Major depressive disorder is a chronic disorder, frequently characterized by
      relapses and recurrences. One of the major risk factors for additional episodes
      of depression is the presence of residual symptoms that persist after a
      depressive episode ends; these residual symptoms tend to progress to another
      depressive episode. Although relapse or recurrence may be prevented with long
      term pharmacotherapy, this approach is recommended only for patients at high risk
      of relapse or recurrence. Patients not at high risk who are effectively treated
      to full remission have a substantially lower risk of developing another
      depressive episode. In addition, psychotherapy, alone or combined with
      medication, has been shown to be effective in preventing further episodes of
      depression.

PMID- 14658987
TI  - Gender-specific considerations in the treatment of mood disorders in women across
      the life cycle.
AB  - Major depressive disorder in women is a significant health concern. Rates of
      depression in women are approximately twice those seen in men. Observations of
      gender-based differences in prevalence, presentation, and treatment response in
      depression raise questions about the underlying causes of such differences. In
      addition, the specific factors that predict vulnerability to reproductive
      associated mood disturbance, including premenstrual dysphoric disorder,
      postpartum depression, and perimenopausal mood disturbance, remain to be
      delineated. While a growing amount of controlled data is emerging that describes
      response to treatment in women who suffer from these disorders, further
      investigation is needed to identify subgroups of women who are most at risk for
      depression and to define the most effective treatments for these patients.

PMID- 14658989
TI  - Attending to anxiety disorders in primary care.
AB  - Anxiety disorders are highly prevalent among patients in primary care. These
      conditions can be disabling and costly to the patient and to the health care
      system. Despite the prevalence of anxiety disorders, however, patients often
      remain undiagnosed and untreated, and patients with unrecognized anxiety
      disorders tend to be high users of general medical care. Diagnosis may be
      complicated by the typical presentation in primary care; patients with anxiety
      disorders may present with multiple somatic complaints and comorbid disorders,
      causing great effort and expense in identifying the cause of unexplained
      symptoms. Once anxiety disorders are identified, patients may be treated using
      well-tested and efficacious psychosocial and pharmacologic treatments. It is
      therefore important for primary care physicians to recognize and treat patients
      with anxiety disorders.

PMID- 14658990
TI  - Establishment of remission criteria for anxiety disorders.
AB  - Anxiety disorders such as generalized anxiety disorder, social anxiety disorder,
      panic disorder, and posttraumatic stress disorder are typically chronic
      conditions associated with high health care costs and are often accompanied by
      psychiatric comorbidity, including major depressive disorder, substance abuse,
      and other anxiety disorders. Anxiety disorders are associated with significant
      functional impairment in social, vocational, and familial spheres and with
      diminished overall quality of life. The following clinical overview provides
      informal guidelines for identifying remission in patients with an anxiety
      disorder. A systematic approach to treatment that includes patient education,
      encouragement of exposure, attention to relevant comorbidities, use of
      empirically proven pharmacotherapies, and psychosocial interventions of adequate
      intensity and duration will improve outcomes and move patients toward marked
      improvement and remission.

PMID- 14658991
TI  - Effects of intensive voice treatment (the Lee Silverman Voice Treatment [LSVT])
      on ataxic dysarthria: a case study.
AB  - This study examined the effects of intensive voice treatment (the Lee Silverman
      Voice Treatment [LSVT]) on ataxic dysarthria in a woman with cerebellar
      dysfunction secondary to thiamine deficiency. Perceptual and acoustic measures
      were made on speech samples recorded just before the LSVT program was
      administered, immediately after it was administered, and at 9 months follow-up.
      Results indicate short- and long-term improvement in phonatory and articulatory
      functions, speech intelligibility, and overall communication and job-related
      activity following LSVT. This study's findings provide initial support for the
      application of LSVT to the treatment of speech disorders accompanying ataxic
      dysarthria. Potential neural mechanisms that may underlie the effects of loud
      phonation and LSVT are addressed.

PMID- 14658992
TI  - Neuromuscular treatments for speech and swallowing: a tutorial.
AB  - Despite the proliferation of oral motor therapies, much controversy exists
      regarding the application and benefit of neuromuscular treatments (NMTs) such as
      strength training for alleviating dysarthria and/or dysphagia. Not only is
      limited empirical support available to validate the use of NMTs, but clinicians
      may also lack the foundational information needed to judge the theoretical
      soundness of unstudied treatment strategies. This tutorial reviews the
      theoretical foundations for several NMTs, including active exercises, passive
      exercises, and physical modalities. It highlights how these techniques have been
      used to address neuromuscular impairments in the limb musculature and explores
      potential applications to the speech and swallowing musculature. Key issues
      discussed in relation to active exercise are the selection of treatment targets
      (e.g., strength, endurance, power, range of motion), specificity of training,
      progression, and recovery. Factors influencing the potential effectiveness of
      passive exercises and physical modalities are presented, along with discussion of
      additional issues contributing to the controversy surrounding oral motor
      therapies.

PMID- 14658993
TI  - Effects of voicing and syntactic complexity on sign expression in adductor
      spasmodic dysphonia.
AB  - Clients with adductor spasmodic dysphonia (ADSD) tend to exhibit inter- and
      intraclient variability of signs and symptoms. This variability may result in
      inaccurate assessment of severity. Accurate assessment of severity requires
      knowledge concerning the factors that affect the expression of ADSD signs and
      symptoms. This study examined ADSD sign expression as a function of voicing and
      syntactic complexity. Fifteen ADSD participants and 15 control participants
      completed a task consisting of 30 sentences. ADSD signs were significantly more
      frequent in predominantly voiced sentences than in predominantly voiceless
      sentences, regardless of level of syntactic complexity. Center-embedded sentences
      comprising predominantly voiced consonants were found to evoke the greatest
      number of ADSD signs. These results have important implications for the
      assessment of ADSD.

PMID- 14658994
TI  - The relationship of self-efficacy and depression to stuttering.
AB  - This study investigated the relationship of self-efficacy for verbal fluency,
      academic self-efficacy, and depression between adolescents who stutter and fluent
      speakers. Two separate discriminant function analyses were performed. The first
      analysis used the self-efficacy and depression scores as response variables and
      fluency classification as the grouping variable. Results indicated that self
      efficacy for speech was the sole significant variable and accounted for 61% of
      the variance in group status. A second simplified discriminant function analysis
      was performed using speech self-efficacy as the sole predictor of group
      membership. This single discriminant function correctly classified 81% of the
      overall sample into their known groups. Further, classification for participants
      who did not stutter (95.2%) was better than for those who did stutter (67%).
      Based on this and earlier research, adolescents appear to be capable of using
      self-efficacy scaling as a measure of confidence for verbal fluency, which may
      eventually prove to be useful in treatment.

PMID- 14658995
TI  - Telehealth: voice therapy using telecommunications technology.
AB  - Telehealth offers the potential to meet the needs of underserved populations in
      remote regions. The purpose of this study was a proof-of-concept to determine
      whether voice therapy can be delivered effectively remotely. Treatment outcomes
      were evaluated for a vocal rehabilitation protocol delivered under 2 conditions:
      with the patient and clinician interacting within the same room (conventional
      group) and with the patient and clinician in separate rooms, interacting in real
      time via a hard-wired video camera and monitor (video teleconference group).
      Seventy-two patients with voice disorders served as participants. Based on
      evaluation by otolaryngologists, 31 participants were diagnosed with vocal
      nodules, 29 were diagnosed with edema, 9 were diagnosed with unilateral vocal
      fold paralysis, and 3 presented with vocal hyperfunction with no laryngeal
      pathology. Fifty-one participants (71%) completed the vocal rehabilitation
      protocol. Outcome measures included perceptual judgments of voice quality,
      acoustic analyses of voice, patient satisfaction ratings, and fiber-optic
      laryngoscopy. There were no differences in outcome measures between the
      conventional group and the remote video teleconference group. Participants in
      both groups showed positive changes on all outcome measures after completing the
      vocal rehabilitation protocol. Reasons for participants discontinuing therapy
      prematurely provided support for the telehealth model of service delivery.

PMID- 14658996
TI  - Connected speech intelligibility of children with cochlear implants and children
      with normal hearing.
AB  - The objective of this study was to compare the connected speech intelligibility
      of children who use cochlear implants with that of children who have normal
      hearing. Previous research has shown that speech intelligibility improves from
      before cochlear implantation to after implantation and that the speech
      intelligibility of children who use cochlear implants compares favorably with
      that of children who use conventional hearing aids. However, no research has yet
      addressed the question of how the speech intelligibility of children who use
      cochlear implants compares to that of children with normal hearing. In the
      current study, archival data on connected speech intelligibility from 51 children
      with cochlear implants were compared with newly collected data from 47 children
      with normal hearing. Results showed that for children with cochlear implants,
      greater intelligibility was associated with both increased chronological age and
      increased duration of cochlear implant use. Consistent with previous studies,
      children with normal hearing achieved adult-like or near-adult-like
      intelligibility around the age of 4 years, but a similar peak in intelligibility
      was not observed for the children who used cochlear implants. On the whole,
      children with cochlear implants were significantly less intelligible than
      children with normal hearing, when controlling both for chronological age and for
      length of auditory experience. These results have implications for the
      socialization and education of children with cochlear implants, particularly with
      respect to on-time placement in mainstream educational environments with age
      peers.

PMID- 14658997
TI  - Mexican-American and Anglo-American mothers' beliefs and values about child
      rearing, education, and language impairment.
AB  - This study investigated the cross-cultural and intra cultural diversity of
      mothers' beliefs and values regarding child rearing, education, and the causes of
      language impairment. Thirty Mexican-American and 30 Anglo-American mothers of
      children with language impairments completed 2 questionnaires, and 10 randomly
      selected mothers from each group participated in an interview. In addition, the
      Mexican-American mothers completed an acculturation rating scale. Results
      indicated that Mexican-American mothers held more strongly traditional,
      authoritarian, and conforming educational and child rearing beliefs and values
      than Anglo-American mothers. Mexican-American mothers cited extrinsic attributes
      as the cause of their children's language impairment, whereas Anglo-American
      mothers cited intrinsic attributes. Mexican-American mothers exhibited
      differences in their beliefs that were related to their level of acculturation to
      the mainstream culture.

PMID- 14658998
TI  - Phonological awareness and phonemic perception in 4-year-old children with
      delayed expressive phonology skills.
AB  - The purpose of this study was to compare the phonological awareness abilities of
      2 groups of 4-year-old children: one with normally developing speech and language
      skills and the other with moderately or severely delayed expressive phonological
      skills but age-appropriate receptive vocabulary skills. Each group received tests
      of articulation, receptive vocabulary, phonemic perception, early literacy, and
      phonological awareness skills. The groups were matched for receptive language
      skills, age, socioeconomic status, and emergent literacy knowledge. The children
      with expressive phonological delays demonstrated significantly poorer phonemic
      perception and phonological awareness skills than their normally developing
      peers. The results suggest that preschool children with delayed expressive
      phonological abilities should be screened for their phonological awareness skills
      even when their language skills are otherwise normally developing.

PMID- 14658999
TI  - Does physical training increase insulin sensitivity in chronic heart failure
      patients?
AB  - To determine the effect of training on insulin sensitivity (IS) and how this
      relates to peak V(.)O(2) (peak oxygen uptake) in CHF (chronic heart failure), 77
      CHF patients (New York Heart Association class, II/III; men/women, 59/18; age,
      60+/-9 years; body mass index, 26.7+/-3.9 kg/m(2); left ventricular ejection
      fraction, 26.9+/-8.1%; expressed as means+/-S.D.) participated in the study.
      Patients were randomly assigned to a training or control group (TrG or CG
      respectively). Sixty-one patients completed the study. Patients participated in
      training (combined strength and endurance exercises) four times per week, two
      times supervised and two times at home. Before and after intervention,
      anthropometry, IS (euglycaemic hyperinsulinaemic clamp) and peak V(.)O(2)
      (incremental cycle ergometry) were assessed. Intervention did not affect IS
      significantly, even though IS increased by 20% in TrG and 11% in CG (not
      significant). Peak V(.)O(2) increased as a result of training (6% increase in
      TrG; 2% decrease in CG; P <0.05). In both groups (TrG and CG), the change in IS
      correlated positively with the change in peak V(.)O(2) ( r =0.30, P <0.05).
      Training resulted in an increase in peak V(.)O(2), but not in IS. Whether
      physical training actually increases IS in CHF patients remains unclear.

PMID- 14659000
TI  - Sigma54-dependent transcription activator phage shock protein F of Escherichia
      coli: a fragmentation approach to identify sequences that contribute to self
      association.
AB  - Proteins that belong to the AAA (ATPases associated with various cellular
      activities) superfamily of mechanochemical enzymes are versatile and control a
      wide array of cellular functions. Many AAA proteins share the common property of
      self-association into oligomeric structures and use nucleotide binding and
      hydrolysis to regulate their biological output. The Escherichia coli
      transcription activator PspF (phage shock protein F) is a member of the sigma54
      dependent transcriptional activators that belong to the AAA protein family.
      Nucleotide interactions condition the functional state of PspF, enabling it to
      self-associate and interact with its target, the sigma54-RNAP (RNA polymerase)
      closed complex. The self-association determinants within the AAA domain of
      sigma54-dependent activators remain poorly characterized. In the present study,
      we have used a fragment of the AAA domain of PspF as a probe to study the
      nucleotide-conditioned self-association of PspF. Results show that the PspF
      fragment acts in trans to inhibit specifically self-association of PspF. The PspF
      fragment prevented efficient binding of nucleotides to PspF, consistent with the
      observation that the site for nucleotide interactions within an oligomer of AAA
      proteins is created between two protomers. Using proximity-based footprinting and
      cross-linking techniques, we demonstrate that the sequences represented in this
      fragment are close to one protomer-protomer interface within a PspF oligomer. As
      the sequences represented in this PspF fragment also contain a highly conserved
      motif that interacts with the sigma54-RNAP closed complex, we suggest that PspF
      may be organized to link nucleotide interactions and self-association to sigma54
      RNAP binding and transcription activation.

PMID- 14659005
TI  - For the good of the state.
AB  - Recent advances in biology and medicine, from the sequence of the human genome to
      the cloning of mammals have made many lay people profoundly uneasy about the
      future of humanity.

PMID- 14659004
TI  - Endophilins interact with Moloney murine leukemia virus Gag and modulate virion
      production.
AB  - BACKGROUND: The retroviral Gag protein is the central player in the process of
      virion assembly at the plasma membrane, and is sufficient to induce the formation
      and release of virus-like particles. Recent evidence suggests that Gag may co-opt
      the host cell's endocytic machinery to facilitate retroviral assembly and
      release. RESULTS: A search for novel partners interacting with the Gag protein of
      the Moloney murine leukemia virus (Mo-MuLV) via the yeast two-hybrid protein
      protein interaction assay resulted in the identification of endophilin 2, a
      component of the machinery involved in clathrin-mediated endocytosis. We
      demonstrate that endophilin interacts with the matrix or MA domain of the Gag
      protein of Mo-MuLV, but not of human immunodeficiency virus, HIV. Both
      exogenously expressed and endogenous endophilin are incorporated into Mo-MuLV
      viral particles. Titration experiments suggest that the binding sites for
      inclusion of endophilin into viral particles are limited and saturable. Knock
      down of endophilin with small interfering RNA (siRNA) had no effect on virion
      production, but overexpression of endophilin and, to a lesser extent, of several
      fragments of the protein, result in inhibition of Mo-MuLV virion production, but
      not of HIV virion production. CONCLUSIONS: This study shows that endophilins
      interact with Mo-MuLV Gag and affect virion production. The findings imply that
      endophilin is another component of the large complex that is hijacked by
      retroviruses to promote virion production.

PMID- 14659006
TI  - Multi-species sequence comparison: the next frontier in genome annotation.
AB  - Multi-species comparisons of DNA sequences are more powerful for discovering
      functional sequences than pairwise DNA sequence comparisons. Most current
      computational tools have been designed for pairwise comparisons, and efficient
      extension of these tools to multiple species will require knowledge of the ideal
      evolutionary distance to choose and the development of new algorithms for
      alignment, analysis of conservation, and visualization of results.

PMID- 14659007
TI  - Toward an understanding of the structural basis of translation.
AB  - The recently solved X-ray crystal structures of the ribosome have provided
      opportunities for studying the molecular basis of translation with a variety of
      methods including cryo-electron microscopy - where maps give the first glimpses
      of ribosomal evolution - and fluorescence spectroscopy techniques.

PMID- 14659008
TI  - The draft genome sequence of the nematode Caenorhabditis briggsae, a companion to
      C. elegans.
AB  - The publication of the draft genome sequence of Caenorhabditis briggsae improves
      the annotation of the genome of its close relative Caenorhabditis elegans and
      will facilitate comparative genomics and the study of the evolutionary changes
      during development.

PMID- 14659009
TI  - Signaling advances from immunogenetics to immunogenomics.
AB  - Recent studies describe new genome-wide mutagenesis strategies, coupled with
      phenotypic screening, and demonstrate the power of such approaches to provide new
      insights into the genetics of the immune response.

PMID- 14659010
TI  - Localizing the proteome.
AB  - The subcellular localization of the entire proteome of an organism, the yeast
      Saccharomyces cerevisiae, has been revealed for the first time. Comparison with
      less comprehensive studies of mammalian cells provides insights into the
      localization of the mammalian proteome.

PMID- 14659012
TI  - Finding the functional gems in plant genomes.
AB  - A report on the joint second Plant Genomics European Meeting (Plant GEMs) and
      fourth Genomic Arabidopsis Resource Network (GARNet) meeting, York, UK, 3-6
      September 2003.

PMID- 14659011
TI  - Genetics and functional genomics of type 2 diabetes mellitus.
AB  - Genome-wide studies of transcription in the skeletal muscle of type 2 diabetic
      patients have identified coordinated changes in the expression of genes involved
      in oxidative phosphorylation, and have underlined the central role of the
      oxidative-phosphorylation regulator, PCG1alpha. These findings help unravel the
      complex pathogenesis and inheritance of polygenic type 2 diabetes mellitus.

PMID- 14659013
TI  - MGED comes of age.
AB  - A report on the Sixth International Meeting of the Microarray Gene Expression
      Data Society ('MGED6'), Aix-en-Provence, France, 6-8 September 2003.

PMID- 14659014
TI  - Yeast functional genomics and cell biology: no longer in the dark.
AB  - A report on the Cold Spring Harbor Laboratory meeting 'Yeast Cell Biology', Cold
      Spring Harbor, USA, 12-17 August 2003.

PMID- 14659015
TI  - Expressed sequence tag analysis in Cycas, the most primitive living seed plant.
AB  - BACKGROUND: Cycads are ancient seed plants (living fossils) with origins in the
      Paleozoic. Cycads are sometimes considered a 'missing link' as they exhibit
      characteristics intermediate between vascular non-seed plants and the more
      derived seed plants. Cycads have also been implicated as the source of 'Guam's
      dementia', possibly due to the production of S(+)-beta-methyl-alpha, beta
      diaminopropionic acid (BMAA), which is an agonist of animal glutamate receptors.
      RESULTS: A total of 4,200 expressed sequence tags (ESTs) were created from Cycas
      rumphii and clustered into 2,458 contigs, of which 1,764 had low-stringency BLAST
      similarity to other plant genes. Among those cycad contigs with similarity to
      plant genes, 1,718 cycad 'hits' are to angiosperms, 1,310 match genes in
      gymnosperms and 734 match lower (non-seed) plants. Forty-six contigs were found
      that matched only genes in lower plants and gymnosperms. Upon obtaining the
      complete sequence from the clones of 37/46 contigs, 14 still matched only
      gymnosperms. Among those cycad contigs common to higher plants, ESTs were
      discovered that correspond to those involved in development and signaling in
      present-day flowering plants. We purified a cycad EST for a glutamate receptor
      (GLR)-like gene, as well as ESTs potentially involved in the synthesis of the GLR
      agonist BMAA. CONCLUSIONS: Analysis of cycad ESTs has uncovered conserved and
      potentially novel genes. Furthermore, the presence of a glutamate receptor
      agonist, as well as a glutamate receptor-like gene in cycads, supports the
      hypothesis that such neuroactive plant products are not merely herbivore
      deterrents but may also serve a role in plant signaling.

PMID- 14659016
TI  - Expressed sequence tag profiling identifies developmental and anatomic
      partitioning of gene expression in the mouse prostate.
AB  - BACKGROUND: The prostate gland is an organ with highly specialized functional
      attributes that serves to enhance the fertility of mammalian species. Much of the
      information pertaining to normal and pathological conditions affecting the
      prostate has been obtained through extensive developmental, biochemical and
      genetic analyses of rodent species. Although important insights can be obtained
      through detailed anatomical and histological assessments of mouse and rat models,
      further mechanistic explanations are greatly aided through studies of gene and
      protein expression. RESULTS: In this article we characterize the repertoire of
      genes expressed in the normal developing mouse prostate through the analysis of
      50,562 expressed sequence tags derived from 14 mouse prostate cDNA libraries.
      Sequence assemblies and annotations identified 15,009 unique transcriptional
      units of which more than 600 represent high quality assemblies without
      corresponding annotations in public gene expression databases. Quantitative
      analyses demonstrate distinct anatomical and developmental partitioning of
      prostate gene expression. This finding may assist in the interpretation of
      comparative studies between human and mouse and guide the development of new
      transgenic murine disease models. The identification of several novel genes is
      reported, including a new member of the beta-defensin gene family with prostate
      restricted expression. CONCLUSIONS: These findings suggest a potential role for
      the prostate as a defensive barrier for entry of pathogens into the genitourinary
      tract and, further, serve to emphasize the utility of the continued evaluation of
      transcriptomes from a diverse repertoire of tissues and cell types.

PMID- 14659017
TI  - Comparison of the canine and human olfactory receptor gene repertoires.
AB  - BACKGROUND: Olfactory receptors (ORs), the first dedicated molecules with which
      odorants physically interact to arouse an olfactory sensation, constitute the
      largest gene family in vertebrates, including around 900 genes in human and 1,500
      in the mouse. Whereas dogs, like many other mammals, have a much keener olfactory
      potential than humans, only 21 canine OR genes have been described to date.
      RESULTS: In this study, 817 novel canine OR sequences were identified, and 640
      have been characterized. Of the 661 characterized OR sequences, representing half
      of the canine repertoire, 18% are predicted to be pseudogenes, compared with 63%
      in human and 20% in mouse. Phylogenetic analysis of 403 canine OR sequences
      identified 51 families, and radiation-hybrid mapping of 562 showed that they are
      distributed on 24 dog chromosomes, in 37 distinct regions. Most of these regions
      constitute clusters of 2 to 124 closely linked genes. The two largest clusters
      (124 and 109 OR genes) are located on canine chromosomes 18 and 21. They are
      orthologous to human clusters located on human chromosomes 11q11-q13 and
      HSA11p15, containing 174 and 115 ORs respectively. CONCLUSIONS: This study shows
      a strongly conserved genomic distribution of OR genes between dog and human,
      suggesting that OR genes evolved from a common mammalian ancestral repertoire by
      successive duplications. In addition, the dog repertoire appears to have expanded
      relative to that of humans, leading to the emergence of specific canine OR genes.

PMID- 14659018
TI  - New connections in the prokaryotic toxin-antitoxin network: relationship with the
      eukaryotic nonsense-mediated RNA decay system.
AB  - BACKGROUND: Several prokaryotic plasmids maintain themselves in their hosts by
      means of diverse post-segregational cell killing systems. Recent findings suggest
      that chromosomally encoded copies of toxins and antitoxins of post-segregational
      cell killing systems - such as the RelE system - might function as regulatory
      switches under stress conditions. The RelE toxin cleaves ribosome-associated
      transcripts, whereas another post-segregational cell killing toxin, ParE,
      functions as a gyrase inhibitor. RESULTS: Using sequence profile analysis we were
      able unify the RelE- and ParE-type toxins with several families of small,
      uncharacterized proteins from diverse bacteria and archaea into a single
      superfamily. Gene neighborhood analysis showed that the majority of these
      proteins were encoded by genes in characteristic neighborhoods, in which genes
      encoding toxins always co-occurred with genes encoding transcription factors that
      are also antitoxins. The transcription factors accompanying the RelE/ParE
      superfamily may belong to unrelated or distantly related superfamilies, however.
      We used this conserved neighborhood template to transitively search genomes and
      identify novel post-segregational cell killing-related systems. One of these
      novel systems, observed in several prokaryotes, contained a predicted toxin with
      a PilT-N terminal (PIN) domain, which is also found in proteins of the eukaryotic
      nonsense-mediated RNA decay system. These searches also identified novel
      transcription factors (antitoxins) in post-segregational cell killing systems.
      Furthermore, the toxin Doc defines a potential metalloenzyme superfamily, with
      novel representatives in bacteria, archaea and eukaryotes, that probably acts on
      nucleic acids. CONCLUSIONS: The tightly maintained gene neighborhoods of post
      segregational cell killing-related systems appear to have evolved by in situ
      displacement of genes for toxins or antitoxins by functionally equivalent but
      evolutionarily unrelated genes. We predict that the novel post-segregational cell
      killing-related systems containing a PilT-N terminal domain toxin and the
      eukaryotic nonsense-mediated RNA decay system are likely to function via a common
      mechanism, in which the PilT-N terminal domain cleaves ribosome-associated
      transcripts. The core of the eukaryotic nonsense-mediated RNA decay system has
      probably evolved from a post-segregational cell killing-related system.

PMID- 14659019
TI  - Comparing cDNA and oligonucleotide array data: concordance of gene expression
      across platforms for the NCI-60 cancer cells.
AB  - Microarray gene-expression profiles are generally validated one gene at a time by
      real-time RT-PCR. We describe here a different approach based on simultaneous
      mutual validation of large numbers of genes using two different expression
      profiling platforms. The result described here for the NCI-60 cancer cell lines
      is a consensus set of genes that give similar profiles on spotted cDNA arrays and
      Affymetrix oligonucleotide chips. Global concordance is parameterized by a
      'correlation of correlations' coefficient.

PMID- 14659021
TI  - Lung cancer: search for a marker.

PMID- 14659020
TI  - Multiclass classification of microarray data with repeated measurements:
      application to cancer.
AB  - Prediction of the diagnostic category of a tissue sample from its gene-expression
      profile and selection of relevant genes for class prediction have important
      applications in cancer research. We have developed the uncorrelated shrunken
      centroid (USC) and error-weighted, uncorrelated shrunken centroid (EWUSC)
      algorithms that are applicable to microarray data with any number of classes. We
      show that removing highly correlated genes typically improves classification
      results using a small set of genes.

PMID- 14659023
TI  - Application of genomics and proteomics to developments of novel therapies for
      lung cancer.

PMID- 14659022
TI  - Highlights from: 2nd International Lung Cancer Congress Kauai, Hawaii, July 18
      21, 2001.

PMID- 14659024
TI  - Strategies to restore p53 function in patients with lung cancer.

PMID- 14659025
TI  - Malignant pleural mesothelioma: surgical roles and novel therapies.
AB  - Malignant pleural mesothelioma (MPM) is a uniformly fatal disease that has been
      recalcitrant to curative therapies. Median survivals of 8-18 months have, for the
      most part, led to a sense of frustration and nihilism in the medical and surgical
      community with regard to management of the disease, and the relatively small
      numbers of patients with mesothelioma have made it an orphan among other cancers
      with regard to research efforts and funding. This review will comment on the
      clinical presentation of the disease and therapeutic options that are available
      at this time. The role, timing, degree, and availability of cytoreductive surgery
      in the context of a multimodality approach for MPM will be highlighted, and
      various strategies that incorporate adjunctive therapies before, during, or after
      the operation will be discussed. Newer cytotoxic chemotherapies, either alone or
      in combination, are reviewed, with an emphasis on the increasing number of
      options with increased response rates that are becoming available for MPM
      patients. The results of protocols at selected centers that offer gene therapy,
      photodynamic therapy, hyperthermic chemotherapeutic perfusion, and intrapleural
      chemokines will be discussed, as well as newer preclinical approaches that base
      targeted therapies on novel molecular findings. In considering the newest
      approaches to the disease, one is encouraged to seek specialty consultation at
      centers that concentrate programmatic efforts on mesothelioma in order to design
      translational-based approaches on preclinical findings. By using such an
      approach, the patient and physician will find that there are considerably more
      options in the new century for mesothelioma.

PMID- 14659026
TI  - Second-line chemotherapy for small-cell lung cancer: a review.
AB  - Small-cell lung cancer (SCLC) is an aggressive malignancy, and only a minority of
      patients survive 2 years. Although this cancer is sensitive to both chemotherapy
      and radiotherapy, the majority of patients relapse, and second-line treatment is
      an option for many. Currently in the United States, the combination of
      cisplatin/etoposide is the standard first-line therapy in SCLC. At this time,
      topotecan is the only Food and Drug Administration-approved chemotherapeutic
      agent for second-line treatment of SCLC. In this paper, we review studies of
      second-line chemotherapy for SCLC.

PMID- 14659027
TI  - Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic
      radiotherapy in locally advanced non-small-cell lung cancer: an interim report.
AB  - The paclitaxel/carboplatin combination has demonstrated promising activity in
      metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an
      exploratory study of these agents with thoracic radiation (TRT) in locally
      advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%,
      weight loss <or= 5%, and primarily stage IIIB or bulky IIIA NSCLC. Induction
      chemotherapy (CT), 2 cycles of paclitaxel 175-225 mg/m2 over 3 hours and
      carboplatin (targeted area under the curve [AUC] of 7.5), was administered on
      days 1 and 22. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was
      given on days 2-15 and 23-36 to all patients; half were randomized to priming G
      CSF every day x 5 prior to day 1 of induction therapy. On day 43, TRT (60-63
      Gy/30-34 fx) was initiated. At dose level 1, only Fox Chase Cancer Center
      patients received carboplatin (initial target AUC 3.75) and paclitaxel (67.5
      mg/m2 over 3 hours) days 43 and 64. In the absence of dose-limiting toxicity,
      phase I dose escalation in 3-patient cohorts was scheduled to proceed to a
      maximum carboplatin AUC 7.5 and paclitaxel dose of 210 mg/m2. To date, 53
      patients have received induction therapy; 4 are too early to evaluate. The
      portion of the study evaluating G-CSF priming revealed no myeloprotective effect,
      likely due to a lack of myelosuppressive toxicity with the conventionally dosed
      cohort. Twenty-two patients have received concurrent TRT/CT. In sequential
      cohorts, the chemotherapy doses on days 43 and 64 have been escalated (to
      paclitaxel 175 mg/m2 and carboplatin AUC 5) with 1 episode each of grade 4
      granulocytopenia and grade 3 anemia. The occurrence of grade >or= 2 esophagitis
      has corresponded to length (> 16 cm) of esophagus in the radiation treatment
      field (Fisher's exact test, P = 0.006). The partial response rate to induction
      therapy was 40% and to the combined modality therapy was 60%. The median survival
      for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of
      7.8 months. In the subset of 22 patients treated on the phase I portion of the
      study, the median survival and DFS were 18.5 months and 13.5 months,
      respectively. Induction therapy with paclitaxel and carboplatin followed by
      concurrent chemoradiotherapy with the same agents is an active and well-tolerated
      treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus
      carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in
      combination with TRT.

PMID- 14659029
TI  - Expression of E-cadherin and lymph node metastasis in resected non-small-cell
      lung cancer.
AB  - This study was conducted to clarify the relationship between E-cadherin
      expression on tumor and lymph node metastasis as well as its prognostic roles in
      resected non-small-cell lung cancer. Two hundred forty-nine patients, who
      underwent surgical resection (stage I-IIIA), were examined. Paraffin-embedded
      sections of the primary tumors in all cases and of the metastatic lymph nodes in
      stage IIIA disease were stained with a monoclonal antibody against E-cadherin.
      Decreased expression of E-cadherin correlated with pathologic stage, tumor size,
      lymph node metastasis, and histological grade. The 5-year survival rate of E
      cadherin-negative patients with stage IIIA disease was significantly lower than
      that of E-cadherin-positive patients. Multivariate analysis in stage IIIA disease
      indicated that E-cadherin was an independent prognostic factor. In the patients
      with clinical N0 tumors, the frequency of pathological N2 tumors was
      significantly higher in cases where the primary tumor was recognized as E
      cadherin expression negative than in cases where the primary tumor was recognized
      as positive. Decreased E-cadherin expression showed correlation with presence of
      lymph node metastasis in resected non-small-cell lung cancer and with the
      prognosis of patients with stage IIIA disease.

PMID- 14659030
TI  - Three-dimensional conformal radiation therapy (3D-CRT) for early-stage non-small
      cell lung cancer.
AB  - The standard treatment for early-stage non-small-cell lung cancer is surgical
      resection. However, many patients are inoperable due to medical comorbidities.
      Thirty-two medically inoperable patients with early-stage non-small-cell lung
      cancer were treated with 3-dimensional conformal radiation therapy between
      January 1991 and December 2000. The median dose was 70.2 Gy, and the median
      follow-up time in survivors was 30 months. The 2-year actuarial local control,
      overall survival, and cancer-specific survival rates were 43%, 54%, and 57%,
      respectively. The 5-year actuarial local control, overall survival, and cancer
      specific survival rates were 43%, 33%, and 39%, respectively. This report
      suggests that local control is improved with high-dose conformal radiation
      therapy when compared to other institutions' retrospective experiences.

PMID- 14659031
TI  - The role of semaphorins in lung cancer.
AB  - The semaphorins are a family of secreted, transmembrane, and membrane-associated
      proteins initially identified as causing the repulsion of nerve growth cone
      guidance. However, subsequent experiments have demonstrated that they can induce
      retraction in non-neural cells and affect the development of non-neural organs.
      Two related secreted semaphorins, SEMA3F and SEMA3B, were isolated from a
      recurrent 3p21.3 homozygous deletion region in small-cell lung cancer (SCLC) cell
      lines. Moreover, a functionally related molecule, Roundabout/DUTT1, was
      identified as the target of a more proximal chromosome 3p deletion also involving
      SCLCs. Based on current data, it is likely that the loss of these semaphorins or
      Roundabout may affect cell migration, metastasis, and apoptosis. In addition,
      receptors for the secreted semaphorins, neuropilin-1 and neuropilin-2, have been
      shown to function as coreceptors for a subset of vascular endothelial growth
      factor (VEGF) isoforms and related growth factors. Since semaphorins and VEGF
      bind antagonistically to neuropilins, their loss is likely to facilitate
      angiogenesis. In lung cancer specimens, antibody staining against SEMA3F has been
      shown to correlate with stage and histologic subtypes with more aggressive tumors
      showing increased VEGF and decreased SEMA3F staining. This review is focused on a
      basic understanding of these pathways with an emphasis on their role in lung
      cancer.

PMID- 14659032
TI  - Non-small-cell lung cancer: dose escalation by target splitting with asymmetric
      collimation.
AB  - In order to increase conformation, the target volume is split into a cranial and
      a caudal part. Both volumes are planned and treated completely independent, using
      half-collimated fields to prevent over- or under-dosages in the junction plane.
      In comparison with conventional techniques, the irradiated volume of normal
      ipsilateral lung tissues at dose levels >or= 65 Gy, >or= 45 Gy, and >or= 20 Gy
      can be lowered to values of 37%, 49%, and 86%, respectively; other organs at
      risk, such as the heart and esophagus, can also be significantly spared. From
      December 1995 to December 1999, 54 non-small-cell lung cancer patients were
      treated with doses > 80 Gy (mean, 86.3 Gy; range 80.1-94.9 Gy, International
      Commission on Radiation Units and Measurements). Twenty-two patients were stage I
      or stage II, and 32 patients were stage III. Fifteen of the 32 stage III patients
      received chemotherapy before radiotherapy. Only 1 patient showed a transient
      grade 3 toxicity (pneumonitis), and at the time of this review, no grade 4/5
      toxicity has been observed.

PMID- 14659033
TI  - Current therapeutic approaches in lung cancer.

PMID- 14659034
TI  - The role of irinotecan combined with Cisplatin or Carboplatin in the treatment of
      advanced non-small-cell lung cancer.
AB  - More than one third of all non-small-cell lung cancer (NSCLC) patients present
      with advanced stage IV disease with metastases or with stage IIIB disease with a
      malignant pleural or pericardial effusion. The prognosis for these patients
      remains poor despite some improvement in survival produced by 2-drug chemotherapy
      combinations. With the best 2-drug combinations, the expected median survival is
      8-9 months and > 80% of patients die within 2 years of diagnosis. The overall
      response rate to the best combination is < 40% and the complete response rate is
      only 1%. Clearly, superior therapies are needed. The topoisomerase I inhibitors
      have been developed because the topoisomerase I enzyme plays a critical role in
      the DNA repair process. Irinotecan is a topoisomerase I inhibitor developed
      during the 1990s. It was initially approved in the United States for the
      treatment of colorectal cancer. In early trials, considerable activity was seen
      in both small-cell lung cancer and NSCLC. These observations led to combination
      studies with cisplatin. Cisplatin-based therapy had become a standard approach in
      both stage IV disease and in combination with chest radiotherapy in stage IIIB
      disease because metaanalyses of randomized trials showed that cisplatin-based
      therapy significantly improved survival. Randomized trials also showed that
      cisplatin-based therapy improved symptoms in the majority of patients and
      improved quality of life. In early combination studies, the irinotecan/cisplatin
      combination produced responses in an average of 40% of patients and produced
      median survival times that averaged about 10 months. In randomized trials
      comparing irinotecan/cisplatin to vindesine/cisplatin, the irinotecan/cisplatin
      combination was slightly better than irinotecan alone and vindesine/cisplatin.
      These encouraging results led to ongoing randomized trials comparing the 2-drug
      combination of irinotecan/cisplatin to other 2-drug combinations. Irinotecan has
      also been combined safely and effectively with carboplatin. The 2-drug
      combination of irinotecan/carboplatin produced results similar to those achieved
      with irinotecan/cisplatin. Irinotecan has also been incorporated into 3-drug
      combinations such as irinotecan/carboplatin/paclitaxel with encouraging results.
      A randomized trial comparing docetaxel/irinotecan to docetaxel/cisplatin showed
      similar results. Randomized trials comparing the 3-drug combination to a 2-drug
      combination are in progress. The irinotecan/cisplatin combination has
      considerable activity in the second-line setting. Randomized trials comparing
      this combination to docetaxel are needed. Irinotecan is an active agent in the
      first- and second- line therapy of NSCLC.

PMID- 14659035
TI  - Irinotecan/Taxane combinations in advanced non-small-cell lung cancer.
AB  - Although conventional therapies can produce median survival times of 8 months to
      1 year in non-small-cell lung cancer (NSCLC) patients, there is still much room
      for improvement. With the emergence of multiple new agents, there is an increased
      number of therapeutic options available. Irinotecan has demonstrated activity in
      small-cell lung cancer and promising overall response rates of up to 35% as a
      single agent in NSCLC. Irinotecan/paclitaxel is currently being tested in a phase
      II trial with encouraging preliminary results. The triplet
      irinotecan/carboplatin/paclitaxel has been tested in a phase II trial as well.
      This triplet combination has yielded an impressive median survival time of 12.5
      months and a 1-year survival rate of 50%, suggesting that this treatment regimen
      should be further explored. When used in combination with docetaxel, irinotecan
      has demonstrated comparable survival and response rates to the conventional
      cisplatin/docetaxel doublet but with lower toxicities. Ongoing and future trials
      will further clarify the role of irinotecan/taxane combinations in the treatment
      of NSCLC, both in treatment-naive patients and in the second-line setting.

PMID- 14659036
TI  - Irinotecan in non-small-cell lung cancer: status of ongoing trials.
AB  - Irinotecan possesses significant single-agent activity in non-small-cell lung
      cancer (NSCLC) and is active in combination with either cisplatin or carboplatin.
      Two phase III trials completed in Japan have suggested that the combination of
      irinotecan/cisplatin yields superior survival rates in stage IV NSCLC patients
      compared to vindesine/cisplatin. The principal toxicities of the
      irinotecan/cisplatin regimen are neutropenia and diarrhea. This regimen is
      currently being tested in Japan against regimens commonly used in the United
      States, such as cisplatin/gemcitabine, cisplatin/vinorelbine, and
      carboplatin/paclitaxel. These studies include evaluation of monthly as well as
      weekly schedules of cisplatin in combination with irinotecan as well as a triplet
      regimen of irinotecan/carboplatin/paclitaxel. Ongoing trials are evaluating these
      regimens as well as irinotecan/carboplatin and several nonplatinum-based
      irinotecan-containing doublets in both the first- and second-line treatment of
      advanced NSCLC. Several ongoing trials are attempting to integrate irinotecan
      with thoracic radiation therapy in stage III NSCLC. These trials are using
      irinotecan-containing regimens as induction and concurrent therapy with thoracic
      radiation therapy. Irinotecan is also being evaluated in the preoperative setting
      in early-stage resectable NSCLC. Many of these trials are also incorporating
      celecoxib, a potent inhibitor of the cyclooxygenase-2 pathway, in combination
      with irinotecan-containing regimens in both advanced as well as early-stage
      NSCLC. Future trials should focus on the integration of the new targeted agents
      in combination with irinotecan-containing regimens in all stages of NSCLC.

PMID- 14659037
TI  - Irinotecan Combined with Radiation Therapy for Patients with Stage III Non-Small
      Cell Lung Cancer: Current Trials.
AB  - The prognosis for non-small-cell lung cancer (NSCLC) patients remains poor, with
      a high percentage of patients presenting with advanced disease and metastases.
      Thus, the therapeutic goal is to provide optimal local control and to eradicate
      any metastases. The advent of novel therapies has provided new hope in the
      treatment of this disease. Irinotecan, a topoisomerase I inhibitor, is active in
      both chemotherapy-naive and previously treated NSCLC patients. In addition, its
      ability to act as a radiosensitizer makes it a promising candidate for use in
      combined modality therapy. Encouraging response rates have been achieved in
      multiple trials using irinotecan alone or in combination with cisplatin,
      carboplatin, docetaxel, and/or radiotherapy. Further phase II and III studies
      should clarify the benefit of combined modality therapy as well as the optimal
      way to integrate radiotherapy into irinotecan regimens.

PMID- 14659038
TI  - Therapy of advanced non-small-cell lung cancer with irinotecan and gemcitabine in
      combination.
AB  - Non-small-cell lung cancer is the leading cause of cancer-related deaths in the
      United States. Chemotherapy has been shown to improve survival and quality of
      life in patients with advanced disease when compared to best supportive care. Of
      the commonly used therapies, platinum in combination with gemcitabine, taxanes,
      and vinorelbine offers superior activity to single-agent platinum or older
      platinum combinations. In addition, single-agent gemcitabine or single-agent
      paclitaxel has resulted in lower survival compared to each in combination with
      carboplatin in 2 recently reported phase III trials. However, among themselves
      new doublets have shown no improvement in survival, and treatment has
      traditionally been chosen based on convenience and toxicity rather than efficacy.
      The combination of gemcitabine and irinotecan has demonstrated promising results
      in preclinical studies. In this review, the data available on the combination of
      gemcitabine and irinotecan in phase I and phase II trials are discussed.

PMID- 14659039
TI  - Irinotecan in small-cell lung cancer: current data and the status of ongoing
      trials.
AB  - Small-cell lung cancer (SCLC) is a particularly aggressive form of lung cancer
      and is associated with a poor prognosis, rapid tumor growth, and early
      metastasis. Currently, the cornerstone of treatment in SCLC consists of
      combination therapy, with platinum/etoposide being the regimen of choice.
      Unfortunately, even with these advances in treatment, the median survival for
      patients with limited-stage disease is 10-15 months and 7-11 months for patients
      with extensive-stage disease. New treatment mechanisms need to be explored in
      order to extend the survival of SCLC patients. One such new treatment is the
      topoisomerase I inhibitor, irinotecan. This drug represents a promising
      advancement in the treatment of SCLC.

PMID- 14659040
TI  - From regenerative medicine to human design: what are we really afraid of?

PMID- 14659041
TI  - Targeting Stat3 with G-quartet oligodeoxynucleotides in human cancer cells.
AB  - Stat3 is an oncogene that is activated in many human cancer cells. Genetic
      approaches that disrupt Stat3 activity result in inhibition of cancer cell growth
      and enhanced cell apoptosis supporting the development of novel drugs targeting
      Stat3 for cancer therapy. G-quartet oligodeoxynucleotides (ODNs) were
      demonstrated to be potent inhibitors of Stat3 DNA binding activity in vitro with
      the G-quartet ODN, T40214, having an IC(50) of 7 microM. Computer-simulated
      docking studies indicated that G-quartet ODNs mainly interacted with the SH2
      domain of Stat3 and were capable of inserting between the SH2 domains of Stat3
      dimers bound to DNA. We demonstrated that the G-rich ODN T40214, which forms a G
      quartet structure at intracellular but not extracellular K+ ion concentrations,
      is delivered efficiently into the cytoplasm and nucleus of cancer cells where it
      inhibited IL-6-stimulated Stat3 activation and suppressed Stat3-mediated
      upregulation of bcl-x and mcl-1 gene expression. Thus, G-quartet represents a new
      class of drug for targeting of Stat3 within cancer cells.

PMID- 14659043
TI  - Analysis of Indian population based on Y-STRs reveals existence of male gene flow
      across different language groups.
AB  - A study of three different Y-specific microsatellites (Y-STRs) in the populations
      from Uttar Pradesh (UP), Bihar (BI), Punjab (PUNJ), and Bengal (WB), speaking
      modern indic dialects with its roots in Indo-Aryan language, and from South of
      India (SI), speaking the South Indian languages with their root in Dravidian
      language, has shown that the predominant alleles observed represent the whole
      range of allelic variation reported in different population groups globally.
      These results indicate that the Indian population is most diverse. The similarity
      between the allelic variants between the populations studied by others in Africa
      and Asia and in this study between WB, PUNJ, UP, BI, and SI are of interest. It
      demonstrates that these population groups, housed in eight states of the country
      in different geographic locations, broadly correspond with Indo-Aryan and
      Dravidian language families. Further, our analyses based on haplotype frequency
      of different marker loci and gene diversity reveals that none of the population
      groups have remained isolated from others. High levels of haplotype diversity
      exist in all the clusters of population. Nonsignificant results based on Markov
      chain steps and Slatkin's linearized genetic distances indicate that there has
      been migration to and from in these population groups. However, some of the
      marginally significant interpopulation differences could be attributed to one or
      more of the castes with high diversity embedded within the population groups
      studied. Haplotype sharing between populations, F(ST) statistics, and
      phylogenetic analysis identifies genetic relatedness to be more between
      individuals belonging to two different states of India, WB and PUNJ, followed by
      UP and BI, whereas SI branched out separately.

PMID- 14659042
TI  - Folate biosynthesis pseudogenes, PsifolP and PsifolK, and an O-sialoglycoprotein
      endopeptidase gene homolog in the phytoplasma genome.
AB  - Phytoplasmas are wall-less phytopathogenic prokaryotes of small genome sizes that
      are obligate parasites of insect vectors and plant hosts. We have cloned a clover
      phyllody (CPh) phytoplasma DNA locus containing five potential coding sequences.
      Two were identified as pseudogenes (PsifolP and PsifolK) homologous to folP and
      folK genes, which encode dihydropteroate synthase (DHPS) and 6-hydroxymethyl-7,8
      dihydropterin pyrophosphokinase (HPPK), respectively, in other bacteria.
      Evolution of the phytoplasma presumably involved loss of functions through the
      formation of these and other pseudogenes during adaptation to obligate
      parasitism. The findings suggest that the phytoplasma lacks capacity for de novo
      folate biosynthesis and possesses a transport system for absorption of preformed
      folate from host cells. The PsifolP-PsifolK region was flanked by three open
      reading frames (ORFs) encoding a DegV family protein, a hypothetical protein with
      a P60-like lipoprotein domain homologous with the P60-like Mycoplasma hominis
      protein, and a glycoprotease (Gcp) protein that possibly functions as a host
      adaptation or virulence factor.

PMID- 14659044
TI  - Clinical aspects for the use of DNA image cytometry in detection of bladder
      cancer: a valuable tool?
AB  - The employment of DNA flow or image cytometry for oncological diagnostic
      procedures is favored because of its high correlation to tumor biological
      behavior. Prognostic statements and therapeutic strategies therefore are based on
      the high validity of DNA cytometric measurements. Using 151 bladder washings from
      patients suspected of bladder cancer for this study, we examined the clinical
      value of various common methods of DNA single cell (SCI) and stemline
      interpretations (SLI). Comparing the specificity and sensitivity of DNA image
      cytometry in detection of bladder tumors, we found 81 and 52%, respectively, for
      SCI of Boecking, 84 and 45% for SLI of Boecking, 61 and 58% for SLI of Fu, and 82
      and 40% for conventional stemline interpretation. To improve diagnostic and
      prognostic validity of DNA image cytometry, we designed our own method of
      interpretation. In consequence, we identified six single DNA parameters out of
      all recorded measurements that correlated most to histopathological grading (G1
      G3). Creating reference values at random and rating by points, we used a
      cytometric grading system for ranking. In detection of bladder cancer specificity
      and sensitivity ultimately arrived at almost 70% in application of our method.
      Thus, by this study, we were able to show that sensitivity of DNA examination can
      be increased by combining various DNA parameters. Apart from our own scheme, the
      discrepancy in interpretation of DNA image cytometry does not allow us to
      recommend this procedure as the only diagnostic in detection of bladder cancer.
      However, in regard to prognostic statements, particularly tumor biological
      behavior, DNA image cytometry appears to be useful.

PMID- 14659045
TI  - In vitro establishment of tumorigenic human B-lymphoblastoid cell lines
      transformed by Epstein-Barr virus.
AB  - We studied tumorigenic and phenotypic characteristics of pre- and postimmortal
      human B-lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus (EBV):
      preimmortal LCLs showed low telomerase activity and a normal diploid karyotype
      while postimmortal LCLs showed much higher telomerase activity and maintained a
      clonal aneuploidic state. Among five postimmortal LCLs tested, LCLs N0005 and
      N6803 formed colonies in agar medium and showed marked aneuploidy, and N6803 was
      transplantable into nude mice indicating that it had a complete malignant
      phenotype, but all preimmortal LCLs and the remaining three postimmortal LCLs
      lacked these characteristics. The products of tumor suppresser genes, p16(INK4A)
      and pRb, were downregulated in these two LCLs, and the p53 gene was mutated in
      N0005 LCL. We believe these results showed for the first time that some
      postimmortal EBV-transformed LCLs can become tumorigenic, contrary to previous
      reports, and that these LCLs provide an in vitro model of tumorigenesis induced
      by EBV.

PMID- 14659046
TI  - Sequence, genomic organization, and expression of the human ADP-ribosylation
      factor 6 (ARF6) gene: a class III ARF.
AB  - ADP-ribosylation factor 6 (ARF6) is a member of a family of ~20-kDa guanine
      nucleotide-binding proteins that has been implicated to function in membrane
      ruffling and cell motility, endocytosis, exocytosis, and membrane recycling.
      Sequence analysis of the human ARF6 gene indicates it spans 4004 bp, contains a
      single 98-bp intron within the 5'-untranslated region, and is localized to
      chromosome 14q21. Similar to the class II ARF transcripts, translation of the
      ARF6 mRNA initiates in the second exon. Primer extension assays indicate that the
      major transcription initiation site is located 591 bp 5' to the start of
      translation, yielding the largest 5'-untranslated region of the known human ARFs.
      The proximal 5'-flanking region of the human ARF6 gene lacks a TATA box and is
      highly GC rich. Consistent with this promoter structure, expression analysis of a
      blot containing 50 human RNAs hybridized with an ARF6-specific oligonucleotide
      probe revealed that the ARF6 gene is expressed in all tissues; although higher
      levels of expression were observed in heart, substantia nigra, and kidney. A
      comparison of the genomic organization of the ARF genes reveals that the ARF6
      gene (class III) structure is quite distinct from the class I (ARF1, ARF2, and
      ARF3) and class II (ARF4 and ARF5) ARF genes.

PMID- 14659047
TI  - Identification and characterization of the DdlB, FtsQ and FtsA genes upstream of
      FtsZ in Bartonella bacilliformis and Bartonella henselae.
AB  - Homologues of the cell division protein FtsZ were previously identified in
      Bartonella bacilliformis and Bartonella henselae. We report herein that ftsZ is
      located at the distal end of an operon that includes ddlB, ftsQ, and ftsA. These
      genes code for homologues of D-alanine D-alanine ligase, an enzyme involved in
      cell wall biosynthesis, and FtsQ, and FtsA, which are involved in cell division.
      The DdlB, FtsQ, and FtsA proteins from Bartonella species are most homologous to
      proteins in closely related species from the Order Rhizobiales, such as Brucella
      sp., Agrobacterium tumefaciens, and M. loti. The organization of the genes within
      the ddlB-ftsZ operon of B. bacilliformis and B. henselae (5'ddlB-ftsQ-ftsA-ftsZ
      3') is similar to that of Mesorhizobium loti and Escherichia coli. We report the
      localization of three promoter regions within the ddlB-ftsA sequence of B.
      bacilliformis that may enhance the transcription of ftsZ mRNA. A promoter region
      was also identified upstream of the ddlB gene.

PMID- 14659048
TI  - [Biologic significance of neurofilament protein expression in scar tissue].
AB  - OBJECTIVE: To investigate the situation of neurofilament protein (NFP) and
      epidermal growth factor receptor (EGFR) staining in scars and normal human skin,
      and attempt to explain the etiology of scarring formation. METHODS: The samples
      of scar were obtained from post-burn (11-26 months) patients undergoing plastic
      operation in our burn unit recently, and the samples of control came from skin
      donor site of the same patient correspondingly. Immunohistochemistry staining
      technique was employed to examine the protein expression in scars and skin. The
      expression of neurofilament protein (NFP-200) and EGFR in hyperplastic scars
      (n=12) and normal human (n=12) were investigated with light microscope. RESULTS:
      The expression of NFP-200 and EGFR in hyperplastic scars were much higher than
      that in normal human skin,and NFP-200 immuno-reaction nerve fibers were
      progressively stronger with scarring formation, then were gradually reduced with
      scarring maturation. The change of EGFR expression was similar to NFP-200
      expression. CONCLUSION: These studies are undertaken to elucidate the
      relationship between scars formation and nerve reinnervation in cutaneous cells.
      The activity of EGFR might be associated with the nerve reinnervation. The
      expression of EGFR influence on wound healing. Therefore, neuroregulation might
      play a role in the pathogenesis of scars.

PMID- 14659049
TI  - [Strengthen the study of emergency medical system on disaster and incident].

PMID- 14659050
TI  - [Measure on medical care and rescue for the first Chinese astronaut during manned
      space flight].
AB  - OBJECTIVE: To discuss the experience of medical care and rescue for the first
      Chinese astronaut during manned space flight. METHODS: Review the experiences of
      foreign nations in respect to accidental injuries of astronaut during manned
      space flight, the possible reasons were analyzed, and accordingly a reasonable
      and effective prophylactic measures and health care were formulated. RESULTS: An
      effective mobile intensive care unit (ICU) was established on desert or prairie
      where the capsule would land, so as to ensure the safety of the first Chinese
      astronaut, and to provide intensive care as well as successful emergency
      treatment in case of accidental injuries. CONCLUSION: Reasonable and effective
      prophylactic measures and health care appear to be an important aspect of the
      successful manned space flight.

PMID- 14659051
TI  - [Clinical significance of detection of serum hyaluronic acid concentration in
      severe burn patients].
AB  - OBJECTIVE: To study the relationship between the changes in serum hyaluronic acid
      (HA) concentrations and injury of hepatocytes in severe burn patients. METHODS:
      Radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) were used to
      detect HA and tumor necrosis factor-alpha(TNF-alpha) concentrations in serum, and
      biochemical indexes for hepatic function and renal function in burn patients that
      were divided into different groups: systemic inflammatory response
      syndrome(SIRS), multiple organ dysfunction syndrome(MODS). Multiple organ
      failure(MOF) and non-surviving patient groups. RESULTS: In two weeks after burns,
      the serum HA concentration attained a high level. With the increase of severity
      of disease, the values of the serum HA concentration were elevated progressively
      (P<0.001). At the onset of MOF till death, the serum HA content was rapidly
      decreased. Lineal correlation analysis indicated that the change in the serum HA
      concentration was closely correlated with SIRS, burn sepsis, MODS and death
      (P<0.01). It was positively correlated with TNF-alpha, aspartate aminotransferase
      (AST) and total bilirubin (P<0.05 or P<0.01), and negatively correlated with
      plasma albumin and albumin/globulin(both P<0.05). CONCLUSION: The increment in
      serum HA levels is relate with the impairment of the hepatic endothelial cells
      due to TNF-alpha etc. The HA content in serum can be used as a sensitive
      indicator for judging injury of liver, seriousness of the injury, and prognosis
      of the patient.

PMID- 14659053
TI  - [Primary research of the effect of intestinal ischemia/reperfusion injury on
      Leptin concentrations].
AB  - OBJECTIVE: To explore the effect of intestinal ischemia/reperfusion injury on
      Leptin concentrations in serum and adipose tissue, and to find out the role of
      Leptin in acute inflammatory responses. METHODS: An intestinal ischemia
      reperfusion injury model of rats was established, and used a highly-sensitive
      murine Leptin radioimmunoassay to check the change of Leptin concentrations in
      serum and adipose tissue. RESULTS: Serum Leptin level (10.82+/-0.83) microg/L
      significantly decreased after an injury of 60-minute ischemia and 30-minute
      reperfusion versus pre-experimental serum levels (16.46+/-3.21) microg/L; Leptin
      level in serum was higher than that in adipose tissue (4.466+/-2.63) mg/100g, and
      they both showed a similar changeable trend to increase step by step as
      reperfusion time extended (P=0.047). CONCLUSION: Leptin may be an inflammatory
      cytokine and may play a role in inflammatory responses such as intestinal
      ischemia/reperfusion.

PMID- 14659054
TI  - [Localization and role of dendritic cells in rat kidney with renal ischemia/
      reperfusion injury].
AB  - OBJECTIVE: To investigate the localization and the role of dendritic cells (DCs)
      in rat kidney with renal ischemia/reperfusion injury, and to explore the effect
      of anti-P-selectin Lectin-epidermal growth factor (EGF) domain monoclonal
      antibody (PsL-EGFmAb) on DCs. METHODS: (1)Rat model of renal ischemia/reperfusion
      was established and rats were divided into treated group with PsL-EGFmAb (n=20)
      and untreated group (n=20), which included four sub-groups respectively according
      to reperfusion time (1-hour,3-hour, 6-hour, 24-hour), sham group (n=5) severed as
      control. CD1a(+)CD80(+)DC was observed with microscopy images method and P
      selectin was analysed with immunohistochemistry. RESULTS: (1)In renal tissues of
      untreated group, CD1a(+)CD80(+)DC was found in renal tubules, interstitium and
      vessels, especially in renal tubules and interstitium, but DCs were hardly
      observed in sham group (P<0.001). The number of CD1a(+)CD80(+)DC in 24-hour group
      was greater than those in other groups (P<0.01). The number of DCs was positively
      associated with blood urea nitrogen and serum creatinine (both P<0.05). (2)P
      selectin content was increased significantly after ischemia/reperfusion 1 hour.
      (3)The contents of DC and P-selectin were decreased after treated (P<0.05 and
      P<0.01) in rat renal tissues. CONCLUSION: DCs play an important role in immune
      pathogenesis after renal ischemia/reperfusion injury, which is related to renal
      immigration of DCs mediated by P-selectin. PsL-EGFmAb may inhibit local DCs
      immigration and accumulation in kidney.

PMID- 14659055
TI  - [Application of non-invasive hemodynamic monitoring on high-risk surgical
      patients in the early stages after emergency admission].
AB  - OBJECTIVE: Pulmonary artery (PA) catheterization monitoring (Swan-Ganz) is
      usually not available to critically high-risk surgical patients before admission
      to ICU, where action to correct values derived from such monitoring may be too
      late. To explored the effect of non-invasive monitoring systems that allow
      hemodynamic monitoring during the early stages after trauma. METHODS: The early
      temporal hemodynamic patterns after high-risk trauma with non-invasive monitoring
      systems were evaluated, and compared these to invasive PA monitoring. The study
      included 156 patients monitored shortly after admission to the emergency
      department. RESULTS: The non-invasive impedance cardiac output estimations under
      extenuating emergency conditions were similar to those of the thermodilution
      method: r=0.69, r(2)=0.87, P<0.001; bias and precision were (0.62+/-0.38)L. min(
      1).m(-2). In ICU, these values improved further to: r=0.84, r(2)=0.93, P<0.001;
      bias and precision were (0.36+/-0.15) L.min(-1).m(-2). Monitoring revealed
      episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low
      transcutaneous oxygen and high transcutaneous carbon dioxide tension, and low
      oxygen consumption during initial resuscitation. Low flow and poor tissue
      perfusion were more pronounced in non-survivors by both METHODS. CONCLUSION:
      Multicomponent non-invasive monitoring systems offer continuous on-line, real
      time display of hemodynamic data, they allow early recognition of circulatory
      dysfunction. Such systems provide information similar to that provided by the
      invasive thermodilution method, and are more effective and safer.

PMID- 14659057
TI  - [Escharectomy during burn shock on Th1/Th2 polarization of helper T lymphocytes
      in rats after thermal injury].
AB  - OBJECTIVE: To determine the type-1/type-2 cytokine response of helper T
      lymphocytes after thermal injury, and to investigate the effects of escharectomy
      during burn shock stage on the polarization of Th cells. METHODS: One hundred and
      sixty male Wistar rats were randomized into four groups. In group A, animals were
      subjected to a 30 percent full-thickness thermal injury without escharectomy. In
      groups B, C and D, escharectomy and skin allograft were done at 8, 24, and 96
      hours postburn, respectively. At 4, 12, 24, 48, 96, 120 and 168 hours postburn,
      animals were killed and bloods samples as well as spleens were harvested. Enzyme
      linked immunoadsorbent assay (ELISA) was applied to determine interferon
      gamma(IFN-gamma) and interleukin-4(IL-4) levels in blood and spleen tissues.
      RESULTS: Levels of IFN-gamma and IL-4 rapidly and significantly were increased
      after scald injury. IFN-gamma levels began to rise within 4 hours postburn,
      peaking at 24 hours later. IL-4 showed a persistent elevation up to 168 hours
      postburn, thereby leading to a dominant tendency of Th2 cytokine response on
      postburn day 7. In group A, all above parameters revealed most obvious changes
      compared with controls, then ranked in group D, B and C. CONCLUSION: Escharectomy
      during burn shock stage is helpful to prevent the shift to Th2 cell response
      after severe thermal injury.

PMID- 14659059
TI  - [Fluid resuscitation in traumatic shock].
AB  - OBJECTIVE: To investigate fluid resuscitation affecting the result of treatment
      of patients with traumatic shock. METHODS: Two hundred and fifty-six cases of
      patients with traumatic shock treated in our hospital between January 1989 and
      December 2002 were analysed retrospectively, and the volume-effect relationship
      between fluid resuscitation during the first hour and future of traumatic shock
      was summarised. RESULTS: The successful rate of resuscitation was 73.05 percent
      (187 cases), and traumatic mortality was 26.95 percent (69 cases). After 1-hour
      trauma, the survival rate was 52.27 percent in patients with 1 liter of
      resuscitation fluid, 75.90 percent in patients with 15-20 liter of resuscitation
      fluid, and 78.29 percent of more than 20 liter resuscitation fluid, 86.79 percent
      in mild shock, 80.34 percent in middle shock and 54.65 percent in severe shock.
      CONCLUSION: Severe trauma and shock, hypotension and incorrect resuscitation
      manipulation are the main factors affecting the result of resuscitation and
      treatment of traumatic shock. It is important to early and correctly expand,
      especially at the first hour. The aim of resuscitation of traumatic shock is to
      maintain the hemodynamics and correct O2 defect.

PMID- 14659060
TI  - [Comparison of serum leptin clearance with different blood purification].
AB  - OBJECTIVE: To compare the serum Leptin clearance efficiency with different blood
      purification treatment. METHODS: Thirty-one chronic end-stage renal failure
      hemodialysis (HD) patients (16 men, 15 women, mean age (54.0+/-11.0) years) were
      enrolled into the study. All the patients were treated with routine hemodialysis,
      the serum Leptin levels were examined before and after HD. Then they were divided
      into two groups, one was to be treated with hemodiafiltration (12 patients), and
      the other was to be treated with blood adsorption (8 patients). The same serum
      Leptin levels were examined before and after treatment. Serum Leptin
      concentration was detected by radioimmunoassay (RIA). RESULTS: The concentration
      of serum Leptin was not significantly decreased after routine hemodialysis in HD
      patients ((11.820+/-5.507) microg/L vs. (12.255+/-5.172) microg/L, P>0.05).
      Leptin concentrations after hemodiafiltration and blood adsorption therapy were
      decreased to the levels of (29.07+/-8.56) percent and (40.29+/-8.33) percent
      respectively, and their curative effect was significantly different (P=0.001).
      CONCLUSION: Routine hemodialysis can influence serum Leptin levels in HD
      patients. Hemodiafiltration and blood adsorption therapy can lower serum Leptin
      levels. Blood adsorption therapy is better than hemodiafiltration in the
      clearance of serum Leptin.

PMID- 14659061
TI  - [Development and its clinical application of an acid-base balance computer
      software].
AB  - OBJECTIVE: To develop acid-base balance computer software for estimating acid
      base disturbance rapidly and accurately. METHODS: The data module was set up,
      based on Henderson-Hasselbalch (H-H) and compensation formula, and the program
      was written with Delphi 5.0. RESULTS: The right RESULTS was 100.0 percent in 118
      cases of acid-base disturbance patients by the software, while those with the
      right RESULTS was 89.8 percent by hands (P<0.05). In 20 cases pure acid-base
      disturbance, 70 cases double acid-base disturbance and 28 cases with triple acid
      base disturbance, it took only (9.0+/-0.6) seconds, (8.9+/-1.3) seconds and
      (9.1+/-1.6)seconds respectively, with software, while which were much less than
      those by hands ((20.4+/-16.8) seconds, (92.4+/-45.3) seconds and (128.6+/-66.4)
      seconds, respectively, P<0.001). CONCLUSION: This software has a terse interface,
      by which the acid-base disturbance was concluded exactly and quickly.

PMID- 14659062
TI  - [Carbachol alleviates inflammation in gut tissue during ischemia/reperfusion in
      rats].
AB  - OBJECTIVE: To investigate the effects of carbachol on local inflammation in gut
      tissue during ischemia/reperfusion (I/R). METHODS: A jejunal sac was formed in
      Wistar rats. The superior mesenteric artery was occluded (SMAO) for 60 minutes
      followed by reperfusion for another 60 minutes. Animals were divided into three
      groups, pretreatment group (carbachol was injected into the jejunal sac 30
      minutes after SMAO, 0.1 mg/kg), treatment group (carbachol was injected in same
      dosage into the jejunal sac 30 minutes after reperfusion), and controls (saline
      injection). The contents of tumor necrosis factor-alpha(TNF-alpha) and activity
      of myeloperoxidase (MPO) in gut tissue were determined at 1 hours, 2.5 hours and
      6 hours after SMAO. RESULTS: The contents of TNF-alpha and activity of MPO were
      significantly decreased in pretreatment and treatment groups compared with
      control group at 2.5 hours after SMAO (both P<0.05). There were no differences in
      both contents between pretreatment group and treatment group at any specified
      time. It was also found that there were less inflammatory pathological changes in
      the gut tissues in the two treated groups than that of control. CONCLUSION: The
      RESULTS suggest that carbachol could alleviate gut inflammatory response during
      gut ischemia/reperfusion injury by inhibiting proinflammatory cytokine release.

PMID- 14659063
TI  - [Study on the relationship between changes of adrenomedulin in plasma and
      vascular resistance during traumatic shock in rats].
AB  - OBJECTIVE: To observe the changes of adrenomedulin in plasma and vascular
      resistance during traumatic shock in rats. METHODS: The concentration of
      adrenomedulin in plasma of rats after traumatic shock was detected by radio
      immunization. Mean arterial pressure, total peripheral vascular resistance (TPVR)
      and cardiac index (CI) were estimated by electrical conductance method. RESULTS:
      The concentration of adrenomedulin in plasma of traumatic shock without
      resuscitation group (68.34+/-3.71)ng/L and traumatic shock with resuscitation
      group (146.27+/-9.83)ng/L were higher than that of control group(32.63+/
      7.55)ng/L (P<0.01 and P<0.05). TPVR of traumatic shock with resuscitation group
      (10.57+/-0.35) kPa.s.L-1 was lower than that of traumatic shock without
      resuscitation group (16.75+/-0.23) kPa.s.L-1(P<0.01) and its CI (215.59+/-1.29)
      ml.min-1.kg-1 was higher than that of traumatic shock without resuscitation group
      (143.11+/-0.86) ml.min-1.kg-1 (P<0.01). CONCLUSION: Adrenomedulin is closely
      correlated with changes of vascular resistance and plays an important role during
      pathophysiological processes in rats after traumatic shock.

PMID- 14659064
TI  - [Role of activation of renin angiotensin system in cyclosporine A nephropathy].
AB  - OBJECTIVE: To investigate the role of renin angiotensin system (RAS) activation
      in cyclosporine A nephropathy. METHODS: Rats were fed with low salt diet. After
      seven days, they were randomly divided into four groups: vehicle (n=7), CsA
      treated (n=7), CsA+verapamil (n=7), CsA+enalapril (n=7). All rats except vehicle
      received a daily subcutaneous injection of CsA (15 mg/kg) for four weeks. Plasma
      and renal tissue angiotensin II (Ang II) levels were measured by
      radioimmunoassay. The expression of angiotensin II type 1 receptor (AT1R) was
      examined by Northern blot. RESULTS: Plasma and renal tissue angiotensin II levels
      were significantly elevated in CsA treated rats when compared to that in vehicle
      rats ((190+/-36)ng/L vs. (492+/-92)ng/L, (29.8+/-6.0)ng/g vs. (8.7+/-1.7) ng/g,
      P<0.001). Enalapril reduced angiotensin II levels significantly (both P<0.05).
      The expression of AT1R mRNA was down-regulated by CsA, this down-regulation was
      reversed by enalapril. CsA treated animals showed marked tubulointerstitial
      fibrosis, enalapril lessened the tubulointerstitial fibrosis significantly
      (P<0.05). Verapamil did not improve tubulointerstitial fibrosis significantly
      (P>0.05). CONCLUSION: RAS activation plays an important part in CsA nephropathy.
      Blockade of RAS may retard the progression of tubulointerstitial fibrosis caused
      by CsA.

PMID- 14659065
TI  - [Value and economic analysis of emergency endoscopy in the diagnosis and
      treatment of massive upper gastrointestinal hemorrhage].
AB  - OBJECTIVE: To study the application value of emergency endoscopy in the diagnosis
      and treatment of massive upper gastrointestinal hemorrhage, and to evaluated by
      the economic analysis whether the emergency endoscopy was safe and effective,or
      shorten the hospitalization days and reduced the medical costs. METHODS: Ninety
      one patients with massive upper gastrointestinal hemorrhage were randomly divided
      into emergency endoscopy group (group A) and non-emergency endoscopy group (group
      B). The patients in group A underwent endoscopy as soon as the blood pressures
      were normal and the patients of group B underwent endoscopy at 24-48 hours after
      hospitalization. They would be treated depending on the conditions by endoscopy.
      Then the correct diagnosis rates, rebleeding rates, complication rates, mean
      hospitalization days, the endoscopy costs, the blood transfusion costs, the drugs
      costs and the total hospitalization costs of two groups were evaluated and the
      cost-effect ratio (C/E) was calculated. RESULTS: The correct diagnosis rates and
      the endoscopy costs of group A were higher than the group B (100.0 percent
      vs.90.2 percent, P<0.05; (714.78+/-263.54) yuan vs. (383.57+/-251.72) yuan,
      P<0.01), and the rebleeding rates, the mean hospitalizations days, the blood
      transfusion costs and the drugs costs and the total hospitalization costs were
      all lower compared to the group B (6.1 percent vs. 26.8 percent, P<0.05; (5.42+/
      1.70) days vs. (8.51+/-2.30) days, P<0.01; (791.80+/-258.35) yuan vs. (1270.29+/
      569.21) yuan, P<0.01; (945.22+/-125.82) yuan vs. (1223.81+/-254.44) yuan, P<0.01;
      (2785.76+/-353.26) yuan vs. (3 527.76+/-555.62)yuan, P<0.01. The C/E of group A
      was lower than the group B (2785.76 yuan per patient vs. 3527.76 yuan per
      patient, P<0.01). CONCLUSION: Emergency endoscopy is not only safe and effective
      but also economical in the diagnosis and treatment of massive upper
      gastrointestinal hemorrhage.

PMID- 14659066
TI  - [Dynamic change of vascular active materials and inflammatory mediums after acute
      organophosphate poisoning and its clinical significance].

PMID- 14659068
TI  - On-off regulation of 3' exonuclease excision to DNA polymerization by Exo+
      polymerase.
AB  - The role of 3' exonuclease excision in DNA polymerization was evaluated in primer
      extensions using 3' allele-specific primers that had exonuclease-digestible and
      exonuclease-resistant 3' termini. With exonuclease-digestible unmodified 3'
      mismatched primers, the exo+ polymerase yielded template-dependent products.
      Using exonuclease-resistant 3' mismatched primers, no primer-extended product
      resulted from exo+ polymerase. As a control, polymerase without proofreading
      activity yielded primer-dependent products from 3' mismatched primers. These data
      indicated that a successful removal of the mismatch is required for DNA
      polymerization from the 3' mismatched primers by exo+ polymerase. In addition to
      the well-known proofreading from this mismatch removal, the premature termination
      in DNA polymerization, due to the failure of the efficient removal of the
      mismatched nucleotides, worked as an off-switch in maintaining the high fidelity
      in DNA replication from exo+ polymerase.

PMID- 14659069
TI  - On/off switch mediated by Exo+ polymerases: experimental analysis for its
      physiological and technological implications.
AB  - The potential physiological role and technological application of the premature
      termination of DNA polymerization through the off-switch of exo+ polymerases were
      studied using 3' phosphorothioate-modified or unmodified primers with single base
      mismatch distal to the 3' terminus. With exonuclease-digestible unmodified
      primers, a gradient premature termination of DNA polymerization was observed when
      amplified with exo+ polymerases. With 3' allele specific phosphorothioate
      modified primers, an efficient off-switch effect occurred in the discrimination
      of a single nucleotide polymorphism when directly using genomic DNA. Clearly, the
      off-switch of exo+ polymerases is useful in biomedical research.

PMID- 14659070
TI  - Transforming growth factor-beta3 gene SfaN1 polymorphism in Korean nonsyndromic
      cleft lip and palate patients.
AB  - The nonsyndromic cleft lip and palate (NSCL/P) is a congenital deformity of
      multifactorial origin with a relatively high incidence in the oriental
      population. Various etiologic candidate genes have been reported with conflicting
      results, according to race and analysis methods. Recently, the ablation of the
      TGF-beta3 gene function induced cleft palates in experimental animals. Also,
      polymorphisms in the TGF-beta3 gene have been studied in different races;
      however, they have not been studied in Koreans. A novel A --> G single nucleotide
      polymorphism (defined by the endonuclease SfaN1) was identified in intron 5 of
      TGF-beta3 (IVS5+104 A > G). It resulted in different genotypes, AA, AG, and GG.
      The objective of this study was to investigate the relationship between the SfaN1
      polymorphism in TGF-beta3 and the risk of NSCL/P in the Korean population. The
      population of this study consisted of 28 NSCL/P patients and 41 healthy controls.
      The distribution of the SfaN1 genotypes was different between the cases and
      controls. The frequency of the G allele was significantly associated with the
      increased risk of NSCL/P [odds ratio (OR) = 15.92, 95% confidence interval (CI) =
      6.3-41.0]. The risk for the disease increased as the G allele numbers increased
      (GA genotype: OR = 2.11, 95% CI = 0.38-11.68; GG genotype: OR = 110.2, 95% CI =
      10.67 - 2783.29) in NSCL/P. A stratified study in patients revealed that the
      SfaN1 site IVS5+104A > G substitution was strongly associated with an increased
      risk of NSCL/P in males (p < 0.001), but not in females. In conclusion, the
      polymorphism of the SfaN1 site in TGF-beta3 was significantly different between
      the NSCL/P patients and the control. This may be a good screening marker for
      NSCL/P patients among Koreans.

PMID- 14659071
TI  - Identification of the most accessible sites to ribozymes on the hepatitis C virus
      internal ribosome entry site.
AB  - The hepatitis C virus (HCV) is a major causative agent of chronic hepatitis and
      hepatocellular carcinoma. The development of alternative antiviral therapies is
      warranted because current treatments for the HCV infection affect only a limited
      number of patients and lead to significant toxicities. The HCV genome is
      exclusively present in the RNA form; therefore, ribozyme strategies to target
      certain HCV sequences have been proposed as anti-HCV treatments. In this study,
      we determined which regions of the internal ribosome entry site (IRES) of HCV are
      accessible to ribozymes by employing an RNA mapping strategy that is based on a
      trans-splicing ribozyme library. We then discovered that the loop regions of the
      domain IIIb of HCV IRES appeared to be particularly accessible. Moreover, to
      verify if the target sites that were predicted to be accessible are truly the
      most accessible, we assessed the ribozyme activities by comparing not only the
      trans-splicing activities in vitro but also the trans-cleavage activities in
      cells of several ribozymes that targeted different sites. The ribozyme that could
      target the most accessible site identified by mapping studies was then the most
      active with high fidelity in cells as well as in vitro. These results demonstrate
      that the RNA mapping strategy represents an effective method to determine the
      accessible regions of target RNAs and have important implications for the
      development of various antiviral therapies which are based on RNA such as
      ribozyme, antisense, or siRNA.

PMID- 14659072
TI  - Molecular gene cloning, expression, and characterization of bovine brain
      glutamate dehydrogenase.
AB  - A cDNA of bovine brain glutamate dehydrogenase (GDH) was isolated from a cDNA
      library by recombinant PCR. The isolated cDNA has an open-reading frame of 1677
      nucleotides, which codes for 559 amino acids. The expression of the recombinant
      bovine brain GDH enzyme was achieved in E. coli. BL21 (DE3) by using the pET-15b
      expression vector containing a T7 promoter. The recombinant GDH protein was also
      purified and characterized. The amino acid sequence was found 90% homologous to
      the human GDH. The molecular mass of the expressed GDH enzyme was estimated as 50
      kDa by SDS-PAGE and Western blot using monoclonal antibodies against bovine brain
      GDH. The kinetic parameters of the expressed recombinant GDH enzymes were quite
      similar to those of the purified bovine brain GDH. The Km and Vmax values for
      NAD+ were 0.1 mM and 1.08 micromol/min/mg, respectively. The catalytic activities
      of the recombinant GDH enzymes were inhibited by ATP in a concentration-dependent
      manner over the range of 10 - 100 microM, whereas, ADP increased the enzyme
      activity up to 2.3-fold. These results indicate that the recombinant-expressed
      bovine brain GDH that is produced has biochemical properties that are very
      similar to those of the purified GDH enzyme.

PMID- 14659073
TI  - NMR studies on turn mimetic analogs derived from melanocyte-stimulating hormones.
AB  - Oligomers with alpha-aminooxy acids are reported to form very stable turn and
      helix structures, and they are supposed to be useful peptidomimetics for drug
      design. A recent report suggested that homochiral oxa-peptides form a strong
      eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid
      residues in a CDCl3 solution. In order to design an alpha-MSH analog with a
      stable turn conformation, we synthesized four tetramers and one pentamer, based
      on alpha-MSH sequence, and determined the solution structures of the molecules by
      two-dimensional NMR spectroscopy and simulated annealing calculations. The
      solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL)
      in DMSO-d6 contain a stable 7-membered-ring structure that is similar to a gamma
      turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball
      type rigid structure that is induced by strong hydrogen bonds between adjacent
      amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily
      prepared from natural or unnatural amino acids, can be employed to prepare
      peptidomimetic analogues with well-defined turn structures for pharmaceutical
      interest.

PMID- 14659074
TI  - Determining a detectable threshold of signal intensity in cDNA microarray based
      on accumulated distribution.
AB  - In microarray data mining, one of the key problems is how to handle weak signals.
      Based on a bent piecewise linear accumulated distribution generally found in the
      microarray data, a new detectable threshold finding method is proposed to filter
      genes with unreliable information in this paper. More reliable and reproducible
      data is produced for the subsequent data mining.

PMID- 14659075
TI  - Endotoxins of enteric pathogens modulate the functions of human neutrophils and
      lymphocytes.
AB  - The locomotor responses of human peripheral blood neutrophils and lymphocytes
      were measured by the change from spherical to polarized shapes in the presence of
      endotoxins (lipopolysaccharide, LPS) of enteric pathogens: S. dysenteriae type 1,
      V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae. We reported earlier
      that these endotoxins are chemotactic factors for the neutrophils since they
      stimulated cell polarization within a few minutes of incubation. Endotoxins had
      an inhibitory effect upon neutrophil phagocytosis of opsonized yeast and the
      cells engulfed fewer yeasts. Interestingly, endotoxins increased neutrophil
      adhesion to clean glass surfaces, but stimulated the cells to exhibit increased
      random locomotion (chemokinesis) through cellulose nitrate filters and show an
      enhanced ability to reduce nitroblue tetrazolium (NBT) dye. Unlike neutrophils,
      lymphocytes direct from blood do not show polarized morphology towards
      chemotactic factors but the cells acquire locomotor capacity during 24-72 h
      culture with mitogens such as phytohemagglutinin (PHA), phorbol myristate acetate
      or concanavalin A. Stimulation of blood lymphocytes with endotoxins did not
      induce cell polarization in short-term but long-term culture resulted in an
      increase in the proportion of polarized cells that acquired locomotor
      morphologies. The majority of these cells were identified as esterase negative B
      lymphocytes that migrated through filters. Despite the optimum time of incubation
      for each of these cell types being different, we found that lymphocytes respond
      to much lower concentrations of endotoxins than the neutrophils. These findings
      suggest that endotoxins of enteric pathogens modulate the functions of human
      blood neutrophils and lymphocytes.

PMID- 14659076
TI  - Isolation and characterization of major royal jelly cDNAs and proteins of the
      honey bee (Apis cerana).
AB  - An expressed sequence tag (EST) library was established from the hypopharyngeal
      glands of Apis cerana. Sixty-six recombinant clones, possessing inserts > 500 bp,
      were randomly selected and unidirectional sequenced. Forty-two of these (63.6%)
      were identified as homologues of Major Royal Jelly Proteins families 1, 2, 3, and
      4 of A. mellifera (AmMRJP) for which MRJP1 was the most abundant family. The open
      reading frame of the MRJP1 homologue (AcMRJP1) was 1299 nucleotides that encoded
      433 deduced amino acids with three predicted N-linked glycosylation sites. The
      AcMRJP1 sequence showed 93% and 90% homologies with nucleotide and deduced amino
      acid sequences of AmMRJP1, respectively. Two complete transcripts of apisimin,
      and one and two partial transcripts of alpha-glucosidase and glucose oxidase,
      were also isolated. In addition, the royal jelly proteins of A. cerana were
      purified and characterized using Q-Sepharose and Sephadex G-200 column
      chromatography. The native forms of protein peaks A1, A2, B1, and C1 were 115,
      55, 50, and 300 kDa, respectively. SDS-PAGE analysis indicated that A1 and C1
      were dimeric and oligomeric forms of the 80 kDa and 50 kDa subunits,
      respectively. The ratio of the total protein quantities of A1 : A2 : B1 : C1 were
      2.52 : 4.72 : 1 : 12.21. Further characterization of each protein, using N
      terminal and internal peptide sequencing, revealed that the respective proteins
      were homologues of MRJP3, MRJP2, MRJP1, and MRJP1 of A. mellifera.

PMID- 14659077
TI  - Isolation and localization of new germination-related sequences from wheat
      embryos.
AB  - Subtractive library hybridization was used to isolate the cDNA clones that
      corresponded to the transcripts that were specifically up-regulated during wheat
      embryo germination. The clones with numbers 5, 6, 7, 8, 24, and 26 appeared to be
      more abundant in germinating wheat embryos. Among the isolated clones, we
      identified four new members of the wheat "germin" gene family. We also identified
      two novel sequences which exhibited distinct germination up-regulation, and
      displayed characteristic spatial patterns of expression. One of these,
      represented by clone pSB10, was principally expressed in the root tissue of
      germinating embryos. The second was represented by the pSB7 clone and was
      expressed in both the root and shoot primordia of the embryonic axis, as well as
      within the coleoptile.

PMID- 14659078
TI  - Cloning and characterization of the promoters of temperate mycobacteriophage L1.
AB  - Four putative promoters of the temperate mycobacteriophage L1 were cloned by
      detecting the beta-galactosidase reporter expression in E. coli transformants
      that carried L1 specific operon-fusion library. All of the four L1 promoters were
      also found to express differentially in the homologous environment of
      mycobacteria. Of the four promoters, two were suggested to be the putative early
      promoters of L1 since they express within 0 to 10 min of the initiation of the
      lytic growth of L1. One of the putative early promoters showed a relatively
      better and almost identical activity in both E. coli and M. smegmatis. By a
      sequence analysis, we suggest that the L1 insert that contained the stronger
      early promoter possibly carries two convergent E. coli sigma70-like L1 promoters,
      which are separated from each other by about 300 nucleotides. One of them is the
      early promoter of L1 as it showed a 100% similarity with the early Pleft promoter
      of the homoimmune phage L5. The second promoter, designated P4, was suggested for
      its appreciable level of reporter activity in the absence of the -10 element of
      the Pleft equivalent of L1. By analyzing most of the best characterized
      mycobacteriophages-specific promoters, including the L1 promoter P4, we suggest
      that both the -10 and -35 hexamers of the mycobacteriophage promoters are highly
      conserved and almost similar to the consensus -10 and -35 hexamers of the E. coli
      sigma70 promoters.

PMID- 14659079
TI  - Nomega-nitro-L-arginine methylester ameliorates myocardial toxicity induced by
      doxorubicin.
AB  - The effects of Nomega-nitro-L-arginine methylester (L-NAME) and L-arginine on
      cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single
      dose of Dox 15 mg/kg i.p. induced cardiotoxicity, manifested biochemically by a
      significant elevation of serum creatine phosphokinase (CPK) activity [EC
      2.7.3.2]. Moreover, cardiotoxicity was further confirmed by a significant
      increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac
      tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water
      5 days before and 3 days after the Dox injection significantly ameliorated the
      cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity
      and lipid peroxides in the cardiac tissue homogenates. On the other hand, the
      administration of L-arginine 70 mg/kg/d p.o. did not protect the cardiac tissues
      against the toxicity that was induced by the Dox treatment. The findings of this
      study suggest that L-NAME can attenuate the cardiac dysfunction that is produced
      by the Dox treatment via the mechanism(s), which may involve the inhibition of
      the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy
      for cardiotoxicity that is induced by Dox and can then be used to improve the
      therapeutic index of Dox.

PMID- 14659080
TI  - Differential responses of rice acid phosphatase activities and isoforms to
      phosphorus deprivation.
AB  - Acid phosphatases (APases) play a role in the release of phosphate in organic
      complexes in soil. We investigated tissue- and isoform-specific responses of
      APases to phosphorus (P) deficiency in three rice genotypes; Dasan-byeo, Sobi
      byeo, and Palawan. The levels of shoot APase activity per protein were similar in
      the three genotypes. They significantly decreased with P deprivation that was
      longer than seven days. Root APase activity per protein was two- to three-fold
      higher in Dasan than in Sobi and Palawan. In all genotypes the APase activity
      increased in P-deficient plants, but the increase was higher in Sobi and Palawan.
      After 21 days of P deprivation, secreted APase activity increased more than eight
      fold in Dasan and two-fold in Sobi and Palawan. Isoform profiles of shoot and
      root APases were most diverse in Dasan. The activities of the major isoforms in P
      deficient shoots decreased in all three genotypes. Depending on the genotypes,
      further increases in constitutive isoforms and new induction of one to four
      isoforms occurred in P-deficient roots. The results indicate that tissue and
      genotype differences in the response of APase to P deficiency are primarily
      facilitated by the different responses of the isoforms.

PMID- 14659081
TI  - Resistance function of rice lipid transfer protein LTP110.
AB  - Plant lipid transfer proteins (LTPs) are a class of proteins whose functions are
      still unknown. Some are proposed to have antimicrobial activities. To understand
      whether LTP110, a rice LTP that we previously identified from rice leaves, plays
      a role in the protection function against some serious rice pathogens, we
      investigated the antifungal and antibacterial properties of LTP110. A cDNA
      sequence, encoding the mature peptide of LTP110, was cloned into the Impact-CN
      prokaryotic expression system. The purified protein was used for an in vitro
      inhibition test against rice pathogens, Pyricularia oryzae and Xanthomonas
      oryzae. The results showed that LTP110 inhibited the germination of Pyricularia
      oryzae spores, and its inhibitory activity decreased in the presence of a
      divalent cation. This suggests that the antifungal activity is affected by ions
      in the media; LTP110 only slightly inhibited the growth of Xanthomonas oryzae.
      However, the addition of LTP110 to cultured Chinese hamster ovarian cells did not
      retard growth, suggesting that the toxicity of LTP110 is only restricted to some
      cell types. Its antimicrobial activity is potentially due to interactions between
      LTP and microbe-specific structures.

PMID- 14659082
TI  - Growth of Escherichia coli in iron-enriched medium increases HPI catalase
      activity.
AB  - Escherichia coli has two catalases, HPI and HPII. HPI is induced during
      logarithmic growth in response to low concentrations of hydrogen peroxide. This
      induction is OxyR-dependent. On the other hand, HPII is not peroxide-inducible
      but is induced in entry to the stationary phase. We demonstrate here that E. coli
      displayed higher HPI catalase activity when compared to the cultures that were
      grown in a normal medium, if grown in a medium supplemented with iron-citrate.
      Iron supplementation had no effect on HPII catalase. This increase of HPI
      activity was OxyR-independent and not observed in a Deltafur mutant. The
      physiological significance of the increase of HPI activity is unclear, but it
      appears that the katG gene that codes for HPI catalase is among the genes that
      are regulated by Fur.

PMID- 14659083
TI  - Finding your way to the end: a tale of GDNF and endothelin-3.

PMID- 14659084
TI  - Synaptic inhibition mediated by glia.

PMID- 14659085
TI  - A gradient of single-channel conductance in the cochlea: tuning the cochlea's
      strings?

PMID- 14659086
TI  - Specifying the age-sensitive component of a short-term memory.

PMID- 14659087
TI  - Bringing order to the glutamate chaos in schizophrenia.
AB  - Recent genetic linkage studies complement the existing evidence that implicates
      abnormalities in NMDA receptor-mediated neurotransmission in the pathophysiology
      of schizophrenia. At the same time, advances in our understanding of the complex
      mechanisms that modulate the function of NMDA receptors suggest several novel
      sites for pharmacological manipulation of these receptors. This presents exciting
      opportunities for rational rather than serendipitous discovery of therapeutics
      for schizophrenia.

PMID- 14659088
TI  - Diffusion MRI of complex neural architecture.
AB  - While functional brain imaging methods can locate the cortical regions subserving
      particular cognitive functions, the connectivity between the functional areas of
      the human brain remains poorly understood. Recently, investigators have proposed
      a method to image neural connectivity noninvasively using a magnetic resonance
      imaging method called diffusion tensor imaging (DTI). DTI measures the molecular
      diffusion of water along neural pathways. Accurate reconstruction of neural
      connectivity patterns from DTI has been hindered, however, by the inability of
      DTI to resolve more than a single axon direction within each imaging voxel. Here,
      we present a novel magnetic resonance imaging technique that can resolve multiple
      axon directions within a single voxel. The technique, called q-ball imaging, can
      resolve intravoxel white matter fiber crossing as well as white matter insertions
      into cortex. The ability of q-ball imaging to resolve complex intravoxel fiber
      architecture eliminates a key obstacle to mapping neural connectivity in the
      human brain noninvasively.

PMID- 14659089
TI  - Importance of intrinsic mechanisms in cell fate decisions in the developing rat
      retina.
AB  - Cell diversification in the developing nervous system is thought to involve both
      cell-intrinsic mechanisms and extracellular signals, but their relative
      importance in particular cell fate decisions remains uncertain. In the mammalian
      retina, different cell types develop on a predictable schedule from multipotent
      retinal neuroepithelial cells (RNECs). A current view is that RNECs pass through
      a series of competence states, progressively changing their responsiveness to
      instructive extracellular cues, which also change over time. We show here,
      however, that embryonic day 16-17 (E16-17) rat RNECs develop similarly in serum
      free clonal-density cultures and in serum-containing retinal explants--in the
      number of times they divide, the cell types they generate, and the order in which
      they generate these cell types. These surprising results suggest that
      extracellular signals may be less important than currently believed in
      determining when RNECs stop dividing and what cell types they generate when they
      withdraw from the cell cycle, at least from E16-17 onward.

PMID- 14659090
TI  - Enteric nervous system progenitors are coordinately controlled by the G protein
      coupled receptor EDNRB and the receptor tyrosine kinase RET.
AB  - The enteric nervous system (ENS) in vertebrates is derived mainly from vagal
      neural crest cells that enter the foregut and colonize the entire wall of the
      gastrointestinal tract. Failure to completely colonize the gut results in the
      absence of enteric ganglia (Hirschsprung's disease). Two signaling systems
      mediated by RET and EDNRB have been identified as critical players in enteric
      neurogenesis. We demonstrate that interaction between these signaling pathways
      controls ENS development throughout the intestine. Activation of EDNRB
      specifically enhances the effect of RET signaling on the proliferation of
      uncommitted ENS progenitors. In addition, we reveal novel antagonistic roles of
      these pathways on the migration of ENS progenitors. Protein kinase A is a key
      component of the molecular mechanisms that integrate signaling by the two
      receptors. Our data provide strong evidence that the coordinate and balanced
      interaction between receptor tyrosine kinases and G protein-coupled receptors
      controls the development of the nervous system in mammals.

PMID- 14659091
TI  - Temporally distinct requirements for endothelin receptor B in the generation and
      migration of gut neural crest stem cells.
AB  - Loss of Endothelin-3/Endothelin receptor B (EDNRB) signaling leads to
      aganglionosis of the distal gut (Hirschsprung's disease), but it is unclear
      whether it is required primarily for neural crest progenitor maintenance or
      migration. Ednrb-deficient gut neural crest stem cells (NCSCs) were reduced to
      40% of wild-type levels by embryonic day 12.5 (E12.5), but no further depletion
      of NCSCs was subsequently observed. Undifferentiated NCSCs persisted in the
      proximal guts of Ednrb-deficient rats throughout fetal and postnatal development
      but exhibited migration defects after E12.5 that prevented distal gut
      colonization. EDNRB signaling may be required to modulate the response of neural
      crest progenitors to migratory cues, such as glial cell line-derived neurotrophic
      factor (GDNF). This migratory defect could be bypassed by transplanting wild-type
      NCSCs directly into the aganglionic region of the Ednrb(sl/sl) gut, where they
      engrafted and formed neurons as efficiently as in the wild-type gut.

PMID- 14659092
TI  - Rho-dependent contractile responses in the neuronal growth cone are independent
      of classical peripheral retrograde actin flow.
AB  - Rho family GTPases have been implicated in neuronal growth cone guidance;
      however, the underlying cytoskeletal mechanisms are unclear. We have used
      multimode fluorescent speckle microscopy (FSM) to directly address this problem.
      We report that actin arcs that form in the transition zone are incorporated into
      central actin bundles in the C domain. These actin structures are Rho/Rho Kinase
      (ROCK) effectors. Specifically, LPA mediates growth cone retraction by ROCK
      dependent increases in actin arc and central actin bundle contractility and
      stability. In addition, these treatments had marked effects on MT organization as
      a consequence of strong MT-actin arc interactions. In contrast, LPA or
      constitutively active Rho had no effect on P domain retrograde actin flow or
      filopodium bundle number. This study reveals a novel mechanism for domain
      specific spatial control of actin-based motility in the growth cone with
      implications for understanding chemorepellant growth cone responses and nerve
      regeneration.

PMID- 14659093
TI  - The presynaptic release apparatus is functional in the absence of dendritic
      contact and highly mobile within isolated axons.
AB  - Whether contact of an axon with a dendrite is a necessary inductive signal for
      the assembly of functional presynaptic machinery is controversial. Combining FM1
      43 imaging with retrospective immunocytochemistry, we observe many functional
      synaptic vesicle (SV) release sites lacking postsynaptic specializations in
      cultured hippocampal neurons. These "orphan" release sites share the same
      exocytic machinery and mechanisms of endocytic recycling as mature synaptic
      sites. Moreover, quantitative analysis of FM1-43 destaining at these orphan
      release sites reveals similar kinetics with slightly lower release probabilities.
      Time-lapse imaging of FM1-43 reveals that orphans are generated by complete or
      partial mobilization of synaptic release sites that retain their functionality in
      transit. Orphan clusters fuse with existing synaptic release sites or form novel
      release sites onto dendrites. Mobilization and stabilization of orphan boutons to
      new sites of dendritic contact may represent a necessary presynaptic counterpart
      to postsynaptic changes observed during development and plasticity in the CNS.

PMID- 14659094
TI  - Regulation of hyperpolarization-activated HCN channels by cAMP through a gating
      switch in binding domain symmetry.
AB  - Recent X-ray structures show that the binding domains of tetrameric ligand-gated
      channels form either a 4-fold symmetric gating ring or a 2-fold symmetric dimer
      of dimers. To determine how such structures function to coordinate the binding of
      multiple ligands during channel activation, we examined the action of cAMP to
      enhance the opening of the hyperpolarization-activated HCN2 channels, whose
      cytoplasmic C terminus forms a gating ring in the presence of cAMP. Using tandem
      dimers and tetramers in which cAMP binding to selected HCN2 subunits was
      prevented by a point mutation or deletion, we provide the first direct
      determination of the energetic effects on gating of each of four ligand binding
      events and demonstrate the importance of the gating ring for cAMP regulation. We
      suggest that cAMP binding enhances channel opening by promoting assembly of the
      gating ring from an unliganded state in which the four subunits interact as a 2
      fold symmetric dimer of dimers.

PMID- 14659095
TI  - ATP released by astrocytes mediates glutamatergic activity-dependent
      heterosynaptic suppression.
AB  - Extracellular ATP released from axons is known to assist activity-dependent
      signaling between neurons and Schwann cells in the peripheral nervous system.
      Here we report that ATP released from astrocytes as a result of neuronal activity
      can also modulate central synaptic transmission. In cultures of hippocampal
      neurons, endogenously released ATP tonically suppresses glutamatergic synapses
      via presynaptic P2Y receptors, an effect that depends on the presence of
      cocultured astrocytes. Glutamate release accompanying neuronal activity also
      activates non-NMDA receptors of nearby astrocytes and triggers ATP release from
      these cells, which in turn causes homo- and heterosynaptic suppression. In CA1
      pyramidal neurons of hippocampal slices, a similar synaptic suppression was also
      produced by adenosine, an immediate degradation product of ATP released by glial
      cells. Thus, neuron-glia crosstalk may participate in activity-dependent synaptic
      modulation.

PMID- 14659096
TI  - Tonotopic variation in the conductance of the hair cell mechanotransducer
      channel.
AB  - Hair cells in the vertebrate cochlea are arranged tonotopically with their
      characteristic frequency (CF), the sound frequency to which they are most
      sensitive, changing systematically with position. Single mechanotransducer
      channels of hair cells were characterized at different locations in the turtle
      cochlea. In 2.8 mM external Ca2+, the channel's chord conductance was 118 pS
      (range 80-163 pS), which nearly doubled (range 149-300 pS) on reducing Ca2+ to 50
      microM. In both Ca2+ concentrations, the conductance was positively correlated
      with hair cell CF. Variation in channel conductance can largely explain the
      increases in size of the macroscopic transducer current and speed of adaptation
      with CF. It suggests diversity of transducer channel structure or environment
      along the cochlea that may be an important element of its tonotopic organization.

PMID- 14659097
TI  - A cellular mechanism for prepulse inhibition.
AB  - In prepulse inhibition (PPI), startle responses to sudden, unexpected stimuli are
      markedly attenuated if immediately preceded by a weak stimulus of almost any
      modality. This experimental paradigm exposes a potent inhibitory process, present
      in nervous systems from invertebrates to humans, that is widely considered to
      play an important role in reducing distraction during the processing of sensory
      input. The neural mechanisms mediating PPI are of considerable interest given
      evidence linking PPI deficits with some of the cognitive disorders of
      schizophrenia. Here, in the marine mollusk Tritonia diomedea, we describe a
      detailed cellular mechanism for PPI--a combination of presynaptic inhibition of
      startle afferent neurons together with distributed postsynaptic inhibition of
      several downstream interneuronal sites in the startle circuit.

PMID- 14659098
TI  - Aging specifically impairs amnesiac-dependent memory in Drosophila.
AB  - Age-related memory impairment (AMI) is observed in many species. However, it is
      uncertain whether AMI results from a specific or a nonspecific decay in memory
      processing. In Drosophila, memory acquired after a single olfactory conditioning
      paradigm has three distinct phases: short-term memory (STM), middle-term memory
      (MTM), and longer-lasting anesthesia-resistant memory (ARM). Here, we demonstrate
      that age-related defects in olfactory memory are identical to those of the MTM
      mutant amnesiac (amn). Furthermore, amn flies do not exhibit an age-dependent
      decrease in memory, in contrast to other memory mutants. The absence of AMI in
      amn flies is restored by expression of an amn transgene predominantly in DPM
      cells. Thus, we propose that AMI in flies results from a specific decrease in amn
      dependent MTM.

PMID- 14659099
TI  - Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear
      conditioning: mnemonic code or fear bias?
AB  - Amygdala neuroplasticity has emerged as a candidate substrate for Pavlovian fear
      memory. By this view, conditional stimulus (CS)-evoked activity represents a
      mnemonic code that initiates the expression of fear behaviors. However, a fear
      state may nonassociatively enhance sensory processing, biasing CS-evoked activity
      in amygdala neurons. Here we describe experiments that dissociate auditory CS
      evoked spike firing in the lateral amygdala (LA) and both conditional fear
      behavior and LA excitability in rats. We found that the expression of conditional
      freezing and increased LA excitability was neither necessary nor sufficient for
      the expression of conditional increases in CS-evoked spike firing. Rather,
      conditioning-related changes in CS-evoked spike firing were solely determined by
      the associative history of the CS. Thus, our data support a model in which
      associative activity in the LA encodes fear memory and contributes to the
      expression of learned fear behaviors.

PMID- 14659100
TI  - Area-specific amblyopic effects in human occipitotemporal object representations.
AB  - The role of early visual experience in the establishment of human high-order
      visual areas is poorly understood. Here we investigated this issue using human
      amblyopia--a developmental visual disorder, which manifests a central vision
      (acuity) deficit. Previous fMRI studies of amblyopes have described abnormal
      functional activations in early retinotopic areas. Here we report the surprising
      finding of a selective object-related abnormality in high-order occipitotemporal
      cortex. Specifically, we found that face-related cortical areas show a severe
      disconnection from the amblyopic eye, while building-related regions remain
      essentially normal. The selectivity of the deficit highlights the differential
      computations performed in the different object-related areas and is compatible
      with the suggested association of face regions with analysis of fine detail.

PMID- 14659101
TI  - Saccade reward signals in posterior cingulate cortex.
AB  - Movement selection depends on the outcome of prior behavior. Posterior cingulate
      cortex (CGp) is strongly connected with both limbic and oculomotor circuitry, and
      CGp neurons respond following saccades, suggesting a role in signaling the
      motivational outcome of gaze shifts. To test this hypothesis, single CGp neurons
      were studied in monkeys while they shifted gaze to visual targets for liquid
      rewards that varied in size or were delivered probabilistically. CGp neurons
      responded following saccades as well as following reward delivery, and these
      responses were correlated with reward size. CGp neurons also responded following
      the omission of predicted rewards. The timing of CGp activation and its
      modulation by reward could provide signals useful for updating representations of
      expected saccade value.

PMID- 14659102
TI  - Humor modulates the mesolimbic reward centers.
AB  - Humor plays an essential role in many facets of human life including
      psychological, social, and somatic functioning. Recently, neuroimaging has been
      applied to this critical human attribute, shedding light on the affective,
      cognitive, and motor networks involved in humor processing. To date, however,
      researchers have failed to demonstrate the subcortical correlates of the most
      fundamental feature of humor-reward. In an effort to elucidate the
      neurobiological substrate that subserves the reward components of humor, we
      undertook a high-field (3 Tesla) event-related functional MRI study. Here we
      demonstrate that humor modulates activity in several cortical regions, and we
      present new evidence that humor engages a network of subcortical regions
      including the nucleus accumbens, a key component of the mesolimbic dopaminergic
      reward system. Further, the degree of humor intensity was positively correlated
      with BOLD signal intensity in these regions. Together, these findings offer new
      insight into the neural basis of salutary aspects of humor.

PMID- 14659103
TI  - The importance of evidence-based international consensus in the primary treatment
      of breast cancer--a periodic 'must'.

PMID- 14659105
TI  - Prophylactic mastectomy: the Rotterdam experience.
AB  - The efficacy of prophylactic mastectomy (PM) depends on the ability to remove all
      breast tissue and a regular mastectomy is recommended. In our study population
      (n=112), 103 women (94%) have chosen for immediate breast reconstruction (IBR)
      with a silicone prosthesis placed in a subpectoral pocket. The median follow-up
      after IBR was 3.5 (range 1-7) years. These 103 patients underwent 193 PM with
      IBR: 90 bilateral and 13 unilateral. The median follow-up after IBR was 3.5
      (range 1-7) years. In 163 IBRs (82%) no complications were observed. The most
      common late complication was capsular contracture, significantly more around
      prostheses placed in a previously irradiated area. No cases of breast cancer were
      found after PM at a mean follow-up of 2.9 years. After breast cancer a delayed
      ipsilateral PM and/or contralateral PM can be considered after a disease-free
      interval of 2 years, also taking into account the age of onset of the first
      breast cancer. The prognosis of breast cancer in BRCA2 mutation patients seems to
      be similar to that in sporadic cancer. The most striking result of PM is the
      decrease of anxiety of developing breast cancer and a negative impact on their
      sexual life. Therefore a time delay is necessary to allow women to fully address
      the issues involved in PM and IBR.

PMID- 14659104
TI  - Mammographic breast cancer screening: after the dust has settled.

PMID- 14659106
TI  - Growth factor receptor cross-talk with estrogen receptor as a mechanism for
      tamoxifen resistance in breast cancer.
AB  - Breast cancer growth is regulated by steroid hormones and by polypeptide hormones
      and growth factors. Endocrine therapies for breast cancer have been designed to
      interrupt estrogen signaling by either blocking its receptor (ER) or by lowering
      the amount of estrogen available in the cell for binding. These therapies are
      very effective in many patients but de novo and acquired resistance are common.
      Growing evidence suggests that cross-talk between ER and growth factor receptor
      pathways contributes to the development of this resistance. Signaling via the EGF
      receptor and HER-2/neu can activate both ER and the important ER coactivator
      AIB1. In turn, ER located in the cell membrane can activate the growth factor
      receptor pathways. Breast tumors with high levels of AIB1 and HER-2 may be
      resistant to tamoxifen because of an increase in its estrogen agonist activity.

PMID- 14659107
TI  - New findings about endocrine therapy for breast cancer.
AB  - For over a decade, the selective estrogen receptor modulator, tamoxifen, has been
      the primary agent for adjuvant endocrine therapy for steroid receptor-positive
      breast cancer. New data over the last 2 years now suggest that its primacy may be
      challenged by strategies that lower circulating and/or intratumoral estrogens.
      Recent trials support the use of ovarian suppression approaches with or without
      tamoxifen in place of chemotherapy in premenopausal women. A large randomized
      trial has also established the short-term efficacy and safety of the aromatase
      inhibitor, anastrozole, in postmenopausal women. How and when to integrate these
      new approaches into standard practice are topics of debate. Ongoing research is
      focused on choice of endocrine approach, duration and sequencing of endocrine
      treatment, identification of better predictive markers for hormone response, and
      assessment of long-term risks and benefits.

PMID- 14659108
TI  - New data on chemotherapy in the adjuvant setting.
AB  - In the last few months, there have been three sets of new, provocative data that
      might have important implications for the daily prescription of adjuvant
      chemotherapy (CT) in the future. (1) Urokinase-type plasminogen activator (UPA)
      and type 1 plasminogen activator inhibitor (PAI-1), two molecular markers of
      invasion already known for their powerful prognostic value in node-negative
      breast cancer, seem to predict for enhanced benefit from adjuvant CT, while the
      benefit from adjuvant endocrine therapy seems independent of them. The predictive
      value of these markers, however, remains suboptimal and an important limitation
      lies in their evaluation through a cytosolic assay, which is compromised for
      small tumours (<1cm). (2) Breast cancer 'gene expression profiles' have been
      identified through DNA-microarray technology and seem to be better predictors of
      clinical outcome in young women (less than 55 years old) with stage I or II
      breast cancer, when compared to the currently used clinical-pathological
      criteria. Remarkably, these molecular data suggest that the prognostic profile of
      breast cancer does not depend on lymph node status and that it is possible to
      identify a group of node-positive breast cancer patients with an unexpectedly
      good prognosis. Prospective and independent confirmation is needed, but these
      data are fascinating and carry the hope that CT decision-making in breast cancer
      will be greatly facilitated in the future. (3) The recently reported CALGB 9741
      (or INT 69741) trial shakes our belief that 'one cycle of CT every 3 weeks' is
      the adequate adjuvant treatment for node-positive breast cancer. Launched in
      1999, it aimed to test two novel concepts based on mathematical models of tumour
      cell growth kinetics. Concept 1 implies that dose-densification of CT, i.e.,
      delivering drugs at reduced intervals, will maximize the chances of eradicating
      the tumour; and concept 2 extends the first one to encompass situations of
      heterogeneous drug sensitivity through the use of sequential dose-dense, non
      cross-resistant single agents or regimens. The 3-year results of this trial
      strongly support concept 1; a longer follow-up and a confirmation study are
      desirable before recommending changes in routine patient care.

PMID- 14659109
TI  - Pharmacological prevention of breast cancer: quo vadis?
AB  - Although tamoxifen reduces breast cancer incidence by 30-40% in at-risk subjects,
      its adverse events may be a limiting factor. Thus, different strategies are being
      pursued to improve the risk:benefit ratio of breast cancer chemoprevention
      intervention. Firstly, raloxifene is being compared with tamoxifen in a phase-III
      trial, whereas the minimal active dose of tamoxifen is being assessed in phase I
      II trials. The combination of HRT and tamoxifen may also reduce the risks while
      retaining the benefits of either agent. Anastrozole holds promise as a preventive
      agent based on preliminary data on contralateral breast cancer. Another important
      area is the appropriate identification of women at increased risk for ER-positive
      breast cancer due to reproductive factors, which may maximize the therapeutic
      index of hormonal agents. Finally, new targets that interfere with the onset of
      ER-negative breast cancer are being sought since one-third of breast cancers will
      not be modulated by hormonal interventions.

PMID- 14659110
TI  - The new TNM classification and micrometastases.
AB  - The 6th Edition of the TNM classification is considered with particular reference
      to the evidence base for the analysis of lymph nodes. The justification for the
      definition of a micrometastasis is considered and in particular the problems
      related to describing a node deposit of less than 200 microm as NO. Such a
      classification in the absence of clear instructions on node examination is of
      limited value in terms of comparing different centres and even within the same
      centre. The classification does not embrace the rapid advances in the biology of
      breast cancer and some of these are considered as possible ways forward. TNM is
      meant to be pragmatic and evidence based leading to indications for treatment and
      a uniform approach between centres. In the former it succeeds, but some of the
      definitions would appear to be based on limited established data.

PMID- 14659111
TI  - Histopathology of primary breast cancer 2003.
AB  - The histologic and immunophenotypic characterisation of primary breast carcinoma
      admittedly is a finite and imperfect source of information for an ideal
      prognostic and predictive evaluation, and for tailoring the most appropriate
      adjuvant intervention for each individual patient. Complementary data coming from
      molecular profiling assays hopefully will significantly add to our current skills
      in predicting the future. Undoubtedly, however, the traditional morphological and
      immunohistochemical features are the faithful mirror of the differential
      expression of hundreds of genes, which may therefore be safely and consistently
      evaluated even by simple histologic examination and immunohistochemical assays.
      What is nowadays especially needed is to improve our skills and technical means
      for assuring accuracy and reproducibility of the morphological and
      immunohistochemical findings.

PMID- 14659112
TI  - Evaluation of bone marrow in breast cancer patients: prediction of clinical
      outcome and response to therapy.
AB  - Blood-borne distant metastasis is the leading cause of cancer-related death in
      breast cancer. The onset of this fundamental process can now be assessed in
      cancer patients by using ultrasensitive immunocytochemical and molecular assays
      able to detect even single metastatic cells. To date, clinical studies with large
      study populations, validated immunoassays, and adequate follow-up time provide
      evidence for the independent prognostic value of the presence of disseminated
      tumor cells in the bone marrow. At present, bone marrow evaluation may therefore
      be considered a diagnostic tool for improved risk assessment with regard to
      distant relapse and death, especially among potentially curable breast cancer
      patients. Except for promising pilot studies, no data are available to support
      the immediate use of bone marrow evaluation for treatment monitoring in order to
      enable the prediction of response to adjuvant therapy.

PMID- 14659113
TI  - Epidemiology of breast cancer--selected highlights.
AB  - The main risk factors for breast cancer can be usefully grouped into four major
      categories-family history/genetic, reproductive/hormonal, proliferative benign
      breast pathology, and mammographic density. These factors are briefly reviewed
      and quantitative estimaters of risk are given. A computer programme for combining
      them to produce individualized risk profiles is described. The ongoing IBIS-II
      trial of chemoprevention for high risk postmenopausal women is presented as one
      approach to managing high risk women.

PMID- 14659115
TI  - Breast cancer in the media--friend or enemy?

PMID- 14659114
TI  - Nutrition and breast cancer.
AB  - The major risk factors for breast cancer are hormone-related, and the only well
      established diet-related risk factors for breast cancer are obesity and alcohol
      consumption. Obesity increases breast cancer risk in postmenopausal women by
      around 30%, probably by increasing serum concentrations of bioavailable
      oestradiol. Moderate alcohol intakes increase breast cancer risk by about 7% per
      alcoholic drink per day, perhaps also by increasing oestrogen levels. Populations
      with high fat intakes generally have high rates of breast cancer, but studies of
      individual women have not confirmed an association of high fat diets with breast
      cancer risk. Phyto-oestrogens can affect hormone metabolism, but data on phyto
      oestrogen consumption and breast cancer risk are inconsistent. Nutrition might
      affect breast cancer risk by altering levels of growth factors such as insulin
      like growth factor-I. Current dietary advice should be to avoid obesity, limit
      alcohol intake, and maintain a varied diet.

PMID- 14659116
TI  - The role of women's advocacy groups in breast cancer.

PMID- 14659117
TI  - Internet and information on breast cancer: an overview.
AB  - In the past few years, many Internet breast cancer resources have appeared,
      including medical journals and clinical trial registries. Examples of online
      breast cancer journals are the The Breast, The Breast Journal, and the Breast
      Cancer Research and Treatment. These have replicated the experience of general
      medical and cancer journals such as the British Medical Journal and the Journal
      of Clinical Oncology. One of the most important cancer registries is the
      Physician Data Query, which provides information on the National Cancer
      Institute's clinical trials, most of which are related to breast cancer. Medical
      guideline databases, institutional websites, medical associations, and non-profit
      breast cancer organizations provide users with information including news,
      calendars of international breast cancer events, clinical guidelines and
      abstracts presented at cancer and breast cancer meetings. Finding high-quality
      breast cancer literature and websites is relatively easy using appropriate
      indexes such as Cancerlit, MedlinePlus, and Cancerlinks.

PMID- 14659118
TI  - Changing role of the oestrogen receptor in the life and death of breast cancer
      cells.
AB  - The oestrogen receptor (ER) has proven to be an extraordinarily successful target
      for breast cancer treatment and prevention. The clinical use of tamoxifen, a
      nonsteroidal antioestrogen, demonstrated (1) that the strategic use of adjuvant
      tamoxifen in ER-positive patients could save lives and (2) that a selective ER
      modulator (SERM) could reduce the incidence of breast cancer in high-risk women.
      The ER is now the target for new and safer therapies such as the aromatase
      inhibitors and the pure antioestrogens that either block oestrogen synthesis or
      destroy the ER. However, the use of raloxifene, a SERM to prevent osteoporosis
      with the potential to prevent breast cancer has introduced a new dimension into
      preventive oncology. The widespread use of endocrine modulators (SERMs, aromatase
      inhibitors, and pure antioestrogens) raised the question of drug resistance. It
      is now clear that endocrine resistance can evolve through stages. Once a breast
      tumour becomes resistant to SERMs, the growth is stimulated by either the SERM or
      oestrogen. This is why an aromatase inhibitor is effective following SERM
      resistance and withdrawal. However, the extended use of repeated endocrine
      therapies now supersensitized the cells to oestrogen that causes apoptosis
      through the ER. We suggest that future clinical treatment strategies incorporate
      an 'oestrogen purge' to both enhance the actions of chemotherapy or completely
      reverse endocrine resistance and restore endocrine sensitivity. These new data
      build on the idea that breast cancer can be controlled as a chronic disease and
      will permit patients to live long and productive lives during targeted
      maintenance treatment.

PMID- 14659119
TI  - Efforts to link biological and clinical breast cancer research.
AB  - Important issues that underpin efforts to link new biological data on breast
      cancer to clinical research are considered. While animal models have been helpful
      in drug development, the changes in some key markers (oestrogen receptor and
      Ki67) in response to hormonal therapy are very different in patients. To predict
      that benefit of therapy in biomarker-defined subgroups requires the parallel
      study of a randomized control arm. Biomarker analyses have reduced statistical
      power compared with whole trials. Neoadjuvant therapy is an advantageous scenario
      to link biological and clinical research.

PMID- 14659120
TI  - Ductal carcinoma in situ: surgery and radiotherapy.
AB  - As a consequence of mammographic breast screening programmes, ductal carcinoma in
      situ is diagnosed with increasing frequency. There are widely disparate
      philosophies concerning diagnosis, classification and treatment. This review
      discusses the management of DCIS in light of the new data from randomised trials.

PMID- 14659121
TI  - The risk of a contralateral breast cancer among women diagnosed with ductal and
      lobular breast carcinoma in situ: data from the Connecticut Tumor Registry.
AB  - BACKGROUND: Women diagnosed with breast carcinoma in situ are at increased risk
      for developing a contralateral breast cancer. The magnitude of this risk and the
      relationship between this risk and age, time since diagnosis, histologic subtype,
      and treatment for the first breast cancer is continuing to be defined. METHODS:
      The risk of developing a contralateral breast cancer is examined among 4198 women
      diagnosed with breast carcinoma in situ and reported to the Connecticut Tumor
      Registry (CTR) between January 1, 1975 and March 14, 1998 using Kaplan-Meier
      estimation. A Cox proportional hazards model is used to assess the effect of
      surgical treatment, radiation therapy, age at diagnosis, race, histology, marital
      status, anatomic location within the breast, and time since diagnosis upon this
      risk. RESULTS: The cumulative 5- and 10-year probabilities of being diagnosed
      with a contralateral breast cancer among women initially diagnosed with a ductal
      breast carcinoma in situ (DCIS) were 4.3% (95% confidence interval, 3.6-5.0%) and
      6.8% (95% confidence interval, 5.5-8.2%), respectively. These risks are 3.35
      times greater than those for women without a history of breast cancer but are
      similar to those for women diagnosed with non-metastatic invasive ductal
      carcinomas of the breast. The cumulative 5- and 10-year probabilities of being
      diagnosed with a contralateral breast cancer among women initially diagnosed with
      a lobular breast carcinoma in situ (LCIS) were 11.9% (95% confidence interval,
      9.5-14.3%) and 13.9% (95% confidence interval, 11.0-16.8%), respectively.
      CONCLUSIONS: Women diagnosed with LCIS were 2.6 (95% confidence interval, 2.0
      3.4%) times more likely than women with DCIS to be diagnosed with a contralateral
      breast cancer within the first six months of the first breast primary. The risk
      of developing a contralateral breast cancer more than 6 months after the initial
      breast cancer was independent of surgical or radiation therapy, time since
      diagnosis, age at diagnosis, histology, race, marital status, or anatomic
      location of the cancer within the breast.

PMID- 14659122
TI  - Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin
      status.
AB  - As our knowledge of ductal carcinoma in situ (DCIS) continues to evolve,
      treatment decision-making has become increasingly complex and controversial for
      both patients and physicians. Treatment options include mastectomy, and breast
      conservation with or without radiation therapy. Data produced from the randomized
      clinical trials for DCIS has provided the basis for important treatment
      recommendations, but are not without limitations. In this article, we review our
      prospectively collected database consisting of 1036 patients with DCIS treated at
      the Van Nuys Breast Center and the USC/Norris Comprehensive Cancer Center. We
      review the use of the USC/Van Nuys Prognostic Index, a clinical algorithm
      designed to assist physicians in selection of appropriate treatments, and examine
      the impact of margin status as a sole predictor of local recurrence.

PMID- 14659123
TI  - The future of surgery in the treatment of breast cancer.
AB  - The role of surgery cannot be discussed independently, but in relationship to the
      other modalities of treatment. Sentinel lymph node mapping and biopsy has
      revolutionized the role of surgery in axillary staging. Techniques of sentinel
      node mapping, the timing relative to chemotherapy, possible contraindications,
      and the necessity of completion axillary dissection are all under active
      investigation. The next few years will see continued changes in this important
      technique. Techniques of localizing clinically occult tumors are numerous and
      under study. These are not yet at the level of Phase III comparative trials.
      Induction chemotherapy has long been standard care for women with locally
      advanced breast cancer. It has not become standard care for Stage I or II breast
      cancers that meet criteria for adjuvant therapy. The ability to significantly
      downsize 80% of breast cancers is reason enough to make it usual practice for
      women who are certain to receive chemotherapy, if only for the cosmetic advantage
      that would accrue. Much has been made of the use of thermal ablation of small
      breast cancers by small probes introduced by skin puncture. In initial trials the
      lesions were excised after being heated or frozen. Current studies are leaving
      the destroyed tissue in place and following for evidence of control or
      recurrence. The value of this approach in terms of cosmesis is unproven, and the
      timing of its introduction when small tumors are being evaluated for margins and
      genetic markers, make it difficult to imagine broad acceptance. Finally, the role
      of prophylactic surgery for women at increased risk remains a difficult equation,
      compounded of alternatives such as chemoprevention, availability and
      effectiveness of surveillance techniques, and the level of fear and anxiety of
      the patient.

PMID- 14659124
TI  - Radiotherapy to the conserved breast, chest wall, and regional nodes: is there a
      standard?
AB  - BACKGROUND: The role of radiotherapy in the treatment of breast cancer has
      changed considerable during the last two decades. It has now become the standard
      part of the breast-conserving procedure, as well as in patients who underwent
      mastectomy with T3+tumor and/or 4 or more positive lymphnodes in axilla. METHODS:
      Improvements are seen in the postmastectomy radiotherapy area by delivering
      better treatment techniques herewith avoiding treatment of the heart and lungs in
      order to optimize the improvement of local control and the significant
      improvement in survival. Indications exist that the largest impact of
      postmastectomy radiotherapy on survival is mostly seen in patients with minimal
      tumorload, i.e. small tumors and/or 1 or 2 positive lymphnodes. RESULTS: In
      several clinical trials, it was shown that the relapse rate in the ipsilateral
      breast is reduced with a HR of 4 if whole breast irradiation is given after
      tumorectomy. The update of the Oxford meta-analysis demonstrated that this
      improvement in local control has also led to an improved survival in these
      patients. More information is recently gained on the required radiation dose in
      breast-conserving therapy. Especially patients less than 50 years of age have to
      be treated with a high radiation dose, 50 + 16 Gy boost, while a dose of 50 Gy in
      5 weeks seems sufficient for patients older than 50 years, who have a
      microscopically complete excision. Further optimization of the radiotherapy
      technique is found in imaged guided approaches and intensity modulated
      radiotherapy. Combining these efforts allows for a more precise delivery of the
      radiation dose to a limited volume, so that the side effects like fibrosis will
      be reduced. CONCLUSIONS: Partial breast irradiation, instead of whole breast
      irradiation, is now being tested in a few randomized trials. Although this
      approach may be useful in certain patients groups, it still cannot be accepted as
      standard treatment, as no proper selection criteria exist and no long-term follow
      up data have been presented.

PMID- 14659125
TI  - Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast
      cancer.
AB  - Local recurrences after breast-conserving surgery occur mostly in the quadrant
      harbouring primary carcinoma. The main objective of postoperative radiotherapy
      should be the sterilisation of residual cancer cells in the operative area while
      irradiation of the whole breast may be avoided. We have developed a new technique
      of intraoperative radiotherapy of a breast quadrant after the removal of the
      primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is
      utilised delivering electron beams able to produce energies from 3 to 9 MeV.
      Different dose levels were tested from 10 to 21 Gy without important side
      effects. A randomized trial is currently ongoing in order to compare conventional
      irradiation and ELIOT. More than 400 patients have been enrolled. In addition a
      new approach for nipple and areola complex conservation, including ELIOT, is
      under investigation.

PMID- 14659126
TI  - MammoSite radiation therapy system.
AB  - The MammoSite Radiation Therapy System (RTS) has become the most widely used
      brachytherapy method used in the treatment of breast cancer, due to its ease of
      use, short learning curve, and requirement of only one interstitial path through
      the breast skin. The dosimetry is simple, one source position in the middle of
      the MammoSite balloon catheter. The data on long-term complications, however are
      not available, though developing. Trials for DCIS are being developed, as well as
      a comparison trial to standard external beam radiation as well as other forms of
      accelerated partial breast irradiation (APBI).

PMID- 14659127
TI  - The best use of adjuvant endocrine treatments.
AB  - Endocrine therapy remains important in the adjuvant treatment of pre- and
      postmenopausal women. Adjuvant ovarian ablation with or without tamoxifen
      produces effects which are equivalent to those of CMF (cyclophosphamide,
      methotrexate and 5-fluorouracil) chemotherapy in premenopausal women with
      oestrogen receptor (ER) and/or progesterone receptor (PgR) positive breast
      cancer. Tamoxifen alone is also effective in these women. Concurrent use of
      tamoxifen and ovarian ablation may be even more effective, but more studies are
      needed. Tamoxifen remains a standard adjuvant therapy for postmenopausal women
      with ER and/or PgR positive tumours. Current information supports the use of 5
      years of tamoxifen but additional studies comparing 5 years to longer duration
      are ongoing. The aromatase inhibitor (AI) anastrozole has now been demonstrated
      to be better than tamoxifen in preventing recurrence in early reports from the
      Arimidex vs Tamoxifen And the Combination (ATAC) Trial. Ongoing trials of this
      and other AIs before, after, concurrent with, or substituted for tamoxifen in the
      adjuvant setting may soon revolutionize our approach for postmenopausal women.
      Adjuvant bisphosphonates have been shown to reduce the incidence of bone
      metastases and improve survival in two of three published adjuvant trials and are
      being further studied. Her-2 neu status is being explored as a predictive factor
      for selection of endocrine therapy, but is not yet considered standard for this
      purpose.

PMID- 14659128
TI  - Adjuvant endocrine therapy for the very young patients.
AB  - Breast cancer is rare before age 40. Sixty to seventy percent of breast cancers
      in this age group express estrogen or progesterone receptors. All following
      considerations refer to endocrine responsive disease. Ovarian ablation reduces
      the relative risk of recurrence and death by at least one quarter in the absence
      of chemotherapy. Chemotherapy induced amenorrhea reduces the risk of recurrence
      and death when compared to patients with continuing menses. Chemotherapy is
      insufficient therapy for very young patients with hormone responsive disease,
      particularly if chemotherapy fails to induce amenorrhea. Tamoxifen is effective
      in young patients even in combination with chemotherapy. The ablation or
      suppression of ovarian function was equivalent to chemotherapy in at least eight
      randomized trials. Preliminary evidence is compatible with an additional adjuvant
      effect of LHRH agonists after chemotherapy, particularly in women < 40 years of
      age. Young patients with endocrine responsive tumors should be treated on a
      clinical trial. If this is impossible, they should receive tamoxifen and either
      an LHRH agonist or chemotherapy or both.

PMID- 14659129
TI  - Prognostic influence of pregnancy before, around, and after diagnosis of breast
      cancer.
AB  - A woman's risk of developing breast cancer is closely related to reproductive
      factors. Whereas the etiological importance of reproductive factors is well
      described, less is known about the prognostic influence of these factors. The
      prognostic effect of childbearing before, around, and after diagnosis is reviewed
      based on the literature and on studies from Danish Breast Cancer Cooperative
      Group, DBCG. In women with breast cancer overall number of childbirths is found
      to be without prognostic importance. Women with early primary childbirth seem to
      have an inferior prognosis compared to women who postpone childbearing. It is
      generally accepted that early first childbirth is associated with reduced risk of
      developing breast cancer. Thus, it is proposed that women who develop breast
      cancer despite an early first delivery represent a selected group of patients
      with particularly aggressive disease. Women diagnosed with breast cancer during
      pregnancy often present with advanced disease, but pregnancy at time of diagnosis
      does not seem to be an independent prognostic factor. However, women diagnosed
      with breast cancer in the first years after childbirth have a significantly
      reduced survival. It is assumed that these women, due to the physiological
      changes during pregnancy, experience growth induction of the tumours during the
      preclinical stage. In contrast, there is no evidence that pregnancy after breast
      cancer treatment has a negative influence on prognosis.

PMID- 14659130
TI  - The best use of chemotherapy in the adjuvant setting.
AB  - Currently, based on the results of large randomized clinical trials and the
      conclusions of the Oxford meta-analysis (EBCTCG. Lancet 1998; 352: 930; Peto R.
      Fifth Main Meeting of the Early Breast Cancer Trialist's Collaborative Group,
      Oxford, UK, September 2000) and following internationally accepted treatment
      guidelines (National Institutes of Health Consensus Development Panel. J Natl
      Cancer Inst 2001; 93(13): 979; Goldhirsch et al. J Clin Oncol 2001; 19: 3817),
      the vast majority of primary breast cancer patients is offered adjuvant medical
      therapy. Regarding adjuvant chemotherapy (CT), the two most important and
      challenging tasks of the medical oncologist today are (1) to identify who needs
      CT and (2) to select the CT regimen that will work best for the individual
      patient, while at the same time minimizing the risk of severe or permanent
      toxicities. The second question will be the focus of this paper.

PMID- 14659131
TI  - Best use of adjuvant systemic therapies II, chemotherapy aspects: dose of
      chemotherapy-cytotoxicity, duration and responsiveness.
AB  - The overall survival improvement by adjuvant chemotherapy is partly related to
      patient age, stage and chemotherapy regimens used. Too low dose dose-intensities
      or total doses will result in inferior outcomes. Conventional dose escalations
      above standard doses will not be beneficial for doxorubicin or cyclophosphamide,
      while an epirubicin dose of 90-100mg/m2 given every third week in
      polychemotherapy regimens results in overall survival gains. The issue is more
      complex, while retrospective analysis of adjuvant regimens have revealed inferior
      outcomes for patients receiving standard chemotherapy doses and regimens without
      toxicity. Most cytostatics demonstrate a marked inter-individual variation in
      different pharmacokinectic parameters, not compensated for by dosage based on
      body surface area. These facts have partly been the basis for the randomised
      Scandinavian Breast Group (SBG) studies SBG 9401 and 2000-1, respectively, using
      tailored dosage strategies aiming at interpatient equivalent dosage. Randomised
      studies using marrow supported-high dose strategies have so far not been
      demonstrated to result in overall survival improvements. G-CSF (granulocyte
      colony stimulating factor) and dose-dense paclitaxel containing regimens have
      resulted in a small but significant survival gain compared with conventional
      three weekly regimens, challenging the present dogma of conventional three-four
      weekly scheduling, based on normal tissue side-effects rather than tumour
      biological considerations. The recent microarray based studies demonstrated
      marked inter-patient variability in gene expression and underline the potential
      for better patient selection and more tailored therapy strategies.

PMID- 14659132
TI  - Preoperative systemic treatment: prediction of responsiveness.
AB  - The use of predictive factors allows a more effective use of available therapies
      by enabling clinicians to distinguish patients likely to obtain substantial
      benefit from treatment from those for whom the same therapy is less likely to be
      effective. A most relevant aspect of clinical research is thus to develop
      alternative therapeutic approaches which are more efficacious for this latter
      group, particularly important since treatment effects are likely to be small. In
      the preoperative setting several predictors of response were identified. They
      include: diameter of the lesion (larger lesions respond less than smaller
      lesions), MIB-1 increased expression associated with increased response to
      chemotherapy, and estrogen receptor (ER) and progesterone receptor (PgR)
      expression in the tumor typically associated with increased response to endocrine
      therapies. Other factors include HER-2/neu overexpression, which is a target for
      treatment with the humanized monoclonal antibody against its extracellular
      domain, is hypothesized to increase response to anthracycline combination
      chemotherapy and to lead to an improved response to some endocrine agents (e.g.
      letrozole) rather than to others. Although primary endocrine therapy demonstrated
      activity and low profile of side effects in selected populations of older
      patients, it is infrequently used. On the other hand, chemotherapy remains the
      mainstay of treatment being considered to be a more active and better documented
      option. Experience at the European Institute of Oncology on 399 patients with
      large or locally advanced breast cancer (cT2-T4, N0-2, M0) treated with primary
      chemotherapy, indicated that a proper selection of primary treatment should be
      based on tumor characteristics such as ER and PgR status. In particular, patients
      with tumors with no ER and PgR expression (endocrine-unresponsive disease) at the
      baseline core-biopsy had a significantly higher response rate to chemotherapy if
      compared with tumors with some ER/PgR expression. In fact, the absence of ER and
      PgR expression was the strongest predictors of pCR at the multivariate analysis
      (P<0.0001). Information on endocrine responsiveness before primary systemic
      therapy will lead to better tailoring of treatment modalities, thus avoiding
      chemotherapy in selected populations where other approaches (e.g. endocrine
      primary therapy) might be more useful.

PMID- 14659133
TI  - Markers of increased risk for failure of adjuvant therapies.
AB  - Mortality from breast cancer has been declining in the Western World since 1985.
      Arguably, widespread application of effective adjuvant systemic therapy has been
      a considerable contributing factor. Data from individual trials and the Oxford
      Overview Meta-analyses demonstrate that both endocrine and chemotherapy are
      associated with significant and substantive proportional reductions in annual
      hazard rates of relapse and death. These statistics raise the question: Should
      all patients be treated with all therapies in order to ensure an ongoing sharp
      decline in breast cancer mortality? The answer to this question depends on the
      perspectives of the patient, her caregiver, and her society towards the relative
      toxicities and benefits of therapy. If a patient is willing to accept toxicities
      for any benefit, then the answer is yes. However, if a woman is willing to forego
      some benefit to avoid the toxicities of therapy, then the clinician should
      carefully use well-validated prognostic and predictive factors to help the
      patient select her most acceptable treatment plan.

PMID- 14659134
TI  - Adjuvant therapy for older women with breast cancer.
AB  - The major risk factor for breast cancer is increasing age and more than half of
      all breast cancers in affluent nations occur in women 65 years and older. Co
      morbidity is a key consideration in offering systemic adjuvant treatment to older
      women since significant co-morbidity minimizes the potential value of any
      adjuvant therapy. Tamoxifen has clearly been shown to significantly decrease the
      risk of recurrence and improve survival in women of all ages who have estrogen
      (ER) or progesterone receptor (PR) positive invasive breast cancer, including
      those 70 years and older. Chemotherapy in older patients can improve survival but
      adds little to tamoxifen in women with node-negative, ER+ or PR+ tumors: it
      should be reserved for older women who have reasonable life-expectancy and larger
      node-negative tumors, or node-positive tumors. Ageism is still a barrier to
      clinical trials participation and clinical trials focusing on older women are
      needed.

PMID- 14659135
TI  - Tailoring adjuvant treatments for the individual breast cancer patient.
AB  - BACKGROUND: Chemotherapy, tamoxifen and ovarian function suppression have all
      demonstrated their effectiveness for treating women with early breast cancer.
      Treatment selection for individual patients, however, requires estimates on the
      magnitude of treatment effects to be achieved from the application of each
      modality. Unfortunately, information currently available is insufficient to
      properly tailor adjuvant treatments. METHODS: We consider predictive factors to
      improve our understanding about selection of adjuvant therapies, reassessment of
      data from previous clinical trials and design of future studies. RESULTS:
      Estrogen receptor (ER) and progesterone receptor (PgR) are the primary measures
      available today to tailor adjuvant therapies. Patient age/menopausal status
      (ability to obtain treatment effects via ovarian function suppression), measures
      of the metastatic potential of the tumor (such as number of positive axillary
      lymph nodes), and concurrent use of chemotherapy and tamoxifen are other factors
      that modify the magnitude of relative effect associated with chemotherapy and
      endocrine therapies. The Subpopulation Treatment Effect Pattern Plots (STEPP)
      method displays the patterns of treatment effects within randomized clinical
      trials or datasets from meta-analyses to identify features that predict
      responsiveness to the treatments under study without relying on retrospective
      subset analysis. Confirmation of hypotheses using independent clinical trial
      databases is recommended. DISCUSSION: All findings from clinical trials and meta
      analyses should be presented primarily according to steroid hormone receptor
      status and patient age. Future studies should be designed as tailored treatment
      investigations, with endocrine therapies evaluated within populations of patients
      with endocrine responsive tumors, and chemotherapy questions focused within
      populations of patients with endocrine nonresponsive disease.

PMID- 14659136
TI  - Comments on the St. Gallen Consensus 2003 on the Primary Therapy of Early Breast
      Cancer.
AB  - This final paper of the proceedings of the recent Eighth St. Gallen Conference
      2003 on the Primary Therapy of Early Breast Cancer comments on the Consensus
      Paper put forth by the international expert panel and emphasizes new information,
      that has emerged during the 2 years since the seventh such meeting in 2001. More
      than 3200 breast cancer specialists from various medical fields-coming from 75
      countries and all six continents-have attended the meeting and the process of
      scientific consensus development. Recommendations for patient care are so
      critically dependent on assessment of endocrine responsiveness that the
      importance of high-quality steroid hormone receptor determination and
      standardized quantitative reporting cannot be overemphasized. The Panel modified
      and simplified the risk categories so that only endocrine receptor-absent status
      was sufficient to reclassify an otherwise low-risk, node-negative disease into
      the category of average risk. Absence of steroid hormone receptors was also
      recognized as indicating endocrine non-responsiveness. Some important areas
      highlighted especially in the 2003 consensus include: recognition of the separate
      nature of endocrine non-responsive breast cancer, both invasive cancers and
      ductal carcinoma in situ (DCIS); improved understanding of the mechanisms of
      acquired endocrine resistance, offering exciting prospects for extending the
      impact of successful sequential endocrine therapies; presentation of high-quality
      evidence indicating that chemotherapy and tamoxifen should be used sequentially
      rather than concurrently; availability of a potential alternative to tamoxifen
      for treatment of postmenopausal women with endocrine responsive disease; promise
      of newly defined prognostic and predictive markers.

PMID- 14659137
TI  - Hormonal therapy: introduction.

PMID- 14659138
TI  - Challenges in the endocrine management of breast cancer.
AB  - The goal of endocrine therapy in breast cancer is to block the action of estrogen
      on the tumor cells either by inhibiting estrogen from binding to the specific
      estrogen receptor or by inhibiting its synthesis. Tamoxifen, a selective estrogen
      receptor modulator, is the standard endocrine treatment for hormone receptor
      positive breast cancer, both in the adjuvant and metastatic settings. Tamoxifen
      inhibits the binding of estrogen to the receptor, resulting in inhibition of
      hormone action. However, as tamoxifen is also weakly estrogenic, it may not be
      optimally effective and increases the risk of endometrial cancer and stroke.
      Furthermore, patients may be refractory or may become resistant to tamoxifen
      treatment. Since aromatase inhibitors (AI) block the synthesis of estrogen and
      have no intrinsic estrogenic activity, they have the potential to be more
      effective than tamoxifen. Their different mechanism of action and chemical
      structures may also circumvent tamoxifen resistance. Consequently, AIs are
      currently being evaluated as an alternative to tamoxifen treatment. A preclinical
      model has recently been developed to compare the efficacy of AIs and
      antiestrogens in different treatment schemes and to assist in the design of
      clinical trials. Current studies with the MCF-7Ca xenograft model are exploring
      the effects of combination and sequential therapy on tumor growth. The efficacy
      of AIs in the treatment of hormone receptor-positive breast cancer was first
      demonstrated in five multicenter second-line trials enrolling several hundreds of
      postmenopausal patients with metastatic breast cancer who had failed tamoxifen
      treatment. More recently, anastrozole demonstrated efficacy at least equivalent
      to that of tamoxifen in first-line randomized, phase III clinical trials in
      postmenopausal women with hormone receptor-positive or unknown metastatic breast
      cancer, whereas letrozole demonstrated superiority. The steroidal AI exemestane
      is currently under evaluation. Letrozole is the only AI to have been studied in a
      randomized, phase III trial in the neoadjuvant setting. In this trial, more
      patients underwent breast-conserving surgery with letrozole than with tamoxifen.
      Smaller phase II studies also suggest that both anastrozole and exemestane are
      active in the neoadjuvant setting. Because neoadjuvant trials permit temporal
      sampling of breast tissue, substudies in the phase III trial with letrozole have
      examined the impact of such biomarkers as estrogen receptor, progesterone
      receptor and epidermal growth factor receptor family members, HER-1 and HER-2, on
      patient response. AIs are currently under evaluation in the adjuvant setting, and
      preliminary results of the Arimidex, Tamoxifen Alone or in Combination (ATAC)
      trial have been reported. AIs have proven as safe as tamoxifen in trials in
      patients with metastatic breast cancer. Ongoing clinical trials in the adjuvant
      setting include companion studies of end-organ effects, particularly bone
      metabolism and lipid metabolism evaluations. Quality-of-life assessments are also
      parts of major clinical trials. A head-to-head quality-of-life assessment of
      anastrozole compared with letrozole demonstrated patient preference for
      letrozole. These assessments also clearly indicated the eagerness of patients to
      participate actively in treatment decisions

PMID- 14659139
TI  - Role of bisphosphonate therapy in breast cancer and other advanced malignancies.

PMID- 14659140
TI  - Proven efficacy of zoledronic acid in the treatment of bone metastases in
      patients with breast cancer and other malignancies.
AB  - Many advanced cancers, particularly breast cancer and prostate cancer,
      metastasize to the bone, resulting in painful lesions and skeletal complications.
      Intravenous bisphosphonate therapy is an important component of palliative care
      for patients with bone metastases, and pamidronate has been the standard of care
      for patients with breast cancer and multiple myeloma since 1996. However,
      zoledronic acid is the first bisphosphonate shown to significantly reduce
      skeletal morbidity in patients with a wide range of primary tumor types.
      Zoledronic acid has demonstrated efficacy in the management of hypercalcemia and
      metastatic bone disease. In phase III studies involving more than 3000 patients
      with multiple myeloma, breast cancer, prostate cancer, lung cancer, and other
      cancers, 4 mg zoledronic acid demonstrated consistent efficacy across a range of
      clinical end-points, and was safe and well tolerated when infused over 15 min.
      Based on these studies, zoledronic acid appears to be active in patients with
      bone metastases irrespective of tumor type, and should be considered as the
      standard of care for the treatment of bone metastases.

PMID- 14659141
TI  - The anti-tumor potential of zoledronic acid.
AB  - Bone is a favorable microenvironment for tumor cell colonization because of
      abundant growth factors released during active bone resorption. Bisphosphonates
      can dramatically affect the ability of tumor cells to grow in bone by inhibiting
      osteoclast-mediated bone resorption and by depriving tumors of growth-promoting
      signals. Moreover, bisphosphonates have direct anti-tumor effects in vitro via
      induction of apoptosis. Zoledronic acid is a nitrogen-containing bisphosphonate
      that has demonstrated potent anti-tumor activity in vitro and in vivo. In vitro
      studies have provided important clues as to the molecular mechanisms by which
      zoledronic acid induces apoptosis of human breast cancer cell lines. Studies in
      multiple myeloma and breast cancer models have shed further light on the possible
      mechanisms underlying the in vivo anti-tumor effects of zoledronic acid. These
      studies have led to the development of novel strategies to target specific
      molecular pathways involved in osteoclast maturation and activity, tumor cell
      metastasis, and tumor growth and survival. The clinical application of these
      strategies may ultimately prevent bone metastasis.

PMID- 14659142
TI  - Rationale for the use of bisphosphonates in osteoblastic and osteolytic bone
      lesions.
AB  - Various primary malignancies develop bone metastases, and the resultant skeletal
      complications cause significant morbidity/mortality in advanced cancer patients.
      Bone lesions associated with metastases are traditionally classified
      radiologically as either osteolytic or osteoblastic, and both types of lesions
      are associated with elevated levels of specific bone resorption markers. Some
      common aspects in the pathophysiology of bone lesions have prompted speculation
      that treatments for osteolytic metastases might also be effective for
      predominantly osteoblastic metastases, such as in prostate cancer. Potent
      osteoclast activity inhibitors, bisphosphonates have been successful in the
      treatment of osteolytic tumor bone disease. Zoledronic acid is the first
      bisphosphonate shown to have a direct clinical benefit in the treatment of
      osteoblastic bone metastases, reducing the number and rate of skeletal events in
      prostate cancer patients with metastatic bone disease. Moreover, the shorter,
      more convenient infusion time and similar safety profile of 4 mg zoledronic acid
      compared with 90 mg pamidronate presently make zoledronic acid the preferred
      therapy for treatment of bone metastases in patients with all types of advanced
      malignancy.

PMID- 14659143
TI  - Why improvement in survival of screen-detected cases is not necessarily
      equivalent to benefit?

PMID- 14659144
TI  - Systematic review of fibroadenoma as a risk factor for breast cancer.
AB  - Fibroadenoma (FA) is a common breast lesion occurring in 25% of asymptomatic
      women. Several studies considered FA as a risk factor for breast cancer,
      prompting a systematic review of the literature. We selected cohort and case
      control studies. Seven studies satisfied the selection criteria. Dupont et al.
      (1994) and McDivitt et al. (1992) were considered to provide the strongest
      evidence, showing the relative risk for excised FA without hyperplasia in the
      range 1.48-1.7, with hyperplasia 3.47-3.7, and with hyperplasia and atypia 6.9
      7.29, persisting for more than 20 years. Five studies by Levi et al. (1994),
      Ciatto et al. (1997), Moskowitz et al. (1980), Carter et al. (1988), and Levshin
      et al. (1998), were considered to provide weaker evidence, although they showed
      similar results. None of the results could be used to quantify the risks of
      excised, non-excised, and asymptomatic FA. More care should be taken in managing
      patients with complex FAs and FAs with hyperplasia with or without atypia. Core
      biopsy may be a better option in diagnosis of FAs. Regular screening may be
      advisable in patients with FAs and a family history of breast cancer in a first
      degree relative. More rigorous research is needed in this area.

PMID- 14659145
TI  - Significant improvement in breast cancer survival through population-based
      mammography screening.
AB  - The purpose of this study was to evaluate the effect of population-based
      mammography screening on survival. A total of 176 908 screening examinations were
      performed in 36 000 women aged 40-74 during the years 1987-1997. Screen-detected
      and interval primary invasive breast cancers (n=685, screened) were more often
      smaller (P<0.0001), localised (P<0.0001) and histologically better differentiated
      (grade I vs II-III, P<0.0001) than pre-screening cancers and cancers detected
      after the defined interval from the last screening (n=184, clinical). Survival
      was far better in the "screened" group than in the "clinical" group (P<0.0001, HR
      2.55; CI 95% 1.77-3.67). Cox's multivariate analysis revealed axillary lymph node
      negativity (P<0.0001), histological grade I (P=0.0005) and size less than or
      equal to 20mm (P=0.0118) as explanations of the beneficial effect of screening. A
      new observation we recorded was that screening had a beneficial effect even in
      women whose cancer had already spread into the axillary lymph nodes.

PMID- 14659146
TI  - Fine-needle aspiration cytology in nonpalpable mammographic abnormalities in
      breast cancer screening: results from the breast cancer screening programme in
      Oslo 1996-2001.
AB  - Fine-needle aspiration cytology (FNAC) of nonpalpable mammographic lesions has
      been under attack from two sides for some years. There has been much discussion
      and controversy as to the ability to differentiate between in situ and invasive
      carcinomas in cytological material. A further issue is that of optimal sampling
      to obtain adequate cell material in sufficient quantity. We present the results
      of FNAC from 832 nonpalpable mammographic abnormalities detected in the course of
      the breast cancer screening programme in Oslo during 1996-2001. In 11.6% of cases
      the smears were inadequate, and there were 7% false negatives (FN) and 1.3% false
      positives. Of the FN, 64% represented microcalcifications and 86% were due to
      sampling errors. Absolute sensitivity was 74%, complete sensitivity 88% and
      specificity 88%. In 255 carcinomas a cytological diagnosis of them as in situ or
      invasive was made. In 93% of the invasive cases (190/205) these had been
      correctly identified as invasive on FNAC. In 78% of cases proper follow-up could
      be resolved by cytology/radiology alone. Suboptimal sampling and localization
      remains the main cause of FN FNAC results. Problems in differentiating between in
      situ and invasive breast carcinomas can be significantly reduced by applying
      strict criteria for in situ lesions.

PMID- 14659147
TI  - A new histological grading system to assess response of breast cancers to primary
      chemotherapy: prognostic significance and survival.
AB  - The clinical and complete pathological response of a primary breast cancer to
      chemotherapy has been shown to be an important prognostic for survival. However,
      the majority of patients do not experience a complete pathological response to
      primary chemotherapy and the significance of lesser degrees of histological
      response is uncertain and the prognostic significance is unknown. The purpose of
      this study was to evaluate a new histological grading system to assess response
      of breast cancers to primary chemotherapy and to determine if such a system has
      prognostic value.A consecutive series of 176 patients with large (> or =4cm) and
      locally advanced breast cancers were treated with multimodality therapy
      comprising primary chemotherapy, surgery, radiotherapy and tamoxifen. All
      underwent assessment of the primary breast tumour before and after completion of
      chemotherapy. Residual tumour was excised after completion of chemotherapy
      (mastectomy or wide local excision with axillary surgery). The removed tissue was
      assessed and response to chemotherapy graded using a five-point histological
      grading system based with the fundamental feature being a reduction in tumour
      cellularity; comparison being made with a pre-treatment core biopsy. All patients
      were followed up for 5 years or more. Pathological responses were compared to 5
      year overall survival and disease-free survival using log rank tests. The overall
      5-year survival for all patients was 71%, and 5 year disease free interval was
      60%. There was a significant correlation between pathological response using this
      new grading system and both overall survival (P=0.02) and disease-free interval
      (P=0.04). In a multivariate analysis of known prognostic factors, the
      Miller/Payne grading system was an independent predictor of overall patient
      survival. This grading system, which assesses the histological response to
      primary chemotherapy, can predict overall survival and disease-free interval in
      patients with large and locally advanced breast cancers treated with such
      therapy. The relationship of degree of histological response to overall and
      disease-free survival has been shown in univariate and multivariate analyses and
      could potentially have an important role in the clinical management of patients
      with locally advanced breast cancer undergoing primary chemotherapy.

PMID- 14659148
TI  - Management of recurrent locoregional breast cancer: oncologist survey.
AB  - Locoregional recurrence (LRR) after therapy for early breast cancer is common. A
      questionnaire was used to assess consensus between breast oncologists about the
      definition, prognosis and management of patients with LRR. The questionnaire was
      mailed to surgical, radiation and medical oncologists in Canada, the UK and the
      USA. Of 495 questionnaires, 322 (65%) were returned. Most clinicians sampled
      agree that disease in the skin of the chest wall, surgical scar, axilla,
      ipsilateral breast tumor recurrence (IBTR), infraclavicular lymph nodes,
      supraclavicular fossa lymph nodes and internal mammary lymph nodes constitute
      sites of LRR. The sites that were felt to be curable by the majority of
      respondents were: IBTR, surgical scar, axilla or chest wall. It was for these
      disease sites that local therapy was generally recommended. Irrespective of the
      site of recurrence, most respondents surveyed recommend initiation of a new
      systemic therapy at the time of LRR. While the results of this survey show
      general agreement regarding the definition of sites of LRR, treatment
      recommendations vary among oncologists. Due to the variation in sites of
      recurrence, time since initial diagnosis and prior therapy, the exact prognosis
      and optimal management of LRR remain undefined. In the absence of randomized
      prospective trial data, recommendations for local and systemic therapy of LRR
      will continue to mimic those offered at the time of initial presentation of
      breast cancer.

PMID- 14659149
TI  - Mastectomy using ultrasonic dissection: effect on seroma formation.
AB  - Seroma formation is the most common complication after mastectomy. Among the
      several known etiological factors the surgical procedure used may be of
      importance for seroma formation. This prospective study was carried out to
      evaluate the ultrasonic energy dissection technique and its effect on seroma
      formation and other complications: 59 patients with operable breast cancer
      underwent modified radical mastectomy, performed in 30 of them with an
      Ultracision Harmonic scalpel and in 29 with scissors and electrocautery. In all
      cases a standard level II axillary dissection was performed with scissors. We
      found no differences in the outcome of surgery. Peroperative bleeding (median 300
      ml, range 100-790 vs 300 ml, range 40-1400), drain volume (585 ml, range 130
      1455) vs 645 ml, range 95-1570), seroma formation 50 (0-580) ml vs 105 (0-3775)
      ml and wound complications were about the same in both groups. In conclusion,
      neither clinical advantages or disadvantages of the ultrasound dissection
      technique were found.

PMID- 14659150
TI  - Cutaneous ectopic breast calcification in a haemodialysis patient.
AB  - This case report details the unique breast calcification and swellings of a 61
      year-old lady. The ectopic breast calcification was a result of chronic renal
      failure and hyperparathyroidism secondary to vesiculo-ureteric reflux
      nephropathy. Subcutaneous nodules were also noted around her ileostomy (from
      surgery due to Crohn's disease) and abdominal wall. Mammogram revealed calcified
      breast discs and lobules with extensive vascular calcification. Histological
      biopsies revealed extensive calcium deposition (benign). Cutaneous deposition of
      calcium oxalate has been described in 13 patients world wide, usually involving
      fingers, ears, or nose. Two of these report breast involvement, but this is
      described as less extensive and more focal calcification on clinical findings and
      mammography. This case report describes a rare condition with extraordinary
      mammographic images.

PMID- 14659151
TI  - Report of a male patient with brain metastases from breast cancer.
AB  - As in female patients, the clinical course in male patients with breast cancer is
      determined mainly by tumor stage. The literature contains very limited data on
      either the occurrence or the treatment of CNS metastases. This paper presents the
      case report of a 69-year-old man with multiple brain metastases 7 years after a
      diagnosis of lymph-node positive breast cancer, which had earlier already spread
      to the bones and liver. Whole-brain irradiation with a total dose of 30Gy
      resulted in palliation of symptoms. Nevertheless, survival was very short (7
      weeks from diagnosis). Patients with metastatic breast cancer are at risk for the
      development of brain metastases. When performance status is poor the survival of
      patients with brain metastases is very limited. Treatment recommendations are the
      same as those for female patients with brain metastases from breast cancer.

PMID- 14659152
TI  - Primary Therapy of Early Breast Cancer. Abstracts of the 8th International
      Conference. March 12-15, 2003. St Gallen, Switzerland.

PMID- 14659307
TI  - Socioeconomic status & returning for a second screen in the Ontario breast
      screening program.
AB  - In a retrospective cohort study involving 57902 women initially screened between
      January 1, 1995 and December 31 1997 by the Ontario Breast Screening Program
      (OBSP), we examined the relationship between geographically derived socioeconomic
      status (SES) and returning for a second screen. We controlled for age, rurality,
      preferred language, initial mammography results, previous mammography history,
      and referral by a health professional. Although SES was related to returning,
      rurality was an effect modifier of this relationship, a finding not previously
      reported. Compared to women in the highest ('richest') quintile, urban women in
      the first and second quintile were less likely to return; this relationship was
      not found in rural women. Low SES women, particularly in urban areas, should be
      specifically targeted to increase their likelihood of re-attendance for breast
      cancer screening within an organized program.

PMID- 14659308
TI  - Breast cancer in young women: clinicopathological features and biological
      specificity.
AB  - Literature data suggest that breast cancers occurring in young patients may be
      different from those arising in older women. In this study the clinicopathologic
      characteristics of 50 patients under 40 years of age were compared with those of
      patients aged over 60. Patients under 40 years old more frequently had a family
      history of breast cancer than did older patients (24% vs 17%) and had more often
      used oral contraceptives (29% vs 13%); on average they had experienced menarche 1
      year earlier. For early onset breast carcinomas there was a higher frequency of
      grade 3 tumours (38% vs 17%) and oestrogen receptor negativity (46% vs 20%). In
      addition, in younger patients the carcinomas were mostly DNA aneuploid (78% vs
      58%), with a higher proliferation rate (48% vs 26%) and more frequent c-erbB-2
      overexpression (48% vs 26%) and p53 alteration (30% vs 8%). Our data demonstrate
      that breast cancers arising in young women have a significantly different
      biopathological profile from those in older patients, with a predominance of
      unfavourable prognostic parameters.

PMID- 14659309
TI  - Neuroendocrine differentiated carcinomas of the breast: a distinct entity.
AB  - Some primary carcinomas of the breast have been classified as neuroendocrine. In
      this paper we report on 12 cases of neuroendocrine carcinoma of the breast
      displaying common and uncommon histological features. MATERIALS AND METHODS: All
      patients were aged from 43 to 79 (median 66.5) years. The tumors were unilateral
      and ranged from 0.8 to 7 cm (median 2.35 cm) in diameter. Four tumors were
      classified as solid cohesive, two as solid papillary, one as Merkel cell-like,
      two as cellular mucinous, two as cellular mucinous with micropapillary features
      and one as cellular mucinous with prominent signet ring cells. The tissues were
      fixed in formalin and routinely processed. All materials were stained with PAS,
      Alcian blue and also hematoxylin and eosin. Immunohistochemical examination was
      carried out by the avidin-biotin method using the following antibodies: estrogen
      receptor protein, progesterone receptor protein, p53, cerbB-2, Ki67, neuron
      specific enolase, chromogranin, and synaptophysin. RESULTS: In all cases the
      tumor cells were stained positively with NSE. Synaptophysin and chromogranin
      positivity was detected in 11 and five cases, respectively. The prominent
      histological features were: extensive intraductal growth, pseudorosettes and
      palisades, low-grade cytologic atypia, plasmacytoid appearance of the tumor
      cells, and intracellular and extracellular mucin. CONCLUSION: Neuroendocrine
      differentiated carcinoma of the breast is a rare and distinct category with
      different histological subtypes.

PMID- 14659310
TI  - Palpable breast lesions: utility of Doppler sonography for diagnosis of
      malignancy.
AB  - This study was designed to find whether there are any differences between benign
      and malignant palpable breast lesions as they are seen on grey-scale and colour
      Doppler and on power-Doppler sonography; to determine which variables for each
      technique are most helpful in distinguishing any such differences; and to see
      whether the use of an echo-enhancing agent gives better results in the
      differential diagnosis. Forty-five palpable breast lesions (16 benign and 29
      malignant) were evaluated in a preoperative study using grey-scale sonography,
      colour-Doppler sonography and power-Doppler sonography before and after
      administration of an echo-enhancing agent (Levovist). We reached the following
      conclusions: (1) In the grey-scale ultrasound study of palpable breast lesions
      the presence of microcalcifications, acoustic shadowing and non-well-defined
      margins are related to malignancy. (2) Colour- and power-Doppler sonography may
      help in the differential diagnosis. (3) The use of an echo enhancer (Levovist)
      accentuates these differences and enables them to be noted in other variables,
      such as pulsatility index, nodule-to-vascularity ratio and number of poles.

PMID- 14659311
TI  - Carbon localisation of impalpable breast lesions.
AB  - BACKGROUND: Hookwire localisation (HL) is the most widely used technique for
      excision of impalpable breast lesions. This method has several drawbacks,
      particularly with logistics. Carbon localisation (CL) is an alternative procedure
      which is logistically superior to HL, but comparisons of accuracy and costs have
      not been reported. METHODS: A consecutive case series of all patients from
      Northwestern BreastScreen undergoing either CL or HL between January 1999 and
      March 2001. FINDINGS: Of 511 procedures, 219 CLs and 292 HLs were performed. The
      accuracy of excision did not vary significantly. Where a preoperative diagnosis
      of malignancy had been made by percutaneous needle biopsy (PNB), the margins were
      <1mm in 27 of the CL group (18.9%) and 21 of the HL group (29.2%) (P=0.087). Cost
      analysis was very favourable for CL performed concurrently with PNB since the
      costs were incremental. INTERPRETATION: At service delivery level, CL is an
      accurate alternative to HL with better logistics and favourable costs.
      Nationally, it has the potential to improve the cost effectiveness of breast
      screening programmes.

PMID- 14659312
TI  - The contribution of work-up or additional views to the accuracy of diagnostic
      mammography.
AB  - This study examines the influence of work-up on the accuracy of diagnostic
      mammography in symptomatic women. Subjects were sampled from all women
      consecutively attending a symptomatic breast clinic and aged 25-55 years (240
      women shown to have breast cancer and 240 age-matched women shown not to have
      cancer). Mammography films were prospectively reported by two radiologists
      independently of each other and in a blinded manner using two phases of film
      reading: initially only baseline films were read, then mammography was re-read
      with work-up films. The accuracy of reporting mammography with and without work
      up was compared using sensitivity and specificity, likelihood ratios, and
      receiver operating characteristic (ROC) curves. Reporting the mammogram with work
      up (compared to without any work-up films) improved sensitivity (75.3% vs 69.0%,
      P=0.059) for one radiologist, with a non-significant gain in specificity (84.5%
      vs 79.4%, P=0.38). For the other radiologist, it resulted in a non-significant
      decrease in sensitivity (79.5% vs 83.7%, P=0.14) with a significant increase in
      specificity (85.6% vs 61.9%, P=0.00001). ROC curves for both radiologists showed
      that reporting mammography with work-up resulted in significant improvement (4.5%
      for R1, 6.8% for R2) in overall test accuracy. Our findings support the use of
      work-up mammography in the diagnostic setting.

PMID- 14659313
TI  - Final diagnoses following C3 (atypical, probably benign) breast cytology.
AB  - Fine needle aspiration cytology is part of the triple assessment of breast
      lesions. The final diagnoses are reported in patients with breast lesions that
      produce C3 or atypical, probably benign cytology. C3 cytology was obtained from
      61 breast lesions between January 1998 and December 1999. Ten (16%) of these
      lesions were malignant, only three of which were clinically or radiologically
      suspicious or malignant. Three were diagnosed by core biopsy, but three required
      excision biopsy after a benign core, and four diagnosed by excision without core.
      For benign lesions; in five the core was considered diagnostic, three were
      excised to confirm benignity, 11 monitored and 32 excised without core. Core
      biopsy should be performed in preference to cytology in the assessment of breast
      lesions. Where C3 cytology is obtained, core biopsy should be performed, but
      excision biopsy may still be required. The definition of C3 cytology should be
      changed to indeterminate.

PMID- 14659314
TI  - Are dopamine antagonists a risk factor for breast cancer? An answer from
      Parkinson's disease.
AB  - Women undergoing chemotherapy for breast cancer are often administered dopamine
      antagonist adjuvant medications that may increase levels of prolactin potentially
      increasing the risk of cancer. Using nationwide computerized registers of death
      data for the years 1991 through 1996 we examined 12,430,473 deaths of persons
      over 40 years of age and extracted 144,364 cases with Parkinson's disease (PD), a
      dopamine deficient population. Patients with PD had lower rates of breast and
      other types of malignancies, even in the presence of depression and suicide.

PMID- 14659315
TI  - Granulomatous mastitis can mimic breast cancer on clinical, radiological or
      cytological examination: a cautionary tale.
AB  - In both women and men, breast lumps are the most common presentation of breast
      cancer. The following cases illustrate the pathological entity of granulomatous
      mastitis, which can present simulating breast cancer - including the first
      description of this condition in a male. These cases demonstrate the difficulty
      in clinical diagnosis and emphasizes that although there may be clues from the
      history, clinical awareness that this condition can mimic breast cancer in all
      aspects of the triple assessment process should arouse suspicion. The importance
      of histological diagnosis by core or excision biopsy is stressed, as with
      accurate diagnosis of granulomatous mastitis there is a mandate to avoid
      unnecessary surgery.

PMID- 14659316
TI  - Catheter fracture: a rare complication of totally implantable venous devices.
AB  - The use of totally implantable venous devices (TIVDs) has revolutionised the care
      and quality of life of oncology patients. Although considered to be generally
      safe, catheter fracture is a rare but serious complication. The 'pinch-off'
      syndrome is caused by the compression of the catheter between the clavicle and
      first rib, and may lead to fracture and possible dislocation of the catheter. We
      report here the case history of two patients with metastatic breast cancer who
      developed the 'pinch-off' syndrome, first recognised by difficulty in line
      aspiration and pain during injection of the catheter. In one case, there was
      complete fracture with migration of the catheter tip to the right pulmonary
      artery. In both cases, the lines were removed without serious injury to the
      patient. All patients with TIVDs should be investigated for possible catheter
      fracture if they develop pain over the superior anterior chest wall and/or there
      is difficulty or pain during aspiration or injection.

PMID- 14659317
TI  - Breast cancer after bilateral subcutaneous mastectomy in a female-to-male trans
      sexual.
AB  - We describe a female-to-male trans-sexual, aged 33, who developed breast cancer
      10 years after cosmetic bilateral subcutaneous mastectomy and nipple
      reimplantation. The complex hormonal pathways involved and the implications for
      women undergoing prophylactic mastectomy because of a high risk of familial
      breast cancer are discussed.

PMID- 14659318
TI  - Multiple metastatic deposits of a left breast cancer into a right fibroadenoma.
AB  - We present a case which we believe to be the first report of carcinoma of the
      breast metastasising into a long-standing fibroadenoma in the contralateral
      breast.

PMID- 14659320
TI  - Is it time for a paradigm shift in the training of breast surgeons as a sub
      speciality?!

PMID- 14659321
TI  - The future of breast surgery: a new subspecialty of oncoplastic breast surgeons?

PMID- 14659322
TI  - Current controversies in sentinel lymph node biopsy for breast cancer.
AB  - Despite the widespread use of sentinel lymph node biopsy (SLNBx) in the surgical
      management of breast cancer patients, several areas remain controversial. The
      following controversies are reviewed: Learning curves and validation studies.
      There clearly is a learning curve, and a completion ALND should be done until
      adequate proficiency is exhibited, both in terms of identification and false
      negative rates. Location of injection. Intradermal injection offers superior
      identification rates compared with peritumoral injection, with comparable false
      negative rates. Subareolar injection is as accurate as peritumoral injection. The
      value of scintigraphy. Routine scintigraphy does not enhance identification or
      false-negative rates. Mapping agents. Blue dye and radioactive tracer combined to
      provide a higher identification rate than either used alone.SLNBx in DCIS. In
      patients with a high risk of microinvasion, such as large tumors, a mass or high
      grade DCIS-SLNBx is justified.SLNBx following neoadjuvant chemotherapy. Although
      there is evidence that SLNBx after neoadjuvant chemotherapy may be accurate,
      these data should be applied cautiously. Implications of non axillary SLN,
      especially internal mammary nodes. Data do not support routine resection of
      internal mammary sentinel lymph nodes outside a clinical trial. Implications of
      micrometastases in the sentinel lymph node seen only on immunohistochemistry.
      Since the significance of such metastases is unclear, decisions regarding
      treatment of these patients should be individualized. The value of completion
      axillary lymph node dissection. Is being addressed in clinical trials. Until
      those studies mature, completion ALND should be performed for patients with SLN
      metastases, but may be abandoned for patients with a negative SLN.

PMID- 14659323
TI  - Immunohistochemical evaluation of immune response in invasive ductal breast
      cancer of not-otherwise-specified type.
AB  - We investigated endotumoral and peritumoral lymphocytic subsets [natural killer
      cells (NK), B-cells and cytotoxic/suppressor (CD(8)+) T-cells], and expression of
      MUC1 and MUC6 glycoprotein with regard to various clinicopathological parameters
      in invasive breast cancer tissues. The study population consisted of 64 female
      patients with invasive ductal breast cancer of not-otherwise-specified type.
      Thirty-five women with benign breast lesions served as controls. High-grade
      carcinomas exhibited higher numbers of endotumoral NK cells and B-cell aggregates
      than the rest of the tumors examined (P=0.0003 and 0.027, respectively). Cases
      with more than three positive lymph nodes and with tumors over 2 cm in diameter
      exhibited higher numbers of endotumoral NK cells (P=0.047 and 0.023,
      respectively). Increased numbers of peritumoral CD(8)+ T-cells were detected in
      cases with lymph node metastases (P=0.045). MUC1 was expressed with weaker
      staining intensity in the control group than in the group with breast cancer
      (P=0.011). Grade III carcinomas exhibited significantly stronger expression of
      MUC6 glycoprotein (P=0.001) than the control group. In conclusion, tumors with
      markers of poor prognosis exhibited increased numbers of lymphocytic infiltrates,
      and of NK cells in particular, and stronger MUC1 and MUC6 glycoprotein
      immunoreactivity than did the other tumors.

PMID- 14659324
TI  - In vivo 1H-MRS evaluation of malignant and benign breast diseases.
AB  - This study was purposed to evaluate malignant and benign breast diseases on the
      basis of detecting choline compounds by in vivo localized 1H-MR spectroscopy.
      Thirty-five patients, prior to surgical treatments, including 19 cancers and 16
      benign diseases were examined with breast imaging coil and inversion recovery 1H
      PRESS (TR/TE/TI: 2000 ms/288 ms/160 ms) MR spectroscopy. Detection of choline was
      compared with the results of biopsy in each case. Choline was observed in all 19
      cancer patients, while it was not detected in all other benign diseases.
      Detecting sensitivity of choline widely varied over the cancer cases in the range
      of 2.4-12.7 (average SNR value of 5.4) depending on the water/fat suppression and
      voxel size. Localized 1H-MRS using breast imaging coil can provide excellent
      sensitivity and spectral resolution to detect choline compounds present in
      reasonably small voxel (<1.5 cm3) of breast cancer lesion. Substantially this
      finding would be useful for differential diagnosis between malignant and benign
      breast diseases on the basis of choline observation by 1H-MRS when combined use
      with MR imaging.

PMID- 14659325
TI  - Service screening with mammography. Long-term effects on breast cancer mortality
      in the county of Gavleborg, Sweden.
AB  - In the current study the long-term effects of a pilot service screening programme
      in the Swedish county of Gavleborg were studied. Women aged 40-64 years in 13 sub
      areas were followed from start of screening between 1974 and 1979. Two control
      groups were used for comparison; the neighbouring counties and all of Sweden. A
      reference period prior to the study period was used to facilitate an adjustment
      for possible differences in baseline breast cancer mortality. Only deaths from
      breast cancer diagnosed after the first invitation to screening were analysed.
      Two outcome measures were used for breast cancer mortality; the underlying cause
      of death and excess mortality. Using the neighbouring counties as a control
      group, the relative risk, after 22 years of follow-up, of 10 years of screening
      was estimated at 0.84 (95% CI 0.71-1.00) using excess mortality. Due to lead time
      bias the relative risk was overestimated by 4%. Hence, a significant 20%
      reduction of breast cancer excess mortality was found.

PMID- 14659326
TI  - Sentinel lymph node imaging and research after bone scintigraphy in breast cancer
      patients.
AB  - The aim of the study is to see if Bone Scan (BS) - when performed the day before
      the operation-interferes with the results of the Sentinel Lymph Node (SLN)
      technique using radiocolloids (their pre-operative imaging and their peroperative
      research). Therefore, the data of 393 patients who had one selective
      lymphadenectomy of the SLN(s) followed by the complete axillary node (AxN)
      clearance for Breast Cancer and among whom 309 patients had one BS the day before
      the operation (and just before the injection-s for the SLN) and 84 did not, were
      analysed and compared. The two series presented the same characteristics with
      regard to: age, clinical staging of the tumour, kind of injection-s performed
      (intradermic and paratumoural and/or intraparenchymal and peritumoral),
      pathological size of the tumour, percentage of cases with no AxN invasion, total
      number of AxN removed by the surgeons. The percentages of no axillary SLN
      visualisation, the mean numbers of axillary SLN visualised on pre-operative
      lymphoscintigram as well as of SLN removed by the surgeons were not statistically
      different in the groups of patients with (respectively, 12.11, 2.6 and 3.03) and
      without BS (respectively, 12.99, 2.7 and 2.96). More noteworthy, the false
      negative (FN) rate of the SLN technique, albeit having a higher observed value in
      the group with BS (9.6%, 12/125), did not differ significantly from that in the
      group without BS (5.6%, 2/36). The accuracies (overall correct classification
      rates), the sensitivities and the negative predictive values of the SLN technique
      also did not differ significantly between the two groups. It is concluded that
      the SLN technique can be accurately performed just after one BS.

PMID- 14659327
TI  - Paraneoplastic neurological disorders in breast cancer.
AB  - Paraneoplastic syndromes are the rarest neurological complications in patients
      with cancer. The neurological paraneoplastic syndromes that are mainly associated
      with breast cancer are subacute cerebellar degeneration, paraneoplastic
      retinopathy, opsoclonus-myoclonus syndrome, lower motor neuron diseases and Stiff
      man syndrome. The aim of this paper is to briefly outline these paraneoplastic
      neurological syndromes and consider their relation to breast carcinoma.

PMID- 14659328
TI  - Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes:
      vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up
      by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide
      sequential followed up by paclitaxel. A phase II study.
AB  - PURPOSE: The efficacy of anthracyclin-containing adjuvant chemotherapy of node
      positive breast cancer can be further improved by adding sequential paclitaxel
      (T). There is also clinical evidence that replacing cyclophosphamide (C) with
      vinorelbin (V) might further reduce toxicity. In order to assess the safety of
      these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide
      and epirubicin/vinorelbine with or without sequential paclitaxel. METHOD:
      Patients with node-positive (1-3) breast cancer were assigned to open-label
      epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel
      (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus
      sequential paclitaxel (EC/T) therapy. RESULTS: Fifty four outpatients received a
      total of 304 chemotherapy cycles. There were significant differences in grade
      III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group
      (P=0.002). CONCLUSIONS: The safety of paclitaxel is not impaired when given
      sequentially after administration of the two anthracyclin-containing regimens.
      The exchange of cyclophosphamide against vinorelbine leads to deteriorating
      safety of the EC/T regimen.

PMID- 14659329
TI  - MR mammography of a primary squamous cell carcinoma of the breast: a case report.
AB  - A case of a primary squamous cell carcinoma of the breast in a patient with
      synchronous contralateral invasive ductal adenocarcinoma is reported. To our
      knowledge, no dynamic MR mammography of this pathology is described in the
      literature. On MR, it presented as a mainly non-enhancing, partially cystic mass
      with an enhancing irregular peripheral rim. In the differential diagnosis of a
      mass with unsharp margins and an irregular border of the cystic or the non
      enhancing area on MR mammography, a primary squamous cell carcinoma must be
      included.

PMID- 14659330
TI  - Cerebrospinal fluid pseudocyst of the breast.
AB  - A 39 year old lady presented with a lump in her right breast. She was known to
      have had a ventriculo-peritoneal shunt inserted for childhood hydrocephalus.
      Mammography revealed a calcified, fractured shunt with an associated soft tissue
      swelling which resolved following shunt removal. Shunt fracture secondary to
      calcification is extremely rare, and presentation as a breast lump has not been
      previously described. This case identifies a rare cause of breast lumps and
      highlights the importance of complete triple assessment in all patients
      presenting with a breast lump.

PMID- 14659331
TI  - Bilateral breast cancer associated with diffuse scleroderma.
AB  - There is a strong evidence to suggest the association between breast cancer and
      diffuse scleroderma, though it is an infrequent occurrence. We describe the
      clinical and radiological findings in a patient who, over a period of 2 years,
      was diagnosed initially of diffuse scleroderma, next with right breast cancer and
      finally with left breast cancer. A review of the literature evidencing the
      relation between these two pathologies is provided. We suggest that special
      vigilance for tumoral pathology of the breast should be performed in patients
      with systemic scleroderma.

PMID- 14659332
TI  - An unusual case of an enlarging mass on a screening mammogram: a case report and
      review of the radiology and current literature.
AB  - We report the case of a woman who was recalled after screening because an opacity
      seen on her previous screening mammogram had changed in appearance. The new
      features were of a circumscribed soft-tissue opacity with some lobulation.
      Ultrasound showed an oval mass which was slightly hypoechoic compared to the
      surrounding fatty parenchyma and contained small focal anechoic areas. The lesion
      was biopsied and found to be a cavernous haemangioma. Haemangioma of the breast
      is a rare cause of a well-circumscribed soft-tissue mass on a mammogram.

PMID- 14659333
TI  - New technologies for diagnosis and treatment of breast cancer: meeting highlights
      from the Fourth Milan Breast Cancer Conference (Milan, June 5-7, 2002).

PMID- 14659335
TI  - Synchronous, bilateral breast cancer: prognostic value and incidence.
AB  - The purpose of this study was to address the question whether patients with
      bilateral breast cancer (BBC) have a worse prognosis in terms of recurrence and
      survival than patients with primarily unilateral breast cancer (UBC) following
      breast-conserving treatment (BCT). From 1983 to 2000, a total of 1760 BCT were
      registered in the Radiotherapy Department of the Medisch Spectrum Twente. We
      defined synchronous a BBC as cancer diagnosed in both breasts at the same time or
      within a period of 3 months of diagnosis of the first tumor. One thousand seven
      hundred and sixty BCT were performed on 1705 patients, 26 of whom presented with
      BBC. Of these 26 patients, 18 had BCT for both breasts. A higher proportion of
      patients with BBC showed more tubular carcinoma (P=0.029) and medially located
      tumors (P=0.076) than those with UBC did. The 5- and 10-year local recurrence
      rates (LRRs) were 4.5% and 9.1%, respectively, in BBC patients, as against 3.3%
      and 7.6% for UBC after BCT. The 5- and 10-year distant metastasis rates were
      26.9% and 50.7%, respectively, for BBC as against 13.4% and 21.1% for UBC after
      BCT (P=0.065 and P=0.014, respectively). The 5- and 10-year disease-specific
      survival (DSS) rates for the 1705 patients were 82.1% and 41%, respectively,
      after BBC, and 91.4% and 84% after UBC (P=0.086 and P=0.0045, respectively).
      Patients with BBC have a higher rate of distant metastasis and a worse DSS than
      those with UBC. As the LRR is similar for BBC and UBC, BCT is not contraindicated
      in BBC. The incidence of BBC is low, at 1.5% which makes it difficult to reach
      any more definitive conclusions on outcome and treatment.

PMID- 14659336
TI  - Prognosis of bilateral synchronous breast cancer in Vaud, Switzerland.
AB  - Out of 6084 first breast cancers registered between 1974 and 1993 in the Cancer
      Registry of the Swiss Canton of Vaud, 81 (1.3%) were synchronous bilateral breast
      cancers (BBCs). The 5-year relative survival rates were 73% for women with
      unilateral breast cancer (UBC) and 65% for those with synchronous BBC. The
      corresponding 10-year figures were 59% and 51%. This large, population-based
      series indicates that women with synchronous BBC have a moderately lower long
      term survival than women with UBC.

PMID- 14659337
TI  - Predicting the HER2 status of breast cancer from basic histopathology data: an
      analysis of 1500 breast cancers as part of the HER2000 International Study.
AB  - The tests that are currently available for the measurement of overexpression of
      the human epidermal growth factor-2 (HER2) in breast cancer have shown
      considerable problems in accuracy and interlaboratory reproducibility. Although
      these problems are partly alleviated by the use of validated, standardised
      'kits', there may be considerable cost involved in their use. Prior to testing it
      may therefore be an advantage to be able to predict from basic pathology data
      whether a cancer is likely to overexpress HER2. In this study, we have correlated
      pathology features of cancers with the frequency of HER2 overexpression assessed
      by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence
      in situ hybridisation (FISH) has been used to re-test the equivocal cancers and
      interobserver variation in assessing HER2 overexpression has been examined by a
      slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress
      HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an
      equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+
      cancers for which complete data was available, 149 (95.5%) were ductal NST and
      152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular
      carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of
      carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the
      IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene
      amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing
      gene amplification. Circulating slides for the assessment of HER2 score showed a
      moderate level of agreement between pathologists (kappa 0.4). As a result of this
      study we would advocate consideration of a triage approach to HER2 testing.
      Infiltrating lobular and special types of carcinoma may not need to be routinely
      tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have
      been shown to overexpress HER2. Testing of these carcinomas may be performed when
      HER2 status is required to assist in therapeutic or other clinical/prognostic
      decision-making. The highest yield of HER2 overexpressing carcinomas is seen in
      the grade 3 NST subgroup in which 24% are positive by IHC.

PMID- 14659338
TI  - Histamine and epidermal growth factor in women with fibrocystic changes of the
      breast.
AB  - In this study, the blood serum concentrations of histamine (HA) and epidermal
      growth factor (EGF) of women with fibrocystic changes (FCCs) of the breast were
      estimated. The control group comprised 32 women (mean age 44.9+/-4.4 years)
      without any pathologic changes in their breasts. The study group was made up of
      81 women (mean age 44.5+/-3.5 years) with FCCs. The changes were divided into
      three subtypes: fibrous, cystic, and fibrocystic. In women with FCCs the
      concentrations of HA (P<0.01) and EGF (P<0.01) were significantly higher than in
      women without any changes in their breasts (control group). The concentration of
      EGF in blood serum was significantly higher in women with the fibrocystic subtype
      of FCC (P<0.001) than in healthy women. No correlations between the blood serum
      concentrations of HA and of EGF were found in either the control group or the
      study group. The significantly higher blood serum concentrations of HA and EGF
      women with FCCs than in healthy women suggest that HA and EGF have a role in the
      development of this disease.

PMID- 14659339
TI  - Significance of serum vascular endothelial growth factor, insulin-like growth
      factor-I levels and nitric oxide activity in breast cancer patients.
AB  - Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic
      activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I
      (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We
      measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with
      metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF
      and IGF-I levels were higher in patients with metastatic disease than in those
      with nonmetastatic disease or in controls (P<0.001). Serum nitrate+nitrite levels
      were higher in patients with metastatic and nonmetastatic disease than in
      controls (P<0.001). Patients with visceral metastasis and local metastasis had
      higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis
      (P<0.05). In the metastatic disease group, there was a positive correlation
      between serum VEGF levels and nitrate+nitrite levels (r=0.436, P<0.05). Within
      the group with nonmetastatic disease, premenopausal patients had higher serum IGF
      I levels than did postmenopausal patients (P<0.001). NO may involve an angiogenic
      process that is stimulated by VEGF in breast carcinoma. Larger studies are
      required to clarify these suggestions.

PMID- 14659340
TI  - Clinicopathological study of the expression of hsp27, pS2, cathepsin D and
      metallothionein in primary invasive breast cancer.
AB  - Expression of the hormone-related proteins hsp27, pS2, and also of cathepsin D
      (CD) and metallothionein (MT) was studied by immunohistochemistry and analyzed
      against clinical data in breast cancer. Archived material of paraffin-embedded
      breast carcinoma tissues from a cohort of 134 patients with primary invasive
      breast cancer was used. Hsp27 and pS2 (>10% of tumor cells stained) were found to
      be expressed in 63.6% and 37.6% of cases, respectively, and were correlated
      negatively with grading (P=0.006 and 0.01) and positively with estrogen receptors
      (ER) (P=0.04 and 0.04). pS2 expression was correlated with lymph node status
      (P=0.02), tumor size (P=0.01), progesterone receptor (PR) content (P=0.02), hsp27
      (P=0.015) and bcl-2 protein (P=0.001). An inverse relationship between pS2
      expression and the expression of p53 protein (P=0.005) and proliferation
      associated index MIB1 (P<0.0001) was noted. Stromal cathepsin D was positively
      correlated with tumor grade (P=0.01), PCNA (P=0.007), MIB1 (P=0.001) and p53
      (P=0.01), and negatively with ER (P=0.04) and bcl-2 (P<0.0001). MT was correlated
      positively with stromal CD (P=0.007) and inversely with PgR (P=0.04). Univariate
      analysis showed CD expression to be a positive prognostic factor for survival
      (P=0.035), with borderline significance, while MT was more strongly positive
      (P=0.01). However, none of the proteins studied was found to be related to
      disease outcome in univariate analysis. Our data show that hsp27, pS2 and stromal
      CD expression may reflect tumor differentiation and the functional status of ER
      in breast cancer, but stromal CD and tumor MT expression were the only factors
      found that may be of limited prognostic value.

PMID- 14659341
TI  - A simple tool for identifying unaffected women at a moderately increased or
      potentially high risk of breast cancer based on their family history.
AB  - Family history of breast cancer is a more important aspect of clinical management
      following the discovery of the genes BRCA1 and BRCA2. The authors developed a
      short questionnaire to categorize risk according to breast cancer history in
      close relatives. It was completed by 559 women attending for screening mammograms
      in Sydney, Australia. Twenty-three per cent reported a family history sufficient
      to be classified at a moderately increased or potentially high risk according to
      national guidelines (category II or III). Only 29 women (5%) made errors such
      that their risk category could not be determined. Validation of responses from 89
      women, 44 from category II or III, found 100% agreement with classification after
      interview by a genetic counsellor. This questionnaire has the potential to
      accurately triage risk based on a woman's knowledge of her family history, and
      could be used in a variety of settings to identify women who may require further
      assessment, management and referral advice.

PMID- 14659342
TI  - A case-control study of breast cancer and dietary intake of individual fatty
      acids and antioxidants in Montreal, Canada.
AB  - This case-control study was conducted among French-Canadians to assess the
      association between breast cancer risk and specific fatty acids, and to
      investigate if breast cancer risk associated with individual polyunsaturated
      fatty acids differs in regard to antioxidant intakes. A total of 414 cases and
      429 population-based controls were interviewed between 1989 and 1993. Dietary
      intake was assessed by a food-frequency questionnaire. No overall association was
      found between specific fatty acids and breast cancer risk, after adjustment for
      risk factors and total energy intake. In postmenopausal women with low vitamin E
      intake, there was an inverse and dose-dependent relationship between arachidonic
      acid and breast cancer risk [odds ratio (OR)=0.41; 95% confidence interval (CI)
      (0.20-0.82); P=0.02], while those with high vitamin E intake exhibited a
      significantly elevated risk [OR=2.46; 95% CI (1.12-5.39); P=0.024] when comparing
      the upper to the lower quartiles. The possible role of the interaction effect
      between arachidonic acid and vitamin E in breast cancer risk requires further
      investigation.

PMID- 14659343
TI  - Audit of compliance to adjuvant chemotherapy and radiotherapy guidelines in
      breast cancer in a cancer network.
AB  - The North Trent Cancer Network Breast Group in the United Kingdom revised its
      adjuvant treatment guidelines in breast cancer management in 1998. We aimed to
      check the compliance to the guidelines, 8 months after their introduction. Data
      were collected, retrospectively, from the medical records of patients with
      invasive breast cancer who underwent definitive surgery (in a 3-month period) in
      different cancer units and the cancer centre within the North Trent Cancer
      Network. The overall compliance to treatment guidelines was 82% (90% and 74% for
      chemotherapy and radiotherapy, respectively), which was similar across the
      network. In 5% of cases, compliance could not be determined. On case review, 22%
      of the non-compliant incidents were justified and 16% seemed to be due to
      variation in guideline interpretation. We discuss the possible reasons for non
      compliance and show a need to periodically monitor compliance to adjuvant
      treatment guidelines.

PMID- 14659344
TI  - Effects of a progestogen on normal human breast epithelial cell apoptosis in
      vitro and in vivo.
AB  - Many investigators have reported cyclic proliferation of normal human breast
      epithelial cells. A delicate balance between proliferation and apoptosis
      (programmed cell death) ensures breast homeostasis. Both the follicular and
      luteal phases of the menstrual cycle are characterized by proliferation, whereas
      apoptosis occurs only at the end of the latter phase. In this study, we observed
      that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but
      not continuous treatment with it, induced apoptosis of normal human breast
      epithelial cells in vitro and in women who applied NOMAC gel to their breasts.
      Furthermore, this apoptotic response was specific to normal breast cells, since
      withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of
      fibroadenoma cells in women. These observations open up new perspectives in the
      prevention of hyperplasia and breast cancer.

PMID- 14659345
TI  - Radioisotope for occult lesion localisation (ROLL) of the breast does not require
      extra radiation protection procedures.
AB  - AIM OF STUDY: Dosimetry data from patients and hospital personnel involved in the
      use of radioisotope for occult lesion localisation (ROLL) of the breast were
      collected to determine the need for extra radiation protection procedures.
      METHODS: Sixty-three patients have been enrolled to date into a randomised trial
      evaluating ROLL. Two megabecquerels of (99m)Tc- MAA in a syringe was mixed with X
      ray contrast medium; this was injected directly into the lesion under image
      guidance. A gamma-detecting probe (Neo-Probe) was used to locate the area of
      radioactivity. Radiation doses to all staff groups were estimated using time and
      motion studies and dose rate measurements at a range of distances during each
      stage of ROLL. RESULTS: The finger dose [FD](+/-95% CI) was considered to be the
      critical variable for surgeons and radiologists. Surgeon FD=9.3+/-3.3 microSv,
      Radiologist FD=0.5+/-0.13 microSv. Whole body doses [WBD](+/-95% CI) were
      estimated for other staff groups. Nurse WBD=0.4+/-0.4 microSv, porter WBD: nil,
      contamination and waste: nil. CONCLUSIONS: In the case of a surgeon performing
      100 procedures per annum, a FD dose of approximately 1 mSv is received, well
      within the annual dose limit of 150 mSv. Annual WBD to assisting staff may reach
      0.04 mSv, compared to an annual limit of 6 mSv. These low doses and the lack of
      contamination of radioactive waste indicate that no additional radiation
      protection measures are required.

PMID- 14659346
TI  - The use of sentinel node biopsy in the treatment of cancer of an accessory
      breast.
AB  - A patient with an accessory breast on the anterior abdominal wall was found to
      have cancer of this tissue, because of its unusual position it was decided that
      lymphatic mapping was necessary to identify the lymphatic drainage of this
      tumour. A metastasis was found in a sentinel node deep to the 'true' ipsilateral
      breast; however, the sentinel node identified in the axilla of this patient was
      free of metastases. The use of the sentinel node technique up staged the cancer
      from I to II and the patient went on to have adjuvant treatment with
      chemotherapy. The use of lymphatic mapping and sentinel node biopsy in the case
      of cancer of an accessory breast allows more accurate determination of lymph node
      status.

PMID- 14659347
TI  - Male breast cancer in World War II aviation: a case report and review.
AB  - Increased incidence of malignancies within aviators is well documented.
      Commercial female flyers have been found to have a higher risk of developing
      breast cancer. However, there has not been any report of male breast cancer
      related to flying either alone or where malignant melanoma and other primary
      cancers are also associated. We report two male World War II, British Royal Air
      Force pilots with primary breast carcinoma associated with two other primary
      cancer sites.

PMID- 14659349
TI  - A qualitative study looking at the psychosocial implications of bilateral
      prophylactic mastectomy.
AB  - The study objective was to explore the attitudes and beliefs of women at high
      risk of developing breast cancer who accepted or declined bilateral prophylactic
      mastectomy (BPM). This qualitative study employed semi-structured interviews of
      60 women who opted for BPM and 20 women who declined. Interviews took place in
      the women's own homes. Qualitative analysis led to the generation of a number of
      categories that provided conceptualisation of the women's primary experiences.
      These categories included: anxiety; surgery; sexual impact; information; gene
      testing; reconstruction and support. The study revealed that there is a clear
      need for information to be written specifically for this patient group and that
      emotional support for high-risk women offered BPM should be provided.

PMID- 14659350
TI  - Breast density and breast cancer risk factors in a high-risk population.
AB  - This study investigates relationships between familial and hormonal risk factors
      and breast density in women at high risk of developing breast cancer. The
      subjects are a subset of 102 women from the international breast cancer
      intervention study (IBIS), for whom a series of repeated measurements of breast
      density were available. Details of familial and hormonal risk factors for breast
      cancer were collected at entry and multivariate ordered logistic regression used
      to identify risk factors for increased breast density. Lower body mass index and
      nulliparity were associated with high breast density, whereas smoking was
      associated with lower breast density. It is not yet known whether a reduction in
      breast density will lead to a corresponding reduction in breast cancer risk, so
      we propose that changes in breast density be investigated as a potential early
      indicator of efficacy in chemoprevention trials for breast cancer.

PMID- 14659351
TI  - Comparison of FDG-PET and dynamic contrast-enhanced MRI in the evaluation of
      suggestive breast lesions.
AB  - The aim of our study was a direct comparison of the ability of positron-emission
      tomography with FDG-PET and of magnetic resonance imaging (MRI) to determine
      whether breast lesions were benign or malignant and of the two imaging methods
      capability of depicting eventual multifocal disease. We performed both PET and
      MRI in 36 patients (40 lesions) who were scheduled for surgery because of
      suggestive mammographic, sonographic and/or clinical findings. A final
      histological classification was available for all lesions. Tumour size ranged
      from 5 to 45 mm (mean 16.7 mm). Sensitivity for lesions, sensitivity for
      patients, specificity for lesions and specificity for patients were 68.0%, 76.2%,
      73.3%, and 73.3% for PET and 92.0%, 95.2%, 73.3%, and 73.3% for MRI,
      respectively. MRI was more sensitive than FDG-PET in disclosing malignant breast
      tumours and was also more accurate than FDG-PET in the assessment of multifocal
      disease. The lower sensitivity of FDG-PET than of MRI seems to be due to
      difficulties in reliable imaging of carcinomas smaller than 10 mm and of lobular
      carcinomas.

PMID- 14659352
TI  - Surgical treatment for invasive lobular carcinoma of the breast.
AB  - The management and outcome of 131 women with infiltrating lobular carcinoma
      treated in the Belfast City Hospital between October 1987 and February 1999 were
      reviewed. Two patients had primary hormonal treatment and were excluded from the
      statistical analysis, and 129 patients were followed up. Fifty-four patients
      (41%) had initial breast conservation surgery, which was followed by re-excision
      of margins in eight patients (14.8%) and completion total mastectomy in 26
      patients (48.1%). The breast conservation surgery group, 28 patients (21.7%), was
      compared with the total mastectomy group, 101 patients (78.2%), after a median
      follow-up period of 90 months (range 24-160 months). The overall survival was
      68.7%. Survival analysis was performed using Kaplan-Meier and Cox regression
      which showed that lymph node involvement and tumour grade were the only variables
      affecting survival (P<0.0001, and 0.01, respectively). The type of surgery
      performed did not affect survival (P=0.42). The total number of patients who
      developed local recurrence was 17 patients (13.1%, 12 patients in the breast
      conservation surgery group and five patients in the total mastectomy group,
      P<0.0001). Kaplan-Meier analysis of local recurrence showed that the type of
      surgery (P<0.0001), patient age (P=0.02), tumour grade (P=0.002), adjuvant
      radiotherapy (P=0.013), chemotherapy (P=0.031) and hormonal treatment (P=0.003)
      significantly affected local recurrence. Cox regression analysis showed that the
      only factor significantly affecting local recurrence was the type of surgery
      performed (P=0.02). Patients who underwent mastectomy had less local recurrence
      than those who had breast conservation surgery. Local recurrence after breast
      conservation surgery is high, even with clear surgical margins and post-operative
      radiotherapy. The authors believe that total mastectomy for infiltrating lobular
      carcinoma is a safer option to control local disease, especially in younger
      patients and those with high-grade tumours. Overall survival is not affected by
      the type of surgical treatment. Local recurrence can be a late event and a long
      term follow-up is recommended.

PMID- 14659353
TI  - Increased mortality from breast cancer and inadequate axillary treatment.
AB  - BACKGROUND: The assessment of axillary nodal status remains divisive: inaccurate
      staging may result in untreated axillary disease, and appropriate adjuvant
      therapy not being delivered. The impact of inadequate axillary treatment on
      survival remains controversial. We analyse the impact of failure to adequately
      assess the axillary nodal status on survival. METHODS: All women with confirmed
      breast cancer in a 15-year period were identified, and the original pathology
      reports examined, and details of radiotherapy obtained. The survival of women by
      axillary sample size was compared to a reference group of women and corrected for
      nodal status, tumour size, age, deprivation category and speciality of treating
      surgeon. FINDINGS: Sampling less than four nodes is associated with a
      significantly increased risk of death. This cannot be due to understaging the
      extent of axillary disease nor is fully explainable by differential prescription
      of adjuvant therapies. We conclude that the survival of the women studied may
      have been adversely effected by inadequate axillary treatment.

PMID- 14659354
TI  - Combined epirubicin and vinorelbine as first-line therapy in metastatic breast
      cancer: a pilot study performed by the Danish Breast Cancer Cooperative Group.
AB  - This pilot study investigated the tolerability and efficacy of increasing doses
      of epirubicin and vinorelbine as first-line chemotherapy for metastatic breast
      cancer. Acute toxicity was manageable at all dose levels for combinations of
      epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8
      repeated every 3 weeks. Myelotoxicity was the most frequent toxic event, with a
      significant increase in grade 4 leukopenia from 0% at dose level 1 (60+15 mg/m2)
      to 26% at dose level 6 (90+25 mg/m2). Signs of acute or chronic cardiotoxicity
      grades 2-4 were seen in 15% of the patients and included arrhythmia and decreased
      function. No significant association was established between dose and
      nonhematological toxicity. Objective responses were observed in 49 of the 99
      evaluable patients (49.5%, 95% CI 39.9-59.2), 18 being complete and 31 partial
      responses. Responses were observed at all six dose levels. In conclusion, acute
      toxicity was manageable at all dose levels for combinations of epirubicin 60-90
      mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8. In the treatment of
      advanced breast cancer, improvement of the antitumor efficacy by the addition of
      vinorelbine to epirubicin remains to be demonstrated in a randomized phase III
      trial.

PMID- 14659355
TI  - Expression of cyclooxygenase-2 in fine-needle aspirates from breast carcinoma and
      benign breast diseases.
AB  - Numerous studies have demonstrated that the levels of cyclooxygenase (COX), the
      enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H(2),
      and of prostaglandins are higher in various tumors and cells during inflammation
      than in normal tissues. The aim of the present study was to analyze whether COX-2
      isoform expression was noticeably higher in fine-needle aspirates (FNA) from
      breast carcinoma than in FNA from fibroadenoma and fibrocystic breast tissue. COX
      2 expression was detected by immunocytochemical (IC) staining and was analyzed by
      microscopic scoring and computer gray-scale analysis. Evaluation of COX-2 IC
      positivity in FNA from three groups of patients (nine with breast carcinoma, nine
      with fibroadenoma, eight with fibrocystic breasts) revealed high COX-2 IC
      positivity in the majority of patients with breast carcinoma and low or absent
      COX-2 IC positivity in patients with fibrocystic breast changes. In addition, low
      or medium COX-2 IC positivity was found in the majority of patients with
      fibroadenoma, only three of these patients having high COX-2 IC positivity.

PMID- 14659356
TI  - Predicting multidrug resistance-related protein and P-glycoprotein expression
      with technetium-99m tetrofosmin mammoscintigraphy.
AB  - The purpose of this study was a retrospective survey of 40 patients with
      infiltrating ductal breast carcinoma to evaluate the relationships between the
      degree of accumulation of technetium-99m tetrofosmin (Tc-TF), multidrug
      resistance-related protein (MRP) expression and P-glycoprotein (Pgp) expression
      in breast cancer tissue. Immunohistochemical analysis (IHA) was performed on
      pathological specimens of the 40 breast cancers to determine Pgp and MRP
      expression. The results of IHA, were used as the basis for dividing the 40 breast
      cancers into four groups: A, 10 tumors with positive MRP and Pgp expressions; B,
      10 tumors with positive MRP but negative Pgp expression; C, 10 tumors with
      negative MRP but positive Pgp expression; and D, 10 tumors with negative MRP and
      Pgp expression. All 40 patients had undergone Tc-TF mammoscintigraphy to
      calculate breast cancer uptake of Tc-TF to background uptake (T/B) ratios before
      IHA and surgery/biopsy. Of the four groups, group A had the lowest T/B ratios
      (1.15+/-0.10) and group D, the highest (2.19+/-0.15) (P<0.05). The T/B ratios in
      groups B (1.36+/-0.27) and C (1.37+/-0.26) were intermediate between those of
      groups A and D. In addition, the T/B ratios were statistically significantly
      lower in group A than in group B or C, and statistically significantly higher in
      groups D than in groups B or C (P<0.05). However, no significant difference in
      T/B ratio was found between groups B and C (P>0.05). Our results indicate that Tc
      TF mammoscintigraphy is helpful for in vivo determination of Pgp and MRP
      expression in breast cancers.

PMID- 14659357
TI  - Serum adrenal androgens in women with primary operable breast cancer and their
      relationship with age and body mass index.
AB  - Several studies have found elevated levels of adrenal androgens in postmenopausal
      women and depressed levels in premenopausal women with breast cancer, suggesting
      a role for adrenal androgens in the aetiology of breast cancer. We have measured
      serum dehydroepiandrosterone sulphate and androstenedione in 81 women with
      primary operable breast cancer and 62 age-matched controls. Results showed that
      serum levels of both adrenal androgens fell significantly with age in women with
      breast cancer (P=0.003). However, no relationship was observed between serum
      adrenal androgen levels and body mass index in either women with breast cancer or
      controls. Dehydroepiandrosterone sulphate levels were elevated in postmenopausal
      women with breast cancer compared to controls, and this was not due to
      preoperative stress. No differences were observed in androstenedione levels
      between premenopausal or postmenopausal women with breast cancer and controls,
      nor were dehydroepiandrostenedione sulphate levels significantly different
      between premenopausal women with breast cancer and controls. These results
      suggest that dehydroepiandrosterone sulphate has a role in the aetiology of
      postmenopausal breast cancer.

PMID- 14659358
TI  - Primary osteosarcoma of the breast.
AB  - Primary osteosarcoma of the breast is a rare malignant tumour. We report such a
      case in a 77-year-old lady who presented with a hard lump which was clinically
      and mammographically indistinguishable from a calcified fibroadenoma. Wide local
      excision of the lesion was carried out. Detailed histological and
      immunohistochemical features of the tumour are described. Because there was no
      evidence of metastasis and adequate local excision, no further treatment was
      considered necessary and she remains disease free at 39 months.

PMID- 14659359
TI  - Adenoid cystic carcinoma of the breast in a 19-year-old girl.
AB  - A case of adenoid cystic carcinoma of the breast in a 19-year-old girl is
      presented. As this tumor has specific characteristics and diagnostic criteria,
      this case illustrates the importance of an accurate histological diagnosis.

PMID- 14659360
TI  - Third International Workshop on Earthworm Ecotoxicology: Ecological,
      physiological, and physicochemical factors in earthworm ecotoxicology.

PMID- 14659361
TI  - Measurement of annetocin gene expression: a new reproductive biomarker in
      earthworm ecotoxicology.
AB  - The emergence of new technologies from the genomics revolution will transform the
      potential application of biomarkers to assess how pollutants impact people,
      animals, and ecosystems. Genetic databases provide a huge resource from which
      candidate molecular biomarkers can be identified and, subsequently, exploited to
      address these issues. However, a major challenge is to link these novel molecular
      indices to ecologically relevant whole-organism life-cycle traits (such as
      reproduction and growth). Such a functional link is provided by annetocin,
      previously characterized as a member of the vasopressin/oxytocin superfamily of
      neuropeptides. It is expressed in annelid worms within the neurons of the central
      nervous system and has been shown to be involved in the induction of egg-laying
      behavior. This paper outlines the validation of annetocin as a novel biomarker of
      reproductive fitness in the earthworm Eisenia fetida. The design of primer pairs
      targeted toward oligochaete annetocin has facilitated the isolation of a full
      length annetocin cDNA from this species. Optimization of a real-time quantitative
      PCR procedure exploiting the fluorescent DNA-binding molecule, Sybr Green, has
      allowed the measurement of annetocin transcript levels over a range covering six
      orders of magnitude. Using this approach, gene expression was measured in
      earthworms exposed to soils polluted with high concentrations of zinc and lead.
      Traditional growth and reproductive indices, including cocoon production, were
      also recorded and related to the molecular parameter. The future use of annetocin
      as a molecular genetic biomarker in terrestrial ecotoxicology is discussed.

PMID- 14659362
TI  - Differential metallothionein expression in earthworm (Lumbricus rubellus)
      tissues.
AB  - This article describes the immunoperoxidase localization of metallothionein (MT)
      in the major organs and tissues of the earthworm Lumbricus rubellus sampled from
      a mine soil heavily polluted with Pb, Zn, and Cd. The polyclonal antiserum used
      was raised against the MT isoform (wMT2), the molecular characteristics and focal
      subcellular distribution of which indicate a primary role for it in the
      sequestration of certain nonessential metals, such as Cd. Intense MT
      immunostaining was detectable in chloragogenous tissue throughout the body:
      around the intestine, in the typhlosolar infolding, around blood vessels anterior
      and posterior to the crop/gizzard, and around the calciferous gland. Electron
      probe X-ray microanalysis of neutral red-labeled vesicular structures in the
      chloragogenous tissue indicated that this acidic compartment, probably lysosomal,
      yielded the strong Cd and S signals associated with Cd-MT. MT expression was also
      detected in the apical cytoplasm of intestinal epithelial cells; in coelomocytes
      contiguous with chloragocytes attached to the gut; within the narrow tubular
      region of nephridia, in the secretory epithelia of the calciferous gland, but not
      anywhere in the body wall. We concluded that (a) the main route of Cd uptake is
      probably via absorptive alimentary surfaces, and not across the external
      epidermal layer; (b) nephridia are involved with Cd excretion and/or are a major
      target of Cd-induced pathological damage; (c) tentatively, a combination of
      immunohistochemistry and proton-induced X-ray emission analysis indicated that
      the calciferous gland is probably not a major "heavy metal" excretory route.

PMID- 14659363
TI  - A review of lysosomal membrane stability measured by neutral red retention: is it
      a workable earthworm biomarker?
AB  - The ability of biomarkers to integrate effects of chemicals on biota has lead to
      increased calls for their application in assessing the status of polluted
      ecosystems. In tandem there has been an increase in our knowledge of the
      ecophysiological responses of keystone species to pollutants, which has allowed
      the development of a number of promising methods. In contrast to the number of
      biomarker development studies, the number of biomarker validation studies has
      remained limited. This paper redresses this imbalance by drawing together data
      from studies that have used the earthworm lysosomal membrane stability response
      (measured using the neutral red retention assay). This review first gives a short
      history of the biomarker's development. Second, it sets published applications of
      the technique against established criteria for a "good" biomarker (i.e., dose
      response relationship, sensitivity, ecological relevance, confounding factors,
      chemical specificity, species differences, time-response relationship,
      methodological concerns, and overall public/regulator confidence, and
      acceptance). Discussion of the biomarker's suitability to each criterion is
      followed by an overall evaluation of its workability for routine soil quality
      assessment and caveats for its use.

PMID- 14659364
TI  - Modeling ingestion as an exposure route for organic chemicals in earthworms
      (Oligochaeta).
AB  - Earthworms take up chemicals from both soil pore water and food, but the
      quantitative contribution of each route is unclear. In this paper, a model is
      presented for the accumulation of organic chemicals in earthworms, including a
      compartment for the gut contents. A Monte Carlo screening method is used to
      calibrate the model simultaneously to four experimental data sets for
      hexachlorobenzene (HCB) in the compost worm (Eisenia andrei). The calibration
      procedure shows that the dominant route of exposure is across the gut wall.
      Nevertheless, predicted body residues of HCB are generally no more than 20%
      higher than the estimate based on equilibrium partitioning (EP), independent of
      the uncertainties in all of the model parameters. The deviation from EP is mainly
      related to the digestive efficiency of the earthworm. Body residues are not
      expected to exceed the EP estimate by more than 50% for other chemicals or other
      earthworm species. The model is particularly useful when the organism's food
      source is specifically contaminated and EP cannot be applied.

PMID- 14659365
TI  - The bioavailability of chemicals in soil for earthworms.
AB  - The bioavailability of chemicals to earthworms can be modified dramatically by
      soil physical/chemical characteristics, yet expressing exposure as total chemical
      concentrations does not address this problem. In order to understand the effects
      of modifying factors on bioavailability, one must measure and express chemical
      bioavailability to earthworms in a consistent, logical manner. This can be
      accomplished by direct biological measures of bioavailability (e.g.,
      bioaccumulation, critical body residues), indirect biological measures of
      bioavailability (e.g., biomarkers, reproduction), or indirect chemical measures
      of bioavailability (e.g., chemical or solid-phase extracts of soil). If indirect
      chemical measures of bioavailability are to be used, they must be correlated with
      some biological response. Bioavailability can be incorporated into ecological
      risk assessment during risk analysis, primarily in the estimation of exposure.
      However, in order to be used in the site-specific ecological risk assessment of
      chemicals, effects concentrations must be developed from laboratory toxicity
      tests based on exposure estimates utilizing techniques that measure the
      bioavailable fraction of chemicals in soil, not total chemical concentrations.

PMID- 14659366
TI  - Manganese toxicity in soil for Eisenia fetida, Enchytraeus crypticus
      (Oligochaeta), and Folsomia candida (Collembola).
AB  - The U.S. Environmental Protection Agency is developing Ecological Soil Screening
      Level (Eco-SSL) benchmarks for ecological risk assessment (ERA) of contaminants
      at Superfund sites. Eco-SSLs are developed from published values whenever
      sufficient quantity and quality of data exist. Because insufficient information
      was available to generate an Eco-SSL for Mn, standardized toxicity testing was
      undertaken to fill the data gaps. Tests included the earthworm (Eisenia fetida)
      cocoon production test, the enchytraeid (Enchytraeus crypticus) reproduction
      test, and the collembolan (Folsomia candida) reproduction test, all conducted in
      Sassafras sandy loam soil that supports a relatively high bioavailability of
      metals. Weathering and aging of manganese-amended soil were carried out to more
      closely simulate exposure effects at Superfund sites on soil invertebrates. Data
      were analyzed by nonlinear regression to determine EC20 and EC50 values based on
      concentration-response relationships. The toxicity order for manganese in
      Sassafras sandy loam was E. crypticus>E. fetida>F. candida, with EC20 values of
      116, 629, and 1209 mg kg(-1), respectively. The Eco-SSL requirement for the
      testing of multiple representative species is well justified. All study results
      will be submitted to the Eco-SSL Task Group for quality control review prior to
      inclusion in the Eco-SSL database.

PMID- 14659367
TI  - Responses of earthworms (Lumbricus rubellus) to copper and cadmium as determined
      by measurement of juvenile traits in a specifically designed test system.
AB  - In this study, the effects of two metals, copper and cadmium, on the growth and
      development of juvenile Lumbricus rubellus were measured in a toxicity test in
      which individuals were grown in isolation. This design had a number of advantages
      over traditional test systems for earthworms. Importantly, the test is
      specifically designed to measure two juvenile traits (survival over and length of
      the juvenile period) that have been shown to have a high sensitivity for
      determining population growth rate. The test system also maximizes replication,
      while allowing time-series-based monitoring of individual growth. For both
      metals, significant exposure-dependent effects on survival, growth, development
      time, and (less certainly) maturation weight were observed. Comparisons of the
      relative toxicity of the two metals indicated different concentration-response
      relationships. For copper, hormesis was found at low levels, while only at the
      highest soil concentration tested (10.07 micromol g(-1)) were (severe) toxic
      effects present. For cadmium, hormesis was also evident at the lowest
      concentration tested; however, at soil levels above this, a graded concentration
      dependent toxic effect was apparent. These differences in the exposure response
      patterns can be (tentatively) explained in terms of the mechanisms for handling
      copper (an essential metal for earthworms) and cadmium (a putative nonessential
      element). The applicability of the test for routine measurement of chemical
      effects on ecologically relevant juvenile traits is also outlined and future
      developments are discussed.

PMID- 14659369
TI  - Assessing 2,4,6-trinitrotoluene (TNT)-contaminated soil using three different
      earthworm test methods.
AB  - Within the scope of a phytoremediation project, the toxicity of 2,4,6
      trinitrotoluene (TNT) contaminated soil (and its toxic metabolites) on earthworms
      was assessed. In addition to the standard acute and reproduction tests (ISO
      11268), an avoidance response test was applied. The test methods covered all
      important ecological relevant endpoints (acute, chronic, behavioral). At a
      concentration of 1142 mg/kg, TNT caused significant toxic effects in all test
      methods, but at lower test concentrations no significant acute or reproduction
      toxic effects could be observed. The avoidance response test, however, showed
      significant repellent effects at a concentration of 29 mg/kg TNT and therefore
      proved to be more sensitive than the other tests in this case. Results of the
      earthworm tests compared well with results of an ecotoxicological biotest
      battery. Thus, earthworm toxicity tests are useful tools for terrestrial risk
      assessment but require a hierarchy of test designs that differ in effect levels
      (behavior, sublethal, lethal). Whereas higher concentrations of a pollutant can
      easily be assessed with the acute test (which requires lethal concentrations to
      show an effect), contaminated soils with lower (sublethal) pollutant
      concentrations require more sensitive test methods such as reproduction or
      behavioral tests in their risk assessment.

PMID- 14659368
TI  - Sublethal soil copper concentrations increase mortality in the earthworm
      Aporrectodea caliginosa during drought.
AB  - Simultaneous effects of drought and a sublethal concentration of copper on the
      earthworm Aporrectodea caliginosa were investigated in the laboratory.
      Experiments were performed with exposure to 150 mg Cu kg(-1) dry soil and
      different levels of drought during a 3-wk period. Soil water potentials from pF
      1.5 (wet) to pF 5 (very dry) were obtained. The soil water potential resulting in
      50% mortality was significantly reduced from pF 4.48 in worms not exposed to
      copper to pF 4.09 in copper-exposed worms, thus demonstrating synergy-like
      effects of drought and copper. Development of estivation cells was significantly
      depressed in copper-exposed worms compared to worms not exposed to copper. For
      all drought levels (except the highest, where 100% mortality occurred), copper
      exposed earthworms with no estivation cells had more than twice as high mortality
      and, at severe drought exposure, also lower water content than those which had
      developed the estivation cells. With increasing drought level, the whole-body
      burden of copper increased from about 40 microg Cu g(-1) dry weight to about 90
      microg Cu g(-1). When the worms were exposed to drought, the osmolality in their
      body fluids increased. This was due to a greater concentration of already
      existing solutes resulting from extensive loss of water, and not to mobilization
      or synthesis of additional solutes.

PMID- 14659370
TI  - Heavy metal concentrations in Enchytraeidae (Oligochaeta) in the Niepolomice
      Forest.
AB  - Enchytraeidae were investigated as a part of a broad study of Niepolomice Forest
      ecosystem functioning. Animals were collected in oak-hornbeam (Tilio-Carpinetum)
      and in mixed oak-pine (Pino-Quercetum) stands. The highest cadmium concentration
      was observed in oak-hornbeam from the northern part of the forest (32.33+/-23.22
      mg kg(-1) dry mass), with lower ones in mixed oak-pine (13.60+/-21.42 mg kg(-1)
      dry mass) and southern oak-hornbeam stands (11.84+/-7.52 mg kg(-1) dry mass).
      Lead concentrations were higher in mixed oak-pine (47.73+/-23.36 mg kg(-1) dry
      mass) and southern oak-hornbeam (52.20+/-45.19 mg kg(-1) dry mass) stands than in
      northern, oak-hornbeam (9.20+/-6.46 mg kg(-1) dry mass). The copper concentration
      was similar in animals from all forest types studied (147.94+/-106.38 mg kg(-1)
      dry mass in mixed oak-pine, 138.35+/-64.76 mg kg(-1) dry mass in northern oak
      hornbeam, and 138.27+/-80.08 mg kg(-1) dry mass in southern oak-hornbeam). The
      lowest concentration of zinc in animals was found in northern oak-hornbeam
      (1015.27+/-300.28 mg kg(-1) dry mass) and higher concentrations, in mixed oak
      pine (2233.81+/-1825.41 mg kg(-1) dry mass) and southern oak-hornbeam (2366.60+/
      1987.52 mg kg(-1) dry mass). The concentrations of available metals in litter
      trended with those in the animals, but only the relation between lead
      concentration in animals and available lead in litter was significant. The
      spatial distribution of metal concentrations in the whole forest suggests a
      relationship between forest type and the content of cadmium, lead, and zinc in
      animals. The spatial distribution of heavy metal content in enchytraeids was
      investigated in selected plots as well. The coefficients of variation indicated
      that lead had the most diverse distribution and zinc the most homogeneous.

PMID- 14659372
TI  - Recommendations of the 3rd International Workshop on Earthworm Ecotoxicology,
      Aarhus, Denmark, August 2001.

PMID- 14659371
TI  - Pesticide-induced surface migration by lumbricid earthworms in grassland: life
      stage and species differences.
AB  - Pesticide-induced changes in surface migration by earthworms in grassland were
      investigated using trapping and the fungicide benomyl. Traps were tended daily
      for 15 days after spraying, resulting in 2152 earthworms, five species, and
      juvenile predominance which reflected species/life-stage composition in the soil.
      Significant increases in migration (all worms) occurred already by day 2 due to
      spraying, final treatment level being 2.8 x control. Life-stage composition
      indicated an increased juvenile proportion from 55% to 75% due to treatment.
      Spraying caused surfacing juveniles to increase significantly by day 2, reaching
      a final level 3.8 x control, whereas for mature worms a significant increase did
      not occur until day 4. Species rank-order was Aporrectodea longa>A.
      rosea>Lumbricus terrestris>A. caliginosa in control areas, but A. longa>L.
      terrestris>A. rosea>A. caliginosa in sprayed areas; spraying altered the rank
      order such that the anecic A. longa and L. terrestris dominated, jointly
      increasing from 59% to 78%. At species level, L. terrestris and A. longa
      exhibited significant increases of 4.6 x and 3.6 x in final migration levels in
      treated areas, the endogeic A. rosea and A. caliginosa having trends for
      increase. Species-specific differences for reaction time occurred, with
      significantly elevated migration already by day 1 for L. terrestris, and day 2
      for A. longa and A. caliginosa. For each species, juveniles consistently showed
      greater increases than mature worms due to spraying, significantly so for
      juvenile L. terrestris, A. longa, and A. caliginosa, the two anecics reaching as
      high as 5.3 x and 4.7 x. The response of mature worms differed: A. longa and A.
      rosea increased surfacing due to treatment, L. terrestris showed a delayed
      reaction, whereas A. caliginosa exhibited suppressed migration. Results are
      discussed relative to behavior, ecological category, and risk of toxic exposure.

PMID- 14659374
TI  - Is integrated medicine respectable?

PMID- 14659375
TI  - Bringing together the orthodox and alternative in health care.
AB  - This paper charts the developing historical relationship between orthodox and
      alternative medicine in Britain, focusing on the work of health practitioners. It
      begins by defining the concepts of orthodox and alternative medicine, noting that
      this was not really a meaningful distinction until the mid-nineteenth century
      with the rise of the medical profession. Before this time there was a relatively
      undifferentiated playing field. Thereafter doctors gained state-underwritten
      professional standing, with alternative therapists becoming increasingly
      marginalised by the mid-twentieth century. However, in the wake of the medical
      counterculture of the 1960s and 1970s there has been growing public interest in
      alternative medicine coupled with an associated increase in the numbers of its
      practitioners, particularly in the private sector. Despite initial resistance,
      alternative medicine has now gained greater acceptance by medical orthodoxy. The
      paper concludes by considering how orthodox and alternative health care can be
      brought together in more integrated fashion in the future-for the benefit of the
      wider public.

PMID- 14659376
TI  - Methodology for the scientific evaluation of complementary and alternative
      medicine.
AB  - It has been suggested that CAM research should establish efficacy before
      examining mechanism. This paper shows that the efficacy-mechanism distinction is
      a false one, as any test of efficacy assumes a particular mechanism and is a test
      of the theory underlying that mechanism. The term RCT is currently used in
      medicine for two different sorts of study. The randomised controlled trial
      (RConT) requires an experimental manipulation that can 'control' for the
      mechanism under consideration, and therefore tests the efficacy of that
      mechanism. The randomised comparison trial (RComT) requires only an experimental
      manipulation creating a therapeutically relevant comparison, and tests the
      effectiveness of that therapy. The ability to achieve control coupled with an
      assumed implausibility of hidden moderating variables characterises drug therapy
      and some CAM therapies where the RConT can be used. However, other CAM
      researchers assume a variety of holistic mechanisms, where control is necessarily
      poor and the hypothesis of complex interactions suggest the existence of multiple
      moderators. In these cases other experimental (e.g. RComT), quasi-experimental or
      non-experimental designs are needed to evaluate therapeutic practice. Researchers
      from both communities should make explicit their underlying assumptions and the
      mechanisms they seek to evaluate when carrying out empirical studies. Research
      design needs to be appropriate for the mechanism under test.

PMID- 14659377
TI  - Invited commentary on Hyland ME: methodology for the scientific evaluation of
      complementary and alternative medicine.

PMID- 14659378
TI  - Exploring the relationship between women's health and the use of complementary
      and alternative medicine.
AB  - In this paper we identify the need for further research exploring the
      relationship between complementary and alternative medicine (CAM) use and women's
      health. We offer our personal thoughts on the direction such future research
      might take outlining a number of research domains (type of CAM consumption,
      longitudinal analysis of women's use of CAM, cross-cultural analysis of women's
      CAM consumption, reasons for women's CAM consumption). We hope that this brief
      paper helps inspire greater research attention upon what we believe to be a well
      deserving sub-field of study within the social science of CAM.

PMID- 14659379
TI  - Effects of Qi-therapy on blood pressure, pain and psychological symptoms in the
      elderly: a randomized controlled pilot trial.
AB  - Recently, we reported that Qi-therapy may be beneficial in reducing negative
      psychological symptoms and increasing melatonin levels, neutrophil function and
      natural killer cell cytotoxicity in young subjects. However, there is little
      scientific evidence of its efficacy in elderly subjects. Therefore, this study
      was designed to investigate the effects of Qi-therapy on anxiety, depression,
      fatigue, pain and blood pressure in elderly subjects. Ninety-four elderly
      subjects were randomly assigned to either Qi-therapy (n=47) or mimic therapy
      (n=47) groups. Both groups received a 10-min intervention period once using
      similar procedures. The Qi-therapy group exhibited greater reduction in anxiety,
      depression, fatigue, pain level and blood pressure compared to the placebo group;
      the difference in anxiety was significant (P=0.014). These results suggest that
      even a brief application of Qi-therapy may exert a positive psychological and
      physiological effect. However, further research is necessary in order to fully
      understand the long-term impact of Qi-therapy on psychological health and the
      cardiovascular system.

PMID- 14659380
TI  - CAM research funding in the UK: surveys of medical charities in 1999 and 2002.
AB  - A custom-made questionnaire was sent to all UK medical charities in 1999 and
      again in 2002. Its primary aim was to assess the commitment of these institutions
      towards funding research in complementary and alternative medicine (CAM). Sixty
      two (1999) and 60 (2002) answers were received corresponding to response rates of
      62% and 55%. The total CAM research funds have increased from pound 70,000 in
      1999 to pound 412,755 in 2002. In terms of total research budgets, this amounts
      to 0.05% and 0.31%, respectively. The number of CAM research projects has
      increased but so has the number of charities who do not fund CAM research. We
      conclude from these data that CAM research funding by UK medical charities has
      increased. In relative terms it does, however, remain low and out of proportion
      to the prevalence of CAM use in the UK.

PMID- 14659381
TI  - Characteristics associated with reported CAM use in patients attending six GP
      practices in the Tayside and Grampian regions of Scotland: a survey.
AB  - OBJECTIVES: To study the nature of CAM use in primary care attenders, the
      involvement of their NHS healthcare professionals in their CAM care and
      differences in characteristics between CAM users and non-users. DESIGN: Postal
      questionnaire for primary care attenders and analysis of practice leaflets.
      SETTING: Six Scottish GP practices with a range of practice size, CAM provision
      within practice, deprivation and rurality. RESULTS: Five hundred and fourteen
      primary care attenders described 1194 incidences of CAM use and gave details
      about their main therapy. 37% had contact with a practitioner, the rest mainly
      self-prescribed. The perceived effectiveness of CAM was high. Patients used CAM
      for a variety of health problems, mainly as an adjuvant to orthodox medicine
      rather than an alternative. The involvement of the NHS in CAM delivery was small
      but there is a significant role to ensure patient safety, especially regarding
      herb-drug interactions. Disclosure rate of CAM use was low. CAM offered options
      in areas where the provision in the NHS is difficult, including musculo-skeletal
      and mental health problems. Provision of CAM by the GP is associated with higher
      CAM use in primary care attenders. CONCLUSIONS: It is recommended that healthcare
      professionals include patients' use of CAM in history taking and clinical
      decision making.

PMID- 14659382
TI  - Availability of acupuncture in the hospitals of a major academic medical center:
      a pilot study.
AB  - BACKGROUND: Acupuncture is widely used by the American public, but little is
      known about its availability and use in academic medical settings. We performed a
      pilot study to compare acupuncture services provided by hospitals affiliated with
      a major academic teaching institution, and a parallel survey of services provided
      through an acupuncture school in one city in New England. METHODS: Between
      December 2000 and July 2001, a telephone survey was conducted of the 13 hospitals
      affiliated with Harvard Medical School, and the clinics affiliated with the New
      England School of Acupuncture. RESULTS: Acupuncture was available in 8 of the 13
      hospitals. Acupuncture was provided in ambulatory clinics in all eight hospitals,
      but was available to inpatients in only one hospital. Six hospitals delivered
      acupuncture through an outpatient pain treatment service, one through a women's
      health center, one through an HIV clinic, and one hospital delivered acupuncture
      through two services; a program in the anesthesia department and a multi
      disciplinary holistic program in a primary care department. In contrast, the
      acupuncture school clinics provided services through an on-site clinic at the
      school, through acupuncture departments at two community-based hospitals, and
      through a network of 12 satellite acupuncture-dedicated clinics operating
      throughout the state. CONCLUSION: Acupuncture is available on a limited basis in
      a majority of the teaching hospitals in this city. At the acupuncture school
      clinics, there are few barriers to care. Future health care studies will need to
      examine the role of acupuncture in diverse geographic settings and to examine its
      impact on quality of care, teaching and its role in research in academic centers.

PMID- 14659384
TI  - A Conference on Developing Research Strategies in CAM.

PMID- 14659383
TI  - Oncology professionals' communication with cancer patients about complementary
      therapy: a survey.
AB  - OBJECTIVE: To compare the communication practices of three groups of oncology
      professionals with regard to discussion of complementary therapies with cancer
      patients. DESIGN: A mail survey was completed by a randomly selected, nationwide
      sample of oncology physicians, oncology nurses, and oncology social workers in
      the United States. MAIN OUTCOME MEASURES: Respondents indicated how often they
      initiated discussion of complementary therapies, their comfort level discussing
      this subject, and the perceived impact on the patient-professional relationship.
      RESULTS: Significantly more of the social workers reported that they initiated
      discussion of complementary therapy compared to physicians and nurses. Physicians
      and social workers reported being equally comfortable with this topic and more so
      than nurses. More of the social workers reported believing that discussing
      complementary therapies can enhance the patient-professional relationship.
      CONCLUSIONS: Oncology social workers were more amenable to discussing
      complementary therapies than physicians or nurses. The impact of communication on
      patient outcomes is addressed.

PMID- 14659385
TI  - St John's wort, conventional medication, and placebo: an egregious double
      standard.
AB  - The efficacy of antidepressant medication is generally thought to be well
      established, whereas that of hypericum (St John's wort) is considered doubtful.
      The data fail to support these discrepant conclusions. Instead they show that
      hypericum and conventional antidepressants are equally effective (or
      ineffective). This suggests that different standards are being used to evaluate
      the two types of treatment.

PMID- 14659400
TI  - Smallpox inoculation--should we credit Chinese medicine?

PMID- 14659406
TI  - Identification of a locus for an autosomal recessive hyaline body myopathy at
      chromosome 3p22.2-p21.32.
AB  - Hyaline body myopathy is a rare congenital disease with distinctive
      histopathological features. We performed homozygosity mapping in a family with
      two affected sibs and identified a gene locus with a maximum homozygosity region
      of 5.35 centi Morgans or 5.59 Megabases at chromosome 3p22.2-p21.32. The best
      candidate responsible for the disease is a novel gene that exhibits homology to
      the myosin heavy chain.

PMID- 14659407
TI  - Dystrophinopathy caused by mid-intronic substitutions activating cryptic exons in
      the DMD gene.
AB  - In the course of a mutation search performed by muscle dystrophin transcript
      analysis in 72 Duchenne and Becker Muscular Dystrophies (DMD/BMD) patients
      without gross gene defect, we encountered four unrelated cases with additional
      out-of-frame sequences precisely intercalated between two intact exons of the
      mature muscle dystrophin mRNA. An in silico search of the whole dystrophin
      genomic sequence revealed that these inserts correspond to cryptic exons flanked
      by one strong and one weak consensus splice site and located in the mid-part of
      large introns (introns 60, 9, 1M, and 62, respectively). In each case we
      identified an intronic point mutation activating the cryptic donor or acceptor
      splice site. The patients exhibited a BMD/intermediate phenotype consistent with
      the presence of reduced amounts of normally spliced transcript and normal
      dystrophin. The frequency of this new type of mutation is not negligible (6% of
      our series of 65 patients with 'small' mutations). It would be missed if the
      exploration of the DMD gene is exclusively performed on exons and flanking
      sequences of genomic DNA.

PMID- 14659408
TI  - A-utrophin up-regulation in mdx skeletal muscle is independent of regeneration.
AB  - Duchenne muscular dystrophy is a fatal childhood disease caused by mutations that
      abolish the expression of dystrophin in muscle. Utrophin is a paralogue of
      dystrophin and can functionally replace it in skeletal muscle. A method to induce
      utrophin up-regulation in muscle should therefore be therapeutically useful in
      Duchenne muscular dystrophy. The search for such a method needs to be informed by
      an understanding of the mechanisms controlling utrophin expression in muscle. Two
      full length utrophin isoforms are expressed: A and B. A-utrophin is up-regulated
      in dystrophin deficient skeletal muscle and we sought to test the hypothesis that
      this up-regulation occurs as a consequence of ongoing regeneration. We measured
      utrophin expression by immunohistochemistry and immunoblotting in the oesophageal
      outer muscular layer and in gamma-irradiated limb muscle from mdx mice. Skeletal
      muscle in these tissues is dystrophin deficient but not regenerating; we found
      that A-utrophin up-regulation still occurred. We conclude that utrophin up
      regulation in skeletal muscle does not depend on regeneration. An alternative
      hypothesis involving competition for binding sites between utrophin and
      dystrophin is discussed. These results have important implications for future
      studies aiming to effect therapeutic utrophin up-regulation in Duchenne muscular
      dystrophy patients.

PMID- 14659409
TI  - Electrophysiological and morphological characterization of a case of autosomal
      recessive congenital myasthenic syndrome with acetylcholine receptor deficiency
      due to a N88K rapsyn homozygous mutation.
AB  - Congenital myasthenic syndromes are rare heterogeneous hereditary disorders,
      which lead to defective neuromuscular transmission resulting in fatigable muscle
      weakness. Post-synaptic congenital myasthenic syndromes are caused by
      acetylcholine receptor kinetic abnormalities or by acetylcholine receptor
      deficiency. Most of the congenital myasthenic syndromes with acetylcholine
      receptor deficiency are due to mutations in acetylcholine receptor subunit genes.
      Some have recently been attributed to mutations in the rapsyn gene. Here, we
      report the case of a 28-year-old French congenital myasthenic syndrome patient
      who had mild diplopia and fatigability from the age of 5 years. His muscle biopsy
      revealed a marked reduction in rapsyn and acetylcholine receptor at neuromuscular
      junctions together with a simplification of the subneural apparatus structure. In
      this patient, we excluded mutations in the acetylcholine receptor subunit genes
      and identified the homozygous N88K rapsyn mutation, which has already been shown
      by cell expression to impair rapsyn and acetylcholine receptor aggregation at the
      neuromuscular junction. The detection of the N88K mutation at the heterozygous
      state in five of 300 unrelated control subjects shows that this mutation is not
      infrequent in the healthy population. Electrophysiological measurements on
      biopsied intercostal muscle from this patient showed that his rapsyn mutation
      induced fatigable weakness is expressed not only in a diminution in acetylcholine
      receptor membrane density but also in a decline of endplate potentials evoked at
      low frequency.

PMID- 14659410
TI  - Asymptomatic carriers and gender differences in facioscapulohumeral muscular
      dystrophy (FSHD).
AB  - Facioscapulohumeral muscular dystrophy is an autosomal dominant muscle disorder,
      mapped to 4q35. It is characterized by remarkable inter- and intrafamilial
      clinical variability ranging from severe phenotype to asymptomatic carriers. The
      aim of the present study was to assess the size of the Eco RI fragment in a large
      sample of asymptomatic or minimally affected carriers as well as symptomatic
      patients, comparing both sexes, in order to verify if asymptomatic carriers are
      randomly distributed or concentrated in some particular families and if there is
      preferential parental transmission (maternal or paternal) resulting in non
      penetrant carriers. We have analysed a total of 506 individuals from 106
      unrelated families with at least one affected facioscapulohumeral muscular
      dystrophy proband. In all patients the molecular diagnosis was confirmed
      following double digestion (Eco RI/Bln I fragment <35 kb). About 20% among
      probands' relatives who were found to carry the small fragment were asymptomatic
      or minimally affected, without preferential parental transmission, but with a
      significantly higher proportion of females (n=37) than males (n=14). Although
      asymptomatic carriers were found in about 30% of the families, some genealogies
      seem to concentrate more non-penetrant cases. A significant correlation between
      the size of the Eco RI fragment and severity of the phenotype was observed in the
      total sample but surprisingly this correlation is significant only among affected
      females. The gender difference in clinical manifestation as well as the
      observation that asymptomatic carriers are not rare should be taken into
      consideration in genetic counseling of affected patients or 'at-risk' relatives.

PMID- 14659411
TI  - Changes in motor cortex excitability in facioscapulohumeral muscular dystrophy.
AB  - Previous studies found that some patients with severe, early onset
      facioscapulohumeral muscular dystrophy (FSHD) present epilepsy and mental
      retardation. This suggests a functional involvement of central nervous system in
      severe FSHD. It is unknown whether minor functional changes of central nervous
      system are also present in less severe forms of FSHD. To investigate this, we
      examined the excitability of neuronal networks of the motor cortex with a range
      of transcranial magnetic stimulation paradigms in 20 FSHD patients with
      heterogeneous clinical severity and compared the data with that from 20 age
      matched healthy individuals and from 6 age-matched patients with other muscle
      diseases. There was significantly less intracortical inhibition in FSHD patients
      (mean responses +/- SD reduced to 58.1+/-43.5% of the test size) than in controls
      (mean responses +/- SD reduced to 29.3+/-13.5% of the test size; P=0.025) and in
      patients with other muscle diseases (mean responses +/-SD, reduced to 30.6+/
      11.7% of the test size; P=0.046). No significant difference was found between the
      control group and patients with other muscle diseases (P=0.970).

PMID- 14659412
TI  - A novel mutation in the mitochondrial tRNA(Phe) gene associated with
      mitochondrial myopathy.
AB  - We report a novel heteroplasmic T-->C mutation at nt position 582 within the
      mitochondrial tRNA(Phe) gene of a 70-year-old woman with mitochondrial myopathy.
      No other family members were affected, suggesting that our patient was a sporadic
      case. The muscle showed frequent ragged red fibers and 43% cytochrome c oxidase
      deficient fibers. The mutation alters a conserved base pairing in the aminoacyl
      acceptor stem. The mutation load was 70% in muscle homogenate and varied from 0
      to 95% in individual muscle fiber segments. Cytochrome c oxidase-negative fibers
      showed significantly higher levels of mutated mtDNA (>75%) than Cytochrome c
      oxidase-positive fibers (<55%). This mutation adds to the previously described
      four pathogenic mutations in the tRNA(Phe) gene.

PMID- 14659413
TI  - Muscle MRI in adult-onset acid maltase deficiency.
AB  - We report the spectrum of muscle involvement on magnetic resonance imaging in 11
      patients with a molecularly confirmed diagnosis of adult-onset acid maltase
      deficiency at different clinical stages. Muscle magnetic resonance imaging showed
      a selective progressive pattern of muscle involvement with a constant involvement
      of the adductor magnus and semimembranosus at the early stage of the disease and
      a later fatty infiltration of the long head of the biceps femoris, semitendinosus
      and of the anterior thigh muscles. In the advanced phases a selective sparing of
      sartorius, rectus, and gracilis muscles and peripheral portions of the vastus
      lateralis was also evident. Muscle strength and magnetic resonance imaging
      findings were positively correlated. The results suggest that muscle magnetic
      resonance imaging may provide valuable diagnostic guidance for the assessment of
      accurate selective muscular involvement in acid maltase deficiency and may help
      monitor the progression of the disorder. Further control studies in a larger
      cohort are needed to evaluate the specificity of these findings.

PMID- 14659414
TI  - 117th ENMC workshop: ventilatory support in congenital neuromuscular disorders --
      congenital myopathies, congenital muscular dystrophies, congenital myotonic
      dystrophy and SMA (II) 4-6 April 2003, Naarden, The Netherlands.

PMID- 14659415
TI  - 2003 International Friedreich's Ataxia Research Conference, 14-16 February 2003,
      Bethesda, MD, USA.

PMID- 14659420
TI  - Air and soil dioxin levels at three sites in Italy in proximity to MSW
      incineration plants.
AB  - Levels of polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated
      dibenzofurans (PCDF) in both air and soil samples were measured at three
      different sites in Italy, in proximity to three municipal solid waste
      incinerators (MSWIs) to determine baseline contamination and the contributory
      role of incinerator emissions. At the first site, located in an agricultural,
      cattle-breeding, typically flattish area of the Po Valley, the dioxin
      concentrations had already been measured before the start-up of the new MSWI.
      These dioxin concentrations were then again measured after two years of continual
      operation of the incinerator. Despite the presence of the plant, the PCDD/Fs
      concentrations appear not to have been affected and were found to be in a range
      of 22-125 fg I-TEQ m(-3) in the air samples and 0.7-1.5 pg I-TEQ g(-1) in the
      soil samples. The second site is located in an industrial district of the Veneto
      Region, in the surroundings of an old MSWI that is not equipped with Best
      Available Technology (BAT) dioxin removal system. The PCDD/Fs concentrations in
      the air samples were between 144 and 337 fg I-TEQ m(-3). This is a typical range
      of values for industrial areas, while the soil samples showed contamination
      levels between 1.1 and 1.4 pg I-TEQ g(-1). The third site lies in the Adige
      Valley, near a MSWI that has been equipped with BAT for flue gas cleaning. The
      observed values ranged from 10 to 67 fg I-TEQ m(-3) for the air samples and 0.08
      1.2 pg I-TEQ g(-1) for the soil samples. The contributory factors of the varying
      characteristics of the different areas together with the types of technology
      adopted at each MSWI plant are discussed. The PCDD/Fs levels are subsequently
      compared with established values from previous studies.

PMID- 14659421
TI  - The evaluation of dioxin and dioxin-like contaminants in selected food samples
      obtained from the Belgian market: comparison of TEQ measurements obtained through
      the CALUX bioassay with congener specific chemical analyses.
AB  - A limited number of different foods were analysed for dioxin-like compounds by
      the CALUX bioassay which is an in vitro luciferase reporter gene assay measuring
      chemical activation of the aryl hydrocarbon receptor. Sixty-two milk samples were
      obtained from a surveillance campaign, 34 meat samples and 34 fishery products
      were purchased from the Belgian market. Bio-analytical and chemo-analytical
      dioxin toxicity equivalents (TEQ) values of the same milk samples were compared.
      Spearman's Rank correlation coefficients of 0.72, 0.67, 0.73 were obtained
      respectively between CALUX-TEQ and PCDD/F-TEQ, DL-PCB-TEQ and PCDD/F+DL-PCB-TEQ.
      The bioassay limit of detection was 0.1 pg TEQ from 1 g animal lipid, the limit
      of quantification was 0.4 pg TEQ. The repeatability of the CALUX bioassay
      (variability of butter fat samples analysed in the same run) showed a coefficient
      of variation (CV) of 10%, intra laboratory reproducibility based on independent
      runs of the same butter fat samples showed more variation (CV of 26% for samples
      above 2 pg TEQ/g lipid). All milk samples with a chemical TEQ value above the
      current limit value in Belgium showed an elevated CALUX-TEQ concentration, above
      6 pg TEQ/g lipid. No false negative results were obtained. Based on the good
      correlation between CALUX-TEQ and chemically measured TEQ levels, the CALUX
      bioassay can be recommended as a screening tool for routine measurement of
      potentially toxic PHAHs in milk samples. Chemical analyses could then largely be
      restricted to positive samples, in order to identify the nature and to quantify
      the concentration of the chemicals that give the positive signal. Meat samples
      showed lower CALUX-TEQ values per gram lipid compared to fish samples. The fish
      samples showed a wider range of CALUX-TEQ values than the meat samples.

PMID- 14659422
TI  - Status of PCDD/F-emission control in Germany on the basis of the current
      legislation and strategies for further action.
AB  - The protection of environment from polychlorinated dibenzodioxin and -furan
      (PCDD/F) impacts, caused by a heterogeneous spectrum of thermal stationary
      sources and several others in chemical industry, bases on a comprehensive
      legislation in Germany. The results of this emission reduction strategy are
      presented by emission inventories for stationary, mainly industrial sources
      comparing in this paper data for emissions between 1994 and 2001. These results
      show that the implementation of best available techniques (BAT) at industrial
      sources for PCDD/F-reduction has been nearly fully exhausted at nearly all
      relevant sources and extensive overall emission reductions were achieved by the
      end of the 1990s. Further reductions for PCDD/F are needed for specific sources
      in metallurgical industries, especially sinter plants, and for domestic furnaces
      only. For coplanar PCBs (co-PCBs) almost no emission data are available from
      German sources; a few data from measurements of co-PCB have been published from
      two waste incineration plants. These measurements show that the emission limit
      value of 0.1 ng TEQ/m3 is not exceeded by co-PCBs in the waste gas in addition to
      the background PCDD/F concentration. As a consequence from the new appraisals for
      toxicity equivalences (TEQ) and tolerable daily intakes (TDI) of the World Health
      Organisation the Federal Environmental Agency in Germany discusses a level of 1
      pg WHO TEQ/(kg(bw) d) as an acceptable limit value for adult's burden, taking
      into account, that this value is too much for children in the pre- and post-natal
      age and further action for PCDD/F- and co-PCB reduction is needed for the last
      sensitive group. As a summary can be reported that PCDD/F and co-PCB intakes into
      the nutrition chain could not have their origin from stationary industrial
      sources mainly. More attention should be given to more diffuse source such as
      residential combustion and others, which are more directly connected to the
      nutrition chain, like green food drying. Important effects could be expected by
      restrictions of PCDD/F impacts by regulations for control of feed, feed
      components and compounds feed for pigs and cattle.

PMID- 14659423
TI  - Estimation of the contribution of a municipal waste incinerator to the overall
      emission and human intake of PCBs in Wilrijk, Flanders.
AB  - The contribution of the emission of PCBs by a municipal waste incinerator in
      Wilrijk, a relatively industrialized district in the largest city of Flanders, to
      the total emission to air and to the total human intake was estimated. Therefore
      it was compared to the emission of PCBs by evaporation from PCB containing
      applications (transformers, capacitors, paint, ink, etc.) and to the intake of
      PCBs with food. As there was a lack of PCB data from the incinerator, the PCB
      emission concentration was estimated using three different approaches. A PCB
      measurement of the incinerator emission, performed later on, fell within the
      predicted range of 0.0004-0.005 ng TEQ/Nm3. Emission of PCBs from PCB containing
      applications and intake from food were deduced from information available on
      Flemish and European level. The results indicate a PCB contribution from the
      incinerator to local emissions between 0.3% and 3% of the emission from PCB
      containing applications and a contribution to human intake less than 6 x 10(-4)%
      of the intake from food.

PMID- 14659424
TI  - Measurement of atmospheric deposition of polychlorinated dibenzo-p-dioxins and
      dibenzofurans in the Lagoon of Venice, Italy.
AB  - Data on atmospheric fall-out of polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs) were provided by collecting bulk deposition in four
      stations inside the Lagoon of Venice. A total of 44 monthly samples was collected
      during the period July 1998-July 1999 in one site near an industrial area (Porto
      Marghera), one site in the city of Venice, and two sites in the southern- and
      northernmost ends of the Lagoon. Fluxes of PCDD/Fs were between 0.1 and 470 pg m(
      2) d(-1), corresponding to 0-9.2 pg of 2,3,7,8-TCDD equivalents (TEQ) m(-2) d(
      1), with a gradient increasing from remote to urban/industrial stations. Thus,
      annual deposition of PCDD/Fs to the Lagoon (total area=550 km2), calculated with
      various methods, turned out to be approximately 12 g, corresponding to
      approximately 400 mg TEQ. Significant differences were found among the stations,
      with a clear fingerprinting signature (PCDF/PCDD>1) of the deposition collected
      near Porto Marghera, and a reversed pattern (PCDF/PCDD<1) in the rest of the
      Lagoon, which pattern was similar to the sediments collected in the same
      locations. Lastly, the amount of bulk sigmaTEQ of all stations was compared with
      the guide values for dioxins in depositions proposed by De Fre et al.
      [Organohalogen Compounds 45 (2000) 324].

PMID- 14659425
TI  - The European dioxin air emission inventory project--final results.
AB  - Main results of the second stage of the so-called "European Dioxin Emission
      Inventory" are presented. They cover emission testing data gained from various
      facilities in the EU (among these the first emission measurements reported from
      Portugal and Greece) and some central European countries. Further, updated dioxin
      emission estimates for the most important emission sources in the 17 western
      European countries and an evaluation of the emission time trend from 1985 to 2005
      are presented. The major conclusions are, that at present, iron ore sintering is
      likely to be the most important emission source type followed by the former "No.
      1", municipal waste incineration; measurement data from a considerable number of
      installations are still missing, in particular from the metal industries in Spain
      and Italy; there still exist an unknown number of health care waste incinerators
      with flue gas PCDD/F concentrations above 100 ng I-TEQ/m3 which must be
      considered as important local sources; in general, considerable emission
      reduction has been achieved with respect to the industrial emission sources,
      whereas emissions from non-industrial sources hardly decreased; hence, in the
      near future the emissions from non-industrial sources are likely to exceed those
      from industrial installations; the goal of 90% emission reduction set in the 5th
      EU Action Programme will be achieved for some source types only.

PMID- 14659426
TI  - Perinatal dioxin exposure and later effects--a review.
AB  - Negative effects of perinatal exposure to background levels of dioxins and PCBs
      in Europe and the USA have been documented. Four facets of development are
      reviewed in this paper: 1. Brain development and thyroid hormone metabolism. 2.
      Hepatic effects. 3. Hematopoietic system effects. 4. Lung function. Effects on IQ
      and behaviour have been documented in children on both sides of the Atlantic
      Ocean. Non-dioxin-like PCBs, measured in maternal and cord blood and current
      plasma samples have been implicated. Interference with thyroid hormone metabolism
      in the mother, in the foetus and in the newborn baby could be responsible for
      these effects on brain development. During early gestation the foetus is
      completely dependent on maternal thyroxine (T4). Lower T4 levels in the mother,
      caused by dioxins and PCBs, might negatively influence (early) brain development.
      It is plausible that the intrauterine dependency on maternal T4 and the high T4
      need shortly after birth makes both these periods vulnerable for environmental
      influences. Effects of dioxin exposure on thyroid hormone metabolism have been
      described in the period shortly after birth. These effects are no longer found
      after two years of age indicating a transient effect. In animal studies, in utero
      exposure has led to effects on brain development due to abnormal induction of
      liver enzymes. This induction resulted in lower testosterone and estrogen levels,
      interfering with brain development in the vulnerable period of language
      development and the development of visuo-spatial abilities. In humans this
      developmental period occurs around the thirtieth week of pregnancy. Follow-up
      studies in puberty and adolescence of the different cohorts studied is necessary
      to evaluate these negative influences. Damaging effects on the liver found
      shortly after birth have proven to be transient. Effects on the haematopoietic
      system are clear immediately after birth, for instance on white blood cells and
      thrombocytes. An increase in middle ear infections (otitis media) in relation to
      current levels of PCBs at the age of 4 years was described in the Rotterdam
      study. Negative effects on lung function in the sense of increased obstruction
      was found after 8 years in relation to perinatal exposure to dioxins in the
      Zaandam study. This rather new finding might explain the sharp increase in lung
      problems in children in the Western world.

PMID- 14659428
TI  - Effect of backyard burning on dioxin deposition and air concentrations.
AB  - The influence from open burning of garden and household waste on locally measured
      dioxin deposition and air concentrations was evaluated in three sets of
      experiments: the combustion of garden waste in barrels and in open fires, and the
      incineration of household waste in an empty oil drum. Each set was composed of
      eight individual experiments over 4 h. Deposition gauges were located 20 m NE,
      SE, SW and NW with respect to the source and on a background location at 400 m
      SW. Air samples were taken in the plume with a medium volume sampler equipped
      with a quartz filter and a polyurethane plug. The results illustrate deposition
      increments in the wind direction at a distance of 20 m from the source of 0.8 pg
      TEQ/m2 day for garden waste and 2.5 pg TEQ/m2 day for household waste.
      Concentrations in the plume were increased by 160-580 fg TEQ/m3 over a period of
      12 and 31 h respectively. Expressed at a reference CO2 concentration of 9% this
      corresponds with a range from 0.8 to 3.6 ng TEQ/m3, which is comparable with a
      poorly controlled MSWI. Emission factors in the order of magnitude of 4.5 ng
      TEQ/kg combusted garden waste and 35 ng TEQ/kg burned municipal waste were
      determined.

PMID- 14659427
TI  - Dioxins and furans formation in pilot incineration tests of sewage sludge spiked
      with organic chlorine.
AB  - The factors affecting polychlorinated dibenzo-p-dioxins (PCDD) and
      polychlorinated dibenzofurans (PCDF) formation were studied in sewage sludge
      incineration tests carried out on a demonstrative plant. The plant includes a
      circulating fluidised bed furnace (FBF) and a rotary kiln furnace (RKF),
      operating alternatively. During the tests sewage sludge was spiked with
      chlorinated hydrocarbons and the operating parameters of the afterburning chamber
      were varied. PCDD/F were sampled in each test before the bag filter, thus
      collecting the above contaminants before abatement systems. From the tests it
      appeared that PCDD/F were always produced in more abundance in the tests carried
      out by FBF than by RKF. The higher PCDD/F concentrations in the tests by FBF were
      reached when sewage sludge was spiked with a high dosage of a surrogate organic
      mixture of chlorinated hydrocarbons and when the afterburning chamber was used
      only as transit equipment with the burner off. The distribution of the different
      PCDD/F homologues was compared. P5CDFs were generally the prevalent fraction,
      with very few exceptions for the tests by RKF at high temperature of the
      afterburning chamber. As for FBF tests, it was found that the PCDD/F homologue
      profile depends on the afterburning chamber temperature.

PMID- 14659429
TI  - Catalytic NOx reduction with simultaneous dioxin and furan oxidation.
AB  - The engineering, construction, performance and running costs of a catalytic flue
      gas cleaning component in the low dust area of a municipal waste incinerator is
      discussed. For this purpose, the case study of a Flemish incineration plant is
      presented, covering the history, the design procedure of the catalyst, relevant
      process data and the financial aspects. A reliable PCDD/F-destruction by means of
      oxidation by the catalyst to typical values of 0.001 ng TEQ/Nm3 has been
      demonstrated. At the same time, NOx- and CO-emissions are reduced by 90% and 20%
      to about 50 mg/Nm3 and below 10 mg/Nm3, respectively.

PMID- 14659430
TI  - Affinity purification of recombinant protein-tyrosine phosphatase 1B using a
      highly selective inhibitor.
AB  - Our structure-based drug discovery program within the field of protein-tyrosine
      phosphatases (PTPs) demands delivery of significant amounts of protein with
      extraordinary purity specifications over prolonged time periods. Hence,
      replacement of classical, multi-step, low-yield protein purifications with
      efficient affinity techniques would be desirable. For this purpose, the highly
      selective PTP1B inhibitor 2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3
      c]pyridine-3-carboxylic acid (OTP) was coupled to epoxy-activated Sepharose 6B
      (OTP Sepharose) and used for one-step affinity purification of tag-free PTP1B.
      The elution was performed with a combined pH and salt gradient. Importantly,
      since OTP Sepharose binds PTP1B with an intact active site only, the method
      ensures that the purified enzyme is fully active, a feature that might be
      particularly important in PTP research.

PMID- 14659431
TI  - Column-switching technique for the sensitive determination of ertapenem in human
      cerebrospinal fluid using liquid chromatography and ultraviolet absorbance
      detection.
AB  - A sensitive reversed-phase high-performance liquid chromatographic (RP-HPLC)
      assay with on-line extraction was developed for quantifying ertapenem in human
      cerebrospinal fluid (CSF). This assay is at least five times more sensitive than
      previously published ertapenem methods with a lower limit of quantitation at
      0.025 microg/ml. In this assay, a CSF sample is extracted on-line using a RP
      extraction column and an aqueous acidic mobile phase (0.1% formic acid) to wash
      away polar endogenous materials, while ertapenem is retained on the column.
      Ertapenem is then back-flushed off the extraction column and directed to a RP
      analytical column using an acidic mobile phase with an organic modifier
      (acetonitrile/0.1% formic acid, 15:85 (v/v)) and detected using UV absorbance.
      The acidic mobile phase provided a sharper chromatographic peak and on-line
      extraction allowed large injection volumes (> or = 150 microl) of buffered CSF to
      be injected without compromising column integrity. These assay conditions were
      necessary to quantify ertapenem at levels expected to be found in human CSF (<
      0.05 microg/ml). The method was successfully validated and implemented for a
      clinical study: intraday precision and accuracy of the CSF assay for calibration
      standards (0.025-10 microg/ml) and quality control samples (0.1, 0.5, and 2.5
      microg/ml) were < 6.2% coefficient of variation and 96.8-104.0% of nominal
      concentration, respectively.

PMID- 14659432
TI  - Liquid chromatographic assays for DE-310, a novel camptothecin analog, and two
      major enzymatic products in human matrices.
AB  - Assays were developed for determination of DE-310, a carboxymethyldextran
      polyalcohol conjugate of the topoisomerase I inhibitor DX-8951 (exatecan) and two
      enzymatic products (i.e. glycyl-DX-8951 and unconjugated DX-8951) in human whole
      blood, erythrocytes and saliva. Sample pretreatment involved a single protein
      precipitation step, followed by a thermolysin-mediated deconjugation for the
      parent molecule. Separation of the compounds was achieved on an Inertsil ODS-80A
      column (150 mm x 4.6 mm i.d.; 5 microm PS), using isocratic elution. The column
      effluent was monitored at excitation and emission wavelengths of 375 and 445 nm,
      respectively. Validation results indicated that the methods are accurate and
      precise at lower limits of quantitation of 0.5-6.9 ng/ml. The methods were used
      to study the blood distribution and salivary concentrations in patients receiving
      DE-310.

PMID- 14659433
TI  - Liquid chromatographic method for detection and quantitation of STI-571 and its
      main metabolite N-desmethyl-STI in plasma, urine, cerebrospinal fluid, culture
      medium and cell preparations.
AB  - An isocratic online-enrichment HPLC-assay was developed allowing for the simple
      and fast separation and quantitation of STI-571 and its main metabolite N
      desmethyl-STI (N-DesM-STI) in plasma, urine, cerebrospinal fluid (CSF), culture
      media and cell preparations in various concentrations using UV-detection at 260
      nm. The analytical procedure consists of an online concentration of STI-571 and N
      DesM-STI in the HPLC system followed by the elution on a ZirChrom-PBD analytical
      column. Time of analysis is 40 min including the enrichment time of 5 min. The
      detection limit is 10 ng/ml in plasma, CSF, culture medium (RPMI) and 25 ng/ml in
      urine for both STI-571 and N-DesM-STI. The intra-day precision, as expressed by
      the coefficient of variation (CV), in plasma samples ranges between 1.74 and
      8.60% for STI-571 and 1.45 and 8.87% for N-DesM-STI. The corresponding values for
      urine measurements are 2.17-7.54% (STI-571) and 1.31-9.51% (N-DesM-STI). The
      inter-day precision analyzed over a 7-month time period was 8.31% (STI-571) or
      6.88% (N-DesM-STI) and 16.45% (STI-571) or 14.83% (N-DesM-STI) for a
      concentration of 1000 ng/ml in plasma and 750 ng/ml in urine, respectively.
      Moreover, we demonstrate that with an alternative, but more time and labor
      consuming sample preparation and the implementation of electrochemical detection,
      a detection limit < 10 ng/ml can be achieved. The method described was used to
      perform pharmacokinetic measurements of STI-571 and N-desmethyl-STI in patient
      samples and for kinetic measurements of intracellular STI-571 and N-DesM-STI
      following in vitro incubation.

PMID- 14659434
TI  - Gas chromatography-isotope dilution mass spectrometry preceded by liquid-liquid
      extraction and chemical derivatization for the determination of ketamine and
      norketamine in urine.
AB  - An analytical scheme using gas chromatography (GC)-isotope dilution mass
      spectrometry (MS) assisted by precedent liquid-liquid extraction (LLE) and
      chemical derivatization (ChD) is described for the simultaneous determination of
      ketamine (KT) and its major metabolite, norketamine (NK), in urine. The
      simultaneous ChD of the two analytes, one primary amine and one secondary amine,
      with pentafluorobenzoyl chloride (PFBC) has not only enhanced their instrumental
      responses and mass-spectrum uniqueness but also afforded more proper yet easier
      selection of qualifier and quantifier ions and hence achieved more evidential
      identification and quantitation. Thus, the regression calibration curves for KT
      and NK in urine are linear within 100-5000 ng/ml, with correlation coefficients
      typically exceeding 0.99 and NK curves exclusively showing larger slopes than KT
      curves. The method limits of detection (LODs) determined by two definitions for
      KT and NK range from 3 to 75 ng/ml, and limits of quantitation (LOQs) from 9 to
      100 ng/ml. The mean recoveries (N = 3) calculated for the LLE/ChD of KT and NK
      from 50 and 100 microl, respectively, of a 100 microg/ml urinary spike vary from
      71.0 to 97.8%, with NK consistently giving better recoveries than KT. The
      precisions (N = 3) calculated for the total analyses of four real-case samples
      are typically below 12.3%. GC-MS operated in the positive ion chemical ionization
      (PCI) mode can offer both qualitative and quantitative information complementary
      to those given by the EI mode. The proposed scheme is simple, effective,
      reliable, and robust. It may serve as a confirmatory protocol for forensic urine
      drug testing.

PMID- 14659435
TI  - Liquid chromatographic-tandem mass spectrometric assay for the simultaneous
      determination of didanosine and stavudine in human plasma, bronchoalveolar lavage
      fluid, alveolar cells, peripheral blood mononuclear cells, seminal plasma,
      cerebrospinal fluid and tonsil tissue.
AB  - We have developed a sensitive, high-pressure liquid chromatographic-tandem mass
      spectrometric (LC/MS/MS) method for the simultaneous determination of didanosine
      (ddI) and stavudine (d4T) in human plasma, bronchoalveolar lavage fluid (BALF),
      alveolar cells (AC), peripheral blood mononuclear cells (PBMC), seminal plasma,
      cerebrospinal fluid (CSF), and tonsil tissue. Plasma, AC, PBMC and CSF were run
      with an isocratic HPLC method, while BALF supernatant, semen, and tonsil tissue
      utilized a gradient elution. Samples were prepared by solid phase extraction.
      Detection was by electrospray positive ionization with multiple reaction
      monitoring mode. The lower limits of quantitation for both ddI and d4T were 2.0
      ng/ml in plasma; 0.5 ng/ml in CSF; 0.4 ng/ml in AC, PBMC, and BALF; 1.0 ng/ml in
      seminal plasma; and 0.01 ng/mg in tonsil tissue.

PMID- 14659436
TI  - Development of a bioanalytical liquid chromatography method for quantitation of 9
      nitrocamptothecin in human plasma.
AB  - 9-Nitrocamptothecin (9-NC) is an orally administered camptothecin (CPT) that is
      under evaluation in clinical trials. This compound is not fluorescent, which has
      hampered development of a sensitive high-performance liquid chromatographic (LC)
      assay for measurement of drug concentrations in clinical trials. We now report
      development of an assay that involves reduction of 9-NC to the fluorescent
      compound 9-aminocamptothecin (9-AC). The method is based on enzymatic reduction
      of 9-NC using bovine liver S-9 fraction. This method is validated to quantitate 9
      NC and 9-AC in patient samples, and yields results comparable to those obtained
      with an LC/MS method.

PMID- 14659437
TI  - Effect of different matrices on physiological amino acids analysis by liquid
      chromatography: evaluation and correction of the matrix effect.
AB  - Free amino acids in plasma, muscle and liver tissues were determined using the
      Pico-Tag method which involves HPLC and pre-column derivatization. A study of the
      accuracy in the determination is carried out by means of external calibration,
      standard-added calibration, Youden calibration and analyte recovery. It is
      conclusively shown that the method is affected by a proportional systematic error
      due to matrix effects, but not by a constant one. A new function named matrix
      corrected calibration is proposed to correct for proportional bias when free
      analyte matrices for matrix-matched addition is unavailable.

PMID- 14659438
TI  - Simple and sensitive method for quantification of fludarabine triphosphate
      intracellular concentration in leukemic cells using isocratic liquid
      chromatography.
AB  - A simple, isocratic HPLC method was newly developed for quantitating
      intracellular fludarabine triphosphate (F-ara-ATP). Samples (500 microl) were
      injected onto an anion-exchange column and eluted isocratically with phosphate
      acetonitrile buffer (flow rate: 0.7 ml/min) at an ambient temperature. F-ara-ATP
      was quantitated according to its peak area at the absorbance of 261 nm. The
      standard curve was linear with minimal within-day and inter-day variability. The
      low and high quantification limits were 50 pmol and 20 nmol, respectively. The
      method was capable of measuring F-ara-ATP generated in cultured leukemic cells in
      vitro. Thus, our method will be useful because of its sensitivity and simplicity
      as well as applicability to biological materials.

PMID- 14659439
TI  - One-step, non-denaturing purification method of carp (Cyprinus carpio)
      vitellogenin.
AB  - A new single-step purification procedure was developed to purify carp (Cyprinus
      carpio) vitellogenin (VTG), from estradiol-treated carp plasma. This method was
      performed by high performance liquid weak anion-exchange chromatography, using a
      discontinuous elution gradient of NaCl (0-0.5 M, steps of 12.5 mM/4 min). SDS and
      native-PAGE analysis, of treated-fish plasma and purified solution, showed the
      appearance of a 370 kDa phospholipoprotein, composed of two 130 kDa monomers,
      with all VTG characteristics. The sequencing of a 130 kDa monomer confirmed that
      it was carp VTG. Consequently, this procedure is a rapid method, permitting high
      quantities of non-denatured carp VTG to be obtained.

PMID- 14659440
TI  - Quantification of F-ring isoprostane-like compounds (F4-neuroprostanes) derived
      from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass
      spectrometric assay.
AB  - Lipid peroxidation has been implicated in the pathophysiological sequelae of
      human neurodegenerative disorders. It is recognized that quantification of lipid
      peroxidation is best assessed in vivo by measuring a series of prostaglandin (PG)
      F2-like compounds termed F2-isoprostanes (IsoPs) in tissues in which arachidonic
      acid is abundant. Unlike other organs, the major polyunsaturated fatty acid
      (PUFA) in the brain is docosahexaenoic acid (DHA, C22:6 omega-6), and this fatty
      acid is particularly enriched in neurons. We have previously reported that DHA
      undergoes oxidation in vitro and in vivo resulting in the formation of a series
      of F2-IsoP-like compounds termed F4-neuroprostanes (F4-NPs). We recently
      chemically synthesized one F4-NP, 17-F4c-NP, converted it to an 18O-labeled
      derivative, and utilized it as an internal standard to develop an assay to
      quantify endogenous production of F4-NPs by gas chromatography (GC)/negative ion
      chemical ionization (NICI) mass spectrometry (MS). The assay is highly precise
      and accurate. The lower limit of sensitivity is approximately 10 pg. Levels of F4
      NPs in brain tissue from rodents were 8.7 +/- 2.0 ng/g wet weight (mean +/-
      S.D.). Levels of the F4-NPs in brains from normal humans were found to be 4.9 +/-
      0.6 ng/g (mean +/- S.D.) and were 2.1-fold higher in affected regions of brains
      from humans with Alzheimer's disease (P = 0.02). Thus, this assay provides a
      sensitive and accurate method to assess oxidation of DHA in animal and human
      tissues and will allow for the further elucidation of the role of oxidative
      injury to the central nervous system in association with human neurodegenerative
      disorders.

PMID- 14659441
TI  - Determination of glimepiride in human plasma by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - A sensitive and specific high-performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry (HPLC-ESI-MS-MS) method has been developed at
      our center for the determination of glimepiride in human plasma. After the
      addition of the internal standard, plasma samples were extracted by liquid-liquid
      extraction technique using diethyl ether. The compounds were separated on a
      prepacked C18 column using a mixture of acetonitrile, methanol and ammonium
      acetate buffer as mobile phase. A Finnigan LCQDUO ion trap mass spectrometer
      connected to an Alliance Waters HPLC was used to develop and validate the method.
      The analytical method was validated according to the FDA bioanalytical method
      validation guidance. The results were within the accepted criteria as stated in
      the aforementioned guidance. The method was proved to be sensitive and specific
      by testing six different plasma batches. Linearity was established for the range
      of concentrations 5.0-500.0 ng/ml with a coefficient of determination (r2) of
      0.9998. Accuracy for glimepiride ranged from 100.58 to 104.48% at low, mid and
      high levels. The intra-day precision was better than 12.24%. The lower limit of
      quantitation (LLOQ) was identifiable and reproducible at 5.0 ng/ml with a
      precision of 7.96%. The proposed method enables the unambiguous identification
      and quantitation of glimepiride for pharmacokinetic, bioavailability or
      bioequivalence studies.

PMID- 14659442
TI  - Determination of menthol in plasma and urine of rats and humans by headspace
      solid phase microextraction and gas chromatography--mass spectrometry.
AB  - A method for the determination of menthol and menthol glucuronide (M-G) after
      enzymatic hydrolysis in plasma and urine of rats and humans was developed using
      headspace solid phase microextraction and gas chromatography-mass spectrometry in
      the selected ion monitoring mode (HS-SPME/GC-MS). The assay linearity for plasma
      ranged from 5 to 1000 ng/ml. The limit of quantification (LOQ) in plasma was 5
      ng/ml. The intra- and inter-day precision for menthol and M-G were < or = 18.1%
      R.S.D. at the LOQ and < or = 4.0% at higher concentrations. Menthol and M-G were
      determined in rat and human plasma and urine after administration of menthol.

PMID- 14659443
TI  - Stir bar sorptive extraction and thermal desorption-gas chromatography-mass
      spectrometry for the measurement of 4-nonylphenol and 4-tert-octylphenol in human
      biological samples.
AB  - Alkylphenols, 4-nonylphenol (NP) and 4-tert-octylphenol (OP), in human urine and
      plasma samples were analyzed using stir bar sorptive extraction (SBSE) in
      combination with thermal desorption-gas chromatography-mass spectrometry (TD-GC
      MS). The method involved correction by stable isotopically labeled surrogate
      standards, 4-(1-methyl)octylphenol-d5 (m-OP-d5) and deuterium 4-tert-octylphenol
      (OP-d). A biological sample was extracted for 60 min at room temperature (25
      degrees C) using a stir bar coated with a 500 microm thick polydimethylsiloxane
      (PDMS) layer. Then, the stir bar was analyzed by TD-GC-MS in the selected ion
      monitoring (SIM) mode without any derivatization step. The average recoveries in
      human urine and plasma samples spiked with NP and OP at levels of 0.5 and 10 ng
      ml-1 were between 95.8 and 99.8% with correction using the added surrogate
      standards. The limits of quantitation were 0.2 ng ml-1 for NP and 0.02 ng ml-1
      for OP. We measured the background levels of NP and OP in five human urine and
      three human plasma samples from healthy volunteers. NP and OP were not detected
      in all human urine samples (N.D. < 0.2 ng ml-1 for NP, and N.D. < 0.02 ng ml-1
      for OP). However, 0.2-0.3 ng ml-1 for NP and 0.1-0.2 ng ml-1 for OP in human
      plasma samples were observed by this method.

PMID- 14659444
TI  - Validation of non-aqueous capillary electrophoresis for simultaneous
      determination of four tricyclic antidepressants in pharmaceutical formulations
      and plasma samples.
AB  - We present the validation of a method using non-aqueous capillary electrophoresis
      (NACE) for quantitative analysis of four tricyclic antidepressants (TADs) in
      pharmaceutical formulations and plasma. The method presented high resolution
      allowing the separation of the TADs in 4.3 min at optimized conditions: 50 mM
      ammonium acetate, 1 M acetic acid in acetonitrile, capillary with 48 cm in
      length, 40 cm to the detector, and voltage of 30 kV. Acceptable precision
      (relative standard deviation R.S.D.14.1% from plasma samples) and linearity were
      achieved using the internal standard (IS) method. The limits of quantification
      determined for plasma, after liquid-liquid extraction (LLE), were between 30 and
      50 ng ml-1. These values are beyond the plasmatic therapeutic concentration. Our
      results were found comparable or better than those described in the literature
      for high performance liquid chromatography (HPLC)-based methods.

PMID- 14659445
TI  - Determination of disodium clodronate in human plasma and urine using gas
      chromatography-nitrogen-phosphorous detections: validation and application in
      pharmacokinetic study.
AB  - We present a specific method for the determination of disodium clodronate in
      human plasma and urine using a gas-chromatographic system with nitrogen
      phosphorus detector (NPD). The compound was extracted from plasma and urine
      samples by an anion-exchange resin and derivatizated with
      bistrimethylsilyltrifluoroacetamide (BSTFA). Sodium bromobisphosphonate was used
      as internal standard. The calibration curves were linear in both plasma and
      urine, with a regression coefficient r > 0.9975 in plasma and r > 0.9977 in
      urine. The limit of quantitation was 0.3 microg/ml in plasma and 0.5 microg/ml in
      urine. The method was validated by intra-day assays at three concentration
      levels. During the study we carried out inter-day assays to confirm the
      feasibility of the method. The precision in plasma at 0.5, 15, and 45 microg/ml
      was 12.4, 0.2, and 6.5% (n = 40), respectively; in urine at 0.8, 8, and 40
      microg/ml it was 8.6, 6.4, and 9.3% (n = 40), respectively. The method was
      accurate and reproducible, and was successfully applied to determine the
      pharmacokinetic parameters of clodronate in healthy volunteers after intravenous
      infusion and intramuscular injection of 200 mg of the compound. The Cmax after
      intravenous infusion and intramuscular injection was 16.1 and 12.8 microg/ml,
      respectively. AUC(0-48 h) after infusion administration and intramuscular
      injection was 44.2 +/- 18.0 and 47.5 +/- 12.4 h microg/ml, respectively. The
      elimination half-life in both administrations was 6.31 +/- 2.7 h.

PMID- 14659446
TI  - Validation of a simple liquid chromatography-tandem mass spectrometric method for
      the determination of propiverine hydrochloride and its N-oxide metabolite in
      human plasma.
AB  - A simple high-performance liquid chromatography (HPLC)-tandem mass spectrometric
      method has been developed for determination of propiverine hydrochloride and its
      metabolite, propiverine N-oxide (M-1) in human plasma using stable isotopes,
      propiverine hydrochloride-d10 and M-1-d10, as internal standards. The analytes
      were extracted with dichloromethane from 0.2 ml of plasma in neutral condition
      (pH 7.0) and separated by HPLC on a C18 reversed-phase column using methanol-1%
      acetic acid (50:50) as a mobile phase, and detected using positive electrospray
      ionization in selected reaction monitoring (SRM) mode. The method was validated
      over a concentration range of 2-500 ng/ml for propiverine hydrochloride and 4
      1000 ng/ml for M-1 using 0.2 ml of human plasma per assay. The method developed
      was successfully applied to analysis of propiverine hydrochloride and M-1 in
      clinical studies.

PMID- 14659447
TI  - Improved liquid chromatographic method for mitoxantrone quantification in mouse
      plasma and tissues to study the pharmacokinetics of a liposome entrapped
      mitoxantrone formulation.
AB  - A simple, rapid HPLC method for quantification of mitoxantrone in mouse plasma
      and tissue homogenates in the presence of a liposome entrapped mitoxantrone
      formulation (LEM-ETU) is described. Sample preparation is achieved by protein
      precipitation of 100 microl plasma or 200 microl tissue homogenate with an equal
      volume of methanol containing 0.5 M hydrochloric acid:acetonitrile (90:10, v/v).
      Ametantrone is used as the internal standard (i.s.). Mitoxantrone and i.s. are
      separated on a C18 reversed phase HPLC column, and quantified by their absorbance
      at 655 nm. In plasma, the standard curve is linear from 5 to 1000 ng/ml, and the
      precision (%CV) and accuracy (percentage of nominal concentration) are within
      10%. In mouse tissue (heart, kidney, liver, lung, and spleen) homogenates (5%,
      w/v), the standard curve is linear from 25 to 2000 ng/ml, with acceptable
      precision and accuracy. The method was used to successfully quantify mitoxantrone
      in mouse plasma and tissue samples to support a pharmacokinetic study of LEM-ETU
      in mice.

PMID- 14659448
TI  - Quantification of free mycophenolic acid and its glucuronide metabolite in human
      plasma by liquid-chromatography using mass spectrometric and ultraviolet
      absorbance detection.
AB  - The immunosuppressant drug mycophenolic acid (MPA) and its major metabolite,
      mycophenolic acid glucuronide (MPAG), are highly bound to albumin. An HPLC-tandem
      MS (HPLC/MS/MS) and an HPLC-UV assay were developed to measure free (unbound)
      concentrations of MPA and MPAG, respectively. Ultrafiltrate was prepared from
      plasma (500 microl) by ultrafiltration at 3000 x g for 20 min (20 degrees C).
      Both MPA and MPAG were isolated from ultrafiltrate (100 microl) by acidification
      and C18 solid-phase extraction. Free MPA was measured by electrospray tandem mass
      spectrometry using selected reactant monitoring (MPA: m/z 338.2--> 206.9) in
      positive ionisation mode. Chromatography was performed on a PFPP column (50 mm x
      2 mm, 5 microm). Total analysis time was 7 min. The assay was linear over the
      range 1-200 microg/l with a limit of quantification of 1 microg/l. The inter-day
      accuracy and imprecision of quality controls (7.5, 40, 150 microg/l) were 94-99%
      and < 7%, respectively. Free MPAG was chromatographed on a C18 Nova-Pak column
      (150 mm x 3.9 mm, 5 microm) using a binary gradient over 20 min. The eluent was
      monitored at 254 nm. The assay was linear over the range 1-50 mg/l with the limit
      of quantification at 2.5 mg/l. The inter-day accuracy and imprecision of quality
      controls (5, 20, 45 mg/l) was 101-107% and < 8% (n = 4), respectively. For both
      methods no interfering substances were found in ultrafiltrate from patients not
      receiving MPA. The methods described have a suitable dynamic linear range to
      facilitate the investigation of free MPA and MPAG pharmacokinetics in transplant
      patients. Further, this is the first reported HPLC-UV method to determine free
      MPAG concentrations.

PMID- 14659449
TI  - Determination of levofloxacin in plasma, bronchoalveolar lavage and bone tissues
      by high-performance liquid chromatography with ultraviolet detection using a
      fully automated extraction method.
AB  - The aim of this study was to develop a specific and sensitive high-performance
      liquid chromatographic (HPLC) assay for the determination of levofloxacin in
      human plasma, bronchoalveolar lavage and bone tissues. The sample extraction was
      based on a fully automated liquid-solid extraction with an OASIS cartridge. The
      method used ultraviolet detection set at a wavelength of 299 nm and a separation
      with a Supelcosil ABZ+ column. The assay has been found linear over the
      concentration range 0.25-25 microg/ml for levofloxacin in plasma, 1-6 microg/ml
      in bronchoalveolar lavage and 0.5-10 microg/g for bone tissues and it provided
      good validation data for accuracy and precision. The assay will be applied to
      determine the penetration of levofloxacin in human bronchoalveolar lavage (BAL)
      and bone tissues during pharmacokinetic steady state.

PMID- 14659450
TI  - Selective and sensitive liquid chromatographic assay of amodiaquine and
      desethylamodiaquine in whole blood spotted on filter paper.
AB  - We have developed a sensitive, selective and reproducible reversed-phase HPLC
      method with ultraviolet detection (340 nm) for the simultaneous quantification of
      amodiaquine (AQ) and its major metabolite, desethylamodiaquine (AQm) in a small
      volume (200 microl) of whole blood spotted on filter paper. The method involves
      liquid-liquid extraction with diethyl ether followed by elution from a reversed
      phase phenyl column with an acidic (pH 2.8) mobile phase (25 mM KH2PO4-methanol;
      80:20% (v/v) +1% (v/v) triethylamine). Calibration curves in spiked whole blood
      were linear from 100-2500 ng/ml (r2 > or = 0.99) for AQ and 200-2500 ng/ml (r2 >
      or = 0.99) for AQm. The limit of detection was 5 ng for AQ and 10 ng for AQm. The
      relative recovery at 150 ng/ml of AQ (n = 6) was 84.0% and at 300 ng/ml of AQm
      the relative recovery was 74.3%. The intra-assay coefficients of variation at
      150, 600 and 2250 ng/ml of AQ and 300, 600 and 2250 ng/ml of AQm were 7.7, 8.9
      and 6.2% (AQ) and 10.1, 5.4 and 3.9% (AQm), respectively. The inter-assay
      coefficient of variation at 150, 600 and 2250 ng/ml of AQ and 300, 600 and 2250
      ng/ml of AQm were 5.2, 8.1 and 6.9% (AQ) and 3.3, 2.3 and 4.6% (AQm). There was
      no interference from other commonly used antimalarial and antipyretic drugs
      (chloroquine, quinine, sulfadoxine, pyrimethamine, artesunate, acetaminophen and
      salicylate). The method is particularly suitable for pharmacokinetic studies in
      settings where facilities for storing blood/plasma samples are not available.

PMID- 14659451
TI  - Determination of the basicity of Mannich ketones by capillary electrophoresis.
AB  - Capillary electrophoretic (CE) method to characterise Mannich ketones (MKs)
      containing morpholine moiety was developed. Basicity (pKa,exp) of the MKs was
      characterised by measured data derived from the electrophoretic mobility values
      obtained in the CE separation. The MKs were found to be weaker bases than the
      parent morpholine molecule itself and the experimentally determined basicity
      values proved to be dependent on the chemical structure of the MKs. Since the
      basicity of the MKs has an influence on their reactivity and biological activity
      it seems to be useful to determine experimentally the pKa,exp values of the newly
      synthesised compounds to support rational drug design or screening of the
      molecule libraries.

PMID- 14659452
TI  - Nitric oxide inhibits mitochondrial monoamine oxidase activity and decreases
      outer mitochondria membrane fluidity.
AB  - The recent finding that mitochondria contain a nitric oxide (NO) synthase
      suggests that this compound is involved in the regulation of various
      mitochondrial functions. Monoamine oxidase (MAO) is embedded in the outer
      mitochondrial membrane. NO modulates membrane fluidity. Thus, the aim of the
      present work was to study the effect of NO on mitochondrial MAO activity and
      membrane fluidity. An outer mitochondrial membrane fraction (OMMF) was obtained
      from rat liver. OMMF was incubated with various concentrations of S-nitroso-N
      acetylpenicillamine (SNAP), a NO donor. MAO activity and fluidity were measured
      by a spectrophotometric assay and by the polarization of fluorescence technique,
      respectively. It was found that small concentrations of SNAP (0.4-40 microM) were
      capable of inhibiting MAO activity but unable to decrease fluidity significantly.
      In contrast, larger amounts of SNAP (40-300 microM) effectively decreased
      membrane fluidity, but were not able to further decrease MAO activity. This
      information suggests that mitochondrial MAO and membrane fluidity possess
      different sensitivity to the effect of NO. Unfortunately, the mechanism by which
      NO inhibits MAO remains unknown at present. However, it seems likely that the
      effect of NO on MAO activity is by a direct interaction of the compound or a
      metabolite to the protein.

PMID- 14659453
TI  - Effects of 9-cis- and all-trans-retinoic acids on blood glucose homeostasis in
      the fiddler crab, Uca pugilator.
AB  - 9-cis-Retinoic acid (9CRA) and all-trans-retinoic acid (ATRA) are known to be
      involved in the regulation of glucose homeostasis in vertebrates by inducing
      insulin release and expression of glucose transporter proteins. In view of the
      fact that both 9CRA and ATRA are endogenous to the fiddler crab, Uca pugilator,
      that a retinoid X receptor exists in this fiddler crab and that activities of
      insulin-like and insulin-like growth factor-like peptides have been reported for
      crustaceans, we investigated whether 9CRA and ATRA also play a role in glucose
      homeostasis in U. pugilator. Neither 9CRA nor ATRA was found to produce
      hypoglycemic effects at a dose of 10 microg/g live mass. However, 9CRA, but not
      ATRA, induced hyperglycemia. Such 9CRA-induced hyperglycemia was apparently
      mediated by the eyestalk hormone CHH since injection of 9CRA into eyestalk
      ablated crabs did not result in hyperglycemia. ATRA was found to have an
      inhibitory effect on the recovery of blood glucose concentration following ATRA
      administration. Discussion on the possible mechanisms for the actions of 9CRA and
      ATRA was presented.

PMID- 14659454
TI  - Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat
      pancreas.
AB  - The aim of this study was to analyze the effect of the flavonoid silymarin, a
      free radical scavenger that prevents lipoperoxidation, on the pancreatic activity
      of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT)
      in rats with alloxan-induced diabetes mellitus. Alloxan intoxicated rats were
      treated with silymarin in two manners, simultaneously (four or eight doses) or 20
      days after alloxan administration for 9 weeks. Alloxan elicited a transient
      increase in the activity of the three enzymes, which decreased after 5 days of
      treatment. On its own, silymarin significantly increased the activity of these
      enzymes. Simultaneous treatment with alloxan and silymarin also induced an
      increment in the activity of the enzymes followed by a delayed decrease (four
      doses). However, a longer treatment with silymarin (eight doses) induced a more
      sustained effect. Interestingly, silymarin treatment recovered to control values
      for the activity of the three-antioxidant enzymes that were significantly
      diminished after 20 days of alloxan administration. It is suggested that the
      protective effect of silymarin on pancreatic damage induced by alloxan may be due
      to an increase in the activity of antioxidant enzymes that, in addition to the
      glutathione system, constitute the more important defense mechanisms against
      damage by free radicals.

PMID- 14659455
TI  - Cellular localization of calcium, heavy metals, and metallothionein in lobster
      (Homarus americanus) hepatopancreas.
AB  - This investigation combines confocal microscopy with the cation-specific
      fluorescent dyes Fluo-3 and BTC-5N to localize calcium and heavy metals along the
      length of intact lobster (Homarus americanus) hepatopancreatic tubules and
      isolated cells. A metallothionein-specific antibody, developed in mollusks with
      cross-reactivity in crustaceans, showed the tissue-specific occurrence of this
      metal-binding protein in several organ systems in lobster and in single cell
      types isolated from lobster hepatopancreas. Individual lobster hepatopancreatic
      epithelial cell types were separated into pure single cell type suspensions for
      confocal and antibody experiments. Intact hepatopancreatic tubules showed high
      concentrations of both calcium and heavy metals at the distal tips of tubules
      where mitotic stem cells (E-cells) are localized. In addition, a concentrated
      distribution of calcium signal within isolated single premolt E-cells in solution
      was disclosed that might suggest an endoplasmic reticulum compartmentation of
      this cation within these stem cells. Both E- and R-cells showed significantly (P
      < 0.05) greater intracellular calcium concentrations in premolt than intermolt,
      suggesting the accumulation of this cation in these cells prior to the molt.
      Antibody studies with lobster tissues indicated that the hepatopancreas possessed
      5-10 times the metallothionein concentration as other lobster organ systems and
      that isolated E-cells from the hepatopancreas displayed more than twice the
      binding protein concentrations of other cells of this organ or those of blood
      cells. These results suggest that crustacean hepatopancreatic stem cells (E
      cells) and R-cells play significant roles in calcium and heavy metal homeostasis
      in this tissue. Interactions between the four hepatopancreatic cell types in this
      regulatory activity remain to be elucidated.

PMID- 14659456
TI  - Effect of lead acetate on the in vitro engulfment and killing capability of toad
      (Bufo arenarum) neutrophils.
AB  - Lead is an element of risk for the environment and human health and has harmful
      effects that may exceed those of other inorganic toxicants. The immune system is
      one of the targets of lead. Its immunomodulatory actions depend on the level of
      exposure, and it has been demonstrated that environmental amounts of the metal
      alter immune function. Very little information is available regarding the effect
      of the metal on different aspects of the immune system of lower vertebrates, in
      particular of amphibians. The aim of this study was to investigate the effect of
      sublethal lead (as acetate) on the function of polymorphonuclear cells of Bufo
      arenarum. The results revealed that phagocytic and lytic functions of the
      adherent blood cells collected from sublethal lead-injected toads and incubated
      with suspensions of Candida pseudotropicalis were affected negatively. The
      decrease of the phagocytic activity was correlated with increased blood lead
      levels (P < 0.0001). Additional information referred to the total and
      differential leukocyte counts was presented; the only difference found was in the
      number of blast-like cells that resulted augmented in the samples of lead
      injected toads. It was concluded that the evaluation of these parameters might be
      a reliable tool for the biological monitoring of the immune status of amphibians.

PMID- 14659457
TI  - EROD activity in gill filaments of anadromous and marine fish as a biomarker of
      dioxin-like pollutants.
AB  - The applicability of a gill filament-based ethoxyresorufin O-deethylase (EROD)
      assay, originally developed in rainbow trout, was examined in Atlantic salmon
      (Salmo salar), Arctic charr (Salvelinus alpinus), Atlantic cod (Gadus morhua),
      saithe (Pollachius virens) and spotted wolffish (Anarhichas minor). All species
      but spotted wolffish showed strong EROD induction in tip pieces of gill filaments
      following 48 h of exposure to waterborne beta-naphthoflavone. Atlantic salmon
      parr, smolts held in freshwater and smolts transferred to seawater showed EROD
      induction of similar magnitude. Arctic charr, differing 11-fold in body weight,
      showed similar EROD activities as expressed per gill filament tip. Laboratory
      exposure of saithe to water and sediments collected at polluted sites, resulted
      in strong EROD induction. In conclusion, the gill filament assay seems useful for
      monitoring exposure to aryl hydrocarbon receptor agonists in various species.
      Furthermore, smoltification status, water salinity and body size proved to have
      minor influence on gill filament EROD activity. However, the results in spotted
      wolffish show that some species may be less suitable for monitoring using the
      gill assay. Assessment of gill filament EROD activity in fish exposed to polluted
      water and sediments in the laboratory proved to be an easy and cost-effective way
      to survey pollution with dioxin-like chemicals.

PMID- 14659458
TI  - Cannabinoid CB1 receptor activation does not prevent the toxicity of glutamate
      towards embryonic chick telencephalon primary cultures.
AB  - Cannabinoids, as a result of their ability to activate cannabinoid CB1 receptors,
      have been shown to possess neuroprotective properties in vivo. In vitro studies
      into neuroprotective effects mediated by CB1 receptors have in general used
      primary neuronal cultures derived from embryonic rodents. In the present study,
      we have investigated whether embryonic chick telencephalon primary cultures in
      serum-free medium are a useful alternative for such in vitro studies. The CB
      agonist CP 55940 reduced the cAMP response to 5 microM forskolin by 40 and 50% at
      concentrations of 3 nM and 30 nM, respectively. This reduction was blocked by the
      CB1 receptor antagonist AM251, indicating the presence of functional CB1
      receptors in the cultures. Incubation of the cultures with glutamate (100 microM
      or 1 mM) for 1 h followed by medium change and incubation for 24 h produced a
      release of the cytoplasmic enzyme lactate dehydrogenase into the medium. This
      release was prevented by MK-801 confirming the central role of NMDA receptors in
      the glutamate toxicity. However, 3-30 nM CP 55940 did not produce any
      neuroprotection in this model regardless as to whether dibutyryl cyclic AMP was
      added to the culture medium. The endocannabinoid anandamide was also without
      effect when added either per se or together with the related N-acyl ethanolamines
      palmitoylethanolamide, oleoylethanolamide and stearoylethanolamide (at relative
      concentrations matching those seen in rat brain after excitotoxic insult). It is
      concluded that embryonic chick neurons in primary serum-free culture are not a
      useful model for the study of neuroprotective effects mediated by CB1 receptors
      in vitro.

PMID- 14659459
TI  - Acclimation of Daphnia magna to environmentally realistic copper concentrations.
AB  - It may be hypothesised that as the bioavailable background concentration of an
      essential metal increases (within natural limits), the natural tolerance (to the
      metal) of the acclimated/adapted organisms and communities will increase. In this
      study the influence of acclimation to different copper concentrations on the
      sensitivity of the freshwater cladoceran Daphnia magna Straus was investigated.
      D. magna was acclimated over three generations to environmentally relevant copper
      concentrations ranging from 0.5 to 100 microg Cu/l (copper activity: 7.18 x 10(
      15) to 3700 x 10(-12) M Cu2+). A modified standard test medium was used as
      culture and test medium. Medium modifications were: reduced hardness (lowered to
      180 mg CaCO3/l) and addition of Aldrich humic acid at a concentration of 5 mg
      DOC/l (instead of EDTA). The effects of acclimation on these organisms were
      monitored using acute mortality assays and long-term assays in which life table
      parameters, copper body concentrations and energy reserves were used as test
      endpoints. Our results showed a two-fold increase in acute copper tolerance with
      increasing acclimation concentration for second and third generation organisms.
      Copper acclimation concentrations up to 35 microg Cu/l (80 pM Cu2+) did not
      affect the net reproduction and the intrinsic growth rate. The energy reserves of
      the acclimated daphnids revealed an Optimal Concentration range (OCEE) and
      concentrations between 5 and 12 microg Cu/l (0.5-4.1 pM Cu2+) and 1 and 35 microg
      Cu/l (0.023-80 pM Cu2+) seemed to be optimal for first and third generation
      daphnids, respectively. Lower and higher copper concentrations resulted in
      deficiency and toxicity responses. It was also demonstrated that up to 35 microg
      Cu/l, third generation daphnids were able to regulate their total copper body
      concentration. These results clearly indicate that bioavailable background copper
      concentrations present in culture media have to be considered in the evaluation
      of toxicity test results, especially when the toxicity data are used for water
      quality guideline derivation and/or ecological risk assessment for metals.

PMID- 14659460
TI  - Effects of cadmium on the reproductive axis of Japanese medaka (Oryzias latipes).
AB  - Cadmium (Cd) is a ubquitous element and a significant inorganic pollutant that
      has previously been found to bioaccumulate in reproductive organs of fish and
      disrupt important endocrine processes, especially those involved in synthesis,
      release and metabolism of hormones. Clearly, there is potential for reproductive
      effects in fish populations exposed to Cd, however, few studies have investigated
      the non-lethal consequences of Cd in fish. To this extent, adult male and female
      Japanese medaka were exposed to 0-10 ppb Cd for 7 weeks. Reproductive endpoints
      were monitored during weeks 6 and 7 of exposure and compared to physiological
      responses along the hypothalamus-pituitary-gonadal (HPG) axis, including plasma
      vitellogenin (VTG), hepatic estrogen receptor (ER), plasma steroids, gonadal
      somatic indices (GSI), and gonadal steroid release. There were no observed
      effects on VTG and ER by long-term Cd exposure. However, gonadal steroid release
      was significantly decreased in males and females at all exposure concentrations
      and female plasma estradiol levels were significantly altered at concentrations
      higher than 5 ppb Cd. Overall, responses along the HPG axis were more sensitive
      to Cd exposure than the reproductive and developmental endpoints, which were not
      affected in this study, indicating that higher level impairment in fish might be
      relatively protected.

PMID- 14659461
TI  - Bile acid composition in snake bile juice and toxicity of snake bile acids to
      rats.
AB  - We determined the bile acid profiles in bile juice of snake gallbladders by HPLC
      on a silica gel RP-18 reversed-phase column. Cholic acid and chenodeoxycholic
      acid were predominant components in three of four snake species. To elucidate the
      toxic effect of snake bile acids on rats, a synthetic bile acid mixture was
      prepared mimicking the bile acid composition of a snake Naja naja atra bile
      juice. Twenty-four male Wistar rats were divided into four groups and treated
      orally at 3-day intervals with saline (control group) and different doses (1-3x
      doses) of the bile acid mixture. After treatment, the following parameters
      increased: the relative ratios of liver and kidney mass to body mass, the
      concentrations of red blood cell, hemoglobin and hematocrit in the blood,
      aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,
      plasma urea nitrogen and creatinine in the plasma, and the levels of urine urea
      nitrogen and creatinine in the urine. Body mass of rats and the levels of Na+,
      K+, Ca++ in the urine of rats were significantly decreased, especially for groups
      treated with 2x and 3x doses of the bile acid mixture. Examination of liver and
      kidney pathology also showed cell enlargement and lesion in cell integrity in
      treated groups, especially for groups treated with 2x and 3x bile acid mixture,
      indicating that short-term toxicity of snake N. naja atra bile acids was
      significant in rats.

PMID- 14659462
TI  - The molecular basis of retinoid action in tumors.

PMID- 14659463
TI  - Transcription factor cascades in congenital heart malformation.

PMID- 14659464
TI  - Cancer immunotherapy: simply cell biology?

PMID- 14659465
TI  - IL-15 in the life and death of lymphocytes: immunotherapeutic implications.

PMID- 14659466
TI  - Uncoupling protein 2: a novel player in neuroprotection.

PMID- 14659467
TI  - T-cell priming in bone marrow: the potential for long-lasting protective anti
      tumor immunity.

PMID- 14659468
TI  - Gene microarray analysis of multiple sclerosis lesions.

PMID- 14659469
TI  - Serotonin receptors: guardians of stable breathing.
AB  - Disturbances of breathing arising from failures of the respiratory center are not
      uncommon. Among them, breath holding and apnea occur most frequently as
      consequences of pulmonary and cardiac diseases, hypoxia, head trauma, cerebral
      inflammatory processes, genetic defects, degenerative brain diseases, alcoholism,
      deep anesthesia and drug overdose. They are often life-threatening and fail to
      respond to existing pharmacotherapies. After extensive research, there is now a
      reliable basis for new strategies to treat respiratory disturbances by
      pharmacological manipulation of intracellular signaling pathways, particularly
      those involving the serotonin receptor family. Specific activation of these
      pathways effectively prevails respiratory disturbances and can be extended to
      treatment of life-threatening respiratory disorders in patients.

PMID- 14659470
TI  - Inflammation meets oxidation: NF-kappaB as a mediator of initial lesion
      development in atherosclerosis.
AB  - Transcription factor nuclear factor-kappaB (NF-kappaB) and its target genes are
      involved in the pathogenesis of atherosclerosis, in addition to many other
      diseases. Monocyte recruitment into subendothelial space is primarily mediated by
      NF-kappaB-dependent gene expression, and this event is a crucial milestone,
      because it is nearly impossible to reverse the progression of the lesion after
      this point. Recent advances in our understanding of atherosclerosis as a disease
      of childhood enforces the necessity of developing novel approaches for prevention
      and treatment. Here, the authors address NF-kappaB as a major therapeutic target,
      especially for preventive measures, in the light of two main hypotheses of
      atherosclerosis: oxidation and inflammation.

PMID- 14659471
TI  - Molecular aspects of bile formation and cholestasis.
AB  - Recent insights into the cellular and molecular mechanisms that control the
      function and regulation of hepatobiliary transport have led to a greater
      understanding of the physiological significance of bile secretion. Individual
      carriers for bile acids and other organic anions in both liver and intestine have
      now been cloned from several species. In addition, complex networks of signals
      that regulate key enzymes and membrane transporters located in cells that
      participate in the metabolism or transport of biliary constituents are being
      unraveled. This knowledge has major implications for the pathogenesis of
      cholestatic liver diseases. Here, we review recent information on molecular
      aspects of hepatobiliary secretory function and its regulation in cholestasis.
      Potential implications of this knowledge for the design of new therapies of
      cholestatic disorders are also discussed.

PMID- 14659472
TI  - Stress effects on limbic function and behavior.

PMID- 14659473
TI  - Conditioning and residual emotionality effects of predator stimuli: some
      reflections on stress and emotion.
AB  - The advantages of using predator-related odor stimuli to study emotional
      responses in laboratory tests depend on whether such stimuli do elicit a
      relatively complete pattern of emotionality. This has been confirmed for cat
      fur/skin odor stimuli, which elicit a range of defensive behaviors in rats that
      may be reduced by anxiolytic drugs, produce residual anxiety-like behavior in the
      elevated plus maze and support rapid aversive conditioning to the context in
      which they were encountered. Although the synthetic fox fecal odor,
      trimethylthiazoline (TMT), elicits avoidance similar to that seen in response to
      cat fur/skin odor, this avoidance does not respond to anxiolytic drugs. In
      addition, TMT does not produce residual anxiety-like behaviors in the elevated
      plus maze, nor does it support conditioning. As natural cat feces also elicit
      avoidance but fail to support conditioning, it is possible that the ability of a
      predator-related odor to serve as an effective unconditioned stimulus (US)
      relates to its predictive status with reference to the actual presence of the
      predator. Avoidance per se may reflect that a stimulus is aversive but not
      necessarily capable of eliciting an emotional response. This view is consonant
      with findings in a Mouse Defense Test Battery (MDTB) measuring a wide range of
      defensive responses to predator exposure. A contextual defense measure that may
      reflect either conditioned or residual but unconditioned emotional responses was
      almost never reduced by drug effects unless these also reduced risk assessment or
      defensive threat/attack measures. However, reductions in contextual defense
      without changes in flight/avoidance measures were much more common. These
      findings suggest that flight/avoidance, although it obviously may occur as one
      component of a full pattern of defensive and emotional behaviors, is also
      somewhat separable from the others. When-as appears to be the case with TMT-it is
      the major or perhaps only consistent defensive behavior elicited, this may
      reflect a stimulus that is aversive or noxious but with little ability to predict
      the presence of threat or danger. That such stimuli fail to support rapid
      aversive conditioning suggests the need for a reanalysis of the characteristics
      required for an effective aversive US.

PMID- 14659474
TI  - The effect of social factors on the anxiolytic efficacy of buspirone in male
      rats, male mice, and men.
AB  - Earlier findings suggest that housing conditions in laboratory animals and life
      events in humans influence the efficacy of anxiolytic drugs. Here we report on
      the impact of social isolation on buspirone efficacy in male mice and rats as
      assessed by the elevated plus-maze. In addition, the impact of social support on
      buspirone efficacy was assessed in male patients. When administered 30 min before
      testing and irrespective of housing conditions, buspirone significantly
      suppressed locomotor activity both in mice (6 mg/kg) and rats (10 mg/kg) and, as
      such, other behavioral changes observed at this time point must be seen as
      behaviorally nonselective. However, these locomotor disruptive effects of
      buspirone were not evident in either species at longer injection-test intervals
      (2 and 4 h). When given 2 h prior to testing, a low (3 mg/kg) but not high (10
      mg/kg) dose of buspirone increased the frequency of open arm exploration in rats
      (but not mice) irrespective of housing conditions. At the longest injection-test
      interval used (4 h), buspirone increased the duration of open arm exploration in
      individually housed, but not group-housed, rats. Similar, though somewhat less
      robust, effects were observed in male mice at this time. In a double-blind
      placebo-controlled study with male patients, chronic buspirone treatment (3 x 10
      mg daily for 6 weeks) produced a highly significant reduction in scores on the
      Hamilton Rating Scale for Anxiety (HAM-A). Multiple regression analysis of social
      support received by patients indicated that the support of nonrelatives (but not
      of family or other relatives) was a strong positive predictor of buspirone
      efficacy. Taken together, our data support the hypothesis that social conditions
      affect the anxiolytic efficacy of buspirone. Results are discussed in relation to
      differences in the social organization of the three species investigated.

PMID- 14659475
TI  - Differential involvement of amygdaloid CRH system(s) in the salience and valence
      of the stimuli.
AB  - Anxiety is a heterogeneous term encompassing not only state or trait
      characteristics but also a wide range of pathologies such as generalized anxiety
      disorders, phobias, panic and obsessive-compulsive disorders, acute stress
      disorder, and posttraumatic stress disorder. Given that diverse forms of anxiety
      exist, numerous animal models have been developed, which are considered to be
      useful in identifying mechanisms underlying anxiety states. Examples of such
      animal models include paradigms that assess the behavioral response to neurogenic
      (or painful stimuli) or psychogenic stressors or to cues that had previously been
      associated with painful stimuli. The present report presents data regarding the
      impact of stressors on corticotropin-releasing hormone (CRH), and relates these
      to changes in anxiety-like states. Specifically, we demonstrate that (1)
      psychogenic stressors influence the in vivo release of CRH at the central nucleus
      of the amygdala (CeA); (2) although CRH changes within the CeA are exquisitely
      sensitive to stressors, they are also elicited by positive stimuli; and (3) while
      treatment with diazepam attenuates behavioral signs of anxiety, the CRH release
      associated with a stressor is unaffected by the treatment. The position is
      offered that although release of CRH within the CeA is increased under stressful
      conditions, it is not a necessary condition for the consequent behavioral
      expression of anxiety-like reactions, at least not in minimally threatening
      situations. We suggest that the CRH responses at the CeA may be involved in a
      preparatory capacity and, as such, may accompany a range of emotionally
      significant stimuli, be they appetitive or aversive.

PMID- 14659476
TI  - Systems mediating acute glucocorticoid effects on memory consolidation and
      retrieval.
AB  - It is well established that glucocorticoid hormones, secreted by the adrenal
      cortex after a stressful event, influence cognitive performance. This article
      reviews recent findings from this laboratory on the acute effects of
      glucocorticoids in rats on specific memory phases, i.e., memory consolidation and
      memory retrieval. Posttraining activation of glucocorticoid-sensitive pathways
      involving glucocorticoid receptors (GRs) enhances memory consolidation in a dose
      dependent manner. Glucocorticoid influences on memory consolidation depend on
      noradrenergic activation of the basolateral complex of the amygdala (BLA) and
      interactions of the BLA with other brain regions. By contrast, memory retrieval
      processes are usually impaired with high circulating levels of glucocorticoids or
      following infusions of GR agonists into the hippocampus. Although the BLA does
      not appear to be a site of glucocorticoid action in influencing memory retrieval,
      an intact BLA is required for enabling glucocorticoid effects on memory
      retrieval. The BLA appears to be a key structure in a memory-modulatory system
      that regulates, in concert with other brain regions, stress and glucocorticoid
      effects on both memory consolidation and memory retrieval.

PMID- 14659477
TI  - Amygdala kindling increases fear responses and decreases glucocorticoid receptor
      mRNA expression in hippocampal regions.
AB  - Amygdala kindling dramatically increases fearful behavior in rats. Because
      kindling-induced fear increases in magnitude as rats receive more stimulations,
      kindling provides an excellent model for studying the nature and neural
      mechanisms of fear sensitization. In the present experiment, we studied whether
      the development of kindling-induced fear is related to changes in glucocorticoid
      receptor (GR) mRNA expression in various brain regions. Rats received 20, 60 or
      100 amygdala kindling stimulations or 100 sham stimulations. One day after the
      final stimulation, their fearful behavior was assessed in an unfamiliar open
      field. Then, the rats were sacrificed and their brains were processed for in situ
      hybridization of GR mRNA expression. We found that compared with the sham
      stimulated rats, the rats that received 60 or 100 kindling stimulations were
      significantly more fearful in the open field and also had significantly less GR
      mRNA expression in the dentate gyrus and CA1 subfield of the hippocampus.
      Importantly, the changes in fearful behavior were significantly correlated with
      the changes in GR mRNA expression. These results suggest that alterations in GR
      mRNA expression in hippocampal regions may play a role in the development of
      kindling-induced fear.

PMID- 14659478
TI  - Sex- and hemisphere-related influences on the neurobiology of emotionally
      influenced memory.
AB  - Recent findings are beginning to reveal apparently pronounced influences of both
      sex and cerebral hemisphere on the neurobiology of emotionally influenced memory.
      In this article, I first provide a brief, general overview of sex-related
      influences on brain and cognition. I next describe recent findings from my
      laboratory and others demonstrating sex-related influences on neural mechanisms
      underlying emotionally influenced explicit recall of emotionally arousing events.
      Both the hemispheric involvement of the human amygdala in memory for emotionally
      arousing events and the impairing effect of beta-adrenergic blockade on memory
      for emotional events, exhibit sex-related differences. I hypothesize that both of
      these effects relate to a modulatory influence of each amygdala on ipsilateral
      hemispheric function. Specifically, I hypothesize that the right hemisphere
      amygdala modulates right hemispheric processing of global/central aspects of a
      situation (an effect more pronounced in males), while the left hemisphere
      amygdala modulates left hemispheric processing of more local/fine detail aspects
      of a situation (an effect more pronounced in females). More generally, these
      findings presented here suggest that the interacting influences of sex and
      cerebral hemisphere on emotionally influenced memory are more pronounced than has
      been widely appreciated to date.

PMID- 14659479
TI  - Phosphorylated cyclic AMP response element binding protein expression induced in
      the periaqueductal gray by predator stress: its relationship to the stress
      experience, behavior and limbic neural plasticity.
AB  - Electrophysiological studies in cats and recently in rats implicate
      neuroplasticity in the periaqueductal gray (PAG) and its afferents in stressor
      induced increases in fearful behavior and anxiety-like behavior (ALB). Such
      increases may model aspects of affective changes following traumatic stress in
      humans. The present study explored the role of neuroplasticity in PAG and its
      connection with the central nucleus of the amygdala (ACE) in male rodent anxiety
      like response to predator stress. In the first of two studies, the effects of
      predator stress on the induction of phosphorylated cyclic AMP response element
      binding protein (pCREB) were investigated. pCREB expression in the PAG and
      ventromedial hypothalamus (VMH) was examined immunohistochemically. Predator
      stress increased the degree of pCREB expression in PAG cells (measured
      densitometrically) but did not increase the number of cells expressing pCREB
      (measured stereologically). Moreover, predator stress-specific increase in pCREB
      like immunoreactivity (lir) was restricted to the right lateral column of the
      PAG. In addition, pCREB lir in the right lateral column likely reflects aspects
      of the stress experience because the stressor (cat behavior) and the response to
      the stressor (rat defensive behavior) are highly predictive of degree of pCREB
      expression. There was no effect of predator stress on pCREB lir in the VMH.
      Because pCREB expression has been associated with long-lasting potentiation (LLP)
      of neural transmission, we examined the effects of predator stress on
      transmission in the ACE-PAG pathway in a second study. Predator stress elevated
      evoked potential measures of ACE-PAG transmission in the right hemisphere but not
      in the left hemisphere 11-12 days after predator stress. This finding is
      consistent with the longer-lived effects of pharmacological stress on amygdalo
      PAG transmission in the right hemisphere but not in the left hemisphere in cats.
      Of interest is the fact that the same aspects of the stressor experience and
      reaction to it, which are predictive of the degree of pCREB expression, are also
      highly predictive of the degree of potentiation of measures of ACE-PAG
      transmission. Behavioral analyses revealed that the most consistent effects of
      predator stress are on behavior in the plus maze (open arm exploration and risk
      assessment) and on startle. In addition, covariance analysis suggests that ACE
      PAG potentiation mediates some but not all of the changes in ALB produced by
      predator stress. Because pCREB expression may be a precursor to neuroplastic
      changes in certain forms of memory and LLP, the present findings complement
      studies in the cat, showing that neuroplastic changes in the PAG underlie changes
      in affect following stress. Furthermore, these findings suggest that neuroplastic
      changes in PAG may be important mediators of predator stress-induced changes in
      affective behavior in rodents. Finally, consistent with cat and human studies,
      the right hemisphere appears particularly important in long-term response to
      stress.

PMID- 14659481
TI  - Lipid drug delivery and rational formulation design for lipophilic drugs with low
      oral bioavailability, applied to cyclosporine.
AB  - By using a rational formulation approach, we have tried to find the general
      characteristics for promising self-emulsifying drug delivery systems (SEDDS)
      based on natural lipid components, for the oral delivery of lipophilic drugs.
      Galactolipids, which are polar lipids commonly found in the chloroplast membranes
      of green plants, and a natural part of the human diet, were the main surfactants
      in these formulations. This was done in three clinical studies: a screening
      study, followed by a prediction study and, finally, a confirmatory study; in all
      17 experimental formulations were investigated. The clinical trials were
      performed in healthy volunteers. Cyclosporine, a well-known lipophilic peptide,
      was incorporated in different SEDDS, and administered orally, followed by the
      measurement of the blood concentration of the drug over time. The pharmacokinetic
      parameters, which describe the rate and extent of absorption, were estimated. We
      found that fractionated oat oil (FOO) and medium chain monoglycerides (60:30:10
      mono-, di- and tri-glycerides) promoted absorption, and resulted in a formulation
      with absorption characteristics nearly equal to the commercial formulation of
      cyclosporine, Sandimmun Neoral.

PMID- 14659482
TI  - Cytotoxicity and DNA binding properties of the plant alkaloid burasaine.
AB  - Burasaine is a plant alkaloid isolated from the roots of several species of the
      Burasaia genus endemic to Madagascar. It exhibits in vitro antiplasmodial
      activities but the molecular basis of this biological activity is not known. The
      strong structural similarity with the alkaloid berberine prompted us to postulate
      that burasaine could interact with DNA. To test this hypothesis, we investigated
      the mode of binding of burasaine to DNA and tested its cytotoxic potential toward
      human HL-60 leukemia cells. Its inhibitory activity toward topoisomerases I and
      II was also studied. Absorption and melting temperature measurements attested
      that burasaine forms stable complexes with DNA. The results of electric linear
      dichroism (ELD) spectroscopy may be interpreted either by an intercalation or by
      an external stacking parallel to the base pairs. The affinity of burasaine for
      DNA is slightly lower than that of berberine and this translates at the cellular
      level by a reduced cytotoxicity. Burasaine does not promote DNA cleavage by human
      topoisomerases I or II and this likely accounts for its very weak cytotoxic
      potential and its very modest effects on the cell cycle progression observed at
      high concentrations. The study identifies DNA as a potential bioreceptor for
      burasaine and contributes to a better understanding of the mechanism of action of
      benzoquinolizine alkaloids.

PMID- 14659483
TI  - PAMPA--a drug absorption in vitro model. 5. Unstirred water layer in iso-pH
      mapping assays and pKa(flux)--optimized design (pOD-PAMPA).
AB  - Iso-pH mapping unstirred parallel artificial membrane permeability assay (PAMPA)
      was used to measure the effective permeability, P(e), as a function of pH from 3
      to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic
      acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases
      (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic
      weak base (quinine). The intrinsic permeability, P(o), the unstirred water layer
      (UWL) permeability, P(u), and the apparent pK(a) (pK(a)(flux)) were determined
      from the pH dependence of logP(e). The underlying permeability-pH equations were
      derived for multiprotic weak acids, weak bases and ampholytes. The average
      thickness of the unstirred water layer on each side of the membrane was estimated
      to be nearly 2000 microm, somewhat larger than that found in Caco-2 permeability
      assays (unstirred). Since the UWL thickness in the human intestine is believed to
      be about forty times smaller, it is critical to correct the in vitro permeability
      data for the effect of the UWL. Without such correction, the in vitro
      permeability coefficient of lipophilic molecules would be indicative only of the
      property of water. In single-pH PAMPA (e.g. pH 7.4), the uncertainty of the UWL
      contribution can be minimized if a specially-selected pH (possibly different from
      7.4) were used in the assay. From the analysis of the shapes of the log P(e)-pH
      plots, a method to improve the selection of the assay pH, called pK(a)(flux)
      optimized design (pOD-PAMPA), was described and tested. From an optimally
      selected assay pH, it is possible to estimate P(o), as well as the entire
      membrane permeability-pH profile.

PMID- 14659484
TI  - Sustained release of water-soluble drug from directly compressed alginate
      tablets.
AB  - The release of acetyl salicylic acid from directly compressed alginate tablets
      was investigated. The effect of the amount and type of alginate on the drug
      release rate was evaluated in different formulations. Four different grades of
      alginate were used. The in vitro release studies were carried out using the
      apparatus II (paddle) equipment as described in the USP 23/NF dissolution
      monograph. Dissolution medium was 0.1 M HCl for 2 h followed by phosphate buffer
      pH 6.8; both at 37 degrees C. Sustained drug release up to 16 h was achieved
      using sodium alginate in combination with dibasic calcium phosphate.

PMID- 14659485
TI  - Experimental and modelistic approach to explain granulate inhomogeneity through
      preferential growth.
AB  - Wet granulation of a powder mixture often leads to accumulation of the smallest
      particles in the large granules. The preferential uptake of these particles
      results in an inhomogeneous granulate. The aim of this study was to investigate
      the mechanism of preferential growth. For that purpose the growth of one single
      granule was followed by adding a droplet of binder liquid to a rotating powder
      mixture of paracetamol and lactose. The particle sizes of both components were
      varied. At various time points mass and paracetamol content of the granule was
      determined. The results showed in all cases that the fine particles have a
      relatively higher presence in the granule than the coarse particles. These
      observations were independent of the fact whether the fine particles consists of
      lactose or paracetamol. During layering growth of the granule, caused by radial
      penetration of the liquid, fine particles appear to have a higher affinity for
      growth than coarse particles. It was argued that small particles penetrate the
      pores of the granule more easily than large particles, leading to the
      preferential absorption of the fine constituents. A model based on this growth
      mechanism, was able to predict the experimental results. It was concluded that
      this non-random growth process underlies the formation of inhomogeneous granules.

PMID- 14659486
TI  - Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes.
AB  - The objective of this study was to assess the in vivo fate of poly(2
      (dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous
      administration into mice. Circulation kinetics and tissue distribution in terms
      of plasmid localization and transfection efficiency were assessed. To gain more
      insight into the observed biodistribution and gene expression profile, the
      interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and
      albumin) was investigated in vitro. In the case of i.v. injection of positively
      charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found
      in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA
      polyplexes with a negative charge, uptake occurred mainly by the liver.
      Administration of positively charged complexes at a 30 microg DNA dose resulted
      in reporter gene expression primarily in the lungs. Injection of negatively
      charged complexes and naked plasmid did not result in luciferase expression in
      any of the organs examined. In vitro turbidity experiments showed the induction
      of a charge dependent aggregation process upon addition of albumin to the
      polyplexes pointing out to the involvement of aggregate formation in the dominant
      lung uptake of the positively charged polyplexes. Also, incubations of polyplexes
      after pre-incubation with a physiological concentration of albumin with washed
      erythrocytes confirmed that polyplexes induce the formation of extremely large
      structures. This paper underlines the need for the design of systems with reduced
      interaction with blood components to promote the delivery of DNA to target
      tissues outside the lungs.

PMID- 14659487
TI  - Interactions of ibuprofen with cationic polysaccharides in aqueous dispersions
      and hydrogels. Rheological and diffusional implications.
AB  - Non-steroidal antiinflammatory drugs, such as ibuprofen, are amphiphilic
      substances capable of self-association in aqueous solutions and able to be sorbed
      onto polymers through hydrophobic and electrostatic bonds. The aim of this work
      was to analyze the association processes of sodium ibuprofen with cationic
      celluloses (Celquat H-100 (PQ-4) and SC-230 M (PQ-10)) and cationic guar gums
      (Ecopol 261-S and 14-S) and their repercussions on the properties of the aqueous
      dispersions and cross-linked hydrogels. The interaction process was studied in
      aqueous dispersions through transmittance, surface tension, fluorescence,
      conductivity, viscosity and oscillatory rheometry measurements. Below cmc, the
      drug molecules weakly interact with the polymers through hydrophobic and ionic
      interactions. Around the cmc (4%), a notable decrease in the viscosity, and
      storage and loss moduli of the dispersions (even precipitation in PQ-10 systems)
      was observed. An additional increase in drug concentration induced the
      dispersions to recover their initial properties. Since ibuprofen/polymer cationic
      groups ratio were in all cases above 1, these observations indicate that drug
      self-association induces the polymer to coil around the micelles and, as the
      number of micelles increases (more drug concentration) the polymer chains
      interact with more of them, uncoiling again to some extent. Polymer (1%)
      dispersions containing 6% ibuprofen showed drug diffusion coefficients much lower
      than in water. When a surfactant, sodium dodecylsulfate, was added to these
      systems the diffusion coefficients decreased even more, suggesting the formation
      of new associative structures. Chemically cross-linked hydrogels made of these
      cationic polysaccharides absorb considerable amounts of ibuprofen (up to 15 g/g)
      and showed a pH-dependent release process. At acidic pH, drug-polymer affinity is
      maintained, preventing drug release. In contrast, at pH 8 the interactions are
      broken and the release process is sustained for more than 4h. In summary,
      ibuprofen interactions with cationic polysaccharides strongly determine the
      performance of their aqueous dispersions and hydrogels.

PMID- 14659488
TI  - Effect of omeprazole on the anticoagulant activity and the pharmacokinetics of
      warfarin enantiomers in rats.
AB  - The effect of the proton pump inhibitor omeprazole on the anticoagulation and the
      pharmacokinetics of warfarin enantiomers was studied in rats. Omeprazole given
      intraperitoneally in a daily dose of 0.67 mg/kg over 8 days had no significant
      effect on the absorption, distribution and the total serum clearance values of
      the S- and R-enantiomers of warfarin. Omeprazole did not affect the pre-treatment
      baseline blood coagulation and the in vitro rat serum protein binding of warfarin
      enantiomers. In vitro study with rat liver microsomes showed that omeprazole had
      an inhibitory effect on the hydroxylation of warfarin enantiomers. Results
      obtained from in vivo urinary excretion study revealed that omeprazole inhibited
      the formation clearance of both S- and R-form oxidative metabolites, but
      increased that of the overall reductive metabolites, and the renal clearance of S
      and R-enantiomers, of warfarin. As a consequence, the total serum clearance
      values for warfarin enantiomers remained unchanged and the hypoprothrombinaemic
      response produced by warfarin was not affected.

PMID- 14659489
TI  - CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic
      patients.
AB  - Clozapine is an effective atypical antipsychotic drug applied in the treatment of
      resistant schizophrenia. The drug is mainly metabolized by cytochrome P-450 (CYP)
      enzymes especially the isozyme CYP1A2. Remarkably, the effective dosage varies
      widely among patients, making it necessary to individualize drug therapy with
      clozapine. The explanation for dosage variation may be differences in drug
      metabolism, and more specifically of CYP1A2 activity. This study is aimed at
      determining to what extent variability in clozapine dose can be explained by
      pharmacokinetic (PK) factors and more specifically by CYP1A2 activity in
      effectively treated psychiatric patients. In 22 evaluable patients with a
      schizophrenic disorder chronically using clozapine, the CYP1A2 activity and the
      clozapine clearance were estimated. For calculation of the pharmacokinetic
      parameters of clozapine, population PK software based upon Bayesian analysis was
      used. Caffeine clearance was estimated with the paraxanthine/caffeine ratio and
      served as estimate of CYP1A2 activity.A significant linear relationship was found
      between the clozapine dose and clozapine clearance (R: 0.71; P<0.05), whereas no
      relationship was found between clozapine dosage and clozapine serum trough
      concentration. Moreover, individual caffeine and clozapine clearances were found
      to be significantly related (R: 0.62; P<0.05) as were clozapine dose per kg body
      weight and P/C mol ratio (R: 0.44; P<0.05). We conclude that CYP1A2 activity is
      an important determinant of the variability of effective clozapine doses in
      psychiatric patients.

PMID- 14659490
TI  - Delivery of liposomes in dry powder form: aerodynamic dispersion properties.
AB  - OBJECTIVE: In our previous study, we reported a novel approach of delivering
      liposomes in dry powder form that relies on spontaneous formation of liposomes
      upon dispersion of micronised phospholipid(s) based powders in an aqueous
      environment, thereby creating reservoirs for the encapsulation of drugs [J.
      Pharm. Sci. 91 (2002) 482]. In this paper, we demonstrate the in vitro generation
      of aerosols from these novel powders. METHODOLOGY: Various formulations
      comprising different phospholipid(s) exhibiting different physico-chemical
      properties were prepared. Aerosol was generated using a deagglomeration rig
      wherein the powder was entrained at a flow rate of 60 l/min and high turbulence
      was generated using air-jets. Two antimicrobial agents (ciprofloxacin and CM3, a
      novel peptide) and a bronchodilator, salbutamol sulfate, were used as model drugs
      to examine the powder dispersion properties. RESULTS: The deagglomeration rig
      used in this study was able to disperse 87-95% of the total loaded powder into
      the cascade impactor. Amongst the various formulations comprising different
      phospholipid(s), DMPG and (DMPC+DMPG) based formulations exhibited excellent
      aerodynamic dispersion properties. Fine particle fractions (FPF) of more than 50%
      were achieved for these formulations for three model drugs. Encapsulation of the
      model drugs in the FPF, obtained upon dispersion of these novel powders, is also
      discussed in this paper. An encapsulation of approximately 35, 40 and 25% was
      achieved in the FPF for ciprofloxacin, CM3 peptide and salbutamol sulfate,
      respectively.

PMID- 14659491
TI  - Drug release from reservoir pellets compacted with some excipients of different
      physical properties.
AB  - The aim of the present study was to investigate the influence of the size and the
      porosity of excipient microcrystalline cellulose (MCC) particles on the
      densification and the deformation during compaction and the consequent effect on
      the drug release from reservoir pellets. Drug pellets consisting of salicylic
      acid and microcrystalline cellulose were prepared by extrusion-spheronisation and
      spray-coated with ethyl cellulose (ethanol solution). Excipient pellets of
      different size and porosity were prepared by extrusion-spheronisation or direct
      spheronisation. Five binary mixtures of reservoir pellets and excipient particles
      were prepared in the proportion 1:7 and lubricated. After compaction the
      reservoir pellets were retrieved and analysed to determine the intragranular
      porosity, surface area, shape and drug release. The reservoir pellets were shown
      to undergo extensive deformation and densification during compaction, resulting
      in a preserved or even prolonged drug release time. The mode of deformation of
      the reservoir pellets seems to be critical for the compression-induced change in
      drug release. Formation of large indents has a negative effect on the release
      time, while the use of small particles or small deformable agglomerates has a
      protective effect. We also hypothesize that the coating structure changes during
      compaction and the final structure of the coating is the net effect of two
      parallel processes, one reducing and one prolonging the drug transport time
      across the coating.

PMID- 14659492
TI  - Left planum temporale: an anatomical marker of left hemispheric specialization
      for language comprehension.
AB  - We report on a study aimed at investigating the relationships between handedness,
      anatomical data and functional data related to speech processing. Twenty subjects
      with variable handedness (Edinburgh score ranging from -100 to 100) underwent
      both anatomical magnetic resonance imaging (MRI) and Positron Emission Tomography
      (PET) during story listening and rest. The surface areas of the left and right
      planum temporale (PT) were measured on each subject's MRI scan. A multiple
      regression analysis of PET data was conducted using these PT surface areas as
      well as handedness scores as predictors. The surface of the left PT explained a
      significant part of the functional variability. We observed that subjects who had
      the larger left PT were likely to show a larger leftward functional asymmetry of
      several perisylvian areas, namely the inferior parietal lobule outside the supra
      marginal gyrus (the angular gyrus and the cortex above), Heschl's gyrus, the
      rolandic operculum, and the temporal pole. The size of the right PT explained
      only a little part of functional variability and we found no evidence that the
      anatomical asymmetry of the PT explained functional variability. In addition, we
      could not evidence any relationship between handedness and functional data. These
      results, which confirm previous work, argue for a perceptive origin of
      hemispheric specialization for language comprehension as has been suggested by
      others.

PMID- 14659493
TI  - A direct measure of human lateral temporal lobe neurons responsive to face
      matching.
AB  - Do the human cerebral hemispheres process faces differently? Clinical lesion
      observations and primate studies suggest that the right temporal lobe is critical
      in face processing. Yet, the nature of this relationship remains unclear.
      Recording from single neurons during a visuospatial (VS)-matching paradigm, we
      found that 100% of significantly active neurons discriminated matching from
      perception, bilaterally. Lateralized differences in the nature and timing of
      responses revealed that the right hemisphere neurons responded earlier, and with
      uniform frequency reductions. Additional lateralized differences favoring the
      right hemisphere neurons were found when subjects matched intact faces compared
      to scrambled faces or complex objects. We conclude that widely distributed neural
      ensembles are involved in 'lateralized' behaviors, but cerebral specialization of
      face processing is as much a function of the nature and timing of neuronal
      activity as anatomic location.

PMID- 14659494
TI  - Dissociable brain mechanisms for inhibitory control: effects of interference
      content and working memory capacity.
AB  - In this study, event-related fMRI was used to examine whether the resolution of
      interference arising from two different information contents activates the same
      or different neuronal circuitries. In addition, we examined the extent to which
      these inhibitory control mechanisms are modulated by individual differences in
      working memory capacity. Two groups of participants with high and low working
      memory capacity [high span (HS) and low span (LS) participants, respectively]
      performed two versions of an item recognition task with familiar letters and
      abstract objects as stimulus materials. Interference costs were examined by means
      of the recent negative probe technique with otherwise identical testing
      conditions across both tasks. While the behavioral interference costs were of
      similar magnitude in both tasks, the underlying brain activation pattern differed
      between tasks: The object task interference-effects (higher activation in
      interference trials than in control trials) were restricted to the anterior
      intraparietal sulcus (IPS). Interference effects for familiar letters were
      obtained in the anterior IPS, the left postero-ventral and the right dorsolateral
      prefrontal cortex (PFC) as well as the precuneus. As the letters were more
      discernible than the objects, the results suggest that the critical feature for
      PFC and precuneus involvement in interference resolution is the saliency of
      stimulus-response mappings. The interference effects in the letter task were
      modulated by working memory capacity: LS participants showed enhanced activation
      for interference trials only, whereas for HS participants, who showed better
      performance and also lower interference costs in the letter task, the above
      mentioned neuronal circuitry was activated for interference and control trials,
      thereby attenuating the interference effects. The latter results support the view
      that HS individuals allocate more attentional resources for the maintenance of
      task goals in the face of interfering information from preceding trials with
      familiar stimulus materials.

PMID- 14659495
TI  - The N1 hypothesis and irrelevant sound: evidence from token set size effects.
AB  - This study investigated how increases in the number of different types of sound
      (token set size) within a heard but ignored sequence influence brain activity and
      performance in a serial recall task (the irrelevant sound effect). We tested the
      hypothesis that brain processes affected by the refractory state of the neuronal
      populations involved in generating the auditory N1 play a role in the memory
      disruption produced by irrelevant sound. Auditory event-related potentials (ERPs)
      were recorded when volunteers performed a serial recall task that required
      remembering lists of visually presented numbers that were followed by a
      distractor-filled retention interval. The results showed that both increments in
      set size from 1 to 2 and from 2 to 5 elicited an increase of the N1 amplitude.
      Furthermore, increases in set size from 2 to 5, but not from 1 to 2, caused a
      significant decrease of the serial recall performance. This result suggested
      that, if N1 were to play a role in the disruption produced by irrelevant sound,
      the processes underlying the N1 wave may only serve as a necessary rather than a
      sufficient condition for disruption.

PMID- 14659496
TI  - Combined analysis of DTI and fMRI data reveals a joint maturation of white and
      grey matter in a fronto-parietal network.
AB  - The aim of this study was to explore whether there are networks of regions where
      maturation of white matter and changes in brain activity show similar
      developmental trends during childhood. In a previous study, we showed that during
      childhood, grey matter activity increases in frontal and parietal regions. We
      hypothesized that this would be mediated by maturation of white matter. Twenty
      three healthy children aged 8-18 years were investigated. Brain activity was
      measured using the blood oxygen level-dependent (BOLD) contrast with functional
      magnetic resonance imaging (fMRI) during performance of a working memory (WM)
      task. White matter microstructure was investigated using diffusion tensor imaging
      (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an
      indicator of myelination and axon thickness. Prior to scanning, WM score was
      evaluated. WM score correlated independently with FA values and BOLD response in
      several regions. FA values and BOLD response were extracted for each subject from
      the peak voxels of these regions. The FA values were used as covariates in an
      additional BOLD analysis to find brain regions where FA values and BOLD response
      correlated. Conversely, the BOLD response values were used as covariates in an
      additional FA analysis. In several cortical and sub-cortical regions, there were
      positive correlations between maturation of white matter and increased brain
      activity. Specifically, and consistent with our hypothesis, we found that FA
      values in fronto-parietal white matter correlated with BOLD response in closely
      located grey matter in the superior frontal sulcus and inferior parietal lobe,
      areas that could form a functional network underlying working memory function.

PMID- 14659497
TI  - Cross-form conceptual relations between sounds and words: effects on the novelty
      P3.
AB  - In order for cross-form conceptual priming to occur, the brain must extract an
      amodal representation of the presented concept. To determine whether the novelty
      P3 would show such cross-form effects, novel, environmental sounds or their
      verbal equivalents were repeated two blocks after their first presentation in two
      cross-form conditions, word-sound (e.g., the word "pig" followed by the sound
      "oink") or sound-word. Conceptual repetition engendered an asymmetric reduction
      in novelty P3 amplitude, i.e., amplitude was reduced in the sound-word but not in
      the word-sound condition. The data suggest that the novelty P3 reflects an
      evaluative stage of processing in which some semantic information is extracted.
      However, the lack of amplitude reduction for the word-sound condition implies
      that, at least at the delays used here, repetition as a conceptually equivalent
      sound may have failed to make contact with the initial verbal concept.

PMID- 14659498
TI  - Electrophysiological indicators of phonetic and non-phonetic multisensory
      interactions during audiovisual speech perception.
AB  - We studied the interactions in neural processing of auditory and visual speech by
      recording event-related brain potentials (ERPs). Unisensory (auditory - A and
      visual - V) and audiovisual (AV) vowels were presented to 11 subjects. AV vowels
      were phonetically either congruent (e.g., acoustic /a/ and visual /a/) or
      incongruent (e.g., acoustic /a/ and visual /y/). ERPs to AV stimuli and the sum
      of the ERPs to A and V stimuli (A+V) were compared. Similar ERPs to AV and A+V
      were hypothesized to indicate independent processing of A and V stimuli.
      Differences on the other hand would suggest AV interactions. Three deflections,
      the first peaking at about 85 ms after the A stimulus onset, were significantly
      larger in the ERPs to A+V than in the ERPs to both congruent and incongruent AV
      stimuli. We suggest that these differences reflect AV interactions in the
      processing of general, non-phonetic, features shared by the acoustic and visual
      stimulus (spatial location, coincidence in time). The first difference in the
      ERPs to incongruent and congruent AV vowels peaked at 155 ms from the A stimuli
      onset. This and two later differences are suggested to reflect interactions at
      phonetic level. The early general AV interactions probably reflect modified
      activity in the sensory-specific cortices, whereas the later phonetic AV
      interactions are likely generated in the heteromodal cortices. Thus, our results
      suggest that sensory-specific and heteromodal brain regions participate in AV
      speech integration at separate latencies and are sensitive to different features
      of A and V speech stimuli.

PMID- 14659499
TI  - Learning complex arithmetic--an fMRI study.
AB  - Aim of the present functional magnet resonance imaging (fMRI) study was to detect
      modifications of cerebral activation patterns related to learning arithmetic.
      Thirteen right-handed subjects were extensively trained on a set of 18 complex
      multiplication problems. In the following fMRI session, trained and untrained
      problems (closely matched for difficulty) were presented in blocked order
      alternating with a number matching task and a fact retrieval task. Importantly,
      left hemispheric activations were dominant in the two contrasts between untrained
      and trained condition, suggesting that learning processes in arithmetic are
      predominantly supported by the left hemisphere. Contrasting untrained versus
      trained condition, the left intraparietal sulcus showed significant activations,
      as well as the inferior parietal lobule. A further significant activation was
      found in the left inferior frontal gyrus. This activation may be accounted for by
      higher working memory demands in the untrained as compared to the trained
      condition. Contrasting trained versus untrained condition a significant focus of
      activation was found in the left angular gyrus. Following the triple-code model
      [Science 284 (1999) 970], the shift of activation within the parietal lobe from
      the intraparietal sulcus to the left angular gyrus suggests a modification from
      quantity-based processing to more automatic retrieval. The present study shows
      that the left angular gyrus is not only involved in arithmetic tasks requiring
      simple fact retrieval, but may show significant activations as a result of
      relatively short training of complex calculation.

PMID- 14659500
TI  - Semantic decision making in early probable AD: a PET activation study.
AB  - We studied the neural correlates of semantic decision making in early probable
      Alzheimer disease patients and age-matched controls by measuring changes in
      relative cerebral blood flow by PET (oxygen-15) while they performed a category
      specific word-matching task with either animal or artefact names. In comparison
      to a baseline (matching words by physical identity), semantic decision making
      elicited increased blood flow in the left frontal lobe (BA 6, 11, 47) and in the
      contralateral cerebellum in the controls. The only category-specific difference
      in controls was activation of the left supplementary motor area (BA 6) when
      making decisions on artefacts. In contrast, the patients recruited more extensive
      brain regions, encompassing areas in the left frontal lobe (BA 44, 45, 47), right
      occipital cortex (BA 18), midbrain, and the cerebellum bilaterally. Behaviorally,
      the patients performed the tasks with equal success albeit more slowly. No animal
      artefact differences emerged in the patients' activation patterns, indicating
      that their activation increases reflected a generalized, presumably compensatory
      reaction to higher task demands in the face of a progressive neurological
      disease.

PMID- 14659501
TI  - Successful episodic memory retrieval of newly learned faces activates a left
      fronto-parietal network.
AB  - It is easier to recognize a familiar face than a newly learned face. The neural
      basis of familiar face recognition has been elucidated in functional imaging and
      lesion studies. Behavioural and neuropsychological data indicate, however, that
      brain systems involved in episodic retrieval of familiar and newly learned faces
      are distinct. In our study, 12 subjects viewed 30 novel faces in an encoding
      session. In the study condition, event-related functional magnetic resonance
      imaging (fMRI) was used to compare brain activation during correct recognition of
      the recently learned faces to that observed during correct rejection of unknown
      control faces. Differences were present in the left inferior parietal (BA 40) and
      left medial frontal/anterior cingulate (BA 32/9) cortex. These two regions may be
      part of a pathway in the dorsal visual stream, responsible for a "feeling of
      familiarity" in contrast to the ventral pathway in the temporal lobes, which is
      mainly involved in the recognition of personal identity.

PMID- 14659502
TI  - Covert and overt voluntary attention: linked or independent?
AB  - Recent evidence indicates that reflexive shifts in spatial attention with eye
      movements (overt orienting) and without eye movements (covert orienting) can be
      dissociated [J. Exp. Psychol. Hum. Percept. Perform., in press]. Here, we show
      that a similar dissociation exists for voluntary shifts in overt and covert
      attention. Our study is consistent with general theories of attention that assume
      bottom-up (reflexive) processes and top-down (voluntary) processes converge on a
      common neural architecture.

PMID- 14659503
TI  - Numbers need to care.

PMID- 14659504
TI  - Neurons involved in the exteroceptive function of pain.

PMID- 14659505
TI  - Epidemiology of chronic non-malignant pain in Denmark.
AB  - A series of health surveys are conducted every sixth to seventh year in Denmark.
      In the most recent survey of 2000, a national random sample (>16 years) was drawn
      from the Danish Central Personal Register. Out of the original sample 12,333
      (74%) were interviewed and of these 10,066 returned a completed questionnaire (SF
      36). The present study includes only those who both took part in the interview
      and the postal questionnaire. Cancer patients were excluded. Persons suffering
      from chronic pain (PG) were identified through the question 'Do you have
      chronic/long lasting pain lasting 6 months or more'? An overall chronic pain
      prevalence of 19% was found -16% for men and 21% for women. Prevalence of chronic
      pain increased with increasing age. Persons >/=67 years had 3.9 higher odds of
      suffering from chronic pain than persons in the age group 16-24 years. Compared
      with married persons, divorced or separated persons had 1.5 higher odds of
      chronic pain. Odds for chronic pain were 1.9 higher among those with an education
      of less than 10 years compared with individuals with an education of 13 years or
      more. During a 14-day period reporters of chronic pain had an average of 0.8 days
      (range 0-10) lost due to illness compared with an average of 0.4 days (range 0
      10) for the control group (CG) (Odds Ratio (OR)) 2.0). Persons with a job which
      required high physical strain were more likely to report chronic pain compared
      with those with a sedentary job (OR 2.2). The odds of quitting one's job because
      of ill health were seven times higher among people belonging to the PG. A strong
      association between chronic pain and poor self-rated health was also
      demonstrated. The PG had twice as many contacts with various health professionals
      compared with the CG, and the health care system was, on average, utilised 25%
      more (overall contacts) by the PG than by the general population. Among the
      persons in the PG, 33% were not satisfied with the examinations carried out in
      connection with their pain condition and 40% were not satisfied with the
      treatment offered. Nearly 130,000 adults, corresponding to 3% of the Danish
      population, use opioids on a regular basis. Opioids are used by 12% of the PG.

PMID- 14659506
TI  - Chronic hyperalgesia induced by repeated acid injections in muscle is abolished
      by the loss of ASIC3, but not ASIC1.
AB  - Clinically, chronic pain and hyperalgesia induced by muscle injury are disabling
      and difficult to treat. Cellular and molecular mechanisms underlying chronic
      muscle-induced hyperalgesia are not well understood. For this reason, we
      developed an animal model where repeated injections of acidic saline into one
      gastrocnemius muscle produce bilateral, long-lasting mechanical hypersensitivity
      of the paw (i.e. hyperalgesia) without associated tissue damage. Since acid
      sensing ion channels (ASICs) are found on primary afferent fibers and respond to
      decreases in pH, we tested the hypothesis that ASICs on primary afferent fibers
      innervating muscle are critical to development of hyperalgesia and central
      sensitization in response to repeated intramuscular acid. Dorsal root ganglion
      neurons innervating muscle express ASIC3 and respond to acidic pH with fast,
      transient inward and sustained currents that resemble those of ASICs. Mechanical
      hyperalgesia produced by repeated intramuscular acid injections is prevented by
      prior treatment of the muscle with the non-selective ASIC antagonist, amiloride,
      suggesting ASICs might be involved. ASIC3 knockouts do not develop mechanical
      hyperalgesia to repeated intramuscular acid injection when compared to wildtype
      littermates. In contrast, ASIC1 knockouts develop hyperalgesia similar to their
      wildtype littermates. Extracellular recordings of spinal wide dynamic range (WDR)
      neurons from wildtype mice show an expansion of the receptive field to include
      the contralateral paw, an increased response to von Frey filaments applied to the
      paw both ipsilaterally and contralaterally, and increased response to noxious
      pinch contralaterally after the second intramuscular acid injection. These
      changes in WDR neurons do not occur in ASIC3 knockouts. Thus, activation of
      ASIC3s on muscle afferents is required for development of mechanical hyperalgesia
      and central sensitization that normally occurs in response to repeated
      intramuscular acid. Therefore, interfering with ASIC3 might be of benefit in
      treatment or prevention of chronic hyperalgesia.

PMID- 14659507
TI  - Interferon-gamma induces characteristics of central sensitization in spinal
      dorsal horn neurons in vitro.
AB  - Hyperexcitability of spinal dorsal horn neurons, also known as 'central
      sensitization', is a component of pain associated with pathological conditions in
      the nervous system. The aim of the present study was to analyze if the pro
      inflammatory cytokine, interferon-gamma (IFN-gamma), which can be released for
      extended periods of time in the nervous system during inflammatory and infectious
      events, can alter synaptic activity in dorsal horn neurons and thereby contribute
      to such hyperexcitability. Treatment of cultured dorsal horn neurons with IFN
      gamma for 2 weeks resulted in a significantly reduced clustering of alpha-amino-3
      hydroxy-5-methylisoxazole (AMPA) receptor subunit 1 (GluR1) that was dependent on
      nitric oxide. The neurons displayed an increased frequency and amplitude of
      excitatory postsynaptic currents (EPSCs) upon IFN-gamma treatment. Treated dorsal
      horn neurons also exhibited increased responsiveness to stimulation of dorsal
      root ganglia (DRG) axons in a two-compartment model. Furthermore, disinhibition
      by the GABA(A) receptor antagonist picrotoxin (PTX) significantly increased EPSC
      frequency and induced bursting in untreated cultures but did not significantly
      increase the frequency in treated neurons, which displayed bursting even without
      PTX. GABA(A) agonists reduced activity more strongly in treated cultures and
      immunochemical staining for GABA(A) receptors showed no difference from controls.
      Since GluR1-containing AMPA receptors (AMPARs) occur predominantly on inhibitory
      neurons in the dorsal horn, we suggest that the IFN-gamma-mediated increase in
      spontaneous activity and responsiveness to DRG axon stimulation, decrease in
      sensitivity to PTX and tendency for EPSC bursting result from a reduced
      expression of GluR1 on these neurons and not from a reduction in active GABA(A)
      receptors in the network. IFN-gamma thereby likely causes disinhibition of
      synaptic activity and primary afferent input in the dorsal horn, which
      consequently results in central sensitization.

PMID- 14659508
TI  - Changes in temporomandibular pain and other symptoms across the menstrual cycle.
AB  - The objective of this study was to assess changes in levels of clinical
      temporomandibular (TMD) pain in relation to phases of the menstrual cycle. TMD
      cases were 35 women not using oral contraceptives (OCs); 35 women using OCs; and
      21 men. Controls were 35 normally cycling women without TMD or other chronic
      pains. Subjects kept daily diaries over three menstrual cycles, reporting average
      and worst pain, general and premenstrual symptoms. Data were subject-centered and
      de-trended using the residuals from a random-effects linear regression model. To
      test for cyclic variation, cycles were standardized to 28 days and data were
      grouped into 9 periods/cycle (Days 1-3, 4-6, em leader, 22-24, 25-28). Overall
      levels of average pain, worst pain and symptoms did not differ across TMD subject
      groups. For worst pain, multivariate analysis of variance revealed a
      statistically significant difference across 3-day periods for normally cycling
      women with TMD (P=0.011) and for women using OCs (P=0.017). In both groups, TMD
      pain levels rose toward the end of the cycle and peaked during menstruation. In
      women not using OCs, there was a secondary pain peak at Days 13-15, around the
      time of ovulation. This peak was not seen in women using OCs. There was no
      statistically significant difference over time periods for men (P=0.94). Similar
      patterns were found for average pain, as well as PMS symptoms and general somatic
      symptoms. These results suggest that TMD pain in women is highest at times of
      lowest estrogen, but rapid estrogen change may also be associated with increased
      pain.

PMID- 14659509
TI  - Can complex regional pain syndrome be painless?
AB  - While spontaneous and stimulus-evoked pain are the hallmarks of complex regional
      pain syndrome (CRPS), also known as reflex sympathetic dystrophy, autonomic
      abnormalities, motor dysfunction, and trophic changes in the affected limb are
      additional clinical characteristics distinguishing this syndrome. Even though the
      exact underlying mechanisms of the syndrome remain obscure, a recent hypothesis
      suggests that the abnormal response of neural nociceptive tissue plays a major
      role in the pathogenesis of CRPS via the mechanism known as 'neurogenic
      inflammation'. The group of patients presented here exhibited all the clinical
      characteristics of CRPS but had no pain, thereby indicating that ongoing or
      evoked pain is not a necessary condition for CRPS to be maintained. We suggest
      the term complex regional painless syndrome to describe this syndrome.

PMID- 14659510
TI  - The role of spinal nitric oxide and glutamate in nociceptive behaviour evoked by
      high-dose intrathecal morphine in rats.
AB  - Injection of high-dose of morphine into the spinal lumbar intrathecal (i.t.)
      space of rats elicits a nociceptive behavioural syndrome characterized by
      periodic bouts of spontaneous agitation and severe vocalization. The induced
      behavioural response such as vocalization and agitation was observed dose
      dependently by i.t. administration of morphine (125-500 nmol). Pretreatment with
      naloxone (s.c. and i.t.), an opioid receptor antagonist, failed to reverse the
      morphine-induced behavioural response. The excitatory effect of morphine was
      inhibited dose-dependently by pretreatment with 3-((+)2-carboxy-piperazin-4-yl)
      propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA)
      receptor antagonist and MK-801, a non-competitive NMDA receptor antagonist. The
      non-selective nitric oxide (NO) synthase inhibitor N(G)-nitro L-arginine methyl
      ester (L-NAME) inhibited dose-dependently the behavioural response to high-dose
      i.t. morphine (500 nmol), whereas D-NAME was without affecting the response to
      high-dose i.t. morphine. In the present study, we measured NO metabolites
      (nitrite/nitrate) in the extracellular fluid of rat dorsal spinal cord using in
      vivo microdialysis. The i.t. injection of morphine (500 nmol) evoked significant
      increases in NO metabolites and glutamate from the spinal cord. Not only NO
      metabolites but also glutamate released by high-dose morphine were reduced
      significantly by pretreatment with L-NAME (400 nmol). Pretreatment with CPP and
      MK-801 showed a significant reduction of the NO metabolites and glutamate levels
      elevated by high-dose i.t. morphine. These results suggest that the excitatory
      action of high-dose i.t. morphine may be mediated by an NMDA-NO cascade in the
      spinal cord.

PMID- 14659511
TI  - Blood pressure but not cortisol mediates stress effects on subsequent pain
      perception in healthy men and women.
AB  - Research has demonstrated that exposure to acute stress may attenuate pain
      perception. Mechanisms of this effect in humans have not been determined. This
      study was conducted to determine the extent to which psychophysiological and
      adrenocortical responses to acute stress predict subsequent pain perception. One
      hundred and fifty-two healthy participants (80 women) were assigned to one of two
      conditions: rest followed by the cold pressor test (CPT; N=76) or stress followed
      by CPT (N=76). The stress protocol consisted of a public-speaking challenge.
      Participants rated their pain every 15 s during a 90-s hand CPT (0-4 degrees C),
      and they completed the short form of the McGill Pain Questionnaire. Salivary
      cortisol, mood, blood pressure (BP), and impedance cardiography measures were
      collected in both conditions. Women had lower BP and reported greater pain than
      men in both conditions (ps<0.01). Participants in the stress condition reported
      less pain during CPT than those in the rest condition (p=0.02). Regression
      analyses demonstrated that the stress effect on pain ratings was mediated by
      systolic BP level during stress; however, cortisol responses did not affect this
      relationship. Mood changes were independent predictors of pain. The study
      demonstrates that BP changes in response to stress mediate the stress-induced
      attenuation of pain perception.

PMID- 14659512
TI  - Involvement of corticotropin-releasing hormone receptor subtypes 1 and 2 in
      peripheral opioid-mediated inhibition of inflammatory pain.
AB  - In painful inflammation, exogenous as well as endogenous corticotropin-releasing
      hormone (CRH) can release opioid peptides (mainly beta-endorphin) from various
      types of immune cells and produce antinociception by activating opioid receptors
      on peripheral sensory nerve endings. CRH mediates its central effects through two
      high-affinity membrane receptors, the CRH receptor subtypes 1 and 2. It is
      unclear at present whether the peripheral antinociceptive effects of CRH are
      mediated through CRH receptor 1 (CRH R1) or CRH receptor 2 (CRH R2). Employing a
      double-immunocytochemical technique, this study investigated in Wistar rats with
      Freund's complete adjuvant-induced hind paw inflammation whether immune cells
      within blood and inflamed subcutaneous tissue express CRH R1 and/or CRH R2
      together with the opioid peptide beta-endorphin (END). Additionally, we examined
      using selective CRH R1 and CRH R2 antagonists whether peripheral CRH-induced
      antinociception is mediated by the respective CRH receptor subtypes. We found a
      high degree of co-expression of END together with both CRH R1 and CRH R2 in
      macrophage/monocytes, granulocytes and lymphocytes within blood and inflamed
      subcutaneous tissue. Also we observed a high degree of co-localization of CRH R1
      and CRH R2 receptors on circulating and resident immune cells. Both the selective
      CRH R1 antagonist CP-154,526 and the selective CRH R2 antagonist astressin 2B
      significantly attenuated peripheral antinociceptive effects of CRH indicating the
      involvement of both CRH receptor subtypes. Taken together, these findings suggest
      that in inflammatory pain CRH-induced peripheral antinociception is mediated via
      both CRH R1 and CRH R2 located on END containing immune cells within inflamed
      sites.

PMID- 14659513
TI  - Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine
      gluconate for breakthrough pain in cancer patients.
AB  - Patients with controlled background pain associated with cancer frequently also
      experience episodes of moderate to severe intensity breakthrough pain. Opioid
      pharmacotherapy, particularly with oral morphine, remains the cornerstone for the
      management of cancer pain. Nasal administration of opioids provides a mechanism
      for more rapid drug absorption and more rapid onset of pain relief compared with
      oral dosing. This non-randomized, open-label, uncontrolled investigation
      evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of
      nasal morphine gluconate, administered to cancer patients in response to an
      episode of breakthrough pain. Single dose nasal morphine gluconate administered
      to 11 patients was associated with effective plasma morphine concentrations (mean
      C(max) 64 ng/ml; range 33.8-121 ng/ml) and low plasma morphine metabolites
      (morphine-6-glucuronide mean C(max) 114 ng/ml; range 46-189 ng/ml; morphine-3
      glucuronide mean C(max) 572 ng/ml; range 257-990 ng/ml). Side effects were minor
      and limited to nasal irritation. Patients reported rapid onset of pain relief
      (perceptible pain relief achieved in 10/11 patients, time to onset 2.4+/-2.1 min;
      and meaningful pain relief, achieved in five patients, 6.8+/-7.3 min to onset,
      mean t(max) 0.36 h). Pain intensity scores were significantly reduced at all
      times after dosing; pain relief scores were unchanged. Patient satisfaction
      ratings were high. These results show that nasal morphine has rapid absorption
      and apparent onset of effect. Additional multi-dose, dose-ranging and placebo
      controlled studies of nasal morphine for cancer pain are warranted.

PMID- 14659514
TI  - The association between anger expression and chronic pain intensity: evidence for
      partial mediation by endogenous opioid dysfunction.
AB  - Recent work suggests that an expressive anger management style (anger-out) is
      associated with elevated acute pain sensitivity due to endogenous opioid
      antinociceptive dysfunction. We tested the hypothesis that this opioid
      dysfunction mediates the previously reported positive association between anger
      out and chronic pain intensity. To assess endogenous opioid antinociception in
      the laboratory, 71 subjects with chronic low back pain received opioid blockade
      (8 mg naloxone i.v.) or placebo in counterbalanced order in separate sessions.
      During each, subjects participated in a 1-min finger pressure pain task followed
      by an ischemic forearm pain task, providing acute pain ratings on the McGill Pain
      Questionnaire-Short Form (MPQ) immediately following each task. Subjects also
      completed a 7-day chronic pain diary based on the MPQ between laboratory
      sessions. To index opioid antinociceptive function, blockade effects were
      derived, subtracting placebo from blockade condition pain ratings. Greater anger
      out was associated with both smaller blockade effects (suggesting impaired opioid
      antinociception) and greater chronic pain intensity, and blockade effects were
      inversely associated with chronic pain intensity. Sequential hierarchical
      regressions suggested that opioid dysfunction partially mediates the positive
      association between anger-out and total MPQ chronic pain intensity. Inclusion of
      blockade effects in the first step of the regression resulted in a decrease from
      7 to 3% in chronic pain variance accounted for by anger-out. Opioid dysfunction
      did not mediate the positive association between anger-in and chronic pain. These
      results provide preliminary support for the hypothesis that the positive
      association between anger expression and chronic pain intensity is mediated by
      opioid antinociceptive system dysfunction.

PMID- 14659515
TI  - Genotype-dependence of gabapentin and pregabalin sensitivity: the pharmacogenetic
      mediation of analgesia is specific to the type of pain being inhibited.
AB  - The antiepileptic drug, gabapentin, and another structurally related compound,
      pregabalin, are increasingly employed in the pharmacotherapy of chronic pain
      states, although their primary mechanism of action remains a topic of active
      study. A genomic approach to the study of these drugs may elucidate their
      potentially novel mechanisms. We examined the heritability of sensitivity to
      analgesia from gabapentin and pregabalin as a precursor to linkage mapping
      efforts. Accordingly, 11 inbred mouse strains were tested for inhibition of
      nociception by gabapentin or pregabalin (50-300 mg/kg, i.p.) in two different
      preclinical assays of inflammatory pain, the formalin test (5% formalin; 20
      microl) and zymosan thermal hyperalgesia on the paw-withdrawal test (3 mg/ml
      zymosan; 20 microl). Significant strain-dependence of drug action was noted in
      each case, indicating that sensitivity to these analgesics is heritable.
      Furthermore, the pattern of strain sensitivities to gabapentin and pregabalin
      were mostly similar, supporting the notion that they act via similar genetic and
      physiological mechanisms. However, there was virtually no correlation between
      strain sensitivities to pregabalin inhibition of formalin nociception and zymosan
      thermal hyperalgesia. In light of previous data from our laboratory and others
      regarding morphine analgesia, we now establish and empirically demonstrate the
      general principle that pharmacogenetic mechanisms underlying analgesic
      sensitivity are specific to the type of pain being inhibited. This has
      considerable implications for ongoing pharmacogenetic investigations and, more
      generally, for the choices of preclinical models of pain used in drug
      development.

PMID- 14659516
TI  - Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.
AB  - OBJECTIVE: To provide recommendations for the core outcome domains that should be
      considered by investigators conducting clinical trials of the efficacy and
      effectiveness of treatments for chronic pain. Development of a core set of
      outcome domains would facilitate comparison and pooling of data, encourage more
      complete reporting of outcomes, simplify the preparation and review of research
      proposals and manuscripts, and allow clinicians to make informed decisions
      regarding the risks and benefits of treatment. METHODS: Under the auspices of the
      Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials
      (IMMPACT), 27 specialists from academia, governmental agencies, and the
      pharmaceutical industry participated in a consensus meeting and identified core
      outcome domains that should be considered in clinical trials of treatments for
      chronic pain. CONCLUSIONS: There was a consensus that chronic pain clinical
      trials should assess outcomes representing six core domains: (1) pain, (2)
      physical functioning, (3) emotional functioning, (4) participant ratings of
      improvement and satisfaction with treatment, (5) symptoms and adverse events, (6)
      participant disposition (e.g. adherence to the treatment regimen and reasons for
      premature withdrawal from the trial). Although consideration should be given to
      the assessment of each of these domains, there may be exceptions to the general
      recommendation to include all of these domains in chronic pain trials. When this
      occurs, the rationale for not including domains should be provided. It is not the
      intention of these recommendations that assessment of the core domains should be
      considered a requirement for approval of product applications by regulatory
      agencies or that a treatment must demonstrate statistically significant effects
      for all of the relevant core domains to establish evidence of its efficacy.

PMID- 14659517
TI  - Alterations in dorsal horn neurones in a rat model of cancer-induced bone pain.
AB  - Cancer-induced bone pain is a major clinical problem. A rat model based on intra
      tibial injection of MRMT-1 mammary tumour cells was used to mimic progressive
      cancer-induced bone pain. At the time of stable behavioural changes (decreased
      thresholds to mechanical and cold stimuli) and bone destruction, in vivo
      electrophysiology was used to characterize natural (mechanical, thermal, and
      cold) and electrical-evoked responses of superficial and deep dorsal horn
      neurones in halothane-anaesthetized rats. Receptive field size was significantly
      enlarged for superficial neurones in the MRMT-1 animals. Superficial cells were
      characterised as either nociceptive specific (NS) or wide dynamic range (WDR).
      The ratio of WDR to NS cells was substantially different between sham operated
      (growth media alone) (26:74%) and MRMT-1 injected rats (47:53%). NS cells showed
      no significant difference in their neuronal responses in MRMT-1-injected compared
      to sham rats. However, superficial WDR neurones in MRMT-1-injected rats had
      significantly increased responses to mechanical, thermal and electrical (A beta-,
      C fibre-, and post-discharge evoked response) stimuli. Deep WDR neurones showed
      less pronounced changes to the superficial dorsal horn, however, the response to
      thermal and electrical stimuli, but not mechanical, were significantly increased
      in the MRMT-1-injected rats. In conclusion, the spinal cord is significantly
      hyperexcitable with previously superficial NS cells becoming responsive to wide
      dynamic range stimuli possibly driving this plasticity via ascending and
      descending facilitatory pathways. The alterations in superficial dorsal horn
      neurones have not been reported in neuropathy or inflammation adding to the
      evidence for cancer-induced bone pain reflecting a unique pain state.

PMID- 14659518
TI  - Factor analysis validates the cluster structure of the dendrogram underlying the
      Multidimensional Affect and Pain Survey (MAPS) and challenges the a priori
      classification of the descriptors in the McGill Pain Questionnaire (MPQ).
AB  - The purpose of this study was to validate the content and structure of the
      Multidimensional Affect and Pain Survey (MAPS) by means of factor analysis. The
      101-MAPS is based on a dendrogram obtained by cluster analysis and contains 30
      clusters subsumed within three superclusters. If the MAPS is a valid
      questionnaire for the quantification of emotion and pain in patients, then factor
      analysis of patients' intensity ratings should produce factors which correspond
      to the cluster structure of the dendrogram. To confirm the structure of the
      dendrogram and hence, MAPS, factor analysis was applied to the responses by 100
      outpatients diagnosed with early stage cancer. Principal components analysis of
      responses to the MAPS yielded six factors. In accordance with the hypothesis, 13
      of the 17 clusters within the MAPS somatosensory pain supercluster loaded on
      three sensory factors: factor 1, severe sensory pain; factor 3, moderate sensory
      pain; and factor 6, numb/cold. Five of the eight clusters within the emotional
      pain supercluster loaded on factor 2, negative emotions. Four of the five
      clusters in the well-being supercluster loaded on factor 4, good health. Factor
      5, manageable illness was loaded on by clusters from the well-being supercluster
      and the somatosensory pain supercluster. The homogeneity of the six factors found
      demonstrate the validity of the MAPS and the cluster structure of the dendrogram.
      MAPS proved sensitive to sex differences; women endorsed the negative emotions
      factor more strongly than did men. The MAPS factors were much more homogeneous
      than those reported in the literature for the McGill Pain Questionnaire.

PMID- 14659519
TI  - Afferent fiber-selective shift in opiate potency following targeted opioid
      receptor knockdown.
AB  - Spinal application of opiates is the cornerstone of potent analgesia. In the
      present study, opiate analgesia was investigated after cutaneous application of a
      recombinant herpes simplex virus type-1 (HSV-1) encoding micro-opioid receptor
      (microOR) cDNA in reverse orientation with respect to the human cytomegalovirus
      early enhancer-promoter. Hind paw application of this recombinant vector was used
      in order to attenuate expression of the microOR in primary afferents and
      determine whether recombinant vector application would differentially affect the
      antinociceptive effects of the specific microOR agonist, [D-Ala(2),N-MePhe(4),Gly
      ol(5)] enkephalin (DAMGO), on behavioral responses mediated by C- and Adelta
      thermonociceptors. The recombinant vector encoding the Escherichia coli lacZ gene
      marker, KHZ, served as a control virus. Dorsal hind paw surfaces of female Swiss
      Webster mice were treated with one of these two viruses (1x10(8)pfu, 10 microl)
      or vehicle (uninfected). Immunohistochemistry and quantitative image analyses
      revealed decreased microOR expression in the superficial dorsal horns ipsilateral
      to hind paws treated with AMOR, but not KHZ. To add, behavioral foot withdrawal
      latencies of AMOR- and KHZ-treated hind paws demonstrated dose-dependent
      antinociception after intrathecal DAMGO administration. However, cutaneous
      application of dorsal hind paw surfaces treated with AMOR, but not KHZ, caused a
      rightward shift in the C-fiber dose-response, thus, indicating a loss of potency
      of intrathecal DAMGO. Loss or diminution of DAMGO potency during Adelta-fiber
      mediated responses was not observed. These immunohistochemistry and behavioral
      results of novel, recombinant HSV-1 vector microOR 'knock-down' in nociceptor
      afferent fibers provide additional evidence for presynaptic localization of
      microORs on central C-, but not Adelta-terminals.

PMID- 14659520
TI  - Induction of long-term potentiation of C fibre-evoked spinal field potentials
      requires recruitment of group I, but not group II/III metabotropic glutamate
      receptors.
AB  - In superficial layers of the lumbar spinal dorsal horn, N-methyl-D-aspartate
      dependent long-term potentiation (LTP) of C fibre-evoked field potentials, a
      synaptic model of central sensitisation and hyperalgesia, ensues the application
      of electrical high-frequency, high-intensity conditioning stimulation to the
      sciatic nerve. In order to investigate the putative involvement of the G protein
      coupled metabotropic glutamate receptors (mGluRs) in the induction of this form
      of LTP, we applied a series of mGluR antagonists exhibiting distinct group
      specific activity profiles to the spinal lumbar enlargement, prior to
      conditioning stimulation. The group I (mGluR1/5) and group II (mGluR2/3) mGluR
      antagonist (S)-alpha-methyl-4-carboxyphenylglycine or the selective mGluR1/5
      antagonist (S)-4-carboxyphenylglycine consistently impaired the development of
      spinal LTP. However, potentiation occurred in the presence of the inactive
      enantiomer (R)-alpha-methyl-4-carboxyphenylglycine. LTP proved insensitive to the
      selective mGluR2/3 antagonists (2S)-alpha-ethylglutamic acid and LY341495, either
      spinally or intravenously delivered. LTP could also be induced in the presence of
      the selective group III (mGluR4/mGluR6-mGluR8) mGluR antagonist (RS)-alpha
      methylserine-O-phosphate. However, none of the mGluR-active compounds alone
      noticeably altered the amplitudes of C fibre-evoked field potentials in the
      absence of conditioning stimulation. These findings suggest that the induction of
      LTP of C fibre-evoked field potentials in the spinal dorsal horn by high
      frequency, high-intensity stimulation of afferent C fibres requires a group
      specific mGluR recruitment, activation of mGluR1/5 but not that of mGluR4/6-8 and
      mGluR2/3 being a requisite step.

PMID- 14659521
TI  - Pharmacogenetic analysis of sex differences in opioid antinociception in rats.
AB  - Sex differences in opioid antinociception have been reported in rodents and
      monkeys, with opioids being more potent in males than females. In the present
      study, the influence of rat strain on sex differences in opioid antinociception
      was examined in a warm water tail-withdrawal procedure. Antinociceptive tests
      were conducted with the high-efficacy micro-opioid morphine, and the less
      efficacious opioids buprenorphine, butorphanol and nalbuphine. Baseline
      nociceptive latencies were consistently higher in males than their female
      counterparts. Sex differences in opioid antinociception were observed in all
      strains tested, with the opioids being more potent and/or effective in males. The
      magnitude of the sex differences was related to the relative efficacy of the
      opioid, with morphine, buprenorphine, butorphanol and nalbuphine being on average
      2.2-, 2.6-, 15.9- and 11.9-fold more potent in males. Sex differences also varied
      markedly across strains, with large differences consistently obtained in the F344
      and F344-Sasco strains, moderate differences in the ACI, DA, Lewis, Sprague
      Dawley, Wistar and Wistar-Kyoto strains, and small differences in the Long Evans
      Blue Spruce, Long Evans, Brown Norway and Holtzman strains. When compared across
      strains, there was no relationship between sex differences in nociceptive
      sensitivity and opioid sensitivity. These findings provide strong support for the
      role of genetic factors in determining sex differences in opioid antinociception,
      and suggest that the use of low-efficacy opioids, coupled with the use of rat
      strains that display small and large sex differences in opioid antinociception,
      may provide a sensitive tool to investigate the mechanisms underlying sex
      differences in opioid antinociception.

PMID- 14659522
TI  - Prospective examination of pain-related and psychological predictors of CRPS-like
      phenomena following total knee arthroplasty: a preliminary study.
AB  - We hypothesized that preoperative emotional distress and pain intensity would
      predict the occurrence of signs and symptoms of complex regional pain syndrome
      (CRPS) following total knee arthroplasty (TKA). Depression (Beck Depression
      Inventory, BDI), anxiety (State Trait Anxiety Inventory, STAI), pain (McGill Pain
      Questionnaire-Short Form, MPQ), and signs/symptoms meeting IASP criteria for CRPS
      were assessed preoperatively, and at 1-, 3-, and 6-months postoperatively in 77
      patients undergoing TKA. The prevalence of subjects fulfilling CRPS criteria was
      21.0% at 1 month, 13.0% at 3 months, and 12.7% at 6 months postoperative. Higher
      preoperative scores on the STAI predicted positive CRPS status at 1-month follow
      up (P<0.05), with a similar non-significant trend for preoperative BDI scores
      (P<0.10). Diagnostic sensitivity for the STAI was good (0.73), with moderate
      specificity (0.56). Neither measure predicted CRPS at later follow-up (P>0.10).
      Greater preoperative pain intensity predicted positive CRPS status at 3-month
      (MPQ-Sensory and MPQ-Affective; P<0.01) and 6-month (MPQ-Sensory) follow-up
      (P<0.01), but not at 1-month (P>0.10). Diagnostic sensitivity was high (0.83
      1.00), with moderate specificity (0.53-0.60). Post-TKA patients with CRPS were
      more depressed at 1-month follow-up (P<0.05) and more anxious at 6-month follow
      up (P<0.05) than patients with ongoing non-CRPS pain (all other comparisons non
      significant, P>0.10). Overall, results indicate that CRPS-like phenomena occur in
      a significant number of patients early post-TKA; however, it is not associated
      with significantly greater complaints of postoperative pain. There appears to be
      a modest utility for preoperative distress and pain in predicting CRPS signs and
      symptoms following TKA, although false positive rates are relatively high.

PMID- 14659523
TI  - The placebo needle, is it a valid and convincing placebo for use in acupuncture
      trials? A randomised, single-blind, cross-over pilot trial.
AB  - The issue of what constitutes an effective and realistic acupuncture placebo
      control has been a continuing problem for acupuncture research. In order to
      provide an effective placebo, the control procedure must be convincing, visible
      and should mimic, in all respects, apart from a physiological effect, the real
      active treatment. The 'Streitberger' needle might fulfil these criteria and this
      paper reports on a validation study. This was a single-blind, randomised, cross
      over pilot study. Patients were drawn from the orthopaedic hip and knee, joint
      replacement waiting list. Intervention consisted of either 2 weeks of treatment
      with real acupuncture followed by 2 weeks on placebo, or vice versa. The prime
      outcome was a needle sensation questionnaire and there was a range of secondary
      outcomes. Thirty-seven patients were randomised and completed treatment. Groups
      were well balanced at baseline. No significant differences between groups or
      needle types were found for any of the sensations measured. Most patients were
      unable to discriminate between the needles by penetration; however, nearly 40%
      were able to detect a difference in treatment type between needles. No major
      differences in outcome between real and placebo needling could be found. The fact
      that nearly 40% of subjects did not find that the two interventions were similar,
      however, raises some concerns with regard to the wholesale adoption of this
      instrument as a standard acupuncture placebo. Further work on inter-tester
      reliability and standardisation of technique is highly recommended before we can
      be confident about using this needle in further studies.

PMID- 14659524
TI  - Peripheral group II metabotropic glutamate receptors mediate endogenous anti
      allodynia in inflammation.
AB  - We previously demonstrated that activation of peripheral group II mGluRs inhibits
      PGE2-induced thermal hyperalgesia. In the present study we examined the role of
      peripheral group II mGluRs in inflammation-induced mechanical allodynia in CD1
      mice. Subcutaneous injection of group II mGluR agonists or antagonists into the
      plantar surface of the mouse hind paw did not alter mechanical thresholds,
      suggesting that peripheral group II mGluRs did not modulate basal mechanical
      sensation. We then used either PGE2 or carrageenan to induce mechanical allodynia
      and investigated the effects of activating or inhibiting peripheral group II
      mGluRs. PGE2-injected mice showed an 87+/-1% decrease of mechanical thresholds 75
      min after the injection, whereas mice injected with group II mGluR agonists had
      no increase in sensitivity compared to vehicle-injected mice. In the carrageenan
      induced inflammation model, 3 h after carrageenan injection the mechanical
      thresholds of mice injected with group II mGluR agonist APDC fully recovered to
      baseline levels while vehicle-injected mice showed only 43+/-8% recovery. The
      application of group II mGluR antagonist (LY341495) alone delayed the recovery of
      PGE2- and carrageenan-induced mechanical allodynia. Three hours after injection
      of carrageenan, LY341495-injected mice showed little or no recovery with
      mechanical thresholds 8+/-1% of pre-carrageenan baselines, compared to 57+/-8% of
      pre-carrageenan baselines in vehicle-injected mice at the same time point. Our
      results suggest that activation of peripheral group II mGluRs reduces
      inflammation-induced mechanical allodynia and that peripheral group II mGluRs may
      mediate endogenous anti-allodynia effects, which speed recovery from inflammation
      induced hypersensitivity.

PMID- 14659525
TI  - Pain tolerance as a predictor of outcome following multidisciplinary treatment
      for chronic pain: differential effects as a function of sex.
AB  - Sex-related differences in the experience of clinical and experimental pain have
      been widely reported. Females are at elevated risk for developing several chronic
      pain conditions and women demonstrate greater sensitivity to noxious stimulation
      in the laboratory. However, relationships between responses to experimental
      noxious stimuli and the experience of clinical pain have not been well
      characterized. One previous study of healthy adults indicated that pain threshold
      and tolerance were associated with clinical pain among women but not men (i.e.
      females with lower pain threshold and tolerance reported more clinical pain). In
      the present investigation, relationships between pain tolerance and outcomes of
      treatment for chronic pain were evaluated in a sex-dependent manner. Ischemic
      pain tolerance was assessed prior to treatment in 171 chronic pain patients
      completing a pain management program. Outcomes were measured as changes in pain
      severity, affect, and pain-related disability. Over the course of treatment,
      women demonstrated greater improvement in pain-related disability while men
      showed more reduction in pain. Ischemic pain tolerance was related to outcome in
      a sex-specific fashion. Women with higher pain tolerances showed greater
      improvement in pain, more reduction in pain-related interference, and more
      increases in activity level than women with lower pain tolerances. In contrast,
      pain tolerance was not associated with positive treatment outcomes among men.
      These results indicate that experimental pain responses may be most clinically
      relevant for women, and that sex differences may exist in the determinants of
      pain-treatment outcomes.

PMID- 14659526
TI  - Individual differences in diffuse noxious inhibitory controls (DNIC): association
      with clinical variables.
AB  - Laboratory pain research has been criticized as being irrelevant to the clinical
      experience of pain. Previous findings have been inconsistent with some studies
      suggesting that experimental pain responses may be related to the reported
      presence or severity of chronic pain, while others report no such associations.
      However, few of these studies assess a variety of laboratory pain responses, and
      none has assessed relationships between clinical pain and diffuse noxious
      inhibitory controls (DNIC) in healthy subjects. We administered questionnaire
      measures of pain, quality of life, and psychological variables to a sample of
      healthy adults participating in a laboratory study of age differences in pain
      responses. DNIC was not related to other laboratory pain responses, psychological
      variables, or physiological variables measured in the present study. Regression
      models predicting health-related quality of life (e.g. pain, physical
      functioning) revealed that age, sex, and DNIC responses explained between 10 and
      25% of the variance in these dependent measures. Of the laboratory pain
      variables, only DNIC was the sole consistent predictor of clinical pain and
      physical health, with greater DNIC responses related to less pain, better
      physical functioning, and better self-rated health. In addition, age differences
      in DNIC appeared to partially mediate age differences in physical functioning.
      These findings highlight the potential clinical relevance of experimental pain
      procedures and suggest that DNIC may be the laboratory pain response most closely
      associated with clinical pain and health-related variables.

PMID- 14659527
TI  - Agreement between percentage pain reductions calculated from numeric rating
      scores of pain intensity and those reported by patients with acute or cancer
      pain.
AB  - The use of percentage pain reduction is increasingly used to evaluate the
      effectiveness of pain treatments, but the degree of agreement between calculated
      percentage pain reduction (CPPR) as calculated from pre- and post-treatment
      levels of pain intensity and those reported directly by patients is unknown. Lack
      of agreement between these two measures could lead to errors in the determination
      of treatment effectiveness. We aimed to determine the agreement between CPPR and
      patient-reported percentage pain reduction (PRPPR). Patients with acute or cancer
      pain were asked to rate their pain intensity on a 0-10 verbal numerical rating
      scale (NRS) and to estimate the percent pain reduction from baseline pain after
      analgesic administration. They then received analgesics every 10 min until pain
      intensity declined to 4/10 or less. To evaluate agreement between CPPR and PRPPR,
      we computed the concordance correlation coefficient (CCC), which measures both
      accuracy and precision, and estimated the 95% limits of agreement for the
      differences between these two measures. 761 adult patients were enrolled. Female,
      healthy patients with acute pain of severe intensity and high levels of education
      predominated in the sample. The mean difference between CPPR and PRPPR was -2.6%
      (95% limits of agreement -12 to 17%). The CCC was 0.56 (accuracy was 0.9 and
      precision was 0.6). Although CPPR appeared to underestimate PRPPR in the higher
      range, this trend was not clinically important. The agreement between percentage
      pain reductions calculated from NRS scores and those estimated by patients did
      not vary according to gender or age. The good overall agreement between
      percentage pain reductions calculated from NRS scores and those estimated by
      patients suggests that these indices may be used interchangeably. The findings of
      this study extend existing patient-centered pain research and may be applied for
      the evaluation and comparison of pain treatments.

PMID- 14659528
TI  - The effects of protein phosphatase inhibitors on nociceptive behavioral responses
      of rats following intradermal injection of capsaicin.
AB  - The functions of crucial proteins in the nervous system are modulated by kinases
      and phosphatases which catalyze opposing reactions of phosphorylation and
      dephosphorylation. During spinal cord central sensitization, serine/threonine
      protein phosphatase 2A (PP2A) may play an important role in determining the
      excitability of nociceptive neurons in the spinal cord by modulating the
      phosphorylation state of some critical proteins. The effects of a general
      inhibitor of PP2A, okadaic acid (OA), and a specific inhibitor, fostriecin, on
      the behavioral responses of rats following capsaicin injection were investigated
      in this study. Hyperalgesia was initiated by injection of capsaicin into the
      plantar surface of the hindpaw of rats. An intrathecal catheter was previously
      implanted into the subarachnoid space of the spinal cord for the administration
      of a variety of drugs. Rats were tested for responses to mechanical stimuli using
      von Frey filaments of different bending forces applied at a site outside the area
      of injection. Responses to heat stimuli were detected from a site near the
      injection area. The responses were recorded before and after injection of
      capsaicin with the perfusion of ACSF, OA negative control, OA or fostriecin at
      different time points. The results demonstrated that secondary mechanical
      hyperalgesia and allodynia can be induced by the intradermal injection of
      capsaicin. Compared to administration of ACSF or the OA negative control,
      infusion of the phosphatase inhibitor OA or of fostriecin into the subarachnoid
      space enhanced the secondary mechanical hyperalgesia and allodynia by making the
      intradermal capsaicin-induced hyperalgesia and allodynia last longer.

PMID- 14659529
TI  - Pain coping strategies play a role in the persistence of pain in post-herpetic
      neuralgia.
AB  - Post-herpetic neuralgia (PHN) is a neuropathic pain state that is often difficult
      to treat. Although frequently discussed in the clinical literature, little is
      known about the impact of pain on daily function and the extent to which
      psychosocial factors, in particular pain coping strategies, influence adaptation
      to this chronic illness. In the context of a crossover pharmacological trial, 68
      patients with PHN completed a battery of psychological measures during a first
      drug-free baseline period. Following discontinuation of approximately 8 weeks of
      treatment, 49 of these patients completed data collection during a second drug
      free assessment prior to beginning a second drug phase. Twice-weekly telephone
      pain ratings were combined with questionnaire measures of perceived interference
      due to pain, overall activity level, depressive symptoms, and pain coping
      strategies. Cross-sectional hierarchical regression analyses indicated that
      catastrophizing correlated with depressive symptoms but not pain, and coping self
      statements were correlated with higher levels of overall activity. Prospective
      hierarchical regression analyses indicated that catastrophizing at baseline
      predicted level of pain 8 weeks later, an effect that was independent of baseline
      pain and depressive symptoms. Patients who reported increasing their activity in
      response to pain also reported more perceived interference due to pain 8 weeks
      later. Higher levels of ignoring pain sensations at baseline were prospectively
      correlated with more depressive symptoms 8 weeks later. These findings support a
      role for the continued investigation of cognitive-behavioral factors affecting
      the adaptation of elderly individuals experiencing PHN.

PMID- 14659530
TI  - NO-induced migraine attack: strong increase in plasma calcitonin gene-related
      peptide (CGRP) concentration and negative correlation with platelet serotonin
      release.
AB  - The aim of the present study was to investigate changes in the plasma calcitonin
      gene-related peptide (CGRP) concentration and platelet serotonin (5
      hydroxytriptamine, 5-HT) content during the immediate headache and the delayed
      genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs
      (without aura) and eight controls participated in the study. Sublingual
      nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital
      vein four times: 60 min before and after the nitroglycerin application, and 60
      and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12
      subjects). In those subjects who had no migraine attack (11 subjects) a similar
      time schedule was used. Plasma CGRP concentration increased significantly
      (P<0.01) during the migraine attack and returned to baseline after the cessation
      of the migraine. In addition, both change and peak, showed significant positive
      correlations with migraine headache intensity (P<0.001). However, plasma CGRP
      concentrations failed to change during immediate headache and in the subjects
      with no migraine attack. Basal CGRP concentration was significantly higher and
      platelet 5-HT content tended to be lower in subjects who experienced a migraine
      attack. Platelet serotonin content decreased significantly (P<0.01) after
      nitroglycerin in subjects with no migraine attack but no consistent change was
      observed in patients with migraine attack. In conclusion, the fact that plasma
      CGRP concentration correlates with the timing and severity of a migraine headache
      suggests a direct relationship between CGRP and migraine. In contrast, serotonin
      release from platelets does not provoke migraine, it may even counteract the
      headache and the concomitant CGRP release in this model.

PMID- 14659531
TI  - Spatial summation of pressure pain: effect of body region.
AB  - The characteristics of spatial summation of pressure pain are not clear. Pressure
      pain threshold (PPT) and perceived pressure pain intensity were measured in the
      hand, painfree back and myofascial trigger points (MTPs) in the back, using three
      different stimulus areas (0.5, 1 and 2 cm(2)). PPT decreased and perceived pain
      increased significantly with an increase in stimulation area in all the regions
      (e.g. PPT in the back, from 406+/-168 to 205+/-102kPa, P<0.0001). The magnitude
      of spatial summation of pressure pain was not significantly different between the
      regions. However, PPT in the back was significantly higher compared to the hand
      and MTPs (e.g. for 2 cm(2): mean of 205+/-102 vs 175+/-75 and 159+/-72kPa,
      P<0.01, respectively). Irrespective of body region, the quality of pain evoked
      with the large areas (1 and 2 cm(2)) was of pressure whereas in the small area
      (0.5 cm(2)) it was perceived as a prick. In conclusion, both PPT and perceived
      pressure pain intensity are subject to a considerable spatial summation in all
      the regions tested. The quality of pressure-evoked pain is probably determined by
      this spatial summation. Body region significantly affects the PPT level for a
      fixed stimulation area but not the magnitude of its spatial summation for areas
      up to 2 cm(2), which are probably within the receptive field of single spinal
      nociceptive neurons.

PMID- 14659532
TI  - The development of psychological changes following whiplash injury.
AB  - Psychological distress is a feature of chronic whiplash-associated disorders, but
      little is known of psychological changes from soon after injury to either
      recovery or symptom persistence. This study prospectively measured psychological
      distress (General Health Questionnaire 28, GHQ-28), fear of movement/re-injury
      (TAMPA Scale of Kinesphobia, TSK), acute post-traumatic stress (Impact of Events
      Scale, IES) and general health and well being (Short Form 36, SF-36) in 76
      whiplash subjects within 1 month of injury and then 2, 3 and 6 months post
      injury. Subjects were classified at 6 months post-injury using scores on the Neck
      Disability Index: recovered (<8), mild pain and disability (10-28) or
      moderate/severe pain and disability (>30). All whiplash groups demonstrated
      psychological distress (GHQ-28, SF-36) to some extent at 1 month post-injury.
      Scores of the recovered group and those with persistent mild symptoms returned to
      levels regarded as normal by 2 months post-injury, parallelling a decrease in
      reported pain and disability. Scores on both these tests remained above threshold
      levels in those with ongoing moderate/severe symptoms. The moderate/severe and
      mild groups showed elevated TSK scores at 1 month post-injury. TSK scores
      decreased by 2 months in the group with residual mild symptoms and by 6 months in
      those with persistent moderate/severe symptoms. Elevated IES scores, indicative
      of a moderate post-traumatic stress reaction, were unique to the group with
      moderate/severe symptoms. The results of this study demonstrated that all those
      experiencing whiplash injury display initial psychological distress that
      decreased in those whose symptoms subside. Whiplash participants who reported
      persistent moderate/severe symptoms at 6 months continue to be psychologically
      distressed and are also characterised by a moderate post-traumatic stress
      reaction.

PMID- 14659533
TI  - Transgenic mice possessing increased numbers of nociceptors do not exhibit
      increased behavioral sensitivity in models of inflammatory and neuropathic pain.
AB  - At least two classes of neciceptors can be distinguished based on their growth
      factor requirements: glial cell-line derived neurotrophic factor (GDNF)- and
      nerve growth factor (NGF)-dependent primary afferent neurons. Based on numerous
      anatomical and biochemical differences, GDNF- and NGF-dependent neurons have been
      proposed to be involved in the development of different types of persistent pain.
      To examine this hypothesis we used two lines of transgenic mice that contained a
      supernormal number of either NGF- or GDNF-dependent neurons (referred to as NGF
      OE and GDNF-OE mice, respectively). These mice were tested in a model of
      inflammatory pain (induced by injection of complete Freund's adjuvant) and
      neuropathic pain (using a spinal nerve ligation protocol). Contrary to
      expectations, neither line of transgenic mice became more hyperalgesic following
      induction of persistent pain. In fact, NGF-OE mice recovered more rapidly and
      became hypoalgesic despite extensive paw swelling in the inflammatory pain model.
      In the neuropathic pain model, only wildtype mice became hyperalgesic. Real-time
      PCR analysis showed that the NGF-OE and GDNF-OE mice exhibited changes in
      neuronal-specific mRNAs in the dorsal root ganglia but not the spinal cord dorsal
      horn. These results indicate that increasing the number of nociceptors results in
      potent compensatory mechanisms that may begin with changes in the sensory neurons
      themselves.

PMID- 14659534
TI  - Up-regulation of metabotropic glutamate receptor subtypes 3 and 5 in spinal cord
      in a clinical model of persistent inflammation and hyperalgesia.
AB  - Evidence from experimental pain research has revealed that metabotropic glutamate
      receptors (mGluRs) play a pivotal role in nociceptive processing, inflammatory
      pain and hyperalgesia. The aim of this study was to characterise expression of
      group I and II mGluRs in spinal cord in a model of naturally occurring persistent
      inflammation (sheep with unilateral lameness due to inflammation of the digital
      tissues of the feet, estimated to have been affected by the condition for >2
      weeks) and an experimental model of acute inflammation (injection of intradermal
      carrageenan into lower forelimb in sheep). Animals with unilateral clinical
      inflammation displayed significant mechanical hyperalgesia on the affected limb.
      Carrageenan treatment produced significant bilateral limb mechanical hyperalgesia
      3 h post-injection. Up-regulation of mGluR(3) and mGluR(5) mRNA was observed in
      ipsilateral spinal cord recovered from clinically lame animals, restricted to
      laminae II-V and I-II, respectively. Western blot analyses of protein extracts
      revealed a bilateral increase in mGluR(2/3) and mGluR(5). No change was detected
      in spinal cord mGluR(1) or mGluR(2) mRNA. There was no change in mGluR(1,2,3,5)
      subtype mRNA or proteins in spinal cord recovered from animals 3 h post
      carrageenan. These results demonstrate for the first time that mGluR subtypes are
      differentially expressed in spinal cord dorsal horn in response to persistent
      inflammation, and suggest that mGluR activity may be involved in mediating
      altered behaviours associated with clinical inflammatory pain.

PMID- 14659535
TI  - The cis-trans isomerase of unsaturated fatty acids in Pseudomonas and Vibrio:
      biochemistry, molecular biology and physiological function of a unique stress
      adaptive mechanism.
AB  - Isomerization of cis to trans unsaturated fatty acids is a mechanism enabling
      Gram-negative bacteria belonging to the genera Pseudomonas and Vibrio to adapt to
      several forms of environmental stress. The extent of the isomerization apparently
      correlates with the fluidity effects caused, i.e. by an increase in temperature
      or the accumulation of membrane-toxic organic compounds. Trans fatty acids are
      generated by direct isomerization of the respective cis configuration of the
      double bond without a shift of its position. The conversion of cis unsaturated
      fatty acids to trans is apparently instrumental in the adaptation of membrane
      fluidity to changing chemical or physical parameters of the cellular environment.
      Such an adaptive mechanism appears to be an alternative way to regulate membrane
      fluidity when growth is inhibited, e.g. by high concentrations of toxic
      substances. The cis-trans isomerase (Cti) activity is constitutively present and
      is located in the periplasma, it requires neither ATP nor any other cofactor such
      as NAD(P)H or glutathione, and it operates in the absence of de novo synthesis of
      lipids. Its independence from ATP is in agreement with the negative free energy
      of the reaction. cti encodes a polypeptide with an N-terminal hydrophobic signal
      sequence, which is cleaved off during or shortly after the enzyme is transported
      across the cytoplasmic membrane to the periplasmic space. A functional heme
      binding site of the cytochrome c-type was identified in the predicted Cti
      polypeptide and very recently, direct evidence was obtained that isomerization
      does not include a transient saturation of the double bond.

PMID- 14659536
TI  - Improved flagellin genotyping in the Burkholderia cepacia complex.
AB  - Oligonucleotide primers designed to N- and C-terminal sequences of Burkholderia
      cepacia complex fliC genes were used to amplify and sequence fliC genes from a
      strain of Burkholderia vietnamiensis and three isolates of Burkholderia
      multivorans with large fliC genes. Alignments incorporating the new sequences
      enabled the design of polymerase chain reaction (PCR) primers for extension of a
      published PCR/restriction fragment length polymorphism typing method, to include
      isolates that previously failed to yield fliC amplicons. Most B. vietnamiensis
      isolates and hitherto non-typable Burkholderia cenocepacia isolates contained
      much smaller fliC genes than previously reported. Although B. multivorans strains
      with larger fliC genes clustered together, relationships between strains based on
      fliC sequences did not generally correlate with genomovar status.

PMID- 14659537
TI  - The glutamine synthetase of Prevotella bryantii B(1)4 is a family III enzyme
      (GlnN) and glutamine supports growth of mutants lacking glutamate dehydrogenase
      activity.
AB  - Prevotella spp. are believed to play a central role in ruminal nitrogen
      metabolism, but little is understood about the genetics and biochemistry of
      nitrogen assimilation and regulation in these bacteria. The gene encoding a
      family III glutamine synthetase (GSIII, glnN) in Prevotella bryantii B(1)4 was
      cloned by Escherichia coli mutant complementation, and enzyme assays as well as
      Northern blot analysis showed that maximal enzyme activity and glnN transcription
      occurred in cells grown under nitrogen-limiting conditions. Addition of
      methionine sulfoximine (MSX), a GS inhibitor, terminated bacterial growth when
      ammonium was provided as the sole nitrogen source, but the inhibitory effect
      could be overcome by the inclusion of either L-glutamine or trypticase in the
      growth medium. A P. bryantii mutant lacking glutamate dehydrogenase (GdhA)
      activity was isolated by ethylmethylsulfonate mutagenesis. Growth studies with
      different nitrogen sources showed that the mutant strain was still capable of
      growth with ammonium as the sole nitrogen source, albeit at a decreased growth
      rate. The mutant strain could also grow with L-glutamine as a nitrogen source in
      the presence of MSX. These data suggest that GlnN provides an effective route of
      ammonium assimilation for P. bryantii, in addition to that afforded by the
      glutamate dehydrogenase pathway.

PMID- 14659538
TI  - Phylogenetic analysis of fiber-associated rumen bacterial community and PCR
      detection of uncultured bacteria.
AB  - The fiber-associated rumen bacterial community was phylogenetically examined by
      analysis of 16S rRNA gene (16S rDNA) sequences. Hay stems of orchardgrass and
      alfalfa were incubated for 6 and 20 h, respectively in the rumen of two different
      sheep, and total DNA was extracted from the incubated stems to clone bacterial
      16S rDNAs using polymerase chain reaction (PCR). Of 91 such clones, 21 showed
      more than 97% sequence similarity with known isolates, 32 clones had 90-97%
      similarity with known sequences, and for the remaining 38 clones, the similarity
      was less than 90%. The majority of clones fell into the Cytophaga-Flavobacter
      Bacteroides and low G+C Gram-positive bacterial phyla (43 and 44%, respectively).
      Prevotella-related and Butyrivibrio fibrisolvens-related sequences formed large
      clusters in the phylogenetic tree. Unknown sequences were found to form three
      unique clusters, one of which was suggested by semi-quantitative PCR to be more
      prevalent in the rumen receiving a high alfalfa diet.

PMID- 14659539
TI  - Purification and characterization of an aldehyde oxidase from Pseudomonas sp. KY
      4690.
AB  - An aldehyde oxidase, which oxidizes various aliphatic and aromatic aldehydes
      using O(2) as an electron acceptor, was purified from the cell-free extracts of
      Pseudomonas sp. KY 4690, a soil isolate, to an electrophoretically homogeneous
      state. The purified enzyme had a molecular mass of 132 kDa and consisted of three
      non-identical subunits with molecular masses of 88, 39, and 18 kDa. The
      absorption spectrum of the purified enzyme showed characteristics of an enzyme
      belonging to the xanthine oxidase family. The enzyme contained 0.89 mol of flavin
      adenine dinucleotide, 1.0 mol of molybdenum, 3.6 mol of acid-labile sulfur, and
      0.90 mol of 5'-CMP per mol of enzyme protein, on the basis of its molecular mass
      of 145 kDa. Molecular oxygen served as the sole electron acceptor. These results
      suggest that aldehyde oxidase from Pseudomonas sp. KY 4690 is a new member of the
      xanthine oxidase family and might contain 1 mol of molybdenum-molybdpterin
      cytosine dinucleotide, 1 mol of flavin adenine dinucleotide, and 2 mol of [2Fe
      2S] clusters per mol of enzyme protein. The enzyme showed high reaction rates
      toward various aliphatic and aromatic aldehydes and high thermostability.

PMID- 14659540
TI  - Mice immunization with live lactococci displaying a surface anchored HPV-16 E7
      oncoprotein.
AB  - E7 oncoprotein of human papillomavirus-16 (HPV-16) is constitutively produced in
      cervical cancer (CxCa) and is a good candidate for the design of therapeutic
      vaccines. In this work, the nisin-controlled expression system was used to
      display the E7 protein at the cell surface of the food-grade Gram-positive
      bacterium Lactococcus lactis. An efficient cell wall anchoring of E7 was
      obtained. Intranasal administration of these recombinant lactococci in mice
      induced an HPV-16 E7-specific immune response. This is the first report of E7
      cell wall anchoring in L. lactis and represents one more step towards the use of
      live food-grade bacteria to fight against CxCa.

PMID- 14659541
TI  - The cyanobiont in an Azolla fern is neither Anabaena nor Nostoc.
AB  - The cyanobacterial symbionts in the fern Azolla have generally been ascribed to
      either the Anabaena or Nostoc genera. By using comparisons of the sequences of
      the phycocyanin intergenic spacer and a fragment of the 16S rRNA, we found that
      the cyanobiont from an Azolla belongs to neither of these genera.

PMID- 14659542
TI  - Porphyromonas gingivalis 67-kDa fimbriae induced cytokine production and
      osteoclast differentiation utilizing TLR2.
AB  - Porphyromonas gingivalis, a major etiological agent of adult periodontitis, has
      two distinctly different types of fimbriae on the cell surface. The major
      fimbriae, which consist of a 41-kDa fimbrillin of P. gingivalis ATCC 33277, have
      been known to induce inflammatory cytokine production in murine peritoneal
      macrophages. In this study, we examined the effects of the minor fimbriae of P.
      gingivalis, composed of a 67-kDa fimbrillin, on cytokine production in murine
      peritoneal macrophages and the ability to induce osteoclast differentiation.
      Murine peritoneal macrophages were stimulated with P. gingivalis 67-kDa minor
      fimbriae for 24 h, then the levels of interleukin (IL)-1beta, tumor necrosis
      factor (TNF)-alpha and IL-6 production were determined by enzyme-linked
      immunosorbent assay (ELISA). To estimate osteoclast differentiation, mouse
      osteoclast precursors were placed on dentine slices, and cultured with or without
      P. gingivalis 67-kDa minor fimbriae for 7 days. P. gingivalis 67-kDa minor
      fimbriae clearly induced IL-1beta, TNF-alpha and IL-6 production in mouse
      macrophages. Furthermore, pit formations on the dentine slices were significantly
      extended when the osteoclast precursors were incubated with P. gingivalis 67-kDa
      minor fimbriae. Pretreatment with anti-Toll-like receptor 2 (TLR2) antibody
      significantly inhibited IL-1beta, TNF-alpha and IL-6 induction (P<0.05) in mouse
      macrophages and pit-forming activity of osteoclast precursor cells stimulated
      with P. gingivalis 67-kDa minor fimbriae. These results suggest that P.
      gingivalis 67-kDa minor fimbriae may provoke host inflammatory response and be
      involved in periodontal tissue breakdown.

PMID- 14659543
TI  - Functional complementation of E. coli secD and secG mutants by Helicobacter
      pylori homologues.
AB  - The Sec machinery is one mechanism used by bacteria to translocate proteins
      across their cytoplasmic membrane. Most of the Sec components have been
      identified within the important gastric pathogen, Helicobacter pylori, however
      their functionality has not yet been demonstrated. Here we report the existence
      of putative homologues to the Sec components yajC (HP1450) and yidC (HP1551), and
      demonstrate the ability of the H. pylori secD (HP1550) and secG (HP1255)
      homologues to facilitate inner membrane translocation of the maltose-binding
      protein MalE, by complementation of the respective secretion-deficient
      Escherichia coli mutants, thus providing evidence of their functionality.

PMID- 14659545
TI  - Transcriptional starts for cytadherence-related operons of Mycoplasma genitalium.
AB  - One mechanism of mycoplasma cytadherence possessed by several mycoplasmas,
      including Mycoplasma genitalium, necessitates coordination of multiple adhesins
      and adherence-associated proteins. The genes encoding these adherence-related
      proteins are located in three different regions of the M. genitalium genome and
      exhibit an operon-like organization with surrounding genes. To understand whether
      genes encoding adherence-related proteins in M. genitalium are regulated as
      operons, we performed transcriptional and reverse transcription-polymerase chain
      reaction (RT-PCR) analyses on the loci mg191 (encoding major cytadhesin P140
      localized at the specialized tip organelle) and mg218 (encoding high molecular
      mass cytadherence-related protein MG218 required for tip-mediated adherence).
      Primer extension suggested that transcription of mg191 was under the control of
      two transcriptional starts, one immediately upstream of mg191 (Prm(MG191)) and
      the other upstream of mg190 (Prm(MG190)). In contrast, mg218 appeared to be
      transcribed by a single transcriptional start, located upstream of mg217. RT-PCR
      indicated that transcription was continuous from mg190 to mg192 and mg217 to
      mg219, suggesting that these loci constitute true operons. Additional data
      revealed heretofore undetected similarities between adherence-related operons of
      M. genitalium and Mycoplasma pneumoniae.

PMID- 14659544
TI  - The tyrosine decarboxylase operon of Lactobacillus brevis IOEB 9809:
      characterization and conservation in tyramine-producing bacteria.
AB  - Bacterial genes of tyrosine decarboxylases were recently identified. Here we
      continued the sequencing of the tyrosine decarboxylase locus of Lactobacillus
      brevis IOEB 9809 and determined a total of 7979 bp. The sequence contained four
      complete genes encoding a tyrosyl-tRNA synthetase, the tyrosine decarboxylase, a
      probable tyrosine permease and a Na+/H+ antiporter. Rapid amplification of cDNA
      ends (RACE) was employed to determine the 5'-end of mRNAs containing the tyrosine
      decarboxylase gene. It was located only 34-35 nucleotides upstream of the start
      codon, suggesting that the preceding tyrosyl-tRNA synthetase gene was transcribed
      separately. In contrast, reverse transcription-polymerase chain reactions (RT
      PCRs) carried out with primers designed to amplify regions spanning gene
      junctions showed that some mRNAs contained the four genes. Homology searches
      revealed similar clusters of four genes in the genome sequences of Enterococcus
      faecalis and Enterococcus faecium. Phylogenetic analyses supported the hypothesis
      that these genes evolved all together. These data suggest that bacterial tyrosine
      decarboxylases are encoded in an operon containing four genes.

PMID- 14659546
TI  - A method for the enzymatic synthesis and HPLC purification of the peptidoglycan
      precursor UDP-N-acetylmuramic acid.
AB  - UDP-N-acetylmuramic acid (UDP-MurNAc) is a precursor for peptidoglycan
      biosynthesis in bacteria. A major difficulty in the study of this pathway is that
      UDP-MurNAc is not commercially available. We have developed an enzymatic
      synthesis scheme for UDP-MurNAc using two easily purified Escherichia coli
      polyhistidine tagged peptidoglycan biosynthesis enzymes, MurZ and MurB, followed
      by a single-step purification of UDP-MurNAc by high-performance liquid
      chromatography. The identity of the UDP-MurNAc synthesized by our method was
      confirmed by electrospray ionization mass spectrometry. Furthermore, we show that
      the UDP-MurNAc can support a UDP-MurNAc-L-alanine ligase reaction.

PMID- 14659547
TI  - A Narf-like gene from Cryptosporidium parvum resembles homologues observed in
      aerobic protists and higher eukaryotes.
AB  - Here we report a Narf-like gene from the apicomplexan Cryptosporidium parvum
      (CpNARF). CpNARF is an intronless, single-copy gene of 1680 bp which encodes a
      putative protein of 560 amino acids with a calculated molecular mass of 63.1 kDa.
      This gene contains a single highly conserved N-terminal iron-sulfur cluster ([4Fe
      4S]) binding site, as well as most of the H-cluster conserved residues. Reverse
      transcription polymerase chain reaction analysis indicates that CpNARF is
      expressed by the intracellular stages of C. parvum. Although the function of this
      gene is as yet unknown, phylogenetic analyses suggest that CpNARF belongs to the
      group of NARF-like proteins from aerobic protists and higher eukaryotes, which
      are thought to have had an ancestor in common with [Fe]-hydrogenases.

PMID- 14659548
TI  - A simple and efficient Triton X-100 boiling and chloroform extraction method of
      RNA isolation from Gram-positive and Gram-negative bacteria.
AB  - A fast, reliable, and inexpensive Triton X-100 boiling procedure for RNA
      isolation from both the Gram-positive and Gram-negative bacteria was developed.
      The yield of RNA was 0.2-2 mg per 10 ml bacterial culture. The method was tested
      on Gram-positive and Gram-negative bacteria of eight genera and nine species and
      yielded reproducible results. In parallel experiments, the Qiagen and hot phenol
      extraction methods both yielded RNA that contained contaminating 16S and 23S
      rRNA. The Triton X-100 boiling method reported here yielded RNA that was free
      from 16S and 23S rRNA, contained full-length transcripts and did not require
      additional purification. The presence of specific mRNA in one of the RNA samples
      obtained by this procedure was demonstrated by partial amplification of a 732 bp
      vancomycin resistance gene, vanA, by reverse transcription-polymerase chain
      reaction (RT-PCR). The presence of a full-length transcript (1031 bases) of the
      vanA gene was verified by Northern hybridization and probing with a digoxigenin
      (DIG)-labeled vanA PCR partial product. The method provides a rapid, reliable,
      and simple tool for the isolation of good quality RNA suitable for various
      molecular biology experiments.

PMID- 14659549
TI  - Gene transfer into Clostridium difficile CD630 and characterisation of its
      methylase genes.
AB  - Ignorance of pathogenesis in Clostridium difficile may be attributable to a lack
      of effective genetic tools. We have now shown that oriT-based shuttle vectors may
      be conjugated from Escherichia coli donors to the C. difficile strain CD630, at
      frequencies of around 10(-6) transconjugants per donor cell. Transfer is
      unaffected by either sequences present on the vector or its methylation status.
      Whilst the genome of this strain carries five methylase genes, there is no in
      silico or experimental evidence for cognate restriction enzymes. It would seem
      that the identified methylases do not participate in restriction-modification,
      and must, therefore, fulfil another role. A similar situation most likely applies
      to other clostridia.

PMID- 14659550
TI  - Expression of green fluorescent protein in Bacillus brevis under the control of a
      novel constitutive promoter F1 and insertion mutagenesis of F1 in Escherichia
      coli DH5alpha.
AB  - The constitutive expression vector pHY300-F1gfp was constructed to test the
      function of a promoter, F1, cloned from the rice epiphyte Bacillus brevis strain
      DX01. The DX01 cells harboring the plasmid pHY300-F1gfp were shown to produce
      bright green fluorescence. The results were confirmed by Western blot analysis
      and fluorescence-activated cell sorting. Expression of the F1 promoter was
      constitutive. To improve the activity of F1, insertion mutagenesis of F1 based on
      in vitro transposition reaction was performed. Seven mutants with enhanced
      transcription activity in Escherichia coli DH5alpha were obtained. The enhanced
      promoters showed similar high activities in B. brevis strain DX01.

PMID- 14659551
TI  - Construction of vectors for inducible gene expression in Lactobacillus sakei and
      L plantarum.
AB  - We have constructed vectors for inducible expression of genes in Lactobacillus
      sakei and Lactobacillus plantarum. The key elements of these vectors are a
      regulatable promoter involved in the production of the bacteriocins sakacin A and
      sakacin P and the genes encoding the cognate histidine protein kinase and
      response regulator that are necessary to activate this promoter upon induction by
      a peptide pheromone. The vectors are built up of cassettes that permit easy
      exchange of all parts through restriction enzyme digestion and ligation. Using
      beta-glucuronidase as a reporter enzyme, variants of these vectors were compared
      with each other, and with a corresponding system based on genes involved in the
      production of nisin. Several of the new vectors permitted tightly controlled and
      efficient expression of beta-glucuronidase in both L. sakei and L. plantarum.

PMID- 14659552
TI  - Phylogeny of the Glomerales and Diversisporales (fungi: Glomeromycota) from actin
      and elongation factor 1-alpha sequences.
AB  - The arbuscular mycorrhizal (AM) fungi have been elevated to the phylum
      Glomeromycota based on a ribosomal gene phylogeny. In order to test this
      phylogeny, we amplified and sequenced small subunit ribosomal RNA (SSUrRNA),
      actin and elongation factor 1 (EF1)-alpha gene fragments from single spores of
      Acaulospora laevis, Glomus caledonium, Gigaspora margarita, and Scutellospora
      dipurpurescens. Sequence variation within and among spores of an isolate was low
      except for SSUrRNA in S. dipurpurescens, and the actin amino acid sequence was
      more conserved than that of EF1-alpha. The AM fungal sequences were more similar
      to one another than to any other fungal group. Joint phylogenetic analysis of the
      actin and EF1-alpha sequences suggested that the sister group to the AM fungi was
      a Zygomycete order, the Mortierellales.

PMID- 14659553
TI  - Microbiological characterization of artisanal Montasio cheese: analysis of its
      indigenous lactic acid bacteria.
AB  - The aim of this study was to investigate the dynamics of the microflora during
      Montasio cheese ripening, with specific reference to some characteristics of
      biotechnological interest. Nine batches of Montasio cheese produced in different
      plants were analyzed. Streptococcus thermophilus was the predominant species
      throughout the whole ripening period of Montasio cheese. Enterococci were also
      frequently present. This microbial group resulted probably from milk, and its
      proportion decreased rapidly during ripening. The most acidifying microbial
      species was S. thermophilus, while the most proteolytic strains belonged to the
      genera Enterococcus. A high degree of phenotypic diversity occurred within the
      microbial species.

PMID- 14659554
TI  - Ribotyping of lactobacilli isolated from spoiled beer.
AB  - Twenty-nine Lactobacillus strains contaminating beers in different Czech
      breweries as well as representative type strains obtained from the Czech
      Collection of Microorganisms were characterized using ribotyping with EcoRI and a
      probe made complementary to 16S and 23S rRNA genes. Biochemical test results
      assigned the 29 strains to the species L. brevis, L. plantarum, L. buchneri and
      L. paracasei subsp. paracasei. Ribotyping separated L. brevis, L. plantarum and
      L. paracasei subsp. paracasei strains into species-specific ribogroups in full
      correspondence with biotyping; L. buchneri strains were split into two
      ribogroups. Characteristic band patterns for each species and even typical bands
      of certain sizes were observed.

PMID- 14659556
TI  - Codon usage bias and A+T content variation in human papillomavirus genomes.
AB  - We analyzed the codon usage bias of eight open reading frames (ORFs) across up to
      79 human papillomavirus (HPV) genotypes from three distinct phylogenetic groups.
      All eight ORFs across HPV genotypes show a strong codon usage bias, amongst
      degenerately encoded amino acids, toward 18 codons mainly with T at the 3rd
      position. For all 18 degenerately encoded amino acids, codon preferences amongst
      human and animal PV ORFs are significantly different from those averaged across
      mammalian genes. Across the HPV types, the L2 ORFs show the highest codon usage
      bias (73.2+/-1.6% and the E4 ORFs the lowest (51.1+/-0.5%), reflecting as similar
      bias in codon 3rd position A+T content (L2: 76.1+/-4.2%; E4: 58.6+/-4.5%). The E4
      ORF, uniquely amongst the HPV ORFs, is G+C rich, while the other ORFs are A+T
      rich. Codon usage bias correlates positively with A+T content at the codon 3rd
      position in the E2, E6, L1 and L2 ORFs, but negatively in the E4 ORFs. A general
      conservation of preferred codon usage across human and non-human PV genotypes
      whether they originate from a same supergroup or not, together with observed
      difference between the preferred codon usage for HPV ORFs and for genes of the
      cells they infect, suggests that specific codon usage bias and A+T content
      variation may somehow increase the replicational fitness of HPVs in mammalian
      epithelial cells, and have practical implications for gene therapy of HPV
      infection.

PMID- 14659557
TI  - Establishment and characterisation of two cDNA-derived strains of classical swine
      fever virus, one highly virulent and one avirulent.
AB  - The virulence of classical swine fever virus (CSFV) strains including established
      laboratory strains as well as field isolates ranges from avirulent to highly
      virulent. Here, we describe the construction and characterisation of two cDNA
      derived CSFV strains, each corresponding to one of these extremes. The
      recombinant virus vEy-37 caused acute disease indistinguishable from that
      provoked by infection with the highly virulent parent strain Eystrup. In
      contrast, vRiems-3, a molecular clone of the CSFV vaccine strain Riems, was
      avirulent and induced protective immunity in pigs. After repeated passage of vEy
      37 in porcine kidney SK-6 cells adaptive mutations in the E(rns) gene were
      observed. The respective reconstructed mutant virus grew to titres that were
      almost 4log units higher when compared to vEy-37. The mutation in the E(rns) gene
      had only a minor effect on the virulence of the virus. The complete genomic
      sequences of the two CSFV strains, Eystrup and Riems, have been deposited in
      GenBank (accession number AF326963 for CSFV Eystrup, AY259122 for CSFV
      Riems/IVI).

PMID- 14659558
TI  - Demonstration of sheep-associated malignant catarrhal fever virions in sheep
      nasal secretions.
AB  - Ovine herpesvirus-2 (OvHV-2) is the causative agent for sheep-associated
      malignant catarrhal fever, which has never been propagated in vitro. Previous
      studies from this laboratory demonstrated significantly high levels of OvHV-2 DNA
      in sheep nasal secretions, suggesting a likely avenue of transmission. In the
      present study, real-time PCR was used to identify sheep experiencing an episode
      of intense OvHV-2 DNA shedding in their nasal secretions. A nuclease-resistance
      assay was used to examine the secretions for the presence of intact cell-free
      enveloped OvHV-2 virions. The results revealed that all nasal secretion samples
      from five selected individuals experiencing intensive shedding events contained
      cell-free OvHV-2 virions. Virions could not be identified in secretion samples
      from 11 OvHV-2 infected sheep that were not experiencing a shedding event. This
      is the first unequivocal demonstration of cell-free OvHV-2 virions. These results
      suggest that OvHV-2 lytic infection occurs in the epithelium of certain tissues
      in the upper respiratory tract of the natural host.

PMID- 14659559
TI  - Measles virus protein interactions in yeast: new findings and caveats.
AB  - Complementary DNA clones of measles virus N, N (S228Q; L229D), Ncore (N1-400),
      Ntail (N401-525), P, PNT (P1-230), PCT (P231-507), L, MEL (L800-2183) and EL
      (L1300-2183) were fused in frame downstream of the Gal4 binding domain (BD) or
      activating domain (AD). All but BD-L, BD-MEL and BD-EL, were detected by western
      blot, with additional C- and/or N-terminal truncated products in the case of BD
      N, and BD-P. BD-P and BD-PNT directly activated the reporter genes, indicating
      that the PNT domain displays transactivating properties. In yeast two-hybrid
      assays, PNT and PCT domains bind to Ncore and Ntail domains, respectively,
      indicating that N and P interact in a head to tail orientation via two
      independent binding sites. BD-N (S228Q; L229D) and AD-N displayed no or poor
      interaction with P proteins possibly because they may not be properly folded. L
      binding site on P lies within the PCT domain, and two PCT binding sites lie
      within the L1-799 and L800-1300 regions. Thus, N to P and P to L protein
      interactions in measles virus shared many features with other related
      Paramyxoviridae. From a human cDNA library, several candidate partners of N
      protein were identified which all reacted with BD-Ncore, and RNA was found to
      bridge the N protein with one partner.

PMID- 14659560
TI  - Characterization of N protein self-association in coronavirus ribonucleoprotein
      complexes.
AB  - Mouse hepatitis virus (MHV) nucleocapsid (N) protein binds to the large, single
      stranded, positive-sense viral genomic RNA to form a helical nucleocapsid
      structure in mature virions. In addition N protein binds the intracellular form
      of the genomic RNA, all of the MHV subgenomic mRNAs, and expressed non-MHV RNA
      transcripts to form ribonucleoprotein (RNP) complexes in infected cells. Among
      the intracellular viral RNP complexes, only the genomic RNP complex is packaged
      into virus particles. The present study demonstrated that N protein in the MHV
      virion nucleocapsid and in the intracellular genome-length RNP complex that bound
      to viral envelope M protein was tightly self-associated such that its association
      was retained even after extensive RNase A-treatment of the RNP complexes. The
      RNase A-resistant tight N protein association in the virion nucleocapsid was not
      mediated by an intermolecular disulfide bridge between N proteins. In contrast, N
      protein association in the majority of the intracellular RNP complexes was
      susceptible to RNase A-treatment. Because the RNP complexes that specifically
      interact with the M protein are selectively packaged into MHV particles, the
      present data suggested that there was a distinct difference between N protein
      association in viral genomic RNP complexes that undergo packaging into virus
      particles and the subgenomic RNP complexes that are not packaged into MHV
      particles.

PMID- 14659561
TI  - A 25 kDa cleavage product of polypyrimidine tract binding protein (PTB) present
      in mouse tissues prevents PTB binding to the 5' untranslated region and inhibits
      translation of hepatitis A virus RNA.
AB  - The 5' untranslated region (5'UTR) of the hepatitis A virus (HAV) genomic RNA
      contains an internal ribosome entry site (IRES) which interacts with various
      cellular proteins and facilitates cap-independent translation. We report the
      interaction of a 25kDa protein (p25), present in certain murine tissues and most
      abundantly in mouse kidney, with the HAV 5'UTR. This protein was found to be a
      cleavage product of the polypyrimidine tract-binding protein (PTB) and competed
      with it for binding to the HAV 5'UTR RNA. The binding site of p25 overlapped with
      the reported binding site of PTB. Exogenous addition of partially purified p25 to
      in vitro translation reactions resulted in the inhibition of HAV IRES-mediated
      translation, which could be rescued by the addition of purified PTB. These
      results suggest that p25 is a cleavage product of PTB which binds to the HAV IRES
      and antagonizes the translation-stimulating activity of PTB. The presence of the
      25kDa cleavage product of PTB may therefore play a role in the inhibition of HAV
      IRES-mediated translation in mouse tissues.

PMID- 14659562
TI  - Introduction of a NIa proteinase cleavage site between the reporter gene and HC
      Pro only partially restores the biological properties of GUS- or GFP-tagged LMV.
AB  - Lettuce mosaic virus (LMV) isolates LMV-E and LMV-0 differ in their virulence on
      lettuce varieties carrying the mo1(2) resistance gene, which reduces viral
      accumulation and blocks the expression of symptoms after infection with avirulent
      isolates such as LMV-0. Previous work had indicated that reporter genes such as
      GUS or GFP affect the biological properties of recombinant LMV isolates in both
      susceptible and resistant lettuce varieties when fused to the N-terminus of the
      viral protein HC-Pro. The impact of the addition of a cleavage site for the NIa
      proteinase between the reporter gene and HC-Pro was evaluated, in an effort to
      recover the full spectrum of the biological properties of parental isolates.
      Symptoms, accumulation, cell-to-cell and long distance movement of the
      recombinant viruses containing the NIa cleavage site were studied in susceptible
      and mo1(2) lettuce varieties. Both LMV-0 and LMV-E recombinant viruses recovered
      the behaviour of their wild-type parent in susceptible plants upon addition of
      the NIa cleavage site. While the recombinant LMV-E modified in this way recovered
      the breaking properties of its wild-type counterpart in mo1(2) plants, similar
      modification of the LMV-0 derived recombinants failed to rescue a severe
      inhibition in systemic accumulation in mo1(2) plants, despite the fact that
      neither cell-to-cell movement nor phloem loading or unloading seemed to be
      severely affected.

PMID- 14659563
TI  - Generation and characterization of an EICP0 null mutant of equine herpesvirus 1.
AB  - The EICP0 gene (gene 63) of equine herpesvirus 1 (EHV-1) encodes an early
      regulatory protein that is a promiscuous trans-activator of all classes of viral
      genes. Bacterial artificial chromosome (BAC) technology and RecE/T cloning were
      employed to delete the EICP0 gene from EHV-1 strain KyA. Polymerase chain
      reaction, Southern blot analysis, and DNA sequencing confirmed the deletion of
      the EICP0 gene and its replacement with a kanamycin resistance gene in mutant
      KyA. Transfection of rabbit kidney cells with the EICP0 mutant genome produced
      infectious virus, indicating that the EICP0 gene is not essential for KyA
      replication in cell culture. Experiments to assess the effect of the EICP0
      deletion on EHV-1 gene programming revealed that mRNA expression of the immediate
      early gene and representative early and late genes as well as the synthesis of
      these viral proteins were reduced as compared to the kinetics of viral mRNA and
      protein synthesis observed for the wild type virus. However, the transition from
      early to late viral gene expression was not prevented or delayed, suggesting that
      the absence of the EICP0 gene did not disrupt the temporal aspects of EHV-1 gene
      regulation. The extracellular virus titer and plaque areas of the EICP0 mutant
      virus KyADeltaEICP0, in which the gp2-encoding gene 71 gene that is absent in the
      KyA BAC was restored, were reduced by 10-fold and 19%, respectively, when
      compared to parental KyA virus; while the titer and plaque areas of mutant
      KyADeltaEICP0Deltagp2 that lacks both the EICP0 gene and gene 71 were reduced
      more than 50-fold and 67%, respectively. The above results show that the EICP0
      gene is dispensable for EHV-1 replication in cell culture, and that the switch
      from early to late viral gene expression for the representative genes examined
      does not require the EICP0 protein, but that the EICP0 protein may be
      structurally required for virus egress and cell-to-cell spread.

PMID- 14659565
TI  - Sleep and social status in captive gelada baboons (Theropithecus gelada).
AB  - Sleep was investigated in 10 captive gelada baboons (Theropithecus gelada),
      belonging to two harem groups by continuous infrared video recording (n = 4
      males, n = 3 females, n = 3 juveniles). The aim was to investigate the relation
      between sleep and social status. Social status was assessed during daytime
      activities, when the two harem groups interacted. Three behavioral states
      (waking, transitional sleep and relaxed sleep) as well as sleep fragmentation
      were scored based on movements and body posture. The individuals belonging to
      each of the harem groups spent most of the night huddled closely together within
      a sleeping cluster. Sleep was considerably fragmented in all adult and sub-adult
      individuals. No relation was found between sleep latency or sleep fragmentation
      and social rank. Total sleep time was 11.4 +/- 0.5 h per night (n = 10) and was
      negatively correlated with age. In the four males sleep duration was unrelated to
      their social rank, whereas both within the females and the juveniles it increased
      with decreasing rank. The amount of relaxed sleep was lower in the dominant males
      and the dominant females compared to the corresponding low-ranking ones. In
      contrast, dominant males had the highest amount of transitional sleep, while in
      the females no rank-association was evident. These results indicate that the high
      ranking geladas engaging less in a relaxed sleeping posture may be maintaining a
      larger degree of alertness that would enable them to react quickly to nocturnal
      dangers.

PMID- 14659564
TI  - Spatial learning in male mice with different levels of aggressiveness: effects of
      housing conditions and nicotine administration.
AB  - The main aim of the present investigation was to evaluate the possible modulation
      of spatial learning ability by housing conditions and level of aggressiveness in
      mice, also testing whether differences in locomotion and anxiety could influence
      this relationship. Additionally, we have examined effects of nicotine in the
      acquisition and retention of a spatial learning task in groups of mice differing
      in these variables. NMRI male mice were either group-housed or individually
      housed for 30 days and then classified into mice with short (SAL) and long (LAL)
      attack latency after a pre-screening agonistic encounter. Locomotor activity and
      baseline levels of anxiety of these groups were evaluated in the actimeter and
      elevated plus-maze. Results indicated that SAL and LAL individually housed mice
      displayed higher locomotion activity than LAL group-housed mice. In the plus-maze
      test, SAL and LAL individually housed mice showed more total and open arm entries
      than group-housed LAL mice, confirming the hyperactivity of individually housed
      mice and suggesting that isolation had no clear anxiolytic or anxiogenic actions.
      In the water-maze, we compared the performance of individually housed SAL,
      individually housed LAL mice, and group-housed LAL mice treated with nicotine
      (0.35 and 0.175 mg/kg) or vehicle. Nicotine did not improve acquisition in group
      housed mice and even impaired it in individually housed mice. Retention of
      platform position was better in vehicle-treated individually housed mice in
      comparison with vehicle-treated group-housed mice. The present study demonstrates
      that housing conditions but not level of aggressiveness modify spontaneous
      locomotor activity and behaviors displayed on the elevated plus-maze test, and
      can also influence retention of a spatial learning task.

PMID- 14659566
TI  - Age-dependent effects of moderate chronic ethanol administration on different
      forms of memory expression in mice.
AB  - A large number of studies have investigated the effects of chronic ethanol
      administration (CEA) on performance in different types of learning and memory
      tasks in adult rodents. As a general rule, CEA has been reported to impair
      performance, although this depends both on the condition of administration (e.g.
      duration, presence or not of a withdrawn period) and on task demands (e.g.
      spatial versus non-spatial). Indeed, either no impairment or even a facilitation
      of performance have been reported following CEA. However, no study has directly
      addressed the issue as to whether the effect of CEA depends on the age of
      subjects. In this study, C57Bl/6 mice of two age ranges (i.e. 2-3- and 16-18
      month-old) were given either a solution of ethanol (12% v/v) as their only source
      of fluid for 5 months (experimental groups) or were pair-fed with an isocaloric
      solution of dextri-maltose (control groups). Then, they were submitted to a place
      discrimination task in an 8-arm radial maze. Additionally, mice were tested for
      long-term retention following a 21-day interval. Confirming our previous
      findings, the results showed that, with respect to adults (7-8-month-old at the
      time of testing), aged mice (21-23-month-old) of the control group displayed
      impaired relational memory but not procedural memory performance. Further they
      exhibited a higher level of forgetting than adults over the 21-day interval. In
      the same paradigm, CEA resulted in an overall attenuation of both type of deficit
      in aged subjects without altering their procedural memory. Furthermore these
      ethanol-consuming aged mice displayed significantly less levels of forgetting
      than their age-matched controls. Conversely, in the adult group, CEA resulted in
      an overall, although, somewhat less selective impairment of relational memory
      with respect to procedural memory but had no effect on long-term forgetting.
      While confirming the deleterious effect of CEA on learning and memory processes
      in adults, our present findings provide evidence that CEA can selectively
      ameliorate certain cognitive deficits normally associated with ageing.

PMID- 14659567
TI  - Mice deficient for the close homologue of the neural adhesion cell L1 (CHL1)
      display alterations in emotional reactivity and motor coordination.
AB  - Motor and cognitive phenotypes were assessed in mice deficient for the close
      homologue of the L1 adhesion molecule (CHL1). The CHL1-deficient mice displayed
      signs of decreased stress and a modification of exploratory behaviour. The mice
      also showed motor impairments on the Rotarod, but they were able to move as fast
      as controls in the alleys of a T-maze. The observed changes were assumed to be
      related to a deficit in attention. In addition, gender differences in CHL1
      deficits were found and are discussed in view of a possible interaction with
      other cell adhesion molecules (CAMs) during development. The results are
      discussed in relation with motor and cognitive deficits in the human, caused by
      mutations of the distal part of the chromosome 3 which contains the CHL1
      orthologue.

PMID- 14659568
TI  - Intra-accumbens protein kinase C inhibitor NPC 15437 blocks amphetamine-produced
      conditioned place preference in rats.
AB  - In a previous study, intracerebroventricular calcium-dependent protein kinase
      (PKC) inhibition attenuated cocaine place conditioning. This suggested the
      hypothesis that intra-nucleus accumbens (NAc) injections of the PKC inhibitor NPC
      15437 may block place conditioning produced by NAc injections of amphetamine. An
      unbiased conditioned place preference paradigm was employed to evaluate the
      present hypothesis. Thus, during pre-conditioning rats had access to an apparatus
      consisting of two chambers connected by a tunnel for three 15-min sessions.
      During 8 conditioning days with the tunnel blocked, one chamber was paired with
      NAc injections of drug for four 30-min sessions alternating with pairing of the
      other chamber with NAc injections of saline. Time spent on the drug-paired side
      was assessed in a final drug-free test session and compared to the amount of time
      spent there in pre-conditioning; a significant increase was defined as a place
      preference. Intra-NAc amphetamine (20.0 microg/0.5 microl/side) produced a place
      preference. This effect was blocked dose dependently by NPC 15437 (0.1, 0.5 and
      1.0 microg/0.5 microl/side). NPC 15437 (1.0 microg) alone did not produce a place
      preference or aversion. None of the doses of NPC 15437 affected the locomotor
      stimulant effect of intra-NAc amphetamine during conditioning revealing a
      dissociation between the locomotor stimulating and rewarding effects of intra-NAc
      amphetamine. Results implicate PKC in the NAc in reward-related learning. More
      work is needed to elucidate the signaling pathways involved in this type of
      learning.

PMID- 14659569
TI  - Performance of different mouse strains in an object recognition task.
AB  - In the present study, we tested the memory performance of different mouse strains
      (129/Sv, BALB/c, C57BL and Swiss) in an object recognition task. In this one
      trial learning task, mice showed a good object memory performance when a 1-h
      delay was interposed between the first and second trial. However, when a 24-h
      delay was used, the mice did not discriminate between the novel and the familiar
      object in the second trial, indicating that the mice did not remember the object,
      which was presented in the first trial. Using a 4-h delay, the discrimination
      performance was at an intermediate level, suggesting a delay-dependent forgetting
      in this task. Although strain differences were found in the absolute level of
      exploration activity, no strain differences were found on the relative
      discrimination index (d2). The present data show that object memory can be
      assessed in mice and, in contrast to other memory tasks, appears to be less
      strain-dependent. The reliability of the discrimination measures is discussed.

PMID- 14659570
TI  - Low doses of corticotropin-releasing hormone injected into the dorsal raphe
      nucleus block the behavioral consequences of uncontrollable stress.
AB  - The behavioral consequences of uncontrollable stress that are collectively called
      learned helplessness (LH) are mediated in part by increased levels of serotonin
      (5-HT) activity in the dorsal raphe nucleus (DRN) and it's projection regions.
      Recently, corticotropin-releasing hormone (CRH) within the DRN has been
      implicated in the development of LH because intra-DRN CRH produces LH at very
      high doses, and because intra-DRN antagonists for the CRH 2 receptor (CRHR2)
      block LH. Since these behavioral effects are mediated by both 5-HT excitation and
      CRHR2 activation, we have suggested that CRHR2 mediates excitation of DRN 5-HT
      neurons. However, CRH has been shown to inhibit DRN 5-HT neurons at low doses
      that are expected to bind to CRHR1. Since CRHR1 antagonists were ineffective in
      blocking LH, we have further suggested that CRHR1 might mediate the inhibition of
      DRN 5-HT neurons. In support of this hypothesis, although low doses of CRH that
      preferentially bind CRHR1 inhibit DRN 5-HT activity, higher doses at which CRH
      would be expected to bind both receptor subtypes no longer inhibit DRN 5-HT. In
      addition, high doses of CRH are required to produce LH, which is known to be
      mediated by 5-HT excitation, and the CRHR2 agonist urocortin II (UCN II) produces
      LH at much lower doses than does CRH. The present studies show that intra-DRN CRH
      microinjection blocks the behavioral effects produced by DRN UCN II, but only at
      doses that have been shown to inhibit DRN 5-HT activity. Indeed, a higher dose of
      CRH that has been shown to no longer inhibit DRN 5-HT activity did not affect the
      behavioral consequences of DRN UCN II. In a separate experiment, the effective
      dose of CRH blocked the usual behavioral consequences of uncontrollable stress.

PMID- 14659571
TI  - A heparin derived oligosaccharide normalizes the fear response of old Brown
      Norway rats.
AB  - Old animals exhibit impaired spatial learning and an exaggerated response to
      stress. It was predicted that the heparin derived oligosaccharide (HDO), C3,
      would reverse these age-related deficits. Young (4-5 months) and old (19-20
      months) Brown Norway male rats ingested C3 (25 mg/kg per day, p.o.) or vehicle
      (drinking water) daily for 42-44 days. Two weeks after the initiation of drug
      treatment, the rats were examined using a series of behavioral tests. The old
      control rats evidenced: (1) increased neophobia and reduced exploratory behavior
      in a novel open field (OF); and (2) exaggerated freezing during the acquisition
      and retention of a conditioned response (CR) to a Pavlovian light-shock pairing
      ("foreground" conditioning). C3 treatment attenuated or reversed this age-related
      impairment of emotional behavior. Analysis of spatial learning using the Morris
      water maze (MWM), and of CR formation to the place in which the foreground
      conditioning was conducted ("background" conditioning) during context dependent
      fear conditioning (CDFC) did not reveal major age or drug effects on memory
      processes. It is hypothesized that C3 repairs damage to the extracellular matrix
      (ECM) that occurs during the aging process and thereby normalizes age-related
      exacerbated fear behaviors without affecting mnestic processes.

PMID- 14659572
TI  - Neuronal fibrillogenesis: amyloid fibrils from primary neuronal cultures impair
      long-term memory in the crab Chasmagnathus.
AB  - Amyloid beta protein (Abeta) fibrillogenesis is considered one of the crucial
      steps of Alzheimer's disease (AD) pathogenesis. The effect of endogenous neuronal
      amyloid fibrils on memory processes is unknown. To investigate this issue, we
      first characterised the Abeta fibrillar aggregates secreted by cerebellar granule
      cells and then we evaluated the effect of neuronal fibrils on an invertebrate
      model of memory. An increase of fibril formation, assessed by Thioflavin T (ThT)
      fluorescence, was observed in the conditioned medium of apoptotic neurons during
      48 h of the apoptotic process. Moreover, the depolarisation-stimulated secretion
      of cerebellar granule cells contains monomers of endogenous Abeta, which undergo
      cell-free fibrillogenesis over several days of incubation. The pattern of single
      endogenous fibrils, examined by electron microscopy, was similar to that of
      synthetic Abeta while a tighter and more complex interfibrillar organization was
      observed in endogenous fibrils. The biological effect of neuronal fibrils was
      studied in a long-term memory (LTM) paradigm, namely the context-signal learning
      of the crab Chasmagnathus. Pre-training injection of neuronal fibril extract
      (protein concentration, 1 microg/ml) induced amnesia in a dose-dependent manner.
      On the contrary, no effect on retention was observed with the administration of
      two orders higher doses (100 microg/ml) of synthetic Abeta1-40. These results
      indicate that only naturally secreted fibrils, but not synthetic Abeta, clearly
      interfere with memory process.

PMID- 14659573
TI  - Haloperidol and chlorpheniramine interaction in inhibitory avoidance in goldfish.
AB  - The purpose of this study was to investigate a possible interaction between
      histaminergic and dopaminergic systems in learning and memory processes, in an
      inhibitory avoidance test in goldfish. Haloperidol, a dopaminergic antagonist,
      was administrated pre-training and the chlorpheniramine (CPA), a histaminergic
      antagonist, post-training. The inhibitory avoidance procedure was performed in 3
      days, using a rectangular aquarium divided into two compartments (black and
      white), with a central door. On the first day, the animals were habituated for 10
      min. On the second day, they were injected with 2 mg/kg of haloperidol or
      dimethyl sulfoxide (DMSO) 20 min before training. Then, the animals were placed
      in the white compartment, the central door was opened and the time spent for
      crossing between compartments was recorded. After the fish crossed the line
      between compartments a 45 g weight was dropped. This procedure was done five
      times in a row. Immediately after the fifth trial, the fish were injected
      intraperitoneally (i.p.) with either saline or CPA (0.4, 1.0, 4.0, 8.0 or 16
      mg/kg). On the next day (test) the time to cross was recorded again. On the
      training trials, the animals treated with DMSO or haloperidol presented a
      significant increase in the latencies indicating learning (Friedman P = 0.0062
      and 0.0001). The latencies in the test day showed that groups pre-treated with
      haloperidol and treated with CPA presented a dose-dependent increase in
      latencies, and those treated with the 16 mg/kg CPA group showed a significant
      increase (ANOVA two-way followed by Student-Newman-Keuls (SNK) P < 0.01). Thus,
      it can be suggested that the facilitatory action occurs due to an additive
      interaction between both systems, in a dose-dependent way.

PMID- 14659574
TI  - Altered action of dopamine and cholecystokinin on lateral hypothalamic neurons in
      rats raised under different feeding conditions.
AB  - Single-unit activity was recorded in the lateral hypothalamus (LH) of adult
      Wistar rats anaesthetized with urethane. The rats were differently nourished till
      weaning by raising in small (SL), control (CL) or large litters (LL). They gained
      significantly different body weight leading to overweight in SL (mean: 428.4 g on
      day 90) and underweight in LL rats (mean 399.5 g) compared to CLs (414.5 g). The
      mean basal firing rate of LH neurons differed, it was lowest in SL and highest in
      LL rats. The proportion of neurons changing their firing rate by more than 30% in
      response to iontophoretically administered dopamine (DA) was significantly
      greater in SL (76%) than LL rats (54%). Effects of DA were significantly more
      often blocked by a D1 receptor antagonist in LL than CLs. The responsiveness to
      cholecystokinin (CCK) alone and coadministered with DA was also greater in SL
      than LL. Furthermore, the proportion of neurons inhibited by DA alone and in the
      presence of CCK was significantly greater in SL than LL rats. In conclusion,
      litter size and difference in nourishment during early postnatal development of
      rats seem to determine LH basal firing rate. The increased neuronal
      responsiveness to exogenous DA and CCK in neonatally overfed SL rats may indicate
      a decreased activity of these endogenous signals which normally contribute to
      limitation of energy intake.

PMID- 14659575
TI  - A battery of tests for quantitative examination of idiothetic and allothetic
      place navigation modes in humans.
AB  - Research into the neural mechanisms of place navigation in laboratory animals has
      led to the definition of allothetic and idiothetic navigation modes that can be
      examined by quantitative analysis of the generated tracks. In an attempt to use
      this approach in the study of human navigation behavior, 10 young subjects were
      examined in an enclosed arena (2.9 m in diameter, 3 m high) equipped with a
      computerized tracking system. Idiothetic navigation was studied in blindfolded
      subjects performing the following tasks-Simple Homing, Complex Homing and
      Idiothesis Supported by Floor-Related Signals. Allothetic navigation was examined
      in sighted subjects instructed to find in an empty arena the acoustically
      signaled unmarked goal region and later to retrieve its position using tasks
      (Natural Navigation, Cue-Controlled Navigation, Snapshot Memory, Map Reading)
      that evaluated different aspects of allothesis. The results indicate that
      allothetic navigation is more accurate than idiothetic, that the poor accuracy of
      idiothesis is due to angular rather than to distance errors, and that navigation
      performance is best when both allothetic and idiothetic modes contribute to the
      solution of the task. The proposed test battery may contribute to better
      understanding of the navigation disturbances accompanying various neurological
      disorders and to objective evaluation of the results of drug therapy and of
      rehabilitation procedures.

PMID- 14659576
TI  - Impaired delayed spatial win-shift behaviour on the eight arm radial maze
      following excitotoxic lesions of the medial prefrontal cortex in the rat.
AB  - The delayed spatial win-shift (DSWS) radial maze task requires that animals hold
      spatial information for reward location "on-line" both during task performance
      and across a delay. Temporary lidocaine inactivation of anterior cingulate (AC)
      and prelimbic (PL) regions of the rat medial prefrontal cortex (mPFC) has
      revealed dissociable effects on this task, suggesting different roles within
      working memory for each of these areas. However, further research has shown that
      mPFC deficits in the rat may only be transient in nature, particularly on the
      radial maze. The present study was conducted to examine the effects of permanent
      excitotoxic lesions of the mPFC in the DSWS task across repeated trials to assess
      whether change in the degree of impairment would occur over time. Results showed
      that rats with lesions centred on the prelimbic cortex (but with damage extending
      into the anterior cingulate) were impaired on the post-delay test phase of the
      DSWS task. This deficit was characterised by increased errors (both across and
      within phase), earlier error occurrence, and increased latencies. Only the number
      of choices correct before error improved across repeated test days. These results
      are consistent with the involvement of the rat mPFC in spatial working memory and
      response inhibition, supporting previous findings using transient lesions.
      However, the discovery that rats with mPFC lesions learned to delay the intrusion
      of errors into their choice sequence extends previous work, and provides support
      for studies showing that mPFC lesioned rats can improve some aspects of task
      performance given the opportunity to learn over repeated trials.

PMID- 14659577
TI  - Effects of chronic intraventricular infusion of heparin glycosaminoglycan on
      learning and brain acetylcholine parameters in aged rats.
AB  - We reported previously that the glycosaminoglycan heparin (HP) has the facility
      to improve learning in adult rodents when administered into the nucleus basalis
      of the ventral pallidum. Here we gauged the effects of chronic intraventricular
      infusion of HP (20 ng per day over 28 days) in 26-month-old rats in terms of
      Morris water maze performance, habituation to a novel open field, retention of a
      step-through inhibitory avoidance task and changes in forebrain acetylcholine
      (ACh) levels. Control groups included vehicle-infused old and adult (3-month-old)
      rats. The chronic infusion of HP did not significantly influence the performance
      of the old animals in any of the learning and memory tasks employed. HP only
      slightly facilitated the retention of the inhibitory avoidance task and the rate
      of habituation in the open-field paradigm. In the water maze, the
      glycosaminoglycan did not counteract the navigation deficits observed for aged
      controls and even impaired performance during the initial place-learning trials.
      After behavioural testing, tissue levels of ACh were determined in frontal
      cortex, ventral striatum, neostriatum and hippocampus without detecting any
      obvious neurochemical differences between groups. The current results, together
      with our previous work, indicate that HP differentially affects learning and
      memory parameters in adult and aged rats. Thus, whereas the glycosaminoglycan
      proved effective in facilitating mnemonic functions in normal adult animals, no
      such a clear-cut beneficial effect was observed in behaviourally impaired old
      rats.

PMID- 14659578
TI  - Effects of songs and calls on ZENK expression in the auditory telencephalon of
      field- and isolate-reared black capped chickadees.
AB  - We examined the effects of hearing two different conspecific vocalizations on
      expression of the immediate-early gene ZENK in the caudomedial neostriatum (NCM)
      and the caudomedial portion of the ventral hyperstriatum (cmHV) in male and
      female black-capped chickadees (Poecile atricapilla). Both the fee-bee song and
      the chick-a-dee call induced Zenk protein expression in NCM and in cmHV, however,
      patterns of expression to songs and calls varied across brain region. In the
      dorsal region of NCM, fee-bee songs induced more Zenk expression than chick-a-dee
      calls. In ventral NCM and cmHV, Zenk expression did not differ between songs and
      calls. We found that sex of the listener also affected Zenk expression: there was
      more robust ZENK response in males than in females. Finally, we compared field-
      and isolate-reared chickadees and found similar Zenk expression to fee-bee song
      in each group. These findings indicated that the type of conspecific
      vocalization, as well as the sex of the listener, appear to modulate IEG
      expression in the songbird ascending auditory pathway.

PMID- 14659579
TI  - Effects of chronic cocaine on impulsivity: relation to cortical serotonin
      mechanisms.
AB  - Drug addiction can be considered an impulse control disorder in that addicts
      exhibit increased impulsivity on both behavioural and self-report measures. We
      investigated whether chronic cocaine affects delay of gratification and/or
      behavioural disinhibition in rats using the delayed reinforcement and Go/No-go
      paradigms. Animals were treated with saline or cocaine (15 mg/kg) three times per
      day for 14 days; all behavioural tests occurred prior to daily injections. To
      assess the effectiveness of the cocaine treatment, sucrose intake, behavioural
      sensitization and serotonin (5-HT)-dependent (dorsal raphe-stimulated) cortical
      activation were also measured. Chronic cocaine caused a transient (days 7-8)
      increase in impulsivity in the delayed reinforcement paradigm, but did not
      influence behaviour in the Go/No-go paradigm. As expected, chronic cocaine
      increased behavioural sensitization scores, although it did not affect sucrose
      consumption. Although, cocaine treatment did not affect dorsal raphe-stimulated
      electrocorticographic activation, the serotonergic receptor antagonist
      methiothepin (0.1 mg/kg) was more effective in blocking cortical activation in
      cocaine- than in saline-treated animals. The electrocorticographic changes may be
      the result of a pre-synaptic 5-HT deficit and the compensatory supersensitivity
      of post-synaptic 5-HT receptors. Given the differential time courses of the
      behavioural and electrocorticographic data, however, this change probably does
      not mediate the effects of chronic cocaine in the delayed reinforcement paradigm.

PMID- 14659580
TI  - Further evidence for the mediation of both subtypes of dopamine D1/D2 receptors
      and cerebral neuropeptide Y (NPY) in amphetamine-induced appetite suppression.
AB  - Amphetamine (AMPH) is known as an anorectic agent. Repeated treatments of AMPH
      for several days induced a marked anorexia on day 1 followed by a gradual return
      of food intake to normal level. Previously, using daily food intake (DFI) as an
      indicator, we found that both dopamine (DA) D1 and D2 receptors were involved in
      AMPH anorexia. In the present study, using DFI and body weight change (BWC) as
      indicators, we took a further step to examine whether repeated co-administrations
      of D1 and D2 agonists might produce an AMPH-like action. Results revealed that
      repeated co-administrations of D1 and D2 agonists, but not D1 or D2 agonist
      alone, produced an AMPH-like action (i.e., tolerant DFI and BWC), confirming the
      previous study. In addition, we examined whether cerebral neuropeptide Y (NPY),
      an orexigenic neurotransmitter reported to mediate AMPH anorexia, was involved in
      the anorectic action of D1/D2 co-administration. Our result revealed that
      injection of NPY antisense into brain could modify the anorectic action of
      repeated D1/D2 agonists, indicating the involvement of NPY. Taken together, the
      present results confirmed that both subtypes of D1 and D2 receptors and cerebral
      NPY were involved in the anorectic action of AMPH.

PMID- 14659581
TI  - Antipanic procedures reduce the strychnine-facilitated wild running of rats.
AB  - Wild running (WR) behavior of rats seen in response to intense acoustic
      stimulation of audiogenic seizure-paradigm is very similar to the panic flight
      and can be facilitated by subconvulsive doses of strychnine. The present work
      aimed to test whether antipanic procedures, such as dorsal periaqueductal gray
      (dPAG) lesion and imipramine treatments, affect the strychnine-facilitated WR. In
      study 1, six Wistar male adult rats with electrolytic lesion of dPAG had their WR
      completely blocked, whereas it was facilitated in 50% of sham-lesioned control
      rats by a dose of 0.5 mg/kg of strychnine administered intraperitoneal. This
      effect was not reproduced with a higher strychnine dose (1.0 mg/kg). In study 2,
      the effects of imipramine were investigated by testing 36 rats under a dose of
      strychnine that induces WR in 50% of subjects. They were assigned into three
      experimental groups: imipramine treatments of 5.0 and 10.0 mg/kg, and infusions
      of saline. All these treatments were subchronical with three intraperitoneal
      injections within 24 h. Imipramine (10.0 mg/kg) reduced the incidence of WR in
      comparison to the saline results. It is concluded that strychnine-facilitated WR
      is reduced by antipanic procedures and, therefore, can be viewed as a
      manifestation closely related to panic.

PMID- 14659582
TI  - Alteration in behavioral sensitivity to amphetamine after treatment with
      oxotremorine. Effect of dose and test environment.
AB  - Our earlier experiment revealed that rats pretreated once with an
      anticholinesterase develop hyposensitivity to amphetamine (AMPH). One of the
      likely causes of this effect might be a transient hyperexcitation of the central
      muscarinic receptors. It has appeared, however, that rats pretreated with
      oxotremorine (OX), a muscarinic agonist, show an augmented behavioral response to
      AMPH weeks later. The present experiments were performed in order to obtain more
      information on the relationship between the OX-induced sensitization to AMPH and
      the OX dose and dosing regime (single or repeated), and to find out whether the
      environment associated with the acute effects of OX could affect the response to
      AMPH. In experiment 1, adult male rats were given a single i.p. injection of OX
      in home cages at a moderate (0.5 mg/kg) or high (1.0 mg/kg) dose. In experiment
      2, the rats received eight 1.0 mg/kg doses of OX in the course of three days.
      After each injection, some animals returned to their home cages, and some were
      placed in the test cages for 30 min. In both experiments, the response to AMPH
      was assessed on day 21 after the treatment. The obtained results indicate that:
      (i) a single i.p. exposure to OX results in an increase of the rat's behavioral
      sensitivity to AMPH but the moderate dose is more effective in inducing this
      effect; (ii) repeated exposure to OX at high doses, in a regime enabling
      development of tolerance to the acute OX effects, does not alter the rat
      sensitivity to AMPH, and (iii) expression of the AMPH response is suppressed in
      environment which has been associated with acute effects of OX.

PMID- 14659583
TI  - Evidence for a 5-HT2A receptor mode of action in the anxiolytic-like properties
      of DOI in mice.
AB  - DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] displays a high
      affinity for the rat 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi 7.3, 7.4 and 7.8,
      respectively) and acts as an agonist. DOI (0.5-4 mg/kg, i.p. 30 min pre-test)
      increased the number of punished passages in the mouse four plates test (FPT).
      The anti-punishment action of DOI (1 mg/kg, i.p. 30 min pre-test) was abolished
      by prior treatment with the selective 5-HT2A receptor antagonist SR 46949B (0.1
      and 1 mg/kg, i.p. 45 min pre-test) but not by the selective 5-HT2C receptor
      antagonist RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor the selective 5
      HT2C/2B receptor antagonist SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). An
      anxiolytic-like action was also observed for DOI (1 mg/kg) in the elevated plus
      maze (EPM). The anxiolytic-like action of DOI (1 mg/kg, i.p. 30 min pre-test) was
      antagonised by pre-treatment with SR 46949B (0.125 and 0.5 mg/kg, i.p. 45 min pre
      test) but not by RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor SB 206553
      (0.1 and 1 mg/kg, i.p. 45 min pre-test). In conclusion, DOI produced an
      anxiolytic-like profile in the mouse FPT and EPM. These effects are likely to be
      5-HT2A receptor mediated.

PMID- 14659584
TI  - Antipanic-like effect of serotonin reuptake inhibitors in the elevated T-maze.
AB  - There has been an increasing interest in the development of animal models that
      address different types of anxiety disorders. The elevated T-maze (ETM) was
      developed based on the assumption that inhibitory avoidance and one-way escape
      are respectively related to generalized anxiety (GAD) and panic disorder (PD).
      Although anxiolytic effects on the inhibitory avoidance task have been shown for
      drugs used in clinical settings to treat GAD, positive effects of antipanic drugs
      in one-way escape have been described only for imipramine. The study extends the
      pharmacological validation of the ETM to other serotonin reuptake inhibitors that
      have antipanic properties. To this end, we investigated the effects of acute and
      chronic (21 days) IP administration of clomipramine (3, 10 and 30 mg/kg) and
      fluoxetine (5, 10 and 15 mg/kg). Buspirone (0.3, 1 and 3 mg/kg) was used as a
      negative control since the drug is effective in GAD but not PD. Chronically, both
      clomipramine and fluoxetine impaired one-escape, an antipanic-like effect, not
      altering avoidance latencies. Clomipramine, but not fluoxetine, also affected
      locomotion. Acute injection of buspirone impaired avoidance, an anxiolytic-like
      effect. Neither acute nor chronic buspirone altered one-escape. These results
      corroborate the suggestion that one-way escape is related to PD.

PMID- 14659585
TI  - Sleep after differing amounts of conditioned fear training in BALB/cJ mice.
AB  - Shock training and auditory cues associated with shock produce alterations in
      sleep that can be long-lasting in BALB/cJ (C) mice. We examined sleep in C mice
      after different amounts of shock training, and after cues with different strength
      cue-shock associations. Mice were implanted with transmitters for determining
      sleep via telemetry. After baseline sleep recording, the mice were trained
      (between 08:00 and 09:00 h) to associate a cue (tone) with footshock in either
      single shock training (SST: a single tone-shock pairing) or multiple shock
      training (MST: 15 tone-shock pairings) conditions. For testing, the mice were
      presented 15 cues (tone only) in their home cage between 10:45 and 11:00 h on
      post-training days 6, 13, 20, 27, and 34 (Cue 1 to Cue 5) following shock
      training. Sleep was recorded for two days after shock training or cue
      presentation. A separate group of mice received 15 tone-shock pairings and had
      their sleep recorded for 10 consecutive uninterrupted days. Both SST and MST mice
      showed decreases in rapid eye movement sleep (REM) after shock training, with the
      larger effect in the MST mice. Only MST mice showed significant reductions in REM
      in response to the fearful cues, and longer-term alterations in sleep could be
      observed even on the day after cue presentation. These results indicate that
      reminders of an aversive event can impact sleep for prolonged periods, and that
      the degree of the impact varies with amount of training.

PMID- 14659586
TI  - Behavioral effects of intraventricular injections of low doses of ethanol,
      acetaldehyde, and acetate in rats: studies with low and high rate operant
      schedules.
AB  - Although ethanol is typically classed as a sedative-hypnotic, low doses of
      ethanol have been shown to stimulate locomotor activity in mice. However, in rats
      the typical response to peripheral administration of ethanol is a dose-dependent
      suppression of motor activity and operant responding. The present study was
      undertaken to determine the effects of intraventricular (ICV) infusions of
      ethanol, acetaldehyde, and acetate on operant performance in rats. ICV injections
      of ethanol, acetaldehyde, or acetate were given to rats previously trained on
      either a differential-reinforcement-of-low-rates-of-responding (DRL) 30-s
      schedule, which generates low rates of responding, or a fixed ratio 5 (FR5)
      schedule, which generates relatively high rates. Ethanol, acetaldehyde, and
      acetate all produced a rate-increasing effect in rats on the DRL 30-s schedule at
      moderate doses (2.8 and 1.4 micromol, respectively). Acetate also produced a rate
      decreasing effect on the DRL 30-s schedule at a larger dose (8.8 micromol).
      Performance on the FR5 schedule was unaltered by ethanol and acetaldehyde, even
      at doses as high as 17.6 micromol. However, acetate produced a rate-decreasing
      effect on the FR5 schedule at doses of 4.4, 5.6, and 8.8 micromol. Central
      administration of low doses of ethanol and its metabolites can increase operant
      responding on some schedules in rats. Acetate is the substance that is most
      potent for producing rate-suppressing effects. These results indicate that the
      major metabolites of ethanol are pharmacologically active when injected into the
      brain, and suggest that acetate may mediate some of the rate-suppressing effects
      of ethanol, such as sedation, ataxia or motor slowing.

PMID- 14659587
TI  - Motor effects of amphetamine in rats pretreated with either dizocilpine or
      phencyclidine.
AB  - The aim of the present study was to examine motor effects of amphetamine (AMPH)
      in rats pretreated with either dizocilpine (MK-801) or phencyclidine (PCP), and
      to estimate possible differences in these effects. Our results showed that AMPH
      increases the duration of motor effects of PCP, while it does not change motor
      effects of MK-801. These findings may reflect different mechanisms of action of
      MK-801 and PCP, as well as selective influence of AMPH on metabolism of these
      drugs.

PMID- 14659588
TI  - Aging, cancer and nutrition: the DNA methylation connection.
AB  - Cancer and aging are two coupled developmental processes as reflected by the
      higher incidence of cancer in the elderly human population group. Genetic
      mutations accumulate in somatic cells with age, which may explain in part the
      association of age with cancer. Epigenetic mechanisms are also frequently
      involved in controlling gene functions during development and tumorigenesis. A
      common molecular feature associated with both aging and tumorigenesis is global
      hypomethylation of the genomic DNA. The contributing mechanisms underlying this
      hypomethylation are not yet well understood. Epigenetic investigation of cancer
      and aging has recently emerged as a fruitful area of study and has added exciting
      insights into some of the mysteries surrounding aging and cancer. Recent studies
      have also shown that dietary factors can modulate DNA methylation and thereby
      contribute to aging and tumorigenesis. Thus, DNA methylation provides an
      important common link between aging, cancer and nutrition.

PMID- 14659589
TI  - Ageing-apoptosis relation in murine spleen.
AB  - Relatively few studies have been published with regard to modification of
      apoptosis in normal tissues as a function of ageing. The majority of these
      studies demonstrated an increase in programmed cell death (PCD) with age.
      However, opposite results, namely loss of apoptotic control with age, have also
      been reported. In the present study, we examined proliferation and apoptotic cell
      death in spleens of C57/BL mice of different ages. A tendency towards decrease in
      cell proliferative capacity was seen with age. By contrast, apoptosis was
      increased in spleens from aged animals. Moreover, the proliferative
      cell/apoptotic cell ratio decreased in function of age. Ladder type DNA
      degradation was much more pronounced in DNA derived from splenocytes of old mice.
      These results were supported by a decrease of Bcl-2 and an increase in Fas
      receptor expression as well as by increased activation of caspases 8, 3 and 9 in
      splenocytes from aged animals. In addition, cell surface molecular markers
      recognizable by macrophages in apoptotic cells, namely decreased sialic acid
      concomitant with increased unmasking of galactose residues, were more pronounced
      on splenocytes from old mice than on those from young animals. In addition to the
      experimental evidence which supports a role of apoptotic cell death in ageing, a
      series of theoretical reasoning, which could also favor this possibility, are
      discussed.

PMID- 14659590
TI  - Growth hormone administration to long-living dwarf mice alters multiple
      components of the antioxidative defense system.
AB  - Endocrine hormones are thought to be involved in processes that contribute to
      aging. Long-living dwarf mice are growth hormone (GH)-deficient and exhibit
      enhanced expression of antioxidative defense molecules when compared to normal,
      wild type littermates. In this study, 3- and 12-month-old Ames dwarf mice
      received with 50 microg GH or saline for 7 days. Tissues were collected and
      assayed for several antioxidant molecules. In addition to increased body and
      liver weights, GH treatment of dwarf mice decreased liver, kidney and heart
      catalase protein (P < 0.05). Catalase activity was significantly decreased in
      kidney and heart tissues of mice receiving GH compared to dwarf mice treated with
      saline. Glutathione peroxidase (GPX) protein was significantly reduced in liver,
      kidney and muscle of GH-treated mice (P < or = 0.03). Likewise, the activity of
      GPX was decreased in liver and kidney tissues following GH administration (P< or
      = 0.04). Exogenous GH increased glutathione levels in brain, muscle and liver (P<
      or = 0.03) compared to saline controls. This evidence, along with previous data,
      suggests that GH suppresses key components of systems that counter oxidative
      stress. Reductions in GH and IGF-1 signaling contribute to extended life spans in
      a variety of species, which may be partially explained by an increased ability to
      neutralize deleterious byproducts of metabolism.

PMID- 14659591
TI  - HDTIC-1 and HDTIC-2, two compounds extracted from Astragali Radix, delay
      replicative senescence of human diploid fibroblasts.
AB  - Astragalus membranceus (Fish) Bunge Var. mongholicus (Bge) Hsiao is a Chinese
      herb considered as an effective traditional anti-ageing material. The two isomers
      of 4-hydroxy-5-hydroxymethyl-[1,3]dioxolan-2,6'-spirane-5',6',7',8'-tetrahydro
      indolizine-3'-carbaldehyde (HDTIC), HDTIC-1 and HDTIC-2, were extracted from the
      herb. We chose them to investigate their effects on replicative senescence in
      vitro. In this study, we observed the effects of HDTIC-1 and HDTIC-2 on
      morphology, replicative lifespan, and specific markers related to replicative
      senescence in human fetal lung diploid fibroblast (2BS cell). Results have shown
      that both the HDTIC-1 and HDTIC-2 maintain non-senescent phenotype of 2BS cells
      even at late population doubling (PD) and increase cumulative population
      doublings (CPDs) by at least 15-20PDs. The senescence-associated-galactosidase
      (SA-beta-gal) positive cell rates of late PD cells grown from early PD in medium
      containing HDTIC, were much lower than that of late PD control cells, and similar
      to that of young cells. HDTIC also improved cell growth and proliferation and
      promoted the entry of 2BS cells from G0 or G1 phase to S-phase. In addition, the
      advanced glycation end product (AGE) levels of late PD cells grown from early PD
      in DMEM containing HDTIC decreased significantly compared with those of late PD
      control cells. Taken together, the results strongly suggest that both the HDTIC-1
      and HDTIC-2 delay replicative senescence of 2BS cells, and indicate that the
      senescence-delaying effect of HDTIC appears to be due to its many biological
      properties including its potentials of proliferation improvement, inhibitory
      effect of AGE formation, and its antioxidant activity. The differences of optimum
      concentrations of HDTIC-1 (0.1 microM) and HDTIC-2 (1.0 microM) for delaying
      senescence also indicate that the structure of HDTIC may be very sensitive to its
      activity.

PMID- 14659592
TI  - The age-associated decline in the intestinal uptake of glucose is not accompanied
      by changes in the mRNA or protein abundance of SGLT1.
AB  - Studies performed using human and animal models offer conflicting results
      regarding the effect of age on nutrient absorption. The objectives of this study
      were to determine (1) the effects of aging on the in vitro uptake of glucose in
      rats; and (2) the molecular mechanisms of these age-associated changes. Male
      Fischer 344 rats aged 1, 9 and 24 months were fed a standard laboratory diet (PMI
      # 5001). The uptake of 14C-labelled D-glucose was determined in vitro using the
      intestinal sheet method. Northern blotting, Western blotting and
      immunohistochemistry were used to determine the effects of age on the BBM sodium
      dependent glucose transporter, SGLT1, and the BLM Na+K(+)-ATPase. When expressed
      on the basis of intestinal weight, mucosal weight or surface area, there was a
      reduction in glucose uptake in the 24-month-old animals. SGLT1, GLUT2 and Na+K(+)
      ATPase mRNA and protein abundance did not parallel the changes seen in glucose
      uptake. These results indicate that (1) age reduces in vitro intestinal glucose
      uptake in the rat; and (2) this age-associated decline in glucose uptake was not
      explained by alterations in SGLT1, GLUT2 or Na+K(+)-ATPase.

PMID- 14659593
TI  - Effects of aging on mortality, hypothermia, and cytokine induction in mice with
      endotoxemia or sepsis.
AB  - Aging is accompanied by an altered stress response that underlies increased
      susceptibility of the elderly patients to physiological stress such as infection
      and sepsis. In the present study, we investigated the effects of aging on
      mortality, hypothermia, and cytokine induction in mouse models of intra-abdominal
      sepsis and endotoxemia. Systemic inflammation associated with either cecal
      ligation/puncture (CLP) or injection with bacterial endotoxin, lipopolysaccharide
      (LPS), resulted in a significantly elevated mortality rate in aged (24 months)
      compared to young (4 months) mice. The aged mice also showed profound hypothermia
      during these inflammatory stresses; the severity of hypothermia at the early
      phase of sepsis or endotoxemia could predict the mortality of individual animals.
      The stress-mediated induction of interleukin-1beta, interleukin-6, and
      interleukin-10 (IL-1beta, IL-6, and IL-10) in the circulating blood tended to be
      higher with aging in both CLP and LPS models, and in particular, the induction of
      IL-6 was significantly augmented with aging. The serum level of IL-6 showed a
      strong correlation with degrees of hypothermia. In the heart and lungs, the
      induction of mRNA for IL-6 and IL-10 was also significantly enhanced with aging.
      These results clearly demonstrate an age-associated increase in mortality,
      hypothermia, and induction of IL-6 during endotoxemia and sepsis.

PMID- 14659594
TI  - Biodemographic trajectories of age-specific reproliferation from stationary phase
      in the yeast Saccharomyces cerevisiae seem multiphasic.
AB  - Ageing is usually seen as a monotonic decline of functions and survival. However,
      recent studies reported that age-specific mortality rates increased and then
      leveled off or even declined at later ages in several species including humans.
      Preliminary data using the yeast, Saccharomyces cerevisiae, demonstrated an even
      more complicated, non-monotonic pattern of reproliferation after stationary phase
      (i.e. the ability of a cell to exit stationary phase and form a colony). In the
      present article, we conducted a study of the age-specific reproliferation rates
      of yeast populations. Stationary phase yeast cells were maintained in water and
      the reproliferation rates were estimated by the number of yeast able to exit
      stationary phase on rich growth media. We showed that the age-specific
      reproliferation rates in yeast seem to rise, fall and rise again. Furthermore, we
      observed this pattern in different experiments and in different genotypes and
      established that this pattern was not due to genetic heterogeneity of the
      populations.

PMID- 14659595
TI  - ENU-induced late-onset night blindness associated with rod photoreceptor cell
      degeneration in zebrafish.
AB  - We describe a dominant mutation, night blindness d (nbd), that causes late-onset
      rod photoreceptor cell degeneration in zebrafish. The mutation was induced by
      treating male zebrafish with N-ethyl-N-nitrosourea (ENU). Visual sensitivity was
      tested using a behavioral assay based on a visually mediated escape response. At
      a young age, the heterozygous (nbd+/-) fish did not show any signs of night
      blindness or retinal degeneration. At 2 years, their behaviorally assessed visual
      sensitivity was decreased, albeit no alterations in the electroretinogram (ERG)
      were detected. Histology revealed that in the mutant retinas the rod
      photoreceptor cell outer segments (ROS) were thinned out. In homozygous larvae
      (nbd-/-), mass neural degeneration was detectable at about 2 days post
      fertilization (dpf). They died at an early age, usually no later than 8 dpf. In
      conclusion, nbd is a dominant mutation that causes late-onset night blindness
      with slow progression. However, nbd is not photoreceptor cell-specific, as
      becomes clear from the systemic dysfunctions of the homozygous larvae.

PMID- 14659596
TI  - Werner syndrome and its protein: clinical, cellular and molecular advances.

PMID- 14659598
TI  - Outcome from severe accidental hypothermia in Southern Finland--a 10-year review.
AB  - The charts of all adult patients with accidental hypothermia who were admitted to
      a single academic hospital during a 10 year period were retrospectively
      retrieved. The aim was to identify factors associated with survival of those with
      hypothermic cardiac arrest. Of 75 admitted patients, 44 were found to be
      haemodynamically stable and not to require invasive rewarming measures. Of the
      remaining 31 patients, 23 were in refractory cardiac arrest due to primary
      hypothermia and rewarmed using cardiopulmonary bypass (CPB). The aetiology of
      hypothermia was immersion in cold water in 48%, exposure to cold environment in
      39% and submersion in 13% of these patients. Their median age was 50 years, and
      83% were males. The patients received a total of 70 min of conventional CPR
      before institution of CPB. Fourteen of these patients (61%) survived to discharge
      from hospital. Factors associated with survival were age (P=0.015), arterial pH
      (P=0.011), PaCO2 (P=0.003), and serum potassium (P=0.007). Logistic regression
      analysis showed that of the 23 patients, 22 could be correctly classified as
      survivor or nonsurvivor based on the level of serum potassium and arterial pCO2.
      It is concluded that patients with cardiac arrest due to primary hypothermia
      tolerate long periods of conventional CPR before institution of CPB. The possible
      predictive role of serum potassium and arterial pCO2 needs further evaluation.

PMID- 14659599
TI  - Reliability of the Cardiff Test of basic life support and automated external
      defibrillation version 3.1.
AB  - The introduction of the European Resuscitation Guidelines (2000) for
      cardiopulmonary resuscitation (CPR) and automated external defibrillation (AED)
      prompted the development of an up-to-date and reliable method of assessing the
      quality of performance of CPR in combination with the use of an AED. The Cardiff
      Test of basic life support (BLS) and AED version 3.1 was developed to meet this
      need and uses standardised checklists to retrospectively evaluate performance
      from analyses of video recordings and data drawn from a laptop computer attached
      to a training manikin. This paper reports the inter- and intra-observer
      reliability of this test. Data used to assess reliability were obtained from an
      investigation of CPR and AED skill acquisition in a lay responder AED training
      programme. Six observers were recruited to evaluate performance in 33 data sets,
      repeating their evaluation after a minimum interval of 3 weeks. More than 70% of
      the 42 variables considered in this study had a kappa score of 0.70 or above for
      inter-observer reliability or were drawn from computer data and therefore not
      subject to evaluator variability. 85% of the 42 variables had kappa scores for
      intra-observer reliability of 0.70 or above or were drawn from computer data. The
      standard deviations for inter- and intra-observer measures of time to first shock
      were 11.6 and 7.7 s, respectively. The inter- and intra-observer reliability for
      the majority of the variables in the Cardiff Test of BLS and AED version 3.1 is
      satisfactory. However, reliability is less acceptable with respect to shaking
      when checking for responsiveness, initial check/clearing of the airway, checks
      for signs of circulation, time to first shock and performance of interventions in
      the correct sequence. Further research is required to determine if modifications
      to the method of assessing these variables can increase reliability.

PMID- 14659600
TI  - Emergency echocardiography to detect pericardial effusion in patients in PEA and
      near-PEA states.
AB  - OBJECTIVES: Emergency echocardiography (EM echo) has been proposed to assist in
      decision-making in patients with pulseless electric activity (PEA) or PEA-like
      states. We observed the value of EM echo by emergency physicians in detecting
      pericardial effusion in patients in PEA and near PEA states. MATERIALS AND
      METHODS: Observational, prospective series at a Level 1 urban ED of patients with
      non-traumatic PEA or near PEA states who had EM echoes performed by emergency
      physicians during an 18-month period. Outcomes of patients with EM echoes were
      established by review of clinical course, formal echocardiography, radiography,
      operation or autopsy. RESULTS: Twenty patients had EM echo for non-traumatic
      hemodynamic collapse. Eight of 20 patients (40%) were without cardiac ventricular
      motion and were refractory to ACLS measures. Twelve of 20 (60%) patients had
      cardiac kinetic motion observed on echo. Eight of the 12 (67%) patients with
      cardiac motion had a pericardial effusion observed on EM echo. Formal
      echocardiography or other imaging studies confirmed all pericardial effusion
      cases. The following diagnoses were subsequently confirmed in patients with
      pericardial effusion: one aortic aneurysm, two aortic dissections, two metastatic
      cancers, one post-dialysis effusion, two minimal effusions. Three patients had
      tamponade with emergency pericardial drainage or surgery. In two of four patients
      with cardiac activity without pericardial effusion, EM echo was useful by
      detecting pacer capture and ROSC, respectively. CONCLUSIONS: Emergency
      echocardiography performed by emergency physicians in patients in PEA or near PEA
      states can detect pericardial effusions with correctable etiologies versus true
      PEA with ventricular standstill.

PMID- 14659601
TI  - A multiple logistic regression analysis of in-hospital factors related to
      survival at six months in patients resuscitated from out-of-hospital ventricular
      fibrillation.
AB  - INTRODUCTION: The impact of the immediate in-hospital post-resuscitation care
      after out-hospital cardiac arrest is not well known. Based on treatment variables
      and laboratory findings a multiple logistic regression model was created for the
      prediction of survival at 6 months from the event. MATERIALS AND METHODS: A
      retrospective study of the hospital charts of patients successfully resuscitated
      and treated in one of three community hospitals from 1998 to 2000. In addition to
      several pre-hospital variables, the mean 72 h values of clinical features such as
      blood pressure, blood glucose concentration and initiated treatment used, were
      included in a forward multiple logistic regression model predicting survival at 6
      months from the event. RESULTS: The charts of 98 out of a total of 102 patients
      were sufficiently complete and included in the analysis. Variables independently
      associated with survival were age, delay before a return of spontaneous
      circulation, mean blood glucose and serum potassium, and the use of beta-blocking
      agents during post-resuscitation care. When those patients who were assigned a
      'do not attempt to resuscitate' (DNAR) order during the first 72 h of treatment
      were excluded from the analysis blood glucose, blood potassium and the use beta
      blocking agents remained independently associated with survival. CONCLUSION: This
      study suggests that in-hospital factors are associated with survival from out-of
      hospital cardiac arrest. The mean blood glucose and serum potassium during the
      first 72 h of treatment and the use of beta-blocking agents were significantly
      and independently associated with survival.

PMID- 14659602
TI  - Incidence and survival rate of bystander-witnessed out-of-hospital cardiac arrest
      with cardiac etiology in Osaka, Japan: a population-based study according to the
      Utstein style.
AB  - PURPOSE: To clarify the incidence and survival rate of bystander-witnessed out-of
      hospital cardiac arrests (OHCA) with cardiac etiology in Osaka Prefecture, Japan,
      with a population of nearly 9 million according to the Utstein style. SUBJECTS
      AND METHODS: 5047 consecutive OHCA cases were treated by ambulance personnel
      during the 12-month period starting since 1 May 1998. 974 cases were considered
      to be bystander-witnessed OHCA with cardiac etiology and analyzed using the
      Utstein style. RESULTS: Of the 974 cases (100%), 50 cases (5.1%) survived after 1
      month and 28 (2.9%) of them after 1 year. The Ventricular fibrillation
      (VF)/ventricular tachycardia (VT) group comprised 164 (16.8%) cases and there
      were statistically differences between the two groups as below (the VF/VT group
      vs. the non-VF/VT group): gender (male: 76.8 vs. 60.7%), age (61.7+/-14.7 vs.
      68.7+/-17.1), history of ischemic heart disease (IHD) (30.5 vs. 15.3%),
      performance rate of bystander cardiopulmonary resuscitation (CPR) (34.1 vs.
      21.4%) and time interval between receipt of an emergency call and arrival at the
      scene (5.5+/-2.9 vs. 6.0+/-2.9 min). CONCLUSION: The incidence of bystander
      witnessed (OHCA) with cardiac etiology and VF or VT were remarkably low compared
      with those reported by other studies conducted in some areas of Europe or the
      USA.

PMID- 14659603
TI  - Comparison of standard CPR versus diffuse and stacked hand position interposed
      abdominal compression-CPR in a swine model.
AB  - Interposed abdominal compression cardiopulmonary resuscitation (IAC-CPR) is an
      innovative basic life support technique requiring no mechanical adjuncts.
      Optimizing its performance remains a challenge. Hand-position technique over the
      abdomen during interposed abdominal compression (IAC) may be important. The
      purpose of this study was to determine if there is a difference in efficacy
      depending on the type of abdominal hand-position used. Two different hand
      positions were studied: open hands, placed side by side, resulting in diffuse
      abdominal compression and stacked hands, with one on top of the other, producing
      a more focal compression of the abdomen. Thirty swine were cannulated with
      micromanometer-tipped pressure transducers in the ascending aorta (Ao) and right
      atrium (RA), and Millar Doppler-tipped catheters in the descending aorta and
      inferior vena cava (IVC) to determine flow patterns during cardiopulmonary
      resuscitation (CPR), During CPR there were no differences in aortic systolic or
      right atrial systolic pressures. Both forms of IAC-CPR produced greater aortic
      diastolic and right atrial diastolic pressures then standard CPR (STD-CPR)
      (P<0.05). Coronary perfusion pressures (CPP), however, were not different. Blood
      flow directions and velocity patterns showed that STD-CPR chest compressions
      produce caudally directed blood flow in both the descending aorta and the IVC,
      and that such flows reverse (becoming cranially directed) during the relaxation
      phase of chest compression. IAC-CPR produced similar blood flow patterns in the
      aorta and IVC, as seen with STD-CPR. There were no differences in blood flow
      patterns between the different forms of IAC-CPR. No CPR-produced trauma
      difference was found. Abdominal hand position (diffuse or stacked) did not affect
      blood flow in either the aorta or IVC or resuscitation success in this
      experimental model. There was a trend towards better outcomes with stacked hands
      IAC-CPR with 90 versus 70% survival with STD-CPR.

PMID- 14659605
TI  - Compared to angiotensin II, epinephrine is associated with high myocardial blood
      flow following return of spontaneous circulation after cardiac arrest.
AB  - INTRODUCTION: Epinephrine (adrenaline) and vasopressin are used currently to
      improve myocardial blood flow (MBF) during cardiac arrest. Angiotensin II has
      also been shown to improve MBF during CPR. We explored the effects of angiotensin
      II or epinephrine alone, and the combination of angiotensin with epinephrine, on
      myocardial and cerebral blood flows in a swine model of cardiac arrest. METHODS:
      Swine were instrumented for regional blood flow measurements. Ventricular
      fibrillation was induced and CPR begun. Angiotensin II 50 mcg/kg (ANG),
      epinephrine 0.02 mg/kg (EPI) or the combination (ANG+EPI) was administered. Blood
      flow was measured during baseline normal sinus rhythm (NSR), before (CPR) and
      after drug administration (CPR+DRUG), and post reperfusion return of spontaneous
      circulation (ROSC). RESULTS: All groups had a significant increase in MBF during
      CPR following drug administration (P<0.05). [table: see text] There was a trend
      toward higher flows in the EPI groups. The group receiving both EPI and ANG did
      not have higher blood flows than the EPI or ANG alone groups. Both groups that
      received EPI had markedly elevated MBF following ROSC compared with angiotensin
      II (P<0.05). CONCLUSIONS: The combination of ANG and EPI did not improve MBF
      during cardiac arrest. Epinephrine may increase MBF compared with angiotensin II
      post-reperfusion.

PMID- 14659604
TI  - The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free
      radical generation and degrades left ventricular function after myocardial
      ischemia-reperfusion.
AB  - BACKGROUND: During reperfusion of ischemic myocardium nitric oxide (NO) reacts
      with superoxide radicals to form cardiotoxic peroxynitrite, which causes lipid
      peroxidation. Our hypothesis was that infusion of a NO donor S-nitroso-N
      acetylpenicillamine (SNAP) during ischemia-reperfusion would exacerbate the
      oxidative damage to the myocardium by increased formation of nitrogen radicals.
      METHODS AND RESULTS: In 19 open-chest dogs, left anterior descending (LAD)
      coronary occlusion (15 min)-reperfusion (15 min) sequences were created. Using
      electron paramagnetic resonance (EPR), we monitored the coronary sinus
      concentration of ascorbate free radical (Ascz*-), a measure of free radical
      generation (total oxidative flux). Seven control dogs (Group 1) received
      intravenous saline infusion during occlusion-reperfusion, while 12 dogs received
      SNAP infusion (Group 2: 2.5 microg/min per kg SNAP, and Group 3: 5 microg/min per
      kg SNAP). Left ventricular fractional area shortening was determined by
      echocardiography. Dogs in Group 3 receiving a high dose of SNAP (5 microg/min per
      kg) demonstrated a higher Ascz*- concentration increase than the control group.
      Percent fractional area shortening in Group 1 declined from 77+/-4.0 (baseline)
      to 54+/-9.0% during ischemia (P<0.05), and then fully recovered to 74+/-3.7% with
      reperfusion. In the SNAP-treated dogs, the percent fractional area shortening
      during reperfusion was significantly lower than baseline in Group 2 (55+/-3.9 vs.
      baseline 74+/-4.4%, P<0.05) and in Group 3 (49+/-5.0 vs. baseline 71+/-4.5%,
      P<0.01). In five additional dogs, nitrotyrosine immunohistochemistry showed heavy
      staining of the ischemic-reperfused myocardium. CONCLUSIONS: The NO donor SNAP
      increased free radical concentration and exacerbated myocardial oxidative damage
      after ischemia-reperfusion.

PMID- 14659606
TI  - Calcium channel blocker overdose mimicking an acute myocardial infarction.
AB  - A 42-year-old man presented with shortness of breath, weakness, and diaphoresis,
      and developed a new left bundle branch block while under evaluation in the
      Emergency Department. At emergency cardiac catheterization, he was found to have
      only insignificant coronary disease, and a hyperdynamic ventricle. Despite these
      findings, he subsequently developed profound bradycardia and hypotension, which
      were refractory to standard therapies including pressors, calcium, and
      transvenous pacing. He gradually improved over several days and made a full
      recovery, after which he admitted to taking multiple calcium channel blockers
      (CCBs) in an attempt to self-medicate for symptoms he related to his lifelong
      paroxysmal supraventricular tachycardia. This is the first report of a CCB
      overdose mimicking an acute myocardial infarction, and highlights the fact that
      CCB overdose must be considered in the differential diagnosis of some patients
      who present with apparent acute myocardial infarction.

PMID- 14659607
TI  - Predictions from misleading pig model are potentially harmful to humans.

PMID- 14659609
TI  - [Peritoneum and laparoscopy: the revolution is ahead!].

PMID- 14659610
TI  - [Hyperthermic chemotherapy for peritoneal primary and gastrointestinal
      carcinomatoses].
AB  - Peritoneal carcinomatosis should no longer be considered as an automatically
      terminal disease in abdominal cancer patients. The aim of this comprehensive
      review of the literature was to evaluate the indications and contraindications of
      intraperitoneal hyperthermic chemotherapy with extensive cytoreduction surgery.
      Several aspects of the procedure are detailed. Feasibility, short-term and
      survival results are analysed owing to a comprehensive review of published
      studies.

PMID- 14659611
TI  - [Abdominal lavage for peritoneal cancer cell seeding prevention].
AB  - Spontaneous or iatrogenous peritoneal seeding is responsible for locoregional
      recurrent cancer or peritoneal carcinomatosis. Few surgeons are used to wash the
      abdominal cavity to prevent peritoneal seeding. But experimentally, washing is
      not able to dislodge or destroy tumour cells adherent to the peritoneum or to the
      surgical wounds. The antitumoral effect of abdominal washing is increased by
      addition of antiseptics or anti-adherent agents.

PMID- 14659612
TI  - [Management of duodenal adenomatosis in patients with familial adenomatous
      polyposis].
AB  - AIM OF THE STUDY: To review our global management of duodenal adenomas in
      patients with familial adenomatous polyposis and report the results of different
      therapeutic approaches. To present the outcome and possible sequels of
      pancreaticoduodenectomy. PATIENTS AND METHODS: We identified five cases of
      duodenal adenomas in patients with familial adenomatous polyposis over a period
      of 10 years (1992-2001), we followed the progression of their Spigelman score.
      Results of conservative and surgical treatment were collected. RESULTS: Duodenal
      adenomas were discovered 5-33 years after the first operation for colonic
      polyposis. The score of Spigelman was as follows: 2, stage 2; 3, stage 3; 1,
      stage 4. Endoscopic laser therapy followed by Sulindac prescription was proposed
      in three cases, with only one success. Duodenopancreatectomy was performed in
      four patients: once the diagnosis of adenoma was made in one patient, due to
      Spigelman stage 4 with severe dysplasia, because development of intramucosal
      carcinoma under surveillance in one patient, and after failure or complication of
      conservative treatment in two others. Worsening of Spigelman score was observed
      in two out of four patients submitted to conservative therapy. Correlation
      between Spigelman score and final examination of the specimen was correct in two
      cases. There was neither significant morbidity nor long-term nutritional sequel
      after pancreaticoduodenectomy. CONCLUSION: Duodenal adenomas may recur or
      progress into malignant degeneration under conservative treatment. The
      pancreaticoduodenectomy is an acceptable solution for stage 4 of Spigelman,
      especially when severe dysplasia is present.

PMID- 14659613
TI  - [Can the time between interventions be reduced in the operating theater?
      Prospective study].
AB  - BACKGROUND AND AIM OG THE STUDY: The interval between two surgical interventions
      is increasing because of the introduction of successive safety measures. Our aims
      were to prospectively evaluate the different intervals between two elective
      abdominal surgical interventions and to determine which factors were associated
      with a decrease in the inter-operative time delay. MATERIALS AND METHODS: Between
      November 2001 and July 2002, 102 inter-operative periods were prospectively
      analyzed. All the interventions involved either an elective, planned laparotomy
      or a laparoscopic procedure, under general anesthesia. The interval between two
      operations was divided into three periods: the departure of the patient operated
      on; the empty theatre; the entry of the next patient. The collected data were
      compared to retrospective data from 90 days and 10 years prior to the study.
      RESULTS: The average time delay between two interventions was 63.5 min (40-107)
      vs. 72.3 min (30-91) 3 months earlier and 32 min (10-105) (P = 0.001) 10 years
      earlier. The average time from skin closure to the departure of the patient from
      the operating room was 15.7 min (5-35), of which 3.5 min (1-15) was surgically
      related, 7.7 min (1-26) was anesthetic time (waking the patient) and 4.5 min (2
      15) for taking the patient out of theatre. The average duration of the period
      called 'empty theatre' was 13.7 min (7-65), of which 8.9 min (4-15) was for
      cleaning the operating room. Finally, the last period lasted, on average, 32.1
      min (11-69), of which 16.7 min (3-49) was anesthetic time, 2.3 min (2-15) for
      positioning the patient and 9.9 min was surgically related. In this study, the
      shortest time between interventions was 40 min and the longest was 107 min. The
      theoretical shortest time possible (summing the lowest values for each period)
      was 19 min, while the longest (summing the largest values) was 169 min.
      Anesthetic time represented 38% of the entire inter-operative period, while
      surgical time represented 21%. Laparoscopic procedures did not significantly
      effect the inter-operative interval. CONCLUSIONS: Because of the multiple safety
      measures required, the inter-operative delay is continuously increasing and, in
      this study, was equivalent to the actual operative time of the surgical
      procedures. The inter-operative period cannot be shortened below 20 min or so.
      The reduction of this period would only be possible by involving and coordinating
      the different personnel that contribute to performing an operation, by optimizing
      the procedures and by harmonizing materials. The lack of interest and the lack of
      concern for the most efficient use of resources within the public hospitals, as
      well as the recent legal and social constraints introduced in France, are the
      main factors preventing progress in these areas.

PMID- 14659614
TI  - [External ionizing radiation on the prosthesis-arterial anastomosis for the
      prevention of intimal hyperplasia and study of biomechanical resistance.
      Experiments and results].
AB  - PURPOSE: To evaluate the use of external ionizing radiation for the prevention of
      intimal hyperplasia in anastomosis between PTFE and artery. METHODS: Bypass using
      a 6 mm PTFE was performed on a swine subrenal aorta with a distal conventional
      anastomosis (N = 35) associated (test group; N = 17) or not (control group; N =
      18) with post-operative external radiation (20 Gy) on this anastomosis. At 45
      days, histological studies and morphometric studies were performed on the aorta
      receiving the anastomosis. Two protocols were performed, the first protocol with
      standard analysis and the animals were randomly assigned to either group (test
      group; N = 11 and control group; N = 13) and the second protocol with test of
      extraction comparing the biomechanical resistance between the irradiated group (N
      = 6) and the control group (N = 5). RESULTS: Twenty-one animals survived the
      procedure in the first protocol, 11 in the second. The endothelium was restored
      in either group. Histological recasting was observed in the media after radiation
      with fibrosis and areas of necrosis. Intimal thickness was significantly lower
      after irradiation in the heel (P < 0.01), the head (P < 0.01) and the suture line
      (P < 0.001) of the artery in the first protocol. The intimal thickness was also
      significantly lower in the second protocol after radiation in the heel (P < 0.05)
      and the head of the artery (P < 0.05). There was no difference between the two
      groups comparing the resistance. CONCLUSION: After external irradiation, the
      thickness parameter of the intima decreased significantly in comparison with the
      control group with similar resistance. Media fibrosis and necrosis need to be
      confirmed by further investigation.

PMID- 14659615
TI  - [Pancreaticojejunostomy in the treatment of chronic pancreatitis].
AB  - INTRODUCTION: The aim of this retrospective study was to evaluate the immediate
      and long-term outcome of pancreaticojejunostomy (PJ) in the treatment of chronic
      pancreatitis. MATERIAL AND METHODS. - From 1980 to 1997, 140 patients with
      chronic pancreatitis with dilated Wirsung duct were treated by PJ and were
      studied retrospectively. There were 123 men and 17 women, with a mean age of 46
      years (range: 18-79 years). Ongoing alcoholic addiction was present in 116
      patients (83%). Chronic pain uncontrolled by major analgesics was the indication
      of PJ in 126 patients (90%). RESULTS: The mortality rate was 1.4% (n = 2). The
      morbidity rate was 11% (n = 16). Mean hospital stay was 16 days (range: 8-25
      days). The mean follow-up was 7.4 years (range: 2-15 years) in 94 patients.
      Functional results were good or mild in 93% of cases (n = 87). In seven patients
      (7%), the results were bad with persistence of chronic pain requiring major
      analgesics. A mean weight increase of 5.8 kg (range: 1-16 kg) was observed in 74
      patients (79%). Twelve patients (13%) developed de novo diabetes mellitus. In the
      43 patients with preoperative diabetes, 24 patients suffered deterioration of
      their status. No patient recovered from exocrine insufficiency. CONCLUSIONS: In
      case of dilated Wirsung, PJ must be indicated preferentially because of its good
      efficiency on pain relief with low mortality and morbidity rates.

PMID- 14659616
TI  - [Which surgical technique for stage IV haemorrhoids?].

PMID- 14659617
TI  - [A rare cause of intestinal obstruction after laparoscopic colectomy].
AB  - Described here is a case of obstruction of the ileal loop caused by a volvulus
      forming on an internal hernia through the mesenteric opening following left
      laparoscopic-assisted hemicolectomy. The clinical radiologic, pathogenic and
      therapeutic aspects are described with review of the literature.

PMID- 14659618
TI  - [Pulmonary hyalinising granuloma with mediastinal fibrosis: a rare cause of
      dysphagia].
AB  - Pulmonary hyalinising granulomas (PHG) are rare. They are defined by the presence
      of collagen lamellar fibrosis. One third are associated with retroperitoneal or
      mediastinal fibrosis. Two cases of PHG are presented. They were revealed by
      dysphagia due to tight oesophageal stricture from associated mediastinal
      fibrosis. PHG are considered as a benign and slowly evolving disease, but
      associated mediastinal fibrosis may evolve on its own. Only steroid therapy may
      slow down progression. This makes an accurate diagnosis necessary. It relies on
      large surgical biopsies.

PMID- 14659619
TI  - [Rupture of a jejunal artery pseudo-aneurysm after a cephalic
      duodenopancreatectomy].
AB  - Arterial pseudo-aneurysms complicating pancreaticoduodenectomy are rare but have
      a poor prognosis. They usually result from arterial erosion due to pancreatic
      fistula. The authors report a pseudo-aneurysm with an uncommon localization
      (first jejunal artery), diagnosed after a negative first arteriography, and
      successfully treated by radiological embolization. Special features of pseudo
      aneurysms complicating pancreaticoduodenectomy are reviewed.

PMID- 14659620
TI  - [Perineal necrotizing cellulitis disclosing rectal adenocarcinoma].
AB  - We report one case of rectal cancer disclosed by a perineal cellulitis in a
      diabetic woman. This infrequent association has a bad prognosis. Diagnosis is
      mainly clinical. Treatment is urgent with large spectrum antibiotic therapy,
      surgical debridement, colostomy and hyperbaric oxygen if available. Surgical
      treatment of the rectal cancer can be done immediately or delayed.

PMID- 14659621
TI  - [Resection of the retroportal pancreatic lamina during a cephalic
      pancreaticoduodenectomy: first dissection of the superior mesenteric artery].
AB  - We report a modification of the standard resection of the retroportal pancreatic
      lamina during pancreaticoduodenectomy. The resection begins with the dissection
      of the origin of the superior mesenteric artery (SMA) above the left renal vein
      and a step-by-step section of the retroportal pancreatic lamina on the right side
      of the SMA, then the pancreatic head is retracted to the left and freed from the
      portal vein, and lastly the neck of the pancreas is transected. This technique
      allows a total lymph node clearance, secures the dissection of the SMA, and
      allows safe identification of anatomic variations like a replaced right hepatic
      artery originating from the SMA.

PMID- 14659622
TI  - [Histological and cytopathological cancer specimens: good practice in operating
      room].
AB  - Concerning good practice for the management of histological cancer specimen, the
      main recommendations concern: (1) the quality of transmission in information
      between professionals; (2) the necessity of fresh, unfractionated, oriented
      surgical samples; (3) the importance of an appropriate storage condition for
      samples collected for extemporaneous examination, freezing or cell culture; (4)
      the quality of the deep freezer at temperatures of -80 degrees C or liquid
      nitrogen for frozen samples storage; (5) the importance of fixing tissues shortly
      after sample collection in buffered Formal solution in order to prevent cell
      lysis.

PMID- 14659623
TI  - [Best practice guidelines in stomatherapy: a tool for interdisciplinary
      management of stoma patients].

PMID- 14659624
TI  - [Thyroid medullary cancers: persistent hyperthyrocalcitoninemia after surgery.
      Article by C. Proye].

PMID- 14659626
TI  - Peroxidase-catalyzed co-oxidation of 3,3',5,5'-tetramethylbenzidine in the
      presence of substituted phenols and their polydisulfides.
AB  - The steady-state kinetics of the horseradish peroxidase (HRP)-catalyzed oxidation
      of 3,3',5,5'-tetramethylbenzidine (TMB) has been studied in the presence of 2
      amino-4-nitrophenol (ANP), gallic acid (GA) or 4,4'-dihydroxydiphenylsulfone
      (DDS) and their polydisulfides poly(ADSNP), poly(DSGA), poly(DSDDS) at 20 degrees
      C in 10 mM phosphate buffer, pH 6.4, supplemented with 5-10% dimethylformamide.
      The second-order rate constants for the reactions of ANP, GA, poly(DSGA) and
      poly(DSDDS) with HRP-Compound I (k2) and Compound II (k3) have been determined at
      25 degrees C in 10 mM phosphate buffer, pH 6.0 by stopped-flow spectrophotometry.
      ANP, GA and their polydisulfides strongly inhibited HRP-catalyzed TMB oxidation.
      Inhibition constants (Ki) and stoichiometric coefficients of inhibition (f) have
      been determined for these reactions. The most effective inhibitor was poly(DSGA)
      (Ki=1.3 microM, f=35.6). The oxidation of substrate pairs by HRP, i.e., TMB-DDS
      and TMB-poly(DSDDS) at pH 7.2 resulted in a approximately 8- and approximately 12
      fold stimulation of TMB oxidation rates, respectively. The mechanisms of the HRP
      catalyzed co-oxidation of TMB-phenol pairs are discussed.

PMID- 14659627
TI  - Copper selectively triggers beta-sheet assembly of an N-terminally truncated
      amyloid beta-peptide beginning with Glu3.
AB  - Metal ions have been suggested to induce aggregation of amyloid beta-peptide
      (Abeta), which is a key event in Alzheimer's disease. However, direct evidence
      that specific metal-peptide interactions are responsible for the amyloid
      formation has not previously been provided. Here we present the first example of
      the metal-induced amyloid formation by an Abeta fragment, which exhibits a clear
      cut dependence on the amino acid sequence. A heptapeptide, EFRHDSG, corresponding
      to the amino acid residues 3-9 of Abeta (Abeta(3-9)) undergoes a conformational
      transition from irregular to beta-sheet and self-associates into insoluble
      aggregates upon Cu(II) binding. A Raman spectrum analysis of the Cu(II)-Abeta(3
      9) complex and aggregation assays of mutated Abeta(3-9) peptides demonstrated
      that a concerted Cu(II) coordination of the imidazole side chain of His6, the
      carboxyl groups of Glu3 and Asp7, and the amino group at the N-terminus is
      essential for the amyloid formation. Although Abeta(1-9) and Abeta(2-9) also
      contain the metal binding sites, neither of these peptides forms amyloid
      depositions in the presence of Cu(II). The results of this study may not only
      provide new insight into the mechanism of amyloid formation, but also be
      important as a step toward the construction of proteinaceous materials with a
      specific function under the control of Cu(II).

PMID- 14659628
TI  - Synthesis and physic-chemical properties of a copper(II) complex with 2-(2
      pyridyl)iminotetrahydro-1,3-thiazine hydrochloride-water (1/2) (PyTzHCl.2H2O).
      Crystal structure of PyTz and [[CuCl(PyTz)]2(mu-Cl)2].
AB  - The synthesis of 2-(2-pyridyl)iminotetrahydro-1,3-thiazine (PyTz) has been
      carried out, as well as the determination of its X-ray crystal structure,
      together with the coordination behaviour and equilibra study of PyTzHCl.2H2O with
      copper(II) in aqueous solution at 298 K and 0.1 M ionic strength in NaClO4. The
      formation constants are determined and discussed in terms of the characteristics
      of the ligand. The compound Di-mu-chloro-bis[chloro[2-(2-pyrydil-kappaN)amino-5,6
      dihydro-4H-1,3-thiazine-kappaN]copper] has been isolated and its crystal and
      molecular structure determined by X-ray analysis. The structure consists of
      dimeric molecules [Cu2Cl4L2], in which copper ions are bridged by two chloro
      ligands. The geometry about each copper approximates to a distorted square
      pyramid with the bridging ligands occupying apical and equatorial sites of each
      copper ion, while the PyTz ligand and the remaining chloride ion are located in
      an equatorial plane. The compound was also characterized through elemental
      analysis, magnetic susceptibility, electron paramagnetic resonance, and
      electronic and infrared spectroscopies.

PMID- 14659629
TI  - Acid-base properties and copper(II) complexes of dipeptides containing histidine
      and additional chelating bis(imidazol-2-yl) residues.
AB  - Copper(II) complexes of dipeptides of histidine containing additional chelating
      bis(imidazol-2-yl) agent at the C-termini (PheHis-BIMA [N-phenylalanyl-histidyl
      bis(imidazol-2-yl)methylamine] and HisPhe-BIMA [N-histidyl-phenylalanyl
      bis(imidazol-2-yl)methylamine]) were studied by potentiometric, UV-Visible and
      Electron Paramagnetic Resonance (EPR) techniques. The imidazole nitrogen donor
      atoms of the bis(imidazol-2-yl)methyl group are described as the primary metal
      binding sites forming stable mono- and bis(ligand) complexes at acidic pH. The
      formation of a ligand-bridged dinuclear complex [Cu2L2]4+ is detected in
      equimolar solutions of copper(II) and HisPhe-BIMA. The coordination isomers of
      the dinuclear complex are described via the metal binding of the bis(imidazol-2
      yl)methyl, amino-carbonyl and amino-imidazole(His) functions. In the case of the
      copper(II)-PheHis-BIMA system the [NH2, N-(amide), N(Im)] tridentate coordination
      of the ligand is favoured and results in the formation of di- and trinuclear
      complexes [Cu2H(-1)L]3+ and [Cu3H(-2)L2]4+ in equimolar solutions. The presence
      of these coordination modes shifts the formation of "tripeptide-like" ([NH2, N-,
      N-, N(Im)]-coordinated) [CuH(-2)L] complexes into alkaline pH range as compared
      to other dipeptide derivatives of bis(imidazol-2-yl) ligands. Although there are
      different types of imidazoles in these ligands, the deprotonation and
      coordination of the pyrrole-type N(1)H groups does not occur below pH 10.

PMID- 14659630
TI  - Kinetics and equilibria for the formation of a new DNA metal-intercalator: the
      cyclic polyamine Neotrien/copper(II) complex.
AB  - A study has been performed of the kinetics and equilibria involved in complex
      formation between the macrocyclic polyamine 2,5,8,11-tetraaza[12]-[12](2,9)[1,10]
      phenanthrolinophane (Neotrien) and Cu(II) in acidic aqueous solution and ionic
      strength 0.5 M (NaCl), by means of the stopped-flow method and UV
      spectrophotometry. Spectrophotometric titrations and kinetic experiments revealed
      that the binding of Cu(II) to Neotrien gives rise to several 1:1 complexes
      differing in their degree of protonation. Under the experimental hydrogen ion
      concentration range investigated, complexation occurs by two parallel paths: (a)
      M2+ + (H4L)4+ <==> (MH4L)6+ and (b) M2+ + (H3L)3+ <==> (MH3L)5+. The rate
      constants values found for complex formation, by paths (a) and (b), are much
      lower than the values expected from water exchange at copper(II) and other
      amine/Cu(II) complexation kinetic constants. Kinetic experiments at different
      NaCl concentrations indicated that this finding was not due to chloride ion
      competition in complex formation with Neotrien, but it was related to a ring
      rigidity effect. As the phenanthroline moiety could, in principle, interact with
      nucleic acids by intercalation or external binding, some preliminary measurements
      concerned with the possible interactions occurring between the Cu(II)/Neotrien
      complex and calf thymus DNA (CT-DNA) have also been carried out. The absorption
      spectra of the Cu(II)/Neotrien complex change upon addition of CT-DNA at pH 7.0,
      revealing the occurrence of complex-nucleic acid interactions. Moreover,
      fluorescence titrations, carried out by adding the Cu(II)/Neotrien complex to CT
      DNA, previously saturated with ethidium bromide (EB), show that the
      Cu(II)/Neotrien complex is able to displace EB from DNA, suggesting the complex
      is able to intercalate into the polynucleotide and then to cleave the
      phosphodiester bond of DNA.

PMID- 14659631
TI  - Synthesis and DNA interaction studies of a binuclear ruthenium(II) complex with
      2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline as bridging and
      intercalating ligand.
AB  - A novel binuclear complex [(bpy)2Ru(mu-bipp)Ru(bpy)2](ClO4)4, where bpy=2,2'
      bipyridine and bipp=2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10
      phenanthroline has been synthesized. Photophysical results reveal that this
      complex interacts with calf-thymus DNA with intrinsic binding constant 2.6 x
      10(5) M(-1) in the buffer containing 5 mM Tris and 50 mM NaCl. The fact that the
      intraligand transition of bipp around 370 nm decreased by up to 50% in the
      presence of DNA, much more pronounced than the metal to ligand charge transfer
      band around 445 nm indicates the bridging ligand bipp is also the intercalating
      ligand into DNA base pairs. The emission band around at 601 nm increased by 1.4
      fold, and red shifted 14 nm when DNA was added to saturation. The emission
      quenching of this complex by K4[Fe(CN)6] was depressed greatly when DNA was
      present. Viscometric measurements also proved the intercalative binding mode.

PMID- 14659632
TI  - Synthesis and structural characterization of silver(I), aluminium(III) and
      cobalt(II) complexes with 4-isopropyltropolone (hinokitiol) showing noteworthy
      biological activities. Action of silver(I)-oxygen bonding complexes on the
      antimicrobial activities.
AB  - Through two unequivalent oxygen donor atoms of the hinokitiol (Hhino; C10H12O2; 4
      isopropyltropolone) ligand that showed noteworthy biological activities, the
      dimeric, silver(I)-oxygen bonding complex [Ag(hino)]2 1, the monomeric
      aluminium(III) complex [Al(hino)3].0.5H2O 4 and the cobalt(II) complex
      "[Co(hino)2]2.H2O" 6 were synthesized and characterized with elemental analysis,
      thermogravimetric and differential thermal analysis (TG/DTA), FTIR and solution
      (1H and 13C) NMR spectroscopy. The crystal structure of 1 was determined by
      Rietveld analysis based on X-ray powder diffraction (XPD) data and those of
      [Al(hino)3].MeOH 4a and [Co(hino)2(EtOH)]2 6a, being obtained as yellow block
      crystals and red platelet crystals, respectively, by crystallization of 4 and 6,
      were determined by single-crystal X-ray analysis. The antimicrobial activities of
      1, 4 and 6, evaluated with minimum inhibitory concentration (MIC; microg ml(-1)),
      were compared with those of other metal complexes (M=Na, Li, Cs, Ca, V, Zn) with
      the hino- ligand. The antimicrobial activities observed in the alkali-metal salts
      strongly suggested that they were attributed to the effect of the anionic hino-
      species. The antimicrobial activities of 1 were significantly enhanced, whereas
      those of other metal complexes were suppressed, compared with those of the
      neutral Hhino and anionic hino- molecules. The antimicrobial activities observed
      in 1 were comparable with those of other recently found silver(I)-oxygen bonding
      complexes, the ligands of which had no activity. Thus, it is proposed that the
      antimicrobial activities of the silver(I)-oxygen bonding complexes are due to a
      direct interaction or complexation of the silver(I) ion with biological ligands
      such as protein, enzyme and membrane, and the coordinating ligands of the
      silver(I) complexes play the role of a carrier of the silver(I) ion to the
      biological system.

PMID- 14659633
TI  - Might telomerase enzyme be a possible target for trans-Pt(II) complexes?
AB  - Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric DNA
      (TTAGGG) repeats. Previously, we have studied the effect on telomerase enzyme of
      several cis-platinum(II) complexes bearing aromatic amines as bulky carrier
      groups. All these complexes possess cis-geometry, according to the Cleare and
      Hoschele's rule. Since recent reports have dealt with the anti-cancer activity of
      trans-platinum compounds, in this study we have investigated the Farrell's
      prototypical trans-[Pt(Cl)2(pyridine)2], hereafter called trans-PtPy, in order to
      understand whether it may possess any anti-telomerase activity. The trans-PtPy
      has low water solubility and requires dimethyl sulfoxide (DMSO) as co-solvent,
      thus making the biological tests problematic. The effect of trans-PtPy on MCF-7
      cell line concerning log-term telomerase inhibition, telomerase-related gene
      expression, viability, and apoptosis was evaluated. In a cell-free biochemical
      assay, trans-PtPy showed significant and dose-dependent inhibition of semi
      purified telomerase. The bulk of data indicate that trans-PtPy acts as a non
      properly selective anti-proliferative agent, although it shows an initial
      telomerase inhibitory effect. Telomere length reduction seems not to be the main
      mechanism causing the observed cell apoptosis. For comparison purpose, results on
      cis-[Pt(Cl)2(pyridine)2], hereafter cis-PtPy, are reported.

PMID- 14659634
TI  - Study on biological effect of La3+ on Escherichia coli by atomic force
      microscopy.
AB  - The biological effects of rare-earth metal ions on the organism have been studied
      using La3+ as a probe ion and Escherichia coli cell as a target organism. Atomic
      force microscopy (AFM) studies reveal that La3+ substantially changes the
      structure of the outer cell membrane responsible for the cell permeability.
      Significant damages of the outer cell membrane are observed using scanning
      electron microscopy (SEM) after the introduction of La3+. In result, the cell
      becomes easily attacked by lysozyme. Moreover, inductively coupled plasma-mass
      spectrometry (ICP-MS) measurements show considerable amount of Ca2+ and Mg2+ in
      the supernatant from the La3+ exposed cells. It is proposed that La3+ can replace
      Ca2+ from the binding sites because of their close ionic radii and similar ligand
      specificities. Lipopolysaccharide (LPS), which forms the outer membrane of Gram
      negative bacteria, could not serve as the cellular envelope steadily after Ca2+
      and Mg2+ released from their binding sites on the LPS patches.

PMID- 14659635
TI  - Uptake of antitumor platinum(II)-complexes by cancer cells, assayed by
      inductively coupled plasma mass spectrometry (ICP-MS).
AB  - A systematic study on intracellular Pt uptake and Pt accumulation ratio in breast
      cancer MCF-7 cell line has been performed on a number of Pt(II)-complexes, namely
      cisplatin, carboplatin and oxaliplatin, clinically employed as antitumor drugs,
      trans- and cis-[Pt(Cl)2(pyridine)2] and cis-[Pt(Cl)2(pyridine)(5-SO3H
      isoquinoline)] complexes, previously investigated also as potential telomerase
      inhibitors. In particular, long incubation times have been chosen in order to
      understand the fate of the complexes in the cells. For this purpose, sub-acute
      drug concentrations must be employed and, therefore, a very sensitive method of
      analysis like as inductively coupled plasma mass spectrometry (ICP-MS) superior
      to the widely employed atomic absorption spectroscopy (AAS) has been adopted. Any
      relationships among uptake/accumulation and several parameters such as drug
      structure, lipophilicity, drug concentration and incubation time have been sought
      and analyzed: the bulk of data point for a passive diffusion mechanism through
      the cell membrane.

PMID- 14659636
TI  - Electrochemical investigation on interaction between DNA with quercetin and Eu
      Qu3 complex.
AB  - The interactions of quercetin (Qu) and Eu-Qu3 complex with calf thymus DNA were
      studied using cyclic voltammetry (CV) and double potential step chronocoulometry
      (DPSCC) at glass carbon electrode (GCE) for the surface method. The method is
      simple, convenient, reliable, reagent saving. Information such as intrinsic
      binding constant (K), and binding numbers (n) of bound species per DNA (bp),
      ratio (K(Ox)/K(Red)) of the binding constants for the oxidized and reduced forms
      of a bound species and interaction mode was obtained using dsDNA-modified GCE.
      Quercetin and Eu-Qu3 can both bind to DNA, but quercetin binds to DNA mainly by
      electrostatic attraction and the complex bind to DNA by both intercalation and
      electrostatic attraction. For the quercetin/dsDNA-modified GCE systems, a K of
      (3.80+/-0.3) x 10(4) M(-1), saturation coverage value (Gammas) of (2.28+/-0.2) x
      10(-10) mol/cm2 and n of 1.2 were obtained. For the complex system, a saturation
      coverage value (Gammas) of 1.65 x 10(-10) mol/cm2 and n of 1.8 were obtained.

PMID- 14659637
TI  - Effects of the substitution positions of Br group in intercalative ligand on the
      DNA-binding behaviors of Ru(II) polypyridyl complexes.
AB  - Two new polypyridyl ligands containing substituent Br at different positions in
      the phenyl ring, PBIP [PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline],
      OBIP [OBIP=2-(2-bromophenyl)imidazo[4,5-f]1,10-phenanthroline] and their Ru(II)
      complexes, [Ru(phen)2PBIP]2+ 1, [Ru(phen)2OBIP]2+ 2 (phen=1,10-phenanthroline),
      have been synthesized and characterized. The binding strength of the two
      complexes to calf thymus DNA (CT DNA) was investigated with spectrophotometric
      methods, viscosity measurements, as well as equilibrium dialysis and circular
      dichroism spectroscopy. The theoretical calculations for these two complexes were
      also carried out applying the density functional theory (DFT) method. The
      experimental results show that the Br group substituting H at different positions
      of the phenyl ring in the intercalated ligand has significant effects on the
      spectral properties and the DNA-binding behaviors of Ru(II) complexes. Both the
      complexes can bind to CT DNA in intercalative mode and interact with CT DNA
      enantioselectively. Moreover, complex 1 can bind to CT DNA more strongly than
      complex 2, and complex 2 can become a much better candidate as an
      enantioselective binder to CT DNA than complex 1. The theoretical calculations
      show that both intercalative ligands, PBIP and OBIP, in these two complexes are
      essentially planar, and the obtained electronic structures of the complexes can
      be used to explain reasonably some of their experimental regularities or trends.
      Such experimental and theoretical information will be useful in design of novel
      probes of nucleic acid structures.

PMID- 14659638
TI  - Coordination modes vs. antitumor activity: synthesis and antitumor activity of
      novel platinum(II) complexes of N-substituted amino dicarboxylic acids.
AB  - The trans-(+/-)-1,2-diaminocyclohexaneplatinum(II) complexes of multidentate L
      glutamate (Glu) and L-aspartate (Asp) were prepared and their antitumor activity
      was examined in relation with their coordination modes. All these complexes were
      obtained as a mixture of (O,O')- and (O,N)-chelate isomers due to rapid
      isomerization of the initially formed (O,O')-isomer to the thermodynamically more
      stable (O,N)-isomer. The (O,O')/(O,N)-isomeric mixture with the mole ratio of
      80/20 exhibited excellent antitumor activity while the pure (O,N)-isomer was only
      marginally active. Therefore, in order to prevent the linkage isomerization of
      the active (O,O')-isomer to the inactive (O,N)-isomer, we have designed N
      substituted amino dicarboxylic acids as a leaving group and prepared a new series
      of complexes, [Pt(dach)(RGlu)] and [Pt(dach)(RAsp)] (dach=trans-(+/-)-1,2
      diaminocyclohexane; R=acetyl (Ac), propionyl (Pro), pivaloyl (Piv),
      carbobenzyloxy (Cbz) or phthaloyl (Phth)) and characterized by means of elemental
      analyses, and 1H NMR, 195Pt NMR and IR spectroscopies. The N-substituted amino
      dicarboxylate ligands were found to coordinate to platinum(II) ion through only
      the (O,O')-chelation mode, and their Pt(II) complexes were chemically stable in
      aqueous solution. The present Pt(II) complexes of N-substituted amino
      dicarboxylic acids showed excellent antitumor activity against both murine
      leukemia L1210 and human tumor cells. Especially, the highly hydrophobic N
      phthaloylglutamate complex, [Pt(dach)(PhthGlu)], exhibited an outstanding in
      vitro activity (IC50=2.22 microM) on the human stomach cancer cells which are not
      responsive to cisplatin and carboplatin.

PMID- 14659639
TI  - Synthesis and insulinomimetic activities of novel mono- and tetranuclear
      oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid.
AB  - Two chargeless VO(IV) complexes with 3-hydroxypyridine-2-carboxylic acid
      (H2hpic), [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)].3H2O (1) and the cyclic tetramer
      [(VO)4(mu-(hpic-O,O',N))4(H2O)4].8H3O (2), have been synthesized and
      characterized by elemental analysis, mass, infrared, electronic absorption,
      electron spin resonance (ESR) spectroscopies, and X-ray crystallography. Their
      coordination structures are similar to each other (and 1 is readily transformed
      into 2), but are quite different from that of bis(pyridine-2
      carboxylato)oxovanadium(IV). The magnetic susceptibility of 2 indicates the
      presence of a weak ferromagnetic intramolecular interaction between the V atoms
      at low temperature, in addition to a weak antiferromagnetic intermolecular
      interaction. The ESR signal of 2 was broad, while 1 showed an eight-line
      hyperfine splitting pattern due to coupling of the unpaired electron with the 51V
      nucleus (I=7/2). The ESR spectrum and cyclic voltammogram of 2 clearly show that
      the cyclic tetramer remains intact in solution. The insulinomimetic activity of 1
      and 2 was evaluated by means of in vitro measurements of the inhibition of free
      fatty acid release from epinephrine-treated isolated rat adipocytes. While 1
      exerted higher insulinomimetic activity than VOSO4, the activity of 2 was
      significantly lower than that of VOSO4. Hence 2 appears to retain its cyclic
      structure during the in vitro test. These results indicate that the rational
      ligand design for VO complexes might be a promising approach to obtain superior
      insulinomimetic activity.

PMID- 14659640
TI  - Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac
      HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD.
AB  - Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac
      HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD were studied by
      potentiometric and spectroscopic (UV-Vis, CD and EPR) techniques. The results
      reveal that both ligands have effective metal binding sites, but the tripeptide
      is a much stronger complexing agent than the tetrapeptide. The formation of a
      macrochelate via the coordination of the imidazolyl residues is suggested in the
      copper(II)-Ac-HisValHis-NH2 system in the acidic pH range, while a 4N complex
      predominates at physiological pH. The interaction of Ac-HisValHis-NH2 with
      zinc(II) results in the formation of a precipitate indicating polynuclear complex
      formation. Both copper(II)-Ac-HisValHis-NH2 and copper(II)-HisValHis systems
      exhibit catalytic activity toward the dismutation of superoxide anion at
      physiological pH, but the saturated coordination sphere of the metal ions in both
      systems results in low reactivity as compared to the native enzyme.

PMID- 14659641
TI  - Kinetics and mechanism of the reaction between chromium(III) and 3,4
      dihydroxyphenylpropionic (dihydrocaffeic) acid in weak acidic aqueous solutions.
AB  - The reaction of 3,4-dihydroxyphenylpropionic acid (dihydrocaffeic acid, hydcafH3)
      with chromium(III) in weak acidic aqueous solutions has been shown to take place
      through various oxygen-bonded intermediates. The formation of the oxygen-bonded
      complexes upon substitution of water molecules of the chromium(III) coordination
      sphere takes place in at least three stages, the first of which has an observed
      rate constant k1(obs)=k1K0'[hydcafH3]/[H+] where K0' corresponds to the
      Cr(H2O)6(3+) complex dissociation equilibrium. The second and third stages are
      ligand concentration independent and are thus attributed to isomerisation and
      chelation processes. The corresponding activation parameters are DeltaH2(not
      equal)=78+/-3 kJmol(-1), DeltaS2(not equal)=-49+/-9 JK(-1)mol(-1), DeltaH3(not
      equal)=60+/-9 kJmol(-1) and DeltaS3(not equal)=-112+/-39 JK(-1)mol(-1). The
      kinetic results support associative mechanisms and the nature of the electronic
      spectra a catecholic-type of coordination at the pH and concentration range
      studied and reported in this paper. The associatively activated substitution
      processes are accompanied by proton release causing a pH decrease. At lower acid
      concentration oxidation of the ligand takes place with concomitant high increase
      in the UV and VIS absorbance.

PMID- 14659642
TI  - Copper(II) complexes of peptide fragments of the prion protein. Conformation
      changes induced by copper(II) and the binding motif in C-terminal protein region.
AB  - In this paper, we report the characterization of copper(II) complexes with two
      prion (PrP) protein peptide fragment analogues (VNITKQHTVTTTT), one with the N
      terminus acetylated and the C-terminus amidated (PrP Ac180-193NH2) and the other
      with both the C- and N-termini free (PrP 180-193). Such peptide sequence almost
      entirely encompasses the PrPC's helix 2 in the C-terminal region. The
      stoichiometry, the binding modes and the conformational features of the
      copper(II) complexes with the above mentioned two peptides were investigated by
      electrospray ionization-mass spectrometry (ESI-MS), UV-visible (UV-Vis)
      spectrometry and electron paramagnetic resonance (EPR) spectrometry as well as by
      circular dichroism (CD) measurements. The binding site location of copper(II) in
      the structured region of the protein can be here suggested on the basis of our
      findings that show the involvement of His 187 residue. The similarity of the EPR
      parameters suggests that the anchoring imidazole residue drives the copper(II)
      coordination environment towards a common binding motif in different regions of
      the prion protein.

PMID- 14659643
TI  - Effects of solvent composition and ionic strength on the interaction of quinoline
      antimalarials with ferriprotoporphyrin IX.
AB  - Enthalpy-entropy compensation in the interaction of quinoline antimalarials with
      ferriprotoporphyrin IX (Fe(III)PPIX) in 40% aqueous dimethyl sulfoxide (DMSO) has
      been compared with that in pure aqueous solution. The data indicate that the
      degree of desolvation and loss of conformational freedom is virtually identical
      in both systems. Taken together with previous findings showing that the molar
      free energies of association of these drugs with Fe(III)PPIX in both solvent
      systems are very similar, this suggests that the recognition site on the
      metalloporphyrin is comparable in both cases. This is despite the fact that
      Fe(III)PPIX exists as a dimer in aqueous solution, but is monomeric in 40% DMSO.
      Free energies of association of chloroquine, quinine and quinidine with
      Fe(III)PPIX are largely insensitive to the concentration of sodium perchlorate in
      40% DMSO. This demonstrates that electrostatic interactions play only a minor
      role in the overall stability of these complexes under these conditions.
      Increasing DMSO concentration greatly weakens the interactions of chloroquine,
      amodiaquine, quinine, quinidine and 9-epiquinine with Fe(III)PPIX. This suggests
      that hydrophobic interaction plays a major role in the stability of these
      complexes. Further investigation of chloroquine has revealed that the free energy
      of association with Fe(III)PPIX also weakens as a function of decreasing solvent
      polarity in pure organic solvents. However, the free energies of association are
      weaker in the mixed aqueous solvent than in pure organic solvents. This indicates
      that dispersion and electrostatic interactions are relatively strong in the non
      aqueous environment. The results demonstrate that any successful model of
      antimalarial drug-Fe(III)PPIX interactions will need to take both solvation and
      electrostatic factors into account.

PMID- 14659644
TI  - Formation equilibria of nickel complexes with glycyl-histidyl-lysine and two
      synthetic analogues.
AB  - Complex-formation equilibria between the Ni(II) ion and the natural tripeptide
      glycyl-L-histidyl-L-lysine have been investigated. Two synthetic analogues, where
      the histidine residue has been substituted with L-4,5,6,7-tetrahydro-1H
      imidazo[4,5-c]pyridine-6-carboxylic acid (L-Spinacine) and L-1,2,3,4-tetrahydro
      isoquinolin-3-carboxylic acid (Tic), respectively, have been considered, as well.
      Different experimental techniques have been employed: potentiometry, calorimetry,
      visible spectrophotometry and CD spectroscopy. Structural hypotheses on the main
      complex species are suggested. Evidences on the formation of tetrameric species
      with the first ligand are shown. No involvement of the side-chain amino group of
      lysine residue in metal ion coordination was found.

PMID- 14659645
TI  - A formula for correlating pKa values determined in D2O and H2O.
AB  - A linear correlation between pH-meter readings in equivalent D2O and H2O
      solutions, determined experimentally, leads to a novel equation, which allows for
      a direct recalculation of pKa values measured in D2O into a H2O equivalent:
      pKH=0.929pKH*+0.42. The comparison of this equation with the previously used
      approach is discussed.

PMID- 14659646
TI  - Multinuclear NMR spectroscopy and antitumor activity of novel platinum(II)
      complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines.
AB  - Novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5
      a]pyrimidines have been synthesized and characterized by infrared and
      multinuclear magnetic resonance spectroscopic techniques (1H, 13C, 15N, 195Pt).
      The complexes are of two types: [PtCl2(L)2] and [PtCl2(NH3)(L)], where L=5,7
      diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) and 5,7-ditertbutyl-1,2,4
      triazolo[1,5-a]pyrimidine (dbtp). Significant 15N NMR upfield shifts (92-95 ppm)
      were observed for N(3) atom indicating this nitrogen atom as a coordination site.
      The molecular structure suggest that Pt(II) ion has the square planar geometry
      with N(3) bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines, N-bonded
      second ligand (NH3 for cis-[PtCl2(NH3)(L)] or, respectively, 5,7-disubstituted
      1,2,4-triazolo[1,5-a]pyrimidines for cis-[PtCl2L2]) and two cis chloride anions.
      The antiproliferative activity in vitro of complexes (1-4) have been tested
      against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non
      small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The
      results indicate a moderate antiproliferative activity of (4) against the cells
      of rectal, breast and bladder cancer and a marked and selective cytotoxic effect
      of (1-3) against the cells of all studied human cancer lines.

PMID- 14659647
TI  - Metal catalyzed oxidation of tyrosine residues by different oxidation systems of
      copper/hydrogen peroxide.
AB  - Metal-catalysed oxidation (MCO) reactions result in the formation of reactive
      oxygen species (ROS) in biological systems. These ROS cause oxidative stress that
      contributes to a number of pathological processes leading to a variety of
      diseases. Tyrosine is one residue that is very susceptible to oxidative
      modification and the formation of dityrosine (DT) and 3,4-dihydroxyphenylalanine
      (DOPA) have been widely reported in a number of diseases. However, the mechanisms
      of MCO of tyrosine in biological systems are poorly understood and require
      further investigation. In this study we investigated the mechanism of DT and DOPA
      formation by MCO using N-acetyl tyrosine ethyl ester as a model for tyrosine in
      proteins and peptides. The results showed that DT formation could be observed
      upon Cu2+/H2O2 oxidation at pH 7.4. Our results indicate that it is unlikely to
      be via Fenton chemistry since Cu+/H2O2 oxidative conditions did not lead to the
      formation of DT.

PMID- 14659648
TI  - Determination of the formal reduction potential of Lumbricus terrestris
      hemoglobin using thin layer spectroelectrochemistry.
AB  - The formal reduction potential (Eo') of Lumbricus terrestris hemoglobin was
      determined using thin layer spectroelectrochemistry as 0.073 (+/-0.005) V vs
      Ag/AgCl (0.281 V vs SHE, standard hydrogen electrode). Nernst plots of Lumbricus
      terrestris hemoglobin with tris-bipyridinecobalt(II) as a mediator titrant have
      similar linear slopes as Nernst plots of horse heart myoglobin with
      hexaamineruthenium(II) as a mediator titrant.

PMID- 14659650
TI  - Contemporary in vitro spectrum of activity summary for antimicrobial agents
      tested against 18569 strains non-fermentative Gram-negative bacilli isolated in
      the SENTRY Antimicrobial Surveillance Program (1997-2001).
AB  - The frequency of occurrence and antimicrobial susceptibility patterns of 18569
      non-fermentative Gram-negative bacilli consecutively collected as part of the
      SENTRY Antimicrobial Surveillance Program were summarized. The isolates were
      tested by the broth microdilution method in three coordinator laboratories using
      common reagents and reference methodologies. The most frequently isolated
      pathogen was Pseudomonas aeruginosa (11968 isolates; 64.5%) followed by
      Acinetobacter spp. (3468 isolates; 18.7%) and Stenotrophomonas maltophilia (1488
      isolates; 8.0%). The lowest resistance rates for P. aeruginosa documented were
      for amikacin (8%), meropenem (10%) and cefepime (10%), and all fluoroquinolones
      tested showed similar resistance rates (22-24%). The most active compounds
      against Acinetobacter spp. were the carbapenems, imipenem (11% resistance) and
      meropenem (12% resistance) followed by cefepime (31% resistance) and gatifloxacin
      (32% resistance). Very few compounds showed reasonable in vitro activity against
      S. maltophilia, with the most active antimicrobial agents being
      trimethoprim/sulphamethoxazole, gatifloxacin and levofloxacin (5-6% resistance).
      Resistance surveillance among these organisms remains necessary to guide
      empirical antimicrobial therapy, especially for these less frequently isolated
      and difficult to test pathogens.

PMID- 14659651
TI  - In vitro activities of nine peptide deformylase inhibitors and five comparator
      agents against respiratory and skin pathogens.
AB  - The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical
      evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin,
      erythromycin and telithromycin against a range of respiratory and skin pathogens
      (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae,
      Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus
      irrespective of beta-lactam or fluoroquinolone susceptibility. Against
      Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the
      most active compound. Overall these data suggest that PDF inhibitors are an
      interesting new class of antimicrobial worthy of further investigation in the
      treatment of respiratory tract and skin infections.

PMID- 14659652
TI  - Susceptibility of Mycobacterium ulcerans to a combination of amikacin/rifampicin.
AB  - The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were
      estimated in the treatment of mice experimentally infected by Mycobacterium
      ulcerans and the risk of relapse after the treatment was evaluated. After 7 weeks
      of treatment with RIF or with the combination of AMK/RIF and 8 weeks with AMK
      alone, no viable bacilli were found in the infected tissues and these remained
      uninfected during the following 6 months. Among the mice treated with AMK alone,
      three mice relapsed, but the minimal inhibitory concentration of AMK for these
      isolates remained unchanged. With RIF alone, two mice relapsed and the minimal
      inhibitory concentration of these isolated strains was higher. However, with all
      the mice treated with both RIF and AMK, no relapse was observed.

PMID- 14659653
TI  - Investigation of methicillin-resistant Staphylococcus aureus showing reduced
      vancomycin susceptibility isolated from a patient with infective endocarditis.
AB  - A patient with infective endocarditis (IE) caused by methicillin-resistant
      Staphylococcus aureus (MRSA) was treated with vancomycin (VAN). VAN was
      ineffective, although therapeutic drug monitoring (TDM) indicated that the
      recommended trough level was maintained. Five MRSA isolates obtained at various
      times were analyzed to determine the minimum inhibitory concentration (MIC) and
      were subjected to population analysis, simulation analysis pulsed-field gel
      electrophoresis (PFGE). MRSA susceptible to VAN was isolated before and during
      the early stage of treatment, while an MRSA strain showing reduced VAN MIC was
      isolated during treatment. Simulation analysis indicated that the viable
      bacterial count only decreased to 10(-3) to 10(-4) cells after 72 h of
      incubation. The five MRSA strains isolated at various times were identical by
      PFGE.

PMID- 14659654
TI  - Pharmacodynamics of piperacillin in severely ill patients evaluated by using a
      PK/PD model.
AB  - Penetration of antiinfective drugs into soft tissues is essential for
      antimicrobial killing at the target site, but is substantially lower in severely
      ill patients compared with healthy subjects. The present study was conducted to
      assess the antimicrobial effect of piperacillin in severely ill patients. Strains
      of Staphylococcus aureus and Pseudomonas aeruginosa were exposed in vitro to
      concentrations of piperacillin, simulating the pharmacokinetic profiles measured
      in soft tissue of patients and healthy subjects. The simulation for patients
      resulted in effective killing, whereas bacterial regrowth was detected for
      healthy subjects. Our in vitro simulation showed that bacterial killing may be
      effective in severely ill patients despite relatively low concentrations of
      piperacillin at the target site. This finding is due to impaired renal function
      and subsequently prolonged tissue and plasma half-lives of piperacillin in
      intensive care patients.

PMID- 14659655
TI  - Disposition and intracellular levels of moxifloxacin in human THP-1 monocytes in
      unstimulated and stimulated conditions.
AB  - Moxifloxacin uptake by human THP-1 monocytes was passive and initially linear and
      reached equilibrium after approximately 4 h. High intracellular concentrations
      were achieved and intracellular/extracellular [I/E] ratios were between 1925 and
      4575 for the lowest concentration of 0.004 microg/ml at pH 7.4 and 6.9. The
      uptake of moxifloxacin was reduced by sodium fluoride, -azide, -cyanide, low
      temperature and low pH. However, the uptake was not affected by any of the ion
      channel blockers. Adenosine demonstrated marginal competition with moxifloxacin
      for uptake suggesting a nucleoside transporter may be involved. The sodium-ATPase
      pump when blocked, also retarded moxifloxacin uptake at 2 and 4 h. This I/E ratio
      was high compared with other macrolides and indicateed that the monocyte may
      contain sufficient moxifloxacin levels to conduct the antibiotic throughout
      systemic circulation to infection sites. Efflux from THP-monocytes was
      essentially complete after 2 h indicating no long term sequestering of the
      antibiotic occurred. Disposition of the antibiotic within the THP-1 monocytes
      showed large amounts present in the nucleus and cytoplasm in stimulated and
      unstimulated cells. Increased amounts of the drug were found in the THP-1
      monocytes as well as the endoplasmic reticulum and the isolated phagosomes after
      stimulation by zymogen A, Staphylococcus aureus or Streptococcus pneumoniae.

PMID- 14659656
TI  - Bactericidal effect of cethromycin (ABT-773) in an immunocompetent murine
      pneumococcal pneumonia model.
AB  - The efficacy of cethromycin was assessed against isolates of Streptococcus
      pneumoniae in the presence of neutrophils. Comparison with data from our previous
      neutropenic model revealed that the presence of neutrophils enhanced the
      bacteriostatic and bactericidal effect of cethromycin by an average of two- to
      four-times, respectively.

PMID- 14659657
TI  - Efficacy of human salivary mucin MUC7-derived peptide and histatin 5 in a murine
      model of candidiasis.
AB  - MUC7 16-mer (residues 36-51 of human salivary mucin, MUC7) and histatin 5 possess
      potent in vitro antifungal activity. In the present study, we have evaluated the
      efficacy of these peptides in vivo using the experimental model of murine vulvo
      vaginal candidiasis. The treatment groups included MUC7 16-mer, histatin 5,
      clotrimazole (all in pluronic F127 gel), and placebo (gel alone). Mice were
      treated intravaginally for 7 consecutive days. At the end of the treatment,
      anticandidal activities were assessed by colony counts and by histological
      examination. All groups except clotrimazole presented positive cultures; no
      statistically significant differences were found in fungal burden amongst placebo
      and any treatment group except clotrimazole. Histopathological findings confirmed
      the microbiological results; all groups with the exception of clotrimazole showed
      variable signs of infection.

PMID- 14659658
TI  - The indirect pathogenicity of Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia has at least two inducible beta-lactamases, L1 and
      L2, which can hydrolyze almost all classes of beta-lactam antimicrobial agents.
      This study was done to verify the indirect pathogenicity of S. maltophilia that
      could promote the growth of other beta-lactam agent-susceptible bacteria in a
      mixed culture. We counted CFU of beta-lactam agent-susceptible bacteria under the
      presence of imipenem or ceftazidime in a pure culture and mixed culture with S.
      maltophilia. Our results showed that beta-lactamase leaking from S. maltophilia
      can encourage the growth of Serratia marcescens and Pseudomonas aeruginosa even
      if imipenem or ceftazidime was supplemented. This study discovered a blind spot
      in chemotherapy against an indirect pathogen such as S. maltophilia.

PMID- 14659659
TI  - Modification of mitogen-driven lymphoproliferation by ceftriaxone in normal and
      immunocompromised mice.
AB  - Cyclophosphamide-treated mice are proposed as a model to assay immunomodulation
      by antimicrobial agents in immunocompromised animals. Cyclophosphamide-treated
      BALB/c mice developed temporary leukopenia, myelopenia and spleen atrophy that
      was followed by splenomegaly. Cells from both atrophic and hypertrophic spleens
      exhibited impaired responses to mitogens and suppressed the mitogen-driven
      proliferation of normal splenocytes. This experimental model was applied to the
      study of immunomodulation by ceftriaxone. Ceftriaxone did not worsen the
      cyclophosphamide-damaged immunity mechanisms. On the contrary, cyclophosphamide
      induced suppression of lymphoproliferation in response to concanavalin A was
      attenuated by ceftriaxone.

PMID- 14659660
TI  - Activity of combinations of ceftazidime, imipenem and pefloxacin against
      Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.
AB  - The chequerboard technique was used to look for synergistic combinations of
      ceftazidime, imipenem and pefloxacin. The synergistic combinations were used in
      vivo in mice experimentally infected with Escherichia coli, Salmonella
      typhimurium and Pseudomonas aeruginosa. In vitro ceftazidime/imipenem,
      ceftazidime/pefloxacin and pefloxacin/imipenem combinations showed synergistic
      effects against Staphylococcus aureus and S. typhimurium and additive effects
      against P. aeruginosa. Only the ceftazidime/pefloxacin combination was
      synergistic against E. coli while the ceftazidime/imipenem and
      pefloxacin/imipenem combinations resulted in additive effects. In vivo,
      combination of ceftazidime/imipenem against E. coli infection and the
      pefloxacin/imipenem combination against S. typhimurium infection were protective.

PMID- 14659661
TI  - Audit of an antibiotic policy and microbiological investigations for treating
      bacteraemia in a large teaching hospital.
AB  - An audit of different approaches to guide empirical therapy in 78 cases of
      bacteraemia revealed poor utilisation of the antibiotic policy with resulting
      inadequate (P=0.005) or excessive (P<0.00001) antibiotic treatment and a trend to
      increased mortality. Eighty-seven percent of blood cultures were positive on Gram
      stain within 24 h but streamlined therapy was still judged excessive in 27%. The
      results show poor utilisation of an up-to-date antibiotic policy but confirm its
      potential benefits and the ability of traditional culture methods to guide
      antibiotic therapy in a useful time-scale.

PMID- 14659662
TI  - LightCycler gyrA mutation assay (GAMA) identifies heterogeneity in GyrA in
      Salmonella enterica serotypes Typhi and Paratyphi A with decreased susceptibility
      to ciprofloxacin.
AB  - Mutations in gyrA in strains of Salmonella enterica serotypes Typhi and Paratyphi
      A have been characterised by a LightCycler-based PCR-hybridisation gyrA mutation
      assay (GAMA) and by DNA sequencing. Four mutations (Ser-83 to Phe, Asp-87 to Asn,
      Ser-83 to Tyr and Asp-87 to Gly) have been identified in 13 strains of Typhi and
      three strains of Paratyphi A resistant to nalidixic acid (=nal(r)) and with
      decreased susceptibility to ciprofloxacin (=Cp(L)), with the mutation Ser-83 to
      Phe predominating. The results have demonstrated heterogeneity in gyrA in nal(r)
      Cp(L) strains of Typhi and Paratyphi A and may be useful for epidemiological
      investigations. No mutations in gyrA were identified in four Cp(L) strains of S.
      Typhi that were sensitive to nalidixic acid. The mechanism of decreased
      susceptibility to ciprofloxacin in these strains is under investigation.

PMID- 14659663
TI  - Prevalence and characterization of the mechanisms of macrolide, lincosamide and
      streptogramin resistance in viridans group streptococci.
AB  - The presence of erm genes conferring constitutive and inducible resistance, as
      well as that of the mefA gene conferring only constitutive resistance, was
      investigated using PCR in 70 erythromycin resistant (MIC>or=1 mg/l) strains of
      viridans group streptococci (VGS) (18 Streptococcus mitis biotype 1, 16 S. mitis
      biotype 2, 15 S. oralis, 12 S. salivarius and nine S. sanguis) isolated from the
      oropharynx of healthy Greek children. All of the 56 isolates belonging to
      resistance phenotype M harbored the mefA gene. All of the 14 isolates
      constitutively resistant to macrolides and lincosamides (phenotype CR) harbored
      the ermB gene. Co-presence of both genes was not observed, whereas class A erm
      gene (previously known as ermTR) was not detected. Our results are consistent
      with a possible role of VGS as a reservoir of resistance genes now prevalent in
      pathogenic species of streptococci.

PMID- 14659664
TI  - Avascular necrosis of the femoral head in a HIV-1 infected patient receiving
      lopinavir/ritonavir.
AB  - The wide use of protease inhibitors (PI) as part of a highly active
      antiretroviral (HAART) regimen is associated with the development of several side
      effects. Among these, the development of avascular necrosis (AVN) of the bone is
      being reported more frequently and it has been related both to the use of PI and
      to HIV-1 infection itself. We report here a case of AVN of the bone in a patient
      taking the new PI lopinavir (LPV)/ritonavir (RTV) as part of a HAART regimen.

PMID- 14659665
TI  - The occurrence and transferability of the resistance determinants in 50 amikacin
      resistant Enterococcus faecalis and Enterococcus faecium.

PMID- 14659666
TI  - A convenient synthesis of lepidimoide from okra mucilage and its growth-promoting
      activity in hypocotyls.
AB  - The total synthesis of the unsaturated disaccharide, lepidimoide 4-deoxy-beta-L
      threo-hex-4-enopyranuronosyl-(1-->2)-L-rhamnopyranose sodium salt, has been
      carried out from D-glucose and L-rhamnose (Tetrahedron Lett. 1993, 34, 2653), but
      the process is very long and complicated. A method for more easily producing this
      compound and in large quantities is necessary for further research. We have
      succeeded in conveniently synthesizing lepidimoide from okra (Hibiscus esculentus
      L.) fruit mucilage. At the same time, the isomer (epi-lepidimoide) was obtained
      as a byproduct. The structure was determined as the 4-deoxy-beta-L-threo-hex-4
      enopyranuronosyl-(1-->2)-6-deoxy-L-glucopyranose sodium salt by spectral
      analysis. We found that lepidimoide easily epimerized to epi-lepidimoide in
      alkaline media. Both lepidimoide and epi-lepidimoide exhibited the same high
      activity in the cockscomb hypocotyls elongation test.

PMID- 14659667
TI  - Synthesis of an apiose-containing disaccharide fragment of rhamnogalacturonan-II
      and some analogues.
AB  - Beta-rhamnosylation of methyl 2-C-hydroxymethyl-2,3-O-isopropylidene-beta-D
      erythrofuranoside and methyl 2,3-O-isopropylidene-beta-D-ribofuranoside was
      achieved using 4-O-acetyl-2,3-O-carbonyl-alpha-L-rhamnopyranosyl bromide and Ag2O
      as a promoter. Deprotected disaccharides beta-L-Rhap-(1-->3')-beta-D-Apif-OMe and
      beta-L-Rhap-(1-->3')-beta-D-Ribf-OMe were compared to their alpha-rhamnosyl
      isomers which were prepared using conventional Helferich glycosylation.

PMID- 14659668
TI  - Synthesis of two oligosaccharides, the GPI anchor glycans from S. cerevesiae and
      A. fumigatus.
AB  - Two oligosaccharides, alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-
      >6)-alpha-D-Manp-(1-->4)-alpha-D-GlcpNAc (I) and alpha-D-Manp-(1-->3)-alpha-D
      Manp-(1-->2)-alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->6)-alpha-D-Manp-(1-->4)-alpha
      D-GlcpNAc (II), the glycosylphosphatidylinositol (GPI) anchor glycans from S.
      cerevesiae and A. fumigatus were synthesized as their methyl glycosides in a
      regio- and stereoselective manner. The pentasaccharide I was obtained from 6-O
      selective glycosylation of methyl 2,3-di-O-benzoyl-alpha-D-mannopyranosyl-(1-->4)
      2-acetamido-3,6-di-O-benzoyl-2-deoxy-alpha-D-glucopyranoside (8) with 2-O-acetyl
      3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D
      mannopyranosyl trichloroacetimidate (9), followed by benzoylation, deacetylation,
      and mannosylation, and then by deprotection. The hexasaccharide (II) was obtained
      via condensation of allyl 3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1-->2)
      3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (17) with 2,3,4,6-tetra-O-benzoyl
      alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-alpha-D-mannopyranosyl
      trichloroacetimidate (16), followed by deallylation, trichloroacetimidation, and
      coupling with acceptor (8), and finally by deprotection.

PMID- 14659669
TI  - Electrochemical synthesis and X-ray crystal structures of beta-D-2-phenylselenyl
      1,3,4,6-tetra-O-acetylglucopyranose and alpha-D-2-phenylselenyl-1,3,4,6-tetra-O
      acetylmannopyranose.
AB  - Electrochemical acetoxyphenylselenation of 3,4-dihydro-2H-pyran and D-3,4,6-tri-O
      acetylglucal was studied. The constant current electrolysis (50mA) of
      dihydropyran and diphenyl diselenide in an acetic acid solution of
      tetramethylammonium chloride was performed at room temperature in an undivided
      cell using a graphite anode and an aluminum cathode and yielded trans-DL-2
      acetoxy-3-phenylselenyltetrahydropyran (27%), in agreement with Markovnikov's
      rule. The analysis of the 1H NMR spectral data showed that the acetoxy and
      phenylselenyl groups adopt axial positions in the most stable conformation of
      this compound due to the anomeric effect. Under the same conditions D-3,4,6-tri-O
      acetylglucal afforded D-2-phenylselenyl-1,3,4,6-tetra-O-acetylglucopyranose and D
      2-phenylselenyl-1,3,4,6-tetra-O-acetylmannopyranose, which were separated by
      column chromatography and isolated in 87% overall yield (isomer ratio 60:40). The
      structures of these compounds were established by spectral data. Single crystal X
      ray structure determinations of the diastereomers are reported.

PMID- 14659670
TI  - A concise synthesis of two isomeric pentasaccharides, the O repeat units from the
      lipopolysaccharides of P. syringae pv. porri NCPPB 3364T and NCPPB 3365.
AB  - A concise synthesis of two isomeric pentasaccharides, alpha-L-Rhap-(1-->2)-alpha
      L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-[beta-D-GlcpNAc-(1-->2)]-alpha-L-Rhap (A) and
      alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-[beta-D-GlcpNAc-(1-->2)]-alpha-L-Rhap
      (1-->3)-alpha-L-Rhap (B), the O repeats from the lipopolysaccharides of
      Pseudonomonas syringae pv. porri NCPPB 3364T and 3365 was achieved via assembly
      of the building blocks, allyl 3,4-di-O-benzoyl-alpha-L-rhamnopyranoside (1),
      2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (2), allyl 4-O
      benzoyl-3-O-chloroacetyl-alpha-L-rhamnopyranoside (6), 3,4,6-tri-O-acetyl-2-deoxy
      2-phthalimido-beta-D-glucopyranosyl trichloroacetimidate (7), and allyl 2,4-di-O
      benzoyl-alpha-L-rhamnopyranoside (10). Coupling of 1 with 2 followed by
      deallylation and trichloroacetimidate formation gave the disaccharide donor 5,
      while condensation of 6 with 7, followed by dechloroacetylation, offered the
      disaccharide acceptor 9. Then, 5 was coupled with 10 to obtain the trisaccharide
      11, and subsequent deallylation and trichloroacetimidate formation furnished the
      trisaccharide donor 13. Coupling of 9 with 13, followed by deprotection, afforded
      pentasaccharide 19, while condensation of 9 with 5, followed by deallylation and
      trichloroacetimidate formation, gave the tetrasaccharide donor 16, whose coupling
      with 10 and subsequent deprotection yielded another pentasaccharide 22.

PMID- 14659671
TI  - First derivatives of myo-inositol 1,4,6-trisphosphate modified at positions 2 and
      3: structural analogues of D-myo-inositol 1,4,5-trisphosphate.
AB  - Novel, structurally modified potential mimics of the second messenger D-myo
      inositol 1,4,5-trisphosphate, based on the biologically active regioisomer D-myo
      inositol 1,4,6-trisphosphate, were synthesised. DL-5-O-Benzyl-1,4,6-tri-O-p
      methoxybenzyl-myo-inositol was the key intermediate for the preparation of the
      following compounds: DL-3-deoxy-, DL-3-deoxy-2-O-methyl-, DL-3-O-(2-hydroxyethyl)
      , DL-3-O-(3-hydroxypropyl)- and DL-3-O-(4-hydroxybutyl)-myo-inositol 1,4,6
      trisphosphate. DL-1,4,6-Tri-O -allyl-5-O-benzyl-myo-inositol was used to prepare
      DL-2-O-methyl-myo-inositol 1,4,6-trisphosphate. Deoxy-compounds were prepared by
      reduction of the corresponding tosylated intermediate using Super Hydride. The
      hydroxyalkyl groups were introduced at the C-3 of myo-inositol using the
      corresponding benzyl protected hydroxy alkyl bromide via the cis-2,3-O
      dibutylstannylene acetal. Methylation and benzylation at C-2 was accomplished
      using methyl iodide and benzyl bromide, respectively, in the presence of sodium
      hydride. Deblocking of p-methoxybenzyl groups was accomplished with TFA in
      dichloromethane and the allyl groups were removed by isomerisation to the cis
      prop-1-enyl derivative, which was hydrolysed under acidic conditions to give the
      corresponding 1,4,6-triol. The 1,4,6-triols were phosphitylated with the P(III)
      reagent bis(benzyloxy)(diisopropylamino)phosphine in the presence of 1H-tetrazole
      then oxidised with 3-chloroperoxybenzoic acid followed by deblocking by
      hydrogenolysis to give DL-2-O-methyl-, DL-3-O-deoxy-, DL-3-O-deoxy-2-O-methyl-,
      DL-3-O-(2-hydroxyethyl)-, DL-3-O-(3-hydroxypropyl)- and DL-3-O-(4-hydroxybutyl)
      myo-inositol 1,4,6-trisphosphate, respectively.

PMID- 14659672
TI  - Synthesis and intramolecular reactions of Tyr-Gly and Tyr-Gly-Gly related 6-O
      glucopyranose esters.
AB  - 6-O-(L-Tyrosylglycyl)- and 6-O-(L-tyrosylglycylglycyl)-D-glucopyranose were
      synthesized by condensation of the pentachlorophenyl esters of the respective di-
      and tripeptide with fully unprotected D-glucose. The intramolecular reactivity of
      the sugar conjugates was studied in pyridine-acetic acid and in dry methanol, at
      various temperatures and for various incubation times. The composition of the
      incubation mixtures was monitored by a reversed-phase HPLC method that permits
      simultaneous analysis of the disappearance of the starting material and the
      appearance of rearrangement and degradation products. To determine the influence
      of esterification of the peptide carboxy group on its amino group reactivity,
      parallel experiments were done in which free peptides were, under identical
      reaction conditions, incubated with D-glucose (molar ratios 1:1 and 1:5).
      Depending on the starting compound, different types of Amadori products (cyclic
      and bicyclic form), methyl ester of peptides, and Tyr-Gly-diketopiperazine were
      obtained.

PMID- 14659673
TI  - Expression of glycosphingolipids in lymph nodes of mice lacking TNF receptor 1:
      biochemical and flow cytometry analysis.
AB  - The expression of gangliosides and neutral glycosphingolipids (GSLs) in the lymph
      nodes of mice lacking the gene for the tumour necrosis factor-alpha receptor p55
      (TNFR1) has been investigated. GSL expression in the tissues of mice homozygous
      (TNFR1-/-) or heterozygous (TNFR1+/-) for the gene deletion was analysed by flow
      cytometry and high-performance thin-layer chromatography (HPTLC) followed by
      immunostaining with specific antibodies. HPTLC immunostaining revealed that lymph
      nodes from TNFR1-/- mice had reduced expression of ganglioside GM1b and GalNAc
      GM1b, neolacto-series gangliosides, as well as the globo- (Gb3, Gb4 and Gb5) and
      ganglio-series (Gg3 and Gg4) neutral GSLs. Flow cytometry of freshly isolated
      lymph node cells showed no significant differences in GSL expression, except for
      the GalNAc-GM1b ganglioside, which was less abundant on T lymphocytes from TNFR1
      /- lymph nodes. In TNFR1-/- mice, GalNAc-GM1b+/CD4+ T cells were twofold less
      abundant (3.8% vs 7.6% in the control mice), whereas GalNAc-GM1b+/CD8+ T cells
      were fourfold less abundant (5.0% vs 20.2% in the control mice). This study
      provides in vivo evidence that TNF signalling via the TNFR1 is important for the
      activation of GM1b-type ganglioside biosynthetic pathway in CD8 T lymphocytes,
      suggesting its possible role in the effector T lymphocyte function.

PMID- 14659674
TI  - Use of 13C chemical shift surfaces in the study of carbohydrate conformation.
      Application to cyclomaltooligosaccharides (cyclodextrins) in the solid state and
      in solution.
AB  - The anomeric carbon chemical shifts of free cyclomaltohexaose, -heptaose, 
      octaose, -decaose, and -tetradecaose (alpha-, beta-, gamma-, epsilon-, and eta
      cyclodextrin, respectively), and of alpha-cyclodextrin inclusion complexes, both
      in the solid state and in solution, were computed using ab initio 13C chemical
      shift surfaces for the D-Glcp-alpha-(1-->4)-D-Glcp linkage as a function of the
      glycosidic bond <Phi,Psi> dihedral angles. Chemical shift calculations in the
      solid state used <Phi,Psi> angle pairs measured from cyclodextrin X-ray
      structures as input. For estimations in the liquid state two different approaches
      were employed to account for dynamic averaging. In one, the computed solid-state
      anomeric carbon chemical shifts for each cyclodextrin D-Glcp monomer were simply
      averaged to obtain an estimate of the 13C shifts in solution. In the other,
      chemical shifts for the anomeric carbons were determined by averaging back
      calculated 13C shift trajectories derived from a series of 5 ns molecular dynamic
      simulations for the oligosaccharides with explicit representation of water. Good
      agreement between calculated and experimental 13C shifts was found in all cases.
      Furthermore, our results show that the ab initio 13C chemical shift surfaces are
      sufficiently sensitive to reproduce the small variations observed for the
      anomeric 13C shifts of the different cyclodextrin D-Glcp units in the solid state
      with excellent accuracy. The use of chemical shift surfaces as tools in
      conformational studies of oligosaccharides is discussed.

PMID- 14659675
TI  - The extracellular polysaccharide of Porphyridium sp.: an NMR study of lithium
      resistant oligosaccharidic fragments.
AB  - This study deals with the chemical characterization of an extracellular
      polysaccharide produced by the unicellular red alga Porphyridium sp. The sugar
      moiety of this polymer is composed of three neutral monosaccharides (Xyl, Glc,
      and Gal) and one uronic acid (GlcA). Proteins represent 5.5% of the dry weight of
      the polymer. Uronic degradation of this exopolysaccharide with lithium in
      ethylenediamine yielded two different oligosaccharides. The absolute
      configuration of the constitutive monosaccharides was chemically determined and
      revealed the presence of D-Xyl, D-Glc, D-, and L-Gal. The following
      oligosaccharide structures were established by NMR spectroscopy: [carbohydrate
      structure: see text].

PMID- 14659676
TI  - The structure of a sulfated galactan from Porphyra haitanensis and its in vivo
      antioxidant activity.
AB  - The sulfated galactan fraction F1 isolated from the red seaweed, Porphyra
      haitanensis, showed typical porphyran structure. It has a linear backbone of
      alternating 3-linked beta-D-galactosyl units and 4-linked alpha-L-galactosyl 6
      sulfate and 3,6-anhydro-alpha-L-galactosyl units. The L-residues are mainly
      composed of alpha-L-galactosyl 6-sulfate units, and the 3,6-anhydrogalactosyl
      units are minor. Partial methylation occurred at the C-6 position of the D
      galactosyl units and at the C-2 position of the 3,6-anhydro-alpha-L-galactosyl
      units. Intraperitoneal administration of F1 significantly decreased the lipid
      peroxidation in aging mice. F1 treatment increased the total antioxidant capacity
      and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH
      Px) in aging mice. The results indicated that F1 had significant in vivo
      antioxidant activity.

PMID- 14659677
TI  - Ab initio conformational maps for disaccharides in gas phase and aqueous
      solution.
AB  - Ab initio conformational maps for beta-lactose in both the gas phase and in
      aqueous solution have been constructed at the HF/6-31G(d,p) level of calculation.
      The results of the gas-phase ab initio calculations allow us to conclude that a
      rigid conformational map is able to predict the regions of the minima in the
      potential energy surface of beta-lactose, in full agreement with those found in
      the relaxed conformational map. The solvation effects do not give rise to any new
      local minimum in the potential energy surface of beta-lactose, but just change
      the relative Boltzmann populations of the conformers found in the gas-phase
      calculations. The values obtained for heteronuclear spin coupling constant
      (3J(H,C)), using the seven most stable conformers in solution are in good
      agreement with the available experimental values. This is a good indication that
      ab initio rigid conformational maps can be reliably used to sort the most stable
      conformers of beta-lactose.

PMID- 14659678
TI  - Arabinan-cellulose composite in Opuntia ficus-indica prickly pear spines.
AB  - The ultrastructure of the spines decorating the cladodes of the cactus Opuntia
      ficus-indica was investigated by optical microscopy, scanning and transmission
      electron microscopy, wide angle X-ray, and solid state 13C NMR analyses. Each
      spine consisted of a compact parallel arrangement of slender cellulosic fibers
      (0.4 mm in length and 6-10 microm in diameter) with small lumens. The fibers were
      disencrusted by alkali and sodium chlorite bleaching, yielding a remarkable
      arabinan-cellulose (1:1) product. X-ray fiber diagrams of the spines before and
      after purification confirmed the presence of crystalline cellulose domains with
      molecular axis parallel to the spine axis. CP-MAS 13C T1 NMR data showed a strong
      interaction at a nanometric level of a fraction of the arabinan and the cellulose
      crystalline domains. By sequential hydrothermal extractions, followed by a
      trifluoroacetic acid treatment, a relatively pure cellulose was isolated while
      the extracted fibers became fibrillated into slender microfibrils having no more
      than 4-6 nm diameter. The hydrothermal extract yielded the alpha-L-arabinofuranan
      consisting of a chain of (1-->5)-linked L-arabinosyl residues with branching
      either at C-2 or C-3 or at both C-2 and C-3. Taken together, these observations
      suggest that the bulk of the spine fibers consists of an intimate composite of
      cellulose microfibrils embedded in an arabinan matrix.

PMID- 14659679
TI  - Kinetics and mechanism of the oxidation of D-fructose by vanadium(V) in H2SO4
      medium.
AB  - The oxidative degradation of D-fructose by vanadium(V) in the presence of
      H(2)SO(4) has an induction period followed by autoacceleration. The kinetics and
      mechanism of the induction period have been studied at constant ionic strength.
      The reaction was followed spectrophotometrically by measuring the changes in
      absorbance at 350 nm. Evidence of induced polymerization of acrylonitrile and of
      reduction of mercuric chloride indicates that a free-radical mechanism operates
      during the course of reaction. Vanadium(V) is only reduced to vanadium(IV). The
      reaction is first and fractional order in [V(V)] and [D-fructose], respectively;
      but dependence on [H+] is complex, that is, [equation: see text]. At constant
      [H2SO4], sodium hydrogensulfate accelerates the reaction. The effect of added
      sodium sulfate on the H2SO4 and HSO4-catalyzed reaction is also reported. The
      activation parameters Ea=118 kJ mol(-1), DeltaH#=116 kJ mol(-1), DeltaS#=-301 J
      K(-1) mol(-1), and DeltaG#=213 kJ mol(-1) are calculated and discussed. Reaction
      products are also examined, and it is concluded that oxidation of D-fructose by
      vanadium(V) involves consecutive one-electron abstraction steps.

PMID- 14659680
TI  - Oligosaccharide identification and mixture quantification using Raman
      spectroscopy and chemometric analysis.
AB  - This work demonstrates the feasibility of using Raman spectroscopy for the
      analysis of small quantities of chemically similar oligosaccharides and their
      mixtures. Raman spectra were obtained from 10-microL aliquots of 1 mM solutions
      of maltotetraose and/or stachyose after deposition onto an electrochemically
      roughened silver substrate (and the resulting spectral features are attributed to
      a combination of normal and surface-enhanced Raman scattering). These compounds
      were selected because they are representative of glycans derived from post
      translationally modified proteins which, like these compounds, often consist of
      isomers of equal mass and similar shape. Replicate spectral measurements were
      recorded and processed using a partial-least-squares (PLS) classification and
      quantification algorithms with a leave-one-batch-out (LOBO) training and testing
      procedure. Spectra derived from solutions of individual sugars were identified
      with 100% accuracy, and mixtures of the two sugars were quantified with an
      average error of 2.7% in the relative maltotetraose/stachyose composition for
      mixtures with a total oligosaccharide concentration of 1 mM.

PMID- 14659681
TI  - A convenient synthesis of GDP D-glycero-alpha-D-manno-heptopyranose.
AB  - GDP D-glycero-alpha-D-manno-Heptopyranose has been prepared in good overall yield
      from 2,3,4,6,7-penta-O-acetyl-D-glycero-D-manno-heptopyranose by a short-step
      synthesis. Phosphitylation using the phosphoramidite procedure afforded the alpha
      anomer in high selectivity. Subsequent oxidation and partial deprotection gave
      the acetylated phosphate derivative, which was subjected to the coupling reaction
      with GMP-morpholidate to furnish the acetylated heptose nucleoside diphosphate in
      good yield. De-O-acetylation and final purification afforded the target GDP D
      glycero-alpha-D-manno-heptopyranose, which serves as the substrate of the
      heptosyl transferase in Aneurinibacillus thermoaerophilus DSM 10155 and occurs as
      an intermediate in the biosynthesis of GDP 6-deoxy-heptose in Yersinia
      pseudotuberculosis.

PMID- 14659682
TI  - Facile preparation of the alpha-Gal-recognizing Griffonia simplicifolia I-B4
      isolectin.
AB  - The B4 isolectin from Griffonia simplicifolia is of great utility as a reagent
      for the identification of alpha-D-galactopyranosyl end groups. Its separation
      from isolectins containing A subunits has been greatly improved by a simple,
      rapid procedure using a column of N-acetylgalactosamine coupled to vinyl sulfone
      activated Sepharose 4B to selectively retain the A subunit-containing isolectins.
      The procedure has the advantages over previous affinity procedures of speed (the
      isolation of B4 isolectin can be achieved in one day), simplicity, and high
      degree of resolution of the B4 isolectin.

PMID- 14659683
TI  - Structure of the O-polysaccharide of Xanthomonas cassavae GSPB 2437.
AB  - The following structure of the O-polysaccharide of the phytopathogenic bacterium
      Xanthomonas cassavae GSPB 2437 was determined by sugar analysis along with 1H and
      13C NMR spectroscopy: [structure: see text].

PMID- 14659684
TI  - Low Mw sulfated curdlan with improved water solubility forms macromolecular
      complexes with polycytidylic acid.
AB  - The water solubility of curdlan was enhanced by partial sulfation at O-6.
      Circular dichroism measurements suggest that the sulfated curdlan with the degree
      of substitution (DS) from 0 to 8.7 mol% forms macromolecular complexes with
      polycytidylic acid (poly(C)). Although the thermal stability of the complexes
      decreased with increase in DS, this could be overlapped by addition of NaCl in
      the concentration above that of serum. The results clearly indicate that the
      drawback arising from the electrostatic repulsion between the anionic charges can
      be partially compensated by the presence of salt. Furthermore, the polynucleotide
      chain complexed with the sulfated curdlan was protected from the enzymatic
      hydrolysis, corroborating the assumption that the sulfated curdlan has an ability
      to bind poly(C).

PMID- 14659685
TI  - Error thresholds and the constraints to RNA virus evolution.
AB  - RNA viruses are often thought of as possessing almost limitless adaptability as a
      result of their extreme mutation rates. However, high mutation rates also put a
      cap on the size of the viral genome by establishing an error threshold, beyond
      which lethal numbers of deleterious mutations accumulate. Herein, I argue that a
      lack of genomic space means that RNA viruses will be subject to important
      evolutionary constraints because specific sequences are required to encode
      multiple and often conflicting functions. Empirical evidence for these
      constraints, and how they limit viral adaptability, is now beginning to
      accumulate. Documenting the constraints to RNA virus evolution has important
      implications for predicting the emergence of new viruses and for improving
      therapeutic procedures.

PMID- 14659686
TI  - Cell wall branches, penicillin resistance and the secrets of the MurM protein.
AB  - Production of low-affinity forms of penicillin-binding proteins (PBPs), although
      essential, is not sufficient to protect pneumococci against the inhibitory action
      of penicillin. Resistance also requires the newly identified protein MurM which,
      together with MurN, is involved with the synthesis of short peptide branches in
      the pneumococcal cell wall. Cells in which murM was inactivated produced cell
      walls without branches and also completely lost penicillin resistance. To
      understand these surprising observations a 3D-model of MurM was constructed,
      which helped to put into structural context several of the biochemical and
      genetic observations made about this protein.

PMID- 14659687
TI  - Sweet new world: glycoproteins in bacterial pathogens.
AB  - In eukaryotes, the combinatorial potential of carbohydrates is used for the
      modulation of protein function. However, despite the wealth of cell wall and
      surface-associated carbohydrates and glycoconjugates, the accepted dogma has been
      that prokaryotes are not able to glycosylate proteins. This has now changed and
      protein glycosylation in prokaryotes is an accepted fact. Intriguingly, in Gram
      negative bacteria most glycoproteins are associated with virulence factors of
      medically significant pathogens. Also, important steps in pathogenesis have been
      linked to the glycan substitution of surface proteins, indicating that the
      glycosylation of bacterial proteins might serve specific functions in infection
      and pathogenesis and interfere with inflammatory immune responses. Therefore, the
      carbohydrate modifications and glycosylation pathways of bacterial proteins will
      become new targets for therapeutic and prophylactic measures. Here we discuss
      recent findings on the structure, genetics and function of glycoproteins of
      medically important bacteria and potential applications of bacterial
      glycosylation systems for the generation of novel glycoconjugates.

PMID- 14659688
TI  - Translating tissue culture results into animal models: the case of Salmonella
      typhimurium.
AB  - Investigators use both in vitro and in vivo models to better understand
      infectious disease processes. Both models are extremely useful in research, but
      there exists a significant gap in complexity between the highly controlled
      reductionist in vitro systems and the largely undefined, but relevant variability
      encompassing in vivo animal models. In an effort to understand how Salmonella
      initiates disease at the intestinal epithelium, in vitro models have served a
      useful purpose in allowing investigators to identify molecular mechanisms
      responsible for Salmonella invasion of host cells and stimulation of host
      inflammatory responses. Identification of these molecular mechanisms has
      generated hypotheses that are now being tested using in vivo models. Translating
      the in vitro findings into the context of an animal model and subsequently to
      human disease remains a difficult challenge for any disease process.

PMID- 14659689
TI  - Hard labour: bacterial infection of the skeleton.
AB  - The skeleton is the largest mammalian organ system, containing a myriad of blood
      vessels, tissue surfaces and bone cells for bacterial colonization. Although rock
      like, the skeleton is a dynamic structure that is undergoing constant
      remodelling. This is the result of the opposing actions of two key cells: the
      osteoblast, which produces bone, and the osteoclast, a multinucleate cell that
      'eats' bone. It is not generally realized that the most prevalent chronic
      bacterial diseases of Homo sapiens afflict the skeleton. Several pathogens, and
      members of the normal microbiota, have evolved specific cellular and molecular
      mechanisms for invading bone, including its cellular constituents. The host
      cellular pathways that are activated and lead to destruction or loss of the bone
      matrix will be described.

PMID- 14659690
TI  - Subclinical prion infection.
AB  - Prion diseases are transmissible neurodegenerative disorders that include scrapie
      in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob
      disease (CJD) in humans. The principal component of the infectious agent
      responsible for these diseases appears to be an abnormal isoform of the host
      encoded prion protein (PrP), designated PrP(Sc). Prion diseases are transmissible
      to the same or different mammalian species by inoculation with, or dietary
      exposure to, infected tissues. Although scrapie in sheep has been recognized for
      over 200 years, it is the recent epidemic of BSE that has centred much public and
      scientific attention on these neurodegenerative diseases. The occurrence of
      variant CJD in humans and the experimental confirmation that it is caused by the
      same prion strain as BSE has highlighted the need for intensive study into the
      pathogenesis of these diseases and new diagnostic and therapeutic approaches. The
      existence and implications of subclinical forms of prion disease are discussed.

PMID- 14659691
TI  - Innate immunity: involvement of new neuropeptides.
AB  - Secretory granules of chromaffin cells from the adrenal medulla store
      catecholamines and a variety of peptides that are secreted in the extracellular
      medium during exocytosis. Among these fragments, several natural peptides
      displaying antimicrobial activities at the micromolar range have been isolated
      and characterized. We have shown that these peptides, derived from the natural
      processing of chromogranins (CGs), proenkephalin-A (PEA) and free ubiquitin (Ub),
      are released into the circulation and display antibacterial and antifungal
      activities. In this review we focus on three naturally secreted antimicrobial
      peptides corresponding to CGA1-76 (vasostatin-I), the bisphosphorylated form of
      PEA209-237 (enkelytin) and Ub. In addition, the antimicrobial properties of the
      synthetic active domains of vasostatin-I (CGA47-66 or chromofungin) and Ub (Ub65
      76 or ubifungin) are reported.

PMID- 14659692
TI  - SAM domains: uniform structure, diversity of function.
AB  - Sterile alpha motif (SAM) domains are known to exhibit diverse protein-protein
      interaction modes. They can form multiple self-association architectures and also
      bind to various non-SAM domain-containing proteins. Surprising new work adds a
      completely unanticipated function for some SAM domains - the ability to bind RNA.
      Such functional diversity within a homologous protein family presents a
      significant challenge for bioinformatic function assignment.

PMID- 14659693
TI  - Bacterial mimics of eukaryotic GTPase-activating proteins (GAPs).
AB  - Bacterial GTPase-activating proteins (GAPs) subvert their host's eukaryotic Rho
      GTPases to their own advantage. Studies of bacterial GAPs extend our
      understanding of the action of eukaryotic GAPs, provide new tools for studies of
      cytoskeletal dynamics and offer new targets for anti-bacterial drugs.

PMID- 14659694
TI  - A substrate for telomerase.
AB  - Recent data indicates that controlled in vivo synthesis of telomeric DNA is a
      'menage a trois', in which sister chromatid termini paired by telomere end
      binding protein constitute a core substrate for a telomerase dimer. Such an
      arrangement could serve to fine tune synthesis of telomeric DNA and might ensure
      similar telomerase processivity for paired sister chromatid termini, possibly to
      secure the maintenance of individual telomere lengths in daughter cells. It also
      suggests that the bona fide end-capping protein, which is likely to regulate
      telomerase by restricting access to chromosome termini, has escaped detection in
      man.

PMID- 14659695
TI  - The intracellular voyage of cholera toxin: going retro.
AB  - Cholera toxin (CT) and related AB(5)-subunit toxins move from the plasma membrane
      through the trans-Golgi and endoplasmic reticulum (ER) to the cytosol of host
      cells. The toxins exploit a specific glycolipid pathway rather than a protein
      pathway. They bind glycolipids that associate with lipid rafts at the cell
      surface, which carry the toxins retrograde to the Golgi and ER. In the ER, the A1
      chain of the CT unfolds and enters the cytosol by hijacking the cellular
      machinery that enables misfolded proteins to cross the membrane for degradation
      by the proteasome, a process termed retro-translocation. Upon entering the
      cytosol, the A1-chain rapidly refolds, avoids the proteasome and induces
      toxicity.

PMID- 14659696
TI  - NO-dependent protein nitration: a cell signaling event or an oxidative
      inflammatory response?
AB  - Tyrosine nitration is becoming increasingly recognized as a prevalent,
      functionally significant post-translational protein modification that serves as
      an indicator of nitric oxide (z.rad;NO)-mediated oxidative inflammatory
      reactions. Nitration of proteins modulates catalytic activity, cell signaling and
      cytoskeletal organization. Several reactions mediate protein nitration, and all
      predominantly depend on z.rad;NO- and nitrite-dependent formation of nitrogen
      dioxide, a species capable of nitrating aromatic amino acids, nucleotides and
      unsaturated fatty acids. Here, we review the mechanisms that mediate in vivo
      protein nitration and how nitration of specific tyrosine residues impacts on
      protein function.

PMID- 14659697
TI  - TPR proteins: the versatile helix.
AB  - Tetratrico peptide repeat (TPR) proteins have several interesting properties,
      including their folding characteristics, modular architecture and range of
      binding specificities. In the past five years, many 3D structures of TPR domains
      have been solved, revealing at a molecular level the versatility of this basic
      fold. Here, we discuss the structure of TPRs and highlight the diversity of
      arrangements and functions that are associated with these ubiquitous domains.
      Genomic analyses of the distribution of TPR domains are presented along with
      implications for protein engineering.

PMID- 14659698
TI  - Functional regulation of p73 and p63: development and cancer.
AB  - The transcription factor and tumour suppressor p53 and its two homologues p63 and
      p73 form a family of proteins. p63 and p73 show much greater molecular complexity
      than p53 because they are expressed both as multiple alternatively spliced C
      terminal isoforms, and as N-terminally deleted, dominant-negative proteins that
      show reciprocal functional regulation. In addition, several other factors, such
      as post-translational modifications and specific and common family regulatory
      proteins, result overall in subtle modulation of their biological effects.
      Although all p53, p63 and p73 family members are regulators of the cell cycle and
      apoptosis, the developmental abnormalities of p73- and p63-null mice do not show
      enhanced tumour susceptibility of p53 knockouts, suggesting that complex
      regulatory processes modulate the functional effects of this family of proteins.

PMID- 14659699
TI  - Altered function and regulation of cardiac ryanodine receptors in cardiac
      disease.
AB  - In cardiac muscle, the ryanodine receptor (RyR2) on the sarcoplasmic reticulum
      (SR) releases the calcium required for muscle contraction. The magnitude of
      Ca(2+) release by RyR2, which is subject to regulation by several physiological
      mediators, determines cardiac contractility. In heart failure, chronic
      stimulation of the beta-adrenergic signaling pathway leads to
      hyperphosphorylation of RyR2 by protein kinase A, which dissociates calstabin2
      (FKBP12.6) from the receptor. Calstabin2-depleted channels display altered
      channel gating and can cause diastolic Ca(2+) release from the SR. This release
      depletes the SR Ca(2+) stores, leading to reduced myocardial contractility.
      Mutant RyR2, found in patients with catecholaminergic polymorphic ventricular
      tachycardia, has decreased calstabin2 binding affinity, which can trigger
      ventricular arrhythmias and sudden cardiac death after stress and exercise. Thus,
      defects in RyR2 have been linked to heart failure and exercise-induced sudden
      cardiac death and might provide novel therapeutic targets for the treatment of
      these common diseases of the heart.

PMID- 14659700
TI  - Historical review: another 50th anniversary--new periodicities in coiled coils.
AB  - In 1953, Francis Crick and Linus Pauling both proposed models of supercoiled
      alpha helices ('coiled coils') for the structure of keratin. These were the first
      attempts at modelling the tertiary structure of a protein. Crick emphasized the
      packing mode of the side-chains ('knobs-into-holes'), which required a
      periodicity of seven residues over two helical turns (7/2) and a supercoil in the
      opposite sense of the constituent helices. By contrast, Pauling envisaged a
      broader set of periodicities (4/1, 7/2, 18/5, 15/4, 11/3) and supercoils of both
      senses. Crick's model became canonical and the 'heptad repeat' essentially
      synonymous with coiled coils, but 50 years later new crystal structures and
      protein sequences show that the less common periodicities envisaged by Pauling
      also occur in coiled coils, adding a variant packing mode ('knobs-to-knobs') to
      the standard model. Pauling's laboratory notebooks suggest that he searched
      unsuccessfully for this packing mode in 1953.

PMID- 14659701
TI  - Out of the Amazon: Theobroma cacao enters the genomic era.
AB  - Theobroma cacao has long been a crop of near-mystical human importance among
      indigenous Mesoamerican cultures and its importance in modern culture is growing
      with new realizations of the potential health benefits of cocoa polyphenolic
      compounds. However, cultivated T. cacao is vulnerable to emerging disease
      pressures because it has a narrow genetic base, and systematic genetic
      improvement of the crop is imperative. A wide range of genomic tools and
      resources has been developed and are providing the basis for genome-based
      breeding and gene discovery.

PMID- 14659702
TI  - Why are there so many carbohydrate-active enzyme-related genes in plants?
AB  - Plants contain far more carbohydrate-active enzyme-encoding genes than any other
      organism sequenced to date. The extremely large number of glycosidase and
      glycosyltransferase-related genes in plant genomes can be explained by the
      complex structure of the plant cell wall, by ancient genome duplication and by
      recent local duplications, but also by the recent emergence of novel and
      unrelated protein functions based on widely available pre-existing scaffolds.

PMID- 14659703
TI  - Unraveling the functions of glycosyltransferase family 47 in plants.
AB  - The function of glycosyltransferases (GTs) from family GT47 was first identified
      in animal exostosins as beta-glucuronyltransferase involved in the synthesis of
      heparan sulfate. Two recent papers report the functions of two plant members in
      this family as a pectin beta-glucuronyltransferase and a xyloglucan beta
      galactosyltransferase. These findings greatly extend our understanding of the
      biological functions of family GT47 and also represent an important leap toward
      the molecular dissection of cell wall biosynthesis.

PMID- 14659704
TI  - Growth of plant culture.
AB  - A series of articles by Nick Battey published throughout 2003 has been
      challenging plant scientists to embrace plant culture. Fine art, literature,
      mythology, plant lore, religion, philosophy and plant science all contribute to
      plant culture and Battey believes that it is up to us, the scientists, to
      stimulate greater appreciation of our work by striving for a richer culture.

PMID- 14659705
TI  - A molecular view of plant centromeres.
AB  - Although plants were the organisms of choice in several classical centromere
      studies, molecular and biochemical studies of plant centromeres have lagged
      behind those in model animal species. However, in the past several years, several
      centromeric repetitive DNA elements have been isolated in plant species and their
      roles in centromere function have been demonstrated. Most significantly, a
      Ty3/gypsy class of centromere-specific retrotransposons, the CR family, was
      discovered in the grass species. The CR elements are highly enriched in chromatin
      domains associated with CENH3, the centromere-specific histone H3 variant. CR
      elements as well as their flanking centromeric satellite DNA are actively
      transcribed in maize. These data suggest that the deposition of centromeric
      histones might be a transcription-coupled event.

PMID- 14659706
TI  - Lignins and lignocellulosics: a better control of synthesis for new and improved
      uses.
AB  - The composition and structure of lignified walls has a dramatic impact on the
      technological value of raw materials. The chemical flexibility of the secondary
      cell wall has been demonstrated and it is now possible to develop strategies to
      optimize its composition through genetic engineering. Thanks to functional
      genomics, new target genes of both plant and microbial origin are rapidly
      becoming available for this purpose and their use will open new avenues for
      producing tailor-made plant products with improved properties. Moreover, the
      major proportion of terrestrial plant biomass comprises lignified cell walls and
      this reservoir of carbon should be increasingly exploited for the production of
      chemicals and energy within the context of sustainable development. For example,
      the design of plants suitable for downstream conversion processes, such as the
      production of bioethanol, and the exploitation of microorganisms and microbial
      enzymes for biomass pretreatments or for the production of novel chemicals.

PMID- 14659707
TI  - Breaking down taxonomic barriers in polyploidy research.
AB  - Polyploidy is important in the evolutionary history of plants, and it has played
      a crucial role in shaping the genome structures of all eukaryotes. New and
      rapidly improving techniques in genomics, cytogenetics and molecular ecology have
      resulted in a dramatic increase in publications about duplicate genes, genome
      rearrangements and detection of ancient duplication events. Similarly, research
      associated with the origins of polyploidy, its persistence in natural populations
      and the resulting ecological consequences is receiving more attention. Although
      polyploidy research has been conducted using both animal and plant systems,
      inferences based on cross-disciplinary comparisons have been rare. Here, I review
      recent developments in the field in both plants and animals, emphasizing the
      benefits of communication between the two groups.

PMID- 14659708
TI  - Tracking genes from seed to supermarket: techniques and trends.
AB  - Analytical techniques to track plant genes in the environment and the food chain
      are essential for environmental risk assessment, government regulation and
      production and trade of genetically modified (GM) crops. Here, I review
      laboratory techniques to track plant genes during pre-commercialization research
      on gene flow and post-commercialization detection, identification and
      quantification of GM crops from seed to supermarket. At present, DNA- and protein
      based assays support both activities but the demand for fast, inexpensive,
      sensitive methods is increasing. Part of the demand has been generated by
      stringent food labeling and traceability regulations for GM crops. The increase
      in GM crops, changes in GM crop design, evolution of government regulations and
      adoption of risk-assessment frameworks will continue to drive development of
      analytical techniques.

PMID- 14659709
TI  - Gametophytic self-incompatibility inhibits pollen tube growth using different
      mechanisms.
AB  - Self-incompatibility (SI) is one of the most important mechanisms used by plants
      to prevent self-pollination and consequently inbreeding. It is genetically
      controlled by the S-locus, which allows the recognition and rejection of 'self'
      (S-phenotypically identical) pollen. Gametophytically controlled SI (GSI) is the
      most widespread SI system. To date, only two forms have been elucidated in detail
      at the molecular level, revealing two different stigmatic S-genes. Here we
      summarize the evidence for the use of two different mechanisms to inhibit
      incompatible pollen tube growth. Because the limited data suggest the independent
      evolution of these two GSI systems, it would be interesting to explore other GSI
      systems to determine the extent of the mechanistic diversity.

PMID- 14659710
TI  - Pollen recognition and rejection during the sporophytic self-incompatibility
      response: Brassica and beyond.
AB  - Many hermaphrodite flowering plants avoid self-fertilization through genetic
      systems of self-incompatibility (SI). SI allows a plant to recognize and to
      reject self or self-related pollen, thereby preserving its ovules for
      outcrossing. Genes situated at the S-locus encode the 'male' (pollen) and
      'female' (pistil) recognition determinants of SI. In sporophytic SI (SSI) the
      male determinant is expressed in the diploid anther, therefore haploid pollen
      grains behave with a diploid S phenotype. In Brassica, the male and the female
      determinants of SSI have been identified as a peptide ligand and its cognate
      receptor, respectively, and recent studies have identified downstream signalling
      molecules involved in pollen rejection. It now needs to be established whether
      the Brassica mechanism is universal in species with SSI, or unique to the
      Brassicaceae.

PMID- 14659712
TI  - What do patients expect from complete dentures?
AB  - OBJECTIVES: An investigation was undertaken with the aim of determining whether
      patients wearing complete dentures in dental hospital (DH) and dental practice
      (DP) had different expectations from their dentures, together with their
      requirements for information about denture construction and oral and denture
      care. METHODS: A total of 214 edentulous patients, with a mean age of 69 years,
      from DP (125) and DH (89) participated in the questionnaire-based study. A valid
      questionnaire (P-DEQ) was constructed which demonstrated good test-retest
      reliability (Cronbach's alpha 0.86). The P-DEQ sought to determine how patients
      responded to a series of questions related to what dentists are urged to achieve
      with complete dentures. The questions covered not only what might be termed
      "normative" expectations but also patients' perceived needs for further
      information about the stages of prosthodontic treatment and oral or denture care.
      RESULTS: Significant differences (p< or =0.001) emerged between the two groups;
      82% of the DH group thought it essential that their dentures caused no pain
      compared with 59% of the DP group; for "absence of slackness" (DH 87%; DP 65%),
      and "good bite" (DH 82%; DP 55%). No significant differences emerged for the
      other parameters investigated, but both groups had high expectations for ease of
      chewing, speech, and good appearance. Differences (p<0.05) between the groups
      also emerged with respect to the demand for more information regarding the stages
      involved in denture construction (DH 57%, DP 76%) and how to care for dentures
      (DH 75%, DP 89%). Large proportions of patients from both groups would prefer to
      have more information about the selection of teeth (71% DH, 72% DP), and how to
      care for their mouths (84% DH, 86% DP), but there were no differences between the
      groups in these parameters. CONCLUSIONS: Most patient expectations appear to
      equate with the normative view expressed in standard prosthodontic texts.
      However, expectations may differ not only between individuals but also between
      patient groups managed in teaching hospital and DP settings. Edentulous patients
      also need information regarding the stages involved in denture construction and
      how to care for their mouths and dentures. This may have implications for the
      management of edentulous patients in DP and dental hospital.

PMID- 14659713
TI  - Effect of heat treatments on machinability of gold alloy with age-hardenability
      at intraoral temperature.
AB  - OBJECTIVE: This study investigated the effect of heat treatment on the
      machinability of heat-treated cast gold alloy with age-hardenability at intraoral
      temperature using a handpiece engine with SiC wheels and an air-turbine handpiece
      with carbide burs and diamond points. METHODS: Cast gold alloy specimens
      underwent various heat treatments [As-cast (AC); Solution treatment (ST); High
      temperature aging (HA), Intraoral aging (IA)] before machinability testing. The
      machinability test was conducted at a constant machining force of 0.784N. The
      three circumferential speeds used for the handpiece engine were 500, 1,000 and
      1,500 m/min. The machinability index (M-index) was determined as the amount of
      metal removed by machining (volume loss, mm(3)). The results were analyzed by
      ANOVA and Scheffe's test. RESULTS: When an air-turbine handpiece was used, there
      was no difference in the M-index of the gold alloy among the heat treatments. The
      air-turbine carbide burs showed significantly (p<0.05) higher M-indexes than the
      diamond points after any heat treatments. With the SiC wheels, increasing the
      circumferential speed increased the M-index values for each heat treatment. The
      specimens heat-treated with AC, HA and IA had similar M-indexes at the lower
      speeds (500 and 1,000 m/min). The ST specimens exhibited the lowest M-index at
      the lower speeds. However, at the highest speed (1,500 m/min), there were no
      significant differences in the M-indexes among the heat treatments except for HA,
      which showed the highest M-index. CONCLUSION: There was no effect of heat
      treatment on the machinability of the gold alloy using the air-turbine handpiece.
      The heat treatments had a small effect on the M-index of the gold alloy machined
      with a SiC wheel for a handpiece engine.

PMID- 14659714
TI  - Use of the basic periodontal examination and radiographs in the assessment of
      periodontal diseases in general dental practice.
AB  - OBJECTIVES: The aims of this study were to investigate (1) the use of the basic
      periodontal examination (BPE) by general dental practitioners (GDPs) and their
      selection of radiographs for the assessment of periodontal disease and (2)
      whether this selection concurred with existing selection (referral) criteria.
      METHODS: Three mailings of a self-completion questionnaire were sent to 800 GDPs
      working in the National Health General Dental Service in England and Wales.
      Dentists were presented with six clinical scenarios for which they were asked to
      describe their use of radiographs. RESULTS: Ninety-one percent of dentists
      reported that they used the BPE in new patients, with 56% using it for all
      patients; 84% of dentists used BPE in recall patients. BPE use was related to the
      dentists' age and postgraduate qualifications. There was a wide variation in the
      radiographic views used for periodontal disease assessment. The choice of
      radiographs was not generally in line with the Faculty of General Dental
      Practitioners (UK) 1998 selection criteria, particularly for the clinical
      scenarios of pocketing >5 mm, irregular pocketing or pockets associated with
      teeth with heavy restorations. Sixty seven percent of dentists concurred with
      recommendations for radiographs for a suspected periodontal-endodontic lesion.
      CONCLUSIONS: A majority of dentists reported clinical screening for periodontal
      diseases using the BPE. There was considerable variation in the selection and use
      of radiographs and practice was not in line with existing guidelines for many
      clinical situations. Evidence-based referral criteria should be actively promoted
      to ensure high standards of radiographic practice in general dental practice.

PMID- 14659715
TI  - A clinical and radiographic evaluation of stainless steel crowns for primary
      molars.
AB  - AIM: This study was performed to evaluate clinically and radiographically the
      effect of stainless steel crowns placed on primary molars on gingival and bone
      structures. SAMPLE: 254 crowns were evaluated in a sample of 177 children aged
      3.5-12 years old with a mean age of 7 years. METHOD: The clinical parameters that
      were evaluated were, crown marginal extension, crown marginal adaptation, intact
      proximal contact, gingival index and the duration of presence of the crowns,
      together with the oral hygiene index of the child. Bitewing radiographs were
      viewed for extension and adaptation of crown margins and for evaluating the
      interproximal bone level. RESULTS: The results of the study showed that
      interproximal bone resorption was not significantly affected by either crown
      marginal extension or adaptation, preserving tight proximal contact between
      molars, oral hygiene level or duration of presence of the crown. On the other
      hand, there was significant bone resorption when the crown was judged
      radiographically as non-satisfactory. While oral hygiene level had a significant
      effect on the gingival index, presence or absence of proper proximal contact did
      not have an effect on the gingival index. CONCLUSION: It was concluded from this
      study that stainless steel crowns are still a valuable procedure that has no
      harmful effect on the gingiva and bone provided that good oral hygiene level was
      maintained.

PMID- 14659716
TI  - Thermal effects of the Er:YAG laser on a simulated dental pulp: a quantitative
      evaluation of the effects of a water spray.
AB  - OBJECTIVES: To quantify the temperature increments in a simulated dental pulp
      following irradiation with an Er:YAG laser, and to compare those increments when
      the laser is applied with and without water spray. METHODS: Two cavities were
      prepared on either the buccal or lingual aspect of sound extracted teeth using
      the laser. One cavity was prepared with water spray, the other without and the
      order of preparation randomised. Identical preparation parameters were used for
      both cavities. Temperature increments were measured in the pulp chamber using a
      calibrated thermocouple and a novel pulp simulant. RESULTS: Maximum increments
      were 4.0 degrees C (water) and 24.7 degrees C (no water). Water was shown to be
      highly significant in reducing the overall temperature increments in all cases
      (p<0.001; paired t-test). None of the samples prepared up to a maximum of 135 J
      cumulative energy prepared with water spray exceeded that threshold at which
      pulpal damage can be considered to occur. Only 25% of those prepared without
      water spray remained below this threshold. DISCUSSION: Extrapolation of the
      figures suggests probably tolerable limits of continuous laser irradiation with
      water in excess to 160 J. With the incorporation of small breaks in the
      continuity of laser irradiation that occur in the in vivo situation, the
      cumulative energy dose tolerated by the pulp should far exceed these figures.
      CONCLUSIONS: The Er:YAG laser must be used in conjunction with water during
      cavity preparation. As such it should be considered as an effective tool for
      clinical use based on predicted pulpal responses to thermal stimuli.

PMID- 14659717
TI  - Effect of Er:YAG laser and organic matrix on porosity changes in human enamel.
AB  - OBJECTIVES: Cariostatic effects of lasers have been well documented in the past
      few decades; however, the mechanisms remain unclear. Our previous study revealed
      the statistically significant effect of organic matrix (OM) in the laser-induced
      caries prevention. The aim of the present study is to further investigate the
      role of organic matters in the laser-induced porosity changes. METHODS: Enamel
      powder from five sound molars was randomly divided into two samples. One sample
      was treated with approximately 10% NaClO solution to remove OM and the other was
      left untreated. Both groups were then subjected to irradiation by an Er:YAG
      laser. The samples were characterized by thermogravimetric analysis (TGA) and
      N(2) physico-adsorption. RESULTS: TGA results confirmed that the NaClO treatment
      had at least partially removed the OM in enamel powder. The surface area and pore
      volume of normal enamel powder decreased significantly after laser treatment. In
      contrast, in the NaClO-treated enamel powder, laser treatment did not
      significantly decrease the surface area and the pore volume remained almost
      unchanged. The substantial difference between the normal enamel powder and the
      NaClO-treated enamel powder after laser treatment confirmed the laser-induced
      blocking of OM in the micro-diffusion pathway in enamel. CONCLUSION: The findings
      in this study seemed to substantiate the "organic blocking theory" as one of the
      mechanisms in the laser-induced caries prevention.

PMID- 14659718
TI  - Oral health knowledge, attitude and behaviour among Saudi school students in
      Jeddah city.
AB  - OBJECTIVES: To assess the knowledge, attitude and behaviour in relation to
      periodontal health status among Saudi intermediate and high school students
      living in Jeddah, Kingdom of Saudi Arabia. METHODS: A dental health questionnaire
      was distributed to a random sample of a total of 2586 Saudi students from
      intermediate and high school, aged 12-18 years residing in Jeddah. RESULTS: While
      about 87.1% knew that tooth brush helps prevent periodontal disease, only 33.1%
      knew that using dental floss helps in preventing periodontal disease. Females
      used brushing and flossing more than males, while males used miswak more than
      females. Tooth brushing (P<0.001) and dental floss (P<0.015) were used more
      frequently among private subjects, while miswak was utilized more frequently
      among governmental school students (P<0.005). Dental pain was found to be the
      main reason for visiting the dentist among the target group. CONCLUSIONS: It
      appears that knowledge, attitude, and behaviour concerning periodontal health
      among young Saudi school students living in Jeddah city are in need of
      improvement.

PMID- 14659719
TI  - Adhesive permeability affects coupling of resin cements that utilise self-etching
      primers to dentine.
AB  - OBJECTIVES: To examine the effects of an experimental bonding technique that
      reduces the permeability of the adhesive layer on the coupling of resin cements
      to dentine. METHODS: Extracted human third molars had their mid to deep dentin
      surface exposed flat by transversally sectioning the crowns. Resin composite
      overlays were constructed and cemented to the surfaces using either Panavia F
      (Kuraray) or Bistite II DC (Tokuyama) resin cements mediated by their respective
      one-step or two-step self-etch adhesives. Experimental groups were prepared in
      the same way, except that the additional layer of a low-viscosity bonding resin
      (LVBR, Scotchbond Multi-Purpose Plus, 3M ESPE) was placed on the bonded dentine
      surface before luting the overlays with the respective resin cements. The bonded
      assemblies were stored for 24 h in water at 37 degrees C and subsequently
      prepared for microtensile bond strength testing. Beams of approximately 0.8 mm(2)
      were tested in tension at 0.5 mm/min in a universal tester. Fractured surfaces
      were examined under scanning electron microscopy (SEM). Additional specimens were
      prepared and examined with TEM using a silver nitrate-staining technique.
      RESULTS: Two-way ANOVA showed significant interactions between materials and
      bonding protocols (p<0.05). When bonded according to manufacturer's directions,
      Panavia F produced bond strengths that were significantly lower than Bistite II
      DC (p<0.05). The placement of an additional layer of a LVBR improved
      significantly the bond strengths of Panavia F (p<0.05), but not of Bistite II DC
      (p>0.05). SEM observation of the fractured surfaces in Panavia F showed rosette
      like features that were exclusive for specimens bonded according to
      manufacturer's directions. Such features corresponded well with the
      ultrastructure of the interfaces that showed more nanoleakage associated with the
      more permeable adhesive interface. The application of the additional layer of the
      LVBR reduced the amount of silver impregnation for both adhesives suggesting that
      reduced permeability of the adhesives resulted in improved coupling of the resin
      cements to dentin. CONCLUSIONS: Placement of an intermediate layer of a LVBR
      between the bonded dentine surface and the resin cements resulted in improved
      coupling of Panavia F to dentine.

PMID- 14659720
TI  - The influence of alumina abrasion and cement lute on the strength of a porcelain
      laminate veneering material.
AB  - OBJECTIVES: The purpose of the current study was to examine whether alumina
      abrasion regime influenced the necessary surface roughness conducive to
      mechanical interlocking prior to composite resin bonding. The impact of alumina
      abrasion and cement lute on the bi-axial flexure strength and associated Weibull
      Moduli (m) on the cemented surfaces of disc specimens of porcelain laminate
      veneer (PLV) materials was therefore investigated. METHODS: Sets of 20 Vitadur
      alpha dentine porcelain discs (15 mm diameter, 1.7 mm thickness) were condensed
      and prepared by abrading with 25, 50 or 110 microm alumina. Further specimen
      groups were stored wet or coated with a resin cement. Mean fracture strengths,
      standard deviations and associated m were determined using a ball-on-ring
      assembly. The surface roughness was assessed using profilometry and scanning
      electron microscopy. RESULTS: The one-way ANOVA revealed a significant reduction
      (P<0.05) between the means of the dry control and alumina abraded specimens. A
      significant increase in m was identified for 50 and 110 microm alumina abraded
      cemented specimens (6.1+/-1.4 and 6.0+/-1.3, respectively) compared with the 25
      microm alumina abraded cemented and non-alumina abraded cemented controls (3.9+/
      0.9 and 3.5+/-0.8, respectively). Increasing the alumina particle size utilised
      for the abrasion resulted in a decrease in the surface roughness (R(a) value)
      which is the arithmetic mean of the absolute departures of the roughness profile
      from the mean line. SIGNIFICANCE: Alumina abrasion acted to replace surface
      defects with a narrower distribution of defects. Composite resin polymerisation
      shrinkage may prevent surface flaws from being extended by healing the key
      surface defects and would appear to suggest that the use of a resin-based luting
      material may reduce the potential for crack propagation. Given the arrangement of
      ions across crack tips it is more likely that the resin composite cement enhanced
      strength by acting to heal key defects rather than imposing a compressive stress
      on the porcelain surface as suggested previously.

PMID- 14659721
TI  - Microleakage and SEM evaluation of fissure sealants placed by use of self-etching
      priming agents.
AB  - OBJECTIVES: This study evaluated the microleakage and internal seal of fissure
      sealants placed by use of self-etching priming agents in comparison to phosphoric
      acid etching of enamel. METHODS: Seventy-two caries-free extracted human molars
      were divided into six groups with 12 teeth each. Occlusal surfaces were cleansed
      by either pumicing (Groups I, III, V) or by 15-s air-abrasion treatment with 25
      microm aluminum oxide particles (Groups II, IV, VI). Fissures were sealed with
      the self-etching priming systems, Clearfil Liner Bond 2 (Groups I, II) or
      Resulcin AquaPrime (Groups III, IV). In Groups V and VI, sealants were placed
      after phosphoric acid etching. Half of the teeth in each group were thermocycled.
      After staining with 0.5% methylene blue, the teeth were sectioned for evaluation
      of microleakage. Internal adaptation of the fissure sealants was analyzed by SEM
      on replicas of cross sections. RESULTS: Independent of the methods used for
      cleansing of the occlusal surfaces, fissure sealants in Groups I and II showed
      significantly more microleakage and less sufficient internal seal as compared to
      sealants placed in Groups III to VI. Sealants placed by Resulcin AquaPrime
      (Groups III, IV) leaked significantly more than sealants applied after phosphoric
      acid etching (Groups V, VI) of the enamel. However, statistical analysis (H-test)
      did not reveal significant differences concerning the internal adaptation of
      sealants placed in Groups III, IV, V and VI. CONCLUSIONS: Concerning the
      microleakage data, use of the self-etching bonding systems, Clearfil Liner Bond 2
      and Resulcin AquaPrime, cannot be recommended for fissure sealing, since the
      sealing ability is less effective as compared to the conventional acid-etching
      technique.

PMID- 14659722
TI  - The reproducibility of ultrasonic enamel thickness measurements: an in vitro
      study.
AB  - OBJECTIVES: The diagnosis of tooth wear is mostly based on visual scoring
      systems. Recently, methods measuring ultrasonic enamel thickness have been
      proposed. The aim of this study was to evaluate the reproducibility and evaluate
      factors affecting variation of ultrasonic enamel thickness measurements in an in
      vitro set up. METHODS: Four observers (1-4) in two institutes (G and S) performed
      ultrasonic enamel thickness measurements at buccal and palatal surfaces of
      extracted teeth placed in a phantom jaw. A Panametrics 25DL thickness gauge
      (Panametrics, Waltham MA, USA), with a 15 MHz transducer, covered by a plexi
      glass delay line with a tip diameter of 2 mm was used, coupled to a laptop
      computer. After one week these measurements were repeated. Subsequently four
      selected teeth were measured 20 times at a fixed buccal site by one observer.
      Finally, two observers made ink marks with the instrument probe tip on the buccal
      and palatal surfaces of all teeth. This was repeated after one week. Digital
      images were made of the marked teeth and analysed to determine variation in
      positioning. The underlying enamel thickness variation was subsequently
      estimated. Results were analysed by calculating the 95% range of measurement
      variation (RMV, 4 x standard deviation) for each experiment. RESULTS: The main
      reproducibility experiment showed a 95% RMV of 0.79 mm (observer 1G), 0.64 mm
      (observer 2G), 0.63 mm (observer 3S), 0.71 mm (observer 4S), 0.51 mm (observer
      1S). The repeatability experiment showed a mean 95% RMV of 0.26 mm. The probe
      position variation in the cervical-incisal direction resulted in an estimated
      thickness 95% RMV of 0.10 mm (1G) and 0.09 mm (2G). CONCLUSIONS: It was concluded
      that, due to measurement variation, thickness changes of less than 0.33 mm cannot
      be detected reliably. Probe positioning and a poor repeatability were responsible
      for only a small part of the total variation. Hence other factors influencing
      variation in enamel thickness are still to be identified.

PMID- 14659724
TI  - Molecular differentiation of Mycobacterium bovis isolates. Review of main
      techniques and applications.
AB  - Until recently, none of the Mycobacterium bovis typing techniques permitted a
      satisfactory differentiation of isolates. During the last 10 years, the genome of
      pathogenic mycobacteria has been extensively studied, and phylogenetic analyses
      have shown that all (except Mycobacterium avium) belong to a single genetic
      species: the Mycobacterium tuberculosis complex. This increase in knowledge about
      the genome of these bacteria has lead to the discovery of molecular markers that
      allow us to differentiate isolates. Because of the phylogenetic proximity of the
      strains, even if most of these markers have been discovered in M. tuberculosis,
      they could be successfully adapted to the other bacteria of the M. tuberculosis
      complex, especially M. bovis. The most common markers in use today are the IS6110
      insertion sequence, the direct repeat (DR) region, the poly(GC) rich (PGRS)
      sequences and the variable number tandem repeats (VNTR) sequences. The
      corresponding typing techniques are briefly described, and current knowledge of
      polymorphism and marker stability is detailed. If molecular markers are to offer
      wide perspectives for field studies, these two characteristics (polymorphism and
      stability) must be taken into account when choosing the marker(s) used in a
      study. In this context, examples of the application of molecular typing
      techniques for M. bovis are reviewed, on the one hand with epidemiological
      studies for which the major problem is the comparison between isolates and, on
      the other, with more general studies about the population genetics of M. bovis in
      a given country, and about its history and its phylogeny.

PMID- 14659725
TI  - A field study on the effect of the dietary use of a clinoptilolite-rich tuff,
      alone or in combination with certain antimicrobials, on the health status and
      performance of weaned, growing and finishing pigs.
AB  - This study was conducted to assess the effect of dietary use of a clinoptilolite
      rich tuff (Cp) on health status and performance of weaned, growing and finishing
      pigs and its compatibility during simultaneous oral administration of
      antimicrobials (AM) such as enrofloxacin (E) or salinomycin (S). Weaners (720)
      were assigned in 2 experimental groups and 4 subgroups based on the inclusion or
      not of Cp and AM in their feed (subgroups: NC, ES, Cp, Cp+ES) in order to
      evaluate their health status, under PWDS prevailing herd conditions. A second
      part of the trial aimed to the evaluation of piglet performance under conditions
      with minimized PWDS herd risks. For this purpose, a second set of 264 weaners
      were assigned in 2 groups and 4 subgroups, in a respective manner. All piglets
      remained on-trial until slaughtering age; Cp was incorporated in their feed at a
      rate of 2% from the day of weaning until slaughtering. The health status
      evaluation consisted in monitoring piglets for adverse effects related to Cp
      consumption, average daily diarrhoea scoring during weaning and mortality rate
      calculations throughout. Performance evaluation included individual weighing at
      the end of weaning, growing and fattening periods and feed consumption
      assessments. Average daily gain (ADG), average daily feed intake (ADFI) and feed
      conversion ration (FCR) on a pen basis were further calculated. Cp ingestion was
      well tolerated by the piglets. Simultaneous administration of Cp and AM in feed,
      resulted in less severe forms of PWDS, which had a shorter clinical course
      (P<0.05). Mortality decreased (P<0.05) during the weaning period due to AM
      administration. Concerning mean pig body weight at the end of each production
      phase, both Cp and AM had favorable effects (P<0.05). ADG estimated for the whole
      observation period was improved (P<0.05) by Cp-use along with AM. FCR
      improvements (P<0.05) were noticed during the different stages of growth due to
      AM or Cp administration, while Cp/AM interaction was noticed only at weaning
      (P<0.05).

PMID- 14659726
TI  - Platelets enhance endotoxin-induced monocyte tissue factor (TF) activity in the
      horse.
AB  - Endotoxaemia is the leading cause of death in horses. Disseminated intravascular
      coagulation (DIG), stimulated by induced monocyte proteins, is a prominent
      feature. Monocyte-platelet cellular interactions are central to the vascular
      dysfunction produced by circulating endotoxin and are implicated in many
      thrombotic diseases in the horse. This study reports that endotoxin (0.01-10
      microg ml(-1)) and blood platelets (2.5 x 10(7) - 1 x 10(8) ml(-1)) are potent
      inducers of expression and activity of monocyte tissue factor (TF), the primary
      activator of the blood coagulation protease cascade. The co-incubation of
      endotoxin-stimulated monocytes with platelets resulted in greater production of
      this protein. Cycloheximide (1 mM) inhibited part of the stimulatory effect of
      endotoxin and/or platelets, the uninhibited part indicating de-encryption of cell
      surface TF. Hence, platelets are considered to be an important component of the
      endotoxin-stimulated response of equine monocytes. The role of platelets as
      potent stimulators of endotoxin-stimulated monocyte proteins and mediators in
      vitro is likely to be of significance in vivo in the clinical manifestations and
      management of endotoxaemia in the horse.

PMID- 14659727
TI  - The effect of region of application on absorption of ethanol and hexanol through
      canine skin.
AB  - The effect of region of application on the percutaneous penetration of solutes
      with differing lipophilicity was investigated in canine skin. Skin from the
      thorax, neck, back, groin, and axilla regions was harvested from Greyhound dogs
      and placed in Franz-type diffusion cells. Radiolabelled (14C) ethanol (Log P
      0.19) or hexanol (Log P 1.94) was applied to each skin section for a total of 5h.
      The permeability coefficient (kP, cm h(-1)) and residue of alcohol remaining in
      the skin were significantly (P=0.001) higher for hexanol compared to ethanol. In
      contrast, ethanol had a far greater maximum flux (Jmax, mol (cm2)(-1) h(-1)) than
      hexanol (P=0.001). A comparison of regional differences shows the kP and Jmax for
      ethanol in the groin was significantly lower (P=0.035) than the back. The kP and
      Jmax for hexanol were significantly higher (P=0.001) in the axilla than the other
      four skin sites. An understanding of factors influencing percutaneous drug
      movement is important when formulating topical preparations for the dog.

PMID- 14659728
TI  - Comparison of in vitro activities of biotransformation enzymes in pig, cattle,
      goat and sheep.
AB  - In vitro activities of cytochromes P450 (7-alkyl/aryloxyresorufin
      dealkyl(aryl)ases, testosterone hydroxylase/oxidase, 6-chlorzoxazone hydroxylase,
      7-methoxy-4-trifluoromethyl-coumarin demethylase, and lauric acid hydroxylases),
      reductases of carbonyl group (toward metyrapone, daunorubicin, glyceraldehyde,
      and 4-pyridine-carboxaldehyde) and conjugation enzymes (p-nitrophenol-UDP
      glucuronosyl transferase, 1-chloro-2,4-dinitrobenzene glutathione-S-tranferase)
      in young adults, males, non-castrated (N=6) farm animals were studied and
      compared. Presence of proteins cross-reacting with anti-human CYP3A4, CYP2C9, and
      CYP2E1 IgG was detected in all farm species. Bovine microsomes differed from
      other microsomes of farm species in very high 7-ethoxyresorufin-O-deethylase
      activity (CYP1A1/2). Significantly higher 7-methoxy-4-trifluoromethyl-coumarin
      demethylase (2-3 times) and 12-lauric acid hydroxylases (4-10 times) activities
      (probably corresponding to CYP2C and CYP4A, respectively) were found in ovine
      microsomes. The highest 6beta-testosterone hydroxylase activity, which is usually
      considered to be a CYP3A activity marker, was found in pig. Reductases of all
      farm animals display considerable ability to reduce carbonyl group of
      xenobiotics. Significant differences in level and activity of many
      biotransformation enzymes tested suggest that extrapolation of pharmacokinetic
      data obtained in one species to another (even related) could be misleading.

PMID- 14659729
TI  - Markers of bone metabolism in dog breeds of different size.
AB  - Serum and urinary markers of bone turnover may be of value in animals as
      noninvasive tools for determining the response of the skeleton to disease and
      injury. Although normal values for bone markers have been reported for the
      Beagle, concerns remain that breed to breed differences will complicate the
      interpretation of bone marker data in dogs. To explore this, we examined serum
      bone markers in two breeds of vastly different size, Pomeranians and Irish
      Wolfhounds. Our hypothesis was that serum concentrations of bone markers are
      similar in toy and giant dog breeds and fall within the same range as those
      reported for Beagles. Bone alkaline phosphatase (BALP) and carboxy-terminal
      telopeptide of type I collagen (ICTP), respectively markers of bone formation and
      bone resorption, were measured in age matched Pomeranians (n=14) and Irish
      Wolfhounds (n=14). No statistically significant differences between the mean BALP
      and mean ICTP serum concentrations from Pomeranians and Irish Wolfhounds were
      found. All BALP and ICTP concentrations were within the reference range reported
      for Beagles. The results of this study suggest that serum BALP and ICTP
      concentrations in giant and toy breeds are the same as in Beagles and that these
      assays may be used for dogs of all sizes.

PMID- 14659730
TI  - Serum paraoxonase activity and lipid parameters in the early postpartum period of
      dairy cows.
AB  - The effect of early lactation on serum paraoxonase activity was studied on 21
      postpartum dairy cows and 19 non-pregnant late lactating dairy cows. A
      significant decrease of the paraoxonase activity was found in the early
      postpartum period compared to the late non-pregnant lactation. The serum
      triglyceride, cholesterol and LDL-cholesterol concentration were also markedly
      reduced during the postpartum period, while the serum HDL-cholesterol
      concentration showed no significant change. The results indicate that lower serum
      paraoxonase activity is associated with lipid metabolic disorders in the early
      postpartum period. A decreased serum paraoxonase activity may lead to the
      reduction of the antioxidative capacity and antioxidative protection during the
      early postpartum period.

PMID- 14659731
TI  - Immunohistochemical localization of the progesterone and oestrogen receptors in
      the shell gland of sexually immature ostriches (Struthio camelus) with active or
      inactive ovaries.
AB  - The immunohistochemical localization of progesterone and oestrogen receptors was
      studied in the shell gland of the immature ostrich (Struthio camelus) during
      periods of ovarian activity and inactivity. In birds with active ovaries moderate
      to strong immunostaining for the progesterone receptor was observed in the
      surface epithelium and tubular glands. In contrast faint progesterone receptor
      immunostaining was observed in the surface epithelium of the shell gland in
      ostriches with inactive ovaries. In addition, bud-like invaginations of the
      surface epithelium, which signaled tubular gland development, were negative for
      the progesterone receptor. Oestrogen receptor immunostaining, which was seen only
      in birds with active ovaries, was weak and restricted to nuclei of the surface
      epithelium. These results suggest that steroid hormones secreted by the active
      ovary regulate the differentiation of the shell gland. Furthermore, the influence
      of these hormones on the shell gland appears to be mediated predominantly through
      the activation of the progesterone receptor.

PMID- 14659732
TI  - Treatment of experimental ureteral strictures by endourological ureterotomy and
      implantation of stents in the porcine animal model.
AB  - The objective of this study is to evaluate the dilation of the ureter using
      endoureterotomy and an expanding-sheath double pigtail ureteral stent in the
      treatment of experimentally induced ureteral strictures in the porcine animal
      model. This is a new treatment in the ureteral strictures resolution in
      Veterinary Urology, although it is not a common affection, it usually appears as
      a consequence of ureteritis and in the iatrogenic female genital surgery. The
      experimental study is design in three phases: induction of experimental
      stricture, diagnosis and treatment of the stricture and follow-up. We have used
      10 healthy Large White female pigs. The internal ureteral diameter was measured
      prior to laparoscopic ligature stricture induction using retrograde
      ureteropyelography (RUPG). Experimental stricture was diagnosed 4 weeks after
      intervention, using RUPG and ultrasound, and treated by endoureterotomy and
      subsequent placement of a double pigtail ureteral stent, which was removed 6
      weeks later. The study finished 4 weeks later with measurement of ureteral
      diameters using RPUG and ultrasound evaluation. Except in one case, all ureters
      displayed permanent dilation of the strictured area for 10 weeks after treatment
      (6 weeks with ureteral stent and 4 more weeks without stent). Finally, this
      technique proved to be effective in cases of short-length and short-living
      ureteral strictures, and represents a viable alternative to conventional surgery
      in animals.

PMID- 14659733
TI  - GC analysis of essential oils in the rumen fluid after incubation of Thuja
      orientalis twigs in the Rusitec system.
AB  - Methods for the chemical analysis of toxic plant substances in the rumen of
      ruminants are of importance for the diagnosis of intoxications with poisonous
      plants. The present work establishes a method to estimate monoterpene components
      of the essential oil of thuja (Thuja orientalis, Cupressaceae) in these types of
      samples. Alpha-thujone, which is regarded as the toxic principle, is present at a
      concentration of 50-60% in the essential oil. The rumen simulation technique
      (Rusitec) was used to simulate natural digestion. Chopped twigs of thuja were
      subjected to rumen content in a closed container with an overflow device. The
      flow of saliva was simulated by the continuous addition of a buffer solution.
      Samples for analysis were taken from the overflow at 24 and 48 h. A further
      sample was taken from the remaining liquid fraction of the rumen content in the
      container at 48 h. The essential oils were extracted with hexane and
      concentrated. A quantitative determination was done by capillary gas
      chromatography. Together in the three fractions analysed this resulted in total
      mean recoveries of 6.8% for alpha-thujone, 5.3% for beta-thujone, 18.9% for
      fenchone and 27.8% for camphor. The observation that the thujones were recovered
      to a lesser extent than other oil components is evidence of their fast
      decomposition in the rumen medium. Under these circumstances the calculated
      detection limit is 100-200 g thuja twigs in cows with rumen volumes of 60-100
      litres. The main essential oil degradation products found in the rumen fluid of
      all three fractions in the Rusitec system were discovered to be iso-3-thujanol,
      neo-3-thujanol, carvomenthol and carvomenthone.

PMID- 14659734
TI  - Transient decrease in blood heterophils and sustained liver damage caused by
      calicivirus infection of young rabbits that are naturally resistant to rabbit
      haemorrhagic disease.
AB  - Young rabbits are naturally resistant to rabbit haemorrhagic disease (RHD) caused
      by the same calicivirus that kills, within 3 days, nearly all adult animals. We
      have investigated changes in blood leukocytes, and in the morphology and
      biochemistry of the liver (the organ where caliciviruses replicate) of young
      rabbits undergoing benign infection by the RHD virus. Four-week-old rabbits were
      infected with a calicivirus inoculum having a titre of 2(12) haemagglutination
      units either sacrificed 18, 24, 48 and 72 h later, or kept for follow-up studies
      up to 21 days after inoculation. The infection caused an acute and transient
      decrease in blood heterophils, and sustained enhancement in hepatic
      transaminases. Inflammatory infiltrates of the liver were seen in all animals
      after 24 h of infection; they had a predominant midlobular location. Hepatocytes
      could present different degrees of cell damage, including cell death; these
      lesions were limited to the liver cells located around the inflammatory
      infiltrates. Liver transaminases peaked 24-48 h after calicivirus infection; this
      was the same timing when liver infiltration and hepatocyte damage were more
      evident. No alterations of other parameters of liver biochemistry were observed.
      We conclude that calicivirus infection of young rabbits causes a subclinical
      disorder characterised by an acute and transient decrease in circulating
      heterophils, and focal liver damage that is expressed by intralobular
      infiltration by heterophils, initially, and, later on, by mononuclear cells. Our
      finding of persistence of increased values of liver transaminases suggests
      chronicity of the infection in young rabbits. We propose that, although resistant
      to RHD, young rabbits infected by calicivirus may be long-term carriers of the
      infectious agent and, thus, become a major source of transmission of the virus.

PMID- 14659736
TI  - The discovery of the DNA double helix.

PMID- 14659737
TI  - Mapping domain structures in silks from insects and spiders related to protein
      assembly.
AB  - The exceptional solubility in vivo (20-30%, w/v) of the silk proteins of insects
      and spiders is dictated by both the need to produce solid fibres with a high
      packing fraction and the high mesogen concentration required for lyotropic liquid
      crystalline spinning. A further design requirement for silk proteins is a strong
      predominance of hydrophobic amino acid residues to provide for the hydrophobic
      interactions, water exclusion, and beta-crystallite formation required to produce
      strong insoluble threads. Thus, the domain structure of silk proteins needs to
      enable nanoscale phase separation to achieve high solubility of hydrophobic
      proteins in aqueous solutions. Additionally, silk proteins need to avoid
      premature precipitation as beta-sheets during storage and processing. Here we use
      mapping of domain types, sizes and distributions in silks to identify consistent
      design features that have evolved to meet these requirements. We show that silk
      proteins consist of conspicuously hydrophilic terminal domains flanking a very
      long central portion constructed from hydrophobic blocks separated by hydrophilic
      ones, discussing the domain structure in detail. The general rules of
      construction for silk proteins based on our observations should give a useful
      guide to the way in which Nature has solved the problem of processing hydrophobic
      proteins in water and how this can be copied industrially. Following these rules
      may also help in obtaining adequate expression, soluble products and controllable
      conformational switches in the production of genetically engineered or chemically
      synthesized silk analogues. Thus these insights have implications for structural
      biology and relevance to fundamental and applied questions in material science
      and engineering.

PMID- 14659738
TI  - Optimization of the antibody C(H)3 domain by residue frequency analysis of IgG
      sequences.
AB  - In an attempt to enhance the overall assembly, yield and half-life of recombinant
      antibody proteins, we have cloned and expressed several IgG1 C(H)3 domains and
      examined their folding/refolding characteristics. We utilized a cytoplasmic
      bacterial expression system with a thioredoxin reductase knock-out strain of
      BL21(DE3) to produce bovine, murine and human C(H)3. Under identical conditions,
      expression of bovine C(H)3 resulted consistently in the highest yields of
      properly folded/oxidized protein. Circular dichroism and fluorescence experiments
      demonstrate that oxidized bovine and murine C(H)3 have surprisingly similar
      structures and stabilities, considering the marginal sequence conservation
      between the two molecules. Residue frequency analysis using a limited data set of
      36 unique Fc sequences originating from 19 different mammalian species targeted
      five specific sites for optimization within bovine C(H)3. Combination of three of
      these mutants increased the thermal stability of the molecule to 86 degrees C.
      Comparison of this approach to similar studies using larger sequence databases
      and/or different selection criteria suggests sequence database design can
      increase the success rate for identifying residue sites worth optimizing. This
      optimized C(H)3 domain can be used as a particularly stable platform for
      functional design and can be grafted into full-length antibody sequences to
      enhance their thermodynamic parameters and shelf-life.

PMID- 14659739
TI  - Pentamerization of single-domain antibodies from phage libraries: a novel
      strategy for the rapid generation of high-avidity antibody reagents.
AB  - We describe a novel type of molecule in which single-domain antibodies (sdAbs)
      isolated from a nai;ve llama single domain antibody library are linked to an
      oligomerization domain to generate high-avidity, antigen-binding reagents. An
      sdAb is fused to the B-subunit of Escherichia coli verotoxin, or shiga-like
      toxin, which self-assembles to form a homopentamer and results in simultaneous
      sdAb pentamerization and introduction of avidity. Molecular modeling indicated
      that this fusion protein (PDB: 1OJF), termed pentabody, has structural
      flexibility for binding to surface-presented antigen. In the instance of an sdAb
      specific for a peptide antigen, pentamerization resulted in a dramatic increase
      in functional affinity for immobilized antigen. The pentabody was expressed in
      high yield in E.coli in a non-aggregated state, and exhibited excellent
      thermostability and protease resistance. This technology provides a relatively
      rapid means of generating novel antigen-binding molecules that bind strongly to
      immobilized antigen. It is expected that pentavalent sdAbs will have general
      applicability in proteomics, immunochemical staining, cancer diagnosis and other
      applications in which antigens are presented multivalently.

PMID- 14659740
TI  - A distal, high-affinity binding site on the cyclin-CDK substrate Pho4 is
      important for its phosphorylation and regulation.
AB  - Cyclins and cyclin-dependent kinases (CDKs) are key components of signaling
      pathways essential for cell growth and survival. The cyclin-CDK Pho80-Pho85
      inactivates the transcription factor Pho4 in budding yeast by phosphorylating it
      on five sites. We isolated seven single amino acid substitutions outside of the
      phosphorylation sites that cause Pho4 to be constitutively active. The
      substitutions decrease the amount of Pho4 phosphorylation in vivo, and they
      increase the apparent K(M) of the in vitro phosphorylation reaction by an order
      of magnitude but do not alter k(cat) substantially. These data suggest that the
      substituted residues are part of a cyclin-CDK-binding site that is distal to the
      phosphorylation sites. Further analysis revealed that all of Pho4 variants were
      phosphorylated by Pho80-Pho85 in a more distributive manner than the wild-type
      protein, further supporting the idea that binding at a distal, high-affinity
      binding site is important in determining the processivity of Pho4
      phosphorylation. In addition, computational modeling of the Pho4 phosphorylation
      reactions shows that the K(D) of binding between the Pho4 mutants and Pho80-Pho85
      increases, confirming that the mutations are located in a relatively high
      affinity "docking site" for the kinase. Interestingly, the K(D) derived from the
      in vitro data correlates well with the strength of the in vivo phenotypes,
      demonstrating that the in vitro data are relevant to the in vivo regulation of
      Pho4.

PMID- 14659741
TI  - Reinitiation and recycling are distinct processes occurring downstream of
      translation termination in yeast.
AB  - The circularisation model of the polysome suggests that ribosome recycling is
      facilitated by 5'-3' interactions mediated by the cap-binding complex eIF4F and
      the poly(A)-binding protein, Pab1. Alternatively, downstream of a short upstream
      open reading frame (uORF) in the 5' untranslated region of a gene,
      posttermination ribosomes can maintain the competence to (re)initiate
      translation. Our data show that recycling and reinitiation must be distinct
      processes in Saccharomyces cerevisiae. The role of the 3'UTR in recycling was
      assessed by restricting ribosome movement along the mRNA using a poly(G) stretch
      or the mammalian iron regulatory protein bound to the iron responsive element. We
      find that although 3'UTR structure can influence translation, the main pathway of
      ribosome recycling does not depend on scanning-like movement through the 3'UTR.
      Changes in termination kinetics or disruption of the Pab1-eIF4F interaction do
      not affect recycling, yet the maintenance of normal in vivo mRNP structure is
      important to this process. Using bicistronic ACT1-LUC constructs, elongating
      yeast ribosomes were found to maintain the competence to (re)initiate over only
      short distances. Thus, as the first ORF to be translated is progressively
      truncated, reinitiation downstream of an uORF of 105nt is found to be just
      detectable, and increases markedly in efficiency as uORF length is reduced to
      15nt. Experiments using a strain mutated in the Cca1 nucleotidyltransferase
      suggest that the uORF length-dependence of changes in reinitiation competence is
      affected by peptide elongation kinetics, but that ORF length per se may also be
      relevant.

PMID- 14659742
TI  - Crystal structure of the RluD pseudouridine synthase catalytic module, an enzyme
      that modifies 23S rRNA and is essential for normal cell growth of Escherichia
      coli.
AB  - Pseudouridine (5-beta-D-ribofuranosyluracil, Psi) is the most commonly found
      modified base in RNA. Conversion of uridine to Psi is performed enzymatically in
      both prokaryotes and eukaryotes by pseudouridine synthases (EC 4.2.1.70). The
      Escherichia coli Psi-synthase RluD modifies uridine to Psi at positions 1911,
      1915 and 1917 within 23S rRNA. RluD also possesses a second function related to
      proper assembly of the 50S ribosomal subunit that is independent of Psi
      synthesis. Here, we report the crystal structure of the catalytic module of RluD
      (residues 68-326; DeltaRluD) refined at 1.8A to a final R-factor of 21.8%
      (R(free)=24.3%). DeltaRluD is a monomeric enzyme having an overall mixed
      alpha/beta fold. The DeltaRluD molecule consists of two subdomains, a catalytic
      subdomain and C-terminal subdomain with the RNA-binding cleft formed by loops
      extending from the catalytic sub-domain. The catalytic sub-domain of DeltaRluD
      has a similar fold as in TruA, TruB and RsuA, with the location of the RNA
      binding cleft, active-site and conserved, catalytic Asp residue superposing in
      all four structures. Superposition of the crystal structure of TruB bound to a T
      stem loop with RluD reveals that similar RNA-protein interactions for the flipped
      out uridine base would exist in both structures, implying that base-flipping is
      necessary for catalysis. This observation also implies that the specificity
      determinants for site-specific RNA-binding and recognition likely reside in parts
      of RluD beyond the active site.

PMID- 14659743
TI  - Regulation of RNA polymerase promoter selectivity by covalent modification of
      DNA.
AB  - Expression of genes encoding type II restriction/modification (R/M) systems,
      which are widely spread in eubacteria, must be tightly regulated to ensure that
      host DNA is protected from restriction endonucleases at all times. Examples of
      coordinated expression of R/M genes that rely on the action of regulatory factors
      or the ability of methyl transferases to repress their own synthesis by
      interacting with the promoter DNA have been described. Here, we characterize the
      molecular mechanism of factor-independent regulation in the CfrBI R/M system.
      Regulation of the cfrBIM gene transcription occurs through CfrBIM-catalyzed
      methylation of a cytosine residue in the cfrBIM promoter. The covalent
      modification inhibits cfrB1M promoter complex formation by interfering with the
      RNA polymerase sigma(70) subunit region 4.2 recognition of the -35 promoter
      element. The decrease in the cfrBIM promoter complex formation leads to increase
      in the activity of overlapping cfrBIR promoters. This elegant factor-independent
      regulatory system ensures coordinated expression of the cfrBI genes.

PMID- 14659744
TI  - A thermodynamic basis of DNA sequence selectivity by the ETS domain of murine
      PU.1.
AB  - The ETS domain of the transcription factor PU.1 tolerates a large number of DNA
      cognate variants that differ exclusively in the sequences flanking a critical
      central consensus, 5'-GGAA-3'. We investigated the thermodynamics of site
      selection by the DNA-binding domain by following the PU.1 ETS/DNA equilibrium
      with a large set of cognate variants under various temperature and salt
      conditions by filter binding. Our results indicate that the stability of the
      ETS/DNA complex is quantitatively tied to variations in the change in heat
      capacity. Thermodynamic effects induced by changing Na(+) concentrations from 150
      mM to 250 mM are complex and not readily interpreted by polyelectrolyte theory.
      We also extended our understanding of data from our previous investigation on
      energetic base-neighbour coupling, by dissecting the thermodynamic contributions
      underlying the observed free-energy coupling. In conjunction with available
      structural and biochemical data, we propose that site selectivity by the PU.1 ETS
      domain arises from differential protein/DNA contacts in the flanking sequences
      that modulate the orientation of the ETS recognition helix and trigger a coupled
      reduction in the flexibility observed in the unbound ETS domain.

PMID- 14659745
TI  - Crystal structure of the catalytic domain of human ADAM33.
AB  - Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored
      metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and
      metalloprotease) are a family of glycoproteins implicated in cell-cell
      interactions, cell fusion, and cell signaling. We have determined the crystal
      structure of the Adam33 catalytic domain in complex with the inhibitor marimastat
      and the inhibitor-free form. The structures reveal the polypeptide fold and
      active site environment resembling that of other metalloproteases. The substrate
      binding site contains unique features that allow the structure-based design of
      specific inhibitors of this enzyme.

PMID- 14659746
TI  - Complex formation with kinesin motor domains affects the structure of
      microtubules.
AB  - Microtubules are highly dynamic components of the cytoskeleton. They are
      important for cell movement and they are involved in a variety of transport
      processes together with motor proteins, such as kinesin. The exact mechanism of
      these transport processes is not known and so far the focus has been on
      structural changes within the motor domains, but not within the underlying
      microtubule structure. Here we investigated the interaction between kinesin and
      tubulin and our experimental data show that microtubules themselves are changing
      structure during that process. We studied unstained, vitrified samples of
      microtubules composed of 15 protofilaments using cryo electron microscopy and
      helical image analysis. 3D maps of plain microtubules and microtubules decorated
      with kinesin have been reconstructed to approximately 17A resolution. The
      alphabeta-tubulin dimer could be identified and, according to our data, alpha-
      and beta-tubulin adopt different conformations in plain microtubules. Significant
      differences were detected between maps of plain microtubules and microtubule
      kinesin complexes. Most pronounced is the continuous axial inter-dimer contact in
      the microtubule-kinesin complex, suggesting stabilized protofilaments along the
      microtubule axis. It seems, that mainly structural changes within alpha-tubulin
      are responsible for this observation. Lateral effects are less pronounced.
      Following our data, we believe, that microtubules play an active role in
      intracellular transport processes through modulations of their core structure.

PMID- 14659747
TI  - Crystal structure of beta-D-xylosidase from Thermoanaerobacterium
      saccharolyticum, a family 39 glycoside hydrolase.
AB  - 1,4-beta-D-Xylan is the major component of plant cell-wall hemicelluloses. beta-D
      Xylosidases are involved in the breakdown of xylans into xylose and belong to
      families 3, 39, 43, 52, and 54 of glycoside hydrolases. Here, we report the first
      crystal structure of a member of family 39 glycoside hydrolase, i.e. beta-D
      xylosidase from Thermoanaerobacterium saccharolyticum strain B6A-RI. This study
      also represents the first structure of any beta-xylosidase of the above five
      glycoside hydrolase families. Each monomer of T. saccharolyticum beta-xylosidase
      comprises three distinct domains; a catalytic domain of the canonical
      (beta/alpha)(8)-barrel fold, a beta-sandwich domain, and a small alpha-helical
      domain. We have determined the structure in two forms: D-xylose-bound enzyme and
      a covalent 2-deoxy-2-fluoro-alpha-D-xylosyl-enzyme intermediate complex, thus
      providing two snapshots in the reaction pathway. This study provides structural
      evidence for the proposed double displacement mechanism that involves a covalent
      intermediate. Furthermore, it reveals possible functional roles for His228 as the
      auxiliary acid/base and Glu323 as a key residue in substrate recognition.

PMID- 14659748
TI  - Crystal structure of echicetin from Echis carinatus (Indian saw-scaled viper) at
      2.4A resolution.
AB  - Echicetin is a heterodimeric protein from the venom of the Indian saw-scaled
      viper, Echis carinatus. It binds to platelet glycoprotein Ib (GPIb) and thus
      inhibits platelet aggregation. It has two subunits, alpha and beta, consisting of
      131 and 123 amino acid residues, respectively. The two chains are linked with a
      disulphide bond. The level of amino acid sequence homology between two subunits
      is 50%. The protein was purified from the venom of E.carinatus and crystallized
      using ammonium sulphate as a precipitant. The crystal structure has been
      determined at 2.4A resolution and refined to an R-factor of 0.187. Overall
      dimensions of the heterodimer are approximately 80Ax35Ax35A. The backbone folds
      of the two subunits are similar. The central portions of the polypeptide chains
      of alpha and beta-subunits move into each other to form a tight dimeric
      association. The remaining portions of the chains of both subunits fold in a
      manner similar to those observed in the carbohydrate-binding domains of C-type
      lectins. In echicetin, the Ca(2+)-binding sites are not present, despite being
      topologically equivalent to other similar Ca(2+)-binding proteins of the
      superfamily. The residues Ser41, Glu43 and Glu47 in the calcium-binding proteins
      of the related family are conserved but the residues Glu126/120 are replaced by
      lysine at the corresponding sites in the alpha and beta-subunits.

PMID- 14659749
TI  - A human synthetic combinatorial library of arrayable single-chain antibodies
      based on shuffling in vivo formed CDRs into general framework regions.
AB  - We describe a novel approach for high-throughput screening of recombinant
      antibodies, based on their immobilization on solid cellulose-based supports. We
      constructed a large human synthetic single-chain Fv antibody library where in
      vivo formed complementarity determining regions were shuffled combinatorially
      onto germline-derived human variable-region frameworks. The arraying of library
      derived scFvs was facilitated by our unique display/expression system, where
      scFvs are expressed as fusion proteins with a cellulose-binding domain (CBD).
      Escherichia coli cells expressing library-derived scFv-CBDs are grown on a porous
      master filter on top of a second cellulose-based filter that captures the
      antibodies secreted by the bacteria. The cellulose filter is probed with labeled
      antigen allowing the identification of specific binders and the recovery of the
      original bacterial clones from the master filter. These filters may be
      simultaneously probed with a number of antigens allowing the isolation of a
      number of binding specificities and the validation of specificity of binders. We
      screened the library against a number of cancer-related peptides, proteins, and
      peptide-protein complexes and yielded antibody fragments exhibiting dissociation
      constants in the low nanomolar range. We expect our new antibody phage library to
      become a valuable source of antibodies to many different targets, and to play a
      vital role in facilitating high-throughput target discovery and validation in the
      area of functional cancer genomics.

PMID- 14659750
TI  - Direct phage to intrabody screening (DPIS): demonstration by isolation of
      cytosolic intrabodies against the TES1 site of Epstein Barr virus latent membrane
      protein 1 (LMP1) that block NF-kappaB transactivation.
AB  - The expression of intracellular antibodies (intrabodies) in eukaryotic cells has
      provided a powerful tool to manipulate microbial and cellular signaling pathways
      in a highly precise manner. However, there have been several technical issues
      that have restricted their more widespread use. In particular, single-chain
      antibodies (sFv) have been reported to fold poorly in the reducing environment of
      the cytoplasm and as such there has been a reluctance to use sFv-phage libraries
      as a source of intrabodies unless a pre-selection step to identify these rare
      sFvs from natural libraries or libraries of engineering sFvs that could fold
      properly in the absence of disulfide bonds were used. Here, we investigated
      whether target specific sFvs that are isolated from a 15 billion member non
      immune human sFv-phage display library could be directly screened in pools as
      intrabodies without prior knowledge of their individual identity or purity within
      pools of antigen-specific sFvs. As the target, we used a synthetic transformation
      effector site 1 (TES1) polypeptide comprising the membrane-most proximal 34 amino
      acid residues of the carboxy-terminal cytoplasmic tail of the oncogenic latent
      membrane protein 1 (LMP1) of Epstein Barr virus, which serves as a docking site
      for adapter proteins of the tumor necrosis factor (TNF) receptor (TNFR)
      associated factor (TRAF) family. Anti-TES1 sFvs, initially identified by phage
      ELISA screens, were grouped into pools according to the absorbance reading of the
      antigen-specific phage ELISA assays and then transferred as pools into eukaryotic
      expression vectors and expressed as cytoplasmic intrabodies. Using the pooling
      strategy, there was no loss of individual anti-TES1 sFvs in the transfer from
      prokaryotic to eukaryotic expression vectors. In addition, the initial
      assignments into sFv pools based on phage ELISA readings allowed the segregation
      of individual anti-TES1 sFvs into discrete or minimally overlapping intrabody
      pools. Further assessment of the biological activity of the anti-TES1 intrabody
      pools demonstrated that they were all able to selectively block F-LMP1-induced
      NFkappaB activity that was mediated through the TES1-site and to bind LMP1
      protein with high efficiency. This direct phage to intrabody screening (DPIS)
      strategy should allow investigators to bypass much of the in vitro sFv
      characterization that is often not predictive of in vivo intrabody function and
      provide a more efficient use of large native and synthetic sFv phage libraries
      already in existence to identify intrabodies that are active in vivo.

PMID- 14659751
TI  - Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody
      by random mutagenesis and sequential antigen panning.
AB  - Several human monoclonal antibodies can neutralize a range of human
      immunodeficiency virus type 1 (HIV-1) primary isolates but their potency and
      related ability to suppress generation of HIV-1 escape mutants is significantly
      lower than the activity of antiretroviral drugs currently in clinical use.
      Recently, a human Fab, X5, was identified and found to neutralize primary
      isolates from different clades. Further improvement of the potency and breadth of
      HIV-1 neutralization by this antibody could be critical for its potential use in
      the treatment of HIV-1-infected patients. However, increasing potency of an
      antibody by selection from libraries may lead to a decrease in the breadth of
      neutralization. In an attempt to solve this problem, we subjected a random
      mutagenesis library of the scFv X5 to sequential rounds of selection on non
      homologous HIV-1 envelope glycoproteins (Envs) dubbed sequential antigen panning
      (SAP). By using SAP, we identified two scFv antibodies, m6 and m9, that were
      tested with a panel of 33 diverse primary HIV-1 infectious isolates in an assay
      based on a reporter cell-line expressing high levels of CD4, CCR5 and CXCR4. The
      IC(50) was less than 50 microg/ml for 21 (m6) and 19 (m9) out of 29 isolates from
      group M (subtypes A-C, F, G and CRF-01AE) and one isolate from group N; three
      isolates from group O were not significantly inhibited at 50 microg/ml. The
      average IC(50) values for the two antibodies were significantly (p<0.001, n=29)
      lower compared to scFv X5. Their inhibitory activity does not appear to be
      related to the HIV-1 subtype, coreceptor usage or the disease stage. m9 inhibited
      infection of peripheral blood mononuclear cells by the primary isolates JRCSF,
      89.6 and BR020 with IC(90) of 4, 6 and 25 microg/ml, respectively; for a single
      round infection by pseudovirus, the IC(90) for JRSCF, 89.6, YU2 and HXBc2 was 15,
      5, 15 and 5 microg/ml, respectively. In these two assays the IC(90) for m9 was,
      on average, two- to threefold lower than for scFv X5. These results demonstrate
      that both the potency and the breadth of HIV-1 neutralization of one of the few
      known potent broadly cross-reactive human monoclonal antibodies, scFv X5, could
      be improved significantly. However, only experiments in animal models and
      clinical trials in humans will show whether these new scFvs and the approach for
      their identification have potential in the development of prophylactics and
      therapeutics for HIV-1 infections.

PMID- 14659752
TI  - The mechanism of insulin action on islet amyloid polypeptide fiber formation.
AB  - The pathology of type II diabetes includes the presence of cytotoxic amyloid
      deposits in the islets of Langerhans. The main component of these deposits, islet
      amyloid polypeptide (IAPP), is a hormone involved in glucose metabolism and is
      normally co-secreted with insulin by the beta-cells of the pancreas. Here, we
      perform in vitro IAPP fibrillogenesis experiments in the presence and in the
      absence of insulin to elucidate the mechanism by which insulin acts on fiber
      formation. We find that insulin is an exceptionally potent inhibitor. In contrast
      to the vast excess of insulin over IAPP in vivo, substoichiometric amounts of
      insulin inhibit seeded and unseeded reactions by more than tenfold in vitro.
      Unusually, the magnitude of the inhibitory effect is dependent on the
      concentration of insulin, yet independent of the concentration of IAPP. In
      addition, insulin appears to bind non-specifically to fiber surfaces, giving rise
      to altered morphology. IAPP fiber formation in vitro requires a minimum of three
      steps: fiber-independent nucleation, elongation, and fiber-dependent nucleation.
      Furthermore, these steps are attenuated by the presence of a dispersed-phase
      transition. We interpret these data in the context of the phase-mediated
      fibrillogenesis model (PMF) and conclude through experiment and kinetic
      simulation that the dominant effect of insulin is to act on the elongation
      portion of the reaction. These results suggest that amyloid formation in type II
      diabetes involves either an additional agent that acts as an accelerant, or a
      step that segregates IAPP from insulin.

PMID- 14659753
TI  - Crystal structures of the Rhodococcus proteasome with and without its pro
      peptides: implications for the role of the pro-peptide in proteasome assembly.
AB  - To understand the role of the pro-peptide in proteasome assembly, we have
      determined structures of the Rhodococcus proteasome and a mutant form that
      prevents the autocatalytic removal of its pro-peptides. The structures reveal
      that the pro-peptide acts as an assembly-promoting factor by linking its own beta
      subunit to two adjacent alpha-subunits, thereby providing a molecular explanation
      for the observed kinetics of proteasome assembly. The Rhodococcus proteasome has
      been found to have a substantially smaller contact region between alpha-subunits
      compared to those regions in the proteasomes of Thermoplasma, yeast, and
      mammalian cells, suggesting that a smaller contact area between alpha-subunits is
      likely the structural basis for the Rhodococcus alpha-subunits not assembling
      into alpha-rings when expressed alone. Analysis of all available beta-subunit
      structures shows that the contact area between beta-subunits within a beta-ring
      is not sufficient for beta-ring self-assembly without the additional contact
      provided by the alpha-ring. This appears to be a fail-safe mechanism ensuring
      that the active sites on the beta-subunits are activated only after proteasome
      assembly is complete.

PMID- 14659754
TI  - Solid state NMR reveals a pH-dependent antiparallel beta-sheet registry in
      fibrils formed by a beta-amyloid peptide.
AB  - We report solid state nuclear magnetic resonance (NMR) measurements that probe
      the supramolecular organization of beta-sheets in the cross-beta motif of amyloid
      fibrils formed by residues 11-25 of the beta-amyloid peptide associated with
      Alzheimer's disease (Abeta(11-25)). Fibrils were prepared at pH 7.4 and pH 2.4.
      The solid state NMR data indicate that the central hydrophobic segment of
      Abeta(11-25) (sequence LVFFA) adopts a beta-strand conformation and participates
      in antiparallel beta-sheets at both pH values, but that the registry of
      intermolecular hydrogen bonds is pH-dependent. Moreover, both registries
      determined for Abeta(11-25) fibrils are different from the hydrogen bond registry
      in the antiparallel beta-sheets of Abeta(16-22) fibrils at pH 7.4 determined in
      earlier solid state NMR studies. In all three cases, the hydrogen bond registry
      is highly ordered, with no detectable "registry-shift" defects. These results
      suggest that the supramolecular organization of beta-sheets in amyloid fibrils is
      determined by a sensitive balance of multiple side-chain-side-chain interactions.
      Recent structural models for Abeta(11-25) fibrils based on X-ray fiber
      diffraction data are inconsistent with the solid state NMR data at both pH
      values.

PMID- 14659755
TI  - X-ray structures of the maltose-maltodextrin-binding protein of the
      thermoacidophilic bacterium Alicyclobacillus acidocaldarius provide insight into
      acid stability of proteins.
AB  - Maltose-binding proteins act as primary receptors in bacterial transport and
      chemotaxis systems. We report here crystal structures of the thermoacidostable
      maltose-binding protein from Alicyclobacillus acidocaldarius, and explore its
      modes of binding to maltose and maltotriose. Further, comparison with the
      structures of related proteins from Escherichia coli (a mesophile), and two
      hyperthermophiles (Pyrococcus furiosus and Thermococcus litoralis) allows an
      investigation of the basis of thermo- and acidostability in this family of
      proteins.The thermoacidophilic protein has fewer charged residues than the other
      three structures, which is compensated by an increase in the number of polar
      residues. Although the content of acidic and basic residues is approximately
      equal, more basic residues are exposed on its surface whereas most acidic
      residues are buried in the interior. As a consequence, this protein has a highly
      positive surface charge. Fewer salt bridges are buried than in the other MBP
      structures, but the number exposed on its surface does not appear to be unusual.
      These features appear to be correlated with the acidostability of the A.
      acidocaldarius protein rather than its thermostability. An analysis of cavities
      within the proteins shows that the extremophile proteins are more closely packed
      than the mesophilic one. Proline content is slightly higher in the
      hyperthermophiles and thermoacidophiles than in mesophiles, and this amino acid
      is more common at the second position of beta-turns, properties that are also
      probably related to thermostability. Secondary structural content does not vary
      greatly in the different structures, and so is not a contributing factor.

PMID- 14659756
TI  - Dimeric rous sarcoma virus capsid protein structure relevant to immature Gag
      assembly.
AB  - The structure of the N-terminal domain (NTD) of Rous sarcoma virus (RSV) capsid
      protein (CA), with an upstream 25 amino acid residue extension corresponding to
      the C-terminal portion of the Gag p10 protein, has been determined by X-ray
      crystallography. Purified Gag proteins of retroviruses can assemble in vitro into
      virus-like particles closely resembling in vivo-assembled immature virus
      particles, but without a membrane. When the 25 amino acid residues upstream of CA
      are deleted, Gag assembles into tubular particles. The same phenotype is observed
      in vivo. Thus, these residues act as a "shape determinant" promoting spherical
      assembly, when they are present, or tubular assembly, when they are absent. We
      show that, unlike the NTD on its own, the extended NTD protein has no beta
      hairpin loop at the N terminus of CA and that the molecule forms a dimer in which
      the amino-terminal extension forms the interface between monomers. Since
      dimerization of Gag has been inferred to be a critical step in assembly of
      spherical, immature Gag particles, the dimer interface may represent a structural
      feature that is essential in retrovirus assembly.

PMID- 14659757
TI  - A conserved arginine plays a role in the catalytic cycle of the protein
      disulphide isomerases.
AB  - The pK(a) values of the CXXC active-site cysteine residues play a critical role
      in determining the physiological function of the thioredoxin superfamily. To act
      as an efficient thiol-disulphide oxidant the thiolate state of the N-terminal
      cysteine must be stabilised and the thiolate state of the C-terminal cysteine
      residue destabilised. While increasing the pK(a) value of the C-terminal cysteine
      residue promotes oxidation of substrates, it has an inhibitory effect on the
      reoxidation of the enzyme, which is promoted by the formation of a thiolate at
      this position. Since reoxidation is essential to complete the catalytic cycle,
      the differential requirement for a high and a low pK(a) value for the C-terminal
      cysteine residue for different steps in the reaction presents us with a paradox.
      Here, we report the identification of a conserved arginine residue, located in
      the loop between beta5 and alpha4 of the catalytic domains of the human protein
      disulphide isomerase (PDI) family, which is critical for the catalytic function
      of PDI, ERp57, ERp72 and P5, specifically for reoxidation. An examination of the
      published NMR structure for the a domain of PDI combined with molecular dynamic
      studies suggest that the side-chain of this arginine residue moves into and out
      of the active-site locale and that this has a very marked effect on the pK(a)
      value of the active-site cysteine residues. This intra-domain motion resolves the
      apparent dichotomy of the pK(a) requirements for the C-terminal active-site
      cysteine.

PMID- 14659758
TI  - Side-chain contributions to membrane protein structure and stability.
AB  - The molecular forces that stabilize membrane protein structure are poorly
      understood. To investigate these forces we introduced alanine substitutions at 24
      positions in the B helix of bacteriorhodopsin and examined their effects on
      structure and stability. Although most of the results can be rationalized in
      terms of the folded structure, there are a number of surprises. (1) We find a
      remarkably high frequency of stabilizing mutations (17%), indicating that
      membrane proteins are not highly optimized for stability. (2) Helix B is kinked,
      with the kink centered around Pro50. The P50A mutation has no effect on
      stability, however, and a crystal structure reveals that the helix remains bent,
      indicating that tertiary contacts dominate in the distortion of this helix. (3)
      We find that the protein is stabilized by about 1kcal/mol for every 38A(2) of
      surface area buried, which is quite similar to soluble proteins in spite of their
      dramatically different environments. (4) We find little energetic difference, on
      average, in the burial of apolar surface or polar surface area, implying that van
      der Waals packing is the dominant force that drives membrane protein folding.

PMID- 14659759
TI  - Crystal structure of type IIE restriction endonuclease EcoRII reveals an
      autoinhibition mechanism by a novel effector-binding fold.
AB  - EcoRII is a type IIE restriction endonuclease that interacts with two copies of
      the DNA recognition sequence 5'CCWGG, one being the actual target of cleavage,
      the other serving as the allosteric effector. The mode of enzyme activation by
      effector binding is unknown. To investigate the molecular basis of activation and
      cleavage mechanisms by EcoRII, the crystal structure of EcoRII mutant R88A has
      been solved at 2.1A resolution. The EcoRII monomer has two domains linked through
      a hinge loop. The N-terminal effector-binding domain has a novel DNA recognition
      fold with a prominent cleft. The C-terminal catalytic domain has a restriction
      endonuclease-like fold. Structure-based sequence alignment identified the
      putative catalytic site of EcoRII that is spatially blocked by the N-terminal
      domain. The structure together with the earlier characterized EcoRII enzyme
      activity enhancement in the absence of its N-terminal domain reveal an
      autoinhibition/activation mechanism of enzyme activity mediated by a novel
      effector-binding fold. This is the first case of autoinhibition, a mechanism
      described for many transcription factors and signal transducing proteins, of a
      restriction endonuclease.

PMID- 14659760
TI  - Specific interaction of the antiapoptotic protein Nr-13 with phospholipid
      monolayers is prevented by the BH3 domain of Bax.
AB  - Members of the Bcl-2 protein family regulate apoptosis by controlling the release
      of apoptogenic proteins such as cytochrome c from the mitochondrial intermembrane
      space. Proapoptotic members induce release by increasing outer membrane
      permeability, while antiapoptotic members prevent this. The activity of Bcl-2
      proteins depends mostly on their insertion into the mitochondrial membrane, which
      is reported to occur via putative channels formed by the two central hydrophobic
      helices. The pro- and antiapoptotic activity of Bcl-2 proteins can also be
      modulated by heterodimerization between antagonists through the BH3 domain of
      proapoptotic members, though the position of the heterodimer with respect to the
      membrane has never been elucidated. In this work, the membrane insertion capacity
      of the antiapoptotic Bcl-2 related protein Nr-13 was explored, using monolayer
      expansion measurements. Nr-13 penetrates into the monolayer with a molecular
      cross-section of 1100A(2), thereby implicating almost all alpha-helical domains
      of the molecule in this process. A mutant protein, bearing neutral instead of
      acidic residues in the loop between the two putative channel-forming fifth and
      sixth alpha-helices, retained the ability to interact with the lipid monolayer,
      suggesting that the membrane insertion of Nr-13 is not exclusively alpha5-alpha6
      dependent. In contrast, the specific interaction of Nr-13 with the monolayer was
      prevented by heterodimer formation with the BH3 domain of proapoptotic Bax. These
      findings are discussed in terms of a model for monolayer insertion in which the
      antiapoptotic Nr-13 and proapoptotic proteins exert their antagonistic effects by
      preventing each other from reaching the membrane.

PMID- 14659761
TI  - Destabilization of a non-pathological variant of ataxin-3 results in
      fibrillogenesis via a partially folded intermediate: a model for misfolding in
      polyglutamine disease.
AB  - Ataxin-3 is a member of the polyglutamine family of proteins, which are
      associated with at least nine different neurodegenerative diseases. In the
      disease state, expansion of the polyglutamine tract leads to dysfunction and
      death of neurons, as well as formation of proteinaceous aggregates known as
      nuclear inclusions. Intriguingly, both expanded and non-expanded forms of ataxin
      3 are observed within these nuclear inclusions. Ataxin-3 is the smallest of the
      polyglutamine disease proteins and in its expanded form causes the
      neurodegenerative disorder Machado-Joseph disease. Using a non-pathological
      variant containing 28 residues in its polyglutamine tract, we have probed the
      folding and misfolding pathways of ataxin-3. We describe here the first
      equilibrium folding pathway delineated for any polyglutamine protein and show
      that ataxin-3 folds reversibly via a single intermediate species. We have also
      explored further the misfolding potential of the protein and found that partial
      destabilization of ataxin-3 by chemical denaturation leads to the formation of
      fibrillar aggregates by the non-pathological variant. These results provide an
      insight into the possible mechanisms by which polyglutamine expansion may affect
      the stability and conformation of the protein. The implications of this are
      considered in the wider context of the development and pathogenesis of
      polyglutamine diseases.

PMID- 14659762
TI  - The 2.9A resolution crystal structure of malate dehydrogenase from Archaeoglobus
      fulgidus: mechanisms of oligomerisation and thermal stabilisation.
AB  - The crystal structure of malate dehydrogenase from the hyperthermophilic archaeon
      Archeoglobus fulgidus, in complex with its cofactor NAD, was solved at 2.9A
      resolution. The crystal structure shows a compact homodimer with one coenzyme
      bound per subunit. The substrate binding site is occupied by a sulphate ion. In
      order to gain insight into adaptation mechanisms, which allow the protein to be
      stable and active at high temperatures, the 3D structure was compared to those of
      several thermostable and hyperthermostable homologues, and to halophilic malate
      dehydrogenase. The hyperthermostable A. fulgidus MalDH protein displays a
      reduction of the solvent-exposed surface, an optimised compact hydrophobic core,
      a high number of hydrogen bonds, and includes a large number of ion pairs at the
      protein surface. These features occur concomitantly with a reduced number of
      residues in the protein subunit, due to several deletions in loop regions. The
      loops are further stiffened by ion pair links with secondary structure elements.
      A. fulgidus malate dehydrogenase is the only dimeric protein known to date that
      belongs to the [LDH-like] MalDH family. All the other known members of this
      family are homo-tetramers. The crystal structures revealed that the association
      of the dimers to form tetramers is prevented by several deletions, taking place
      at the level of two loops that are known to be essential for the tetramerisation
      process within the LDH and [LDH-like] MalDH enzymes.

PMID- 14659763
TI  - Analysis of thermal adaptation in the HSL enzyme family.
AB  - The recently solved three-dimensional (3D) structures of two thermostable members
      of the carboxylesterase/lipase HSL family, namely the Alicyclobacillus (formerly
      Bacillus) acidocaldarius and Archaeoglobus fulgidus carboxylesterases (EST2 and
      AFEST, respectively) were compared with that of the mesophilic homologous
      counterpart Brefeldine A esterase from Bacillus subtilis. Since the 3D homology
      models of other members of the HSL family were also available, we performed a
      structural alignment with all these sequences. The resulting alignment was used
      to assess the amino acid "traffic rule" in the HSL family. Quite surprisingly,
      the data were in very good agreement with those recently reported from two
      independent groups and based on the comparison of a huge number of homologous
      sequences from the genus Bacillus, Methanococcus and Deinococcus/Thermus. Taken
      as a whole, the data point to the statistical meaning of defined amino acid
      conversions going from psychrophilic to hyperthermophilic sequences. We
      identified and mapped several such changes onto the EST2 structure and observed
      that such mutations were localized mostly in loops regions or alpha-helices and
      were mostly excluded from the active site. A site-directed mutagenesis of two of
      the identified residues confirmed they were involved in thermal stability.

PMID- 14659764
TI  - Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment
      from hNIFK reveal unique recognition sites and new views to the structural basis
      of FHA domain functions.
AB  - Recent studies by use of short phosphopeptides showed that forkhead-associated
      (FHA) domains recognize pTXX(D/I/L) motifs. Solution structures and crystal
      structures of several different FHA domains and their complexes with short
      phosphopeptides have been reported by several groups. We now report the solution
      structure of the FHA domain of human Ki67, a large nuclear protein associated
      with the cell-cycle. Using fragments of its binding partner hNIFK, we show that
      Ki67-hNIFK binding involves ca 44 residues without a pTXX(D/I/L) motif. The pThr
      site of hNIFK recognized by Ki67 FHA is pThr234-Pro235, a motif also recognized
      by the proline isomerase Pin1. Heteronuclear single quantum coherence (HSQC) NMR
      was then used to map out the binding surface, and structural analyses were used
      to identify key binding residues of Ki67 FHA. The results represent the first
      structural characterization of the complex of an FHA domain with a biologically
      relevant target protein fragment. Detailed analyses of the results led us to
      propose that three major factors control the interaction of FHA with its target
      protein: the pT residue, +1 to +3 residues, and an extended binding surface, and
      that variation in the three factors is the likely cause of the great diversity in
      the function and specificity of FHA domains from different sources.

PMID- 14659765
TI  - The functions of the N terminus of the phiX174 internal scaffolding protein, a
      protein encoded in an overlapping reading frame in a two scaffolding protein
      system.
AB  - phiX174 utilizes two scaffolding proteins during morphogenesis, an internal
      protein (B) and an external protein (D). The B protein induces a conformational
      change in coat protein pentamers, enabling them to interact with both spike and
      external scaffolding proteins. While functions of the carboxyl terminus of
      protein B have been defined, the functions of the amino terminus remain obscure.
      To investigate the morphogenetic functions of the amino terminus, several 5'
      deleted genes were constructed and the proteins expressed in vivo. The DeltaNH(2)
      B proteins were assayed for the ability to complement an ochre B mutant and
      defects in the morphogenetic pathway were characterized. The results of the
      biochemical, genetic and second-site genetic analyses indicate that the amino
      terminus induces conformational changes in the viral coat protein and facilitates
      minor spike protein incorporation. Defects in conformational switching can be
      suppressed by substitutions in the external scaffolding protein, suggesting some
      redundancy of function between the two proteins.

PMID- 14659766
TI  - Oxidative stress in heart failure. More than just damage.

PMID- 14659767
TI  - Growth hormone and proinflammatory cytokine activation in heart failure. Just a
      new verse to an old sirens' song?

PMID- 14659768
TI  - The adhesion molecule P-selectin and cardiovascular disease.
AB  - The adhesion molecule P-selectin (CD62P) is of interest because of its role in
      modulating interactions between blood cells and the endothelium, and also because
      of the possible use of the soluble form as a plasma predictor of adverse
      cardiovascular events. Although present on the external cell surface of both
      activated endothelium and activated platelets, it now seems clear that most, if
      not all, of the measured plasma P-selectin is of platelet origin. P-selectin is
      partially responsible for the adhesion of certain leukocytes and platelets to the
      endothelium. Animal models have also shown the important role of P-selectin in
      the process of atherogenesis. For example, increased P-selectin expression has
      been demonstrated on active atherosclerotic plaques; in contrast, fibrotic
      inactive plaques lack P-selectin expression, and animals lacking P-selectin have
      a decreased tendency to form atherosclerotic plaques. Increased levels of soluble
      P-selectin in the plasma have also been demonstrated in a variety of
      cardiovascular disorders, including coronary artery disease, hypertension and
      atrial fibrillation, with some relationship to prognosis. The objective of this
      review is to provide an overview of the current literature on this molecule and
      thus present a concise view of its potential in dissecting the pathophysiology of
      atherosclerosis. In doing so we shall focus primarily on human biology but will
      note a small number of excellent lessons provided by non-human work.

PMID- 14659769
TI  - Correlation of oxidative stress with activity of matrix metalloproteinase in
      patients with coronary artery disease. Possible role for left ventricular
      remodelling.
AB  - AIMS: Oxidative stress is implicated in the progression of heart failure, and
      matrix metalloproteinase (MMP) activity is increased in patients with congestive
      heart failure. We examined the role of oxidative stress on MMP activity in
      humans. METHODS AND RESULTS: We measured the MMP activity and the level of 8-iso
      prostagandin F2alpha (8-iso-PGF2alpha), a specific and quantitative maker of
      oxidant stress, in the pericardial fluid (PF) in 47 consecutive patients with
      coronary artery disease who underwent coronary artery bypass surgery. Zymography
      of PF showed bands at 92-85kDa (MMP-9) and 72-65kDa (MMP-2). The MMP activity was
      expressed as the ratio to MMP-2 standard. MMP-2, MMP-9 and total gelatinolysis
      activities were positively correlated with left ventricular end-diastolic volume
      index (LVEDVI), and MMP-2 and total gelatinolysis activities were also positively
      correlated with LV end-systolic volume index. Moreover, MMP-2, MMP-9 and total
      gelatinolysis activities were all positively correlated with pericardial level of
      8-iso-PGF2alpha. Also, LVDEVI was positively correlated with pericardial level of
      8-iso-PGF2alpha. CONCLUSIONS: Oxidative stress may play an important role in the
      regulation of MMP activity. Augmented MMP activity may be involved in the
      development of ventricular remodelling in patients with coronary artery disease.

PMID- 14659770
TI  - Effects of growth hormone on circulating cytokine network, and left ventricular
      contractile performance and geometry in patients with idiopathic dilated
      cardiomyopathy.
AB  - BACKGROUND: Recent experimental and clinical data indicate that abnormal central
      and peripheral immune reactions contribute to the progression of chronic heart
      failure, and that immunomodulation may be an important therapeutic approach in
      this syndrome. Aims We sought to study the effects of growth hormone (GH)
      administration on circulating pro-inflammatory/anti-inflammatory cytokine
      balance, and to investigate whether these GH-induced immunomodulatory effects are
      associated with the improvement of left ventricular (LV) contractile performance
      in idiopathic dilated cardiomyopathy (DCM) patients. METHODS: Plasma pro
      inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6
      (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and its soluble
      receptor (sGM-CSFR), chemotactic cytokine macrophage chemoattractant protein-1
      (MCP-1), soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1)
      and vascular cell adhesion molecule-1 (sVCAM-1), and, finally, anti-inflammatory
      cytokines interleukin-10 (IL-10) and transforming growth factor-beta2 (TGF-beta2)
      were measured (ELISA method) in 12 patients with DCM (NYHA class III; LV ejection
      fraction: 23.6+/-1.7%) before and after a 3-month subcutaneous administration of
      GH 4IU every other day (randomized crossover design). Peak oxygen uptake (VO2
      max), LV dimensions, LV mass index, end-systolic wall stress (ESWS), mean
      velocity of circumferential fibre shortening (Vcfc), and contractile reserve
      (change of ratio Vcfc/ESWS after dobutamine administration) were also determined
      at the same period. RESULTS: Treatment with GH produced a significant reduction
      in plasma TNF-alpha (7.8+/-1.1 vs 5.5+/-0.9pg/ml, P=0.013), IL-6 (5.7+/-0.5 vs
      4.7+/-0.4pg/ml, P=0.043), GM-CSF (27.3+/-1.7 vs 23.3+/-1.8pg/ml, P=0.042), sGM
      CSFR (4.0+/-0.4 vs 3.2+/-0.4ng/ml, P=0.039), MCP-1 (199+/-5 vs 184+/-6pg/ml,
      P=0.048), sICAM-1 (324+/-34 vs 274+/-27ng/ml, P=0.008) and sVCAM-1 (1238+/-89 vs
      1043+/-77ng/ml, P=0.002) in DCM patients. A significant increase in ratios IL
      10/TNF-alpha (1.9+/-0.3 vs 3.5+/-0.9, P=0.049), IL-10/IL-6(2.6+/-0.6 vs 3.2+/
      0.5, P=0.044) and TGF-beta2/TNF-alpha (3.1+/-0.6 vs 4.4+/-0.6, P=0.05) was
      alsofound with GH therapy. A significant reduction in ESWS (841+/-62 vs 634+/
      48gr/cm(2), P=0.0026) and LV end-systolic volume index (LVESVI, 128+/-12 vs 102+/
      12ml, P=0.035) as well as a significant increase in posterior wall thickness
      (PWTH, 9.2+/-0.5 vs 10.3+/-0.6mm, P=0.034), contractile reserve (0.00029+/-0.0001
      vs 0.00054+/-0.0001circ*cm(2)/gr*s, P=0.00028) and VO2max (15.3+/-0.7 vs 17.1+/
      0.9ml/kg/min, P=0.002) were observed after GH administration. Good correlations
      were found between GH-induced increase in contractile reserve and the increases
      in VO2max (r=0.63, P=0.028), IL-10/TNF-alpha (r=0.69, P=0.011) and TGF-beta2/TNF
      alpha (r=0.58, P=0.046) ratios, as well as the reduction in plasma TNF-alpha
      levels (r=-0.86, P=0.0004). CONCLUSIONS: GH administration modulates beneficially
      circulating cytokine network and soluble adhesion molecules in patients with DCM,
      whilst enhancing contractile reserve and diminishing LV volumes. These GH-induced
      anti-inflammatory effects may be associated with the improvement in LV
      contractile performance and exercise capacity as well as with the reverse of LV
      remodelling of patients with DCM.

PMID- 14659771
TI  - Post menopausal hormone replacement therapy and risk of acute myocardial
      infarction--a case control study of women in the East Midlands, UK.
AB  - AIMS: To examine the relationship between hormone replacement therapy (HRT) and
      acute myocardial infarction (AMI) adjusting for coronary risk factors and social
      and behavioural confounders that might indicate a healthy user effect and could
      account for the discrepancy between randomized and observational studies of HRT
      use. METHODS: A case-control study of 864 women aged between 35-65 suffering an
      AMI with two age matched community controls from the same geographical area.
      Information was collected by interview and from general practitioner records.
      Conditional logistic regression was used to calculate odds ratios (OR) adjusted
      for diabetes, hypertension, smoking, alcohol, social class, family history and a
      health conscious behaviour score. RESULTS: HRT use was recorded for 34% of non
      fatal AMI cases and 39% of controls with the adjusted OR for ever-use of HRT
      versus never-use being 0.74 (95% CI 0.55-0.99). The pattern of risk of AMI was
      similar for oestrogen only and combined HRT. During the first 12 months of HRT
      use there was a small increase in risk of AMI with the adjusted OR being 1.14
      (0.72-1.80). HRT use for 13-60 months was associated with a small reduction in
      AMI risk (adjusted OR 0.85, 0.55-1.29). Only HRT used for >60 months was
      associated with a substantial risk reduction (adjusted OR 0.42, 0.24-0.73). Data
      for deceased cases and controls showed a similar pattern. CONCLUSIONS: HRT use
      whether as oestrogen only or combined hormones was only associated with a
      significant reduction in risk when used for greater than 60 months. These
      findings could reflect a dual effect of HRT on AMI risk by prothrombotic and anti
      atherogenic mechanisms. Neither oestrogen only or combined HRT can be recommended
      for prevention of coronary artery disease.

PMID- 14659772
TI  - Sildenafil citrate does not reduce exercise tolerance in men with erectile
      dysfunction and chronic stable angina.
AB  - AIMS: The aim of this study was to evaluate whether sildenafil, used for
      treatment of erectile dysfunction (ED), affects the exercise tolerance and
      ischaemic threshold in men with exercise-induced angina not taking nitrates.
      METHODS: This was a double-blind placebo-controlled study in men with ED and
      chronic stable angina, assessing the effect of sildenafil on time to limiting
      angina during incremental treadmill exercise. Patients remained on their
      antianginal therapy and received a 100-mg dose of sildenafil or placebo 1h prior
      to treadmill exercise. Other measurements included times to onset of angina, 1-mm
      ST-segment depression, and total exercise time. RESULTS: Adjusted treatment
      differences for the time to limiting angina, time to onset of angina, total
      exercise time, and time to 1-mm ST-segment depression were (mean+/-SE) 20+/-10s
      (95% CI, 1-39; P=0.040), 32+/-11s (95% CI, 11-53; P=0.004), 20+/-10s (95% CI, 0
      39; P=0.049), and 12+/-17s (95% CI, -21 to 45, P=0.48), respectively, in favour
      of sildenafil. There were no serious treatment-related adverse events.
      CONCLUSIONS: Sildenafil was well tolerated and did not adversely affect any
      exercise parameter in men with coronary artery disease and ED. Favourable trends
      in total exercise duration and times to onset of angina and limiting angina were
      recorded with sildenafil use.

PMID- 14659773
TI  - Left ventricular structure and diastolic function with human ageing. Relation to
      habitual exercise and arterial stiffness.
AB  - AIMS: We sought to determine if attenuation of the age-associated increase in
      arterial stiffness by habitual aerobic-endurance exercise would have
      corresponding effects on left ventricular (LV) structure and diastolic function.
      METHODS AND RESULTS: We performed a cross-sectional study on 138 young, middle
      aged, and older men who were either sedentary, recreationally active, or
      endurance exercise-trained. Ageing was associated with increased large artery
      stiffness (aortic pulse wave velocity) and habitual aerobic-endurance exercise
      was associated with decreased large artery stiffness (lower aortic pulse wave
      velocity; all P<0.05). Ageing was associated with increased mean LV wall
      thickness, chamber diameter, mass, concentric remodelling, and a decline in LV
      diastolic function (all P<0.05). Habitual aerobic-endurance exercise was
      independently associated with increased LV wall thickness, chamber diameter, and
      mass (echocardiography; P=0.05 or better). The largest LV mass was seen in older
      endurance trained men, suggesting an additive effect of exercise training and
      ageing on the LV. Indices of LV diastolic function declined with age,
      irrespective of habitual physical activity status. Aortic pulse wave velocity was
      an independent predictor of concentric LV remodelling in the pooled sample, but
      did not predict other properties of LV structure and diastolic function. In
      general, habitual aerobic-endurance exercise status was not uniformly associated
      with favourable modulation of age-associated changes in LV structure and
      diastolic function. CONCLUSIONS: We conclude that in contrast to its ability to
      favourably modulate the stiffness of large elastic arteries, regular aerobic
      endurance exercise does not consistently modulate the changes in LV structure and
      diastolic function that occur with physiological ageing in men.

PMID- 14659774
TI  - Association of lipoproteins with cytokines and cytokine receptors in heart
      failure patients. Differences between ischaemic versus idiopathic cardiomyopathy.
AB  - AIMS: The observation that low total cholesterol predicted poor survival in
      patients with chronic heart failure, has questioned the beneficial effect of
      lipid-lowering in this population. This study investigated the relation between
      lipoprotein concentrations and the levels of interleukin (IL)-6, tumour necrosis
      factor (TNF)-alpha and the soluble TNF-alpha receptors in patients with chronic
      heart failure due to coronary artery disease (CAD) or idiopathic dilated
      cardiomyopathy (IDCM). METHODS AND RESULTS: Seventy-one patients with chronic
      heart failure due to CAD (n=36) or IDCM (n=35) were enrolled. Plasma
      concentrations of lipoproteins, IL-6, TNF-alpha, soluble TNF-alpha receptor 1
      (sTNFR1) and 2 (sTNFR2) were measured. Total cholesterol/HDL-cholesterol
      (CHOL/HDL) correlated with levels of TNF-alpha (r=0.24, P=0.035), sTNFR1 (r=0.32,
      P=0.008) and sTNFR2 (r=0.37, P=0.002). In the CAD group, CHOL/HDL and
      triglycerides (TG) correlated with sTNFR2 (r=0.48, P=0.005 for CHOL/HDL, r=0.40,
      P=0.015 for TG). No relation was found between lipoproteins and cytokines or sTNF
      alpha receptors for IDCM patients (P>0.1). CONCLUSIONS: An atherogenic lipid
      profile favoured the inflammatory process in patients with heart failure due to
      CAD. No relation between lipoproteins and cytokines was detected in case of IDCM.

PMID- 14659775
TI  - Cardiac features of Emery-Dreifuss muscular dystrophy caused by lamin A/C gene
      mutations.
AB  - AIMS: Retrospective studies have identified a mutation in the lamin A/C (LMNA)
      gene in patients selected on the basis of a phenotype characterized by dilated
      cardiomyopathy, atrioventricular conduction disturbances and sudden death.
      However, the features of cardiac abnormalities in patients with an initial
      diagnosis of Emery-Dreifuss muscular dystrophy (EDMD) are poorly known. Aim of
      the present study was to investigate the spectrum of cardiac disease in patients
      with an initial diagnosis of EDMD caused by a mutation in the LMNA gene. METHODS
      AND RESULTS: Ten consecutive patients with EDMD and a LMNA gene mutation were
      evaluated with structured medical interview, physical examination, ECG,
      echocardiogram and 24-h Holter monitoring. Electrophysiological testing and
      cardiac catheterization were performed if a class 1 or 2 American Heart
      Association guidelines indication was present. Cardiac disease was found in eight
      of 10 patients and consisted in the variable combination of supraventricular
      arrhythmias, disorders of atrioventricular conduction, ventricular arrhythmias,
      dilated cardiomyopathy, non-dilated cardiomyopathy, restrictive cardiomyopathy
      and sudden death despite pacemaker implant. CONCLUSIONS: Cardiac disease is
      common in patients with an initial diagnosis of EDMD caused by a mutation in the
      LMNA gene and consists of arrhythmias, disorders of atrioventricular conduction,
      cardiomyopathies and sudden death despite pacemaker implant.

PMID- 14659776
TI  - The relations between the ESC and the European Union. Major initiatives to come
      in health and cardiovascular research.

PMID- 14659777
TI  - Restenosis after coronary stenting: the 'gender paradox'.

PMID- 14659778
TI  - The history of cytogenetics. Portraits of some pioneers.

PMID- 14659779
TI  - FISH and PCR analyses in three patients with 45,X/46,X,idic(Y) karyotype:
      clinical and pathologic spectrum.
AB  - OBJECTIVE: To delineate the phenotypic spectrum (clinical and gonadal features)
      from patients with a 45,X/46,X,mar(Y) karyotype based upon of their clinical,
      histological, cytogenetic and molecular evaluation. SUBJECTS: Three patients with
      a 45,X/46,X,mar(Y) karyotype. METHODS: Clinical assessment, karyotyping,
      endocrine evaluation, FISH and PCR analyses of several Y-chromosome loci and
      direct sequencing of the SRY gene. RESULTS: The patients, two males and one
      female had varying degrees of impairment of sexual differentiation, with or
      without testis formation. One patient (reared as female and aged 17 years) had
      Turner syndrome with bilateral streak gonads. The second patient (2.4 years old)
      had ambiguous genitalia and presented a dysgenetic testis with a contralateral
      streak gonad. A third patient (26 years old) had bilateral dysgenetic testes
      (dysgenetic male pseudohermaphroditism). The ratio of 45,X vs. 46,X,+mar(Y) cells
      differed between patients and between different tissues. In each case the marker
      sexual chromosome was identified as a rearranged Y-chromosome (idic(Y)) using
      FISH and PCR analyses. In all cases the SRY gene was present in all tissues
      studied. No mutations were identified in this gene in any of the patients.
      CONCLUSIONS: The extent of male or female differentiation in these patients
      depends in part on the prevalence, time occurrence, and distribution of the 45,X
      cell line.

PMID- 14659780
TI  - Duane anomaly, congenital myopathy and severe scoliosis in sibs: new AR syndrome?
AB  - We report on two sisters who show a similar pattern of anomalies consisting of
      bilateral Stilling-Turk-Duane retraction syndrome (type 3), non-progressive
      hypotonia with delayed motor milestones but normal intelligence, severe, early
      onset scoliosis, and short stature. Muscular biopsy revealed numerous
      regenerating fibers, but no specific abnormalities among the non-regenerating
      fibers. This combination of anomalies has not been previously reported, and could
      represent a new autosomal recessive syndrome. The only differential diagnosis is
      Crisfield-Dretakis-Sharpe syndrome, a combination of lateral gaze palsy, ptosis,
      and scoliosis without hypotonia, recessively inherited.

PMID- 14659781
TI  - Familial interstitial deletion of chromosome 4 (p15.2p16.1).
AB  - Interstitial deletion of the proximal short arm of chromosome 4, extending from
      p14 to p16.1 region, results in a distinct clinical syndrome. This proximal 4p
      deletion syndrome is characterized by variable degrees of mental retardation,
      unusual facies and minor dysmorphic features. Majority of the patients also show
      a tall, ectomorphic habitus and normal to excessive linear growth with age. While
      there have been several cases of such interstitial del(4p) cases reported,
      familial transmission of this condition has not been documented in the
      literature. This is the first report of a familial transmission of proximal
      del(4p) from a mother to her daughter, with both patients showing similar
      features. This report of the familial transmission of del(4p) has wider
      implications in genetic counseling.

PMID- 14659782
TI  - Limb reduction defects in the first generation and deafness in the second
      generation of intrauterine exposed fetuses to diethylstilbestrol.
AB  - Maternal treatment with diethylstilbestrol (DES) during pregnancy can produce
      vaginal adenocarcinoma and other abnormalities of the vagina in her daughters
      when they reach adolescence or adulthood, miscarriages and absence of full term
      infants. Concerning malformations in newborns whose mothers were treated with
      DES, clitoromegaly and malformations of the uterus were reported in females and
      genital lesions in males. However, the frequencies of major congenital anomalies
      were not greater than expected. We report three cases of limb reduction defects
      (LRD) in the first generation of children whose mothers were treated with DES
      during pregnancy, and two children (one male, one female) with deafness in the
      second generation after intrauterine exposure to DES. The LRD were not associated
      with other congenital anomalies. The malformed children with LRD were born
      between 1965 and 1973. The deafness was also isolated. The two mothers who have
      no hearing problems and who are healthy were exposed in utero to DES in 1963 and
      1965, respectively. Their children were born in 1989 and 1994, respectively. In
      conclusion, the association of LRD and hearing loss with intrauterine exposure to
      DES could be coincidental. However, some hypothesis may explain these
      associations. Congenital hearing loss in the second generation may suggest a
      transgenerational effect.

PMID- 14659783
TI  - Gerstmann-Straussler-Scheinker disease with P102L-V129 mutation: a case with
      psychiatric manifestations at onset.
AB  - Gerstmann-Straussler-Scheinker disease (GSS) is an adult onset, rare, genetically
      determined autosomal dominant prion disease. Clinically, it is characterized
      predominantly by slowly progressive spino-cerebellar dysfunction with ataxia,
      absent reflexes in the legs and cognitive impairment. Onset is usually in the
      fifth decade and in the early phase, ataxia is predominant. Mutations in the
      prion protein gene (PRNP) had been identified and the most important of these is
      at codon 129. A genotype-phenotype relationship with genetic polymorphism at
      residue 129 between methionine and valine has been supposed. We describe a
      patient with GSS and P102L-V129 mutation in which the onset with prominent
      psychiatric features characterized by apathy and depression and not with
      cerebellar sign and the clinical course with seizures, nor observed in P102L-V129
      cases, allow us to confirm observations that the GSS caused by the 102 mutation
      is influenced by the codon 129 polymorphism with a specific genotype-phenotype
      influence, but probably other additional factors might be considered as
      background for phenotypic variability.

PMID- 14659784
TI  - De novo balanced translocation (2;10)(q24;q22) associated with mental
      retardation.
AB  - We report a case of a reciprocal translocation between the long arms of the 2 and
      10 chromosomes observed in a 14-year-old male with mild mental impairment,
      compulsive and obsessive behavior. The apparently balanced translocation was
      characterized by fluorescence in situ hybridization and the karyotype was 46, XY,
      t(2;10)(q24;q22). The way by balanced chromosomal translocations can lead to a
      disease phenotype are reviewed and discussed.

PMID- 14659785
TI  - Paternal reciprocal translocation t(11;16)(p13;q24.3) in a Silver-Russel syndrome
      patient.
AB  - We describe a 7-month-old male child with Silver-Russel syndrome (SRS) phenotype,
      presented with two major clinical features: low birth weight, short stature, and
      minor features, such as macrocephaly, clinodactyly, essential for the diagnosis
      of SRS. Routine cytogenetic studies with GTG-banding showed
      46,XY,t(11;16)(p13;q24.3). Fluorescence in situ hybridisation (FISH) with single
      copy probes BAC (11p13) and PAC (16q24.3), showed a reciprocal translocation.
      Chromosomal analysis of the mother was normal and the phenotypically normal
      father had apparently identical translocation t(11;16)(p13;q24.3). The disruption
      of growth factor genes at 11p and 16q breakpoint regions due to reciprocal
      translocation in the father might have caused SRS phenotype in the child.

PMID- 14659786
TI  - Two 48,XXYY patients: clinical, cytogenetic and molecular aspects.
AB  - Two 48,XXYY males, a young and an adult patient, have been clinically and
      molecularly analysed. Clinical findings seem less severe in the young patient.
      This clinical difference could be mainly due to the age of the younger patient
      or, alternatively, the different pattern of X-inactivation observed in the two
      patients could play a role in the degree of the clinical manifestations.

PMID- 14659787
TI  - "Cri-du-chat" syndrome in a patient born to a mother with a paracentric inversion
      of chromosome 5q.
AB  - We report the case of a female child presented at birth with hypotonia, growth
      retardation and respiratory distress. Chromosome study from peripheral blood
      showed a 46,XX,del(5)(p14pter) karyotype. Parental chromosome studies revealed
      that the mother carried an apparently balanced paracentric inversion of long arms
      of one chromosome 5, giving the karyotype 46,XX,inv(5)(q12q32), whereas paternal
      karyotype was normal. The maternal abnormality was confirmed by fluorescence in
      situ hybridization (FISH) and was not present in the daughter's metaphases.
      Microsatellite analysis in the proposita and her parents permitted us to conclude
      that the deleted chromosome 5 was paternal in origin, as usually described.
      Therefore, as might have been expected, maternal paracentric inversion of
      chromosome 5q and "cri-du-chat syndrome" presented by the daughter were not
      related.

PMID- 14659788
TI  - Shear stress and intermediate-conductance calcium-activated potassium channels.

PMID- 14659789
TI  - Tissue engineering of aortic heart valves.

PMID- 14659790
TI  - Do we understand why regression of left ventricular hypertrophy is beneficial?

PMID- 14659791
TI  - The tantalizing triplet of pulmonary hypertension-BMP receptors, serotonin
      receptors, and angiopoietins.

PMID- 14659792
TI  - Heat stress preconditioning and delayed myocardial protection: what is new?
AB  - As other preconditioning phenomena, heat stress is able to induce a delayed
      myocardial protection against ischaemia-reperfusion injury by preserving
      ventricular function, preventing arrhythmia occurrence and reducing cellular
      necrosis. The development of heat stress response has been extensively studied in
      order to characterize the different steps of this form of preconditioning. It
      appears that chemical signals (such as nitric oxide, reactive oxygen species
      (ROS)) released by sublethal hyperthermic stress trigger a complex cascade of
      signalling events that include activation of protein kinase C (PKC) and mitogen
      activated protein kinases (MAPK) and culminate in increased synthesis of
      inducible nitric oxide synthase, cyclooxygenase-2, antioxidant enzymes and
      protective proteins such as heat stress proteins (Hsps). A better understanding
      of this powerful protective adaptation of the cardiomyocyte is essential for the
      development of clinical applications and the design of cardioprotective
      pharmacological agents. The purpose of this letter is to review current
      information regarding the characteristics of heat stress preconditioning compared
      to other forms of late preconditioning.

PMID- 14659793
TI  - Inhibitory G-proteins and their role in desensitization of the adenylyl cyclase
      pathway in heart failure.
AB  - Heart failure is accompanied by stereotypic alterations in cardiac gene
      expression. These changes are most likely secondary in the pathogenesis and can
      be viewed as protective, e.g. as energy-saving mechanisms, but at the same time,
      they aggravate contractile dysfunction and the deficit of failing cardiac
      myocytes to respond to altered hemodynamic needs. One of the best-studied,
      paradigmatic examples of this dichotomy is heterologous desensitization of the
      cardiac adenylyl cyclase (AC) signaling pathway. It protects against detrimental
      consequences of the excessive adrenergic drive, but it also blunts the most
      powerful inotropic support of the heart. Desensitization is associated with
      downregulation of beta-adrenergic receptors, increased beta-adrenoceptor kinases
      and increased inhibitory G protein alpha-subunits, G(alphai). Whereas a causative
      role of the former is generally accepted, the role of the increase in G(alphai)
      has remained controversial for many years. The present article summarizes early
      and novel findings that, in the view of the authors, provide solid evidence for
      G(alphai) to play an important role in the adaptation of cardiac AC to various
      pathophysiological conditions.

PMID- 14659794
TI  - Shear stress-induced up-regulation of the intermediate-conductance Ca(2+)
      activated K(+) channel in human endothelium.
AB  - OBJECTIVE: Wall shear stress associated with blood flow is a major stimuli for
      generation of endothelial vasodilating and antithrombotic factors and it also
      regulates endothelial gene expression. Activation of endothelial intermediate
      conductance Ca(2+)-activated K(+) channels (IK(Ca)) is important for the control
      of endothelial function by inducing cell hyperpolarization and thus generation of
      the endothelium-derived hyperpolarizing factor. In the present study we tested
      whether the IK(Ca) encoding IKCa1 gene is regulated by laminar shear stress
      (LSS). METHODS: Human umbilical vein endothelial cells (HUVEC) were subjected to
      LSS with a magnitude of 0.5-15 dyn/cm(2) and time intervals of 2-24 h in a flow
      cone apparatus. Expression of the IKCa1 gene and IK(Ca)-functions were determined
      by using real time RT-PCR and patch-clamp techniques. RESULTS: A short 2-4 h-or
      long 24 h-exposure to a LSS with a low (venous) magnitude of 0.5 dyn/cm(2) had no
      effect on IKCa1 expression levels. An exposure for 2 and 4 h to LSS with an
      intermediate magnitude of 5 dyn/cm(2) was also ineffective, whereas an exposure
      for 24 h induced a significant threefold up-regulation of IKCa1 expression
      levels. An exposure to LSS with a higher (arterial) magnitude of 15 dyn/cm(2),
      resulted in an eightfold up-regulation of IKCa1 expression levels after a 4 h
      exposure and a fourfold increase of IKCa1 expression levels at 24 h. The
      increased IKCa1 expression levels following exposure to high levels of LSS
      resulted in enhanced IK(Ca) whole-cell currents and in an increased
      hyperpolarization of the endothelium in response to ATP and the IK(Ca) opener 1
      EBIO. Inhibition of the mitogen-activated protein kinase/extracellular-signal
      regulated kinase (ERK) kinase 1/2 (MEK/ERK) pathway by PD98059 prevented the LSS
      induced up-regulation of IKCa1 expression levels and IK(Ca) whole-cell currents
      indicating that augmentation of IKCa1 expression levels is mediated by the LSS
      induced activation of the MEK/ERK pathway. CONCLUSION: Long term exposure to LSS
      up-regulates expression and function of endothelial IK(Ca). This increase might
      represent a new important mechanism in endothelial adaptation to altered
      hemodynamics.

PMID- 14659795
TI  - Complete dynamic repopulation of decellularized heart valves by application of
      defined physical signals-an in vitro study.
AB  - OBJECTIVE: Cardiovascular tissue engineering is a novel concept to develop ideal
      heart valve substitutes. The objective of this study was to use decellularized
      porcine pulmonary valves, ovine cells and dynamic tissue culture to obtain viable
      and biomechanically stable constructs, resembling native aortic heart valves.
      METHODS: Endothelial cells and myofibroblasts were obtained from ovine carotid
      arteries. Porcine pulmonary valves were decellularized enzymatically, reseeded
      and cultured using a hydrodynamic bioreactor system over a time period of 9 or 16
      days. Controls were grown over an equivalent time period under static conditions.
      Specimens of each valve were examined biochemically (cell proliferation, DNA,
      collagen, 4-hydroxyproline, elastin and glycosaminoglycans), histologically
      (hematoxylin-eosin, Movat-pentachrome and immunostains) and mechanically (radial
      and circumferential strength). RESULTS: Histology and biochemical assays
      demonstrated the removal of almost all cells after decellularization with
      preservation of the extracellular matrix. Recellularization under pulsatile
      conditions was significantly improved after 9 and 16 days compared to static
      conditions. Biochemical and mechanical analysis revealed a continuous increase of
      cell mass, collagen and elastin contents and strength under pulsatile culture
      conditions compared to significantly lower values in the static controls.
      CONCLUSION: This study demonstrated the superiority of the hydrodynamic approach
      of cellular reseeding to replace decellularized porcine heart valves with ovine
      cells with almost complete preservation of extracellular matrix integrity.

PMID- 14659796
TI  - Electrophysiological effects accompanying regression of left ventricular
      hypertrophy.
AB  - OBJECTIVE: The aim of this study was to investigate changes following regression
      of left ventricular hypertrophy (LVH). METHODS: Electrophysiolological changes
      were recorded in isolated guinea-pig myocardial preparations. LVH was induced by
      constriction of the thoracic aorta and regression was followed after removal of
      the constriction. Sham-operated animals served as controls. RESULTS: During 42
      days constriction, heart/body weight ratio increased (3.19+/-0.49 vs. 3.85+/-0.83
      g kg(-1)) and was accompanied by an increase of cell size. Forty-two days after
      clip removal, values had returned to control values. LVH increased action
      potential (AP) duration (mean 112% of control) and decreased conduction velocity
      (60.4+/-3.3 vs. 45.9+/-4.6 cm(-1)). These changes did not return to control after
      regression of LVH. The changes to condition velocity were attributed solely to
      increases of intracellular resistivity. The positive staircase response also
      decreased with LVH, but did recover upon regression. In isolated whole hearts, no
      changes to subepicardial action potential duration, QRS complex duration or AP
      refractory period were observed in LVH or its regression. During low-flow
      ischaemia AP duration shortened reversibly, the rate of shortening was more rapid
      in hypertrophied hearts but similar to control in regressed hearts. The incidence
      of ventricular tachyarrhythmias of fibrillation during low-flow ischaemia was
      similar in control, hypertrophied and regressed hearts. CONCLUSION: Morphological
      regression of LVH is not accompanied by reversal of electrophysiological changes
      measured in isolated preparations, whereas some aspects of contractile function
      to recover.

PMID- 14659797
TI  - Serotonin 5-HT(2B) receptor loss of function mutation in a patient with
      fenfluramine-associated primary pulmonary hypertension.
AB  - OBJECTIVE: Appetite-suppressant drug fenfluramine is implicated in primary
      pulmonary hypertension (PPH) but the molecular pathways that mediate this effect
      are unknown. A mouse model incriminates the serotonin 5-HT(2B) receptor but
      contrasts with other models where this receptor has been shown to mediate
      pulmonary arterial relaxation via nitric oxide production. METHODS: We analyzed
      the human 5-HT(2B) gene in 10 patients with appetite-suppressant drug-associated
      PPH. RESULTS: A mutation causing premature truncation of the protein product was
      found in one patient. The mutation was not found in 80 control subjects and no 5
      HT(2B) mutation was found in 18 PPH patients not associated with appetite
      suppressants. Functional analysis of the transfected receptor expressed either
      transiently in COS cells or stably in CHO cells demonstrated that the mutated
      receptor fails to activate the second messenger inositol-phosphates cascade and
      subsequent intracellular calcium release, in spite of normal expression at the
      cell membrane. The mutated receptor had no constitutive activity, and produced no
      dominant negative effect on the wild-type receptor. CONCLUSION: Loss of serotonin
      5-HT(2B) receptor function may predispose to fenfluramine-associated PPH in man.

PMID- 14659798
TI  - Altered signal transduction in cardiac ventricle overexpressing A(1)-adenosine
      receptors.
AB  - OBJECTIVE: The aim of the present study was to assess the effects of A(1)
      adenosine receptor (A1-AR) stimulation in ventricle of A(1)-adenosine receptor
      overexpressing mice (transgenic mice, TG). METHODS: Effects of the A(1)-adenosine
      receptor agonist R-PIA ((-)-N(6)-phenylisopropyladenosine) on phosphorylation of
      phospholamban (PLB), Ca(2+) transients, Ca(2+) currents and cell shortening were
      studied in isolated ventricular cardiomyocytes. RESULTS: R-PIA alone did not
      affect contractility in isolated electrically stimulated cardiomyocytes from wild
      type mice (WT) or TG. However, after pre-stimulation of beta-adrenoceptors by
      isoproterenol, R-PIA reduced contractility in cardiomyocytes from WT but
      increased contractility in TG. Under the same conditions, R-PIA reduced
      isoproterenol-stimulated currents through L-type Ca(2+) channels, Ca(2+)
      transients and phosphorylation of PLB in cardiomyocytes from WT. In contrast, R
      PIA diminished phospholamban phosphorylation induced by isoproterenol but
      augmented isoproterenol-elevated currents through L-type Ca(2+) channels, and
      isoproterenol-heightened Ca(2+) transients in cardiomyocytes from TG.
      CONCLUSIONS: We suggest that A(1)-adenosine receptor overexpression reverses the
      interaction of beta-adrenergic and A(1)-adenosine receptor stimulation, at least
      in part. Hence, the receptor/effector coupling is dependent on receptor density
      in this model.

PMID- 14659799
TI  - Angiotensin II AT(1)-receptor induces biglycan in neonatal cardiac fibroblasts
      via autocrine release of TGFbeta in vitro.
AB  - OBJECTIVE: After myocardial infarction, angiotensin II (AngII) promotes
      ventricular remodeling and deposition of extracellular matrix (ECM), e.g.,
      collagen type 1 and 3. Whether AngII regulates the expression of small leucine
      rich proteoglycans (SLRP) which are important modulators of collagen
      fibrillogenesis and are induced after experimental myocardial infarction in rats
      is not known. The aim of the present study was therefore to analyse in cultured
      cardiac fibroblasts the expression and secretion of the SLRP biglycan in response
      to AngII. METHODS: Cardiac fibroblasts were isolated from neonatal Wistar Kyoto
      rats and used in the first passage. Expression of AT(1)- and AT(2)-receptors was
      verified by RT-PCR. Expression of protoeglycans was analyzed after metabolic
      labeling with [35S]-sulfate, by SDS-PAGE and Western analysis. In addition, mRNA
      expression was examined by means of RT-PCR and Northern analysis. The activity of
      the biglycan promoter was analyzed using three biglycan promoter-luciferase
      fusion constructs. RESULTS: Biglycan was found to be the predominant proteoglycan
      produced by neonatal cardiac fibroblasts in vitro. In response to AngII (10(-7)
      M), secretion of total [35S]-labeled proteoglycans and mRNA of biglycan were
      increased to 116+/-1.8% and 121+/-11% (n=5, mean+/-S.E.M.) of unstimulated
      controls, respectively. Biglycan induction in response to AngII was sensitive to
      Losartan (10(-5) M) and unaffected by PD123177 (10(-6) M), suggesting that the
      AT(1)-receptor mediates the induction of biglycan. Direct activation of the
      biglycan promoter downstream of the AT(1)-receptor was excluded by promoter
      activity assays. Instead, increased release of transforming growth factor beta 1
      (TGFbeta1) was detected by ELISA in response to AT(1)-receptor stimulation.
      Furthermore, neutralising antibodies to TGFbeta1 inhibited biglycan induction in
      response to AngII. CONCLUSION: The results indicate that in cardiac fibroblasts
      AngII via the AT(1)-receptor causes autocrine release of TGFbeta1, which in turn
      induces biglycan expression and secretion.

PMID- 14659800
TI  - Demonstration of altered fibroblast contractile activity in hypertensive heart
      disease.
AB  - OBJECTIVE: The aim of this study is to investigate the idea that altered
      fibroblast contractile activity is involved in the pathogenesis of hypertensive
      heart disease (HHD). METHODS: Cell area and contraction are quantified using the
      traction force microscopy technique for cardiac fibroblasts isolated from both
      normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats.
      RESULTS: The data indicate that there are marked phenotypic differences between
      the two cell types. For instance, WKY fibroblasts exert an average traction
      stress of approximately 3.3 kPa and have an area of approximately 2640 microm(2).
      Under identical conditions the SHR fibroblasts have an area approximately 1.45
      times larger (p<0.01) and exert an average stress approximately 1.86 times higher
      (p<0.01). Challenging WKY fibroblasts with 1 micromol/l angiotensin II (Ang II)
      gradually causes a approximately 2-fold increase in traction after 1 h while
      simultaneously causing a approximately 28% decrease in area. In contrast, Ang II
      has no effect on SHR fibroblasts. The data also show that WKY and SHR cells
      respond in different ways when challenged with irbesartan (Irb). The addition of
      1 micromol/l Irb initially causes WKY cells to decrease their average traction
      output by approximately 50% after approximately 10 min. Subsequently, contractile
      activity begins to recover and returns to normal after 1 h. The SHR cells also
      decrease their tractions by approximately 50%, but this decrease requires 30 min
      for completion and there is no recovery to the initial contractile state. For
      both cell types, Irb produces no significant effect on area and the combined
      effect of equimolar Irb and Ang II is the same as Irb alone. CONCLUSION: These in
      vitro data suggest that among the many factors producing hypertensive heart
      disease in SHR's are excessive contraction of their cardiac fibroblasts and
      defective control of fibroblast contraction by Ang II.

PMID- 14659801
TI  - Induction of myocardial biglycan in heart failure in rats--an extracellular
      matrix component targeted by AT(1) receptor antagonism.
AB  - OBJECTIVE: Cardiac remodelling associated with congestive heart failure typically
      involves dilatation of the ventricular cavities, cardiomyocyte hypertrophy and
      alterations of extracellular matrix. Biglycan is an extracellular proteoglycan
      with several recently appreciated functions including cell adhesion, collagen
      fibril assembly, and growth factor interactions. The aims of this study were to
      investigate the regulation of biglycan expression and to elucidate the site(s) of
      synthesis of biglycan in myocardial tissue in an experimental model of heart
      failure (HF). METHODS: Myocardial tissue samples were obtained from rats with
      myocardial infarction (MI) subsequent to ligation of the left coronary artery.
      Northern blot analysis and real-time quantitative RT-PCR were employed to
      investigate mRNA levels. The cellular distribution of biglycan was analysed by in
      situ hybridisation and immunohistochemistry. RESULTS: Myocardial biglycan mRNA
      levels in non-ischemic tissue of both left and right ventricles of heart failure
      rats were substantially elevated as compared to sham-operated rats. Although
      expression levels peaked 7 days after MI (13-fold increase compared to the sham
      group, P<0.05), substantial elevations of biglycan mRNA were observed throughout
      the study period. Analysis of cellular distribution revealed that biglycan
      expression was confined to myocardial fibroblasts and vascular endothelial cells.
      In cardiac fibroblasts isolated from failing hearts, biglycan mRNA levels were
      markedly elevated compared with fibroblasts from sham-operated rats. In addition,
      in rats with ischemic heart failure treatment with the AT(1) receptor antagonist
      losartan (12.5 mg.kg(-1) b.i.d. per os, for 25 days) prevented the increase of
      myocardial biglycan as well as TGF-beta(1) mRNA. CONCLUSION: This report
      demonstrates global induction of myocardial biglycan mRNA in heart failure.
      Myocardial biglycan expression could be targeted by AT(1) receptor antagonism, an
      intervention well documented to halt cardiac remodelling in heart failure.
      Furthermore, the study provides evidence that angiotensin II is a regulator of
      biglycan expression in cardiac fibroblasts.

PMID- 14659802
TI  - Cardia bifida, defective heart development and abnormal neural crest migration in
      embryos lacking hypoxia-inducible factor-1alpha.
AB  - OBJECTIVES: Previous studies have revealed the essential role of hypoxia
      inducible factor-1alpha (HIF-1alpha), a basic helix-loop-helix transcription
      factor, in cardiovascular development. We attempted to further characterize the
      underlying mechanisms resulting in abnormal cardiogenesis and defective
      angiogenesis in mice deficient for HIF-1alpha (HIF-1alpha(-/-)). METHODS: We
      analyzed cardiovascular development in HIF-1alpha(-/-) embryos at both the
      macroscopic and microscopic level. Gene expression was determined by RT-PCR, in
      situ hybridization and immunohistochemistry. Embryonic survival was studied using
      whole embryo culture. RESULTS: HIF-1alpha deficiency caused cardia bifida in some
      embryos, while cardiac looping was disturbed in others. These defects did not
      result from abnormal cardiomyocyte commitment or differentiation, but may relate
      to defective ventricle formation caused by reduced expression of myocyte enhancer
      factor 2C (MEF2C) and eHAND. In addition, remodeling of the aortic outflow tract
      and cephalic blood vessels was abnormal in HIF-1alpha(-/-) embryos. These
      malformations, together with the hypoplastic pharyngeal arches, are presumably
      induced by defective neural crest cell (NCC) migration. Impaired migration might
      be related to insufficient levels of semaphorin-3A (Sema3A). Hyperoxia prolonged
      survival but only partially rescued the developmental program of cultured HIF
      1alpha(-/-) embryos. CONCLUSION: HIF-1alpha is essential for proper cardiac
      development by modulating both neural crest migration and ventricle formation.

PMID- 14659803
TI  - Myosin light chain isoforms modify force-generating ability of cardiac myosin by
      changing the kinetics of actin-myosin interaction.
AB  - OBJECTIVE: To investigate the functional role of myosin light chain (MLC)
      isoforms in cardiac muscles, we examined the motor function of two different
      myosins the structure of which differed only in the MLC. METHODS: We purified
      myosin from atria (A-myosin) and ventricles (V-myosin) of young rats, which
      contained atrial-type and ventricular-type MLCs, respectively, but having
      identical alpha-heavy chain isoform. Actin filament velocity (Vel) was determined
      in the in vitro motility assay. Average force of myosin molecules (F) was
      estimated and single events of actin-myosin interaction were recorded with the
      laser trap technique. RESULTS: Vel was slightly higher in A-myosin than in V
      myosin, while actin-activated ATPase activity was not different. F, determined
      from force versus actin filament length relation, was approximately 60% higher in
      V-myosin (3.3 vs. 2.1 pN/microm). The mean duration of isometric force events was
      longer in V-myosin than in A-myosin (323+/-13 vs. 294+/-30 ms, p<0.05), while the
      amplitudes of unitary displacement and force of a single myosin molecule did not
      differ between them. CONCLUSION: The MLC isoform can be a determinant of force
      generating ability of cardiac myosin by modulating crossbridge kinetics without
      affecting the catalytic activity.

PMID- 14659804
TI  - A low dose of angiotensin II increases inotropism through activation of reverse
      Na(+)/Ca(2+) exchange by endothelin release.
AB  - OBJECTIVE: This work was aimed to prove that release/formation of endogenous
      endothelin acting in an autocrine/paracrine fashion contributes to the increase
      in contractility promoted by a low dose of angiotensin II. METHODS: Isolated cat
      papillary muscles were used for force, pH(i), [Na(+)](i) and [Ca(2+)](i)
      measurements and isolated cat myocytes for patch-clamp experiments. RESULTS: In
      papillary muscles, 1.0 nmol/l angiotensin II increased force by 23+/-2% (n=4,
      P<0.05), [Na(+)](i) by 2.2+/-0.2 mmol/l (n=4, P<0.05), and peak (but not
      diastolic) Ca(2+) from 0.674+/-0.11 to 0.768+/-0.13 micromol/l (n=4, P<0.05),
      without affecting pH(i). Force and [Na(+)](i) increase were abolished by
      inhibition of the Na(+)/H(+) exchanger (NHE) with the inhibitor HOE642, blockade
      of endothelin receptors with the nonselective antagonist TAK044 and by inhibition
      of the endothelin-converting enzyme with phosphoramidon. Force but not [Na(+)](i)
      increase was abolished by inhibition of reverse Na(+)/Ca(2+) exchange (NCX) with
      the inhibitor KB-R7943. Similar increase in force (21+/-2%, n=4, P<0.05) and in
      [Na(+)](i) (2.4+/-0.4 mmol/l, n=4, P<0.05) that were also suppressed by TAK044
      and HOE642 were induced by exogenous 5.0 nmol/l endothelin-1. KB-R7943 reverted
      the endothelin-1 effect on force but not on [Na(+)](i). In isolated myocytes,
      exogenous endothelin-1 dose-dependently increased the NCX current and shifted the
      NCX reversal potential (E(NCX)) to a more negative value (DeltaE(NCX): -10+/-3
      and -17+/-5 mV, with 1 and 10 nmol/l endothelin-1, respectively, n=12). The
      latter effect was prevented by HOE642. CONCLUSION: Taken together, the results
      indicate that a low dose of angiotensin II induces release of endothelin, which,
      in autocrine/paracrine fashion activates the Na(+)/H(+) exchanger, increases
      [Na(+)](i) and changes E(NCX), promoting the influx of Ca(2+) that leads to a
      positive inotropic effect (PIE).

PMID- 14659805
TI  - The alpha(1B)-adrenergic receptor decreases the inotropic response in the mouse
      Langendorff heart model.
AB  - OBJECTIVE: alpha(1)-Adrenergic receptors (ARs) are known mediators of a positive
      inotropy in the heart, which may play even more important roles in heart disease.
      Due to a lack of sufficiently selective ligands, the contribution of each of the
      three alpha(1)-AR subtypes (alpha(1A), alpha(1B) and alpha(1D)) to cardiac
      function is not clearly defined. In this study, we used a systemically expressing
      mouse model that overexpresses the alpha(1B)-AR to define the role of this
      subtype in cardiac function. METHODS: We used the mouse Langendorff heart model
      to assess changes in contractility under basal and phenylephrine-induced
      conditions. RESULTS: We find that a 50% increase of the alpha(1B)-AR in the heart
      does not change basal cardiac parameters compared to age-matched normals (heart
      rate, +/-dP/dT and coronary flow). However, the inotropic response to
      phenylephrine is blunted. The same results were obtained in isolated adult
      myocytes. The difference in inotropy could be blocked by the selective alpha(1A)
      AR antagonist, 5-methylurapidil, which correlated with decreases in alpha(1A)-AR
      density, suggesting that the alpha(1B)-AR had caused a compensatory
      downregulation of the alpha(1A)-AR. CONCLUSIONS: These results suggest that the
      alpha(1B)-AR does not have a major role in the positive inotropic response in the
      mouse myocardium but may negatively modulate the response of the alpha(1A)-AR.

PMID- 14659806
TI  - Release of TNF-alpha during myocardial reperfusion depends on oxidative stress
      and is prevented by mast cell stabilizers.
AB  - OBJECTIVES: Our study sought to elucidate the role of oxidative stress for
      shedding of tumor necrosis factor-alpha (TNF-alpha) and for activating TNF-alpha
      converting enzyme (TACE). BACKGROUND: TNF-alpha, a central inflammatory cytokine,
      is discussed as one of the mediators of reperfusion injury. Shedding of membrane
      bound pro-TNF-alpha is thought to be largely due to TNF-alpha-converting enzyme
      (TACE). METHODS: Release of TNF-alpha and TACE dependency were studied in
      isolated rat hearts and in the human mast cell line HMC-1. RESULTS: In reperfused
      hearts, interstitial release of TNF-alpha occurred in two phases (2-10 and >45
      min). It depended on the presence of oxygen during reperfusion and was attenuated
      by reduced glutathione. Infusion of the oxidants H(2)O(2) or HOCl elicited
      release in non-ischemic hearts. TNF-alpha release was inhibited in hearts treated
      with degranulation inhibitors ketotifen or cromoglycate, suggesting mast cells as
      major source for myocardial TNF-alpha. This was confirmed by tissue staining.
      Post-ischemic release of histamine, however, did not parallel that of TNF-alpha.
      Heart tissue contained mainly mature TACE. HMC-1 expressed abundant pro-TACE and
      cleaved the pro-TNF-alpha-peptide Ac-SPLAQAVRSSSR-NH(2). However, cleavage was
      nonspecific and only partly inhibited by TACE inhibitor TAPI-2 (10-100
      micromol/l), while it was stimulated by H(2)O(2) and HOCl and fully blocked by
      the nonspecific metalloprotease inhibitor o-phenanthroline. CONCLUSIONS: The
      mechanism underlying TNF-alpha release from post-ischemic myocardium is oxidation
      dependent but largely independent of activation of TACE. Mast cell stabilizers
      may be useful in preventing TNF-alpha release during reperfusion.

PMID- 14659807
TI  - Inhibiting mitochondrial permeability transition pore opening at reperfusion
      protects against ischaemia-reperfusion injury.
AB  - OBJECTIVE: The opening of the mitochondrial permeability transition pore (mPTP)
      in the first few minutes of post-ischaemic reperfusion is a critical determinant
      of reperfusion-induced cell death. We hypothesised that the novel
      immunosuppressant, sanglifehrin-A (SFA), given at the time of reperfusion,
      protects the myocardium from ischaemia-reperfusion injury, by suppressing mPTP
      opening. METHODS: Isolated perfused rat hearts were subjected to 35 min
      ischaemia/120 min reperfusion, and were treated with (1) SFA (1.0 microM) or (2)
      DMSO vehicle for the first 15 min of reperfusion or (3) SFA (1.0 microM) after
      the first 15 min of reperfusion. We examined the effect of SFA on mPTP opening
      directly, using a myocyte model of oxidative stress. Laser illumination of adult
      rat myocytes loaded with the fluorophore, TMRM, generates oxidative stress, which
      induces mPTP opening (represented by mitochondrial membrane depolarisation)
      followed by rigour contracture. RESULTS: In the isolated perfused heart model,
      SFA, given during the first 15 min of post-ischaemic reperfusion, reduced the
      infarct-risk volume ratio from 43.9+/-2.5% in the control group to 23.8+/-4.2%
      with SFA (p=0.001). However, when SFA was given after the first 15 min of
      reperfusion, there was no change in infarct size (43.8+/-5.7% with SFA vs. 43.9+/
      2.5% in control; p=NS), suggesting that SFA has to be present during the first 15
      min of reperfusion to induce protection. In the isolated adult myocyte model, SFA
      was shown to inhibit mPTP opening in the setting of oxidative stress, represented
      by an increase in the ROS threshold required to induce: mitochondrial membrane
      depolarisation (from 269+/-21 to 777+/-100 s; p<0.001) and rigour contracture
      (from 613+/-14 to 1329+/-129 s; p<0.001). CONCLUSIONS: Inhibiting mPTP opening
      during the first few minutes of reperfusion, using sanglifehrin-A, limits infarct
      size and protects myocytes from oxidative stress.

PMID- 14659808
TI  - Modulation of endothelial Ca(2+)-activated K(+) channels by oxidized LDL and its
      contribution to endothelial proliferation.
AB  - OBJECTIVE: Oxidized low-density lipoprotein (oxLDL) plays an important role in
      causing endothelial dysfunction and initiating atherosclerosis. Some of the
      endothelial functions have been shown to be modulated by changes in cellular
      electrophysiological properties. Therefore, we analysed the effect of oxLDL on
      endothelial Ca(2+)-activated K(+) channels (BK(Ca)) and its contribution to oxLDL
      mediated changes of proliferation and syntheses of nitric oxide (NO). METHODS:
      The patch-clamp technique was used to study the behavior of BK(Ca) in human
      endothelial cells of umbilical cord veins (HUVEC). Changes of intracellular
      Ca(2+) were measured by means of Fura-2 imaging. Cell counts and [3H]-thymidine
      incorporation were used to analyse endothelial proliferation. Synthesis of NO was
      measured by means of [3H]-cGMP radioimmunoassay. RESULTS: oxLDL (10 microg/ml)
      caused a significant increase of BK(Ca) activity, whereas preincubation of HUVEC
      with an antibody against the lectin-like-oxLDL-receptor-1 (LOX-1) abolished
      BK(Ca) activation. Fura-2 measurements revealed a biphasic increase of
      intracellular Ca(2+) after application of the atherogenic lipid. Endothelial
      proliferation was significantly increased by oxLDL. The highly selective BK(Ca)
      inhibitor iberiotoxin (100 nmol/l IBX) blocked this proliferative response.
      Acetylcholine-induced NO synthesis was significantly decreased by IBX.
      Interestingly, oxLDL significantly decreased acetylcholine-induced NO synthesis
      if the production of superoxide was not blocked by antisense oligonucleotides
      against the NAD(P)H-oxidase. CONCLUSIONS: Our data demonstrate that oxLDL
      activates BK(Ca), which plays an important role in oxLDL-mediated endothelial
      proliferation. Acetylcholine-induced NO synthesis is modulated by BK(Ca), whereas
      the reduction of acetylcholine-induced NO-synthesis by oxLDL is related to an
      increase in superoxide production.

PMID- 14659809
TI  - Endothelial-dependent vasodilation is reduced in mesenteric arteries from
      superoxide dismutase knockout mice.
AB  - OBJECTIVE: Oxidative stress has increasingly been implicated in the development
      and progression of many vascular diseases. Previous work from our laboratory
      indicated that peroxynitrite alters vasoactive pathways in endothelial cells,
      which could potentially reduce vascular relaxation. To test this hypothesis in
      vivo, we utilized an animal model of endogenous oxidative stress, the CuZn
      superoxide dismutase (SOD) knockout mouse, to assess vascular function. METHODS:
      Vascular reactivity of mouse mesenteric arteries was assessed in the presence or
      absence of inhibitors to nitric oxide synthase (NOS) and/or prostaglandin H
      synthase (PGHS). Endothelial-dependent function was also measured after the
      addition of exogenous SOD. Peroxynitrite formation was detected by nitrotyrosine
      immunofluorescence in mesenteric arteries. RESULTS: Our data indicate that
      endothelial-dependent relaxation responses to methacholine are highly reduced in
      SOD-/- mice (P<0.01, ANOVA). In only the wild-type mice, NOS or PGHS inhibition
      significantly blunted relaxation, suggesting that vasodilators from these
      pathways are present only in the controls and not in SOD-/- mice. A combination
      of NOS and PGHS inhibitors reduced methacholine relaxation in both wild type and
      SOD-/- mice. This residual EDHF-like relaxation was not different between groups.
      After incubation with exogenous SOD, endothelial-dependent relaxation could be
      partially restored in SOD-/- mice, due to increased NOS-mediated vasodilation. In
      addition, peroxynitrite formation was significantly elevated in mesenteric
      arteries from SOD-/- mice. CONCLUSION: Our data suggest that in a novel animal
      model of oxidative stress, vessel function is compromised due to alterations in
      NOS and PGHS-dependent relaxation responses.

PMID- 14659810
TI  - Expression of homocellular and heterocellular gap junctions in hamster arterioles
      and feed arteries.
AB  - OBJECTIVES: Conduction of vasoconstrictor and vasodilator responses in the
      microcirculation involves electrical coupling through gap junction channels among
      cells of the vascular wall. The present study determined whether reported
      differences in the properties of conduction along the arterioles of the
      epithelial hamster cheek pouch (CPA) and feed arteries of its retractor skeletal
      muscle (RFA) result from differences in the expression profile of specific
      connexin (Cx) isoforms and the gap junctions they comprise. METHODS: Real-time
      PCR, immunohistochemistry and serial section electron microscopy were used to
      compare wall morphology and the distribution of gap junctions between respective
      vessels. RESULTS: Expression of mRNA for Cx37, 40, 43 and 45 was similar between
      CPA and RFA. In the endothelium, Cx37, 40 and 43 proteins were expressed
      abundantly between adjacent cells while Cx37 was present in the smooth muscle. In
      both vessels, endothelial and smooth muscle cell (SMC) layers were well connected
      by myoendothelial gap junctions (MEGJs), which were found near endothelial cell
      (EC) gap junctions. CONCLUSIONS: The absence of differential gap junctional
      expression between CPA and RFA, in spite of documented differences in cellular
      conduction pathways, supports the hypothesis that conductance of vascular gap
      junction channels can be differentially modulated in resistance microvessels.

PMID- 14659811
TI  - Stenosis progression after surgical injury in Milan hypertensive rat carotid
      arteries.
AB  - BACKGROUND: Milan hypertensive rats (MHS) are characterised by an increase in
      renal sodium reabsorption mainly related to adducin mutations. Interest in this
      model relies on the genetic link between adducin polymorphisms and primary
      hypertension, observed also in a subset of patients. OBJECTIVES: To investigate
      the molecular and morphological events involved in carotid stenosis and triggered
      by surgery in MHS model. METHODS: Stenosis was induced through arteriotomy. At
      different times after injury, the expression profiles of various gene families
      were investigated by semi-quantitative reverse transcription-polymerase chain
      reaction (RT-PCR), while histological techniques were used to follow morphometric
      and morphological changes. Apoptotic nuclei were revealed by terminal
      deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL). RESULTS: mRNAs
      coding for transcription factors c-jun, c-fos and c-myc were rapidly induced by
      injury. Analysis of apoptosis-related genes revealed a decrease of the Bcl-2/Bax
      ratio 4 h after vascular trauma (P<0.05), followed by a recovery of antiapoptotic
      factors 24 and 48 h later. ET(A) and receptor mRNAs decreased after the injury
      and were replaced by ET(B) and AT2 mRNAs. Both ET(A) and AT1 turned to basal
      level 48 h after injury. Expression profiles of chatepsins B and D were also
      determined. A marked neoadventitia led to maximal 60+/-9% lumen reduction
      (P<0.05) 30 days after surgery. Media substitution by fibrotic and granulomatous
      tissue was also evident. Maximal 47+/-2% apoptotic nuclei were detected 48 h
      after the injury (P<0.05). CONCLUSIONS: The injury applied to MHS carotids
      induces negative remodelling and a limited apoptotic reaction. These findings
      could arise from the balancing among proliferative factors, apoptosis-related
      molecules and relaxant anti-proliferative receptors, all stimulated by the
      injury.

PMID- 14659812
TI  - Effect of adventitial VEGF(165) gene transfer on vascular thickening after
      coronary artery balloon injury.
AB  - OBJECTIVE: Experimental studies have provided evidence that neovascularization is
      an important feature of plaque growth, and angiogenic gene therapy may,
      therefore, increase plaque growth. This study examined the effect of local
      (peri)adventitial vascular endothelial growth factor165 (VEGF) gene transfer on
      vascular thickening after coronary balloon injury. METHODS: Two coronary arteries
      of 15 pigs were subjected to balloon injury followed by either (peri)adventitial
      VEGF165 or beta-galactosidase (LacZ) plasmid/liposome-mediated gene transfer via
      needle injection catheter. At days 3, 14 and 28, histologic sections of coronary
      arteries were analyzed. RESULTS: Transferred VEGF165 gene and increased
      adventitial neovascularization were detected in coronary arteries after balloon
      injury and VEGF injection. The mean intima+media (I+M) area increased after
      coronary balloon injury and VEGF (1.13+/-0.17 and 2.54+/-0.52 mm(2)) or LacZ
      (1.37+/-0.19 and 2.96+/-0.41 mm(2)) gene transfer, with no significant difference
      between both groups at 3 and 28 days, respectively. No significant difference in
      I+M neovascularization was observed at day 28 between the treatment groups
      (microvessel area density 0.24+/-0.08% with VEGF and 0.26+/-0.14% with LacZ,
      respectively). I+M endothelial cell proliferation index ranged from 7% to 22%
      (VEGF) and 18% to 24% (LacZ). CONCLUSIONS: Catheter-mediated (peri)adventitial
      VEGF165 gene transfer induces adventitial neovascularization but not an increase
      of vascular thickening/I+M growth and vascularization in a porcine model of
      coronary artery injury.

PMID- 14659813
TI  - Differential cyclin E expression in human in-stent stenosis smooth muscle cells
      identifies targets for selective anti-restenosis therapy.
AB  - OBJECTIVE: Cell cycle inhibitors are promising agents to prevent or treat human
      coronary in-stent stenosis (ISS). However, their lack of specificity for ISS
      vascular smooth muscle cells (VSMCs) may inhibit medial VSMC proliferation and
      suppress vessel healing. METHODS: To identify inhibitor targets that
      differentially regulate proliferation of ISS vs. medial VSMCs, we examined cell
      cycle regulation in human VSMCs derived from (A) normal media, (B) ISS sites and
      (C) primary atherosclerotic plaques (P-VSMCs) using time-lapse videomicroscopy,
      flow cytometry, immunoblotting and immunohistochemistry. RESULTS: ISS-VSMC
      proliferation was intermediate between P-VSMCs and medial VSMCs. Compared with
      medial cells, P-VSMCs expressed increased p16 and p21, reduced p27, reduced
      cyclins D(1) and E, and reduced pRb phosphorylation. In contrast, ISS-VSMCs
      expressed high levels of cyclins E and A with pRb hyperphosphorylation, both in
      vitro and in vivo, associated with increased and chronic cell proliferation in
      vivo. Roscovitine, a selective CDK2 inhibitor, inhibited VSMC proliferation by
      both pRb-dependent and independent pathways and more potently in ISS-VSMCs than
      medial VSMCs. CONCLUSIONS: Human ISS-VSMCs have marked differences in the stable
      expression of multiple cell cycle regulators, suggesting that ISS-VSMCs derive
      from P-VSMCs driven to proliferate through cyclin E overexpression. The critical
      role for cyclin E-CDK2 enables the identification of the first agent that
      selectively inhibits ISS-VSMC proliferation.

PMID- 14659814
TI  - Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at
      the time of clinical in-stent restenosis.
AB  - OBJECTIVE: Intralesional data of coronary target lesions following stent
      implantation are infrequent. In addition, there is ongoing controversy on the
      origin of neointimal cells. In this respect, several lines of evidence revealed
      bone-marrow-derived endothelial progenitor and dendritic cells (DCs) as well as
      neural-crest-derived cells (NCCs) to contribute to atherosclerosis. Therefore,
      the objective of the present study was to assess cellularity, cell type and
      origin of neointimal cells in in-stent restenosis (ISR). METHODS: Atherectomy
      specimens from 17 patients with coronary in-stent restenosis (n=10; time post
      stenting 5+/-3 months) and with peripheral in-stent restenosis (n=7; 7+/-3
      months) versus those from 10 patients with primary lesions were
      immunohistochemically examined for the presence of the determinants CD34, AC133,
      S100, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE),
      nerve growth factor receptor (NGFR) and alpha-smooth muscle actin followed by
      computer-assisted morphometry. RESULTS: In-stent restenosis probes consistently
      demonstrated homogeneous hypercellularity (942+/-318 cells/mm(2)) compared to de
      novo lesions (347+/-120 cells/mm(2), P<0.001). alpha-smooth muscle actin positive
      cells occupied 67% of intimal cells in in-stent restenosis. As a key finding,
      expression of endothelial progenitor cells (CD34: 7.1+/-2.5% positive/total cells
      vs. 0.6+/-0.7%, P<0.001; AC133: 7.0+/-3.4% vs. 1.0+/-0.7%, P<0.001), dendritic
      cells (S100: 9.8+/-5.6% vs. 1.4+/-1.1%, P<0.001) and neural-crest-derived cells
      (GFAP: 7.9+/-2.4% vs. 3.1+/-1.0%; NSE: 4.4+/-2.6% vs. 1.3+/-1.6%; NGFR: 4.2+/
      2.5% vs. 1.1+/-0.7%; each P<0.001) was significantly increased in in-stent
      restenosis compared to primary lesions. CONCLUSIONS: Bone-marrow- and neural
      crest-derived cells, the most dendritic cells, are consistently present in in
      stent restenosis, whereas alpha-smooth muscle actin positive cells constitute the
      largest intimal cell pool. Our data suggest the recruitment of primarily
      extravascular cells within neointima formation in human in-stent restenosis.

PMID- 14659815
TI  - Serotonin receptor antagonist inhibits monocrotaline-induced pulmonary
      hypertension and prolongs survival in rats.
AB  - OBJECTIVES: It has been reported that serotonin (5-HT) is involved in the
      development of pulmonary arterial hypertension (PAH) with pulmonary vascular
      remodeling. The purpose of the present study was to examine the role of a 5-HT2A
      receptor antagonist, sarpogrelate hydrochroride, in preventing or reversing
      monocrotaline (MCT)-induced PAH in rats. METHODS: Rats were injected with 40
      mg/kg of MCT subcutaneously and randomized to either sarpogrelate (50 mg/kg,
      intraperitoneally) or placebo for 3 weeks. Animals treated with MCT and survived
      for 3 weeks were assigned to either sarpogrelate (50 mg/kg, intraperitoneally) or
      placebo for next 3 weeks. The animals had pressure measurement of the pulmonary
      artery, and then underwent histologic, immunohistochemical, and Western blot
      analyses of the lung tissue. Survival rate was also assessed after treatment.
      RESULTS: Sarpogrelate immediately following MCT injection suppressed PAH with
      severe pulmonary vascular remodeling and right-sided heart failure. The survival
      rate was significantly increased in the sarpogrelate-treated group compared with
      the placebo group (71% vs. 44%, p<0.05). Intense expression of P-selectin was
      found on the endothelium of the pulmonary arteries in the placebo group, and it
      was markedly attenuated in the sarpogrelate-treated group. The numbers of the
      CD45-positive cells and those of the proliferating cell nuclear antigen (PCNA)
      positive cells in the lung tissue were significantly increased in the placebo
      group, and the increases in these cells were prevented by sarpogrelate.
      Endothelial nitric oxide synthase (eNOS) expression in the lung tissue was
      markedly decreased in the placebo group, but it was prevented by sarpogrelate
      (p<0.001). In contrast, late treatment with sarpogrelate failed to reverse
      established PAH. CONCLUSIONS: Specific 5-HT2A receptor blockade with sarpogrelate
      immediately after MCT inhibited PAH and prolongs survival in rats. These effects
      were accompanied by anti-inflammatory and anti-proliferative effects in the lung
      tissue and marked improvement of pulmonary vascular endothelial dysfunction and
      activation.

PMID- 14659816
TI  - Sildenafil-induced cardioprotection in rabbits.

PMID- 14659818
TI  - Optimization of Golgi methods for impregnation of brain tissue from humans and
      monkeys.
AB  - Golgi impregnation is unique in its ability to display the dendritic trees of
      large numbers of individual neurons. However, its reputation for inconsistency
      leaves many investigators reluctant to embrace this methodology, particularly for
      the study of formalin-fixed human brain tissue. After reviewing the literature,
      testing a variety of technical variations, and discussing the procedure with
      experienced practitioners, we have concluded that much of the unpredictability
      can be removed by matching the Golgi technique to the conditions that were used
      for fixation of the tissue. Briefly fixed tissues worked best with the rapid
      Golgi technique, which includes osmium during the initial chromation step, and
      with the Golgi-Cox method, which includes mercuric chloride during chromation.
      For tissues that have been fixed for several years or even for several decades,
      superior results are obtained with the Golgi-Kopsch technique, using multiple
      changes of a chromation solution that contains paraformaldehyde. In the Golgi
      Kopsch technique, pH should be used to monitor the reduction of Cr6+ to Cr3+,
      which is a crucial determinant of successful chromation. With any Golgi
      technique, agitation throughout the impregnation helps to avoid precipitates and
      to improve the quality of impregnation. When the appropriate method is chosen,
      Golgi impregnation is a useful technique for the neuropathologist.

PMID- 14659819
TI  - Fabrication and characteristics of an implantable, polymer-based, intrafascicular
      electrode.
AB  - We describe new manufacturing techniques and physical properties of an improved
      polymer-based longitudinal intrafascicular electrode (polyLIFE). Modifications
      were made to correct: (1) poor metal film adhesion and fatigue resistance, (2)
      inconsistent insulation adhesion and control over recording/stimulation zone
      length, and (3) insufficient tensile strength for clinical use. Metal adhesion
      was significantly improved by both plasma treatment and fiber rotation (about the
      long axis) during metal deposition. Fatigue resistance was improved by reduction
      in sputtering energy (time x power) combined with long axis rotation, resulting
      in thin metal films that were 250 times more resistant to cyclic bending fatigue.
      Insulation adhesion was enhanced with the application of an adhesion-promoting
      silicone (MED2-4013, Nusil), while the recording/stimulation zone length was
      controlled to 1 +/- 0.2mm (mean +/- S.D.). The polyLIFE was made more robust by
      the inclusion of three individually metallized fibers, improving its tensile
      strength by a factor of 4 while producing minimal changes to its overall
      stiffness. However, the metallized fiber redundancy did not significantly affect
      fatigue resistance. The manufacturing changes described in this study enable the
      construction of more mechanically robust polyLIFEs, which should provide greater
      success when chronically implanted in peripheral nerves.

PMID- 14659820
TI  - Binding of cocaine-like radioligands to the dopamine transporter at 37 degrees C:
      effect of Na+ and substrates.
AB  - Although dopamine (DA) translocation by the DA transporter (DAT) requires Na+, a
      role for Na+ in the DA recognition step in the translocation cycle has been
      questioned. Thus, when binding techniques were used to indirectly measure the
      affinity of DA for DAT via its potency in inhibiting cocaine analog binding, no
      stimulation of DA binding was observed when assay temperature was at or below
      room temperature. The present work describes the use of 3H-labeled cocaine
      analogs for assays at 37 degrees C. When there is sufficient Na+ in the medium (>
      or =25 mM), [3H]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([3H]CIT) is an
      excellent radioligand to label human DAT with high affinity in membrane
      preparations of HEK-293 cells expressing the transporter. However, at 0 and 5 mM
      of Na+, appreciable binding of [3H]CIT occurs to proteins other than DAT,
      hampering accurate assessment of DAT-associated binding. No such problems occur
      with the binding of the 4-fluoro homolog of [3H]CIT, [3H]CFT at 37 degrees C, and
      this radioligand can be used at low [Na+], provided enough protein is present in
      the assay. The application of these assays show that, in contrast to the strong
      Na+ dependency of the binding of CFT, the substrates DA, D-amphetamine, p
      tyramine, and DL-octopamine are not stimulated by Na+. This demonstrates that
      lack of Na+ stimulation of binding of substrates, including DA to DAT, in
      membrane preparations at room temperature is not caused by the reduced fluidity
      of the frozen state of the hydrocarbon membrane interior at this temperature as
      compared with the liquid-expanded state at 37 degrees C.

PMID- 14659821
TI  - Microneurography in anesthetized rats for the measurement of sympathetic nerve
      activity in the sciatic nerve.
AB  - Microneurography is widely used for the measurement of human peripheral
      sympathetic nerve activity (SNA) in conscious subjects by virtue of its low
      invasive nature, but has rarely been employed in animal experiments. Because the
      low invasive nature sometimes is very useful even in animal experiments, we
      tested its feasibility for the measurement of SNA in the sciatic nerve of the
      anesthetized rat, aiming in particular to establish a methodology for
      measurement. A tungsten microelectrode was inserted into the nerve exposed at the
      thigh level to detect the "spontaneous, intermittent burst" signal that is one of
      the main characteristics of compound SNA. Such signals were found in more than
      70% of experiments after surgical operators became accustomed to the method.
      Whenever such signals were detected, electrical stimulation of the sympathetic
      chain resulted in induced action potentials detected with the microelectrode
      after a reasonable conduction period. The spikes were successfully reduced after
      administration of hexamethonium bromide, a sympathetic ganglion blocker. On the
      other hand, induced spikes were never observed when we failed to find the
      "spontaneous, intermittent burst" signal. The results demonstrate the feasibility
      of microneurography in evaluating SNA in anesthetized small animals, and that the
      "spontaneous, intermittent burst" signal may be sufficient to identify SNA.

PMID- 14659822
TI  - Separating neural processes using mixed event-related and epoch-based fMRI
      paradigms.
AB  - Mixed event-related and epoch-based paradigms (mixed designs) have recently been
      introduced as viable experimental designs for fMRI studies. To date, mixed
      designs have been used only to evaluate transient and state changes that are
      associated with single event and blocked conditions, respectively. However, no
      study exists that demonstrates that the regional activity associated with two
      distinct processes with known activation patterns can be adequately separated.
      Rapid event-related experimental designs use the principles of linear summation
      and can identify multiple distinct processes that are not overlapping in time
      through linear regression. Events and epochs that are also separated in time can
      be easily distinguished using the same general linear model (GLM) and a multiple
      regression analysis. However, it may not be so obvious that events that are
      superimposed in time onto epochs can also theoretically be separated using this
      technique. We used the principles of linear summation and the GLM to demonstrate
      that regional activity from a mixed design with visual epochs and auditory events
      superimposed in time can in fact be separated. In addition, the flexibility of
      mixed designs is explored using a paradigm that includes events throughout the on
      and off blocks of the epoch-based paradigm. Mixed designs provide neuroscientists
      with the power and flexibility to address more complex cognitive hypotheses that
      were otherwise difficult to study with either epoch-based or event-related
      designs alone.

PMID- 14659824
TI  - The simultaneous in vivo perilymphatic perfusion of avian auditory and vestibular
      end organs.
AB  - Perilymphatic perfusion is a method that allows the control of fluid parameters
      throughout the perilymphatic space of the inner ear. We have evaluated a new
      method for continuous perilymphatic perfusion of the auditory and vestibular end
      organs with artificial perilymph (APL) in chickens. Perfusate temperature (39.0
      degrees C), pH (7.4), osmolarity (328 +/- 2 mosm), and flow rate (2 microl/min)
      were carefully controlled. Independent functional tests of vestibular and
      auditory sensory systems were made throughout perfusion periods by recording
      peripheral compound action potentials (CAPs). The recordings provided a means of
      monitoring the status of hair cell transduction, synaptic transmission and
      collective primary afferent activation in response to auditory or vestibular
      gravity receptor stimuli. Auditory and vestibular responses were stable during
      perfusion. No significant changes occurred in vestibular or auditory CAP
      amplitudes during long-term perfusion (50-80 min, n=7) and responses remained
      stable in one animal perfused for over 3 h. To our knowledge, there have been no
      reports evaluating vestibular function under these conditions. This technique
      enables us to systematically study receptor pharmacology in the peripheral
      vestibular and auditory systems virtually simultaneously in vivo. The model is
      well suited for use in the study of the pharmacology and toxicology of inner ear
      sensory systems.

PMID- 14659823
TI  - Short interfering RNAs (siRNAs) for reducing dopaminergic phenotypic markers.
AB  - Short interfering RNAs (siRNAs) are double-stranded RNAs of approximately 19-29
      nucleotides designed to suppress the expression of homologous genes by a process
      known as RNA interference (RNAi). In this study we have characterized several
      short interfering RNAs to reduce (knockdown) the expression of genes related to
      the dopaminergic system of the ventral mesencephalon. We report here effective
      suppression of all targeted genes, tyrosine hydroxylase (TH), the transcription
      factor Nr4a2 (Nurr1) and the GDNF receptor moiety cRet, by co-transfection of
      plasmids expressing gene specific siRNAs under control of the human U6 promoter
      with a reporter plasmid coding for firefly luciferase and fused in tandem to the
      cDNA for the gene of interest. The effective suppression of Nr4a2, cRet and
      tyrosine hydroxylase suggest that the U6 expression cassette could be used to
      deliver siRNA to mammalian cells in vivo and actively suppress the expression of
      dopamine related mammalian genes. The characterization of highly effective siRNAs
      for DA phenotypic markers may open new avenues for loss-of-function phenotypic
      analysis, and may lead to new approaches for gene therapy.

PMID- 14659825
TI  - Segmentation of magnetic resonance brain images through discriminant analysis.
AB  - Segmentation (tissue classification) of medical images obtained from a magnetic
      resonance (MR) system is a primary step in most applications of medical image
      post-processing. This paper describes nonparametric discriminant analysis methods
      to segment multispectral MR images of the brain. Starting from routinely
      available spin-lattice relaxation time, spin-spin relaxation time, and proton
      density weighted images (T1w, T2w, PDw), the proposed family of statistical
      methods is based on: (i) a transform of the images into components that are
      statistically independent from each other; (ii) a nonparametric estimate of
      probability density functions of each tissue starting from a training set; (iii)
      a classic Bayes 0-1 classification rule. Experiments based on a computer built
      brain phantom (brainweb) and on eight real patient data sets are shown. A
      comparison with parametric discriminant analysis is also reported. The capability
      of nonparametric discriminant analysis in improving brain tissue classification
      of parametric methods is demonstrated. Finally, an assessment of the role of
      multispectrality in classifying brain tissues is discussed.

PMID- 14659826
TI  - Continuous measurement of intracranial pressure in awake rats after experimental
      closed head injury.
AB  - The present study validates a method for continuous measurement of intracranial
      pressure (ICP) in freely moving rats after experimental induction of impact
      acceleration injury. Rats subjected to either mild or moderate trauma were
      individually placed in a Bas-Ratturn system, equipped with a sensor that
      synchronously turns the cage in response to the locomotor activity of the animal.
      In this way correct probe positioning is permanently assured and damage due to
      coiling is avoided. The evolution of ICP and mean arterial blood pressure (MABP)
      in injured rats was compared with that of a non-traumatized sham group. Since the
      animals regained consciousness after surgery, interference of anaesthesia on
      these sensitive parameters should be minimised. The results showed that
      immediately after induction of neurotrauma, ICP was significantly higher in
      traumatized rats (sham: 7.7 +/- 0.5 mmHg; mild trauma: 10.4 +/- 0.7 mmHg;
      moderate trauma: 14.9 +/- 2.4 mmHg; P<0.05). Regression analysis showed a stable
      ICP up to 3 h post-insult for all three conditions. From 4 h onwards till the end
      of the experiment at 10 h post-insult, a significant increase in ICP was seen for
      sham-operated and mildly traumatized rats (16.1 +/- 3.4 and 30.5 +/- 6.9 mmHg,
      respectively; P<0.05), but not for moderately traumatized rats (47.3 +/- 11.9
      mmHg). The method allows observation of ICP for a critical period up to 3 h. As
      such the method can be regarded as clinically relevant to study early
      pathological aspects of intracranial hypertension and to define a therapeutic
      window for pharmacological intervention after traumatic brain injury (TBI).

PMID- 14659827
TI  - Quantification of layer-specific gene expression in the hippocampus: effective
      use of laser microdissection in combination with quantitative RT-PCR.
AB  - Laser microdissection in combination with quantitative RT-PCR is now widely
      appreciated as an excellent tool for quantifying mRNA levels in defined cell
      populations. It may be particularly useful in the hippocampal formation, where
      principal cells form distinct and readily identifiable cell layers. Here we are
      presenting an optimized protocol for labeling hippocampal principal cells on foil
      mounted sections for microdissection with the Leica AS LMD system and discuss
      potential further applications and pitfalls. Employing this optimized method, we
      studied changes in brain-derived neurotrophic factor (BDNF) mRNA expression in
      granule cells of the mouse dentate gyrus following unilateral entorhinal cortex
      lesion. In this lesioning paradigm, changes in BDNF mRNA expression have
      previously been reported in the rat. Using laser microdissection, the granule
      cell layers ipsi- and contralateral to the lesion were collected and changes in
      BDNF levels were quantified using quantitative RT-PCR. BDNF mRNA levels were five
      fold higher on the ipsilateral side compared to levels found on the contralateral
      side or in controls. The development of this optimized method for laser
      microdissection and subsequent quantitative RT-PCR allows layer-specific
      quantification of gene expression levels in the hippocampus and may be similarly
      employed in other brain areas or tissues with a laminar arrangement or high
      density of cells.

PMID- 14659828
TI  - Optimization of the mechanical nociceptive threshold testing with the Randall
      Selitto assay.
AB  - The Randall-Selitto (RS) assay is widely used for quantification of thresholds of
      the rat hindpaw withdrawal reflex to nociceptive pressure stimulation. Despite a
      report by Taiwo et al. [Brain Research 487 (1989)] that the sensitivity of the RS
      assay can be significantly improved by pre-training, many researchers still
      conduct this test in untrained rats. In part, this is because the study of Taiwo
      et al. employed heavily-restrained and thus very stressed animals. That study
      also examined bradykinin-induced hyperalgesia rather than hyperalgesia associated
      with persistent inflammatory models used in many other studies. Therefore, it is
      conceivable that pre-training may be unnecessary with a less restraining RS
      testing paradigm and the use of inflammation-producing agents. To resolve these
      issues, we re-examined the need for pre-training with the RS assay with minimal
      animal restraint and inflammation produced by Complete Freund's Adjuvant (CFA)
      injection. We also examined the sensitivity of this assay to detect analgesia
      induced by swim stress. We found that without training the differences between
      untreated, CFA-injected, swim stress-exposed, and CFA + swim stress-treated
      animal groups did not reach statistical significance. Four days of training,
      however, enlarged these differences to statistically significant levels.
      Furthermore, we found that the use of only the last measurement within a testing
      session, rather than the average of all collected measurements, may further
      enhance the sensitivity of the RS assay.

PMID- 14659829
TI  - The evaluation of brain activity in response to taste stimuli--a pilot study and
      method for central taste activation as assessed by event-related fMRI.
AB  - BACKGROUND: Brain pathways contribute to the regulation of appetite behaviors,
      and advancements in brain imaging offer new opportunities in determining whether
      disturbances of these pathways play a role in pathological feeding behaviors in
      humans. We developed a standardized method for the assessment of brain activation
      in response to taste stimuli. METHODS: Five healthy control women were positioned
      in a 1.5 T GE magnet resonance (MR) scanner for functional MR imaging (fMRI).
      They received 1.0 cm3 samples of 1 M glucose solution or artificial saliva (25 mM
      KCl, 2 mM NaHCO3). Fluid challenges were delivered by a programmable syringe pump
      (J-Kem Scientific, St. Louis, MO). E-Prime software (Psychology Software Tools
      Inc., Pittsburgh, PA) coordinated taste stimulation with MR scanning. Data were
      analyzed using NeuroImaging software (NIS). RESULTS: Healthy women showed
      increased orbitofrontal cortex activation when glucose was compared to artificial
      saliva. In addition, mesial and lateral temporal cortical regions contrasted
      glucose from artificial saliva. CONCLUSIONS: This study demonstrates a design for
      the systematic study of brain activation after taste stimulation using fMRI and
      computer controlled stimulus delivery. The results are consistent with previous
      studies, showing activation in higher order brain centers that are involved in
      emotional coding of taste experience.

PMID- 14659830
TI  - A simple method for fabricating horizontal and vertical microwire arrays.
AB  - Microwire array electrodes are important in multi-site, multiple single-unit
      recording experiments. A simple method is described herein for the construction
      of microwire arrays consisting of evenly spaced insulated microwires in either
      horizontal or vertical orientations. Several key steps in the fabrication of a
      good microwire array electrode are made easier with this method. These steps
      include (1) arranging microwires into a desirable configuration, (2) keeping
      track of microwire sequences, and (3) soldering microwires to closely packed
      slots. This method needs only general mechanical tools and is relatively simple
      even for inexperienced workers.

PMID- 14659831
TI  - A state-dependent trigger for electrophysiological recording at predetermined
      membrane potentials.
AB  - This paper describes the circuitry and construction of a novel electronic
      threshold discriminator, and details its specific application to in vivo
      intracellular recording. The discriminator reliably triggers electrophysiological
      recording at pre-selectable membrane potentials in neuronal systems that exhibit
      membrane potential oscillations. It has been used successfully whilst recording
      from spiny projection neurons of the striatum to measure membrane properties and
      trigger electrical stimulation within either of two discrete membrane potential
      "states". The device works by comparing the analogue membrane potential waveform
      with a user-defined threshold membrane potential, and outputs a logic signal to
      flag the occurrence of a threshold-crossing event. This signal is used to trigger
      the commencement of episodic recording and the application of current injection
      or electrical stimulation at a consistent membrane potential. Thus, the
      discriminator acts as a functional clamp to isolate evoked responses from
      endogenous fluctuations in membrane potential. The unit uses cheap and easily
      available components and can be constructed with the minimum of electronics
      experience. It could be adapted to isolate discrete events within any oscillatory
      system.

PMID- 14659832
TI  - The isolation and culture of microglia-like cells from the goldfish brain.
AB  - We have developed a method for isolating goldfish microglia. Cells were
      identified as microglia immunohistochemically with NN-2, a monoclonal antibody
      (MAb) raised against teleost retinal microglial cells, and by their phagocytic
      abilities. Morphological characterization of the cells identified round, phase
      bright cells as well as flattened macrophage-like cells. Ramified cells were also
      seen but they were rare. Fusion of macrophage-like cells occurred in high density
      cultures and resulted in the formation of giant cells that disintegrated a few
      days later. Immunohistochemical studies demonstrated that virtually all of the
      cells in our cultures were NN-2+ and did not label with either antiGFAP (an
      astrocyte marker) or MAb 6D2 (an oligodendrocyte marker). Cells identified as
      microglia were intensely phagocytic and ingested latex microspheres, DiIAcLDL and
      goldfish myelin in vitro. In addition, we labelled microglial cells in vivo with
      intracranial injections of fluorescent dextran and found that microglia isolated
      from these animals contained the dextran and phagocytosed microspheres. We also
      studied the effect of myelin on microsphere uptake and compared the effect of
      myelin and opsonized myelin on the phagocytic activity of the cells. Our results
      showed a clear increase in the phagocytic activity of microglia when incubated
      with myelin, with an enhanced effect of opsonized myelin.

PMID- 14659833
TI  - Primary culture of cortical neurons, type-1 astrocytes, and microglial cells from
      cynomolgus monkey (Macaca fascicularis) fetuses.
AB  - We established selective primary cultures of neurons, astrocytes, and microglial
      cells from cryopreserved fetal cerebral cortex of cynomolgus monkeys (Macaca
      fascicularis). At 14 days in serum-containing medium, the cell cultures of the
      fetal cerebral cortex consisted primarily of neurons, astrocytes, and floating
      microglial cells. At 21 days, we observed a small number of myelin basic protein
      (MBP)-positive oligodendrocytes. The addition of cytosine arabinoside (a
      selective DNA synthesis inhibitor) at 2 days in culture eliminated proliferative
      glial cells, allowing adequate numbers of neurons to survive selectively. A
      chemically defined serum-free medium successfully supported neuronal survival at
      a level equivalent to that supported by the serum-containing medium. Brain
      derived neurotrophic factor (BDNF) significantly affected the survival of primate
      neurons. Glutamate induced a significant degree of neuronal cell death against
      primate neurons and MK-801, a selective N-methyl-D-aspartate receptor (NMDAR)
      antagonist, blocked cell death, which suggests that primate cortical neurons have
      NMDAR and the glutamate-induced cell toxicity is mediated by NMDAR. In the serum
      free medium, type-1 astrocytes responded to dibutyryl cyclic AMP and showed a
      process-bearing morphology. The growth of type-1 astrocytes in the serum-free
      medium was stimulated by epidermal growth factor (EGF), basic fibroblast growth
      factor (bFGF), and hydrocortisone, which are known growth factors in rat type-1
      astrocytes. Cultured microglial cells expressed CD68, a monocyte marker.
      Macrophage-colony stimulating factor (M-CSF) stimulated microglial cell growth in
      the serum-free medium. These selective primary culture systems of primate
      cerebral cortical cells will be useful in issues involving species specificity in
      neuroscience.

PMID- 14659834
TI  - Ink-jet printing for micropattern generation of laminin for neuronal adhesion.
AB  - In order to achieve defined adhesion and neurite outgrowth, the growth substrate
      must be patterned in an appropriate way. We utilised ink-jet printing by means of
      a piezo-based microdispenser to create defined line patterns of a polymer with
      typical dimensions of 100 microm width on glass, silicon, gold and carbon
      substrates. Vinnapas, a co-polymer of vinyl acetate and ethylene, was mixed with
      the extracellular matrix protein laminin to achieve neuronal adhesion on the
      surface of the patterns. It could be demonstrated that the laminin entrapped in
      the polymer lines can be recognised by a specific antibody. Adhesion of embryonic
      chicken forebrain neurones is following the prepared lines, and identity of
      adhering cells could be shown by neurofilament staining. These findings open the
      route for the generation of complex small neuronal arrays and for the
      electrochemical investigation of the obtained neuronal matrix.

PMID- 14659835
TI  - High-resolution fragmentary decomposition--a model-based method of non-stationary
      electrophysiological signal analysis.
AB  - Fragmentary decomposition (FD) is a recently developed method of non-stationary
      electrophysiological signal analysis addressed to mass potentials, such as
      electromyogram (EMG), event-related potential (ERP), evoked potential,
      electroencephalogram (EEG), electroretinogram, etc. Being supported by the
      generally accepted physiological notion that a peak is a functionally meaningful
      component of a mass potential, FD provides a way to avoid averaging and, instead,
      quantifies the component composition of complex electrophysiological signals
      directly from single-trials. The major computational procedures of FD include
      adaptive segmentation, the frequency domain component identification, and
      creation of the signal model as a linear aggregation of multiple components, with
      the generic mass potential (GMP) being the universal component template. This
      paper presents an improved, high-resolution FD technique which allows the
      resolution of overlapping sub-components and supports each identified component
      by an individual model. On the basis of this methodological innovation, we define
      two fundamental categories of multi-peak component waveforms: complex components
      (CC), comprised of multiple sub-components (GMPs), versus monolithic components
      (MC), involving a single GMP. We show that quantification of MCs and CCs from
      single-trial eyeblink EMG and single-trial ERP provides a more comprehensive
      analysis of these signals. Given single-trial eyeblink EMG, we find that the
      stimulus elicits strong though short-term (phasic) effects on MCs and moderate
      but long-lasting (tonic) effects on CCs. A new realm of single-trial ERP
      quantification is possible in that the MC appears as a marker of a single
      cognitive variable whereas the CC appears as a marker of a series of functionally
      related cognitive variables. The engagement of the brain in a specific cognitive
      task is accompanied by an increase of CCs in single-trial ERPs, which is
      especially informative with respect to the P3 cognitive potential. New
      methodology provides evidence for the three basic types of single-trial P3 sub
      components: monolithic P3a, monolithic P3b, and a complex component, P3ab, which
      includes both P3a and P3b as sub-components.

PMID- 14659836
TI  - Retinotopic mapping in cat visual cortex using high-field functional magnetic
      resonance imaging.
AB  - In the field of neuroscience, there has always been a need for imaging techniques
      that provide high-resolution, large field-of-view measurements of neural
      activity. Functional MRI has this capability, but the link between the blood
      oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI)
      signal and neural activity is indirect. High magnetic field strengths (>3 T)
      improve the strength and specificity of the BOLD signal, but there are additional
      concerns about imaging artifacts at high field. We have tested the capabilities
      of ultra high field fMRI in the anesthetized juvenile cat, demonstrating rapid,
      non-invasive retinotopic mapping of early visual areas. Maps of topographic
      organization and measured cortical magnification factors are in good agreement
      with electrophysiological studies. Measurement precision was estimated at 1 mm.
      This mapping, performed with an MRI scanner at ultra high field (9.4 T),
      demonstrates the capabilities of high-resolution functional mapping of the visual
      system at ultra high field.

PMID- 14659837
TI  - A multi-channel correlation method detects traveling gamma-waves in monkey visual
      cortex.
AB  - Correlations among simultaneously recorded signals are mostly analyzed pairwise
      and include temporal averaging. However, pairwise methods are not suitable for
      characterizing relationships among multiple channels for signals which vary
      temporally in an unpredictable way. Here we develop a time-resolved spatio
      temporal correlation (STC) measure among simultaneously recorded signals. We
      demonstrate the capabilities of the method with artificial data sets and with
      multiple-channel recordings from striate cortex of awake monkeys. We concentrate
      on correlations in the gamma-frequency range (gamma: 30-90 Hz) because they were
      prominent in the analyzed recordings and gained high interest in the recent years
      due to their assumed role in associative processing, including perceptual
      binding. Former analyses of gamma-activities in visual cortex, using pairwise
      correlation methods, mostly revealed zero-delay correlation, indicating
      synchrony. In cat and monkey visual cortex this gamma-synchrony is restricted to
      1.5-3.0 mm (half-height decline). However, our spatio-temporal correlation (STC)
      method demonstrates for striate cortex from awake monkeys that gamma-synchrony is
      a local phenomenon of more global traveling plane waves that appear stimulus
      induced at randomly varying orientations. These gamma-waves are coupled over much
      larger cortical distances (approximately 7 mm half-height decline) than the gamma
      synchrony ranges obtained by pairwise correlation analyses from the same data.
      Our STC-method therefore suggests that the previously reported results of short
      range and zero-delay correlations were often due to temporal averaging of
      traveling gamma-waves.

PMID- 14659838
TI  - Fractionated analysis of paired-electrode nerve recordings.
AB  - Multi-unit activity recorded from two electrodes positioned at a distance on a
      nerve may be analysed by cross-correlation, but units similar in direction and
      velocity of propagation cannot be distinguished and separately evaluated by this
      method. To overcome this limit, we added two features, represented by the impulse
      amplitudes of the paired recordings, to the dimension given by the impulse delay.
      The analysis was fractionated according to the new dimensions. In experimental
      recordings from the locomotor appendage of the lobster Homarus americanus, the
      fractionated analysis proved capable of identifying the contributions of single
      active units, even if these were superimposed and indiscernible in the global
      cross-correlation histogram. Up to 5 motor and 10 sensory units could be
      identified. The shape of the paired impulses was evaluated by an averaging
      procedure. Analogous evaluations on simulated recordings made it possible to
      estimate the influences exerted on performance by variations in noise level and
      in the number and firing rate of active units. The global signal could be
      resolved into single units even under the worst conditions. Accuracy in
      evaluating the amount of unit activity varied, exceeding 90% in about half of the
      cases tested; a similar performance was attained by evaluation of the impulse
      shapes.

PMID- 14659839
TI  - Analyzing the reflections from single ommatidia in the butterfly compound eye
      with Voronoi diagrams.
AB  - This paper presents a robust method for the automated segmentation and
      quantitative measurement of reflections from single ommatidia in the butterfly
      compound eye. Digital pictures of the butterfly eye shine recorded with a digital
      camera are processed to yield binary images from which single facet centers can
      be extracted using a morphological image analysis procedure. The location of the
      facet centers is corrected by fitting in-line facet centers to a second-order
      polynomial. Based on the new centers a Voronoi diagram is constructed. In the
      case of the eye shine images, the Voronoi diagram defines a hexagonal lattice
      that overlaps with the original facet borders, allowing instantaneous
      quantification of the reflections from single ommatidia. We provide two typical
      examples to demonstrate that the developed technique may be a powerful tool to
      characterize in vivo the heterogeneity of butterfly eyes and to study the dynamic
      control of the light flux by the pupil mechanism.

PMID- 14659840
TI  - Gene expression patterns in rat dentate granule cells: comparison between fresh
      and fixed tissue.
AB  - RNA from brain tissue (in particular human brain) can often only be extracted
      from fixed material. As brain tissue is very heterogeneous with regard to cell
      type, it is important to obtain RNA from small samples of identified cells. The
      aim of this study was (a) to generate expression profiles from small yet
      homogeneous samples of fixed brain cells in rat and (b) to verify the reliability
      of these profiles by comparing them with expression profiles obtained from single
      fresh neurons of the same cell type. Samples (n=12) of 50 rat dentate granule
      cells were isolated, using Laser Microdissection and Pressure Catapulting, from
      paraformaldehyde fixed, paraffin embedded tissue or from frozen, ethanol fixed
      tissue. In addition, RNA was extracted under visual control from individual
      dentate granule cells (n=12) in hippocampal slices, after electrophysiological
      recording with patch clamp electrodes. Our data show that RNA was successfully
      extracted from ethanol fixed sections yielding expression profiles highly
      comparable to those from non-fixed, single granule cells. RNA extraction from
      paraformaldehyde fixed, paraffin embedded tissue was less reliable. The present
      approach validates expression profiling from small amounts of fixed neurons as a
      powerful tool to investigate molecular processes if fresh tissue is not
      available.

PMID- 14659841
TI  - Information and communication technology in cardiovascular disease prevention in
      developing countries: hype and hope. Report of the International Collaboration on
      Information Use in Cardiovascular Health Promotion in Developing Countries.
AB  - Information can be an important tool in promoting a prevention strategy to
      address the emerging epidemic of cardiovascular disease in developing countries.
      Advances in information and communication technology offer new promises for
      global access to information and for global mobilization to prevent and control
      cardiovascular disease. This is especially true for health professionals, whose
      needs in areas such as networking, exchange of expertise and access to relevant
      advances remain unfulfilled. Information technology can also sensitize the lay
      public to the magnitude of cardiovascular diseases, creating awareness about risk
      states, and highlighting preventive strategies. Effective application mandates
      that the technology be relevant to local needs. Cost, feasibility, and relevance
      of information need to be considered before wide adoption is advocated. Several
      initiatives, such as ProCOR, Global Cardiovascular Infobase, Heartfile, and the
      Virtual Congress of Cardiology, have successfully utilized information technology
      to promote cardiovascular prevention. The experience of these initiatives
      suggests that, while information technology holds great potential, there are many
      potential perils, such as the widening global information gap, inequitable
      access, and irrelevant information. For now, information technology must be
      viewed as part of a broader strategy, which includes conventional communication
      media, to address the unmet information needs for cardiovascular prevention
      globally. Enlightened policies can exploit the energies of the recent information
      boom for promoting cardiovascular prevention, taking into account the considered
      limitations.

PMID- 14659842
TI  - Atrial stunning: basics and clinical considerations.
AB  - Conversion of atrial fibrillation and flutter to sinus rhythm results in a
      transient mechanical dysfunction of atrium and atrial appendage, termed atrial
      stunning. Atrial stunning has been reported with all modes of conversion of
      atrial fibrillation and flutter to sinus rhythm including both transthoracic and
      low energy internal electrical, pharmacological, and spontaneous cardioversion,
      and conversion by overdrive pacing and by radiofrequency ablation. Atrial
      stunning is a function of the underlying arrhythmia becoming apparent at the
      restoration of sinus rhythm, not the function of the mode of conversion, and does
      not develop after the unsuccessful attempts of cardioversion or the delivery of
      electric current to the heart during rhythms other than atrial fibrillation or
      flutter. Tachycardia-induced atrial cardiomyopathy, cytosolic calcium
      accumulation, and atrial hibernation are the suggested mechanisms of atrial
      stunning. Atrial stunning is at maximum immediately after cardioversion and
      improves progressively with a complete resolution within a few minutes to 4-6
      weeks depending on the duration of the preceding atrial fibrillation, atrial
      size, and structural heart disease. Atrial stunning causes postcardioversion
      thromboembolism despite restoration of sinus rhythm. Duration of anticoagulation
      therapy after successful cardioversion should depend on the duration of atrial
      stunning. Lack of improvement in cardiac output and functional recovery of
      patients immediately after cardioversion is attributed to the atrial stunning.
      Verapamil, acetylstrophenathidine, isoproterenol, and dofetilide have been
      reported to protect from atrial stunning in animal and small human studies. Right
      atrium stunning is less marked and improves earlier than that of left atrium,
      resulting in a differential atrial stunning explaining the rare occurrence of
      pulmonary edema after cardioversion.

PMID- 14659843
TI  - Why does C-reactive protein increase in non-ST elevation acute coronary
      syndromes? Role of myocardial damage.
AB  - INTRODUCTION: C-reactive protein is an important prognostic indicator for early
      risk stratification in patients with an acute coronary syndrome. The mechanisms
      underlying the elevation of C-reactive protein in these patients have not been
      fully understood. We studied the factors related to the increase of this acute
      phase reactant. METHODS AND RESULTS: Within a single-centre registry, 419
      consecutive patients admitted for a non-ST elevation acute coronary syndrome were
      studied. Serum high sensitivity C-reactive protein was measured late (median 3
      days) after admission. Clinical, electrocardiographic, biochemical and
      angiographic variables were recorded. In the multivariate analysis, an increased
      C-reactive protein (n=162) was related to high levels of troponin I (OR 2.5 (1.6
      4) P<0.001) and to a Killip class>1 at presentation (OR 2.9 (1.6-5.4) P<0.001).
      The coronary angiographic characteristics were not related to C-reactive protein.
      Finally, in 52 patients with no previous heart disease in whom regional
      dysfunction was quantified by left ventriculography the presence of a significant
      (>6 chords) regional dysfunction was significantly related to C-reactive protein
      (OR 5.1 (1.7-15.3) P=0.006) CONCLUSION: Our results indicate that in acute
      coronary syndromes elevated levels of C-reactive protein late after admission are
      mainly related to clinical, biochemical and angiographic evidences of myocardial
      damage. The prognostic utility of this parameter could be in part explained by
      its relationship with a major regional dysfunction.

PMID- 14659844
TI  - Role of LDL receptor-related protein (LRP) in coronary atherosclerosis.
AB  - The development and progression of coronary atherosclerosis is influenced by a
      variety of genetic and environmental factors. Among the genetic factors, the cell
      surface receptor LRP/A2MR (LDL receptor-related protein/alpha2-macroglobulin
      receptor) was shown to be involved in a variety of biological processes leading
      to atherosclerotic plaque formation. That is why the individual expression of
      this receptor may, therefore, be considered as an evident predictor for coronary
      atherosclerosis. In this clinical ex vivo study the expression was measured by
      competitive RT-PCR and macroarray analysis in native monocytes. Both methods were
      first tested in an in vitro model using different human cells and cell lines
      (fibroblasts: chorion, skin; endothelial cells from umbilical cord vein; monocyte
      cell line: Mono-Mac-6): after stimulation with an LRP/A2MR ligand, leptin, the
      anticipated direct effect of this ligand, namely an increase in both receptor
      mRNA and protein expression, was confirmed. In disease-related ex vivo studies
      the mRNA and protein-expression of LRP/A2MR was investigated in 36 male patients
      suffering from myocardial infarction. In comparison to the control group (36
      healthy male blood donors), a significant up-regulation of mRNA was detected in
      the myocardial infarction patient group (control: 122.3 ag/cell versus patients:
      223 ag/cell; P<0.001). Investigating the LRP/A2MR protein expression a
      significant down-regulation of protein expression was determined in the patient
      group (control: 6 pg/cell versus patients: 1.6 pg/cell; P<0.001). The ratio of
      LRP/A2MR mRNA and protein expression is obviously an evident marker for coronary
      atherosclerosis, recommendable for the assessment of the individual coronary risk
      profile.

PMID- 14659845
TI  - Persistent atrial fibrillation: a population based study of patients with their
      first cardioversion.
AB  - BACKGROUND: Electrical cardioversion is effective in terminating even long
      standing atrial fibrillation (AF), but the relapse risk of AF is high. Data on
      long-term success of cardioversion in real life clinical practice are scant.
      METHODS: Restoration and maintenance of sinus rhythm as well as acceptance of
      permanent AF was studied in a population based cohort (catchment area with a
      population of 440,000) of patients with persistent AF after first elective
      cardioversion. RESULTS: Of the 183 patients having their first electrical
      cardioversion during the 1-year study period, sinus rhythm was restored in 153
      patients (84%). Only 39 of these (25%) maintained sinus rhythm for 1 year, even
      though 108 (71%) patients had anti-arrhythmic medication. Age, hypertension,
      coronary artery disease, heart failure and valvular disease, or absence of these
      known risk factors for AF were not associated with the outcome. The outcome was
      better if the cardioversion was performed earlier than the median delay (78 days)
      from the diagnosis of AF to cardioversion compared to longer delay (P=0.022 in
      multivariate modelling). The decision of acceptance of permanent AF was made in
      74 cases (40%) during 1 year of follow-up. CONCLUSIONS: Patients with persistent
      AF had a high tendency to remain in or relapse into AF, even though most patients
      had anti-arrhythmic medication after first cardioversion. Short history of
      arrhythmia was associated with better outcome. Acceptance of permanent AF was
      made in almost half of the cases during 1 year of follow-up.

PMID- 14659846
TI  - Noninvasive evaluation of the prevalence of noncalcified atherosclerotic plaques
      by multi-slice detector computed tomography: results of a pilot study.
AB  - BACKGROUND: Multi-slice detector computed tomography (MDCT) not only allows for
      the determination of coronary calcifications, but also for the noninvasive
      visualization of noncalcified plaques. Thus, coronary artery disease (CAD) can be
      detected at a fairly early stage. Since data on the prevalence of potentially
      rupture prone noncalcified coronary lesions are still missing, it was aim of the
      present investigation to study this in patients with a distinct cardiovascular
      risk profile, but without known CAD. METHODS: 68 patients with clinical suspicion
      of CAD and multiple cardiovascular risk factors were included in this prospective
      study. Calcium scoring, as well as the detection of noncalcified plaques were
      performed using a Somatom VZ scanner (Siemens, Forchheim, Germany). RESULTS:
      Calcium scoring could be performed in all patients on native scans; 63/68 (96%)
      of contrast enhanced scans showed sufficient image quality to perform a screening
      for noncalcified plaques. The three scans without diagnostic image quality had
      been performed at heart rates of 95 +/- 18/min. Coronary calcifications were
      found in 36/65 (55%) patients (Agatston score: 247 +/- 358). Additional
      noncalcified plaques were detected in 16/36 (45%) of these patients; 29/65 (45%)
      patients had no coronary calcifications (Agatston score: 0), but noncalcified
      plaques could be detected in 3/29 (10%) of these patients. CONCLUSIONS: The
      prevalence of noncalcified plaques was 29% in the whole study group, and even in
      10% of patients without coronary calcifications. Further prospective large scale
      studies are required to confirm these data, and to evaluate the clinical
      implication of this finding.

PMID- 14659847
TI  - Usefulness of technetium-99m sestamibi myocardial perfusion SPECT in detection of
      cardiovascular involvement in patients with systemic lupus erythematosus or
      systemic sclerosis.
AB  - The main purpose of the study was to evaluate the utility of technetium-99m
      sestamibi myocardial perfusion single-photon emission computed tomography (Tc-99m
      sestamibi SPECT) in detection of cardiac involvement in systemic lupus
      erythematosus (SLE) or systemic sclerosis (SS) patients. Fifty SLE or SS female
      patients with cardiac symptom/sign such as chest discomfort and/or dyspnea and/or
      occasionally palpitation and 50 SLE or SS female patients without any cardiac
      symptom/sign were investigated using Tc-99m sestamibi SPECT during rest and
      stress after dipyridamole infusion. Twenty-five age- and sex-matched healthy
      females were also included as controls in this study. The results of Tc-99m
      sestamibi SPECT were classified into four types including normal, persistent
      perfusion defect (PD), reversible perfusion defect (RD), and reverse perfusion
      defect (RR). The results of Tc-99m sestamibi SPECT in the 25 healthy females were
      normal. Perfusion abnormalities were detected in 44/50 (88%) symptomatic SLE or
      SS patients. However, myocardial perfusion abnormalities were only detected in
      19/50 (38%) asymptomatic SLE or SS patients (P value<0.05 by a chi2 test).
      However, for risk factor of coronary artery disease and abnormal resting EKG, the
      incidences were not significant between symptomatic and asymptomatic patients (P
      values >0.05 by a chi2 test). Tc-99m sestamibi SPECT is a useful noninvasive
      imaging modality to detect cardiac involvement in symptomatic or asymptomatic SLE
      or SS patients.

PMID- 14659848
TI  - Elevated donor cardiac troponin T and procalcitonin indicate two independent
      mechanisms of early graft failure after heart transplantation.
AB  - BACKGROUND: Cardiac troponin T (cTnT) >0.1 microg/l and procalcitonin (PCT) >2
      microg/l in the serum of heart donors are predictors of early graft failure after
      heart transplantation (HTx). The current study investigates the relationship
      between these two markers and their prognostic value when one or both of them are
      elevated. METHODS: Cardiac TnT and PCT were measured in serum from 92 consecutive
      brain-dead donors accepted for HTx. The donors were retrospectively divided into
      two groups: group I (n=78) donors of hearts with good function, group II (n=14)
      donors of hearts with early graft failure after transplantation. RESULTS: There
      were no correlations between cTnT and PCT values (r=0.12, P=0.27). In eight
      donors in group I one or both markers were elevated. In one donor both markers
      were above the cut-off levels. In 12 donors (86%) in group II one or both markers
      were elevated. In two donors both markers were above the cut-off levels and in a
      further two below. There was no significant interaction between the two markers
      in either group using a logistic regression model (P=0.28). CONCLUSIONS: Elevated
      cTnT and PCT levels in the serum of heart donors were independent prognostic
      markers of early graft failure. This fact may suggest two different mechanisms of
      early graft failure: primary myocardial damage and damage related to systemic
      inflammatory response. The combination of both markers had a higher sensitivity
      than each parameter on its own. Their use as additional parameters may improve
      heart donor selection.

PMID- 14659849
TI  - Anti-inflammatory cytokine profile in acute coronary syndromes: behavior of
      interleukin-10 in association with serum metalloproteinases and proinflammatory
      cytokines.
AB  - BACKGROUND: The anti-inflammatory cytokine interleukin-10 (IL-10) downregulates
      the production of metalloproteinases (MMPs) and upregulates the production of
      their tissue inhibitors (TIMPs). The aim of this study was to assess the levels
      of IL-10 in patients with acute myocardial infarction (AMI) and unstable angina
      (UA), as well as to investigate the relationship of circulating IL-10 with the
      levels of MMPs (MMP-1, -2, -9), their tissue inhibitor (TIMP-1), pro-inflammatory
      cytokines (IL-6, tumor necrosis factor (TNF)-alpha) and serum lipids in the same
      patient population. METHODS: Serum MMP-1, -2, -9, TIMP-1, IL-6, TNF-alpha and IL
      10 were measured by ELISA assays in 23 patients with AMI and 20 patients with UA
      after their hospital admission, as well as in 16 healthy controls subjects. The
      lipid profile was assessed by measuring the serum levels of total cholesterol,
      HDL-cholesterol, LDL-cholesterol and triglycerides. RESULTS: AMI patients
      exhibited significantly higher serum levels of IL-10 as compared with those of UA
      patients and healthy controls (both P=0.005). In contrast, there was no
      significant difference in IL-10 levels between UA patients and healthy controls.
      In AMI patients there was a statistically significant positive correlation of
      serum IL-10 with the levels of MMP-9 (rho=0.588, P=0.003), IL-6 (rho=0.502,
      P=0.015) and HDL-cholesterol (rho=0.697, P<0.001), as well as a significant
      negative correlation with the levels of triglycerides (rho=-0.417, P=0.048).
      CONCLUSIONS: Our results suggest that UA is associated with low serum activity of
      IL-10, while a significant elevation of this anti-inflammatory cytokine
      accompanies the peripheral immune responses of AMI. This observation indicates
      that different patterns of inflammatory reactions are implicated in the
      pathophysiology of two clinical conditions.

PMID- 14659850
TI  - Release of matrix metalloproteinase-9 during balloon angioplasty in patients with
      stable angina. A preliminary study.
AB  - BACKGROUND: Vascular wall remodeling is a major factor contributing to restenosis
      after angioplasty that involves migration and proliferation of vascular smooth
      muscle cells. The release of matrix-degrading metalloproteinases, including
      metalloproteinase-2 and metalloproteinase-9, facilitates remodeling. Experimental
      data suggest that nitric oxide (NO) decreases the activity of metalloproteinases
      and this may attenuate arterial remodeling after balloon injury. We investigated
      whether metalloproteinase-2, metalloproteinase-9 and NO are released into the
      coronary sinus blood during angioplasty in coronary patients. METHODS: In 10
      patients with stable angina undergoing elective percutaneous transluminal
      coronary angioplasty of an isolated stenosis of the proximal left anterior
      descending coronary artery, blood was sampled from the coronary sinus at
      baseline, immediately and 1 min after each balloon deflation. Plasma release of
      metalloproteinase-2 and metalloproteinase-9 was assayed by their gelatinolytic
      activity using zymography, while the liberation of NO metabolites was measured by
      high-performance liquid chromatography. RESULTS: Two consecutive balloon
      inflations each of 60 s duration, resulted in an immediate increase (P<0.05) of
      metalloproteinase-9, but not metalloproteinase-2 activity, followed by
      normalization of metalloproteinase-9 levels to the baseline within 1 min. Plasma
      levels of NO metabolites remained unchanged. CONCLUSIONS: Rapid release of
      metalloproteinase-9 after balloon inflation may both contribute to remodeling and
      protect the vascular wall from post-angioplasty thrombosis.

PMID- 14659851
TI  - Genetic variations of matrix metalloproteinase-1 and -3 promoter regions and
      their associations with susceptibility to myocardial infarction in Japanese.
AB  - Matrix metalloproteinases (MMPs) are involved in plaque rupture, which is the
      main pathological cause of myocardial infarction (MI). Recently, several genetic
      studies have demonstrated that MMP-1 1G/2G polymorphism and MMP-3 5A/6A
      polymorphism modify each transcriptional activity in allele specific manners.
      Within this context, we conducted case-control studies to examine whether these
      genetic polymorphisms are associated with susceptibility to MI. Two groups
      comprising patients with MI (group-1 164 patients, group-2 302 patients) were
      compared with control group comprising 335 patients without cardiovascular
      diseases. The MMP-3 5A allele was more frequent in patients with MI than in the
      control subjects (P=0.018 MI group-1, P=0.0059 MI group-2), whereas there was no
      disease association for MMP-1 genotypes. Logistic regression analyses revealed
      that MMP-3 5A/6A polymorphism was associated with susceptibility to MI [odds
      ratio(OR) (95% confidential interval) 1.67 (1.02-2.74); P=0.042, MI group-1; 1.61
      (1.12-2.23); P=0.0095, MI group-2]. Other important findings were that there was
      strong linkage disequilibrium between these polymorphisms, which are located
      closely on chromosome 11q.22, and that the 5A-1G haplotype was a genetic risk
      factor for MI (OR 1.97 P=0.0082, MI group-1 OR 1.51 P=0.017, MI group-2). Taken
      together, the present findings suggest that genetic variations in these MMP genes
      and especially their haplotype may be useful genetic markers for determining
      susceptibility to MI in Japanese.

PMID- 14659852
TI  - Extra-stent vascular remodeling in in-stent restenosis after 188Re-MAG3 radiation
      therapy.
AB  - BACKGROUND: The effect of beta-radiation on extra-stent vascular remodeling in
      patients with in-stent restenosis has not been studied. The correlation between
      the extent of extra-stent plaque proliferation and that of intimal hyperplasia
      (IH) in in-stent restenosis in patients who received beta-radiation therapy as
      well as conventional therapy has also not been studied. METHODS: We evaluated the
      extra-stent remodeling in diffuse in-stent restenosis between a beta-radiation
      therapy patient group (188Re-MAG3, n=50) and a control group (n=9) by applying
      serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and
      follow-up) images were acquired at the follow-up lesion site and were available
      in 44 of 50 patients who received radiation therapy and in seven of nine control
      patients. RESULTS: There was a significant increase of the external elastic
      membrane (EEM) area in both groups: 16.4 +/- 3.3 mm2 post-intervention to 17.1 +/
      3.3 mm2 at follow-up, P=0.001 in the radiation therapy group, and 16.8 +/- 4.0
      mm2 post-intervention to 17.4 +/- 4.1 mm2 at follow-up, P=0.008 in the control
      group. There were no statistically significant differences of the Delta EEM area
      between the two groups: 0.7 +/- 0.4 mm2 in the radiation therapy group vs. 0.6 +/
      0.4 mm2 in the control group, P=0.389. The Delta IH area correlated with the
      Delta EEM area in the control group (r=0.826, P=0.022), but not in the radiation
      therapy group (r=0.016, P=0.919). CONCLUSIONS: The findings of this IVUS study
      were that positive remodeling (increased EEM area) occurred equally in both
      control and irradiated patients with in-stent restenosis. The extent of
      remodeling was directly in proportion to IH in the control group, but no such
      relationship existed in the irradiated patient group.

PMID- 14659853
TI  - Predictors of short-term outcome in acute chest pain without ST-segment
      elevation.
AB  - BACKGROUND: Management of acute chest pain in the emergency room constitutes a
      challenge. METHODS: Seven hundred and one consecutive patients were evaluated by
      clinical history (chest pain score and risk factors), ECG, troponin I and early
      (<24 h) exercise testing in low risk patients (n=165). A composite end-point
      (recurrent unstable angina, acute myocardial infarction or cardiac death) was
      recorded during hospital stay or in ambulatory care settings for patients
      discharged after early exercise testing. RESULTS: The end-point occurred in 122
      patients (17%). Multivariate analysis identified the following predictors: chest
      pain score > or =11 points (OR=1.8, 2-2.8, 95% CI, P=0.007), age > or =68 (OR
      1.6, 1.1-2.4 CI 95%, P=0.03), insulin-dependent diabetes mellitus (OR 1.9, 1.1
      3.4 CI 95%, P=0.02), a history of coronary surgery (OR 3.3, 1.5-7.2 CI 95%,
      P=0.003), ST-segment depression (OR 1.9, 1.2-3.0 CI 95%, P=0.009) and troponin I
      elevation (OR 1.6, 1.1-2.5, CI 95%, P=0.05). ST-segment depression produced a
      high end-point increase (31 vs. 13%, P=0.0001). Troponin I elevation increased
      the risk in the subgroup without ST-segment depression (20 vs. 11%, P=0.006) but
      did not further modify the risk in the subgroup with ST depression (31 vs. 28%,
      ns). Nevertheless, the negative ECG and troponin I subgroup showed a non
      negligible end-point rate (16% when pain score > or =11 or 7% when pain score
      <11, P=0.004). Finally, no patient with a negative exercise test presented events
      compared to 7% of those with a non-negative test (RR=2.5, 2.1-3.1 95% CI,
      P=0.01). CONCLUSIONS: Emergency room evaluation of chest pain should not focus on
      a single parameter; on the contrary, the clinical history, ECG, troponin and
      early exercise testing must be globally analysed.

PMID- 14659854
TI  - Psychological assessments for cardiac rehabilitation patients.
AB  - Psychological and quality of life measures are important in the assessment of
      cardiac rehabilitation (CR) patients and the outcome of treatment. This study
      aimed to assess the utility and sensitivity to change of three simple
      questionnaires in a CR setting. A total of 1403 patients who entered CR over 51
      months were studied. Patients completed questionnaires before and after their
      phase 3 CR program-Hospital Anxiety and Depression (HAD) scale, WONCA/COOP charts
      and an analogue score of wellbeing. The three instruments took about 5.5 min in
      total to complete and 30 s to interpret. There were highly significant reductions
      in mean anxiety score-from 6.04 to 4.67 (P<0.001, 95% CI -1.52 to -1.16) and
      depression from 4.00 to 2.52 (P<0.001, 95% CI -1.62 to -1.29) The mean analogue
      of wellbeing score improved from 7.09 to 8.19 (P<0.001, 95% CI 0.97-1.22 ) There
      were highly significant improvements in five of the six WONCA domains. There were
      significant correlations between improvements in scores from all instruments. The
      sensitivity indices were in the 'good' range for changes in WONCA physical
      fitness domain and subjective well-being score and in the (moderate) range for
      changes in depression, well-being and WONCA overall health. Initial physical
      fitness was significantly correlated with the initial levels of all psychometric
      scores except anxiety and WONCA feelings, but improvements in fitness were not
      correlated with any changes in psychometric scores. The instruments described
      were quick to administer and to interpret and showed sensitivities to change
      superior to those which have been reported for other questionnaires. We believe
      them to be practical tools for use in CR units.

PMID- 14659855
TI  - Evidence of ischemic preconditioning in patients experiencing first non-ST
      segment elevation myocardial infarction (NSTEMI).
AB  - BACKGROUND: Several studies have demonstrated the protective effects of
      preinfarction angina in Q wave myocardial infarction, implicating the role of
      ischemic preconditioning but this role remains uncertain in patients with a
      NSTEMI. Subendocardial viability in NSTEMI patients, is thought to be less
      dependent on collateral circulation and thus more likely to be protected by other
      mechanisms such as preconditioning. METHODS: We have studied prospectively 40
      patients with first NSTEMI and with angiographically proven poor or no collateral
      development and compared two groups; those with versus those without
      preinfarction angina. All in-hospital events, such as recurrent angina,
      congestive heart failure, arrhythmias and reinfarction were recorded. Serum
      markers of myocardial necrosis (CPK, CPK-MB, AST) and discharge QTc values were
      estimated. RESULTS: Preconditioned patients suffered less recurrent angina (18
      vs. 55% P=0.014), congestive heart failure (0 vs. 22%, P=0.02), arrhythmic events
      (0 vs. 27%, P=0.008) and had significant smaller values of mean peak CPK (381 +/-
      152 vs. 859 +/- 496 I.U./l, P=0.0008), mean peak CPK-MB (45.5 +/- 24.6 vs. 105.2
      +/- 87 I.U./l, P=0.01), mean peak AST (59.8 +/- 23.1 vs. 112.4 +/- 64.3 I.U./l,
      P=0.003) and QTc value at discharge (0.42 +/- 0.03 vs. 0.46 +/- 0.05 s, P=0.005)
      than patients without preconditioning. Multiple logistic regression analysis
      confirmed that the absence of preinfarction angina (relative risk 9.10, 95% CI
      2.08-40.00, P=0.003) was a significant predictor of in-hospital complications.
      CONCLUSIONS: Preinfarction angina constitutes a strong clinical correlate to
      ischemic preconditioning in patients with first NSTEMI, offering serious
      protection, by improving in-hospital outcome and reducing infarct size.

PMID- 14659856
TI  - Reduction of ST elevation in repeated coronary occlusion model depends on both
      altered metabolic response and conduction property.
AB  - The aim of this study was to elucidate the mechanisms of altered electrical
      response to ischemia in repeated coronary occlusion model. To test its dependence
      on metabolic response, extracellular K+ concentration (eKC), myocardial pH and
      PCO2 were simultaneously measured with epicardial ECG during three consecutive 4
      min of left anterior descending coronary artery (LAD) occlusion separated by 15
      min of reperfusion in canine hearts. ECG changes induced by infusion of high K+
      buffer (10 mM) into the coronary arterial bed via carotid artery-LAD bypass
      (referred to as high K+-challenges: HKC) were also tested prior to (the first
      HKC), and during each reperfusion period (the second to the fourth HKC). ST
      elevation was significantly reduced in subsequent occlusions (3.14 +/- 0.48 and
      2.98 +/- 0.47 mV in the second and third occlusion, both P<0.05, compared to 4.91
      +/- 0.78 mV in the first). This was accompanied by significant attenuation of the
      changes in eKC, tissue pH and PCO2. ST elevation induced by HKC also
      significantly reduced after repeated occlusion (4.09 +/- 0.79 mV in the fourth
      HKC vs. 5.64 +/- 0.68 mV in the first, P<0.05) in spite of the identical changes
      in eKC during HKC. This progressive decrease in ST changes by HKC was rather
      consistent with augmented conduction delay (86.4 +/- 7.1% increase in activation
      time in the fourth vs. 54.3 +/- 3.4% in the first, P<0.01). These findings
      indicate that repeated ischemia induces altered electrical response to subsequent
      ischemia based on both attenuated metabolic response and altered conduction
      property.

PMID- 14659857
TI  - Fractional shortening-velocity ratio for assessment of aortic stenosis severity
      in patients with systolic dysfunction.
AB  - BACKGROUND: In the study of severity of aortic stenosis many different methods
      derived from transthoracic echocardiography are used. Their principal limitations
      are left ventricular dysfunction and calcified aortic valve. The objective of
      this study was to assess the utility of a described echocardiographic index: the
      fractional shortening-velocity ratio (FSVR=FS/4Vmax2) in those patients with left
      ventricular systolic dysfunction. METHODS: We studied 72 patients with aortic
      stenosis and aortic valvular area (AVA)< or =2 cm2. AVA was assessed by the
      Gorlin equation. Left ventricular systolic dysfunction was defined by FS< or
      =29%. Using receiver operating characteristic curves analysis to test the
      predictive discrimination of patients with and without critical aortic stenosis,
      we studied the best FSVR value to assess aortic stenosis severity. RESULTS: We
      found a significant linear correlation between AVA and FSVR (r=0.59; P<0.001). A
      value of FSVR < or =0.78 allowed the identification of patients with AVA< or =0.8
      cm2 with good sensitivity and specificity (sensitivity: 94.5%; specificity: 60%;
      positive predictive value: 90% and negative predictive value: 75%). In our
      population, 22 patients (32%) showed a systolic dysfunction. The correlation AVA
      FSVR was also significant in this group (r=0.68; P<0.001) and it may be even
      better than in the total group. However, the FSVR with the best sensitivity
      specificity relation was different to the value used in the global group. A FSVR
      value <0.65 showed the best sensitivity-specificity relation in identifying
      patients with severe aortic stenosis (sensitivity: 100% and specificity: 56%).
      CONCLUSION: The FSVR is a very simple and noninvasive index. It allows
      identification of patients with severe aortic stenosis with excellent sensitivity
      and good specificity. It may be useful in the evaluation of patients with aortic
      stenosis and left ventricular dysfunction, although, there is not an accepted
      FSVR value with the best-combined sensitivity-specificity, to identify a critical
      aortic stenosis.

PMID- 14659858
TI  - Post-operative course of coronary artery bypass surgery patients who pre-donate
      autologous blood.
AB  - BACKGROUND: Pre-operative autologous blood donation is used to reduce the need of
      allogeneic blood in patients undergoing coronary bypass surgery operations, but
      it is not clear what impact the blood donation has on the post-operative course
      of these patients. METHODS: We studied the post-operative course of 210 patients
      who pre-donated autologous blood before their coronary bypass operation (donors)
      and of 67 patients who were eligible to pre-donate but did not (controls).
      RESULTS: The clinical variables and the technical operative parameters of the
      patients in the two groups were similar. There was no significant difference
      between the duration of assisted ventilation post-operatively (756 +/- 197 vs.
      802 +/- 395 min; P=0.54) or length of stay in the intensive care unit (1.8 +/-
      1.1 vs. 1.7 +/- 0.9 days; P=0.52) of the two groups. The number of autologous
      units of packed red cells and of fresh frozen plasma (FFP) received by the donors
      was significantly higher than the number of units of allogeneic packed red cells
      (1.5 +/- 0.9 vs. 0.3 +/- 0.9; P=0.001) and the units of homologous FFP received
      by the controls (2.3 +/- 0.8 vs. 0.6 +/- 1; P=0.001). CONCLUSIONS: We found no
      evidence that autologous blood donation exerted a negative influence on the post
      operative course of patients undergoing coronary bypass surgery. Patients who pre
      donated blood received no allogeneic blood products, but the number of autologous
      blood products received by donors was higher than the number of blood products
      received by patients who did not pre-donate.

PMID- 14659859
TI  - Assessment of the effects of various maneuvers on both atrial pressure changes.
AB  - The aim of the present study was to determine which maneuver causes the greatest
      pressure difference between both atria by measuring right and left atrial
      pressures simultaneously after certain maneuvers. Thirty-two coronary care unit
      patients, whom a Swan-Ganz catheter was inserted because of acute left
      ventricular dysfunction, hypotension, sinus tachycardia with unknown cause, were
      included in this study. The basal values of peak right atrium (RA) pressure and
      corresponding pulmonary capillary wedge pressure (PCWP) were measured via two
      separated transducers. Patients were tutored with several trials to perform
      breath holding, successive three strong coughs, Valsalva maneuver, 20 degrees
      head down, respectively. In the end of these maneuvers, the peak RA pressure and
      corresponding PCWP were measured simultaneously. All maneuvers caused an increase
      in RA pressure. The highest peak RA pressure was obtained by means of the
      Valsalva maneuver (7.6 +/- 5 versus 20.4 +/- 7.6 mmHg before and after Valsalva,
      respectively; P<0.001). PCWP (18.8 +/- 5.9 mmHg) increased only with coughing
      (21.2 +/- 6.7 mmHg, P<0.01) and 20 degrees head down maneuver (20 +/- 5.7 mmHg,
      P<0.05). The highest increase in pressure gradient between peak RA pressure and
      corresponding PCWP was observed during Valsalva maneuver (-11 +/- 6.6 vs. 2.3 +/-
      5.9 mmHg, P<0.001). The lowest increase was obtained in 20 degrees head down
      maneuver (-11 +/- 6.6 vs. -8.5 +/- 5.8 mmHg, P<0.001). When measuring the
      pressure of both atria invasively and simultaneously, Valsalva maneuver was the
      most effective maneuver consistent with pressure difference in favour of RA among
      all the other maneuvers.

PMID- 14659860
TI  - In vitro evaluation of vascular endothelial growth factor (VEGF)-eluting stents.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a specific endothelial
      cell mitogen. It promotes re-endothelialisation of the damaged vessel surface
      seen after stenting. Stent thrombosis and in-stent restenosis are partly related
      to endothelial denudation caused by stent implantation. We propose using
      hydrocarbon polymer-coated stents immersed in VEGF to speed re-endothelialisation
      and reduce the risk of stent thrombosis and restenosis. METHODS: Stents (3 x 20
      mm) were immersed in VEGF solutions and maximal VEGF absorption calculated. VEGF
      release from these stents was measured in a perfusion circuit. Delivery of VEGF
      to arterial wall was measured. Sterile VEGF-loaded stents were cultured with
      human umbilical vein endothelial cells. RESULTS: 18.5 +/- 4.1 microg VEGF was
      absorbed, 80% of which was released over 9 days; 11 +/- 6.8% of the initial VEGF
      loaded was delivered to the vessel wall. Cells exposed to VEGF-eluting stents
      showed an 11% increase in growth relative to controls. CONCLUSION: VEGF may be a
      candidate for stent-based delivery and may increase the rate of
      endothelialisation in vivo.

PMID- 14659861
TI  - Coronary artery bypass surgery in octogenarians: outcomes in a tertiary referral
      university hospital in a developing country.
AB  - BACKGROUND: The number of people older than 80 years is increasing worldwide and
      many of these patients are being referred for coronary artery bypass surgery
      (CABG). Several recent reports from the USA and Europe have shown that CABG can
      be performed in octogenarians with an acceptable risk. However, data from
      developing countries regarding this subject is lacking. The objective of this
      study was to analyze the clinical characteristics and in-hospital events of
      octogenarian patients undergoing CABG at a tertiary referral university hospital
      in a developing country. METHODS: The study included 28 consecutive octogenarian
      patients who underwent CABG at the American University of Beirut, between January
      1998 and December 2000. The medical records of these patients were reviewed for
      demographic information, clinical and catheterization findings, operative
      characteristics, and in-hospital events (death, myocardial infarction, and
      stroke). RESULTS: The mean age of the study group was 82 +/- 2 years and 75% were
      males. Seventy-eight percent of the patients had an acute myocardial infarction
      or unstable angina prior to CABG. All of the patients were in NYHA class I or II
      and none of the operations were done on an emergent basis. The mean ejection
      fraction was 48 +/- 7%. Eighty-six percent of patients had multivessel disease
      and four patients had aortic valve replacement (AVR) concomitantly with the CABG.
      The in-hospital mortality was 0%. Three patients (11%) had a post-operative
      myocardial infarction, and one patient (4%) had a stroke. The mean post-operative
      stay was 9 +/- 7 days with only three patients (11%) staying for more than 14
      days. The multivariate predictors of in-hospital cardiovascular events were
      concomitant AVR (P=0.01), and an ejection fraction <40% (P=0.03). CONCLUSION: In
      carefully selected octogenarian patients who are clinically stable in NYHA class
      I or II, and where the operation is not done on an emergent basis, CABG can be
      performed with an acceptable risk and a low in-hospital mortality.

PMID- 14659862
TI  - Gene-gene interaction of PPARgamma and ApoE affects coronary heart disease risk.
AB  - BACKGROUND: Apolipoprotein epsilon4 has been proposed as a genetic predictor for
      CHD. Peroxisome proliferator-activated receptors (PPAR), a recent identified
      nuclear transcription factor, is involved in regulation of many target genes and
      plays an important role in lipid metabolism, insulin sensitivity, obesity and
      atherosclerosis. PPARgamma gene polymorphisms may affect the profile of CHD
      related risk factors. HYPOTHESIS: Interaction between PPARgamma gene polymorphism
      and apoE polymorphisms affect the presence of CHD. METHOD: This is a case-control
      study, which enrolled 150 cases with CHD and 157 controls without CHD. Polymerase
      chain reaction-restricted fragments length polymorphism was used to determine the
      apoE genotype and PPARgamma C161-->T substitution. RESULTS: ApoE epsilon4 allele
      was significantly more prevalent in CHD patients than in controls (13.05 vs.
      7.35%, P<0.05). The apoE epsilon4 carries had significant higher LDL-C levels
      than other apoE carriers and this tendency could be modified by PPARgamma CT
      genotype. ApoE genotype epsilon4 was an independent risk factor for CHD (OR=4.29,
      95%CI: 1.6-11.48, P=0.004). A significant interaction between apoE epsilon4 and
      PPARgamma CT genotype was detected with respect to the effect on CHD (P=0.045).
      CONCLUSION: This is the first study to explore the effect of interaction between
      PPARgamma C161-->T variant and apoE epsilon4 genotype. The result exhibited an
      interaction effect of two genes on serum cholesterol level. The association of
      CHD to apoE genotype was subjected to the attenuation effect of PPARgamma CT
      genotype.

PMID- 14659864
TI  - Acute pulmonary edema after cardioversion of cardiac arrhythmias.
AB  - OBJECTIVE: To examine the occurrence of acute pulmonary edema after cardioversion
      of arrhythmias. METHODS: Cases, case series, and related articles on the subject
      identified through a comprehensive literature search were examined. RESULTS:
      Thirty cases (23 males) of post cardioversion acute pulmonary edema were
      identified. The mean age was 53.8 +/- 13 years (range, 18 to 75 years).
      Underlying arrhythmias were atrial fibrillation (69%), atrial flutter (24%),
      supraventricular tachycardia (4%), and ventricular tachycardia (4%). The duration
      of arrhythmia preceding cardioversion varied widely ranging from 1 day to 13
      years. Twenty-six (87%) patients had concomitant cardiovascular disease
      comprising of coronary artery disease (38%), rheumatic heart disease (23%),
      cardiomyopathy (23%), and hypertension (8%). Direct current electrical
      cardioversion was used in 28 (93%) patients and pacing in two (7%) patients.
      Occurrence of pulmonary edema was independent of the amount of energy used for
      cardioversion (range 20 to 1280 Joules, mean 263 +/- 27 Joules). Short acting
      general anesthetic drugs were administered in 14 (47%) and sedation in eight
      (27%) patients. Sinus rhythm was established in 23 (77%) patients. Duration to
      develop pulmonary edema after cardioversion was available in 23 patients and
      ranged from immediately to 96 h. Pulmonary edema occurred within 15 min after
      cardioversion in 22%, within 3 h in 30%, within 24 h in 30%, within 48 h in 17%
      and within 96 h in remaining 4% of patients. Three patients required mechanical
      ventilation. CONCLUSION: The rare complication of acute pulmonary edema after
      cardioversion has been reported mostly in patients with underlying cardiac
      disease, and is independent of the amount of energy used for cardioversion.

PMID- 14659863
TI  - Safety and tolerability of abciximab in patients with acute myocardial infarction
      and failed thrombolysis.
AB  - AIM: The aim of this study was to evaluate glycoprotein IIb/IIIa receptor
      inhibitor effectiveness in AMI patients with unsuccessful thrombolysis. METHODS:
      Eighty-four patients hospitalised within 4 h of symptom onset were randomised
      (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa
      inhibitors were administered to patients who did not present with reperfusion
      signs 30 min after starting thrombolysis and 30-60 min after the end of full
      thrombolysis in patients with pain recurrence and ST-segment elevation.
      Reperfusion was assessed by the creatine kinase peak occurring within 12 h, by
      the observation of rapid ST-segment reduction (50-70% within 1 h) in 12-lead ECG
      continuous monitoring, by the rapid regression of pain and by the development of
      early ventricular arrhythmias. Group 1 (GP IIb/IIIa) (42 patients) received
      treatment with GP IIb/IIIa inhibitors i.v., heparin according to TIMI-14 trial
      and aspirin during failed thrombolysis or after 30-60 min effective thrombolysis
      because of pain recurrence and ST segment elevation. Group 2 (placebo) (42
      patients) received a full dose of rtpA (100 mg) and placebo either during failed
      thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence
      and ST segment elevation and standard heparin treatment and aspirin. RESULTS:
      Thirty-nine group 1 (GP IIb/IIIa) patients showed rapid reperfusion (6 +/- 4 min)
      after abciximab treatment; 22 patients received rtpA 65 mg and 20 patients
      received rtpA 100 mg and subsequent GP IIb/IIIa inhibitor treatment.
      Coronarography, performed after 3-12 h, showed patency of infarct related artery
      (IRA) in 39 patients whose clinical picture was suggestive of rapid reperfusion
      during administration of a bolus of GP IIb/IIIa inhibitors. No group 2 (placebo)
      patients showed reperfusion and they were submitted to rescue PTCA. SIDE EFFECTS:
      Four cases in the GP IIb/IIIa group and two cases in placebo group (major
      bleeding). Patients receiving GIIb/IIIa inhibitors showed a reduced incidence of
      stent treatment (ns) and a significant reduction of events (angina) within 30
      days of treatment. CONCLUSION: Our data suggest the possibility of using IIb/IIIa
      glycoprotein receptor inhibitors in patients with AMI and failed thrombolysis.
      The increased risk of bleeding was acceptable. The most important results were
      the safety of this combination.

PMID- 14659865
TI  - Ad hoc transradial coronary angioplasty strategy: experience and results in a
      single centre.
AB  - BACKGROUND: The combination of diagnostic and angioplasty as a single procedure
      is becoming common practice in many institutions, but the feasibility of this
      strategy performed with the transradial approach in a large group of patients has
      not been evaluated. This study was performed to explore the feasibility, safety
      and cost-effectiveness of the transradial approach as a single procedure for
      diagnostic angiography and angioplasty, including stent implantation. METHODS:
      From February 1999 and November 2000 the percutaneous transradial approach was
      attempted in 800 patients with functional radial arch attested using Allen's
      test. Interventional procedures, PTCA and stent implantation, when indicated and
      appropriated, have been performed as a single procedure. RESULTS: Out of 800
      patients submitted to coronarography, 390 were treated with PTCA and or stent
      implantation as single procedure. In this group of patients, 425 lesions (1.2
      lesions/patient) were treated. A PTCA was performed in 98 (23.5%) lesions and
      PTCA plus stent implantation were performed in 327 (76.5%) lesions. Procedural
      success was achieved in 419/425 lesions (98.5%) in the radial group and in 98% in
      the staged group. The mean time to place the sheath was longer in the transradial
      group (P<0.01), but the time required to obtain hemostasis was markedly shorter
      in the transradial patients (P<0.01); no differences in fluoroscopy time,
      contrast volume and catheters per case was found. Access site bleeding
      complications were significantly reduced in the radial group (P<0.01) and total
      hospital length of stay was lesser in the radial group (mean days 1.9) as
      compared to femoral group (mean days 2.9) with a reduction of total hospital
      charge. The reduction of costs for 100 patients was Euro 78,000. CONCLUSION: Our
      results show that a combined strategy of angiography and angioplasty via the
      radial artery is feasible, safe, more comfortable for the patient, and more cost
      effective than a staged procedure. This approach might be ideal for outpatient or
      ad hoc invasive coronary procedures.

PMID- 14659866
TI  - The use of a distal occlusion balloon protection device in acute coronary
      syndrome.
AB  - We report our early experience in using the PercuSurge GuardWire Plus system as a
      distal protection device in patients with acute coronary syndrome and acute
      myocardial infarction. Forty-three patients received percutaneous coronary
      intervention with the GuardWire Plus system. Thirteen had unstable angina, five
      had non-Q myocardial infarction and 25 had ST segment elevation myocardial
      infarction. Forty-one target lesions were in native coronary vessels and two were
      in saphenous vein grafts. Total occlusion occurred in 18 patients. The mean
      occlusion time by the distal protective balloon was 262.8 +/- 114.1 s.
      Preoperatively, TIMI 0 flow was present in 18, TIMI II flow in two and TIMI III
      flow in 23 patients. Post-operatively, TIMI II and TIMI III flow were established
      in two and 41 patients, respectively. All procedures were successful and the
      GuardWire Plus system was successfully deployed in all but two patients. There
      was no procedure-related major adverse clinical event. There was no major adverse
      clinical event at 30 days. There was no device-related complication. We believe
      that the GuardWire Plus system is safe and feasible in patients with acute
      coronary syndrome and acute myocardial infarction.

PMID- 14659867
TI  - Cardiac troponin T and I and creatine kinase-MB as markers of myocardial injury
      and predictors of outcome following percutaneous coronary intervention.
AB  - AIMS: This study was performed to determine the most sensitive biochemical marker
      for the detection of cardiac myocyte damage potentially sustained during
      percutaneous coronary intervention (PCI) and to assess whether such a marker can
      be used to identify patients at increased risk of poor subsequent clinical
      outcome. METHODS AND RESULTS: We studied 109 consecutive patients presenting with
      clinical stable and unstable angina and undergoing PCI at our institution. Blood
      was sampled for creatine kinase-MB (CK-MB), cardiac Troponin T (cTnT) and I
      (cTnI) immediately before and at 6, 14 and 24 h post-PCI. Five patients with
      raised cardiac markers pre-PCI were excluded from further analysis. The
      occurrence of major adverse cardiac events (MACE) was documented in-hospital, at
      30 days and at long-term clinical follow up of up to 20 months. MACE occurred in
      26/109 (24%) patients: death=1, QWMI=4, NQWMI=5, repeat PCI=16 (nine target
      vessel revascularisations and seven de-novo lesions), CABG=5. cTnI had the
      highest detection rate for myocardial damage, with 58 cTnI-positive patients, 38
      cTnT-positive patients and 28 CK-MB-positive patients in the 24 h following PCI
      (Pearson's Chi square test, P<0.01). The type of interventional strategy per se
      was not significantly associated with post-procedural cardiac marker
      concentrations (Kruskal-Wallis ANOVA, P>0.05). There was a significant
      association between post-procedural cardiac marker concentrations of CK-MB, cTnT
      and cTnI and the occurrence of procedural angiographic complications (P=0.0003,
      0.0002, 0.001, respectively). All three markers, at each sampling time point
      between 6 and 24 h post-PCI, showed a significant predictive relationship with
      MACE in-hospital and at long-term follow up (ROC curve AUC analysis, P<0.05). All
      three markers provided equally predictive information at each of the three post
      procedural sampling time points between 6 and 24 h following PCI. All levels of
      cardiac marker elevation above the clinically discriminant cut-off values were
      significantly predictive of outcome at long-term follow up. CONCLUSIONS: cTnI
      proved to be the most sensitive marker in detecting myocardial necrosis following
      PCI. CK-MB, cTnT and cTnI all provided similarly reliable prognostic information,
      with cTnT and cTnI being marginally superior in predicting MACE at follow up.

PMID- 14659868
TI  - Carcinoid tumor with carcinoid heart disease: the rare case of Hedinger syndrome
      without hepatic metastases.

PMID- 14659869
TI  - Transcatheter balloon closure of post-myocardial infarction ventricular septal
      defect: a bridge to surgery.

PMID- 14659870
TI  - Fluttering waves in electrocardiograms recorded in neonatal intensive care unit.

PMID- 14659871
TI  - Different effects of losartan and delapril on plasma PAI-1 levels in patients
      with mild to moderate hypertension.

PMID- 14659872
TI  - Origin of left main and right coronary arteries from right aortic sinus of
      Valsalva.
AB  - Coronary anomalies may be a part of complex congenital malformations of the heart
      or be an isolated defect. Anomalous coronary arteries are associated with a
      higher incidence of congenital heart diseases, but do not appear to be associated
      with an increased risk for development of coronary atherosclerosis. Coronary
      anomalies are recognized readily on angiography. Unexpected findings during
      invasive procedures would suggest a possibly existing coronary anomaly,
      especially when main branches cannot be opacified by selective contrast medium
      injection. This case report illustrates the clinical and angiographic findings of
      a patient undergoing coronary angiography for evaluation of ischemic heart
      disease with an unexpected presence of anomalous origin of the left coronary
      artery from the right aortic sinus.

PMID- 14659874
TI  - The telomeric protein Rap1 is conserved in vertebrates and is expressed from a
      bidirectional promoter positioned between the Rap1 and KARS genes.
AB  - We have identified the chicken homolog of the mammalian telomere protein
      repression and activation protein 1 (Rap1). Although cRap1 has only 36% sequence
      identity to hRap1, it contains the same conserved BRCA1 C-terminal (BRCT), Myb
      and Rap C-terminus (RCT) domains. Two-hybrid analysis and immunolocalization
      experiments revealed that cRap1 interacts with the telomere-binding protein
      telomeric repeat binding factor (TRF)2 and localizes to telomeres. Thus, despite
      considerable sequence divergence, the identity and overall domain structure of
      telomere-associated proteins is conserved in vertebrates. Analysis of the cRap1
      genomic locus revealed that the cRap1 gene lies immediately adjacent to the cKARS
      (lysyl-tRNA synthetase) gene with the two genes in a head-to-head orientation
      separated by only 57 nt. This same organization is conserved at the human Rap1
      KARS locus. When 5' regions of the cRap1 and cKARS genes were tested for promoter
      activity, the promoters of both genes were found to lie in or near the intergenic
      spacer. The two promoters lack TATA boxes but appear to have downstream promoter
      elements (DPEs). Analysis of human Rap1 and KARS expressed sequence tags (ESTs)
      indicated that this localization of TATA-less promoters to the intergenic spacer
      is a conserved feature of the Rap1-KARS locus.

PMID- 14659875
TI  - Isolation of the mouse Tsll1 and Tsll2 genes, orthologues of the human TSLC1-like
      genes 1 and 2 (TSLL1 and TSLL2).
AB  - We have recently identified the human TSLL1 and TSLL2 genes, which are highly
      homologous to the human lung tumor suppressor gene, TSLC1. Loss of expression of
      the TSLL1 or TSLL2 in several cancers suggests that these genes could also act as
      tumor suppressors. Here, we report the isolation of the mouse orthologous genes,
      Tsll1 and Tsll2. The Tsll1 and Tsll2 cDNAs contain a single open reading frame of
      1188 and 1164 bp encoding a putative immunoglobulin-like cell adhesion molecules
      of 396 and 388 amino acids, which display 95% and 98% identity with those of
      human TSLL1 and TSLL2, respectively. The Tsll1 and Tsll2 genes are both composed
      of nine exons and mapped on mouse chromosome 1q H2-H4 and on 7q A3-B2,
      respectively, both of which conserve syntenies with human chromosomes 1q and 19q.
      Like the human TSLL1, the mouse Tsll1 was expressed exclusively in the brain and
      neurogenic cells, while Tsll1 expression was lost in one of four rodent
      neuroblastoma cell lines. Tsll2 was expressed in the brain and several organs
      including the kidney and liver, whereas loss of Tsll2 expression was detected in
      some rodent cancer cells derived from these tissues. Furthermore, both murine
      TSLL1 and TSLL2 proteins were expressed on the plasma membrane, especially at the
      cell-cell attached site. These data, together with their strong conservation
      during the vertebrate evolution, suggest that TSLL1and TSLL2 could play an
      important role in cell-cell interaction as well as in tumor suppression.

PMID- 14659876
TI  - Specific and conserved roles of TAp73 during zebrafish development.
AB  - p53, p63 and p73 are related transcription factors involved in the regulation of
      cell proliferation, survival and differentiation. Here, we report the isolation
      and characterization of p73 from zebrafish. While for zebrafish p63 only N
      terminally truncated isoforms (DeltaNp63) have been reported, p73 appears to be
      predominantly or exclusively present in transactivating isoforms (TAp73). p73
      shows a very restricted expression pattern during zebrafish development.
      Transcripts are found in a subset of cells of the olfactory system, the
      telencephalon, the dorsal diencephalon, and the pronephric ducts. In addition,
      p73 is expressed in differentiating slow muscle cells of the somites, and in the
      pharyngeal endoderm. We carried out TAp73 gain- and loss-of-function experiments,
      injecting either TAp73alpha mRNA, or antisense morpholino oligonucleotides to
      suppress translation of TAp73 transcripts. The overexpression studies indicate
      that in contrast to p53, TAp73alpha has no pro-apoptotic effect in zebrafish
      embryos. However, TAp73 appears to be required for specific processes during the
      development of the olfactory system, the telencephalon and the pharyngeal arches.
      Together, our data point to both conserved and class-specific roles of p73 during
      vertebrate development.

PMID- 14659877
TI  - Sp and GATA factors are critical for Apolipoprotein AI downstream enhancer
      activity in human HepG2 cells.
AB  - The factors that bind to the hepatic-specific human apolipoprotein AI (apoAI) 48
      bp downstream enhancer (DSE) were identified and characterized by electrophoretic
      mobility shift assays. A significant homology was shown between the histone 4
      (H4) promoters and the hepatic-specific human apoAI DSE at Sp1 and H4TF2 binding
      sites. Human HepG2 nuclear extracts were used to form four specific complexes
      with the DSE (referred to as apoAI DSE-1, -2, -3, and -4). The apoAI DSE-1 and -2
      complexes showed similar binding specificity to the Sp/H4TF1 consensus site
      within the apoAI DSE. The apoAI DSE-1 complex was predominantly recognized by
      anti-Sp1 and Sp3 sera in gel shift assays, indicating that the DSE was recognized
      by multiple Sp family members. Nuclear extracts that were prepared from retinoic
      acid treated HepG2 cells showed increased levels of Sp factors in gel shift and
      Western blot assays. The apoAI DSE-2 complex was identified as H4TF1 and formed
      in the absence of magnesium chloride. The apoAI DSE-3 complex bound to a
      consensus GATA element within the DSE that was recognized by recombinant human
      GATA-6 as well. The apoAI DSE-3 complex was completely disrupted by a GATA-4
      antibody in EMSA. GATA-4 and -6 were detected in nuclear extracts prepared from
      retinoic acid treated HepG2 cells using Western blot assays. The highest apoAI
      DSE-3 levels were observed with retinoic acid treated HepG2 cell nuclear extracts
      in EMSA. ApoAI DSE-4 is a multi-factor complex that includes an Sp/H4TF1 factor
      and either H4TF2 or apoAI DSE-3. Because apoAI DSE mutations revealed
      transcription defects in transient transfection assays, we conclude that the
      entire DSE sequence is required for full apoAI transcriptional activity in HepG2
      cells.

PMID- 14659878
TI  - Functional characterization of CaCBF1, the Candida albicans homolog of centromere
      binding factor 1.
AB  - The centromere binding factor 1 (Cbf1) is necessary for proper chromosome
      segregation and transcriptional activation of methionine biosynthesis genes in
      the yeast Saccharomyces cerevisiae and is essential for viability in the related
      yeasts Kluyveromyces lactis and Candida glabrata. To study the function of Cbf1p
      in Candida albicans, the major human fungal pathogen, we constructed strains in
      which both alleles of the CaCBF1 gene were deleted. The Deltacbf1 mutants
      exhibited a slow growth phenotype and were temperature-sensitive at 42 degrees C.
      In addition, the mutants were auxotrophic for sulfur amino acids and could grow
      on minimal medium only when it was supplemented with either methionine or
      cysteine, suggesting that CaCBF1 is necessary for the expression of genes
      involved in assimilation of inorganic sulfate. Deletion of CaCBF1 also resulted
      in morphological abnormalities, many cells being unusually large. All mutant
      phenotypes were complemented by reintroduction of a functional CaCBF1 copy. The
      Deltacbf1 mutants neither showed enhanced sensitivity to the microtubule
      destabilizing agent thiabendazole nor did they exhibit an increased frequency of
      chromosome loss. These results suggest that Cbf1p is not necessary for efficient
      chromosome segregation in C. albicans.

PMID- 14659879
TI  - Identification, molecular characterization and expression of the gene encoding
      the epidermal growth factor receptor orthologue from the fox-tapeworm
      Echinococcus multilocularis.
AB  - Receptor tyrosine kinases (RTKs) are crucially involved in the development of
      metazoan organisms and possible mediators of cell-cell communication that occurs
      between eukaryotic parasites and hosts. We have now cloned and characterized the
      complete complementary DNA (cDNA) molecule encoding a novel receptor tyrosine
      kinase, EmER, of the human parasite Echinococcus multilocularis. EmER shared
      significant amino acid sequence homologies with members of the epidermal growth
      factor (EGF) receptor family of different phylogenetic origin, exhibited a domain
      structure which is typical for this group of membrane receptors and contained all
      catalytically important residues at the corresponding positions. Highest
      homologies were detected between EmER and a previously identified receptor
      kinase, SER, from the parasitic trematode Schistosoma mansoni. The EmER encoding
      gene, emer, spans a chromosomal region of 39 kb and is composed of 23 exons.
      Structural comparisons indicated that emer and the EGF receptor encoding genes
      from mammals derive from a common ancestor. DNA/DNA hybridization experiments
      demonstrated that emer is present as a single copy locus in the parasite.
      Transcriptional analyses on in vitro cultivated parasite larvae revealed that
      emer is expressed in both the metacestode and the protoscolex stage, although
      about 10-fold higher transcription levels were detectable for the protoscolex.
      Northern blot experiments further indicated that emer is expressed as a single
      5.2-kb transcript in parasitic larvae during an infection of the intermediate
      host. These results suggest an involvement of EmER in echinococcal
      differentiation processes towards the protoscolex stage during natural infections
      and provide, for the first time, structural information on an epidermal growth
      factor receptor-like kinase from a cestode.

PMID- 14659880
TI  - Regulating gene expression using self-inactivating lentiviral vectors containing
      the mifepristone-inducible system.
AB  - Methods to regulate gene expression in vitro and in vivo are currently areas of
      intense research. The present study, therefore, was designed to determine the
      efficacy of transgene expression using the GeneSwitch mifepristone-regulatable
      system within the context of an integrating HIV-1 vector. Lentiviral transfer
      plasmids expressing the red (DsRed2) and green fluorescent protein (EGFP) markers
      were constructed for in vitro assessment on the basal and mifepristone-induced
      cell activation levels by FACS analyses. In our design, efficient cell activation
      and transgene expression were found using a binary lentivector system i.e., the
      trans-activator, Switch, and the inducible promoter-transgene expression cassette
      were cloned into separate vectors. Note that the Switch trans-activator performed
      optimally when cloned into the reverse-orientation, but the inducible promoter
      containing lentivector did not appear to be dependent upon the orientation within
      the lentivector backbone. This binary lentivector system resulted in tightly
      regulated transgene expression, with low basal cell activation in the absence of
      mifepristone (MFP). Upon induction, a 41- to 275-fold increase in the number of
      DsRed2- and EGFP-positive cells were detected (n=3). To determine the inducing
      ability of the GeneSwitch, we cloned the human alpha(1)-antitrypsin cDNA into the
      optimal lentiviral vector and transduced HeLa and Huh7 cells at increasing
      lentivector doses as determined by p24 Gag ELISA. We found that MFP could induce
      the expression of hAAT protein in HeLa cells from 310 to 15,000 ng hAAT/10(6)
      cells/24 h, which was a 48-fold induction. Similar results were observed in huH7
      cells. In all, this study demonstrates that the GeneSwitch system can be designed
      within the context of a lentiviral vector for in vitro gene transfer, and this
      may also provide a viable method for temporally regulating gene expression for
      therapeutic applications in vivo or ex vivo.

PMID- 14659881
TI  - Molecular cloning of a putative Ciona intestinalis cionin receptor, a new member
      of the CCK/gastrin receptor family.
AB  - Cionin, a peptide showing similarities with cholecystokinin and gastrin has been
      shown to be expressed in the gut and neural ganglion of the protochordate Ciona
      intestinalis. The present report describes the cloning of a putative cionin
      receptor (CioR), a new member of the CCK/gastrin family from the gastrointestinal
      tract of C. intestinalis. mRNA from the stomach of C. intestinalis was isolated
      using a modified RNA extraction procedure and, subsequently, reverse-transcribed
      into single-stranded cDNA by means of rapid amplification of 5'- and 3'-cDNA ends
      (RACE-PCR), followed by full-length PCR amplification. The cloned full-length PCR
      amplicons contained a short upstream open-reading frame (uORF) coding for a
      putative 16 amino acid long peptide, followed by a long open reading frame
      encoding a 526 amino acid putative CioR protein. At the amino acid level, the
      putative CioR protein shared 35-40% homology with cloned mammalian, chicken, and
      Xenopus laevis CCK receptors. Phylogenetic analysis revealed that the chicken and
      X. laevis CCK receptors are orthologues of the mammalian CCK2 receptors whereas
      CioR protein forms a clade with vertebrate cholecystokinin receptors. Moreover,
      we found that the CioR cDNA and deduced amino acid sequences were found to
      correspond to the annotated CCK/gastrin-like receptor gene on Scaffold 117 (C.
      intestinalis draft genome project, Joint Genome Institute database;
      http://www.jgi.doe.gov).

PMID- 14659882
TI  - Specific alternative HOX11 transcripts are expressed in paediatric neural tumours
      and T-cell acute lymphoblastic leukaemia.
AB  - HOX11 is a proto-oncogene, which is silent in normal mature T-cells, while being
      aberrantly activated in T-cell acute lymphoblastic leukaemia (T-ALL) by
      translocations t(10;14)(q24;q11) or t(7;10)(q35;q24). Although many oncogenes are
      expressed in alternative forms in cancer, thus far, only one form of the human
      HOX11 transcript has been reported. We describe here the identification of three
      alternative transcripts of the HOX11 proto-oncogene, expressed in primary T-ALL
      specimens. Using rapid amplification of cDNA ends (RACE) and targeted RT-PCR, we
      have sequenced 23 individual cDNA clones characterising these novel transcripts.
      Northern hybridisation identified particular novel exons expressed in T-ALL,
      which are not expressed in normal T-cells. To date, aberrant expression of HOX11
      has only been associated with leukaemia. Our survey of a range of neuroblastoma
      and primitive neuroectodermal tumour (PNET) cell lines demonstrated the
      expression of these novel HOX11 transcripts in tumours of neural origin, while
      their expression was not detected in normal brain tissues. Strikingly, the
      dominant transcript in these neural tumour cell lines is more than 1 kb larger
      than the dominant transcript in T-ALL. These observations, combined with sequence
      data from several EST clones derived from medulloblastoma cDNA libraries, support
      a new hypothesis that HOX11 may also function as a neural oncogene or brain
      tumour marker.

PMID- 14659883
TI  - Evolutionarily conserved cytoprotection provided by Bax Inhibitor-1 homologs from
      animals, plants, and yeast.
AB  - Programmed cell death (PCD) plays important roles in the development and
      physiology of both animals and plants, but it is unclear whether similar
      mechanisms are employed. Bax Inhibitor-1 (BI-1) is an intracellular multi
      membrane-spanning protein and cell death inhibitor, originally identified by a
      function-based screen for mammalian cDNAs capable of suppressing cell death in
      yeast engineered to ectopically express the pro-apoptotic protein Bax. Using this
      yeast assay, we screened expression libraries for cDNAs from the plant,
      Lycopersicon esculentum (tomato), and the invertebrate animal Drosophila
      melanogaster (fruit fly), identifying close homologs of BI-1 as Bax-suppressors.
      We studied the fly and tomato homologs of BI-1, as well as BI-1 homologs
      identified in Arabidopsis thaliana, Oryza sativa (rice), and Saccharomyces
      cerevisiae (budding yeast). All eukaryotic homologs of BI-1 blocked Bax-induced
      cell death when expressed in yeast. Eukaryotic BI-1 homologs also partially
      rescued yeast from cell death induced by oxidative stress (H(2)O(2)) and heat
      shock. Deletion of a C-terminal domain from BI-1 homologs abrogated their
      cytoprotective function in yeast, demonstrating conserved structure-function
      relations among these proteins. Expression of tomato BI-1 by agroinfiltration of
      intact plant leaves provided protection from damage induced by heat-shock and
      cold-shock stress. Altogether, these findings indicate that BI-1 homologs exist
      in multiple eukaryotic species, providing cytoprotection against diverse stimuli,
      thus implying that BI-1 regulates evolutionary conserved mechanisms of stress
      resistance that are germane to both plants and animals.

PMID- 14659884
TI  - A unifying model for functional difference and redundancy of presenilin-1 and -2
      in cell apoptosis and differentiation.
AB  - Mutations in genes encoding the highly homologous proteins presenilin-1 and -2
      (PS1 and PS2) are linked to the early onset of Alzheimer's disease (AD). Here, we
      report that polyclonal antibodies against Xenopus PSbeta (PS2), but not PSalpha
      (PS1), suppress the in vitro apoptotic activation of Xenopus egg extracts. To
      clarify the relationship between structural and functional differences in
      presenilins, we searched for presenilin homologues in various living sources, and
      found that presenilins were divided into three distinct groups, named alpha-,
      beta- and gamma-types, based on the size of the large hydrophilic loop (HL)
      regions as follows: HLalpha/HLbeta/HLgamma=4:3:6. No such size conservations were
      found in the N-terminal (NT) hydrophilic regions. Phylogenetic studies revealed
      that the presenilin genes were duplicated independently in different lineages of
      phyla/divisions, suggesting that there were functional requirements for and
      constraints on the generation and conservation of these HL sizes. On the basis of
      these findings, we propose a model postulating that both PS1 and PS2 can be
      differentiative or apoptotic when they are proteolytically processed within the
      HL regions or not, respectively, and PS1 may be more sensitive than PS2 to auto
      proteolytic cleavage due to the larger size of the HL region of the former.
      Furthermore, the model assumes that C-terminal fragments (CTF) stabilized by
      phosphorylation may inhibit both the activities due to the dominant-negative
      effect. The model explains not only the functional redundancy but also apparently
      conflicting observations reported so far for PS1 and PS2.

PMID- 14659885
TI  - Transcriptional regulation and mutational analysis of a dctA gene encoding an
      organic acid transporter protein from Pseudomonas chlororaphis O6.
AB  - A dctA gene encoding a protein with identity to a C(4)-dicarboxylic acid/H(+)
      symporter was cloned from a beneficial root colonizer, Pseudomonas chlororaphis
      O6 (PcO6). Expression of the dctA gene was induced in minimal medium by several
      organic acids and was repressed by glucose. Highest expression was observed in
      early-logarithmic (log) cells grown on fumarate, acetate or succinate with
      decline as cells approached late-log growth phase. The dctA transcript
      accumulated weakly when cells were grown on malate, but strong expression was
      observed with benzoate. Expression of the dctA transcript was repressed in early
      log cells upon addition of glucose to fumarate, but was detected as the cell
      culture aged. A dctA-deficient mutant of PcO6, constructed by marker exchange
      mutagenesis, did not grow on minimal medium containing succinate, benzoate,
      acetate or fumarate and growth on malate was delayed. The dctA mutant and wild
      type grew equally on citrate, glucose, fructose, sucrose or inositol. We conclude
      that the transporter protein encoded by dctA is essential for utilization of
      certain organic acids and its expression is controlled by the availability of
      sugars.

PMID- 14659886
TI  - The mouse zinc-fingers and homeoboxes (ZHX) family; ZHX2 forms a heterodimer with
      ZHX3.
AB  - Human zinc-fingers and homeoboxes (ZHX) 1, ZHX2 and ZHX3, members of the ZHX
      family, contain two Cys(2)-His(2)-type zinc-finger motifs and five homeodomains
      (HDs). These proteins not only form homodimers but heterodimers with ZHX1 as well
      and act as ubiquitous transcriptional repressors. The cloning of mouse ZHX2 and
      ZHX3 cDNAs and the corresponding genes from a 129 mouse genomic library are
      reported, along with an analysis of the heterodimerization of ZHX2 with ZHX3. The
      mouse ZHX2 and ZHX3 proteins consist of 836 and 951 amino acid residues,
      respectively. The similarity of amino acid sequences of each protein with those
      of human orthologue is 87.0% and 85.2%, respectively. An analysis of genomic
      clones revealed that an entire coding sequence and a portion of the 5'- and 3'
      noncoding sequence of mouse ZHX2 cDNA are encoded by a single exon of the mouse
      ZHX2 gene as well as the mouse ZHX1 gene. In contrast, in the case of the mouse
      ZHX3 gene, the coding sequences of ZHX3 cDNA are separated by an intron. A 4.5-kb
      ZHX2 transcript, and three ZHX3 transcripts, 9.5-, 6.5- and 4.4-kb, are
      ubiquitously expressed, although their levels vary. Lastly, in vitro and in vivo
      protein-protein interaction assays revealed that ZHX2 is able to form a
      heterodimer with ZHX3 via a region containing each HD1.

PMID- 14659887
TI  - Identification of NAD+-dependent isocitrate dehydrogenase 3 gamma-like (IDH3GL)
      gene and its genetic polymorphisms.
AB  - We have identified a novel human gene designated as IDH3GL (isocitrate
      dehydrogenase 3 gamma-like) that is expressed specifically in human testis. The
      gene corresponds in sequence to an EST (expressed sequence tag) A1476435 that was
      first detected by differential expression analysis using a microarray assay. The
      full-length cDNA sequence (1037 bp) was isolated from the human testis 5'-3'-RACE
      cDNA libraries and found to have 83% nucleotide sequence identity with part of
      the IDH3G (isocitrate dehydrogenase 3 gamma). The IDH3GL gene consists of 3 exons
      spanning approximately 220 kb within the region of the NELL1 gene on chromosome
      11p15.1. Sequence analysis of the IDH3GL cDNA revealed the presence of a
      premature stop codon at nucleotide positions 337-339 that results in a truncated
      peptide with 112 amino acids. This stop codon is conserved in various human
      ethnic populations and in the chimpanzee (Pan troglodytes). In order to assess
      the functional status of IDH3GL, especially in relation to the presence of the
      putative premature stop codon, single nucleotide polymorphisms (SNPs) were
      screened in the upstream, coding and non-coding regions of the IDH3GL gene in a
      Japanese population. As a result, a total of 10 SNPs were identified, seven were
      novel and one of them was a non-synonymous amino acid substitution from Leu to
      Val. We conclude that the IDH3GL gene sequence is a splice variant of the NELL1
      gene and that it probably evolved from a transposed pseudogene of the IDH3 gene.

PMID- 14659888
TI  - Cloning, characterization, and expression of the rat relaxin gene.
AB  - Relaxin, a hormone in the insulin superfamily, is synthesized by the corpus
      luteum of the rat ovary. Expression of relaxin precursor mRNA in rats is sharply
      induced after day 10 of pregnancy and plateaus on days 15 to 20 (parturition
      occurs on day 23). In an effort to understand this induction, we cloned the gene
      and carried out promoter analyses by transient transfection and chromatin
      immunoprecipitation methods. The single gene is 2.9 kilobases and is composed of
      two exons and one intron. There are alternative splice acceptor sites, 3 base
      pairs apart, which account for the inclusion of an extra codon in about 10% of
      the transcripts. The induction of transcription by day 15 was observed by the
      binding of polymerase II and histone H3 acetylation at the promoter region. There
      is a functional STAT binding site, about 3.8 kb upstream from the transcriptional
      start site, that is occupied by STAT3 on day 6 of pregnancy, when relaxin
      expression is minimal; on day 15, when expression is maximal, STAT3 is replaced
      by STAT5a. These data are consistent with STAT5 playing a role in the induction
      of relaxin expression.

PMID- 14659889
TI  - The rod opsin pigments from two marsupial species, the South American bare-tailed
      woolly opossum and the Australian fat-tailed dunnart.
AB  - Rod visual pigment genes have been studied in a wide range of vertebrates
      including a number of mammalian species. However, no marsupials have yet been
      examined. To correct this omission, we have studied the rod pigments in two
      marsupial species, the nocturnal and frugivorous bare-tailed woolly opossum,
      Caluromys philander, from Central and South America, and the arhythmic and
      insectivorous fat-tailed dunnart, Sminthopsis crassicaudata, from Australia.
      Phylogenetic analysis establishes that the cloned opsin sequences are orthologues
      of rod opsin genes from other vertebrate species. The deduced amino acid
      sequences show that both possess glutamate at residue 122, a feature of rod
      opsins, and the corresponding gene follows the typical vertebrate rod opsin
      pattern of five exons separated by four introns. Compared to other vertebrates, a
      stretch of five residues near the C-terminus is deleted in the rod opsin of both
      marsupials and all eutherian mammals. From microspectrophotometric measurements,
      the pigments in the two species show an 8 nm difference in peak absorbance; the
      molecular basis for this spectral shift is discussed and two candidate
      substitutions are identified.

PMID- 14659890
TI  - Regulation of the FGF-4 gene by a complex distal enhancer that functions in part
      as an enhanceosome.
AB  - The exact mechanisms by which enhancers regulate transcription are currently
      under investigation. For some genes, activation is accomplished by an intricate
      array of enhancer cis-regulatory elements that direct the assembly of a gene
      specific activation complex known as an "enhanceosome". Transcription of the
      fibroblast growth factor-4 (FGF-4) gene during early development is controlled by
      a powerful distal enhancer located 3 kb downstream of the transcription start
      site within the 3' untranslated region of the gene. Previous studies have shown
      that FGF-4 enhancer function is mediated by at least three critical positive cis
      regulatory elements: an HMG, a POU, and a GT-box motif, which bind the
      transcription factors Sox-2, Oct-3, and Sp1/Sp3, respectively. In this study, we
      identify a second essential HMG motif within the FGF-4 enhancer that binds the
      transcription factor Sox-2. Moreover, we demonstrate that spatial alignment of
      the new HMG motif, relative the other enhancer cis-regulatory elements, is
      important. Based on findings presented in this report, and work published
      earlier, we propose that the previously identified core HMG and POU cis
      regulatory elements of the FGF-4 enhancer are dependent on one another and
      function in an enhanceosome-like manner. In contrast, the HMG motif identified in
      this study is only partially dependent on the other enhancer cis-regulatory
      elements for its function.

PMID- 14659891
TI  - An improved growth hormone reporter gene shows a different pattern of
      transactivation by promoter fragments.
AB  - Granulocytic differentiation of myeloid NB4 cells was noted to transactivate the
      genomic human growth hormone (hGH) reporter construct in the absence of a driving
      test promoter. Such spurious hGH transactivation also occurred upon co
      transfection of plasmids expressing the transactivators c-Myb and C/EBPalpha into
      undifferentiated NB4 cells. Modifications to the reporter gene and the vector
      resulted in a reporter construct unaffected by such stimuli. When human
      neutrophil peptide 1 (hnp-1) gene promoter fragments were tested using both the
      original and modified reporter constructs, a clear difference in the pattern of
      transactivation was noted. This suggests that promoter and enhancer elements in
      the reporter construct plasmid DNA can effect the analysis of the test promoter.

PMID- 14659892
TI  - On dynamics of overlapping genes in bacterial genomes.
AB  - A genome-wide computational analysis of overlapping genes in various prokaryotic
      genomes was conducted to study the evolutionary rates of the formation and
      degradation of overlapping genes. Overlapping genes are adjacent genes that
      overlap partially or entirely. Overlapping gene pairs extracted from complete
      bacterial genome sequences were classified into three directional patterns,
      namely, 'convergent' (--><--), 'unidirectional' (-->-->), and 'divergent' (<---
      >). Divergent overlapping genes were rare compared to the other two patterns. We
      also compared the structures of overlapping genes that are not conserved in the
      homologous genes of different species. We found that overlapping genes are mainly
      generated from gene pairs with short intergenic regions. Overlapping genes caused
      by mutations at the 3'-end of genes occur more frequently than overlapping genes
      generated by mutations at the 5'-end of genes in closely related species. In
      contrast, gene overlaps due to mutations at the 5'-ends accumulate in distant
      species. These differences presumably correlate to the genomic divergence among
      species. The evolution of these overlapping gene structures is probably related
      to the evolutionary time scale, which suggests that the evolution of overlapping
      genes occurs at a universal mutation rate across species.

PMID- 14659893
TI  - The TPTE gene family: cellular expression, subcellular localization and
      alternative splicing.
AB  - The human TPTE (Transmembrane Phosphatase with TEnsin homology) gene family
      encodes a PTEN-related tyrosine phosphatase with four potential transmembrane
      domains. Chromosomal mapping revealed multiple copies of the TPTE gene on
      chromosomes 13, 15, 21, 22 and Y. Human chromosomes 13 and 21 copies encode two
      functional proteins, TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase)
      and TPTE, respectively, whereas only one copy of the gene exists in the mouse
      genome. In the present study, we show that TPTE and TPIP proteins are expressed
      in secondary spermatocytes and/or prespermatids. In addition, we report the
      existence of several novel alternatively spliced isoforms of these two proteins
      with variable number of transmembrane domains. The latter has no influence on the
      subcellular localization of these different peptides as shown by co
      immunofluorescence experiments. Finally, we identify another expressed TPTE copy,
      mapping to human chromosome 22, whose transcription appears to be under the
      control of the LTR of human endogenous retrovirus RTVL-H3.

PMID- 14659894
TI  - Enzymatic amplification staining for single cell analysis: applied to in situ
      hybridization.
AB  - Single cell analysis by flow cytometry is a powerful modality for analyzing the
      expression of a set of molecules. Nevertheless, the most significant deficiency
      of this technology has been the poor sensitivity of flow cytometry compared to
      other techniques such as immunoblotting. In order to address this deficiency, we
      have developed an enzymatic amplification system for flow cytometry that enhances
      the specific signal by 10-100-fold. Using enzymatic amplification staining (EAS),
      we and others have been able to assess the expression of molecules that could not
      be detected otherwise. In this review, we show the capability of this new
      technology to detect specific RNA expression.

PMID- 14659895
TI  - Rapid analysis of the Vbeta repertoire of CD4 and CD8 T lymphocytes in whole
      blood.
AB  - Determination of the T cell receptor Vbeta repertoire of human CD4 and CD8
      populations is a useful immunological tool, particularly in the investigation of
      superantigen involvement in various disease states. We describe the optimisation
      of a rapid technique for the simultaneous evaluation of 24 Vbeta families of the
      T cell receptor of CD4 and CD8 positive lymphocytes in whole blood by flow
      cytometry adapting a commercially available monoclonal antibody kit. The
      technique described is reliable and reproducible, and we describe its use as a
      potential diagnostic tool in patients with staphylococcal and streptococcal toxic
      shock syndromes.

PMID- 14659896
TI  - Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by
      sequential antigen panning of a phage display library.
AB  - Identification of broadly cross-reactive human monoclonal antibodies (mAbs) has
      major implications for development of vaccines, inhibitors and research tools.
      Here we describe a sequential antigen panning (SAP) methodology that may
      facilitate the selection of such antibodies. An HIV-specific antibody Fab (m18)
      was selected from a human Fab phage-display library by SAP against several
      recombinant soluble HIV envelope glycoproteins (Envs) and Env-sCD4 complexes.
      This Fab bound to a variety of recombinant soluble Envs (gp140s) from primary HIV
      isolates representing different clades, and inhibited cell fusion and virus entry
      mediated by Envs of primary HIV isolates. The methodology and the results may
      have implications for development of HIV vaccines and inhibitors, as well as for
      identification of antibodies to conserved epitopes on rapidly mutating viruses
      and cells.

PMID- 14659897
TI  - Quantitative cytokine gene expression in human tonsils at excision and during
      histoculture assessed by standardized and calibrated real-time PCR and novel data
      processing.
AB  - Real-time reverse transcription polymerase chain reaction (RT-PCR) assays were
      developed for the quantification of expression of the genes for human interleukin
      (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, IL-15, interferon (IFN)-gamma, tumor
      necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta and for the
      endogenous reference hydroxymethylbilane synthase (HMBS). The assays detected as
      little as five plasmid copies and were 100% specific. The creation and
      integration of a calibration sample into the assays permitted their calibration
      across experiments. To handle the high number of generated data, the correlator
      of advanced real-time assays (CARTA) software was designed to organize samples
      and to automatically control and analyze TaqMan real-time RT-PCR data. The RT-PCR
      assays were applied to quantify levels of cytokine gene expression in human
      palatine tonsils at excision and during 4 days of histoculture. Similar
      longitudinal patterns of cytokine gene expression were observed in all donors,
      but the variations in spontaneous expression levels between donors were large.
      The expression levels in histocultures were constant over time and similar to the
      expression levels at excision except for IL-6 and IL-8, which markedly increased
      following the first 24 h of culture, possibly due to the initial stress. The
      standardized and calibrated RT-PCR assays quantify gene expression of human
      cytokines proved sensitive and specific for the investigation of cell behavior at
      the molecular level and the newly established CARTA software, a reliable tool for
      rapid data handling. Tonsil histocultures could serve as a valuable ex vivo model
      system for further, donor-dependent, studies on activation or repression of
      cytokine gene expression.

PMID- 14659898
TI  - Development of chemiluminescent ELISAs to DDT and its metabolites in food and
      environmental samples.
AB  - Two enzyme-linked immunosorbent assays (ELISA) with chemiluminescent (CL)
      detection for the insecticide DDT and the group of DDT-related compounds have
      been optimized and characterized. Both conjugate-coated ELISAs are based on
      monoclonal antibodies (MAbs) of different specificity and homologous protein
      conjugates. Effects of several physicochemical factors (ionic strength, pH, Tween
      20 and Bovine serum albumin (BSA) concentrations) and solvents (methanol,
      ethanol, acetone and N,N'-dimethylformamide) on the performance of the assays
      were studied and optimized. For the DDT-selective assay, the sensitivity,
      estimated as the I(50) value, was 0.6 microg/l, with a linear working range
      between 0.1 and 2 microg/l and a limit of detection of 0.06 microg/l. For the DDT
      group-selective assay, the sensitivity was 0.2 microg/l, with a linear working
      range between 0.07 and 1 microg/l and a limit of detection of 0.04 microg/l. CL
      ELISAs were four times more sensitive compared to colorimetric ELISAs. Finally,
      both immunoassays were applied to the detection of DDT and group of DDT-related
      compounds in spiked real water, soil and food samples.

PMID- 14659899
TI  - Use of anti-CD3/CD28 mAb coupled magnetic beads permitting subsequent phenotypic
      analysis of activated human T cells by indirect immunofluorescence.
AB  - Functional analysis of T lymphocytes requires in vitro stimulation of these cells
      under experimental conditions that mimic as closely as possible physiological in
      vivo stimulation and that involve antigen/T cell receptor (TCR)-mediated
      activation. Because of the low frequency of antigen-specific T cells in human
      clinical samples, stimulation with a combination of anti-CD3 and anti-CD28
      monoclonal antibodies (mAbs) is a preferred method. Interaction of these mAbs
      with their ligand results in modulation of the mAb-ligand complex from the cell
      surface. However, as a result of incomplete modulation, CD3/CD28 mAb complexes
      often remain at the cell surface, thereby precluding subsequent indirect
      immunofluorescence and flow cytometry analysis using mouse immunoglobulin (Ig)
      specific antibodies. This is of importance in situations in which no specific
      fluorochrome-conjugated mAbs are available, such as in screening procedures of Ig
      containing hybridoma culture supernatants. We propose here the use of CD3/CD28
      mAbs, linked to magnetic beads allowing standardization of the activation
      conditions, optimal activation of T cells and complete modulation of antigen
      antibody complexes from the cell surface.

PMID- 14659900
TI  - Immunological assay for carbohydrate antigen 19-9 using an electrochemical
      immunosensor and antigen immobilization in titania sol-gel matrix.
AB  - We describe a novel electrochemical immunosensor for carbohydrate antigen 19-9
      (CA19-9) based on the immobilization of CA19-9 with titania sol-gel on a graphite
      electrode (GE) by vapor deposition. The CA19-9 membrane was characterized using
      scanning electron microscopy and proved to be chemically clean, porous and
      homogeneous. The incubation of the immunosensor in a solution containing
      horseradish peroxidase (HRP)-labeled CA19-9 antibody led to the binding of HRP
      labeled antibody with the immobilized antigen. The immobilized HRP catalyzed the
      oxidation of catechol by H(2)O(2) and this provided a competitive method for the
      measurement of serum CA19-9. The response current decreased with increasing CA19
      9 concentration in the incubation solution. The effects of pH, amount of HRP
      labeled antibody, incubation time and temperature were explored to provide
      optimum analytical performance. Under optimal conditions, the current decrease of
      the immunosensor was proportional to CA19-9 concentrations in the range of 3-20
      U/ml with a detection limit of 2.68 U/ml at a current decrease of 10%. The
      detection of CA19-9 in two serum samples obtained from clinically diagnosed
      patients with pancreatic carcinoma showed acceptable accuracy. The proposed
      immunosensor provides a new promising tool for the clinical immunoassay of CA19
      9.

PMID- 14659901
TI  - A new epitope tag from hepatitis B virus preS1 for immunodetection, localization
      and affinity purification of recombinant proteins.
AB  - Previously, a murine monoclonal antibody (mAb) KR127 (IgG2a/kappa) that binds
      specifically to the preS1 of hepatitis B virus (HBV) was generated and the fine
      epitope was mapped to amino acids (aa) 37-45 (NSNNPDWDF). In this current study,
      the epitope in combination with KR127 was tested for protein tagging. Initially,
      to evaluate the importance of each residue of the KR127 epitope in antibody
      binding, alanine substitution mutants of the epitope were constructed and
      characterized for KR127 binding by immunoblot analysis and competition ELISA. The
      results showed that substitution of Ser(38) by alanine (S38A) increased the
      affinity to KR127. The mutated epitope (NANNPDWDF), designated S1 tag, was fused
      to the amino (N)- or carboxyl (C)-terminus of three human recombinant proteins,
      soluble B lymphocyte stimulator (sBLyS), the N-terminal domain of thrombopoietin
      (nTPO), and a mitochondrial ribosomal protein (CGI-113) for expression in
      mammalian cells, while it was fused to the N- or C-terminus of two proteins, a
      single-chain antibody fragment (ScFv) and the carboxyl-terminal domain (PAc) of
      the protective antigen of Bacillus anthracis for expression in Escherichia coli.
      The immunodetection, immunoprecipitation, and affinity purification of the
      expressed S1-tagged proteins by KR127 were successfully demonstrated. In
      addition, a KR127 mutant (AP2) with higher affinity, K(d) (0.9 nM), for the S1
      tag compared to that (20 nM) of KR127 was obtained by mutational analysis of the
      heavy chain CDR3 (HCDR3) of KR127. The AP2 antibody was 4-fold more sensitive in
      detecting the S1-tagged protein than KR127. The S1 tag-KR127 or AP2 combination
      could be universally used for monitoring protein expression, localizing proteins,
      and protein purification, as well as studying protein interactions.

PMID- 14659902
TI  - A Fluorospot assay to detect single T lymphocytes simultaneously producing
      multiple cytokines.
AB  - Various subpopulations of T lymphocytes-i.e. Type 1, Type 2, Tr1 T cells-play a
      major role in the homeostasis of the immune system and in the pathogenesis of
      many inflammatory and auto-immune diseases. At present, in the absence of
      specific surface markers, these T cells can only be reliably distinguished on the
      basis of their cytokine production profile. The Elispot assay detects cytokine
      producing cells, but in most cases can detect only one secreted cytokine, which
      represents a major limitation of this technique. We have developed a Fluorospot
      assay to detect single cells that simultaneously produce multiple cytokines. The
      Fluorospot assay permits the detection of regulatory T cells with an
      immunosuppressive activity, identified by their coexpression of IL-10 and
      IFNgamma. Polarized type 1 and type 2 specific tetanus toxoid T cells are also
      directly detected using a dual color Fluorospot. This technique will therefore be
      useful for detailed analysis of T lymphocytes in various disease states in which
      an imbalance of T cell subpopulations is suspected, but will also provide a
      better characterization of polarized specific immune responses.

PMID- 14659903
TI  - Assessment of immunosuppressive drug interactions: inhibition of lymphocyte
      function in peripheral human blood.
AB  - Cyclosporin (CsA) or tacrolimus (TRL) is routinely combined with either sirolimus
      (SRL) or mycophenolate mofetil (MMF) in immunosuppressive regimes in organ
      transplantation. The aim of our study was to establish a specific human blood
      assay of lymphocyte function in order to assess interactions of these drug
      combinations. Different concentrations (10(6)-10(9) nM) of CsA, TRL, SRL or
      mycophenolic acid (MPA, the active metabolite of MMF) was added to whole blood of
      five human volunteers. Drug combinations were studied by adding 250, 500 or 1000
      nM of MPA to different concentrations of CsA, TRL, or SRL or by adding 1, 10 or
      25 nM of SRL to different concentrations of CsA or TRL. After concanavalin-A
      stimulation, whole blood cultures were analyzed by flow cytometry detecting
      lymphocyte proliferation and activation by bivariate expression of proliferating
      cell nuclear antigen (PCNA)/DNA content and T cell-surface activation antigens
      (e.g. CD25, CD95, and CD154). We found an order of potency inhibiting lymphocyte
      function with SRL>TRL>CsA>MPA. In addition, we observed enhanced inhibition of
      PCNA, CD25, CD95 or CD154, if either CsA or TRL was combined with low
      concentrations of MPA, or SRL alone or if SRL was combined with low
      concentrations of MPA. Data analysis revealed an independent functional synergism
      or partial agonism in most combinations. This human blood assay is able to assess
      lymphocyte function and to monitor immunosuppressive therapy. The assay also
      permits pharmacological analysis of drug interactions, which will lead to
      improved safety and therapeutic efficacy in transplanted patients.

PMID- 14659904
TI  - Enzyme-linked immunosorbent assays using immune complexes for the diagnosis of
      tuberculosis.
AB  - The serodiagnosis of tuberculosis has long been the subject of investigation, but
      we still lack a test with widespread clinical utility. The poor sensitivity and
      specificity of commercial assays precludes their use as the sole means of
      diagnosis. All of these assays use mycobacterial antigens adsorbed onto a
      surface. Little attention has been paid to changes in antigen conformation that
      may occur as a result of passive coating of these antigens to solid supports like
      polystyrene. Such changes may cause technical artifacts resulting in false
      positive (FP) and false-negative (FN) reactions. We have developed two different
      enzyme-linked immunosorbent assay (ELISA) systems, in which human serum
      antibodies and target antigens of Mycobacterium tuberculosis are able to
      associate and dissociate freely in solution to form immune complexes. In one
      ELISA, rabbit antibodies against M. tuberculosis, passively coated in the ELISA
      wells, capture the immune complexes (ICs). In the other ELISA, the ICs are
      detected by these same rabbit antibodies but are first captured by passively
      coated goat anti-rabbit IgG. We have compared these two ELISA systems with an
      ELISA using M. tuberculosis antigens passively adsorbed to the solid polystyrene
      surface of the plate. We studied sera from 81 patients with tuberculosis and 47
      healthy subjects. The differences between tuberculosis (TB) patients and healthy
      subjects were statistically significant in all three of our ELISA systems.
      However, the ELISA systems using soluble M. tuberculosis antigens distinguished
      better between TB patients and healthy subjects than the ELISA using surface
      adsorbed M. tuberculosis antigens. We suggest that in the latter ELISA, passive
      adsorption of the target antigens induces conformational change, generating
      altered epitopes that are recognized by antibodies present in the serum from even
      healthy people. These altered conformational epitopes are recognized by
      antibodies that were originally evoked by antigens other than M. tuberculosis,
      known as heterophile antigens.

PMID- 14659905
TI  - A single-chain-Fv-based immunofluorometric assay specific for the CEA variant NCA
      2.
AB  - Carcinoembryonic antigen (CEA) is a member of the immunoglobulin gene
      superfamily. In meconium, a C-terminal truncated form of CEA, denominated NCA-2,
      is predominant. This molecular variant is present also in sera from adult cancer
      patients, but no NCA-2-specific assay is yet available, and its possible clinical
      significance is largely unknown. We have used phage display technology to produce
      a single-chain antibody (scFv) suitable for an NCA-2-specific assay and compared
      the NCA-2 results with CEA values in patient sera. A phagemid library with a
      diversity of 10(7) was constructed from splenic mRNA obtained from a mouse
      immunized with NCA-2 purified from human meconium. Following phage rescue and
      three rounds of panning on solid phases coated with NCA-2, several clones were
      isolated, which displayed high specificity for NCA-2. These were sub-cloned into
      an Escherichia coli expression vector for high-level expression of soluble scFv.
      From BIAcore studies a single scFv with low k(off) and a K(D) of 10(-10) mol/l
      was selected for europium labelling and an immunofluorometric assay with a
      sensitivity of 0.2 microg/l was established. The assay detects a protein in serum
      with a molecular weight significantly lower than CEA. For comparison, a routine
      assay for CEA, which measures both CEA and NCA-2 equivalently, and a CEA-specific
      assay based on the T84.66 antibody were employed. The difference between serum
      values measured with the two CEA assays corresponded to the values determined
      with the NCA-2-specific assay.

PMID- 14659906
TI  - Comparison of the ELISPOT and cytokine flow cytometry assays for the enumeration
      of antigen-specific T cells.
AB  - The enumeration of antigen-specific T cell responses has been greatly facilitated
      in recent years by the development of methods based on the detection of
      cytokines. In particular, the enzyme-linked immunospot (ELISPOT) and cytokine
      flow cytometry (CFC) assays have become popular. Since both assays are likely to
      continue to be in widespread use, it is important to evaluate whether their
      results are comparable. In the current study, we compared the results obtained in
      the ELISPOT and CFC assays using peptide pools corresponding to CMV and HIV-1
      proteins in chronically HIV-1-infected individuals. Analysis of T cell responses
      to peptide pools indicated that the CMV pp65 and HIV-1 Gag CFC and ELISPOT
      derived results were statistically correlated. However, the results obtained with
      each assay differed in important ways: the magnitude of the response was
      consistently higher in the CFC assay while the CFC assay was less likely than the
      ELISPOT assay to detect low-level responses. Furthermore, there was a lack of
      numeric agreement between ELISPOT and CFC results. For studies that require the
      detection of low-level responses, or definition of responses as positive or
      negative, the ELISPOT assay may be preferable. In contrast, the CFC has a greater
      dynamic range and allows for phenotypic discrimination of responding cells,
      making it the assay of choice for most other applications.

PMID- 14659907
TI  - An ELISA serum assay for autoantibodies to HSP70 in immune-mediated hearing loss.
AB  - A Western blot to detect anti-HSP70 autoantibodies has been reported to be of
      diagnostic value for immune-mediated hearing loss patients. While setting up this
      Western blot in our lab, we detected two main problems. First, some patients were
      positive for antibodies to a 70-kDa protein when tested against a whole cell
      lysate, but negative if the antigen used was purified HSP70. Second, if high
      amounts of purified HSP70 were loaded on the gel, both patients and healthy
      controls were positive. We have developed and optimized an ELISA as an
      alternative to the Western blot. This assay is more appropriate to identify
      positive and negative individuals because it is semi-quantitative. The ELISA is
      also more sensitive, requiring very low concentrations of the antigen and thus
      minimizing false positives. Finally, we demonstrated that immune-mediated hearing
      loss patients recognize mainly the native form of HSP70, a fact that potentially
      leads to false negatives when a denaturing Western blot assay is used for
      diagnosis. To test the diagnostic value of the ELISA, we performed a blind test
      with 70 hearing loss patients, as well as 30 healthy controls. A sensitivity of
      84% and a specificity of 93% were obtained, superior to what has been reported so
      far for the Western blot.

PMID- 14659908
TI  - One-tube semi-nested PCR-ELISA for the detection of human cytomegalovirus DNA
      sequences; comparison with hybridization-based and semi-nested-based PCR-ELISA
      procedures.
AB  - Amplification of DNA targets by polymerase chain reaction (PCR) followed by their
      colorimetric detection in an enzyme-linked immunosorbent assay (ELISA) is
      increasingly used in both immunological research and clinical practice. Several
      methods for the labeling and detection of amplified DNA sequences have been
      previously described. In this study, we compared the conventional hybridization
      based PCR-ELISA with a modified semi-nested and one-tube semi-nested PCR-ELISA
      for the detection of human cytomegalovirus (HCMV) DNA. Amplified DNA sequences
      were labeled with biotin and 2,4-dinitrophenyl (DNP), and detected by DNP
      specific monoclonal antibody conjugated to alkaline phosphatase. Using a cloned
      HCMV DNA as a template, we found that the one-tube semi-nested PCR-ELISA gave a
      strong positive response when 20 copies of the template were used, whereas both
      the hybridization-based and the semi-nested-based PCR-ELISA required at least 200
      template copies. The claim of higher sensitivity and robustness of the one-tube
      semi-nested assay was also supported by the analysis of plasma samples from
      patients treated for HCMV infection. Since the modified one-tube semi-nested PCR
      ELISA is quick, sensitive and easy-to-perform, it can be used with advantage in
      routine identification of DNA targets in clinical and other specimens.

PMID- 14659909
TI  - A sensitive method for detecting proliferation of rare autoantigen-specific human
      T cells.
AB  - The ability to measure proliferation of rare antigen-specific T cells among many
      bystanders is critical for the evaluation of cellular immune function in health
      and disease. T-cell proliferation in response to antigen has been measured almost
      exclusively by 3H-thymidine incorporation. This method does not directly identify
      the phenotype of the proliferating cells and is frequently not sufficiently
      sensitive to detect rare autoantigen-specific T cells. To overcome these
      problems, we developed a novel assay for antigen-specific human T-cell
      proliferation. Peripheral blood mononuclear cells (PBMC) were labelled with the
      fluorescent dye 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) and
      cells that proliferated in response to antigen, with resultant reduction in CFSE
      intensity, were measured directly by flow cytometry. This assay was more
      sensitive than 3H-thymidine incorporation and detected the proliferation of rare
      antigen-specific CD4(+) T cells at 10-fold lower antigen concentrations. It also
      allowed the phenotype of the proliferating cells to be directly determined. Using
      the CFSE assay we were able to measure directly the proliferation of human CD4(+)
      T cells from healthy donors in response to the type 1 diabetes autoantigens
      glutamic acid decarboxylase (GAD) and proinsulin (PI).

PMID- 14659910
TI  - Affinity fractionation of lymphocytes using a monolithic cryogel.
AB  - A new type of continuous, supermacroporous, monolithic, cryogel affinity
      adsorbent was developed, allowing specific fractionation and separation of human
      peripheral blood lymphocytes in a chromatographic format. The affinity adsorbent
      was used to design a novel cell separation strategy, which was based on the
      interaction of protein A from Staphylococcus aureus with cells bearing IgG
      antibodies on the surface. After treating lymphocytes with goat anti-human
      IgG(H+L), the IgG-positive B-lymphocytes were efficiently separated from T
      lymphocytes. Protein A covalently coupled to epoxy activated dimethylacrylamide
      (DMAA) cryogel matrix specifically bound IgG-bearing B-lymphocytes through the Fc
      region, while non-bound T-lymphocytes passed through the column. More than 90% of
      the B-lymphocytes were retained in the column while the cells in the breakthrough
      fraction were enriched in T-lymphocytes (81%). The viability of the T-lymphocytes
      isolated was greater than 90%. The bound lymphocytes released by human or dog IgG
      recovered 60-70% of the B-cells without significantly impairing the cell
      viability. The technique can be applied in general to cell separation systems
      where IgG antibodies against specific cell surface markers are available.

PMID- 14659911
TI  - The murine myeloid cell line 32Dcl3 as a model system for studying neutrophil
      functions.
AB  - The murine myeloid cell line 32Dcl3 is one of the few cell lines that can
      terminally differentiate into neutrophils. Granulocyte colony-stimulating factor
      (G-CSF) drives the differentiation of these cells; therefore, G-CSF receptor
      signaling for neutrophil proliferation and differentiation has been studied
      extensively using this cell line as a model. Differentiated 32Dcl3 cells exhibit
      a striking morphologic similarity to normal neutrophils; however, the degree to
      which differentiated 32Dcl3 cells are functionally similar to normal neutrophils
      remains unknown. In this study, we compared the function of differentiated 32Dcl3
      cells with mouse neutrophils. Our results demonstrate that a subclone of
      differentiated 32Dcl3 cells (32Dcl3C) exhibits normal neutrophil functions of
      phagocytosis, degranulation, adhesion and shape change in response to appropriate
      stimuli. These observations suggest that this cell line can serve as an effective
      model system to study similar mature neutrophil functions. However, 32Dcl3C cells
      fail to produce superoxide in response proper stimuli.

PMID- 14659912
TI  - Development of an MHC-class I peptide selection assay combining nanoparticle
      technology and matrix-assisted laser desorption/ionisation mass spectrometry.
AB  - Human leukocyte antigen (HLA)-bound peptides are central for recognition of
      infected/transformed cells by T cells, and have formed the basis for many
      immunotherapy strategies. Epitopes from a given protein sequence (e.g. from viral
      proteins or oncoproteins) can be predicted by algorithms, as individual HLA
      receptors bind peptides through defined binding motifs. Peptides with the highest
      predicted binding score are then normally tested for their binding ability in
      binding assays. However, with the assays already established, only one peptide
      can be tested for binding per assay. This is certainly not a reflection of the in
      vivo situation, where several peptides generated via the major histocompatability
      complex (MHC)-class I processing pathway compete for HLA-receptor binding. Here,
      we describe the development of a method that can mimic the competition between
      multiple peptides for binding to a single HLA receptor molecule. We used silica
      nanoparticles with immobilised HLA-A2 complexes to screen HLA-A2 binder-peptides
      out of a known peptide mixture. The washed beads were analysed for selectively
      bound peptides by matrix-assisted laser desorption/ionisation (MALDI) mass
      spectrometry. The advantage of the system is that the bound peptides can be
      unambiguously identified without any prior modification (e.g. radioactive or
      fluorescence labelling), even from complex peptide mixtures.

PMID- 14659913
TI  - Monitoring indirect presentation of alloantigens by utilizing the autologous
      processing machinery of dendritic cells in-vitro.
AB  - BACKGROUND: Judicious individualization of immunosuppression protocols requires
      the ability to monitor the recipients' specific immune response towards the
      allograft. While several indirect presentation studies have been reported,
      currently there are no consistently reliable means to assess the state of
      transplant acceptance. A potential explanation might be the lack of established
      kinetics for in-vitro indirect presentation assays. METHODS: Dendritic cell (DCs)
      were used as self-specific "processing machinery" for the generation of
      allogeneic peptide repertoire tailored by the individual's capacity to process
      antigens via the indirect pathway. The kinetics of antigen processing and
      presentation of newly acquired antigens was then assessed to define the
      following: (1) Optimal time to introduce apoptotic-allogeneic cells to DCs; (2)
      optimal time for processing before induction of DC maturation; and (3) optimal
      time for stimulation of autologous T cells by the pulsed DCs. RESULTS: Altering
      kinetic parameters associated with time allotted for antigen processing; antigen
      presentation and DCs maturation, showed substantial variations in the level of T
      cell activation, as was documented by mixed lymphocyte reaction (MLR)-like
      proliferation assays. Further experiments using allogeneic cellular extracts
      showed similar variations in T cell stimulation by monitoring T cell precursor
      frequencies and interferon (IFN)-gamma secretion ELISPOT assays. Using the
      appropriate kinetic parameters, we have also shown difference in T-cell-subsets
      (CD4, CD8) precursor frequencies and cytokine secretion in response to different
      antigenic sources. CONCLUSIONS: The ability to construct an in-vitro, recipient
      tailored, donor-specific, indirect presentation assay is dependent on essential
      kinetic parameters associated with antigen processing and presentation, as
      described in this report. Moreover, the use of this approach may circumvent the
      need for identifying specific immunogenic peptides for cancer-related or other
      vaccine-development studies.

PMID- 14659914
TI  - Inclusion of a non-immunoglobulin binding protein in two-site ELISA for
      quantification of human serum proteins without interference by heterophilic serum
      antibodies.
AB  - Measurement of human serum molecules with two-site ELISA can be biased by the
      presence of human heterophilic anti-animal immunoglobulin antibodies (HAIA) that
      cause false-positive signals by cross-linking the monoclonal (mAb) and/or
      polyclonal antibodies (pAb) used for the pre- (capture) and post-analyte steps
      (detection). To evaluate a novel ELISA format designed to avoid interference by
      HAIA, a target-specific non-immunoglobulin (Ig) affinity protein (affibody) was
      used to replace one of the antibodies. First, a human IgA-binding affibody
      (Z(IgA)) selected by phage display technology from a combinatorial library of a
      single Staphylococcus aureus protein A domain was used. The detection range of
      IgA standard using an ELISA based on Z(IgA) for capture and goat pAb against IgA
      (pAb(IgA)) for detection was comparable with that of using pAb(IgA) for both
      capture and detection. Secondly, another affibody (Z(Apo)) was combined with mAb
      and used to detect recombinant human apolipoprotein A-1. The affibody/antibody
      ELISAs were also used to quantify human serum levels of IgA and apolipoprotein
      A1. To verify that human serum did not cause false-positive signals in the
      affibody/antibody ELISA format, the ability of human serum to cross-link
      affibodies, mAb (mouse or rat) and/or pAb (goat) displaying non-matched
      specificities was assessed; affibodies and antibodies were not cross-linked
      whereas all combinations of mAb and/or pAb were cross-linked. The combination of
      affibodies and antibodies for analysis of human serum molecules represents a
      novel two-site ELISA format which precludes false-positive signals caused by
      HAIA.

PMID- 14659915
TI  - Limitations of monoclonal antibodies for monitoring of fungal aerosols using
      Penicillium brevicompactum as a model fungus.
AB  - Molds are ubiquitous in every environment and many species have been recently
      associated with an increase in opportunistic infections in immunocompromised
      patients or the exacerbation of asthmatic episodes in allergic patients. The
      degree of environmental contamination with fungi thus needs to be monitored and
      in this study we report the development of a monoclonal antibody (mAb)-mediated
      enzyme-linked immunosorbent assay (ELISA) for the detection of spores of
      Penicillium brevicompactum in experimental model aerosols. In addition, we have
      investigated the influence of different parameters of air sampling and sample
      recovery on ELISA performance. MAbs were produced with standard hybridoma
      techniques and cross-reactivities were determined against spores of 53 fungal
      species by indirect ELISA. Standardized experimental fungal aerosols were
      collected with the Button Personal Inhalable Aerosol Sampler onto polycarbonate
      or polytetrafluoroethylene filters (PTFE) and the effects of different extraction
      buffers and filter agitation methods during sample processing on spore recovery
      and ELISA detection were investigated. Five mAbs were produced and all of them
      cross-reacted with several of 31 related Aspergillus, Penicillium and Eurotium
      species. However, cross-reactivities with 21 non-related fungi were rare. Spores
      were recovered in much higher numbers from polycarbonate filters (PFs) than from
      polytetrafluoroethylene filters. Optical densities (ODs) in ELISA were higher for
      spores collected into carbonate coating buffer (CCB) than phosphate-buffered
      saline (PBS). Filter bath sonication following filter vortexing had no positive
      effects on ELISA sensitivity. The cross-reactivity patterns of mAbs suggest that
      Aspergillus and Penicillium species share multiple antigens. Quantitative ELISA
      results for fungal aerosols were found to be influenced by differential sample
      processing and thus method standardization will be essential to maintain the
      comparability of immunometric monitoring results.

PMID- 14659916
TI  - Direct isolation of recombinant human antibodies against group B Neisseria
      meningitidis from scFv expression libraries.
AB  - The successful generation of human antibodies from large nai;ve antibody
      libraries requires iterative selection steps. Here, we describe a new and fast
      method for the isolation of high affinity antibodies directly from human single
      chain Fv antibody (scFv) expression libraries. Escherichia coli scFv expression
      libraries were made from peripheral blood lymphocytes from four individuals
      vaccinated with group B Neisseria meningitidis outer membrane vesicle (OMV)
      vaccine. Forty thousand clones were directly screened for antibodies binding N.
      meningitidis strain 44/76 (B:15:P1.7,16). Of 430 specific clones detected, 225
      candidates were isolated and re-screened against the N. meningitidis strains NZ
      98/254 (B:4:P1.7b,4) giving 4% cross-reactive clones. Antibodies were further
      characterized by DNA sequencing, ELISA and surface plasmon resonance (SPR)
      analysis, showing broad V-gene diversity and nanomolar scFv affinities.
      Antibodies derived by this method may assist in the discovery and development of
      new vaccine antigens as well as therapeutic antibody agents for the treatment of
      meningococcal diseases.

PMID- 14659917
TI  - SeroGRID: an improved method for the rapid selection of antigens with disease
      related immunogenicity.
AB  - Screening of cDNA expression libraries derived from human tumors with autologous
      sera (SEREX) permits the definition of immunogenic antigens in individual cancer
      patients. However, only a minority of SEREX-derived cDNA clones show a clear
      cancer-relatedness in the sense that circulating autoantibodies to them occur
      exclusively in the sera of tumor patients but not in healthy individuals.
      Evaluation of multiple SEREX-defined clones in serological assays using panels of
      allogeneic sera from cancer patients as well as appropriate control groups is an
      important step towards focussing on the relevant antigens. This in turn is the
      basis for defining disease parameters of diagnostic and prognostic
      significance.Here, we show that seroreactivity of multiple SEREX-derived antigens
      can be simultaneously evaluated using a rapid and versatile high throughput
      procedure, which we call SeroGRID.

PMID- 14659918
TI  - Assessment of two methods for handling blood in collection tubes with RNA
      stabilizing agent for surveillance of gene expression profiles with high density
      microarrays.
AB  - Genome-wide expression studies of human blood samples in the context of
      epidemiologic surveillance are confronted by numerous challenges-one of the
      foremost being the capability to produce reliable detection of transcript levels.
      This led us to consider the Paxgene Blood RNA System, which consists of a
      stabilizing additive in an evacuated blood collection tube (PAX tube) and a
      sample processing kit (PAX kit). The PAX tube contains a solution that inhibits
      RNA degradation and gene induction as blood is drawn into the tube. The stability
      of RNA in PAX tubes under conditions for practical clinical applications has been
      determined by RT-PCR, but has not been assessed at the transcriptome level on
      Affymetrix microarrays. Here, we report a quality assured and controlled protocol
      that is capable of producing reliable gene expression profiles using the GeneChip
      system with RNA isolated from PAX tubes. Using this protocol, we compared quality
      metrics and gene-expression profiles of RNA, extracted from blood in PAX tubes
      that sat at room temperature for 2 h, with that of blood in PAX tubes incubated
      at room temperature for 9 h followed by storage at -20 degrees C for 6 days. Of
      numerous metrics, differences between the two handling methods were detected for
      the level of DNA contamination, RNA yield, and double stranded cDNA yield.
      Analysis of variance of gene-expression revealed small but significant
      differences between the handling methods. These results contribute to the
      determination of protocols for clinical studies and progress us towards the goal
      of using the transcriptome in diagnosis and surveillance.

PMID- 14659919
TI  - Optimization of recombinant vaccinia-based ELISPOT assay.
AB  - The ELISPOT assay has been considered as one of the most sensitive assays to
      measure antigen-specific CD8 T cells in vitro. Recently, recombinant vaccinia was
      successfully used to express internally processed target antigens in host cells
      in direct ex-vivo ELISPOT assays. However, the background in these assays was
      relatively elevated, and the risk of killing effector T cells was high.
      Therefore, we examined in this study an alternative approach where the
      replication of recombinant vaccinia virus was inhibited by the usage of Cidofovir
      in vitro. Our data indicate that recombinant vaccinia-infected target cells
      treated with Cidofovir retained their functional activity and present internally
      processed antigens more efficiently to T cells than non-treated ones. We also
      identify the optimum doses of Cidofovir to be in the range of 0.75-0.075
      microg/ml. Thus, Cidofovir treatment of the target cells prior to antigen
      stimulation could be a useful methodology to increase the sensitivity of the
      ELISPOT assay.

PMID- 14659920
TI  - Accurate and statistically verified quantification of relative mRNA abundances
      using SYBR Green I and real-time RT-PCR.
AB  - Among the many methods currently available for quantifying mRNA transcript
      abundance, reverse transcription-polymerase chain reaction (RT-PCR) has proved to
      be the most sensitive. Recently, several protocols for real-time relative RT-PCR
      using the reporter dye SYBR Green I have appeared in the literature. In these
      methods, sample and control mRNA abundance is quantified relative to an internal
      reference RNA whose abundance is known not to change under the differing
      experimental conditions. We have developed new data analysis procedures for the
      two most promising of these methodologies and generated data appropriate to
      assess both the accuracy and precision of the two protocols. We demonstrate that
      while both methods produce results that are precise when 18S rRNA is used as an
      internal reference, only one of these methods produces consistently accurate
      results. We have used this latter system to show that mRNA abundances can be
      accurately measured and strongly correlate with cell surface protein and
      carbohydrate expression as assessed by flow cytometry under different conditions
      of B cell activation.

PMID- 14659921
TI  - Isolation and transplantation of allogeneic pulmonary endothelium derived from
      GFP transgenic mice.
AB  - The isolation of primary endothelial cells from murine tissues has long been a
      challenge and remains a difficult task. Using GFP transgenic C57/BL6 mice as
      donors, we describe a reliable method to isolate pulmonary endothelial cells by
      flow cytometry after staining with DiI-Ac-low density lipoprotein (LDL). After
      mechanical dissociation of murine lung tissue and enzymatic digestion, adherent
      cells can be quickly stained and sorted by flow cytometry. The isolated cells
      express endothelial cell markers such as CD31, MECA32 and CD106 and stained
      positive for Isolectin B4. After 50-fold expansion using standard endothelial
      growth media, cells could be transplanted into lethally irradiated allogeneic
      hosts and were detectable using fluorescence microscopy up to 24-h post
      transplantation in pulmonary tissue.

PMID- 14659922
TI  - The detection of anti-erythropoietin antibodies in human serum and plasma. Part
      I. Validation of the protocol for a radioimmunoprecipitation assay.
AB  - Rare cases of unexplained sudden severe anemia or red cell aplasia and resistance
      to recombinant human erythropoietin (rHuEPO) in patients with chronic renal
      failure (CRF) have been attributed to the development of anti-EPO antibodies. The
      development and validation of a radioimmunoprecipitation (RIP) assay to detect
      human anti-EPO antibodies in serum or plasma has been hampered by the lack of
      purified antibody to fully characterize and validate the assay. We have prepared
      an affinity-purified human antibody to EPO and used the antibody to characterize
      and validate a sensitive and reproducible RIP assay that can qualitatively
      measure anti-EPO antibody in serum or plasma samples. The lower limit of
      detection of the assay is 8 ng/ml of purified antibody. The threshold for
      detecting antibody is > or =0.9% cpm bound. The precision of the assay using
      purified antibody standards ranges from 5.8% to 15.3% and the precision of the
      assay using dilutions of the positive control ranges from 15.9% to 18.7%. EPO in
      the samples did not interfere with detection of the anti-EPO antibody except at
      high concentrations.

PMID- 14659923
TI  - Cervical spine curvature during simulated whiplash.
AB  - OBJECTIVE: To develop a new method to describe cervical spine curvature and
      evaluate the potential for injury in the upper and lower cervical spine during
      simulated whiplash. DESIGN: A method was developed to integrate the upper and
      lower cervical spine rotations and describe the spine curvature. BACKGROUND: In
      vivo and in vitro whiplash simulations have documented the development of an S
      shape curvature with simultaneous upper cervical spine flexion and lower cervical
      spine extension immediately following rear-impact. Investigators have
      hypothesized that the injury potential is highest during the S-shape phase.
      However, little data exist on the spine curvature during whiplash and its
      relation to spine injury. METHODS: A biofidelic model and a bench-top whiplash
      apparatus were used in an incremental rear-impact protocol (maximum 8 g) to
      simulate whiplash of increasing severity. To describe the spine curvature, the
      upper and lower cervical spine rotations were normalized to corresponding
      physiological limits. RESULTS: Average peak lower cervical spine extension first
      exceeded the physiological limits (P<0.05) at a horizontal T1 acceleration of 5
      g. Average peak upper cervical spine extension exceeded the physiological limit
      at 8 g, while peak upper cervical spine flexion never exceeded the physiological
      limit. In the S-shape phase, lower cervical spine extension reached 84% of peak
      extension during whiplash. CONCLUSIONS: Both the upper and lower cervical spine
      are at risk for extension injury during rear-impact. Flexion injury is unlikely.

PMID- 14659924
TI  - Anterior glenohumeral force/translation behavior with and without rotator cuff
      contraction during clinical stability testing.
AB  - OBJECTIVE: Measure stiffness of the glenohumeral joint during clinical laxity
      testing with and without muscular contraction of the Internal rotators. DESIGN:
      Cross-sectional study of normal shoulders. BACKGROUND: Clinical examination for
      shoulder instability is based on subjective impression, and is only performed
      passively. Our study presents a method for quantitative clinical examination of
      the shoulder under both passive and active muscle contraction conditions. We
      hypothesized that in a normal shoulder, contraction of the internal rotators will
      increase the stiffness of the glenohumeral joint, effectively constraining the
      head of the humerus against anterior directed forces. METHODS: Ten subjects were
      instrumented with electromagnetic sensors to record glenohumeral linear
      displacements. A mini-force transducer recorded forces applied to subjects during
      anterior drawer testing (forced anterior glenohumeral displacement), which was
      performed passively, and during isometric contraction of internal rotators.
      RESULTS: Only mild contraction of the internal rotators is needed to
      significantly increase the stiffness to anterior directed forces. Greater
      muscular activation does not result in further increased stiffness. CONCLUSION:
      Objective measurement of glenohumeral stiffness during passive and active
      muscular contraction may be useful for evaluating the capacity of rotator cuff
      muscles to stabilize the shoulder. The concept of more strength is better, for
      rotator cuff strengthen programs is questioned.

PMID- 14659925
TI  - Benefits of an anatomical reconstruction of the humeral head during shoulder
      arthroplasty: a finite element analysis.
AB  - OBJECTIVE: To study the influence of the shape of the prosthetic humeral head on
      shoulder biomechanics and then to evaluate the benefits of an anatomical
      reconstruction of the humeral head after shoulder arthroplasty. DESIGN: A 3D
      numerical model of a healthy shoulder was reconstructed. The model included the
      proximal humerus, the scapula and, for stability purposes, the subscapularis,
      infraspinatus and supraspinatus rotator cuff muscles. BACKGROUND: Shoulder
      prostheses used nowadays, called third generation, allow for a better adaptation
      of the implant to the anatomy of the proximal humerus than previously used
      implants. However, no biomechanical study has shown the benefits of this
      anatomical reconstruction of the humeral head. METHODS: The model was used to
      compare the biomechanics of a shoulder without implant with the biomechanics of
      the same shoulder after humeral hemiarthroplasty. Two humeral components were
      tested: a second-generation prosthesis and an implant with an anatomically
      reconstructed humeral head. RESULTS: The anatomical reconstruction of the humeral
      head restored the physiological motions and limited eccentric loading of the
      glenoid. Conversely, the second-generation implant produced contact forces in the
      superior extremity of the glenoid surface leading to bone stresses up to 8 times
      higher than for the intact shoulder. CONCLUSIONS: This analysis provided insights
      into the mechanical effects of different reconstructions of the humeral head and
      highlighted the advantages of anatomical reconstructions of the humeral head
      during shoulder arthroplasty.

PMID- 14659926
TI  - Muscle fatigue of the elbow flexor muscles during two intermittent exercise
      protocols with equal mean muscle loading.
AB  - OBJECTIVE: Whether different muscle-loading patterns with the same mean load have
      a similar influence on the resultant muscle fatigue is still unknown. This study
      investigated the influence of two intermittent exercise protocols, with equal
      mean muscle loading, on the mechanical and myoelectrical signs of fatigue in the
      elbow flexor muscles. DESIGN: Ten subjects performed two 20-min long intermittent
      isometric elbow flexion tasks. The exercise period load for the low force
      intermittent test was 25% of the maximum voluntary contraction, with a work-cycle
      time of 20 s and a duty cycle of 0.5. The high force intermittent exercise
      protocol had an exercise period load of 50% maximum voluntary contraction, a
      cycle time of 20 s and a duty cycle of 0.25. METHODS: Muscle fatigue was
      quantified both by measuring the maximal voluntary contraction torque before and
      after the intermittent exercises, and also by the temporal changes observed in
      the electromyography signal. RESULTS: Both muscle-loading patterns induced a 15%
      decrease in maximum voluntary contraction. However, the electromyographic
      spectral changes during the intermittent static contractions varied between the
      two protocols. CONCLUSIONS: Variation in muscle load without loss in productivity
      can affect the physiological responses. The results also showed that different
      methods to assess muscle fatigue sometimes provide different information on the
      resultant fatigue.

PMID- 14659927
TI  - Kinematics of the ulna during pronation and supination in a cadaver study:
      implications for elbow arthroplasty.
AB  - OBJECTIVE: Aim of this study was to exactly describe and quantify kinematics of
      the ulna during pro- and supination. DESIGN: Biomechanical study in fresh frozen
      cadavers. BACKGROUND: A previous MRI study revealed a varus/valgus motion of the
      ulna averaging 7.1 degrees during pro-/supination. Axial rotation, however, could
      not be quantified. METHODS: Sixteen arms were examined in a new apparatus that
      fixed the humerus on a template and allowed forearm rotation. Motion of a
      Kirschner wire placed in the ulna was recorded in steps of 30 degrees by two
      perpendicularly arranged charge coupled device cameras during pro- and
      supination. RESULTS: From supination to pronation the ulna showed a semi-lunar
      evasive motion in the coronal and transverse plane with an initial varus shift,
      then a dorsal and finally a valgus shift. Motion in the coronal plane averaged
      14.14 degrees (SD 4.78). Valgus angles of the ulna in 30 degrees, 60 degrees and
      90 degrees pronation were significant (P<0.05) to each other and the neutral
      position. Varus angles of the ulna in 30 degrees, 60 degrees and 90 degrees
      supination (P<0.01) were significant to each other and the neutral position.A
      maximum ulnar axial pronation rotation of 3.2 degrees (SD 2 degrees ) was noted.
      Axial rotation angles of 90 degrees and 60 degrees of pronation were significant
      to each other and to the neutral position (P<0.05), respectively. CONCLUSIONS: To
      prevent increased stress on the bone-cement interface in elbow arthroplasty, a
      mean axial rotation of at least 3.2 degrees should be possible.

PMID- 14659928
TI  - Sex comparison of extensibility, passive, and active stiffness of the knee
      flexors.
AB  - OBJECTIVE: To compare extensibility, and passive and active stiffness of the knee
      flexors between males and females. DESIGN: An experimental design utilized 15
      males and 15 females to identify sex differences in active extensibility, and
      active and passive stiffness of the knee flexors. BACKGROUND: Muscle stiffness
      appears to contribute to joint stability from both mechanical and neuromuscular
      perspectives. Differences in knee flexor stiffness may partially explain higher
      female anterior cruciate ligament injury rates. METHODS: Active knee flexor
      extensibility was assessed as subjects extend the knee from a fixed hip position,
      measuring the final knee position. Passive knee flexor stiffness was calculated
      as the slope of the moment-angle curve resulting from controlled passive knee
      extension. Active knee flexor stiffness was assessed by loading the lower
      extremity with 10% total body mass, and measuring the damping effect of the knee
      flexors on imposed vibratory motion about the knee joint. RESULTS: Females
      displayed greater active extensibility (P<0.05), while males displayed greater
      active (P<0.05) and passive (P<0.05) knee flexor stiffness. Sex differences in
      active and passive knee flexor stiffness were not significant following
      normalization to anthropometric characteristics. CONCLUSIONS: The knee flexor
      musculature in males is less extensible and displays greater active and passive
      stiffness compared to females. However, these differences may be functions of
      greater mass and height in males.

PMID- 14659929
TI  - Alterations in lower extremity movement and muscle activation patterns in
      individuals with knee osteoarthritis.
AB  - OBJECTIVE: The purpose of this study was to investigate lower extremity movement
      and muscle activation patterns in individuals with knee osteoarthritis and
      healthy age- and gender-matched control subjects. DESIGN: This study utilized a
      non-randomized case-control design to compare 24 subjects with unilateral
      symptomatic knee osteoarthritis to 24 age- and gender-matched control subjects
      without knee osteoarthritis. BACKGROUND: It is hypothesized that knee
      osteoarthritis is associated with altered lower extremity movement and muscle
      activation patterns. METHODS: A gait analysis was performed to determine the
      lower extremity movement and muscle activation patterns when walking on a level
      surface at 1.12 to 1.34 m/s and while descending a 20 cm step. Paired t-tests
      were used to compare the average of five trials between the groups. RESULTS:
      Subjects with knee osteoarthritis demonstrated less excursion of the knee in the
      sagittal plane from heelstrike to peak flexion before midstance (i.e. during
      loading). Subjects with knee osteoarthritis also demonstrated reduced peak
      vertical ground reaction forces relative to body weight. The muscle activity
      patterns were also different between the groups. The vastus lateralis, medial
      hamstrings, tibialis anterior and medial gastrocnemius were on approximately 1.5
      times longer than the same muscles in the control subjects. Additionally,
      significant increases in muscle co-activation were also observed in individuals
      with knee osteoarthritis during walking. Similar findings were observed when the
      subject descended a 20 cm step.

PMID- 14659930
TI  - Determination of lower extremity anthropometric parameters using dual energy X
      ray absorptiometry: the influence on net joint moments during gait.
AB  - OBJECTIVE: The purpose of this study was threefold: (1) to report on a method of
      determining lower extremity anthropometric data using dual energy X-ray
      absorptiometry, (2) to compare values obtained with this method to predictions
      from cadaver-based estimates, and (3) to quantify the extent to which these data
      affect the calculation of net joint moments during walking. BACKGROUND:
      Anthropometric data used in inverse dynamics equations are often estimated from
      older cadaveric specimens. A practical method for determining population-specific
      data is needed. METHODS: Using DXA scans obtained from 20 healthy adults, the
      mass, center of mass, and moment of inertia of each lower extremity segment were
      determined and compared to cadaver-based estimates. In addition, gait analysis
      was performed on 10 of these subjects, and net joint moments (sagittal plane)
      were calculated at the ankle, knee, and hip using anthropometric data obtained
      from (a) DXA, and (b) cadaver-based estimates. RESULTS: Statistically significant
      differences were identified for DXA-derived and cadaver-based anthropometric
      values. Overall, moment curves computed using the two data sets differed more
      during the swing phase than during the stance of gait. CONCLUSIONS: DXA appears
      to be an appropriate method for obtaining population-specific anthropometric
      data. Moment calculations for activities involving high accelerations and no
      ground reaction forces (i.e. swing phase of gait, kicking, etc.) would be most
      influenced by the differences between the anthropometric data sets.

PMID- 14659931
TI  - Posture of the trunk in the sagittal plane is associated with gait in community
      dwelling elderly population.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether abnormal posture of
      the trunk in the sagittal plane would affect gait and functional performance in
      the elderly. BACKGROUND: There have been very few reports on whether posture of
      the trunk is related to gait and functional performance. METHODS: The study group
      included 237 participants with a mean age of 80.0 years (range 65-94 years). The
      posture of the trunk in a standing position of the sagittal plane was classified
      into five groups. We investigated the relationship between the trunk posture in
      the sagittal plane and age with gait parameters and functional performance such
      as timed up & go test and functional reach. RESULTS: In the elderly subjects of
      normal posture, there was no difference between those in the 65-79 years age
      group and those in the 80 years and older age group in terms of any gait
      parameters. Walking abilities were significantly decreased in the abnormal
      posture groups. Among the abnormal posture groups, elderly in the lumbar kyphosis
      group had walking disabilities that did not differ between age groups, whereas
      gait disturbance in the thoracic kyphosis group showed a positive relation with
      age. CONCLUSIONS: Posture of the trunk in the sagittal plane was associated not
      only with the distance and time parameter of gait, but also with functional
      performance in the elderly.

PMID- 14659932
TI  - Orthotic intervention in forefoot and rearfoot strike running patterns.
AB  - OBJECTIVE: To compare the differential effect of custom orthoses on the lower
      extremity mechanics of a forefoot and rearfoot strike pattern. DESIGN: Fifteen
      subjects ran with both a forefoot and a rearfoot strike pattern with and without
      orthoses. Lower extremity kinematic and kinetic variables were compared between
      strike pattern and orthotic conditions. BACKGROUND: Foot orthoses have been shown
      to be effective in controlling excessive rearfoot motion in rearfoot strikers.
      The effect of orthotic intervention on rearfoot motion in forefoot strikers has
      not been previously reported. METHODS: Five trials were collected for each
      condition. Peak rearfoot eversion, eversion excursion, eversion velocity, peak
      inversion moment, and inversion work were compared between conditions. Kinematic
      variables in the sagittal plane of the rearfoot and in the frontal and sagittal
      plane of the knee were also determined. RESULTS: Increased rearfoot excursions
      and velocities and decreased peak eversion were noted in the forefoot strike
      pattern compared to the rearfoot strike pattern. Orthotic intervention,
      however,did not significantly change rearfoot motion in either strike pattern.
      Reductions in internal rotation and abduction of the knee were noted with
      orthotic intervention. CONCLUSIONS: Foot orthoses do not differentially effect
      rearfoot motion of a rearfoot strike and a forefoot strike running pattern.
      Orthotic intervention has a larger and more systematic effect on rearfoot
      kinetics compared to rearfoot kinematics.

PMID- 14659933
TI  - The role of selected extrinsic foot muscles during running.
AB  - OBJECTIVE: To determine the kinematic, kinetic and EMG responses to perturbations
      of the foot by running in varus, neutral, and valgus-wedged shoes. DESIGN: Within
      subjects study comparing kinematics, kinetics and EMG while running in three
      different shoe conditions. BACKGROUND: Excessive pronation has been cited as a
      key contributor to many types of running injuries. However, the roles of the
      extrinsic foot muscles (those that control motion of the foot) during the stance
      phase of running have not been adequately identified, which is critical to
      determining the relationship between pronation and injury. METHODS: Ten males ran
      in varus, valgus, and neutral-wedged shoes while three-dimensional kinematic and
      kinetic data and EMG data were collected. Surface EMG data were collected from
      the tibialis anterior, peroneus longus, medial and lateral gastrocnemius, and
      soleus. Indwelling EMG was obtained from the tibialis posterior. The net joint
      moment, power, and total positive and negative work was calculated in the frontal
      plane. EMG onset, offset, and integrated values were reported. RESULTS: The
      maximum eversion angle, maximum inversion moment and total negative work done in
      the frontal plane were greatest while running in the valgus shoe and least in the
      varus shoe. The greater joint moment was not accompanied by changes in muscle
      activation patterns, although the tibialis posterior data were inconclusive in
      this respect. CONCLUSIONS: Greater pronation leads to greater energy absorption
      in the foot invertor muscles and tendons. While not conclusive, the EMG data
      suggest that for these muscles there was not a neuromuscular adaptation to the
      perturbation.

PMID- 14659934
TI  - The influence of walking speed and footwear on plantar pressures in older adults.
AB  - OBJECTIVE: To identify the influence of walking velocity and footwear condition
      on plantar pressure variables in healthy older adults. DESIGN: Single session
      data collection during varying speed and footwear conditions. BACKGROUND:
      Elevated plantar pressures are concerning due to the risk of tissue injury,
      ulceration, and pain. In young adults, increases in plantar pressure have been
      documented with faster walking speeds and when walking barefoot compared to
      wearing shoes. These relationships have not been systematically explored in older
      adults. METHODS: Key plantar pressure factors were recorded as subjects walked
      barefoot and in comfortable walking shoes across a 10 m walkway at three
      predetermined velocities (57, 80, 97 m/min). Separate 3x2 analyses of variance
      with repeated measures identified significant differences in pressure, force, and
      contact area in eight anatomically defined foot regions across walking speeds and
      between footwear conditions. RESULTS: Faster walking resulted in higher pressures
      under all foot regions except for the arch and lateral metatarsal (P</=0.001),
      due primarily to greater forces under the heel, medial metatarsal and toes
      (P</=0.001). Compared to wearing shoes, barefoot heel pressure was elevated
      (P</=0.001) due to reduced heel contact area (P<0.001); pressure under the
      central metatarsals was higher (P</=0.001) owing to greater central metatarsals
      force (P<0.001). CONCLUSIONS: Two conditions were associated with higher plantar
      pressures in the older adults studied: faster speeds and barefoot walking.

PMID- 14659935
TI  - A non-invasive technique for assessing innominate bone motion.
AB  - OBJECTIVE: To determine the suitability of a magnetic tracking device to measure
      pelvic bone range of motion based on palpated and digitized pelvic landmarks.
      DESIGN: A repeated measures study was conducted in two experiments to determine
      the reliability and validity of innominate bone range of motion measured with a
      magnetic tracking device in healthy subjects through passive hip abduction and
      external rotation. BACKGROUND: Because of the anatomical position of the pelvic
      joints, kinematic analysis of joint motion is difficult. Accurate and precise
      measurements typically require highly invasive techniques involving implantation
      of titanium markers and exposing the subject to multiple radiographs. There is a
      need for a practical and accurate measurement method that will allow researchers
      and clinicians to accurately and reliably evaluate motion in the pelvis. METHODS:
      Innominate bone angles were measured for two static hip postures from the 3D
      spatial coordinates of the pelvic landmarks. By palpating and subsequently
      digitizing pelvic landmarks using an electro-magnetic tracking device the 3D
      coordinates were obtained. Palpated results were validated using CT scans and a
      metallic bead attached to the palpated landmarks. RESULTS: The mean range of
      innominate bone motion was between 3 degrees and 4 degrees (transverse plane) for
      each side with large variability across the subjects in the range of motion.
      Despite this variability, the measurements were found to be reliable and valid.

PMID- 14659936
TI  - Correlations between the step activity monitor and the DynaPort ADL-monitor.
AB  - OBJECTIVE: This study was performed to evaluate correlations between the DynaPort
      activity of daily living monitor and the step activity monitor. DESIGN:
      Experimental study with repeated measures. BACKGROUND: Physical activity becomes
      more important to assess quality of life, e.g. after clinical interventions such
      as joint replacement surgery. METHODS: Nine subjects wore both devices
      simultaneously for two days. Limitations and technical problems caused by the
      devices were assessed by a questionnaire. Correlation coefficients were
      calculated between parameters derived from both instruments. RESULTS: Only small
      limitations and problems were reported. Significant correlations were found
      between the number of steps (step activity monitor) and the percentage of
      locomotion (DynaPort) (r=0.95), between the number of steps and the physical
      activity index (DynaPort) (r=0.71) and between the physical activity index and
      the percentage of locomotion (r=0.76). Wilcoxon-tests between the first and
      second measurement of each subject did not reveal significant differences but
      correlation coefficients were poor (r=0.16-0.36). CONCLUSIONS: After one day of
      simultaneously wearing both devices, the percentage of locomotion can be obtained
      using only the step activity monitor for additional days. Poor correlations
      between the first and the second measurements of each subject underline the
      necessity to record further days to acquire the level of human physical activity.

PMID- 14659937
TI  - Influences of variation in force application on tibial displacement and strain in
      the anterior cruciate ligament during the Lachman test.
AB  - OBJECTIVE: The purpose of this study was to examine the influence of Lachman test
      performance technique on tibial displacement and strain in the anterior cruciate
      ligament. DESIGN: Model simulation of experimental Lachman test performance by
      trained clinicians. BACKGROUND: Differences in clinician hand placement during
      Lachman test performance have been observed. METHODS: A two-dimensional computer
      sagittal plane model of the knee was designed to simulate experimentally observed
      Lachman test performance, and determine anterior cruciate ligament strain and
      tibial translation that occurred during variation in clinician hand placement and
      force magnitude. RESULTS: Anterior cruciate ligament strain and tibial
      translation were greater under conditions mimicking clinician hand placement
      utilizing a more proximal force application on the tibia. CONCLUSIONS: Tibial
      translation and strain behavior of the anterior cruciate ligament during the
      Lachman test appear to be influenced by clinician hand position used in the
      application of force to the tibia.

PMID- 14659938
TI  - Metabolism, tissue disposition, and excretion of 1,2-bis(2,4,6
      tribromophenoxy)ethane (BTBPE) in male Sprague-Dawley rats.
AB  - A single oral dose of [14C] 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) was
      administered to conventional and bile-duct cannulated male Sprague-Dawley rats.
      Tissue disposition, excretion and metabolism was determined. BTBPE is a low
      volume brominated flame retardant used in resins or plastics, and toxicity data
      in peer-reviewed journals is extremely limited. BTBPE was fairly insoluble in
      lipophilic solutions, which made dose preparation difficult. The great majority
      of 14C (>94%) was excreted in the feces of both groups of rats at 72 h, and
      tissue retention was minimal. Lipophilic tissues contained the highest
      concentrations of BTBPE, e.g. thymus, adipose tissue, adrenals, lung, and skin.
      Metabolites were excreted in the urine, bile and feces, but at a very low level.
      Fecal metabolites were characterized as monohydroxylated, monohydroxylated with
      debromination, dihydroxylated/debrominated on a single aromatic ring,
      monohydroxylated on each aromatic ring with accompanying debromination, and
      cleavage on either side of the ether linkage to yield tribromophenol and
      tribromophenoxyethanol. Despite a limited quantity of stable metabolites
      extractable in the feces, non-extractable 14C levels were relatively high (39% of
      the 0-24 h fecal 14C), which suggested that BTBPE could be metabolically
      activated in the rat and covalently bound to fecal proteins and/or lipids. It was
      concluded that limited absorption and metabolism of BTBPE would occur by
      ingestion in mammals.

PMID- 14659939
TI  - Patterns of PCDDs and PCDFs in human milk and food and their characterization by
      artificial neural networks.
AB  - Artificial neural network (ANN) has been recently introduced as a tool for data
      analysis. In this study, Kohonen's self-organizing maps (SOMs), a special type of
      neural network, were applied to a set of PCDD/PCDF concentrations found in 54
      human milk and 83 food samples, which were collected in a number of countries all
      over the world. Data were obtained from the scientific literature. The purpose of
      the study was to find a potential relationship between PCDD/PCDF congener
      profiles in human milk and the dietary habits of the different countries in which
      samples were collected. The comparison of the SOM component planes for human milk
      and foodstuffs indicates that those countries with a greater fish consumption
      show also higher PCDD/PCDF concentrations in human milk. SOMs enable both the
      visualization of sample units and the visualization of congener distribution.

PMID- 14659940
TI  - Congener-specific intake fractions for PCDDs/DFs and Co-PCBs: modeling and
      validation.
AB  - Intake fractions (iFs) for emissions to air, water, and soil for 17 PCDDs/DFs and
      12 Co-PCBs were calculated with a level III multimedia model and a food-chain
      exposure model in succession. The two integrated models were tested by comparing
      the predicted and measured concentrations in the environment and by comparing
      intakes through food. Measurement-based iFs were also calculated and compared
      with the model-based iFs. The air concentrations predicted by the fate model were
      close to the median of the observed concentrations, whereas the predicted soil
      and water concentrations were one-third to one-tenth the observed concentrations.
      This difference was large in case of PCDDs and Co-PCBs, which was explained by
      the past pollution such as commercial PCB products and PCDD impurities in
      chloronitrofen (CNP) and pentachlorophenol (PCP). For fish, the predicted and
      observed exposures agreed well each other. For meat and milk, the predicted
      exposures were about 10 times the observed exposures for PCDDs/DFs, whereas the
      predicted and observed values agreed well for Co-PCBs. When the model was
      modified to consider feeding of fish meal to livestock and geographic bias in
      feed-grass production, the predicted congener profile was comparable to the
      measured profile. The comparison also suggested that chickens should be modeled
      separately from other terrestrial livestock. The model-based iFs for air emission
      of OCDD and 2378-TCDD were 0.001% and 0.1%, respectively. The iFs of most Co-PCBs
      were higher than those of PCDDs/DFs. These iF differences suggest the importance
      of the fate factor in assessing emissions of the 29 congeners.

PMID- 14659941
TI  - Organochlorine contamination in some marketable fish in Egypt.
AB  - Ten organochlorine compounds were analyzed in four species of fish (Bouri Mugil
      spp., Denis Sparus auratus, Moza Boops boops and Mousa Pegusa lascaris), from
      four Egyptian governorates (South Sinai, Suez, Port-Said and Demietta). Although
      all fish studied are bottom or near-bottom feeders, remarkable variations between
      studied species were noticed. The grand total values recorded at the studied
      governorates were in descending order: Bouri>Denis>Moza>Mousa. The highest
      concentration of pesticides was recorded in Demietta governorate fish (20-211
      ng/g of wet weight) and the p,p'-DDE dominated over the other p,p'-isomers in all
      studied fish, while dieldrin was the dominated in the studied cyclodiene
      compounds. However, hexachlorobenzene (HCB) occurred at all studied governorate
      fish except Mousa fish from South Sinai. Toxaphene was detected only in fish
      (Bouri, Denis, and Mousa) from Demietta governorate. Chlordane was not detected
      in any studied fish. The level of organochlorine pesticides contamination in fish
      from the studied governorates is relatively low and should not pose a health risk
      to consumers.

PMID- 14659942
TI  - Polychlorinated biphenyls and chlorinated pesticides in mussels from the Egyptian
      Red Sea coast.
AB  - The residues of 17 organochlorine pollutants were analyzed in bivalve
      Brachiodontes sp. collected from 11 different locations in April 2000 along the
      Egyptian Red Sea coast. The pollutants studied were 10 individual polychlorinated
      biphenyl (PCB) congeners, alpha,alpha,alpha-hexachlorocyclohexane (HCHs),
      cyclodienes (heptachlor, heptachlorepoxide, aldrin, dieldrin) and
      dichlorodiphenyltrichloroethanes (DDTs) (p,p'-DDE, p,p'-DDD and p,p'-DDT). The
      concentration of total DDTs ranged between 125 and 772 ng/g of wet weight whereas
      the concentration of the PCBs, HCHs and cyclodienes ranged from 6.7 to 66.4 ng/g;
      16.2 to 183.4 ng/g and 8.8 to 221.6 ng/g of wet weight, respectively. The levels
      are low to moderate in relation to the published data from other coastal areas.
      The present results indicate low to moderate PCBs and pesticides contamination in
      the investigated mussels except DDTs.

PMID- 14659943
TI  - The emission inventory of PCDD/PCDF in Taiwan.
AB  - Establishment of a country or region-based dioxin inventory was considered a
      crucial step toward elimination of worldwide dioxins/POPs contaminations,
      although no harmonized method for the preparation of an inventory is available at
      present. In this study, we used limited data and information to generate an
      inventory of dioxin emissions from some major sources in Taiwan. A total of 67.25
      g I-TEQ of dioxins released annually was estimated. Unlike most of the
      industrialized countries, municipal waste incineration is not the highest
      contributor for dioxins released into the atmosphere. In contrast, secondary
      copper smelting accounts for more than 39% of the total dioxin emissions, and is
      higher than those from all waste incinerators combined (23.7%). Cement kilns and
      electric arc furnaces for steels also produced significant portion (both >10%) of
      dioxins into the environment, followed by secondary aluminum smelting (6.53%),
      industrial oil combustion (5.02%) and power plants fueled by coal (5.01%). Other
      known sources are either insignificant with respect to their dioxin emissions or
      not included in this inventory due to lack of information or uncertainty of the
      results. Data presented in this report provide a general picture of dioxin
      emissions in Taiwan, but were mostly based on less reliable or representative
      information, especially with respect to emission factors from different emission
      sources. It is necessary to establish background information relative to our own
      environment at present. Upon available, the inventory should be updated
      accordingly for proper environmental management on dioxins.

PMID- 14659944
TI  - Serum PCDD/F concentration distribution in residents living in the vicinity of an
      incinerator and its association with predicted ambient dioxin exposure.
AB  - The aim of this study was to evaluate the serum polychlorinated dibenzo-p-dioxin
      (PCDD) and dibenzofuran (PCDF) concentration distribution in residents living in
      the vicinity of an incinerator and its association with annual ambient dioxin
      exposure predicted by an atmospheric dispersion model. A municipal waste
      incinerator in Northern Taiwan was chosen for this study. This incinerator had
      been in operation for 6 years at the time of this study. Using the incinerator
      site as the center, based on the simulated ambient annual average PCDD/F
      concentrations. Ninety-five volunteers, all live within a radius of 5 km from the
      incinerator for at least 5 years, who had no occupational exposure potential,
      were selected based on the population distribution in each district. The average
      serum PCDD/F concentration for these subjects living within four zones was about
      14 pg I-TEQ/g lipid. The serum distribution levels of people of the four study
      zones, however, were not consistent with the predicted ambient levels. Results
      also suggest that ambient exposure might not be the most important contributor to
      serum concentrations when compared to other exposure sources, such as dietary
      intake.

PMID- 14659945
TI  - Persistent organochlorines in the serum of the non-occupationally exposed New
      Zealand population.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and organochlorine
      pesticides were measured in the serum of a sample of the New Zealand population
      aged 15 years and older. This was the first study to obtain representative
      measures of PCDDs, PCDFs and PCBs in the adult population of an entire country.
      Serum samples were obtained in 1996-1997. Potentially occupationally exposed
      individuals were excluded. Serum samples were pooled according to stratification
      criteria for area of residence, ethnicity, age, and sex. Of the 80 possible
      strata, sufficient serum for chemical analysis was available for 60, to which
      1,834 individual samples contributed. For the PCDDs and PCDFs, most 2,3,7,8
      chlorinated congeners were measured in all strata, with a mean toxic equivalents
      concentration across all strata of 12.8 ng TEQ kg(-1) lipid. Seven PCB congeners
      were frequently measured, including the coplanar congeners #126 and #169,
      quantified in all strata. Of the pesticides and their metabolites, only beta-HCH,
      dieldrin and pp'-DDE were consistently detected across strata. There was a
      general trend of increasing concentration with age. There were no consistent
      differences between the sexes, or between people of Maori (the indigenous people
      of New Zealand) and non-Maori ethnicity. Concentrations of PCDDs and PCDFs tended
      to increase in a North-South direction, possibly reflecting greater levels of
      industrialization and population concentration, and concentrations of the
      pesticide products were highest in the South, possibly reflecting historical use
      patterns. Results were consistent with a recent study of concentrations of these
      compounds in the milk of first-time mothers.

PMID- 14659946
TI  - Polychlorobiphenyls and other organochlorine compounds in human follicular fluid.
AB  - Based on observations in animals, there is an increasing evidence that a number
      of persistent organochlorine pollutants can alter the endocrine homeostasis, this
      resulting in toxic effects in particular in the developing organism. However, the
      role of these chemicals in determining endocrine-related diseases in humans, and
      possibly a decrease of fertility, is still controversial. Exposure data
      concerning the human reproductive system are essential for risk assessment. Based
      on this, the occurrence in follicular fluid of polychlorobiphenyls (PCBs),
      2,3,7,8-chlorosubstituted polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDT)
      and its metabolites, and hexachlorobenzene (HCB) was investigated. With respect
      to PCBs, the sum of the three most abundant congeners (PCBs 138, 153 and 180) was
      1230 ng/g, lipid basis (0.37 ng/g, wet weight). Congener distribution profile
      overlapped what is usually observed in other human tissues, as blood and milk.
      PCDDs, PCDFs, p,p'-DDT and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDD)
      were below their determination limits. 1,1-dichloro-2,2-bis(4-chlorophenyl)
      ethene (p,p'-DDE) and HCB were detected in concentrations respectively in the
      order of 700 and 70 ng/g, lipid basis (approximately 0.2 and approximately 0.02
      ng/g, wet weight).

PMID- 14659947
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans from food salt samples
      processed by heat treatment in Korea.
AB  - Eight samples of processed food salt collected from five plants in Korea were
      analyzed for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) using liquid-liquid extraction, clean-up
      procedures, and high resolution gas chromatography-high resolution mass
      spectrometry. The study included the analyses of two kinds of salt product
      sample: bamboo-salt and parched salt. The levels of toxic PCDD/Fs found in the
      salt product samples were extremely low: the results revealed TEQ levels ranging
      between the sub pg TEQ/g and sub fg TEQ/g. The differences in the TEQ values of
      toxic PCDD/F were observed between the salt product samples, which were treated
      with different frequency of baking using four different fuels (firewood, pine
      wood, pine resin, and indirect heating by gas) at temperatures from 300 to 2000
      degrees C. In bamboo-salt samples, the concentrations and TEQ values of toxic
      PCDD/Fs ranged between 0.57-66 pg/g and 5.7x10(-5)-0.64 pg TEQ/g, respectively.
      PCDD/Fs levels in bamboo-salts baked by firewood were found to be higher than
      those baked by pinewood or pine resin. In parched salt samples, the
      concentrations and TEQ values of toxic PCDD/Fs ranged between 0.97-3.7 pg/g and
      0.0097-0.017 pg TEQ/g, respectively. The data was discussed regarding the
      concentration and the distribution pattern of congeners.

PMID- 14659948
TI  - Infant exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls
      (PCDD/Fs, PCBs)--correlation between prenatal and postnatal exposure.
AB  - Polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and polychlorinated
      biphenyls (PCBs) are recognized environmental endocrine disruptors, which are
      environmentally persistent and may bio-accumulate in human bodies. Pregnant and
      nursing women may pass these pollutants to their babies both trans-placentally
      and lactationally. We measured and examined correlations of the levels of PCDD/Fs
      and PCBs in perinatal venous serum, placenta, umbilical-cord serum (representing
      prenatal exposure), and breast milk (postnatal exposure). Subjects included
      pregnant women without clinical complication between the ages of 25 and 35, who
      delivered their babies during 2000.12.01 and 2001.11.30 in central Taiwan. A
      total of 20 participants were randomly selected from those provided the four
      biological specimens for analysis of 17 PCDD/Fs, and 12 dioxin-like PCBs and six
      indicator PCBs using high-resolution gas chromatography/high-resolution mass
      spectrometry. Higher PCDD/F levels were found in placenta (10.3 TEq-pg/g lipid)
      and venous serum (9.1 TEq-pg/g lipid) compared to those in breast milk (7.6 TEq
      pg/g lipid). Pearson and Spearman correlation analyses showed well association of
      PCDD/F and PCB levels between different specimens. The total dioxin/PCB level in
      milk, venous and cord serum can be well predicted by that in placenta through
      regression functions. This first study of multi-specimen correlation further
      established rather consistent ratios of these chemical concentrations in various
      specimens relative to those in venous serum.

PMID- 14659949
TI  - Real-time-monitored decrease of trichlorophenol as a dioxin surrogate in flue gas
      using iron oxide catalyst.
AB  - The decrease of trichlorophenol by injecting oxidation catalyst into a municipal
      solid waste incinerator was monitored in real time. Direct sampling atmospheric
      pressure chemical ionization (APCI)/ion trap mass spectrometry (ITMS) was used
      for the real-time monitoring. The oxidation catalyst was iron oxide type, which
      exponentially reduced trichlorophenol emission. CO emission, however, did not
      show any correlation with the catalyst injection rate. Simultaneous analysis of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) suggested that
      real-time monitoring of trichlorophenol as a surrogate of PCDDs/PCDFs, has a
      potential to timely control the optimum injection rate of PCDD/PCDF suppression
      catalyst continuously and economically.

PMID- 14659950
TI  - Extended bioremediation of PAH/PCP contaminated soils from the POPILE wood
      treatment facility.
AB  - A study was conducted using two pilot-scale land-treatment units (LTUs) to
      evaluate the efficacy of different cultivation and maintenance schedules during
      bioremediation of contaminated soil from a wood treatment facility using
      landfarming technology. The soil contained high concentrations of polycyclic
      aromatic hydrocarbons (PAHs, approximately 13000 ppm) as well as of
      pentachlorophenol (PCP, approximately 1500 ppm). An initial 6-month intensive
      treatment phase was followed by 24 months of less-intensive treatment. During the
      first phase, traditional landfarming practice of regular cultivation was compared
      with a gas-phase composition based cultivation strategy, and both the landfarming
      units were intensively monitored and maintained with respect to moisture control
      and delivery of nutrients. The two strategies resulted in similar contaminant
      concentration profiles with time during this phase, although different microbial
      populations developed in the two-landfarming units. The second (less-intensive)
      treatment phase involved no moisture control and nutrient delivery beyond the
      initial adjustments, and compared natural attenuation (no cultivation) with
      quarterly cultivation of soil. Both the strategies showed similar behavior again.
      GC/MS analysis of the soil samples showed PAH removal including four-ring
      homologues. Leachability tests at zero time and after 6 and 22 months of
      operation showed significant reductions in leaching of PCP and low molecular
      weight PAHs. Extended treatment resulted in some leaching of high molecular
      weight PAHs. Significant biological activity was demonstrated, even at the high
      contaminant concentrations. Phospholipid ester-linked fatty acid (PLFA) analysis
      showed an increase in biomass and a divergence in community composition in soils
      depending on the treatment conducted.

PMID- 14659951
TI  - Model development and application for surfactant biodegradation in an
      acclimatising activated sludge system.
AB  - A model for the biodegradation of non-ionic surfactants in an activated sludge
      system during acclimatisation was developed, based on respirometric and
      titrimetric experimental data. The data were obtained in a sequencing batch
      reactor (SBR) using a non-ionic surfactant as sole carbon source and sludge
      previously acclimatised to a different surfactant. The model was successfully
      applied to successive SBR-cycles of sludge acclimatisation processes subjected to
      two ethoxylated surfactants. The model was validated using the corresponding
      total organic carbon data. The evolution of the model parameters along the
      acclimatisation process was examined. An acclimatisation model was developed
      using the evolution of two of these parameters (affinity constant and inhibition
      constant), supported by two independently calculated acclimatisation indicators.
      This acclimatisation model was then applied to determine an optimal surfactant
      concentration sequence to feed non-acclimatised sludge during a period of 41
      days, in order to induce pre-acclimatisation to this surfactant before it
      replaces another one in the wastewater. The model was also useful in the
      economical assessment of this and alternative procedures to cope with frequent
      changes in activated sludge feed composition.

PMID- 14659952
TI  - PCB and DDT contamination in cultivated and wild sea bass from Ria de Aveiro,
      Portugal.
AB  - Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) and
      metabolites were quantified in muscle and liver of sea bass (Dicentrarchus
      labrax) collected in Ria de Aveiro and in two fish farms. Sea bass from natural
      environment showed lower levels than fish from farming, which may be partly
      attributed to the higher lipid content of cultivated fish. PCB congener
      distribution in tissues of sea bass from the two farms resembled that of diet
      pellets suggesting that commercial diet is a major source of PCBs. However, fish
      in the two sites were fed with diet of similar PCB and DDT contamination but
      showed distinct levels in its tissues not explained by lipid content.

PMID- 14659953
TI  - Environmental exposure to PCBs and cancer incidence in eastern Slovakia.
AB  - In a population-based cross-sectional study, we compared serum levels of 15
      polychlorinated biphenyl (PCB) congeners and three organochlorine pesticides in
      residents of two districts in eastern Slovakia, one with extensive environmental
      contamination from a former PCB production site (Michalovce) and the other
      matched on geography but with low (background) levels (Svidnik). The age-adjusted
      geometric means for sum of 15 measured PCB congeners were statistically
      significantly higher in subjects from the Michalovce district for both sexes:
      3327.6 versus 1331.4 ng/g of lipid in males, 2751.8 versus 992.2 ng/g of lipid in
      females. Levels of DDE and DDT were also significantly higher, although the
      absolute differences were less pronounced. There was no substantial difference in
      HCB levels between the districts. We also conducted an ecologic study to compare
      cancer incidence occurring in these same two districts from 1985 through 1994. We
      calculated standardized incidence ratios (SIRs) and 95% confidence intervals for
      each district using indirect standardization and rates from eastern Slovakia.
      Among males from Michalovce (exposed), but not Svidnik (unexposed), there was an
      excess of cancer of the tongue (SIR=1.46; 1.06-1.96), stomach (SIR=1.15; 1.00
      1.32), lung (SIR=1.14; 1.04-1.24), testis (SIR=1.40; 0.97-1.97), and kidney
      (SIR=1.23; 0.98-1.52), and lower than expected incidence of prostate cancer
      (SIR=0.83; 0.69-0.97); in contrast, there was an excess of peritoneal (SIR=3.05;
      1.11-6.63) and laryngeal cancer (SIR=1.43; 0.99-1.98) in Svidnik not observed
      Michalovce. Among females from Michalovce, but not Svidnik, there was an excess
      of cancer of the lip (SIR=2.54; 1.53-3.96), stomach (SIR=1.22; 1.02-1.44), and
      lung (SIR=1.17; 0.94-1.45); in contrast, there was an excess of kidney (SIR=1.61;
      1.03-2.40) and thyroid (SIR=1.97; 1.12-3.20) cancer in Svidnik not observed in
      Michalovce. Taken together, these results raise the possibility that high
      environmental exposure to organochlorines in the Michalovce district may be
      associated with higher rates of certain cancers, particularly stomach and lung
      cancer.

PMID- 14659954
TI  - Formation of PCDDs and PCDFs during the combustion of polyvinylidene chloride and
      other polymers in the presence of HCl.
AB  - PVDC and three non-chlorinated polymers (PP, PET, and PA) were incinerated at 700
      850 degrees C in a laboratory-scale quartz tubular furnace in the presence of HCl
      (ca. 500 ppm congruent with 0.8 mg/l), and the gas-phase formation of PCDD/Fs,
      their putative precursors and their homologue profiles were investigated. The
      addition of HCl had little or no apparent effect on the level of PCDD/Fs
      formation during PVDC combustion, and their homologue profiles were quite
      different from those of the three non-chlorinated polymers. With PVDC, O8CDD and
      particularly O8CDF were by far most prevalent, apparently as a result of the
      selective formation of the precursors. With each of the three non-chlorinated
      polymers, combustion at 800 degrees C or higher in the presence of HCl resulted
      in PCDD/Fs formation at levels equaling or exceeding those observed with PVDC. In
      trials made with one of them (PP) under the same conditions but using a large
      polymer sample (100 mg vs 20 mg in all other trials), the level of PCDD/Fs
      formation was far higher than with the smaller polymer samples, and thus
      demonstrated the importance of appropriate combustion conditions for polymer
      incineration.

PMID- 14659955
TI  - Comparison of seven indicator PCBs and three coplanar PCBs in beef, pork, and
      chicken fat.
AB  - The risk assessment of polychlorinated biphenyls (PCBs) is difficult since
      complex congeners were used in many industrial applications for a long period of
      time and the residue monitoring in foods of animal origin and the environment
      were not established in comparable systems. The relationships of determined
      concentrations in indicator PCB congeners (mono- and di-ortho PCBs) and coplanar
      PCB congeners (non-ortho PCBs) in livestock products are presented in this study.
      The concentrations of seven indicator PCBs were compared with three coplanar PCBs
      in beef, pork, and chicken fat. Distributions of concentration for the indicator
      PCBs in three different animal species were similar except for that of PCB-118
      (2,3',4,4',5-pentachlorobiphenyl) in pork fat. The congeners with the highest
      concentration were PCB-138 (2,2',3,4,4',5'-hexachlorobiphenyl) in beef and pork
      fat and PCB-28 (2,4,4'-trichlorobiphenyl) in chicken fat. The bioaccumulation and
      metabolism of PCBs in animal species represent different congener profiles in
      livestock products. The percentage of the total concentration of three coplanar
      PCBs was about 2% of the total concentration of the seven indicator PCBs.
      Relatively high concentration of mono-ortho and di-ortho PCBs in fat samples of
      livestock products may be calculated with the concentration of coplanar PCBs that
      can be usually determined on a sequential procedure with dioxin analysis.
      Therefore, the relationship of the amounts between seven indicator PCBs and three
      coplanar PCBs may be useful to derive the composition and level of contaminants
      in beef, pork, and chicken.

PMID- 14659956
TI  - Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans from catalytic
      and thermal oxidizers burning dilute chlorinated vapors.
AB  - Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) have
      been found from 57 field tests on the oxidation of low (a few to a few hundred)
      parts per million levels of chlorinated and non-chlorinated volatile organic
      compounds (VOCs). The oxidation occurs in catalytic oxidizers with platinum,
      platinum/palladium or chromium(IV) oxide combustion catalysts, or in thermal
      oxidizers (without a catalyst). The catalyst inlet temperatures ranged from 293
      to 573 degrees C. The thermal oxidizer operating temperatures (post-flame) were
      from 773 to 927 degrees C. Data of the toxic dioxin and furan isomers are
      reported and also weighted and expressed as international toxic equivalents (TEQ)
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin. The maximum stack emissions, 1.07 ng/m3
      TEQ, occurred at 293 degrees C. Salient results of this field study are: (1) TEQ
      levels in the stack exponentially increase with a decrease in operating
      temperature, an empirical equation is TEQ (ng/dscm)=8.4 exp(-0.0084T degrees C);
      (2) dioxin/furan production occurs at the combustion catalyst; (3) small
      variations in temperature cause large changes in the congener distribution of the
      dioxin and furan isomers; (4) molar TEQ yields from the parent compounds fed to
      the oxidizers are very small (10(-9)-10(-13)); (5) catalytic and thermal
      oxidizers may destroy dioxins fed from the ambient air; and (6) the oxidation of
      chlorinated VOCs with non-chlorinated VOCs reduces emissions of dioxins, likely
      due to the consumption of Cl in producing HCl. Laboratory investigations are
      needed to understand how dioxins are formed (and emitted) under conditions of
      this study.

PMID- 14659957
TI  - Persistent organochlorine compounds in soils and sediments of European high
      altitude mountain lakes.
AB  - The composition of persistent organochlorine compounds (OC) in soils and
      sediments from two high altitude European mountain lakes, Redon in the Pyrenees
      and Ladove in the Tatra mountains, has been studied. Sediment cores from two
      additional lakes in the Tatra mountains, Starolesnianske Pleso and Dlugi Staw,
      have also been examined. DDTs (1.7-13 ng g(-1)) were the most abundant OC in
      soils followed by total polychlorobiphenyls (PCBs; 0.41-1.5 ng g(-1)) and
      hexachlorobenzene (HCB; 0.15-0.91 ng g(-1)). In sediments, the dominant OC were
      also DDTs (3.3-28 ng g(-1)) and PCBs (2.3-15 ng g(-1)). These concentrations are
      low, involving absence of major pollution sources in these high mountain regions.
      The downcore OC profiles in soils and sediments were similar but higher
      concentrations and steeper vertical gradients were observed in the latter.
      Radiometric determinations showed absence of significant OC transport from
      catchment to lake. The sediment-soil difference points therefore to a better
      retention of the OC load in sediments than soils which may be related to the low
      temperatures that are currently encountered at the bottom of the lake water
      column and the depletion of sediment bioturbation in these cold environments.
      Significant qualitative changes in the soil PCB distributions are observed
      downcore. These involve a dominance of the high molecular weight congeners in the
      top core sections and those of lower weight (i.e. less chlorinated) in the
      bottom. Anaerobic dechlorination of higher molecular weight congeners occurring
      in microsites, e.g. as observed in flooded or poorly drained soils, could be
      responsible for these changes. This process could be concurrent to bioturbation.

PMID- 14659958
TI  - Accumulation of polychlorinated biphenyls in sediments of the Venice Lagoon and
      the industrial area of Porto Marghera.
AB  - Sediment cores, collected at seven sites in the Venice Lagoon and within the
      canals of the industrial area were analyzed for polychlorinated biphenyls (PCBs)
      in order to assess the chronology of pollution and its present trends. The
      surficial concentration of PCBs is very high (more than 2049 microg kg(-1)) only
      in the Brentella Canal, probably due to a very recent contaminating episode. Very
      high values downcore (up to 41,639 microg kg(-1)) can be found in different parts
      of the industrial area, especially in the canals Lusore-Brentelle and Salso.
      Lagoon samples are much less contaminated (2.7-123 microg kg(-1)), being
      influenced only occasionally by polluted sediments resuspended from the canals.
      Sediment chronology shows that the delivery of contaminants peaked in the 1970s
      early 1980s, decreasing since at most sites. Congener profiles distinguish PCBs
      in two main categories: heavy congeners characterize a baseline pollution,
      probably due to a large variety of sources within the lagoon system, whereas a
      mixture of light PCBs was discharged into the canals Brentella and Salso.

PMID- 14659959
TI  - Acclimation of anaerobic sludge degrading chlorophenols and the biodegradation
      kinetics during acclimation period.
AB  - The acclimation of sludge from Hangzhou citrate factory and Hangzhou municipal
      wastewater treatment plant for degradation dechlorination of chlorophenols (CPs)
      compounds, and its biodegradation kinetics were studied in batch process with or
      without addition of sucrose. Three monochlorophenols (2-CP; 3-CP; 4-CP) and
      pentachlorophenol (PCP) were concurrently fed to different bioreactors. The
      parameters that were monitored included biogas production, biogas composition and
      chemical oxygen demand (COD). The results showed that acclimation with
      chlorophenol can increase the degradation activity of anaerobic sludge and
      degradation rate of chlorophenolic compounds, and reduce the lag time.
      Degradation dechlorination activity of the acclimated sludge strongly depended on
      sludge source, microorganism population and chlorophenol congener. 2-CP was more
      easily acclimated than 3-CP and 4-CP. Among the four tested compounds, 4-CP was
      the most difficult to be acclimated. The observed degradation rate with presence
      of sucrose was higher than that with absence of sucrose, suggesting that addition
      of the external carbon source can stimulate the formation of acclimated sludge
      which could effectively degrade chlorophenols. Kinetic equations of
      biodegradation of chlorophenols were also presented in this paper.

PMID- 14659960
TI  - Impurity of recombinant adeno-associated virus type 2 affects the transduction
      characteristics following subretinal injection in the rat.
AB  - We recently reported that different purification methods of recombinant adeno
      associated virus type 2 (rAAV2) affect the transduction characteristics following
      subretinal injection. In this study, we examined the roles of contaminant
      proteins from the HEK-293 cells and helper adenovirus, inactivation of helper
      adenovirus and cell stress induced by DNA-damaging agents in rAAV-mediated
      retinal transduction. Our results showed that contaminating factors/proteins
      resulting from the helper E1 deleted adenovirus are possibly responsible for
      efficient RPE transduction. Future studies of these factors will undoubtedly lead
      to development of new therapeutic approaches to PR- and RPE-specific retinal
      diseases.

PMID- 14659961
TI  - Intravitreal triamcinolone does not alter basal vascular endothelial growth
      factor mRNA expression in rat retina.
AB  - Intravitreal triamcinolone inhibits choroidal neovascularization. To investigate
      if vascular endothelial growth factor (VEGF) is affected, we examined VEGF
      expression after intravitreal triamcinolone administration in rat retina. Using
      in situ hybridization, we have found dense clustered VEGF mRNA signals in the
      retinal pigment epithelium, moderate patchy signals in the inner nuclear layer,
      and positive labeling in a sub-population of ganglion cells. Densitometry and
      northern blot analysis revealed no significant alteration of VEGF mRNA expression
      pattern and level 3-21 days after triamcinolone injection. Our data indicate that
      intravitreal triamcinolone does not affect basal VEGF mRNA expression in normal
      adult rat retina.

PMID- 14659962
TI  - Temporal dependence of local motion induced shifts in perceived position.
AB  - It has been shown that a moving visual pattern can influence the perceived
      position of outlying, briefly flashed objects. Using a rotating bar as an
      inducing stimulus we observed a shift, in the direction of motion, of the
      perceived position of small bars flashed together on either side of the moving
      bar. The greatest shift occurred when the 13 ms flashes were presented 60 ms
      before the rotating bar came closest to their locations. By varying rotation
      speed we showed that the peak effect was determined by the temporal rather than
      the spatial interval. The motion induced shift could be attenuated by introducing
      background flickering dots. The perceived shift decreased with distance from
      motion when the eccentricity of the flashes was kept constant. We conclude that
      the shift reflects feedback to primary visual cortex from motion selective cells
      in extrastriate cortex with receptive fields that overlap the retinal location of
      the flash.

PMID- 14659963
TI  - The role of a local reference in stereoscopic detection of depth relief.
AB  - Stereoacuity thresholds have been shown to depend on the disparity of a point
      with respect to a slanted reference plane through neighbouring points [Curr.
      Biol. 12 (2002) 825]. Here we explored a wider range of conditions, including
      slanting the reference points about a horizontal axis and varying the spacing of
      the reference dots, allowing alternative hypotheses for the effect to be
      distinguished. The stimulus consisted of three dots; the outer two defined a line
      that was slanted in depth. Observers judged in which of two intervals the third,
      central dot was displaced from the location midway between the outer reference
      dots. The displacement consisted of both a disparity and a shift in the fronto
      parallel plane. We compared performance for pairs of conditions in which the
      disparity was the same but the fronto-parallel shifts were in opposite
      directions. Models based purely on relative disparity predict that performance
      should be the same for these conditions. We found consistent differences:
      performance was always better when the target had a greater disparity with
      respect to the line joining the reference dots. The other stimulus parameters
      varied were: target disparity (concave/convex), stimulus size (large/small),
      slant sign (sky/ground) and axis (vertical/horizontal). The results suggest that
      either (a) disparity with respect to the line drawn through the outer reference
      dots or (b) difference in disparity gradients on either side of the target
      determines the depth discrimination threshold for these stimuli.

PMID- 14659964
TI  - Unveiling the foveal blue scotoma through an afterimage.
AB  - The absence of short-wave-sensitive (S-) cones in the human foveola normally goes
      unnoticed, but the resulting foveal S-cone, or blue, scotoma can be visualized as
      the negative afterimage of a short-wavelength adapting field on a larger white
      background. The afterimage has an annular shape with a lighter inner region that
      corresponds to Maxwell's spot, and a small bright spot in the center
      corresponding to the foveal blue scotoma. We have shown that the visibility of
      the center spot in the afterimage approximately follows the spectral sensitivity
      curve of the S-cones. We further demonstrate that the central bright spot
      subtends a retinal area that is coincident with the tritanopic region of the
      foveola. The macular pigment distribution measured for the same observers also
      peaks in the central fovea, but has a relatively high density over a broader
      retinal region than the bright spot in the negative afterimage, and more closely
      corresponds to the lighter annular region of the afterimage. The results support
      the hypothesis of an active post-receptoral process for filling-in of chromatic
      scotomas.

PMID- 14659965
TI  - Recognizing and segmenting objects in clutter.
AB  - When viewing a cluttered scene, observers may not be able to segment whole
      objects prior to recognition. Instead, they may segment and recognize these
      objects in a piecemeal way. Here we test whether observers can use the appearance
      of one object part to predict the location and appearance of other object parts.
      During several training sessions, observers studied an object against a blank
      background. They then viewed this object against a background of clutter that
      camouflaged some parts of the object while leaving other parts salient. The
      observer's task was to find the camouflaged part. We varied the symmetry of the
      salient part with the expectation that as this symmetry decreased, the
      information about the camouflaged part's location and appearance would increase
      and this would facilitate search. Our results suggest that observers can use the
      salient part to predict the location, but not the appearance, of the camouflaged
      part.

PMID- 14659966
TI  - Changes in ocular torsion position produced by a single visual line rotating
      around the line of sight--visual "entrainment" of ocular torsion.
AB  - A large- or full-field visual stimulus slowly rotating around the naso-occipital
      axis of an observer causes both eyes to tort, and many of the factors controlling
      this optokinetic torsional response have been identified. The present study
      reports that a single line rotating about the line of sight can cause both eyes
      to tort in the same direction as the stimulus but with a low gain. We have used
      the term 'entrainment' to describe this torsional response. This paper reports
      some of the factors associated with entrainment. Video measures of 3-d eye
      position were recorded while the subject made settings of a simple visual line to
      subjective visual horizontal (SVH) and vertical (SVV) using the standard method
      of-adjustment paradigm. The visual line was composed of 11 light-emitting diodes;
      the line subtended a visual angle of 19 degrees, and moved at a constant speed of
      4.8 degrees /s. Settings were made in an otherwise darkened room, and also in the
      light. Subjects were required to maintain fixation of the central LED while
      making settings from starting positions 10 or 20 degrees either side of
      gravitational horizontal or vertical. We show that entrainment of ocular torsion
      by the single moving visual line is low in gain but a reliable and repeatable
      effect and that (1) there are considerable individual differences between
      subjects but within-subject consistency, (2) all subjects show larger and more
      consistent torsional entrainment for lines moving to SVH than lines moving to
      SVV, (3) the strongest entrainment generally occurs within about 10 degrees of
      the target position, and (4) entrainment is also present in the light, though
      with slightly reduced gain.

PMID- 14659967
TI  - Natural image profiles are most likely to be step edges.
AB  - We introduce Geometric Texton Theory (GTT), a theory of categorical visual
      feature classification that arises through consideration of the metamerism that
      affects families of co-localised linear receptive-field operators. A refinement
      of GTT that uses maximum likelihood (ML) to resolve this metamerism is presented.
      We describe a method for discovering the ML element of a metamery class by
      analysing a database of natural images. We apply the method to the simplest case-
      the ML element of a canonical metamery class defined by co-registering the
      location and orientation of profiles from images, and affinely scaling their
      intensities so that they have identical responses to 1-D, zeroth- and first
      order, derivative of Gaussian operators. We find that a step edge is the ML
      profile. This result is consistent with our proposed theory of feature
      classification.

PMID- 14659968
TI  - Evidence against age-related enlargements of ganglion cell receptive field
      centers under scotopic conditions.
AB  - Age-related changes in the neural organization of spatial information are
      required to account for much of the senescent loss in human scotopic spatial
      vision, specifically declines in the high spatial frequency cut-off of the
      contrast sensitivity function and enlargements of the area over which there is
      complete spatial summation (Ricco's area). These results are consistent with
      hypothesized enlargements of ganglion cell receptive field centers during
      adulthood. This hypothesis was tested with 50 subjects (19-88 years) by measuring
      contrast thresholds for two low spatial frequency gratings (0.3 and 1.2 cycles
      per degree) at a series of scotopic mean illuminance levels. Contrast sensitivity
      increased with retinal illuminance and then reached a plateau, corresponding to
      the onset of Weber-like behavior. No age-related change in the light level
      associated with the onset of Weber-like behavior was found at either spatial
      frequency. This result is inconsistent with proposed age-related enlargements of
      ganglion cell receptive field centers under scotopic conditions.

PMID- 14659969
TI  - Multiple molecular and neuropharmacological effects of MDMA (Ecstasy).
AB  - 3,4-Methylenedioxymethamphetamine (MDMA), commonly referred to as Ecstasy, is a
      widely abused, psychoactive recreational drug, which induces short- and long-term
      neuropsychiatric behaviors. This drug is neurotoxic to serotonergic neurons in
      vivo, and induces programmed cell death in cultured human serotonergic cells and
      rat neocortical neurons. Over the years it has been shown that MDMA alters the
      release of several neurotransmitters in the brain, it induces recompartmentation
      of intracellular serotonin and c-fos, and modifies the expression of a few genes.
      Recently, we observed changes in gene expression in mice treated with MDMA, and
      cloned and sequenced 11 cDNAs thus affected (4 correspond to known and 7 to
      unknown genes). The effect of MDMA on two of these genes, GABA transporter 1 and
      synaptotagmin IV was studied in detail. Characterization of the relationship
      between a given gene and certain physiological or behavioral effects of MDMA
      could shed light on the mechanism of the drug's action. However, establishing
      such a connection is difficult for several reasons, including that serotonergic
      neurons are not the only cells affected by MDMA. In this review, molecular and
      neurochemical events that occur in the brain following exposure to MDMA, and link
      between the observed molecular changes with known physiological effects of the
      drug are discussed. It is indicated that MDMA alters the expression of several
      proteins involved in GABA neurotransmission, thus having critical effect on
      thermoregulation and MDMA acute toxicity. This analysis should facilitate
      development of novel approaches to prevent deleterious effects, especially
      mortality induced by MDMA and other abused psychostimulants.

PMID- 14659970
TI  - A role for calcium/calmodulin kinase in insulin stimulated glucose transport.
AB  - Previous research has shown that the CAMK (calcium/calmodulin dependent protein
      kinase) inhibitor, KN62, can lead to reductions in insulin stimulated glucose
      transport. Although controversial, an L-type calcium channel mechanism has also
      been hypothesized to be involved in insulin stimulated glucose transport. The
      purpose of this report was to determine if 1) L-type calcium channels and CAMK
      are involved in a similar signaling pathway in the control of insulin stimulated
      glucose transport and 2) determine if insulin induces an increase in CAMKII
      phosphorylation through an L-type calcium channel dependent mechanism. Insulin
      stimulated glucose transport was significantly (p<0.05) inhibited to a similar
      extent ( approximately 30%) by both KN62 and nifedipine in rat soleus and
      epitrochelaris muscles. The new finding of these experiments was that the
      combined inhibitory effect of these two compounds was not greater than the effect
      of either inhibitor alone. To more accurately determine the interaction between
      CAMK and L-type calcium channels, we measured insulin induced changes in CAMKII
      phosphorylation using Western blot analysis. The novel finding of this set of
      experiments was that insulin induced an increase in phosphorylated CAMKII (
      approximately 40%) in rat soleus muscle that was reversed in the presence of KN62
      but not nifedipine. Taken together these results suggest that a CAMK signaling
      mechanism may be involved in insulin stimulated glucose transport in skeletal
      muscle through an L-type calcium channel independent mechanism.

PMID- 14659971
TI  - CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic
      subjects.
AB  - Previous studies suggested that the onset of phenytoin-induced gingival
      overgrowth depended on serum phenytoin concentration. Cytochrome P450 2C (CYP2C)
      plays an important role in phenytoin metabolism. Recently, single nucleotide
      polymorphisms in the coding region of CYP 2C influencing phenytoin metabolism
      were identified. The purpose of the present study was to see if CYP 2C
      polymorphisms might relate to the onset and severity of phenytoin-induced
      gingival overgrowth. Twenty-eight epileptic patients taking phenytoin aged 15 to
      75 (mean age: 42.2 years old, 20 males and 8 females) and 56 unrelated healthy
      subjects aged 30 to 48 (mean age: 36.8 years old, 48 males and 8 females) were
      examined for CYP 2C polymorphisms. All epileptic subjects were examined for the
      degree of gingival overgrowth, daily phenytoin dose and serum phenytoin
      concentration. The results indicated about 7% of the subjects including epileptic
      and healthy subjects examined were positive for CYP 2C9*3. However, the degree of
      gingival overgrowth did not directly correlate with CYP 2C polymorphisms.
      Nevertheless, the subjects with severer gingival overgrowth exhibited
      significantly higher serum phenytoin concentration, indicating that phenytoin
      metabolism is an important determinant for the severity of the disease.
      Additionally, CYP 2C9*3 carriers exhibited significantly higher serum drug
      concentration to drug dose. Therefore, we concluded although the gene analysis is
      not directly related to diagnose the disease itself, it can be utilized in
      estimating serum phenytoin concentration from drug dose, which in turn serves to
      predict the future development and clinical course of the disease.

PMID- 14659972
TI  - 2', 3'-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T
      lymphoid cells.
AB  - In vitro culture of H9 human lymphoid cells in the presence of 5.0 microM
      dideoxycytidine (ddC), for about 40-45 days, selected cells (H9-ddC cells), which
      were resistant to the drug and cross-resistant to AZT (zidovudine) and 5-fluoro
      2'-deoxyuridine (FdUR). The major mechanism of cross-resistance to AZT and FdUR
      in these cells was low cellular activity of thymidine kinase (TK). To explore
      molecular mechanisms of the reduced TK activity in H9-ddC cells, the mRNA
      expression of TK1 and TK2 and western blot analysis of TK1 protein were
      performed. RT-PCR analysis revealed that in H9-ddC cells the expression of both
      TK1 and TK2 mRNA was reduced to 27.1% and 79.4%, respectively. The reduced TK1
      gene expression was confirmed by an absence of a detectable TK1 protein band in
      western blot of H9-ddC cells. These results demonstrate that long-term treatment
      of H9 cells in the presence of ddC down-regulated TK1 and TK2 gene expression and
      reduced the expression and activity of TK in the resistant cells.

PMID- 14659973
TI  - Comparison of in vitro selectivity profiles of solifenacin succinate (YM905) and
      current antimuscarinic drugs in bladder and salivary glands: a Ca2+ mobilization
      study in monkey cells.
AB  - We investigated the effects of the new muscarinic receptor antagonist solifenacin
      succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4
      tetrahydroisoquinoline-2-carboxylate monosuccinate] and the current
      antimuscarinic drugs for the treatment of overactive bladder (oxybutynin,
      tolterodine and darifenacin) on intracellular Ca(2+) mobilization in response to
      M(3) muscarinic receptor activation in bladder smooth muscle and submandibular
      gland cells isolated from Cynomolgus monkeys. Solifenacin concentration
      dependently inhibited carbachol-induced Ca(2+) mobilization, with affinity
      constant values (pKi) of 8.5 +/- 0.053 in bladder smooth muscle cells and 8.2 +/-
      0.051 in submandibular gland cells (n = 5). The pKi value of solifenacin was
      almost equivalent to the values of oxybutynin, tolterodine and darifenacin in
      bladder smooth muscle cells (8.7, 8.5 and 8.4, respectively), while being lower
      than those in submandibular gland cells (9.0, 8.7 and 8.8, respectively). The
      bladder-selectivity index (Ki ratio: submandibular gland/bladder) for solifenacin
      (2.1) was statistically higher, moreover, than those for oxybutynin, tolterodine
      and darifenacin (0.51, 0.65 and 0.46, respectively). These findings consequently
      indicate solifenacin's unique profile in terms of its selectivity for bladder
      smooth muscle cells over salivary gland cells in non-human primates, relative to
      oxybutynin, tolterodine and darifenacin. Solifenacin may, therefore, confer a
      promising therapeutic advantage for reducing adverse effects, such as dry mouth,
      exhibited by current antimuscarinic therapy for overactive bladder.

PMID- 14659974
TI  - Pycnogenol, French maritime pine bark extract, improves endothelial function of
      hypertensive patients.
AB  - A placebo-controlled, double-blind, parallel group study was performed with 58
      patients to investigate effects of French maritime pine bark extract, Pycnogenol,
      on patients with hypertension. Supplementation of the patients with 100 mg
      Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium
      antagonist nifedipine in a statistically significant manner. The intake of
      Pycnogenol decreased endothelin-1 concentrations significantly compared to
      placebo while concentrations of 6-keto prostaglandin F1a in plasma were
      significantly higher compared to placebo. Values for nitric oxide (NO) in plasma
      increased in both groups, but the differences were not significant. Angiotensin
      II concentrations in plasma were lowered in the placebo group to a larger extent
      than in the Pycnogenol group. Heart rate, electrolytes and blood urea nitrogen
      were not changed during treatment in both groups of patients. Unwanted effects
      observed in both groups were of mild and transient nature, such as
      gastrointestinal problems, vertigo, headache and nausea. Differences in rate of
      side effects were not statistically significant between the two groups. Study
      results support a supplementation with Pycnogenol for mildly hypertensive
      patients.

PMID- 14659975
TI  - Expression of vascular endothelial growth factor (VEGF) and its cognate receptors
      in human pheochromocytomas.
AB  - Pheochromocytomas are well-vascularized tumors, suggesting that a potent
      angiogenic factor may be involved in the mechanism of their formation. As
      vascular endothelial growth factor (VEGF) is a potent mitogen for vascular
      endothelial cells, here we have investigated the mRNA and protein expression of
      VEGF and the mRNA expression of its two receptors (Flt-1 and Flk-1/KDR) in
      pheochromocytomas tissue. An increase in VEGF mRNA (mainly isoforms VEGF(121) and
      VEGF(165)) and in VEGF protein expression were observed by semi-quantitative RT
      PCR and Western blot, respectively, compared to normal adrenomedullary tissue.
      Flk-1/KDR, and Flt-1 levels of mRNA were also increased markedly in tumors and
      correlated with levels of VEGF mRNA. Therefore, we speculate that upregulation of
      VEGF expression and its receptors might be important in the pathogenesis of
      pheochromocytomas.

PMID- 14659976
TI  - Mucosal damage induced by preferential COX-1 and COX-2 inhibitors: role of
      prostaglandins and inflammatory response.
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) are well known to induce gastric
      mucosal damage including bleeding, ulceration and perforation in humans and
      animals too. These effects are related with the inhibition of the enzyme
      cyclooxygenase, which is the main established mechanism of action for these
      drugs. Fasted rats were given piroxicam, preferential COX-1 inhibitor (10-20
      mg/kg) or meloxicam, preferential COX-2 inhibitor (7.5-15 mg/kg) orally. Six or
      nine hours (h) later, respectively, the stomach was excised, the severity of the
      damage assessed and myeloperoxidase (MPO) activity measured, as well as
      prostaglandin PGE(2) content. Furthermore, in order to assess the effects of
      these oxicams over previously damaged gastric mucosa, 1 ml of 0.6 N HCl was
      administered p.o. followed, 1 h after, of the correspondent dose of each NSAID,
      and the same parameters were determined. Oral administration of both drugs dose
      dependently caused acute gastric haemorrhage erosions. Myeloperoxidase activity
      was significantly increased by piroxicam administration. In addition, PGE(2)
      content was significantly reduced. The association between the administration of
      the acid and NSAID caused a worsening of the damage and, while myeloperoxidase
      activity did not modify by both piroxicam and meloxicam, PGE(2) levels were
      reduced. These results suggest that the PG derived from both COX-1 and COX-2
      pathway plays a beneficial role in the gastroprotection, and thus caution should
      be exercise in the clinical use of preferential COX-2 inhibitors.

PMID- 14659977
TI  - Induction of CYP1A by a diterpene quinone tanshinone IIA isolated from a
      medicinal herb Salvia miltiorrhiza in C57BL/6J but not in DBA/2J mice.
AB  - Effects of tanshinone IIA, an active diterpene quinone of the herbal medicine
      Salvia miltiorrhiza (Danshen), on cytochrome P450 (CYP), UDP-glucuronosyl
      transferase (UGT), and glutathione S-transferase (GST) were studied in the
      arylhydrocarbon (Ah)-responsive C57BL/6J (B6) and nonresponsive DBA/2J (D2) mice.
      Oral treatment of tanshinone IIA caused a dose-dependent increase of liver
      microsomal 7-methoxyresorufin O-demethylation (MROD) activity in B6 but not in D2
      mice. In B6 mice, tanshinone IIA increased hepatic benzo(a)pyrene hydroxylation
      (AHH), 7-ethoxyresorufin O-deethylation, MROD, and 7-ethoxycoumarin O
      deethylation activities. The levels of Cyp1A2 protein and mRNA were elevated. On
      the contrary, in D2 mice, tanshinone IIA decreased hepatic AHH and nifedipine
      oxidation activities and the CYP3A protein level without affecting other
      activities determined. Cyp1A2 protein and mRNA levels were not affected by
      tanshinone IIA in D2 mice. Tanshinone IIA had no effects on UGT and GST
      activities in both B6 and D2 mice. These results demonstrated that induction of
      CYP1A2 by tanshinone IIA depended on the Ah-responsiveness and occurred at pre
      translational level.

PMID- 14659978
TI  - Antioxidant and antiapoptotic activities of idoxifene and estradiol in hepatic
      fibrosis in rats.
AB  - Oxidative stress plays a causative role in the development of hepatic fibrosis
      and apoptosis. Estradiol (E2) is an antioxidant, and idoxifene is a tissue
      specific selective estrogen receptor modulator. We have previously demonstrated
      that E2 inhibits hepatic fibrosis in a rat model of hepatic fibrosis induced with
      dimethylnitrosamine (DMN), and suppresses activation of the nuclear factor (NF)
      kappaB proinflammatory transcription factor in cultured rat hepatocytes
      undergoing oxidative stress. This study reports on the antioxidant and
      antiapoptotic role of idoxifene and E2 in the DMN model of hepatic fibrosis. The
      DMN model rats were administered with idoxifene or E2, and were examined activity
      of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and expression of
      Bcl-2 family proteins in the liver. During the course of hepatofibrogenesis after
      DMN treatment, serum levels of lactate dehydrogenase (LDH), a biomarker for
      necrosis, and hepatic levels of malondialdehyde (MDA), an end product of lipid
      peroxidation, increased rapidly for 3 days. On day 14, serum LDH levels
      normalized, and hepatic fibrosis developed with increased levels of MDA and
      collagen and decreased production of SOD and GPx in the liver. Fibrotic liver
      also showed downregulation of Bcl-2 and Bcl-X(L) expression and upregulation of
      Bad expression. Idoxifene and E2 suppressed DMN-mediated necrosis, lipid
      peroxidation, the loss of antioxidant enzyme activity, and proapoptotic status in
      Bcl-2 family protein expression as well as hepatic fibrosis. These findings
      indicate that, in addition to their antiinflammatory and antifibrotic action,
      idoxifene and E2 could enhance antioxidant and antiapoptotic activity in hepatic
      fibrosis in rats.

PMID- 14659979
TI  - Effect of thymol on calcium handling in mammalian ventricular myocardium.
AB  - Concentration-dependent effects of thymol on calcium handling were studied in
      canine and guinea pig cardiac preparations (Langendorff-perfused guinea pig
      hearts, canine ventricular trabeculae, canine sarcoplasmic reticular vesicles and
      single ryanodine receptors). Thymol induced a concentration-dependent negative
      inotropic action in both canine and guinea pig preparations (EC(50) = 297 +/- 12
      microM in dog). However, low concentrations of thymol reduced intracellular
      calcium transients in guinea pig hearts without decreasing contractility. At
      higher concentrations both calcium transients and contractions were suppressed.
      In canine sarcoplasmic reticular vesicles thymol induced rapid release of calcium
      (V(max) = 0.47 +/- 0.04 nmol s(-1), EC(50) = 258 +/- 21 microM, Hill coefficient
      = 3.0 +/- 0.54), and decreased the activity of the calcium pump (EC(50) = 253 +/-
      4.7 microM, Hill coefficient = 1.62 +/- 0.05). Due to the less sharp
      concentration-dependence of the ATPase inhibition, this effect was significant
      from 50 microM, whereas the thymol-induced calcium release only from 100 microM.
      In single ryanodine receptors incorporated into artificial lipid bilayer thymol
      induced long lasting openings, having mean open times increased with 3 orders of
      magnitude, however, the specific conductance of the channel remained unaltered.
      This effect of thymol was not voltage-dependent and failed to prevent the binding
      of ryanodine. In conclusion, the negative inotropic action of thymol can be
      explained by reduction in calcium content of the sarcoplasmic reticulum due to
      the combination of the thymol-induced calcium release and inhibition of the
      calcium pump. The calcium-sensitizer effect, observed at lower thymol
      concentrations, indicates that thymol is likely to interact with the contractile
      machinery also.

PMID- 14659980
TI  - Effect of Y-24180 on Ca2+ movement and proliferation in renal tubular cells.
AB  - In canine renal tubular cells, the effect of Y-24180, a presumed specific
      platelet activating factor (PAF) receptor antagonist, on intracellular Ca(2+)
      concentration ([Ca(2+)](i)) was measured by using fura-2 as a Ca(2+)-sensitive
      fluorescent probe. Y-24180 (0.1-10 microM) caused a rapid and sustained
      [Ca(2+)](i) rise in a concentration-dependent manner. The [Ca(2+)](i) rise was
      prevented by 30% by removal of extracellular Ca(2+), but was not changed by
      dihydropyridines, verapamil and diltiazem. Y-24180-induced Ca(2+) influx was
      confirmed by Mn(2+)-influx induced quench of fura-2 fluorescence. In Ca(2+)-free
      medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase,
      caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of 5
      microM Y-24180 on [Ca(2+)](i) was abolished; conversely, depletion of Ca(2+)
      stores with 5 microM Y-24180 abolished thapsigargin-induced [Ca(2+)](i) rise.
      U73122, an inhibitor of phoispholipase C, inhibited ATP-, but not Y-24180-induced
      [Ca(2+)](i) rise. Overnight treatment with Y-24180 did not alter cell
      proliferation rate. Collectively, these results suggest that Y-24180 acts as a
      potent, but not cytotoxic, Ca(2+) mobilizer in renal tubular cells, by
      stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release.
      Since alterations in Ca(2+) movement may interfere many cellular signaling
      processes unrelated to modulation of PAF receptors, caution must be applied in
      using this chemical as a selective PAF receptor antagonist.

PMID- 14659981
TI  - Less medication switching after initial start with atypical antipsychotics.
AB  - We investigated the extent and time of switching to another oral antipsychotic in
      newly admitted in-patients that started oral antipsychotic therapy. In a
      retrospective follow-up study of 522 newly admitted patients who started with an
      oral antipsychotic, we applied a case-control analysis considering patients
      switching to another oral antipsychotics as cases. Association between patient
      characteristics and switching antipsychotic medication was evaluated using
      logistic regression analysis. A Kaplan-Meier plot was performed to analyse time
      to switch. Patients initially treated with an oral typical antipsychotic showed a
      twofold increased risk to switch to another antipsychotic compared to patients
      treated with an oral atypical antipsychotic (adjusted OR=1.79 95% CI=1.15-2.78).
      The Kaplan-Meier survival analysis revealed that patients started with a typical
      antipsychotic switched sooner compared to patients on atypical antipsychotics.
      Atypical antipsychotics are less frequently associated with switching in
      comparison with typical antipsychotics suggesting overall better treatment
      satisfaction.

PMID- 14659982
TI  - Sub-chronic treatment with an extract of Hypericum perforatum (St John's wort)
      significantly reduces cortisol and corticosterone in the rat brain.
AB  - Extracts of Hypericum perforatum (HP) have been shown to be effective for the
      treatment of mild to moderate depression. Its mode of action has not been fully
      elucidated. An increase in plasma and cerebrospinal fluid (CSF) cortisol is
      frequently observed in depression. Studies have suggested that HP might alter
      brain cortisol and corticosterone through its effect on multidrug transporter
      glycoprotein (Pgp). We investigated the effect of sub-chronic treatment with an
      extract of HP (LI 160) on brain levels of corticosterone and cortisol in the rat.
      Results show that HP significantly reduced corticosterone and cortisol in brain
      frontal cortex tissue. These changes are not reflected in serum. These findings
      may be important with respect to HPs mode of antidepressant action.

PMID- 14659984
TI  - Paroxetine influences respiration in rats: implications for the treatment of
      panic disorder.
AB  - Since hyperventilation and shortness of breath are characteristic features of
      panic attacks, and since the attacks can be elicited by CO(2) inhalation, an
      involvement of central or peripheral chemoreceptors in the pathophysiology of
      panic disorder has been suggested. Prompted by clinical reports suggesting that
      the susceptibility to spontaneous as well as CO(2)-induced anxiety and
      hyperventilation is attenuated by serotonin reuptake inhibitors (SRIs), we
      undertook the present study in order to explore the possible effect of an SRI,
      paroxetine, on baseline respiration and CO(2)-induced hyperventilation in freely
      moving Wistar rats. A significant increase in baseline respiratory rate was seen
      both after 5 and 15 weeks of treatment with paroxetine. CO(2) exposure induced a
      dose-dependent increase in respiratory rate, but not tidal volume, in both
      paroxetine-treated rats and controls; this response was reduced after 15 weeks of
      paroxetine treatment, but not after 5 weeks of treatment. We suggest that an
      influence on the regulation of respiration may be of importance for the anti
      panic effect of SRIs.

PMID- 14659983
TI  - International consensus statement on attention-deficit/hyperactivity disorder
      (ADHD) and disruptive behaviour disorders (DBDs): clinical implications and
      treatment practice suggestions.
AB  - Researchers and clinicians worldwide share concerns that many youngsters with
      attention-deficit/hyperactivity disorder (ADHD) and/or disruptive behaviour
      disorders (DBDs) do not receive appropriate treatment despite availability of
      effective therapies. At the request of Johnson and Johnson (sponsor), 11
      international experts in child and adolescent psychiatry were selected by
      Professor Stan Kutcher (chair) to address these concerns. This paper describes
      the experts' consensus conclusions, including treatment practice suggestions for
      physicians involved in the early treatment of youngsters with ADHD (or
      hyperkinetic disorder, in countries preferring this classification) and/or DBDs
      internationally: suggested first-line treatment for ADHD without comorbidity is
      psychostimulant medication aided by psychosocial intervention. For ADHD with
      comorbid conduct disorder (CD), psychosocial intervention combined with
      pharmacotherapy is suggested. For primary CD, suggested first-line treatment is
      psychosocial intervention, with pharmacotherapy considered as an 'add-on' when
      aggression/impulsivity is marked and persistent. Pharmacotherapy requires careful
      titration; full-day coverage is the suggested goal. Regular long-term follow-up
      is recommended.

PMID- 14659985
TI  - Smoking impact on CYP1A2 activity in a group of patients with schizophrenia.
AB  - The purpose of the present study was to assess the impact of smoking on the
      metabolism of psychotropic drugs in a group of patients with schizophrenia, by
      measuring CYP1A2 activity. This activity was assessed by the molar ratio (MR) of
      caffeine metabolites in urine [(AFMU+1U+1X)/17U] and saliva (17X/137X).
      Participants were 40 patients with schizophrenia: 30 current cigarette smokers
      and 10 nonsmokers. The two groups (smokers and nonsmokers) differed significantly
      in their ratio of men to women (83% men and 17% women were among smokers compared
      with 50% men and 50% women nonsmokers). No other group differences were found
      regarding age, level of education, PANSS, extrapyramidal symptoms, age of
      symptoms onset, antipsychotic doses (chloropromazine equivalents), and
      anticholinergic drug used. Smokers had significant higher MR in urine (P<0.001)
      as well as in saliva (P=0.001) than nonsmokers, suggesting a higher activity of
      CYP1A2 dependent on smoking. When gender was used as a covariate, the differences
      between the two groups remained significant for MR. Cigarette smoking may be a
      factor influencing the plasma levels of antipsychotics that metabolized through
      CYP1A2. Clinicians should weight the possibility that smoking and the subsequent
      modulation of antipsychotic metabolism may be the main reason of treatment
      resistance. Furthermore, any attempt to reduce or cease smoking in patients with
      schizophrenia necessitates close monitoring of drug doses, because untoward
      adverse effects may emerge.

PMID- 14659986
TI  - Analysis of freezing behavior and ultrasonic vocalization in response to foot
      shocks, ultrasound signals and GABAergic inhibition in the inferior colliculus:
      effects of muscimol and midazolam.
AB  - Freezing behavior is a common response to distal threatening stimuli. It has been
      reported that experimenter-presented 20-kHz tones produce freezing in Wistar
      rats. The present studies were designed to determine the acoustic specificity for
      induction of the emission of ultrasound vocalizations (USV) and freezing of rats
      to either ultrasound tones or to a standard stressor, foot-shocks. We also
      examined whether GABA-benzodiazepine mechanisms, known for modulating anxiety
      related processes, are involved in the regulation of defensive responses to these
      two aversive unconditioned stimuli. It was found that emission of USV was only
      observed with foot-shocks. Moreover, rats exhibited freezing when they were
      exposed to foot-shocks and 20-25-kHz ultrasound signals. Likewise, removal of the
      GABAergic inhibitory control on the neural substrates of aversion in the inferior
      colliculus by local microinjections of semicarbazide, a blocker of the glutamic
      acid decarboxylase, caused freezing behavior without emission of USV. All these
      responses were significantly reduced by midazolam and muscimol. It is suggested
      that the neural substrates of aversion in the inferior colliculus are under
      inhibitory control of GABAergic mechanisms and are different from those triggered
      by foot-shocks.

PMID- 14659987
TI  - Serotonin transporter promoter gene polymorphic region (5-HTTLPR) and personality
      in female patients with seasonal affective disorder and in healthy controls.
AB  - Serotonergic pathways have been related to altered personality patterns in
      seasonal affective disorder (SAD). The short allele (s) of a polymorphism in the
      serotonin transporter promoter gene (5-HTTLPR) has been associated with
      neuroticism and anxiety-related personality traits in healthy volunteers. We
      investigated personality and 5-HTTLPR in female SAD patients using the
      Temperament and Character Inventory (TCI). TCI was completed by 56 female
      patients and 76 age-matched female controls. DNA was genotyped using polymerase
      chain reaction methods. Subjects homozygous for the long allele (l) were compared
      to s carriers. Females with SAD had higher scores in Harm Avoidance and lower
      scores in Novelty Seeking, Self-Directedness and Cooperativeness when compared to
      controls. Patients carrying the s allele had lower Self-Directedness scores. Our
      data indicate that females with SAD show altered personality traits. The s allele
      was associated with lower Self-Directedness scores in SAD patients, whereas there
      were no significant differences in TCI dimensions between patients and controls
      in carriers of the long allele.

PMID- 14659988
TI  - GABAergic system and imipramine-induced impairment of memory retention in rats.
AB  - In this study, the influence of GABAergic agents, imipramine and their
      interactions on memory retention have been investigated. Intracerebroventricular
      (i.c.v.; 1-6 microg/rat) or intraperitoneal (i.p.; 5-40 mg/kg) injection of
      imipramine decreased memory retention. i.c.v. administration of GABA receptor
      agonists baclofen and muscimol also reduced memory retention. The combination of
      i.p. or i.c.v. injection of imipramine with a low dose of muscimol (1 microg/rat,
      i.c.v.) induced a higher decrease in memory retention. The higher dose of GABA(B)
      receptor antagonist CGP35348 [p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid]
      (10 microg/rat) increased memory retention by itself, and decreased the response
      induced by baclofen or imipramine. Bicuculline (1, 2 and 4 microg/rat, i.c.v.)
      tends to increase memory retention by itself. Furthermore, bicuculline in same
      doses reduced the response induced by muscimol or imipramine, but it did not show
      interaction with the latter drugs. It is concluded that the GABA(B) receptor
      mechanism is involved in memory impairment induced by imipramine.

PMID- 14659989
TI  - Both low and high activities of platelet monoamine oxidase increase the
      probability of becoming a smoker.
AB  - Platelet monoamine oxidase (MAO) activity is a marker of personality and
      psychiatric vulnerability, but the direct inhibitory action of tobacco
      constituents on the enzyme distorts the association. In the present
      investigation, data from a prospective longitudinal study of smoking behaviour
      and platelet MAO activity in adolescents at ages 15 and 18 years were
      sequentially analysed using a second-order multiple logistic regression analysis.
      The odds of regular smoking at 18 years increased significantly with increasing
      absolute deviation of platelet MAO activity at 15 years from the mean. That is,
      both low and high platelet MAO activity at 15 years predicted a higher
      probability of becoming a smoker. These data suggest that smoking is associated
      with low platelet MAO activity not only because of the direct inhibitory effect
      of tobacco constituents on the enzyme, but also because subjects with low
      platelet MAO activity are more likely to become smokers. Furthermore, the
      possible association between above-average platelet MAO activity and behavioural
      phenotypes should be reexamined.

PMID- 14659990
TI  - Potentiation of imipramine-induced antinociception by nicotine in the formalin
      test.
AB  - In this study, the effect of cholinergic agents on imipramine antinociception in
      mice, in the formalin test, has been investigated. Intraperitoneal (i.p.)
      administration of different doses of imipramine (2.5, 5, 10, 20 and 30 mg/kg) or
      nicotine (0.25, 0.5, 0.75 and 1 mg/kg) induced a dose dependent antinociception
      in both the first and second phases of the formalin test in mice. The combination
      of imipramine with doses of 0.5 and 0.75 mg/kg of nicotine showed a potentiated
      response, in both phases of the test. However, neither hexamethonium (5 and 10
      mg/kg), atropine (0.25 mg/kg) or mecamylamine (0.25 mg/kg) altered the
      antinociception induced by imipramine. It is concluded that nicotinic receptor
      activation but not the cholinergic muscarinic mechanism is involved in the
      imipramine-induced antinociception.

PMID- 14659991
TI  - Influence of sexual hormone antagonists on the anticonvulsant action of
      conventional antiepileptic drugs against electrically- and pentylenetetrazol
      induced seizures in mice.
AB  - The present results refer to the action of three gonadal steroid antihormones,
      tamoxifen (TXF, an estrogen antagonist), cyproterone acetate (CYP, an
      antiandrogen) and mifepristone (MIF, a progesterone antagonist) on seizure
      phenomena in mice. TXF and CYP at their lowest protective dose in the
      electroconvulsive threshold test, enhanced the antiseizure efficacy of some
      antiepileptic drugs. TXF (20 mg/kg) potentiated the protective activity of
      valproate, diphenylhydantoin and clonazepam, but not that of carbamazepine or
      phenobarbital, against maximal electroshock-induced convulsions in female mice.
      CYP (40 mg/kg) enhanced the anticonvulsant action of valproate, carbamazepine,
      diphenylhydantoin and clonazepam, but not that of phenobarbital, against maximal
      electroshock in male animals. MIF failed to affect the electroconvulsive
      threshold or the efficacy of antiepileptic drugs in maximal electroshock. The
      effect of TXF or CYP upon the electroconvulsive threshold and on the action of
      antiepileptics was not reversed by sex steroid hormones (estradiol, testosterone,
      progesterone). However, the TXF-induced elevation of the electroconvulsive
      threshold was abolished by bicuculline, N-methyl-D-aspartic acid and kainic acid,
      and partially reversed by aminophylline, strychnine being ineffective in this
      respect. The action of CYP on the threshold for electroconvulsions was partially
      reversed by bicuculline and aminophylline. Both glutamatergic agonists and
      strychnine remained ineffective in this respect. Moreover, the action of TXF or
      CYP on the activity of antiepileptics was not influenced by strychnine, and
      reversed to various extents by the remaining convulsants. In contrast to maximal
      electroshock, none of the three antihormones affected the protective action of
      antiepileptic drugs against pentylenetetrazol-induced seizures in mice. Neither
      TXF nor CYP altered the free plasma levels of antiepileptic drugs, so a
      pharmacokinetic interaction is not probable. The combined treatment of the two
      antihormones with antiepileptic drugs, providing 50% protection against maximal
      electroshock, did not affect motor performance in mice, and did not result in
      significant long-term memory deficits. Our data indicate that steroid receptor
      mediated events may be indirectly associated with seizure phenomena in the
      central nervous system and can modulate the protective activity of some
      conventional antiepileptic drugs.

PMID- 14659992
TI  - Serotonin and its transporter on proliferation of fetal heart cells.
AB  - Besides neuronal transmission, serotonin (5-HT) also acts as a trophic signal
      during the development of the central nervous and neural crest systems. In this
      study, we report that in addition to trophic effect, 5-HT increases the
      proliferation of fetal heart cells. We showed for the first time that the
      cultured heart cells, express serotonin transporter (5-HTT), which confirmed the
      previously observed accumulation of 5-HT in developing heart. The influence of 5
      HT on developing heart cells is studied throughout the dosage. We found that 5-HT
      concentration at physiological level, 4 microM, permits an optimal proliferation
      of heart cells as indicated by the number of 5-bromo-deoxyuridine immunoreactive
      (BrdU-im) cells and myosin heavy chain immunoreactive cells (MF20-im);
      fluctuation towards either concentrations reduce the proliferation. We
      hypothesized that 5-HTT plays a role in the heart development. Our study
      indicated that the blockade of 5-HT uptake by paroxetine decreased the number of
      BrdU-im cells and MF20-im cells. These data indicate a role of 5-HT and 5-HTT on
      heart development. Abnormal 5-HT level or misuse of 5-HT uptake blocker may alter
      the heart development.

PMID- 14659993
TI  - Ecto-nucleotidase activities in spinal cord of rats changes as function of age.
AB  - An increase in ADP hydrolysis was observed in spinal cord synaptosomal fractions
      of 2-month-old Wistar male rats, when compared to other ages (1, 4 and 6 months
      of age), while no change in ATPase activity was observed. Conversely, in female
      rats, whilst no change in ADPase activity was observed in the spinal cord
      synaptosomal fraction, ATPase activity diminished with age, in 1-6-month-old
      animals. 5'-Nucleotidase activity was higher in the 4-month-old male and female
      rats in relation to 1 and 2-month-old animals. In the female rats, this activity
      continued to increase at least until 6 months of age. In conclusion, adenine
      nucleotides hydrolysis in synaptosomes from rat spinal cord is influenced by age
      and by gender. Since both ATP and adenosine may act as neuromodulators in the
      spinal cord, influencing several processes such as nociception, the regulation of
      ATP-metabolizing enzymes in spinal cord is probably important for the normal
      function of this tissue at different ages.

PMID- 14659995
TI  - Morphological development of microglia in the postnatal rat brain. A quantitative
      study.
AB  - Morphological transformation of lectin-positive microglia/macrophages in the
      developing rat cerebral hemisphere was analysed using quantitative methods.
      During the first postnatal month, the cells showed increases in their size and
      fractal dimension accompanied by a simultaneous decrease in their solidity.
      Regional variations in dynamics of the process indicated the existence of spatio
      temporal developmental gradients within the cerebral hemisphere wall which might
      correspond with regional patterns of neuronal differentiation. Results of the
      present study prove that the quantitative methods can be the source of reliable
      data replacing subjective cell typologies.

PMID- 14659994
TI  - Microglial activation state and lysophospholipid acid receptor expression.
AB  - We used a simple commercial magnetic immunobead method for the preparation of
      acutely isolated microglial cells from postnatal days 1-3 rat brain. With the
      exception of a 15 min enzyme incubation, all stages are carried out at 4 degrees
      C, minimizing the opportunity for changes in gene expression during the isolation
      to be reflected in changes in accumulated mRNA. The composition of the isolated
      cells was compared with that of microglial cultures prepared by conventional
      tissue culture methods, and the purity of microglia was comparable between the
      two preparations. RT-PCR analysis of several genes related to inflammatory
      products indicated that the acutely prepared cells were in a less activated
      condition than the conventionally tissue cultured cells. We examined the pattern
      of expression of receptors for lysophosphatidic acid (lpa) and sphingosine-1
      phosphate (S1P) using quantitative real-time PCR (TaqMan PCR) techniques. mRNA
      for LPA1, S1P1, S1P2, S1P3 and S1P5 was detected in these preparations, but the
      levels of the different receptor mRNAs varied according to the state of
      activation of the cells. mRNA for LPA3 was only detected significantly in
      cultured cell after lipopolysaccharide (LPS) stimulation, being almost absent in
      cultured microglia and undetectable in the acutely isolated preparations. The
      levels of mRNA of LPA1 and S1P receptors was reduced by overnight exposure to
      S1P, while the same treatment significantly up-regulated the level of LPA3 mRNA.

PMID- 14659996
TI  - Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz
      syndrome: implications for autism.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is a malformation/mental retardation
      syndrome resulting from an inborn error in 3beta-hydroxysteroid Delta7-reductase
      (DHCR7), the terminal enzyme required for cholesterol biosynthesis. Using a
      targeting strategy designed to virtually eliminate Dhcr7 activity, we have
      created a SLOS mouse model that exhibits commissural deficiencies, hippocampal
      abnormalities, and hypermorphic development of serotonin (5-HT) neurons. The
      latter is of particular interest with respect to current evidence that serotonin
      plays a significant role in autism spectrum disorders and the recent clinical
      observation that 50% of SLOS patients present with autistic behavior.
      Immunohistochemical analyses have revealed a 306% increase in the area of 5-HT
      immunoreactivity (5-HT IR) in the hindbrains of mutant (Dhcr7-/-) mice as
      compared to age-matched wild type animals. Amount of 5-HT IR was measured as
      total area of IR per histological section. Additionally, a regional increase as
      high as 15-fold was observed for the most lateral sagittal hindbrain sections. In
      Dhcr7-/- mice, an expansion of 5-HT IR into the ventricular zone and floor plate
      region was observed. In addition, the rostral and caudal raphe groups exhibited a
      radial expansion in Dhcr7-/- mice, with 5-HT IR cells present in locations not
      seen in wild type mice. This increase in 5-HT IR appears to represent an increase
      in total number of 5-HT neurons and fibers. These observations may help explain
      the behavioral phenotype seen in SLOS, and provide clues for future therapeutic
      interventions that utilize pharmacological modulation of the serotonergic system.

PMID- 14659997
TI  - Growth-related changes in cell body size and succinate dehydrogenase activity of
      spinal motoneurons innervating the rat soleus muscle.
AB  - Cell body sizes and oxidative enzyme (succinate dehydrogenase) activities of
      spinal motoneurons innervating the soleus muscle were determined in rats ranging
      in postnatal age from 3 to 13 weeks. The soleus motoneurons were labeled by a
      retrograde neuronal tracer, nuclear yellow. The mean cell body sizes of
      motoneurons increased from 3 to 7 weeks of age, while the mean succinate
      dehydrogenase activities of motoneurons decreased from 3 to 7 weeks of age. There
      were no changes in mean cell body size or mean succinate dehydrogenase activity
      of motoneurons from 7 to 13 weeks of age. An inverse relationship between cell
      body size and succinate dehydrogenase activity of motoneurons was observed,
      irrespective of age. These results indicate that motoneurons innervating the rat
      soleus muscle show the adult pattern of cell body size and succinate
      dehydrogenase activity at an earlier stage of postnatal growth, 7 weeks of age.

PMID- 14659998
TI  - Modulation of intracellular Cl- homeostasis by lectin-stimulation in Jurkat T
      lymphocytes.
AB  - We investigated changes in intracellular Cl(-) concentration ([Cl(-)](i)) during
      lectin-induced activation and proliferation in human Jurkat T lymphocytes. [Cl(
      )](i) was measured using Cl(-) fluorescence dye (N-(6-methoyquinolyl) acetoxy
      acetyl-ester, MQAE) methods. Lectins, phytohemagglutinin and concanavalin A, dose
      dependently increased [Cl(-)](i) and triggered intracellular Cl(-) oscillation in
      human Jurkat T lymphocytes. However, some mitochondria metabolism inhibitors,
      such as m-chlorocarbonylcyanide phenylhydrazone (CCP) and 2,4-dinitrophenol,
      increased [Cl(-)](i) without triggering any Cl(-) oscillation. Furthermore, both
      lectins and metabolism inhibitors-induced elevation in [Cl(-)](i) were blocked by
      removal of extracellular Cl(-) from perfusion solution or by application of
      anthracene-9-carboxylate, a blocker of Cl(-) channels. Since an extracellular Cl(
      )-free condition and application of 9-AC also inhibited PHA-induced
      proliferation, we suggested that elevation of [Cl(-)](i) via activation of Cl(-)
      channels and increase in incidence of Cl(-) oscillation would play an important
      role in modulation of Jurkat T cell activation and proliferation.

PMID- 14659999
TI  - Transporter-mediated actions of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane.
AB  - R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] is a catecholaminergic
      and serotonergic activity enhancer that increases impulse-evoked catecholamine
      and serotonin release from nerve terminals, and is a candidate for symptomatic
      treatment of early Parkinson's disease. We now report the catecholamine and
      serotonin transporter-mediated actions of (-)-BPAP. The effects of (-)-BPAP on
      inhibition of neurotransmitter uptake and radioligand binding were assessed using
      human embryonic kidney 293 cells (HEK 293 cells) expressing cDNA for the human
      dopamine transporter (hDAT), norepinephrine transporter (hNET), and serotonin
      transporter (hSERT). The IC(50) values for the effects of (-)-BPAP on
      [3H]dopamine, [3H]norepinephrine, and [3H]serotonin uptake were 42+/-9, 52+/-19,
      and 640+/-120 nM, respectively. The IC(50) values for the effects of (-)-BPAP on
      [125I]3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester ([125I]RTI
      55) binding to hDAT, hNET, and hSERT were 16+/-2, 211+/-61, and 638+/-63 nM,
      respectively. The effects of (-)-BPAP on spontaneous and tyramine-induced
      norepinephrine and dopamine release from rat brain synaptosomes using a
      superfusion system were also assessed. Tyramine but not (-)-BPAP potentiated
      norepinephrine release. Furthermore, (-)-BPAP inhibited tyramine-induced
      norepinephrine release. Thus, (-)-BPAP may block tyramine-induced adverse effects
      such as hypertensive crisis. The actions of (-)-BPAP on the spontaneous and
      tyramine-induced dopamine release resembled its effects on norepinephrine
      release. We conclude that (-)-BPAP is not only catecholaminergic and serotonergic
      activity enhancer, but also a norepinephrine and dopamine uptake inhibitor and a
      weak serotonin uptake inhibitor that does not possess a tyramine-like action on
      catecholamine release, and is an inhibitor of tyramine-induced release of
      norepinephrine.

PMID- 14660000
TI  - Expression of OP4 (ORL1, NOP1) receptors in vascular endothelium.
AB  - Endothelial cells from rat brain microvessels, human aortic artery and human
      umbilical vein were examined, together with ex vivo rat brain capillaries and rat
      aortic ring sections, for the expression of opioid receptor-like OP-4 mRNA and
      protein. High levels of mRNA expression and an immunopositive reaction for the
      receptor protein were detected in the endothelial cells from primary and from
      established in vitro cultures, as well as in the intima of ex vivo rat aortic
      rings, where the signal was limited to the endothelial layer. Interaction of the
      OP4 receptor with its physiological ligand nociceptin caused, in cultured
      endothelial cells, the activation of a mitogen-activated protein (MAP) kinase
      cascade. Taken together, these results show that the OP4 receptor is synthesised
      and functionally expressed in endothelial cells, presumably as a starting point
      for some vasoactive mechanism(s).

PMID- 14660001
TI  - Functional role of nicotinic acetylcholine receptors in apoptosis in HL-60 cell
      line.
AB  - The subunit composition of nicotinic acetylcholine receptors involved in
      apoptosis is an ongoing question. HL-60 cells were used in order to investigate
      the implication of nicotinic acetylcholine receptors in bleomycin-induced
      apoptosis. We found that bleomycin-induced apoptosis was significantly enhanced
      by nicotine and was blocked by nicotinic acetylcholine receptor antagonists,
      including alpha-bungarotoxin, a competitive antagonist of alpha 7 nicotinic
      receptor. Among the other agonists tested, 3-[2,4-dimethoxybenzylidene]anabaseine
      (GTS-21)-selective agonist for alpha 7-nicotinic acetylcholine receptor-, but not
      epibatidine or cytisine, enhanced bleomycin-induced apoptosis. In addition to
      these results, the detectable presence of alpha 7-mRNA supports a key role of
      alpha 7-nicotinic acetylcholine receptors in the modulation of the induced
      apoptosis by nicotine.

PMID- 14660002
TI  - Dopamine receptor agonists differ in their actions on cardiac ion channels.
AB  - Four dopamine receptor agonists used for the treatment of Parkinson's disease
      (apomorphine, pergolide, ropinirole and sumanirole) were evaluated for the
      ability to block human ether-a-go-go related gene (hERG) K(+) channels and to
      modify the duration of canine Purkinje fiber action potentials. Apomorphine,
      pergolide and ropinirole blocked the hERG-mediated currents with IC(50) values of
      2.4, 0.12 and 1.2 microM, respectively. When evaluated in an action potential
      duration assay, pergolide significantly shortened action potential duration at
      90% repolarization (APD(90)) whereas apomorphine and ropinirole significantly
      prolonged repolarization. Sumanirole only partially blocked hERG K(+) channels at
      the highest tested concentration (10 microM) and did not modify action potential
      duration over the tested concentration range (0.65-65 microM). Taken together,
      these data provide evidence that dopamine receptor agonists developed for the
      treatment of Parkinson's disease differentially influence hERG K(+) channel
      function and cardiac action potential duration.

PMID- 14660003
TI  - Role of mitogen-activated protein kinases in endothelin ETB receptor up
      regulation after organ culture of rat mesenteric artery.
AB  - Organ culture of isolated arteries results in increased levels of endothelin
      ET(B) (ET(B)) receptor mRNA and in enhanced ET(B) receptor mediated contraction.
      The present study was designed to pinpoint the mitogen-activated protein kinase
      (MAPK) subtype involved in up-regulation of ET(B) receptors after organ culture
      of rat mesenteric arteries. Western blot and selective antibodies towards
      constitutional and phosphorylated MAPKs revealed the appearance of phosphorylated
      MAPK of the extracellular signal-regulated kinases (ERK) 1/2 type at 3 h of organ
      culture. The functional ET(B) receptor and its mRNA expression were up-regulated
      after 24 h of organ culture. Following incubation with the MEK 1/2 specific
      inhibitor SB408039 or the raf inhibitor SB386023b the up-regulation was
      attenuated both for ET(B) receptor responses and in ET(B) receptor mRNA
      expression in the vessel segments. Neither Western blot nor myograph or mRNA
      analysis showed involvement of the other MAPKs studied. Our results suggest that
      the ERK1/2 MAPKs are involved in the endothelin ET(B) receptor up-regulation
      following organ culture.

PMID- 14660004
TI  - Cloning and pharmacological characterization of the monkey histamine H3 receptor.
AB  - Species differences have been described previously for histamine H(3) receptor
      pharmacology. Rat selective histamine H(3) receptor ligands such as ciproxifan
      and A-304121 (2-amino-1-[4-[3-(4-cyclopropanecarbonyl-phenoxy)-propyl]-piperazin
      1-yl]-propan-1-one) show over 100-fold selectivity for the rat receptor compared
      to the human receptor. To date, however, the pharmacology of the cloned monkey
      histamine H(3) receptor has not been examined. In this study, we cloned the
      monkey histamine H(3) receptor gene (H(3)R) and evaluated the receptor
      pharmacology in binding and functional assays. The monkey histamine H(3) receptor
      is highly homologous to the human receptor with 438 identities in their 445 amino
      acid sequences, but less homologous to the rat receptor. However, unlike the
      human or rat, we found no evidence for additional splicing for the monkey H(3)R.
      Pharmacological analysis indicated that the monkey receptor exhibited similar
      pharmacological profiles to those of the human receptor, providing critical
      information for characterizing histamine H(3) receptor ligands in monkey
      behavioral models.

PMID- 14660005
TI  - Cocaine induces apoptosis in cerebral vascular muscle cells: potential roles in
      strokes and brain damage.
AB  - Cocaine abuse is known to induce different types of brain-microvascular damage
      and many adverse cerebrovascular effects, including cerebral vasculitis,
      intracranial hemorrhage, cerebral infarction and stroke. A major physiological
      event leading to these pathophysiological actions of cocaine could be apoptosis.
      Whether cocaine can cause brain-microvascular pathology and vascular toxicity by
      inducing apoptosis of cerebral vascular smooth muscle cells is not known. This
      study, using several different methods to discern apoptosis, was designed to
      investigate if primary cultured canine cerebral vascular smooth muscle cells can
      undergo apoptosis when treated with cocaine. After treatment with cocaine (10(-6)
      10(-3) M) for 12-24 h, the death rates of cerebral vascular smooth muscle cells
      increased in a concentration-dependent manner compared with controls.
      Morphological analysis of cerebral vascular smooth muscle cells using confocal
      fluoresence microscopy showed that the percentage of apoptotic cerebral vascular
      smooth muscle cells increased after cocaine (10(-6)-10(-3) M) treatment in a
      concentration-dependent manner. TUNEL assays also showed positive results for
      cerebral vascular smooth muscle cells treated with cocaine. These results clearly
      demonstrate that cerebral vascular smooth muscle cells can undergo rapid
      apoptosis in response to cocaine in a concentration-dependent manner. Cocaine
      induced apoptosis may thus play a major role in brain-microvascular damage,
      cerebral vascular toxicity and strokes.

PMID- 14660006
TI  - Differential involvement of protein kinase C in human promyelocytic leukemia cell
      differentiation enhanced by artemisinin.
AB  - Artemisinin, a sesquiterpene lactone endoperoxide that exists in several
      medicinal plants, is a well-known anti-malarial agent. In this report, we
      investigated the effect of artemisinin on cellular differentiation in the human
      promyelocytic leukemia HL-60 cell culture system. Artemisinin markedly increased
      the degree of HL-60 leukemia cell differentiation when simultaneously combined
      with low doses of 1 alpha,25-dihydoxyvitamin D(3) [1,25-(OH)(2)D(3)] or all-trans
      retinoic acid (all-trans RA). Artemisinin by itself had very weak effects on the
      differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic
      studies indicated that artemisinin potentiated 1,25-(OH)(2)D(3)-induced cell
      differentiation predominantly into monocytes and all-trans RA-induced cell
      differentiation into granulocytes, respectively. Extracellular-regulated kinase
      (ERK) inhibitors markedly inhibited HL-60 cell differentiation induced by
      artemisinin in combination with 1,25-(OH)(2)D(3) or all-trans RA, whereas
      phosphatidylinositol 3-kinase (PI3-K) inhibitors did not. Particularly, protein
      kinase C (PKC) inhibitors inhibited HL-60 cell differentiation induced by
      artemisinin in combination with 1,25-(OH)(2)D(3) but not with all-trans RA.
      Artemisinin enhanced PKC activity and protein level of PKC beta I isoform in only
      1,25-(OH)(2)D(3)-treated HL-60 cells. Taken together, these results indicate that
      artemisinin strongly enhanced 1,25-(OH)(2)D(3)- and all-trans RA-induced cell
      differentiation in which PKC is differentially involved in arteminisin-mediated
      enhancement of leukemia cell differentiation.

PMID- 14660007
TI  - Potent induction of apoptosis by germacranolide sesquiterpene lactones on human
      myeloid leukemia cells.
AB  - This paper studies the cytotoxic effect induced by four known natural
      sesquiterpene lactones (tatridin A, tamirin, reynosin, ineupatorolide A) and one
      synthetic derivative (tatridin A diacetate) on the myeloid leukemia cell lines HL
      60 and U937. Tatridin A diacetate and ineupatorolide A were found to be the most
      cytotoxic compounds with growth inhibition caused by induction of apoptosis as
      determined by flow cytometry and microscopy of nuclear changes. The results
      reported here support the conclusion that apoptosis was accompanied by both the
      activation of caspase-3 and the fragmentation of poly(ADP-ribose) polymerase-1
      and was also associated with an early release of cytochrome c from the
      mitochondria.

PMID- 14660008
TI  - Proopiomelanocortin and melanocortin receptors in the adult rat retino-tectal
      system and their regulation after optic nerve transection.
AB  - The aim of this study was to characterise the expression of the melanocortin
      system in the normal and injured rat visual system. Using real-time polymerase
      chain reaction and immunohistochemistry, we detected melanocortin MC(3), MC(4)
      and MC(5) receptors and proopiomelanocortin in adult retina and superior
      colliculus. Melanocortin MC(4) receptor mRNA was the most abundant receptor.
      Melanocortin MC(3), MC(4) and MC(5) receptors were localised to the ganglion cell
      and inner nuclear layers and the melanocortin MC(3) and MC(4) receptors were
      localised to retinal ganglion cells. Transection of the optic nerve leads to
      ganglion cell death and both melanocortin receptor and proopiomelanocortin
      expression decreased in superior colliculus after transection whereas the
      expression was unchanged or even increased in the retina. alpha-Melanocyte
      stimulating hormone elicited neurite outgrowth from embryonic retinal explants.
      Together, these data implicate a role for the melanocortin system in the adult
      rat retina and that melanocortins can stimulate neurite growth from retinal
      neurons.

PMID- 14660009
TI  - The effect of angiotensin-converting enzyme inhibition on endothelial function
      and oxidant stress.
AB  - Angiotensin-converting enzyme (ACE) inhibitors effectively interfere with the
      renin-angiotensin system and exert various beneficial actions on vascular
      structure and function beyond their blood pressure-lowering effects. Data from
      experimental studies showed that angiotensin-converting enzyme inhibitors can
      attenuate the development of atherosclerosis in a wide range of species. The
      postulated mechanisms of this atheroprotective effect are the antioxidant actions
      of angiotensin-converting enzyme inhibitors and their enhancement of the
      endothelial elaboration of bioactive nitric oxide. The aim of this study was to
      assess the comparative effects of three angiotensin-converting enzyme inhibitors
      on endothelial nitric oxide production and action, and on endothelial oxidative
      stress. Using bovine aortic endothelial cells in culture grown to confluence, we
      examined the effects of 1, 10, 30 and 60 microM of each of captopril, zofenopril
      and enalapril on nitrite/nitrate accumulation in the media, cyclic GMP
      accumulation in the cell lysate, and F(2)-isoprostanes in lipid extracts from the
      cells. Results showed that the sulfhydryl angiotensin-converting enzyme inhibitor
      zofenopril has unique properties compared with captopril and enalapril. This
      compound improves nitric oxide production and bioactivity, and does so in
      conjunction with decreased endothelial cell oxidant stress. The biochemical basis
      for this protective mechanism is not entirely clear; however, these actions
      suggest that zofenopril may reduce endothelial effects of risk factors for
      atherothrombotic disease.

PMID- 14660010
TI  - Muscarinic receptor subtypes in the human colon: lack of evidence for atypical
      subtypes.
AB  - Characteristics of muscarinic receptors were investigated in circular muscle from
      normal human colon. In saturation studies (n=18), binding of [3H]quinuclidinyl
      benzylate (QNB) was of high affinity (K(d) 87.3 pM) and capacity (B(max) 362+/-27
      fmol/mg protein), with no differences between ascending and sigmoid colon.
      Kinetic studies gave a K(d) of 55 pM. Methoctramine and darifenacin displayed
      biphasic binding profiles, the high affinity components being compatible with a
      population of approximately 80+/-5% M(2) and 13+/-2% M(3) muscarinic receptors,
      respectively. Pirenzepine, mamba toxin 1 and mamba toxin 3 were very weak
      competitors, indicating negligible expression of muscarinic M(1) and M(4)
      receptors. Six other subtype-preferring antagonists exhibited K(i) values typical
      of those reported at cloned human muscarinic M(2) receptors. In the presence of
      methoctramine, pre-treatment with alkylating agent 4-diphenylacetoxy-N-(2
      chloroethyl)-piperidine hydrochloride (4-DAMP mustard) inhibited
      [3H]quinuclidinyl benzylate binding to 26% of sites. Following alkylation of
      muscarinic M(3) receptors, darifenacin bound to a single low affinity site,
      indicating binding to muscarinic M(2) receptors.

PMID- 14660011
TI  - Characterization of specific delta-opioid binding sites in the distal small
      intestine of swine.
AB  - Delta-opioid receptors modulate neurogenic smooth muscle contractions and mucosal
      ion transport in the porcine distal small intestine. We compared specific delta
      opioid binding sites in neuronal membranes isolated from the inner submucosal
      plexus and myenteric plexus of this gut region. In both preparations, the delta
      opioid receptor antagonist naltrindole displaced [3H]diprenorphine from two
      binding sites. [3H]Naltrindole bound specifically to a single high-affinity site
      that was displaced by delta-opioid receptor ligands with the rank order of
      affinity: naltriben >7-benzylidenenaltrexone>deltorphin II>[D-Pen(2), D-Pen(5)]
      enkephalin. Relative decreases in delta-opioid receptor agonist affinity in the
      presence of Na(+) and other ions differed in submucosal and myenteric membranes.
      The kappa-opioid receptor antagonist norbinaltorphimine displaced [3H]naltrindole
      binding in myenteric membranes (K(i)=7.2 nM). Delta-opioid receptors in
      submucosal and myenteric plexuses of porcine ileum appear to differ in some
      respects.

PMID- 14660012
TI  - Prolonged exposure to gamma-aminobutyric acid up-regulates stably expressed
      recombinant alpha 1 beta 2 gamma 2s GABAA receptors.
AB  - The aim of this study was to better understand the mechanisms that underlie
      adaptive changes in GABA(A) receptors following their prolonged exposure to
      drugs. Exposure (48 and/or 96 h) of human embryonic kidney (HEK 293) cells stably
      expressing recombinant alpha1beta2gamma2s GABA(A) receptors for gamma
      aminobutyric (GABA, 1 mM) and muscimol (100 microM), but not for diazepam (1
      microM), enhanced the maximum number (B(max)) of [3H]flunitrazepam binding sites
      without affecting their affinity (K(d)). The GABA-induced enhancement in B(max)
      was reduced by the GABA receptor antagonist, bicuculline (100 microM), and by
      cycloheximide (10 microl/ml), a protein synthesis inhibitor. GABA (100 microM)
      enhanced the affinity of [3H]flunitrazepam binding to vehicle- and GABA
      pretreated, but not to diazepam-pretreated, HEK 293 cells. The results suggest
      that chronic GABA treatment up-regulates stably expressed GABA(A) receptors,
      presumably by stimulating their synthesis. Unlike chronic diazepam, which
      produced functional uncoupling of GABA and benzodiazepine binding sites, chronic
      GABA failed to produce this effect.

PMID- 14660013
TI  - Melanocortin receptor agonists and antagonists modulate nociceptive sensitivity
      in the mouse formalin test.
AB  - A number of studies suggest the involvement of melanocortins in nociception, and
      although the mechanism through which this occurs is still unknown, experimental
      evidence would suggest an involvement of melanocortin MC(4) receptors. We
      investigated the effect of melanocortin receptor agonist and antagonists on
      nociceptive behaviour induced by formalin in the mouse. The intrathecal injection
      of the melanocortin receptor agonist MTII ([Ac-Nle(4),Asp(5),D
      Phe(7),Lys(10)]cyclo-alpha-MSH-(4-10) amide) (5 nmol; P<0.05) significantly
      increased nociception in both phases of the formalin test, whereas the synthetic
      melanocortin receptor antagonists, SHU9119 ([Ac-Nle(4),Asp(5),D-2
      Nal(7),Lys(10)]cyclo-alpha-MSH-(4-10) amide) (5 nmol), HS014 ([Ac-Cys(11),D-2
      Nal(14),Cys(18)]beta-MSH-(11-22)amide) (5 nmol), and JKC-363 (cyclic [Mpr(11),D
      Nal(14),Cys(18),Asp(22)-NH(2)]beta-MSH-11-22)) (5 nmol), and the endogenous
      receptor antagonist Agouti-related protein (AgRP) (1.5 nmol) were effective in
      reducing nociception in the late phase of the formalin test (50-60% of reduction
      in licking/flinching response; P<0.05). The present findings further support the
      involvement of the melanocortin system in the control of nociception. Moreover,
      considering that melanocortin MC(4) receptors are the only melanocortin subtype
      receptors present in the spinal cord, we can assume that the activity of the
      peptides in the formalin model is mediated through melanocortin MC(4) receptors.

PMID- 14660014
TI  - Systemic galnon, a low-molecular weight galanin receptor agonist, reduces heat
      hyperalgesia in rats with nerve injury.
AB  - We have examined the effect of systemically administered galnon, a novel low
      molecular weight agonist of galanin receptors, on neuropathic pain-like behaviors
      in rats after photochemically induced partial nerve injury. Galnon is a galanin
      receptor ligand with moderate affinity to spinal cord membranes (K(D) of 6+/-0.6
      microM). While intraperitoneally applied galnon produced no significant effect on
      mechanical or cold hypersensitivity, it dose-dependently prolonged heat
      withdrawal latency in nerve-injured rats. The effect of galnon was more potent on
      the injured side which has significantly shorter latency than the contralateral
      side. The anti-hyperalgesic effect of galanon was prevented by intrathecal M35, a
      galanin receptor antagonist. No side effects, such as sedation or motor
      impairment, were seen following systemic galnon treatment at the doses used. It
      is concluded that systemic galnon alleviated heat-hyperalgesic response in rats
      with partial sciatic nerve injury. This effect was likely to be mediated by
      activation of spinal galanin receptors.

PMID- 14660015
TI  - Na+-dependent high affinity binding of [3H]LY515300, a 3,4-dimethyl-4-(3
      hydroxyphenyl)piperidine opioid receptor inverse agonist.
AB  - Analogues of 3,4-dimethyl-4-(3-hydroxyphenyl)piperidines are high affinity
      inverse agonists for micro-, delta- and kappa-opioid receptors. To characterize
      inverse agonist binding, we synthesized a high specific activity radioligand from
      this series, [3H]LY515300 (3-[1-((3-cyclohexyl-[3,4-3H(2)])-3(R,S)-hydroxypropyl)
      3(R),4(R)-dimethylpiperidin-4-yl]phenol). In membranes expressing cloned human
      opioid receptors, [3H]LY515300 binding was saturable and exhibited low
      nonspecific binding. [3H]LY515300 bound with high affinity to the micro-
      (K(d)=0.07 nM), delta- (K(d)=0.92 nM) and kappa-(K(d)=0.45 nM) opioid receptors.
      High affinity [3H]LY515300 binding to all opioid receptors was Na(+)-dependent, a
      characteristic of inverse agonists. Displacement by standard opioid compounds
      yielded K(i) values consistent with their known opioid receptor affinities.
      Autoradiographic localization of specific [3H]LY515300 binding in rat and guinea
      pig brain was high in areas known to express high levels of opioid (particularly
      micro-opioid receptor) binding sites including the caudate, nucleus accumbens,
      and nucleus tractus solitarius. Thus, [3H]LY515300 is the first radiolabeled
      opioid receptor inverse agonist useful for the study of opioid receptors in cell
      lines and native tissues.

PMID- 14660016
TI  - The role of hyperthermia and metabolism as mechanisms of tolerance to
      methamphetamine neurotoxicity.
AB  - Pretreatment with multiple methamphetamine injections prior to a high-dose
      methamphetamine challenge administration can attenuate long-term deficits in
      striatal and hippocampal serotonin content caused by the stimulant. The present
      data extend previous findings by demonstrating that rats pretreated with
      escalating doses methamphetamine did not exhibit dopamine deficits in the
      striatum, nor serotonin deficits in striatal, frontal cortical, or hippocampal
      tissues, 7 days after a challenge methamphetamine administration. This protection
      was not due to attenuation of methamphetamine-induced hyperthermia or altered
      brain methamphetamine concentrations. These data differ from previous findings
      thereby highlighting that different mechanisms contribute to the tolerance of the
      neurotoxic effects.

PMID- 14660017
TI  - Serotonergic depression of spinal monosynaptic transmission is mediated by 5-HT1B
      receptors.
AB  - In the spinal cord, various subtypes of serotonin (5-hydroxytryptamine; 5-HT)
      receptors are involved in the modulation of motor output. Although the excitatory
      role of 5-HT(2) receptors is known, the receptor subtypes mediating the
      inhibitory effect of 5-HT on monosynaptic reflex transmission remain unclear. In
      this study, segmental spinal reflexes were recorded to examine the receptor
      subtypes underlying 5-HT-mediated inhibition of monosynaptic reflex transmission
      in spinalized rats. Under conditions of monoamine oxidase blockade with
      clorgyline, the 5-HT precursor L-5-hydroxytryptophan depressed the monosynaptic
      reflex. 3-Hydroxybenzylhydrazine dihydrochloride (NSD-1015), a centrally active
      decarboxylase inhibitor, abolished this inhibition, confirming that the
      depression of the monosynaptic reflex by L-5-hydroxytryptophan was due to 5-HT.
      In the presence of GR127935 or isamoltane, which show high affinity for 5-HT(1B)
      receptors, L-5-hydroxytryptophan did not suppress the monosynaptic reflex,
      whereas 5-HT(1A), 5-HT(1D), 5-HT(2) and 5-HT(7) receptor antagonists did not
      alter the inhibitory effect of L-5-hydroxytryptophan. These results suggest that
      serotonergic depression of monosynaptic reflex transmission is mediated by 5
      HT(1B) receptors.

PMID- 14660018
TI  - Relationship between plasma and brain levels and the anticonvulsant effect of
      lamotrigine in rats.
AB  - The aims of the present research were to characterize the plasma and brain
      concentration-time profiles of lamotrigine after its acute administration and to
      establish the relationship between these profiles and the anticonvulsant effect
      of lamotrigine in rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine
      intraperitoneally. The lamotrigine profiles in plasma and brain were determined
      at predetermined times over 120-h post-dose. The anticonvulsant profile against
      maximal electroshock seizure stimulation was determined over 48 h after dosing.
      After injection, lamotrigine rapidly appeared in both plasma and brain,
      suggesting ready penetration of the blood-brain barrier. A linear relationship
      was established between lamotrigine plasma and brain levels. A linear
      relationship was also defined between lamotrigine brain levels and the
      anticonvulsant response. The correspondent plasma levels were also well
      correlated with the anticonvulsant effect from the moment that the plasma-brain
      system had reached equilibrium.

PMID- 14660019
TI  - Effects of clobenpropit on pentylenetetrazole-kindled seizures in rats.
AB  - The purpose of this study was to investigate whether or not clobenpropit, a
      selective and potent histamine H(3) receptor antagonist, can protect from
      pentylenetetrazole (35 mg/kg)-kindled seizures in rats. I.c.v. injection with
      clobenpropit (10 and 20 microg) significantly delayed the seizure stage and
      prolonged the latency to the onset of myoclonic jerks and the latency to the
      clonic generalized seizure in a dose-dependent manner. The protection by
      clobenpropit (20 microg) was completely antagonized by both immepip (5 and 10
      microg, i.c.v.), a selective potent histamine H(3) receptor agonist, and alpha
      fluoromethylhistidine (alpha-FMH, 50 microg, i.c.v.), a selective histidine
      decarboxylase inhibitor. In addition, clobenpropit markedly potentiated the
      histidine (100 and 200 mg/kg)-induced inhibition of pentylenetetrazole-kindled
      seizures. Pyrilamine (2 and 5 microg, i.c.v.) reversed the inhibition of
      pentylenetetrazole-kindled seizures induced by clobenpropit, whereas cimetidine
      had no effect even at a high dose of 5 microg. These results indicate that
      clobenpropit protects against pentylenetetrazole-kindled seizures in rats, and
      that its action is mainly due to the activation of endogenous histamine by
      blocking autoinhibitory presynaptic histamine H(3) receptors.

PMID- 14660020
TI  - Involvement of GABAA receptors in the regulation of the prefrontal cortex on
      dopamine release in the rat dorsolateral striatum.
AB  - The characteristics of the prefrontal cortex regulation of dopamine release in
      the rat dorsolateral striatum were investigated in focusing on the
      corticostriatal pathway, using dual-probe microdialysis in combination with
      simple behavioral procedures. Intracortical perfusion of the GABA(A) receptor
      antagonist bicuculline (0.03 and 0.1 mM) increased the striatal dopamine release,
      whereas the GABA(A) receptor agonist muscimol (0.1 and 1 mM) reduced the release
      dose dependently. Co-perfusion of muscimol (0.01 mM), which did not by itself
      affect the dopamine release, completely prevented the glutamate (1 mM)-stimulated
      dopamine release and behavioral activities, including locomotion and rearing.
      Muscimol (0.01 mM) also prevented the N-methyl-D-aspartate (NMDA; 1 mM)-induced
      increases in glutamate, as well as dopamine levels. These findings suggest that
      the prefrontal cortex functionally regulates dopamine release in the dorsolateral
      striatum, which is mediated via GABA(A) receptors. This cortical GABAergic system
      underlying the prefrontal cortex regulatory mechanism appears to be associated
      with the corticostriatal pathway.

PMID- 14660021
TI  - Basal and feeding-evoked dopamine release in the rat nucleus accumbens is
      depressed by leptin.
AB  - The involvement of the satiety-controlling hormone leptin in the modulation of
      the reward-associated dopamine release was investigated by monitoring the
      extracellular dopamine concentration in microdialysates from the nucleus
      accumbens of rats during feeding after infusion of leptin or artificial
      cerebrospinal fluid into the lateral ventricle of rats. Leptin suppressed the
      basal as well as the feeding-evoked extracellular dopamine concentration and
      reduced the amount and duration of food intake compared to the pair-feed vehicle
      treated controls. These results suggest that leptin is involved in the
      dopaminergic modulation of feeding-induced rewarding functions.

PMID- 14660022
TI  - Effects of the beta-carbolines, harmane and pinoline, on insulin secretion from
      isolated human islets of Langerhans.
AB  - It is well known that certain imidazoline compounds can stimulate insulin
      secretion and this has been attributed to the activation of imidazoline I(3)
      binding sites in the pancreatic beta-cell. Recently, it has been proposed that
      beta-carbolines may be endogenous ligands having activity at imidazoline sites
      and we have, therefore, studied the effects of beta-carbolines on insulin
      secretion. The beta-carbolines harmane, norharmane and pinoline increased insulin
      secretion two- to threefold from isolated human islets of Langerhans. The effects
      of harmane and pinoline were dose-dependent (EC(50): 5 and 25 microM,
      respectively) and these agents also blocked the inhibitory effects of the
      potassium channel agonist, diazoxide, on glucose-induced insulin release.
      Stimulation of insulin secretion by harmane was glucose-dependent but, unlike the
      imidazoline I(3) receptor agonist efaroxan, it increased the rate of insulin
      release beyond that elicited by 20 mM glucose (20 mM glucose alone: 253+/-34% vs.
      basal; 20 mM glucose plus 100 microM harmane: 327+/-15%; P<0.01). Stimulation of
      insulin secretion by harmane was attenuated by the imidazoline I(3) receptor
      antagonist KU14R (2 (2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole) and was
      reduced when islets were treated with efaroxan for 18 h, prior to the addition of
      harmane. The results reveal that beta-carbolines can potentiate the rate of
      insulin secretion from human islets and suggest that these agents may be useful
      prototypes for the development of novel insulin secretagogues.

PMID- 14660023
TI  - Anxiolytic-like effects of the selective 5-HT1A receptor antagonist WAY 100635 in
      non-human primates.
AB  - Non-human primates provide important insights into the potential use of 5-HT(1A)
      receptor antagonists in treating human anxiety disorders and as research tools,
      given the existent inconsistencies in rodent tests. This study investigated the
      effects of the selective silent 5-HT(1A) receptor antagonist N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide
      trihydrochloride (WAY 100635), administered systemically, in an ethologically
      based fear/anxiety test in marmoset monkeys (Callithrix penicillata). Subjects
      were tested using a figure-eight maze and a taxidermized wild cat as 'predator'
      stimulus. After seven 30-min maze habituations in the absence of the 'predator',
      each animal was submitted to four pseudo-randomly assigned 30-min treatment
      trials in the presence of the 'predator': three WAY 100635 (0.2, 0.4 and 0.8
      mg/kg, i.p.) sessions and a saline control trial. The 'predator' stimulus caused
      a significant fear-induced avoidance of the maze sections closest to where it was
      presented, indicating an anxiogenic effect. However, WAY 100635 treatment
      reversed, significantly and dose-dependently, this fear-induced avoidance
      behavior, while increasing maze exploration. Sedation was not observed. This is
      the first study to suggest an anxiolytic-like effect of the selective silent 5
      HT(1A) receptor antagonist WAY 100635 in non-human primates, indicating its
      potential use as a therapeutic agent.

PMID- 14660024
TI  - Role of nitric oxide in the acquisition and expression of apomorphine- or
      morphine-induced locomotor sensitization.
AB  - In the present study, the effects of L-arginine, a nitric oxide (NO) precursor,
      and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS)
      inhibitor, on apomorphine- or morphine-induced locomotor sensitization in male
      albino mice were investigated. Our data showed that subcutaneous (s.c.) injection
      of apomorphine (2-10 mg/kg) or morphine sulphate (5-50 mg/kg) significantly
      increased locomotor behaviour in a dose-dependent manner. Intraperitoneal (i.p.)
      administration of L-arginine (100 mg/kg) increased locomotor activity, whereas L
      NAME (20 mg/kg) decreased it. L-Arginine and L-NAME increased and decreased
      apomorphine- or morphine-induced locomotions, respectively. The locomotor
      behavioural response was enhanced in mice pretreated with apomorphine (2 mg/kg,
      daily x3 days) or morphine (10 mg/kg, daily x3 days) alone, indicating that
      sensitization had developed. Administration of L-arginine 30 min before each of
      three daily doses of apomorphine or morphine increased the development of
      sensitization, while administration of L-NAME 30 min before each of three daily
      doses of apomorphine or morphine decreased the acquisition of sensitization
      induced by apomorphine or morphine. Administration of L-arginine significantly
      increased and L-NAME significantly and dose-dependently decreased the expression
      of both apomorphine- and morphine-induced sensitization. The results indicate
      that NO may be involved in the acquisition and expression of apomorphine- or
      morphine-induced sensitization.

PMID- 14660025
TI  - Rotarod studies in the rat of the GABAA receptor agonist gaboxadol: lack of
      ethanol potentiation and benzodiazepine cross-tolerance.
AB  - All benzodiazepines and benzodiazepine site agonists impair motor performance
      dose-dependently and potentiate the effects of ethanol. In order to evaluate the
      risk of benzodiazepine and ethanol interaction with the direct acting GABA(A)
      receptor agonist 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol (gaboxadol), we
      studied impairment of motor coordination for combinations of gaboxadol, ethanol
      and a series of benzodiazepines (flunitrazepam, zolpidem and indiplon) in a rat
      rotarod model. All compounds produced a dose-dependent motor impairment and, in
      agreement with earlier data, a supra-additive effect of the benzodiazepine
      ligands and ethanol 1 g/kg was seen. In contrast, no significant potentiation of
      the effects of gaboxadol by ethanol was detected, and furthermore, no synergistic
      interaction between gaboxadol and any of the benzodiazepines was seen. A 30-day
      tolerance study was conducted with daily injections of gaboxadol (7.9 mg/kg) and
      zolpidem (1.25 mg/kg), respectively. A time-dependent tolerance developed to the
      motor impairment produced by both compounds. On day 31, cross-tolerance studies
      between zolpidem/gaboxadol and gaboxadol/zolpidem were conducted. No cross
      tolerance was observed, indicating that the motor coordination effects observed
      with gaboxadol and zolpidem may arise from interaction with different receptor
      populations.

PMID- 14660026
TI  - Non-steroidal anti-inflammatory drugs antagonise the constipating effects of
      tramadol.
AB  - We report an antagonistic interaction between tramadol and non-steroidal anti
      inflammatory drugs (NSAIDs), on gastrointestinal transit in rats. Transit was
      evaluated with charcoal and results are expressed as %inhibition. Tramadol and
      morphine had ED(50)s of 120.70+/-9.54 and 3.20+/-0.26 mg/kg, respectively, while
      metamizol (85 mg/kg), paracetamol (100 mg/kg) or ibuprofen (50 mg/kg) had no
      effect. All combinations of tramadol plus an NSAID, resulted in a rightward, non
      parallel shift of the curves, which showed (two-way analysis of variance, ANOVA)
      significant differences from tramadol alone for the dose (P<0.0001), the drug
      (P<0.0001) and their interaction (P<0.0001), demonstrating antagonism. No
      interaction was present for morphine plus NSAIDs. The results demonstrate that
      NSAIDs antagonise the constipating effects of tramadol in rats, a fact that could
      have clinical relevance when combinations of these drugs are used in pain
      management in humans.

PMID- 14660027
TI  - Pharmacological profile of phytoestrogens in cerebral vessels: in vitro study
      with rabbit basilar artery.
AB  - As a previous step to consider their use in the pharmacology for stroke, we
      investigated the effects of four phytoestrogens (i.e. genistein, daidzein,
      zearalanone and biochanin A) on cerebral vessels. Cerebral vascular responses
      were analyzed by conventional recording of isometric tension in rabbit basilar
      artery segments kept in organ bath under standard conditions. The four
      phytoestrogens elicited concentration-dependent relaxant responses of different
      potency in basilar artery segments previously contracted with either 5x10(-2) M
      KCl or 10(-4) M UTP. Neither endothelium removal, 10(-4) M N(omega)-nitro-L
      arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), 10(-5) M1 H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, selective inhibitor of NO
      sensitive guanylyl cyclase), 10(-5) M 4H-8-bromo-1,2,4-oxadiazolo(3,4
      d)benz(b)(1,4)oxazin-1-one (NS2028, specific soluble guanylyl cyclase inhibitor),
      nor 10(-5) M indomethacin (prostaglandin biosynthesis inhibitor) modified the
      phytoestrogen-elicited vasorelaxant responses. On the other hand, Ca(2+)-elicited
      contractile responses were effectively inhibited in the presence of
      phytoestrogens. Phytoestrogens act as cerebrovascular relaxants by a mechanism
      which involves Ca(2+) entry blockade in the vascular smooth muscle rather than
      stimulation of vasorelaxant endothelium-related mechanisms such as NO/cGMP or
      prostaglandins.

PMID- 14660028
TI  - Characterization of beta 3-adrenoceptor-mediated relaxation in rat abdominal
      aorta smooth muscle.
AB  - The present study was carried out to characterize beta-adrenoceptor subtypes
      mediating relaxation of rat abdominal aorta smooth muscle. (-)-Isoprenaline and a
      nonconventional beta(3)-adrenoceptor agonist, (+/-)-[4-[3-[(1,1
      dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one]
      hydrochloride ((+/-)-CGP12177A), induced concentration-dependent relaxation of (
      )-phenylephrine (0.3 microM) preconstricted spiral preparations. Pretreatment
      with a combination of (+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4
      (trifluoromethyl)-1H-imidazol-2-yl]phenoxy]propyl]amino]ethoxy]-benzamide
      methanesulfonate (CGP20712A, a selective beta(1)-adrenoceptor antagonist) and (+/
      )-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol
      hydrochloride (ICI-118,5511, a selective beta(2)-adrenoceptor antagonist) (0.1
      microM for each) produced a 14-fold rightward shift of the concentration-response
      curve for (-)-isoprenaline; however, the relaxation in response to (+/-)
      CGP12177A was unaffected by the blockade of beta(1)- and beta(2)-adrenoceptors.
      In the presence of CGP20712A and ICI-118,551 (0.1 microM for each), the
      concentration-response curves for (-)-isoprenaline and (+/-)-CGP12177A were
      shifted to the right by a nonselective beta(1)-, beta(2)- and beta(3)
      adrenoceptor antagonist, (+/-)-bupranolol (3 and 10 microM). These results
      clearly suggest that beta(3)-adrenoceptors are involved in beta-adrenoceptor
      mediated relaxation of rat abdominal aorta smooth muscle.

PMID- 14660029
TI  - Carvedilol improves energy production during acute global myocardial ischaemia.
AB  - Cardiac mitochondria may become dysfunctional during ischaemia, thus compromising
      cardiomyocyte function. Carvedilol is an alpha(1)/beta-adrenoceptor antagonist
      with antioxidant, neuroprotective, cardioprotective and vascularprotective
      properties, and is used to treat hypertension, myocardial ischaemia and
      congestive heart failure. However, its impact on mitochondrial function during
      acute prolonged ischaemia is unknown. We aimed to study the effect of carvedilol
      on cardiac mitochondrial function during acute ischaemia, using Wistar rat hearts
      perfused with a Langendorff system, and then submitted to ischaemia in the
      presence and absence of carvedilol. We determined the electrical potential of the
      mitochondrial membrane, O(2) consumption by the respiratory chain, energy charge
      and the activity of the mitochondrial respiratory chain complexes. In our model,
      carvedilol had a preferential action on phosphorylation, increasing the
      mitochondrial energy charge (0.76+/-0.03 vs. 0.65+/-0.01 arbitrary units; P<0.05)
      and decreasing the phosphorylation lag phase (28.64+/-4.23 vs. 62.4+/-11.63 s;
      P<0.05) during ischaemia. The larger amount of energy available allowed the
      preservation of the electrical potential (201.2+/-2.45 vs. 186.66+/-3.36
      mV;P<0.05), thus improving mitochondrial function during acute prolonged
      ischaemia.

PMID- 14660030
TI  - Alpha 1-adrenoceptor subtypes mediating noradrenaline-induced contraction of
      pulmonary artery from pulmonary hypertensive rats.
AB  - The effect of monocrotaline-induced pulmonary hypertension on alpha(1)
      adrenoceptor-mediated contractions of pulmonary artery segments was studied. In
      control and monocrotaline-treated rats, noradrenaline evoked concentration
      dependent contractions of the pulmonary artery. There was no change in the
      potency and affinity of noradrenaline but the maximum response and receptor
      reserve were significantly reduced. Noradrenaline-induced contractions were
      competitively antagonized by prazosin, 2-(2-6dimethoxyphenoxyethyl)aminomethyl
      1,4-benzodioxane hydrochloride (WB 4101) and 8-[2-[4-(2methoxyphenyl)-1
      piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9 dione dihydrochloride (BMY 7378)
      with pA(2) values of 9.64+/-0.16, 9.45+/-0.10 and 8.30+/-0.14, respectively.
      These antagonists also competitively antagonized noradrenaline-induced
      contractions of pulmonary artery segments isolated from rats with monocrotaline
      induced pulmonary hypertension. The pA(2) values were 9.66+/-0.11 (prazosin),
      9.62+/-0.09 (WB 4101) and 8.47+/-0.15 (BMY 7378). Chloroethylclonidine (CEC)
      shifted noradrenaline concentration-response curve to the right and depressed the
      maximum response. There was no difference between the effects of CEC in both
      groups. It was therefore concluded that pulmonary hypertension significantly
      reduced noradrenaline-induced contractions of the rat pulmonary artery without
      affecting the sensitivity. Studies with receptor-selective antagonists confirmed
      that alpha(1)D-adrenoceptor subtype is the predominant receptor subtype in the
      pulmonary artery and this was maintained in this disease state.

PMID- 14660031
TI  - Platelet inhibitory effects of the nitric oxide donor drug MAHMA NONOate in vivo
      in rats.
AB  - The platelet inhibitory effects of the nitric oxide (NO) donor drug MAHMA NONOate
      ((Z-1-[N-methyl-N-[6-(N-methylammoniohexyl)amino]]diazen-1-ium-1,2-diolate) were
      examined in anaesthetised rats and compared with those of S-nitrosoglutathione
      (GSNO; an S-nitrosothiol). Bolus administration of the aggregating agent ADP dose
      dependently reduced the number of circulating free platelets. Intravenous
      infusions of MAHMA NONOate (3-30 nmol/kg/min) dose-dependently inhibited the
      effect of 0.3 micromol/kg ADP. MAHMA NONOate was approximately 10-fold more
      potent than GSNO. MAHMA NONOate (0.3-10 nmol/kg/min) also reduced systemic artery
      pressure and was again 10-fold more potent than GSNO. Thus MAHMA NONOate has both
      platelet inhibitory and vasodepressor effects in vivo. The dose ranges for these
      two effects overlapped, although blood pressure was affected at slightly lower
      doses. The platelet inhibitory effects compared favourably with those of GSNO,
      even though NONO-ates generate free radical NO which, in theory, could have been
      scavenged by haemoglobin. Therefore platelet inhibition may be a useful
      therapeutic property of NONOates.

PMID- 14660032
TI  - Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by
      ischemia/reperfusion of the rat kidney.
AB  - Dithiocarbamates can modulate the expression of genes associated with
      inflammation or development of ischemia/reperfusion injury. Here, we investigate
      the effects of pyrrolidine dithiocarbamate, an inhibitor of nuclear factor (NF)
      kappaB activation, on the renal dysfunction and injury caused by
      ischemia/reperfusion of the rat kidney. Bilateral clamping of renal pedicles (45
      min) followed by reperfusion (6 h) caused significant renal dysfunction and
      marked renal injury. Pyrrolidine dithiocarbamate (100 mg/kg, administered i.v.)
      significantly reduced biochemical and histological evidence of renal dysfunction
      and injury caused by ischemia/reperfusion of the rat kidney. Furthermore,
      pyrrolidine dithiocarbamate markedly reduced the expression of inducible nitric
      oxide synthase (iNOS) protein and significantly reduced serum levels of nitric
      oxide. Finally, pyrrolidine dithiocarbamate inhibited the activation of NF-kappaB
      by preventing its translocation from the cytoplasm into the nuclei of renal
      cells. These results demonstrate that pyrrolidine dithiocarbamate reduces renal
      ischemia/reperfusion injury and that dithiocarbamates may provide beneficial
      actions against ischemic acute renal failure.

PMID- 14660033
TI  - Anti- and prooxidant effects of chronic quercetin administration in rats.
AB  - The present study was performed to investigate the effects of chronic
      administration of quercetin on lipid peroxidation and glutathione concentration
      in rat liver. Male Sprague-Dawley rats were divided into two groups, one of which
      was fed a normal diet and the other a vitamin E-free diet. Each of these groups
      was divided further into three subgroups and treated with quercetin administered
      orally at either 2 or 20 mg/day or with vehicle for 4 weeks. The concentrations
      of alpha-tocopherol in serum and liver increased following quercetin treatment,
      and these increases were significantly greater in rats maintained on a vitamin E
      free diet. Quercetin significantly decreased the concentration of malondialdehyde
      (an indicator of lipid peroxidation) in the liver and this decrease was more
      pronounced in vitamin E-deprived rats than in those maintained on a normal diet
      (55-60% and 25-35% decrease in malondialdehyde concentrations, respectively).
      Quercetin treatment decreased the glutathione concentration and glutathione
      reductase activity (40 and 34%, respectively) in the liver significantly and to a
      similar extent in vitamin E-deprived and -undeprived rats. Collectively, these
      results suggest that quercetin may act not only as an antioxidant, but also as a
      prooxidant in rats.

PMID- 14660034
TI  - The effects of MCC-134 on the ATP-sensitive K+ channels in pig urethra.
AB  - We have investigated the effects of MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N
      methyl-cyclobutanecarbothioamide) on membrane currents and ATP-sensitive K(+)
      channel (K(ATP) channel) opener-induced currents in pig urethra by use of patch
      clamp techniques (conventional whole-cell configuration and nystatin perforated
      patch recordings). Tension measurement was also performed to study the effects of
      MCC-134 on the resting tone of pig urethral strips. MCC-134 reduced the resting
      tone of pig urethra in a concentration-dependent manner (EC(50)=6 microM). The
      MCC-134 (30 microM)-induced relaxation was suppressed by glibenclamide. In
      voltage-clamp experiments, MCC-134 produced a concentration-dependent inward K(+)
      current which was suppressed by application of glibenclamide at a holding
      potential of -50 mV (symmetrical 140 mM K(+) conditions). Application of MCC-134
      enhanced diazoxide-induced inward currents and inhibited pinacidil-induced inward
      currents in a concentration-dependent manner at -50 mV. These results suggest
      that MCC-134 induces glibenclamide-sensitive K(ATP) currents in pig urethra.

PMID- 14660035
TI  - Emetic action of the prostanoid TP receptor agonist, U46619, in Suncus murinus
      (house musk shrew).
AB  - The emetic action of the prostanoid TP receptor agonist, 11alpha,9alpha
      epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619; 300 microg/kg, i.p.),
      was investigated in Suncus murinus. The emetic response was reduced by 76%
      following bilateral abdominal vagotomy (P<0.001) and by reserpine (5 mg/kg, i.p.,
      24 h pretreatment; P<0.05) but U46619 administered i.c.v. (30-300 ng) was not
      emetic, suggesting a peripheral mechanism involving monoamines. However,
      fenfluramine (5 mg/kg, repeated treatment) and para-chlorophenylalanine (100-400
      mg/kg) and ondansetron (0.3-3 mg/kg) were inactive (P>0.05) to reduce U46619
      induced emesis precluding a role of 5-HT and 5-HT(3) receptors in the mechanism.
      Similarly, phentolamine (0.3-3 mg/kg), propranolol (3 mg/kg), and their
      combination, and metoclopramide (0.3-3 mg/kg), domperidone (0.3-3 mg/kg),
      droperidol (0.3-3 mg/kg), scopolamine (0.3-3 mg/kg) and promethazine (0.3-3
      mg/kg) were inactive (P>0.05) to reduce the retching and vomiting response.
      However, the tachykinin NK(1) receptor antagonist, (+)-2S,3S(-3-(2-methoxy-5
      trifluoromethoxybenzyl)amino-2-phenylpiperidine) (CP-122,721; 1-10 mg/kg)
      antagonized emesis (P<0.01). In conclusion, U46619-induced emesis appears to be
      mediated via a predominant peripheral mechanism sensitive to reserpine and is not
      likely to involve adrenoceptors, dopamine, 5-HT(3), muscarinic or histamine
      (H(1)) receptors. The action of CP-122,721 to reduce U46619-induced emesis
      extends the spectrum of anti-emetic action tachykinin NK(1) receptor antagonists
      to mechanisms involving TP receptors.

PMID- 14660036
TI  - Biphasic response of cutaneous blood flow induced by passive cutaneous
      anaphylaxis in rats.
AB  - In the immediate phase of passive cutaneous anaphylaxis, sensitized skin mast
      cells release various mediators when activated by antigen. The present study
      investigated the effects of the mediators on cutaneous blood flow at the antigen
      antibody reaction site. Induction of passive cutaneous anaphylaxis produced a
      biphasic response consisting of an initial decrease, followed by a sustained
      increase, in the cutaneous blood flow. The initial phase was almost eliminated by
      the 5-hydroxytryptamine receptor antagonist methysergide, whereas the second
      phase was sensitive to the histamine H(2) receptor antagonist ranitidine. The
      histamine H(1) receptor antagonist chlorpheniramine, the denervation of sensory
      nerves with capsaicin, the cyclooxygenase inhibitor indomethacin, or the
      bradykinin B(2) receptor antagonist D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy
      L-prolylglycyl-3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3
      isoquinolinecarbonyl-L-(2alpha,3beta,7abeta)-octahydro-1H-indole-2-carbonyl-L
      arginine (HOE140) did not affect the blood-flow changes caused by the
      anaphylaxis. These results suggest that 5-hydroxytryptamine and histamine H(2)
      receptors mediate the initial decrease and the subsequent increase in cutaneous
      blood flow, respectively, induced by passive cutaneous anaphylaxis in rats.

PMID- 14660037
TI  - A comparative study of intratympanic steroid and NO synthase inhibitor for
      treatment of cochlear lateral wall damage due to acute otitis media.
AB  - We studied the damage to the cochlear lateral wall induced by otitis media and
      the therapeutic effects of intratympanic administration of steroid and nitric
      oxide (NO) synthase inhibitor. In Sprague-Dawley rats, right middle ear cavities
      were inoculated with lipopolysaccharide, followed after 30 min by intratympanic
      administration of dexamethasone, NOS-inhibitor or PBS. Twenty-four hours after
      lipopolysaccharide inoculation, cochlear blood flow was measured by laser-Doppler
      flowmetry. Prostaglandin E(1) was topically applied to the round window membrane
      of the right ear and changes in cochlear blood flow were calculated. Changes of
      cochlear blood flow were significantly different among the three groups.
      Increases in cochlear blood flow following PGE(1) application were higher in the
      group that received NOS-inhibitor. Electron microscopic examination revealed that
      changes in the stria vascularis were less severe in rats treated with
      dexamethasone or NOS-inhibitor. Our results show the effectiveness of
      intratympanic dexamethasone or NOS-inhibitor in treating cochlear lateral wall
      damage caused by otitis media.

PMID- 14660038
TI  - Effects of a mitogen-activated protein kinase inhibitor on allergic airways
      inflammation in the rat studied by magnetic resonance imaging.
AB  - We recently described a new model to study non-invasively with magnetic resonance
      imaging (MRI) the effects of compounds to prevent and/or resolve airway
      inflammation induced by ovalbumin in the lungs of actively sensitised rats. We
      report here the effects of 4-(4-fluorophenyl)-2-(1-methylpiperidin-4-yl)-5-(2-(1
      (S)-phenylethyl)amino-4-pyridinyl)thiazole fumarate (Compound 1), which exhibits
      inhibitory activity against p38alpha and p38beta2 and residual activity on c-Jun
      amino-terminal kinase (JNK)2 mitogen-activated protein (MAP) kinases, on the
      oedematous signals detected by MRI and generated by antigen challenge in the
      lungs of sensitized rats. Compound 1 (10 mg kg(-1)) given orally 1 h prior to
      allergen challenge significantly reduced the oedematous signal measured at 24 h.
      Similar effects were seen with a synthetic corticosteroid, mometasone furoate
      (0.3 mg kg(-1)), given intratracheally 3 h prior to challenge. For both
      compounds, inhibition of the oedematous signal was accompanied by reductions in
      the inflammatory parameters in the bronchoalveolar lavage fluid measured 24 h
      after challenge with ovalbumin. Compound 1 (10 mg kg(-1)) administered 24 h after
      challenge with ovalbumin did not change the rate of resolution of the signal
      detected by MRI in the lungs. In contrast, mometasone furoate (0.3 mg kg(-1))
      significantly increased resolution of these signals, which was evident 3 h after
      drug administration and maintained to 48 h post challenge. Collectively, our data
      suggest that the p38 MAP kinase inhibitor Compound 1 shows a different profile
      than glucocorticosteroids since its ability to resolve existing inflammation is
      limited.

PMID- 14660039
TI  - Inhibition of lipopolysaccharide/ATP-induced release of interleukin-18 by KN-62
      and glyburide.
AB  - Monocytes release interleukin-18 after activation by lipopolysaccharide/ATP.
      Since inflammatory conditions such as sepsis are characterized by augmented
      interleukin-18 in sera of patients, we sought to modulate lipopolysaccharide/ATP
      induced interleukin-18 release by pharmacological means. Here we report that 1
      [N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62),
      an inhibitor of ATP-mediated cellular activation by the purinoreceptor subtype
      P(2x7), potently suppresses interleukin-18 release from peripheral blood
      mononuclear cells. Interleukin-18 liberation was likewise inhibited by glyburide,
      a modulator of ion transport and inhibitor of ATP-binding cassette transporter 1.
      The data presented herein indicate that by pharmacologically interfering with the
      process of cytokine secretion agents such as KN-62 or glyburide have the
      potential to curb overproduction of interleukin-18 in septic patients.

PMID- 14660040
TI  - Oestradiol and mirtazapine restore the disturbed tail-temperature of oestrogen
      deficient rats.
AB  - The purpose of the present study was to further evaluate the tail-temperature
      test as a tool to test potential steroidal and non-steroidal compounds for the
      treatment of hot flushes. Ovariectomized rats were implanted with a temperature
      sensitive probe. After a recovery period of 5 weeks, the effect of oestradiol
      (given via a silastic tube) and the 5-HT(2) receptor antagonist mirtazapine (10
      mg/kg i.p.) on the tail-temperature in the active phase of the animals was
      measured. Oestradiol completely restored the disturbed tail temperature after 3
      days. Treatment with mirtazapine also restored the oestrogen withdrawal-induced
      disturbed tail-temperature. The effect of mirtazapine was already seen on the
      first day of treatment. These experiments confirm and extend the idea that
      measuring the oestradiol withdrawal-induced disturbance of tail-temperature may
      be a useful tool to select compounds that might have beneficial effects in the
      treatment of hot flushes. Blockade of the 5-HT(2A) receptors prevented or reduced
      the ovariectomy-induced disturbance of the rat tail-temperature, which may
      validate this model to evaluate the effect of compounds on hot flushes.

PMID- 14660041
TI  - Spiro[9,10-dihydroanthracene]-9,3'-pyrrolidine-a structurally unique tetracyclic
      5-HT2A receptor antagonist.
AB  - Structural elaboration of phenylethylamine to spiro[9,10-dihydroanthracene]-9,3'
      pyrrolidine (SpAMDA) produces an agent with unexpectedly high affinity (K(i)=4
      nM) at 5-HT(2A) receptors. It was shown that SpAMDA acts as a 5-HT(2A) receptor
      antagonist. The structure and molecular geometry of SpAMDA are not consistent
      with existing pharmacophore features, and a novel 5-HT(2A) antagonist
      pharmacophore model is proposed for the binding of aminomethyl-9,10
      dihydroanthracene analogs. Thus, SpAMDA may be a structurally novel parent of a
      new class of 5-HT(2A) receptor antagonists that binds to the receptor in a unique
      fashion that is distinct from the binding topology of existing 5-HT(2A) receptor
      antagonists.

PMID- 14660042
TI  - Heat increases 3,4-methylenedioxymethamphetamine self-administration and social
      effects in rats.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a drug frequently used
      under hot conditions in nightclubs. In rats tested in the social interaction
      paradigm, greater prosocial effects of MDMA (5.0 mg/kg) were seen at a hot
      temperature (30 degrees C) relative to normal laboratory temperature (21 degrees
      C). In the intravenous drug self-administration paradigm, hot temperature (30
      degrees C) increased the number of MDMA infusions (0.1, 0.3 or 1.0
      mg/kg/infusion) self-administered by rats. Hot temperatures thus appear to affect
      both the social and reinforcing effects of MDMA.

PMID- 14660043
TI  - Purification of human natural killer cells using a clinical-scale immunomagnetic
      method.
AB  - BACKGROUND: Infection, graft failure, disease relapse, and GvHD are significant
      adverse events associated with allogeneic BMT. Although donor leukocyte infusion
      has been used to prevent or to treat infection, graft failure, and relapse, the
      potential clinical benefits are often outweighed by the risk of T cell-mediated
      GvHD. Results from animal studies suggest that donor natural killer (NK) cells
      may be an ideal cell type for prevention or treatment of these adverse events. We
      have therefore sought to develop an automated, efficient, and clinical-scale
      human NK cell-purification method. METHODS: Twelve leukopheresis products were
      purified for NK cells using a two-step immunomagnetic method. CD3(+) cells were
      first depleted from the apheresis products. CD56(+) cells were then enriched from
      the CD3(+) cell-depleted products. RESULTS: The median percentage of CD3(
      )CD56(+) NK cells in the final products was 91.0%, and the median recovery was
      48.7%. The median depletion for CD3(+)CD56(-) T cells was 5.3 log. Natural
      cytotoxicity of the purified cells was approximately five-fold higher than that
      of unpurified mononuclear cells, and it could be further increased by stimulation
      of the purified cell with IL2. DISCUSSION: We described a large-scale
      purification method for automated, efficient, and rapid isolation of human NK
      cells that yielded minimal contamination with T cells or B cells. These purified
      NK cells may be expedient for preclinical and clinical uses.

PMID- 14660044
TI  - Immunomodulatory effects of fetal and adult mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) derived from adult BM or fetal liver form several
      mesenchymal tissues after appropriate stimulation. Reports indicate that MSC have
      unique immunologic properties, making them ideal for cellular therapy. MSC are
      not immunogenic, they do not stimulate alloreactivity, and they escape lysis by
      cytotoxic T-cells and natural killer (NK)-cells. Thus, MSC may be transplantable
      between HLA-mismatched individuals without the need for host immunosuppression.
      Furthermore, adult MSC appear to be immunosuppressive as they reduce
      alloreactivity and the formation of cytotoxic lymphocytes in vitro. In vivo,
      adult MSC prolong the time to rejection of mis-matched skin grafts in baboons.
      The immunosuppressive properties of first trimester fetal MSC are less
      pronounced, but inducible with IFNgamma. These findings imply a potential role
      for MSC, not only in the repair of damaged tissues, but also in the manipulation
      of immune responses.

PMID- 14660045
TI  - Expansion of HPCs from cord blood in a novel 3D matrix.
AB  - BACKGROUND: An optimal system for the expansion of pluripotent HPCs would ideally
      eliminate the use of cytokines and animal-derived serum. We have shown previously
      that a 3D, tantalum-coated porous biomaterial (Cytomatrix) supports the
      maintenance and expansion of human BM HPCs in the absence of cytokines. METHODS:
      Umbilical cord blood (UCB) derived HPC were cultured in the Cytomatrix in the
      absence of exogenous cytokines. Phenotype was determined using FACS. Colony
      forming units (CFU) activity was evaluated. Engraftment capacity was evaluated by
      transplanting the expanded cells into non-obese diabetic (NOD)/SCID mice.
      RESULTS: We describe the expansion of HPCs from UCB using the Cytomatrix system.
      When UCB-derived CD34(+) cells were cultured in the Cytomatrix system for 2 weeks
      we observed an increase in the number of nucleated cells (3-fold) and CFU (2.6
      fold). The number of CD45(+) and CD34(+) cells both increased three-fold. Trends
      demonstrated an increase in the frequency of CD34(+)C38(-) cells, and an increase
      in both CD34(+)C33(+) cells and CD34(+)C61(+) cells. No expansion of T or B
      lymphocytes was observed. When expanded UCB cells from the Cytomatrix were
      injected into sub-lethally irradiated NOD/SCID mice, human cells were detected in
      the murine peripheral blood and BM 6 weeks post-transplantation. DISCUSSION: This
      unique approach to the expansion of UCB cells in a serum-free, cytokine-free
      environment may provide expansion of HPCs with multi-lineage engraftment
      capability that could be used clinically.

PMID- 14660046
TI  - Kinetics of quiescent cord blood stem/progenitor cells with high proliferative
      potential in stem-cell expansion culture.
AB  - BACKGROUND: The most primitive engrafting hematopoietic stem cell (HSC) resides
      mainly in a tumor growth factor-beta (TGF-beta)-dependent quiescent phase of the
      cell cycle. In this study, ex vivo expansion of UC blood (UCB) HSCs has been
      investigated, with the aim of showing whether quiescent HSCs can be recovered
      from expansion culture. METHODS: AC133(+) stem/progenitor cells from six full
      term-pregnancies UCB-samples were immunomagnetically selected, followed by ex
      vivo expansion culture in the presence of thrombopoietin (TPO), c-kit ligand
      (KL), flt-3 ligand (FL) and IL-6. Quiescent HSCs were detected by a clonogenic
      assay that allows the detection of multipotent and committed single- lineage
      quiescent stem/progenitor cells, named mHPP-Q and cHPP-Q, respectively, by means
      of a TGF-beta blocking Ab. RESULTS: Expansion culture of fresh selected AC133(+)
      cells for 1 week caused maintenance rather than expansion of mHPP-Q cells and a 1
      fold increase in cHPP-Q cells. A further week culture initiated with 7-day
      expanded AC133(+) cells resulted in an additional 1.5-fold expansion of cHPP-Q
      while no mHPP-Q cells could be detected. Amplification of cHPP-Q cells in long
      term expansion cultures initiated with 14-day expanded AC133(+) cells was
      observed for at least a further 4 weeks. DISCUSSION: A small proportion of HPP-Q
      cells recovered from 7-day expansion cultures retain their multilineage
      potential: longer culturing of these cells results in the loss of multilineage
      potential while they maintain quiescent behavior and high proliferative
      potential.

PMID- 14660047
TI  - Delivery of herpes simplex thymidine kinase bystander effect by engineered human
      mesothelial cells for the treatment of ovarian cancer.
AB  - BACKGROUND: Resistance to conventional chemotherapy is a major clinical problem
      for ovarian cancer, and long-term survival for patients with advanced-stage
      disease is rare. Other therapeutic strategies, such as gene therapy, have been
      explored but several limitations exist, which include low viral vector
      transduction efficiency, host immune response to the vector, and vector toxicity.
      METHODS: We developed a cell-based therapy that exploits human mesothelial cells
      to deliver anticancer modalities for treatment of ovarian cancer. As a proof of
      concept, we genetically engineered mesothelial with the herpes simplex virus
      thymidine kinase/ganciclovir (HSVTK/GCV) system to deliver cytotoxicity to human
      ovarian cancer cells. This system is well characterized, and has been widely used
      in different gene-therapy based strategies. RESULTS: Our results demonstrate that
      HSVTK-modified mesothelial cells are sensitive to GCV killing in vitro and
      support the HSVTK bystander effect. Engineered mesothelial cells can deliver the
      HSVTK bystander effect to human ovarian cancer cell-lines, as well as to primary
      ovarian cancer cells. A significant reduction of tumor growth and prolongation of
      survival in s.c. and i.p. xenograft mouse models of ovarian cancer are obtained
      with as little as 1% of HSVTK-expressing mesothelial cells. Intraperitoneal
      administration of HSVTK-expressing mesothelial cells in an established mouse
      model of ovarian cancer results in a statistically significant prolonged survival
      of treated animals. Importantly, distribution studies showed that mesothelial
      cells localize preferentially to tumor sites. DISCUSSION: Our study demonstrates
      the feasibility of using a mesothelial cell-based therapy for treatment of
      ovarian cancer, and suggests that this strategy should be further explored.

PMID- 14660048
TI  - Transplanted BM and BM side population cells contribute progeny to the lung and
      liver in irradiated mice.
AB  - BACKGROUND: BM cells have been shown to give rise to progeny of various cell
      lineages, including cells in lung and liver. This investigation evaluated whether
      purified BM mononuclear cells and side population (SP) cells that have
      hematopoietic stem-cell activity also had this property; whether a TBI
      preparative regimen was necessary for engraftment; and where BM-derived cells
      were engrafted. METHODS: Either 1-3 million BM mononuclear cells or 2000 BM SP
      cells from transgenic enhanced green fluorescent protein-expressing (EGFP) mice
      were transplanted i.v. to unirradiated or 7-9.5 Gy irradiated recipients.
      RESULTS: Flow cytometric analysis showed that lung cells (mean 45%, range 4-70%)
      and liver cells (mean 4%, range 0.4-8.3%) from irradiated, but not unirradiated
      recipients, were EGFP donor-derived. Similar results were obtained transplanting
      BM mononuclear cells or SP cells. Morphologically, donor-derived cells in the
      lung were primarily monocytes and macrophages. Additionally, lung fibroblasts and
      Type I, but not Type II, alveolar cells and rare cells in the bronchial
      epithelium were donor BM derived. In the liver, Kupffer cells, inflammatory cells
      and small clusters of hepatocytes, but not bile duct cells, were donor-derived.
      DISCUSSION: BM mononuclear and SP cells generated progeny in some compartments of
      the lung and liver, but only in TBI recipients. Stem cells in BM can contribute
      to repair of tissue injury in some compartments, but not to the same extent in
      the lung and liver.

PMID- 14660049
TI  - Selected CD34 blood cell allografts for older patients: low transplant-related
      mortality, graft failure and acute GvHD.
AB  - BACKGROUND: Early transplant mortality is related to acute GvHD, which this study
      in older patients (40 to 60 years) decreased by reducing the graft T-cell number
      while maintaining a high CD34 cell number--by positive CD34 cell selection.
      Potential increased risk of relapse is addressed by giving donor leucocyte
      infusion (DLI) post-transplant. METHODS: CD34 cells selected by Isolex devices
      from leukophereses obtained from Filgrastim-treated matched sibling donors were
      transplanted and DLI given later if there was no GvHD. RESULTS: Selection of CD34
      cells achieved a median of 5.2 million cells/kg, with minimum target for
      transplantation achieved in 17 of 21 donors. Median CD3 cell number was 0.24
      million/kg. Engraftment was rapid and graft failure rare. Transplant-related
      mortality was low (6% at 3 months). Acute GvHD of >or=Grade 2 occurred in only
      two patients (12.5%). DLI were given to only six patients who had resolved Grade
      1 or no GvHD. Eight of the 17 patients relapsed, including three of the six who
      had DLI. Extensive chronic GvHD developed in six of 12 evaluable patients, two of
      these had received DLI. Seven of the 17 patients (41%) are alive at median follow
      up of 56 months. CONCLUSION: CD34 selection allows transplantation of high
      numbers of CD34 cells with low CD3 cell count, reducing early mortality in
      patients 40-60 years old because of rapid hemopoietic reconstitution and low
      acute GvHD incidence. Administration of DLI was often precluded by low-grade
      acute GvHD.

PMID- 14660050
TI  - Immunological and clinical effects of post-transplant G-CSF versus placebo in T
      cell replete allogeneic blood transplant patients: results from a randomized
      double-blind study.
AB  - BACKGROUND: Immunological and clinical effects of post-transplant growth factor
      administration have not been well studied. This report describes the outcome and
      immune functions of a total of 50 HLA-matched related donor allogeneic blood stem
      cell transplantation patients who received post-transplant G-CSF (10 microg/kg)
      or placebo. METHODS: Immune status, including number of lymphocyte subsets and
      their functions, and serum immunoglobulin levels and clinical status--including
      GvHD, rate of relapse, event-free survival, and overall survival--were determined
      in the patients enrolled in this study. RESULTS: Twenty-eight patients survived 1
      year after transplant, and 15 patients had available results to compare immune
      function by randomization assignment. At 12 months post-transplant, immune
      parameters in G-CSF versus placebo groups showed no statistically significant
      differences in number of circulating lymphocyte subsets CD3, CD4, CD8, CD19 and
      CD56 in the two groups. There was no significant (NS) difference in
      immunoglobulin IgG, IgA and IgM levels, NK or LAK cell-mediated cytotoxicity
      levels, and mitogen-induced proliferation between post-transplant G-CSF and
      placebo group. In addition, the analyses of immune parameters at earlier time
      points on Days 28, 100, 180, and 270 revealed that, except for LAK cytotoxicity
      at Day 100, there was no differences between the two groups. Fourteen of 26
      patients are alive in the G-CSF arm and nine of 24 in the placebo arm. Median
      follow-up of surviving patients is 43 months. Four year overall and event-free
      survival in the G-CSF and the placebo group were 53% and 35% (NS), and 44% and
      36% (NS) respectively. Bacterial or fungal infections were the cause of six of 12
      deaths in the G-CSF arm (all bacterial) and of four of 15 deaths in the placebo
      arm (two deaths from Aspergillus) (P=0.26). Two patients relapsed in the G-CSF
      arm and three in the placebo arm. Four year cumulative incidences of relapse were
      8% versus 13% in G-CSF versus placebo arms, respectively, (NS). Chronic GvHD
      developed in 14 of 19 100-day survivors after G-CSF (11 extensive stage), and in
      17 of 20 (14 extensive stage) in the placebo arm. The 4-year cumulative incidence
      of chronic GvHD was 56% [95% confidence interval (CI) 24-88%] after G-CSF and 71%
      (95% CI 48-94%) after placebo; this difference was not statistically significant
      (log rank P=0.41). CONCLUSION: In summary, there were no significant
      immunological or alterations in clinical benefit of post-transplant G-CSF
      administration in T-replete allotransplant recipients.

PMID- 14660052
TI  - Recent advances in stem cell transplantation. Abstracts from the 11th
      International Symposium. Del Mar, California, USA. May 8-10, 2003.

PMID- 14660051
TI  - Inverted spin method for removing RBCs from BM buffy coat products.
AB  - BACKGROUND: Inverted spin is a method of removing RBCs that historically has been
      part of blood banking practice. We investigated the feasibility of using this
      method for RBC depletion of BM buffy coat products in situations where recipient
      RBC Abs have been identified to donor RBC Ags. METHODS: The BM buffy coat product
      was placed in a transfer pack, inverted, centrifuged at 600 g for 10 min,
      suspended and the RBCs removed slowly into another transfer pack. Nine patients
      treated between April 1998 and February 2001 received products prepared by our
      version of the inverted spin procedure. RESULTS: We removed a median value of
      81.2% of the RBCs, while still recovering a median of 94.3% of the mononuclear
      cells (median: 0.35 x 10(8)/kg; range: 0.17-0.9 x 10(8)/kg). The median volume of
      RBCs remaining in the product was 15.0 mL (range: 7.3-21.9 mL). The CD34(+) cell
      dose of the final product ranged from 1.0 x 10(6)/kg to 4.8 x 10(6) cells/kg
      (median: 1.9 x 10 6/kg). Granulocyte recovery (defined as ANC count
      >or=500/microL for a period of 3 consecutive days) ranged from 18-30 days post
      infusion of the allograft (median: 24.0 days). One patient died shortly after his
      transplant from complications of his disease. No patient had any evidence of an
      acute hemolytic reaction. DISCUSSION: Advantages of the inverted spin method
      include no need for additives (e.g. hydroxyethyl starch, HSA, or O negative RBC),
      and use of equipment readily available in most processing laboratories.

PMID- 14660053
TI  - Interleukin-12 and interleukin-18 change ICAM-I expression, and enhance natural
      killer cell mediated cytolysis of human osteosarcoma cells.
AB  - Cytokines play important roles in the expression of adhesion molecules and the
      function of anti-tumor effector cells in the immune system. In this study, the
      influence of interleukin-12 (IL-12) and IL-18 on the expression of ICAM-1 and
      natural killer (NK)-cell mediated lysis in a human osteosarcoma cell line (HOS)
      was evaluated. ICAM-I expression of HOS cells were analyzed by flow cytometry
      following treatment with IL-12, IL-18 or both, and in co-cultures with peripheral
      lymphocytes. NK-cell activation in response to IL-12 and IL-18 was investigated
      by selective flow cytometry using propidium iodide. ICAM-1 expression on HOS
      cells was significantly enhanced by IL-12, but only when co-cultured in cell-to
      cell contact with peripheral lymphocytes. Antibodies to interferon-gamma
      abrogated this effect. If HOS cells and peripheral lymphocytes were separated in
      co-cultures, IL-18 could substitute for cell-to-cell contact, facilitating IL-12
      mediated enhancement of ICAM-1. Addition of IL-18 also enhanced NK-mediated
      cytolysis of HOS cells. These findings demonstrate that IL-12 can enhance the
      expression of ICAM-1 in the presence of IFN-gamma and, with IL-18, enhances NK
      anti-tumor activity. Immunomodulation via cytokine therapy may lead to improved
      eradication of chemotherapy-resistant osteosarcomas.

PMID- 14660054
TI  - Increased IFN-gamma synthesis by T cells from patients on imatinib therapy for
      chronic myeloid leukemia.
AB  - Decreased Type 1 cytokine production has been observed in T cells of patients
      with untreated chronic myeloid leukemia (CML). The important role of T cells and
      T-cell cytokines in the long-term control of CML is well established, for example
      in allogeneic stem-cell graft recipients. This study examined whether or not
      molecularly targeted therapy with imatinib, an inhibitor of the BCR-ABL tyrosine
      kinase, improved endogenous T-cell function in patients resistant to or
      intolerant of previous IFN-alpha therapy. Intracellular cytokine staining and
      detection by flow cytometry was used to analyze the expression of the T1 cytokine
      IFN-gamma in T cells. To secure independence from changes in white blood cell
      counts during treatment, a constant number of T cells was purified from the
      peripheral blood before analysis of the proportion of IFN-gamma synthesizing T
      cells. Twenty-nine patients with CML were tested before and after a median follow
      up of 3 month on imatinib. In addition, late follow-up (past the median time to
      best cytogenetic response) of 15 patients were obtained Twenty-nine age- and
      gender-matched individuals were used as healthy controls. The frequency of IFN
      gamma producing T cells in CML patients resistant to or intolerant to previous
      IFN-alpha therapy was lower than in healthy individuals (p=0.0181, Mann-Whitney
      test). Imatinib therapy led to a significant increase over pre-treatment values
      (p<0.0001, Mann-Whitney test). Late follow-up indicated that the increase was
      sustained in patients not in major cytogenetic response. In contrast, in major
      responders levels returned towards values comparable to healthy individuals. In
      conclusion, treatment with imatinib achieves a significant increase in Type 1
      (IFN-gamma) cytokine-producing T cells in patients with CML. This is consistent
      with the view that enhanced T-cell function is achievable in patients with CML,
      even in the absence of allo-mechanisms.

PMID- 14660055
TI  - Serum interleukin-6 concentrations as predictive factor of time to progression in
      metastatic malignant melanoma patients treated by biochemotherapy: a
      retrospective study.
AB  - This retrospective study sought to evaluate the impact of IL-6 concentration on
      time to progression in advanced melanoma. One hundred and thirty-five patients
      were included, serum IL-6 levels were determined before (Day 0), at the end of
      the treatment (Day 49) and at recurrence: the relationship between IL-6
      concentration and time to progression (TTP) was also evaluated. The baseline
      median serum IL-6 level was 16.5 pg/ml. When disease progression was observed, an
      increase in serum IL-6 level was noted. In order to establish the possible
      relationship between IL-6 level and TTP, patients were divided into two groups
      (low and high) using the median IL-6 level (16.5 pg/ml) detected in the
      pretreatment serum of overall patients as a cut-off. Sixty patients were in the
      low IL-6 group and 56 patients in the high IL-6 group. Time to progression was
      calculated from the beginning of treatment to recurrence, and analyzed using the
      Kaplan-Meier method. Patients with low IL-6 serum concentration showed a
      significantly (p<0.00001) higher median TTP than patients with high IL-6 level.
      Patients maintaining a low IL-6 level during the treatment showed the longest
      median TTP compared with those supporting high levels (24.4 versus 5.5 months).
      Taken together, our results showed that serum IL-6 level could be considered a
      predictive marker of recurrent disease in metastatic malignant melanoma.

PMID- 14660056
TI  - Stress, glucocorticoids, and memory: a meta-analytic review.
AB  - Although a strong psychoneuroendocrine linkage exists between stress,
      glucocorticoids and memory, the relationship is not always straightforward.
      Eighty-eight effect sizes and 1642 participants from 28 studies were meta
      analyzed for the effects of stress on memory performance and glucocorticoid
      activation. Analyses showed that stress was associated with glucocorticoid
      activation and declarative memory decline. In animal studies, predator stress
      affected memory performance more than physical stress. In human studies, males
      showed higher cortisol levels than females in response to stress. Further, the
      correlation between cortisol levels and memory deficits was stronger in studies
      using laboratory stressors than those examining long term effects of chronic
      exposure to rising basal levels of glucocorticoids and chronic life stressors. It
      was concluded that, although the relationship between stress, glucocorticoids,
      and memory loss was empirically supported, there were other factors, such as
      stress condition and gender, as well as individual differences within groups,
      that influenced the association between these variables, and warrant further
      examination.

PMID- 14660057
TI  - Stress applied during primary immunization affects the secondary humoral immune
      response in the rat: involvement of opioid peptides.
AB  - The effect of unpredictable, inescapable and uncontrollable electric tail shocks
      (ES) on the humoral immune response to bovine serum albumin (BSA) was
      investigated in the rat. Contributions of the procedures that accompany shock
      delivery, such as witnessing the ES procedure (stress witnessing, SW) and
      exposure to the apparatus for shock delivery (apparatus control, AC) to the
      changes in specific immunity induced by ES were also tested. All procedures were
      applied during primary and/or secondary immunization. It was demonstrated that
      exposure to ES during primary immunization with BSA significantly suppressed
      specific anti-BSA antibody production after secondary and tertiary immunization
      with the same antigen. Exposure to the SW procedure during primary immunization
      with BSA enhanced the specific antibody level after secondary immunization, while
      exposure to the apparatus alone did not influence the development of either the
      primary or secondary humoral immune response to BSA. Both ES-induced suppression
      and SW-induced potentiation of the humoral immune response were partially
      inhibited by prior treatment with the opioid receptor antagonist naloxone.
      Additionally, treatments with the opioid peptides methionine- and leucine
      enkephalin decreased anti-BSA antibody level, mimicking to some extent the
      effects of ES. It is suggested that ES and endogenous opioid peptides had long
      term effects on humoral immunity through mechanisms involving immunologic memory.

PMID- 14660058
TI  - Stressor exposure produces long-term reductions in antigen-specific T and B cell
      responses.
AB  - Exposure to an acute laboratory stressor at the time of keyhole limpet hemocyanin
      (KLH) immunization results in a long-term suppression in circulating anti-KLH
      antibody. The mechanism for the stress-induced reduction in anti-KLH
      immunoglobulin (Ig) remains unknown. Given that the generation of anti-KLH
      antibody requires T cell help, we hypothesize that stress reduces the
      proliferation of anti-KLH T cells, thus leading to a reduction in anti-KLH
      antibody. The present studies examined the effect of tail shock stress (100, 1.6
      mA, 5-s, 60 s ITI) on the KLH specific T cell response. Fischer F344 rats were
      immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) at the base of
      the tail with 200 microg KLH, and exposed to inescapable tail shock (IS) or
      remained in their home cages (HCC). T cell proliferation after KLH restimulation,
      but not ConA, was markedly suppressed in IS animals in both the spleen after i.p.
      immunization and the draining lymph nodes after s.c. immunization. Other
      secondary lymphoid cells did not differ in their proliferative capacity. Anti-KLH
      IgG, IgG1 and IgG2a, but not anti-KLH IgM serum levels were significantly
      suppressed. These data support the conclusion that stress suppresses the
      generation of antigen specific T cells. In addition, the methods employed in the
      current study allow the isolation of the site of the acquired T cell immune
      response, making it possible to further elucidate the cellular mechanisms that
      contribute to stress-induced modulation of the antigen-specific acquired immune
      response.

PMID- 14660059
TI  - Strain and gender specific effects in the forced swim test: effects of previous
      stress exposure.
AB  - The chronic mild stress (CMS) procedure was developed in rodents to target
      anhedonia, the core symptom of depressive melancholia. Stress exposure has been
      shown to induce a variety of physiological, biochemical and behavioral
      alterations associated with depression, although its anhedonic consequences as
      indexed by either sucrose intake and preference or thresholds for brain
      stimulation reward are less reliably observed. In the present study, we assessed
      the effects of six weeks of CMS on the latter measure in two strains of male and
      female rats subsequently challenged with an acute psychophysical stressor, forced
      swimming; their behavior in the swimming cylinder was evaluated on two
      consecutive days. While brain stimulation reward thresholds and response rates
      were unchanged by CMS exposure, significant differences in forced swim behaviors
      were observed between male control and CMS groups. In particular, male Long Evans
      rats with a history of CMS showed the largest decrease in the duration of active
      behaviors on the second test day, a pattern less evident in the Sprague-Dawley
      strain of rats, or in any of the female groups. The results suggest that the
      effects of depressogenic manipulations are strain and gender dependent, with male
      Long Evans rats most susceptible, as demonstrated by the selective reduction of
      struggling behaviors. Inclusion of multiple measures, including the forced swim
      test, would provide a better understanding of the psychopathological profile
      engendered by chronic exposure to mild stressors and its genetic specificity.

PMID- 14660060
TI  - Effects of acute, repeated and chronic variable stress on in vivo tyrosine
      hydroxylase activity and on alpha(2)-adrenoceptor sensitivity in the rat brain.
AB  - We assessed the effects of a single tail pinch and two chronic stress regimes,
      repeated and variable, on in vivo tyrosine hydroxylase activity and on alpha2
      adrenoceptor sensitivity in two brain regions. After administering a 3,4
      dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, tyrosine hydroxylase
      activity, measured as the accumulation of DOPA, and noradrenaline (NA) content
      were determined by using high-performance liquid chromatography. A single tail
      pinch for 5 min induced an enhancement of DOPA content in hippocampus (28%) and
      hypothalamus (67%) which was still present 24 h later. This increase could
      account for the lack of changes in NA content in both regions after the
      application of this stressor. However, tyrosine hydroxylase activity was
      unmodified 24 h after exposure to both repeated (5 min of tail pinch, twice
      daily, for 14 days) and chronic variable stress (one of 5 different stressors,
      once daily, for 14 days) although there was an enhancement of NA levels in
      hippocampus (45 and 54%, respectively) and hypothalamus (24.5 and 36%,
      respectively). The sensitivity of the alpha2-adrenoceptors which regulate [3H]-NA
      release in hippocampal and hypothalamic synaptosomes was not modified by the
      acute or chronic stress protocols assayed. The results show that both paradigms
      of chronic stress had similar effects on the noradrenergic indices evaluated.

PMID- 14660061
TI  - Anxiety in rats selectively bred for Fast and Slow kindling rates: situation
      specific outcomes.
AB  - Rats selectively bred for amygdala excitability, realized by fast or slow
      kindling epileptogenesis, were previously reported to exhibit differential levels
      of anxiety. Although the Slow kindling rats generally appeared more anxious in
      several behavioral tests, under certain test conditions the Fast kindling rats
      displayed greater anxiety or stressor reactivity. The present investigation
      confirmed that in a test of anxiety comprising suppression of consumption of a
      palatable snack in an unfamiliar environment, the Slow kindling rats exhibited
      greater anxiety and that this effect was attenuated by diazepam. Likewise, the
      acoustic startle response was greater in the Slow kindling rats. However, the
      fear-potentiated startle response was more pronounced in Fast kindling rats,
      particularly among females, irrespective of whether the test parameters elicited
      moderate or high startle amplitudes. The elevated startle in the Slow rats, and
      the fear potentiated startle in the Fast rats, were attenuated by diazepam. These
      data indicate the need to differentiate subtypes of anxiety in animal models, and
      raise the issue that anxiety elicited by specific environmental triggers may
      interact with genetically determined trait characteristics.

PMID- 14660062
TI  - Chronic stress accelerates atherosclerosis in the apolipoprotein E deficient
      mouse.
AB  - Conventional cardiovascular risk factors such as cholesterol and blood pressure
      do not account fully for variation in coronary heart disease suggesting the
      involvement of additional mechanisms. We have examined the effects of a chronic
      psychological stress protocol on the development of atherosclerosis in the
      apolipoprotein E knockout mouse. We observed a 3-fold increase in staining for
      atheroma accompanied by a 10-fold increase in corticosterone concentrations in
      mice stressed for 12 weeks. These data suggest that chronic mild stress can
      induce or accelerate the development of atherosclerosis.

PMID- 14660063
TI  - The effect of bupivacaine on compound action potential parameters of sciatic
      nerve fibers.
AB  - The aim of this study was to document the effects of the local anesthetic agent
      bupivacaine on individual fibers of peripheral nerve. To accomplish this
      objective, compound action potentials (CAPs) were recorded from isolated frog
      sciatic nerves treated with bupivacaine for seven individual concentration
      levels. Numerical and fast Fourier transform (FFT) analysis were performed on
      these recordings. The areas, latency periods, maximum and minimum derivatives,
      and power spectrums of the CAPs were computed. The results show that the area and
      the absolute values of maximum and minimum derivatives decrease linearly as
      bupivacaine concentration increases. The power spectrum of the CAPs, which
      resides in the 0-1000 Hz interval, initially shifts to higher frequencies then
      returns to lower frequency region again with increasing bupivacaine
      concentration. Due to this result, it is thought that bupivacaine inhibits nerve
      fibers in a dose-dependent manner. It primarily affects the fibers having the
      least myelin sheets (motor fibers), then it begins to depress the fast conducting
      (neurosensorial) fibers as the bupivacaine concentration increases, and finally
      blocks the unmyelinated C-fibers.

PMID- 14660064
TI  - Agility, gnosis, and graphaesthesia for the toes and fingers in children:
      normative data (ages 7-14 years).
AB  - The differential representation of the toes/feet and fingers/hands along the
      medial and lateral surfaces of the cerebral cortices, respectively, may have
      diagnostic utility. Normative data for errors for toe and finger graphaesthesia
      and gnosis, as well as foot and finger agility, were collected for 86 children
      (ages 7 to 14). The fingers were more agile than the feet, and the right side of
      the body was more agile than the left side, regardless of age. A marked
      improvement in toe gnosis, but not in finger gnosis occurred in children after 11
      12 years of age. A statistically significant interaction between laterality and
      gender was due to the greater numbers of errors for both toe and finger gnosis,
      displayed by girls for the left sides of their bodies compared to their right
      sides. This discrepancy was not significant for boys.

PMID- 14660065
TI  - Massage therapy of moderate and light pressure and vibrator effects on EEG and
      heart rate.
AB  - Three types of commonly used massage therapy techniques were assessed in a sample
      of 36 healthy adults, randomly assigned to: (1) moderate massage, (2) light
      massage, or (3) vibratory stimulation group (n = 12 per group). Changes in
      anxiety and stress were assessed, and EEG and EKG were recorded. Anxiety scores
      decreased for all groups, but the moderate pressure massage group reported the
      greatest decrease in stress. The moderate massage group also experienced a
      decrease in heart rate and EEG changes including an increase in delta and a
      decrease in alpha and beta activity, suggesting a relaxation response. Finally,
      this group showed increased positive affect, as indicated by a shift toward left
      frontal EEG activation. The light massage group showed increased arousal, as
      indicated by decreased delta and increased deta activity and increased heart
      rate. The vibratory stimulation group also showed increased arousal, as indicated
      by increased heart rate and increased theta, alpha, and beta activity.

PMID- 14660066
TI  - Effects of vitamin E and electrical stimulation on the denervated rat
      gastrocnemius muscle malondialdehyde and glutathione levels.
AB  - Effects of vitamin E treatment and local electrical stimulation on progression of
      atrophy in the denervated rat gastrocnemius muscle were studied. Denervation was
      performed by right leg sciatic nerve axotomy. Electrical stimulation (3-10 mA ms(
      1), 10 min per day for 7 days) was applied to the right gastrocnemius muscle
      starting from day 1 of denervation. The muscle samples were assayed for
      malondialdehyde (MDA) and glutathione levels, as well as the histological
      appearance after 8 days of denervation. MDA levels were markedly increased
      following denervation. However, electrical stimulation, vitamin E treatment (30
      mg kg(-1), i.m., everyday for 7 days), and combination of electrical stimulation
      and vitamin E treatment markedly reduced MDA levels. Glutathione levels were
      significantly decreased in the denervation group. Electrical stimulation, vitamin
      E treatment, and electrical stimulation plus vitamin E treatment prevented these
      reductions in glutathione levels. In the vitamin E treatment group, glutathione
      levels were markedly higher than in the control group. These results indicate
      that electrical stimulation and vitamin E treatment alone, or in combination,
      were able to prevent the effects of denervation on muscle atrophy.

PMID- 14660067
TI  - The effect of immobilization stress on sensory gating in mice.
AB  - Central sensory filtering processes can be demonstrated using a paired stimulus
      paradigm. Normal humans show a diminished, vertex-recorded mid-latency (50 ms) of
      auditory evoked potential to the second of paired clicks (0.5 s apart), a
      phenomenon termed as auditory gating. A loss of 50 ms in auditory gating is
      strongly related to psychosis. The N40 auditory evoked potential (EP) in rats has
      been used to develop an animal model for the study of sensory gating mechanisms.
      Previous animal studies of auditory gating have used psychotomimetic drug
      administration to induce sensory gating. However, a nonpharmacologic model of
      deficient gating would be advantageous. In the present study we investigated the
      effect of immobilization stress on sensory gating in twelve adult male mice.
      Evoked responses to the paired auditory click stimuli from vertex location of
      scalp were recorded using a silver needle electrode, a bioelectric amplifier, and
      an analog-digital converter. The mice were exposed to immobilization stress (IS)
      for 3 h. Data showed that the N40 potential was depressed in response to the
      second of the paired stimuli before application immobilization stress. At the end
      of the 3-h immobilization, the depression of the second N40 response was not
      observed. It was concluded that sensory gating is present in the mice and acutely
      disrupted by stressful stimuli, as shown in human subjects and rats.

PMID- 14660068
TI  - Sex and handedness differences in size of cerebral ventricles of normal subjects.
AB  - Sex and handedness differences in the volumes of cerebral ventricles were studied
      in 20 right- and 21 left-handed subjects. To assess the volumes of cerebral
      ventricles, Cavalieri's method was used using MRI. In right-handers, the volume
      of the lateral ventricle was higher in the right side than in the left side, but,
      in left-handers, it was higher in the left side than in the right side. The
      volumes of right-lateral and third ventricles were larger in right-handers than
      in left -handers. There were no sex related differences in terms of the volumes
      of right- and left -lateral, third, and fourth ventricles. These results suggest
      that left-handedness is an important factor reducing the sizes of all the brain
      ventricles.

PMID- 14660069
TI  - N-terminal heterogenicity of amyloid protein examined in Alzheimer's disease.
AB  - Alzheimer's disease is the major cause of dementia in humans. The affected brain
      shows characteristic abnormal filamentous proteins that accumulate
      intracellularly as neurofibrillary tangles, and extracellularly as senile
      plaques, as well as in cerebral blood vessels. The extracellular deposits are an
      amyloid protein, which is highly insoluble. In our study, we intended to show
      that the N-terminus of amyloid A4 protein can change in length and sequence in
      Alzheimer's disease, and possibly in other dementias.

PMID- 14660070
TI  - Executive personality traits and eating behavior.
AB  - Eating disorders, such as anorexia, bulimia, and binge eating disorder, commonly
      involve a dysregulation of behavior (e.g., a lack or excess of inhibition and
      impulsive eating patterns) that is suggestive of prefrontal dysfunction.
      Functional neuro-imaging studies show that prefrontal-subcortical systems play a
      role in eating behavior and appetite in healthy individuals, and that people with
      eating disorders have altered activity in these systems. Eating behavior is often
      disturbed by illnesses and injuries that impinge upon prefrontal-subcortical
      systems. This study examined relationships between executive functioning and
      eating behavior in healthy individuals using validated behavioral rating scales
      (Frontal Systems Behavior Scale and Eating Inventory). Correlations demonstrated
      that increased dysexecutive traits were associated with disinhibited eating and
      greater food cravings. There was also a positive association with cognitive
      restraint of eating, suggesting that increased compensatory behaviors follow
      disinhibited eating. These psychometric findings reinforce those of other
      methodologies, supporting a role for prefrontal systems in eating.

PMID- 14660071
TI  - Neurobehavioral correlates of impulsivity: evidence of prefrontal involvement.
AB  - Impulsivity is associated with the functioning of prefrontal-subcortical circuits
      particularly, the orbitofrontal circuit, which is shown in neuro-imaging studies
      of neurological and psychological disorders. Objective behavioral measures, such
      as go/no-go, antisaccades, and delayed alternation, have demonstrated sensitivity
      to prefrontal function. This study examined the relationship between
      orbitofrontal-sensitive measures and impulsivity in healthy adults, as measured
      by the Barratt Impulsiveness Scale-11 (BIS). Go/no-go and antisaccades correlated
      positively and delayed alternations correlated negatively with BIS subscales,
      even after controlling for demographic influences. The results add to the
      validity of the BIS and support a role for prefrontal cortex in impulse control.

PMID- 14660072
TI  - Brief clinical study: Lipid peroxidation and antioxidant status in children with
      acute purulent meningitis and encephalitis.
AB  - In this study, lipid peroxidation and antioxidant status were investigated in
      children with acute bacterial meningitis and encephalitis. The aim was to
      determine whether there was a possible role of free radicals in meningitis and
      encephalitis in childhood. Our study included 16 children with acute bacterial
      meningitis, 13 with encephalitis, and 17 control  subjects. Serum malondialdehyde
      (MDA), reduced glutathione (GSH), vitamin C, vitamin E, beta-carotene, and
      retinol levels were studied in all subjects within 6 h of admission. There was a
      statistically significant difference for serum MDA, GSH, and vitamin C between
      the groups. Serum MDA and vitamin C levels were higher, and serum GSH levels were
      lower in the study groups compared to the control group. Vitamin C levels were
      similar in both the encephalitis and control groups, but they were significantly
      lower in the children with encephalitis than the meningitis group. In conclusion,
      our study showed that serum MDA and GSH levels were affected in children with
      both meningitis and encephalitis, but vitamin C level was affected only in
      children with meningitis. Serum vitamin E, beta-carotene, and retinol levels were
      not changed in childhood meningitis and encephalitis.

PMID- 14660074
TI  - Increased calcium influx through acetylcholine receptors in dunce neurons.
AB  - Calcium homeostasis was studied in dunce, a Drosophila mutant that is defective
      in learning and memory. Fura 2-AM fluorescence photometry was used to measure the
      intracellular calcium concentration in wild type and dunce cleavage-arrested
      neurons under resting conditions and in response to neurotransmitters. After
      acetylcholine application, the peak [Ca2+]i was greater in dunce (693 +/- 125 nM)
      than in wild type neurons (464 +/- 154 nM), but half decay time was shorter in
      dunce (66 +/- 15 s) than in wild type neurons (104 +/- 40 s). In contrast, the
      application of glutamate, NMDA, dopamine, and serotonin had no effect on [Ca2+]i.
      These results indicate that calcium influx through acetylcholine receptors is
      increased in dunce, compared to wild type neurons. The results also suggest that
      calcium extrusion to the outside and/or calcium buffering are enhanced in dunce,
      compared to wild type neurons. This disturbance in the homeostasis of cytosolic
      calcium concentration in dunce may be implicated in defective associative
      learning in Drosophila, and may play a role in acute and chronic
      neurodegenerative disorders in the mammalian brain.

PMID- 14660078
TI  - Why we need arteriogenesis research.

PMID- 14660076
TI  - Auditory information processing is altered in novelty stress conditions: first
      session effects in auditory-evoked potentials.
AB  - Novelty conditions may elicit stress responses. First session effects are
      systematic changes in physiological parameters, resulting from the interference
      of physiological processes with novelty stress. Along with endocrinological
      changes, these stress responses may be accompanied by alterations of sensory and
      attentional processes. The present study examines the impact of novelty
      conditions on event-related potential indicators of auditory information
      processing and on cortisol. Twenty-two healthy subjects participated in a series
      of experimental sessions. Auditory-evoked potentials were recorded, and the
      plasma cortisol levels were determined. The first session causes an activation of
      the hypothalamo-hypopituitary-adrenal axis. The auditory-evoked potentials show
      an additional slow negative potential component in the novelty condition. This
      potential component is maximal at fronto-central electrode sites and reaches its
      peak at about 240 ms after stimulus onset. Similarities with the processing
      negativity suggest alterations in attention-related auditory information
      processing in the novelty condition encountered in the first session.

PMID- 14660079
TI  - Hemodynamic forces as a stimulus for arteriogenesis.
AB  - Ischemic heart diseases put a heavy economical burden on Western society. They
      remain one of the major causes of morbidity, and preventive or postoperative
      treatments are lengthy and expensive. In some patients of ischemic heart
      diseases, there is not a direct correlation between the degree of occlusion of
      major arteries and the development of medical symptoms or damage to the heart
      function. Interestingly, these patients develop well-formed collateral vessels
      that compensate for the decrease in blood supply to the heart wall. Clearly, the
      ability to understand why and how these patients develop collateral vessels may
      serve as a base for a new strategy to treat ischemic heart diseases by promoting
      collateral formation. The current article summarizes recent advances in the
      understanding of how collateral vessels develop and offers the authors' point of
      view on the central role of biomechanical forces in this process and the
      molecular mechanisms that underline it.

PMID- 14660080
TI  - Arteriogenesis: role of nitric oxide.
AB  - Arteriogenesis is an important process for adapting the pre-existing circuit of
      vessels into functional collateral conduits for delivery of oxygen enriched blood
      to tissue distal to occlusion of a large, peripheral conduit artery. Recent
      evidence has shown that arteriogenesis is regulated by nitric oxide (NO),
      angiogenic factors and shear stress. NO significantly impacts vasomotor tone to
      enhance conductance of the newly recruited collateral arteries, and this effect
      is augmented by exercise training prior to arterial occlusion. NO-mediated
      increases in vascular conductance allows for greater collateral dependent blood
      flow to the tissue distal to occlusion. NO production is also critical to the
      efficacy of therapeutic arteriogenesis achieved by delivery of exogenous
      angiogenic growth factors (VEGF, FGF-2) or by exercise training. The critical
      role of NO in therapeutic arteriogenesis is independent of NO-mediated changes in
      vascular conductance and implies a central role in arteriogenic signaling events.
      Maintenance, or improvement, of NO production and signaling, such as with regular
      exercise, may improve endothelial cell function and thus may help preserve the
      arteriogenic potential of preexisting collateral networks.

PMID- 14660081
TI  - Arteriogenesis: lessons learned from clinical trials.
AB  - Arteriogenesis is a naturally occurring process leading to formation of the true
      bypass collaterals capable of providing normal blood flow to the distal vascular
      bed. Promoting the development of such conductance blood vessels appears to be
      the most attractive therapeutic strategy in occlusive atherosclerotic disease.
      Although our understanding of molecular events regulating the blood vessel
      formation in adult organs is far from complete, there is a body of knowledge that
      allowed for planning and conduction of the early phase I and II clinical trials
      of therapeutic angiogenesis. Substantial human safety data, as well as important
      considerations of the growth factor formulation, delivery and duration of action
      have emerged from these trials. The current review focuses on lessons learned
      from double-blind, randomized Phase II trials of arteriogenesis.

PMID- 14660082
TI  - Arteriogenesis in peripheral arterial disease.
AB  - Lower extremity peripheral arterial disease (PAD) most frequently presents with
      lower limb pain on walking--intermittent claudication. As the disease progresses
      the patient might suffer from rest pain and/or ischemic ulceration--critical limb
      ischemia (CLI). The management of patients with PAD consists of life-style
      modifications and pharmacotherapy addressing the risk factors to minimize the
      risk for disease progression and mortality in myocardial infarction and stroke.
      Symptomatic invasive treatment consists of surgical or endovascular
      revascularization. Unfortunately, about 20-30% of patients with CLI can not be
      treated by any of these methods and the only option for them is often amputation.
      For this group of patients there is a great need for alternative treatment
      strategies and several strategies are currently tested to stimulate collateral
      artery growth (arteriogenesis). Arteriogenesis is defined as growth of
      preexisting arteriolar connections into true collateral arteries. It relies on a
      complex combination of increased shear stress, different growth factors,
      cytokines, proteolytic enzymes and initial local inflammation. It is probable
      that this process is important for disease progression and the pathophysiology of
      leg ischemia, but its impact needs to be further elucidated. Such efforts will
      also benefit attempts to stimulate arteriogenesis as therapy for leg ischemia.
      This article briefly discusses the basic mechanisms underlying arteriogenesis,
      and speculates how this knowledge influences our view of the pathophysiology and
      treatment of PAD, particularly lower limb ischemia.

PMID- 14660083
TI  - Tissue macrophages: "satellite cells" for growing collateral vessels? A
      hypothesis.
AB  - It has been demonstrated in several studies that collateral growth is associated
      with accumulation of macrophages around proliferating vessel. Macrophages are
      known to secrete vascular growth factors and metalloproteinases. Both are
      necessary for the development of a proper vasculature. Recent studies suggest
      that certain subpopulations of macrophages are also capable of
      transdifferentiating into vascular cells. There are good reasons to assume that
      shear force rises dramatically in preexisting arteriolar shunts after occlusion
      of the main supplying vessel. Based upon these two findings it was hypothesized
      that high shear forces lead to homing of circulating monocytes to the growing
      collateral artery. The majority of studies, however, indicate that monocytes home
      under low shear force conditions. Our own observations in monocyte depleted
      animals suggest that proliferation and transdifferentiation of tissue macrophages
      occurs locally in growing collateral vessels and is independent of circulating
      cells. We thus propose that local proliferation and transdifferentiation of
      tissue macrophages rather than homing of circulating monocytes play a major role
      in arteriogenesis.

PMID- 14660084
TI  - Inhibition of collateral artery growth by mibefradil: possible role of volume
      regulated chloride channels.
AB  - Endothelial cell swelling is one of the earliest hallmarks of arteriogenesis, the
      growth and maturation of collaterals. Mibefradil was found to block endothelial
      Cl(-) channels that control the volume of endothelial cells. Thus the authors
      investigated whether the blockade of volume-controlling endothelial cell channels
      would translate into an inhibition of arteriogenesis. In BALB/c mice, the right
      femoral artery was ligated and the animals received either mibefradil or solvent
      (phosphate-buffered saline [PBS]) via osmotic minipumps. Laser Doppler perfusion
      ratio (R/L) of ligated versus nonligated distal hindlimb increased from 0.06 +/-
      0.01 (immediately after ligation) to 0.25 +/- 0.02 (day 7) in the PBS group and
      only from 0.07 +/- 0.02 to 0.13 +/- 0.02 in the mibefradil group (p <.01).
      Collateral artery diameters were significantly smaller in the mibefradil group
      (61 +/- 4.7 microm) versus controls (77.3 +/- 0.9 microm) (p <.05). Relative
      hemoglobin oxygen saturation measurements confirmed these findings (p <.02). The
      inhibition of arteriogenesis in the mibefradil group suggests that endothelial
      Cl(-) channels are involved in the initiation of arteriogenesis.

PMID- 14660085
TI  - Vascular endothelial growth factor response in porcine coronary and peripheral
      arteries using nonsurgical occlusion model, local delivery, and liposome-mediated
      gene transfer.
AB  - Angiogenesis and arteriogenesis play an important role in advanced vascular
      occlusive diseases. Whether angiogenesis or arteriogenesis predominate depends on
      the preexisting collateral vessel network, the type and location of occlusion,
      and different developmental origin of the arteries. Angiogenesis and
      arteriogenesis were investigated following vascular endothelial growth factor
      (VEGF) treatment in different arteries important in occlusive arterial diseases
      using a newly developed porcine arterial occlusion model. Porcine coronary and
      peripheral arteries were occluded interventionally using blinded stent grafts.
      Gene transfer was performed using a needle injection catheter and cationic lipid
      DOCSPER as gene carrier. DNA and gene expression in arterial tissue was examined
      using polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR. Vessel
      development was determined by angiography, immunohistochemistry, and measurement
      of capillary density. The transfected gene and its expression were found 3 months
      following application. In tissue adjacent to coronary arteries, there was
      significantly enhanced capillary density but no increase in angiographic score.
      In contrast, tissue surrounding peripheral arteries demonstrated no enhancement
      of capillary density but an enhancement in angiographic score. These results
      demonstrate differential responses to VEGF treatment in coronary and peripheral
      arteries resulting predominantly in either angiogenesis or arteriogenesis.
      Further investigation of VEGF signaling pathway is necessary for better
      understanding of the processes of vascular development, which may have potential
      impact on the design of cardiovascular therapeutics.

PMID- 14660086
TI  - Therapeutic angiogenesis/arteriogenesis in the chronic ischemic rabbit hindlimb:
      effect of venous basic fibroblast growth factor retroinfusion.
AB  - Therapeutic induction of angiogenesis has been shown in experimental hindlimb
      ischemia. An alternative to targeting the ischemic hindlimb tissue via the
      severely stenosed or occluded artery consists in the intact venous system, e.g.,
      by retroinfusion. We tested whether basic fibroblast growth factor (bFGF)
      enhances angiogenesis induction. Therefore, we applied bFGF retrogradely as
      compared to intramuscular application. Furthermore, we assessed whether bFGF
      induced angiogenesis was enhanced by low-dose VEGF coapplication. Chronic
      hindlimb ischemia in rabbits was established by excision of the femoral artery at
      day 0 (d0). At d7, baseline collateral number in the ischemic limb and collateral
      flow velocity of contrast agent (frame count score) were assessed. Thereafter,
      saline solution (control group) or bFGF (20 microg/kg) with or without VEGF (10
      microg/kg) was retroinfused through the femoral vein. Alternatively, bFGF (20
      microg/kg) was injected into thigh and calf muscles. At d35, collateral growth
      and flow velocity were quantified, and tissue samples were analyzed for capillary
      density. In the untreated control group, capillary/muscle fiber (C/FM) ratio of
      the ischemic limb was 0.87 +/- 0.12, and collateral number as well as frame count
      score at -d35 did not change compared to d7 (107% +/- 7% and 109% +/- 10% of
      baseline, respectively). Retrograde application of bFGF induced capillary and
      collateral growth (C/FM ratio 1.56 +/- 0.19 and frame count 161% +/- 29% of
      baseline), resulting in enhanced flow velocity (143% +/- 13%), similar to the
      intramuscular application of bFGF. Additional low-dose VEGF retroinfusion did not
      further increase capillary/collateral growth (1.49 +/- 0.08 and 172% +/- 26%) nor
      perfusion velocity (149% +/- 7%). The authors conclude that bFGF retroinfusion is
      a feasible approach of inducing angiogenesis and arteriogenesis in an ischemic
      hindlimb, resulting in increased blood perfusion, which was not further extended
      by additional low-dose VEGF coapplication.

PMID- 14660087
TI  - Identification of a cis-element regulating transcriptional activity in response
      to fluid shear stress in bovine aortic endothelial cells.
AB  - Fluid shear stress exerts numerous effects on gene expression in endothelial
      cells. To investigate the regulatory mechanisms involved, we designed
      oligonucleotides composed of a 20-bp core containing the classical shear stress
      response element (SSRE+) or of a 20-bp core, in which base pairs flanking the
      SSRE were mutated (SSRE-). Hexamers of the oligonucleotides were cloned in front
      of reporter genes, transfected in bovine aortic endothelial cells (BAECs), and
      subjected to either a continuous low shear stress (3 dynes cm(-2)) or to a
      stepwise increase in shear stress from 3 dynes cm(-2) to 12 dynes cm(-2) (16/4
      h). Shear stress increased reporter gene activity in cells transfected with pSSRE
      , but not with pSSRE+. Cyclic strain (6%, 1 Hz, 4 h) did not significantly affect
      reporter gene activity. In gel retardation assays, more proteins bound to SSRE-
      than to SSRE+ in response to high shear stress. In competition experiments, a
      cAMP response element-binding (CREB) protein-specific oligonucleotide suppressed
      protein binding to the SSRE-; however, an antibody directed against CREB itself
      did not affect protein binding to the SSRE+. Our results indicate that the
      sequence ACC(G)/(T)AGACCAG represents a novel SSRE and that a protein that binds
      a CREB-specific oligonucleotide is part of the complex implicated in response to
      shear stress.

PMID- 14660088
TI  - Biopanning of single-chain antibodies expressing phages reveals distinct
      expression patterns of angiogenic and arteriogenic vessels.
AB  - "Therapeutic angiogenesis" requires targeted delivery of growth factors for
      maximal benefit and limitation of potential hazards such as enhancement of tumor
      or plaque angiogenesis. Physiological distinctions between angiogenesis and
      collateral growth suggest the possibility of targeting selectively collateral
      endothelium. This article describes the generation of collateral-targeting single
      chain antibodies (scFv). Membrane preparations of growing collateral arteries
      from rats were used to produce collateral-targeting antibodies (CTAs) via
      immunization of mice. ScFv were generated from CTA-producing hybridoma and cloned
      into the pV gene of M13 phages. Phages expressing collateral-targeting scFv (CT
      scFv) were selected via repeated exposure to activated collateral arteries
      followed by reamplification. CT scFv could specifically be amplified, selected,
      and sequenced. Phages expressing CT scFv bound selectively to proliferating
      collateral vessels as identified by positive Polycyclic Nuclear Antigen (PCNA)
      staining and homed specifically to collateral endothelium after in vivo injection
      but bound neither to control vessels nor to tumor vessels. This study reveals
      major differences between angiogenic and collateral endothelium and delivers a
      tool that will allow the stimulation of collateral growth without promoting tumor
      or plaque angiogenesis.

PMID- 14660090
TI  - X-ray diffraction of the molecular substructure of human articular cartilage.
AB  - The molecular substructure of human articular cartilage has been difficult to
      study because of its complex composition and high degree of hydration. Using
      newly available small-angle X-ray diffraction (SAX) instrumentation that allows
      very short exposure times (0.1 to 10 sec), we have obtained spatially resolved
      information concerning the disposition of collagen fibers in the matrix of
      cartilage from the normal and osteoarthritic ankle and knee joints of human
      cadavers. Surprisingly, in zones of cartilage damage, such as in
      preosteoarthritic lesions or in the severely degenerated cartilage of
      osteoarthritic joints, collagen fibers of the deeper layers tended to be
      reoriented from the vertical. The SAX technique represents a nondestructive
      method of analyzing the collagen network in cartilage. Taken together, the data
      suggest a rigid control mechanism for the fiber network and an extensive passive
      reorganization of the collagen fiber orientation in diseased joint cartilage.

PMID- 14660091
TI  - Subcutaneous tissue mechanical behavior is linear and viscoelastic under uniaxial
      tension.
AB  - Subcutaneous tissue is part of a bodywide network of "loose" connective tissue
      including interstitial connective tissues separating muscles and surrounding all
      nerves and blood vessels. Despite its ubiquitous presence in the body and its
      potential importance in a variety of therapies utilizing mechanical stretch, as
      well as normal movement and exercise, very little is known about loose connective
      tissue's biomechanical behavior. This study aimed to determine elastic and
      viscoelastic mechanical properties of ex-vivo rat subcutaneous tissue in uniaxial
      tension with incremental stress relaxation experiments. The elastic response of
      the tissue was linear, with instantaneous and equilibrium tensile moduli of 4.77
      kPa and 2.75 kPa, respectively. Using a 5 parameter Maxwell solid model, material
      parameters micro(1) = 0.95 +/- 0.24 Ns/m and micro(2) = 8.49 +/- 2.42 Ns/m
      defined coefficients of viscosity related to time constants tau(1M) = 3.83 +/-
      0.15 sec and tau(2M) = 30.15 +/- 3.16 sec, respectively. Using a continuous
      relaxation function, parameters C = 0.25 +/- 0.12, tau(1C) = 1.86 +/- 0.34 sec,
      and tau(2C) = 110.40 +/- 25.59 sec defined the magnitude and frequency limits of
      the relaxation spectrum. This study provides baseline information for the stress
      strain behaviors of subcutaneous connective tissue. Our results underscore the
      differences in mechanical behaviors between loose and high-load bearing
      connective tissues and suggest that loose connective tissues may function to
      transmit mechanical signals to and from the abundant fibroblasts, immune,
      vascular, and neural cells present within these tissues.

PMID- 14660092
TI  - Ultrastructural determinants of murine achilles tendon strength during healing.
AB  - The mechanisms by which tendon strength is established during growth and
      development and restored following injury are not completely understood and are
      likely to be complex, multifactorial processes. Several studies examining the
      relationship between mechanical behavior and ultrastructural characteristics of
      tendons and ligaments during growth and maturation suggest that collagen fibril
      diameter is strongly correlated with tendon strength. Because of the similarities
      between development and repair processes of musculoskeletal tissues, increases in
      tendon strength during healing may be related to increases in fibril
      ultrastructural parameters such as fibril size, numerical density, and area
      fraction. In this study, we compared murine Achilles tendons at various time
      points after tenotomy with sham-operated controls in tensile tests to failure and
      examined tendons using electron microscopy to assess collagen fibril
      ultrastructure. We found that in the 6-week period following Achilles tenotomy,
      fibril mean diameter remained significantly smaller than sham-side diameter by a
      factor of 2-3. Despite the persistently small fibril size, increasing numerical
      density resulted in a gradual increase in fibril area fraction. Biomechanical
      strength did not reach that of intact tendons until some time between 5 and 7
      weeks, approximately the same time period when fibril area fraction began to
      approach sham values. These data suggest that parameters other than collagen
      fibril size are most responsible for increased tendon strength during healing.

PMID- 14660093
TI  - N-telopeptide of type II collagen interacts with annexin V on human chondrocytes.
AB  - Type II collagen binds to chondrocytes through integrins and annexin V. While the
      potential integrin binding sites have been identified, it is unclear which
      domains bind to annexin V. Proteolytic fragments of collagen are known to
      modulate cell signaling pathways resulting in degradation of articular cartilage;
      it is unknown whether annexin V binds to the fragments. The focus of our study
      was to determine the binding of type II collagen and its fragments to
      chondrocytes using flow cytometry and fluorescence microscopy. The N-telopeptide
      binds to annexin V, whereas the C-telopeptide and triple helical peptides do not.
      These data suggest that the binding of the N-telopeptide of type II collagen is
      through annexin V, whereas binding of the C-telopeptide and the triple helical
      peptide to the surface of chondrocytes are potentially facilitated through other
      collagen receptors, such as integrins or cell-associated matrix proteins.

PMID- 14660094
TI  - Editorial: Genitourinary pathology 120 years on.

PMID- 14660095
TI  - Transition zone carcinoma of the prostate gland: a common indolent tumour type
      that occasionally manifests aggressive behaviour.
AB  - AIMS: Tumours arising in the transition zone (TZ) of the prostate gland are often
      well differentiated and considered clinically unimportant. We have observed
      examples of high-grade TZ cancers that prompted this study. METHODS: Review of
      654 radical prostatectomy specimens previously assessed by systematic whole organ
      histology identified 187 (29%) TZ cancers of which 76 (11.6%) represented the
      index (main) tumour. These were compared with a volume-matched group of 76
      peripheral zone (PZ) carcinomas. RESULTS: Fifty-nine of 76 TZ index carcinomas
      had additional minor tumours mainly located in the PZ. Compared to PZ tumours of
      similar size, TZ tumours had significantly lower Gleason scores, less Gleason
      grade 4/5 and lower rates of capsular penetration and positive surgical margins.
      However, within this TZ tumour group, seven carcinomas had a major Gleason grade
      4 or 5 component with high rates of capsular penetration (57%) and positive
      surgical margins (43%). Positive anterior and bladder neck margins were more
      common in TZ carcinoma than peripheral tumours and transperineal biopsy was the
      method of choice for TZ cancer diagnosis. CONCLUSIONS: A subset of TZ carcinoma
      characterised by high tumour grade has a significant risk of extraprostatic
      spread, margin positivity and possible biochemical failure. We recommend
      transperineal prostate biopsy for TZ tumour diagnosis and histological sampling
      of the anterior TZ at radical prostatectomy, even if macroscopically normal, to
      detect patients at risk from aggressive TZ carcinoma.

PMID- 14660096
TI  - The reporting of prostate cancer on needle biopsy: prognostic and therapeutic
      implications and the utility of diagnostic markers.
AB  - Prostate needle biopsy remains the gold standard for diagnosing prostate cancer.
      Prostate cancer on needle biopsy can be evaluated by numerous techniques of
      quantifying tumour extent, Gleason score, and the presence of perineural invasion
      (PNI). These modalities can help clinicians in assessing the risk of
      extraprostatic disease, progression likelihood, and in helping men with prostate
      cancer choose among therapeutic options. This review details the information that
      should be included in the routine pathology report. Recent advances in molecular
      biology of prostate carcinogenesis have identified many molecular markers for
      prostate cancer. While several are extremely promising as diagnostic
      immunohistochemical markers, other prognostic markers are not yet ready to be
      used in routine practice until they are validated by large prospective studies.

PMID- 14660097
TI  - Assessment of ethnic variation in serum levels of total, complexed and free
      prostate specific antigen. Comparison of Maori, Pacific Island and New Zealand
      European populations.
AB  - AIMS: To determine whether age-adjusted levels of serum total (tPSA) and
      complexed (cPSA) prostate specific antigen and the ratio of free to tPSA (%fPSA)
      differ by ethnic group independent of symptomatic disease. METHODS: The serum
      levels of tPSA, cPSA, and %fPSA in relation to age, ethnicity and obstructive
      urinary symptoms were examined in 1405 Maori, Pacific Island and New Zealand
      European men in the Wellington region of New Zealand, and indicative reference
      range estimates produced. Participants were non-randomly selected from two study
      populations. RESULTS: tPSA and cPSA increased with age while %fPSA decreased with
      age in all ethnic groups. Maori showed higher tPSA values in the 60-69 age group
      than other ethnic groups. cPSA increased more rapidly with age in Maori than in
      New Zealand Europeans or Pacific Islanders. %fPSA differed according to age
      across all three ethnic groups. The median and 5th percentile Pacific Island
      %fPSA values were higher in comparison to the %fPSA reference ranges of all other
      ethnic groups and were also higher than those reported in other studies. Once
      adjusted for urinary symptom score, only %fPSA in Pacific Island subjects
      remained significantly higher than that in New Zealand Europeans (P<0.001).
      CONCLUSIONS: Our study indicates that %fPSA differs by ethnicity independent of
      symptomatic prostate disease.

PMID- 14660098
TI  - Stage pT1 bladder carcinoma: diagnostic criteria, pitfalls and prognostic
      significance.
AB  - Recognition of early invasion (stage pT1) in urothelial neoplasia is one of the
      most challenging areas in bladder pathology, and reproducibility between
      pathologists is a major issue. This fact, together with the proposal by some
      urologists to treat early invasive tumours more aggressively, makes the accurate
      detection of pT1 lesions even more relevant in clinical practice. In recent
      years, the morphologic features and patterns of invasion of tumour into the
      lamina propria have been more accurately characterised and standardised, and
      although some of the features are subtle, they can be of great utility in the
      accurate assessment of pT1 staging. Histologic grade, changes at the stroma
      epithelial interface, the characteristics of the invading epithelium, and the
      stroma-associated response are among the most important clues for appropriate pT1
      staging and these are discussed in this review. Common problems in stage pT1
      disease evaluation include, tangential sectioning--due to an inability to orient
      transurethral resection specimens--crush and cautery artefacts, and a streaking
      inflammatory infiltrate. With few exceptions, the criteria discussed in this
      review allow pathologists to separate superficial bladder tumours consistently
      and reproducibly into non-invasive (pTa) tumours and tumours that have invaded
      the lamina propria (pT1), the latter having a significantly poorer prognosis.
      This review is intended to assist the surgical pathologist by presenting
      appropriate diagnostic criteria, by describing common pitfalls and by outlining
      the different histologic patterns of invasion of urothelial carcinoma into the
      lamina propria. The value of pT1 tumour substaging, as a predictor of bladder
      cancer progression is also discussed.

PMID- 14660099
TI  - Distinctive neoplasms characterised by specific chromosomal translocations
      comprise a significant proportion of paediatric renal cell carcinomas.

PMID- 14660100
TI  - Mucinous tubular and spindle cell carcinoma and post-neuroblastoma carcinoma:
      newly recognised entities in the renal cell carcinoma family.

PMID- 14660101
TI  - Renal pathology in the tuberous sclerosis complex.

PMID- 14660102
TI  - Quantification of G250 mRNA expression in renal epithelial neoplasms by real-time
      reverse transcription-PCR of dissected tissue from paraffin sections.
AB  - AIM: Renal cell carcinoma (RCC) represents the most common malignant tumour in
      the kidney and is resistant to conventional therapies. G250 is a tumour
      associated antigen and is expressed mainly in clear cell RCC. It is a potential
      therapeutic target as well as a diagnostic marker for RCC. Previous studies
      relating to G250 protein or G250 mRNA expression in RCC using human tissue have
      largely been limited to immunohistochemical or conventional RT-PCR approaches
      that lack reproducibility, are subject to observer bias and are at most semi
      quantitative. In this study, we evaluated the feasibility of using real-time RT
      PCR in quantifying G250 mRNA expression using tissue dissected from paraffin
      sections of renal epithelial neoplasms. Using this approach, we performed a
      preliminary study investigating the relationship between G250 expression and
      tumor behavior in clear cell RCC. METHODS: A total of 53 radical nephrectomy
      specimens with renal epithelial neoplasms (nine oncocytoma, seven chromophobe
      RCC, four papillary RCC and 33 clear cell RCC) were included in this study. SYBR
      Green real-time RT-PCR was performed using the ABI PRISM 7700 Sequence Detection
      System. A TATA box-binding protein (TBP) was used as an endogenous reference
      gene. RESULTS: Our study showed that real-time RT-PCR is a reliable approach in
      quantifying G250 mRNA expression using paraffin sections. Using this methodology,
      G250 mRNA was detected in all of the clear cell RCCs, but none of the other types
      of tumours studied or in normal kidney tissue. Our study also suggested that the
      expression of G250 mRNA might correlate with tumour stage and overall survival.
      CONCLUSION: Among common renal epithelial neoplasms, G250 is a specific marker
      for clear cell RCC. Quantification of G250 mRNA expression by real-time RT-PCR
      using paraffin sections is a feasible approach for future clinical studies in
      evaluating the prognostic and predictive value of G250 in clear cell RCC.

PMID- 14660103
TI  - Renal dysplasia produced by obstructive uropathy in the fetal lamb.
AB  - AIM: This study was undertaken to investigate the renal changes associated with
      obstruction of the urinary tract in the fetal lamb early in gestation (50 days).
      It was also undertaken to determine if urinary tract obstruction proximal or
      distal to the urinary bladder would result in varying renal morphology. METHODS:
      Timed-gestation ewes at 50-days gestation were anaesthetised, and the lambs
      exposed. Males had their urethra and urachus ligated with a fine silastic tubing.
      Females had one ureter ligated with the same tubing. They were delivered at term
      and sacrificed. The kidneys were weighed, measured and processed for histological
      examination. RESULTS: Three lambs (2 males and 1 female) survived. All 5 kidneys
      were small (2.2+/-0.4g, normal 17.3+/-1.3g), and had lost their normal
      architecture. Microscopically, these kidneys had few glomeruli, a relative
      abundance of stroma with apparent nodular collections of tubules surrounded in
      some instances by a cuff of fibrous stromal tissue. CONCLUSION: The morphologic
      features produced by urinary tract obstruction at 50-days gestation in the lamb
      resembled those normally associated with human cystic renal dysplasia. The site
      of the obstruction had no effect on the development of subsequent renal
      pathology.

PMID- 14660104
TI  - Test and teach. Diagnosis: Benign metaplastic papillary change in an endometrial
      polyp.

PMID- 14660106
TI  - A clinicopathological study of three cases of severe acute respiratory syndrome
      (SARS).
AB  - AIMS: The severe acute respiratory syndrome (SARS) caused a large outbreak of
      atypical pneumonia in Beijing, China from early March 2003. We report the
      pathological features from three patients who died of SARS. METHODS: Autopsies
      were performed on three patients who died 9-15 days after the onset of the
      illness, and the clinical and laboratory features reviewed. Tissue sections were
      stained with haematoxylin and eosin (H&E), and in situ reverse transcriptase
      polymerase chain reaction (RT-PCR) on lung sections was performed using SARS
      coronavirus-specific primers. RESULTS: The typical gross pathological change in
      the lungs was diffuse haemorrhage on the lung surface. Histopathological
      examination revealed serous, fibrinous and haemorrhagic inflammation in most
      pulmonary alveoli, with capillary engorgement and some capillary microthrombosis.
      The pulmonary alveoli were thickened with interstitial mononuclear inflammatory
      infiltrates, diffuse alveolar damage, desquamation of pneumocytes and hyaline
      membrane formation; fibrinoid material and erythrocytes were present in alveolar
      spaces. There were thromboemboli in some bronchial arterioles. Haemorrhagic
      necrosis and reduced numbers of lymphocytes were observed in lymph nodes and
      spleen. In situ RT-PCR detected SARS coronavirus RNA in type II alveolar cells,
      interstitial cells and bronchiolar epithelial cells from all three patients.
      CONCLUSIONS: Severe immunological damage in lung tissue is responsible for the
      clinical features of SARS.

PMID- 14660107
TI  - Uterine malignant mixed mullerian tumour with pilomatrixoma-like areas.

PMID- 14660108
TI  - Pseudocystic leiomyoma of the ovary: a case report and literature review.

PMID- 14660109
TI  - Intra-aortic balloon pump related thrombosis of the abdominal aorta resulting in
      visceral ischaemia.

PMID- 14660110
TI  - Needle aspiration cytodiagnosis of mucinous (colloid) carcinoma of male breast.

PMID- 14660111
TI  - Outcomes of glandular cytopredictions.

PMID- 14660114
TI  - A study of environmental tobacco smoke in South Australian pubs, clubs and cafes.
AB  - Exposure to Environmental Tobacco Smoke (ETS) in hotels and clubs is of community
      concern and may lead to a variety of adverse health outcomes for workers and
      patrons. This study sought to measure ETS in both smoking and non-smoking areas
      of hospitality venues in South Australia and to assess the effectiveness of ETS
      control measures. Seven hotels, clubs and cafes were investigated and the
      concentrations of airborne nicotine and particulate matter (PM(10)) were measured
      as markers of ETS exposure during normal to busy periods. Overall average
      concentrations were higher in smoking areas (nicotine = 15 microg/m(3) and PM(10)
      = 255microg/m(3)) compared with non-smoking dining areas (nicotine = 7
      microg/m(3) and PM(10) = 192 microg/m(3)). The data demonstrate an approximate
      two-fold reduction of ETS within non-smoking areas and suggest that mechanical
      ventilation is only partially effective in preventing propagation of ETS
      throughout premises. Risk models suggest that ETS exposures in non-smoking areas
      may still represent an appreciable health risk. It is recommended that smoking be
      totally banned in enclosed publicly accessible areas.

PMID- 14660115
TI  - Linkages between biodiversity loss and human health: a global indicator analysis.
AB  - The association between health and biodiversity loss was explored by means of
      regression analysis on a global scale, with control for confounding by socio
      economic developments. For this we selected indicators of human health (life
      expectancy, disability adjusted life expectancy, infant mortality rate and
      percentage low-birthweight babies), biodiversity (percentage threatened species,
      current forest as a percentage of original forest, percentage of land highly
      disturbed by man) and socio-economic development (health expenditure as
      percentage of GNP, percentage one-year olds immunized, illiteracy rate, GNP per
      capita and development grade) on a country level. After controlling for relevant
      socio-economic confounders, both current forest as a percentage of original
      forest and the percentage of land highly disturbed by human activities had no
      relationship with one of the health indicators. The logarithm of the percentage
      threatened species, showed a positive association with life expectancy and
      disability adjusted life expectancy. The present study was not able to provide
      any empirical proof of a negative association between loss of biodiversity and
      human health at the global scale. This does not mean, however, that no such
      relationship exists, because there may be several reasons for our findings, like
      possible non-linearity of the relationship, lack of suitable indicators, non
      randomness in the sample of countries and the limitations of regression analysis
      in proving causality.

PMID- 14660117
TI  - Prevalence of Giardiasis due to wastewater reuse for agriculture in the suburbs
      of Asmara City, Eritrea.
AB  - A study was undertaken to assess the health impact of utilization of the raw
      domestic sewage for vegetable cultivation in the suburbs of the capital city of
      Asmara, Eritrea. Standard techniques were adopted for the analysis of the
      samples. Results showed heavy contamination of vegetables by faecal coliforms as
      well as with Giardia cysts. Stool samples of 75 farmers who were occupationally
      exposed revealed that 45% of them were harbouring giardia cysts. The dietary
      intake of raw salads (lettuce, cabbage) grown on the raw sewage appear to be a
      causative factor of Giardiasis in the farming community as well as in the town of
      Tsadachristian located on the suburbs of the capital city of Asmara. The hospital
      data of the affected town is compared with other towns of Eritrea. The result
      indicates agriculture reuse of untreated wastewater is a major cause for the
      increase in Giardasis.

PMID- 14660116
TI  - How clean is clean enough? Recent developments in response to threats posed by
      chemical and biological warfare agents.
AB  - Recent terrorist events underscore the urgent need to develop a comprehensive set
      of health-protective cleanup standards and effective decontamination technologies
      for use in the restoration of civilian facilities. Accurate scientific
      information remains limited in the area of biological warfare agents. However,
      new guidelines and calculated cleanup values are emerging for initial re-entry
      and long-term reoccupation following use of chemical warfare agents. This article
      addresses airborne, soil, and surface exposures following release of G-type
      chemical warfare agents and VX. Cleanup goals should be tailored to the type of
      population that may be exposed, potential exposure times, and other scenario
      specific considerations. Three different airborne concentrations are proposed for
      cleanup of public sector facilities. One value is recommended for initial re
      entry; a more conservative value is recommended for long-term monitoring and
      increased public confidence; and a third, even more conservative concentration
      represents essentially a no-effect level for round-the-clock airborne exposure.
      Health-based cleanup levels are provided for contaminated residential and
      industrial soil. Results are presented on the outcome of a preliminary risk
      assessment to determine safe surface levels (e.g., walls, floors, and handrails)
      for cleanup after exposure to the G agents and VX. Because specific cleanup
      criteria for most biological warfare agents remain problematic, recommendations
      are made for filling the knowledge gaps.

PMID- 14660118
TI  - Using qualitative psychology to investigate HACCP implementation barriers.
AB  - Hazard Analysis Critical Control Point (HACCP) is a system of food safety
      management that in the last few decades has become an increasing part of national
      government and international strategy to reduce the prevalence of food borne
      disease. Yet despite wide dissemination and scientific support of its principles,
      successful HACCP implementation has been limited. There has been very little in
      depth consideration of the reasons behind this, and qualitative psychological
      research examining the interplay of factors involved is almost non-existent. For
      this study therefore, four in-depth narrative interviews were carried out with
      small business owners attempting to implement HACCP. Non-prescriptive analysis of
      their interviews was carried out, and this revealed five key themes acting as
      'barriers' to successful implementation. These were of HACCP as difficult,
      burdensome and unnecessary, and hindered by staff and external problems. The
      analysis showed furthermore the complexity of issues underpinning problems with
      HACCP implementation and the way in which they operate at knowledge, attitude and
      behavioural levels. From this, essential issues to be addressed in order for
      successful HACCP to be achieved are put forward.

PMID- 14660119
TI  - Urban pollution and nickel concentration in serum.
AB  - The study's objective has been to evaluate whether urban pollution, here nickel
      compounds and metallic nickel (Ni) are present, could determine serum
      concentrations of the above mentioned metal. Out of a population of 394 Municipal
      Police employees, subjects with main confounding factors were eliminated. The
      remaining subjects were made comparable for sex, age, and length of employment.
      Thus, 160 subjects were included in the study: 80 traffic policemen (42 men and
      38 women) with outdoor activity exposed to urban pollutants in a direct way, and
      80 administrative workers (42 men and 38 women) with indoor unexposed activity.
      The results obtained in the studied population demonstrate that in traffic
      policemen the serum levels of Ni are more elevated than those in administrative
      workers; both in male and female workers. The authors hypothesise that the
      presence of Ni as fuel additive in lead free fuels and as catalyser in catalytic
      exhausts, which have been obligatory in Italy in new cars for the last 10 years,
      could be one of the causes for the increased serum levels of the above mentioned
      metal in traffic policemen.

PMID- 14660120
TI  - Investigation of the level of safety and appropriateness of playgrounds in Elazig
      city in Turkey.
AB  - This study was conducted to identify and evaluate the degree of appropriateness
      of children's playground standards and the level of compliance with the current
      safety specifications of the playgrounds in Elazig city in Turkey. This was
      accomplished by on-site observation and measurement in the total of 24
      playgrounds present in this city centre. It was determined that 83.3% of the
      playgrounds were next to a street and in 60% of these playgrounds there were no
      fences or any barrier to keep children from running into the street. In 87.5% of
      playgrounds the surfacing was not in proper depth and good order. Separate
      playgrounds for different ages were provided in only 12.5% of the playgrounds. In
      62.5% of the playgrounds children were supervised to make sure they were safe.
      There was unsafe equipment in 95.8% of the playgrounds. In 83.3% of the
      playgrounds there were sharp edges, pinch points, or playground debris that might
      injure a child. The findings of the present study indicate that nearly all of the
      playgrounds in Elazig city center do not meet the criteria for playground
      standards and are not in compliance with the current safety specifications and
      need improvement.

PMID- 14660121
TI  - Composition of eye cosmetics (kohls) used in Cairo.
AB  - A total of 18 kohl samples were analysed using X-ray powder diffraction (XRPD)
      and scanning electron microscopy (SEM). All the samples were purchased in Cairo
      and eleven of them originated in Egypt. The main component of six samples was
      found to be galena (PbS); where four of these samples originated in Egypt and two
      in India. For a further ten samples the main component was found to be one of the
      following: amorphous carbon, calcite (CaCO(3)), cuprite (Cu(2)O), goethite
      (FeO(OH)), elemental silicon or talc (Mg(3)Si(4)O(10)(OH)(2)). For the last two
      samples the main component of each was an unknown amorphous organic compound.

PMID- 14660122
TI  - Migrant labour, racism and the British National Health Service.
AB  - This study explores the dynamics of racism, specifically its generation and
      reproduction as an ideology, and its role in affecting the reception and
      occupational location of migrant medical labour in Britain. It is argued that the
      treatment of 'overseas doctors' in Britain draws on a complex interplay between
      racism and nationalism underpinned by the historical construction of 'welfarism'
      as a moral legitimator of 'Britishness'. Through an exploration of internal and
      external immigration controls introduced with the aim of regulating migrant
      labour, we demonstrate how British social policy and elite discourses of 'race'
      combine to construct moral prescriptions of threat such that migrants and British
      born 'non-whites' entering the British medical profession are forced to negotiate
      'saviour/pariah' ascriptions indicative of discriminatory but contradictory
      processes specific to the operation of the British National Health Service as a
      normative institution.

PMID- 14660123
TI  - Psychosocial working conditions and self-reported long-term illness: a population
      based study of Swedish-born and foreign-born employed persons.
AB  - BACKGROUND: Knowledge pertaining to the relationship between migration status and
      psychosocial job characteristics and long-term illness is not readily available
      in the international literature. The aim of this study is to analyse the cross
      sectional associations between high psychological job demands and low decision
      latitude (high job strain), work-related social support and long-term illness
      among foreign-born and Swedish-born people. METHODS: The present study combines
      four annual simple random samples covering 1994-97 from the Swedish Annual Level
      of Living Survey (SALLS). A sub-sample, including only employed persons and
      consisting of 10,072 Swedish-born persons, 710 labour migrants and 333 refugees
      aged 25-64 years, was analysed using logistic regression. RESULTS: Refugees had a
      higher risk (OR=1.33; 95% CI: 1.05-1.69) of long-term illness than Swedes.
      Moreover, those experiencing both high job demands and a low decision latitude
      ran an increased risk (OR=1.74; 95% CI: 1.42-2.13) of long-term illness. About
      63% of the refugees among the unskilled/skilled manual workers had low decision
      latitudes in comparison with 17% of the intermediate and senior salaried
      employees. There were only small differences in job demands between labour
      immigrants, refugees and Swedes. There was no interaction between migration
      status and high job strain. However, refugees with low social support had nearly
      twice as high a risk of long-term illness as Swedes with high-level work-related
      social support. CONCLUSIONS: Refugees ran a higher risk of long-term illness than
      Swedes. Although there were no differences in risk between labour immigrants,
      refugees and Swedes under job strain, refugees with low work-related social
      support had a high risk of long-term illness. Unskilled/skilled refugee workers
      had lower decision latitudes than Swedes.

PMID- 14660124
TI  - Correlates of smoking behavior among Muslim Arab-American adolescents.
AB  - OBJECTIVES: Although ethnic and gender differences in adolescent smoking have
      been well documented, factors influencing susceptibility to smoking and
      experimentation among the ethnic group of Muslim Arab-American youth have
      received little research attention. This study examines the smoking prevalence,
      the associations of known smoking risk factors, religious and cultural influences
      with adolescents' susceptibility to smoking and experimentation with cigarettes
      among the ethnic group of Muslim Arab-American adolescents, in an Islamic Academy
      in Fairfax County, Virginia. DESIGN: Cross-sectional survey data collected
      confidentially from a sample of 480, 7th to 12th grade students in Fairfax
      County, Virginia, during the 1998-99 school year. Outcome measures included self
      reported susceptibility to smoking and smoking behavior. RESULTS: The overall
      prevalence of susceptibility to smoking, experimentation (ever smoking), 30 day
      and current smoking was 50%, 45%, 18% and 12%, respectively. Almost twice as many
      males as females were susceptible to smoking and reported to have experimented
      with cigarettes. Peers smoking was the most significant risk factor associated
      with both susceptibility and experimentation for both genders (OR=3.0, 95% CI=1.8
      4.5; OR=3.0; 95% CI=1.8-4.6, respectively), while perceived peer norms were a
      risk factor for ever smoking but not for susceptibility to smoking. Religious
      influence and perceived negative consequences of smoking were protective against
      ever smoking for both genders (OR=0.7, 95% CI=0.5-0.9; OR=0.8, 95% CI=0.7-0.9,
      respectively). Culturally based gender-specific norms were significantly
      associated with increased risk of susceptibility to smoking for males only (OR=3,
      95% CI=1.3-7), while religious influence was protective against susceptibility to
      smoking for females only (OR=0.6, 95% CI=0.4-0.8). CONCLUSION: Social influences
      based smoking prevention programs may be effective for adolescents from Muslim
      Arab cultures; however, they should be modified to address culturally based
      gender norms and may benefit from the incorporation of Islamic messages
      denouncing smoking behavior.

PMID- 14660126
TI  - Knowledge and beliefs regarding type 2 diabetes mellitus in rural Mexico.
AB  - OBJECTIVE: To investigate adults with Type 2 diabetes mellitus (DM) in a rural
      area of Mexico in order to explore their knowledge and beliefs regarding
      diabetes. DESIGN: A pilot study was conducted in a rural town in Morelos, Mexico.
      Adults over the age of 40 were invited to participate in a screening program for
      DM, and those who had been previously diagnosed with Type 2 DM were invited for
      an interview to learn about their knowledge and beliefs regarding diabetes.
      RESULTS: The glucose screening project enrolled 521 participants, including 56
      previously diagnosed with Type 2 DM. Interviews were conducted with 37 of those
      with previously diagnosed DM. Almost all individuals in the interview sample held
      causal explanations based on non-scientific beliefs. Home remedies were used by a
      majority, and most informants used one or more methods. Blood glucose monitoring
      was virtually non-existent. The most frequently reported source of social support
      was family members. Physicians appeared to be a less important source of support.
      CONCLUSION: Most respondents would like to improve management of their DM, and
      they try to do so with whatever resources they can afford; however, a lack of
      information and restricted economic resources appear to limit the availability of
      modern medical resources. Without the availability of glucose
      monitoring/screening programs and affordable medication, it appears unlikely that
      improved treatment of Type 2 DM will occur. Dietary changes and other management
      approaches may be best modified through family and community influence, instead
      of the individual lifestyle modification strategies described in the US Type 2 DM
      management model.

PMID- 14660125
TI  - Knowledge, attitudes and behaviours of caregivers regarding children's exposure
      to environmental tobacco smoke among Arabic and Vietnamese-speaking communities
      in Sydney, Australia.
AB  - OBJECTIVE: The aim of this study was to inform the design of a culturally
      appropriate health communication campaign addressing exposure of young children
      to Environmental Tobacco Smoke (ETS) in homes and cars, targeted at caregivers of
      children aged 0-6 years in the Arabic and Vietnamese-speaking communities in
      Sydney, Australia. DESIGN: Nine focus groups (five Arabic and four Vietnamese)
      were conducted by qualified bilingual facilitators, recorded, transcribed, then
      translated and analysed qualitatively. RESULTS: Results revealed concerning
      levels of knowledge, attitudes and behaviours regarding children's exposure to
      ETS. A poor understanding existed regarding what constituted passive smoking and
      the severity and extent of harm that ETS has on children. Smoking attitudes and
      behaviours described were not always consistent with the concern expressed about
      children's vulnerability to smoke. Initial changes in smoking patterns at home
      since the arrival of children were not always sustained. Despite awareness of the
      harm caused by smoking in the presence of their children, some caregivers
      continued to smoke in closed environments. Others felt it was sufficient
      protection to smoke in another room, with doors and/or windows open or by
      ensuring that visible smoke did not reach the child directly, whilst some smoked
      in the home or car only when children were not present. Smoking attitudes and
      behaviours in the presence of children were influenced by cultural and social
      norms associated with smoking. The desire to be sociable and hospitable often
      superseded concerns for children's health. CONCLUSION: The findings suggest that
      an effective communication campaign focusing on ETS and children in the Arabic
      and Vietnamese-speaking communities in Sydney should attempt to address knowledge
      deficits regarding ETS, as well as tackling entrenched culturally related
      attitudes and behaviours associated with smoking which are strongly linked to
      sociability and hospitality.

PMID- 14660127
TI  - Developing a global perspective on drug information systems.

PMID- 14660128
TI  - Development of a structured generic drug intervention model for public health
      purposes: a brief application of motivational interviewing with young people.
AB  - Brief applications of Motivational Interviewing (MI) emerged around 15 years ago
      to target problematic alcohol and other drug use. Interventions which
      specifically target illicit drug use, young people, or which are delivered in
      settings other than health-care services have, however, been relatively slow to
      develop. The needs of young people for interventions distinct from those offered
      to adults are considered, as a precursor to an outline of the structure of a
      newly adapted intervention targeting drug use in general among young people.
      Based upon earlier topic-based approaches developed by Rollnick et al. this
      intervention is innovative in simultaneously targeting a range of drugs in
      pursuit of secondary prevention objectives, while also seeking to manifest the
      spirit of MI. The intervention consists of a single-session face-to-face
      conversation of up to 60 minutes duration. Data are presented which describe the
      development and conduct of this intervention during the course of an efficacy
      trial, with promising efficacy data themselves reported elsewhere. Observations
      are made on intervention delivery and consideration is given to implications for
      further novel targeting of young people and within the field of addiction
      interventions more generally. [McCambridge J, Strang J. Development of a
      structured generic drug intervention model for public health purposes: a brief
      application of motivational interviewing with young people.

PMID- 14660129
TI  - Substance use and the prediction of young offender recidivism.
AB  - The problem considered is whether self-reported substance use can be used in the
      estimation of recidivism risk among youths placed in secure care. The Secure Care
      Psychosocial Screening (SECAPS) and offending records of 447 youths admitted to
      detention centres in South Australia were examined. The target outcome was any
      new offending within 6 months of release. Use of a psychoactive substance at the
      time of committing the most recent offence was not a significant predictor of
      subsequent offending, nor was acknowledging having a problem with drug or alcohol
      use. In relation to the recent use of alcohol, marijuana, hallucinogens,
      sedatives/hypnotics, narcotics, stimulants and inhalants, only the use of alcohol
      and inhalants appeared to have significant relationships with recidivism. While
      the relationships were too small to permit using these items on their own to
      estimate re-offending risk, recent alcohol and inhalant use could be included as
      part of a broader recidivism risk assessment. [Putnins AL. Substance use and the
      prediction of young offender recidivism.

PMID- 14660130
TI  - Health and well-being outcomes for drug-dependent offenders on the NSW Drug Court
      programme.
AB  - Given the centrality of drug treatment to the drug court framework, the
      proliferation of drug courts in the United States, and their emergence more
      recently in Australia, it is surprising that such little attention has been given
      to assessing their therapeutic effect. This evaluation aimed to assess the health
      and well-being of drug-dependent offenders diverted to the New South Wales Drug
      Court, and monitor changes in their health and well-being throughout 12 months of
      programme participation. The study consisted of baseline interviews with 202
      offenders accepted into the programme between February 1999 and April 2000, and
      follow-up interview at 4, 8 and 12 months with participants who remained on the
      programme. Health and well-being was assessed at each follow-up using the Short
      Form-36 Health Survey (SF-36) the OTI social functioning scale, and self-reported
      spending as a proxy for illicit drug use. The health of male Drug Court
      participants prior to commencing the programme was significantly poorer than
      Australian population norms. The results provided evidence of significant and
      sustained improvements in health and well-being for the 51 participants who
      competed each follow-up interview. Furthermore, significant improvements were
      found for offenders who remained on the programme for at least 4 months but less
      than 12 months. However, the positive health outcomes are limited by the low
      programme retention rate. These results indicate that significant health outcomes
      can be achieved for at least some heavily drug-dependent, recidivist offenders
      through the drug court model. [Freeman K. Health and well-being outcomes for drug
      dependent offenders on the NSW Drug Court programme.

PMID- 14660131
TI  - General practitioners' diagnostic skills and referral practices in managing
      patients with drug and alcohol-related health problems: implications for medical
      training and education programmes.
AB  - The aim of this study was to determine the current practices of established
      general practitioners in managing patients with drug and alcohol-related problems
      and identify gaps in training. A random sample of general practitioners completed
      a survey assessing diagnostic skills and referral practices concerning alcohol
      and illicit drug use in general practices in February 1999, comprising 110
      general practitioners registered with the Central Sydney Division of General
      Practice. The main outcome measures were competent skills and knowledge,
      willingness to treat. The majority (96%) of GPs provided clinically appropriate
      responses for at least one drug category, although none received this rating for
      all six. Most general practitioners reported that they were unwilling to treat
      heroin and cocaine problems themselves but expressed willingness to refer
      patients appropriately. More than a quarter of general practitioners were unaware
      of the safe drinking levels for men and women or the appropriate treatment for
      patients consuming above such levels. Age, years in practice, type of practice,
      willingness to obtain drug use histories and post-graduate training were all
      significantly associated with general practitioners' willingness to treat and
      competence in managing drug and alcohol-related problems. In this study, general
      practioners reported low levels of skills and referrals for treatment of illicit
      drug use and suboptimal skills in the management of alcohol problems. The results
      suggest that a more comprehensive approach to education and training is required
      to bring about a change in practice behaviour. [Fucito LM, Gomes BS, Murnion B,
      Haber PS. General practitioners' diagnostic skills and referral practices in
      managing patients with drug and alcohol-related health problems: implications for
      medical training and education programmes.

PMID- 14660132
TI  - Antagonist-precipitated heroin withdrawal under anaesthetic prior to maintenance
      naltrexone treatment: determinants of withdrawal severity.
AB  - This study sought to characterize antagonist-precipitated heroin withdrawal
      during and immediately following anaesthesia and to identify the determinants of
      withdrawal severity and duration in 48 dependent heroin users. Objective
      withdrawal signs decreased significantly with each naloxone bolus administered
      under anaesthetic. The cost (amount) of the final heroin administration and the
      number of hours between last heroin use and commencement of anaesthesia were
      significant, independent predictors of the severity of withdrawal symptomatology.
      While 83% (40/48) of participants completed withdrawal according to objective
      criteria and commenced maintenance naltrexone treatment, almost half (22/48) were
      unable to commence naltrexone on the day of the procedure due to residual
      withdrawal signs. Fourteen of these 22 participants subsequently commenced
      naltrexone (median number of days between admission and commencement of
      naltrexone was 2, range 1 - 6) while eight left treatment prior to initiation of
      naltrexone. Significantly fewer of those with more severe withdrawal signs during
      anaesthesia commenced naltrexone (40% vs. 60%). While the severity and duration
      of withdrawal symptomatology may be moderated by encouraging participants to
      reduce (or cease) heroin use close to the time of withdrawal, for a substantial
      proportion of participants in this study, heroin withdrawal by this antagonist
      precipitated procedure was neither rapid nor painless. [Ali R, Thomas P, White J,
      McGregor C, Danz,C, Gowing L, Stegink A, Athanasos P. Antagonist-precipitated
      heroin withdrawal under anaesthetic prior to maintenance naltrexone treatment:
      determinants of withdrawal severity.

PMID- 14660133
TI  - Emergency management of inadvertent accelerated opiate withdrawal in dependent
      opiate users.
AB  - Six opiate-dependent drug users presented to the local emergency department
      within a 10-day period with symptoms of severe opioid withdrawal immediately
      following intravenous use of recently acquired street 'heroin'. The withdrawal
      picture was similar to that described in patients undergoing rapid opioid
      detoxification, suggesting that the substance injected was contaminated with an
      opiate antagonist. A number of potential compounds are discussed, including
      naltrexone and buprenorphine, and recommendations for the medical management of
      severe opiate withdrawal within an emergency setting are outlined. [Lubman DI,
      Koutsogiannis Z, Kronborg I. Emergency management of inadvertent accelerated
      opiate withdrawal in dependent opiate users.

PMID- 14660134
TI  - Smoking cessation interventions for in-patients: a selective review with
      recommendations for hospital-based health professionals.
AB  - A selective review of the literature was conducted to provide evidence-based
      recommendations for the clinical management of hospitalized smokers. The Cochrane
      library, in particular the Cochrane review of 'Interventions for smoking
      cessation in hospitalised patients', was the basis for the review and was
      supplemented with other clinical and non-clinical literature where the review did
      not inform clinicians sufficiently. Evidence was reviewed on issues considered by
      the authors to be of importance to health professionals interested in providing a
      smoking cessation intervention to their patients. The review suggests that
      effective hospital interventions: incorporate an in-patient intervention lasting
      greater than 20 minutes in duration with extended post discharge follow-up;
      consist of at least five intervention contacts; and be delivered over at least a
      3-month period. Furthermore, interventions should include in-patient advice and
      counselling, the provision of nicotine replacement therapy and extended proactive
      post discharge telephone support. The review also indicates that cessation
      interventions are particularly effective when delivered to patients with a
      cardiovascular diagnosis. All health professionals may be effective in providing
      cessation treatments; however, the addition of a specialist smoking cessation
      counsellor appears to improve interventions in this setting. Finally, without the
      development of supportive systems, routine intervention with smoking patients by
      health professionals is unlikely. Recommendations for the delivery of effective
      smoking cessation interventions in hospitals are provided. [Wolfenden L, Campbell
      E, Walsh RA, Wiggers J. Smoking cessation interventions for in-patients: a
      selective review with recommendations for hospital-based health professionals.

PMID- 14660135
TI  - Being stoned: a review of self-reported cannabis effects.
AB  - Although there has been considerable research into the adverse effects of
      cannabis, less attention has been directed toward subjective effects that may be
      associated with ongoing cannabis use. Examination of self-reported cannabis
      effects is an important issue in understanding the widespread use of cannabis.
      While reviews have identified euphoria as a primary factor in maintaining
      cannabis use, relaxation is the effect reported most commonly in naturalistic
      studies of cannabis users, irrespective of the method used. Self-reported effects
      in 12 naturalistic and 18 laboratory studies were compared. Regardless of
      methodology there was considerable variation in the effects experienced.
      Variation has been reported in terms of opposite effects being experienced by
      different individuals, variation of effects by individuals within a single
      occasion and between occasions of use. Factors that might explain this variation
      are outlined. Limitations of the available literature and suggested directions
      for future research are discussed. [Green B, Kavanagh D, Young R. Being stoned: a
      review of self-reported cannabis effects.

PMID- 14660136
TI  - Where to for tobacco regulation: time for new approaches?
AB  - From a public health perspective, tobacco remains the number one drug problem
      facing most countries, even countries such as Australia, which has made
      considerable headway in reducing tobacco use and associated harm. Clearly more
      needs to be done, but is it the case that more of the same will be sufficient? In
      this Harm Reduction Digest based in part on a presentation at the 'International
      Research Symposium Preventing Substance Use, Risky Use and Harm: What is Evidence
      Based Policy?' held in Fremantle, Western Australia in February 2003, the author
      proposes a new regulatory framework through which to further reduce tobacco
      related harm. The paper challenges whether the current profit motive is an
      appropriate driver of the tobacco industry and suggests a new model of tobacco
      regulation.

PMID- 14660137
TI  - Crushing buprenorphine tablets.

PMID- 14660139
TI  - Enabling households to support successful migration of AIDS orphans in southern
      Africa.
AB  - Most southern African orphans are cared for by extended families but the
      implications of the spatial dispersal of such families are seldom recognized:
      orphans often have to migrate to new homes and communities. This paper, based on
      qualitative research conducted with children and guardians in urban and rural
      Lesotho and Malawi, examines orphans' migration experiences in order to assess
      how successful migration might best be supported. Most children found migration
      traumatic in the short term, but over time many settled into new environments.
      Although much AIDS policy in southern Africa stresses the role of communities,
      the burden of care lay with extended family households. Failed migrations, which
      resulted in renewed migration and trauma, were attributable to one of two
      household-level causes: orphans feeling ill-treated in their new families or
      changes in guardians' circumstances. Policy interventions to reduce disruption
      and trauma for young AIDS migrants should aim at facilitating sustainable
      arrangements by enabling suitable households to provide care. Reducing the
      economic costs of caring for children, particularly school-related costs, would:
      allow children to stay with those relatives (e.g. grandparents) best able to meet
      their non-material needs; reduce resentment of foster children in impoverished
      households; and diminish the need for multiple migrations.

PMID- 14660140
TI  - Assessing the impact of orphanhood on Thai children affected by AIDS and their
      caregivers.
AB  - The implications of orphanhood for AIDS-affected children in Thailand is a
      subject which has received little scholarly attention despite the intensity and
      longevity of the epidemic in that country. The present study presents preliminary
      findings from a longitudinal investigation of the circumstances and welfare of
      Thai youth who have lost one or both parents to AIDS-related causes and the
      families who care for them. Based on interviews and focus groups carried out in
      Chiang Mai province in 2001-2002, the study finds that most of the children left
      orphaned by AIDS were being cared for by members of their extended family,
      especially grandparents or maternal aunts, and that many caregiving households
      were experiencing significant financial hardship which might have implications
      for the children's long-term well-being and stability and for their opportunities
      for educational advancement. Concern were also expressed about the unavailability
      or inaccessibility of childcare for AIDS-affected children and the perceived
      instability of fostering arrangements which placed young children in the care of
      elderly relatives.

PMID- 14660141
TI  - HIV incidence and risk behaviours after voluntary HIV counselling and testing
      (VCT) among adults aged 19-35 years living in peri-urban communities around
      Chiang Mai city in northern Thailand, 1999.
AB  - The Thai government began HIV voluntary counselling and testing (VCT) in all
      provinces in 1992. We evaluated HIV incidence after participants utilized VCT and
      its effect on risk behaviours among northern Thai adults aged 19-35 years. A
      total of 924 men and 1,327 women volunteered to participate in the study.
      Subjects were counseled, interviewed (socio-demographic, HIV risk behaviour, and
      HIV testing history), and tested for HIV infection at baseline and at 6 months
      follow-up. All participants were provided group pre-test counselling; HIV test
      results were provided in individual confidential post-test counselling. Overall,
      329 of 391 men and 621 of 669 women who reported a prior HIV test before
      participating in our study reported negative results at the previous test. Of
      these, nine men and 13 women tested positive at baseline, giving incidence rates
      of 1.04 and 0.69 per 100 person years (PY), respectively. Recent risk behaviour
      was rare; as a result, the effects of VCT on risk behaviours among the study
      participants could not be determined. The HIV incidence after VCT among this
      study population is substantial. Studies to investigate factors associated with
      HIV incidence among VCT clients could provide insights for more effective HIV
      prevention.

PMID- 14660142
TI  - Integrating prevention of mother-to-child HIV transmission into antenatal care:
      learning from the experiences of women in South Africa.
AB  - In 1999, for the first time in South Africa, a Mother-to-Child HIV Transmission
      (MTCT) prevention programme was implemented at the routine primary care level and
      not as part of a research protocol. A total of 264 women attending prenatal care
      in these clinics were interviewed in Xhosa using a standardized questionnaire.
      All had been offered HIV testing, and 95% had accepted. Women who had not been
      tested were four times more likely to believe that in the community families
      reject HIV-positive women (p<0.005). Of women who tested, 19% were HIV positive
      and 83% had told their partner that they had taken the test. HIV-positive women
      who had not disclosed testing to their partners were three times more likely to
      believe that, in the community, partners are violent towards HIV-positive women
      (p<0.005); 86% stated that they would have taken AZT if found to be HIV positive.
      Only 11% considered that the use of formula feeding indicated that a woman was
      HIV positive. In conclusion, routine prenatal HIV testing and interventions to
      reduce perinatal HIV transmission are acceptable to the majority of women in a
      South African urban township, despite an awareness of discrimination in the
      community towards HIV-positive women.

PMID- 14660143
TI  - Feasibility and acceptability of a specialist clinical service for HIV-infected
      mineworkers in South Africa.
AB  - Occupational settings offer an ideal opportunity to provide preventive health
      services for HIV-infected workers. A specialized clinic was established in a
      mining hospital in the Free State, South Africa, with the primary aim of
      delivering preventive therapy such as isoniazid to those at high risk of
      tuberculosis (individuals with HIV infection or silicosis), and cotrimoxazole to
      those at highest risk for opportunistic infections. The clinic design has taken
      regard of the importance of minimizing stigma, protecting confidentiality,
      monitoring potential side effects, supporting adherence and identification of
      prophylaxis failure. The clinic opened in April 1999 and, by August 2001, 1773
      patients had attended at least once; 1762 are HIV-infected and 11 have silicosis.
      Of those with HIV infection, most were asymptomatic at their first visit. The
      clinic has achieved high acceptability: 99% of persons who were actively
      recruited to the service agreed to attend. The number still attending after a
      median of 13 months from recruitment was 1,270 (72%) and only 48 (2.7%) have
      declined continued attendance. Most losses were due to termination of employment
      unrelated to a medical condition. The clinic has already been successfully
      replicated in two other regions of the mining health service in South Africa and
      provides a model for workplace HIV clinical services that could be used for
      implementation of further interventions such as antiretroviral therapy.

PMID- 14660144
TI  - Adolescent reproductive health and awareness of HIV among rural high school
      students, North Western Ethiopia.
AB  - Ethiopia is faced with an increasing problem from HIV infection, and the
      vulnerability of adolescents is a key concern. There is little information on the
      knowledge, attitudes and practices of this age group with respect to HIV,
      sexually transmitted diseases and preventive measures. We conducted a cross
      sectional study among 260 students from two rural high schools in North Western
      Ethiopia. We found that although the general awareness of HIV was high, correct
      knowledge of the virus and its modes of transmission was shown in only 44% of
      adolescent boys and 41% of adolescent girls. Knowledge of HIV and condoms was
      lower among students whose parents were farmers, significant so among girls
      (p=0.02). Use of condoms among sexually active single male students (49%) was
      insufficient but was higher than among adolescents in many other African
      settings. Knowledge of STDs was generally low: 82% of adolescent males and 37% of
      adolescent females had some awareness of STDs. Almost 20% of sexually active
      males in the study had previously experienced an STD, almost all of whom had
      visited a commercial sex worker. Targeted interventions are warranted among
      adolescents and sex workers in Ethiopia complemented by STD treatment services.

PMID- 14660145
TI  - Community sex education among adolescents in rural Uganda: utilizing indigenous
      institutions.
AB  - Although adolescent girls in Uganda are particularly vulnerable to HIV infection,
      providing relevant sexual health education to them is problematic. The senga
      (father's sister), is the traditional channel for socializing adolescent girls
      into sex and marriage among many ethnic groups in Uganda. This paper discusses
      the implementation and community acceptability of 'modern' sengas who were
      trained to provide HIV-related counselling to adolescent girls. Fourteen sengas
      were trained in two villages and, in the course of the 1-year study, 247
      individuals made a total of 403 visits to them. By including both traditional
      services (such as advice on and assistance with labial elongation) and modern
      health and sex education, the sengas provided a 'middle road' between tradition
      and modernity. As a result, despite initial suspicion by the community, their
      activities were supported by the community generally and effective as
      intervention.

PMID- 14660146
TI  - Measuring quality of life among HIV-infected women using a culturally adapted
      questionnaire in Rakai district, Uganda.
AB  - To examine self-reported quality of life and health status of HIV-infected women
      and a comparison sample of HIV-uninfected women in rural Uganda, we culturally
      adapted a Lugandan version of the Medical Outcomes Survey-HIV (MOS-HIV). We
      administered a cross-sectional survey among 803 women (239 HIV-positive and 564
      HIV-negative) enrolled in a community study to evaluate maternal and child health
      in Rakai District, Uganda. The interview took 20 minutes and was generally well
      accepted. Reliability coefficients were >0.70, except for role functioning,
      energy and cognitive function. MOS-HIV scores for HIV-positive women were
      correlated with increasing number of physical symptoms and higher HIV viral load.
      Compared to HIV-negative women, HIV-positive women reported lower scores than HIV
      negative women for general health perceptions, physical functioning, pain,
      energy, role functioning, social functioning, mental health and overall quality
      of life (p all <0.01). Substantial impairment was noted among women reporting
      >/=4 symptoms. In summary, HIV-positive women reported significantly poorer
      functioning and well-being than HIV-negative women. We conclude that patient
      reported measures of health status and related concepts may provide a feasible,
      reliable and valid method to assess the impact of HIV/AIDS and future therapeutic
      interventions to improve patient outcomes in rural Africa.

PMID- 14660147
TI  - Women from Africa living with HIV in London: a descriptive study.
AB  - There are no studies that have examined the particular needs and experiences of
      African women living with HIV in the UK at a time when they represent an
      increasingly large proportion of the UK HIV epidemic. This study explores the
      illness biographies and daily lives of HIV-positive African women receiving
      treatment in London. Sixty-two women from 11 African countries attending HIV
      specialist clinics in five London hospitals participated in self-completion
      questionnaires and in depth semi-structured interviews. Using a narrative
      approach, women were asked to talk about their HIV status in the broader context
      of their life history. Important differences exist within this group based mainly
      on nationality, income, education level and legal status in the UK. However,
      marked similarities also emerged which were related in part to their situation as
      migrants and were compounded by their illness. Stigma, both actual and perceived,
      had a profound impact on women's lives, making control of information about their
      situation a matter of acute concern. This had an effect on how women accessed
      health services and voluntary sector agencies. The resilience of women in dealing
      with difficulties in their lives was strengthened by religious belief. Such
      similarities and differences need to be properly understood by health and social
      care professionals if they are to offer the most appropriate care for this
      growing population of patients.

PMID- 14660148
TI  - Burden of infection among heads and non-head of rural households in Rakai,
      Uganda.
AB  - The objective was to determine HIV prevalence, symptomatology and mortality among
      adult heads and non-heads of households, in order to assess the burden of HIV on
      households. It was a community study of 11,536 adults aged 15-59, residing in
      4,962 households in 56 villages, Rakai district, Uganda. First, 4,962 heads and
      6,574 non-heads of households were identified from censuses. Interviews were then
      used to determine socio-demographic/behavioural characteristics. HIV
      seroprevalence was diagnosed by two EIAs with Western blot confirmation. The
      adjusted odds ratio (OR) and 95% confidence intervals (CI) of HIV infection in
      household heads and non-heads were estimated by multivariate logistic regression.
      Age-adjusted mortality was also assessed. HIV prevalence was 16.9% in the
      population, and 21.5% of households had at least one HIV-infected person
      (<0.0001). HIV prevalence was higher among heads than non-heads of households
      (21.5 and 13.3%, respectively, OR=1.79; CI 1.62-1.97). Most household heads were
      males (70.5%), and HIV prevalence was 17.8% among male heads compared with 6.6%
      in male non-heads of households (OR=2.31; CI 1.65-2.52). Women heading households
      were predominantly widowed, separated or divorced (64.4%). HIV prevalence was
      30.5% among female heads, compared with 15.6% in female non-household heads
      (OR=1.42; CI 1.15-1.63). Age-adjusted mortality was significantly lower among
      male household heads than non-heads, both for the HIV-positive (RR=0.68) and HIV
      negative men (RR=0.63). Among women, HIV-negative female household heads had
      significantly higher mortality than HIV-uninfected female non-heads (RR=1.72).
      HIV disproportionately affects heads of households, particularly males. Mortality
      due to AIDS is likely to increase the proportion of female-headed households, and
      adversely affect the welfare of domestic units.

PMID- 14660149
TI  - Intentions to use condoms in Rwandan secondary school students.
AB  - A survey was conducted among 474 (213 female and 261 male) students (mean age 21
      years) in three secondary schools in rural Rwanda in order to evaluate their
      attitudes towards condoms. Male students and those with sexual experience had
      more favourable attitudes towards condom utilisation than female students and
      those without prior sexual contacts. Of the 44% with reported sexual experience,
      reported age at first encounter was lower in boys (16.8 years) than in girls
      (18.3 years; p=0.03); 73 students (36%) reported regular use of condoms. Having
      more than one sexual partner was reported by 42 (9%), of whom 20 (48%) claimed
      regularly using a condom. Intention to use condoms was reported by 77% of the
      male and 53% of the female students (p=0.001). In addition, those with prior use
      of condoms and those having multiple partners were more likely to report future
      use intentions than others. Future campaigns in Rwanda should therefore focus on
      sensitising adolescents to a more positive attitude towards condoms and include
      modules to reduce condom misconceptions and stigma.

PMID- 14660150
TI  - How do Africans view the impact of HIV? A report from a Ugandan community.
AB  - Although much research has been conducted on the causes and outcomes of HIV, far
      less has been written about how the affected societies themselves perceive the
      epidemic. This is particularly true in sub-Saharan Africa. In this study we
      interviewed 50 residents (28 female, 22 male) from 30 villages across the Rakai
      and contiguous portion of the Masaka districts in southwest Uganda about the
      problems affecting their communities as a result of HIV. These problems formed
      three main categories: (1) lack of able-bodied adults, (2) lack of care for
      children, and (3) mental and social problems. The interrelatedness of these
      categories is discussed in the context of communities that are struggling to
      recover from the effects of HIV.

PMID- 14660152
TI  - Abuse and violence history of men and women in treatment for methamphetamine
      dependence.
AB  - The Methamphetamine Treatment Project offers the opportunity to examine the
      history of abuse and violence in a sample of 1016 methamphetamine users
      participating in a multisite study between 1999-2001. Reporting of abuse and
      violence was extensive, with 80% of women reporting abuse or violence from a
      partner. Men were more likely to report experiencing violence from friends and
      others. A high percentage of study participants reported a variety of threatening
      or coercive experiences with their partners. Past and current interpersonal
      violence is a characteristic of the lifestyles of the majority entering treatment
      for methamphetamine dependence.

PMID- 14660153
TI  - Predictive validity of the ASAM Patient Placement Criteria for naturalistically
      matched vs. mismatched alcoholism patients.
AB  - This study examined the predictive validity of the ASAM Patient Placement
      Criteria for matching alcoholism patients to recommended levels of care. A cohort
      of 248 patients newly admitted to inpatient rehabilitation, intensive outpatient,
      or regular outpatient care was evaluated using both a computerized algorithm and
      a clinical evaluation protocol to determine whether they were naturalistically
      matched or mismatched to care. Outcomes were assessed three months after intake.
      One common type of undertreatment (ie, receiving regular outpatient care when
      intensive outpatient care was recommended) predicted poorer drinking outcomes as
      compared with matched treatment, independent of actual level of care received.
      Overtreatment did not improve outcomes. There also was a trend for better
      outcomes with residential vs. intensive outpatient treatment, independent of
      matching. Results were robust for both methods of assessment. Corroboration by
      more research is needed, but the ASAM Criteria show promise for reducing both
      detrimental undertreatment and cost-inefficient overtreatment.

PMID- 14660154
TI  - Looking back on cocaine dependence: reasons for recovery.
AB  - Factors that contributed to long-term recovery from cocaine dependence were
      examined as part of a 5-year national follow-up study of 708 patients from 45
      treatment programs in eight U.S. cities. Outcomes from 33% of the sample were
      highly favorable at follow-up, including no drugs detected in urine or hair
      specimens, no self-reported use of any drugs, less than daily alcohol use, and no
      illegal activity or arrests during the past year. Major reasons cited for these
      improvements were motivations to change, positive influences of family, strength
      from religion and spirituality, and help from drug treatment. "Recovery" was
      viewed as a continuous process and one that benefits from lessons learned in
      treatment. These retrospective attributions affirm many of the same findings from
      prospective outcome studies and contribute to a conceptual framework for
      treatment process and recovery.

PMID- 14660155
TI  - Gender differences in individuals with comorbid alcohol dependence and post
      traumatic stress disorder.
AB  - This study investigated gender differences in a sample of outpatient, treatment
      seeking individuals (N=84) with comorbid alcohol dependence and post-traumatic
      stress disorder (PTSD). Assessments included substance use severity, trauma
      history, PTSD symptomatology, and comorbid psychiatric disorders. Men reported an
      earlier age of onset of alcohol dependence, greater alcohol use intensity and
      craving, and more severe legal problems due to alcohol use. Women reported
      greater exposure to sexually related traumas, greater frequency and intensity of
      avoidance of trauma-related thoughts and feelings, and greater social impairment
      due to PTSD. Women were more likely than men to demonstrate higher rates of other
      anxiety disorders and test positive for cocaine at treatment entry. PTSD more
      often preceded alcohol dependence in women than in men. The results illustrate a
      number of gender differences that may shed light on etiologic models of comorbid
      alcohol dependence and PTSD.

PMID- 14660156
TI  - A comparison of the patterns of drug use among patients with and without severe
      mental illness.
AB  - We compared the patterns of substance use among patients with severe mental
      illness (SMI) served by three community treatment teams, substance users with non
      severe mental illness (NSMI), and substance abusers without mental illness (no
      mental illness: NMI). There were highly significant differences in substance use
      patterns among the groups: among patients with SMI, the order of drug preference
      was alcohol, cocaine, cannabis, and then heroin; in the NMI group, it was
      cocaine, alcohol, heroin, and then cannabis; while in the NSMI group, it was
      alcohol, cocaine, heroin, and then cannabis. The data suggest that the choice of
      drugs by individuals with SMI may be determined by factors related to their
      illness, in addition to the price and availability of the particular drug.

PMID- 14660157
TI  - Relationship between platelet serotonin uptake sites and measures of impulsivity,
      aggression, and craving among African-American cocaine abusers.
AB  - We investigated whether platelet-tritiated paroxetine binding, a measure of
      serotonin uptake sites, and behavioral measures of impulsivity, aggression, and
      craving differed between cocaine-dependent subjects and controls and whether
      paroxetine binding was related to these behavioral measures. One hundred and five
      African-American cocaine-dependent outpatients and 44 African-American controls
      were studied. Tritiated paroxetine binding sites on platelets were assayed, and
      standardized assessments of impulsivity, aggression, and craving were performed.
      The Bmax values of paroxetine binding were significantly reduced among cocaine
      patients compared to controls. Cocaine patients showed significantly higher
      scores on certain measures of sensation seeking, impulsivity, and aggression as
      compared to controls. Furthermore, paroxetine binding showed a significant
      negative correlation with most measures of sensation seeking, impulsivity, and
      aggression--though not craving--among cocaine patients. Our findings indicate
      that densities of serotonin uptake sites may be reduced among cocaine abusers and
      related to impulsive-aggressive behavioral dimensions.

PMID- 14660158
TI  - The MICA Case Conference Program at Tewksbury Hospital, Mass.: an integrated
      treatment model.
AB  - This report describes the MICA (Mentally Ill Chemically Abusing) Program at the
      Tewksbury Hospital campus in Tewksbury, Massachusetts. Several campus facilities
      collaborate in the MICA Program. Through Expert Case Conferences, principles of
      integrated psychosocial treatment with dual diagnosis patients are demonstrated.
      An expert clinician focuses on the interplay between psychological pain,
      characterological traits, defenses, and the patient's drug of choice. Patients
      who have participated in the program have reported positive experiences. The
      staff reported that the program has resulted in facility improvement in
      assessment and treatment of complex dual diagnosis patients.

PMID- 14660162
TI  - Comparison of nitric oxide production motion characteristics of sperm after
      cryopreserved in three different preparations.
AB  - Three ml of semen collected from 20 volunteers were divided into three aliquots:
      a) semen cryopreserved for 48 hr then swim-up method; b) using swim-up method
      then cryopreserving for 48 h; and c) using 45%-90% two layers PureSperm to
      prepare sperm then cryopreserved for 48 h. Motility characteristics were
      evaluated before cryopreservation and after thawing. NO was measured using the
      chemiluminescence method after centrifugation. The recovery rate and motion
      parameters were the highest in the swim-up group. NO produced in the swim-up
      group was significantly lower than the PureSperm group, and the PureSperm group
      was lower than the semen treated with cryoprotectant group. Best semen quality
      was achieved due to the decreased NO production.

PMID- 14660159
TI  - Effects of illicit drug use on adherence to prescribed antiretroviral medication.
AB  - This exploratory analysis compared adherence to antiretroviral medication on days
      that illicit drugs were used and on matched abstinence days in twelve subjects
      who used MEMS caps during participation in a clinical trial. Adherence on drug
      use days was lower in seven subjects, higher in one, and the same in four. Three
      subjects maintained 100% adherence despite illicit substance use on studied days.
      Thus, in a subset of patients, the actions involved in procuring drugs and the
      acute effects of using them contribute to non-adherence on those specific drug
      use days, associated with substance abuse. (Am J Addict 2003;12:455-458)

PMID- 14660163
TI  - Inhibitory actions of lead on steroidogenesis in MA-10 mouse Leydig tumor cells.
AB  - The inhibitory actions of Pb on StAR protein expression and steroidogenic enzymes
      on steroidogenesis were analyzed by both linear and 2nd order polynomial models
      in MA-10 mouse Leydig tumor cells. Lead acetate, ranging from 10(-8) M to 10(-5)
      M, caused inhibitory effects on StAR protein expression and steroidogenic
      enzymes. The correlation coefficients R2 (linear vs. 2nd order polynomial) were
      0.93 vs. 0.96 for human chorionic gonadotropin-stimulated progesterone
      production, 0.38 vs. 0.79 for dibutyryl cAMP-stimulated progesterone production,
      0.03 vs. 0.99 for the expression of StAR protein, 0.6 vs. 0.92 for P450 side
      chain cleavage enzyme activity, and 0.52 vs. 0.96 for 3beta-hydroxysteroid
      dehydrogenase activity. Thus, 2nd order polynomial model showed higher
      correlation coefficients than the linear model for predicting inhibitory actions
      of Pb on StAR protein expression and the activities of steroidogenic enzymes
      after exposure of Pb on steroidogenesis in MA-10 cells.

PMID- 14660164
TI  - Effect of Bu-zhong-yi-qi-tang on seminal plasma cytokine levels in patients with
      idiopathic male infertility.
AB  - Twenty-two idiopathic infertile patients were treated with Oriental herbal
      medicine, Bu-zhong-yi-qi-tang (Hochu-ekki-to). Seminal plasma sFas level elevated
      significantly after herb administration. There was an inverse correlation between
      seminal plasma IL-6 level and sperm concentration before treatment. After the
      administration of herb seminal plasma, sFas levels significantly correlated with
      sperm concentration. Seminal plasma IL-8 level did not change. Certain kinds of
      cytokine in the seminal plasma might play some role in improving semen quality
      with treatment.

PMID- 14660165
TI  - Effect of lifestyle factors on infertility in men.
AB  - Environmental factors, changes in lifestyle and occupational exposures are
      responsible for declining human semen quality. We investigated the effects of
      history of surgery and lifestyle choices on infertility of 271 infertile men and
      251 healthy volunteers. The frequency of varicocelectomy was significantly higher
      in infertile men (2.9%) than in controls (0.4%; P < 0.05). Alcohol use was
      significantly more common in infertile men (92%) than in controls (80%; P <
      0.01). Satisfaction with sexual life was greater in controls (85%) than in
      infertile men (77%; P < 0.05). Other factors had no effect.

PMID- 14660166
TI  - Surgical vs. untreated cryptorchidism: effects on fertility.
AB  - Forty-four patients with history of cryptorchidism were studied: 15 untreated
      (group A); 14 treated by orchiopexy at age 4.5 +/- 1.4 years (group B), and 15
      with unilateral orchiectomy of undescended testis at 8.4 +/- 1.6 years (group C).
      Testicular volume, semen analysis, and LH and FSH were measured. Normal sperm
      counts were noted in 53%, 36% and 47% of patients in groups A, B and C,
      respectively. FSH and LH serum levels showed no differences between the groups.
      Testicular volume of the normal descended testes showed no differences between
      the three groups. Positive correlation was obtained between testicular
      volume/sperm concentration and negative correlation between gonadotropins/sperm
      concentration. The remaining testicular volume and gonadotropin serum values from
      adults with history of chryptorchidism who underwent orchiectomy were not
      different from those orchiopexied treated nor with untreated patients. The
      percentage of men with sperm count greater than 20 millions/mL was lower in the
      orchiopexied men compared to A and C groups. There seems to be different
      etiologic factors in our patients.

PMID- 14660167
TI  - Minilaparotomy radical retropubic prostatectomy for prostate cancer.
AB  - Radical prostatectomy is still the gold standard for treating patients with
      clinically localized cancer. A total of 33 consecutive patients underwent
      minilaparotomy radical prostatectomy by a single surgeon. The minilaparotomy
      radical retropubic prostatectomy was performed via an eight-centimeter lower
      midline incision and a Book Walter retractor for surgical assistance. Mean
      patient age was 65 years (range 47 to 74). Tumor stages were observed as 12.1% of
      total for T1c, 21.2% for T2a, 45.5% for T2b, 6% for T3a and 15.2% for T3b.
      Satisfactory continence was achieved in 80% of the patients. 85% of patients
      revealed a prostate-specific antigen at a serum concentration of less than 0.2
      ng/ml. Minilaparotomy radical retropubic prostatectomy compares favorably with
      standard radical retropubic prostatectomy.

PMID- 14660168
TI  - Programmed cell death and survival pathways in prostate cancer cells.
AB  - Programmed cell death, or apoptosis, is a series of morphologically and
      biochemically related processes. The extrinsic (death receptor mediated) and
      intrinsic (mitochondrial-mediated) apoptotic pathways can be triggered by
      physiological and pharmacological substances. However, other molecular events
      influence the sensitivity of prostate cancer cells to apoptotic stimuli, leading
      to marked variations in the responsiveness of prostate cancer cell lines to
      individual stimuli. Modulation of apoptotic responses by over expression of anti
      apoptotic proteins (NF-kappaB, IAPs and Bcl-2), or attenuation of pro-apoptotic
      proteins (PTEN and Bax) may be responsible for the variations in sensitivity of
      these cell lines to hormone and chemotherapy. The expression of anti- and pro
      apoptotic proteins in some of the widely used in vitro models of prostate cancer
      is reviewed.

PMID- 14660169
TI  - Effect of chronic low dose of methotrexate on cellular proliferation during
      spermatogenesis in rats.
AB  - This study was conducted to evaluate cellular proliferation of germinal and non
      germinal elements of seminiferous tubules following continuous Day 1 to Day 17
      exposure of methotrexate (12.5 microgram) in male rats. There was significant
      decrease in the diameter of seminiferous tubules (P < 0.10) followed by increase
      of interstitial space (P < 0.01). The size of various stages of primary,
      secondary spermatocytes, and spermatids was altered significantly compared to
      controls. Vacuolization/decondensation of "chromatin-mass" in spermatocytes
      changed from rounded to oval. The size of the Sertoli and Leydig cells were
      reduced significantly. Basement membrane at some places seems to be disrupted and
      thin in experimental testis. Methotrexate induced cytotoxicity on the
      proliferation of cellular contents of seminiferous tubules elucidating the
      mechanism of dose-dependent drug induced testicular damage during
      spermatogenesis.

PMID- 14660170
TI  - Sperm velocity in seminal plasma and the association with gender of offspring.
AB  - The gender of the offspring is determined by the fertilizing sperm. Previous
      gender studies were based on washed sperm, but not on sperm in seminal plasma.
      The objective was to correlate motility parameters assessed during semen analyses
      with the offspring gender. For comparison, fixed sperm head DNA quantitated by
      Hoechst 33342 fluorescence microscopy was also analyzed. Forty-six patients
      undergoing assisted reproduction procedures resulted in livebirth deliveries with
      either male or female-predominant offsprings. Sperm head fluorescence was weakly
      correlated to the gender in 61% of the cases. Sperm of patients with male
      offsprings had slower curvilinear (44.2 +/- 1.8 mean +/- SEM, versus, 49.9 +/-
      2.7 micro /sec) and slower average path velocities (32.4 +/- 1.2 versus 36.3 +/-
      1.7 micro /sec). Using cut-off values for the curvilinear (< 49 micro /sec) and
      average path (< 36 micro /sec) velocities of sperm swimming in seminal plasma,
      the two parameters predicted 75 and 68% of the male offspring births,
      respectively. The data suggest that sperm movement in seminal plasma is a marker
      for factors that skew the ratio of the X- to Y-sperm populations.

PMID- 14660171
TI  - Sperm apoptosis in nonpregnant luteal phase sera after in vitro fertilization as
      assessed by comparative genomic hybridization.
AB  - Toxicity in serum has been reported in cases of recurrent spontaneous abortions
      and endometriosis. The null hypothesis was that serum toxicity was not involved
      in failed pregnancies after in vitro fertilization procedures. The objective was
      to expose donor sperm to pregnant versus nonpregnant patient sera and analyze for
      sperm DNA damaging effects using a novel comparative genomic hybridization
      method. Luteal phase sera (N = 21 cases) were drawn one week after embryo
      transfer. Colloid-washed donor sperm were incubated (48 h, 37 degrees C, 5% CO2
      in air) in 0% or 50% sera. Single-stranded DNA (ssDNA) of control sperm were
      stained in Hoechst 33342 and hybridized to Sybr Gold-stained ssDNA of sera
      treated sperm. Image analyses were performed and fluorescent intensities
      analyzed. Nonpregnant patient sera (57% of cases) were associated with DNA
      fragmentation (64.4 +/- 8.8 pixels; mean +/- S.E.M.) when compared with pregnant
      patient sera (106.3 +/- 8.4 pixels). There were no differences in the sera of
      biochemical (108.2 +/- 15.3) versus clinical pregnancy cases (105.3 +/- 11.4).
      The results suggest that nonpregnant patient sera contained factor(s) that cause
      DNA fragmentation leading to pregnancy losses.

PMID- 14660172
TI  - Almokalant glucuronidation in human liver and kidney microsomes: evidence for the
      involvement of UGT1A9 and 2B7.
AB  - 1. Almokalant, a class III antiarrythmic drug, is metabolized to form isomeric
      glucuronides identified in human urine. Synthesis of the total glucuronide was
      studied in human liver and kidney microsomes. Recombinant UDP
      glucuronosyltransferases (UGTs) were screened for activity and kinetic analysis
      was performed to identify the isoform(s) responsible for the formation of
      almokalant glucuronide in man. 2. From a panel of recombinant isoforms used, both
      UGT1A9 and 2B7 catalysed the glucuronidation of almokalant. The Km values in both
      instances were similar with 1.06 mM for the 1A9 and 0.97 mM for the 2B7. Vmax for
      1A9 was fourfold higher than that measured for UGT2B7, 92 compared with 21 pmol
      min(-1) mg(-1), respectively, but UGT1A9 was expressed at approximately twofold
      higher level than the UGT2B7 in the recombinant cell lines. Therefore, the
      contribution of UGT2B7 to almokalant glucuronidation could be as significant as
      that of UGT1A9 in man. 3. Liver and kidney microsomes displayed similar Km values
      to the cloned expressed UGTs, with the liver and kidney microsomes at 1.68 and
      1.06 mM almost identical to the 1A9. 4. The results suggest a significant role
      for UGT1A9 and 2B7 in the catalysis of almokalant glucuronidation.

PMID- 14660173
TI  - Transcriptional regulation of cytochrome P4503A4 gene expression: effects of
      inherited mutations in the 5'-flanking region.
AB  - 1. Understanding the genetic basis of interindividual variability in drug
      disposition and response is a fundamental focus for rational and individualized
      drug treatment. Cytochrome P4503A4 (CYP3A4) has a central role in human drug
      metabolism and polymorphic variation has been reported in this gene. 2. This
      study reports the in vitro functional analysis of inherited mutations in the 5'
      flanking region of the CYP3A4 gene using reporter constructs in which the 1141 bp
      proximal promoter region from the mutant alleles was inserted between a single
      copy of the CYP3A4 300 bp core distal enhancer (XREM) sequence and the cDNA for
      human secretory alkaline phosphatase. 3. Reporter constructs were co-transfected
      with an hPXR expression vector into human liver and intestinal cells in culture
      and xenobiotic modulation of CYP3A4 promoter activity determined by
      chemiluminescent secretory alkaline phosphatase assay. DNA-protein interactions
      were next examined using electrophoretic mobility shift assays. 4. The results
      demonstrated that inherited mutations in the CYP3A4 gene proximal promoter region
      could cause significant up-regulation of in vitro transcriptional activation by
      CYP3A4 xenobiotic inducers. In addition, the magnitude of the effect appeared to
      be dependent on the cell type used in the functional assays, possibly due to the
      differing availability of specific intracellular transcription factors or their
      activating ligands.

PMID- 14660174
TI  - Pharmacokinetic analysis of factors determining elimination pathways for sulfate
      and glucuronide metabolites of xenobiotics II: Studies with isolated perfused rat
      liver.
AB  - 1. To elucidate the determining factors for elimination pathways of sulfate and
      glucuronide metabolites of xenobiotics, a single-pass perfusion of 4
      methylumbelliferone (4MU) or p-nitrophenol (pNP) was performed with an isolated
      rat liver preparation. 2. Without bovine serum albumin in the perfusion system,
      clearance calculated based on the unbound concentration in the liver clearly
      showed that the net efflux clearances (CLeff) of sulfates from the sinusoidal
      membrane were much higher than those of glucuronides and that the biliary
      excretion clearances (CLb) of glucuronides were approximately two times larger
      than those of sulfates. 3. The ratios of CLeff to CLb were much higher for
      sulfates than those for glucuronides. The bile-oriented elimination of
      glucuronides or sinusoidal efflux-oriented elimination of sulfates was observed
      even using the perfusate including 3% bovine serum albumin, but the sinusoidal
      efflux of sulfates was extensively enhanced by bovine serum albumin in the
      perfusate. The mechanisms behind this stimulatory effect remain to be elucidated.
      4. For both compounds, CLb of glucuronide was comparable with CLb of sulfate,
      meaning that CLb is not responsible for the biliary excretion of glucuronides at
      extensively higher rate than sulfates. 5. Higher concentration of glucuronides in
      the liver, partly caused by much lower CLeff of glucuronides than that of
      sulfates, is likely responsible for the bile-oriented excretion of glucuronides.
      The extensive sinusoidal efflux of sulfates, leading to the urine-oriented
      excretion, is attributed to the substantially higher CLeff than CLb. 6. In
      conclusion, the sinusoidal efflux is an important factor for determining
      elimination pathways of both sulfates and glucuronides, although further studies
      are needed to clarify the mechanisms of the sinusoidal efflux.

PMID- 14660176
TI  - Stereoselective hepatic disposition of a diastereomeric pair of alphavbeta3
      antagonists in rat.
AB  - 1. The study investigated mechanisms underlying the stereoselective hepatic
      disposition observed in rats of a zwitterionic diastereomeric pair ((3S)-3-[(3R
      or 3S)-2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]pyrrolidin-1
      yl]-3-quinolin-3-ylpropanoic acid) with different lipophilicities. 2. In a
      recirculating isolated rat liver system, the more hydrophilic diastereomer II
      possessed biliary clearance, CLb, and bile-to-liver concentration ratio higher
      (about 10-30-fold) than the lipophilic zwitterion I, whereas both I and II
      exhibited comparably high concentration ratios between liver and perfusate.
      Although MK-571, a known multidrug resistance protein (MRP) inhibitor,
      significantly inhibited the CLb of both compounds, it did not inhibit their
      canalicular transport, as evident by unchanged concentration ratios between bile
      and liver of either I or II. 3. Following an intravenous infusion of I or II to
      Sprague-Dawley rats, the biliary clearance calculated either based on plasma
      (CL(b,p)) or liver concentration (CL(b,l)), of II was much higher than that of I
      (about 5-50-fold). In rats lacking multidrug resistance protein 2 (Mrp2) (Eisai
      hyperbilirubinemic rat, EHBR), the biliary excretion rate and CL(b,p) of II were
      also higher than the corresponding values for I. However, both CL(b,p) or CL(b,l)
      of either I or II were not reduced in EHBR, as compared with control SD rats. 4.
      In the in vitro rat canalicular membrane vesicle study, I and II exhibited no
      differences in their inhibitory effect on the Mrp2 mediated ATP-dependent [3H]DNP
      SG initial uptake (no inhibition at 10 microM and only about 40% inhibition at
      100 microM). 5. Collectively, these results suggested that (1) the difference in
      the hepatic disposition between the two isomers was due primarily to the
      difference in their transport mechanism across the canalicular membrane and (2)
      Mrp2 did not play a major role in the observed differences in the biliary
      excretion of the diastereomers I and II in rats.

PMID- 14660175
TI  - Application of structure-metabolism relationships in the identification of a
      selective endothelin A antagonist, BMS-193884, with favourable pharmacokinetic
      properties.
AB  - 1. Based on binding affinity, 2'-amino-N-(3,4-dimethyl-5-isoxazolyl)-4'-(2
      methylpropyl)[1,1'-biphenyl]-2-sulfonamide (2) was identified as an initial lead
      in a programme to identify selective endothelin (ET) receptor antagonists.
      However, the compound was extensively metabolized in preclinical animal species
      and human in vitro systems due to oxidative biotransformation. 2. To optimize
      this structural class, the site of metabolism of 2 was determined. This allowed
      for focussed structure-activity and structure-metabolism studies aimed at finding
      more metabolically stable analogues that maintained potency. New analogues were
      screened for their ET binding characteristics and their stability in rat and
      human liver microsomes. 3. The use of the microsomal stability screen was tested
      by the determination of the pharmacokinetic parameters of select analogues. A
      good correlation was found between reduced rates of rat microsomal metabolism and
      reduced clearance in the rat. 4. N-(3,4-dimethyl-5-isoxazolyl)-4'-(2
      oxazolyl)[1,1'-biphenyl]-2-sulfonamide (3) was identified as an analogue with
      improved in vitro properties and further studies revealed that the compound had
      improved pharmacokinetic properties. 5. N-[[2'-[[(3,4-dimethyl-5
      isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]acetamide
      (4) was subsequently identified as a compound with superior in vitro properties
      compared with compound 3, but when tested in vivo it had a substantially
      increased rate of clearance. Further studies demonstrated that the clearance of
      this closely related structural analogue was not dictated by metabolic processes,
      but was mediated by transport-mediated direct biliary excretion. 6. The utility
      of screening for in vitro liver microsomal stability as part of the lead
      optimization process for compounds with metabolic liabilities was shown. It was
      also shown that relatively small molecular changes can dramatically change the
      disposition of closely related analogues and care must be used when screening for
      a single property.

PMID- 14660177
TI  - Sulfation of apomorphine by human sulfotransferases: evidence of a major role for
      the polymorphic phenol sulfotransferase, SULT1A1.
AB  - 1. The relative roles of various members of the human sulfotransferase (SULT)
      enzyme family in the metabolism of apomorphine, a dopamine receptor antagonist
      used in the treatment of Parkinson's disease and, more recently, erectile
      dysfunction, were examined. In humans, sulfation is the major route of metabolism
      of this drug. 2. Using recombinant SULTs expressed in Escherichia coli, R(--)
      apomorphine sulfation was studied using the universal barium precipitation assay
      in the presence of [35S] 3'-phosphoadenosine 5'-phosphosulfate and SULTs 1A1,
      1A2, 1A3, 1B1, 1C2, 1E1 and 2A1. It was shown that SULTs 1A1, 1A2, 1A3 and 1E1
      all sulfated apomorphine to varying extents. Low activity with SULT1B1 was only
      seen at the highest concentration (100 microM) and no activity with SULT1C2 or
      SULT2A1 was observed. 3. Kinetic analysis using purified recombinant SULTs showed
      that 1A1, 1A3 and 1E1 all had similar Vmax/Km values, although SULT1E1 had a
      slightly lower Km at around 1 microM compared with approximately 4 microM for the
      other SULTs. 4. By correlating apomorphine sulfation (at 10 microM) in a bank of
      28 liver cytosols with SULT activity towards 10 microM 4-nitrophenol (SULT1A1)
      and 0.2 microM 17beta-oestradiol (SULT1E1), a strong correlation with SULT1A1
      activity was clearly demonstrated, suggesting this enzyme was primarily
      responsible for hepatic apomorphine sulfation. 5. These findings were confirmed
      using immuno-inhibition experiments with antibodies against SULT1A and SULT1E1,
      which showed preferential inhibition of apomorphine sulfation in human liver
      cytosol by anti-SULT1A. 6. The results strongly implicate SULT1A1 as the major
      enzyme responsible for hepatic apomorphine metabolism. As SULT1A1 is subject to a
      common functional polymorphism, sulfation phenotype may be an important
      determinant of susceptibility to side-effects of apomorphine and/or efficacy of
      treatment.

PMID- 14660178
TI  - Bioavailability and half-life of decabromodiphenyl ether (BDE-209) in rat.
AB  - 1. The absorption of the flame retardant decabromodiphenyl ether (BDE-209) has
      been shown by its detection in human plasma, but reported experimental data on
      its determined in rat, and qualitative analyses by GC/MS of metabolites in plasma
      were performed. The relative amount of phenolic metabolites was determined in a
      rat plasma sample obtained after administration of radiolabelled BDE-209. 2. The
      bioavailability of parent BDE-209 was calculated to be about 26% in rat. The
      concentrations of phenolic radioactivity in plasma 3 and 7 days after dosing were
      four times higher than those of the neutral compounds, i.e. parent compound,
      indicating absorption in rat are inconsistent. The bioavailability and half-life
      were therefore that total absorption was higher than 26%. 3. Thirteen phenolic
      metabolites were determined in the plasma and the major phenolic metabolites were
      characterized as a hydroxy-octaBDE, a hydroxy-nonaBDE and a hydroxy-methoxy
      hexaBDE (guaiacol-type). The exposure to the phenolic metabolites seemed higher
      than the parent compound, BDE-209. 4. The initial elimination phase in plasma
      t1/2alpha for BDE-209 was 2 h, implying a rapid distribution of BDE-209 to well
      perfused tissues. The distribution volume at steady state was 1.4 l kg-1,
      implying a low tendency for distribution to adipose tissue. The terminal t1/2 for
      BDE-209 in the intravenously dosed rat was calculated as 2.5 days (58 h).

PMID- 14660179
TI  - Pharmacokinetics, metabolism and excretion of an inhibitor of inducible nitric
      oxide synthase, L-NIL-TA, in dog.
AB  - 1. The pharmacokinetics, metabolism and excretion of L-NIL-TA, an inducible
      nitric oxide synthase inhibitor, were investigated in dog. 2. The dose of [14C]L
      NIL-TA was rapidly absorbed and distributed after oral and intravenous
      administration (5 mg kg-1), with Cmax of radioactivity of 6.45-7.07 microg
      equivalents g-1 occurring at 0.33-0.39-h after dosing. After oral and intravenous
      administration, radioactivity levels in plasma then declined with a half-life of
      63.1 and 80.6-h, respectively. 3. Seven days after oral and intravenous
      administrations, 46.4 and 51.5% of the radioactive dose were recovered in urine,
      4.59 and 2.75% were recovered in faeces, and 22.4 and 22.4% were recovered in
      expired air, respectively. The large percentages of radioactive dose recovered in
      urine and expired air indicate that [14C]L-NIL-TA was well absorbed in dogs and
      the radioactive dose was cleared mainly through renal elimination. The mean total
      recovery of radioactivity over 7 days was approximately 80%. 4. Biotransformation
      of L-NIL-TA occurred primarily by hydrolysis of the 5-aminotetrazole group to
      form the active drug L-N6-(1-iminoethyl)lysine (NIL or M3), which was further
      oxidized to the 2-keto acid (M5), the 2-hydroxyl acid (M1), an unidentified
      metabolite (M2) and carbon dioxide. The major excreted products in urine were M1
      and M2, representing 22.2 and 21.2% of the dose, respectively.

PMID- 14660181
TI  - An analysis of medical device-related errors: prevalence and possible solutions.
AB  - The UK and USA are currently undergoing a period of considerable change in their
      attitude towards medical error and their understanding of its causes and
      magnitude. In both countries, with increasing rapidity, a disturbing situation is
      being revealed. This paper presents the results of an investigation into medical
      errors in the UK and the USA, and focuses in particular on the magnitude and
      causes of errors when using medical devices. Contrary to the traditional approach
      of blaming users, it is suggested here that many such errors are caused partly by
      poor device design, which fails to account adequately for the needs of users. In
      response, this paper also discusses the basics of a Human Factors Engineering
      (HFE) approach as a step towards overcoming this problem and offers a challenge
      to device users and design companies (manufacturers) to follow HFE principles in
      order to improve the efficiency of operation and reduce errors during device use.

PMID- 14660182
TI  - Utilization of temperature distribution in expiratory speaking flow as a new
      parameter for speech production analysis.
AB  - A new instrument with potential use for speech production analysis is utilized in
      this study to measure the temperature and velocity of the expiratory speaking
      flow outside the oral cavity. From a physical point of view, the temperature
      patterns of individuals with healthy voices are expected to be different from
      individuals with breathy voices, since their air flow patterns are different:
      during breathy speech production, the glottis does not close completely, and the
      leakage of warm air through the glottis increases the extent of the hotter-than
      ambient temperature field outside the oral cavity. The instrument is a pipe
      through which the tested individual breathes out while producing a sustained
      vowel. A tap water heat exchanger keeps the pipe wall at a temperature level
      considerably lower than the body temperature. The temperature gradient along the
      pipe centreline is measured and related to the average air velocity at the oral
      cavity. The measurements were performed in 30 male and 30 female subjects without
      vocal complaints. The objective of this initial investigation was to evaluate the
      possibility of establishing patterns of normality for the temperature
      distribution outside the oral cavity in expiratory speaking flow. In the
      experiments, all the temperature measurements increased as the expiratory air
      flow of the individual increased during speech production, therefore the
      instrument results agree with the physical behavior predicted by fluid mechanics
      and heat transfer principles. The collected data allowed for the construction of
      charts with two distinct normalized temperature distributions outside the oral
      cavity, for male and female individuals, respectively. These charts have the
      potential for future utilization in a follow-up study for comparison with similar
      measurements obtained with individuals with vocal fold pathologies, aiming to
      eventually produce a reliable new instrument for early detection of vocal
      problems through a non-invasive procedure.

PMID- 14660183
TI  - Neural network and fuzzy control in FES-assisted locomotion for the hemiplegic.
AB  - This study is aimed at establishing a neural network and fuzzy feedback control
      FES system used for adjusting the optimum electrical stimulating current to
      control the motion of an ankle joint. The proposed method further improves the
      drop-foot problem existing in hemiplegia patients. The proposed system includes
      both hardware and software. The hardware system determines the patient's ankle
      joint angle using a position sensor located in the patient's affected side. This
      sensor stimulates the tibialis anterior with an electrical stimulator that
      induces the dorsiflexion action and achieves the ideal ankle joint trace motion.
      The software system estimates the stimulating current using a neural network. The
      fuzzy controller solves the nonlinear problem by compensating the motion trace
      errors between the neural network control and actual system. The control
      qualities of various controllers for four subjects were compared in the clinical
      test. It was found that both the root mean square error and the mean error were
      minimal when using the neural network and fuzzy controller. The drop-foot problem
      in hemiplegic's locomotion was effectively improved by incorporating the neural
      network and fuzzy controller with the functional electrical simulator.

PMID- 14660185
TI  - When novel sentences spoken or heard for the first time in the history of the
      universe are not enough: toward a dual-process model of language.
AB  - Although interest in the language sciences was previously focused on newly
      created sentences, more recently much attention has turned to the importance of
      formulaic expressions in normal and disordered communication. Also referred to as
      formulaic expressions and made up of speech formulas, idioms, expletives, serial
      and memorized speech, slang, sayings, cliches, and conventional expressions, non
      propositional language forms a large proportion of every speaker's competence,
      and may be differentially disturbed in neurological disorders. This review aims
      to examine non-propositional speech with respect to linguistic descriptions,
      psycholinguistic experiments, sociolinguistic studies, child language
      development, clinical language disorders, and neurological studies. Evidence from
      numerous sources reveals differentiated and specialized roles for novel and
      formulaic verbal functions, and suggests that generation of novel sentences and
      management of prefabricated expressions represent two legitimate and separable
      processes in language behaviour. A preliminary model of language behaviour that
      encompasses unitary and compositional properties and their integration in
      everyday language use is proposed. Integration and synchronizing of two disparate
      processes in language behaviour, formulaic and novel, characterizes normal
      communicative function and contributes to creativity in language. This dichotomy
      is supported by studies arising from other disciplines in neurology and
      psychology. Further studies are necessary to determine in what ways the various
      categories of formulaic expressions are related, and how these categories are
      processed by the brain. Better understanding of how non-propositional categories
      of speech are stored and processed in the brain can lead to better informed
      treatment strategies in language disorders.

PMID- 14660186
TI  - Pragmatic language impairment and social deficits in Williams syndrome: a
      comparison with Down's syndrome and specific language impairment.
AB  - BACKGROUND: The social communication strength of individuals with Williams
      syndrome described by some researchers contrasts with the picture of social
      difficulties painted by others. AIMS: To study the pragmatic aspects of language,
      social relationships and unusual interests in a group of children and adults with
      Williams syndrome, and to compare them with a group of children and adults with
      Down's syndrome, children with specific language impairment, and a group of
      typically developing children. METHODS & PROCEDURES: Parents or teachers
      completed the Children's Communication Checklist or a modified version of it with
      wording appropriate for adults. Study groups consisted of 19 children and young
      adults with Williams syndrome, 24 with Down's syndrome, 17 children with specific
      language impairment and 32 typically developing children. OUTCOMES & RESULTS:
      Checklist ratings for the group with Williams syndrome indicated significant
      levels of pragmatic language impairment, and difficulties with social
      relationships. Together with evidence of unusual or restricted interests, the
      results suggested deficits across all three domains covered by the checklist.
      CONCLUSIONS: Despite earlier reports that emphasize a strong social interest and
      empathy, this study suggests that individuals with Williams syndrome have
      pragmatic language impairments, poor social relationships and restricted
      interests. Far from representing the polar opposite of autism, as suggested by
      some researchers, Williams syndrome would seem to share many of the
      characteristics of autistic disorder.

PMID- 14660187
TI  - Developmental perspectives on bilingual Swedish-Arabic children with and without
      language impairment: a longitudinal study.
AB  - BACKGROUND: There is a need for studies on bilingual language acquisition in
      combination with language impairment (LI). The speech and language clinician must
      have tools to differentiate between problems depending on inadequate exposure to
      a language and problems depending on a LI. Another important issue is the pace of
      bilingual language acquisition relative to the severity of LI. AIMS: To
      investigate grammatical development over 12 months in both languages in 10
      Swedish-Arabic pre-school children with severe LI and 10 Swedish-Arabic pre
      school children without LI. METHODS & PROCEDURES: The children were matched for
      age, gender, exposure to Swedish dialect, and exposure to Arabic dialect. The
      developmental hierarchy predicted by Processability Theory was used in tests in
      both Swedish and Arabic. Processability Theory was used as a yardstick to measure
      grammatical development in both languages. OUTCOME & RESULTS: Bilingual children,
      both with and without LI, developed grammatical structures in Swedish and Arabic
      in the same implicational way. Children with severe LI could develop two
      languages, although the pace of development was much slower in both languages.
      Bilingual children with severe LI were also more vulnerable to limited exposure
      of both their languages. CONCLUSIONS: A developmental perspective is important to
      understand the nature of LI in bilingual children. The results also have
      implications for the assessment of language development in bilingual children
      with severe LI, since a hardly perceptible development over time is observed.

PMID- 14660188
TI  - Investigations of the impact of altered auditory feedback in-the-ear devices on
      the speech of people who stutter: initial fitting and 4-month follow-up.
AB  - BACKGROUND: Self-contained ear-level devices delivering altered auditory feedback
      (AAF) for the application with those who stutter have only been recently
      developed. AIMS: The paper examines the first therapeutic application of self
      contained ear-level devices in three experiments. The effect of the device on the
      proportion of stuttered syllables and speech naturalness was investigated
      following initial fitting and at 4 months post-fitting. METHODS & PROCEDURES:
      Three experiments were undertaken: In Experiment 1, the effect of a self
      contained in-the-ear device delivering AAF was investigated with those who
      stutter during reading and monologue. Two adolescents and five adults who
      stuttered read and produced monologue with and without a device fit monaurally.
      The device provided a frequency shift of +500 Hz in combination with a delayed
      auditory feedback of 60 ms. Custom-made ITC and CIC devices were fabricated for
      four adults and four youths in Experiment 2. The effect of group (i.e. youth
      versus adult), time (i.e. initial fitting versus 4-month follow-up), speech task
      (i.e. reading versus monologue), and device (i.e. present versus absent) on
      stuttering rate was examined. In Experiment 3, 15 naive listeners rated the
      speech naturalness of speech produced by the participants in Experiment 2. Speech
      samples from six conditions were rated: reading and monologue without the device
      at the initial visit, reading and monologue with the device at the initial visit,
      and reading and monologue with the device at 4 months. OUTCOMES & RESULTS: In
      Experiment 1, the proportion of stuttered syllables was significantly (p=0.011)
      reduced by approximately 90% during reading and 67% during monologue with the
      device relative to no device. Only a significant main effect of device (p=0.0028)
      was found in Experiment 2. That is, stuttering rate was significantly reduced
      with the device in place regardless of speech task or group and remained so 4
      months later. In Experiment 3, speech samples generated while wearing the device
      were judged to be more natural sounding than those without the device (p<0.0001)
      for reading and monologue with both adults and youths. There was no significant
      difference between the mean naturalness ratings of speech samples generated
      during the initial fitting with the device relative to that at 4 months with the
      device (p>0.05) in all cases except with the youths while engaged in monologue.
      For that condition, raters judged the speech produced at the initial fitting as
      more natural. CONCLUSIONS: These findings support the notion that a self
      contained in-the-ear device delivering AAF assists those who stutter. With the
      device in place, stuttering is reduced and speech produced is judged to be more
      natural than with out the device.

PMID- 14660189
TI  - Sentence comprehension in children with specific language impairment: effects of
      input rate and phonological working memory.
AB  - BACKGROUND: Many children with specific language impairment (SLI) exhibit
      sentence comprehension difficulties. In some instances, these difficulties appear
      to be related to poor linguistic knowledge and, in other instances, to inferior
      general processing abilities. Two processing deficiencies evidenced by these
      children include reduced linguistic processing speed and diminished phonological
      working memory (PWM) capacity. While providing children with SLI a slower input
      rate appears to facilitate their immediate (real-time) processing of language; it
      is not known whether such a manipulation might also promote better offline
      (conventional) sentence comprehension. Complicating the potential benefits of a
      slower input rate on these children's offline comprehension is that a slower
      input rate might negatively interact with their PWM deficit. That is, a slower
      presentation rate may have the unintended consequence of placing too great a
      temporal burden on these children's vulnerable PWM system, thereby leading to
      even poorer comprehension. That is, a slower input rate presumably requires the
      listener to store previously processed information for a longer period while new,
      incoming material is being processed. AIMS: To investigate the interaction of
      input rate and PWM capacity on the sentence comprehension of children with SLI.
      It was hypothesized that if a slower input rate negatively affects the PWM
      functioning of children with SLI, these children would comprehend significantly
      fewer sentences presented at a slower rate versus sentences presented at a normal
      rate. It was also hypothesized that input rate should have no differential effect
      on the typically developing control children. METHODS & PROCEDURES: A group of 12
      school-age children with SLI, a group of 12 age-matched children (CA), and a
      group of 12 receptive syntax-matched (RS) children (all with normal-range non
      verbal IQ and hearing) completed a conventional picture-pointing sentence
      comprehension task. Sentences were presented at a normal speaking rate and a
      slower rate (25% time expanded). Children also completed a non-word repetition
      task, which served as an index of PWM capacity. OUTCOMES & RESULTS: Results of
      the PWM task revealed that the children with SLI repeated fewer three- and four
      syllable non-words than both the CA and RS children, suggesting they had reduced
      PWM capacity. On the sentence comprehension task, a significant group by input
      rate interaction emerged. The children with SLI yielded significantly poorer
      comprehension of normal-rate sentences compared with both the CA and RS children.
      Whereas input rate had no differential effect on CA and RS children's
      comprehension, the comprehension of the children with SLI improved to the level
      of RS children in the slow-rate condition. Correlational analyses showed no
      significant association between PWM and sentence comprehension in either rate
      condition for any of the groups. CONCLUSIONS: Together, these findings suggest
      that the simple manipulation of altering speaking rate to children with SLI
      indeed can facilitate sentence comprehension, with no apparent detrimental effect
      on the operations of their PWM system.

PMID- 14660190
TI  - Becoming a manual occupation? The construction of a therapy manual for use with
      language impaired children in mainstream primary schools.
AB  - BACKGROUND: The construction of therapy protocols for a large-scale randomized
      controlled trial comparing speech and language therapists and assistants, and
      group and individual therapy approaches for children aged 6-11 in mainstream
      schools is outlined. AIMS: The aim was to outline the decision-making processes
      that led to the construction of the research therapy manual, and to give a
      preliminary report on compliance with the manual. METHODS & PROCEDURES: A search
      of the research and professional literature and of published therapy materials
      was conducted to locate usable examples of effective language therapy for primary
      school children. Results were collated into a manual of therapy principles and
      activities to structure research intervention. The use of the manual with
      children (n=30) receiving individual or group direct therapy from a speech and
      language therapist in the first phase of intervention was audited. OUTCOMES &
      RESULTS: Very few high-level research studies were found, but the professional
      literature gave added information. Therapies for comprehension monitoring,
      vocabulary development, later grammar and narrative were adapted for the research
      intervention, and procedures compiled into a manual to guide research speech and
      language therapists and assistants. The audit of direct therapy suggested that
      the manual was useable, providing a suitable range of activities and materials
      for therapy intervention. Its use helped to record the therapy offered to
      research children, and formed a sound basis for discussion amongst speech and
      language therapists and between speech and language therapist/assistant pairs.
      CONCLUSIONS: The construction and use of a therapy manual allowed the provision
      of replicable therapy within the research project whilst maintaining flexibility.

PMID- 14660192
TI  - Theoretical aspects of goal-setting and motivation in rehabilitation.
AB  - PURPOSE: The purpose of this article is to provide rehabilitation theorists and
      researchers with an introduction to some key theories of goals and motivation
      from the field of social cognition and to argue for increased dialogue between
      the two disciplines. METHOD: The use of goals and goal-setting in rehabilitation
      is briefly surveyed and the somewhat ambivalent attitude toward the concept of
      motivation in the rehabilitation literature is highlighted. Three major
      contributors to the study of goals and motivation from the field of social
      cognition are introduced and their work summarized. They include: (i) Deci and
      Ryan's Self-Determination Model; (ii) Emmons' work on goals and personal
      strivings, and (iii) Karniol and Ross' discussion of temporal influences on goal
      setting. RESULTS: It is argued that there is a need for a greater emphasis upon
      theory development in rehabilitation research and that closer collaboration
      between researchers in rehabilitation and social psychology offers considerable
      promise. Instances where the three theories from social cognition might have
      relevance to clinical rehabilitation settings are described. Some possible
      directions for research are also briefly sketched. CONCLUSION: Both
      rehabilitation and social cognition have much to gain from increased dialogue.

PMID- 14660193
TI  - Neck discomfort of wheelchair users: effect of neck position.
AB  - PURPOSE: To test the hypothesis that wheelchair users experience more discomfort
      when holding their necks in extended and/or rotated positions than when in their
      self-selected most comfortable positions (MCPs). METHODS: We studied 20
      wheelchair users, first determining their MCPs with the eyes closed. Then,
      subjects assumed and maintained (for 5 min each) four neck positions in random
      order: level (L) and elevated (E), both straight ahead of the subject (S) and
      with the neck rotated (R). We measured neck extension angles (from digital
      photographs) and neck discomfort (using visual analogue scales [VAS], in %).
      RESULTS: The mean neck-extension angles were MCP - 2.6 degrees, LS 9.5 degrees,
      LR 8.1 degrees, ES 23.9 degrees and ER 25.4 degrees (ANOVA p < 0.0001). The mean
      VAS neck discomfort scores were LS 5.7%, LR 17.4%, ES 24.0% and ER 34.1% (ANOVA p
      < 0.0001). CONCLUSIONS: Sustained extension and rotation of the neck, alone or in
      combination, increase the neck discomfort of wheelchair users. The MCP for most
      wheelchair users is straight ahead with the neck slightly flexed, about 11
      degrees and 27 degrees more flexed, respectively, than when looking at an average
      height sitting or standing person. These findings have implications for
      wheelchair design, the behaviour of clinicians and wheelchair users, and the
      built environment.

PMID- 14660194
TI  - Service providers' perception of affective influences on decision-making about
      treatments for chronic pain.
AB  - PURPOSE: Service providers working with people who have complex health problems
      like chronic pain are considered at particular risk from the heavy emotional
      content of these interactions (frustration, guilt, hostility). For the good of
      service users and in the interests of healthcare workers' own health it is
      important for them to employ reflective practice acknowledging these issues.
      Service providers are inculcated to negate the affective domain of their practice
      despite the growing awareness that wellbeing can no longer be envisioned as a
      linear (cause and effect) process divorced from socio-cultural influences and
      attendant values and beliefs. The aim of this report is to examine to what degree
      service users (SU) and service providers (SP) believe their decisions about
      treatment importance are influenced by self-image and emotion. DESIGN: These
      results are extrapolated from a larger study based on a postal questionnaire that
      went to members of the Pain Society (UK Chapter of IASP) and service users
      belonging to chronic pain support groups in the North-West of England. The
      question of interest in this report asked participants to identify their level of
      agreement with statements about how four themes influence their decision-making
      about whether a treatment is important. The themes (coherence, purposiveness,
      self-image and affect) arise from Chapman's model of consciousness and pain.
      RESULTS: Only 20.5% of service providers rated the influence of self-image (what
      someone like me would think) as 3 (mostly) or 4 (completely). Service provider
      rating for the influence of affect (how this treatment makes me feel) were
      similarly low with only 19.4% of respondents selecting a rating of 3 or 4. In
      marked contrast, 73.3% of the service users selected self-image and 92.9%
      selected affect as a strong influence. CONCLUSION: Service providers felt that
      affect and self-image had little influence on their decision-making. However,
      there is growing evidence in the literature to suggest that it is not possible,
      nor preferable, to divorce emotion from the clinical encounter.

PMID- 14660195
TI  - The influence of seat adjustment and a thoraco-lumbar-sacral orthosis on the
      distribution of body-seat pressure in children with scoliosis and pelvic
      obliquity.
AB  - PURPOSE: To determine the effect of a thoraco-lumbar-sacral orthosis (TLSO) on
      the distribution of body-seat interface pressure in children with concomitant
      scoliosis and pelvic obliquity and to determine the effects of two methods
      commonly used in customized seating--elevation (push up) of the lower side of the
      pelvis or a wedge insertion beneath the raised pelvis--on the distribution of
      body-seat interface pressure. METHODS: The study population comprised 15 children
      with an underlying neuromuscular disorder. All had scoliosis and pelvic obliquity
      when seated, and used a TLSO during sitting. Body-seat interface pressure was
      measured using the QA Pad. Maximum pressure, mean pressure and contact area were
      recorded at baseline and at 10 degrees 'push up' and 10 degrees wedge insertion,
      with and without the TLSO. X-rays were performed with and without the orthosis at
      baseline position. RESULTS: The TLSO reduced the scoliosis deformity by a mean of
      5.3 degrees and significantly (p < 0.05) reduced the mean pressure and contact
      area in the sub-group of patients whose pelvic obliquity was contralateral to the
      side of the curve. Seat adjustment did not have any significant effect on
      pressure readings. CONCLUSION: Application of a TLSO in a child with scoliosis
      and contralateral pelvic obliquity significantly reduced the spinal curvature and
      interface sitting pressure. Manipulation of sitting by use of wedges under the
      pelvis had no significant effect on pressure distribution.

PMID- 14660196
TI  - A long time getting home: Vietnam Veterans' experiences in a community exercise
      rehabilitation programme.
AB  - PURPOSE: We aimed to qualitatively evaluate the experiences of a group of 14
      Australian Vietnam Veterans, including five who stated being diagnosed with
      Posttraumatic Stress Disorder, participating in a 40-week exercise programme.
      METHOD: The veterans provided prospective feedback on perceptions, attitudes and
      opinions related to the programme via a series of three focus groups. A content
      analysis using the grounded theory approach was used to categorize the main
      themes to emerge from the transcribed data. RESULTS: The main findings included
      (a) the group's perceived lifestyle prior to participating in the programme, such
      as working long hours, social isolation and low motivation levels, (b) lifestyle
      and psychological changes as a result of the exercise programme, such as
      decreased anger levels, increased mental awareness, energy levels and daily
      resilience, and (c) increased social support. The veterans nominated the
      interaction and support arising from the classes, in addition to participation in
      the exercise per se, as being associated with the perceived benefits in personal
      lifestyle. CONCLUSIONS: The findings suggest that physical activity programmes
      set up within the community specifically for Vietnam Veterans may benefit them
      psychologically as well as physically.

PMID- 14660197
TI  - Chronic physical health conditions and disability among Canadian school-aged
      children: a national profile.
AB  - OBJECTIVE: The objective of this study was to provide a national health and
      disability profile of Canadian school-aged children based on the World Health
      Organization's definitions of health condition and disability that would
      facilitate international comparisons of child health data. METHODS: Data were
      used from the National Longitudinal Survey of Children and Youth, a 1994 - 95
      population-based sample of 22 831 children. FINDINGS: An estimated total of 30.3%
      of Canadian children aged 6 to 11 had one or more chronic physical health
      conditions/impairments, while 3.6% had activity-limiting conditions/impairments.
      Children living with one parent were significantly more likely to have activity
      limiting conditions/impairments than those living with two parents. Children with
      conditions/impairments, particularly those with activity limitations, were
      significantly more likely than children without health problems to have
      experienced mental health conditions and learning disabilities, missed school
      days, received special education, visited health professionals, been
      hospitalized, and used prescription medication. CONCLUSION: Important differences
      were found among children in a number of areas as a function of overall physical
      health status. The findings emphasize the importance of measuring activity
      limitations distinctly from chronic conditions and impairments, and, perhaps, of
      measuring impairments distinctly from chronic conditions, and of comparing
      children with such health problems to children without health problems in order
      to obtain a more accurate picture of the impact of health on children's lives.
      The World Health Organization's distinct definitions of health condition and
      disability facilitate a dimensional approach for describing child health that can
      serve to clarify this field of study and improve comparability of data across
      countries.

PMID- 14660198
TI  - Recovery from fibromyalgia - previous patients' own experiences.
AB  - PURPOSE: To explore what patients that had completely recovered from fibromyalgia
      (FM) experienced as being important for their recovery. METHODS: Five women, aged
      between 37 and 49 were interviewed individually. The interviews were aimed at
      finding out about the recovery process and the women's daily lives at the time of
      the interview and before and after their diagnosis, with a special emphasis on
      social relationships and obligations. The interviews were analysed by qualitative
      thematic content analysis. RESULTS: These five women reported that they recovered
      irrespective of specific treatment. The study shows that resistance to the
      unpleasantness of the sick role and the stigmatization associated with the
      uncertain nature of the FM diagnosis promoted recovery. Instead of adapting their
      activities to pain, they used pain as a warning signal of too much stress in
      life. This significantly developed their ability to alter their life goals and
      everyday obligations. At the same time they managed to maintain a social role
      they considered to be consistent with their self-image. CONCLUSIONS: Patients can
      recover from FM. The information from these informants suggests that to struggle
      against a role of chronic patient and keep up with their social obligations and
      goals were of great importance.

PMID- 14660199
TI  - School bag carriage and pain in school children.
AB  - PURPOSE: In South Africa (SA), anecdotal evidence for the incidence of shoulder,
      back and neck pain in school children is alarming but no scientific studies have
      confirmed this impression. The purpose of the present study was to determine the
      relationship between pain and school bag carriage in scholars in Durban, SA.
      METHOD: A study was carried out at four different schools in the Verulam and
      Chatsworth Regions in Kwa-Zulu Natal, SA. Schools were selected by convenience.
      One hundred and seventy six scholars between the ages of 11 and 14 years
      correctly filled out a questionnaire with open-ended and closed-ended questions.
      Each child also had his/her body and bag weight measured. RESULTS: In this study,
      most of the scholars experienced shoulder and a combination of shoulder and other
      bodily pain. The majority of the children carried backpacks over two shoulders.
      The type of bag carried was significantly related to pain experienced (0.00). A
      significantly larger number of female scholars experienced pain. CONCLUSION: The
      shoulder and other bodily pain experienced by the sample of scholars are strongly
      related to the type of bag and the gender of the children. More in-depth studies
      into identifying risk factors for bodily pains in school children are indicated.

PMID- 14660200
TI  - Evaluation of prosthetic usage in upper limb amputees.
AB  - PURPOSE: Upper limb amputations cause severe functional disability and lower the
      patient's self body image, with severe psychological implications. Many
      parameters are involved in the successful rehabilitation of upper limb
      amputations. The aim of this study was to investigate whether there are any
      parameters that might predict the successful prosthetic rehabilitation of upper
      limb amputees. METHOD: The records of 45 patients who had undergone an upper limb
      amputation were traced. The patients were evaluated according to four parameters:
      (1) Modified upper extremities amputees' questionnaire; (2) Pain level according
      to Visual Analog Scale (VAS), range from 1 (lowest) up to 10 (highest); (3) Pain
      type - phantom or pain in the stump; (4) Functional assessment of prosthetic
      usage. RESULTS: Thirty (71.43%) of the patients reported difficulties with
      prosthesis usage. Twenty-three patients (54.76%) were satisfied with their
      prosthesis - 19 had cosmetic prosthesis and four had body-powered prosthesis.
      CONCLUSION: No significant affect of the amputation level except for trans-wrist
      amputation with 100% prosthesis use. No significant difference was found between
      prosthesis type and the correlation to stump problems. The above-elbow amputees,
      with dominant hand amputation, who used functional prosthesis (body-powered),
      achieved the best functional outcome and result.

PMID- 14660201
TI  - Intermanual difference in the Japanese Trail Making Test and its mirror version:
      intra-subject comparison of the task-completion time, cognitive time, and motor
      time.
AB  - PURPOSE: To investigate intermanual differences in the performance of the
      Japanese Trail Making Test (JTMT) using an intra-subject comparison, and to
      investigate how the cognitive and motor times spent in performing the task were
      related with the total completion time. METHODS: All subjects performed both
      parts A and B of the following three tasks: JTMT with the right hand (R); JTMT
      with the left hand (L); and a mirror version of the JTMT with the left hand (M).
      The order in which these three tasks were performed (RLM, RML, LRM, LMR, MRL, and
      MLR) was randomly determined. An interval of 4 weeks was scheduled between each
      examination. In addition to the completion time, we measured 'motor time', a sum
      of the times for drawing lines to connect the targets, and 'cognitive time', a
      time obtained by subtracting the motor time from the completion time. RESULTS:
      The task-completion time was more strongly correlated with the cognitive time
      than with the motor time. The order of the task performance did not influence the
      task-completion time. A learning effect was found only between the first and
      second examinations of part A. The cognitive time for the second and third
      performances of part A were significantly shorter than that for the first task,
      whereas the motor time remained unchanged. No intermanual differences in the
      performance were found in any comparisons. CONCLUSIONS: The non-dominant hand can
      be used as an alternative hand in the JTMT, and it can be expected to perform
      comparably to the dominant hand. These findings are consistent with the finding
      previously obtained by inter-subject comparison. The lack of any significant
      intermanual difference can be explained by that the total completion time is less
      influenced by the motor time than by the cognitive time.

PMID- 14660202
TI  - Assessing the additional impact of fitness training in depressed psychiatric
      patients receiving multifaceted treatment: a replicated single-subject design.
AB  - PURPOSE: Exercise has been put forward as a therapeutic means for the treatment
      of clinical depression. METHODS: In this study, 29 patients, all with diagnosed
      with mood disorder, completed daily measurements of depression and physical well
      being during periods ranging from 77 to 436 days (M = 146.5). Fitness training
      was added to the treatment after a period and changes before (A-phase) and after
      (B-phase) the implementation of this training were the subject of investigation.
      Data were analysed by means of randomization tests with an AB-design and time
      series analysis. Replication of the findings was investigated using Fisher's
      multiplicative method. RESULTS: Adding fitness training to the treatment of
      clinical depression does not systematically lead to changes in self-reported
      feelings of depression on top of benefits that may be due to other treatments.
      CONCLUSIONS: Since the present findings are not in agreement with previous
      studies, the absence of statistically significant changes in self-reported
      feelings of depression is discussed within the complexity of the 'exercise -
      depression' relationship in inpatient populations. These included the severity of
      their depression, the potential ceiling effect of a multifaceted treatment
      programme and the initial increase in depression due to the confrontational
      nature of the intervention.

PMID- 14660203
TI  - Surveillance of discriminatory attitudes toward people living with HIV/AIDS among
      the general public in Hong Kong from 1994 to 2000.
AB  - PURPOSE: This study monitored the level of discriminatory attitudes toward people
      living with HIV/AIDS (PLWHA) exhibited by the general public in Hong Kong from
      1994 to 2000. METHODS: A series of six cross-sectional telephone surveys using an
      identical method and a structured questionnaire were conducted. A total of 6,795
      respondents aged 18 - 50 randomly selected from the general population
      participated in the study. RESULTS: Over the study period, the level of
      discriminatory attitudes toward PLWHA exhibited by the public has been improved
      slightly. For instance, fewer respondents in 2000 (10.6%) than in 1994 (21.8%)
      agreed that an HIV infected person should move out of the household (chi(2) test
      for trend, p < 0.001). However, there remained about one third who would avoid a
      friend infected with HIV (chi(2) test for trend, p < 0.05). Logistic regression
      analysis demonstrated that misconceptions about HIV transmission routes remained
      strongly associated with the discriminatory attitudes toward PLWHA; other
      significant factors included exposure to TV Announcement of Public Interest on
      HIV/AIDS-related issues and perceived chance of HIV infection as a result of
      having homosexual behaviours. CONCLUSIONS: Though some improvement has been
      observed, the level of discriminatory attitudes is still high. Sustained
      education to remove misconceptions about HIV infection is much required.

PMID- 14660204
TI  - Improving spatial functioning in children with cerebral palsy using computerized
      and traditional game tasks.
AB  - PURPOSE: To examine the effectiveness of combining virtual environment (VE)
      instruction with additional desk-top tasks, based on the Luria-Vygotsky
      methodology, for spatial remediation in children having complex motor
      disabilities restricting movement. METHODS: In Experiment 1, from among children
      attending for residential rehabilitation, an experimental subgroup had additional
      spatial training using a VE and corresponding desk-top models. All children were
      tested at the start and end of training, using four spatial tests. In Experiment
      2, larger groups of children (pair-matched for initial performance) were given
      the same training as in Experiment 1, but experimentals received both VE-based
      training and supporting tasks designed to improve executive functions and verbal
      regulation of spatial functioning. Assessment involved a wider range of tests
      than in Experiment 1. RESULTS: In Experiment 1, both groups showed improvement at
      retest, but experimentals showed greater improvement. Children beginning with the
      lowest level of cognitive performance failed to benefit from the additional
      training. In Experiment 2 the experimental group made significantly greater
      improvement than controls, irrespective of initial performance level.
      CONCLUSIONS: VE-based spatial training is effective for children with complex
      disabilities, particularly when combined with training that remediates cognitive
      weaknesses.

PMID- 14660205
TI  - Physiotherapy group treatment for patients with fibromyalgia--an embodied
      learning process.
AB  - PURPOSE: To study how patients with fibromyalgia (FM) experienced physiotherapy
      group treatment comprising pool exercise and education. METHODS: Nineteen
      patients with FM were interviewed and the transcribed interviews were analysed
      using a phenomenological life-world approach. The participants' mean age was 45
      years and their mean symptom duration was 10 years. RESULTS: Physiotherapy group
      treatment was experienced as an embodied learning process, comprising the themes:
      positive experience of body, sharing experiences of living with FM and creating
      new patterns of acting. The positive experience of body comprised the following
      categories: experiencing relaxation, experiencing physical capacity,
      acknowledging limitations and changing the pattern of activity. Sharing
      experiences comprised the following categories: not being alone and sharing joy.
      Three patterns of participation were identified: reciprocity, distancing and
      remaining outside. Creating new patterns comprised the following categories;
      calming down, creating a new relationship to self, creating a new relationship to
      social roles and creating new patterns for managing pain. CONCLUSIONS: The study
      indicates that physiotherapy group treatment was experienced as an embodied
      learning process. Positive experiences of body were intertwined with a new
      relationship to self and objects in the world. Interactions between the co
      participants promoted the process of creating new patterns of thinking and acting
      in the social world.

PMID- 14660206
TI  - Socio-demographical examinations on disability prevalence and rehabilitation
      status in southwest of Turkey.
AB  - PURPOSE: Disability is one of the most important social issues in the community.
      In contrast to the developed countries, Turkey has, unfortunately, no goods
      records on the current issues of disability such as the number of disabled and
      handicapped, and their socio-demographic properties due to the lack of sufficient
      studies in the specified area. The present study was, therefore, aimed to
      determine the status of disabled in the entire region of Isparta and to establish
      relationships between the distinctive disability properties in order for a better
      understanding of its important aspects. MATERIALS AND METHODS: Data were
      collected in 2002 from 3500 people residing throughout the region by the gradual
      sampling method according to the evaluation criteria of International
      Classification of Impairments, Disabilities and Handicaps (ICIDH) by WHO.
      RESULTS: The disability prevalence in the studied group was found to be 5.3%, and
      4.8% of the disabled were previously rehabilitated. Forty one percent of the
      disabled were found to have two types of disability. In the study, it was shown
      that the disability prevalence significantly increased by the age. The disabled
      were shown to be under-educated and not benefit from the rehabilitation services
      in one hand, and there were insufficient activities of rehabilitation established
      in the region in other hand. CONCLUSIONS: We concluded that the medical and
      social rehabilitation services must be initiated and freely provided to these
      local people, particularly to those young disables whose life will greatly change
      to a better living standard.

PMID- 14660208
TI  - Physical workload during use of speech recognition and traditional computer input
      devices.
AB  - Musculoskeletal symptoms among computer users are frequently found. The aim was
      to investigate the musculoskeletal workload during computer work using speech
      recognition and traditional computer input devices (keyboard/mouse). Ten
      experienced computer users (nine female, one male) participated. They performed
      three different computer tasks: (1). text entry and (2). text editing of a
      standard text and (3). a self-selected work task. These tasks were performed
      twice using speech recognition and traditional computer input devices
      (keyboard/mouse). Additionally, a task consisting of reading aloud of the
      standard text was performed. Surface EMG from the forearm (m. extensor carpi
      ulnaris, m. extensor carpi radialis), the shoulder (m. trapezius) and the neck
      extensor muscles was recorded, in addition to the voice-related muscles (m.
      scalenii, m. cricothyroideus). Using speech recognition during text entry and
      text editing reduced the static muscle activity of the forearm, neck and to some
      extent the shoulder muscles. Furthermore, tendencies to longer periods of muscle
      activity pause (relative time with EMG gaps) in the forearm and shoulder muscles
      were found. This was seen at the expense of a tendency to an increased static
      activity and a decreased relative time with EMG gaps in m. cricothyroideus.
      Finally, during use of speech recognition the hand was tied to the keyboard/mouse
      for a shorter period of time, while the eyes were viewing the screen for a longer
      period of time compared to the condition with traditional computer input devices.
      It is recommended to use speech recognition as a supplementary tool to
      traditional computer input devices.

PMID- 14660209
TI  - Activity theory as a basis for the study of work.
AB  - Activity theory has been successfully applied in diverse schools of psychology
      with particularly extensive work in the fields of education, ergonomics, human
      factors and industrial-organizational psychology. However, existing efforts of
      translation and formulation in English suffer from certain limitations. These
      limitations include the blurring between Vygotsky's socio-cultural theory of the
      development of mind and activity theory, the restriction of activity theory in
      its entirety to the version offered by Leont'ev, errors in the interpretation of
      some basic concept and terminology, reliance on studies that use obsolete
      methods, and failure to consider the Russian work in activity theory in its
      entirety. This last problem results in the omission of the recent advances in
      engineering psychology and educational psychology in the former Soviet Union that
      facilitates the application of activity theory to practical problems. This paper
      is a description of the evolution of basic theory, concepts and terminology
      relevant to practitioners--particularly in the field of ergonomics.

PMID- 14660210
TI  - Adaptation of performance during a week of simulated night work.
AB  - This study aimed to provide a comparative index of the performance impairment
      associated with the fatigue levels frequently experienced in workplaces that
      require night work. To do this, we equated fatigue-related impairment with the
      impairment resulting from varying levels of alcohol intoxication. Fifteen young
      individuals participated in two counterbalanced conditions which required them to
      (1). 'work' seven consecutive 8-h night shifts, and (2). consume an alcoholic
      beverage at hourly intervals until their blood alcohol concentration (BAC)
      reached 0.10%. In each condition, performance was measured at hourly intervals
      using a 10-min psychomotor vigilance task (PVT). Analysis indicated that as BAC
      increased, performance impairment significantly increased. Similarly, response
      times significantly increased during the first six simulated night-shifts, and
      lapse frequency significantly increased during the first two shifts. Equating the
      two conditions indicated that the first simulated night shift was associated with
      the greatest degree of performance impairment. In general, the impairment at the
      end of this shift was greater than that observed at a BAC of 0.10%. During the
      second and third simulated night shifts, the performance impairment was less than
      on the first night, but greater than that observed at a BAC of 0.05%. For the
      final four nights, the performance decrements generally did not exceed those
      observed at a BAC of 0.05%. This suggests that during a week of consecutive night
      shifts, adaptation of performance occurs.

PMID- 14660211
TI  - A randomized and controlled trial of a participative ergonomics intervention to
      reduce injuries associated with manual tasks: physical risk and legislative
      compliance.
AB  - A participative ergonomics approach to reducing injuries associated with manual
      tasks is widely promoted; however only limited evidence from uncontrolled trials
      has been available to support the efficacy of such an approach. This paper
      reports on a randomized and controlled trial of PErforM, a participative
      ergonomics intervention designed to reduce the risks of injury associated with
      manual tasks. One hundred and seventeen small to medium sized food, construction,
      and health workplaces were audited by government inspectors using a manual tasks
      risk assessment tool (ManTRA). Forty-eight volunteer workplaces were then
      randomly assigned to Experimental and Control groups with the Experimental group
      receiving the PErforM program. Inspectors audited the workplaces again, 9 months
      following the intervention. The results showed a significant decrease in
      estimates of manual task risk and suggested better legal compliance in the
      Experimental group.

PMID- 14660212
TI  - Perceived physical stress at work and musculoskeletal discomfort in X-ray
      technologists.
AB  - A structured questionnaire/interview was designed to explore demographic,
      personal, occupational and occupational health factors as well as recreational
      physical activities which can affect X-ray technologists' musculoskeletal
      symptoms. This questionnaire was piloted for clarity and validity. Subsequently,
      a random sample of 20 volunteer participants (18 female, 2 male) from two
      University hospitals were administered the questionnaire in the presence of the
      investigators to ensure that questions were correctly understood. The data
      obtained were analysed for magnitude, duration and frequency of activities and
      for severity, duration and recurrence of morbidity. The X-ray technologists in
      the sample were found to be a young group of professionals ranging from between
      20 - 54 years of age. Eighty-nine per cent of the technologists were physically
      active and 44% indulged in physical recreational activities. Despite the young
      age and active life style, the X-ray technologists had significant and diverse
      musculoskeletal problems; 83% of technologists had backache and 39% of the female
      technologists had neck pain and 28% shoulder pain. The majority of technologists
      had suffered multiple episodes of pain. Fifty per cent of the female sample and
      both male volunteers suffered from upper extremity pain.

PMID- 14660213
TI  - Effects of precision demands and mental pressure on muscle activation and hand
      forces in computer mouse tasks.
AB  - The objective of the present study was to gain insight into the effects of
      precision demands and mental pressure on the load of the upper extremity. Two
      computer mouse tasks were used: an aiming and a tracking task. Upper extremity
      loading was operationalized as the myo-electric activity of the wrist flexor and
      extensor and of the trapezius descendens muscles and the applied grip- and click
      forces on the computer mouse. Performance measures, reflecting the accuracy in
      both tasks and the clicking rate in the aiming task, indicated that the levels of
      the independent variables resulted in distinguishable levels of accuracy and work
      pace. Precision demands had a small effect on upper extremity loading with a
      significant increase in the EMG-amplitudes (21%) of the wrist flexors during the
      aiming tasks. Precision had large effects on performance. Mental pressure had
      substantial effects on EMG-amplitudes with an increase of 22% in the trapezius
      when tracking and increases of 41% in the trapezius and 45% and 140% in the wrist
      extensors and flexors, respectively, when aiming. During aiming, grip- and click
      forces increased by 51% and 40% respectively. Mental pressure had small effects
      on accuracy but large effects on tempo during aiming. Precision demands and
      mental pressure in aiming and tracking tasks with a computer mouse were found to
      coincide with increased muscle activity in some upper extremity muscles and
      increased force exertion on the computer mouse. Mental pressure caused
      significant effects on these parameters more often than precision demands.
      Precision and mental pressure were found to have effects on performance, with
      precision effects being significant for all performance measures studied and
      mental pressure effects for some of them. The results of this study suggest that
      precision demands and mental pressure increase upper extremity load, with mental
      pressure effects being larger than precision effects. The possible role of
      precision demands as an indirect mental stressor in working conditions is
      discussed.

PMID- 14660214
TI  - Adaptive strategy changes as a function of task demands: a study of car drivers.
AB  - When drivers perform additional tasks while driving, research shows conflicting
      results: primary driving performance may deteriorate but adaptive changes such as
      reducing driving speed have also been noted. We hypothesized that the nature of
      the secondary task may be important: drivers may give more priority to tasks that
      serve goals of the driving task itself, for example route finding, than tasks not
      directly relevant for driving, for example tuning the radio. The main objective
      of the present driving simulator study was to test this hypothesis. Twenty
      subjects performed two different subsidiary tasks while driving through two
      levels of traffic density: a working memory (WM) task and a map reading (MAP)
      task. It was hypothesized that in high task demand situations, the WM task,
      irrelevant for the driving task, would be neglected more than the MAP task. The
      results confirmed the hypothesis: in MAP conditions, the WM task was indeed
      neglected, but map reading resulted in more swerving, indicating that the
      subjects looked at the map despite the high task demands. It is concluded that
      drivers will be highly motivated to get route information, and RG systems should
      therefore present their information in a readily understandable format.

PMID- 14660215
TI  - Mechanical loading of the low back and shoulders during pushing and pulling
      activities.
AB  - The objective of this study was to quantify the mechanical load on the low back
      and shoulders during pushing and pulling in combination with three task
      constraints: the use of one or two hands, three cart weights, and two handle
      heights. The second objective was to explore the relation between the initial and
      sustained exerted forces and the mechanical load on the low back and shoulders.
      Detailed biomechanical models of the low back and shoulder joint were used to
      estimate mechanical loading. Using generalized estimating equations (GEE) the
      effects were quantified for exerted push/pull forces, net moments at the low back
      and shoulders, compressive and shear forces at the low back, and compressive
      forces at the glenohumeral joint. The results of this study appeared to be useful
      to estimate ergonomics consequences of interventions in the working constraints
      during pushing and pulling. Cart weight as well as handle height had a
      considerable effect on the mechanical load and it is recommended to maintain low
      cart weights and to push or pull at shoulder height. Initial and sustained
      exerted forces were not highly correlated with the mechanical load at the low
      back and shoulders within the studied range of the exerted forces.

PMID- 14660216
TI  - Job enlargement and mechanical exposure variability in cyclic assembly work.
AB  - Cyclic assembly work is known to imply a high risk for musculoskeletal disorders.
      To have operators rotate between work tasks is believed to be one way of
      decreasing this risk, since it is expected to increase variation in mechanical
      and psychological exposures (physical and mental loads). This assumption was
      investigated by assessing mechanical exposure variability in three assembly tasks
      in an electronics assembly plant, each on a separate workstation, as well as in a
      'job enlargement' scenario combining all three stations. Five experienced
      operators worked for 1 h on each station. Data on upper trapezius and forearm
      extensor muscle activity were obtained by means of electromyography (EMG), and
      working postures of the head and upper arms were assessed by inclinometry. The
      cycle-to-cycle variance of parameters representing the three exposure dimensions:
      level, frequency and duration was estimated using ANOVA algorithms for each
      workstation separately as well as for a balanced combination of all three. For a
      particular station, the variability of trapezius EMG activity levels relative to
      the mean was higher than for extensor EMG: between-cycles coefficients of
      variation (CV) about 0.15 and 0.10, respectively. A similar relationship between
      CV applied to the parameter describing frequency of EMG activity. Except for head
      inclination levels, the between-cycles CV was larger for posture parameters than
      for EMG. The between-cycles variance increased up to six fold in the job
      enlargement scenario, as compared to working at only one station. The difference
      in mean exposure between workstations was larger for trapezius EMG parameters
      than for forearm extensor EMG and postures, and hence the effect of job
      enlargement on exposure variability was more pronounced for the trapezius. For
      some stations, job enlargement even implied less cycle-to-cycle variability in
      forearm extensor EMG parameters than working at that station only. Whether the
      changes in exposure variability associated with job enlargement were sufficient
      to imply a decreased risk for musculoskeletal disorders is not known.

PMID- 14660217
TI  - Measurement of prehensile grasp capabilities by a force and moment wrench:
      methodological development and assessment of manual workers.
AB  - Prehensile grasp capability is typically quantified by pinch and grasp forces.
      This work was undertaken to develop a methodology to assess complex, multi-axis
      hand exertions through the measurement of forces and moments exerted by the hand
      along and about three orthogonal axes originating at the grip centre; termed an
      external wrench. Instrumentation consisting of a modified pinch/grip dynamometer
      affixed to a 6 df force cube was developed to simultaneously measure three
      forces, three moments and the pinch/grip force about the centre of the grip.
      Twenty right hand dominant manual workers (10 male and 10 female), free of hand
      or wrist disorders, completed a variety of maximal strength tasks. The randomized
      block design involved three separate grips--power grip, lateral pinch and pulp
      pinch. Randomized within each block were three non-concurrent repetitions of
      isolated maximal force and moment generations along and about the three principle
      orthogonal axes and a maximal grip force exertion. Trials were completed while
      standing, with the arm abducted and elbow flexed to 90 degrees with a wrist
      posture near neutral. Where comparable protocols existed in the literature,
      forces and moments exerted were found to be of similar magnitude to those
      reported previously. Female and male grip strengths on a Jamar dynamometer were
      302.6 N and 450.5 N, respectively. Moment exertions in a power grip (female and
      male) were 4.7 Nm and 8.1 Nm for pronator, 4.9 Nm and 8.0 Nm for supinator, 6.2
      Nm and 10.3 Nm for radial deviator, 7.7 Nm and 13.0 Nm for ulnar deviator, 6.2 Nm
      and 8.2 Nm for extensor, and 7.1 Nm and 9.3 Nm for flexor moments. Correlations
      with and between maximal force and moment exertions were only moderate. This
      paper describes instrumentation that allows comprehensive characterization of
      prehensile force and moment capability.

PMID- 14660218
TI  - Manual lifting load limit equation for adult Indian women workers based on
      physiological criteria.
AB  - A comprehensive equation for the evaluation of a maximum load limit for manual
      load lifting has been developed for the first time for Indian adult female
      workers, based on a physiological criterion due to the limitation of
      applicability of the NIOSH (1991) equation. Ten adult female workers, who had
      been engaged in building construction activities for at least 7 years
      participated in this study. The cut-off value was selected as the working heart
      rate corresponding to the 33% level of maximum aerobic power (i.e. V'O2 max.) of
      this population, which was equivalent to a heart rate of 101.6 beats x min(-1).
      An equation was developed based on the effects of the following three lifting
      parameters on working heart rate: vertical height (knee, waist, shoulder and
      maximum reach height), lifting frequency (1, 4, 7 and 14 lifts x min(-1)), and
      load weight (5, 10 and 15 kg). The variations of the specific lifting parameter
      values were selected from field observations. From this equation, the maximum
      load limit was calculated as 15.4 kg and the workers give this a psychophysical
      rating as in the moderate to heavy category.

PMID- 14660219
TI  - Heat stress while wearing long pants or shorts under firefighting protective
      clothing.
AB  - It was the purpose of this study to examine whether replacing long pants (P) with
      shorts (S) would reduce the heat stress of wearing firefighting protective
      clothing during exercise in a warm environment. Twenty-four Toronto Firefighters
      were allocated to one of four groups that performed heavy (H, 4.8 km x h(-1), 5%
      grade), moderate (M, 4.5 km x h(-1), 2.5% grade), light (L, 4.5 km x h(-1)) or
      very light (VL, 2.5 km x h(-1)) exercise while wearing their full protective
      ensemble and self-contained breathing apparatus. Participants performed a
      familiarization trial followed by two experimental trials at 35 degrees C and 50%
      relative humidity wearing either P or S under their protective overpants.
      Replacing P with S had no impact on the rectal temperature (Tre) or heart rate
      response during heavy or moderate exercise where exposure times were less than 1
      h (40.8 +/- 5.8 and 53.5 +/- 9.2 min for H and M, respectively while wearing P,
      and 43.5 +/- 5.3 and 54.2 +/- 8.4 min, respectively while wearing S). In
      contrast, as exposure times were extended during lighter exercise Tre was reduced
      by as much as 0.4 degrees C after 80 min of exercise while wearing S. Exposure
      times were significantly increased from 65.8 +/- 9.6 and 83.5 +/- 11.6 min during
      L and VL, respectively while wearing P to 73.3 +/- 8.4 and 97.0 +/- 12.5 min,
      respectively while wearing S. It was concluded that replacing P with S under the
      firefighting protective clothing reduced the heat stress associated with wearing
      the protective ensemble and extended exposure times approximately 10 - 15% during
      light exercise. However, during heavier exercise where exposure times were less
      than 1 h replacing P with S was of little benefit.

PMID- 14660220
TI  - Distraction from multiple in-vehicle secondary tasks: vehicle performance and
      mental workload implications.
AB  - This study investigates the impact of multiple in-vehicle information systems on
      the driver. It was undertaken using a high fidelity driving simulator. The
      participants experienced, paced and unpaced single tasks, multiple secondary
      tasks and an equal period of 'normal' driving. Results indicate that the
      interaction with secondary tasks led to significant compensatory speed
      reductions. Multiple secondary tasks were shown to have a detrimental affect on
      vehicle performance with significantly reduced headways and increased brake
      pressure being found. The drivers reported interaction with the multiple in
      vehicle systems to significantly impose more subjective mental workload than
      either a single secondary task or 'normal driving'. The implications of these
      findings and the need to integrate and manage complex in-vehicle information
      systems are discussed.

PMID- 14660221
TI  - No evidence for prolonged latency of saccadic eye movements due to intermittent
      light of a CRT computer screen.
AB  - Despite previous studies it remains unclear, whether saccadic eye movements
      across computer screens may be adversely affected by the intermittency of light
      of cathode ray tubes (CRT). We measured the latency of simple saccades to
      peripheral targets presented on a CRT-screen, operated at refresh rates of 50,
      100 and 150 Hz, compared with a special fluorescent lamp display (FLD). Our
      results suggest that the intermittent light of CRT screens does not prolong the
      latency of saccades not even relative to a control condition of unmodulated
      steady light at the FLD. Further, there was no evidence for any individual effect
      in possibly susceptible subjects, e.g. at high critical flicker frequencies
      (CFF).

PMID- 14660224
TI  - Functional outcomes following anoxic brain injury: a comparison with traumatic
      brain injury.
AB  - PRIMARY OBJECTIVE: To compare the functional outcomes of patients with anoxic
      brain injury (ABI) and patients with traumatic brain injury (TBI) following
      inpatient rehabilitation. RESEARCH DESIGN: Retrospective chart review. METHODS
      AND PROCEDURES: Data on 68 patients with brain injury (34 with ABI and 34 with
      TBI) were collected. MAIN OUTCOMES AND RESULTS: The ABI and TBI groups were
      demographically similar, except that patients with ABI were more likely to be
      married. Both groups significantly improved their function and were similar upon
      discharge. For the ABI group, there were trends toward a shorter length of stay,
      increased total FIM efficiency and decreased cost of stay when compared with the
      TBI group. The patients with ABI tended to be discharged to a sub-acute
      rehabilitation facility more than those in the TBI group. CONCLUSIONS: This study
      is important because it shows that patients with ABI benefit from inpatient
      rehabilitation and made significant functional gains comparable to the gains of
      patients with TBI.

PMID- 14660225
TI  - Psychosocial adjustment and employment outcome 2, 5 and 10 years after TBI.
AB  - OBJECTIVE: A patient's return to work has been considered a good indicator of
      his/her overall adaptation after suffering from TBI. A study has been designed at
      the Hospital del Trabajador to evaluate patients' psycho-pathological and social
      situations and to describe evolution and return-to-work predictors. Particular
      attention was paid to subjects' employment situations 2, 5 and 10 years after
      TBI. METHOD: TBI patients who had also suffered spinal cord injuries, amputations
      and other physical impairments were excluded. A total of 202 individuals were
      evaluated by a psychologist and an occupational therapist during clinical
      interviews using the Hamilton Anxiety and Depression Rating Scale and the
      Neurobehavioural Rating Scale (NRS-R). Work situations were evaluated by
      interviewing the subjects and family members and, whenever possible, a patient's
      immediate supervisor at his or her place of employment. RESULTS: Unemployed
      patients presented more severe symptoms of anxiety and depression than those who
      were working. Significant differences were observed in the NRS-R between employed
      and unemployed patients. There was no change in the marital status for at least
      10 years after TBI. CONCLUSION: Factors determining a poor prognosis for
      adaptation and re-insertion into the workplace are age, a low educational level,
      a lack of job qualifications and greater cognitive impairments. The significant
      differences found between the NRS-R of employed and unemployed patients suggest
      that this variable may be used to predict a subject's ability to return to work.

PMID- 14660226
TI  - Acute confusion following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To determine the incidence, duration and symptoms associated
      with acute confusion/delirium among traumatic brain injury (TBI) neuro
      rehabilitation admissions. RESEARCH DESIGN: Prospective evaluation of
      neurobehavioural impairments following TBI among inpatient neurorehabilitation
      admissions. METHODS AND PROCEDURES: Eighty-five consecutive TBI model system
      patients were evaluated using measures of orientation, cognition, motor
      restlessness and delirium. MAIN OUTCOMES AND RESULTS: Fifty-nine individuals met
      Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition Delirium
      Diagnostic Criteria (DDC) on initial evaluation and 42 of these resolved delirium
      during inpatient rehabilitation. Multivariable logistic regression analyses
      revealed significant unique associations of the Galveston Orientation and Amnesia
      Test (GOAT), Delirium Rating Scale, Cognitive Test for Delirium and time elapsed
      since injury with DDC status. CONCLUSIONS: Findings indicate that delirium is
      common among neuro-rehabilitation admissions with TBI. Use of a single measure
      (e.g. GOAT) will result in poor characterization of the multi-faceted symptom
      complex shown by patients with post-traumatic confusion.

PMID- 14660227
TI  - Measuring the relationship between overt aggression and expectations: a
      methodology for determining clinical outcomes.
AB  - The presence of aggressive behaviour following traumatic brain injury imposes
      special challenges within rehabilitation centres. Survivors of traumatic brain
      injury constitute a heterogeneous population amongst whom problems with increased
      irritability and aggression are characteristic. There is a clear need to
      determine what treatment approaches might be helpful in reducing aggressive
      behaviour. Whilst single-case experimental methodologies including reversal and
      multiple baseline designs seem ideal for this purpose, the compelling need to
      minimize risk can compromise their deployment, especially when aggression takes
      the form of physical assaults on others. When this is the case, there are
      difficulties in assessing whether a change in aggressive behaviour represents a
      successful response to treatment or is simply a function of reduced demand in the
      environment. The contributions made to understanding the relationship between
      aggression and expectations made on patients participating within rehabilitation
      will be explored here. A possible means of quantifying demands using the
      Neurobehavioural Expectations Scale will be described. Three case studies are
      presented that suggest that a methodology that employs concurrent use of this
      tool with the Overt Aggression Scale -- Modified for Neurorehabilitation, can
      enable objective evaluation to be made of the effects of rehabilitation on
      behaviour, without increasing risk.

PMID- 14660228
TI  - Comparison of the Sydney Psychosocial Reintegration Scale (SPRS) with the
      Community Integration Questionnaire (CIQ): psychometric properties.
AB  - PRIMARY OBJECTIVE: This study compared the psychometric properties of two
      community integration measures used with people with acquired brain injury (ABI)
      in the community. RESEARCH DESIGN: Questionnaires were mailed-out to people with
      ABI and nominated proxies. METHODS AND PROCEDURES: Responses were obtained from
      96 people with ABI and 121 proxies on the Community Integration Questionnaire
      (CIQ) and the Sydney Psychosocial Reintegration Scale (SPRS). MAIN OUTCOMES AND
      RESULTS: Matched client-proxy scores were not significantly different. The SPRS
      had greater internal consistency and more normal distributions than the CIQ.
      Correlations between the three pairs of theoretically parallel sub-scales were
      modest (0.41-0.60). Multi-dimensional scaling did not support the theoretical
      structure of the sub-scales, but found two dimensions underpinning the
      measurement of community integration. CONCLUSIONS: Mail-out administration is
      associated with poor completion rates. The SPRS has sound psychometric properties
      when compared to the CIQ. Further research investigating the theoretical
      structure of community integration in ABI is recommended.

PMID- 14660229
TI  - Clinician influences on use of portable electronic memory devices in traumatic
      brain injury rehabilitation.
AB  - PRIMARY OBJECTIVE: To explore the relationship between a group of clinicians' own
      experience, training and confidence with portable electronic memory devices and
      their use of the same in traumatic brain injury (TBI) rehabilitation. RESEARCH
      DESIGN: Survey study. METHODS AND PROCEDURES: Eighty-one TBI clinicians from
      various disciplines and work settings completed a survey distributed in person or
      by mail. MAIN OUTCOMES AND RESULTS: Twenty-nine respondents (36%) reported using
      portable electronic memory devices with patients with TBI. Using regression
      analysis, respondent device training and confidence teaching patients device use
      were statistically associated with respondents' use of such devices in TBI
      rehabilitation. CONCLUSIONS: Portable electronic memory device use with persons
      following TBI may be under-utilized. The importance of ongoing clinician training
      and of maximizing clinician confidence utilizing these devices in TBI
      rehabilitation is emphasized. The representativeness of the respondent sample is
      discussed. Specific training strategies and continued research needs are
      presented.

PMID- 14660230
TI  - Screening for substance abuse in individuals with traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To determine the utility of the CAGE, the Brief Michigan
      Alcohol Screening Test (BMAST) and the Substance Abuse Subtle Screening Inventory
      (SASSI-3) with individuals with traumatic brain injury (TBI), two studies were
      conducted examining the accuracy, sensitivity and specificity of these
      instruments. RESEARCH DESIGN: Data from self-report instruments were compared to
      a clinical interview, Structured Clinical Interview for DSM-IV (SCID), to
      determine the accuracy, sensitivity and specificity. METHODS AND PROCEDURES: Two
      studies were conducted. In study I, 100 individuals with TBI were screened for
      alcohol abuse using the CAGE and the resulting classifications were compared with
      those derived from the SCID. In study II, 223 individuals were screened for
      alcohol abuse and drug abuse using the BMAST and SASSI-3 and the results of these
      screenings were compared with diagnoses obtained by the SCID. MAIN OUTCOMES AND
      RESULTS: The specificity of the self-report instruments was moderately high,
      ranging between 81-83%. The specificity of the CAGE for alcohol abuse both pre-
      and post-TBI was high, 96% and 86%, respectively. The sensitivity of the self
      report instruments was most variable, ranging from 32-95%, with the SASSI face
      valid drug scale and the CAGE alcohol post-TBI indicating the most sensitivity,
      95 and 91%, respectively. CONCLUSIONS: The findings suggest that the CAGE may be
      useful in screening for alcohol abuse and the face valid drug sub-scale of the
      SASSI-3 may be useful in screening for drug abuse in individuals with TBI.

PMID- 14660231
TI  - Epidemiology of acquired brain injury (ABI) in adults: prevalence of long-term
      disabilities and the resulting needs for ongoing care in the region of Flanders,
      Belgium.
AB  - In order to plan services for long-term care of those with acquired brain injury
      (ABI), the prevalence of ABI was investigated by using a postal inquiry sent to a
      representative sample of general practitioners, of whom 121 cooperated and
      registered 186 cases. The corresponding estimated prevalence of adults with ABI
      related disabilities is 183 per 100 000 population. The large majority remained
      at home without professional assistance. One in five had resumed education or
      regained full employment, but over half spent their day at home with no specific
      activity. The need for specific care at home was present in almost half of the
      patients. One-quarter had employment-related needs, and one in five had living
      needs for specialized accommodation or supported living. In conclusion, this
      study primarily revealed unfulfilled needs in the area of day services aiming at
      a maximal social and professional reintegration.

PMID- 14660232
TI  - Misdiagnosing the vegetative state after severe brain injury: the influence of
      medication.
AB  - Patients who suffer severe brain damage may be left unaware of self and of the
      environment and in a permanent vegetative state (PVS). The difficulties in
      correctly ascertaining unawareness after brain injury have been emphasized by a
      number of authors. It is well recognized that toxic-metabolic and drug-induced
      cerebral depression occurs acutely after brain injury. However, less attention
      has been drawn to the effects of medication months after brain injury and the way
      in which medication may confound assessment of awareness and, thus, the reliable
      assessment of long-term prognosis. This paper describes two patients who
      sustained a severe and well-documented structural brain injury, one hypoxic and
      one traumatic. Both were unaware when first seen at 3 months post-injury, but
      both have made useful functional recovery. The paper discusses their progress and
      how the early prescription of large doses of anti-epileptic drugs, sedatives and
      anti-spastic agents in these circumstances may result in an initial misdiagnosis
      of the vegetative state.

PMID- 14660233
TI  - The role of pharmacotherapy in the management of behaviour disorders in traumatic
      brain injury patients.
AB  - The aim of this paper was to systematically review the research published in
      English language on the effectiveness of drugs for the treatment of
      neurobehavioural disorders in patients with traumatic brain injury (TBI). A
      literature search using Medline, Pre-Medline, Embase, Psychlit and Cochrane
      Library databases between 1990 and January 2003 as well as a hand search of Brain
      Injury since 1996 were carried out. Phrases such as 'head injury', 'brain
      injury', 'drug treatment', 'drug trials' and 'randomized controlled trials' were
      used. Sixty-three papers were selected for data synthesis. Of these, 13 were
      randomized controlled trials, eight were prospective observational studies, four
      were retrospective studies, 25 were case series and 13 were single case studies.
      There was a dearth of type I-III evidence. There was no strong evidence either
      way to suggest that drugs are effective in the treatment of behaviour disorders
      in patients with TBI. However, there was weak evidence, primarily based on case
      studies that psychostimulants are effective in the treatment of apathy,
      inattention and slowness; high dose beta-blockers in the treatment of agitation
      and aggression; anti-convulsants and anti-depressants (particularly SSRIs) in the
      treatment of agitation and aggression, particularly in the context of an
      affective disorder; and possibly a specific neuroleptic methotrimeprazine in the
      treatment of agitation in the post-acute stage of Acquired Brain Injury. Some
      drugs that are effective in some patients have been shown to be ineffective in
      others. Some drugs, particularly lithium and dopaminergic drugs could cause
      adverse effects and deterioration in some patients.

PMID- 14660234
TI  - Disturbances in affective communication following brain injury.
AB  - PRIMARY OBJECTIVE: Disturbances in affect expression and perception are often
      clinically observed in brain injured patients during the acute stages of
      recovery. This study examined whether such disturbances are related to the acute
      nature of the injury or specific type of injury in patients with stroke (CVA)
      versus traumatic brain injury (TBI). RESEARCH DESIGN: Retrospective cohort of
      patients seen for inpatient rehabilitation following brain injury. PROCEDURES:
      Participants were 27 CVA and 27 TBI patients. Their performance was compared to
      27 normal controls on the BNI Screen for Higher Cerebral Functions. OUTCOMES AND
      RESULTS: While both patient groups performed significantly worse than the control
      group on affect expression, perception and spontaneity (p<0.01), the CVA group
      performed significantly worse than the TBI group (p<0.01) on affect perception.
      Results of this study document disturbances in affect in brain injured patients
      and highlight the importance of assessing affect during early recovery.

PMID- 14660235
TI  - Functional communication screening in individuals with traumatic brain injury.
AB  - The feasibility of a novel instrument, the Functional Communication Scale (FCS),
      was determined for individuals with moderate-to-mild cognitive-communication
      deficits secondary to traumatic brain injury (TBI). A group design including 30
      adults with confirmed diagnosis and communication problems was utilized.
      Conversational samples with each participant were videotaped and rated for 13 FCS
      items. Three raters with diverse clinical experiences rated the elicited samples.
      Results identified significant and positive relationships between the cognitive
      communication severities and the total FCS scores. Significant inter- and intra
      rater reliability scores were found for the three raters. The FCS also determined
      significant differences between individuals with and without concurrent aphasia
      or dysarthria. No obvious differences were found between males and females nor
      between individuals with the primary diagnosis of TBI vs other neurological
      aetiologies. These findings have implications for assessing the adequacy of
      functional communication of individuals who are candidates for community re
      entry.

PMID- 14660236
TI  - Functional outcome following Botulinum toxin A injection to reduce spastic
      equinus in adults with traumatic brain injury.
AB  - PRIMARY OBJECTIVE: The aim of this study was to assess the effect of Botulinum
      toxin A in the management of spastic equinus resulting from traumatic brain
      injury. RESEARCH DESIGN: A before-after intervention design was used without
      controls. METHODS AND PROCEDURES: Subjects were seven patients suffering from
      traumatic brain injury of average duration 14 (4-38) months as a result of motor
      vehicle trauma, who had spastic equinus interfering with gait. EXPERIMENTAL
      INTERVENTION: The patients were treated with injections of Botulinum toxin A into
      the spastic calf muscles: gastrocnemius, soleus and tibialis posterior.
      Assessments were made pre-injection and at 2 weeks and 3 months post-injection.
      MAIN OUTCOME AND RESULTS: At the end of the 3-month period, all patients showed a
      significant improvement in gait velocity, cadence and stride length. CONCLUSIONS:
      The findings suggest that Botulinum toxin A may be useful in the management of
      spastic equinus following traumatic brain injury.

PMID- 14660237
TI  - Social participation of children and youth with acquired brain injuries
      discharged from inpatient rehabilitation: a follow-up study.
AB  - PRIMARY OBJECTIVE: To determine the nature and extent of participation in home,
      school and community life in children and youth with acquired brain injuries
      (ABI) and identify factors associated with their participation. RESEARCH DESIGN:
      Cross-sectional survey. METHODS AND PROCEDURES: Measures of participation,
      environment and child factors were completed by family caregivers. Data were
      obtained on 60 children and youth with acquired brain injuries up to 6.7 years
      post-discharge from one inpatient rehabilitation programme in the USA.
      Descriptive, correlation and regression analyses were conducted. MAIN OUTCOMES
      AND RESULTS: Children were most restricted in peer social-play, structured
      community activities and managing daily routines. Eighty-two per cent of the
      variance accounted for in participation scores was explained by discharge self
      care and post-discharge child and environmental factor scores. CONCLUSIONS:
      Results suggest that greater efforts are needed to address social participation
      in children and youth with ABI. Information about functional activity at
      discharge and child and environmental factors may provide insight into post
      discharge levels of participation and service needs.

PMID- 14660238
TI  - Through children's eyes: children's experience of living with a parent with an
      acquired brain injury.
AB  - While previous literature on brain injury reports high levels of stress and
      burden in primary caregivers, the impact on children has been overlooked. This
      paper reports on an in-depth, qualitative research project exploring the
      experiences of four children living with fathers with an acquired brain injury
      (ABI). The findings indicate that these children were negatively impacted and at
      risk of emotional and behavioural difficulties. The children reported a
      complexity of feelings associated with the trauma and multiple losses, including
      profound grief, social isolation and fear of family disintegration and violence.
      Despite the difficulties they faced, the children also demonstrated resilience
      and reported positive outcomes such as having greater independence. Although only
      a small pilot study, the current findings highlight the need for both clinicians
      and researchers to be more proactive in questioning their clients and families
      about the level of violence following ABI and that disclosure may be more likely
      to occur with on-going involvement and support. The study concludes that early
      intervention and systemic support is required to minimize the trauma for these
      children. Further research is recommended, not only to replicate these findings
      in a larger sample, but also to explore in-depth children's experience of living
      with a parent with a brain injury.

PMID- 14660239
TI  - Time interval of oral feeding recovery as a prognostic factor in severe traumatic
      brain injury.
AB  - PRIMARY OBJECTIVES: To assess the outcome of severe traumatic brain injury at
      least 1 year after trauma, in relation to some early clinical prognostic factors
      occurring during coma recovery. RESEARCH DESIGN: Retrospective study conducted at
      the post-coma unit of a rehabilitation hospital. METHODS AND PROCEDURES: A total
      of 43 patients were included. All of the patients sustained severe traumatic
      brain injury and prolonged coma, i.e. coma lasting at least 15 days. Outcome was
      assessed by means of Glasgow Coma Scale, Barthel Index and Mini Mental State 1
      year after trauma, in relation to some early clinical prognostic factors
      occurring during coma recovery. MAIN OUTCOMES AND RESULTS: At the 1 year follow
      up, a statistically significant correlation was found with both the Glasgow
      Outcome Scale and the Barthel Index for the time interval from brain injury to
      recovery of the following clinical variables: optical fixation, ability to obey
      commands, spontaneous motor activity and first safe oral feeding. Psychomotor
      agitation and bulimia were also favourable prognostic factors for the final
      outcome. CONCLUSIONS: In the present study, first safe oral feeding during coma
      recovery represents the clinical feature that better predicts the final outcome
      of patients with severe traumatic brain injury and prolonged coma.

PMID- 14660241
TI  - The emerging epidemic of cardiovascular disease.

PMID- 14660242
TI  - The events registration and survey procedures in the Northern Sweden MONICA
      Project.
AB  - INTRODUCTION: The WHO MONICA Project (Multinational Monitoring of Trends and
      Determinants in Cardiovascular Disease) was initiated in 1982. The purpose was to
      evaluate to what extent mortality trends could be explained by changes over time
      in the population load of conventional cardiovascular risk factors. To test this
      hypothesis, time trends in cardiovascular event rates have been correlated with
      trends in levels of risk factors in 35- to 64-year-old men and women in 38
      populations. In most MONICA populations, the study has covered a period of 10
      years or more. METHODS: All acute myocardial infarction and stroke events have
      been registered in a population-based setting in Norrbotten and Vasterbotten
      counties from 1985 and onwards. The total population is approximately 510000
      inhabitants. In the frame of the WHO MONICA Project, the same strict criteria
      have been used in all years. Another part of the MONICA Project is population
      risk factor surveys. In Northern Sweden the first survey took place in 1986 and
      the following surveys were performed in 1990, 1994, and 1999, including the age
      group 25-74 years (the first two surveys were of the age range 25-64 years).
      RESULTS: From 1985 to 2000, in total 18105 suspected stroke events, aged 25-74
      years, were scrutinized and validated at the central stroke office in Northern
      Sweden. Of these, 13908 were found to fulfil the MONICA criteria of an acute
      stroke. During the period 1985 to 1998, in total 13228 cases of suspected acute
      myocardial infarction, aged 25-64 years, were registered. Of these, 8744
      fulfilled the MONICA criteria for acute myocardial infarction. In the four
      surveys, in total 9000 randomly selected men and women were invited for survey.
      Of these 6952 (77%) participated in the surveys. CONCLUSION: From 1985 and
      onwards, the WHO MONICA project has been going on in Northern Sweden. During the
      whole time the same strict WHO criteria have been followed.

PMID- 14660244
TI  - MONICA quality assessments.
AB  - The authors give an overview of the quality assessments in the WHO MONICA project
      and compare the quality of the data from Northern Sweden with other reporting
      units. METHODS AND RESULTS: Standardized measurement procedures and routine
      checks were used to ensure good quality of the data. The quality has been
      evaluated by a scoring system. The results show that the data from Northern
      Sweden have good quality for all variables except total cholesterol in the
      initial survey. In the subsequent surveys, the quality of cholesterol data was
      good. CONCLUSIONS: Great effort was put in to ensure good data quality and
      Northern Sweden is one of the MONICA units with very good quality of data.

PMID- 14660243
TI  - Cardiovascular disease and diabetes in the Northern Sweden Health and Disease
      Study Cohort - evaluation of risk factors and their interactions.
AB  - The purpose of this paper is, first, to describe the organization, sampling
      procedures, availability of samples/database, ethical considerations, and quality
      control program of the Northern Sweden Health and Disease Study Cohort. Secondly,
      some examples are given of studies on cardiovascular disease and diabetes with a
      focus on the biomarker programme. The cohort has been positioned as a national
      and international resource for scientific research.

PMID- 14660245
TI  - Trends in lifestyle 1986-99 in a 25- to 64-year-old population of the Northern
      Sweden MONICA project.
AB  - AIMS: The authors explore the time trends in lifestyle factors in the Northern
      Sweden MONICA population, including physical activity, intake of certain foods,
      coffee and alcohol consumption, smoking, and the use of smokeless tobacco.
      METHODS: Four health surveys during a 14-year time span were compared (1986,
      1990, 1994, and 1999). The participation rate in all surveys was high. A
      questionnaire with similar or comparable questions about lifestyle factors was
      used across all health surveys. RESULTS: A large variation was demonstrated in
      the consumption of saturated fat in dairy products across the surveys. The use of
      butter on bread and of 3% fat milk clearly declined in favour of using low-fat
      margarine and 1-1.5% fat milk. A decline in the intake of boiled or baked
      potatoes together with an increase in the intake of pasta and rice was
      demonstrated. There were no changes in leisure-time physical activity. The
      proportion of the population using tobacco was unaltered. In men, smoking
      declined during the period but simultaneously there was an increase in the use of
      smokeless tobacco. The use of "boiled" or Scandinavian coffee diminished and more
      frequent use of alcohol was seen, especially in men. CONCLUSION: Pronounced
      changes were seen in food consumption with a decrease in saturated fat intake,
      boiled coffee, and potatoes and an increase in alcohol, rice, and pasta
      consumption. No clear time trends were found in physical activity or in the use
      of tobacco.

PMID- 14660246
TI  - Psychosocial factors in the Northern Sweden MONICA project.

PMID- 14660247
TI  - Trends in blood pressure, lipids, lipoproteins and glucose metabolism in the
      Northern Sweden MONICA project 1986-99.
AB  - AIM: The authors present an analysis of time trends in blood pressure,
      hypertension, and lipids in the adult population of Northern Sweden over the
      period 1986-99. METHOD: Four population surveys were undertaken with new and
      independent cohorts, 25-64 years old. RESULTS: Small changes in blood pressure
      were observed during the study period with increased systolic blood pressure in
      men and decreased diastolic blood pressure in women. The proportion with high
      blood pressure was found to be constant over time and only 50% were prescribed
      antihypertensive drugs and of these only a minority were normotensive. Total
      serum cholesterol decreased from 6.4 to 5.7 mmol/l in men and from 6.3 to 5.7
      mmol/l in women over the study period, and this was accompanied by an increase in
      HDL cholesterol by about 10% in both sexes. The proportion with high cholesterol
      decreased from 41% to 26%. Triglycerides increased between 1986 and 1990 and no
      further changes were found in the following surveys. CONCLUSION: In the Northern
      Sweden MONICA population total cholesterol has declined and HDL cholesterol has
      increased during the past 13 years and small changes in blood pressure have been
      observed for both men and women.

PMID- 14660248
TI  - Trends in event rates of first and recurrent, fatal and non-fatal acute
      myocardial infarction, and 28-day case fatality in the Northern Sweden MONICA
      area 1985-98.
AB  - AIMS: This study looks at trends in event rates of first and recurrent fatal and
      non-fatal acute myocardial infarction (AMI), and 28-day case fatality in AMI
      within the Northern Sweden MONICA area. METHODS: The AMI event rate and 28-day
      case fatality in acute myocardial infarction were registered between 1985 and
      1998 in the two northernmost counties in Sweden in men and women in the age
      groups 25-64 years. RESULTS: Statistically significant mean annual decreases were
      found in fatal and non-fatal combined event rates (4% for men and 2.3% for
      women), fatal event rate (7.1% for men and 5% for women), fatal first acute
      myocardial infarction (7.1% for men and 4.4% for women), and both non-fatal and
      fatal recurrent AMI for both sexes (5.5% for both men and women for non-fatal
      and, for fatal AMI, 7.1% for men and 5.7% for women). In addition, there were
      significant decreases for men in non-fatal event rate (2.4%), and non-fatal first
      AMI (1.4%). The decreases in case fatality were small, especially so for women.
      CONCLUSIONS: There is a trend of decreasing event rates in both fatal and non
      fatal AMI, and first and recurrent AMI, most pronounced for men. The case
      fatality also decreased although to a lesser degree, suggesting that the
      decreasing mortality in ischaemic heart disease mainly is caused by reduced
      disease incidence.

PMID- 14660249
TI  - Stroke in Northern Sweden.
AB  - BACKGROUND: Stroke is one of the most common causes of death and long-term
      disability worldwide. Although stroke mortality has decreased in most
      industrialized countries, there are populations, particularly in East Europe, in
      which the mortality has increased. The WHO initiated, 20 years ago, the MONICA
      Project. The aim of the study was to measure trends in coronary heart disease and
      stroke and to assess the extent to which these were related to changes in known
      risk factors. DESIGN: The Northern Sweden MONICA stroke study started in 1985 and
      is still ongoing. All individuals with an acute stroke in the age group 25-74
      years have been included in the stroke register. Death certificates, discharge
      records, and GPs' records are screened and validated using strict MONICA
      criteria. RESULTS: Stroke event rates (first ever and recurrent stroke) per
      100000 and year in the age group 25-74 years varied little over the years.
      Between 1985 and 1998 the annual incidence varied between 318 and 372 in men and
      between 195 and 240 in women, with no secular trends at all. The 28-day case
      fatality decreased in both men and women, from 19% to 11%. Logistic regression
      analyses showed a risk reduction in dying from stroke to 0.55 (p<0.0001) the last
      year compared with the first, with an absolute annual reduction in case fatality
      of 3%, in both men and women. In international comparison Northern Sweden shows
      an intermediately high incidence and one of the lowest case fatality rates of all
      participating populations. The incidence in subarachnoid haemorrhage was among
      the highest. CONCLUSION: The ongoing decline in stroke mortality in Sweden is
      driven exclusively by declining case fatality, whereas event rates (first ever
      and recurrent stroke) have remained the same since 1985. This, together with more
      people entering advanced, stroke-prone age groups, implies that the burden of
      stroke will continue to increase in Sweden.

PMID- 14660250
TI  - Diabetes and obesity in Northern Sweden: occurrence and risk factors for stroke
      and myocardial infarction.
AB  - AIMS: The authors describe the occurrence of diabetes and obesity in the
      population of Northern Sweden and the role of diabetes in cardiovascular disease.
      METHODS: Four surveys of the population aged 25 to 64 years were undertaken
      during a 14-year time span. Stroke events in subjects 35-74 years during 1985-92
      and myocardial infarction in subjects 25-64 years 1989-93 were registered.
      RESULTS: The prevalence of diagnosed diabetes was 3.1 and 2.0% in men and women,
      respectively, and 2.6 and 2.7% for previously undiagnosed diabetes. During the 13
      year observation period, BMI increased 0.96 kg/m(2) in men and 0.87 in women. The
      proportion of subjects with obesity (BMI>or=30) increased from 10.3% to 14.6% in
      men and from 12.5% to 15.7% in women. Hip circumference increased substantially
      more than waist circumference, leading to a decreasing waits-to-hip ratio (WHR).
      The relative risk for stroke or myocardial infarction was four to six times
      higher in a person with diabetes than in those without diabetes. The 28-day case
      fatality for myocardial infarction, but not for stroke, was significantly higher
      in both men and women with diabetes. Population-attributable risk for diabetes
      and stroke was 18% in men and 22% in women and for myocardial infarction it was
      11% in men and 17% in women. CONCLUSION: Obesity is becoming more common,
      although of a more distal than central distribution. The burden of diabetes in
      cardiovascular diseases in Northern Sweden is high.

PMID- 14660251
TI  - The Northern Sweden MONICA project: concluding remarks.

PMID- 14660252
TI  - The Northern Sweden MONICA Project. Bibliography.

PMID- 14660253
TI  - Inequality/difference in education: is a real explanation of primary and
      secondary effects possible?
AB  - The persistence of social disparities in educational achievement in contemporary
      societies is a matter of concern to social theory. Sociology of education has
      distinguished between the primary and secondary effects of socialization in order
      to construct explanatory theories of inequality of educational opportunity.
      Empirical evidence from the recent OECD PISA research is analysed to suggest that
      causes of the primary effect are the most important. The case is made with close
      reference to Goldthorpe's attempt to provide a rational action model of social
      disparities in education. An approach informed by scientific realism is held to
      offer a more adequate explanation.

PMID- 14660254
TI  - Declining inequality? The changing impact of socio-economic background and
      ability on education in Australia.
AB  - The paper addresses several debates surrounding the reproduction of socio
      economic inequality: (i) the persistent inequality thesis, which maintains that
      despite the increases in educational participation socio-economic inequalities in
      education have not declined; (ii) the related thesis of maximally maintained
      inequality, which proposes that socio-economic inequalities decline only when
      participation levels for the most privileged socio-economic group approach
      saturation levels; (iii) the meritocracy debate on the importance of ability vis
      a-vis socio-economic background and changes in its influence over time; and (iv)
      the effect of policy changes on socio-economic inequalities in education. These
      issues are addressed using data from six Australian youth cohorts born between
      1961 and the mid-1980s.

PMID- 14660255
TI  - Educational homogamy in Ireland and Britain: trends and patterns.
AB  - This paper examines the pattern of educational homogamy in Ireland and Britain.
      Using contemporary data on recent marriages from the early 1970s through to the
      mid-1990s, we show that these two countries share a broadly similar pattern of
      educational homogamy, which is quasi-symmetric in character, with no tendency for
      women to marry up over and above that which can be attributed to the gender
      difference in educational attainment. In the 1970s, the strength of homogamy was
      much weaker in Ireland than in Britain. But we discern a clear inter-country
      difference in how the net strength of homogamy has changed over time. While it
      has declined in Britain since the 1970s, in Ireland the strength of homogamy has
      first increased and then levelled off. Our findings are inconsistent with the
      inverted U-shaped relationship between economic development and homogamy reported
      by Smits, Ultee and Lammers (1998) - an argument premised on secular change in
      the criteria of spouse selection. Instead, our results are better understood in
      terms of Mare's (1991) life course argument that homogamy is inversely related to
      the time-gap between school departure and first marriage.

PMID- 14660256
TI  - Social capital and social exclusion in England and Wales (1972-1999).
AB  - Recent research on social capital has explored trends in membership in voluntary
      organizations. However, there is currently little robust evidence on such trends
      in the UK since the 1970s, nor is there any analysis of whether participation
      bridges social divisions or accentuates them. This paper explores trends in
      participation in England and Wales since 1972 using data from the Social Mobility
      Inquiry of 1972 and the British Household Panel Survey of 1992 and 1999. We are
      concerned with social exclusion mechanisms in social capital generation in
      Britain over the three decades. Using binomial and multinomial models to 'unpack'
      the effects of socio-cultural factors on civic participation and on different
      types of associational membership, we test the thesis of across-the-board decline
      in social capital by Putnam (2000) and that of rising levels of middle-class
      social capital versus consistent low levels of working-class social capital by
      Hall (1999). The results show significant socio-cultural-gender differences, a
      relative stability of middle-class participation, and a rapid decline in the
      working-class access to social capital. We challenge the established accounts of
      both theses.

PMID- 14660257
TI  - Signs of change in Turkey's working class: workers' age-related perceptions in
      the modern manufacturing sector.
AB  - This paper explores the possible effects of the increasing exposure to modernity
      on younger workers in some sectors of developing countries with special reference
      to those employed in advanced manufacturing in Turkey. In recent decades Turkey
      has undergone considerable urbanization, improvements in literacy and rising
      levels of formal education. The paper systematically examines differences in the
      work-related attitudes and expectations, commitment and aspirations of younger
      and older workers, who have been exposed to these processes to different degrees.
      It is broadly confirmed that younger workers have higher expectations and
      aspirations that make them relatively less satisfied with a number of aspects of
      their work and which are likely to make for a less committed more critical
      workforce.

PMID- 14660258
TI  - Rethinking the concept of professionalism: the case of journalism.
AB  - Journalists in the UK have always been ambivalent about what form of occupational
      control to pursue. Although resistant to the structures of the conventional
      profession, they have embraced the idea of 'professionalism'. As the formations
      traditionally associated with Anglo-American professions become relevant to fewer
      and fewer employees and increasingly subject to external regulation it is more
      relevant, we suggest, to investigate how the discourse of 'professionalism' as a
      set of values and identities can be mobilized by employers as a form of self
      discipline. Journalism, notable for its powerful occupational mythology, provides
      a vivid example of how this process has eased the imposition of radical changes
      to the organization of work. Now, ironically, recent changes in the occupation's
      social composition and training may mean that journalists, who have always
      cherished a self-image as socially marginal, will aspire to conventional
      professional respectability.

PMID- 14660259
TI  - Interdependencies, values and the reshaping of difference: gender and generation
      at the birth of twentieth-century modernity.
AB  - The paper explores the mutuality of values, claims and social relations in the
      process of social change. Values are not separable from social relations but are
      embedded in the shaping and reshaping of social difference and interdependence.
      The paper focuses on developments around the turn of the twentieth century, and
      analyses changes in the relative social positioning of children and adults, and
      women and men, shifting patterns of interdependence, and linked values and ideas
      about difference. The reconfiguring of generational and gender relations was
      integral to the first fertility decline, to transformation in family life and
      societal divisions of labour, and to the embedding of particular values and
      claims regarding gendered difference, identities and gender appropriate roles.
      Analysis of these developments reveals the mutuality of 'cultural' and 'material'
      processes and holds lessons for interpreting social change today.

PMID- 14660260
TI  - Choice and constraints in mothers' employment careers: McRae replies to Hakim.

PMID- 14660262
TI  - Modest innovations in psoriasis treatment?

PMID- 14660263
TI  - Potassium iodide remains the most effective therapy for cutaneous sporotrichosis.
AB  - Sporotrichosis is a subcutaneous fungal infection caused by the dimorphic fungus
      Sporothrix schenckii. Itraconazole has largely replaced older therapies, but we
      present a case of lymphocutaneous sporotrichosis that failed to respond to an
      adequate course of itraconazole yet responded dramatically to treatment with
      saturated solution of potassium iodide (SSKI).

PMID- 14660264
TI  - Mycophenolate in dermatology.
AB  - Originally used to treat psoriasis nearly three decades ago, mycophenolic acid,
      reformulated as mycophenolate mofetil (MMF), has been rediscovered by the world
      of dermatology. As a relatively well-tolerated immunosuppressive used in organ
      transplant recipients, MMF has recently been reported to show promise for several
      dermatologic conditions, including psoriasis, pemphigus vulgaris, pyoderma
      gangrenosum, bullous lichen planus, and even connective tissue diseases such as
      lupus erythematosus and dermatomyositis. Although not intended to be exhaustive,
      this review discusses MMF with regard to its basic pharmacology, its side
      effects, and its reported efficacy in a variety of dermatologic indications.
      Relevant literature was retrieved by a Medline search combining the terms
      "mycophenolate" or "mycophenolic acid" and "skin" or "skin disease" or a number
      of specific conditions ("psoriasis", "dermatitis", "eczema", "pemphigoid",
      "pemphigus", "vasculitis", "pyoderma gangrenosum", "Crohn's disease", "graft
      versus-host disease", "lichen planus"). As MMF has only been recently re
      introduced for dermatologic application, the nature of much of the literature is
      admittedly that of case reports or case series. Nevertheless, the results are
      sufficiently promising to warrant further larger, control studies.

PMID- 14660265
TI  - Successful treatment of dandruff with 1.5% ciclopirox olamine shampoo in Korea.
AB  - BACKGROUND: Dandruff is a chronic scalp condition characterized by scaling. The
      common causative agent is now accepted to be the lipophilic yeast Malassezia
      furfur. Ketoconazole, a highly effective antifungal agent against M. furfur has
      been used for the treatment of dandruff. AIM: To determine whether a 1.5%
      ciclopirox olamine shampoo is as effective as a 2% ketoconazole shampoo for the
      treatment of mild to moderate dandruff. METHODS: A total of 64 patients, with
      mild to moderate dandruff, participated in the study. The study consisted of
      three consecutive phases: a 2-week washout period, a 4-week treatment period and
      a 2-week post-treatment period. Patients were randomized equally to either the
      1.5% ciclopirox olamine shampoo or 2% ketoconazole shampoo. An overall dandruff
      score was calculated using an area of dandruff involvement score and a severity
      score. Patients evaluated the presence of pruritus and also reported a global
      evaluation of efficacy. RESULTS: In all, 57 patients successfully completed all
      three phases. The overall dandruff score declined progressively throughout the
      treatment period for both shampoos. A slight increase in pruritus was observed in
      the ciclopirox olamine treatment group during the post-treatment phase. Regarding
      global self-assessment of efficacy, both treatment groups were pleased with their
      scalp condition following treatment. CONCLUSION: Ciclopirox olamine shampoo
      appears to offer an effective, safe and easy to use treatment for mild to
      moderate dandruff.

PMID- 14660266
TI  - Retrospective survey of serum lipids in patients receiving more than three
      courses of isotretinoin.
AB  - Isotretinoin is well recognised to cause hyperlipidaemia. This is most obvious
      during the second month of a 4-month course. Since there are no long-term data on
      lipid profiles, we have identified 30 subjects who have received 3 or more
      courses of isotretinoin. They had been exposed to a median of 24.5 months (range
      12-103) isotretinoin therapy with a median total cumulative dose of 350 mg/kg
      (range 152-1221). The median serum cholesterol pre-treatment was 4.6 mmol/L
      (range 3-6.4). This compared to a median of 4.5 mmol/L (range 3-6.4) just prior
      to starting the final course. The median triglyceride levels before treatment and
      pre-final course were 0.8 mmol/L (range 0.3-1.7) and 0.92 mmol/L (range 0.4-2.6)
      respectively, indicating no significant change in cholesterol or triglyceride
      concentrations when measured prior to the first and last courses. In addition
      there was no correlation between cholesterol or triglyceride concentration before
      the final course of isotretinoin and the total cumulative dose of isotretinoin.
      We conclude that there appears to be little risk of causing hyperlipidaemia by
      prolonged therapy with isotretinoin in patients with acne.

PMID- 14660267
TI  - Topical calcipotriol ointment in the treatment of morphea.
AB  - A 5-year-old girl presented with a 2-month history of an indurated hypopigmented,
      atrophic plaque of biopsy-documented morphea over the right hip area. Previous
      treatment with 0,1% betamethasone valerate cream twice a day for 3 months failed
      to improve the lesion. She was treated with calcipotriol ointment twice daily,
      with nightly occlusion to the plaque for 9 months, and this resulted in
      resolution. No side effects were noted.

PMID- 14660268
TI  - Erythrodermic, recalcitrant psoriasis: clinical resolution with infliximab.
AB  - This report describes the case of a patient with erythrodermic psoriasis who had
      failed all previous therapies and been hospitalized numerous times over a 12-year
      period that responded dramatically to treatment with infliximab. The potential
      utility of infliximab as a therapeutic alternative for erythrodermic psoriasis is
      discussed.

PMID- 14660269
TI  - Successful treatment of recalcitrant psoriasis with a combination of infliximab
      and hydroxyurea.
AB  - We report the use of a combination of the tumour necrosis factor alpha (TNF
      alpha) inhibitor infliximab and hydroxyurea to achieve control of disabling
      psoriasis and psoriatic arthritis. Our patient had psoriasis that proved
      resistant to conventional therapy including vitamin D analogues, topical
      steroids, dithranol, crude coal tar, narrow band UVB, bath PUVA and acitretin.
      She subsequently responded to hydroxyurea 1 g daily combined with infliximab
      infusions repeated at three monthly intervals which led to satisfactory control
      of her psoriasis and psoriatic arthritis. She has not reported any side-effects
      from this treatment regimen and her full blood count has remained normal.

PMID- 14660270
TI  - Etanercept therapy in patients with autoimmunity and hepatitis C.
AB  - Accumulated data suggest that etanercept may be a therapeutic option in patients
      with hepatitis C and coexisting autoimmune disorders such as rheumatoid
      arthritis, psoriasis, psoriatic arthritis and ankylosing spondylitis.
      Additionally, etanercept may actually be of benefit, when used in combination
      with standard treatments, for hepatitis C.

PMID- 14660271
TI  - An open label evaluation of the efficacy of imiquimod 5% cream in the treatment
      of recalcitrant subungual and periungual cutaneous warts.
AB  - BACKGROUND: Periungual and subungual warts are very difficult to eradicate with
      current therapies. Most are destructive in nature (liquid nitrogen, cantharidin,
      vascular lesion laser) and inflammation, pain and pigment dyschromia are common
      side effects. Furthermore, failure to respond or appearance of new lesions often
      leads to even more destructive treatments (CO(2) laser, excisional surgery) and
      can lead to more pain and scarring. METHODS: In an open trial, the efficacy,
      safety, and tolerability of topical imiquimod 5% cream was assessed in 15
      patients with resistant and recurrent periungual and subungual warts over a 16
      week period. RESULTS: Twelve patients (80%) completed therapy, showing complete
      resolution after a mean time of three weeks (range 1-6 weeks), with the remaining
      three patients (20%) being classified as non-responders. Local side effects
      (erythema, pruritus, burning and pain) were generally mild and well-tolerated. No
      relapses occurred during a 6-month follow-up. CONCLUSION: Topical imiquimod is an
      interesting novel treatment for multiple periungual and subungual warts.
      Tolerability is excellent when compared to other commonly used modalities and
      there are few side effects. This trial suggests a high clinical response rate.
      This treatment is applicable to patients who have failed conventional therapies
      before embarking on potentially scarring approaches such as excisional surgery.

PMID- 14660272
TI  - An independent comparison of terbinafine and itraconazole in the treatment of
      toenail onychomycosis.
AB  - BACKGROUND: Previously, sponsored publications have shown that either terbinafine
      or itraconazole (pulse regimen) are effective for patients with toenail
      onychomycosis. However, independent comparative studies are lacking. OBJECTIVES:
      To objectively compare treatment with terbinafine and itraconazole in patients
      with toenail onychomycosis. METHODS: The effectiveness of terbinafine (250 mg/day
      3 months) versus itraconazole pulse regimen (400 mg/day for the first week of
      each month, for three cycles) was retrospectively evaluated in patients with
      toenail onychomycosis using mycological tests and subjective outcome measures.
      Statistical analyses were performed using one-way analyses of variance (ANOVA)
      for continuous variables and Fisher exact tests for categorical variables.
      RESULTS: Included in the study were 117 patients (74 patients treated by
      terbinafine and 43 patients treated with itraconazole). Patients were examined at
      an average period of 20 months after the end of therapy. Mycological cure was
      observed in 70.6% and 62.8% of the patients who were treated by terbinafine or
      itraconazole, respectively (not statistically significant). Mean visual analogue
      scale assessment of treatment outcome was 79.9 mm (SD 24.7 mm) and 65.2 mm (SD
      34.6 mm) for patients treated by terbinafine or itraconazole, respectively
      (p=0.008). When the results were stratified according to age and gender, it was
      observed that the advantage of terbinafine versus itraconazole retained
      statistical significance only for patients who were 55 years old and above, or
      females. CONCLUSIONS: Mycological cure proportions were not statistically
      significant between patients treated by terbinafine or itraconazole for toenail
      onychomycosis. However, better subjective outcome measures indicated an advantage
      for terbinafine over itraconazole, noticeable in females and patients 55 years
      old and above.

PMID- 14660273
TI  - Comparative study on a single treatment response to long pulse Nd:YAG lasers and
      intense pulse light therapy for hair removal on skin type IV to VI--is longer
      wavelengths lasers preferred over shorter wavelengths lights for assisted hair
      removal.
AB  - OBJECTIVE: To investigate the safety and effectiveness of a long pulsed Nd:YAG
      (1064nm) laser compared to a shorter wavelength intense pulse light system for
      assisted hair removal in volunteers with skin type 1V, V and VI. METHODS: Eleven
      patients of Fitzpatrick skin type IV-VI were recruited into the study. The area
      treated included the face (upper lips, chin and jaw area), axillae and legs. One
      half of the body was treated with the long pulse Nd:YAG laser and the other half
      was treated with the IPL system randomly under topical anesthesia. Degree of pain
      experienced during treatment, the treatment outcome and any complications were
      observed. Patients were reviewed at 2 weeks and 6 weeks post-treatment. RESULTS:
      Volunteers generally described pain from the IPL system as "prolonged burning
      sensation" but tolerable. Pain from Nd:YAG laser treatment was described as
      "pinprick" and more intense but tolerable. "Slowing of hair growth"was reported
      with IPL and Nd:YAG, but with a greater effect from Nd:YAG. Sixty-four percent
      and 73%(8/11) noticed hair reduction <20% after 6 weeks on IPL and Nd:YAG treated
      side respectively (ns). Post-inflammatory pigmentation occurred in some
      volunteers on the IPL treated sides whereas this was not seen on any Nd:YAG
      treated side, and three of these patients experienced blistering, followed by
      post-inflammatory pigmentation. CONCLUSION: In our experience the long pulse
      width 1064 nm Nd:YAG laser, which can penetrate 5-7 mm into the dermis depths to
      reach the whole length of the hair follicle, would be expected to produce
      sufficient follicular injury with less epidermal damage in patients with darker
      skin type compared to shorter wavelength laser and light system.

PMID- 14660274
TI  - Silicone gel sheets relieve pain and pruritus with clinical improvement of
      keloid: possible target of mast cells.
AB  - Silicone gel sheet treatment is widely used to treat hypertrophic scars and
      keloids since it is easily applied and prevents scar pain and itching. We used
      Cica-Care silicone gel sheets in the conservative treatment of six patients for
      24 weeks and recorded pain, itching, redness, and scar elevation every 4 weeks.
      We also investigated the number of mast cells and Fas antigen expression in the
      lesional skin (one patient) before and after treatment. The pain and itching
      clearly decreased after 4 weeks of the silicone gel sheeting and disappeared
      after 12 weeks. Twelve weeks were required for a reduction in scar redness and
      elevation. After 24 weeks, a decrease in the number of mast cells and the
      enhanced expression of Fas antigen by lesional fibroblasts were observed. Thus,
      silicone gel sheeting is effective and safe, especially with more severe symptoms
      of pain and itching possibly induced by mediators derived from increased mast
      cells.

PMID- 14660275
TI  - CO2 laser therapy for Milia en plaque.

PMID- 14660276
TI  - Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene, encoding
      for the membrane transporter MRP6, whose physiological role is still unknown. PXE
      is characterized by skin, eye, and cardiovascular alterations mainly due to
      mineralization of elastic fibers. The ultrastructural alterations of a large
      number of tissues obtained at autopsy from 2 PXE patients were analyzed and
      compared to clarify the involvement of the various organs in PXE and to identify
      cell types responsible for clinical manifestations. Ultrastructural alterations
      typical of PXE were present in all organs examined and consisted mostly of
      fragmentation and mineralization of a number of elastic fibers, abnormalities of
      collagen fibril shape and size, and, less frequently, deposition of aggregates of
      matrix constituents in the extracellular space. The severity of alterations was
      more pronounced in the organs affected by the clinical manifestations of PXE.
      Interestingly, veins and arteries were similarly damaged, the adventitia and the
      perivascular connective tissue being the most affected areas. Therefore,
      alterations in PXE are systemic and affect all soft connective tissues, even in
      the absence of specific clinical manifestations. The localization of alterations
      suggests that fibroblasts and/or smooth muscle cells are very likely involved in
      the pathogenesis of the disorder. These findings may help in the diagnosis of PXE
      when clinical manifestations affect internal organs.

PMID- 14660277
TI  - Cytochemical and ultrastructural changes in the osteoclast-like giant cells of
      giant cell tumor of bone following bisphosphonate administration.
AB  - Giant cell tumor of bone (GCT) is a local aggressive neoplasm of bone
      characterized by expansive osteolytic lesions at the epiphysis of long bones.
      Bisphosphonates have been used to prevent bone resorption in secondary osteolytic
      tumors because of their strong anti-osteoclastic action. The authors studied the
      apoptosis and ultrastructural changes induced in osteoclast-like giant cells of
      GCT, following treatment with the aminobisphosphonate pamidronate in 16 patients
      with GCT of bone. Transmission electron microscopy (TEM) was used to identify
      ultrastructural changes, indicative of apoptosis, in the cytoplasm and the
      nucleus of the giant cells. Significant changes were observed in tumor samples
      from all 16 patients. In the cytoplasm these changes were characterized by
      abundant large tubular vesicles containing a central electrodense core scattered
      through the cytoplasm. In addition, mitochondria in the sections from pamidronate
      treated patients appeared to be edematous when compared with sections from
      untreated patients. Nuclear changes in the giants cells were characterized by the
      formation of dense chromatin material scattered throughout the nucleus. The TUNEL
      labeling assay indicated that the mean pretreatment apoptotic index of 7.8%
      increased to 53% following pamidronate treatment. This was statistically
      significant (p<.001) and correlated well with the ultrastructural changes noted
      on TEM. The formation of abundant tubular vesicles in giant cells following
      bisphosphonate treatment may reflect disturbed vesicular trafficking and may
      affect the bone resorbing activity of giant cells.

PMID- 14660278
TI  - Ultrastructural immunostaining of infiltrating ductal breast carcinomas with the
      monoclonal antibody H: a comparative study with cytokeratin 8.
AB  - The monoclonal antibody H (mAbH) detects an epitope consisting of an O-linked N
      acetyl glucosamine (O-GlcNAc) and neighboring amino acids. This epitope has been
      found by using extracts from the MCF-7 human breast carcinoma cell line in
      immunoblotting experiments, on cytokeratin 8 (CK8) and 5 other polypeptides. In
      the present study, a double immunogold method was applied for the colocalization
      of CK8 and mAbH epitope on epoxy thin sections in 18 cases of infiltrating ductal
      breast carcinomas (IDBC) and in 6 cases of fibroadenomas, to study the accurate
      subcellular distribution of CK8 in breast cancer cells, as compared to the 5
      polypeptides, recognized by mAbH. Furthermore, a detailed quantitative evaluation
      of the double immunolocalization over the cellular compartments of cancer cells
      was undertaken with the aid of a computerized image analysis system and the
      results were assessed statistically. The distribution pattern of CK8 and the mAbH
      epitope in the neoplastic mammary epithelial cells was similar in IDBC as
      compared to fibroadenomas, while the gold labeling intensity of these epitopes
      differed over the cellular compartments between malignant and benign biopsies.
      The results reveal the significance of the role of CK8 and O-GlcNAc glycosylation
      in the biology of the neoplastic mammary cells in vivo, determining their
      malignant potential.

PMID- 14660279
TI  - A simplified method for measuring the thickness of glomerular basement membranes.
AB  - Measurement of the thickness of glomerular basement membranes is required for the
      diagnosis of thin membrane nephropathy. Over the years various morphometric
      methods have been used but some are laborious so there is a need for establishing
      a simplified method for measuring thickness. In the present study 20 renal
      biopsies were used to carry out a comparative morphometric analysis between 2
      methods. The first method was based on measuring thickness at the maximum number
      of available points, whereas for the second method, thickness was measured at
      only 5 points per loop. Since both methods gave mean values that are not
      statistically different in each patient, the authors recommend that the
      simplified method be used routinely for diagnosis.

PMID- 14660280
TI  - 5'-CpG island methylation of the FHIT gene is associated with reduced protein
      expression and higher clinical stage in cervical carcinomas.
AB  - Aberrant transcription of the FHIT gene has been observed in many solid tumors,
      suggesting that 5'-CpG island methylation of the FHIT gene is involved in tumor
      development. The authors investigated the status of the 5'-CpG island methylation
      of the FHIT gene and protein expression in a series of 40 cervical carcinomas and
      10 normal cervical epithelial samples, and correlated the data with
      clinicopathological findings. Methylation-specific PCR was applied to detect the
      incidence of the 5'-CpG island methylation, and immunohistochemistry was used for
      FHIT protein staining. 5'-CpG island methylation of the FHIT gene was detected in
      40% (16/40) of the cervical cancer samples and in none of normal cervical
      epithelial specimens. Furthermore, the 5'-CpG island methylation was positively
      associated with clinical stage (p=.002). All the normal cervical epithelial
      samples (10/10) and 90% (36/40) of the cervical carcinomas were positive when the
      unmethylated primer pair was applied. Of the 16 cervical carcinomas with 5'-CpG
      island methylation of the FHIT gene by PCR, 15 showed reduced FHIT protein
      expression. This study suggests that 5'-CpG island methylation plays an important
      role in inactivation of the FHIT gene in cervical cancer.

PMID- 14660281
TI  - Angioganglioglioma: a transitional form between angioglioma and gangioglioma?
AB  - The authors describe for the first time an unusual cerebral tumor with unique
      clinical history, composed of 3 components: pilocytic astrocytoma, vascular
      proliferations similar to those described as arteriovanous malformations, and a
      neoplastic ganglion component. These three components were intimately entangled
      and created the tumor mass. Thus the authors propose the term angioganglioglioma
      for this entity. The relation to the historically defined anglioglioma and tumors
      related to ganglioglioma and dysembryoplastic neuroepithelial tumor is discussed.
      The authors believe that this lesion, in regard to the clinical presentation
      (long course of the disease, clinical symptoms), is closely associated with
      ganglioglioma and, with other morphological features, also to angioglioma.
      Further, it may constitute a new distinct clinicopathological entity with
      neoplastic and hamartomatous features.

PMID- 14660282
TI  - Primitive round cell liposarcoma of the omentum: diagnostic value of
      ultrastructural study.
AB  - A 25-year-old woman presented with abdominal distension first observed 1 month
      earlier. She had a rapidly growing omental tumor that was eventually diagnosed as
      round cell liposarcoma by ultrastructural examination. This case illustrates the
      importance of ultrastructural study and the limitations of immunohistochemistry
      in the diagnosis of such tumors, particularly when they grow in unusual
      locations.

PMID- 14660283
TI  - Pulmonary granulomatous vasculitis induced by insoluble particulates: a case
      report.
AB  - The authors report a case of a 39-year-old woman who sustained an injury to her
      left knee requiring arthroscopic surgical medial menisectomy and ganglionic block
      for reflex sympathetic dystrophy syndrome. Approximately 1 year after injury, the
      patient presented with an elevated white blood cell count and fever and was
      diagnosed to have a psoas muscle abscess, which was treated with antibiotics. She
      was also taking 4 different oral medications that contained microcrystalline
      cellulose as a filter. Approximately 1 month after being diagnosed with the psoas
      muscle abscess, the patient developed shortness of breath, marked weakness,
      diaphoresis, and intermittent emesis. She became hypotensive and tachyneic and
      expired. Postmortem examination showed granulomatous vasculitis with extensive
      occlusions of pulmonary arteries by birefringent crystalline material identified
      to be cellulose histochemically and by analytical electron microscopy evaluation.
      This case report describes the ultrastructural and chemical features of various
      medicinal tablet fillers and compares them to pure samples. This report also
      demonstrates the usefulness of analytical electron microscopy in accurately
      identifying birefringent material in lung tissue.

PMID- 14660284
TI  - Juvenile granulosa cell tumor of the testis: a case presenting as a small round
      cell tumor of childhood.
AB  - We describe the case of a testicular juvenile granulosa cell tumor (JGCT) in a 4
      year-old boy. The highly undifferentiated appearance and robust mitotic activity
      of the neoplasm led to an initial impression of an aggressive, small round cell
      tumor of childhood. Immunocytochemical and ultrastructural studies excluded the
      usual members of that group, and led to the correct diagnosis. To our knowledge,
      this is the oldest reported patient to present with this tumor in the testis, and
      the first with clinical evidence of hormonal activity. The benign behavior of
      testicular JGCT mandates that it be distinguished from other, much more
      aggressive, neoplasms which it may resemble.

PMID- 14660285
TI  - Case for the panel of ultrastructural pathology.

PMID- 14660288
TI  - Reversal of fluoxetine-induced sexual dysfunction by switching to escitalopram.
AB  - Sexual dysfunction is a common complaint among patients taking selective
      serotonin reuptake-inhibiting (SSRI) antidepressants. Many options in managing
      this side effect have been described but none clearly is a first choice among
      clinicians. This paper describes the first published case of a patient having
      successful reversal of SSRI-induced sexual dysfunction by switching from an SSRI
      to escitalopram, the newest antidepressant and SSRI approved for use in the
      United States. Clinical implication is discussed.

PMID- 14660289
TI  - Frequency of marital intercourse among patients with psychiatric and
      psychosomatic disorders in Japan.
AB  - This study investigated the frequency of marital intercourse in 951 patients with
      psychiatric and psychosomatic disorders and compared it to that in a normative
      sample. Only fourteen percent of the patient group had sexual intercourse more
      than once per week; thirty-nine percent were sexually inactive. The groups of
      patients with eating disorders, mood disorders, or any mental or behavioral
      disorders complicated by organic diseases such as cancer, ischemic heart disease,
      and other physical disorders had fewer mean coital frequencies than the controls,
      whereas the coital frequency of patients with anxiety disorders, somatoform
      disorders, sleep disorders, or psychosomatic disorders did not differ
      significantly from that of controls.

PMID- 14660290
TI  - Birth order in transgendered males from Polynesia: a quantitative study of Samoan
      fa'afafine.
AB  - In previous research, a late birth order has been shown to be a characteristic of
      Western homosexual transsexual men. To date, however, it is not clear if a late
      birth order is specific to Western transsexuals or may be a characteristic of non
      Western transgendered males as well. We quantified birth order in a sample of 13
      transgendered males known as fa'afafine from Samoa. On average, the fa'afafine
      were late born, both with regard to number of older brothers and number of older
      sisters, although the effect appeared to be somewhat stronger with regard to
      number of older brothers. We consider possible interpretations of the late birth
      order effect, along with recommendations for further research to identify common
      mechanisms that might underlie transgenderism across different cultural groups.

PMID- 14660292
TI  - The association between religiosity, sexual fantasy, participation in sexual
      acts, sexual enjoyment, exposure, and reaction to sexual materials among black
      South Africans.
AB  - This study investigated the association of religiosity with sexual fantasies,
      participation, enjoyment, exposure, and reaction to sexual materials of 1,292
      first-year university students. Participants who scored higher on the religiosity
      scale were more likely to report fantasies about heterosexual intercourse but
      less likely to have participated in heterosexual intercourse and less likely to
      report enjoyment of heterosexual or lesbian sexual intercourse or oral sex.
      Participants who were more religious were less likely to have been exposed to
      almost all types of sexual material and were more likely to disapprove of almost
      all types of sexual material.

PMID- 14660291
TI  - Validation of the profile of female sexual function (PFSF) in surgically and
      naturally menopausal women.
AB  - The Profile of Female Sexual Function (PFSF) is a patient-based instrument for
      the measuring of loss of sexual function in menopausal women with low libido
      (hypoactive female sexual desire disorder). The instrument, which contains 37
      items in seven domains (sexual desire, arousal, orgasm, sexual pleasure, sexual
      concerns, sexual responsiveness, and sexual self-image) and a single-item measure
      of overall satisfaction with sexuality, has been extensively developed and
      initially validated in over 500 oophorectomized women with low libido in North
      America, Europe, and Australia. Initial validation results showed the PFSF is
      capable of discriminating these patients from age-matched controls and produced
      consistent responses and sensitivity across geographies. The objective of this
      nonrandomized, parallel-group study was to examine the psychometric properties of
      the final PFSF in an independent group of surgically menopausal women with low
      libido and to extend validation to naturally menopausal women with low libido.
      Participants from 16 study centers in North America included surgically (n = 59)
      and naturally (n = 88) menopausal women with low libido and their age-matched
      control subjects, both premenopausal (n = 57) and naturally menopausal (n = 47),
      who reported no problems with libido. Subjects completed the PFSF at baseline and
      again 4 weeks later. Adjusted mean scores for each of the seven domains were
      statistically significantly lower (P < 0.0001) in surgically menopausal women
      with low libido compared with age-matched control women, and in naturally
      menopausal women with low libido compared with naturally menopausal control
      women, demonstrating excellent discriminant validity. Test-retest reliability
      ranged from 0.57 to 0.91 for the seven domain scores, whereas internal
      consistency reliability ranged from 0.74 to 0.95. Results of this research
      support the conclusion that the PFSF is a valid and reliable instrument for
      measurement of loss of sexual function in both naturally and surgically
      menopausal women with low libido.

PMID- 14660293
TI  - Vaginal laser Doppler flowmetry pre- and posthysterectomy.
AB  - The objective of this study was to demonstrate the applicability of laser doppler
      flowmetry to pre- and posthysterectomy vaginal blood flow assessment. We used
      laser Doppler flowmetry to measure pre-and postoperational vaginal blood flow in
      8 premenopausal women undergoing benign hysterectomies; we also measured serum
      E2, FSH, FT and administered a brief sexual function questionnaire. We analyzed
      data using two tailed t-test for paired samples. We found no significant
      differences at the P <.05 level of significance for vaginal blood flow.
      Accompanying values of estradiol, FSH, and free testosterone remained unchanged
      as well. A brief sexual function assessment revealed improvement or stability of
      libido, arousal, orgasm, and partner relatedness. Laser doppler flowmetry is an
      objective, reproducible measure of vaginal blood flow and may be used to
      investigate posthysterectomy sexual function.

PMID- 14660297
TI  - A simple, semi-prescriptive self-assessment model for TQM.
AB  - This article presents a simple, semi-prescriptive self-assessment model for use
      in industry as part of a continuous improvement program such as Total Quality
      Management (TQM). The process by which the model was constructed started with a
      review of the available literature in order to research TQM success factors.
      Next, postal surveys were conducted by sending questionnaires to the winning
      organisations of the Baldrige and European Quality Awards and to a preselected
      group of enterprising UK organisations. From the analysis of this data, the self
      assessment model was constructed to help organisations in their quest for
      excellence. This work confirmed the findings from the literature, that there are
      key factors that contribute to the successful implementation of TQM and these
      have different levels of importance. These key factors, in order of importance,
      are: effective leadership, the impact of other quality-related programs,
      measurement systems, organisational culture, education and training, the use of
      teams, efficient communications, active empowerment of the workforce, and a
      systems infrastructure to support the business and customer-focused processes.
      This analysis, in turn, enabled the design of a self-assessment model that can be
      applied within any business setting. Further work should include the testing and
      review of this model to ascertain its suitability and effectiveness within
      industry today.

PMID- 14660298
TI  - Good clinical laboratory practice (GCLP): the need for a hybrid of good
      laboratory practice and good clinical practice guidelines/standards for medical
      testing laboratories conducting clinical trials in developing countries.
AB  - There has been a significant increase in the number of clinical drug trials
      (particularly phase III) being conducted in developing countries for infectious
      diseases such as HIV, malaria, and tuberculosis. Laboratory results provided by
      medical testing laboratories in the region are critical to ensuring the safety of
      patients and the generation of good quality data. A number of well accepted Good
      Clinical Practice (GCP) and Good Laboratory Practice (GLP) guidelines govern the
      conduct of clinical trials internationally. Good Clinical Practice guidelines
      remain too vague with respect to sample analysis to ensure practical
      implementation in these laboratories. In their strictest sense, Good Laboratory
      Practice guidelines refer to the analysis of samples from non-clinical studies. A
      specific set of minimum standards or requirements for practical implementation of
      clinical trial requirements in medical testing laboratories in the developing
      world is urgently required.

PMID- 14660299
TI  - LIMS user acceptance testing.
AB  - Laboratory Information Management Systems (LIMS) play a key role in the
      pharmaceutical industry. Thorough and accurate validation of such systems is
      critical and is a regulatory requirement. LIMS user acceptance testing is one
      aspect of this testing and enables the user to make a decision to accept or
      reject implementation of the system. This paper discusses key elements in
      facilitating the development and execution of a LIMS User Acceptance Test Plan
      (UATP).

PMID- 14660300
TI  - A single institutional experience: is epoetin alpha effective in anemic children
      with cancer?
AB  - The authors aimed to investigate the efficacy of epoetin-alpha on hemoglobin
      levels and red cell transfusion requirement in children with both hematologic
      malignancy (HM, n = 27) and solid tumors (ST, n = 14). Epoetin-alpha was given
      (150 U/kg or 250 U/kg, thrice weekly) for 12 weeks. Epoetin alpha significantly
      increased the hemoglobin levels at the 2nd and 3rd months of therapy (p <.05). At
      the 3rd month, the patients required less red cell transfusion. At the dose of
      150 U/kg, only three patients with HM, but none of the ST patients, required red
      cell. However, none required red cell transfusion after 2nd month on epoetin
      alpha 250 U/kg. Epoetin-alpha administration increases hemoglobin levels and
      decreases red cell transfusion requirement in children with malignancy.

PMID- 14660301
TI  - Growing Teratoma syndrome treated by interferon alpha-2beta: case report and
      literature review.
AB  - A 14-year old girl was diagnosed as suffering from an immature teratoma. As
      removal of the teratoma was technically unfeasible, the patient was started on
      interferon alpha2beta, 3 MU/day, 5 days per week. On this therapy, the growth of
      the teratoma was stopped and the patient has been well for the past 50 months.
      She continues to be treated with interferon alpha2beta, with almost no side
      effects and no restrictions of her everyday activities, with a good quality of
      life. She is able to attend school regularly, travels abroad frequently, and
      participates fully in everyday activities normal for her age and social
      conditions. Her Karnofsky performance status is 100. This case demonstrates the
      efficacy of interferon alpha2beta therapy in certain instances of growing
      teratoma syndrome, even when the tumorous mass is initially quite large.

PMID- 14660302
TI  - Medulloblastoma in children 0-3 years old: forty years' experience in slovenia.
AB  - Twenty-one children 0-3 years with MB were admitted 1960-1996, of 14 before
      treated 1984, 3 had no treatment, 5 had postoperative RT, one had radioactive
      gold IT. Seven treated 1986-1996 had preradiation Cht, 5 with HDCy. Of the 14
      treated before 1984, 12 died within 1 year, one after 42 years in hypopharynx
      cancer, one is alive, of normal height and working. Of the 7 treated 1986-1996, 3
      with disseminated disease died. Four are longtime survivors, 2 treated with
      reduced doses of RT of normal development. Preradiation Cht with HDCy and reduced
      doses of RT seems to be a reasonable approach.

PMID- 14660303
TI  - Cutaneous angiosarcoma in a patient with xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a DNA repair defect syndrome associated with an
      increased risk to developing skin neoplasms on sun-exposed cutaneous surfaces.
      This report describes the case of a 15-year-old boy with XP who developed
      cutaneous angiosarcoma. The patient was cured with surgery alone, despite
      incomplete resection, and he is alive without evidence of disease 40 months after
      diagnosis. It is the fourth reported case--and the third in pediatric age--of the
      association of XP with this soft part sarcoma.

PMID- 14660304
TI  - Infectious toxicity of dexamethasone during all remission-induction chemotherapy:
      report of two cases and literature review.
AB  - Traditionally, children with acute lymphoblastic leukemia receive prednisone, as
      part of multiagent remission-induction chemotherapy. Recently, many cooperative
      groups use dexamethasone instead of prednisone during induction. We describe the
      infectious toxicities experienced by the first two patients in our institution
      treated with dexamethasone (10 mg/m(2)/day for 4 weeks with gradual tapering)
      during induction according to the dexamethasone arm of BFM 2000 and review the
      relevant literature that suggests an increased risk of infectious complications
      with dexamethasone. Only a prospective two-arm ALL dexamethasone study at two
      dose levels (6 and 10 mg/m(2)/day) will clarify if indeed the higher dose of
      dexamethasone during induction is more effective and without unacceptable
      toxicity.

PMID- 14660305
TI  - Delay in diagnosis of children with cancer: a retrospective study of 315
      children.
AB  - To determine the demographic and systemic parameters in children with solid
      malignancies and to ascertain which of them affected the delay in diagnosis, a
      retrospective study was performed on 315 children diagnosed with a solid tumor at
      our hospital, including epidemiological, social, and medical issues concerning
      the family, the child, the medical system, and the tumor. Lag time, defined as
      the interval between onset of symptoms and final diagnosis, including parent
      delay and physician delay, was estimated for each child. Mean lag time: 15.75
      weeks (w), median: 7 w, range: 0-208 w. Lowest mean values appeared in kidney
      tumors, highest in epithelial, brain and soft tissue sarcomas. Mean parent delay:
      4.42 w, median: 1 w, range: 0-130 w. Mean physician delay: 11.17 w, median: 4 w,
      range: 0-206 w. Among the demographic and personal parameters, the best
      predictors for diagnosis delay were age of child and father's ethnic origin.
      Several factors influenced diagnosis delay of childhood solid tumors. Recognizing
      these factors could minimize the delay, thereby improving the child's chances of
      survival.

PMID- 14660306
TI  - Testicular germ cell tumors in childhood: treatment results of 52 patients.
AB  - We analysed the treatment results of 52 children with testicular germ cell
      tumors. Histopathological diagnoses were endodermal sinus tumor (63.4%),
      embryonal carcinoma (28.8%), teratocarcinoma (5.7%), and mixed tumors (2.1%).
      Radical inguinal orchiectomy was performed in 42 patients and retroperitoneal
      lymph node dissection in 10 (3/10 positive). Overall survival rates were: whole
      group: 71.2%; stage I: 89.7%; II: 68.5%; III: 31.2%; IV: 30% (p =.001). Five-year
      overall survival rates were 85.8% and 100% for stage I patients who received
      chemotherapy or not (p =.27); BEP regimen: 85.7%; classical VAC: 67.9%;
      vinblastine + bleomycin: 63.6%. Chemotherapy is not required in stage I. BEP
      regimen is effective in testicular germ cell tumors.

PMID- 14660307
TI  - Methylation status of the retinoblastoma gene (RB1) in osteosarcoma: no evidence
      for hypermethylation.
AB  - Alterations of the retinoblastoma (RB1) tumor suppressor gene are not only
      associated with retinoblastoma but also with several other malignancies including
      osteosarcoma. Besides direct sequence alterations, hypermethylation of a CpG
      island in the promoter region can cause inactivation of the RB1 gene as it has
      been shown in retinoblastomas. We examined the methylation status of the RB1 gene
      in 25 osteosarcoma specimens by using the methylation-sensitive restriction
      enzymes SacII and SmaI. The restriction fragments were hybridized with clone
      p123, which is a 1.8-kb genomic subclone that spans the RB1 CpG island including
      the promoter region and exon 1. Whereas we reconfirmed hypermethylation of the
      RB1 gene in a sporadic retinoblastoma, no hypermethylation could be detected in
      the 25 osteosarcoma specimens, suggesting that hypermethylation of the RB1
      promoter is not of major importance during osteosarcoma genesis.

PMID- 14660308
TI  - Care of a child dying of cancer: the role of the palliative care team in
      pediatric oncology.
AB  - The last period of life of a child suffering from cancer is of crucial importance
      not only for the child himself but for his parents and relatives as well. The way
      the child dies will remain in the memory of his parents for ever. Multiple
      problems in management of dying child may arise during this last phase. Timely
      and sensitive discussion of such aspects of management as implementation of Do
      Not Resuscitate order, possible provision of fluids and parenteral nutrition,
      initiation of palliative sedation and management of depression is necessary and
      may help parents to better cope with this tragic situation. Palliative care team
      consisting of medical and psychosocial staff plays vital role conveying
      comprehensive and timely management of all these problems and providing all
      necessary assistance for parents and other involved during ones' last weeks,
      days, and hours of child's life. The palliative care team cannot avert
      approaching death but it is responsible for making it as peaceful and as free of
      suffering as possible. This is achieved by vigorous control of all physical
      symptoms in the dying child and by paying close attention to all existential,
      emotional, and social demands of both the child and his relatives.

PMID- 14660309
TI  - Hemostatic side effects of high-dose methotrexate in childhood acute
      lymphoblastic leukemia.
AB  - The purpose of this study is to investigate the hemostatic side effects of HDMTX.
      Between 2001 and 2002, 20 children with acute lymphoblastic leukemia at the Dr.
      Sami Ulus Children's Hospital, Department of Pediatric Hematology and Oncology,
      treated according to the St. Jude ALL XIII protocol were eligible to this study.
      Methotrexate at a dose of 2 g/m(2) was infused over 24 hours. Coagulation
      screening studies included prothrombin time (PT), APTT, fibrinogen, fibrin
      degradation product (D-Dimer), factor II, factor V, factor VII, factor VIII,
      factor IX, factor X, PC, PS, AT-III determinations before HDMTX therapy (PreT), 1
      day after (PostT(1D)), and 1 week after (PostT(1W)) the end of the HDMTX
      infusion. We found that PT and APTT were prolonged, PC, PS, and AT-III levels
      were decreased with a slight increase in D-Dimer 1 day after the administration
      of HDMTX and all of them returned to the normal levels by 7 days. In addition we
      found that FVII, FIX, FX were significantly decreased 1 day after therapy and
      normalised by 7 days.

PMID- 14660310
TI  - Presacral medulloepithelioma--de novo or teratomatous?

PMID- 14660311
TI  - Midazolam compared with ketamine for invasive procedures.
AB  - The combination of ketamine and topical placebo cream was compared with the
      combination of midazolam and topical lidocaine-prilocaine cream (EMLA) in 13
      children with leukaemia undergoing bone marrow punctures. This double-blind,
      randomized, crossover study showed that the children prefer midazolam and EMLA as
      sedation for invasive procedures and that some parents and the nursing staff have
      doubts because of the anxiety during the procedure and the physical restraint
      that often is necessary during midazolam and EMLA. Both methods cause several,
      more or less unpleasant, side effects.

PMID- 14660313
TI  - Making sense of nurses' role in the prevention of suicide in schizophrenia.

PMID- 14660314
TI  - Parenting and childhood behavior problems: mothers' and fathers' voices.
AB  - Through thematic analysis of interviews, we explored parents' perceptions of
      their child's behaviors and their own parenting. A purposive sample of four
      mothers and four fathers who reported behavior problems for their 7(1/2) year-old
      child was selected from a larger study. Parents appraised their child positively
      despite episodic behavior problems, and described parenting in the context of
      financial difficulties, marital conflict, chronic illness, lack of support for
      parenting, and abuse in the parent's family of origin. Data suggest a need for
      timely mental health services to assist parents with managing their child's
      behaviors within the context of the family's situation.

PMID- 14660315
TI  - It's all sacred: African American women's perspectives on spirituality.
AB  - In this study, we examined the meaning and function of spirituality for a group
      of African American women. Participants had been recruited for a focus group
      study exploring the significance of mother-daughter-sister relationships to the
      well being and health behavior choices of women. Women developed individually
      defined concepts of spirituality by combining Judeo-Christian traditions and
      African cosmology. Spirituality was a cornerstone of many participants' daily
      lives. It influenced women's decision-making and behavior across many realms. For
      example, many women came to the conclusion that domestic violence was not part of
      God's plan for their lives. Spiritual-based strategies may provide a rich
      foundation for innovative and efficacious health promotion interventions
      targeting African American women. Clinicians can assist in the co-creation of
      sacred spaces where women can connect with themselves and each other.

PMID- 14660316
TI  - The Centre for Psychiatric Nursing Research and Practice: an innovative approach
      to enhancing clinical nursing research in the psychiatric/mental health field.
AB  - The available nursing literature suggests that nurses engaged in clinical
      practice hold a somewhat ambivalent attitude towards nursing research. On the one
      hand, its value is acknowledged, but on the other, its relevance to clinical
      practice is questioned. This situation poses a significant barrier to the
      involvement of clinicians in research and the utilisation of findings in
      practice. This paper describes the implementation of a model to facilitate the
      development of a systematic research approach at the Centre for Psychiatric
      Nursing Research and Practice in Victoria, Australia. The development of strong
      relationships between the Centre and the clinical field was considered crucial in
      determining the success of this initiative. The introduction of a number of
      programs to foster the conduct and utilisation of clinical research are
      described, including: The Nursing Clinical Development Unit Program, the Clinical
      Research Fellowship Program, clinical research projects, the Collaborative
      Psychiatric Nursing Conference and strategies to encourage the dissemination of
      research information. In combination, these initiatives are expected to
      contribute to a systematic approach to engendering a research culture within
      psychiatric nursing in Victoria, Australia.

PMID- 14660317
TI  - The lived experiences of alcohol addiction: men of alcoholics anonymous.
AB  - Alcohol addiction is one of the most prevalent and debilitating psychiatric
      disorders among the general population. Yet, little has been published on what it
      is like for men to actually experience this disorder. The purpose of this study
      was to identify commonalities in the experience of alcohol addiction among seven
      male members of Alcoholics Anonymous. Using a phenomenological approach, the
      participants completed an audio taped, unstructured, nondirective interview in
      which they were asked to describe their experience of alcohol addiction. The
      interviews were then transcribed and read by a phenomenological research team.
      Four themes were discovered: Emotions, Control, Awareness of Others, and The
      Turning Point, as well as a temporal ground. The authors conclude that mental
      health professionals should encourage alcohol addicted persons to talk about
      their experiences and to help them identify feelings and develop new coping
      skills.

PMID- 14660318
TI  - Child psychiatric hospitalization: the last resort.
AB  - The purpose of this study was to describe how parents manage the experience of
      hospitalizing their school-aged child in a psychiatric unit. Grounded theory
      methodology was used. Thirty-eight parents participated. Data were collected by
      interviews. Analysis was done using the constant comparative method. The basic
      social problem identified was the escalating behavior of the child. The child's
      behavior included self-injurious behavior or violence toward others. The core
      concept was "hospitalization, the last resort." Parents' management of the
      experience varied based on many factors including whether this was the child's
      first psychiatric hospitalization, the distance from the hospital to their home,
      their trust of staff members, sources of support, and their definition of the
      situation.

PMID- 14660319
TI  - The contribution of religious and existential well-being to depression among
      African American heterosexuals with HIV infection.
AB  - The AIDS crisis has challenged black churches to examine how to provide spiritual
      support to individuals who are living with HIV. The dilemmas facing some black
      churches have been specifically related to providing support without embracing
      homosexuality. The doctrine guiding some black churches has caused psychological
      discomfort for both homosexual and heterosexual HIV infected individuals because
      of the stigma associated with HIV. Previous research showed that heterosexuals
      reported more distress than homosexuals. The purpose of this study was to examine
      a subset of African Americans (n = 49) who were heterosexual. Data were drawn
      from a larger data set (N = 117) collected in California. All participants were
      HIV seropositive or had AIDS. A questionnaire examining existential and religious
      well-being, demographic variables, and depression was administered. Religious
      well-being and existential well-being together explained 32% of the variance in
      depression. Implications for mental health nurses are discussed.

PMID- 14660321
TI  - Internet medicine and the evolving legal status of the physician-patient
      relationship.

PMID- 14660322
TI  - The government's increasing use of the False Claims Act against the health care
      industry.

PMID- 14660323
TI  - 2003 LeTourneau Award. Freedom from pain. Establishing a constitutional right to
      pain relief.

PMID- 14660324
TI  - 2003 Schwartz Award. Pitfalls of peer review. The limited protections of state
      and federal peer review law for physicians.

PMID- 14660328
TI  - Poetry and surgery.

PMID- 14660325
TI  - Mandatory provision of foreign language interpreters in health care services.

PMID- 14660329
TI  - Early American medicine.

PMID- 14660330
TI  - Changes in physical capacity among middle-aged municipal employees over 16 years.
AB  - The purpose of the present study was to identify changes in different components
      of physical capacity among middle-aged women and men employed in the municipal
      branch for 16 years. The data were obtained by laboratory measurements and postal
      questionnaires. The study group consisted of 45 middle-aged subjects, who were on
      average 51.5 years old at the beginning of the follow-up in 1981 and 67.3 years
      in 1997. During the 16-year follow-up period, the average physical capacity of
      these workers decreased by approximately 20%. The study showed that the greatest
      changes occurred in isometric trunk muscle strength and in the flexibility of the
      spine, whereas smaller changes were noted in anthropometrics. The decrease of
      physical capacity was greater among men (range 11.6% to 33.7%) than among women
      (range 3.3% to 26.7%), although women had more individual variations. On average,
      people without disease or who were physically active displayed better physical
      capacity than people with disease or who were physically passive.

PMID- 14660331
TI  - Aging and probabilistic learning in single- and multiple-cue tasks.
AB  - The objective of the study was to examine some of the conditions under which
      elderly people are able to learn probabilistic inverse relationships and when
      this type of learning is no longer possible. Two kind of tasks were used: (a) two
      single-cue learning tasks with either direct or inverse relationships (the Single
      Cue Probability Learning paradigm), and (b) three two-cue learning tasks, one
      with two direct relationships, one with a combination of direct and inverse
      relationships, and one with two inverse relationships (the Multiple-Cue
      Probability Learning paradigm). Four groups of participants were included in the
      study: young adults (18- to 25-year-olds), adults (40- to 50-year-olds), elderly
      people (65- to 74-year-olds), and very elderly people (75- to 90-year-olds). It
      was shown that (a) older adults are able to reject the direct relationship
      "default" hypothesis and select the inverse relationship hypothesis when outcome
      feedback contradicting the default hypothesis is given, and provided that the
      learning setting be a very simple one, involving only one cue; (b) some older
      adults are able to select the inverse relationship hypothesis provided that the
      learning setting be a simple one,involving only two inverse relationship cues;
      and (c) very few older adults are able to select the inverse relationship
      hypothesis when the learning setting is a complex one, involving two cues with
      both direct and inverse relationships with the criterion. These results led to
      the revision of the "gradual decrease of cognitive flexibility in older adults"
      hypothesis proposed by Chasseigne, Mullet, and Stewart (Acta Psychologicgrave;a,
      103, 229-238, 1997).

PMID- 14660332
TI  - Executive functioning and judgment-of-learning versus feeling-of-knowing in older
      adults.
AB  - Feeling-of-knowing (FOK) accuracy and judgment-of-learning (JOL) accuracy were
      compared on separate, identical, episodic-memory tasks. The results indicated
      that these two measures were not correlated, suggesting that they do not tap the
      same metacognitive ability. We also looked at whether FOK and JOL accuracies were
      related differently to higher order executive functioning. In order to take
      advantage of within-subject variability in cognitive performance, older adults
      were selected as participants. They were administered the standard
      neuropsychological tests used to assess executive functioning. A correlational
      analysis clearly showed that only FOK accuracy was correlated with the executive
      measures, suggesting that executive control is not equally implicated in FOK and
      JOL.

PMID- 14660333
TI  - Judging older targets' discourse: how do age stereotypes influence evaluations?
AB  - Young adults viewed then read either good or poor descriptions of a cartoon under
      the guise that the descriptions were produced by young (aged 21 years), young-old
      (aged 65 years), or old-old persons (aged 81 years). On a rating of quality,
      description type interacted with target age. For young targets, good descriptions
      were judged as good (assimilation to expectation) and poor were rated as very
      poor (a contrast effect). For young-old targets, for whom expectations were lower
      than for young targets but not as low as for old-old targets, good performance
      was perceived as very good and poor performance very poor (contrast effects). For
      old-old targets for whom negative age stereotyping would lead to lowest
      expectations for performance, poor was rated as poor (assimilation to
      expectation) but good performance was rated as very good (a contrast effect).
      Young raters use a shifting standard to judge the performance of older people.

PMID- 14660334
TI  - The time course of metonymic language text processing by older and younger
      adults.
AB  - The influence of aging on the processing of figurative language was investigated
      by utilizing Frisson and Pickering's (Journal of Experimental Psychology:
      Learning, Memory, and Cognition, 25, 1366-1383, 1999) paradigm, monitoring eye
      fixation times to target words in sentences. First fixation times and total
      fixation times were analyzed for familiar and unfamiliar metonymies and literal
      control sentences. Frisson and Pickering found that processing figurative and
      literal expressions yielded similar patterns of eye fixations. In the current
      study, these methods and results were replicated and extended to include older
      adults' processing of metonymies. This investigation replicated their findings
      for young adults and found that older adults produced the same processing
      patterns as the younger adults.

PMID- 14660335
TI  - Aging and directed forgetting: pre-cue encoding and post-cue rehearsal effects.
AB  - The effects of pre-cue encoding and post-cue rehearsal on item-method-directed
      forgetting in young and older adults were examined. In Experiment 1, level-of
      processing manipulations were used to examine pre-cue representations of items in
      directed forgetting. In Experiment 2, pre-cue levels of processing was
      manipulated as well as post-cue rehearsal time. In general, young adults showed
      greater directed forgetting than older adults, and levels of processing did not
      affect directed forgetting. However, increased post-cue rehearsal time eliminated
      directed forgetting. These findings are discussed in terms of constraints that
      influence item-method-directed forgetting. It is suggested that young adults, but
      not older adults, may use compensatory strategies to overcome these constraints.

PMID- 14660336
TI  - Age-related changes in the spontaneous motor rhythms of the senescence
      accelerated mouse (SAMP8).
AB  - The present study examined the effect of age on the spontaneous motor rhythms of
      mice during wheel running. The spontaneous motor tempo (SMT) of wheel running was
      measured for the P8 strain of the senescence-accelerated mouse (SAMP8) by
      recording the sequence of time intervals (measured in milliseconds) for
      successive revolutions ofa run-wheel over the course of 16 days. Analyses of the
      distribution of interrevolution intervals of 2-, 7-, and 12-month-old SAMP8
      revealed an age-related slowing of wheel running and a corresponding increase in
      variability consistent with Weber's law. All three age groups also demonstrated a
      practice effect over the course of testing best described by a power law. These
      findings provide evidence of age-related changes in the spontaneous motor rhythms
      of the SAMP8 that occur as early as 7 months of age. The results are consistent
      with age-related changes in human subjects and suggest that spontaneous wheel
      running behavior in rodents may be a good model for studying SMT.

PMID- 14660337
TI  - Physiological and community responses of established grassland bacterial
      populations to water stress.
AB  - The effects of water stress upon the diversity and culturable activity of
      bacterial communities in the rhizosphere of an established upland grassland soil
      have been investigated. Intact monoliths were subjected to different watering
      regimens over a 2-month period to study community adaptation to moisture
      limitation and subsequent response to stress alleviation following rewetting.
      Genetic diversity was analyzed with 16S-based denaturing gradient gel
      electrophoresis (DGGE) of total soil-extracted DNA (rRNA genes) and RNA (rRNA
      transcripts) in an attempt to discriminate between total and active communities.
      Physiological response was monitored by plate counts, total counts, and BIOLOG
      GN2 substrate utilization analyses. Controlled soil drying decreased the total
      number of CFU on all the media tested and also decreased the substrate
      utilization response. Following rewetting of dried soil, culture-based analyses
      indicated physiological recovery of the microbial population by the end of the
      experiment. In contrast, DGGE analyses of community 16S rRNA genes, rRNA
      transcripts and cultured communities did not reveal any changes relating to the
      moisture regimens, despite the observed physiological effects. We conclude that
      the imposed moisture regimen modulated the physiological status of the bacterial
      community and that bacterial communities in this soil are resistant to water
      stress. Further, we highlight the need for a reexamination of rRNA transcript
      based molecular profiling techniques as a means of describing the active
      component of soil bacterial communities.

PMID- 14660338
TI  - Cloning, expression, and cell surface localization of Paenibacillus sp. strain W
      61 xylanase 5, a multidomain xylanase.
AB  - We have shown that a xylan-degrading bacterium, W-61, excretes multiple
      xylanases, including xylanase 5 with a molecular mass of 140 kDa. Here, we emend
      the previously used classification of the bacterium (i.e., Aeromonas caviae W-61)
      to Paenibacillus sp. strain W-61 on the basis of the nucleotide sequence of the
      16S rRNA gene, and we clone and express the xyn5 gene encoding xylanase 5 (Xyn5)
      in Escherichia coli and study the subcellular localization of Xyn5. xyn5 encodes
      1,326 amino acid residues, including a 27-amino-acid signal sequence. Sequence
      analysis indicated that Xyn5 comprises two family 22 carbohydrate-binding modules
      (CBM), a family 10 catalytic domain of glycosyl hydrolases, a family 9 CBM, a
      domain similar to the lysine-rich region of Clostridium thermocellum SdbA, and
      three S-layer-homologous (SLH) domains. Recombinant Xyn5 bound to a crystalline
      cellulose, Avicel PH-101, while an N-terminal 90-kDa fragment of Xyn5, which
      lacks the C-terminal half of the family 9 CBM, did not bind to Avicel PH-101.
      Xyn5 was cell bound, and the cell-bound protein was digested by exogenous trypsin
      to produce immunoreactive and xylanolytic fragments with molecular masses of 80
      and 60 kDa. Xyn5 was exclusively distributed in the cell envelope fraction
      consisting of a peptidoglycan-containing layer and an associated S layer. Thus,
      Paenibacillus sp. strain W-61 Xyn5 is a cell surface-anchored modular xylanase
      possessing a functional cellulose-binding module and SLH domains. Possible
      cooperative action of multiple xylanases produced by strain W-61 is discussed on
      the basis of the modular structure of Xyn5.

PMID- 14660339
TI  - Improvement of foreign-protein production in Aspergillus niger var. awamori by
      constitutive induction of the unfolded-protein response.
AB  - Unfolded-protein response (UPR) denotes the upregulation of endoplasmic reticulum
      (ER)-resident chaperone and foldase genes and numerous other genes involved in
      secretory functions during the accumulation of unfolded proteins into the ER.
      Overexpression of individual foldases and chaperones has been used in attempts to
      improve protein production in different production systems. We describe here a
      novel strategy to improve foreign-protein production. We show that the
      constitutive induction of the UPR pathway in Aspergillus niger var. awamori can
      be achieved by expressing the activated form of the transcription factor hacA.
      This induction enhances the production of Trametes versicolor laccase by up to
      sevenfold and of bovine preprochymosin by up to 2.8-fold in this biotechnically
      important fungus. The regulatory range of UPR was studied by analyzing the mRNA
      levels of novel A. niger var. awamori genes involved in different secretory
      functions. This revealed both similarities and differences to corresponding
      studies in Saccharomyces cerevisiae.

PMID- 14660340
TI  - Nitrogen control of atrazine utilization in Pseudomonas sp. strain ADP.
AB  - Pseudomonas sp. strain ADP uses the herbicide atrazine as the sole nitrogen
      source. We have devised a simple atrazine degradation assay to determine the
      effect of other nitrogen sources on the atrazine degradation pathway. The
      atrazine degradation rate was greatly decreased in cells grown on nitrogen
      sources that support rapid growth of Pseudomonas sp. strain ADP compared to cells
      cultivated on growth-limiting nitrogen sources. The presence of atrazine in
      addition to the nitrogen sources did not stimulate degradation. High degradation
      rates obtained in the presence of ammonium plus the glutamine synthetase
      inhibitor MSX and also with an Nas(-) mutant derivative grown on nitrate suggest
      that nitrogen regulation operates by sensing intracellular levels of some key
      nitrogen-containing metabolite. Nitrate amendment in soil microcosms resulted in
      decreased atrazine mineralization by the wild-type strain but not by the Nas(-)
      mutant. This suggests that, although nitrogen repression of the atrazine
      catabolic pathway may have a strong impact on atrazine biodegradation in nitrogen
      fertilized soils, the use of selected mutant variants may contribute to
      overcoming this limitation.

PMID- 14660341
TI  - Investigation of protein export in Bifidobacterium breve UCC2003.
AB  - The molecular interactions between the bifidobacterial cell and its natural
      environment, namely, the gastrointestinal tract of its host, are particularly
      important in understanding the presumed positive effects of Bifidobacterium on
      the health status of the host. In this study an export-specific reporter system,
      designed for use in gram-positive organisms and based on the use of the
      staphylococcal nuclease (Nuc) as a reporter, was employed to identify exported
      proteins in Bifidobacterium breve UCC2003. A B. breve genomic library of
      translational fusions to the Nuc-encoding gene devoid of its own export signal
      was established in the shuttle vector pFUN (I. Poquet, S. D. Ehrlich, and A.
      Gruss, J. Bacteriol. 180:1904-1912, 1998) and screened for bifidobacterial export
      signals. Sequence analysis of the fusion proteins obtained that displayed a
      nuclease-producing phenotype in both Lactococcus lactis and B. breve predicted
      the presence of a classical signal peptide and/or single or multiple
      transmembrane domains, thus indicating that some of the export signals in B.
      breve are comparable to those used in L. lactis. Cell fractionation studies,
      zymograms, nuclease assays, and Western blotting were employed to confirm the
      function of the predicted signals and to determine the location and activity of
      the exported fusion proteins in B. breve and/or L. lactis.

PMID- 14660342
TI  - Identification and distribution of insertion sequences of Paracoccus
      solventivorans.
AB  - Three novel insertion sequences (ISs) (ISPso1, ISPso2, and ISPso3) of the soil
      bacterium Paracoccus solventivorans DSM 11592 were identified by transposition
      into entrapment vector pMEC1. ISPso1 (1,400 bp) carries one large open reading
      frame (ORF) encoding a putative basic protein (with a DDE motif conserved among
      transposases [Tnps] of elements belonging to the IS256 family) with the highest
      levels of similarity with the hypothetical Tnps of Rhodospirillum rubrum and
      Sphingopyxis macrogoltabida. ISPso2 (832 bp) appeared to be closely related to
      ISPpa2 of Paracoccus pantotrophus DSM 11072 and IS1248 of Paracoccus
      denitrificans PdX22, both of which belong to the IS427 group (IS5 family). These
      elements contain two overlapping ORFs and a putative frameshift motif (AAAAG)
      responsible for production of a putative transframe Tnp. ISPso3 (1,286 bp)
      contains a single ORF, whose putative product showed homology with Tnps of ISs
      classified as members of a distinct subgroup of the IS5 group of the IS5 family.
      The highest levels of similarity were observed with ISSsp126 of Sphingomonas sp.
      and IS1169 of Bacteroides fragilis. Analysis of the distribution of ISs of P.
      solventivorans revealed that ISPso2-like elements are the most widely spread of
      the elements in nine species of the genus PARACOCCUS: ISPso1 and ISPso3 are
      present in only a few paracoccal strains, which suggests that they were acquired
      by lateral transfer. Phylogenetic analysis of Tnps of the novel ISs and their
      closest relatives showed their evolutionary relationships and possible directions
      of lateral transfer between various bacterial hosts.

PMID- 14660343
TI  - Nitrate/nitrite assimilation system of the marine picoplanktonic cyanobacterium
      Synechococcus sp. strain WH 8103: effect of nitrogen source and availability on
      gene expression.
AB  - The genes encoding the structural components of the nitrate/nitrite assimilation
      system of the oceanic cyanobacterium Synechococcus sp. strain WH 8103 were cloned
      and characterized. The genes encoding nitrate reductase (narB) and nitrite
      reductase (nirA) are clustered on the chromosome but are organized in separate
      transcriptional units. Upstream of narB is a homologue of nrtP that encodes a
      nitrate/nitrite-bispecific permease rather than the components of an ABC-type
      nitrate transporter found in freshwater cyanobacteria. Unusually, neither nirA
      nor ntcA (encoding a positive transcription factor of genes subject to nitrogen
      control) were found to be tightly regulated by ammonium. Furthermore,
      transcription of glnA (encoding glutamine synthetase) is up-regulated in ammonium
      grown cells, highlighting significant differences in nitrogen control in this
      cyanobacterium. Nitrogen depletion led to the transient up-regulation of ntcA,
      nirA, nrtP, narB, and glnA in what appears to be an NtcA-dependent manner. The
      NtcA-like promoters found upstream of nirA, nrtP, and narB all differ in sequence
      from the canonical NtcA promoter established for other cyanobacteria, and in the
      case of nirA, the NtcA-like promoter was functional only in cells deprived of
      combined nitrogen. The ecological implications of these findings are discussed in
      the context of the oligotrophic nature of oceanic surface waters in which
      Synechococcus spp. thrive.

PMID- 14660344
TI  - Carbon source-induced modifications in the mycolic acid content and cell wall
      permeability of Rhodococcus erythropolis E1.
AB  - The influence of the carbon source on cell wall properties was analyzed in an
      efficient alkane-degrading strain of Rhodococcus erythropolis (strain E1), with
      particular focus on the mycolic acid content. A clear correlation was observed
      between the carbon source and the mycolic acid profiles as estimated by high
      performance liquid chromatography and mass spectrometry. Two types of mycolic
      acid patterns were observed after growth either on saturated linear alkanes or on
      short-chain alkanoates. One type of pattern was characterized by the lack of odd
      numbered carbon chains and resulted from growth on linear alkanes with even
      numbers of carbon atoms. The second type of pattern was characterized by mycolic
      acids with both even- and odd-numbered carbon chains and resulted from growth on
      compounds with odd-numbered carbon chains, on branched alkanes, or on mixtures of
      different compounds. Cellular short-chain fatty acids were twice as abundant
      during growth on a branched alkane (pristane) as during growth on acetate, while
      equal amounts of mycolic acids were found under both conditions. More hydrocarbon
      like compounds and less polysaccharide were exposed at the cell wall surface
      during growth on alkanes. Whatever the substrate, the cells had the same affinity
      for aqueous-nonaqueous solvent interfaces. By contrast, bacteria displayed
      completely opposite susceptibilities to hydrophilic and hydrophobic antibiotics
      and were found to be strongly stained by hydrophobic dyes after growth on
      pristane but not after growth on acetate. Taken together, these data show that
      the cell wall composition of R. erythropolis E1 is influenced by the nutritional
      regimen and that the most marked effect is a radical change in cell wall
      permeability.

PMID- 14660345
TI  - Shigella dysenteriae type 1-specific bacteriophage from environmental waters in
      Bangladesh.
AB  - Shigella dysenteriae type 1 is the causative agent of the most severe form of
      bacillary dysentery, which occurs as epidemics in many developing countries. We
      isolated a bacteriophage from surface water samples from Bangladesh that
      specifically lyses strains of S. dysenteriae type 1. This phage, designated SF-9,
      belongs to the Podoviridae family and has a 41-kb double-stranded DNA genome.
      Further screening of water samples for the prevalence of the phage revealed 9 of
      71 (12.6%) water samples which were positive for the phage. These water samples
      were also positive in PCR assays for one or more S. dysenteriae type 1-specific
      genes, including ipaBCD and stx1, and live S. dysenteriae type 1 was isolated
      from three phage-positive samples. The results of this study suggest that phage
      SF-9 may have epidemiological applications in tracing the presence of S.
      dysenteriae type 1 in environmental waters.

PMID- 14660346
TI  - Compatible solutes protect against chaotrope (ethanol)-induced, nonosmotic water
      stress.
AB  - Water stress is one of the major stresses experienced by cellular systems and can
      take a number of distinct forms. In response to turgor-related osmotic stress,
      cells produce compatible solutes that are macromolecule protectants and also
      counteract the outflow of water from stressed cells. In this report we show that
      the germination of conidia of Aspergillus nidulans, a sensitive indicator of
      water stress, in the presence of ethanol is correlated with the intracellular
      concentration of the compatible solutes glycerol and erythritol, which protect
      against both osmotic and nonturgor forms of water stress.

PMID- 14660347
TI  - Role of soil pH in the development of enhanced biodegradation of fenamiphos.
AB  - Repeated treatment with fenamiphos (ethyl 4-methylthio-m-tolyl
      isopropylphosphoramidate) resulted in enhanced biodegradation of this nematicide
      in two United Kingdom soils with a high pH (>/= 7.7). In contrast, degradation of
      fenamiphos was slow in three acidic United Kingdom soils (pH 4.7 to 6.7), and
      repeated treatments did not result in enhanced biodegradation. Rapid degradation
      of fenamiphos was observed in two Australian soils (pH 6.7 to 6.8) in which it
      was no longer biologically active against plant nematodes. Enhanced degrading
      capability was readily transferred from Australian soil to United Kingdom soils,
      but only those with a high pH were able to maintain this capability for extended
      periods of time. This result was confirmed by fingerprinting bacterial
      communities by 16S rRNA gene profiling of extracted DNA. Only United Kingdom
      soils with a high pH retained bacterial DNA bands originating from the fenamiphos
      degrading Australian soil. A degrading consortium was enriched from the
      Australian soil that utilized fenamiphos as a sole source of carbon. The 16S rRNA
      banding pattern (determined by denaturing gradient gel electrophoresis) from the
      isolated consortium migrated to the same position as the bands from the
      Australian soil and those from the enhanced United Kingdom soils in which the
      Australian soil had been added. When the bands from the consortium and the soil
      were sequenced and compared they showed between 97 and 100% sequence identity,
      confirming that these groups of bacteria were involved in degrading fenamiphos in
      the soils. The sequences obtained showed similarity to those from the genera
      Pseudomonas, Flavobacterium, and CAULOBACTER: In the Australian soils, two
      different degradative pathways operated simultaneously: fenamiphos was converted
      to fenamiphos sulfoxide (FSO), which was hydrolyzed to the corresponding phenol
      (FSO-OH) or was hydrolyzed directly to fenamiphos phenol. In the United Kingdom
      soils in which enhanced degradation had been induced, fenamiphos was oxidized to
      FSO and then hydrolyzed to FSO-OH, but direct conversion to fenamiphos phenol did
      not occur.

PMID- 14660348
TI  - Molecular characterization of community structures and sulfur metabolism within
      microbial streamers in Japanese hot springs.
AB  - Community structures of submerged microbial slime streamers (SMSS) in sulfide
      containing hot springs at 72 to 80 degrees C at Nakabusa and Yumata, Japan, were
      investigated by molecular analysis based on the 16S rRNA gene. The SMSS were
      classified into two consortia; consortium I occurred at lower levels of sulfide
      in the hot springs (less than 0.1 mM), and consortium II dominated when the
      sulfide levels were higher (more than 0.1 mM). The dominant cell morphotypes in
      consortium I were filamentous and small rod-shaped cells. The filamentous cells
      hybridized with fluorescent oligonucleotide probes for the domain Bacteria, the
      domain Archaea, and the family Aquificaceae: Our analysis of the denaturing
      gradient gel electrophoresis (DGGE) bands by using reverse transcription (RT)-PCR
      amplification with two primer sets (Eub341-F with the GC clamp and Univ907R for
      the Bacteria and Eub341-F with the GC clamp and Arch915R) indicated that dominant
      bands were phylogenetically related to microbes in the genus Aquifex: On the
      other hand, consortium II was dominated by long, small, rod-shaped cells, which
      hybridized with the oligonucleotide probe S-*-Tdes-0830-a-A-20 developed in this
      study for the majority of as-yet-uncultivated microbes in the class
      Thermodesulfobacteria: The dominant DGGE band obtained by PCR and RT-PCR was
      affiliated with the genus Sulfurihydrogenibium: Moreover, our analysis of
      dissimilatory sulfite reductase (DSR) gene sequences retrieved from both
      consortia revealed a high frequency of DSR genes corresponding to the DSR of
      Thermodesulfobacteria-like microorganisms. Using both sulfide monitoring and
      (35)SO(4)(2-) tracer experiments, we observed microbial sulfide production and
      consumption by SMSS, suggesting that there is in situ sulfide production by as
      yet-uncultivated Thermodesulfobacteria-like microbes and there is in situ sulfide
      consumption by Sulfurihydrogenibium-like microbes within the SMSS in the Nakabusa
      and Yumata hot springs.

PMID- 14660349
TI  - Use of borate to control the 5'-position-selective microbial glucosylation of
      pyridoxine.
AB  - Nearly 100% 5'-position selectivity of transglucosylation from maltodextrin to
      pyridoxine (PN) by cells of Verticillium dahliae TPU 4900 was observed when the
      reaction was carried out with borate. The same effect of borate was observed not
      only during synthesis of pyridoxine 5'-alpha-D-glucoside by partially purified
      enzyme of this strain but also during synthesis of this compound by other
      microorganisms and with other enzymes (alpha-glucosidase and cyclomaltodextrin
      glucanotransferase). The effect was thought to be caused by the formation of a
      borate complex with 3- and 4'-position hydroxyl groups of PN. A decrease in the
      formation of pyridoxine 5'-alpha-D-glucoside was observed in the reaction with
      borate, but this decrease was overcome by optimizing the pH and increasing the
      amount of cells in the reaction mixture.

PMID- 14660350
TI  - Linked redox precipitation of sulfur and selenium under anaerobic conditions by
      sulfate-reducing bacterial biofilms.
AB  - A biofilm-forming strain of sulfate-reducing bacteria (SRB), isolated from a
      naturally occurring mixed biofilm and identified by 16S rDNA analysis as a strain
      of Desulfomicrobium norvegicum, rapidly removed 200 micro M selenite from
      solution during growth on lactate and sulfate. Elemental selenium and elemental
      sulfur were precipitated outside SRB cells. Precipitation occurred by an abiotic
      reaction with bacterially generated sulfide. This appears to be a generalized
      ability among SRB, arising from dissimilatory sulfide biogenesis, and can take
      place under low redox conditions and in the dark. The reaction represents a new
      means for the deposition of elemental sulfur by SRB under such conditions. A
      combination of transmission electron microscopy, environmental scanning electron
      microscopy, and cryostage field emission scanning electron microscopy were used
      to reveal the hydrated nature of SRB biofilms and to investigate the location of
      deposited sulfur-selenium in relation to biofilm elements. When pregrown SRB
      biofilms were exposed to a selenite-containing medium, nanometer-sized selenium
      sulfur granules were precipitated within the biofilm matrix. Selenite was
      therefore shown to pass through the biofilm matrix before reacting with
      bacterially generated sulfide. This constitutes an efficient method for the
      removal of toxic concentrations of selenite from solution. Implications for
      environmental cycling and the fate of sulfur and selenium are discussed, and a
      general model for the potential action of SRB in selenium transformations is
      presented.

PMID- 14660351
TI  - High-yield production of a bacterial xylanase in the filamentous fungus
      Trichoderma reesei requires a carrier polypeptide with an intact domain
      structure.
AB  - A bacterial xylanase gene, Nonomuraea flexuosa xyn11A, was expressed in the
      filamentous fungus Trichoderma reesei from the strong cellobiohydrolase 1
      promoter as fusions to a variety of carrier polypeptides. By using single-copy
      isogenic transformants, it was shown that production of this xylanase was clearly
      increased (up to 820 mg/liter) when it was produced as a fusion protein with a
      carrier polypeptide having an intact domain structure compared to the production
      (150 to 300 mg/liter) of fusions to the signal sequence alone or to carriers
      having incomplete domain structures. The carriers tested were the T. reesei
      mannanase I (Man5A, or MANI) core-hinge and a fragment thereof and the cellulose
      binding domain of T. reesei cellobiohydrolase II (Cel6A, or CBHII) with and
      without the hinge region(s) and a fragment thereof. The flexible hinge region was
      shown to have a positive effect on both the production of Xyn11A and the
      efficiency of cleavage of the fusion polypeptide. The recombinant Xyn11A produced
      had properties similar to those of the native xylanase. It constituted 6 to 10%
      of the total proteins secreted by the transformants. About three times more of
      the Man5A core-hinge carrier polypeptide than of the recombinant Xyn11A was
      observed. Even in the best Xyn11A producers, the levels of the fusion mRNAs were
      only approximately 10% of the level of cel7A (cbh1) mRNA in the untransformed
      host strain.

PMID- 14660352
TI  - Use of multiplex reverse transcription-PCR to study the expression of a laccase
      gene family in a basidiomycetous fungus.
AB  - Laccases produced by white rot fungi are involved in the degradation of lignin
      and a broad diversity of other natural and synthetic molecules, having a great
      potential for biotechnological applications. They are frequently encoded by gene
      families, as in the basidiomycete Trametes sp. strain I-62, from which the lcc1,
      lcc2, and lcc3 laccase genes have been cloned and sequenced. A multiplex reverse
      transcription-PCR method to simultaneously study the expression of these genes
      was developed in this study. The assay proved to be quick, simple, highly
      sensitive, and reproducible and is particularly valuable when numerous samples
      are to be analyzed and/or if the amount of initial mRNA is limited. It was used
      to analyze the effect of 3,4-dimethoxybenzyl alcohol (veratryl alcohol) and two
      of its isomers (2,5-dimethoxybenzyl alcohol and 3,5-dimethoxybenzyl alcohol) on
      differential laccase gene expression in Trametes sp. strain I-62. These aromatic
      compounds produced different induction patterns despite their chemical
      similarity. We found 2,5-dimethoxybenzyl alcohol to be the best inducer of
      laccase activity while also producing the highest increase in gene expression;
      3,5-dimethoxybenzyl alcohol was the next best inducer. Transcript amounts of each
      gene fluctuated dramatically in the presence of these three inducers, while the
      total amounts of laccase mRNAs seemed to be modulated by a coordinated regulation
      of the different genes.

PMID- 14660353
TI  - Nitrification and nitrifying bacteria in the lower Seine River and estuary
      (France).
AB  - The Acheres wastewater treatment plant, located just downstream of Paris,
      discharges its effluents into the lower Seine River. The effluents contain large
      numbers of heterotrophic bacteria, organic matter, and ammonium and are a source
      of nitrifying bacteria. As a result, degradation of organic matter by
      heterotrophic bacteria and subsequent oxygen depletion occur immediately
      downstream of the effluent outlet, whereas nitrifying bacteria apparently need to
      build up a significant biomass before ammonium oxidation significantly depletes
      the oxygen. We quantified the potential total nitrifying activity and the
      potential activities of the ammonia- and nitrite-oxidizing communities along the
      Seine River. In the summer, the maximum nitrifying activity occurs in the upper
      freshwater estuary, approximately 200 km downstream of Acheres. The quantities of
      nitrifying bacteria, based on amoA gene copy numbers, and of Nitrobacter
      organisms, based on 16S rRNA gene copy numbers, were correlated with the
      potential nitrifying activities. The species composition of ammonia-oxidizing
      bacteria was investigated at two sites: the Triel station just downstream from
      Acheres (km 84) and the Seine freshwater estuary at the Duclair station (km 278).
      By means of PCR primers targeting the amoA gene, a gene library was created.
      Phylogenetic analysis revealed that the majority of the analyzed clones at both
      sites were affiliated with the genus NITROSOMONAS: The Nitrosomonas oligotropha-
      and Nitrosomonas urea-related clones represented nearly 81% of the community of
      ammonia-oxidizing bacteria at Triel and 60% at Duclair. Two other ammonia
      oxidizing clusters of the beta subclass of the Proteobacteria, i.e., Nitrosomonas
      europaea- and Nitrosospira-like bacteria, were found in smaller numbers. The
      major change in the ammonia-oxidizing community between the two stations along
      the Seine River-upper estuary continuum was the replacement of the N. oligotropha
      and N. urea-related bacteria by the Nitrosospira-affiliated bacteria. Although
      the diversities of the ammonia oxidizers appear to be similar for the two sites,
      only half of the restriction patterns are common to both sites, which could be
      explained by the differences in ammonium concentrations, which are much lower in
      the upper estuary than in the river at the effluent outlet. These results imply a
      significant immigration and/or selection of the ammonia-oxidizing bacterial
      population along the continuum of the Seine River from Paris to the estuary.

PMID- 14660354
TI  - Controlled modulation of folate polyglutamyl tail length by metabolic engineering
      of Lactococcus lactis.
AB  - The dairy starter bacterium Lactococcus lactis is able to synthesize folate and
      accumulates >90% of the produced folate intracellularly, predominantly in the
      polyglutamyl form. Approximately 10% of the produced folate is released into the
      environment. Overexpression of folC in L. lactis led to an increase in the length
      of the polyglutamyl tail from the predominant 4, 5, and 6 glutamate residues in
      wild-type cells to a maximum of 12 glutamate residues in the folate synthetase
      overproducer and resulted in a complete retention of folate in the cells.
      Overexpression of folKE, encoding the bifunctional protein 2-amino-4-hydroxy-6
      hydroxymethyldihydropteridine pyrophosphokinase and GTP-cyclohydrolase I,
      resulted in reduction of the average polyglutamyl tail length, leading to
      enhanced excretion of folate. By simultaneous overexpression of folKE and folC,
      encoding the enzyme folate synthetase or polyglutamyl folate synthetase, the
      average polyglutamyl tail length was increased, again resulting in normal wild
      type distribution of folate. The production of bioavailable monoglutamyl folate
      and almost complete release of folate from the bacterium was achieved by
      expressing the gene for gamma-glutamyl hydrolase from human or rat origin. These
      engineering studies clearly establish the role of the polyglutamyl tail length in
      intracellular retention of the folate produced. Also, the potential application
      of engineered food microbes producing folates with different tail lengths is
      discussed.

PMID- 14660355
TI  - Efficient degradation of 2,4,6-Trichlorophenol requires a set of catabolic genes
      related to tcp genes from Ralstonia eutropha JMP134(pJP4).
AB  - 2,4,6-Trichlorophenol (2,4,6-TCP) is a hazardous pollutant. Several aerobic
      bacteria are known to degrade this compound. One of these, Ralstonia eutropha
      JMP134(pJP4), a well-known, versatile chloroaromatic compound degrader, is able
      to grow in 2,4,6-TCP by converting it to 2,6-dichlorohydroquinone, 6
      chlorohydroxyquinol, 2-chloromaleylacetate, maleylacetate, and beta-ketoadipate.
      Three enzyme activities encoded by tcp genes, 2,4,6-TCP monooxygenase (tcpA), 6
      chlorohydroxyquinol 1,2-dioxygenase (tcpC), and maleylacetate reductase (tcpD),
      are involved in this catabolic pathway. Here we provide evidence that all these
      tcp genes are clustered in the R. eutropha JMP134(pJP4) chromosome, forming the
      putative catabolic operon tcpRXABCYD. We studied the presence of tcp-like gene
      sequences in several other 2,4,6-TCP-degrading bacterial strains and found two
      types of strains. One type includes strains belonging to the Ralstonia genus and
      possessing a set of tcp-like genes, which efficiently degrade 2,4,6-TCP and
      therefore grow in liquid cultures containing this chlorophenol as a sole carbon
      source. The other type includes strains belonging to the genera Pseudomonas,
      Sphingomonas, or Sphingopixis, which do not have tcp-like gene sequences and
      degrade this pollutant less efficiently and which therefore grow only as small
      colonies on plates with 2,4,6-TCP. Other than strain JMP134, none of the
      bacterial strains whose genomes have been sequenced possesses a full set of tcp
      like gene sequences.

PMID- 14660356
TI  - Purification and characterization of alpha-L-arabinopyranosidase and alpha-L
      arabinofuranosidase from Bifidobacterium breve K-110, a human intestinal
      anaerobic bacterium metabolizing ginsenoside Rb2 and Rc.
AB  - Two arabinosidases, alpha-L-arabinopyranosidase (no EC number) and alpha-L
      arabinofuranosidase (EC 3.2.1.55), were purified from ginsenoside-metabolizing
      Bifidobacterium breve K-110, which was isolated from human intestinal microflora.
      alpha-L-Arabinopyranosidase was purified to apparent homogeneity, using a
      combination of ammonium sulfate fractionation, DEAE-cellulose, butyl Toyopearl,
      hydroxyapatite Ultrogel, QAE-cellulose, and Sephacryl S-300 HR column
      chromatography, with a final specific activity of 8.81 micro mol/min/mg. alpha-L
      Arabinofuranosidase was purified to apparent homogeneity, using a combination of
      ammonium sulfate fractionation, DEAE-cellulose, butyl Toyopearl, hydroxyapatite
      Ultrogel, Q-Sepharose, and Sephacryl S-300 column chromatography, with a final
      specific activity of 6.46 micro mol/min/mg. The molecular mass of alpha-L
      arabinopyranosidase was found to be 310 kDa by gel filtration, consisting of four
      identical subunits (77 kDa each, measured by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis [SDS-PAGE]), and that of alpha-L
      arabinofuranosidase was found to be 60 kDa by gel filtration and SDS-PAGE. alpha
      L-Arabinopyranosidase and alpha-L-arabinofuranosidase showed optimal activity at
      pH 5.5 to 6.0 and 40 degrees C and pH 4.5 and 45 degrees C, respectively. Both
      purified enzymes were potently inhibited by Cu(2+) and p
      chlormercuryphenylsulfonic acid. alpha-L-Arabinopyranosidase acted to the
      greatest extent on p-nitrophenyl-alpha-L-arabinopyranoside, followed by
      ginsenoside Rb2. alpha-L-Arabinofuranosidase acted to the greatest extent on p
      nitrophenyl-alpha-L-arabinofuranoside, followed by ginsenoside Rc. Neither enzyme
      acted on p-nitrophenyl-beta-galactopyranoside or p-nitrophenyl-beta-D
      fucopyranoside. These findings suggest that the biochemical properties and
      substrate specificities of these purified enzymes are different from those of
      previously purified alpha-L-arabinosidases. This is the first reported
      purification of alpha-L-arabinopyranosidase from an anaerobic Bifidobacterium sp.

PMID- 14660357
TI  - Inactivation of Geobacillus stearothermophilus spores by high-pressure carbon
      dioxide treatment.
AB  - High-pressure CO2 treatment has been studied as a promising method for
      inactivating bacterial spores. In the present study, we compared this method with
      other sterilization techniques, including heat and pressure treatment. Spores of
      Bacillus coagulans, Bacillus subtilis, Bacillus cereus, Bacillus licheniformis,
      and Geobacillus stearothermophilus were subjected to CO2 treatment at 30 MPa and
      35 degrees C, to high-hydrostatic-pressure treatment at 200 MPa and 65 degrees C,
      or to heat treatment at 0.1 MPa and 85 degrees C. All of the bacterial spores
      except the G. stearothermophilus spores were easily inactivated by the heat
      treatment. The highly heat- and pressure-resistant spores of G.
      stearothermophilus were not the most resistant to CO2 treatment. We also
      investigated the influence of temperature on CO2 inactivation of G.
      stearothermophilus. Treatment with CO2 and 30 MPa of pressure at 95 degrees C for
      120 min resulted in 5-log-order spore inactivation, whereas heat treatment at 95
      degrees C for 120 min and high-hydrostatic-pressure treatment at 30 MPa and 95
      degrees C for 120 min had little effect. The activation energy required for CO2
      treatment of G. stearothermophilus spores was lower than the activation energy
      for heat or pressure treatment. Although heat was not necessary for
      inactivationby CO2 treatment of G. stearothermophilus spores, CO2 treatment at 95
      degrees C was more effective than treatment at 95 degrees C alone.

PMID- 14660358
TI  - Molecular surveillance of enterovirus and norwalk-like virus in oysters relocated
      to a municipal-sewage-impacted gulf estuary.
AB  - An 18-month survey was conducted to examine the prevalence of enteric viruses and
      their relationship to indicators in environmentally polluted shellfish. Groups of
      oysters, one group per 4 weeks, were relocated to a coastal water area in the
      Gulf of Mexico that is impacted by municipal sewage and were analyzed for
      enteroviruses, Norwalk-like viruses (NLV), and indicator microorganisms (fecal
      coliform, Escherichia coli, and male-specific coliphages). The levels of
      indicator microorganisms were consistent with the expected continuous pollution
      of the area. Fourteen of the 18 oyster samples were found by reverse
      transcription (RT)-PCR to harbor NLV and/or enterovirus sequences. Of the four
      virus-negative oysters, three had exposure to water temperatures of >29 degrees
      C. Concomitant with these findings, two of these four oysters also accumulated
      the lowest levels of coliphages. PCR primers targeting pan-enteroviruses and the
      NLV 95/96-US common subset were utilized; NLV sequences were detected more
      frequently than those of enteroviruses. Within the 12-month sampling period, NLV
      and enterovirus sequences were detected in 58 and 42%, respectively, of the
      oysters (67% of the oysters tested were positive for at least one virus) from a
      prohibited shellfish-growing area approximately 30 m away from a sewage discharge
      site. Eight (4.6%) of the 175 NLV capsid nucleotide sequences were heterogeneous
      among the clones derived from naturally polluted oysters. Overall, enteric viral
      sequences were found in the contaminated oysters throughout all seasons except
      hot summer, with a higher prevalence of NLV than enterovirus. Although a high
      percentage of the oysters harbored enteric viruses, the virus levels were usually
      less than or equal to 2 logs of RT-PCR-detectable units per gram of oyster meat.

PMID- 14660359
TI  - Real-time PCR analysis of Vibrio vulnificus from oysters.
AB  - Vibrio vulnificus is an opportunistic human pathogen commonly found in estuarine
      environments. Infections are associated with raw oyster consumption and can
      produce rapidly fatal septicemia in susceptible individuals. Standard enumeration
      of this organism in shellfish or seawater is laborious and inaccurate; therefore,
      more efficient assays are needed. An oligonucleotide probe derived from the
      cytolysin gene, vvhA, was previously used for colony hybridizations to enumerate
      V. vulnificus. However, this method requires overnight growth, and vibrios may
      lack culturability under certain conditions. In the present study, we targeted
      the same locus for development of a TaqMan real-time PCR assay. Probe specificity
      was confirmed by amplification of 28 V. vulnificus templates and by the lack of a
      PCR product with 22 non-V. vulnificus strains. Detection of V. vulnificus in pure
      cultures was observed over a 6-log-unit linear range of concentration (10(2) to
      10(8) CFU ml(-1)), with a lower limit of 72 fg of genomic DNA micro l of PCR
      mixture(-1) or the equivalent of six cells. Similar sensitivity was observed in
      DNA extracted from mixtures of V. vulnificus and V. parahaemolyticus cells. Real
      time PCR enumeration of artificially inoculated oyster homogenates correlated
      well with colony hybridization counts (r(2) = 0.97). Numbers of indigenous V.
      vulnificus cells in oysters by real-time PCR showed no significant differences
      from numbers from plate counts with probe (t test; P = 0.43). Viable but
      nonculturable cells were also enumerated by real-time PCR and confirmed by the
      BacLight viability assay. These data indicate that real-time PCR can provide
      sensitive species-specific detection and enumeration of V. vulnificus in seafood.

PMID- 14660360
TI  - Identification and characterization of benzimidazole resistance in Monilinia
      fructicola from stone fruit orchards in California.
AB  - Low and high levels of resistance to the benzimidazole fungicides benomyl and
      thiophanate-methyl were observed in field isolates of Monilinia fructicola, which
      is the causative agent of brown rot of stone fruit. Isolates that had low levels
      of resistance (hereafter referred to as LR isolates) and high levels of
      resistance (hereafter referred to as HR isolates) were also cold and heat
      sensitive, respectively. Results from microsatellite DNA fingerprints showed that
      genetic identities among the populations of sensitive (S), LR, and HR isolates
      were very high (>0.96). Analysis of DNA sequences of the beta-tubulin gene showed
      that the LR isolates had a point mutation at codon 6, causing a replacement of
      the amino acid histidine by tyrosine. Codon 198, which encodes a glutamic acid in
      S and LR isolates, was converted to a codon for alanine in HR isolates. Based on
      these point mutations in the beta-tubulin gene, allele-specific PCR assays were
      developed for rapid detection of benzimidazole-resistant isolates of M.
      fructicola from stone fruit.

PMID- 14660361
TI  - Prevalence and antimicrobial resistance of enterococcus species isolated from
      retail meats.
AB  - From March 2001 to June 2002, a total of 981 samples of retail raw meats
      (chicken, turkey, pork, and beef) were randomly obtained from 263 grocery stores
      in Iowa and cultured for the presence of Enterococcus spp. A total of 1,357
      enterococcal isolates were recovered from the samples, with contamination rates
      ranging from 97% of pork samples to 100% of ground beef samples. Enterococcus
      faecium was the predominant species recovered (61%), followed by E. faecalis
      (29%), and E. hirae (5.7%). E. faecium was the predominant species recovered from
      ground turkey (60%), ground beef (65%), and chicken breast (79%), while E.
      faecalis was the predominant species recovered from pork chops (54%). The
      incidence of resistance to many production and therapeutic antimicrobials
      differed among enterococci recovered from retail meat samples. Resistance to
      quinupristin-dalfopristin, a human analogue of the production drug virginiamycin,
      was observed in 54, 27, 9, and 18% of E. faecium isolates from turkey, chicken,
      pork, and beef samples, respectively. No resistance to linezolid or vancomycin
      was observed, but high-level gentamicin resistance was observed in 4% of
      enterococci, the majority of which were recovered from poultry retail meats.
      Results indicate that Enterococcus spp. commonly contaminate retail meats and
      that dissimilarities in antimicrobial resistance patterns among enterococci
      recovered from different meat types may reflect the use of approved antimicrobial
      agents in each food animal production class.

PMID- 14660362
TI  - Biochemical, genetic, and zoosporicidal properties of cyclic lipopeptide
      surfactants produced by Pseudomonas fluorescens.
AB  - Zoospores play an important role in the infection of plant and animal hosts by
      oomycetes and other zoosporic fungi. In this study, six fluorescent Pseudomonas
      isolates with zoosporicidal activities were obtained from the wheat rhizosphere.
      Zoospores of multiple oomycetes, including Pythium species, Albugo candida, and
      Phytophthora infestans, were rendered immotile within 30 s of exposure to cell
      suspensions or cell culture supernatants of the six isolates, and subsequent
      lysis occurred within 60 s. The representative strain SS101, identified as
      Pseudomonas fluorescens biovar II, reduced the surface tension of water from 73
      to 30 mN m-1. The application of cell suspensions of strain SS101 to soil or
      hyacinth bulbs provided significant protection against root rot caused by Pythium
      intermedium. Five Tn5 mutants of strain SS101lacked the abilities to reduce the
      surface tension of water and to cause lysis of zoospores. Genetic
      characterization of two surfactant-deficient mutants showed that the transposons
      had integrated into condensation domains of peptide synthetases. A partially
      purified extract from strain SS101 reduced the surface tension of water to 30 mN
      m-1 and reached the critical micelle concentration at 25 micrograms ml-1. Reverse
      phase high-performance liquid chromatography yielded eight different fractions,
      five of which had surface activity and caused lysis of zoospores. Mass
      spectrometry and nuclear magnetic resonance analyses allowed the identification
      of the main constituent as a cyclic lipopeptide (1,139 Da) containing nine amino
      acids and a 10-carbon hydroxy fatty acid. The other four zoosporicidal fractions
      were closely related to the main constituent, with molecular massesranging from
      1,111 to 1,169 Da.

PMID- 14660363
TI  - Heat shock treatment increases the frequency of loss of an erythromycin
      resistance-encoding transposable element from the chromosome of Lactobacillus
      crispatus CHCC3692.
AB  - A 3,165-bp chromosomally integrated transposon, designatedTn3692, of the gram
      positive strain Lactobacillus crispatus CHCC3692 contains an erm(B) gene
      conferring resistance to erythromycin at concentrations of up to 250
      micrograms/ml. Loss of this resistance can occur spontaneously, but the rate is
      substantially increased by heat shock treatment. Heat shock treatment at 60
      degrees C resulted in an almost 40-fold increase in the frequency of erythromycin
      sensitive cells (erythromycin MIC, 0.047 micrograms/ml). The phenotypic change
      was followed by a dramatic increase in transcription of the transposase gene and
      the concomitant loss of an approximately 2-kb DNA fragment carrying the erm(B)
      gene from the 3,165-bp erm transposon. In cells that were not subjected to heat
      shock, transcription of the transposase gene was not detectable. The upstream
      sequence of the transposase gene did not show any homology to known heat shock
      promoters in the gene data bank. Significant homology (>99%) was observed between
      the erythromycin resistance-encoding gene from L. crispatus CHCC3692 and the
      erm(B) genes from other gram-positive bacteria, such as Streptococcus agalactiae,
      Streptococcus pyogenes, Enterococcus faecium, and Lactobacillus reuteri, which
      strongly indicates a common origin of the erm(B) gene for these species. The
      transposed DNA element was not translocated to other parts of the genome of
      CHCC3692, as determining by Southern blotting, PCR analysis, and DNA sequencing.
      No other major aberrations were observed, as judged by colony morphology, growth
      performance of the strain, and pulsed-field gel electrophoresis. These
      observations suggest that heat shock treatment could be used as a tool for the
      removal of unwanted antibiotic resistance genes harbored in transposons flanked
      by insertion sequence elements or transposases in lactic acid bacteria used for
      animal and human food production.

PMID- 14660364
TI  - Assessment of an enterovirus sewage surveillance system by comparison of clinical
      isolates with sewage isolates from milwaukee, wisconsin, collected august 1994 to
      december 2002.
AB  - The quantity and serotypes of enteroviruses (EVs) in the influent of a local
      sewage treatment plant were compared to local clinical EV cases to determine if
      testing of sewage is adequate for an EV surveillance system. The study was
      carried out from August 1994 to December 2002. Monthly influent specimens were
      processed by organic flocculation, and dilutions of concentrate were inoculated
      onto a number of different cell types for virus isolation. EVs were detected in
      88 of 100 monthly influent samples. Sewage EV titers were calculated by using
      software provided by the U.S. Environmental Protection Agency for most-probable
      number determination. All 1,068 sewage EV isolates were further grouped
      (echovirus, coxsackievirus B, coxsackievirus A, or poliovirus) by cell culture
      host range analysis (growth pattern of isolates on passage to seven cell lines),
      and 39.0% of the 1,022 EV isolates categorized as non-poliovirus EVs were
      specifically serotyped. For clinical cases, primary virus isolation tests were
      performed on specimens submitted by local hospitals and EV isolates submitted by
      hospitals were serotyped. Clinical EVs were documented for 81 of the 100 months
      studied. In all, 694 EV isolates from clinical cases were serotyped. Annually,
      between 4 and 11 different serotypes of non-poliovirus EVs were identified in
      sewage and from 9 to 19 different non-poliovirus EV serotypes were identified
      from clinical specimens. Usually, the most commonly detected sewage EV serotypes
      were similar to the most commonly detected clinical serotypes; e.g., for 1997,
      echovirus 6 accounted for 53.1% of the typed sewage isolates and 39.4% of the
      clinical infections, while in 1998, echovirus 30 accounted for 50.0 and 46.1%,
      respectively. In 1999, 60.3% of the EVs from clinical cases and 79.7% of the
      sewage isolates were echovirus 11; in 2000, 33.3% of the EVs from clinical cases
      and 40.7% of the sewage isolates were coxsackievirus B5; and in 2001, 44.1% of
      the EVs from clinical cases and 36.2% of the sewage isolates were echovirus 13.
      Annual peaks of both sewage EV titers and clinical cases occurred in late summer
      or early fall. In some years, early spring sewage EVs portended some of the EVs
      that would predominate clinically during the following summer.

PMID- 14660365
TI  - Inoculum size influences bacterial cross contamination between surfaces.
AB  - Many factors have been shown to influence bacterial transfer between surfaces,
      including surface type, bacterial species, moisture level, pressure, and
      friction, but the effect of inoculum size on bacterial transfer has not yet been
      established. Bacterial cross contamination rates during performance of common
      food service tasks were previously determined in our laboratory using nalidixic
      acid-resistant Enterobacter aerogenes. Eight different transfer rates were
      determined, each involving a minimum of 30 volunteers. The influence of source
      inoculum level on the percentage of bacteria transferred (percent transfer rates)
      and log10 CFU per recipient surface was determined using statistical analysis.
      The effect of inoculum size on transfer rate was highly statistically significant
      (P < 0.0001) for all transfer rate data combined (352 observations) and for each
      individual cross contamination rate, except for data on contamination via
      transfer from chicken to hand through a glove barrier (P = 0.1643). Where
      inoculum size on the source was greater, transfer rates were lower, and where
      inoculum size on the source was less, transfer rates were higher. The negative
      linear trend was more obvious for activities that had a larger range of inoculum
      sizes on the source surface. This phenomenon has serious implications for
      research seeking to determine bacterial cross contamination rates, since the
      different transfer efficiencies that were previously shown to be associated with
      certain activities may actually be the result of differing initial inoculum
      levels. The initial inoculum size on the source and the amount of bacteria
      transferred must both be considered to accurately determine bacterial transfer
      rates.

PMID- 14660366
TI  - Functional characterization of a composite bacteriocin locus from malt isolate
      Lactobacillus sakei 5.
AB  - Lactobacillus sakei 5, isolated from malted barley, produces three bacteriocins.
      Genetic and functional analysis of the purified bacteriocins showed that this
      strain produces a plasmid-encoded bacteriocin that is identical to sakacin P, as
      well as two novel, chromosomally encoded bacteriocins, which were designated
      sakacin T and sakacin X. The structural genes specifying sakacin T and sakacin X
      are part of the sakacin TX locus, which consists of two adjacent but divergently
      oriented gene clusters. The first gene cluster includes stxP, stxR, stxK, and
      stxT, which, based on functional and comparative sequence analysis, are believed
      to encode an inducing peptide and proteins involved in regulation and secretion
      of these bacteriocins. The second gene cluster includes the structural and
      immunity genes for sakacin T, a class IIb two-peptide bacteriocin composed of
      SakTalpha and SakTbeta, and sakacin X, a class IIa bacteriocin. Interestingly, a
      so-called transport accessory protein was absent from the locus, and based on our
      results it appears that a dedicated accessory protein is not required for
      processing and transport of sakacin T and sakacin X.

PMID- 14660367
TI  - Bacterial synergism or antagonism in a gel cassette system.
AB  - The growth and the metabolic activity of Shewanella putrfaciens, Brochothrix
      thermosphacta, and Pseudomonas sp., when cultured individually or in all possible
      combinations in gel cassettes system supplemented with 0.1% glucose at 5 degrees
      C, were investigated. The overall outcome was that the coexistence of the above
      mentioned microorganisms affected not only each growth rate but also their type
      of metabolic end products compared to the control cultures. These effects were
      varied and depended on the selection of the combination of the tested bacteria.
      For example, the growth of Pseudomonas sp. strains cocultured with either B.
      thermosphacta or S. putrefaciens strains resulted in different effects: a
      promoting one for the first and an inhibitory one for the second. Moreover, the
      production of formic acid and two unidentified organic acids (peaks a and b) was
      characteristic in all cases in which S. putrefaciens was cultured.

PMID- 14660368
TI  - Laboratory cultivation of widespread and previously uncultured soil bacteria.
AB  - Most soil bacteria belong to family-level phylogenetic groups with few or no
      known cultivated representatives. We cultured a collection of 350 isolates from
      soil by using simple solid media in petri dishes. These isolates were assigned to
      60 family-level groupings in nine bacterial phyla on the basis of a comparative
      analysis of their 16S rRNA genes. Ninety-three (27%) of the isolates belonged to
      20 as-yet-unnamed family-level groupings, many from poorly studied bacterial
      classes and phyla. They included members of subdivisions 1, 2, 3, and 4 of the
      phylum Acidobacteria, subdivision 3 of the phylum Verrucomicrobia, subdivision 1
      of the phylum Gemmatimonadetes, and subclasses Acidimicrobidae and
      Rubrobacteridae of the phylum ACTINOBACTERIA: In addition, members of 10 new
      family-level groupings of subclass Actinobacteridae of the phylum Actinobacteria
      and classes Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria of
      the phylum Proteobacteria were obtained. The high degree of phylogenetic novelty
      and the number of isolates affiliated with so-called unculturable groups show
      that simple cultivation methods can still be developed further to obtain
      laboratory cultures of many phylogenetically novel soil bacteria.

PMID- 14660369
TI  - Diversity of bacteria associated with natural aphid populations.
AB  - The bacterial communities of aphids were investigated by terminal restriction
      fragment length polymorphism and denaturing gradient gel electrophoresis analysis
      of 16S rRNA gene fragments generated by PCR with general eubacterial primers. By
      both methods, the gamma-proteobacterium Buchnera was detected in laboratory
      cultures of six parthenogenetic lines of the pea aphid Acyrthosiphon pisum and
      one line of the black bean aphid Aphis fabae, and one or more of four previously
      described bacterial taxa were also detected in all aphid lines except one of A.
      pisum. These latter bacteria, collectively known as secondary symbionts or
      accessory bacteria, comprised three taxa of gamma-proteobacteria (R-type [PASS],
      T-type [PABS], and U-type [PAUS]) and a rickettsia (S-type [PAR]). Complementary
      analysis of aphids from natural populations of four aphid species (A. pisum [n =
      74], Amphorophora rubi [n = 109], Aphis sarothamni [n = 42], and Microlophium
      carnosum [n = 101]) from a single geographical location revealed Buchnera and up
      to three taxa of accessory bacteria, but no other bacterial taxa, in each aphid.
      The prevalence of accessory bacterial taxa varied significantly among aphid
      species but not with the sampling month (between June and August 2000). These
      results indicate that the accessory bacterial taxa are distributed across
      multiple aphid species, although with variable prevalence, and that laboratory
      culture does not generally result in a shift in the bacterial community in
      aphids. Both the transmission patterns of the accessory bacteria between
      individual aphids and their impact on aphid fitness are suggested to influence
      the prevalence of accessory bacterial taxa in natural aphid populations.

PMID- 14660370
TI  - Microbial communities associated with geological horizons in coastal subseafloor
      sediments from the sea of okhotsk.
AB  - Microbial communities from a subseafloor sediment core from the southwestern Sea
      of Okhotsk were evaluated by performing both cultivation-dependent and
      cultivation-independent (molecular) analyses. The core, which extended 58.1 m
      below the seafloor, was composed of pelagic clays with several volcanic ash
      layers containing fine pumice grains. Direct cell counting and quantitative PCR
      analysis of archaeal and bacterial 16S rRNA gene fragments indicated that the
      bacterial populations in the ash layers were approximately 2 to 10 times larger
      than those in the clays. Partial sequences of 1,210 rRNA gene clones revealed
      that there were qualitative differences in the microbial communities from the two
      different types of layers. Two phylogenetically distinct archaeal assemblages in
      the Crenarchaeota, the miscellaneous crenarchaeotic group and the deep-sea
      archaeal group, were the most predominant archaeal 16S rRNA gene components in
      the ash layers and the pelagic clays, respectively. Clones of 16S rRNA gene
      sequences from members of the gamma subclass of the class Proteobacteria
      dominated the ash layers, whereas sequences from members of the candidate
      division OP9 and the green nonsulfur bacteria dominated the pelagic clay
      environments. Molecular (16S rRNA gene sequence) analysis of 181 isolated
      colonies revealed that there was regional proliferation of viable heterotrophic
      mesophiles in the volcanic ash layers, along with some gram-positive bacteria and
      actinobacteria. The porous ash layers, which ranged in age from tens of thousands
      of years to hundreds of thousands of years, thus appear to be discrete microbial
      habitats within the coastal subseafloor clay sediment, which are capable of
      harboring microbial communities that are very distinct from the communities in
      the more abundant pelagic clays.

PMID- 14660371
TI  - Targeting methanopterin biosynthesis to inhibit methanogenesis.
AB  - This paper describes the design, synthesis, and successful employment of
      inhibitors of 4-(beta-D-ribofuranosyl)aminobenzene-5'-phosphate (RFA-P) synthase,
      which catalyzes the first committed step in the biosynthesis of methanopterin, to
      specifically halt the growth of methane-producing microbes. RFA-P synthase
      catalyzes the first step in the synthesis of tetrahydromethanopterin, a key
      cofactor required for methane formation and for one-carbon transformations in
      methanogens. A number of inhibitors, which are N-substituted derivatives of p
      aminobenzoic acid (pABA), have been synthesized and their inhibition constants
      with RFA-P synthase have been determined. Based on comparisons of the inhibition
      constants among various inhibitors, we propose that the pABA binding site in RFA
      P synthase has a relatively large hydrophobic pocket near the amino group. These
      enzyme-targeted inhibitors arrest the methanogenesis and growth of pure cultures
      of methanogens. Supplying pABA to the culture relieves the inhibition, indicating
      a competitive interaction between pABA and the inhibitor at the cellular target,
      which is most likely RFAP synthase. The inhibitors do not adversely affect the
      growth of pure cultures of the bacteria (acetogens) that play a beneficial role
      in the rumen. Inhibitors added to dense ruminal fluid cultures (artificial
      rumena) halt methanogenesis; however, they do not inhibit volatile fatty acid
      (VFA) production and, in some cases, VFA levels are slightly elevated in the
      methanogenesis-inhibited cultures. We suggest that inhibiting methanopterin
      biosynthesis could be considered in strategies to decrease anthropogenic methane
      emissions, which could have an environmental benefit since methane is a potent
      greenhouse gas.

PMID- 14660372
TI  - Transduction of porcine enteropathogenic Escherichia coli with a derivative of a
      shiga toxin 2-encoding bacteriophage in a porcine ligated ileal loop system.
AB  - In this study, we have investigated the ability of detoxified Shiga toxin (Stx)
      converting bacteriophages Phi3538 (Deltastx(2)::cat) (H. Schmidt et al., Appl.
      Environ. Microbiol. 65:3855-3861, 1999) and H-19B::Tn10d-bla (D. W. Acheson et
      al., Infect. Immun. 66:4496-4498, 1998) to lysogenize enteropathogenic
      Escherichia coli (EPEC) strains in vivo. We were able to transduce the porcine
      EPEC strain 1390 (O45) with Phi3538 (Deltastx(2)::cat) in porcine ligated ileal
      loops but not the human EPEC prototype strain E2348/69 (O127). Neither strain
      1390 nor strain E2348/69 was lysogenized under these in vivo conditions when E.
      coli K-12 containing H-19B::Tn10d-bla was used as the stx1 phage donor. The
      repeated success in the in vivo transduction of an Stx2-encoding phage to a
      porcine EPEC strain in pig loops was in contrast to failures in the in vitro
      trials with these and other EPEC strains. These results indicate that in vivo
      conditions are more effective for transduction of Stx2-encoding phages than in
      vitro conditions.

PMID- 14660373
TI  - Specific and sensitive detection of Ralstonia solanacearum in soil on the basis
      of PCR amplification of fliC fragments.
AB  - Ralstonia solanacearum is the causative agent of bacterial wilt in many important
      crops. A specific and sensitive PCR detection method that uses primers targeting
      the gene coding for the flagella subunit, fliC, was established. Based on the
      first fliC gene sequence of R. solanacearum strain K60 available at GenBank, the
      Ral_fliC PCR primer system was designed; this system yielded a single 724-bp
      product with the DNAs of all of the R. solanacearum strains tested. However, R.
      pickettii and four environmental Ralstonia isolates also yielded amplicons. The
      Ral_fliC PCR products obtained with 12 strains (R. solanacearum, R. pickettii,
      and environmental isolates) were sequenced. By sequence alignment, Rsol_fliC
      primers specific for R. solanacearum were designed. With this primer system, a
      specific 400-bp PCR product was obtained from all 82 strains of R. solanacearum
      tested. Six strains of R. pickettii and several closely related environmental
      isolates yielded no PCR product; however, a product was obtained with one
      Pseudomonas syzygii strain. A GC-clamped 400-bp fliC product could be separated
      in denaturing gradient gels and allowed us to distinguish P. syzygii from R.
      solanacearum. The Rsol_fliC PCR system was applied to detect R. solanacearum in
      soil. PCR amplification, followed by Southern blot hybridization, allowed us to
      detect about one target DNA molecule per PCR, which is equivalent to 10(3) CFU g
      of bulk soil(-1). The system was applied to survey soils from different
      geographic origins for the presence of R. solanacearum.

PMID- 14660374
TI  - Molecular and culture-based analyses of aerobic carbon monoxide oxidizer
      diversity.
AB  - Isolates belonging to six genera not previously known to oxidize CO were obtained
      from enrichments with aquatic and terrestrial plants. DNA from these and other
      isolates was used in PCR assays of the gene for the large subunit of carbon
      monoxide dehydrogenase (coxL). CoxL and putative coxL fragments were amplified
      from known CO oxidizers (e.g., Oligotropha carboxidovorans and Bradyrhizobium
      japonicum), from novel CO-oxidizing isolates (e.g., Aminobacter sp. strain COX,
      Burkholderia sp. strain LUP, Mesorhizobium sp. strain NMB1, Stappia strains M4
      and M8, Stenotrophomonas sp. strain LUP, and Xanthobacter sp. strain COX), and
      from several well-known isolates for which the capacity to oxidize CO is reported
      here for the first time (e.g., Burkholderia fungorum LB400, Mesorhizobium loti,
      Stappia stellulata, and Stappia aggregata). PCR products from several taxa, e.g.,
      O. carboxidovorans, B. japonicum, and B. fungorum, yielded sequences with a high
      degree (>99.6%) of identity to those in GenBank or genome databases. Aligned
      sequences formed two phylogenetically distinct groups. Group OMP contained
      sequences from previously known CO oxidizers, including O. carboxidovorans and
      Pseudomonas thermocarboxydovorans, plus a number of closely related sequences.
      Group BMS was dominated by putative coxL sequences from genera in the
      Rhizobiaceae and other alpha-PROTEOBACTERIA: PCR analyses revealed that many CO
      oxidizers contained two coxL sequences, one from each group. CO oxidation by M.
      loti, for which whole-genome sequencing has revealed a single BMS-group putative
      coxL gene, strongly supports the notion that BMS sequences represent functional
      CO dehydrogenase proteins that are related to but distinct from previously
      characterized aerobic CO dehydrogenases.

PMID- 14660375
TI  - Uptake of carbon monoxide and hydrogen at environmentally relevant concentrations
      by mycobacteria.
AB  - Liquid culture assays revealed a previously unreported capacity for Mycobacterium
      bovis BCG, M. gordonae, and M. marinum to oxidize CO and for M. smegmatis to
      consume molecular hydrogen. M. bovis BCG, M. gordonae, M. smegmatis, and M.
      tuberculosis H37Ra oxidized CO at environmentally relevant concentrations (<50
      ppm); H2 oxidation by M. gordonae and M. smegmatis also occurred at
      environmentally relevant concentrations (<10 ppm). CO was not consumed by M.
      avium or M. microti, although the latter appeared to possess CO dehydrogenase
      (CODH) genes based on PCR results with primers designed for the CODH large
      subunit, coxL. M. smegmatis and M. gordonae oxidized CO under suboxic (10 and 1%
      atmospheric oxygen) and anoxic conditions in the presence of nitrate; no
      oxidation occurred under anoxic conditions without nitrate. Similar results were
      obtained for H2 oxidation by M. smegmatis. Phylogenetic analyses of coxL PCR
      products indicated that mycobacterial sequences form a subclade distinct from
      that of other bacterial coxL, with limited differentiation among fast- and slow
      growing strains.

PMID- 14660376
TI  - Characterization of the argA gene required for arginine biosynthesis and
      syringomycin production by Pseudomonas syringae pv. syringae.
AB  - Two types of necrosis-inducing lipodepsipeptide toxins, called syringomycin and
      syringopeptin, are major virulence factors of Pseudomonas syringae pv. syringae
      strain B301D. A previous study showed that a locus, called syrA, was required for
      both syringomycin production and plant pathogenicity, and the syrA locus was
      speculated to encode a regulator of toxin production. In this study, sequence
      analysis of the 8-kb genomic DNA fragment that complements the syrA phenotype
      revealed high conservation among a broad spectrum of fluorescent pseudomonads.
      The putative protein encoded by open reading frame 4 (ORF4) (1,299 bp) in the
      syrA locus region exhibited 85% identity to ArgA, which is involved in arginine
      biosynthesis in Pseudomonas aeruginosa. Growth of strain W4S2545, the syrA
      mutant, required supplementation of N minimal medium with arginine. Similarly,
      syringomycin production of syrA mutant W4S2545 was restored by the addition of
      arginine to culture media. Furthermore, the insertion of Tn5 in the genome of the
      syrA mutant W4S2545 was localized between nucleotides 146 and 147 in ORF4, and
      syringomycin production was complemented in trans with the wild-type DNA fragment
      containing intact ORF4. These results demonstrate that the syrA locus is the argA
      gene of P. syringae pv. syringae and that argA is directly involved in arginine
      biosynthesis and therefore indirectly affects syringomycin production because of
      arginine deficiency.

PMID- 14660377
TI  - Ability of Lactococcus lactis to export viral capsid antigens: a crucial step for
      development of live vaccines.
AB  - The food grade bacterium Lactococcus lactis is a potential vehicle for protein
      delivery in the gastrointestinal tract. As a model, we constructed lactococcal
      strains producing antigens of infectious bursal disease virus (IBDV). IBDV
      infects chickens and causes depletion of B-lymphoid cells in the bursa of
      Fabricius and subsequent immunosuppression, morbidity, or acute mortality. The
      two major IBDV antigens, i.e., VP2 and VP3, that form the viral capsid were
      expressed and targeted to the cytoplasm, the cell wall, or the extracellular
      compartment of L. lactis. Whereas VP3 was successfully targeted to the three
      compartments by the use of relevant expression and export vectors, VP2 was
      recalcitrant to export, thus confirming the difficulty of translocating naturally
      nonsecreted proteins across the bacterial membrane. This defect could be partly
      overcome by fusing VP2 to a naturally secreted protein (the staphylococcal
      nuclease Nuc) that carried VP2 through the membrane. Lactococcal strains
      producing Nuc-VP2 and VP3 in various bacterial compartments were administered
      orally to chickens. The chickens did not develop any detectable immune response
      against VP2 and VP3 but did exhibit an immune response against Nuc when Nuc-VP2
      was anchored to the cell wall of lactococci.

PMID- 14660378
TI  - Quantitative real-time PCR for determination of microcystin synthetase e copy
      numbers for microcystis and anabaena in lakes.
AB  - Cyanobacterial mass occurrences in freshwater lakes are generally formed by
      Anabaena, Microcystis, and Planktothrix, which may produce cyclic heptapeptide
      hepatotoxins, microcystins. Thus far, identification of the most potent
      microcystin producer in a lake has not been possible due to a lack of
      quantitative methods. The aim of this study was to identify the microcystin
      producing genera and to determine the copy numbers of microcystin synthetase gene
      E (mcyE) in Lake Tuusulanjarvi and Lake Hiidenvesi in Finland by quantitative
      real-time PCR. The microcystin concentrations and cyanobacterial cell densities
      of these lakes were also determined. The microcystin concentrations correlated
      positively with the sum of Microcystis and Anabaena mcyE copy numbers from both
      Lake Tuusulanjarvi and Lake Hiidenvesi, indicating that mcyE gene copy numbers
      can be used as surrogates for hepatotoxic Microcystis and ANABAENA: The main
      microcystin producer in Lake Tuusulanjarvi was Microcystis spp., since average
      Microcystis mcyE copy numbers were >30 times more abundant than those of
      ANABAENA: Lake Hiidenvesi seemed to contain both nontoxic and toxic Anabaena as
      well as toxic Microcystis strains. Identifying the most potent microcystin
      producer in a lake could be valuable for designing lake restoration strategies,
      among other uses.

PMID- 14660379
TI  - Metagenome survey of biofilms in drinking-water networks.
AB  - Most naturally occurring biofilms contain a vast majority of microorganisms which
      have not yet been cultured, and therefore we have little information on the
      genetic information content of these communities. Therefore, we initiated work to
      characterize the complex metagenome of model drinking water biofilms grown on
      rubber-coated valves by employing three different strategies. First, a sequence
      analysis of 650 16S rRNA clones indicated a high diversity within the biofilm
      communities, with the majority of the microbes being closely related to the
      Proteobacteria: Only a small fraction of the 16S rRNA sequences were highly
      similar to rRNA sequences from Actinobacteria, low-G+C gram-positives and the
      Cytophaga-Flavobacterium-Bacteroides group. Our second strategy included a
      snapshot genome sequencing approach. Homology searches in public databases with
      5,000 random sequence clones from a small insert library resulted in the
      identification of 2,200 putative protein-coding sequences, of which 1,026 could
      be classified into functional groups. Similarity analyses indicated that
      significant fractions of the genes and proteins identified were highly similar to
      known proteins observed in the genera Rhizobium, Pseudomonas, and Escherichia:
      Finally, we report 144 kb of DNA sequence information from four selected cosmid
      clones, of which two formed a 75-kb overlapping contig. The majority of the
      proteins identified by whole-cosmid sequencing probably originated from microbes
      closely related to the alpha-, beta-, and gamma-Proteobacteria: The sequence
      information was used to set up a database containing the phylogenetic and genomic
      information on this model microbial community. Concerning the potential health
      risk of the microbial community studied, no DNA or protein sequences directly
      linked to pathogenic traits were identified.

PMID- 14660380
TI  - Seasonal changes in the rhizosphere microbial communities associated with field
      grown genetically modified canola (Brassica napus).
AB  - The introduction of transgenic plants into agricultural ecosystems has raised the
      question of the ecological impact of these plants on nontarget organisms, such as
      soil bacteria. Although differences in both the genetic structure and the
      metabolic function of the microbial communities associated with some transgenic
      plant lines have been established, it remains to be seen whether these
      differences have an ecological impact on the soil microbial communities. We
      conducted a 2-year, multiple-site field study in which rhizosphere samples
      associated with a transgenic canola variety and a conventional canola variety
      were sampled at six times throughout the growing season. The objectives of this
      study were to identify differences between the rhizosphere microbial community
      associated with the transgenic plants and the rhizosphere microbial community
      associated with the conventional canola plants and to determine whether the
      differences were permanent or depended on the presence of the plant. Community
      level physiological profiles, fatty acid methyl ester profiles, and terminal
      amplified ribosomal DNA restriction analysis profiles of rhizosphere microbial
      communities were compared to the profiles of the microbial community associated
      with an unplanted, fallow field plot. Principal-component analysis showed that
      there was variation in the microbial community associated with both canola
      variety and growth season. Importantly, while differences between the microbial
      communities associated with the transgenic plant variety were observed at several
      times throughout the growing season, all analyses indicated that when the
      microbial communities were assessed after winter, there were no differences
      between microbial communities from field plots that contained harvested
      transgenic canola plants and microbial communities from field plots that did not
      contain plants during the field season. Hence, the changes in the microbial
      community structure associated with genetically modified plants were temporary
      and did not persist into the next field season.

PMID- 14660381
TI  - Use of a green fluorescent strain for analysis of Xylella fastidiosa colonization
      of Vitis vinifera.
AB  - Xylella fastidiosa causes Pierce's disease of grapevine as well as several other
      major agricultural diseases but is a benign endophyte in most host plants. X.
      fastidiosa colonizes the xylem vessels of host plants and is transmitted by xylem
      sap-feeding insect vectors. To understand better the pattern of host colonization
      and its relationship to disease, we engineered X. fastidiosa to express a green
      fluorescent protein (Gfp) constitutively and performed confocal laser-scanning
      microscopic analysis of colonization in a susceptible host, Vitis vinifera. In
      symptomatic leaves, the fraction of vessels colonized by X. fastidiosa was
      fivefold higher than in nearby asymptomatic leaves. The fraction of vessels
      completely blocked by X. fastidiosa colonies increased 40-fold in symptomatic
      leaves and was the feature of colonization most dramatically linked to symptoms.
      Therefore, the extent of vessel blockage by bacterial colonization is highly
      likely to be a crucial variable in symptom expression. Intriguingly, a high
      proportion (>80%) of colonized vessels were not blocked in infected leaves and
      instead had small colonies or solitary cells, suggesting that vessel blockage is
      not a colonization strategy employed by the pathogen but, rather, a by-product of
      endophytic colonization. We present evidence for X. fastidiosa movement through
      bordered pits to neighboring vessels and propose that vessel-to-vessel movement
      is a key colonization strategy whose failure results in vessel plugging and
      disease.

PMID- 14660382
TI  - In vitro and in vivo studies of the Yrp1 protease from Yersinia ruckeri and its
      role in protective immunity against enteric red mouth disease of salmonids.
AB  - Yersinia ruckeri, the etiological agent of the enteric red mouth disease (ERM) of
      salmonids, produces Yrp1, a serralysin metalloprotease involved in pathogenesis.
      We describe here the hydrolytic and immunogenic properties of Yrp1. The protease
      was able to hydrolyze different matrix and muscle proteins as laminin,
      fibrinogen, gelatine, actin, and myosin but not type II and IV collagens. In
      addition, the Yrp1 protein, when inactivated by heat and used as an immunogen,
      was able to elicit a strong protection against the development of ERM. The
      analysis of different Y. ruckeri strains with (Azo+) or without (Azo-) Yrp1
      activity showed that all of them contained the yrp1 operon. By using yrp1::lacZ
      operon fusions, protease production analysis, and complementation studies, it was
      possible to show that an Azo- strain was blocked at the transcription level. The
      transcriptional study of the yrp1 operon under different environmental conditions
      showed that it was regulated by osmolarity and temperature, without pH influence.
      Finally, when beta-galactosidase activity was used as a probe in vivo, the
      progression of the disease in the fish could be visualized, and the tropism of
      the bacterium and affected organs could be defined. This system opens a vast
      field of study not only with regard to fish disease progression but also in
      pathogen interactions, temporal gene expression, carrier stages, antibiotic
      resistance selection, etc.

PMID- 14660383
TI  - Variation in biofilm formation among strains of Listeria monocytogenes.
AB  - Contamination of food by Listeria monocytogenes is thought to occur most
      frequently in food-processing environments where cells persist due to their
      ability to attach to stainless steel and other surfaces. Once attached these
      cells may produce multicellular biofilms that are resistant to disinfection and
      from which cells can become detached and contaminate food products. Because there
      is a correlation between virulence and serotype (and thus phylogenetic division)
      of L. monocytogenes, it is important to determine if there is a link between
      biofilm formation and disease incidence for L. monocytogenes. Eighty L.
      monocytogenes isolates were screened for biofilm formation to determine if there
      is a robust relationship between biofilm formation, phylogenic division, and
      persistence in the environment. Statistically significant differences were
      detected between phylogenetic divisions. Increased biofilm formation was observed
      in Division II strains (serotypes 1/2a and 1/2c), which are not normally
      associated with food-borne outbreaks. Differences in biofilm formation were also
      detected between persistent and nonpersistent strains isolated from bulk milk
      samples, with persistent strains showing increased biofilm formation relative to
      nonpersistent strains. There were no significant differences detected among
      serotypes. Exopolysaccharide production correlated with cell adherence for high
      biofilm-producing strains. Scanning electron microscopy showed that a high
      biofilm-forming strain produced a dense, three-dimensional structure, whereas a
      low-biofilm-forming strain produced a thin, patchy biofilm. These data are
      consistent with data on persistent strains forming biofilms but do not support a
      consistent relationship between enhanced biofilm formation and disease incidence.

PMID- 14660384
TI  - Concomitant induction of systemic resistance to Pseudomonas syringae pv.
      lachrymans in cucumber by Trichoderma asperellum (T-203) and accumulation of
      phytoalexins.
AB  - Most studies on the reduction of disease incidence in soil treated with
      Trichoderma asperellum have focused on microbial interactions rather than on
      plant responses. This study presents conclusive evidence for the induction of a
      systemic response against angular leaf spot of cucumber (Pseudomonas syringae pv.
      lachrymans) following application of T. asperellum to the root system. To
      ascertain that T. asperellum was the only microorganism present in the root
      milieu, plants were grown in an aseptic hydroponic growth system. Disease
      symptoms were reduced by as much as 80%, corresponding to a reduction of 2 orders
      of magnitude in bacterial cell densities in leaves of plants pretreated with T.
      asperellum. As revealed by electron microscopy, bacterial cell proliferation in
      these plants was halted. The protection afforded by the biocontrol agent was
      associated with the accumulation of mRNA of two defense genes: the
      phenylpropanoid pathway gene encoding phenylalanine ammonia lyase (PAL) and the
      lipoxygenase pathway gene encoding hydroxyperoxide lyase (HPL). This was further
      supported by the accumulation of secondary metabolites of a phenolic nature that
      showed an increase of up to sixfold in inhibition capacity of bacterial growth in
      vitro. The bulk of the antimicrobial activity was found in the acid-hydrolyzed
      extract containing the phenolics in their aglycone form. High-performance liquid
      chromatography analysis of phenolic compounds showed a marked change in their
      profile in the challenged, preelicited plants relative to that in challenged
      controls. The results suggest that similar to beneficial rhizobacteria, T.
      asperellum may activate separate metabolic pathways in cucumber that are involved
      in plant signaling and biosynthesis, eventually leading to the systemic
      accumulation of phytoalexins.

PMID- 14660386
TI  - Construction of otherwise isogenic serotype 6B, 7F, 14, and 19F capsular variants
      of Streptococcus pneumoniae strain TIGR4.
AB  - The polysaccharide capsule is the primary virulence factor in Streptococcus
      pneumoniae. There are at least 90 serotypes of S. pneumoniae, identified based on
      the immunogenicity of different capsular sugars. The aim of this study was to
      construct pneumococcal strains that are isogenic except for capsular type.
      Serotype 4 strain TIGR4 was rendered unencapsulated by recombinational
      replacement of the capsular polysaccharide synthesis (cps) locus with the
      bicistronic Janus cassette (C. K. Sung, J. P. Claverys, and D. A. Morrison, Appl.
      Environ. Microbiol. 67:5190-5196, 2001). In subsequent transformation with
      chromosomal DNA, the cassette was replaced by the cps locus derived from a strain
      of a different serotype, either 6B, 7F, 14, or 19F. To minimize the risk of
      uncontrolled recombinational replacements in loci other than cps, the
      TIGRcps::Janus strain was "backcross" transformed three times with chromosomal
      DNA of subsequently constructed capsular type transformants. Capsular serotypes
      were confirmed in all new capsule variants by the Quellung reaction. Restriction
      fragment length polymorphism (RFLP) analysis of the cps locus confirmed the
      integrity of the cps region transformed into the TIGR strain, and RFLP of the
      flanking regions confirmed their identities with the corresponding regions of the
      recipient. Transformants had in vitro growth rates greater than or equal to that
      of TIGR4. All four strains were able to colonize C57BL/6 mice (female, 6 weeks
      old) for at least 7 days when mice were intranasally inoculated with 6 x 10(6) to
      8 x 10(6) CFU. The constructed capsular variants of TIGR4 are suitable for use in
      studies on the role of S. pneumoniae capsular polysaccharide in immunity,
      colonization, and pathogenesis.

PMID- 14660385
TI  - Molecular evidence for novel planctomycete diversity in a municipal wastewater
      treatment plant.
AB  - We examined anoxic and aerobic basins and an anaerobic digestor of a municipal
      wastewater treatment plant for the presence of novel planctomycete-like
      diversity. Three 16S rRNA gene libraries were constructed by using a 16S rRNA
      targeted universal reverse primer and a forward PCR primer specific for
      Planctomyces: Phylogenetic analysis of 234 16S rRNA gene sequences defined 110
      operational taxonomic units. The majority of these sequences clustered with the
      four known genera, Pirellula (32%), Planctomyces (18.4%), Gemmata (3.8%), and
      Isosphaera (0.4%). More interestingly, 42.3% of the sequences appeared to define
      two distantly separated monophyletic groups. The first group, represented by
      35.5% of the sequences, was related to the Planctomyces group and branched as a
      monophyletic cluster. It exhibited between 11.9 and 20.3% 16S rRNA gene sequence
      dissimilarity in comparisons with cultivated planctomycetes. The second group,
      represented by 6.8% of the sequences, was deeply rooted within the
      Planctomycetales tree. It was distantly related to the anammox sequences (level
      of dissimilarity, 20.3 to 24.4%) and was a monophyletic cluster. The retrieved
      sequences extended the intralineage phylogenetic depth of the Plantomycetales
      from 23 to 30.6%. The lineages described here may have a broad diversity of
      undiscovered biochemical and metabolic novelty. We developed a new 16S rRNA
      targeted oligonucleotide probe and localized members of one of the phylogenetic
      groups using the fluorescent in situ hybridization technique. Our results
      indicate that activated sludge contains very diverse representatives of this
      group, which grow under aerobic and anoxic conditions and even under anaerobic
      conditions. The majority of species in this group remain poorly characterized.

PMID- 14660387
TI  - Effects of saxitoxin (STX) and veratridine on bacterial Na+ -K+ fluxes: a
      prokaryote-based STX bioassay.
AB  - Saxitoxin (STX) is a potent natural sodium channel blocker and represents a
      significant health concern worldwide. We describe here the antagonistic effects
      of STX and veratridine (VTD), an Na+ channel activator, on three gram-negative
      bacteria and their application to an STX bioassay. STX reduced the total cellular
      levels of both Na+ and K+, as measured by flame photometry, whereas VTD increased
      the cellular concentrations relative to control ion fluxes in the cyanobacterium
      Cylindrospermopsis raciborskii AWT205. Endogenous STX production in toxic
      cyanobacterial strains of C. raciborskii and Anabaena circinalis prevented cell
      lysis induced by VTD stress. Microscopic cell counts showed that non-STX
      producing cyanobacteria displayed complete cell lysis and trichome fragmentation
      5 to 8 h after addition of VTD and vanadate (VAN), an inhibitor of sodium pumps.
      The addition of STX, or its analogue neoSTX, prior to treatment with VTD plus VAN
      prevented complete lysis in non-STX-producing cyanobacteria. VTD also affected
      cyanobacterial metabolism, and the presence of exogenous STX in the sample also
      ameliorated this decrease in metabolic activity, as measured by the cellular
      conversion of tetrazolium into formazan. Reduced primary metabolism was also
      recorded as a decrease in the light emissions of Vibrio fischeri exposed to VTD.
      Addition of STX prior to VTD resulted in a rapid and dose-dependent response to
      the presence of the channel blocker, with samples exhibiting resistance to the
      VTD effect. Our findings demonstrate that STX and VTD influence bacterial Na+ and
      K+ fluxes in opposite ways, and these principles can be applied to the
      development of a prokaryote-based STX bioassay.

PMID- 14660388
TI  - Detection of infectious adenovirus in cell culture by mRNA reverse transcription
      PCR.
AB  - We have developed and evaluated the reverse transcription (RT)-PCR detection of
      mRNA in cell culture to assay infectious adenoviruses (Ads) by using Ad type 2
      (Ad2) and Ad41 as models. Only infectious Ads are detected because they are the
      only ones able to produce mRNA during replication in cell culture. Three primer
      sets for RT-PCR amplification of mRNA were evaluated for their sensitivity and
      specificity: a conserved region of late mRNA transcript encoding a virion
      structural hexon protein and detecting a wide range of human Ads and two primer
      sets targeting a region of an early mRNA transcript that specifically detects
      either Ad2 and Ad5 or Ad40 and Ad41. The mRNAs of infected A549 and Graham 293
      cells were recovered from cell lysates with oligo(dT) at different time periods
      after infection and treated with RNase-free DNase to remove residual
      contaminating DNA, and then Ad mRNA was detected by RT-PCR assay. The mRNA of Ad2
      was detected as early as 6 h after infection at 10(6) infectious units (IU) per
      cell culture and after longer incubation times at levels as low as 1 to 2 IU per
      cell culture. The mRNA of Ad41 was detected as soon as 24 h after infection at
      10(6) IU per cell culture and at levels as low as 5 IU per cell culture after
      longer incubation times. To confirm the detection of only infectious viruses, it
      was shown that no mRNA was detected from Ad2 and Ad41 inactivated by free
      chlorine or high doses of collimated, monochromatic (254-nm) UV radiation.
      Detection of Ad2 mRNA exactly coincided with the presence of virus infectivity
      detected by cytopathogenic effects in cell cultures, but mRNA detection occurred
      sooner. These results suggest that mRNA detection by RT-PCR assay in inoculated
      cell cultures is a very sensitive, specific, and rapid method by which to detect
      infectious Ads in water and other environmental samples.

PMID- 14660389
TI  - Cometabolism of methyl tertiary butyl ether and gaseous n-alkanes by Pseudomonas
      mendocina KR-1 grown on C5 to C8 n-alkanes.
AB  - Pseudomonas mendocina KR-1 grew well on toluene, n-alkanes (C5 to C8), and 1
      degrees alcohols (C2 to C8) but not on other aromatics, gaseous n-alkanes (C1 to
      C4), isoalkanes (C4 to C6), 2 degrees alcohols (C3 to C8), methyl tertiary butyl
      ether (MTBE), or tertiary butyl alcohol (TBA). Cells grown under carbon-limited
      conditions on n-alkanes in the presence of MTBE (42 micromoles) oxidized up to
      94% of the added MTBE to TBA. Less than 3% of the added MTBE was oxidized to TBA
      when cells were grown on either 1 degrees alcohols, toluene, or dextrose in the
      presence of MTBE. Concentrated n-pentane-grown cells oxidized MTBE to TBA without
      a lag phase and without generating tertiary butyl formate (TBF) as an
      intermediate. Neither TBF nor TBA was consumed by n-pentane-grown cells, while
      formaldehyde, the expected C1 product of MTBE dealkylation, was rapidly consumed.
      Similar Ks values for MTBE were observed for cells grown on C5 to C8 n-alkanes
      (12.95 +/- 2.04 mM), suggesting that the same enzyme oxidizes MTBE in cells grown
      on each n-alkane. All growth-supporting n-alkanes (C5 to C8) inhibited MTBE
      oxidation by resting n-pentane-grown cells. Propane (Ki = 53 micromoles) and n
      butane (Ki = 16 micromoles) also inhibited MTBE oxidation, and both gases were
      also consumed by cells during growth on n-pentane. Cultures grown on C5 to C8 n
      alkanes also exhibited up to twofold-higher levels of growth in the presence of
      propane or n-butane, whereas no growth stimulation was observed with methane,
      ethane, MTBE, TBA, or formaldehyde. The results are discussed in terms of their
      impacts on our understanding of MTBE biodegradation and cometabolism.

PMID- 14660390
TI  - Application of a specific and sensitive radiometric assay for microbial lipase
      activities in marine water samples from the lagoon of noumea.
AB  - Marine microbiologists commonly assay lipase activities by using a synthetic
      fluorescent analog, 4-methylumbelliferyl (MUF)-oleate. The technique is
      convenient, but it is considered to be unspecific because of the structure of
      this analog. This study reports the design of a new specific and sensitive lipase
      assay based on the use of a radiolabeled triglyceride, [3H]triolein. Free fatty
      acids (FFA) resulting from its hydrolysis are isolated as a function of time in a
      one-step liquid-liquid extraction and then radioassayed. MUF-oleate and
      [3H]triolein techniques were compared by measuring lipase activities at similar
      substrate concentrations along a trophic gradient in the Southwest Lagoon of New
      Caledonia, near Noumea. Hydrolysis rates decreased from the nearshore station to
      the offshore station and showed similar trends regardless of the technique used.
      Rates decreased from 5.83 to 0.88 nmol of FFA. liter-1. h-1 and from 0.76 to 0.23
      nmol of 3H-FFA. liter-1. h-1, respectively. These results appeared to be
      consistent with bacterial production results, which also decreased similarly
      (from 0.59 to 0.26 micrograms of C. liter-1. h-1). However, the ratio of MUF
      oleate activities to [3H]triolein activities, which was constant at the offshore
      stations (3.8 +/- 0.1), gradually increased at the nearshore stations (from 4.1
      to 7.6). This result shows that the two assays respond in different ways to
      changes in environmental conditions and validates the need to set up more
      specific enzymatic assays.

PMID- 14660391
TI  - Transporter-mediated uptake of 2-chloro- and 2-hydroxybenzoate by Pseudomonas
      huttiensis strain D1.
AB  - We investigated the mechanisms of uptake of 2-chlorobenzoate (2-CBa) and 2
      hydroxybenzoate (2-HBa) by Pseudomonas huttiensis strain D1. Uptake was monitored
      by assaying intracellular accumulation of 2-[UL-ring-14C]CBa and 2-[UL-ring
      14C]HBa. Uptake of 2-CBa showed substrate saturation kinetics with an apparent Km
      of 12.7 +/- 2.6 micromoles and a maximum velocity (Vmax) of 9.76 +/- 0.78 nmol
      min-1 mg of protein-1. Enhanced rates of uptake were induced by growth on 2-CBa
      and 2-HBa, but not by growth on benzoate or 2,5-di-CBa. Intracellular
      accumulations of 2-CBa and 2-HBa were 109- and 42-fold greater, respectively,
      than the extracellular concentrations of these substrates and were indicative of
      uptake mediated by a transporter rather than driven by substrate catabolism
      ("metabolic drag"). Results of competitor screening tests indicated that the
      substrate range of the transporter did not include other o-halobenzoates that
      serve as growth substrates for strain D1 and for which the metabolism was
      initiated by the same dioxygenase as 2-CBa and 2-HBa. This suggested that
      multiple mechanisms for substrate uptake were coupled to the same catabolic
      enzyme. The preponderance of evidence from tests with metabolic inhibitors and
      artificial electrochemical gradients suggested that 2-CBa uptake was driven by
      ATP hydrolysis. If so, the 2-CBa transporter would be the first of the ATP
      binding cassette type implicated in uptake of haloaromatic acids.

PMID- 14660392
TI  - Genetic diversity of Campylobacter jejuni isolates from farm animals and the farm
      environment.
AB  - The genetic diversity of Campylobacter jejuni isolates from farm animals and
      their environment was investigated by multilocus sequence typing (MLST). A total
      of 30 genotypes, defined by allelic profiles (assigned to sequence types [STs]),
      were found in 112 C. jejuni isolates originating in poultry, cattle, sheep,
      starlings, and slurry. All but two of these genotypes belonged to one of nine C.
      jejuni clonal complexes previously identified in isolates from human disease and
      retail food samples and one clonal complex previously associated with an
      environmental source. There was some evidence for the association of certain
      clonal complexes with particular farm animals: isolates belonging to the ST-45
      complex predominated among poultry isolates but were absent among sheep isolates,
      while isolates belonging to the ST-61 and ST-42 complexes were predominant among
      sheep isolates but were absent from the poultry isolates. In contrast, ST-21
      complex isolates were distributed among the different isolation sources.
      Comparison with MLST data from 91 human disease isolates showed small but
      significant genetic differentiation between the farm and human isolates; however,
      representatives of six clonal complexes were found in both samples. These data
      demonstrate that MLST and the clonal complex model can be used to identify and
      compare the genotypes of C. jejuni isolates from farm animals and the environment
      with those from retail food and human disease.

PMID- 14660393
TI  - Predominance of vanA genotype among vancomycin-resistant Enterococcus isolates
      from poultry and swine in Costa Rica.
AB  - The use of avoparcin as a growth promoter is considered to have selected for
      vancomycin-resistant enterococci (VRE). In Costa Rica, the use of avoparcin for
      poultry and swine was intensive until the product was withdrawn from the market
      in 2000. We evaluated the presence of VRE in poultry, swine, and cattle fecal
      samples obtained during 1998 and 1999. A total of 185 VRE isolates were recovered
      from 116 out of 893 samples. Enterococcus faecium was the most frequently
      isolated species (50.8%), being predominant among poultry (71.6%) and swine
      (37.7%) isolates, but it was not recovered from the bovine samples. The second
      most-frequently-isolated species from poultry and swine, respectively, were E.
      durans (23.2%) and E. faecalis (21.7%). E. casseliflavus was the only species
      obtained from bovine samples, but it was not found among the avian isolates. An
      evident predominance of the vanA determinant among vancomycin-resistant
      enterococcal species from poultry and swine, but not from cattle, was observed
      and was similar to the situation in European countries before avoparcin was
      forbidden. The diversity of the vanA determinant in the isolates was assessed by
      detection of the IS1251 insertion in the vanSH intergenic region and of the
      IS1476 insertion in the vanXY intergenic region. However, in none of the 154
      vanA+ isolates recovered in this study were those insertions detected.

PMID- 14660394
TI  - Spatial analysis of archaeal community structure in grassland soil.
AB  - The complex structure of soil and the heterogeneity of resources available to
      microorganisms have implications for sampling regimens when the structure and
      diversity of microbial communities are analyzed. To assess the heterogeneity in
      community structure, archaeal communities, which typically contain sequences
      belonging to the nonthermophilic Crenarchaeota, were examined at two contrasting
      spatial scales by using PCR-denaturing gradient gel electrophoresis (DGGE)
      analysis followed by unweighted pair group method with arithmetic mean analysis
      of 16S rRNA- and ribosomal DNA-derived profiles. A macroscale analysis was
      carried out with soil cores taken at 2-m intervals along triplicate 8-m transects
      from both managed (improved) and natural (unimproved) grassland rhizosphere
      soils. A microscale analysis was carried out with a single soil core by assessing
      the effects of both sample size (10, 1, and 0.1 g) and distance between samples.
      The much reduced complexity of archaeal profiles compared to the complexity
      typical of the bacterial community facilitated visual comparison of profiles
      based on band presence and revealed different levels of heterogeneity between
      sets of samples. At the macroscale level, heterogeneity over the transect could
      not be related to grassland type. Substantial heterogeneity was observed across
      both improved and unimproved transects, except for one improved transect that
      exhibited substantial homogeneity, so that profiles for a single core were
      largely representative of the entire transect. At the smaller scale, the
      heterogeneity of the archaeal community structure varied with sample size within
      a single 8- by 8-cm core. The archaeal DGGE profiles for replicate 10-g soil
      samples were similar, while those for 1-g samples and 0.1-g samples showed
      greater heterogeneity. In addition, there was no relationship between the
      archaeal profiles and the distance between 1- or 0.1-g samples, although
      relationships between community structure and distance of separation may occur at
      a smaller scale. Our findings demonstrate the care required when workers attempt
      to obtain a representative picture of microbial community structure in the soil
      environment.

PMID- 14660395
TI  - Real-time PCR assay for detection and enumeration of Dekkera bruxellensis in
      wine.
AB  - Traditional methods to detect the spoilage yeast Dekkera bruxellensis from wine
      involve lengthy enrichments. To overcome this difficulty, we developed a
      quantitative real-time PCR method to directly detect and enumerate D.
      bruxellensis in wine. Specific PCR primers to D. bruxellensis were designed to
      the 26S rRNA gene, and nontarget yeast and bacteria common to the winery
      environment were not amplified. The assay was linear over a range of cell
      concentrations (6 log units) and could detect as little as 1 cell per ml in wine.
      The addition of large amounts of nontarget yeasts did not impact the efficiency
      of the assay. This method will be helpful to identify possible routes of D.
      bruxellensis infection in winery environments. Moreover, the time involved in
      performing the assay (3 h) should enable winemakers to more quickly make wine
      processing decisions in order to reduce the threat of spoilage by D.
      bruxellensis.

PMID- 14660396
TI  - Characterization of Vibrio fluvialis-like strains implicated in limp lobster
      disease.
AB  - Studies were undertaken to characterize and determine the pathogenic mechanisms
      involved in a newly described systemic disease in Homarus americanus (American
      lobster) caused by a Vibrio fluvialis-like microorganism. Nineteen isolates were
      obtained from eight of nine lobsters sampled. Biochemically, the isolates
      resembled V. fluvialis, and the isolates grew optimally at 20 degrees C; none
      could grow at temperatures above 23 degrees C. The type strain (1AMA) displayed a
      thermal reduction time (D value) of 5.77 min at 37 degrees C. All of the isolates
      required at least 1% NaCl for growth. Collectively, the data suggest that these
      isolates may embody a new biotype. Pulsed-field gel electrophoresis (PFGE)
      analysis of the isolates revealed five closely related subgroups. Some isolates
      produced a sheep hemagglutinin that was neither an outer membrane protein nor a
      metalloprotease. Several isolates possessed capsules. The isolates were highly
      susceptible to a variety of antibiotics tested. However, six isolates were
      resistant to erythromycin. Seventeen isolates harbored plasmids. Lobster
      challenge studies revealed that the 50% lethal dose of a plasmid-positive strain
      was 100-fold lower than that of a plasmid-negative strain, suggesting that the
      plasmid may enhance the pathogenicity of these microorganisms in lobsters.
      Microorganisms that were recovered from experimentally infected lobsters
      exhibited biochemical and PFGE profiles that were indistinguishable from those of
      the challenge strain. Tissue affinity studies demonstrated that the challenge
      microorganisms accumulated in heart and midgut tissues as well as in the
      hemolymph. Culture supernatants and polymyxin B lysates of the strains caused
      elongation of CHO cells in tissue culture, suggesting the presence of a hitherto
      unknown enterotoxin. Both plasmid-positive and plasmid-negative strains caused
      significant dose-related intestinal fluid accumulations in suckling mice. Absence
      of viable organisms in the intestinal contents of mice suggests that these
      microorganisms cause diarrhea in mice by intoxication rather than by an
      infectious process. Further, these results support the thermal reduction data at
      37 degrees C and suggest that the mechanism(s) that led to fluid accumulation in
      mice differs from the disease process observed in lobsters by requiring neither
      the persistence of viable microorganisms nor the presence of plasmids. In
      summary, results of lobster studies satisfy Koch's postulates at the organismal
      and molecular levels; the findings support the hypothesis that these V. fluvialis
      like organisms were responsible for the originally described systemic disease,
      which is now called limp lobster disease.

PMID- 14660397
TI  - Biological traits of Xylella fastidiosa strains from grapes and almonds.
AB  - Xylella fastidiosa is a xylem-limited bacterium that causes various diseases,
      among them Pierce's disease of grapevine (PD) and almond leaf scorch (ALS). PD
      and ALS have long been considered to be caused by the same strain of this
      pathogen, but recent genetic studies have revealed differences among X.
      fastidiosa isolated from these host plants. We tested the hypothesis that ALS is
      caused by PD and ALS strains in the field and found that both groups of X.
      fastidiosa caused ALS and overwintered within almonds after mechanical
      inoculation. Under greenhouse conditions, all isolates caused ALS and all
      isolates from grapes caused PD. However, isolates belonging to almond genetic
      groupings did not cause PD in inoculated grapes but systemically infected grapes
      with lower frequency and populations than those belonging to grape strains.
      Isolates able to cause both PD and ALS developed 10-fold-higher concentrations of
      X. fastidiosa in grapes than in almonds. In the laboratory, isolates from grapes
      overwintered with higher efficiency in grapes than in almonds and isolates from
      almonds overwintered better in almonds than in grapes. We assigned strains from
      almonds into groups I and II on the basis of their genetic characteristics,
      growth on PD3 solid medium, and bacterial populations within inoculated
      grapevines. Our results show that genetically distinct strains from grapes and
      almonds differ in population behavior and pathogenicity in grapes and in the
      ability to grow on two different media.

PMID- 14660398
TI  - Identification and population dynamics of yeasts in sourdough fermentation
      processes by PCR-denaturing gradient gel electrophoresis.
AB  - Four sourdoughs (A to D) were produced under practical conditions, using a
      starter obtained from a mixture of three commercially available sourdough
      starters and baker's yeast. The doughs were continuously propagated until the
      composition of the microbiota remained stable. A fungi-specific PCR-denaturing
      gradient gel electrophoresis (DGGE) system was established to monitor the
      development of the yeast biota. The analysis of the starter mixture revealed the
      presence of Candida humilis, Debaryomyces hansenii, Saccharomyces cerevisiae, and
      Saccharomyces uvarum. In sourdough A (traditional process with rye flour), C.
      humilis dominated under the prevailing fermentation conditions. In rye flour
      sourdoughs B and C, fermented at 30 and 40 degrees C, respectively, S. cerevisiae
      became predominant in sourdough B, whereas in sourdough C the yeast counts
      decreased within a few propagation steps below the detection limit. In sourdough
      D, which corresponded to sourdough C in temperature but was produced with rye
      bran, Candida krusei became dominant. Isolates identified as C. humilis and S.
      cerevisiae were shown by randomly amplified polymorphic DNA-PCR analysis to
      originate from the commercial starters and the baker's yeast, respectively. The
      yeast species isolated from the sourdoughs were also detected by PCR-DGGE.
      However, in the gel, additional bands were visible. Because sequencing of these
      PCR fragments from the gel failed, cloning experiments with 28S rRNA amplicons
      obtained from rye flour were performed, which revealed Cladosporium sp.,
      Saccharomyces servazii, S. uvarum, an unculturable ascomycete, Dekkera
      bruxellensis, Epicoccum nigrum, and S. cerevisiae. The last four species were
      also detected in sourdoughs A, B, and C.

PMID- 14660399
TI  - Survival of Helicobacter pylori in a natural freshwater environment.
AB  - The mode by which Helicobacter pylori, the causative agent of most gastric
      ulcers, is transmitted remains undetermined. Epidemiological evidence suggests
      these organisms are waterborne; however, H. pylori has rarely been grown from
      potential water sources. This may be due to the ability of this organism to
      rapidly enter the viable but nonculturable (VBNC) state. Our investigation
      examines the entrance of H. pylori into this state in laboratory cultures and a
      natural freshwater environment as well as the relationship between morphology and
      culturability. To this end, membrane diffusion chambers were utilized to expose
      the cells to the natural fluctuations of a freshwater stream. In both the
      laboratory and environment, samples were assayed for culturability using plate
      counts and stained using a LIVE/DEAD BacLight assay for viability and
      morphological determinations. Additionally, water samples were collected, six
      environmental parameters were measured, and resuscitation conditions were
      examined. H. pylori was observed to lose culturability in the laboratory and
      stream, although viability was maintained. While the results of our study agree
      with those of previous studies which suggested that there is a transition in
      morphology from rods to cocci as culturability is lost, the morphological
      distribution of cells did not change as culturability was lost in the
      environment. The majority of cells in the VBNC state in the laboratory are cocci;
      however, all morphological forms were present in the environment. The results of
      these studies suggest that H. pylori persists in laboratory cultures and the
      environment in the VBNC state and that cells in this state represent a public
      health hazard.

PMID- 14660400
TI  - Enumeration and characterization of iron(III)-reducing microbial communities from
      acidic subsurface sediments contaminated with uranium(VI).
AB  - Iron(III)-reducing bacteria have been demonstrated to rapidly catalyze the
      reduction and immobilization of uranium(VI) from contaminated subsurface
      sediments. Thus, these organisms may aid in the development of bioremediation
      strategies for uranium contamination, which is prevalent in acidic subsurface
      sediments at U.S. government facilities. Iron(III)-reducing enrichment cultures
      were initiated from pristine and contaminated (high in uranium, nitrate; low pH)
      subsurface sediments at pH 7 and pH 4 to 5. Enumeration of Fe(III)-reducing
      bacteria yielded cell counts of up to 240 cells ml(-1) for the contaminated and
      background sediments at both pHs with a range of different carbon sources
      (glycerol, acetate, lactate, and glucose). In enrichments where nitrate
      contamination was removed from the sediment by washing, MPN counts of Fe(III)
      reducing bacteria increased substantially. Sediments of lower pH typically
      yielded lower counts of Fe(III)-reducing bacteria in lactate- and acetate-amended
      enrichments, but higher counts were observed when glucose was used as an electron
      donor in acidic enrichments. Phylogenetic analysis of 16S rRNA gene sequences
      extracted from the highest positive MPN dilutions revealed that the predominant
      members of Fe(III)-reducing consortia from background sediments were closely
      related to members of the Geobacteraceae family, whereas a recently characterized
      Fe(III) reducer (Anaeromyxobacter sp.) and organisms not previously shown to
      reduce Fe(III) (Paenibacillus and Brevibacillus spp.) predominated in the Fe(III)
      reducing consortia of contaminated sediments. Analysis of enrichment cultures by
      terminal restriction fragment length polymorphism (T-RFLP) strongly supported the
      cloning and sequencing results. Dominant members of the Fe(III)-reducing
      consortia were observed to be stable over several enrichment culture transfers by
      T-RFLP in conjunction with measurements of Fe(III) reduction activity and carbon
      substrate utilization. Enrichment cultures from contaminated sites were also
      shown to rapidly reduce millimolar amounts of U(VI) in comparison to killed
      controls. With DNA extracted directly from subsurface sediments, quantitative
      analysis of 16S rRNA gene sequences with MPN-PCR indicated that Geobacteraceae
      sequences were more abundant in pristine compared to contaminated
      environments,whereas Anaeromyxobacter sequences were more abundant in
      contaminated sediments. Thus, results from a combination of cultivation-based and
      cultivation-independent approaches indicate that the abundance/community
      composition of Fe(III)-reducing consortia in subsurface sediments is dependent
      upon geochemical parameters (pH, nitrate concentration) and that microorganisms
      capable of producing spores (gram positive) or spore-like bodies
      (Anaeromyxobacter) were representative of acidic subsurface environments.

PMID- 14660401
TI  - Single-copy green fluorescent protein gene fusions allow accurate measurement of
      Salmonella gene expression in vitro and during infection of mammalian cells.
AB  - We developed a reliable and flexible green fluorescent protein (GFP)-based system
      for measuring gene expression in individual bacterial cells. Until now, most
      systems have relied upon plasmid-borne gfp gene fusions, risking problems
      associated with plasmid instability. We show that a recently developed GFP
      variant, GFP+, is suitable for assessing bacterial gene expression. Various gfp+
      transcriptional fusions were constructed and integrated as single copies into the
      chromosome of Salmonella enterica serovar Typhimurium. A comparison of the
      expression levels of proU-lacZ and proU-gfp+ fusions showed that GFP+ reported
      proU activity in individual Salmonella cells as accurately as beta-galactosidase
      reported activity for entire populations. The single-copy gfp+ fusions were ideal
      for monitoring up- and downregulation of Salmonella virulence genes. We
      discovered that in vitro induction of the SPI1gene prgH occurs only in a portion
      of the population and that the proportion varies with the growth phase. We
      determined the level of expression of the SPI2 gene ssaG in bacteria released
      from murine macrophages. Our results demonstrate for the first time that single
      copy GFP+ fusions reliably report gene expression in simple and complex
      environments. This approach promises to allow accurate measurement of gene
      expression in individual bacteria during animal infection.

PMID- 14660402
TI  - Role of the glycine betaine and carnitine transporters in adaptation of Listeria
      monocytogenes to chill stress in defined medium.
AB  - The food-borne pathogen Listeria monocytogenes proliferates at refrigeration
      temperatures, rendering refrigeration ineffective in the preservation of Listeria
      contaminated foods. The uptake and intracellular accumulation of the potent
      compatible solutes glycine betaine and carnitine has been shown to be a key
      mediator of the pathogen's cold-tolerant phenotype. To date, three compatible
      solute systems are known to operate in L. monocytogenes: glycine betaine porter I
      (BetL), glycine betaine porter II (Gbu), and the carnitine transporter OpuC. We
      investigated the specificity of each transporter towards each compatible solute
      at 4 degrees C by examining mutant derivatives of L. monocytogenes 10403S that
      possess each of the transporters in isolation. Kinetic and steady-state
      compatible solute accumulation data together with growth rate experiments
      demonstrated that under cold stress glycine betaine transport is primarily
      mediated by Gbu and that Gbu-mediated betaine uptake results in significant
      growth stimulation of chill-stressed cells. BetL and OpuC can serve as minor
      porters for the uptake of betaine, and their action is capable of providing a
      small degree of cryotolerance. Under cold stress, carnitine transport occurs
      primarily through OpuC and results in a high level of cryoprotection. Weak
      carnitine transport occurs via Gbu and BetL, conferring correspondingly weak
      cryoprotection. No other transporter in L. monocytogenes 10403S appears to be
      involved in transport of either compatible solute at 4 degrees C, since a triple
      mutant strain yielded neither transport nor accumulation of glycine betaine or
      carnitine and could not be rescued by either osmolyte when grown at that
      temperature.

PMID- 14660403
TI  - Experimental examination of bacteriophage latent-period evolution as a response
      to bacterial availability.
AB  - For obligately lytic bacteriophage (phage) a trade-off exists between fecundity
      (burst size) and latent period (a component of generation time). This trade-off
      occurs because release of phage progeny from infected bacteria coincides with
      destruction of the machinery necessary to produce more phage progeny. Here we
      employ phage mutants to explore issues of phage latent-period evolution as a
      function of the density of phage-susceptible bacteria. Theory suggests that
      higher bacterial densities should select for shorter phage latent periods.
      Consistently, we have found that higher host densities (>/== approximately 10(7)
      bacteria/ml) can enrich stocks of phage RB69 for variants that display shorter
      latent periods than the wild type. One such variant, dubbed sta5, displays a
      latent period that is approximately 70 to 80% of that of the wild type-which is
      nearly as short as the RB69 eclipse period-and which has a corresponding burst
      size that is approximately 30% of that of the wild type. We show that at higher
      host densities (>/== approximately 10(7) bacteria/ml) the sta5 phage can
      outcompete the RB69 wild type, though only under conditions of direct (same
      culture) competition. We interpret this advantage as corresponding to slightly
      faster sta5 population growth, resulting in multifold increases in mutant
      frequency during same-culture growth. The sta5 advantage is lost, however, given
      indirect (different-culture) competition between the wild type and mutant or
      given same-culture competition but at lower densities of phage-susceptible
      bacteria (</= approximately 10(6) bacteria/ml). From these observations we
      suggest that phage displaying very short latent periods may be viewed as
      specialists for propagation when bacteria within cultures are highly prevalent
      and transmission between cultures is easily accomplished.

PMID- 14660404
TI  - GTP cyclohydrolase I: purification, characterization, and effects of inhibition
      on nitric oxide synthase in nocardia species.
AB  - GTP cyclohydrolase I (GTPCH) catalyzes the first step in pteridine biosynthesis
      in Nocardia sp. strain NRRL 5646. This enzyme is important in the biosynthesis of
      tetrahydrobiopterin (BH4), a reducing cofactor required for nitric oxide synthase
      (NOS) and other enzyme systems in this organism. GTPCH was purified more than
      5,000-fold to apparent homogeneity by a combination of ammonium sulfate
      fractionation, GTP-agarose, DEAE Sepharose, and Ultragel AcA 34 chromatography.
      The purified enzyme gave a single band for a protein estimated to be 32 kDa by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular mass of
      the native enzyme was estimated to be 253 kDa by gel filtration, indicating that
      the active enzyme is a homo-octamer. The enzyme follows Michaelis-Menten
      kinetics, with a Km for GTP of 6.5 micromoles. Nocardia GTPCH possessed a unique
      N-terminal amino acid sequence. The pH and temperature optima for the enzyme were
      7.8 and 56 degrees C, respectively. The enzyme was heat stable and slightly
      activated by potassium ion but was inhibited by calcium, copper, zinc, and
      mercury, but not magnesium. BH4 inhibited enzyme activity by 25% at a
      concentration of 100 micromoles. 2,4-Diamino-6-hydroxypyrimidine (DAHP) appeared
      to competitively inhibit the enzyme, with a Ki of 0.23 mM. With Nocardia
      cultures, DAHP decreased medium levels of NO2- plus NO3-. Results suggest that in
      Nocardia cells, NOS synthesis of nitric oxide is indirectly decreased by reducing
      the biosynthesis of an essential reducing cofactor, BH4.

PMID- 14660405
TI  - Effect of food processing-related stresses on acid tolerance of Listeria
      monocytogenes.
AB  - Stationary-phase cells of Listeria monocytogenes grown in glucose-free or glucose
      containing media were exposed for 90 min to various stresses, including acid
      stress (pH 4.0 to 7.0), osmotic stress (10.5 to 20.5% NaCl), and various
      temperatures (-5 to 50 degrees C), and were further exposed to pH 3.5. Exposure
      to a mildly acidic (pH 5.0 to 6.0) environment provided protection of the
      pathogen against acid upon subsequent exposure. This adaptive response, however,
      was found to be strongly dependent on other environmental conditions during the
      shock, such as temperature or the simultaneous presence of a second stress factor
      (NaCl). Growth of L. monocytogenes in the presence of glucose resulted in
      enhanced survival of the pathogen at pH 3.5. Sublethal stresses other than acidic
      stresses, i.e., osmotic, heat, and low-temperature stresses, did not affect the
      acid resistance of L. monocytogenes (P > 0.5). More-severe levels of these
      stresses, however, resulted in sensitization of the pathogen to acid.

PMID- 14660406
TI  - Comparative sequence analysis of the tuf and recA genes and restriction fragment
      length polymorphism of the internal transcribed spacer region sequences supply
      additional tools for discriminating Bifidobacterium lactis from Bifidobacterium
      animalis.
AB  - The relationship between Bifidobacterium lactis and Bifidobacterium animalis was
      examined by comparative analysis of tuf and recA gene sequences and by
      restriction fragment length polymorphism analysis of their internal 16S-23S
      transcribed spacer region sequences. The bifidobacterial strains investigated
      could be divided into two distinct groups within a single species based on the
      tuf, recA, and 16S-23S spacer region sequence analysis. Therefore, all strains of
      B. lactis and B. animalis could be unified as the species B. animalis and divided
      into two subspecies, Bifidobacterium animalis subsp. lactis and Bifidobacterium
      animalis subsp. animalis.

PMID- 14660407
TI  - Avian reservoirs and zoonotic potential of the emerging human pathogen
      Helicobacter canadensis.
AB  - A polyphasic identification approach was used to investigate the taxonomic
      position of Campylobacter-like isolates recovered from barnacle geese (Branta
      leucopsis) and Canada geese (Branta candensis). Seven strains were selected from
      a collection of 21 isolates and analyzed by extensive phenotypic testing; four
      strains were characterized by 16S rRNA gene sequence analysis. The results
      clearly identified the bird isolates as Helicobacter canadensis, recently
      described as an emerging human pathogen. This is the first report of an animal
      reservoir for this organism and of its presence in Europe and confirms the
      zoonotic potential of H. canadensis.

PMID- 14660408
TI  - Chemoattraction of Vibrio fischeri to serine, nucleosides, and N-acetylneuraminic
      acid, a component of squid light-organ mucus.
AB  - Newly hatched juveniles of the Hawaiian squid Euprymna scolopes rapidly become
      colonized by the bioluminescent marine bacterium Vibrio fischeri. Motility is
      required to establish the symbiotic colonization, but the role of chemotaxis is
      unknown. In this study we analyzed chemotaxis of V. fischeri to a number of
      potential attractants. The bacterium migrated toward serine and most sugars
      tested. V. fischeri also exhibited the unusual ability to migrate to nucleosides
      and nucleotides as well as to N-acetylneuraminic acid, a component of squid
      mucus.

PMID- 14660409
TI  - Detection of a Salmonella enterica serovar California strain spreading in spanish
      feed mills and genetic characterization with DNA microarrays.
AB  - We performed an epidemiological study on Salmonella isolated from raw plant-based
      feed in Spanish mills. Overall, 32 different Salmonella serovars were detected.
      Despite its rare occurrence in humans and animals, Salmonella enterica serovar
      California was found to be the predominant serovar in Spanish feed mills.
      Different typing techniques showed that isolates of this serovar were genetically
      closely related, and comparative genomic hybridization using microarray
      technology revealed 23 S. enterica serovar Typhimurium LT2 gene clusters that are
      absent from serovar California.

PMID- 14660410
TI  - Application of genome-wide expression analysis to identify molecular markers
      useful in monitoring industrial fermentations.
AB  - Genome-wide expression analysis of an industrial strain of Saccharomyces
      cerevisiae identified the YOR387c and YGL258w homologues as highly inducible in
      zinc-depleted conditions. Induction was specific for zinc deficiency and was
      dependent on Zap1p. The results indicate that these sequences may be valuable
      molecular markers for detecting zinc deficiency in industrial fermentations.

PMID- 14660411
TI  - Prevalence of cholera toxin genes (ctxA and zot) among non-O1/O139 Vibrio
      cholerae strains from Newport Bay, California.
AB  - The examination of 137 non-O1/O139 Vibrio cholerae isolates from Newport Bay,
      California, indicated the presence of diverse genotypes and a temporal
      succession. Unexpectedly, the cholera toxin gene (ctxA) was found in 17% of the
      strains, of which one-third were also positive for the zot gene. This suggests
      that ctxA is prevalent in the region of nonepidemicity and is likely to have an
      environmental origin.

PMID- 14660412
TI  - Case study of the distribution of mucosa-associated Bifidobacterium species,
      Lactobacillus species, and other lactic acid bacteria in the human colon.
AB  - The distribution of mucosa-associated bacteria, bifidobacteria and lactobacilli
      and closely related lactic acid bacteria, in biopsy samples from the ascending,
      transverse, and descending parts of the colon from four individuals was
      investigated by denaturing gradient gel electrophoresis (DGGE). Bifidobacterial
      genus-specific, Lactobacillus group-specific, and universal bacterial primers
      were used in a nested PCR approach to amplify a fragment of the 16S rRNA gene.
      DGGE profiles of the bifidobacterial community were relatively simple, with one
      or two amplicons detected at most sampling sites in the colon. DGGE profiles
      obtained with Lactobacillus group-specific primers were complex and varied with
      host and sampling site in the colon. The overall bacterial community varied with
      host but not sampling site.

PMID- 14660413
TI  - A newly discovered verotoxin variant, VT2g, produced by bovine verocytotoxigenic
      Escherichia coli.
AB  - A new verotoxin (VT) variant, designated vt2g, was identified from a bovine
      strain of verocytotoxigenic Escherichia coli (VTEC) serotype O2:H25. When vt2g
      was aligned with published sequences of vt2 and vt variants, it exhibited the
      highest DNA sequence homology with vt2 and vt2c. However, vt2g was not detected
      by vt2-specific primers and probes, although it was partially neutralized by an
      antiserum to the VT2A subunit. VT2g was cytotoxic for Vero and HeLa cells and was
      not activated by mouse intestinal mucus. The vt2g gene was detected in 3 of 409
      (0.7%) bovine VTEC strains, including serotypes O2:H25, O2:H45 and Ont:H-.

PMID- 14660414
TI  - Antifungal 3-hydroxy fatty acids from Lactobacillus plantarum MiLAB 14.
AB  - We report the identification and chemical characterization of four antifungal
      substances, 3-(R)-hydroxydecanoic acid, 3-hydroxy-5-cis-dodecenoic acid, 3-(R)
      hydroxydodecanoic acid and 3-(R)-hydroxytetradecanoic acid, from Lactobacillus
      plantarum MiLAB 14. The concentrations of the 3-hydroxy fatty acids in the
      supernatant followed the bacterial growth. Racemic mixtures of the saturated 3
      hydroxy fatty acids showed antifungal activity against different molds and yeasts
      with MICs between 10 and 100 micrograms ml-1.

PMID- 14660415
TI  - Construction of a genetically modified wine yeast strain expressing the
      Aspergillus aculeatus rhaA gene, encoding an alpha-L-rhamnosidase of enological
      interest.
AB  - The Aspergillus aculeatus rhaA gene encoding an alpha-L-rhamnosidase has been
      expressed in both laboratory and industrial wine yeast strains. Wines produced in
      microvinifications, conducted using a combination of the genetically modified
      industrial strain expressing rhaA and another strain expressing a beta
      glucosidase, show increased content mainly of the aromatic compound linalool.

PMID- 14660416
TI  - Genetic characterization of the carotenoid biosynthetic pathway in
      Methylobacterium extorquens AM1 and isolation of a colorless mutant.
AB  - Genomic searches were used to reconstruct the putative carotenoid biosynthesis
      pathway in the pink-pigmented facultative methylotroph Methylobacterium
      extorquens AM1. Four genes for putative phytoene desaturases were identified. A
      colorless mutant was obtained by transposon mutagenesis, and the insertion was
      shown to be in one of the putative phytoene desaturase genes. Mutations in the
      other three did not affect color. The tetracycline marker was removed from the
      original transposon mutant, resulting in a pigment-free strain with wild-type
      growth properties useful as a tool for future experiments.

PMID- 14660417
TI  - The most serious challenge facing academic medicine's institutions.

PMID- 14660418
TI  - Role modeling in physicians' professional formation: reconsidering an essential
      but untapped educational strategy.
AB  - Forming technically proficient, professional, and humanistic physicians for the
      21st century is no easy task. Mountains of biomedical knowledge must be acquired,
      diagnostic competence achieved, effective communication skills developed, and a
      solid and applicable understanding of the practice and role of physicians in
      society today must be reached. The central experience for learners in this
      complex and challenging terrain is the "modeling of" and "learning how to be" a
      caregiver and health professional. Role modeling remains one crucial area where
      standards are elusive and where repeated negative learning experiences may
      adversely impact the development of professionalism in medical students and
      residents. The literature is mainly descriptive, defining the attributes of good
      role models from both learners and practitioners' perspectives. Because
      physicians are not "playing a role" as an actor might, but "embodying" different
      types of roles, the cognitive and behavioral processes associated with
      successfully internalizing roles (e.g., the good doctor/medical educator) are
      important. In this article, the authors identify foundational questions regarding
      role models and professional character formation; describe major social and
      historical reasons for inattention to character formation in new physicians; draw
      insights about this important area from ethics and education theory
      (philosophical inquiry, apprenticeship, situated learning, observational
      learning, reflective practice); and suggest the practical consequences of this
      work for faculty recruitment, affirmation, and development.

PMID- 14660419
TI  - Student providers aspiring to rural and underserved experiences at the University
      of Washington: promoting team practice among the health care professions.
AB  - In the United States there are shortages of health care providers for both rural
      and underserved populations. There are also shortages of interprofessional or
      team-based training programs. To address these problems, the University of
      Washington's Area Health Education Center program and School of Medicine offer a
      voluntary extracurricular program for students in the university's six health
      science schools. The Student Providers Aspiring to Rural and Underserved
      Experiences (SPARX) program is an interprofessional, student-operated,
      center/school-supported program consisting of a wide range of activities. SPARX
      supports students interested in practicing among rural and urban medically
      underserved patients and in interacting with their peers in other health
      professions schools. A brief history and description of the program are
      presented, along with results of a survey of students indicating that SPARX
      reinforces their interest in practice among the underserved and influences their
      understanding of other health professions. Data on residency choices of medical
      students who have participated in the SPARX program are presented, indicating
      that these students are more likely to select primary care residency programs
      than the average students in their classes.

PMID- 14660420
TI  - Responding to the ACGME's competency requirements: an innovative instrument from
      the University of Virginia's neurology residency.
AB  - The general competencies mandated by the Accreditation Council for Graduate
      Medical Education (ACGME) Outcome Project have resulted in new training
      requirements for most residency programs. To determine the training program
      changes necessary because of these new standards, the neurology residency program
      at the University of Virginia developed a simple grid-like instrument that links
      the objectives for residents' major rotations with the six ACGME general
      competencies. This instrument, created in 2002, helped the program develop
      specific training elements related to the general competencies that were
      identified as missing from the residency. The instrument was then converted to an
      evaluation tool that allows attending physicians to assess individual residents'
      competencies for each objective in all major rotations. The author describes the
      assessment and evaluation instruments, called Self Assessment and Vital
      Evaluation (SAVE), and their usefulness in the University of Virginia neurology
      residency program's initial response to the new standards. She also suggests that
      these instruments, with some modifications, may be of value to other residency
      programs.

PMID- 14660421
TI  - Developing culturally competent community faculty: a model program.
AB  - The Liaison Committee on Medical Education recently set standards for cultural
      diversity training as part of the medical school curriculum. To the authors'
      knowledge, this is the first description of a faculty-development program
      designed to develop the capacity of the clinical faculty to integrate culture and
      advocacy education into clinical training. The paper describes the first two
      years of the development of an ongoing cultural competence curriculum that has
      been integrated into the training of community preceptors from 13 medical schools
      in New England and New York. The training, entitled"Teaching the Culture of the
      Community," consists of four 2.5-hour modules that include interactive lectures
      and small-group role-play exercises on cultural needs assessment, patient
      centered interviewing, feedback on cultural issues and use of the community to
      enhance cultural understanding. The 137 participants in the first two years of
      the program (1999-00 and 2000-01) reported a high level of acceptance of the
      curriculum. In the second year, the program began to document participants' self
      reported"intention to change" in relation to the cultural competence curriculum.
      Many participants reported plans to change aspects of their clinical care and
      their teaching practices. Intentions to change were most frequently expressed in
      the context of content on effective communication skills. In summary, cultural
      competency training has been successfully integrated into an existing faculty
      development program for community-based preceptors.

PMID- 14660422
TI  - A workshop for medical students on deafness and hearing impairments.
AB  - There is a current need to improve health care delivery to deaf and hearing
      impaired persons. The author designed an educational workshop for medical
      students and others as an initial step to address this need. The workshop was
      offered electively during 1997 and 1998 to first-year and second-year medical
      students at Dalhousie University, Nova Scotia, Canada. The workshop involved a
      broad, multidisciplinary scope, may have been the first of its kind in Canada,
      and is still one of the few documented ways to approach medical education about
      deafness and hearing impairments. Attendees explored general information on
      hearing impairments, communication between the hearing-impaired patient and his
      or her physician, and multicultural, technological, and ethical aspects of caring
      for hearing-impaired patients. There was an initial questionnaire, group
      exercises, lectures, student interviews of volunteer deaf "patients,"
      discussions, and a "hands-on" materials display. The workshop was a low-cost and
      easily reproducible method of educating medical students about hearing
      impairments. If found to be educationally effective through future research, this
      type of workshop may foster better care to deaf and hearing-impaired persons by
      inclusion into medical school and continuing education curricula.

PMID- 14660423
TI  - Teaching students how to read and write science: a mandatory course on scientific
      research and communication in medicine.
AB  - The authors describe the development and introduction of a course on scientific
      methodology and communication into the medical curriculum in a country outside of
      the mainstream scientific world. As editors of a general medical journal in
      Croatia, they learned that their colleagues had important and interesting data
      but no skills for presenting them in a scientific article. To alleviate the lack
      of education in research methodology and writing, the authors developed and
      introduced a mandatory course in scientific methodology and communication into
      the medical curriculum of the largest Croatian medical school. The course is
      structured into lectures, medium-sized-group discussions, and problem-solving
      small-group work, and is focused on (1) principles of scientific research; (2)
      access to medical literature and bibliographic databases; (3) study design and
      analysis and presentation of data; (4) assessing and writing a scientific
      article; and (5) responsible conduct of research. The course has been running
      since 1995-96 and is already showing results, visible in the more positive
      attitude of students toward scientific research and evidence-based medicine, and
      a significant number of students working on research projects and publishing
      scientific papers. The authors and colleagues also run continuing education
      courses for young academic physicians and an annual advanced workshop on
      scientific writing, involving academic physicians from all of southeastern
      Europe. The long-term goal is to create a critical mass of academic physicians
      with critical appraisal skills needed for evidence-based medicine and with skills
      for effectively communicating their research to the international scientific
      community.

PMID- 14660424
TI  - A standardized patient enrolled in medical school considers the national clinical
      skills examination.
AB  - The National Board of Medical Examiners' recent decision to include a clinical
      skills examination as part of the licensing requirements for U.S. medical
      graduates has generated widespread discussion about the role of standardized
      patients in medical education. The author demonstrates that while specific
      clinical skills can and should be integrated into the medical school curriculum,
      any assessment of these skills using interactions with standardized patients must
      allow for a fuller range of responses and immediate, multifaceted feedback
      (content, process, and patient satisfaction) than would be allowed in the
      proposed Step 2 Clinical Skills. The presence of a national examination would
      pressure medical schools to adopt the very limited model of patient-physician
      interaction favored by the National Board of Medical Examiners. In addition, the
      author argues that the cost of registering for the examination and traveling to
      one of the few test sites on borrowed money is not justified to verify skills
      that may be reliably assessed locally.

PMID- 14660425
TI  - How to be good.

PMID- 14660427
TI  - A humanistic role model in my medical career.

PMID- 14660428
TI  - Re-examining the value of medical grand rounds.
AB  - PURPOSE: To study medical grand rounds, the cornerstone of a department of
      medicine's educational programs. METHOD: Between April and June 2001, a
      questionnaire was sent to chairs of departments of medicine at the 389 U.S.
      hospitals with medicine residency programs accredited by the Accreditation
      Council for Graduate Medical Education. Data were collected on the objectives and
      attendance, educational structure, perceived quality, and costs of medical grand
      rounds. RESULTS: Three hundred questionnaires were returned (77%). Grand rounds
      were offered by 97% of departments and accredited for continuing medical
      education in 96% of hospitals. The most important objectives were to educate,
      showcase faculty role models, and promote a collegial atmosphere. Patients were
      present at grand rounds less than 3% of the time. Grand rounds were predominantly
      lecture based; only 10% were clinical case presentations or interactive
      workshops/small groups, the formats proven most effective for facilitating adult
      learning and a humanistic approach to patients. Curricular tenets of needs
      assessment, program evaluation, and knowledge assessment were performed in only
      73%, 59%, and 17% of programs, respectively. University hospitals were less
      likely to incorporate these principles (p <.01). Although respondents attested to
      the high quality of grand rounds, many potential attendees missed more than half
      the sessions. Grand rounds were the most expensive conference in 78% of
      departments, with the pharmaceutical industry providing the majority of the
      funding. CONCLUSIONS: Medical grand rounds are costly and often do not take into
      account learners' needs. Departments of medicine should reevaluate their
      commitment to grand rounds.

PMID- 14660429
TI  - Research during pediatric residency: predictors and resident-determined
      influences.
AB  - PURPOSE: Participation in research during residency is thought to be a strong
      predictor of future research activity; however, the proportion of residents who
      actually engage in research is small. This study examined (1) which factors are
      associated with research during residency; (2) which factors influence residents'
      abilities to conduct research; and (3) the number of residents conducting
      research in a research-oriented training program. METHOD: One hundred fifteen
      pediatrics residents were asked at a housestaff retreat to complete a
      questionnaire about their attitudes toward research. Comparisons between those
      who were or were not conducting research during residency were made using chi
      square or Fisher exact tests; stepwise logistic regression was used to identify
      factors associated with conducting research during residency. RESULTS: The
      response rate was 95% (n = 110, or 82% of the residency program). Respondents
      were representative of postgraduate year, gender, and residency track. Although
      92% of respondents reported having conducted research before residency, only 18%
      were currently involved in research (p <.001). Fifty-five percent reported
      interest in conducting research. Advanced degrees and future career plans
      influenced their decisions to do research (p <.05). Respondents were more likely
      to conduct clinical research than basic science or laboratory-based research (14%
      versus 3% of all respondents, p =.007). The most commonly identified influences
      to conducting research were availability of time (97%), personal interest in
      research (84%), availability of opportunities (76%), and mentors on hand (72%).
      CONCLUSION: Interest in research during residency is high, but participation in
      research is low. There are several influences to the types and amounts of
      research conducted during pediatrics residency.

PMID- 14660430
TI  - Effect of an undergraduate medical curriculum on students' self-directed
      learning.
AB  - PURPOSE: Lifelong, self-directed learning (SDL) has been identified as an
      important ability for medical graduates. To evaluate the effect of the University
      of Toronto Faculty of Medicine's revised undergraduate medical curriculum on
      students' SDL, a cross-sectional study was conducted. METHOD: A questionnaire
      package was mailed to 280 randomly selected students, 70 from each of the four
      years of the curriculum. The package contained the two most widely recognized,
      extensively used, and validated instruments of SDL (Guglielmino's 58-item Self
      Directed Learning Readiness Scale and Oddi's 24-item Continuous Learning
      Inventory) and Ryan's two-part Self-Assessment Questionnaire. An identification
      number and sociodemographic questions were included with the questionnaires. Data
      analysis was completed using chi-square for differences of proportions, analysis
      of variance for differences between means, and linear regression for trends.
      RESULTS: A total of 250 (89.3%) complete questionnaire packages were returned. No
      significant trend in SDL was evident by curriculum year, and similar SDL levels
      were observed for women and men. However, a significant positive trend in SDL was
      found with the highest level of premedical education achieved (undergraduate
      only, masters, or doctoral). Further, students' perceptions concerning the
      importance of SDL decreased according to year in the curriculum. CONCLUSION: This
      study found no evidence that students' self-reported SDL is positively influenced
      by the current undergraduate medical curriculum at the University of Toronto
      Faculty of Medicine.

PMID- 14660431
TI  - Evaluation of a community-based pediatrics residency rotation using narrative
      analysis.
AB  - PURPOSE: To evaluate the extent to which a community pediatrics rotation in
      disadvantaged neighborhoods provided residents with a self-assessed change in
      knowledge, attitudes, and skills useful for improving the health of children at
      the community level. METHOD: All pediatrics and medicine-pediatrics residents at
      the University of Rochester Medical Center participate in a two-week community
      based rotation. At the end of each rotation, residents were asked to write a
      short essay on what they learned during the experience. An interdisciplinary team
      conducted a retrospective, qualitative analysis of residents' essays looking for
      recurring themes. Essays were also examined for narrative plot elements that
      would indicate a causal sequence of events indicating some transformation of the
      learner. RESULTS: Of the 25 essays reviewed, each gave evidence of at least one
      of three themes: increased knowledge of lives in poverty, renewed enthusiasm for
      advocacy, and increased skill in making referrals. Although many residents
      expressed initial skepticism of the value of a community rotation, none noted any
      negative final impression. The narrative structure of residents' essays also
      showed evidence of some transformation of the learner. CONCLUSIONS: A community
      pediatrics rotation can be a successful educational experience for providing
      residents with knowledge of how pervasive poverty impacts children and families.
      Reported changes in attitudes and skills require further evaluation to
      demonstrate that they can be applied in practice.

PMID- 14660432
TI  - Effect of two Howard Hughes Medical Institute research training programs for
      medical students on the likelihood of pursuing research careers.
AB  - PURPOSE: To assess the effect of Howard Hughes Medical Institute's (HHMI) two one
      year research training programs for medical students on the awardees' research
      careers. METHOD: Awardees of the HHMI Cloister Program who graduated between 1987
      and 1995 and awardees of the HHMI Medical Fellows Program who graduated between
      1991 and 1995 were compared with unsuccessful applicants to the programs and MD
      PhD students who graduated during the same periods. Logistic regression analyses
      were conducted to assess research career outcomes while controlling for academic
      and demographic variables that could affect selection to the programs. RESULTS:
      Participation in both HHMI programs increased the likelihood of receiving
      National Institutes of Health postdoctoral support. Participation in the Cloister
      Program also increased the likelihood of receiving a faculty appointment with
      research responsibility at a medical school. In addition, awardees of the Medical
      Fellows Program were not significantly less likely than Medical Scientist
      Training Program (MSTP) and non-MSTP MD-PhD program participants to receive a
      National Institutes of Health postdoctoral award, and awardees of the Cloister
      Program were not significantly less likely than non-MSTP MD-PhD students to
      receive a faculty appointment with research responsibility. Women and
      underrepresented minority students were proportionally represented among awardees
      of the two HHMI programs whereas they were relatively underrepresented in MD-PhD
      programs. CONCLUSIONS: The one-year intensive research training supported by the
      HHMI training programs appears to provide an effective imprinting experience on
      medical students' research careers and to be an attractive strategy for training
      physician-scientists.

PMID- 14660433
TI  - Gender differences among physician-scientists in self-assessed abilities to
      perform clinical research.
AB  - PURPOSE: To examine gender differences in physicians' self-assessed abilities to
      apply knowledge and skills in six core competencies for success as a clinical
      investigator. METHOD: A written questionnaire containing 35 learning objectives
      was administered to physicians involved in a clinical-research training program
      at the University of Wisconsin-Madison. Between 2000 and 2002, 57 postgraduate
      trainees (49% women) completed the questionnaire; 40 of the 57 completed the
      questionnaire a second time after a four-day intensive workshop in clinical
      research. The main outcome measure was gender differences in ratings for each
      question answered. RESULTS: Before the workshop, women physicians rated their
      abilities lower than men rated their own abilities on 22 of 35 learning
      objectives and women were significantly lower in rating their ability to spend
      sufficient time developing and advancing their own area of scientific knowledge
      and research. After the workshop, women rated themselves lower than men rated
      themselves on 33 of 35 objectives, with significant differences in seven. Women
      did not rate themselves significantly higher than men rated themselves on any of
      the 35 objectives assessed. CONCLUSION: Women physicians consistently rated their
      abilities to perform or apply knowledge and skills related to clinical research
      lower than men rated themselves, and a traditional training venue exacerbated
      these gender differences. This previously unexplored gender difference in self
      perceived competency may indicate an additional barrier women face in academic
      career development and suggests that educational programs incorporate learning
      activities that address gender differences when training physicians for careers
      in clinical research.

PMID- 14660434
TI  - BRCA2 deficiency in mice leads to meiotic impairment and infertility.
AB  - The role of Brca2 in gametogenesis has been obscure because of embryonic
      lethality of the knockout mice. We generated Brca2-null mice carrying a human BAC
      with the BRCA2 gene. This construct rescues embryonic lethality and the mice
      develop normally. However, there is poor expression of the transgene in the
      gonads and the mice are infertile, allowing examination of the function of BRCA2
      in gametogenesis. BRCA2-deficient spermatocytes fail to progress beyond the early
      prophase I stage of meiosis. Observations on localization of recombination
      related and spermatogenic-related proteins suggest that the spermatocytes undergo
      early steps of recombination (DNA double strand break formation), but fail to
      complete recombination or initiate spermiogenic development. In contrast to the
      early meiotic prophase arrest of spermatocytes, some mutant oocytes can progress
      through meiotic prophase I, albeit with a high frequency of nuclear
      abnormalities, and can be fertilized and produce embryos. Nonetheless, there is
      marked depletion of germ cells in adult females. These studies provide evidence
      for key roles of the BRCA2 protein in mammalian gametogenesis and meiotic
      success.

PMID- 14660435
TI  - Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle
      progression in cerebellar neuronal precursors.
AB  - Neuronal precursor cells in the developing cerebellum require activity of the
      sonic hedgehog (Shh) and phosphoinositide-3-kinase (PI3K) pathways for growth and
      survival. Synergy between the Shh and PI3K signaling pathways are implicated in
      the cerebellar tumor medulloblastoma. Here, we describe a mechanism through which
      these disparate signaling pathways cooperate to promote proliferation of
      cerebellar granule neuron precursors. Shh signaling drives expression of mRNA
      encoding the Nmyc1 oncoprotein (previously N-myc), which is essential for
      expansion of cerebellar granule neuron precursors. The PI3K pathway stabilizes
      Nmyc1 protein via inhibition of GSK3-dependent Nmyc1 phosphorylation and
      degradation. The effects of PI3K activity on Nmyc1 stabilization are mimicked by
      insulin-like growth factor, a PI3K agonist with roles in central nervous system
      precursor growth and tumorigenesis. These findings indicate that Shh and PI3K
      signaling pathways converge on N-Myc to regulate neuronal precursor cell cycle
      progression. Furthermore, they provide a rationale for therapeutic targeting of
      PI3K signaling in medulloblastoma.

PMID- 14660436
TI  - A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in
      chondrocytes of developing cartilage and osteoarthritic joint cartilage.
AB  - We have identified a novel chordin-like protein, CHL2, which is structurally most
      homologous to CHL/neuralin/ventroptin. When injected into Xenopus embryos, CHL2
      RNA induced a secondary axis. Recombinant CHL2 protein interacted directly with
      BMPs in a competitive manner to prevent binding to the type I BMP receptor
      ectodomain, and inhibited BMP-dependent induction of alkaline phosphatase in
      C2C12 cells. Thus, CHL2 behaves as a secreted BMP-binding inhibitor. In situ
      hybridization revealed that CHL2 expression is restricted to chondrocytes of
      various developing joint cartilage surfaces and connective tissues in
      reproductive organs. Adult mesenchymal progenitor cells expressed CHL2, and its
      levels decreased during chondrogenic differentiation. Addition of CHL2 protein to
      a chondrogenic culture system reduced cartilage matrix deposition. Consistently,
      CHL2 transcripts were weakly detected in normal adult joint cartilage. However,
      CHL2 expression was upregulated in middle zone chondrocytes in osteoarthritic
      joint cartilage (where hypertrophic markers are induced). CHL2 depressed
      chondrocyte mineralization when added during the hypertrophic differentiation of
      cultured hyaline cartilage particles. Thus, CHL2 may play negative roles in the
      (re)generation and maturation of articular chondrocytes in the hyaline cartilage
      of both developing and degenerated joints.

PMID- 14660437
TI  - Xenopus Meis3 protein forms a hindbrain-inducing center by activating FGF/MAP
      kinase and PCP pathways.
AB  - Knockdown studies in Xenopus demonstrated that the XMeis3 gene is required for
      proper hindbrain formation. An explant assay was developed to distinguish between
      autonomous and inductive activities of XMeis3 protein. Animal cap explants
      caudalized by XMeis3 were recombined with explants neuralized by the BMP dominant
      negative receptor protein. XMeis3-expressing cells induced convergent extension
      cell elongations in juxtaposed neuralized explants. Elongated explants expressed
      hindbrain and primary neuron markers, and anterior neural marker expression was
      extinguished. Cell elongation was dependent on FGF/MAP-kinase and Wnt-PCP
      activities. XMeis3 activates FGF/MAP-kinase signaling, which then modulates the
      PCP pathway. In this manner, XMeis3 protein establishes a hindbrain-inducing
      center that determines anteroposterior patterning in the brain.

PMID- 14660438
TI  - Roles for GFRalpha1 receptors in zebrafish enteric nervous system development.
AB  - Components of the zebrafish GDNF receptor complex are expressed very early in the
      development of enteric nervous system precursors, and are already present as
      these cells begin to enter the gut and migrate caudally along its length. Both
      gfra1a and gfra1b as well as ret are expressed at this time, while gfra2
      expression, the receptor component that binds the GDNF-related ligand neurturin,
      is not detected until the precursors have migrated along the gut. Gfra genes are
      also expressed in regions of the zebrafish brain and peripheral ganglia,
      expression domains conserved with other species. Enteric neurons are eliminated
      after injection with antisense morpholino oligonucleotides against ret or against
      both Gfra1 orthologs, but are not affected by antisense oligonucleotides against
      gfra2. Blocking GDNF signaling prevents migration of enteric neuron precursors,
      which remain positioned at the anterior end of the gut. Phenotypes induced by
      injection of antisense morpholinos against both Gfra orthologs can be rescued by
      introduction of mRNA for gfra1a or for gfra2, suggesting that GFRalpha1 and
      GFRalpha2 are functionally equivalent.

PMID- 14660439
TI  - No tail co-operates with non-canonical Wnt signaling to regulate posterior body
      morphogenesis in zebrafish.
AB  - The vertebrate posterior body is formed by a combination of the gastrulation
      movements that shape the head and anterior trunk and posterior specific cell
      behaviors. Here, we investigated whether genes that regulate cell movements
      during gastrulation [no tail (ntl)/brachyury, knypek (kny) and pipetail
      (ppt)/wnt5] interact to regulate posterior body morphogenesis. Both kny;ntl and
      ppt;ntl double mutant embryos exhibit synergistic trunk and tail shortening by
      early segmentation. Gene expression analysis in the compound mutants indicates
      that anteroposterior germ-layer patterning is largely normal and that the tail
      elongation defects are not due to failure to specify or maintain posterior
      tissues. Moreover, ntl interacts with ppt and kny to synergistically regulate the
      posterior expression of the gene encoding bone morphogenetic protein 4 (bmp4) but
      not of other known T-box genes, fibroblast growth factor genes or caudal genes.
      Examination of mitotic and apoptotic cells indicates that impaired tail
      elongation is not simply due to decreased cell proliferation or increased cell
      death. Cell tracing in ppt;ntl and kny;ntl mutants demonstrates that the ventral
      derived posterior tailbud progenitors move into the tailbud. However,
      gastrulation-like convergence and extension movements and cell movements within
      the posterior tailbud are impaired. Furthermore, subduction movements of cells
      into the mesendoderm are reduced in kny;ntl and ppt;ntl mutants. We propose that
      Ntl and the non-canonical Wnt pathway components Ppt and Kny function in
      parallel, partially redundant pathways to regulate posterior body development.
      Our work initiates the genetic dissection of posterior body morphogenesis and
      links genes to specific tail-forming movements. Moreover, we provide genetic
      evidence for the notion that tail development entails a continuation of
      mechanisms regulating gastrulation together with mechanisms unique to the
      posterior body.

PMID- 14660440
TI  - Control of the proliferation versus meiotic development decision in the C.
      elegans germline through regulation of GLD-1 protein accumulation.
AB  - Maintenance of the stem cell population in the C. elegans germline requires GLP
      1/Notch signaling. We show that this signaling inhibits the accumulation of the
      RNA binding protein GLD-1. In a genetic screen to identify other genes involved
      in regulating GLD-1 activity, we identified mutations in the nos-3 gene, the
      protein product of which is similar to the Drosophila translational regulator
      Nanos. Our data demonstrate that nos-3 promotes GLD-1 accumulation redundantly
      with gld-2, and that nos-3 functions genetically downstream or parallel to fbf,
      an inhibitor of GLD-1 translation. We show that the GLD-1 accumulation pattern is
      important in controlling the proliferation versus meiotic development decision,
      with low GLD-1 levels allowing proliferation and increased levels promoting
      meiotic entry.

PMID- 14660441
TI  - Global expression analysis of gene regulatory pathways during endocrine
      pancreatic development.
AB  - To define genetic pathways that regulate development of the endocrine pancreas,
      we generated transcriptional profiles of enriched cells isolated from four
      biologically significant stages of endocrine pancreas development: endoderm
      before pancreas specification, early pancreatic progenitor cells, endocrine
      progenitor cells and adult islets of Langerhans. These analyses implicate new
      signaling pathways in endocrine pancreas development, and identified sets of
      known and novel genes that are temporally regulated, as well as genes that
      spatially define developing endocrine cells from their neighbors. The
      differential expression of several genes from each time point was verified by RT
      PCR and in situ hybridization. Moreover, we present preliminary functional
      evidence suggesting that one transcription factor encoding gene (Myt1), which was
      identified in our screen, is expressed in endocrine progenitors and may regulate
      alpha, beta and delta cell development. In addition to identifying new genes that
      regulate endocrine cell fate, this global gene expression analysis has uncovered
      informative biological trends that occur during endocrine differentiation.

PMID- 14660442
TI  - A cell-specific enhancer that specifies lin-3 expression in the C. elegans anchor
      cell for vulval development.
AB  - During C. elegans vulval development, the anchor cell (AC) in the somatic gonad
      expresses lin-3, activating the EGF receptor signaling pathway in vulval
      precursor cells (VPCs) and thereby inducing and patterning VPCs. Previous studies
      with lin-3 mutants and transgene expression have revealed that the level of LIN-3
      in the AC must be precisely regulated for proper vulval development. To
      understand how lin-3 expression is achieved in the AC, we identified a 59 bp lin
      3 enhancer sufficient to activate lin-3 transcription solely in the AC. The
      enhancer contains two E-box elements, and one FTZ-F1 nuclear hormone receptor
      (NHR) binding site that is mutated in a vulvaless mutant, lin-3(e1417).
      Mutagenesis studies show that both E-boxes and the NHR binding site are necessary
      to express lin-3 in the AC. In vitro DNA-binding studies and in vivo functional
      assays indicate that distinct trans-acting factors, including the E
      protein/Daughterless homolog HLH-2 and unidentified nuclear hormone receptor(s),
      are necessary for lin-3 transcription in the AC and thus are involved in vulval
      development.

PMID- 14660443
TI  - Long term mortality after severe starvation during the siege of Leningrad:
      prospective cohort study.
AB  - OBJECTIVES: To determine whether starvation during periods of increased growth
      after birth have long term health consequences. DESIGN: Analysis of
      cardiovascular risk factors and mortality in a longitudinal follow up after the
      1941-4 siege of Leningrad. Mortality measured from 1975 up to the end of 1999.
      SETTING: St Petersburg, Russia (formerly Leningrad). PARTICIPANTS: 5000 men born
      1916-35 who lived in Leningrad, randomly selected to take part in health
      examinations in 1975-7. Of the 3905 men who participated, a third had experienced
      the siege. MAIN OUTCOME MEASURES: Relative risk of ischaemic heart disease and
      mortality from stroke by siege exposure. Odds ratios and means for several
      cardiovascular risk factors. RESULTS: Three to six decades after the siege, in
      men who experienced the siege around the age of puberty blood pressure was raised
      (mean difference in systolic 3.3 mm Hg, in diastolic 1.3 mm Hg) as was mortality
      from ischaemic heart disease (relative risk 1.39, 95% confidence interval 1.07 to
      1.79) and stroke (1.67, 1.15 to 2.43), including haemorrhagic stroke (1.71, 0.90
      to 3.22). The effect on mortality was partly mediated via blood pressure but not
      by any other measured biological, behavioural, or social factor. CONCLUSIONS:
      Starvation, or accompanying chronic stress, particularly at the onset of or
      during puberty, may increase vulnerability to later cardiovascular disease.

PMID- 14660444
TI  - Ocular surface reconstruction, amniotic membrane, and cultivated epithelial cells
      from the limbus.

PMID- 14660446
TI  - Povidone-iodine prophylaxis of ophthalmia neonatorum.

PMID- 14660447
TI  - Three dimensions of skew deviation.

PMID- 14660448
TI  - Blindness and eye diseases in Tibet: findings from a randomised, population based
      survey.
AB  - BACKGROUND: Public health officials of the Tibet Autonomous Region (TAR) of China
      requested a survey of blindness, eye diseases, and eye care service utilisation
      to assist the development of a 10 year blindness prevention and treatment plan.
      The objective of the survey was to determine the prevalence of blindness and
      visual impairment, as well as cataract surgical coverage and surgical outcome in
      the TAR. METHODS: The Tibet Eye Care Assessment was a cross sectional prevalence
      study of three of the seven prefectures (provinces) of the TAR (Lhoka, Nakchu,
      and Lingzhr) selected to represent its three main environmental regions. The
      survey sample was selected using a random multistage cluster method. Two teams
      conducted the survey in a standardised fashion in each prefecture, Lhoka during
      May and Nakchu during June 1999, and Lingzhr during May 2000. Visual acuity,
      cause of vision loss, trachoma, and vitamin A deficiency were included in the
      clinical examination. RESULTS: Among the 15,900 people enumerated, 12,644 were
      examined for an overall response rate of 79.6%. The crude prevalence of blindness
      (presenting better eye visual acuity of less than 6/60) was 2.3%; age and sex
      adjusted blindness prevalence was 1.4% (95% CI 1.3 to 1.5). Visual impairment
      (better eye presenting visual acuity of 6/24 to 6/60) was found in 10.9% (95% CI
      10.5 to 11.2) of the population (age and sex adjusted). Cataract was the primary
      cause of blindness (50.7%), followed by macular degeneration (12.7%) and corneal
      opacity (9.7%). CONCLUSION: Blindness is a serious public health problem in
      Tibet, with prevalence higher than in similar studies in eastern China. As
      elsewhere in the world, women have an excess burden of blindness compared to men.
      About 75% of blindness in Tibet can be either prevented or treated. Eye care
      planning for Tibet must focus on cataract, particularly among women.

PMID- 14660449
TI  - A double application approach to ophthalmia neonatorum prophylaxis.
AB  - AIMS: To investigate if a second drop of 2.5% povidone-iodine ophthalmic solution
      placed within the first postnatal day would achieve better prophylaxis against
      ophthalmia neonatorum than a single drop applied at birth. METHODS: A masked,
      prospective, controlled trial was conducted over a 2 year period in a Kenyan
      hospital. Randomisation was achieved by alternating weeks of one or two eye drop
      application to both eyes. All 719 neonates received one drop of the povidone
      iodine solution to both eyes at birth, while 317 received a second drop at
      hospital discharge or 24 (SD 4) hours after delivery, whichever was first. All
      infants developing conjunctivitis within a month after birth underwent
      microbiological analysis using Gram and Giemsa stains, direct fluorescent
      antibody assay for Chlamydia trachomatis, and culture. RESULTS: Of the neonates
      receiving the one eye drop application, 18.4% returned with a red eye with
      discharge, 4.0% had organisms found on the initial smear, and 8.2% had a positive
      culture. The corresponding proportions for the multidrop group were 24.3%, 4.7%,
      and 10.4%. Of those returning with an inflamed eye, there were no cases of
      Neisseria gonorrhoeae, 4.2% in the single dose group and 3.9% in the double dose
      group were positive for C trachomatis, and 5.4% and 6.5% respectively for
      Staphylococcus aureus. At discharge, the eyelid oedema score of the double dose
      group was mildly greater than the single dose group (1.4 (0.67) v 1.2 (0.73),
      p=0.0002). There was no statistically significant difference between the groups
      in any other category. CONCLUSION: There is no advantage to administering
      povidone-iodine prophylaxis against ophthalmia neonatorum twice in the first
      postnatal day over a single application at birth.

PMID- 14660450
TI  - Choroidal vascular remodelling in central serous chorioretinopathy after
      indocyanine green guided photodynamic therapy with verteporfin: a novel treatment
      at the primary disease level.
AB  - AIMS: To evaluate the changes in the choroidal vasculature in central serous
      chorioretinopathy (CSC) after photodynamic therapy (PDT) with verteporfin and to
      assess its potential role as a treatment option. METHODS: A prospective, non
      comparative, interventional study was performed in eyes with persistent CSC or
      chronic CSC that had fluorescein leakage at the fovea. All eyes received one
      single session of PDT with verteporfin (6 mg/m2 body surface area) followed by
      application of 50 J/cm2 laser at 689 nm. The laser spot size was guided by
      findings in ICG-A. RESULTS: Six eyes from six patients with a mean follow up of
      12.7 months were analysed. Narrowing of the original dilated choroidal vessels
      and decrease in extravascular leakage could be demonstrated in all (100%) PDT
      treated eyes. 3 months after PDT, the mean diameter of the dilated choroidal
      vessel reduced from 546 microm to 371 microm (p=0.028). Five (83%) patients had
      improvement in visual symptoms and best corrected visual acuity. Fluorescence
      leakage stopped at the 1 month follow up in five eyes (83%) and at 3 months in
      all six eyes (100%). One eye developed choroidal neovascularisation at 3 month
      follow up. There was no other serious ocular or systemic complication.
      CONCLUSIONS: PDT is successful in stopping the fluorescein leakage in all six
      patients without recurrence of CSC. The ICG-A findings of choroidal vascular
      remodelling and decreased choroidal permeability after PDT are encouraging. As
      the sample size is small and the mean follow up period is short, further trials
      of PDT with verteporfin for CSC are required to address the optimal parameters in
      ensuring longer term safety and efficacy outcome.

PMID- 14660452
TI  - Comparison of outcomes of primary and secondary implantation of scleral fixated
      posterior chamber intraocular lens.
AB  - AIM: To assess and compare the results of primary and secondary implantation of
      scleral fixated posterior chamber intraocular lens (SFIOL). METHODS: The medical
      records of a consecutive series of 55 eyes of 55 patients with SFIOLs implanted
      during (group 1) or after (group 2) complicated senile cataract surgery were
      retrospectively reviewed and analysed. RESULTS: There were 30 and 25 eyes in
      group 1 and 2, respectively. Follow up was from 6 to 36 months. Mean logMAR
      postoperative best corrected visual acuity in group 1 was not significantly
      different (0.50 (SD 0.36)) from that of group 2 (0.36 (0.21)) (p=0.109).
      Postoperative best corrected visual acuity of 6/12 or better was achieved in
      58.6% and 76.0% in group 1 and 2, respectively. The difference was not
      statistically significant (p=0.177). In group 1, 25 (83.3%) eyes had a total of
      55 early complications, while in group 2, 16 (64%) eyes had 26 early
      complications (p=0.028). The difference in early complication was statistically
      significant. For late complication after 1 month, 21 (70.0%) eyes had a total of
      37 complications in group 1, while 13 eyes (52.0%) had 19 complications in group
      2 (p=0.077). The difference in late complication was not statistically
      significant. CONCLUSION: Secondary implantation of SFIOL after cataract
      extraction seems to have a lower early complication rate than primary
      implantation in complicated cataract extraction although the final visual acuity
      and late complication rate are not significantly different.

PMID- 14660453
TI  - Contrast sensitivity improves after brimonidine therapy in primary open angle
      glaucoma: a case for neuroprotection.
AB  - AIMS: To determine the visual outcome following initiation of brimonidine therapy
      in glaucoma. METHODS: 16 newly diagnosed previously untreated glaucoma patients
      were randomly assigned to either timolol 0.5% or brimonidine 0.2%. Visual acuity,
      contrast sensitivity (CS), visual fields, intraocular pressure (IOP), blood
      pressure, and heart rate were evaluated at baseline and after 3 months. RESULTS:
      IOP reduction was similar for both groups (p<0.05). Brimonidine improved CS; in
      the right eye at 6 and 12 cpd (p=0.043, p=0.017); in the left eye at 3 and 12 cpd
      (p=0.044, p=0.046). Timolol reduced CS at 18 cpd in the right eye (p=0.041).
      There was no change in any other measured parameters. CONCLUSION: Glaucoma
      patients exhibit improved CS on initiation of brimonidine therapy.

PMID- 14660454
TI  - Fluorescein and indocyanine green angiography findings in Behcet's disease.
AB  - AIM: To evaluate and compare the fluorescein (FA) and indocyanine green
      angiographic (ICGA) findings, and to investigate the choroidal involvement in
      Behcet's disease. METHODS: FA and ICGA were performed on 112 eyes of 62 patients
      with Behcet's disease, between November 1993 and July 2002, using Topcon IMAGEnet
      Digital System. Patients were aged 16-50 years; 48 (77.4%) were male and 14
      (22.6%) were female. RESULTS: FA showed dye leakage from retinal vessels in 57
      (50.9%) eyes, cystoid macular oedema in 18 eyes (16.1%), optic disc oedema in
      four eyes (3.6%), disc neovascularisation in three eyes (2.7%), and retinal
      neovascularisation in two eyes (1.8%). ICGA showed hyperfluorescent lesions in 40
      eyes (35.7%), hypofluorescent lesions in 17 eyes (15.2%), hyperfluorescent and
      hypofluorescent lesions in 12 (10.7%) eyes, ICG leakage from choroidal vessels in
      11 eyes (9.8%), irregular filling of choriocapillaris in five eyes (4.5%), and
      choroidal filling defect in four eyes (3.6%). Hyperfluorescent and
      hypofluorescent lesions which were seen in 53 out of 69 eyes (76.8%) on ICGA,
      were not visible on FA. 55 eyes (49.1%) showed hyperfluorescence on the disc on
      both FA and ICGA, whereas 36 (32.1%) showed hyperfluorescence only on FA.
      CONCLUSION: The hyperfluorescence and/or hypofluorescence, irregular filling of
      the choriocapillaris, choroidal filling defect, and ICG leakage from choroidal
      vessels seen only on ICGA may suggest choroidal involvement in Behcet's disease.

PMID- 14660455
TI  - Scanning laser Doppler flowmeter study of retinal blood flow in macular area of
      healthy volunteers.
AB  - AIM: To compare the interocular and intraocular differences of capillary
      perfusion, and the intraocular regional differences of retinal blood flow in the
      macular area of healthy volunteers. METHODS: Tissue blood flow in the macula was
      examined in both eyes of 20 healthy volunteers with the Heidelberg retinal
      flowmeter. Blood flow measurements were made in a 10 degrees x 2.5 degrees area
      superior and inferior to the macula. The mean blood flow (MBF) was calculated by
      an automatic full field perfusion image analyser program. The MBF in the right
      and left eyes and in the superior and inferior macular areas of the same eye were
      compared. RESULTS: The ratios of the MBF in the right eye to the left eye in the
      macular areas were 1.00, and 1.03, respectively. The ratio of the MBF in the
      superior macular area to the inferior area was 1.01 for the right eyes and 1.04
      for the left eyes. CONCLUSIONS: Because no significant differences were found in
      the MBF between the two eyes and between the superior and inferior macular areas
      in the same eye, interocular (for example, affected eye versus fellow eye) and
      intraocular (superior versus inferior macular areas) comparisons of MBF can be
      made to determine if changes in retinal perfusion have occurred.

PMID- 14660456
TI  - Semiautomated computer analysis of vessel growth in preterm infants without and
      with ROP.
AB  - AIMS: To measure characteristics of the retinal blood vessels close to the optic
      disc in full term and preterm infants, with and without retinopathy of
      prematurity (ROP), using digital imaging. To determine whether these measures are
      indicative of the presence or severity of ROP in the retinal periphery. METHODS:
      52 digital fundus images from 42 babies were analysed with a semiautomated
      analysis program developed at Imperial College London. Analysis was limited to
      the principal temporal vessels close to the optic disc: recording venular
      diameter and arteriolar diameter and tortuosity. RESULTS: Each result was
      categorised by the gestational age of the infant ("very premature" 24-27 weeks,
      "moderately premature" 28-31 weeks, and "near term" > or =32 weeks) and by the
      highest stage of ROP present ("no ROP," "mild ROP" stage 1 or 2, and "severe ROP"
      stage 3). Arteriolar tortuosity was found to vary significantly (Kruskal-Wallis
      p=0.002) with ROP severity. Although venular and arteriolar diameters increased
      monotonically with ROP severity the differences were not significant. Venular
      diameter, arteriolar diameter, and arterial tortuosity did not vary significantly
      between gestational age groups. CONCLUSIONS: This study confirms it is possible
      to quantify the size and tortuosity of retinal blood vessels in term and preterm
      babies using digital image analysis software. This method detected significant
      increases in arteriolar tortuosity with increasing ROP severity.

PMID- 14660458
TI  - Is manual counting of corneal endothelial cell density in eye banks still
      acceptable? The French experience.
AB  - AIM: To examine the differences in manual endothelial cell counting methods in
      French eye banks and to analyse whether these differences could explain some
      substantial discrepancies observed in endothelial cell density (ECD) for corneas
      made available for transplant. METHODS: A questionnaire was sent to the 22 eye
      banks asking for details of the technical features of the light microscopes used,
      the microscope calibration, strategy for cell counting, the technical staff, and
      the method of presenting endothelial data. RESULTS: All eye banks responded and
      91% (20/22) used only manual counting methods, in real time, directly through a
      microscope, and 62 different technicians, with varying experience, were involved
      in such counting. Counting of cells within the borders of a grid that were in
      contact with two adjacent borders was the most common method (17/22, 77%). Of the
      eight banks (8/22, 36%) that did not calibrate their microscopes, six reported
      the highest ECD values. Of the 14 others (64%), six applied a "magnification
      correcting factor" to the initial cell counts. In five of these cases, the
      corrected ECD was lower than estimated on initial count. Most of the banks
      (12/22, 55%) counted 100 cells or less in one to six non-adjacent zones of the
      mosaic. 14 of the banks (14/22, 64%) also graded cell polymegethism while seven
      (7/22, 32%) also graded pleomorphism ("hexagonality"). CONCLUSIONS: Lack of
      microscope calibration appears to be the leading cause of variance in ECD
      estimates in French eye banks. Other factors such as differences in counting
      strategy, the evaluation of smaller numbers of cells, and the different extent of
      experience of the technicians may also contribute to intraobserver and
      interobserver variability. Further comparative studies, including cross checking
      and the outcome of repeated counts from manual methods, are clearly needed with
      cross calibration to a computer based image archiving and analysis system.

PMID- 14660457
TI  - Unrecordable pulsatile ocular blood flow may signify severe stenosis of the
      ipsilateral internal carotid artery.
AB  - AIM: To examine the relation between stenosis of the internal carotid artery
      (ICA) and pulsatile ocular blood flow (POBF). METHODS: In 57 eyes of 30 patients
      who were referred for Doppler ultrasound examination of the ICA we measured POBF
      and analysed the correlation with degree of ipsilateral ICA stenosis. RESULTS:
      There was a significant negative correlation between POBF and ipsilateral ICA
      stenosis (Pearson correlation coefficient, r=-0.516, p<0.0001). In 14 eyes POBF
      could not be measured by the OBF tonometer, and in 11 of these cases (79%) severe
      stenosis (>75%) of the ipsilateral ICA was present. When these eyes were excluded
      from analysis, there was no correlation between POBF and ICA stenosis (r=-0.02,
      p=0.91). Among these 43 eyes in which POBF could be measured it ranged 667-2095
      microl/min with a mean of 970.72 microl/min. CONCLUSION: Low or unrecordable POBF
      may signify severe stenosis of the internal carotid artery. POBF is not a direct
      reflection of ipsilateral ICA blood flow.

PMID- 14660459
TI  - Association between lower optic nerve laser Doppler blood volume measurements and
      glaucomatous visual field progression.
AB  - AIM: To perform a preliminary assessment of the relation between optic nerve
      circulatory parameters and glaucomatous visual field progression. METHODS: This
      study included 29 eyes of 23 patients with open angle glaucoma that had typical
      glaucomatous nerve fibre bundle visual field defects and increased cup to disc
      ratios. Laser Doppler flowmetry (Oculix) was used to measure relative optic nerve
      blood volume (Vol), velocity (Vel) and flow in the superior temporal (ST) and
      inferior temporal (IT) neuroretinal rim of the optic nerve. After blood flow
      measurements patients were followed for 6-62 months (mean 33 (SD 17) months) and
      2-11 Humphrey visual fields (4.7 (2.6) fields) were obtained. Progression of
      glaucoma was assessed by the slope of the corrected pattern standard deviation
      (CPSD) values versus time, which was calculated manually for each eye using
      regression analysis. RESULTS: A significant negative correlation was observed
      between Vol in the IT rim and the CPSD slope (r=-0.56, p=0.002); patients with
      lower Vol tended to show faster progression of glaucomatous field damage than
      those with higher Vol. When the eyes were arbitrarily divided into two groups
      according to lower Vol (0.32 (0.06) arbitrary units, AU, n=15) or higher Vol
      (0.49 (0.06) AU, n=14), those with lower Vol had significantly worse mean CPSD
      slopes (0.50 (0.48) dB/year) than those with higher Vol (-0.67 (1.38) dB/year;
      Student's t test, p=0.009). CONCLUSIONS: In the IT rim, the area most prone to
      develop glaucomatous field damage, lower Vol is associated with subsequently
      faster CPSD progression. These measurements suggest that circulatory
      abnormalities may have a role in the development of glaucoma.

PMID- 14660460
TI  - Intraocular pressure after replacement of current dual therapy with latanoprost
      monotherapy in patients with open angle glaucoma.
AB  - AIMS: To evaluate the efficacy and safety of replacing current dual ocular
      hypotensive therapy with latanoprost 0.005% monotherapy in patients with open
      angle glaucoma. METHODS: This randomised, open label, parallel group,
      multinational study included 466 patients with open angle glaucoma currently on
      dual ocular hypotensive therapy, including a beta adrenergic receptor antagonist.
      Patients were assigned (1:3) to ongoing dual therapy or a switch to monotherapy
      with latanoprost 0.005% once daily for 6 months. Intraocular pressure (IOP) was
      measured at 10 am and 5 pm at baseline, month 3, and month 6. Groups were
      compared for differences in diurnal IOP change, IOP success rates (IOP < or =22
      mm Hg with < or =15% increase from baseline), and clinical success rates (not
      requiring change in therapy). RESULTS: Baseline mean diurnal IOP was 17.8 (SD
      2.0) mm Hg in the latanoprost group and 17.6 (2.1) mm Hg in the dual therapy
      group. After 6 months, mean diurnal IOP was reduced by 0.26 (0.18) (SEM 1.4%) mm
      Hg (p=0.153) in the group switched to latanoprost and by 0.37 (0.25) (2.1%) mm Hg
      (p=0.138) in those continuing dual therapy (difference: 0.11 mm Hg; p=0.641).
      Success rates defined by IOP criteria were 83% for latanoprost and 89% for
      continued dual therapy (difference: 6%; p=0.122). Clinical success rates were 97%
      for latanoprost and 99% for dual therapy (difference: 2%; p=0.161). Ocular
      adverse events were reported by 23% of patients in both treatment groups.
      CONCLUSION: Latanoprost monotherapy is a safe and effective alternative for many
      patients with open angle glaucoma requiring dual topical ocular hypotensive
      therapy for IOP control.

PMID- 14660462
TI  - Evaluation of the measurement of refractive error by the PowerRefractor: a
      remote, continuous and binocular measurement system of oculomotor function.
AB  - BACKGROUND/AIM: The technique of photoretinoscopy is unique in being able to
      measure the dynamics of the oculomotor system (ocular accommodation, vergence,
      and pupil size) remotely (working distance typically 1 metre) and objectively in
      both eyes simultaneously. The aim of this study was to evaluate clinically the
      measurement of refractive error by a recent commercial photoretinoscopic device,
      the PowerRefractor (PlusOptiX, Germany). METHOD: The validity and repeatability
      of the PowerRefractor was compared to: subjective (non-cycloplegic) refraction on
      100 adult subjects (mean age 23.8 (SD 5.7) years) and objective autorefraction
      (Shin-Nippon SRW-5000, Japan) on 150 subjects (20.1 (4.2) years). Repeatability
      was assessed by examining the differences between autorefractor readings taken
      from each eye and by re-measuring the objective prescription of 100 eyes at a
      subsequent session. RESULTS: On average the PowerRefractor prescription was not
      significantly different from the subjective refraction, although quite variable
      (difference +0.05 (0.63) D, p=0.41) and more negative than the SRW-5000
      prescription (by -0.20 (0.72) D, p<0.001). There was no significant bias in the
      accuracy of the instrument with regard to the type or magnitude of refractive
      error. The PowerRefractor was found to be repeatable over the prescription range
      of -8.75D to +4.00D (mean spherical equivalent) examined. CONCLUSION: The
      PowerRefractor is a useful objective screening instrument and because of its
      remote and rapid measurement of both eyes simultaneously is able to assess the
      oculomotor response in a variety of unrestricted viewing conditions and patient
      types.

PMID- 14660461
TI  - Palladium-103 plaque radiation therapy for macular degeneration: results of a 7
      year study.
AB  - AIM: To report 7 year results of ophthalmic plaque radiotherapy for exudative
      macular degeneration. METHODS: In a phase I clinical trial, 30 patients (31 eyes)
      were treated with ophthalmic plaque irradiation for subfoveal exudative macular
      degeneration. Radiation was delivered to a mean 2 mm from the inner sclera (range
      1.2-2.4) prescription point calculated along the central axis of the plaque. The
      mean prescription dose was 17.62 Gy (range 12.5-24) delivered over 34 hours
      (range 18-65). Early Treatment Diabetic Retinopathy Study (ETDRS) type
      standardised visual acuity determinations, ophthalmic examinations, and
      angiography were performed before and after treatment. Clinical evaluations were
      performed in a non-randomised and unmasked fashion. RESULTS: At 33.3 months
      (range 3-4), 17 of 31 (55%) eyes had lost 3 or more lines of vision on the ETDRS
      chart, five (16%) had improved 3 or more lines, and the remaining nine (29%) were
      within 2 lines of their pretreatment visual acuity measurement. Overall, 45% of
      patients were within or improved more than 2 lines of their initial visual
      acuity. Five eyes developed macular scars, eight developed subsequent
      neovascularisation or haemorrhage, and three progressed through therapy. Two
      patients were lost to follow up. The most common finding of patients followed for
      6 or more months (n=18 of 29 (62%)) was regression or stabilisation of the
      exudative process. No radiation retinopathy, optic neuropathy, or cataracts could
      be attributed to irradiation. CONCLUSION: Ophthalmic plaque radiation can be used
      to treat exudative macular degeneration. At the dose and dose rates employed,
      most patients experienced decreased exudation or stabilisation of their maculas.
      No sight limiting radiation complications were noted during 7 year follow up.
      Owing to the variable natural course of this disease, a prospective randomised
      clinical trial should be performed to evaluate the efficacy of plaque radiation
      therapy for exudative macular degeneration.

PMID- 14660463
TI  - Corneal stromal changes following reconstruction by ex vivo expanded limbal
      epithelial cells in rabbits with total limbal stem cell deficiency.
AB  - AIM: To study corneal stromal changes and the presence of myofibroblasts after
      transplantation of ex vivo expanded limbal epithelium. METHODS: A state of limbal
      deficiency was induced in 16 rabbits. After transplantation with autologous ex
      vivo expanded limbal epithelium on amniotic membrane (AM), their clinical
      outcomes were classified as success, partial success or failure according to
      surface smoothness, stromal clarity, and vascularisation. Clinical outcomes were
      correlated with phenotypic outcomes of corneal, conjunctival, or mixed
      epithelium, defined by expression of K3 keratin or MUC5AC. Immunostaining was
      performed with antibodies against collagen IV, fibronectin, and alpha-smooth
      muscle actin (alpha-SMA) to assess stromal wound remodelling. RESULTS: Rabbits
      were sacrificed after a mean follow up of 10 (SD 3.3) months. Collagen IV,
      expressed in the basement membrane of all three groups, was found in the stroma
      of the partial success, but not in that of the success or the failure.
      Fibronectin was absent in the success and the failure, but expressed in the
      stroma of the partial success. Alpha-SMA was expressed in superficial stroma of
      the partial success, but suppressed in areas with AM remnants. CONCLUSION:
      Restoration of a clear and transparent cornea is associated with a normal corneal
      epithelium and complete wound remodelling. In contrast, wound healing remains
      active and incomplete in conjunctivalised corneas, which remain opaque with
      myofibroblasts.

PMID- 14660464
TI  - Development of organised conjunctival leucocyte aggregates after corneal
      transplantation in rats.
AB  - AIM: To investigate the development of lymphoid aggregates in the conjunctiva
      after corneal transplantation in rats. METHODS: LEW or PVG strain corneas were
      transplanted orthotopically to PVG rats. Cornea and conjunctiva were examined
      clinically for up to 42 days. Eyes were removed with attached conjunctiva on days
      10 and 15 after transplantation (before and during rejection), together with
      normal eyes, fixed, paraffin embedded, and examined immunohistochemically.
      RESULTS: Clinically, the temporal half of the upper palpebral conjunctiva of
      recipients of 10/19 allografts and 1/10 isografts developed pronounced swelling,
      correlating with inflammation and rejection. Histologically, the swelling
      comprised leucocytic aggregates with an altered overlying epithelium. Aggregates
      contained granulocytes, macrophages, and cells expressing major
      histocompatibility complex (MHC) class II, CD4, and CD8, all more numerous in
      allograft associated conjunctiva. Class II+ cells were more abundant at the
      surface, whereas macrophages and T cells were more numerous in the deeper stroma.
      There were few B cells. There was greater CD54 expression by vascular endothelium
      in allograft associated aggregates. Cells expressing TNFalpha and IFNgamma but
      not IL1beta were present in stromal and superficial areas. CONCLUSIONS: Corneal
      transplantation in rats induces the development of organised conjunctival
      leucocytic aggregates in a fixed location that are significantly more pronounced
      in recipients of allografts compared with isografts and show characteristics of a
      Th1 type immune response. These aggregates have characteristics of conjunctiva
      associated lymphoid tissue and may be sites of presentation of graft antigens and
      lymphocyte proliferation at the ocular surface.

PMID- 14660466
TI  - Staining of the ILM in macular surgery.

PMID- 14660468
TI  - What sets the long-term level of sympathetic nerve activity: is there a role for
      arterial baroreceptors?
AB  - Much of our knowledge of the influence of the sympathetic nervous system on the
      control of blood pressure is built on experimental approaches that focus very
      much on time scales <24 h. Although direct recordings of sympathetic nerve
      activity (SNA) over short time scales provide important information, it is
      difficult to place their relevance over the longer term where the development of
      chronic changes in blood pressure are likely to be a mixture of hormonal, renal,
      and neural influences. Recently new experimental approaches are now revealing a
      possible role for arterial baroreceptors in the chronic regulation of SNA. These
      studies reveal that chronic increases in blood pressure are associated with
      chronic changes in SNA that may be due to nonresetting of the blood pressure-SNA
      baroreflex relationship. This review discusses the implications of such
      information, highlighting new technologies for long-term recording of SNA that
      appear to hold much promise for revealing the role of SNA to the kidney for the
      long-term control of blood pressure.

PMID- 14660465
TI  - How much blue light should an IOL transmit?
AB  - Older, and even some modern, intraocular lenses (IOLs) transmit potentially
      hazardous ultraviolet radiation (UVR) to the retina. In addition, IOLs transmit
      more blue and green light to the retina for scotopic vision than the crystalline
      lenses they replace, light that is also potentially hazardous. The severity of
      UVR-blue type phototoxicity increases with decreasing wavelength, unlike the
      action spectrum of blue-green type retinal phototoxicity and the luminous
      efficiency of scotopic vision which both peak in the blue-green part of the
      optical spectrum around 500 nm. Theoretically, UVR+blue absorbing IOLs provide
      better retinal protection but worse scotopic sensitivity than UVR-only absorbing
      IOLs, but further study is needed to test this analysis. UVR is potentially
      hazardous and not useful for vision, so it is prudent to protect the retina from
      it with chromophores in IOLs. Determining authoritatively how much blue light an
      optimal IOL should block requires definitive studies to determine (1) the action
      spectrum of the retinal phototoxicity potentially involved in human retinal
      ageing, and (2) the amount of shorter wavelength blue light required for older
      adults to perform essential activities in dimly lit environments.

PMID- 14660469
TI  - Dopamine and food reward: back to the elements.

PMID- 14660470
TI  - Regulation of body fat content?

PMID- 14660471
TI  - What do "eating peptides" really control? Potent stimulation of food acquisition
      by AgRP.

PMID- 14660472
TI  - Persistent photoperiodic effects on immunological responsiveness: shedding light
      on immunity.

PMID- 14660473
TI  - Linkage between insulin and the free radical theory of aging.

PMID- 14660474
TI  - The vestibular system and cardiovascular responses to altered gravity.

PMID- 14660475
TI  - Of fish, fat, and fuel: fatty acid transport in trout muscle.

PMID- 14660476
TI  - Inactivation of the DMH selectively inhibits the ACTH and corticosterone
      responses to hypoglycemia.
AB  - We have previously reported that repeated bouts of insulin-induced hypoglycemia
      (IIH) in the rat result in blunted activation of the paraventricular, arcuate,
      and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been
      implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA)
      responses to stressors, we hypothesized that its blunted activation may play a
      role in the impaired counterregulatory response that is also observed with
      repeated bouts of IIH. In the present study, we evaluated the role of normal DMH
      activation in the counterregulatory response to a single bout of IIH. Local
      infusion of lidocaine (n = 8) to inactivate the DMH during a 2-h bout of IIH
      resulted in a significant overall decrease of the ACTH response and a delay of
      onset of the corticosterone response compared with vehicle-infused controls (n =
      9). We observed suppression of the ACTH response at time (t) = 90 and 120 min (50
      +/- 12 and 63 +/- 6%, respectively, of control levels) and early suppression of
      the corticosterone response at t = 30 min (59 +/- 13% of the control level). The
      epinephrine, norepinephrine, and glucagon responses were not altered by DMH
      inactivation. Our finding suggests that DMH inactivation may play a specific role
      in decreasing the HPA axis response after repeated bouts of IIH.

PMID- 14660477
TI  - Jejunal administration of linoleic acid increases activity of neurons in the
      paraventricular nucleus of the hypothalamus.
AB  - The present experiment examined whether neurons located in the paraventricular
      nucleus of the hypothalamus (PVN) respond to intestinal infusions of long-chain
      fatty acids. Single-unit recordings were made of neurons located in and adjacent
      to the PVN during jejunal administration of linoleic acid. Jejunal administration
      of linoleic acid increased single-unit activity of neurons located in the PVN but
      did not affect activity of neurons located in adjacent tissue outside the PVN.
      The largest increases in neuronal activity were observed in the anterior PVN (0.9
      1.3 mm posterior to bregma) compared with the posterior PVN (1.8-2.1 mm posterior
      to bregma). Jejunal administration of saline failed to affect activity of neurons
      located either inside or outside the PVN. When the same neurons were subsequently
      tested for their response to intravenous administration of 2 microg/kg of CCK-8,
      excitatory responses were more frequently observed than inhibitory responses, but
      both types of responses were observed regardless of whether neurons were located
      inside or outside the PVN. In addition, there was no strong correlation between
      the magnitude of the neuronal response evoked by jejunal administration of
      linoleic acid compared with intravenous CCK-8. These data suggest that neurons
      located in the anterior PVN may play a role in the mediation of suppression of
      food intake produced by intestinal administration of lipids.

PMID- 14660478
TI  - Effect of ribose supplementation on resynthesis of adenine nucleotides after
      intense intermittent training in humans.
AB  - The effect of oral ribose supplementation on the resynthesis of adenine
      nucleotides and performance after 1 wk of intense intermittent exercise was
      examined. Eight subjects performed a random double-blind crossover design. The
      subjects performed cycle training consisting of 15 x 10 s of all-out sprinting
      twice per day for 7 days. After training the subjects received either ribose (200
      mg/kg body wt; Rib) or placebo (Pla) three times per day for 3 days. An exercise
      test was performed at 72 h after the last training session. Immediately after the
      last training session, muscle ATP was lowered (P < 0.05) by 25 +/- 2 and 22 +/-
      3% in Pla and Rib, respectively. In both Pla and Rib, muscle ATP levels at 5 and
      24 h after the exercise were still lower (P < 0.05) than pretraining. After 72 h,
      muscle ATP was similar (P > 0.05) to pretraining in Rib (24.6 +/- 0.6 vs. 26.2 +/
      0.2 mmol/kg dry wt) but still lower (P < 0.05) in Pla (21.1 +/- 0.5 vs. 26.0 +/-
      0.2 mmol/kg dry wt) and higher (P < 0.05) in Rib than in Pla. Plasma hypoxanthine
      levels after the test performed at 72 h were higher (P < 0.05) in Rib compared
      with Pla. Mean and peak power outputs during the test performed at 72 h were
      similar (P > 0.05) in Pla and Rib. The results support the hypothesis that the
      availability of ribose in the muscle is a limiting factor for the rate of
      resynthesis of ATP. Furthermore, the reduction in muscle ATP observed after
      intense training does not appear to be limiting for high-intensity exercise
      performance.

PMID- 14660479
TI  - Skin surface cooling improves orthostatic tolerance in normothermic individuals.
AB  - Previous studies suggest that skin surface cooling (SSC) preserves orthostatic
      tolerance; however, this hypothesis has not been experimentally tested. Thus the
      purpose of this project was to identify whether SSC improves orthostatic
      tolerance in otherwise normothermic individuals. Eight subjects underwent two
      presyncope limited graded lower-body negative pressure (LBNP) tolerance tests. On
      different days, and randomly assigned, LBNP tolerance was assessed under control
      conditions and during SSC (perfused 16 degrees C water through tube-lined suit
      worn by each subject). Orthostatic tolerance was significantly elevated in each
      individual due to SSC, as evidenced by a significant increase in a standardized
      cumulative stress index (normothermia 564 +/- 58 mmHg.min; SSC 752 +/- 58
      mmHg.min; P < 0.05). At most levels of LBNP, blood pressure during the SSC
      tolerance test was significantly greater than during the control test.
      Furthermore, the reduction in cerebral blood flow velocity was attenuated during
      some of the early stages of LBNP for the SSC trial. Plasma norepinephrine
      concentrations were significantly higher during LBNP with SSC, suggesting that
      SSC may improve orthostatic tolerance through increased sympathetic activity.
      These data demonstrate that SSC is effective in improving orthostatic tolerance
      in otherwise normothermic individuals.

PMID- 14660480
TI  - Effects of leptin administration on lactational infertility in food-restricted
      rats depend on milk delivery.
AB  - Leptin administration has been shown to prevent the disruptive effects of acute
      food deprivation on reproductive function in cycling females and lactating
      females. We examined the ability of intracerebroventricular leptin administration
      to ameliorate the effects of food restriction for the first 2 wk postpartum on
      length of lactational infertility. Leptin administration did not reduce the
      effects of food restriction on reproductive function at either time period (days
      8-15 and 15-22 postpartum) or dose (1 and 10 microg/day) administered. Because of
      the sharp contrast between these results and the ability of leptin to offset the
      effects of acute food deprivation in lactating rats, the remaining studies
      investigated the possible causes of this difference. Both central and peripheral
      leptin administration eliminated food deprivation-induced prolongation of
      lactational infertility, suggesting that neither route of administration nor dose
      was a factor. However, we noticed that, whereas chronically food-restricted
      females continue to deliver milk to their young, acutely food-deprived females do
      not. To test the hypothesis that the continued energetic drain of milk production
      and delivery might prevent the ability of exogenous leptin administration to
      eliminate the effects of undernutrition, leptin was administered to food
      restricted, lactating rats prevented from delivering milk. In this situation
      intracerebroventricular leptin treatment completely eliminated the effects of
      food restriction on lactational infertility, suggesting that leptin contributes
      to the maintenance of reproductive function via two pathways: direct binding in
      the central nervous system and through increasing the availability of oxidizable
      metabolic fuels.

PMID- 14660481
TI  - Leukocytic cell sources of airway tissue kallikrein.
AB  - Lung tissue kallikrein (TK) is a serine proteinase that putatively plays a role
      in the pathophysiology of asthma by generating kallidin and bradykinin, mediators
      that contribute to airway hyperresponsiveness. In previous studies we observed
      biphasic increases in TK activity in bronchoalveolar lavage fluid following
      airway allergen challenge in allergic sheep. Although glandular TK is likely a
      major source of the initial increase in TK, the sources of the late increases in
      TK that are associated with the development of airway hyperresponsiveness may be
      dependent on activated resident and recruited inflammatory cells including
      alveolar macrophages (AMs) and neutrophils (PMNs). These cells increase
      concomitantly with the late increases in TK activity. To test this hypothesis, we
      obtained AMs from bronchoalveolar lavage fluid and PMNs and monocytes (precursors
      of AMs) from sheep blood and determined whether these cells contained TK and
      whether these same cells could release TK upon activation. Using confocal
      microscopy, immunocytochemical techniques, and enzyme activity assays, we found
      that all three cell types contained and secreted TK. All three cell types
      demonstrated basal release of TK, which could be increased after stimulation with
      zymosan. In addition, PMNs also released TK in the presence of phorbol ester,
      suggesting multiple secretory pathways in these cells. Furthermore, we showed
      that human monocytes also contain and secrete TK. We conclude that in the
      airways, monocytes, PMNs, and AMs may contribute to increased TK activity.
      Knowing the sources of TK in the airways could be important in understanding the
      mechanisms of inflammation that contribute to the pathophysiology of asthma and
      may help in the development of new therapies to control the disease.

PMID- 14660482
TI  - Airway responsiveness after acute exposure to urban particulate matter 1648 in a
      DO11.10 murine model.
AB  - Enhanced airway responsiveness (AR) is a well-established characteristic of
      asthma that epidemiological evidence has linked with inhalation of ambient
      particulate matter (PM). To determine whether acute exposure to urban particulate
      matter PM1648 can exacerbate airway responsiveness and alter the early
      inflammatory state, a unique murine model was created using DO11.10 mice,
      transgenic for a T cell receptor recognizing ovalbumin(323-339). Because these
      mice are sensitive to ovalbumin, immunization procedures involving adjuvant or
      long aerosolization procedures are not necessary and, therefore, allow for the
      study of an acute AR response to particulate and antigen in young animals. AR was
      assessed by barometric whole body plethysmography and measured by enhanced pause
      (Penh). PM1648 and ovalbumin were administered intranasally 72 and 4 h before to
      AR assessment, respectively. A dose-response relationship between PM1648 and Penh
      was determined, and doses at or above 500 microg had Penh values significantly
      higher than saline controls. Penh values of control particle titanium dioxide
      (TiO(2)) were similar to saline controls demonstrating no nonspecific particulate
      effect on AR. Lung lavage at time of AR assessment showed no significant
      inflammation due to particulate exposure or ovalbumin alone; however,
      PM1648/ovalbumin and TiO(2)/ovalbumin combinations resulted in significant
      neutrophilia. In addition, treatment with polymyxin B to remove surface-bound
      endotoxin did not significantly affect Penh levels. These results indicate that
      PM1648 specifically increases AR in a dose-dependent manner and that this
      exacerbation is not a direct response to increased neutrophil concentration,
      particle-bound endotoxin or nonspecific particle effects.

PMID- 14660483
TI  - Conditional expression of transforming growth factor-alpha in adult mouse lung
      causes pulmonary fibrosis.
AB  - To determine whether overexpression of transforming growth factor (TGF)-alpha in
      the adult lung causes remodeling independently of developmental influences, we
      generated conditional transgenic mice expressing TGF-alpha in the epithelium
      under control of the doxycycline (Dox)-regulatable Clara cell secretory protein
      promoter. Two transgenic lines were generated, and following 4 days of Dox
      induction TGF-alpha levels in whole lung homogenate were increased 13- to 18-fold
      above nontransgenic levels. After TGF-alpha induction, transgenic mice developed
      progressive pulmonary fibrosis and body weight loss, with mice losing 15% of
      their weight after 6 wk of TGF-alpha induction. Fibrosis was detected within 4
      days of TGF-alpha induction and developed initially in the perivascular,
      peribronchial, and pleural regions but later extended into the interstitium.
      Fibrotic regions were composed of increased collagen and cellular proliferation
      and were adjacent to airway and alveolar epithelial sites of TGF-alpha
      expression. Fibrosis progressed in the absence of inflammatory cell infiltrates
      as determined by histology, without changes in bronchiolar alveolar lavage total
      or differential cell counts and without changes in proinflammatory cytokines TNF
      alpha or IL-6. Active TGF-beta in whole lung homogenate was not altered 1 and 4
      days after TGF-alpha induction, and immunostaining was not increased in the
      peribronchial/perivascular areas at all time points. Chronic epithelial
      expression of TGF-alpha in adult mice caused progressive pulmonary fibrosis
      associated with increased collagen and extracellular matrix deposition and
      increased cellular proliferation. Induction of pulmonary fibrosis by TGF-alpha
      was independent of inflammation or early activation of TGF-beta.

PMID- 14660484
TI  - Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis.
AB  - Apoptosis(programmed cell death) is induced in pulmonary cells and contributes to
      the pathogenesis of acute lung injury in septic humans. Previous studies have
      shown that nitric oxide (NO) is an important modulator of apoptosis; however, the
      functional role of NO derived from inducible NO synthase (iNOS) in sepsis-induced
      pulmonary apoptosis remains unknown. We measured pulmonary apoptosis in a rat
      model of Escherichia coli lipopolysaccharide (LPS)-induced sepsis in the absence
      and presence of the selective iNOS inhibitor 1400W. Four groups were studied 24 h
      after saline (control) or LPS injection in the absence and presence of 1400W
      pretreatment. Apoptosis was evaluated using DNA fragmentation, terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and
      caspase activation. LPS administration significantly augmented pulmonary cell
      apoptosis and caspase-3 activity in airway and alveolar epithelial cells.
      Pretreatment with 1400W significantly enhanced LPS-induced pulmonary apoptosis
      and increased caspase-3 and -7 activation. The antiapoptotic effect of iNOS was
      confirmed in iNOS-/- mice, which developed a greater degree of pulmonary
      apoptosis both under control conditions and in response to LPS compared with wild
      type mice. By comparison, genetic deletion of the neuronal NOS had no effect on
      LPS-induced pulmonary apoptosis. We conclude that NO derived from iNOS plays an
      important protective role against sepsis-induced pulmonary apoptosis.

PMID- 14660485
TI  - Retinoic acid inhibits interleukin-4-induced eotaxin production in a human
      bronchial epithelial cell line.
AB  - Retinoic acid (RA) is known to accelerate wound healing and induce cell
      differentiation. All-trans RA (ATRA) exerts its effect by binding retinoic acid
      receptors, which are members of the nuclear receptor family. We investigated
      whether RA can alter expression of eotaxin, a potent eosinophil chemoattractant
      that is regulated by the transcription factors signal transducer and activator of
      transcription 6 (STAT6) and NF-kappaB. We examined the effects of RA on eotaxin
      expression in a human bronchial epithelial cell line BEAS-2B. ATRA and its
      stereodimer 9-cis retinoic acid (9-cis RA) inhibited IL-4-induced release of
      eotaxin at 10(-6) M by 78.0 and 52.0%, respectively (P < 0.05). ATRA and 9-cis RA
      also significantly inhibited IL-4-induced eotaxin mRNA expression at 10(-6) M by
      52.3 and 53.5%, respectively (P < 0.05). In contrast, neither ATRA nor 9-cis RA
      had any effects on TNF-alpha-induced eotaxin production. In transfection studies
      using eotaxin promoter luciferase plasmids, the inhibitory effect of ATRA on IL-4
      induced eotaxin production was confirmed at the transcriptional level.
      Interestingly, ATRA had no effects on IL-4-induced tyrosine phosphorylation,
      nuclear translocation, or DNA binding activity of STAT6. Activating protein-1 was
      not involved in ATRA-mediated transrepression of eotaxin with IL-4 stimulation.
      The mechanism of the inhibitory effect of ATRA on IL-4-induced eotaxin production
      in human bronchial epithelial cells has not been elucidated but does not appear
      to be due to an effect on STAT6 activation. These findings raise the possibility
      that RA may reduce eosinophilic airway inflammation, one of the prominent
      pathological features of allergic diseases such as bronchial asthma.

PMID- 14660486
TI  - Role of cGMP-dependent protein kinase in development of tolerance to nitric oxide
      in pulmonary veins of newborn lambs.
AB  - Continuous exposure to nitrovasodilators and nitric oxide induces tolerance to
      their vasodilator effects in vascular smooth muscle. This study was done to
      determine the role of cGMP-dependent protein kinase (PKG) in the development of
      tolerance to nitric oxide. Isolated fourth-generation pulmonary veins of newborn
      lambs were studied. Incubation of veins for 20 h with DETA NONOate (DETA NO; a
      stable nitric oxide donor) significantly reduced their relaxation response to the
      nitric oxide donor and to beta-phenyl-1,N2-etheno-8-bromo-cGMP (8-Br-PET-cGMP, a
      cell-permeable cGMP analog). Incubation with DETA NO significantly reduced PKG
      activity and protein and mRNA levels in the vessels. These effects were prevented
      by 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (an inhibitor of soluble guanylyl
      cyclase) and Rp-8-Br-PET-cGMPS (an inhibitor of PKG). A decrease in PKG protein
      and mRNA levels was also observed after continuous exposure to cGMP analogs. The
      PKG inhibitor abrogated these effects. The decrease in cGMP-mediated relaxation
      and in PKG activity caused by continuous exposure to DETA NO was not affected by
      KT-5720, an inhibitor of cAMP-dependent protein kinase. Prolonged exposure to 8
      Br-cAMP (a cell-permeable cAMP analog) did not affect PKG protein level in the
      veins. These results suggest that continuous exposure to nitric oxide or cGMP
      downregulates PKG by a PKG-dependent mechanism. Such a negative feedback
      mechanism may contribute to the development of tolerance to nitric oxide in
      pulmonary veins of newborn lambs.

PMID- 14660487
TI  - Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil
      kinetics during acute lung injury.
AB  - We measured neutrophil glucose uptake with positron emission tomographic imaging
      and [18F]fluorodeoxyglucose ([18F]FDG-PET) in anesthetized dogs after intravenous
      oleic acid-induced acute lung injury (ALI; OA group, n = 6) or after low-dose
      intravenous endotoxin (known to activate neutrophils without causing lung injury)
      followed by OA (Etx + OA group, n = 7). The following two other groups were
      studied as controls: one that received no intervention (n = 5) and a group
      treated with Etx only (n = 6). PET imaging was performed 1.5 h after initiating
      experimental interventions. The rate of [3H]deoxyglucose ([3H]DG) uptake was also
      measured in vitro in cells recovered from bronchoalveolar lavage (BAL) performed
      after PET imaging. Circulating neutrophil counts fell significantly in animals
      treated with Etx but not in the other two groups. The rate of [18F]FDG uptake,
      measured by the influx constant Ki, was significantly elevated (P < 0.05) in both
      Etx-treated groups (7.9 +/- 2.6 x 10(-3) ml blood x ml lung(-1) x min(-1) in the
      Etx group, 9.3 +/- 4.8 x 10(-3) ml blood x ml lung(-1) x min(-1) in the Etx + OA
      group) but not in the group treated only with OA (3.4 +/- 0.8 x 10-3 ml blood x
      ml lung(-1) x min(-1)) when compared with the normal control (1.6 +/- 0.4 x 10(
      3) ml blood x ml lung(-1) x min(-1)). [3H]DG uptake was increased (73 +/- 7%) in
      BAL neutrophils recovered from the Etx + OA group (P < 0.05) but not in the OA
      group. Ki and [3H]DG uptake rates were linearly correlated (R2 = 0.65). We
      conclude that the rate of [18F]FDG uptake in the lungs during ALI reflects the
      state of neutrophil activation. [18F]FDG-PET imaging can detect pulmonary
      sequestration of activated neutrophils, despite the absence of alveolar
      neutrophilia. Thus [18F]FDG-PET imaging may be a useful tool to study neutrophil
      kinetics during ALI.

PMID- 14660488
TI  - p38 MAP kinase-mediated negative inotropic effect of HIV gp120 on cardiac
      myocytes.
AB  - Myocardial dysfunction leading to dilated cardiomyopathy has been documented with
      surprisingly high frequency in human immunodeficiency virus (HIV)-infected
      individuals. p38 MAP kinase has been implicated as a mediator of myocardial
      dysfunction. We previously reported p38 MAP kinase activation by the HIV coat
      protein gp120 in neonatal rat cardiac myocytes. We now report the direct
      inotropic effects of HIV gp120 on adult rat ventricular myocytes (ARVM). ARVM
      were continuously superfused with gp120, and percent fractional shortening (FS)
      was determined by automated border detection and simultaneous intracellular
      ionized free Ca2+ concentration ([Ca2+]i) measured by fura 2-AM fluorescence:
      gp120 alone increased FS and increased [Ca2+]i within 5 min and then depressed FS
      without a decrease in [Ca2+]i by 20-60 min, which persisted for at least 2 h.
      Exposure of ARVM to gp120 also resulted in the phosphorylation of the upstream
      regulator of p38 MAP kinase MKK3/6, p38 MAP kinase itself, and its downstream
      effector, ATF-2, over a similar time course. ERK (p44/42) and JNK stress
      signaling pathways were not similarly activated. The effects of the p38 MAP
      kinase inhibitor were concentration dependent. SB-203580 (10 microM) blocked both
      p38 MAP kinase phosphorylation and the delayed negative inotropic effect of
      gp120. SB-203580 (5 microM) selectively blocked phosphorylation of ATF-2 without
      blocking the phosphorylation of MKK3/6 or p38 MAP kinase itself. SB-203580 (5
      microM) administered before, with, or after gp120 blocked the negative inotropic
      effect of gp120 in ARVM. p38 MAP kinase activation may be a common stress
      response mechanism contributing to myocardial dysfunction in HIV and other
      nonischemic as well as ischemic cardiomyopathies.

PMID- 14660489
TI  - Chloride-dependent calcium transients induced by angiotensin II in vascular
      smooth muscle cells.
AB  - Cl- is essential for the vasoconstrictive response to angiotensin II (ANG II). In
      vascular smooth muscle cells (VSMC), we determined whether ANG II-induced
      transient increase in intracellular Ca2+ concentration ([Ca2+]i) is Cl-
      dependent. After incubating the cells at different extracellular Cl-
      concentration ([Cl-]e) for 40 min, the ANG II-induced Ca2+ transients at 120
      meq/l Cl- were more than twice those at either 80 or 20 meq/l Cl-. Replacing Cl-
      with bicarbonate or gluconate yielded similar results. In addition, after removal
      of extracellular Ca2+, ANG II-induced as well as platelet-derived growth factor
      induced Ca2+ release exhibited Cl- dependency. The difference of Ca2+ release
      with high vs. low [Cl-]e was not affected by acutely altering [Cl-]e 1 min before
      administration of ANG II when [Cl-]i was yet to be equilibrated with [Cl-]e.
      Pretreatment of a Cl- channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic
      acid, increased ANG II-induced Ca2+ release and entry at 20 meq/l Cl- but did not
      alter those at 120 meq/l Cl-. However, after equilibration, a reduced [Cl-]e did
      not affect thapsigargin-induced Ca2+ release, suggesting that Cl- may not affect
      the size of intracellular Ca2+ stores. Nevertheless, at high [Cl-], the peak
      increase of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] induced by ANG II was
      approximately sixfold that at low [Cl-]. Thus the Cl- -dependent effects of ANG
      II on Ca2+ transients may be mediated, at least in part, by a Cl- -dependent
      Ins(1,4,5)P3 accumulation in VSMC.

PMID- 14660490
TI  - Oxygen sensing in health and disease.

PMID- 14660491
TI  - Eating, exercise, and "thrifty" genotypes: connecting the dots toward an
      evolutionary understanding of modern chronic diseases.
AB  - Survival of Homo sapiens during evolution was dependent on the procurement of
      food, which in turn was dependent on physical activity. However, food supply was
      never consistent. Thus it is contended that the ancient hunter-gatherer had
      cycles of feast and famine, punctuated with obligate periods of physical activity
      and rest. Hence, gene selection in the Late-Paleolithic era was probably
      influenced by physical activity and rest. To ensure survival during periods of
      famine, certain genes evolved to regulate efficient intake and utilization of
      fuel stores. Such genes were termed "thrifty genes" in 1962. Furthermore,
      convincing evidence shows that this ancient genome has remained essentially
      unchanged over the past 10,000 years and certainly not changed in the past 40-100
      years. Although the absolute caloric intake of modern-day humans is likely lower
      compared with our hunter-gatherer ancestors, it is nevertheless in positive
      caloric balance in the majority of the US adult population mainly due to the
      increased sedentary lifestyle in present society. We contend that the combination
      of continuous food abundance and physical inactivity eliminates the
      evolutionarily programmed biochemical cycles emanating from feast-famine and
      physical activity-rest cycles, which in turn abrogates the cycling of certain
      metabolic processes, ultimately resulting in metabolic derangements such as
      obesity and Type 2 diabetes. In this context, we postulate that perhaps a crucial
      mechanism to break the stall of the metabolic processes would be via exercise
      through the regulation of "physical activity genes," some of which may also be
      potential candidates for the "thrifty genes" of our hunter-gatherer ancestors.
      Therefore, the identification of such "thrifty gene" candidates would help
      provide insight into the pathogenetic processes of the numerous physical
      inactivity-mediated disorders.

PMID- 14660492
TI  - Electrical stimulation of the posteromedial thalamus modulates breathing in
      unanesthetized fetal sheep.
AB  - Having previously shown that lesions in the posteromedial group of thalamic
      nuclei abolish hypoxic inhibition of fetal breathing, we devised this study to
      identify thalamic loci that depress breathing by focal stimulation of specific
      sectors of the caudal thalamus and adjacent structures. Multipolar electrode
      arrays consisting of a series of eight stimulation contacts at 1.25-mm intervals
      were implanted vertically through guide cannulae into the caudal diencephalon of
      12 chronically catheterized fetal sheep (>0.8 term), and central neural tissue
      was stimulated between adjacent contacts. Each site was stimulated repeatedly
      with increasing current searching for spatial and stimulus strength parameters
      for a reliable alteration in respiratory rate. Respiratory period increased when
      stimulation involved areas of the parafascicular nuclear complex (Pf), which more
      than doubled the mean period compared with the baseline of 0.90 +/- 0.19 s. The
      change in respiratory period was due to an increase in expiratory time, whereas
      inspiratory time and breath amplitude were not significantly affected. Breathing
      period and expiratory time were also increased when the stimulations involved the
      intralaminar wing surrounding the mediodorsal nucleus, the rostral central gray,
      zona incerta, and ventral tegmental area. Reductions in respiratory frequency
      occurred less consistently, with stimulation involving surrounding zones
      including the sub-Pf, ventromedial nucleus, and ventrobasal nuclear complex.
      These findings support the hypothesis that a restricted area of the posteromedial
      thalamus (principally Pf) constitutes part of a neuronal circuitry that modulates
      respiratory motoneurons.

PMID- 14660493
TI  - Deep breath reversal and exponential return of methacholine-induced obstruction
      in asthmatic and nonasthmatic subjects.
AB  - A deep breath (DB) during induced obstruction results in a transient reversal
      with a return to pre-DB levels in both asthmatic and nonasthmatic subjects. The
      time course of this transient recovery has been reported to be exponential by one
      group but linear by another group. In the present study, we estimated airway
      resistance (Raw) from measurements of respiratory system transfer impedance
      before and after a DB. Nine healthy subjects and nine asthmatic subjects were
      studied at their maximum response during a methacholine challenge. In all
      subjects, the DB resulted in a rapid decrease in Raw, which then returned to pre
      DB levels. This recovery was well fit with a monoexponential function in both
      groups, and the time constant was significantly smaller in the asthmatic than the
      nonasthmatic subjects (11.6 +/- 5.0 and 35.1 +/- 15.9 s, respectively).
      Obstruction was completely reversed in the nonasthmatic subjects (pre- and
      postchallenge mean Raw immediately after the DB were 2.03 +/- 0.66 and 2.06 +/-
      0.68 cmH2O.l-1.s, respectively), whereas in the asthmatic subjects complete
      reversal did not occur (2.29 +/- 0.78 and 4.84 +/- 2.64 cmH2O.l-1.s,
      respectively). Raw after the DB returned to postchallenge, pre-DB values in the
      nonasthmatic subjects (3.78 +/- 1.56 and 3.97 +/- 1.63 cmH2O.l-1.s,
      respectively), whereas in the asthmatic subjects it was higher but not
      significantly so (9.19 +/- 4.95 and 7.14 +/- 3.56 cmH2O.l-1.s, respectively). The
      monoexponential recovery suggests a first-order process such as airway wall
      parenchymal tissue interdependence or renewed constriction of airway smooth
      muscle.

PMID- 14660494
TI  - Interstitial albumin concentration measured during growth of perivascular cuffs
      in liquid-filled rabbit lung.
AB  - The growth rate and albumin concentration of interstitial fluid cuffs were
      measured in isolated rabbit lungs inflated with albumin solution (3 g/dl) to
      constant airway (Paw) and vascular pressures for up to 10 h. Cuff size was
      measured from images of frozen lung sections, and cuff albumin concentration (Cc)
      was measured from the fluorescence of Evans blue labeled albumin that entered the
      cuffs from the alveolar space. At 5-cmH2O Paw, cuff size peaked at 1 h and then
      decreased by 75% in 2 h. The decreased cuff size was consistent with an osmotic
      absorption into the albumin solution that filled the vascular and alveolar
      spaces. At 15-cmH2O Paw, cuff size peaked at 0.25 h and then remained constant.
      Cc rose continuously at both pressures, but was greater at the higher pressure.
      The increasing Cc with a constant cuff size was modeled as diffusion through
      epithelial pores. Initial Cc-to-airway albumin concentration ratio was 0.1 at 5
      cmH2O Paw and increased to 0.3 at 15 cmH2O, a behavior that indicated an
      increased permeability with lung inflation. Estimated epithelial reflection
      coefficient was 0.9 and 0.7, and equivalent epithelial pore radii were 4.5 and
      6.1 nm at 5- and 15-cmH2O Paw, respectively. The initial cuff growth occurred
      against an albumin colloid osmotic pressure gradient because a high interstitial
      resistance reduced the overall epithelial-interstitial reflection coefficient to
      the low value of the interstitium.

PMID- 14660495
TI  - The respiratory change in preejection period: a new method to predict fluid
      responsiveness.
AB  - The accuracy and clinical utility of preload indexes as bedside indicators of
      fluid responsiveness in patients after cardiac surgery is controversial. This
      study evaluates whether respiratory changes (Delta) in the preejection period
      (PEP; DeltaPEP) predict fluid responsiveness in mechanically ventilated patients.
      Sixteen postcoronary artery bypass surgery patients, deeply sedated under
      mechanical ventilation, were enrolled. PEP was defined as the time interval
      between the beginning of the Q wave on the electrocardiogram and the upstroke of
      the radial arterial pressure. DeltaPEP (%) was defined as the difference between
      expiratory and inspiratory PEP measured over one respiratory cycle. We also
      measured cardiac output, stroke volume index, right atrial pressure, pulmonary
      arterial occlusion pressure, respiratory change in pulse pressure, systolic
      pressure variation, and the Deltadown component of SPV. Data were measured
      without positive end-expiratory pressure (PEEP) and after application of a PEEP
      of 10 cmH2O (PEEP10). When PEEP10 induced a decrease of >15% in mean arterial
      pressure value, then measurements were re-performed before and after volume
      expansion. Volume loading was done in eight patients. Right atrial pressure and
      pulmonary arterial occlusion pressure before volume expansion did not correlate
      with the change in stroke volume index after the fluid challenge. Systolic
      pressure variation, DeltaPEP, Deltadown, and change in pulse pressure before
      volume expansion correlated with stroke volume index change after fluid challenge
      (r2 = 0.52, 0.57, 0.68, and 0.83, respectively). In deeply sedated, mechanically
      ventilated patients after cardiac surgery, DeltaPEP, a new method, can be used to
      predict fluid responsiveness and hemodynamic response to PEEP10.

PMID- 14660496
TI  - Oxygen sensing: applications in humans.
AB  - Our concepts of oxygen sensing have been transformed over the years. We now
      appreciate that oxygen sensing is not a unique property limited to
      "chemoreceptors" but is a common property of tissues and that responses to
      changes in oxygen levels are not static but can change over time. Respiratory
      responses initiated at the carotid body are modified by the excitatory and
      depressant effects of hypoxia at the brain and on the pathways connecting the
      carotid body to the brain. Equally important is that we are beginning to use our
      understanding of the cellular and molecular pathways triggered by hypoxia and
      hyperoxia to identify therapeutic targets to treat diseases such as cancer. We
      also have a better understanding of the complexities of the human respiratory
      responses to hypoxia; however, major deficiencies remain in our ability to alter
      or even measure human ventilatory responses to oxygen deficiency.

PMID- 14660497
TI  - Peripheral chemoreceptors in health and disease.
AB  - Peripheral chemoreceptors (carotid and aortic bodies) detect changes in arterial
      blood oxygen and initiate reflexes that are important for maintaining homeostasis
      during hypoxemia. This mini-review summarizes the importance of peripheral
      chemoreceptor reflexes in various physiological and pathophysiological
      conditions. Carotid bodies are important for eliciting hypoxic ventilatory
      stimulation in humans and in experimental animals. In the absence of carotid
      bodies, compensatory upregulation of aortic bodies as well as other
      chemoreceptors contributes to the hypoxic ventilatory response. Peripheral
      chemoreceptors are critical for ventilatory acclimatization at high altitude.
      They also contribute in part to the exercise-induced hyperventilation, especially
      with submaximal and heavy exercise. During pregnancy, hypoxic ventilatory
      sensitivity increases, perhaps due to the actions of estrogen and progesterone on
      chemoreceptors. Augmented peripheral chemoreceptors have been implicated in early
      stages of recurrent apneas, congestive heart failure, and certain forms of
      hypertension. It is likely that chemoreceptors tend to maintain oxygen
      homeostasis and act as a defense mechanism to prevent the progression of the
      morbidity associated with these diseases. Experimental models of recurrent
      apneas, congestive heart failure, and hypertension offer excellent opportunities
      to unravel the cellular mechanisms associated with altered chemoreceptor
      function.

PMID- 14660498
TI  - Oxygen-sensing neurons in the central nervous system.
AB  - This mini-review summarizes the present knowledge regarding central oxygen
      chemosensitive sites with special emphasis on their function in regulating
      changes in cardiovascular and respiratory responses. These oxygen-chemosensitive
      sites are distributed throughout the brain stem from the thalamus to the medulla
      and may form an oxygen-chemosensitive network. The ultimate effect on respiratory
      or sympathetic activity presumably depends on the specific neural projections
      from each of these brain stem oxygen-sensitive regions as well as on the
      developmental age of the animal. Little is known regarding the cellular
      mechanisms involved in the chemotransduction process of the central oxygen
      sensors. The limited information available suggests some conservation of
      mechanisms used by other oxygen-sensing systems, e.g., carotid body glomus cells
      and pulmonary vascular smooth muscle cells. However, major gaps exist in our
      understanding of the specific ion channels and oxygen sensors required for
      transducing central hypoxia by these central oxygen-sensitive neurons. Adaptation
      of these central oxygen-sensitive neurons during chronic or intermittent hypoxia
      likely contributes to responses in both physiological conditions (ascent to high
      altitude, hypoxic conditioning) and clinical conditions (heart failure, chronic
      obstructive pulmonary disease, obstructive sleep apnea syndrome, hypoventilation
      syndromes). This review underscores the lack of knowledge about central oxygen
      chemosensors and highlights real opportunities for future research.

PMID- 14660499
TI  - Oxygen sensing in health and disease.

PMID- 14660500
TI  - Autonomic microganglion cells: a source of acetylcholine in the rat carotid body.
AB  - Hypoxic chemosensitivity of peripheral arterial chemoreceptors and the
      ventilatory response to O2 deprivation increases with postnatal development.
      Multiple putative neurotransmitters, which are synthesized in the carotid body
      (CB), are thought to mediate signals generated by hypoxia. Acetylcholine (ACh) is
      believed to be a major excitatory neurotransmitter participating in hypoxic
      chemosensitivity. However, it is not known whether ACh originates from type I
      cells in the CB. In these studies, we tested the hypothesis that choline
      acetyltransferase (ChAT) and vesicular ACh transporter (VAChT) mRNAs are
      expressed in the CB and that mRNA levels would increase with postnatal maturation
      or exposure to hypoxia. Semiquantitative in situ hybridization histochemistry and
      immunohistochemistry were used to localize cholinergic markers within neurons and
      cells of the rat CB, the nodose-petrosal-jugular ganglion complex, and the
      superior cervical ganglion up to postnatal day 28. We show that the pattern of
      distribution, in tissue sections, is similar for both ACh markers; however, the
      level of VAChT mRNA is uniformly greater than that of ChAT. VAChT mRNA and
      immunoreactivity are detected abundantly in the nodose-petrosal-jugular ganglion
      complex in a number of microganglion cells embedded in nerve fibers innervating
      the CB for all postnatal groups, whereas ChAT mRNA is detected in only a few of
      these cells. Contrary to our hypothesis, postnatal maturation caused a reduction
      in ACh trait expression, whereas hypoxic exposure did not induce the upregulation
      of VAChT and ChAT mRNA levels in the CB, microganglion, or within the ganglion
      complex. The present findings indicate that the source of ACh in the CB is likely
      within autonomic microganglion cells and cholinergic nerve terminals.

PMID- 14660501
TI  - Whole-body hypoxic preconditioning protects mice against acute hypoxia by
      improving lung function.
AB  - Survival in severe hypoxia such as occurs in high altitude requires previous
      acclimatization, which is acquired over a period of days to weeks. It was unknown
      whether intrinsic mechanisms existed that could be rapidly induced and could
      exert immediate protection on unacclimatized individuals against acute hypoxia.
      We found that mice pretreated with whole-body hypoxic preconditioning (WHPC, 6
      cycles of 10-min hypoxia-10-min normoxia) survived significantly longer than
      control animals when exposed to lethal hypoxia (5% O2, survival time of 33.2 +/-
      6.1 min vs. controls at 13.8 +/- 1.2 min, n = 10, P < 0.005). This protective
      mechanism became operative shortly after WHPC and remained effective for at least
      8 h. Accordingly, mice subjected to WHPC demonstrated improved gas exchange when
      exposed to sublethal hypoxia (7% O2, arterial blood Po2 of 49.9 +/- 4.2 vs.
      controls at 39.7 +/- 3.6 Torr, n = 6, P < 0.05), reduced formation of pulmonary
      edema (increase in lung water of 0.491 +/- 0.111 vs. controls at 0.894 +/- 0.113
      mg/mg dry tissue, n = 10, P < 0.02), and decreased pulmonary vascular
      permeability (lung lavage albumin of 7.63 +/- 0.63 vs. controls at 18.24 +/- 3.39
      mg/dl, n = 6-10, P < 0.025). In addition, the severity of cerebral edema caused
      by exposure to sublethal hypoxia was also reduced after WHPC (increase in brain
      water of 0.254 +/- 0.052 vs. controls at 0.491 +/- 0.034 mg/mg dry tissue, n =
      10, P < 0.01). Thus WHPC protects unacclimatized mice against acute and otherwise
      lethal hypoxia, and this protection involves preservation of vital organ
      functions.

PMID- 14660502
TI  - Spinal reciprocal inhibition in human locomotion.
AB  - The purpose of this paper was to study spinal inhibition during several different
      motor tasks in healthy human subjects. The short-latency, reciprocal inhibitory
      pathways from the common peroneal (CP) nerve to the soleus muscle and from the
      tibial nerve to the tibialis anterior muscle were studied as a depression of
      ongoing voluntary electromyograph (EMG) activity. First, the effect of stimulus
      intensity on the amount of inhibition was examined to decide an appropriate
      stimulation to study the task-dependent modulation of inhibition. Then, the
      inhibition at one level of stimulation (1.5 x motor threshold) was investigated
      during standing, walking, and running. The change in slope of inhibition vs. EMG
      level, which approximates the fraction of ongoing activity that is inhibited,
      decreased with CP stimulation from 0.52 during standing to 0.30 during fast
      walking (6 km/h) to 0.17 during running at 9 km/h. Similarly, the slope decreased
      with tibial nerve stimulation from 0.68 (standing) to 0.42 (fast walking) to 0.35
      (running at 9 km/h). All differences, except the last one, were highly
      significant (P < 0.01, Student's t-test). However, the difference between walking
      (0.42) and running (0.36) at the same speed (6 km/h) was not significant with
      tibial nerve stimulation and only significant at P < 0.05 with CP nerve
      stimulation (0.30, 0.20). Also, the difference between standing (0.52) and slow
      walking (3 km/h; 0.41) with CP stimulation was not significant, but it was
      significant (P < 0.01) with tibial nerve stimulation (0.68, 0.49). In conclusion,
      our findings indicate that spinal reciprocal inhibition decreases substantially
      with increasing speed and only changes to a lesser extent with task.

PMID- 14660503
TI  - Hypertrophy of chronically unloaded muscle subjected to resistance exercise.
AB  - In an effort to simulate the compromised function and atrophy of lower limb
      muscles experienced by astronauts after spaceflight, 21 men and women age 30-56
      yr were subjected to unilateral lower limb unloading for 5 wk. Whereas 10 of
      these subjects performed unilateral knee extensor resistance exercise (ULRE) two
      or three times weekly, 11 subjects (UL) refrained from training. The exercise
      regimen consisted of four sets of seven maximal actions, using an apparatus that
      offers concentric and eccentric resistance by utilizing the inertia of rotating
      flywheel(s). Knee extensor muscle strength was measured before and after UL and
      ULRE, and knee extensor and ankle plantar flexor muscle volumes were determined
      by means of magnetic resonance imaging. Surface electromyographic activity
      measured after UL inferred increased muscle use to perform a given motor task. UL
      induced an 8.8% decrease (P < 0.05) in knee extensor muscle volume. After ULRE
      and as a result of only approximately 16 min of maximal contractile activity over
      the 5-wk course, muscle volume increased 7.7% (P < 0.05). Muscle strength
      decreased 24-32% (P < 0.05) in response to UL. Group ULRE showed maintained (P >
      0.05) strength. Ankle plantar flexor muscle volume of the unloaded limb decreased
      (P < 0.05) in both groups (UL 10.5%; ULRE 11.1%). In neither group did the right
      weight-bearing limb show any change (P > 0.05) in muscle volume or strength. The
      results of this study provide evidence that resistance exercise not only may
      offset muscle atrophy but is in fact capable of promoting marked hypertrophy of
      chronically unloaded muscle.

PMID- 14660504
TI  - Effects of estrogen and progesterone administration on extracellular fluid.
AB  - To determine the effect of estrogen and progesterone on plasma volume (PV) and
      extracellular fluid volume (ECFV), we suppressed endogenous estrogen and
      progesterone by using the gonadotropin-releasing hormone (GnRH) antagonist
      ganirelix acetate in seven healthy women (22 +/- 1 yr). Subjects were
      administered GnRH antagonist for 16 days. Beginning on day 5 of GnRH antagonist
      administration, subjects were administered estrogen (E(2)) for 11 days, and
      beginning on day 12 of GnRH antagonist administration, subjects added
      progesterone (E(2)-P(4)) for 4 days. On days 2, 9, and 16 of GnRH antagonist
      administration, we estimated ECFV (inulin washout), transcapillary escape rate of
      albumin (TER(alb)), and PV (Evans blue dye). Plasma E(2) concentration increased
      from 17.9 +/- 4.5 (GnRH antagonist) to 195.9 +/- 60.1 (E(2), P < 0.05) to 245.6
      +/- 62.9 pg/ml (E(2)-P(4), P < 0.05). Compared with GnRH antagonist (1.3 +/- 0.5
      ng/ml), plasma P(4) concentration was unchanged during E(2) (0.9 +/- 0.3 ng/ml)
      and increased to 9.4 +/- 3.1 ng/ml during E(2)-P(4) (P < 0.05). Both E(2) (44.1
      +/- 3.1 ml/kg) and E(2)-P(4) (47.7 +/- 2.8 ml/kg) increased PV compared with GnRH
      antagonist (42.8 +/- 1.3 ml/kg, P < 0.05). Within-subjects TER(alb) was a strong
      negative predictor of PV (mean r = 0.92 +/- 0.03, P < 0.05), and TER(alb) was
      lowest during E(2)-P(4) (5.7 +/- 0.5, 4.1.0 +/- 1.1, and 2.8 +/- 0.9%/h, P <
      0.05, for GnRH antagonist, E(2), and E(2)-P(4), respectively). ECFV was reduced
      during E(2) (227 +/- 31 ml/kg, P < 0.05) compared with both GnRH antagonist (291
      +/- 37 ml/kg) and E(2)-P(4) (283 +/- 19 ml/kg). Thus the percentage of
      extracellular fluid in the plasma compartment increased to 21.0% (P < 0.05)
      during E(2) compared with GnRH antagonist (16.1%) and E(2)-P(4) (17.2%)
      administration. Thus E(2) increased PV via actions on the capillary endothelium
      to lower TER(alb) and favor intravascular water retention, whereas during E(2)
      P(4) PV increased via the combined responses of ECFV expansion and lower
      TER(alb).

PMID- 14660505
TI  - Circulating plasma VEGF response to exercise in sedentary and endurance-trained
      men.
AB  - The skeletal muscle capillary supply is an important determinant of maximum
      exercise capacity, and it is well known that endurance exercise training
      increases the muscle capillary supply. The muscle capillary supply and exercise
      induced angiogenesis are regulated in part by vascular endothelial growth factor
      (VEGF). VEGF is produced by skeletal muscle cells and can be secreted into the
      circulation. We investigated whether there are differences in circulating plasma
      VEGF between sedentary individuals (Sed) and well-trained endurance athletes (ET)
      at rest or in response to acute exercise. Eight ET men (maximal oxygen
      consumption: 63.8 +/- 2.3 ml x kg(-1) x min(-1); maximum power output: 409.4 +/-
      13.3 W) and eight Sed men (maximal oxygen consumption: 36.3 +/- 2.1 ml x kg(-1) x
      min(-1); maximum power output: 234.4 +/- 13.3 W) exercised for 1 h at 50% of
      maximum power output. Antecubital vein plasma was collected at rest and at 0, 2,
      and 4 h postexercise. Plasma VEGF was measured by ELISA analysis. Acute exercise
      significantly increased VEGF at 0 and 2 h postexercise in ET subjects but did not
      increase VEGF at any time point in Sed individuals. There was no difference in
      VEGF between ET and Sed subjects at any time point. When individual peak
      postexercise VEGF was analyzed, exercise did increase VEGF independent of
      training status. In conclusion, exercise can increase plasma VEGF in both ET
      athletes and Sed men; however, there is considerable variation in the individual
      time of the peak VEGF response.

PMID- 14660506
TI  - Higher dietary carbohydrate content during intensified running training results
      in better maintenance of performance and mood state.
AB  - The aim of this study was to determine whether consumption of a diet containing
      8.5 g carbohydrate (CHO) x kg(-1) x day(-1) (high CHO; HCHO) compared with 5.4 g
      CHO x kg(-1) x day(-1) (control; Con) during a period of intensified training
      (IT) would result in better maintenance of physical performance and mood state.
      In a randomized cross-over design, seven trained runners [maximal O(2) uptake
      (Vo(2 max)) 64.7 +/- 2.6 ml x kg(-1) x min(-1)] performed two 11-day trials
      consuming either the Con or the HCHO diet. The last week of both trials consisted
      of IT. Performance was measured with a preloaded 8-km all-out run on the
      treadmill and 16-km all-out runs outdoors. Substrate utilization was measured
      using indirect calorimetry and continuous [U-(13)C]glucose infusion during 30 min
      of running at 58 and 77% Vo(2 max). Time to complete 8 km was negatively affected
      by the IT: time significantly increased by 61 +/- 23 and 155 +/- 38 s in the HCHO
      and Con trials, respectively. The 16-km times were significantly increased (by
      8.2 +/- 2.1%) during the Con trial only. The Daily Analysis of Life Demands of
      Athletes questionnaire showed significant deterioration in mood states in both
      trials, whereas deterioration in global mood scores, as assessed with the Profile
      of Mood States, was more pronounced in the Con trial. Scores for fatigue were
      significantly higher in the Con compared with the HCHO trial. CHO oxidation
      decreased significantly from 1.7 +/- 0.2 to 1.2 +/- 0.2 g/min over the course of
      the Con trial, which was completely accounted for by a decrease in muscle
      glycogen oxidation. These findings indicate that an increase in dietary CHO
      content from 5.4 to 8.5 g CHO x kg(-1)x day(-1) (41 vs. 65% total energy intake,
      respectively) allowed better maintenance of physical performance and mood state
      over the course of training, thereby reducing the symptoms of overreaching.

PMID- 14660507
TI  - The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?
AB  - Mice with allergically inflamed airways are widely used as animal models of
      asthma, but their relevance for human asthma is not understood. We, therefore,
      examined the time course of changes in respiratory input impedance during induced
      bronchoconstriction in BALB/c mice sensitized and challenged with ovalbumin. Our
      results indicate that bronchoconstriction in mice is accompanied by complete
      closure of substantial regions of the lung and that closure increases markedly
      when the lungs are allergically inflamed. With the aid of an anatomically
      accurate computational model of the mouse lung, we show that the
      hyperresponsiveness of mice with allergically inflamed airways can be explained
      entirely by a thickening of the airway mucosa and an increased propensity of the
      airways to close, without the involvement of any increase in the degree of airway
      smooth muscle shortening. This has implications for the pathophysiology of asthma
      and suggests that at least some types of asthma may benefit from therapies aimed
      at manipulating surface tension at the air-liquid interface in the lungs.

PMID- 14660508
TI  - Reproducibility and responsiveness of a noninvasive EMG technique of the
      respiratory muscles in COPD patients and in healthy subjects.
AB  - In the present study, we assessed the reproducibility and responsiveness of
      transcutaneous electromyography (EMG) of the respiratory muscles in patients with
      chronic obstructive pulmonary disease (COPD) and healthy subjects during
      breathing against an inspiratory load. In seven healthy subjects and seven COPD
      patients, EMG signals of the frontal and dorsal diaphragm, intercostal muscles,
      abdominal muscles, and scalene muscles were derived on 2 different days, both
      during breathing at rest and during breathing through an inspiratory threshold
      device of 7, 14, and 21 cm H2O. For analysis, we used the logarithm of the ratio
      of the inspiratory activity during the subsequent loads and the activity at
      baseline [log EMG activity ratio (EMGAR)]. Reproducibility of the EMG was
      assessed by comparing the log EMGAR values measured at test days 1 and 2 in both
      groups. Responsiveness (sensitivity to change) of the EMG was assessed by
      comparing the log EMGAR values of the COPD patients to those of the healthy
      subjects at each load. During days 1 and 2, log EMGAR values of the diaphragm and
      the intercostal muscles correlated significantly. For the scalene muscles,
      significant correlations were found for the COPD patients. Although inspiratory
      muscle activity increased significantly during the subsequent loads in all
      participants, the COPD patients displayed a significantly greater increase in
      intercostal and left scalene muscle activity compared with the healthy subjects.
      In conclusion, the present study showed that the EMG technique is a reproducible
      and sensitive technique to assess breathing patterns in COPD patients and healthy
      subjects.

PMID- 14660509
TI  - Influence of body composition on physical activity validation studies using
      doubly labeled water.
AB  - This study investigated the influence of two approaches (mathematical
      transformation and statistical procedures), used to account for body composition
      [body mass or fat-free mass (FFM)], on associations between two measures of
      physical activity and energy expenditure determined by doubly labeled water
      (DLW). Complete data for these analyses were available for 136 African American
      (44.1%) and Hispanic (55.9%) women (mean age 50 +/- 7.3 yr). Total energy
      expenditure (TEE) by DLW was measured over 14 days. Physical activity energy
      expenditure (PAEE) was computed as 0.90 x TEE - resting metabolic rate. During
      week 2, participants wore an accelerometer for 7 consecutive days and completed a
      7-day diary. Pearson's product-moment correlations and three statistical
      procedures (multiple regressions, partial correlations, and allometric scaling)
      were used to assess the effect of body composition on associations. The methods
      comparison analysis was used to study the effect of body composition on
      agreement. The statistical procedures demonstrated that associations improved
      when body composition was included in the model. The accelerometer explained a
      small but meaningful portion of the variance in TEE and PAEE after body mass was
      accounted for. The methods-comparison analysis confirmed that agreement with DLW
      was affected by the transformation. Agreement between the diary (transformed with
      body mass) and TEE reflected the association that exists between body mass and
      TEE. These results suggest that the accelerometer and diary accounted for a small
      portion of TEE and PAEE. Most of the variance in DLW-measured energy expenditure
      was explained by body mass or FFM.

PMID- 14660510
TI  - Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory
      activity.
AB  - Reflexes arising from the carotid bodies may play an important role in
      cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the
      present study, we examined whether CIH affects the hypoxic sensing ability of the
      carotid bodies and, if so, by what mechanisms. Experiments were performed on
      adult male rats (Sprague-Dawley, 250-300 g) exposed to two paradigms of CIH for
      10 days: 1) multiple exposures to short durations of intermittent hypoxia per day
      (SDIH; 15 s of 5% O(2) + 5 min of 21% O(2), 9 episodes/h, 8 h/day) and 2) single
      exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of
      hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory
      response to graded isocapnic hypoxia was examined in both groups of animals under
      anesthetized conditions. Hypoxic sensory response was significantly enhanced in
      SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was
      also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the
      effects were not secondary to cardiovascular changes. SDIH, however, had no
      significant effect on the hypercapnic sensory response. The effects of SDIH on
      the hypoxic sensory response completely reversed after SDIH animals were placed
      in a normoxic environment for an additional 10 days. Previous treatment with
      systemic administration of O(2)(-)* radical scavenger prevented SDIH-induced
      augmentation of the hypoxic sensory response. These results demonstrate that SDIH
      but not LDIH results in selective augmentation of the hypoxic response of the
      carotid body and O(2)(-)* radicals play an important role in SDIH-induced
      sensitization of the carotid body.

PMID- 14660511
TI  - Red blood cell velocity and oxygen tension measurement in cerebral microvessels
      by double-wavelength photoexcitation.
AB  - Because the regulation of microcirculation in the cerebral cortex cannot be
      analyzed without measuring the blood flow dynamics and oxygen concentration in
      cerebral microvessels, we developed a fluorescence and phosphorescence system for
      estimating red blood cell velocity and oxygen tension in cerebral
      microcirculation noninvasively and continuously with high spatial resolution.
      Using red blood cells labeled with fluorescent isothiocyanate to visualize red
      cell distribution and using the oxygen quenching of Pd-meso-tetra-(4
      carboxyphenyl)-porphyrin phosphorescence to measure oxygen tension enabled
      simultaneous measurement of blood velocity and oxygen tension. We examined how
      the measurement accuracy was affected by the spatial resolution and by the
      excitation laser light passing through the targeted microvessel and exciting the
      oxygen probe dye in the tissue beneath it. Focusing the excitation light into the
      microvessel stabilized the phosphorescence lifetime at each spatial resolution;
      moreover, it greatly reduced phosphorescence from the brain tissue. Animal
      experiments involving acute hemorrhagic shock demonstrated the feasibility of our
      system by showing that the changes in venular velocity and oxygen tension are
      synchronized to the change in mean arterial pressure. Our system measures the red
      cell velocity and oxygen concentration in the cerebral microcirculation by using
      the differences in luminescence and wavelength between fluorescence and
      phosphorescence, making it possible to easily acquire information about cerebral
      microcirculatory distribution and oxygen tension simultaneously.

PMID- 14660512
TI  - Intramuscular pressure and EMG relate during static contractions but dissociate
      with movement and fatigue.
AB  - Intramuscular pressure (IMP) and electromyography (EMG) mirror muscle force in
      the nonfatigued muscle during static contractions. The present study explores
      whether the constant IMP-EMG relationship with increased force may be extended to
      dynamic contractions and to fatigued muscle. IMP and EMG were recorded from
      shoulder muscles in three sessions: 1). brief static arm abductions at angles
      from 0 to 90 degrees, with and without 1 kg in the hands; 2). dynamic arm
      abductions at angular velocities from 9 to 90 degrees /s, with and without 1 kg
      in the hands; and 3). prolonged static arm abduction at 30 degrees for 30 min
      followed by recovery. IMP and EMG increased in parallel with increasing shoulder
      torque during brief static tasks. During dynamic contractions, peak IMP and EMG
      increased to values higher than those during static contractions, and EMG, but
      not IMP, increased significantly with speed of abduction. In the nonfatigued
      supraspinatus muscle, a linear relationship was found between IMP and EMG; in
      contrast, during fatigue and recovery, significant timewise changes of the IMP-to
      EMG ratio occurred. The results indicate that IMP should be included along with
      EMG when mechanical load sharing between muscles is evaluated during dynamic and
      fatiguing contractions.

PMID- 14660513
TI  - Diurnal variation of aldosterone and plasma renin activity: timing relation to
      melatonin and cortisol and consistency after prolonged bed rest.
AB  - Exposure to prolonged bed rest is known to induce changes in the renin
      angiotensin-aldosterone system (RAAS) by way of posture, sodium and potassium
      balance, and stress, which may have serious consequences for patients. We focused
      on the diurnal variation of the RAAS by investigating changes in the levels of
      plasma renin activity (PRA) and aldosterone; for comparison to markers of the
      intrinsic pacemaker and to stress, we measured melatonin and cortisol. PRA,
      aldosterone, melatonin, and cortisol were measured hourly in 10 normal subjects
      with standardized sleep patterns, posture, and diet at baseline and after 11 days
      of prolonged bed rest conducted under a light-dark cycle. Circadian
      characteristics of hormone secretion patterns were estimated by multiple harmonic
      regression with excellent goodness-of-fit measures. Variability in the melatonin
      and cortisol patterns across subjects was minimal. Even for pulsatile hormones,
      this technique successfully estimated the acrophase, which was the salient
      feature. Baseline hormone peak times started with melatonin near the middle of
      the sleep period, followed by PRA, then aldosterone, and then cortisol around
      wake time. Prolonged bed rest did not induce significant changes in any timing
      characteristic of the secretion patterns. Baseline and prolonged bed rest peak
      times for melatonin and cortisol and amplitude characteristics for all hormones
      were highly correlated, indicating consistency within individuals. These data
      provide strong evidence that prolonged bed rest of 11 days' duration does not
      disrupt either the timing characteristics of the RAAS or the intrinsic pacemaker.

PMID- 14660514
TI  - Hypercapnia increases core temperature cooling rate during snow burial.
AB  - Previous retrospective studies report a core body temperature cooling rate of 3
      degrees C/h during avalanche burial. Hypercapnia occurs during avalanche burial
      secondary to rebreathing expired air, and the effect of hypercapnia on
      hypothermia during avalanche burial is unknown. The objective of this study was
      to determine the core temperature cooling rate during snow burial under
      normocapnic and hypercapnic conditions. We measured rectal core body temperature
      (T(re)) in 12 subjects buried in compacted snow dressed in a lightweight clothing
      insulation system during two different study burials. In one burial, subjects
      breathed with a device (AvaLung 2, Black Diamond Equipment) that resulted in
      hypercapnia over 30-60 min. In a control burial, subjects were buried under
      identical conditions with a modified breathing device that maintained
      normocapnia. Mean snow temperature was -2.5 +/- 2.0 degrees C. Burial time was 49
      +/- 14 min in the hypercapnic study and 60 min in the normocapnic study (P =
      0.02). Rate of decrease in T(re) was greater with hypercapnia (1.2 degrees C/h by
      multiple regression analysis, 95% confidence limits of 1.1-1.3 degrees C/h) than
      with normocapnia (0.7 degrees C/h, 95% confidence limit of 0.6-0.8 degrees C/h).
      In the hypercapnic study, the fraction of inspired carbon dioxide increased from
      1.4 +/- 1.0 to 7.0 +/- 1.4%, minute ventilation increased from 15 +/- 7 to 40 +/-
      12 l/min, and oxygen saturation decreased from 97 +/- 1 to 90 +/- 6% (P < 0.01).
      During the normocapnic study, these parameters remained unchanged. In this study,
      T(re) cooling rate during snow burial was less than previously reported and was
      increased by hypercapnia. This may have important implications for prehospital
      treatment of avalanche burial victims.

PMID- 14660515
TI  - Carbon dioxide added late in inspiration reduces ventilation-perfusion
      heterogeneity without causing respiratory acidosis.
AB  - We have shown previously that inspired CO2 (3-5%) improves ventilation-perfusion
      (Va/Q) matching but with the consequence of mild arterial hypercapnia and
      respiratory acidosis. We hypothesized that adding CO2 only late in inspiration to
      limit its effects to the conducting airways would enhance Va/Q matching and
      improve oxygenation without arterial hypercapnia. CO2 was added in the latter
      half of inspiration in a volume aimed to reach a concentration of 5% in the
      conducting airways throughout the respiratory cycle. Ten mixed-breed dogs were
      anesthetized and, in a randomized order, ventilated with room air, 5% CO2
      throughout inspiration, and CO2 added only to the latter half of inspiration. The
      multiple inert-gas elimination technique was used to assess Va/Q heterogeneity.
      Late-inspired CO2 produced only very small changes in arterial pH (7.38 vs. 7.40)
      and arterial CO2 (40.6 vs. 39.4 Torr). Compared with baseline, late-inspired CO2
      significantly improved arterial oxygenation (97.5 vs. 94.2 Torr), decreased the
      alveolar-arterial Po2 difference (10.4 vs. 15.7 Torr) and decreased the multiple
      inert-gas elimination technique-derived arterial-alveolar inert gas area
      difference, a global measurement of Va/Q heterogeneity (0.36 vs. 0.22). These
      changes were equal to those with 5% CO2 throughout inspiration (arterial Po2,
      102.5 Torr; alveolar-arterial Po2 difference, 10.1 Torr; and arterial-alveolar
      inert gas area difference, 0.21). In conclusion, we have established that the
      majority of the improvement in gas exchange efficiency with inspired CO2 can be
      achieved by limiting its application to the conducting airways and does not
      require systemic acidosis.

PMID- 14660517
TI  - ISQua's 4th International Summit on Indicators, Buenos Aires, October 2001.

PMID- 14660518
TI  - Developing evidence-based clinical indicators: a state of the art methods primer.
AB  - OBJECTIVE: To describe steps in developing and testing clinical indicators based
      on state of the art methods in previous literature and experience in the Danish
      National Indicator Project. ANALYSIS: The development process includes a planning
      phase, where the clinical area to be evaluated is chosen and the measurement team
      selected and organized. The planning phase is followed by a development phase
      where clinical indicators are prioritized and selected by the measurement team on
      the basis of documentation and knowledge from the scientific literature. When
      clinical indicators have been selected, specific measure specifications should be
      designed, including inclusion and exclusion criteria for the target population,
      description of a risk adjustment strategy, identification of data sources,
      description of data collection procedures, and an analytical plan for data
      analyses. Before clinical indicators are implemented they should be tested for
      reliability and validity. Preliminary tests may identify areas requiring further
      modifications and specifications of the indicators. CONCLUSION: Using clinical
      indicators for quality assessment represents an important approach to documenting
      the quality of care. Consumers of indicator information (clinicians,
      administrators, purchasers, regulators, and patients) need reliable and valid
      information for benchmarking, making judgments, and determining priorities,
      accountability and quality improvement. This underlines the fact that clinical
      indicators must be developed and tested with scientific rigor in a transparent
      process.

PMID- 14660519
TI  - Indicators to improve clinical quality across an integrated health care system.
AB  - PURPOSE: To describe key historical and operational elements of change that may
      assist an organization to develop quality indicators for implementing a strategic
      plan to improve care, align health care improvement efforts with national
      directions, and examine the types of medication indicators used to assess these
      changes. SETTING: The Baylor Health Care System (BHCS) is an integrated health
      care delivery organization in Dallas-Fort Worth, Texas. It includes 11 hospitals
      with 83 000 admissions per year and 47 primary care and senior centers with more
      than 500 000 visits annually. INTERVENTION: Following a charter by the BHCS Board
      of Trustees to develop a health care quality improvement strategic plan, BHCS
      undertook a system-wide effort to improve care supported by the use of clinical
      quality indicators. RESULTS: Consistent with the direction of the US Institute of
      Medicine, BHCS has implemented a clinical indicator system focused on measures of
      health care underuse, overuse, and misuse. These indicators demonstrated the
      accomplishments of specific process of care improvements throughout BHCS. Despite
      implementing Web-enabled error reporting systems and pilot work with an adverse
      drug event hospital medical record abstraction tool, BHCS indicators of
      medication misuse continue to be in a formative stage, much like the national
      consensus. CONCLUSION: Organizational, compensatory, and cultural commitments may
      be important for successful implementation of clinical indicator initiatives by
      health care systems. Using clinical indicators to establish baseline performance
      and to assess the effectiveness of proposed quality improvements provides
      quantitative and qualitative means to identify and disseminate best care
      practices. Although indicators to measure underuse of clinically necessary care
      are well established, there remains a need to achieve consensus regarding
      practicable medication quality indicators for overuse, misuse, and adverse drug
      events.

PMID- 14660520
TI  - The US Agency for Healthcare Research and Quality's activities in patient safety
      research.
AB  - PURPOSE: To update the international community on the US Agency for Healthcare
      Research and Quality's (AHRQ) recent and current activities in improving patient
      safety. DATA SOURCES: Review of the literature concerning the importance of
      patient safety as a health care quality issue, international perspectives on
      patient safety, a review of research solicitations, and early results of funded
      studies. STUDY SELECTION: A representative sample of patient safety studies from
      those currently being funded by AHRQ. RESULTS: In response to a growing interest
      in patient safety in general and a recent US Institute of Medicine report on
      patient safety in particular, the US Agency for Healthcare Research and Quality
      has refocused its quality research mission. In the fiscal year 2002, AHRQ spent
      US$55 million on patient safety research. This investment was spread across six
      complementary research areas: (1) health systems error reporting, analysis, and
      safety improvement research demonstrations; (2) Clinical Informatics to Promote
      Patient Safety (CLIPS); (3) Centers of Excellence for patient safety research and
      practice (COE); (4) Developmental Centers for Evaluation and Research in Patient
      Safety (DCERPS); (5) The Effect of Health Care Working Conditions on Quality of
      Care; and (6) Partnerships for Quality: Patient Safety Research Dissemination and
      Education. Internal teams of researchers at AHRQ have published studies on
      patient safety, such as documenting the impact of medication errors. In addition
      to funding research on patient safety, AHRQ is an integral partner in several
      national and international collaborations to form strategic synergies that build
      upon each member organization's strengths, reduce redundant efforts, and benefit
      from each other's successes. As evidence on patient safety is generated, AHRQ
      also serves the important mission of disseminating information to the public.
      CONCLUSION: The patient safety research field has undergone a period of rapid
      evolution. It is now incumbent upon the international health care quality
      improvement community to translate the future results of this research investment
      into improved safety for patients.

PMID- 14660521
TI  - Improving patient safety across a large integrated health care delivery system.
AB  - OBJECTIVE: Patient safety is moving up the list of priorities for hospitals and
      health care delivery systems, but improving safety across a large organization is
      challenging. We sought to create a common patient safety strategy for the
      Partners HealthCare system, a large, integrated, non-profit health care delivery
      system in the United States. DESIGN: Partners identified a central Patient Safety
      Officer, who then formed a Patient Safety Advisory Group with local expert
      members, as well as a Patient Safety Leaders Group comprised of personnel
      responsible for patient safety at each member institution. The latter group meets
      monthly to help determine future projects and to share the results of piloting
      and implementation. There was broad consensus that interventions should include
      the areas of culture change, process change, and process measurement. SETTING: A
      large, integrated health care delivery system in the Boston, Massachusetts, area.
      RESULTS: Key milestones to date include implementation of Executive WalkRounds,
      development of accountability principles, agreement to create a common system
      wide adverse event reporting system, and agreement to implement computerized
      physician order entry in all hospitals. These efforts have heightened awareness
      of patient safety considerably within the network. Most influenced to date have
      been the senior leaders of the hospitals, which has resulted in substantial
      support for patient safety initiatives. CONCLUSIONS: This loosely integrated
      delivery system represents a daunting landscape for the development and
      institution of patient safety concepts. Many projects aimed at different
      components of patient safety must occur at the same time for significant change,
      yet culture and care-related beliefs vary substantially within the system, and
      measurement is especially challenging. Moreover, with many potential
      interventions, and limited resources, prioritization and selection is difficult.
      Nonetheless, consensus about some issues has been reached, in particular because
      of a well delineated patient safety structure. We believe the net result will be
      substantial improvement in patient safety.

PMID- 14660522
TI  - Improving medication safety: the measurement conundrum and where to start.
AB  - The use of medication remains the most common intervention in health care. The
      complexity of both medication use and the medication management process,
      especially in the in-patient setting, create a significant risk for hospitalized
      patients. Despite the widespread recognition of the hazards that medication use
      poses to patients, there are no widely accepted or standardized methods to
      measure the safety of medication use. Where to focus measurement in medication
      safety is the subject of ongoing debate. Various groups have suggested measuring
      error-prone aspects of the medication use process such as errors in
      administration of medications or errors in dispensing of medications. Other
      groups have suggested measuring adverse drug events as a measure of the safety of
      medication use. Many studies in this area have outlined the great difficulty
      associated with getting clinicians to report either medication errors or adverse
      drug events voluntarily. In response to these challenges, yet more groups have
      developed non-voluntary reporting methods based on the use of "triggers", in
      either a chart review or electronic format. Medication safety is a complex
      process and measurement of it needs to be a core component throughout the whole
      process. With the introduction of computerized analysis of patient information,
      measurement becomes much easier and potentially more powerful and achievable than
      either incident reporting or chart reviews for purposes of accountability,
      prevention, and ongoing improvement of both process and clinical practice. This
      paper reviews approaches to measuring medication safety from the perspective of
      both harm and error, and outlines a strategy that combines both approaches in the
      electronic era.

PMID- 14660523
TI  - Adverse drug events and medication errors in Australia.
AB  - PURPOSE: To review information about adverse drug events (ADEs) and medication
      errors in Australia. DATA SOURCES: Systematic literature reviews and reports from
      data collections of the Australian Bureau of Statistics, Institute of Health and
      Welfare, Council for Health Care Standards and Patient Safety Foundation.
      RESULTS: (medical record reviews): We have shown that 2-4% of all hospital
      admissions, and up to 30% for patients > 75 years of age, are medication-related;
      up to three-quarters are potentially preventable. RESULTS (routine data
      collections): Routine death certificate and hospital discharge data coded using
      the International Classification of Diseases capture less than half as many ADEs
      as medical record reviews. Of coded adverse events that contributed to death, 27%
      involved an ADE, as did 20% of adverse events identified at discharge and 43% at
      general practice encounters. There is a strong correlation between increases in
      medication use and rates of adverse drug reactions (ADRs) associated with
      hospitalization. RESULTS (drugs implicated): These were similar in all the above
      studies: anticoagulants, anti-inflammatory drugs, opioids, anti-neoplastics,
      antihypertensives, antibiotics, cardiac glycosides, diuretics, hypoglycaemic
      agents, steroids, hypnotics, anticonvulsants, and antipsychotics. RESULTS
      (clinical indicators): An ADE is reported in 1% of hospital admissions, while
      some hospitals do not report ADRs to the national collection. Only three-quarters
      of patients with acute myocardial infarction receive thrombolytics within 1 hour
      of presentation. Five per cent of patients on warfarin record an international
      normalized ratio > 5, and 1%, 0.05%, and 0.2% -suffer abnormal bleeding, cerebral
      haemorrhage, or death, respectively. RESULTS (the Australian Incident Monitoring
      System): Twenty-six per cent of 27 000 hospital-related incidents were medication
      related, as were 36% of 2000 anaesthesia-related incidents, and 50% of 2500
      general practice incidents. RESULTS (errors): Errors occur in 15-20% of drug
      administrations when ward stock systems are used and 5-8% when individual patient
      systems are used. Previous allergic reactions to drugs may not be recorded more
      than 75% of the time. CONCLUSION: ADEs are common in the Australian health
      system. Anticoagulant, anti-inflammatory, and cardiovascular drugs feature
      prominently as preventable, high impact problems, and collectively make up over
      one-half of all ADEs. Methods for monitoring and preventing ADEs should be
      progressively improved.

PMID- 14660527
TI  - Evaluating accreditation.

PMID- 14660528
TI  - Improving quality: bridging the health sector divide.
AB  - ISSUE: All too often, quality assurance looks at just one small part of the
      complex system that is health care. However, evidently each individual patient
      has one set of experiences and outcomes, often involving a range of health
      professionals in a number of settings across multiple sectors. ADDRESSING THE
      ISSUE: In order to solve the problems of this complexity, we need to establish
      high-quality electronic recording in each of the settings. In the UK, primary
      care has been leading the way in adopting information technology and can now use
      databases for individual clinical care, for quality assurance using significant
      event and conventional auditing, and for research. BUILDING TOWARDS A SOLUTION:
      Before we can understand and quality-assure the whole health care system, we need
      electronic patient records in all settings and good communication to build a
      summary electronic health record for each patient. Such an electronic health
      record will be under the control of the patient concerned, will be shared with
      the explicit consent of the patient, and will form the vehicle for quality
      assurance across all sectors of the health service.

PMID- 14660529
TI  - Results of the first 100 accreditation procedures in France.
AB  - PURPOSE: To identify the areas of needed improvement that were most frequently
      identified in the first 100 accredited hospitals by the French Accreditation
      College (FAC) according to the standards manual. To compare the outcomes of
      accreditation procedures according to the status and size of the accredited
      hospitals. DATA SOURCES: We analyzed the first 100 summaries of accreditation
      reports available on the website of the Agence Nationale d'Accreditation et
      d'Evaluation en Sante (ANAES). DATA EXTRACTION: Data were collected on hospitals,
      accreditation processes, and outcomes (decisions of the FAC). For each decision,
      we assessed the relationship with accreditation manual criteria, and analyzed
      their distribution by chapter. RESULTS: of data synthesis. Among the 100
      accredited hospitals (40 public, 43 private, 17 mixed), nine were accredited
      without recommendations for improvement, 47 with recommendations, 40 with
      reservations, and four with major reservations. All of them received requests for
      improvement. No significant difference was found concerning the FAC decisions
      according to status and size of hospitals, although there was a trend that the
      larger the hospital, the more numerous and more serious the decisions of the FAC.
      The main topics addressed by decisions were those given high priority by the FAC
      (information given to patients and its traceability on patient records, and
      signing of prescriptions for medication). CONCLUSION: Despite wide heterogeneity
      in the summaries on accreditation and in FAC decision-making, this study provides
      an initial insight into common quality defects and ANAES priorities for hospitals
      in France.

PMID- 14660530
TI  - 'Emerge': Benchmarking of clinical performance and patients' experiences with
      emergency care in Switzerland.
AB  - OBJECTIVE: To assess the effects of uniform indicator measurement and group
      benchmarking followed by hospital-specific activities on clinical performance
      measures and patients' experiences with emergency care in Switzerland. DESIGN:
      Data were collected in a pre-post design in two measurement cycles, before and
      after implementation of improvement activities. Trained hospital staff recorded
      patient characteristics and clinical performance data. Patients completed a
      questionnaire after discharge/transfer from the emergency unit. SETTING:
      Emergency departments of 12 community hospitals in Switzerland, participating in
      the 'Emerge' project. SUBJECTS: Eligible patients were entered into the study (18
      544 in total: 9174 and 9370 in the first and second cycles, respectively), and
      2916 and 3370 patients returned the questionnaire in the first and second
      measurement cycles, respectively (response rates 32% and 36%, respectively). MAIN
      OUTCOME MEASURES: Clinical performance measures (concordance of prospective and
      retrospective assessment of urgency of care needs, and time intervals between
      sequences of events) and patients' reports about care provision in emergency
      departments (EDs), measured by a 22-item, self-administered questionnaire.
      RESULTS: Concordance of prospective and retrospective assignments to one of three
      urgency categories improved significantly by 1%, and both under- and over
      prioritization, were reduced. The median duration between ED admission and
      documentation of post-ED disposition fell from 137 minutes in 2001 to 130 minutes
      in 2002 (P < 0.001). Significant improvements in the reports provided by patients
      were achieved in 10 items, and were mainly demonstrated in structures of care
      provision and perceived humanity. CONCLUSION: Undertaken in a real-world setting,
      small but significant improvements in performance measures and patients'
      perceptions of emergency care could be achieved. Hospitals accomplished these
      improvements mainly by averting strong outliers, and were most successful in
      preventing series of negative events. Uniform outcomes measurement, group
      benchmarking, and data-driven hospital-specific strategies for change are
      suggested as valuable tools for continuous improvement. Several hospitals have
      already implemented the developed measures in their internal quality systems and
      subsequent measurements are projected.

PMID- 14660531
TI  - Validity and reliability of guidelines for neck pain treatment in primary health
      care. A nationwide empirical analysis in Spain.
AB  - OBJECTIVES: To assess the reliability and validity of existing clinical
      guidelines on neck-pain physiotherapy treatment and follow-up in Spain. DESIGN:
      We identified existing guidelines through a nationwide census and listed their
      recommendations, grouped according to the main steps of the process flow-chart.
      To assess reliability we analysed the variability of statements. To analyse
      validity we assessed the type of scientific evidence supporting the
      recommendations, and we compared them with a list of evidence-based
      recommendations that was elaborated for this study. SETTING AND PARTICIPANTS:
      Primary health care centres (n = 24) with guidelines for neck-pain treatment and
      follow-up. MAIN OUTCOME MEASURES: We quantified the number of recommendations,
      the proportion of valid statements, the frequencies of non-evidence-based
      recommendations, and the absence of the evidence-based recommendations we had
      identified. RESULTS: The 34 identified guidelines contained 325 recommendations,
      with great variation between guidelines with respect to the number, type (for up
      to 26 different clinical decisions), and content of the recommendations they
      provided. Direct assessment of the scientific evidence was not possible because
      no specific reference was given to support any recommendation. When compared with
      our list, only 20.9% of the recommendations could be considered evidence-based.
      No guideline contained all the eight evidence-based recommendations we
      identified. CONCLUSIONS: The results question the guidelines' reliability and
      validity, and their usefulness in ensuring quality. We conclude that guidelines
      should be reviewed and re-designed with greater scientific rigour.

PMID- 14660532
TI  - Soup kitchen consumer perspectives on the quality and frequency of health service
      interactions.
AB  - OBJECTIVE: Whilst previous research has repeatedly documented premature mortality
      and high morbidity among seriously disadvantaged and homeless populations, far
      less is known of the extent and nature of their interactions with health
      services. DESIGN AND SETTING: This cross-sectional case study describes health
      service utilization patterns and explores participant-reported difficulties in
      accessing health care, adhering to prescribed treatment and maintaining
      continuity of care amongst 100 users of a charity-run soup kitchen in urban
      Sydney. Participants and results. The study describes a largely welfare-dependent
      population sample with poor health who are frequent users of the health system
      (85% had seen a general practitioner in the preceding 6 months). The homeless
      were more likely to report difficulties accessing health care when needed [odds
      ratio 3.15; 95% confidence interval (CI) 1.04-9.62]. One in three respondents
      reported difficulty adhering to prescribed treatment following their last health
      care visit. Affordability (P < 0.0001), not understanding instructions (P =
      0.007), and not agreeing with advice (P < 0.0001) were the main factors
      associated with adherence difficulties. One in four failed to return for follow
      up visits as advised, largely associated with attitudinal barriers such as a
      history of not believing problems would be addressed (P = 0.05), not trusting
      health professionals (P = 0.04), and not knowing where to get help in the past (P
      = 0.05). CONCLUSION: These results reinforce the important role of free primary
      care in reducing access barriers for the disadvantaged, but also highlight
      possible reasons for service interactions being ineffective in a substantial
      proportion of cases.

PMID- 14660533
TI  - User satisfaction with a real-time automated feedback system for general
      practitioners: a quantitative and qualitative study.
AB  - OBJECTIVE: The GRIF automated feedback system produces real-time comments on the
      appropriateness of diagnostic tests ordered by general practitioners (GPs) based
      on recommendations from accepted national and regional practice guidelines. We
      investigated the experiences of GPs with this system and, more specifically, with
      the recommendations produced by the system as well as their views on using this
      system in daily practice. SETTING: We tested the GRIF system in an experiment in
      a laboratory setting and in a daily practice trial. STUDY PARTICIPANTS: General
      practitioners. INTERVENTION: In the laboratory experiment, GPs used the GRIF
      system to assess the appropriateness of 30 request forms. Each of the GPs was
      confronted with requests they had submitted to the diagnostic unit of the
      hospital in the past. In the field trial, the GRIF system was applied during
      patient consultations for 1 year. MAIN OUTCOME MEASURES: We measured GPs'
      satisfaction with the system using a questionnaire, and also conducted group
      discussions (in the laboratory experiment) and in-depth interviews (in the field
      trial) to elicit GPs' opinions of and experiences with the system. In addition,
      we explored GPs' reasons for not accepting the comments offered by the GRIF
      system. RESULTS: The results show that the GPs in the laboratory experiment had
      more positive attitudes towards the system compared with participants in the
      field trial. All discussion groups and most of the GPs in the field trial
      regarded receiving the immediate feedback during the test ordering process as an
      important advantage. The most frequently mentioned reason to reject the
      recommendation was disagreement with the content and/or the recommendations in
      the practice guidelines. CONCLUSION: Apart from securing agreement on guideline
      content, a prerequisite for using GRIF in daily practice on a large scale is that
      more attention is paid to promotion of the guidelines and their adoption, and
      stimulation of a positive attitude towards the practice guidelines among the
      users.

PMID- 14660534
TI  - Reducing clinical variations with clinical pathways: do pathways work?
AB  - OBJECTIVE: To test clinical pathways in a variety of Italian health care
      organizations in 2000-2002 to measure performance in decreasing process and
      outcome variations. DESIGN: Creation of indicators, specific for each clinical
      pathway, to measure variations in the care processes and outcomes. Pre- and post
      analysis model to evaluate the possible effect of the clinical pathways on each
      indicator. SETTING: We tested the clinical pathways in six sites, each with
      different clinical pathways. RESULTS: Reductions in health care macro-variation
      phenomena (length of stay, patient pathways, etc.) and in performance micro
      variation (variations in diagnostic and therapeutic prescriptions, protocol
      implementation, etc.) were shown in sites where pathways were implemented
      successfully. A significant improvement in outcome for patients who were treated
      according to the clinical pathway for heart failure was also demonstrated.
      CONCLUSIONS: The overall purpose of clinical pathways is to improve outcome by
      providing a mechanism to coordinate care and to reduce fragmentation, and
      ultimately cost. Our results demonstrated that it is possible to achieve this
      goal. Although controversial elements still exist, we think that clinical
      pathways can have a positive impact on quality in health care.

PMID- 14660535
TI  - Defining and classifying clinical indicators for quality improvement.
AB  - OBJECTIVE: This paper provides a brief review of definitions, characteristics,
      and categories of clinical indicators for quality improvement in health care.
      ANALYSIS: Clinical indicators assess particular health structures, processes, and
      outcomes. They can be rate- or mean-based, providing a quantitative basis for
      quality improvement, or sentinel, identifying incidents of care that trigger
      further investigation. They can assess aspects of the structure, process, or
      outcome of health care. Furthermore, indicators can be generic measures that are
      relevant for most patients or disease-specific, expressing the quality of care
      for patients with specific diagnoses. CONCLUSIONS: Monitoring health care quality
      is impossible without the use of clinical indicators. They create the basis for
      quality improvement and prioritization in the health care system. To ensure that
      reliable and valid clinical indicators are used, they must be designed, defined,
      and implemented with scientific rigour.

PMID- 14660539
TI  - Finger or toe: the molecular basis of limb identity.
AB  - Despite their obvious similarities, the forelimbs and hindlimbs of tetrapod
      vertebrates have evolved distinct structural elements to carry out their discrete
      functions. Many genes required for limb initiation and patterning are involved in
      regulatory networks common to both limb-types. Other genes are differentially
      expressed between forelimb and hindlimb, and have been implicated in the
      initiation of limb bud outgrowth and the specification of limb-type identity. In
      this review, I will discuss the current understanding of how genes that control
      limb identity interact with regulatory networks common to both appendages to
      produce the fingers of the hand and toes of the foot.

PMID- 14660540
TI  - Wg and Egfr signalling antagonise the development of the peripodial epithelium in
      Drosophila wing discs.
AB  - Imaginal discs contain a population of cells, known as peripodial epithelium,
      that differ morphologically and genetically from the rest of imaginal cells. The
      peripodial epithelium has a small contribution to the adult epidermis, though it
      is essential for the eversion of the discs during metamorphosis. The genetic
      mechanisms that control the identity and cellular morphology of the peripodial
      epithelia are poorly understood. In this report, we investigate the mechanisms
      that pattern the peripodial side of the wing imaginal disc during early larval
      development. At this time, the activities of the Wingless (Wg) and Epidermal
      growth factor receptor (Egfr) signalling pathways specify the prospective wing
      and notum fields, respectively. We show that peripodial epithelium specification
      occurs in the absence of Wingless and Egfr signalling. The ectopic activity in
      the peripodial epithelium of any of these signalling pathways transforms the
      shape of peripodial cells from squamous to columnar and resets their gene
      expression profile. Furthermore, peripodial cells where Wingless signalling is
      ectopically active acquire hinge identity, while ectopic Egfr activation results
      in notum specification. These findings suggest that suppression of Wg and Egfr
      activities is an early step in the development of the peripodial epithelium of
      the wing discs.

PMID- 14660541
TI  - Recruitment of C. elegans dosage compensation proteins for gene-specific versus
      chromosome-wide repression.
AB  - In C. elegans, an X-chromosome-wide regulatory process compensates for the
      difference in X-linked gene dose between males (XO) and hermaphrodites (XX) by
      equalizing levels of X-chromosome transcripts between the sexes. To achieve
      dosage compensation, a large protein complex is targeted to the X chromosomes of
      hermaphrodites to reduce their expression by half. This repression complex is
      also targeted to a single autosomal gene, her-1. By silencing this male-specific
      gene, the complex induces hermaphrodite sexual development. Our analysis of the
      atypical dosage compensation gene dpy-21 revealed the first molecular differences
      in the complex that achieves gene-specific versus chromosome-wide repression. dpy
      21 mutations, shown here to be null, cause elevated X-linked gene expression in
      XX animals, but unlike mutations in other dosage compensation genes, they do not
      cause extensive XX-specific lethality or disrupt the stability or targeting of
      the dosage compensation complex to X. Nonetheless, DPY-21 is a member of the
      dosage compensation complex and localizes to X chromosomes in a hermaphrodite
      specific manner. However, DPY-21 is the first member of the dosage compensation
      complex that does not also associate with her-1. In addition to a difference in
      the composition of the complex at her-1 versus X, we also found differences in
      the targeting of the complex to these sites. Within the complex, SDC-2 plays the
      lead role in recognizing X-chromosome targets, while SDC-3 plays the lead in
      recognizing her-1 targets.

PMID- 14660542
TI  - Wingless and Notch signaling provide cell survival cues and control cell
      proliferation during wing development.
AB  - Tissue growth during animal development depends on the coordination of cell
      proliferation and cell death. The EGF-receptor/MAPK, Hedgehog, Dpp, Wingless (Wg)
      and Notch signaling pathways have been implicated in growth control in the
      developing Drosophila wing. In this report, we examine the effects of Notch and
      Wg on growth in terms of cell proliferation and cell survival. Reduction of Wg
      signaling impaired compartment and clonal growth, and increased cell death.
      Inhibition of apoptosis in cells deficient for Wg signaling only partially
      rescued the clone growth defect, suggesting that Wg is also required to promote
      cell proliferation. This is supported by the finding that ectopic expression of
      Wg caused over-proliferation of cells in the proximal wing. Localized activation
      of Notch had non-autonomous effects on cell proliferation. However, only part of
      this effect was attributable to Notch-dependent induction of Wg, suggesting that
      other Notch-inducible signaling molecules contribute to the control of cell
      proliferation in the wing.

PMID- 14660543
TI  - Mitf expression is sufficient to direct differentiation of medaka blastula
      derived stem cells to melanocytes.
AB  - Embryonic stem (ES) cell lines have provided very useful models to analyse
      differentiation processes. We present here the development of a differentiation
      system using ES-like cell lines from medaka. These cells were transfected with
      the melanocyte specific isoform of the microphtalmia-related transcription factor
      (Mitf). Mitf is a basic helix-loop-helix-leucine zipper transcription factor
      whose M isoform is restricted to neural crest derived melanocytes and is
      essential for the development of these cells in vertebrates from mammals to fish.
      What is not clear yet is whether Mitf is a downstream factor or a master
      regulator of melanocyte commitment and differentiation. Expression of Mitf in the
      ES-like cells from medaka led to the induction of cells that, by morphology,
      physiology and gene expression pattern, were confirmed to be fully differentiated
      pigment cells. Mitf expression is therefore sufficient for the proper
      differentiation of medaka pluripotent stem cells into melanocytes.

PMID- 14660544
TI  - Retinoic acid regulates a subset of Cdx1 function in vivo.
AB  - Hox gene products are key players in establishing positional identity along the
      anteroposterior (AP) axis. In vertebrates, gain or loss of Hox expression along
      the AP axis often leads to inappropriate morphogenesis, typically manifesting as
      homeotic transformations that affect the vertebrae and/or hindbrain. Various
      signalling pathways are known to impact on Hox expression, including the retinoid
      signalling pathway. Exogenous retinoic acid (RA), disruption of enzymes involved
      in maintaining normal embryonic RA distribution or mutation of the retinoid
      receptors (RARs and RXRs) can all impact on Hox expression with concomitant
      effects on AP patterning. Several Hox loci have well characterized RA response
      elements (RAREs), which have been shown to regulate functionally relevant Hox
      expression in the neurectoderm. A similar crucial function for any RARE in
      mesodermal Hox expression has, however, not been documented. The means by which
      RA regulates mesodermal Hox expression could therefore be either through an
      undocumented direct mechanism or through an intermediary; these mechanisms are
      not necessarily exclusive. In this regard, we have found that Cdx1 may serve as
      such an intermediary. Cdx1 encodes a homeobox transcription factor that is
      crucial for normal somitic expression of several Hox genes, and is regulated by
      retinoid signalling in vivo and in vitro likely through an atypical RARE in the
      proximal promoter. In order to more fully understand the relationship between
      retinoid signalling, Cdx1 expression and AP patterning, we have derived mice in
      which the RARE has been functionally inactivated. These RARE-null mutants exhibit
      reduced expression of Cdx1 at all stages examined, vertebral homeotic
      transformations and altered Hox gene expression which correlates with certain of
      the defects seen in Cdx1-null offspring. These findings are consistent with a
      pivotal role for retinoid signalling in governing a subset of expression of Cdx1
      crucial for normal vertebral patterning.

PMID- 14660545
TI  - Information display by transcriptional enhancers.
AB  - Transcriptional enhancers integrate positional and temporal information to
      regulate the complex expression of developmentally controlled genes. Current
      models suggest that enhancers act as computational devices, receiving multiple
      inputs from activators and repressors and resolving them into a single positive
      or a negative signal that is transmitted to the basal transcriptional machinery.
      We show that a simple, compact enhancer is capable of representing both repressed
      and activated states at the same time and in the same nucleus. This finding
      suggests that closely apposed factor binding sites, situated within compact cis
      elements, can be independently interpreted by the transcriptional machinery,
      possibly through successive enhancer-promoter interactions. These results provide
      clear evidence that the computational functions usually ascribed to the enhancer
      itself are actually shared with the basal machinery. In contrast to the
      autonomous computer model of enhancer function, an information-display or
      'billboard' model of enhancer activity may better describe many developmentally
      regulated transcriptional enhancers.

PMID- 14660546
TI  - VARICOSE, a WD-domain protein, is required for leaf blade development.
AB  - To gain insight into the processes controlling leaf development, we characterized
      an Arabidopsis mutant, varicose (vcs), with leaf and shoot apical meristem
      defects. The vcs phenotype is temperature dependent; low temperature growth
      largely suppressed defects, whereas high growth temperatures resulted in severe
      leaf and meristem defects. VCS encodes a putative WD-domain containing protein,
      suggesting a function involving protein-protein interactions. Temperature shift
      experiments indicated that VCS is required throughout leaf development, but
      normal secondary vein patterning required low temperature early in leaf
      development. The low-temperature vcs phenotype is enhanced in axr1-3 vcs double
      mutants and in vcs mutants grown in the presence of polar auxin transport
      inhibitors, however, vcs has apparently normal auxin responses. Taken together,
      these observations suggest a role for VCS in leaf blade formation.

PMID- 14660547
TI  - The pro-apoptotic gene Bax is required for the death of ectopic primordial germ
      cells during their migration in the mouse embryo.
AB  - In the mouse embryo, significant numbers of primordial germ cells (PGCs) fail to
      migrate correctly to the genital ridges early in organogenesis. These usually die
      in ectopic locations. In humans, 50% of pediatric germ line tumors arise outside
      the gonads, and these are thought to arise from PGCs that fail to die in ectopic
      locations. We show that the pro-apoptotic gene Bax, previously shown to be
      required for germ cell death during later stages of their differentiation in the
      gonads, is also expressed during germ cell migration, and is required for the
      normal death of germ cells left in ectopic locations during and after germ cell
      migration. In addition, we show that Bax is downstream of the known cell survival
      signaling interaction mediated by the Steel factor/Kit ligand/receptor
      interaction. Together, these observations identify the major mechanism that
      removes ectopic germ cells from the embryo at early stages.

PMID- 14660548
TI  - FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway.
AB  - During development, spinal cord oligodendrocyte precursors (OPCs) originate from
      the ventral, but not dorsal, neuroepithelium. Sonic hedgehog (SHH) has crucial
      effects on oligodendrocyte production in the ventral region of the spinal cord;
      however, less is known regarding SHH signalling and oligodendrocyte generation
      from neural stem cells (NSCs). We show that NSCs isolated from the dorsal spinal
      cord can generate oligodendrocytes following FGF2 treatment, a MAP kinase
      dependent phenomenon that is associated with induction of the obligate oligogenic
      gene Olig2. Cyclopamine, a potent inhibitor of hedgehog signalling, did not block
      the formation of oligodendrocytes from FGF2-treated neurosphere cultures.
      Furthermore, neurospheres generated from SHH null mice also produced
      oligodendrocytes, even in the presence of cyclopamine. These findings are
      compatible with the idea of a hedgehog independent pathway for oligodendrocyte
      generation from neural stem cells.

PMID- 14660549
TI  - Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer
      activity.
AB  - In zebrafish acerebellar (ace) embryos, because of a point mutation in fgf8, the
      isthmic constriction containing the midbrain-hindbrain boundary (MHB) organizer
      fails to form. The mutants lack cerebellar development by morphological criteria,
      and they appear to have an enlarged tectum, showing no obvious reduction in the
      tissue mass at the dorsal mesencephalic/metencephalic alar plate. To reveal the
      molecular identity of the tissues located at equivalent rostrocaudal positions
      along the neuraxis as the isthmic and cerebellar primordia in wild-types, we
      undertook a detailed analysis of ace embryos. In ace mutants, the appearance of
      forebrain and midbrain specific marker genes (otx2, dmbx1, wnt4) in the caudal
      tectal enlargement reveals a marked rostralized gene expression profile during
      early somitogenesis, followed by the lack of early and late cerebellar-specific
      gene expression (zath1/atoh1, gap43, tag1/cntn2, neurod, zebrin II). The Locus
      coeruleus (LC) derived from rostral rhombomere 1 is also absent in the mutants. A
      new interface between otx2 and epha4a suggests that the rostralization stops at
      the caudal part of rhombomere 1. The mesencephalic basal plate is also affected
      in the mutant embryos, as indicated by the caudal expansion of the diencephalic
      expression domains of epha4a, zash1b/ashb, gap43 and tag1/cntn2, and by the
      dramatic reduction of twhh expression. No marked differences are seen in cell
      proliferation and apoptotic patterns around the time the rostralization of gene
      expression becomes evident in the mutants. Therefore, locally distinct cell
      proliferation and cell death is unlikely to be the cause of the fate alteration
      of the isthmic and cerebellar primordia in the mutants. Dil cell-lineage labeling
      of isthmic primordial cells reveals that cells, at the location equivalent of the
      wild-type MHB, give rise to caudal tectum in ace embryos. This suggests that a
      caudalto-rostral transformation leads to the tectal expansion in the mutants.
      Fgf8-coated beads are able to rescue morphological MHB formation, and elicit the
      normal molecular identity of the isthmic and cerebellar primordium in ace
      embryos. Taken together, our analysis reveals that cells of the isthmic and
      cerebellar primordia acquire a more rostral, tectal identity in the absence of
      the functional MHB organizer signal Fgf8.

PMID- 14660550
TI  - Germ line stem cell differentiation in Drosophila requires gap junctions and
      proceeds via an intermediate state.
AB  - Gap junctions coordinate processes ranging from muscle contraction to ovarian
      follicle development. Here we show that the gap junction protein Zero population
      growth (Zpg) is required for germ cell differentiation in the Drosophila ovary.
      In the absence of Zpg the stem cell daughter destined to differentiate dies. The
      zpg phenotype is novel, and we used this phenotype to genetically dissect the
      process of stem cell maintenance and differentiation. Our findings suggest that
      germ line stem cells differentiate upon losing contact with their niche, that gap
      junction mediated cell-cell interactions are required for germ cell
      differentiation, and that in Drosophila germ line stem cell differentiation to a
      cystoblast is gradual.

PMID- 14660552
TI  - Calphostin-C induction of vascular smooth muscle cell apoptosis proceeds through
      phospholipase D and microtubule inhibition.
AB  - Calphostin-C, a protein kinase C inhibitor, induces apoptosis of cultured
      vascular smooth muscle cells. However, the mechanisms are not completely defined.
      Because apoptosis of vascular smooth muscle cells is critical in several
      proliferating vascular diseases such as atherosclerosis and restenosis after
      angioplasty, we decided to investigate the mechanisms underlying the calphostin-C
      induced apoptotic pathway. We show here that apoptosis is inhibited by the
      addition of exogenous phosphatidic acid, a metabolite of phospholipase D (PLD),
      and that calphostin-C inhibits completely the activities of both isoforms of PLD,
      PLD1 and PLD2. Overexpression of either PLD1 or PLD2 prevented the vascular
      smooth muscle cell apoptosis induced by serum withdrawal but not the calphostin-C
      elicited apoptosis. These data suggest that PLDs have anti-apoptotic effects and
      that complete inhibition of PLD activity by calphostin-C induces smooth muscle
      cell apoptosis. We also report that calphostin-C induced microtubule disruption
      and that the addition of exogenous phosphatidic acid inhibits calphostin-C
      effects on microtubules, suggesting a role for PLD in stabilizing the microtubule
      network. Overexpressing PLD2 in Chinese hamster ovary cells phenocopies this
      result, providing strong support for the hypothesis. Finally, taxol, a
      microtubule stabilizer, not only inhibited the calphostin-C-induced microtubule
      disruption but also inhibited apoptosis. We therefore conclude that calphostin-C
      induces apoptosis of cultured vascular smooth muscle cells through inhibiting PLD
      activity and subsequent microtubule polymerization.

PMID- 14660553
TI  - Insulin-like growth factor-1 induces an inositol 1,4,5-trisphosphate-dependent
      increase in nuclear and cytosolic calcium in cultured rat cardiac myocytes.
AB  - In the heart, insulin-like growth factor-1 (IGF-1) is a pro-hypertrophic and anti
      apoptotic peptide. In cultured rat cardiomyocytes, IGF-1 induced a fast and
      transient increase in Ca(2+)(i) levels apparent both in the nucleus and cytosol,
      releasing this ion from intracellular stores through an inositol 1,4,5
      trisphosphate (IP(3))-dependent signaling pathway. Intracellular IP(3) levels
      increased after IGF-1 stimulation in both the presence and absence of
      extracellular Ca(2+). A different spatial distribution of IP(3) receptor isoforms
      in cardiomyocytes was found. Ryanodine did not prevent the IGF-1-induced increase
      of Ca(2+)(i) levels but inhibited the basal and spontaneous Ca(2+)(i)
      oscillations observed when cardiac myocytes were incubated in Ca(2+)-containing
      resting media. Spatial analysis of fluorescence images of IGF-1-stimulated
      cardiomyocytes incubated in Ca(2+)-containing resting media showed an early
      increase in Ca(2+)(i), initially localized in the nucleus. Calcium imaging
      suggested that part of the Ca(2+) released by stimulation with IGF-1 was
      initially contained in the perinuclear region. The IGF-1-induced increase on
      Ca(2+)(i) levels was prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid-AM, thapsigargin, xestospongin C, 2-aminoethoxy diphenyl borate,
      U-73122, pertussis toxin, and betaARKct (a peptide inhibitor of Gbetagamma
      signaling). Pertussis toxin also prevented the IGF-1-dependent IP(3) mass
      increase. Genistein treatment largely decreased the IGF-1-induced changes in both
      Ca(2+)(i) and IP(3). LY29402 (but not PD98059) also prevented the IGF-1-dependent
      Ca(2+)(i) increase. Both pertussis toxin and U73122 prevented the IGF-1-dependent
      induction of both ERKs and protein kinase B. We conclude that IGF-1 increases
      Ca(2+)(i) levels in cultured cardiac myocytes through a Gbetagamma subunit of a
      pertussis toxin-sensitive G protein-PI3K-phospholipase C signaling pathway that
      involves participation of IP(3).

PMID- 14660554
TI  - Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar
      and beta cells.
AB  - How different extracellular stimuli can evoke different spatiotemporal Ca2+
      signals is uncertain. We have elucidated a novel paradigm whereby different
      agonists use different Ca2+-storing organelles ("organelle selection") to evoke
      unique responses. Some agonists select the endoplasmic reticulum (ER), and others
      select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that
      mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and
      bombesin exclusively select the ER Ca2+ store, whereas cholecystokinin
      additionally recruits a lysosome-related organelle. Similarly, in a pancreatic
      beta cell line MIN6, acetylcholine selects only the ER, whereas glucose mobilizes
      Ca2+ from a lysosome-related organelle. We also show that the key to organelle
      selection is the agonist-specific coupling messenger(s) such that the ER is
      selected by recruitment of inositol 1,4,5-trisphosphate (or cADP-ribose), whereas
      lysosome-related organelles are selected by NAADP.

PMID- 14660555
TI  - The N-terminal SH4 region of the Src family kinase Fyn is modified by methylation
      and heterogeneous fatty acylation: role in membrane targeting, cell adhesion, and
      spreading.
AB  - The N-terminal SH4 domain of Src family kinases is responsible for promoting
      membrane binding and plasma membrane targeting. Most Src family kinases contain
      an N-terminal Met-Gly-Cys consensus sequence that undergoes dual acylation with
      myristate and palmitate after removal of methionine. Previous studies of Src
      family kinase fatty acylation have relied on radiolabeling of cells with
      radioactive fatty acids. Although this method is useful for verifying that a
      given fatty acid is attached to a protein, it does not reveal whether other fatty
      acids or other modifying groups are attached to the protein. Here we use matrix
      assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry
      to identify fatty acylated species of the Src family kinase Fyn. Our results
      reveal that Fyn is efficiently myristoylated and that some of the myristoylated
      proteins are also heterogeneously S-acylated with palmitate, palmitoleate,
      stearate, or oleate. Furthermore, we show for the first time that Fyn is
      trimethylated at lysine residues 7 and/or 9 within its N-terminal region. Both
      myristoylation and palmitoylation were required for methylation of Fyn. However,
      a general methylation inhibitor had no inhibitory effect on myristoylation and
      palmitoylation of Fyn, suggesting that methylation occurs after myristoylation
      and palmitoylation. Lysine mutants of Fyn that could not be methylated failed to
      promote cell adhesion and spreading, suggesting that methylation is important for
      Fyn function.

PMID- 14660556
TI  - Effect of the structure of the N terminus of tropomyosin on tropomodulin
      function.
AB  - Tropomodulins (Tmod) bind to the N terminus of tropomyosin and cap the pointed
      end of actin filaments. Tropomyosin alone also inhibits the rate of actin
      depolymerization at the pointed end of filaments. Here we have defined 1) the
      structural requirements of the N terminus of tropomyosin important for regulating
      the pointed end alone and with erythrocyte Tmod (Tmod1), and 2) the Tmod1
      subdomains required for binding to tropomyosin and for regulating the pointed
      end. Changes in pyrene-actin fluorescence during polymerization and
      depolymerization were measured with actin filaments blocked at the barbed end
      with gelsolin. Three tropomyosin isoforms differently influence pointed end
      dynamics. Recombinant TM5a, a short non-muscle alpha-tropomyosin, inhibited
      depolymerization. Recombinant (unacetylated) TM2 and N-acetylated striated muscle
      TM (stTM), long alpha-tropomyosin isoforms with the same N-terminal sequence,
      different from TM5a, also inhibited depolymerization but were less effective than
      TM5a. All blocked the pointed end with Tmod1 in the order of effectiveness TM5a
      >stTM >TM2, showing the importance of the N-terminal sequence and modification.
      Tmod1-(1-344), lacking the C-terminal 15 residues, did not nucleate
      polymerization but blocked the pointed end with all three tropomyosin isoforms as
      does a shorter fragment, Tmod1-(1-92), lacking the C-terminal "capping" domain
      though higher concentrations were required. An even shorter fragment, Tmod1-(1
      48), bound tropomyosin but did not influence actin filament elongation.
      Tropomyosin-Tmod may function to locally regulate cytoskeletal dynamics in cells
      by stabilizing actin filaments.

PMID- 14660557
TI  - Mutant (R406W) human tau is hyperphosphorylated and does not efficiently bind
      microtubules in a neuronal cortical cell model.
AB  - Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is an
      autosomal dominant neurodegenerative disorder caused by mutations in the gene
      that encodes for tau, a microtubule-binding protein. Neuropathologically the
      disease is characterized by extensive neuronal loss in the frontal and temporal
      lobes and the filamentous accumulation of hyperphosphorylated tau. The R406W
      missense mutation was originally described in an American and a Dutch family.
      Although R406W tau is hyperphosphorylated in FTDP-17 cases, R406W tau expressed
      in cell model systems has not shown increased phosphorylation. The purpose of
      this study was to establish a neuronal model system in which the phosphorylation
      of R406W tau is increased and thus more representative of the in vivo situation.
      To accomplish this goal immortalized mouse cortical cells that express low levels
      of endogenous tau were stably transfected with human wild type or R406W tau. In
      this neuronal model R406W tau was more highly phosphorylated at numerous epitopes
      and showed decreased microtubule binding compared with wild type tau, an effect
      that could be reversed by dephosphorylation. In addition the expression of R406W
      tau in the cortical cells resulted in increased cell death as compared with wild
      type tau-expressing cells when the cells were exposed to an apoptotic stressor.
      These results indicate that in an appropriate cellular context R406W tau is
      hyperphosphorylated, which leads to decreased microtubule binding. Furthermore,
      expression of R406W tau sensitized cells to apoptotic stress, which may
      contribute to the neuronal cell loss that occurs in this FTDP-17 tauopathy.

PMID- 14660558
TI  - Cell cycle-dependent accumulation in vivo of transposition-competent complexes
      between recombination signal ends and full-length RAG proteins.
AB  - V(D)J recombination is initiated by a specialized transposase consisting of RAG-1
      and RAG-2. Because full-length RAG proteins are insoluble under physiologic
      conditions, most previous analyses of RAG activity in vitro have used truncated
      core RAG-1 and RAG-2 fragments. These studies identified an intermediate in V(D)J
      recombination, the signal end complex (SEC), in which core RAG proteins remain
      associated with recombination signal sequences at the cleaved signal ends. From
      transfected cells expressing affinity-tagged RAG proteins, we have isolated in
      vivo assembled SECs containing full-length RAG proteins and cleaved recombination
      substrates. SEC formation in vivo did not require the repair proteins DNA
      dependent protein kinase, Ku80, or XRCC4. In the presence of full-length RAG-2,
      SEC formation in vivo was cell cycle-regulated and restricted to the G(0)/G(1)
      phases. In contrast, complexes accumulated throughout cell cycle in cells
      expressing a RAG-2 CDK2 phosphorylation site mutant. Both core and full-length
      SECs supported transposition in vitro with similar efficiencies. Intracellular
      SECs, which are likely to persist in the absence of coding ends, represent
      potential donors whose transposition is not suppressed by the non-core regions of
      the RAG proteins.

PMID- 14660559
TI  - Molecular characterization and role of bovine upstream stimulatory factor 1 and 2
      in the regulation of the prostaglandin G/H synthase-2 promoter in granulosa
      cells.
AB  - The transcriptional activation of the prostaglandin G/H synthase-2 (PGHS-2) gene
      in granulosa cells is required for ovulation. To directly study the ability of
      upstream stimulatory factor 1 (USF1) and USF2 to trans-activate the bovine PGHS-2
      promoter in granulosa cells, USF1 or USF2 expression vectors were cotransfected
      with the PGHS-2/luciferase (LUC) chimeric construct, -149/-2PGHS-2.LUC. Results
      revealed that overexpression of USF1 or USF2 caused a marked and significant
      increase in basal and forskolin-inducible promoter activities (p<0.05), and these
      effects were dependent on the presence of a consensus E-box cis-element within
      the promoter fragment. Co-transfections with different N- and C-terminal
      truncated USF mutants led to significant reductions in promoter activation, as
      compared with full-length constructs (p<0.05), thus allowing identification of
      putative bovine USF functional domains. Overexpression of a USF2 truncated mutant
      lacking the first 220 residues (U2Delta1-220) acted as a dominant negative mutant
      and blocked endogenous and USF-stimulated PGHS-2 promoter activation.
      Interestingly, transfections with U2Delta1-220 blocked the forskolin-dependent
      induction of PGHS-2 mRNA in granulosa cells, whereas transfections with full
      length USF2 increased PGHS-2 transcript levels. Immunoblot analyses confirmed
      overexpression of full-length and truncated USF proteins, and electrophoretic
      mobility shift assays (EMSAs) and supershift EMSAs established that the observed
      effects were dependent on specific interactions between USF proteins and the
      consensus E-box cis-element. Stimulation of cells with forskolin increased,
      whereas treatment of extracts with phosphatase decreased USF binding activities
      to the E-box. Thus, this study presents for the first time direct evidence for a
      role of USF proteins in the regulation of the PGHS-2 promoter in preovulatory
      granulosa cells.

PMID- 14660560
TI  - Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment:
      insights into substrate recognition, tRNA binding, and angiogenesis activity.
AB  - Human tryptophanyl-tRNA synthetase (hTrpRS) produces a full-length and three N
      terminus-truncated forms through alternative splicing and proteolysis. The
      shortest fragment that contains the aminoacylation catalytic fragment (T2-hTrpRS)
      exhibits the most potent angiostatic activity. We report here the crystal
      structure of T2-hTrpRS at 2.5 A resolution, which was solved using the multi
      wavelength anomalous diffraction method. T2-hTrpRS shares a very low sequence
      homology of 22% with Bacillus stearothermophilus TrpRS (bTrpRS); however, their
      overall structures are strikingly similar. Structural comparison of T2-hTrpRS
      with bTrpRS reveals substantial structural differences in the substrate-binding
      pocket and at the entrance to the pocket that play important roles in substrate
      binding and tRNA binding. T2-hTrpRS has a wide opening to the active site and
      adopts a compact conformation similar to the closed conformation of bTrpRS. These
      results suggest that mammalian and bacterial TrpRSs might use different
      mechanisms to recognize the substrate. Modeling studies indicate that tRNA binds
      with the dimeric enzyme and interacts primarily with the connective polypeptide 1
      of hTrpRS via its acceptor arm and the alpha-helical domain of hTrpRS via its
      anticodon loop. Our results also suggest that the angiostatic activity is likely
      located at the alpha-helical domain, which resembles the short chain cytokines.

PMID- 14660561
TI  - Homer protein increases activation of Ca2+ sparks in permeabilized skeletal
      muscle.
AB  - Members of the Homer family of proteins are known to form multimeric complexes
      capable of cross-linking plasma membrane channels (e.g. metabotropic glutamate
      receptor) and intracellular Ca2+ release channels (e.g. inositol trisphosphate
      receptor) in neurons, which potentiates Ca2+ release. Recent work has
      demonstrated direct interaction of Homer proteins with type 1 and type 2
      ryanodine receptor (RyR) isoforms. Moreover, Homer proteins have been shown to
      modulate RyR-dependent Ca2+ release in isolated channels as well as in whole cell
      preparations. We now show that long and short forms of Homer H1 (H1c and H1-EVH1)
      are potent activators of Ca2+ release via RyR in skeletal muscle fibers (e.g.
      Ca2+ sparks) and potent modulators of ryanodine binding to membranes enriched
      with RyR, with H1c being significantly more potent than H1-EVH1. Homer did not
      significantly alter the spatio-temporal properties of the sparks, demonstrating
      that Homer increases the rate of opening of RyRs, with no change in the overall
      RyR channel open time and amount of Ca2+ released during a spark. No changes in
      Ca2+ spark frequency or properties were observed using a full-length H1c with
      mutation in the EVH1 binding domain (H1c-G89N). One novel finding with each Homer
      agonist (H1c and H1-EVH1) was that in combination their actions on [3H]ryanodine
      binding was additive, an effect also observed for these Homer agonists in the
      Ca2+ spark studies. Finally, in Ca2+ spark studies, excess H1c-G89N prevented the
      effects of H1c in a dominant negative manner. Taken together our results suggest
      that the EVH1 domain is critical for the agonist behavior on Ca2+ sparks and
      ryanodine binding, and that the coiled-coil domain, present in long but not short
      form Homer, confers an increase in agonist potential apparently through the
      multimeric association of Homer ligand.

PMID- 14660562
TI  - Crystal structure of a human peptidyl-tRNA hydrolase reveals a new fold and
      suggests basis for a bifunctional activity.
AB  - Peptidyl-tRNA hydrolase (Pth) activity releases tRNA from the premature
      translation termination product peptidyl-tRNA. Two different enzymes have been
      reported to encode such activity, Pth present in bacteria and eukaryotes and Pth2
      present in archaea and eukaryotes. Here we report the crystallographic structure
      of the Homo sapiens Pth2 at a 2.0-A resolution as well as its catalytic
      properties. In contrast to the structure of Escherichia coli Pth, H. sapiens Pth2
      has an alpha/beta fold with a four-stranded antiparallel beta-sheet in its core
      surrounded by two alpha-helices on each side. This arrangement of secondary
      structure elements generates a fold not previously reported. Its catalytic
      efficiency is comparable with that reported for the archaeal Sulfolobus
      solfataricus Pth2 and higher than that of the bacterial E. coli Pth. Several
      lines of evidence target the active site to two close loops with highly conserved
      residues. This active site architecture is unrelated to that of E. coli Pth. In
      addition, intermolecular contacts in the crystal asymmetric unit cell suggest a
      likely surface for protein-protein interactions related to the Pth2-mediated
      apoptosis.

PMID- 14660563
TI  - Nek9, a novel FACT-associated protein, modulates interphase progression.
AB  - The heterodimeric Spt16-Pob3/DUF/FACT complex is a class of chromatin structure
      modulators with important roles in replication and transcription. Although
      regarded as a transcription elongator for chromatin template, little is known
      about the mode of action and involvement in other molecular processes of the
      mammalian FACT. Here we report the identification of a novel interacting and
      functional partner of FACT, Nek9. Nek9 forms a stable, approximately 600-kDa
      complex with FACT in the interphase nuclei. Its active form is characterized by
      phosphorylation-dependent electrophoretic mobility shift and phosphorylation at a
      conserved residue within the activation loop (Thr(210)). When complexed with
      FACT, Nek9 exhibits markedly elevated phosphorylation on Thr(210). Cell cycle
      analysis on the Nek9(dsRNAi) cells directly implicated Nek9 in maintaining proper
      G(1) and S progression, a role temporally correlated to the formation of a
      phospho-Nek9-FACT complex. Collectively, these observations provide evidence that
      Nek9, potentially as an active enzymatic partner of FACT, mediates certain FACT
      associated cellular processes, which are ultimately essential for interphase
      progression.

PMID- 14660564
TI  - Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl
      methyltransferase involved in the regulation of protein phosphatase 2A activity.
AB  - The important role of the serine/threonine protein phosphatase 2A (PP2A) in
      various cellular processes requires a precise and dynamic regulation of PP2A
      activity, localization, and substrate specificity. The regulation of the function
      of PP2A involves the reversible methylation of the COOH group of the C-terminal
      leucine of the catalytic subunit, which, in turn, controls the enzyme's
      heteromultimeric composition and confers different protein recognition and
      substrate specificity. We have determined the structure of PPM1, the yeast
      methyltransferase responsible for methylation of PP2A. The structure of PPM1
      reveals a common S-adenosyl-l-methionine-dependent methyltransferase fold, with
      several insertions conferring the specific function and substrate recognition.
      The complexes with the S-adenosyl-l-methionine methyl donor and the S-adenosyl-l
      homocysteine product and inhibitor unambiguously revealed the co-substrate
      binding site and provided a convincing hypothesis for the PP2A C-terminal peptide
      binding site. The structure of PPM1 in a second crystal form provides clues to
      the dynamic nature of the PPM1/PP2A interaction.

PMID- 14660565
TI  - Platelet-derived growth factor receptor-mediated signal transduction from
      endosomes.
AB  - Although accumulated evidence supports the concept of endosomal signaling of
      receptor tyrosine kinases, most results are generated from studies of epidermal
      growth factor receptor (EGFR). It is not clear whether the concept of endosomal
      signaling could be generally applied to the other receptor tyrosine kinases. For
      example, platelet-derived growth factor receptor (PDGFR) is very similar to EGFR
      in terms of both signaling and trafficking; however, little is known about the
      endosomal signaling of PDGFR. In this research, we applied the same approaches
      from our recent studies regarding EGFR endosomal signaling to investigate the
      endosomal signaling of PDGFR. We showed in this communication that we are able to
      establish a system that allows the specific activation of endosome-associated
      PDGFR without the activation of the plasma membrane-associated PDGFR and without
      disrupting the overall endocytosis pathway. By using this system, we showed that
      endosomal activation of PDGFR recruits various signaling proteins including Grb2,
      SHC, phospholipase C-gamma1, and the p85alpha subunit of phosphatidylinositol 3
      kinase into endosomes and forms signaling complexes with PDGFR. We also showed
      that endosomal PDGFR signaling is sufficient to activate the major signaling
      pathways implicated in cell proliferation and survival. Moreover, we demonstrate
      that endosomal PDGFR signaling is sufficient to generate physiological output
      including cell proliferation and cell survival.

PMID- 14660566
TI  - Overexpression of lipoprotein lipase in transgenic Watanabe heritable
      hyperlipidemic rabbits improves hyperlipidemia and obesity.
AB  - Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the
      triglyceride-rich lipoproteins and plays a critical role in lipoprotein and free
      fatty acid metabolism. Genetic manipulation of LPL may be beneficial in the
      treatment of hypertriglyceridemias, but it is unknown whether increased LPL
      activity may be effective in lowering plasma cholesterol and improving insulin
      resistance in familial hypercholesterolemic patients. To test the hypothesis that
      stimulation of LPL expression may be used as an adjunctive therapy for treatment
      of homozygous familial hypercholesterolemia, we have generated transgenic (Tg)
      Watanabe heritable hyperlipidemic (WHHL) rabbits that overexpress the human LPL
      transgene and compared their plasma lipid levels, glucose metabolism, and body
      fat accumulation with those of non-Tg WHHL rabbits. Overexpression of LPL
      dramatically ameliorated hypertriglyceridemia in Tg WHHL rabbits. Furthermore,
      increased LPL activity in male Tg WHHL rabbits also corrected
      hypercholesterolemia (544 +/- 52 in non-Tg versus 227 +/- 29 mg/dl in Tg, p <
      0.01) and reduced body fat accumulation by 61% (323 +/- 27 in non-Tg versus 125
      +/- 21ginTg, p < 0.01), suggesting that LPL plays an important role in mediating
      plasma cholesterol homeostasis and adipose accumulation. In addition,
      overexpression of LPL significantly suppressed high fat diet-induced obesity and
      insulin resistance in Tg WHHL rabbits. These results imply that systemic
      elevation of LPL expression may be potentially useful for the treatment of
      hyperlipidemias, obesity, and insulin resistance.

PMID- 14660567
TI  - The efficient functioning of photosynthesis and respiration in Synechocystis sp.
      PCC 6803 strictly requires the presence of either cytochrome c6 or plastocyanin.
AB  - In cyanobacteria, cytochrome c6 and plastocyanin are able to replace each other
      as redox carriers in the photosynthetic and respiratory electron transport chains
      with the synthesis of one or another protein being regulated by the copper
      concentration in the culture medium. However, the presence of a third
      unidentified electron carrier has been suggested. To address this point, we have
      constructed two deletion mutants of the cyanobacterium Synechocystis sp. PCC
      6803, each variant lacking either the petE or petJ gene, which respectively codes
      for the copper or heme protein. The photoautotrophic and heterotrophic growth
      rate of the two mutants in copper-free and copper-supplemented medium as well as
      their photosystem I reduction kinetics in vivo were compared with those of wild
      type cells. The two mutant strains grow at equivalent rates and show similar in
      vivo photosystem I reduction kinetics as wild-type cells when cultured in media
      that allow the expression of just one of the two electron donor proteins, but
      their ability to grow and reduce photosystem I is much lower when neither
      cytochrome c6 nor plastocyanin is expressed. These findings indicate that the
      normal functioning of the cyanobacterial photosynthetic and respiratory chains
      obligatorily depends on the presence of either cytochrome c6 or plastocyanin.

PMID- 14660568
TI  - Reconstitution of phosphatidylserine transport from chemically defined donor
      membranes to phosphatidylserine decarboxylase 2 implicates specific lipid domains
      in the process.
AB  - Phosphatidylserine (PtdSer) is transported from its site of synthesis in the
      endoplasmic reticulum to the locus of PtdSer decarboxylase 2 (Psd2p) in the
      Golgi/vacuole and decarboxylated to form phosphatidylethanolamine. Recent
      biochemical and genetic evidence has implicated the C2 domain of Psd2p and a
      membrane-bound form of the phosphatidylinositol binding/transfer protein, PstB2p,
      as essential for this transport process. We devised a reconstituted system in
      which chemically defined donor membranes function to transfer PtdSer to the
      biological acceptor membranes containing Psd2p. The transfer of PtdSer is poor
      when the donor membranes have a high degree of curvature but markedly enhanced
      when the membranes are relatively planar (> or =400-nm diameter). PtdSer transfer
      is also dependent upon both the bulk and the surface concentrations of the lipid,
      with pure PtdSer vesicles acting as the most efficient donors at all
      concentrations. The lipid transfer from donor membranes containing either 100%
      PtdSer or 50% PtdSer at a fixed concentration (e.g. 250 microM PtdSer) differs by
      a factor of 20. Surface dilution of PtdSer by choline, ethanolamine, glycerol,
      and inositol phospholipids markedly inhibits PtdSer transfer, whereas
      phosphatidic acid (PtdOH) stimulates the transfer. Most importantly, the transfer
      of PtdSer from liposomes to Psd2p fails to occur in acceptor membranes from
      strains lacking PstB2p or the C2 domain of Psd2p. These data support a model for
      PtdSer transport from planar domains highly enriched in PtdSer or in PtdSer plus
      PtdOH.

PMID- 14660569
TI  - Production of phosphatidylinositol 5-phosphate by the phosphoinositide 3
      phosphatase myotubularin in mammalian cells.
AB  - MTM1, the gene encoding myotubularin (MTM1), is mutated in the X-linked
      myotubular myopathy (XLMTM), a severe genetic muscular disorder. MTM1 is a
      phosphoinositide phosphatase hydrolyzing phosphatidylinositol 3-phosphate
      (PtdIns(3)P) in yeast and in vitro. Because this lipid is implicated in the
      regulation of vesicular trafficking, we used established cell lines from XLMTM
      patients to evaluate whether the lack of endogenous MTM1 expression could affect
      PtdIns(3)P labeling patterns. Our results showed that the vesicular trafficking
      related to early endosomes was not significantly affected in the XLMTM cell lines
      compared with control cells. However, in addition to PtdIns(3)P, we found that
      MTM1 can hydrolyze phosphatidylinositol 3,5-bisphosphate both in vitro and in
      mammalian cells. Using a mass assay, we demonstrated that the product generated
      is phosphatidylinositol 5-phosphate (PtdIns(5)P), a recently discovered
      phosphoinositide, the function of which is still unknown. In L6 myotubes
      overexpressing MTM1, hyperosmotic shock induced an increase in the mass level of
      PtdIns(5)P that was reduced by 50% upon overexpression of the MTM1 inactive
      mutant D278A. These data demonstrate for the first time a role for MTM1 in the
      production of PtdIns(5)P in mammalian cells, suggesting that the lack of
      transformation of phosphatidylinositol 3,5-bisphosphate into PtdIns(5)P might be
      an important component in the etiology of myotubular myopathy.

PMID- 14660570
TI  - Cytoglobin is a respiratory protein in connective tissue and neurons, which is up
      regulated by hypoxia.
AB  - Cytoglobin is a recently discovered vertebrate globin distantly related to
      myoglobin, and its function is unknown. Here we present the first detailed
      analysis of the distribution and expression of cytoglobin. Northern and Western
      blotting experiments show the presence of cytoglobin mRNA and protein in a broad
      range of tissues. Quantitative PCR demonstrates an up-regulation of cytoglobin
      mRNA levels in rat heart and liver under hypoxic conditions (22 and 44 h of 9%
      oxygen). Immunofluorescence studies with three antibodies directed against
      different epitopes of the protein consistently show cytoglobin in connective
      tissue fibroblasts as well as in hepatic stellate cells. Cytoglobin is also
      present in chondroblasts and osteoblasts and shows a decreased level of
      expression upon differentiation to chondrocytes and osteocytes. Cytoglobin is
      located in the cytoplasm of these cell types. Evidence against an exclusively
      nuclear localization of cytoglobin, as recently proposed, is also provided by
      transfection assays with green fluorescent protein fusion constructs, which
      demonstrates the absence of an active nuclear import. The differential expression
      of cytoglobin argues against a general respiratory function of this molecule, but
      rather indicates a connective tissue-specific function. We hypothesize that
      cytoglobin may be involved in collagen synthesis. Cytoglobin expression was also
      observed in some neuronal subpopulations of the central and the peripheral
      nervous systems. Surprisingly, cytoglobin is localized in both the cytoplasm and
      nucleus of neurons, indicating a possible additional role of this protein in
      neuronal tissues.

PMID- 14660571
TI  - Progastrin is directed to the regulated secretory pathway by synergistically
      acting basic and acidic motifs.
AB  - Bioactivation of prohormones occurs in the granules of the regulated secretory
      pathway of endocrine cells, which release hormones in response to external
      stimulation. How secretory granules are formed and how the cargo is selected is
      still unclear, but it has been shown for several prohormones and processing
      enzymes that domains within the prohormone structure can act as "sorting signals"
      for this pathway. The domains mediate interactions with other proteins or with
      the membrane or facilitate aggregation of the (pro)peptides. We have now searched
      for domains in progastrin that are active in sorting the prohormone into
      secretory granules. Truncation studies showed that the N-terminal 30 residues of
      progastrin are dispensable, whereas the last 49 residues are sufficient for
      correct biosynthesis of bioactive gastrin. Thus, further N-terminal truncation
      abolished gastrin expression. C-terminal truncation of 8 residues resulted in an
      increase in basal secretion as did point mutations in the dibasic processing
      sites of progastrin. These mutants, however, still responded to secretagogues,
      suggesting a residual sorting capacity to the regulated pathway. Amino acid
      substitutions in an acidic, polyglutamate motif within gastrin-17, the main
      bioactive, cellular gastrin form, did not alter secretion per se, but when these
      residues were substituted in C-terminally truncated mutants, double mutants
      increased in basal secretion and did not respond to secretagogue stimulation.
      This implies that the mutants are constitutively secreted. Our data suggest that
      the dibasic processing sites constitute the most important sorting domain of
      progastrin, and these sites act in synergy with the acidic domain.

PMID- 14660573
TI  - Modulation of the electron redistribution in mixed valence cytochrome C oxidase
      by protein conformational changes.
AB  - The redistribution of two electrons in the four redox centers of cytochrome c
      oxidase following photodissociation of CO from the CO-bound mixed valence species
      has been examined by resonance Raman spectroscopy. To account for both the
      kinetic data, obtained from 5 micros to 2 ms, and the equilibrium results, a
      model is proposed in which the electron redistribution is modulated by a protein
      conformation transition from a nascent P(1) state to a relaxed P(2) state in a
      time window longer than 2 ms. In this model, all six possible two-electron
      reduced species are considered. The high population of species with a one
      electron reduced binuclear center, in which the spectrum of heme a(3) is
      perturbed by the redox state of Cu(B), accounts for the significant residuals in
      the fitting of the kinetic data with four standard spectra derived from redox
      species with either zero or two electrons in the binuclear center. Under
      equilibrium conditions, the conformational change to the P(2) state destabilizes
      the redox states with only one electron in the binuclear center with respect to
      those with either zero or two electrons. As a result, the redox equilibrium is
      perturbed, and the electrons are redistributed. A simulation based on the new
      kinetics scheme, in which the electron redistribution is modulated by the protein
      conformation, gives reasonable agreement with both the equilibrium and the
      kinetic data, demonstrating the validity of this model.

PMID- 14660572
TI  - The disulfide bonding pattern in ficolin multimers.
AB  - Ficolin is a plasma lectin, consisting of a short N-terminal multimerization
      domain, a middle collagen domain, and a C-terminal fibrinogen-like domain. The
      collagen domains assemble the subunits into trimers, and the N-terminal domain
      assembles four trimers into 12-mers. Two cysteine residues in the N-terminal
      domain are thought to mediate multimerization by disulfide bonding. We have
      generated three mutants of ficolin alpha in which the N-terminal cysteines were
      substituted by serines (Cys4, Cys24, and Cys4/Cys24). The N-terminal cysteine
      mutants were produced in a mammalian cell expression system, purified by affinity
      chromatography, and analyzed under nondenaturing conditions to resolve the
      multimer structure of the native protein and under denaturing conditions to
      resolve the disulfide-linked structure. Glycerol gradient sedimentation and
      electron microscopy in nondenaturing conditions showed that plasma and
      recombinant wild-type protein formed 12-mers. The Cys4 mutant also formed 12
      mers, but Cys24 and Cys4/Cys24 mutants formed only trimers. This means that
      protein interfaces containing Cys4 are stable as noncovalent protein-protein
      interactions and do not require disulfides, whereas those containing Cys24-Cys24
      require the disulfides for stability. Proteins were also analyzed by nonreducing
      SDS-PAGE to show the covalent structure under denaturing conditions. Wild-type
      ficolin was covalently linked into 12-mers, whereas elimination of either Cys4 or
      Cys24 gave dimers and monomers. We present a model in which symmetric Cys24-Cys24
      disulfide bonds between trimers are the basis for multimerization. The model may
      also be relevant to collectin multimers.

PMID- 14660574
TI  - Structural insights into substrate specificity and function of glucodextranase.
AB  - A glucodextranase (iGDase) from Arthrobacter globiformis I42 hydrolyzes alpha-1,6
      glucosidic linkages of dextran from the non-reducing end to produce beta-D
      glucose via an inverting reaction mechanism and classified into the glycoside
      hydrolase family 15 (GH15). Here we cloned the iGDase gene and determined the
      crystal structures of iGDase of the unliganded form and the complex with acarbose
      at 2.42-A resolution. The structure of iGDase is composed of four domains N, A,
      B, and C. Domain A forms an (alpha/alpha)(6)-barrel structure and domain N
      consists of 17 antiparallel beta-strands, and both domains are conserved in
      bacterial glucoamylases (GAs) and appear to be mainly concerned with catalytic
      activity. The structure of iGDase complexed with acarbose revealed that the
      positions and orientations of the residues at subsites -1 and +1 are nearly
      identical between iGDase and GA; however, the residues corresponding to subsite
      3, which form the entrance of the substrate binding pocket, and the position of
      the open space and constriction of iGDase are different from those of GAs. On the
      other hand, domains B and C are not found in the bacterial GAs. The primary
      structure of domain C is homologous with a surface layer homology domain of
      pullulanases, and the three-dimensional structure of domain C resembles the
      carbohydrate-binding domain of some glycohydrolases.

PMID- 14660575
TI  - Properties of some variants of human beta2-microglobulin and amyloidogenesis.
AB  - Three variants of human beta(2)-microglobulin (beta(2)-m) were compared with wild
      type protein. For two variants, namely the mutant R3Abeta(2)-m and the form
      devoid of the N-terminal tripeptide (DeltaN3beta(2)-m), a reduced unfolding free
      energy was measured compared with wild-type beta(2)-m, whereas an increased
      stability was observed for the mutant H31Ybeta(2)-m. The solution structure could
      be determined by (1)H NMR spectroscopy and restrained modeling only for
      R3Abeta(2)-m that showed the same conformation as the parent species, except for
      deviations at the interstrand loops. Analogous conclusions were reached for
      H31Ybeta(2)-m and DeltaN3beta(2)-m. Precipitation and unfolding were observed
      over time periods shorter than 4-6 weeks with all the variants and, sometimes,
      with wild-type protein. The rate of structured protein loss from solution as a
      result of precipitation and unfolding always showed pseudo-zeroth order kinetics.
      This and the failure to observe an unfolded species without precipitation suggest
      that a nucleated conformational conversion scheme should apply for beta(2)-m
      fibrillogenesis. The mechanism is consistent with the previous and present
      results on beta(2)-m amyloid transition, provided a nucleated oligomeric species
      be considered the stable intermediate of fibrillogenesis, the monomeric
      intermediate being the necessary transition step along the pathway from the
      native protein to the nucleated oligomer.

PMID- 14660576
TI  - Role of amphiphysin II in somatostatin receptor trafficking in neuroendocrine
      cells.
AB  - Amphiphysins are SH3 domain-containing proteins thought to function in clathrin
      mediated endocytosis. To investigate the potential role of amphiphysin II in
      cellular trafficking of G protein-coupled somatostatin (SRIF) receptors, we
      generated an AtT-20 cell line stably overexpressing amphiphysin IIb, a splice
      variant that does not bind clathrin. Endocytosis of (125)I-[d-Trp(8)]SRIF was not
      affected by amphiphysin IIb overexpression. However, the maximal binding capacity
      (B(max)) of the ligand on intact cells was significantly lower in amphiphysin IIb
      overexpressing than in non-transfected cells. This difference was no longer
      apparent when the experiments were performed on crude cell homogenates,
      suggesting that amphiphysin IIb overexpression interferes with SRIF receptor
      targeting to the cell surface and not with receptor synthesis. Accordingly,
      immunofluorescence experiments demonstrated that, in amphiphysin overexpressing
      cells, sst(2A) and sst(5) receptors were segregated in a juxtanuclear compartment
      identified as the trans-Golgi network. Amphiphysin IIb overexpression had no
      effect on corticotrophin-releasing factor 41-stimulated adrenocorticotropic
      hormone secretion, suggesting that it is not involved in the regulated secretory
      pathway. Taken together, these results suggest that amphiphysin II is not
      necessary for SRIF receptor endocytosis but is critical for its constitutive
      targeting to the plasma membrane. Therefore, amphiphysin IIb may be an important
      component of the constitutive secretory pathway.

PMID- 14660577
TI  - Expression, assay, and structure of the extracellular domain of murine carbonic
      anhydrase XIV: implications for selective inhibition of membrane-associated
      isozymes.
AB  - Carbonic anhydrase (CA) XIV is the most recently identified mammalian carbonic
      anhydrase isozyme, and its presence has been demonstrated in a number of tissues.
      Full-length CA XIV is a transmembrane protein composed of an extracellular
      catalytic domain, a single transmembrane helix, and a short intracellular
      polypeptide segment. The amino acid sequence identity of human CA XIV relative to
      the other membrane-associated isozymes (CA IV, CA IX, and CA XII) is 34-46%. We
      report here the expression and purification of both the full-length enzyme and a
      truncated, secretory form of murine CA XIV. Both forms of this isozyme are highly
      active, and both show an abrogation of activity in the presence of 0.2% SDS, in
      contrast to the behavior of murine CA IV. We also report the crystal structure of
      the extracellular domain of murine CA XIV at 2.8 A resolution and of an enzyme
      acetazolamide complex at 2.9 A resolution. The structure shows a monomeric
      glycoprotein with a topology similar to that of other mammalian CA isozymes.
      Based on the x-ray crystallographic results, we compare and contrast known
      structures of membrane-associated CA isozymes to rationalize the structural
      elements responsible for the SDS resistance of CA IV and to discuss prospects for
      the design of selective inhibitors of membrane-associated CA isozymes.

PMID- 14660578
TI  - Identification of four genes necessary for biosynthesis of the modified
      nucleoside queuosine.
AB  - Queuosine (Q) is a hypermodified 7-deazaguanosine nucleoside located in the
      anticodon wobble position of four amino acid-specific tRNAs. In bacteria, Q is
      produced de novo from GTP via the 7-deazaguanosine precursor preQ1 (7-aminoethyl
      7-deazaguanine) by an uncharacterized pathway. PreQ1 is subsequently transferred
      to its specific tRNA by a tRNA-guanine transglycosylase (TGT) and then further
      modified in situ to produce Q. Here we use comparative genomics to implicate four
      gene families (best exemplified by the B. subtilis operon ykvJKLM) as candidates
      in the preQ1 biosynthetic pathway. Deletions were constructed in genes for each
      of the four orthologs in Acinetobacter. High pressure liquid chromatography
      analysis showed the Q nucleoside was absent from the tRNAs of each of four
      deletion strains. Electrospray ionization mass spectrometry confirmed the absence
      of Q in each mutant strain. Finally, introduction of the Bacillus subtilis
      ykvJKLM operon in trans complemented the Q deficiency of the two deletion mutants
      that were tested. Thus, the products of these four genes (named queC, -D, -E, and
      -F) are essential for the Q biosynthetic pathway.

PMID- 14660579
TI  - Identification of BMP and activin membrane-bound inhibitor (BAMBI), an inhibitor
      of transforming growth factor-beta signaling, as a target of the beta-catenin
      pathway in colorectal tumor cells.
AB  - The Wnt signaling pathway is activated in most human colorectal tumors.
      Mutational inactivation in the tumor suppressor adenomatous polyposis coli (APC),
      as well as activation of beta-catenin, causes the accumulation of beta-catenin,
      which in turn associates with the T cell factor/lymphoid enhancer factor
      (TCF/LEF) family of transcription factors and activates transcription of their
      target genes. Here we show that beta-catenin activates transcription of the BMP
      and activin membrane-bound inhibitor (BAMBI)/NMA gene. The expression level of
      BAMBI was found to be aberrantly elevated in most colorectal and hepatocellular
      carcinomas relative to the corresponding non-cancerous tissues. Expression of
      BAMBI in colorectal tumor cell lines was repressed by a dominant-negative mutant
      of TCF-4 or by an inhibitor of beta-catenin-TCF interaction, suggesting that beta
      catenin is responsible for the aberrant expression of BAMBI in colorectal tumor
      cells. Furthermore, overexpression of BAMBI inhibited the response of tumor cells
      to transforming growth factor-beta signaling. These results suggest that beta
      catenin interferes with transforming growth factor-beta-mediated growth arrest by
      inducing the expression of BAMBI, and this may contribute to colorectal and
      hepatocellular tumorigenesis.

PMID- 14660580
TI  - Divergent evolution in metabotropic glutamate receptors. A new receptor activated
      by an endogenous ligand different from glutamate in insects.
AB  - The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors
      involved in the regulation of glutamatergic synapses. Surprisingly, the evolution
      arily distant Drosophila mGluR shares a very similar pharmacological profile with
      its mammalian orthologues (mGlu2R and mGlu3R). Such a conservation in ligand
      recognition indicates a strong selective pressure during evolution to maintain
      the ligand recognition selectivity of mGluRs and suggests that structural
      constraints within the ligand binding pocket (LBP) would hinder divergent
      evolution. Here we report the identification of a new receptor homologous to
      mGluRs found in Anopheles gambiae, Apis mellifera, and Drosophila melanogaster
      genomes and called AmXR, HBmXR, and DmXR, respectively (the mXRs group). Sequence
      comparison associated with three-dimensional modeling of the LBP revealed that
      the residues contacting the amino acid moiety of glutamate (the alpha-COO(-) and
      NH(3)(+) groups) were conserved in mXRs, whereas the residues interacting with
      the gamma-carboxylic group were not. This suggested that the mXRs evolved to
      recognize an amino acid different from glutamate. The Drosophila cDNA encoding
      DmXR was isolated and found to be insensitive to glutamate or any other standard
      amino acid. However, a chimeric receptor with the heptahelical and intracellular
      domains of DmXR coupled to G-protein. We found that the DmX receptor was
      activated by a ligand containing an amino group, which was extracted from
      Drosophila head and from other insects (Anopheles and Schistocerca). No
      orthologue of mXR could be detected in Caenorhabditis elegans or human genomes.
      These data indicate that the LBP of the mGluRs has diverged in insects to
      recognize a new ligand.

PMID- 14660581
TI  - A hexose transporter homologue controls glucose repression in the methylotrophic
      yeast Hansenula polymorpha.
AB  - Peroxisome biogenesis and synthesis of peroxisomal enzymes in the methylotrophic
      yeast Hansenula polymorpha are under the strict control of glucose repression. We
      identified an H. polymorpha glucose catabolite repression gene (HpGCR1) that
      encodes a hexose transporter homologue. Deficiency in GCR1 leads to a pleiotropic
      phenotype that includes the constitutive presence of peroxisomes and peroxisomal
      enzymes in glucose-grown cells. Glucose transport and repression defects in a UV
      induced gcr1-2 mutant were found to result from a missense point mutation that
      substitutes a serine residue (Ser(85)) with a phenylalanine in the second
      predicted transmembrane segment of the Gcr1 protein. In addition to glucose,
      mannose and trehalose fail to repress the peroxisomal enzyme, alcohol oxidase in
      gcr1-2 cells. A mutant deleted for the GCR1 gene was additionally deficient in
      fructose repression. Ethanol, sucrose, and maltose continue to repress
      peroxisomes and peroxisomal enzymes normally and therefore, appear to have GCR1
      independent repression mechanisms in H. polymorpha. Among proteins of the hexose
      transporter family of baker's yeast, Saccharomyces cerevisiae, the amino acid
      sequence of the H. polymorpha Gcr1 protein shares the highest similarity with a
      core region of Snf3p, a putative high affinity glucose sensor. Certain features
      of the phenotype exhibited by gcr1 mutants suggest a regulatory role for Gcr1p in
      a repression pathway, along with involvement in hexose transport.

PMID- 14660582
TI  - Deoxycholic acid activates the c-Jun N-terminal kinase pathway via FAS receptor
      activation in primary hepatocytes. Role of acidic sphingomyelinase-mediated
      ceramide generation in FAS receptor activation.
AB  - We have shown previously that bile acids can activate the JNK pathway and down
      regulate cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the
      neutral pathway of bile acid biosynthesis. In this study, the mechanism(s) by
      which deoxycholic acid (DCA) activates the JNK pathway were examined. FAS
      receptor (FAS-R) and acidic sphingomyelinase (ASM)-deficient hepatocytes were
      resistant to DCA-induced activation of the JNK pathway. Activation of the JNK
      pathway (2-3-fold) in response to tumor necrosis factor-alpha was similar in both
      wild-type and FAS-R(-/-) hepatocytes. In wild-type and FAS-R(-/-) hepatocytes,
      ceramide elevation was detected as early as 2 min and peaked at 10 min after DCA
      treatment. In contrast, ASM(-/-) hepatocytes were defective in DCA-induced
      ceramide generation. Treatment with DCA resulted in movement of FAS-R to the cell
      surface, which was blocked upon treatment with brefeldin A. However, brefeldin A
      failed to block DCA-mediated JNK activation in wild-type hepatocytes. DCA-induced
      JNK activation was independent of either the epidermal growth factor receptor
      activation or free radical generation. Addition of ASM to rat hepatocytes
      activated JNK and down-regulated CYP7A1 mRNA levels. In conclusion, these results
      show that DCA activates JNK and represses CYP7A1 mRNA levels in primary
      hepatocytes via an ASM/FAS-R-dependent mechanism that is independent of either
      the epidermal growth factor receptor or free radical generation.

PMID- 14660583
TI  - Chicken avidin-related protein 4/5 shows superior thermal stability when compared
      with avidin while retaining high affinity to biotin.
AB  - The protein chicken avidin is a commonly used tool in various applications. The
      avidin gene belongs to a gene family that also includes seven other members known
      as the avidin-related genes (AVR). We report here on the extremely high thermal
      stability and functional characteristics of avidin-related protein AVR4/5, a
      member of the avidin protein family. The thermal stability characteristics of
      AVR4/5 were examined using a differential scanning calorimeter, microparticle
      analysis, and a microplate assay. Its biotin-binding properties were studied
      using an isothermal calorimeter and IAsys optical biosensor. According to these
      analyses, in the absence of biotin AVR4/5 is clearly more stable (T(m) = 107.4 +/
      0.3 degrees C) than avidin (T(m) = 83.5 +/- 0.1 degrees C) or bacterial
      streptavidin (T(m) = 75.5 degrees C). AVR4/5 also exhibits a high affinity for
      biotin (K(d) approximately 3.6 x 10(-14) m) comparable to that of avidin and
      streptavidin (K(d) approximately 10(-15) m). Molecular modeling and site-directed
      mutagenesis were used to study the molecular details behind the observed high
      thermostability. The results indicate that AVR4/5 and its mutants have high
      potential as new improved tools for applications where exceptionally high
      stability and tight biotin binding are needed.

PMID- 14660584
TI  - Phosphorylation-induced conformational changes of cystic fibrosis transmembrane
      conductance regulator monitored by attenuated total reflection-Fourier transform
      IR spectroscopy and fluorescence spectroscopy.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ABC
      protein superfamily. Phosphorylation of a regulatory domain of this protein is a
      prerequisite for activity. We analyzed the effect of protein kinase A (PKA)
      phosphorylation on the structure of purified and reconstituted CFTR protein.
      1H/2H exchange monitored by attenuated total reflection Fourier transform IR
      spectroscopy demonstrates that CFTR is highly accessible to aqueous medium.
      Phosphorylation of the regulatory (R) domain by PKA further increases this
      accessibility. More specifically, fluorescence quenching of cytosolic tryptophan
      residues revealed that the accessibility of the cytoplasmic part of the protein
      is modified by phosphorylation. Moreover, the combination of polarized IR
      spectroscopy with 1H/2H exchange suggested an increase of the accessibility of
      the transmembrane domains of CFTR. This suggests that CFTR phosphorylation can
      induce a large conformational change that could correspond either to a
      displacement of the R domain or to long range conformational changes transmitted
      from the phosphorylation sites to the nucleotide binding domains and the
      transmembrane segments. Such structural changes may provide better access for the
      solutes to the nucleotide binding domains and the ion binding site.

PMID- 14660585
TI  - Inducible expression, enzymatic activity, and origin of higher plant homologues
      of bacterial RelA/SpoT stress proteins in Nicotiana tabacum.
AB  - All living cells possess adaptive responses to environmental stress that are
      essential to ensuring cell survival. For motile organisms, this can culminate in
      avoidance or attractile behavior, but for sessile organisms such as plants,
      stress adaptation is a process of success or failure within the confines of a
      given environment. Nearly all bacterial species possess a highly evolved system
      for stress adaptation, known as the "stringent response." This ancient and
      ubiquitous regulatory response is mediated by production of a second messenger of
      general stress, the nucleotide guanosine-3',5'-(bis)pyrophosphate (ppGpp), which
      mediates reprogramming of the global transcriptional output of the cell.
      Accumulation of ppGpp is stress-induced through the enzymatic activation of the
      well known bacterial ppGpp synthetases, RelA and SpoT. We have recently
      discovered homologues of bacterial relA/spoT genes in the model plant Nicotiana
      tabacum. We hypothesize that these homologues (designated RSH genes for RelA/SpoT
      homologues) serve a stress-adaptive function in plants analogous with their
      function in bacteria. In support of this hypothesis, we find 1) inducibility of
      tobacco RSH gene expression following treatment with jasmonic acid; 2) bona fide
      ppGpp synthesis activity of purified recombinant Nt-RSH2 protein, and 3) a wide
      spread distribution of RSH gene expression in the plant kingdom. Phylogenetic
      analyses identifies a distinct phylogenetic branch for the plant RSH proteins
      with two subgroups and supports ancient symbiosis and nuclear gene transfer as a
      possible origin for these stress response genes in plants. In addition, we find
      that Nt-RSH2 protein co-purifies with chloroplasts in subcellular fractionation
      experiments. Taken together, our findings implicate a direct mode of action of
      these ppGpp synthetases with regard to plant physiology, namely regulation of
      chloroplast gene expression in response to plant defense signals.

PMID- 14660587
TI  - Binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K
      dependent gamma-glutamyl carboxylase active site induces an allosteric effect
      that may ensure processive carboxylation and regulate the release of carboxylated
      product.
AB  - Propeptides of the vitamin K-dependent proteins bind to an exosite on gamma
      glutamyl carboxylase; while they are bound, multiple glutamic acids in the gamma
      carboxyglutamic acid (Gla) domain are carboxylated. The role of the propeptides
      has been studied extensively; however, the role of the Gla domain in substrate
      binding is less well understood. We used kinetic and fluorescence techniques to
      investigate the interactions of the carboxylase with a substrate containing the
      propeptide and Gla domain of factor IX (FIXproGla41). In addition, we
      characterized the effect of the Gla domain and carboxylation on propeptide and
      substrate binding. For the propeptide of factor IX (proFIX18), FIXproGla41, and
      carboxylated FIXproGla41, the Kd values were 50, 2.5, and 19.7 nM and the koff
      values were 273 x 10(-5), 9 x 10(-5), and 37 x 10(-5) s(-1), respectively. The
      koff of proFIX18 is reduced 3-fold by FLEEL and 9-fold by the Gla domain
      (residues 1-46) of FIX. The pre-steady state rate constants for carboxylation of
      FIXproGla41 was 0.02 s(-1) in enzyme excess and 0.016 s(-1) in substrate excess.
      The steady state rate in substrate excess is 4.5 x 10(-4) s(-1). These results
      demonstrate the following. 1) The pre-steady state carboxylation rate constant of
      FIXproGla41 is significantly slower than that of FLEEL. 2) The Gla domain plays
      an allosteric role in substrate-enzyme interactions. 3) Carboxylation reduces the
      allosteric effect. 4) The similarity between the steady state carboxylation rate
      constant and product dissociation rate constant suggests that product release is
      rate-limiting. 5) The increased dissociation rate after carboxylation contributes
      to the release of product.

PMID- 14660586
TI  - Adenovirus E4 gene promotes selective endothelial cell survival and angiogenesis
      via activation of the vascular endothelial-cadherin/Akt signaling pathway.
AB  - The early 4 region (E4) of the adenoviral vectors (AdE4(+)) prolongs human
      endothelial cell (EC) survival and alters the angiogenic response, although the
      mechanisms for the EC-specific, AdE4(+)-mediated effects remain unknown. We
      hypothesized that AdE4(+) modulates EC survival through activation of the
      vascular endothelial (VE)-cadherin/Akt pathway. Here, we showed that AdE4(+), but
      not AdE4(-) vectors, selectively stimulated phosphorylation of both Akt at
      Ser(473) and Src kinase in ECs. The phosphatidylinositol 3-kinase (PI3K)
      inhibitors LY294002 and wortmannin abrogated AdE4(+) induction of both phospho
      Akt expression and prolonged EC survival. Regulation of phospho-Akt was found to
      be under the control of various factors, namely VE-cadherin activation, Src
      kinase, tyrosine kinase, extracellular signal-regulated kinase (ERK), and c-Jun N
      terminal kinase (JNK). Downstream targets of Akt signaling resulted in glycogen
      synthase kinase-3alpha/beta phosphorylation, beta-catenin up-regulation, and
      caspase-3 suppression, all of which led to AdE4(+)-mediated EC survival.
      Furthermore, infection with AdE4(+) vectors increased the angiogenic potential of
      ECs by promoting EC migration and capillary tube formation in Matrigel plugs.
      This selective AdE4(+)-mediated enhanced motility of ECs was also blocked by PI3K
      inhibitors. Taken together, these results suggest that activation of the VE
      cadherin/Akt pathway is critical for AdE4(+)-mediated survival of ECs and
      angiogenic potential.

PMID- 14660588
TI  - Functional dissection of transcription factor ZBRK1 reveals zinc fingers with
      dual roles in DNA-binding and BRCA1-dependent transcriptional repression.
AB  - The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in
      both activation and repression of gene transcription by virtue of its direct
      interaction with sequence-specific DNA-binding transcription factors. However,
      the mechanistic basis by which BRCA1 mediates the transcriptional activity of
      these regulatory proteins remains largely unknown. To clarify this issue, we have
      examined the functional interaction between BRCA1 and ZBRK1, a BRCA1-dependent
      KRAB eight zinc finger transcriptional repressor. We report here the
      identification and molecular characterization of a portable BRCA1-dependent
      transcriptional repression domain within ZBRK1 composed of zinc fingers 5-8 along
      with sequences in the unique ZBRK1 C terminus. This C-terminal repression domain
      functions in a BRCA1-, histone deacetylase-, and promoter-specific manner and is
      thus functionally distinguishable from the N-terminal KRAB repression domain in
      ZBRK1, which exhibits no BRCA1 dependence and broad promoter specificity.
      Significantly, we also find that the BRCA1-dependent transcriptional repression
      domain on ZBRK1 includes elements that modulate its sequence-specific DNA binding
      activity. These findings thus reveal the presence within ZBRK1 of functionally
      bipartite zinc fingers with dual roles in sequence-specific DNA-binding and BRCA1
      dependent transcriptional repression. We discuss the implications of these
      findings for the role of BRCA1 as ZBRK1 co-repressor.

PMID- 14660589
TI  - MtmMII-mediated C-methylation during biosynthesis of the antitumor drug
      mithramycin is essential for biological activity and DNA-drug interaction.
AB  - The antitumor drug mithramycin consists of a polyketide chromophore glycosylated
      with a trisaccharide and a disaccharide. Two post-polyketide methylations take
      place during mithramycin biosynthesis. One of these methylations has been shown
      to be very relevant for biological activity, that is the introduction of a methyl
      group at aromatic C-7. We have purified to 282- fold the MtmMII methyltransferase
      involved in this reaction. The protein is a monomer, and results from kinetic
      studies were consistent with a model for the enzyme acting via a compulsory order
      mechanism. The enzyme showed high substrate specificity and was unable to operate
      on structurally closely related molecules. Structural predictions suggest that
      the molecule is integrated by two domains, an essentially all alpha-amino domain
      and an alpha/beta-carboxyl domain displaying a variation of a Rossmann-fold
      containing the cofactor binding site. Although 7-demethyl-mithramycin did not
      show any biological activity, it was able to reach the nucleus of eukaryotic
      cells, with subsequent binding to DNA. Mithramycin and 7-demethylmithramycin were
      able to form similar complexes with Mg(2+), although their respective DNA binding
      isotherms were very different. The dinucleotide binding model fit well the
      isotherms recorded for both compounds, predicting that the C-7 methyl group was
      essential for high affinity binding to specific GC and CG sequences. Considering
      previous structural studies, we propose that this effect is performed by
      positioning the group in the floor of the minor groove, allowing the interaction
      with the third sugar moiety of the trisaccharide, d-mycarose, which is involved
      in sequence selectivity.

PMID- 14660590
TI  - Hydrolysis of third-generation cephalosporins by class C beta-lactamases.
      Structures of a transition state analog of cefotoxamine in wild-type and extended
      spectrum enzymes.
AB  - Bacterial resistance to the third-generation cephalosporins is an issue of great
      concern in current antibiotic therapeutics. An important source of this
      resistance is from production of extended-spectrum (ES) beta-lactamases by
      bacteria. The Enterobacter cloacae GC1 enzyme is an example of a class C ES beta
      lactamase. Unlike wild-type (WT) forms, such as the E. cloacae P99 and
      Citrobacter freundii enzymes, the ES GC1 beta-lactamase is able to rapidly
      hydrolyze third-generation cephalosporins such as cefotaxime and ceftazidime. To
      understand the basis for this ES activity, m-nitrophenyl 2-(2-aminothiazol-4-yl)
      2-[(Z)-methoxyimino]acetylaminomethyl phosphonate has been synthesized and
      characterized. This phosphonate was designed to generate a transition state
      analog for turnover of cefotaxime. The crystal structures of complexes of the
      phosphonate with both ES GC1 and WT C. freundii GN346 beta-lactamases have been
      determined to high resolution (1.4-1.5 Angstroms). The serine-bound analog of the
      tetrahedral transition state for deacylation exhibits a very different binding
      geometry in each enzyme. In the WT beta-lactamase the cefotaxime-like side chain
      is crowded against the Omega loop and must protrude from the binding site with
      its methyloxime branch exposed. In the ES enzyme, a mutated Omega loop adopts an
      alternate conformation allowing the side chain to be much more buried. During the
      binding and turnover of the cefotaxime substrate by this ES enzyme, it is
      proposed that ligand-protein contacts and intra-ligand contacts are considerably
      relieved relative to WT, facilitating positioning and activation of the
      hydrolytic water molecule. The ES beta-lactamase is thus able to efficiently
      inactivate third-generation cephalosporins.

PMID- 14660591
TI  - Insulin promotes rat retinal neuronal cell survival in a p70S6K-dependent manner.
AB  - The purpose of this study was to examine the role of the ribosomal protein S6
      protein kinase (p70S6K), a protein synthesis regulator, in promoting retinal
      neuronal cell survival. Differentiated R28 rat retinal neuronal cells were used
      as an experimental model. Cells were maintained in Dulbecco's modified Eagle's
      medium supplemented with 10% newborn calf serum, and during the period of
      experimentation were exposed either to the absence or presence of 10 nm insulin.
      Insulin treatment induced p70S6K, mTOR, and Akt phosphorylation, effects that
      were completely prevented by the PI3K inhibitor, LY294002. Insulin-induced
      phosphorylation of p70S6K and mTOR was prevented by the mTOR inhibitor,
      rapamycin. Apoptosis, induced by serum deprivation and evaluated by Hoechst
      staining, was inhibited by insulin treatment in R28 cells, but not in L6 muscle
      cells. This effect of insulin was also largely prevented by rapamycin. Inhibition
      of p70S6K activity by exogenous expression of a dominant negative mutant of
      p70S6K prevented insulin-induced cell survival, whereas, overexpression of wild
      type p70S6K or expression of a rapamycin resistant form of the kinase enhanced
      the effect of insulin on survival. Enhanced cell survival under the latter
      condition was accompanied by increased p70S6K activity and phosphorylation.
      Rapamycin did not inhibit insulin induced p70S6K phosphorylation and activity in
      cells transfected with the rapamycin-resistant mutant. Together, these results
      suggest that p70S6K plays a key role in insulin stimulated retinal neuronal cell
      survival.

PMID- 14660592
TI  - Increased diffusional mobility of CFTR at the plasma membrane after deletion of
      its C-terminal PDZ binding motif.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP
      regulated Cl- channel expressed at the apical plasma membrane. It has been
      proposed that the C-terminal PDZ binding motif of CFTR is required for its apical
      membrane targeting and that PDZ-domain interactions may tether CFTR to the actin
      cytoskeleton via soluble proteins including EBP50/NHERF1 and ezrin. We measured
      the diffusional mobility of human CFTR in the plasma membrane of Madin-Darby
      canine kidney cells by photobleaching of green fluorescent protein (GFP)-CFTR
      chimeras. After bleaching by a focused laser beam, GFP-CFTR fluorescence in the
      bleached membrane region recovered to approximately 90% of its initial level,
      indicating that nearly all of the CFTR was mobile. The GFP-CFTR diffusion
      coefficient (D) was 0.99 +/- 0.09 x 10(-10) cm2/s at 37 degrees C, similar to
      that of other membrane proteins. GFP-CFTR diffusion was not altered by protein
      kinase A or C activators but was blocked by paraformaldehyde and filipin. CFTR
      mutants lacking functional PDZ-binding domains (GFPCFTR-DeltaTRL and GFP-CFTR
      DeltaTRA) were also mobile with D significantly increased by approximately 60%
      compared with GFP-CFTR. However, GFP-CFTR, GFP-CFTR-Delta TRL, and GFP-CFTR
      DeltaTRA had similar mobilities (D approximately 12 x 10(-10) cm2/s) at the
      endoplasmic reticulum in brefeldin A-treated cells. Agents that modulate the
      actin cytoskeleton (cytochalasin D and jasplakinolide) altered the plasma
      membrane mobility of CFTR but not CFTR- DeltaTRL. EBP50 (NHERF1), a PDZ domain
      containing protein that interacts with the C terminus of CFTR, diffused freely in
      the cytoplasm with a diffusion coefficient of 0.9 +/- 0.1 x 10(-7) cm2/s. EBP50
      diffusion increased by approximately 2-fold after deletion of its ezrin-binding
      domain. These results indicate that wild-type CFTR is not tethered statically at
      the plasma membrane but that its diffusion is dependent on PDZ-domain
      interactions and an intact actin skeleton. PDZ-domain interactions of CFTR are
      thus dynamic and occur on a time scale of seconds or faster.

PMID- 14660593
TI  - Identification of porcine coagulation factor VIII domains responsible for high
      level expression via enhanced secretion.
AB  - Blood coagulation factor VIII has a domain structure designated A1-A2-B-ap-A3-C1
      C2. Human factor VIII is present at low concentration in normal plasma and,
      comparably, is produced at low levels in vitro and in vivo using transgenic
      expression techniques. Heterologous expression of B domain-deleted porcine factor
      VIII in mammalian cell culture is significantly greater than B domain-deleted
      human or murine factor VIII. Novel hybrid human/porcine factor VIII molecules
      were constructed to identify porcine factor VIII domains that confer high level
      expression. Hybrid human/porcine factor VIII constructs containing the porcine
      factor VIII A1 and ap-A3 domains expressed at levels comparable with recombinant
      porcine factor VIII. A hybrid construct containing only the porcine A1 domain
      expressed at intermediate levels between human and porcine factor VIII, whereas a
      hybrid construct containing the porcine ap-A3 domain expressed at levels
      comparable with human factor VIII. Additionally, hybrid murine/porcine factor
      VIII constructs containing the porcine factor VIII A1 and ap-A3 domain sequences
      expressed at levels significantly higher than recombinant murine factor VIII.
      Therefore, the porcine A1 and ap-A3 domains are necessary and sufficient for the
      high level expression associated with porcine factor VIII. Metabolic
      radiolabeling experiments demonstrated that high level expression was
      attributable to enhanced secretory efficiency.

PMID- 14660594
TI  - Membrane topology of human insig-1, a protein regulator of lipid synthesis.
AB  - Insig-1 is an intrinsic protein of the endoplasmic reticulum (ER) that regulates
      the proteolytic processing of membrane-bound sterol regulatory element-binding
      proteins (SREBPs), transcription factors that activate the synthesis of
      cholesterol and fatty acids in mammalian cells. When cellular levels of sterols
      rise, Insig-1 binds to the membranous sterol-sensing domain of SREBP cleavage
      activating protein (SCAP), retaining the SCAP/SREBP complex in the ER and
      preventing it from moving to the Golgi for proteolytic processing. Under
      conditions of sterol excess, Insig-1 also binds to the ER enzyme 3-hydroxy-3
      methylglutaryl coenzyme A (HMG CoA) reductase, facilitating its ubiquitination
      and proteasomal degradation. Here, we use protease protection, glycosylation site
      mapping, and cysteine derivitization to define the topology of the 277-amino acid
      human Insig-1. The data indicate that short segments at the N and C termini of
      Insig-1 face the cytosol. Most of the protein is buried within the membrane,
      forming six transmembrane segments separated by five short luminal and cytosolic
      loops that range from approximately 5 to 16 amino acids. The membranous nature of
      Insig-1 is consistent with its sterol-dependent binding to hydrophobic sterol
      sensing domains in SCAP and HMG CoA reductase.

PMID- 14660595
TI  - Evolutionary trace of G protein-coupled receptors reveals clusters of residues
      that determine global and class-specific functions.
AB  - G protein-coupled receptor (GPCR) activation mediated by ligand-induced
      structural reorganization of its helices is poorly understood. To determine the
      universal elements of this conformational switch, we used evolutionary tracing
      (ET) to identify residue positions commonly important in diverse GPCRs. When
      mapped onto the rhodopsin structure, these trace residues cluster into a network
      of contacts from the retinal binding site to the G protein-coupling loops. Their
      roles in a generic transduction mechanism were verified by 211 of 239 published
      mutations that caused functional defects. When grouped according to the nature of
      the defects, these residues sub-divided into three striking sub-clusters: a
      trigger region, where mutations mostly affect ligand binding, a coupling region
      near the cytoplasmic interface to the G protein, where mutations affect G protein
      activation, and a linking core in between where mutations cause constitutive
      activity and other defects. Differential ET analysis of the opsin family revealed
      an additional set of opsin-specific residues, several of which form part of the
      retinal binding pocket, and are known to cause functional defects upon mutation.
      To test the predictive power of ET, we introduced novel mutations in bovine
      rhodopsin at a globally important position, Leu-79, and at an opsin-specific
      position, Trp-175. Both were functionally critical, causing constitutive G
      protein activation of the mutants and rapid loss of regeneration after
      photobleaching. These results define in GPCRs a canonical signal transduction
      mechanism where ligand binding induces conformational changes propagated through
      adjacent trigger, linking core, and coupling regions.

PMID- 14660596
TI  - The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF complex
      for proliferation arrest.
AB  - The transcription factor CCAAT enhancer-binding protein alpha (C/EBPalpha) is a
      tumor suppressor in myeloid cells and inhibits proliferation in all cell types
      examined. C/EBPalpha interacts with the SWI/SNF chromatin-remodeling complex
      during the regulation of differentiation-specific genes. Here we show that
      C/EBPalpha fails to suppress proliferation in SWI/SNF defective cell lines after
      knock-down of SWI/SNF core components or after deletion of the SWI/SNF
      interaction domain in C/EBPalpha, respectively. Reconstitution of SWI/SNF
      function restores C/EBPalpha-dependent proliferation arrest. Our results show
      that the anti-proliferation activity of C/EBPalpha critically depends on
      components of the SWI/SNF core complex and suggest that the functional
      interaction between SWI/SNF and C/EBPalpha is a prerequisite for proliferation
      arrest.

PMID- 14660597
TI  - Geldanamycin-associated inhibition of intracellular trafficking is attributed to
      a co-purified activity.
AB  - Geldanamycin, an ansamycin antibiotic that specifically inhibits heat-shock
      protein-90 (HSP90) and its endoplasmic reticulum homologue, glucose-regulated
      protein-94 (GRP94), accelerates the degradation of selected cellular proteins. We
      showed previously that geldanamycin inhibits maturation and transport of the
      epidermal growth factor receptor in addition to accelerating its degradation
      (Supino-Rosin, L., Yoshimura, A., Yarden, Y., Elazar, Z., and Neumann, D. (2000)
      J. Biol. Chem. 275, 21850-21855). Here we demonstrate that the additional
      activities of geldanamycin on intracellular transport and protein maturation are
      related to its supply source. By combining chemical separation of Streptomyces
      hygroscopicus var. geldanus extracts and biological screens, we show that the
      geldanamycin-associated effects on intracellular transport and protein maturation
      are not mediated by geldanamycin itself but are due to the presence of an
      additional component(s). Chromatography of S. hygroscopicus var. geldanus
      extracts on a silica-gel column allowed separation between the inhibition of
      intracellular trafficking and geldanamycin-mediated degradation. One fraction
      that was devoid of geldanamycin blocked secretion of a soluble form of the
      erythropoietin receptor, retarded maturation of the epidermal growth factor
      receptor without enhancing its degradation, and blocked anterograde transport of
      a temperature-sensitive mutant of the vesicular stomatitis virus G protein
      (VSVGtsO45) from the early Golgi cisternae. This fraction was enriched (>95%) in
      17-demethylgeldanamycin. However, as synthetically derived 17
      demethylgeldanamycin did not inhibit intracellular trafficking, we concluded that
      17-demethylgeldanamycin is not the active component. We thus propose that a
      compound(s) that co-purifies with benzoquinone ansamycins inhibits intracellular
      transport. Taken together, our data demonstrate that the inhibitory effects on
      protein maturation and intracellular trafficking, previously attributed to
      geldanamycin, are mediated by another distinct moiety.

PMID- 14660598
TI  - p120 catenin associates with microtubules: inverse relationship between
      microtubule binding and Rho GTPase regulation.
AB  - p120 catenin (p120ctn), an armadillo protein and component of the cadherin
      adhesion complex, has been found recently to induce a dendritic morphology by
      regulating Rho family GTPases. We have identified specific serines within the Arm
      repeat domain that, when mutated to alanine, promote p120ctn association with
      interphase microtubules, leading to microtubule reorganization and stabilization.
      The mutant p120ctn also localized to the mitotic spindle and centrosomes. In
      contrast to wild-type p120ctn, the microtubule-associated p120ctn mutant did not
      activate Rac1 and did not induce a dendritic morphology. In addition, we show
      that a basic motif within the p120ctn Arm repeat domain known to be required for
      the inhibition of RhoA is also required for binding to microtubules. We therefore
      propose that binding of p120ctn to microtubules is inversely related to its
      ability to regulate Rho GTPases.

PMID- 14660599
TI  - Tyrosine 105 and threonine 212 at outermost substrate binding subsites -6 and +4
      control substrate specificity, oligosaccharide cleavage patterns, and multiple
      binding modes of barley alpha-amylase 1.
AB  - The role in activity of outer regions in the substrate binding cleft in alpha
      amylases is illustrated by mutational analysis of Tyr(105) and Thr(212) localized
      at subsites -6 and +4 (substrate cleavage occurs between subsites -1 and +1) in
      barley alpha-amylase 1 (AMY1). Tyr(105) is conserved in plant alpha-amylases
      whereas Thr(212) varies in these and related enzymes. Compared with wild-type
      AMY1, the subsite -6 mutant Y105A has 140, 15, and <1% activity (k(cat)/K(m)) on
      starch, amylose DP17, and 2-chloro-4-nitrophenyl beta-d-maltoheptaoside, whereas
      T212Y at subsite +4 has 32, 370, and 90% activity, respectively. Thus engineering
      of aromatic stacking interactions at the ends of the 10-subsite long binding
      cleft affects activity very differently, dependent on the substrate. Y105A
      dominates in dual subsite -6/+4 [Y105A/T212(Y/W)]AMY1 mutants having almost
      retained and low activity on starch and oligosaccharides, respectively. Bond
      cleavage analysis of oligosaccharide degradation by wild-type and mutant AMY1
      supports that Tyr(105) is critical for binding at subsite -6. Substrate binding
      is improved by T212(Y/W) introduced at subsite +4 and the [Y105A/T212(Y/W)]AMY1
      double mutants synergistically enhanced productive binding of the substrate
      aglycone. The enzymatic properties of the series of AMY1 mutants suggest that
      longer substrates adopt several binding modes. This is in excellent agreement
      with computed distinct multiple docking solutions observed for maltododecaose at
      outer binding areas of AMY1 beyond subsites -3 and +3.

PMID- 14660600
TI  - Jararhagin-derived RKKH peptides induce structural changes in alpha1I domain of
      human integrin alpha1beta1.
AB  - Integrin alpha(1)beta(1) is one of four collagen-binding integrins in humans.
      Collagens bind to the alphaI domain and in the case of alpha(2)I collagen binding
      is competitively inhibited by peptides containing the RKKH sequence and derived
      from the metalloproteinase jararhagin of snake venom from Bothrops jararaca. In
      alpha(2)I, these peptides bind near the metal ion-dependent adhesion site
      (MIDAS), where a collagen (I)-like peptide is known to bind; magnesium is
      required for binding. Published structures of the ligand-bound "open"
      conformation of alpha(2)I differs significantly from the "closed" conformation
      seen in the structure of apo-alpha(2)I near MIDAS. Here we show that two
      peptides, CTRKKHDC and CARKKHDC, derived from jararhagin also bind to alpha(1)I
      and competitively inhibit collagen I binding. Furthermore, calorimetric and
      fluorimetric measurements show that the structure of the complex of alpha(1)I
      with Mg(2+) and CTRKKHDC differs from structure in the absence of peptide. A
      comparison of the x-ray structure of apo-alpha(1)I ("closed" conformation) and a
      model structure of the alpha(1)I ("open" conformation) based on the closely
      related structure of alpha(2)I reveals that the binding site is partially blocked
      to ligands by Glu(255) and Tyr(285) in the "closed" structure, whereas in the
      "open" structure helix C is unwound and these residues are shifted, and the
      "RKKH" peptides fit well when docked. The "open" conformation of alpha(2)I
      resulting from binding a collagen (I)-like peptide leads to exposure of
      hydrophobic surface, also seen in the model of alpha(1)I and shown experimentally
      for alpha(1)I using a fluorescent hydrophobic probe.

PMID- 14660601
TI  - A conserved proline in the last transmembrane segment of Gaa1 is required for
      glycosylphosphatidylinositol (GPI) recognition by GPI transamidase.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are synthesized as precursor
      proteins that are processed in the endoplasmic reticulum by GPI transamidase
      (GPIT). Human GPIT is a multisubunit membrane-bound protein complex consisting of
      Gaa1, Gpi8, phosphatidylinositol glycan (PIG)-S, PIG-T, and PIG-U. The enzyme
      recognizes a C-terminal signal sequence in the proprotein and replaces it with a
      preformed GPI lipid. The nature of the functional interaction of the GPIT
      subunits with each other and with the proprotein and GPI substrates is largely
      unknown. We recently analyzed the GPIT subunit Gaa1, a polytopic protein with
      seven transmembrane (TM) spans, to identify sequence determinants in the protein
      that are required for its interaction with other subunits and for function
      (Vainauskas, S., Maeda, Y., Kurniawan, H., Kinoshita, T., and Menon, A. K. (2002)
      J. Biol. Chem. 277, 30535-30542). We showed that elimination of the C-terminal TM
      segment of Gaa1 allows the protein to interact with Gpi8, PIG-S, and PIG-T but
      renders the resulting GPIT complex nonfunctional. We now show that GPIT complexes
      containing C-terminally truncated Gaa1 possess a full complement of subunits and
      are able to interact with a proprotein substrate but cannot co-immunoprecipitate
      GPI. We go on to show that mutation of a conserved proline residue centrally
      located within the C-terminal TM span of Gaa1 is sufficient to abrogate the
      ability of the resulting GPIT complex to co-immunoprecipitate GPI. We suggest
      that the putative dynamic hinge created by the proline residue provides a
      structural basis for the interaction of GPI with GPIT.

PMID- 14660602
TI  - Modulation of Thr phosphorylation of integrin beta1 during muscle
      differentiation.
AB  - By using transient elevations of cytosolic free calcium levels triggered by
      integrin antibody or laminin (Kwon, M. S., Park, C. S., Choi, K., Park, C.-S.,
      Ahnn, J., Kim, J. I., Eom, S. H., Kaufman, S. J., and Song, W. K. (2000) Mol.
      Biol. Cell 11, 1433-1443), we have demonstrated that protein phosphatase 2A
      (PP2A) is implicated in the regulation of reversible phosphorylation of integrin.
      In E63 skeletal myoblasts, the treatment of PP2A inhibitors such as okadaic acid
      and endothall induces an increase of phosphorylation of integrin beta1A and
      thereby inhibits integrin-induced elevation of cytosolic calcium level and
      formation of focal adhesions. None of these effects were in differentiated
      myotubes expressing the alternate beta1D isoform. In the presence of okadaic
      acid, PP2A in association with integrin beta1A was reduced on myoblasts, whereas
      beta1D on myotubes remained bound with PP2A. Both co-immunoprecipitation and in
      vitro phosphatase assays revealed that dephosphorylation of residues Thr788
      Thr789 in the integrin beta1A cytoplasmic domain is dependent upon PP2A activity.
      Mutational analysis of the cytoplasmic domain and confocal microscopy experiments
      indicated that substitution of Thr788-Thr789 with Asn788-Asn789 is of critical
      importance for regulating the function of integrin beta1. These results suggest
      that PP2A may be a primary regulator of threonine phosphorylation of integrin
      beta1A and subsequent activation of downstream signaling molecules. Taken
      together, we propose that dephosphorylation of residues Thr788-Thr789 in the
      cytoplasmic domain of integrin beta1A may contribute to the linkage of integrins
      to focal adhesion sites and induce the association with cytoskeleton proteins.
      The switch of integrin beta1A to beta1D isoform in myotubes therefore may be a
      mechanism to escape from phospho-regulation by PP2A and promotes a more stable
      association of the cytoskeleton with the extracellular matrix.

PMID- 14660603
TI  - Carboxyl methylation of Ras regulates membrane targeting and effector engagement.
AB  - Post-translational modification of Ras proteins includes prenylcysteine-directed
      carboxyl methylation. Because Ras participates in Erk activation by epidermal
      growth factor (EGF), we tested whether Ras methylation regulates Erk activation.
      EGF stimulation of Erk was inhibited by AFC (N-acetyl-S-farnesyl-L-cysteine), an
      inhibitor of methylation, but not AGC (N-acetyl-S-geranyl-L-cysteine), an
      inactive analog of AFC. AFC inhibited Ras methylation as well as the activation
      of pathway enzymes between Ras and Erk but did not inhibit EGF receptor
      phosphorylation, confirming action at the level of Ras. Transient transfection of
      human prenylcysteine-directed carboxyl methyltransferase increased EGF-stimulated
      Erk activation. AFC but not AGC inhibited movement of transiently transfected
      green fluorescent protein-Ras from the cytosol to the plasma membrane of COS-1
      cells and depleted green fluorescent protein-Ras from the plasma membrane in
      stably transfected Madin-Darby canine kidney cells, suggesting that methylation
      regulates Erk by ensuring proper membrane localization of Ras. However, when COS
      1 cells were transfected with Ras complexed to CD8, plasma membrane localization
      of Ras was unaffected by AFC, yet EGF-stimulated Erk activation was inhibited by
      AFC. Thus, Ras methylation appears to regulate Erk activation both through the
      localization of Ras as well as the propagation of Ras-dependent signals.

PMID- 14660604
TI  - Gs protein-coupled receptor agonists induce transactivation of the epidermal
      growth factor receptor in T84 cells: implications for epithelial secretory
      responses.
AB  - We have previously shown that Gq protein-coupled receptor (GqPCR) agonists
      stimulate epidermal growth factor receptor (EGFr) transactivation and activation
      of mitogen-activated protein kinases (MAPK) in colonic epithelial cells. This
      constitutes a mechanism by which Cl- secretory responses to GqPCR agonists are
      limited. In the present study we examined a possible role for the EGFr in
      regulating Cl- secretion stimulated by agonists that act through GsPCRs. All
      experiments were performed using monolayers of T84 colonic epithelial cells grown
      on permeable supports. Protein phosphorylation and protein-protein interactions
      were analyzed by immunoprecipitation and Western blotting. Cl- secretion was
      measured as changes in short-circuit current (DeltaIsc) across voltage-clamped
      T84 cells. The GsPCR agonist, vasoactive intestinal polypeptide (VIP; 100 nM),
      rapidly stimulated EGFr phosphorylation in T84 cells. This effect was mimicked by
      a cell-permeant analog of cAMP, Bt2cAMP/AM (3 microM), and was attenuated by the
      protein kinase A (PKA) inhibitor, H-89 (20 microM). The EGFr inhibitor,
      tyrphostin AG1478 (1 microM), inhibited both Bt2cAMP/AM-stimulated EGFr
      phosphorylation and Isc responses. VIP and Bt2cAMP/AM both stimulated ERK MAPK
      phosphorylation and recruitment of the p85 subunit of phosphatidylinositol 3
      kinase (PI3K) to the EGFr in a tyrphostin AG1478-sensitive manner. The PI3K
      inhibitor, wortmannin (50 nM), but not the ERK inhibitor, PD 98059 (20 microM),
      attenuated Bt2cAMP/AM-stimulated secretory responses. We conclude that GsPCR
      agonists rapidly transactivate the EGFr in T84 cells by a signaling pathway
      involving cAMP and PKA. Through a mechanism that likely involves PI3K,
      transactivation of the EGFr is required for the full expression of cAMP-dependent
      Cl- secretory responses.

PMID- 14660605
TI  - The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent
      functions in NADPH metabolism of Escherichia coli.
AB  - Pentose phosphate pathway and isocitrate dehydrogenase are generally considered
      to be the major sources of the anabolic reductant NADPH. As one of very few
      microbes, Escherichia coli contains two transhydrogenase isoforms with unknown
      physiological function that could potentially transfer electrons directly from
      NADH to NADP+ and vice versa. Using defined mutants and metabolic flux analysis,
      we identified the proton-translocating transhydrogenase PntAB as a major source
      of NADPH in E. coli. During standard aerobic batch growth on glucose, 35-45% of
      the NADPH that is required for biosynthesis was produced via PntAB, whereas
      pentose phosphate pathway and isocitrate dehydrogenase contributed 35-45% and 20
      25%, respectively. The energy-independent transhydrogenase UdhA, in contrast, was
      essential for growth under metabolic conditions with excess NADPH formation, i.e.
      growth on acetate or in a phosphoglucose isomerase mutant that catabolized
      glucose through the pentose phosphate pathway. Thus, both isoforms have divergent
      physiological functions: energy-dependent reduction of NADP+ with NADH by PntAB
      and reoxidation of NADPH by UdhA. Expression appeared to be modulated by the
      redox state of cellular metabolism, because genetic and environmental
      manipulations that increased or decreased NADPH formation down-regulated pntA or
      udhA transcription, respectively. The two transhydrogenase isoforms provide E.
      coli primary metabolism with an extraordinary flexibility to cope with varying
      catabolic and anabolic demands, which raises two general questions: why do only a
      few bacteria contain both isoforms, and how do other organisms manage NADPH
      metabolism?

PMID- 14660606
TI  - GAT (GGA and Tom1) domain responsible for ubiquitin binding and ubiquitination.
AB  - GGAs (Golgi-localizing, gamma-adaptin ear domain homology, ADP-ribosylation
      factor (ARF)-binding proteins) are a family of monomeric adaptor proteins
      involved in membrane trafficking from the trans-Golgi network to endosomes. The
      GAT (GGA and Tom1) domains of GGAs have previously been shown to interact with
      GTP-bound ARF and to be crucial for membrane recruitment of GGAs. Here we show
      that the C-terminal subdomain of the GAT domain, which is distinct from the N
      terminal GAT subdomain responsible for ARF binding, can bind ubiquitin. The
      binding is mediated by interactions between residues on one side of the alpha3
      helix of the GAT domain and those on the so-called Ile-44 surface patch of
      ubiquitin. The binding of the GAT domain to ubiquitin can be enhanced by the
      presence of a GTP-bound form of ARF. Furthermore, GGA itself is ubiquitinated in
      a manner dependent on the GAT-ubiquitin interaction. These results delineate the
      molecular basis for the interaction between ubiquitin and GAT and suggest that
      GGA-mediated trafficking is regulated by the ubiquitin system as endosomal
      trafficking mediated by other ubiquitin-binding proteins.

PMID- 14660607
TI  - Caveolin-1 knockdown by small interfering RNA suppresses responses to the
      chemokine monocyte chemoattractant protein-1 by human astrocytes.
AB  - Astrocytes regulate the integrity of the blood-brain barrier and influence
      inflammatory processes in the central nervous system. The pro-inflammatory
      chemokine monocyte chemoattractant protein-1 (MCP-1), which is both released by
      and stimulates astrocytes, is thought to play a crucial role in both these
      activities. Because astrocytes have been shown to possess caveolae, vesicular
      structures that participate in intracellular transport and signal transduction
      events, we reasoned that expression of the major structural protein of these
      organelles, caveolin-1, might feature critically in the cellular responses to MCP
      1. To test this hypothesis, caveolin-1 level was "knocked down" in human
      astrocyte cultures by using a small interfering RNA approach. This method
      resulted in efficient (>90% loss) and specific knockdown of caveolin-1 expression
      while sparring glial fibrillary acidic protein as well as several other proteins
      involved in endocytosis. Astrocytes suffering caveolin-1 loss showed diminished
      ability to down-modulate and internalize the MCP-1 receptor (CCR2) in response to
      exposure to this chemokine and also demonstrated significantly reduced capacity
      to undergo chemotaxis and calcium flux when MCP-1-stimulated. The results
      highlight a potentially prominent role for caveolae and/or caveolin-1 in
      mediating astrocyte responses to MCP-1, a feature that might significantly
      dictate the progression of inflammatory events at the blood-brain barrier.

PMID- 14660608
TI  - MDM4 (MDMX) overexpression enhances stabilization of stress-induced p53 and
      promotes apoptosis.
AB  - Rescue of embryonic lethality in MDM4(-/-) mice through concomitant loss of p53
      has revealed a functional partnership between the two proteins. Biochemical
      studies have suggested that MDM4 may act as a negative regulator of p53 levels
      and activity. On the other hand, MDM4 overexpression has been reported to
      stabilize p53 levels and to counteract MDM2-degradative activity. We have
      investigated the functional role of MDM4 overexpression on cell behavior. In both
      established and primary cells cultured under stress conditions, overexpression of
      MDM4 significantly increased p53-dependent cell death, in correlation with
      enhanced induction of the endogenous p53 protein levels. This phenomenon was
      associated with induced p53 transcriptional activity and increased levels of the
      proapoptotic protein, Bax. Further, p53 stabilization was accompanied by
      decreased association of the protein to its negative regulator, MDM2. These
      findings reveal a novel role for MDM4 by demonstrating that in non-tumor cells
      under stress conditions it may act as a positive regulator of p53 activity,
      mainly by controlling p53 levels. They also indicate a major distinction between
      the biological consequences of MDM4 and MDM2 overexpression.

PMID- 14660609
TI  - Origin and mechanisms of Ca2+ waves in smooth muscle as revealed by localized
      photolysis of caged inositol 1,4,5-trisphosphate.
AB  - The cytosolic Ca(2+) concentration ([Ca(2+)](c)) controls diverse cellular events
      via various Ca(2+) signaling patterns; the latter are influenced by the method of
      cell activation. Here, in single-voltage clamped smooth muscle cells, sarcolemma
      depolarization generated uniform increases in [Ca(2+)](c) throughout the cell
      entirely by Ca(2+) influx. On the other hand, the Ca(2+) signal produced by
      InsP(3)-generating agonists was a propagated wave. Using localized uncaged
      InsP(3), the forward movement of the Ca(2+) wave arose from Ca(2+)-induced Ca(2+)
      release at the InsP(3) receptor (InsP(3)R) without ryanodine receptor
      involvement. The decline in [Ca(2+)](c) (the back of the wave) occurred from a
      functional compartmentalization of the store, which rendered the site of InsP(3)
      mediated Ca(2+) release, and only this site, refractory to the phosphoinositide.
      The functional compartmentalization arose by a localized feedback deactivation of
      InsP(3) receptors produced by an increased [Ca(2+)](c) rather than a reduced
      luminal [Ca(2+)] or an increased cytoplasmic [InsP(3)]. The deactivation of the
      InsP(3) receptor was delayed in onset, compared with the time of the rise in
      [Ca(2+)](c), persisted (>30 s) even when [Ca(2+)](c) had regained resting levels,
      and was not prevented by kinase or phosphatase inhibitors. Thus different forms
      of cell activation generate distinct Ca(2+) signaling patterns in smooth muscle.
      Sarcolemma Ca(2+) entry increases [Ca(2+)](c) uniformly; agonists activate
      InsP(3)R and produce Ca(2+) waves. Waves progress by Ca(2+)-induced Ca(2+)
      release at InsP(3)R, and persistent Ca(2+)-dependent inhibition of InsP(3)R
      accounts for the decline in [Ca(2+)](c) at the back of the wave.

PMID- 14660610
TI  - CYP2U1, a novel human thymus- and brain-specific cytochrome P450, catalyzes omega
      and (omega-1)-hydroxylation of fatty acids.
AB  - Long chain fatty acids have recently emerged as critical signaling molecules in
      neuronal, cardiovascular, and renal processes, yet little is presently known
      about the precise mechanisms controlling their tissue distribution and
      bioactivation. We have identified a novel cytochrome P450, CYP2U1, which may play
      an important role in modulating the arachidonic acid signaling pathway. Northern
      blot and real-time PCR analysis demonstrated that CYP2U1 transcripts were most
      abundant in the thymus and the brain (cerebellum), indicating a specific
      physiological role for CYP2U1 in these tissues. Recombinant human CYP2U1 protein,
      expressed in baculovirus-infected Sf9 insect cells, was found to metabolize
      arachidonic acid exclusively to two region-specific products as determined by
      liquid chromatography-mass spectrometry. These metabolites were identified as 19-
      and 20-hydroxy-modified arachidonic acids by liquid chromatography-tandem mass
      spectrometry analysis. In addition to omega/omega-1 hydroxylation of arachidonic
      acid, CYP2U1 protein also catalyzed the hydroxylation of structurally related
      long chain fatty acid (docosahexaenoic acid) but not fatty acids such as lauric
      acid or linoleic acid. This is the first report of the cloning and functional
      expression of a new human member of P450 family 2, CYP2U1, which metabolizes long
      chain fatty acids. Based on the ability of CYP2U1 to generate bioactive
      eicosanoid derivatives, we postulate that CYP2U1 plays an important physiological
      role in fatty acid signaling processes in both cerebellum and thymus.

PMID- 14660611
TI  - A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding
      affinity to protein kinase C.
AB  - Dilated cardiomyopathy is characterized by ventricular dilation with systolic
      dysfunction of cardiac muscle. Recent genetic studies have revealed that
      mutations in genes for cytoskeleton proteins distributed in the Z-disc and/or
      intercalated discs of the cardiac muscle are major predictors of cardiomyopathy.
      However, as mutations in these genes can account for only a part of the patient
      population, there should be another disease-causing gene(s) for cardiomyopathy.
      Cypher/ZASP appears to be an ideal candidate for the cardiomyopathy causative
      gene, because Cypher/ZASP encodes a Z-disc associated protein, and recent studies
      have demonstrated that Cypher/ZASP knock-out mice develop cardiomyopathy. In this
      study, we searched for sequence variations in Cypher/ZASP in 96 unrelated
      Japanese patients with dilated cardiomyopathy. A D626N mutation located within
      the third LIM domain was identified in a familial case but not found in the
      unrelated controls. A family study of the patient showed that all affected
      siblings tested had the same mutation. Clinical information of the affected
      family members suggested that the mutation was associated with late onset
      cardiomyopathy. To reveal the biochemical changes due to the mutation, we
      performed a yeast two-hybrid assay and a pull-down assay. It was demonstrated by
      both assays that the D626N mutation of Cypher/ZASP increased the affinity of the
      LIM domain for protein kinase C, suggesting a novel biochemical mechanism of the
      pathogenesis of dilated cardiomyopathy.

PMID- 14660612
TI  - Structural insights into the interaction of ROCKI with the switch regions of
      RhoA.
AB  - The Rho-ROCK pathway modulates the phosphorylation level of a variety of
      important signaling proteins and is thereby involved in miscellaneous cellular
      processes including cell migration, neurite outgrowth, and smooth muscle
      contraction. The observation of the involvement of the Rho-ROCK pathway in tumor
      invasion and in diseases such as hypertension and bronchial asthma makes it an
      interesting target for drug development. We herein present the crystal structure
      of the complex between active RhoA and the Rho-binding domain of ROCKI. The Rho
      binding domain structure forms a parallel alpha-helical coiled-coil dimer and, in
      contrast to the published Rho-protein kinase N structure, binds exclusively to
      the switch I and II regions of the guanosine 5'-(beta,gamma-imido)triphosphate
      bound RhoA. The switch regions of two different RhoA molecules form a
      predominantly hydrophobic patch, which is complementarily bound by two identical
      short helices of 13 residues (amino acids 998-1010). The identified ROCK-binding
      site of RhoA strikingly supports the assumption of a common consensus-binding
      site for effector recognition.

PMID- 14660613
TI  - The role of Pre-H2 domains of alpha- and delta-epithelial Na+ channels in ion
      permeation, conductance, and amiloride sensitivity.
AB  - Epithelial Na(+) channels (ENaC) regulate salt and water re-absorption across the
      apical membrane of absorptive epithelia such as the kidney, colon, and lung.
      Structure-function studies have suggested that the second transmembrane domain
      (M2) and the adjacent pre- and post-M2 regions are involved in channel pore
      formation, cation selectivity, and amiloride sensitivity. Because Na(+)
      selectivity, unitary Na(+) conductance (gamma(Na)), and amiloride sensitivity of
      delta-ENaC are strikingly different from those of alpha-ENaC, the hypothesis that
      the pre-H2 domain may contribute to these characterizations has been examined by
      swapping the pre-H2, H2, and both (pre-H2+H2) domains of delta- and alpha-ENaCs.
      Whole-cell and single channel results showed that the permeation ratio of Li(+)
      and Na(+) (P(Li)/P(Na)) for the swap alpha chimeras co-expressed with betagamma
      ENaC in Xenopus oocytes decreased significantly. In contrast, the ratio of
      P(Li)/P(Na) for the swap delta constructs was not significantly altered. Single
      channel studies confirmed that swapping of the H2 and the pre-H2+H2 domains
      increased the gamma(Na) of alpha-ENaC but decreased the gamma(Na) of delta-ENaC.
      A significant increment in the apparent inhibitory dissociation constant for
      amiloride (K(i)(amil)) was observed in the alpha chimeras by swapping the pre-H2,
      H2, and pre-H2+H2 domains. In contrast, a striking decline of K(i)(amil) was
      obtained in the chimeric delta constructs with substitution of the H2 and pre
      H2+H2 domains. Our results demonstrate that the pre-H2 domain, combined with the
      H2 domain, contributes to the P(Li)/P(Na) ratio, single channel Na(+)
      conductance, and amiloride sensitivity of alpha- and delta-ENaCs.

PMID- 14660614
TI  - The 31-kDa caspase-generated cleavage product of p130cas functions as a
      transcriptional repressor of E2A in apoptotic cells.
AB  - In response to integrin receptor binding to the extracellular matrix, the
      multidomain docking protein p130(cas) (Crk-associated substrate) activates
      various signaling cascades modulating such cellular processes as proliferation,
      migration, and apoptosis. During apoptosis, caspase-mediated cleavage of
      p130(cas) generated a C-terminal 31-kDa fragment (31-kDa) and promoted
      morphological changes characteristic of apoptosis, including loss of focal
      adhesions, cell rounding, and nuclear condensation and fragmentation. By
      contrast, a p130(cas) D748E mutant, which was unable to produce 31-kDa,
      attenuated the disassembly of focal adhesions at the bottom of the cell. 31-kDa
      contains a helix-loop-helix (HLH) domain that shows greater sequence homology
      with Id proteins than with basic HLH proteins, which enabled heterodimerization
      with E2A. Once coupled to E2A, 31-kDa was translocated to the cell nucleus, where
      it inhibited E2A-mediated p21(Waf1/Cip1) transcription. Moreover, overexpression
      of 31-kDa led to cell death that could be inhibited by treatment with the caspase
      inhibitor ZVAD-fluoromethyl ketone or by ectopic expression of E2A or
      p21(Waf1/Cip1). These data suggest that during etoposide-induced apoptosis, 31
      kDa promotes caspase-mediated cell death by inhibiting E2A-mediated activation of
      p21(Waf1/Cip1) transcription.

PMID- 14660615
TI  - High order quaternary arrangement confers increased structural stability to
      Brucella sp. lumazine synthase.
AB  - The penultimate step in the pathway of riboflavin biosynthesis is catalyzed by
      the enzyme lumazine synthase (LS). One of the most distinctive characteristics of
      this enzyme is the structural quaternary divergence found in different species.
      The protein exists as pentameric and icosahedral forms, built from practically
      the same structural monomeric unit. The pentameric structure is formed by five 18
      kDa monomers, each extensively contacting neighboring monomers. The icosahedrical
      structure consists of 60 LS monomers arranged as 12 pentamers giving rise to a
      capsid exhibiting icosahedral 532 symmetry. In all lumazine synthases studied,
      the topologically equivalent active sites are located at the interfaces between
      adjacent subunits in the pentameric modules. The Brucella sp. lumazine synthase
      (BLS) sequence clearly diverges from pentameric and icosahedric enzymes. This
      unusual divergence prompted us to further investigate its quaternary arrangement.
      In the present work, we demonstrate by means of solution light scattering and x
      ray structural analyses that BLS assembles as a very stable dimer of pentamers,
      representing a third category of quaternary assembly for lumazine synthases. We
      also describe by spectroscopic studies the thermodynamic stability of this
      oligomeric protein and postulate a mechanism for dissociation/unfolding of this
      macromolecular assembly. The higher molecular order of BLS increases its
      stability 20 degrees C compared with pentameric lumazine synthases. The decameric
      arrangement described in this work highlights the importance of quaternary
      interactions in the stabilization of proteins.

PMID- 14660616
TI  - Role of the 3'-untranslated region of human endothelin-1 in vascular endothelial
      cells. Contribution to transcript lability and the cellular heat shock response.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide expressed in the vascular
      endothelium. Stringent control over ET-1 expression is achieved through a highly
      regulated promoter and rapid mRNA turnover. Since little is known about
      mechanisms governing ET-1 post-transcriptional regulation, and changes in ET-1
      mRNA stability are implicated in disease processes, we characterized these
      pathways using a variety of functional approaches. We expressed human ET-1 and
      luciferase transcripts with or without a wild type ET-1 3'-untranslated region
      (3'-UTR) and found that the 3'-UTR had potent mRNA destabilizing activity.
      Deletion analysis localized this activity to two domains of the 3'-UTR we have
      termed destabilizing elements 1 and 2 (DE1 and DE2). Mutational studies revealed
      that DE1 functions as an AU-rich element (ARE) dependent on a 100-nucleotide
      region. This activity was further localized to a 10-nucleotide region at position
      978-987 of the 3'-UTR. Depletion of AUF1 by RNA interference up-regulated ET-1 in
      endothelial cells suggesting AUF1-dependent regulation. Since AUF1 functions
      through the ubiquitin-proteasome pathway, we disrupted this pathway with heat
      shock and proteasome inhibitor in endothelial cells and observed stabilization of
      endogenous ET-1 mRNA. Chimeric transcripts bearing wild type ET-1 3'-UTRs were
      also stabilized in response to proteasome inhibition whereas DE1 mutants failed
      to respond. Taken together, these findings suggest a complex model of ARE
      mediated mRNA turnover dependent on two 3'-UTR domains, DE1 and DE2. Furthermore,
      DE1 functions as an ARE directing mRNA half-life through the proteasome. Finally,
      this data provides evidence for a novel pathway of ET-1 mRNA stabilization by
      heat shock.

PMID- 14660617
TI  - Ectodomains 3 and 4 of human polymeric Immunoglobulin receptor (hpIgR) mediate
      invasion of Streptococcus pneumoniae into the epithelium.
AB  - Streptococcus pneumoniae binds to the ectodomain of the human polymeric Ig
      receptor (pIgR), also known as secretory component (SC), via a hexapeptide motif
      in the choline-binding protein SpsA. The SpsA-pIgR interaction mediates adherence
      and internalization of the human pathogen into epithelial cells. In this study
      the results of SpsA binding to human, mouse, and chimeric SC strongly supported
      the human specificity of this unique interaction and suggested that binding sites
      in the third and fourth Ig-like domain of human SC (D3 and D4, respectively) are
      involved in SpsA-pIgR complex formation. Binding of SpsA to SC-derived synthetic
      peptides indicated surface-located potential binding motifs in D3 and D4.
      Adherence and uptake of pneumococci or SpsA-coated latex beads depended on the
      SpsA hexapeptide motif as well as SpsA-binding sites in D3 and D4 of human pIgR.
      The involvement of D3 and D4 in adherence and invasion was demonstrated by the
      lack of binding of SpsA-coated latex beads to transfected epithelial cells
      expressing mutated pIgR. Finally, blocking experiments with chimeric human-mouse
      SC as well as synthetic peptides indicated the participation of D3 and a key role
      of D4 in pneumococcal invasion.

PMID- 14660618
TI  - The mitotic chromosome is an assembly of rigid elastic axes organized by
      structural maintenance of chromosomes (SMC) proteins and surrounded by a soft
      chromatin envelope.
AB  - The structure of mitotic chromosomes is still poorly understood. Here we describe
      the use of a novel approach based on elasticity measurements of a single
      chromosome for studying the organization of these objects. The data reveal that
      mitotic chromosomes exhibit a non-homogenous structure consisting of rigid
      elastic axes surrounded by a soft chromatin envelope. The chemical continuity of
      DNA, but not RNA, was required for the maintenance of these axes. The axes show a
      modular structure, and the structural maintenance of chromosomes (SMC) proteins
      participate in their organization. Topoisomerase II was not involved in either
      the organization of the axes or the maintenance of the mitotic chromosomes. A
      model for the assembly and the structure of the mitotic chromosome is proposed.
      According this model, the chromosome axes are dynamic structures that assemble at
      the onset and disassemble the end of mitosis, respectively. The SMC proteins, in
      addition to maintaining axis elasticity, are essential for the determination of
      the rod-like chromosome shape. The extreme compaction of mitotic chromosomes is
      determined mainly by the high amount of bivalent ions bound to DNA at mitosis.

PMID- 14660619
TI  - An autocrine/paracrine loop linking keratin 14 aggregates to tumor necrosis
      factor alpha-mediated cytotoxicity in a keratinocyte model of epidermolysis
      bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is a blistering cutaneous disease featuring
      protein aggregates. Here we investigate the molecular mechanisms linking protein
      aggregates to cell death in a cellular model of EBS in which HaCaT keratinocytes
      are transfected with plasmids expressing various mutant forms of keratin 14
      (K14). In HaCaT cells, mutant K14 was found to form ubiquitinated protein
      aggregates that suppressed 20 S proteasome function instead of being degraded by
      20 S proteasome. Keratinocytes with mutant K14-induced phosphorylation of the
      stress-activated kinase c-Jun, as well as up-regulation of unfolding protein Bip,
      indicates induction of endoplasmic reticulum stress. HaCaT cells were susceptible
      to apoptosis by activation of caspases-3, and -8, but not caspase-9 or -12. Tumor
      necrosis factor-alpha (TNFalpha) in the culture medium was increased in
      keratinocytes with mutant K14 compared with wild K14, and the addition of
      neutralizing anti-TNFalpha antibody to the culture medium rescued keratinocytes
      from cell death. Thus, TNFalpha release and the subsequent activation of the
      TNFalpha receptor by an autocrine/paracrine pathway links protein aggregates to
      cell death in this keratinocyte EBS cellular model. Furthermore, mutation in K14
      reduced its affinity to TNFalpha receptor-associated death domain (TRADD),
      suggesting that the susceptibility of keratinocytes to caspase-8-mediated
      apoptosis is increased in mutated K14 because of impairment of the cytoprotective
      mechanism mediated by K14-TRADD interaction.

PMID- 14660620
TI  - Distinctive expression patterns of heparan sulfate O-sulfotransferases and
      regional differences in heparan sulfate structure in chick limb buds.
AB  - The skeletal tissue development and patterning in chick limb buds are known to be
      under the spacio-temporal control of various heparin-binding cell growth factors
      such as fibroblast growth factors and bone morphogenetic proteins. Different
      structural regions on heparan sulfate (HS) chains of proteoglycans could be
      implicated in regional differences in the binding capacities of these cell growth
      factors, by which they could selectively interact with targeted cells and
      regulate their signaling in those processes. In this study we first demonstrated
      by cDNA cloning that one heparan sulfate 2-O-sulfotransferase (HS2ST) and two
      isoforms of heparan sulfate 6-O-sulfotransferase (HS6ST-1 and -2) occurred in
      chick embryos and had different substrate specificities each other. We next
      showed by whole mount in situ hybridization that the HS6ST-1 and HS6ST-2
      transcripts were preferentially localized to the anterior proximal region and at
      the posterior proximal region of the limb bud, respectively, whereas the HS2ST
      transcript was distributed rather uniformly throughout the bud. Analyses of the
      structures of HS from different regions of the wing buds have shown variation in
      that 6-O-sulfated residues are more abundant in the proximal than distal region,
      whereas iduronosyl 6-O-sulfated residues are abundant in the anterior proximal
      region and glucuronosyl 6-O-sulfated residues in the posterior proximal region.
      These results suggest that HS with different sulfation patterns created with
      multiple sulfotransferase activities provides an appropriate extracellular
      environment for morphogenetic signal transduction.

PMID- 14660621
TI  - Mechanosensitivity of GIRK channels is mediated by protein kinase C-dependent
      channel-phosphatidylinositol 4,5-bisphosphate interaction.
AB  - Gprotein-activated inwardly rectifying K+ channel (GIRK or Kir3) currents are
      inhibited by mechanical stretch of the cell membrane, but the underlying
      mechanisms are not understood. In Xenopus oocytes heterologously expressing GIRK
      channels, membrane stretch induced by 50% reduction of osmotic pressure caused a
      prompt reduction of GIRK1/4, GIRK1, and GIRK4 currents by 16.6-42.6%. Comparable
      GIRK current reduction was produced by protein kinase C (PKC) activation (phorbol
      12-myristate 13-acetate). The mechanosensitivity of the GIRK4 current was
      abolished by pretreatment with PKC inhibitors (staurosporine or calphostin C).
      Neither hypo-osmotic challenge nor PKC activation affected IRK1 currents. GIRK4
      chimera (GIRK4-IRK1-(Lys207-Leu245)) and single point mutant (GIRK4(I229L)), in
      which the phosphatidylinositol 4,5-bisphosphate (PIP2) binding domain or residue
      was replaced by the corresponding region of IRK1 to strengthen the channel-PIP2
      interaction, showed no mechanosensitivity and minimal PKC sensitivity. IRK1
      gained mechanosensitivity and PKC sensitivity by reverse double point mutation of
      the PIP2 binding domain (L222I/R213Q). Overexpression of Gbetagamma, which is
      known to strengthen the channel-PIP2 interaction, attenuated the
      mechanosensitivity of GIRK4 channels. In oocytes expressing a pleckstrin homology
      domain of PLC-delta tagged with green fluorescent protein, hypo-osmotic challenge
      or PKC activation caused a translocation of the fluorescence signal from the cell
      membrane to the cytosol, reflecting PIP2 hydrolysis. The translocation was
      prevented by pretreatment with PKC inhibitors. Involvement of PKC activation in
      the mechanosensitivity of muscarinic K+ channels was confirmed in native rabbit
      atrial myocytes. These results suggest that the mechanosensitivity of GIRK
      channels is mediated primarily by channel-PIP2 interaction, with PKC playing an
      important role in modulating the interaction probably through PIP2 hydrolysis.

PMID- 14660622
TI  - Generation and characterization of a highly stable form of activated thrombin
      activable fibrinolysis inhibitor.
AB  - Activated thrombin-activable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase
      B that can down-regulate fibrinolysis. TAFIa is a labile enzyme that can be
      inactivated by conformational instability or proteolysis. TAFI is approximately
      40% identical to pancreatic carboxypeptidase B (CPB). In contrast to TAFIa,
      pancreatic CPB is a stable protease. We hypothesized that regions or residues
      that are not conserved in TAFIa compared with pancreatic CPB play a role in the
      conformational instability of TAFIa and that replacement of these non-conserved
      residues with residues of pancreatic CPB would lead to a TAFIa molecule with an
      increased stability. Therefore, we have expressed, purified, and characterized
      two TAFI-CPB chimeras: TAFI-CPB-(293-333) and TAFI-CPB-(293-401). TAFI-CPB-(293
      333) could be activated by thrombin-thrombomodulin, but not as efficiently as
      wild-type TAFI. After activation, this mutant was unstable and was hardly able to
      prolong clot lysis of TAFI-deficient plasma. Binding of TAFI-CPB-(293-333) to
      both plasminogen and fibrinogen was normal compared with wild-type TAFI. TAFI-CPB
      (293-401) could be activated by thrombin-thrombomodulin, although at a lower rate
      compared with wild-type TAFI. The activated mutant displayed a markedly prolonged
      half-life of 1.5 h. Plasmin could both activate and inactivate this chimera.
      Interestingly, this chimera did not bind to plasminogen or fibrinogen. TAFI-CPB
      (293-401) could prolong the clot lysis time in TAFI-deficient plasma, although
      not as efficiently as wild-type TAFI. In conclusion, by replacing a region in
      TAFI with the corresponding region in pancreatic CPB, we were able to generate a
      TAFIa form with a highly stable activity.

PMID- 14660623
TI  - In vitro disassembly of a parvovirus capsid and effect on capsid stability of
      heterologous peptide insertions in surface loops.
AB  - We have analyzed the in vitro disassembly of the capsid of the minute virus of
      mice, and the stability of capsid chimeras carrying heterologous epitope
      insertions. Upon heating in a physiological buffer, empty capsids formed by 60
      copies of protein VP2 underwent first a reversible conformational change with a
      small enthalpy change detected by fluorescence. This change was associated with,
      but not limited to, externalization of the VP2 N terminus. Irreversible capsid
      dissociation as detected by changes in fluorescence, hemagglutination activity,
      and electrophoretic mobility occurred at much higher temperatures. Differential
      scanning calorimetry in the same conditions indicated that the
      dissociation/denaturation transition involved a high enthalpy change and
      proceeded through one or more intermediates. In contrast, in the presence of 1.5
      M guanidinium chloride, heat-induced disassembly fitted a two-state irreversible
      process. Both thermally and chemically induced dissociation/denaturation yielded
      a form that had lost a part of the tertiary structure, but still retained the
      native secondary structure. Data from chemical dissociation indicates this form
      may correspond to a molten globule-like monomeric state of the capsid protein.
      All five antigenic peptide insertions attempted in exposed loops, despite being
      perhaps among the least disruptive, led to defects in folding/assembly of the
      capsid and, in most cases, to reduced capsid stability against thermal
      dissociation. The results with one of the simplest viral capsids reveal a complex
      pathway for disassembly, and a reduction in capsid assembly and stability upon
      insertion of peptides, even within the most exposed capsid loops.

PMID- 14660624
TI  - Evidence of a transcriptional co-activator function of cohesin STAG/SA/Scc3.
AB  - Cohesins hold sister chromatids together from DNA replication until they are
      segregated. Although cohesins Smc1, Smc3, and Scc1/Rad21 are involved in
      chromatid cohesion and other cellular processes, little is known about the other
      mitotic cohesin subunit, Scc3/STAG. Here we describe STAG/Scc3, which may act as
      a transcriptional co-activator. STAG2 is able to enhance the activity of the
      tumor necrosis factor alpha, the CD69, and the human immunodeficiency virus long
      terminal repeat promoters in a NF-kappaB-dependent manner. In addition, STAG2
      interacts with the viral transactivator Tat and enhances the Tat-mediated
      activation of the human immunodeficiency virus long terminal repeat promoter.
      Moreover, STAG2 co-activates a multimeric NF-kappaB reporter construct and
      enhances the activity of the transactivation domain of p65/RelA in a Gal4 system.
      This function is dependent on one of the LXXLL co-activation motives present in
      this cohesin and is substantiated by the interaction of STAG2 with the p65
      subunit of NF-kappaB. These results describe a novel activity for cohesins,
      suggesting a role for STAG/Scc3 in transcriptional regulation.

PMID- 14660625
TI  - Resistance of mitochondrial DNA-depleted cells against cell death: role of
      mitochondrial superoxide dismutase.
AB  - We have shown that mitochondrial DNA-depleted (rho(0)) SK-Hep1 hepatoma cells are
      resistant to apoptosis, contrary to previous papers reporting normal apoptotic
      susceptibility of rho(0) cells. We studied the changes of gene expression in SK
      Hep1 rho(0) cells. DNA chip analysis showed that MnSOD expression was profoundly
      increased in rho(0) cells. O(2)(.) contents increased during rho(0) cell
      derivation but became normalized after establishment of rho(0) phenotypes,
      suggesting that MnSOD induction is an adaptive process to increased O(2)(.).
      rho(0) cells were resistant to menadione, paraquat, or doxorubicin, and O(2)(.)
      contents after treatment with them were lower in rho(0) cells compared with
      parental cells because of MnSOD overexpression. Expression levels and activity of
      glutathione peroxidases were also increased in rho(0) cells, rendering them
      resistant to exogenous H(2)O(2). rho(0) cells were resistant to p53, and
      intracellular ROS contents after p53 expression were lower compared with parental
      cells. Other types of rho(0) cells also showed increased MnSOD expression and
      resistance against ROS. Heme oxygenase-1 expression was increased in rho(0)
      cells, and a heme oxygenase-1 inhibitor decreased the induction of MnSOD in
      rho(0) cells and their resistance against ROS donors. These results indicate that
      rho(0) cells are resistant to cell death contrary to previous reports and suggest
      that an adaptive increase in the expression of antioxidant enzymes renders cancer
      cells or aged cells with frequent mitochondrial DNA mutations to resist against
      oxidative stress, host anti-cancer surveillance, or chemotherapeutic agents,
      conferring survival advantage on them.

PMID- 14660626
TI  - Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal
      tyrosine sulfate-rich region by proteolysis at a site that is sensitive to matrix
      metalloproteinase-13.
AB  - Integrity of cartilage fails in joint disease. The current work aimed to identify
      candidate active proteinases in joint diseases using an in vitro model for
      cartilage degradation induced by interleukin-1. A critical event in the process
      of cartilage destruction in joint disease is the failure of the collagen fiber
      network to maintain integrity. Proteins binding to the surface of the fibers are
      likely early points of failure. Fibromodulin, a member of the leucine-rich repeat
      protein family, is one predominant protein in cartilage and is known for its
      roles in the formation of collagen fibrils and sustained interaction with these
      formed fibers. Cleavage removes the tyrosine sulfate-rich region in the N
      terminus of fibromodulin. Whereas fibromodulin bound to collagen in tissue was
      digested, purified fibromodulin was not cleaved. In contrast an N-terminal 10-kDa
      fragment, Gln19-Lys98, of the protein generated by Lys-C digestion contains the
      cleavage site and was a substrate cleaved by the enzyme in medium from stimulated
      cultures. In solution, digestion of this substrate with matrix metalloproteinase
      (MMP)-2, -9, -8, and -13 demonstrated that only MMP-13 was capable to efficiently
      cleave it. The cleavage product obtained after MMP-13 digestion was identical to
      that observed in cleaved fibromodulin from cartilage explant cultures stimulated
      with interleukin-1. MMP-13 treatment of fresh articular cartilage also produced
      the fragment under study. The elucidation of the enzyme responsible for such
      cleavage may lead to treatment modalities involving its selective inhibition for
      patients suffering from arthritis. The known structure of the fragments permits
      the generation of neo-epitope antibodies to the cleavage site, which can be used
      to detect ongoing cartilage degradation in patients with arthritic disease, an
      important adjunct in monitoring disease progression, active disease, and efficacy
      of treatment.

PMID- 14660627
TI  - Cross-talk and co-trafficking between rho1/GABA receptors and ATP-gated channels.
AB  - Gamma-aminobutyric-acid (GABA) and ATP ionotropic receptors represent two
      structurally and functionally different classes of neurotransmitter-gated
      channels involved in fast synaptic transmission. We demonstrate here that, when
      the inhibitory rho1/GABA and the excitatory P2X2 receptor channels are co
      expressed in Xenopus oocytes, activation of one channel reduces the currents
      mediated by the other one. This reciprocal inhibitory cross-talk is a receptor
      mediated phenomenon independent of agonist cross-modulation, membrane potential,
      direction of ionic flux, or channel densities. Functional interaction is
      disrupted when the cytoplasmic C-terminal domain of P2X2 is deleted or in
      competition experiments with minigenes coding for the C-terminal domain of P2X2
      or the main intracellular loop of rho1 subunits. We also show a physical
      interaction between P2X2 and rho1 receptors expressed in oocytes and the co
      clustering of these receptors in transfected hippocampal neurons. Co-expression
      with P2X2 induces retargeting and recruitment of mainly intracellular rho1/GABA
      receptors to surface clusters. Therefore, molecular and functional cross-talk
      between inhibitory and excitatory ligand-gated channels may regulate synaptic
      strength both by activity-dependent current occlusion and synaptic receptors co
      trafficking.

PMID- 14660628
TI  - Chronic high glucose lowers pyruvate dehydrogenase activity in islets through
      enhanced production of long chain acyl-CoA: prevention of impaired glucose
      oxidation by enhanced pyruvate recycling through the malate-pyruvate shuttle.
AB  - In islet beta-cells, the high expression of pyruvate carboxylase and the
      functional importance of the downstream anaplerosis pathways result in a unique
      characteristic whereby high glucose and fatty acids both increase production of a
      key fatty acid metabolite, long chain acyl-CoA, for signaling and enzyme
      regulation in beta-cells. We showed previously in islets that pyruvate
      dehydrogenase (PDH) activity is lowered by excess fatty acids (the so-called
      Randle effect). We have now investigated PDH activity and pyruvate metabolism in
      islets after 48-h culture at 16.7 mmol/liter glucose. Active PDH V(max) was
      lowered 65% by 48 h of high glucose, and this effect was markedly attenuated by
      co-culture with triacsin C, which inhibits acyl-CoA synthase. Despite the large
      reduction in PDH activity, glucose oxidation was twice normal. The reason was
      continued metabolism of pyruvate through pyruvate carboxylase (V(max), 83% of
      control) and diversion of flux through the pyruvate-malate shuttle. The result
      was a 3-fold increase of the pyruvate concentration that overcame the lowered PDH
      activity by mass action as shown by glucose oxidation measured with [6
      (14)C]glucose being twice normal. In addition, glucose-induced insulin secretion
      was 3-fold increased after 48 h of high glucose, and this effect was totally
      blocked by co-culture with triacsin C. These results show that a unique feature
      of islet beta-cells is not only fatty acids but also excess glucose that impairs
      PDH activity. Also, a specialized trait of beta-cells is a long chain acyl-CoA
      mediated defense mechanism that prevents a reduction in glucose oxidation and
      consequently in insulin secretion.

PMID- 14660629
TI  - Regulatory interaction between arylhydrocarbon receptor and SIM1, two basic helix
      loop-helix PAS proteins involved in the control of food intake.
AB  - The basic helix-loop-helix PAS (bHLH-PAS) transcription factors SIM1 and
      arylhydrocarbon receptor (AHR) are involved in the control of feeding behavior.
      Sim1 haploinsufficiency causes hyperphagia in mice and humans, most likely by
      perturbing the hypothalamus function. The administration of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AHR, causes severe anorexia,
      which also appears to be of central origin. Both SIM1 and AHR require
      heterodimerization either with ARNT or ARNT2 to function. Here, we characterize
      the promoter for Sim1 and show that a consensus AHR-ARNT/2 binding site
      positively regulates its activity in the context of transfection experiments in
      Neuro-2A cells. A gel shift assay indicated that AHR-ARNT/2 can bind its putative
      site in the Sim1 promoter. Overexpression of Arnt, Arnt2, or Ahr increased the
      activity of a reporter construct containing the Sim1 promoter by 1.8-, 1.5-, and
      2.2-fold, respectively, but failed to do so when the AHR-ARNT/2 binding site was
      mutated. Similarly, TCDD increased the activity of the reporter construct by 1.8
      fold but not that of its mutated version. Finally, we found that TCDD increased
      Sim1 expression in Neuro-2A cells and in mouse kidney and hypothalamus by 4-, 3-,
      and 2-fold, respectively. We conclude that Sim1 expression is regulated by AHR
      ARNT/2. This result raises the possibility that Sim1 mediates the effect of TCDD
      on feeding and points to a complex network of regulatory interactions between
      bHLH-PAS proteins.

PMID- 14660630
TI  - Lysophosphatidic acid (LPA) in malignant ascites stimulates motility of human
      pancreatic cancer cells through LPA1.
AB  - Cytokines and growth factors in malignant ascites are thought to modulate a
      variety of cellular activities of cancer cells and normal host cells. The
      motility of cancer cells is an especially important activity for invasion and
      metastasis. Here, we examined the components in ascites, which are responsible
      for cell motility, from patients and cancer cell-injected mice. Ascites
      remarkably stimulated the migration of pancreatic cancer cells. This response was
      inhibited or abolished by pertussis toxin, monoglyceride lipase, an enzyme
      hydrolyzing lysophosphatidic acid (LPA), and Ki16425 and VPC12249, antagonists
      for LPA receptors (LPA1 and LPA3), but not by an LPA3-selective antagonist. These
      agents also inhibited the response to LPA but not to the epidermal growth factor.
      In malignant ascites, LPA is present at a high level, which can explain the
      migration activity, and the fractionation study of ascites by lipid extraction
      and subsequent thin-layer chromatography indicated LPA as an active component. A
      significant level of LPA1 receptor mRNA is expressed in pancreatic cancer cells
      with high migration activity to ascites but not in cells with low migration
      activity. Small interfering RNA against LPA1 receptors specifically inhibited the
      receptor mRNA expression and abolished the migration response to ascites. These
      results suggest that LPA is a critical component of ascites for the motility of
      pancreatic cancer cells and LPA1 receptors may mediate this activity. LPA
      receptor antagonists including Ki16425 are potential therapeutic drugs against
      the migration and invasion of cancer cells.

PMID- 14660631
TI  - The role of phosphorylation in D1 dopamine receptor desensitization: evidence for
      a novel mechanism of arrestin association.
AB  - Homologous desensitization of D(1) dopamine receptors is thought to occur through
      their phosphorylation leading to arrestin association which interdicts G protein
      coupling. In order to identify the relevant domains of receptor phosphorylation,
      and to determine how this leads to arrestin association, we created a series of
      mutated D(1) receptor constructs. In one mutant, all of the serine/threonine
      residues within the 3rd cytoplasmic domain were altered (3rdTOT). A second
      construct was created in which only three of these serines (serines 256, 258, and
      259) were mutated (3rd234). We also created four truncation mutants of the
      carboxyl terminus (T347, T369, T394, and T404). All of these constructs were
      comparable with the wild-type receptor with respect to expression and adenylyl
      cyclase activation. In contrast, both of the 3rd loop mutants exhibited
      attenuated agonist-induced receptor phosphorylation that was correlated with an
      impaired desensitization response. Sequential truncation of the carboxyl terminus
      of the receptor resulted in a sequential loss of agonist-induced phosphorylation.
      No phosphorylation was observed with the most severely truncated T347 mutant.
      Surprisingly, all of the truncated receptors exhibited normal desensitization.
      The ability of the receptor constructs to promote arrestin association was
      evaluated using arrestin-green fluorescent protein translocation assays and
      confocal fluorescence microscopy. The 3rd234 mutant receptor was impaired in its
      ability to induce arrrestin translocation, whereas the T347 mutant was comparable
      with wild type. Our data suggest a model in which arrestin directly associates
      with the activated 3rd cytoplasmic domain in an agonist-dependent fashion;
      however, under basal conditions, this is sterically prevented by the carboxyl
      terminus of the receptor. Receptor activation promotes the sequential
      phosphorylation of residues, first within the carboxyl terminus and then the 3rd
      cytoplasmic loop, thereby dissociating these domains and allowing arrestin to
      bind to the activated 3rd loop. Thus, the role of receptor phosphorylation is to
      allow access of arrestin to its receptor binding domain rather than to create an
      arrestin binding site per se.

PMID- 14660632
TI  - 1H NMR investigation of the solution structure of substrate-free human heme
      oxygenase: comparison to the cyanide-inhibited, substrate-bound complex.
AB  - 1H NMR was used to investigate the molecular structure, and dynamic properties of
      soluble, recombinant, substrate-free human heme oxygenase (apohHO) on a
      comparative basis with similar studies on the substrate complex. Limited but
      crucial sequence-specific assignments identify five conserved secondary
      structural elements, and the detection of highly characteristic dipolar or H-bond
      interactions among these elements together with insignificant chemical shift
      differences confirm a strongly conserved folding topology of helices C-H relative
      to that of substrate complexes in either solution or the crystal. The correction
      of the chemical shifts for paramagnetic and porphyrin ring current influences in
      the paramagnetic substrate complex reveals that the strength of all but one of
      the numerous relatively robust H-bonds are conserved in apohHO, and similar
      ordered water molecules are located near these H-bond donors as observed in the
      substrate complexes. The unique and significant weakening of the Tyr(58) OH
      hydrogen bond to the catalytically critical Asp(140) carboxylate in apohHO is
      suggested to arise from the removal of the axial H-bond acceptor ligand rather
      than the loss of substrate. The interhelical positions of the conserved strong H
      bonds argue for a structural role in maintaining a conserved structure for
      helices C-H upon loss of substrate. While the structure and H-bond network are
      largely conserved upon loss of substrate, the variably increased rate of NH
      lability dictates a significant loss of dynamic stability in the conserved
      structure, particularly near the distal helix F.

PMID- 14660633
TI  - Homology modeling of the transmembrane domain of the human calcium sensing
      receptor and localization of an allosteric binding site.
AB  - A homology model for the human calcium sensing receptor (hCaR) transmembrane
      domain utilizing bovine rhodopsin (bRho) structural information was derived and
      tested by docking the allosteric antagonist, NPS 2143, followed by mutagenesis of
      predicted contact sites. Mutation of residues Phe-668 (helix II), Arg-680, or Phe
      684 (helix III) to Ala (or Val or Leu) and Glu-837 (helix VII) to Ile (or Gln)
      reduced the inhibitory effects of NPS 2143 on [Ca2+]i responses. The calcimimetic
      NPS R-568 increases the potency of Ca2+ in functional assays of CaR. Mutations at
      Phe-668, Phe-684, or Glu-837 attenuated the effects of this compound, but
      mutations at Arg-680 had no effect. In all cases, mutant CaRs responded normally
      to Ca2+ or phenylalanine, which act at distinct site(s). Discrimination by the
      Arg-680 mutant is consistent with the structural differences between NPS 2143,
      which contains an alkyl bridge hydroxyl group, and NPS R-568, which does not. The
      homology model of the CaR transmembrane domain robustly accounts for binding of
      both an allosteric antagonist and agonist, which share a common site, and
      provides a basis for the development of more specific and/or potent allosteric
      modulators of CaR. These studies suggest that the bRho backbone can be used as a
      starting point for homology modeling of even distantly related G protein-coupled
      receptors and provide a rational framework for investigation of the contributions
      of the transmembrane domain to CaR function.

PMID- 14660634
TI  - Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates
      transcription.
AB  - Post-translational modifications of the histone protein components of eukaryotic
      chromatin play an important role in the regulation of chromatin structure and
      gene expression (1). Given the requirement of Rad6/Bre1-dependent ubiquitination
      of histone H2B for H3 dimethylation (at lysines 4 and 79) and gene silencing (2
      7), removal of ubiquitin from H2B may have a significant regulatory effect on
      transcription. Here we show that a putative deubiquitinating enzyme, Ubp8, is a
      structurally nonessential component of both the Spt-Ada-Gcn5-acetyltransferase
      (SAGA) and SAGA-like (SLIK) histone acetyltransferase (HAT) complexes in yeast.
      Disruption of this gene dramatically increases the cellular level of
      ubiquitinated-H2B, and SAGA and SLIK are shown to have H2B deubiquitinase
      activity. These findings demonstrate, for the first time, how the ubiquitin
      moiety can be removed from histone H2B in a regulated fashion. Ubp8 is required
      for full expression of the SAGA- and SLIK-dependent gene GAL10 and is recruited
      to the upstream activation sequence (UAS) of this gene under activating
      conditions, while Rad6 dissociates. Furthermore, trimethylation of H3 at lysine 4
      within the UAS increases significantly under activating conditions, and
      remarkably, Ubp8 is shown to have a role in regulating the methylation status of
      this residue. Collectively, these data suggest that the SAGA and SLIK HAT
      complexes can regulate an integrated set of multiple histone modifications,
      counteracting repressive effects that alter chromatin and regulate gene
      expression.

PMID- 14660635
TI  - Carbohydrates induce mono-ubiquitination of H2B in yeast.
AB  - Histone modifications have emerged to be a major regulatory mechanism for gene
      expression (1-4). However, it is not clear how histone modifications are
      physiologically regulated. Here, we show that mono-ubiquitinated H2B at lysine
      123 (uH2B) in the yeast (Saccharomyces cerevisiae) is present in exponential
      phase and absent in stationary phase. A wide array of carbohydrates or sugars,
      including glucose, fructose, mannose, and sucrose, are capable of inducing uH2B
      in stationary phase yeast. In contrast, non-metabolic glucose analogs are
      defective in inducing uH2B. Furthermore, uH2B induction is inhibited by
      iodoacetate, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase in
      glycolysis. Moreover, uH2B induction is markedly impaired in yeast mutants, in
      which glycolytic genes are deleted. These data indicate that glycolysis is
      required for the carbohydrate-induced mono-ubiquitination of H2B at lysine 123.
      Therefore, our study reveals a novel paradigm of metabolic regulation of histone
      modifications.

PMID- 14660636
TI  - Heme positively regulates the expression of beta-globin at the locus control
      region via the transcriptional factor Bach1 in erythroid cells.
AB  - The transcription factor Bach1 heterodimerizes with small Maf proteins to repress
      Maf recognition element (MARE)-dependent gene expression. The repressor activity
      of Bach1 is inhibited by the direct binding of heme. To investigate the
      involvement of Bach1 in the heme-dependent regulation of the expression of the
      beta-globin gene, mouse erythroleukemia (MEL) cells were cultured with
      succinylacetone (SA), a specific inhibitor of heme biosynthesis, and the level of
      beta-globin mRNA was examined. A marked decrease of beta-globin mRNA in SA
      treated cells was observed, and this decrease was reversed by the addition of
      hemin. An iron chelator, desferrioxamine, also lowered the level of beta-globin
      mRNA. The heme-dependent expression of beta-globin is a transcriptional event
      since the expression of the human beta-globin gene promoter-reporter gene
      containing the microlocus control region (microLCR) was inhibited when human
      erythroleukemia K562 cells and MEL cells were cultured with SA. Hemin treatment
      restored the decrease in promoter activity caused by SA. The control of the
      microLCR-beta-globin promoter reporter gene by heme was dependent on DNase I
      hypersensitive site 2 (HS2), which contains MARE. The MARE binding activity of
      Bach1 in K562 and MEL cells increased upon SA treatment, and the increase was
      diminished by the treatment with hemin. Transient expression of Bach1 suppressed
      the microLCR activity, and this repressor activity was cancelled by treatment
      with hemin. The expression of a mutated Bach1 lacking heme-binding sites led to a
      loss in the heme responsiveness of the microLCR. Furthermore, chromatin
      immunoprecipitation experiments revealed that Bach1 bound to the MARE of HS2
      increased by the treatment of MEL cells with SA, and this was cancelled by hemin.
      We propose that heme positively regulates the beta-globin gene expression by
      blocking the interaction of Bach1 with the MARE in the LCR.

PMID- 14660637
TI  - Direct interaction of major histocompatibility complex class II-derived peptides
      with class Ia phosphoinositide 3-kinase results in dose-dependent stimulatory
      effects.
AB  - Peptides corresponding to residues 65-79 of human lymphocyte antigen class II
      sequence (DQA*03011) are cell-permeable and at high concentrations block
      activation of protein kinase B/Akt and p70-S6 kinase in T-cells, effects
      attributed to inhibition of phosphoinositide (PI) 3-kinase activity. To
      understand the molecular basis of this, we analyzed the effect this peptide had
      on activity of class I PI 3-kinases. Although there was no effect on the activity
      of class Ib PI 3-kinase or on the protein kinase activity of class I PI 3
      kinases, there was a biphasic effect on lipid kinase activity of the class Ia
      enzymes. There was an inhibition of activity at higher peptide concentrations
      because of a formation of insoluble complexes between peptide and enzyme.
      Conversely, at lower peptide concentrations there was a profound activation of PI
      3-kinase activity of class Ia PI 3-kinases. Studies of peptide variants revealed
      that all active peptides conform to heptad repeat motifs characteristic of coiled
      coil helices. Surface plasmon resonance studies confirmed direct sequence
      specific binding of active peptide to the p85alpha adapter subunit of class Ia PI
      3-kinase. Active peptides also activated protein kinase B and extracellular
      signal-regulated kinase (ERK) in vivo in a wortmannin-sensitive manner while
      reducing recoverable cellular p85 levels. These results indicate that the human
      lymphocyte antigen class II-derived peptides regulate PI 3-kinase by direct
      interaction, probably via the coiled-coil domain. These peptides define a novel
      mechanism of regulating PI 3-kinase and will provide a useful tool for
      specifically dissecting the function of class Ia PI 3-kinase in cells and for
      probing structure-function relationships in the class Ia PI 3-kinase
      heterodimers.

PMID- 14660638
TI  - Improved catalytic efficiency and active site modification of 1,4-beta-D-glucan
      glucohydrolase A from Thermotoga neapolitana by directed evolution.
AB  - Thermotoga neapolitana 1,4-beta-d-glucan glucohydrolase A preferentially
      hydrolyzes cello-oligomers, such as cellotetraose, releasing single glucose
      moieties from the reducing end of the cello-oligosaccharide chain. Using directed
      evolution techniques of error-prone PCR and mutant library screening, a variant
      glucan glucohydrolase has been isolated that hydrolyzes the disaccharide,
      cellobiose, at a 31% greater rate than its wild type (WT) predecessor. The mutant
      library, expressed in Escherichia coli, was screened at 85 degrees C for
      increased hydrolysis of cellobiose, a native substrate rather than a chromogenic
      analog, using a continuous, thermostable coupled enzyme assay. The V(max) for the
      mutant was 108 +/- 3 units mg(-1), whereas that of the WT was 75 +/- 2 units mg(
      1). The K(m) for both proteins was nearly the same. The k(cat) for the new enzyme
      increased by 31% and its catalytic efficiency (k(cat)/K(m)) for cellobiose also
      rose by 31% as compared with the parent. The nucleotide sequence of two positive
      clones and two null clones identified 11 single base shifts. The nucleotide
      transition in the most active clone caused an isoleucine to threonine amino acid
      substitution at position 170. Structural models for I170T and WT proteins were
      derived by sequence homology with Protein Data Bank code 1BGA from Paenibacillus
      polymyxa. Analysis of the WT and I170T model structures indicated that the
      substitution in the mutant enzyme repositioned the conserved catalytic residue
      Asn-163 and reconfigured entry to the active site.

PMID- 14660639
TI  - Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide
      (SLC10A1) reveals a domain critical for bile acid substrate recognition.
AB  - The key transporter responsible for hepatic uptake of bile acids from portal
      circulation is Na+-taurocholate cotransporting polypeptide (NTCP, SLC10A1). This
      transporter is thought to be critical for the maintenance of enterohepatic
      recirculation of bile acids and hepatocyte function. Therefore, functionally
      relevant polymorphisms in this transporter would be predicted to have an
      important impact on bile acid homeostasis/liver function. However, little is
      known regarding genetic heterogeneity in NTCP. In this study, we demonstrate the
      presence of multiple single nucleotide polymorphisms in NTCP in populations of
      European, African, Chinese, and Hispanic Americans. Specifically four
      nonsynonymous single nucleotide polymorphisms associated with a significant loss
      of transport function were identified. Cell surface biotinylation experiments
      indicated that the altered transport activity of T668C (Ile223-->Thr), a variant
      seen only in African Americans, was due at least in part to decreased plasma
      membrane expression. Similar expression patterns were observed when the variant
      alleles were expressed in HepG2 cells, and plasma membrane expression was
      assessed using immunofluorescence confocal microscopy. Interestingly the C800T
      (Ser267-->Phe) variant, seen only in Chinese Americans, exhibited a near complete
      loss of function for bile acid uptake yet fully normal transport function for the
      non-bile acid substrate estrone sulfate, suggesting this position may be part of
      a region in the transporter critical and specific for bile acid substrate
      recognition. Accordingly, our study indicates functionally important
      polymorphisms in NTCP exist and that the likelihood of being carriers of such
      polymorphisms is dependent on ethnicity.

PMID- 14660640
TI  - Thyroid-stimulating hormone/cAMP and glycogen synthase kinase 3beta elicit
      opposing effects on Rap1GAP stability.
AB  - Beyond regulating Rap activity, little is known regarding the regulation and
      function of the Rap GTPase-activating protein Rap1GAP. Tuberin and E6TP1 protein
      levels are tightly regulated through ubiquitin-mediated proteolysis. A role for
      these RapGAPs, along with SPA-1, as tumor suppressors has been demonstrated.
      Whether Rap1GAP performs a similar role was investigated. We now report that
      Rap1GAP protein levels are dynamically regulated in thyroid-stimulating hormone
      (TSH)-dependent thyroid cells. Upon TSH withdrawal, Rap1GAP undergoes a net
      increase in phosphorylation followed by proteasome-mediated degradation. Sequence
      analysis identified two putative destruction boxes in the Rap1GAP C-terminal
      domain. Glycogen synthase kinase 3beta (GSK3beta) phosphorylated Rap1GAP
      immunoprecipitated from thyroid cells, and GSK3beta inhibitors prevented
      phosphorylation and degradation of endogenous Rap1GAP. Co-expression of GSK3beta
      and Rap1GAP in human embryonic kidney 293 cells stimulated proteasome-dependent
      Rap1GAP turnover. Mutational analysis established a role for serine 525 in the
      regulation of Rap1GAP stability. Overexpression of Rap1GAP in thyroid cells
      impaired TSH/cAMP-stimulated p70S6 kinase activity and cell proliferation. These
      data are the first to show that Rap1GAP protein levels are tightly regulated and
      are the first to support a role for Rap1GAP as a tumor suppressor.

PMID- 14660642
TI  - Identification of an additional interaction domain in transmembrane domains 11
      and 12 that supports oligomer formation in the human serotonin transporter.
AB  - Na+/Cl--dependent neurotransmitter transporters form constitutive oligomers. The
      topological arrangement is not known, but a leucine heptad repeat in
      transmembrane domain (TM) 2 and a glycophorin-like motif in TM6 have been
      proposed to stabilize the oligomer. To determine the topology, we generated
      versions of the human serotonin transporter (hSERT) that carried cyan or yellow
      fluorescent proteins at their amino and/or carboxyl terminus. Appropriate pairs
      were coexpressed to measure fluorescence resonance energy transfer (FRET). Donor
      photobleaching FRET microscopy was employed to deduce the following arrangement:
      within the monomer, the amino and carboxyl termini are in close vicinity. In
      addition, in the oligomer, the carboxyl termini are closer to each other than the
      amino termini. Hence, a separate interaction domain (i.e. distinct from TM2 and
      TM6) must reside in the carboxyl-terminal half of hSERT. This was confirmed by
      expressing the amino- and carboxyl-terminal halves of hSERT. These were retained
      intracellularly; they also retained the coexpressed full-length transporter by
      forming export-deficient oligomers and, when cotransfected in all possible
      combinations, supported FRET. Hence, both the carboxyl and amino termini contain
      elements that drive oligomerization. By employing fragments comprising two
      neighboring TM helices, we unequivocally identified TM11/12 as a new contact site
      by donor photobleaching FRET and beta-lactamase protein fragment complementation
      assay. TM1/2 was also found to self-associate. Thus, oligomerization of hSERT
      involves at least two discontinuous interfaces. The currently identified
      interaction sites drive homophilic interactions. This is consistent with assembly
      of SERT oligomers in an array-like structure containing multimers of dimers.

PMID- 14660641
TI  - A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D.
AB  - RRAG A (Rag A)/Gtr1p is a member of the Ras-like small G protein family that
      genetically interacts with RCC1, a guanine nucleotide exchange factor for
      RanGTPase. RRAG A/Gtr1p forms a heterodimer with other G proteins, RRAG C and
      RRAG D/Gtr2p, in a nucleotide-independent manner. To further elucidate the
      function of RRAG A/Gtr1p, we isolated a protein that interacts with RRAG A. This
      protein is a novel nucleolar protein, Nop132. Nop132 is associated with the GTP
      form, but not the GDP form, of RRAG A, suggesting that RRAG A might regulate
      Nop132 function. Nop132 is also associated with RRAG C and RRAG D. The Nop132
      amino acid sequence is similar to the Saccharomyces cerevisiae nucleolar Nop8p,
      which is associated with Gtr1p, Gtr2p, and Nip7p. Nop132 also interacts with
      human Nip7 and is colocalized with RRAG A, RRAG C, and Nip7. RNA interference
      knockdown of Nop132 inhibited cell growth of HeLa cells.

PMID- 14660643
TI  - Increased calcium influx and ribosomal content correlate with resistance to
      endoplasmic reticulum stress-induced cell death in mutant leukemia cell lines.
AB  - Cell clones were derived by treatment of HL-60 cells with stepwise increasing
      concentrations of econazole (Ec), an imidazole antifungal that blocks Ca2+ influx
      and induces endoplasmic reticulum (ER) stress-related cell death in multiple
      mammalian cell types. Clones exhibit 20- to more than 300-fold greater resistance
      to Ec. Unexpectedly, they also display stable cross-resistance to tunicamycin,
      thapsigargin, dithiothreitol, and cycloheximide but not doxorubicin, etoposide,
      or Fas ligand. Phenotypic analysis indicates that the cells display increased
      store-operated calcium influx and resistance to ER Ca2+ store depletion by Ec.
      E2R2, the most resistant clone, was observed to maintain protein synthesis levels
      after treatment with Ec or thapsigargin. Expression of GRP78, an ER-based
      chaperone, was induced by these ER stress treatments but to equal degrees in HL
      60 and E2R2 cells. By using microarray analysis, at least 15 ribosomal protein
      genes were found to be overexpressed in E2R2 compared with HL-60 cells. We also
      found that ribosomal protein content was increased by 30% in E2R2 as well as
      other clones. The resistance phenotype was partially reversed by the ribosome
      inactivating protein saporin. Therefore, increased store-operated calcium influx,
      resistance to ER Ca2+ store depletion, and overexpression of ribosomal proteins
      define a novel phenotype of ER stress-associated multidrug resistance.

PMID- 14660644
TI  - Aspartate 345 of the dopamine transporter is critical for conformational changes
      in substrate translocation and cocaine binding.
AB  - The present study elucidated the role of aspartate 345, a residue conserved in
      the third intracellular loop of all Na+/Cl(-)-dependent neurotransmitter
      transporters, in conformational changes of the dopamine (DA) transporter.
      Asparagine substitution (D345N) resulted in near normal transporter expression on
      the cell surface but caused extremely low Vmax and Km values for DA uptake,
      converted the inhibitory effect of Zn2+ on DA uptake to a stimulatory one, and
      eliminated reverse transport. The cocaine-like inhibitor 2beta-carbomethoxy-3beta
      (4-fluorophenyl)tropane or the selective DA transporter inhibitor GBR12935 bound
      to D345N with a normal affinity and still inhibited DA uptake potently. However,
      the mutation reduced the binding capacity of the surface transporter for these
      two inhibitors by 90% or more. Moreover, the binding activity of D345N can be
      significantly improved by Zn2+ but not by Na+. These results are consistent with
      a defect in reorientation of the substrate-binding site to the extracellular
      side, leading to a loss of the outward-facing conformational state where external
      DA binds to initiate uptake and the inhibitors bind to initiate uptake
      inhibition. Alanine or glutamate substitution produced a similar phenotype,
      suggesting that both the negative charge and the residue volume at position 345
      are vital. Furthermore, in intact cells, cocaine potentiated the reaction of the
      membrane-impermeant sulfhydryl reagent methanethiosulfonate
      ethyltrimethylammonium with the extracellularly located endogenous cysteines of
      D345N but not those of wild type, and this potentiation was blocked upon K+
      substitution for Na+. Thus, cocaine binding to D345N likely induces a different
      and Na(+)-dependent conformational change, which may contribute to its Na(+)
      dependent uptake inhibitory activity.

PMID- 14660645
TI  - Involvement of toll-like receptors 2 and 4 in cellular activation by high
      mobility group box 1 protein.
AB  - High mobility group box 1 (HMGB1) protein, originally described as a DNA-binding
      protein that stabilizes nucleosomes and facilitates transcription, can also be
      released extracellularly during acute inflammatory responses. Exposure of
      neutrophils, monocytes, or macrophages to HMGB1 results in increased nuclear
      translocation of NF-kappaB and enhanced expression of proinflammatory cytokines.
      Although the receptor for advanced glycation end products (RAGE) has been shown
      to interact with HMGB1, other putative HMGB1 receptors are known to exist but
      have not been characterized. In the present experiments, we explored the role of
      RAGE, Toll-like receptor (TLR) 2, and TLR 4, as well as associated kinases, in
      HMGB1-induced cellular activation. Culture of neutrophils or macrophages with
      HMGB1 produced activation of NF-kappaB through TLR 4-independent mechanisms.
      Unlike lipopolysaccharide (LPS), which primarily increased the activity of
      IKKbeta, HMGB1 exposure resulted in activation of both IKKalpha and IKKbeta.
      Kinases and scaffolding proteins downstream of TLR 2 and TLR 4, but not
      TLR/interleukin-1 receptor (IL-1R)-independent kinases such as tumor necrosis
      factor receptor-associated factor 2, were involved in the enhancement of NF
      kappaB-dependent transcription by HMGB1. Transfections with dominant negative
      constructs demonstrated that TLR 2 and TLR 4 were both involved in HMGB1-induced
      activation of NF-kappaB. In contrast, RAGE played only a minor role in macrophage
      activation by HMGB1. Interactions of HMGB1 with TLR 2 and TLR 4 may provide an
      explanation for the ability of HMGB1 to generate inflammatory responses that are
      similar to those initiated by LPS.

PMID- 14660646
TI  - Recovery from DNA damage-induced G2 arrest requires actin-binding protein filamin
      A/actin-binding protein 280.
AB  - Filamin-A (filamin-1) is an actin-binding protein involved in the organization of
      actin networks. Our previous study shows that filamin-A interacts with BRCA2, and
      lack of filamin-A expression results in increased cellular sensitivity to several
      DNA damaging agents in melanoma cells (Yuan, Y., and Shen, Z. (2001) J. Biol.
      Chem. 276, 48318-48324), suggesting a role of filamin-A in DNA damage response.
      In this report, we demonstrated that deficiency of filamin-A results in an 8-h
      delay in the recovery from G2 arrest in response to ionizing radiation. However,
      filamin-A deficiency does not affect the initial activation of the G2/M
      checkpoint. We also found that filamin-A deficiency results in sustained
      activation of Chk1 and Chk2 after irradiation. This in turn causes a delay in the
      dephosphorylation of phospho-Cdc2, which is inhibitory to the G2/M transition. In
      addition, filamin-A-deficient M2 cells undergo mitotic catastrophe-related
      nuclear fragmentation after they are released from the G2 arrest. Together, these
      data suggest a functional role of filamin-A in the recovery from G2 arrest and
      subsequent mitotic cell death after DNA damage.

PMID- 14660647
TI  - The paired activation of the two components of the muscarinic M3 receptor dimer
      is required for induction of ERK1/2 phosphorylation.
AB  - Muscarinic M(3) receptors stimulate ERK1/2, the mitogen-activated protein kinase
      pathway. A mutant of the muscarinic M(3) receptor in which most of the third
      intracellular (i3) loop had been deleted (M(3)-short) completely lost the ability
      to stimulate the ERK1/2 phosphorylation in COS-7 cells. This loss was evident
      despite the fact that the receptor was able to couple efficiently to the
      phospholipase C second messenger pathway. In co-transfected cells, M(3)-short
      greatly reduced the ability of M(3) to activate ERK1/2. In another set of
      experiments we tested the ability of a mutant M(3)/M(2)(16aa) receptor, in which
      the first 16 amino acids of the i3 loop of the M(3) receptor were replaced with
      the corresponding segment of the muscarinic M(2) receptor to stimulate ERK1/2
      phosphorylation. This mutant is not coupled to Galpha(q), but it is weakly
      coupled to Galpha(i). Despite its coupling modification this receptor was able to
      stimulate ERK1/2 phosphorylation. Again, M(3)-short greatly reduced the ability
      of M(3)/M(2)(16aa) to activate ERK1/2 in co-transfected cells. Similar results
      were obtained in stable-transfected Chinese hamster ovary (CHO) cells lines. In
      CHO M(3) cells carbachol induced a biphasic increase of ERK1/2 phosphorylation; a
      first increase at doses as low as 0.1 microm and a second increase starting from
      10 microm. In CHO M(3)-short and in double-transfected CHO M(3)/M(3)-short cells
      we observed only the lower doses increase of ERK1/2 phosphorylation; no further
      increase was observed up to 1 mm carbachol. This suggests that in double
      transfected CHO cells M(3)-short prevents the effect of the higher doses of
      carbachol on the M(3) receptor. In a final experiment we tested the ability of co
      transfected chimeric alpha(2)/M(3) and M(3)/alpha(2) receptors to activate the
      ERK1/2 pathway. When given alone, carbachol and, to a lesser extent, clonidine,
      stimulated the coupling of the co-transfected chimeric receptors to the
      phospholipase C second messenger pathway, but they were unable to stimulate
      ERK1/2 phosphorylation. On the contrary, a strong stimulation of ERK1/2
      phosphorylation was observed when the two agonists were given together despite
      the fact that the overall increase in phosphatidylinositol hydrolysis was not
      dissimilar from that observed in cells treated with carbachol alone. Our data
      suggest that the activation of the ERK1/2 pathway requires the coincident
      activation of the two components of a receptor dimer.

PMID- 14660648
TI  - Molecular and cellular physiology of apolipoprotein A-I lipidation by the ATP
      binding cassette transporter A1 (ABCA1).
AB  - The dynamics of ABCA1-mediated apoA-I lipidation were investigated in intact
      human fibroblasts induced with 22(R)-hydroxycholesterol and 9-cis-retinoic acid
      (stimulated cells). Specific binding parameters of (125)I-apoA-I to ABCA1 at 37
      degrees C were determined: K(d) = 0.65 microg/ml, B(max) = 0.10 ng/microg cell
      protein. Lipid-free apoA-I inhibited the binding of (125)I-apoA-I to ABCA1 more
      efficiently than pre-beta(1)-LpA-I, reconstituted HDL particles r(LpA-I), or
      HDL(3) (IC(50) = 0.35 +/- 1.14, apoA-I; 1.69 +/- 1.07, pre-beta(1)-LpA-I; 17.91
      +/- 1.39, r(LpA-I); and 48.15 +/- 1.72 microg/ml, HDL(3)). Treatment of intact
      cells with either phosphatidylcholine-specific phospholipase C or
      sphingomyelinase affected neither (125)I-apoA-I binding nor (125)I-apoA-I/ABCA1
      cross-linking. We next investigated the dynamics of apoA-I lipidation by
      monitoring the kinetic of apoA-I dissociation from ABCA1. The dissociation of
      (125)I-apoA-I from normal cells at 37 degrees C was rapid (t((1/2)) = 1.4 +/-
      0.66 h; n = 3) but almost completely inhibited at either 15 or 4 degrees C. A
      time course analysis of apoA-I-containing particles released during the
      dissociation period showed nascent apoA-I-phospholipid complexes that exhibited
      alpha-electrophoretic mobility with a particle size ranging from 9 to 20 nm
      (designated alpha-LpA-I-like particles), whereas lipid-free apoA-I incubated with
      ABCA1 mutant (Q597R) cells was unable to form such particles. These results
      demonstrate that: 1) the physical interaction of apoA-I with ABCA1 does not
      depend on membrane phosphatidylcholine or sphingomyelin; 2) the association of
      apoA-I with lipids reduces its ability to interact with ABCA1; and 3) the lipid
      translocase activity of ABCA1 generates alpha-LpA-I-like particles. This process
      plays in vivo a key role in HDL biogenesis.

PMID- 14660649
TI  - Reversible transport by the ATP-binding cassette multidrug export pump LmrA: ATP
      synthesis at the expense of downhill ethidium uptake.
AB  - The ATP dependence of ATP-binding cassette (ABC) transporters has led to the
      widespread acceptance that these systems are unidirectional. Interestingly, in
      the presence of an inwardly directed ethidium concentration gradient in ATP
      depleted cells of Lactococcus lactis, the ABC multidrug transporter LmrA mediated
      the reverse transport (or uptake) of ethidium with an apparent K(t) of 2.0
      microm. This uptake reaction was competitively inhibited by the LmrA substrate
      vinblastine and was significantly reduced by an E314A substitution in the
      membrane domain of the transporter. Similar to efflux, LmrA-mediated ethidium
      uptake was inhibited by the E512Q replacement in the Walker B region of the
      nucleotide-binding domain of the protein, which strongly reduced its drug
      stimulated ATPase activity, consistent with published observations for other ABC
      transporters. The notion that ethidium uptake is coupled to the catalytic cycle
      in LmrA was further corroborated by studies in LmrA-containing cells and
      proteoliposomes in which reverse transport of ethidium was associated with the
      net synthesis of ATP. Taken together, these data demonstrate that the
      conformational changes required for drug transport by LmrA are (i) not too far
      from equilibrium under ATP-depleted conditions to be reversed by appropriate
      changes in ligand concentrations and (ii) not necessarily coupled to ATP
      hydrolysis, but associated with a reversible catalytic cycle. These findings and
      their thermodynamic implications shed new light on the mechanism of energy
      coupling in ABC transporters and have implications for the development of new
      modulators that could enable reverse transport-associated drug delivery in cells
      through their ability to uncouple ATP binding/hydrolysis from multidrug efflux.

PMID- 14660650
TI  - Sequence and spacing of TATA box elements are critical for accurate initiation
      from the beta-phaseolin promoter.
AB  - The beta-phaseolin (phas) gene, which encodes one of the major seed storage
      proteins of P. vulgaris, is tightly regulated at the transcription level
      resulting in strict tissue-specific and spatial expression during embryonic
      development. The phas proximal promoter contains a complex arrangement of core
      promoter elements including three TATA boxes as well as several putative
      initiator elements. To delineate the respective contributions of the core
      promoter elements to transcription initiation we have performed site-directed
      mutagenesis of the phas promoter. In vivo expression studies were performed on
      transgenic Arabidopsis harboring phas promoter mutants driving expression of the
      beta-glucuronidase (gus) reporter gene. Quantitative assessment of GUS activity
      in seeds bearing the promoter mutants indicated that both sequence and spacing of
      the TATA elements influenced the efficiency of transcription. Substitution,
      insertion or deletion mutations had no effect on histochemical staining patterns
      indicating that strict spacing requirements are not essential for correct spatial
      expression of phas during embryogenesis. Further evaluation of the phas promoter
      by in vitro transcription analysis revealed the presence of multiple TATA
      dependent transcription initiation start sites. The distance between TATA
      elements and transcription start sites was maintained in insertion and deletion
      mutants through the creation of novel initiation sites, indicating that
      positioning of the TATA elements rather than DNA sequence was the primary
      determinant of start site location. We conclude that, while dispensable for
      proper spatial distribution, the complex architecture of the phas promoter is
      required to ensure high levels of accurate phas transcription initiation in the
      developing embryo.

PMID- 14660651
TI  - Negative regulation of HER2 signaling by the PEST-type protein-tyrosine
      phosphatase BDP1.
AB  - Signaling by receptor tyrosine kinases (RTK) mediates a variety of complex
      cellular functions and in case of deregulation can contribute to
      pathophysiological processes. A tight and finely tuned control of RTK activity is
      therefore critical for the cell. We investigated the role of the PEST-type
      protein-tyrosine phosphatase BDP1 in the regulation of HER2, a member of the
      epidermal growth factor receptor (EGFR) family of RTKs. Here we demonstrate that
      HER2 signaling is highly sensitive to BDP1 activity. Overexpression of BDP1
      inhibited ligand-induced activation of HER2 but not that of the closely related
      EGFR. On the other hand, suppression of endogenous BDP1 expression increased the
      phosphorylation state of HER2. In addition, BDP1 was able to interfere with
      downstream signaling events by inhibiting the phosphorylation of the adaptor
      protein Gab1 and reducing mitogen-activated protein kinase activation. Supported
      by the finding that BDP1 is coexpressed with HER2 in breast cancer cells, we
      suggest that BDP1 is an important regulator of HER2 activity and thus the first
      protein-tyrosine phosphatase shown to be involved in HER2 signal attenuation.

PMID- 14660652
TI  - Biochemical and molecular characterization of ACH2, an acyl-CoA thioesterase from
      Arabidopsis thaliana.
AB  - By using computer-based homology searches of the Arabidopsis genome, we
      identified the gene for ACH2, a putative acyl-CoA thioesterase. With the
      exception of a unique 129-amino acid N-terminal extension, the ACH2 protein is 17
      36% identical to members of a family of acyl-CoA thioesterases that are found in
      both prokaryotes and eukaryotes. The eukaryotic homologs of ACH2 are peroxisomal
      acyl-CoA thioesterases that are up-regulated during times of increased fatty acid
      oxidation, suggesting potential roles in peroxisomal beta-oxidation. We
      investigated ACH2 to determine whether it has a similar role in the plant cell.
      Like its eukaryotic homologs, ACH2 carries a putative type 1 peroxisomal
      targeting sequence (-SKL(COOH)), and maintains all the catalytic residues typical
      of this family of acyl-CoA thioesterases. Analytical ultracentrifugation of
      recombinant ACH2-6His shows that it associates as a 196-kDa homotetramer in
      vitro, a result that is significant in light of the cooperative kinetics
      demonstrated by ACH2-6His in vitro. The cooperative effects are most pronounced
      with medium chain acyl-CoAs, where the Hill coefficient is 3.8 for lauroyl-CoA,
      but decrease for long chain acyl-CoAs, where the Hill coefficient is only 1.9 for
      oleoyl-CoA. ACH2-6His hydrolyzes both medium and long chain fatty acyl-CoAs but
      has highest activity toward the long chain unsaturated fatty acyl-CoAs. Maximum
      rates were found with palmitoleoyl-CoA, which is hydrolyzed at 21 micromol/min/mg
      protein. Additionally, ACH2-6His is insensitive to feedback inhibition by free
      CoASH levels as high as 100 microm. ACH2 is most highly expressed in mature
      tissues such as young leaves and flowers rather than in germinating seedlings
      where beta-oxidation is rapidly proceeding. Taken together, these results suggest
      that ACH2 activity is not linked to fatty acid oxidation as has been suggested
      for its eukaryotic homologs, but rather has a unique role in the plant cell.

PMID- 14660653
TI  - A Rho exchange factor mediates fMet-Leu-Phe-induced NF-kappaB activation in human
      peripheral blood monocytes.
AB  - We reported previously that fMLP stimulates NF-kappaB activation, and this
      function of fMLP requires small GTPase RhoA in human peripheral blood monocytes
      (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol.
      Chem. 276, 40977-40981). Here we present evidence that RhoA associates
      specifically with the guanine nucleotide exchange factor Lbc in human peripheral
      blood monocytes stimulated with fMLP and that Lbc specifically catalyzes the
      guanine nucleotide exchange activity of RhoA in human peripheral blood monocytes.
      Cotransfection of the monocytic THP1 cells with lbc with a kappaB promoter
      reporter plasmid results in a marked increase in NF-kappaB-mediated reporter gene
      expression. Finally, Lbc-enhanced NF-kappaB activation is inhibited by a RhoA
      inhibitor, C3 transferase from Clostridium botulinum. A dominant-negative form of
      RhoA (T19N) also inhibited Lbc-enhanced reporter gene expression in a kappaB
      dependent manner. These results indicate that guanine nucleotide exchange factor
      Lbc is a novel signal transducer for RhoA-mediated NF-kappaB activation in human
      peripheral blood monocytes stimulated with bacterial products.

PMID- 14660654
TI  - The apolipoprotein(a) component of lipoprotein(a) stimulates actin stress fiber
      formation and loss of cell-cell contact in cultured endothelial cells.
AB  - Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a risk factor for a
      variety of atherosclerotic disorders including coronary heart disease. In the
      current study, we report that incubation of cultured human umbilical vein or
      coronary artery endothelial cells with Lp(a) elicits a dramatic rearrangement of
      the actin cytoskeleton characterized by increased central stress fiber formation
      and redistribution of focal adhesions. These effects are mediated by the
      apolipoprotein(a) (apo(a)) component of Lp(a) since incubation of apo(a) with the
      cells evoked similar cytoskeletal rearrangements, while incubation with low
      density lipoprotein had no effect. Apo(a) also produced a time-dependent increase
      in transendothelial permeability. The cytoskeletal rearrangements evoked by
      apo(a) were abolished by C3 transferase, which inhibits Rho, and by Y-27632, an
      inhibitor of Rho kinase. In addition to actin cytoskeleton remodeling, apo(a) was
      found to cause VE-cadherin disruption and focal adhesion molecule reorganization
      in a Rho- and Rho kinase-dependent manner. Cell-cell contacts were found to be
      regulated by Rho and Rac but not Cdc42. Apo(a) caused a transient increase in the
      extent of myosin light chain phosphorylation. Finally apo(a) did not evoke
      increases in intracellular calcium levels, although the effects of apo(a) on the
      cytoskeleton were found to be calcium-dependent. We conclude that the apo(a)
      component of Lp(a) activates a Rho/Rho kinase-dependent intracellular signaling
      cascade that results in increased myosin light chain phosphorylation with
      attendant rearrangements of the actin cytoskeleton. We propose that the resultant
      increase in endothelial permeability caused by Lp(a) may help explain the
      atherosclerotic risk posed by elevated concentrations of this lipoprotein.

PMID- 14660656
TI  - Comparative vibrational spectroscopy of intracellular tau and extracellular
      collagen I reveals parallels of gelation and fibrillar structure.
AB  - The N-terminal tau 2-19 peptide undergoes gelation, syneresis, and aggregation
      over a period of years. These changes may be approximated on a shorter time scale
      by agitation and partial dehydration. The anomalously enhanced (229 nm)
      ultraviolet resonance Raman (UVRR) imide II band reveals a common structural
      feature for gels of nondehydrated tau 2-19 and collagen I and insoluble paired
      helical filaments (PHFs) and collagen I of weak hydrogen bonding at proline
      carbonyls. Anomalous UVRR enhancement of amide bands at 229 nm results from gel
      structure, as demonstrated by increased amide absorption at the red edge for tau
      2-19 gel and implies the involvement of water in gel structure. In aged,
      dehydrated tau 2-19 gel, proline carbonyls lose their bonds to water and tyrosine
      becomes deprotonated, as demonstrated by UVRR spectroscopy. The Fourier transform
      infrared (FTIR) amide I band shows that antiparallel beta-sheet structure
      increases with syneresis in the tau 2-19 hydrogel. The comparison of FTIR results
      for PHFs with collagen I gel and polyproline demonstrates that the secondary
      structure of PHFs is polyproline II. One implication of this assignment is that
      the fibrillation of hydrophilic tau is thermodynamically driven by the entropy
      gained as hydrogen-bonded water is freed, as for collagen I. The FTIR results
      also show that peptide domains culled from a longer protein do not necessarily
      fold into identical secondary structures. A pathological, sequential mechanism of
      gelation, syneresis, and fibrillation for tau in AD is suggested and is supported
      by the observation of amorphous neurofibrillary tangle development and
      fibrillation in vivo.

PMID- 14660655
TI  - 2'-benzoyloxycinnamaldehyde induces apoptosis in human carcinoma via reactive
      oxygen species.
AB  - 2'-hydroxycinnamaldehyde (HCA) has been shown to have inhibitory effects on
      farnesyl protein transferase in vitro, angiogenesis, and tumor cell growth.
      However, mechanism for these inhibitions remains unknown. As a derivative of HCA,
      BCA (2'-benzoyl-oxycinnamaldehyde) was synthesized by replacing hydroxyl group
      with benzoyl-oxyl group. When p53-mutated cancer cell lines (MDA-MB-231 breast
      cancer cell and SW620 colon cancer cell) were treated with 10 microM HCA or BCA,
      it induced growth arrest and apoptosis of tumor cells. Markers of apoptosis such
      as degradations of chromosomal DNA and poly(ADP-ribose) polymerase and activation
      of caspase-3 were detected after HCA or BCA treatment. BCA-induced apoptosis was
      blocked by pretreatment of cells with anti-oxidants, glutathione, or N-acetyl
      cysteine. In addition, BCA-induced activation of caspase-3 and degradation of
      poly(ADP-ribose) polymerase were abolished by pretreatment of cells with the anti
      oxidants. These results suggest that reactive oxygen species are major regulator
      of BCA-induced apoptosis. HCA or BCA-induced accumulation of reactive oxygen
      species was detected by using DCF-DA, an intracellular probe of oxidative stress.
      Furthermore, when BCA (100 mg/kg) was administrated intraperitoneally or orally
      into a nude mouse, it inhibited >88 or 41% of tumor growth, respectively, without
      any detectable weight change. These results suggest that BCA is a good drug
      candidate for cancer therapy.

PMID- 14660657
TI  - STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25
      locus.
AB  - Signal transducer and activator of transcription 4 (STAT4) is a critical mediator
      of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite
      extensive analysis of the immune responses of STAT4-deficient mice, there is
      still very little understood about STAT4-dependent gene induction. IL-12
      stimulated increases in IL-2 receptor alpha chain gene (CD25) mRNA levels and
      surface expression require STAT4. In this report, we utilize chromatin
      immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent
      changes in chromatin remodeling of the CD25 gene. Gene activation requires
      binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of
      the CREB-binding protein (CBP), and chromatin remodeling including increased
      acetylation and decreased methylation of histones within the CD25 promoter.
      Evidence suggests that STAT4 also facilitates binding of other factors to the
      CD25 promoter including c-Jun. Thus, these results provide a model for STAT4
      dependent gene induction and a mechanism for cytokine-induced expression of the
      CD25 gene.

PMID- 14660658
TI  - Structure and sequence determinants required for the RNA editing of ADAR2
      substrates.
AB  - ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the
      editing of mammalian RNAs by the site-specific conversion of adenosine to
      inosine. We have demonstrated previously that ADAR2 can modify its own pre-mRNA,
      leading to the creation of a proximal 3'-splice junction containing a non
      canonical adenosine-inosine (A-I) dinucleotide. Alternative splicing to this
      proximal acceptor shifts the reading frame of the mature mRNA transcript,
      resulting in the loss of functional ADAR2 expression. Both evolutionary sequence
      conservation and mutational analysis support the existence of an extended RNA
      duplex within the ADAR2 pre-mRNA formed by base-pairing interactions between
      regions approximately 1.3-kilobases apart in intron 4 and exon 5.
      Characterization of ADAR2 pre-mRNA transcripts isolated from adult rat brain
      identified 16 editing sites within this duplex region, and sites preferentially
      modified by ADAR1 and ADAR2 have been defined using both tissue culture and in
      vitro editing systems. Statistical analysis of nucleotide sequences surrounding
      edited and non-edited adenosine residues have identified a nucleotide sequence
      bias correlating with ADAR2 site preference and editing efficiency. Among a mixed
      population of ADAR substrates, ADAR2 preferentially favors its own transcript,
      yet mutation of a poor substrate to conform to the defined nucleotide bias
      increases the ability of that substrate to be modified by ADAR2. These data
      suggest that both sequence and structural elements are required to define
      adenosine moieties targeted for specific ADAR2-mediated deamination.

PMID- 14660659
TI  - The membrane domains occupied by glycosylphosphatidylinositol-anchored prion
      protein and Thy-1 differ in lipid composition.
AB  - Glycosylphosphatidylinositol-anchored prion protein and Thy-1, found in adjacent
      microdomains or "rafts" on the neuronal surface, traffic very differently and
      show distinctive differences in their resistance to detergent solubilization.
      Monovalent immunogold labeling showed that the two proteins were largely
      clustered in separate domains on the neuronal surface: 86% of prion protein was
      clustered in domains containing no Thy-1, although 40% of Thy-1 had a few
      molecules of prion protein associated with it. Only 1% of all clusters contained
      appreciable levels of both proteins (</=3 immunogold label for both). In keeping
      with this distribution, immunoaffinity isolation of detergent-resistant membranes
      (DRMs) using the non-ionic detergent Brij 96 yielded prion protein DRMs with
      little Thy-1, whereas Thy-1 DRMs contained approximately 20% of prion protein.
      The lipid content of prion protein and Thy-1 DRMs was measured by quantitative
      nano-electrospray ionization tandem mass spectrometry. In four independent
      preparations, the lipid content was highly reproducible, with Thy-1 and prion
      protein DRMs differing markedly from each other and from the total DRM pool from
      which they were immunoprecipitated. Prion protein DRMs contained significantly
      more unsaturated, longer chain lipids than Thy-1 DRMs and had 5-fold higher
      levels of hexosylceramide. The different lipid compositions are in keeping with
      the different trafficking dynamics and solubility of the two proteins and show
      that, under the conditions used, DRMs can isolate individual membrane
      microenvironments. These results further identify unsaturation and glycosylation
      of lipids as major sources of diversity of raft structure.

PMID- 14660660
TI  - Critical role for lysine 133 in the nuclear ubiquitin-mediated degradation of
      MyoD.
AB  - The ubiquitin-proteasome system is responsible for the regulation and turnover of
      the nuclear transcription factor MyoD. The degradation of MyoD can occur via an
      NH2 terminus-dependent pathway or a lysine-dependent pathway, suggesting that
      MyoD ubiquitination may be driven by different mechanisms. To understand this
      process, deletion analysis was used to identify the region of MyoD that is
      required for rapid proteolysis in the lysine-dependent pathway. Here we report
      that the basic helix-loop-helix domain is required for ubiquitination and lysine
      dependent degradation of MyoD in the nucleus. Site-directed mutagenesis in MyoD
      revealed that lysine 133 is the major internal lysine of ubiquitination. The half
      life of the MyoD K133R mutant protein was longer than that of wild type MyoD,
      substantiating the implication of lysine 133 in the turnover of MyoD in
      myoblasts. In addition, the MyoD K133R mutant displayed activity 2-3-fold higher
      than the wild type in transactivation muscle-specific gene and myogenic
      conversion of 10T1/2 cells. Taken together, our data demonstrate that lysine 133
      is targeted for ubiquitination and rapid degradation of MyoD in the lysine
      dependent pathway and plays an integral role in compromising MyoD activity in the
      nucleus.

PMID- 14660661
TI  - Biologically active decorin is a monomer in solution.
AB  - It has been reported that decorin and its protein core can have molecular masses
      nearly double the size of those previously published, suggesting a dimeric
      structure. In this study we tested whether biologically active decorin and its
      glycoprotein core would form dimers in solution. We used homo- and hetero
      bifunctional chemical cross-linking reagents, BS3 and sulfo-SMPB, respectively,
      as well as glutaraldehyde and found no preferential dimer formation, whether
      chemical cross-linking was performed in the presence or absence of live cells.
      Under the same experimental conditions, we easily detected dimers of epidermal
      growth factor receptor and basic fibroblast growth factor, two glycoproteins
      known to dimerize. Only at very high cross-linker to decorin molar ratios
      (2000:1) were trimers and multimers observed, but performing the chemical cross
      linking in the presence of a reducing agent abolished these. The elution of
      decorin protein core in Superose 6 gel chromatography gave masses compatible with
      monomeric proteins, both before and after denaturation with 2.5 M guanidine HCl.
      Matrix-assisted laser desorption ionization gave a mass of 44,077 Da for decorin
      protein core, without any evidence of dimers or oligomers. Extensive
      oligomerization of the decorin protein core was observed only after dialysis
      against water and freeze-drying. These oligomers were considered artifacts
      because they were independent of chemical cross-linking and were resistant to
      heat denaturation and disulfide-bond reduction. Oligomeric preparations showed
      markedly reduced biological activity in both phosphorylation and collagen
      fibrillogenesis assays. Thus, biologically active decorin is a monomer in
      solution and, as such, is a monovalent ligand for various extracellular matrix
      proteins, growth factors, and cell surface receptors.

PMID- 14660662
TI  - Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver
      demonstrates an essential role of selenoproteins in liver function.
AB  - Selenium is essential in mammalian embryonic development. However, in adults,
      selenoprotein levels in several organs including liver can be substantially
      reduced by selenium deficiency without any apparent change in phenotype. To
      address the role of selenoproteins in liver function, mice homozygous for a
      floxed allele encoding the selenocysteine (Sec) tRNA([Ser]Sec) gene were crossed
      with transgenic mice carrying the Cre recombinase under the control of the
      albumin promoter that expresses the recombinase specifically in liver.
      Recombination was nearly complete in mice 3 weeks of age, whereas liver
      selenoprotein synthesis was virtually absent, which correlated with the loss of
      Sec tRNA([Ser]Sec) and activities of major selenoproteins. Total liver selenium
      was dramatically decreased, whereas levels of low molecular weight
      selenocompounds were little affected. Plasma selenoprotein P levels were reduced
      by about 75%, suggesting that selenoprotein P is primarily exported from the
      liver. Glutathione S-transferase levels were elevated in the selenoprotein
      deficient liver, suggesting a compensatory activation of this detoxification
      program. Mice appeared normal until about 24 h before death. Most animals died
      between 1 and 3 months of age. Death appeared to be due to severe hepatocellular
      degeneration and necrosis with concomitant necrosis of peritoneal and
      retroperitoneal fat. These studies revealed an essential role of selenoproteins
      in liver function.

PMID- 14660663
TI  - Molecular determinants of Na+/Ca2+ exchange (NCX1) inhibition by SEA0400.
AB  - SEA0400 is a potent and selective Na(+)/Ca(2+) exchanger (NCX) inhibitor. We
      evaluated the inhibitory effects of SEA0400 on Na(+)(i)-dependent (45)Ca(2+)
      uptake and whole-cell Na(+)/Ca(2+) exchange currents in NCX-transfected
      fibroblasts. SEA0400 preferentially inhibited (45)Ca(2+) uptake by NCX1 compared
      with inhibitions by NCX2, NCX3, and NCKX2. SEA0400 also selectively blocked
      outward exchange currents from NCX1 transfectants. We searched for regions that
      may form the SEA0400 receptor in the NCX1 molecule by NCX1/NCX3 chimeric
      analysis. The results suggest that the first intracellular loop and the fifth
      transmembrane segment are mostly responsible for the differential drug responses
      between NCX1 and NCX3. Further site-directed mutagenesis revealed that multiple
      mutations at Phe-213 markedly reduced sensitivity to SEA0400 without affecting
      that to KB-R7943. We also found that Gly-833-to-Cys mutation (within the alpha-2
      repeat) greatly reduced the inhibition by SEA0400, but unexpectedly the NCX1
      chimera with an alpha-2 repeat from NCKX2 possessed normal drug sensitivity. In
      addition, exchangers with mutated exchanger inhibitory peptide regions, which
      display either undetectable or accelerated Na(+)-dependent inactivation, had a
      markedly reduced sensitivity or hypersensitivity to SEA0400, respectively. To
      verify the efficacy of the NCX inhibitor, we examined the renoprotective effect
      of SEA0400 in a hypoxic injury model using porcine renal tubular cells. SEA0400
      protected against hypoxia/reoxygenation-induced cell damage in tubular cells
      expressing wild-type NCX1 but not in cells expressing SEA0400-insensitive
      mutants. These results suggest that Phe-213, Gly-833, and residues that eliminate
      Na(+)-dependent inactivation are critical determinants for the inhibition by
      SEA0400, and their mutants are very useful for checking the pharmacological
      importance of NCX inhibition by SEA0400.

PMID- 14660664
TI  - The NMR structure of dematin headpiece reveals a dynamic loop that is
      conformationally altered upon phosphorylation at a distal site.
AB  - Dematin (band 4.9) is found in the junctional complex of the spectrin
      cytoskeleton that supports the erythrocyte cell membrane. Dematin is a member of
      the larger class of cytoskeleton-associated proteins that contain a modular
      "headpiece" domain at their extreme C termini. The dematin headpiece domain
      provides the second F-actin-binding site required for in vitro F-actin bundling.
      The dematin headpiece is found in two forms in the cell, one of 68 residues (DHP)
      and one containing a 22-amino acid insert near its N terminus (DHP+22). In
      addition, dematin contains the only headpiece domain that is phosphorylated, in
      vivo. The 22-amino acid insert in DHP+22 appeared unstructured in NMR spectra;
      therefore, we have determined the three-dimensional structure of DHP by
      multidimensional NMR methods. Although the overall three-dimensional structure of
      DHP is similar to that of the villin headpiece, there are two novel
      characteristics revealed by this structure. First, unlike villin headpiece that
      contains a single buried salt bridge, DHP contains a buried charged cluster
      comprising residues Glu(39), Arg(66), Lys(70), and the C-terminal carboxylate of
      Phe(76). Second, (15)N relaxation experiments indicate that the longer "variable
      loop" region near the N terminus of DHP (residues 20-29) is dynamic, undergoing
      significantly greater motions that the rest of the structure. Furthermore, NMR
      chemical shift changes indicate that the conformation of the dynamic variable
      loop is altered by phosphorylation of serine 74, which is far in the sequence
      from the variable loop region. Our results suggest that phosphorylation of the
      dematin headpiece acts as a conformational switch within this headpiece domain.

PMID- 14660665
TI  - Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis
      screen.
AB  - The EphA3 receptor tyrosine kinase preferentially binds ephrin-A5, a member of
      the corresponding subfamily of membrane-associated ligands. Their interaction
      regulates critical cell communication functions in normal development and may
      play a role in neoplasia. Here we describe a random mutagenesis approach, which
      we employed to study the molecular determinants of the EphA3/ephrin-A5
      recognition. Selection and functional characterization of EphA3 point mutants
      with impaired ephrin-A5 binding from a yeast expression library defined three
      EphA3 surface areas that are essential for the EphA3/ephrin-A5 interaction. Two
      of these map to regions identified previously in the crystal structure of the
      homologous EphB2-ephrin-B2 complex as potential ligand/receptor interfaces. In
      addition, we identify a third EphA3/ephrin-A5 interface that falls outside the
      structurally characterized interaction domains. Functional analysis of EphA3
      mutants reveals that all three Eph/ephrin contact areas are essential for the
      assembly of signaling-competent, oligomeric receptor-ligand complexes.

PMID- 14660666
TI  - Thermal stability and aggregation of sulfolobus solfataricus beta-glycosidase are
      dependent upon the N-epsilon-methylation of specific lysyl residues: critical
      role of in vivo post-translational modifications.
AB  - Methylation in vivo is a post-translational modification observed in several
      organisms belonging to eucarya, bacteria, and archaea. Although important
      implications of this modification have been demonstrated in several eucaryotes,
      its biological role in hyperthermophilic archaea is far from being understood.
      The aim of this work is to clarify some effects of methylation on the properties
      of beta-glycosidase from Sulfolobus solfataricus, by a structural comparison
      between the native, methylated protein and its unmethylated counterpart,
      recombinantly expressed in Escherichia coli. Analysis by Fourier transform
      infrared spectroscopy indicated similar secondary structure contents for the two
      forms of the protein. However, the study of temperature perturbation by Fourier
      transform infrared spectroscopy and turbidimetry evidenced denaturation and
      aggregation events more pronounced in recombinant than in native beta
      glycosidase. Red Nile fluorescence analysis revealed significant differences of
      surface hydrophobicity between the two forms of the protein. Unlike the native
      enzyme, which dissociated into SDS-resistant dimers upon exposure to the
      detergent, the recombinant enzyme partially dissociated into monomers. By
      electrospray mapping, the methylation sites of the native protein were
      identified. A computational analysis of beta-glycosidase three-dimensional
      structure and comparisons with other proteins from S. solfataricus revealed
      analogies in the localization of methylation sites in terms of secondary
      structural elements and overall topology. These observations suggest a role for
      the methylation of lysyl residues, located in selected domains, in the thermal
      stabilization of beta-glycosidase from S. solfataricus.

PMID- 14660667
TI  - Factor Va is inactivated by activated protein C in the absence of cleavage sites
      at Arg-306, Arg-506, and Arg-679.
AB  - Activated protein C (APC) exerts its anticoagulant activity via proteolytic
      degradation of the heavy chains of activated factor VIII (FVIIIa) and activated
      factor V (FVa). So far, three APC cleavage sites have been identified in the
      heavy chain of FVa: Arg-306, Arg-506, and Arg-679. To obtain more insight in the
      structural and functional implications of each individual cleavage, recombinant
      factor V (rFV) mutants were constructed in which two or three of the APC cleavage
      sites were mutated. After expression in COS-1 cells, rFV mutants were purified,
      activated with thrombin, and inactivated by APC. During this study we observed
      that activated rFV-GQA (rFVa-GQA), in which the arginines at positions 306, 506,
      and 679 were replaced by glycine, glutamine, and alanine, respectively, was still
      inactivated by APC. Further analysis showed that the inactivation of rFVa-GQA by
      APC was phospholipid-dependent and sensitive to an inhibitory monoclonal antibody
      against protein C. Inactivation proceeded via a rapid phase (kx1=5.4 x 10(4) M(
      1) s(-1)) and a slow phase (kx2=3.2 x 10(3) M(-1) s(-1)). Analysis of the
      inactivation curves showed that the rapid phase yielded a reaction intermediate
      that retained approximately 80% of the original FVa activity, whereas the slow
      cleavage resulted in formation of a completely inactive reaction product.
      Inactivation of rFVa-GQA was accelerated by protein S, most likely via
      stimulation of the slow phase. Immunoblot analysis using a monoclonal antibody
      recognizing an epitope between Arg-306 and Arg-506 indicated that during the
      rapid phase of inactivation a fragment of 80 kDa was generated that resulted from
      cleavage at a residue very close to Arg-506. The slow phase was associated with
      the formation of fragments resulting from cleavage at a residue 1.5-2 kDa
      carboxyl-terminal to Arg-306. Our observations may explain the unexpectedly mild
      APC resistance associated with mutations at Arg-306 (FV HongKong and FV
      Cambridge) in the heavy chain of FV.

PMID- 14660668
TI  - Involvement of IRAK-M in peptidoglycan-induced tolerance in macrophages.
AB  - The molecular mechanisms by which pathogen-associated molecular patterns
      recognized by TLR2, such as peptidoglycan (PGN), induce homotolerance are largely
      unknown. It was recently reported that IRAK-M negatively regulates TLR signaling.
      In this study, we elucidate the molecular mechanisms of tolerance induced by PGN,
      with a focus on the role of IRAK-M. We demonstrate that pretreatment of
      macrophage RAW264.7 cells with a high concentration (30 microg/ml) of PGN for 16
      h effectively induces tolerance against following stimulation with 30 microg/ml
      of PGN; while pretreatment with a low concentration (1 microg/ml) of PGN does
      not. IRAK-M is induced in cells treated with the high concentration of PGN 4-24 h
      after PGN stimulation, but not in cells treated with the low concentration of PGN
      up to 24 h after stimulation. Phosphorylation of MAPKs and IkappaBalpha is
      inhibited after the second PGN stimulation in tolerant cells. Kinase activity of
      IRAK-1 and association between IRAK-1 and MyD88 are also suppressed in PGN
      induced tolerant cells. Furthermore, down-regulation of IRAK-M expression by
      small interfering RNAs specific for IRAK-M reinstates the production of TNF-alpha
      after PGN restimulation. These results suggest that induction of IRAK-M and
      inhibition of kinase activity of IRAK-1 are crucial to PGN-induced tolerance in
      macrophages.

PMID- 14660669
TI  - Lipopolysaccharide 3-deoxy-D-manno-octulosonic acid (Kdo) core determines
      bacterial association of secreted toxins.
AB  - In contrast to cholera toxin (CT), which is secreted solubly by Vibrio cholerae
      across the outer membrane, heat-labile enterotoxin (LT) is retained on the
      surface of enterotoxigenic Escherichia coli (ETEC) via an interaction with
      lipopolysaccharide (LPS). We examined the nature of the association between LT
      and LPS. Soluble LT binds to the surface of LPS deep-rough biosynthesis mutants
      but not to lipid A, indicating that only the Kdo (3-deoxy-d-manno-octulosonic
      acid) core is required for binding. Although capable of binding truncated LPS and
      Kdo, LT has a higher affinity for longer, more complete LPS species. A putative
      LPS binding pocket is proposed based on the crystal structure of the toxin. The
      ability to bind LPS and remain associated with the bacterial surface is not
      unique to LT, as CT also binds to E. coli LPS. However, neither LT nor CT is
      capable of binding to the surface of Vibrio. The core structures of Vibrio and E.
      coli LPS differ in that Vibrio contains a phosphorylated single Kdo-lipid A, and
      E. coli LPS contains unphosphorylated Kdo2-lipid A. We determined that the
      phosphate group on the Kdo core of Vibrio LPS prevents CT from binding, resulting
      in the secretion of soluble toxin. Because LT binds E. coli LPS, it remains
      associated with the extracellular bacterial surface and is released in
      association with outer membrane vesicles. We propose that difference in the
      extracellular fates of LT and CT contribute to the differences in disease caused
      by ETEC and Vibrio cholerae.

PMID- 14660670
TI  - Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1.
AB  - The 8p11 myeloproliferative syndrome is an aggressive disorder caused by FGFR1
      fusion proteins resulting from a subset of acquired translocations that target
      chromosome band 8p11. These chimeric proteins have constitutive FGFR1 tyrosine
      kinase activity and are believed to deregulate hemopoietic development in a
      manner analogous to BCR-ABL in chronic myeloid leukemia. Here we have studied the
      role of STAT proteins in transformation mediated by the most common of these
      fusions, ZNF198-FGFR1. We found that STATs 1, 3, and 5 were activated
      constitutively in ZNF198-FGFR1-transformed Ba/F3 cells and that STATs 2, 4, and 6
      were also tyrosine-phosphorylated. Induction of dominant negative STAT mutants
      showed that activation of STAT5, but not STATs 1 or 3, was essential for the anti
      apoptotic effect of ZNF198-FGFR1 and that STAT5 activation is essential for the
      elevated levels of BclXL in transformed cells. STAT5 activation was also shown to
      be required for continued cell cycle progression of BaF3/ZNF198-FGFR1 cells in
      conditions of cytokine deprivation and for up-regulation of the DNA repair
      protein Rad51. These findings suggest a critical role of STAT5 activation in
      transformation mediated by ZNF198-FGFR1.

PMID- 14660671
TI  - entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse.
AB  - entla (ent) is a novel recessive phenotype of mice. The underlying mutation was
      mapped to chromosome 9 (60.1 centimorgans) and identified as an allele of the
      Cacna2d2 gene encoding the alpha2delta-2 subunit of voltage-gated calcium
      channels. The Cacna2d2entla allele harbors a 38-kb duplication comprising the 117
      nucleotides of exon 3. The predicted duplication of 39 amino acid residues near
      the subunit's N terminus results in the expression of a full-length, membrane
      associated protein. Western blot data were consistent with correct cleavage of
      the alpha2delta-2entla precursor into alpha2entla and delta2 proteins but
      indicated loss of the disulfide linkage between the two proteins. ent/ent mice
      develop ataxia by postnatal day 13-15, followed by paroxysmal dyskinesia a few
      days later. Two distinct types of cortical and hippocampal epileptic activity at
      2 and 4 Hz were recorded, indicative of absence epilepsy. Homozygotes display
      reduced size and weight, increased mortality before weaning, and female
      infertility. No overt neuroanatomical abnormalities were detected. Ca2+ current
      densities recorded from acutely dissociated Purkinje cells of homozygous entla
      animals were reduced by 50% compared with wild type. Ligand binding assays using
      the antiepileptic drug [3H]gabapentin, a specific ligand of the alpha2delta-1 and
      alpha2delta-2 subunits, revealed a >60% reduced maximum binding to cerebellar
      membranes of ent/ent compared with unaffected littermates. entla is allelic to
      ducky and ducky2J, representing the third murine Cacna2d2 allele identified and
      so far the only one encoding an untruncated protein that is incorporated into
      membranes.

PMID- 14660672
TI  - Role of lipid microdomains in P/Q-type calcium channel (Cav2.1) clustering and
      function in presynaptic membranes.
AB  - Lipid microdomains can selectively include or exclude proteins and may be
      important in a variety of functions such as protein sorting, cell signaling, and
      synaptic transmission. The present study demonstrates that two different voltage
      gated calcium channels, which both interact with soluble N-ethyl-maleimide
      sensitive fusion protein attachment protein receptor (SNARE) proteins but have
      distinct subcellular distributions and roles in synaptic transmission, are
      differently distributed in lipid microdomains; presynaptic P/Q (Cav2.1) but not
      Lc (Cav1.2) calcium channel subtypes are mainly accumulated in detergent
      insoluble complexes. The immunoisolation of multiprotein complexes from detergent
      insoluble or detergent-soluble fractions shows that the alpha1A subunits of
      Cav2.1 colocalize and interact with SNARE complexes in lipid microdomains. The
      altered organization of these microdomains caused by saponin and methyl-beta
      cyclodextrin treatment largely impairs the buoyancy and distribution of Cav2.1
      channels and SNAREs in flotation gradients. On the other hand, cholesterol
      reloading partially reverses the drug effects. Methyl-beta-cyclodextrin treatment
      alters the colocalization of Cav2.1 with the proteins of the exocytic machinery
      and also impairs calcium influx in nerve terminals. These results show that lipid
      microdomains in presynaptic terminals are important in organizing membrane sites
      specialized for synaptic vesicle exocytosis. The cholesterol-enriched
      microdomains contribute to optimizing the compartmentalization of exocytic
      machinery and the calcium influx that triggers synaptic vesicle exocytosis.

PMID- 14660673
TI  - The amino-terminal portion of the F-box protein Met30p mediates its nuclear
      import and assimilation into an SCF complex.
AB  - SCF complexes are a conserved family of ubiquitin ligases composed of a common
      core of components and a variable component called an F-box protein that defines
      substrate specificity. The F-box motif links the F-box protein to the core
      components via its interaction with Skp1p. In yeast, the SCFMet30p complex
      contains the Met30p F-box protein and regulates Met4p, a transcription factor
      that mediates sulfur fixation and methionine biosynthesis. Although a nuclear
      protein, Met30p lacks a definable nuclear localization sequence. Here we show
      that the entire amino-terminal half of Met30p is required for its proper nuclear
      localization. Mutations in the F-box, but not mutations in Skp1p, affect Met30p
      nuclear localization, indicating that the F-box motif plays an important role in
      Met30p trafficking independent of its interaction with Skp1p binding. Met30p
      mutants that poorly localize to the nucleus display increased nuclear to
      cytoplasmic exchange, indicating that the amino terminus mediates nuclear
      retention in addition to nuclear import. The Met30p F-box motif, residues 180
      225, is necessary and sufficient to bind Skp1p; however, mutations upstream of
      the Met30p F-box inhibit Skp1p binding. We propose that additional factors bind
      the amino-terminal region of Met30p and mediate its nuclear localization and
      assimilation into an SCF complex.

PMID- 14660674
TI  - Identification and molecular characterization of the beta-ketoacyl-[acyl carrier
      protein] synthase component of the Arabidopsis mitochondrial fatty acid synthase.
AB  - Substrate specificity of condensing enzymes is a predominant factor determining
      the nature of fatty acyl chains synthesized by type II fatty acid synthase (FAS)
      enzyme complexes composed of discrete enzymes. The gene (mtKAS) encoding the
      condensing enzyme, beta-ketoacyl-[acyl carrier protein] (ACP) synthase (KAS),
      constituent of the mitochondrial FAS was cloned from Arabidopsis thaliana, and
      its product was purified and characterized. The mtKAS cDNA complemented the KAS
      II defect in the E. coli CY244 strain mutated in both fabB and fabF encoding KAS
      I and KAS II, respectively, demonstrating its ability to catalyze the
      condensation reaction in fatty acid synthesis. In vitro assays using extracts of
      CY244 containing all E. coli FAS components, except that KAS I and II were
      replaced by mtKAS, gave C(4)-C(18) fatty acids exhibiting a bimodal distribution
      with peaks at C(8) and C(14)-C(16). Previously observed bimodal distributions
      obtained using mitochondrial extracts appear attributable to the mtKAS enzyme in
      the extracts. Although the mtKAS sequence is most similar to that of bacterial
      KAS IIs, sensitivity of mtKAS to the antibiotic cerulenin resembles that of E.
      coli KAS I. In the first or priming condensation reaction of de novo fatty acid
      synthesis, purified His-tagged mtKAS efficiently utilized malonyl-ACP, but not
      acetyl-CoA as primer substrate. Intracellular targeting using green fluorescent
      protein, Western blot, and deletion analyses identified an N-terminal signal
      conveying mtKAS into mitochondria. Thus, mtKAS with its broad chain length
      specificity accomplishes all condensation steps in mitochondrial fatty acid
      synthesis, whereas in plastids three KAS enzymes are required.

PMID- 14660675
TI  - bcl-2 induction of urokinase plasminogen activator receptor expression in human
      cancer cells through Sp1 activation: involvement of ERK1/ERK2 activity.
AB  - We have previously demonstrated that Bcl-2 overexpression in human breast
      carcinoma and melanoma cells synergizes with hypoxia to increase angiogenesis
      through up-regulation of vascular endothelial growth factor. In this work we
      demonstrated, for the first time, that Bcl-2 overexpression in cancer cells
      exposed to hypoxia modulates urokinase plasminogen activator receptor (uPAR)
      expression through Sp1 transcription factor and that the extracellular signal
      regulated kinase (ERK) pathway plays a role in Sp1 transcriptional activity. In
      particular, an increase in uPAR protein and mRNA expression was found in melanoma
      bcl-2 transfectants grown under hypoxia when compared with control cells, and a
      decrease of uPAR protein expression was induced by treatment of cells with
      specific bcl-2 antisense oligonucleotides. Up-regulation of uPAR expression was
      accompanied by increased Sp1 protein expression, stability, serine
      phosphorylation, and DNA binding activity. Treatment of cells with mitramycin A,
      an inhibitor of Sp1 activity, confirmed the role of Sp1 transcriptional activity
      in uPAR induction by Bcl-2. The contribution of the ERK pathway in Sp1-increased
      transcriptional activity was demonstrated by the use of chemical inhibition. In
      fact, ERK kinase activation was induced in Bcl-2-overexpressing cells exposed to
      hypoxia, and the ERK kinase inhibitor UO126 was able to down-regulate Sp1
      phosphorylation and DNA binding activity. Using a human breast carcinoma line, we
      obtained data supporting our findings with melanoma cells and identified a link
      between the induction of Sp1 and uPAR expression as a common bcl-2-controlled
      phenomenon in human tumors. In conclusion, our results strongly indicate that up
      regulation of uPAR expression by Bcl-2 in hypoxia is modulated by Sp1 DNA binding
      activity through the ERK signaling pathway.

PMID- 14660676
TI  - Combinatorial control of DNase I-hypersensitive site formation and erasure by
      immunoglobulin heavy chain enhancer-binding proteins.
AB  - DNase I-hypersensitive sites in cellular chromatin are usually believed to be
      nucleosome-free regions generated by transcription factor binding. Using a cell
      free system we show that hypersensitivity does not simply correlate with the
      number of DNA-bound proteins. Specifically, the leucine zipper containing basic
      helix-loop-helix protein TFE3 was sufficient to induce a DNase I-hypersensitive
      site at the immunoglobulin heavy chain micro enhancer in vitro. TFE3 enhanced
      binding of an ETS protein PU.1 to the enhancer. However, PU.1 binding erased the
      DNase I-hypersensitive site without abolishing TFE3 binding. Furthermore, TFE3
      binding enhanced transcription in the presence and absence of a hypersensitive
      site, whereas endonuclease accessibility correlated strictly with DNase I
      hypersensitivity. We infer that chromatin constraints for transcription and
      nuclease sensitivity can differ.

PMID- 14660677
TI  - A permissive role for phosphatidylinositol 3-kinase in the Stat5-mediated
      expression of cyclin D2 by the interleukin-2 receptor.
AB  - The interleukin-2 (IL-2) receptor promotes T cell proliferation in part by
      inducing the expression of D-type cyclins, which enable cells to progress from
      the G1 to S phase of the cell cycle. We previously showed that the IL-2 receptor
      induces expression of cyclin D2 by activating the transcription factor Stat5,
      which binds directly and immediately to a site upstream of the cyclin D2
      promoter. We show here that subsequent transcription of the cyclin D2 gene occurs
      by a delayed, cycloheximide-sensitive mechanism, which implies the involvement of
      additional regulatory mechanisms. The transcription factor c-Myc is induced by
      Stat5 and is reported to bind to two E box motifs in the cyclin D2 promoter.
      However, in IL-2-stimulated T cells, c-Myc does not appear to be involved in
      cyclin D2 induction, since we found that these two E boxes are preferentially
      bound by USF-1 and USF-2 and, moreover, are dispensable for cyclin D2 promoter
      activity. Instead, we found that Stat5 activates the phosphatidylinositol 3
      kinase (PI3 kinase) pathway by a delayed, cycloheximide-sensitive mechanism and
      that PI3 kinase activity is essential for the induction of cyclin D2 by Stat5.
      Chromatin immunoprecipitation experiments revealed that PI3 kinase is required
      for the optimal binding of RNA polymerase II to the promoters of cyclin D2 as
      well as other genes. Our results reveal a novel link between PI3 kinase and RNA
      polymerase II promoter binding activity and demonstrate discrete, coordinated
      roles for the PI3 kinase and Stat5 pathways in cyclin D2 transcription.

PMID- 14660678
TI  - Lysine residues direct the chlorination of tyrosines in YXXK motifs of
      apolipoprotein A-I when hypochlorous acid oxidizes high density lipoprotein.
AB  - Oxidized lipoproteins may play an important role in the pathogenesis of
      atherosclerosis. Elevated levels of 3-chlorotyrosine, a specific end product of
      the reaction between hypochlorous acid (HOCl) and tyrosine residues of proteins,
      have been detected in atherosclerotic tissue. Thus, HOCl generated by the
      phagocyte enzyme myeloperoxidase represents one pathway for protein oxidation in
      humans. One important target of the myeloperoxidase pathway may be high density
      lipoprotein (HDL), which mobilizes cholesterol from artery wall cells. To
      determine whether activated phagocytes preferentially chlorinate specific sites
      in HDL, we used tandem mass spectrometry (MS/MS) to analyze apolipoprotein A-I
      that had been oxidized by HOCl. The major site of chlorination was a single
      tyrosine residue located in one of the protein's YXXK motifs (where X represents
      a nonreactive amino acid). To investigate the mechanism of chlorination, we
      exposed synthetic peptides to HOCl. The peptides encompassed the amino acid
      sequences YKXXY, YXXKY, or YXXXY. MS/MS analysis demonstrated that chlorination
      of tyrosine in the peptides that contained lysine was regioselective and occurred
      in high yield if the substrate was KXXY or YXXK. NMR and MS analyses revealed
      that the N(epsilon) amino group of lysine was initially chlorinated, which
      suggests that chloramine formation is the first step in tyrosine chlorination.
      Molecular modeling of the YXXK motif in apolipoprotein A-I demonstrated that
      these tyrosine and lysine residues are adjacent on the same face of an
      amphipathic alpha-helix. Our observations suggest that HOCl selectively targets
      tyrosine residues that are suitably juxtaposed to primary amino groups in
      proteins. This mechanism might enable phagocytes to efficiently damage proteins
      when they destroy microbial proteins during infection or damage host tissue
      during inflammation.

PMID- 14660679
TI  - Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+
      channel in insulin granule exocytosis.
AB  - ATP, cAMP, and Ca(2+) are the major signals in the regulation of insulin granule
      exocytosis in pancreatic beta cells. The sensors and regulators of these signals
      have been characterized individually. The ATP-sensitive K(+) channel, acting as
      the ATP sensor, couples cell metabolism to membrane potential. cAMP-GEFII, acting
      as a cAMP sensor, mediates cAMP-dependent, protein kinase A-independent
      exocytosis, which requires interaction with both Piccolo as a Ca(2+) sensor and
      Rim2 as a Rab3 effector. l-type voltage-dependent Ca(2+) channels (VDCCs)
      regulate Ca(2+) influx. In the present study, we demonstrate interactions of
      these molecules. Sulfonylurea receptor 1, a subunit of ATP-sensitive K(+)
      channels, interacts specifically with cAMP-GEFII through nucleotide-binding fold
      1, and the interaction is decreased by a high concentration of cAMP. Localization
      of cAMP-GEFII overlaps with that of Rim2 in plasma membrane of insulin-secreting
      MIN6 cells. Localization of Rab3 co-incides with that of Rim2. Rim2 mutant
      lacking the Rab3 binding region, when overexpressed in MIN6 cells, is localized
      exclusively in cytoplasm, and impairs cAMP-dependent exocytosis in MIN6 cells. In
      addition, Rim2 and Piccolo bind directly to the alpha(1)1.2-subunit of VDCC.
      These results indicate that ATP sensor, cAMP sensor, Ca(2+) sensor, and VDCC
      interact with each other, which further suggests that ATP, cAMP, and Ca(2+)
      signals in insulin granule exocytosis are integrated in a specialized domain of
      pancreatic beta cells to facilitate stimulus-secretion coupling.

PMID- 14660680
TI  - Mitochondria provide the main source of cytosolic ATP for activation of outward
      rectifying K+ channels in mesophyll protoplast of chlorophyll-deficient mutant
      rice (OsCHLH) seedlings.
AB  - The role of mitochondria in providing intracellular ATP that controls the
      activity of plasma membrane outward-rectifying K+ channels was evaluated. The
      OsCHLH rice mutant, which lacks chlorophyll in the thylakoids, was isolated by T
      DNA gene trapping (Jung, K.-H., Hur, J., Ryu, C.-H., Choi, Y., Chung, Y.-Y.,
      Miyao, A., Hirochika, H., and An, G. (2003) Plant Cell Physiol. 44, 463-472). The
      OsCHLH mutant is unable to fix CO2 and exhibits reduced growth. Wild type and
      mutant plants exhibit similar rates of respiratory O2 uptake in the dark, whereas
      the rate of photosynthetic O2 evolution by the mutant was negligible during
      illumination. During dark respiration the wild type and mutant exhibited similar
      levels of cytoplasmic ATP. In the mutant oligomycin treatment (an inhibitor of
      mitochondrial F1F0-ATPase) drastically reduced ATP production. The fact that this
      was reversed by the addition of glucose suggested that the mutant produced ATP
      exclusively from mitochondria but not from chloroplasts. In whole cell patch
      clamp experiments, the activity of outward-rectifying K+ channels of rice
      mesophyll cells showed ATP-dependent currents, which were 1.5-fold greater in
      wild type than in mutant cells. Channels in both wild type and mutant cells were
      deactivated by the removal of cytosolic ATP, whereas in the presence of ATP the
      channels remained active. We conclude that mesophyll cells in the OsCHLH rice
      mutant derive ATP from mitochondrial respiration, and that this is critical for
      the normal function of plasma membrane outward-rectifying K+ channels.

PMID- 14660681
TI  - p8 improves pancreatic response to acute pancreatitis by enhancing the expression
      of the anti-inflammatory protein pancreatitis-associated protein I.
AB  - p8 is a transcription cofactor whose expression is strongly and rapidly activated
      in pancreatic acinar cells during the acute phase of pancreatitis. A p8-deficient
      mouse strain was generated as a tool to investigate its function. Upon induction
      of acute pancreatitis, myeloperoxidase activity in pancreas and serum
      concentrations of amylase and lipase were much higher and pancreatic lesions more
      severe in p8-deficient mice than in wild-type, indicating that p8 expression
      decreased pancreatic sensitivity to pancreatitis induction. The protective
      mechanism might involve the pancreatitis-associated protein (PAP I), whose strong
      induction during pancreatitis is p8-dependent, because administration of anti-PAP
      I antibodies to rats increased pancreatic inflammation during pancreatitis. In
      addition, 100 ng/ml PAP I in the culture medium of macrophages prevented their
      activation by tumor necrosis factor alpha, strongly suggesting that PAP I was an
      anti-inflammatory factor. Finally, PAP I was able to inhibit NFkappaB activation
      by tumor necrosis factor alpha, in macrophages and in the AR42J pancreatic acinar
      cell line. In conclusion, p8 improves pancreatic resistance to inducers of acute
      pancreatitis by a mechanism implicating the expression of the anti-inflammatory
      protein PAP I.

PMID- 14660682
TI  - Origins of bidirectional promoters: computational analyses of intergenic distance
      in the human genome.
AB  - We have analyzed intergenic distances and searched for the presence of
      bidirectional genes using the complete sequences and mapping information of human
      chromosomes 20, 21, and 22, which contain 2,122 known and predicted genes.
      Intergenic distances between genes with divergent transcripts were distributed in
      a biphasic manner with a strong peak of 25 kb and a weak peak of 0.3 kb between
      the divergent transcripts, suggesting that the genes might share a common
      promoter. The weak peak was not observed at the transcriptional ends of genes.
      Seventy-three percent (55/75 pairs of genes, from a total of 150 genes) of these
      divergent transcripts located within 1 kb of one another were CpG islands.
      Expression of the divergent transcript genes was not concordant in various human
      tissues, suggesting that they were independently regulated. Analyses of the
      frequency of occurrence of interspersed repeats in the intergenic sequences
      suggested that these repeats are strongly excluded from the regions of
      transcriptional starts. This exclusion might be responsible for the existence of
      these divergent transcripts.

PMID- 14660683
TI  - Phylogenetic estimation of context-dependent substitution rates by maximum
      likelihood.
AB  - Nucleotide substitution in both coding and noncoding regions is context
      dependent, in the sense that substitution rates depend on the identity of
      neighboring bases. Context-dependent substitution has been modeled in the case of
      two sequences and an unrooted phylogenetic tree, but it has only been
      accommodated in limited ways with more general phylogenies. In this article,
      extensions are presented to standard phylogenetic models that allow for better
      handling of context-dependent substitution, yet still permit exact inference at
      reasonable computational cost. The new models improve goodness of fit
      substantially for both coding and noncoding data. Considering context dependence
      leads to much larger improvements than does using a richer substitution model or
      allowing for rate variation across sites, under the assumption of site
      independence. The observed improvements appear to derive from three separate
      properties of the models: their explicit characterization of context-dependent
      substitution within N-tuples of adjacent sites, their ability to accommodate
      overlapping N-tuples, and their rich parameterization of the substitution
      process. Parameter estimation is accomplished using an expectation maximization
      algorithm, with a quasi-Newton algorithm for the maximization step; this approach
      is shown to be preferable to ordinary Newton methods for parameter-rich models.
      Overlapping tuples are efficiently handled by assuming Markov dependence of the
      observed bases at each site on those at the N - 1 preceding sites, and the
      required conditional probabilities are computed with an extension of
      Felsenstein's algorithm. Estimated substitution rates based on a data set of
      about 160,000 noncoding sites in mammalian genomes indicate a pronounced CpG
      effect, but they also suggest a complex overall pattern of context-dependent
      substitution, comprising a variety of subtle effects. Estimates based on about 3
      million sites in coding regions demonstrate that amino acid substitution rates
      can be learned at the nucleotide level, and suggest that context effects across
      codon boundaries are significant.

PMID- 14660684
TI  - Phylogeography and origin of Indian domestic goats.
AB  - The Indian subcontinent contains 20 well-characterized goat breeds, which vary in
      their genetic potential for the production of milk, meat, and fibre; disease
      resistance; heat tolerance; and fecundity. Indian goats make up 20% of the
      world's goat population, but there has been no extensive study of these
      economically important animals. Therefore, we have undertaken the present
      investigation of 363 goats belonging to 10 different breeds from different
      geographic regions of India using mtDNA sequence data from the HVRI region. We
      find evidence for population structure and novel lineages in Indian goats and
      cannot reconcile the genetic diversity found within the major lineage with
      domestication starting 10,000 years ago from a single mtDNA ancestor. Thus, we
      propose a more complex origin for domestic goats.

PMID- 14660685
TI  - Congruent mammalian trees from mitochondrial and nuclear genes using Bayesian
      methods.
AB  - Analyses of mitochondrial and nuclear gene sequences have often produced
      different mammalian tree topologies, undermining confidence in the merit of
      molecular approaches with respect to "traditional" morphological classification.
      The recent sequencing of the complete mitochondrial genomes of two additional
      rodents (Spalax judaei and Jaculus jaculus) and one lagomorph (Ochotona princeps)
      has prompted us to reinvestigate the issue. Using Bayesian phylogenetics, we
      found phylogenetic relationships between mammalian species highly congruent with
      previous results based on nuclear genes. Our results show the existence of four
      primary lineages of placental mammals: Xenarthra, Afrotheria, Laurasiatheria, and
      Euarchontoglires. Relationships between and within these lineages strongly
      suggest that the gene trees may also be congruent with the underlying species
      phylogeny.

PMID- 14660686
TI  - A gradient of silent substitution rate in the human pseudoautosomal region.
AB  - It has been demonstrated that recombination in the human p-arm pseudoautosomal
      region (p-PAR) is at least twenty times more frequent than the genomic average of
      approximately 1 cM/Mb, which may affect substitution patterns and rates in this
      region. Here I report the analysis of substitution patterns and rates in 10
      human, chimpanzee, gorilla, and orangutan genes across the p-PAR. Between species
      silent divergence in the p-PAR forms a gradient, increasing toward the telomere.
      The correlation of silent divergence with distance from the p-PAR boundary is
      highly significant (rho = 0.911, P < 0.001). After exclusion of the CpG
      dinucleotides this correlation is still significant (rho = 0.89, P < 0.01), thus
      the substitution rate gradient cannot be explained solely by the differences in
      the extent of methylation across the p-PAR. Frequent recombination in the PAR may
      result in a relatively strong effect of biased gene conversion (BGC), which,
      because of the increased probability of fixation of the G or C nucleotides at (A
      or T)/(G or C) segregating sites, may affect substitution rates. BGC, however,
      does not seem to be the factor creating the substitution rate gradient in the p
      PAR, because the only gradient is still detactable if only A<-->T and G<-->C
      substitutions are taken into account (rho = 0.82, P < 0.01). I hypothesize that
      the substitution rate gradient in the p-PAR is due to the mutagenic effect of
      recombination, which is very frequent in the distal human p-PAR and might be
      lower near the p-PAR boundary.

PMID- 14660687
TI  - Evolution of interacting proteins in the mitochondrial electron transport system
      in a marine copepod.
AB  - The extensive interaction between mitochondrial-encoded and nuclear-encoded
      subunits of electron transport system (ETS) enzymes in mitochondria is expected
      to lead to intergenomic coadaptation. Whether this coadaptation results from
      adaptation to the environment or from fixation of deleterious mtDNA mutations
      followed by compensatory nuclear gene evolution is unknown. The intertidal
      copepod Tigriopus californicus shows extreme divergence in mtDNA sequence and
      provides an excellent model system for study of intergenomic coadaptation. Here,
      we examine genes encoding subunits of complex III of the ETS, including the mtDNA
      encoded cytochrome b (CYTB), the nuclear-encoded rieske iron-sulfur protein
      (RISP), and cytochrome c(1) (CYC1). We compare levels of polymorphism within
      populations and divergence between populations in these genes to begin to
      untangle the selective forces that have shaped evolution in these genes. CYTB
      displays dramatic divergence between populations, but sequence analysis shows no
      evidence for positive selection driving this divergence. CYC1 and RISP have lower
      levels of sequence divergence between populations than CYTB, but, again, sequence
      analysis gives no evidence for positive selection acting on them. However, an
      examination of variation at cytochrome c (CYC), a nuclear-encoded protein that
      transfers electrons between complex III and complex IV provides evidence for
      selective divergence. Hence, it appears that rapid evolution in mitochondrial
      encoded subunits is not always associated with rapid divergence in interacting
      subunits (CYC1 and RISP), but can be in some cases (CYC). Finally, a comparison
      of nuclear-encoded and mitochondrial-encoded genes from T. californicus suggests
      that substitution rates in the mitochondrial-encoded genes are dramatically
      increased relative to nuclear genes.

PMID- 14660688
TI  - Genetic variation versus recombination rate in a structured population of mice.
AB  - The correlation between genetic variation and recombination rate was investigated
      in a structured mouse population. Nucleotide sequence data from 19 autosomal DNA
      loci from eight inbred strains of mouse (Mus musculus) sampled from three major
      subspecies were analyzed. The recombination rate was estimated from the
      comparison of genetic and physical map distances between markers flanking a 10-cM
      region of each locus. The strains were categorized into four groups
      (subpopulations) based on geography. By partitioning the genetic diversity into
      within-group and among-group variation, we detected a positive correlation
      between the recombination rate and nucleotide diversity within groups. The level
      of nucleotide differentiation among groups (G(ST)) showed a negative correlation
      with the rate of recombination. There was no significant correlation between
      recombination rate and nucleotide diversity when data from different
      subpopulations were pooled. No correlation was detected between recombination
      rate and nucleotide divergence of M. musculus and M. spicilegus. These patterns
      deviate from the strict neutral expectation under the constant nucleotide
      substitution rate, and they are likely to have been formed either by a
      hitchhiking effect of positively selected mutants or by background selection of
      deleterious mutants occurring in a subdivided population. Our series of
      comparisons show that because a real population always has some structure,
      incorporation of its information is important in detecting non-neutral evolution.

PMID- 14660689
TI  - Empirical models for substitution in ribosomal RNA.
AB  - Empirical models of substitution are often used in protein sequence analysis
      because the large alphabet of amino acids requires that many parameters be
      estimated in all but the simplest parametric models. When information about
      structure is used in the analysis of substitutions in structured RNA, a similar
      situation occurs. The number of parameters necessary to adequately describe the
      substitution process increases in order to model the substitution of paired
      bases. We have developed a method to obtain substitution rate matrices
      empirically from RNA alignments that include structural information in the form
      of base pairs. Our data consisted of alignments from the European Ribosomal RNA
      Database of Bacterial and Eukaryotic Small Subunit and Large Subunit Ribosomal
      RNA ( Wuyts et al. 2001. Nucleic Acids Res. 29:175-177; Wuyts et al. 2002.
      Nucleic Acids Res. 30:183-185). Using secondary structural information, we
      converted each sequence in the alignments into a sequence over a 20-symbol code:
      one symbol for each of the four individual bases, and one symbol for each of the
      16 ordered pairs. Substitutions in the coded sequences are defined in the natural
      way, as observed changes between two sequences at any particular site. For given
      ranges (windows) of sequence divergence, we obtained substitution frequency
      matrices for the coded sequences. Using a technique originally developed for
      modeling amino acid substitutions ( Veerassamy, Smith, and Tillier. 2003. J.
      Comput. Biol. 10:997-1010), we were able to estimate the actual evolutionary
      distance for each window. The actual evolutionary distances were used to derive
      instantaneous rate matrices, and from these we selected a universal rate matrix.
      The universal rate matrices were incorporated into the Phylip Software package (
      Felsenstein 2002. http://evolution.genetics.washington.edu/phylip.html), and we
      analyzed the ribosomal RNA alignments using both distance and maximum likelihood
      methods. The empirical substitution models performed well on simulated data, and
      produced reasonable evolutionary trees for 16S ribosomal RNA sequences from
      sequenced Bacterial genomes. Empirical models have the advantage of being easily
      implemented, and the fact that the code consists of 20 symbols makes the models
      easily incorporated into existing programs for protein sequence analysis. In
      addition, the models are useful for simulating the evolution of RNA sequence and
      structure simultaneously.

PMID- 14660690
TI  - Sequential evolution of a symbiont inferred from the host: Wolbachia and
      Drosophila simulans.
AB  - This study aims to unravel the biogeography of a model symbiont/host system by
      exploiting the prediction that a symbiont will leave a signature of infection on
      the host. Specifically, a global sample of 1,442 Drosophila simulans from 33
      countries and 64 sampling localities was employed to infer the phylogeography of
      the maternally inherited alpha-proteobacteria Wolbachia. Phylogenetic analyses,
      from three symbiont genes and 24 mtDNA genomes (excluding the A + T-rich region),
      showed that each of four Wolbachia strains infected D. simulans once. The global
      distribution and abundance of the Wolbachia strains and the three mtDNA
      haplogroups (D. simulans siI, siII and siIII) was then determined. Finally,
      network analyses of variable regions within siI (584 bp from seven additional
      lines) and siII (1,701 bp from 383 lines) facilitated a detailed biogeographic
      discussion. There is little variation in siIII and the haplogroup is restricted
      in its distribution. These data show how the history of an infection can be
      mapped by combining data from the symbiont and the host. They say little about
      the organismal history of the host because the mtDNA genome is a biased
      representation of the whole genome.

PMID- 14660691
TI  - Sex differences in structure and expression of the sex chromosome genes CHD1Z and
      CHD1W in zebra finches.
AB  - Genes on the sex chromosomes are unique because of their sex-specific
      inheritance. One question is whether homologous gene pairs on the sex
      chromosomes, which have diverged in their sequence, have acquired different
      functions. We have analyzed the first homologous pair of genes (CHD1Z and CHD1W)
      discovered on the avian Z and W sex chromosomes of the zebra finch (Taeniopygia
      guttata) to examine whether functional differences may have evolved. Sequence
      analysis revealed that the two genes maintained a high degree of similarity
      especially within the C, H, and D domains, but outside of these regions larger
      differences were observed. Expression studies showed that CHD1W was unique to
      females and has the potential to produce a protein that CHD1Z does not. CHD1Z
      mRNA was expressed at a higher level in the male brain than in the female brain
      at various post-hatch ages. Reporter constructs containing the 5' flanking
      regions of each gene showed they had the ability to drive reporter expression in
      primary cell cultures. The 5' flanking region sequence of CHD1Z and CHD1W
      exhibited little homology, and differences in putative promoter elements were
      apparent. These differences between CHD1Z and CHD1W suggest that the two proteins
      may have diverged in their function.

PMID- 14660692
TI  - Inference of positive and negative selection on the 5' regulatory regions of
      Drosophila genes.
AB  - Both positive selection and negative selection have been shown to drive the
      evolution of coding regions. It is of interest to know if the corresponding 5'
      regions of genes may be subjected to selection of comparable intensities. For
      such a comparison, we chose the Accessory gland protein (Acp) genes as our test
      case. About 700 bp and 600 bp for the 5' and coding regions, respectively, of
      eight previously unstudied genes were sequenced from 21 isogenic lines of D.
      melanogaster and one line from D. simulans. The ratio of divergence at the amino
      acid replacement sites (A) over that at the synonymous sites (S) was twice the
      ratio for common polymorphism. Interestingly, the 5' region shows the same trend,
      with the 5'/S divergence ratio being 1.8 times higher than the 5'/S ratio for
      common polymorphism. There are several possible explanations for the 5'/S ratios,
      including demography, negative selection, and positive selection. Under normal
      conditions, positive selection is the most likely explanation. If that is true,
      about 45 to 50 percent of all fixed differences at both the replacement and 5'
      sites were adaptive, even though the substitution rate in the former is only half
      that of the latter (K(A)/K(S) approximately 0.3 vs. K(5')/K(S) approximately
      0.6). As previous analyses have indicated, the inclusion of slightly deleterious
      polymorphism confounds the inference of positive selection. The analysis of
      published polymorphism data covering 97 verified 5' regions of Drosophila
      suggests more pronounced selective constraint on the 5' untranslated region and
      the core promoter (together corresponding to approximately 200 bp in this data
      set) when compared to the more distal portion of the 5' region of genes.

PMID- 14660693
TI  - Evolution of developmental genes: molecular microevolution of enhancer sequences
      at the Ubx locus in Drosophila and its impact on developmental phenotypes.
AB  - Homeotic genes, which function to specify segment identity along the anterior
      posterior axis of embryos, are controlled by extensive batteries of enhancer
      sequences. We have investigated patterns of interspecific and intraspecific
      molecular variation in three enhancers of the Ultrabithorax (Ubx) locus, which
      are bx-32.8, pbx32.7, and bxd4.1, from the Drosophila melanogaster species group.
      These enhancer sequences control Ubx expression by binding to multiple
      transcription factors encoded by gap, pair-rule, and dorsoventrally expressed
      genes. Sequence comparisons reveal purifying selection acting on all three
      enhancers, both in bases binding transcription factors and in bases whose
      functions are as yet unknown. Neutrality tests largely fail to reject a neutral
      evolution model. However, using a matrix similarity value to reflect the binding
      affinity of the protein-binding sites, interspecific and intraspecific variation
      that may have potential to affect the binding affinity of the sequences
      homologous to those binding transcription factors in D. melanogaster are
      discovered, suggesting evolutionary flexibility in the way in which these
      sequences function in the control of development. As a means of measuring the
      impact of intraspecific variation on observable phenotypes, we have induced Ubx
      mutant phenocopies with embryonic ether treatment, and find strong and highly
      significant variation between D. melanogaster strains in their phenocopy
      frequencies. This variation shows no significant correlation with the strengths
      of the mutant phenotypes when the strains are heterozygous with a Ubx null
      mutation. Estimated phylogenetic trees have been constructed for the three
      enhancer regions investigated. Neither of the two phenotypic traits investigated
      shows any significant associations with the phylogeny of any of the three
      enhancers.

PMID- 14660694
TI  - Using quaternary structures to assess the evolutionary history of proteins: the
      case of the aspartate carbamoyltransferase.
AB  - Many evolutionary scenarios describing the history of proteins are based solely
      on phylogenetic studies. We have designed a new approach that allows
      ascertainment of such questionable scenarios by taking into account quaternary
      structures: we used aspartate carbamoyltransferase (ATCase) as a case study.
      Prokaryotic ATCases correspond to different classes of quaternary structures
      according to the mode of association of the catalytic PyrB subunit with other
      polypeptides, either the PyrI regulatory subunit (class B) or a dihydroorotase
      (class A), which may be active (PyrC, subclass A1) or inactive (PyrC', subclass
      A2). Class C is uniquely made up of trimers of PyrB. The PyrB phylogenetic tree
      is not congruent with the tree of life, but it became coherent when we recognized
      the existence of two families of ATCases, ATC I and ATC II. Remarkably, a very
      strong correlation was found between the pattern of PyrB phylogenetic clustering
      and the different classes of quaternary structures of ATCases. All class B
      ATCases form a clade in family ATC II, which also contains all eukaryotic
      sequences. In contrast, family ATC I is made up of classes A and C. These results
      suggest unexpected common ancestry for prokaryotic B and eukaryotic ATCases on
      the one hand, and for A and C on the other. Thus, the emergence of specific
      quaternary structures appears to have been a more recent event than the
      separation into the ATC I and ATC II families. We propose that different
      evolutionary constraints, depending on the identity of the partners interacting
      in the different kinds of holoenzymes, operated in a concerted way on the
      ancestral pyrB genes and the respective associated genes pyrI or pyrC, so as to
      maintain appropriate inter-polypeptides interactions at the level of quaternary
      structure. The process of coevolution of genes encoding proteins interacting in
      various holoenzymes has been assessed by calculating the correlation coefficient
      between their respective phylogenetic trees. Our approach integrating data
      obtained from the separate fields of structural biology and molecular evolution
      could be useful in other cases where pure statistical data need to receive
      independent confirmation.

PMID- 14660695
TI  - The evolution of SMC proteins: phylogenetic analysis and structural implications.
AB  - The SMC proteins are found in nearly all living organisms examined, where they
      play crucial roles in mitotic chromosome dynamics, regulation of gene expression,
      and DNA repair. We have explored the phylogenetic relationships of SMC proteins
      from prokaryotes and eukaryotes, as well as their relationship to similar ABC
      ATPases, using maximum-likelihood analyses. We have also investigated the
      coevolution of different domains of eukaryotic SMC proteins and attempted to
      account for the evolutionary patterns we have observed in terms of available
      structural data. Based on our analyses, we propose that each of the six
      eukaryotic SMC subfamilies originated through a series of ancient gene
      duplication events, with the condensins evolving more rapidly than the cohesins.
      In addition, we show that the SMC5 and SMC6 subfamily members have evolved
      comparatively rapidly and suggest that these proteins may perform redundant
      functions in higher eukaryotes. Finally, we propose a possible structure for the
      SMC5/SMC6 heterodimer based on patterns of coevolution.

PMID- 14660696
TI  - Heterogeneous selection on LEGCYC paralogs in relation to flower morphology and
      the phylogeny of Lupinus (Leguminosae).
AB  - An analysis of the molecular evolution of two LEGCYC paralogs in Lupinus
      (Genisteae: Leguminosae) reveals a varied history of site-specific and lineage
      specific evolutionary rates and selection both within and between loci. LEGCYC
      genes are homologous to regulatory loci known to control floral symmetry and
      adaxial flower organ identity in Antirrhinum and its relatives. Within Lupinus,
      L. densiflorus is unusual in having flowers with a proportionally smaller
      standard (upright adaxial petals) and larger wings (lateral petals) than other
      lupin species. Phylogenetic estimates of the nonsynonymous/synonymous
      substitution rate ratio, omega, suggest that along the L. densiflorus lineage,
      positive selection (omega > 1) acted at some codon sites of one paralog,
      LEGCYC1B, and greater purifying selection (omega < 1) acted at some sites of the
      other paralog, LEGCYC1A. Overall, LEGCYC1A appears to be evolving faster than
      LEGCYC1B, and both paralogs are evolving faster than the internal transcribed
      spacer (ITS) region of nr DNA. The predominant historical pattern inferred is a
      highly heterogeneous "selectional mosaic" which we suggest may be typical of the
      teosinte branched 1-cycloidea-PCF (TCP) class of transcriptional activators, and
      possibly other genes. Codon models that do not account for both site-specific and
      lineage-specific variation in omega do not detect positive selection at these
      loci. We suggest a modification of existing branch-site models involving an
      additional omega parameter along the foreground branch, to account for the
      effects of both greater positive selection and greater purifying selection at
      different codon sites along a particular branch. The higher rates of evolution
      and congruent phylogenetic signal of both LEGCYC paralogs show promise for the
      use of these genes as markers for phylogeny reconstruction at low taxonomic
      levels in Genisteae [corrected]

PMID- 14660697
TI  - Evolutionary convergence in adaptation of proteins to temperature: A4-lactate
      dehydrogenases of Pacific damselfishes (Chromis spp.).
AB  - We have compared the kinetic properties (Michaelis-Menten constant [K(m)] and
      catalytic rate constant [k(cat)]) and amino acid sequences of orthologs of
      lactate dehydrogenase-A (A(4)-LDH) from congeners of Pacific damselfishes (genus
      Chromis) native to cold-temperate and tropical habitats to elucidate mechanisms
      of enzymatic adaptation to temperature. Specifically, we determined whether the
      sites of adaptive variation and the types of amino acids involved in
      substitutions at these sites were similar in the Chromis orthologs and other
      orthologs of warm-adapted and cold-adapted A(4)-LDH previously studied. We report
      striking evolutionary convergence in temperature adaptation of this protein and
      present further support for the hypothesis that enzyme adaptation to temperature
      involves subtle amino acid changes at a few sites that affect the mobility of the
      portions of the enzyme that are involved in rate-determining catalytic
      conformational changes. We tested the predicted effects of differences in
      sequence using site-directed mutagenesis. A single amino acid substitution in a
      key hinge region of the A(4)-LDH molecule is sufficient to change the kinetic
      characteristics of a temperate A(4)-LDH to that of a tropical ortholog. This
      substitution is at the same location that was identified in previous studies of
      adaptive variation in A(4)-LDH and was hypothesized to be important in adjusting
      K(m) and k(cat). Our results suggest that certain sites within an enzyme, notably
      those that establish the energy changes associated with rate-limiting movements
      of protein structure during catalysis, are "hot spots" of adaptation and that
      common types of amino acid substitutions occur at these sites to adapt structural
      "flexibility" and kinetic properties. Thus, despite the wide array of options
      that proteins have to adjust their structural stabilities in the face of thermal
      stress, the adaptive changes that couple "flexibility" to alterations of function
      may be limited in their diversity.

PMID- 14660698
TI  - Effect of strong directional selection on weakly selected mutations at linked
      sites: implication for synonymous codon usage.
AB  - The fixation of weakly selected mutations can be greatly influenced by strong
      directional selection at linked loci. Here, I investigate a two-locus model in
      which weakly selected, reversible mutations occur at one locus and recurrent
      strong directional selection occurs at the other locus. This model is analogous
      to selection on codon usage at synonymous sites linked to nonsynonymous sites
      under strong directional selection. Two approximations obtained here describe the
      expected frequency of the weakly selected preferred alleles at equilibrium. These
      approximations, as well as simulation results, show that the level of codon bias
      declines with an increasing rate of substitution at the strongly selected locus,
      as expected from the well-understood theory that selection at one locus reduces
      the efficacy of selection at linked loci. These solutions are used to examine
      whether the negative correlation between codon bias and nonsynonymous
      substitution rates recently observed in Drosophila can be explained by this
      hitchhiking effect. It is shown that this observation can be reasonably well
      accounted for if a large fraction of the nonsynonymous substitutions on genes in
      the data set are driven by strong directional selection.

PMID- 14660699
TI  - Population genetics and geographic variation of alcohol dehydrogenase (Adh)
      paralogs and glucose-6-phosphate dehydrogenase (G6pd) in Drosophila mojavensis.
AB  - Populations of Drosophila mojavensis from the deserts of the Baja California
      peninsula and mainland Mexico utilize different cactus hosts with different
      alcohol contents. The enzyme alcohol dehydrogenase (ADH) has been proposed to
      play an important role in the adaptation of Drosophila species to their
      environment. This study investigates the role of ADH in the adaptation of the
      cactophilic D. mojavensis to its cactus host. In D. mojavensis and its sibling
      species, D. arizonae, the Adh gene has duplicated, giving rise to a
      larval/ovarian form (Adh-1) and an adult form (Adh-2). Studies of sequence
      variation presented here indicate that the Adh paralogs have followed different
      evolutionary trajectories. Adh-1 exhibits an excess of fixed amino acid
      replacements, suggesting adaptive evolution, which could have been a result of
      several host shifts that occurred during the divergence of D. mojavensis. A 17-bp
      intron haplotype polymorphism segregates in Adh-2 and has markedly different
      frequencies in the Baja and mainland populations. The presence of the intron
      polymorphism suggests possible selection for the maintenance of pre-mRNA
      structure. Finally, this study supports the proposed Baja California origination
      of D. mojavensis and subsequent colonization of the mainland accompanied by a
      host shift.

PMID- 14660700
TI  - Neighbor-net: an agglomerative method for the construction of phylogenetic
      networks.
AB  - We present Neighbor-Net, a distance based method for constructing phylogenetic
      networks that is based on the Neighbor-Joining (NJ) algorithm of Saitou and Nei.
      Neighbor-Net provides a snapshot of the data that can guide more detailed
      analysis. Unlike split decomposition, Neighbor-Net scales well and can quickly
      produce detailed and informative networks for several hundred taxa. We illustrate
      the method by reanalyzing three published data sets: a collection of 110 highly
      recombinant Salmonella multi-locus sequence typing sequences, the 135 "African
      Eve" human mitochondrial sequences published by Vigilant et al., and a collection
      of 12 Archeal chaperonin sequences demonstrating strong evidence for gene
      conversion. Neighbor-Net is available as part of the SplitsTree4 software
      package.

PMID- 14660701
TI  - Identification of a second egfr gene in Xiphophorus uncovers an expansion of the
      epidermal growth factor receptor family in fish.
AB  - The epidermal growth factor receptor (EGFR) gives name to a family of receptors
      formed by four members in mammals (EGFR, ErbB2, ErbB3, and ErbB4). Members of
      this family can be activated to become potent oncogenes, and many human and
      animal tumors express qualitatively or quantitatively altered receptors from this
      group. We have isolated and characterized a second egfr gene in the melanoma
      model fish Xiphophorus. Both Xiphophorus egfra and egfrb duplicates are co
      orthologs of the mammalian egfr gene. Database analysis showed that not only egfr
      but also erbB3 and erbB4 are present as duplicates in some fish species. They
      originated from ancient duplication events that might be consistent with the
      hypothesis of a fish-specific genome duplication. In Xiphophorus, the egfrb gene
      underwent a second duplication that generated the melanoma-inducing oncogene
      Xmrk. The study and comparison of some of the functional characteristics of both
      Xiphophorus EGF receptors, including expression profile, ligand-binding
      abilities, and intracellular signal transduction revealed that Xiphophorus Egfra
      not only shares common features with Egfrb and the human EGFR but also shows
      significant differences in its functional characteristics. The mechanism of
      maintenance of these duplicates remains to be clarified.

PMID- 14660702
TI  - Molecular phylogeny of euthyneura (mollusca: gastropoda).
AB  - A new phylogenetic hypothesis for Euthyneura is proposed based on the analysis of
      primary sequence data (mitochondrial cox1, trnV, rrnL, trnL(cun), trnA, trnP,
      nad6, and nad5 genes) and the phylogenetic utility of two rare genomic changes
      (the relative position of the mitochondrial trnP gene, and an insertion/deletion
      event in a conserved region of the mitochondrial Cox1 protein) is addressed. Both
      sources of phylogenetic information clearly rejected the monophyly of pulmonates,
      a group of gastropods well supported so far by morphological evidence. The marine
      basommatophoran pulmonate Siphonaria was placed within opisthobranchs and shared
      with them the insertion of a Glycine in the Cox 1 protein. The marine
      systellommatophoran pulmonate Onchidella was recovered at the base of the
      opisthobranch + Siphonaria clade. Opisthobranchs, Siphonaria, and Onchidella
      shared the relative position of the mitochondrial trnP gene between the
      mitochondrial trnA and nad6 genes. The land snails and slugs (stylommatophoran
      pulmonates) were recovered as an early split in the phylogeny of advanced
      gastropods. The monophyly of the Euthyneura (Opisthobranchia + Pulmonata) was
      rejected by the inclusion of the heterostrophan Pyramidella.

PMID- 14660703
TI  - Molecular evolution of bat color vision genes.
AB  - The two suborders of bats, Megachiroptera (megabats) and Microchiroptera
      (microbats), use different sensory modalities for perceiving their environment.
      Megabats are crepuscular and rely on a well-developed eyes and visual pathway,
      whereas microbats occupy a nocturnal niche and use acoustic orientation or
      echolocation more than vision as the major means of perceiving their environment.
      In view of the differences associated with their sensory systems, we decided to
      investigate the function and evolution of color vision (opsin genes) in these two
      suborders of bats. The middle/long wavelength (M/L) and short wavelength (S)
      opsin genes were sequenced from two frugivorous species of megabats,
      Haplonycteris fischeri and Pteropus dasymallus formosus, and one insectivorous
      species of microbat, Myotis velifer. Contrary to the situation in primates, where
      many nocturnal species have lost the functional S opsin gene, both crepuscular
      and strictly nocturnal species of bats that we examined have functional M/L and S
      opsin genes. Surprisingly, the S opsin in these bats may be sensitive to UV
      light, which is relatively more abundant at dawn and at dusk. The M/L opsin in
      these bats appears to be the L type, which is sensitive to red and may be helpful
      for identifying fruits among leaves or for other purposes. Most interestingly, H.
      fischeri has a recent duplication of the M/L opsin gene, representing to date the
      only known case of opsin gene duplication in non-primate mammals. Some of these
      observations are unexpected and may provide insights into the effect of nocturnal
      life on the evolution of opsin genes in mammals and the evolution of the life
      history traits of bats in general.

PMID- 14660704
TI  - Applicability of tandem affinity purification MudPIT to pathway proteomics in
      yeast.
AB  - A combined multidimensional chromatography-mass spectrometry approach known as
      "MudPIT" enables rapid identification of proteins that interact with a tagged
      bait while bypassing some of the problems associated with analysis of
      polypeptides excised from SDS-polyacrylamide gels. However, the reproducibility,
      success rate, and applicability of MudPIT to the rapid characterization of dozens
      of proteins have not been reported. We show here that MudPIT reproducibly
      identified bona fide partners for budding yeast Gcn5p. Additionally, we
      successfully applied MudPIT to rapidly screen through a collection of tagged
      polypeptides to identify new protein interactions. Twenty-five proteins involved
      in transcription and progression through mitosis were modified with a new tandem
      affinity purification (TAP) tag. TAP-MudPIT analysis of 22 yeast strains that
      expressed these tagged proteins uncovered known or likely interacting partners
      for 21 of the baits, a figure that compares favorably with traditional
      approaches. The proteins identified here comprised 102 previously known and 279
      potential physical interactions. Even for the intensively studied Swi2p/Snf2p,
      the catalytic subunit of the Swi/Snf chromatin remodeling complex, our analysis
      uncovered a new interacting protein, Rtt102p. Reciprocal tagging and TAP-MudPIT
      analysis of Rtt102p revealed subunits of both the Swi/Snf and RSC complexes,
      identifying Rtt102p as a common interactor with, and possible integral component
      of, these chromatin remodeling machines. Our experience indicates it is feasible
      for an investigator working with a single ion trap instrument in a conventional
      molecular/cellular biology laboratory to carry out proteomic characterization of
      a pathway, organelle, or process (i.e. "pathway proteomics") by systematic
      application of TAP-MudPIT.

PMID- 14660705
TI  - L-type Ca2+ channel and ryanodine receptor cross-talk in frog skeletal muscle.
AB  - The dihydropyridine receptors (DHPRs)/L-type Ca2+ channels of skeletal muscle are
      coupled with ryanodine receptors/Ca2+ release channels (RyRs/CRCs) located in the
      sarcoplasmic reticulum (SR). The DHPR is the voltage sensor for excitation
      contraction (EC) coupling and the charge movement component q gamma has been
      implicated as the signal linking DHPR voltage sensing to Ca2+ release from the
      coupled RyR. Recently, a new charge component, qh, has been described and related
      to L-type Ca2+ channel gating. Evidence has also been provided that the coupled
      RyR/CRC can modulate DHPR functions via a retrograde signal. Our aim was to
      investigate whether the newly described qh is also involved in the reciprocal
      interaction or cross-talk between DHPR/L-type Ca2+ channel and RyR/CRC. To this
      end we interfered with DHPR/L-type Ca2+ channel function using nifedipine and 1
      alkanols (heptanol and octanol), and with RyR/CRC function using ryanodine and
      ruthenium red (RR). Intramembrane charge movement (ICM) and L-type Ca2+ current
      (ICa) were measured in single cut fibres of the frog using the double-Vaseline
      gap technique. Our records showed that nifedipine reduced the amount of q gamma
      and qh moved by approximately 90% and approximately 55%, respectively, whereas 1
      alkanols completely abolished them. Ryanodine and RR shifted the transition
      voltages of q gamma and qh and of the maximal conductance of ICa by approximately
      4-9 mV towards positive potentials. All these interventions spared q beta. These
      results support the hypothesis that only q gamma; and qh arise from the movement
      of charged particles within the DHPR/L-type Ca2+ channel and that these charge
      components together with ICa are affected by a retrograde signal from RyR/CRC.

PMID- 14660707
TI  - Impact of mitochondrial inhibition on excitability and cytosolic Ca2+ levels in
      brainstem motoneurones from mouse.
AB  - Motoneurones (MNs) are particularly affected by the inhibition of mitochondrial
      metabolism, which has been linked to their selective vulnerability during
      pathophysiological states like hypoxia and amyotrophic lateral sclerosis (ALS), a
      fatal neurodegenerative disorder. To elucidate underlying events, we used sodium
      cyanide (CN) as a pharmacological inhibitor of complex IV of the mitochondrial
      respiratory chain ('chemical hypoxia') and investigated the cellular response in
      vulnerable and resistant neurone types. Bath application of 2 mm CN activated TTX
      insensitive Na+ conductances in vulnerable hypoglossal MNs, which depolarized
      these MNs by 10.2 +/- 1.1 mV and increased their action potential activity. This
      response was mimicked by sodium azide (2 mm) and largely prevented by
      preincubation with the antioxidants ascorbic acid (1 mm) and Trolox (750 microm),
      indicating an involvement of reactive oxygen species (ROS) in the activation
      mechanism. CN also elevated cytosolic [Ca2+] levels through (i) Ca2+ release from
      mitochondria-controlled stores, (ii) significant retardation of cytosolic Ca2+
      clearance rates, even when cytosolic ATP levels were held constant during whole
      cell recording, and (iii) secondary Ca2+ influx during elevated firing rates.
      Blocking mitochondrial ATP production additionally raised cytosolic Ca2+ levels
      and prolonged recovery of Ca2+ transients with a delay of 5-6 min. Comparative
      studies on hypoglossal MNs, facial MNs and dorsal vagal neurones suggested that
      CN responses were dominated by the activation of K+ conductances in resistant
      neurones, thus reducing excitability during mitochondrial inhibition. In summary,
      our observations therefore support a model where selective MN vulnerability
      results from a synergistic accumulation of risk factors, including low cytosolic
      Ca2+ buffering, strong mitochondrial impact on [Ca2+]i, and a mitochondria
      controlled increase in electrical excitability during metabolic disturbances.

PMID- 14660706
TI  - Liquid secretion properties of airway submucosal glands.
AB  - The tracheobronchial submucosal glands secrete liquid that is important for
      hydrating airway surfaces, supporting mucociliary transport, and serving as a
      fluid matrix for numerous secreted macromolecules including the gel-forming
      mucins. This review details the essential structural elements of airway glands
      and summarizes what is currently known regarding the ion transport processes
      responsible for producing the liquid component of gland secretion. Liquid
      secretion most likely arises from serous cells and is principally under neural
      control with muscarinic agonists, substance P, and vasoactive intestinal peptide
      (VIP) functioning as effective secretogogues. Liquid secretion is driven by the
      active transepithelial secretion of both Cl(-) and HCO(3)(-) and at least a
      portion of this process is mediated by the cystic fibrosis transmembrane
      conductance regulator (CFTR), which is highly expressed in glands. The potential
      role of submucosal glands in cystic fibrosis lung disease is discussed.

PMID- 14660708
TI  - Dynamic interactions of excitatory and inhibitory inputs in hypoglossal
      motoneurones: respiratory phasing and modulation by PKA.
AB  - The balance of excitation and inhibition converging upon a neurone is a principal
      determinant of neuronal output. We investigated the role of inhibition in shaping
      and gating inspiratory drive to hypoglossal (XII) motoneuronal activity. In
      neonatal rat medullary slices that generate a spontaneous respiratory rhythm,
      patch-clamp recordings were made from XII motoneurones, which were divided into
      three populations according to their inhibitory inputs: non-inhibited,
      inspiratory-inhibited and late-inspiratory-inhibited. In late-inspiratory
      inhibited motoneurones, blockade of GABA(A) receptors with bicuculline abolished
      inspiratory-phased inhibition and increased the duration of inspiratory drive
      currents. In inspiratory-inhibited motoneurones, bicuculline abolished phasic
      inhibition, which frequently revealed excitatory inspiratory drive currents. In
      non-inhibited motoneurones, neither bicuculline nor strychnine markedly changed
      inspiratory drive currents. Inhibitory currents in XII motoneurones were
      potentiated by protein kinase A (PKA) activity. Intracellular dialysis of the
      catalytic subunit of PKA or bath application of the PKA activator Sp-cAMP
      significantly increased the amplitude of expiratory-phased IPSCs without any
      change in IPSP frequency. Inspiratory-phased inhibition in inspiratory-inhibited
      motoneurones was potentiated by Sp-cAMP. We conclude that inspiratory-phased
      inhibition is prevalent in neonatal XII motoneurones and plays an important role
      in shaping motoneuronal output. These inhibitory inputs are modulated by PKA,
      which also modulates excitatory inputs.

PMID- 14660711
TI  - Relationship between vasodilatation and cerebral blood flow increase in impaired
      hemodynamics: a PET study with the acetazolamide test in cerebrovascular disease.
AB  - The changes in cerebral blood flow (CBF) and arterial-to-capillary blood volume
      (V(0)) induced by acetazolamide (ACZ) are expected to be parallel each other in
      the normal circulation; however, it has not been proven that the same changes in
      those parameters are observed in patients with cerebrovascular disease. To
      investigate the relationship between changes in CBF, vasodilatory capacity, and
      other hemodynamic parameters, the ACZ test was performed after an (15)O-gas PET
      study. METHODS: Twenty-two patients with unilateral major cerebral arterial
      occlusive disease underwent PET scans using the H(2)(15)O bolus method with the
      ACZ test after the (15)O-gas steady-state method. CBF and V(0) for each subject
      were calculated using the 3-weighted integral method as well as the nonlinear
      least-squares fitting method. After evaluation of accuracy in V(0) values, a new
      parameter, the CBF/V(0) ratio, which is expected to disclose arterial perfusion
      pressure, was also compared between the conditions. RESULTS: The regional CBF
      (rCBF) and V(0) increased significantly after ACZ administration in the
      hemisphere contralateral to the ischemic side. However, in a subgroup of patients
      who showed a significant reduction in the rCBF increase in the ipsilateral
      hemisphere (group A), the ACZ injection caused no change or a slight decrease in
      rCBF even though the V(0) showed a significant increase. Thus, the increases in
      rCBF and V(0) did not necessarily parallel each other in the ipsilateral
      hemispheres of patients who have impaired cerebral circulation. A parameter
      defined by the rCBF/V(0) ratio decreased significantly in the ipsilateral
      hemisphere of group A after ACZ administration, although the ratio showed no
      change in the contralateral hemisphere or in the other subgroup (group B).
      CONCLUSION: The change in the rCBF/V(0) ratio after ACZ challenge may represent
      an alteration in arterial perfusion pressure that is expected to indicate a
      critical hemodynamic status in patients with cerebrovascular disease, especially
      in patients who have a reduced rCBF response.

PMID- 14660709
TI  - Energy metabolism in heart failure.
AB  - Heart failure (HF) is a syndrome resulting from the inability of the cardiac pump
      to meet the energy requirements of the body. Despite intensive work, the
      pathogenesis of the cardiac intracellular abnormalities that result from HF
      remains incompletely understood. Factors that lead to abnormal contraction and
      relaxation in the failing heart include metabolic pathway abnormalities that
      result in decreased energy production, energy transfer and energy utilization.
      Heart failure also affects the periphery. Patients suffering from heart failure
      always complain of early muscular fatigue and exercise intolerance. This is
      linked in part to intrinsic alterations of skeletal muscle, among which decreases
      in the mitochondrial ATP production and in the transfer of energy through the
      phosphotransfer kinases play an important role. Alterations in energy metabolism
      that affect both cardiac and skeletal muscles argue for a generalized metabolic
      myopathy in heart failure. Recent evidence shows that decreased expression of
      mitochondrial transcription factors and mitochondrial proteins are involved in
      mechanisms causing the energy starvation in heart failure. This review will focus
      on energy metabolism alterations in long-term chronic heart failure with only a
      few references to compensated hypertrophy when necessary. It will briefly
      describe the energy metabolism of normal heart and skeletal muscles and their
      alterations in chronic heart failure. It is beyond the scope of this review to
      address the metabolic switches occurring in compensated hypertrophy; readers
      could refer to well-documented reviews on this subject.

PMID- 14660712
TI  - Postsurgical cerebral perfusion changes in idiopathic normal pressure
      hydrocephalus: a statistical parametric mapping study of SPECT images.
AB  - Our goal was to study cerebral blood flow (CBF) changes after surgery in a group
      of 15 patients with idiopathic normal pressure hydrocephalus (NPH). METHODS: We
      used hexamethylpropyleneamine oxime SPECT and statistical parametric mapping
      (SPM), an image analysis method that does not require prior selection of regions
      of interest. RESULTS: Our study showed areas of significant increase in perfusion
      in specific regions of both frontal lobes and the right parietal lobe. Regions of
      increased perfusion were found in the left prefrontal dorsolateral areas
      (Brodmann's areas 9 and 45 or 47), right frontal premotor area (Brodmann's area
      44), right medial prefrontal region (Brodmann's area 10 or 32), right frontal
      white matter area (superior longitudinalis fasciculus), and right basal ganglia
      (lenticular nucleus, putamen, and globus pallidus). In the right hemisphere,
      another region of increased perfusion was found in the inferior parietal lobule
      (Brodmann's area 40). The 2 areas most related to clinical improvement were
      Brodmann's area 32 and the frontal part of the left lobule of Reil insula.
      CONCLUSION: The results obtained with the SPM method of image analysis confirm
      and expand on previous CBF literature in NPH, with specific CBF regions located
      in frontal and parietal areas that improve after surgery in idiopathic NPH.

PMID- 14660713
TI  - N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an
      improved PET radioligand for serotonin transporters.
AB  - There has been considerable interest in the development of PET radioligands that
      are useful for imaging serotonin transporter (SERT) in the living human brain.
      For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for
      studying SERT in humans. However, this agent has some limitations. Recently, a
      new promising SERT PET radioligand, 3-(11)C-amino-4-(2
      dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently
      reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl
      2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have
      advantages over (11)C-labeled radioligands. The purpose of this study was to
      evaluate this newly developed (18)F-labeled PET radioligand as a promising agent
      for studying SERT in the living human brain. METHODS: This agent was evaluated by
      studying its in vitro binding to different monoamine transporters, its in vivo
      biodistributions in rats, its integrity and pharmacologic profiles in rat brain,
      and its distribution in a female baboon brain. RESULTS: In vitro binding assays
      showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant =
      0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the
      specific transporter) and showed more than 1,000- and 28,000-fold selectivity for
      SERT over norepinephrine transporter and dopamine transporter, respectively.
      Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow
      clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30,
      and 60 min after intravenous injection, respectively), with the specific binding
      peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in
      blood, muscle, lung, kidney, and liver was also initially high but cleared
      rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM,
      indicating that in vivo defluorination may occur. In vivo metabolism studies in
      rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of
      radioactivity was recovered as parent compound at 1 h after injection). However,
      it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered
      from plasma was the parent compound, with the majority of radioactivity in the
      plasma not extractable by ethyl acetate. Blocking studies showed significant
      decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus,
      hippocampus, and striatum) where SERT concentrations are high when rats were
      pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F
      ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were
      less significant when rats were pretreated with either methylphenidate or
      nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain
      peaked at approximately 1 h after injection and then declined slowly. The ratios
      of the radioactivity in the midbrain to that in the cerebellum (where the
      concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2,
      respectively. CONCLUSION: 4-(18)F-ADAM is suitable as a PET radioligand for
      studying SERT in the living brain. Further characterization of this new
      radioligand in humans is warranted.

PMID- 14660714
TI  - Correlation of 99mTc-DTPA SPECT of the blood-brain barrier with neurologic
      outcome after acute stroke.
AB  - We conducted a study on humans to determine whether quantitative evaluation of
      blood-brain barrier (BBB) breakdown using the (99m)Tc
      diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) SPECT technique at the peak
      time of stroke evolution can predict neurologic outcome. METHODS: Thirty
      consecutive patients with acute stroke of the middle cerebral artery occurring
      >24 h and <48 h before admission were included in the study. Each patient
      underwent a complete neurologic examination according to the Scandinavian stroke
      score at 72 h after the stroke (S1) and again at 30 d (S2). The difference
      between initial and late scores was calculated (Delta S) and used to evaluate the
      change in neurologic status. A CT scan was obtained on all patients to determine
      the volume of stroke. The integrity of the BBB was evaluated using (99m)Tc-DTPA
      brain SPECT. A quantitative index of BBB disruption was defined as the ratio of
      the mean counts/pixel in the infarcted region compared with the mean counts/pixel
      in the contralateral nonaffected hemisphere. SPECT perfusion imaging was also
      performed with (99m)Tc-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) at 24 h
      after the (99m)Tc-DTPA study. The relative perfusion in the infarct region was
      expressed as the percentage of contralateral perfusion. RESULTS: The mean (99m)Tc
      DTPA disruption index was 6.8 +/- 6.9 (range, 1-26.2). Seven patients (23%) had
      no BBB disruption. Statistical analysis showed that the disruption index was
      negatively correlated with Delta S (r = -0.423, P < 0.02). A disruption index of
      <2.5 was associated with a significantly better neurologic outcome (mean Delta S,
      17.5 +/- 9.5) compared with patients with an index of >2.5 (mean Delta S, -0.85
      +/- 4.97, P < 0.0001) with a sensitivity of 95% and a specificity of 89%. S2 was
      significantly correlated with S1 (r = 0.738, P < 0.001) and with Delta S (r =
      0.656, P < 0.001). Perfusion abnormalities on the (99m)Tc-HMPAO SPECT studies
      ranged between 12% and 90% (mean, 37.6% +/- 17.8%) compared with those on the
      contralateral nonaffected side. No correlation was found between (99m)Tc-HMPAO
      uptake and Delta S, infarct volume by CT, or disruption index. The CT volume
      measurements were negatively correlated with S2 (r = -0.560, P < 0.004) but not
      with Delta S. CONCLUSION: (99m)Tc-DTPA SPECT of the BBB combined with
      quantitative analysis in patients with acute stroke is significantly related to
      clinical outcome, with a distinct prognostic cutoff threshold of 2.5. The use of
      this radionuclide brain SPECT technique represents a unique application of
      conventional nondiffusible brain agents.

PMID- 14660715
TI  - Clinical usefulness of fusion of 131I SPECT and CT images in patients with
      differentiated thyroid carcinoma.
AB  - Precise localization of the foci of (131)I uptake for management of patients with
      differentiated thyroid carcinoma can be difficult because of a lack of anatomic
      landmarks. The objective of the present study was to demonstrate the clinical
      usefulness of (131)I SPECT/CT fusion images in patients with differentiated
      thyroid carcinoma. METHODS: CT and SPECT were performed 7 d after administration
      of a therapeutic dose of (131)I to 17 patients with differentiated thyroid
      carcinoma. External markers were placed at 3 locations on the skin of the patient
      to adjust the sections of CT and SPECT in the same geometric plane. Fusion images
      were constructed by combining the digital CT and SPECT images on a computer
      workstation. The data from both planar and SPECT (131)I images and CT images were
      first separately assessed by 2 nuclear medicine physicians. (131)I SPECT/CT
      fusion images were then interpreted. Fusion images were considered to improve
      image interpretation in comparison with CT and scintigraphy separately when they
      provided better localization of sites of increased radiopharmaceutical uptake.
      RESULTS: Both CT and (131)I SPECT showed the pathologic sites in 5 of 17 patients
      (29%). Fusion images were considered to be of benefit in 15 of 17 patients (88%).
      In 4 patients, CT showed normal-sized lymph nodes, whereas (131)I SPECT showed
      abnormal findings. In 3 patients with bone metastasis, fusion images confirmed
      the precision of the localization of abnormal (131)I uptake. Five bone metastases
      and 1 muscle metastasis were occult and were not seen on the CT images. Finally,
      (131)I scintigraphy findings were abnormal for 2 patients for whom the CT
      findings were initially considered normal. Fusion images confirmed the precision
      of the localization of physiologic (131)I uptake. CONCLUSION: For registration of
      anatomic and functional images in fusion imaging, the method using external
      markers was simple and practical. (131)I SPECT/CT fusion images using this
      technique may improve anatomically limited interpretation of (131)I scintigraphy
      alone in patients with differentiated thyroid carcinoma.

PMID- 14660716
TI  - Whole-body (18)F-FDG PET improves the management of patients with small cell lung
      cancer.
AB  - The aim of this study was to evaluate the impact of whole-body (18)F-FDG PET on
      staging and managing patients with small cell lung cancer (SCLC). METHODS: The
      treatment records of 42 consecutive patients (27 men, 15 women; mean age, 62 y;
      age range, 45-83 y) with SCLC were reviewed. Whole-body (18)F-FDG PET was
      performed for initial staging in 24 patients and for restaging after chemotherapy
      or radiation treatment in 20 patients. Two patients of the initial staging group
      were restaged with PET after therapy. PET findings were correlated with clinical
      and radiologic findings (CT of the chest and abdomen, bone scan, and CT or MRI of
      the brain). The impact of PET on staging and management decisions was determined.
      RESULTS: For 12 of 42 patients (29%), PET results changed the patient's
      management. In 8 patients (19%), PET resulted in a change of radiation therapy
      because of the detection of previously unknown tumor foci. Adjuvant radiation
      therapy was cancelled in 3 patients. A change of radiation field and volume was
      necessary in 5 patients. In 1 patient, PET results excluded extensive disease,
      which permitted surgical resection of the tumor. Chemotherapy was discontinued in
      2 patients and restarted in 1 patient on the basis of the PET findings. In 5
      patients (12%), PET excluded malignancy as the suspicious lesions found with
      conventional cross-sectional imaging did not take up (18)F-FDG. CONCLUSION: The
      results of this study show that (18)F-FDG PET has a major impact on the
      management of patients with SCLC, influencing both the stage and the management
      in 29% of patients. PET is a highly valuable tool for accurate target definition
      of radiation treatment by reducing the probability of overlooking involved areas.

PMID- 14660717
TI  - Application of a neural network to improve nodal staging accuracy with 18F-FDG
      PET in non-small cell lung cancer.
AB  - We proposed to train a back-propagation artificial neural network (aNN) on a
      cohort of surgically proven non-small cell lung cancers (NSCLCs) and compare its
      accuracy with that of a trained (18)F-FDG PET reader. We plan to show that an aNN
      trained on (18)F-FDG PET- and CT-derived data is more accurate in predicting the
      true surgicopathologic nodal stage than a human reader. METHODS: One hundred
      thirty-three NSCLC patients with surgically proven N status treated at the
      University of Washington Medical Center or the Veterans Affairs Puget Sound
      Health Care System between February 1998 and September 2002 were used as inputs
      for the creation of an aNN. From CT of the thorax and (18)F-FDG PET (neck to
      pelvis) performed before surgery, we extracted the primary tumor size and uptake
      (maximum pixel SUV [maxSUV]), normal lung and mediastinal uptake, and nodal
      uptake (maxSUV). Using the same 133 cases, the same output (surgical N status,
      N(0) to N(3)), and the same software configuration settings, scenarios were
      created to assess which input parameters were most influential in creating an
      optimal aNN. To compute this optimal aNN, cases were split randomly 100 times
      into a training subset of 103 cases and a testing subset of 30 cases having the
      same proportion of N(0), N(1), N(2), and N(3) cases. N status predicted by the
      aNN was compared with the proven surgical N status to calculate the aNN accuracy.
      The N status readings from (18)F-FDG PET were also compared with the surgical N
      status for the same cases to determine (18)F-FDG PET accuracy. RESULTS:
      Statistical tests demonstrate that the best aNN accuracy is achieved by using
      N(1)-N(2)- N(3) nodal maxSUV divided by background uptake, the primary tumor
      size, and primary tumor maxSUV as inputs. The aNN correctly predicted the N stage
      in 87.3% of the testing cases compared with 73.5% for the (18)F-FDG PET expert
      reader. Accuracy of the aNN increased to 94.8% (PET, 89.4%) when comparing N(0) +
      N(1) with N(2) or N(3) status and to 94.9% (PET, 91.9%) when comparing N(0) +
      N(1) with N(2) + N(3) status. CONCLUSION: A back-propagation aNN can be trained
      to predict hilar and mediastinal nodal involvement with greater accuracy than an
      expert (18)F-FDG PET reader. Such a tool could be used to improve clinical
      interpretations and for clinical training.

PMID- 14660718
TI  - 3'-18F-fluoro-3'-deoxy-L-thymidine: a new tracer for staging metastatic melanoma?
AB  - In this study, the feasibility of 3'-(18)F-fluoro-3'-deoxy-L-thymidine PET ((18)F
      FLT PET) for staging patients with clinical stage III melanoma was investigated.
      METHODS: Ten patients with melanoma and metastases to the locoregional draining
      lymph nodes, clinical stage III-based on physical examination, chest radiography,
      lactate dehydrogenase, and histopathologic confirmation-underwent a whole-body
      (18)F-FLT PET scan 1 h after injection of a median 400-MBq dose (range, 185-430
      MBq) of (18)F-FLT. All (18)F-FLT PET lesions were verified using the American
      Joint Committee on Cancer Staging System, which includes physical examination,
      spiral CT, ultrasound, chest radiography, and histopathologic examinations. Size
      and mitotic rate of metastatic lymph nodes and skin metastases were determined.
      RESULTS: All histopathologic samples and (18)F-FLT PET lesions were categorized
      over anatomic regions and correlated. All locoregional metastases were correctly
      visualized by (18)F-FLT PET. Region-based sensitivity for detection of lymph node
      metastatic disease was 88%. There were 3 true-negative and 2 false-positive
      lesions. The detection limit for lymph node metastases appeared to be
      approximately 6 mm or a mitotic rate of 9 mitoses per 2 mm(2). Two patients were
      upstaged by (18)F-FLT PET, which was confirmed by CT. In 3 patients, (18)F-FLT
      PET detected a total of 3 additional lesions with therapeutic consequences,
      without influencing staging. These lesions were initially missed by clinical
      staging. CONCLUSION: (18)F-FLT PET seems promising for (re)staging purposes in
      clinical stage III melanoma. Further research is needed, in which (18)F-FLT PET
      should be compared with (18)F-FDG PET.

PMID- 14660719
TI  - Shortened PET data acquisition protocol for the quantification of 18F-FDG
      kinetics.
AB  - A modified short dynamic protocol was defined and evaluated to predict kinetic
      parameters of (18)F-FDG metabolism from a dynamic data acquisition. METHODS: The
      evaluation included 151 datasets obtained from 60 patients examined with (18)F
      FDG and a dynamic data acquisition protocol of 60 min. Standardized uptake values
      (SUVs) were calculated for the individual time frames, and a 2-compartment model
      was applied to the data. The kinetic parameters and the (18)F-FDG influx,
      calculated from the model data, served as the reference for the analysis.
      Correlation was analyzed for the SUVs and the reference data. Subset analysis
      identified time intervals that can be used to predict the reference parameters
      based on a second-order polynomial function. RESULTS: Significant correlations
      were noted for SUVs and (18)F-FDG influx, vascular fraction (VB), and the rate
      constant k1. The influx was associated mainly with SUVs of late acquisition
      times, whereas higher correlations were noted for early acquisition intervals and
      VB, as well as k1. A short dynamic acquisition protocol was defined on the basis
      of a short dynamic sequence 1-10 min after tracer injection and a static
      acquisition 56-60 min after tracer application. The correlation coefficients
      exceeded 0.9 for influx, VB, and k1 when the SUVs of the input area (blood) and
      the target area were used to predict the kinetic parameters. CONCLUSION: A short
      dynamic data acquisition protocol can be used to obtain more detailed information
      about (18)F-FDG kinetics. The results demonstrate that (18)F-FDG influx, VB, and
      k1 can be estimated with high accuracy from SUVs.

PMID- 14660720
TI  - Correction for oral contrast artifacts in CT attenuation-corrected PET images
      obtained by combined PET/CT.
AB  - Recent studies have shown increased artifacts in CT attenuation-corrected (CTAC)
      PET images acquired with oral contrast agents because of misclassification of
      contrast as bone. We have developed an algorithm, segmented contrast correction
      (SCC), to properly transform CT numbers in the contrast regions from CT energies
      (40-140 keV) to PET energy at 511 keV. METHODS: A bilinear transformation,
      equivalent to that supplied by the PET/CT scanner manufacturer, for the
      conversion of linear attenuation coefficients of normal tissues from CT to PET
      energies was optimized for BaSO(4) contrast agent. This transformation was
      validated by comparison with the linear attenuation coefficients measured for
      BaSO(4) at concentrations ranging from 0% to 80% at 511 keV for PET transmission
      images acquired with (68)Ge rod sources. In the CT images, the contrast regions
      were contoured to exclude bony structures and then segmented on the basis of a
      minimum threshold CT number (300 Hounsfield units). The CT number in each pixel
      identified with contrast was transformed into the corresponding effective bone CT
      number to produce the correct attenuation coefficient when the data were
      translated by the manufacturer software into PET energy during the process of CT
      attenuation correction. CT images were then used for attenuation correction of
      PET emission data. The algorithm was validated with a phantom in which a lesion
      was simulated within a volume of BaSO(4) contrast and in the presence of a human
      vertebral bony structure. Regions of interest in the lesion, bone, and contrast
      on emission PET images reconstructed with and without the SCC algorithm were
      analyzed. The results were compared with those for images obtained with (68)Ge
      based transmission attenuation-corrected PET. RESULTS: The SCC algorithm was able
      to correct for contrast artifacts in CTAC PET images. In the phantom studies, the
      use of SCC resulted in an approximate 32% reduction in the apparent activity
      concentration in the lesion compared with data obtained from PET images without
      SCC and a <7.6% reduction compared with data obtained from (68)Ge-based
      attenuation-corrected PET images. In one clinical study, maximum standardized
      uptake value (SUV(max)) measurements for the lesion, bladder, and bowel were,
      respectively, 14.52, 13.63, and 13.34 g/mL in CTAC PET images, 59.45, 26.71, and
      37.22 g/mL in (68)Ge-based attenuation-corrected PET images, and 11.05, 6.66, and
      6.33 g/mL in CTAC PET images with SCC. CONCLUSION: Correction of oral contrast
      artifacts in PET images obtained by combined PET/CT yielded more accurate
      quantitation of the lesion and other, normal structures. The algorithm was tested
      in a clinical case, in which SUV(max) measurements showed discrepancies of 2%,
      1.3%, and 5% between (68)Ge-based attenuation-corrected PET images and CTAC PET
      images with SCC for the lesion, bladder, and bowel, respectively. These values
      correspond to 6.5%, 62%, and 66% differences between CTAC-based measurements and
      (68)Ge-based ones.

PMID- 14660721
TI  - Molecular targeting with radionuclides: state of the science.
AB  - Inherent in the application of advances in biomedical science to nuclear medicine
      is the concept of molecular targeting: the in vivo concentration of labeled
      tracer by a gene, its transcribed DNA, or its protein product. This mechanism of
      localization has been and is being exploited for both nuclear imaging and
      radioisotopic therapy. Agents, such as antisense molecules, aptamers, antibodies,
      and antibody fragments, can be aimed at molecular targets. Tumor and nerve cell
      receptors provide such targets. So do certain cellular physiologic activities,
      including metabolism, hypoxia, proliferation, apoptosis, angiogenesis, response
      to infection, and multiple drug resistance. In this article we review the
      principles of molecular targeting based on radioisotopic methods and provide
      examples from the literature. We discuss applications to imaging and therapy and
      point out the hurdles that must be overcome in bringing molecular targeting to
      clinical reality.

PMID- 14660722
TI  - 124I-labeled engineered anti-CEA minibodies and diabodies allow high-contrast,
      antigen-specific small-animal PET imaging of xenografts in athymic mice.
AB  - Prolonged clearance kinetics have hampered the development of intact antibodies
      as imaging agents, despite their ability to effectively deliver radionuclides to
      tumor targets in vivo. Genetically engineered antibody fragments display rapid,
      high-level tumor uptake coupled with rapid clearance from the circulation in the
      athymic mouse/LS174T xenograft model. The anticarcinoembryonic antigen (CEA)
      T84.66 minibody (single-chain Fv fragment [scFv]-C(H)3 dimer, 80 kDa) and T84.66
      diabody (noncovalent dimer of scFv, 55 kDa) exhibit pharmacokinetics favorable
      for radioimmunoimaging. The present work evaluated the minibody or diabody
      labeled with (124)I, for imaging tumor-bearing mice using a high-resolution small
      animal PET system. METHODS: Labeling was conducted with 0.2-0.3 mg of protein and
      65-98 MBq (1.7-2.6 mCi) of (124)I using an iodination reagent. Radiolabeling
      efficiencies ranged from 33% to 88%, and immunoreactivity was 42% (diabody) or
      >90% (minibody). In vivo distribution was evaluated in athymic mice bearing
      paired LS174T human colon carcinoma (CEA-positive) and C6 rat glioma (CEA
      negative) xenografts. Mice were injected via the tail vein with 1.9-3.1 MBq (53
      85 microCi) of (124)I-minibody or with 3.1 MBq (85 microCi) of (124)I-diabody and
      imaged at 4 and 18 h by PET. Some mice were also imaged using (18)F-FDG 2 d
      before imaging with (124)I-minibody. RESULTS: PET images using (124)I-labeled
      minibody or diabody showed specific localization to the CEA-positive xenografts
      and relatively low activity elsewhere in the mice, particularly by 18 h. Target
      to-background ratios for the LS174T tumors versus soft tissues using (124)I
      minibody were 3.05 at 4 h and 11.03 at 18 h. Similar values were obtained for the
      (124)I-diabody (3.95 at 4 h and 10.93 at 18 h). These results were confirmed by
      direct counting of tissues after the final imaging. Marked reduction of normal
      tissue activity, especially in the abdominal region, resulted in high-contrast
      images at 18 h for the (124)I-anti-CEA diabody. CEA-positive tumors as small as
      11 mg (<3 mm in diameter) could be imaged, and (124)I-anti-CEA minibodies,
      compared with (18)F-FDG, demonstrated highly specific localization. CONCLUSION:
      (124)I labeling of engineered antibody fragments provides a promising new class
      of tumor-specific probes for PET imaging of tumors and metastases.

PMID- 14660723
TI  - Genetically engineered antibody fragments and PET imaging: a new era of
      radioimmunodiagnosis.

PMID- 14660724
TI  - Synthesis of 18F-fluoroalkyl-beta-D-glucosides and their evaluation as tracers
      for sodium-dependent glucose transporters.
AB  - Three omega-(18)F-fluoro-n-alkyl-beta-D-glucosides (alkyl = ethyl (5a)), n-butyl
      (5b), and n-octyl (5c)) were synthesized and evaluated as potential substrates
      for the sodium/D-glucose cotransporter SGLT1. METHODS: The ligands were prepared
      by (18)F-fluoride displacement of the corresponding tetraacetyl-protected
      tosylate alkylglucoside precursors in CH(3)CN, followed by hydrolysis of the
      protective acetate esters with NaOMe/MeOH. Transport of the nonradioactive
      analogs 5a, 5b, and 5c by the human sodium-D-glucose cotransporter hSGLT1 was
      characterized in vitro in oocytes of Xenopus laevis that expressed hSGLT1. The
      biodistribution of the tracers was determined in mice and the presence of
      metabolites in the blood was investigated. Compound 5a was also evaluated in mice
      pretreated with phlorizin. The intrarenal distribution of 5a in mice kidney was
      visualized using autoradiography. RESULTS: The radiochemical yield of 5a, 5b, and
      5c was in the range of 8%-15% (end of bombardment) with a total synthesis time of
      90 min. The in vitro evaluation after expression of the hSGLT1 showed that 2'
      fluoroethyl-beta-D-glucoside (5a) was transported with similar Michaelis-Menten
      K(m) and V(max) (maximum velocity) values as compared with methyl-alpha-D
      glucopyranoside (alpha MDG). The more lipophilic compounds 5b and 5c were not
      transported but inhibited transport of alpha MDG. In vivo tissue distribution in
      mice revealed that 5a, 5b, and 5c were cleared mainly by the renal pathway and
      that 5a showed a significantly higher accumulation in the kidneys and a slower
      renal excretion as compared with 5b and 5c. Compound 5a was retained mainly in
      the renal outer medulla containing S3 segments of proximal tubules and the
      accumulation could be blocked by phlorizin pretreatment. Compound 5c passed the
      blood-brain barrier to some extent. CONCLUSION: The data indicate that 2'-(18)F
      fluoroethyl-beta-D-glucoside (5a) is a specific tracer of Na(+)-dependent glucose
      transport that may be used to visualize this transport activity in the S3
      segments of renal proximal tubules.

PMID- 14660725
TI  - Quantification of regional ventilation-perfusion ratios with PET.
AB  - The topographic matching of alveolar ventilation (V(A)) and perfusion (Q) is the
      main determinant of gas exchange efficiency of the lung. However, no pulmonary
      functional imaging technique has been shown to predict whole-lung gas exchange in
      health and disease. This study aims to present a PET-based method to estimate
      regional alveolar ventilation-to-perfusion ratios (V(A)/Q) predictive of arterial
      blood gases. METHODS: The method is based on the regional tracer kinetics of
      (13)N-nitrogen ((13)NN) after an intravenous bolus injection during a breath-hold
      period and subsequent washout from the lungs with resumption of breathing. The
      method takes into account the presence of inter- and intraregional
      nonuniformities at length scales smaller than the imaging spatial resolution. An
      algorithm used regional tracer washout to classify regional V(A)Q/ uniformity.
      Intraregional V(A)/Q mismatch in nonuniform regions was described with a 2
      compartment model. Regional V(A)/Q estimates were combined into a whole-lung
      distribution of V(A)/Q ratios and were used to compute global arterial blood
      gases. The method was applied to 3-dimensional PET data from anesthetized and
      mechanically ventilated sheep before and after methacholine bronchoconstriction
      (n = 3) and pulmonary embolism (n = 3) and after saline lung lavage (n = 3).
      RESULTS: PET images revealed regional changes in ventilation and perfusion
      consistent with the different disease models. Quantification of the images using
      PET-derived V(A)Q/ distributions showed unimodal and narrow distributions in
      control conditions that became wider and unimodal after pulmonary embolism and
      saline lung lavage and bimodal after bronchoconstriction. Images of regional gas
      exchange allowed for visualization of regional gas exchange. Arterial blood gases
      estimated from the PET-based V(A)/Q distributions closely agreed with measured
      values (partial pressure of oxygen, arterial [PaO(2)]: r(2) = 0.97, P < 0.001;
      partial pressure of carbon dioxide, arterial [PaCO(2)]: r(2) = 0.96, P < 0.001).
      CONCLUSION: Tracer kinetics analysis of PET images after an intravenous injection
      of (13)NN provides a quantitative assessment of regional V(A)/Q heterogeneity
      including that corresponding to length scales smaller than the spatial resolution
      of the imaging method. Quantification of V(A)/Q mismatch obtained with the
      presented technique is directly related to severity of gas exchange impairment as
      determined by arterial blood gases.

PMID- 14660726
TI  - 186Re-liposome labeling using 186Re-SNS/S complexes: in vitro stability, imaging,
      and biodistribution in rats.
AB  - Liposomes are important carriers for controlling the spatial and temporal
      distribution of drug molecules or other bioactive molecules. Radiolabeled
      liposomes have potential applications in diagnostic imaging and radionuclide
      therapy. The purpose of this study was to develop a practical method for labeling
      liposomes with therapeutic rhenium radionuclides, using (186)Re as an example.
      METHODS: An SNS pattern ligand, N,N-bis(2-mercaptoethyl)-N',N'
      diethylethylenediamine (BMEDA), and an S pattern ligand, benzene thiol (BT), were
      used to make 2 kinds of (186)Re-SNS/S complexes, (186)Re-BMEDA and (186)Re-BMEDA
      + BT. These (186)Re-SNS/S complexes were mixed with neutral liposomes
      encapsulating cysteine or (NH(4))(2)SO(4) to prepare (186)Re-liposomes. The in
      vitro labeling stability of (186)Re-liposomes was investigated by incubation in
      50% fetal bovine serum/50% phosphate-buffered saline, pH 7.4, at 37 degrees C.
      Rat distribution studies of (186)Re-liposomes after intravenous injection were
      also performed. RESULTS: The labeling efficiencies of (186)Re-liposomes were
      52.9%-81.3% depending on the (186)Re-SNS/S complex chosen and whether cysteine-
      or (NH(4))(2)SO(4)-encapsulated liposomes were used. (186)Re-(NH(4))(2)SO(4)
      liposomes labeled with (186)Re-BMEDA had the best in vitro labeling stability in
      serum with 89.8% +/- 3.1% of the radioactivity associated with liposomes at 24 h
      and 76.2% +/- 5.1% at 96 h. A specific activity of 1.85 GBq (50 mCi) of (186)Re
      per 50 mg of phospholipid could be achieved with good labeling stability.
      Biodistributions were followed for 72 h and showed good in vivo stability for
      (186)Re-liposomes that was characterized by a slow blood clearance and a
      gradually increasing spleen accumulation. (186)Re-BMEDA alone had fast blood
      clearance and no accumulation in spleen. CONCLUSION: A practical method for
      labeling liposomes with (186)Re using (186)Re-SNS/S complexes is described. The
      labeled (186)Re-liposomes were stable in serum and in vivo and could potentially
      be useful for radionuclide therapy.

PMID- 14660727
TI  - Radioimmunotherapy of non-Hodgkin's lymphoma with 90Y-DOTA humanized anti-CD22
      IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic
      response?
AB  - A DOTA (1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid)-conjugated,
      (111)In- and (90)Y-labeled humanized antibody to CD22, epratuzumab, was studied
      in patients with non-Hodgkin's lymphoma (NHL) to assess biodistribution and tumor
      targeting, pharmacokinetics, dosimetry, and anti-antibody response. Of particular
      interest was to evaluate whether pretherapy targeting and tumor dosimetry could
      predict therapeutic responses. METHODS: Patients received a pretherapy imaging
      study with (111)In-DOTA-epratuzumab IgG (0.75 mg/kg), followed about 1 wk later
      with (90)Y-DOTA-epratuzumab starting at a dose level of 0.185 GBq/m(2) (5
      mCi/m(2)) in patients who had prior high-dose chemotherapy (group 2), and at
      0.370 GBq/m(2) in patients who did not have a prior transplant (group 1), with
      escalation in 0.185-GBq/m(2) increments. RESULTS: The effective blood half-life
      for (111)In-DOTA epratuzumab was 36.1 +/- 7.9 h (n = 25) compared with 35.2 +/-
      7.0 h for (90)Y-DOTA-epratuzumab (n = 22). The whole-body half-life for (90)Y
      DOTA-epratuzumab estimated from (111)In-DOTA-epratuzumab scintigraphy was 58.3 +/
      4.7 h (n = 20), with urine collection confirming the loss of between 2.2% and
      15.9% of the injected activity over 3 d (n = 3). One-hundred sixteen of 165 CT
      confirmed lesions were visualized with (111)In-DOTA-epratuzumab. Radiation
      absorbed doses to liver, lungs, and kidneys averaged 0.55 +/- 0.13 (n = 17), 0.28
      +/- 0.06 (n = 17), and 0.38 +/- 0.07 mGy/MBq (n = 10), respectively, with 0.14 +/
      0.02 and 0.23 +/- 0.04 mGy/MBq delivered to the whole-body and red marrow,
      respectively. Tumor doses (n = 14 lesions in 10 patients) ranged from 1.0 to as
      much as 83 mGy/MBq for a 0.5-g lesion (median, 7.15 mGy/MBq). Group 2 patients
      were more likely to experience significant hematologic toxicities, but doses of
      up to 0.370 GBq/m(2) of (90)Y-DOTA-epratuzumab were tolerated with standard
      support measures, whereas patients in group 1 tolerated doses of up to 0.740
      GBq/m(2) with the potential for further escalation. Anti-tumor effects were seen
      in both indolent and aggressive NHL. The data also suggest that anti-tumor
      responses of potentially equal magnitude can occur irrespective of tumor
      targeting and tumor size. Hence, tumor response did not correlate with the
      radiation dose delivered or with the tumor being visualized by external imaging.
      An anti-antibody response to epratuzumab was detected by an enzyme-linked
      immunosorbent assay in only 2 of 16 patients. CONCLUSION: These results suggest
      that (90)Y-DOTA-epratuzmab is a promising agent for the treatment of NHL and
      warrants further study. There was evidence suggesting that in this system,
      factors other than tumor radiation dose and targeting may be involved in the
      success of radioimmunotherapy.

PMID- 14660728
TI  - When may a nonuniform distribution of 131I be considered uniform? An experimental
      basis for multicellular dosimetry.
AB  - To varying degrees, radiopharmaceuticals are distributed nonuniformly in tissue.
      At a macroscopic level, the radiopharmaceutical may appear to be uniformly
      distributed throughout the tissue. However, on closer inspection, not all cells
      in the tissue may be labeled with the radiopharmaceutical. Furthermore, the
      radioactivity in the cells may be localized only in certain compartments within
      the cell. This work uses a cell culture model to examine the impact of
      nonuniformity at the multicellular level on the lethal effects of (131)I.
      METHODS: A 3-dimensional tissue culture model was used to investigate the
      biologic effects of nonuniform distributions of (131)I in a large population of
      mammalian cells. Chinese hamster V79 cells were labeled with (131)I
      iododeoxyuridine ((131)IdU), mixed with unlabeled cells, and multicellular
      clusters (4 x 10(6) cells) were formed by gentle centrifugation. Thus, the
      labeled cells were randomly located in the cluster to achieve a uniform
      distribution of radioactivity at the macroscopic level, yet nonuniform at the
      multicellular level. The clusters were assembled as described and then maintained
      at 10.5 degrees C for 72 h to allow (131)I decays to accumulate. The clusters
      were then dismantled and the cells were plated for colony formation. RESULTS:
      When 100% of the cells were labeled, the surviving fraction of cells in the
      cluster was exponentially dependent on the cluster activity down to 0.1%
      survival. In contrast, when 10% of the cells were labeled, it was observed that
      the survival fraction begins to saturate at about 1% survival. Absorbed-dose
      estimates reveal that the mean lethal cluster dose is 4.5, 5.7, and 6.4 Gy for
      100%, 10%, and 1% labeling, respectively. CONCLUSION: These data indicate that
      when the distribution of (131)I is uniform at the macroscopic level, but
      nonuniform at the multicellular level, the mean absorbed dose to a tissue element
      may not be a suitable quantity for use in predicting biologic effect. Rather,
      cellular and multicellular dosimetry approaches may be necessary to predict the
      biologic effects of incorporated (131)I.

PMID- 14660729
TI  - Monitoring tumor cell proliferation by targeting DNA synthetic processes with
      thymidine and thymidine analogs.
AB  - The use of radiolabeled thymidine (TdR) and thymidine analogs as PET-based
      tracers of tumor growth rate is based on the assumption that measurement of
      uptake of these nucleosides, a function primarily of thymidine kinase-1 (TK(1))
      activity, provides an accurate measure of active cell proliferation in tumors.
      The goal of this study was to test this hypothesis and determine how well these
      tracers track changes in proliferation of tumor cells. METHODS: TK(1) activity; S
      phase fraction; and uptake of TdR, 3'-deoxy-3'-fluorothymidine (FLT), and 2'
      fluoro-5-methyl-1-(beta-D-2-arabino-furanosyl) uracil (FMAU) were determined in
      plateau-phase and exponentially growing cultures of 3 human and 3 murine tumor
      cell lines. RESULTS: TK(1) activity and S-phase fraction increased in all cell
      lines as cells moved from plateau-phase conditions to exponential growth. Some
      cell lines had relatively large TK(1) activities and S-phase fractions under
      plateau-phase conditions, consistent with a loss of normal cell cycle checkpoint
      control in these cells. There were also 2 cell lines in which TK(1) activity
      changed little as cells moved from the plateau phase to exponential growth,
      suggesting that in these cell lines, de novo nucleotide synthesis pathways
      predominate over salvage pathways. Both TdR and FLT detected changes in TK(1)
      activity. The slope of the relationship between TdR uptake and TK(1) activity was
      nearly twice that for FLT and more than 40-fold that for FMAU. CONCLUSION:
      Although not all tumors show a strong TK(1) dependence of proliferation, in all
      cell lines for which proliferation is highly TK(1) dependent, phosphorylation of
      TdR or FLT accurately reflects changes in TK(1) enzyme activity.

PMID- 14660730
TI  - Lipiodol solution of 188Re-HDD as a new therapeutic agent for transhepatic
      arterial embolization in liver cancer: preclinical study in a rabbit liver cancer
      model.
AB  - It has been reported that lipiodol solution of (188)Re-labeled 2,2,9,9
      tetramethyl-4,7-diaza-1,10-decanedithiol (TDD), an N(2)S(2) derivative, shows
      excellent targeting of liver cancer after transhepatic arterial embolization
      (TAE). However, its tumor retention is not high enough to treat liver cancer.
      Therefore, a new form of TDD, 4-hexadecyl-TDD (HDD), was developed to improve
      tumor retention by introducing a long alkyl chain. In this study, we compared the
      tumor retention properties of (188)Re-HDD/lipiodol and (188)Re-TDD/lipiodol,
      using a rabbit liver cancer model, and performed dosimetry using the results.
      METHODS: The VX2 cancer cell line was implanted into the livers of 7 rabbits. TAE
      was performed on 3 rabbits with (188)Re-TDD/lipiodol and on 4 rabbits with
      (188)Re-HDD/lipiodol, and conjugated anterior and posterior planar scans were
      obtained at 1, 2, 6, 24, and 48 h after TAE. From these images, tumor retention
      was calculated and compared between (188)Re-TDD and (188)Re-HDD. Afterward, the
      required dose of radioactivity and the radiation dosimetry for exposure of major
      organs were calculated using MIRDOSE3.1 software. RESULTS: The residence times of
      radioactivity in the liver were 10.2 +/- 1.0 h in the (188)Re-TDD group and 17.6
      +/- 0.8 h in the (188)Re-HDD group (P = 0.034). The required radioactivity for
      100 Gy of irradiation to 2.64- to 5.27-cm tumors was 142-1,070 MBq of (188)Re-HDD
      in the rabbit model. The radiation exposures for the major organs were within the
      tolerable range, and the S-value for the whole body (effective dose equivalent)
      was calculated to be 0.209 mSv/MBq. CONCLUSION: Introduction of a long alkyl
      chain significantly improved the tumor retention of (188)Re-HDD/lipiodol,
      compared with that of (188)Re-TDD/lipiodol. Moreover, the required radioactivity
      for humans and the radiation exposure were within the feasible range for clinical
      application.

PMID- 14660731
TI  - 131I dosimetry and thyroid stunning.

PMID- 14660732
TI  - The move to preserve therapeutic cloning.

PMID- 14660735
TI  - Quorum sensing in Staphylococcus infections.
AB  - Quorum sensing via the accessory gene regulator (agr) system has been assigned a
      central role in the pathogenesis of staphylococci, particularly Staphylococcus
      aureus. While the control of virulence gene expression in vitro by agr has been
      relatively straightforward to describe, regulation of both the quorum response
      itself and virulence genes in vivo is considerably more complex. The quorum
      response is highly dependent upon the environment in which the organism is grown
      and is strongly influenced by additional regulators that respond to signals other
      than cell density. There is increasing evidence that the agr phenotype may
      influence the behavior and pathogenesis of biofilm-associated S. aureus and S.
      epidermidis and may contribute to the chronic nature of some biofilm-associated
      infections.

PMID- 14660734
TI  - Mechanisms for pituitary tumorigenesis: the plastic pituitary.
AB  - The anterior pituitary gland integrates the repertoire of hormonal signals
      controlling thyroid, adrenal, reproductive, and growth functions. The gland
      responds to complex central and peripheral signals by trophic hormone secretion
      and by undergoing reversible plastic changes in cell growth leading to
      hyperplasia, involution, or benign adenomas arising from functional pituitary
      cells. Discussed herein are the mechanisms underlying hereditary pituitary
      hypoplasia, reversible pituitary hyperplasia, excess hormone production, and
      tumor initiation and promotion associated with normal and abnormal pituitary
      differentiation in health and disease.

PMID- 14660737
TI  - Do allelic variants of SLC6A14 predispose to obesity?
AB  - Obesity is arguably the world's most prevalent nutritional disorder and is a
      substantial contributor to morbidity and early mortality. Obesity is known to
      have a strong genetic component, but the specific influential genes in humans are
      largely unknown. A new paper describes a genetic variant that appears as though
      it may cause some people to be fatter or thinner than others (see the related
      article beginning on page 1762). This commentary considers the strength of the
      evidence in support of this finding and discusses additional research questions
      that should be addressed in further evaluations of this genetic variant as a
      putative contributor to human obesity.

PMID- 14660736
TI  - Quorum sensing and biofilm formation in Streptococcal infections.
AB  - Members of the bacterial genus Streptococcus are responsible for causing a wide
      variety of infections in humans. Many Streptococci use quorum-sensing systems to
      regulate several physiological properties, including the ability to incorporate
      foreign DNA, tolerate acid, form biofilms, and become virulent. These quorum
      sensing systems are primarily made of small soluble signal peptides that are
      detected by neighboring cells via a histidine kinase/response regulator pair.

PMID- 14660738
TI  - Genes required for B cell development.
AB  - Mutations in a variety of genes can cause congenital agammaglobulinemia and a
      failure of B cell development. The currently known genes encode components of the
      pre-B cell receptor or proteins that are activated by cross-linking of the pre-B
      cell receptor. Defects in these genes result in a block in B cell differentiation
      at the pro-B to pre-B cell transition. A patient with a translocation involving a
      previously unknown gene, LRRC8, demonstrated a block at exactly the same point in
      B cell differentiation (see the related article beginning on page 1707). It will
      be interesting to determine whether the protein encoded by this gene interacts
      with the pre-B cell receptor signal transduction pathway or is involved in a new
      pathway.

PMID- 14660739
TI  - Complement system on the attack in autoimmunity.
AB  - The antiphospholipid syndrome is characterized clinically by fetal loss and
      thrombosis and serologically by the presence of autoantibodies to lipid-binding
      proteins. In a model of this procoagulant condition in which these antibodies are
      injected into pregnant mice, fetal loss was prevented by blocking of complement
      activation. Specifically, interaction of complement component 5a (C5a) with its
      receptor is necessary for thrombosis of placental vasculature. Inhibition of
      complement activation may have a therapeutic role in this disease.

PMID- 14660740
TI  - Dominant-negative diabetes insipidus and other endocrinopathies.
AB  - Familial neurohypophyseal diabetes insipidus (FNDI) in humans is an autosomal
      dominant disorder caused by a variety of mutations in the arginine vasopressin
      (AVP) precursor. A new report demonstrates how heterozygosity for an AVP mutation
      causes FNDI (see the related article beginning on page 1697). Using an AVP knock
      in mutation in mice, the study shows that FNDI is caused by retention of AVP
      precursors and progressive loss of AVP-producing neurons.

PMID- 14660741
TI  - Complement C5a receptors and neutrophils mediate fetal injury in the
      antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and
      thrombosis in the presence of antiphospholipid (aPL) Ab's. Currently, therapy for
      pregnant women with APS is focused on preventing thrombosis, but anticoagulation
      is only partially successful in averting miscarriage. We hypothesized that
      complement activation is a central mechanism of pregnancy loss in APS and tested
      this in a model in which pregnant mice receive human IgG containing aPL Ab's.
      Here we identify complement component C5 (and particularly its cleavage product
      C5a) and neutrophils as key mediators of fetal injury, and we show that Ab's or
      peptides that block C5a-C5a receptor interactions prevent pregnancy
      complications. The fact that F(ab)'2 fragments of aPL Ab's do not mediate fetal
      injury and that C4-deficient mice are protected from fetal injury suggests that
      activation of the complement cascade is initiated via the classical pathway.
      Studies in factor B-deficient mice, however, indicate that alternative pathway
      activation is required and amplifies complement activation. In contrast,
      activating Fc gamma Rs do not play an important role in mediating aPL Ab-induced
      fetal injury. Our findings identify the key innate immune effectors engaged by
      pathogenic autoantibodies that mediate poor pregnancy outcomes in APS and provide
      novel and important targets for prevention of pregnancy loss in APS.

PMID- 14660742
TI  - Proinflammatory functions of vascular endothelial growth factor in alloimmunity.
AB  - Vascular endothelial growth factor (VEGF), an established angiogenesis factor, is
      expressed in allografts undergoing rejection, but its function in the rejection
      process has not been defined. Here, we initially determined that VEGF is
      functional in the trafficking of human T cells into skin allografts in vivo in
      the humanized SCID mouse. In vitro, we found that VEGF enhanced endothelial cell
      expression of the chemokines monocyte chemoattractant protein 1 and IL-8, and in
      combination with IFN-gamma synergistically induced endothelial cell production of
      the potent T cell chemoattractant IFN-inducible protein-10 (IP-10). Treatment of
      BALB/c (H-2d) recipients of fully MHC-mismatched C57BL/6 (H-2b) donor hearts with
      anti-VEGF markedly inhibited T cell infiltration of allografts and acute
      rejection. Anti-VEGF failed to inhibit T cell activation responses in vivo, but
      inhibited intragraft expression of several endothelial cell adhesion molecules
      and chemokines, including IP-10. In addition, whereas VEGF expression was
      increased, neovascularization was not associated with acute rejection, and
      treatment of allograft recipients with the angiogenesis inhibitor endostatin
      failed to inhibit leukocyte infiltration of the grafts. Thus, VEGF appears to be
      functional in acute allograft rejection via its effects on leukocyte trafficking.
      Together, these observations provide mechanistic insight into the proinflammatory
      function of VEGF in immunity.

PMID- 14660744
TI  - Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution
      and control graft-versus-host disease while maintaining graft-versus-leukemia.
AB  - CD4+CD25+ regulatory T cells (Treg's) play a pivotal role in preventing organ
      specific autoimmune diseases and in inducing tolerance to allogeneic organ
      transplants. We and others recently demonstrated that high numbers of Treg's can
      also modulate graft-versus-host disease (GVHD) if administered in conjunction
      with allogeneic hematopoietic stem cell transplantation in mice. In a clinical
      setting, it would be impossible to obtain enough freshly purified Treg's from a
      single donor to have a therapeutic effect. Thus, we performed regulatory T cell
      expansion ex vivo by stimulation with allogeneic APCs, which has the additional
      effect of producing alloantigen-specific regulatory T cells. Here we show that
      regulatory T cells specific for recipient-type alloantigens control GVHD while
      favoring immune reconstitution. Irrelevant regulatory T cells only mediate a
      partial protection from GVHD. Preferential survival of specific regulatory T
      cells, but not of irrelevant regulatory T cells, was observed in grafted animals.
      Additionally, the use of specific regulatory T cells was compatible with some
      form of graft-versus-tumor activity. These data suggest that recipient-type
      specific Treg's could be preferentially used in the control of GVHD in future
      clinical trials.

PMID- 14660743
TI  - Mast cells are required for experimental oral allergen-induced diarrhea.
AB  - Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory
      diseases that are occurring with increasing incidence and severity. An essential
      question concerning these disorders is to determine the specific cells and
      mediators responsible for specific clinical manifestations. With this in mind, we
      developed a murine model of oral allergen-induced intestinal inflammation
      accompanied by strong Th2-associated humoral and cellular responses and focused
      on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized
      mice to repeated doses of intragastric OVA induced genetically restricted, dose
      dependent, acute diarrhea associated with increased intestinal permeability,
      eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of
      anaphylaxis, even though they developed marked intestinal mucosal mast cell
      degranulation. Notably, experiments involving mast cell depletion (with anti-c
      kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a
      critical effector role for mast cells in mediating allergic diarrhea.
      Furthermore, allergic diarrhea was dependent upon synergistic signaling induced
      by serotonin and platelet-activating factor (PAF), but not histamine. These
      results demonstrate that oral allergen-induced diarrhea associated with
      experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin,
      and PAF dependent.

PMID- 14660745
TI  - A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals
      progressive loss of vasopressin-producing neurons.
AB  - Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant
      disorder caused by mutations in the arginine vasopressin (AVP) precursor. The
      pathogenesis of FNDI is proposed to involve mutant protein-induced loss of AVP
      producing neurons. We established murine knock-in models of two different
      naturally occurring human mutations that cause FNDI. A mutation in the AVP signal
      sequence [A(-1)T] is associated with a relatively mild phenotype or delayed
      presentation in humans. This mutation caused no apparent phenotype in mice. In
      contrast, heterozygous mice expressing a mutation that truncates the AVP
      precursor (C67X) exhibited polyuria and polydipsia by 2 months of age and these
      features of DI progressively worsened with age. Studies of the paraventricular
      and supraoptic nuclei revealed induction of the chaperone protein BiP and
      progressive loss of AVP-producing neurons relative to oxytocin-producing neurons.
      In addition, Avp gene products were not detected in the neuronal projections,
      suggesting retention of WT and mutant AVP precursors within the cell bodies. In
      summary, this murine model of FNDI recapitulates many features of the human
      disorder and demonstrates that expression of the mutant AVP precursor leads to
      progressive neuronal cell loss.

PMID- 14660746
TI  - A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in
      humans.
AB  - A girl with congenital agammaglobulinemia and minor facial anomalies lacked B
      cells in peripheral blood: karyotypic analysis of white blood cells showed
      balanced translocation, t(9;20)(q33.2;q12). In the current study, we isolated a
      novel gene, leucine-rich repeat-containing 8 (LRRC8), at the translocation site
      on chromosome 9. It has four transmembrane helices with one isolated and eight
      sequentially located leucine-rich repeats (LRRs) and constitutes a new protein
      family. It is expressed on T cells as well as on B-lineage cells. Translocation
      truncates the LRRC8 gene, resulting in deletion of the eighth, ninth, and half of
      the seventh LRR domains located close to the C-terminal. The truncated form of
      the LRRC8 gene is transcribed with sequences from the noncoding region adjacent
      to the truncated seventh LRR. Protein products derived from the truncated gene
      are coexpressed on white blood cells with the intact LRRC8 protein from the
      untranslocated allele. Transplantation experiments with murine bone marrow cells
      that were forced to express the truncated LRRC8 show that expression of the
      truncated protein inhibited B cell development. These results indicate that LRRC8
      is responsible for the B cell deficiency in this patient and is required for B
      cell development.

PMID- 14660747
TI  - Intravital microscopy identifies selectins that regulate T cell traffic into
      allografts.
AB  - T cell homing to sites of injury and inflammation is a critical step for adaptive
      immune responses. While much has been learned regarding T cell homing to lymphoid
      tissues, few studies have directly observed trafficking events during an effector
      response. In this study, we developed a model that uses intravital fluorescence
      videomicroscopy to determine the molecules critical to T cell rolling within skin
      allograft microvasculature during the effector phase of the rejection response.
      Additional studies were performed to quantify T cell infiltrates as rejection
      progressed. We found that P-selectin and E-selectin expressed on postcapillary
      venules play overlapping roles in the recruitment of activated T cells in a SCID
      reconstitution model of skin graft rejection and are important in T cell
      accumulation at the graft site. Surprisingly, we also found that naive T cells
      are recruited and accumulate via constitutive T cell L-selectin and upregulated L
      selectin ligands on rejecting allograft vasculature. These data indicated that a
      specific retinue of molecules is upregulated during the rejection response, and
      they suggest potential future therapeutic targets.

PMID- 14660748
TI  - Myc confers androgen-independent prostate cancer cell growth.
AB  - Prostate cancer is one of the most diagnosed and mortal cancers in western
      countries. A major clinical problem is the development of androgen-independent
      prostate cancer (AIPC) during antihormonal treatment. The molecular mechanisms
      underlying the change from androgen dependence to independence of these tumors
      are poorly understood and represent a challenge to develop new therapies. Based
      on genetic data showing amplification of the c-myc gene in AIPC, we studied the
      ability of c-myc to confer AIPC cell growth. Human androgen-dependent prostate
      cancer cells overexpressing c-myc grew independently of androgens and presented
      tumorigenic properties in androgen-depleted conditions. Analysis of signalling
      pathways by pharmacological inhibitors of the androgen receptor (AR) or by RNA
      interference directed against AR or c-myc showed that c-myc acted downstream of
      AR through multiple growth effectors. Thus c-myc is required for androgen
      dependent growth and following ectopic expression can induce androgen-independent
      growth. Moreover, RNA interference directed against c-myc showed that growth of
      human AIPC cells, AR-positive or -negative, required c-myc expression.
      Furthermore, we showed that c-myc-overexpressing cells retain a functional p53
      pathway and thus respond to etoposide.

PMID- 14660749
TI  - The molecular basis for adhesion-mediated suppression of reactive oxygen species
      generation by human neutrophils.
AB  - Human neutrophil adherence to ECMs induces an initial inhibition of stimulated
      reactive oxygen species (ROS) formation, followed by an enhanced phase of oxidant
      production. The initial integrin-mediated suppression of ROS constitutes a
      mechanism to prevent inappropriate tissue damage as leukocytes migrate to
      inflammatory sites. The Rac2 guanosine 5'-triphosphatase (GTPase) is a critical
      regulatory component of the phagocyte NADPH oxidase. We show that activation of
      Rac2 is inhibited in adherent neutrophils, correlating with inhibition of ROS
      formation. Conversely, NADPH oxidase components p47 and p67 assemble normally,
      suggesting a specific action of adhesion on the Rac2 molecular switch.
      Reconstitution with activated Rac2 restored rapid NADPH oxidase activation
      kinetics to adherent neutrophils, establishing that inhibition was due to
      defective Rac2 activity. We provide evidence that integrins inhibit Rac2
      activation via a membrane-associated guanine nucleotide exchange factor, likely
      to be Vav1. Activation of Vav1, but not its upstream activator, Syk, is
      suppressed by cell adhesion. Vav1 activity is inhibited due to dephosphorylation
      of the regulatory Tyr174 via enhanced tyrosine phosphatase activity in adherent
      cells. These studies identify an integrin-mediated pathway in which Vav1 is as a
      strong candidate for the critical regulatory point in suppression of Rac2
      activation and ROS generation during inflammatory responses.

PMID- 14660750
TI  - Notch ligation by Delta1 inhibits peripheral immune responses to transplantation
      antigens by a CD8+ cell-dependent mechanism.
AB  - Notch signaling plays a fundamental role in determining the outcome of
      differentiation processes in many tissues. Notch signaling has been implicated in
      T versus B cell lineage commitment, thymic differentiation, and bone marrow
      hematopoietic precursor renewal and differentiation. Notch receptors and their
      ligands are also expressed on the surface of mature lymphocytes and APCs, but the
      effects of Notch signaling in the peripheral immune system remain poorly defined.
      The aim of the studies reported here was to investigate the effects of signaling
      through the Notch receptor using a ligand of the Delta-like family. We show that
      Notch ligation in the mature immune system markedly decreases responses to
      transplantation antigens. Constitutive expression of Delta-like 1 on alloantigen
      bearing cells renders them nonimmunogenic and able to induce specific
      unresponsiveness to a challenge with the same alloantigen, even in the form of a
      cardiac allograft. These effects could be reversed by depletion of CD8+ cells at
      the time of transplantation. Ligation of Notch on splenic CD8+ cells results in a
      dramatic decrease in IFN-gamma with a concomitant enhancement of IL-10
      production, suggesting that Notch signaling can alter the differentiation
      potential of CD8+ cells. These data implicate Notch signaling in regulation of
      peripheral immunity and suggest a novel approach for manipulating deleterious
      immune responses.

PMID- 14660751
TI  - Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell
      maintenance and DNA repair.
AB  - Acute myelogenous leukemias (AMLs) are genetically heterogeneous and
      characterized by chromosomal rearrangements that produce fusion proteins with
      aberrant transcriptional regulatory activities. Expression of AML fusion proteins
      in transgenic mice increases the risk of myeloid leukemias, suggesting that they
      induce a preleukemic state. The underlying molecular and biological mechanisms
      are, however, unknown. To address this issue, we performed a systematic analysis
      of fusion protein transcriptional targets. We expressed AML1/ETO, PML/RAR, and
      PLZF/RAR in U937 hemopoietic precursor cells and measured global gene expression
      using oligonucleotide chips. We identified 1,555 genes regulated concordantly by
      at least two fusion proteins that were further validated in patient samples and
      finally classified according to available functional information. Strikingly, we
      found that AML fusion proteins induce genes involved in the maintenance of the
      stem cell phenotype and repress DNA repair genes, mainly of the base excision
      repair pathway. Functional studies confirmed that ectopic expression of fusion
      proteins constitutively activates pathways leading to increased stem cell renewal
      (e.g., the Jagged1/Notch pathway) and provokes accumulation of DNA damage. We
      propose that expansion of the stem cell compartment and induction of a mutator
      phenotype are relevant features underlying the leukemic potential of AML
      associated fusion proteins.

PMID- 14660752
TI  - The SLC6A14 gene shows evidence of association with obesity.
AB  - In our previous genome-wide scan of Finnish nuclear families, obesity was linked
      to chromosome Xq24. Here we analyzed this 15-Mb region by genotyping 9
      microsatellite markers and 36 single nucleotide polymorphisms (SNPs) for 11
      positional and functional candidate genes in an extended sample of 218 obese
      Finnish sibling pairs (sibpairs) (BMI > 30 kg/m2). Evidence of linkage emerged
      mainly from the obese male sibpairs, suggesting a gender-specific effect for the
      underlying gene. By constructing haplotypes among the obese male sibpairs, we
      restricted the region from 15 Mb to 4 Mb, between markers DXS8088 and DXS8067.
      Regional functional candidate genes were tested for association in an initial
      sample of 117 cases and 182 controls. Significant evidence was observed for
      association for an SNP in the 3'-untranslated region of the solute carrier family
      6 member 14 (SLC6A14) gene (P = 0.0002) and for SNP haplotypes of the SLC6A14
      gene (P = 0.0007-0.006). Furthermore, an independent replication study sample of
      837 cases and 968 controls from Finland and Sweden also showed significant
      differences in allele frequencies between obese and non-obese individuals (P =
      0.003). The SLC6A14 gene is an interesting novel candidate for obesity because it
      encodes an amino acid transporter, which potentially regulates tryptophan
      availability for serotonin synthesis and thus possibly affects appetite control.

PMID- 14660753
TI  - Harm reduction.

PMID- 14660754
TI  - Beware the rooster: smokeless tobacco companies who claim they want to help.
AB  - It should not be assumed that smokeless tobacco manufacturers share our public
      health goals

PMID- 14660755
TI  - Germany: still sleeping with the enemy.

PMID- 14660757
TI  - Australia: reviewing the act, industry-style.

PMID- 14660758
TI  - Latvia: window of opportunity.

PMID- 14660759
TI  - Finland: floating loopholes.

PMID- 14660760
TI  - Papua New Guinea: BAT's "utter rubbish".

PMID- 14660761
TI  - Sri Lanka: business as usual.

PMID- 14660762
TI  - World: how Formula One swerved round health.

PMID- 14660766
TI  - Effect of smokeless tobacco (snus) on smoking and public health in Sweden.
AB  - OBJECTIVE: To review the evidence on the effects of moist smokeless tobacco
      (snus) on smoking and ill health in Sweden. METHOD: Narrative review of published
      papers and other data sources (for example, conference abstracts and internet
      based information) on snus use, use of other tobacco products, and changes in
      health status in Sweden. RESULTS: Snus is manufactured and stored in a manner
      that causes it to deliver lower concentrations of some harmful chemicals than
      other tobacco products, although it can deliver high doses of nicotine. It is
      dependence forming, but does not appear to cause cancer or respiratory diseases.
      It may cause a slight increase in cardiovascular risks and is likely to be
      harmful to the unborn fetus, although these risks are lower than those caused by
      smoking. There has been a larger drop in male daily smoking (from 40% in 1976 to
      15% in 2002) than female daily smoking (34% in 1976 to 20% in 2002) in Sweden,
      with a substantial proportion (around 30%) of male ex-smokers using snus when
      quitting smoking. Over the same time period, rates of lung cancer and myocardial
      infarction have dropped significantly faster among Swedish men than women and
      remain at low levels as compared with other developed countries with a long
      history of tobacco use. CONCLUSIONS: Snus availability in Sweden appears to have
      contributed to the unusually low rates of smoking among Swedish men by helping
      them transfer to a notably less harmful form of nicotine dependence.

PMID- 14660767
TI  - European Union policy on smokeless tobacco: a statement in favour of evidence
      based regulation for public health.
AB  - RATIONALE: This statement is an updated version of one released by the same
      authors in February 2003. The statement was produced to follow up the Royal
      College of Physicians (RCP) Tobacco Advisory Group report "Protecting smokers,
      saving lives: the case for a tobacco and nicotine regulatory authority", which
      argued for an evidence based regulatory approach to smokeless tobacco and harm
      reduction and posed a series of questions that regulators must address in
      relation to smokeless tobacco. The purpose of this statement is to provide
      arguments of fact and principle to follow the RCP's report and to outline the
      public health case for changing existing European Union (EU) regulation in this
      area. A review of regulation in relation to harm reduction and regulation of
      tobacco products other than cigarettes is required in Article 11 of EU directive
      2001/37/EC, and this is a contribution towards forming a consensus in the
      European public health community about what policy the EU should adopt in the
      light of this review, or following ongoing legal action that may potentially
      strike out the existing regulation altogether. PUBLIC HEALTH CASE: We believe
      that the partial ban applied to some forms of smokeless tobacco in the EU should
      be replaced by regulation of the toxicity of all smokeless tobacco. We hold this
      view for public health reasons: smokeless tobacco is substantially less harmful
      than smoking and evidence from Sweden suggests it is used as a substitute for
      smoking and for smoking cessation. To the extent there is a "gateway" it appears
      not to lead to smoking, but away from it and is an important reason why Sweden
      has the lowest rates of tobacco related disease in Europe. We think it is wrong
      to deny other Europeans this option for risk reduction and that the current ban
      violates rights of smokers to control their own risks. For smokers that are
      addicted to nicotine and cannot or will not stop, it is important that they can
      take advantage of much less hazardous forms of nicotine and tobacco-the
      alternative being to "quit or die". and many die. While nicotine replacement
      therapies (NRT) may have a role in harm reduction, tobacco based harm reduction
      options may reach more smokers and in a different, market based, way. Chewing
      tobacco is not banned or regulated in the EU but is often highly toxic, and our
      proposal could remove more products from the market than it permitted. REGULATORY
      OPTIONS: We believe that the EU policy on smokeless tobacco should adapt to new
      scientific knowledge and that the European Commission should bring forward
      proposals to amend or replace Article 8 of directive 2001/37/EC with a new
      regulatory framework. Canada has developed testing regimens for tobacco
      constituents and these could be readily adapted to the European situation. A
      review of EU policy in this area is required no later than December 2004, and we
      believe the Commission should expedite the part of its review that deals with
      harm reduction and regulation of tobacco products other than cigarettes so as to
      reconsider its policy on smokeless tobacco. We held this view before Swedish
      Match brought its legal proceedings to challenge EU legislation and we will
      continue to hold these views if its action fails.

PMID- 14660769
TI  - Declining smoking in Sweden: is Swedish Match getting the credit for Swedish
      tobacco control's efforts?

PMID- 14660770
TI  - Some practical points on harm reduction: what to tell your lawmaker and what to
      tell your brother about Swedish snus.

PMID- 14660771
TI  - A strategy for controlling the marketing of tobacco products: a regulated market
      model.
AB  - OBJECTIVE: To outline a novel strategy for controlling the tobacco market.
      ARGUMENTS: More comprehensive controls over the tobacco market are essential and
      long overdue. Effective controls need to encourage the development of less
      harmful products; control commercial communication to ensure that potential harms
      are highlighted relative to any benefits; and provide mechanisms to move
      consumers away from tobacco use, or at least towards less harmful alternatives.
      Achieving this by regulating the existing industry is one strategy. This paper
      puts the case for an alternative: to have marketing controlled by an agency
      (called here the Tobacco Products Agency, or TPA) which tendered to manufacturers
      for product and which distributed to retailers in ways that reduce incentives to
      bend or break the law. The TPA would be backed by legislation that made tobacco a
      controlled substance with possession sale and use only allowed as permitted by
      the regulations, which in reality would be only as provided by the TPA.
      CONCLUSIONS: The overall effect of such a model, which we call a "regulated
      market model", would be to eliminate most of the incentives and remaining
      opportunities for commercial promotion of tobacco and to create incentives to
      encourage the development of less harmful tobacco products. Such a model
      preserves the competition inherent in a free market, but directs it towards the
      challenge of reducing the harm from tobacco use.

PMID- 14660773
TI  - The US tobacco control community's view of the future of tobacco harm reduction.
AB  - OBJECTIVE: Tobacco harm reduction (THR) has garnered recent attention due to the
      introduction of novel nicotine delivery products ostensibly intended to reduce
      risk for inveterate cigarette smokers. This study evaluates the grassroots
      tobacco control community's knowledge, opinions, and beliefs about THR. DESIGN: A
      web/mail survey conducted in October and November 2002, with a telephone survey
      of a sample of non-respondents. SUBJECTS: The 2833 US based registrants for the
      2001 National Conference on Tobacco or Health. MAIN OUTCOME MEASURES:
      Respondents' awareness of THR, perception of its importance, support for
      regulation, and perception of which THR products should be recommended to
      inveterate cigarette smokers. RESULTS: 70% of respondents were aware of THR but
      respondents had low recognition of specific products at the forefront of the
      debate, such as Swedish snuff. Half believe THR will reduce smoking cessation and
      cause nicotine experimentation by children; 63% anticipate unintended adverse
      side effects. More expect THR to have a negative than a positive impact on
      health. Large majorities support government regulation of THR and conventional
      tobacco products, but fewer than 30% expect legislation regulating either. Most
      would recommend nicotine patches (76%) and gum (70%) to inveterate smokers, but
      no other product was supported by a majority. Scientists are more supportive of
      THR than activists, while respondents focusing on national/international issues
      are more supportive than those concentrating on local/state issues. CONCLUSIONS:
      Many members of the US tobacco control community are unaware of the THR
      "movement", while others possess only rudimentary familiarity with it. If and as
      THR achieves an increasingly prominent role on the tobacco-or-health scene, this
      community will have to become educated about THR, and be prepared to advocate for
      regulatory policies that will maximise the potential for positive outcomes. The
      potential for negative outcomes remains significant.

PMID- 14660774
TI  - Impact of the graphic Canadian warning labels on adult smoking behaviour.
AB  - OBJECTIVE: To assess the impact of graphic Canadian cigarette warning labels on
      current adult smokers. DESIGN: A random-digit-dial telephone survey was conducted
      with 616 adult smokers in south western Ontario, Canada in October/November 2001,
      with three month follow up. MAIN OUTCOME MEASURES: Smoking behaviour (quitting,
      quit attempts, and reduced smoking), intentions to quit, and salience of the
      warning labels. RESULTS: Virtually all smokers (91%) reported having read the
      warning labels and smokers demonstrated a thorough knowledge of their content. A
      strong positive relation was observed between a measure of cognitive processing
      the extent to which smokers reported reading, thinking about, and discussing the
      new labels-and smokers' intentions to quit (odds ratio (OR) 1.11, 95% confidence
      interval (CI) 1.07 to 1.16; p < 0.001). Most important, cognitive processing
      predicted cessation behaviour at follow up. Smokers who had read, thought about,
      and discussed the new labels at baseline were more likely to have quit, made a
      quit attempt, or reduced their smoking three months later, after adjusting for
      intentions to quit and smoking status at baseline (OR 1.07, 95% CI 1.03 to 1.12;
      p < 0.001). CONCLUSIONS: Graphic cigarette warning labels serve as an effective
      population based smoking cessation intervention. The findings add to the growing
      literature on health warnings and provide strong support for the effectiveness of
      Canada's tobacco labelling policy.

PMID- 14660775
TI  - What the public thinks about the tobacco industry and its products.
AB  - OBJECTIVES: To assess public attitudes toward the tobacco industry and its
      products, and to identify predictors of attitudes supportive of tobacco industry
      denormalisation. DESIGN: Population based, cross sectional survey. SETTING:
      Ontario, Canada. SUBJECTS: Adult population (n = 1607). MAIN OUTCOME MEASURES:
      Eight different facets of tobacco industry denormalisation were assessed. A
      denormalisation scale was developed to examine predictors of attitudes supportive
      of tobacco industry denormalisation, using bivariate and multivariate analyses.
      RESULTS: Attitudes to the eight facets of tobacco industry denormalisation varied
      widely. More than half of the respondents supported regulating tobacco as a
      hazardous product, fining the tobacco industry for earnings from underage
      smoking, and suing tobacco companies for health care costs caused by tobacco.
      Majorities also thought that the tobacco industry is dishonest and that
      cigarettes are too dangerous to be sold at all. Fewer than half of the
      respondents thought that the tobacco industry is mostly or completely responsible
      for the health problems smokers have because of smoking and that tobacco
      companies should be sued for taxes lost from smuggling. In particular, less than
      a quarter thought that the tobacco industry is most responsible for young people
      starting to smoke. Non-smoking, knowledge about health effects caused by tobacco,
      and support for the role of government in health promotion were independent
      predictors of support for tobacco industry denormalisation. CONCLUSIONS: Although
      Ontarians are ambivalent toward tobacco industry denormalisation, they are
      supportive of some measures. Mass media programmes aimed at increasing support
      for tobacco industry denormalisation and continued monitoring of public attitudes
      toward this strategy are needed.

PMID- 14660776
TI  - A comparison of US and Norwegian regulation of coumarin in tobacco products.
AB  - OBJECTIVE: This paper examines policy processes regarding why the USA and Norway
      have not regulated coumarin in tobacco. DESIGN: A qualitative analysis of all
      tobacco industry documents regarding coumarin since the 1950s from the 1998 US
      Master Settlement Agreement and subsequent legal settlements. Additional data
      were collected from newspaper reports, general internet search engines, journal
      articles, scholarly reports, court cases, statutes, regulations, and informal
      correspondence with tobacco control experts in Norway. MAIN OUTCOME MEASURE: An
      overview, summary, and analysis of all documents related to coumarin. RESULTS: In
      the USA from 1954 until 1985 when coumarin was reportedly removed from domestic
      cigarettes, but not from pipe tobacco until 1996, and not at all from imported
      Indian bidi cigarettes, regulatory efforts were stymied. In Norway, from 1973 to
      the present, the tobacco industry has never disclosed whether its tobacco
      products contain coumarin. In both the USA and Norway, the extreme delay and lack
      of vigorous evidence gathering and significant remedies were caused by tobacco
      industry assertions that revealing tobacco additives was a violation of trade
      secrets, and by weak regulatory authority and efforts to regulate coumarin.
      CONCLUSION: Vigorous and expeditious regulatory investigations and remedies for
      harmful additives in tobacco, such as coumarin, can protect the public health.
      Astute insider and outsider political advocacy by health advocates is required to
      hold elected officials and civil servants publicly accountable for failing to
      enact disclosure laws and to engage in effective regulatory efforts.

PMID- 14660777
TI  - Hand rolling cigarette papers as the reference point for regulating cigarette
      fire safety.
AB  - AIM: To compare the burning characteristics of the tobacco and paper of
      manufactured and hand rolled cigarettes, and set a fire safety standard of
      manufacture to largely reduce the fire risk from discarded cigarettes. METHODS:
      (1) Cigarette extinction test of ignition strength: 40 cigarettes per brand, lit
      and placed on 15 layers of filter paper, in accordance with ASTM test standard
      E2187-02. (2) Citrate extracted by 0.1N hydrochloric acid from cigarette papers
      and from tobacco in manufactured cigarettes, the supernatant analysed by high
      performance liquid chromatography using ultraviolet visual light
      spectrophotometer. (3) Survey of 750 nationally representative adults age 18
      years and over, by telephone, including 184 smokers. MATERIALS: (a) New Zealand
      made Holiday, and Horizon, and US made Marlboro manufactured cigarettes; (b) US
      manufactured Merit with banded paper; (c) Holiday, Horizon and Marlboro hand
      rolling tobaccos, hand rolled in Rizla cigarette papers; (d) manufactured
      cigarettes as in (a), reconstructed using Rizla hand rolling cigarette papers.
      RESULTS: 1. (a) For each brand of manufactured cigarettes, 40/40 burnt full
      length; (b) for Merit banded paper cigarettes 29/40 (73%) burnt full length; (c)
      for each brand of hand rolled cigarettes 0/40 burnt full length; (d) 0/40
      manufactured cigarettes reconstructed with Rizla hand rolling paper burnt full
      length. 2. Citrate content: (a) In manufactured cigarette papers: 0.3-0.8 mg; in
      tobacco of manufactured cigarettes: Holiday 0, Horizon 0, Marlboro 8.8 mg; (b)
      Merit: in banded paper 0.418 mg; in tobacco 10.23 mg; (c) In hand rolled
      cigarettes: in the papers < 0.08 mg; in hand rolled tobacco 13.3-15.0 mg; (d) In
      hand rolling papers of reconstructed cigarettes: < 0.018 mg. 3. Requiring
      manufactured cigarettes to compulsorily self-extinguish when left unattended was
      supported by 67% of smokers, 61% of manufactured cigarette smokers, 82% of hand
      rolled smokers, and by 68% of non-smokers. CONCLUSION: The wrapping paper is a
      key determinant of whether or not unpuffed cigarettes burn their full length.
      Using international test methods, popular brands of manufactured cigarettes all
      burnt full length, but none did so when re-wrapped in hand rolling cigarette
      paper. This provides a ready-to-hand smoker acceptable standard for reducing
      ignition potential from manufactured cigarettes, as a basis for regulation or
      litigation.

PMID- 14660778
TI  - No association of smoke-free ordinances with profits from bingo and charitable
      games in Massachusetts.
AB  - BACKGROUND: Because it is widely played, claims that smoking restrictions will
      adversely affect bingo games is used as an argument against these policies. We
      used publicly available data from Massachusetts to assess the impact of 100%
      smoke-free ordinances on profits from bingo and other gambling sponsored by
      charitable organisations between 1985 and 2001. METHODS: We conducted two
      analyses: (1) a general linear model implementation of a time series analysis
      with net profits (adjusted to 2001 dollars) as the dependent variable, and
      community (as a fixed effect), year, lagged net profits, and the length of time
      the ordinance had been in force as the independent variables; (2) multiple linear
      regression of total state profits against time, lagged profits, and the
      percentage of the entire state population in communities that allow charitable
      gaming but prohibit smoking. RESULTS: The general linear model analysis of data
      from individual communities showed that, while adjusted profits fell over time,
      this effect was not related to the presence of an ordinance. The analysis in
      terms of the fraction of the population living in communities with ordinances
      yielded the same result. CONCLUSION: Policymakers can implement smoke-free
      policies without concern that these policies will affect charitable gaming.

PMID- 14660780
TI  - Tobacco industry strategy to undermine tobacco control in Finland.
AB  - OBJECTIVE: To identify and explain tobacco industry strategy in undermining
      tobacco control measures in Finland and results of these interferences in tobacco
      policy development during the 1980s and early 1990s. METHODS: Tobacco industry
      documents, which have been publicly available on the internet as a result of
      litigation in the USA, were analysed. Documents were sought by Finland and by
      names of organisations and tobacco control activists. Documents were accessed and
      assessed between September 2000 and November 2002. Tactics of the tobacco
      industry activities were categorised as presented by Saloojee and Dagli. RESULTS:
      The international tobacco companies utilised similar strategies in Finland as in
      other industrial markets to fight tobacco control and legislation, the health
      advocacy movement, and litigation. These activities slowed down the development
      and implementation of the Tobacco Act in Finland. However, despite the extensive
      pressure, the industry was not able to prevent the most progressive tobacco
      legislation in Europe from being passed and coming into force in Finland in 1977
      and in 1995. CONCLUSION: Denying the health hazards caused by tobacco-despite
      indisputable scientific evidence-decreased the credibility of the tobacco
      industry. Strategy of denial was falsely chosen, as health advocacy groups were
      active both in society and the parliamentary system. The strong influence of the
      tobacco industry may have in fact increased the visibility of tobacco control in
      Finland as the litigation process was also drawing attention to negative health
      effects of tobacco. Therefore the tobacco industry did not manage to convince
      public opinion. However, the tobacco industry did obtain experience in Finland in
      how to object to tobacco control measures.

PMID- 14660781
TI  - Application of toxicological risk assessment principles to the chemical
      constituents of cigarette smoke.
AB  - OBJECTIVE: To provide a hazard prioritisation for reported chemical constituents
      of cigarette smoke using toxicological risk assessment principles and
      assumptions. The purpose is to inform prevention efforts using harm reduction.
      DATA SOURCES: International Agency for Research on Cancer Monographs; California
      and US Environmental Protection Agency cancer potency factors (CPFs) and
      reference exposure levels; scientific journals and government reports from the
      USA, Canada, and New Zealand. STUDY SELECTION: This was an inclusive review of
      studies reporting yields of cigarette smoke constituents using standard ISO
      methods. DATA EXTRACTION: Where possible, the midpoint of reported ranges of
      yields was used. DATA SYNTHESIS: Data on 158 compounds in cigarette smoke were
      found. Of these, 45 were known or suspected human carcinogens. Cancer potency
      factors were available for 40 of these compounds and reference exposure levels
      (RELs) for non-cancer effects were found for 17. A cancer risk index (CRI) was
      calculated by multiplying yield levels with CPFs. A non-cancer risk index (NCRI)
      was calculated by dividing yield levels with RELs. Gas phase constituents
      dominate both CRI and NCRI for cigarette smoke. The contribution of 1,3-butadiene
      (BDE) to CRI was more than twice that of the next highest contributing carcinogen
      (acrylonitrile) using potencies from the State of California EPA. Using those
      potencies from the USEPA, BDE ranked third behind arsenic and acetaldehyde. A
      comparison of CRI estimates with estimates of smoking related cancer deaths in
      the USA showed that the CRI underestimates the observed cancer rates by about
      fivefold using ISO yields in the exposure estimate. CONCLUSIONS: The application
      of toxicological risk assessment methods to cigarette smoke provides a plausible
      and objective framework for the prioritisation of carcinogens and other toxicant
      hazards in cigarette smoke. However, this framework does not enable the
      prediction of actual cancer risk for a number of reasons that are discussed.
      Further, the lack of toxicology data on cardiovascular end points for specific
      chemicals makes the use of this framework less useful for cardiovascular
      toxicity. The bases for these priorities need to be constantly re-evaluated as
      new toxicology information emerges.

PMID- 14660782
TI  - Bhutan: the world's most advanced tobacco control nation?
AB  - Significant achievements in the area of tobacco control have been made in the
      kingdom of Bhutan in the Eastern Himalayas, following the initiation of several
      tobacco control activities.

PMID- 14660784
TI  - Are there socioeconomic differentials in under-reporting of smoking in pregnancy?

PMID- 14660785
TI  - Tobacco use in India: prevalence and predictors of smoking and chewing in a
      national cross sectional household survey.
AB  - OBJECTIVE: To estimate the prevalence and the socioeconomic and demographic
      correlates of tobacco consumption in India. DESIGN: Cross sectional, nationally
      representative population based household survey. SUBJECTS: 315 598 individuals
      15 years or older from 91 196 households were sampled in National Family Health
      Survey-2 (1998-99). Data on tobacco consumption were elicited from household
      informants. Measures and methods: Prevalence of current smoking and current
      chewing of tobacco were used as outcome measures. Simple and two way cross
      tabulations and multivariate logistic regression analysis were the main
      analytical methods. RESULTS: Thirty per cent of the population 15 years or older
      47% men and 14% of women-either smoked or chewed tobacco, which translates to
      almost 195 million people-154 million men and 41 million women in India. However,
      the prevalence may be underestimated by almost 11% and 1.5% for chewing tobacco
      among men and women, respectively, and by 5% and 0.5% for smoking among men and
      women, respectively, because of use of household informants. Tobacco consumption
      was significantly higher in poor, less educated, scheduled castes and scheduled
      tribe populations. The prevalence of tobacco consumption increased up to the age
      of 50 years and then levelled or declined. The prevalence of smoking and chewing
      also varied widely between different states and had a strong association with
      individual's sociocultural characteristics. CONCLUSION: The findings of the study
      highlight that an agenda to improve health outcomes among the poor in India must
      include effective interventions to control tobacco use. Failure to do so would
      most likely result in doubling the burden of diseases-both communicable and non
      communicable-among India's teeming poor. There is a need for periodical surveys
      using more consistent definitions of tobacco use and eliciting information on
      different types of tobacco consumed. The study also suggests a need to adjust the
      prevalence estimates based on household informants.

PMID- 14660786
TI  - Increased hippocampal neurogenesis in Alzheimer's disease.
AB  - Neurogenesis, which persists in the adult mammalian brain, may provide a basis
      for neuronal replacement therapy in neurodegenerative diseases like Alzheimer's
      disease (AD). Neurogenesis is increased in certain acute neurological disorders,
      such as ischemia and epilepsy, but the effect of more chronic neurodegenerations
      is uncertain, and some animal models of AD show impaired neurogenesis. To
      determine how neurogenesis is affected in the brains of patients with AD, we
      investigated the expression of immature neuronal marker proteins that signal the
      birth of new neurons in the hippocampus of AD patients. Compared to controls,
      Alzheimer's brains showed increased expression of doublecortin, polysialylated
      nerve cell adhesion molecule, neurogenic differentiation factor and TUC-4.
      Expression of doublecortin and TUC-4 was associated with neurons in the
      neuroproliferative (subgranular) zone of the dentate gyrus, the physiological
      destination of these neurons (granule cell layer), and the CA1 region of Ammon's
      horn, which is the principal site of hippocampal pathology in AD. These findings
      suggest that neurogenesis is increased in AD hippocampus, where it may give rise
      to cells that replace neurons lost in the disease, and that stimulating
      hippocampal neurogenesis might provide a new treatment strategy.

PMID- 14660787
TI  - A discrete water exit pathway in the membrane protein cytochrome c oxidase.
AB  - By using the non-redox-active Mg2+/Mn2+ site of cytochrome c oxidase as a probe,
      water access from the outside of the enzyme and water escape from the buried
      active site were studied. Water movement was time-resolved by monitoring the
      magnetic interaction of the oxygen isotope 17O with the Mn2+ by using a rapid
      freeze-quench-electron spin echo envelope modulation technique. Rapid (msec)
      access of water from the bulk phase to the Mn2+ was demonstrated by mixing
      cytochrome c oxidase with H217O. To determine whether a channel involving the
      Mn2+ was used for water exit from the active site, samples incubated in 17O2 were
      allowed to turn over approximately five times before freezing. The 17O, now in
      the form of H217O, was detected at the Mn2+. The significant broadening of the
      Mn2+ signal after the limited number of turnovers strongly suggests that the
      water exits the protein by means of one discrete pathway, not by random
      diffusion.

PMID- 14660788
TI  - Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes
      insulin resistance in fat and liver but not in muscle.
AB  - Syndrome X, typified by obesity, insulin resistance (IR), dyslipidemia, and other
      metabolic abnormalities, is responsive to antidiabetic thiazolidinediones (TZDs).
      Peroxisome proliferator-activated receptor (PPAR) gamma, a target of TZDs, is
      expressed abundantly in adipocytes, suggesting an important role for this tissue
      in the etiology and treatment of IR. Targeted deletion of PPARgamma in adipose
      tissue resulted in marked adipocyte hypocellularity and hypertrophy, elevated
      levels of plasma free fatty acids and triglyceride, and decreased levels of
      plasma leptin and ACRP30. In addition, increased hepatic glucogenesis and IR were
      observed. Despite these defects, blood glucose, glucose and insulin tolerance,
      and insulin-stimulated muscle glucose uptake were all comparable to those of
      control mice. However, targeted mice were significantly more susceptible to high
      fat diet-induced steatosis, hyperinsulinemia, and IR. Surprisingly, TZD treatment
      effectively reversed liver IR, whereas it failed to lower plasma free fatty
      acids. These results suggest that syndrome X may be comprised of separable
      PPARgamma-dependent components whose origins and therapeutic sites may reside in
      distinct tissues.

PMID- 14660789
TI  - Cellular and nerve regeneration within a biosynthetic extracellular matrix for
      corneal transplantation.
AB  - Our objective was to determine whether key properties of extracellular matrix
      (ECM) macromolecules can be replicated within tissue-engineered biosynthetic
      matrices to influence cellular properties and behavior. To achieve this, hydrated
      collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and
      tested on a corneal model. The structural and immunological simplicity of the
      cornea and importance of its extensive innervation for optimal functioning makes
      it an ideal test model. In addition, corneal failure is a clinically significant
      problem. Matrices were therefore designed to have the optical clarity and the
      proper dimensions, curvature, and biomechanical properties for use as corneal
      tissue replacements in transplantation. In vitro studies demonstrated that
      grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels
      promoted epithelial stratification and neurite in-growth. Implants into pigs'
      corneas demonstrated successful in vivo regeneration of host corneal epithelium,
      stroma, and nerves. In particular, functional nerves were observed to rapidly
      regenerate in implants. By comparison, nerve regeneration in allograft controls
      was too slow to be observed during the experimental period, consistent with the
      behavior of human cornea transplants. Other corneal substitutes have been
      produced and tested, but here we report an implantable matrix that performs as a
      physiologically functional tissue substitute and not simply as a prosthetic
      device. These biosynthetic ECM replacements should have applicability to many
      areas of tissue engineering and regenerative medicine, especially where nerve
      function is required.

PMID- 14660790
TI  - Widespread purifying selection at polymorphic sites in human protein-coding loci.
AB  - Estimation of gene diversity (heterozygosity) at 1442 single-nucleotide
      polymorphism (SNP) loci in an ethnically diverse sample of humans revealed
      consistently reduced gene diversities at SNP loci causing amino acid changes,
      particularly those causing amino acid changes predicted to be disruptive to
      protein structure. The reduction of gene diversity at these SNP loci, in
      comparison to SNPs in the same genes not affecting protein structure, is evidence
      that negative natural selection (purifying selection) has reduced the population
      frequencies of deleterious SNP alleles. This, in turn, suggests that slightly
      deleterious mutations are widespread in the human population and that estimation
      of gene diversity even in a sample of modest size can help guide the search for
      disease-associated genes.

PMID- 14660791
TI  - The tetraspanin CD63 enhances the internalization of the H,K-ATPase beta-subunit.
AB  - The tetraspanin CD63 resides in late endosomes, lysosomes, secretory vesicles,
      and at the plasma membrane, and it moves among these compartments. We find that
      CD63 is present also in tubulovesicular elements, the intracellular compartments
      that contain the H,K-ATPase in unstimulated gastric parietal cells. The H,K
      ATPase beta-subunit and CD63 colocalize in parietal cells and form a complex that
      can be coprecipitated. The beta-subunit and CD63 also interact when they are
      coexpressed in COS-7 cells. Furthermore, expression with CD63 induces the
      redistribution of the beta-subunit from the cell surface to CD63+ intracellular
      compartments. Immunofluorescence and biochemical experiments reveal that this
      redistribution occurs by enhanced endocytosis of H,K-ATPase beta-subunit
      complexed with CD63. Coexpression of the beta-subunit with mutant CD63
      polypeptides demonstrates that the enhanced internalization of the beta-subunit
      depends on the capacity of CD63 to interact with adaptor protein complexes 2 and
      3. These data indicate that CD63 serves as an adaptor protein that links its
      interaction partners to the endocytic machinery of the cell and suggest a
      previously uncharacterized protein-trafficking role for the tetraspanins.

PMID- 14660792
TI  - Organismal complexity, protein complexity, and gene duplicability.
AB  - Although the evolutionary significance of gene duplication has long been
      recognized, it remains unclear what determines gene duplicability. We find
      protein complexity to be an important determinant because the proportion of
      unduplicated genes (P) increases with the number of subunits in a protein.
      However, P is high (>or=65%) for both monomers and multimers in yeast, but
      <or=30% in human except for subunits of large multimers, implying that organismal
      complexity is a stronger determinant of gene duplicability than protein
      complexity. The same conclusion is reached from a comparison of family sizes in
      yeast and human.

PMID- 14660793
TI  - Phylogenetic and biochemical evidence for sterol synthesis in the bacterium
      Gemmata obscuriglobus.
AB  - Sterol biosynthesis is viewed primarily as a eukaryotic process, and the
      frequency of its occurrence in bacteria has long been a subject of controversy.
      Two enzymes, squalene monooxygenase and oxidosqualene cyclase, are the minimum
      necessary for initial biosynthesis of sterols from squalene. In this work, 19
      protein gene sequences for eukaryotic squalene monooxygenase and 12 protein gene
      sequences for eukaryotic oxidosqualene cyclase were compared with all available
      complete and partial prokaryotic genomes. The only unequivocal matches for a
      sterol biosynthetic pathway were in the proteobacterium, Methylococcus
      capsulatus, in which sterol biosynthesis is known, and in the planctomycete,
      Gemmata obscuriglobus. The latter species contains the most abbreviated sterol
      pathway yet identified in any organism. Analysis shows that the major sterols in
      Gemmata are lanosterol and its uncommon isomer, parkeol. There are no subsequent
      modifications of these products. In bacteria, the sterol biosynthesis genes
      occupy a contiguous coding region and possibly comprise a single operon.
      Phylogenetic trees constructed for both enzymes show that the sterol pathway in
      bacteria and eukaryotes has a common ancestry. It is likely that this contiguous
      reading frame was exchanged between bacteria and early eukaryotes via lateral
      gene transfer or endosymbiotic events. The primitive sterols produced by Gemmata
      suggest that this genus could retain the most ancient remnants of the sterol
      biosynthetic pathway.

PMID- 14660794
TI  - Inhibition of mutant p53 expression and growth of DMS-153 small cell lung
      carcinoma by antagonists of growth hormone-releasing hormone and bombesin.
AB  - We investigated the effects of growth hormone-releasing hormone (GHRH)
      antagonists, JV-1-65 and JV-1-63, and bombesin/gastrin-releasing peptide (BN/GRP)
      antagonist RC-3940-II on DMS-153 human small cell lung carcinoma xenografted into
      nude mice. Treatment with 10 microg/day JV-1-65 or RC-3940-II decreased tumor
      volume by 28% (P < 0.05) and 77% (P < 0.01), respectively, after 42 days compared
      with controls. Combination of JV-1-65 and RC-3940-II induced the greatest
      inhibition of tumor proliferation (95%; P < 0.01), suggesting a synergism.
      Western blotting showed that the antitumor effects of these antagonists were
      associated with inhibition of the expression of the mutant tumor suppressor
      protein p53 (Tp53). Mutation was detected by sequence analysis of the p53 gene at
      codon 155: ACC [Thr] --> CCC [Pro]. Combination of JV-1-65 and RC-3940-II
      decreased the levels of mutant p53 protein by 42% (P < 0.01) compared with
      controls. JV-1-65, JV-1-63, and RC-3940-II, given singly, reduced mutant p53
      protein expression by 18-24% (P < 0.05). Serum insulin-like growth factor (IGF)-I
      levels were diminished in animals receiving GHRH antagonists. mRNA levels for IGF
      II, IGF receptor-I, GRP receptor, and EGF receptor in tumors were significantly
      decreased by combined treatment with JV-1-65 and RC-3940-II. DMS-153 tumors
      expressed mRNAs for GHRH and GHRH receptor splice variants 1 and 2, suggesting
      that GHRH could be an autocrine growth factor. Proliferation of DMS-153 cells in
      vitro was stimulated by GRP and IGF-II and inhibited by JV-1-65. This study
      indicates that GHRH antagonists and BN/GRP antagonist inhibit the growth of DMS
      153 small cell lung carcinoma concomitantly with the expression of mutant Tp53,
      which might uncouple the signal transduction pathways for cell growth
      stimulation.

PMID- 14660795
TI  - Mono- and multisite phosphorylation enhances Bcl2's antiapoptotic function and
      inhibition of cell cycle entry functions.
AB  - Bcl2 functions to suppress apoptosis and retard cell cycle entry. Single-site
      phosphorylation at serine 70 (S70) is required for Bcl2's antiapoptotic function,
      and multisite phosphorylation at threonine 69 (T69), S70, and S87 has been
      reported to inactivate Bcl2. To address this apparent conflict and identify the
      regulatory role for Bcl2 phosphorylation in cell death and cell cycle control, a
      series of serine/threonine (S/T) --> glutamate/alanine (E/A) mutants including
      T69E/A, S70E/A, S87E/A, T69E/S70A/S87A (EAA), T69A/S70E/S87A (AEA),
      T69A/S70A/S87E (AAE), T69E/S70E/S87E (EEE), and T69A/S70A/S87A (AAA) was created
      to mimic or abrogate, respectively, either single-site or multisite
      phosphorylation. The survival and cell cycle status of cells expressing the
      phosphomimetic or nonphosphorylatable Bcl2 mutants were compared. Surprisingly,
      all of the E but not the A Bcl2 mutants potently enhance cell survival after
      stress and retard G(1)/S cell cycle transition. The EEE Bcl2 mutant is the most
      potent, indicating a possible cumulative advantage for multisite phosphorylation
      of Bcl2 in survival and retardation of G(1)/S transition functions. Because the E
      containing Bcl2 mutants, but not the A-containing mutants, can more potently
      block cytochrome c release from mitochondria during apoptotic stress, even at
      times when steady-state expression levels are similar for all mutants, we
      conclude that phosphorylation at one or multiple sites within the flexible loop
      domain of Bcl2 not only stimulates antiapoptotic activity but also can regulate
      cell cycle entry.

PMID- 14660796
TI  - Plastid protein synthesis is required for plant development in tobacco.
AB  - Chloroplasts fulfill important functions in cellular metabolism. The majority of
      plastid genome-encoded genes is involved in either photosynthesis or chloroplast
      gene expression. Whether or not plastid genes also can determine extraplastidic
      functions has remained controversial. We demonstrate here an essential role of
      plastid protein synthesis in tobacco leaf development. By using chloroplast
      transformation, we have developed an experimental system that produces
      recombination-based knockouts of chloroplast translation in a cell-line-specific
      manner. The resulting plants are chimeric and, in the presence of translational
      inhibitors, exhibit severe developmental abnormalities. In the absence of active
      plastid protein synthesis, leaf blade development is abolished because of an
      apparent arrest of cell division. This effect appears to be cell-autonomous in
      that adjacent sectors of cells with translating plastids are phenotypically
      normal but cannot complement for the absence of plastid translation in mutant
      sectors. Developmental abnormalities also are seen in flower morphology,
      indicating that the defects are not caused by inhibited expression of plastid
      photosynthesis genes. Taken together, our data point to an unexpected essential
      role of plastid genes and gene expression in plant development and cell division.

PMID- 14660797
TI  - Altered starch structure is associated with endosperm modification in Quality
      Protein Maize.
AB  - The biochemical basis of modified kernel texture in Quality Protein Maize (QPM)
      is poorly understood. Proteomic analysis of several QPM lines indicated increased
      levels of granule-bound starch synthase I in the soluble nonzein protein fraction
      of these genotypes. Increased extraction of this enzyme reflected a change in
      starch structure, which was manifested as shorter amylopectin branches and
      increased starch-granule swelling. In mature kernels, these alterations in starch
      structure were associated with interconnections between starch granules that
      resulted in a vitreous kernel phenotype. Understanding the molecular basis for
      this previously uncharacterized starch structure will accelerate the development
      of QPM.

PMID- 14660798
TI  - Extensive gene gain associated with adaptive evolution of poxviruses.
AB  - Previous studies of genome evolution usually have involved one or two genomes and
      have thus been limited in their ability to detect the direction and rate of
      evolutionary change. Here, we use complete genome data from 20 poxvirus genomes
      to build a robust phylogeny of the Poxviridae and to study patterns of genome
      evolution. We show that, although there has been little gene order evolution,
      there are substantial differences between poxviruses in terms of genome content.
      Furthermore, we show that the rate of gene acquisition is not constant over time
      and that it has increased in the orthopox lineage (which includes smallpox and
      vaccinia). We also tested for positive selection on 204 groups of genes and show
      that a disproportionately high proportion of genes in the orthopox clade are
      under positive selection. The association of an increased rate of gene gain and
      positive selection is indicative of adaptive genome evolution. Many of the genes
      involved in these processes are likely to be associated with host-parasite
      coevolution.

PMID- 14660799
TI  - A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the
      protein defective in Batten disease.
AB  - In Saccharomyces cerevisiae, transport of arginine into the vacuole has
      previously been shown to be facilitated by a putative H+/arginine antiport. We
      confirm that transport of arginine into isolated yeast vacuoles requires ATP and
      we demonstrate a requirement for a functional vacuolar H+-ATPase. We previously
      reported that deletion of BTN1 (btn1-delta), an ortholog of the human Batten
      disease gene CLN3, resulted in a decrease in vacuolar pH during early growth. We
      report that this altered vacuolar pH in btn1-delta strains underlies a lack of
      arginine transport into the vacuole, which results in a depletion of endogenous
      vacuolar arginine levels. This arginine transport defect in btn1-delta is
      complemented by expression of either BTN1 or the human CLN3 gene and strongly
      suggests a function for transport of, or regulation of the transport of, basic
      amino acids into the vacuole or lysosome for yeast Btn1p, and human CLN3 protein,
      respectively. We propose that defective transport at the lysosomal membrane
      caused by an absence of functional CLN3 is the primary biochemical defect that
      results in Batten disease.

PMID- 14660800
TI  - A pointwise estimate for fractionary derivatives with applications to partial
      differential equations.
AB  - This article emphasizes the role played by a remarkable pointwise inequality
      satisfied by fractionary derivatives in order to obtain maximum principles and Lp
      decay of solutions of several interesting partial differential equations. In
      particular, there are applications to quasigeostrophic flows, in two space
      variables with critical viscosity, that model the Eckman pumping [see Baroud, Ch.
      N., Plapp, B. B., She, Z. S. & Swinney, H. L. (2002) Phys. Rev. Lett. 88, 114501
      and Constantin, P. (2002) Phys. Rev. Lett. 89, 184501].

PMID- 14660801
TI  - Distinct light-mediated pathways regulate the biosynthesis and exchange of
      isoprenoid precursors during Arabidopsis seedling development.
AB  - Plants synthesize an astonishing diversity of isoprenoids, some of which play
      essential roles in photosynthesis, respiration, and the regulation of growth and
      development. Two independent pathways for the biosynthesis of isoprenoid
      precursors coexist within the plant cell: the cytosolic mevalonic acid (MVA)
      pathway and the plastidial methylerythritol phosphate (MEP) pathway. In at least
      some plants (including Arabidopsis), common precursors are exchanged between the
      cytosol and the plastid. However, little is known about the signals that
      coordinate their biosynthesis and exchange. To identify such signals, we arrested
      seedling development by specifically blocking the MVA pathway with mevinolin
      (MEV) or the MEP pathway with fosmidomycin (FSM) and searched for MEV-resistant
      Arabidopsis mutants that also could survive in the presence of FSM. Here, we show
      that one such mutant, rim1, is a new phyB allele (phyB-m1). Although the MEV
      resistant phenotype of mutant seedlings is caused by the upregulation of MVA
      synthesis, its resistance to FSM most likely is the result of an enhanced intake
      of MVA-derived isoprenoid precursors by the plastid. The analysis of other light
      hyposensitive mutants showed that distinct light perception and signal
      transduction pathways regulate these two differential mechanisms for resistance,
      providing evidence for a coordinated regulation of the activity of the MVA
      pathway and the crosstalk between cell compartments for isoprenoid biosynthesis
      during the first stages of seedling development.

PMID- 14660802
TI  - Gamma-tubulin in basal land plants: characterization, localization, and
      implication in the evolution of acentriolar microtubule organizing centers.
AB  - Although seed plants have gamma-tubulin, a ubiquitous component of centrosomes
      associated with microtubule nucleation in algal and animal cells, they do not
      have discrete microtubule organizing centers (MTOCs) comparable to animal
      centrosomes, and the organization of microtubule arrays in plants has remained
      enigmatic. Spindle development in basal land plants has revealed a surprising
      variety of MTOCs that may represent milestones in the evolution of the typical
      diffuse acentrosomal plant spindle. We have isolated and characterized the gamma
      tubulin gene from a liverwort, one of the extant basal land plants. Sequence
      similarity to the gamma-tubulin gene of higher plants suggests that the gamma
      tubulin gene is highly conserved in land plants. The G9 antibody to fission yeast
      gamma-tubulin recognized a single band of 55 kD in immunoblots from bryophytes.
      Immunohistochemistry with the G9 antibody clearly documented the association of
      gamma-tubulin with various MTOC sites in basal land plants (e.g., discrete
      centrosomes with and without centrioles and the plastid surface in monoplastidic
      meiosis of bryophytes). Changes in the distribution of gamma-tubulin occur in a
      cell cycle-specific manner during monoplastidic meiosis in the liverwort
      Dumortiera hirsuta. gamma-Tubulin changes its localization from the plastid
      surface in prophase I to the spindle, from the spindle to phragmoplasts and the
      nuclear envelope in telophase I, and back to the plastid surfaces in prophase II.
      In vitro experiments show that gamma-tubulin is detectable on the surface of
      isolated plastids and nuclei of D. hirsuta, and microtubules can be repolymerized
      from the isolated plastids. gamma-Tubulin localization patterns on plastid and
      nuclear surfaces are not affected by the destruction of microtubules by oryzalin.
      We conclude that gamma-tubulin is a highly conserved protein associated with
      microtubule nucleation in basal land plants and that it has a cell cycle
      dependent distribution essential for the orderly succession of microtubule
      arrays.

PMID- 14660805
TI  - Suicide prevention and intervention: a call to all doctors.

PMID- 14660804
TI  - A plant caspase-like protease activated during the hypersensitive response.
AB  - To test the hypothesis that caspase-like proteases exist and are critically
      involved in the implementation of programmed cell death (PCD) in plants, a search
      was undertaken for plant caspases activated during the N gene-mediated
      hypersensitive response (HR; a form of pathogen-induced PCD in plants) in tobacco
      plants infected with Tobacco mosaic virus (TMV). For detection, characterization,
      and partial purification of a tobacco caspase, the Agrobacterium tumefaciens
      VirD2 protein, shown here to be cleaved specifically at two sites (TATD and GEQD)
      by human caspase-3, was used as a target. In tobacco leaves, specific proteolytic
      processing of the ectopically produced VirD2 derivatives at these sites was found
      to occur early in the course of the HR triggered by TMV. A proteolytic activity
      capable of specifically cleaving the model substrate at TATD was partially
      purified from these leaves. A tetrapeptide aldehyde designed and synthesized on
      the basis of the elucidated plant caspase cleavage site prevented fragmentation
      of the substrate protein by plant and human caspases in vitro and counteracted
      TMV-triggered HR in vivo. Therefore, our data provide a characterization of
      caspase-specific protein fragmentation in apoptotic plant cells, with
      implications for the importance of such activity in the implementation of plant
      PCD.

PMID- 14660803
TI  - A CDC45 homolog in Arabidopsis is essential for meiosis, as shown by RNA
      interference-induced gene silencing.
AB  - CDC45 is required for the initiation of DNA replication in yeast and cell
      proliferation in mammals and functions as a DNA polymerase alpha loading factor
      in Xenopus. We have cloned a CDC45 homolog from Arabidopsis whose expression is
      upregulated at the G1/S transition and in young meiotic flower buds. One-third of
      Arabidopsis 35S:CDC45 T1 RNA interference lines are partially to completely
      sterile, and the proportion of sterile plants is increased by using a dmc1
      promoter. T1 plants have decreased levels of the CDC45 transcript and contain 21-
      to 23-bp RNA fragments specific to the CDC45 gene. T2 transgenic lines, in which
      small RNA fragments are still present, were used to analyze S-phase entry by 5
      bromodeoxyuridine incorporation, which was not altered compared with that in the
      wild type. However, microarray data show that other cell cycle genes are
      upregulated or downregulated. T2 plants also have highly reduced fertility. The
      severity of the phenotype is correlated with the levels of the CDC45 transcript
      and small RNA fragments. Severe chromosome fragmentation arising during meiosis,
      which is not the result of a defect in the repair of SPO11-induced double strand
      breaks, leads to abnormal chromosome segregation and defective pollen and ovule
      development.

PMID- 14660806
TI  - Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a
      multicentre retrospective matched cohort study.
AB  - OBJECTIVES: To investigate the possible benefits and adverse effects of the
      addition of lopinavir/ritonavir to a standard treatment protocol for the
      treatment of severe acute respiratory syndrome. DESIGN: Retrospective matched
      cohort study. SETTING: Four acute regional hospitals in Hong Kong. PATIENTS AND
      METHODS: Seventy-five patients with severe acute respiratory syndrome treated
      with lopinavir/ritonavir in addition to a standard treatment protocol adopted by
      the Hospital Authority were matched with controls retrieved from the Hospital
      Authority severe acute respiratory syndrome central database. Matching was done
      with respect to age, sex, the presence of co-morbidities, lactate dehydrogenase
      level and the use of pulse steroid therapy. The 75 patients treated with
      lopinavir/ritonavir were divided into two subgroups for analysis:
      lopinavir/ritonavir as initial treatment, and lopinavir/ritonavir as rescue
      therapy. These groups were compared with matched cohorts of 634 and 343 patients,
      respectively. Outcomes including overall death rate, oxygen desaturation,
      intubation rate, and use of pulse methylprednisolone were reviewed. RESULTS: The
      addition of lopinavir/ritonavir as initial treatment was associated with a
      reduction in the overall death rate (2.3%) and intubation rate (0%), when
      compared with a matched cohort who received standard treatment (15.6% and 11.0%
      respectively, P<0.05) and a lower rate of use of methylprednisolone at a lower
      mean dose. The subgroup who had received lopinavir/ritonavir as rescue therapy,
      showed no difference in overall death rate and rates of oxygen desaturation and
      intubation compared with the matched cohort, and received a higher mean dose of
      methylprednisolone. CONCLUSION: The addition of lopinavir/ritonavir to a standard
      treatment protocol as an initial treatment for severe acute respiratory syndrome
      appeared to be associated with improved clinical outcome. A randomised double
      blind placebo-controlled trial is recommended during future epidemics to further
      evaluate this treatment.

PMID- 14660807
TI  - Status of obstetric epidural analgesia services in Hong Kong public hospitals:
      postal questionnaire survey.
AB  - OBJECTIVE: To examine the status of obstetric epidural analgesia services in Hong
      Kong public hospitals in 2001, and to compare findings with those from a similar
      survey conducted in 1995. DESIGN: Postal questionnaire survey. SETTING: Hospital
      Authority hospitals in Hong Kong offering an obstetric and delivery service.
      PARTICIPANTS: Chiefs of Service of departments of anaesthesia and coordinators of
      obstetric anaesthesia and analgesia service. MAIN OUTCOME MEASURES: The
      availability of an obstetric epidural analgesia service, specialist staff
      allocation to the service, existence of clinical protocols, rate of epidural
      analgesia, techniques of epidural administration, obstetric outcome or mode of
      delivery, and the incidence of adverse events associated with the use of epidural
      analgesia. RESULTS: Between 1 January and 31 December 2001, all eight Hospital
      Authority hospitals with an obstetric service provided epidural analgesia for
      labour pain relief, but only six (75%) offered a 24-hour service. A dedicated
      anaesthetist provided obstetric anaesthesia and analgesia during office hours in
      all units, but after hours in only three. This level of service provision
      compared favourably with that available in 1995, when only 82% of public
      maternity units provided epidural analgesia and only 36% offered a 24-hour
      service. The median epidural analgesia rate was 15% (range, 8%-20%) compared with
      10% in 1995. The incidence of adverse events and complications was very low.
      Formal written protocols for the conduct of epidural analgesia for labour were
      used in six units. All units used mixtures of local anaesthetic combined with
      opioid, administered as intermittent boluses, continuous epidural infusion, or
      patient-controlled epidural analgesia. CONCLUSIONS: Although there has been
      progress and improvement in the provision of obstetric epidural analgesia
      services in our public hospitals, the rate is still relatively low and the
      provision of services after hours is limited. Further progress will likely be
      hindered by current or future cutbacks in public hospital budgets.

PMID- 14660808
TI  - Penicillin and vancomycin tolerance among clinical isolates of Streptococcus
      pneumoniae in Hong Kong.
AB  - OBJECTIVE: To determine the prevalence of penicillin and vancomycin tolerance in
      clinical isolates of Streptococcus pneumoniae. DESIGN: Laboratory testing of 50
      consecutive clinical isolates. SETTING: District hospital, Hong Kong. PATIENTS:
      Fifty patients with pneumonia or meningitis who were admitted to a district
      hospital in Hong Kong between August and October 2002. MAIN OUTCOME MEASURES:
      Lysis, as assessed by loss of optical density at 4 hours at 540 nm, and reduction
      in viable count expressed as the log of the number killed ('log kill') after
      exposure of cultures to 10 times the minimum inhibitory concentration of
      penicillin and vancomycin. RESULTS: Of the 50 isolates, five (10%) were tolerant
      to penicillin and one (2%) was tolerant to vancomycin. CONCLUSION: This is the
      first report of vancomycin tolerance in Streptococcus pneumoniae in Hong Kong.
      Because vancomycin tolerance is associated with clinical failure in the treatment
      of pneumococcal meningitis, increased monitoring for resistant strains of
      organisms is suggested.

PMID- 14660809
TI  - Suicide in Hong Kong: epidemiological profile and burden analysis, 1981 to 2001.
AB  - OBJECTIVE: To describe changes of the epidemiological profile of suicides in Hong
      Kong, and the burden of suicides in terms of years of life lost between 1981 and
      2001. DESIGN: Retrospective study. SETTING: Hong Kong. PARTICIPANTS: Data on
      registered deaths of the Hong Kong population from 1981 to 2001 were retrieved
      from records of the Census and Statistics Department of the Government of the
      Hong Kong Special Administrative Region. MAIN OUTCOME MEASURES: Crude,
      standardised, age- and sex-standardised suicide rates; years of life lost;
      suicide method used; and rank among leading causes of death. RESULTS: Suicide
      ranked sixth in the leading cause of deaths and represented about 3% of all
      deaths each year. The suicide rate has increased from 9.6 per 100000 to 15 per
      100000 between 1981 and 2001. The total years of life lost due to suicide
      increased by 96.0%, from about 9900 years in 1981 to 19 400 years in 2001,
      whereas the figure for all causes of death decreased by 14.0%, from 274600 years
      to 236700 years. The total share of years of life lost attributable to suicide
      deaths has increased from 3.6% to 8.1% and is still increasing, especially among
      the middle age-groups (30-59 years). The use of charcoal burning as a suicide
      method has increased from 6.0% before 1998 to more than 28.0% in 2001.
      CONCLUSION: The burden on the years of life lost due to suicide is underestimated
      and overlooked. The increase of suicides in recent years has had a significant
      impact on the years of life lost and can be used as a useful indicator of
      performance in Hong Kong.

PMID- 14660810
TI  - Effect of adding a Chinese herbal preparation to acupuncture for seasonal
      allergic rhinitis: randomised double-blind controlled trial.
AB  - OBJECTIVE: To assess whether the addition of a Chinese herbal medicine formula to
      acupuncture affects the severity of symptoms and quality-of-life scores among
      patients with seasonal allergic rhinitis. DESIGN: Randomised double-blind placebo
      controlled trial. SETTING: University teaching and research clinic, Australia.
      PARTICIPANTS: Sixty-five patients with seasonal allergic rhinitis, who were
      recruited through public media. INTERVENTION: Between July and December 1999,
      patients received acupuncture twice a week for 8 weeks plus either a Chinese
      herbal drug formula (n=33) or placebo (n=32) at a dosage of four capsules, three
      times daily. MAIN OUTCOME MEASURES: The severity of nasal and non-nasal symptoms
      on a five-point scale, as assessed by both patients and an ear, nose, and throat
      specialist, and quality-of-life scores as measured by the Rhinoconjunctivitis and
      Rhinitis Quality of Life Questionnaire. RESULTS: Sixty-one patients completed the
      study (31 in the intervention group and 30 in the control group). After 8 weeks,
      no significant difference was found between the two groups in the severity of
      nasal and non-nasal symptoms and in the Rhinoconjunctivitis and Rhinitis Quality
      of Life Questionnaire scores. Intention-to-treat analysis of categorical
      variables showed moderate-to-marked improvement rates of 72.7% and 81.2% for
      intervention and control groups, respectively. Six patients reported mild adverse
      events-three from each of the study groups. CONCLUSION: The Chinese herbal
      formulation under investigation did not provide additional symptomatic relief or
      improvement in quality-of-life scores among patients with seasonal allergic
      rhinitis who were receiving acupuncture.

PMID- 14660811
TI  - Emergency aortic stent grafting for traumatic rupture of the thoracic aorta.
AB  - OBJECTIVE: To investigate the role of aortic stent grafting in emergency
      treatment of traumatic rupture of the descending thoracic aorta in patients with
      multiple injuries. DESIGN: Retrospective study. SETTING: Cardiothoracic surgery
      facility of a tertiary referral hospital, Hong Kong. PATIENTS: Between September
      2001 and September 2002, four patients who had sustained a blunt injury to the
      chest after high-speed deceleration injury were recruited. Three patients were
      treated with stent grafting because concomitant head injury and multiple other
      injuries precluded the use of open thoracic surgery. One patient had no head
      injury and was offered stent grafting as a less invasive treatment. INTERVENTION:
      The pseudoaneurysm was covered with an aortic stent graft under fluoroscopic and
      angiographic guidance. MAIN OUTCOME MEASURES: Technical success of treatment,
      complications, and treatment outcome. RESULTS: Three patients recovered and were
      discharged from hospital. The computed tomography scan at 3 months to 6 months
      after surgery showed resolution of the pseudoaneurysm. The final patient was
      still in the hospital. Follow-up computed tomography 2 weeks later showed
      exclusion of the pseudoaneurysm. There was one external iliac artery thrombosis
      on the side of femoral arteriotomy, which was recanalised with thrombectomy.
      There was another unintentional partial coverage of the left subclavian artery,
      which was asymptomatic. No other major complication was present and there was no
      paraplegia after the stent grafting. CONCLUSION: Aortic stent graft is useful for
      emergency treatment of descending thoracic aortic injury. In the short term, it
      causes less morbidity and mortality than does open surgery, and can be life
      saving when there is no surgical alternative. The long-term effect is still
      unknown.

PMID- 14660812
TI  - Consensus statement on iodine deficiency disorders in Hong Kong.
AB  - This article reviews the available data on the study of iodine deficiency
      disorders in Hong Kong and to discuss the approach towards preventing such
      disorders in Hong Kong. The importance of iodine and iodine deficiency disorders
      is described, and the available data on the dietary iodine intake and urinary
      iodine concentration in different populations of Hong Kong are summarised and
      discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is
      associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal
      hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in
      Hong Kong. Women of reproductive age, and pregnant and lactating women should be
      made aware and educated to have an adequate iodine intake, such as iodised salt,
      as an interim measure. A steering group involving all stakeholders should be
      formed to advise on the strategy of ensuring adequate iodine intake, including
      universal iodisation of salt in Hong Kong. Continuous surveillance of iodine
      status in the Hong Kong population is necessary.

PMID- 14660813
TI  - A case of oral myiasis due to Chrysomya bezziana.
AB  - Chrysomya bezziana is a causative agent of obligatory myiasis. We report the
      first case of human infestation of Chrysomya bezziana in Hong Kong in an 89-year
      old woman who had previously had a stroke. One day after hospital admission for
      fever, a small fissure at the labial gingiva of the upper incisors and several
      ulcerative lesions at the hard palate were noticed during routine mouth care. A
      live maggot was seen protruding from the small fissure. In the following few
      days, a total of seven maggots were removed by forceps. Urgent computed
      tomography and magnetic resonance imaging of the oral cavity showed an ulcerative
      soft-tissue lesion over the anterior palate, with a fistula communicating to the
      labial gingiva. The tissue loss was limited to the bony margin of the hard
      palate. The infestation was managed by manual removal of maggots and surgical
      debridement. Medical personnel taking care of old or debilitated patients need to
      bear in mind the possibility of Chrysomya bezziana infestation to be able to make
      a prompt diagnosis and implement relevant intervention to prevent extensive
      tissue destruction.

PMID- 14660814
TI  - Rare pulmonary complications after transarterial chemoembolisation for
      hepatocellular carcinoma: two case reports.
AB  - We report two rare cases of acute pulmonary complication after transarterial
      chemoembolisation for inoperable hepatocellular carcinoma. Both cases involved a
      large tumour and hepatic vein invasion. The first patient, a 27-year-old man,
      died of pulmonary tumour embolism 4 days after transarterial chemoembolisation.
      Acute dyspnoea developed in the second patient, a 63-year-old man, following the
      procedure due to pulmonary oil embolisation and chemical pneumonitis. The chest
      condition of this patient improved, but he subsequently died of liver failure 3
      weeks later. Our cases illustrate the point that if locoregional treatment is
      offered as a palliative treatment, patients with hepatic vein invasion should be
      warned of the possible complications of massive tumour embolism, pulmonary oil
      embolisation, and subsequent death.

PMID- 14660815
TI  - Small bowel perforation after radiotherapy for cervical carcinoma.
AB  - Radiotherapy is the treatment of choice for carcinoma of the uterine cervix. We
      report on a 62-year-old Chinese woman with cervical carcinoma, in whom a small
      bowel perforation developed 5 months after radiotherapy. Ten centimetres of small
      bowel, including the perforation site, were resected. No bowel adhesion was
      detected during the operation. The postoperative course was uneventful, and the
      patient was discharged home 7 days after surgery. Histological examination
      confirmed post-irradiation injury. The presenting complaints of patients with
      bowel perforation following radiotherapy vary, and signs of peritonitis may be
      absent. Emergency physicians must be alert for these complications in patients
      who have been treated with radiotherapy.

PMID- 14660816
TI  - A Chinese family with familial dysalbuminaemic hyperthyroxinaemia.
AB  - We report the results of biochemical and genetic studies in a Chinese family with
      familial dysalbuminaemic hyperthyroxinaemia. Total thyroxine levels were 1.2 to
      1.7 times the upper limit of the reference range and free thyroxine levels were
      1.2 to 1.6 times the upper reference limit. Concentrations of thyroid-stimulating
      hormone (thyrotropin) and free tri-iodothyronine were normal in all family
      members tested. Overall, thyroid function tests showed high total thyroxine
      levels in five males and two females over two generations in the family. The
      diagnosis of familial dysalbuminaemic hyperthyroxinaemia was confirmed by the
      detection of a guanine to adenine missense mutation in the second nucleotide of
      codon 218 of the gene encoding human serum albumin, showing that the mutation in
      this family is the same as that previously found in Caucasian populations.

PMID- 14660817
TI  - Advent of recombinant human growth hormone to increase final adult height of the
      normal child.

PMID- 14660818
TI  - The health of female sex workers in Hong Kong: do we care?

PMID- 14660819
TI  - Vascular endothelial growth factor (VEGF)-eluting stents: in vivo effects on
      thrombosis, endothelialization and intimal hyperplasia.
AB  - Local drug delivery by stent can reduce in-stent restenosis. Vascular endothelial
      growth factor (VEGF) is an endothelial cell-specific mitogen. After stenting, the
      arterial wall is almost denuded of endothelium. This loss of endothelium
      contributes to the smooth muscle cell (SMC) proliferation seen in restenosis,
      since the endothelium actively inhibits SMC hyperplasia. Over time, the
      endothelium recovers and SMC hyperplasia is arrested. The capacity of VEGF-coated
      stents to accelerate re-endothelialization, and to therefore reduce restenosis
      and thrombosis, was tested in this study. Radiolabeled VEGF was absorbed onto
      stents and released over nine days in an in vitro perfusion circuit. VEGF-coated
      stents were deployed in arterial segments to study local tissue release. A New
      Zealand White rabbit iliac artery model for stent implantation was used. Re
      endothelialization and thrombosis were assessed after seven days. Further animals
      were examined 28 days post-procedure for in-stent restenosis. Stented vessels
      were resin-embedded, sectioned and stained. Intimal thickening was calculated
      using computerized morphometry. In vitro, the stents released 80% of the initial
      load over nine days. At seven days, thrombus was significantly reduced (12.5 mg
      for controls versus 0 mg for VEGF; p = 0.014). No beneficial effect was seen on
      endothelialization, nor on intimal hyperplasia. Neointimal area was 2.2   0.9 mm2
      for controls versus 2.4   1.8 mm2 for VEGF (p = 0.8). These VEGF-eluting stents
      do not accelerate re-endothelialization or inhibit restenosis. Stent thrombosis
      appears to be reduced, which may make these stents less thrombogenic and be
      valuable in higher-risk cases.

PMID- 14660820
TI  - Improved efficiency in acute myocardial infarction care through commitment to
      emergency department-initiated primary PCI.
AB  - STUDY OBJECTIVE: Demonstrate improved efficiency of initial and subsequent in
      hospital care following emergency department (ED) physician-initiated primary
      angioplasty (1 PCI). METHODS: An observational study was undertaken in ST
      elevation myocardial infarction patients presenting to a community hospital
      emergency department. Outcomes of patients who received ED physician-directed 1
      PCI were compared with patients previously treated by a mix of ED physician and
      cardiologist co-determined thrombolysis or 1 PCI. A process improvement
      initiative supported the change to ED-directed 1 PCI. RESULTS: The study included
      287 eligible acute reperfusion patients. Median door-to-balloon time (MDBT)
      improved from 88 minutes (95% CI, 80 96) to 61 minutes (95% CI, 57 70; p <
      0.0001). Necessary subsequent in-hospital interventions (NSI) occurred in 70 of
      107 (65.4%; 95% CI, 55.6 74.4%) thrombolytic patients, versus 3 of 99 (3.0%; 95%
      CI, 0.6 8.6%) 1 PCI patients at baseline, and 1 of 81 (1.2%; 95% CI, 0.0 6.7%) 1
      PCI patients after process change. Median length of stay (LOS) decreased from 4
      days for thrombolytic patients and 3 days for 1 PCI patients at baseline, to 2
      days for 1 PCI after adopting the improved process (p < 0.0001). Effectiveness
      outcomes demonstrating improvement included discharge on beta-blocker (p =
      0.0039), angiotensin-converting-enzyme inhibitor (p < 0.0001) and anti-lipid
      therapy (p = 0.0039), with favorable trends in survival to discharge, and 30-day
      major adverse cardiac events (MACE). CONCLUSIONS: Conversion to ED physician
      initiated 1 PCI for ST-elevation myocardial infarction significantly improved
      efficiency of care as measured by MDBT, NSI and LOS. Effectiveness measures,
      including survival to discharge, discharge medications and 30-day MACE,
      demonstrated improvement or favorable trends.

PMID- 14660821
TI  - Optimal timing of hydration to erase contrast-associated nephropathy: the OTHER
      CAN study.
AB  - Intravascular contrast agents remain a common cause of acute renal dysfunction,
      and prolonged intravenous saline administration prior to contrast exposure has
      been recommended in patients with elevated creatinine levels. For patient
      convenience and to minimize cost, same-day procedures have become common in
      patients with moderate renal insufficiency, despite little evidence to support
      this practice. A randomized trial was therefore performed to compare overnight
      hydration with bolus hydration in patients with moderate renal insufficiency.
      Although no overall change in creatinine was seen at 24 or 48 hours, four of the
      37 patients (10.8%) in the bolus group versus none of the 26 in the overnight
      hydration group developed contrast associated nephropathy (CAN; p = 0.136). These
      results should at least question whether bolus hydration should be considered an
      equivalent alternative to overnight hydration in patients at risk for CAN
      undergoing angiography, and encourage further evaluation of this issue.

PMID- 14660822
TI  - Water for contrast-induced nephropathy? A thirst for knowledge.

PMID- 14660823
TI  - Clinical outcome following combination of cutting balloon angioplasty and
      coronary beta-radiation for in-stent restenosis: a report from the RENO registry.
AB  - At present, vascular brachytherapy is the only efficient therapy for in-stent
      restenosis. Nevertheless, edge restenosis often related to geographical miss has
      been identified as a major limitation of the technique. The non-slippery cutting
      balloon has the potential to limit vascular barotraumas, which, together with low
      dose irradiation at both ends of the radioactive source, are the prerequisite for
      geographical miss. This prospective study aimed to examine the efficacy of
      combining cutting balloon angioplasty and brachytherapy for in-stent restenosis.
      The Radiation in Europe NOvoste (RENO) registry prospectively tracked all
      patients who had been treated by coronary beta-radiation with the Beta-Cath
      System (Novoste Corporation, Brussels, Belgium) but were not included in a
      randomized radiation trial. A subgroup of patients with in-stent restenosis
      treated by cutting balloon angioplasty and coronary beta-radiation (group 1, n =
      166) was prospectively defined, and clinical outcomes of patients at 6 months
      were compared with those of patients treated by conventional angioplasty and
      coronary beta-radiation (group 2, n = 712). At 6-month follow-up, there was a
      significant difference between groups 1 and 2 in target vessel revascularization
      (10.2% versus 16.6% respectively; p = 0.04) and in the incidence of major adverse
      clinical events (MACE) including death, myocardial infarction, and
      revascularization (10.8% versus 19.2%; p = 0.01). This observation was confirmed
      by a multivariate analysis indicating a lower risk for MACE at 6 months (odds
      ratio: 0.49; confidence intervals: 0.27 0.88; p = 0.02). Compared to conventional
      angioplasty, cutting balloon angioplasty prior to coronary beta-radiation with
      the Beta-Cath System seems to improve the 6-month clinical outcome in patients
      with in-stent restenosis.

PMID- 14660824
TI  - To cut is to cure?

PMID- 14660825
TI  - Improving in-hospital mortality in the setting of an increasing risk profile
      among patients undergoing catheter-based reperfusion for an acute myocardial
      infarction without cardiogenic shock.
AB  - Prompt myocardial reperfusion is the therapeutic goal for patients presenting
      with acute myocardial infarction (AMI). However, there remains a paucity of
      clinical data from single centers solely dedicated to a catheter-based
      reperfusion strategy. Therefore, we sought to identify significant predictors of
      in-hospital mortality, to determine the changing profile of patient demographics
      and to identify the mortality trend over time. METHODS: Consecutive patients who
      underwent percutaneous coronary intervention (PCI) for an AMI between January of
      1982 and December of 1999 were included in this multivariable analysis (excluding
      cardiogenic shock). AMI was defined as an evolving myocardial infarction within
      the preceding 24 hours. The primary endpoint for this analysis was in-hospital
      mortality. RESULTS: There were 2,745 patients identified in this study, of which
      8.3% (n = 228) were non-survivors. The significant multivariable predictors of in
      hospital mortality included creatinine > 1.5 mg/dl [relative risk (RR), 5.7; 95%
      confidence interval (CI) 4.0 8.1], ejection fraction < 40% (RR, 6.6; 95% CI, 4.3
      10.0), multivessel disease (RR, 2.8; 95% CI, 1.9 4.2), female (RR, 2.3; 95% CI,
      1.6 3.1) and age > 70 years (RR, 1.6; 95% CI, 1.1 2.2). The incidence of patients
      with these high-risk characteristics increased in recent years; thus, the
      unadjusted slope of the mortality trend over 20 years was not significant.
      However, following adjustment for the temporal shift in high-risk variables,
      there was a significant reduction in the adjusted in-hospital mortality rate (RR,
      0.89; 95% CI 0.8 0.98; p = 0.017). Despite the changing risk profile, the short
      term mortality continues to improve for patients undergoing AMI PCI.

PMID- 14660826
TI  - An unusual complication of coil embolization of a large coronary-pulmonary
      fistula.
AB  - A 58-year-old man with hemoptysis was found to have a large fistula from his
      circumflex artery to the pulmonary system. Coil embolization was performed. This
      resulted in occlusion of the fistula, including a small branch likely supplying
      the sinus node. Following the procedure he developed junctional bradycardia but
      remained hemodynamically stable. He had a brief period of atrial fibrillation
      which, after 48 hours, reverted to a rhythm from an ectopic focus in the low
      right atrium. This case highlights an unusual complication of fistula
      embolization and emphasizes the need for caution when occluding vessels which may
      supply the sinus node.

PMID- 14660827
TI  - Stent fracture after stent therapy for aortic coarctation.

PMID- 14660828
TI  - Occlusion of the saphenous vein graft at the site of polytetrafluoroethylene
      membrane-covered stent implantation: was it late thrombosis?

PMID- 14660829
TI  - Percutaneous coronary intervention for myocardial infarction during pregnancy: a
      new trend?
AB  - Recent studies report that American women are increasingly delaying their first
      births. While the proportion of births in older women has been increasing, there
      is also increased prevalence of cardiovascular risk factors and complications of
      pregnancy with increasing maternal age. We present 2 cases of acute myocardial
      infarction occurring during pregnancy. The mothers were both over 35 years old,
      and had significant risk factors for coronary disease. Both were found to have
      atherosclerotic coronary lesions, and were managed with coronary intervention
      with successful reperfusion. One woman successfully delivered a healthy infant at
      term. The other had a spontaneous abortion shortly after discharge from the
      hospital. Given current demographic trends, it is likely that such cases will be
      more commonly seen.

PMID- 14660830
TI  - Coronary artery-left ventricle fistula after PTCA: diagnosed by contrast
      echocardiography.
AB  - A coronary artery fistula is a rare complication following percutaneous
      transluminal coronary angioplasty (PTCA). It may result in communication with
      either the left or right ventricle. Previous reported cases were diagnosed by
      coronary angiography using contrast medium. We present a case with a septal
      coronary artery fistula to the left ventricle following PTCA that was diagnosed
      by contrast echocardiography.

PMID- 14660831
TI  - Repeat radiation for recurrent in-stent restenosis in patients who failed initial
      brachytherapy.
AB  - In-stent restenosis (ISR) is due to neointimal hyperplasia and is shown to be
      effectively inhibited by vascular brachytherapy (VBT). Despite its efficacy, 20
      25% of patients present with recurrent ISR following failed initial VBT. Although
      conventional percutaneous coronary intervention (PCI) is offered in a majority of
      patients to treat failed brachytherapy, the requirement for repeat
      revascularization is about 50%. PCI with repeat radiation to treat this difficult
      subset of patients is safe and feasible with target lesion revascularization
      (TLR) rates less than 25%. The lessons learned from randomized trials of
      brachytherapy, including prevention of edge effect, prolonged antiplatelet
      therapy and the prescription of a higher mean dose, should be applied to treat
      these patients with repeat radiation.

PMID- 14660832
TI  - Right atrial thrombus attached to an indwelling central venous catheter.

PMID- 14660833
TI  - Use of vaccines for the prevention of typhoid fever.

PMID- 14660835
TI  - Longitudinal growth patterns of Pakistani infants in a clinic based growth
      promotion program.
AB  - OBJECTIVE: To describe the operation of growth monitoring and promotion (GMP)
      clinic and longitudinal growth patterns of children. DESIGN: Prospective
      observation and intervention. SETTING: Outpatient department of a teaching
      hospital. METHODS: Less than 6 months old infants were registered at GMP clinic
      and followed for up to two years of age. Mothers were provided information,
      education and counselling about healthy growth of their infants. The outcome
      measure was change in weight after follow-up. RESULTS: We enrolled a cohort of
      553 children in the first 6 months of life, of which 318 were males. Mean follow
      up period was 15.7 (SD+/-6.4) months. At enrollment 207 were underweight [weight
      for-age Z score (WAZ<-2], of which 153 were from low-income families. The
      children from poorer families also gained weight regularly, although it was less
      than the higher income families. Of 346 infants with normal weight at
      registration, 305 maintained their weight gain by last follow-up visit. Of 207
      underweight infants at enrollment 128 improved their weight gain by the last
      follow-up visit. Overall 433 infants followed-up at our GMP clinic either
      maintained or improved their weight gain. CONCLUSIONS: Children at risk of
      undernutrition should be identified at an early age and through effective
      interaction between health workers and the family, their growth can be improved.
      Children of poor families can also benefit from this activity, provided a
      comprehensive approach is made available.

PMID- 14660834
TI  - Chronic renal failure in children.
AB  - OBJECTIVE: To determine the etiology of chronic renal failure amongst children
      attending the Pediatric Nephrology services at a tertiary care center. SUBJECT:
      We reviewed the records of 305 children, diagnosed to have chronic renal failure
      (CRF) over a 7-year period. CRF was defined as glomerular filtration rate (GFR)
      below 50-mL/1.73 m2/min persisting for more than 3 months. RESULTS: The mean age
      at onset and presentation of CRF in these patients was 5.9 and 8 years
      respectively. Ninety-six children were below 5 years of age. Mean (SD) levels of
      blood urea and creatinine at presentation were 150 and 4.6 mg/dL respectively.
      The median GFR at presentation was 18.5 mL/min/1.73 m(2) while 25.3 patients were
      already in end stage renal failure indicating that these patients were referred
      late. The mean (SD) hemoglobin at presentation was 7.6 (2.6) g/dL. The mean
      height and weight SD scores were 2.9 and 2.4 respectively. Obstructive uropathy
      was the commonest cause of CRF present in 97 children. Other causes included
      chronic glomerulonephritis in 84, reflux nephropathy in 51, hereditary nephritis
      in 20, renal dysplasia in 15 and hemolytic uremic syndrome in 5 children. The
      mean (SD) duration of follow-up was 11(15) months. Peritoneal or hemodialysis was
      performed in 63 patients. Fifteen patients underwent a live-related renal
      transplantation. The rest opted out of dialysis program and were conservatively
      managed due to financial constraints. CONCLUSIONS: The commonest causes of CRF
      were obstructive and reflux nephropathy. A significant proportion of patients
      presented late; had severe CRF and were malnourished and stunted. Majority of
      these were managed conservatively due to lack of financial resources.

PMID- 14660836
TI  - Nutritional management of children with cystic fibrosis.

PMID- 14660837
TI  - Neurobehavioral assessment of appropriate for gestational and small for
      gestational age babies.
AB  - he present study was conducted to evaluate the neurobehaviour of term appropriate
      for gestational aland small for gestational age babies during the first two weeks
      of life in a tertiary care hospital. Forty eight appropriate and thirty small for
      gestation age babies were evaluated using Brazelton Neurobehavioural Assessment
      Scale on 3rd, 7th and 14th day of life. The behaviour of AGA babies is
      characterized by optimal performance in habituation, range of state, regulation
      of state and autonomic stability. The behavior is at low to mid-range in
      orientation and in motor clusters. All the behavior clusters showed improvement
      over first 14 days except for regulation of state which showed a lower
      performance on day 7 and 14. The behavior performance of SGA babies on day 3,
      compared to AGA babies, was lower in all the clusters except orientation where
      they performed much better. The percentage improvement of scores in SGA babies is
      higher than in AGA babies and by day 14 SGA babies are scoring higher than AGA
      babies in orientation, autonomic stability and regulation of state. The
      difference in the neurobehavior pattern of babies in relation to their
      intrauterine growth suggests need for appropriate care.

PMID- 14660838
TI  - Anti-streptolysin O titers in normal healthy children of 5-15 years.
AB  - Antistreptolysin O (ASO) levels vary with age group of the study population and
      geographical locations. The present study was undertaken to determine the upper
      limit of normal of ASO in 200 normal children of 5-15 years of age with no
      history of recent sore throat infection. The standard tube dilution method (WHO)
      was used for estimating ASO titers. It was found that 239 IU was the upper limit
      of normal in the study population, which can be considered as the baseline ASO
      titer. This can provide useful guidelines for physicians in the interpretation of
      elevated ASO titers in cases of suspected acute rheumatic fever.

PMID- 14660839
TI  - Clinical profile of severe scorpion envenomation in children at rural setting.
AB  - he present study is an attempt to evaluate the clinical manifestations of severe
      scorpion sting in children and their management at a rural setting. Twelve
      patients with severe scorpion sting referred from primary health center are
      presented in this report. Eight children had pulmonary edema and hypotension; two
      had pulmonary edema and hypertension while one each presented with hypertension
      and tachycardia in isolation. Oral prazosin, dobutamine infusion and sodium
      nitroprusside drip (SNP) were used as therapeutic options based on the
      symptomatology. Two children died of massive pulmonary edema despite use of SNP
      and dopamine drip. Anti scorpion venom did not prevent the cardiovascular
      manifestations of severe scorpion sting. Early administration of prazosin
      alleviated the severity of scorpion envenomation

PMID- 14660840
TI  - Gamma-sarcoglycanopathy.
AB  - The best known muscular dystrophies are X-linked dystrophinopathies. A clinically
      and genetically heterogeneous group presenting with weakness of the pelvic and
      shoulder girdles is that of the limb-girdle muscular dystrophies (LGMDs).
      Sarcoglycanopathies (SGPs) are autosomal recessive LGMDs. We report a rare case
      of primary gamma-sarcoglycanopathy (SGP) which emphasizes the evolving concept of
      dystrophinopathy to sarco-glycanopathy.

PMID- 14660841
TI  - Leptospirosis in children.
AB  - Leptospirosis has a broad spectrum of clinical manifestations varying, from
      inapparent influenza like illness to fulminant fatal disease with hepato-renal
      dysfunction and hemorrhagic phenomena. Our cases had fever, puffiness,
      respiratory distress and bleeding diathesis as leading manifestations.
      Leptospirosis was suspected in view of epidemic situation prevailing in the city.
      We report four cases here, three of which survived and one died.

PMID- 14660842
TI  - Congenital hypomyelinating neuropathy.
AB  - An eleven-month-old baby born out of non-consanguineous parentage presented with
      history of delayed motor milestones. The weakness was predominantly distal; there
      was intercostal muscle weakness, generalized hypotonia and areflexia. The nerve
      conduction velocities were unobtainable in all the four limbs. Sural nerve biopsy
      was consistent with the diagnosis of congenital hypomyelinating neuropathy, a
      rare form of hereditary motosensory neuropathy.

PMID- 14660843
TI  - Thoracoscopic repair of eventration of diaphragm.
AB  - pen thoracotomy and plication of eventration of diaphragm leads to
      hypoventilation due to pain and lung contusion due to retraction. We present two
      cases, 8 month and 4 years old; in whom plication was done thoracoscopically.
      Both had smooth recovery, early extubation and excellent cosmetic result.

PMID- 14660844
TI  - Subcutaneous emphysema.

PMID- 14660845
TI  - Doxorubicin induced melanonychia.

PMID- 14660846
TI  - Parathyroid adenoma in a two month old child.

PMID- 14660847
TI  - Neonatal oil massage.

PMID- 14660848
TI  - Polio eradication in India.

PMID- 14660849
TI  - Polio eradication in India.

PMID- 14660850
TI  - Polio eradication: future strategies.

PMID- 14660852
TI  - Anhidrotic ectodermal dysplasia presenting as atrophic rhinitis and maggots.

PMID- 14660853
TI  - Kawasaki disease with coronary artery aneurysm and symptomatic pneumonia.

PMID- 14660854
TI  - Homolateral linear morphea with coarctation of aorta.

PMID- 14660855
TI  - Jejunal web with late presentation.

PMID- 14660856
TI  - Inappropriate prescription of corticosteroids in respiratory infections.

PMID- 14660857
TI  - Adolescent pharmacology.

PMID- 14660858
TI  - The IMS Act 1992.

PMID- 14660859
TI  - Teaching aid: mock doll injection model.

PMID- 14660861
TI  - Bone marrow stromal cells and multi-lineage differentiation.

PMID- 14660860
TI  - Het up mould unleashes a sporekiller prion.

PMID- 14660862
TI  - Global warming and terrestrial carbon sequestration.

PMID- 14660865
TI  - After DNA at the MRC.

PMID- 14660866
TI  - The conservation of redundancy in genetic systems: effects of sexual and asexual
      reproduction.
AB  - The relationship between probability of survival and the number of deleterious
      mutations in the genome is investigated using three different models of highly
      redundant systems that interact with a threatening environment. Model one is a
      system that counters a potentially lethal infection; it has multiple identical
      components that act in sequence and in parallel. Model two has many different
      overlapping components that provide threefold coverage of a large number of vital
      functions. The third model is based on statistical decision theory: an ideal
      detector, following an optimum decision strategy, makes crucial decisions in an
      uncertain world. The probability of a fatal error is reduced by a redundant
      sampling system, but the chance of error rises as the system is impaired by
      deleterious mutations. In all three cases the survival profile shows a
      synergistic pattern in that the probability of survival falls slowly and then
      more rapidly. This is different than the multiplicative or independent survival
      profile that is often used in mathematical models. It is suggested that a
      synergistic profile is a property of redundant systems. Model one is then used to
      study the conservation of redundancy during sexual and asexual reproduction. A
      unicellular haploid organism reproducing asexually retains redundancy when the
      mutation rate is very low (0.001 per cell division), but tends to lose high
      levels of redundancy if the mutation rate is increased (0.01 to 0.1 per cell
      division). If a similar unicellular haploid organism has a sexual phase then
      redundancy is retained for mutation rates between 0.001 and 0.1 per cell
      division. The sexual organism outgrows the asexual organism when the above
      mutation rates apply. If they compete for finite resources the asexual organism
      will be extinguished. Variants of the sexual organism with increased redundancy
      will outgrow those with lower levels of redundancy and the sexual process
      facilitates the evolution of more complex forms. There is a limit to the extent
      that complexity can be increased by increasing the size of the genome and in
      asexual organisms this leads to progressive accumulation of mutations with loss
      of redundancy and eventual extinction. If complexity is increased by using genes
      in new combinations, the asexual form can reach a stable equilibrium, although it
      is associated with some loss of redundancy. The sexual form, by comparison, can
      survive, with retention of redundancy, even if the mutation rate is above one per
      generation. The conservation and evolution of redundancy, which is essential for
      complexity, depends on the sexual process of reproduction.

PMID- 14660867
TI  - Protein evolution: intrinsic preferences in peptide bond formation: a
      computational and experimental analysis.
AB  - Two possibilities exist for the evolution of individual enzymes/proteins from a
      milieu of amino acids, one based on preference and selectivity and the other on
      the basis of random events. Logic is overwhelmingly in favour of the former. By
      protein data base analysis and experiments, we have provided data to show the
      manifestation of two types of preferences, namely, the choice of the neighbour
      and its acceptance from the amino end (left) or the carboxyl end (right). The
      study tends to show that if the 20 proteinous amino acids were made to combine in
      water, the resulting profile would be nonrandom. Such selectivity could be a
      factor in protein evolution.

PMID- 14660868
TI  - The expression of GFP under the control of fibroin promotor in primary ovarian
      cells of Antheraea pernyi.
AB  - The fibroin promoter can stably express foreign gene in lepidopteran cells. Total
      RNA was extracted from the gland of silkworm, Antheraea pernyi and the
      transcription initiation site of fibroin gene of A. pernyi was identified by RNA
      ligase mediated rapid amplification of cDNA ends (RLM-RACE). The expression
      vector (pGFP-N2/Fib) was constructed by use of replacing the CMV promoter with
      the fibroin promoter. The results of visual screening under a fluorescent
      inverted microscope and Western blot analysis indicated that the GFP gene was
      expressed in the primary cells of ovary origins from A. pernyi.

PMID- 14660869
TI  - Calcium regulates the expression of a Dictyostelium discoideum asparaginyl tRNA
      synthetase gene.
AB  - In a screen for calcium-regulated gene expression during growth and development
      of Dictyostelium discoideum we have identified an asparaginyl tRNA synthetase
      (ddAsnRS) gene, the second tRNA synthetase gene identified in this organism. The
      ddAsnRS gene shows many unique features. One, it is repressed by lowering
      cellular calcium, making it the first known calcium-regulated tRNA synthetase.
      Two, despite the calcium-dependence, its expression is unaltered during the cell
      cycle, making this the first D. discoideum gene to show a calcium-dependent but
      cell cycle phase-independent expression. Finally, the N-terminal domain of the
      predicted ddAsnRS protein shows higher sequence similarity to Glutaminyl tRNA
      synthetases than to other Asn tRNA synthetases. These unique features of the
      AsnRS from this primitive eukaryote not only point to a novel mechanism
      regulating the components of translation machinery and gene expression by
      calcium, but also hint at a link between the evolution of GlnRS and AsnRS in
      eukaryotes.

PMID- 14660870
TI  - Effect of pH, temperature and alcohols on the stability of glycosylated and
      deglycosylated stem bromelain.
AB  - The biological significance of the carbohydrate moiety of a glycoprotein has been
      a matter of much speculation. In the present work, we have chosen stem bromelain
      from Ananas comosus as a model to investigate the role of glycosylation of
      proteins. Stem bromelain is a thiol protease which contains a single hetero
      oligosaccharide unit per molecule. Here, the deglycosylated form of the enzyme
      was obtained by periodate oxidation. The differences in the glycosylated and
      deglycosylated forms of the glycoprotein have been studied at various
      temperatures and pH values, using probes such as loss of enzyme activity and by
      the changes in fluorescence and circular dichroism spectra. Deglycosylated
      bromelain showed decreased enzyme activity and perturbed fluorescence and
      circular dichroism spectra. In addition to this, a comparative study of their
      activities in different organic solvents showed a marked decrease in case of
      deglycosylated form of the enzyme. It is thus concluded that glycosylation
      contributes towards the functional stability of glycoenzymes.

PMID- 14660872
TI  - Reconfirmation of antimicrobial activity in the coelomic fluid of the earthworm
      Eisenia fetida andrei by colorimetric assay.
AB  - A novel tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)
      2-(4-sulphophenyl)-2H-tetrazolium (MTS) was used in the assessment of
      antimicrobial activity in earthworm in the presence of phenazine methosulphate
      (PMS) as an electron coupling reagent. This activity was purified from the
      coelomic fluid of the earthworm (ECF), Eisenia fetida andrei (Oligochaeta,
      Lumbricidae, annelids) using a series of column chromatography techniques and was
      tested against three Gram-negative strains of Escherichia coli, Pseudomonas
      aeruginosa, Aeromonas hydrophila and three Gram-positive strains of
      Staphylococcus aureus, Bacillus megaterium, Arthrobacter sp., respectively. Only
      the pigment-free eluate of coelomic fluid of the earthworm (ECFPE) showed
      activity against B. megaterium amongst three isolated active fractions. The anion
      (DEAE-52) exchange effluent of the ECFPE was reported to have the strongest
      activity against P. aeruginosa amongst the three active fractions. The 20%
      acetonitrile eluate (AE) by Sep-Pak C18 cartridge was also tested and showed fair
      resistance against E. coli, P. aeruginosa and Arthrobacter sp., respectively.

PMID- 14660871
TI  - Curcumin-induced inhibition of cellular reactive oxygen species generation: novel
      therapeutic implications.
AB  - There is evidence for increased levels of circulating reactive oxygen species
      (ROS) in diabetics, as indirectly inferred by the findings of increased lipid
      peroxidation and decreased antioxidant status. Direct measurements of
      intracellular generation of ROS using fluorescent dyes also demonstrate an
      association of oxidative stress with diabetes. Although phenolic compounds
      attenuate oxidative stress-related tissue damage, there are concerns over
      toxicity of synthetic phenolic antioxidants and this has considerably stimulated
      interest in investigating the role of natural phenolics in medicinal
      applications. Curcumin (the primary active principle in turmeric, Curcuma longa
      Linn.) has been claimed to represent a potential antioxidant and antiinflammatory
      agent with phytonutrient and bioprotective properties. However there are lack of
      molecular studies to demonstrate its cellular action and potential molecular
      targets. In this study the antioxidant effect of curcumin as a function of
      changes in cellular ROS generation was tested. Our results clearly demonstrate
      that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and
      thapsigargin-induced ROS generation in cells from control and diabetic subjects.
      The pattern of these ROS inhibitory effects as a function of dose-dependency
      suggests that curcumin mechanistically interferes with protein kinase C (PKC) and
      calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that
      a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We
      suggest that the antioxidant and antiangeogenic actions of curcumin, as a
      mechanism of inhibition of Ca2+ entry and PKC activity, should be further
      exploited to develop suitable and novel drugs for the treatment of diabetic
      retinopathy and other diabetic complications.

PMID- 14660873
TI  - Role of ureogenesis in tackling problems of ammonia toxicity during exposure to
      higher ambient ammonia in the air-breathing walking catfish Clarias batrachus.
AB  - In the present study, the possible role of ureogenesis to avoid the accumulation
      of toxic ammonia to a lethal level under hyper-ammonia stress was tested in the
      air-breathing walking catfish Clarias batrachus by exposing the fish at 25 mM
      NH4Cl for 7 days. Excretion of ammonia by the NH4Cl-exposed fish was totally
      suppressed, which was accompanied by significant accumulation of ammonia in
      different body tissues. The walking catfish, which is otherwise predominantly
      ammoniotelic, turned totally towards ureotelism from ammoniotelism with a 5- to 6
      fold increase of urea-N excretion during exposure to higher ambient ammonia.
      Stimulation of ureogenesis was accompanied with significant increase of some of
      the key urea cycle enzymes such as carbamyl phosphate synthetase (urea cycle
      related), argininosuccinate synthetase and argininosuccinate lyase both in
      hepatic and non-hepatic tissues. Due to this unique physiological strategy of
      turning towards ureotelism from ammoniotelism via the induced urea cycle, this
      air-breathing catfish is able to survive in very high ambient ammonia, which they
      face in certain seasons of the year in the natural habitat.

PMID- 14660874
TI  - Antennal sensilla of grasshoppers (Orthoptera: Acrididae) in relation to food
      preferences and habits.
AB  - The external structure, i.e. number and distribution of sensillae on male and
      female antennae of 12 species of grasshoppers belonging to Pamphaginae,
      Catantopinae, Oedipodinae and Gomphocerinae in the grasslands of Inner Mongolia
      was investigated using scanning electron microscopy. Five major types of antennal
      sensillae were detected--trichoid, long basiconic, short basiconic, slender and
      short basiconic, and coeloconic sensillae. Total number of antennal sensillae
      varied among different sexes, subfamilies, feeding groups, life forms and eco
      forms. Males showed significantly more sensillae than females, due to presence of
      more short basiconic and coeloconic sensillae. Species under Catantopinae showed
      more long basiconic sensillae than the others. The Oedipodinae had the highest
      number of slender and short basiconic sensillae and coeloconic sensillae,
      followed by Catantopinae and Gomphocerinae; while Pamphaginae had the fewest. The
      total number of sensillae showed the same trend for these two types amongst the
      subfamilies as well, species which prefer habits on the ground possessed fewer
      antennal sensillae than species which prefer to stay on plants. The maximal
      number of antennal sensillae were observed in hygrophytous species, Chorthippus
      albomarginatus, in the 12 grasshopper species investigated, although the data is
      not statistically significant. The general trend which emerged was that species
      feeding on grass possessed more antennal sensillae, particularly coeloconic
      sensillae, compared to other feeding group species.

PMID- 14660875
TI  - Silk formation mechanisms in the larval salivary glands of Apis mellifera
      (Hymenoptera: Apidae).
AB  - The mechanism of silk formation in Apis mellifera salivary glands, during the 5th
      instar, was studied. Larval salivary glands were dissected and prepared for light
      and polarized light microscopy, as well as for scanning and transmission electron
      microscopy. The results showed that silk formation starts at the middle of the
      5th instar and finishes at the end of the same instar. This process begins in the
      distal secretory portion of the gland, going towards the proximal secretory
      portion; and from the periphery to the center of the gland lumen. The silk
      proteins are released from the secretory cells as a homogeneous substance that
      polymerizes in the lumen to form compact birefringent tactoids. Secondly, the
      water absorption from the lumen secretion, carried out by secretory and duct
      cells, promotes aggregation of the tactoids that form a spiral-shape filament
      with a zigzag pattern. This pattern is also the results of the silk compression
      in the gland lumen and represents a high concentration of macromolecularly well
      oriented silk proteins.

PMID- 14660876
TI  - Insights from stable light isotopes on enamel defects and weaning in Pliocene
      herbivores.
AB  - A high prevalence of enamel hypoplasia in several herbivores from the early
      Pliocene Langebaanweg locality, South Africa, indicates general systemic stress
      during the growing years of life. The presence of several linear enamel
      hypoplasias per tooth crown in many teeth further suggest that these stress
      events may be episodic. The delta18O values along tooth crowns of mandibular
      second molars of Sivatherium hendeyi (Artiodactyla, Giraffidae) were used to
      investigate the cause of the stress events in this tooth type. Results show that
      weaning in this fossil giraffid occurred at a similar ontogenetic age to that in
      extant giraffes, and that the observed enamel hypoplasia towards the base of this
      tooth type manifested post-weaning. Further, high-resolution oxygen isotope
      analyses across S. hendeyi third molars suggest that the entire development of
      defective tooth crowns occurred under conditions of increased aridity in which
      the cool, rainy part of the seasonal cycle was missing. The high prevalence of
      this defect in many herbivores suggests that climatic conditions were not
      favourable. This study reiterates the value of stable isotope analyses in
      determining both the behaviour of fossil animals and the environmental conditions
      that prevailed during tooth development.

PMID- 14660877
TI  - A skeletochronological study of growth, longevity, and age at sexual maturity in
      a population of Rana latastei (Amphibia, Anura).
AB  - Longevity and age at sexual maturity in an Italian population of Rana latastei
      were studied by skeletochronology performed on the phalanges. Frogs collected in
      1998 and 1999 by drift fences and pitfall traps were marked by toe-clipping.
      After marking, individuals were released and the cut phalanges were processed for
      skeletochronological analysis. The maximum age so far recorded was 3 years in
      males and 4 years in females. The smallest male and female that were sexually
      mature on the basis of histological analysis of the gonads were 36 and 35 mm
      snout vent length (SVL), respectively. In both sexes, most individuals were
      estimated to breed shortly after emergence from their first overwintering. Among
      the European Brown Frogs, Rana latastei appears to be one of the shortest-lived
      and one of the first to reach sexual maturity.

PMID- 14660878
TI  - Blood coagulation factor VIII: An overview.
AB  - Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for
      the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes
      hemophilia A, the most commonly inherited bleeding disorder. This review
      highlights current knowledge on selected aspects of FVIII in which both the
      scientist and the clinician should be interested.

PMID- 14660879
TI  - Predictors of outcome in patients with normal-pressure hydrocephalus.
AB  - Despite emerging knowledge of over 40 years, the postoperative results after
      shunt implantations in patients diagnosed for normal-pressure hydrocephalus (NPH)
      have not improved significantly in the last decade. For this reason, predictors
      have to be identified in order to preoperatively predict the course of disease.
      From 1982 to 2000, we examined in a prospective study 200 patients diagnosed for
      NPH. Of the patients who were surgically treated by a shunt implantation we could
      re-examine 155 (78%) in a mean time interval of 7 months after operation. The NPH
      was graduated according to the results of the intrathecal infusion test in an
      early state NPH (without brain atrophy) and late state NPH (with brain atrophy).
      In the study we focused our attention on the possible predictors: patient's age,
      length of disease, clinical signs--like gait ataxia, dementia and bladder
      incontinence, etiology idiopathic/secondary as well as implanted valve type and
      the value of resistance to cerebrospinal fluid outflow. To measure the outcome we
      used the NPH recovery rate, as statistical test the chi(2) according to Pearson.
      In 80 patients with an early stage NPH (without cerebral atrophy) and a short
      course of disease (<1 year), slightly distinct dementia and an implanted Miethke
      Dual-Switch valve were significant predictors for a positive postoperative
      outcome. The outflow resistance measured in the intrathecal infusion test showed
      only a minimal relevance for the outcome. Those 75 patients with a late state NPH
      (with cerebral atrophy) had a better outcome when dementia was not present, the
      outflow resistance was >20 mm Hg.min/ml, the CSF tap test was positive and a
      Miethke Dual-Switch valve was implanted.

PMID- 14660881
TI  - Hospitals in a globalized world: a view from Canada.
AB  - Globalization is a complex, multidimensional phenomenon that has already
      influenced the way hospitals operate and will increasingly impact the healthcare
      landscape and patients' experience worldwide. This paper briefly analyzes the
      direct and indirect effects of globalization on healthcare systems and services,
      mainly focusing on the experience of academic health sciences centres. Building
      their analysis on the belief that globalization is neither negative nor positive
      in itself, the authors compare alternative definitions of globalization, suggest
      possible ways in which it could impact health systems, examine how the role of
      large teaching and research institutions could evolve over the next decade or so,
      and put forward some fundamental questions faced by healthcare institutions. In
      the first part of the paper, the complex and multidimensional nature of
      globalization is analyzed and the highly polarized debate on the nature of this
      phenomenon briefly summarized. The second part focuses on the effects of
      globalization on health and healthcare. A pre-existing conceptual framework is
      used to analyze the complex linkages between globalization and health, and
      alternative scenarios are presented to illustrate the current and potential
      effects of international trade policies and regulations on health systems. In the
      third part, changes in hospitals' structure, organization and functions triggered
      by globalization and the introduction of new information and communication
      technologies are examined. The analysis is built around five main elements:
      patients, human resources, capital, information and funding. Finally, the paper
      highlights some of the most fundamental challenges, both practical and ethical,
      that healthcare institutions have to face in the transition to a new era of
      globalized health services.

PMID- 14660882
TI  - The role of teaching and research hospitals in improving global health (in a
      globalized world).
AB  - Globalization is impacting on Hong Kong and Australia in different ways, but the
      experience of the public healthcare systems in both jurisdictions suggests a need
      for teaching and research hospitals to refocus from the management of
      international patients to better meet the needs for global health. Traditional
      globalization suggests a stockpiling of capital--a focus on improving global
      health suggests dismantling the stockpiles and sharing access to the necessary
      data, information, knowledge and discoveries to further develop local health
      expertise. Consistent with its position as a leading healthcare provider, the
      University Health Network (UHN) has been reflecting on the impact of increasing
      globalization on hospitals. The goals of the UHN paper on globalization are
      threefold--to suggest how the external and internal environments of hospitals
      will change as a result of globalization; to suggest a role for hospitals in a
      globalized world; and to stimulate discussion and debate. Given our perspective,
      from the other side of the world, we are pleased to contribute to the discussion
      and debate but will limit our comments to the future role of teaching and
      research hospitals based on some of the experiences of Australia and Hong Kong.
      The citizens of Hong Kong have been acutely aware of the issue of globalization-
      the excellent deep-water harbour has ensured the position of Hong Kong as a major
      trading hub. Hong Kong has also had a continually evolving role as a financial
      centre and gateway to China, and with China's accession to the World Trade
      Organization the impact of globalization will be even greater. On the other hand,
      the citizens of Australia have lived with geographic isolation, relatively
      limited natural resources and a small population, all of which have limited their
      role in global trade and financial markets. However, both Hong Kong and Australia
      have seen recent benefits from the increasing speed of communication and
      information transfer and exchange. While it may still take close to a month for
      Australian practitioners to receive the hard copy of the journal in the mail, a
      electronic transfer is instantaneous. The globalization of knowledge and practice
      is one of the largest impacts of the Internet. With one of the most connected
      populations in the world, Hong Kong is very active in the sharing of knowledge
      with international experts.

PMID- 14660883
TI  - Globalization of medical services: antidote for rising costs.
AB  - The costs of medical services continue to rise despite a number of measures used
      to contain them. These costs, if not stemmed, will begin to compromise other
      priorities. Serious problems call for a bold step; and this bold step is to
      locate medical care facilities in low-cost overseas sites that are rich in high
      quality health human resources and have stable and sound governments. Issues
      pertaining to quality, acceptability, and other factors are surmountable
      problems.

PMID- 14660884
TI  - Globalization of healthcare: a U.K. perspective.
AB  - This commentary identifies the ability of the globalization of healthcare
      information and knowledge to empower populations and individuals. This, in turn,
      allows people to better hold to account the vested political and professional
      interests in order to provide or enable improvements to access and delivery of
      modern and effective health services. The author argues the importance of the
      wealth of the population to the availability of good healthcare and the
      contribution that healthcare industries and services could make to the economy of
      a particular country, notwithstanding its status as a developed, a developing or
      an underdeveloped nation.

PMID- 14660885
TI  - Patients in a globalized world: keeping hospitals in perspective.
AB  - The challenge of globalization could be the burning platform on which Canadian
      health providers finally learn that there is more to gain from collaboration than
      competition. Change in this globalized world cannot mean morphing into (publicly
      funded) entrepreneurial organizations and competing among other Canadian
      institutions prospecting for their global market share. Hospitals must understand
      that if they are firstly integrated into a proper, seamless healthcare system,
      they could then have extraordinary power in a globalized world. The VISA model
      should be examined as an example of the collaboration and co-operation that has
      allowed thousands of highly competitive financial institutions to come together
      with a common governance structure and an IT system that benefits everyone. VISA
      is doing very well in a globalized world. Perhaps it is because of our hospital
      centric approach to acute care that we have continued to view healthcare as
      simple or merely complicated instead of as a complex, adaptive system. Only by
      focusing on creating a (real) healthcare system here in Canada with the patient
      in the centre will we be able to ensure that Canadians will receive the benefits
      of globalization and that Canada will, as Commissioner Romanow said in his
      report, (take an international leadership role in sharing its expertise and
      helping developing countries improve their healthcare systems and the health of
      their people.)

PMID- 14660886
TI  - Hospitals in a globalized world: a view from the United States.

PMID- 14660887
TI  - Hospitals and academic health sciences centres: leaders or followers in health
      globalization?
AB  - The overall impact of globalization on health outcomes is contentious, but there
      is no doubt that knowledge transfer and the extension of specific health
      interventions to developing countries promise extraordinary benefits. It has been
      suggested that improved information/communications technology and the creation of
      distributed hospital systems leading a virtual healthcare web will permit
      realization of the promise of globalization. It is argued in this commentary that
      such evolution will require a new model of shared governance in the healthcare
      system. The leading vision is most likely to come from academic institutions,
      researchers, health professionals and governments. The "super-hospital" of the
      future should be expected to play a key role as service provider and partner.

PMID- 14660888
TI  - Providing services globally: the experience of an internet pharmacy.
AB  - Globalization of hospital-based medical services represents another step in the
      globalization of healthcare. The rise of transnational pharmaceutical firms
      represents an early example of the globalization of healthcare, which on the
      whole has provided many benefits. Medical discoveries made in one country are
      rapidly and seamlessly made available to patients in other parts of the world.
      Clinical research methodology has become much more sophisticated, and both the
      size and the scope of clinical studies have increased. Regulatory practices have
      developed to meet the highest national requirements and thus have served to
      improve standards worldwide. Globalization of hospital-based medical services may
      similarly serve as a catalyst to new methodologies and improve standards of
      service worldwide. Before such benefits can be realized, however, there are a
      number of regulatory and economic obstacles to overcome. An insight to some of
      these obstacles can be gleaned from the experiences of the Internet pharmacies.
      Provision of pharmacy services via the Internet has raised a number of regulatory
      and human resources issues. The revenue model is also instructive and has
      implications for the expectations of globalization as a source of revenue for
      hospitals. This paper will report on the development of one Internet pharmacy and
      the initiatives of other Internet pharmacies to overcome provincial and federal
      regulations limiting the provisions of services across borders. Some of these
      issues will also be problems for the provision of global medical services by
      hospitals as presented in the lead paper.

PMID- 14660890
TI  - The critical importance of leadership.

PMID- 14660891
TI  - Where are the healthcare leaders" the need for investment in leadership
      development.
AB  - Is there a crisis in healthcare leadership? In order to understand this question
      we must first look at what is meant by the term leadership. We prize and admire
      leadership skills, yet we have little understanding of how and why some persons
      are more effective leaders than others. This paper describes the changing concept
      of leadership in the context of both corporate and healthcare settings. The
      approaches taken in corporate leadership development programs are contrasted with
      the way in which leaders have been developed in healthcare. The authors assert
      that there are unique characteristics of health systems and organizations that
      warrant a tailored approach. A new model of developing healthcare leaders is
      proposed, one that could transform the educational process and improve outcomes.
      The authors call for a "back to basics" about how adults learn and outline an
      approach to leadership development in healthcare that includes principles of
      competency-based development, interdisciplinary and team learning and continuous
      assessment. Their conclusion is that leadership development is not done solely to
      improve the leadership skills of one individual but is an essential component of
      the development of the organization as a whole. Progressive health systems that
      invest in leadership development for the entire senior management team will have
      the more significant return on investment in terms of organizational
      effectiveness.

PMID- 14660892
TI  - Leadership demands creativity and vision--can they be taught?
AB  - Leatt and Porter offer views on the principles of leadership development for the
      future of healthcare and propose a "new model for developing healthcare leaders
      em leader that could transform the educational process and improve outcomes" for
      organizations as a whole. They maintain that the healthcare "educational process
      needs to be designed to enhance senior healthcare leaders' competency, prepare
      them for action and ultimately increase leadership and system performance and
      quality." As a tool to achieve these goals, Leatt and Porter present a model for
      learning based on 10 principles that, among other things, address what they see
      as the "need to increase our ability to identify, quantify, develop, measure and
      evaluate competencies for healthcare leaders." In the viewpoint of this
      commentator, written from his observations as a CEO, the most critical
      competencies in a leader, and the least susceptible to measurement, are
      creativity and vision. In the business world, as in the healthcare sector, these
      traits are absolutely necessary for leaders to deal effectively with known and
      unforeseen demands on their organizations, ongoing problems of scarce resources
      and, particularly in the Canadian healthcare sector, the need for leaders to
      negotiate with all levels of government to improve the system.

PMID- 14660893
TI  - Leadership: what works in the real healthcare world".
AB  - While the lead authors explore concepts of leadership from many dimensions, their
      observations stop short of practical discussion of leadership behaviour in the
      real healthcare world. This commentary calls for examination of the skills and
      abilities that strong leaders actually use to lead their organizations.

PMID- 14660894
TI  - Developing leaders in the real world.
AB  - Leatt and Porter present an excellent and timely review of the current leadership
      challenge in the field of healthcare administration. Their case is assembled
      through a review of relevant management literature and an adept summarization of
      current thinking and contemporary needs in the leadership zone of healthcare
      organizations. This commentator views the authors' thesis through the filters of
      a 30-year career as a healthcare administration practitioner and educator, the
      last 20 of which have been as a chief executive officer and concurrent
      professorial appointee at four universities in the United States. A leadership
      development paradigm at the UAB Health System is used to demonstrate an
      application of the lead authors' proposed, career-long development process
      encompassing graduate, postgraduate, mid-career and senior-executive levels.

PMID- 14660895
TI  - The role of health administration education in developing healthcare leaders.
AB  - Certain proposals are difficult to challenge and appear to be beyond debate. The
      call for improved quality of healthcare is one of these. And certainly, the call
      for more leaders and more highly skilled leaders in the healthcare industry is
      another, especially in these times of rapid change, strained resources and
      concern about quality. Though the goal of preparing more leaders, and in
      particular preparing more highly skilled leaders, is meritorious, the premises
      underlying this goal and the methods of achieving it deserve careful examination.
      This commentary questions the ability to accurately forecast the supply of and
      demand for leaders in the healthcare industry and examines selected aspects of
      the 10 principles for leadership development proposed in the lead paper.

PMID- 14660896
TI  - Identifying and assessing competencies: a strategy to improve healthcare
      leadership.
AB  - There appears to be a growing consensus that better leadership is needed in
      healthcare, although there is much less agreement on the specific knowledge and
      skills required to improve performance. This commentary suggests that the
      articulation of healthcare leadership and management competencies provides a
      framework and a language for identifying the leadership knowledge and skills
      required for high-quality healthcare in the 21st century.

PMID- 14660897
TI  - Expert leaders for healthcare administration.
AB  - This commentary explores the role of graduate programs in developing future
      leaders in health administration. The five-stage Dreyfus model for skill
      acquisition is applied to graduate education and continuing professional
      development, and barriers to producing the type of leader capable of transforming
      the healthcare system are discussed.

PMID- 14660898
TI  - Diverse circumstances require diverse styles.
AB  - What characterizes effective leaders and how can we train them so that the future
      of the healthcare field will be secure and successful" In the lead paper, Leatt
      and Porter do an excellent job of summarizing the leadership literature. They
      then comment on the challenges for the healthcare field. A problem with their
      analysis is the narrow focus on provider organizations and its attendant limited
      perspective. Also, further consideration should be given to graduate programs
      that are actively engaged in lifelong learning opportunities and the best
      educational practices they demonstrate.

PMID- 14660899
TI  - Is the graduate education model inappropriate for leadership development?
AB  - This commentary argues that the graduate education model is inappropriate for
      developing healthcare leaders. The model has served healthcare well in the
      development of researchers and other academics because it prepares them for a
      lifetime of success in scholarly publication. However, this model is
      inappropriate for developing healthcare leaders. What is required for leadership
      development is a practitioner-based learning model that focuses on developing
      emotional intelligence. As illustrated by the success of the Center for Creative
      Leadership, such a learning process involves experiential learning with and from
      peers in a supportive environment. The paper argues that future leaders must be
      provided with opportunities to reflect upon and refine their emotional responses
      to situations that call for leadership. Reflection and feedback on behaviour and
      emotions are the critical components of such learning. Cognitive understanding,
      the hallmark of the graduate education model, is but a small part of leadership
      development.

PMID- 14660900
TI  - "Nihil nocere" and beyond: the issue of leadership in healthcare.
AB  - The quality of leadership is usually assessed in terms of business performance,
      which is reflected in expenditure and revenue figures. Although cost efficiency
      becomes an ever more important factor in healthcare, financial revenue is not the
      only defining factor for quality of leadership in a business where the
      consequence of failure may be deadly in the true sense of the word. Moreover,
      since "health" and "well-being" are both complex issues involving a variety of
      psychological variables, customer satisfaction in this field is not always
      strictly related to the quality of the delivered care. This difficulty in the
      definition of an accomplished leader in healthcare may have added to the
      negligence in developing leadership in this field.

PMID- 14660901
TI  - Leadership in healthcare: better understanding of the challenges is required.
AB  - The healthcare system is facing unique challenges that are distinct from the
      issues that face any other type of organization or corporation. Leadership in
      this milieu requires an equally distinct set of skills and knowledge. Leatt and
      Porter offer a theoretical analysis of leadership development, yet more needs to
      be done to probe into the challenge of providing leadership in the healthcare
      continuum.

PMID- 14660903
TI  - Candidate's thesis: Platelet-activating factor-induced hearing loss: mediated by
      nitric oxide?
AB  - OBJECTIVES/HYPOTHESIS: Platelet-activating factor (PAF)in middle ear effusion is
      thought to induce hearing loss. The purpose of this study is to investigate the
      role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by
      studying the effects of PAF application on the round window membrane (RWM) with
      and without PAF-antagonist NO-blocker. STUDY DESIGN: Longitudinal study on
      randomized guinea pigs using PAF to induce hearing loss. METHODS Guinea pigs were
      divided into four groups: PBS, PAF, PAF-antagonist, and L-NAME. The PBS group
      received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and
      40 microg of PAF soaked into gelfoam and placed on the RWM. PAF-antagonist (WEB
      2170) and NOS inhibitor NG-nitro-l-arginine-methylester (L-NAME) were injected
      intraperitoneally prior to PAF 20 microg application on the RWM. The following
      three tests were performed on each animal group: Hearing was tested with an
      auditory brainstem response (ABR) test over 24 hours. At the end of 24 hours,
      cochlear hair cells were examined by scanning electron microscopy (SEM) and
      immunohistochemistry was carried out on the cochlea to test the expression of
      inducible nitric oxide synthase (iNOS). RESULTS: The PAF group developed
      significant elevation of ABR threshold and cochlear hair cell damage in the SEM
      group as compared with the PBS control group. The PAF-antagonist (WEB 2170) and
      the L-NAME groups did not show significant elevation of ABR threshold and
      cochlear hair cell damage compared with the group administered PAF 20 microg, but
      in the PAF-antagonist group, the elevation of ABR threshold was significant
      compared with that of the PBS control group, whereas it was not significant
      compared with the PBS group in the L-NAME group. Strong expression of iNOS on
      cochlea was observed in the PAF group and lighter expression was seen in PBS, WEB
      2170, and L-NAME groups. CONCLUSIONS: This study demonstrated that PAF placed on
      the RWM induced hearing loss and cochlear hair cell damage. The PAF-antagonists
      and L-NAME prevented the PAF-induced hearing loss and inhibited iNOS expression
      in the cochlea. These findings suggest that the PAF-induced hearing loss caused
      by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and L
      NAME may have future therapeutic implications in preventing sensorineural hearing
      loss associated with chronic otitis media. The results of this study have
      significant potential clinical application.

PMID- 14660904
TI  - A method to intraoperatively assess stapes prostheses for magnetic attraction.
AB  - OBJECTIVE: To present a technique used to assess metallic otologic prostheses for
      magnetic susceptibility during surgery. STUDY DESIGN: Description of a surgical
      technique. METHODS: A sterile handheld pacemaker magnet is used to evaluate the
      prosthesis prior to implantation. The magnet is placed over the prosthesis and
      the prosthesis is placed directly on the magnet. Any evidence of magnetic
      attraction and the prosthesis is rejected prior to implantation. RESULTS: None of
      the prostheses screened showed any magnetic attraction. As a control, steel wire
      was cut into pieces with dimensions similar to prostheses. These sections of wire
      were readily attracted to the magnet. CONCLUSIONS: Intraoperative screening of
      metallic prostheses for magnetic susceptibility is possible using a sterile
      handheld pacemaker magnet.

PMID- 14660905
TI  - Nasal glioma and encephalocele: diagnosis and management.
AB  - OBJECTIVE: To review the biology of nasal glioma and encephalocele and to present
      an algorithm for preoperative evaluation and surgical management. DESIGN:
      Retrospective review and analysis. SETTING: Tertiary care medical center: 1970 to
      2002. PATIENT: Sixteen patients with glioma (n = 10) and encephalocele (n = 6).
      OUTCOME: Age at the time of presentation, sex, signs and symptoms, imaging
      findings, surgical approach, pathology, complications, rate of recurrence, and
      follow-up were recorded. RESULTS: Ten patients presented with nasal glioma with a
      mean age of 9 months. All patients underwent surgical excision. No complication
      was encountered with a mean follow-up of 3.5 years. Six patients presented with
      encephaloceles with a mean age of 15.5 months. All patients underwent surgical
      excision. Complications included cerebrospinal fluid leak (n = 1) and epiphora (n
      = 1). Follow-up was 1 to 14 years (mean, 4 years). CONCLUSION: Nasal glioma and
      encephalocele are rare, benign, congenital lesions with a potential for
      intracranial extension. Evaluation should include a complete rhinologic and
      neurologic examination. Preoperative imaging with a thin-cut axial and coronal
      computed tomography scan and/or multiplanar magnetic resonance imaging is
      essential. Surgical intervention should be performed soon after diagnosis to
      alleviate the increased risk of meningitis. A frontal craniotomy approach is
      recommended if intracranial extension is identified based on preoperative
      evaluation, followed by an extracranial resection. If there is no evidence of
      intracranial extension, a conservative extracranial approach is recommended.

PMID- 14660906
TI  - Vascularized radial forearm free tissue transfer for lining in nasal
      reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: Total and near-total nasal reconstruction requires the
      surgeon to replace external nasal cover, skeletal support, and internal nasal
      lining. The successful result must re-create the form and function of the
      original nose. In large defects, traditional sources of internal lining may be
      unavailable. The study describes the recreation of nasal lining in three patients
      with extensive nasal defects with vascularized radial forearm tissue. STUDY
      DESIGN: Retrospective review of three patients who underwent nasal reconstruction
      with radial forearm for internal lining, costal cartilage grafts for skeletal
      support, and paramedian forehead flap for cover. METHODS: The charts of three
      patients who underwent total nasal reconstruction with radial forearm tissue
      transfer for lining were retrospectively reviewed. The technique was evaluated.
      The authors present a method for internal lining reconstruction in extensive
      nasal defects. They discuss the advantages and disadvantages of this method.
      RESULTS: Three patients underwent successful total nasal reconstruction with
      radial forearm tissue transfer for lining, costal cartilage for skeletal support,
      and paramedian forehead flap. None of the patients had adequate septal mucosa or
      nasal subunit skin to support mucosal rotation grafts or epithelial turn-in
      flaps. All patients have completed reconstruction and have satisfactory nasal
      form and function. Loss of the lining flap or graft loss did not occur.
      CONCLUSION: Vascularized radial forearm tissue supplies ample quantities of skin
      to recreate nasal lining. The tissue provides excellent support of graft
      material, and it prevents contracture of the covering flap. Because of its bulk
      and donor site morbidity, free forearm tissue transfer should not be considered
      for reconstruction of smaller defects when another lining flap will suffice.

PMID- 14660907
TI  - Esthesioneuroblastoma: endoscopic nasal and anterior craniotomy resection.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to illustrate the use of endoscopic
      techniques as an evolving surgical modality in excision of esthesioneuroblastoma.
      The authors advocate this method with excision with anterior craniotomy for
      removal of cribriform plate or anterior cranial fossa tumor extension. STUDY
      DESIGN: A retrospective chart review of patients with esthesioneuroblastoma
      treated surgically at a tertiary care institution from 1991 to 2002 using this
      surgical paradigm. METHODS: Patients were excluded for nonsurgical treatment or
      nasal and sinus tumor excision by nonendoscopic techniques. Patient demographics,
      tumor histological findings, presenting signs and symptoms, staging (Kadish and
      Dulguerov), postoperative complications, adjunct therapy, and recurrence were
      examined. RESULTS: Seven of 13 patients with esthesioneuroblastoma met all
      inclusion criteria. The average patient age was 47 years, with a male-to-female
      distribution of 4 to 3. Patients were grouped by tumor stage using Kadish (stages
      A, B, and C included three, one, and three patients, respectively) and Dulguerov
      (stages T1, T2, and T4 included three, two, and two patients, respectively)
      methods. Average follow-up was 62.3 months. All patients had an endoscopic
      excision of the nasal and sinus component with anterior craniotomy. The most
      common postoperative complication was temporary mental status change, which was
      seen in two patients. There were no postoperative deaths. All patients received
      radiation therapy, and one also received chemotherapy. Two of the seven patients
      had recurrences. At last follow-up, six patients had no evidence of disease and
      one was alive with disease. CONCLUSION: Endoscopic excision of the nasal and
      sinus component with anterior craniotomy for cribriform or anterior cranial fossa
      extension is an effective treatment of esthesioneuroblastoma.

PMID- 14660908
TI  - Short-term functional donor site morbidity after radial forearm fasciocutaneous
      free flap harvest.
AB  - OBJECTIVES/HYPOTHESIS: The existing literature on postoperative donor extremity
      function describes a spectrum of morbidity in the long term (>3 mo after
      surgery). However, the consensus is that there is minimal to no impact of flap
      harvest on patients' activities of daily living. No previous reports have
      examined functional donor site morbidity in the early postoperative period; such
      may affect patients' overall perioperative progress, especially with respect to
      donor extremity dominance. The authors' objective was to quantify functional
      morbidity of the donor site in radial forearm fasciocutaneous free flaps during
      the early postoperative period. STUDY DESIGN: Retrospective case series review.
      METHODS: Patient data were obtained from hospital records of 12 consecutive
      patients who underwent head and neck reconstruction with radial forearm
      fasciocutaneous free tissue transfer over a 6-month period at a tertiary academic
      medical center. Functional results of each patient's donor extremity obtained
      preoperatively and at 5 to 8 days after surgery were determined by quantifying
      forearm supination and pronation, wrist flexion and extension, and sharp and dull
      hand sensations in radial, median, and ulnar nerve distributions. RESULTS: Mean
      patient age was 57 years (age range, 42-71 y). The nondominant extremity was the
      donor site in 9 of 12 patients. Using the paired two-tailed t test, statistically
      significant differences were demonstrated in preoperative versus postoperative
      forearm supination (P <.032), pronation (P <.006), wrist flexion (P <.000), and
      wrist extension (P <.000). Three of 12 patients demonstrated diminished sharp
      sensation in the "anatomical snuffbox" distribution. CONCLUSION: The authors
      describe statistically significant functional forearm and wrist range-of-motion
      morbidity associated with the harvest of a radial forearm fasciocutaneous free
      flap in the early postoperative period.

PMID- 14660909
TI  - Amyloidosis of the upper aerodigestive tract.
AB  - OBJECTIVES/HYPOTHESIS: To delineate the clinical and pathologic characteristics
      of upper aerodigestive tract amyloidosis with particular attention to laryngeal
      amyloidosis. STUDY DESIGN: Retrospective chart review of patients with
      amyloidosis of Thomas Jefferson University and its affiliated hospitals. MATERIAL
      AND METHODS: The charts of 16 patients with upper aerodigestive tract amyloidosis
      identified from the databases of the Thomas Jefferson University pathology
      department were reviewed and included in the study. RESULTS: Sixteen patients (9
      male and 7 female, with an average age of 49.8 years) with upper aerodigestive
      tract amyloidosis were identified. The most common site of amyloid involvement
      was the larynx. Consequently, patients most commonly presented with hoarseness
      (14 of 16). All patients underwent surgical removal of the amyloid deposits.
      Fourteen patients had primary localized amyloidosis. Two experienced systemic
      involvement. Seven of the 16 patients developed recurrences requiring further
      treatment. CONCLUSIONS: Amyloidosis of the upper aerodigestive tract generally
      behaves as a benign, localized condition treatable by surgical resection. Regular
      follow-up with laryngoscopy is indicated for early diagnosis of recurrence, and
      multiple surgical procedures may be required to control symptoms.

PMID- 14660910
TI  - Clinical course of thyroid carcinoma after neck dissection.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to compare the rate and site of
      recurrences in patients with well-differentiated thyroid carcinoma who underwent
      a central compartment dissection, a posterolateral neck dissection, or a
      combination of both procedures. STUDY DESIGN: Retrospective chart review.
      METHODS: The charts of 522 consecutive patients with well-differentiated thyroid
      carcinoma were reviewed, and 74 patients who had undergone a neck dissection were
      identified. The rates of recurrence in three sites were noted: the central
      compartment nodes (levels VI, superior mediastinum), posterolateral compartment
      neck nodes (levels II-V), and distant sites. These rates were compared in
      patients who underwent a central compartment dissection (level VI, superior
      mediastinum) and in patients who underwent a posterolateral neck dissection
      (levels II-V). RESULTS: Six patients underwent only a central compartment
      dissection, 47 patients had only a posterolateral neck dissection, and 21
      patients had both a central compartment and a posterolateral neck dissection. In
      these three groups there were zero, two, and two central compartment node
      recurrences; two, nine, and seven posterolateral neck recurrences; and zero, two,
      and three distant recurrences, respectively. There were no significant
      differences in the rate of recurrence in any of the three sites examined between
      any of the three treatment groups (Fisher's Exact test, all P values >.20).
      CONCLUSION: In patients with well-differentiated thyroid carcinoma, dissection of
      only the central or posterolateral compartments of the neck with clinical or
      radiographic evidence of disease is advocated.

PMID- 14660911
TI  - Actinomycosis abscess of the thyroid gland.
AB  - OBJECTIVES: To present an unusual case of actinomycosis abscess of the thyroid
      gland as well as review the history, etiology, pathogenicity and treatment of
      actinomycosis infections of the head and neck. STUDY DESIGN: Case study. METHODS:
      A report of a 39 year-old female status post tooth extraction that developed an
      actinomycosis abscess of the thyroid. RESULTS: After a thyroid actinomycosis
      abscess was suggested by physical exam, ultrasound, CT scan and needle
      aspiration, an otolaryngology consult was obtained. The patient successfully was
      managed with thyroidectomy and intravenous ceftriaxone. CONCLUSIONS: Although
      Actinomycosis soft tissue infections of the head and neck are relatively
      uncommon, the head and neck surgeon must include it in the differential diagnosis
      when clinical presentation raises suspicion. Early biopsy is necessary for
      appropriate identification of the organism with the appearance of sulfur granules
      lending a clue to the diagnosis. Debridement and/or excision are often necessary
      for antibiotics to be used successfully. Antimicrobial therapy should be used for
      six to twelve months to completely eradicate the disease and prevent recurrence.

PMID- 14660912
TI  - One last peak.

PMID- 14660913
TI  - Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in
      pediatric patients with acute otitis media and otorrhea through tympanostomy
      tubes.
AB  - OBJECTIVE: To determine whether topical administration of a corticosteroid
      improves resolution of acute tympanostomy tube otorrhea when combined with
      topical antibiotic drops. STUDY DESIGN: Randomized, patient-masked, parallel
      group, multicenter trial of topical otic ciprofloxacin/dexamethasone versus
      topical ciprofloxacin alone in 201 children aged 6 months to 12 years with acute
      otitis media with tympanostomy tubes (AOMT) of less than or equal to 3 weeks'
      duration and visible otorrhea. METHODS: Eligible patients were randomized to
      receive three drops of either ciprofloxacin 0.3%/dexamethasone 0.1% or
      ciprofloxacin 0.3% into the affected ear or ears twice daily for 7 days. Clinical
      signs and symptoms of AOMT were evaluated on days 1 (baseline), 3, 8 (end-of
      therapy), and 14 (test-of-cure), and twice-daily assessments of otorrhea were
      recorded in patient diaries. RESULTS: The mean time to cessation of otorrhea in
      the microbiologically culture-positive patient population (n = 167) was
      significantly shorter with topical ciprofloxacin/dexamethasone than with
      ciprofloxacin alone (4.22 vs. 5.31 days; P =.004). This resulted in significantly
      better clinical responses on days 3 and 8 (P <.0001 and P =.0499, respectively).
      However, there were no significant differences between the two treatment groups
      in either the clinical response or the microbial eradication rate by day 14.
      CONCLUSIONS: Topical otic treatment with ciprofloxacin/dexamethasone is superior
      to treatment with ciprofloxacin alone and results in a faster clinical resolution
      in children with AOMT. The contribution of the corticosteroid in achieving a 20%
      reduction (1.1 day) in time to cessation of otorrhea is clinically meaningful and
      represents an important advance over single-agent antibiotic therapy.

PMID- 14660914
TI  - Canal wall reconstruction with Mimix hydroxyapatite cement: results in an animal
      model and case study.
AB  - OBJECTIVE/HYPOTHESIS: To assess Mimix hydroxyapatite cement for its applicability
      in canal wall reconstruction using the gerbil as a canal wall model. A case is
      presented to illustrate a novel technique of canal wall reconstruction using
      Mimix on the basis of the findings of our animal research. STUDY DESIGN: This was
      a preclinical study. METHODS: Ten Mongolian gerbils were implanted with Mimix,
      with the left side used to simulate mastoid obliteration and the right side used
      to simulate canal wall reconstruction. Pre- and postsurgery auditory-evoked
      brainstem responses were used to assess ototoxicity, and hematoxylin-eosin
      staining of histologic sections was used to assess inflammatory and foreign-body
      response and new bone formation. RESULTS: Rapid wound healing was achieved with
      each of the nine animals evaluated, with no erythema, edema, or drainage.
      Inspection of the ear canal at the time of sacrifice revealed no signs of otitis
      media and no middle ear effusions. Microscopic examination showed no inflammatory
      response or foreign-body reaction, good mucosalization on the side of the implant
      facing the bulla, and minimal fibrosis adjacent to the skin. Eight of nine
      specimens showed new woven bone ingrowth at the bone implant interface, with
      active osteoblasts and viable lacunae cells. There were no apparent fractures in
      the implanted material. CONCLUSIONS: Mimix hydroxyapatite cement is biocompatible
      and suitable for canal wall reconstruction in the animal model. The
      characteristics of this cement, namely its ability to set quickly in a moist
      environment, offer advantages over previously used cements for canal wall
      reconstruction.

PMID- 14660915
TI  - Immunohistochemical demonstration of vascular endothelial growth factor in
      vestibular schwannomas correlates to tumor growth rate.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent
      mediators of angiogenesis, which is a mandatory process during tumor growth. The
      present objectives were to determine expression of VEGF in vestibular schwannomas
      by immunohistochemistry and to examine a possible correlation with symptom
      duration, tumor size, or growth rate. STUDY DESIGN: Retrospective patient file
      review; immunohistochemistry and light microscopy of vestibular schwannomas
      removed by surgery. METHODS: Vestibular schwannomas from 18 patients were
      immunolabelled using a polyclonal antibody against VEGF, followed by light
      microscopy and blinded semiquantitation of VEGF expression. Fifteen patients had
      a well-defined tumor growth rate defined by repeated preoperative magnetic
      resonance imaging scans. RESULTS: All tumors showed expression of VEGF in the
      Schwann cell cytoplasm, with a more intense staining of the perinuclear region of
      some cells. The staining intensity varied from tumor to tumor, and
      semiquantitation revealed a significant correlation between VEGF expression and
      tumor growth rate, but not symptom duration or tumor size. CONCLUSION: VEGF is
      expressed in vestibular schwannomas and the level of expression correlates
      positively with tumor growth rate, but not with tumor size and symptom duration.
      We conclude that VEGF seems to be a factor involved in the growth of vestibular
      schwannomas.

PMID- 14660916
TI  - The effect of GJB2 allele variants on performance after cochlear implantation.
AB  - OBJECTIVES/HYPOTHESIS: It has been hypothesized that etiology of hearing loss may
      serve as an independent variable in performance after cochlear implantation. To
      test this hypothesis, the authors identified pediatric cochlear implant
      recipients with gap junction protein beta2 (GJB2)-related deafness. The study
      examines performance outcomes associated with GJB2 deafness-causing allele
      variants. STUDY DESIGN: Pediatric cochlear implant patients were screened for
      GJB2 allele variants; statistical comparisons were made with prospectively
      obtained performance measures. METHODS: From 181 children who participated in a
      nationwide cochlear implant research program, 122 children were identified with
      congenital nonsyndromic sensorineural hearing loss and invited to participate.
      Screening for GJB2 allele variants was completed for 55 children. The children
      were homogeneous with respect to age (8 or 9 y) and age at implant (before age 5
      y). All patients have previously undergone a prospective regimented battery of
      performance measures. RESULTS: Performance measures were compared between 22
      children with and 33 children without mutations to determine whether GJB2 status
      was a significant predictor of cochlear implant outcomes. Reading and cognitive
      outcomes were significantly dependent on connexin status. The group of children
      who tested positive for GJB2-related deafness scored significantly higher on a
      nonverbal cognitive measure, Block Design, and on a measure of reading
      comprehension. CONCLUSION: The isolated insult to the cochlea created by GJB2
      allele variants allows for preservation of central cognitive function. Better
      reading performance is seen in children with GJB2-related deafness.

PMID- 14660917
TI  - Inner ear decompression sickness and inner ear barotrauma in recreational divers:
      a long-term follow-up.
AB  - OBJECTIVES/HYPOTHESIS: The objectives were to report the authors' experience with
      the long-term follow-up of patients with diving-related inner ear decompression
      sickness and inner ear barotrauma and to discuss residual cochlear and vestibular
      damage in relation to the question of fitness to dive. STUDY DESIGN:
      Retrospective consecutive case series. METHODS: Eleven recreational divers with
      inner ear decompression sickness and nine with inner ear barotrauma (IEB) were
      followed. A complete otoneurological physical examination and laboratory
      evaluation were carried out. The latter included audiometry,
      electronystagmography, a rotatory chair test using the sinusoidal harmonic
      acceleration protocol, and computerized dynamic posturography. RESULTS: Residual
      cochleovestibular deficits were found in 10 (91%) of the patients with inner ear
      decompression sickness and 3 (33%) of those with IEB (P <.02, Fisher's Exact
      test; odds ratio, 20). A significantly shorter follow-up period was required for
      the inner ear barotrauma group (P <.05, simple t test) because three patients
      (33%) recovered completely within 1 month of the diving accident. Eight patients
      had residual vestibular deficits on follow-up, but only one (12.5%) was
      symptomatic. However, five (56%) of the nine patients who had a cochlear insult,
      as documented by follow-up audiometry, complained of significant hearing loss and
      tinnitus. CONCLUSION: Inner ear decompression sickness carries a high risk for
      residual inner ear damage despite hyperbaric oxygen recompression therapy. A
      favorable prognosis might be anticipated for inner ear barotrauma. The finding
      that most patients with residual vestibular deficits were asymptomatic at the
      time of follow-up emphasizes the need for a complete vestibular evaluation,
      including specific bedside testing and laboratory examinations, before a return
      to diving activity may be considered.

PMID- 14660918
TI  - Results of Caldwell-Luc after failed endoscopic middle meatus antrostomy in
      patients with chronic sinusitis.
AB  - OBJECTIVES/HYPOTHESIS: The Caldwell-Luc operation for treatment of medically
      refractory chronic maxillary sinusitis has largely been replaced by functional
      endoscopic sinus surgery. Despite this change, the Caldwell-Luc procedure still
      has well documented indications including treatment of both failed endoscopic
      middle meatus antrostomy and irreversible mucosal changes. The purpose of the
      study was to review the authors' experience and results of Caldwell-Luc procedure
      after failed endoscopic middle meatus antrostomy in patients clinically deemed to
      have irreversible mucosal changes. STUDY DESIGN: Retrospective review of
      preoperative and postoperative results of patients who underwent Caldwell-Luc
      procedure for refractory chronic maxillary sinusitis after failed endoscopic
      middle meatus antrostomy. METHODS: The preoperative and postoperative clinical
      course of patients treated with Caldwell-Luc procedure performed by a single
      surgeon between 1996 and 2001 were reviewed. Only patients with a history of
      chronic sinusitis after failed maximal medical therapy, no prior Caldwell-Luc
      procedure, prior endoscopic middle meatus antrostomy, and at least 6 months of
      follow-up were included. Outcome measurements including documented endoscopic
      examinations and the need for repeat surgery, and postoperative computed
      tomography scan results were evaluated to assess treatment success. RESULTS: The
      study involved 11 men and 26 women who underwent 50 Caldwell-Luc procedures.
      Caldwell-Luc procedure was performed bilaterally in 13 patients. The average
      number of prior endoscopic middle meatus antrostomies before Caldwell-Luc
      procedure was 2. Of all patients, 92% responded to surgical treatment as
      demonstrated by an endoscopic examination or computed tomography scan revealing a
      disease-free maxillary sinus. Repeat Caldwell-Luc procedure was required in 8.0%
      (n = 3) because of continued sinusitis. Two of the three cases with repeat
      Caldwell-Luc procedures demonstrated clinical improvement during follow-up.
      Average follow-up was 23.5 months. CONCLUSION: Caldwell-Luc procedure seems to be
      highly effective in the management of medically refractory chronic sinusitis
      after failed endoscopic middle meatus antrostomy. Caldwell-Luc procedure should
      remain in the otolaryngologist's surgical repertoire for these selected cases.

PMID- 14660919
TI  - Endonasal surgery for contact point headaches: a 10-year longitudinal study.
AB  - OBJECTIVE: Some migraine and cluster headaches may be triggered by stimulation of
      intranasal contact points via the trigeminovascular system. Endonasal surgery is
      successful in some patients, but long-term outcomes have not been reported. STUDY
      DESIGN: Prospective. METHODS: This investigation included 20 patients with a mean
      18-year history of refractory cluster or migraine headaches who were selected for
      surgery. All had endoscopically visible endonasal contact as well as a positive
      preoperative cocaine test result. Changes in pain severity and frequency and
      duration of headache attacks were statistically rated using a MANOVA. Follow-up
      averaged 112 months. RESULTS: Almost 10 years after surgery, six patients
      remained completely free of pain, seven had significant symptom improvement, and
      seven received no benefit from surgery (65% improvement). Two patients had been
      free of all symptoms for 7 and 8 years, respectively, before complaints returned.
      CONCLUSION: Our data suggest that some patients with refractory headaches and
      endonasal contact areas benefit from surgery, thereby supporting the existence of
      a connection between the two. Even though it is clear that surgery should be
      considered only if all other treatments have failed, a success rate of 65% over
      almost 10 years justifies evaluation of this option. Preoperative patient
      selection remains crucial and warrants further investigation.

PMID- 14660920
TI  - Pathogenetic mechanism of olfactory cell injury after exposure to sulfur dioxide
      in mice.
AB  - OBJECTIVES: This study aimed to investigate the cellular pathogenetic mechanism
      involved in olfactory tissue injury and regeneration. STUDY DESIGN: Adult male
      mice were exposed to 40 ppm SO2 for 2 hours. METHODS: The mice were sacrificed
      immediately, 4 hours, and 1, 3, 5, 7, 10, 14, and 21 days after exposure to SO2.
      Olfactory neuroepithelium and bulbs were harvested at the time of sacrifice.
      Western blot and immunohistochemical staining were performed. RESULTS: Injuries
      of the olfactory neuroepithelium were found 24 hours after exposure to SO2. The
      number of total olfactory neuroepithelial cells decreased after SO2 exposure and
      recovered after 3 weeks. In contrast, the number of proliferating cell nuclear
      antigen (PCNA)-positive cells increased after SO2 injury and then decreased. In
      the neuroepithelium, where PCNA expression increased, olfactory marker protein
      (OMP)-positive cells were sparse. The expression of inducible nitric oxide
      synthase (iNOS) was localized in the lateral half of the turbinates. However,
      there was no expression of iNOS in the medial half of the turbinates, in which
      PCNA was strongly expressed. There was increased immunoreactivity of neuronal NOS
      (nNOS) in the surviving cells after SO2 exposure. Immediately after exposure to
      SO2, the immunoreactivity to phosphorylated fraction of extracellular signal
      regulated kinases (phospho-ERK)-1/2 increased in the cytoplasm and nucleus of
      supporting cells. In Western blot analysis, nNOS expression increased 4 hours
      after SO2 exposure. CONCLUSIONS: These findings suggest that the regenerative
      activity of the neuroepithelium might be well demonstrated by PCNA
      immunoreactivity and that regeneration of the neuroepithelium can be activated
      several days after SO2 injury. The two NOS isoforms, iNOS and nNOS, might
      contribute to neuroprotection in the olfactory neuroepithelium.

PMID- 14660921
TI  - Paranasal sinus bony structures and sinus functioning during viral colds in
      subjects with and without a history of recurrent sinusitis.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to assess the impact of ostial
      obstruction and anatomical variations on paranasal sinus functioning during viral
      colds with computed tomography (CT) in subjects with and without a history of
      sinusitis. STUDY DESIGN: Cross-sectional study. METHODS: Twenty-three volunteers
      with a history of recurrent sinusitis and 25 subjects without such history who
      had an early (symptoms for 2-4 d) natural cold were examined by taking viral
      specimens and CT scans and recording symptoms. The pathological sinus changes in
      the CT scans were scored, and several paranasal bony anatomical variations
      recorded. RESULTS: Viral origin of the cold was identified in 32 (67%) subjects,
      similarly in the two groups. Ostiomeatal obstruction and anatomical variations
      were equally frequent in the subjects with and without a sinusitis history (17 of
      23 vs. 17 of 25 for ostial obstruction and 17 of 23 vs. 20 of 25 for at least one
      variation, respectively). However, in the case of ostiomeatal obstruction the
      combined CT score of ethmoidal and maxillary sinuses was significantly higher in
      the subjects with a sinusitis history than in those without (mean +/- SD, 3.0 +/-
      0.9 vs. 2.3 +/- 1.2 [P =.05, t test]). In the sinusitis-prone subjects, several
      variations were associated significantly with various pathological sinus CT
      changes (septal deviation, horizontally situated processus uncinatus, large
      concha bullosa, and laterally concave concha media), whereas in the control
      subjects, only the presence of Haller cells was related to sphenoidal sinus
      disease. CONCLUSION: Ostiomeatal complex obstruction and bony anatomical
      variations seem to have a greater impact on the functioning of paranasal sinuses
      during viral colds in sinusitis-prone subjects than in subjects without a
      sinusitis history. These differences may be associated with the increased risk of
      bacterial sinusitis.

PMID- 14660922
TI  - Postoperative pain and side effects after uvulopalatopharyngoplasty, laser
      assisted uvulopalatoplasty, and radiofrequency tissue volume reduction in primary
      snoring.
AB  - OBJECTIVES: We compared, in a prospective study, the side effects and the
      postoperative complications of three procedures commonly used for the treatment
      of primary snoring. METHOD: Forty-nine patients underwent velopharyngeal surgery
      for primary snoring (17 for uvulopalatopharyngoplasty [UPPP]; 15 for laser
      assisted uvulopalatoplasty [LAUP], and 17 for radiofrequency tissue volume
      reduction [RFTVR]). Preoperative full polysomnographic studies ruled out
      obstructive sleep apnea syndrome. Each patient's evaluation encompassed
      postoperative pharyngeal pain (as measured by a 5-point visual analogue scale)
      and use of narcotic drugs in the early postoperative period as well as a
      subjective evaluation of late postoperative complaints. A surgeon's examination
      was performed to report postoperative complications in the oropharynx. RESULTS:
      Postoperative pharyngeal pain was less important in the RFTVR group than in the
      UPPP and LAUP groups. Mean scores at days 3, 7, 16 were as follows: 4.2, 4.0, and
      2.4, respectively, for UPPP; 4.6, 3.8, and 1.6 for LAUP; and 2.4, 2.0, and 0.7
      for RFTVR. Mean duration of pain with a score greater than 2 was calculated as
      follows: UPPP, 21.3 days; LAUP, 15.1 days; and RFTVR, 6.1 days. Mean duration of
      narcotic drug use for the patients who needed this medication was 10.1 days for
      UPPP, 7.2 days for LAUP, and 1.3 for RFTVR. Postoperative side effects (trouble
      with smell and taste, pharyngeal dryness, globus sensation, voice change, and
      pharyngonasal reflux) were more present in the UPPP and LAUP groups than in the
      RFTVR group. Surgeon's assessment for postoperative complications reported more
      wound infection, dehiscence, and posterior pillar narrowing in the UPPP and LAUP
      groups than in the RFTVR group. CONCLUSION: RFTVR is a safer and less painful
      procedure than UPPP and LAUP for the treatment of primary snoring. Postoperative
      discomfort after LAUP and after UPPP appears to be very similar.

PMID- 14660923
TI  - Intralesional cidofovir and surgical excision for laryngeal papillomatosis.
AB  - OBJECTIVE: To evaluate the efficacy of cidofovir intralesional therapy in
      recurrent respiratory papillomatosis and the role of surgical excision as an
      associated treatment. STUDY DESIGN: Prospective study and case series. METHOD:
      Twenty-six patients received intralesional cidofovir. Three endoscopies were
      performed at monthly intervals, with intralesion injections of cidofovir at 5
      mg/mL. Further endoscopic evaluation was made at 3 or 6 months depending on
      whether there was persistent papillomatosis. Cidofovir was again injected in the
      case of persistent papillomas, and treatment was repeated as long as papillomas
      were observed. Surgical excision of the papilloma was only performed in cases of
      airway obstruction or in cases proving resistant to cidofovir. RESULTS: Complete
      remission was obtained in 8 (31%) patients after an average of 2.6 endoscopic
      treatment. Seventeen (65%) patients presented slight or mild disease at endpoint
      (final severity score 1-4). Significant results were obtained in both adults and
      children. A greater response was obtained in the supraglottis and glottis
      subsites than in subglottis, tracheal, and other sites. Patients conforming to
      the 1 month interinjection schedule showed better responses in supraglottis
      subsite than those receiving their injections with intervals longer than 1 month.
      Combined therapy (cidofovir plus excision) was necessary in persistent
      papillomas. No patients presented with any systemic or local side effects.
      CONCLUSIONS: Cidofovir therapy was an effective treatment in adults and in
      children, allowing papillomatosis to be controlled without observed side effects.
      Surgical excision associated with cidofovir injections remained necessary in
      persistent papillomatosis after cidofovir treatment.

PMID- 14660924
TI  - Voice rest after microlaryngoscopy: current opinion and practice.
AB  - OBJECTIVE: Although voice rest is often recommended after excision of benign
      mucosal vocal fold lesions, no standard of care exists regarding the use,
      duration, or extent of vocal restrictions. This prospective study is intended to
      explore current opinions and practices of otolaryngologists regarding the use of
      complete and relative voice rest. STUDY DESIGN AND METHODS: A 16-item survey was
      mailed to all active U.S. members of the American Academy of Otolaryngology-Head
      and Neck Surgery (n = 7,321) regarding use of complete and relative voice rest
      after surgical excision of vocal fold nodules, polyps, and cysts. Treatment
      preference questions used a Likert 5-point scale with end anchors of 1 equaling
      "never" and 5 equaling "always". RESULTS: The response rate was 16.5% (1,208
      respondents). Differences by lesion type were not statistically significant,
      suggesting that surgeons consider the mucosal disruption resulting from the
      surgery to be similar across lesions. Approximately 51.4% (620) favored complete
      voice rest. Approximately 62.3% (753) favored relative voice rest. Approximately
      18% (213) of the respondents who "always" recommend complete rest also "always"
      recommend relative rest. The most common duration for both types of rest is 7
      days. CONCLUSIONS: There is a clear preference for the use of voice rest, but the
      specific type (complete or relative) is controversial, and a notable percentage
      of respondents (15%) do not favor any type of voice rest. It is likely that the
      lack of uniformity of opinions and practices reflects the absence of empirical
      data. Prospective clinical trials are needed to guide clinical standards of care.

PMID- 14660925
TI  - Distribution of collagen in the lamina propria of the human vocal fold.
AB  - OBJECTIVES: To describe the arrangement of collagen fibers in the lamina propria
      of the human vocal fold. STUDY DESIGN: Analysis of the lamina propria of the
      vocal fold obtained from human cadavers. METHODS: The Picrosirius-polarization
      method was used to visualize collagen fibers. RESULTS: Analysis of 20 human vocal
      folds by the Picrosirius-polarization method permitted the visualization of two
      fiber populations arranged in three layers in the lamina propria: two layers of
      thick, strongly birefringent collagen fibers (collagen type I), one immediately
      below the epithelium and another more dense layer in the deep region
      superficially to the vocal muscle, penetrating between muscle fibers. The third
      layer consisted of fine, weakly birefringent fibers (collagen type III) located
      between the two layers of thick fibers. In addition, the collagen fibers in the
      lamina propria showed an intertwined network arrangement in the form of a "wicker
      basket." CONCLUSIONS: This basket-like configuration better explains how the
      vocal fold is able to stretch even though it contains nonstretchable fibers and
      to modulate the frequency of the voice under the action of the intrinsic
      musculature of the larynx. Segmental areas of disarray of the basket-like
      structure of the collagen layers were systematically observed in older patients.
      Thus, it is possible that vocal alterations occurring in the elderly might be the
      result of a loss of histoarchitectural arrangement of the collagen system and its
      relationship with the lamina propria and underlying musculature.

PMID- 14660926
TI  - Laryngeal dystonia causing inspiratory stridor in children with cerebral palsy.
AB  - SUMMARY: OBJECTIVE To present three cases of inspiratory stridor caused by
      laryngeal dystonia (LD) in children with cerebral palsy (CP), one of whom is
      being treated by periodic botulinum toxin type A (BTX) injection into a vocalis
      muscle, thereby avoiding tracheostomy. STUDY DESIGN Case series. RESULTS AND
      CONCLUSIONS Laryngeal dystonia was diagnosed in three children with CP who
      presented with inspiratory stridor associated with generalized dystonia, all of
      whom were thought previously to have had laryngomalacia. The inspiratory stridor
      was severe enough in one patient that a tracheostomy was planned. In common with
      the movement disorder of generalized dystonia, the inspiratory stridor caused by
      LD was present in our patients when they were awake, worse when they were excited
      or agitated, diminished when they were awake and calm, and absent when they were
      asleep. Although there is overlap between the symptoms of LD and laryngomalacia
      (and other structural causes of upper airway obstruction) in children with CP,
      structural causes result in inspiratory stridor that is often persistent when
      patients are awake and relaxed or when they are asleep. Fiberoptic laryngoscopy
      in an awake patient with LD reveals vocal cord adduction in inspiration causing
      inspiratory stridor in association with generalized dystonia. Baclofen and
      gabapentin used together relieved the inspiratory stridor and improved the
      generalized dystonia of two patients, confirming the clinical diagnosis of LD,
      but for the last 2 years the third patient (the one with the most severe
      inspiratory stridor) also has required a periodic BTX injection into a vocalis
      muscle (the major vocal cord adductor) to relieve her inspiratory stridor,
      alternating the side of injection. Her mother considers this is a small price to
      pay to avoid tracheostomy. This is the first report of LD causing inspiratory
      stridor in patients with CP and the first reported use of BTX injection into a
      vocalis muscle for relief of inspiratory stridor due to LD in a child.

PMID- 14660927
TI  - Parathyroid hormone: an early predictor of postthyroidectomy hypocalcemia.
AB  - OBJECTIVE: To determine whether there is a correlation between the level of
      parathyroid hormone (PTH) soon after thyroidectomy and the development of
      hypocalcemia. STUDY DESIGN: Prospective series of 40 consecutive patients
      undergoing total thyroidectomy or completion thyroidectomy between January 2001
      and October 2002. METHOD: Ionized calcium was measured before surgery and at 1,
      6, 18, 30, and 42 hours after surgery. PTH was measured before surgery and at 1
      and 6 hours after surgery using an assay that accurately measures low levels of
      PTH. Patients were followed up at 1 week and 3 months after surgery with respect
      to their symptoms and need for calcium supplementation. Clinically significant
      hypocalcemia was defined as an ionized calcium level of less than or equal to 0.9
      mmol/L. RESULTS: The incidence of postoperative hypocalcemia was 30% (12/40). The
      mean PTH level 1 hour after surgery was much lower in patients who ultimately
      became hypocalcemic than in those who remained normocalcemic (3.8+/- 1.9 vs. 33
      +/- 21 pg/mL, P =.001). All patients with a PTH level less than or equal to 8
      pg/mL 1 hour after surgery developed hypocalcemia, whereas all those with greater
      than or equal to 9 pg/mL remained normocalcemic. CONCLUSIONS: A single PTH level
      of less than or equal to 8 pg/mL 1 hour postthyroidectomy is a strong predictor
      for the development of clinically significant hypocalcemia. Once validated, this
      test may serve to identify those who require more intensive monitoring, prompt
      early therapy in those deemed at risk, and enable confident early discharge in
      the majority of thyroidectomy patients.

PMID- 14660928
TI  - Hypopharyngeal acid exposure: an independent risk factor for laryngeal cancer?
AB  - OBJECTIVES/HYPOTHESIS: Gastroesophageal reflux disease has in recent years been
      linked to a variety of extraesophageal conditions including laryngeal cancer.
      However, whether a causal relationship exists is still under debate. The present
      study aimed to compare the occurrence and severity of gastroesophago
      hypopharyngeal reflux in patients with laryngeal cancer with those of healthy
      volunteers. STUDY DESIGN: Prospective, controlled study. METHODS Forty-one
      consecutive patients with newly diagnosed laryngeal cancer were examined by
      esophageal manometry and an ambulatory, 24-hour, double-probe pH monitoring.
      Their results were compared with those of 40 healthy volunteers. RESULTS:
      Hypopharyngeal acid exposure was registered mainly in the upright body position.
      A pathological acid exposure, as compared with the upper levels of normality
      among the healthy volunteers, was found in the hypopharynx in six (16%) patients
      with laryngeal cancer and in the distal esophagus in 10 (25%) patients.
      Pathological acid exposure in either location was found in 15 (37%) patients and
      in both locations in 1 (3%) patient. However, the mean acid exposure time and the
      mean value of the number of reflux events did not differ significantly between
      cancer patients and control subjects at either location. The exclusion of meal
      periods from the analysis did not alter these observations. Nonsmoking cancer
      patients (n = 5) and nonsmoking control subjects (n = 36) had similar acid
      exposure both in the hypopharynx and in the distal esophagus. CONCLUSION: The
      present results do not support gastroesophago-hypopharyngeal reflux as being an
      independent risk factor for laryngeal cancer.

PMID- 14660929
TI  - The effect of leukocyte interleukin injection (Multikine) treatment on the
      peritumoral and intratumoral subpopulation of mononuclear cells and on tumor
      epithelia: a possible new approach to augmenting sensitivity to radiation therapy
      and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.
AB  - OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the
      effect of the administration of a novel immunoadjuvant, leukocyte interleukin
      injection, as part of an immuno-augmenting treatment regimen on the peritumoral
      and intratumoral subpopulations of the tumor infiltrating mononuclear cells and
      on the epithelial and stromal components, when administered to patients with
      advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as
      compared with disease-matched control patients (not treated with leukocyte
      interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial.
      Fifty-four patients from four clinical centers were included in the dose
      escalating study (27 in each group [leukocyte interleukin injection-treated and
      control groups]). Cumulative leukocyte inter-leukin injection doses were 2400,
      4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor
      samples obtained at surgical resection of the residual tumor (between days 21 and
      28 after treatment initiation) were used. Histological analysis, necrosis
      evaluation, and American Joint Committee on Cancer grading were performed from
      H&E-stained sections. Immunohistochemical analysis was performed on three
      different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma
      interface, zone 3). Trichrome staining was used to evaluate connective tissue,
      and morphometric measurements were made using ImagePro analysis software. Cell
      cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin
      injection treatment induced a shift from stromal infiltrating T cells toward
      intraepithelial T cells and posted a significant (P <.05) increase in
      intraepithelial CD3-positive T cells independent of the leukocyte interleukin
      injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL
      2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte
      interleukin injection dose (P <.05). Furthermore, both low- and medium-dose
      leukocyte interleukin injection treatment induced a significant (P <.05) increase
      in the number of cycling tumor cells, as compared with control values.
      CONCLUSION: The results could be highly beneficial for patients with oral
      squamous cell carcinoma. First, leukocyte interleukin injection treatment induces
      T-cell migration into cancer nests and, second, noncycling cancer cells may enter
      cell cycling on administration of leukocyte interleukin injection. This latter
      effect may modulate the susceptibility of cancer cells to radiation therapy and
      chemotherapy. The findings may indicate a need to re-evaluate the way in which
      follow-up treatment (with radiation therapy and chemotherapy) of patients with
      head and neck cancer is currently approached.

PMID- 14660930
TI  - Modified Bondy's technique for epitympanic cholesteatoma.

PMID- 14660931
TI  - Subglottic stenosis in Wegener's granulomatosis and the nitinol stent.

PMID- 14660932
TI  - Transcutaneous chordal injection with a curved needle.

PMID- 14660933
TI  - Obituary: William W. Montgomery, MD.

PMID- 14660936
TI  - The case of Ms. M. Should an ethics consultant serve as a patient advocate?

PMID- 14660938
TI  - Privacy under HIPAA: what employers and providers need to know.

PMID- 14660939
TI  - Use of restraints on dementia patients: an ethical dilemma of a nursing staff in
      Israel.
AB  - This quality improvement project investigates the ethical dilemmas faced by
      nursing staff (ie, registered nurses, practical nurses, and nurse aids) using
      restraints for dementia patients in "realistic" and "idealistic" situations.
      RATIONALE: There is a need to offer adequate care for a growing number of
      patients suffering from dementia and to ensure their safety. Restraints are a
      common practice for this purpose; however, they may inflict harm and contradict
      patient rights of freedom, autonomy, and respect. The issue becomes more complex
      in view of the multiple studies showing that the various justifications for using
      restraints are often based on caregiver interests and institutional
      considerations rather than on the patient's benefit. DESIGN: The project was
      conducted on a sample of 200 Israeli nursing staff members, half from internal
      medicine wards of 3 hospitals and the other half from 3 psychogeriatric nursing
      homes, all treating dementia patients. The project used a questionnaire composed
      of demographic data and an ethical preference questionnaire built on 18
      situations concerning restraints. Situations were categorized into 3 purposes:
      (a) patient's benefit, (b) other patients' benefit, and (c) institutional
      benefit. These situations referred to realistic (ie, expressing views of daily
      practice) and idealistic (ie, expressing personal and professional beliefs and
      values) situations. RESULTS: The project exposes a discrepancy between the manner
      in which the nursing staff perceive use of restraints in an idealistic situation
      and in a realistic situation and the greater tendency to use restraints in the
      realistic situation than in the idealistic situation. The main contribution of
      the project is in revealing the conflict between the personal beliefs of the
      nursing staff and the nurses' perceptions of their institutional obligations.
      CONCLUSIONS: The project uncovered a discrepancy among the beliefs, the personal
      and professional values of the nursing staff, and their perception regarding the
      actual use of restraints in the daily work routine.

PMID- 14660940
TI  - The Hospital Ethical Climate Survey in Turkey.
AB  - This study was planned to assess the validity and reliability of the Hospital
      Ethical Climate Survey (Olson, 1995) in Turkey and to determine how nurses
      perceive the ethical climate of their working environment. The study was
      conducted on 276 nurses working in university, social insurance, state, and
      private hospitals. Five subfactors measured: assessment of the relationships
      between unit/department, manager, hospital, colleague, and doctors based on
      ethical climate. Significant differences were found, showing that the type of
      hospital greatly affected the level of positive perception as did the age of the
      nurse and the unit on which they worked.

PMID- 14660941
TI  - The link between perceived adequacy of preparation to practice, nursing error,
      and perceived difficulty of entry-level practice.

PMID- 14660942
TI  - Supporting innovations in midwifery education.

PMID- 14660943
TI  - Our students: a breath of fresh air.

PMID- 14660944
TI  - Innovations in midwifery education.
AB  - Midwifery educators and the American College of Nurse-Midwives (ACNM) have
      created educational pathways for Certified Nurse-Midwives (CNMs) and Certified
      Midwives (CMs) based on sound principles and creativity. A review of these
      educational innovations portrays the strong foundation that exists and provides
      direction for the future. Accreditation of educational programs, the development
      of core competencies, and the certification process for graduates of midwifery
      education programs form the foundation for excellence in midwifery education,
      while the early development of the modular mastery learning curriculum provided a
      transition to later use of telecommunications and the incorporation of various
      instructional technologies into midwifery education. Midwifery educators have
      continued to innovate with distance-learning, Web-enhanced curricula and
      community-based clinical preceptorships, and a master's degree in midwifery
      option to increase access to midwifery education and degree programs. Continued
      innovation and creativity will be required to prepare midwives for the 21st
      century.

PMID- 14660945
TI  - Clinical teaching and learning in midwifery and women's health.
AB  - Although there is an abundance of literature about clinical teaching in the
      health professions, a much smaller body of information focuses on the art and
      science of clinical teaching in midwifery and women's health. We reviewed
      preceptor handbooks, training manuals, and Web sites created by nursing and nurse
      midwifery education programs, medical and pharmacy schools, and national
      associations of health professionals. Using the search terms "clinical teaching,
      clinical learning, preceptor, clerkship, residency training, and midwifery
      education", we searched the MEDLINE and CINAHL databases and health sciences
      libraries for relevant articles and books. The information and practical
      strategies about clinical teaching that we found are synthesized and presented in
      this article. It includes a discussion of challenges in clinical teaching; an
      overview of expectations and responsibilities of the education program, students,
      and preceptors; suggestions about orienting students to clinical sites; clinical
      teaching strategies and skills; suggestions for incorporating critical thinking
      and evidence-based care into clinical teaching; guidelines for giving
      constructive feedback and evaluation; characteristics of excellent clinical
      teachers; and suggestions about how education programs and professional
      associations can support and develop clinical sites and preceptors. The Appendix
      contains manuals, books, and Web sites devoted to clinical teaching.

PMID- 14660946
TI  - Redesigning courses for the World Wide Web.
AB  - The use of computer-based instructional technologies has become almost ubiquitous
      in education, including health professions education. In addition, clinical
      practice requires the use of digital information, networking, and continued
      learning. Faculty, students, and clinicians must be prepared to use computer
      based technologies and telecommunications. Many faculty members in the health
      professions need assistance with the transfer of traditional (campus-based)
      courses or course material to the World Wide Web. This article presents the
      instructional design and pedagogical aspects of redesigning a traditional campus
      based course for the World Wide Web. Specific steps and a template are
      identified. The development of a virtual community of learners is also discussed
      as a critical element of on-line teaching and learning.

PMID- 14660947
TI  - The transition to Web-based education: enhancing access to graduate education for
      women's health providers.
AB  - Nurse-midwives and women's health nurse practitioners have a long history as
      positive change agents in health care as well as education. This article
      chronicles the transition of a traditional face-to-face nurse-midwife and women's
      health nurse practitioner graduate curriculum to a Web-based format with campus
      seminars and clinical laboratories. This change was made to increase access to
      these graduate programs. A total of 20 courses, including both graduate core and
      specialty courses, was converted to the Web-based format over a 3-year period.
      Practical considerations for implementing a similar program, including faculty
      development and support, student orientation and ongoing support, development of
      a learning community, and time management, are discussed. The importance of
      listening to student feedback and partnering with them as the program continues
      to develop is emphasized as a key element of program evaluation and improvement.

PMID- 14660948
TI  - Evaluation strategies for midwifery education linked to digital media and
      distance delivery technology.
AB  - The goal of the teaching and learning process for health professionals is the
      acquisition of a fundamental core of knowledge, the demonstration of critical
      thinking ability, and the demonstration of competency in the performance of
      clinical skills. Teaching and learning in distance education programs require
      that the administration, teachers, and students be creative in developing
      evaluation strategies that can be adapted to the challenges of the cyberspace on
      line educational environment. Evaluation standards for distance education
      programs recently have been delineated by federal agencies, private
      organizations, and academic accreditation associations. These standards are
      linked to principles of sound education practice that promote program quality,
      high levels of student-faculty interaction, and support effective teaching and
      learning in the distance education context. A growing body of evidence supports
      the conclusion that technology-enhanced teaching is equivalent in effectiveness
      compared with traditional methods when student-learning outcomes are the focus of
      measurement. An allied body of literature offers model approaches that can be
      useful to educators who must also conduct the evaluation of clinical skills,
      provide feedback, and promote socialization to the nurse-midwifery/midwifery role
      for students being educated in whole or in part through instruction delivered at
      a distance.

PMID- 14660950
TI  - Service learning: applications in midwifery education.
AB  - Service learning is learning acquired through experiential education that
      deliberately links service to others with the goal of achieving specific academic
      objectives. Service learning is an educational innovation that encompasses a wide
      range of activities and pedagogies while maintaining a commitment to principles
      of service. Although midwifery is a profession rooted in service to women and
      their families, scant attention has been paid to the purposeful inclusion of
      service-learning experiences in midwifery curricula. This article describes
      service learning and discusses practical applications in midwifery education.

PMID- 14660949
TI  - Web-based data collection in midwifery clinical education.
AB  - A Web-based computerized database for clinical data collection use by midwifery
      and nurse practitioner students was developed and revised over 2 years. The
      database provided insight into the number and diversity of clients seen as well
      as the student's level of autonomy. Students documented a selected set of data
      elements sensitive to nursing and midwifery care for all client encounters.
      Analysis of the clinical encounter data entered by nurse-midwifery students in
      the Antepartum Care course during two winter semesters included 1,417 client
      encounters. Results of the analyses are presented as well as educational and
      clinical issues involved in the development and maintenance of the database.
      Future work includes refining the current database, expanding the data set to
      include the ACNM nurse-midwifery clinical data sets for antepartum and
      intrapartum care, and pilot testing the Web-based version in Fall 2003 by using
      wireless, handheld technology.

PMID- 14660951
TI  - International service learning in midwifery and nursing education.
AB  - The health of women and childbearing families is a global concern that must be
      addressed if we are to be successful in ensuring healthy families. Numerous
      strategies have been suggested to increase appreciation for the global factors
      that influence maternal and child health and the overall health status of a
      community. Inclusion of cultural content in courses offered in educational
      programs and provision of clinical learning experiences in diverse communities
      have commonly been used in midwifery and nursing education. This article reviews
      the concept of service learning and its application in a course that provides an
      opportunity for students to participate in an international immersion program.
      Evaluation of the course found that participants increased their knowledge and
      skills in providing reproductive health care, developed appreciation for the
      knowledge and skills of traditional birth attendants, and expanded their world
      view of women and families in communities.

PMID- 14660952
TI  - Pearls of wisdom for clinical teaching: expert educators reflect.
AB  - A group of expert educators, each with more than 20 years of experience in
      midwifery education, was asked to contribute a "pearl (or pearls) of wisdom" for
      clinical teaching. Despite minimal instructions regarding what type of wisdom was
      being solicited, remarkable similarities emerged from the educators'
      contributions. Themes included the need for self-evaluation to become a competent
      preceptor, the role-modeling function of the preceptor, the development of
      critical thinking in students, the need to appreciate students' varying learning
      styles and individual ways of functioning, and the use of positive reinforcement.
      Although these may seem like universally accepted concepts in clinical teaching,
      one contributor related stories she heard from students about "hazing" behaviors
      that have a negative impact on learning. This points to the need for ongoing
      education about being an educator, another theme echoed in several of the
      contributions.

PMID- 14660953
TI  - Genealogic origins of nurse-midwifery education programs in the United States.
AB  - This article presents a genealogy of all known basic and refresher nurse
      midwifery education programs enabling every CNM and CM to track their individual
      lineage back to Hattie Hemschemeyer or Mary Breckinridge. Feeling connected to
      our founding foremothers increases our understanding of who we are and what our
      commitment is to the families we serve. Genealogy also gives us an opportunity to
      reflect on the early history and continuing historical trends of our education
      programs.

PMID- 14660954
TI  - A glossary of terms used in distance education.

PMID- 14660978
TI  - Where the rubber meets the road in pharmacogenetics: assessment of gene
      environment interactions.

PMID- 14660979
TI  - Volume as a surrogate for percutaneous coronary intervention quality: is this the
      right measuring stick?

PMID- 14660980
TI  - Women and outcomes of coronary artery bypass surgery: do we have an answer?

PMID- 14660981
TI  - Are some patients in Canada treated more equally than others? The Orwell
      prophecy.

PMID- 14660982
TI  - The winter's tale--and toll.

PMID- 14660983
TI  - Patients' willingness to participate in placebo-controlled trials of
      antihypertensive therapy.

PMID- 14660984
TI  - Improving quality of care in the real world: efficacy versus effectiveness?

PMID- 14660985
TI  - Association between factor V Leiden, prothrombin G20210A, and
      methylenetetrahydrofolate reductase C677T mutations and events of the arterial
      circulatory system: a meta-analysis of published studies.
AB  - BACKGROUND: The association between the inherited gene mutations of factor V,
      prothrombin, and homocysteine metabolism and venous thromboembolic events is
      accepted widely; however, their influence on the arterial circulatory system
      remains controversial. METHODS: We performed a MEDLINE search to identify
      published case-control and cohort studies correlating the factor V Leiden,
      prothrombin (PT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T
      (TT genotype) mutations with myocardial infarction, ischemic stroke, or
      peripheral vascular disease. Studies were included only when they adhered to
      specific diagnostic criteria for ischemic events and met the published
      methodological criteria. Odds ratios (ORs) with accompanying 95% CIs were
      calculated for each mutation and clinical end points with a random-effects model
      (DerSimonian and Laird method). RESULTS: The association between inherited gene
      mutations and arterial ischemic events was modest: factor V Leiden mutation (OR,
      1.21; 95% CI, 0.99-1.49), PT G20210A mutation (OR, 1.32; 95% CI, 1.03-1.69), and
      MTHFR TT mutation (OR, 1.20; 95% CI, 1.02-1.41). Subgroup analyses of younger
      patients (<55 years old) and of women revealed slightly stronger associations
      overall. CONCLUSIONS: Genetic abnormalities specific to factor V, prothrombin,and
      homocysteine metabolism increase the risk for myocardial infarction and ischemic
      stroke, particularly among younger patients and women. Because the overall
      association is only modest, screening studies should be limited to carefully
      selected patient populations. The individual propensity for arterial and venous
      thrombosis is likely influenced by differing local mechanisms, systemic
      mechanisms, or both.

PMID- 14660986
TI  - Current perspectives on reperfusion therapy for acute ST-segment elevation
      myocardial infarction: integrating pharmacologic and mechanical reperfusion
      strategies.
AB  - The therapeutic approach to patients with acute ST-segment elevation myocardial
      infarction (STEMI) has advanced rapidly over the past decade. Intravenous
      fibrinolytic therapy remains the most common form of reperfusion therapy
      worldwide, since fibrinolytics are associated with a dramatic reduction in
      mortality rates. However, primary percutaneous coronary intervention (PCI) is
      associated with improved outcomes and less bleeding complications compared with
      fibrinolytic therapy, but it is not widely available. Adjunctive therapies with
      intracoronary stents, glycoprotein (GP) IIb/IIIa inhibitors, and more potent
      antithrombin agents have shown great promise for the initial treatment of STEMI
      and have stimulated further investigation of combined pharmacological/mechanical
      reperfusion strategies that may be synergistic. Although the optimal combination
      of fibrinolytics, antiplatelet agents, antithrombins, and mechanical reperfusion
      at hospitals with and without primary PCI facilities remains elusive, results
      from recent studies suggest that such a combined approach may facilitate transfer
      of patients with STEMI from a referral hospital to an invasive hospital for
      definitive primary PCI after administration of a potent pharmacologic regimen
      designed to enhance early infarct-related artery reperfusion. Thus, as the
      reperfusion era continues to evolve, the ideal treatment strategy for patients
      with STEMI is being redefined to integrate pharmacologic and mechanical
      approaches to reperfusion.

PMID- 14660987
TI  - Electron beam CT versus helical CT scans for assessing coronary calcification:
      current utility and future directions.
AB  - BACKGROUND: Traditional risk factors for coronary artery disease predict the
      development of atherosclerosis; however, their ability to identify individual
      patients at risk of events is limited. METHODS: Coronary artery calcium (CAC) is
      a specific marker of atherosclerosis. It can be visualized and measured
      noninvasively by various imaging techniques, which may add incremental prognostic
      value to conventional coronary factors. RESULTS: The field of atherosclerosis
      imaging has expanded rapidly in the last decade, and technologies such as
      electron-beam computed tomography (EBCT) have contributed to our understanding of
      the prevalence of occult coronary artery disease and its consequences. Other
      modalities have been previously limited by the decreased temporal and spatial
      resolution and slower acquisition. Recent advances in helical CT (HCT) imaging
      with the development of multiple row detectors CT (MDCT) and improvements in the
      temporal resolution have renewed clinicians' interests in using this modality to
      evaluate CAC, although the scores obtained with MDCT may differ somewhat from
      those obtained with the EBCT technology. This study critically analyzes the
      literature comparing the utility of EBCT and HCT in detecting coronary calcium to
      identify individuals at increased risk for future coronary events. CONCLUSIONS:
      MDCT is a promising tool for coronary calcium scoring; however, more studies are
      needed comparing EBCT and MDCT, especially at lower CAC levels.

PMID- 14660988
TI  - Identification, course, and treatment of depression after admission for a cardiac
      condition: rationale and patient characteristics for the Identifying Depression
      As a Comorbid Condition (IDACC) project.
AB  - BACKGROUND: Given the prevalence of cardiovascular disease and the high rates of
      depression among cardiac patients, there is a need to develop practical ways to
      identify this population and provide pragmatic general-practitioner-based
      interventions for managing depression as a comorbid condition. METHOD: The
      Identifying Depression As a Comorbid Condition (IDACC) study employed a hybrid
      design, incorporating a randomized controlled trial nested within a prospective
      cohort study. IDACC screened for depression in patients hospitalized in South
      Australia for a range of cardiac conditions, with outcome measures monitored for
      12 months after discharge. The subgroup identified as depressed was entered into
      the nested IDACC trial, which tests the hypothesis that identifying depression
      and offering an evidence-based intervention to general practitioners,
      incorporating multidisciplinary telephone case conferencing, will reduce levels
      of depression, improve quality of life, and reduce associated economic costs.
      RESULTS: At baseline, 46.3% of 1455 participants screened were classified as
      depression cases on the basis of their score on the Center for Epidemiological
      Studies Depression Scale (> or =16) or the Hospital Anxiety and Depression Scale
      (> or =8). Elevated scores were associated with being younger, female, divorced
      or separated, not employed, living alone, having a lower level of education, and
      having poorer health and quality of life. Nearly one fifth (19.4%) of
      participants had Center for Epidemiological Studies Depression Scale scores >27,
      which is indicative of major depression. CONCLUSIONS: This project confirms, in
      an Australian setting, the high prevalence of depressive symptoms among
      hospitalized cardiac patients. Follow-up over 12 months will enhance
      understanding of the natural history of depression in cardiac patients, while the
      nested trial will inform on effectiveness of an intervention involving tailored
      advice and support to general practitioners.

PMID- 14660989
TI  - Hypertensive patients' willingness to participate in placebo-controlled trials:
      implications for recruitment efficiency.
AB  - BACKGROUND: Underenrollment and selective enrollment plague many clinical trials.
      Little is known about why hypertensive patients agree or refuse to participate in
      placebo-controlled trials (PCT) of antihypertensive drugs, whether the prospect
      of receiving placebo influences willingness to participate (WTP), or whether
      patients who participate differ from those who do not. METHODS: We described a
      hypothetical PCT of a new antihypertensive drug to 126 patients who would be
      eligible for ongoing phase III trials. We solicited patient motivations and
      concerns regarding trial participation by using open-ended questions, assessed
      the patients' stated WTP, and used logistic regression to determine patient
      characteristics associated with WTP. We reassessed WTP in 62 patients after
      revealing, in random order, that 10%, 30%, and 50% of patients would receive
      placebo. RESULTS: The most commonly cited motivations for participating included
      personal health benefits (40%), helping other patients (37%), and contributing to
      scientific knowledge (15%). The most common concerns were having to stop current
      medications (56%), inconvenience/annoyance (38%), fear of known side effects
      (35%), and the possibility of receiving placebo (24%). Overall, 47% of patients
      (95% confidence interval, 38% to 56%) were willing to participate. Younger
      patients (57% versus 37%; P =.01), nonsmokers (50% versus 24%; P =.04), and
      patients who had participated in research previously (77% versus 20%; P =.009)
      were all significantly more willing to participate. Fewer patients were willing
      to participate as the percentage who would receive placebo increased (P =.02),
      but randomly assigning fully half of patients to placebo still yielded maximal
      recruitment efficiency. CONCLUSIONS: Hypertensive patients participate in trials
      for altruistic and personal health reasons. Differences between patients who do
      or do not participate may influence trial outcomes. The proportion of patients
      receiving placebo influences some patients' enrollment decisions but is not a key
      determinant of recruitment efficiency.

PMID- 14660990
TI  - A randomized, placebo-controlled trial of early eptifibatide for non-ST-segment
      elevation acute coronary syndromes.
AB  - BACKGROUND: The acute benefits of platelet glycoprotein IIb/IIIa inhibitors for
      non-ST-segment elevation acute coronary syndromes (NSTE ACS) remain unclear.
      METHODS: In this pilot trial, 311 patients with NSTE ACS were randomly assigned
      in the emergency department to double-blinded therapy with eptifibatide or
      placebo for 12 to 24 hours before crossover to open-label eptifibatide. Serial
      creatine-kinase MB (CK-MB) and quantitative cardiac troponin T levels were
      collected during the first 24 hours to assess the impact of early platelet
      glycoprotein IIb/IIIa blockade on infarct size as measured by cardiac markers.
      RESULTS: Median peak CK-MB (10.3 vs 11.8 ng/mL; P =.71) and peak quantitative
      cardiac troponin T levels (0.2 vs 0.3 ng/mL; P =.95) were similar between
      treatment groups, respectively. Median calculated peak CK-MB values (41 vs 40
      ng/mL; P =.72) and area under the CK-MB curve measurements (980 vs 764
      microg/min/L; P =.68) from curve-fitting analyses that could be performed in 106
      of 311 patients were also similar. CONCLUSIONS: In this pilot trial, early
      administration of eptifibatide in the emergency department did not modulate
      serologic measurements of infarct size in patients with NSTE ACS.

PMID- 14660991
TI  - Global patterns of use of antithrombotic and antiplatelet therapies in patients
      with acute coronary syndromes: insights from the Global Registry of Acute
      Coronary Events (GRACE).
AB  - BACKGROUND: Many agents are available to treat acute coronary syndromes (ACS),
      yet limited information is available about their use from a multinational
      perspective. The objective of this report was to describe patterns of use of
      antithrombotic and antiplatelet therapies in patients with the spectrum of ACS
      through the use of data from the Global Registry of Acute Coronary Events
      (GRACE). METHODS: Data from 12,665 patients with ACS were analyzed. Baseline
      characteristics, clinical presentation, and medication use were compared.
      Regional differences in the administration of antiplatelet and antithrombotic
      therapies were analyzed. Multivariable logistic regression was implemented to
      determine independent variables indicating the use of various hospital therapies.
      RESULTS: Overall, unfractionated heparin was used in 57% of patients and low
      molecular-weight heparin in 47% (P <.0001). More than 90% of patients received
      aspirin, but approximately 13% were not discharged on aspirin. Overall, 30% of
      patients received thienopyridines (with percutaneous coronary intervention [PCI]
      in 79%). Of those who did not receive aspirin, 31% received thienopyridines.
      Intravenous glycoprotein inhibitors were given to 17% of patients. Among those
      treated with PCI, only 47% received glycoprotein inhibitors, and 21% of those
      given glycoprotein inhibitors did not undergo PCI. Significant geographic
      variation was apparent in the use of unfractionated heparin, low-molecular-weight
      heparin, thienopyridines, and glycoprotein inhibitors. CONCLUSIONS: Despite the
      availability of guidelines, striking geographic and practice variations are
      apparent in the use of antithrombotic and antiplatelet therapies. There remains
      significant room for improvement in the use of these therapies in patients with
      ACS, which should lead to improvement in care and outcomes.

PMID- 14660992
TI  - The cholesteryl ester transfer protein Taq1B gene polymorphism predicts clinical
      benefit of statin therapy in patients with significant coronary artery disease.
AB  - BACKGROUND: Cholesteryl ester transfer protein (CETP) regulates plasma lipid
      distribution. A polymorphism in the CETP gene (Taq1B) is associated with CETP
      activity, HDL concentration, atherosclerosis progression, and response to
      statins, and may influence cardiovascular (CV) events. We studied CETP Taq1B
      genotype, plasma HDL, and clinical events among all patients and patients
      stratified by statin treatment. METHODS: Consenting patients (n = 2531) with
      significant coronary artery disease (> or =1 lesion of > or =70% stenosis)
      undergoing coronary arteriography were genotyped, grouped by statin prescription
      at hospital discharge, and prospectively followed-up for the outcomes of all
      cause mortality and myocardial infarction. RESULTS: CETP Taq1B genotype
      frequencies were: B1B1, 32.9%; B1B2, 50.3%; and B2B2 16.8%. Plasma HDL was
      reduced for B1B1 patients (33 +/- 12 mg/dL, vs 36 +/- 13 mg/dL and 36 +/- 13
      mg/dL for B1B2 and B2B2, respectively, P for trend =.003). Overall, event rates
      did not differ between genotypes. Event rates were similar among untreated
      (24.8%) and statin-treated (24.2%) B1 homozygotes (P = NS); statins significantly
      reduced events for B1B2 subjects (28.0% vs 21.0%, P =.009) and for B2B2 subjects
      (26.4% vs 17.4%, P =.048). Therapeutic benefit for B2 carriers remained after
      adjustment for covariates, and regression interaction analysis showed that B2
      carriers experienced reduced events (relative risk [RR] 0.62, 95% CI 0.45-0.86),
      but statins did not benefit those with B1B1 (RR 1.09, 95% CI 0.70-1.7; P for
      interaction =.02). Findings were similar for the end point of death alone,
      although a modest benefit was seen in B1B1 patients (RR 0.67, P =.10), in
      addition to the strong benefit for B1B2 (RR 0.53, P =.001) and B2B2 (RR 0.28, P
      =.001). CONCLUSIONS: The CETP Taq1B polymorphism is associated with differential
      HDL levels but no significant differential in CV risk in the absence of
      treatment. Importantly, however, CV event reduction by statin therapy is
      substantially enhanced in the presence of a B2 allele. Our findings suggest, for
      the first time, the potential of CETP Taq1B genotyping to enable more effective,
      pharmacogenetically directed therapy.

PMID- 14660993
TI  - Anginal symptoms consistently predict total mortality among outpatients with
      coronary artery disease.
AB  - BACKGROUND: Age, race, education, and diabetes have been associated with
      differences in anginal symptoms, treatments, and outcomes among outpatients with
      coronary artery disease (CAD), but there is little data on whether such
      characteristics affect relationships between anginal symptoms and mortality.
      METHODS: Using a prospective cohort design, we examined associations of anginal
      symptoms, as assessed by the Seattle Angina Questionnaire, with total mortality
      among 8908 outpatients with CAD to investigate whether this relationship is
      influenced by patient demographic or clinical characteristics. Potential effect
      modification was primarily assessed for age, race, education, and diabetes, and
      secondarily assessed for smoking, prevalent congestive heart failure (CHF),
      myocardial infarction, and coronary revascularization. RESULTS: Over 2 years mean
      follow-up, there were 896 deaths. After adjustment for potential confounders,
      persons reporting greater physical limitation due to angina had higher mortality:
      27% higher with mild limitation (hazard ratio [HR] 1.27, 95% CI 0.98-1.64), 61%
      higher with moderate limitation (HR 1.61, 95% CI 1.27-2.05), and 2.5-fold higher
      with the greatest limitation (HR 2.55, 95% CI 1.97-3.30), compared with little or
      no limitation (P for trend <.001). Anginal instability was also independently
      predictive of mortality. There was little evidence that these relationships
      varied by age, race, education, diabetes, smoking, or presence of CHF, prior
      myocardial infarction, or prior coronary revascularization (P for each
      interaction >.28). Anginal symptoms predicted higher mortality risk comparable to
      a decade of age difference, presence of diabetes, or presence of CHF.
      CONCLUSIONS: Among outpatients with CAD, self-reported anginal symptoms
      consistently predict mortality irrespective of differences in age, race,
      education, or clinical comorbidities.

PMID- 14660994
TI  - Comparison of treatment and outcomes for patients with acute myocardial
      infarction in Minneapolis/St. Paul, Minnesota, and Goteborg, Sweden.
AB  - BACKGROUND: Treatment of acute myocardial infarction (AMI) is changing, and
      differences in medical practice are observed within and between countries on the
      basis of local practice patterns and available technology. These differing
      approaches provide an opportunity to evaluate medical practice and outcomes at
      the population level. The primary aim of this study was to compare medical care
      in patients hospitalized with AMI in 2 large cities in Sweden and the United
      States. A secondary aim was to compare medical outcomes. METHODS: All resident
      patients (age range, 30-74 years) hospitalized with AMI in Goteborg, Sweden (1995
      1996), and a representative population-based sample of all patients with AMI in
      Minneapolis/St. Paul, Minn (1995). RESULTS: Patients with AMI in Goteborg (GB)
      were older than patients in Minneapolis/St. Paul (MSP), but fewer patients in GB
      had a prior history of cardiovascular disease. During the AMI admission, coronary
      angiography, percutaneous coronary angioplasty (PTCA), and coronary artery bypass
      grafting (CABG) were performed twice as frequently in MSP than in GB.
      Echocardiogram and exercise testing were more frequently performed in GB. During
      hospitalization, beta-blockers were more frequently prescribed in GB, whereas
      calcium channel blockers, long- and short-acting nitrates, intravenous
      nitroglycerine, digitalis, aspirin, oral anticoagulants, heparin, and lidocaine
      were significantly more common in MSP. Thrombolysis, acute PTCA, ACE inhibitors,
      and diuretics were similar. Reinfarction was higher in men in GB (4% vs 1%, P
      <.009) and women in GB (3% vs 1%, P = not significant). On discharge, beta
      blockers and diuretics were prescribed significantly more often in GB, whereas
      calcium channel blockers, nitrates, and digitalis were prescribed more often in
      MSP. Aspirin and ACE inhibitors had similar usage rates. Despite these diagnostic
      and treatment contrasts, there were no differences in mortality rate at 30 days
      or after 3 years of follow-up after risk-adjusting for patient baseline
      differences. CONCLUSION: Comparing patients hospitalized with AMI in MSP and GB,
      we found marked differences in medical care, with invasive strategies more likely
      to be used in MSP. This may be the result of historical practice patterns, the
      healthcare system, and healthcare financing differences. Despite these
      differences, short- or long-term mortality rates were identical.

PMID- 14660995
TI  - Universal health insurance coverage does not eliminate inequities in access to
      cardiac procedures after acute myocardial infarction.
AB  - BACKGROUND: It remains unclear whether socioeconomic status (SES) influences
      access to invasive cardiac procedures after acute myocardial infarction (AMI) in
      a universal health care system. The objective of this study was to evaluate the
      effect of SES on access to cardiac procedure after AMI in a universal health care
      system. METHODS: This was an observational cohort study of all patients with a
      first AMI in the province of Quebec, Canada, between 1985 to 1995. Information on
      treatment was obtained from the discharge and physicians' claims databases. SES
      was obtained from census data by linking postal codes. SES-independent predictors
      of use were identified, then incorporated in hierarchical models to predict use
      in low, medium, and high SES areas. The main outcome measures were rates of
      cardiac catheterization, percutaneous coronary intervention (PCI), and coronary
      artery bypass graft surgery (CABG) as a function of SES. RESULTS: SES data were
      available for 62,364 individuals with a first AMI. Of these, 65% were men and the
      mean age was 64 +/- 13 years. Rates of cardiac procedures rose with an increase
      in several SES measures. After adjustment for individual-level predictors of use
      of cardiac catheterization, average rent, (odds ratio per $100 difference: 1.57,
      95% credible interval: 1.36 to 1.80) and proportion of renters, (odds ratio, 2.2;
      95% CI: 1.21 to 3.73) in the area were independent SES predictors. Patients in
      low SES areas (median family income: $ 30,809 CDN) were less likely to undergo
      cardiac catheterization than patients in high SES areas ($92,169 CDN) (men: 33%;
      compared with 47%; women: 18%; compared with 47%). However, among patients with
      cardiac catheterization, SES was not associated with the use of revascularization
      procedures. For example, PCI rates for men within 90 days after AMI were 26%,
      compared with 25% in low and high SES areas, respectively. CABG rates were 15%,
      compared with 19%. CONCLUSIONS: We found that in the universal health care system
      of Canada, access to cardiac catheterization after AMI varied according to SES.
      Among those with cardiac catheterization, SES did not appear to influence further
      use of revascularization procedures.

PMID- 14660996
TI  - Comparison of health-related quality-of-life outcomes of men and women after
      coronary artery bypass surgery through 1 year: findings from the POST CABG
      Biobehavioral Study.
AB  - BACKGROUND: Women undergoing coronary artery bypass graft (CABG) surgery have a
      worse medical condition and fewer social and financial resources than men. Some
      studies have found that women recover less well than men after CABG, whereas
      others have found women's outcomes comparable to those of men. Past studies of
      health-related quality of life after CABG have too few women for adequate
      comparison with men and have not included patients whose data are not available
      at baseline (eg, emergency CABG), limiting generalizability. METHODS: A
      longitudinal study of symptoms and health-related quality of life was conducted
      among patients from four clinical centers enrolling both men (n = 405) and women
      (n = 269) in the Post CABG Biobehavioral Study in the United States and Canada.
      RESULTS: After 6 weeks from CABG (average 81 days), both men and women had less
      anxiety and symptoms related to depression than before surgery (P <.001). After 6
      months (average 294 days), both men and women improved in physical and social
      functioning (P <.001). Although changes in scale scores were similar for men and
      women at each time point, women scored lower than men on these domains (P <.001,
      adjusted for baseline medical and sociodemographic differences) and had more
      symptoms related to depression through 1 year after CABG (P =.003). CONCLUSIONS:
      Both male and female patients improve in physical, social, and emotional
      functioning after CABG, and recovery over time is similar in men and women.
      However, women's health-related quality-of-life scale scores remained less
      favorable than men's through 1 year after surgery.

PMID- 14660997
TI  - Quality of care for secondary prevention for patients with coronary heart
      disease: results of the Hastening the Effective Application of Research through
      Technology (HEART) trial.
AB  - BACKGROUND: Effective therapies for reducing mortality rates in persons with
      coronary heart disease (CHD) remain underused. We report the results of an
      effectiveness trial of a quality improvement effort to increase the use of 3
      hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, beta-blockers,
      and angiotensin-converting enzyme (ACE) inhibitors in patients with CHD in a
      network-model managed-care setting. METHODS: Patients with CHD were identified by
      searching a claims database. The use of therapies was assessed by linkage with a
      pharmacy database. An intervention, consisting of a guideline summary, peer
      comparison performance feedback, and patient specific chart reminders was
      evaluated in a randomized, practice-based effectiveness trial. RESULTS: Data were
      available for >700 patients per year (1999-2002) in 131 practices. At baseline
      (1999), 55% of patients were receiving HMG CoA reductase inhibitors, 39% of
      patients were receiving beta-blockers, and 24% of patients were receiving ACE
      inhibitors. The use of all 3 types of medications increased steadily with time,
      with the exception of a decrease in the use of HMG CoA reductase inhibitors in
      the final year (2002). No difference in medication use was observed between
      randomized groups. CONCLUSIONS: The observed pattern of care supports the
      contention that the quality of outpatient care for secondary prevention of CHD
      improved from 1999 to 2002 in this setting. The basis for the inconsistent
      pattern of use of HMG CoA reductase inhibitors is not certain, but may relate to
      concerns about toxicity. Centralized mailings of guideline summaries, performance
      feedback reports, and chart reminders had no observable impact on quality of care
      in this setting. More intensive intervention may be required to improve the
      quality of outpatient care for the secondary prevention of CHD.

PMID- 14660998
TI  - Risk determination of dyslipidemia in populations characterized by low levels of
      high-density lipoprotein cholesterol.
AB  - BACKGROUND: Current guidelines for managing dyslipidemia qualify patients for
      treatment based on low-density lipoprotein cholesterol (LDL-C) levels and other
      risk factors for coronary heart disease (CHD). However, when LDL-C is the sole
      lipid criterion for initiating therapy, patients with levels below the treatment
      initiation threshold who are at high risk because of low levels (<40 mg/dL) of
      high-density lipoprotein cholesterol (HDL-C) might not be identified. Twenty
      percent of male patients with CHD in the United States fall into this category.
      The total cholesterol/HDL-C (TC/HDL-C) ratio predicts CHD risk regardless of the
      absolute LDL-C and HDL-C. METHODS: We compared guidelines based on TC/HDL-C and
      LDL-C with those recommended by the National Cholesterol Education Program Adult
      Treatment Panel III (ATP III). Both sets of guidelines were applied to 9837
      adults (>20 years of age) in the Turkish Heart Study, which has shown that 75% of
      men and 50% of women in Turkey have HDL-C <40 mg/dL. RESULTS: ATP III guidelines
      identified 14% of Turkish adults, 20 years or older, as candidates for lifestyle
      treatment only and an additional 18% for drug treatment. In conjunction with ATP
      III LDL-C thresholds, the TC/HDL-C ratio (>3.5, patients with CHD; > or =6.0, 2+
      risk factors, > or =7.0, 0 to 1 risk factor) assigned lifestyle therapy alone to
      18% and drug treatment to an additional 36%. Among primary prevention subjects at
      high risk because of age (men > or =45 years; women > or =55 years), both sets of
      guidelines prescribed lifestyle therapy for only 5%; however, drug treatment was
      recommended for an additional 13% by ATP III guidelines and an additional 18% by
      TC/HDL-C and LDL-C. CONCLUSIONS: In populations at risk for CHD caused by low HDL
      C, qualification of subjects for treatment based on either the TC/HDL-C ratio or
      LDL-C thresholds identifies more high-risk subjects for treatment than LDL-C
      threshold values alone, and use of the ratio, instead of risk tables, simplifies
      the approach for physicians.

PMID- 14660999
TI  - Annual distribution of ventricular tachycardias and ventricular fibrillation.
AB  - BACKGROUND: Ischemic events and coronary deaths show seasonal variability with a
      peak during December and January. It remains unclear whether ventricular
      tachycardias (VT) and ventricular fibrillation (VF) follow a similar pattern. The
      purpose of this study was to investigate the annual distribution of malignant
      ventricular arrhythmias. METHODS: Over a period of 11 years, all appropriate
      shock episodes (SE) after VT and VF in patients with an implantable cardioverter
      defibrillator (lCD) were analyzed with respect to the month of occurrence. An
      appropriate SE was defined as out-of-hospital VT/VF terminated by lCD shocks.
      Multiple shocks within 1 week were defined as 1 SE. RESULTS: Two hundred and
      thirty-three of 308 patients with an lCD had appropriate SE during follow-up. In
      these patients the seasonal variation of 753 SE was calculated. Most SE occurred
      during January (93 SE), and the fewest SE occurred during June (39 SE). The
      seasonal pattern was statistically significant with a peak during winter (P
      =.001). The seasonal pattern did not differ between patients with an ischemic and
      those with a nonischemic underlying cardiac disease. CONCLUSION: Appropriate
      shock episodes due to out-of-hospital VT/VF in patients with an lCD show seasonal
      variation with a significant peak during winter. The pattern is similar in
      patients with ischemic and nonischemic cardiac disease.

PMID- 14661000
TI  - Worldwide evaluation of a defibrillation lead with a small geometric electrode
      surface for high-impedance pacing.
AB  - BACKGROUND: Pacing leads with a small electrode surface for high-impedance
      stimulation have been shown to prolong pacemaker longevity, but no sufficient
      data is available on the safety and feasibility of a defibrillation lead with
      this novel design. METHODS: We evaluated the clinical performance of a tined,
      steroid-eluting defibrillation lead with a small electrode surface area (model
      6944) in a prospective multicenter study. A total of 542 patients with
      conventional indications for an implantable cardioverter defibrillator were
      randomized 1:1 to receive either the model 6944 or a tined, steroid-eluting
      defibrillation lead with a conventional sized electrode surface area (model
      6942). Device performance and electrical parameters were evaluated at implant and
      1, 3, 6, and 12 months thereafter (mean follow-up 11.3 +/- 5.6 months). RESULTS:
      Baseline characteristics, lead implant success rates, and defibrillation
      thresholds did not differ significantly between the 2 groups. While pacing
      thresholds did not differ significantly during follow-up, pacing impedance was
      approximately twice as high in the model 6944 as in the model 6942 lead (P
      <.0001). Mean R-wave amplitudes were smaller in patients with a 6944 (9.1 +/- 3.1
      mV vs 9.8 +/- 3.6 mV for model 6942, P <.05), but remained stable within both
      groups throughout the observation period. The total number of ventricular lead
      related adverse events and patient survival did not differ significantly between
      the 2 groups. CONCLUSIONS: The use of a defibrillation lead with a small
      electrode surface for high-efficiency pacing is safe and feasible and increases
      pacing impedance without significantly compromising clinical performance.

PMID- 14661001
TI  - Analysis of the institutional volume-outcome relations for balloon angioplasty
      and stenting in the stent era in California.
AB  - BACKGROUND: Coronary artery stenting has become the predominant form of
      percutaneous coronary intervention. However, it is not clear whether a better
      outcome is conferred by stent placement in high-volume, more experienced centers
      as has been shown with balloon angioplasty. Furthermore, as stent procedures
      become more common, balloon angioplasty becomes less frequent. Thus, we
      separately analyzed the outcomes after coronary angioplasty and stenting in a
      large, unselected population to determine the effect of annual institutional
      angioplasty or stent volume on in-hospital outcomes after balloon angioplasty or
      stenting. METHODS: The California Office of Statewide Health Planning and
      Development database was queried to obtain discharge data on all patients in 1997
      treated with percutaneous transluminal coronary angioplasty (PTCA) or a stent
      procedure. Hospitals were divided into low-volume (<200 procedures), intermediate
      volume (200 to 400 procedures), and high-volume (>400 procedures) institutions as
      a function of their 1997 PTCA or stent volumes to assess the effect of volume on
      outcome. RESULTS: There were 44,276 percutaneous revascularization procedures
      performed in California in 1997, of which 57% involved coronary stent placement.
      Mortality rates after PTCA were 2.6%, 1.9%, and 1.4% in low-, intermediate- and
      high-volume PTCA hospitals, respectively (P <.001). The need for same-day
      coronary artery bypass grafting (CABG) after PTCA was 2.4%, 2.1%, and 1.2% in low
      , intermediate- and high-volume PTCA hospitals, respectively (P <.001). Mortality
      rates after stent placement were 1.6%, 1.5%, and 1.1% in low-, intermediate-, and
      high-volume stent hospitals, respectively (P =.022). The need for same-day CABG
      after stent placement was 1.1%, 1.2%, and 0.8% in low-, intermediate-, and high
      volume stent hospitals, respectively (P =.014). CONCLUSIONS: Short-term results
      of balloon angioplasty and stent procedures are improved when performed in high
      volume hospitals.

PMID- 14661002
TI  - Restenosis in Intervened Coronaries with Hyperhomocysteinemia (RICH).
AB  - BACKGROUND: Controversy exists regarding the contribution made by elevated serum
      homocysteine evels in raising the risk of restenosis after percutaneous coronary
      interventions. The objective of this study was to determine whether elevated
      homocysteine evels increase the risk of restenosis. METHODS: Two hundred and two
      consecutive patients undergoing percutaneous coronary intervention with stents on
      previously nonintervened native coronary arteries were eligible for enrollment in
      the study. Before the percutaneous coronary intervention, a fasting serum
      homocysteine evel was drawn. Patients were followed-up by their primary
      cardiologists for recurrence of symptoms. Those patients who had a recurrence of
      anginal symptoms consistent with clinical restenosis were referred for a repeat
      angiogram. All other patients were followed-up medically. The homocysteine evels
      of the patients who had repeat angiography for recurrent symptoms were compared
      to those who were followed-up medically. RESULTS: Age, stent ength, stent
      diameter, and homocysteine evels were all associated with an increased risk of
      restenosis in the univariate analysis. In the multiple ogistic regression model,
      the only variable that remained significant in relation to an increased risk of
      restenosis was homocysteine. There was a significant difference in the mean
      homocysteine evels between the restenosis group (13.7 micromol/L) and those
      without restenosis (9.6 micromol/L; P <.0001). A homocysteine evel > or =11.1
      micromol/L was identified as the best threshold for an increased risk of
      restenosis with a sensitivity of 75.0% and specificity of 76.9% (OR 6.5, CI 2.3
      18.6; P =.0004). CONCLUSION: This study demonstrates that elevated homocysteine
      evels strongly correlate with an increased risk of restenosis.

PMID- 14661003
TI  - Serologic markers of persistent Chlamydia pneumonia infection and long-term
      prognosis after successful coronary stenting.
AB  - BACKGROUND: Previous studies have shown an incremental role of inflammation in
      late prognosis following coronary stenting (CS). In particular, high
      preprocedural levels of plasma C-reactive protein (CRP) have been related to
      increased hazard of late ischemic complications. Persistent Chlamydia pneumoniae
      (Cp) infection, detected by positive IgA anti-Cp titers, may be associated with
      this inflammatory process and portend a high risk of late adverse prognosis after
      CS. METHODS: A total of 483 consecutive patients with either stable or unstable
      coronary syndromes were followed-up for 1 year after successful CS. The composite
      of cardiac death, myocardial infarction, rehospitalization for rest-unstable
      angina, and exertional angina, whichever occurred first, was the clinical end
      point. Additionally, the rate of in-stent restenosis and progression of coronary
      artery disease during this period were evaluated. Anti-Cp titers and plasma CRP
      levels were measured before the procedure. RESULTS: Positive immunoglobulin A
      (IgA), but not positive immunoglobulin G (IgG), titers were significantly
      associated with high plasma CRP levels in patients with unstable coronary
      syndromes (P =.005), but not in those with stable angina (P =.7). Moreover,
      positive IgA titers were significantly related to increased risk of both the
      composite clinical end point (P =.04) and progression of coronary artery disease
      (P <.001) in patients with unstable coronary syndromes but not in those with
      stable angina. Neither positive IgA nor positive IgG titers were associated with
      the rate of in-stent restenosis. CONCLUSIONS: Persistent Cp infection may drive
      an inflammatory response in the coronary vasculature and portends an adverse late
      outcome after CS in patients with unstable coronary syndromes.

PMID- 14661004
TI  - Addition of right-sided and posterior precordial leads during stress testing.
AB  - BACKGROUND: Exercise treadmill testing has limited sensitivity for the detection
      of coronary artery disease, frequently requiring the addition of imaging
      modalities to enhance the predictive value of the test. Recently, there has been
      interest in using nonstandard electrocardiographic (ECG) leads during exercise
      testing. METHODS: We consecutively enrolled all patients undergoing exercise
      myocardial imaging with four additional leads recorded (V4R, V7, V8, and V9). The
      test characteristics of the 12-lead, the 15-lead (12-lead, V7, V8, V9), and the
      16-lead (12-lead, V4R, V7, V8, V9) ECGs were compared with stress imaging in all
      patients. In the subset of patients who underwent angiography within 60 days of
      stress testing, these lead arrays were compared with the catheterization
      findings. RESULTS: There were 727 subjects who met entry criteria. The mean age
      was 58.5 +/- 12.3 years, and 366 (50.3%) were women. Pretest probability for
      disease was high in 241 (33.1%), intermediate in 347 (47.7%), and low in 139
      (19.1%). A total of 166 subjects had an abnormal 12-lead ECG during exercise. The
      addition of 3 posterior leads to the standard 12-lead ECG resulted in 7
      additional subjects having an abnormal electrocardiographic response to exercise.
      The addition of V4R resulted in only 1 additional patient having an abnormal ECG
      during exercise. The sensitivity of the ECG for detecting ischemia as determined
      by stress imaging was 36.6%, 39.2%, and 40.0% (P = NS) for the 12-lead, 15-lead,
      and 16-lead ECGs, respectively. In those with catheterization data (n = 123), the
      sensitivity for determining obstructive coronary artery disease was 43.5%, 45.2%,
      and 45.2% (P = NS) for the 12-lead, 15-lead, and 16-lead ECGs, respectively. The
      sensitivity of imaging modalities was 77.4% when compared with catheterization.
      CONCLUSIONS: In patients undergoing stress imaging studies, the addition of right
      sided and posterior leads did not significantly increase the sensitivity of the
      ECG for the detection of myocardial ischemia. Additional leads should not be used
      to replace imaging modalities for the detection of coronary artery disease.

PMID- 14661005
TI  - Clinical profile of Streptococcus agalactiae native valve endocarditis.
AB  - BACKGROUND: Streptococcus agalactiae is an unusual pathogen in adults who are not
      pregnant. S agalactiae endocarditis is a poorly defined entity because it is
      uncommon; in contrast to other streptococcal endocarditis, it bears a high
      mortality rate. The aim of this study was to define its clinical, prognostic, and
      therapeutic profile on the basis of a series of 9 consecutive patients. METHODS:
      We conducted a prospective and multicenter study of patients with infectious
      endocarditis in which 310 episodes were included. RESULTS: S agalactiae grew in 9
      patients (3%) who had no valve prosthesis. All patients except 1 had underlying
      diseases, and all patients had serious complications; the most common
      complications were major emboli, heart failure, and shock. The valve affected was
      the mitral valve in 4 patients, the aortic valve in 2 patients, both the mitral
      and aortic valves in 2 patients, and the tricuspid valve in 1 patient. All
      episodes were on native valves. Vegetations tended to be large (maximal diameter
      >10 mm in all patients), very mobile, and pedunculated. An abscess was found in 2
      patients, and a perforation of the valve developed in 3 patients. Five patients
      died (mortality rate, 56%), 3 of whom had received antibiotic therapy alone. The
      4 patients who survived underwent combined medical-surgical therapy. CONCLUSION:
      S agalactiae native valve endocarditis is very aggressive, and early surgery
      should be considered to prevent the destruction of valves and development of
      serious complications.

PMID- 14661006
TI  - C-reactive protein elevation independently influences the procedural success of
      percutaneous balloon mitral valve commissurotomy.
AB  - BACKGROUND: Markers of systemic inflammation including C-reactive protein (CRP)
      appear to predict morbidity and mortality in various clinical conditions. The
      presence of systemic inflammation and its impact on the procedural success of
      percutaneous balloon mitral valve commissurotomy (PBMC) in patients with
      rheumatic mitral stenosis has not been previously demonstrated. METHODS:
      Measurements of CRP with a high-sensitivity assay were performed at the time of
      PBMC or during post-procedural follow-up in 119 patients with mitral stenosis of
      rheumatic morphology. Patients were questioned to exclude confounders of CRP
      elevation and categorized into undetectable (< or =0.10 mg/L) and detectable
      (>0.10 mg/L) CRP levels. Detectable levels were further classified into assay
      range (>0.10 and < or =6.0 mg/L) and elevated (>6.0 mg/L). RESULTS: CRP was
      detectable in 76% of patients and elevated (>6.0 mg/L) in 36% of patients
      studied. Procedural success occurred in 89% of patients with undetectable CRP, as
      compared with only 67% in patients with detectable CRP (P =.028). This effect
      remained after controlling for age and valve score (previously described
      predictors of PBMC success). CONCLUSIONS: Systemic inflammation is common in
      patients with rheumatic mitral valve stenosis, and the relationship between
      procedural success and CRP suggests persistent inflammation may affect the
      results of PBMC.

PMID- 14661007
TI  - Left ventricular wall stress as a direct correlate of cardiomyocyte apoptosis in
      patients with severe dilated cardiomyopathy.
AB  - BACKGROUND: Apoptosis has been implicated as a possible mechanism in the
      development of heart failure (HF), but the mechanisms involved remain unclear. In
      patients with severe dilated cardiomyopathy, we evaluated cardiomyocyte apoptosis
      in relation to the transmural distribution of Bax and Bcl-2 proteins (2 molecules
      inhibiting or promoting apoptosis, respectively) and left ventricular wall
      stresses. METHODS: We studied the presence and distribution of cardiomyocyte
      apoptosis in 90 tissue samples obtained from 8 patients who were undergoing left
      ventricular reduction with the Batista (ventricular remodeling) operation.
      Apoptosis was assessed in tissue samples taken from the entire left ventricular
      thickness (subdivided in subepicardial, midmyocardial, and subendocardial
      sections) with the terminal deoxynucleotidyl transferase mediated dUTP-biotin
      nick-end labeling (TUNEL) technique and DNA agarose gel electrophoresis. The
      expression of Bcl-2 and Bax proteins were determined with both Western analysis
      and immunohistochemistry. RESULTS: TUNEL-positive cells (apoptotic index) were
      2.3% +/- 1.4%. Apoptotic cells were predominantly distributed in the
      subendocardium, where higher levels of Bax protein were detected. The ratio of
      Bax to Bcl-2 proteins (Bax/Bcl-2) was similar in the midmyocardium or
      subepicardium, but increased in the subendocardium, where it was directly related
      to systolic wall stress (y = 0.009x - 0.629; r2 = 0.85, P <.001). The apoptotic
      index was also directly related to systolic and end-diastolic stresses calculated
      from hemodynamic and echocardiographic data (r2 = 0.77, P <.001 and r2 = 0.40, P
      <.01, respectively). CONCLUSIONS: In patients with dilated cardiomyopathy, in
      whom cardiomyocyte apoptosis is an important cause of cell loss, apoptosis is
      more extensively localized in the subendocardium and strictly related to
      ventricular wall stresses and the Bax/Bcl-2 ratio.

PMID- 14661008
TI  - Impact of infarct size on clinical and echocardiographic outcome in patients
      undergoing nonsurgical septal reduction therapy.
AB  - BACKGROUND: Nonsurgical septal reduction therapy (NSRT) with ethanol improves
      clinical and hemodynamic parameters in patients with symptomatic hypertrophic
      obstructive cardiomyopathy. The purpose of this study was to examine the impact
      of infarct size induced by ethanol injection on clinical and echocardiographic
      outcome after the procedure. METHODS AND RESULTS: The first 261 consecutive
      patients were included. The mean age was 51 +/- 6 years, and 127 patients were
      women. The mean creatine kinase (CK) after NSRT was 1411 +/- 653 units. Men had
      larger infarcts than women (P =.0028). Injecting ethanol as a bolus (P <.001),
      injecting >1 septal branch (P <.001), or injecting >3 cc of ethanol per septal
      branch (P <.001) were all determinants of infarct size. When the patients were
      divided into 4 groups according to peak CK, the New York Heart Association
      dyspnea score after NRST, the septal thickness, and left ventricular outflow
      tract gradient were more significantly reduced in patients with peak CK >1000
      U/dL compared to those with peak CK <1000 U/dL. Patients with peak CK >1500 U/dL
      had a significant drop in left ventricular ejection fraction at 6 weeks (70 +/- 6
      vs 63 +/- 6, P =.035). CONCLUSION: An average size infarct (peak CK 1000-1500
      U/dL) seems to lead to the optimal outcome after NSRT.

PMID- 14661010
TI  - Increased levels of pregnancy-associated plasma protein-A in patients with
      hypercholesterolemia: the effect of atorvastatin treatment.
AB  - BACKGROUND: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have
      recently been linked to plaque instability and are increased in acute coronary
      syndromes. The relation between PAPP-A levels and coronary risk factors, namely
      blood lipids, has not been studied to date. We have therefore investigated
      whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic
      subjects and whether PAPP-A levels are influenced by atorvastatin therapy.
      METHODS: We examined 27 subjects with isolated hypercholesterolemia free of
      manifest vascular disease and 29 age-matched healthy control subjects. Patients
      were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d).
      RESULTS: In untreated hypercholesterolemic subjects, PAPP-A levels were
      significantly higher than in control subjects (8.02 +/- 1.86 mU/L vs 6.50 +/-
      2.54 mU/L, P =.018). There was no correlation between PAPP-A levels and serum
      lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and
      40%, respectively. Despite this profound lipid lowering, there was no significant
      change in the serum PAPP-A levels. CONCLUSIONS: PAPP-A levels are elevated in
      hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A
      may therefore not only reflect plaque instability but also serve as a marker of
      total atherosclerotic burden in asymptomatic subjects with hyperlipidemia.
      However, PAPP-A levels are not influenced by atorvastatin treatment.

PMID- 14661009
TI  - Effects of low-dose angiotensin II receptor blocker candesartan on cardiovascular
      events in patients with coronary artery disease.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of
      angiotensin II receptor blockers on the prevention of cardiovascular events in
      patients with coronary artery disease (CAD). BACKGROUND: Angiotensin II may
      contribute to the pathogenesis of CAD. Long-term clinical trials have shown that
      blockade of the renin-angiotensin system can reduce cardiovascular events in
      patients with acute myocardial infarction complicated by heart failure. METHODS:
      Patients with a history of coronary intervention and no significant coronary
      stenosis on follow-up angiography 6 months after intervention were randomly
      assigned into a candesartan group (n = 203; baseline treatment plus candesartan 4
      mg/d) or a control group (n = 203; baseline treatment alone). The primary end
      point was a composite of revascularization, nonfatal myocardial infarction, or
      cardiovascular death. The secondary end point was hospitalization for
      cardiovascular causes. RESULTS: There were no changes in blood pressure and in
      other coronary risk factors in either group during a mean follow-up of 24 months.
      Primary end point risk was significantly lower in the candesartan group (n = 12)
      than in control group patients (n = 25) (P =.03). Candesartan treatment reduced
      primary end point risk (5.9% vs 12.3% for control subjects; relative risk, 0.47;
      95% CI, 0.24 to 0.93). The incidence of all events including secondary end points
      and noncardiovascular death was significantly lower in the candesartan group than
      in control group patients (23 vs 40 cases) (P =.02). CONCLUSIONS: Relatively low
      dose candesartan, which did not alter blood pressure levels, reduces
      cardiovascular risk in high-risk patients with CAD.

PMID- 14661011
TI  - Early reperfusion and late clinical outcomes in patients presenting with acute
      myocardial infarction randomly assigned to primary percutaneous coronary
      intervention or streptokinase.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) has become an
      alternative to thrombolytic therapy as a reperfusion strategy for ST-elevation
      acute myocardial infarction (AMI). METHODS: The main goal of this study was to
      determine whether PCI and thrombolytic therapy achieve comparable reperfusion
      rates, as evidenced by ST-segment resolution. Secondary end points included
      infarct vessel patency rates before hospital discharge and short- and long-term
      outcomes. Patients with ischemic chest pain with duration < or =12 hours and no
      contraindication for thrombolytic therapy were included. RESULTS: Between October
      1993 and August 1995, 58 patients were randomly assigned to streptokinase (SK)
      and 54 patients to primary PCI. Baseline clinical characteristics and infarct
      location were well balanced in both groups. Median age (interquartile range) was
      68 (58, 75) years, 29% were women, and 78% of the patients met at least one
      criterion for "not low risk" AMI (anterior location, age >70 years old, previous
      MI, systolic blood pressure <100 mm Hg, and/or heart rate >100 bpm). The median
      time from symptom onset to random assignment was 217 (139, 335) minutes in the
      PCI group and 210 (145, 334) minutes in the SK group. Median random assignment to
      balloon time was 82 (55, 100) minutes, and median random assignment to needle
      time was 15 (10, 26) minutes (P <.0001). TIMI grade 3 flow after primary PCI was
      obtained in 85% of patients. The proportion of patients with ST-segment
      resolution > or =50% at 120 minutes was 80% in the PCI group and 50% in the SK
      group (P =.001). The predischarge angiogram showed the presence of TIMI 3 flow in
      96% of patients who received PCI and 65% of patients who received SK (P <.001). A
      composite of in-hospital death, reinfarction, severe heart failure, stroke, and
      major bleeding occurred in 15% of patients who received PCI and 21% of patients
      who received SK (P =.4). At 3 years, freedom from the composite end point of AMI,
      postdischarge revascularization, and death was 61% in the PCI group and 40% in
      the SK group (P =.025). CONCLUSIONS: Our study shows that primary PCI, as
      compared with SK, is associated with more effective ST-segment resolution, higher
      patency rates in the infarct vessel at 7 days, and more favorable clinical
      outcomes at 3 years of follow-up.

PMID- 14661013
TI  - Therapeutic strategy in atrial fibrillation.

PMID- 14661012
TI  - Acetylcysteine in the prevention of contrast-induced nephropathy after coronary
      angiography.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) after coronary angiography is
      associated with increased morbidity and mortality rates. Preliminary studies with
      N-acetylcysteine (NAC) have found conflicting results in the prevention of CIN in
      patients undergoing coronary angiography. This study was designed to evaluate the
      efficacy and safety of NAC in the prevention of CIN in patients undergoing
      coronary angiography. METHODS: This study was prospective, randomized, double
      blind, and placebo-controlled. Patients referred for elective coronary
      angiography with a baseline creatinine clearance level <50 mL/min and serum
      creatinine >1.2 mg/dL were randomly assigned to 1500 mg NAC or placebo, starting
      the evening before angiography and given every 12 hours for 4 doses. The primary
      study end point was the development of CIN, which was defined as an increase of
      >0.5 mg/dL or an increase of > or =25% in serum creatinine over baseline within
      48 hours of angiography. Secondary end points included changes in serum
      creatinine and blood urea nitrogen, requirement of dialysis, side effects of
      study medication, hospital length of stay, and hospital charges. RESULTS: CIN
      occurred in 8.2% (4/49) of patients taking NAC and 6.4% (3/47) of patients taking
      placebo. Changes in BUN and serum creatinine from baseline were not significantly
      different in the two treatment groups. Baseline BUN and volume of contrast were
      the only independent predictors of CIN. More patients with diabetes had
      development of CIN (5/43; 12%) compared with nondiabetic patients (2/52; 4%), but
      the difference was not significant (P =.15). The incidence of CIN in diabetic
      patients was not different in the two treatment groups. No patient with
      development of CIN required dialysis. Side effects (mostly gastrointestinal)
      occurred in 16% of patients taking NAC and in none of the patients taking
      placebo. Length of stay and hospital charges were not different between the
      treatment groups. CONCLUSIONS: In patients with reduced renal function undergoing
      elective coronary angiography, NAC does not reduce the risk of CIN.

PMID- 14661015
TI  - Is left atrial appendage occlusion during routine coronary artery bypass graft
      surgery useful for stroke prevention?

PMID- 14661016
TI  - Semi-wet peptide/protein array using supramolecular hydrogel.
AB  - The protein microarray is a crucial biomaterial for the rapid and high-throughput
      assay of many biological events where proteins are involved. In contrast to the
      DNA microarray, it has not been sufficiently established because of protein
      instability under the conventional dry conditions. Here we report a novel semi
      wet peptide/protein microarray using a supramolecular hydrogel composed of
      glycosylated amino acetate. The spontaneous gel-formation and amphiphilic
      properties of this supramolecular hydrogel have been applied to a new type of
      peptide/protein gel array that is compatible with enzyme assays. Aqueous cavities
      created in the gel matrix are a suitable semi-wet reaction medium for enzymes,
      whereas the hydrophobic domains of the fibre are useful as a unique site for
      monitoring the reaction. This array system overcomes several drawbacks of
      conventional protein chips, and thus can have potential applications in
      pharmaceutical research and diagnosis.

PMID- 14661017
TI  - Fracture of nanoporous thin-film glasses.
AB  - Fracture of nanoporous thin-film glasses is a significant challenge for the
      integration of these mechanically fragile materials in emerging microelectronic
      and biological technologies. In particular, the integration of these materials
      has been limited by accelerated cracking rates in moist environments leading to
      premature failure. Here, we demonstrate how cracking is affected by aqueous
      solution chemistry, and reveal anomalously high crack-growth rates in hydrogen
      peroxide solutions frequently encountered during device processing or when in
      use. Kinetic mechanisms involving the transport and steric hindrance of reactive
      hydrogen peroxide molecules at the crack tip are proposed. Thin-film design
      strategies that involve energy dissipation by local plasticity in thin ductile
      layers on increasing the resistance to cracking of nanoporous glass layers is
      demonstrated. Understanding how aqueous solutions influence cracking and
      associated device reliability is a fundamental challenge for these promising
      materials to be viable candidates for new technologies.

PMID- 14661018
TI  - Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human
      autoantigen proteinase-3.
AB  - It remains unclear how and why autoimmunity occurs. Here we show evidence for a
      previously unrecognized and possibly general mechanism of autoimmunity. This new
      finding was discovered serendipitously using material from patients with
      inflammatory vascular disease caused by antineutrophil cytoplasmic autoantibodies
      (ANCA) with specificity for proteinase-3 (PR-3). Such patients harbor not only
      antibodies to the autoantigen (PR-3), but also antibodies to a peptide translated
      from the antisense DNA strand of PR-3 (complementary PR-3, cPR-3) or to a mimic
      of this peptide. Immunization of mice with the middle region of cPR-3 resulted in
      production of antibodies not only to cPR-3, but also to the immunogen's sense
      peptide counterpart, PR-3. Both human and mouse antibodies to PR-3 and cPR-3
      bound to each other, indicating idiotypic relationships. These findings indicate
      that autoimmunity can be initiated through an immune response against a peptide
      that is antisense or complementary to the autoantigen, which then induces anti
      idiotypic antibodies (autoantibodies) that cross-react with the autoantigen.

PMID- 14661019
TI  - Differential regulation of interleukin 1 receptor and Toll-like receptor
      signaling by MEKK3.
AB  - Interleukin 1 receptor (IL-1R) and Toll-like receptors (TLRs) induce inflammatory
      genes through the complex of MyD88, IL-1R-associated protein kinase (IRAK) and
      tumor necrosis factor receptor-associated factor 6 (TRAF6), which is believed to
      function 'upstream' of the cascades of IkappaB kinase (IKK) and nuclear factor
      kappaB (NF-kappaB); extracellular signal-regulated protein kinase (ERK); c-Jun N
      terminal kinase (JNK); and p38 mitogen-activated protein kinase (MAPK). Here we
      show that MAPK-ERK kinase kinase (MEKK3) is an essential signal transducer of the
      MyD88-IRAK-TRAF6 complex in IL-1R-TLR4 signaling. MEKK3 forms a complex with
      TRAF6 in response to IL-1 and lipopolysaccharide (LPS) but not CpG, and is
      required for IL-1R- and TLR4-induced IL-6 production. Furthermore, MEKK3 is
      crucial for IL-1- and LPS-induced activation of NF-kappaB and JNK-p38 but not
      ERK, indicating that MAPKs are differentially activated during IL-1R-TLR4
      signaling. These data demonstrate that MEKK3 is crucial for IL-1R and TLR4
      signaling through the IKK-NF-kappaB and JNK-p38 MAPK pathways.*Note: In the
      version of this article originally published online, the third author's name was
      incorrect. The correct author name should be Yong Lin. This error has been
      corrected for the HTML and print versions of this article.

PMID- 14661020
TI  - Two isoforms of otubain 1 regulate T cell anergy via GRAIL.
AB  - The active ubiquitin E3 ligase GRAIL is crucial in the induction of CD4 T cell
      anergy. Here we show that GRAIL is associated with and regulated by two isoforms
      of the ubiquitin-specific protease otubain 1. In lethally irradiated mice
      reconstituted with bone marrow cells from T cell receptor-transgenic mice
      retrovirally transduced to express the genes encoding these proteases, otubain 1
      expressing cells contained negligible amounts of endogenous GRAIL, proliferated
      well and produced large amounts of interleukin 2 after antigenic stimulation. In
      contrast, cells expressing the alternatively spliced isoform, otubain 1
      alternative reading frame 1, contained large amounts of endogenous GRAIL and were
      functionally anergic, and they proliferated poorly and produced undetectable
      interleukin 2 when stimulated in a similar way. Thus, these two proteins have
      opposing epistatic functions in controlling the stability of GRAIL expression and
      the resultant anergy phenotype in T cells.

PMID- 14661021
TI  - Reductive evolution suggested from the complete genome sequence of a plant
      pathogenic phytoplasma.
AB  - The minimal gene set essential for life has long been sought. We report the 860
      kb genome of the obligate intracellular plant pathogen phytoplasma (Candidatus
      Phytoplasma asteris, OY strain). The phytoplasma genome encodes even fewer
      metabolic functions than do mycoplasma genomes. It lacks the pentose phosphate
      cycle and, more unexpectedly, ATP-synthase subunits, which are thought to be
      essential for life. This may be the result of reductive evolution as a
      consequence of life as an intracellular parasite in a nutrient-rich environment.

PMID- 14661022
TI  - Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor
      cells in the hippocampus.
AB  - Oligodendrocyte precursor cells (OPCs) express receptors for many
      neurotransmitters, but the mechanisms responsible for their activation are poorly
      understood. We have found that quantal release of GABA from interneurons elicits
      GABA(A) receptor currents with rapid rise times in hippocampal OPCs. These
      currents did not exhibit properties of spillover transmission or release by
      transporters, and immunofluorescence and electron microscopy suggest that
      interneuronal terminals are in direct contact with OPCs, indicating that these
      GABA currents are generated at direct interneuron-OPC synapses. The reversal
      potential of OPC GABA(A) currents was -43 mV, and interneuronal firing was
      correlated with transient depolarizations induced by GABA(A) receptors; however,
      GABA application induced a transient inhibition of currents mediated by AMPA
      receptors in OPCs. These results indicate that OPCs are a direct target of
      interneuronal collaterals and that the GABA-induced Cl(-) flux generated by these
      events may influence oligodendrocyte development by regulating the efficacy of
      glutamatergic signaling in OPCs.

PMID- 14661023
TI  - Saccades actively maintain perceptual continuity.
AB  - People make saccades--rapid eye movements to a new fixation--approximately three
      times per second. This would seemingly disrupt perceptual continuity, yet our
      brains construct a coherent, stable view of the world from these successive
      fixations. There is conflicting evidence regarding the effects of saccades on
      perceptual continuity: some studies report that they are disruptive, with little
      information carryover between saccades; others report that carryover is
      substantial. Here we show that saccades actively contribute to perceptual
      continuity in humans in two different ways. When bistable stimuli are presented
      intermittently, saccades executed during the blank interval shorten the duration
      of states of ambiguous figures, indicating that saccades can erase immediately
      past perceptual states. On the other hand, they prolong the McCollough effect,
      indicating that saccades strengthen learned contingencies. Our results indicate
      that saccades help, rather than hinder, perceptual continuity.

PMID- 14661024
TI  - Histone H3 lysine 4 methylation patterns in higher eukaryotic genes.
AB  - Lysine residues within histones can be mono-, di - or tri-methylated. In
      Saccharomyces cerevisiae tri-methylation of Lys 4 of histone H3 (K4/H3)
      correlates with transcriptional activity, but little is known about this
      methylation state in higher eukaryotes. Here, we examine the K4/H3 methylation
      pattern at the promoter and transcribed region of metazoan genes. We analysed
      chicken genes that are developmentally regulated, constitutively active or
      inactive. We found that the pattern of K4/H3 methylation shows similarities to S.
      cerevisiae. Tri-methyl K4/H3 peaks in the 5' transcribed region and active genes
      can be discriminated by high levels of tri-methyl K4/H3 compared with inactive
      genes. However, our results also identify clear differences compared to yeast, as
      significant levels of K4/H3 methylation are present on inactive genes within the
      beta-globin locus, implicating this modification in maintaining a 'poised'
      chromatin state. In addition, K4/H3 di-methylation is not genome-wide and di
      methylation is not uniformly distributed throughout the transcribed region. These
      results indicate that in metazoa, di- and tri-methylation of K4/H3 is linked to
      active transcription and that significant differences exist in the genome-wide
      methylation pattern as compared with S. cerevisiae.

PMID- 14661025
TI  - Integration of chemical-genetic and genetic interaction data links bioactive
      compounds to cellular target pathways.
AB  - Bioactive compounds can be valuable research tools and drug leads, but it is
      often difficult to identify their mechanism of action or cellular target. Here we
      investigate the potential for integration of chemical-genetic and genetic
      interaction data to reveal information about the pathways and targets of
      inhibitory compounds. Taking advantage of the existing complete set of yeast
      haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic)
      profiles for 12 compounds. In addition to a set of compound-specific
      interactions, the chemical-genetic profiles identified a large group of genes
      required for multidrug resistance. In particular, yeast mutants lacking a
      functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may
      be conserved in mammalian cells. By filtering chemical-genetic profiles for the
      multidrug-resistant genes and then clustering the compound-specific profiles with
      a compendium of large-scale genetic interaction profiles, we were able to
      identify target pathways or proteins. This method thus provides a powerful means
      for inferring mechanism of action.

PMID- 14661026
TI  - Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping.
AB  - The use of near-infrared or infrared photons is a promising approach for
      biomedical imaging in living tissue. This technology often requires exogenous
      contrast agents with combinations of hydrodynamic diameter, absorption, quantum
      yield and stability that are not possible with conventional organic fluorophores.
      Here we show that the fluorescence emission of type II quantum dots can be tuned
      into the near infrared while preserving absorption cross-section, and that a
      polydentate phosphine coating renders them soluble, disperse and stable in serum.
      We then demonstrate that these quantum dots allow a major cancer surgery,
      sentinel lymph node mapping, to be performed in large animals under complete
      image guidance. Injection of only 400 pmol of near-infrared quantum dots permits
      sentinel lymph nodes 1 cm deep to be imaged easily in real time using excitation
      fluence rates of only 5 mW/cm(2). Taken together, the chemical, optical and in
      vivo data presented in this study demonstrate the potential of near-infrared
      quantum dots for biomedical imaging.

PMID- 14661027
TI  - Unraveling protein interaction networks with near-optimal efficiency.
AB  - The functional characterization of genes and their gene products is the main
      challenge of the genomic era. Examining interaction information for every gene
      product is a direct way to assemble the jigsaw puzzle of proteins into a
      functional map. Here we demonstrate a method in which the information gained from
      pull-down experiments, in which single proteins act as baits to detect
      interactions with other proteins, is maximized by using a network-based strategy
      to select the baits. Because of the scale-free distribution of protein
      interaction networks, we were able to obtain fast coverage by focusing on highly
      connected nodes (hubs) first. Unfortunately, locating hubs requires prior global
      information about the network one is trying to unravel. Here, we present an
      optimized 'pay-as-you-go' strategy that identifies highly connected nodes using
      only local information that is collected as successive pull-down experiments are
      performed. Using this strategy, we estimate that 90% of the human interactome can
      be covered by 10,000 pull-down experiments, with 50% of the interactions
      confirmed by reciprocal pull-down experiments.

PMID- 14661028
TI  - Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells.
AB  - We have observed karyotypic changes involving the gain of chromosome 17q in three
      independent human embryonic stem (hES) cell lines on five independent occasions.
      A gain of chromosome 12 was seen occasionally. This implies that increased dosage
      of chromosome 17q and 12 gene(s) provides a selective advantage for the
      propagation of undifferentiated hES cells. These observations are instructive for
      the future application of hES cells in transplantation therapies in which the use
      of aneuploid cells could be detrimental.

PMID- 14661029
TI  - Recognition of small interfering RNA by a viral suppressor of RNA silencing.
AB  - RNA silencing (also known as RNA interference) is a conserved biological response
      to double-stranded RNA that regulates gene expression, and has evolved in plants
      as a defence against viruses. The response is mediated by small interfering RNAs
      (siRNAs), which guide the sequence-specific degradation of cognate messenger
      RNAs. As a counter-defence, many viruses encode proteins that specifically
      inhibit the silencing machinery. The p19 protein from the tombusvirus is such a
      viral suppressor of RNA silencing and has been shown to bind specifically to
      siRNA. Here, we report the 1.85-A crystal structure of p19 bound to a 21
      nucleotide siRNA, where the 19-base-pair RNA duplex is cradled within the concave
      face of a continuous eight-stranded beta-sheet, formed across the p19 homodimer
      interface. Direct and water-mediated intermolecular contacts are restricted to
      the backbone phosphates and sugar 2'-OH groups, consistent with sequence
      independent p19-siRNA recognition. Two alpha-helical 'reading heads' project from
      opposite ends of the p19 homodimer and position pairs of tryptophans for stacking
      over the terminal base pairs, thereby measuring and bracketing both ends of the
      siRNA duplex. Our structure provides an illustration of siRNA sequestering by a
      viral protein.

PMID- 14661030
TI  - X-ray structure of a protein-conducting channel.
AB  - A conserved heterotrimeric membrane protein complex, the Sec61 or SecY complex,
      forms a protein-conducting channel, allowing polypeptides to be transferred
      across or integrated into membranes. We report the crystal structure of the
      complex from Methanococcus jannaschii at a resolution of 3.2 A. The structure
      suggests that one copy of the heterotrimer serves as a functional translocation
      channel. The alpha-subunit has two linked halves, transmembrane segments 1-5 and
      6-10, clamped together by the gamma-subunit. A cytoplasmic funnel leading into
      the channel is plugged by a short helix. Plug displacement can open the channel
      into an 'hourglass' with a ring of hydrophobic residues at its constriction. This
      ring may form a seal around the translocating polypeptide, hindering the
      permeation of other molecules. The structure also suggests mechanisms for signal
      sequence recognition and for the lateral exit of transmembrane segments of
      nascent membrane proteins into lipid, and indicates binding sites for partners
      that provide the driving force for translocation.

PMID- 14661031
TI  - Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos.
AB  - In mammals, dosage compensation ensures equal X-chromosome expression between
      males (XY) and females (XX) by transcriptionally silencing one X chromosome in XX
      embryos. In the prevailing view, the XX zygote inherits two active X chromosomes,
      one each from the mother and father, and X inactivation does not occur until
      after implantation. Here, we report evidence to the contrary in mice. We find
      that one X chromosome is already silent at zygotic gene activation (2-cell
      stage). This X chromosome is paternal in origin and exhibits a gradient of
      silencing. Genes close to the X-inactivation centre show the greatest degree of
      inactivation, whereas more distal genes show variable inactivation and can
      partially escape silencing. After implantation, imprinted silencing in
      extraembryonic tissues becomes globalized and more complete on a gene-by-gene
      basis. These results argue that the XX embryo is in fact dosage compensated at
      conception along much of the X chromosome. We propose that imprinted X
      inactivation results from inheritance of a pre-inactivated X chromosome from the
      paternal germ line.

PMID- 14661032
TI  - Fibrillin-1 expression in normal and fibrotic rat liver and in cultured hepatic
      fibroblastic cells: modulation by mechanical stress and role in cell adhesion.
AB  - Fibrillin-1, together with elastin, is the main component of elastic fibers found
      throughout the extracellular space and responsible for the biomechanical
      properties of most tissues and organs. In this work, fibrillin-1 expression and
      modulation were explored in experimental rat liver fibrosis and in vitro;
      furthermore, the role of fibrillin-1 fragments on cell adhesion was analyzed.
      Fibrosis was induced by subjecting rats to common bile duct ligation for 72 h and
      7 days or carbon tetrachloride (CCl(4)) treatment for 2 and 6 weeks.
      Immunohistochemistry showed that, after bile duct ligation, fibrillin-1, elastin,
      and alpha-smooth muscle actin colocalized in the developing portal connective
      tissue. In CCl(4)-treated animals, a similar colocalization was observed in
      septa; however, elastin deposition was not observed around activated alpha-smooth
      muscle actin-positive stellate cells of the parenchyma. Treatment with the
      profibrogenic mediator transforming growth factor-beta1 (TGF-beta1) greatly
      increased the fibrillin-1 expression of cultured liver fibroblasts. The level of
      fibrillin-1 expression was significantly higher in cells grown in restrained
      (stressed) collagen lattices compared with those grown in unrestrained collagen
      lattices. Cell adhesion on the C-terminal fragment of fibrillin-1 containing the
      RGD sequence (rF6H) slightly increased (between 0.3 and 2.5 microg/ml) and
      decreased at higher concentrations, while adhesion on the N-terminal fragment of
      fibrillin-1 (rF16) was dose-dependently decreased. In addition, the rF16 fragment
      decreased cell adhesion to fibronectin. In conclusion, our study illustrates the
      important deposition of fibrillin-1 that occurs in two mechanistically distinct
      settings of liver fibrogenesis. Furthermore, the induction of fibrillin-1
      expression by TGF-beta1 and mechanical stress, and the antiadhesive properties of
      fibrillin-1 fragments suggest important implications for physiological and
      pathological fibrillin-1 catabolism during tissue remodeling.

PMID- 14661033
TI  - Hypoxia increases Hsp90 binding to eNOS via PI3K-Akt in porcine coronary artery
      endothelium.
AB  - This study examines the molecular mechanisms by which hypoxia regulates
      phosphorylated endothelial nitric oxide synthase (eNOS) activity and NO
      production in porcine coronary artery endothelial cells (PCAEC). Exposure to
      hypoxia (pO(2)=10 mmHg) for periods up to 3 h resulted in a time-dependent
      increase in eNOS protein expression and an early (15 min) and sustained increase
      in eNOS phosphorylation at Ser-1177. Exposure to hypoxia for 30 min led to a
      doubling in eNOS activity (control=6.2+/-4.4 vs hypoxia=14.1+/-5.0 fmol
      cGMP/microg protein, P<0.05) and NO release (control=5.9+/-0.8 vs hypoxia=11.8+/
      1.2 nM/microg protein, P<0.05). Hypoxia also led to a significant increase in Akt
      phosphorylation and upregulation of Hsp90 binding to eNOS. Pretreatment of cells
      with either 1 microg/ml geldanamycin (a specific inhibitor of Hsp90) or 500 nM
      wortmannin (a specific PI3 kinase inhibitor) suppressed hypoxia-stimulated Akt
      and eNOS phosphorylation and significantly attenuated hypoxia-stimulated Hsp90
      binding to eNOS. Both eNOS activity and NO production were inhibited by
      geldanamycin and wortmannin. Although hypoxia led to early activation of p42/44
      mitogen-activated protein kinases (MAPK), inhibition of their pathway by PD98059
      did not suppress hypoxia-stimulated eNOS phosphorylation and eNOS activity. These
      data demonstrate that hypoxia leads to increased eNOS phosphorylation via
      stimulated Hsp90 binding to eNOS and activation of the PI3-Akt pathway. We
      conclude that a coordinated interaction between Hsp90 and PI3-Akt may be an
      important mechanism by which eNOS activity and NO production is upregulated in
      hypoxic heart.

PMID- 14661034
TI  - Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in
      the alpha beta spectrin self-association binding site.
AB  - We studied an infant with severe neonatal hemolytic anemia and hyperbilirubinemia
      that evolved into a partially compensated ellipto-poikilocytic anemia. His father
      had typical elliptocytosis. Their erythrocyte membranes demonstrated structural
      and functional defects in spectrin. Genetic studies revealed that the proband and
      his father were heterozygous for an alpha-spectrin mutation, Ile24Thr, in the
      alpha beta spectrin self-association binding site. The proband also carried the
      low expression allele alpha(LELY) in trans, influencing the clinical phenotype.
      The importance of isoleucine in this position of the proposed triple helical
      model of spectrin repeats is highlighted by its evolutionary conservation in all
      alpha spectrins from Drosophila to humans. Molecular modeling demonstrated that
      replacement of a hydrophobic isoleucine with a hydrophilic threonine disrupts
      highly conserved hydrophobic interactions in the interior of the spectrin triple
      helix critical for spectrin function.

PMID- 14661035
TI  - A distinct phenotype characterizes tumors from a putative genetic trait involving
      chondrosarcoma and breast cancer occurring in the same patient.
AB  - Recently, we documented an increased risk for the occurrence of breast- and
      cartilaginous tumors in the same patient, statistically pointing towards a
      potential genetic trait. This trait is most probably not associated with
      mutations in the two major hereditary breast cancer genes since no cases of
      enchondroma or chondrosarcoma were found in Dutch BRCA1 and BRCA2 families. We
      were able to collect and review the tumor tissue samples from 34 patients with
      both breast- and cartilaginous tumors and compared histopathological and
      immunohistochemical features of these tumors with controls. Breast cancer
      controls were available from literature data generated to compare familial breast
      cancers with nonselected cases. Clinical markers for chondrosarcoma controls were
      collected from the Netherlands Committee of Bone Tumors. Immunohistochemical data
      on chondro-tumor controls were available from our own files. Breast tumors of
      patients with cartilaginous sarcomas showed a significantly higher mitotic count
      (P=0.001), contained less lymphocyte infiltrate (P=0.025) and less nuclear
      pleomorphism. Remarkably, all cartilaginous tumors are of one common histological
      category originating centrally (P=0.014). Estrogen receptor and p53 expression
      were significantly higher (P<0.001) in breast cancer associated with chondro
      tumors. p21 staining was more often negative in chondro-tumors associated with
      breast cancer. In seven cases of breast cancer, we found a slight decrease in
      CHEK2 expression. However, we could not identify the CHEK2 1100delC mutation in
      these cases nor in cases with normal CHEK2 expression. Hierarchical cluster
      analysis of all parameters within chondro-tumor-associated breast cancer
      specimens revealed two different subgroups, the largest one associated with
      estrogen receptor-positive breast cancer, which may distinguish sporadic cases
      from those belonging to the potential genetic trait. These distinct phenotypic
      findings support the existence of a new hitherto unrecognized syndrome,
      characterized by an increased risk to develop both breast cancer and centrally
      originating cartilaginous tumors.

PMID- 14661036
TI  - Defibrotide in the treatment of children with veno-occlusive disease (VOD): a
      retrospective multicentre study demonstrates therapeutic efficacy upon early
      intervention.
AB  - Veno-occlusive disease (VOD) of the liver is a complication observed particularly
      in patients undergoing hematopoietic stem cell transplantation (HSCT).
      Defibrotide (DF) is a polydeoxyribonucleotide with aptameric activity on
      endothelium. We evaluated in a retrospective analysis the efficacy of DF in
      pediatric patients developing hepatic VOD after HSCT.A total of 45 patients
      between 0.2 and 20 years (median age: 8.2 years) with hepatic VOD were treated
      with DF: 22 patients (49%) met risk criteria for severe or progressive disease
      and 23 (51%) for moderately severe and mild disease. The median duration of DF
      treatment was 17 days. In all, 34 patients (76%) achieved complete response (CR)
      with a survival rate of 64% at day 100. CR rate in patients with severe disease
      was 50% with long-term survival of 36%. The average DF dose in the CR group was
      45 mg/kg/day and in the no responder (NR) group 27 mg/kg/day. The use of
      additional drugs besides DF to treat VOD made no difference in the outcome
      compared to DF alone. The average interval from diagnosis to start of DF was 1
      day in the CR and 5.5 days in NR group. In multivariate analysis, early
      intervention remained the only significant factor for a CR.

PMID- 14661037
TI  - Toward a myeloablative regimen with clinical potential: II. Treosulfan induces
      specific skin graft tolerance across haploidentical MHC barriers.
AB  - Treosulfan is a water-soluble structural analog of busulfan, acting as a prodrug
      of alkylating epoxide species. It does not induce severe hepatotoxicity or veno
      occlusive disease at or above the maximum tolerated dose, lacks significant
      nonhematological toxicity and has a limited organ toxicity. It is mainly
      indicated for the treatment of patients with ovarian cancer. In the present
      study, we report that permanent donor-specific tolerance and stable mixed
      multilineage chimerism can successfully be achieved across haploidentical MHC
      barriers when Treosulfan is administered in combination with anti-T-cell mAb and
      T-cell-depleted donor bone marrow cells. Furthermore, we show that less T-cell
      suppression is required when Treosulfan is included in the conditioning regimen.
      In conclusion, Treosulfan is a well-tolerated myeloablative agent with a low
      toxicity, and is a promising candidate drug for conditioning prior to bone marrow
      transplantation.

PMID- 14661039
TI  - Chemotherapy for ovarian cancer: yesterday, today and tomorrow.

PMID- 14661040
TI  - Primary ovarian cancer chemotherapy: current standards of care.
AB  - Chemotherapy has been regarded as standard therapy for the majority of women with
      advanced epithelial ovarian cancer for several decades, with this role filled
      largely by the alkylating agents - used as monotherapy - until the mid-1980s. The
      activity of cisplatin in this disorder was established during the 1970s, and
      combinations of cisplatin and an alkylating agent were widely used during the
      late 1980s. However, further research prompted by continuing concerns over poor
      survival and tolerability led to the adoption of paclitaxel in combination with
      either cisplatin or carboplatin as first-line therapy in ovarian cancer during
      the 1990s. Most recent research has focused on further optimisation of these
      regimens to maximise clinical benefit while minimising toxicity, and
      investigations into alternative taxanes (e.g. docetaxel), other novel agents and
      new treatment schedules are ongoing.

PMID- 14661041
TI  - Docetaxel: an alternative taxane in ovarian cancer.
AB  - The taxanes paclitaxel and docetaxel are potent chemotherapeutic agents that
      block tubulin depolymerisation, leading to the inhibition of microtubule dynamics
      and cell cycle arrest. Although docetaxel and paclitaxel share a mutual tubulin
      binding site, mechanistic and pharmacological differences exist between these
      agents. For example, docetaxel has increased potency and an improved therapeutic
      index compared with paclitaxel, and its short 1-h infusion offers a substantial
      clinical advantage over the prolonged infusion durations required with
      paclitaxel. In clinical studies, docetaxel monotherapy demonstrated good response
      rates and an acceptable toxicity profile in both paclitaxel- and platinum
      refractory ovarian cancer patients. In particular, neurotoxicity - a dominant
      side effect with both paclitaxel and cisplatin - occurs at a low incidence with
      docetaxel, making docetaxel a promising agent for combining cisplatin and other
      platinum compounds. In Phase II studies, the combination of docetaxel with either
      cisplatin or carboplatin has yielded impressive response rates of 69-74 and 81
      87%, respectively. Furthermore, Phase III data suggest that docetaxel-carboplatin
      and paclitaxel-carboplatin are similarly efficacious with respect to progression
      free survival and clinical response, although neurotoxicity occurs more
      frequently with the paclitaxel regimen. While paclitaxel-carboplatin remains the
      standard treatment for the management of advanced ovarian cancer, docetaxel
      carboplatin appears to be a promising alternative, particularly in terms of
      minimising the incidence and severity of peripheral neuropathy.

PMID- 14661042
TI  - The taxanes: toxicity and quality of life considerations in advanced ovarian
      cancer.
AB  - The taxanes paclitaxel and docetaxel show good activity in the management of
      advanced ovarian cancer when used in conjunction with platinum agents.
      Accumulating evidence from clinical studies, particularly the latest results from
      the phase III comparative SCOTROC study, indicates that the two drugs confer
      similar rates of tumour response and survival in women with this condition.
      However, it is clear that paclitaxel and docetaxel differ in their tolerability
      profiles and in other respects, and cannot be regarded as directly equivalent
      drugs. In particular, paclitaxel is associated with significant neurotoxicity;
      peripheral neuropathy has also been reported with docetaxel, but to a lesser
      extent. Neutropenia appears more prevalent with docetaxel than with paclitaxel,
      although clinical trial data show that this adverse effect is manageable and need
      not compromise dose delivery. Docetaxel is also associated with potential
      benefits accruing from shorter infusion times and lack of need for premedication
      with intravenous histamine H(1) and H(2) antagonists. Emerging quality of life
      data are expected to shed further light on the overall benefit of chemotherapy in
      women with advanced ovarian cancer in general, and on taxane-platinum
      combinations in particular.

PMID- 14661043
TI  - Resistance to chemotherapy in advanced ovarian cancer: mechanisms and current
      strategies.
AB  - Although treatment for advanced epithelial ovarian cancer has improved over
      recent years with the introduction of taxane-platinum chemotherapy, the majority
      of patients will relapse, and in most the disease remains incurable. A thorough
      understanding of drug resistance mechanisms is needed, as this remains the
      largest obstacle in treating patients with recurrent disease. Multidrug
      resistance proteins, mismatch repair processes and alterations in the p53 pathway
      are examples of properties within tumour cells that may lead to drug resistance.
      Novel agents designed to circumvent these mechanisms (e.g. PSC 833, ONYX-015 and
      ADP53) are currently being investigated for ovarian cancer patients. Further
      improvements may result from the optimisation of existing first-line regimens
      with more creative schedules, perhaps involving sequential or intraperitoneal
      administration of existing drugs, and the incorporation of newer noncross
      resistant drugs.

PMID- 14661044
TI  - Docetaxel: promising and novel combinations in ovarian cancer.
AB  - Despite considerable progress over the past two decades in the management of
      advanced ovarian cancer, the majority of patients with this type of malignancy
      still die from their disease, and the search for new and improved first-line and
      salvage chemotherapy regimens continues. As part of this work, the antitumour
      activity and effect on survival of new chemotherapy combinations containing the
      novel taxane docetaxel are being explored. Dual therapy with docetaxel plus a
      camptothecin (a topoisomerase inhibitor) has shown promise in second-line
      treatment, and preliminary data indicate good activity of docetaxel in
      combination with gemcitabine. Triple-therapy studies have produced mixed results,
      but encouraging activity has been reported when the anthracycline, epirubicin, is
      added to docetaxel and carboplatin - sequential therapy with docetaxel, cisplatin
      and epirubicin is currently being assessed. Combinations of docetaxel,
      carboplatin and gemcitabine may also be of future interest. Early efficacy and
      tolerability results with novel combination chemotherapy regimens involving
      docetaxel thus offer the promise of additional progress in the chemotherapy of
      advanced ovarian cancer, and further trials should be encouraged.

PMID- 14661045
TI  - The 'Iressa' Clinical Experience Meeting. June 2003, Madrid, Spain. Proceedings
      and abstracts.

PMID- 14661046
TI  - Extensive experience of disease control with gefitinib and the role of prognostic
      markers.
AB  - Traditionally, the efficacy of an anticancer agent has been measured by response
      rate. With the development of biological molecular-targeted agents, which have a
      different mechanism of action from conventional agents, it may be appropriate to
      consider alternative criteria that reflect the positive effect of these
      biological agents on disease control, palliation, symptom improvement and quality
      of life. One such targeted agent is the orally active epidermal growth factor
      receptor tyrosine kinase inhibitor gefitinib ("Iressa", ZD1839). This article
      reviews the clinical experience of patients with advanced/metastatic non-small
      cell lung cancer, who have received gefitinib as part of a clinical trial or
      through the "Iressa" Expanded Access Programme. Disease-control rates of
      approximately 50% were observed in some Expanded Access Programme series,
      comparable with results obtained from Phase II trials. Symptom improvement was
      also reported. Information that will help identify those patients most likely to
      respond to treatment will become increasingly important. Therefore, the possible
      role of prognostic markers and the relationship between epidermal growth factor
      receptor status and response to gefitinib has been investigated. No clear
      association between epidermal growth factor receptor expression and response was
      observed. Future studies of other biomarkers in the epidermal growth factor
      receptor pathway should help to identify which patients are likely to benefit
      most from gefitinib.

PMID- 14661047
TI  - Tolerability of gefitinib in patients receiving treatment in everyday clinical
      practice.
AB  - Gefitinib ("Iressa", ZD1839), an epidermal growth factor receptor tyrosine kinase
      inhibitor, has recently been approved in several countries for use in advanced or
      metastatic non-small-cell lung cancer (NSCLC). In contrast to chemotherapies,
      which are generally used at or near their maximum-tolerated dose (MTD), gefitinib
      is used at an optimal biological dose (250 mg day(-1)), which is substantially
      below its MTD, minimising the risk of adverse events without compromising
      efficacy. Tolerability data from the compassionate use of gefitinib in the
      "Iressa" Expanded Access Programme support the favourable safety profile of the
      agent reported in Phase I and II trials. In both settings, the majority of
      adverse drug reactions were mild/moderate and consisted mainly of grade 1/2
      diarrhoea and skin rash. Although skin rash has been suggested to predict
      response to gefitinib, available data do not support this hypothesis. Overall,
      these tolerability data demonstrate that gefitinib has a relatively benign side
      effect profile and is a well-tolerated treatment option for patients with
      previously treated NCSLC, who currently have few alternatives.

PMID- 14661048
TI  - Quality-of-life benefits and evidence of antitumour activity for patients with
      brain metastases treated with gefitinib.
AB  - Brain metastases are a common complication of non-small-cell lung cancer (NSCLC).
      The role of chemotherapy in the treatment of brain metastases has not been
      clearly defined. Emerging case reports of patients with recurrent NSCLC treated
      as part of the Expanded Access Programme reveal that gefitinib ("Iressa", ZD1839)
      has clinical activity in some patients with brain metastases. Here, we describe a
      number of case studies documenting the response of patients with brain metastases
      to treatment with gefitinib. Many of these patients had quality-of-life benefits
      with improvement of neurological and systemic symptoms; some had a partial
      response of their brain metastases and even complete responses have been seen in
      a few patients. One case report also describes a durable long-term response with
      concurrent treatment with gefitinib and radiotherapy. Such results call for
      larger trials designed to evaluate and define the role of gefitinib in the
      treatment of brain metastases in NSCLC patients, either as a single agent or in
      combination with radiation therapy.

PMID- 14661049
TI  - Lessons from the ("Iressa" Expanded Access Programme: gefitinib in special non
      small-cell lung cancer patient populations.
AB  - Some subgroups of patients with advanced/metastatic non-small-cell lung cancer
      (NSCLC) are frequently considered ineligible for the aggressive, platinum-based
      combination chemotherapy that is the recommended treatment. Elderly patients may
      have a poorer tolerance of chemotherapy due to impaired organ function and
      frequent comorbidities; patients with poor performance status (PS; > or =2 due to
      NSCLC and/or coexisting illnesses) are often considered unfit for chemotherapy;
      other patients may be unable or unwilling to endure the toxicity or inconvenience
      of chemotherapy. These patient groups may benefit from novel, relatively nontoxic
      treatment modalities. Gefitinib ("Iressa", ZD1839) 250 mg day(-1) is well
      tolerated and has proven antitumour and symptom improvement activity in patients
      with previously treated NSCLC. Phase II trials (IDEAL 1 and 2) of gefitinib in
      advanced/metastatic NSCLC included 70 out of 425 (16.5%) patients with PS > or
      =2, and their response rate, clinical benefit rate and rates of adverse events
      were similar to those of the overall trial population. In addition, many patients
      with advanced/metastatic NSCLC with poor PS or advanced age have received
      gefitinib 250 mg day(-1) in an Expanded Access Programme (EAP). Observations from
      the EAP support those of IDEAL 1 and 2, and indicate that gefitinib 250 mg day(
      1) warrants further investigation in these patient groups.

PMID- 14661052
TI  - Glypican-3 is involved in cellular protection against mitoxantrone in gastric
      carcinoma cells.
AB  - Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was
      found on mRNA and protein levels in the atypical multidrug-resistant gastric
      carcinoma cell line EPG85-257RNOV, which was established by in vitro selection
      against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug
      resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was
      transfected with an expression vector construct carrying an anti-GPC3 hammerhead
      ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell
      clones, the GPC3-specific mRNA and corresponding protein expression levels were
      decreased to levels that are similar to those observed in nonresistant, parental
      cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone
      resistance level up to 21% of the original resistance and the crossresistance
      against etoposide to 33% of the original value. This reversal of drug resistance
      was accompanied by an increased cellular mitoxantrone accumulation in the anti
      GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is
      involved in the cellular protection against mitoxantrone in the atypical
      multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.

PMID- 14661053
TI  - Five carboxyl-terminal residues of neuregulin2 are critical for stimulation of
      signaling by the ErbB4 receptor tyrosine kinase.
AB  - The neuregulins (NRGs) are members of the epidermal growth factor (EGF) family of
      peptide growth factors. These hormones are agonists for the ErbB family of
      receptor tyrosine kinases, a family that includes the epidermal growth factor
      receptor (EGFR/ErbB1), ErbB2/Neu/HER2, ErbB3/HER3, and ErbB4/HER4. We recently
      observed that the EGF family hormone NRG2beta is a potent agonist for ErbB4. In
      contrast, NRG2alpha, a splicing isoform of the same gene that encodes NRG2beta,
      is a poor ErbB4 agonist. We hypothesized that carboxyl-terminal residues of
      NRG2beta are critical for stimulation of ErbB4 tyrosine phosphorylation and
      coupling to downstream signaling events. Here, we demonstrate that the
      substitution of a lysine residue for Phe45 in NRG2beta results in reduced ligand
      potency. We also demonstrate that substitution of a phenylalanine for Lys45 in
      NRG2alpha results in increased ligand potency. Finally, analyses of the gain-of
      function NRG2alpha Chg5 mutant demonstrate that Gln43, Met47, Asn49, and Phe50
      regulate ligand efficacy. Thus, these data indicate that carboxyl-terminal
      residues of NRG2beta are critical for activation of ErbB4 signaling. Moreover,
      these NRG2alpha and NRG2beta mutants reveal new insights into models for ligand
      induced ErbB family receptor tyrosine phosphorylation and coupling to downstream
      signaling events.

PMID- 14661054
TI  - Plakoglobin (gamma-catenin) has TCF/LEF family-dependent transcriptional activity
      in beta-catenin-deficient cell line.
AB  - Beta-catenin is an essential element for the transcriptional activation of target
      genes in the Wnt signaling cascade and is also a cell adhesion molecule that
      couples with cadherins. Although plakoglobin (gamma-catenin), a closely related
      homologue of beta-catenin, is also known to be a cell adhesion molecule, its
      function as a transcriptional factor has not been revealed in detail. Using a
      human malignant mesothelioma cell line, NCI-H28, in which we have identified a
      homozygous deletion of the beta-catenin gene, we studied whether plakoglobin has
      a T-cell factor/lymphocyte enhancer factor (TCF/LEF) family-dependent
      transcriptional activity. Transfection with the wild-type plakoglobin expression
      vector induced accumulation of plakoglobin in the nucleus. Immunoprecipitation
      assay with cotransfection of plakoglobin and either TCF-4 or LEF-1 detected
      binding of plakoglobin to TCF-4 or LEF-1. Luciferase reporter assay demonstrated
      transcriptional activity of the wild-type plakoglobin when transfected with
      TCF/LEF, although plakoglobin showed less activity than beta-catenin. Exogenous
      plakoglobin was also shown to promote entrance of exogenous beta-catenin into the
      nuclei. Furthermore, small interfering RNA directed against plakoglobin
      suppressed expression of endogenous plakoglobin and its transcriptional activity,
      suggesting that endogenous plakoglobin has a weak transcriptional activity. These
      results suggest that plakoglobin can activate the Wnt signaling cascade directly
      without interaction of beta-catenin, and that plakoglobin has multiple functions
      as a transcriptional activator and a cell adhesion molecule like beta-catenin.

PMID- 14661055
TI  - Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast
      tumors.
AB  - Altered cell adhesion is causally involved in tumor progression, and the
      identification of novel adhesion molecules altered in tumors is crucial for our
      understanding of tumor biology and for the development of new prognostic and
      therapeutic strategies. Here, we provide evidence for the epigenetic
      downregulation in breast tumors of the A Desintegrin And Metalloprotease domain
      23 gene (ADAM 23), a member of a new family of surface molecules with roles in
      cell-cell adhesion and/or cell-matrix interactions. We examined the mRNA
      expression and methylation status of the 5' upstream region of the ADAM23 gene in
      different breast tumor cell lines as well as in primary breast tumors. We found
      ADAM23 5' hypermethylation in eight out of 12 (66.7%) tumor cell lines and in
      nine out of 13 (69.2%) primary tumors. Promoter hypermethylation was strongly
      associated with reductions in both mRNA and protein expression, with a threshold
      of 40-60% of modified CpG dinucleotides being required for the complete silencing
      of ADAM23 mRNA expression. Treatment of MCF-7 and SKBR-3 cell lines with 5'-Aza
      2'-deoxycytidine led to a reactivation of ADAM23 mRNA expression and a marked
      decrease in the methylation level. It is worth noting that primary breast tumors
      with a more advanced grade showed a higher degree of methylation, suggesting that
      the adhesion molecule ADAM23 may be downregulated during the progression of
      breast cancer. Oncogene (2004) 23, 1481-1488. doi:10.1038/sj.onc.1207263
      Published online 8 December 2003

PMID- 14661056
TI  - RNA interference targeting the M2 subunit of ribonucleotide reductase enhances
      pancreatic adenocarcinoma chemosensitivity to gemcitabine.
AB  - Ribonucleotide reductase is emerging as an important determinant of gemcitabine
      chemoresistance in human cancers. Activity of this enzyme, which catalyses
      conversion of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotides, is
      modulated by levels of its M2 subunit (RRM2). Here we show that RRM2
      overexpression is associated with gemcitabine chemoresistance in pancreatic
      adenocarcinoma cells, and that suppression of RRM2 expression using RNA
      interference mediated by small interfering RNA (siRNA) enhances gemcitabine
      induced cytotoxicity in vitro. We demonstrate the ability of systemically
      administered RRM2 siRNA to suppress tumoral RRM2 expression in an orthotopic
      xenograft model of pancreatic adenocarcinoma. Synergism between RRM2 siRNA and
      gemcitabine results in markedly suppressed tumor growth, increased tumor
      apoptosis and inhibition of metastasis. Our findings confirm the importance of
      RRM2 in pancreatic adenocarcinoma gemcitabine chemoresistance. This is the first
      demonstration that systemic delivery of siRNA-based therapy can enhance the
      efficacy of an anticancer nucleoside analog.

PMID- 14661057
TI  - 'Designer' tumors in mice.
AB  - We have developed and tested successfully a general method based on Cre-mediated
      recombination that can be used for ubiquitous or tissue-specific expression of
      protein products, including tumor-inducing oncoproteins. Depending on the
      specificity of a chosen promoter driving cre expression, tumors develop by design
      in bitransgenic mouse progeny derived by crossing Cre-producing mice with
      partners carrying a dormant oncogenic transgene (targeted into the 3' noncoding
      region of the cytoplasmic beta-actin locus) that becomes functional after
      excision of a 'floxed' DNA segment. To provide proof-of-principle, we have used
      as models transgenes encoding the polyomavirus middle T antigen (PVMT) and the T
      antigens of the SV40 early region (SVER). Cre-dependent activation of widespread
      SVER expression resulted in hyperplasias or invasive tumors affecting particular
      visceral smooth muscles, whereas Cre-dependent, mammary gland-specific expression
      of PVMT-induced adenocarcinomas, according to plan. Unexpectedly, we also
      encountered spontaneous (Cre-independent) oncogene expression occurring as a rare
      event, which simulates the initiation of sporadic tumors and leads to PVMT
      induced hemangiomas and mammary carcinomas or SVER-induced disseminated sarcomas,
      thus, revealing particular tissue susceptibilities to the actions of these
      oncoproteins.

PMID- 14661058
TI  - Plakoglobin is a new target gene of histone deacetylase in human fibrosarcoma
      HT1080 cells.
AB  - Histone deacetylase (HDAC) plays a key role in gene expression, by suppressing
      the transcription of a number of target genes. Identification of such genes is
      important for deciphering the functional role of HDAC. Here, using cancer gene
      focused DNA microarray analysis, we identified plakoglobin as a new target gene
      of HDAC. Functional inhibition of HDAC by its specific inhibitors induced the
      expression of plakoglobin by eight-fold in human fibrosarcoma HT1080 cells.
      However, the expression of beta-catenin, which is closely related to plakoglobin,
      was not altered, implying the specific function of HDAC in plakoglobin
      expression. Using antiacetyl-H4 antibody, chromatin immunoprecipitation analysis
      revealed that the distal region (-945 approximately -646) of the promoter of
      plakoglobin is responsible for the HDAC-mediated repression of the gene.
      Moreover, the induced expression of plakoglobin by the inhibition of HDAC
      activated the Tcf/Lef-dependent luciferase reporter gene, a well-known downstream
      effector of the Wnt signaling pathway. Furthermore, transient transfection of
      plakoglobin also activated Tcf/Lef reporter gene expression. Taken together, our
      results demonstrate that plakoglobin is a new target gene governed by HDAC, and
      that it acts as an oncogene in HT1080 cells.

PMID- 14661059
TI  - DLC-1 operates as a tumor suppressor gene in human non-small cell lung
      carcinomas.
AB  - The deleted in liver cancer (DLC-1) gene at chromosome 8p21-22 is altered mainly
      by genomic deletion or aberrant promoter methylation in a large number of human
      cancers such as breast, liver, colon and prostate and is known to have an
      inhibitory effect on breast and liver tumor cell growth. Given the high frequency
      of deletion involving region 8p21-22 in human non-small cell lung carcinoma
      (NSCLC), we examined alterations of DLC-1 in a series of primary tumors and tumor
      cell lines and tested effects of DLC-1 on tumor cell growth. A significant
      decrease or absence of the DLC-1 mRNA expression was found in 95% of primary
      NSCLC (20/21) and 58% of NSCLC cell lines (11/19). Transcriptional silencing of
      DLC-1 was primarily associated with aberrant DNA methylation, rather than genomic
      deletion as 5-aza-2'-deoxycytidine induced reactivation of DLC-1 expression in
      82% (9/11) NSCLC cell lines showing downregulated DLC-1. It was further evidenced
      by an aberrant DLC-1 promoter methylation pattern, which was detected by Southern
      blotting in 73% (8/11) of NSCLC cell lines with downregulation of the gene. The
      transfer of DLC-1 into three DLC-1 negative cell lines caused a significant
      inhibition in cell proliferation and/or a decrease in colony formation.
      Furthermore, stable transfer of DLC-1 abolished tumorigenicity in nude mice of
      two cell lines, suggesting that DLC-1 plays a role in NSCLC by acting as a bona
      fide new tumor suppressor gene.

PMID- 14661060
TI  - Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein
      degradation.
AB  - The Cbl family proteins Cbl, Cbl-b, and Cbl-c/Cbl-3 are thought to regulate
      signaling through protein-tyrosine kinases, positively as scaffold proteins and
      negatively as ubiquitin ligases. However, the precise signaling pathways and
      target proteins for each Cbl family member are not well understood. Here we show
      that Src is a preferential target of Cbl-c for degradation. Although exogenous
      expression of all Cbl family proteins suppressed the anchorage-independent growth
      of v-Src-transformed NIH3T3 cells, only Cbl-c caused reversion of the refractile
      morphology. The level of v-Src protein was reduced by Cbl-c, possibly through a
      lysosome-dependent pathway. The TKB domain and RING finger of Cbl-c were
      important for its antioncogenic activity. Wild-type Cbl-c promoted ubiquitination
      of Src in 293T cells, whereas a RING finger mutant did not. Cbl-c bound
      specifically to Src phosphorylated at Tyr419. Furthermore, Cbl-c together with
      UbcH5 induced ubiquitination of Src in vitro. Importantly, the Tyr419
      nonphosphorylated form of Src was not ubiquitinated by Cbl-c. Therefore,
      activated Src may be a direct target of Cbl-c in vivo. Our results suggest that
      Cbl and Cbl-b suppress v-Src-induced transformation through mechanisms distinct
      from that of Cbl-c.

PMID- 14661061
TI  - SU11752 inhibits the DNA-dependent protein kinase and DNA double-strand break
      repair resulting in ionizing radiation sensitization.
AB  - Loss of the DNA-dependent protein kinase (DNA-PK) results in increased
      sensitivity to ionizing radiation due to inefficient repair of DNA double-strand
      breaks. Overexpression of DNA-PK in tumor cells conversely results in resistance
      to ionizing radiation. It is therefore possible that inhibition of DNA-PK will
      enhance the preferential killing of tumor cells by radiotherapy. Available
      inhibitors of DNA-PK, like wortmannin, are cytotoxic and stop the cell cycle
      because they inhibit phoshatidylinositol-3-kinases at 100-fold lower
      concentrations required to inhibit DNA-PK. In an effort to develop a specific DNA
      PK inhibitor, we have characterized SU11752, from a three-substituted indolin-2
      ones library. SU11752 and wortmannin were equally potent inhibitors of DNA-PK. In
      contrast, inhibition of the phoshatidylinositol-3-kinase p110gamma required 500
      fold higher concentration of SU11752. Thus, SU11752 was a more selective
      inhibitor of DNA-PK than wortmannin. Inhibition kinetics and a direct assay for
      ATP binding showed that SU11752 inhibited DNA-PK by competing with ATP. SU11752
      inhibited DNA double-strand break repair in cells and gave rise to a five-fold
      sensitization to ionizing radiation. At concentrations of SU11752 that inhibited
      DNA repair, cell cycle progression was still normal and ATM kinase activity was
      not inhibited. We conclude that SU11752 defines a new class of drugs that may
      serve as a starting point for the development of specific DNA-PK inhibitors.

PMID- 14661062
TI  - Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9
      expression by inhibiting JNK and PKC delta signal transduction.
AB  - Proteolytic degradation of the extracellular matrix and tumor metastasis
      correlate with the expression of endopeptidases known as matrix
      metalloproteinases (MMPs). The expression of MMPs is regulated by cytokines and
      signal transduction pathways, including those activated by phorbol myristate
      acetate (PMA). We found that resveratrol, a phytoalexin present in grapes,
      significantly inhibits the PMA-induced increase in MMP-9 expression and activity.
      These effects of resveratrol are dose dependent and correlate with the
      suppression of MMP-9 mRNA expression levels. PMA caused about a 23-fold increase
      in MMP-9 promoter activity, which was suppressed by resveratrol. Transient
      transfection utilizing MMP-9 constructs, in which specific transcriptional
      factors were mutagenized, indicated that the effects of PMA and resveratrol were
      mediated via an activator protein-1 and nuclear factor-kappaB response element.
      Resveratrol inhibited PMA-mediated activation of c-Jun N-terminal kinase (JNK)
      and protein kinase C (PKC)-delta activation. Therefore, we conclude that the MMP
      9 inhibition activity of resveratrol and its inhibition of JNK and PKC-delta may
      have a therapeutic potential, given that a novel means of controlling growth and
      invasiveness of tumors.

PMID- 14661063
TI  - Expression of both TNF-alpha receptor subtypes is essential for optimal skin
      tumour development.
AB  - Keratinocyte-derived TNF-alpha acts as an endogenous tumour promoter and can also
      regulate AP-1 activity in mouse epidermis. To gain further insight into TNF-alpha
      signalling during skin tumour formation, mice deficient in TNFR1 (TNFR1-/- mice)
      or TNFR2 (TNFR2-/- mice) were subjected to chemical carcinogenesis. Tumour
      multiplicity was significantly reduced in TNFR1-/- and TNFR2-/- mice compared to
      wild-type (wt) mice, suggesting that both receptors have protumour activity.
      However, TNFR1-/- mice were markedly more resistant to tumour development than
      TNFR2-/- mice indicating that TNFR1 is the major mediator of TNF-alpha-induced
      tumour formation. TNFR1 and TNFR2 were both expressed in wt epidermis during
      tumour promotion and by primary keratinocytes in vitro. TPA-induced c-Jun
      expression was transient in TNFR1-/- and TNFR2-/- compared to wt epidermis and
      this was reflected by reduced induction of the AP-1-responsive genes
      granulocyte/macrophage-colony stimulating factor, matrix metalloproteinase-9 and
      matrix metalloproteinase-3. These genes were differentially regulated in TNFR1-/-
      compared to TNFR2-/- epidermis, suggesting that the TNF-alpha receptors act
      independently via different AP-1 complexes to transduce TNF-alpha signals during
      tumour promotion. In addition, TNFR2 cooperated with TNFR1 to optimise TNFR1
      mediated TNF-alpha bioactivity on keratinocytes in vitro. Our data provide
      further insight into TNF-alpha signalling in malignancy and provide some
      rationale for the use of TNF-alpha antagonists in the treatment of cancer.

PMID- 14661064
TI  - Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele
      in an HDGC tumour.
AB  - Mutations in CDH1, encoding E-cadherin, are the underlying genetic defect in
      approximately one-third of the hereditary diffuse gastric cancer (HDGC) families
      described so far. Tumours arising in these families show abnormal or absence of E
      cadherin expression, following the model of tumour suppressor gene inactivation.
      A single study has been reported showing inactivation of the CDH1 wild-type
      allele in tumour cells from HDGC families either by promoter methylation or by
      somatic mutation. In order to find the genetic alteration responsible for the
      presence of diffuse gastric cancers in four members of a Caucasian family, we
      have screened the coding sequence of CDH1 for germline mutations and searched for
      the second inactivating hit in the tumour samples. In this family, we have found
      a germline splice-site mutation in all members affected by gastric cancer and, in
      one tumour, a somatic deletion affecting at least exon 8 of CDH1. Our results
      show that a CDH1 intragenic deletion is the second hit inactivating the wild-type
      allele, in one of the tumours in this family.

PMID- 14661065
TI  - Burst firing in sensory systems.

PMID- 14661066
TI  - Immunity to fungal infections.
AB  - The topic of immunity to fungal infections is of interest to a wide range of
      disciplines, from microbiology to immunology. It is of particular interest in
      terms of therapy of HIV-infected individuals, and patients with cancer or
      individuals who have received transplants. Understanding the nature and function
      of the immune response to fungi is an exciting challenge that might set the stage
      for new approaches to the treatment of fungal diseases, from immunotherapy to
      vaccines. The past decade has witnessed the development of a wide range of new
      approaches to elucidate events that occur at the host-fungus interface.

PMID- 14661067
TI  - Brain capillary perfusion in the spontaneously hypertensive rat during the wake
      sleep cycle.
AB  - Hypertension is accompanied by circulatory changes in the brain and in other
      vascular districts; at disease onset, these changes may be largely functional and
      dependent on metabolic and vegetative drives. The wake-sleep cycle is a major
      physiological source of ultradian variability in autonomic function and in
      cerebral blood flow and metabolism. Aim of the study was to investigate whether
      sleep induces functional changes in the brain microcirculation in the developing
      hypertensive state. The fraction of brain capillaries perfused by plasma
      (perfused/anatomical capillaries) was assessed in young (8-10 weeks)
      spontaneously hypertensive rats (SHR) during quiet wakefulness, quiet sleep and
      active sleep. The density of anatomical capillaries was assessed in two groups of
      animals using both a histochemical method (alkaline phosphatase, AP, for
      morphometric measurements) and an immunofluorescence method (anti-fibronectin
      antibodies, FN, to detect all existing capillaries). The density of perfused
      capillaries was determined by intravascular injection of a fluorescent marker.
      The fraction of anatomical capillaries perfused by plasma was always close to
      maximal (0.96-0.97), without significant variations among the states of the wake
      sleep cycle, and was the same for AP-stained and FN-stained sections. Data thus
      indicate that in this model of essential hypertension no functional changes in
      plasma perfusion of cerebral capillaries occur in the early stages of the
      disease.

PMID- 14661068
TI  - The use of visual feedback and on-line target information in catching and
      grasping.
AB  - Although visual feedback (i.e. seeing our hand while we move it) improves the
      accuracy and efficiency of grasping movements, these positive effects of visual
      feedback are not consistently found for catching. It was the aim of our study to
      compare the efficiency of the use of visual feedback in grasping and catching and
      to explore possible reasons why visual feedback effects have been found less
      consistently in catching than in grasping. The first reason might be technical.
      Less sensitive measurement methods have been used in catching; this might explain
      why some catching studies did not find visual feedback effects. This problem was
      avoided in our study by using the same methods for both the catching and the
      grasping task. The effects of visual feedback were examined under standard
      conditions and under conditions where subjects wore prismatic glasses.
      Nevertheless, visual feedback effects were obtained for grasping but not for
      catching movements. This confirms that the difference in the use of visual
      feedback is real and not due to technical differences between grasping and
      catching studies. The second reason relates to the different temporal demands of
      grasping and catching. During a catching task, subjects have less time to
      respond, and therefore might not have sufficient time to use visual feedback. We
      tested this explanation with a task that required subjects to reach for a
      stationary object (i.e. grasping) as quickly as they had for the moving object in
      the catching task. However, even in this time-constrained grasping task,
      significant visual feedback effects were found, suggesting that time constraints
      do not explain the lack of visual feedback effects in catching. In our last
      explanation, we suggest that possibly the mode of motor control is different for
      catching and grasping, more particularly while grasping allows for on-line
      corrections, such corrections might not be possible for catching movements. We
      tested this explanation with a catching task that contained perturbation trials.
      During those perturbation trials, the target trajectory was shifted, after the
      subject had already started to move. We found that subjects responded to the
      target shifts with an appropriate shift of their catching response. This shows
      that on-line corrections are possible in the case of catching movements. We
      conclude that neither differences in the temporal demands nor in the capacity to
      make on-line modifications explain why visual feedback is used less effectively
      in the catching than in the grasping task.

PMID- 14661069
TI  - Involvement of endogenous endothelins in thermal and mechanical inflammatory
      hyperalgesia in mice.
AB  - Endothelin receptors have been involved in inflammatory, neuropathic and tumoral
      pain. In the case of inflammatory hyperalgesia, some previous papers have pointed
      towards the involvement of ETB receptors, although the stimulation of ETA
      receptors seems to participate in the development of the inflammatory reaction.
      We have studied the effect of ETA and ETB receptor antagonists in the thermal and
      mechanical hyperalgesia induced in a model of acute (induced by carrageenan) and
      chronic (induced by complete Freund's adjuvant, CFA) inflammation in mice. The
      i.pl. administration of the selective ETA antagonist BQ-123 (1-10 nmol)
      antagonized the thermal hyperalgesia detected by the unilateral hot plate test,
      observed in both inflammatory models, whereas the i.pl. administration of the ETB
      selective antagonist BQ-788 (17.7 nmol) failed to modify this. In contrast, both
      BQ-123 (3-17.7 nmol) and BQ-788 (3-17.7 nmol) antagonized the mechanical
      hyperalgesia, as assessed by the Randall-Selitto test in carrageenan- and CFA
      treated mice. Both BQ-123 and BQ-788 were able to antagonize the mechanical
      hyperalgesia induced by ET-1 (200 pmol; i.pl.) in the same dose range. Thus, ETA
      receptors are involved in both thermal and mechanical hyperalgesia whereas ETB
      receptors are only involved in mechanical hyperalgesia in these inflammatory
      models. In conclusion, the role of ETB receptors in inflammatory pain is further
      supported and new insights into the participation of ETA receptors in
      inflammatory hyperalgesia are given.

PMID- 14661070
TI  - Concentrations of the des-F(6)-quinolone garenoxacin in plasma and joint
      cartilage of immature rats.
AB  - Garenoxacin is a des-F(6)-quinolone with a broad antibacterial spectrum, which
      has previously been shown to exhibit low chondrotoxicity in juvenile dogs
      compared with several other quinolones. A study was performed to determine
      whether the low chondrotoxicity observed in immature rats following garenoxacin
      treatment could be explained by poor penetration into cartilage tissue.
      Garenoxacin was orally administered to immature (4- to 5-week-old) Wistar rats as
      a single dose-or as doses given on 5 consecutive days-of 0 (vehicle), 200, 400,
      and 600 mg/kg ( n=5 per dose level). Additional groups of rats were orally dosed
      with 600 mg/kg ofloxacin and ciprofloxacin. One knee joint of each animal (24 h
      after the last dose) was studied histologically after staining with Toluidine
      blue. The pharmacokinetics of garenoxacin in plasma (200, 400, and 600 mg/kg) and
      in knee joint cartilage (200 and 600 mg/kg) was assessed in separate groups of
      rats ( n=55 per dose level). Concentrations of garenoxacin in plasma and
      cartilage were measured using an HPLC method. No signs of chondrotoxicity were
      observed in the immature rats treated with garenoxacin or ciprofloxacin for 5
      days at the doses investigated in this study. However, ofloxacin was found to
      induce cartilage lesions that were typical of those seen for this quinolone.
      Systemic exposure to garenoxacin increased as a function of dose. Across dose and
      study day, mean garenoxacin plasma maximum concentration ( C(max)) and area under
      the concentration-time curve (AUC(tau)) values were in the range 12-26 mg/l and
      33-133 mgxh/l, respectively. Garenoxacin C(max) and AUC were similar on days 1
      and 5, within each dose, indicating the absence of accumulation or reduction in
      the systemic exposure. Values determined for T(max) (0.25-1.0 h) and T(1/2) (3.8
      6.4 h) of garenoxacin in plasma did not vary with dose or study day. Although
      peak garenoxacin concentrations in cartilage were between equal levels to and 2.5
      fold of those found in plasma, the observed ratios were somewhat lower than those
      reported for other quinolones, e.g. ofloxacin or sparfloxacin. Since garenoxacin
      appeared to be well absorbed following oral administration and concentrations in
      cartilage tended to be higher than those in plasma, it is unlikely that the low
      chondrotoxicity in comparison with other quinolones is explained by differences
      in the pharmacokinetics of these compounds.

PMID- 14661071
TI  - Comparison of the sensitivity of different toxicological endpoints in Caco-2
      cells after cadmium chloride treatment.
AB  - The human colorectal adenocarcinoma cell line Caco-2 is a widely used in vitro
      model of the intestinal barrier. Cadmium chloride (CdCl(2)) is a highly toxic
      metal compound, ubiquitous in the biosphere, able to enter the food chain and to
      reach the intestinal epithelium, causing structural and functional damages. The
      aim of this work was to characterise cadmium toxicity in Caco-2 cells and, in
      particular, to compare the sensitivity of different endpoints revealing damage
      both on the epithelial barrier and at the cellular or molecular level. After 24-h
      exposure of the cells to CdCl(2), lactate dehydrogenase (LDH) leakage showed
      cadmium-induced cell toxicity, significant from 25 microM CdCl(2) and above, and
      analysis of different cell death pathways indicated the presence of necrosis
      after treatment with 50 microM CdCl(2). At the molecular level, we observed an
      increase in the protective protein heat shock protein 70 (HSP70), starting at 10
      microM CdCl(2). At the barrier level, transepithelial electrical resistance
      (TEER) decreased while paracellular permeability (PCP) significantly increased
      after the treatment, showing an EC(50) of 6 and 16 microM CdCl(2), respectively,
      and indicating the loss of barrier integrity. In conclusion, our data reveal that
      CdCl(2) toxicity in Caco-2 cells can be detected at the barrier level at very low
      concentrations; also, HSP70 was shown to be a sensitive marker for detecting in
      vitro cadmium-induced toxicity.

PMID- 14661072
TI  - Periprosthetic bone remodelling of two types of uncemented femoral implant with
      proximal hydroxyapatite coating: a 3-year follow-up study addressing the
      influence of prosthesis design and preoperative bone density on periprosthetic
      bone loss.
AB  - Periprosthetic bone loss is a major cause of concern in patients undergoing total
      hip arthroplasty (THA). Further studies are required to identify the factors
      determining the pattern of bone remodelling following THA and obtain improvements
      in the design and durability of prostheses. In this study, we monitored
      periprosthetic bone loss around two different types of hydroxyapatite coated
      femoral implant over a 3-year period to evaluate their design and investigate the
      relationship with the preoperative bone mineral density (BMD) at the spine, hip
      and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46-75 years)
      undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or
      Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry
      (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine,
      the contralateral hip and the non-dominant forearm. Postoperative DXA scans were
      performed to measure periprosthetic BMD at 10 days (treated as baseline), 6
      weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone
      analysis. Results were expressed as the percentage change from baseline and the
      data examined for the differences in bone loss between the different Gruen zones,
      between the ABG and MH stems, and the relationship with preoperative BMD. A total
      of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there
      was a statistically significant BMD decrease in every Gruen zone that varied
      between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the
      MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a
      small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG
      patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone
      in MH patients compared with ABG with the largest difference (10%, P=0.018) in
      Gruen zone 7. Highly significant relationships were found between periprosthetic
      bone loss and preoperative BMD measured at the PA spine ( P<0.001), total hip (
      P=0.004) and total distal radius ( P<0.001). This study showed differences
      between two different designs of hydroxyapatite-coated implant that confirmed
      that prosthesis design influences periprosthetic bone loss. The study also showed
      that patients' bone density measured at the spine, hip or forearm at the time of
      operation was a major factor influencing bone loss around the femoral stem.

PMID- 14661073
TI  - Low bone density and abnormal bone turnover in patients with atherosclerosis of
      peripheral vessels.
AB  - Patients with vascular calcifications often have low bone mineral density (BMD),
      but it is still uncertain if osteoporosis and peripheral vascular disease (VD)
      are interrelated and linked by a common pathomechanism. Moreover, data on bone
      turnover in patients with advanced atherosclerosis are lacking. We measured BMD
      by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS),
      as well as the serum levels of osteocalcin (OC), bone-specific alkaline
      phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary
      concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in
      36 patient (20 male and 16 female) with serious atherosclerotic involvement of
      the carotid and/or femoral artery to investigate the underlying mechanism of
      vascular and osseous disorders. Thirty age-matched and gender matched healthy
      individuals served as controls. After adjustment for age, BMD was significantly
      reduced at the lumbar spine in 23/36 (63%) patients (mean T score -1.71+/-1.42)
      and at the proximal femur in 34/36 (93%) patients (neck mean T score -2.5+/
      0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no
      effect on the relationship between vascular calcification and bone density at any
      site measured. VD subjects had OC and BAP serum levels lower than controls
      (13.3+/-3.1 vs 27.7+/-3.3 ng/ml, P<0.01, and 8.4+/-2.3 vs 12.5+/-1.4 microg/l,
      P<0.01, respectively). Urinary CrossLaps excretion was not significantly
      different in patients with VD and in controls (257.9+/-138.9 vs 272.2+/-79.4
      micro g/mmol Cr, respectively). Serum OPG and RANKL levels were similar in
      patients and in controls (3.5+/-1.07 vs 3.4+/-1.05 pmol/l, and 0.37+/-0.07 vs
      0.36+/-0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in
      VD, with evidence of age and gender independence. Negative bone remodelling
      balance would be a consequence of reduced bone formation, with no apparent
      increased activation of the OPG-RANKL system.

PMID- 14661074
TI  - The influence of tibial fixation on tunnel enlargement after hamstring tendon
      anterior cruciate ligament reconstruction.
AB  - The retrospective study was designed to evaluate tibial-tunnel enlargement after
      anterior cruciate ligament reconstruction with hamstring autograft. Forty-three
      patients (43 knees) were enrolled, among whom a spiked washer was used for the
      tibial side fixation in 20 knees (Group SW) and the WasherLoc was used in 23
      knees (Group WL). After an average 16 (range 12-32) months' follow-up, the
      distance between the sclerotic margins of the tibial tunnel was measured at the
      joint level, and 1 and 2 cm distal to the joint level on the lateral view
      radiographs, from which the tibial-tunnel enlargement at each point (E1, E2, and
      E3 respectively) was determined. Anterior knee laxity was also measured using a
      KT-1000 or KT-2000 arthrometer at follow-up. E1, E2, and E3 were 2.3+/-1.3 mm
      (mean+/-standard deviation), 1.8+/-0.8 mm, and 1.5+/-0.8 mm respectively in Group
      SW, and 2.6+/-1.0 mm, 2.6+/-1.2 mm, and 2.9+/-1.6 mm in Group WL. Group WL had a
      larger mean value than Group SW at each level of measurement, with a
      statistically significant difference in E2 and E3. Fifty percent of the tunnels
      were the cone type in Group SW, whereas reversed cone-type tunnels were the most
      common (39%) in Group WL. The side-to-side difference in anterior knee laxity was
      -0.6+/-5.2 mm in Group SW and 1.8+/-9.0 mm in Group WL, which was significantly
      different between the groups. No statistical relationship was found between
      tunnel enlargement and side-to-side difference in anterior knee laxity in Group
      SW, whereas there was a slight negative correlation between E1 or E2 and anterior
      knee laxity in Group WL. It is possible that there is greater tension applied to
      the graft when the WasherLoc is used, which creates larger compressive forces on
      the posterior wall of the tibial tunnel by the graft. This was probably the
      reason for the greater tunnel enlargement and the high incidence of the reversed
      cone-type tunnel in Group WL.

PMID- 14661075
TI  - Comment on "Changes in cerebral interstitial glycerol concentration in head
      injured patients; correlation with secondary events".

PMID- 14661076
TI  - A physiological and morphological study on the injury caused by exposure to the
      air pollutant, peroxyacetyl nitrate (PAN), based on the quantitative assessment
      of the injury.
AB  - A method for the numerical assessment of the foliar injury caused by the
      photochemical oxidant, peroxyacetyl nitrate (PAN), was devised, using three
      injury indices: fresh weight (FW) loss, decreased photosynthetic pigment content,
      and increased ion leakage, which can be measured using the same leaves. The
      injury indices clearly indicated a larger number of PAN-sensitive leaves and a
      more severe level of injury in the PAN-sensitive variety of Petunia hybrida,
      White Champion (WHITE), compared to the PAN-tolerant variety, Blue Champion
      (BLUE). FW and photosynthetic pigment content decreased correlatively in both
      varieties, but ion leakage increased only in WHITE. Morphological observations
      revealed that ion leakage started concurrently with the start of plasmolysis-like
      symptoms at the mesophyll cells of injured WHITE leaves, whereas FW loss
      corresponded to the shrinkage of cells without loss of their round shape in BLUE
      leaves. PAN injuries measured by the injury indices were markedly increased in
      the presence of light, and the morphological changes following PAN exposure were
      similar to those caused by the superoxide-generating chemical, paraquat. The
      results suggested that PAN injuries indicated by the three injury indices are all
      light-dependent, but are caused through several independent mechanisms.

PMID- 14661077
TI  - Pollen-tube growth pattern and chalazogamy in Casuarina equisetifolia
      (Casuarinaceae).
AB  - For a better understanding of pollen-tube guidance in relation to pollen-pistil
      interaction, we investigated the mode of pollen-tube growth in pistils of
      Casuarina equisetifolia, a monoecious, wind-pollinated species that undergoes
      chalazogamous fertilization. The pistil is bicarpellate, but only one of the two
      carpels develops with two ovules. One of these ovules develops more than four
      embryo sacs. Pistils usually require more than 1 month to reach maturity after
      pollen grains have been deposited on the stigmas. During that period, pollen-tube
      growth proceeds discontinuously in five distinct steps that lead up to
      fertilization: (1) from the stigma to the upper region of the style, (2) from the
      upper region of the style to a septum in the ovary, (3) from the septum to the
      surface of the funiculus, (4) from the funiculus to chalaza in the ovule, and (5)
      from the chalaza to an egg apparatus. Probably because of competitive interaction
      between male and female gametophytes (or ovules), one pollen tube is selected
      from among many during the first step (just before the second step), one ovule
      from the two during the second and third steps, and one embryo sac from more than
      four during the fourth and fifth steps. On the basis of our results, erroneous
      drawings and explanations reported in earlier publications on chalazogamy in
      Casuarinaceae should be brought into question.

PMID- 14661078
TI  - Using denaturing HPLC for SNP discovery and genotyping, and establishing the
      linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8)
      gene.
AB  - All-trans-retinol dehydrogenase (RDH8) is a visual cycle enzyme that reduces all
      trans-retinal to all-trans-retinol. As part of an on-going effort to map genes
      involved in complex eye diseases, myopia in particular, using association
      studies, single nucleotide polymorphisms (SNPs) were identified and linkage
      disequilibrium (LD) pattern was established within and around the RDH8 gene. We
      used denaturing high-performance liquid chromatography (DHPLC) to screen SNPs in
      four DNA pools each consisting of DNA from five individuals and genotyped the
      identified SNPs in 150 Chinese subjects from Hong Kong. Fifteen SNPs were
      identified: seven were common with the minor allele frequency >0.05 and ten were
      novel. Common SNPs were included in LD and haplotype analysis using the ASSOCIATE
      and EH programmes. Four SNPs in the 3' region exhibited significant LD and formed
      a haplotype block, while three common SNPs in the 5' region did not exhibit
      useful LD. The LD pattern around the RDH8 gene suggested that one SNP from the
      3'region and two to three SNPs from the 5' region were needed in association
      studies involving RDH8. Our results demonstrated the efficiency of DHPLC in
      screening SNPs when coupled with DNA pooling strategy and in genotyping SNPs.

PMID- 14661079
TI  - Hypercholesterolemia associated with splice-junction variation of inter-alpha
      trypsin inhibitor heavy chain 4 (ITIH4) gene.
AB  - Factors predisposing to the phenotypic features of higher total cholesterol (T
      Cho) have not been clearly defined. Here we report an association between a C/T
      single nucleotide polymorphism at IVS17+8 in the inter-alpha-trypsin inhibitor
      heavy chain 4 gene (ITIH4) and plasma total cholesterol levels in 351 adult
      individuals from an east-central area of Japan. Age and gender-adjusted levels of
      plasma T-Cho, LDL-cholesterol, triglyceride, and HDL-cholesterol were analyzed.
      When we separate the subjects into two genotypic groups regarding this single
      nucleotide polymorphism (SNP), those who lack the T-allele had significantly
      higher plasma T-Cho levels than the others who bear T-allele (mean 252.3 mg/dl
      versus 241.7 mg/dl; p=0.009). Of the 309 individuals without the T-allele,
      approximately 90% presented with hypercholesterolemia, whereas only 10% were
      hypercholesterolemic among 42 individuals with the T-allele (p <0.0001). These
      data suggest that genetic variation at ITIH4 locus is one of the likely candidate
      determinants for plasma cholesterol metabolisms.

PMID- 14661080
TI  - CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common
      polymorphism.
AB  - We found that a subject with Cockayne syndrome type A was a compound heterozygote
      for two new mutations in CKN1 (MIM 216400): a missense mutation (A205P) and a
      nonsense (E13X) mutation. We also identified and characterized a new common
      single nucleotide polymorphism in CKN1 in five groups.

PMID- 14661081
TI  - Interfacial adaptation of a calcium aluminate cement used in class II cavities,
      in vivo.
AB  - The aim of this in vivo study was to evaluate the interfacial marginal adaptation
      of a calcium aluminate cement, Doxadent (DD), and to compare it intra
      individually with a resin composite, Tetric Ceram/Syntac Single-Component
      (TC/SS), in Class II cavities. Sixteen Class II box-shaped, enamel-bordered
      cavities were prepared in eight premolars scheduled to be extracted after 1
      month's service for orthodontic reasons. The interfacial marginal adaptation
      (internal surfaces) of the restorations was evaluated by a quantitative scanning
      electron microscope analysis using a replica method. DD showed a statistically
      significant, lower degree of gap-free adaptation to enamel compared with TC/SS:
      84% vs. 93%. To dentin, DD showed a significantly better adaptation than TC/SS:
      72% vs. 49%. A high frequency of enamel fractures perpendicular to the margins
      was observed for the DD restorations, which may be explained by an expansion of
      the calcium-aluminate cement. It can be concluded that DD showed a better
      adaptation to dentin while TC/SS showed a better adaptation to enamel. The
      dimensional changes of DD have to be investigated before clinical use can be
      recommended.

PMID- 14661082
TI  - Phenomenological and molecular models of biological proton transfers.
AB  - In this paper, the main models describing the transfer of a proton in a molecular
      system are presented. Models valid when the intersite coupling is weak (non
      adiabatic and electronically adiabatic regimes) and strong (adiabatic regime) are
      described. We distinguish molecular models in which the rate constant is obtained
      by considering explicitly various degrees of freedom of the system and simpler,
      phenomenological models built to account for the kinetic isotope effect. The
      relations between the various models are discussed. Their application to specific
      systems is illustrated by several studies reported in the literature, with a
      special emphasis on biological systems.

PMID- 14661084
TI  - Free radical-mediated oxidation of free amino acids and amino acid residues in
      proteins.
AB  - We summarize here results of studies designed to elucidate basic mechanisms of
      reactive oxygen (ROS)-mediated oxidation of proteins and free amino acids. These
      studies have shown that oxidation of proteins can lead to hydroxylation of
      aromatic groups and aliphatic amino acid side chains, nitration of aromatic amino
      acid residues, nitrosylation of sulfhydryl groups, sulfoxidation of methionine
      residues, chlorination of aromatic groups and primary amino groups, and to
      conversion of some amino acid residues to carbonyl derivatives. Oxidation can
      lead also to cleavage of the polypeptide chain and to formation of cross-linked
      protein aggregates. Furthermore, functional groups of proteins can react with
      oxidation products of polyunsaturated fatty acids and with carbohydrate
      derivatives (glycation/glycoxidation) to produce inactive derivatives. Highly
      specific methods have been developed for the detection and assay of the various
      kinds of protein modifications. Because the generation of carbonyl derivatives
      occurs by many different mechanisms, the level of carbonyl groups in proteins is
      widely used as a marker of oxidative protein damage. The level of oxidized
      proteins increases with aging and in a number of age-related diseases. However,
      the accumulation of oxidized protein is a complex function of the rates of ROS
      formation, antioxidant levels, and the ability to proteolytically eliminate
      oxidized forms of proteins. Thus, the accumulation of oxidized proteins is also
      dependent upon genetic factors and individual life styles. It is noteworthy that
      surface-exposed methionine and cysteine residues of proteins are particularly
      sensitive to oxidation by almost all forms of ROS; however, unlike other kinds of
      oxidation the oxidation of these sulfur-containing amino acid residues is
      reversible. It is thus evident that the cyclic oxidation and reduction of the
      sulfur-containing amino acids may serve as an important antioxidant mechanism,
      and also that these reversible oxidations may provide an important mechanism for
      the regulation of some enzyme functions.

PMID- 14661085
TI  - Recent advances in the analysis of oxidized proteins.
AB  - Glutamic semialdehyde is a product of oxidation of arginine and proline, and
      aminoadipic semialdehyde, of oxidation of lysine. These two carbonyl-containing
      compounds are the main carbonyl products of metal-catalyzed oxidation of
      proteins, accounting for 55-100% of the total carbonyl value. Accordingly, they
      are quantitatively very important contributors to the total value of protein
      carbonyls in tissues as measured by the classic spectophotometric assay.
      Sensitive gas chromatography-mass spectrometry based analytical methods allow
      their quantitation in a variety of biological samples, including tissue protein,
      cell cultures and lipoproteins. These measurements provide specific information
      on the oxidative status of proteins that is complementary to that afforded by
      protein carbonyls, and will be useful tools in the ongoing effort to define and
      assess the role of protein oxidation in pathology and aging.

PMID- 14661086
TI  - Tyrosine oxidation products: analysis and biological relevance.
AB  - Dityrosine is found in several proteins as a product of UV irradiation, gamma
      irradiation, aging, exposure to oxygen free radicals, nitrogen dioxide,
      peroxynitrite, and lipid hydroperoxides. Interest of dityrosine in proteins is
      based on its potential as a specific marker for oxidatively damaged proteins and
      their selective proteolysis, hence it could be used as a marker for oxidative
      stress. Dityrosine is also the product of normal post-translational processes
      affecting specific structural proteins. Since post-translational modification of
      a given amino acid in a protein is equivalent to the substitution of that residue
      by an analogue, it has been proposed that the covalent modification of amino
      acids may serve as a "marking" step for protein degradation.

PMID- 14661087
TI  - Dityrosine as a product of oxidative stress and fluorescent probe.
AB  - Dityrosine can be a natural component of protein structure, a product of
      environmental stress, or a product of in vitro protein modification. It is both a
      cross-link and a fluorescent probe that reports structural and functional
      information on the cross-linked protein molecule. Diverse reactions produce
      tyrosyl radicals, which in turn may couple to yield dityrosine. Identification
      and quantitation of dityrosine in protein hydrolysates usually employs reversed
      phase high pressure liquid chromatography (RP-HPLC) or gas chromatography. RP
      HPLC of protein hydrolysates that have been derivatized with dabsyl chloride
      gives a complete amino acid analysis that includes dityrosine and 3
      nitrotyrosine. Calmodulin, which contains a single pair of tyrosyl residues,
      undergoes both photoactivated and enzyme-catalyzed dityrosine formation.
      Polarization measurements, employing the intrinsic fluorescence of dityrosine,
      and catalytic activity determinations show how different patterns of inter- and
      intramolecular cross-linking affect the interactions of calmodulin with Ca(2+)
      and enzymes.

PMID- 14661088
TI  - Histidine and lysine as targets of oxidative modification.
AB  - Histidine and lysine are two representative targets of oxidative modifications.
      Histidine is extremely sensitive to a metal-catalyzed oxidation, generating 2-oxo
      histidine and its ring-ruptured products, whereas the oxidation of lysine
      generates carbonyl products, such as aminoadipic semialdehyde. On the other hand,
      both histidine and lysine are nucleophilic amino acids and therefore vulnerable
      to modification by lipid peroxidation-derived electrophiles, such as 2-alkenals,
      4-hydroxy-2-alkenals, and ketoaldehydes, derived from lipid peroxidation.
      Histidine shows specific reactivity toward 2-alkenals and 4-hydroxy-2-alkenals,
      whereas lysine is a ubiquitous target of aldehydes, generating various types of
      adducts. Covalent binding of reactive aldehydes to histidine and lysine is
      associated with the appearance of carbonyl reactivity and antigenecity of
      proteins.

PMID- 14661089
TI  - Hypochlorite-induced oxidation of amino acids, peptides and proteins.
AB  - Activated phagocytes generate the potent oxidant hypochlorite (HOCl) via the
      release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is known to
      react with a number of biological targets including proteins, DNA, lipids and
      cholesterol. Proteins are likely to be major targets for reaction with HOCl
      within a cell due to their abundance and high reactivity with HOCl. This review
      summarizes information on the rate of reaction of HOCl with proteins, the nature
      of the intermediates formed, the mechanisms involved in protein oxidation and the
      products of these reactions. The predicted targets for reaction with HOCl from
      kinetic modeling studies and the consequences of HOCl-induced protein oxidation
      are also discussed.

PMID- 14661090
TI  - Maillard reaction products in tissue proteins: new products and new perspectives.
AB  - The chemical modification of protein by nonenzymatic browning or Maillard
      reactions increases with age and in disease. Maillard products are formed by
      reactions of both carbohydrate- and lipid-derived intermediates with proteins,
      leading to formation of advanced glycation and lipoxidation end-products
      (AGE/ALEs). These modifications and other oxidative modifications of amino acids
      increase together in proteins and are indicators of tissue aging and pathology.
      In this review, we describe the major pathways and characteristic products of
      chemical modification of proteins by carbohydrates and lipids during the Maillard
      reactions and identify major intersections between these pathways. We also
      describe a new class of intracellular sulfhydryl modifications, Cys-AGE/ALEs,
      that may play an important role in regulatory biology and represent a primitive
      link between nonenzymatic and enzymatic chemistry in biological systems.

PMID- 14661091
TI  - Scavenger receptors for oxidized and glycated proteins.
AB  - Our present knowledge on chemically modified proteins and their receptor systems
      is originated from a proposal by Goldstein and Brown in 1979 for the receptor for
      acetylated LDL which is involved in foam cell formation, one of critical steps in
      atherogenesis. Subsequent extensive studies using oxidized LDL (OxLDL) as a
      representative ligand disclosed at least 11 different scavenger receptors which
      are collectively categorized as "scavenger receptor family". Advanced glycation
      endproducts (AGE) and their receptor systems have been studied independently
      until recent findings that AGE-proteins are also recognized as active ligands by
      scavenger receptors including class A scavenger receptor (SR-A), class B
      scavenger receptors such as CD36 and SR-BI, type D scavenger receptor (LOX-1) and
      FEEL-1/FEEL-2. Three messages can be summarized from these experiments; (i)
      endocytic uptake of OxLDL and AGE-proteins by macrophages or macrophage-derived
      cells is mainly mediated by SR-A and CD36, which is an important step for foam
      cell formation in the early stage of atherosclerosis, (ii) selective uptake of
      cholesteryl esters of high density lipoprotein (HDL) mediated by SR-BI is
      inhibited by AGE-proteins, suggesting a potential pathological role of AGE in a
      HDL-mediated reverse cholesterol transport system, (iii) a novel scavenger
      receptor is involved in hepatic clearance of plasma OxLDL and AGE-proteins.

PMID- 14661092
TI  - Peroxynitrite reactivity with amino acids and proteins.
AB  - Peroxynitrite, the product of the fast reaction between nitric oxide ((*)NO) and
      superoxide O(2)(*-) radicals, is an oxidizing and nitrating agent which is able
      to traverse biological membranes. The reaction of peroxynitrite with proteins
      occurs through three possible pathways. First, peroxynitrite reacts directly with
      cysteine, methionine and tryptophan residues. Second, peroxynitrite reacts fast
      with transition metal centers and selenium-containing amino acids. Third,
      secondary free radicals arising from peroxynitrite homolysis such as hydroxyl and
      nitrogen dioxide, and the carbonate radical formed in the presence of carbon
      dioxide, react with protein moieties too. Nitration of tyrosine residues is being
      recognized as a marker of the contribution of nitric oxide to oxidative damage.
      Peroxynitrite-dependent tyrosine nitration is likely to occur through the initial
      reaction of peroxynitrite with carbon dioxide or metal centers leading to
      secondary nitrating species. The preferential protein targets of peroxynitrite
      and the role of proteins in peroxynitrite detoxifying pathways are discussed.

PMID- 14661093
TI  - Nitric oxide and cell signaling: modulation of redox tone and protein
      modification.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have an impact
      on many cellular processes, often serving as signal transducers in both
      physiological and pathological situations. These small molecules can act as
      ligands for receptors as is the case for nitric oxide and guanylate cyclase.
      However, they can also modify proteins, changing their function and establishing
      a baseline for other signals in a process that we have termed "redox tone." In
      this review, we discuss the different mechanisms of redox cell signaling, and
      give specific examples of RNS participation in cell signaling via classical and
      redox tone pathways.

PMID- 14661094
TI  - Thiolation and nitrosation of cysteines in biological fluids and cells.
AB  - Thiols (RSH) are potent nucleophilic agents, the rates of which depend on the pKa
      of the sulfhydryl. Unlike compounds having other nucleophile moieties (-OH or 
      NH(2)), RSH are involved in reactions, such as conjugations, redox and exchange
      reactions. Although protein SH groups (PSH) react like non-protein thiols (NPSH),
      the biochemistry of proteins is much more complex for reasons such as steric
      hindrance, charge distribution and accessibility of PSH to the solvent (protein
      conformation). The reaction rates and types of end-products of PSH vary a lot
      from protein to protein. The biological problem is even more complex because in
      all compartments and tissues, there may be specific competition between thiols
      (namely between GSH and PSH), regulated by the properties of antioxidant enzymes.
      Moreover, PSH are divided biologically into essential and non-essential and their
      respective influence in the various biological systems is unknown. It follows
      that during phenomena eliciting a prompt thiol response (oxidative stress), the
      antioxidant PSH response and reaction mechanisms vary considerably from case to
      case. For example, in spite of a relatively low pKa that should guarantee good
      antioxidant capacity, PSH of albumin has much less propensity to form adducts
      with conjugating agents than NPSH; moreover, the structural characteristics of
      the protein prevent albumin from forming protein disulfides when exposed to
      oxidants (whereas protein-thiol mixed disulfides are formed in relative
      abundance). On the other hand, proteins with a relatively high reactivity, such
      rat hemoglobin, have much greater antioxidant capacity than GSH, but although
      human hemoglobin has a pKa similar to GSH, for structural reasons it has less
      antioxidant capacity than GSH. When essential PSH are involved in S-thiolation
      and S-nitrosation reactions, a similar change in biological activity is observed.
      S-thiolated proteins are a recurrent phenomenon in oxidative stress elicited by
      reactive oxygen species (ROS). This event may be mediated by disulfides, that
      exchange with PSH, or by the protein intermediate sulfenic acid that reacts with
      thiols to form protein-mixed disulfides. During nitrosative stress elicited by
      reactive nitrogen species (RNS), depending on the oxygen concentration of the
      system, nitrosation reactions of thiols may also be accompanied by protein S
      thiolation. In this review we discuss a number of cell processes and biochemical
      modifications of enzymes that indicate that S-thiolation and S-nitrosation may
      occur simultaneously in the same protein in the presence of appropriate
      interactions between ROS and RNS.

PMID- 14661095
TI  - Peroxynitrite-dependent modifications of tyrosine residues in hemoglobin.
      Formation of tyrosyl radical(s) and 3-nitrotyrosine.
AB  - Although peroxynitrite is believed to be one of the most efficient tyrosine
      nitrating species of biological relevance so far identified, its nitration
      efficiency is nevertheless limited. In fact, the nitrating species formed through
      peroxynitrite decay are caged radicals ((*)OH/(*)NO(2) or, in the presence of
      carbon dioxide, CO(3)(*-)/(*)NO(2)) and the fraction that escapes from the
      solvent cage does not exceed 30-35%. One exception may be represented by metal
      containing compounds that can enhance the formation of nitrotyrosine through a
      bimolecular reaction with peroxynitrite. Moreover, if the metal is also
      regenerated in the reaction, the compound is considered a nitration catalysts and
      the yield of tyrosine nitration enhanced several fold. Examples of peroxynitrite
      dependent nitration catalysts are the Mn-superoxide dismutase, some cytochromes
      and several metalloporphyrins. On the contrary, it has been claimed that some
      hemoproteins are scavengers of peroxynitrite and play a role in limiting its
      biodamaging and bioregulatory activity. In this review, we discuss the case of
      hemoglobin, which is probably the major target of peroxynitrite in blood. This
      protein has been reported to protect intracellular and extracellular targets from
      peroxynitrite-mediated tyrosine nitration. This property is shared with myoglobin
      and cytochrome c. The possible mechanisms conferring to these proteins a
      peroxynitrite scavenging role are discussed.

PMID- 14661096
TI  - A review of approaches to the analysis of 3-nitrotyrosine.
AB  - Our understanding of in vivo tyrosine nitration has been confounded by problems
      associated with the analytical approaches that have been employed to quantify 3
      nitroyrosine (3-NT). Trace analysis is a demanding task under the best of
      circumstances, but 3-NT offers some special concerns. This review examines some
      of these concerns and discusses approaches to ensuring that carefully validated
      analytical data are generated.

PMID- 14661097
TI  - Amino acid and protein oxidation in cardiovascular disease.
AB  - Substantial evidence suggests that oxidative events contribute to the
      pathogenesis of atherosclerotic heart disease. For example, animal model data and
      numerous in vitro studies point to specific pathways as participants in disease
      initiation and progression. Moreover, recent clinical studies demonstrate
      clinical utility in monitoring systemic levels of protein-bound nitrotyrosine as
      a predictor of risk for coronary artery disease, atherosclerotic burden, and
      response to statin therapy. However, a definitive cause-and-effect relationship
      between oxidation and atherosclerosis has yet to be established, and multiple
      recent large prospective "antioxidant" intervention trials have failed to
      significantly impact upon disease risk and progression. In this review we
      highlight why such failures should not be taken as an indictment of the
      "Oxidation Hypothesis." Emphasis will be placed on discussion of molecular
      markers whose structures convey information about oxidation pathways leading to
      their formation, and which appear to be mechanistically linked to the disease
      process. Only through rational design of targeted interventions aimed at
      suppressing distinct oxidation pathways, with concomitant monitoring of
      antioxidant efficacy in human clinical studies, will answers to the role of
      oxidation in the pathogenesis of human atherosclerosis be defined.

PMID- 14661098
TI  - Protein oxidation at the air-lung interface.
AB  - Whilst performing its normal functions the lung is required to deal with a range
      of toxic insults. Whether these are infectious agents, allergens or air
      pollutants they subject the lung to a range of direct and indirect oxidative
      stresses. In many instances these challenges lead to oxidative alterations of
      peptides and proteins within the lung. Measurement of protein oxidation products
      permits the degree of oxidative stress to be assessed and indicates that
      endogenous antioxidant defences are overwhelmed. The range of protein oxidation
      products observed is diverse and the nature and extent of specific oxidation
      products may inform us about the nature of the damaging ROS and NOS. Recently,
      there has been a significant shift away from the measurement of these oxidation
      products simply to establish the presence of oxidative stress, to a focus on
      identifying specific proteins sensitive to oxidation and establishing the
      functional consequences of these modifications. In addition the identification of
      specific enzyme systems to repair these oxidative modifications has lead to the
      belief that protein function may be regulated through these oxidation reactions.
      In this review we focus primarily on the soluble protein components of within the
      surface liquid layer in the lung and the consequence of their undue oxidation.

PMID- 14661099
TI  - Protein oxidation in aging: endoplasmic reticulum as a target.
AB  - Oxidatively modified proteins have been shown to correlate with the age of an
      organism or its tissues. An increase in tissue-susceptibility to experimentally
      induced protein oxidation not only depends on tissue type and age, but also on
      the maximum lifespan potential of the species. A general, although tissue
      dependent, decline in anti-oxidative defenses during aging may very well be
      responsible for this difference in vulnerability. In addition, the level of
      protein modifications also depends on the nature and the subcellular localization
      of the proteins involved. Damage to the endoplasmic reticulum (ER), and its
      subsequent impaired functionality may be involved in the process of aging. This
      is suggested by; (1) an upregulation of ER stress-response chaperones, (2) a
      preferential oxidation of ER-resident proteins and, (3) a disturbance of calcium
      homeostasis. Therefore, this review will focus on the putative involvement of the
      oxidized endoplasmic reticulum in the process of aging.

PMID- 14661100
TI  - Homocysteine and oxidative stress.
AB  - Hyperhomocysteinemia is an independent risk factor for cardiovascular disease
      (ischemic disease, such as stroke and myocardial infarction, and arterial and
      venous thrombotic events) in the general population. We can assume that the
      association is causal, based on the example of homocystinuria, and on the
      evidence put forward by several basic science and epidemiological studies;
      however, the results of large intervention trials, which will grant further
      support to this hypothesis, are not yet available. In addition, the mechanisms
      underlying this relationship, and also explaining the several toxic effects of
      homocysteine, related or not to cardiovascular disease, are unclear. Oxidation is
      one of the most favored postulated mechanisms; others are nitrosylation,
      acylation, and hypomethylation. Regarding the relative importance of these
      mechanisms, each of these hold pros and cons, and these are weighed in order to
      propose a balance of evidence.

PMID- 14661101
TI  - Proteomics for the identification of specifically oxidized proteins in brain:
      technology and application to the study of neurodegenerative disorders.
AB  - Proteomics offers the opportunity elucidate the complex protein interactions of
      cellular systems by studying the products of genes, i.e., proteins, and their
      structure, function and localization. The purpose of proteomics is to explain the
      information contained in the genome sequences in order to provide clues on
      cellular events, especially related to disease. Our proteomic approach has made
      possible the identification of specifically oxidized proteins in Alzheimer's
      disease (AD) brain, providing for the first time evidence on how oxidative stress
      plays a crucial role in AD-related neurodegeneration. This represents an example
      of the use of proteomics to solve biological problems related to disease. The
      field, which is still in its infancy, represents a very promising way to
      elucidate mechanism of disease at a protein level. However, the techniques that
      support its development present several limitations and require introduction of
      new tools and innovation in order to achieve a fast, reliable and sensitive
      method to understand normal biological processes and their regulation as well as
      these cellular properties in disease.

PMID- 14661102
TI  - Relevance of protein nitration in brain injury: a key pathophysiological
      mechanism in neurodegenerative, autoimmune, or inflammatory CNS diseases and
      stroke.
AB  - This review has focused on the evidence for the involvement of nitrative
      oxidation in certain neurodegenerative disorders (Parkinson's Disease,
      Alzheimer's Disease, Amyotrophic Lateral Sclerosis), stroke, and inflammatory and
      autoimmune disorders (with particular attention devoted to multiple sclerosis).
      The relationship between protein peroxidation and pathological changes observed
      in the above disorders has been reported. Whereas many of the findings are from
      studies with animal models and autoptic specimens from human patients, few data
      are available from cerebrospinal fluid and blood samples of the patients at
      different times and disease stages. The participation of nitrative oxidation to
      the direct and indirect injury of neurons and other cells of the brain (i.e.,
      oligodendrocytes, for multiple sclerosis) is clear; less evident is their
      relevance for the development and progression of these disorders.Further studies
      should be aimed to establish the clinical and prognostic value of peroxidative
      markers for the CNS diseases considered. This is fundamental for the development
      of therapeutic interventions antagonizing nitric oxide-related species damage.

PMID- 14661103
TI  - Redox regulation of heat shock protein expression in aging and neurodegenerative
      disorders associated with oxidative stress: a nutritional approach.
AB  - Oxidative stress has been implicated in mechanisms leading to neuronal cell
      injury in various pathological states of the brain. Alzheimer's disease (AD) is a
      progressive disorder with cognitive and memory decline, speech loss, personality
      changes and synapse loss. Many approaches have been undertaken to understand AD,
      but the heterogeneity of the etiologic factors makes it difficult to define the
      clinically most important factor determining the onset and progression of the
      disease. However, increasing evidence indicates that factors such as oxidative
      stress and disturbed protein metabolism and their interaction in a vicious cycle
      are central to AD pathogenesis. Brains of AD patients undergo many changes, such
      as disruption of protein synthesis and degradation, classically associated with
      the heat shock response, which is one form of stress response. Heat shock
      proteins are proteins serving as molecular chaperones involved in the protection
      of cells from various forms of stress.Recently, the involvement of the heme
      oxygenase (HO) pathway in anti-degenerative mechanisms operating in AD has
      received considerable attention, as it has been demonstrated that the expression
      of HO is closely related to that of amyloid precursor protein (APP). HO induction
      occurs together with the induction of other HSPs during various
      physiopathological conditions. The vasoactive molecule carbon monoxide and the
      potent antioxidant bilirubin, products of HO-catalyzed reaction, represent a
      protective system potentially active against brain oxidative injury. Given the
      broad cytoprotective properties of the heat shock response there is now strong
      interest in discovering and developing pharmacological agents capable of inducing
      the heat shock response. Increasing interest has been focused on identifying
      dietary compounds that can inhibit, retard or reverse the multi-stage
      pathophysiological events underlying AD pathology. Alzheimer's disease, in fact,
      involves a chronic inflammatory response associated with both brain injury and
      beta-amyloid associated pathology. All of the above evidence suggests that
      stimulation of various repair pathways by mild stress has significant effects on
      delaying the onset of various age-associated alterations in cells, tissues and
      organisms. Spice and herbs contain phenolic substances with potent antioxidative
      and chemopreventive properties, and it is generally assumed that the phenol
      moiety is responsible for the antioxidant activity. In particular, curcumin, a
      powerful antioxidant derived from the curry spice turmeric, has emerged as a
      strong inducer of the heat shock response. In light of this finding, curcumin
      supplementation has been recently considered as an alternative, nutritional
      approach to reduce oxidative damage and amyloid pathology associated with AD.
      Here we review the importance of the heme oxygenase pathway in brain stress
      tolerance and its significance as an antidegenerative mechanism potentially
      important in AD pathogenesis. These findings have offered new perspectives in
      medicine and pharmacology, as molecules inducing this defense mechanism appear to
      be possible candidates for novel cytoprotective strategies. In particular,
      manipulation of endogenous cellular defense mechanisms such as the heat shock
      response, through nutritional antioxidants or pharmacological compounds,
      represents an innovative approach to therapeutic intervention in diseases causing
      tissue damage, such as neurodegeneration. Consistent with this notion,
      maintenance or recovery of the activity of vitagenes, such as the HO gene,
      conceivably may delay the aging process and decrease the occurrence of age
      related neurodegenerative diseases.

PMID- 14661104
TI  - A new skin-surface device for measuring the curvature and global and segmental
      ranges of motion of the spine: reliability of measurements and comparison with
      data reviewed from the literature.
AB  - There is an increasing awareness of the risks and dangers of exposure to
      radiation associated with repeated radiographic assessment of spinal curvature
      and spinal movements. As such, attempts are continuously being made to develop
      skin-surface devices for use in examining the progression and response to
      treatment of various spinal disorders. However, the reliability and validity of
      measurements recorded with such devices must be established before they can be
      recommended for use in the research or clinical environment. The aim of this
      study was to examine the reliability of measurements using a newly developed skin
      surface device, the Spinal Mouse. Twenty healthy volunteers (mean age 41 +/- 12
      years, nine males, 11 females) took part. On 2 separate days, spinal curvature
      was measured with the Spinal Mouse during standing, full flexion, and full
      extension (each three times by each of two examiners). Paired t-tests, intraclass
      correlation coefficients (ICC), and standard errors of measurement (SEM) with 95%
      confidence intervals were used to characterise between-day and interexaminer
      reliability for: standing sacral angle, lumbar lordosis, thoracic kyphosis, and
      ranges of motion (flexion, extension) of the thoracic spine, lumbar spine, hips,
      and trunk. The between-day reliability for segmental ranges of flexion was also
      determined for each motion segment from T1-2 to L5-S1. The majority of parameters
      measured for the 'global regions' (thoracic, lumbar, or hips) showed good between
      day reliability. Depending on the parameter of interest, between-day ICCs ranged
      from 0.67 to 0.92 for examiner 1 (average 0.82) and 0.57 to 0.95 for examiner 2
      (average 0.83); for 70% of the parameters measured, the ICCs were greater than
      0.8 and generally highest for the lumbar spine and whole trunk measures. For
      lumbar spine range of flexion, the SEM was approximately 3 degrees. The ICCs were
      also good for the interexaminer comparisons, ranging from 0.62 to 0.93 on day 1
      (average 0.81) and 0.70 to 0.94 on day 2 (average 0.86), although small
      systematic differences were sometimes observed in their mean values. The latter
      were still evident even if both examiners used the same skin markings. For
      segmental ranges of flexion, the ICCs varied between vertebral levels but overall
      were lower than for the global measures (average for all levels in all analyses,
      ICC 0.6). For each examiner, the average between-day SEM over all vertebral
      levels was approximately 2 degrees. For 'global' regions of the spine, the Spinal
      Mouse delivered consistently reliable values for standing curvatures and ranges
      of motion which compared well with those reported in the literature. This
      suggests that the device can be reliably implemented for in vivo studies of the
      sagittal profile and range of motion of the spine. As might be expected for the
      smaller angles being measured, the segmental ranges of flexion showed lower
      reliability. Their usefulness with regard to the interpretation of individual
      results and the detection of 'real change' on an individual basis thus remains
      questionable. Nonetheless, the group mean values showed few between-day
      differences, suggesting that the device may still be of use in providing
      clinically interesting data on segmental motion when examining groups of
      individuals with a given spinal pathology or undergoing some type of
      intervention.

PMID- 14661106
TI  - Density-range size relationships in French riverine fishes.
AB  - We examined the relation between the local density of species and the size of the
      geographic range for French riverine fishes. As for most other taxonomic groups,
      a positive interspecific relationship is found for this group. This relationship
      is robust to the confounding effects of phylogeny and is not a priori a product
      of other potential mechanistic artefacts. We formally tested two of the principal
      biological mechanisms already proposed (i.e. the niche breadth hypothesis and the
      resource availability hypothesis). We found no support for the niche breadth
      hypothesis. In contrast, we found consistent support for the closely related
      resource availability hypothesis. Species utilising resources (habitats) that are
      marginal tend to appear at low density and to have narrow distribution whereas
      species utilising widespread habitats tend to be more abundant and more widely
      distributed. Using data on body size and reproductive traits we explored the
      potential influence of these variables in explaining significant variation around
      the density-range size relationship. Only body size explains significant
      variation around the relationship, being negatively correlated with local density
      and positively correlated with range size.

PMID- 14661105
TI  - Uptake of cadmium from an experimentally contaminated calcareous soil by
      arbuscular mycorrhizal maize (Zea mays L.).
AB  - We investigated uptake of Cd by arbuscular mycorrhizal (AM) maize inoculated with
      Glomus mosseae from a low-P sandy calcareous soil in two glasshouse experiments.
      Plants grew in pots containing two compartments, one for root and hyphal growth
      and one for hyphal development only. Three levels of Cd (0, 25 and 100 mg kg(-1))
      and two of P (20 and 60 mg kg(-1)) were applied separately to the two
      compartments to assess hyphal uptake of Cd. Neither Cd nor P addition inhibited
      root colonization by the AM fungus, but Cd depressed plant biomass. Mycorrhizal
      colonization, P addition and increasing added Cd level led to lower Cd
      partitioning to the shoots. Plant P uptake was enhanced by mycorrhizal
      colonization at all Cd levels studied. When Cd was added to the plant compartment
      and P to the hyphal compartment, plant biomass increased with AM colonization and
      the mycorrhizal effect was more pronounced with increasing Cd addition. When P
      was added to the plant compartment and Cd to the hyphal compartment, plant
      biomass was little affected by AM colonization, but shoot Cd uptake was increased
      by colonization at the low Cd addition rate (25 mg kg(-1)) and lowered at the
      higher Cd rate (100 mg kg(-1)) but with no difference in root Cd uptake. These
      effects may have been due to immobilization of Cd by the fungal mycelium or
      effects of the AM fungus on rhizosphere physicochemical conditions and are
      discussed in relation to possible phytostabilization of contaminated sites by AM
      plants.

PMID- 14661107
TI  - Changes in the expression pattern of the plasma membrane H+-ATPase in developing
      Ricinus communis cotyledons undergoing the sink/source transition.
AB  - The plasma membrane (PM) H+-ATPase is thought to play a key role in generating
      the proton motive force used to drive the uptake and accumulation of solutes in
      plant cells. Changes in its expression pattern were studied in the Ricinus
      communis L. cotyledon as it changed from a sink to a source organ. Expression was
      monitored in 3-, 10- and 14-day-old cotyledons using an antibody to the maize PM
      H+-ATPase. The antibody labelled a 100-kDa protein in membrane fractions prepared
      from cotyledons and this protein occurred at higher levels in the PM-enriched
      fractions compared to those enriched in intracellular membranes. Immunostaining
      of tissue sections of 3-day-old Ricinus cotyledons (sinks) with this antibody
      demonstrated that the PM H+-ATPase was highly expressed in the lower epidermal
      cells and also in the vascular bundles, particularly the phloem. The high
      expression in the epidermis suggests that these cells may be important in the
      initial active uptake of solutes from the endosperm. A similar distribution was
      observed in the 10-day-old seedlings but, in addition, larger, more spherical
      cells (idioblasts) had developed in the lower and upper epidermal layers and
      these were also labelled. In 14-day-old seedlings the cotyledons are no longer
      reliant on nutrients from the endosperm (which has totally degraded) and they are
      functioning as source organs. This is reflected in a decrease in PM H+-ATPase
      expression in the lower epidermal cells, apart from idioblasts and stomatal guard
      cells. The latter were also observed in the upper epidermis. Expression remained
      high in the vascular bundles of 14-day-old seedlings with strong staining in the
      phloem.

PMID- 14661108
TI  - Biosynthesis of pectic galactan by membrane-bound galactosyltransferase from
      soybean ( Glycine max Merr) seedlings.
AB  - We investigated the properties of a galactosyltransferase (GalT) that is involved
      in the synthesis of beta-(1-->4)-galactan side chains of pectins. A membrane
      preparation of etiolated 6-day-old soybean ( Glycine max Merr.) hypocotyls
      transferred [(14)C]Gal from UDP-[(14)C]Gal into intact and partially hydrolyzed
      lupin beta-(1-->4)-galactans of various chain lengths as exogenous acceptors,
      while activity to endogenous acceptors was negligible. Maximal activity occurred
      at pH 6.5 and 20-25 degrees C in the presence of 25 mM Mn(2+) and 0.75% Triton X
      100. The transfer reaction onto the unmodified commercial pectic galactan (
      M(r)>150000) from lupin we used was very low but increased when the M(r) of the
      galactan was reduced by partial acid hydrolysis. Among the partially hydrolyzed
      galactans, high- M(r) (average M(r) 60000) beta-(1-->4)-galactan was a more
      efficient acceptor [specific activity 2000-3000 pmol min(-1) (mg protein)(-1)]
      than low- M(r) (average M(r) 10000 and 5000) polymers. Digestion of the
      radiolabeled product from high- M(r) galactan with endo-beta-(1-->4)-galactanase
      released mainly radioactive beta-(1-->4)-galactobiose and Gal, indicating that
      the transfer of [(14)C]Gal occurred through beta-(1-->4)-linkages. HPLC analysis
      showed that the enzyme also catalyzes incorporation of Gal into pyridylaminated
      (PA) beta-(1-->4)-galactooligomers with degree of polymerization at least 5.
      Gal(7)-PA chains were elongated by attachment of one, two, or three Gal residues
      leading to the formation of Gal(8-10)-PA.

PMID- 14661110
TI  - Postoperative functional outcome and stability in recurrent traumatic
      anteroinferior glenohumeral instability: comparison of two different surgical
      capsular reconstruction techniques.
AB  - INTRODUCTION: Patients (n=62) with recurrent traumatic anterior or anteroinferior
      glenohumeral instability were prospectively evaluated with reference to the
      surgical reconstruction technique performed. MATERIALS AND METHODS: Neer's T
      plasty procedure was performed in group I (n=31) while a modified, anatomically
      orientated, anteroinferior capsular shift was performed in group II (n=31). All
      patients underwent an additional Bankart repair. After 18.1 (group II) and 22.2
      (group I) months, patients were assessed in terms of subjective satisfaction,
      objective stability, range of motion, and functional outcome. RESULTS: No
      significant differences (91.5% group II, 87.8% group I) were noted between the
      study groups regarding the patient's subjective evaluation (p=0.17106). Results
      of Rowe's (93.1% group II, 87.9% group I; p=0.14419) and Constant's Score (96.5%
      group II, 93.8% group I; p=0.16582) showed no significant differences for both
      collectives. Postoperative lack of external rotation remained significantly
      smaller in group II (5.6 degrees +/-2.5 degrees ) compared with group I (9.8
      degrees +/-2.5; p=0.00028). Although no significant differences (p=0.612) were
      found, the rate of recurrence was obviously smaller in group II (group II vs
      group I: 6 patients). CONCLUSIONS: Our results demonstrate no significant
      differences between the two capsular reconstruction techniques regarding
      patient's satisfaction, Rowe and Constant Scores. However, the anatomically
      orientated anteroinferior capsular shift leads to a significantly smaller
      external rotation deficit and seems to offer a more reliable postoperative
      stability.

PMID- 14661109
TI  - Carboxypeptidase E in rat antropyloric mucosa: distribution in progenitor and
      mature endocrine cell types.
AB  - Processing of most gut hormones involves cleavage between dibasic amino acids
      followed by carboxypeptidase-catalyzed removal of the COOH-terminal basic
      residue, resulting in peptides with a COOH-terminal glycine. Such peptides may
      subsequently be converted to amidated peptides or can be directly secreted. It is
      believed that carboxypeptidase E (CPE) is involved in gut hormone processing but
      its presence in gut endocrine cells has never been studied. We have analyzed the
      distribution of CPE in the antropyloric mucosa of rat stomach and report that
      gastrin cells and progenitor gastrin-somatostatin (G/D) cells express CPE while
      mature somatostatin cells and the majority of serotonin cells fail to express
      CPE. These data indicate that immature G/D cells are able to process gastrin to
      glycine-extended forms and that CPE-mediated processing is not a characteristic
      of mature somatostatin and serotonin cells.

PMID- 14661112
TI  - The prevalence of symptomatic knee and distal interphalangeal joint
      osteoarthritis in the urban population of Antalya, Turkey.
AB  - The aim of this cross-sectional study was to estimate the prevalence and risk
      factors of symptomatic knee and distal interphalangeal (DIP) joint osteoarthritis
      (OA) in the elderly (> or =50 years of age) urban population of Antalya, Turkey.
      According to the 1997 national census, Antalya's population was 508,840. By
      random cluster sampling, 655 individuals aged 50 years or more were interviewed
      face-to-face and subjected to structured interviews regarding knee pain,
      worsening pain on exertion, and the gelling phenomenon. They were also asked
      about performing namaz (a fundamental act of worship in Islam performed five
      times a day), smoking, type of residence, type of toilet, work style, and
      duration of walking per day. They were also questioned about swelling in DIP
      joints. In the case of suspicion of knee OA, the individuals were invited to the
      hospital for further evaluation by physical examination and direct roentgenogram.
      The diagnosis of knee OA was based on clinical or clinical and radiographic
      findings. The prevalence of symptomatic knee OA was determined as 14.8% in the
      population aged 50 years or over. Advanced age, female sex, namaz, and type of
      residence were found to be associated with knee OA. The rate of symptomatic knee
      OA was significantly lower in smokers and those walking more than 2 h per day.
      Female sex was also strongly associated with OA DIP joints. OA of DIP joints was
      found significantly associated with symptomatic knee OA. The latter is a major
      health problem in the elderly population, especially in about one fourth of women
      aged 50 years or over. These data suggest that advanced age, female sex, and type
      of residence are risk factors.

PMID- 14661114
TI  - Successful treatment with micafungin of invasive pulmonary aspergillosis in acute
      myeloid leukemia, with renal failure due to amphotericin B therapy.
AB  - Invasive aspergillosis is an important factor in the morbidity and mortality of
      patients suffering from hematologic disorders treated with chemotherapy.
      Treatment with amphotericin B is often limited because of toxicity, particularly
      nephrotoxicity. We describe a case of invasive pulmonary Aspergillus fumigatus
      infection in acute myeloid leukemia with renal failure due to amphotericin B
      therapy, which responded to treatment with a new antifungal agent, micafungin.
      Micafungin appears to be an effective and safe therapy for Aspergillus infections
      with renal failure due to amphotericin B.

PMID- 14661113
TI  - Interleukin-1beta gene polymorphisms in Taiwanese patients with gout.
AB  - The purpose of this study was to examine whether interleukin-1 beta (IL-1beta)
      promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical
      manifestations in Taiwanese patients with gout. The study included 196 patients
      in addition to 103 unrelated healthy control subjects living in central Taiwan.
      From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta
      exon 5 were typed. Allelic frequencies were compared between the two groups, and
      the relationship between allelic frequencies and clinical manifestations of gout
      was evaluated. No significant differences were observed in the allelic
      frequencies of the IL-1beta promoter between patients with gout and healthy
      control subjects. Additionally, we did not detect any association of the IL-1beta
      promoter genotype with the clinical and laboratory profiles of gout patients.
      However, there was a significant difference between the two groups in terms of
      hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There
      was also a significant difference in the genotype of IL-1beta exon 5 polymorphism
      between patients with and without hypertriglyceridemia. Results of the present
      study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are
      not related to gout patients in central Taiwan.

PMID- 14661115
TI  - Global metabolic response of Escherichia coli to gnd or zwf gene-knockout, based
      on 13C-labeling experiments and the measurement of enzyme activities.
AB  - An integrated study on cell growth, enzyme activities and carbon flux
      redistribution was made to investigate how the central metabolism of Escherichia
      coli changes with the knockout of genes in the oxidative pentose phosphate
      pathway (PPP). Mutants deficient in glucose-6-phosphate dehydrogenase and 6
      phosphogluconate dehydrogenase were constructed by disrupting the zwf and gnd
      genes and were grown in minimal media with two different carbon sources, such as
      glucose or pyruvate. It was shown that the knockout of either gnd or zwf gene did
      not affect the cell growth rate significantly, but the cellular metabolism was
      changed. While the specific substrate uptake rate and the specific carbon dioxide
      evolution rate for either mutant grown on glucose were higher than those obtained
      for the parent strain, these two rates were markedly decreased in mutants grown
      on pyruvate. The measurement of enzyme activities implied a significant change in
      metabolism, when alternative pathways such as the Entner-Doudoroff pathway (EDP)
      and the malic enzyme pathway were activated in the gnd mutant grown on glucose.
      As compared with the parent strain, the activities of phosphoglucose isomerase
      were increased in mutants grown on glucose but decreased in mutants grown on
      pyruvate. The metabolic flux redistribution obtained based on 13C-labeling
      experiments further indicated that the direction of the flux through the non
      oxidative PPP was reversed in response to the gene knockout. Moreover, the
      knockout of genes caused an increased flux through the tricarboxlic acid cycle in
      mutants grown on glucose but caused a decrease in the case of using pyruvate.
      There was also a negative correlation between the fluxes through malic enzyme and
      isocitrate dehydrogenase in the mutants; and a positive correlation was found
      between the fluxes through malic enzyme and phosphoenolpyruvate carboxylase.

PMID- 14661116
TI  - Functional classification of the microbial feruloyl esterases.
AB  - Feruloyl esterases have potential uses over a broad range of applications in the
      agri-food industries. In recent years, the number of microbial feruloyl esterase
      activities reported has increased and, in parallel, even more related protein
      sequences may be discerned in the growing genome databases. Based on substrate
      utilisation data and supported by primary sequence identity, four sub-classes
      have been characterised and termed type-A, B, C and D. The proposed sub
      classification scheme is discussed in terms of the evolutionary relationships
      existing between carbohydrate esterases.

PMID- 14661117
TI  - Optimization of recombinant aminolevulinate synthase production in Escherichia
      coli using factorial design.
AB  - The production of recombinant Rhodobacter sphaeroides aminolevulinate (ALA)
      synthase was optimized in two strains of Escherichia coli: the wild-type strain
      MG1655, and a ptsG mutant AFP111. The effects of initial succinate, glucose and
      isopropyl-beta-d-thiogalactopyranoside (IPTG) concentrations and the time of
      induction on enzyme activity were studied. One-way analysis was used to
      approximate the optimal ranges for these factors, followed by a full factorial
      design to quantify the effects of each factor and the interactions between the
      factors. Initial succinate, glucose, and IPTG concentration were observed to be
      the key factors affecting ALA synthase activity with the optimal levels
      determined to be above 6 g/l succinate, 0 g/l glucose, and 0.10 mM IPTG. ALA
      synthase activity was generally lower with AFP111 than with MG1655, and the
      effect of these three key factors was also lower with AFP111 than with MG1655.
      Based on the full factorial design results, a fermentation was completed that
      yielded 296 mU/mg protein with a final ALA concentration of 5.2 g/l (39 mM).

PMID- 14661118
TI  - Distributing vertical forces between the digits during gripping and lifting: the
      effects of rotating the hand versus rotating the object.
AB  - During pinch grip we partition the vertical tangential forces at the digits
      according to the friction at the grip surfaces, and the mass distribution of the
      object. However, we cannot predictively partition the vertical forces to adjust
      to new frictional conditions after viewing a 180-deg rotation of an object with
      different textures at each grip surface. Hence, the processes that lead to
      predictive force partitioning may not access object representations, thereby
      suggesting that these processes are digit-specific. If this is true, then we
      should fail to predictively partition our fingertip forces when we rotate our
      hand. We tested this prediction by comparing the effects of object rotation with
      hand rotation for repeated lifts of an object that had one slippery grip surface
      and one rough grip surface. Subjects did not predictively redistribute the
      vertical tangential forces upon grasping the rotated object. Following object
      rotation, the vertical tangential force trajectories during the first 100 ms
      after contact indicated that 12/15 subjects failed to anticipate the reversed
      digit-friction relationships. All subjects appropriately partitioned the vertical
      tangential forces between the digits by the second lift after object rotation,
      confirming previous reports that sensory signals update the memory associated
      with lifting the object. In contrast, after hand rotation, 13/15 subjects
      anticipated the new digit-friction relationships and upon grasping the object
      immediately generated a steep rise in the vertical force trajectory at the rough
      surface. They also delayed the initial rise in vertical tangential force at the
      digit encountering the low-friction surface by approximately 65 ms. Thus,
      anticipatory partitioning of vertical fingertip forces is not strictly digit
      specific. Internally driven motor plans can access the relevant memories or
      internal models for predictively partitioning the vertical tangential forces. It
      is not clear if this process involves rotating internal representations of
      fingertip force directly, or if the forces are derived after internally rotating
      a representation of the object. In contrast to the robust effects of vision on
      reach kinematics, or on wrist and finger configuration, visual signals about
      object rotation and orientation apparently do not influence vertical tangential
      fingertip forces.

PMID- 14661119
TI  - When pros become cons for anti- versus prosaccades: factors with opposite or
      common effects on different saccade types.
AB  - In five experiments we compared prosaccade and antisaccade performance in normal
      human observers. This was first examined for visual stimulation in temporal or
      nasal hemifields, under monocular viewing. Prosaccades were faster following
      temporal than nasal stimulation, in accordance with previous results. The novel
      finding was that the opposite pattern was observed for antisaccades, consistent
      with a difficulty in overcoming a stronger prosaccade tendency after temporal
      hemifield stimulation. A second experiment showed that these results were not
      simply due to antisaccades following nasal stimulation benefitting from being
      made towards a temporal place-holder. Prosaccades and antisaccades were then
      compared for visual versus somatosensory stimulation. The substantial latency
      difference between prosaccades and antisaccades for visual stimuli was eliminated
      for somatosensory stimuli. Antisaccades can thus benefit in relative terms when
      the competing prosaccadic tendency is weakened; but two further experiments
      revealed that not all manipulations induce opposing outcomes for the two types of
      saccade. Although reducing the contrast of visual targets can slow prosaccades
      and conversely speed antisaccades, this was not the case at the lowest contrast
      level used, where both types of saccade were slowed, thus indicating some common
      limiting source. Moreover, warning sounds presented shortly before a visual
      target speeded both prosaccades and antisaccades. These results illustrate that
      several factors which slow prosaccades can speed antisaccades (consistent with
      competition between different pathways); but also reveal some notable exceptions,
      where both types of saccade are slowed or speeded together, suggesting some
      common pathways that may precede competition over the direction of the saccade.

PMID- 14661120
TI  - Postural muscle activity during bilateral and unilateral arm movements at
      different speeds.
AB  - The muscle activation patterns in anterior and posterior leg muscles were
      investigated with two types of perturbations to standing balance. Subjects stood
      with each foot on adjacent force platforms and performed arm flexion movements to
      shoulder height. Nine subjects performed ten repetitions unilaterally and
      bilaterally at 100, 75, 50, 25, and 12.5% of maximal acceleration as measured by
      an accelerometer placed on the dominant hand. Four subjects also performed the
      fastest movements while leaning forwards and backwards. The area and latency of
      the EMG activity from the quadriceps (QUAD), hamstrings (BF), soleus (SOL), and
      tibialis anterior (TA) were measured bilaterally, along with the excursions of
      the center of pressure (COP) during each movement. In both unilateral and
      bilateral tasks, subjects showed a scaling of EMG area and COP excursion with the
      acceleration of the arm movement. Prior to movement onset, significant scaling of
      EMG area with movement speed occurred in both unilateral and bilateral tasks in
      most muscles. Following movement onset, EMG areas scaled significantly to
      movement speed in only the anterior musculature, with the exception of the left
      BF. The latency of BF was consistent for the four fastest movements. Only the
      slowest movements resulted in a significant rightward shift of the BF EMG
      latency. During the unilateral task, the ipsilateral hamstrings were activated
      significantly earlier than in the bilateral task and the contralateral hamstrings
      were activated significantly later. It was also observed that subjects utilized
      one of two different strategies to maintain balance. Five individuals displayed
      simultaneous anterior/posterior muscle activation while the other four displayed
      a reciprocal pattern of activation. Regardless of the initial standing position
      (leaning forwards or backwards), subjects used the same simultaneous or
      reciprocal activation strategy. The results indicate that muscle activation
      patterns change with different tasks, but remain the same during variations of
      the same task.

PMID- 14661121
TI  - [Changes in trends and fashions in the upper gastrointestinal tract: focus on the
      esophagus].

PMID- 14661122
TI  - Impact of reflux disease on general and disease-related quality of life -
      evidence from a recent comparative methodological study in Germany.
AB  - BACKGROUND: The clinical and socioeconomic burden of gastro-esophageal reflux
      disease (GERD) is considerable. The primary symptom of GERD is heartburn, but it
      may also be associated with extraesophageal manifestations, such as asthma, chest
      pain and otolaryngologic disorders. AIM: To describe the impact of heartburn on
      patients' Health-Related Quality of Life (HRQL) in Germany, using validated
      generic and disease-specific instruments to measure patient-reported outcomes.
      METHOD: Patients with symptoms of heartburn completed the German versions of the
      Gastrointestinal Symptom Rating Scale (GSRS), the Quality of Life in Reflux and
      Dyspepsia questionnaire (QOLRAD), the Short Form-36 (SF-36) and the Hospital
      Anxiety and Depression (HAD) scale. Frequency and severity of heartburn during
      the previous 7 days were also recorded. RESULTS: 142 consecutive patients
      completed the assessments (mean age of 47.5 years, SD = 14.6; 55.6 % female). 70
      % of patients had moderate symptoms. Over half (68 %) had symptoms on more than 4
      days in the previous week. Patients were most bothered by symptoms of reflux with
      a mean GSRS score, (ranges from 1 [not bothered] to 7 [very bothered]), of 3.9,
      indigestion of 3.3 and abdominal pain of 3.0, respectively. As a result of their
      symptoms, patients experienced problems with food and drink. The mean QOLRAD
      score (ranges from 1 to 7; the lower the value the more severe the impact on
      quality of life) of daily functioning was 4.4, impaired vitality 4.6, emotional
      distress 5.0 and sleep disturbance 5.1, respectively. This led to impaired
      overall HRQL across all domains (mean SF-36 score of this heartburn population
      compared to a general population in Germany). Using HAD, 25 % of patients were
      anxious and 8 % were depressed. CONCLUSION: There is consistent evidence that
      heartburn substantially impairs all aspects of health-related quality of life.

PMID- 14661123
TI  - [Osteoporosis in inflammatory bowel disease - results of a survey among members
      of the German Crohn's and Ulcerative Colitis Association].
AB  - INTRODUCTION: Osteoporosis is a frequent and clinically important complication in
      inflammatory bowel disease (IBD). Prevalence and risk factors have been examined
      in small numbers of patients. With a nationwide survey of members of the German
      Crohn's and Ulcerative Colitis Association (DCCV) we wanted to evaluate the
      situation in a larger group of patients. METHODS: Questionnaires were sent with
      the autumn issue of the members journal to approx. 14,620 affected members of the
      DCCV. Items covered osteoporosis, clinical symptoms, anamnesis and
      sociodemographic topics. Results are presented as descriptive analysis and in a
      logistic regression analysis of factors contributing to the osteoporosis risk.
      RESULTS: 2,536 questionnaires could be used (17.3 %). Mean age and distribution
      concerning diagnosis and gender were comparable to the DCCV members in total. The
      prevalence of pathologic bone density was 62.3 % in those 1,265 patients (50.1 %)
      who underwent bone densitometry in the course of their disease. The analysis led
      to the following possible risk factors: disease activity (high chronic activity
      or more than 1 acute flare annually vs. remission, p < 0.001), lifetime steroid
      dosage > 10 g (p = 0.002), Crohn's disease vs. ulcerative colitis (p = 0.02),
      multiple bowel resection (p = 0.032), age (p = 0.018) and low body mass index (p
      = 0.034). 83.4 % of the patients with pathologic bone density received specific
      therapy, but most of those (63.5 %) were solely substituted with calcium and
      vitamin D. CONCLUSION: This is the first study looking at epidemiology and risk
      factors of osteoporosis in a large study population of patients with inflammatory
      bowel disease. Although the prevalence may be overestimated due to selection bias
      in our study, osteoporosis is confirmed as a frequent and clinically relevant
      complication in IBD. Bone densitometry is recommended in those patients with one
      or more risk factors.

PMID- 14661124
TI  - [Endoscopic ultrasound in the long-term follow-up of primary lymphomas of the
      stomach under conservative therapy].
AB  - BACKGROUND AND AIMS: The stomach is the main site of primary extranodular
      manifestation of non-Hodgkin's lymphomas. Besides clinical staging additional to
      histological diagnoses, the endoscopic ultrasound (EUS) also becomes more
      important during follow-up courses of conservative therapy regimens (e. g. H.p.
      eradication; radiochemotherapy). The aim of the present study was to assess the
      impact of EUS during long-term observation of primary gastric lymphomas and to
      outline possible changes of the gastric wall. PATIENTS AND METHODS: Within the
      scope of 2 prospective multicenter study on primary gastrointestinal non
      Hodgkin's lymphomas (GIT-NHL), which were performed at Muenster University
      Hospital, 26 patients undergoing conservative treatment were examined with
      endoscopic ultrasound at a three-month interval between 01/1992 and 11/1998. The
      mean survey period was 28 months (range 7-62). RESULTS: In 22 patients over a
      period of 21 months (range 4-51) a histological proven complete remission (CR)
      was found. In 2 patients only a partial remission (PR) was achieved within a time
      period of seven respectively eight months of survey. Two other patients developed
      early relapse of non-Hodgkin's lymphoma. In patients with CR the endoscopic
      ultrasound showed a highly significant decrease of gastric wall thickness 7 and
      12 months after therapy was started. On average after 4.6 months enlarged lymph
      nodes were no more detectable, after 5.5 months thickness of the gastric wall and
      finally after 6.6 month the previous abolished layering of the gastric wall
      returned to normal. CONCLUSION: In patients with gastric non-Hodgkin's lymphomas
      endoscopic ultrasound seems to be the only valid method which demonstrates early
      changes of the gastric wall and its layering in an appropriate way and might
      therefore in addition be capable to differentiate between CR, recurrent or
      refractory non-Hodgkin's lymphoma.

PMID- 14661125
TI  - Dramatic increase in bilirubin after ERCP - pethidine as a possible cause of drug
      induced hepatitis.
AB  - We report on a 68-year-old female patient who was admitted with abdominal pain.
      Elevated lipase and CRP caused us to suspect pancreatitis. Because an enlarged
      pancreas head was found on ultrasound, an endoscopic retrograde cholangio- and
      pancreaticography was performed with a pethidine-containing premedication.
      Thereafter, bilirubin, gamma-glutamyl transpeptidase and alkaline phosphatase
      increased dramatically. There was also a moderate elevation of aspartate
      aminotransferase and alanine aminotransferase. A second endoscopic retrograde
      cholangio- and pancreaticography with the same premedication was performed in
      order to exclude an undetected concretion. This led to a further increase of
      bilirubin. An association with the drugs given as premedication was therefore
      suspected, and in fact, a hypersensitivity reaction towards pethidine was
      confirmed by the lymphocyte transformation test. We thus conclude that pethidine
      caused an immunologically mediated hepatic injury.

PMID- 14661126
TI  - [Mirizzi Syndrome without Cholecystolithiasis].
AB  - BACKGROUND: Mirizzi syndrome is a rare cause of biliary symptoms and jaundice. It
      describes an obstruction of the common hepatic bile duct by external compression
      caused by an impacted gallstone in the gallbladder neck or cystic duct. This
      setting is usually associated with cholecystolithiasis. CASE REPORT: A 64-year
      old caucasian woman with intermittent abdominal pain and newly diagnosed jaundice
      was admitted to our clinic. An ERC was performed a few weeks earlier because of
      similar complaints without jaundice. At that time there was no evidence of
      choledocholithiasis. Now ERC surprisingly showed a gallstone impacted in the
      cystic duct, leading to an external compression of the common hepatic bile duct
      (Mirizzi syndrome). Since an endoscopic stone extraction failed, surgical
      intervention was performed. A laparoscopic cholecystectomy was performed without
      trans-cystic stone removal. After removal of the bile duct drainage it became
      evident that the impacted stone was still located in the remaining part of the
      cystic duct. After successful endoscopic extraction of the impacted stone the
      patient remained free of symptoms without recurrent jaundice. CONCLUSION: In rare
      cases Mirizzi syndrome without cholecystolithiasis can cause biliary symptoms. A
      close interdisciplinary cooperation is necessary in order to guarantee an
      excellent therapeutic management.

PMID- 14661127
TI  - [Improved detection and characterisation of liver tumors with echo-enhanced
      ultrasound].
AB  - Contrast-enhanced ultrasound techniques represent the most challenging efforts in
      recent ultrasound developments. Contrast-enhanced imaging of the liver will be
      reviewed with respect to the literature and our own experience. Echo-enhancing
      agents, also known as ultrasound contrast media, have improved the accuracy of
      liver ultrasound within recent years. The characterisation of focal liver lesions
      which is possible by flow characteristics and the improved detection of liver
      tumors give special importance to the contrast agents. The agents consist of air
      or gas bubbles coated with different shell media. These micro-bubbles act as
      strong reflectors to the ultrasound beam enhancing the backscatter signal up to
      30 dB. There are differences between blood pool agents and agents with a liver
      specific late phase. The agents remain in the vessels during the vascular phase
      and lead to enhancement of different structures (arterial, capillary, portal
      venous, and sinusoidal perfusion). This is the first real-time imaging technique
      of liver lesions that allows a unique analysis of tumor perfusion. Liver tumors
      known to be hyperperfused in the arterial phase (e. g., focal nodular
      hyperplasia, hepatocellular carcinoma, and hyperperfused metastases) can be
      detected and characterised. Hypoperfused tumours (e. g., liver metastases of the
      gastrointestinal tract) can be recognised in the portal venous phase as less
      perfused "black spots". Due to of the recently available improved ultrasound
      technology and affordable ultrasound systems, a reduction in the use of computed
      tomography (CT) and magnetic resonance imaging (MRI) may be possible, allowing
      these important technologies to be available for other indications (e. g., brain,
      thorax).

PMID- 14661132
TI  - [Methods of process management in radiology].
AB  - The main emphasis in health care has been on quality and availability but
      increasing cost pressure has made cost efficiency ever more relevant for nurses,
      technicians, and physicians. Within a hospital, the radiologist considerably
      influences the patient's length of stay through the availability of service and
      diagnostic information. Therefore, coordinating and timing radiologic
      examinations become increasingly more important. Physicians are not taught
      organizational management during their medical education and residency training,
      and the necessary expertise in economics is generally acquired through the
      literature or specialized courses. Beyond the medical service, the physicians are
      increasingly required to optimize their work flow according to economic factors.
      This review introduces various tools for process management and its application
      in radiology. By means of simple paper-based methods, the work flow of most
      processes can be analyzed. For more complex work flow, it is suggested to choose
      a method that allows for an exact qualitative and quantitative prediction of the
      effect of variations. This review introduces network planning technique and
      process simulation.

PMID- 14661133
TI  - A new concept for covered stent protected carotid angioplasty: an ex vivo study.
AB  - OBJECTIVE: To determine the efficacy of a covered stent prototype designed for
      protected carotid angioplasty to reduce cerebral embolization. MATERIAL AND
      METHOD: The covered stent tested is made of nitinol, coated with a polyurethane
      membrane (MembraX trade mark; porous size 80 micro m). In a bench-top model (flow
      rate 650 ml/min, pulsatile flow [dicrote] 123 Pulses/min, pressure 100/60 mm Hg
      [mean pressure 80 mmHg]) with inserted human carotid (n = 6) stent implantation
      was performed (8/32 mm). Passed particles (mg) were determined in the effluent of
      a 100 micro m filter prior to intervention, after stent deployment and after
      final dilation (5 mm). RESULTS: When stenting carotid arteries obtained from
      human cadavers, the highest rate of particle embolization was measured while
      crossing the lesion with the delivery device (6,8 mg; for all p < 0,05),
      embolization after additional balloon angioplasty and particle rates measured in
      the effluent filter prior covered stent placement were significantly lower (3,8
      mg; p < 0,05). Branches of the external carotid artery remained patent in all
      cases. CONCLUSIONS: The introduced concept of covered stent protected carotid
      angioplasty with the MembraX trade mark prototype has proven promising results
      for low cerebral embolization rates ex vivo. Further evaluations using an animal
      model and a miniaturization of the delivery device are warranted prior to human
      use.

PMID- 14661134
TI  - [The role of MRI in suspected inner ear malformations].
AB  - PURPOSE: This is a prospective analysis of the value of MRI in suspected inner
      ear malformations. MATERIALS AND METHODS: In 50 patients (43 children and young
      adults, 7 adults) with suspected inner ear malformation MRI (1.5 T) was
      performed. In addition, 42 of these patients underwent CT. For the analysis of
      the inner ear structures, the constructive interference in steady state (CISS)
      sequence with 0.7 mm slice thickness was used. Functional tests revealed a
      sensorineural hearing loss or deafness in 82 temporal bones (TB) and a combined
      hearing loss in 4 TB. The hearing loss was unilateral in 14 patients. MRI and CT
      findings were compared. RESULTS: Imaging findings were normal in 58 TB. The
      pathological findings included inner ear malformations (35 TB), inflammatory
      changes (4 TB), partial obliteration of labyrinth (2 TB) and congenital aural
      atresia (1 TB). An isolated absence of the cochlear nerve (1 TB) could only be
      found by MRI. In the remaining cases, an inner ear malformation was diagnosed by
      MRI and CT with the same confidence but MRI was superior in displaying the fine
      details. CONCLUSIONS: MRI will become the method of choice in the diagnosis of
      inner ear malformations.

PMID- 14661135
TI  - [Pre- and postoperative assessment of hemodynamics in patients with chronic
      thromboembolic pulmonary hypertension by MR techniques].
AB  - PURPOSE: To evaluate the potential of MRI to grade cardiac impairment and
      pulmonary hypertension in patients with chronic thromboembolic pulmonary
      hypertension (CTEPH) in comparison with invasive pressure measurements before and
      after surgery. MATERIALS AND METHODS: We examined 35 patients with CTEPH before
      and after pulmonary thromboendarterectomy (PTE). For assessment of hemodynamics,
      velocity-encoded segmented GE-sequences (pulmonary arteries and ascending aorta)
      and segmented cine GE-sequences along the short axis of the heart were performed.
      The analysis comprised calculation of ejection fractions, peak velocities, mean
      pulmonary arterial flow and vessel diameter. 10 volunteers served as controls.
      Flow measurements were compared to invasively measured mean pulmonary arterial
      pressure (MPAP) and vascular resistance (PVR). RESULTS: Compared to volunteers,
      CTEPH-patients showed significantly reduced right ventricular ejection fractions
      (p < 0.001), pulmonary peak velocity (p < 0.001) and significantly increased
      diameters of the pulmonary arteries (p < 0.001). The flow measurements in the
      aorta (2713 ml/min) and the pulmonary arteries (2088 ml/min) revealed a large
      bronchopulmonary shunt. After PTE, there was a significant reduction in vessel
      diameter (p < 0.001). This was associated with a significant increase in
      pulmonary peak velocities (p < 0.001). The increase in pulmonary peak velocities
      correlated with the decrease of PVR (r = 0.5) and MPAP (r = 0.6). The ejection
      fraction of the right ventricle correlated with PVR (r = 0.6) and MPAP (r = 0.7).
      The postoperative decrease in MPAP correlated with the increase in right
      ventricular ejection fraction (r = 0.8). After PTE there was no bronchopulmonary
      shunt volume. All patients had an inverse motion of the interventricular septum.
      It returned to normal in 68 % of patients after surgery. CONCLUSION: Breath-hold
      MR-techniques enable non-invasive assessment of pulmonary hemodynamics in
      patients with CTEPH. For postoperative follow-up studies MRI could be considered
      the modality of choice.

PMID- 14661136
TI  - [Automatic classification of liver segments according to Couinaud: development of
      a new algorithm and evaluation spiral CT data].
AB  - PURPOSE: To develop a software tool that analyzes the anatomy of the portal vein
      branches and assigns segmental and subsegmental branches according to Couinaud's
      classification system and to evaluate its accuracy. MATERIALS AND METHODS: The
      algorithm was developed in C++ on a PC. The algorithm recognizes the three major
      branching patterns of the portal vein. Segmental and subsegmental branches are
      assigned to 8 segments following Couinaud and encoded by 8 colors. The software
      was evaluated using CT data sets of 39 patients. After the individual segmental
      anatomy of each patient was determined by an experienced radiologist, automatic
      classification was performed and the results were compared on a branch by branch
      basis. RESULTS: The numbering was accurate according to Couinaud's system in 358
      of 409 segmental and subsegmental branches (88 %). The assignment failed in 51 of
      409 branches due to unexpected anatomy or software problems. CONCLUSION:
      Automatic classification of portal vein branches and their appendant parenchyma
      is possible. The automatic designation of liver segments enables the three
      dimensional visualization of the segmental anatomy. In the future, automatic
      analysis might facilitate the reporting and communication of CT findings.

PMID- 14661137
TI  - [MRI staging of prostate cancer with the combined endorectal body phased-array
      coil and histologic correlation].
AB  - PURPOSE: Evaluation of the diagnostic value of the combined endorectal body
      phased array technique regarding the staging of prostate cancers, especially in
      the differentiation between stages T2 and T3. MATERIALS AND METHODS: Forty-two
      patients with biopsy-proven or clinically suspected prostate cancer were examined
      on a 1.5 T scanner (Siemens, Symphony) prior to radical prostatectomy. T (2)
      weighted TSE (axial, coronal) and T (2)-weighted FSE (axial) sequences were
      obtained with and without fat suppression. After application of 0.2 mmol/kg body
      weight Gd-DTPA, T (1)-weighted GRE sequences were obtained using dynamic MRI. All
      images were prospectively interpreted by two observers. The MR images were
      correlated with the histopathological findings of wide-area sections of
      prostatectomy specimens. RESULTS: For the detection of extracapsular growth and
      seminal vesicle infiltration (T2 versus T3) the accuracy was between 94 % and 97
      % (sensitivity 100 %, specificity between 87 % and 93 %, observer 1 and 2). In
      two cases with a histologically proven stadium pT2b, observer 1 had diagnosed
      stadium pT3a. The results of observer 2 were marginally better in only one case,
      which was histologically proven to be pT2b and overstaged as pT3a. MRI did not
      lead to under-staging of a single tumor with regard to the differentiation
      between T2 and T3. Overall, the staging of the tumor stages (T1 - T4) was correct
      in 25 of 33 cases (75 %). The dynamic MRI showed no improvement regarding
      sensitivity (100 %) and specificity (62 %) and achieved a staging accuracy of
      only 75 %. CONCLUSION: MRI performed with a combination of a pelvic phased-array
      coil (PPA) and integrated endorectal coil plays a significant role in the
      preoperative staging of prostate cancer. However, differentiation between
      capsular infiltration (T2) and penetration (T3) as well as evaluation of the
      seminal bladder (T3b) seem to be difficult.

PMID- 14661138
TI  - [CT in ureterolithiasis with a radiation dose equal to intravenous urography:
      results in 209 patients].
AB  - PURPOSE: To evaluate a low-dose, nonenhanced helical CT protocol for the
      diagnosis of renal colic using an effective dose equivalent of radiation not
      higher than that of intravenous urography. MATERIALS AND METHODS: A new low-dose
      helical-CT protocol (120 kV; 70 mA; rotation time 0.75 s; collimation 5 mm, pitch
      = 2) was used to examine 209 consecutive patients with symptoms of renal colic.
      The initial CT reports were compared with retrograde ureterography, ureteral
      endoscopy, stone retrieval, surgical or clinical findings. The effective
      radiation dose was calculated by the method published by Nagel. The prevalence of
      ureterolithiasis was 70 %. RESULTS: Sensitivity and specificity of the low-dose
      helical CT in detecting ureteral calculi were 97.7 % and 96.8 %, respectively.
      The positive predictive value was 99.3 % and negative predictive value 92.4 %.
      The mean effective radiation dose equivalent was 0.97 mSv in male and 1.35 mSv in
      female patients. CONCLUSIONS: The diagnostic value of the reported CT protocol
      does no differ from previously published protocols. However, the effective
      radiation dose equivalent is at least 50 % lower than stated in the published
      protocols. We recommend the low-dose helical CT protocol as the method of choice.

PMID- 14661139
TI  - [MRI-guided pediatric interventions].
AB  - AIM: There are only a few diagnostic or therapeutic procedures where MR imaging
      is applied during pediatric interventions. This study will describe indications,
      complications as well as the advantages and disadvantages of MRI-guided
      interventions based on a case study in an open MRI scanner. MATERIALS AND
      METHODS: 14 procedures were performed in an open MRI scanner (Signa SP/i, GEMS)
      on 13 children (1 - 16 yr) with bone, soft tissue and brain lesions (1 - 4 cm
      diameter). Localization of the pathology, targeting and final control of the
      result were based on images acquired with SE-, 3D-, GE-sequences pre- and post
      contrast as well as FSE-sequences. Interactive MRI-guided instrument navigation
      was performed using a multiplanar T1w GE-sequence. RESULTS: Eight biopsies (incl.
      1 rebiopsy), two tumor resections, one removal of a free joint mouse and three
      tumor-markings were performed without complications. Five biopsies provided
      appropriate sample quality for a histological diagnosis while two samples were
      too fragmented requiring a second biopsy (one of them MRI-guided). Surgical
      progress during tumor resection and marking could be controlled during the
      intervention without repositioning the patient. DISCUSSION: MR image guided
      pediatric interventions combine the advantage of an imaging system without
      ionizing radiation and the high soft-tissue contrast. The low number of these
      kinds of procedures can be explained by the relatively high costs for the
      intervention, the increased duration for each procedure and the limited
      availability of open MRI systems. The integrated localization-system helps during
      planning of the access path when facing complex anatomical structures and
      provides safe navigation in sensitive regions like the epiphyseal cartilage.
      Recent and expected developments of the required MR-compatible biopsy instruments
      could provide higher efficiency for appropriate sample size and quality.
      Summarizing, MRI-guided pediatric interventions have shown to be a promising
      method at the beginning of its development.

PMID- 14661140
TI  - [Influence of endoleaks on aneurysm volume and hemodynamics after endovascular
      aneurysm repair].
AB  - PURPOSE: To evaluate the aneurysm volume and the intra-aneurysmatic pressure and
      maximal pressure pulse (dp/dtmax) in completely excluded aneurysms and cases with
      endoleaks. MATERIALS AND METHODS: In 36 mongrel dogs, experimental autologous
      aneurysms were treated with stent-grafts. All aortic side branches were ligated
      in 18 cases (group I) but were preserved in group II (n = 18). Aneurysm volumes
      were calculated from CT scans before and after intervention, and from follow-up
      CT scans at 1 week, 6 weeks and 6 months. Finally, for hemodynamic measurements,
      manometer-tipped catheters were introduced into the excluded aneurysm sac (group
      I and II), selectively in endoleaks (group II), and intraluminally for aortic
      reference measurement. Systemic hypertension was induced by volume load and
      pharmacologic stress. Pressure curves and dp/dt were simultaneously recorded and
      the ratios of aneurysm pressure to systemic reference pressure calculated.
      RESULTS: At follow-up, type-II. endoleaks were excluded in all cases of group I
      by selective angiography. In contrast, endoleaks were evident in all cases of
      group II. Volumetric analysis of the aneurysms showed a benefit for group I with
      an improved aneurysm shrinkage: DeltaVolume + 0.08 %, - 1.62 % and -9.76 % at 1
      week, 6 weeks and 6 months follow-up (median, group I), compared to + 1.43 %, +
      0.67 %, and - 4.04 % (group II), p < 0.05. In case of complete aneurysm exclusion
      the ratio of systolic aneurysm pressure to systemic reference pressure was 0.662,
      0.575 and 0.385 (median) at 1 week, 6 weeks and 6 months. The corresponding
      dp/dtmax ratios were 0.12, 0.07 and 0.04, respectively. However, within endoleaks
      selective measurements showed significantly increased pressure load: the ratios
      of systolic endoleak pressure to systemic reference pressure and the
      corresponding ratios for dp/dtmax were 0.882 and 0.913 (median), respectively.
      These hemodynamic findings were linear from hypotension, physiologic blood
      pressure to hypertension. CONCLUSION: Occlusion of all aortic side branches of an
      aneurysm prior to stent-grafting reduces endoleaks and promotes aneurysm
      shrinkage. Complete aneurysm exclusion significantly reduces systolic pressure
      and dp/dt max. In contrast, endoleaks showed nearly systemic pressure load and
      undamped pulsatility.

PMID- 14661141
TI  - [Preliminary experience with balloon kyphoplasty for the treatment of painful
      osteoporotic compression fractures].
AB  - PURPOSE: To describe the technique and to evaluate the safety and efficacy of
      percutaneous kyphoplasty as a new treatment in patients with painful osteoporotic
      vertebral body compression fractures of the lumbar and thoracic spine. MATERIALS
      AND METHODS: In this prospective study balloon kyphoplasty was performed in 34
      consecutive patients (25 females, 9 males; mean age 75 years) with 56 painful
      osteoporotic vertebral fractures (from T6-L5), of which 22 showed a posterior
      wall involvement and retropulsion on preoperative CT. The median duration of
      symptoms was 9.7 weeks. Symptomatic levels were identified by correlating the
      clinical presentation with MRI, conventional radiographs and CT including bone
      densitometry. Pre- and postoperative examinations (radiographs, CT) as well as
      Karnofsky and visual analogy pain scores (Visual Analog Scale = VAS) were
      documented and compared to evaluate the success of the procedure. RESULTS: The
      median Karnofsky score improved from 40 % (pre-) to 70 % (post-treatment).
      Simultaneously, median pain scores (VAS) decreased from 64 (pre-) to 21 (post
      treatment) (p < 0.001). Perioperative morbidity included one transient L2 nerve
      root bruise. The procedure led to a partial restoration of the height of the
      vertebral body by reducing the median sagittal index from 11.5(3) to 5(3). In
      none of our patients, the procedure led to worsening of the fracture-induced
      narrowing of the spinal canal. Clinically asymptomatic cement leakage occurred in
      10 cases, with leakage 4 times into the paraspinal space, 3 times into the spinal
      canal and 3 times into the disc space. CONCLUSION: Balloon kyphoplasty is a safe
      and effective procedure. It is applicable even in fractures with posterior wall
      involvement since it is a low-pressure technique in contrast to vertebroplasty
      and restores vertebral body height partially. It results in immediate clinical
      improvement of mobility and pain relief. While short-term results are excellent,
      follow-up data have to be awaited for the final judgment of this method.

PMID- 14661142
TI  - [Prospective cost-benefit analysis of a fully digitized working environment in an
      ultrasound division applying process simulation].
AB  - PURPOSE: Quantification of expected savings of work load and personnel costs
      after implementation of a digital infrastructure in an ultrasound division of a
      radiology department. MATERIALS AND METHODS: The work flow of an ultrasound
      examination was simulated by means of a computer model. After validation, the
      computer model was modified to represent a work flow with PACS, electronic
      patient record, and automatic scheduling. The simulation results of work load,
      equipment utilization, and personnel costs were compared for both scenarios.
      RESULTS: The total number of work steps was reduced from 29 in the conventional
      scenario to 14 work steps in the scenario with digital infrastructure. The work
      load of administrative activities decreased by 89 % whereas the work load of
      activities directly related to the ultrasound examination remained unchanged. The
      productive personnel costs declined from euro; 24 to euro; 16 per examination.
      The gross labor costs declined from euro; 33 to euro; 20 per examination. Given
      unchanged equipment and number of patients, the required number of physicians can
      be reduced from 3 to 2 and that of technicians from 2 to 1 by use of a digital
      infrastructure. CONCLUSION: A digital infrastructure possesses a great potential
      for efficiency provided that it is implemented comprehensively and the work flow
      is adapted utilizing the capabilities of automation in all work processes.

PMID- 14661143
TI  - Predialing the number of cinegraphic frames enables an effective patient dose due
      to coronary angiography of 0.8 mSv.
AB  - PURPOSE: To investigate the effect of a new device for predialing the number of
      cinegraphic frames before each coronary angiogaphy, with the objective of
      reducing the patient dose area product (DAP) from coronary angiography, which
      typically requires 1000 to 2350 cinegraphic frames. That DAP is high and stated
      to be between 15.6 to 106.3 Gy x cm (2). Applying the accepted DAP-to-ED
      conversion factors, for the thoracic region of approximately 0.20 mSv/Gy x cm
      (2), this corresponds to a mean effective dose (ED) in the range of 3.1 to 21.3
      mSv. MATERIAL AND METHODS: For patients undergoing elective coronary angiography,
      we compared various parameters of radiation exposure obtained with judicious
      radiation reducing standard techniques (n = 106) and with an additional new
      rotary switch for predialing the number of cinegraphic frames (n = 106). RESULTS:
      The patient radiation dose was significantly lower with the new device, with the
      mean DAP reduced to 5.5 from 9.1 Gy x cm (2). The corresponding reducation of the
      mean DAP for left ventriculography and coronary angiography was 1.3 from 1.7, and
      4.2 from 7.4 Gy x cm (2), respectively. The number of cinegraphic frames was 98
      vs. 184, whereas the number of cinegraphic runs and the fluoroscopy time were
      comparable. CONCLUSION: Predialing the cinegraphic frame number before each
      cinegraphic run enables a reduction of the patients effective dose from coronary
      angiography to 0.8 mSv, i. e. to 57 % of the baseline value and far below
      typically reported values.

PMID- 14661144
TI  - [Systematics of imaging artifacts in MRT caused by metallic vascular implants
      (stents)].
AB  - PURPOSE: Imaging artifacts in magnetic resonance tomography (MRT) caused by
      metallic vascular implants (stents) were characterized systematically in
      dependence on the material and the construction of the implants as well as with
      respect to different measurement protocols and for different static field
      strength B (0). METHODS: Twelve stents, different in material (stainless steel,
      nitinol, Co-alloy) and/or construction, were examined at B (0) = 0.2 T and 1.0 T
      with two 2D gradient echo (GE) sequences (TE = 4 and 10 ms), one 3D GE sequence
      and one spin echo (SE) sequence. The stents were put into water with Gd-DTPA
      contrast agent. The dependence on the orientation was analyzed for the 9
      possibilities of an orthogonal alignment of the stent axis, the direction of B
      (0), the slice, the read out, and the phase encoding direction. Special interest
      was given to the visibility of the stent lumen at forced rf excitation, as well
      as to the influence of broken struts on the signal obtained. RESULTS: For the
      examined stents GE technique showed, due to spin dephasing regions a total signal
      loss ranging up to 8 mm away from the stent mashes. The value depends on the
      stent material, the stent orientation in the scanner and grows with voxel size,
      echo time and B (0). In SE technique dephasing artifacts vanish and wrong spatial
      encoding gets visible, rf shielding is more pronounced. The visibility of the
      stent lumen ranges from nearly unperturbed down to a complete signal loss. An
      improvement is possible using enlarged flip angles. Broken struts can not be
      imaged significantly. DISCUSSION: The MR representation of metallic stents
      commercially available at the time, especially of nitionol stents, can be
      optimized with a suitable adaptation of the imaging parameters. However, a
      profound improvement can only be expected from new stent material and design.

PMID- 14661146
TI  - [Spatial resolution of digital systems: is the visual determination with a lead
      bar pattern meaningful?].
AB  - The factors influencing the spatial resolution of digital detectors are discussed
      and demonstrated on simulated bar pattern images. Lead bar patterns are often
      used in quality control procedures to test the spatial resolution of image
      detectors. In digital imaging systems the pixelization of the detector interferes
      with the periodic bar pattern and makes it difficult to determine the resolution
      limit. Bar pattern images seem to have only limited value for characterizing the
      imaging performance of digital detector systems.

PMID- 14661145
TI  - [Flexible applicator systems for radiofrequency ablation (RFA) of hepatic
      tumors].
AB  - PURPOSE: To report our experience with flexible applicators in radiofrequency
      ablation (RFA) of hepatic tumors. MATERIALS AND METHODS: In 6 liver tumors in 6
      patients, a flexible RFA-applicator system (RITA StarBurst FLEX, RITA Medical
      Systems, Mountain View, CA, USA) was placed under CT guidance. The Seldinger
      technique with an 11G access system (RITA StarBurst Access) was used to place the
      application system into the liver. Before and within a week after the ablation,
      all tumors were investigated with contrast-enhanced MRI. RESULTS: The Seldinger
      technique accommodated the placement of a thin 17.5-gauge needle for the initial
      puncture, enabling easy adjustment of the position of the needle. The flexible
      applicator of the RFA system could be placed in 4.5 (+/- 1.8) minutes on average.
      CONCLUSION: Flexible applicators facilitate CT-guided RFA and can be placed using
      the Seldinger technique.

PMID- 14661147
TI  - [Successful therapy of post-traumatic aneurysma spurium by ultrasound-guided
      percutaneous thrombin injection].

PMID- 14661148
TI  - MR appearance of uterine cervical small cell carcinoma.

PMID- 14661149
TI  - [Focal concentrations in the hepatic CT in superior vena cava thrombosis].

PMID- 14661150
TI  - [Deep impact--consequences for young scientists and money distribution].

PMID- 14661151
TI  - [Measures of grief--a critical review].
AB  - Scientific investigations show that the course of a grieving process may have a
      substantial impact on the mental and physical wellbeing of those concerned. An
      international survey of measuring instruments designed to register grief shows
      little conformity with respect to the key symptoms of grieving. Only few
      instruments are derived from scientific theory, the majority have been developed
      on the basis of clinical observations and only some of the instruments are
      psychometrically designed. Some instruments display correlations with other
      constructs such as depression and anxiety, with the question of whether the
      symptoms are grief-specific or autonomous remaining unanswered. Only few
      instruments serve to differentiate between normal and pathologic grief. The fact
      that only two German-language instruments for registering grief are available to
      date also indicates that this subject matter has attracted only scant attention
      despite its clinical significance. In conclusion, the demands to be made on an
      instrument to be developed in the future are outlined.

PMID- 14661152
TI  - [Psychosomatic complaints and utilisation of psychosomatic consultation services
      in gynecology and obstetrics].
AB  - The aim of this study was to identify symptoms of depression, anxiety and
      somatization disorder in gynecological and obstetrical inpatients by screening
      questionnaires and to compare this findings with utilisation of a psychosomatic
      consultation service. 517 patients were screened with HADS (anxiety and
      depression) and GBB-24 (somatic complaints). 28.7% had pathological and, in
      addition, 19.8% borderline scores in at least one scale. More than 40% had
      pathological or borderline scores even in a 4-week follow-up and emphasised that
      they would have preferred having psychosomatic support in hospital. In only 2.9%
      psychosomatic consultation service was requested. Physicians in the gynecology
      department rated anxiety depression and the patients' acceptance of psychological
      factors of their illness significantly lower than the patients themselves. Our
      results demonstrate that anxiety and depression in gynecological and obstetric
      patients are not only a momentary phenomenon. Physicians underestimate the need
      of psychosomatic consultation.

PMID- 14661153
TI  - [Medical psychology in Germany--a discipline between continuity and change].
AB  - In 2002 a survey of institutes of Medical Psychology was accomplished in order to
      describe the situation of the subject. As regards the content the survey referred
      to five scopes: structural conditions, teachings, research, health care as well
      as general questions about the situation of the discipline. All 35 addressed
      departments and institutes of Medical Psychology in Germany took part in the
      situation analyses of the subject and responded to a questionnaire. The results
      indicate strengths and weaknesses of the current situation of the discipline and
      will be discussed in terms of research, teaching, and clinical work.

PMID- 14661154
TI  - [Psychosomatic and medical psychology: shift and drift of the publication
      practice of the academic representatives].
AB  - The publication practice of the medical-psychological and psychosomatic chairs
      was the subject of a systematic investigation for the period 1992-1996 in this
      journal. The background was the discussion about quality and qualification of the
      academic newcomers. Now, most of the German university medical schools spend the
      budget--among other criteria--in accordance with the publication practice of the
      academic representative and their coworkers. The question arises, whether and how
      the chairs have changed their publication practice in comparison for the period
      1998-2002.

PMID- 14661155
TI  - [Kurt Goldstein's and Robert Wartenberg's interpretation of Babinski's sign].

PMID- 14661156
TI  - [Babinski's reflex].

PMID- 14661157
TI  - [Morphe and function - Kurt Goldstein's understanding of the Babinski
      phenomenon].
AB  - Viewed in terms of the theory of science and medicine, one of the striking
      features characterizing the period extending from the end of the 19 (th) century
      to the first third of the 20 (th) century was the formulation of concepts of
      etiopathogenesis. Existing theories on the morphe and structure of human cells,
      tissues, and organs were enlarged by models focusing on the function of these
      elements and structures of the organism. This enlargement of etiopathogenic
      concepts, including biperspective observation, occurred in the fields of internal
      medicine (Gustav von Bergmann), psychiatry (Erwin Straus), and neurology (Kurt
      Goldstein). In the light of Goldsteins's understanding of the Babinski
      phenomenon, the present paper seeks to show what fundamental questions spring
      from a theory of the human organism that takes into account both morphe and
      structure and function. Studies of historical models of this kind are both
      meaningful and justified in that they include constructs and guiding theoretical
      principles (like, for instance, biperspective access to the patient and his/her
      disease) which are of immediate relevance in addressing problems with which
      psychosomatics and medicine are challenged today.

PMID- 14661158
TI  - [Avellis' syndrome in brainstem infarctions].
AB  - In 1891 Georg Avellis described a so-called "laryngeal hemiplegia" that can be
      caused by peripheral lesions of the vagal and glossopharyngeal nerves and rarely
      by infarctions of the medulla oblongata, thus representing a classical brainstem
      syndrome. In this study we describe two patients with an Avellis' syndrome caused
      by brainstem ischemia. Contemporary publications about Avellis' syndrome in
      brainstem lesions seem to be very inhomogenous. They report various diseases with
      unilateral laryngeal palsy due to nucleus ambiguus lesions with diverse
      additional neurological symptoms. We conclude that according to Avellis' original
      description only the combination of ipsilateral palatolaryngeal paresis and
      contralateral hemiparesis and/or hemihypesthesia should to be interpreted as
      Avellis' syndrome.

PMID- 14661159
TI  - [Alcohol and drugs and their relation to criminal recidivism].
AB  - This report assesses the influence of alcohol- and drug- induced disorders on
      criminal recidivism. A sample of 185 delinquents was examined for their criminal
      responsibility in the department of forensic psychiatry in the years 1992 and
      1993. Official criminal records were obtained in December 2001. 27.3 % of the
      delinquents with alcohol abuse, 47.3 % with drug abuse and 47.2 % with a family
      history of alcohol abuse recidivated with a crime. 50 % of the individuals with
      an own alcohol- and drug abuse together with a family history of alcohol abuse
      recidivated. 62.5 % of offenders with both, own drug abuse and an alcohol abuse
      in their family history re-offended. The co-occurrence of both, own drug abuse
      and a family history of alcohol abuse is highly correlated with criminal
      recidivism and should be considered in treatment and aftercare programs.

PMID- 14661160
TI  - [The social understanding of Eugen Bleuler - his viewpoint outside of the
      psychiatric clinic].
AB  - Based on writings from different periods in the life of Eugen Bleuler, the
      present work represents a consistent recognizable concept of ethics, social order
      and race hygiene in his scientific work. These subjects are set by Bleuler in a
      more general connection of nature and culture; it can be shown that the
      scientific understanding of social and cultural phenomena is founded on
      principles which can be easily identified by looking at nature. Bleuler's
      position is a clear-cut deterministic and materialistic one; the crisis of the
      post-world-war era can be solved only by rational reasonable ethics rules of a
      science applied on social questions. Bleuler outlines the general importance of
      race hygiene; practical consequences of this position remain unaffected.
      Euthanasia is to be planed in certain cases of difficult and incurable disease -
      including also mental illness; mental deficiency as such does not legitimize a
      such step yet.

PMID- 14661161
TI  - [Tratment of primary brain tumors].

PMID- 14661162
TI  - [New aspects in pain research at Bayer].
AB  - Considerable advances in the fields of molecular biology and pain research during
      the last decade has led to the identification of a wide range of pharmacological
      targets for new analgesics. Genes of interesting targets may be regulated either
      upwards or downwards under pathophysiological, i. e. inflammatory or neuropathic
      pain conditions. Targets exclusively expressed in terms of tissues relevant for
      pain transmission, are potential promising candidates for the generation of
      analgesics devoid of serious side-effects. Especially those targets that are
      expected to be essential for the development and maintenance of a number of pains
      offer the opportunity to define courses of treatment for patients with a variety
      of different symptoms and causes. Modern drug-development is based on the
      identification of compounds directed against these specific targets. In a high
      throughput screening procedure, all substances of our drug library (about 1
      million) are examined for their effects on this specific molecular mechanism.
      Predicted pain-relieving effects are then identified by a screening cascade where
      selected drugs are tested for their activity in in-vitro assays on isolated
      neurons, tissues or recombinant cell lines. The final validation of a drugs'
      antihyperalgetic or antiallodynic properties is carried out in the relevant
      animal models of chronic pain, which mirror the clinical situation as much as
      possible. Compounds being more efficient or having an improved side effect
      profile in these models than medications currently available (and which are
      toxicologically harmless) are interesting candidates for clinical development.

PMID- 14661163
TI  - A novel syndrome combining thyroid and neurological abnormalities is associated
      with mutations in a monocarboxylate transporter gene.
AB  - Thyroid hormones are iodothyronines that control growth and development, as well
      as brain function and metabolism. Although thyroid hormone deficiency can be
      caused by defects of hormone synthesis and action, it has not been linked to a
      defect in cellular hormone transport. In fact, the physiological role of the
      several classes of membrane transporters remains unknown. We now report, for the
      first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located
      on the X chromosome, that encodes a 613-amino acid protein with 12 predicted
      transmembrane domains. The propositi of two unrelated families are males with
      abnormal relative concentrations of three circulating iodothyronines, as well as
      neurological abnormalities, including global developmental delay, central
      hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and
      impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype
      and no neurological defects. These findings establish the physiological
      importance of MCT8 as a thyroid hormone transporter.

PMID- 14661164
TI  - Combined electric field and gap junctions on propagation of action potentials in
      cardiac muscle and smooth muscle in PSpice simulation.
AB  - Propagation of action potentials in cardiac muscle and smooth muscle were
      simulated using the PSpice program. Excitation was transmitted from cell to cell
      along a strand of 6 cells (cardiac muscle) or 10 cells (smooth muscle) either not
      connected (control) or connected by low-resistance tunnels (gap-junction
      connexons). A significant negative cleft potential (V(jv) ) develops in the
      narrow junctional cleft when the pre-JM fires. V(jc) depolarizes the
      postjunctional membrane (post-JM) to threshold by a patch-clamp action. With few
      connecting tunnels, cell-to-cell transmission by the EF mechanism was
      facilitated. With many tunnels, propagation was dominated by the low-resistance
      mechanism, and propagation velocity (theta) became very fast and
      nonphysiological. In conclusion, when the 2 mechanisms for cell-to-cell transfer
      of excitation were combined, the two mechanisms facilitated each other in a
      synergistic manner. When there were many connecting tunnels, the tunnel mechanism
      was dominant.

PMID- 14661165
TI  - Experimental study of the effect of the vagus nerve on atrial electrical
      remodeling.
AB  - Recent studies have shown that rapid atrial activation causes atrial electrical
      remodeling (AER), which recovers quickly following withdrawal of stimulation. The
      underlying mechanisms, however, are incompletely understood. The purpose of the
      present study, therefore, was to characterize the effect of the vagus on AER as
      well as define possible mechanisms of the phenomenon. Eight dogs were used in the
      study for 3 consecutive protocols. In the first, the dogs were subjected to
      atrial pacing at 800 ppm for 7 hours. Every hour, pacing was interrupted for a
      short time and atrial effective refractory period (AERP) was measured at 6 sites.
      The rapid atrial pacing was then discontinued and the electrophysiological study
      was repeated every hour for another 7 hours. Time-domain parameters of heart rate
      variability (HRV) were also computed 1 hour before pacing as well as each of 7
      hours after the rapid atrial pacing protocol. The second program was performed
      two weeks after the first; 0.04 mg/kg of atropine was administered intravenously
      30 min before pacing, and then 0.007 mg/kg was added at each hour. Parameters of
      HRV were not evaluated. Finally, the 8 dogs were subjected to the third protocol
      2 weeks after completion of the second; 0.2 mg/kg of propranolol was given
      intravenously 30 min before pacing, and 0.04 mg/kg was added at each hour. The
      dispersion of AERP (dAERP) was calculated as, maximum AERP minus minimum AERP.
      There was a prompt decrease in AERP as the result of pacing (P<.05), but dAERP
      did not change significantly. The AERP recovered quickly, and dAERP increased
      from 21 +/-5.3 ms to 40 +/- 7.4 ms (P<.05) after cessation of pacing. At the same
      time, the parameters of HRV increased (P<.05) after cessation of pacing. The AERP
      increased from 128 +/- 12 ms to 135 +/- 12 ms and from 127 +/- 12 ms to 142 +/-
      14 ms (P<.05) after vagal and autonomic blockade. However, AERP decreased during
      pacing (P<.05) with vagal or autonomic blockade, but dAERP did not change
      significantly during or after pacing. These results suggest that vagal and
      autonomic blockade can not prevent AER, but a high vagal tone is associated with
      a high dAERP during recovery from AER, indicating that the vagus and sympathetic
      have a synergistic effect on the refractory period.

PMID- 14661166
TI  - Electrophysiologic effects of mental stress in healthy subjects: a comparison
      with epinephrine infusion.
AB  - Mental stress has been associated with serious cardiac arrhythmias, including
      ventricular tachycardia and ventricular fibrillation. The purpose of this study
      was to assess cardiac electrophysiologic effects of mental stress and compare
      them with those of epinephrine infusion. Ten healthy male volunteers
      participated. Electrophysiologic and hemodynamic variables were measured at
      baseline, during mental stress produced by Stroop's color word conflict test and
      during epinephrine infusion at 2 rates (0.025 micromol/kg/min and 0.3
      micromol/kg/min). Mental stress produced significant effects on the
      electrophysiologic properties of the heart with shortening of all measured
      electrophysiologic variables except atrial, most markedly those of the sinus and
      the atrioventricular nodes. The effects on the right ventricular myocardium and
      the His-Purkinje conduction system were less pronounced. During infusion of
      epinephrine, corresponding effects could only be reproduced at a much higher
      plasma level. Circulating epinephrine apparently plays a minor role as a mediator
      of mental stress effects on the heart.

PMID- 14661167
TI  - Atrioventricular conduction variability in coronary patients.
AB  - Variability in atrioventricular (AV) conduction has been described in healthy
      subjects, whereas data for coronary patients are lacking. This study was designed
      to evaluate AV conduction variability in patients with stable coronary artery
      disease. Beat-to-beat PR interval variability with 5-minute resting high
      resolution electrocardiogram recordings was measured in 30 men (mean age 50.9
      years) with effort angina pectoris and 30 age-matched men without clinically
      evident coronary artery disease (controls). To evaluate the degree of coronary
      artery disease in coronary patients, coronary angiography was performed. Coronary
      patients displayed significantly lower values of PR interval variability compared
      with control subjects (P <.001). Relative PR variability (PRPP) index, calculated
      as the ratio of normalized PR variability to cycle length variability, was
      significantly higher in coronary patients (P =.001) and did depend on the degree
      of coronary artery disease. We concluded that coronary artery disease is
      associated with decreased beat-to-beat fluctuations in AV conduction. Increased
      relative PR variability index suggests inhomogeneous AV conduction in stable
      coronary atherosclerosis.

PMID- 14661168
TI  - Comparison of P-wave duration and dispersion in patients aged > or =65 years with
      those aged < or =45 years.
AB  - P-wave dispersion (PWD) is a new electrocardiographic marker that reflects
      discontinuous and inhomogeneous propagation of sinus impulses, which has been
      studied in some cardiac conditions as a useful predictor of paroxysmal atrial
      fibrillation (AF). The aim of the peresent study was to compare P-wave duration
      and PWD in patients < or =45 versus > or =65 years of age. The study consisted of
      2 groups. Group I included 118 patients aged > or =65 years (86 men, 32 women,
      mean age= 69 +/- 4 years). Group II included 72 patients aged < or =45 years (53
      men, 19 women, mean age= 41 +/- 4 years). All patients were selected from those
      who were undertaken coronary angiography in our hospital with a suspicion of
      coronary artery disease and detected as having angiographically normal coronary
      arteries. All patients were undertaken transthoracic echocardiography to evaluate
      the presence of any structural and functional cardiac abnormality. Maximum and
      minimum P-wave durations and PWD were calculated from 12-lead surface
      electrocardiogram. Maximum P-wave duration and PWD were significantly higher in
      group I patients than in group II patients (P <.001). However, there was no
      statistically significant difference between group I patients and group II
      patients regarding minimum P-wave duration (p=0.9). Left atrial diameter, left
      ventricular wall thicknesses, mitral A velocity, deceleration time and isovolumic
      relaxation time were significantly higher in group I patients than in group II
      patients. However, mitral E velocity were significantly lower in group I patients
      than in group II patients. A significant positive correlation was detected
      between PWD and age, left atrial diameter, mitral A velocity, deceleration time
      and isovolumic relaxation time. In addition, we found a significant negative
      correlation between PWD and mitral E velocity. PWD, indicating increased risk for
      paroxysmal AF, was found to be significantly higher in patients > or =65 years of
      age than in those < or =45 years of age. Further prospective studies that include
      larger series and long term follow-up are needed to clarify the clinical utility
      of PWD as a predictor of increased risk for paroxysmal AF in old patients.

PMID- 14661170
TI  - Prognostic value of heart rate variability in patients with hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) have been reported to display impaired heart
      rate variability, although little is known regarding its prognostic value. By
      using fast Fourier transformation of 24-hour Holter recordings in 73 HCM patients
      at a stable clinical condition, we computed 4 spectral components: very low
      frequency, low frequency, high frequency, and total power. During 28 months, 7
      HCM patients experienced death or acquired hospitalization for heart failure.
      Sudden death did not occurred. High frequency component was lower in HCM patients
      with cardiac events than that in patients without cardiac events (3.78 +/- 0.66
      vs. 4.43 +/- 0.92 In(ms(2)), P =.045). There were no significant differences in
      other heart rate variability variables between HCM patients with and without
      cardiac events. In multivariate analysis, high frequency component remained to be
      an independent predictor of cardiac events (relative risk=0.10, 95% CI 0.01-0.73,
      P =.023). Heart rate variability analysis is predictive of heart failure in our
      cohort of HCM patients, whereas its predictive value of sudden death remains
      unclear.

PMID- 14661169
TI  - Electrocardiographic predictors of failure and recurrence in patients with
      idiopathic right ventricular outflow tract tachycardia and ectopy who underwent
      radiofrequency catheter ablation.
AB  - This study reports new electrocardiographic (ECG) predictors of radiofrequency
      catheter ablation failure and recurrence in idiopathic right ventricular outflow
      tract (RVOT) ventricular tachycardia (VT) or ectopy based on 91 consecutive
      patients. Procedural success and failure rates were 85% (77/91) and 15% (14/91),
      respectively. Twenty three percent (18/77) had recurrence during the follow-up
      period of 1 to 120 months (mean 56 +/- 31 months). Baseline RVOT VT/ectopy on 12
      lead ECG taken prior to ablation from 91 patients were retrospectively analyzed.
      Ablation performed with RVOT ectopy (isolated ectopies, bigeminy, trigeminy, or
      couplets) as template arrhythmia was more likely to fail (30% vs. 8%, P =.02) as
      opposed to RVOT VT (sustained or nonsustained). VT/ectopy-QRS morphology
      variation was more observed in failed ablations (36% vs. 7%, P =.001).
      Significantly wider mean VT/ectopy QRS in leads I, II, AVR, V2, V3, V5, and V6
      were noted in failed ablation group. Mean R wave amplitude reached statistical
      significance only in lead II (22.0 +/- 5.1 mV for failed vs. 17.8 +/- 5.2 mV for
      successful outcomes; P =.009). QRS morphologic variation (47% vs. 16%; P =.009)
      was the only statistically significant ECG to be more common in patients with
      arrhythmia recurrence. In conclusion, ablation with ectopy over VT as template
      arrhythmia, presence of QRS morphologic variation, wider mean QRS width, and
      taller mean R-wave amplitude in lead II were identified ECG predictors of failed
      RVOT VT/Ectopy ablation. The only ECG predictor of recurrence was the presence of
      RVOT VT or ectopy QRS morphologic variation.

PMID- 14661172
TI  - Recording undetected P waves in a case of heart transplant with a new bipolar
      system.
AB  - Using a new electrocardiographic lead (L-P lead), we recorded undetected P waves
      in a post heart-transplant patient. This case shows another application of a
      noninvasive method, a modification of Einthoven's bipolar leads, used to approach
      undetermined rhythms.

PMID- 14661171
TI  - Ventricular fibrillation during anesthesia in association with J waves in the
      left precordial leads in a child with coarctation of the aorta.
AB  - A 14-year-old boy with coarctation of the aorta who showed repeat ventricular
      fibrillation during anesthesia, and ultimately sudden cardiac death in school, is
      presented. Electrocardiography showed J waves in the left precordial leads, which
      became prominent after an episode of ventricular fibrillation. While some of the
      clinical features and electrophysiological findings were similar to those seen in
      Brugada syndrome, others were inconsistent. J waves in the left precordial leads
      should be recognized as a possible waveform change inducing ventricular
      fibrillation predominantly at rest.

PMID- 14661173
TI  - Atrial escape-capture bigeminy in dominant atrial rhythm with 2:1 exit block.
AB  - A 27-year-old woman with atrial bigeminy is reported in whom long PP intervals
      alternate with short PP intervals. All P waves are negative in lead II and all PR
      intervals measure 0.12 s. In the 12-lead electrocardiogram, however, these P
      waves were definitely different in configuration from each other, and were
      divided into two groups. Namely, these negative P waves are divided into those of
      dominant atrial rhythm J1 with 2:1 exit block, and those of atrial escape J2.
      Long J1-J2 intervals alternate with short J2-J1 intervals. These
      electrocardiographic findings show the presence of atrial escape-capture
      bigeminy. Such atrial escape-capture bigeminy in dominant atrial rhythm with 2:1
      exit block has never been reported before.

PMID- 14661174
TI  - Apparent bradycardia-dependent right bundle branch block associated with atypical
      atrioventricular Wenckebach periodicity as a possible mechanism.
AB  - The Holter monitor electrocardiogram was taken from a 15-year-old male athlete.
      Intermittent right bundle branch block frequently occurred at rest. When sinus
      cycles gradually lengthened, sinus impulses were conducted to the ventricles with
      right bundle branch block (RBBB) in succession. When, thereafter, sinus cycles
      gradually shortened, sinus impulses were conducted without RBBB. However, it
      seems that these findings do not show true bradycardia-dependent RBBB. Atypical
      atrioventricular Wenckebach periodicity was occasionally found in which sudden
      shift from the period of comparatively short PR intervals to the period of long
      PR intervals occurred. In the Wenckebach periodicity, when a QRS complex occurs
      after a much longer pause, RBBB was not found, while when it occurs after a much
      shorter period, RBBB was found. This suggests that this case may be apparent
      bradycardia-dependent RBBB, namely, a form of tachycardia-dependent RBBB. This is
      the first report suggesting apparent bradycardia-dependent bundle branch block
      associated with gradual lengthening of sinus cycles, as a possible mechanism.

PMID- 14661177
TI  - Ganciclovir nucleotides accumulate in mitochondria of rat liver cells expressing
      the herpes simplex virus thymidine kinase gene.
AB  - BACKGROUND: Ganciclovir exhibits broad-spectrum activity against DNA viruses such
      as cytomegaloviruses, herpes simplex viruses, varicella-zoster virus, Epstein
      Barr virus and human herpes virus-6. Ganciclovir is widely applied for anti
      herpetic treatment, cytomegalovirus prophylaxis after organ transplantation, and,
      more recently, in experimental gene therapy to eradicate cycling cells that
      express the herpes simplex virus thymidine kinase gene. Although ganciclovir
      supposedly acts as a chain terminator, there is compelling evidence demonstrating
      the presence of ganciclovir, but not of acyclovir, incorporated internally into
      DNA, leaving the precise mechanism by which ganciclovir inhibits DNA synthesis
      enigmatic. METHODS: To study the potential involvement of mitochondria in the
      ganciclovir nucleotide cytotoxicity, we used adenovirus-mediated gene transfer to
      express herpes simplex virus thymidine kinase in rat liver and administered
      ganciclovir 2 days post-infection. The integrity and function of mitochondria in
      the rat liver cells were evaluated by several techniques. In addition, we
      analyzed the nucleotide pools in cellular extracts and in isolated mitochondria.
      RESULTS: We show that ganciclovir nucleotides are abundantly present in the
      mitochondria of rat livers that express the HSVtk gene. Already 48 h after
      administration, 10-30% of the total mitochondrial nucleotide pool consists of
      ganciclovir nucleotides. Their presence is correlated with a lower amount of
      mitochondrial DNA, a reduced mitochondrial-membrane potential, morphological
      abnormalities, and liver dysfunction. CONCLUSIONS: These data provide evidence
      for the involvement of mitochondria in the hepatotoxicity of the HStk/ganciclovir
      combination. This may explain the toxicity of the HSVtk/gancilovir combination in
      some metabolically active but non-proliferating cells, such as liver cells. This
      toxicity limits the applicability of this enzyme/prodrug combination.

PMID- 14661176
TI  - Comparison of wild-type and class I integrase mutant-FIV vectors in retina
      demonstrates sustained expression of integrated transgenes in retinal pigment
      epithelium.
AB  - BACKGROUND: In neonatal and adult rodent retina, substantial lentiviral vector
      expression has been detected primarily in retinal pigment epithelium (RPE),
      except in very young animals (2-5 days post-natal). In non-retinal tissues,
      studies of lentiviral vectors have utilized various controls. Among the most
      stringent are class I integrase mutants, which selectively block the integration
      reaction while leaving all other gag/pol-encoded functions intact. For HIV-1
      vectors injected into brain, these have been used to simultaneously control for
      pseudotransduction and verify that long-term expression requires integration.
      Such experiments compare particles that differ only in a single amino acid within
      a single enzyme that forms a very small molar fraction of the virion. Class I
      integrase mutants have not been described for feline immunodeficiency virus (FIV)
      integrase, or tested in the eye for any lentiviral vector. METHODS: We compared
      subretinally and intravitreally injected FIV vectors and followed animals for up
      to 7 months, a duration that exceeds prior studies. We also compared the wild
      type (WT) vector with one incorporating a single class I amino acid mutation in
      FIV integrase (D66V). A mock vector (packaging construct absent) was an
      alternative control. All vectors were vesicular stomatitis virus glycoprotein G
      (VSV-G)-pseudotyped and were injected on day 7 of life. One group of animals
      received either subretinal or intravitreal injections of WT vector in the right
      eyes. Control left eyes were injected with mock vector. These animals were
      sacrificed at 2 or 7 days post-injection. A second group received subretinal
      injections of either WT vector or equivalent D66V vector (reverse transcriptase
      normalized to WT), and were analyzed after 2, 3 and 7 months. All eyes were
      scored for marker gene (beta-galactosidase) expression by an observer blinded to
      vector assignments. RESULTS: Subretinal FIV vector injections were much more
      effective than intravitreal injections. The RPE was the principal retinal layer
      transduced by the WT vector, and at least 50% of the area of the retina expressed
      the marker gene at 3 and 7 months. Occasional cells in inner retinal layers also
      expressed beta-galactosidase at these time points. The sustained retinal
      expression produced by subretinally injected vector was blocked by the D66V
      mutation. CONCLUSIONS: These results show that class I integrase mutant FIV
      vectors are useful control vectors, and that VSV-G-pseudotyped FIV vectors
      produce extensive retinal expression for at least 215 days, the longest duration
      yet reported for lentiviral vectors in retina. Transgene expression is mostly
      restricted to RPE after post-natal day 7 in rats, suggesting that FIV vectors
      could be used to target RPE for gene therapy.

PMID- 14661178
TI  - Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic
      cells to treat a radiation-induced multi-organ failure syndrome.
AB  - BACKGROUND: Recent studies have suggested that ex vivo expansion of autologous
      hematopoietic cells could be a therapy of choice for the treatment of bone marrow
      failure. We investigated the potential of a combined infusion of autologous ex
      vivo expanded hematopoietic cells with mesenchymal (MSCs) for the treatment of
      multi-organ failure syndrome following irradiation in a non-human primate model.
      METHODS: Hematopoietic cells and MSCs were expanded from bone marrow aspirates.
      MSCs were transduced with the gene encoding for the green fluorescent protein (e
      GFP), in order to track them following infusion. Twelve animals were studied.
      Nine animals received total-body irradiation at 8 Gy from a neutron/gamma source
      thus resulting in heterogeneous exposure; three animals were sham-irradiated. The
      animals were treated with expanded hematopoietic stem cells and MSCs, expanded
      hematopoietic stem cells alone, or MSCs alone. Unmanipulated bone marrow cell
      transplants were used as controls. RESULTS: Depending on the neutron/gamma ratio,
      an acute radiation sickness of varying severity but of similar nature resulted.
      GFP-labeled cells were found in the injured muscle, skin, bone marrow and gut of
      the treated animals via PCR up to 82 days post-infusion. CONCLUSIONS: This is the
      first evidence of expanded MSCs homing in numerous tissues following a severe
      multi-organ injury in primates. Localization of the transduced MSCs correlated to
      the severity and geometry of irradiation. A repair process was observed in
      various tissues. The plasticity potential of the MSCs and their contribution to
      the repair process in vivo remains to be studied.

PMID- 14661179
TI  - In vivo knockdown of gene expression in brain cancer with intravenous RNAi in
      adult rats.
AB  - BACKGROUND: Gene silencing in mammalian cells is possible with RNA interference
      (RNAi) with expression plasmids that encode for short hairpin RNAs (shRNA) that
      hybridize to a specific sequence within a target mRNA. The limiting factor in
      developing RNAi therapeutics in mammals is the gene delivery system. METHODS: The
      present studies describe the production of anti-luciferase shRNA expression
      plasmids, which are encapsulated in the interior of 85 nm pegylated
      immunoliposomes (PILs). C6 rat glioma cells, permanently transfected with the
      luciferase gene, are implanted in the caudate-putamen nucleus of adult rats,
      which produces luciferase-expressing intracranial brain cancer. The PILs are
      targeted across the blood-brain barrier and across the tumor cell membrane in
      vivo with a monoclonal antibody (MAb) to the rat transferrin receptor (TfR). The
      TfRMAb is tethered to the tips of 1-2% of the poly(ethylene glycol) strands
      conjugated to the surface of the liposome. RESULTS: The TfRMAb-targeted PILs
      inhibit luciferase gene expression in the brain cancer by 90%, and this effect
      persists for at least 5 days after a single intravenous injection of 10 micro
      g/rat of plasmid DNA. RNAi therapy directed against the luciferase gene caused no
      change in expression of tumor gamma-glutamyl transpeptidase. Targeting the empty
      expression plasmid with the TfRMAb-PIL resulted in no change in luciferase
      activity in the brain cancer in vivo. CONCLUSIONS: In vivo RNAi is enabled with a
      new form of gene delivery system that encapsulates expression plasmids in PILs,
      which are targeted to distant sites based on the specificity of a receptor
      specific monoclonal antibody. The combined application of the PIL gene delivery
      system and RNAi expression plasmids enables gene silencing in remote sites such
      as brain cancer in mammals after intravenous administration.

PMID- 14661180
TI  - Enhancement of ultrasound-mediated gene transfection by membrane modification.
AB  - BACKGROUND: Ultrasound-mediated gene transfection (USMGT) with an echo contrast
      agent could be a new promising physical method of triggering localized gene
      delivery, but the effect is still modest. The aim of this study is to devise a
      method to improve efficiency of USMGT. We examined the effect of lidocaine and
      different temperatures on USMGT, each of which is a known membrane modifier,
      since the plasma membrane can be considered a site of action in USMGT. METHODS:
      We observed the effect of lidocaine (0.01, 0.1 or 1.0 mM) and different
      temperatures (7, 20, 37, 42 or 44 degrees C) on USMGT (1 MHz, 3.6 W/cm(2)
      (I(SATA)) and 20 s exposure) in the presence of Levovist (10 mg/ml). At 20 h
      after sonication, transfection efficiency was evaluated by luciferase assay.
      Membrane fluidity was examined by fluorescence polarization measurement.
      Cavitational activity was measured by ESR spin trapping with 5,5-dimethyl-1
      pyrroline N-oxide. The number of cells transfected with the GFP gene was counted
      under a fluorescence microscope. RESULTS: Lidocaine (1 mM) and heat (42-44
      degrees C) significantly increased luciferase expression approximately 18-fold
      and 19-fold higher than Levovist only. Both treatments were shown to increase
      membrane fluidity; in addition, heat enhanced a cavitational effect. It was
      confirmed by an experiment using the GFP gene that increase in luciferase
      expression was due to the increase in number of cells. CONCLUSIONS: This
      enhancement could be useful for ultrasound-mediated gene therapy in the future
      since both treatments for membrane modification could be directly applied to the
      living body.

PMID- 14661181
TI  - Engineering of technetium-99m-binding artificial receptors for imaging gene
      expression.
AB  - BACKGROUND: Optimization of gene therapy protocols requires accurate and non
      invasive quantification of vector delivery and gene expression. To facilitate non
      invasive imaging of gene expression, we have genetically engineered 'artificial
      receptors', i.e. membrane proteins that bind (99m)Tc-oxotechnetate ((99m)TcOT)
      via transchelation from a complex with glucoheptonate. The latter is a component
      of a widely used clinical imaging kit. METHODS: The engineered marker proteins
      were designed as type I and II membrane proteins and consisted of (1) an
      (99m)TcOT-binding domain, metallothionein (MT), and (2) a membrane-anchoring
      domain. Engineered constructs were used for transfection of COS-1 and 293 cells;
      the expression of mRNA was verified by RT-PCR. RESULTS: Immunofluorescent
      analysis, cell fractionation and immunoblotting revealed expression of marker
      proteins on plasma membrane. Transfection of cells resulted in strong positive
      staining of plasma membrane with anti-His-tag antibodies. Scintigraphic imaging
      in vitro confirmed the ability of transfected cells to bind (99m)TcOT. The
      fraction of bound radioactivity reached a peak (3.53%) when 0.93 MBq (99m)TcOT
      was added to transfected COS-1 cells. The experiment-to-control signal ratio was
      equal to 32 at the same added dose. CONCLUSIONS: (1) Both types of engineered
      'artificial receptors' were expressed on the surface of eukaryotic cells; (2)
      marker proteins were functional in binding (99m)TcOT; and (3) type II membrane
      proteins were more efficient in binding (99m)TcOT than type I proteins. We
      anticipate that the developed approach could be useful for 'tagging' transfected
      cells with (99m)TcOT enabling imaging of tracking in vivo transduced cells or
      cell therapies.

PMID- 14661182
TI  - Novel macrolide-adjustable bidirectional expression modules for coordinated
      expression of two different transgenes in mice.
AB  - BACKGROUND: Precise control of transgene expression is essential for a variety of
      applications ranging from gene-function analysis, biopharmaceutical manufacturing
      to next-generation molecular interventions in gene therapy and tissue
      engineering. The regulation of gene expression is currently a key issue for
      clinical implementation of gene-therapy-based treatments since desired transgene
      expression may need to be maintained within a narrow therapeutic window for
      successful treatment of a particular human disease. METHODS: We have designed a
      novel bidirectional expression module that enables adjustable coregulation of two
      different transgenes in response to clinical doses of macrolide antibiotics. A
      bidirectional macrolide-responsive promoter consisting of a central operator
      module (ETR) specific for the macrolide-dependent transactivator (ET1) is flanked
      by two minimal promoters (P(hCMVmin); P(hsp70min)) which drive expression of two
      divergently oriented transgenes. Macrolide antibiotics modulate the binding
      affinity of ET1 to ETR and adjust expression of both transgenes to desired
      levels. RESULTS: Bidirectional expression configurations enabled excellent
      macrolide-adjustable coregulation profiles of two secreted reporter genes or one
      vector-based autoregulated fine-tuning of a single transgene in various
      transgenic rodent and human cell lines. Following implantation of
      microencapsulated CHO-K1 cell derivatives transgenic for macrolide-controlled
      bidirectional expression of erythropoietin (EPO) and the human secreted alkaline
      phosphatase (SEAP) intraperitoneally into mice, serum EPO and SEAP levels could
      be coadjusted to desired levels by administration of different erythromycin
      doses. CONCLUSIONS: Based on their in vivo compatibility, the versatile
      bidirectional and macrolide-responsive expression modules represent an important
      advancement on the way to implementing targeted and conditional molecular
      interventions into a clinical reality.

PMID- 14661183
TI  - Increased in vitro and in vivo transgene expression levels mediated through cis
      acting elements.
AB  - BACKGROUND: Gene therapy for neurodegenerative diseases depends critically on the
      vector system to direct sustained and stable expression of the transgene. It is,
      however, a commonly observed phenomenon that transgene expression from currently
      available vectors is down-regulated following ex vivo gene transfer to the
      central nervous system (CNS). In an attempt to circumvent this problem, we have
      systematically evaluated the potential of different cis-acting elements to
      increase and stabilize transgene expression in vitro and after grafting of
      engineered cell lines to the CNS. METHODS: Plasmid vector constructs
      incorporating Woodchuck hepatitis post-transcriptional regulatory element (WPRE),
      cHS4 insulator elements and/or the translational enhancer element SP163 were
      produced. Stable, polyclonal cultures of HiB5 cells were generated by
      transfection with reporter constructs, and in vitro transgene mRNA and protein
      levels were determined. Finally, HiB5 clones engineered to express the enhanced
      green fluorescent protein (EGFP) were grafted to the rat striatum and expression
      levels were evaluated. RESULTS: Inserting the WPRE element downstream of the open
      reading frame (ORF) of a reporter gene and flanking the transcriptional unit with
      cHS4 insulator elements significantly increased protein and mRNA expression
      levels. Surprisingly, the SP163 element, previously reported to be a
      translational enhancer, apparently did not promote any translational enhancing
      activity. Furthermore, the SP163 element exerted a negative effect on
      transcription. The ability of cHS4 and WPRE elements to stabilize in vivo
      transgene expression was demonstrated by transplantation of HiB5 clones
      containing expression constructs into the rat striatum. CONCLUSION: The data
      suggest that incorporating cis-acting elements in gene therapy vectors may result
      in improvements to currently available therapeutic vectors.

PMID- 14661186
TI  - Insomnia causes, consequences, and therapeutics: an overview.
AB  - There is growing interest in insomnia both from the perspective of recent
      advances in clinical management as well as research aimed at elucidating its
      pathophysiology. This theoretical overview of insomnia describes the negative
      impact, etiological considerations, and pharmacological and behavioral treatments
      for the disorder, with an emphasis on areas receiving increased research
      attention. Insomnia, the most prevalent sleep disorder, affects 10-15% of the
      general population. In population-based studies severe insomnia has been shown to
      last for a median of 4 years. In addition, insomnia has a significant negative
      impact on an individual's work, physical, and social performance as well as
      overall quality of life. Furthermore, the economic cost of insomnia related to
      lost productivity, work-related accidents, absenteeism, and health-care costs are
      enormous. There is increasing evidence linking the precipitation of insomnia to
      stress, and converging evidence from cognitive, endocrine, neurological, and
      behavioral domains provide clear evidence for hyper-arousal in insomnia. However,
      there remains no consensus regarding the specific etiological mechanisms of this
      disorder. Although the pathophysiology of primary insomnia remains an enigma,
      numerous treatments both pharmacological and behavioral have been developed and
      found to be efficacious in controlled studies. Despite the wide availability of
      pharmacological treatments and increased knowledge of behavioral interventions,
      the vast majority of individuals with insomnia do not appear to be receiving
      adequate treatment. The inadequate treatment of insomnia leads to several
      important and under-recognized consequences including subsequent development of
      psychiatric disease and increased substance use.

PMID- 14661187
TI  - Fear of loss of vigilance: development and preliminary validation of a self
      report instrument.
AB  - We describe the development and initial validation of the Fear of Loss of
      Vigilance Questionnaire (FLOVQ). Recent investigations indicate that individuals
      with nocturnal panic (NP) demonstrate increased anxiety and panic in response to
      meditative relaxation and imagined hypnosis, compared to those with daytime panic
      (DP) only, suggesting that NP individuals fear situations that involve a loss of
      vigilance (e.g., relaxation, fatigue and altered states of consciousness). The
      FLOVQ was designed to assess this construct and was tested in five non-clinical
      samples and one clinical sample. The 14-item instrument demonstrated good
      internal consistency and test-retest reliability. Non-clinical respondents who
      experienced NP endorsed greater fear of loss of vigilance than non-panickers;
      those who only experienced DP did not differ from the other groups. By contrast,
      on measures of trait and state anxiety, and anxiety sensitivity, both panic
      groups scored higher than non-panickers, suggesting that these latter measures
      were related to broader factors pertaining to a general tendency to panic versus
      a specific factor associated with NP. No group differences were found between NPs
      and DPs in either the non-clinical or the clinical sample, suggesting that fear
      of loss of vigilance may be a vulnerability factor for the development of NP and
      that the FLOVQ has more utility as a research rather than as a clinical
      instrument.

PMID- 14661188
TI  - Sleep in post-traumatic stress disorder and panic: convergence and divergence.
AB  - Disturbed sleep is a common clinical problem in anxiety disorders, particularly
      in patients with post-traumatic stress disorder (PTSD) and panic disorder (PD).
      Several studies have attempted to validate the subjective sleep complaints of
      these disorders using laboratory polysomnography. These attempts, typically
      focusing on PTSD or PD independently, have demonstrated inconsistent results. To
      our knowledge, no such studies have attempted to directly compare and contrast
      sleep disturbances in PTSD and PD together. Our review of the studies of
      subjective sleep disturbances, sleep architecture, and sleep-related biologic
      phenomena suggests that a comparative characterization of sleep disturbances in
      these two disorders is timely. Such an inference is based on our identification
      of several areas of convergence and divergence between PTSD and PD found in the
      published literature, as well as our own preliminary investigations.
      Specifically, PTSD and PD seem to converge on several sleep-related parameters,
      namely, sleep quality, presence of episodic parasomnias, and movement time. They
      also appear to diverge in other important sleep-related areas such as respiratory
      disturbances and the particular phenomenological nature of episodic parasomnias,
      namely nightmares or nocturnal panic attacks. Investigations focusing on such
      overlapping phenomena may provide groundwork for further elucidation of central
      fear systems underlying these two disorders. Additionally, such sleep studies
      have the potential to provide important insights into ongoing efforts to develop
      a cohesive conceptual framework into the patho-physiologies of these disorders.

PMID- 14661189
TI  - Sleep respiratory concomitants of comorbid panic and nightmare complaint in post
      traumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) patients with comorbid panic disorder (PD)
      may express additive symptoms of central fear system disturbance. They endorse
      elevated levels of sleep and nightmare disturbance [Leskin GA, et al., J
      Psychiatr Res 2002;36:449-452], and demonstrate movement suppression during
      laboratory sleep [Woodward SH, et al., Sleep 2002;25:681-688]. We estimated
      respiratory rate and rate variability separately for rapid-eye movement (REM) and
      non-rapid-eye movement (NREM) sleep. Subjects were 49 Vietnam combat-related PTSD
      inpatients (11 with comorbid PD and 38 without) and 15 controls. Computer-based
      estimates of respiratory rate and variability were derived from 10 to 18 hr of
      baseline sleep collected over two or three nights. Neither rate nor rate
      variability distinguished PTSD patients with comorbid PD from those without, or
      PTSD patients from controls; however, PTSD patients failed to exhibit the
      expected differences between REM and NREM respiratory rates. Moreover, the
      difference between REM and NREM respiratory rate was inversely related to a
      continuous measure of PTSD severity. PTSD patients with trauma-related nightmare
      complaint exhibited higher sleep respiration rates over both REM and NREM sleep.
      Conversely, in addition to slowed respiration, nightmare-free patients exhibited
      reduced respiratory rate variability in REM relative to NREM sleep, which was a
      reversal of the normal pattern. These finding are discussed in light of known
      telencephalic regulatory influences upon respiration rate.

PMID- 14661190
TI  - Reactivity to imagery and nocturnal panic attacks.
AB  - We assessed psychophysiological responses to imagery of traumatic events, panic
      attacks, and loss of vigilance (i.e., being hypnotized) in participants diagnosed
      with panic disorder. Participants were either currently experiencing nocturnal
      panic or daytime panics only. It was hypothesized that nocturnal panickers would
      exhibit heightened responsivity to imagery of their worst panic and worst trauma,
      as well as being hypnotized, compared to day panickers. Using established imagery
      procedures, heart rate, skin conductance, and frontalis electromyogram were
      recorded as participants imagined each scene. Nocturnal and day panickers
      differed in their responses to the hypnosis scene only. As predicted, nocturnal
      panickers endorsed more panic symptoms in response to imagery of being
      hypnotized. Contrary to expectation, nocturnal and daytime panickers showed no
      differences in physiologic reactivity or self-reported distress to worst trauma
      or worst panic imagery. The findings are discussed with respect to the role of
      fear of loss of vigilance for nocturnal panic.

PMID- 14661191
TI  - Sleep panic attacks: a micro-movement analysis.
AB  - Earlier work by our group and others has pointed to a role for movement during
      sleep in sleep-panic attacks. Specifically, our group has reported that panic
      disorder patients, as a group, appear to move more during sleep than age-matched
      controls, whereas the subgroup of panic disorder who "panic" during sleep move
      less on the nights they experience sleep-panic attacks than they do on nights
      without sleep-panic attacks. We studied the movement of sleep-panic patients in a
      more detailed fashion with more than one sleep movement index. Fourteen patients
      with sleep-panic attacks were compared with 14 waking panic patients, 13 social
      phobic patients, and 14 normal controls. Subjects from the other groups were age
      matched to the sleep-panic group. Their comparison study night corresponded to
      the night number of the sleep-panic attack. Sleep-panic patients did move less on
      panic nights than did the normal controls on the corresponding sleep-panic night
      according to two separate sleep movement indices. Although not statistically
      significant, sleep-panic patients also moved less on their panic night than did
      either of the other anxious groups on corresponding nights. Rechtshaffen and
      Kales' Movement Time (MT) measure appears to overestimate actual min of movement
      during sleep in all subjects. The movement noted in sleep-panic patients may have
      some role in the pathophysiology of sleep-panic attacks. A possible mechanism is
      explained.

PMID- 14661192
TI  - Nocturnal panic: biology, psychopathology, and its contribution to the expression
      of panic disorder.
AB  - The latest studies on psychopathology and biology of nocturnal (or sleep) panic
      attacks and other findings related to sleep in panic disorder are reviewed. While
      some of the newer articles doubt that nocturnal panics present a more severe
      variation of panic disorder, older studies and some newer articles support this
      notion. Some studies suggest that nocturnal panic maybe also be associated with
      other, more severe pathology. This interesting syndrome, or variant of disorder,
      may have its own etiology, psychopathology, and underlying biology.

PMID- 14661193
TI  - Skin picking and sleep disturbances: relationship to anxiety and need for
      research.
AB  - Pathological excoriation (PE) or skin picking is seen in nearly 2% of patients
      attending dermatology clinics and is often associated with anxiety, stress and
      frequent help-seeking behaviors. While anxiety and stress are thought to cause
      poor sleep in the general population, not all anxious people, even those with
      disabling anxiety disorders, necessarily suffer from insomnia or other sleep
      problems. The relationship between anxiety symptoms and poor sleep, therefore,
      remains unclear and sleep quality in PE is unknown. We examined the sleep quality
      and levels of anxiety in dermatological patients with PE. Dermatological patients
      with (n = 10) and without (n = 10) PE and healthy controls (n = 10) were assessed
      on standardized and validated measures of subjective sleep quality [Pittsburgh
      Sleep Quality Index (PSQI)], anxiety (Spielberger State and Trait Anxiety
      Inventory; modified Zung Anxiety Scale), stress (Perceived Stress Scale) and work
      and social disability [Sheehan Disability Inventory subscale (SDI-4)]. Patients
      with dermatological complaints as a group reported poorer sleep quality, higher
      scores on Spielberger State and Zung anxiety, perceived stress, and SDI-4. Among
      both groups of dermatological patients, only the PE group had significantly poor
      sleep, high anxiety, and perceived stress compared to healthy controls. In the
      dermatological patients with PE, PSQI-global scores were significantly positively
      correlated to Spielberger State and Zung Anxiety scores. Dermatological patients
      with PE are more anxious and have poorer subjective sleep compared to
      dermatological patients without PE and healthy. Future research is needed to
      elucidate these relationship factors and to develop new behavioral and drug
      treatments for the management of PE.

PMID- 14661196
TI  - Switching of a spin-crossover-material incorporated in metal-organic frameworks
      by a reversible ligand-substitution reaction in the crystalline state.

PMID- 14661197
TI  - Potassium channels: symmetric, selective, and sensitive.

PMID- 14661198
TI  - The restoration of the largest archaelogical discovery--a chemical problem:
      conservation of the polychromy of the Chinese terracotta army in Lintong.
AB  - The conservation of the polychromy of the terracotta army of the first Chinese
      emperor Qin Shihuangdi represents a special problem because of the deterioration
      of the ground layer consisting of organic material. This was triggered due to it
      having spent more than 2200 years in water-saturated soil. The consolidation of
      the polychromy was achieved through polymerisation of a specially adapted
      combination of monomers.

PMID- 14661199
TI  - Czochralski's creative mistake: a milestone on the way to the Gigabit Era.
AB  - Much of the rapid change in industry, science, and society is brought about by
      the meteoric development of the microelectronics industry. Daily life is affected
      by this development; one has only to think of mobile telephones and the chips on
      modern credit cards. The raw material for microelectronics is the single crystal
      of silicon, with very high purity and almost perfect crystal structure. About 95%
      of the world's current production of silicon single crystals is achieved using
      the process that Jan Czochralski discovered in 1916. Today, single crystals of
      silicon can be grown that are up to 2 m long, 300 mm in diameter, and weigh up to
      265 kg. The use of magnetic fields has led to significant advances in crystal
      drawing technology. Intensive research and development reveals that in addition
      to the technology, which provides crystals of ever-increasing diameter, defect
      engineering, and the control of the numerous temperature-dependent reactions of
      crystal defects, are of paramount importance.

PMID- 14661200
TI  - Synthetic approaches to a molecular Borromean link: two-ring threading with
      polypyridine templates.

PMID- 14661201
TI  - The molecule-electrode interface in single-molecule transistors.

PMID- 14661202
TI  - Metal-bridged polymers as insoluble multicomponent asymmetric catalysts with high
      enantiocontrol: an approach for the immobilization of catalysts without using any
      support.

PMID- 14661203
TI  - A bowl-shaped triarylphosphane with a large cone angle: synthesis and
      crystallographic analysis of a [(PdX2)3(PR3)2]-type complex.

PMID- 14661204
TI  - Regulatory strategies in the complexation and release of a noncovalent guest
      trimer by a self-assembled molecular cage.

PMID- 14661205
TI  - [Ni6(SCH2CH2OH)12]: a double crown [12]metallacrown-6 nickel(II) cluster.

PMID- 14661206
TI  - A stable salt of the tris(ethene)silver cation: structure and characterization of
      [Ag(eta2-C2H4)3]+[Al[OC(CF3)3]4]-.

PMID- 14661207
TI  - Heterometallic cluster assembly on a rhenium-monocarborane substrate.

PMID- 14661208
TI  - Trimethylsilyl pentafluorophenylbis(trifluoromethanesulfonyl)methide as a super
      Lewis acid catalyst for the condensation of trimethylhydroquinone with isophytol.

PMID- 14661210
TI  - The palladium-catalyzed C-H activation of benzylic gem-dialkyl groups.

PMID- 14661209
TI  - A proton-fuelled DNA nanomachine.

PMID- 14661211
TI  - A nucleoside conjugate containing a metallacarborane group and its incorporation
      into a DNA oligonucleotide.

PMID- 14661213
TI  - Highly enantioselective addition of phenylacetylene to aldehydes catalyzed by a
      beta-sulfonamide alcohol-titanium complex.

PMID- 14661212
TI  - Parallel, double-helix DNA nanostructures using interstrand cross-linked
      oligonucleotides with bismaleimide linkers.

PMID- 14661214
TI  - Toward an improved understanding of the unusual reactivity of
      Pd0/trialkylphosphane catalysts in cross-couplings of alkyl electrophiles:
      quantifying the factors that determine the rate of oxidative addition.

PMID- 14661215
TI  - A strategy for generating naked-metal clusters for gas-phase reactivity studies
      by FTICR-MS.

PMID- 14661216
TI  - Fulvenes from enediynes: regioselective electrophilic domino and tandem
      cyclizations of enynes and oligoynes.

PMID- 14661217
TI  - Styrene synthesis: high conversion over unpromoted iron oxide catalysts under
      practical working conditions.

PMID- 14661218
TI  - Enantioselective, copper(I)-catalyzed three-component reaction for the
      preparation of propargylamines.

PMID- 14661219
TI  - Oligofunctional DNA-gold nanoparticle conjugates.

PMID- 14661221
TI  - Capillary electrophoresis-mass spectrometry: 15 years of developments and
      applications.
AB  - Since its introduction in 1987, capillary electrophoresis-mass spectrometry (CE
      MS) has developed to a well accepted multidimensional analytical approach
      complementary and/or competitive to classical MS-hyphenated separation
      techniques. The threefold combination of rapid developments of an exceptional
      separation technique, of selective mass detection possibilities, and of very mild
      ionization modes first allowed these progresses. This article shows the CE
      specificities that need to be well controlled/known, compared to classical and
      more routinely used liquid chromatography in the light of its coupling to MS. The
      major trends and developments over the last 15 years and most of the reviews and
      applications found in ISI Web of science and publisher databases are presented in
      a tabulated way. The reader can thus rapidly find existing CE-MS analysis
      techniques in his field of research and application (forensics, environment,
      bioanalytics, pharmaceutics, and metabolites).

PMID- 14661222
TI  - Advances in capillary electrophoretically mediated microanalysis.
AB  - Recent developments in the use of capillary electrophoretic techniques for the in
      line study of enzyme reactions and derivatization protocols are reviewed. The
      article is divided into two parts: (i) in-line enzyme reactions and (ii) in-line
      derivatization. The first part introduces electrophoretically mediated
      microanalysis (EMMA) and discusses and illustrates the different modes of EMMA. A
      literature overview is provided, starting from 1996, and the investigated enzymes
      are classified into two tables based on the mode of engagement (i.e., continuous
      or transient) of the developed EMMA-based assay. The second part starts with an
      introduction of the procedures and the nomenclature used in the area of in-line
      derivatization protocols based on EMMA. Reported derivatization procedures are
      discussed and classified in tables, according to the functional group that is
      derivatized.

PMID- 14661223
TI  - Applications of affinity interactions in capillary electrophoresis.
AB  - Capillary electrophoresis (CE) has proven useful for the study of reversible
      molecular interactions. This is because highly efficient and reproducible
      separations take place in an environment where molecular interactions may
      contribute to selectivity without being inhibited by adverse buffer conditions.
      Affinity CE may be used to estimate quantitative binding data (binding constants
      and in some cases binding stoichiometries and rate constants) for various
      molecular interactions. Specific binding interactions (e.g., based on antibodies
      or aptamers) may also be utilized to quantitatively measure specific analytes
      using CE. Applications within these areas are here reviewed with focus on the
      last three years and with emphasis on novel concepts as well as innovative
      methodology and technology. It is concluded that the affinity CE approach is of
      growing versatility and will continue to play an integral role in discovering,
      characterizing, and exploiting biomolecular interactions.

PMID- 14661224
TI  - Molecularly imprinted polymers in capillary electrochromatography: recent
      developments and future trends.
AB  - The developments in molecularly imprinted polymer (MIP)-based capillary
      electrochromatography (CEC) achieved during the past years are reviewed in this
      article. The MIP is prepared using a templated polymerization reaction and
      results in a material with a high selectivity towards a predetermined target. The
      selectivity of the MIP is comparable to that of the biological antibodies,
      however, the MIP is much more stable and is thus able to withstand extremely
      harsh conditions in terms of pH, temperature, and organic solvents. The high
      selectivity and stability of the MIP made it an interesting candidate for
      application as stationary phase sorbent in chromatography. However, due to slow
      kinetics the efficiency of the early MIP columns, which were predominantly
      applied in high-performance liquid chromatography (HPLC), were limited. The use
      of CEC was thought to improve the efficiency of the MIP-based separation system.
      The small dimensions of the capillary format employed in CEC have put demands on
      the polymer systems which have resulted in the development of many different
      polymer formats. Thus, this need for novel MIP formats for applications in CEC
      has contributed a lot to the general development of MIP formats as well as to the
      knowledge in MIP synthesis and characteristics.

PMID- 14661225
TI  - Recent applications of microemulsion electrokinetic chromatography.
AB  - Microemulsions are used in a similar way as micellar solutions are used for
      separations in capillary electrophoresis. Within the last approximately six
      years, a number of papers have appeared in the literature in which the separation
      characteristics of microemulsion electrokinetic chromatography (MEEKC) have been
      investigated. The total number of papers dealing with MEEKC is now close to 100.
      One of the major fields of application for MEEKC has been the characterization of
      the lipophilicity of chemical substances but the technique has also been applied
      for the analysis of substances within the fields of natural products,
      pharmaceuticals, vitamins, peptides, proteins, and nucleic acid bases as well as
      nucleosides. An overview of the applications is given together with the
      microemulsions used for each application.

PMID- 14661226
TI  - Recent applications of capillary isoelectric focusing.
AB  - After the advent of capillary isoelectric focusing (CIEF) in the 80's several
      approaches have been developed in order to use the technique in routine analyses.
      The recent years showed an extensive increase in the applications of this
      technique employing its exceptionally high-resolution power. Methodological
      improvements, as well as hyphenation with other electrophoretic and
      chromatographic separation procedures, proved the versatility of CIEF in studies
      of clinically important proteins, recombinant product, cell lysates and other
      complex mixtures. The combination of CIEF with mass spectrometry detection is one
      of the major challenges for studying proteomics. This review collected the recent
      applications of CIEF including innovations in the experimental setup, remedies
      for the presence of salts in samples, calibration of the pH gradient, carrier
      ampholyte-free isoelectric focusing, the progress in micropreparation, two
      dimensional separations, etc.

PMID- 14661227
TI  - Analytical separations in open-tubular capillary electrochromatography.
AB  - This review represents a summary of recent progress in open-tubular capillary
      electrochromatography (OT-CEC) for chiral and achiral separations. The OT-CEC
      approach is an alternative to packed-CEC that could eliminate the problems
      associated with retaining frits and silica particles. In OT-CEC, the stationary
      phase is immobilized on the inner walls of the capillary. Preparation of the
      stationary phase is critical for OT-CEC. The preparation methods for capillary
      columns include (i) adsorption, (ii) covalent bonding and/or cross-linking, (iii)
      porous layers, (iv) chemical bonding after etching, (v) sol-gel, and (vi)
      molecular imprinting. Major developments, potential applications, technical
      difficulties and advantages associated with these wall coatings in OT-CEC are
      presented. In addition, the coupling of OT-CEC with mass spectrometry (MS) is
      briefly reviewed. Several applications of this hyphenated technique for
      analytical separations are also summarized.

PMID- 14661228
TI  - Recent applications in capillary electrochromatography.
AB  - The most recent and important applications in capillary electrochromatography
      (CEC) are summarized, covering literature published since May 2001. A selection
      of new developments in stationary phases for CEC is highlighted, and enantiomeric
      separations and chiral stationary phases are discussed. Also, CEC applications of
      biological molecules, pharmaceuticals, and applications in the field of
      industrial and environmental analysis are summarized. For this review three modes
      of CEC were taken into account, i.e., packed-column CEC, CEC using monolith
      technology, and open-tubular CEC.

PMID- 14661229
TI  - Silica-based monoliths for capillary electrochromatography: methods of
      fabrication and their applications in analytical separations.
AB  - This review article is intended to provide the reader with the recent advances
      made in the fabrication of silica-based monolithic capillary columns for use in
      capillary electrochromatography (CEC). The silica-based monoliths can be produced
      by three different approaches, namely (i) fusion of silica particles by thermal
      sintering, (ii) cross-linking/entrapping silica particles in a packed bed using
      the sol-gel process, and (iii) polymerization of silicon alkoxide precursors
      using the sol-gel process. Thus far, approach (iii) is the most widely used for
      fabricating silica monoliths. After providing a thorough description of each of
      the three approaches used for the production of silica-based monolithic capillary
      columns, the analytical separations performed by CEC on each kind of monolith are
      discussed.

PMID- 14661230
TI  - Recent progress in high-performance capillary bioseparations.
AB  - Bioanalysis is a fast growing domain with new technological developments in the
      field of mass spectrometry, separation science, and bioinformatics. The central
      role of separation prior to detection and evaluation of analytes is indisputable.
      In fact, since the decipherment of the human genome via multichannel capillary
      electrophoresis in combination with laser-induced fluorescence [1], the analysis
      of the proteome, i.e., the type and amount of all proteins expressed at a certain
      time by the genome in a cell or tissue [2] became of central interest. Therefore,
      new fast and sensitive capillary liquid chromatographic, electrophoretic, and
      electrochromatographic separation techniques, suitable for high-throughput
      analysis of proteins, peptides and nucleic acids, are required.

PMID- 14661231
TI  - Capillary electrophoresis of proteins 2001-2003.
AB  - This review article with 244 references describes recent developments in
      capillary electrophoresis of proteins and covers the two years since the previous
      review (Dolnik, V. Hutterer, K. Electrophoresis 2001, 22, 4163-4178) through
      Spring 2003. It covers topics related to CE of proteins including modeling of the
      electrophoretic properties of proteins, sample pretreatment, wall coatings,
      improving selectivity, detection, special electrophoretic techniques, and
      applications.

PMID- 14661232
TI  - Recent advances in capillary electrophoresis and capillary electrochromatography
      of peptides.
AB  - An overview of the recent developments in the applications of high-performance
      capillary electromigration methods, namely zone electrophoresis,
      isotachophoresis, isoelectric focusing, affinity electrophoresis, electrokinetic
      chromatography, and electrochromatography, to analysis, preparation, and
      physicochemical characterization of peptides is presented. New approaches to the
      theoretical description and experimental verification of the electromigration
      behavior of peptides and the methodological aspects of capillary
      electroseparations of peptides, such as rational selection of separation
      conditions, sample treatment, and suppression of adsorption, are discussed, and
      new developments in individual separation modes and new designs of detection
      systems applied to peptide separations are shown. Several types of applications
      of capillary electromigration methods to peptide analysis are presented: quality
      control and purity tests, determination in biomatrices, monitoring of physical
      and chemical changes and enzymatic conversions, amino acid and sequence analysis,
      and peptide mapping. The examples of micropreparative peptide separations are
      given and capabilities of capillary electromigration techniques to provide
      important physicochemical characteristics of peptides are demonstrated.

PMID- 14661233
TI  - Recent advances in amino acid analysis by capillary electrophoresis.
AB  - Amino acids are studied extensively using capillary electrophoresis. In a
      previous article, we reviewed applications reported in the period 1999-early 2001
      (Prata, C., Bonnafous, P., Fraysse, N., Treilhou, M., Poinsot, V., Couderc, F.,
      Electrophoresis 2001, 22, 4129-4138). In this article we follow on with this
      review for the period end of 2001-beginning of 2003. We will report the
      developments of detection methods, separations of enantiomers, the new medical
      applications, and amino acids in food and plants. This review shows that CE is
      more and more important for the amino acid analysis.

PMID- 14661234
TI  - Recent advances in enantioseparations of peptides by capillary electrophoresis.
AB  - The present review summarizes peptide enantioseparations by capillary
      electrophoresis with the focus on recent developments. These include the
      application of new chiral selectors and systematic studies involving series of di
      and tripeptides with either common features or with a variety of structures. One
      section emphasizes mechanistic aspects of the migration order of the enantiomers
      in cyclodextrin-assisted chiral separations with respect to the complexation
      constants and the mobilities of the transient diastereomeric complexes. In
      addition, short paragraphs on the application of chiral capillary electrophoresis
      to the determination of the stereochemical purity of peptidomimetics and on
      chiral separations of peptides by capillary electrochromatography have also been
      included.

PMID- 14661235
TI  - Recent advances in the determination of enantiomeric drugs and their metabolites
      in biological fluids by capillary electrophoresis-mediated microanalysis.
AB  - This review summarizes the recent developments in the application of
      electromigration techniques for the enantioselective analysis of drugs and
      metabolites in biological fluids. During the period covered by this review, it
      has been observed an increase in the use of negatively charged chiral selectors,
      particularly sulfobutyl ether-beta-cyclodextrin and sulfated-beta-cyclodextrin,
      and the combination of two different chiral selectors in the running buffer to
      obtain the resolution of drugs and their metabolites. Low detection limits as
      required for pharmacokinetic studies were obtained by using concentration
      techniques, including sample stacking procedures, and more sensitive detection
      systems, such as laser-induced fluorescence and mass spectrometry. Finally, the
      major points are discussed that can be considered to obtain reliable methods for
      enantioselective bioanalysis.

PMID- 14661236
TI  - Recent advances in the application of capillary electrophoresis for food
      analysis.
AB  - This article reviews recent developments in the application of capillary
      electrophoresis (CE) for the analysis of foods and food components. CE has been
      applied to a number of important areas of food analysis and is fast becoming an
      established technique within food analytical and research laboratories. Papers
      are reviewed that were published during the two years to date following the
      previous review (Electrophoresis 2001, 22, 4197-4206).

PMID- 14661237
TI  - Recent progress in pharmacokinetic applications of capillary electrophoresis.
AB  - This review is a continuation of the previous reviews (Electrophoresis 1999, 20,
      3259-3268; Electrophoresis 2001, 22, 4244-4248) to update the recent publications
      from 2001 to 2003 on pharmacokinetic studies using capillary electrophoresis
      (CE). During this period of time, CE remains as a unique analytical method for
      some studies, which would otherwise be limited by many factors, such as the
      sample volume, detection sensitivity, or separation power. It is particularly
      noticeable that the separation of chiral drugs in biological sample and the use
      of solid-phase extraction (SPE) as a simple and convenient means of sample
      preparation appear to become popular for CE-based assays. The use of CE for
      assessing complete pharmacokinetic information, however, did not show a
      significant growth during this period of time. In order to provide a broad range
      of view on how biological samples are analyzed by CE, this review will cover
      publications during the past two years on the use of CE for the analysis of drugs
      in biological fluids for general pharmacokinetic applications including drug
      monitoring and bioavailability studies.

PMID- 14661238
TI  - Analysis of antibiotics by capillary electrophoresis.
AB  - Recent developments in the characterization of antibiotics are reviewed. Many
      capillary electrophoretic techniques have been utilized in their analyses,
      addressing various aspects of quantifying, profiling, and monitoring. Laser
      induced fluorescence detection systems demonstrated their usefulness in clinical
      settings and in the monitoring of residue levels in food matrices. Different
      sample introduction methods have been explored, enhancing detection sensitivity,
      or reducing or eliminating sample manipulation prior to injection.

PMID- 14661239
TI  - Recent advances in capillary electrophoresis and capillary electrochromatography
      of pollutants.
AB  - Recent advances in capillary electrophoresis (CE) and capillary
      electrochromatography (CEC) separation, detection and sample preparation
      methodologies applied for the determination of a variety of pollutants is
      overviewed. The reviewed literature illustrates the wide range of CE
      applications, indicating the continuing interest in CE and CEC in the
      environmental field.

PMID- 14661243
TI  - The effect of phosphorylcholine-coated materials on the inflammatory response and
      fibrous capsule formation: in vitro and in vivo observations.
AB  - Several experiments were performed to compare the in vitro adhesion of human
      macrophage and granulocyte inflammatory cells to polyethylene terephthalate
      substrate and the same coated with a phosphorylcholine (PC)-based polymer. The
      inclusion of various types of serum at different stages in the assay indicated
      that protein adsorption and passivation of the surface may be responsible for
      reducing the number of inflammatory cells adhering to the uncoated polyethylene
      terephthalate controls. In all of the assays performed there was a statistically
      significant reduction (p < 0.05; analysis of variance) of the number of
      inflammatory cells adhering to the PC-coated samples, linked to the ability of
      these surfaces to resist protein adhesion. Implantations of PC-coated stainless
      steel and high-density polyethylene USP control samples were made in a rabbit
      intramuscular model. Histological examination of the number of inflammatory cells
      present around the implant sites 4 weeks postimplantation showed there were 40%
      less cells associated with the PC-coated samples compared with control, but this
      was not statistically significant. Fibrous capsule thickness, however, whereas
      marginally less at 4 weeks, had almost completely regressed for the PC-coated
      sample at 13 weeks postimplantation and was statistically thinner (p < 0.01; Mann
      Whitney U test) than the high-density polyethylene USP control. These findings
      support the view that low biointeractions observed for PC-based technology in
      vitro can result in reduced inflammation and foreign body reaction in vivo.

PMID- 14661244
TI  - Neovascularization of poly(ether ester) block-copolymer scaffolds in vivo: long
      term investigations using intravital fluorescent microscopy.
AB  - Poly(ether ester) block-copolymer scaffolds of different pore size were implanted
      into the dorsal skinfold chamber of balb/c mice. Using intravital fluorescent
      microscopy, the temporal course of neovascularization into these scaffolds was
      quantitatively analyzed. Three scaffold groups (diameter, 5 mm; 220-260
      thickness, microm; n = 30) were implanted. Different pore sizes were evaluated:
      small (20-75 microm), medium (75-212 microm) and large pores (250-300 microm).
      Measurements were performed on days 8, 12, 16, and 20 in the surrounding normal
      tissue, in the border zone, and in the center of the scaffold. Standard
      microcirculatory parameters were assessed (plasma leakage, vessel diameter, red
      blood cell velocity, and functional vessel density). The large-pored scaffolds
      showed significantly higher functional vessel density in the border zone and in
      the center (days 8 and 12) compared with the scaffold with the small and medium
      sized pores. These data correlated with a larger vessel diameter and a higher red
      blood cell velocity in the large-pored scaffold group. Interestingly, during the
      evaluation period the microcirculatory parameters on the edge of the scaffolds
      returned to values similar to those found in the surrounding tissue. In the
      center of the scaffold, however, neovascularization was still active 20 days
      after implantation. Plasma leakage and vessel diameter were higher in the center
      of the scaffold. Red blood cell velocity and functional vessel density were 50%
      lower than in the surrounding tissue. In conclusion, the dorsal skinfold chamber
      model in mice allows long-term study of blood vessel growth and remodeling in
      porous biomedical materials. The rate of vessel ingrowth into poly(ether ester)
      block-copolymer scaffolds is influenced by pore size and was highest in the
      scaffold with the largest pores. The data generated with this model contribute to
      knowledge about the development of functional vessels and tissue ingrowth into
      biomaterials.

PMID- 14661245
TI  - Collagen-hydroxyapatite composite prepared by biomimetic process.
AB  - A novel bone graft substitute comprising a porous, collagenous scaffold was
      biomimetically coated with hydroxyapatite using a simulated body fluid solution
      chemistry method. The scaffold had a porosity of approximately 85%, with pore
      sizes between 30 microm and 100 microm. Glutaraldehyde vapor was used to
      stabilize the collagenous scaffold, giving a significantly increased thermal
      stability over an unstabilized scaffold, as shown by differential scanning
      calorimetry. A thin layer (<10 microm) of crystalline hydroxyapatite was
      deposited onto the stabilized collagenous scaffold by soaking the collagenous
      construct in simulated body fluid in the presence of calcium silicate glass. The
      presence of crystalline hydroxyapatite was confirmed by X-ray diffraction, energy
      dispersive X-ray spectroscopy, and scanning electron microscopy. In vitro
      cytotoxicity testing of the composite construct using L-929 fibroblasts (ISO
      10993-5) and rabbit periosteal cells revealed a cytocompatible material that
      supported cellular attachment and proliferation.

PMID- 14661246
TI  - Photocrosslinkable polysaccharides based on chondroitin sulfate.
AB  - Photopolymerizing hydrogels have demonstrated potential for use as a scaffold in
      numerous tissue-engineering applications. The majority of photopolymerizing
      hydrogels are made from purely synthetic polymers. The purpose of this study was
      to synthesize and characterize photopolymerizing hydrogels derived from the
      biopolymer chondroitin sulfate in order to enhance the bioactivity of the
      scaffold and potentially improve tissue regeneration. Methacrylate groups were
      added to chondroitin sulfate, a major component of cartilage, using glycidyl
      methacrylate. The gels exhibited viscoelastic behavior typical of hydrogels.
      Cogels based on chondroitin sulfate and poly(ethylene glycol) demonstrated
      increasing pore size with increasing concentration of chondroitin sulfate as
      determined by water content, mechanical strength, and morphology using scanning
      electron microscopy. The chondroitin sulfate hydrogels degraded specifically in
      the presence of the enzyme chondroitinase. Chondrocytes remained viable after
      photoencapsulation and incubation in the biogels, suggesting their possible use
      for cartilage tissue engineering.

PMID- 14661247
TI  - Peripheral blood cell separation through surface-modified polyurethane membranes.
AB  - Cell separation from peripheral blood was investigated using surface-modified
      polyurethane (PU) membranes with different functional groups. Both red blood
      cells and platelets could pass through unmodified PU and PU-SO(3)H membranes,
      whereas the red blood cells preferentially passed through PU-N(C(2)H(5))(2) and
      PU-NHC(2)H(4)OH membranes. The permeation ratio of T and B cells was <25% for the
      surface-modified and unmodified PU membranes. CD34(+) cells have been recognized
      as various kinds of stem cells including hematopoietic and mesenchymal stem
      cells. The adhesiveness of CD34(+) cells on the PU membranes was found to be
      higher than that of red blood cells, platelets, T cells, or B cells. Overall, the
      adhesiveness of blood cells on the PU membranes increased in the following order:
      red blood cells </= platelets < T cells </= B cells < CD34(+) cells. Treatment of
      PU-COOH membranes with a human albumin solution to detach adhered blood cells,
      allowed recovery of mainly CD34(+) cells in the permeate, whereas both red blood
      cells and platelets could be isolated in the permeate using unmodified PU
      membranes. The PU membranes showed different permeation and recovery ratios of
      specific cells depending on the functional groups attached to the membranes.

PMID- 14661248
TI  - In vitro degradation and biocompatibility of poly(DL-lactide-epsilon
      caprolactone) nerve guides.
AB  - Bridging nerve gaps by means of autologous nerve grafts involves donor nerve
      graft harvesting. Recent studies have focused on the use of alternative methods,
      and one of these is the use of biodegradable nerve guides. After serving their
      function, nerve guides should degrade to avoid a chronic foreign body reaction.
      The in vitro degradation, in vitro cytotoxicity, hemocompatibility, and short
      term in vivo foreign body reaction of poly((65)/(35) ((85)/(15) (L)/(D)) lactide
      epsilon-caprolactone) nerve guides was studied. The in vitro degradation
      characteristics of poly(DLLA-epsilon-CL) nerve guides were monitored at 2-week
      time intervals during a period of 22 weeks. Weight loss, degree of swelling of
      the tube wall, mechanical strength, thermal properties, and the intrinsic
      viscosity of the nerve guides were determined. Cytotoxicity was studied by
      measuring the cell proliferation inhibition index (CPII) on mouse fibroblasts in
      vitro. Cell growth was evaluated by cell counting, while morphology was assessed
      by light microscopy. Hemocompatibility was evaluated using a thrombin generation
      assay and a complement convertase assay. The foreign body reaction against
      poly(DLLA-epsilon-CL) nerve guides was investigated by examining toluidine blue
      stained sections. The in vitro degradation data showed that poly(DLLA-epsilon-CL)
      nerve guides do not swell, maintain their mechanical strength and flexibility for
      a period of about 8-10 weeks, and start to lose mass after about 10 weeks.
      Poly(DLLA-epsilon-CL) nerve guides were classified as noncytotoxic, as
      cytotoxicity tests demonstrated that cell morphology was not affected (CPII 0%).
      The thrombin generation assay and complement convertase assay indicated that the
      material is highly hemocompatible. The foreign body reaction against the
      biomaterial was mild with a light priming of the immunesystem. The results
      presented in this study demonstrate that poly((65)/(35) ((85)/(15) (L)/(D))
      lactide-epsilon-caprolactone) nerve guides are biocompatible, and show good in
      vitro degradation characteristics, making these biodegradable nerve guides
      promising candidates for bridging peripheral nerve defects up to several
      centimeters.

PMID- 14661249
TI  - Assessment of wear in extensively irradiated UHMWPE cups in simulator studies.
AB  - Higher levels of UHMWPE crosslinking currently are being advocated for improved
      wear resistance of acetabular cups. Pioneering Japanese studies, begun in 1971,
      have achieved good clinical results with UHMWPE irradiated to 1000 kGy for use
      with a cemented-cup design. The objective of our study was to use contemporary
      simulator techniques to determine the in vitro wear performance of such high-dose
      irradiated cups. Extruded UHMWPE cups were processed with 500, 1000, and 1500 kGy
      of gamma-radiation doses under vacuum, annealed, and machined to shape. The cups
      were mated with 26-mm alumina heads and run in a multidirectional simulator with
      bovine serum. Over a 6-million cycle (Mc) study, the weight loss of the
      nonirradiated control cups averaged 52.8 mg/Mc + 1.4% (wear = 57.2 mm(3)/Mc). In
      contrast, the irradiated wear cups had a consistent weight gain. Thus cups with
      irradiation of 500-1500 kGy had no detectable wear in this study. The original
      machining marks still were partially evident in the wear zones, along with some
      macrofissures in the 1000- and 1500-kGy cups. Areas adjacent to the fissures
      showed delaminating plaques of 100-300 microm in size. It also was noted that the
      wear cups systematically gained more weight than their corresponding soak
      controls. Each 200-kGy radiation gain increased the fluid sorption ratio by 10%.
      The increased fluid sorption and evidence of some surface deterioration may
      indicate that such high-dose irradiated cups are more susceptible to mechanical
      damage. This indicates that we should take care to ensure that our desire to
      reduce the wear debris to a zero amount does not result in a modified UHMWPE that
      lacks the necessary mechanical properties for contemporary metal-backed cup
      designs.

PMID- 14661250
TI  - Microstructural disassembly of calcium phosphates.
AB  - Microstructural factors may play a role in the osseointegration of calcium
      phosphates. In this paper, direct microstructural interactions between
      crystalline calcium phosphates and the biological milieu are reported.
      Degradation via exposure to osteoblast culture closely resembles in vivo
      interactions with subcutaneous tissues in a bovine model at early time periods.
      That these interactions were common to both experiments constitutes one of the
      few known examples of in vitro-in vivo correspondence. Interestingly, the
      degradation of phase pure hydroxyapatite (HA) in vitro was more rapid than that
      of biphasic HA in vivo. In both cases, grain extraction/pullout was frequently
      observed. This suggests a connection to smaller-scale observations of epitaxial
      CHA nucleation and growth on pre-existing HA grains. A microstructure in which
      the grain boundary is dissolving/corroding can apparently be disassembled by
      forces transmitted through biological structures. These observations are distinct
      from those of simple non-biological solutions and prove that biological
      environments can interact with the material beneath the ceramic-cell/ceramic
      tissue interface. Many often ignored microstructural factors-grain size, shape,
      grain boundary strength and the presence of impurity phases-may in fact control
      degradation. We also suggest that even relatively modest initial grain sizes
      will, in combination with the mild/absent foreign body response to calcium
      phosphates, result in lengthy in vivo particle resistence.

PMID- 14661251
TI  - Ultrasound degradation of novel polymer contrast agents.
AB  - This report describes an investigation into factors affecting the degradation of
      novel poly(lactic-co-glycolic acid) (PLGA) contrast agents. Contrast agents
      fabricated by two different methods and varying in acoustic properties were
      compared. The effect of ultrasound frequency (5 and 10 MHz) on degradation of the
      microcapsules was also studied. High-performance liquid chromatography was used
      to quantify the production of lactic and glycolic acid to monitor agent
      degradation. The degradation pattern from the microcapsules was found to be
      closely related to capsule morphology; the more acoustically efficient capsules
      (maximum enhancement of 25 dB at 5 MHz with 0.004 mg/mL) degraded at a faster
      rate than those with lower acoustical efficiency (maximum enhancement of 25 dB at
      5 MHz only achieved with 0.6 mg/mL). The capsules also degraded fastest when
      insonated at the frequency at which they gave highest backscatter. In addition,
      despite the use of a 50:50 PLGA copolymer, more glycolic than lactic acid was
      released at early time points, which reflects the greater hydrophilicity of the
      glycolic acid residues, and greater degradation rate of glycolic acid repeat
      units. The results from this study provided unique insight into the degradation
      behavior of hollow PLGA microcapsules, and their potential in ultrasound
      diagnosis and therapy.

PMID- 14661252
TI  - Novel bioactive and biodegradable glass ceramics with high mechanical strength in
      the CaO--SiO2--B2O3 system.
AB  - Novel bioactive and biodegradable glass ceramics with high mechanical strength in
      the (50-x/2)CaO. SiO(2)--xB(2)O(3) (4.2 < or = x < or = 17.2) system were
      investigated. The systems consisted of three phases: monoclinic wollastonite,
      calcium metaborate, and amorphous borosilicate matrix. The glass ceramics
      containing 4.2 mol% and 8.4 mol% B(2)O(3) showed high bulk density and a dense
      microstructure. Mechanical strengths of the glass ceramics were higher than those
      of other bioactive ceramics: high compressive strength (2813 MPa), bending
      strength of 212 MPa, and fracture toughness of 3.12 MPa. m(1/2). The glass
      ceramic formed apatite layer on their surface in the simulated body fluid and
      showed significant biodegradation. The degree of apatite formation in the glass
      ceramics depended on the calcium metaborate content and borosilicate glassy
      matrix. Additional calcium metaborate and borosilicate glassy matrix increased
      the apatite formation rate on the surface. It might be likely that calcium
      metaborate causes supersaturation of Ca ions, for its high solubility in SBF and
      the water-reactive borosilicate glassy matrix formed Sibond;OH groups on the
      surface to provide nucleation sites for apatite formation. Also, through in vitro
      test for the biocompatibility of the CaO--SiO(2)--B(2)O(3) glass ceramics, no
      cytotoxicity of the glass ceramics were found. The results on bioactivity and
      noncytotoxicity indicated that glass ceramics in the (50-x/2)CaO. SiO(2)-
      xB(2)O(3) (4.2 < or = x < or = 17.2) system could be useful as a biodegradable
      bone replacement material.

PMID- 14661253
TI  - Numerical osteobonding evaluation of electrically polarized hydroxyapatite
      ceramics.
AB  - Enhanced osteobonding abilities of electrical polarized hydroxyapatite (HA)
      ceramics were statistically evaluated by a bone morphometric technique. HA
      ceramics with an average charge of 3.9 microCcm(-2) were implanted in tibial and
      femoral diaphyses of New Zealand white rabbits. Estimation of the affinity index,
      defined as the ratio of the direct bonding length to the HA ceramic length,
      significantly showed more active osteobonding ability with a negatively charged
      surface than with a positively charged surface and a nonpolarized HA 1 week after
      administration. The enhanced osteobonding ability attributed to the stimulated
      osteoids in the vicinity of the positively charged surface ranked above the
      nonpolarized surface. Although amounts of the newly formed bone on the HA
      surfaces increased with implantation period in all of the observation areas, the
      negatively charged surface was almost covered with bone and had the best index
      value of 94.0% at 4 weeks. The superior osteobonding activity of the negatively
      charged surfaces was statistically proven.

PMID- 14661254
TI  - Attachment of hyaluronan to metallic surfaces.
AB  - Metal implants are in general not compatible with the tissues of the human body,
      and in particular, blood exhibits a severe hemostatic response. Herein we present
      results of a technique to mask the surface of metals with a natural biopolymer,
      hyaluronan (HA). HA has minimal adverse interactions with blood and other
      tissues, but attachment of bioactive peptides can promote specific biological
      interactions. In this study, stainless steel was cleaned and then surface
      modified by covalent attachment of an epoxy silane. The epoxy was subsequently
      converted to an aldehyde functional group and reacted with hyaluronan through an
      adipic dihydrazide linkage, thus covalently immobilizing the HA onto the steel
      surface. Fluorescent labeling of the HA showed that the surface had a fairly
      uniform covering of HA. When human platelet rich plasma was placed on the HA
      coated surface, there was no observable adhesion of platelets. HA derivatized
      with a peptide containing the RGD peptide sequence was also bound to the
      stainless steel. The RGD-containing peptide was bioactive as exemplified by the
      attachment and spreading of platelets on this surface. Furthermore, when the RGD
      peptide was replaced with the nonsense RDG sequence, minimal adhesion of
      platelets was observed. This type of controlled biological activity on a metal
      surface has potential for modulating cell growth and cellular interactions with
      metallic implants, such as vascular stents, orthopedic implants, heart valve
      cages, and more.

PMID- 14661255
TI  - Numerical failure analysis of glass-fiber-reinforced composites.
AB  - The purpose of this work was to propose a new numerical model for glass-fiber
      reinforced composites. The proposed numerical model was constructed with
      orthotropic shell, isotropic shell, and beam elements representing glass fiber
      cloth, silica filler, and the remaining matrix resin, respectively. The proposed
      model was applied to failure analysis under three-point bending conditions. The
      validity of the numerical model was checked through comparisons with experimental
      results. Four types of specimens were used: composite resin, and composite resin
      with neutral, upper, and lower glass-fiber cloth reinforcement insertions. For
      all types, close agreement between the analytical and experimental results was
      confirmed. This indicates that the proposed numerical model is effective for
      evaluating the mechanical behaviors of glass-fiber-reinforced composites.

PMID- 14661256
TI  - Matrix metalloproteinases MMP-2, -9 and tissue inhibitors TIMP-1, -2 expression
      and secretion by primary human osteoblast cells in response to titanium,
      zirconia, and alumina ceramics.
AB  - Osteogenic properties of bone cells are a key parameter governing
      osseointegration of implant devices. In this context, osteoblasts have a central
      role via extracellular matrix synthesis and remodeling that they regulate through
      different protease activity. In this study, we have analyzed the expression of
      two matrix metalloproteinases (MMPs): MMP-2 (72 kDa) and MMP-9 (92 kDa) and their
      specific tissue inhibitors TIMP-1 and TIMP-2 in primary human osteoblastic cells.
      The effect of titanium, zirconia, and alumina ceramics on the synthesis of these
      proteases was assessed using reverse transcriptase-polymerase chain reaction,
      enzyme-linked immunosorbent assay, and zymographic analysis. Our results showed
      that osteoblasts express MMP-2 and -9 mRNA. Furthermore, MMP-2 mRNA expression
      was decreased by titanium and increased by alumina whereas zirconia did not have
      any significant effect. Conversely, MMP-9 mRNA expression was stimulated by
      titanium but decreased with zirconia, whereas alumina induced no significant
      changes. Zymographic analysis has evidenced pro-MMP-2 gelatinolytic activity in
      all cell populations with time-dependent increase profile; pro-MMP-9, however,
      was not detected. Enzyme-linked immunosorbent assay data confirmed the production
      of MMP-2 and very low levels of MMP-9. In addition, TIMP-1 was secreted in 24-h
      cultured cells and increased to maximal level at 48-72 h whereas TIMP-2 levels
      were very low. The interactions between human osteoblasts and the studied
      biomaterials altered both MMP-2, -9 and TIMP-1expression indicating that
      biomaterials may influence osseointegration and bone remodeling.

PMID- 14661257
TI  - Design and fabrication of standardized hydroxyapatite scaffolds with a defined
      macro-architecture by rapid prototyping for bone-tissue-engineering research.
AB  - This investigation describes the production and characterization of calcium
      phosphate scaffolds with defined and reproducible porous macro-architectures and
      their preliminary in vitro and in vivo bone-tissue-engineered response. Fugitive
      wax molds were designed and produced using a rapid prototyping technique. An
      aqueous hydroxyapatite slurry was cast in these molds. After sintering at 1250
      degrees C and then cleaning, dimensional and material characterizations of the
      scaffolds were performed. The resulting scaffolds represented the design, and
      their dimensions were remarkably consistent. A texture inherent to the layer-by
      layer production of the mold was impressed onto the vertical surfaces of the
      scaffolds. The surface roughness (R(a)) of the textured surfaces was
      significantly greater than that of the nontextured surfaces. Material analyses
      revealed a beta-TCP phase in addition to hydroxyapatite for the molded ceramics.
      Non-molded control ceramics exhibited only hydroxyapatite. Thirty scaffolds were
      seeded with culture-expanded goat bone-marrow stromal cells (BMSCs) and implanted
      subcutaneously in nude mice for 4 or 6 weeks. Histology revealed mineralized bone
      formation in all the scaffolds for both implantation periods. After 4 weeks, bone
      was present primarily as a layer on scaffold surfaces. After 6 weeks, the surface
      bone formation was accompanied by bone budding from the surface and occasional
      bridging of pores. This budding and bridging bone formation almost always was
      associated with textured scaffold surfaces. However, the area percentage of bone
      in pores was similar for the 4- and 6-week implantation periods.

PMID- 14661258
TI  - Ultrastructural comparison of hydroxyapatite and silicon-substituted
      hydroxyapatite for biomedical applications.
AB  - Silicon-substituted hydroxyapatite (Si-HA) has been shown to lead to
      significantly increased rates of bone apposition when compared with phase-pure
      hydroxyapatite (HA) bioceramic implants (Patel N, et al. J Mater Sci Mater Med
      2002;13:1199-1206). However, uncertainty remains about the mechanism by which Si
      increases the in vivo bioactivity. In this study, defect structures in Si-HA were
      observed and characterized for the first time using high-resolution transmission
      electron microscopy. Using tilting experiments and the g. b = 0 criterion for
      invisibility, the Burgers vectors of dislocations in phase-pure HA and 0.8 wt %
      Si-HA were characterized to be screw and mixed in character. Dislocations were
      observed in both pure HA and 0.8 wt % Si-HA with no significant difference in
      dislocation density between HA and Si-HA. However, our findings suggest that an
      increased number of triple junctions in Si-HA may have a significant role in
      increasing the solubility of the material and the subsequent rate at which bone
      apposes Si-HA ceramics.

PMID- 14661259
TI  - Disulfide-crosslinked hyaluronan-gelatin sponge: growth of fibrous tissue in
      vivo.
AB  - The modification of hyaluronan (HA) and gelatin using dithiobis(propanoic
      dihydrazide) (DTP) has provided two thiolated macromolecular components of the
      extracellular matrix (ECM), specifically HA-DTPH and gelatin-DTPH. Blends of
      these thiolated ECM components were crosslinked in air to form hydrogels that
      were interpenetrating disulfide-crosslinked networks. Lyophilization of the
      hydrogels afforded sponge-like macroporous scaffolds suitable for cell attachment
      and proliferation. Increasing percentages of gelatin-DTPH (0, 25, 50, and 75%)
      were blended with HA-DTPH, and the resulting sponges were evaluated in vitro and
      in vivo as scaffolds for tissue engineering by seeding with human tracheal scar
      (HTS) fibroblasts. While cells failed to attach and grow in HA-only sponges, the
      gelatin-modified HA sponges promoted cell adhesion, proliferation, and spreading
      in vitro. Optimal attachment and growth was observed with 50% gelatin-HA sponges.
      Cell attachment to the gelatin-HA sponge could be blocked by preincubation of
      cells with a soluble fibronectin peptide Gly-Arg-Gly-Asp (GRGD). Finally, HTS
      fibroblast-seeded gelatin-HA sponges were implanted into the flanks of nude mice
      and evaluated at 2 and 8 weeks postimplantation. The sponges were fully
      biocompatible and new fibrous tissue formed, gradually replacing the sponge-like
      scaffold. The gelatin-HA sponges act as synthetic, macroporous, covalent mimics
      of the ECM and constitute novel scaffolds for cell growth and tissue
      augmentation.

PMID- 14661260
TI  - Fracture associated with hydrogen absorption of sustained tensile-loaded titanium
      in acid and neutral fluoride solutions.
AB  - The fracture of commercial pure titanium in acid and neutral fluoride solutions
      has been examined by a sustained tensile-loading test and hydrogen thermal
      desorption analysis. It was found that the fracture of titanium occurred in
      neutral 2.0% NaF solution as well as in 2.0% acidulated phosphate fluoride (APF)
      solution. The time to fracture decreased with increasing applied stress in both
      2.0% APF and 2.0% NaF solutions. In the case of the same applied stress, the time
      to fracture in the 2.0% APF solution was shorter than that in the 2.0% NaF
      solution. General corrosion was exhibited on the side surface of the tested
      specimens. The formation of sodium titanium fluoride was observed on the surface
      of the immersed specimens in the 2.0% APF solution. Hydrogen desorption of the
      tested specimen in the 2.0% APF solution was observed with a peak at
      approximately 600 degrees C. The amount of absorbed hydrogen was >300 mass ppm in
      the 2.0% APF solution under an applied stress for 24 h. The results of the
      present study imply that applying stress to titanium by immersing in fluoride
      solutions leads to the degradation of its mechanical properties.

PMID- 14661261
TI  - EDTA-induced activation of Ca-regulated proteins in the vaginal mucosa.
AB  - The effects of EDTA on the expression and topologic localization of mitogen
      activated protein (MAP) kinases (ERK, JNK, and p38), along with nitric oxide
      synthase (NOS), I-KappaB, and p53 were examined to elucidate the host response
      provoked by the intravaginal application of a female controlled drug delivery
      system (FcDDS) containing a spermicidal/microbicidal agent and EDTA.
      Immunohistochemical and immunoblotting studies were conducted to identify and
      quantitate the EDTA-inducible proteins in vaginal mucosa. The content of nitrite,
      which is one of the primary stable breakdown products of nitric oxide (NO), was
      determined to correlate the expression of NOS with NO formation in HeLa cervical
      carcinoma cell line. The immunohistochemical study demonstrated that the
      modulation of the calcium gradient by EDTA activated MAP kinases (ERK and JNK) in
      the rabbit vaginal mucosa. The results of Western immunoblot study demonstrated
      differential expression of MAP kinases (ERK and JNK) with EDTA treatment, whereas
      the expression of NOS and NF-KappaB was not affected by EDTA. There was no
      significant difference in nitrite production in the HeLa cell line upon exposure
      to EDTA compared with the control, which was consistent with the results of the
      Western blot study. The results of this work support that the regulation of MAP
      kinase was affected by calcium, which is controlled by chelation activity of
      EDTA. The specific tissue responses exerted by the loading components of a
      biomaterial-based system should be fully taken into consideration for its
      intravaginal application.

PMID- 14661262
TI  - Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic
      differentiation of marrow mesenchymal stem cells in porous hydroxyapatite
      ceramic.
AB  - To evaluate the growth/differentiation factor-5 (GDF-5) in the in vivo osteogenic
      potential of bone marrow mesenchymal stem cells (MSCs), we subcutaneously
      implanted five different kinds of hydroxyapatite (HA) ceramic implants: HA alone,
      GDF-5/HA composites (GDF/HA), MSCs/HA composites, the MSCs/HA composites
      supplemented with GDF-5 (GDF/MSCs/HA), and recombinant bone morphogenetic protein
      2 (BMP/MSCs/HA). Neither the HA alone nor the GDF/HA composites exhibited any
      bone formation at any time after implantation. At 4 weeks, the MSCs/HA composites
      exhibited a certain amount of bone formation in some pore areas. In contrast, at
      2 weeks, the GDF/MSCs/HA composites exhibited histologically obvious de novo bone
      formation together with active osteoblasts in many pore areas and additional bone
      formation at 4 weeks. In the de novo formed bone, neither chondrocytes nor
      endochondral bone was detected. The GDF/MSCs/HA composites also showed high
      alkaline phosphatase (ALP) and osteocalcin expression determined at both the
      protein and gene levels and the high level of expression was well maintained even
      at 4 weeks. Compared with GDF/MSCs/HA, the BMP/MSCs/HA composites exhibited
      excellent osteogenesis with relatively early osteoblastic phenotype expression.
      The results indicate that GDF-5 synergistically enhances de novo bone formation
      capability of MSCs/HA composite and suggest that tissue-engineered GDF/MSCs/HA
      composites could be used as bone graft substitutes.

PMID- 14661263
TI  - In vitro assessment of bioactive coatings for neural implant applications.
AB  - Recent efforts in our laboratory have focused on developing methods for
      immobilizing bioactive peptides to low cell-adhesive dextran monolayer coatings
      and promoting biospecific cell adhesion for biomaterial implant applications. In
      the current study, this dextran-based bioactive coating technology was developed
      for silicon, polyimide, and gold, the base materials utilized to fabricate our
      prototype neural implants. Chemical composition of all modified surfaces was
      verified by X-ray photoelectron spectroscopy (XPS). We observed that surface
      immobilized dextran supported very little cell adhesion in vitro (24-h incubation
      with serum-supplemented medium) on all base materials. Inactive nonadhesion
      promoting Gly-Arg-Ala-Asp-Ser-Pro peptides immobilized on dextran-coated
      materials promoted adhesion and spreading at low levels not significantly
      different from dextran-coated substrates. Arg-Gly-Asp (RGD) peptide-grafted
      surfaces were observed to promote substantial fibroblast and glial cell adhesion
      with minimal PC12 (neuronal cell) adhesion. In contrast, dextran-coated materials
      with surface-grafted laminin-based, neurite-promoting Ile-Lys-Val-Ala-Val (IKVAV)
      peptide promoted substantial neuron cell adhesion and minimal fibroblast and
      glial cell adhesion. It was concluded that neuron-selective substrates are
      feasible using dextran-based surface chemistry strategies. The chemical surface
      modifications could be utilized to establish a stable neural tissue-implant
      interface for long-term performance of neural prosthetic devices.

PMID- 14661264
TI  - Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes.
AB  - Previous investigations have shown that both the early biological response and
      the mechanical properties of a porous hydroxyapatite bone graft substitute are
      highly sensitive to its pore structure. The objective of this study was to
      evaluate whether the pore structure continued to influence bone integration in
      the medium to long term. Two screened batches of porous hydroxyapatite (PHA)
      designated as batch A and batch B, with porosities of approximately 60 and 80%,
      respectively, were selected for this study and implanted for periods of 5, 13,
      and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric
      analysis of the absolute volume of bone ingrowth within batch A and B implants
      from 5 to 26 weeks showed that the absolute volume of bone ingrowth was
      consistently lower in batch A (10-21%), compared to batch B implants (24-31%).
      However, when the volume of bone ingrowth was normalised for the available pore
      space, this difference was reduced (23-47% and 32-42% for batches A and B,
      respectively). These observations suggest that differences in the volume of bone
      ingrowth initially depended on pore interconnectivity rather than pore size,
      whereas the volume or morphology of the PHA influenced the volume and morphology
      of bone ingrowth at later time points. Compression testing showed that bone
      ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a
      strong correlation was identified between mechanical properties and the absolute
      volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks,
      there was no significant variation in the ultimate compressive strength of
      integrated batch A and B implants. This similarity in ultimate mechanical
      properties indicated that the absolute volume of ingrowth may be mediated by the
      PHA structure through its impact on the dynamics of the local biomechanical
      environment. The results of push-out testing showed that fixation of PHA bone
      graft substitutes was independent of density within the range studied, with no
      significant difference in the interfacial shear stress between batches A and B at
      each time point throughout the study.

PMID- 14661267
TI  - Prion diseases: from molecular biology to intervention strategies.
AB  - Prion diseases are fatal neurodegenerative infectious disorders for which no
      therapeutic or prophylactic regimens exist. Understanding the molecular process
      of conformational conversion of the cellular prion protein (PrP(c)) into its
      pathological isoform (PrP(Sc)) will be necessary to devise effective antiprion
      strategies. In recent years, new findings in the cell biology of PrP(c), in the
      molecular pathogenesis of PrP(Sc), and in the cellular quality control mechanisms
      involved in these scenarios have accumulated. A function of the prion protein in
      signalling, the possible impact of the proteasome, and aggresomes as
      intracellular waste deposits have been described. Here, important pathogenetic
      similarities with the more frequent neurodegenerative disorders are evident. The
      need for therapeutic, postexposure, and prophylactic possibilities was
      drastically illustrated by the emergence of variant Creutzfeldt-Jakob disease
      (vCJD), a new human prion disease caused by bovine spongiform encephalopathy
      (BSE) derived prions. Although prion infectivity in humans is usually restricted
      to the central nervous system, in vCJD patients prions are present in the lympho
      reticular system, posing a theoretical risk of accidental human-to-human
      transmission. A variety of chemical antiprion substances have been reported in in
      vitro and cell culture based assays or in animal studies. Occasionally, they have
      also made their way into the first human trials. In addition, various promising
      interference strategies have been devised in transgenic models, although they are
      usually hard to transfer into nontransgenic in vivo situations. New findings in
      the fields of peripheral prion pathogenesis and immune system involvement fuelled
      the search for antiprion strategies formerly considered to be entirely
      impossible. This opened the door towards classical immunological interference
      techniques. Remarkably, passive and even active vaccination approaches now seem
      to be realistic goals.

PMID- 14661268
TI  - Structural aspects of adhesion to and invasion of host cells by the human
      pathogen Listeria monocytogenes.

PMID- 14661269
TI  - Looking at molecules-an essay on art and science.

PMID- 14661270
TI  - A "Holey" supramolecular approach to the detection of enzyme activity.

PMID- 14661271
TI  - Sticky proteins for stem cells.

PMID- 14661272
TI  - Chemoenzymatic synthesis of branched oligo- and polysaccharides as potential
      substrates for starch active enzymes.
AB  - Oligo- and polysaccharides embodying the alpha-maltotriosyl-6(II)-maltotetraosyl
      structure were readily synthesized by transglycosylation of maltosyl fluoride
      onto panose and pullulan catalysed by the bacterial transglycosylase cyclodextrin
      glycosyltransferase (CGTase). The two products obtained proved useful for
      increasing the knowledge of substrate binding and processing at the active site
      of barley limit dextrinase that is involved in the metabolism of amylopectin by
      acting upon its branch points.

PMID- 14661273
TI  - Intracellular delivery of bioactive peptides to RBL-2H3 cells induces beta
      hexosaminidase secretion and phospholipase D activation.
AB  - This investigation compared the secretory efficacies of a series of peptides
      delivered to the cytoplasm of RBL-2H3 mast cells. Mimetic peptides, designed to
      target intracellular proteins that regulate cell signalling and membrane fusion,
      were synthesised as transportan 10 (TP10) chimeras for efficient plasma membrane
      translocation. Exocytosis of beta-hexosaminidase, a secretory lysosomal marker,
      indicated that peptides presenting sequences derived from protein kinase C (PKC;
      C1 H-CRRLSVEIWDWDL-NH(2)) and the CB(1) cannabinoid receptor (C3 H
      RSKDLRHAFRSMFPSCE-NH(2)) induced beta-hexosaminidase secretion. Other peptide
      cargoes, including a Rab3A-derived sequence and a homologue of C3, were inactive
      in similar assays. Translocated C1 also activated phospholipase D (PLD), an
      enzyme intimately involved in the regulated secretory response of RBL-2H3 cells,
      but C1-induced secretion was not dependent upon phosphatidate synthesis. Neither
      down-regulation of Ca(2+)-sensitive isoforms of PKC nor the application of a
      selective PKC inhibitor attenuated the secretory efficacy of C1. These
      observations indicate that the molecular target of C1 is a protein involved in
      the regulated secretory pathway that is upstream of PLD but is not a PKC isoform.
      This study also confirmed that TP10 is a relatively inert cell-penetrating vector
      and is, therefore, widely suitable for studies in cells that are sensitive to
      peptidyl secretagogues.

PMID- 14661275
TI  - DNA mismatch-specific base flipping by a bisacridine macrocycle.
AB  - Most, if not all, enzymes that chemically modify nucleobases in DNA flip their
      target base from the inside of the double helix into an extrahelical position.
      This energetically unfavorable conformation is partly stabilized by specific
      binding of the apparent abasic site being formed. Thus, DNA base-flipping
      enzymes, like DNA methyltransferases and DNA glycosylases, generally bind very
      strongly to DNA containing abasic sites or abasic-site analogues. The macrocyclic
      bisacridine BisA has previously been shown to bind abasic sites. Herein we
      demonstrate that it is able to specifically recognize DNA base mismatches and
      most likely induces base flipping. Specific binding of BisA to DNA mismatches was
      studied by thermal denaturation experiments by using short duplex
      oligodeoxynucleotides containing central TT, TC, or TG mismatches or a TA match.
      In the presence of the macrocycle a strong increase in the melting temperature of
      up to 7.1 degrees C was observed for the mismatch-containing duplexes, whereas
      the melting temperature of the fully matched duplex was unaffected. Furthermore,
      BisA binding induced an enhanced reactivity of the mispaired thymine residue in
      the DNA toward potassium permanganate oxidation. A comparable reactivity has
      previously been observed for a TT target base mismatch in the presence of DNA
      methyltransferase M.TaqI. This similarity to a known base-flipping enzyme
      suggests that insertion of BisA into the DNA helix displaces the mispaired
      thymine residue into an extrahelical position, where it should be more prone to
      chemical oxidation. Thus, DNA base flipping does not appear to be limited to DNA
      modifying enzymes but it is likely to also be induced by a small synthetic
      molecule binding to a thermodynamically weakened site in DNA.

PMID- 14661274
TI  - Adhesion inhibition of F1C-fimbriated Escherichia coli and Pseudomonas aeruginosa
      PAK and PAO by multivalent carbohydrate ligands.
AB  - In order to evaluate their inhibition of bacterial adhesion, the carbohydrate
      sequences GalNAcbeta1-->4Gal and GalNAcbeta1-->4Galbeta1-->4Glc were synthesized.
      The disaccharide was conjugated to dendrons based on the 3,5-di-(2-aminoethoxy)
      benzoic acid branching unit to yield di- and tetravalent versions of these
      compounds. A divalent compound was also prepared that had significantly longer
      spacer arms. Relevant monovalent compounds were prepared for comparison. Their
      anti-adhesion properties against F1C-fimbriated uropathogenic Escherichia coli
      were evaluated in an ELISA-type assay by using a recombinant strain and also by
      using Pseudomonas aeruginosa strains PAO and PAK. Adhesion inhibition was
      observed in all cases, and multivalency effects of up to one order of magnitude
      were observed. The combination of spacer and multivalency effects led to a 38
      fold increase in the potency of a divalent inhibitor with long spacer arms
      towards the PAO strain when compared with the free carbohydrate.

PMID- 14661276
TI  - Functionalizing nanocrystalline metal oxide electrodes with robust synthetic
      redox proteins.
AB  - De novo designed synthetic redox proteins (maquettes) are structurally simpler,
      working counterparts of natural redox proteins. The robustness and adaptability
      of the maquette protein scaffold are ideal for functionalizing electrodes. A
      positive amino acid patch has been designed into a maquette surface for strong
      electrostatic anchoring to the negatively charged surfaces of nanocrystalline,
      mesoporous TiO(2) and SnO(2) films. Such mesoporous metal oxide electrodes offer
      a major advantage over conventional planar gold electrodes by facilitating
      formation of high optical density, spectroelectrochemically active thin films
      with protein loading orders of magnitude greater (up to 8 nmol cm(-2)) than that
      achieved with gold electrodes. The films are stable for weeks, essentially all
      immobilized-protein display rapid, reversible electrochemistry. Furthermore,
      carbon monoxide ligand binding to the reduced heme group of the protein is
      maintained, can be sensed optically and reversed electrochemically. Pulsed UV
      excitation of the metal oxide results in microsecond or faster photoreduction of
      an immobilized cytochrome and millisecond reoxidation. Upon substitution of the
      heme-group Fe by Zn, the light-activated maquette injects electrons from the
      singlet excited state of the Zn protoporphyrin IX into the metal oxide conduction
      band. The kinetics of cytochrome/metal oxide interfacial electron transfer
      obtained from the electrochemical and photochemical data obtained are discussed
      in terms of the free energies of the observed reactions and the electronic
      coupling between the protein heme group and the metal oxide surface.

PMID- 14661277
TI  - Metal-chelating amino acids as building blocks for synthetic receptors sensing
      metal ions and histidine-tagged proteins.
AB  - Protein structure and function rely on a still not fully understood interplay of
      energetic and entropic constraints defined by the permutation of the twenty
      genetically encoded amino acids. Many attempts have been undertaken to design
      peptide-peptide interaction pairs and synthetic receptors de novo by using this
      limited number of building blocks. We describe a rational approach to creating a
      building block based on a tailored metal-chelating amino acid. Nepsilon,Nepsilon
      bis(carboxymethyl)-L-lysine can be flexibly introduced into peptides by 9
      fluorenylmethoxycarbonyl solid-phase chemistry. The corresponding metal-chelating
      peptides act as metal sensors and synthetic receptors for histidine-tagged
      proteins. These biochemical tweezers will open new ways to control protein
      protein interactions, to design peptide-based interaction pairs, or to generate
      switchable protein function.

PMID- 14661278
TI  - Antibiotic and hemolytic activity of a beta2/beta3 peptide capable of folding
      into a 12/10-helical secondary structure.

PMID- 14661279
TI  - Icosahedral virus particles as polyvalent carbohydrate display platforms.

PMID- 14661280
TI  - Cyclopropane fatty acid synthase from Escherichia coli: enzyme purification and
      inhibition by vinylfluorine and epoxide-containing substrate analogues.

PMID- 14661282
TI  - [IUpdating the editorial board directive].

PMID- 14661283
TI  - [Opinion: Radiology language: basic problems].
AB  - Although radiology utilizes highly sophisticated equipment, its basic tool
      remains radiology reports. Of the many problems related to the use of radiology
      language in Turkish, several are more prominent. Among these more prominent
      problems are the selective use of non-Turkish words in the presence of their
      Turkish counterparts, mistakes in the use of non-Turkish words, and improper use
      of the Turkish grammar and linguistics. The content and visual design of
      radiology reports in Turkey also need considerable improvement. In this article,
      problems in these areas are outlined and some advices regarding solutions are
      made.

PMID- 14661284
TI  - [The effect of giving information forms about side effects of intravenous
      iodinated contrast material on the anxiety level of patients].
AB  - PURPOSE: We aimed to determine the effect of informing patients about side
      effects of the contrast material on the level of patients' anxiety. MATERIALS AND
      METHODS: Two hundred-ninety seven patients undergoing computed tomography
      examination were enrolled in the study. Patients were grouped in three
      categories: (1) patients informed about adverse effects of contrast material and
      waiting for i.v. contrast material injection, (2) uninformed patients waiting for
      i.v. contrast material injection, (3) uninformed patients undergoing unenhanced
      CT examination. All patients were requested to complete a questionnaire including
      a standard anxiety test. The results were compared statistically. RESULTS: The
      mean anxiety scores calculated by variant analysis were 39.2 +/- 11.7, 42 +/-
      10.4, and 38.6 +/- 9.5 in groups 1, 2, and 3, respectively. No statistically
      significant difference was found between the anxiety scores of the 3 groups.
      CONCLUSION: Informing patients about the adverse effects of the contrast material
      does not affect their anxiety level.

PMID- 14661285
TI  - [Review: Fetal risks in radiological examinations and estimated fetal absorption
      dose].
AB  - There has been growing concern about radiation exposure in the case of pregnant
      women who undergo radiological examinations. Lack of knowledge is responsible for
      the great anxiety and probably unnecessary termination of pregnancies. The main
      effects of radiation on the human embryo and fetus are prenatal death, growth
      retardation, congenital malformations and mental retardation as well as stocastic
      effect in lower doses. Prenatal doses from most properly performed diagnostic
      procedures present no measurably increased risk of prenatal death, malformation
      or impairment of mental development over the background incidence of these
      entities. The dose received depends on mAs, but other parameters are necessary
      for calculation (film source distance, kV, filtration). To prevent accidental
      irradiation of the fetus, women must receive information about radiation effects,
      and the physician must choose a nonirradiating technique. Termination of
      pregnancy is an individual decision affected by many factors. Fetal doses below
      50 mGy should not be considered a reason for terminating pregnancy. For a low
      dose procedure such as a chest X-ray, the only information that may be needed is
      a verbal assurance that the risk is judged to be low. When fetal doses are above
      1 mGy and above, more detailed explanation is given.

PMID- 14661286
TI  - [Review: Three dimensional ultrasound].
AB  - Ultrasound is a widely used imaging modality in medical practice for the
      diagnosis and staging of diseases. In the last decade it has benefited from major
      advantages in technology, and three dimensional ultrasound has been developed.
      This new modality is rapidly achieving widespread application in numerous
      situations since it helps to overcome some limitations related with two
      dimensional imaging. The developments in high speed computer technology have
      improved volume data acquisition, imaging and storage. It is believed that volume
      ultrasound will be a routine part of the diagnosis and treatment of patients with
      the proven advantages owing to its basic working principles. In this paper we
      attempt to describe the working principles of three dimensional ultrasound,
      developments in a number of three dimensional imaging systems, reconstruction and
      viewing methods, documentation, volume measurement methods, and discuss various
      clinical applications with some examples.

PMID- 14661287
TI  - [Pictorial essay: Evaluation of intracranial lipomatous masses with MRI].
AB  - The lipid containing tumors of the intracranial region are rare and usually
      benign masses. The major lipomatous masses may be listed as lipomas, dermoid
      cysts, and the tumors with lipoid metaplasia, most common of which is lipomatous
      meningioma. MRI characteristics of these rare entities have been presented, and
      the underlying reasons for those appearances on MRI have been discussed in this
      pictorial review.

PMID- 14661288
TI  - [Pictorial essay: Pneumocephalus].
AB  - Imaging in pneumocephalus aids in the diagnosis and management of this condition,
      which usually results from trauma, iatrogenic causes, infections, tumors, and
      cranium abnormalities. The role of computed tomography and magnetic resonance
      imaging is especially addressed in this article.

PMID- 14661289
TI  - [Case report: Cerebral superficial siderosis: MRI findings].
AB  - Superficial siderosis of the central nervous system is a rare condition
      characterized by deposition of hemosiderin in the leptomeninges, subpial tissue
      and spinal cord. Magnetic resonance imaging provides prompt diagnosis of this
      entity. Three cases of cerebral superficial siderosis are presented in this
      study. On T2-weighted images, typical hypointense rims were observed under the
      brain surface. In one patient, there was also spinal superficial siderosis
      findings.

PMID- 14661290
TI  - [Temporal bone CT and MRI in cochlear implant candidates].
AB  - PURPOSE: Hearing can be restored by cochlear implantation in patients with
      sensorineural hearing loss, who have a normal seventh cranial nerve. The aim of
      imaging in cochlear implant candidates is to determine the etiology of the
      hearing loss, congenital malformations and variations that may cause difficulty
      during the operation, patency of the cochlea and the presence of the seventh,
      cranial nerve. The aim of this study is to review the literature and to discuss
      the imaging findings that may affect the type and success of the operation.
      MATERIALS AND METHODS: 33 cochlear implant candidates, who underwent high
      resolution computed tomography, were included in the study. High resolution fast
      spin echo T2 weighted and constructive interference in steady state sequences
      were performed in 23 patients with a 1.5 Tesla magnetic resonance unit. RESULTS:
      Computed tomography and magnetic resonance imaging were normal in 16 patients.
      Unilateral or bilateral labyrinthine ossification was detected in 4 patients.
      Variations of the temporal bone, congenital malformations, sequelae of chronic
      otitis and trauma were detected in 13 patients. Cochlear implantation was
      performed in 5 patients. Operative difficulty, complications and postoperative
      outcome were noted in these 5 patients. CONCLUSION: High resolution computed
      tomography and magnetic resonance images obtained by high resolution T2 weighted
      fast spin echo sequence and constructive interference in steady state sequence
      help the surgeon in planning the operation and predict potential complications in
      cochlear implant candidates.

PMID- 14661291
TI  - [HRCT findings in congenital aural atresia].
AB  - PURPOSE: To define high resolution computed tomography findings in the external,
      middle and inner ear of patients with congenital aural atresia and to emphasize
      the importance of these findings in the preoperative evaluation. MATERIALS AND
      METHODS: Twenty one patients with congenital aural atresia (14 male, 7 female)
      aged between 1-30 years were evaluated with high resolution computed tomography
      of the temporal bone. A Toshiba TCT-600 scanner was used in 11 cases, and a
      Xvision/GX scanner was used in 10 cases. Sections 1 mm thick were obtained in
      axial and coronal projections using high bone detail algorithms. Sagittal
      reformations were also made when necessary. RESULTS: Forty-two ears in 21
      patients with congenital aural atresia were studied. These included 8 patients
      with high bilateral and 13 with unilateral congenital aural atresia in which 8
      patients had right sided and 5 patients had left sided atresia. Stenosis of the
      external auditory canal was found in 11 ears, complete atresia was found in 13
      ears, incomplete atresia was found in 1 ear. There was varied ossicular deformity
      in 18 ears. Anomalies of the stapes and oval window were found in 6 ears. An
      anteriorly located mastoid segment of the facial nerve canal was identified in 11
      ears. An inferiorly located tympanic segment of the facial nerve canal was
      identified in 2 ears, and 3 ears had an abnormal posterior orientation of the
      mandibular condyles. Only 2 patients had associated inner ear deformity.
      CONCLUSION: High resolution computed tomography is an effective method for the
      evaluation of the anomalies of the external, middle and inner ear in patients
      with congenital aural atresia and for planning the surgical treatment.

PMID- 14661292
TI  - [Case report: Maxillary myxoma].
AB  - Maxillary myxoma is a rare benign mesenchymal tumor of unknown etiology. Although
      odontogenic myxomas are benign and nonmetastasizing tumors, they are locally
      invasive and have a propensity to recur if incompletely resected. We report a
      case of odontogenic myxoma involving the anterior part of the maxilla and discuss
      the role and findings of radiologic imaging.

PMID- 14661293
TI  - [Case report: Sublingual dermoid cyst].
AB  - Dermoid and epidermoid cysts are developmental lesions that occur in the head and
      neck with an incidence ranging from 1.6 to 6.9%, and they represent less than
      0.01% of all oral cavity cysts. We present a case of sublingual dermoid cyst in a
      19-year-old male with ultrasound and MRI features and review the literature.

PMID- 14661294
TI  - [Detectability of intraperitoneal free air by ultrasonography].
AB  - PURPOSE: We evaluated the role of ultrasonography in the detection of
      pneumoperitoneum. MATERIALS AND METHODS: Eleven patients who had been diagnosed
      as acute abdomen and pneumoperitoneum were evaluated by ultrasonography and
      direct radiographies. An additional ultrasonographic feature named "scissoring
      technique" was also evaluated. RESULTS: All patients had pneumoperitoneum in
      ultrasonographic and radiographic examination. The radiologic findings were
      verified with surgical results. The scissoring technique was found to be as
      accurate as other sonographic and radiographic sings. CONCLUSION: Ultrasonography
      is a sensitive technique for diagnosing pneumoperitoneum and it can be safely
      used as a first line imaging modality. If future studies confirm, the scissoring
      technique can be used in the ultrasonographic diagnosis of the pneumoperitoneum.

PMID- 14661295
TI  - [Staging of urinary bladder tumors with CT and MRI].
AB  - PURPOSE: The purpose of this study was to evaluate the performance of spiral CT
      and MRI in patients with bladder tumor. MATERIALS AND METHODS: In this study,
      patients with suspected urinary bladder tumor were evaluated by abdominal CT and
      MRI. This study included 32 patients. In 23 cases, transurethral resection (TUR),
      and in 9 cases radical cystectomy was performed. Additionally, pelvic lymph node
      dissection was performed in 9 patients. RESULTS: According to the pathological
      results of TUR-performed patients; the accuracy of spiral CT and MRI in
      preoperative staging of bladder tumors was 41.6% and 83.3%, respectively. The
      accuracy of spiral CT and MRI in preoperative staging of bladder tumors were
      66.6% and 77.7% in patients who underwent radical cystectomy. Pelvic lymph node
      involvement was evaluated properly with MRI and CT. CONCLUSION: In the
      preoperative staging of bladder tumors, MRI is superior to CT. The superiority is
      more definite especially in early stage tumors.

PMID- 14661296
TI  - [Case report: Membranous obstruction of the inferior vena cava associated with
      hepatocellular carcinoma].
AB  - The incidence of membranous obstruction of the inferior vena cava is rare, but
      the diagnosis is essential because of the association of this lesion with portal
      fibrosis and hepatocellular carcinoma. In membranous obstruction of the inferior
      vena cava, the hepatic segment of the inferior vena cava is obstructed by a
      fibromuscular membrane or replaced by a cordlike fibrous tissue. We report the
      computed tomography and ultrasound findings of a 45 year old patient with
      membranous obstruction of the inferior vena cava and hepatocellular carcinoma.

PMID- 14661297
TI  - [Case report: Inflammatory pseudotumor of the liver with target-like appearance].
AB  - Inflammatory pseudotumor of the liver, which is rarely seen, can mimic abscesses,
      metastases, peripheral cholangiocarcinomas and hepatocellular carcinomas. While
      it has no specific clinical and laboratory findings, detection of a "target-like
      appearance" in triphasic CT and MRI examination may be differentiated from other
      liver pathologies. In this report, triphasic CT and MRI findings of an
      inflammatory pseudotumor of the liver were presented.

PMID- 14661298
TI  - [Case report: Pedunculated leiomyosarcoma of the inferior vena cava].
AB  - Leiomyosarcoma of the inferior vena cava is a rare mesenchymal tumor which
      originates from the smooth muscle cells of the vascular wall. Its radiographic
      presentation varies from that of intraluminal lesions resulting in obstruction of
      the inferior vena cava to those of giant retroperitoneal masses extending to the
      surrounding perivascular tissues although still with minimal intraluminal
      protrusion. In this report, we present one such case in which a 31-year-old woman
      had complaints of severe abdominal pain, abdominal distension and vomiting.
      Computed tomography demonstrated a giant well-defined right-sided retroperitoneal
      mass extending from the subhepatic region down to the pelvis. She was operated on
      and the tumor was discovered to be attached to the wall of the inferior vena cava
      with a peduncle, a leiomyosarcoma being proven histologically. CT features of
      this rare tumor are presented in this report.

PMID- 14661299
TI  - [Case report: Tenosynovial giant cell tumor arising from the knee joint].
AB  - Giant cell tumor of the tendon sheath and synovium or pigmented villonodular
      synovitis of the tendon is a benign neoplasm, although there are rarely reported
      malignant metastatic forms. The most common location is the hand. Large joints
      such as the ankle and knee are infrequently affected. Diagnosis might be
      suspected radiologically, but the exact diagnosis has to be confirmed by
      histopathologic examination. In this study, we report MRI findings of three giant
      cell tumors of the tendon sheath.

PMID- 14661300
TI  - [Case report: 3D CT angiography in a patient with patent ductus arteriosus
      associated with Eisenmenger's syndrome].
AB  - Presentation of patent ductus arteriosus with Eisenmenger's syndrome can mimic
      primary pulmonary hypertension. The sensitivity of transthoracic echocardiography
      for the diagnosis of patent ductus arteriosus with Eisenmenger's syndrome has
      been estimated as low as 12%. Transesophageal echocardiography is superior to
      transthoracic echocardiography for the diagnosis of patent ductus arteriosus but
      has some severe complications. 3D CT angiography can be used to distinguish
      patent ductus arteriosus with Eisenmenger's syndrome from primary pulmonary
      hypertension.

PMID- 14661301
TI  - [Case report: Selective intraarterial thrombolysis of subacute superior
      mesenteric artery thromboembolism].
AB  - Acute embolic occlusion of the superior mesenteric artery is associated with a
      high mortality rate. Selective thrombolytic therapy appears to be effective in
      the treatment of mesenteric thromboembolism particularly in elderly patients with
      a high operative risk. We describe a case of subacute mesenteric artery occlusion
      in a 69-year-old man treated successfully by selective intraarterial infusion of
      urokinase two days after he became symptomatic.

PMID- 14661302
TI  - [Case report: Treatment with arterial embolization in a destroyed cervical
      pregnancy].
AB  - Cervical pregnancy is a rare form of ectopic pregnancy. It is frequently
      associated with extensive hemorrhage, which, in severe cases, may be stopped only
      by hysterectomy. We report a case of a destroyed cervical pregnancy simulating
      cervical cancer. The patient was conservatively managed with simple selective
      uterine artery embolization without methotrexate administration. Her vaginal
      bleeding ceased after embolization. No additional treatment was given. The
      patient resumed normal menstruation two months after embolization.

PMID- 14661303
TI  - [Case report: Percutaneous bowel drainage for jaundice due to afferent loop
      obstruction following pancreatoduodenectomy].
AB  - We present percutaneous biliary drainage in a patient with jaundice due to
      afferent loop obstruction following a pancreatoduodenectomy. Treatment strategy
      for this type of jaundice is discussed with a review of the literature. The
      dilated loop of the jejunum was drained percutaneously with 10 F abscess drainage
      catheter. The obstructive jaundice was improved.

PMID- 14661304
TI  - [Case report: Complex composite odontoma: Plain radiography and computed
      tomography findings].
AB  - Complex composite odontoma is a rare benign odontogenic hamartoma seen in
      association with a primary tooth. Although it is seen most frequently between 10
      19 years of age, here we present a lesion of unusual size in the mandible of a 6
      year-old boy and report its clinical, radiographic, CT and histologic findings.
      Also, we discuss the value of three dimensional images.

PMID- 14661305
TI  - [Case report: Rhizomelic chondrodysplasia punctata and foramen magnum stenosis in
      a newborn].
AB  - Chondrodysplasia punctata is a peroxisomal disorder which is a form of multiple
      epiphyseal dysplasia. It is characterized by calcifications of unossified
      cartilaginous epiphyseal centers during the first year of life. Severe autosomal
      recessive rhisomelic form shows bilateral proximal shortening of the upper and
      lower limbs with punctate epiphyseal calcifications. We report radiological
      findings of a patient with rhisomelic chondrodysplasia punctata. Magnetic
      resonance imaging showed foramen magnum stenosis that caused spinal cord
      compression.

PMID- 14661306
TI  - [Case report: Acute abdomen and pelvic mass due to torsion of a wandering
      spleen].
AB  - Torsioned wandering spleen should be considered in patients who have an
      intrapelvic mass with acute abdominal symptoms. Nowadays, color Doppler US and CT
      are easily achievable and are highly accurate for indicating the correct
      diagnosing in such patients. Using these two modalities together will increase
      the ability for correct diagnosis.

PMID- 14661307
TI  - [Primitive neuroectodermal tumor of the chest wall (Askin tumor)].

PMID- 14661308
TI  - [Arteriovenous malformations mimicking dilated medulla oblongata veins in Sturge
      Weber syndrome].

PMID- 14661309
TI  - [Duodenal atresia: prenatal ultrasonic evidence].

PMID- 14661310
TI  - [Myositis ossificans circumscripta].

PMID- 14661311
TI  - [Quadrigeminal cistern lipoma: MRI findings].

PMID- 14661312
TI  - [Abscess formation indicating idiopathic granulomatous mastitis].

PMID- 14661313
TI  - [Intradural extramedullary lipoma].

PMID- 14661314
TI  - [Plantar fibromatosis].

PMID- 14661315
TI  - [Ovarian clear cell tumor].

PMID- 14661316
TI  - [Complex type Caroli disease: radiologic findings].

PMID- 14661317
TI  - [Splenic abscess imitating an accessory liver lobe].

PMID- 14661318
TI  - [Antenatal ovarian cysts].

PMID- 14661319
TI  - [Analysis of patient's satisfaction with the mandibular implant-borne
      overdentures].
AB  - OBJECTIVE: To compare the subjective attitudes of fully edentulous patients in
      mandible toward the implant-borne overdentures and toward the previous complete
      dentures. METHODS: 16 fully edentulous patients in mandible were consecutively
      included in this study and the attitudes toward the implant-borne overdentures
      and the previous complete dentures were surveyed through questionnaires at the
      first visit and after the implant prosthesis. RESULTS: There exists significant
      difference regarding to the comfort, function and fixedness between implant-borne
      overdentures and the previous complete denture. CONCLUSION: It was revealed that
      mandibular bar-clip retention implant-borne overdentures can highly fulfill
      patient's demands.

PMID- 14661320
TI  - [A study on the epidemiology of permanent tooth carles in children aged 15 years
      in Anhui province].
AB  - OBJECTIVE: The first study on the epidemiology of oral health status in AnHui
      province was held. The purpose of this survey was to investigate the prevalence
      of dental diseases and the needs of dental treatment, so as to develop effective
      programs in providing dental care in children. METHODS: Non-proportional
      stratified cluster sampling was used for this study. RESULTS: The results showed
      that XDMFT in this group was 0.95, permanent caries prevalence rate was 39.78%,
      lower than that of the same age children in other 11 provinces in Mainland(P <
      0.001). The proportion of DMFT was 86.78%(D), 4.30% (M), 8.92% (F), respectively.
      The caries number that needed dental care were 1842 teeth(0.78 teeth per person).
      CONCLUSION: The caries prevalence rate, the XDMF and the "F" were lower than the
      same age children in 11 provinces in Mainland and the "M" was higher.

PMID- 14661321
TI  - [Study of esthetic characteristic changes of soft tissue profile of patients with
      Angle Class division 1 malocclusion treated by functional regulator].
AB  - OBJECTIVE: Five esthetic indexes were used to evaluate the soft tissue profile
      changes of patients with Angle Class division 1 malocclusion treated by
      Functional Regulator. METHODS: 21 patients with Angle Class division 1
      malocclusion were treated by functional regulator. Pretreatment and posttreatment
      cephalograms of every patient were traced to analyze the esthetic characteristic
      of soft tissue profile. RESULTS: Most of the indexes tended to normal after
      treatment. CONCLUSION: Soft tissue profile of most patients with Angle Class
      division 1 malocclusion was improved after functional orthopedics while changes
      were different individually. Second stage treatment was still required for some
      patients.

PMID- 14661322
TI  - [Study of midazolam for premedication in oral and maxillofacial surgery].
AB  - OBJECTIVE: To study the effects of midazolam for premedication in oral
      maxillofacial surgery. METHODS: 60 patients were selected and divided into 3
      groups equally with 20 cases in each group. Different drugs were used for
      premedication. Group received midazolam 0.06 mg/kg, group received diazepam 0.12
      mg/kg, group received luminal 3 mg/kg, Intramuscular injections of drugs were
      finished before 30 minutes of anesthesia. The sedative and anxiolytic effects,
      the changes of circulation and respiration and the side effects were evaluated.
      RESULTS: In group, BIS (bispectral analysis of electroencephalogram) decreased
      obviously and Ramsay score increased significantly 5 minutes after drug
      administration, AVAT(Anxiety visual analog test) and SAI(State anxiety inventory)
      decreased obviously 30 minutes after administration drug (P < 0.05). But no
      significant changes in the other groups (P > 0.05). There were no remarkable
      changes of circulation and respiration in the three groups. No severe side
      effects were observed after premedication. CONCLUSION: The premedication of using
      midazolam has good sedative and anxiolytic effects and few side effects.

PMID- 14661323
TI  - [Single-tooth replacement in the aesthetic zone with immediate
      provisionalization].
AB  - OBJECTIVE: To investigate the clinical results of immediate loading of a single
      anterior implant. METHODS: 8 Frialit-2 implants were placed into anterior sites.
      Provisional prosthesis were placed at the time of fixture placement. RESULTS: No
      fixture has been lost since the immediate restoration was delivered, the minimum
      being 7 months and the maximum 14 months. CONCLUSION: Clinical studies on the
      placement of immediate restoration in anterior implant have revealed predictable
      results.

PMID- 14661324
TI  - [The experimental study of cryopreserved osteoblasts combined with BGC repairing
      mandibular defects in rabbits].
AB  - OBJECTIVE: The purpose of this study was to observe the biological
      characteristics of cultured Periosteal-derived Osteoblasts (POBs) preserved in
      liquid nitrogen in vitro, and to preliminarily study the osteogenetic capability
      of bioactive glass ceramic (BGC) combined with POBs. METHODS: The cryopreserved
      cells were cultured in DMEM medium and examined by morphological and histological
      assay. The POBs growing well in vitro were seeded into the porous BGC materials.
      A week later, the combined materials were implanted into the bone defects of
      rabbits' mandibular, the control groups were implanted into the single BGC (no
      cells). After 2, 4, 8, 12 weeks of operation, the specimens were respectively
      excised and examined by X-ray and histological chemistry. RESULTS: The
      cryopreserved POBs grew well in vitro and also had the tipical characteristics of
      mature osteoblasts. Cultured with BGC materials, the cells could attach, grow and
      proliferate well on the surface of most endoporous. After 4 weeks of operation,
      the transplanted osteoblasts began to form new osteoid or bone tissue in most
      pores of implanted BGC, and the bone defects were repaired better and earlier.
      CONCLUSION: It was practical to use the cryopreserved osteoblasts for further
      study on bone tissue engineering. It suggested that the "life active" bone would
      get more application and play a more important role in bone restoration and
      reconstruction.

PMID- 14661325
TI  - [Comparison of synthesizing Collagen I and III in periodontal ligament cells and
      gingival fibroblasts].
AB  - OBJECTIVE: To investigate the different characteristics of periodontal ligament
      cells and gingival fibroblasts in synthesizing Collagen I and III. METHODS:
      Periodontal ligament cells and gingival fibroblasts were cultured from the same
      patient and detected for expression of Collagen I and III by immunocytochemical
      methods. RESULTS: The immunocytochemical staining showed Collagen I and III were
      positive in periodontal ligament cells, and mild positive in gingival
      fibroblasts. Statistical analysis suggested the difference between gingival
      fibroblasts and periodontal ligament cells. CONCLUSION: There were differences
      between the periodontal ligament cells and gingival fibroblasts in synthesizing
      or secreting of Collagen matrix.

PMID- 14661326
TI  - [The effect of sodium hyaluronate on the rabbit osteoarthrosis].
AB  - OBJECTIVE: To study the effect of high-molecular-weight sodium hyaluronate on
      rabbit osteoarthrosis, which was made by immobilizing the temporomandibular
      joint. METHODS: 18 common rabbits were equally divided into 2 experimental groups
      and 1 control group. After the rabbit temporomandibular joint were immobilized,
      0.06 ml high-molecular-weight sodium hyaluronate were injected into the left TMJs
      while the same amount of physiological Saline into the right ones. The animals
      were terminated after 2 weeks and 4 weeks respectively. The whole bilateral TMJs
      were removed and histopathological and histochemical examinations were performed
      to evaluate the changes of articular cartilage and the content of
      glycansaminoglycan in articular cartilage. RESULTS: There were severe
      osteoarthrotic changes in the right TMJs, whereas the changes in the left ones
      were slight. There was a significant difference between them (P < 0.01).
      CONCLUSION: High-molecular-weight sodium hyaluronate can restrain the
      degenerative changes of the immobilized TMJs.

PMID- 14661327
TI  - [Expression of vascular endothelial growth factor during mandibular distraction
      osteogenesis in rabbits].
AB  - OBJECTIVE: To investigate the expression pattern of vascular endothelial growth
      factor (VEGF) in the distracted callus during mandibular osteodistraction.
      METHODS: Bilateral mandibular osteotomies were performed in 12 rabbits. 3 rabbits
      were sacrificed respectively at 0, 7, 14 and 28 days after completion of
      distraction. The newly formed calluses were harvested and processed for histology
      and immunohistochemistry of VEGF. RESULTS: Intense angiogenesis was observed in
      the regenerated callus after mandibular lengthening, and positive staining for
      VEGF was mainly noted in vascular endothelial cells and the active osteoblasts.
      CONCLUSIONS: Mechanical strain created by distraction led to angiogenesis in
      distraction gap. VEGF may play a critical role in angiogenesis and subsequent
      osteogenesis during mandibular lengthening.

PMID- 14661328
TI  - [Effect of intravenous administration of monoantibody to P-selectin on the
      distribution of ACC-M adhesion in lung].
AB  - OBJECTIVE: To investigate the effect of intravenous administration of
      monoantibody to P-selectin (PS1) on the lung-metastasis characteristic of highly
      lung metastatic adenoid cystic carcinoma cell strain (ACC-M). METHODS: 3HTdR
      labeled ACC-M cells were injected intravenously through tail vein after using
      monoantibody to P-selectin. A mice of each group were killed at 2 h, 6 h and 18 h
      after infusion, respectively. The relative radioactivity (CPM) in the lung and
      liver was detected. RESULTS: 3H-activity per gram in lung of mAb group was lower
      than in control group. There was significant difference between the two groups (P
      < 0.001). There was no difference between the two groups of liver tissues (P >
      0.005). CONCLUSIONS: The results of this study suggested that the highly lung
      metastasis characteristic of ACC-M may be partially inhibited by the use of
      monoantibody to the P-selectin.

PMID- 14661329
TI  - [A comparative study of root smear layer removal using different pH EDTA salts].
AB  - OBJECTIVE: To evaluate the effect of different pH EDTA salts on removing root
      canal smear layers. METHODS: Sixty human teeth with single root were instrumented
      using step-back technique, then were irrigated with several irrigating solutions
      including A: 0.9% saline; B: 5.25% NaOCl +3% H2O2; C: 15% EDTA (pH = 6.5); D: 15%
      EDTA (pH = 13); E: 15% EDTA (pH = 6.5) 25% NaOCl +3% H2O2; F: 15% EDTA (pH = 13)
      25% NaOCl +3% H2O2. After the teeth were split, the root canal walls were
      examined with scanning electron microscopy at the coronal, middle and apical
      thirds for smear layer removal. RESULTS: Except A and B group, all the groups
      were effective on removing smear layer at the coronal, middle thirds of the root
      canal, group C had a stronger effect to remove smear layer than group D (P <
      0.05), group E was the most effective among these groups. However, these groups
      were all ineffective on removing smear layer at the apical thirds of root canal.
      CONCLUSIONS: 15% EDTA (pH = 6.5) 25% NaOCl +3% H2O2 was the most effective
      irrigation on removing smear layer.

PMID- 14661330
TI  - [Inhibiting effect of EGFR monoclonal antibody on proliferation of oral squamous
      cell carcinoma].
AB  - OBJECTIVE: To investigate the inhibiting effect of epidermal growth factor
      receptor (EGFRmAb) on proliferation of oral squamous cell carcinoma (SCC).
      METHODS: Tca8113 squamous cell carcinoma cell line was treated with different
      concentration of EGFRmAb. Cell growth curve, clone inhibition rate, cell cycle
      redistribution and the expression of p27kip1 were analyzed. RESULTS: EGFRmAb
      inhibited proliferation of oral SCC, leaded to elevation of cell proportion of
      G1phase cell, decreased the proportion of S phase cell and upregulated the
      express of p27kip1. CONCLUSION: EGFRmAb inhibited the proliferation of oral SCC,
      which related with G1 phase arrest of tumor cell.

PMID- 14661331
TI  - [Analysis and discuss of trace elements in the teeth].
AB  - OBJECTIVE: Through the analysis and discussion of some trace elements in human's
      teeth, many related information were offered towards the researches and the cure
      in teeth diseases. METHODS: Using the ICP-AES method, some trace elements such as
      Cu, Zn, Cr, Mn, Fe, Al and Sr were determined respectively and the interfere
      caused by the principal element calcium to the above elements in this
      determination were studied. On the other hand, the changes of these trace
      elements were discussed between the normal teeth and the decayed teeth and the
      different ages and genders. RESULTS: It was found that the content of Cu was out
      of and that of Al was in direct and that of others elements were in inverse
      proportion to one's age; the ranges of content of all determined elements in the
      different age groups were as follows: Sr 70-226 micrograms/g, Zn 74-157
      micrograms/g, Al 37-58 micrograms/g, Fe 3.24-11 micrograms/g, Cr 3.03-6.40
      micrograms/g, Mn 2-3.39 micrograms/g and Cu 0.18-1.53 micrograms/g; the content
      of Sr in the female's teeth was obviously and that of Fe, Mn, Zn, Al were
      slightly higher than in male's, whereas the contents of Cu and Cr in the two
      genders were mainly consistent. CONCLUSION: Trace elements in teeth are a factor
      to indicate sorts of teeth diseases and provide the scientific references for
      some researches in teeth diseases.

PMID- 14661332
TI  - [Chewing gum and caries].

PMID- 14661333
TI  - [Perioperative management of the patients with obstructive sleep apnea syndrome].

PMID- 14661334
TI  - [Recent development of the research on immunization against dental caries for
      controlling mutans streptococci].

PMID- 14661335
TI  - [Localization of the impacted teeth using dentomaxillary pantomography].

PMID- 14661336
TI  - [Investigation of prevention and treatment of dental caries for 3 schools in
      Shanghai Jinshan District].

PMID- 14661337
TI  - [A clinical analysis on the treatment of the pulp chamber penetration with bio
      oss bone powders].

PMID- 14661338
TI  - [Partial parotidectomy without ligation of the parotid duct in the treatment of
      parotid benign tumors].

PMID- 14661339
TI  - [The clinical attempt to complete the implant operation of 2-stage implant at the
      same time].

PMID- 14661340
TI  - [An analysis of the causes of titanium plates removal after rigid internal
      fixation for jaw fractures].

PMID- 14661341
TI  - [A clinical study of the difference in the application of soft and hard relining
      materials for complete denture].

PMID- 14661342
TI  - [Clinical observations of the porcelain veneers in 20 cases].

PMID- 14661343
TI  - [The occurrence of the endodontic interappointment emergencies after root canal
      preparation by step back or step down technique].

PMID- 14661344
TI  - [The effect of pit and fissure sealants in teeth filling with silver amalgam].

PMID- 14661345
TI  - [Application and evaluation of Vitapex Plus Reoko in induction apexification].

PMID- 14661346
TI  - [Challenges and perspectives of veterinary public health].
AB  - This article presents the conceptual basis for veterinary public health-VPH,
      including historical aspects of its constitution and development, its fields of
      action, and its current challenges. It also presents a reflection on VPH within
      the frame of the veterinary services and it finally proposes that education plays
      a fundamental role in order to face the challenges of a new era.

PMID- 14661347
TI  - [Prevalence and factors associated with suicidal thinking among university
      students].
AB  - OBJECTIVES: To quantify the prevalence of suicidal ideation in a population of
      university students, to characterize groups in connection with ideation and
      suicidal behavior, and to determine the variables associated with suicidal
      ideation and suicide attempts. METHODS: Observational, analytic and cross
      sectional study of a probabilistic sample of the population studied. An
      instrument for measuring suicide risk and associated variables was applied to
      this sample. RESULTS: The prevalence of the current suicidal ideation was 3.6%,
      and 18% in the last year. Both suicidal ideation and history of suicide attempts
      were higher among female students. Rape history, being alone more than eight
      hours a day, and female gender were the factors more strongly related to suicidal
      ideation. A relationship suicidal ideation and awareness of the suicide of others
      was not found in this sample. CONCLUSION: A history of rape, remaining alone for
      more than eight hours during the day, and being a woman should alert the
      clinician about the possibility of suicidal ideation. It is recommended to
      explore and assess suicidal ideation in all people with these factors.

PMID- 14661348
TI  - [Evaluation of the National Vaccination Day in Bogota, D.C., 2001].
AB  - OBJECTIVES: A national immunization day-NID, aimed at improving vaccination
      coverage, was carried out in Colombia in November 2001. The main objective of the
      study was to measure the proportion of children under 2 years either completing
      their immunization schedule or advancing through it by receiving doses during the
      NID. Besides, we also evaluated the proportion of lost opportunities for
      vaccination during the NID and the impact of the media (TV, ratio, newspapers,
      etc.) in advertising the NID. METHODS: In order to evaluate the impact of
      immunization a cross sectional survey was carried out in Bogota in the waiting
      rows of the 30 randomly selected vaccination posts; 623 participants were
      systematically chosen. The outcomes were analyzed by age, socioeconomic level and
      type of health insurance-SSS. Only children holding a vaccination card were
      considered eligible for the study. RESULTS: Most people become aware about NID
      through TV, 81%, followed by radio advertisements, 22%. After attending NID the
      proportion of fully vaccinated children, according to PAHO scheme, raised from
      46% to 66%, a 43% increase. This increase was even higher among children aged
      less than 6 months (140% increment). There were no differences in the increment
      by social stratum or affiliation to the SSS. Among the children studied we
      identified a 24% of loss opportunities for vaccination that did not differ by
      socioeconomic level or SSS groups. CONCLUSIONS: Our results suggest that, despite
      its high costs, NID might be useful to transiently overcome barriers for adequate
      access to health services.

PMID- 14661349
TI  - [Mortality from traffic accidents in the Tunja-San Gil road area, Colombia,
      2001].
AB  - OBJECTIVES: To identify the characteristics of mortality related to motor vehicle
      accidents in the Tunja-San Gil area (Colombia) in the year 2001. METHODS: A
      descriptive study was performed on the deaths from road accidents. Autopsy
      reports, body removal reports, death certificates and blood concentration
      reports, available at the National Institute for Forensic Sciences and at the
      local hospitals, were reviewed. RESULTS: Forty five fatalities were analyzed. The
      mean age of the victims was 34.7 years; males were more affected than females,
      with a 3:1 ratio. 37% were pedestrians, 26% motorcyclists, 20% drivers, 8.6%
      cyclists and 8.6% passengers. 65.1% of the road accidents occurred during
      weekends. The most common road accidents were either collisions or by running
      over. The places with the highest rates of death from motor vehicle related
      accidents were the urban areas of Tunja and San Gil and the Vado Real-Oiba road.
      The mean Injury Severity Score was 42.8. 53% of the deaths at the scene received
      no medical care; 73% of the victims died within two hours after the motor-vehicle
      accident. 17.8% of deaths were definitely preventable and 46.7% were possibly
      preventable, for a combined preventable death rate of 64.5%. CONCLUSIONS: It is
      necessary to develop and implement a road-accident related-trauma care system.

PMID- 14661350
TI  - [Mathematical model for the analysis of vaccination and vector control in malaria
      incidence].
AB  - OBJECTIVES: A model describing malaria behavior through a system of ordinary
      differential equations. METHODS: In order to construct the model, the interaction
      between man and the malaria vector was taken into account in different
      infectivity and immunity states. We also considered the vaccination effect by
      means of an infection blocking vaccine and parameters representing larval and
      adult vector control. RESULTS: The model developed enables simulation of malaria
      disease behavior in various settings: in a natural manner without intervention,
      with either vector control or vaccination, and considering vector control and
      vaccination together. CONCLUSIONS: We obtained numerical conditions for the
      existence of a non-trivial equilibrium state, conditioned to the existence of a
      single real positive root of a fourth degree polynomial. This is a problem that
      remains unsolved.

PMID- 14661351
TI  - [Evaluation indicators of the Healthy Municipalities for Peace strategy in
      Colombia].
AB  - OBJECTIVES: The work that is presented is the first phase of a scale development
      study. The objectives are: selecting, developing and evaluating indicators for
      the evaluation of the healthy cities project in Colombia, in order to offer the
      bases for the construction of a measurement scale. METHODS: The project was
      executed from January 2001 to August 2002. A validation by construct and an
      assessment of indicators, according to their importance, data availability and
      formulation were carried out. A theoretical heuristic model for evaluating the
      Colombian Healthy Cities Project was developed; based on these model 128
      indicators were defined. A preliminary instrument was then made and evaluated by
      experts in the strategy. A test was carried out in five cities in order to test
      data availability and formulation. RESULTS: The final results are a heuristic
      model for the evaluation of the project and an evaluation of each indicator.
      CONCLUSIONS: The final results are not finished. A greater effort is needed for
      developing good heuristic models and for building instruments for assessing the
      healthy cities project in Colombia.

PMID- 14661352
TI  - [Surgery needs to change].

PMID- 14661353
TI  - [Abdominal aneurysm resection in aged patients at the Surgery Clinic in Plzen
      from 1998 to March 2003].
AB  - The authors evaluate resection therapy on aneurysms of abdominal aorta in
      patients of high age (mean 85 years) at the Clinic of Surgery in Plzen. In the
      period of 1998-March 2003 the authors performed 13 elective resections on
      aneurysms of abdominal aorta in patients of high age with zero mortality and 21
      acute resections with 38% mortality. In the given period of time, 178 resections
      of aneurysms of abdominal aorta were made in patients younger than 78 years, 57
      being acute interventions. Mortality of elective interventions was 2.9%, in acute
      interventions being 28%. The present groups indicate that mortality of resection
      therapy sharply increased in relation to circulation instability of the patients
      in cases of ruptured aneurysm, but nor in relation to age of the patients.

PMID- 14661354
TI  - [Pedal bypass versus PTA (percutaneous transluminal angioplasty) of the crural
      arteries].
AB  - Diabetic foot syndrome in patients with atherosclerotic angiopathy of the crural
      arteries frequently develops in critical ischaemia and gangrene.
      Revascularization then may be the only approach to limb salvage. In the ongoing
      decade, pedal bypass grafting has become the method of choice for treatment of
      the most severe forms of chronic critical leg ischaemia caused by obliteration of
      the crural arteries. However, in patients in whom angiographic findings are
      favourable (short stenosis of the crural artery and the presence of suitable
      distal outflow arteries), percutaneous transluminal angioplasty (PTA), with stent
      placement, if indicated, is preferred. In multisegmental or diffuse disease or
      when PTA is associated with complications (occlusion or dissection) with
      subsequent limb ischaemia, bypass surgery is the method of treatment. In this
      study, the group of 30 patients undergoing bypass grafting showed 90% patency of
      the pedal bypasses at 12-month follow-up; in 18 patients treated by PTA, the
      patency of crural arteries at 6 months after angioplasty was 78%. Since either
      method has its advantage and disadvantages, an individual approach to each
      patient is recommended. In decision-making on the basis of angiographic findings,
      PTA is not confronted with pedal bypass grafting but the two methods are regarded
      as complementary in treatment of patients with crural artery disease.

PMID- 14661355
TI  - [Surgical treatment of paraesophageal hernia].
AB  - Four types of hernia may occur in the area of esophageal hiatus. Type I is
      represented by hiatus slipping hernia. Type II is represented by hernia, which is
      generally known as paraesophageal hernia. In this type of hernia, cardia and
      distal stomach remain under diaphragm. The weakened tissue in phreno-esophageal
      membrane is the place, where stomach fundus penetrates into thorax above the
      diaphragm. The authors present 10 patients with paraesophageal hernia, who were
      operated on at the 2nd Surgery Clinic of Medical Faculty, UPJS, Faculty Hospital
      L. Pasteur in Kosice. These were adult patients, five man and five women. In four
      patients, so called "upside-down stomach" was the case. Hernias were operated on
      in all cases by laparotomy, after reposition of the stomach into abdominal cavity
      the area of hiatus and diaphragm was reconstructed. One patient was operated on
      under emergency conditions for bleeding from stomach ulcer. Immediate
      postoperation results were good, the postoperation course was favorable in all
      patients, no complications occurred. In conclusion, the authors are of the
      opinion that every diagnosed paraesophageal hernia should be indicated for
      surgical intervention. An anti-reflux operation should be executed in symptoms of
      gastro-esophageal reflux. The question of operation approach (thoracotomy or
      laparotomy) is a matter of continuous discussion, each of them having its
      advocates. However, in recent years laparoscopic solution of paraesophageal
      hernia is getting increasing attention.

PMID- 14661356
TI  - [Anatomic deviations in the origin of the median nerve].
AB  - OBJECTIVE: Deviations detected during the operation triggered our interest to
      start work dealing with variations in the formation of n. medianus GROUP: One
      hundred brachial plexuses were examined in order to detect variations of n.
      medianus. Attention was paid to the course and anastomoses. RESULTS: In 32 cases
      (64%) the authors observed 40 deviations. The deviations occurred more frequently
      on the left in 16 cases. They were most frequently of anastomosis character.
      CONCLUSION: The study made it possible to detect and describe deviations in the
      formation of n. medianus up to the lower third of shoulder.

PMID- 14661357
TI  - [Adenocarcinoma of the small intestine].
AB  - Tumors of the small bowel are seldom course of gastrointestinal malignity. The
      small bowel tumor occurrence represents 1-5% in world literature. Good prognosis
      and five year survival depend on early diagnose and radical surgical treatment
      with consequential multimodal therapy. Our patient's case documents the diagnose
      difficulties and its possibilities.

PMID- 14661358
TI  - [Solid papillary neoplasia of the pancreas--case report].
AB  - Solid papillary neoplasia of the pancreas is a rare tumour that occurs most
      commonly in young women. This tumour has low malignant potential and favourable
      prognosis following surgical resection. Therefore it is mandatory to distinguish
      this tumour from other types of pancreatic tumours. The paper reports the case of
      a 31-year-old woman with a large solid papillary neoplasia of the head of
      pancreas where successful pancreatoduodenectomy was performed.

PMID- 14661359
TI  - [Ulnar-carpal impingement after fractures of the distal radius].
AB  - The authors describe the group of 23 patients (16 women, 7 men), who were
      operated during 2000-2003 on ulna-carpal impingement or the syndrome of ulna
      impact on the basis of "plus variant" of ulna or also "long ulna". There was a
      fracture of distal radius in anamnesis of all these patients. The condition was
      solved in 18 patients (mean age 51 years) by reducing the ulna by 4.5 cm on the
      average (range 2-10 mm). In five patients (mean age 49 years), the radius-ulna
      desis sec. Sauve-Kapandij was performed. The results are evaluated with the time
      lapse of 6 months on the average (range 3-26). The resulting evaluation indicates
      that in all patients, who were not affected by radius-ulna arthrosis, a simple
      reduction of ulna resulted in an improvement of the extent of movements and
      improved subjective complaints. Patients with radius-ulna arthrosis, where the
      ulna-carpal impingement was solved by radius-ulna desis, suffer from worse long
      term functional results. The authors also analyze complications of the
      interventions. Posttraumatic deformations in the area of distal forearm should be
      solved early before degenerative changes develop. The is the only way how to
      expect good results of the operation and favorable effect for the patient.

PMID- 14661360
TI  - [Detection of CagA protein in strains of Helicobacter pylori isolated from
      patients with gastritis and gastric ulcer disease].
AB  - A total of 156 Helicobacter pylori strains isolated from adult patients (81 men,
      75 women) with diagnosis of gastritis (43 strains GAS) and gastric ulcer (113
      strains GU) were analyzed for the production of CagA protein by quantitative and
      qualitative immunoblot methods. 80% of gastric ulcer group strains (84% in men,
      73% in women) produced CagA protein, while in the gastritis patients group only
      63% of strains were CagA protein positive (59% in men, 65% in women).
      Quantitative production was estimated by CagA index (mean production of CagA
      protein in CagA positive strains) in both groups of strains GAS and GU in men and
      women. Strains of GU group were shown to be higher producers (index CagA 2.42) as
      compared to GAS group (2.09). Index CagA was higher in strains isolated from men
      (index CagA 2.54) than is strains from women (index CagA 2.13). CONCLUSION: CagA
      production has been proved in 75% of analysed Helicobacter pylori strains. CagA
      positive strains were more frequent in gastric ulcer disease patients, slightly
      higher in the male than in the female patients. Strains isolated from men,
      irrespective of diagnosis (GAS and GU), are higher producers of CagA protein.

PMID- 14661362
TI  - [Bacterial cellular communication in relation to pathogenicity].
AB  - The authors briefly summarize data on cell-cell communication (quorum sensing) as
      well as principles of simple methods for detection of N-acyl homoserine lactones.

PMID- 14661361
TI  - [Serologic study of atherosclerosis and its vascular complications].
AB  - Chlamydia pneumoniae (C. p.) is very frequently cited as an important factor of
      the origin of atherosclerosis. To confirm the diagnostic value of the serological
      examination the following reactions have been used: microimmunofluorescence
      reaction (MIF) for estimating of antibodies against major outer membrane proteins
      C. p. (anti-MOMP) and ELISA for detecting antibodies against the
      lipopolysacharides of C. p. (anti-LPS), both in IgA and IgG immunoglobulin
      classes of the serum. The ELISA for the detection of the IgG antibodies against
      chlamydial heat shock protein (cHSP60) has been used. The sera of 155 patients
      suffering from acute myocardial infarction (AMI) and 69 patients with unstable
      angina pectoris (UAP) have been examined. The heart disease has been confirmed by
      anamnesis, electrocardiography and coronarography. As a control group the sera
      from 112 persons without sings of a heart disease were examined. The antibodies
      against the cHSP60 have been determined only in the sera 69 patients with UAP and
      49 control sera. Statistically higher occurrence of the antibodies anti-MOMP C.
      p. in the IgA class sera of patients suffering from UAP has been noted compared
      with those found in the sera of the control group (chi 2 = 18.56; p < 0.01). In
      the globulin IgG class of the both groups no difference has been found. The anti
      LPS C. p. antibodies in the IgA as well in IgG anti-LPS classes of the patients
      sera with UAP were present significantly more frequently than in the control
      group (chi 2 = 11.49; p < 0.01, chi 2 = 4.16; p < 0.05). Similarly the incidence
      of the anti-LPS C. p. antibodies in the IgA class sera of 155 patients suffering
      from AMI was significantly higher than in the control group (chi 2 = 8.55; p <
      0.01). The anti-cHSP60 antibodies have been found in 41 out of 69 patients
      suffering from UAP (59.4%) and in 21 of 49 control individuals (42.9%). The
      results seem to confirm an important role of C. p. in atherogenesis. The
      monitoring of the antibodies against the C. p. may supplement the diagnostics in
      patients suffering from UAP and AMI and the efficacy of its therapy and
      prevention as well.

PMID- 14661363
TI  - [Comments on attempts for health care reform in public health].

PMID- 14661364
TI  - [The dangerous and the unfortunate].

PMID- 14661365
TI  - [A new strategy for monitoring levels of cyclosporin A in the blood of patients
      after kidney transplantation].
AB  - Cyclosporine A (CyA), tacrolimus (FK 506), and mycophenolic acid are routinely
      utilised immunosuppressive drugs used in the prevention of allograft rejection
      and the treatment of several autoimmune diseases. The monitoring of CyA blood
      levels plays the most important role to individualize the dosage regiment and to
      minimize acute rejection risk and drug toxicity. Inadequate low CyA doses and
      levels may result in the rejection of transplanted organs. Toxic levels of CyA
      are associated with many serious side effects, including nephrotoxicity,
      hepatotoxicity, and a range of other complications. In the period of 1999-2002,
      12,859 analyses of whole blood CyA levels were performed at our Department of
      Clinical Biochemistry. The aim of the present paper is to establish a new
      monitoring strategy of CyA that consists in the use of a single sampling point at
      2 hours postdose and the estimation of blood concentration (C2). For the
      transplant patient, C2 monitoring is a significantly much better predictor of
      drug exposition and pharmacokinetic estimation than the trough concentration
      monitoring before the next dose (C0) used until now. The C2 monitoring strategy
      reduces the incidence and severity of both acute organ rejection and cyclosporine
      A toxicity.

PMID- 14661367
TI  - [Biologically active benzoxazoles].
AB  - This review presents a survey of preparations and biological activities of
      substituted benzoxazoles. The structural similarity of benzoxazole derivatives
      with nucleic bases, such as adenine and guanine, probably allows their easy
      interaction with biopolymers in the living systems. Consequently, these compounds
      posses a wide range of biological activities. Their preparation includes
      cyclocondensation reactions and contractions of ortho-fused heterocycles or their
      photochemical rearrangement. They are being studied predominantly for their
      antibacterial, antifungal, antiviral, and antitumor activities, and also as
      insecticides, herbicides, anthelmintics, histamine antagonists, and fluorescent
      dyes.

PMID- 14661366
TI  - [Biological effects of resveratrol and other constituents of wine].
AB  - In recent years many scientific papers have been published concerning the
      positive effects of wine and its active principles, the polyphenol resveratrol
      being the most widely discussed compound. The results of epidemiological and
      experimental studies in man, animals, and in vitro have shown that polyphenols
      contained in wine, tea, fruit, and vegetables exert a positive effect on both the
      progression and regression of atherosclerosis, possess an anticancerogenic
      action, and due to their antioxidative effects they act against other processes
      connected with the reactive forms of oxygen production and lipid peroxydation in
      the blood plasma and membranes. Experimental findings have shown that resveratrol
      protects the cardiovascular system, affects lipid metabolism, and inhibits low
      density lipoproteins (LDL) oxidation and blood platelet aggregation. In addition,
      this natural product is able to inhibit the growth of some tumours and possesses
      antiinflammatory properties and a number of other biological effects. This report
      aims to describe and characterize in a summary the biological properties of the
      principal active principles of wine--flavonoids and polyphenols, with a detailed
      focus on resveratrol, which has been described as the most interesting agent.

PMID- 14661368
TI  - [A new group of potential antitubercular agents: antimycobacterial N
      benzylsalicylamides].
AB  - Linking up with a previous study of antimycobacterial compounds, several groups
      of N-benzylsalicylamides were prepared and their antimycobacterial activities
      against the strains Mycobacterium tuberculosis, Mycobacterium kansasii, and
      Mycobacterium avium were evaluated. The obtained data were analyzed by Free
      Wilson method in comparison with their isosteric analogues of 3-hydroxypicolinic
      and 2-sulfanylbenzoic acids described in the previous communication.

PMID- 14661369
TI  - [Release of diltiazem chloride and ibuprofen from hydrophilic matrix tablets].
AB  - Hydrophilic matrix tablets based on hydroxypropylmethylcellulose (HPMC) and other
      cellulose derivatives rank among dosage forms with retarded effect widely used in
      contemporary pharmacotherapy. The active ingredient is released from them in
      dependence on its properties either by dissolution and diffusion, or erosion of
      the compact. The dissolution profile of the active ingredient can be influenced
      by variables of formulation and manufacture, e.g. by the type of HPMC employed,
      its concentration, other added auxiliary substances, and compression force which
      is reflected in the strength of tablets. Two drugs with different solubility were
      used to study the effect of drug solubility on its release from matrices: well
      soluble diltiazemium chloride and badly soluble ibuprofen. Higher solubility of
      the drug and lower solubility of compacts resulted in more rapid release of the
      active ingredient. Also lower concentration of HPMC accelerates the release of
      both drugs. The effect of the degree of viscosity of the polymer on drug release
      was not markedly manifested.

PMID- 14661370
TI  - [Solubilization of unilamellar egg yolk phosphatidylcholine liposomes by N-alkyl
      N,N-dimethylamine N-oxides].
AB  - The solubilization of extruded (100 nm) unilamellar egg yolk phosphatidylcholine
      (EYPC) liposomes by a series of N-alkyl-N,N-dimethylamine N-oxides (CnNO, n = 10
      14 carbon atoms in the alkyl substituent) was studied using turbidimetry. The
      solubilizing concentration of CnNO (cS) was estimated as the CnNO concentration
      causing the half-maximum decrease in turbidance. From the linear cS dependence on
      EYPC concentration, the lipid--aqueous phase molar partition coefficient (Kp) and
      the CnNO:EYPC molar ratio in the CnNO + EYPC aggregates (nL:nEYPC) at cS were
      obtained: Kp = 82 +/- 25 and nL:nEYPC = 0.70 +/- 0.20 for C10NO, Kp = 507 +/- 215
      and nL:nEYPC = 0.60 +/- 0.16 for C12NO, and Kp = 12357 +/- 93 and nL:nEYPC = 1.13
      +/- 0.01 for C14NO. The value of Gibbs free energy of CnNO alkyl methylene group
      transfer from the aqueous to the lipid phase calculated from the Kp dependence on
      n is -1.2 +/- 0.2 RT (R = gas constant, T = absolute temperature), within the
      experimental error being the same as -1.026 +/- 0.006 RT obtained from the
      critical micellar concentrations of CnNO. The increased value of nL:nEYPC for
      C14NO is caused by the decreased hydrophobic mismatch of CnNO and EYPC
      hydrocarbon chain lengths. This mismatch results in a structural defect in the
      bilayer hydrophobic core, the primary cause of bilayer destabilization and
      solubilization.

PMID- 14661372
TI  - European contributors.

PMID- 14661371
TI  - [Anticomplement activity of saponins from Cynara cardunculus L].
AB  - Triterpene saponins of ursane and oleane type isolated from the involucral bracts
      of Cynara cardunculus L. (Asteraceae) were investigated in in vitro assays for
      their activity on the complement system. The anticomplementary activity of
      bidesmosidic saponins on the classical pathway activation of the complement was
      higher than the activity of monodesmosidic saponins, but esterification of the
      carboxylic group of glucuronic acid in the sugar residue resulted in a
      significant decrease in anticomplementary activity.

PMID- 14661373
TI  - Freud and Jung: an incomplete encounter.
AB  - The author discusses the bases of the close, personal and professional
      relationship between Freud and Jung, and conjectures that the eventual schism
      between them was the result of the different profound psychological needs that
      each had for the other. Because of his identification with the psychoanalytic
      enquiry, particularly as it was based in large measure on his own self analysis,
      Freud looked to Jung as a collaborator who would not deviate from the principles
      at the basis of psychoanalysis, seeking psychoanalysis' acceptance within the
      established scientific community. From Jung's point of view, Freud fulfilled the
      role of a respected father figure who, Jung hoped, would grant him the autonomy
      and freedom to pursue his own scientific enquiry, based on Freud's ideas, but
      which he would revise according to his own researches. These led Jung to certain
      revisions and additions, such as the nature and function of the libido, the
      broadening of the idea of the complex (as in the Oedipus complex) to include a
      number of universal, archetypal themes, and the elaboration of the concept of the
      self. During the years of their relationship, they shared a mutual psychological
      support which was deeply important to each, based on reciprocal love and respect
      but also on a fantasy that each would be able to supply to the other a key
      capacity that the other lacked. Jung was able to offer important scientific
      verifications of a number of psychoanalytic notions via the Word Association
      Test, such as the concept of repression, of the complex, including the Oedipus
      complex, and the proof of the existence of the unconscious. However, neither
      could supply to the other what each looked for in the other at the psychological
      level. The final breakdown and rupture in their relationship was caused by their
      theoretical differences and by the fact that they became bitter competitors in a
      race to publish treatises on the nature and origins of spirituality and religion.
      It has left in its wake the implicit traces of discord and misapprehension which
      have characterized much of subsequent professional relationships between the two
      traditions.

PMID- 14661374
TI  - On defining words, some scenarios and vectors in the 'autobiography' of C. G.
      Jung.
AB  - Having first considered recent research into the circumstances surrounding the
      production and publication of the 'autobiography' of Jung, the author concludes
      that in spite of its being the work of several authors, it nevertheless
      constitutes a whole. Taken from whichever angle, they all point to Jung's
      particular inquiry into the unconscious, as it emerges through Jung's own words.
      The author goes on to suggest both a lateral and a structural reading of MDR
      (Memories, Dreams, Reflections) which in turn reveals, on the basis of the
      several dreams reported, the central 'fantasy' which inspired Jung's research and
      his oeuvre. Finally, he discusses the idea of the collective or impersonal
      unconscious and highlights the emphasis Jung places on processes which unfold
      according to rhythms which are associated with distinct scales, depending on
      whether they are those of the individual, the clan or the culture.

PMID- 14661375
TI  - Jung's very twentieth-century view of myth.
AB  - It is commonly assumed that Jung's view of myth, like his view of everything
      else, is best understood vis-a-vis Freud's. I argue that Jung in fact positions
      himself much more broadly, not merely against other psychologists of myth but
      more fundamentally against non-psychologists altogether. Undeniably, Jung pits
      his theory against Freud's, but only after pitting both his theory and Freud's
      against those theories that assume the subject matter of myth to be the external
      world rather than the human mind and that assume the function of myth to be
      either the explanation or the description of the external world rather than the
      expression of the human mind. The theorists whom Jung challenges are called
      'nature mythologists', for whom myth is either a literal explanation or a
      symbolic description of the natural world. Which element of the natural world
      myth is about varies from nature mythologist to nature mythologist. The two
      leading nature mythologists, both of whom Jung cites, were Edward Tylor and James
      Frazer. Their theories epitomize the nineteenth-century approach to myth. For
      them, myth is the 'primitive' counterpart to science, which is entirely modern.
      For them, myth and science are incompatible, science is true and myth false, and
      myth must therefore go when science comes. Jung's rejection of the external world
      as the referent of myth and of explanation or description of that world as the
      function of myth epitomizes the twentieth-century response to nineteenth-century
      theories. For not merely Jung and Freud but also twentieth-century theorists
      generally, myth is anything but the 'primitive' counterpart to modern science.
      Consequently, myth and science are not rivals, so that myth need not go when
      science comes.

PMID- 14661376
TI  - Jung's view on myth and post-modern psychology.
AB  - Post-modern psychology embodies two core themes, the social mind and the
      narrative self. Whereas the social-mind thesis seems diametrically opposed to
      Jung's position regarding human nature, the narrative-self thesis is associated
      with research and theorizing about personal myth and mythmaking in ways that
      could make contact with Jung's concerns. Jung's view is examined here with
      particular attention to McAdams' theory of narrative identity. It is suggested
      that the ostensible differences between Jung and post-modern psychology might
      reflect divergent interests, rather than necessarily irreconcilable worldviews.

PMID- 14661377
TI  - The experience of limits and the broadening of the horizons of consciousness.
AB  - The author traces the gradual evolution of the clinical and diagnostic category
      of the borderline in order to demonstrate how, in the course of a few decades,
      twentieth century psychiatric culture, with its own particular vision of the
      world, passed from an experience of limit to a concept of limit. In other words,
      as psychiatric culture became aware of a certain difficulty in defining an object
      under observation, it was gradually forced to modify its own descriptive
      categories and elaborate a new concept that contained within itself that
      primitive experience of indeterminacy. The author suggests that a similar
      phenomenon can also develop in other fields of human life, but here it takes
      place over such a long period of time that the relationship between the primitive
      experience and its subsequent conceptualization is difficult to trace. Through
      the borderline experience or the experience of limits, consciousness modifies its
      horizons, not in the sense of a simple integration of a new content but in the
      sense of a profound modification of the entire system of values in which
      consciousness identified itself up to that moment. It is in this key that the
      author attempts a psychological reading of Aeschylus' Prometheus Bound and
      Shakespeare's Hamlet, a reading that has also implications for the understanding
      of the themes emerging at present on the international scene.

PMID- 14661378
TI  - Psychoanalysis and empirical research.
AB  - At the beginning of the nineteenth century, the idea of reason began to lose its
      universal and absolute value, undermining the view of science as a form of
      objective knowledge that reveals a fundamental reality. These changes have also
      had an impact on psychoanalysis, leading to a proliferation of theories and the
      end of a positivistic approach, epitomized by a 'neutral' analyst who knows the
      contents of the patient's mind. Hermeneutic philosophy provides a tool with which
      to explore both theoretical multiplicity and the contribution of the analyst's
      subjectivity to the analytic process. Furthermore, a hermeneutic approach does
      not have to be hostile to empirical science, but can be integrated with it in a
      'scientific-hermeneutic model' in which historical and biological principles are
      given equal value.

PMID- 14661379
TI  - Psychoanalysis and Eastern spiritual healing traditions.
AB  - An exploration of the theory and practice of healing in the Eastern spiritual
      traditions reveals the centrality of the idealizing transference in the patient
      seeker's interaction with the spiritual teacher or the guru although the aim and
      development of the idealizing transference in the spiritual traditions are quite
      different from those of self psychology. In its emphasis on the guru's empathy
      and in claiming that its meditative practices radically reduce the noise and
      glare produced by the sensual self which is the chief obstacle to the teacher
      healer's empathic understanding of the patient, the Eastern healing discourse
      goes considerably beyond most traditional psychoanalytic formulations on the
      nature and communication of empathy in the analytic situation. The Eastern
      traditions' claim of a significant enhancement of the teacher-healer's empathic
      capacity through meditative practices, and its communication to the
      patient/seeker through other channels besides the verbal one, can make an
      important contribution to the discussion on the role of empathy in psychoanalytic
      discourse and, if the claim proves true, to a place for meditative practices in
      psychoanalytic education.

PMID- 14661380
TI  - 'Oh Rose, thou art sick!' Anti-individuation forces in the film American Beauty.
AB  - The film American Beauty is used as a vehicle to explore difficulties in the
      individuation process, to look at a particular aspect of couple relationships in
      which mourning is avoided, and to make a general comment about the relationship
      between film and psychological experience. The thesis of the paper is that the
      individuation process is both an intra-psychic experience and an inter-psychic
      one which relies on relationships with external figures to enable development.
      The adult couple relationship is taken as one of the key areas of emotional life
      for the individuation process and as an area that can best show up false starts,
      successes, or even retreats in psychological development. Using the poetry of
      William Blake and the work of Michael Fordham, I show a process of anti
      individuation going on in the relationship between the characters of Lester and
      Carolyn Burnham in the film.

PMID- 14661381
TI  - On innatism: a response to Hogenson.

PMID- 14661382
TI  - The degeneration of love.

PMID- 14661383
TI  - Battered woman syndrome testimony in Canada: its development and lingering
      issues.
AB  - This article examines the status of battered woman syndrome (BWS) testimony in
      Canadian courts and assesses the impact of the leading decision, Regina (R.) v.
      Lavallee. Acknowledging the test of reasonableness in criminal trials was
      constructed on a male model, the Supreme Court in Lavallee corrected the gendered
      interpretation of women in abusive relationships by admitting the BWS evidence.
      Feminist legal scholars questioned whether Lavallee had succeeded in dispelling
      the stereotypes around battered women. These concerns were partially addressed in
      R. v. Malott, but some tough issues remain: applying the reasonableness test to
      women of color and the narrow base of BWS evidence. Some directions are
      discussed: discarding BWS testimony, framing a redefined and expanded BWS
      testimony, introducing a new defense based on self-preservation, and adopting an
      alternative interpretative frame such as "coercive control." The strengthening of
      BWS testimony would call for the judges' referencing of latest empirical research
      on battered women.

PMID- 14661384
TI  - Standardized assessment of substance-related, other psychiatric, and comorbid
      disorders among probationers.
AB  - This study examined the prevalence of alcohol- and substance-related disorders in
      a random sample of 627 adult probationers in Illinois. The investigation also
      explored the prevalence of major psychiatric disorders and their co-occurrences
      with alcohol and substance use disorders. To detect the presence of psychiatric
      disorders, researchers employed standardized assessment tools based on Diagnostic
      and Statistical Manual of Mental Disorders criteria. Overall, results showed that
      probationers had significantly higher rates of psychiatric disorders, substance
      use disorders, and co-occurring disorders compared with persons in the general
      population. In light of these findings, probation administrators are urged to
      invest more resources in treating drug use, mental illness, and codisorders, the
      latter of which is associated with a higher risk of violent behaviors.

PMID- 14661385
TI  - Effect sizes in the treatment of sexual offenders.
AB  - This article considers the benefits of sexual offender treatment in terms of the
      magnitude of the effect size produced by these interventions. Comparisons are
      made of the effect sizes with those generated by treatment of other offenders, by
      treatment for mental health problems, and by treatment for physical health
      problems. In all cases, effect sizes with sexual offenders are comparable to (and
      in some cases better than) effect sizes for the treatment of the other groups. As
      a final note, it is suggested that using a harm reduction index to estimate
      effect sizes for treatment with sexual offenders would produce more meaningful
      results.

PMID- 14661386
TI  - Visual versus narrative case material: the impact on criminal psychological
      profiling.
AB  - Although some literature has emerged to examine the validity and constituent
      skills required for psychological profiling, little research has scrutinized how
      the technique works. This study examined the effects of case material on
      profiling proficiency. This was accomplished by alternating the case material
      available to participants in a profiling exercise. Groups of participants were
      presented with either a full case package, only narrative or visual case
      material, narrative material with a written description of the visual material,
      or a control condition where no case material was provided. All participants then
      completed a profiling exercise designed to measure the accuracy of their
      predictions. The results found that profiling proficiency is influenced by the
      amount of case material available, with optimal proficiency likely achieved by
      the presence of all forms of material. A trend was also observed where
      participants supplied with only the narrative case materials surpassed those with
      visual materials.

PMID- 14661387
TI  - Race and problem drug use in an English city.
AB  - The primary aim of this article is to look at the impact of drugs on the drug
      using Black population, and in doing so, the article draws comparative attention
      to drug use within the White community. The article is based on a research study
      of problem drug users registered with a London drugs project in 2000 and 2001.
      During the period of fieldwork, the vast majority of clients of the drug project
      were male, and the gap in the sex composition of the clients was more conspicuous
      in the Black group. For the sake of clarity in the use of statistical
      information, the article draws substance solely from information on the Black and
      White male clients. The findings present the Black community as a group who is
      also victimised by drugs but whose experiences of drug victimisation have often
      been undermined in the "war on drugs" rhetoric about drug trafficking.

PMID- 14661388
TI  - Terrorism and mental illness: is there a relationship?
AB  - This article examines the connections between mental illness and terrorism. Most
      social scientists have discounted a causal relationship between mental illness
      and terrorism. This is not necessarily always the case within terrorism studies,
      the media, or political circles where the psychology of terrorism is often
      expressed in the language of mentalisms, and theories of pathologisation continue
      to exist. This article reaffirms the view that apart from certain pathological
      cases, there is no causal connection between an individual's mental disorder and
      engagement in terrorist activity. The individual terrorist's motivations can be
      explained by other factors, including behavioural psychology. However, there may
      be a connection between an individual engaging in terrorist activity and
      developing a mental disorder[s]. Certain stressors that occur because of
      terrorist activity may result in psychological disturbance in terrorist
      individuals. These factors may partially explain terrorist group instability and
      should be taken into account when detaining and interrogating terrorist suspects.

PMID- 14661389
TI  - Prisoners' perception of informing to the authorities: an analysis in terms of
      functional moral judgment.
AB  - A series of functional measurement experiment show that prisoners modulate their
      moral judgments of violations of their in-group regulations. The participants
      were 67 women and 80 men, sentenced for at least three years for murder, robbery,
      drug-traffic or white collar offenses. Each was asked, individually, to imagine a
      series of incidents where incriminating information on in-group or out-group
      inmates is delivered to the prison authorities or to an ingroup source and to
      rate the deserved denigration of the informer, who was characterized as a leader
      or not and as a drug-addict or not who had a prison-leave or not. An assignment
      of approximately equal weight for social status, drug use and prison leave was
      found, beyond gender and type of offense. In line with the hypothesis of
      judgmental modularity, informing to an out-group source was judged much more
      severely than informing to in-group arbiter and than informing on an out-group
      inmate.

PMID- 14661390
TI  - Target populations, pathological biomarkers and chemopreventive agents in
      prostate cancer prevention.
AB  - Chemoprevention is the administration of agents to prevent induction of cancer,
      or to inhibit or delay its progression. In prostatic neoplasia, the time from
      tumour initiation and progression to invasive carcinoma often begins in men in
      the fourth and fifth decades of life and extends across decades. This phenomenon
      represents a unique opportunity to arrest or reverse the process of
      carcinogenesis with the use of chemopreventive agents. For prostate cancer, as
      for other cancer targets, development of successful chemopreventive strategies
      requires suitable cohorts, reliable biomarkers for evaluating chemopreventive
      efficacy and well-characterised agents. Histopathologists play an important role
      in prostate chemoprevention. In fact, they define the high-risk groups, recognise
      the surrogate end markers and evaluate the morphological effects of the agents on
      the prostate tissue specimens.

PMID- 14661391
TI  - Prostate cancer: preliminary results of a case finding campaign.
AB  - OBJECTIVES: The objective of this study was to evaluate the feasibility of
      applying a case finding programme for prostate carcinoma based on a questionnaire
      which was sent by post to the male population of a Northern Italian region.
      METHODS: In November 2000 a questionnaire containing prostate related questions
      was sent to all men aged 55 or older residing in the area served by our hospital.
      Information provided by the answers was included in a specific data base.
      Subjects considered at risk for prostate carcinoma were invited for clinical
      consultation and prostate biopsy when appropriate. RESULTS: 41,627 questionnaires
      were sent and 7,732 were completed and returned. 960 subjects (12.4%) were
      considered at risk. Presently, 816 patients have been examined and 116 were
      biopsied. Thirty-six cases of prostate cancer were found (4.4%). DISCUSSION: The
      value of mass screening programmes for prostate carcinoma is still under debate
      and mature data from controlled screening trials must be obtained before
      definitive conclusions can be drawn. In the meanwhile, considering the growing
      public awareness, it may be advisable to activate programmes asking for
      information through questionnaires about prostate disease in order to find cases
      of undetected prostate cancer.

PMID- 14661392
TI  - [Managing patients with prostate cancer in Italy during the first year after
      diagnosis. A cost description based on a sample of 8 urological wards].
AB  - OBJECTIVE: The aim of the paper is to report of an empirical retrospective study
      (1994-1999) on the cost of managing patient with prostate cancer (PC) during the
      first year after diagnosis in Italy. MATERIAL AND METHODS: In January 2000, a
      questionnaire on qualitative, quantitative and economic data concerning the
      clinical path expected for patients with PC (diagnosis; staging; follow-up; drug;
      surgery; chemotherapy and radiotherapy) was sent to 14 Italian urological wards
      (UWs), 5 school of medicine-based (Northern Italy: 2; Central Italy: 1; Southern
      Italy: 2), 4 self-governing hospital-based (Northern Italy: 1; Southern Italy:
      3), 5 Health Authorities hospital-based (Northern Italy: 2; Central Italy: 2;
      Southern Italy: 1). UWs were expected to contribute to analysis with 15 patients'
      records per year each, for a total amount of 1.260 filled questionnaires. Only
      medical costs related to patient management have been considered; hospitals and
      Health Authorities overheads were not taken into account. A cost description was
      performed considering the hospital viewpoint. RESULTS: We received 416 out of
      1.260 expected questionnaires (redemption rate: 33%) from 8 out of 14 UWs: 2
      school of medicine-based (Central Italy: 1; Southern Italy: 1); 2 self-governing
      hospital-based (Southern Italy: 2); 4 Health Authorities hospital-based (Northern
      Italy: 1; Central Italy: 3). Only 411 out of 416 questionnaires were included in
      data analysis. Patients' average age at the time of diagnosis was 74.1 years
      (range: 68.6-76.7). A moderate percentage of neoplasms in patients' relatives was
      reported (17.8%; 5.6% for PC). The average cost per patient with CP during the
      first year after diagnosis was Euro 6,575.31 (range: Euro 5,035.65-Euro
      12,367.69). The cost-driver was drug therapy (43.07%), followed by surgery
      (26.41%), diagnosis (12.39%), staging (8.58%); follow-up (8.25%) and radiotherapy
      (1.30%); no data on chemotherapy was reported. Diagnosis, staging and follow-up
      tests and procedures were performed mainly in outpatient setting (81.84% 53.30%
      and 94.72%, respectively) and requested by hospital urologists (70.26%; 52.88%
      and 67.95%, respectively). Total PSA was the most frequent test for diagnosis
      (503 out of 2,047 procedures) and follow-up (782 out of 3,351 procedures), as
      well as bone scan was for staging (337 out of 1,023 procedures). As far as drug
      therapy is concerned, LHRH-analogue was the most prescribed drug (227 patients).
      Surgery (lymphoadenectomy: 9; orchidectomy: 20; urinary outlet dysobstruction:
      51; prostatectomy: 104) was performed in 179 patients; 5 out of 179 patients
      underwent more than one surgical intervention. Radiotherapy (338 sessions) was
      undertaken in 15 out of 411 patients. CONCLUSIONS: Cost of managing patient with
      PC during the first year after diagnosis in Italy could be reduced by increasing
      outpatient procedures and decreasing post-surgery hospital stay. Our research may
      hopefully foster further empirical studies on the health economics of PC in our
      country.

PMID- 14661393
TI  - [Extracorporeal shock wave lithotripsy as surgical therapy in the kidney-ureter
      calculosis].
AB  - INTRODUCTION: The coming of the extra-corporeal shock waves lithotripsy (ESWL)
      represented one of the main progress in medicine of all times. MATERIALS AND
      METHODS: From January '84 up to March '99, 7.508 patients underwent
      extracorporeal shock wave lithotripsy (ESWL) for renal, ureteral and bladder
      stones with a total of 13.032 treatments. 6.329 kidney stones, 2.165 ureteral
      calculosis and 52 bladder stones, for a total amount of 8.546 stones were
      treated. Seven different lithotripters have been used: radiologic-based Dornier
      HM3 with electrohydraulic shock waves production, radiologic-based modified
      Dornier HM3 with electrohydraulic shock waves production, ultrasonography-based
      Dornier MPL 9000 with electrohydraulic shock waves production, ultrasonography
      based EDAP LT 01 with piezoelectric shock waves production, ultrasonography and
      radiologic-based EDAP LT 02 with piezoelectric shock waves production,
      ultrasonography-based Piezolith 2200 and the Piezolith 2300 only with
      piezoelectric shock waves production. In 1,451 patients an auxiliary action was
      necessary. RESULTS: Only a treatment was sufficient in 5.337 patients (77.7%),
      two in 1.497, three in 507 patients, four in 248 patients, five in 109, six in
      55, seven in 34, eight in 9, nine in 12, ten in 5, eleven in a patient, twelve in
      a patient, thirteen in a patient, fourteen in two patients and fifteen in a
      patient. The patients who had a negative abdomen radiograph or ultrasound after
      two months were considered "stone-free". We have considered urolithies smaller
      than 3 mm as fragments, with the possibility of natural expulsion, non
      conditioning lying behind. Totally the results was: 5.950 patients "stone-free",
      753 patients with fragments, 257 patients with non-broken calculi and 547
      patients with dust only. The "stainstrasse" with spontaneous resolution and the
      one with instrumental resolution, the hyperpyrexia, the serious colics, the
      symptomatic renal haematomas and the intolerance to the treatment (vomiting and
      nausea) have been considered as complications. CONCLUSIONS: Nowadays, except for
      the cases in which are necessary admission to hospital and urgency treatment,
      since imminent colics are present, the ESWL may be performed in day-hospital.
      Since the first years of employment the ESWL has solved almost all the cases of
      urolithiasis. Nevertheless the experience has proved the extreme aggressiveness
      and inappropriate characteristics of a number sometimes too high of re
      treatments. The ESWL should maintain the feature of non-spread methodic when it
      is possible to use it in cases solving with two--maximum three--treatments.

PMID- 14661395
TI  - Paraurethral leiomyoma.
AB  - A case of a asymptomatic paraurethral leiomyoma in a young female patient is
      presented. Paraurethral leiomyoma is a benign hormone-dependent tumor of
      mesenchymal origin. Up today only 7 true paraurethral leiomyomas have been
      reported in the literature. The tumor can be asymptomatic, but can cause dysuria,
      urinary frequency, urinary retention and dispareunia. simple excision is usually
      the adequate treatment.

PMID- 14661394
TI  - [Lithiasis in complete ureteral duplication and prostate cancer: combined surgery
      treatment].
AB  - The diagnosis of congenital anomalies of the urogenital tract in the adult is
      uncommon. Complete ureteral duplication represents a congenital anomaly of the
      ureters, usually draining a duplex kidney, with a second orifice entering the
      bladder, urethra or other structures. In the majority of cases, this pathology is
      completely asymptomatic; sometimes it's diagnosed because of complications such
      as infections, hydronephrosis, lithiasis, or in the evaluation of the urinary
      tract. Early diagnosis of localized prostatic adenocarcinoma is increased due to
      worldwide use of PSA screening and the optimization of multiple biopsy,
      increasing radical surgery treatments. The association between these two
      pathologies is a rare event. We present the case of a 69-years old man diagnosed
      for localized prostatic cancer and bilateral complete ureteral duplication,
      megaureter and stenosis of left superior ureteral meatus, leading in the
      prostatic urethra. Terminal ureter with the ectopic meatus opening in prostatic
      urethra was occupied by stones. A combined surgical procedure was undertaken:
      radical prostatectomy, ectopic ureter section, lithiasis removal and
      reimplantation of left ectopic ureter into the bladder. There is no case
      described of the association of this urogenital anomaly and prostate cancer and
      the combined management of both.

PMID- 14661396
TI  - A rare case of benign fibroepithelial tumor of the seminal vesicle.
AB  - Primary tumors of seminal vesicles are rare. We report on a benign tumor of the
      seminal vesicle with fibroepithelial and cystic features. We performed a
      laparoscopic transperitoneal approach. The mass, not fixed to any anatomical
      structures except to the prostate, was isolated and removed. Histological
      examination of tumor revealed two distinct components: epithelial and stromal. We
      consider the term fibroadenoma more appropriate than cystoadenoma, because the
      stroma is not reactive but a distinct neoplastic component.

PMID- 14661397
TI  - [Mediterranean diet, micronutrients and prostate carcinoma: a rationale approach
      to primary prevention of prostate cancer].
AB  - Cancer of the prostate is one of the most commonly diagnosed solid malignancies
      and the fourth leading cause of cancer-related deaths in men living in Italy.
      With an ageing population, the number of men living with early stages of prostate
      cancer is expected to increase. There is an impelling need to prevent the onset
      of the cancer or delay the progression of carcinogenesis in this organ. The
      chemoprevention of cancer is a relatively new concept defined as the
      administration of pharmacological agents (drug or diet-derived supplements) to
      prevent, delay or reverse the carcinogenesis. Epidemiological data showing ethnic
      and geographic variations in the incidence of, and mortality from, prostate
      cancer have suggested that the consumption of dietary factors may be protective.
      There is increasing evidence that diet (particularly dietary fat intake) may play
      a significant role in early prostate carcinogenesis. Dietary micronutrients and
      antioxidants are under intense scrutiny. These factors include the vitamin D and
      E, lycopene, selenium, zinc, poliphenols, isoflavonoids, and phytoestrogens
      (especially soy products and green tea). The old Mediterranean diet (based on
      cereals, vegetables, polyunsaturated fats, fruits, fish and low quantities of
      dairy products and meat) is now sparingly adopted because of the globalisation of
      the food chain which now involves also our country. Nevertheless, our traditional
      dietary habits are considered of great value in the prevention of cardiovascular
      or cancerous diseases and particularly of prostate cancer.

PMID- 14661398
TI  - The uninsured patient.

PMID- 14661399
TI  - Happy birthday. 30 years after their inception, the Area Health Education Centers
      are alive and well.

PMID- 14661400
TI  - Controlling pain in the elderly: careful treatment can prevent suffering, improve
      quality of life.

PMID- 14661401
TI  - Free flap coverage of scalp defects following radiation.

PMID- 14661405
TI  - Looking back: tracheotomy for membranous croup (death on the fourth day from
      pneumonia). 1885.

PMID- 14661404
TI  - The insurance meltdown.

PMID- 14661403
TI  - Stimulant therapy in attention deficit/hyperactivity disorder.
AB  - Stimulant medication is a significant part of the multimodal management of
      children with ADHD. The primary care physician should coordinate the assessment
      and treatment of the child with this disorder. Understanding the use of stimulant
      medications and a thorough understanding of the challenges facing family,
      patients, educators and health planners is necessary in order to address issues
      related to the complexities of ADHD.

PMID- 14661402
TI  - Posterior reversible encephalopathy syndrome: an overview.

PMID- 14661406
TI  - [Prognostic evaluations of the medical and demographic processes].
AB  - The medical-and-demographic processes as a starting point for the planning of
      means and resources for the short- and average-term future are forecasted in the
      paper on the basis of long-term peculiarities of the natural-science data and
      with respect for the social-and-economic crisis now underway in the country.

PMID- 14661407
TI  - [Medical-demographic and social-economic aspects in the emergence of families
      with few children].
AB  - A 10-year prospective study was undertaken of a category of 957 families, who
      emerged in 1990-1992, for the purpose of defining the factors influencing the
      shaping of few-children families: 276 (28.8%) of them had few children, 558
      (58.4%), had an average number of children and 123 (12.8%) had many children
      during the mentioned time span. According to the results, a set of factors was
      defined accountable for few-children families with the key of them being:
      duration of education (34.1 and 40.2% for female and male, respectively);
      marriage age exceeding 25 years (47.1 and 51.1%); an unsatisfactory health state
      of marital partners and of their children, a high rate of divorces ((40.6%); poor
      material and dwelling conditions (69.6%); a low standard of social protection
      etc.

PMID- 14661408
TI  - [The influence of some medical and social factors on the reproductive health of
      women].
AB  - Some of the social-and-hygienic factors that affect the female reproductive
      health and their reproductive abilities were investigated. The offered case study
      belongs to a series of research dealing with the reproductive heath with respect
      to changing social-and-economic conditions. According to an analysis of the
      obtained data, the smallest quantity of healthy women were at an age of up to 20
      (33.3%). 62.5% of women, who visited their gynecologists infrequently (less than
      once in a year), had chronic pathologies. A majority of women with chronic
      pathologies in the reproductive system had higher and special education; besides,
      they were occupied under hazardous conditions, their dwellings were
      unsatisfactory, they were not married, they started their sexual experience at an
      age below 18, and their sex partners were not regular; finally, the abortion rate
      was high among them. Thus, a stable orientation towards a few-children family
      developed in such women.

PMID- 14661409
TI  - [Role of the family in shaping the health behavior of an adolescent].
AB  - Sponsored by the Committee for Healthcare of the City of Moscow, we conducted an
      anonymous, cross, educational questioning of 250 families of teenage
      schoolchildren (in Moscow), who used to have sexually transmitted infections
      (STI), and a questioning of teenage-schoolchildren without the STI history
      (controls). The questioning program of teenagers and of their parents was split
      into 5 units based on 3 basic components covering the health state of any
      population category, i.e. body, environment, behavior. Our conclusion was that
      the communication of children with their parents enables the children to master
      the basic norms of behavior and morality and to observe the implementation of
      role-tied functions in the parental family. Therefore, it is advisable to focus
      on the parents and families while working out the purpose-oriented comprehensive
      programs of disease prevention (STI, in particular) among children and teenagers.

PMID- 14661410
TI  - [The influence of being an orphan on the physical development of children].
AB  - The physical development of 183 inmates of Voronezh Children's Home, aged 1 month
      to 4 years, was studied. The results showed lower parameters of their physical
      development versus the regional standards. The conclusion is that adoption is the
      best solution in case of orphans. Besides, making the families healthier in the
      social way, as well as prevention of undesired pregnancies and of giving birth to
      the deliberately unhealthy offspring conceived from alcohol- and drug-addicts are
      extra weighty factors.

PMID- 14661411
TI  - [Disability due to cardiovascular diseases].
AB  - Extension of the time limits of temporary disability (TD) is an important method
      in preventing the disablement due to the key cardiac-and-vascular pathologies.
      Thus, the extension of TD term for patients with favorable clinical and labor
      prognostications and realization, during the same time period, of active all
      possible therapeutic-and-recovery measures enabled a majority of such patients to
      catch up with their ability to work and to resume their former occupations.

PMID- 14661412
TI  - [Life expectancy of the residents of St. Petersburg].
AB  - The dynamics of the mean life expectancy (LE) were analyzed for the residents of
      Saint-Petersburg in 1979-2001. The trends of the above index were compared for
      Saint-Petersburg, Russia and a number of countries in the Eastern, Central and
      Western Europe. The influence of different age- and sex-groups on the mortality
      intensity changes observed at crucial stage of the mentioned period were analyzed
      and evaluated. An LE increase at removing certain mortality causes from some age
      intervals were assessed. The specificity of mortality processes in Russia and
      Saint Petersburg was found to be essentially different from that observed in
      other countries. The conclusion was substantiated on that the social-and-economic
      situation in the country and in the city has a significant impact on the
      mortality level among population and, primarily, among the able-bodied
      population.

PMID- 14661413
TI  - [Issues of biological safety].

PMID- 14661414
TI  - [The system of state purchases for medical services in the Republic of
      Kazakhstan].
AB  - Described in the paper is the normative-and-legal system for the state purchases
      of medical services in the Republic of Kazakhstan.

PMID- 14661415
TI  - [Promoting the efficient functioning of an ophthalmologic hospital].
AB  - A model of hospital management, i.e. a state regional ophthalmologic clinic, was
      designed on the basis of the Republican Clinical Hospital for Ophthalmology of
      the Udmurt Ministry of Health. Apart from the basic typical elements, its
      structure comprises the research-and-production units (as finances sources) and
      investment technologies. Described in the paper are related components and an
      analysis of the medical-and-economic efficiency of using the above model.

PMID- 14661416
TI  - [A comparative description of the formation of population's demand for medical
      care].
AB  - One hundred and twenty seven patients of 24-hour and day-time patient-care
      facilities (Stavropol Region) were questioned. Problematic situations were
      denoted in the medical-care system, which are related with a shaping demand for
      medical care rendered to patients under such service conditions.

PMID- 14661417
TI  - [Analysis of morbidity among the residents of Chelyabinsk].
AB  - Presented are the results of an analysis of the general morbidity based on
      residents' asking for medical care at the patient-care facilities in the
      Chelyabinsk Region during 1991-2001.

PMID- 14661418
TI  - [A sociological evaluation of medical care measures in craniocerebral trauma].
AB  - According to a questionnaire of 830 patients and 153 neurologists, both a timely
      asking for medical care and a timely treatment at specialized neurology hospitals
      are the key factor that cuts the rate of complications in craniocerebral trauma.
      Finally, a differential approach to treatment schemes with due respect to a
      trauma severity, availability of rehabilitation centers and application of new
      medical technologies, e.g. cranio-sacral therapy, are equally important.

PMID- 14661419
TI  - [Standardization and its importance in rendering medical care to patients with
      cancer of the bladder].
AB  - There are only as many as 31 specialized oncourological departments in 24 of 89
      (27%) Federation Subjects in the Russian Federation that can render the
      oncourological care at the municipal and federal levels. As for other remaining
      65 (73%) Subjects, the urologists are preoccupied with diagnosis and treatment of
      urinary-bladder cancer in them. Russian patient-care facilities have presently
      differing opportunities in the sphere of diagnosis and treatment of the mentioned
      pathology. Their related outfit for this purpose is on the whole unsatisfactory.
      An optimal management of medical care rendered to the discussed category of
      patients and targeted at promoting its quality and efficiency is possible only on
      the basis of standardization of diagnostic and treatment approaches. The stage
      nature of medical care rendered to such patients is closely related the
      standardization issues. An accurate definition of stages and of patient-care
      facilities, which would be in charge for the above stages, would, in the end,
      clearly depict a sequence of steps for the diagnostic-and-therapeutic schemes
      applicable to patients with cancer of the urinary bladder. This, in its turn,
      would optimize the diagnostic-and-therapeutic process and outline the priority
      spheres in healthcare financing.

PMID- 14661420
TI  - [Experience of patient-care facilities in the Voronezh Region in advancing the
      medical care standards].

PMID- 14661421
TI  - [Training of physicians-to-be in the field of HIV infection].

PMID- 14661422
TI  - [Issues related to expertise in the quality of medical care].

PMID- 14661423
TI  - [Reforming of the health care system in Uzbekistan].

PMID- 14661425
TI  - The social impact of medicine. Chapter 12.

PMID- 14661424
TI  - A snapshot of tobacco-related messages relayed in pediatric offices in Delaware.
AB  - OBJECTIVE: Much research exists demonstrating that pediatricians should counsel
      patients and families about tobacco. However, few data are available about
      tobacco-related messages relayed in pediatric offices. Since an anti-tobacco
      office environment can be a strong component of an active tobacco prevention
      program, we evaluated pediatric offices in Delaware to characterize tobacco
      related messages. METHODS: A convenience sample of 32 of 63 (51%) pediatric
      offices in Delaware was directly evaluated for the presence of tobacco-related
      messages. Fifty-five of 63 (87%) pediatric practices in Delaware were contacted
      by telephone to inquire about the presence of a tobacco coordinator. RESULTS: The
      32 practices represented 71 physicians, were located in all three counties
      throughout the state, and were urban and non-urban in setting. The same
      investigator evaluated practices in a single site visit. All were located in
      smoke-free buildings. At one office, people were seen smoking outside; however,
      the presence of discarded cigarettes was much more common. Thirteen practices
      (41%) employed smokers, most of whom smoked outside during work hours. Twenty-one
      of 28 practices (75%) had waiting room magazines containing tobacco
      advertisements. Fifteen practices (47%) offered anti-tobacco literature while six
      practices (19%) displayed visual media, none exclusively addressing tobacco. Nine
      practices (28%) use chart flags to identify smokers. None of 55 pediatric
      practices in Delaware contacted by telephone identified an office tobacco
      prevention coordinator. CONCLUSIONS: Our data indicate that, in Delaware, the
      pediatric offices we visited overall convey a limited message about tobacco and
      could strengthen tobacco prevention strategies. Research measuring the impact of
      office-based anti-tobacco messages is needed. If these messages are effective in
      preventing tobacco use, practitioners can supplement active counseling with
      indirect interventions that require minimal maintenance once established and that
      place no additional demands on their time.

PMID- 14661426
TI  - The med.pro domain.
AB  - The evolution of the Internet Domain Name System is summarized. The credentialing
      requirements with respect to licensure, board certification, and affiliations for
      obtaining a med.pro address are described. Security issues are discussed, and the
      mechanisms for obtaining a med.pro are delineated. The relative advantages and
      disadvantages of the med.pro domain are presented.

PMID- 14661427
TI  - Powered endoscopic removal of a maxillary sinus cyst.

PMID- 14661428
TI  - Bilateral ventricular Webs.

PMID- 14661429
TI  - Facial nerve hemangioma.

PMID- 14661430
TI  - Postswallow aspiration secondary to stenosis of the upper esophageal sphincter.

PMID- 14661431
TI  - Patient report call-back sheets.

PMID- 14661432
TI  - Larynx amyloidosis.

PMID- 14661433
TI  - ENG in a patient with Meniere's syndrome and evidence of vestibular recruitment.

PMID- 14661434
TI  - Glandular tularemia in a Native American child.
AB  - This case report details the clinical manifestation and course of glandular
      tularemia, an uncommon but significant cause of cervical lymphadenopathy in
      children. We discuss the unique attributes of this disease along with appropriate
      steps that lead to early identification of the organism and effective treatment.
      The potential use of the organism as a bioterrorism agent is another interesting
      aspect of this entity.

PMID- 14661435
TI  - Hyperhomocysteinemia and left internal jugular vein thrombosis with Meniere's
      symptom complex.
AB  - The author describes the case of a 68-year-old woman who experienced severe
      symptoms of Meniere's syndrome. Ultrasonography of the neck detected a clot in
      the left internal jugular vein. The patient was hospitalized and anticoagulated,
      and her symptoms soon resolved. The author speculates that the clot-induced
      hemodynamic changes led to venous insufficiency in the vein of the paravestibular
      canaliculus and ultimately caused the patient's symptoms. The blood work-up
      revealed that the patient had an elevated fasting homocysteine level, which is a
      known risk factor for thrombus formation.

PMID- 14661436
TI  - Recurrent malignant schwannoma of the parapharyngeal space in neurofibromatosis
      type 1.
AB  - Malignant schwannoma is an aggressive tumor that carries a poor prognosis despite
      wide excision, chemotherapy, and radiotherapy. Malignant schwannoma of the
      parapharyngeal space is an uncommon finding; to our knowledge, only four cases
      have been described in the literature during the past 30 years, and only one of
      them involved a patient who had clinical evidence of neurofibromatosis type 1. In
      this article, we describe a new case of malignant schwannoma of the
      parapharyngeal space in a patient who had clinical evidence of neurofibromatosis
      type 1. Following resection of the tumor and a total parotidectomy, the diagnosis
      was made on the basis of histology and immunohistochemistry. The patient
      underwent postoperative chemotherapy with carboplatin and UP16. However, 5 months
      following surgery, the tumor recurred and metastasized. The patient was then
      placed on a different polychemotherapeutic regimen, which was made up of 3 g/m2
      of ifosfamide, 1.5 mg/m2 of vincristine, and 1.5 mg/m2 of doxorubicin (IVA2
      protocol). The IVA2 regimen slowed tumor growth, but 13 months after the
      initiation of therapy, the patient died of neoplastic cachexia. Although
      chemotherapy is generally ineffective in most cases of malignant schwannoma, we
      did experience some positive results with the IVA2 protocol. Therefore, we
      recommend that this combination be considered as a first-line adjuvant therapy
      following surgery or as a first-line therapy for patients with inoperable tumors.

PMID- 14661437
TI  - Expression of EphB4 in head and neck squamous cell carcinoma.
AB  - EphB4 is a receptor tyrosine kinase that is expressed on epithelial cells during
      fetal life. It is also expressed on some venous endothelial cells. We conducted a
      study of six men with primary squamous cell carcinoma of the head and neck
      (HNSCC) that had metastasized to the cervical lymph nodes. Our goal was to
      determine if EphB4 is aberrantly expressed in cases of HNSCC and to determine if
      there is a qualitative difference between the expression of EphB4 on primary and
      metastatic tumors and its expression on normal mucosa adjacent to primary tumors.
      From each patient, we obtained specimens of the primary tumor, the nodal
      metastasis, and the adjacent normal mucosa, and we performed immunocytochemistry
      on each. We observed EphB4 expression in all primary and metastatic tumors and no
      expression in the normal tissue. In each of the six patients, expression was
      greater in the metastatic tumor than in the primary tumor. We conclude that EphB4
      is a novel target in the treatment of HNSCC.

PMID- 14661438
TI  - Ectopic subglottic thymic cyst: a rare cause of congenital stridor.
AB  - We describe the case of a 10-day-old boy who was brought to the hospital with
      stridor and respiratory distress. He was diagnosed with stenosis caused by a
      subglottic cyst. After the cyst was removed endoscopically, the patient's
      symptoms resolved. Pathology identified the cyst as ectopic thymic tissue. This
      case is noteworthy because we believe it represents the first reported instance
      of ectopic thymic tissue in the subglottis.

PMID- 14661439
TI  - Malacoplakia manifesting as a chronic inflammatory mass at the site of a
      nonhealing surgical wound.
AB  - Malacoplakia in the head and neck is uncommon, and malacoplakic lesions involving
      the thyroid are extremely rare. The author describes the case of a 64-year-old
      woman who developed malacoplakia at the site of a previous total thyroidectomy.
      The disease manifested as a chronic inflammatory mass beneath a persistently
      discharging surgical wound site, and it prevented the incision from healing.
      Diagnosis was based on a thorough histopathologic analysis.

PMID- 14661440
TI  - Improved immunotherapy with a rapid allergen vaccination schedule: a study of 137
      patients.
AB  - Rapid allergen vaccination (RAV) is the updated term for what was previously
      called rush immunotherapy and rapid desensitization. RAV offers several
      advantages over traditional immunotherapy--that is, conventional allergen
      vaccination (CAV)--in terms of faster efficacy, better compliance, and cost
      effectiveness. We used a 3-hour RAV protocol to treat 137 allergy patients. All
      patients were premedicated with either prednisone or prednisolone and an H1
      antihistamine. Following the RAV procedure, all patients resumed a CAV schedule.
      Only six patients (4.4%) experienced a mild systemic reaction to RAV, and five
      (3.6%) experienced a mild systemic reaction to CAV 14 to 77 days later. All six
      patients who reacted to RAV quickly responded to treatment--in most cases,
      subcutaneous epinephrine and/or nebulized albuterol--and were sent home after a
      short period of observation. Compliance rates at 3, 6, and 12 months were 96.4,
      94.2, and 75.9%, respectively, which is an improvement over rates previously
      reported for patients undergoing CAV therapy. We conclude that the 3-hour RAV
      protocol can be safely and successfully administered. Patients who undergo RAV
      are more compliant with their subsequent CAV regimen than are patients who do not
      undergo RAV because signs of clinical efficacy manifest almost immediately and
      because RAV is associated with substantially lower rates of systemic reactions.
      Moreover, RAV is associated with less morbidity and less expense. Our findings
      should encourage physicians who treat allergy patients to give further
      consideration to using RAV.

PMID- 14661441
TI  - Protecting privacy in the behavioral genetics era.

PMID- 14661442
TI  - [Transfusion problems in surgery and anesthesiology. The causes, consequences,
      prevention and treatment of perioperative anemia].
AB  - INTRODUCTION: The classical indication for blood transfusion is the correction of
      oxygen delivery failure, and the elimination of tissue ischaemia. Such
      indications in the surgical and anesthesiological practice are the acute
      haemorrhagic states (trauma, acute gastrointestinal bleeding, intraoperative
      hemorrhage), as well as diseases associated with chronic blood loss (occult
      bleeding caused by malignancies, and ulcerating processes etc.). The traditional
      surgical and anesthesiological viewpoint has adopted a remarkably liberal
      approach to the indication of blood transfusion, and a whole range of its subtle,
      medium-long term adverse effects has been taken into account only recently. The
      purpose of this review was to analyze the causes and pathophysiological
      consequences of perioperative anemia and blood loss, as well as to reconsider the
      proper indications of blood transfusion in the view of immunological sequela. The
      most recent data on the transfusion related immuno-depression and
      immunomodulation are summarized. The authors wish to provide clues for the
      definition of "transfusion trigger", in addition, methods available for the
      clinical practice to reduce blood demand and to restore oxygen transport capacity
      during surgical and anesthesiological interventions are revisited. Based on the
      review of the literature and the personal experience of the authors the practical
      recommendations concerning the administration of blood and blood products should
      be summarized as follows: 1. Blood transfusion is rarely indicated if the
      hemoglobin level is above 10 g/dl, and in fact always necessary if it is less
      than 6 g/dl, especially, if the anemia developed acutely. 2. The "transfusion
      trigger" is subject to continued debate, and whether a particular patient with
      intermediary (6-10 g/dl) Hb levels should be transfused or not must be assessed
      in the perspective of the potential complications initiated by the inadequate
      oxygenation. 3. If major co-morbidity (e.g. emphysema, ischaemic heart disease)
      is present, 10 g/dl Hb, in case of respirator dependency 12 g/dl Hb levels
      justify the administration of transfusion. If feasible, the beneficial effects of
      allogenous blood sparing methodologies should be utilized. CONCLUSIONS: Although
      the National Blood Supply Service is excellently organized in Hungary, the
      current clinical practice is not satisfactory. The use of up-to-date methods at
      the average surgical departments is suboptimal, and due to the lack of knowledge
      concerning the recent advances in immunology the clinicians are far too liberal
      in the indication of blood transfusion. The objective is to establish a modern
      surgical and anesthesiological transfusion practice based on the solid
      understanding of immunological facts, and to modernize the continued education,
      as well as to improve the financing of costly blood saving methodologies.

PMID- 14661443
TI  - [Meropenem therapy in children with febrile neutropenia].
AB  - OBJECTIVES: Infectious complications are the major causes of morbidity and
      mortality in children receiving chemotherapy for malignant diseases.
      Granulocytopenia carries the risk of bacterial infection, and also, if prolonged,
      of fungal infection. The aim of this study was to evaluate the clinical
      effectiveness of meropenem in immunocompromised children in association with
      isolated bacteria from blood cultures and clinical background. METHODS:
      Retrospective study of all febrile episodes when meropenem was used in
      neutropenic children between January 1998 and December 2002 in the haemato
      oncological units of the authors hospital. During the study period meropenem was
      used in 87 febrile events diagnosed in 55 patients (mean age 10 years 5 months),
      and 328 bacterial cultures were performed. Blood samples were taken from each
      patient with granulocytopenia (< 0.5 G/l) and fever (> or = 38 degrees C), prior
      to the start of any antibiotic therapy. For the microbiological process Bactec
      9050 (Becton Dickinson) blood culture systems were used. RESULTS: Microorganisms
      were detected and identified in 64 (19.5%) from the 328 hemocultures. There was a
      predominance of Gram-positive strains, 67% (43/64)--the most common bacteria
      being coagulase negative Staphylococcus (cnS). From the 87 periods in 43 cases
      (49.4%) the infection was documented microbiologically. In 16 additional cases
      the infection was proven clinically (based on the clinical course, laboratory and
      radiologic results) and 32.2% (28/87) of the febrile neutropenic episodes were
      considered to be fever of unknown origin. Meropenem was used in a mean dose of
      60.8 (30-120) mg/kg/die, for 9.3 (2-24) days. The success rate of the meropenem
      therapy -excluding the proven fungal (n = 13) or cnS (n = 15) infections-was
      72.9%. No severe side effects occurred in any regimens. CONCLUSION: The results
      demonstrate that meropenem is effective and well-tolerated when used for the
      treatment of feverish neutropenic cancer children.

PMID- 14661444
TI  - [Macroprolactinemia in the differential diagnosis of hyperprolactinemia].
AB  - INTRODUCTION: Biologically active prolactin and the inactive fraction of
      macroprolactin can be present in hyperprolactinaemic sera. The reaction of
      routinely used prolactin assays with macroprolactin is variable. AIMS: The
      present study was undertaken to analyse the leading clinical signs of
      hyperprolactinemia in macroprolactinemia and true hyperprolactinemia and to
      assess the prevalence of macroprolactinemia in hyperprolactinemic females.
      METHODS: 1571 consecutive female patients were investigated for
      hyperprolactinemia. Prolactin was measured before and after precipitation of
      macroprolactin by polyethylene glycol in 285 hyperprolactinemic (> 520 mlU/l)
      patients. Since not a single case of macroprolactinemia (recovery < 40%) was
      found in the range of 520-700 mlU/l, only in women with prolactin > 700 mlU/l (N
      = 254) entered the study. RESULTS: In 59 patients (23%) macroprolactinemia was
      found. In women, the occurrence of macroprolactinemia increased with advancing
      age (p < 0.05). "A priori" clinical signs indicating hyperprolactinemia occurred
      less frequently in patients with macroprolactinemia than in those with true
      hyperprolactinemia. Pituitary microadenoma was found in 9.8% of
      macroprolactinemia vs. 31.6% in true hyperprolactinemia (p < 0.01); galactorrhea:
      4% in macroprolactinemia vs. 19% in true hyperprolactinemia, (p < 0.05);
      infertility: 17% in macroprolactinemia vs. 44% in true hyperprolactinemia (p <
      0.05). In 8 out of 59 women with macroprolactinemia, true hyperprolactinemia
      appeared simultaneously (15.3%). Occurrence of polycystic ovaries syndrome was
      more frequent in the true hyperprolactinemia (12%) that in macroprolactinemia
      (4.5%). CONCLUSIONS: It has been shown that macroprolactin does not occur in mild
      hyperprolactinemia. In women, the occurrence of macroprolactinemia increases with
      age. "A priori" clinical signs indicating hyperprolactinemia and pituitary
      abnormality are less frequent in macroprolactinemia than in true
      hyperprolactinemia. The diagnosis of macroprolactinemia should be used only, when
      the PRL levels fall to the normal range after precipitation. To avoid diagnostic
      and therapeutic pitfalls the screening for macroprolactin of all patients with
      prolactin > 700 mlU/L is recommended.

PMID- 14661446
TI  - [Extent of agreement in case of complete identity].
AB  - Two diagnostic procedures with binary outcomes are usually compared by Cohen's
      kappa coefficient of agreement. If the results of the two procedures are
      completely identical on a sample and so kappa equals to 1, the precision of the
      estimate can not be computed with the usual formulae and statistical softwares. A
      formula for variance which is valid in this particular case is presented together
      with a real example.

PMID- 14661445
TI  - [Hand-arm vibration syndrome in foundry workers].
AB  - INTRODUCTION: The hand-arm vibration syndrome of the foundry workers using
      chipping hammers and grinders were analysed in Hungary last in 1950th-s years.
      Therefore it seemed necessary to consider the present situation of the disease.
      AIM: To study of the signs of the hand-arm vibration syndrome of the foundry
      workers using chipping hammers and grinders. METHOD: Retrospective analysis of
      the clinical findings of 154 foundry workers using chipping hammers and grinders.
      The examination included the vascular, neurological and musculoskeletal systems
      of the upper extremities in 95 patients. RESULTS: The first symptoms referring to
      hand-arm vibration syndrome appeared on the average after seven years exposure.
      The signs of the 95 patients were as follows: vascular disorders: 75 cases
      (78.9%), peripheral neurologic lesion: 62 cases (65.3%), osteoarticular damage:
      35 patients (36.8%). The Raynaud's phenomenon developed more commonly on the left
      than the right hand. The rate of the improvement of the Raynaud's phenomenon on
      the average 6.5 years after the cessation of the exposure on the basis of the
      result of the cold provocation test was 32.8%. Lesion of the peripheral nerves of
      the upper limbs, mostly of distal type was experienced in 41, whereas tunnel
      syndromes of the upper extremities in 21 cases. The most common amongst the
      latter (18 cases) was the thoracic outlet syndrome. Osteoporosis of the carpal
      bones was detected in 36 patients (37.9%), but osteoarthrosis of the joints of
      the upper limbs in 12 cases (12.6%). There was no aseptic necrosis of the bones.
      Fatigue fracture of the spinous process of the cervical VII vertebra occurred in
      one single case. CONCLUSIONS: Using chipping hammers and grinders in foundry is
      one of the most dangerous hand-arm vibration exposure in Hungary. The most
      frequent signs are the vascular and neurological lesions. Due to relatively rare
      occurrence of osteoarticular damages X-ray examinations are not necessary during
      periodical medical follow up. The most effective possibility of the prevention is
      the diminishing of the daily exposure time.

PMID- 14661447
TI  - [Treatment of colorectal carcinoma].

PMID- 14661448
TI  - [Summary of 3rd Chinese International Congress on Oral and Maxillofacial Surgery
      in conjunction with 6th National Congress on Oral and Maxillofacial Surgery].

PMID- 14661449
TI  - [Cephalometry study of craniofacial and upper airway in boys with OSAS].
AB  - OBJECTIVE: The purpose of the study was to find out craniofacial and upper airway
      characteristics of boys with OSAS. METHODS: Craniofacial and upper airway
      morphology was studied by computerized cephalometric analysis in 7 mixed
      dentition boys with OSAS and 29 healthy boys. RESULTS: The main differences of
      OSAS patients were shown as follows: longer dimension of cranial base with
      clockwise rotation of palate plane and mandibular plane, increased height of the
      tongue, inferiorly displaced hyoid bone, decreased sagittal dimension of upper
      airway in soft palate level and tongue base level. In addition, the tongue and
      soft palate occupied a larger portion of the oropharyngeal area. CONCLUSION:
      Patients with OSAS presented multiple abnormalities in craniofacial and upper
      airway. Cephalometry can be useful in diagnosis and determining the appropriate
      treatment for OSAS patients.

PMID- 14661450
TI  - [Clinical evaluation of tunnel-restoration].
AB  - OBJECTIVE: To evaluate the clinical effect of tunnel-restoration. METHODS: 35
      teeth with pulpitis or periapical periodontitis caused by interproximal caries
      were selected. Tunnel-restoration was used after endodontic treatment. Clinical
      examinations were taken to follow up all the teeth at one year and two years
      respectively after treatment. RESULTS: At one year after treatment, 35 cases were
      followed up, the rate of success was 100%. At two years after treatment, 33 cases
      were followed up and 2 cases were lost, the rate of success was also 100%.
      CONCLUSIONS: Proximal contact point and marginal ridge of the teeth were
      preserved by using tunnel-restoration, which is very important to restore
      proximal contact, enhance the ability of resistance to fracture, and has good
      clinical effect.

PMID- 14661451
TI  - [The effect of pinyangmycin, dexamethasonum and sodium morrhuate injected
      concomitantly to treat cavernous hemangioma].
AB  - OBJECTIVE: The effect of Pinyangmycin, Dexamethasonum and Sodium Morrhuate
      injected concomitantly to treat cavernous hemangioma in oral and maxillofacial
      regions was evaluated. METHODS: The medical records of 350 patients with
      cavernous hemangioma in oral and maxillofacial regions between January 1998 and
      January 2002 were reviewed. One hundred and sixty-five of the patients were men,
      and 185 were women, the sex ratio was 1:1.12. The patients' ages were between 4
      months and 55 years. Two hundred and Twenty-six hemangiomas were located in the
      maxillofacial regions, and 124 located in the oral cavity. The size of the
      lesions varied from 1 cm x 1 cm to 6 cm x 9 cm. Pinyangmycin, Dexamethasonum and
      Sodium Morrhuate were injected simultaneously into the lesions or in the vicinity
      of the cavernous hemangiomas, and the injection might be repeated every 5 to 7
      days when necessary, and this process could be repeated 3 to 5 times. RESULTS:
      Three hundred and fifty patients were followed up for 6-48 months. The cure and
      essentially cured rates were 95.48%, the total efficiency rate was 100%.
      CONCLUSION: This method was a safe, simple and effective therapy to manage
      cavernous hemangioma in the oral and maxillofacial regions.

PMID- 14661452
TI  - [The prevalence of orthodontic treatment need in Urumqi Han's adolescent].
AB  - OBJECTIVE: To assess the severity of malocclusion and the need for orthodontic
      treatment in Urumqi Hans' adolescent. METHODS: 562 children aged from 11-19 years
      old were chosen randomly and were investigated. The severity of malocclusion and
      the need for orthodontic treatment were assessed using the Malocclusion Severity
      Index (MSI, Hill PA 1992). RESULTS: The MSI scores for this population were 21.91
      +/- 17.09 in male and 22.28 +/- 17.26 in female, respectively, there were no
      significant differences between sexes (P > 0.05). According to the
      classifications of MSI scores, the rates of the need for orthodontic treatment
      were 54.55% in male and 55.40% in female. CONCLUSIONS: (1) The rates of
      orthodontic treatment need in Urumqi Hans' adolescent were highly frequent. (2)
      The MSI is a simple precise valid index for assessing the orthodontic Treatment
      Need. It is suggested to be used widely.

PMID- 14661453
TI  - [Relationship of caries experience between primary teeth and the first permanent
      molars in 100 children of 6-year-old].
AB  - OBJECTIVE: To investigate the correlation of caries experience between primary
      teeth and the first permanent molars. METHODS: A total of 100 school children 6
      years old were surveyed. The caries diagnosis criteria defined by WHO were
      employed. The data were statistically analyzed by use of SAS. RESULTS: Fisher's
      exact test showed that there was association between the caries experience of
      primary teeth and that of the first permanent molars in 6-year-old children. The
      average dmft of primary teeth was in positive correlation with DMFT of the first
      permanent molars(r = 0.5629). The results were statistically significant.
      CONCLUSION: The primary tooth caries experience may play an important role in
      predicting permanent tooth caries. More attention was suggested to pay to the
      children with more primary teeth decayed.

PMID- 14661454
TI  - [The clinical observation of different management of relaxion incision in
      palatoplasty].
AB  - OBJECTIVE: To compare the different management of relaxion incision in
      palatoplasty, and the treatment outcome. Methods 40 cases with cleft palate, who
      underwent palatoplasty, were classified into two groups: iodine gauze in incision
      and the control. The body temperature and the sign were recorded. RESULTS: The
      body temperature of the control was lower than that of the group whose incision
      were filled with iodine gauzes. Their complication and duration in hospital was
      less. CONCLUSION: The management of relaxion incision without packed iodine
      gauzes is feasible and safe.

PMID- 14661455
TI  - [Influence of different temperatures on internalization of epidermal growth
      factor receptor complexes in Tca-8113 cells].
AB  - OBJECTIVE: To investigate the effect of different temperatures on internalization
      of epidermal growth factor receptor complexes in human tongue squamous carcinoma
      cells(Tca-8113). METHODS: Human epidermal growth factor r (hEGF) was labeled with
      125I according to Chloramine-T method. The quantity of surface binding and
      internalization of 125I-hEGF in Tca-8113 cells at 4 degrees C and at 37 degrees C
      was compared respectively with radiobinding assay. RESULTS: At 37 degrees C, the
      amount of EGFR complexes internalization exceeded that of surface binding after
      10 min. At 4 degrees C, the level of interlization maintained very low.
      CONCLUSION: The study indicated that the surface binding of 125I-hEGF at 4
      degrees C was steadier than that at 37 degrees C. The study on phenomenon of EGFR
      complexes internalization provide the experimental basis for selecting anti-EGFR
      monoclonal antibody in clinic.

PMID- 14661456
TI  - [Arbitrary primed polymerase chain reaction for the genotypic identification of
      Streptococcus sanguis group].
AB  - OBJECTIVE: To find out an ideal method used in identification of Streptococcus
      sanguis group (SSG) strains by arbitrary primed polymerase chain reaction (AP
      PCR). METHODS: AP-PCR was used to distinguish SSG strains by designing 25 bp
      arbitrary primer 5' AAG AGA GGA GCT AGC TCT TCT TGG A 3'. RESULTS: There were
      great differences in the main band of DNA polymorphism among SSG species. The
      similar band can be obtained from the different DNA extractions in the same
      species. CONCLUSION: AP-PCR may be useful in the identification and
      classification of SSG species.

PMID- 14661457
TI  - [Analysis the effect on the stress of root canal wall of pulpless teeth by
      different degree of root canal preparation].
AB  - OBJECTIVE: To analyze the stress variations of wall of root canal of pulpless
      teeth that resulted from different diameters of root canal. METHODS: On the basis
      of the finite-element model of the mandibular first molar that modified by
      routine, diameter of root canal was modified and enlarged so as to the diameter
      of root canal was 1/3 and 1/2 of root diameter, then modified models were loaded
      and the maximal stress of each part of teeth and wall of root canal was
      calculated. RESULTS: The results revealed that enlargement of root canal diameter
      will bring on increase of stress of root canal wall at the orifice and coronal
      1/3. The stress difference of lateral loading was greater than that of vertical
      loading. CONCLUSION: The principle of root canal preparation should be infected
      material removed and good shape of root canal gained. Over-preparation is
      unnecessary and harmful.

PMID- 14661458
TI  - [The relationship between clasp retention and the depth of undercut].
AB  - OBJECTIVE: To study the relationship between the depth of undercut and the
      retention of clasp, as a basic information in clinic designing of clasp. METHODS:
      The Chatillon force measuring instrument was used to record the retention of 18
      Co-Cr alloy casting Akers clasps when they were dislodging from undercuts of
      different depths (0.25 mm, 0.50 mm, 0.75 mm) on bicuspid and molar. All the data
      was analyzed by ANOVA. RESULTS: It is showed that the deeper the undercuts the
      greater the retention is. The retention of the clasp on molar is greater than
      premolar in the same condition of undercut. The effect of the types of the
      abutment and the depths of the undercut are both obvious on the retention of
      clasp. CONCLUSIONS: Within the elastic limit of the material, the retention of
      clasp and the depth of abutment undercut show a positive correlation.

PMID- 14661459
TI  - [The effect of stress on periodontitis model of guinea pigs].
AB  - OBJECTIVE: To investigate the effect of stress on Guinea Pigs' periodontitis
      model. METHODS: 24 periodontitis models of guinea pigs were provided by
      inoculating Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas
      gingivalis (Pg) in the gingival sulcus. The guinea pigs were divided into two
      groups: stress group(stimulated with cold bath and fright) and control
      group(without stimulations). Three animals of each group were sacrificed
      successively at 1, 2, 4, 6 week after inoculation. Clinical and histological
      evaluation, cortisol concentration examinations, osteoclast and osteoblast
      numbers account were applied. RESULTS: The cortisol concentration of stress group
      was significantly higher than that of control group at 1, 2, 4 week after
      stressed(P < 0.05 or P < 0.01). Pocket depth in stress group was significantly
      deeper than that in control group at 2, 4 week (P < 0.05), Compared with control
      group, the stress group demonstrated more active tissue damage and alveolar bone
      resorption. The bone repair in stress group was not as active as in control
      group. The osteoclast numbers in stress group was significantly higher than that
      in control group at 1, 4, 6 week (P < 0.05). CONCLUSIONS: Stress could enhance
      the destruction of periodontal tissues infected by pathogenic bacteria and
      increase disease susceptibility. It was concluded that stress was a significant
      risk indicator for periodontitis.

PMID- 14661460
TI  - [Research of immunization with recombinant plasmid pcDNA3-pacA and pcDNA3-pacP
      against dental caries in gnotobiotic rats. I: Measurement of specific anti-PAc S
      IgA, IgG, valence].
AB  - OBJECTIVE: In this study, rats were immunized with pcDNA3-pacA and pcDNA3-pacP
      through submandibular gland, the valence of specific anti-PAc S-IgA,IgG were
      measured. METHODS: Gnotobiotic rats were vaccinated with pcDNA3-pacA, pcDNA3-pacP
      and combination use of pcDNA3-pacA and pcDNA3-pacP through submandibular gland.
      The valence of specific anti-PAc S-IgA in salivary, IgG in serum were measured.
      RESULTS: The specific anti-PAc S-IgA, IgG could be detected in all of recombinant
      plasmid groups. The level of salivary specific anti-PAc S-IgA and IgG in pcDNA3
      pacA, pcDNA3-pacP, combination use of pcDNA3-pacA and pcDNA3-pacP groups were
      higher than negative control groups (P < 0.05). CONCLUSION: The recombinant
      plasmid pcDNA3-pacA and pcDNA3-pacP could provoke specific mucosal immune
      responses as a novel immunogen against dental caries.

PMID- 14661461
TI  - [Experimental study on using mGTR and venous autografts to repair facial nerve
      defects in rabbits].
AB  - OBJECTIVE: To observe and compare the effects of using mGTR and venous autografts
      to repair the defect of facial nerve in rabbits. METHODS: mGTR and venous
      autografts were performed on three groups of rabbits. Then physical and
      histological examinations were carried out to get the results of these two repair
      methods. RESULTS: Both the two methods can induce regeneration of facial nerve.
      The mGTR is more effective and faster in repairing the nerve defect. Three months
      after operation, the distance of NCV between bilateral facial nerve in mGTR group
      was (2.10 +/- 1.2) m/s, (6.80 +/- 1.4) m/s in venous autografts, (2.16 +/- 1.6)
      m/s in nerve transplantation group. Histologically, the facial nerve fibers were
      arranged regularly and in continuity in mGTR, the facial nerve fibers were
      arranged irregularly with marked hyperplasia of connective tissues in venous
      autografts three months after repair. CONCLUSIONS: The mGTR is more effective
      than venous autografts in repair of facial nerve.

PMID- 14661462
TI  - [Expression of basic fibroblast growth factor in dental pulp of immature
      permanent teeth].
AB  - OBJECTIVE: To investigate the expression of basic fibroblast growth factor (bFGF)
      in normal human dental pulp of immature permanent teeth. METHODS: The teeth root
      development has been completed 1/3-3/4. Their pulps were immunohisto-chemically
      examined by use of bFGF antibody and image analysis techniques were used for
      evaluation. RESULTS: Staining was strongly positive in immature permanent teeth
      pulp. Image analysis indicated that in the coronal pulp, the gray value of the
      pulp core was higher than that of the outer pulp, while in the root pulp was the
      opposite (P < 0.05). CONCLUSION: bFGF may play a role in dental pulp development
      and maturation.

PMID- 14661463
TI  - [Using mineral trioxide aggregate as a direct pulp-capping material in dogs].
AB  - OBJECTIVE: The purpose of this study was to compare the dental pulp responses in
      dogs after MTA (Mineral Trioxide Aggregate) and a calcium hydroxide (Dycal) were
      applied as pulp-capping materials. METHODS: Twelve cuspids in three healthy adult
      beagle dogs were divided into two groups randomly. MTA or Dycal was used to
      repair the exposed site which was created with a fissure bur in a high-speed
      handpiece with copious water spray at the labial cervical access. Then the cavity
      was filled with glass ionomer cement (GIC). Four months later, the specimens were
      processed for histologic examination to observe the pulpal inflammation and
      dentin bridge formation. RESULTS: Five of six samples capped with MTA were free
      of pulpal inflammation, and all of samples in this group had dentin bridge
      formation. In contrast, all of samples capped with Dycal showed pulpal
      inflammation, and dentin bridge formation occurred in only 2 samples. CONCLUSION:
      MTA is a biocompatible material which can promote dentin bridge formation. It can
      be used as a direct pulp-capping material during vital pulp therapy.

PMID- 14661464
TI  - [Histological evaluation on repair of furcation perforation in dogs using mineral
      trioxide aggregate].
AB  - OBJECTIVE: To investigate histological response to immediate repair of different
      sizes of furcation perforation using MTA, Dycal and GIC. METHODS: Forty-two
      posterior teeth in three adult beagle dogs were randomly divided into two groups,
      small perforation group and large perforation group. Each group was then divided
      into three sub-groups which were repaired with MTA, Dycal and GIC respectively.
      The dogs were sacrificed 4 months later, and the specimens processed and examined
      under the light microscope. Inflammation, epithelial proliferation, and formation
      of hard tissue over the material were evaluated. RESULTS: In teeth repaired with
      MTA, five cases were free of inflammation, and the other nine cases were
      associated with slight or moderate inflammation. There was formation of cementum
      with cementoblast cells around it in four cases. In the group of Dycal, all
      specimens had moderate or severe inflammation. The deposition of irregular
      calcified tissues as well as a large quantity of inflamed cells were found in two
      cases of small perforation. Six cases presented epithelial proliferation. In the
      group of GIC, moderate or severe inflammation was seen in all cases except for
      one case of large perforation with fibrous tissues and sparse inflammatory cells
      around the material. Four cases presented epithelial proliferation. There was
      some relation between epithelial proliferation and size of perforation.
      CONCLUSION: MTA is superior to GIC and Dycal for immediate repairing furcation
      perforation in dogs owing to its less irritation to surrounding tissues and its
      ability to induce the formation of hard tissues.

PMID- 14661465
TI  - [A clinical study on septic arthritis of temporomandibular joint: culture and
      identification of pathogenic bacteria].
AB  - OBJECTIVE: To explore the pathogenic organism of septic arthritis of
      temporomandibular joint and the culture condition of the available bacteria.
      METHODS: Joint fluid was aspirated from 30 patients in recent 5 years. Smear and
      Gram stain of joint fluid were done immediately, then cultured in blood agar,
      bacteria-preserving culture medium, trypticase soy agar(TSA) or trypticase soy
      broth(TSB) under aerobic or anaerobic condition, respectively. Pathogen
      identification was performed with biochemical methods. RESULTS: Microorganism
      were found with Gram staining in 15 out of 30 cases, but the culture of bacteria
      only succeeded in 5 cases. Staphylococcus saprophyticus and Staphylococcus aureus
      were the bacteria isolated. Bacteria was isolated in TSB mostly. CONCLUSIONS: 2
      kinds of microorganism were isolated from joint fluid, and S. saprophyticus was
      reported for the first time. However, the positive rate was low, and the better
      technique for culture was expected.

PMID- 14661466
TI  - [A clinical study on septic arthritis of temporomandibular joint: characteristics
      and diagnosis].
AB  - OBJECTIVE: To investigate the clinical characteristics and the procedure of early
      diagnosis of septic arthritis of temporomandibular joint (TMJ). METHODS: 30
      consecutive patients with TMJ septic arthritis were included in this clinical
      study between 1995 and 2001. Physical examinations, joint fluid analyses,
      radiographic imagings and laboratory studies were performed in all cases.
      Sequelae were evaluated. RESULTS: The clinical data showed 29 of the 30 patients
      were more than 18 years old. The infections of the TMJs were mostly through
      hematogenous route, and the original infectious sites could not be found in many
      cases. The obvious inflammatory symptoms in TMJ areas and severe morbidity were
      not detected in most of the cases (25/30), and a high level of polymorphonuclear
      cells, and some fibro-protein or cartilage fragments were seen in the synovial
      fluid. Microorganism were found with Gram staining in 15 of 30 cases, but the
      culture of bacteria only succeeded in 5 cases. S. saprophyticus and S. aureus
      were the common kinds of bacteria isolated. The sequelae were mild, and most of
      the cases had only postinfectious osteoarthritis. CONCLUSIONS: Nowadays TMJ
      septic arthritis has shown some new characteristics, such as occult original
      infectious sites, atypical and mild symptoms, and slight sequelae; Joint fluid
      analysis is necessary for diagnosis.

PMID- 14661467
TI  - [A clinical study on septic arthritis of temporomandibular joint: treatment].
AB  - OBJECTIVE: To investigate the procedure and effect on treating septic arthritis
      of temporomandibular joint (TMJ). METHODS: 30 patients were treated by antibiotic
      therapy, resting of the jaw, and local therapies. The local therapies included
      arthrocentesis with single needle in 20 joints, arthrocentesis with double
      needles in 13, arthrocentesis accompanied by submandibular drainage of the
      infratemporal space abscess in 1, and arthroscopy in 4. The therapeutic effects
      were judged by joint cavity puncture, mouth opening, jaw pain, and jaw function,
      and so on. Sequelae were evaluated. RESULTS: The overall success rate of the
      treatment was 100% (30/30). The success rates of the 4 different management were:
      14/20 in arthrocentesis with single needle, 9/13 in arthrocentesis with double
      needles, 1/1 in arthrocentesis combined with submandibular drainage, and 4/4 in
      arthroscopy, respectively. The sequelae were mild, and most of the cases had only
      postinfectious osteoarthritis. CONCLUSIONS: Low pressure arthrocentesis,
      antibiotic therapy and resting of the jaw were important components of treatment
      in acute septic arthritis. If infratemporal space abscess was found,
      submandibular drainage should be done. Arthroscopy could be recommended to those
      who haven't got good results by arthrocentesis or those who have already had some
      sequelae, such as TMJ fibrous ankylosis.

PMID- 14661468
TI  - [The use of bone grafts in implant restoration with insufficient bone
      quantities].

PMID- 14661469
TI  - [The effects of distraction rates on mandible and adjacent tissues].

PMID- 14661470
TI  - [The application of rigid internal fixation in zygomatic fractures].

PMID- 14661471
TI  - [An 8-year clinical evaluation of CDIC one stage screw implants].

PMID- 14661472
TI  - [The clinical evaluation of tinidazole-iodoform root canal paste on treatment of
      chronic periapical periodontitis associated with ectopic sinus].

PMID- 14661473
TI  - [Applying self-curing calcium phosphate cement to repair perforated molar pulp].

PMID- 14661474
TI  - [Clinical observation of the use of PerioGlas in the jaw defect and root canal
      therapy].

PMID- 14661475
TI  - [Primary plasma cell sarcoma of the mandible: report of five cases].

PMID- 14661476
TI  - [Electronic publication in medicine].

PMID- 14661477
TI  - [Opinion: turkish in medical communication].
AB  - Several problems associated with the use of Turkish in medical, and in
      particular, radiological communication are addressed in this article. Many words
      used in medical communication in Turkey have been adapted from European
      languages. Incorrect spelling and pronounciation of these words occurs quite
      frequently. A significant proportion of "Turkish" medical vocabulary has been
      inherited from the former invaders of the Turkish, namely the Persian and Arabic
      languages. For a rich and living Turkish in medical communication, we must
      respect our maternal language, prefer the already existing Turkish medical
      terminology, and try to find and introduce Turkish counterparts for new medical
      terms.

PMID- 14661478
TI  - [Status of international radiological publications and archive utilization in
      Turkey].
AB  - PURPOSE: To investigate the use of radiological technology and archive
      utilization in two sampled international radiological journals and radiology
      clinics in Turkey, and to explore the impact of these findings on radiological
      publications. MATERIALS AND METHODS: Randomly selected 22 issues of AJR and
      Radiology, 1037 articles in total, were reviewed. The type of article,
      radiological technique, country of origin, use of advanced technology and
      archiving were defined for each article. Additionally, a questionnaire,
      investigating implementation of various radiological devices, archiving and their
      technical features, was posted to the chairmen of the radiology departments in
      Turkey. RESULTS: Most of the articles (61.4%) originated in US. Studies from
      Turkey constituted 0.9% of the articles. This ratio was 2% for France, which has
      almost the same population as Turkey. Magnetic resonance imaging was used in
      27.4% of cases. Based on our definition criteria, advanced technology and
      archiving were used in 19% and 32%, respectively. Data returns of the
      questionnaire were obtained from 17 of 45 (38%) radiology clinics. Responding
      clinics had conventional radiography, B mode ultrasound and conventional computed
      tomography. Archiving of all radiological examinations, excluding plain
      radiography, was performed in one center while only interesting radiological
      images and variations were stored in 8 departments. Implementation of archiving
      was reported sufficient in three clinics, partly sufficient in ten clinics and
      insufficient in four clinics. Archiving was performed by medical doctors in most
      of the cases (53%). The leading problems of archiving were technical and
      economical insufficiencies (82%). CONCLUSION: Archiving is more commonly required
      than utilization of advanced technology for international radiological
      publications. The rate of articles originating from Turkey was lower compared to
      some countries having the same population as Turkey. The lack of sufficient
      technical infrastructure and shortage of staff may be important reasons for such
      differences.

PMID- 14661479
TI  - [Multi-detector CT angiography: Technique and clinical applications].
AB  - Conventional angiography, which is the gold standard in vascular imaging, is
      invasive and has several known potential complications. Therefore, in recent
      years, less invasive techniques such as computed tomography (CT), angiography and
      magnetic resonance angiography (MRA) have became more widely used. With the
      advent of multi-detector technology, multi-detector CT angiography has replaced
      conventional angiography in most clinical circumstances. In this manuscript, the
      technique and clinical applications of multi-detector CT angiography are
      discussed with various examples.

PMID- 14661480
TI  - [Cranial MR imaging findings of carbon monoxide poisoning in asymptomatic
      patients in the chronic stage].
AB  - PURPOSE: To describe MR imaging findings of the chronic stage of carbon monoxide
      poisoning in asymptomatic patients. MATERIALS AND METHODS: Clinical data of 34
      patients, who had been admitted to our hospital for carbon monoxide poisoning
      were reviewed and invited for control evaluation. Of the patients who accepted,
      ten who had no symptoms and neurological sequelae in the physical examination
      were included in the study. All patients had been in coma on initial admittance
      and had awakened after normobaric 100% oxygen therapy 1-10 years ago. Their ages
      were between 22-57 years (mean, 36.2 years). All patients were examined with
      cranial MR imaging. RESULTS: The most common finding was bilateral symmetric
      hyperintensity of the white matter more evident in the centrum semiovale with
      relative sparing of temporal lobes and anterior parts of frontal lobes on T2
      weighted and FLAIR images in all patients. Subcortical U-fibers were intact in
      all patients. Cerebral cortical atrophy of variable degrees was seen in eight
      patients, mild atrophy of cerebellar hemispheres in seven patients, and vermian
      atrophy in nine patients. Corpus callosum was atrophic in two patients. Bilateral
      globus pallidus lesions were seen in three patients as hypointense on T1-weighted
      and hyperintense on T2-weighted and FLAIR images. CONCLUSION: Cerebral changes
      may be present in patients with severe CO poisoning even when the patient becomes
      asymptomatic. Knowledge of these findings would be helpful when evaluating these
      patients for follow-up or for other reasons.

PMID- 14661481
TI  - [CSF connection of the intracranial cysts and cyst like lesions: Analysis with
      flow sensitive phase-contrast Cine MR imaging].
AB  - PURPOSE: To evaluate the potential role of ECG-gated flow sensitive phase
      contrast cine magnetic resonance (MR) imaging in detecting the communication
      between cystic intracranial lesions and neighboring cerebrospinal fluid (CFS)
      spaces. MATERIALS AND METHODS: Twenty one patients with intracranial cystic
      lesions (arachnoid cyst, 15; epidermoid cyst, 2; glioma, 1; dermoid cyst, 1; and
      mega cisterna magna, 2) underwent CSF flow studies in addition to the
      conventional MR sequences. MR imaging was performed with ECG gated two
      dimensional fast imaging steady-state precession sequence (2D-FISP). Using the
      cine images obtained per cardiac cycle, we tried to identify the communication
      between cysts or cyst-like structures and neighboring CSF spaces. Results were
      compared with intraoperative findings, computed tomography (CT) cisternography
      and scintigraphy. RESULTS: In 14 cystic lesions, no communication was identified.
      In five arachnoid cysts, a pulsatile CSF flow was seen in the cysts. In the two
      enlarged cisterna magnas there was a pulsatile flow coming from the central CSF
      spaces. All intraoperative, CT cisternography and scintigraphy findings were
      compatible with the results of the MR flow studies. CONCLUSION: Cine-mode MR
      imaging with ECG gated 2D phase contrast MR sequence technique is a reliable
      noninvasive alternative to CT cisternography for functional evaluation of the
      cystic lesions, because it enables visualization of the flow communication
      between cysts or cyst-like structures and neighboring CSF spaces.

PMID- 14661482
TI  - [Qualitative and quantitative MRI findings in temporal lobe epilepsy].
AB  - PURPOSE: Mesial temporal sclerosis is the most common pathological finding in
      temporal lobe epilepsy (TLE). Accurate identification and localization of this
      pathology before surgery is obligatory for a good prognosis after the operation.
      In this study we compared the results of qualitative and quantitative MR findings
      of the hippocampus in TLE. MATERIALS AND METHODS: The study group consisted of 42
      patients with the definitive diagnosis of temporal lobe complex partial seizure
      and 42 control subjects. Extrahippocampal lesions had been detected in 10
      patients. Qualitative evaluation was performed by T2-weighted FSE, fast FLAIR, T1
      weighted fast IR sequences on coronal plane. We also performed volumetric
      measurements of the hippocampus in 32 patients with TLE and compared the results
      with those of the control group. The mesial temporal lobes were investigated with
      SVS-proton MR spectroscopy using a PRESS sequence with an echo time of 135
      milliseconds and T2 relaxation values. RESULTS: Hippocampal pathology was
      detected on paracoronal plane at T1-weighted fast IR (84%), T2-weighted FSE (60%)
      and fast FLAIR (88%) images. On comparing the hippocampal volumes of the patient
      and control groups, the hippocampal of the control group were found to be
      significantly larger (p < 0.05). Considering the right-left volume differences,
      28 patients (88%) were found to have unilateral hippocampal atrophy. The most
      consistent MR spectroscopic parameter for definite lateralization was the NAA/Cho
      + Cr ratio (100%). Accurate epileptic focus lateralizations were made in 27
      subjects (84%) by using hippocampal T2 relaxation time, and in 12 subjects (33%)
      by using temporal white matter T2 relaxation time. CONCLUSION: MR imaging is
      highly sensitive in detecting and locating abnormalities in the temporal lobe and
      hippocampus in patients with TLE. Implementation of FLAIR and T1 IR sequences in
      the routine MR examination of patients with TLE is recommended. With adequate
      asymmetry index, NAA/Cho + Cr ratio is sensitive in predicting the side of
      involvement in patients with TLE. For medically intractable TLE patients MRS is a
      very important guiding tool prior to surgery.

PMID- 14661483
TI  - [MR spectroscopy in the differential diagnosis of focal brain lesions in
      neurofibromatosis type 1 patients].
AB  - PURPOSE: To determine the role of MR spectroscopy in the differential diagnosis
      of focal brain lesions in neurofibromatosis type 1. MATERIALS AND METHODS:
      Fifteen patients with neurofibromatosis type 1 were evaluated by routine MRI and
      single voxel MR spectroscopy (TE: 31). The posterior parietal white matter of 20
      age-matched healthy volunteers constituted the control group. NAA/Cr, Cho/Cr and
      MI/Cr ratios were calculated and compared with the control group. RESULTS: A
      total of 58 focal brain lesions were detected by MR imaging. When patients with
      hamartomas and gliomas were compared with the control group, a decrease in the
      NAA/Cr ratio, and a significant increase in Cho/Cr and MI/Cr ratios were found.
      The decrease in the NAA/Cr ratio and the increase in Cho/Cr and MI/Cr ratios of
      gliomas were significant when compared with hamartomas. With MRI and MR
      spectroscopy findings, 52 hamartomas and 6 gliomas were detected. CONCLUSION:
      Since MR spectroscopy has the ability to detect cellular metabolic changes, it
      could provide additional information to MR imaging about the differential
      diagnosis and treatment planning of focal parenchymal lesions in
      neurofibromatosis type 1.

PMID- 14661484
TI  - [Clinical and magnetic resonance imaging findings in patients with surgically
      treated mesial temporal sclerosis].
AB  - PURPOSE: Mesial temporal sclerosis (MTS) is one of the leading causes of
      medically intractable complex partial seizures. Magnetic resonance imaging (MRI)
      and clinical findings in seventeen patients who had surgery for medically
      intractable mesial temporal lobe epilepsy (MTLE) are presented in this report.
      MATERIALS AND METHODS: 17 patients (9 females and 8 males) aged 19-35 years with
      clinically and electrophysiologically proven MTLE have been included in the
      study. Age at seizure onset was six months to 17 years, frequency of seizures 4
      20 times/month, and duration of medical treatment 10-28 years with no response.
      MRI and volumetry of the mesial temporal structures were performed in all
      patients. RESULTS: On preoperative MRI and volumetry, pathologic signal, loss of
      internal structures and atrophy were present in the right hippocampus in twelve
      cases and left hippocampus in five. The hippocampal head and body were involved
      in ten cases and all three parts in seven. The Wada test was performed in three
      cases showing that memory and speech functions were controlled by the noninvolved
      side. All patients underwent surgery. The histopathological examination result
      was MTS in all cases. In the postoperative follow up period of one to 24 months,
      12 patients were assessed as class I and II, and seven as III according to the
      Engel Classification. CONCLUSION: MRI and volumetry are among the most important
      tools in the preoperative diagnosis of MTS. All patients have benefited from
      surgery, verifying the preoperative clinical and MR imaging diagnosis.
      Interpretation of MR findings is important in determining surgical candidates and
      success of surgery in MTS, which is a major cause of medically intractable
      temporal epilepsy.

PMID- 14661485
TI  - [Diffusion-weighted imaging of acute vertebral compression: Differential
      diagnosis of benign versus malignant pathologic fractures].
AB  - PURPOSE: Our purpose was to assess the value of diffusion-weighted steady-state
      free precession (SSFP) sequence for differentiating between benign and pathologic
      compression fractures. MATERIALS AND METHODS: Forty-nine patients with 63 acute
      vertebral compression fractures caused by osteoporosis (n = 23), trauma (n = 7),
      malignancy (n = 30), infection (n = 3) were examined with a diffusion-weighted
      SSFP sequence (diffusion gradient strength; 23 mT/m, diffusion pulse length 5
      ms), T1-weighted turbo spin-echo sequence, and short-inversion-time (TI 150 ms)
      T2-weighted turbo inversion recovery sequence. The signal intensity
      characteristics were analyzed qualitatively and quantitatively for all sequences.
      Statistical analysis was performed with the Student's t test. RESULTS: In
      diffusion-weighted MR imaging, benign osteoporotic and traumatic fractures were
      hypo- to isointense to adjacent normal vertebral bodies. Pathologic and
      infectious compression fractures were hyperintense to normal vertebral bodies.
      Pathologic vertebral fractures had positive bone marrow contrast ratios at
      diffusion-weighted imaging, whereas non infectious benign vertebral fractures had
      negative values (p < 0.001). The difference in bone marrow contrast ratios for
      benign and pathologic compression fractures at T1-weighted TSE and T2-weighted
      turbo IR was not significant (p > 0.01). CONCLUSION: Diffusion-weighted SSFP
      sequence provides unique information that significantly impacts the accuracy of
      radiologic diagnosis. Diffusion-weighted SSFP sequence may allow the
      differentiation of acute benign osteoporotic fractures from malignant compression
      fractures. Acute benign osteoporotic or traumatic fractures show hypointense or
      isointense signal on diffusion-weighted sequences that reflects persistent free
      water proton mobility. Malignant compression fractures show hyperintensity
      compared with normal surrounding bone marrow probably due to altered water proton
      mobility within the neoplasm.

PMID- 14661486
TI  - [Case report: Isolated pituitary sarcoidosis: MRI findings].
AB  - Sarcoidosis is a multisystem granulomatous disease with an unknown etiology.
      Symptomatic central nervous system involvement occurs in 5% of cases. MRI shows a
      wide range of central nervous abnormalities including hypothalamic-pituitary
      infiltrating lesions, cerebral parenchymal masses, leptomeningeal lesions, and
      focal white-matter lesions. The patients with sarcoidosis may rarely present with
      sellar masses. A case of isolated pituitary sarcoidosis was presented in this
      report with pre-treatment and post-treatment MRI pictures.

PMID- 14661487
TI  - [Assessment of mandibular vascular canals by dental CT].
AB  - PURPOSE: Sublingual artery and its branches run in the floor of the mouth and
      prone to substantial bleeding when injured during an implantation procedure.
      These branches enter the mandible from the lingual side and run through bony
      canals in the mandible. The purpose of this investigation is to evaluate the
      frequency, diameter, direction and position of lingual canals by dental CT.
      MATERIALS AND METHODS: 26 patients who underwent dental CT of the mandible before
      implantation were included in this study. Tomographic examination was performed
      in a transverse plane parallel to the mandibular base by bone algorithm.
      Multiplanar reconstructions were obtained in the sagittal and coronal oblique
      planes. RESULTS: All patients demonstrated at least one canal, and 8 patients had
      two or more canals. Two of the patients presented with four canals. The typical
      lingual canal locations were the middle of the mandible and the premolar regions.
      The mean diameter of the lingual canals was 0.8 mm +/- 0.2 mm in the middle, 0.6
      mm +/- 0.1 mm in the premolar regions. The direction of median canal was anterior
      and slightly caudal. Lateral canals were directed in a medial manner. CONCLUSION:
      Before the dental implantation procedure, beside the relationships of implant
      with the important anatomic structures, lingual vascular canals should also be
      evaluated. Dental CT examination easily demonstrates the presence, position,
      direction and size of the lingual canals. By ensuring that radiologists and
      dentists are aware of these canals and their importance, bleeding complications
      during the placement of implants could be avoided.

PMID- 14661488
TI  - [Case report: Cemento-ossifying fibroma of the ethmoidal sinus presenting with
      exophthalmos].
AB  - Cemento-ossifying fibroma is a benign fibro-osseous tumor which contains fibrous
      tissue and varying amounts of calcified tissue resembling bone, cementum or both.
      The tumor is frequently seen in the mandibula and maxilla, but it may rarely
      affect the ethmoidal sinus. In this report, CT findings of cemento-ossifying
      fibroma located in the ethmoidal sinus are presented.

PMID- 14661489
TI  - [Case report: Dermatofibrosarcoma protuberans metastatic to lung without local
      recurrence].
AB  - Dermatofibrosarcoma protuberans is a rare skin tumor which constitutes 6% of soft
      tissue sarcomas. Typically, it has a superficial location and a locally
      aggressive character. Although it has a relatively high recurrence rate, the rate
      of distant metastasis is about 3%. Furthermore, it rarely metastasizes without
      local recurrence. Here we present a case with dermatofibrosarcoma protuberans
      with distant metastasis occurring seven years after the local excision of the
      primary tumor and without any local recurrence.

PMID- 14661490
TI  - [Contrast enhanced power Doppler and color Doppler ultrasound in breast masses:
      Efficiency in diagnosis and contributions to differential diagnosis].
AB  - PURPOSE: To compare ability of detection of vascular structures by utilizing
      ultrasonographic contrast agent (Levovist) prior to and following power Doppler
      ultrasound (PDUS) and colour Doppler ultrasound (CDUS) and to determine useful
      parameters in the differentiation of malignant and benign breast masses by means
      of verified data. MATERIALS AND METHODS: Vascularisation characteristics of 38
      breast masses (22 malignant, 16 benign) which were confirmed by mammography and B
      mode sonography were evaluated by both CDUS and PDUS following and prior to
      intravenous contrast application. In addition, Vmax and RI values of vascular
      structures were calculated by Doppler spectral evaluation. RESULTS: Malignant
      lesions showed more vascularity than benign lesions both with and without
      contrast enhancement. With both methods, by utilizing contrast agent, central,
      penetrating and tortuous vascular structures became more significant in malignant
      lesions when compared with benign lesions. PDUS was able to detect vascular
      structures better than CDUS; however, the difference was not statistically
      significant. Presence of peripheral vascularity was not useful in differentiating
      malignant from benign lesions. Vmax and RI values were higher in malignant
      lesions and the difference was statistically significant. In both methods, Vmax >
      15 cm/sec and RI > 0.80 (CDUS), and RI > 0.70 (PDUS) were accepted as malignancy
      parameters. CONCLUSION: Vascular patterns of breast masses as determined with
      PDUS and CDUS with contrast enhancement and Doppler spectral examinations enabled
      differentiation of malignant and benign breast lesions. Thus, it is possible to
      decrease the number of unnecessary surgical interventions.

PMID- 14661491
TI  - [Effect of different threshold levels and injection rates on hepatic enhancement
      by using bolus tracking technique in helical CT].
AB  - PURPOSE: To evaluate the influence of different injection rates and different
      threshold levels on hepatic enhancement using the bolus tracking technique.
      MATERIALS AND METHODS: One hundred patients were included in this randomized and
      prospective study performed on a helical CT. Patients were assigned to one
      control and four study groups. Each group received 150 ml nonionic contrast
      medium. In the control group, used delay time and injection rate were 60 sec and
      3 ml/sec, respectively. In the study groups, two different injection rates, 3
      ml/sec (groups 1 and 2) and 5 mL/sec, respectively. In study groups, two
      different preselected thresholds, 40 HU (groups 1 and 3) and 50 HU (groups 2 and
      4) were used. In these groups, delay times were determined individually by means
      of the bolus tracking technique. Peak enhancement time (PET), peak enhancement
      value (PEV), and mean hepatic enhancement (MHE) on CT scans was calculated for
      each group. RESULTS: PET was found to be significantly earlier in the study
      groups in which the injection rates were 5 mL/sec, compared to the other groups
      (p < 0.001). MHE was significantly higher in all study groups compared to the
      control group (p < 0.001). PEV was higher in study groups that the preselected
      threshold was 50 HU compared to only the control group (p < 0.01). CONCLUSION:
      Use of a bolus tracking program helps to achieve a greater level of hepatic
      enhancement. Increasing the injection rate shortens the time to peak hepatic
      enhancement. The threshold level of 50 HU achieves a great level of hepatic
      enhancement independent of injection rates in the bolus tracking technique. If
      the bolus tracking technique is not available, using an injection rate of 3
      ml/sec and 70 sec delay time seems to be appropriate.

PMID- 14661492
TI  - [Unenhanced helical computed tomography in the diagnosis of choledocholithiasis].
AB  - PURPOSE: The aim of this study is to investigate the diagnostic value of
      unenhanced helical computed tomography in choledocholithiasis. MATERIALS AND
      METHODS: Unenhanced helical computed tomography was performed in 37 patients with
      findings of obstructive jaundice and suspicion of choledocholithiasis. Results
      were classified as choledocholithiasis and others. In 35 patients the results
      were confirmed by endoscopic retrograde cholangiopancreatography, and in 2 by
      surgery. RESULTS: Choledocholithiasis was detected by unenhanced helical computed
      tomography in 16 patients. In 13 patients, choledocholithiasis was proven by
      endoscopic retrograde cholangiopancreatography and in one patient by surgery.
      Unenhanced helical CT had 93.3% sensitivity and 90.9% specificity in the
      diagnosis of choledocholithiasis. CONCLUSION: Unenhanced helical computed
      tomography may be used as a noninvasive, reliable, and rapid alternative
      diagnostic method in the diagnosis of choledocholithiasis.

PMID- 14661493
TI  - [Case report: Mirizzi syndrome in a patient with emphysematous cholecystitis:
      ultrasonographic and computed tomographic findings].
AB  - Mirizzi syndrome is a very uncommon cause of extrahepatic bile duct obstruction.
      A stone impacts in the cystic duct or gallbladder neck and causes extrinsic
      compression and obstruction of the common hepatic duct, aided by a local
      inflammatory process. Preoperative diagnosis is very important because of the
      potential risk of bile duct injury during surgery and the local inflammatory
      process may suggest cholangiocarcinoma. Infection by specific coliform organisms
      may result in emphysematous cholecystitis in patients with diabetes or those who
      are immunosuppressed, with mural air being visible. Herein, we report an
      emphysematous cholecystitis associated with Mirizzi syndrome in a patient with
      diabetes mellitus.

PMID- 14661494
TI  - [Three dimensional ultrasound volumetric assessment of the synovial fluid in the
      ankle and hindfoot: Technique and normative data].
AB  - PURPOSE: Since synovial fluid is an important marker of disease, we performed
      three-dimensional ultrasound volumetric measurements of synovial fluid to provide
      baseline normative data. MATERIALS AND METHODS: Volume data were acquired using a
      7-10 MHz three dimensional ultrasound probe on 40 ankles in 20 volunteers (25-61
      years). Amounts of fluid were assessed in the ankle joint recesses, bursae and
      tendon sheaths. Images were acquired in the sagittal plane and were reconstructed
      in three orthogonal planes; transverse, sagittal and coronal. Fluid volumes were
      calculated from the volume data set using the manual planimetric method. RESULTS:
      Fluid in tendon sheaths was most common about the peroneals, and unlike prior MRI
      results, was less common around the flexors. In the flexors, fluid was most
      common around the flexor hallucis longus tendon, less common around posterior
      tibial tendon, and rare around fleksor digitorum longus tendon. In the extensors,
      fluid was less common but, when present, of greater volume, especially around the
      extensor hallucis longus tendon. Fluid was most common around the anterior tibial
      tendon and rare around the extensor digitorum longus tendon. Sparse fluid was
      seen in the majority of retrocalcaneal bursae. Fluid in the anterior ankle recess
      was quite common. Visualization of fluid in the posterior ankle recess was
      infrequent. CONCLUSION: Three-dimensional ultrasound permits measurement of fluid
      volume in the normal ankle/hindfoot; normative data are provided.

PMID- 14661495
TI  - [Intraarterial thrombolysis in the treatment of acute ischemic stroke: Technical
      and clinical results].
AB  - PURPOSE: To evaluate the safety and recanalization efficacy of local IA rt-PA
      delivery in patients with acute ischemic stroke. MATERIALS AND METHODS: Fifteen
      patients with acute ischemic stroke were treated; of these, 10 were carotid
      artery stroke, 5 were vertebrobasilar territory stroke cases. The neurological
      status of the patients were graded according to the Glascow Coma Scale and
      National Institutes of Heart Stroke Scale. All patients underwent a CT
      examination on admission. In addition, 4 patients had diffusion-weighted and one
      patient had a perfusion MR examination. Patients of carotid territory stroke were
      treated within 6 hours from the stroke onset. There was no time limitation for
      the basilar artery territory. The Rankin Scale (RS) was used as outcome measures.
      RESULTS: Two of the 10 patients with carotid artery stroke had carotid territory
      occlusions, 8 had middle cerebral artery main trunk occlusions. Four patients had
      symptomatic hemorrhage; of these, 3 died within 24 hours. At the third month 4
      patients had a good outcome. Of 5 patients with basilar artery stroke, 4 had
      basilar artery occlusions. In one patient, the basilar artery was open but the
      flow of the contrast material was very slow. Two patients with unsuccessful
      recanalization due to underlying high grade atherosclerotic stenosis and one
      patient with successful recanalization died. At the third month, the other
      patient with succesful recanalization had a poor outcome (RS 4). The patient with
      slow basilar artery flow developed from RS 5 to RS 1 and was discharged without
      any neurological deficit. CONCLUSION: In acute ischemic stroke, local IA
      thrombolysis is a safe and feasible treatment when the right patient is selected.
      Hemorrhage does not exceed that which occurs in the natural history of the
      disease and with other treatment methods.

PMID- 14661496
TI  - [Uterine leiomyoma embolization: Role of power Doppler ultrasonography].
AB  - PURPOSE: The vascularity of uterine leiomyoma was evaluated by power Doppler
      ultrasonography (PDUS) before and after bilateral uterine artery embolization
      (UAE) in order to establish the efficacy of the procedure and contribution to the
      treatment. MATERIALS AND METHODS: UAE was performed in 20 symptomatic patients
      with uterine leiomyoma. In addition to MRI and gray scale US, patients were
      evaluated by PDUS to assess the vascularity of the uterus and leiomyomas before
      and 6 months after the embolization and the findings were compared with
      angiography. Vascularity was categorized into 3 groups as mild (5 cases),
      moderate (7 cases) and marked (8 cases). Relationship between the findings of
      PDUS and treatment results were analyzed statistically by one-way ANOVA and post
      hoc Tukey tests. RESULTS: In PDUS except their calcified and degenerated regions
      leiomyomas displayed more vascularity peripherally than centrally, before the
      embolization. Six months after the embolization, a decrease of 37%, 44% and 59%
      was observed in the mass of the leiomyomas that had revealed mild, moderate and
      marked vascularity before the embolization. Greater mass reduction occurred in
      leiomyomas with high pre-embolization vascularity (p < 0.05). CONCLUSION: PDUS
      gives important information about the vascularity of uterine leiomyomas before
      and after uterine artery embolization, which became a widespread treatment option
      in recent years. It can be helpful in the selection of patients for uterine
      artery embolization by revealing the vascularity of the leiomyomas. Also it is a
      non-invasive and cheap method in the determination of the efficacy of the
      procedure in the early and late periods after embolization.

PMID- 14661497
TI  - [Endovascular treatment of renal artery stenosis: Technical and clinical
      results].
AB  - PURPOSE: To determine the primary success rate and follow-up results of renal
      artery stenting in controlling renovascular hypertension and renal failure in
      patients with renal artery stenosis. MATERIALS AND METHODS: Balloon expandable
      stents were placed in 40 renal arteries of 35 patients (16 men, 19 women; mean
      age 60, 1). Indications for treatment were hypertension alone in 11 patients,
      disturbed renal functions alone in 12 patients and hypertension associated with
      renal failure in eight patients. Four of the patients were diagnosed during
      angiography due to peripheral arterial diseases. Blood pressures and serum
      creatinine levels were measured before the operation and after stenting. RESULTS:
      The primary technical success rate was 100%. Mean percent stenosis was 81%. The
      lesions were ostial in 28 patients, proximal in 10 patients and distal in 2
      patients. In those patients having at least one year of follow up, the primary
      patency at one year was 93% (14/15). Hypertension was cured in 7 (20%) patients,
      improved in 17 (48.5%) patients and did not respond in 11 (31.5%) patients. Of 21
      patients with disturbed renal function, 12 (57.2%) patients improved, 3 (14.3%)
      patients deteriorated and 6 (28.5%) patients were stabilized. CONCLUSION:
      Revascularization of renal artery stenosis is a simple, efficient and safe
      procedure with high primary technical results, low restenosis rates and
      acceptable complication rates. It has a beneficial effect on blood pressure
      control and a non-deleterious effect on renal function.

PMID- 14661498
TI  - [US-guided glue injection in the treatment of femoral pseudoaneurysms].
AB  - PURPOSE: To evaluate the efficacy of US-guided glue injection in the treatment of
      femoral pseudoaneurysms. MATERIALS AND METHODS: In 13 patients, 14 femoral
      pseudoaneurysms were embolized with direct percutaneous glue injection with
      ultrasonographic guidance. We compressed the aneurysm neck during glue injection
      to prevent distal embolization. RESULTS: All of the patients were treated
      successfully. In each patient, complete occlusion of the pseudoaneurysm was
      achieved without complication. The procedure time varied between 5 and 20
      minutes. CONCLUSION: Direct percutaneous glue injection with ultrasonographic
      guidance is an effective and easy method in the treatment of pseudoaneurysms.

PMID- 14661499
TI  - [Case report: Direct percutaneous placement of tunneled hemodialysis catheter
      into the inferior vena cava in a patient with dialysis access problem].
AB  - The paired hemodialysis catheters were inserted into the inferior vena cava (IVC)
      via translumbar approach in a 48-year-old man for lack of other suitable access.
      The catheter tip was thrombosed 2 months after the procedure. After local
      streptokinase infusion, control venogram showed resolution of the thrombus.
      Translumbar catheterization of the IVC is a safe and effective way in patients
      with thrombosed central venous access.

PMID- 14661500
TI  - [Role of three dimensional spiral CT in the evaluation of craniofacial
      abnormalities in pediatric patients].
AB  - Technological advances in computer image analysis have made possible three
      dimensional surface reformations of anatomic structures from contiguous axial CT
      silices. Three-dimensional spiral CT is a relatively new method and it is very
      useful in the diagnosis and management of craniofacial abnormalities. The purpose
      of this pictorial review is to assess the role of three-dimensional spiral CT in
      the evaluation of craniofacial abnormalities including craniosynostosis,
      hypertelorism, frontonasal dysplasia, hypoplasia of mandible, encephalocele and
      trauma in paediatric patients.

PMID- 14661501
TI  - [Multicystic dysplastic kidney: prenatal and postnatal ultrasonographic
      findings].

PMID- 14661502
TI  - [Infantile hemangioendothelioma].

PMID- 14661503
TI  - [Computed tomographic findings of colon herniating through iliac bone defects].

PMID- 14661504
TI  - [A preliminary study on speech therapy for adult cleft palate patients].
AB  - OBJECTIVE: To study speech feature and treatment of adult with misarticulation by
      review 20 patients' clinical information. METHODS: 20 adult patients (10 male, 10
      female, age ranging from 20 to 38 years, mean age 20.35 years) with
      misarticulation were available for this study. All received specialized
      examination, Chinese speech intelligibility test and blowing test before speech
      treatment, 17 cases underwent posterior pharyngeal flap operation before speech
      treatment. Speech treatment included audio discrimination, behaviour training,
      lip phone training, aspirates and fricatives training, tongue lolling out,
      comprehensive training, et al. RESULTS: All cases were restored normal speech
      approximately after speech treatment, consonants loss and hypernasality of some
      patients totally disappeared. But there were some complications in speech
      treatment of 4 cases. CONCLUSION: The outcome of appropriate adult speech
      treatment was satisfactory, though adult speech treatment was more difficult than
      child's.

PMID- 14661505
TI  - [Change of circulating TNF-alpha in patients with advanced periodontitis before
      and after periodontal initial therapy].
AB  - OBJECTIVE: To investigate the effect of periodontal initial therapy on
      circulating tumor necrosis factor-alpha (TNF-alpha) in patients with
      periodontitis. METHODS: Patients with advanced periodontitis were selected.
      Sulcus bleeding index (SBI), probing depth (PD), and circulating TNF-alpha
      concentration were assessed respectively before and 4-6 weeks after periodontal
      initial therapy. RESULTS: The level of circulating TNF-alpha in patients with
      periodontitis was significantly higher than that in healthy control subjects (P <
      0.01). After periodontal initial therapy, SBI, PD and circulating TNF-alpha
      concentration were reduced significantly (P < 0.01) in patients with
      periodontitis. CONCLUSION: Periodontitis may have profound effects on systemic
      health through the elevation of circulating TNF-alpha. Prevention and treatment
      of periodontitis should be important in maintaining systemic health.

PMID- 14661506
TI  - [A case of malformed root surface groove of maxillary lateral incisor with
      supernumerary root].

PMID- 14661507
TI  - [Clinical diagnosis and treatment of radionecrosis of the jaws: an analysis of 58
      cases].
AB  - OBJECTIVE: To probe into the clinical therapy for radionecrosis of the jaws.
      METHODS: To make a clinical analysis of radionecrosis of jaws in 58 cases.
      RESULTS: Conservative treatment can control the progress of the diseases. The
      cure rate of radionecrosis of jaws was 93.3% by extensive resection of
      sequestrum. The survival rate of transplant flap was 97.1% by immediate
      vascularized tissue graft. CONCLUSION: Radionecrosis of jaws can be cured by
      extensive resection of sequestrum, immediate vascularized tissue grafts can be
      used to repair the surgical defect.

PMID- 14661508
TI  - [Intraosseous neurilemmoma of the jaw: report of 11 consecutive cases].
AB  - OBJECTIVE: This study retrospectively analyzed the clinical data of 11 patients
      with intraosseous neurilemmoma of the jaw, with the purpose of improve its
      diagnosis and treatment. METHODS: 11 patients with intraosseous neurilemmoma of
      the jaw treated from January 1993 to February 2002 were reviewed, including the
      clinical features, pathological findings, immunohistochemical findings, imaging
      examinations and treatment methods. 8 patients with benign lesions were treated
      with radical curettage and cautery. 2 patients with mandibular malignant lesions
      were treated with extended resection and neck dissection. 1 patient with
      maxillary malignant lesion concomitant with neurofibrostosis was treated with
      extensive resection and middle split skin graft and neck dissection, followed by
      chemotherapy and radiotherapy after surgery. RESULTS: The lesions were located in
      the maxilla in 5 patients (1 was malignant). 6 patients had mandibular lesions (2
      were malignant). The X ray findings had some specificity. 10 patients were
      followed up for 7 to 122 months without recurrence. 1 patient with maxillary
      malignant lesion died of multiple metastasis 11 months after treatment.
      CONCLUSIONS: Intraosseous neurilemmoma of the jaw was rarely seen clinically. CT,
      MRI and fine needle aspiration biopsy were beneficial for early diagnosis.
      Surgery is still the dominant choice of treatment. The prognosis of the patients
      was generally good. Adjuvant radiotherapy or chemotherapy had limited value,
      especially for patients with neurofibrostosis. A novel regime called CYVADICDE
      was recently invoked much clinical interest.

PMID- 14661509
TI  - [Research of the puncture depth in treatment of trigeminal neuralgia (TN) by
      radiofrequency thermocoagulation(RFT) under CT location].
AB  - OBJECTIVE: To control the puncture depth properly and avoid the complications, CT
      scan was used to measure the depth as the puncture needle perforated through the
      foramen ovale. METHODS: Analysis of the CT scan diagrams of 121 cases suffering
      from TN cured by RFT, and measuring the puncture depth. RESULTS: The average
      puncture depth was 0.88 cm, the maximum was 1.6 cm, and the minimum was 0.4 cm.
      CONCLUSION: The puncture depth can be manipulated correctly by CT location, the
      second and third branches can be avoided to be damaged within 0.8 cm, and the
      first branch can be avoided to be injured between 1.2 cm and 1.5 cm.

PMID- 14661510
TI  - [Analysis of parotid sialography and intervention in 78 cases of chronic pyogenic
      parotitis].
AB  - OBJECTIVE: To study the value of parotid sialography and intervention in the
      diagnosis and treatment of chronic pyogenic parotitis. METHODS: Undertake the
      technique of parotid sialography with 48% Lipiodol ultra-fluide (France) under X
      ray upon 78 patients who were given systemic anti-infections and supporting
      treatments only with non-obvious-results, and classify all the cases into chronic
      obstructive (21 cases) and nonobstructive parotitis (57 cases) according to the
      results of sialography through microcatheter, then go on with bacterial culture
      and drug sensitivity test. Filling treatments were carried out on obstructive
      parotitis cases through the duct with mixed liquor consisting of 2% lidocanine,
      1% methylviolet. In the same way, alpha-chymotrypsin, amikacin, lidocaine was
      used in nonobstructive cases. RESULTS: The cure rate of chronic obstructive
      parotitis was 80.95%, the cure rate of chronic nonobstructive parotitis was
      87.72%. CONCLUSION: The method of parotid sialography and intervention in the
      diagnosis and treatment of chronic pyogenic parotitis is an effective way to
      treat chronic pyogenic parotitis.

PMID- 14661511
TI  - [Study on perception of Shanghai population with labial profile].
AB  - OBJECTIVE: To investigate the perception of Shanghai population with labial
      profile and evaluate its effect on orthodontic treatment. METHODS: Four facial
      profiles with different labial convexity were drawn with computer aid on the
      basis of the pretty Chinese female cephalometric measurements. 650 panelists were
      selected from Shanghai area including 250 youth with normal profile and 200
      adolescents under orthodontic treatment and their parents. Subjects were asked to
      rank the four facial profiles in descending order of attractiveness. RESULTS: The
      ranking was as follows: slightly straight style, standard style, straight style
      and slightly convex style. The normal male youth preferred more convex style than
      female. Patients with Class profile preferred standard style while Class and
      patients and the parents were fond of slightly straight style. CONCLUSION: People
      in Shanghai area tended to prefer straight profile. The perception with labial
      profile has sex and age difference. It also has difference between non
      orthodontic and orthodontic patients and was influenced by the profiles
      themselves. It was suggested that consultation between orthodontist and patient
      was essential and more attention should be made on the patient's perception with
      labial profile.

PMID- 14661512
TI  - [Study on the reliability of two methods for measurement of root canal
      curvatures].
AB  - OBJECTIVE: To study the reliability of the degree of root canal curvatures with
      Schneider's and Weine's methods. METHODS: Fifty-one selected premolars were
      measured by three trained examiners with Schneider's and Weine's methods.
      RESULTS: Among the three examiners, the datas were not significantly different (P
      > 0.05) and linear correlation existed between the two methods (P = 0.0001).
      CONCLUSION: It was reliable to determine the degree of root canal curvatures
      using the two methods.

PMID- 14661513
TI  - [An analysis of the effect of adult tooth-brushing].
AB  - OBJECTIVE: This study observed plaque distribution on permanent dentition before
      and after brushing to analyze the effect of adult tooth-brushing. METHODS: 81
      undergraduate were included in this study. Recorded the time of tooth-brushing,
      stained with disclosing tablets, plaque deposits on all permanent teeth were
      recorded using plaque index (PLI) before and after tooth-brushing. RESULTS: The
      time of tooth-brushing was from 28 s to 2 min 32 s, the mean time was 57 s, the
      males' was 49 s, the females' was 64 s. Statistically significant differences (P
      < 0.05) were found between males and females. The mean PLI of maxillary tooth was
      0.41 +/- 0.03, for mandibular tooth was 0.47 +/- 0.03, there was significant
      difference between maxillary and mandibular. After brushing, the mean PLI of
      males was 0.532 +/- 0.04, of females was 0.295 +/- 0.03, there was significant
      difference of PLI between males and females (P < 0.05). These tooth PLI score
      were higher than other's mandibular and maxillary molars, these surface PLI score
      were higher than other's, buccal surface of maxillary molars and palatal site of
      maxillary molars. CONCLUSION: People should spend more time on brushing tooth.
      Tooth brushing should be emphasized on these tooth and surfaces with higher PLI
      score. Man should pay more attention to tooth brushing.

PMID- 14661514
TI  - [Clinical studies of calcium hydroxide disinfecting infectious root canal of
      deciduous tooth].
AB  - OBJECTIVE: To search for a more ideal way to disinfect infectious root canal of
      deciduous tooth. METHODS: According to bacterial occurrence and clinical effect,
      40 cases of infectious root canal of deciduous teeth disinfected with Ca(OH)2
      were investigated, the other 40 cases with traditional way of using FC and CP
      respectively, were used as the control. RESULTS: Fist of all, the bacteria of
      deciduous tooth infectious root canal were same as the bacteria of permanent
      tooth infectious root canal. Secondly, Ca(OH)2 was stronger in disinfecting
      deciduous tooth infectious root canal. Thirdly, so far as sterilization was
      concerned, Ca(OH)2 had the same disinfectant as FC, and was better than CP, but
      FC had some irritation and poisonous side-effects to periodical tissue. So
      Ca(OH)2 was safe and effective for deciduous tooth infectious root canal.
      CONCLUSION: It was a more ideal way to disinfect deciduous tooth infectious root
      canal by Ca(OH)2.

PMID- 14661515
TI  - [Sphenozygomatic suture as a guide in the reduction of zygomatic fracture].
AB  - OBJECTIVE: To investigate the effectiveness of sphenzygomatic suture as a guide
      in the reduction of zygomatic complex fracture. METHODS: 36 cases of zygomatic
      complex fracture according to Zingg classification were treated. Reduce
      sphenozygomatic suture first, then reduce the other fracture line and fixed with
      titanium micro-plates. Patients were followed up for 4 weeks to 3 months,
      aesthetic results and X rays symmetry were observed. RESULTS: All patients
      restored satisfactory facial contour, 35 cases got precise reduction, only 1
      patients had slightly discontinued zygomatic arch and infraorbital rim.
      CONCLUSION: During open reduction of zygomatic fracture, reducing sphenozygomatic
      suture first, combined with other fracture lines will reconstruct zygomatic
      complex precisely, and got normal aesthetic outcome.

PMID- 14661516
TI  - [An immunohistochemical study on neovascularization in TMJ during mandibular
      advancement].
AB  - OBJECTIVE: Neovascularization is proved to be closely correlated with
      ossification. This study was designed to determine the biochemical path through
      which the new bone formation is enhanced in TMJ during mandibular protrusion.
      METHODS: SD Rats were fitted with bite-jumping appliances to allow for an
      adequate advancement of the mandible. The animals were sacrificed 3, 7, 14, 21
      and 30 days, respectively, after placement of the appliances. Slides with TMJ
      tissue were prepared for biochemical procedure. Immunohistochemical approaches
      were adopted to examine neovascularization in TMJ by immuno-localizing the newly
      formed endothelial cells. Computer-assisted image analysis system was applied to
      quantify the positive immunoreaction. RESULTS: Neovascularization in connective
      tissue close to the condyle was 200% higher in the experimental groups than that
      in the control, and, within the bony tissue of the condyle, neovascularization in
      experimental animals was found to be 103% higher than that of the control.
      CONCLUSION: Increased neovascularization triggered by mandibular protrusion might
      intensify new bone formation in condyle and glenoid fossa and finally lead to a
      growth adaptation of TMJ to bite-jumping therapy.

PMID- 14661517
TI  - [In situ hybridization analysis of USF1 mRNA expression in odontoblasts].
AB  - OBJECTIVE: To detect and verify USF1 mRNA expression in odontoblasts. METHODS: T
      USF1 clone prepared previously was used as template and the desired USF1 cDNA
      segment was amplified by PCR with specific primers. The segment was labeled with
      digoxin as a probe and in situ hybridization was performed on the mounting of
      odontoblasts. RESULTS: Evidently positive staining was shown in the cytoplasm of
      odontoblasts. CONCLUSION: We verified the expression of USF1 mRNA in odontoblasts
      for the first time and provided evidence for further research.

PMID- 14661518
TI  - [Significance of VEGF expression and microvessel count in oral carcinoma].
AB  - OBJECTIVE: To evaluate the clinical significance of vascular endothelial growth
      factor(VEGF) expression in oral carcinomas. METHODS: Immunohistochemical
      staining(SABC) was used to quantify VEGF expression in specimens from 56 patients
      with oral carcinomas. SPSS statistical software was used for analysis. RESULTS:
      VEGF expression was observed in 29 of the patients(51.8%). The microvessel count
      was significantly higher (P < 0.05) in the oral carcinomas with VEGF expression
      than in the oral carcinomas without it. In the clinicopathologic factors, lymph
      node metastasis(P < 0.05) and differentiated degree (P < 0.05) were significantly
      correlated with VEGF expression, but there was no significantly correlation
      between the clinicopathologic stage and VEGF positive expression. The 5-year
      survival rate after curative surgery was better in the patients without VEGF
      expression (P < 0.05). CONCLUSION: This study indicates that VEGF expression is
      associated with angiogenesis, VEGF is one of the main angiogenic factors for oral
      carcinomas. Quantification of VEGF in oral tissues may provide a valuable marker
      for the prognosis of patients with oral carcinomas.

PMID- 14661519
TI  - [Expression of telomerase and p53 in ameloblastoma].
AB  - OBJECTIVE: To detect the expression of p53 protein, hTR, and hTERT mRNA in
      ameloblastoma (AB) and to investigate the clinical biological characteristics of
      AB. METHODS: We detected hTR and hTERT Mrna in 54 cases of AB by in situ
      hybridization, and p53 protein by S-P method. RESULTS: The positive ratio of hTR,
      hTERT mRNA was 2/7 and 1/7 in normal oral mucosa, 81.2%(13/16) and 87.4% (14/16)
      in odontogenic keratocyst (OKC), 94.4%(51/54) in AB, respectively. There was a
      significant difference in these three groups (P < 0.001). A strong correlation
      between hTR and hTERT mRNA was found (rs = 1.000, P < 0.001). p53 protein was
      expressed in 87.5% (42/49) AB, 44%(11/25) OKC, 33.3%(1/3) normal oral mucosa,
      respectively. A strong correlation between hTERT mRNA and p53 protein was found
      (rs = 0.848, P < 0.001). A moderate correlation between hTR mRNA and p53 protein
      was found (rs = 0.536, P < 0.001). CONCLUSION: The positive ratios of hTR and
      hTERT were higher than p53 protein in AB. Telomerase activity and p53 expression
      play an important role in genesis and development of AB.

PMID- 14661520
TI  - [The effect on anti-acid corrosion resistance of Ni-Cr alloy coating titanium].
AB  - OBJECTIVE: The aim of this study was to investigate the variation of the
      corrosion resistance of Ni-Cr alloy in acid environment before and after coating
      titanium in vitro. METHODS: 1. Surface treatment using sol-gel technique of
      coating titanium. The steps were as follows: (1) Pre-treatment: sanding, washing
      and activation in order to remove the oxidative product; (2) The preparation of
      sol: some small charged particles produced by the hydrolytic reaction, and formed
      sol. These particles would congeal into extremely small ones (diameter usually is
      5 microns); (3) Coating; (4) Heat treatment: The organism was resolved and
      volatilizeed at high temperature, and the atoms of Ti were left. These atoms of
      Ti were very active and could combine firmly with the atoms on the surface
      awaiting of treatment. 2. CONDITIONS: artificial saliva; pH = 7.0 and pH = 5.6;
      temperature: 36.5 degrees C 3. Electrochemical test: polarization curve;
      instrument: ZF-3 poteniostat. RESULTS: Before coating titanium, when pH was 7.0,
      the electrode potential of Ni-Cr alloy was -160 mV, and the self-corrosion
      current density was 0.262 microA cm-2; when pH = 5.6, the data were -182 mV and
      0.352 microA cm-2, respectively. This result showed that when pH value reduced,
      the potential and current density descended, too. This indicated that the
      material was easy to be corroded. After coating titanium, when pH value was 7.0,
      the potential was -71 mV, the self-corrosion current density was 0.152 microA cm
      2; when pH = 5.6, the data were -89 mV and 0.174 microA cm-2. This indicated that
      the corrosion rate of material descended evidently after coating titanium in acid
      environment. CONCLUSION: (1) Not only before coating Ti but also after coating,
      the corrosion resistance of Ni-Cr alloy would descend in acid environment;(2) In
      acid environment, the corrosion resistance of Ni-Cr alloy after coating titanium
      was superior to that of the material before coating. So was in neutral
      environment.

PMID- 14661521
TI  - [Relationship of apoptosis and expression of Fas gene in tongue squamous cell
      carcinoma cell line Tca8113].
AB  - OBJECTIVE: To investigate the relationship of apoptosis and expression of Fas
      gene in oral squamous cell carcinoma. METHODS: Plasmid including Fas gene was
      transfected into Tca8113 cell by lipofectamine kit. The expression of Fas mRNA in
      transfected and non-transfected cell was detected by RT-PCR. The expression of
      Fas protein and apoptosis index(AI) was assessed by flow cytometry(FCM). RESULTS:
      No variation of positive expression rate of Fas protein was found in Fas
      transfected and non-transfected Tca8113 (P > 0.05), but the expression of Fas
      mRNA, intensity of Fas protein and apoptosis index were significantly increased
      respectively from 0.201 +/- 0.015, 31.02 +/- 4.63, 0.88% +/- 0.16% to 0.399 +/-
      0.073, 54.32 +/- 6.38 and 10.21% +/- 1.46%(P < 0.01). CONCLUSION: Apoptosis in
      tongue squamous cell carcinoma was not directly associated with the positive
      expression rate but intensity of Fas protein. A liminal value might exist before
      apoptosis in Tca8113 cell could be activated.

PMID- 14661522
TI  - [The development of maxilla in unoperated cleft lip and palate patients].

PMID- 14661523
TI  - [DNA microarray for gene expression analysis of human oral cancer].

PMID- 14661524
TI  - [Identification and management of difficult airway during perioperative period].

PMID- 14661525
TI  - [Clinical classification and treatment options of mandibular condylar process
      fractures].

PMID- 14661526
TI  - [Evaluation of shear bond strengths of vertically fractured molars by three
      adhesive systems].

PMID- 14661527
TI  - [Surgical correction of inversed impacted maxillary permanent incisor of
      children: report of four cases].

PMID- 14661528
TI  - [Preliminary experience in using VITA3D-MASTER color matching system for color
      selection of PFM crowns in the anterior teeth].

PMID- 14661529
TI  - [Age-related post-translational modification of proteins in human tissue and its
      use determination of age in forensic medicine. Review].
AB  - This article deals with some of posttranslational modification of proteins which
      are, or could be useful to work out objective and standard methods for age
      estimation in forensic medicine. From many posttranslational modifications other
      than racemization, the evaluation of pentosidine, one of the products of
      nonenzymatic glycosylation, seems to be promising. The enlargement of menu of
      methods for age estimation is important mainly for forensic sciences when
      determination of the age of an unknown dead body is necessary. Morphological
      methods are quite often subjective and charged with errors.

PMID- 14661530
TI  - [Energy-dispersive x-ray fluorescence spectrometry--a forensic chemistry method
      for determination of shooting distance].
AB  - The article follows up the experiences Energo-dispersive X-ray fluorescence
      spectrometry (EDXRF) as the forensic necrochemical method as the tool for
      detection of metals (gunshot residues--GSR) in connection with gunshot-wounds of
      persons--authors: dipl. Ing. J. Havel and dipl. Ing. K. Zelenka and Energo
      dispersive X-ray fluorescence spectrometry (EDXRF) as the forensic method as the
      tool for identification of inlets (gunshot--entries) and outlets (gunshot--exits)
      -author: dipl. Ing. J. Havel.

PMID- 14661532
TI  - [Selective pharyngeal brain cooling].
AB  - Whole-body cooling can be used in the treatment of various brain pathologies, for
      example, after hypoxic events. Potential complications include haemodynamic
      instability, coagulation disorders and infection. Selective brain cooling (SBC)
      would therefore appear to make good sense. In an animal model a new approach to
      SBC was therefore evaluated. A rat weighing 350 g was sedated with alpha
      chloralose (40 mg/kg/h) and d-tubocurarine (4.05 mg/kg/h), mechanically
      ventilated and placed on a heating pad. A thermocouple was introduced into the
      somatosensory cortex to a depth of 2.5 mm. SBC was achieved using a novel
      approach: PTFE tubing (ID 100 microns) with an inlet and an outlet was wrapped
      around and glued to a piece of wood, and introduced non traumatically into the
      pharynx. The tubing was perfused with cold water (+4 degrees C). Under SBC the
      cortical temperature dropped from 38.4 degrees C to 27.7 degrees C while the core
      temperature remained stable. In an animal model SBC was successfully accomplished
      via the pharynx. Further studies should now be done to evaluate the effectiveness
      of this approach in larger animals with potentially different anatomical
      features.

PMID- 14661533
TI  - Comparative study of the thermal properties of mud and peat solutions applied in
      clinical practice.
AB  - Different peloids as e.g. mud and peat have been traditionally used for
      therapeutic purposes successfully, especially of there thermal actions. It was
      the aim of the experimental study to compare the thermal properties of two
      peloids, mud and peat, with a view to assessing their thermal effects when they
      are applied in clinical practice. The studies were carried out using peat of the
      marsh type of peats (Hochmoor), and curative Pomorie (Bulgaria) mud. As important
      parameters were determined the specific thermal capacity at constant pressure
      (Cp), the density of solutions (rho), the cooling rate (m), the coefficient of
      temperature transfer (a) of solutions and the coefficient of thermal conductivity
      (lambda) of solutions of peat and curative mud, compared to water bath. The
      comparative studies of the thermal properties of water and water solutions of
      peat and curative mud show that the thermal effect of the water bath is
      substantially smaller than that of the peat and mud applications. This difference
      is due to a greater extent to the high values of the dynamic viscosity, not
      allowing cooling by convection and protecting the surface of the skin upon
      applications of peloid solutions with a higher temperature.

PMID- 14661534
TI  - [Cognitive processes and dynamic time structures. Introduction of a measuring
      instrument for studying the Micro-Vigilance-Shift-(MVS) hypothesis].
AB  - The psychophysiological measuring method for the determination of the auditory
      order threshold (OT) is steadily gaining in importance, both for the diagnosis
      and treatment of speech disorders. Observed intraindividual variability of (macro
      ) vigilance led to the hypothesis of discontinuous cognitive processing in the
      central nervous system. The base for the variability of microvigilance is
      hypothesized to be in the phase difference of the alpha rhythm. To test for this
      hypothesis, we developed an EEG-comparator, which allows for a phase-dependent
      triggering of external stimuli. In direct comparison with stochastic (i.e. non
      phase-dependent) stimulus presentation, the threshold in phase-dependent OT
      testing is distinctly lower. Optimal results occurred at phase angels of phi = 90
      degrees and phi = 270 degrees. Our findings support the hypothesis of a
      correlation between alpha rhythm and vigilance processes. Furthermore, there
      seems to be evidence that memory processes go with changes in vigilance, and in
      this context the alpha phase correlation seems to be important.

PMID- 14661535
TI  - [Three-dimensional-segmentation of the spine with specially adapted tools].
AB  - Segmented 3-D data of the spine form the basis for various modern clinical
      applications. Among these, multisegmental image fusion, image registration and
      finite element modeling for biomechanical analysis are promising innovative tools
      capable of facilitating treatment decisions and optimization of individual
      therapy in the future. However, the complex anatomy of the spine and the often
      extensive degenerative deformation presenting in clinical practice, generally
      limit the application of fully automated segmentation. A newly developed software
      system is presented that meets the complex requirements for image segmentation of
      the spine through the use of specially adapted interactive tools that take
      account of its axial skeletal structure. Furthermore, a standardized protocol is
      introduced that combines the newly developed interactive tools (rotation
      transformation, warped dissection plane) and standard segmentation tools to
      permit rapid and accurate segmentation. To date, the software environment
      presented herein has been applied with success to the segmentation of cervical,
      thoracic and lumbar spine.

PMID- 14661536
TI  - [Biomechanical investigations of different osteosynthesis procedures in the
      proximal tibia-introduction of a new measuring system].
AB  - In this article a new measuring system for biomechanical studies of various
      osteosynthesis procedures on the tibia is described. The paired tibias are
      osteotomized and embedded in PMMA in accordance with a randomization protocol.
      Testing is then carried out under nonaxial loading at 350 N, 600 N and 900 N,
      uniaxial bending applying a force of 12 Nm, and torsion at a force of 5 Nm in a
      universal pneumatic testing machine. Ultrasonic sensors pick up movement at the
      fracture gap under external loading. Testing of the measuring setup has been
      successful, and relevant results were obtained.

PMID- 14661537
TI  - [Systematic analysis of ground reaction forces before and after hip and knee
      arthroplasty].
AB  - In this prospective study we employed a newly developed gait analysis system to
      compare the ground reaction force patterns in 15 patients before and after total
      hip or knee replacement. In this system, data are measured separately for each
      limb. Measured data were also obtained from 30 healthy adults and compared with
      those obtained from the patient group. We analysed the three-dimensional force
      patterns, impulse, frequency, stride and double stance, and compared changes in
      the postoperative gait patterns. The vertical force maxima Fy identify the peak
      forces obtaining during walking. The results showed significantly increased (p <
      0.05) postoperative force maxima Fy2 and Fy3 for both knee replacement (Fy2:
      82.48 to 86.17 and Fy3: 96.09 to 99.35% body weight, pre- and postoperatively,
      respectively) and hip replacement (Fy2: 84.44 to 88.08 and Fy3: 98.63 to 101.96%
      body weight, pre- and postoperatively, respectively). The ADAL system proved
      suitable for the easy performance of gait analysis, and thus may be of future
      value in the area of clinical quality assurance.

PMID- 14661538
TI  - [A novel molecular mechanism involving neuropilin-1 for vascular endothelial
      growth factor-induced retinal angiogenesis].
AB  - PURPOSE: The Neuropilin (NRP) family is a novel receptor family that has been
      found to bind to a key molecule in angiogenesis, vascular endothelial growth
      factor (VEGF). In vascular endothelial cells, NRP-1 functions as an isoform
      specific receptor for VEGF165 and has predominant expression compared to NRP-2.
      Since little is known about its role in pathologic angiogenesis, we studied it in
      retinal angiogenesis. RESULTS: In cultured bovine retinal endothelial cells
      (BREC), VEGF selectively up-regulates NRP-1 expression. This response is mediated
      by VEGF receptor-2 (VEGFR-2) and transcriptional activation. NRP-1 functional
      blocking antibody inhibited VEGF-induced mitogenesis of BRECs in vitro. Moreover,
      inhibition of NRP-1 in a murine model of angioproliferative retinopathy reduced
      angiogenic response in the retina. CONCLUSION: Our results suggest that NRP-1
      plays a critical role in VEGF-induced retinal angiogenesis and thus could be a
      viable therapeutic target for inhibition of retinal neovascularization.

PMID- 14661539
TI  - [Molecular mechanism for choroidal neovascularization in age-related macular
      degeneration].
AB  - Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) is
      the most common cause of severe visual loss in patients over age 60 years in
      developed countries. While much is unknown about the underlying pathogenesis of
      CNV, the increased production of vascular endothelial growth factor(VEGF) by
      retinal pigment epithelium (RPE) is thought to play a central role in the
      development of this condition. However, recent studies using gene-manipulated
      mice question the importance of VEGF alone in promoting CNV. Angiogenesis is
      thought to result from the balance between angiogenesis stimulation and
      inhibition. A potent antiangiogenic factor recently has been identified in the
      retina and shown to be secreted by RPE cells. The inhibitor, pigment epithelium
      derived factor(PEDF) is considered the key factor associated with avascularity of
      the cornea, vitreous, and outer retinal layer of the eye. We recently
      demonstrated that an imbalance between PEDF and VEGF in RPE cells caused by aging
      and oxidative stress may contribute to the disregulation of endothelial cell
      proliferation in CNV. In this review, we also discuss the angiogenic role of
      inflammatory cells in CNV, age-related changes in Bruch's membrane, and the
      possibility of the development of animal models reflecting CNV in AMD.

PMID- 14661540
TI  - [Pulsatile ocular blood flow and choroidal blood flow in age-related macular
      degeneration].
AB  - BACKGROUND: The determination of pulsatile ocular blood flow (POBF) by measuring
      intraocular pressure pulse is a reliable way of evaluating choroidal blood flow.
      METHODS: We studied ocular haemodynamic abnormalities by examining the choroidal
      blood flow using POBF in patients with age-related macular degeneration (AMD).
      RESULTS: POBF was lower in patients with exudative AMD than in patients with non
      exudative AMD and normal subjects. CONCLUSION: The decreased choroidal blood flow
      may induce choroidal neovascularization via angiogenic factor induced by hypoxia
      in patients with exudative AMD. Further studies of choroidal circulation, which
      may be important for the understanding the mechanism of AMD, are needed.

PMID- 14661541
TI  - [Proliferative regulation in the cornea and lens].
AB  - PURPOSE: To examine the mechanism of regulation of proliferation in epithelial
      scraped cornea and the developing lens. METHOD AND RESULTS: C57B16 mouse, p27
      (KIP 1)-/- mice, Skp2-/- mice and Skp2-/-/p27 (KIP 1)-/- double knockout mice
      were examined by immunocytochemistry using anti-p27 (KIP1) antibody, and cells in
      the "S" phase of DNA synthesis were analyzed by immunocytochemistry using anti
      BrdU antibody. The p 27 (KIP 1) was expressed in basal cells of the central and
      peripheral region of the cornea and limbus. This expression was not detected 24
      hr after epithelial scraping, when there were many cells in the "S" phase of DNA
      synthesis in the corneal epithelium. There was no obvious difference in the
      thickness and anti-BrdU staining in the corneal epithelium of p 27(KIP 1)-/- mice
      from that of controls. 24 hr after the epithelial scraping in the Skp 2-/- mice,
      the corneal epithelium was thinner than in wild-type mice and had many p 27(KIP
      1) positive cells and few BrdU positive cells. In contrast, 24 hr after the
      epithelial scraping in the Skp 2-/-/p 27(KIP 1)-/- double knockout mice, the
      corneal epithelium was as thick as in wild-type mice and had many BrdU positive
      cells. CONCLUSIONS: These results suggest that degradation of p27(KIP1) by Skp 2
      is involved in the regulation of proliferation in response to wounding of the
      corneal epithelium. To examine the involvement of the c-maf gene in the
      proliferation of the lens cells, eyes of the E13 and E18 stages of wild-type and
      c-maf-/- mice were analyzed by BrdU incorporation assay, TUNEL assay, and
      immunocytochemistry using an anti-P 27 (KIP 1) and an anti-P 57 (KIP 2) antibody.
      In the E 13 and E 18 c-maf mutant lens, BrdU-positive cells were detected at the
      posterior region of the lens. Cell-cycle inhibitor P 27 (KIP 1) and P 57 (KIP 2)
      were expressed in the equatorial and posterior region of the lens of both wild
      type and c-maf-/- lenses. These results suggest that the expression of c-maf is
      required for differentiation and cell cycle arrest of lens cells independent of p
      27 (KIP 1) and p 57 (KIP 2).

PMID- 14661542
TI  - [Molecular genetic analysis for Japanese patients with autosomal dominant
      retinitis pigmentosa].
AB  - PURPOSE: To identify the common mutations in Japanese patients with autosomal
      dominant retinitis pigmentosa(ADRP), and to show that the kind and frequency of
      mutations depend on race. METHODS: Previously reported mutations for ADRP are
      summarized, and the results of screening for 120 Japanese patients with ADRP of
      the human retinal bascin (FSCN 2) gene are presented. Clinical features are
      characterized by visual acuity, slit lamp biomicroscopy, fluorescein angiography,
      electroretinography, and kinetic visual field-testing. RESULTS AND CONCLUSION:
      The Pro 23 His and Pro 347 Leu mutations in the rhodopsin gene are representative
      mutations for ADRP in other countries, but the mutation in the rhodopsin gene is
      very rare in Japanese patients with ADRP. On the other hand, a novel 208 delG
      mutation in the FSCN 2 gene was identified in 14 patients from 4 Japanese
      families with ADRP. This mutation was found in 3.3% of patients with ADRP, which
      suggests that this mutation might be relatively common and characteristic in
      Japanese patients with ADRP.

PMID- 14661543
TI  - [Surgical removal of juxtafoveal and extrafoveal choroidal neovascularization in
      age-related macular degeneration].
AB  - PURPOSE: In the treatment of age-related macular degeneration (AMD), the effect
      on the fovea of photocoagulation of juxtafoveal choroidal neovascularization(CNV)
      and extrafoveal CNV near the fovea has been of concern, and so usefulness of
      surgical excision of CNV was evaluated. SUBJECTS AND METHODS: Fifteen eyes with
      AMD that underwent removal of juxtafoveal CNV and extrafoveal CNV near the fovea
      and had been followed for over one year were included in this study. Eligibility
      criteria were preoperative visual acuity of 0.3 or less and evidence of CNV
      activity by fundus angiography. RESULTS: Visual acuity of 0.4 or more was
      obtained in 60% of the eyes with best visual acuity and 47% with final visual
      acuity. The mean best visual acuity was 0.51 in cases with Gass type 2, 0.51 in
      type 1 + 2 CNV, and 0.21 in type 1 CNV. Good post-operative visual acuity was
      obtained in type 2 and 1 + 2 cases with type 2 CNV at the foveal side accompanied
      by preoperative foveal retinal sensitivity of 25 dB or more. There was little
      improvement of visual acuity in type 1 CNV because the retinal pigmented
      epithelium defect occurred at the fovea. CONCLUSION: For juxtafoveal CNV and
      extrafoveal CNV near the fovea in AMD, type 2 and 1 + 2 cases with type 2 CNV at
      the foveal side are thought to be candidates for surgery. Especially, relatively
      good postoperative visual acuity was obtained in cases with preoperative foveal
      retinal sensitivity of 25 dB or above. Active surgical removal is thought to be
      indicated for these cases.

PMID- 14661544
TI  - [Near triad meter--dynamic measurement of pupillometry with horizontal eye
      tracker by accommodative stimulation].
AB  - PURPOSE: A newly developed "Near Triad Meter" is a useful tool to record the
      dynamics of pupils and horizontal eye movements in both eyes simultaneously with
      the accommodative stimuli. The responses show insufficiency or strain for
      accommodation. In this study the objective accommodative power (in diopters, D)
      is calculated by the measurement of pupillary constriction-ratio(CR) and compared
      in 4 age groups to find the age-related decrement of diopter values. METHOD: A
      clearly visible accommodative target was moved back-and-forth from 50 cm to [near
      point + 1 D] (maximum accommodative stimulus; MAS). The speed was regulated
      constant for diopter movement. Pupillometry and eye tracker were recorded
      simultaneously with MAS in both eyes together. Three trials were done on 42
      volunteers in each age group from 20-year-olds to 50-year-olds and the most
      reliable recording was used to measure the CR. Eighteen well-responding
      volunteers were selected to make the standard curves of CR by step-by-step
      accommodative stimuli. The mean CRs of initial tests with MAS were applied to the
      age-matched standard curves to calculate the maximum accommodative diopter value.
      RESULTS: The mean CRs versus MAS in each age group were 48%/7.2 D in the 20-year
      group, 46%/6.9 D in the 30-year group, 35%/3.6 D in the 40-year group, and
      33%/3.1 D in the 50-year group. The mean values of CR were applied to age-matched
      standard curves to obtain the maximum accommodative power, which was 8.0 D in the
      20-year group, 9.1 D in the 30-year group, 3.4 D in the 40-year group, and 4.1 D
      in the 50-year group. The 20- and 30-year olds showed equal power statistically,
      The remarkable age-dependent difference was calculated quantitatively.
      CONCLUSION: The dynamics of near response revealed the individual summation of
      accommodative power including depth of focus, and accommodative vergence
      objectively and quantitatively. This method is useful for understanding the
      quality of accommodative insufficiency and also the quantity of accommodative
      width, including presbyopia.

PMID- 14661545
TI  - [Preparation of high-purity and safe autologous plasmin and its clinical
      application].
AB  - PURPOSE: To report an improved preparation of safer and highly-purified
      autologous plasmin and to demonstrate its clinical applications. METHODS: Prior
      to clinical application, animal experiments were carried out. In addition, the
      activity of plasmin in the vitreous cavity after injection was measured serially.
      In preparation for clinical use, the proteinase inhibitors aprotinin and
      benzamidine were used for suppression of protein denaturation. The samples were
      incubated for 48 hours to check for contamination. The preparation was applied to
      patients with idiopathic macular hole and diabetic macular edema. RESULTS: The
      plasmin detached the vitreous body from the inner limiting membrane of the retina
      without any ill effects in animal experiments. The specific activity reached a
      peak in 5-10 minutes and decreased rapidly thereafter. By adding a suppressor of
      protein denaturation in the purification process, 0.2 IU (0.1 ml) of high-purity
      plasmin could be prepared from each patient. No bacterial contamination was
      noted. Complete vitreous detachment could be induced in two clinical cases.
      Urokinase was used instead of streptokinase to activate plasminogen. CONCLUSIONS:
      Vitreous detachment is considered to be induced safely and consistently by
      injection of plasmin prepared using a protein denaturation suppressor and
      activated with urokinase. This method is expected to be of clinical value.

PMID- 14661546
TI  - [Comparison of corneal and conjunctival rose bengal staining before and after
      punctal occlusion].
AB  - PURPOSE: In severely tear-deficient dry eye patients whose puncta had been
      occluded, corneal and conjunctival rose bengal (RB) staining were graded and
      compared to before occlusion. SUBJECTS AND METHODS: Subjects were 17 eyes of 13
      severely tear-deficient dry eye patients whose puncta had been successfully
      occluded (corneal fluorescein staining showed A 0 D 0 after occlusion). Corneal
      and conjunctival RB staining were graded 0, 1, 2 or 3, according to severity [B
      1] at the cornea and at the temporal and nasal bulbar conjunctiva. The scores
      were then compared to those before punctal occlusion. To enable comparison of pre
      and post-occlusion ocular surface concentrations of RB [B 2], post-occlusion
      concentration was adjusted by absorbing tears from the conjunctival sac with
      Schirmer's test paper until the lower meniscus height was equal to that before
      occlusion, as monitored by video-meniscometer. RB dye was then instilled into the
      patients conjunctival sac. RESULTS: RB staining score at the cornea decreased
      significantly; in contrast, no significant improvement was found at the nasal and
      temporal conjunctiva (p = 0.0025, p = 0.05, p = 0.7, respectively, Wilcoxon
      test). CONCLUSION: In accordance with the basic interpretation of RB staining,
      these results imply that RB positive staining [B 3] on the conjunctival surface
      is caused by a factor other than aqueous deficiency.

PMID- 14661547
TI  - [A case of primary congenital glaucoma with unilateral corneal amyloidosis].
AB  - BACKGROUND: Histopathological evaluation of primary congenital glaucoma with
      extensive corneal amyloidosis. CLINICAL FINDINGS: A three-month-old infant. At
      the first examination, corneal diameter was 12 mm in both eyes, intraocular
      pressure (IOP) 43 mmHg in the right eye and 47 mmHg in the left eye. A diagnosis
      was made of primary congenital glaucoma. At 4 months of age bilateral goniotomy,
      at 1 year and 2 months of age bilateral goniotomy, and at 2 years and 2 months of
      age bilateral trabeculectomy and the superficial keratectomy of the right eye
      were done. At 14 years and 11 months of age the enucleation of the right eye was
      done because of corneal opacity, visual loss, and figure. HISTOPATHOLOGICAL
      FINDINGS: In the cornea disappearance of Bowman's membrane, accumulation of
      amyloid in the rough endoplasmic reticulum of the basal cells and subepithelial
      fibroblasts, and thickeniny of Descemet's membrane could be seen. At the
      peripheral anterior synechia new Descemet's membrane was spread over the anterior
      surface of the peripheral iris. CONCLUSION: Unilateral corneal amyloidosis might
      have been present in infancy, amyloid produced in the rough endoplasmic reticulum
      of the basal epithelium and subepithelial fibroblasts and deposited in the
      subepithelial region. At puberty amyloid might have been produced in the
      subepithelial fibroblasts. The poor IOP control at puberty might have been due to
      the complication of neovascular glaucoma.

PMID- 14661548
TI  - [Low-dose multi-slice CT (LMCT) assessment of pulmonary emphysema in public
      school teachers].
AB  - Although rates of emphysematous change in smokers have been reported previously,
      the precise effects of smoking on emphysematous change have not been established
      because the study subjects of previous reports were heterogeneous. This study was
      designed to determine the incidence of emphysematous change identified by LMCT
      imaging in public-school teachers. We reviewed 1776 consecutive subjects (ages
      from 31 to 61 years) who had undergone LMCT scanning during health care
      examinations. In addition, their replies to questionnaires about smoking were
      obtained. Emphysematous change was found by LMCT imaging in 22 male smokers. In
      these 22 smokers, the scores of emphysematous change according to Goddard's
      method was well correlated with smoking history. According to the questionnaires,
      the smoking rates of male and female teachers were 56.7% and 4%, respectively.
      Eighty-five percent of the teachers worked in offices separated from smokers.
      Most smokers wished to quit smoking and most teachers knew the risk of nicotine
      as well as the rate of smoking among high school students. However, knowledge of
      the relationships between smoking and lung cancer, myocardial infarction, and
      subarachnoid hemorrhage were not adequate. Our present study clearly demonstrated
      the incidence of emphysematous change in school teachers. In addition, early
      exposure to information about the risks of smoking is believed to be important
      for students, but school teachers did not have enough of such information.

PMID- 14661549
TI  - [Clinical evaluation of bronchial asthma complicated with sarcoidosis].
AB  - The clinical features of 25 asthma cases complicated with sarcoidosis were
      evaluated retrospectively. In our department, 8 patients (6%) out of 134 with
      sarcoidosis had asthma. The complication was found more frequently in females
      than in males, and the age of onset of the asthma extended from 2 to 63 years.
      Neither the severity nor the type of asthma showed any distinct pattern. In terms
      of chest radiographs of sarcoidosis, stage II was more common in our cases, while
      stage I was more common in the reported cases. In our cases, the severity of the
      asthma remained stable irrespective of the activity of the sarcoidosis. In the
      reported cases, the two diseases showed similar courses. The deterioration of
      each disease was associated in few cases with improvement in the other. In
      summary, the present study suggests that inflammation of the airways in asthma
      and sarcoidosis probably affect their course so that the two diseases improve or
      deteriorate together.

PMID- 14661550
TI  - [Results of survey of adult community-acquired pneumonia utilizing flow chart of
      diagnostic guideline for management of respiratory infections].
AB  - We performed a nationwide survey of 1,258 patients to assess the treatment of
      community-acquired pneumonia in Japan. Cases were classified as bacterial
      pneumonia in which the causal organism was unknown (Type A) or presumed (Type B),
      atypical pneumonia (Type C), severe pneumonia (Type D), or pneumonia in certain
      specific morbid states (Type E). Our objectives were to assess the actual use of
      antimicrobials and to determine the usefulness of the "Guidelines on Respiratory
      Infections--Basic Concepts in the Medical Care of Community-Acquired Pneumonia in
      Adults", developed by the Guideline-Drafting Committee of the Japanese
      Respiratory Society (JRS), in differentiating these categories of patients. We
      also hoped to elicit constructive opinions that would contribute to future
      revisions of these guidelines. The findings showed that pneumonia was classified
      as "bacterial pneumonia in which the causal organism was unknown" in
      approximately half (50.2%) of the patients studied. The next most common
      classification was "severe pneumonia", followed by "atypical pneumonia",
      "bacterial pneumonia in which the causal organism was presumed", and "pneumonia
      in certain specific morbid states", in that order. Our results suggest that the
      JSR guidelines, including the methods for differentiating between bacterial
      pneumonia and atypical pneumonia, are useful and appropriate, and that
      antimicrobial agents were generally selected in accordance with the guidelines.
      We also identified a number of issues to be addressed in future updates of the
      guidelines, including criteria for physiological assessment, handling of cases in
      which physical findings and laboratory test results are not in agreement, age
      related issues (especially the treatment of patients 65 years of age and older),
      the differentiation between bacterial pneumonia and atypical pneumonia, the
      weighing of underlying diseases and complications, and guidelines regarding the
      use of adjuvant therapy.

PMID- 14661551
TI  - [Long-term outcome of patients treated by home mechanical ventilation].
AB  - To investigate the long-term survival of 95 patients treated by home mechanical
      ventilation, we prospectively analyzed the outcomes of their cases (treatments:
      34, tracheostomy; 61, non-invasive methods) using the database of the local
      registration system in Aichi Prefecture. The annual actuarial probability of
      continuing home mechanical ventilation for the tracheostomized patients was 97.0%
      in the first year, 79.0% in the second year, 79.0% in the third year, and 69.2%
      in the fourth year, and those for the patients treated by non-invasive
      ventilation were 85.6%, 67.9%, 56.8%, and 46.4%, respectively. In comparison with
      patients with neuromuscular disease, patients with respiratory disease (both
      tracheostomized and non-tracheostomized) tended to show a lower continuation
      ratio, but the difference was not statistically significant. These data were
      comparable to those of previous reports, suggesting that home respiratory care in
      Aichi Prefecture satisfied the normal standards of quality.

PMID- 14661552
TI  - [A rare case of hemothorax due to rupture of an arteriovenous fistula: successful
      treatment by enucleation].
AB  - Hemothorax due to a rupture in an arteriovenous fistula is rare. We report a case
      in a 26-year-old woman who presented with continuous right chest pain. On
      admission, chest radiography revealed a nodular shadow in the right lower lung
      field with right pleural effusion. The pleural effusion aspirated was blood,
      suggesting a hemothorax due to the rupture of a pulmonary arteriovenous fistula.
      The shunt between A 8 and V 8 was confirmed in pulmonary arteriograms. A
      photomicrograph of the resected specimen showed a dilated arteriovenous fistula,
      part of whose inner wall was abnormally thin. The pleural wall surrounding the
      fistula was hypertrophic in parts, suggesting possible repetitive inflammation
      related with the rupture. Although transcatheter embolization is useful in the
      treatment of arteriovenous fistulae, it is technically difficult, and cases of
      fatal complications have been reported. While surgical resection is the most
      reliable treatment available, the present patient was already at high risk of
      dying. Accordingly, we chose to perform enucleation, and this was successful.

PMID- 14661553
TI  - [Bronchial artery embolization can be effective for primary racemose hemangioma].
AB  - We report two cases of primary racemose hemangioma in patients with hemoptysis.
      In the first, a 59-year-old man had a pulsatile polypoid lesion in the bronchus
      of the lingula; and in the second, a 24-year-old woman had a nodule in the
      bronchus of the right lower lobe. In both patients, arteriography of the
      bronchial artery revealed enlargement and convolution of its branches. Primary
      racemose hemangioma was diagnosed in both patients. The arteriography also
      revealed a shunt between the pulmonary and bronchial arteries in the woman.
      Bronchial artery embolization (BAE) was an effective treatment for the
      hemoptysis. To date, eight months after the embolization, hemoptysis has not
      recurred. Bronchoscopy and arteriography of the bronchial artery are both useful
      for diagnosing primary racemose hemangioma. BAE seems to be effective in treating
      primary racemose hemangioma.

PMID- 14661554
TI  - [A case of bronchial arterial aneurysm associated with recurrent massive
      hemoptysis].
AB  - A 69-year-old man was admitted to our hospital because of massive hemoptysis.
      Bronchial arteriography showed no abnormal findings. Bronchoscopic findings
      revealed a small, reddish elevated lesion on the posterior surface of the left
      upper lobe bronchus. Since the patient developed massive hemoptysis four times in
      a month, he underwent ligation and transection of the left bronchial artery, and
      bronchoplasty. Histopathologically, the resected tissue showed a bronchial
      arterial aneurysm without any inflammatory changes. We concluded that the
      aneurysm had developed in a malformed vessel.

PMID- 14661555
TI  - [Severe community-acquired Acinetobacter pneumonia].
AB  - A 62-year-old man with atrial fibrillation, hypertension, and fatty liver was
      admitted to a hospital in October 2002 complaining of productive cough and fever
      up to 38 degrees C for 2 days. He was a heavy smoker and drank alcohol regularly.
      He was dyspneic at rest, and chest radiography showed lobar pneumonia in the
      right upper lobe. Despite the administration of antibiotics, his condition
      deteriorated rapidly, and he was transferred to our hospital on the next day. On
      admission, he had multi-lobar pneumonia, septic shock, and disseminated
      intravascular coagulation. Despite the ventilatory support and the administration
      of carbapenem, macrolides, and catecholamine, he died 9 hours after admission.
      Later, all cultures from sputum and blood grew Acinetobacter species. Although
      community-acquired Acinetobacter pneumonias are rarely reported in Japan,
      physicians must be aware of this disease because of its fulminant clinical course
      and high mortality.

PMID- 14661556
TI  - [A case of metastatic lung tumor from an occult thyroid oncocytic carcinoma
      growing into the bronchial lumen].
AB  - We report a case of a metastatic lung tumor from an occult thyroid oncocytic
      carcinoma, growing into the bronchial lumen. A 70-year-old woman was referred to
      our hospital because of abnormal shadows which had been increasing in size for 4
      years, in the chest radiograph. Bronchoscopy revealed an endobronchial tumor at
      the orifice of the left B4b. Histological and immunohistological examination of
      the lesion showed tumor cells with immunoreactivity for thyroglobulin, and a
      metastatic oncocytic carcinoma from the thyroid was diagnosed. Closer examination
      of the neck revealed thyroid carcinoma, and total thyroidectomy was performed.
      Endobronchial metastasis of thyroid oncocytic carcinoma is very rare. In this
      case, immunohistological examination was useful for detecting the primary site.

PMID- 14661557
TI  - [Hypersensitivity pneumonitis induced by Pleurotus eryngii spores--a case
      report].
AB  - A 52-year-old man was hospitalized because of recurrent fever, dyspnea and cough
      in February 2002. He had worked in a Eringi (Pleurotus eryngii) mushroom factory
      since 1996. Chest radiography showed diffuse fine nodular shadows. Chest computed
      tomography demonstrated centrilobular nodules and increased attenuation in both
      lungs. The patient suffered from hypoxemia (PaO2 = 65 torr) while breathing room
      air. The lymphocyte count in the bronchoalveolar lavage fluid was increased, and
      transbronchial lung biopsy specimens showed lymphocyte alveolitis with
      epithelioid cell granulomas in the alveolar spaces. After admission, the
      patient's symptoms improved rapidly without medication. However, on his return to
      work, fever and hypoxemia appeared again. The lymphocyte stimulating test was
      positive against extracts of Eringi spores. Precipitins against the extracts of
      Eringi spores were detected by the double immunodiffusion test. Our diagnosis was
      hypersensitivity pneumonitis (HP) caused by Eringi spores. In Japan, more than 30
      cases of HP induced by mushroom spores have been reported. It is a matter of
      great urgency to prevent the occurrence of occupational HP in mushroom factories.

PMID- 14661558
TI  - [A case of the limited from of Wegener's granulomatosis without c-ANCA].
AB  - A 46-year-old woman was admitted to our hospital because of fever, cough and
      headache in December 2001. Although she had been treated for nasal obstruction
      and epistaxis by an otorhinolaryngologist in our hospital since 1996, no accurate
      diagnosis had been made despite repeated biopsies of the nasal mucosa. A chest CT
      taken in 1999 showed ground-glass opacities in both upper lobes. On admission,
      chest radiography and CT showed mass shadows without cavitation, corresponding to
      the lesions causing the ground-glass opacities. In addition, paranasal sinus MRI
      showed a deformity of the nasal septum accompanied by a space-occupying lesion,
      suggesting Wegener's granulomatosis. However, the cytoplasmic-antineutrophil
      cytoplasmic antibody (c-ANCA) test was negative. To achieve a definitive
      diagnosis, we performed an open lung biopsy. The specimen, obtained from the
      right upper lobe, showed the typical findings of a Wegener's granulomatosis
      including necrotizing vasculitis. Oral prednisolone treatment initiated at 20 mg
      daily, combined with oral cyclophosphamide at 50 mg daily markedly improved not
      only the clinical symptoms, but also the mass shadows in the left upper lobe.
      Patients with the limited form of Wegener's granulomatosis are occasionally
      seronegative and respond well to therapy. However, the natural course and the
      changes in chest radiographs are not understood well in such cases. In this
      paper, we report a case of the limited form of Wegener's granulomatosis that
      progressed slowly over a period of 6 years.

PMID- 14661559
TI  - [A case of severe Chlamydia pneumoniae pneumonia requiring mechanical ventilation
      and complicated with disseminated intravascular coagulation].
AB  - A previously healthy 48-year-old man presented to his primary care physician with
      high fever, dry cough and dyspnea. Pneumonia was diagnosed and intravenous
      administration of imipenem/cilastatin was begun, but his respiratory condition
      worsened and he was admitted to our hospital with severe hypoxia. A chest
      radiograph showed reticular opacity and consolidation in both lung fields. The
      case was complicated with disseminated intravascular coagulation. Analysis of the
      bronchoalveolar lavage fluid showed increases in the total cell counts and an
      elevated percentage of lymphocytes. Sputum, blood and bronchoalveolar lavage
      examinations failed to reveal etiology to explain his severe respiratory illness.
      Treatment consisted of mechanical ventilation and administration of steroid pulse
      therapy and gabexate mesilate. On the basis of his clinical course, we suspected
      possible atypical pneumonia, and began therapy with intravenous minocyclin and
      oral erythromycin administration. On the third hospital day, the arterial blood
      gas data improved and the bilateral pulmonary infiltration on the chest
      radiographs disappeared. Using paired sera, we detected increases of 1.35 in ID
      for anti-Chlamydia pneumoniae IgG antibodies by ELISA, and arrived at a diagnosis
      of Chlamydia pneumoniae pneumonia.

PMID- 14661560
TI  - [A case of multiple myeloma presenting as giant chest wall tumors with
      calcification].
AB  - A 60-year-old man was admitted for investigation of an abnormality detected in
      chest radiography: a giant tumor with calcification in the right middle lung
      field. A computed tomography (CT) scan revealed multiple tumors with
      calcification on the posterior chest wall. Histological analysis of the tumor
      specimen obtained by surgical biopsy demonstrated an increasing number of plasma
      cells accompanied with the deposition of amyloid. A bone marrow biopsy contained
      over 50% of plasma cells. We therefore diagnosed these tumors as multiple
      myeloma. It has been reported that multiple myeloma is usually characterized by
      osteolytic lesions; osteosclerotic changes are rare. Multiple myeloma should be
      taken into account as one of the causes of a chest wall tumor even if it is
      diffusely calcified.

PMID- 14661561
TI  - [Ionic strength influences hemolytic action of dibucaine hydrochloride].
AB  - BACKGROUND: Little is known about effect of ionic strength on local anesthetic
      toxicity. Using human erythrocytes, hemolytic action of dibucaine in solutions of
      various ionic strength was investigated. METHODS: The critical micellar
      concentration (CMC) of dibucaine and the dibucaine level that causes destruction
      of half of the red blood cells in vitro (EC50 value) were determined in solutions
      of various ionic strength. RESULTS: The mean CMC values of the dibucaine
      solutions adjusted to ionic strength 0.15, 0.30, 0.45 and 0.90 with NaCl, were
      35.3, 22.6, 15.9 and 9.6 mM, respectively. The mean EC50 values of these
      solutions measured at 5 sec were 22.5, 16.0, 12.6 and 8.2 mM, respectively, and
      those at 30 min were 4.9, 4.5, 4.5 and 2.6 mM, respectively. There was a
      significant correlation between mean CMC values and mean EC50 values at 5 sec but
      not at 30 min in the solution of the same ionic strength. CONCLUSIONS: These
      findings indicated that the mechanism of dibucaine-induced hemolysis within a few
      seconds is through membrane lysis, whereas dibucaine-induced hemolysis at 30 min
      is caused by another mechanism. Because each mechanism is enhanced by high ionic
      strength, dibucaine dissolved in salt solution should not be administered
      intrathecally.

PMID- 14661562
TI  - [Study of nausea and vomiting accompanying intravenous patient-controlled
      analgesia with fentanyl after cervical spine surgery].
AB  - BACKGROUND: Serious side effects of postoperative analgesia with opioid drugs
      include nausea and vomiting. METHODS: We investigated the effects of various
      factors (patient background, anesthesia duration, and intraoperative drug use) on
      the frequency and degree of postoperative nausea and vomiting (PONV) during the
      first 24 hours of intravenous patient-controlled analgesia (PCA) with fentanyl.
      RESULTS: PONV occurred in 34% of the male patients and 68% of the female, and in
      31% and 58% of smokers and non-smokers, respectively. CONCLUSIONS: Consideration
      should be given to gender and smoking status prior to starting preventive
      antiemetic therapy using PCA with fentanyl following cervical spine surgery.

PMID- 14661563
TI  - [Comparison of analgesic effects of intravenous flurbprofen and suppository
      indomethacin after laparoscopic cholecystectomy].
AB  - BACKGROUND: Epidural analgesia may not be necessary after laparoscopic
      cholecystectomy, but analgesics, such as non-steroidal anti-inflammatory drugs,
      may often be required postoperatively. There have been only a few studies
      comparing different NSAIDs in this situation. METHODS: After laparoscopic
      cholecystectomy under general anesthesia using intravenous propofol, nitrous
      oxide and fentanyl 3 micrograms.kg-1, 40 patients were randomly allocated to
      receive either intravenous flurbprofen 50 mg or suppository indomethacin 50 mg.
      Visual analogue scales of postoperative pain at 0, 10, 20, 30 and 60 min after
      surgery (at rest and at coughing), use of rescue analgesics, and the presence or
      absence of complications were recorded. RESULTS: Pain score at rest was markedly
      reduced (> 15% reduction from the baseline value) in 13 of 20 patients after
      injection of flurbiprofen and in five patients after indomethacin during the
      initial 60 min after surgery (P < 0.05), whereas there was no significant
      difference between the two groups for the pain score during coughing. There was
      no difference in the need of rescue analgesics within the initial 60 min, but the
      flurbiprofen group required significantly more rescue analgesics than the
      indomethacin group during 1-24 h after surgery (P < 0.005). The incidence of
      complications was low in both groups. CONCLUSIONS: Compared with suppository
      indomethacin, intravenous flurbiprofen is more effective in acute postoperative
      pain but the duration of its analgesic effect is shorter.

PMID- 14661564
TI  - [Blood lactate levels during fast-track cardiac anesthesia].
AB  - BACKGROUND: Lactate is a very sensitive marker of outcomes in critically ill
      patients. The aim of this study was to investigate the significance of blood
      lactate measurement during fast-track cardiac anesthesia. METHODS: We examined
      arterial blood lactate levels of 12 patients following coronary artery bypass
      graft surgery under intermittent aortic cross clamping with fast-track cardiac
      anesthesia. Anesthesia was induced with propofol and fentanyl, and maintained
      with propofol, fentanyl (total 400-1000 micrograms) and isoflurane. Blood samples
      were collected from a radical artery catheter. RESULTS: At the termination of the
      extracorporeal circulation, the blood lactate was 10.3 +/- 2.0 (7.4-12.5) mmol.l
      1. This value decreased slowly to 1.5 +/- 0.4 mmol.l-1 on the second
      postoperative day. All patients were extubated within 4 hours after surgery.
      Vital signs were stable, and no cardiac events occurred perioperatively.
      CONCLUSIONS: A continuous decline in blood lactate levels was related to a
      favorable postoperative course. Further research might be required to prevent
      transient hyperlactecemia at the end of cardiopulmonary bypass.

PMID- 14661565
TI  - [Massive bleeding due to hyperfibrinolysis during living-related liver
      transplantation for terminal liver cirrhosis; report of two cases].
AB  - We reported two cases of massive bleeding due to critical hyperfibrinolysis
      during living-related liver transplantation (LRLT) for end stage liver cirrhosis.
      The total volume of bleeding amounted to 57930 ml with the case 1, and amounted
      to 55980 ml with the case 2. TEG was useful for diagnosis of the
      hyperfibrinolysis. We administrated large amounts of FFPs, MAPs, PLTs, and
      gabexate mesilate. By rapid transfusion, we could manage to finish the procedures
      without hypotension, and complications were not observed at the early
      postoperative stage. We thought that the cause of the hyperfibrinolysis is the
      increasing blood tissue plasminogen activator (t-PA) due to long-anhepatic stage
      and small graft size. During anesthesia, since the functional start of a
      transplant liver is indispensable to it, in order to support a transplant liver
      for an improvement of hyperfibrinolysis, it is important to keep the homeostasis,
      such as body temperature, blood pressure.

PMID- 14661566
TI  - [Comparison of requirement for postoperative analgesics after inhalation and
      total intravenous anesthesia].
AB  - BACKGROUND: We evaluated the requirement for postoperative analgesics in 88
      patients undergoing abdominal total hysterectomy with inhalation anesthesia or
      with total intravenous anesthesia. METHODS: Anesthesia was induced in the
      inhalation anesthesia (GOS, n = 52) group with propofol and fentanyl, and
      maintained with sevoflurane, nitrous oxide balanced with oxygen, and additional
      administrations of fentanyl up to 0.2 mg in total. The patients in the total
      intravenous anesthesia (TIVA, n = 36) group were managed with target controlled
      infusion for propofol and intermittent administration of fentanyl. Effect site
      concentrations of fentanyl at the end of surgery were calculated using a
      pharmacokinetic-pharmacodynamic model. We divided the postoperative time course
      and evaluated the types, dosages, and prescription times of postoperative
      analgesics in each. RESULTS: Both total dosage and effect-site concentration of
      fentanyl were higher in the TIVA group than in the GOS group, and total
      prescription time in the TIVA group was significantly less during the 24 hrs
      after the operation. Supplemental prescription intervals of buprenorphine were
      significantly less in the TIVA group. Since administration of fentanyl during
      operation was adequate, patients in the TIVA group were considered to be in a
      sufficient analgesic state at the end of operation. CONCLUSIONS: The
      postoperative pain can be reduced with TIVA.

PMID- 14661567
TI  - [Nicorandil reduces incidence and severity of pain on propofol injection].
AB  - BACKGROUND: Propofol is commonly used for induction and maintenance of
      anesthesia, but the pain during injection of propofol remains a clinical problem.
      We studied whether nicorandil prevents the pain on propofol injection. METHODS:
      The study was conducted in 120 adult patients scheduled for elective surgery. The
      patients were assigned to two groups; Group C (n = 60) received bolus injection
      of propofol alone; Group N (n = 60) received bolus injection of 2 mg of
      nicrorandil 3 minutes before propofol injection, and followed by continuous
      nicorandil infusion at a rate of 6 mg.h-1. The pain on injection was assessed as,
      none, mild, moderate, or severe at 15-second intervals. RESULTS: The incidence of
      propofol-induced pain was significantly higher in Group C (77%) than in Group N
      (30%) (P < 0.05). The severity of pain was significantly higher in Group C than
      in Group N (P < 0.05). CONCLUSIONS: Nicorandil reduces the incidence and severity
      of pain on propofol injection.

PMID- 14661568
TI  - [Successful airway management using a Cook airway exchange catheter as an
      emergent dilator for life-threatening neoplastic stenosis of the trachea: a case
      report].
AB  - A 68-year-old male patient was referred to our hospital for his intractable and
      progressive dyspnea. Chest roentgenography and computerized tomography revealed
      severe lower tracheal stenosis due to neoplastic invasion. The tumor completely
      surrounded his trachea for 5 cm length and the remaining internal diameter of the
      trachea was less than 5 mm. To avoid fatal asphyxia, emergency airway security
      was required. After placing both femoral arterial and venous cannulae for
      percutaneous cardiopulmonary support system, we dilated the stenotic trachea
      using a Cook airway exchange catheter (CAEC), and then an armored tube of 7 mm
      inner diameter was introduced through the CAEC. The maneuver was smoothly
      completed within one minute without any complications. His dyspnea was completely
      relieved. Following chemotherapy and radiotherapy were so effective that the
      endotracheal tube was extubated two weeks later uneventfully. After several
      series of chemotherapy and 50 Gy irradiation, the patient was discharged three
      months later without symptoms. We concluded that CAEC could be one of the life
      saving instruments for emergent airway management in case of severe organic
      tracheal stenosis.

PMID- 14661569
TI  - [Airway obstruction in a patient using a cuff button-like silicone cannula for
      tracheal stoma].
AB  - We described a case of postoperative airway obstruction in a patient using a cuff
      button-like silicone cannula for tracheal stoma. A 59-year-old woman with
      rheumatoid arthritis, was admitted to the hospital for total knee arthroplasty.
      She had been managed by a long-term tracheostomy for rheumatic cricoarytenoid
      arthritis. Preoperative examination revealed no cardiopulmonary compromise. The
      surgery was performed under combined spinal-epidural anesthesia without any
      respiratory problems. Fifteen hours after surgery, she complained of dyspnea. Her
      oxygen saturation by pulse oximeter was 22-28%. We immediately removed the
      silicone cannula and inserted a tracheostomy tube. Her condition was dramatically
      improved next few minutes after the insertion. There were no dyskinesia and
      neurological disorders. We considered that airway obstruction occurred with the
      inadequate position of the cuff button-like silicone cannula, attached to the
      posterior wall of the trachea, sputum augmenting the obstruction.

PMID- 14661570
TI  - [Changes in cytokines during perioperative period of hip arthroplasty in patients
      older than 80 years of age].
AB  - BACKGROUND: Elevations of plasma inflammatory cytokines are related to the
      surgical intervention. We have examined the circulating interleukin 6, 8 (IL-6,
      IL-8) and CRP responses in patients older than 80 years during orthopedic hip
      arthroplasty. METHODS: After taking the signed informed consent, 8 patients were
      enrolled in this study. All patients received standard spinal anesthesia combined
      with epidural catheterization. Samples were collected just before and after the
      surgery, and on 1st, 2nd and 7th day after the operation. RESULTS: Plasma IL-6
      levels showed a significant increase on the day after surgery (5.6 +/- 3.7 vs.
      52.2 +/- 24.1 pg.ml-1, mean +/- SD, P < 0.05), whereas although the levels of IL
      8, increased (minimum 7.9 +/- 3.2 to maximum 70.3 +/- 80.2 pg.ml-1, mean +/- SD),
      the change was not significant. CRP levels were slightly elevated in the
      preoperative examination (2.8 +/- 3.5 mg.dl-1) and further increased on the 2nd
      day of surgery (8.3 +/- 5.4 mg.dl-1), but returned to a normal level on the 7th
      day. CONCLUSIONS: From the viewpoint of cytokines, this study showed that,
      although IL-8 level did not return to the preoperative value, the surgical stress
      of orthopedic hip arthroplasty in patients older than 80 years was almost of the
      same level as reported previously.

PMID- 14661571
TI  - [Obstruction of an reinforced endotracheal tube due to dissection of internal
      tube wall during total intravenous anesthesia].
AB  - We report here a case of obstruction of an reinforced endotracheal tube during
      laryngomicrosurgery under total intravenous anesthesia. In this case, we used a
      6.0 mm ID reinforced endotracheal tube that had been used previously for other
      patients and sterilized two times by ethylene oxide gas. During the operation,
      the peak airway pressure increased gradually and eventually reached to 35 cmH2O.
      After the exchange of the endotracheal tube, ventilation was improved
      immediately. The endotracheal tube was occluded by dissection of internal wall.
      Several cases of reinforced tube obstruction have already been reported and in
      most of these cases the obstruction was related to their repeated use and nitrous
      oxide anesthesia. However, the present case showed that dissection of reinforced
      endotracheal tube could also occur during general anesthesia without using
      nitrous oxide. We should bear in mind that repeated use of reinforced
      endotracheal tube could induce a critical airway obstruction.

PMID- 14661572
TI  - [A case of dissociative stupor with decorticated posture after neck clipping of
      brain aneurysm].
AB  - We experienced a case of dissociative stupor with decorticated posture in a 71
      year-old woman after neck clipping of the brain aneurysm. Decorticated posture is
      observed with severe midbrain disorder caused by brain herniation. In this case,
      therefore, severe brain stem damage was suspected, although light reflex was
      observed and respiration was stable. In addition, in this case, the aneurysm was
      located at the junction of the internal carotid artery and the posterior
      communicating artery. Therefore, surgical damage to midbrain was not likely to
      have happened. Postoperative computed tomography showed no abnormality in this
      region. Two days later, her symptom disappeared, and she could clearly recollect
      memory of these two days just after surgery. However, she could not follow
      directions because of a sense of fear. Thus her symptom might be based on a kind
      of mental disorder. Patients with conversion disorder react abnormally to
      stimulus or stress. Stupor was diagnosed as due to defect of reaction to stimulus
      of sound, light and touch. She was diagnosed as dissociative stupor of the
      conversion disorder type. In this case, decorticated posture was caused by mental
      disorder. We have to pay attention not only to brain tissue damage but also to
      psychological damage of patients.

PMID- 14661573
TI  - [A case of nerve injury after vascular access surgery under brachial plexus
      block].
AB  - A 52-year-old woman underwent vascular access surgery under brachial plexus block
      of the left arm. After the surgery, the patient complained of painful and burning
      sensation and motor disturbance of her forearm without muscle necrosis. We
      administered ketamine to treat the symptoms as neuropathic pain arising as a
      complication of brachial plexus nerve block. Six days after operation,
      angiography showed little blood flow at distal portion of the shunt. We
      recognized ischemia induced monomeric neuropathy. Immediately after the occlusion
      of the vascular access, the pain disappeared but not sensory and motor
      disturbances. Our experience suggests that angiography is helpful for diagnosis
      of ischemia-induced neuropathy after vascular access surgery.

PMID- 14661574
TI  - [Postoperative pulmonary bleeding and reperfusion pulmonary edema in an adult
      patient after repair of tetralogy of Fallot with pulmonary atresia--percutaneous
      cardiopulmonary support (PCPS) and lung protective ventilatory strategy].
AB  - After total correction of tetralogy of Fallot, pulmonary atresia and major aorto
      pulmonary collateral arteries, a 31-year-old man developed life-threatening
      pulmonary hypertension and reperfusion pulmonary edema, leading to pulmonary
      hemorrhage, right heart failure and hypoxia. Because of difficulty in weaning
      from cardiopulmonary bypass and in controlling hemorrhage from pulmonary
      arteries, we applied percutaneous cardiopulmonary support (PCPS) for 281 hours
      with strategy of delayed sternal closure (17 days) and a large quantity of
      transfusion. We also applied lung protective ventilatory strategy for reperfusion
      pulmonary edema (high PEEP, limited peak inspiratory pressure and recruitment
      maneuver). As the result, he was discharged alive without any major
      complications. We report our postoperative managements, in terms of 1) lung
      protective ventilatory strategy, 2) surgical control of pulmonary blood flow, and
      3) evaluation of the cardiopulmonary function during PCPS for early weaning from
      PCPS.

PMID- 14661575
TI  - [Laparoscopic cholecystectomy under general anesthesia for a woman in the 28th
      week of gestation].
AB  - Anesthesia for laparoscopic cholecystectomy under hypobaric pneumoperitoneum was
      given to a pregnant woman in 28th week of gestation. Anesthesia was induced by
      administering thiopental(5 mg.kg-1) and vecuronium (0.1 mg.kg-1). The lungs were
      artificially ventilated with oxygen, nitrous oxide, and low concentrations of
      sevoflurane to maintain the end-expiratory CO2 pressure at 30 to 35 mmHg. Before
      inducing anesthesia, a thoracic epidural catheter was inserted, and 2%
      mepivacaine was administered through the catheter. During the operative period,
      the operating field was secured by the pneumoperitoneum pressure at 8 mmHg and
      Fowler's and left down position. Mother's blood gases and the fetal heart beat
      monitored with the abdominal supersonic wave stayed steady through the
      perioperative periods. The pneumoperitoneum time was 34 minutes and the operation
      time was 40 minutes without any troubles. But we should pay much attention to
      anesthesia and operation in any pregnant patient.

PMID- 14661576
TI  - [Anesthetic management for a radical operation in an infant with cloacal
      exstrophy].
AB  - We report the anesthetic management for a radical operation in an infant with
      cloacal exstrophy. Diagnosis of cloacal exstrophy with meningocele was made at
      the 26th week of gestation. Cesarian section was performed under general
      anesthesia in order to keep the infant in a state of apnea to prevent aerophagia,
      the so-called "sleeping baby", at the 38th week of gestation. As soon as the
      infant was born, she was intubated orotracheally and a radical operation
      (abdominal closure, removal of meningocele, and vesico-intestinal-pelvioplasty)
      was performed. Some complications occurred during the operation including
      hypotension, oliguria, hypothermia, hypoproteinemia, hyponatremia and
      hyperpotassemia. The operation time was 10 hours and 30 minutes. Mechanical
      ventilation was continued for 4 days in the NICU and the infant was discharged 37
      days after the operation. Early prenatal diagnosis and simulation of the
      operation enabled an effective surgical procedure allowing us to minimize these
      intraoperative complications.

PMID- 14661577
TI  - [Anesthetic management of a patient with Smith-Lemli-Opitz syndrome complicated
      with thrombocytopenia].
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome,
      characterized by severe growth failure and congenital anomalies (for example
      dysgenesis, mental retardation, renal and cardiac defects, and various
      malformation). SLOS results from error of a cholesterol enzyme and generalized
      cholesterol deficiency. This report describes our experience of a patient with
      SLOS and thrombocytopenia who underwent anesthesia twice for surgical procedures
      in a year. The patient received drip platelet transfusion for thrombocytopenia
      before operations. Anesthesia was induced with inhalation of oxygen, nitrous
      oxide and sevoflurane, and maintained with oxygen, propofol, fentanyl and low
      concentrations of sevoflurane. Airway was maintained with laryngeal mask airway.
      Complications were not seen in this case. One of the problems in anesthetic
      management of SLOS is difficult intubation because of the typical dysmorphic
      facial features such as micrognathia, cleft palate and abnormal tongue. We
      thought that laryngeal mask airway was useful and safe for SLOS patients. Two
      cases of malignant hyperthermia were reported in anesthetic management of SLOS by
      using halothane or suxamethonium. In this case, the anesthetic maintenance was
      mostly with propofol and fentanyl. Malignant hyperthermia did not occur but
      sevoflurane was used at low concentrations. SLOS presents various problems with
      anesthetic management and we have to administer general anesthesia carefully.

PMID- 14661578
TI  - [The cracks of polycarbonate three-way stopcocks are enhanced by the lubricating
      action of fat emulsion of propofol].
AB  - The possible mechanism of cracks in the polycarbonate three-way stopcocks was
      investigated in the presence of propofol. We compared the crack formations with
      various insertion force and contact surface conditions. We could successfully
      reproduce overt cracks with leakage in three-way stopcocks when the male adaptors
      were strongly inserted and the contact surface was damped with propofol. With
      normal strength, no overt crack was observed at any liquid contact conditions.
      The male connector is more deeply inserted into the female three-way stopcock at
      the same insertion force when contact surface is damped with propofol. When
      propofol is present, the release force is not enhanced further while insertion
      force is increased. We conclude that the cracks in three-way stopcocks are
      enhanced by the increased expansion force by the lubricating action of propofol
      fat emulsion.

PMID- 14661579
TI  - [Overview: signal transduction and transcriptional controls].

PMID- 14661580
TI  - [Signal transduction and chromatin].

PMID- 14661581
TI  - [STAT: transcriptional regulator of cytokine signaling].

PMID- 14661582
TI  - [Transcriptional regulation by the transforming growth factor-beta signaling].

PMID- 14661584
TI  - [Xenobiotics and transcriptional regulation].

PMID- 14661583
TI  - [Gene cascade by hormonal control during development of insects].

PMID- 14661585
TI  - [Transcriptional control by nuclear receptors].

PMID- 14661586
TI  - [Engineered biosynthesis of plant polyketides].

PMID- 14661587
TI  - [Mechanism and evolution of the CCA-adding activity].

PMID- 14661588
TI  - [Statistical analysis of gene expression profiles].

PMID- 14661589
TI  - [A magic agent in protein refolding: arginine].

PMID- 14661590
TI  - [Editorial Board activities].

PMID- 14661591
TI  - [Opinion: Using Turkish in scientific literature].
AB  - Foreign vocabulary has long been used widely in the community life, education, as
      well as scientific activities including national meetings and publications in
      Turkey. Intrusion of English into Turkish medical and radiological literature has
      been increasingly more prevalent in the recent decades. This challenge has to be
      dealt with on every platform and with a national concensus. Radiology societies
      and radiology journals must play a pivotal role in the elimination of foreign
      terms from the national radiology literature and their replacement with Turkish
      nomenclature.

PMID- 14661592
TI  - [Radiologic investigation of vertebrobasilar insufficiency and quantification of
      vertebrobasilar flow with magnetic resonance imaging].
AB  - PURPOSE: To evaluate the contribution of cervical spine radiograms, Doppler US,
      cervical and cranial MRI, MRA and two dimensional quantification flow in the
      diagnosis of vertebrobasilar insufficiency. MATERIALS AND METHODS: We
      prospectively examined 25 patients having signs of vertebrobasilar insufficiency
      (16 females and 9 males, aged 34 to 74 years) and 25 controls of the same age and
      sex with MRI, MRA, Doppler US and cervical radiograms. Cervical spine radiograms
      were evaluated for the presence of degenerative changes, osteophytes and loss of
      height. The flow velocities of the basilar artery and vertebral arteries were
      measured with two dimensional quantification flow, using time-velocity graphics
      achieved by means of a region of interest drawn on transverse sections of the
      vessels. Posterior circulation in farcts and slow flow in vertebrobasilar system
      arteries were investigated on brain MR images and the presence of cervical
      osteophytes, spinal cord compression and the effect of the presence of
      degenerative changes on vertebral arteries were evaluated on cervical MR images.
      Paired samples T-test, independent samples T-test, Wilcoxon W, Mann-Whitney U and
      chi-square tests were used for statistical analysis. The significance level was
      taken at p below 0.05. RESULTS: From the statistical analysis, we found that
      there were more pathologic findings on MRA within the patient group compared with
      the controls (p = 0.002). The velocities measured by MRI were significantly
      affected by the presence of unknown bright objects on brain MR images,
      osteophytes on cervical MR images, loss of height and the presence of osteophytes
      on radiograms in patients having VBI signs, when compared to the controls. In
      both groups, the measurements of flow velocity in vertebral arteries by Doppler
      US did not correlate with the measurements by two dimensional quantification
      flow. CONCLUSION: Among the methods we used in our study, MRA was the most
      specific in the diagnosis of patients with vertebrobasilar insufficiency.
      However, two dimensional quantification flow can be used as a noninvasive but
      indirect method to investigate the influence of several factors on the
      hemodynamics.

PMID- 14661593
TI  - [Functional magnetic resonance imaging in lesions in or near the sensorimotor
      cortex].
AB  - PURPOSE: To assess the efficiency of functional magnetic resonance imaging (fMRI)
      in demonstrating motor-sensorial cortical areas in mass lesions neighboring the
      perirolandic area and investigating its pre-operative sensitivity. MATERIALS AND
      METHODS: In the study, 20 right-handed patients with different types of intraxial
      and extraaxial mass lesions in or neighboring the perirolandic area were used. Of
      the all lesions, 6 were diagnosed as metastatic masses, 2 as oligodendroglioma, 2
      as astrocytoma, 5 as glioblastoma multiforme, 2 as meningioma, 2 as arteriovenous
      malformations and 1 as porencephalic cyst. The study was performed on a 1.5 T
      unit. Images were acquired at the axial plane using T1 weighted spin echo, T2
      weighted fast spin echo and fast FLAIR. Functional imaging was performed by blood
      oxygen-level-dependent (BOLD) technique and single-shot gradient echo-planar
      sequence (SSEPI). During the sequence period a total of 420 images were acquired,
      each of which had 10 slices. By matching the resource functional images with T1
      and T2 weighted anatomical images, the functional anatomy of the brain has been
      mapped. Sensorial-motor cortex has been activated by the finger-tapping-paradigm.
      RESULTS: Two patients could not included in the study because of extensive
      movement artifacts and meaningless BOLD answers. Eighteen of the patients had
      significant BOLD answers in bilateral peri-central sulcal area and in the center
      of the supplementary area. Activation areas were obtained neighboring the mass
      lesions and edema surrounding the lesion. CONCLUSION: fMRI can demonstrate motor
      sensorial cortex in situations in which the anatomical order of perirolandic area
      has been changed by mass lesions. fMRI shows high sensitivity in the evaluation
      of lesions neighboring the perirolandic area preoperatively. Therefore fMRI can
      provide important information in patient selection, detection of different
      surgical choices and planning the surgical intervention.

PMID- 14661594
TI  - [MRI features of adult tethered cord syndrome].
AB  - PURPOSE: Tethered cord syndrome is a congenital childhood disease, which can also
      be seen in adults. The aim of this study was to describe magnetic resonance
      imaging findings of 17 adult patients with tethered cord syndrome and correlate
      the magnetic resonance images with intraoperative findings. MATERIALS AND
      METHODS: Between 1994 and 2002, 57 patients with tethered cord syndrome were
      detected in the neurology and neurosurgery departments in our hospital. Seventeen
      of these patients were adults and included in this study. The male to female
      ratio was eleven to six. The mean age was 33.2 years. All patients had physical
      and neurological examinations and were evaluated with plain films and lumbosacral
      MRI. All patients underwent surgery and the intraoperative findings were
      correlated with MRI findings. RESULTS: MRI could delineate the localization of
      the conus, thickness of the filum terminale and other pathologic conditions.
      Thick-short filum terminale, diastematomyelia, intradural lipomas and
      lipomyelomeningoceles were the most common etiological factors. Conus terminalis
      terminated distal to the level of L2-L3 intervertebral disc space in all
      patients. Except two patients with thick-short filum terminale, MRI findings were
      same with the operative findings. Vertebral anomalies could be detected both with
      plain films and MRI scans. CONCLUSION: MRI is an excellent diagnostic tool in the
      diagnosis of tethered cord syndrome. Patients with persistent leg and back pain
      associated with sphincter problems should be evaluated with MRI for a possible
      tethered cord syndrome.

PMID- 14661595
TI  - [Multi-slice CT angiography in the diagnosis and characterization of cerebral
      aneurysms].
AB  - PURPOSE: To assess the diagnostic accuracy of multislice computed tomography
      angiography in the detection and characterization of cerebral aneurysms.
      MATERIALS AND METHODS: Multislice CT angiography and DSA were performed in 41
      patients suspected to have intracranial aneurysms. A volume rendering method was
      used to produce three-dimensional CT angiograms. The diameter, location, neck and
      branching pattern of aneurysms were evaluated with CT angiography and DSA and
      compared with each other. RESULTS: Of 41 patients, DSA depicted 44 aneurysms in
      33 patients. Multislice CT angiography depicted 44 aneurysms in 34 patients. One
      aneurysm demonstrated with DSA was not detected at multislice CT angiography. One
      aneurysm demonstrated with multislice CT angiography and confirmed at surgery was
      not demonstrated with DSA. There was no false positive aneurysm in multislice CT
      angiography. There were 4 aneurysms smaller than 3 mm and multislice CT
      angiography demonstrated all these aneurysms. In 9 aneurysms, the neck and
      branching pattern could only be shown with multislice CT angiography. Sensitivity
      and specificity of multislice CT angiography were 97.7% and 87.5%, respectively.
      CONCLUSION: Multislice CT angiography has a high sensitivity and specificity in
      the diagnosis of intracranial aneurysms and is superior to DSA in the delineation
      of the aneurysm neck and branching pattern. Multislice technology with
      submillimeter collimation improves the detection of small aneurysms and the
      delineation of the neck of the aneurysms.

PMID- 14661596
TI  - [Dynamic contrast-enhanced brain perfusion imaging: Technique, pitfalls and
      problems].
AB  - Conventional magnetic resonance and computed tomography imaging, despite their
      sensitivity in delineating tissue anatomy and detecting head and neck pathology,
      are nonspecific in their ability to physiologically characterize abnormal tissue.
      The perfusion imaging attempts to measure the steady-state delivery of blood to a
      given parenchymal region. In this article, the technique of magnetic resonance
      perfusion and computed tomographic perfusion is discussed in addition to the
      pitfalls and problems in the light of the latest literature and our own
      experience.

PMID- 14661597
TI  - [Comparison of low dose and standard dose CT in the evaluation of inflammatory
      diseases of paranasal sinuses].
AB  - PURPOSE: The aim of this study was to investigate the diagnostic value of low
      dose CT (LDCT) by comparing the identification of sinonasal anatomical
      structures, anatomic variations and detectability of inflammatory changes at low
      and standard dose CT (SDCT). MATERIALS AND METHODS: A total of 30 patients who
      were referred to CT scan for the assessment of paranasal sinuses underwent CT
      examinations at both standard [110 mA, 120 kV, 5 mm collimation (3 mm collimation
      at the level of the ostiomeatal unit)] and low dose [22 mA, 120 kV, 5 mm
      collimation (3 mm collimation at the level of the ostiomeatal unit)]. All images
      were photographed at identical window settings (window width, 4000 HU; window
      level, 50 HU) on laser film. Ten sinonasal anatomical structures (five on the
      right and five on the left) and inflammatory mucosal changes were recorded for
      each patient. The detectability and conspicuity levels were scored for each
      finding. RESULTS: A total of 297 sinonasal anatomical structures were identified
      at SDCT, whereas 296 structures were detected at LDCT. Inflammatory mucosal
      changes and anatomical variations were equally identified at both SDCT and LDCT
      (p > 0.05). There was no statistically significant difference between SDCT and
      LDCT in the detection on of anatomical structures, variations and inflammatory
      changes (p > 0.05). CONCLUSION: The low dose CT protocol used in this study
      provided images of adequate quality, and proved to be reliable in the evaluation
      of normal and diseased paranasal sinuses.

PMID- 14661598
TI  - [Diagnostic efficacy of low dose paranasal sinus CT examination].
AB  - PURPOSE: Investigation of the diagnostic efficacy of low dose paranasal sinus CT
      examination for decreasing the patient radiation dose. MATERIALS AND METHODS: A
      limited number of low dose CT sections (5 sections/patient; 30 mAs, n = 30; 60
      mAs, n = 30) were performed in addition to standard dose (200 mAs) coronal
      paranasal sinus CT examination in 60 patients. Previously determined anatomical
      structures (uncinate process, maxillary ostium, lamina papyracea, fovea
      ethmoidalis, nasolacrimal canal, ethmoidal infundibulum, ethmoidal bony septae)
      were scored in terms of detectability and sharpness in both low and standard dose
      images. The scores of low dose groups were assessed both totally and separately
      for each anatomical structure, and compared with scores of the standard dose
      group. Wilcoxon signed ranks test was performed for comparison of the scores.
      RESULTS: No significant difference was detected upon comparison of the 60 mAs
      group and the standard dose group. The diagnostic quality for the lamina
      papyracea, fovea ethmoidalis and ethmoidal bony septae were insufficient in the
      30 mAs-group compared with the standard dose group. The difference was
      statistically significant (p < 0.05). CONCLUSION: 60 mAs-low dose paranasal sinus
      CT examinations have sufficient diagnostic quality.

PMID- 14661600
TI  - [Bronchogenic cysts: Radiologic findings].
AB  - Bronchogenic cysts are congenital anomalies that result from abnormal budding of
      the tracheobronchial tree. They are usually found in the mediastinum around the
      tracheobronchial tree or in the lung parenchyma. Although they can occur in
      infants and children, they are frequently detected coincidentally in the third
      and fourth decades. Their radiological findings can change according to their
      locations. In this pictorial assay we reviewed the radiological appearance of
      bronchogenic cysts with different imaging modalities.

PMID- 14661599
TI  - [Evaluation of rhinorrhea by computed tomography cisternography].
AB  - PURPOSE: We aimed to emphasize the indication for and importance of CT
      cisternography in the diagnosis of rhinorrhea patients by reviewing the
      literature with the support of unenhanced cranial CT findings. MATERIALS AND
      METHODS: Unenhanced cranial CT with axial sections and CT cisternography with
      coronal sections were performed in 14 patients who had spontaneous (n = 3) and
      posttraumatic (n = 11), intermittent or continuous CSF rhinorrhea. The slice
      thickness of infratentorial planes was 5 mm and supratentorial planes 10 mm. CT
      cisternography was performed from nasion to dorsum sella with a 3 mm slice
      thickness and 3 mm intervals. Bony and/or dural defects with entry of contrast
      into the ipsilateral paranasal sinuses were accepted as positive results.
      RESULTS: A CSF fistula was determined in nine of eleven posttraumatic patients.
      Three of them had accompanying cerebral herniation while on had a
      pseudomeningocele. The etiology of two spontaneous rhinorrhea patients was shown
      to be empty sella and meningocele pouch respectively. Eleven patients (nine
      posttraumatic, two spontaneous) whose CSF fistula had been shown on CT
      cisternography were operated on and our findings were confirmed. CSF fistula or
      bony defect was not observed in the CT cisternography of 3 biochemically proven
      rhinorrhea patients (2 posttraumatic, 1 spontaneous). These 3 patients were
      clinically observed and their rhinorrhea ended spontaneously. One posttraumatic
      patient who had had 2 operations had recurrence of rhinorrhea with an infected
      extradural collection six months after the operation. Another posttraumatic
      patient developed meningitis before CT cisternography. CONCLUSION: CT
      cisternography should be the preferred examination method in rhinorrhea patients,
      since it is cheaper than MR cisternography, is a widely used scanning technique
      and reduces the risks of surgical recurrences by showing the exact location of
      the fistula.

PMID- 14661601
TI  - [Pancreas divisum: Diagnostic importance of MR cholangiopancreatography].
AB  - PURPOSE: Pancreas divisum, non-fusion of the ventral and dorsal pancreatic ductal
      system, affects up to almost 10% of the population. Approximately 20% of the
      patients with pancreas divilsum will develop complications such as recurrent
      pancreatitis. In this study, we aimed to present the magnetic resonance
      cholangiopancreatography (MRCP) findings of pancreas divisum, evaluate its
      frequency in our study group and illustrate the importance of MRCP in the
      diagnosis of this anatomic variation. MATERIALS AND METHODS: Between August 2000
      and October 2002, 248 patients suspected of having pancreatobiliary disease
      underwent MRCP with a 1.0 Tesla scanner. A phased-array coil was used for signal
      detection. Thirty-five to 70 millimeter thick slabs and thin (3 mm) collimation
      heavily T2 weighted images were obtained with the SSFSE (single shot fast spin
      echo) technique. Diagnosis of pancreas divisum was made by evaluation of the
      thick slabs, source and three dimensional reformatted images. RESULTS: Eleven of
      the patients with ages ranging from 23 to 71 years (mean: 55.8 +/- 4.2) were
      diagnosed as having the variation "pancreas divisum" (4.4%). Ten had symptoms of
      hepatobiliary disease and one showed signs of recurrent pancreatitis. All but
      three of the patients were correlated well with ERCP; in one patient ERCP could
      not be performed due to a cannulation problem secondary to Billroth II procedure
      and, in two patients ERCP was found to be unnecessary as MRCP was efficient. The
      patient having signs of pancreatitis was diagnosed as recurrent pancreatitis
      during the clinical diagnostic work-up. A dominant dorsal duct draining into
      minor papilla was detected in all patients, only five of them showed a short
      segment ventral duct in the pancreatic head region, while it was absent in the
      others. CONCLUSION: MRCP is a rapid and non-invasive method of evaluating the
      pancreatic ductal system. It helps in identifying pancreas divisum, which may be
      the cause of recurrent pancreatitis, and so obviates the need of ERCP.

PMID- 14661602
TI  - [The role of spiral CT in the preoperative evaluation of malignant gastric
      neoplasms].
AB  - PURPOSE: The purpose of this study was to evaluate the performance of spiral CT
      in preoperative staging in patients with gastric cancer. MATERIALS AND METHODS: A
      total of 28 patients with an established diagnosis of 24 gastric adenocarcinoma,
      2 gastric lymphoma, 1 carcinoid tumor, 1 leiomyosarcoma were evaluated with
      spiral CT for serosal invasion, pancreatic invasion, metastasis and peritoneal
      involvement. Results were compared with surgical and pathological staging.
      RESULTS: The accuracy of spiral CT in determining the depth of tumor invasion,
      pancreatic invasion, lymph node metastasis, peritoneal metastasis, liver
      metastasis and splenic metastasis were 82% (23/28), 96% (27/28), 82% (23/28), 96%
      (27/28), 100% (28/28) and 100% (28/28) respectively. The differentiation between
      T2-T3, T3-T4, N0-N1, N1-N2, N2-N3 were possible in 83% (15/18), 92% (23/25), 79%
      (15/19), 73% (8/11), and 89% (8/9). The accuracy of spiral CT in overall TNM
      staging of gastric adenocarcinomas was 67% (16/24). CONCLUSION: Spiral CT is an
      effective tool in the preoperative staging of gastric malignancies.

PMID- 14661603
TI  - [Case report: Radiologic findings of retroperitoneal malignant mesenchymoma].
AB  - Malignant mesenchymomas are rare soft tissue tumors that contain two or more
      distinct histologic subtypes of sarcoma within the same tumor. Although
      experience with these tumors is limited, they are generally considered high grade
      neoplasms and are associated with a poor prognosis. Here we present radiologic
      findings of a case with malignant mesenchymoma in the retroperitoneum.

PMID- 14661604
TI  - [A comparison of planar scintigraphy and MRI in the screening of skeletal
      metastases].
AB  - PURPOSE: In this study, we aimed to compare magnetic resonance imaging (MRI) and
      planar scintigraphy findings of patients with known or suspected skeletal
      metastases. MATERIALS AND METHODS: Twenty eight patients (13 women, 15 men)
      ranging from 35 to 63 years old, underwent whole body MRI with coronal plane
      turboSTIR sequence and Tc 99m methylene diphosphonate planar scintigraphy for
      detecting skeletal metastases. RESULTS: MRI showed metastases in 20 cases,
      whereas scintigraphy was positive in 23 cases. In 2 patients where scintigraphy
      showed 4 lesions, MRI showed them to be degenerative changes. In 3 patients
      scintigraphy showed 4 metastases that were not seen on MRI. In 7 patients
      extraskeletal metastases were identified by MRI alone. Statistical analysis
      showed exact correlation between both techniques (Mc Nemar p = 0.25). CONCLUSION:
      Our results suggest that whole-body MRI is as effective as scintigraphy in
      skeletal metastases. In the future, developments in MRI technology, increases in
      the number of MRI units and new studies may make MRI an alternative screening
      technique to scintigraphy.

PMID- 14661605
TI  - [Case report: MRI findings in gout].
AB  - MR imaging is not routinely used for the evaluation of tophaceous gout. However,
      gout may have atypical clinical and radiologic findings. It should be considered
      in the differential diagnosis when a mass reveals heterogeneous and low signal
      intensity on T2 weighted images. We present MR imaging characteristics of gout
      tophi and arthritis in two patients.

PMID- 14661606
TI  - [Percutaneous transluminal angioplasty in the prevention of bypass graft
      failure].
AB  - PURPOSE: To evaluate the results of percutaneous transluminal angioplasty in the
      prevention of bypass graft failure with dilatation of the anastomotic and
      perianastomotic obstructions following surgery. MATERIALS AND METHODS: Fourteen
      proximal or distal anastomotic/perianastomotic obstructions in one illiofemoral,
      one aortofemoral and ten femoropopliteal bypass grafts in eleven patients were
      diagnosed by clinical examination, Doppler ultrasonography, intravenous and
      intraarterial DSA in a follow-up period of 4-24 months after surgery.
      Percutaneous transluminal angioplasty was attempted in these anastomotic or
      perianastomotic lesions including two occlusions. RESULTS: Percutaneous
      transluminal angioplasty was successful for all cases. In a follow-up period of 4
      45 months, eight patients remained asymptomatic with patient grafts. In one
      patient, the graft was occluded in the fourth month. In two others, restenosis
      occurred at the seventh and seventeenth months and required redilatation.
      Cumulative primary patency rate for one year was 92 +/- 6.8%. CONCLUSION:
      Percutaneous transluminal angioplasty is an effective alternative treatment
      modality for anastomotic and perianastomotic bypass graft-related obstructions
      and may enhance the overall graft patency.

PMID- 14661607
TI  - [Percutaneous mechanical thrombectomy with arrow-trerotola device inpatients with
      thrombosed graft fistula].
AB  - PURPOSE: To assess the safety and efficacy of the Arrow-Trerotola percutaneous
      thrombectomy device in the treatment of thrombosed hemodialysis access grafts in
      dialysis patients. MATERIALS AND METHODS: Ten patients with graft fistula
      occlusion underwent mechanical thrombectomy with Arrow-Trerotola percutaneous
      thrombectomy device. Thirteen thrombectomy procedures were performed in ten
      patients. Technical success, complications, primary and secondary patency rates
      were noted. RESULTS: The technical success rate was 84% (11 of 13 procedures).
      There were no major complications. The mean follow-up period was 8.5 months. The
      graft fistula are still functional in seven patients. In 3 of 7 patients,
      additional procedures were needed for patency. The 3-month primary and secondary
      patency rates were 66% and 77% respectively. CONCLUSION: Percutaneous mechanical
      thrombectomy with the Arrow-Trerotola device is an effective method for the
      treatment of the thrombosed hemodialysis grafts.

PMID- 14661608
TI  - [Color Doppler US evaluation of hand circulation before radial artery harvest for
      coronary artery bypass grafting].
AB  - PURPOSE: The aim of this study was to evaluate color Doppler ultrasonography in
      assessing hand collateral circulation before radial artery harvesting for
      coronary artery bypass grafting. MATERIALS AND METHODS: The hand circulation of
      30 patients scheduled for coronary artery bypass grafting was assessed by means
      of the modified Allen test and Doppler ultrasonography dynamic test. The test was
      performed by recording the flow in the superficial palmar branch of the radial
      and ulnar arteries with and without compression of the radial artery. In the
      postoperative period hemodynamic changes in the ulnar artery were also detected
      by means of Doppler ultrasonography. RESULTS: Among the 30 patients, one had
      abnormal and the other 29 had normal Doppler ultrasonography dynamic test
      results. All the patients' modified Allen test results were also normal. In 14
      patients radial artery graft was used in the coronary artery bypass operation.
      CONCLUSION: Doppler ultrasonography dynamic test is an effective and noninvasive
      method in the preoperative evaluation of the hand collateral circulation for the
      safe removal of a radial artery graft.

PMID- 14661609
TI  - [Persistent fetal carotid-vertebrobasilar anastomoses].
AB  - The primitive trigeminal, otic (acoustic), hypoglossal, and proatiantal
      intersegmental arteries are persistent fetal anastomoses between the carotid and
      vertebrobasilar circulations. These fetal anastomoses regress at roughly the rate
      at which the posterior communicating and vertebral arteries develop. The purpose
      of this study is to review the persistent fetal carotid-vertebrobasilar
      anastomoses with MRI and DSA.

PMID- 14661610
TI  - [Case report: Ovarian torsion in inguinal canal].
AB  - Inguinal and scrotal hernias are two most common congenital anomalies observed by
      clinicians. The possibility of ovarian torsion following recurrent inguinal
      hernia is well known. Ultrasound examination of the inguinal region of a female
      infant showed a spherical, enlarged ovary with multiple tiny cysts. After the
      diagnosis of ovarian torsion, the patient underwent oopherectomy. It is possible
      to diagnose inguinal emergencies by high resolution ultrasonography.

PMID- 14661611
TI  - [Scurvy: radiologic findings].

PMID- 14661612
TI  - [Dysphagia caused by surrounding ascending diffuse idiopathic skeletal
      hyperostosis (Forestier disease)].

PMID- 14661613
TI  - [Infected urachal cyst].

PMID- 14661614
TI  - Life events in a prepubertal and early adolescent bipolar disorder phenotype
      compared to attention-deficit hyperactive and normal controls.
AB  - OBJECTIVE: To examine life events in subjects with a prepubertal and early
      adolescent bipolar disorder phenotype (PEA-BP) compared to those in subjects with
      attention-deficit hyperactivity disorder (ADHD) and normal controls (NC).
      METHODS: To optimize generalizeability, subjects with PEA-BP (n = 93) and ADHD (n
      = 81) were consecutively ascertained from pediatric and psychiatric sites.
      Subjects in the NC group (n = 94) were obtained from a random survey. PEA-BP was
      defined by Diagnostic and Statistical Manual of Mental Disorders (fourth edition)
      mania with at least one of the cardinal symptoms of mania (i.e., elation and/or
      grandiosity) to avoid diagnosing mania only by criteria that overlapped with
      those for ADHD. All subjects received comprehensive, blind research assessments
      of mothers about their children and separately of children about themselves.
      Assessment instruments included the Washington University in St. Louis Kiddie
      Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) and the Life
      Events Checklist. Data from the Life Events Checklist were examined by total life
      events and by subcategories of dependent, independent, or uncertain relationships
      to the child. RESULTS: Total, independent, dependent, and uncertain life events
      were all significantly more frequent in the PEA-BP subjects compared to both the
      ADHD and NC groups. CONCLUSIONS: Because there was no a priori reason to expect
      significantly more independent life events in the PEA-BP compared to the ADHD and
      NC groups, these results warrant further research into the role of life events in
      the onset of PEA-BP.

PMID- 14661615
TI  - [Respect and strengthen the prevention and treatment of infectious diseases in
      ophthalmology].

PMID- 14661616
TI  - [Evaluation on the measurement of intraocular pressure in the process of glaucoma
      diagnosis].

PMID- 14661617
TI  - [If is it necessary and practicable to screen glaucoma patients].

PMID- 14661618
TI  - [How to write a medical review paper].

PMID- 14661619
TI  - Orthograde retreatment and apexification after unsuccessful endodontic treatment,
      retreatment and apicectomy.
AB  - AIM: To describe a case where a second orthograde retreatment was successful in
      the management of an infected mandibular right first molar that previously had
      received both orthograde and retrograde treatments. SUMMARY: Periapical surgery
      is unlikely to be successful unless the root canal system has been adequately
      debrided and sealed. A case is described where orthograde endodontic treatment,
      retreatment and apicectomy were unsuccessful in the management of and infected
      mandibular right first molar. The periapical radiolucency eventually disappeared
      following a second orthograde retreatment. Teh second retreatment included 12
      months of intracanal calcium hydroxide placement to promote apexification, thus
      allowing subsequent controlled obturation with gutta percha and AH26. At a 5-year
      review following completion of treatment, the tooth remained asymptomatic and was
      in normal function. KEY LEARNING POINTS: Orthograde retreatment is a treatment
      option to manage refractory lesions in teeth that have previously received
      endodontic treatment, retreatment and apicectomy. Orthograde retreatment using
      long-term intracanal calcium hydroxide can help promote root-end closure of a
      resected apex.

PMID- 14661620
TI  - South Africa approves plan for universal access to antiretrovirals. Government
      also pledges to upgrade health system via recruitment and training of many health
      care workers.

PMID- 14661621
TI  - Leading the way in African home-based palliative care. Free oral morphine has
      allowed expansion of model home-based palliative care in Uganda.

PMID- 14661622
TI  - UN highlights North Korea in appeal for aid.

PMID- 14661623
TI  - European Parliament votes to fund stem-cell research.

PMID- 14661624
TI  - FDA chief attacks Canada's drug price controls.

PMID- 14661625
TI  - Reassessment of the unbound concentrations of unconjugated bilirubin in relation
      to neurotoxicity in vitro.

PMID- 14661626
TI  - Medicare overhaul wins Congressional support.

PMID- 14661627
TI  - Northern Uganda humanitarian crisis shocks UN chief. Rebels in northern districts
      have left people trapped in hunger, disease, poverty, and fear.

PMID- 14661628
TI  - Recommendation of occupational exposure limits (2003-2004).

PMID- 14661629
TI  - Nurses' work environment linked to medical errors.

PMID- 14661630
TI  - Sentinel node biopsy adopted as standard of care, despite lack of evidence.

PMID- 14661631
TI  - Exercise and healty weight in youth delay onset of breast cancer in women at
      highest risk.

PMID- 14661632
TI  - Interdisciplinary care and planning improves stroke outcomes.

PMID- 14661633
TI  - [Calcineurin and schizophrenia].

PMID- 14661634
TI  - [Semaphorins-integrins: an unexpected relationship].

PMID- 14661636
TI  - Medicare program; photocopying reimbursement methodology. Final rule.
AB  - This final rule increases the rate of reimbursement for expenses incurred by
      prospective payment system PPS) hospitals for photocopying medical records
      requested by Quality Improvement Organizations (QIOs), formerly known as
      Utilization and Quality Control Peer Review Organizations (PROs). We are
      increasing the rate from 7 cents per page to 12 cents per page to reflect
      inflationary changes in the labor and supply cost components of the formula. This
      final rule also provides for the periodic review and adjustment of the per-page
      reimbursement rate to account for inflation and changes in technology. The
      methodology for calculating the per-page reimbursement rate will remain
      unchanged. We are also providing for the payment of the expenses of furnishing
      photocopies to QIOs, to other providers subject to a PPS (for example, skilled
      nursing facilities and home health agencies), in accordance with the rules
      established for reimbursing PPS hospitals for these expenses.

PMID- 14661637
TI  - Medicare program; coverage and payment of ambulance services; inflation update
      for CY 2004. Final rule with comment period.
AB  - This final rule provides the sunset date for the interim bonus payment for rural
      ambulance mileage of 18 through 50 miles as required by the Medicare, Medicaid
      and State Child Health Insurance Program Benefits Improvement and Protection Act
      of 2000 (BIPA) and provides notice of the annual Ambulance Inflation Factor (AIF)
      for ambulance services for calendar year (CY) 2004. The statute requires that
      this inflation factor be applied in determining the fee schedule amounts and
      payment limits for ambulance services.

PMID- 14661638
TI  - Self-interest vs self-effacement.

PMID- 14661639
TI  - To approve or not approve?

PMID- 14661640
TI  - Yeast holds clue to link between aging and cancer.

PMID- 14661641
TI  - Studies reveal new HRT dangers.

PMID- 14661642
TI  - Folic acid in food prevents neuroblastoma.

PMID- 14661643
TI  - "Trojan horse" strategy enters phase 1 trial for breast cancer.

PMID- 14661644
TI  - Cancer risk increases for patients who undergo transplant.

PMID- 14661646
TI  - Current awareness in geriatric psychiatry.

PMID- 14661645
TI  - Subclinical metastases identified from stored biopsy samples.

PMID- 14661647
TI  - The opportunity for learning is a life-long experience--how mentoring can change
      your life.

PMID- 14661648
TI  - Human xenograft transplantation in animal research: risk assessment and hazard
      control for animal care workers.

PMID- 14661649
TI  - The Animal Care Council: a model for improved collaboration and communication.

PMID- 14661650
TI  - Revisiting the assessment of IACUC effectiveness in oversight of investigator
      compliance.

PMID- 14661651
TI  - ACLAM position statement on animal experimentation.

PMID- 14661652
TI  - Complementary health care practices: The Spiritual aspects of healing: an
      integral part of health and healing.

PMID- 14661653
TI  - Perioperative hypothermia in the high-risk surgical patient.
AB  - Perioperative hypothermia is common in high-risk surgical patients. Anaesthesia
      impairs central thermoregulation, allowing re-distribution of body heat. Cool
      ambient temperatures and high-volume fluid administration accelerate loss of heat
      to the environment. Randomized, controlled trials have proven that mild
      hypothermia increases the incidence of wound infection and prolongs
      hospitalization, increases the incidence of morbid cardiac events and ventricular
      tachycardia, and impairs coagulation. Other complications include enhanced
      anaesthetic drugs effects, prolonged recovery room stays, shivering, and impaired
      immune function. There is compelling animal evidence for cerebral protection by
      mild hypothermia. However, evidence for protection in surgical patients is not
      yet available. The most effective means of preventing perioperative hypothermia
      is active pre-warming. High ambient temperatures, warmed intravenous fluids and
      active cutaneous warming are useful intra-operatively, while active cutaneous
      warming and intravenous pethidine abolish post-operative shivering. Proper
      thermal management may reduce complications and improve the outcome in high-risk
      surgical patients.

PMID- 14661654
TI  - Fever during anaesthesia.
AB  - Fever occurs when pyrogenic stimulation activates thermal control centres. Fever
      is common during the perioperative period, but rare during anaesthesia. Although
      only a limited number of studies are available to explain how anaesthesia affects
      fever, general anaesthesia seems to inhibit fever by decreasing the
      thermoregulatory-response thresholds to cold. Opioids also inhibit fever;
      however, the effect is slightly less than that of general anaesthesia. In
      contrast, epidural anaesthesia does not affect fever. This suggests that
      hyperthermia, which is often associated with epidural infusions during labour or
      in the post-operative period, may be a true fever caused by inflammatory
      activation. Accordingly, this fever might be diminished in patients who receive
      opioids for pain treatment. Post-operative fever is a normal thermoregulatory
      response usually of non-infectious aetiology. Fever may be important in the host
      defence mechanisms and should not be routinely treated lest the associated risks
      exceed the benefits.

PMID- 14661655
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is an uncommon, life-threatening, acute
      pharmacogenetic disorder of the skeletal muscle cell. It manifests in susceptible
      individuals as a hypermetabolic response on exposure to halogenated volatile
      anaesthetics and depolarizing muscle relaxants. There may also be a relationship
      between susceptibility to MH, heat stroke and exercise-induced rhabdomyolysis.
      The pathophysiology of the crisis involves an uncontrolled release of cytoplasmic
      free calcium from the sarcoplasmic reticulum leading to activation of energy
      producing biochemical pathways. Organ system failure and rhabdomyolysis may occur
      as a result of high fever, hyperkalaemia and acidosis. The ryanodine receptor,
      the calcium-release channel of the sarcoplasmic reticulum, is the primary locus
      for malignant hypothermia susceptibility. Multiple mutations in the gene for the
      ryanodine receptor protein are causative. Other genes may also be involved. A
      classical fulminant crisis presents with a rising end-tidal carbon dioxide,
      skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Mortality may
      be as high as 70% if the syndrome is not recognized and treated. Immediate
      discontinuation of triggering agents, oxygenation, and correction of acidosis and
      electrolyte abnormalities, cooling and dantrolene are essential for treatment of
      the syndrome. Thanks to clinical and research investigations, widespread
      education and the introduction of dantrolene sodium, the mortality from MH is
      less than 5%. This chapter provides an overview and an update of MH.

PMID- 14661656
TI  - Consequences of inadvertent perioperative hypothermia.
AB  - Perioperative hypothermia triples the incidence of adverse myocardial outcomes in
      high-risk patients. Mild hypothermia significantly increases blood loss and
      augments allogeneic transfusion requirement, but the molecular pathophysiology of
      this effect remains to be elucidated. Only 1.9 degrees C core hypothermia triples
      the incidence of surgical wound infection following colon resection and increases
      the duration of hospitalization by 20%. Hypothermia adversely affects antibody-
      and cell-mediated immune defences, as well as the oxygen availability in the
      peripheral wound tissues. Mild perioperative hypothermia changes the kinetics and
      action of various anaesthetic and paralysing agents, increases thermal
      discomfort, and is associated with delayed post-anaesthetic recovery. Finally,
      mild core hypothermia influences pulse oximetry monitoring and various
      electrophysiological indices of the nervous system, with questionable clinical
      significance, as yet.

PMID- 14661657
TI  - Therapeutic hypothermia.
AB  - Hypothermia is common during anaesthesia and surgery owing to anaesthetic-induced
      inhibition of thermoregulatory control. Perioperative hypothermia is associated
      with numerous complications. However, for certain patient populations, and under
      specific clinical conditions, hypothermia can provide substantial benefits.
      Lowering core temperature to 32-34 degrees C may reduce cell injury by
      suppressing excitotoxins and oxygen radicals, stabilizing cell membranes, and
      reducing the number of abnormal electrical depolarizations. Evidence from animal
      studies indicates that even mild hypothermia provides substantial protection
      against cerebral ischaemia and myocardial infarction. Mild hypothermia has been
      shown to improve outcome after cardiac arrest in humans. Randomized trials are in
      progress to evaluate the potential benefits of mild hypothermia during aneurysm
      clipping and after stroke or acute myocardial infraction. However, as hypothermia
      can cause unwanted side-effects, further research is needed to better quantify
      the risks and benefits of therapeutic hypothermia.

PMID- 14661658
TI  - Monitoring and thermal management.
AB  - Anaesthesia alters normal thermoregulatory control of the body, usually leading
      to perioperative hypothermia. Hypothermia is associated with a large number of
      serious complications. To assess perianaesthetic hypothermia, core temperature
      should be monitored vigorously. Pulmonary artery, tympanic membrane, distal
      oesophageal or nasopharyngeal temperatures reflect core temperature reliably.
      Core temperatures can be often estimated with reasonable accuracy using oral,
      axillary and bladder temperatures, except during extreme thermal perturbations.
      The body site for measurements should be chosen according to the surgical
      procedure. Unless hypothermia is specifically indicated, efforts should be made
      to maintain intraoperative core temperatures above 36 degrees C. Forced air is
      the most effective, commonly available, non-invasive warming method. Resistive
      heating electrical blankets and circulating water garment systems are an equally
      effective alternative. Intravenous fluid warming is also helpful when large
      volumes are required. In some patients, induction of mild therapeutic hypothermia
      may become an issue for the future. Recent studies indicate that patients
      suffering from neurological disease may profit from rapid core cooling.

PMID- 14661659
TI  - Impact of multislice CT on imaging of acute abdominal disease.
AB  - The increased speed, greater coverage, and thinner slices of MSCT are exciting
      developments in radiology, and these feature should only improve with newer
      generation multislice scanners. The impact of this technology on abdominal
      imaging has just begun.

PMID- 14661660
TI  - Radiologic diagnosis of gastrointestinal perforation.
AB  - Perforations of the gastrointestinal tract have many causes. Holes in the wall of
      gastrointestinal organs can be created by blunt or penetrating trauma, iatrogenic
      injury, inflammatory conditions that penetrate the serosa or adventitia,
      extrinsic neoplasms that invade the gastrointestinal tract, or primary neoplasms
      that penetrate outside the wall of gastrointestinal organs. This article provides
      a radiologic approach for investigating the wide variety of gastrointestinal
      perforations. General principles about contrast agents and studies are reviewed,
      and then perforations in specific gastrointestinal organs are discussed.

PMID- 14661661
TI  - The acute right lower quadrant: CT evaluation.
AB  - Acute right lower quadrant pain is a nonspecific but common clinical complaint.
      Appendicitis is the most common cause of acute right lower quadrant pain and CT
      has become the most reliable imaging method in the evaluation of these patients.
      Although there is controversy regarding the best way to perform CT in this
      setting, oral and i.v. contrast-enhanced CT remains the most commonly used
      technique. CT with oral and i.v. contrast material facilitates diagnosis of
      appendicitis and the numerous other entities that may cause right lower quadrant
      pain.

PMID- 14661662
TI  - Adult intussusception: diagnosis and clinical relevance.
AB  - Intussusception is relatively rare in the adult population and differs
      substantially from pediatric intussusception. Most adult intussusceptions
      identified at surgery are caused by a definable structural lesion, a substantial
      proportion of which are malignant, particularly in the colon. Small bowel
      intussusceptions, however, have a lower prevalence of malignancy. Diagnosis of
      adult intussusception can be made reliably with noninvasive imaging techniques.
      CT is now widely regarded as the modality of choice for diagnosing
      intussusception in adults, but ultrasound and MR imaging have also been used
      effectively. Determination of the presence of a malignant lead point remains
      problematic because an edematous or hemorrhagic intussuscipiens may mimic a mass
      on each modality. Markers for bowel viability have been described but are not
      precise. Treatment of the persistent symptomatic intussusception in which
      neoplasia is suspected is surgical, and preoperative reduction is
      contraindicated. Transient relatively asymptomatic enteric intussusceptions
      discovered by imaging may not require intervention.

PMID- 14661663
TI  - CT of acute abdominal aortic disorders.
AB  - Aortic aneurysm rupture, aortic dissection, PAU, acute aortic occlusion,
      traumatic aortic injury, and aortic fistula represent acute abdominal aortic
      conditions. Because of its speed and proximity to the emergency department,
      helical CT is the imaging test of choice for these conditions. MR imaging also
      plays an important role in the imaging of aortic dissection and PAU, particularly
      when the patient is unable to receive intravenous contrast material. In this era
      of MDCT, conventional angiography is used as a secondary diagnostic tool to
      clarify equivocal findings on cross-sectional imaging. Ultrasound is helpful when
      CT is not readily available and the patient is unable or too unstable to undergo
      MR imaging.

PMID- 14661664
TI  - Blunt injury to mesentery and small bowel: CT evaluation.
AB  - Helical CT now allows rapid acquisition of sections through the abdomen and
      pelvis with optimal vascular opacification and minimal motion artifact. Oral
      contrast may aid in the identification of subtle bowel and mesenteric injuries
      and does not have any significant deleterious effects. CT findings of
      extraluminal enteric contrast, active hemorrhage, or free intraperitoneal
      retroperitoneal air allow accurate diagnosis of SBMI in the setting of blunt
      abdominal trauma. Mesenteric hematoma in association with bowel wall thickening
      or the presence of significant amounts of free fluid without solid organ injury
      is highly suspicious for SBMI requiring laparotomy. CT alone or in concert with
      DPL and physical examination is a valuable tool in the timely diagnosis and
      treatment of bowel and mesenteric injury caused by blunt trauma.

PMID- 14661665
TI  - Spontaneous intraperitoneal hemorrhage: imaging features.
AB  - Spontaneous intraperitoneal bleeding can result from a vast array of etiologies.
      Fortunately, most are uncommon and currently available imaging modalities can be
      used to differentiate them in almost all cases. Meticulous imaging technique and
      careful observation of key imaging features are important for accurate
      characterization of the organ of origin of the spontaneous bleeding. CT is the
      single most important imaging technique in the detection and characterization of
      spontaneous intraperitoneal bleeding. Further development in multidetector
      technology, such as the introduction of new machines with 8 or 16 detectors,
      should improve the effectiveness of CT further. Sonography and MR imaging are
      complimentary to CT, especially in patients with pelvic abnormalities or
      equivocal CT findings.

PMID- 14661666
TI  - Ultrasound and CT evaluation of emergent gallbladder pathology.
AB  - Ultrasound is the initial imaging modality of choice for the evaluation of
      suspected acute gallbladder disorders, and is often sufficient for correct
      diagnosis. CT also plays a vital role, however, in the evaluation of acute
      gallbladder pathology. CT is particularly useful in situations where ultrasound
      findings are equivocal. CT is also extremely valuable in the assessment of
      suspected complications of acute cholecystitis, particularly emphysematous
      cholecystitis, hemorrhagic cholecystitis, and gallbladder perforation, which are
      often very difficult diagnoses to establish at sonography. If CT is the initial
      imaging test performed in a patient with abdominal pain of uncertain etiology,
      recognition of the various disorders described in this article may eliminate the
      need for further imaging and facilitate appropriate management.

PMID- 14661667
TI  - Interventional approach to pancreatic fluid collections.
AB  - Interventional radiologic catheter drainage may be an effective therapeutic
      approach to fluid collections complicating acute pancreatitis. Pancreatic
      pseudocysts and abscess are the most common conditions requiring radiologic
      intervention. Imaging guidance is best performed under CT control allowing
      precise definition of access route, catheter placement, and response. Access
      routes are chosen to avoid traversing vital intervening structures, especially
      the pleural space, colon, and small bowel. Optimal results are achieved with the
      use of large-bore multihole catheters, prolonged duration of drainage, and
      careful collaboration with the surgical team.

PMID- 14661668
TI  - Ultrasonography of the acute abdomen: gastrointestinal conditions.
AB  - Although multislice, helical CT is increasingly replacing ultrasonography for the
      evaluation of patients with acute abdominal pain, ultrasound does have certain
      specific advantages over CT. This article discusses the advantages of ultrasound
      in imaging of the acute abdomen, exploring such areas as appendicitis, ileocecal
      Crohn's disease, infectious ileocolitis and infectious ileocecitis, mesenteric
      lymphadenitis, cecal carcinoma, sigmoid diverticulitis, right-sided colonic
      diverticulitis, and perforated peptic ulcer.

PMID- 14661669
TI  - MR imaging in abdominal emergencies.
AB  - The use of MR imaging in the emergency setting is evolving. Clear indications
      include situations in need of contrast media when iodinated contrast cannot be
      administered or to facilitate assessments in pregnant patients and children when
      exposure to ionizing radiation is considered unacceptable. The availability of
      rapid, motion-immune sequences now makes MR imaging a feasible study in less
      cooperative patients extending the range of patients for whom a diagnostic study
      can be achieved. Capitalizing on the unique benefits of MR imaging there is
      optimism that MR imaging can eliminate test redundancy and impact patient care in
      a cost-effective manner. Further investigations are needed to identify the
      diagnostic algorithms for which this favorable use holds true.

PMID- 14661670
TI  - Selective role of nuclear medicine in evaluating the acute abdomen.
AB  - The imaging evaluation of the acute abdomen has clearly evolved with the
      introduction of high-resolution imaging techniques, such as CT, US, and MR
      imaging, leaving scintigraphic examinations an important, though selective, role
      based on their noninvasive, physiologic, and functional nature. Proper use of
      these examinations among all the diagnostic methods requires a good understanding
      of their strengths and limitations.

PMID- 14661671
TI  - Complications of liver transplantation: imaging and intervention.
AB  - The radiologist can play a key role in diagnosis and management of many of the
      infectious, inflammatory, and neoplastic processes that affect patients after
      liver transplantation. Familiarity and skill with the full range of diagnostic
      and interventional tools are essential for radiologists dealing with transplant
      patients, even outside the medical centers where the transplantation takes place.

PMID- 14661672
TI  - Stamp vignette on medical science. Rita Levi-Montalcini--Nobel Prize for work in
      neurology.

PMID- 14661673
TI  - Vitamin D deficiency: what a pain it is.

PMID- 14661674
TI  - How sweet is euglycemia in critically ill patients?

PMID- 14661675
TI  - Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific
      musculoskeletal pain.
AB  - OBJECTIVE: To determine the prevalence of hypovitaminosis D in primary care
      outpatients with persistent, nonspecific musculoskeletal pain syndromes
      refractory to standard therapies. PATIENTS AND METHODS: In this cross-sectional
      study, 150 patients presented consecutively between February 2000 and June 2002
      with persistent, nonspecific musculoskeletal pain to the Community University
      Health Care Center, a university-affiliated inner city primary care clinic in
      Minneapolis, Minn (45 degrees north). Immigrant (n = 83) and nonimmigrant (n =
      67) persons of both sexes, aged 10 to 65 years, from 6 broad ethnic groups were
      screened for vitamin D status. Serum 25-hydroxyvitamin D levels were determined
      by radioimmunoassay. RESULTS: Of the African American, East African, Hispanic,
      and American Indian patients, 100% had deficient levels of vitamin D (< or = 20
      ng/mL). Of all patients, 93% (140/ 150) had deficient levels of vitamin D (mean,
      12.08 ng/mL; 95% confidence interval, 11.18-12.99 ng/mL). Nonimmigrants had
      vitamin D levels as deficient as immigrants (P = .48). Levels of vitamin D in men
      were as deficient as in women (P = .42). Of all patients, 28% (42/150) had
      severely deficient vitamin D levels (< or = 8 ng/mL), including 55% of whom were
      younger than 30 years. Five patients, 4 of whom were aged 35 years or younger,
      had vitamin D serum levels below the level of detection. The severity of
      deficiency was disproportionate by age for young women (P < .001), by sex for
      East African patients (P < .001), and by race for African American patients (P =
      .006). Season was not a significant factor in determining vitamin D serum levels
      (P = .06). CONCLUSION: All patients with persistent, nonspecific musculoskeletal
      pain are at high risk for the consequences of unrecognized and untreated severe
      hypovitaminosis D. This risk extends to those considered at low risk for vitamin
      D deficiency: nonelderly, nonhousebound, or nonimmigrant persons of either sex.
      Nonimmigrant women of childbearing age with such pain appear to be at greatest
      risk for misdiagnosis or delayed diagnosis. Because osteomalacia is a known cause
      of persistent, nonspecific musculoskeletal pain, screening all outpatients with
      such pain for hypovitaminosis D should be standard practice in clinical care.

PMID- 14661676
TI  - Association between hyperglycemia and increased hospital mortality in a
      heterogeneous population of critically ill patients.
AB  - OBJECTIVE: To investigate the relationship between hyperglycemia and hospital
      mortality in a heterogeneous group of critically ill patients. PATIENTS AND
      METHODS: Retrospective data were reviewed for 1826 consecutive patients whose
      glucose values were obtained during their intensive care unit stay at The
      Stamford Hospital in Stamford, Conn, between October 1, 1999, and April 4, 2002.
      RESULTS: Mean and maximum glucose values were significantly higher among
      nonsurvivors than among survivors for the entire group (P < .001) and for each
      subgroup except for patients with septic shock. The lowest hospital mortality,
      9.6%, occurred among patients with mean glucose values between 80 and 99 mg/dL.
      Hospital mortality increased progressively as glucose values increased, reaching
      42.5% among patients with mean glucose values exceeding 300 mg/dL. Within each of
      3 groupings of Acute Physiology and Chronic Health Evaluation II (APACHE II)
      scores (0-14; 15-24; > or = 25), mean and maximum glucose values were higher
      among nonsurvivors than among survivors. CONCLUSION: Even a modest degree of
      hyperglycemia occurring after intensive care unit admission was associated with a
      substantial increase in hospital mortality in patients with a wide range of
      medical and surgical diagnoses. Analysis of glucose values added predictive power
      above that achieved by APACHE II scores alone. These results have important
      implications for the glycemic management of critically ill patients.

PMID- 14661677
TI  - Ethnic differences in cardiac potassium channel variants: implications for
      genetic susceptibility to sudden cardiac death and genetic testing for congenital
      long QT syndrome.
AB  - OBJECTIVE: To determine the spectrum, frequency, and ethnic-specificity of
      channel variants in the potassium channel genes implicated in congenital long QT
      syndrome (LQTS) among healthy subjects. SUBJECTS AND METHODS: Genomic DNA from
      744 apparently healthy individuals-305 black, 187 white, 134 Asian, and 118
      Hispanic--was subject to a comprehensive mutational analysis of the 4 LQTS
      causing potassium channel genes: KCNQ1 (LQT1), KCNH2 (LQT2), KCNE1 (LQT5), and
      KCNE2 (LQT6). RESULTS: Overall, 49 distinct amino acid-altering variants (36
      novel) were identified: KCNQ1 (n = 16), KCNH2 (n = 25),KCNE1 (n = 5), and KCNE2
      (n = 3). More than half of these variants (26/49) were found exclusively in black
      subjects. The known K897T-HERG and the G38S-min K common polymorphisms were
      identified in all 4 ethnic groups. Excluding these 2 common polymorphisms, 25% of
      black subjects had at least 1 nonsynonymous potassium channel variant compared
      with 14% of white subjects (P < .01). CONCLUSIONS: To our knowledge, this study
      represents the first comprehensive determination of the frequency and spectrum of
      cardiac channel variants found among healthy subjects from 4 major ethnic groups.
      Defining the population burden of genetic variants in these critical cardiac ion
      channels is crucial for proper interpretation of genetic test results of
      individuals at risk for LQTS. This compendium provides a resource for
      epidemiological and functional investigation of variant effects on the
      repolarization properties of cardiac tissues, including susceptibility to lethal
      cardiac arrhythmias.

PMID- 14661678
TI  - Intracranial aneurysms in patients with coarctation of the aorta: a prospective
      magnetic resonance angiographic study of 100 patients.
AB  - OBJECTIVE: To determine the frequency of intracranial aneurysms (IAs) detected in
      patients with coarctation of the aorta (CoA) with use of magnetic resonance
      angiography. PATIENTS AND METHODS: From January 1, 1980, to September 30, 2002,
      277 adult patients with CoA were seen at the Mayo Clinic in Rochester, Minn, and
      were invited to participate in a study to detect IAs. Of these 277 patients (mean
      +/- SD age, 41.6 +/- 16.5; 70 men), 100 underwent cranial magnetic resonance
      angiography. RESULTS: Ten patients had an IA (95% confidence interval, 5%-18%),
      with a mean diameter of 3.5 mm (range, 2.0-8.0 mm). The frequency of IA was
      significantly higher than that predicted in the general population (10% vs 2%; P
      < .001). One patient had surgical intervention. No clinical or geographical
      differences were found between patients with CoA and IA and patients with CoA and
      no IA. CONCLUSIONS: The frequency of IA among patients with CoA is approximately
      5-fold that of the general population. Although no risk factors were identified
      in this cohort, additional prospective evaluation is warranted. These data
      suggest that noninvasive cerebral imaging to screen for IA should be considered
      in patients with CoA.

PMID- 14661679
TI  - Laparoscopic adrenalectomy for pheochromocytoma.
AB  - OBJECTIVE: To determine the safety and results of laparoscopic resection of
      benign pheochromocytomas. PATIENTS AND METHODS: We retrospectively reviewed the
      medical charts of all patients who underwent laparoscopic adrenalectomy for
      benign pheochromocytomas at all 3 Mayo Clinic sites between January 1, 1992, and
      December 31, 2001. Demographics, comorbidities, clinical presentation, imaging
      studies, biochemical findings, operative intervention, and outcome were examined.
      Long-term follow-up was obtained via chart review and/or by direct telephone
      contact with the patient or a relative. RESULTS: Twenty-four women and 23 men
      with a mean age of 53.1 years (range, 16-81 years) underwent attempted
      laparoscopic resection of pheochromocytomas. In 5 patients, the procedure was
      converted to open laparotomy because of bleeding (2), inadequate exposure (2),
      and adhesions (1). The mean tumor size was 4.3 cm. The mean operative time (181.8
      vs 1405 minutes; P = .03), mean hospital stay (6.00 vs 2.64 days; P < .001), and
      mean blood loss (340 mL vs 80 mL; P < .001) were greater in patients who
      underwent open laparotomy vs those who underwent laparoscopic resection. All
      specimens were classified as benign. The mean follow-up was 41 months (range, 10
      89 months). No patients experienced a recurrence or developed metastatic disease.
      CONCLUSIONS: In light of surgical and anesthesia expertise, laparoscopic
      resection of benign pheochromocytomas is safe and effective with resultant short
      hospital stays. A low threshold to convert to an open procedure reduces operative
      times and decreases potentially serious complications. Although there have been
      no recurrences to date, long-term follow-up is required for all patients,
      especially those with hereditary forms of pheochromocytomas.

PMID- 14661680
TI  - Risk stratification and interventional cardiology: Robert L. Frye Lecture.
AB  - Risk stratification and risk-benefit ratios are extremely important in guiding
      patient-physician interactions as well as patient and family counseling. Risks
      associated with percutaneous transluminal coronary angioplasty are (1) compromise
      of the vessel lumen or vessel integrity, (2) unsuccessful procedure, and (3)
      restenosis. Predicting mortality risk depends on the specific patient population
      to be treated and on the specific mortality model used. The most common models
      are those from New York State, the American College of Cardiology, the Northern
      New England Cooperative Group, the University of Michigan, and The Cleveland
      Clinic Foundation. As more data and sophisticated analyses become available, risk
      stratification will become more accurate as long as the approach used is
      straightforward, makes intuitive sense, and is easy and efficient to apply.

PMID- 14661681
TI  - Controversies regarding the effects of growth hormone on the heart.
AB  - Growth hormone (GH) profoundly affects the developing and adult myocardium. Adult
      patients with GH deficiency (GHD) and GH excess (acromegaly) provide important
      models in which to understand the effects of GH in adult cardiac physiology. An
      increasing body of clinical and experimental evidence illustrates the specific
      physiological abnormalities that are likely associated with the excess
      cardiovascular mortality observed in both acromegaly and GHD. Because human GH
      replacement is now available to treat adults with GHD, new questions emerge about
      the long-term cardiovascular effects of replacement therapy. In multiple trials,
      GH therapy for congestive heart failure has been proved ineffective in the
      absence of preexisting GHD. Case reports suggest that, in the setting of GHD, GH
      therapy can exert a potent beneficial effect on congestive heart failure. Long
      term studies addressing cardiovascular morbidity and mortality are needed to
      assess the role of GH therapy for GHD.

PMID- 14661682
TI  - Treatment of brain metastases from melanoma.
AB  - Brain metastases from malignant melanoma have a poor prognosis, and treatment can
      be difficult because of rapid progression of the disease. To help define the
      treatment of this disease, we reviewed the published literature on brain
      metastases from melanoma. If a solitary metastasis is present, surgery might be
      beneficial, especially if systemic disease is absent. Stereotactic radiosurgery
      is a less invasive, attractive option for solitary or oligometastatic (up to 6)
      lesions. External beam whole-brain radiation therapy can produce responses and
      frequently palliates symptoms, but as the sole therapy, it is unlikely to
      eradicate brain metastases. Chemotherapy may be gaining a role with newer agents
      that penetrate the blood-brain barrier. Combined modality therapy appears to be
      the future direction of treatment of multiple metastases.

PMID- 14661683
TI  - Group and individual treatment strategies for distress in cancer patients.
AB  - Many cancer patients experience distress during the course of their illness.
      Recently, the National Comprehensive Cancer Network recommended that all cancer
      patients receive evaluation and treatment of distress as a routine part of their
      care. For some patients, psychosocial interventions may be helpful, but which
      patients benefit from what type of psychosocial interventions is unclear. To
      highlight the importance of this problem, this article examines the prevalence of
      distress in cancer patients and reviews the evidence that supports that cancer
      patients benefit from group and individual treatment strategies. Several
      randomized studies have examined the effects of group or individual therapy on
      both the emotional and the physiological well-being of cancer patients. Both
      individual and group interventions that are structured have proved effective in
      reducing distress. Clearly, more investigation is warranted and future research
      is needed to advance the understanding of structured interventions, to examine
      support groups, and to tailor psychological interventions to meet individual
      needs of distressed cancer patients.

PMID- 14661684
TI  - Obstructive sleep apnea-hypopnea syndrome.
AB  - Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repetitive
      episodes of airflow reduction (hypopnea) or cessation (apnea) due to upper airway
      collapse during sleep. Increasing recognition and a greater understanding of the
      scope of this condition have substantially affected the practices of many
      clinicians. This review provides practical information for physicians assessing
      patients with OSAHS. It discusses complications, clinical recognition, the
      polysomnographic report, and treatment of OSAHS, including strategies for
      troubleshooting problems associated with continuous positive airway pressure
      therapy.

PMID- 14661685
TI  - Sudden progression of lumbar disk protrusion during vertebral axial decompression
      traction therapy.
AB  - Vertebral axial decompression (VAX-D) is a form of spinal traction that is widely
      promoted as an effective and safe treatment of degenerated and herniated lumbar
      intervertebral disks. Information targeted at the general public emphasizes that
      the treatment is completely risk-free. We describe a patient with a large lumbar
      disk protrusion who experienced sudden, severe exacerbation of radicular pain
      during a VAX-D therapy session. Follow-up magnetic resonance imaging of the
      lumbar region showed marked enlargement of the disk protrusion, and urgent
      microdiskectomy was required. To our knowledge, this is the first reported
      complication of VAX-D therapy. This case shows that VAX-D therapy has the
      potential to cause sudden deterioration requiring urgent surgical intervention.

PMID- 14661686
TI  - Acute myocardial infarction in a professional diver after jellyfish sting.
AB  - To our knowledge, acute myocardial infarction after jellyfish envenomation has
      not been reported previously. We describe a previously healthy 45-year-old male
      diver who had an acute inferior myocardial infarction with right ventricular
      involvement after a jellyfish sting on his left forearm while diving in the Gulf
      Sea. The patient had a normal controlled ascent after the incident. He had no
      risk factors for coronary artery disease, and cardiac catheterization revealed
      normal coronary arteries. Acute myocardial infarction should be considered in
      patients who experience chest pain or have hemodynamic compromise after jellyfish
      envenomation.

PMID- 14661687
TI  - Isolated intraparotid Kaposi sarcoma in human immunodeficiency virus type 1
      infection.
AB  - Isolated Kaposi sarcoma (KS) of the parotid gland is an uncommon but distinct
      entity in patients with human immunodeficiency virus type 1 (HIV-1). A 30-year
      old white homosexual man in whom HIV-1 had been diagnosed 2 years previously
      developed right parotid gland enlargement in the absence of constitutional
      symptoms. He had been taking zidovudine, lamivudine, and indinavir; his CD4 cell
      count was 0.297 x 10(9)/L, and HIV-1 RNA load was 47 copies/mL. After surgical
      excision of the parotid gland, biopsy findings disclosed KS of an intraparotid
      lymph node. A literature review revealed 6 other men with HIV-1 and isolated
      parotid KS. To our knowledge, our patient is the first to have received triple
      antiretroviral therapy with excellent immunological and virological response and
      parotid gland enlargement that might reflect immune reconstitution. Even in the
      absence of skin or other lesions, KS should be considered in the differential
      diagnosis of parotid gland enlargement in patients with HIV-1, even in those who
      are responding to highly active antiretroviral treatment.

PMID- 14661688
TI  - Principles of drug therapy for the elderly patient.
AB  - Physicians will treat larger numbers of elderly patients as the US population
      ages. Being treated simultaneously for more than 1 condition with multiple
      prescription drugs is only 1 reason why elderly patients are at greater risk of
      experiencing adverse drug reactions. The need for physicians to minimize the
      incidence of these reactions has become incumbent on both physicians and
      administrators. We review the underlying reasons why the elderly population is at
      risk of adverse drug reactions and summarize the principles of drug-drug
      interaction, metabolism, and distribution, which can help elderly patients
      receive proper pharmacological treatment.

PMID- 14661689
TI  - Imatinib mesylate-induced interstitial pneumonitis.

PMID- 14661690
TI  - West Nile virus and insecticide resistance.

PMID- 14661691
TI  - On prosthodontic research: old baggage, new directions.

PMID- 14661692
TI  - On prosthodontic education: current dilemmas.

PMID- 14661693
TI  - On prosthodontic community responsibility.

PMID- 14661694
TI  - On biological and social interfaces in prosthodontics: format for reviews.

PMID- 14661695
TI  - Regional, generational, educational, personal, and other factors that influence a
      provider's choice of treatment: I.

PMID- 14661696
TI  - Regional, generational, educational, personal, and other factors that influence a
      provider's choice of treatment: II.

PMID- 14661697
TI  - Demographic, psychological, sociological, and economic variables and other
      factors that justify the need for prosthodontic services, and that help to assess
      the outcome of care.

PMID- 14661698
TI  - Relative cost-effectiveness of various prosthodontic treatments.

PMID- 14661699
TI  - Demographic, psychological, sociological, and economic variables and other
      factors that influence a patient's choice of prosthodontic treatment.

PMID- 14661700
TI  - Titanium: the ultimate solution or an evolutionary step?

PMID- 14661701
TI  - The host-implant interface: biology.

PMID- 14661702
TI  - Biomechanical aspects of oral/maxillofacial implants.

PMID- 14661703
TI  - Is the tissue-integrated interface a periodontium analogue: myth or metaphor?

PMID- 14661704
TI  - Patient-mediated concerns: is there a limit to the prescription of implant
      therapy?

PMID- 14661705
TI  - Clinical benefits of dental implant treatment.

PMID- 14661706
TI  - Patient-mediated concerns.

PMID- 14661707
TI  - Dentist-mediated concerns.

PMID- 14661708
TI  - Bone quantity and quality: are they relevant predictors of implant outcomes?

PMID- 14661709
TI  - Implant design and surface factors.

PMID- 14661710
TI  - Biological compatibility of prosthodontic materials.

PMID- 14661711
TI  - Effect of prosthetic remedial treatments on the oral health status of individuals
      and populations.

PMID- 14661712
TI  - Evidence for changes in removable partial and complete denture treatment and
      biologic compatibility.

PMID- 14661713
TI  - Resin-bonded fixed partial dentures as alternatives to conventional fixed
      treatment.

PMID- 14661714
TI  - Loss of serviceability of remedial prosthodontic treatment for partially and
      totally edentulous patients.

PMID- 14661716
TI  - Longevity expectations of prosthodontic treatments for dentate and edentulous
      patients.

PMID- 14661715
TI  - Why do prosthodontic treatments lose serviceability?

PMID- 14661717
TI  - Biological adaptation and normative values.

PMID- 14661718
TI  - Satisfactory occlusal relations for the individual with a craniofacial anomaly.

PMID- 14661719
TI  - The rationale for management of morphologic variations and nonphysiologic
      occlusion in the young dentition.

PMID- 14661720
TI  - Determinants of a healthy aging dentition: maximum number of bilateral centric
      stops and optimum vertical dimension of occlusion.

PMID- 14661721
TI  - Determinants of a healthy aging dentition: freedom in the retrusive range of
      occlusal contacts and multidimensional freedom for functional tooth contact.

PMID- 14661722
TI  - Usual and unusual orofacial motor activities associated with tooth wear.

PMID- 14661723
TI  - Local factors associated with parafunction and prosthodontics.

PMID- 14661724
TI  - Musculoskeletal disorders and the occlusal interface: I.

PMID- 14661725
TI  - Musculoskeletal disorders and the occlusal interface: II.

PMID- 14661726
TI  - Erosion and tooth surface loss.

PMID- 14661727
TI  - Changes of compressibility of low density lipoproteins following copper mediated
      oxidation.
AB  - The methods of measuring the ultrasound velocity and density were used for study
      the adiabatic compressibility of low density lipoproteins (LDL) during their
      oxidation. We showed, that copper-mediated oxidation of LDL resulted in a
      decrease of apparent specific compressibility, phi(k)/beta0, of lipoproteins. The
      changes of ultrasound velocity and phi(k)/beta0 value started much earlier than
      the beginning of propagation phase corresponding to the fast increase in
      concentration of conjugated dienes, measured by absorption at 230 nm. It was
      assumed that the changes of compressibility could be in particularly due to
      increase in ordering of the phospholipids during reductive activation of Cu2+.

PMID- 14661728
TI  - The effects of H2O2 on electromechanical activity of the ileum longitudinal
      muscle.
AB  - The effects of H2O2 on electrical and mechanical activity of the longitudinal
      layer from the guinea-pig ileum were studied using sucrose-gap technique and the
      influence of H2O2 on ionic current was investigated in single smooth muscle cells
      by the patch-clamp method. In most of the preparations tested, the spontaneous
      activity observed was composed of slow waves with superimposed action potentials
      (APs). Both were resistant to tetrodotoxin and atropine. H2O2 (1 mmol/l) evoked
      sustained 3-5 mV membrane depolarisation, doubled the amplitude of the slow waves
      and increased their frequency, augmented the APs and reduced their splitting.
      These changes were accompanied with significant contraction, which had an
      amplitude comparable to that of the tonic component of 50 mmol/l K+-induced
      contraction. Calcium-free solution caused membrane depolarisation, reduction of
      the slow wave amplitude and frequency, disappearance of APs and decreased the
      mechanical tension of the preparations. Application of H2O2 (1 mmol/l) into the
      zero-calcium bath solution recovered the APs, which was accompanied by a low
      amplitude contraction. H2O2 (up to 1 mmol/l) increased the L-type calcium current
      (I(Ca)) both under conventional whole-cell patch-clamp configuration and under
      amphotericin-perforated patches by 16 +/- 3%. These data demonstrated that
      contractile response of the ileum longitudinal smooth muscle preparation evoked
      by H2O2 was mainly due to the enhanced electrical activity.

PMID- 14661729
TI  - Hydroxylation of phenol to catechol by Candida tropicalis: involvement of
      cytochrome P450.
AB  - Microsomal preparations isolated from yeast Candida tropicalis (C. tropicalis)
      grown on three different media with or without phenol were isolated and
      characterized for the content of cytochrome P450 (CYP) (EC 1.14.15.1). While no
      CYP was detected in microsomes of C. tropicalis grown on glucose as the carbon
      source, evidence was obtained for the presence of the enzyme in the microsomes of
      C. tropicalis grown on media containing phenol. Furthermore, the activity of
      NADPH: CYP reductase, another enzyme of the microsomal CYP-dependent system, was
      markedly higher in cells grown on phenol. Microsomes of these cells oxidized
      phenol. The major metabolite formed from phenol by microsomes of C. tropicalis
      was characterized by UV/vis absorbance and mass spectroscopy as well as by the
      chromatographic properties on HPLC. The characteristics are identical to those of
      catechol. The formation of catechol was inhibited by CO, the inhibitor of CYP,
      and correlated with the content of cytochrome P450 in microsomes. These results,
      the first report showing the ring hydroxylation of phenol to catechol with the
      microsomal enzyme system of C. tropicalis, strongly suggest that CYP-catalyzed
      reactions are responsible for this hydroxylation. The data demonstrate the
      progress in resolving the enzymes responsible for the first step of phenol
      degradation by the C. tropicalis strain.

PMID- 14661730
TI  - Expression of the rat liver haptoglobin gene is mediated by isoforms of
      C/EBPalpha, -beta and -delta proteins.
AB  - CCAAT/enhancer binding proteins (C/EBP) alpha, -beta and -delta play an important
      role in mediating I interleukin-6 (IL-6) dependent expression of acute-phase
      protein (APP) genes in liver during acute-phase (AP) response. Based on the
      presence of type IL-6 responsive element (IL-6 RE) in the rat haptoglobin (Hp)
      gene promoter we assumed that some C/EBPalpha, -beta and/or -delta isoforms could
      mediate the expression of this gene during turpentine-induced AP response. By
      Western immunoblot and Northern blot assays, we found that turpentine treatment
      of rats led to a coordinate induction of C/EBPbeta and -delta as well as
      repression of C/EBPalpha isoforms pool levels in rat liver nuclear extracts (NEs)
      which was preceded by an adequate alteration of their mRNAs expression in liver.
      Consequently, results of DNA affinity chromatography revealed that affinity of
      certain C/EBPalpha isoforms to bind the type I IL-6 RE within the rat Hp gene
      promoter decreased whereas affinities of certain C/EBPbeta isoforms and
      C/EBPdelta were increased and induced, respectively. Our data suggest that
      turpentine-induced alterations of C/EBPalpha, -beta and -delta pool levels and
      DNA-binding activities can be regarded as an integral part of activation of the
      Hp gene expression in the course of AP response.

PMID- 14661731
TI  - Monitoring of premitotic and postmitotic apoptosis in gamma-irradiated HL-60
      cells by the mitochondrial membrane protein-specific monoclonal antibody APO2.7.
AB  - BACKGROUND: Majority of hematopoietic cells die by apoptosis after irradiation
      with ionizing radiation. In present study it is shown that human promyelocytic
      leukemia HL-60 cells can undergo two different types of apoptosis, premitotic and
      postmitotic. METHODS: HL-60 cells were irradiated with doses 8 and 20 Gy. For
      apoptosis detection APO2.7 antigen (mitochondrial membrane specific protein)
      expression without and with permeabilization by digitonin was used. This method
      was compared with flow-cytometric analysis of cell light scattering properties
      and determination of subG1 DNA. RESULT: Cells irradiated with high dose (20 Gy)
      died rapidly by premitotic apoptosis (interphase death) from all phases of cell
      cycle. 2 hours after irradiation cells with subdiploid DNA content and cells
      stained by APO2.7 after digitonin permeabilization appeared. After 6 hours 40% of
      cells were apoptotic, nonapoptotic cells were mainly in G1-phase. Lower dose (8
      Gy) after 6 hours of irradiation caused accumulation of cells in S-phase. After
      24 hours majority of cells was in G2-phase and apoptotic cells appeared (subG1
      peak, APO2.7 with permeabilization). CONCLUSION: Data presented herein indicate
      that mitochondrial membrane protein-specific antibody APO2.7 after
      permeabilization is a useful marker for detection of early apoptotic cells dying
      by premitotic and postmitotic apoptosis.

PMID- 14661732
TI  - Inhibition of hormone secretion in GH-secreting pituitary adenomas by receptor
      subtype specific somatostatin analogues in vitro.
AB  - The aim of the study was to determine the inhibitory effects of somatostatin
      analogues with relative specificity to somatostatin receptor subtype 2 (SSTR2)
      (BIM-23197), subtype 5 (SSTR5) (BIM-23268), and their combination on GH and PRL
      secretion in acromegalic adenomas in vitro. Three types of answer were observed:
      1. In one resistant adenoma no inhibition was achieved. 2. The GH secretion in
      six adenomas was suppressed significantly more (p < 0.01 or p < 0.001 using Mann
      Whitney U-test in concentration range of 10(-12) to 10(-8) mol/l) with SSTR2
      specific analogue BIM-23197 with no additive effect of compounds combination. 3.
      In three adenomas the potency of BIM-23197 and BIM-23268 was almost equal and the
      combination of these SSTR2 and SSTR5 specific compounds had statistically
      significant additive effect (p < 0.05 or p < 0.01 in concentration range of 10(
      12) to 10(-8) mol/l). PRL secretion of five adenomas was more suppressed with
      SSTR5 specific BIM-23268 (statistically significant in concentrations 10(-10) to
      10(-8) mol/l). In conclusion the somatostatin analogue BIM-23268 had an additive
      effect on suppression of GH secretion in a subset of adenomas, where both SSTR2
      and SSTR5 were involved. This effect was not observed in the majority of tumours,
      where the inhibitory effect seems to be mediated via SSTR2 only.

PMID- 14661733
TI  - Role of epicardial QT intervals in the assessment of ventricular repolarisation
      dispersion.
AB  - The role of cardiac surface QT intervals (QTI) in assessing ventricular
      repolarisation dispersion was investigated in 10 pentobarbital-anesthetized, open
      chest sheep. Activation-recovery interval (ARI) and QTI were measured from
      multiple ECGs acquired from left ventricular epicardium, before and after
      procainamide administration (15 mg/min i.v. for 20 min). Procainamide therapy
      resulted in a significant prolongation in ARI and corrected QT interval (cQTI). A
      correlation between QTI, cQTI and ARI was found in only one animal (r = 0.78 and
      0.79 respectively, p = 0.01) before procainamide therapy. No correlation was
      found between pooled QTI and ARI dispersion from the 10 animals at baseline or
      after procainamide administration (p > 0.05). There was a moderate correlation
      between pooled cQTI and ARI dispersion (r = 0.69, p = 0.02) before procainamide
      therapy. In conclusion, epicardial QTI have no significant correlation with the
      duration of ventricular repolarisation. Epicardial QTI dispersion is not a useful
      index of repolarisation heterogeneity.

PMID- 14661734
TI  - Osmotic water permeability and regulatory volume decrease of rat thymocytes.
AB  - Rat thymocytes displayed robust regulatory volume decrease (RVD) when suspended
      in NaCl-based hypotonic Ringer solutions. The RVD of thymocytes was completely
      abolished upon replacement of external Na+ ions with K+, indicating a role of
      coupled efflux of K+ and Cl- ions as a driving force of regulatory volume
      decrease. Osmotic water permeability (Pf) measured in KCl-based hypotonic
      solutions was (1.3 +/- 1.0 x 10(-4) cm/s at 25 degrees C and was temperature
      dependent with low activation energy (Ea = 4.65 +/- 0.77 kcal/mol) characteristic
      to water transport through pores. HgCl2 and a sulfhydryl-blocking reagent, methyl
      methanethiosulphonate (MMTS), modulated the water permeability of thymocytes in a
      biphasic manner: inhibited at low dose (0.1-1 micromol/l) and restored or even
      enhanced at higher (10-100 micromol/l) concentrations. RVD paralleled the Pf: it
      was greatly suppressed at low dose of MMTS (sufficient to attenuate the water
      transport), but recovered at higher dose, when the water movement was restored.
      Therefore we suggest that thymocytes require the effective water transport for
      functional regulatory volume decrease.

PMID- 14661735
TI  - Possible metabolic pathways of conversion of formaldoxime and glyceryl trinitrate
      to NO.
AB  - The oxidation of N-hydroxylated compounds may result in production of nitrogen
      oxides, including nitric oxide (NO). Oxidation may be independent on NO-synthase.
      Production of nitrites and nitrates via NO from formaldoxime and glyceryl
      trinitrate was studied and compared. Superoxide ion, ions Fe2+ and Fe3+,
      methemoglobin and methemoglobin + NADPH + methylene blue, oxyhemoglobin and
      oxyhemoglobin + NADPH + methylene blue in the presence of atmospheric oxygen were
      used as oxidoreductive agents. Formaldoxime (triformaxime) was chosen as a newly
      recognized atypical cyclic oxime which can be converted to NO and glyceryl
      trinitrate as a well-known NO donor of quite different structure. From the
      oxidoreductive agents used, glyceryl trinitrate was not converted to nitrites or
      nitrates by Fe2+ or Fe3+ and by methemoglobin alone. Formaldoxime was resistant
      to the action of superoxide ion and methemoglobin alone. Importance of these
      possible metabolic pathways for production of NO from examined vasodilators is
      discussed.

PMID- 14661736
TI  - Immunoglobulin D enhances interleukin-6 release from the KU812 human prebasophil
      cell line.
AB  - Despite the role of secreted immunoglobulin D (IgD) remains still largely
      unknown, previous studies have suggested that secreted IgD could induce basophils
      degranulation in some allergic asthma patients. In the present study we have
      searched direct evidence of the action of IgD on KU812 cells, generally
      classified as an immature basophilic cell line. We analyzed by flow cytometry the
      capacity of IgD, purified from IgD myeloma sera, to bind KU812 cells.
      Biotinylated monomeric IgD (mIgD) and biotinylated oligomeric IgD (oIgD) could
      bind KU812 cells. Blocking experiments with others immunoglobulin isotypes showed
      that KU812 cells expressed an unspecific receptor for IgD. However, oIgD but not
      mIgD enhances the release of interleukin-6 (IL-6) from KU812 cells. On the other
      hand, mIgD and oIgD failed to induce histamine release from KU812 cells or from
      cord blood derived basophils. Since IL-6 is known to induce basophil
      differentiation, we proposed that IgD could be implicated in allergic disorders
      by stimulating IL-6 release by prebasophil cells, then IL-6 could further induce
      an autocrine maturation of the cells.

PMID- 14661737
TI  - Hypoxia increases cell death in multidrug-resistant leukemia cells. Differences
      in viability and ultrastructure between sensitive and multidrug-resistant L1210
      mouse leukemic cells under hypoxia.
AB  - The comparative study of sensitive and multidrug-resistant L1210 cells under 24
      hours of hypoxia (2% O2 and 5% CO2 at 37 degrees C) was done to see if
      differences in energetic metabolism between both cell lines are paralleled by
      differences in cellular morphology. During the dye exclusion assay the viability
      of sensitive cells was about 70 to 90%, whereas only 30 to 50% of resistant cells
      were viable. Electron microscopic study of sensitive and resistant L1210 cells
      under hypoxia has shown cells of different ultrastructural appearance in both
      cell lines. Cells with necrotic changes (swollen mitochondria, lysed cells)
      prevailed in resistant cells. The highest incidence of cells with normal or
      slightly dense mitochondria was found among the sensitive L1210 cells.
      Additionally, cells with pyknotic nuclei, shrunken cytoplasm and dense
      mitochondria, reminiscent of apoptosis, could be found sporadically, especially
      in the sensitive L1210 cell line. These results are in agreement with flow
      cytometry measurements: in resistant cells the number of necrotic cells was on
      the average 2.3 times higher than in sensitive cells. Ultrastructural differences
      and differences in the numbers of necrotic cells as measured by flow cytometry
      between sensitive and resistant L1210 cells under hypoxia are consistent with
      differences in energetic metabolism between these cell lines, as described in
      earlier studies, and document an increased cell death in the resistant L1210 cell
      line.

PMID- 14661738
TI  - Single and multiple early afterdepolarization caused by nickel in rat atrial
      muscle.
AB  - We examined the possible role of the Na-Ca exchange (NCX) in the arrhythmogenesis
      in rat atrial preparations applying microelectrode technique. In control Tyrode
      solution preparations isolated from the sinoatrial area contracted with frequency
      of 48+/-4 min(-1) (group I) or 84+/-7 min(-1) (group II). In preparation beating
      with low frequency partial inhibition of NCX by administration of Ni2+ (0.3
      mmol/l) to the bath solution caused single early afterdepolarization (EAD) on the
      15th min. During the following five minutes they were transformed into multiple
      EADs from 4 to 47 (action potentials) with general duration of 1-12 s. The
      effects were reversible. Ni2+ (0.3 mmol/l) in the preparations beating with
      higher rate (group II) did not cause multiple EADs, but after higher Ni2+
      concentration (0.5 mmol/l) single EAD was observed more often. It was concluded
      that Ca2+ overload due to partial block of the NCX can contribute to the
      development of atrial tachyarrhythmias.

PMID- 14661739
TI  - Acute-phase-dependent binding affinity of C/EBPbeta from the nuclear extract and
      nuclear matrix towards the hormone response element of the alpha2-macroglobulin
      gene in rat hepatocytes.
AB  - Interactions of nuclear extract and nuclear matrix proteins from rat hepatocytes
      with the hormone response element of the alpha2-macroglobulin gene were studied.
      By Western and South-Western blot analysis we have shown the presence of
      C/EBPbeta in the examined nuclear fractions as well as its increased binding
      affinity to the examined gene sequence during the acute-phase response. The
      results suggest that both nuclear protein fractions could participate in the
      transcriptional regulation of the alpha2-macroglobulin gene in the rat
      hepatocytes.

PMID- 14661740
TI  - Membrane-assisted solvent extraction of polychlorinated biphenyls in river water
      and other matrices combined with large volume injection-gas chromatography-mass
      spectrometric detection.
AB  - Membrane-assisted solvent extraction was applied to the determination of
      polychlorinated biphenyls (PCBs) in aqueous samples. The apparatus of membrane
      assisted solvent extraction consisted of a 20 ml headspace vial which was filled
      with 15 ml of the aqueous sample. The membrane bag was placed into the vial and
      the extraction took place in an agitator. After extraction, the analytes were
      transferred into the inlet of a gas chromatograph by large volume injection. A
      mass-selective detector was used. The whole procedure was fully automated. The
      work included optimization of the extraction conditions (stirring rate and
      extraction time) and the influence of matrix effects like salt addition and the
      presence of organic solvents was studied. Calibration was performed using
      injection volumes of 100 and 400 microl. Several parameters like linearity and
      reproducibility of the procedure were determined. At optimized conditions
      detection limits in the ng/l range were achieved. The effectiveness of the method
      towards real samples was tested by analyzing river water, white wine and apple
      juice.

PMID- 14661741
TI  - Simultaneous determination of degradation products of nonylphenol polyethoxylates
      and their halogenated derivatives by solid-phase extraction and gas
      chromatography-tandem mass spectrometry after trimethylsilylation.
AB  - An efficient method for the simultaneous determination of the degradation
      products of nonylphenol polyethoxylates (NPnEOs, n = number of ethoxy units),
      i.e., nonylphenol (NP), NPnEOs (n = 1-3), nonylphenoxy carboxylic acids (NPnECs,
      n = 1-2, number of ethoxy units plus an acetate) and their halogenated
      derivatives (XNP, XNP1EO and XNP1EC; X = Br or Cl), in water samples were
      developed. After trimethylsilylation with N,O-bis(trimethysilyl)acetamide, all
      the analytes were determined by gas chromatography-tandem mass spectrometry (GC
      MS-MS) with electron ionization (EI). The ion peaks of [M - 85]+ of the
      derivatives were selected as precursor ions and their product ions showing the
      highest intensities were used for the quantitative analysis. The instrumental
      detection limits were in the range from 2.1 to 11 pg. The recoveries of the
      analytes from the water samples were optimized by using solid-phase extraction
      (SPE). The deuterated reagents of octylphenol, octylphenol monoethoxylate and
      octylphenoxyacetic acid were used as the surrogates. The method detection limits
      (500 ml water sample) using C18 SPE were from 2.5 to 18 ng/l. The recoveries from
      spiked pure water and the environmental water samples were greater than 78%. The
      method was successfully applied to environmental samples. Remarkably, the
      concentrations of the halogenated compounds (CINP, CINP1EO and BrNP1EO) were
      detected at the hundreds of ng/l levels in the Neya river.

PMID- 14661742
TI  - Analysis of multiple pesticide residues in tobacco using pressurized liquid
      extraction, automated solid-phase extraction clean-up and gas chromatography
      tandem mass spectrometry.
AB  - A new method was developed for the analysis of pesticide residues in tobacco. The
      objective was to significantly increase the number of samples that can be
      processed by the laboratory and to enable the extension of the current coverage
      to additional pesticides. A new analytical approach was therefore defined based
      on two main axes, the automation of the sample preparation and the selectivity of
      the analyte detection using tandem mass spectrometry. This latter aspect reduces
      the stringency of the requirements placed on the clean-up of the extracts and on
      the chromatographic resolution when less selective detectors are used. The
      extraction of the analytes from the matrix is performed using the pressurized
      liquid extraction technique. Tobacco samples are extracted at elevated
      temperature and pressure (100 C and 100 atm; 1 atm = 101,325 Pa) using acetone as
      an extraction solvent. The resulting extract is then concentrated using a Vortex
      evaporator. Three different solid-phase extraction (SPE) procedures, adjusted to
      the chemical properties of the different active ingredients to be measured, are
      applied to the concentrated extract, thus leading to three extract fractions. The
      first fraction contains such main classes of active ingredients as
      organohalogenated and 2,6-dinitroaniline compounds while the second one collects
      the organophosphorus and acylalanines residues; these two fractions are analyzed
      by capillary gas chromatography coupled to tandem mass spectrometry using
      negative chemical ionization and electron impact ionization in the positive mode,
      respectively. The third extract fraction gathers the N-methylcarbamates residues
      which are analyzed by HPLC with post-column derivatization and fluorescence
      detection. The different sample preparation stages from extraction to SPE clean
      up have been automated through the use of recent analytical technologies. In
      combination with the analysis by tandem mass spectrometry, this provided a
      potential for a high sample throughput.

PMID- 14661743
TI  - Evaluation of multiple solid-phase microextraction as a technique to remove the
      matrix effect in packaging analysis for determination of volatile organic
      compounds.
AB  - Multiple solid-phase microextraction (SPME) is an useful technique for the direct
      quantification of solid samples removing any matrix effect. The volatile organic
      compounds formed in the extrusion-coating process of multilayer packaging
      materials have already been quantified by multiple HS-SPME coupled to gas
      chromatography (GC)-mass spectrometry (MS) using volatile organic compound (VOC)
      solutions in hexadecane for calibration. In this article, water is proposed as
      solvent to prepare the calibration solutions because it provides a shorter
      calibration time, better linearity, better reproducibility, and lower detection
      limits than hexadecane. Besides, the extraction of VOCs from aqueous solutions is
      exhaustive and avoids the extrapolations needed to calculate the total peak
      areas, as they can be calculated as the sum of the individual areas of each
      extraction. Finally, it is checked whether the two solvents provide the same mean
      values for the total peak areas.

PMID- 14661744
TI  - Modeling of the separation of two enantiomers using a microbore column.
AB  - A microbore column packed with Chiralcel OB (cellulose tribenzoate coated silica)
      was used for the measurement of the single and competitive equilibrium-isotherm
      data of the 1-indanol enantiomers by frontal analysis. The amount of sample
      needed for the isotherm data acquisition was about 20 times less than that
      required with a conventional column. The data obtained were fitted to different
      single and competitive isotherm models. Both the single and the competitive data
      sets fitted best to the same Bilangmuir (BL) isotherm model with small
      differences in the numerical values of the parameters. The best fitted Bilangmuir
      single and competitive isotherm models were used to predict the overloaded
      experimental profiles of both pure enantiomers, of the racemic mixture, and of
      different enantiomeric mixtures. All the calculated profiles were in excellent
      agreement with the experimental ones. This agreement confirms that in many chiral
      separations, the competitive isotherms can be derived from data acquired from the
      mere racemic mixture with a sufficient accuracy for a correct prediction of the
      band profiles of all kinds of enantiomer mixtures, making possible the computer
      assisted optimization of the experimental conditions.

PMID- 14661745
TI  - Evaluation of liquid chromatography column retentivity using macromolecular
      probes. III. Partition properties of C18 phases traced by polymers.
AB  - Application of polymeric probes was proposed for evaluation of partition
      properties of the high performance liquid chromatographic stationary phases. The
      approach was tested with selected silica gel C-18 column packings. Polystyrene
      (PS) and poly(n-butyl methacrylate) (PnBMA) narrow molar mass standards of low
      polarity were applied to avoid adsorption of macromolecules on silanols and other
      polar groups present within column packings. Polar eluent components further
      reduced contingency of silanophilic interactions. The major eluent component was
      dimethylformamide (DMF), a thermodynamically poor solvent for polymer probes,
      which strongly promoted enthalpic partition of macromolecules in favor of the C18
      bonded phase. Methyl ethyl ketone (MEK) and diethyl malonate (DEM) were also
      tested as the partition promoting eluent components. With polystyrenes, MEK was
      rather inefficient as a partition promoter while DEM was similarly active as DMF.
      A thermodynamically good solvent for polymer probes, viz. tetrahydrofuran (THF)
      was added to eluent to reduce and control the extent of partition. The
      differences in elution behavior of column tested indicate their unlike partition
      properties.

PMID- 14661746
TI  - Association behaviour of lignins and lignin model compounds studied by
      multidetector size-exclusion chromatography.
AB  - SEC elution curves of spruce milled wood lignin (MWL) and guaiacyl lignin polymer
      models (G-DHPs) in N,N-dimethylformamide (DMF) exhibited a bimodal elution
      profile. Light scattering measurements indicated that these elution profiles were
      due to association effects between the molecules. This became apparent from the
      determination of high molar masses in the range 10(5)-10(8) g/mol. To study this
      effect, MWL and DHP were fractionated by precipitation in tetrahydrofuran (THF).
      The THF-insoluble fractions were found to be the fractions corresponding to the
      apparent high molar mass part of the DMF elution profiles. The THF-soluble
      fractions proved to be the less-associated fractions, with lower apparent
      molecular mass. The individual fractions proved to be rather stable in DMF.
      Accordingly, the bimodal elution profiles of the starting materials were not the
      result of an equilibrium between associated and molecular dispersed molecules but
      of different structures exhibiting a specific and stable association pattern. The
      different fractions were further characterised by SEC in THF after acetylation to
      determine molar masses in molecular disperse solutions.

PMID- 14661747
TI  - Determination of lincomycin and tylosin residues in honey using solid-phase
      extraction and liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry.
AB  - An analytical method for the determination of residues of the antibiotic drugs
      lincomycin and tylosin in honey was developed. The procedure employed a solid
      phase extraction for the isolation of lincomycin and tylosin from diluted honey
      samples. The antibiotic residues were subsequently analyzed by reversed-phase
      HPLC with atmospheric pressure chemical ionization mass spectrometric detection.
      Average analyte recoveries for lincomycin and tylosin ranged from 84 to 107% in
      replicate sets of honey samples fortified with drug concentrations of 0.01, 0.5,
      and 10 microg/g. The method detection limits were determined to be 0.007 and 0.01
      microg/g for lincomycin and tylosin, respectively.

PMID- 14661748
TI  - Development and validation of a liquid chromatography-ultraviolet absorbance
      detection assay using derivatisation for the novel marine anticancer agent ES-285
      x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage
      form.
AB  - ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] is a novel
      investigational anticancer agent, which has shown in vitro and in vivo cytotoxic
      activity against various tumor cell lines with selectivity for certain solid
      tumors. The pharmaceutical development of ES-285 x HCl warranted the availability
      of an assay for the quantification and purity determination of ES-285 x HCl
      active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A
      liquid chromatographic method (LC) comprising of derivatisation of ES-285 x HCl
      with phenylisothiocyanate and UV-detection was developed. The method was found to
      be linear, precise and accurate. The assay also proved selectivity as determined
      by analysing ES-285 x HCl in combination with 15 analogues and in combination
      with hydroxypropyl-beta-cyclodextrin, the excipient used in the lyophilised
      pharmaceutical dosage form. Stress testing showed that the degradation products
      were separated from the parent compound, confirming its stability indicating
      capacity. The method was found robust as determined with design of experiments
      (DoE), which made it possible to predict system suitability responses in worst
      case experimental conditions and to define criteria for system suitability
      testing.

PMID- 14661749
TI  - Separation of anions by ion-interaction chromatography with a novel
      cationic/zwitterionic eluent.
AB  - Inorganic and organic anions can be separated on an ordinary silica C18 column
      using a mobile phase containing tetrabutylammonium hydroxide (TBAH) and an
      aminosulfonic acid zwitterion reagent (MOPS). The pH of this eluent is close to 7
      and the background conductivity is about 50 microS, which is low enough to permit
      anion analyte detection by direct conductivity. Linear calibration curves were
      obtained for the six anions studied and detection limits ranged from 0.075 to
      0.15 mg/l (ppm) for the five inorganic anions. The method was applied to the
      determination of water-soluble anions in aerosol samples at concentrations as low
      as 0.3 mg/l.

PMID- 14661750
TI  - Suppressor current switching: a simple and effective means to reduce background
      noise in ion chromatography.
AB  - Background noise in ion chromatography with suppressed conductivity detection was
      significantly reduced for the period of time when the electric current to an
      anion self regenerating suppressor (ASRS) running in the recycle mode was turned
      off. With high capacity AS11-HC columns, it was possible to maintain current free
      conditions from the beginning of the run past the chloride peak, which enables
      routine high sensitivity analysis of early to mid eluting peaks. This suppressor
      current switching was utilized for the analysis of bromate in drinking water with
      large volume injection using on-line removal of chloride by an On-Guard Ag+
      cartridge. The method detection limit (MDL) was 0.21 microg/l in fortified
      reagent water. Coelution of bromate with an unknown compound was observed, but it
      was solved by the optimization of gradient program.

PMID- 14661751
TI  - Analysis of quantization error in high-precision continuous-flow isotope ratio
      mass spectrometry.
AB  - High-precision isotope ratio mass spectrometry (IRMS) systems are equipped with
      digitizers that deliver effective maximum digitization depths of 16 to 24 bits;
      however, there are no analyses of the proper board depth required to retain high
      precision in continuous-flow techniques. We report an experimental and
      theoretical evaluation of quantization error in continuous-flow IRMS (CF-IRMS).
      CO2 samples (100 pmol-30 nmol) were injected into a gas chromatography combustion
      IRMS system (GC-CIRMS). The analog signal was digitized by high precision, 24-bit
      ADC boards at 10 Hz, and was post-processed to simulate 12, 14, and 16-bit data
      sets. Delta13Cpdh values were calculated for all data sets by the conventional
      "summation" method or by curve-fitting the chromatographic peaks to the
      exponentially modified Gaussian (EMG) function. Benchmarks of S.D.(delta13Cpdh) =
      0.3, 0.6, and 1.0/1000 were considered to assess precision. In the presence of
      significant quantization noise, curve-fitting required several-fold less CO2 than
      the summation method to reach a given benchmark. We derived an equation to
      describe the theoretical limitations of precision for the summation method as a
      function of CO2 admitted to the source and the step size of the boards. Theory
      was in close agreement with the observed lower limit of precision for the
      simulated 16-bit data set. Curve-fitting achieved a precision of S.D. <0.3/1000
      for injections 20-fold smaller than summation for CO2 samples collected on an
      IRMS with 16-bit resolution. By mitigating the impact of quantization noise,
      curve-fitting expands the dynamic range within a single run to include lower
      analyte levels, and effectively reduces the need for high pumping capacities and
      high precision ADC boards.

PMID- 14661752
TI  - High-performance liquid chromatography-tandem mass spectrometry with a new
      quadrupole/linear ion trap instrument.
AB  - The use of a new hybrid quadrupole/linear ion trap known as the Q TRAP offers
      unique benefits as a LC-MS-MS detector for both small and large molecule
      analyses. The instrument combines the capabilities of a triple quadrupole mass
      spectrometer and ion trap technology on a single platform. Product ion scans are
      conducted in a hybrid fashion with the fragmentation step accomplished via
      acceleration into the collision cell followed by trapping and mass analysis in
      the Q3 linear ion trap. This results in triple quadrupole fragmentation patterns
      with no inherent low molecular mass cutoff. In-trap fragmentation is also
      possible in order to provide triple MS (MS3) capabilities. There are also several
      scan modes that are not possible on conventional instruments that enable
      identification of analytes within complex biological matrixes for subsequent high
      sensitivity product ion scans. This report will describe the new hybrid
      instrument and the principles of operation, and also provide examples of the
      unique scan modes and capabilities of the Q TRAP for LC-MS-MS detection in
      metabolism identification.

PMID- 14661753
TI  - Using accurate mass electrospray ionization-time-of-flight mass spectrometry with
      in-source collision-induced dissociation to sequence peptide mixtures.
AB  - Although data-dependent LC-MS-MS with database searching has become au courant
      for identifying proteins, the technique is constrained by duty-cycle inefficiency
      and the inability of most tandem mass analyzers to accurately measure peptide
      product ion masses. In this work, a novel approach is presented for simultaneous
      peptide fragmentation and accurate mass measurement using in-source collision
      induced dissociation (CID) on electrospray ionization (ESI)-time-of-flight (TOF)
      MS. By employing internal mass reference compounds, mass measurement accuracy
      within +/-5 ppm for tryptic peptide precursors and +/-10 ppm for most sequence
      specific product ions was consistently achieved. Analysis of a complex solution
      containing several digested protein standards did not adversely affect instrument
      performance.

PMID- 14661754
TI  - Quantification of the anticancer agent STI-571 in erythrocytes and plasma by
      measurement of sediment technology and liquid chromatography-tandem mass
      spectrometry.
AB  - An isocratic high-performance liquid chromatographic method coupled to tandem
      mass spectrometry for the quantification of the revolutionary and promising
      anticancer agent STI-571 (tradenames Gleevec, Glivec, Imatinib) in blood plasma
      and red blood cells (RBCs) is described. The method involves measurement of
      sediment technology for RBCs and a subsequent single protein precipitation step
      by the addition of acetonitrile to both the RBC isolate and plasma. The sample
      mixture was centrifuged (10 min, 3600 g), and the supernatant filtered through a
      HPLC filter (0.45 microm). The analytes of interest, STI-571 and the internal
      standard [2H8]STI-571 were eluted on a Waters Symmetry C18 column (50x2.1 mm
      I.D., 3.5 microm particle size) using a methanol-0.05% ammonium acetate (72:28,
      v/v) mixture. STI-571 and [2H8]STI-571 were detected by electrospray tandem mass
      spectrometry in the positive mode, and monitored in the multiple reaction
      monitoring transitions 494>394 and 502<394, respectively. The lower limit of
      quantitation of STI-571 was 2.1 ng/ml in RBCs and 1.8 ng/ml in plasma. The
      recovery from both plasma and RBCs was between 65 and 70%. The method proved to
      be robust, allowing simultaneous quantification of STI-571 in RBCs and plasma
      with sufficient precision, accuracy and sensitivity and is useful in monitoring
      the fate of this signal transduction inhibitor in whole blood of cancer patients.

PMID- 14661755
TI  - Determination of nicotine and cotinine in rat plasma by liquid chromatography
      tandem mass spectrometry.
AB  - A method was developed for the efficient determination of nicotine and cotinine
      in rat plasma samples originating from nicotine exposure studies. Nicotine and
      cotinine were extracted from plasma samples with dichloromethane and concentrated
      to minimum volume with nitrogen stream. The volatility of nicotine was prevented
      by the addition of hydrochloric acid to the organic solvent during evaporation.
      The samples were analysed using liquid chromatography with triple quadrupole mass
      spectrometry. For quantification, the deuterated internal standards were added
      and the most intensive MS-MS ion of the analyte and internal standards were
      monitored. For confirmatory analysis, two specific MS-MS ions, viz. m/z 132 and
      106 for nicotine and m/z 80 and 98 for cotinine, were monitored and the ratios
      between the ions were calculated and compared with those of standards. The ratios
      have to be within the tolerances of the EU criteria. The limit of identification
      of the developed method was 1 microg/l. The repeatability ranged from 5 to 12%
      (R.S.D.) for nicotine and from 3 to 5% for cotinine at the concentration level of
      1-60 microg/l (n = 4).

PMID- 14661756
TI  - Rapid detection and identification of angiotensin-converting enzyme inhibitors by
      on-line liquid chromatography-biochemical detection, coupled to electrospray mass
      spectrometry.
AB  - An analytical method based on on-line liquid chromatography-biochemical detection
      (LC-BCD) coupled to electrospray mass spectrometry was developed for the
      detection and identification of angiotensin-converting enzyme (ACE) inhibitors in
      complex mixtures, such as hydrolyzed whey proteins. ACE inhibitory activity was
      detected by coupling a homogeneous, substrate conversion based bioassay on-line
      to high-performance liquid chromatography (HPLC). Chemical information was
      obtained by directing part of the HPLC effluent towards a mass spectrometer.
      After correlating the biochemical and chemical data, the accurate molecular
      masses of the bioactive peptides were used as search queries in protein
      databases. Combined with the recorded mass spectrometry (MS)-MS fingerprints,
      bioactive peptides were selected from the database search results. The results of
      LC-BCD-MS analyses were verified by establishing a bioactivity balance. Reference
      samples, containing several peptides at concentration levels similar to those
      observed in the hydrolyzed milk samples, were analyzed by LC-BCD-MS. High
      recoveries of biological activity were obtained, indicating that the correct ACE
      inhibitors were identified and that no co-elution of significantly bioactive
      molecules had occurred. Approximately, 30 ACE inhibitors were detected and
      identified. IC50 values of ACE inhibitors, reported in literature, ranged between
      43 and 580 microM.

PMID- 14661757
TI  - On-line turbulent-flow chromatography-high-performance liquid chromatography-mass
      spectrometry for fast sample preparation and quantitation.
AB  - A sensitive and selective liquid chromatography-mass spectrometry method has been
      developed for the simultaneous identification and quantitation of drug substances
      and metabolites in rat plasma. The method combines on-line turbulent-flow
      chromatography, high-performance liquid chromatography and mass spectrometry.
      This combination is considered to be a new approach suitable for fast bio
      analysis in drug discovery. Dextromethorphan, and its two metabolites,
      dextrorphan and 3-methoxymorphinan served as model substances. The analytes
      present in plasma were collected on a Cyclone column using turbulent-flow
      chromatography and were subsequently transferred on-line to and focused on an X
      Terra MS C8 column. The analytes were eluted by a linear gradient and detected by
      a fast scanning mass spectrometer. The detector response was quadratic and the
      dynamic range was estimated to be 0.5-100 ng/ml plasma or 12.5 pg to 2.50 ng
      injected into the system.

PMID- 14661758
TI  - Chiral liquid chromatography-mass spectrometry for high-throughput screening of
      enzymatic racemase activity.
AB  - In finding suitable biocatalysts for processes in chemical industry, expression
      libraries are constructed containing typically >10,000 clones. Search for a
      desired activity is done by examination of all the clones in one or more
      libraries using a high-throughput screening assay. Here we describe a method for
      the screening of the enzymatic racemase activity of clones from an expression
      library on alpha-amino-epsilon-caprolactam (ACL) using a fast chiral LC
      separation and ionspray-MS as the detection technique. After substrate incubation
      with S-ACL, the 96-well microplates were centrifuged to remove cell material. The
      conversion of S-ACL to R-ACL was monitored by quantitation of the R-ACL
      enantiomer. Separation of the two ACL enantiomers was performed on a Crownpak CR+
      column within 1 min. A Gilson 215 autosampler with a 889 multiple injection probe
      was used for injecting the samples into the LC system. The total analysis time
      for a 96-well microplate was 56 min. The MS was operated in the positive-ion mode
      using selected ion monitoring at m/z 129 [M+H]+ of ACL. Using this method over
      12,000 samples were analyzed without loss in performance of the system. The LC
      column remained stable without loss of resolution and the MS system did not show
      loss in sensitivity throughout the screening. Inter-day reproducibility was
      within 15%.

PMID- 14661759
TI  - On-line identification of tropane alkaloids from Erythroxylum vacciniifolium by
      liquid chromatography-UV detection-multiple mass spectrometry and liquid
      chromatography-nuclear magnetic resonance spectrometry.
AB  - The bark of catuaba (Erythroxylum vacciniifolium Martius, Erythroxylaceae), a
      tree native to the northern part of Brazil, was investigated for its alkaloid
      content. With the aim of obtaining preliminary structure information on-line, the
      alkaloid extract was analysed by high-performance liquid chromatography coupled
      to diode array UV detection, to mass spectrometry and to nuclear magnetic
      resonance. Interpretation of on-line spectroscopic data obtained from this
      extract led to structural elucidation of six new alkaloids and partial
      identification of 18 potentially original alkaloids bearing the same tropane
      skeleton esterified in positions 3 and 6 by 1-methyl-1H-pyrrol-2-carboxylic acid
      and/or 4-hydroxy-3,5-dimethoxybenzoic acid.

PMID- 14661760
TI  - Novel approach to the determination of structurally similar hydroxamate
      siderophores by column-switching capillary liquid chromatography coupled to mass
      spectrometry.
AB  - In this study a new approach to determine three different siderophores
      (ferrichrome, ferrichrysin, ferricrocin) in natural soil solutions as well as in
      cultures of fungi is presented. The method includes enrichment of the analytes on
      a short pre-column, packed with C18 material, and subsequent highly selective
      separation of the analytes on a capillary porous graphitic carbon (PGC) column.
      In contrast to normal C18 packing materials, porous graphitic carbon offers
      chromatographic resolution between the three very similar analytes. The
      selectivity of the method is enhanced even further by the electrospray ionization
      (ESI) mass spectrometric detection. The combination of a short pre-column and a
      packed capillary separation column results in a method with high sensitivity.
      Reported detection limits, defined as the concentration giving the signal-to
      noise ratio 3:1, is 27.7 pM for ferrichrome, 46.1 pM for ferricrocin and 37.4 pM
      for ferrichrysin.

PMID- 14661761
TI  - Analysis of steroid hormones in effluents of wastewater treatment plants by
      liquid chromatography-tandem mass spectrometry.
AB  - This paper presents the development of an analytical procedure for the
      determination of two sexual steroid hormones: 17beta-estradiol and estrone, and
      the synthetic contraceptive estrogen, 17alpha-ethynylestradiol in effluents of
      wastewater treatment plants. Samples are extracted via solid-phase extraction
      using C18 cartridges. Extracts in ethyl acetate are then purified with a liquid
      liquid separation with aqueous sodium chloride, then with a clean-up on a
      Florisil cartridge. Steroids are analyzed using an LC-MS-MS ion trap system.
      Internal quantification with the corresponding deuterated steroids leads to
      limits of quantification at 5 ng/l for estrone and 10 ng/l for estradiol and
      ethynylestradiol. In mineral spiked water, recoveries are 91% for 17beta
      estradiol, 97% for estrone and 87% for 17alpha-ethynylestradiol and RSDs are 15%
      for 17beta-estradiol, 11% for estrone and 23% for 17alpha-ethynylestradiol.

PMID- 14661762
TI  - Screening for cyanobacterial hepatotoxins, microcystins and nodularin in
      environmental water samples by reversed-phase liquid chromatography-electrospray
      ionisation mass spectrometry.
AB  - Water samples taken from 93 freshwater and brackish water locations in Aland (SW
      Finland) in 2001 were analysed for biomass-bound microcystins and nodularin,
      cyanobacterial peptide hepatotoxins, by liquid chromatography-mass spectrometry
      (LC-MS) in selected ion recording (SIR) and multiple reaction monitoring modes,
      HPLC-UV, and enzyme-linked immunosorbent assay (ELISA). The extracted toxins were
      separated on a short C18 column with a gradient of acetonitrile and 0.5% formic
      acid, and quantified on a Micromass Quattro Micro triple-quadrupole mass
      spectrometer with an electrospray ion source operated in the positive SIR or scan
      mode. An injection of 50 pg of microcystin-LR, m/z 995.5, on column gave a signal
      to-noise ratio of 17 (peak-to-peak) at the chosen SIR conditions. In-source or MS
      MS fragmentation to m/z 135.1, a fragment common to most microcystins and
      nodularin, was used for confirmatory purposes. Microcystins with a total toxin
      concentration equal to or higher than 0.2 microg l(-1) were confirmed by all
      three methods in water samples from 14 locations. The highest toxin concentration
      in a water sample was 42 microg l(-1). The most common toxins found were
      microcystins RR, LR and YR with different degrees of demethylation (non-, mono-
      or didemethylated). Parallel results achieved with ELISA and HPLC-UV were
      generally in good agreement with the LC-MS SIR results.

PMID- 14661763
TI  - Analysis of acrylamide in food by isotope-dilution liquid chromatography coupled
      with electrospray ionization tandem mass spectrometry.
AB  - A confirmatory method for the determination of low levels of acrylamide in
      different food products is presented. The method entails extraction of acrylamide
      with water, precipitation of matrix constituents with acetonitrile, and two clean
      up steps consecutively over Isolute Multimode and cation-exchange cartridges. The
      final extract is analyzed by liquid chromatography (LC) coupled to positive
      electrospray ionization tandem mass spectrometry employing [13C3]-acrylamide as
      internal standard. For the chromatographic step, a LC column based on a
      polymethacrylate gel is employed which shows good retention of acrylamide under
      isocratic flow conditions (k' = 1.2). Mass spectral acquisition is done by
      selected reaction monitoring, choosing the characteristic transitions m/z 72-
      >55, 72-->54 and 72-->27. In-house validation data for breakfast cereals and
      crackers show good precision of the method, with intra- and interassay variation
      below 10%. The limits of detection for crackers and breakfast cereals,
      respectively are estimated at 15 and 20 microg/kg, and recoveries of fortified
      samples ranged between 58 and 76%. Furthermore, the method is applicable to a
      number of different food products, including biscuits, crisp bread, wafers,
      confectionery cocoa liquor, and nuts. Finally, the good results obtained in
      several small-scale interlaboratory tests provided additional confidence in the
      performance of the method.

PMID- 14661764
TI  - Determination of fluorinated surfactants and their metabolites in sewage sludge
      samples by liquid chromatography with mass spectrometry and tandem mass
      spectrometry after pressurised liquid extraction and separation on fluorine
      modified reversed-phase sorbents.
AB  - An analytical method was elaborated for simultaneous extraction and determination
      of fluorinated anionic and non-ionic surfactants in sewage sludge. Surfactant
      compounds were determined by liquid chromatography-mass spectrometry (LC-MS)
      after Soxhlet extraction, hot steam extraction and pressurised liquid extraction
      (PLE) using spiked sludge samples. PLE in a multiple-step procedure consisting of
      sequential use of ethyl acetate-dimethylformamide and methanol-phosphoric acid
      resulted in the most efficient extraction procedure. Quantitative analyses of the
      fluorinated anionic perfluorooctanesulfonate (PFOS) and the partly fluorinated
      non-ionic alkylpolyglycol ether (FAEO) surfactants were performed by selected ion
      monitoring LC-MS. Electrospray ionisation or atmospheric pressure chemical
      ionisation in negative or positive mode was performed. Recoveries between 105 and
      120% could be reached. No PFOS and non-ionic FAEO surfactants in concentrations
      higher than 6 or 10 mg kg(-1) dry matter were observed in real environmental
      samples. Therefore aerobic and anaerobic biodegradation was performed to
      investigate the fate of fluorinated surfactants reaching wastewaters. Biological
      wastewater treatment in laboratory scale under aerobic or anaerobic conditions
      led to an elimination by biodegradation.

PMID- 14661774
TI  - Clinical scholars defined.

PMID- 14661775
TI  - The 2003 Eleanor Clarke Slagle Lecture. Chaotic occupational therapy: collective
      wisdom for a complex profession.
AB  - In the tradition of Mosey's (1985) Eleanor Clarke Slagle lecture (p. 504) as a
      road map to where this presentation is going, I will present a short preface and
      first, talk about her story and our professional identity; second, use chaos
      theory as a way to look at occupation; third, introduce you to Charlotte's Web of
      Chaos; fourth, make some conclusions about chaos and occupational therapy; fifth,
      do an ending to this telling, and; sixth, do a summary and closing.

PMID- 14661776
TI  - The nature of clinical reasoning with groups: a phenomenological study of an
      occupational therapist in community mental health.
AB  - OBJECTIVE: The purpose of this paper is to examine the clinical reasoning of an
      occupational therapist in group practice in mental health. It emerged from a
      larger phenomenological study of expert occupational therapy practitioners in
      community mental health. METHOD: Data were gathered through intensive, semi
      structured interviews with 1 day of participant observation. Analysis was an
      iterative process in which emerging themes were identified for reflection and
      interpretation. Previously established categories of clinical reasoning were used
      as a structure for describing the results. RESULTS: A rich description of
      clinical reasoning in psychosocial task groups is presented using interactive,
      narrative, conditional, and pragmatic reasoning. The gestalt of community
      practice is illustrated, as the therapist describes the multiple levels of
      consciousness used in her consideration of, and response to, clients within the
      context of the larger environment. CONCLUSION: This study suggests that an
      examination of occupational therapy with psychosocial groups is a rich area for
      research to extend our understanding of clinical reasoning in occupational
      therapy.

PMID- 14661777
TI  - Introducing OTseeker (Occupational Therapy Systematic Evaluation of Evidence): a
      new evidence database for occupational therapists.
AB  - This clinical scenario illustrates how OTseeker can be used by occupational
      therapists to locate research that may inform clinical decisions. Beyond the
      clinical arena, this database also has potential to greatly enhance the ability
      of researchers to perform systematic reviews of RCTs and eventually, development
      of clinical guidelines. In conclusion, OTseeker is a new Web-based database that
      provides fast access to evidence of therapeutic effectiveness for clinicians,
      academics, and students, as well as consumers and providers of occupational
      therapy services. OTseeker will be able to be used by clinicians to guide dinical
      practice, by researchers to perform systematic reviews of RCTs, by students, and
      by consortiums of stakeholders to develop evidence-based guidelines for
      occupational therapy practice.

PMID- 14661778
TI  - Philosophy of professional education (2003 statement).

PMID- 14661779
TI  - Scholarship and occupational therapy (2003 concept paper).

PMID- 14661780
TI  - The purpose and value of occupational therapy fieldwork education (2003
      statement).

PMID- 14661781
TI  - The viability of occupational therapy assistant education.

PMID- 14661782
TI  - Guidelines for documentation of occupational therapy (2003).

PMID- 14661783
TI  - Physical agent modalities: a position paper (2003).

PMID- 14661784
TI  - Applying sensory integration framework in educationally related occupational
      therapy practice (2003 statement).
AB  - Based on the educational team recommendations, occupational therapists and
      occupational therapy assistants working in educationally related settings provide
      services to students who are eligible for Section 504 or special education under
      IDEA and need occupational therapy to benefit from their education program. It is
      the occupational therapist's responsibility to develop an intervention plan based
      on the student's needs and the therapist's professional knowledge base. The
      occupational therapist chooses and applies any frame of reference within the
      domain and process of occupational therapy. Regardless of the frame of reference
      utilized, the desired outcome of occupational therapy services is always
      engagement in occupations that allows participation in a student's daily life.
      When students demonstrate deficits in sensory integration that contribute to a
      significant and documented discrepancy in their skills within their educational
      program, the use of a sensory integrative approach may be one frame of reference
      for, intervention chosen by the occupational therapist.

PMID- 14661785
TI  - Specialized knowledge and skills in eating and feeding for occupational therapy
      practice.

PMID- 14661786
TI  - Three-dimensional deformation field measurement with digital speckle correlation.
AB  - Digital speckle correlation is based on a detailed analysis of changes in speckle
      images that are recorded from laser-illuminated rough surfaces. The two in-plane
      components are obtained by cross-correlation of corresponding subimages, a method
      also known as digital speckle photography. The local gradient of the hitherto
      inaccessible out-of-plane component is determined from the characteristic
      dependence of the speckle correlation on the spatial frequency. A detailed
      experimental study is carried out to analyze the new technique for systematic and
      random measuring errors. For moderate decorrelation the accuracy of the out-of
      plane measurement is better than lambda/10 and thus comparable with
      interferometric techniques. Yet the extremely simple and robust optical setup is
      suited to nondestructive-testing applications in harsh environments. The quality
      of the deformation maps is demonstrated in a practical application.

PMID- 14661787
TI  - Zero reference signal for displacement measuring systems by use of speckle.
AB  - An optical method for generating a reference signal for an incremental
      displacement measurement system is proposed. We achieved this zero reference
      signal by comparing two speckle patterns arriving from two symmetric diffusers,
      which are used as natural random codes that are identical only when the reading
      head is located equidistantly between the diffusers. The comparison of the
      speckles is obtained either by interference, as in a Michelson interferometer, or
      by intensity correlations.

PMID- 14661788
TI  - Simulation of light propagation by local spherical interface approximation.
AB  - A new local elementary interface approximation is introduced for the modeling of
      wave propagation through interfaces between homogeneous media. The incident wave
      and the surface profile are approximated locally by a spherical wave and a
      spherical surface, respectively. The wave field travels through the modulated
      structure according to the laws of geometrical optics, being refracted by the
      surface and propagating to the output plane locally as a geometric spherical
      wave. Diffraction theory is applied to propagate the field from the output plane
      onwards. We provide comparisons of the method with the thin-element
      approximation, the local plane-wave and interface approach, and rigorous
      diffraction theory using a sinusoidal surface-relief grating as an example. We
      illustrate the power of the new method by applying it to the analysis of a
      diffractive beam splitter.

PMID- 14661789
TI  - Enhanced confined light transmission by single subwavelength apertures in
      metallic films.
AB  - The diffraction of light that emerges from a metallic circular aperture is
      studied. Near- and far-field results are presented. Spectral angular transmitted
      intensities are performed versus the incident wavelength for four kinds of
      aperture. It is shown that, for a definite configuration, a large enhancement of
      transmission--compared with the basic case of a single hole--occurs combined with
      a spectacular angular confinement of light. Such effects are, for example, of
      great interest in optical near-field microscopy for which the probe is a
      nanosource.

PMID- 14661790
TI  - Polarization-dependent loss and birefringence in long-period fiber gratings.
AB  - Widely used descriptions and relationships for birefringence and polarization
      dependent loss (PDL), developed primarily for ultraviolet-induced long-period
      fiber gratings (LPFGs) written in optical fiber, can be invalid for other types
      of LPFG. The understanding of PDL is expanded to include LPFGs with birefringence
      in the core only, in the cladding only, and in both the core and the cladding.
      Equations that link resonant wavelength separation, one factor that determines
      PDL, and birefringence for the three categories are presented, along with
      relevant approximations. Measurement results for two LPFGs fabricated by
      different techniques are presented that illustrate the effect of birefringence on
      PDL.

PMID- 14661791
TI  - Grating-assisted demodulation of interferometric optical sensors.
AB  - Accurate and dynamic control of the operating point of an interferometric optical
      sensor to produce the highest sensitivity is crucial in the demodulation of
      interferometric optical sensors to compensate for manufacturing errors and
      environmental perturbations. A grating-assisted operating-point tuning system has
      been designed that uses a diffraction grating and feedback control, functions as
      a tunable-bandpass optical filter, and can be used as an effective demodulation
      subsystem in sensor systems based on optical interferometers that use broadband
      light sources. This demodulation method has no signal-detection bandwidth limit,
      a high tuning speed, a large tunable range, increased interference fringe
      contrast, and the potential for absolute optical-path-difference measurement. The
      achieved 40-nm tuning range, which is limited by the available source spectrum
      width, 400-nm/s tuning speed, and a step resolution of 0.4 nm, is sufficient for
      most practical measurements. A significant improvement in signal-to-noise ratio
      in a fiber Fabry-Perot acoustic-wave sensor system proved that the expected
      fringe contrast and sensitivity increase.

PMID- 14661792
TI  - Fourier fringe analysis with improved spatial resolution.
AB  - The spatial resolution of the phase image derived from the interferogram by
      Fourier fringe analysis is limited by the necessity to isolate a first order in
      the Fourier plane. By use of the two complementary outputs of the interferometer,
      it is possible to eliminate the zero order and thus to improve the spatial
      resolution by a factor of approximately 2. The theory of this improvement is
      presented and confirmed experimentally.

PMID- 14661793
TI  - Design and assessment of microlenslet-array relay optics.
AB  - Recent progress in micro-optics fabrication and optical modeling software opens
      the opportunity to investigate how microlenslet-array-based compact relay systems
      can be designed and assessed. We present various optical configurations that
      include an appropriate baffle computation to eliminate ghost images, followed by
      an analysis of image quality. The investigation shows the existing trade-off
      between compactness of the system and a tiling effect observed in the
      corresponding image, an effect we refer to as lensletization. To yield meaningful
      optical modeling results, we provide insight into ray-tracing optimization while
      ensuring a sufficient signal-to-noise ratio. The results show that, given no
      discernable lensletization, the most compact configuration to image gray-scale
      images is the 5f-based system. Finally, simulations of the imaging of gray scale
      and color bitmaps through microlenslet arrays are demonstrated for the first time
      to our knowledge.

PMID- 14661794
TI  - Phase recovery from a single undersampled interferogram.
AB  - A new method of phase determination from a single undersampled interferogram is
      described. Two low-fringe-density synthetic interferograms corresponding to the
      phase differences along orthogonal directions are obtained from neighboring
      pixels of the aliased measured data. The only assumption is that the illumination
      background, the modulation intensity, and the searched phase are smooth and
      continuous functions. The synthetic interferograms are demodulated by use of
      either standard frequency or spatial-domain procedures to obtain the phase
      differences. The phase is then recovered by integration of the phase differences
      with a least-squares method. The proposed method is demonstrated to be noise
      tolerant.

PMID- 14661795
TI  - Measurement of profiles along a circle on two flat surfaces by use of a Fizeau
      interferometer with no standard.
AB  - A method for measuring profiles along a circle on a flat surface with no standard
      is described. For the measurement, two unknown surfaces are placed almost
      parallel, and the distance between them is measured many times along a circle by
      rotation of one of the surfaces. Profiles of the two surfaces can be determined
      from the distance data. In this study the measuring method is explained: The
      space between two surfaces measured with a Fizeau interferometer. Four measuring
      experiments are carried out for determining the profile of a precision-grade half
      mirror; in each experiment a different ordinary mirror with unknown profile is
      used as the second mirror. Profiles of the precise mirrors obtained by these
      experiments agree closely, with deviations of approximately 2 nm. A similar
      experiment with many concentric circles was carried out with a precise half
      mirror and another precise mirror. Although the profiles of many concentric
      circles were independent of one another, the result shows that the high-frequency
      component of a whole plane can be estimated.

PMID- 14661796
TI  - High-resolution two-dimensional angle measurement technique based on fringe
      analysis.
AB  - A novel angle-measurement technique based on fringe analysis for phase-measuring
      profilometry is proposed. A two-dimensional (2-D) angle between two mirror
      surfaces is determined by least-squares fitting of a plane to the 2-D
      distribution of the phase difference introduced by the 2-D tilt angle. To
      evaluate the performance of the proposed technique, numerical simulations that
      use the Fourier-transform technique and the phase-shift technique for fringe
      analysis were performed, and the results are compared. A 2-D angle-measurement
      interferometer based on a Mirau interference microscope was developed that
      demonstrated the validity of the proposed principle. It is shown by simulation
      and experiment that the proposed 2-D angle-measurement technique can achieve both
      a wide measurement range and a high angular resolution simultaneously.

PMID- 14661797
TI  - Measurement of air turbulence for on-machine interferometry.
AB  - There is increasing demand for in situ shape measurements performed on
      ultraprecision processing machines. One major source of error during
      interferometric measurements performed on machines is fringe displacement due to
      external disturbances. We have developed an interferometer equipped with an
      electro-optic phase modulator that measures the phase of interference fringes
      before they are displaced by air turbulence. The frequency characteristics of air
      turbulence induced by a heat source are derived from successive measurements of a
      test surface. Experimental results show that the phase of the interference
      fringes can be accurately measured in the presence of air turbulence when the
      intensity of the fringes is sampled at a speed of several hundred hertz.

PMID- 14661798
TI  - Development in situ for gratings recorded in photoresist.
AB  - A technique for developing recording gratings in situ in Photoresist Shipley S
      1822 is described. The developing process is accomplished by use of a spray
      without removing the sample from the optical setup. The results for the
      diffraction efficiency show that there is not a large difference between gratings
      achieved with the traditional wet development process and those obtained with the
      in situ developing technique. The potential of this in situ developing technique
      is shown with a moire interferometric experimental setup used for displacement
      showing.

PMID- 14661799
TI  - Interference effect in apertureless near-field fluorescence imaging.
AB  - Apertureless scanning near-field optical microscopy has been used to image
      fluorescent latex spheres with a resolution of a few tens of nanometers and good
      signal-to-noise ratio. The near-field fluorescence images reveal optical
      interference with several highly contrasted fringes located around the spheres.
      The origin of the interference is discussed in detail, and models are used to
      explain their formation. Spatial coherence is also discussed.

PMID- 14661800
TI  - Micro-optical 1 x 4 fiber switch for multimode fibers with 600-microm core
      diameters.
AB  - The design, manufacture, and test of a 1 x 4 micro-optical fiber switch for
      multimode fibers with 600-microm core diameters are described. Microlens array
      telescopes allow for variable and fast beam deflection when the positions of the
      cylindrical microlens arrays relative to each another are altered by specially
      designed piezomechanical actuators. Standard achromats are used for collimation
      of light emitted by the input multimode fiber and for focusing of the deflected
      light onto a linear array of output multimode fibers. Design and assembly of
      micro-optical as well as of optomechanical components are discussed. Insertion
      loss and cross talk are measured, and the results are compared with those of
      numerical optical simulations. Measurements of switching time and long-term
      stability, as well as of thermal behavior, are also presented.

PMID- 14661801
TI  - Wavelength and temperature performance of polarization-transforming fiber.
AB  - We have theoretically and experimentally investigated an optical fiber with
      circular polarization modes on one end and linear polarization modes on the other
      end. We call this fiber a polarization-transforming fiber because the local
      modes, or polarization states they represent, are converted from linear to
      circular, and visa versa, in the fiber. We have developed and implemented a
      postdraw process for making polarization-transforming fiber samples 30 mm long
      with losses less than 1 dB and a polarization-mode conversion from circular to
      linear greater than 20 dB. Also, we have modeled and measured the dependence on
      wavelength and temperature of polarization-transforming fiber samples. The
      measured normalized wavelength dependence of a sample fiber 30 mm long was
      approximately 1.4 x 10(-4) nm(-1), and the measured normalized temperature
      dependence was approximately 6 x 10(-4) degrees C(-1). These values are better in
      some cases than values for conventional high-birefringent fiber quarter-wave
      plates.

PMID- 14661802
TI  - Silicon-based surface plasmon resonance sensing with two surface plasmon
      polariton modes.
AB  - Surface plasmon resonance (SPR) sensing on a silicon-based platform is
      considered. We have studied properties of SPR in a combined silicon-dielectric
      layer-gold film-sample medium structure and established conditions of the
      simultaneous excitation of two plasmon polariton modes that provide narrow and
      well-separated minima of the reflected intensity. It has been shown that the
      external mode over the gold-sample medium interface demonstrates a highly
      sensitive response to a change in the refractive index of the sample medium,
      whereas the internal mode over the dielectric-gold interface is almost
      insensitive to medium parameters. We propose that the internal mode can be used
      as an effective reference zero point for miniature and portable SPR-based systems
      designed for field and multichannel sensing.

PMID- 14661803
TI  - Analytic expressions for the fourth- and the fifth-order dispersions of crossed
      prisms pairs.
AB  - In case of tunable ultrashort-pulse lasers, besides the prism material,
      separation, and insertion, one may choose the central wavelength providing a
      better high-order dispersion compensation. Because of errors that accumulate in
      numerical iterations, the analytic approach may be preferable for high-order
      dispersion examination. Analytic expressions for the fourth- and the fifth-order
      dispersions of crossed prisms pairs, both at arbitrary and Brewster-angle
      incidences are presented. Examples are given for e-sapphire slabs and for one or
      two pairs of fused-silica prisms. Results are shown providing compensation of
      both the second- and the third-order dispersions, by keeping as low as possible
      the higher-order ones.

PMID- 14661804
TI  - Method for determination of the dielectric function of a thin absorbing film on
      variable substrates from transmission spectra.
AB  - Transmission spectra of bilayers of a strongly absorbing dye molecule on thin
      semitransparent metallic films show a pronounced variation of the shape as a
      function of the thickness of the metal film. The shape changes with increasing
      thickness of the metal film from the form of an absorption spectrum as determined
      by the imaginary part of the dielectric function to an antisymmetric shape
      characteristic of the dispersion of the real part of the dielectric function in
      the vicinity of a resonance. These different spectra shapes were exploited to
      derive the complex dielectric function of a dye layer from transmission spectra
      of the layer on metal films of a different thickness. This method proved to be a
      simple alternative to determination of the dielectric function of a thin film of
      a dye by spectroscopic ellipsometry.

PMID- 14661805
TI  - Thin-film achromatic phase shifters for nulling interferometry: design approach.
AB  - Nulling interferometry in the thermal IR is the most promising technique for
      direct detection of Earth-like exoplanets. This technique requires a pi phase
      shifter for the parent star of the planet to be completely extinguished by
      destructive interference. We investigate how thin films can be used to design pi
      achromatic phase shifters. The design approach that we propose works on
      reflection and can be carried out by two steps, namely, the design of a mirror
      and an antireflection structure with no constraint on the phase properties of the
      thin film stacks. Phase-shift accuracy is derived analytically, and a numerical
      example illustrates this concept.

PMID- 14661806
TI  - Thermal-changeable complex-refractive-index spectra of merocyanine aggregate
      films.
AB  - Thermal behaviors of complex refractive index of merocyanine (MC) Langmuir
      Blodgett (LB) films have been investigated with absorption spectrum measurements,
      which are obtained from the Kramers-Kronig (K-K) analysis. The complex-refractive
      index spectra with an anomalous dispersion around a J-aggregate absorption band
      of MC molecules are changed by annealing temperatures. This thermal
      characteristic is attributed to the annealing-changeable MC J-aggregates. The MC
      J-aggregates in the LB films collapse in the annealing and become a monomer
      state. The refractive-index dispersion decreased with the collapse of MC J
      aggregates. These behaviors are confirmed from the reflection spectrum
      measurements under the different conditions of incident light to the MC film
      samples.

PMID- 14661807
TI  - Highly efficient transmission gratings in fused silica for chirped-pulse
      amplification systems.
AB  - We report on highly efficient transmission gratings in fused silica with a
      grating period of 800 nm generated by electron-beam lithography. At a wavelength
      of 1060 nm, 95% diffraction efficiency is achieved under Littrow conditions. The
      damage threshold, extremely enhanced compared with conventional gold-coated
      diffraction gratings, makes these gratings the key elements in high average power
      (>100 W) femtosecond fiber chirped-pulse amplification systems.

PMID- 14661808
TI  - Effect of tin diffusion on the optical behavior of float glass in the soft-x-ray
      region.
AB  - The optical responses of two sides of float glass in the soft-x-ray region were
      studied at the Indus-1 synchrotron facility. To the best of our knowledge these
      are the first experimentally obtained optical data for both sides of float glass
      in the soft-x-ray region. Optical constants delta and beta were determined by use
      of angle-dependent reflectance techniques in the wavelength range 80-200 A. On
      the side of the glass that was tin indiffused, a significant difference in delta
      value from that of the non-tin-side surface was observed. The measured data were
      compared with Henke's tabulated value of SiO2. The surface roughness of float
      glass was separately determined by hard-x-ray reflectivity to minimize the number
      of fitting variables. The effect of a contamination layer on the determination of
      optical constants was avoided by an appropriate sample-cleaning method.

PMID- 14661809
TI  - Production and performance of multilayer-coated conical x-ray mirrors.
AB  - A method of fabricating replica figured x-ray optics with integral multilayer
      coatings is presented. With the intact electroforming multilayer process (IEMP)
      technique, we sputter multilayers onto a reusable superpolished mandrel,
      electroform nickel over the multilayers, and remove the multilayer-coated nickel
      shell intact from the mandrel. This approach offers advantages over more
      traditional, original, and segmented-replica fabrication techniques, including
      low cost; compatibility with a wide range of mirror designs, diameters, and focal
      lengths; simple integration with multilayer sputtering processes; and the ability
      to produce complete shells of revolution. The fabrication of W/Si multilayer
      coated 10-cm-diameter conical x-ray mirrors is described, as are reflectivity
      measurements at 10 and 30 keV. The measured reflectivity of the IEMP multilayers
      at the 10-keV primary Bragg peak was 17%. Measurements of multiple points on the
      cone showed multilayer uniformity to within a few percent around the mirror.

PMID- 14661810
TI  - Common-path interferometer for frequency-domain optical coherence tomography.
AB  - A Michelson-type spectral interferometer that uses a common beam path for the
      reference and the sample arms is described. This optical arrangement is more
      compact and stable than the more commonly used dual-arm interferometer and is
      well suited for frequency-domain optical coherence tomography of biological
      samples. With a 16-bit CCD camera, the instrument has sufficient dynamic range
      and resolution for imaging to depths of 2 mm in scattering biological materials.
      Images obtained with this spectral interferometer are presented, including cross
      sectional images in a Xenopus laevis tadpole.

PMID- 14661811
TI  - Phase-slope and group-dispersion calculations in the frequency domain by simple
      optical low-coherence reflectometry.
AB  - We report a new method by which phase slope and group dispersion can be
      calculated with a simple optical low-coherence reflectometer to quantify
      physiological conditions. A discrete-time signal processing algorithm based on
      the first and second derivatives of the phase with respect to wave number was
      developed from discrete-time Fourier properties. The algorithm avoids the 2pi
      ambiguity associated with most phase unwrapping. Experimental data collected by
      use of well-characterized optical materials validated the algorithm, which was
      minimally sensitive to phase noise. The group dispersion of bovine cornea was
      measured at various hydrations and was significantly dependent on hydration. The
      results suggest that group dispersion is an indicator of corneal alterations.

PMID- 14661812
TI  - Age identification in the framework of successful aging. A study of older Finnish
      people.
AB  - A person-oriented approach was used in a study of age identification among
      community-dwelling older people. The study was based on 8-year follow-up data;
      843 persons aged 65-84 were involved in the first phase of the study, and 426
      persons aged 73-92, in the second phase. Loosely, on the basis of the distinction
      between successful, usual, and pathological aging (Rowe & Kahn, 1987, 1997),
      participants were grouped according to their self-ratings of cognitive and
      physical functioning as "Positive," "Negative," and "Others." Participants
      possessing at least 4 out of the 5 criteria used as indicators of successful
      aging in the study (no illness or injury presenting problems in daily life, no
      health problems imposing limitations on hobbies, self-rated cognitive functioning
      better than satisfactory, age-comparative functional capacity as good, and no
      signs of depression) were assigned to the "Positive" group. The results showed
      these individuals typically to have a more youthful age identity, indicated by a
      lower feel age and thus a lower subjective age-perception score, lower mental,
      physical, and look ages, and a less frequently reported sense of age weighing on
      them. Moreover, this group reported a higher ideal age and had a chronological
      age satisfaction score closer to 0, suggesting higher satisfaction with
      chronological age. Also a tendency to set the onset of old age later and a
      willingness to live to 100 years of age were features that were more
      characteristic of the "Positive" than the other groups. The findings, supported
      by multivariate analyses, were in line with those of previous variable-oriented
      studies on age identification, suggesting that an association exists between
      perceptions of personal aging and physical and psychological well-being.

PMID- 14661813
TI  - Determinants of self-perceived changes in health status among pre- and early
      retirement populations.
AB  - Using data from the 1992 and 1994 waves of the Health and Retirement Study (HRS),
      this study described reasons reported by pre- and early-retirement populations
      for perceived changes in global health status over a 2-year period. It then
      analyzed the association between self-perceptions of change and the actual
      changes in objective health conditions, controlling for demographics, emotional
      health status, and the changes in work status and health-affecting habits. The
      results were compared to the determinants of self-ratings of health at wave 2.
      Existing or increasing impairments in functional abilities were found to
      contribute to self-perceptions of decline. However, a diagnosis of new chronic
      disease and the experience of a major medical event per se did not universally
      contribute to self-perception of decline. The relationship between cross
      sectional self-ratings of health and objective health conditions was more
      straightforward. Self-perception of improvement among people with serious health
      problems most likely owed to medical interventions and improvement in symptoms,
      the most frequently mentioned reasons for perceived improvement, and reflected
      the subjects' selective optimization and resiliency.

PMID- 14661814
TI  - Successful aging: perceptions of adults aged between 70 and 101 years.
AB  - In this research, content analysis was employed to investigate older adults'
      perceptions of successful aging and the relationship of these perceptions to
      definitions given in the literature to date. Participants were 18 males and 42
      females between the ages of 70 and 101 years. Analyses revealed older adults
      mentioned only 1 or 2 criteria of successful aging if asked for a definition;
      however, when prompted, they rated almost all the criteria emerging from the
      literature as highly important. Participants reported adjusting to the situations
      they were in by compensating for losses that occurred and selecting activities
      that best suited their capabilities. Overall, older adults' perceptions of
      successful aging were similar to aspects identified in the literature. Not all
      aspects, however, were seen as important by all participants, and only low to
      moderate correlations were found between some aspects of successful aging.

PMID- 14661815
TI  - Stability and change in positive self-appraisal from midlife to later aging.
AB  - This research investigated stability and change in the self-appraisal of having
      lived up to one's abilities from midlife to later aging. The subjects were 185
      participants in the Terman Study of the Gifted, who had been asked to rate
      themselves with respect to living up to their abilities in 1960 (at an average
      age of 48) and in 1996 (at an average age of nearly 85). While there was a
      positive relation between self-appraisal at the 2 times, net change favored a
      more positive appraisal in aging. Those who rated themselves positively at both
      times had more positive personality characteristics in early to mid-adulthood,
      more education, better self-rated health in midlife, somewhat higher ambition in
      early adulthood and midlife, and greater satisfaction with their achievement in
      early aging. Those who changed positively in their self-appraisal, as compared
      with those with a negative later self-appraisal, had somewhat better education,
      better self-rated health in midlife, higher level occupations, and greater
      satisfaction with their achievement in early aging. Self-appraisals in later
      aging were related to current life satisfaction. The results are discussed in
      terms of the role of the self-concept and the self-narrative in life-span
      development.

PMID- 14661816
TI  - Injectable bisphosphonates in the treatment of postmenopausal osteoporosis.
AB  - Osteoporosis is a "silent" disease and the patient has usually no clue of it
      until the occurrence of a fragility fracture. Prevention requires a continuous
      daily treatment that could be uncomfortable to the patient. Besides the recently
      introduced weekly oral schedules, injectable bisphosphonates have often been used
      as an off-label option to ameliorate compliance. In general, although with
      different efficiency, almost all injectable bisphosphonates can improve bone
      mineral density and suppress bone resorption markers. The effect of intravenous
      infusions of bisphosphonates are, to a large extent, similar to equivalent
      intramuscular administrations, but doses and dosing intervals represent the
      critical issues. Pain at the injection site and acute phase reactions are
      relatively common to intramuscular clodronate and intravenous infusions of
      nitrogen-containing bisphosphonates, respectively. Under certain circumstances,
      intermittent treatment with injectable bisphosphonates might represent a feasible
      alternative when compliance is at risk.

PMID- 14661817
TI  - ACE genotype and physical training effects: a randomized study among elderly
      Danes.
AB  - BACKGROUND AND AIMS: The level of physical functioning (PF) late in life has, in
      recent years, been shown to be influenced by genetic factors. One of the most
      extensively studied genetic variants associated with PF and trainability is
      insertion/deletion (I/D) polymorphism in the gene encoding Angiotensin Converting
      Enzyme (ACE). However, ACE studies have mainly been conducted among younger
      persons in excellent physical shape. In this study, we examine whether the level
      of PF, trainability, or rate-of-change are associated with the ACE genotype among
      the elderly. METHODS: We used data from 4 randomized training studies of elderly
      Danes (N = 203). The measures of PF were self-report, maximal oxygen uptake,
      muscle strength, walking speed, and body composition. RESULTS: Overall, a
      favorable change in the measures of PF was observed in training groups compared
      with control groups. However, within groups, neither pre- or post
      training/control period levels of PF nor differences in pre- and post-levels were
      associated with the ACE genotype. CONCLUSIONS: On the basis of our randomized
      studies, we could not detect any association between the ACE genotype and the
      level of PF or change, regardless of whether response to physical training or
      spontaneous changes was studied.

PMID- 14661818
TI  - Allele frequencies of +874T --> A single nucleotide polymorphism at the first
      intron of IFN-gamma gene in Alzheimer's disease patients.
AB  - BACKGROUND AND AIMS: Inflammation seems to play a role in progressive
      neurological degenerative diseases such as Alzheimer's disease (AD). Local
      inflammatory processes can in fact give rise to direct neurotoxicity, interfere
      with beta-amyloid expression and metabolism, and maintain chronic, intracerebral,
      acute-phase protein secretion, in turn favoring the formation of beta-amyloid
      fibrils. Accordingly, recent studies show an increased risk for AD associated
      with certain polymorphisms in the genes encoding some proinflammatory cytokines
      and acute-phase proteins. To our knowledge, no data have yet been presented on
      the association between AD and polymorphisms of the interferon(IFN)-gamma gene,
      despite the pivotal role that IFN-gamma plays in immune-mediated inflammatory
      responses. METHODS: Using the amplification refractory mutation system method, we
      evaluated the role of IFN-gamma in AD by analyzing, in 111 AD patients and 213
      healthy controls, the prevalence of +874T --> A single nucleotide polymorphism
      (SNP), associated with different IFN-gamma production. Allele ApoE polymorphisms
      were assessed by the PCR-based method. RESULTS: No statistically significant
      differences were observed between AD patients and controls in the frequency of
      +874T --> A SNP, either on analyzing data as a whole or according to gender. As
      expected, the frequency of the well-known genetic risk factor APOE-epsilon4
      allele was significantly increased in AD patients. However, analyzing the results
      according to the presence or absence of the APOE-epsilon4 allele, no interactions
      among ApoE, IFN-gamma alleles, gender or age at onset were observed. CONCLUSIONS:
      Our study does not support the hypothesis that IFN-gamma SNP may be a genetic
      risk factor for AD. Further analysis of recently described IFN-gamma
      polymorphisms may clarify the role, if any, of IFN-gamma alleles in AD.

PMID- 14661819
TI  - Seasonal hypertension: a clue to explain the high prevalence of unrecognized
      hypertension in the elderly? Gruppo Italiano di Farmacovigilanza nell'Anziano
      (GIFA).
AB  - BACKGROUND AND AIMS: Blood pressure is known to be influenced by the season,
      particularly in the elderly. The association between cold weather and
      unrecognized hypertension has not been previously studied. The present study
      aimed at assessing whether recognition of hypertension in the elderly follows a
      seasonal pattern. METHODS: All patients over 64 with either first-listed or
      secondary diagnosis of hypertension at discharge (N = 4487) out of 24585
      consecutively admitted to 69 wards of Geriatrics or Internal Medicine during ten
      bi-monthly observation periods (May-June and September-October) were enrolled.
      The main outcome of the study was the prevalence of unrecognized hypertension,
      defined as no mention of hypertension and/or antihypertensive drugs in clinical
      histories collected on admission, and a first-listed or secondary discharge
      diagnosis of hypertension. RESULTS: We found a total of 928 patients with
      unrecognized hypertension. Being admitted in the September-October period was
      independently associated with the outcome unrecognized hypertension (OR 1.25, 95%
      CI 1.08-1.46), as were smoking addiction (OR 1.57, 95% CI 1.23-2.0) and
      allocation to a medical ward (OR 1.21, 95% CI 1.04-1.41). Negative correlates of
      the outcome were multiple pathologies (OR 0.85, 95% CI 0.73-0.99), discharge
      diagnosis of coronary artery disease (OR 0.77, 95% CI 0.64-0.92) or diabetes
      mellitus (OR 0.81, 95% CI 0.67-0.97). CONCLUSIONS: Hypertension in the elderly
      may at least partly follow a seasonal pattern, and this finding may be relevant
      for screening and therapeutic decisions.

PMID- 14661820
TI  - Hydration status of community-dwelling seniors.
AB  - BACKGROUND AND AIMS: Dehydration is the most common fluid or electrolyte disorder
      among older persons. This study was designed to examine the hydration status of
      community-dwelling seniors. METHODS: Blood and urine samples were collected from
      67 independently living volunteers (65-93 yrs) who had functional limitations but
      no condition that contraindicated 10 min of moderate exercise. Forty-six subjects
      who were not diabetic, had fasted for 12 hours, and had blood glucose levels < or
      = 115 mg/dL were thus included. Urine and serum samples were analyzed for
      osmolality (mosm/kg), Na+ (mmol/L) and K+ (mmol/L). Whole blood was analyzed for
      hemoglobin (Hb, g/dL) and hematocrit (Hct, %) and urine for specific gravity
      (USG). Means and standard deviations for the current data were compared with
      normal values. RESULTS: All values were within normal ranges except urine
      osmolality. CONCLUSIONS: While changes associated with aging may predispose an
      individual to dehydration, functionally limited, independently living older
      individuals demonstrate normal hydration status following a 12-hr fast. This
      suggests that dehydration is not solely a function of the aging process, but may
      be more related to concomitant medical conditions or dependent living.

PMID- 14661821
TI  - Multidimensional assessment and risk factors for prolonged hospitalization in the
      elderly.
AB  - BACKGROUND AND AIMS: Frailty, multiple pathologies, functional impairment and
      socioeconomic conditions can prolong the length of hospitalization in the
      elderly. The aim of our study was to analyze risk factors for prolonged
      hospitalization. METHODS: Our sample included 1054 patients consecutively
      admitted to the University Department of Geriatric Medicine of Torino, Italy. We
      examined some demographic variables (age, sex, socioeconomic conditions),
      affective, cognitive and functional status, main pathologies, and blood pressure
      and some hematological parameters (hemoglobin, creatinine, albumin, sodium).
      RESULTS: The number of functions lost to IADL and ADL, DMI (Dependent Medical
      Index) dependence, high levels of creatinine and low blood levels of albumin and
      sodium were associated with longer hospitalization, as also were the following
      clinical diagnoses: tumor, chronic obstructive pulmonary disease (COPD), hip
      fractures, peripheral arterial disease (PAD), and pressure sores. Independent
      predictors of prolonged hospitalization were: the number of functions lost to the
      ADL index, pressure sores, hip fracture, peripheral arterial disease with
      critical ischemia, and low levels of sodium. CONCLUSIONS: Multidimensional
      assessment is essential to identify medical, functional and socioeconomic
      problems, and can highlight risk factors for prolonged hospitalization.

PMID- 14661822
TI  - Sex-related differences in the length of disability prior to death in older
      persons.
AB  - BACKGROUND AND AIMS: It is acknowledged that, in spite of their generally worse
      health, women live longer than men. However, whether women also enjoy longer
      disability-free lives is still unclear. Using data from a representative, Italian
      cohort followed for 6 years, this study aimed at estimating differences between
      men and women in the age of disability onset and in total survival. METHODS: In
      1989, 651 persons aged > or = 65 years were interviewed and their medical status
      was assessed by a geriatrician. In 1995, the time of onset of disability was
      reconstructed by re-interviewing 392 survivors and collecting proxy information
      for 201 subjects who had died. No information was available for 58 subjects who
      refused to be re-interviewed or were lost to follow-up. Data on changes in
      functional status were also collected by proxy interview for 34 additional
      persons who had died during the follow-up period, although they had not been
      originally interviewed at baseline. RESULTS: Of the 235 deaths, 113 were men and
      122 were women. On average, the age at death was 3.5 years higher among women
      than among men. However, the age at onset of disability was similar in the two
      sexes. In survival analysis in which age was the time variable, women were as
      likely as men to develop disability, but significantly less likely to die over
      the follow-up period. CONCLUSIONS: Compared with men, women experience longer
      disability before death. This may be due to sex-related differences in the
      lifetime prevalence of lethal vs. disabling diseases.

PMID- 14661823
TI  - Predictors of recovery in activities of daily living among disabled older Mexican
      Americans.
AB  - BACKGROUND AND AIMS: Although functional ability decreases with age and is
      associated with poor health outcomes, decline in functional ability is
      reversible. The aim of this study is to describe the rate of recovery of
      functional ability and to identify factors associated with it over a two-year
      period among older Mexican Americans. METHODS: 245 functionally disabled older
      Mexican Americans were included in a two-year prospective cohort study. Data are
      from the Hispanic Established Population for the Epidemiological Study of the
      Elderly (H-EPESE), a population-based study of non-institutionalized Mexican
      Americans in the South-western United States. Activities of daily living (ADL),
      lower body mobility (tandem balance, eight-foot walk, and repeated chair stands),
      depressive symptomatology, body mass index, and self-reported medical conditions
      were obtained. RESULTS: Over a two-year period, of the 245 subjects at baseline
      who reported functional disability in at least 1 of 7 ADLs, 83 totally recovered
      their ADL ability, 108 remained disabled, 36 died, and 18 were lost to follow-up.
      Factors significantly associated with recovery included younger age (65-74) (OR
      2.18, 95% CI 1.08-4.42), higher summary performance measure of lower body
      function (OR 1.19, 95% CI 1.05-1.34), few depressive symptoms (OR 2.84, 95% CI
      1.39-5.78), and a BMI > or = 30 Kg/m2 (OR 3.08, 95% CI 1.17-8.07). Higher numbers
      of ADL limitations at baseline were associated with lower odds of ADL recovery.
      CONCLUSIONS: Two-year recovery from ADL disability among older Mexican Americans
      was high (33.9%). Factors independently associated with recovery include younger
      age, few depressive symptoms, good lower body function, and high BMI.

PMID- 14661824
TI  - Body composition changes in stable-weight elderly subjects: the effect of sex.
AB  - BACKGROUND AND AIMS: Although cross-sectional and longitudinal studies have shown
      age-related changes in body composition and fat distribution, they may be related
      to body weight changes. The aim of this study was to evaluate yearly age-related
      changes in body composition and fat distribution, over a two-year period, in 101
      women and 60 men (age range: 68 to 78 years at baseline). METHODS: Body
      composition was evaluated by dual energy X-ray absorptiometry (DXA), and fat
      distribution by waist and hip circumferences and waist-to-hip circumference
      ratio. Baseline free testosterone, IGF-1 and serum albumin were evaluated in all
      subjects, as well as physical activity. Clinical evaluation was performed at
      baseline and yearly in order to exclude subjects with any condition inducing
      pathological changes in body composition or fat distribution. Subjects with a
      weight change > 5% of their baseline body weight during the study period, were
      excluded. RESULTS: Significant increases occurred in Body Mass Index (BMI) (1.18%
      in women, 1.13% in men), waist (1.75% in women, 1.39% in men), and hip
      circumference (1.06% in women, 1.31% in men), whereas height decreased
      significantly in both men (0.42%) and women (0.55%). Significant increases in
      total body fat (1.31%) and percent body fat (1.27%) were observed in women but
      not in men. Lean body mass did not change significantly throughout the study in
      either sex. Significant losses in leg muscle mass and appendicular skeletal
      muscle mass (ASM), calculated as the sum of arm and leg fat-free soft tissue,
      were observed in men (respectively 3.56 and 2.77%) and women (respectively 2.41
      and 1.59%). A significant decrease in ASM adjusted by stature (ASM/height2), a
      proposed proxy for sarcopenia, was found in men only (1.97%). The rates of loss
      in leg muscle mass and appendicular muscle mass were significantly higher in men
      than in women, even after adjusting for free testosterone, IGF-1, physical
      activity and serum albumin. CONCLUSIONS: These data demonstrate significant
      changes in body composition and fat distribution in independently living, weight
      stable elderly men and women. These changes are dependent on sex and independent
      of physical activity, hormones or serum albumin.

PMID- 14661825
TI  - Predicting mortality in older patients. The VELCA Study.
AB  - BACKGROUND AND AIMS: Mortality at older age, during and after hospitalization,
      can be determined by several factors, beyond the direct cause for hospital
      admission, which are not yet fully understood. The aim of this study was to
      assess predictors of inpatient mortality and one-year mortality in older
      Italians, hospitalized for dementia, heart failure, chronic obstructive pulmonary
      disease, stroke, hip fracture and myocardial infarction at the Verona Teaching
      Hospital, Northern Italy. METHODS: At admission, 429 patients aged 65 years and
      older reported information on: sociodemographic characteristics, Barthel index at
      admission and two weeks before, and severity of investigated diagnosis; at
      discharge: diagnosis, comorbid conditions, complications from hospital records,
      drug therapy, and Barthel index. One year after discharge, an ad hoc
      questionnaire for those subjects found to have died on phone contact was
      administered to a proxy to collect data on new hospital admissions, onset of new
      conditions, need for formal care, a short version of the Barthel index one month
      before death, and the place of death. RESULTS: Sex and specific diseases at
      admission were not significant predictors of inpatients, nor was one-year
      mortality in this cohort, whereas the presence of any comorbid conditions doubled
      the risk of mortality at one year compared with patients without comorbidity.
      Those patients who had moderate to severe/total dependency in ADL at admission
      were three times more likely to have died at discharge than those who were
      independent. The same risk for mortality at one-year follow-up was found in those
      patients who were severely or totally dependent at preadmission, at admission, or
      at discharge. CONCLUSIONS: Functional status and comorbidity are key risk factors
      for mortality in the elderly. Therefore, multidimensional assessment, including
      functional status prior to hospitalization should always be assessed, and should
      be considered a relevant predictor of short- and long-term outcomes.

PMID- 14661826
TI  - Associations with successful ageing in the "Healthy Old People in Edinburgh"
      cohort: being well, fit and healthy.
AB  - BACKGROUND AND AIMS: Six hundred and three community-resident, healthy,
      unmedicated people aged 70 years and over had psychometric testing and blood
      pressure measured in 1990-1. Participants were followed up in 1994-5, 1997-8 and
      in this fourth wave of the project, 1999-2000, to determine key predictors of,
      and associations with successful ageing. METHODS: Current status of all cohort
      participants was determined. Those traced and alive were invited for re
      assessment. Those who agreed underwent psychometric testing, including memory and
      fluid intelligence tests, a number of physiological measurements, including blood
      pressure, grip strength and respiratory function, and questionnaires were
      administered enquiring about disability, self-esteem, and a range of
      socioeconomic and socioenvironmental items. RESULTS: At Wave 4, 201 participants
      were visited and re-tested adequately. During follow-up, mortality (N = 210) was
      predicted by gender, occupation, premorbid intelligence and blood pressure.
      Disability related to age, weight, respiratory function, grip strength and
      current mental ability. A model of health was developed that comprised dimensions
      of medical well-being (absence of disease), physiological fitness and self
      perceived health. The latter related strongly to disability and pre-morbid
      intelligence. Except for memory score at Wave 3, medical well-being related
      poorly to any predictor variable from Waves 1-3. Physiological fitness related to
      age, gender and current mental ability. CONCLUSIONS: The concept of successful
      ageing is complex, but this cohort of older people related their perceived health
      closely to lack of disability. In this cohort, current socioeconomic and
      socioenvironmental factors were not strongly linked with health at this age.

PMID- 14661827
TI  - Diffuse idiopathic skeletal hyperostosis: an uncommon case of dysphagia in an
      older adult.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is a common disorder among older
      adults. It is characterized by ossification of the anterior longitudinal ligament
      of the spine and various extra-spinal ligaments. Although stiffness and decreased
      range of motion of the spine are the most common clinical presentations of DISH,
      extra-skeletal manifestations may also be present. We report the case of a 65
      year-old man complaining of progressive dysphagia due to DISH. Barium swallow
      showed compression and lateral displacement of the cervical tract of the
      esophagus, secondary to compression by a large osteophyte. The patient received
      medical treatment with COX-2 inhibitors and liquid diet. In conclusion, DISH
      should be considered an important, although rare, cause of dysphagia among older
      adults. However, it should not be accepted as the cause of dysphagia until all
      other causes have been ruled out.

PMID- 14661828
TI  - Geriatric medicine in the European Union: unification of diversity.
AB  - The numbers of older people in the European Union are increasing and, with their
      associated health needs, there is a requirement for the specialty of Geriatric
      Medicine to be available throughout Europe. At present, specialists in Geriatric
      Medicine are not recognised in some of the European Union member countries. It is
      imperative that training in Geriatric Medicine should take place throughout
      Europe, starting at undergraduate level and progressing through postgraduate
      training. There must be a programme of continuing medical education and personal
      development. This paper highlights some of these challenges and suggests a
      possible way forward.

PMID- 14661829
TI  - Cooperative effort between local health services, doctors and the elderly
      population to reduce bone densitometry waiting lists.

PMID- 14661830
TI  - Identification of bacterial spores using statistical analysis of Fourier
      transform infrared photoacoustic spectroscopy data.
AB  - Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) has been applied
      for the first time to the identification and speciation of bacterial spores. A
      total of forty specimens representing five strains of Bacillus spores (Bacillus
      subtilis ATCC 49760, Bacillus atrophaeus ATCC 49337, Bacillus subtilis 6051,
      Bacillus thuringiensis subsp. kurstaki, and Bacillus globigii Dugway) were
      analyzed. Spores were deposited, with minimal preparation, into the photoacoustic
      sample cup and their spectra recorded. Principal component analysis (PCA),
      classification and regression trees (CART), and Mahalanobis distance calculations
      were used on this spectral library to develop algorithms for step-wise
      classification at three levels: (1) bacterial/nonbacterial, (2) membership within
      the spore library, and (3) bacterial strain. Internal cross-validation studies on
      library spectra yielded classification success rates of 87% or better at each of
      these three levels. Analysis of fifteen blind samples, which included five
      samples of spores already in the spectral library, two samples of closely related
      Bacillus globigii 01 spores not in the library, and eight samples of nonbacterial
      materials, yielded 100% accuracy in distinguishing among bacterial/nonbacterial
      samples, membership in the library, and bacterial strains within the library.

PMID- 14661831
TI  - External cavity diode laser based photoacoustic detection of CO2 at 1.43 microm:
      the effect of molecular relaxation.
AB  - Photoacoustic spectroscopy, based on an external cavity diode laser operating at
      1431 nm, was used for measuring CO2 concentration as a minority component in a
      gas mixture. By using N2 as a buffer gas, a molecular relaxation effect was
      observed, which influenced both the amplitude and the phase of the measured
      photoacoustic signal and consequently reduced the sensitivity of the PA system.
      This molecular relaxation effect could be suppressed by adding water vapor of a
      constant and relatively high (approximately 4%) concentration to the gas sample.
      In parallel with this, the arising spectral interference between H2O and CO2
      necessitated the development of a simple yet efficient signal analysis method,
      which increased the sensitivity of the system by more than one order of magnitude
      and accordingly reduced the minimum detectable CO2 concentration down to
      approximately 1000 ppm.

PMID- 14661832
TI  - Gas-phase detection of trinitrotoluene utilizing a solid-phase antibody
      immobilized on a gold film by means of surface plasmon resonance spectroscopy.
AB  - A multilayered biosensor was constructed and found to detect trinitrotoluene
      (TNT) in ppb concentrations in air both prior to and after detonation of TNT
      without use of a liquid phosphate buffered saline (PBS) superstrate. The
      biosensor surface was fabricated from a monoclonal antibody for TNT covalently
      bound to an 11,11'-dithio-bis(succinimidoylundecanoate) (DSU) self-assembled
      monolayer immobilized on a thin gold film bonded to a BK7 glass slide. The
      binding between the immobilized antibody and TNT antigen was detected using
      surface plasmon resonance spectroscopy (SPRS). Biosensor specificity for TNT was
      demonstrated with chemical homologues as well as against an unrelated explosive,
      RDX.

PMID- 14661833
TI  - Reflectometric study of contaminant layer on a probe window.
AB  - In this study properties of a contaminant material on the surface of a probe
      window (prism) were investigated. The probe window, i.e., the prism, is part of
      the reflectometer apparatus exploited in this study. The contaminant layer was
      considered to originate from a pulping solution containing lignin contacting the
      surface of the prism. In these experiments the contact time was up to 5.0 hours.
      To find the values of the contaminant material properties, i.e., refractive index
      (n), extinction coefficient (k), and effective thickness (d), an optical model
      was proposed assuming that the contaminant layer is continuous and homogenous. In
      addition, the model includes an inter-diffusion layer existing between the
      contaminant layer and the lignin solution. From the fitting procedure using the
      optical model of depth profiling, it was found that the growth rate of the
      contaminant layer was approximately 60 nm per hour. The results obtained by
      theory and experiments were consistent for both s- and p-polarizations and for
      the various wavelengths of the light source (300, 400, and 500 nm).

PMID- 14661834
TI  - True chemical composition profiles at polymer interphases: recovery from
      measurements distorted by instrumental broadening.
AB  - The determination of chemical composition profiles at polymer interphases is an
      important issue at the moment of elucidating the physical mechanisms that operate
      in polymer diffusion processes and for calculating diffusion parameters. Several
      techniques are available to measure these profiles, the most common being forward
      recoil spectroscopy, Rutherford backscattering spectrometry, nuclear reaction
      analysis, confocal Raman microspectroscopy (CRM), and scanning infrared
      microscopy. However, all these techniques are affected by the limited resolution
      of the experimental setup, which in practice produces a rounding effect on the
      sharp corners of the composition profile; this may lead to incorrect conclusions
      regarding the measurements. In this work an inverse technique is proposed to
      correct this undesirable effect in the profiles. The inversion is performed on a
      model of the measuring process, which includes the instrumental broadening
      function, a quantitative representation of the limited resolution. The proposed
      methodology was tested using numerically generated experiments and genuine
      experimental runs obtained from CRM measurements at interphases of polymer
      bilayers. In all cases, the recovered profiles were close to the expected ones.
      In the truly experimental results diffusion tails are observed behind and ahead
      of the diffusion front before the numerical treatment of the data. These tails
      may be caused by a genuine mass diffusion or by an artifact. After the numerical
      treatment the tails disappear and a sharp interphase is recovered, a result one
      expects for the polymer pairs under study.

PMID- 14661835
TI  - Quantitative analysis of polyethylene blends by Fourier transform infrared
      spectroscopy.
AB  - The quantitative analysis of binary polyethylene (PE) blends by Fourier transform
      infrared (FT-IR) spectroscopy has been achieved based on the ratio of two
      absorbance peaks in an FT-IR spectrum. The frequencies for the absorbance ratio
      are selected based on structural entities of the PE components in the blend. A
      linear relationship between the absorbance ratio and the blend composition was
      found to exist if one of the absorbance peaks is distinct to one of the
      components and the other peak is common to both components. It was also found
      that any peak resulting from short-chain branching in copolymers (such as linear
      low-density polyethylene (LLDPE) or metallocene-catalyzed LLDPE (mLLDPE)), is
      suitable for use as the peak that is designated as being distinct to that
      component. In order to optimize the linearity of the equation, however, the
      selection of the second common peak is the most important and depends on the
      blend system studied. Indeed, under certain circumstances peaks that are not
      spectrally distinct can be used successfully to apply the method. The method
      exhibits potential for the routine analysis of PE blends that have been
      calibrated prior to its application.

PMID- 14661836
TI  - Two-dimensional infrared spectroscopy and principal component analysis studies on
      a new azobenzene derivative supramolecular system based on hydrogen bonds.
AB  - Infrared (IR) spectra of a supramolecular assembly with an azobenzene derivative
      and intermolecular hydrogen bonds have been measured in the temperature range
      from 30 to 200 degrees C to investigate heat-induced structural changes and
      thermal stability. Principal component analysis (PCA) and two kinds of two
      dimensional (2D) correlation spectroscopy, variable-variable (VV) 2D and sample
      sample (SS) 2D spectroscopy, have been employed to analyze the observed
      temperature-dependent spectral variations. The PCA and SS 2D correlation analyses
      have demonstrated that the complete decoupling of hydrogen bonds in the
      supramolecular assembly occurs between 110 and 115 degrees C, which is in good
      agreement with the results of a differential scanning calorimetry (DSC) study for
      the heating process. The PCA of the IR spectra in the region of 3600-3100 cm(-1)
      has illustrated that there are at least four principal components for the
      different NH2 and CONH species in the present supramolecular system. The VV 2D
      correlation spectroscopy study has provided information about the structure and
      strength of hydrogen bonds of NH2 and CONH groups and their temperature-dependent
      variations. The different species of hydrogen-bonded NH2 and CONH groups in the
      supramolecular system can be clarified by the VV 2D correlation analysis. The VV
      2D correlation analysis has also revealed the specific order of the temperature
      induced changes in the hydrogen bonds of NH2 and CONH groups.

PMID- 14661837
TI  - Characterization of tetrol I-1 and (+/-)-anti-BPDE-DNA adducts with solid-matrix
      fluorescence quenching.
AB  - The solid-matrix fluorescence (SMF) quenching of (+/-)-anti-benzo[a]pyrene-trans
      7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adducts and a hydrolysis product of the
      DNA adducts, tetrol I-1, were investigated by using thallium nitrate and sodium
      iodide to quench the SMF. Several fluorescence quenching models were evaluated
      for both (+/-)-anti-BPDE-DNA adducts and tetrol I-1. The SMF quenching phenomena
      were quite different with the two salts for the (+/-)-anti-BPDE-DNA adducts and
      tetrol I-1. Generally, with thallium nitrate as a quencher, a two-site model with
      two independent quenching sites was applicable to both the (+/-)-anti-BPDE-DNA
      adducts and tetrol I-1 data. However, with sodium iodide, the SMF quenching data
      for tetrol I-1 were fit to the sphere of action model, but the (+/-)-anti-BPDE
      DNA adducts SMF quenching data were qualitatively related to a BET isotherm. From
      the SMF quenching data, unique information was acquired for the quasi
      intercalated BPDE-DNA adducts and the external form of the BPDE-DNA adducts. In
      addition, insights were obtained on how the adsorbed salts interacted with the
      solid matrix and with the (+/-)-anti-BPDE-DNA adducts and tetrol I-1.

PMID- 14661838
TI  - Speciation of new tri- and tetra-glucoconjugated tetrapyrrolic macrocycles
      (porphyrins and chlorins): an electronic molecular spectroscopy study.
AB  - In this work, we study the physicochemical properties of some newly developed
      glycoconjugated photosensitizers that can be used in photodynamic therapy (PDT)
      of cancers: meso-tri- and tetra-(meta-O-beta-D-glucosyloxyphenyl)porphyrins and
      meso-, tri-, and tetra-(meta-O-beta-D-glucosyloxyphenyl)chlorins. Their
      properties are compared to the non-glycosylated hydroxylated parent compounds
      meso-tetra-(meta-hydroxyphenyl) porphyrin and meso-tetra-(meta
      hydroxyphenyl)chlorin. It was found that at the ground state, all porphyrins
      present, independent of the substitution, have the same mean ionization constant
      (pKa = 2.7), corresponding to two indistiguishable steps of protonation of
      tetrapyrrolic nitrogens. On the other hand, in the case of chlorins, one proton
      process can be observed and the corresponding nitrogen exhibits a slightly
      superior basicity (pKa = 3.0) with respect to porphyrins. Hydroxylated compounds
      present a second transition at high pH corresponding to the ionization of phenol
      groups (pKa = 10.5). Consequently, all photosensitizers are not charged at
      physiological pH (approximately 7.4), and so the ionization process does not
      influence their activity in biological media. Ionization induces very important
      variations in photosensitizer absorption and emission spectra. For example,
      absorption in the red region (band V), one of the most important characteristics
      of a good photosensitizer, is only important for diprotonated porphyrins and
      neutral chlorins. As far as fluorescence emission is concerned, neutral chlorins
      are almost six times more fluorescent than the corresponding neutral porphyrins
      (phi(chlorin)/phi(porphyrin) approximately = 6). It should be emphasized that the
      spectra modifications induced by pH variations can find interesting applications
      in the optimization of visible and fluorescence detection in high-performance
      liquid chromatography (HPLC) as well as in the development of direct, rapid
      fluorimetric analytical methods.

PMID- 14661839
TI  - Resonance Raman spectroscopy of photolabile transition metal carbonyls:
      controlled photoalteration with continuous wave lasers to record spectra of
      reactants or transient species.
AB  - A method has been developed that enables resonance Raman spectra of photolabile
      species in solution to be recorded under conditions where the level of
      photoalteration is controlled: a low level enables reactant spectra to be
      recorded, whereas a high level enables the spectra of short-lived transient
      species to be recorded in real time using continuous-wave (CW) lasers and
      standard Raman detection equipment. The design includes a sealed flow system,
      enabling air-sensitive species to be studied under an inert atmosphere. A simple
      theoretical model has been developed to aid the interpretation of experimental
      results, and its applicability is demonstrated. Controlled photoalteration and
      its theory are demonstrated with 413.1-nm excitation of carbonmonoxymyoglobin
      (MbCO), which generates deoxymyoglobin (deoxy-Mb) on photolysis, and for which
      the spectra of both species are well established. The methods have also been
      applied to two air-sensitive, photolabile transition metal carbonyls using 514.5
      nm wavelength excitation: for Cp2Mo2(CO)6 (Cp = eta5-C5H5), increasing levels of
      photoalteration result only in a decrease in the parent band intensities,
      relative to the solvent bands; for Cp2Fe2(CO)4, increasing levels of
      photoalteration result in the appearance of additional bands that are assigned to
      the transient species CpFe(mu-CO)3FeCp, formed following the loss of a CO ligand.

PMID- 14661840
TI  - P-N bond length alterations monitored by infrared absorption and Fourier
      transform Raman spectroscopy in combination with density functional theory
      calculations.
AB  - Fourier transform (FT) Raman and infrared spectroscopy in combination with
      density functional theory calculations have been applied to the vibrational
      characterization of the dimeric zinc diphenylphosphanyl(trimethylsilyl)amide
      complex [(Me3Si)2NZnPh2PNSiMe3]2 and the ortho-metallated species [Li(o
      C6H4PPh2NSiMe3)]2 x Et2O in relation to their parent starting materials
      diphenylphosphanyl (trimethylsilyl)amine Ph2P-N(H)SiMe3 and iminophosphorane
      Ph3P=NSiMe3. The spectroscopic changes evidenced in the spectra were correlated
      with the structural parameters in order to provide insight as to what extent the
      P-N bond is affected by the coordination to the metal center. The employment of
      density functional theory (DFT) calculations in addition to these spectroscopic
      methods offers the possibility of predicting whether the Lewis-basic imido
      nitrogen atom is involved in coordination not only in the solid state, but also
      in the gas phase.

PMID- 14661841
TI  - Surface-enhanced resonance Raman scattering of black inkjet dyes in solution and
      in situ printed onto paper.
AB  - Understanding the changes that occur when dyes are absorbed onto paper is crucial
      for the design of new inkjet dyes. This problem is particularly difficult for
      black dyes that have complex chromophores, and as a result, spectroscopic
      information on electronic and structural changes can be of importance. Surface
      enhanced resonance Raman scattering (SERRS) and electronic structure calculations
      were used to probe in situ changes in the chromophore in black di-azo dyes
      printed onto paper. The data indicate that the low-energy chromophore is due
      mainly to the hydrazone group and the high-energy chromophore to both the azo and
      hydrazone groups. A comparison of SERRS from the dyes adsorbed onto silver
      particles in suspension and from the dyes on paper demonstrated a broadening of
      the chromophore into the red for both dyes and evidence of a structural change in
      one dye.

PMID- 14661842
TI  - Characterization of the electrochemical reactions in the Li(1+x)V3O8/Li cell by
      soft X-ray absorption spectroscopy and two-dimensional correlation analysis.
AB  - We applied soft X-ray absorption spectroscopy (XAS) and two-dimensional (2D)
      correlation analysis to the first lithium insertion-extraction cycle in a
      Li(1+x)V3O8/Li cell in order to investigate the electrochemical reactions of
      lithium with the Li(1+x)V3O8 electrode. The V L(II,III)-edge and O K-edge spectra
      of the Li(1+x)V3O8 electrode were obtained for varying electrode lithium content.
      The insertion of lithium leads to the reduction of the V5+ species present in the
      pristine Li(1+x)V3O8 electrode, and to the red shift and the broadening of the
      spectral features of the V L(II,III) edge compared to those of the pristine
      electrode. In the extraction process, the main spectral features at the highest
      value of the extraction of lithium show some differences compared to the features
      of the pristine electrode spectrum due to the residual lithium ions in the
      Li(1+x)V3O8 structure. The O K-edge spectra revealed that the insertion of
      lithium mainly affects the V 4sp-O 2p bonds and consequently induces a change in
      bonding geometry. The 2D correlation analysis of these spectra clearly shows that
      V-O bonds are significantly perturbed by the insertion-extraction of lithium into
      the Li(1+x)V3O8 electrode.

PMID- 14661843
TI  - Two-dimensional correlation spectroscopy: effect of reference spectrum on noise
      free and noisy spectra.
AB  - It has been shown that for two-dimensional (2D) correlation analysis with a
      perturbation average, the first or the last spectrum in the data set as a
      reference provides identical qualitative results. On the other hand, selection of
      the reference spectrum significantly different from the spectra used for 2D
      correlation analysis may complicate interpretation of the contour plots and in
      consequence lead to erroneous results. The effect of noise is relatively small
      when 2D correlation spectra are calculated without the reference spectrum. For
      the other reference spectra the magnitude of the noise effect is comparable. In
      all cases, the asynchronous spectra are more strongly affected by the noise as
      compared to the synchronous spectra.

PMID- 14661844
TI  - Moving window two-dimensional correlation spectroscopy and determination of
      signal-to-noise threshold in correlation spectra.
AB  - In this paper we report two new developments in two-dimensional (2D) correlation
      spectroscopy; one is the combination of the moving window concept with 2D
      spectroscopy to facilitate the analysis of complex data sets, and the other is
      the definition of the noise level in synchronous/asynchronous maps. A graphical
      criterion for the latter is also proposed. The combination of the moving window
      concept with correlation spectra allows one to split a large data matrix into
      smaller and simpler subsets and to analyze them instead of computing overall
      correlation. A three-component system that mimics a consecutive chemical reaction
      is used as a model for the illustration of the two ideas. Both types of
      correlation matrices, variable-variable and sample-sample, are analyzed, and a
      very good agreement between the two is met. The proposed innovations enable one
      to comprehend the complexity of the data to be analyzed by 2D spectroscopy and
      thus to avoid the risks of over-interpretation, liable to occur whenever improper
      caution about the number of co-existing species in the system is taken.

PMID- 14661845
TI  - Near-infrared spectroscopic monitoring of a series of industrial batch processes
      using a bilinear grey model.
AB  - A good process understanding is the foundation for process optimization, process
      monitoring, end-point detection, and estimation of the end-product quality.
      Performing good process measurements and the construction of process models will
      contribute to a better process understanding. To improve the process knowledge it
      is common to build process models. These models are often based on first
      principles such as kinetic rates or mass balances. These types of models are also
      known as hard or white models. White models are characterized by being generally
      applicable but often having only a reasonable fit to real process data. Other
      commonly used types of models are empirical or black-box models such as
      regression and neural nets. Black-box models are characterized by having a good
      data fit but they lack a chemically meaningful model interpretation. Alternative
      models are grey models, which are combinations of white models and black models.
      The aim of a grey model is to combine the advantages of both black-box models and
      white models. In a qualitative case study of monitoring industrial batches using
      near-infrared (NIR) spectroscopy, it is shown that grey models are a good tool
      for detecting batch-to-batch variations and an excellent tool for process
      diagnosis compared to common spectroscopic monitoring tools.

PMID- 14661846
TI  - Emission spectroscopy for coal-fired cyclone furnace diagnostics.
AB  - Using a spectrograph and charge-coupled device (CCD) camera, ultraviolet and
      visible light emission spectra were obtained from a coal-burning electric
      utility's cyclone furnaces operating at either fuel-rich or fuel-lean conditions.
      The aim of this effort is to identify light emission signals that can be related
      to a cyclone furnace's operating condition in order to adjust its air/fuel ratio
      to minimize pollutant production. Emission spectra at the burner and outlet ends
      of cyclone furnaces were obtained. Spectra from all cyclone burners show emission
      lines for the trace elements Li, Na, K, and Rb, as well as the molecular species
      OH and CaOH. The Ca emission line is detected at the burner end of both the fuel
      rich and fuel-lean cyclone furnaces but is not detected at the outlet ends of
      either furnace type. Along with the disappearance of Ca is a concomitant increase
      in the CaOH signal at the outlet end of both types of furnaces. The OH signal
      strength is in general stronger when viewing at the burner end rather than the
      exhaust end of both the fuel-rich and fuel-lean cyclone furnaces, probably due to
      high, non-equilibrium amounts of OH present inside the furnace. Only one
      molecular species was detected that could be used as a measure of air/fuel ratio:
      MgOH. It was detected at the burner end of fuel-rich cyclone furnaces but not
      detected in fuel-lean cyclone furnaces. More direct markers of air/fuel ratio,
      such as CO and O2 emission, were not detected, probably due to the generally weak
      nature of molecular emission relative to ambient blackbody emission present in
      the cyclone furnaces, even at ultraviolet wavelengths.

PMID- 14661847
TI  - Aqueous solutions of uranium(VI) as studied by time-resolved emission
      spectroscopy: a round-robin test.
AB  - Results of an inter-laboratory round-robin study of the application of time
      resolved emission spectroscopy (TRES) to the speciation of uranium(VI) in aqueous
      media are presented. The round-robin study involved 13 independent laboratories,
      using various instrumentation and data analysis methods. Samples were prepared
      based on appropriate speciation diagrams and, in general, were found to be
      chemically stable for at least six months. Four different types of aqueous uranyl
      solutions were studied: (1) acidic medium where UO2(2+)aq is the single emitting
      species, (2) uranyl in the presence of fluoride ions, (3) uranyl in the presence
      of sulfate ions, and (4) uranyl in aqueous solutions at different pH, promoting
      the formation of hydrolyzed species. Results between the laboratories are
      compared in terms of the number of decay components, luminescence lifetimes, and
      spectral band positions. The successes and limitations of TRES in uranyl analysis
      and speciation in aqueous solutions are discussed.

PMID- 14661848
TI  - Liquid/liquid optical waveguides using sheath flow as a new tool for
      liquid/liquid interfacial measurements.
AB  - A liquid/liquid optical waveguide was constructed using a sheath flow. Since the
      refractive index of an organic solvent is generally higher than that of water (nD
      = 1.33), light introduced into the inner organic flow should proceed with total
      multi-reflection within the inner flow, so that the inner part of the sheath flow
      acts as the core of an optical waveguide. This sheath flow liquid/liquid optical
      waveguide was stable and showed no substantial background scattering. Moreover,
      it is applicable to both miscible and immiscible liquid/ liquid interfaces. Thus,
      it may become a new tool for studying liquid/liquid interfaces as well as for
      sensitive optical measurements.

PMID- 14661849
TI  - Identification of oil contaminants on polymer coated beverage cans using
      fluorescence spectroscopy.
AB  - In a recent publication we introduced a novel method for detection of impurities
      on beverage can surfaces using Raman spectroscopy. While investigating the
      technique, limitations emerged due to the low sensitivity of Raman scatter. This
      is a particular problem with the largest contributor of impurities in beverage
      cans: lubricants employed in the manufacturing process. This paper presents an
      alternative approach, using the more sensitive technique of fluorescence
      spectroscopy to tackle the same problem. Measurements using fluorescence
      spectroscopy were conducted indirectly in a cuvette as well as directly on a can
      surface with the aid of fiber optics. The chemometrics methods of linear
      discriminant analysis (LDA) and principal components analysis (PCA) were used to
      classify acquired spectra as belonging to one of the 16 investigated lubricants.
      Fiberoptic scans revealed that a successful detection and recognition of
      lubricant is possible down to a volume of 0.5 microL deposited on the can
      surface. Contaminant detection was possible at even lower levels down to 0.01
      microL, but reliable identification proved difficult at such low volumes.
      Indirect measurements of lubricants dissolved in cyclohexane yielded the lowest
      detection limits between 1-0.1 ppb.

PMID- 14661850
TI  - Two-dimensional correlation analysis of unevenly spaced spectral data.

PMID- 14661851
TI  - Synthesis and antiviral activity of novel trans-2,2-dimethyl cyclopropyl
      nucleosides.
AB  - Novel trans-2,2-dimethylcyclopropyl nucleosides were synthesized as potential
      antiviral agents. The key intermediate, 3, was synthesized via five steps from
      ethyl chrysanthemate and condensed with purine bases using the Mitsunobu reaction
      to give six cyclopropyl nucleosides. These synthesized nucleosides did not show
      any significant antiviral activity against HSV-1, HSV-2, EMCV, Cox B3, or VSV, at
      concentrations up to 100 microM.

PMID- 14661852
TI  - Synthesis and characterization of the tumor targeting mitoxantrone-insulin
      conjugate.
AB  - Anticancer drugs have serious side effects arising from their poor malignant
      cells selectivity. Since insulin receptors highly express on the cytomembrane of
      some kind of tumor cells, using insulin as the vector was expected to reduce
      serious side effects of the drugs. The objective of this study was to evaluate
      the tumor targeting effect of the newly synthesized mitoxantrone-insulin
      conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials
      showed MIT-INS were stable in buffers with different pH (2-8) at 37 degrees C
      within 120 h (less than 3% of free MIT released), and were also stable in mouse
      plasma within 48 h (less than 1% of free MIT released). In vivo study on tumor
      bearing mice showed that, compared with MIT [75.92 microg x h/g of the area under
      the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the
      conjugates had better tumor-targeting efficiency with enhanced tumor AUC of
      126.53 microg x h/g and MTR of 151.95 h. The conjugate had much lower toxicity to
      most other tissues with targeting indexes (TIC) no larger than 0.3 besides good
      tumor targeting efficiency with TIC of 1.67. The results suggest the feasibility
      to promote the curative effect in cancer chemotherapy by using insulin as the
      vector of anti-cancer drugs.

PMID- 14661853
TI  - Diterpenoids from the stem barks of Croton robustus.
AB  - Three compounds were isolated from the stem barks of Croton robustus. Their
      structures were elucidated as trachyloban-19-oic acid, trachyloban-19-ol and
      poilaneic acid by spectroscopic analysis. Among them, trachyloban-19-ol and
      methyl trachyloban-19-oate exhibited weak cytotoxic activity against gastric
      carcinoma and colon carcinoma with ED50 of 9.2, 9.6 and 8.3, 9.1 microg/mL,
      respectively.

PMID- 14661854
TI  - Constituents from the non-polar fraction of Artemisia apiacea.
AB  - Five compounds of terpenoids and coumarins were isolated from the non-polar
      fraction of Artemisia apiacea by open column chromatography. Their structures
      were elucidated as alpha-amyrin (1), beta-amyrin (2), beta-sitosterol (3), 5,6,7
      trimethoxycoumarin (4) and 6-methoxy-7,8-methylenedioxycoumarin (5) by chemical
      and spectroscopic analysis. This is the first report of the isolation of alpha
      amyrin, beta-amyrin, 5,6,7-trimethoxycoumarin and 6-methoxy-7,8
      methylenedioxycoumarin from this plant.

PMID- 14661855
TI  - Ginsenoside Rb1: the anti-ulcer constituent from the head of Panax ginseng.
AB  - We previously reported that the butanol (BuOH) fraction of the head of Panax
      ginseng exhibited gastroprotective activity in peptic and chronic ulcer models.
      In order to identify the active constituent, an activity-guided isolation of the
      BuOH faction was conducted with a HCl x ethanol-induced gastric lesion model. The
      BuOH fraction was passed through a silica-gel column using a chloroform-methanol
      gradient solvent system, and six fractions (frs. 1-6) were obtained. The active
      fr. 5 was further separated by silica-gel column, to yield 6 subfractions
      (subfrs. a-f). Subfr. d was composed of ginsenosides Re, Rc and Rb1. The most
      active constituent was ginsenoside Rb1 (GRb1), a protopanaxadiol glycoside, which
      was investigated for its anti-ulcer effect. Gastric injury induced by HCl x
      ethanol, indomethacin and pyloric ligation (Shay ulcer) was apparently reduced
      with oral GRb1 doses of 150 and 300 mg/kg. GRb1 at these dosage significantly
      increased the amount of mucus secretion in an ethanol-induced model. The anti
      ulcer effects were consistent with the result of histological examination. These
      results suggest that the major active constituent in the head of Panax ginseng is
      GRb1, and that anti-ulcer effect is produced through an increase in mucus
      secretion.

PMID- 14661856
TI  - Triterpenoids from Schisandra henryi with cytotoxic effect on leukemia and Hela
      cells in vitro.
AB  - Four known lanostane triterpenoids, schiprolactone A (1), schisanlactone B (2),
      nigranoic acid (3) and schisandronic acid (4) were isolated from the stems of
      Schisandra henryi for the first time. Their structures were characterized by IR,
      MS and NMR techniques. Compounds 1, 2 and 4 showed moderate cytotoxic activity
      against Leukemia cells in vitro. Cytotoxic activity of compounds 1-4 showed IC50
      of 0.0097, 0.01, 0.097 and 0.0099 micromol/mL respectively toward Leukemia cells
      and IC50 of 0.097, 0.1, 0.097 and 0.099 micromol/mL toward Hela cells
      respectively. It is the first report that these compounds possess cytotoxic
      activity on Leukemia and Hela cells.

PMID- 14661857
TI  - Herbal extract prevents bone loss in ovariectomized rats.
AB  - This research aims to test a new drug candidate based on a traditional medicinal
      herb, F1, an herbal extract obtained from Astragalus membranaceus and its main
      ingredient, 1-monolinolein that may have fewer side effects and less uterine
      hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and
      Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were
      induced through a calcium-deficient diet and inhibition effects were measured. In
      vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At
      necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and
      lumbar vertebra were measured bone histomorphology. In results, cell
      proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not
      increased significantly compared to the control. The F1 inhibited osteoclast
      development (IC25 = 3.37 x 10(-5) mg/mL) less than 17beta-estradiol. The OVX rats
      administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the
      tibia significantly (136.3 +/- 4.2% and 138.5 +/- 10.3% of control). In
      conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did
      not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of
      the herbal extract, did not inhibit bone loss.

PMID- 14661858
TI  - Cytotoxic effects of sesquiterpene lactones from the flowers of Hemisteptia
      lyrata B.
AB  - Four guaia-12,6-olide type sesquiterpene lactones, aguerin B (1), 8alpha
      acetoxyzaluzanin C (2), cynaropicrin (3), and deacylcynaropicrin (4), were
      isolated from the flowers of Hemisteptia lyrata Bunge. It is the first report on
      the isolation of compounds 1-4 from Hemisteptia species. All the isolates (1-4)
      were examined for their cytotoxic activity against SK-OV-3, LOX-IMVI, A549, MCF
      7, PC-3, and HCT-15 human cancer cell lines.

PMID- 14661859
TI  - Effects of Eucommiae Cortex on osteoblast-like cell proliferation and osteoclast
      inhibition.
AB  - Methanol extract (MeOH), n-hexane (Hx), chloroform (CHCl3), ethyl acetate (EA),
      butanol (BuOH) and aqueous (H2O) fractions of Eucommiae Cortex including
      geniposidic acid (GA), geniposide (GP) and aucubin (AU) were tested for their
      therapeutic efficacy on osteoporosis. The contents of GA, GP and AU in the cortex
      and leaf of Eucommia ulmoides Oliver were quantified by HPLC. The effect of
      Eucommiae Cortex on the induction of growth hormone (GH) release was studied by
      using rat pituitary cells. The proliferation of osteoblast-like cells increased
      by herbal extracts was assayed using a tetrazolium (MTT), alkaline phosphatase
      (ALP) activity, and [3H]-proline incorporation assays. The inhibition of
      osteoclast was studied by using the coculture of mouse bone marrow cells and ST-2
      cells. As a result, the GA, GP and AU were present in the cortex more than in the
      leaf of E. ulmoides Oliver. The MeOH (1 mg/mL), Hx, CHCl3 and EA fractions (each
      20 microg/mL) had potent induction of GH release. The CHCl3 exhibited the potent
      proliferation of osteoblasts. The AU, GP and GA were increased proliferation of
      osteoblasts. In addition, GA (IC50: 4.43 x 10(-7) M), AU and GP were
      significantly inhibited proliferation of osteoclast. In summary, it is thought
      that the components in a part of the fractions of Eucommiae Cortex participate in
      each step of mechanism for activating osteoblast to facilitate osteogenesis, and
      suppress osteoclast activity to inhibit osteolysis.

PMID- 14661860
TI  - JNK/SAPK is required in nitric oxide-induced apoptosis in osteoblasts.
AB  - Nitric oxide(NO) induces apoptosis in human osteoblasts. Treatment with exogenous
      NO donors, SNAP (S-Nitroso-N-acetylpenicillamine) and SNP (sodium nitroprusside),
      to MG-63 osteoblasts resulted in apoptotic morphological changes, as shown by a
      bright blue-fluorescent condensed nuclei and chromatin fragmentation by
      fluorescence microscope of Hoechst 33258-staining. The activities of caspase-9
      and the subsequent caspase-3-like cysteine proteases were increased during NO
      induced cell death. Pretreatment with Z-VAD-FMK (a pan-caspase inhibitor) or Ac
      DEVD-CHO (a specific caspase-3 inhibitor) abrogated the NO-induced cell death.
      The NO donor markedly activated JNK, a stress-activated protein kinase in the
      human osteoblasts. This study showed that the inhibition of the JNK pathway
      markedly reduced NO-induced cell death. But neither PD98059 (MEK inhibitor) nor
      SB203580 (p38 MAPK inhibitor) had any effect on NO-induced death. Taken together,
      these results suggest that JNK/SAPK may be related to NO-induced apoptosis in MG
      63 human osteoblasts.

PMID- 14661861
TI  - Acute effects of 2-bromopropane and 1,2-dibromopropane on hepatotoxic and
      immunotoxic parameters in female BALB/c mice.
AB  - In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its
      analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice.
      The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP
      at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized
      intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights
      of the spleen and thymus weights and decreased the number of splenic cells. In
      addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs.
      Meanwhile, only the antibody response was significantly suppressed by treatment
      with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1,2-DBP
      on the hepatotoxic parameters were compared in female BALB/c mice. When mice were
      treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the
      activities of serum alanine aminotransferase and aspartate aminotransferase
      elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic
      content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were
      increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200
      also contributes to the immnunotoxicity, although 2-BP is a major component.

PMID- 14661862
TI  - Differential effects of typical and atypical neuroleptics on mitochondrial
      function in vitro.
AB  - A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical
      (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested
      for effects on integrated bioenergetic functions of isolated rat liver
      mitochondria. Polarographic measurement of oxygen consumption in freshly isolated
      mitochondria showed that electron transfer activity at respiratory complex I is
      inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by
      clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as
      modest uncouplers of oxidative phosphorylation. The typical neuroleptics
      inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a
      direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q
      reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less
      than that for the typical neuroleptics. Clozapine and olanzapine had only slight
      effects on NADH-coenzyme Q reductase activity, even at 200 microM. The relative
      potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic
      function is similar to their relative potencies as risk factors in the reported
      incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This
      suggests that compromised bioenergetic function may be involved in the cellular
      pathology underlying TD.

PMID- 14661863
TI  - Antiviral and tumoricidal activities of alginate-stimulated macrophages are
      mediated by different mechanisms.
AB  - Macrophages play an important role in host defenses by killing tumors and virus
      infections and producing secretory products. High mannuronic acid (HMA)
      containing alginate was examined to determine the mechanisms by which HMA
      activated macrophages resist infection with HSV-1 and inhibit the growth of tumor
      cells. The ability of macrophages to resist infection with HSV-1 or to inhibit
      the growth of tumor cells was assessed following treatment with HMA alginate in
      the presence of either antibodies to various cytokines or inhibitors/scavengers
      of toxic macrophage products. Only antibodies to IFN-alpha/beta were able to
      abrogate the protective effects of HMA alginate in macrophages infected with HSV
      1, suggesting that the antiviral activity induced by this immunomodulator was
      mediated by the production of IFN-beta. In contrast, anti-TNF-alpha, anti-IFN and
      inhibitors of nitric oxide and reactive oxygen species were all able to partially
      abrogate HMA-induced cytostatic activity, suggesting that multiple mechanisms are
      involved in macrophage cytostasis. These results indicate that the HMA-induced
      intrinsic antiviral and extrinsic cytotoxic activites are mediated by different
      mechanisms.

PMID- 14661864
TI  - Polymorphism in CYP2C9 as a non-critical factor of warfarin dosage adjustment in
      Korean patients.
AB  - Cytochrome P4502C9(CYP2C9) is largely responsible for terminating anticoagulant
      effect by hydroxylation of S-warfarin to inactive metabolites. Mutations in the
      CYP2C9 gene result in the expression of allelic variants, CYP2C9*2 and CYP2C9*3
      with reduced enzyme activity compared to wild type CYP2C9*1. The aim of this
      study was to assess relationship between requirement of warfarin dose and
      polymorphism in CYP2C9 in Korean population. Patients on warfarin therapy for
      longer than 1 year were included from July 1999 to December 2000 and categorized
      as one of four groups; regular dose non-bleeding, regular dose bleeding, low dose
      non-bleeding and low dose bleeding. Low dose was defined as less than 10 mg/week
      for 3 consecutive monthly follow-ups. Bleeding complications included minor and
      major bleedings. Blood samples were processed for DNA extraction, genotyping and
      sequencing to detect polymorphism in CYP2C9. Demographic data, warfarin dose per
      week, prothrombin time (INR), indications and co-morbid diseases were assessed
      for each group. Total 90 patients on warfarin were evaluated; The low dose group
      has taken warfarin 7.6 +/- 1.7 mg/week, which was significantly lower than 31.4
      +/- 0.9 mg/week in the regular dose group (p<0.0001). The measured INR in the low
      dose group was similar to that of the regular dose group (2.3 +/- 0.7 vs. 2.3 +/-
      0.6, p=0.9). Even though there was a higher possibility of CYP2C9 variation in
      the low dose group, no polymorphism in CYP2C9 was detected. All patients were
      homozygous C416 in exon 3 for CYP2C9*2 and A1061 in exon 7 for CYP2C9*3. The DNA
      sequencing data confirmed the homozygous C416 and A1061 alleles. In conclusion,
      polymorphism in CYP2C9 is not a critical factor for assessing warfarin dose
      requirement and risk of bleeding complications in a Korean population.

PMID- 14661865
TI  - Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl
      methylcellulose.
AB  - A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl
      methylcellulose was prepared to develop a buccal patch and the effects of
      composition of the film on adhesion time, swelling ratio, and dissolution of the
      film were studied. The effects of plasticizers or penetration enhancers on the
      release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding
      between Carbopol and Poloxamer played important role in reducing swelling ratio
      and dissolution rate of polymer film and increasing adhesion time. The swelling
      ratio of the composite film was significantly reduced and the adhesion time was
      increased when compared with Carbopol film. As the ratio of Poloxamer to
      hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of
      TAA decreased. However, no further significant decrease of release rate was
      observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film
      containing polyethylene glycol 400, a plasticizer, showed the highest release
      rate followed by triethyl citrate, and castor oil. The release rate of TAA from
      the polymeric film containing permeation enhancers was slower than that from the
      control without enhancers. Therefore, these observations indicated that a
      preparation of a buccal patch is feasible with the polymeric film composed of
      Cabopol, Poloxamer and hydropropyl methylcellulose.

PMID- 14661866
TI  - Pharmacokinetics of tolbutamide after oral administration to rabbits with folate
      induced renal failure.
AB  - The pharmacokinetic of tolbutamide was studied after the oral administration to
      normal rabbits or rabbits with mild to medium folate-induced renal failure. The
      plasma concentrations of tolbutamide were significantly elevated (p<0.05) during
      9 to 24 h in rabbits with mild or medium folate-induced renal failure.
      Consequently, the area under the plasma concentration-time curves (AUC) was
      significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal
      failure rabbits (i.e., 2906 microg/mL x h for mild renal failure and 4074
      microg/mL x h for moderate renal failure) than that in normal rabbits (i.e., 2295
      microg/mL x h). The cumulative urinary excretion of tolbutamide was significantly
      depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg)
      compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate
      constant (Kel) of tolbutamide was significantly decreased in medium renal failure
      rabbits (i.e., 0.027 h(-1)) than that in normal rabbits (i.e., 0.044 h(-1)); As a
      result, the terminal half-life of tolbutamide in medium folate-induced renal
      failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in
      normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is
      consistent with the hypothesis that the alteration is mediated by the depressed
      metabolic elimination of the drug by the induction of renal failure. Therefore,
      these observations indicated that the dosage adjustment may be necessary for
      tolbutamide in patients with renal insufficiency.

PMID- 14661867
TI  - Dextran sulfate as a material for the preparation of a membrane for
      immunoisolation.
AB  - Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed
      in an artificial membrane to be protected from the host immune system, is
      expected to be a promising medical device to treat patients who suffer from
      insulin-dependent diabetes. Our strategy for preparation of a bioartificial
      pancreas involves utilizing a membrane including polymeric materials that can
      inhibit the complement. In our series of studies, we have examined interactions
      of various polyanions with the complement system to search for potential
      complement inhibitors. In this study, we concentrated our efforts to clarify the
      effects of dextran sulfate on the complement system. All of the dextran sulfates
      examined inhibited the complement activation through both classical and
      alternative pathways as previously reported. In addition to their inhibitory
      effects, a certain species of dextran sulfate (molecular mass 10 kDa, degree of
      sulfonation in a pyranose ring 1.99) specifically degraded C3 without complement
      activation and, thus, anaphylatoxins that trigger inflammatory reactions were not
      generated. These facts suggest that a membrane including dextran sulfate
      effectively protects the islet cells from humoral immunity in addition to not
      triggering inflammatory reactions. These properties of the membrane make it
      suitable for a bioratificial pancreas.

PMID- 14661868
TI  - Preparation of a stable phospholipid monolayer grafted onto a methacryloyl
      terminated substrate as blood compatible materials.
AB  - We have prepared a surface-grafted phospholipid monolayer by in situ
      polymerization carried out at the interface between a pre-assembled phospholipid
      monolayer and a methacryloyl-terminated substrate. The phospholipid containing an
      acryloyl moiety, 1-stearoyl-2-[12-(acryloyloxy)-dodecanoyll-sn-glycero-3
      phosphocholine (acryloyl-PC), was pre-assembled by vesicle fusion onto
      methacryloyl-terminated substrates which were silanized with 3
      (trimethoxysilyl)propyl methacrylate (TSM). The acryloyl-PC monolayer and
      methacryloyl-terminated substrates were then polymerized in situ by adding a
      water-soluble initiator, 2,2-azobis(2-methylpropionamidine) dihydrochloride
      (AAPD), at 60 degrees C for 15 min. Atomic force microscopy (AFM) and X-ray
      photoelectron spectroscopy (XPS) measurements indicated that the polymerized
      phospholipid surface on the TSM-silanized substrates formed a lipid monolayer
      structure with some defects. The polymerized phospholipid surfaces also showed
      good stability in methanol due to chemical bonding to solid surfaces. The
      grafting efficiency of acryloyl-PC monolayer on the TSM substrate, which was
      calculated by the relative carbon ratio of the polymerized acryloyl-PC monolayer
      on TSM substrate before and after methanol washing, was 94.5%. For comparative
      analysis, the acryloyl-PC monolayer was also polymerized onto dimethyl-terminated
      substrates silanized with dichlorodimethylsilane (DCM). In the absence of surface
      grafting moieties on solid substrates, the laterally polymerized acryloyl-PC
      monolayer physically adsorbed on substrates was easily removed in an organic
      solvent. The surface-grafted phospholipid monolayer was also greatly effective in
      the prevention of platelet adhesion.

PMID- 14661869
TI  - In situ accelerated degradation of polyoxyethylene/poly(epsilon-caprolactone)
      multiblock copolymer by moderate thermal treatment.
AB  - Alternating amphiphilic multiblock copolymers, consisting of polyoxyethylene
      (POE) and poly(epsilon-caprolactone) (PCL) of various lengths, were synthesized
      by a polycondensation reaction between dicarboxylated PEG and dihydroxyl PCL. The
      polymer formed a physical hydrogel by PCL crystallization. For in vitro
      hydrolysis in phosphate-buffered saline solution, the change of molecular weight
      depended on the composing block length of POE. The polymer with longer POE showed
      a faster decline in molecular weight. The mass remaining at the end of two weeks
      at 25 degrees C was more than 95 w%. However, when the swollen hydrogels were
      exposed to temperatures slightly above PCL melting point for 30 min, the
      degradation rate was accelerated and the mass remaining dropped to less than 10
      wt% in one week. In vivo degradation after hydrogel implantation, the polymer
      degraded as under in vitro. However, the implant irradiated with infrared (IR)
      accelerated its degradation similar to a treatment with elevated temperature.

PMID- 14661870
TI  - Cell attachment and biocompatibility of polytetrafluoroethylene (PTFE) treated
      with glow-discharge plasma of mixed ammonia and oxygen.
AB  - The plasma generated from a gas mixture of NH3 plus O2 (NH3 + O2) has been used
      to impart unique chemical and biological characteristics to
      polytetrafluoroethylene (PTFE). PTFE treated with NH3 + O2 plasma was
      physiochemically distinct from surfaces treated with plasma of either NH3 or O2
      alone, as determined by electron spectroscopy for chemical analysis (ESCA). The
      contact angle analysis revealed that the PTFE surfaces became less hydrophobic
      after plasma treatments. ESCA results indicate the presence of oxygen-containing
      groups and nitrogen-containing groups at the plasma-treated surfaces. PTFE
      treated with NH3 + O2 plasma resisted the attachment of platelets and leukocytes
      in a manner similar to untreated PTFE; however, the attachment of bovine aorta
      endothelial cells was substantially increased. Once attached, these cells grew to
      confluency. The increased endothelial cell attachment was higher than that
      observed following plasma treatment with each gas used separately, which could be
      attributed to the considerable amount of CF(OR)2-CF2 formed on the NH3 + O2
      plasma-treated PTFE surface. At 14 days after subcutaneous implantation in rats,
      the PTFE wafers treated with NH3 + O2 plasma demonstrated less encapsulation and
      lower levels of inflammatory cells compared to controls. Collectively, the
      results suggest that NH3 + O2 plasma treatment imparts a unique character to PTFE
      and could be useful in certain in vivo applications.

PMID- 14661871
TI  - Photografting of poly(hydroxylethyl acrylate) onto porous polyurethane scaffolds
      to improve their endothelial cell compatibility.
AB  - In order to improve the cytocompatibility of polyurethane (PU) porous scaffolds
      obtained by thermally-induced phase separation, poly(hydroxylethyl acrylate)
      (PHEA) was covalently immobilized by grafting copolymerization of HEA by photo
      oxidation of the scaffolds and initiation of UV light. FT-IR-ATR spectroscopy and
      X-ray photoelectron spectroscopy (XPS) characterizations confirmed the occurrence
      of the grafting co-polymerization of HEA on the porous PU scaffolds. The
      measurement of water absorption demonstrated the improvement of the
      hydrophilicity after grafting with PHEA. The results obtained in a human
      umbilical vein endothelial cell (HUVEC) culture proved that the porous PU
      scaffold modified with the hydrophilic PHEA had better cytocompatibility than the
      control. The influence of surface pore size on the HUVEC growth behavior was
      assessed regarding cell anchorage, proliferation and viability, as well as
      morphology. An overall increase of cell number and viability with the decrease of
      the surface pore size was found.

PMID- 14661872
TI  - Norfloxacin-releasing urethral catheter for long-term catheterization.
AB  - Norfloxacin-releasing urethral catheters were prepared for the purpose of
      preventing urinary tract infections during long-term catheterization. The outer
      and inner surfaces of the catheters were coated with poly(ethylene-co-vinyl
      acetate) (EVA) and an amphiphilic multiblock co-polymer (PEO2kPDMS), composed of
      poly(ethylene oxide) and poly(dimethyl siloxane). Norfloxacin, a fluoroquinolone
      synthetic antibiotic, was impregnated into a coating layer. The in vitro drug
      release behavior was monitored for 30 days, the surface topography was
      investigated using scanning electron microscopy (SEM) and the antibacterial
      activity against different bacteria implicated in urinary tract infection was
      evaluated by the in vitro inhibition zone test. All the coated catheters showed
      continuous delivery of norfloxacin for up to 30 days owing to hydrophobic natures
      of norfloxacin and EVA. PEO2kPDMS incorporated in a coating layer produced a
      smooth and uniform surface. The coated catheters created considerable inhibition
      zones for 10 days against Escherichia coli. Klebsiella pneumoniae and Proteus
      vulgaris, indicating the continuous release of norfloxacin. Overall, it was
      evident that the catheters coated with EVA/PEO2kPDMS blends containing
      norfloxacin have a promising potential for the clinical use in patients
      undergoing long-term catheterization.

PMID- 14661873
TI  - Gentamicin-releasing urethral catheter for short-term catheterization.
AB  - Urethral catheters, widely used for the drainage of the bladder, are associated
      with most urinary tract infections (UTIs) that account for 40% of all episodes
      occurring in acute-care hospitals. This study aimed to develop a gentamicin
      releasing catheter that effectively prevents UTIs for short-term catheterization.
      For physical loading of gentamicin, the urethral catheters were coated by the
      simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and
      EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the
      molecular weight (MW) and contents of PEO in the blends, various catheter
      surfaces were produced. In vitro drug release studies demonstrated that all the
      coated catheters exhibited sustained release up to 7 days; however, the release
      pattern was significantly dependant on the coating layers. Of the coated
      catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the
      antibacterial activity using an inhibition zone test, since they showed a
      promising drug release behavior and had PEO-rich biocompatible surfaces. In
      accordance with drug release behavior, EVA/PEO-coated catheters exhibited
      antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus
      aureus and Staphylococcus epidermidis. These results imply that the catheters
      coated with EVA/PEO have a potential for short-term catheterization.

PMID- 14661874
TI  - Assessment of fibronectin conformation adsorbed to polytetrafluoroethylene
      surfaces from serum protein mixtures and correlation to support of cell
      attachment in culture.
AB  - Surfaces of polytetrafluoroethylene (PTFE) were exposed to buffered aqueous
      solutions containing radio-labeled human fibronectin ([125I]Fn), Fn/bovine serum
      albumin (BSA) binary mixtures of various ratios or whole human plasma dilutions
      for 1 h. Total adsorbed Fn and albumin adsorption following rinsing was
      quantified on this surface. 125I-labeled monoclonal antibodies against either the
      tenth type-III Fn repeat unit (containing the cell-binding RGDS integrin
      recognition motif) or the Fn amino-terminal domain were used to probe the
      accessibility of each of these respective Fn regions post-adsorption. Human
      umbilical vein endothelial cells (HUVECs) were cultured on PTFE surfaces pre
      exposed to each of these protein adsorption conditions and compared to identical
      conditions on tissue culture polystyrene (TCPS). Fn adsorption to PTFE is
      dependent upon the concentration of albumin co-adsorbing from solution: albumin
      out-competes Fn for PTFE surface sites even at non-physiological Fn/HSA ratios 10
      100-fold biased in Fn. Antibodies against Fn do not readily recognize Fn adsorbed
      on PTFE as the HSA co-adsorption concentration in either binary mixtures or in
      plasma increases, indicating albumin masking of adsorbed Fn. At Fn/HSA ratios
      rich in Fn (1:1, 1:100), albumin co-adsorption actually improves anti-Fn antibody
      recognition of adsorbed Fn. HUVEC attachment efficiency to PTFE after protein
      adsorption correlates with amounts of Fn adsorbed and levels of anti-Fn antibody
      recognition of Fn on PTFE, linking cell attachment to integrin recognition of
      both adsorbed Fn density and Fn adsorbed conformation on PTFE surfaces.

PMID- 14661875
TI  - Effect of drying history on swelling properties and cell attachment to
      oligo(poly(ethylene glycol) fumarate) hydrogels for guided tissue regeneration
      applications.
AB  - In these experiments, the effects of the drying history of hydrogels made from a
      novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF) with two different
      poly(ethylene glycol) (PEG) molecular weights (approximately 920 (1K) and 9110
      (10K) g/mol), were investigated. The hydrogels were either formed, dried and then
      swelled, representing what may occur in the case of a pre-formed membrane for
      guided tissue regeneration, or were formed and swelled immediately, as may occur
      with an injectable material for such applications. Subsequently, swelling
      properties, sol fraction and polymer network structure (as indicated by
      differential scanning calorimetry), as well as attachment of human dermal
      fibroblasts to these hydrogels at 4 and 24 h was examined. It was found that
      drying before swelling caused a significant reduction in final fold swelling of
      OPF hydrogels, regardless of OPF formulation or method of drying (air-dried or
      vacuum-dried) (e.g. PEG 10K swollen first: 13.94 +/- 0.35 vs. vacuum first: 6.53
      +/- 0.12; PEG 1K swollen first: 8.99 +/- 0.47 vs. vacuum first: 2.26 +/- 0.08).
      This decreased swelling correlated to significantly higher cell attachment (%
      seeded) to these hydrogels at 24 h (PEG 10K vacuum first: 21.1 +/- 4.7% vs.
      swollen first: 7.1 +/- 5.5%; PEG 1K vacuum first: 58.2 +/- 2% vs. swollen first:
      7.4 +/- 2.2%). LIVE/DEAD staining followed by microscopic analysis revealed
      attached cells were viable, yet rounded, and that, in the case of the PEG 1K
      dried-first samples, undulations in the surface visible in the hydrated state may
      have affected cell adhesion. Regardless of treatment, all hydrogels showed
      significantly less cell attachment than the tissue culture polystyrene control
      after 24 h (104.9 +/- 4.4%). These results suggest that, by altering the PEG
      molecular weight used in synthesis, OPF hydrogels may be tailored to produce
      desired swelling properties and reduce non-specific cell adhesion for either
      injectable or pre-formed applications, thus providing a potential alternative
      material for use in guided tissue regeneration procedures.

PMID- 14661876
TI  - Surface engineering of biomaterials with plasma techniques.
AB  - In this study, 3 types of plasma techniques, i.e. plasma modification, plasma
      deposition and plasma followed by grafting reaction, are used for the fabrication
      of tools, medical devices and biomaterials. Depending on purpose, bioadhesion of
      cells and biomolecules is either looked for or avoided. Since the mechanisms of
      bioadhesion depend on the characteristics of the surface (hydrophilic or
      hydrophobic), modifying the surface by a treatment will alter the bioadhesion.
      These treatments are developed for the anti-fouling process, the sterilisation
      and the improvement of the formation of biofilms. They have also proved useful
      for the synthesis of biomimicking devices.

PMID- 14661877
TI  - Production of purified polyhydroxyalkanoates (PHAs) for applications in contact
      with blood.
AB  - Samples of olyhydroxyalkanoates (PHAs), polyhydroxybutyrate (PHB) and copolymers
      poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) with 4 and 18 mol%
      hydroxyvalerate, synthesized by the bacteria Ralstonia eutropha B5786, were
      investigated. PHA films in contact with blood did not activate the hemostasis
      system at the level of cell response, but they did activate the coagulation
      system and the complement reaction. To detect biologically-active components in
      the PHAs, a detailed analysis of the composition of the polymers was conducted.
      Gas chromatography-mass spectrometry revealed long-chain fatty acids (FAs) in the
      tested PHAs. Their total concentration in the polymer ranged from tenths of mol%
      to 2-3 mol%, depending on the purification method. C16:0 constituted the largest
      proportion, up to 70%. Of the long-chain hydroxy acids, only beta-OH-C14:0 was
      detected and it did not exceed 0.06 mol%. The analysis of the hemocompatibility
      properties of the PHAs purified by a specialized procedure, including the
      quantitative and morphological estimation of platelets adherent to the surface of
      polymer films, the plasma recalcification time and complement activation studies,
      indicated that PHB and PHBV can be used in contact with blood. It has been found
      out that the lipopolysaccharides of bacteria producing PHAs, which contain mostly
      long-chain hydroxy acids, can be the factor activating the hemostasis systems.
      Thus, the technology of PHA purification must satisfy rather stringent specific
      requirements.

PMID- 14661878
TI  - Penicillin V-conjugated PEG-PAMAM star polymers.
AB  - Starburst PAMAM dendrimers are potential carriers for drug delivery due to their
      unique structure. Drug-delivery scaffolds were designed and built up based on the
      polyethylene glycolpolyamidoamine (PEG-PAMAM) star polymer. Penicillin V was used
      as a model carboxylic group containing drug to conjugate with full- and half
      generation PAMAM dendrimers. G2.5 PAMAM (with 32 carboxylic groups on the
      surface) dendrimers and G3.0 (with 32 primary amine groups on the surface) were
      typically chosen. There are two strategies given in the paper where a drug
      carrying a carboxylic group (e.g. penicillin V) was coupled to star polymer via
      amide and ester bonds, respectively. FT-IR, UV-Vis and 1H-NMR were used to
      characterize the intermediates and drug-star polymer conjugates. A single-strain
      bacterium, Staphylococcus aureus, was grown up for penicillin-conjugated PEG
      PAMAM (G3.0) star polymer activity test. The result verified the bioavailability
      of modified penicillin after the ester bond was cleaved.

PMID- 14661879
TI  - Functionalization of poly-(L-lactic-co-epsilon-caprolactone): effects of surface
      modification on endothelial cell proliferation and hemocompatibility [corrected].
AB  - A copolymer of L-lactic acid and epsilon-caprolactone (PLLACL) was synthesized
      with the aim of preparing a bioartificial, small-diameter and partially
      resorbable vascular graft. The material was submitted to surface
      functionalizations (i.e. chemical modification by means of hydrolytic 'etching'
      and plasma discharge) to promote endothelial cell (EC) adhesion and growth
      avoiding platelet adhesion or coagulation factor absorption. Furthermore, the
      behaviour of human microvascular endothelial cells (HMVEC) seeded on the
      untreated and treated copolymer is described, as well as the platelet adhesion
      and the modifications of coagulation factors determined by the copolymer itself.
      PLLACL in its native state provided little support for EC adhesion. Improved EC
      adherence was obtained when functional groups were provided on the polymer
      surface by surface chemical hydrolysis. HMVEC seeded and cultured on the polymer
      surface did not show any ultrastructural alteration, thus demonstrating the
      absence of the polymer cytotoxicity. Moreover, SEM analysis performed on cold
      plasma modified specimens showed the presence of a subconfluent monolayer of EC,
      with an elongated spread morphology. Both the untreated and treated copolymers
      induced only slight variations of platelet number, but determined the activated
      partial thromboplastin time (APTT) increase, due to factor XI reduction. Finally,
      a prototype of partially biodegradable vascular prosthesis was prepared with
      NaOH/HCl-treated copolymer. Pre-cultured HMVEC seeding of the prosthesis by means
      of a rotation device resulted in an almost completely coverage of the graft inner
      surface.

PMID- 14661880
TI  - A comparative study of chemical derivatisation methods for spatially
      differentiated cell adhesion on 2-dimensional microfabricated polymeric matrices.
AB  - This paper describes a study of surface derivatisation methods applied to two
      dimensional polymer matrices microfabricated using the Pressure-Assisted
      Microsyringe (PAM) technique. A blend of polylactide and polycaprolactone was
      used as the matrix material, and surface chemistry techniques based on silanes
      and polyethyleneglycol (PEG) derivatives were employed to render the surface
      underlying the scaffold anti-adhesive whilst polylysine was covalently coupled to
      the surface of the polymer matrix to enhance cell adhesion. Prior to cell
      adhesion tests, the surfaces and matrices were analysed using physico-chemical
      techniques, such as surface tension, surface potential and fluorescence. Adhesion
      of primary endothelial cells was evaluated using cell counting techniques. The
      results demonstrate that both PEGs and silanes are about 66% efficient at
      demarcating endothelial cell adhesion in short term experiments and that
      covalently-bound polylysine to the polymer matrix increases cell adhesion twofold
      with respect to the adsorbed polypeptide.

PMID- 14661881
TI  - A collagen-phosphophoryn sponge as a scaffold for bone tissue engineering.
AB  - Non-collagenous phosphoproteins that interact with a type-I collagen are thought
      to nucleate bone mineral into collagen networks of mineralized tissues.
      Previously, phosphophoryn cross-linked to type-I collagen was reported to be an
      effective nucleator of appatite. However, free phosphophoryn molecules inhibit
      the formation of apatite in vitro. On the basis of the above study, we expected a
      collagen-phosphophoryn sponge to be a good scaffold for bone-tissue engineering
      and examined the formation of bone in orthotopically transplanted composites of
      the sponge and bone marrow osteoblasts in vivo in Fischer rats. Osteoblastic
      primary cells were obtained from the bone shaft of femorae of Fisher rats,
      according to the method of Maniatopoulous et al. A suspension of marrow cells was
      distributed through a flask with standard culture medium and incubated at 37
      degrees C. When cultures were nearly confluent after 10 days, they were
      concentrated by centrifugation to 10(6) cells/ml and subcultured onto the
      synthesized collagen-phosphophoryn sponge and a collagen sponge (control). After
      14 days, the composites of collagen-phosphophoryn and osteoblastic cells as well
      as control composites were transplanted into bone-defect sites of Fisher rats
      (holes 2 mm in diameter) and then the wounds were sutured. The composites were
      harvested at 1-8 weeks after implantation, and stained with hematoxylin and
      eosin. It was found that more bone was formed in the composites of collagen
      phosphophoryn sponge and osteoblasts than control composites from 1 week to 8
      weeks, suggesting that the collagen-phosphophoryn sponge is a good candidate as a
      scaffold for bone-tissue engineering.

PMID- 14661882
TI  - Glial cell and fibroblast cytotoxicity study on 4026-cyclotene photosensitive
      benzocyclobutene (BCB) polymer films.
AB  - Photosensitive benzocyclobutene (photo-BCB) is a class of polymers with the trade
      name Cyclotene. The photoimagable property of Cyclotene makes it suitable for the
      manufacture of microelectronic devices. The motivation behind this study is that
      we see an exciting application of photo-BCB as substrates in implantable
      microelectronic biomedical devices due to several desirable properties
      distinctive from other polymer materials. To our knowledge, however, photo-BCB
      has never been tested for biomedical implant applications, as evidenced by the
      lack reported data on its biocompatibility. This study takes the first step
      towards assessing photo-BCB biocompatibility by evaluating the cytotoxicity and
      cell adhesion behavior of Cyclotene 4026 coatings exposed to monolayers of glial
      and fibroblast cells in vitro. It can be concluded from these studies that photo
      BCB films deposited on silicon wafers using microfabrication processes did not
      adversely affect 3T3 fibroblast and T98-G glial cell function in vitro. We also
      successfully rendered photo-BCB films non-adhesive (no significant fibroblast or
      glial cell adhesion) with surface immobilized dextran using methods developed for
      other biomaterials and applications. Future work will further develop prototype
      photo-BCB microelectrode devices for chronic neural implant applications.

PMID- 14661883
TI  - Compression-induced changes on physical structures and calcification of the
      aromatic polyether polyurethane composite.
AB  - It is generally accepted that stress causes calcification in both bio-prosthetic
      and polyurethane heart valves. However, simple uni-axially- and bi-axially
      stretched samples did not yield a feasible model for the elaboration of the
      stress-induced calcification. In this study, heat compaction combined with the
      incorporation of polyethylene has been explored. Specimens of polyurethane were
      solution cast onto a porous bi-axially-drawn ultra-high-molecular-weight
      polyethylene film and then heat compacted under a pressure of 18 MPa at a chosen
      temperature for 1.5 h. The heat-compaction-induced calcification and physical
      changes of the polyurethane composite were evaluated using a 28-day in vitro
      calcification model and Attenuated Total Reflection-Fourier Transform-Infrared
      (ATR-FT-IR) spectroscopy. The calcification results indicated that heat
      compaction-induced calcification was double that achieved without heat
      compaction. Heat-compacted polyurethane composite showed higher affinity to
      calcium ions than the non-heat compacted sample. The ATR-FT-IR results showed
      that the heat-compaction-induced physical changes include distortions of
      polymeric molecules and permanent changes of microstructures. The distortions of
      polymeric molecules could be deteriorated in contact with different media. The
      relaxation of the stressed structures of the polyether moiety might serve as a
      calcium trap and a heterogeneous nucleation site for calcification. The permanent
      changes of microstructures resulted from high distortions also served as affinity
      sites attracting calcification.

PMID- 14661884
TI  - Surface treatment of polycarbonate films aimed at biomedical application.
AB  - Aiming to encapsulate pancreatic islets, a biocompatible polycarbonate membrane
      (Whatman) was treated with plasma argon in order to improve its surface
      properties. The argon plasma treatment decreased the hydrophobicity of the
      membrane by fixing polyvinylpyrrolidone (PVP) at the surface. The water angle
      contact decreased from 47 degrees to 20 degrees after this treatment, while the
      structure and pore diameter were preserved. The treatment also increased
      significantly the water permeability from 62 +/- 8 ml/min to 200 +/- 29 ml/min (P
      < 0.001). ToF-SIMS analyses revealed that the argon plasma treatment of the
      membrane allowed the installation of an uniform PVP layer at the surface. The
      concentration equilibrum in glucose was reached after 8 h diffusion for the
      treated membrane, while it was only 32.4 +/- 8.6% (P < 0.01) for the untreated
      membrane. The biocompatibility of the polycarbonate membrane was assessed after
      one month of implantation in rats and proved to be unaffected by the surface
      treatment. In conclusion, the present study provided sufficient information to
      establish a relationship between the physicochemical modifications of the PVP
      plasma-treated polycarbonate membrane and the improvement in its permeability.

PMID- 14661886
TI  - New learning.

PMID- 14661885
TI  - Studies on nerve cell affinity of biodegradable modified chitosan films.
AB  - Chitosan, a natural polysaccharide that has excellent biocompatibility and
      biodegradability, can be used as nerve conduit material. The purpose of this work
      was to study the ability of chitosan and some chitosan-derived materials to
      facilitate nerve cell attachment, differentiation and growth. The biomaterials
      studied were chitosan, poly-L-lysine-blended chitosan (CP), collagen-blended
      chitosan (CC) and albumin-blended chitosan (CA), with collagen control material.
      Culture of PC12 cells and fetal mouse cerebral cortex (FMCC) cells on these
      biomaterials was used to evaluate their nerve cell affinity. The composite
      materials, including CP, CC and CA, had significantly improved nerve cell
      affinity compared to chitosan, as established by increasing attachment,
      differentiation and growth of PC12 cells. FMCC cells could also grow better on
      composite materials than on chitosan. CP exhibited the best nerve cell affinity
      among these three types of composite material. CP is an even better material in
      promoting neurite outgrowth than collagen, a substrate that is widely used in
      tissue engineering, suggesting that CP is a promising candidate material for
      nerve regeneration.

PMID- 14661887
TI  - Social and institutional feasibility of recycling nutrients in waste in Southern
      Thailand.
AB  - The social and institutional feasibility of recycling plant nutrients in waste in
      three case study areas, Phattalung, Kuan Lang and Prik, in Southern Thailand has
      been studied. Three sanitation systems (existing with modifications and
      alternative) in each area have been evaluated with respect to their acceptance
      among the local stakeholders and accommodation within the Thai legal framework.
      Culturally, most proposed recycling methods were accepted by local users, and
      great interest was expressed towards many of the proposed sanitation systems,
      except recycling methods involving direct contact with human excreta in Prik
      (Islamic culture). The three existing systems were assessed to be the most
      convenient and practical among the nine, due to their low maintenance requirement
      and the low user fees. The proposed modified and alternative sanitation systems
      involved higher public participation and thereby a change in the understanding of
      where the responsibility of managing people's waste products should be placed.
      Institutionally all nine sanitation systems were accepted by local administrators
      and all recycling systems were well accommodated within the Thai legal framework.
      Thus recycling plant nutrients in waste seem both social and institutionally
      acceptable in Southern Thailand.

PMID- 14661888
TI  - Intensive aerobic bioconversion of sewage sludge and food waste into fertiliser.
AB  - The aim of this research was to verify the possibility of recovering the
      nutrients present in sewage sludge and vegetable food waste as fertiliser after
      aerobic thermophilic intensive bioconversion. The process was performed in a
      closed reactor under controlled conditions of aeration, stirring and pH, at a
      temperature of 60 degrees C, after addition of a starter bacterial culture of
      Bacillus thermoamylovorans SW25. End product with the best fertilising properties
      was obtained when sewage sludge, mixed with food waste, CaCO3 and an artificial
      bulking agent was thermally pretreated. The content of volatile solids and
      organic carbon decreased from 82.8% to 62.3% and from 37.7% to 32.5% of total
      solids (TS) respectively, during 12 days of bioconversion. The stable organic
      fertiliser produced was a powder with moisture content of 5%. Furthermore, 3.4%
      of nitrogen, 0.4% of phosphorus and 2.9% of potassium were also present. Addition
      of 10-15g of this fertiliser to 1 kg of poor fertility soil increased the growth
      of different plants by 113-164%.

PMID- 14661889
TI  - Evaluation of pre-treatment methods for landfill disposal of residues from
      municipal solid waste incineration.
AB  - This study presents results concerning leaching of Pb, Cd, Ca, and Cl with
      reference to one individual batch of bottom ash and fly ash (5:1) resulting from
      a municipal solid waste incinerator (MSWI) in Japan. This ash mixture was
      stabilised by the following pre-treatments: water washing, carbonation, and
      phosphate stabilisation. Once the optimum processing condition for each pre
      treatment was determined, the performances were evaluated using both pH-stat
      leaching (pH 6, 9, 12) and availability tests. These performance tests were
      carried out with only fly ash without considering the mixture of MSWI residues,
      in order to accurately determine leaching differences among the pre-treatments.
      Water washing effectively removed the major elements from MSWI residues and also
      reduced the leachability of trace metals, such as Pb and Cd. A washing time of 15
      minutes with a liquid/solid ratio of 5 was reasonably effective. Carbonation had
      a significant effect on leachability in alkaline ranges (pH 9 and 12), when the
      reaction occurred only on the surface of MSWI residues, moreover a moisture
      content of 10-16.7% was proved suitable for carbonation. On the other hand,
      phosphate stabilisation, even with small amounts of phosphate (0.16 mol-PO4(3-)
      kg(-1)), was very effective in reducing the leachability of heavy metals.

PMID- 14661890
TI  - Design of a reverse osmosis plant for leachate treatment aiming for safe
      disposal.
AB  - Leachate treatment is one of the major environmental issues faced by landfill
      owners. One promising method for reduction of pollutant discharge is reverse
      osmosis (RO). RO technology was tested at a pilot plant at Hedeskoga Landfill in
      southern Sweden. This landfill receives municipal solid waste (MSW) and
      industrial, commercial and institutional (IC&I) waste, and produces about 3000
      m3/ha of leachate annually. Annual variations in the volume of leachate produced,
      estimated from changes in leachate electrical conductivity, were relatively small
      and should therefore have a minor effect on the main performance parameter of an
      RO plant, i.e., the achievable volume reduction. The volume reduction
      (V(permeate)/V(feed)) of polluted water achieved in batch experiments with 200
      1000 litres of raw leachate was more than 80% (4MPa) and the remaining 20% was
      left as retentate. However, raw leachate caused severe fouling problems in a
      continuous flow run and after 24 hours, the flux had decreased to about 20% of
      the initial value. By pre-treating the leachate in a storage pond combined with a
      wetland, the situation was significantly improved and the decrease in membrane
      flux was only 0.2% per hour during a 200 hour run. The retention in terms of
      total solids and chemical oxygen demand was 90%, and for ammonia, it was 82%, at
      a volume reduction of 50%. The HELP-model was used for prediction of the water
      balance for the Hedeskoga landfill, with special focus on estimation of potential
      evapotranspiration. With different types of vegetation and a volume reduction of
      75% in the RO plant, it was found possible to achieve safe disposal by irrigating
      25% to 40% of the leachate-producing landfill area with pre-treated leachate. Pre
      treatment with wetlands and nature based systems reduce the need of detergents
      for cleaning of the membranes and water only can be used. Short pre-treatment by
      aeration is not sufficient to bring leachate to a condition sustainable for RO
      treatment. In that case, it was found necessary with alkaline-acid-alkaline
      treatment to restore the permeability. The total treatment cost for a full scale
      treatment plant at Hedeskoga was estimated to be approximately 30 SEK/m3, of
      which 25 is capital and 5 is operational costs. This can be compared to the total
      treatment costs for municipal sewage in Sweden, which is 8 SEK/m3.

PMID- 14661891
TI  - Detection of gas leakage from landfills using infrared thermography-
      applicability and limitations.
AB  - Although landfill gas emission can be greatly reduced by extraction and
      converting gas to energy, in practice not all gas can be collected and some leaks
      can still occur. Management of landfill gas can be improved if leaks can be
      detected and rectified effectively. This paper provides a brief review of methods
      available for detecting landfill leakage, with a focus on infrared thermography.
      It then describes a study which was conducted to test if an infrared camera can
      be used to detect gas leaks accurately by identifying them as anomalies. It
      examined the applicability and limitations of the technique by investigating
      fundamental factors such as weather conditions, ground conditions and distance of
      sensor from source. The paper also describes a test case conducted to reinforce
      the findings. It concluded that unless all the fundamental factors are clearly
      understood and addressed, the technique currently can only be used as a screening
      tool rather than as a precise tool to detect landfill gas leakages. For this
      reason, it would be difficult to use the technique as a basis for modelling gas
      emission from landfills.

PMID- 14661892
TI  - Use of lignite fly ash as an additive in alkaline stabilisation and
      pasteurisation of wastewater sludge.
AB  - In this study, the possibility of using lignite fly ash in low doses for reducing
      the pathogen levels in wastewater sludge was investigated. The results showed
      that using fly ash alone in doses of 40%, 80% and 120% (on a dry weight basis),
      did not produce an alkaline environment for an efficient removal of pathogens.
      However, using fly ash in conjunction with the minimum amount of quicklime may
      act as an effective way of fecal coliform removal in both alkaline stabilisation
      and pasteurisation processes. It was shown that using fly ash in doses of 80% and
      120% in alkaline stabilisation and pasteurisation processes prevented the pH
      decays and regrowth of pathogens during 60 days of storage period. The results of
      the study confirmed that alkaline pasteurisation process produces a product which
      is more resistant to pH decays and regrowth of fecal coliforms compared to that
      of alkaline stabilisation. Consequently, the overall results of this study
      indicated that the minimum lime and fly ash dosages required to generate a Class
      B biosolid were 10-15% and 80%, respectively. On the other hand, heating sludge
      to 50 degrees C prior to the addition of 10-15% quicklime and 80% fly ash
      followed by further heating to 70 degrees C and then sustaining at this
      temperature for 30 minutes were sufficient to generate a Class A biosolid.

PMID- 14661893
TI  - Automobile shredder residue gasification.
AB  - Automobile Shredder Residue (ASR) shows a broad chemical composition owing to the
      presence of different materials, and its high organic content makes it
      interesting as a source of energy. In this work, a bench scale two-stage reactor
      is used for gasifying ASR. The reactor shows an efficient ASR gasification,
      avoiding the formation of difficult to manage char and tar and allowing an easy
      recovery of energy. The results of the investigation were used to test a simple
      model based on mass and energy balances and chemical equilibrium, predicting
      syngas composition including the presence of problematic elements such as sulphur
      and chlorine. Gasification data calculated by the model agree in a satisfactory
      way with the experimental ones. Due to the large variation in ASR composition,
      the model predicts that ASR gasification is industrially feasible only if a blend
      of ASR and RDF is used as a reactor feed.

PMID- 14661894
TI  - Spent potlining utilisation possibilities.
AB  - As the world's capacity for aluminium production increases, the amount of waste
      connected with this industry is also increasing. Spent potlining (SPL) from
      aluminium reduction cell cathodes presents a major environmental concern in the
      primary aluminium industry. It is concluded, after laboratory tests, that
      leachable cyanide and fluoride compounds present the major problem in SPL
      disposal. The behaviour of cyanide and fluoride under high temperature treatment
      has been investigated. On the basis of this laboratory investigation, the
      possibilities for SPL utilisation in red brick manufacturing, cement industry and
      thermal power stations were evaluated. SPL refractory material is already re-used
      in red brick manufacturing. In the cement industry, a pilot test on the
      utilisation of 25 t SPL carbon waste mixed with green petrol coke gave positive
      results. Additionally a fluoride emission forecast for a thermal power station
      utilising carbon waste SPL mixed with coal was elaborated.

PMID- 14661895
TI  - Report: pipeline transport of solid waste in the Grand Holy Mosque in Makkah.
AB  - The Grand Holy Mosque, located in the Holy City of Makkah in Saudi Arabia,
      attracts millions of Muslim visitors from all over the world, especially during
      the pilgrimage season. The daily amount of refuse generated in the Grand Holy
      Mosque and surrounding plazas reached a maximum value of 192.8 tons/day in 1998.
      Collection and transport of the solid waste generated during the peak times
      present a challenge to the Makkan authorities. The congested streets and high
      population density in the Holy Mosque and its surrounding plazas make the
      traditional methods of collecting and transporting solid waste impractical. This
      paper presents an alternative system for the collection and transport of solid
      waste generated in and around the Grand Holy Mosque in Makkah. The proposed
      system is based on a pneumatic transport technique, by which the waste is
      collected and transported in underground pipelines. A conceptual layout of the
      proposed system in the Mosque area is presented, and the merits of the suggested
      system are discussed.

PMID- 14661896
TI  - Report: cost and financing of municipal solid waste collection services in
      Istanbul.
AB  - The collection is a high priority in the management of solid wastes in a modern
      city, and in order to plan and operate a collection service well, the cost and
      financial sources must be known and understood in detail. In this study the cost
      of collection services and environmental tax are evaluated for the year 2001 in
      Istanbul. The percentage of the employees working in municipal solid waste
      collection services is 83% by the private sector and 17% by the public sector.
      With privatisation, the labour costs can be reduced by approximately 75%. The
      unit collection cost ranges from 12.2 US dollar/ton to 50.7 US dollar/ton, and
      the average collection cost for Istanbul is 24.4 US dollar/ton. The cost of the
      collection service is about 70% of the total solid waste management costs, the
      cost of transfer is 17% and the regular disposal cost amounts to 13%. The
      proportion of collected tax to expenditures of waste collection varies from 3% to
      67%. The management of solid wastes accounts for between 12 and 25% of the total
      expenditure of municipal authorities.

PMID- 14661897
TI  - Effects of octreotide acetate and amniotic membrane on wound healing in
      experimental glaucoma surgery.
AB  - Wound healing affects the success of glaucoma filtering surgery. Antimetabolites
      and antifibrotic agents are used in the modulation of surgical trauma. This study
      is performed to evaluate the effects of amniotic membrane and octreotide acetate
      on wound healing. Thirty pigmented rabbits were divided into three groups each
      including 10 animals. Trabeculectomy and topical postoperative prednisolone
      sodium phosphate four times daily for 7 days were applied to one eye of all the
      rabbits. After trabeculectomy, octreotide 10 microg three times daily applied
      topically to the octreotide group for 14 days and amniotic membrane
      transplantation was performed by suturing amniotic membrane between scleral flap
      and sclera to the amniotic membrane group. The operated eyes of the rabbits were
      enucleated on the 14th day of the operation and histopathological specimens were
      obtained from the bleb sites and they were evaluated by light microscope.
      Fibroblast and macrophage number per cm2 were counted and the average values were
      calculated. Compared with the control group, the fibroblasts and macrophages
      significantly decreased in the other two groups (p < 0.0001, p < 0.0001,
      respectively). The mean number of fibroblasts was lower than those of the control
      and amniotic membrane groups (p < 0.0001, p < 0.0001, respectively). Similarly
      the mean macrophage number was significantly lower in the octreotide group versus
      the control and amniotic membrane groups (p < 0.0001, p < 0.01, respectively).
      Octreotide administration and amniotic membrane transplantation might be
      alternative treatments in modulating the wound healing after trabeculectomy.

PMID- 14661898
TI  - Correlation between frequency doubling technology perimetry and temporal
      frequency characteristics in early glaucoma.
AB  - To assess the effectiveness of the temporal frequency characteristics (TFC) as an
      indicator of visual damage in patients with early open-angle glaucoma, TFC
      obtained from VEPs elicited by a pseudorandom binary sequence (PRBS) stimulus was
      compared with the frequency doubling technology (FDT) thresholds. Cross power
      spectrum between the PRBS stimulus as the input and the PRBS-VEPs as the output
      was calculated, and was used as the TFC. The normalized amplitude of the TFC at 2
      4, 6-8, 10-12, 14-16, 18-20, 22-24, 26-28, and 30-32 Hz was calculated, and a
      coefficient of correlation between these values and the FDT thresholds was
      determined. The coefficients of correlation between the FDT thresholds and the
      TFC at 18-20 Hz for the central, 10 degrees, 20 degrees, and 30 degrees were r =
      0.03, 0.31, 0.21, and 0.16, respectively in non-glaucomatous normal control eyes,
      and those for the same regions of eyes with early glaucoma were r = 0.66, 0.46,
      0.38, and 0.35, respectively. The coefficients of correlation between the FDT
      thresholds and TFC at temporal frequencies were relatively high at 18-20 and 26
      32 Hz. The time required to obtain the PRBS-VEP data was approximately the same
      as that for the FDT thresholds. The strong correlation between the two tests
      indicates that the FDT values and the high temporal frequency segments of the TFC
      may be useful as a preliminary indicator of visual damage in patients with early
      open-angle glaucoma. In addition, the strong correlation suggests that there was
      a preferential damage to the magnocellular system in glaucomatous eyes.

PMID- 14661899
TI  - Impairment of optic path due to radiotherapy for nasopharyngeal carcinoma.
AB  - PURPOSE: To evaluate the impairment of optic path caused by radiotherapy for
      nasopharyngeal carcinoma (NPC). METHODS: Visual evoked potential was used to
      evaluate the functional impairment of optic path by an 8 MV linear accelerator or
      60Co gamma-ray radiotherapy in 63 (23 women and 40 men) patients with
      nasopharyngeal carcinoma before radiotherapy, at the end of radiotherapy, 6
      months and 1, 2 and 3 years after their radiotherapy respectively. RESULTS: In
      the female group, the latency of VEP elicited by the three types of elements
      significantly delayed 2 and 3 years after radiotherapy than that before
      radiotherapy, at the end of radiotherapy, 6 months and 1 year after radiotherapy;
      there were no significant difference among VEP amplitudes elicited by the three
      types of elements before and after radiotherapy. In the male group, the latency
      of VEP elicited by the medium and the small elements significantly delayed 1 year
      after radiotherapy than that before radiotherapy and at the end of radiotherapy,
      the VEP latency elicited by the small elements was significantly prolonged 3
      years after radiotherapy compared to that just after radiotherapy, while the VEP
      amplitude elicited by the large elements was significantly attenuated 1 year
      after radiotherapy compared to those before and just after radiotherapy.
      CONCLUSIONS: In the female group, the significant prolongation of VEP latency
      happened at the end of radiotherapy and lasted for 3 years, while the VEP
      amplitude did not change significantly during the 3 years after radiotherapy. It
      indicates that the sustained impairment by radiation within the female visual
      nerve system starts at the end of radiotherapy, but the impairment was mild. In
      the male group, the significant prolongation of VEP latency mostly happened 1 or
      2 years after radiotherapy. It was shown that the radiotherapy for nasopharyngeal
      carcinoma certainly injured the optic path, and there was difference in the
      impairment between the two sexes.

PMID- 14661900
TI  - Acute electroretinographic changes during sildenafil (Viagra) treatment for
      erectile dysfunction.
AB  - The authors describe their findings on 12 subjects who were treated with 50 mg of
      sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after
      ingestion. The Naka-Rushton equation was used to describe the b-wave luminance
      response function of the scotopic ERG. Statistically significant differences were
      noted in the Vmax and K values. Sildenafil ingestion resulted in an increase in
      Vmax (higher rod response to light stimuli) and a decrease in K (higher
      sensitivity).

PMID- 14661901
TI  - Relationship between motion VEP and perceived velocity of gratings: effects of
      stimulus speed and motion adaptation.
AB  - The N200 amplitude of the motion-onset VEP evoked by a parafoveal grating of
      variable speed (0.25-13.5 degrees/s), constant spatial frequency (2 cpd),
      contrast (4%), and direction (horizontally rightward) was studied before and
      after adaptation to a stationary or drifting grating (1 or 4 degrees/s).
      Psychophysical measurements were made simultaneously of the perceived speed. In
      the unadapted condition the slope of the N200 amplitude versus speed function is
      positive, but lower for high compared to low speeds. The N200 amplitude increases
      slightly after stationary adaptation. An increase in perceived speed is also
      evident after stationary adaptation. This increase is more pronounced for low
      compared to high speeds. Motion adaptation reduces N200 amplitudes over the
      entire speed range, whereas perceived speeds change from under-estimation to over
      estimation when the speed exceeds 1.8 degrees/s after 1 degree/s adaptation and
      4.5 degrees/s after 4 degrees/s adaptation. The simultaneous evaluation of motion
      VEP and psychophysical results supports the view that the neurons generating the
      N200 component are also involved in speed perception. The data suggest the
      existence of a limited number (three or more) speed channels.

PMID- 14661902
TI  - Visual field defects in pediatric patients on vigabatrin monotherapy.
AB  - Vigabatrin (GVG) is an effective antiepileptic drug used for treating partial
      seizures in adults and children. Over the last years, an increasing number of
      articles have been published reporting visual field defects (VFD) associated with
      GVG therapy in adults. To date, however, only an small number of pediatric
      patients have been reported. This paper is a retrospective review of clinical
      review to evaluate the prevalence and features of VFD in pediatric patients on
      GVG monotherapy. METHODS: Fifteen children, on GVG therapy in the Department of
      Child Neurology, underwent visual field examination by static threshold automated
      perimetry using the Humphrey Field Analyzer Program 30-2. The age of these
      patients ranged from 6 to 18 years (12.4 +/- 3.6 years), 10 of them being male
      and five female. RESULTS: Three patients (20%) on GVG monotherapy showed VFD.
      These consisted in localised, bilateral, and relatively symmetrical, nasal field
      loss, with relative preservation of the temporal field within the central 30
      degree area.

PMID- 14661903
TI  - Eye movement baseline oscillation and variability of eye position during
      foveation in congenital nystagmus.
AB  - Despite the inability to maintain steady fixation, congenital nystagmus does not
      necessarily reduce visual acuity, that can be achieved during the foveation
      periods. The duration of the foveation period, but also the cycle-to-cycle
      variability of eye position and velocity during foveations play an important
      role. A quantitative relationship that relates visual acuity with foveation time
      and cycle-to-cycle variability of eye position during foveation has been
      previously proposed. In many infrared-oculographic and electro-oculographic eye
      position recordings of our database, a sinusoidal-like oscillation of the
      baseline was observed, on which the nystagmus waveforms lay. This oscillation may
      contribute to increase cycle-to-cycle variability during foveations. The aim of
      this work is to extract the baseline oscillation from the recordings and to
      verify its relationship with eye position variability during foveation. On the
      basis of the observations, the baseline oscillation was assumed to be sinusoidal,
      and was estimated (using a least mean square technique) from eye movement signals
      recorded during fixation intervals, at different gaze positions, from 20 patients
      affected by congenital nystagmus with low visual acuity. The average baseline
      oscillation amplitude was 1.31 degrees, while the average frequency was 0.34 Hz.
      Baseline oscillation amplitude was well correlated (with a coefficient of 0.66)
      to the standard deviations of eye-position during foveation, which in turn is
      connected to visual acuity.

PMID- 14661904
TI  - Characteristics of braking saccades in congenital nystagmus.
AB  - Several of the characteristic waveforms of congenital nystagmus (CN) contain
      braking saccades. We test the hypothesis that braking (including foveating)
      saccades, while not always satisfying the standard relationships for saccades,
      are normal; any differences are due to the presence of high-velocity, slow-phase
      eye movements. Better measurements of saccadic properties, including position-
      and velocity-based measures and skewness, can eliminate some of this apparent
      distortion. We also evoked an analogous effect in normal subjects by use of a
      ramp-step-ramp stimulus. Finally, we used a model to further demonstrate this
      distortion in the saccades of normals, deviating from their intended magnitude as
      a function of the magnitude of the opposing velocity. The saccadic analysis
      methods developed herein are applicable to all saccades made during ongoing eye
      movements, whether normal or pathological. The above findings support the
      hypothesis that the braking saccades integral to many CN waveforms have normal
      characteristics and are the result of a normal saccadic system's responses to a
      slow-eye-movement oscillation.

PMID- 14661905
TI  - Abnormalities of the scotopic threshold response correlated with gene mutation in
      X-linked retinoschisis and congenital stationary night blindness.
AB  - STRs and dark-adapted ERGs were recorded in nine normal subjects, nine patients
      with XLRS, 11 patients with CSNB1 and one patient with CSNB2. In XLRS STR
      amplitude was significantly lower than normal at every intensity, but the
      response could be recorded in every patient and the maximum amplitude response
      was outside the 95% confidence limits in only four of the nine patients. STRs
      were significantly poorer in patients with CSNB and a responses was not
      measurable at any intensity in nine of the 11 patients with CSNB1. In both CSNB
      and XLRS the STR could only be recorded at higher stimulus intensities,
      suggesting reduced sensitivity of the STR. In XLRS onset and peak latencies were
      also significantly prolonged and the slope of the intensity-response functions
      for amplitude and onset latency differed significantly from normal. Maximum STR
      amplitude did not correlate with the maximum dark-adapted ERG response. The
      finding of abnormal STRs and dark adapted ERGs in all three dystrophies indicates
      that the different causative genes must have similar effects on the rod On
      bipolar cell pathway. But there were also differences between the three clinical
      groups, particularly in the greater severity of the abnormality in CSNB1, which
      suggests that there may be multiple sites of abnormality.

PMID- 14661906
TI  - The changes of multifocal electroretinography in the early stage of photodynamic
      therapy for choroidal neovascularization.
AB  - To investigate short-term changes in the multifocal electroretinography (ERG)
      recordings after photodynamic therapy (PDT) for choroidal neovascularization
      (CNV), 16 patients (17 eyes) with classic CNV confirmed by fluorescein
      angiography (FA) and indocyanine green angiography (ICGA), including 11 cases (12
      eyes) of exudative age-related macular degeneration (AMD), two cases (two eyes)
      of pathological myopia and three cases (three eyes) of idiopathic causes, were
      treated using PDT with verteporfin. The multifocal ERGs of these patients were
      tested with VERIS Science 4.0 imaging system. The latencies and average response
      densities of all six ring retinal regions were measured and compared before PDT
      and 3 or 7 days after PDT. The latencies and amplitude densities of the N1 and P1
      waves in all six rings remained unchanged at 3 or 7 days post-treatment (p >
      0.05). Therefore, there is no significant evidence to suggest an adverse effect
      from PDT for classic CNV on the outer retinal function in the early stage of
      treatment, with the aid of the multifocal ERG recordings.

PMID- 14661907
TI  - Safety and efficacy evaluation of a new electrode (the LVP electrode) part I.
      Pattern ERG pilot study.
AB  - We have designed a less expensive, non-corneal ERG electrode. Named as the LVP
      electrode, this new disposable electrode was found safe and reliable for pattern
      ERG recordings.

PMID- 14661908
TI  - Safety and efficacy evaluation of a new ERG electrode (the LVP electrode) part
      II. Flash ERG pilot study.
AB  - A new disposable, non-contact electrode (LVP electrode) was evaluated for use in
      recording flash ERG. A comparison of DTL and LVP electrodes showed reproducible
      waveforms for all components analysed. There was a good correlation obtained
      between the DTL and LVP electrodes. The LVP electrode is safe, less expensive and
      has less movement of the fiber due to its rigidity.

PMID- 14661909
TI  - Guidelines for calibration of stimulus and recording parameters used in clinical
      electrophysiology of vision.

PMID- 14661910
TI  - Influence of axial length of normal eyes on PERG.
AB  - The influence of the axial length (AL) of the eye on flash electroretinogram
      (ERG) responses has been well established in the literature, suggesting an
      association between ERG abnormalities with myopia (AL > 25 mm). The aim of our
      present study was to determine whether the AL of normal eyes can also influence
      the pattern electroretinogram (PERG) on normal subjects. Thirty-nine normal
      volunteers were subjected to PERG measurements following the standard set by the
      International Society for Clinical Electrophysiology of Vision (ISCEV). The AL of
      the eyeball was measured using a TOMEY ultrasonic A scanner. Each volunteer had a
      complete ophthalmic examination including visual acuity, refraction, intraocular
      pressure, visual field, colour vision, orthoptic assessment and retinal
      photographs and had a best corrected visual acuity of 6/9 or better. Only one eye
      from each of the 39 normal volunteers was included in the statistical analysis of
      the results. The normal volunteer group had a mean P50 amplitude of 3.8 +/- 1.1
      SD microV. The range of AL was between 21.8 and 25.7 mm (mean = 23.8 +/- 1.0 SD
      mm). Overall findings obtained from this investigation indicate a significant
      correlation between the AL of normal eyes and the PERG P50 amplitude (Spearman
      rank correlation coefficient r = -0.413, p < 0.01). The correlation accounts for
      17% of the variance observed in the 39 amplitude values. This confirms the
      current hypothesis that the PERG amplitude is inversely related to axial length
      and means that AL should be considered when interpreting PERG amplitudes.

PMID- 14661911
TI  - Abnormal flash but normal pattern VEP in a cavernous sinus meningioma.

PMID- 14661912
TI  - ERGs in female carriers of incomplete congenital stationary night blindness (I
      CSNB). A family report.
AB  - ERG findings in five sisters are reported. By pedigree analysis, four of the five
      must be obligate carriers for I-CSNB since their sons were affected (impaired
      night vision, reduced visual acuity, variable ametropia, congenital nystagmus and
      ERG with both scotopic and photopic b-wave reduced amplitude). The fifth was
      childless at the time of examination and her ERG analysis was normal. Three of
      the four obligate carriers showed significant reduction in the sum of the OPs
      amplitude as previously reported as being an electrophysiological signs in female
      carriers: two without alteration in other ERG components and the third with
      association with a flicker ERG amplitude significantly increased. The fourth
      female carrier showed a normal sum of the OPs amplitude whereas the other b-wave
      ERG or flicker amplitudes were significantly decreased. These last two ERG
      results suggest a possible modifications of synaptic transmission at a post
      receptoral site (outer plexiform layer or involvement of the bipolar pathways) in
      these two carriers.

PMID- 14661913
TI  - High-throughput proteomic-based identification of oxidatively induced protein
      carbonylation in mouse brain.
AB  - PURPOSE: The major initiative of this study was to implement a novel proteomic
      approach in order to detect protein carbonylation in aged mouse brain. Several
      lines of evidence indicate that reactive oxygen species (ROS)-induced protein
      oxidation plays an essential role in the initiation of age-related
      neuropathologies. Therefore, the identification of free radical or peroxide
      substrates would provide further insight into key biochemical mechanisms that
      contribute to the progression of certain neurological disorders. METHODS:
      Historically, ROS targets have been identified by conventional immunological two
      dimensional (2-D) gel electrophoresis and mass spectrometric analyses. However,
      specific classes of proteins, such as transmembrane-spanning proteins, high
      molecular-weight proteins, and very acidic or basic proteins, are frequently
      excluded or underrepresented by these analyses. In order to fill this technologic
      gap, we have used a functional proteomics approach using a liquid chromatography
      tandem mass spectrometric (LC-MS/MS) analysis coupled with a hydrazide biotin
      streptavidin methodology in order to identify protein carbonylation in aged mice.
      RESULTS: Our initial studies suggest an ability to identify at least 100
      carbonylated proteins in a single LC-MS/MS experiment. In addition to high
      abundance cytosolic proteins that have been previously identified by 2-D gel
      electrophoresis and mass spectrometric analyses, we are able to identify several
      low-abundance receptor proteins, mitochondrial proteins involved in glucose and
      energy metabolism, as well as a series of receptors and tyrosine phosphatases
      known to be associated with insulin and insulin-like growth factor metabolism and
      cell-signaling pathways. CONCLUSIONS: Here we describe a rapid and sensitive
      proteomic analysis for the identification of carbonylated proteins in mouse brain
      homogenates through the conjunction of liquid chromatography and tandem mass
      spectrometry methods. We believe the ability to detect these post-translationally
      modified proteins specifically associated with brain impairments during the
      course of aging should allow one to more closely and objectively monitor the
      efficacy of various clinical treatments. In addition, the discovery of these
      unique brain biomarkers could also provide a conceptual framework for the future
      design of alternative drugs in the treatment of a variety of age-related
      neurodegenerative disorders.

PMID- 14661914
TI  - Temperature- and pH-induced multiple partially unfolded states of recombinant
      human interferon-alpha2a: possible implications in protein stability.
AB  - PURPOSE: To study the effect of solution conditions on the structural
      conformation of recombinant human interferon-alpha2a (IFNalpha2a) to investigate
      its tendency to form partially unfolded intermediates. METHODS: The structural
      properties of IFNalpha2a were studied at various pH values (2.0-7.4) and
      temperatures (5 degrees C-80 degrees C) using Trp fluorescence emission,
      fluorescence quenching, near- and far-UV circular dichroism (CD) spectroscopy,
      and DSC. RESULTS: Fluorescence intensity measurements as a function of
      temperature indicated the onset of the thermal unfolding of IFNalpha2a, denoted
      by Td, around 60 degrees C above pH 4.0. Td was not observed at pH 3.5 and below.
      Acrylamide and iodide quenching studies indicated partial unfolding of protein
      with decrease in pH and with increase in temperature up to 50 degrees C. Near-UV
      CD studies indicated a significant loss in the tertiary structure of protein on
      increase in temperature from 15 degrees C to 50 degrees C at all solution pHs.
      DSC scans supported results obtained from fluorescence and CD studies at pH 4.0
      and below. DSC, however, was insensitive to changes that occurred at moderate
      temperatures at pH 5.0 and 7.4. CONCLUSIONS: IFNalpha2a has a tendency to acquire
      multiple partially unfolded states with structural conformations sensitive to
      solution pH and temperature. These states were formed at moderate temperatures,
      and it is speculated that these partially unfolded states could play an important
      role in the aggregation of proteins during the long-term storage of aqueous
      protein formulations.

PMID- 14661915
TI  - Gene delivery in tissue engineering: a photopolymer platform to coencapsulate
      cells and plasmid DNA.
AB  - PURPOSE: Toward the ultimate goal of developing an engineered tissue capable of
      mimicking complex natural healing processes, we have designed a photopolymer
      platform that enables simultaneous encapsulation of cells and plasmid DNA in
      degradable hydrogels. Photopolymerization enables spatial and temporal control of
      gel formation under physiological conditions, but the presence of photoinitiator
      radicals poses challenges for DNA photoencapsulation. METHODS: The effects of
      photoinitiating conditions (ultraviolet light and photoinitiator radicals) on
      plasmid DNA were studied. Protection methods were identified. Plasmid DNA was
      photoencapsulated in photocrosslinked hydrogels, and the quantity and quality of
      the released DNA were assessed. Plasmid DNA was simultaneously entrapped
      (coencapsulated) with cells in hydrogels to assess in situ transfection. RESULTS:
      Experiments showed that in the absence of other species, plasmid DNA was
      sensitive to photoinitiator radicals, but the addition of transfection agents
      and/or antioxidants greatly reduced DNA damage by radicals. Encapsulated plasmid
      DNA was released from degradable, photocrosslinked hydrogels in active forms
      (supercoiled and relaxed plasmids) with an overall -60% recovery. Released DNA
      was capable of transfecting both plated and encapsulated cells. Encapsulated
      cells expressed the encoded gene of the coencapsulated plasmid as the polymer
      degraded. CONCLUSIONS: This photopolymerization platform allows for the creation
      of engineered tissues with enhanced control of cell behavior through the
      spatially and temporally controlled release of plasmid DNA.

PMID- 14661916
TI  - A fluorescent hPept1 transporter substrate for uptake screening.
AB  - PURPOSE: To synthesize fluorescent analogues of hPept1 substrates, FITC-Val-OCH3,
      Lys-FITC-OH, and Lys-FITC-OCH3, and to characterize their hPept1 transporter
      mediated uptake. METHODS: FITC analogues of amino acids were synthesized using
      established synthetic procedures, and the extent of their [3H]Gly-Sar uptake
      inhibition in HeLa/hPept1 cells was determined. The uptake of Lys-FITC-OCH3 was
      evaluated in HeLa, HeLa/hPept1, and Caco-2 cells in the presence and absence of
      Gly-Sar using a fluorescence microscopy-based assay. The uptake and transport of
      the Lys-FITC analogues were also determined in Caco-2 cells using HPLC assays.
      RESULTS: In HeLa/hPept1 cells, [3H]Gly-Sar uptake was significantly inhibited by
      Lys-FITC-OCH3 (74%) but not by FITC-Val-OCH3 (22%). The uptake of Lys-FITC-OCH3
      (100 microM) was approximately 10-fold higher in HeLa/hPept1 cells. Also, Lys
      FITC-OCH3 (100 microM) uptake in HeLa/hPept1 and Caco-2 cells was reduced by 77%
      and 80%, respectively, in the presence of 1 mM Gly-Sar. Dipeptides and cephalexin
      significantly reduced Lys-FITC-OCH3 uptake in Caco-2 cells. The apical
      permeability of Lys-FITC-OCH3 (1.5 x 10(6) cm/s) in Caco-2 cells was
      significantly lowered in the presence of Gly-Sar. Fluorescence micrographs
      revealed that this analogue was localized in the cytoplasm and in the nucleus.
      CONCLUSIONS: The combined results indicate that Lys-FITC-OCH3 is recognized and
      transported by hPept1 in HeLa/hPept1 and by peptide transporters in Caco-2 cells.
      The results also suggest that Lys-FITC-OCH3 might be a useful fluorescent
      substrate for rapid assessment of peptide transporter activity in cells of
      interest.

PMID- 14661917
TI  - Casein enhances stability of peptides in intestinal lumen: role of digested
      products of casein.
AB  - PURPOSE: To investigate the inhibitory activity of casein on proteases in detail,
      the effect of digested products of casein itself on trypsin and chymotrypsin in
      rat small intestine was examined. METHODS: Male Sprague-Dawley rats weighing 200
      300 g were used as the animal model. The luminal content of the jejunum was
      prepared, and the enzymatic activities of trypsin and chymotrypsin were
      determined using a specific substrate for each protease. Then, the effect of
      enzymatic digested products of casein on them was examined. RESULTS: The
      inhibitory activity of trypsin-digested casein against trypsin decreased as its
      digestion proceeded, but its inhibitory activity against chymotrypsin came to be
      more effective. On the other hand, the inhibitory activity of chymotrypsin
      digested casein against chymotrypsin decreased with the degree of digestion, but
      no change in the inhibitory activity against trypsin was observed. Even the
      completely digested products of casein with trypsin or chymotrypsin showed
      inhibitory activities against the two proteases. CONCLUSIONS: It was suggested
      that not only the intact casein but also the products digested with trypsin or
      chymotrypsin contribute to the inhibitory effect of casein on the proteases in
      the intestinal lumen.

PMID- 14661918
TI  - The use of clinical trial simulation to support dose selection: application to
      development of a new treatment for chronic neuropathic pain.
AB  - PURPOSE: Pregabalin is being evaluated for the treatment of neuropathic pain. Two
      phase 2 studies were simulated to determine how precisely the dose that caused a
      one-point reduction in the pain score could be estimated. The likelihood of
      demonstrating at least a one-point change for each available dose strength was
      also calculated. METHODS: A pharmacokinetic-pharmacodynamic (PK/PD) model
      relating pain relief to gabapentin plasma concentrations was derived from a phase
      3 study. The PK component of the model was modified to reflect pregabalin PK. The
      PD component was modified by scaling the gabapentin concentration-effect
      relationship to reflect pregabalin potency, which was based on preclincal data.
      Uncertainty about the potency difference and the steepness of the concentration
      response slope necessitated simulating a distribution of outcomes for a series of
      PK/PD models. RESULTS: Analysis of the simulated data suggested that after
      accounting for the uncertainty, there was an 80% chance that the dose defining
      the clinical feature was within 45% of the true value. The likelihood of
      estimating a dose that was within an acceptable predefined precision range
      relative to a known value approximated 60%. The minimum dose that should be
      studied to have a reasonable chance of estimating the dose that caused a one
      point change was 300 mg. CONCLUSIONS: Doses that identify predefined response may
      be imprecisely estimated, suggesting that replication of a similar outcome may be
      elusive in a confirmatory study. Quantification of this precision provides a
      rationale for phase 2 trial design and dose selection for confirmatory studies.

PMID- 14661919
TI  - Prediction of a stable microemulsion formulation for the oral delivery of a
      combination of antitubercular drugs using ANN methodology.
AB  - PURPOSE: The aim of this project was to develop a colloidal dosage form for the
      oral delivery of rifampicin and isoniazid in combination with the aid of
      artificial neural network (ANN) data modeling. METHODS: Data from the 20
      pseudoternary phase triangles containing miglyol 812 as the oil component and a
      mixture of surfactants or a surfactant/cosurfactant blend were used to train,
      test, and validate the ANN model. The weight ratios of individual components were
      correlated with the observed phase behavior using radial basis function (RBF)
      network architecture. The criterion for judging the best model was the percentage
      success of the model prediction. RESULTS: The best model successfully predicted
      the microemulsion region as well as the coarse emulsion region but failed to
      predict the multiphase liquid crystalline phase for cosurfactant-free systems
      indicating the difference in microemulsion behavior on dilution with water.
      CONCLUSIONS: A novel microemulsion formulation capable of delivering rifampicin
      and isoniazid in combination was created to allow for their differences in
      solubility and potential for chemical reaction. The developed model allowed
      better understanding of the process of microemulsion formation and stability
      within pseudoternary colloidal systems.

PMID- 14661920
TI  - A physiologic model for simulating gastrointestinal flow and drug absorption in
      rats.
AB  - PURPOSE: The development of a physiologically based absorption model for orally
      administered drugs in rats is described. METHODS: Unlike other models that use a
      multicompartmental approach, the GI tract is modeled as a continuous tube with
      spatially varying properties. The mass transport through the intestinal lumen is
      described via an intestinal transit function. The only substance-specific input
      parameters of the model are the intestinal permeability coefficient and the
      solubility in the intestinal fluid. With this physiologic and physicochemical
      information, the complete temporal and spatial absorption profile can be
      calculated. RESULTS: A first performance test using portal concentration data
      published in the literature yielded an excellent agreement between measured and
      simulated temporal absorption profiles in the portal vein. Furthermore, the dose
      dependence of a compound with solubility-limited fraction dose absorbed in rats
      (chlorothiazide) could be adequately described by the model. CONCLUSIONS: The
      continuous absorption model is well suited to simulate drug flow and absorption
      in the GI tract of rats.

PMID- 14661921
TI  - In situ blood-brain barrier transport of nanoparticles.
AB  - PURPOSE: Two novel types of nanoparticles were evaluated as poten tial carriers
      for drugs across the blood-brain barrier (BBB). METHODS: Nanoparticles were
      composed of biocompatible materials including emulsifying wax (E. Wax) or Brij
      72. Brij 78 and Tween 80 were used as surfactants for E. Wax nanoparticles (E78
      NPs) and Brij 72 nanoparticles (E72 NPs), respectively. Both nanoparticle
      formulations were prepared from warm microemulsion precursors usin melted E. Wax
      or Brij 72 as the oil phase. Nanoparticles were radio-labeled by entrapment of
      [3H]cetyl alcohol, and entrapment efficiency and release of radiolabel were
      evaluated. The transport of E78 and E72 NPs across the BBB was measured by an in
      situ rat brai perfusion method. RESULTS: Both formulations were successfully
      radiolabeled by entrapment of [3H]cetyl alcohol; -98% of radiolabel remained
      associated with nanoparticles at experimental conditions. The transfer rate (Kin)
      of E78 NPs from perfusion fluid into the brain was 4.1 +/- 0.5 x 10(-3) ml/s/g,
      and the permeability-surface area product (PA) was 4.3 +/- 0.7 x 10(-3) ml/s/g.
      The values for Kin and PA for E72 NPs were 5.7 +/- 1.1 x 10(-3) ml/s/g and 6.1 +/
      1.4 x 10(-3) ml/s/g, respectively. CONCLUSIONS: For both nanoparticle types,
      statistically significant uptake was observed compared to [14C]sucrose,
      suggesting central nervous system uptake of nanoparticles. The mechanism
      underlying th nanoparticle brain uptake has yet to be fully understood.

PMID- 14661922
TI  - Absence of toxicity of chronic weekly intravenous gene therapy with pegylated
      immunoliposomes.
AB  - PURPOSE: Plasmid DNA-based gene therapy involves episomal gene expression and
      must be given on a chronic basis. Therefore, the purpose of the present study was
      to examine for toxic side effects of the chronic weekly intravenous
      administration of plasmid DNA delivered with a nonviral gene transfer method
      using pegylated immunoliposomes (PIL). METHODS: A 7-kb expression plasmid
      encoding for rat tyrosine hydroxylase (TH) was encapsulated in PILs targeted with
      either the murine OX26 monoclonal antibody (MAb) to the rat transferrin receptor
      (TfR) or with the mouse IgG2a isotype control antibody. Rats were treated with
      weekly intravenous injections of 5 microg/rat/week of the TH expression plasmid
      DNA encapsulated in either the TfRMAb-targeted PIL or the mouse IgG2a-targeted
      PIL for a total period of 6 weeks. A third control group of rats was treated with
      saline. RESULTS: The animals treated with either saline, the TfRMAb-PIL, or the
      mouse IgG2a-PIL had no measurable differences with respect to body weights, 14
      serum chemistries, or organ histology of brain, liver, spleen, kidney, heart, or
      lung. Immunocytochemistry showed no evidence of inflammation in brain. The
      delivery to brain of the TH expression plasmid was confirmed with Southern
      blotting. CONCLUSIONS: The PIL nonviral gene transfer method causes no toxic side
      effects following chronic weekly intravenous administration in rats.

PMID- 14661923
TI  - Novel polysaccharide-decorated poly(isobutyl cyanoacrylate) nanoparticles.
AB  - PURPOSE: The aim of this work was to synthesize new surface-modified
      nanoparticles using a radical emulsion polymerization of an alkyl cyanoacrylate.
      METHODS: Isobutyl cyanoacrylate was polymerized in nitric acid 0.2 M containing a
      polysaccharide (0.1375 g) and cerium (8 x 10(-2) M). After 1 h, the pH was
      adjusted to 7.0, and the nanoparticles were purified by dialysis. Nanoparticle
      characterization included scanning electron microscopy, quasi-elastic light
      scattering, zeta potential determination, measurements of the complement
      activation induced by different polysaccharide-coated nanoparticles and of the
      antithrombic activity of heparin. RESULTS: Dispersions of spherical particles
      were obtained using various polysaccharides. The particle diameter varied from 90
      nm to several micrometers, and the zeta potential depended on the molecular
      weight and the nature and charge of the polysaccharide. Surface analysis
      performed by ESCA confirmed the presence of polysaccharides at the nanoparticle
      surface. The nanoparticles were very stable, and the biologic activity of the
      polysaccharide was preserved. Complement activation was influenced by the
      polysaccharide characteristics. CONCLUSIONS: A new method based on radical
      emulsion polymerization of isobutyl cyanoacrylate initiated by polysaccharides
      and cerium was developed to prepare nanoparticles. It leads, in a single step, to
      nanoparticles with surface properties defined by the polysaccharide. This method
      is a new concept for the development of biomimetic drug carriers with multiple
      functions.

PMID- 14661924
TI  - Structural determinants of P-glycoprotein-mediated transport of glucocorticoids.
AB  - PURPOSE: The aim of this study was to determine requisite structural features for
      P-glycoprotein-mediated transport of a series of structurally related
      glucocorticoids (GCs). METHODS: Transport experiments were conducted in wild-type
      and stably transfected MDRI LLC-PK cell line. Transport efficiency (Teff = Peff,
      B-->A / Peff, A-->B) in both cell lines was compared as a measure of passive
      diffusion and P-glycoprotein-mediated transepithelial transport for each steroid.
      Three-dimensional structure-activity relationships were built to determine how
      specific structural features within the steroids affect their P-gp-mediated
      efflux. RESULTS: Mean (+/- SD) Teff in LLC-PK cells was 1.1 +/- 0.17, indicating
      that differences in structure and partition coefficient did not affect drug flux
      in the absence of P-glycoprotein. Teff in L-MDRI cells ranged from 3.6 to 26.6,
      demonstrating the importance of glucocorticoid structure to P-glycoprotein
      transport. The rank order of Teff in MDR1 cells was: methylprednisolone>
      prednisolone > betamethasone > dexamethasone/prednisone > cortisol. There was no
      correlation between individual Teff values and partition coefficient. 3D-QSAR
      models were built using CoMFA and CoMSIA with a q2 (r2) of 0.48 (0.99) and 0.41
      (0.95), respectively. CONCLUSIONS: Nonpolar bulky substituents around the C
      6alpha position, as well as a hydrogen-bond donor at position C-11, enhance P
      glycoprotein affinity and cellular efflux, whereas bulky substituents at C-16
      diminish transporter affinity.

PMID- 14661925
TI  - Hypoxanthine transport in human glioblastoma cells and effect on cell
      susceptibility to methotrexate.
AB  - PURPOSE: Cancer cells may circumvent the cytotoxic effect of antimetabolite drugs
      that inhibit de novo nucleotide synthesis via the uptake of extracellular
      preformed nucleobases or nucleosides. The goal of this study was to investigate
      the nucleobase transport mechanism in human U-118 glioblastoma cells and to
      determine whether the purine nucleobase hypoxanthine affects cell susceptibility
      to methotrexate. METHODS: Uptake experiments were performed using 3H-labeled
      hypoxanthine. RT-PCR was used to determine the expression of nucleoside
      transporters. Methotrexate-induced apoptosis was analyzed using annexin V
      staining and FACScan analysis. RESULTS: Hypoxanthine transport in U-118 cells
      involved both carrier-mediated (Km = 10.5 +/- 6.3 microM, Vmax = 1.45 +/- 0.69
      pmol/10(5) cells/60 s) and simple diffusion processes (Kd = 0.36 +/- 0.009
      microm/10(5) cells/60 s). Uptake was sensitive to Na+ and inhibited by
      nucleobases but not nucleosides or nucleoside transport inhibitors. In contrast,
      uptake of a nucleoside, uridine, was inhibited by nucleosides but not
      nucleobases. RT-PCR analysis suggested the presence of hENT1, hENT2, and hCNTI
      nucleoside transporters in U-118 cells. In the absence of hypoxanthine,
      methotrexate inhibited U-118 cell proliferation and induced apoptosis. These
      toxic effects were diminished when hypoxanthine was present at physiologically
      relevant concentrations. CONCLUSIONS: Hypoxanthine transport in U-118 cells
      involves a Na+-dependent, high-affinity nucleobase transport system functionally
      distinct from nucleoside transporters. At physiologic concentrations,
      hypoxanthine protects glioblastoma cells from the cytotoxicity of methotrexate.

PMID- 14661926
TI  - Uptake of chitosan and associated insulin in Caco-2 cell monolayers: a comparison
      between chitosan molecules and chitosan nanoparticles.
AB  - PURPOSE: To evaluate the uptake of chitosan molecules (fCS) and nanoparticles
      (fNP), and their ability to mediate insulin transport in Caco-2 cell monolayers.
      METHODS: Cell-associated fCS and fNP were evaluated by fluorometry, trypan blue
      quenching, and confocal microscopy using FITC-labeled chitosan. Chitosan-mediated
      transport of FITC-labeled insulin was studied in Caco-2 cell monolayers cultured
      on permeable inserts. RESULTS: Caco-2 cells showed twofold higher association
      with fNP than fCS after 2-h incubation with 1 mg/ml samples. fNP uptake was a
      saturable (Km 1.04 mg/ml; Vmax 74.15 microg/mg/h), concentration- and temperature
      dependent process that was inhibited by coadministered chlorpromazine. fCS uptake
      was temperature dependent, but was less sensitive to concentration and was
      inhibited by filipin. Postuptake quenching with 100 microg/ml of trypan blue
      suggests a significant amount of intracellular fNP, although the bulk of fCS was
      extracellular. Internalized fNP were located by confocal microscopy at 15 microm
      from the apical membrane, but there was no apparent breaching of the basal
      membrane. This might explain the failure of the nanoparticles to mediate
      significant insulin transport across the Caco-2 cell monolayer. CONCLUSIONS:
      Formulation of chitosan into nanoparticles transforms its extracellular
      interactions with the Caco-2 cells to one of cellular internalization via
      clathrin-mediated endocytosis.

PMID- 14661927
TI  - In vitro permeability of poorly aqueous soluble compounds using different
      solubilizers in the PAMPA assay with liquid chromatography/mass spectrometry
      detection.
AB  - PURPOSE: This study compares the use of UV-VIS detection with liquid
      chromatography/mass spectrometry (LC/MS) detection for the PAMPA (Parallel
      Artificial Membrane Permeability Assay) permeability determination of compounds
      in the drug discovery stage. LC/MS detection offers a selective and sensitive
      method for the determination of the PAMPA permeability for compounds that do not
      contain a UV chromophore or possess a low UV extinction coefficient. To enhance
      the reliability of our permeability measurements for compounds with low aqueous
      solubility, we demonstrated the use of LC/MS detection as a means for
      facilitating the study of solubilizing agents to enhance aqueous solubility that
      normally would interfere with UV-VIS detection. In doing so, the PAMPA assay can
      be expanded to study the in vitro permeability of poorly water soluble compounds
      and evaluate the effects of solubilizers' on the membrane permeability of
      different compounds. This might be useful in selecting solubilizers for poorly
      water soluble compounds to be used for further in vivo studies. METHODS: A
      diverse set of 20 drugs using UV-VIS detection were compared with data using
      LC/MS detection. A PAMPA screening method was designed which used solubilizers
      (Brij 35, Cremophor EL, ethanol, and Tween 80) for compounds with low aqueous
      solubility. The stability of the artificial membrane was determined using various
      solubilizer concentrations (0.1-5% w/v) to ensure the phospholipid membrane was
      not disrupted. Two compounds, amiodarone and miconazole, with low aqueous
      solubility yielding an undetected response in the PAMPA assay using UV-VIS
      detection were subjected to the different solubilizing agents and their PAMPA
      permeability was measured using LC/MS detection. RESULTS: Most of the compounds
      showed similar PAMPA permeability using the two detection systems. However, for
      compounds lacking a UV chromophore or with a low UV extinction coefficient, LC/MS
      was the detection method of choice for determination of PAMPA permeability
      values. LC/MS also gave reliable quantification data for compounds containing
      impurities, as well as compounds that were not stable during the assay. Although
      many solubilizers were found to interfere with UV-VIS detection, the LC/MS
      approach was applicable to determine the permeability values of compounds with
      normally low aqueous solubility. CONCLUSIONS: LC/MS detection offered greater
      sensitivity and selectivity as compared with UV-VIS detection for the PAMPA
      assay. With this added versatility in detection, PAMPA can be used in both
      discovery and pre-formulation applications, which has not been described before.

PMID- 14661928
TI  - Determination of the dermal penetration of esterom components using microdialysis
      sampling.
AB  - PURPOSE: Esterom Solution, an investigational pharmaceutical product, is derived
      from the esterification of benzoylmethylecgonine (cocaine) in 1.2 propanediol.
      The resulting solution contains a mixture of components. Esterom Solution is
      intended to be a topical analgesic to relieve pain and increase the range of
      motion in patients suffering from acute inflammation of the shoulder or back.
      Although the components of Esterom are known, the components that are responsible
      for analgesia have only recently been identified. The purpose of this research is
      to evaluate which components have the ability to penetrate the skin, how much
      actually penetrates, and if and/or how each component is metabolized and
      distributed locally. METHODS: Linear microdialysis probes were implanted into rat
      dermis. The individual components present in the Esterom Solution were applied
      separately to the dermis directly over a probe. Dermal dialysis samples were
      collected to evaluate the dermal penetration of each compound following topical
      application. RESULTS: Following a 10 mg/50 microL application. 1.8 +/- 0.6 mM
      benzoic acid was detected at the plateau after approximately 220 min. Following
      hydroxypropyl benzoic acid application, complete hydrolysis to benzoic acid was
      observed with a plateau concentration of 137 +/- 19 microM (150 min plateau).
      When applied separately, hydroxypropyl benzoylecgonine and ecgonine penetrate the
      skin with plateau concentrations of 32 +/- 9 microM (15 h plateau) and 36 +/- 5
      microM (150 min plateau) respectively. Benzoylecgonine, the hydrolytic product of
      HP-BE, was also detected with a plateau concentration of 3.9 +/- 0.1 microM (16 h
      plateau) Applied topically, ecgonidine, methylecgonidine, benzoylecgonine, and
      hydroxypropyl ecgonidine were not detected. CONCLUSIONS: Of the components with
      analgesic activity, the only compound that penetrates the skin is hydroxypropyl
      benzoylecgonine. Dermal microdialysis was shown to be an effective technique to
      monitor the skin penetration of topically applied compounds.

PMID- 14661929
TI  - Unexpected clobetasol propionate profile in human stratum corneum after topical
      application in vitro.
AB  - PURPOSE: The validity of using drug amount-depth profiles in stratum corneum to
      predict uptake of clobetasol propionate into stratum corneum and its transport
      into deeper skin layers was investigated. METHODS: In vitro diffusion experiments
      through human epidermis were carried out using Franz-type glass diffusion cells.
      A saturated solution of clobetasol propionate in 20% (V/V) aqueous propylene
      glycol was topically applied for 48 h. Steady state flux was calculated from the
      cumulative amount of drug permeated vs. time profile. Epidermal partitioning was
      conducted by applying a saturated drug solution to both sides of the epidermis
      and allowing time to equilibrate. The tape stripping technique was used to define
      drug concentration-depth profiles in stratum corneum for both the diffusion and
      equilibrium experiments. RESULTS: The concentration-depth profile of clobetasol
      propionate in stratum corneum for the diffusion experiment is biphasic. A
      logarithmic decline of the drug concentration over the first four to five tape
      strips flattens to a relatively constant low concentration level in deeper
      layers. The drug concentration-depth profile for the equilibrium studies displays
      a similar shape. CONCLUSIONS: The shape of the concentration-depth profile of
      clobetasol propionate is mainly because of the variable partitioning coefficient
      in different stratum corneum layers.

PMID- 14661931
TI  - High bioavailabilty of alpha-tocopherol loaded into poly (DL-lactic-co-glycolic
      acid) microspheres in apolipoprotein B knockout mice.
AB  - PURPOSE: To assess the potential clinical value of alpha-tocopherol-loaded poly
      (DL-lactic-co-glycolic acid) (PLGA) microspheres, we examined the disposition
      kinetics of alpha-tocopherol after administration of the microspheres to
      apolipoprotein B (apo B) knockout mice as a model of abetalipoproteinemia.
      METHODS: PLGA microspheres containing alpha-tocopherol were prepared by a solvent
      evaporation method. The concentration of alpha-tocopherol was measured by gas
      chromatography-mass spectrometry. RESULTS: The mean value of particle size of
      alpha-tocopherol-loaded PLGA microspheres was 108 microm. The loading and the
      trapping efficiency of alpha-tocopherol in PLGA microspheres were 20.8% and
      86.6%, respectively. When alpha-tocopherol solution (25 mg/kg) was subcutaneously
      administered to apob (+/+) and apob (+/-) mice, the plasma concentrations of
      alpha-tocopherol reached a peak at 6 h and decreased to the endogenous level
      within 4 days in both types of mice. However, the area under the plasma
      concentration-time curve (AUC) of apob (+/-) mice was significantly smaller than
      that in the case of apob (+/+) mice. When alpha-tocopherol-loaded PLGA
      microspheres (100 mg/kg) were subcutaneously administered, the plasma
      concentrations of alpha-tocopherol increased slowly and remained about 2-fold
      higher than the endogenous level at 5 to 10 days after administration in both
      types of mice, and there was no significant difference between the AUC values.
      CONCLUSIONS: The PLGA microsphere preparation of alpha-tocopherol is expected to
      be a very useful drug delivery system in vitamin E supplementation therapy for
      abetalipoproteinemia.

PMID- 14661930
TI  - Poly-L-arginine enhances paracellular permeability via serine/threonine
      phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit
      nasal epithelium.
AB  - PURPOSE: The purpose of the present study is to explore whether a poly-L-arginine
      (poly-L-Arg)-induced increase in tight junctions (TJ) permeability of fluorescein
      isothiocyanate-labeled dextran (MW 4.4 kDa, FD-4) is associated with the Ca2+
      dependent signaling and occurs following the phosphorylation/dephosphorylation of
      TJ proteins. METHODS: Excised rabbit nasal epithelium was mounted in an Ussing
      type chamber for measurement of FD-4 transport and membrane conductance (Gt) in
      the presence of various inhibitors that are involved in the Ca2+-dependent
      pathway and the phosphorylation/dephosphorylation of TJ proteins. The resultant
      distribution of TJ proteins was observed using confocal laser scanning microscopy
      (CLSM) in an immunostaining. RESULTS: The increase in TJ permeability of FD4
      induced by 0.2 mg/ml poly-L-Arg was not altered by treatment with inhibitors (of
      possible Ca2+ mobilization pathways followed by exposure of poly-L-Arg,
      suggesting that the promoting effect of poly-L-Arg is independent of Ca2+-related
      signaling. On the other hand, the protein kinase C (PKC) and tyrosine phosphatase
      inhibitors suppress the increase in TJ permeability by poly-L-Arg, indicating
      that serine/threonine phosphorylation by way of Ca2+-independent PKC and tyrosine
      dephosphorylation of junction proteins may have occurred. Furthermore,
      immunofluorescent monitoring of ZO-1, a TJ associated protein, and occludin, an
      integral membrane protein localizing at TJ, after preincubation with PKC and
      tyrosine phosphatase inhibitors followed by poly-L-Arg treatment has shown that
      the internalization of ZO-1 and occludin occurred by way of serine/threonine
      phosphorylation by PKC activation and by way of tyrosine dephosphorylation,
      respectively, providing TJ disassembly. CONCLUSIONS: We conclude that poly-L-Arg
      enhances the paracellular permeability of FD-4 (i.e., macromolecules), at least,
      by way of both serine/threonine phosphorylation of ZO-1 and tyrosine
      dephosphorylation of occludin in rabbit nasal epithelium.

PMID- 14661932
TI  - In situ monitoring of wet granulation using online X-ray powder diffraction.
AB  - PURPOSE: Polymorphic transformations during the wet granulation of a metastable
      polymorph of flufenamic acid were monitored in situ using online X-ray powder
      diffraction. The resulting data were used in testing a proposed process induced
      transformation rate model, which allows the extent and occurrence of polymorphic
      transformations during wet granulation to be controlled by adjusting the
      granulation time. METHODS: A small-scale, top mixing granulator was designed for
      compatibility with novel X-ray powder diffraction equipment (available from X-Ray
      Optical Systems of East Greenbush, NY). RESULTS: The unique polycapillary optic
      and X-ray source allowed the transformation of the metastable to the stable
      polymorph to be followed during the granulation. Following a diffraction peak
      each for the metastable and stable forms demonstrated that polymorphic
      transformations during the wetting phase of granulation follow the trends
      predicted by the model. CONCLUSIONS: The advanced online monitoring may allow
      real-time control of the process by the adjustment of process parameters, such as
      granulation time, and clearly qualifies as a PAT (process analytical technology).

PMID- 14661933
TI  - Solubilization of cationic drugs in lung surfactant.
AB  - PURPOSE: The association of hydrophobic, cationic drugs with lung surfactant was
      determined to assess the pharmacokinetic implications on drug disposition and
      retention in the lung. METHODS: The distribution coefficients, K, were determined
      at 25 and 37 degrees in normal saline solution buffered at pH 7.4 for a series of
      structurally related, cationic drugs. Drugs were dispersed into lung surfactant,
      equilibrated, and then centrifuged to separate the aqueous phase from the
      surfactant pellet. Drug concentrations in the supernatant and pellet were
      determined following dilution using spectrophotometric assays. In addition, the
      apparent acid dissociation constant of quinacrine in the presence and absence of
      surfactant was determined by measuring the pH-dependent absorption spectra. The
      effect of stereochemistry on the distribution of drugs into surfactant was
      examined with (R)- and (S)-propranolol. RESULTS: The mole fraction distribution
      coefficients for amitriptyline, promethazine, promazine, ethopropazine,
      imipramine, R-propranolol, and S-propranolol at 25 degrees C were 6,560 +/- 500,
      28,400 +/- 1,500, 12,100 +/- 840, 5,480 +/- 330, 4,490 +/- 250, 8,680 +/- 260,
      8,190 +/- 530, respectively. At 37 degrees C, the distribution coefficients were
      generally smaller indicating a significant exothermic heat of transfer for these
      solutes from aqueous solution to the lung surfactant. The pKa of quinacrine was
      7.43 +/- 0.04 in aqueous solution and was shifted to 7.62 +/- 0.06 in the
      presence of lung surfactant. From this shift, the double layer potential for
      quinacrine-lung surfactant was estimated to be -0.012 V assuming a dielectric
      constant equivalent to that of water. CONCLUSIONS: Cationic drugs have very
      favorable distributions from an aqueous solution to the lipid phase of lung
      surfactant. The transfer process generally has both a large entropic and
      enthalpic contribution. The latter thermodynamic aspect may be related to the
      charge interaction between the solute and the negatively charged surfactant.
      Finally, no significant effect of stereochemistry was evident with the
      distribution of (R)- and (S)-propranolol.

PMID- 14661934
TI  - PLGA/TPGS nanoparticles for controlled release of paclitaxel: effects of the
      emulsifier and drug loading ratio.
AB  - PURPOSE: We successfully manufactured nanoparticles of biodegradable polymers for
      controlled release of paclitaxel. TPGS (d-alpha-tocopheryl polyethylene glycol
      1000 succinate) could be a novel material to make nanoparticles of high drug
      encapsulation efficiency (EE) and desired physicochemical and pharmaceutical
      properties of the drug loaded nanoparticles. Among various controlling parameters
      in the process, the present work is to elucidate the effects of the surfactant
      stabilizer and the drug loading ratio. METHODS: Paclitaxel loaded PLGA
      nanoparticles were formulated at various drug-loading ratios by a modified single
      emulsion solvent extraction/evaporation technique. TPGS was introduced either as
      the emulsifier or as a matrix material component by using different technique.
      Polyvinyl alcohol (PVA) was also used for a comparison. The nanoparticles of
      various recipes were characterized by various state-of-the-art instrument
      technology for their properties. RESULTS: The EE and the in vitro release
      behavior were found significantly influenced by the drug loading ratio and the
      surfactant stabilizer encountered. TPGS involved nanoparticles can have high EE
      and other favorable properties. CONCLUSIONS: TPGS could be a novel and effective
      emulsifier, which can result in high EE and desired properties of paclitaxel
      loaded polymeric nanoparticles.

PMID- 14661935
TI  - Improved alpha-chymotrypsin stability upon encapsulation in PLGA microspheres by
      solvent replacement.
AB  - PURPOSE: To investigate the potential of different solvents with better
      biocompatibility to replace CH2Cl2 in the encapsulation of alpha-chymotrypsin in
      poly (lactic-co-glycolic) acid (PLGA) microspheres without causing protein
      instability. METHODS: The oil-to-water (O:W) ratio in the emulsification step of
      the solid-in-oil-in-water (s/o/w) encapsulation process was optimized with
      respect to maximizing protein stability and encapsulation efficiency for various
      solvents. Formation of insoluble aggregates and residual enzyme activity were
      primarily used as stability parameters. Several solvents possessing low toxicity
      with different water solubility were used to prepare alpha-chymotrypsin loaded
      PLGA microspheres. RESULTS: The O:W ratio in the emulsification step is critical
      with respect to maintaining protein stability. This was related to the solvents'
      water solubility. In general, hydrophilic solvents were detrimental to protein
      stability and encapsulation efficiency. However, after optimization of the O:W
      ratio for solvents with different water solubility, protein stability was
      preserved during encapsulation using butyl acetate when poly (ethylene glycol)
      (PEG) was used as the emulsifying agent (ca. 1% of non-covalent aggregates and 93
      +/- 10% of residual specific activity). CONCLUSIONS: The s/o/w technique was
      successfully improved by replacing the ICH class 2 solvent CH2Cl2 with the class
      3 solvent butyl acetate without compromising alpha-chymotrypsin stability.

PMID- 14661936
TI  - Enantioselective analysis of ritalinic acids in biological samples by using a
      protein-based chiral stationary phase.
AB  - PURPOSE: This study was to develop and validate a new chiral HPLC-UV method for
      the quantitative analysis of enantiomeric ritalinic acid (RA) in human plasma.
      METHODS: An alpha1-acid glycoprotein column was used with the mobile phase
      containing 0.4% acetic acid and 0.1% dimethyloctylamine, pH 3.4. The detection of
      enantiomeric RAs was at 220 nm. RESULTS: A baseline separation for d- and l-RA
      was achieved by a separation factor of 2.08. Methylphenidate, the precursor of
      RA, was eluted with the front solvent, and thus does not interfere in the
      analysis of RA in our method. The assay was successfully applied for the in vitro
      analysis of enantiomeric ritalinic acids produced by human and dog plasma and dog
      liver. CONCLUSIONS: Data demonstrated that the esterase(s) in human plasma
      metabolize d-methylphenidate faster than its l-isomer. The yielded intrinsic
      clearances (Clint) are 1.02 and 2.17 microl/min/mg protein, respectively, for d
      and l-methylphenidate.

PMID- 14661937
TI  - Recommendations for the bioanalytical method validation of ligand-binding assays
      to support pharmacokinetic assessments of macromolecules.
AB  - PURPOSE: With this publication a subcommittee of the AAPS Ligand Binding Assay
      Bioanalytical Focus Group (LBABFG) makes recommendations for the development,
      validation, and implementation of ligand binding assays (LBAs) that are intended
      to support pharmacokinetic and toxicokinetic assessments of macromolecules.
      METHODS: This subcommittee was comprised of 10 members representing
      Pharmaceutical, Biotechnology, and the contract research organization industries
      from the United States, Canada, and Europe. Each section of this consensus
      document addresses a specific analytical performance characteristic or aspect for
      validation of a LBA. Within each section the topics are organized by an assay's
      life cycle, the development phase, pre-study validation, and in-study validation.
      Because unique issues often accompany bioanalytical assays for macromolecules,
      this document should be viewed as a guide for designing and conducting the
      validation of ligand binding assays. RESULTS: Values of +/- 20% (25% at the lower
      limit of quantification [LLOQ]) are recommended as default acceptance criteria
      for accuracy (% relative error [RE], mean bias) and interbatch precision
      (%coefficient of variation [CV]). In addition, we propose as secondary criteria
      for method acceptance that the sum of the interbatch precision (%CV) and the
      absolute value of the mean bias (%RE) be less than or equal to 30%. This added
      criterion is recommended to help ensure that in-study runs of test samples will
      meet the proposed run acceptance criteria of 4-6-30. Exceptions to the proposed
      process and acceptance criteria are appropriate when accompanied by a sound
      scientific rationale. CONCLUSIONS: In this consensus document, we attempt to make
      recommendations that are based on bioanalytical best practices and statistical
      thinking for development and validation of LBAs.

PMID- 14661938
TI  - District health systems in a neoliberal world: a review of five key policy areas.
AB  - District health systems, comprising primary health care and first referral
      hospitals, are key to the delivery of basic health services in developing
      countries. They should be prioritized in resource allocation and in the building
      of management and service capacity. The relegation in the World Health Report
      2000 of primary health care to a 'second generation' reform--to be superseded by
      third generation reforms with a market orientation--flows from an analysis that
      is historically flawed and ideologically biased. Primary health care has
      struggled against economic crisis and adjustment and a neoliberal ideology often
      averse to its principles. To ascribe failures of primary health care to a
      weakness in policy design, when the political economy has starved it of
      resources, is to blame the victim. Improvement in the working and living
      conditions of health workers is a precondition for the effective delivery of
      public health services. A multidimensional programme of health worker
      rehabilitation should be developed as the foundation for health service recovery.
      District health systems can and should be financed (at least mainly) from public
      funds. Although in certain situations user fees have improved the quality and
      increased the utilization of primary care services, direct charges deter health
      care use by the poor and can result in further impoverishment. Direct user fees
      should be replaced progressively by increased public finance and, where possible,
      by prepayment schemes based on principles of social health insurance with public
      subsidization. Priority setting should be driven mainly by the objective to
      achieve equity in health and wellbeing outcomes. Cost effectiveness should enter
      into the selection of treatments for people (productive efficiency), but not into
      the selection of people for treatment (allocative efficiency). Decentralization
      is likely to be advantageous in most health systems, although the exact form(s)
      should be selected with care and implementation should be phased in after
      adequate preparation. The public health service should usually play the lead
      provider role in district health systems, but non-government providers can be
      contracted if needed. There is little or no evidence to support proactive
      privatization, marketization or provider competition. Democratization of
      political and popular involvement in health enhances the benefits of
      decentralization and community participation. Integrated district health systems
      are the means by which specific health programmes can best be delivered in the
      context of overall health care needs. International assistance should address
      communicable disease control priorities in ways that strengthen local health
      systems and do not undermine them. The Global Fund to Fight AIDS, Tuberculosis
      and Malaria should not repeat the mistakes of the mass campaigns of past decades.
      In particular, it should not set programme targets that are driven by an
      international agenda and which are achievable only at the cost of an adverse
      impact on sustainable health systems. Above all the targets must not retard the
      development of the district health systems so badly needed by the rural poor.

PMID- 14661939
TI  - A code of best practice for disease control programmes to avoid damaging health
      care services in developing countries.
AB  - How should we implement disease control programmes so as to strengthen existing
      health systems? To answer this question, we re-examined the integration of these
      programmes from a managerial perspective. Based on a literature review, we
      concluded that integration is essential in the majority of cases. We went on to
      examine the mechanisms whereby the integration of disease control activities can
      jeopardize health care delivery, resulting in low service utilization, low
      detection and cure rates, and patient delays. To do this we clustered disease
      control programmes into three categories and assessed the impact of each on local
      health care facilities. From these results, we suggest a series of measures
      designed to help aid agencies and national governments support local health care
      infrastructures or, as a minimum, avoid damaging them. Whilst some vertical
      programmes should never be integrated, two conditions are essential to the
      integration of others: (1) Disease control needs to be integrated with general
      health care delivery--which implies the possibility to deliver general
      practice/family medicine care in publicly oriented health services. (2)
      Integration of both operational and administrative aspects should take place
      simultaneously. Any health policies in developing countries tending to allocate
      disease control programmes to government facilities and general health care to
      private facilities preclude their integration. They risk unravelling the fabric
      on which both disease control and health care delivery depend.

PMID- 14661940
TI  - Stronger health systems for more effective HIV/AIDS prevention and care.
AB  - Of the 42 million living with HIV/AIDS world-wide some 90% live in developing
      countries. The international community acknowledges the devastating impact of
      HIV/AIDS on development and over the past few years resources to control HIV/AIDS
      have increased considerably. We argue that strengthening of health systems is a
      necessary prerequisite for improving the prevention of HIV infection and the care
      of HIV-infected persons. Sexual behaviour change requires a multidisciplinary
      approach, but health services play a crucial role in detection and treatment of
      other sexually transmitted infections; HIV counselling and testing; prevention of
      mother-to-child transmission of HIV; and care of HIV-infected patients.
      Increasing access to antiretroviral treatment especially poses formidable
      challenges to health authorities in developing countries. Additional resources
      for the prevention of HIV-infection and the care of HIV-infected persons may not
      have the desired impact if health systems in developing countries are not
      strengthened. Further, any activity in the area of HIV/AIDS prevention and care,
      carried out within health services, can have a positive ripple effect on other
      health care activities and vice versa. This interactive effect needs to be
      acknowledged and built on.

PMID- 14661941
TI  - Strong general health care systems: a prerequisite to reach global tuberculosis
      control targets.
AB  - We argue that tuberculosis control cannot reach its proposed global targets
      without investment in an adequate network of accessible, effective and
      comprehensive health services. Lessons from the past are reviewed. They
      underscore that passive case-detection and adequate case management is the
      central technical strategy for tuberculosis control. There is no compelling
      evidence to support active case-detection in the general population. We elaborate
      on why a strong health care system is a prerequisite in the framework of case
      detection and treatment. The necessity to improve quality and accessibility of
      general health services for ensuring early detection and subsequent cure is
      demonstrated. It is argued why the need for strong public health care system
      becomes even more eminent in the light of the tuberculosis/HIV dual epidemics and
      of the rapid growth of unregulated private-for-profit services. We finally
      examine the financial gaps for tuberculosis control and discuss the need for
      allocating more resources to the strengthening of general health care systems.

PMID- 14661942
TI  - Health systems in developing countries: public sector managers and the management
      of contradictions and change.
AB  - Health sector reform in the past decade has tended to focus on remodelling
      institutional relations and changing methods of health system financing. Little
      attention has been paid to human resources. This paper focuses on one category of
      health sector staff, health managers and planners, and the tensions they face in
      carrying out their roles. An understanding of these tensions has been neglected
      in the policy-making process. The paper is divided into two parts. Firstly, it
      will set out the nature of three tensions that public sector health managers and
      planners face: changes in the health care system; the contradictions between
      public interest and private gain; and changes in the forms of accountability.
      Secondly, it will suggest ways forward in relation to these problems, paying
      particular attention to the role of international agencies.

PMID- 14661943
TI  - Quality standards for health care delivery and management in publicly oriented
      health services.
AB  - In 1999, the multidisciplinary Tavistock group prepared a generic statement of
      ethical principles to govern health care systems. This paper elaborates on these
      principles in two directions. First, it develops a set of quality standards,
      based on ethical principles, intended to regulate health care delivery and
      service management. Second, it focuses them on 'publicly oriented' (not
      necessarily governmental) as opposed to 'for profit' (not necessarily private)
      services. We propose ten principles or quality standards for these services, part
      of which relate to the individual patients, others to the community. They are
      political as well as technical, and can be used to inspire health policies,
      contracts issued by governments, and identification of partners by aid agencies.
      We analyse their application in key areas of health care by publicly oriented and
      for-profit health care organizations standards in developing countries, and
      conclude that the latter are unlikely to adopt the proposed standards. We further
      elaborate on the implications of the standards for publicly oriented services,
      focusing on care delivery and patient-centred care, family and community
      medicine, services management and disease control. Using these criteria for a
      renewed compact between authorities, health professionals and communities may
      help to motivate health professionals by bridging the gap between their
      professional and social-political identity.

PMID- 14661944
TI  - Health workforce imbalances in times of globalization: brain drain or
      professional mobility?
AB  - The health workforce is of strategic importance to the performance of national
      health systems as well as of international disease control initiatives. The brain
      drain from rural to urban areas, and from developing to industrialized countries
      is a long-standing phenomenon in the health professions but has in recent years
      taken extreme proportions, particularly in Africa. Adopting the wider perspective
      of health workforce balances, this paper presents an analysis of the underlying
      mechanisms of health professional migration and possible strategies to reduce its
      negative impact on health services. The opening up of international borders for
      goods and labour, a key strategy in the current liberal global economy, is
      accompanied by a linguistic shift from 'human capital flight' and 'brain drain'
      to 'professional mobility' or 'brain circulation'. In reality, this mobility is
      very asymmetrical, to the detriment of less developed countries, which lose not
      only much-needed human resources, but also considerable investments in education
      and fiscal income. It is argued that low professional satisfaction and the
      decreasing social valuation of the health professionals are important
      determinants of the decreasing attraction of the health professions, which
      underlies both the push from the exporting countries, as well as the pull from
      the recipient countries. Solutions should therefore be based on this wider
      perspective, interrelating health workforce imbalances between, but also within
      developing and developed countries.

PMID- 14661945
TI  - "In the beginning": initiation of minus strand DNA synthesis in retroviruses and
      LTR-containing retrotransposons.
AB  - Sequestering a host-coded tRNA for initiation of minus (-) strand DNA synthesis
      is central to the reverse transcription cycle of a number of retroviruses and
      long terminal repeat (LTR) retrotransposons. However, "self-priming" from a
      hydrolysis product of the viral genome has been observed for the LTR
      retrotransposon Tf1 and most likely exists for related elements. Furthermore, in
      contrast to retroviruses, where DNA synthesis is initiated from the 3'-terminus
      of the cognate tRNA primer, examples are available where nucleotides of the tRNA
      anticodon domain are complementary to the viral primer binding site (PBS),
      necessitating internal cleavage of the primer to provide the appropriate 3'-OH
      for DNA synthesis. Thus, although the ensuing steps of reverse transcription are
      common to these elements, several variations in which the replication primer is
      used have been exploited. In addition, the PBS of the viral RNA genome can vary
      in size from an 11 nt sequence, through a bipartite cis-acting element, to 18
      contiguous nucleotides complementary to the 3'-end of the replication primer.
      These diverse tRNA-viral RNA interactions, and their consequences for initiation
      of (-) strand DNA synthesis, are the subject of this review.

PMID- 14661946
TI  - Association of DNA quadruplexes through G:C:G:C tetrads. Solution structure of
      d(GCGGTGGAT).
AB  - The structure formed by the DNA sequence d(GCGGTGGAT) in a 100 mM Na(+) solution
      has been determined using molecular dynamics calculations constrained by distance
      and dihedral restraints derived from NMR experiments performed at isotopic
      natural abundance. The sequence folds into a dimer of dimers. Each symmetry
      related half contains two parallel stranded G:G:G:G tetrads flanked by an A:A
      mismatch and by four-stranded G:C:G:C tetrads. Each of the two juxtaposed G:C:G:C
      tetrads is composed of alternating antiparallel strands from the two halves of
      the dimer. For each single strand, a thymine intersperses a double chain reversal
      connecting the juxtaposed G:G:G:G tetrads. This architecture has potential
      implications in genetic recombination. It suggests a pathway for oligomerization
      involving association of quadruplex entities through GpC steps.

PMID- 14661947
TI  - Molecular basis for Gcn5/PCAF histone acetyltransferase selectivity for histone
      and nonhistone substrates.
AB  - Histone acetyltransferase (HAT) proteins often exhibit a high degree of
      specificity for lysine-bearing protein substrates. We have previously reported on
      the structure of the Tetrahymena Gcn5 HAT protein (tGcn5) bound to its preferred
      histone H3 substrate, revealing the mode of substrate binding by the Gcn5/PCAF
      family of HAT proteins. Interestingly, the Gcn5/PCAF HAT family has a remarkable
      ability to acetylate lysine residues within diverse cognate sites such as those
      found around lysines 14, 8, and 320 of histones H3, H4, and p53, respectively. To
      investigate the molecular basis for this, we now report on the crystal structures
      of tGcn5 bound to 19-residue histone H4 and p53 peptides. A comparison of these
      structures with tGcn5 bound to histone H3 reveals that the Gcn5/PCAF HATs can
      accommodate divergent substrates by utilizing analogous interactions with the
      lysine target and two C-terminal residues with a related chemical nature,
      suggesting that these interactions play a general role in Gcn5/PCAF substrate
      binding selectivity. In contrast, while the histone H3 complex shows extensive
      interactions with tGcn5 and peptide residues N-terminal to the target lysine, the
      corresponding residues in histone H4 and p53 are disordered, suggesting that the
      N-terminal substrate region plays an important role in the enhanced affinity of
      the Gcn5/PCAF HAT proteins for histone H3. Together, these studies provide a
      framework for understanding the substrate selectivity of HAT proteins.

PMID- 14661948
TI  - Simultaneous DNA binding and bending by EcoRV endonuclease observed by real-time
      fluorescence.
AB  - The complete catalytic cycle of EcoRV endonuclease has been observed by combining
      fluorescence anisotropy with fluorescence resonance energy transfer (FRET)
      measurements. Binding, bending, and cleavage of substrate oligonucleotides were
      monitored in real time by rhodamine-x anisotropy and by FRET between rhodamine
      and fluorescein dyes attached to opposite ends of a 14-mer DNA duplex. For the
      cognate GATATC site binding and bending are found to be nearly simultaneous, with
      association and bending rate constants of (1.45-1.6) x 10(8) M(-1) s(-1). On the
      basis of the measurement of k(off) by a substrate-trapping approach, the
      equilibrium dissociation constant of the enzyme-DNA complex in the presence of
      inhibitory calcium ions was calculated as 3.7 x 10(-12) M from the kinetic
      constants. Further, the entire DNA cleavage reaction can be observed in the
      presence of catalytic Mg(2+) ions. These measurements reveal that the binding and
      bending steps occur at equivalent rates in the presence of either Mg(2+) or
      Ca(2+), while a slow decrease in fluorescence intensity following bending
      corresponds to k(cat), which is limited by the cleavage and product dissociation
      steps. Measurement of k(on) and k(off) in the absence of divalent metals shows
      that the DNA binding affinity is decreased by 5000-fold to 1.4 x 10(-8) M, and no
      bending could be detected in this case. Together with crystallographic studies,
      these data suggest a model for the induced-fit conformational change in which the
      role of divalent metal ions is to stabilize the sharply bent DNA in an
      orientation suitable for accessing the catalytic transition state.

PMID- 14661949
TI  - Conformational change in the 16S rRNA in the Escherichia coli 70S ribosome
      induced by P/P- and P/E-site tRNAPhe binding.
AB  - The effects of P/P- and P/E-site tRNA(Phe) binding on the 16S rRNA structure in
      the Escherichia coli 70S ribosome were investigated using UV cross-linking. The
      identity and frequency of 16S rRNA intramolecular cross-links were determined in
      the presence of deacyl-tRNA(Phe) or N-acetyl-Phe-tRNA(Phe) using poly(U) or an
      mRNA analogue containing a single Phe codon. For N-acetyl-Phe-tRNA(Phe) with
      either poly(U) or the mRNA analogue, the frequency of an intramolecular cross
      link C967 x C1400 in the 16S rRNA was decreased in proportion to the binding
      stoichiometry of the tRNA. A proportional effect was true also for deacyl
      tRNA(Phe) with poly(U), but the decrease in the C967 x C1400 frequency was less
      than the tRNA binding stoichiometry with the mRNA analogue. The inhibition of the
      C967 x C1400 cross-link was similar in buffers with, or without, polyamines. The
      exclusive participation of C967 with C1400 in the cross-link was confirmed by RNA
      sequencing. One intermolecular cross-link, 16S rRNA (C1400) to tRNA(Phe)(U33),
      was made with either poly(U) or the mRNA analogue. These results indicate a
      limited structural change in the small subunit around C967 and C1400 during tRNA
      P-site binding sensitive to the type of mRNA that is used. The absence of the
      C967 x C1400 cross-link in 70S ribosome complexes with tRNA is consistent with
      the 30S and 70S crystal structures, which contain tRNA or tRNA analogues; the
      occurrence of the cross-link indicates an alternative arrangement in this region
      in empty ribosomes.

PMID- 14661950
TI  - Crystal structure of a ternary complex of the alcohol dehydrogenase from
      Sulfolobus solfataricus.
AB  - The crystal structure of a ternary complex of the alcohol dehydrogenase from the
      archaeon Sulfolobus solfataricus (SsADH) has been determined at 2.3 A. The
      asymmetric unit contains a dimer with a NADH and a 2-ethoxyethanol molecule bound
      to each subunit. The comparison with the apo structure of the enzyme reveals that
      this medium chain ADH undergoes a substantial conformational change in the apo
      holo transition, accompanied by loop movements at the domain interface. The
      extent of domain closure is similar to that observed for the classical horse
      liver ADH, although some differences are found which can be related to the
      different oligomeric states of the enzymes. Compared to its apo form, the SsADH
      ternary complex shows a change in the ligation state of the active site zinc ion
      which is no longer bound to Glu69, providing additional evidence of the dynamic
      role played by the conserved glutamate residue in ADHs. In addition, the
      structure presented here allows the identification of the substrate site and
      hence of the residues that are important in the binding of both the substrate and
      the coenzyme.

PMID- 14661951
TI  - Solution structure of a novel disintegrin, salmosin, from Agkistrondon halys
      venom.
AB  - Disintegrins are potent inhibitors of both platelet aggregation and integrin
      dependent cell adhesion. A new disintegrin, salmosin, isolated from the venom of
      the Korean snake Agkistrodon halys brevicaudus, has been characterized by mass
      spectrometry and NMR spectroscopy, and its in vitro biological activity has been
      assessed. The IC(50) value of the purified salmosin was determined to be 2.2 nM
      in an assay for the inhibition of glycoprotein IIb-IIIa/fibrinogen interaction.
      Salmosin also inhibited the bovine capillary endothelial cell proliferation
      induced by bFGF in a dose-dependent manner. The NMR solution structures were well
      converged with a root-mean-square deviation of 0.76 A for backbone atoms among
      the 20 lowest energy structures, except for the arginylglycylaspartic acid (RGD)
      loop. The structure revealed that the conserved RGD motif with an unusual finger
      shape is distal from the rigid core of the C-terminal domain. Furthermore, even
      though the RGD motif did not interact with the hydrophobic core of the protein,
      it was stabilized by a network of molecular contacts through a small antiparallel
      beta-sheet comprising residues of Ile46-Ala50 and Asp54-Tyr58. Last, the
      electrostatic charge distribution on the surface of salmosin differs dramatically
      from that of other disintegrin proteins in that there is a cluster of negatively
      charged residues in close proximity to the RGD loop.

PMID- 14661952
TI  - Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target
      specificity and activation of the kinase.
AB  - NDR, a nuclear serine/threonine kinase, belongs to the subfamily of Dbf2 kinases
      that is critical to the morphology and proliferation of cells. The activity of
      NDR kinase is modulated in a Ca(2+)/S100B-dependent manner by phosphorylation of
      Ser281 in the catalytic domain and Thr444 in the C-terminal regulatory domain.
      S100B, which is a member of the S100 subfamily of EF-hand proteins, binds to a
      basic/hydrophobic sequence at the junction of the N-terminal regulatory and
      catalytic domains (NDR(62-87)). Unlike calmodulin-dependent kinases, regulation
      of NDR by S100B is not associated with direct autoinhibition of the active site,
      but rather involves a conformational change in the catalytic domain triggered by
      Ca(2+)/S100B binding to the junction region. To gain further insight into the
      mechanism of activation of the kinase, studies have been carried out on
      Ca(2+)/S100B in complex with the intact N-terminal regulatory domain, NDR(1-87).
      Multidimensional heteronuclear NMR analysis showed that the binding mode and
      stoichiometry of a peptide fragment of NDR (NDR(62-87)) is the same as for the
      intact N-terminal regulatory domain. The solution structure of Ca(2+)/S100B and
      NDR(62-87) has been determined. One target molecule is found to associate with
      each subunit of the S100B dimer. The peptide adopts three turns of helix in the
      bound state, and the complex is stabilized by both hydrophobic and electrostatic
      interactions. These structural studies, in combination with available biochemical
      data, have been used to develop a model for calcium-induced activation of NDR
      kinase by S100B.

PMID- 14661953
TI  - Evolution of enzymatic activity in the enolase superfamily: structural and
      mutagenic studies of the mechanism of the reaction catalyzed by o
      succinylbenzoate synthase from Escherichia coli.
AB  - o-Succinylbenzoate synthase (OSBS) from Escherichia coli, a member of the enolase
      superfamily, catalyzes an exergonic dehydration reaction in the menaquinone
      biosynthetic pathway in which 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1
      carboxylate (SHCHC) is converted to 4-(2'-carboxyphenyl)-4-oxobutyrate (o
      succinylbenzoate or OSB). Our previous structural studies of the Mg(2+).OSB
      complex established that OSBS is a member of the muconate lactonizing enzyme
      subgroup of the superfamily: the essential Mg(2+) is coordinated to carboxylate
      ligands at the ends of the third, fourth, and fifth beta-strands of the
      (beta/alpha)(7)beta-barrel catalytic domain, and the OSB product is located
      between the Lys 133 at the end of the second beta-strand and the Lys 235 at the
      end of the sixth beta-strand [Thompson, T. B., Garrett, J. B., Taylor, E. A,
      Meganathan, R., Gerlt, J. A., and Rayment, I. (2000) Biochemistry 39, 10662-76].
      Both Lys 133 and Lys 235 were separately replaced with Ala, Ser, and Arg
      residues; all six mutants displayed no detectable catalytic activity. The
      structure of the Mg(2+).SHCHC complex of the K133R mutant has been solved at 1.62
      A resolution by molecular replacement starting from the structure of the
      Mg(2+).OSB complex. This establishes the absolute configuration of SHCHC: the C1
      carboxylate and the C6-OH leaving group are in a trans orientation, requiring
      that the dehydration proceed via a syn stereochemical course. The side chain of
      Arg 133 is pointed out of the active site so that it cannot function as a general
      base, whereas in the wild-type enzyme complexed with Mg(2+).OSB, the side chain
      of Lys 133 is appropriately positioned to function as the only acid/base catalyst
      in the syn dehydration. The epsilon-ammonium group of Lys 235 forms a cation-pi
      interaction with the cyclohexadienyl moiety of SHCHC, suggesting that Lys 235
      also stabilizes the enediolate anion intermediate in the syn dehydration via a
      similar interaction.

PMID- 14661954
TI  - Solution structure of Alo-3: a new knottin-type antifungal peptide from the
      insect Acrocinus longimanus.
AB  - Insect peptides are key elements of the innate immunity against bacteria and
      fungi. These molecules offer remarkable properties: high efficacy, a low
      probability of resistance, limited toxicity, and immunogenicity. In this context,
      we are investigating several classes of peptides, and we have been successful in
      identifying biologically important classes of peptides and small molecules that
      will provide a stream of drug candidates for treating severe, life-threatening,
      hospital-acquired infections and other pathologies of high medical need.
      Recently, we have isolated a new class of antifungal peptides from the
      coleopteran Acrocinus longimanus. Three homologous peptides, Alo-1, Alo-2, and
      Alo-3, with sequence identity above 80% and active against the Candida glabrata
      yeast strain were identified. Alo-3 displayed the highest activity against
      Candida glabrata and was thus chosen for structure determination using NMR
      spectroscopy and molecular modeling. Alo-3 contains six cysteine residues forming
      three disulfide bridges. The pairing of the cysteines was assessed using
      ambiguous disulfide restraints within the ARIA software, allowing us to establish
      that Alo-3 belongs to the inhibitor cystine-knot family. It exhibits all the
      structural features characteristic of the knottin fold, namely, a triple-stranded
      antiparallel beta-sheet with a long flexible loop connecting the first strand to
      the second strand and a series of turns. To our knowledge, Alo-3 is the first
      peptide from insects with antimicrobial activity adopting the knottin fold. Alo-3
      shows a level of activity significantly higher against C. glabrata than Alo-1 or
      Alo-2. It has no negatively charged residues and displays on its surface a
      cationic pole that may account for its antifungal activity. This finding is
      validated by the comparison of the structure of Alo-3 with the structure of other
      structurally related peptides from other sources also showing antifungal
      activity.

PMID- 14661955
TI  - Molecular dynamics of the long neurotoxin LSIII.
AB  - Long neurotoxins bind tightly and specifically to the nicotinic acetylcholine
      receptor (AChR) in postsynaptic membranes and are useful for exploring the
      biology of synapses. In crystallographic studies of long neurotoxins the
      principal binding loop appears disordered, but the NMR solution structure of the
      long neurotoxin LSIII revealed significant local order, even though the loop is
      disordered with respect to the globular core. A possible mechanism for conferring
      global disorder while preserving local order is rigid-body motion of the loop
      about a hinge region. Here we report investigations of LSIII dynamics based on
      (13)C(alpha) magnetic relaxation rates and molecular dynamics simulation. The
      relaxation rates and MD simulation both confirm the hypothesis of rigid-body
      motion of the loop and place bounds on the extent and time scale of the motion.
      The bending motion of the loop is slow compared to the rapid fluctuations of
      individual dihedral angles, reflecting the collective nature and largely entropic
      free energy profile for hinge bending. The dynamics of the central binding loop
      in LSIII illustrates two distinct mechanisms by which molecular dynamics directly
      impacts biological activity. The relative rigidity of key residues involved in
      recognition at the tip of the central binding loop lowers the otherwise
      substantial entropic cost of binding. Large excursions of the loop hinge angle
      may endow the protein with structural plasticity, allowing it to adapt to
      conformational changes induced in the receptor.

PMID- 14661956
TI  - Identification of the active conformation and the importance of length of the
      flexible loop 72-83 in regulating the conformational change of undecaprenyl
      pyrophosphate synthase.
AB  - Increasing evidence has shown that intrinsic disorder of proteins plays a key
      role in their biological functions. In the case of undecaprenyl pyrophosphate
      synthase (UPPs), which catalyzes the chain elongation of farnesyl pyrophosphate
      (FPP) to undecaprenyl pyrophosphate via eight consecutive condensation reactions
      with isopentenyl pyrophosphate, a highly flexible loop 72-83 was previously
      linked to protein conformational change required for catalysis [Chen, Y. H.,
      Chen, A. P.-C., Chen, C. T., Wang, A. H.-J., and Liang, P. H., (2002) J. Biol.
      Chem. 277, 7369-7376]. The crystal structure and fluorescence studies suggested
      that the alpha3 helix connected to the loop moves toward the active site when the
      substrate is bound. To identify the active conformation and study the role of the
      loop for conformational change, the UPPs mutants with amino acids inserted into
      or deleted from the loop were examined. The inserted mutant with extra Ala
      residues fails to display the intrinsic fluorescence quenching upon FPP binding,
      and its crystal structure reveals only the open form. These phenomena appear to
      be different from the wild-type enzyme in which open and closed conformers were
      observed and suggest that the extended loop fails to pull the alpha3 helix and/or
      the extra amino acids in the loop cause steric hindrance on the alpha3 helix
      movement. The loop-shortening mutants with deletion of V82 and S83 or S72 also
      adopt an open conformation with the loop stretched, although they show decreased
      intrinsic fluorescence with FPP bound, similar to that seen in the wild-type
      enzyme. We conclude that the closed conformation is apparently the active
      conformation. Change of the length of the loop 72-83 impairs the ability of
      conformational change and causes remarkably lower activity of UPPs.

PMID- 14661957
TI  - Phosphorylation and mutation of human cardiac troponin I deferentially
      destabilize the interaction of the functional regions of troponin I with troponin
      C.
AB  - We have utilized 2D [(1)H,(15)N]HSQC NMR spectroscopy to elucidate the binding of
      three segments of cTnI in native, phosphorylated, and mutated states to cTnC. The
      near N-terminal region (cRp; residues 34-71) contains the protein kinase C (PKC)
      phosphorylation sites S41 and S43, the inhibitory region (cIp; residues 128-147)
      contains another PKC site T142 and a familial hypertrophic cardiomyopathy (FHC)
      mutation R144G, and the switch region (cSp; residues 147-163) contains the novel
      p21-activated kinase (PAK) site S149 and another FHC mutation R161W. While
      S41/S43 phosphorylation of cRp had minimal disruption in the interaction of cRp
      and cTnC.3Ca(2+), T142 phosphorylation reduced the affinity of cIp for
      cCTnC.2Ca(2+) by approximately 14-fold and S149 phosphorylation reduced the
      affinity of cSp for cNTnC.Ca(2+) by approximately 10-fold. The mutation R144G
      caused an approximately 6-fold affinity decrease of cIp for cCTnC.2Ca(2+) and
      mutation R161W destabilized the interaction of cSp and cNTnC.Ca(2+) by
      approximately 1.4-fold. When cIp was both T142 phosphorylated and R144G mutated,
      its affinity for cCTnC.2Ca(2+) was reduced approximately 19-fold, and when cSp
      was both S149 phosphorylated and R161W mutated, its affinity for cNTnC.Ca(2+) was
      reduced approximately 4-fold. Thus, while the FHC mutation R144G enhances the
      effect of T142 phosphorylation on the interaction of cIp and cCTnC.2Ca(2+), the
      FHC mutation R161W suppresses the effect of S149 phosphorylation on the
      interaction of cSp and cNTnC.Ca(2+), demonstrating linkages between the FHC
      mutation and phosphorylation of cTnI. The observed alterations corroborate well
      with structural data. These results suggest that while the modifications in the
      cRp region have minimal influence, those in the key functional cIp-cSp region
      have a pronounced effect on the interaction of cTnI and cTnC, which may correlate
      with the altered myofilament function and cardiac muscle contraction under
      pathophysiological conditions.

PMID- 14661958
TI  - Increased rigidity of domain structures enhances the stability of a mutant enzyme
      created by directed evolution.
AB  - A mutant of kanamycin nucleotidyltransferase (KNT) was previously created by
      directed evolution. This mutant, HTK, has 19 amino acid substitutions, which
      increase the thermostability by 20 degrees C. In this study, we have examined to
      what extent each mutation contributes to the increased stability and analyzed how
      the mutations affect the structure of KNT at 72 degrees C using molecular
      dynamics simulations. The effects of some mutations on the stability are simply
      additive, but those of others are cooperative. Mutations with large effects on
      the stability are introduced into the N-terminal domain, which appears to be less
      stable than the C-terminal domain. Results of the molecular dynamics simulations
      have indicated that the rigidity of the domain structures is increased by the
      mutations: at 72 degrees C, the intradomain fluctuations of HTK are decreased,
      and in turn, its interdomain motions are pronounced, whereas the structure of the
      preevolved KNT fluctuates randomly. Chemical modification experiments of cysteine
      residues have shown that the cysteine residues of HTK are less accessible to an
      SH reagent than those of the preevolved KNT. The present results suggest that the
      19 mutations of HTK stabilize KNT by affecting the dynamic behavior of the
      structure of this enzyme without significantly changing its static overall
      structure.

PMID- 14661959
TI  - RP4 repressor protein KorB binds to the major groove of the operator DNA: a Raman
      study.
AB  - KorB is a member of the ParB family of bacterial partitioning proteins. The
      protein encoded by the conjugative plasmid RP4 is part of the global control
      circuit and regulates the expression of plasmid genes, the products of which are
      involved in replication, transfer, and stable inheritance. KorB is a homodimeric
      protein which binds to palindromic 13 bp DNA sequences [5'-TTTAGC((G)/(C))GCTAAA
      3'] present 12 times in the 60 kb plasmid. Each KorB subunit is composed of two
      domains; the C-domain is responsible for the dimerization of the protein, whereas
      the N-terminal domain recognizes and binds to the operator sequence (O(B)). Here
      we describe results of a Raman spectroscopic study of the interaction of the N
      domain with a double-stranded model oligonucleotide composed of the palindromic
      binding sequence and terminal 5'-A(Br)U and AG-3' bases. Comparison of the Raman
      spectra of the free KorB N-domain and O(B) DNA with the spectrum of the complex
      reveals large differences. KorB-N binds in the major groove of the O(B) DNA, and
      the interactions induce changes in the DNA backbone and in the secondary
      structure of the protein.

PMID- 14661960
TI  - Thermodynamic cycle analysis and inhibitor design against beta-lactamase.
AB  - Beta-lactamases are the most widespread resistance mechanism to beta-lactam
      antibiotics, such as the penicillins and cephalosporins. Transition-state
      analogues that bind to the enzymes with nanomolar affinities have been introduced
      in an effort to reverse the resistance conferred by these enzymes. To understand
      the origins of this affinity, and to guide design of future inhibitors, double
      mutant thermodynamic cycle experiments were undertaken. An unexpected hydrogen
      bond between the nonconserved Asn289 and a key inhibitor carboxylate was observed
      in the X-ray crystal structure of a 1 nM inhibitor (compound 1) in complex with
      AmpC beta-lactamase. To investigate the energy of this hydrogen bond, the mutant
      enzyme N289A was made, as was an analogue of 1 that lacked the carboxylate
      (compound 2). The differential affinity of the four different protein and
      analogue complexes indicates that the carboxylate-amide hydrogen bond contributes
      1.7 kcal/mol to overall binding affinity. Synthesis of an analogue of 1 where the
      carboxylate was replaced with an aldehyde led to an inhibitor that lost all this
      hydrogen bond energy, consistent with the importance of the ionic nature of this
      hydrogen bond. To investigate the structural bases of these energies, X-ray
      crystal structures of N289A/1 and N289A/2 were determined to 1.49 and 1.39 A,
      respectively. These structures suggest that no significant rearrangement occurs
      in the mutant versus the wild-type complexes with both compounds. The mutant
      enzymes L119A and L293A were made to investigate the interaction between a phenyl
      ring in 1 and these residues. Whereas deletion of the phenyl itself diminishes
      affinity by 5-fold, the double-mutant cycles suggest that this energy does not
      come through interaction with the leucines, despite the close contact in the
      structure. The energies of these interactions provide key information for the
      design of improved inhibitors against beta-lactamases. The high magnitude of the
      ion-dipole interaction between Asn289 and the carboxylate of 1 is consistent with
      the idea that ionic interactions can provide significant net affinity in
      inhibitor complexes.

PMID- 14661961
TI  - Interactions between cytochrome c2 and photosynthetic reaction center from
      Rhodobacter sphaeroides: changes in binding affinity and electron transfer rate
      due to mutation of interfacial hydrophobic residues are strongly correlated.
AB  - The structure of the complex between cytochrome c(2) (cyt) and the photosynthetic
      reaction center (RC) from Rhodobacter sphaeroides shows contacts between
      hydrophobic residues Tyr L162, Leu M191, and Val M192 on the RC and the surface
      of the cyt [Axelrod et al. (2002) J. Mol. Biol. 319, 501-515]. The role of these
      hydrophobic residues in binding and electron transfer was investigated by
      replacing them with Ala and other residues. Mutations of the hydrophobic residues
      generally resulted in relatively small changes in the second-order electron
      transfer rate k(2) (Bronsted coefficient, alpha( )()= 0.15 +/- 0.05) indicating
      that the transition state for association occurs before short-range hydrophobic
      contacts are established. Larger changes in k(2), found in some cases, were
      attributed to a change in the second-order mechanism from a diffusion controlled
      regime to a rapidly reversible binding regime. The association constant, K(A), of
      the cyt and the rate of electron transfer from the bound cyt, k(e), were both
      decreased by mutation. Replacement of Tyr L162, Leu M191, or Val M192 by Ala
      decreased K(A) and k(e) by factors of 130, 10, 0.6, and 120, 9, 0.6,
      respectively. The largest changes were obtained by mutation of Tyr L162, showing
      that this residue plays a key role in both binding and electron transfer. The
      binding affinity, K(A), and electron-transfer rate, k(e) were strongly
      correlated, showing that changes of hydrophobic residues affect both binding and
      electron transfer. This correlation suggests that changes in distance across
      hydrophobic interprotein contacts have similar effects on both electron tunneling
      and binding interactions.

PMID- 14661962
TI  - Lack of negative charge in the E46Q mutant of photoactive yellow protein prevents
      partial unfolding of the blue-shifted intermediate.
AB  - The long-lived light-induced intermediate (pB) of the E46Q mutant (glutamic acid
      is replaced by glutamine at position 46) of photoactive yellow protein (PYP) has
      been investigated by NMR spectroscopy. The ground state of this mutant is very
      similar to that of wild-type PYP (WT), whereas the pB state, formed upon
      illumination, appears to be much more structured in E46Q than in WT. The
      differences are most striking in the N-terminal domain of the protein. In WT, the
      side-chain carboxylic group of E46 is known to donate its proton to the
      chromophore upon illumination. The absence of the carboxylic group near the
      chromophore in the E46Q mutant prohibits the formation of a negative charge at
      this position upon formation of pB. This prevents the partial unfolding of the
      mutant, as evidenced from NMR chemical shift comparison and proton/deuterium
      (H/D) exchange studies.

PMID- 14661963
TI  - Infrared spectroscopic and mutational studies on putidaredoxin-induced
      conformational changes in ferrous CO-P450cam.
AB  - Ferrous-carbon monoxide bound form of cytochrome P450cam (CO-P450cam) has two
      infrared (IR) CO stretching bands at 1940 and 1932 cm(-1). The former band is
      dominant (>95% in area) for CO-P450cam free of putidaredoxin (Pdx), while the
      latter band is dominant (>95% in area) in the complex of CO-P450cam with reduced
      Pdx. The binding of Pdx to CO-P450cam thus evokes a conformational change in the
      heme active site. To study the mechanism involved in the conformational change,
      surface amino acid residues Arg79, Arg109, and Arg112 in P450cam were replaced
      with Lys, Gln, and Met. IR spectroscopic and kinetic analyses of the mutants
      revealed that an enzyme that has a larger 1932 cm(-1) band area upon Pdx-binding
      has a larger catalytic activity. Examination of the crystal structures of R109K
      and R112K suggested that the interaction between the guanidium group of Arg112
      and Pdx is important for the conformational change. The mutations did not change
      a coupling ratio between the hydroxylation product and oxygen consumed. We
      interpret these findings to mean that the interaction of P450cam with Pdx through
      Arg112 enhances electron donation from the proximal ligand (Cys357) to the O-O
      bond of iron-bound O(2) and, possibly, promotes electron transfer from reduced
      Pdx to oxyP450cam, thereby facilitating the O-O bond splitting.

PMID- 14661964
TI  - Arg-14 loop of site 3 anemone toxins: effects of glycine replacement on toxin
      affinity.
AB  - Anthopleurin B (ApB) is a high-affinity sea anemone neurotoxin that interacts
      with voltage-sensitive sodium (Na(V)) channels, causing a delay in channel
      inactivation. The solution structures of all known anemone toxins having this
      activity include a poorly defined region encompassing ApB residues 8-17, which we
      call the Arg-14 loop. We propose that the inherent mobility of the Arg-14 loop is
      necessary for the toxins' ability to maintain a high-affinity channel complex
      throughout the continual conformational transitions experienced by the channel
      during its functional cycle. We have previously shown that Arg-12, located in
      this loop, and Leu-18, which is adjacent, are important for ApB activity. Here,
      we characterized the role of two glycines located within the loop (Gly-10 and Gly
      15) and an additional glycine positioned immediately C-terminal to it (Gly-20).
      We used site-directed replacement by alanine to assess the functional
      contribution to toxin binding of each of these residues singly and in
      combination. Gly-20 was found to be an essential toxin folding determinant; Gly
      10 and Gly-15 were important for determining toxin affinity. Compared to wild
      type toxin, the G10A and G15A toxins displayed significantly higher K(D) values
      for both cardiac (Na(V)1.5) and neuronal (Na(V)1.2) channels, although both
      demonstrated greater isoform discrimination for Na(V)1.5 than did wild-type ApB.
      For both G10A and G15A, significant Na(V) isoform differences were evident for on
      and off-rates, with the most dramatic effect of a single mutation being the 467
      fold reduction in the on-rate for G10A binding to Na(V)1.2, suggestive of a more
      accommodating binding site on Na(V)1.5 as compared to Na(V)1.2. Because alanine
      replacement of glycines is known to be associated with reduced backbone freedom,
      these results suggest an essential role for Arg-14 loop flexibility in toxin
      function, although a direct steric effect of the mutant methyl group cannot be
      excluded.

PMID- 14661965
TI  - Dimerization in aminergic G-protein-coupled receptors: application of a hidden
      site class model of evolution.
AB  - G-Protein-coupled receptors (GPCRs) are an important superfamily of transmembrane
      proteins involved in cellular communication. Recently, it has been shown that
      dimerization is a widely occurring phenomenon in the GPCR superfamily, with
      likely important physiological roles. Here we use a novel hidden-site class model
      of evolution as a sequence analysis tool to predict possible dimerization
      interfaces in GPCRs. This model aims to simulate the evolution of proteins at the
      amino acid level, allowing the analysis of their sequences in an explicitly
      evolutionary context. Applying this model to aminergic GPCR sequences, we first
      validate the general reasoning behind the model. We then use the model to perform
      a family specific analysis of GPCRs. Accounting for the family structure of these
      proteins, this approach detects different evolutionarily conserved and accessible
      patches on transmembrane (TM) helices 4-6 in different families. On the basis of
      these findings, we propose an experimentally testable dimerization mechanism,
      involving interactions among different combinations of these helices in different
      families of aminergic GPCRs.

PMID- 14661966
TI  - Deletion of the GPIdeAc gene alters the location and fate of
      glycosylphosphatidylinositol precursors in Trypanosoma brucei.
AB  - Glycosylphosphatidylinositol (GPI) membrane anchors are ubiquitous among the
      eukaryotes. In most organisms, the pathway of GPI biosynthesis involves inositol
      acylation and inositol deacylation as discrete steps at the beginning and end of
      the pathway, respectively. The bloodstream form of the protozoan parasite
      Trypanosoma brucei is unusual in that these reactions occur on multiple GPI
      intermediates and that it can express side chains of up to six galactose residues
      on its mature GPI anchors. An inositol deacylase gene, T. brucei GPIdeAc, has
      been identified. A null mutant was created and shown to be capable of expressing
      normal mature GPI anchors on its variant surface glycoprotein. Here, we show that
      the null mutant synthesizes galactosylated forms of the mature GPI precursor,
      glycolipid A, at an accelerated rate (2.8-fold compared to wild type). These free
      GPIs accumulate at the cell surface as metabolic end products. Using continuous
      and pulse-chase labeling experiments, we show that there are two pools of
      glycolipid A. Only one pool is competent for transfer to nascent variant surface
      glycoprotein and represents 38% of glycolipid A in wild-type cells. This pool
      rises to 75% of glycolipid A in the GPIdeAc null mutant. We present a model for
      the pathway of GPI biosynthesis in T. brucei that helps to explain the complex
      phenotype of the GPIdeAc null mutant.

PMID- 14661967
TI  - Generation of the R2 subunit of ribonucleotide reductase by intein chemistry:
      insertion of 3-nitrotyrosine at residue 356 as a probe of the radical initiation
      process.
AB  - Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of
      nucleoside diphosphates to deoxynucleoside diphosphates. The enzyme is composed
      of two subunits: R1 and R2. R1 contains the active site for nucleotide reduction
      and the allosteric effector sites that regulate the specificity and turnover
      rate. R2 contains the diferric-tyrosyl (Y(*)) radical cofactor that initiates
      nucleotide reduction by a putative long-range proton-coupled electron transfer
      (PCET) pathway over 35 A. This pathway is thought to involve specific amino acid
      radical intermediates (Y122 to W48 to Y356 within R2 to Y731 to Y730 to C439
      within R1). In an effort to study radical initiation, R2 (375 residues) has been
      synthesized semisynthetically. R2 (residues 1-353), attached to an intein and a
      chitin binding domain, was constructed, and the protein was expressed (construct
      1). This construct was then incubated with Fe(2+) and O(2) to generate the
      diferric-Y(*) cofactor, and the resulting protein was purified using a chitin
      affinity column. Incubation of construct 1 with 2-mercaptoethanesulfonic acid
      (MESNA) resulted in the MESNA thioester of R2 (1-353) (construct 2). A peptide
      containing residues 354-375 of R2 was generated using solid-phase peptide
      synthesis where 354, a serine in the wild-type (wt) R2, was replaced by a
      cysteine. Construct 2 and this peptide were ligated, and the resulting full
      length R2 was separated from truncated R2 by anion-exchange chromatography. The
      purified protein had a specific activity of 350 nmol min(-1) mg(-1), identical to
      the same protein generated by site-directed mutagenesis when normalized for Y(*).
      As a first step in studying the radical initiation by PCET, R2 was synthesized
      with Y356 replaced by 3-nitrotyrosine (NO(2)Y). The protein is inactive (specific
      activity 1 x 10(-4) that of wt-R2), which permitted a determination of the pK(a)
      of the NO(2)Y in the R1/R2 complex in the presence of substrate and effectors.
      Under all conditions, the pK(a) was minimally perturbed. This has important
      mechanistic implications for the radical initiation process.

PMID- 14661968
TI  - Characterization of tescalcin, a novel EF-hand protein with a single Ca2+-binding
      site: metal-binding properties, localization in tissues and cells, and effect on
      calcineurin.
AB  - The tescalcin gene is preferentially expressed during mouse testis
      differentiation. Here, we demonstrate that this gene encodes a 24 kDa Ca(2+)- and
      Mg(2+)-binding protein with one consensus EF-hand and three additional domains
      with EF-hand homology. Equilibrium dialysis with (45)Ca(2+) revealed that
      recombinant tescalcin binds approximately one Ca(2+) ion at physiological
      concentrations (pCa 4.5). The intrinsic tryptophan fluorescence of tescalcin was
      significantly reduced by Ca(2+), indicative of a conformational change. The
      apparent K(d) for Ca(2+) was 0.8 microM. A point mutation in the consensus EF
      hand (D123A) abolished (45)Ca(2+) binding and prevented the fluorescence
      quenching, demonstrating that the consensus EF-hand alone mediates the Ca(2+)
      induced conformational change. Tescalcin also binds Mg(2+) (K(d) 73 microM),
      resulting in a much smaller fluorescence decrease. In the presence of 1 mM
      Mg(2+), tescalcin's Ca(2+) affinity is shifted to 3.5 microM. These results
      illustrate that tescalcin should bind Mg(2+) constitutively in a quiescent cell,
      replacing it with Ca(2+) during stimulation. We also show that tescalcin is most
      abundant in adult mouse heart, brain, and stomach, as well as in HeLa and HL-60
      cells. Immunofluorescence microscopy revealed that tescalcin is present in the
      cytoplasm and nucleus, with concentration in membrane ruffles and lamellipodia in
      the presence of serum, where it colocalizes with the small guanosine
      triphosphatase Rac-1. Tescalcin shares sequence and functional homology with
      calcineurin-B homologous protein (CHP), and we found that tescalcin, like CHP,
      can inhibit the phosphatase activity of calcineurin A. Hence, tescalcin is a
      novel calcineurin B-like protein that binds a single Ca(2+) ion.

PMID- 14661969
TI  - Identification of sequences responsible for intracellular targeting and membrane
      binding of rat CYP2E1 in yeast.
AB  - The role of the hydrophobic NH(2)-terminal domain of rat CYP2E1 for intracellular
      targeting and membrane binding was investigated in Saccharomyces cerevisiae as a
      model system. Several different CYP2E1 variants with deletions and mutations were
      expressed in yeast, and their intracellular localization and membrane-binding
      properties were analyzed. We found that an amino acid stretch including the B
      helix from glycine 82 to asparagine 95 is responsible for mitochondrial
      association of CYP2E1 in yeast. Furthermore, we investigated the membrane-binding
      properties of the variants and concluded that the same region in the B-helix is
      responsible for membrane interactions of CYP2E1 by electrostatic interactions. A
      soluble variant of CYP2E1 lacking the first 82 amino acids and containing leucine
      to aspartate amino acid exchanges at positions 90 and 91, which disrupted the
      amphipathic nature of the B-helix, was expressed at relatively high levels in the
      yeast and was found to be catalytically active toward chlorzoxazone in cumene
      hydroperoxide-supported reactions. We suggest that these amino acid changes at
      positions 90 and 91 abolish the electrostatic interaction between the negatively
      charged membrane and the positively charged B-helix, thereby producing a soluble
      product.

PMID- 14661970
TI  - Transbilayer lipid diffusion promoted by Bax: implications for apoptosis.
AB  - It is known that the proapoptotic protein Bax facilitates the formation of pores
      in bilayers, resulting in the release of proteins from the intermitochondrial
      space. We demonstrate that another consequence of the interaction of Bax with
      membranes is an increase in the rate of lipid transbilayer diffusion. We use two
      independent assays for transbilayer diffusion, one involving the formation of
      asymmetric liposomes by placing a pyrene-labeled lipid into the outer monolayer
      of preformed vesicles and another assay based on the initial preparation of
      liposomes having an asymmetric transbilayer distribution of lipids. With both
      methods we find that oligomeric BaxDeltaC or full-length Bax in the presence of
      tBid, but not monomeric full-length Bax, strongly promotes the rate of
      transbilayer diffusion. Although biological membranes exhibit rates of lipid
      transbilayer diffusion of minutes or less, they are able to maintain an
      asymmetric distribution of lipids across the bilayer. In the case of
      mitochondria, cardiolipin is sequestered on the inner leaflet of the inner
      mitochondrial membrane. However, during apoptosis this lipid translocates to the
      outer surface of the outer mitochondrial membrane. This phenomenon must involve
      an increase in the rate of transbilayer diffusion. The results of the present
      paper demonstrate that an activated form of Bax can cause this increased rate.

PMID- 14661971
TI  - Sterol carrier protein-2 selectively alters lipid composition and cholesterol
      dynamics of caveolae/lipid raft vs nonraft domains in L-cell fibroblast plasma
      membranes.
AB  - Although the functional significance of caveolae/lipid rafts in cellular
      signaling and cholesterol transfer is increasingly recognized, almost nothing is
      known regarding the lipids, cholesterol dynamics, and factors regulating these
      properties in caveolae/lipid rafts as opposed to nonlipid raft domains of the
      plasma membrane. The present findings demonstrate the utility of con-A affinity
      chromatography for simultaneous isolation of caveolae/lipid raft and nonlipid
      raft domains from plasma membranes of L-cell fibroblasts. These domains differed
      markedly in both protein and lipid constituents. Although caveolae/lipid rafts
      were enriched in total lipid, cholesterol, and phospholipid as well as other
      markers for these domains, the cholesterol/phospholipid ratio of caveolae/lipid
      rafts did not differ from that of nonlipid rafts. Nevertheless, spontaneous
      sterol transfer was 7-12-fold faster from caveolae/lipid raft than nonlipid raft
      domains of the plasma membrane. This was largely due to the near absence of
      exchangeable sterol in the nonlipid rafts. SCP-2 dramatically and selectively
      enhanced sterol transfer from caveolae/lipid rafts, but not from nonlipid rafts.
      Finally, overexpression of SCP-2 significantly altered the sterol dynamics of
      caveolae/lipid rafts to facilitate retention of cholesterol within the cell.
      These results established for the first time that (i) caveolae/lipid rafts,
      rather than the nonlipid raft domains, contain significant levels of rapidly
      transferable sterol, consistent with their role in spontaneous sterol transfer
      from and through the plasma membrane, and (ii) SCP-2 selectively regulates how
      caveolae/lipid rafts, but not nonlipid raft domains, mediate cholesterol
      trafficking through the plasma membrane.

PMID- 14661972
TI  - Quaternary structure of Dictyostelium discoideum nucleoside diphosphate kinase
      counteracts the tendency of monomers to form a molten globule.
AB  - Multimeric enzymes that lose their quaternary structure often cease to be
      catalytically competent. In these cases, conformational stability depends on
      contacts between subunits, and minor mutations affecting the surface of the
      monomers may affect overall stability. This effect may be sensitive to pH,
      temperature, or solvent composition. We investigated the role of oligomeric
      structure in protein stability by heat and chemical denaturation of hexameric
      nucleoside diphosphate kinase from Dictyostelium discoideum and its P105G mutant
      over a wide range of pH. The wild-type enzyme has been reported to unfold without
      prior dissociation into monomers, whereas monomer unfolding follows dissociation
      for the P105G mutant (Giartosio et al. (1996) J. Biol. Chem. 271, 17845-51). We
      show here that these features are also preserved at alkaline pH, with the wild
      type enzyme always hexameric at room temperature whereas the mutant dissociates
      into monomers at pH >or=10. In acidic conditions (pH <or=6), even in the absence
      of denaturant, the predominant species for both proteins is an intermediate
      monomeric form with the characteristics of a molten globule: disordered tertiary
      native structure but preserved secondary structure. Monomers therefore seem to
      have a low intrinsic stability, which is overcome by the conformational
      organization in the oligomeric structure.

PMID- 14661973
TI  - Stabilization of partially folded states of cytochrome c in aqueous surfactant:
      effects of ionic and hydrophobic interactions.
AB  - The interaction of submicellar concentrations of sodium dodecyl sulfate (SDS)
      with horse heart cytochrome c has been found to stabilize two spectroscopically
      distinct partially folded intermediates at pH 7. The first intermediate is formed
      by the interaction of SDS with native cytochrome c, and this intermediate retains
      the majority of the secondary structure while the tertiary structure of the
      protein is lost. The unfolding of this intermediate with urea leads to the
      formation of a second intermediate, which is also formed on refolding of the
      unfolded protein (unfolded by urea) by SDS. The second intermediate retains about
      50% of the native secondary structure with no tertiary structure of the protein.
      The second intermediate was found to be absent at low pH. While induction of
      helical structure of a protein by SDS in the native condition has been reported
      earlier, this is possibly the first report of the refolding of a protein in a
      strongly denaturing condition (in the presence of 10 M urea). The relative
      contributions of the hydrophobic and the electrostatic interactions of the
      surfactants with cytochrome c have been determined from the formation of the
      molten globule species from the acid-induced unfolded protein in the presence of
      SDS or lauryl maltoside.

PMID- 14661974
TI  - Neisseria gonorrhoeae penicillin-binding protein 3 exhibits exceptionally high
      carboxypeptidase and beta-lactam binding activities.
AB  - A soluble form of penicillin-binding protein 3 (PBP 3) from Neisseria gonorrhoeae
      was expressed and purified from Escherichia coli and characterized for its
      interaction with beta-lactam antibiotics, its catalytic properties with peptide
      and peptidoglycan substrates, and its role in cell viability and morphology. PBP
      3 had an unusually high k(2)/K' value relative to other PBPs for acylation with
      penicillin (7.7 x 10(5) M(-1) s(-1)) at pH 8.5 at 25 degrees C and hydrolyzed
      bound antibiotic very slowly (k(3) < 4.6 x 10(-5) s(-1), t(1/2) > 230 min). PBP 3
      also demonstrated exceptionally high carboxypeptidase activity with a k(cat) of
      580 s(-1) and a k(cat)/K(m) of 1.8 x 10(5) M(-1) s(-1) with the substrate
      N(alpha)-Boc-N(epsilon)-Cbz-L-Lys-D-Ala-D-Ala. This is the highest k(cat) value
      yet reported for a PBP or other serine peptidases. Activity against a
      approximately D-Ala-D-Lac peptide substrate was approximately 2-fold lower than
      against the analogous approximately D-Ala-D-Ala peptide substrate, indicating
      that deacylation is rate determining for both amide and ester hydrolysis. The pH
      dependence profiles of both carboxypeptidase activity and beta-lactam acylation
      were bell-shaped with maximal activity at pH 8.0-8.5. PBP 3 displayed weak
      transpeptidase activity in a model transpeptidase reaction but was active as an
      endopeptidase, cleaving dimeric peptide cross-links. Deletion of PBP 3 alone had
      little effect on viability, growth rate, and morphology of N. gonorrhoeae,
      although deletion of both PBP 3 and PBP 4, the other low-molecular-mass PBP in N.
      gonorrhoeae, resulted in a decreased growth rate and marked morphological
      abnormalities.

PMID- 14661975
TI  - Temperature-dependent, irreversible formation of amyloid fibrils by a soluble
      human ataxin-3 carrying a moderately expanded polyglutamine stretch (Q36).
AB  - The protein ataxin-3 is responsible for Machado-Joseph disease/spinocerebellar
      ataxia type 3, a neurodegenerative disorder caused by the presence of an expanded
      polyglutamine tract. A previous investigation [Bevivino, A. E., and Loll, P. J.
      (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 11955-11960] showed that a nonexpanded
      ataxin-3 (Q27) was fully soluble, whereas an expanded form (Q78) gave rise to
      amyloid fibrils. Here, we report investigations on three forms of ataxin-3 (i.e.,
      human nonexpanded (Q26), moderately expanded (Q36) ataxins-3, and the murine
      protein (Q6)). Far-UV circular dichroism spectra at room temperature were
      substantially similar, with a relatively high helical content. On heating to 96
      degrees C, human Q26 and murine proteins did not display large structural
      changes, nor did they undergo any precipitation, which highlights their amazing
      heat-resistance. In contrast, human Q36 ataxin-3 underwent a progressive increase
      in the beta-sheet and a concomitant decrease in helical content when the
      temperature was shifted from 37 to 80 degrees C, followed by the irreversible
      formation of aggregates above 80 degrees C. They were shown to consist of amyloid
      fibrils, as supported by both electron microscopy images and the typical spectral
      shift displayed by Congo red when it was added to the protein at growing
      temperatures. We also found that protein precipitation could be prevented by
      mixing the dye with Q36 ataxin-3 prior to heating, which also confirms that the
      precipitates do represent authentic amyloid fibrils. In contrast, other compounds
      structurally related to Congo red did not exert significant effects. Our
      observations suggest that the temperature of the observed transition is inversely
      related to the length of the expansion. Finally, we suggest that
      antiamyloidogenic compounds might be selected on the basis of their ability to
      block or retard human Q36 ataxin-3 precipitation on heat-treatment.

PMID- 14661976
TI  - MuA transposase separates DNA sequence recognition from catalysis.
AB  - Confronted with thousands of potential DNA substrates, a site-specific enzyme
      must restrict itself to the correct DNA sequence. The MuA transposase protein
      performs site-specific DNA cleavage and joining reactions, resulting in DNA
      transposition-a specialized form of genetic recombination. To determine how
      sequence information is used to restrict transposition to the proper DNA sites,
      we performed kinetic analyses of transposition with DNA substrates containing
      either wild-type transposon sequences or sequences carrying mutations in specific
      DNA recognition modules. As expected, mutations near the DNA cleavage site reduce
      the rate of cleavage; the observed effect is about 10-fold. In contrast,
      mutations within the MuA recognition sequences do not directly affect the DNA
      cleavage or joining steps of transposition. It is well established that the
      recognition sequences are necessary for assembly of stable, multimeric MuA-DNA
      complexes, and we find that recognition site mutations severely reduce both the
      extent and the rate of this assembly process. Yet if the MuA-DNA complexes are
      preassembled, the first-order rate constants for both DNA cleavage and DNA strand
      transfer (the joining reaction) are unaffected by the mutations. Furthermore,
      most of the mutant DNA molecules that are cleaved also complete DNA strand
      transfer. We conclude that the sequence-specific contacts within the recognition
      sites contribute energetically to complex assembly, but not directly to
      catalysis. These results contrast with studies of more orthodox enzymes, such as
      EcoRI and some other type II restriction enzymes. We propose that the strategy
      employed by MuA may serve as an example for how recombinases and modular
      restriction enzymes solve the DNA specificity problem, in that they, too, may
      separate substrate recognition from catalysis.

PMID- 14661977
TI  - Staphylococcus aureus fibronectin-binding protein serves as a substrate for
      coagulation factor XIIIa: evidence for factor XIIIa-catalyzed covalent cross
      linking to fibronectin and fibrin.
AB  - In this study, we have investigated the interactions of a Staphylococcal
      recombinant fibronectin-binding protein A (rFnbA) with fibronectin, fibrinogen,
      and fibrin. Using analytical size-exclusion chromatography, we evaluated the
      stoichiometry of reversible binding of FnbA to fibronectin and demonstrated that,
      in solution, it can accommodate at least two molecules of fibronectin. Results of
      ELISA experiments demonstrated that rFnbA binds with equally high affinity to
      both immobilized fibrinogen and fibrin. When included into a thrombin-induced
      fibrin polymerization reaction, rFnbA strongly inhibited fibrin assembly in a
      dose-dependent manner. In this study, we have shown that rFnbA can act as a
      substrate for coagulation factor XIIIa. Factor XIIIa catalyzes the incorporation
      of amine donor (dansylacadaverine) and amine acceptor (peptide patterned on the N
      terminal sequence of fibronectin) synthetic probes into rFnbA, suggesting that it
      serves as a bifunctional substrate containing reactive glutamine and lysine
      residues. We have demonstrated that the reversible complex formed by rFnbA and
      fibronectin or rFnbA and fibrin is covalently stabilized by the transglutaminase
      action of factor XIIIa. Incubation of rFnbA in the presence of either of its
      ligands and factor XIIIa results in the introduction of intermolecular epsilon
      (gamma-glutamyl)lysine isopeptide bond(s) and the formation of high molecular
      mass heteropolymers. These findings suggest a novel mechanism by which pathogenic
      Staphylococcus aureus may utilize the transglutaminase activity of factor XIIIa
      for attachment to soluble proteins, cell surfaces, and matrixes.

PMID- 14661978
TI  - Cobalamin-dependent methionine synthase: probing the role of the axial base in
      catalysis of methyl transfer between methyltetrahydrofolate and exogenous
      cob(I)alamin or cob(I)inamide.
AB  - Cobalamin-dependent methionine synthase (MetH) catalyzes the transfer of methyl
      groups between methyltetrahydrofolate (CH(3)-H(4)folate) and homocysteine, with
      the enzyme-bound cobalamin serving as an intermediary in the methyl transfers. An
      MetH fragment comprising residues 2-649 contains modules that bind and activate
      CH(3)-H(4)folate and homocysteine and catalyze methyl transfers to and from
      exogenous cobalamin. Comparison of the rates of reaction of cobalamin, which
      contains a dimethylbenzimidazole nucleotide coordinated to the cobalt in the
      lower axial position, and cobinamide, which lacks the dimethylbenzimidazole
      nucleotide, allows assessment of the degree of stabilization the
      dimethylbenzimidazole base provides for methyl transfer between CH(3)-H(4)folate
      bound to MetH(2-649) and exogenous cob(I)alamin. When the reactions of
      cob(I)alamin or cob(I)inamide with CH(3)-H(4)folate are compared, the observed
      second-order rate constants are 2.7-fold faster for cob(I)alamin; in the reverse
      direction, methylcobinamide reacts 35-fold faster than methylcobalamin with
      enzyme-bound tetrahydrofolate. These measurements can be used to estimate the
      influence of the dimethylbenzimidazole ligand on both the thermodynamics and
      kinetics of methyl transfer between methyltetrahydrofolate and cob(I)alamin or
      cob(I)inamide. The free energy change for methyl transfer from CH(3)-H(4)folate
      to cob(I)alamin is 2.8 kcal more favorable than that for methyl transfer to
      cob(I)inamide. Dimethylbenzimidazole contributes approximately 0.6 kcal/mol of
      stabilization for the forward reaction and approximately 2.2 kcal/mol of
      destabilization for the reverse reaction. Binding of methylcobalamin to full
      length methionine synthase is accompanied by ligand substitution, and switching
      between "base-on" and "base-off" states of the cofactor has been demonstrated
      [Bandarian, V., et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 8156-8163]. The
      present results disfavor a major role for such switching in catalysis of methyl
      transfer, and are consistent with the hypothesis that the primary role of the
      ligand triad in methionine synthase is controlling the distribution of enzyme
      conformations during catalysis.

PMID- 14661979
TI  - Membrane topology of guinea pig cytochrome P450 17 alpha revealed by a
      combination of chemical modifications and mass spectrometry.
AB  - Cytochrome P450s in endoplasmic reticulum membranes function in the hydroxylation
      of exogenous and endogenous hydrophobic substrates concentrated in the membranes.
      The reactions require electron supplies from NADPH-cytochrome P450 reductase in
      the same membranes. The membranes play important roles in the reaction of
      cytochrome P450. The membrane topology of guinea pig P450 17alpha was
      investigated on the basis of the differences in reactivity to hydrophilic
      chemical modification reagents between those in the detergent-solubilized state
      and proteoliposomes. Recombinant guinea pig cytochrome P450 17alpha was purified
      from Escherichia coli and incorporated into liposome membranes. Lysine residues
      in the detergent-solubilized P450 17alpha and in the proteoliposomes were
      acetylated with acetic anhydride at pH 9.0, and the acidic amino acid residues
      were conjugated with glycinamide at pH 5.0 by the aid of a coupling reagent, 1
      ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The modifications were
      performed under conditions where the denatured form, P420, was not induced. The
      modified P450 17alpha's were digested by trypsin, and the molecular weights of
      the peptide fragments were determined by MALDI-TOF mass spectrometry. From the
      increase in the molecular weights of the peptides, the positions of modifications
      could be deduced. In the detergent-solubilized state, 11 lysine residues and 7
      acidic amino acid residues were modified, among which lysine residues at
      positions 29, 59, 490, and 492 and acidic residues at 211, 212, and/or 216 were
      not modified in the proteoliposomes. Both the N- and C-terminal domains and the
      putative F-G loop were concluded to be in or near the membrane-binding domains of
      P450 17alpha.

PMID- 14661980
TI  - "Nonclassical" secretion of annexin A2 to the lumenal side of the enterocyte
      brush border membrane.
AB  - Annexin A2 is a member of the annexin family of Ca(2+)-dependent lipid binding
      proteins and believed to be engaged in membrane transport processes in a number
      of cell types. In small intestinal enterocytes, we localized annexin A2 to the
      brush border region, where it was found mainly on the lumenal side of the
      microvilli, showing an apical secretion by a "nonclassical" mechanism. In
      addition, annexin A2 was associated with surface-connected, deep apical tubules
      in the apical terminal web region and with an underlying pleiomorphic, tubulo
      vesicular compartment (subapical compartment/multivesicular bodies). By
      subcellular fractionation, the 36 kDa full-length form of annexin A2 was
      approximately equally distributed between the Mg(2+)-precipitated fraction
      (containing intracellular and basolateral membranes) and the microvillar membrane
      fraction. In addition, a 33 kDa molecular form of annexin A2 was seen in the
      latter fraction that could be generated from the full-length annexin A2 by
      digestion with trypsin. Taken together, the results suggest that annexin A2 acts
      in exocytic apical membrane trafficking and is proteolytically cleaved in situ by
      pancreatic proteinases once it has become externalized to the lumenal side of the
      brush border membrane. On the basis of its well-known membrane fusogenic
      properties, we propose a model for the nonclassical membrane translocation of
      annexin A2.

PMID- 14661981
TI  - Peptide-induced formation of cholesterol-rich domains.
AB  - The peptide N-acetyl-LWYIK-amide causes the reorganization of bilayers of
      phosphatidylcholine and cholesterol to produce domains enriched in cholesterol.
      At a cholesterol mol fraction of 0.5, addition of N-acetyl-LWYIK-amide results in
      the formation of cholesterol crystallites. Addition of this peptide to mixtures
      of 1-stearoyl-2-oleoylphosphatidylcholine with lower mol fractions of cholesterol
      results in an increase in the enthalpy of the chain melting transition of the
      phospholipid, indicating the depletion of cholesterol from a domain in the
      membrane. The peptide binds to membranes both with and without cholesterol.
      However, (1)H magic-angle spinning (MAS) nuclear Overhauser effect spectroscopy
      (NOESY) indicates that in the presence of cholesterol the peptide has greater
      penetration into the bilayer. (13)C MAS NMR indicates that the peptide has
      stronger interactions with the A ring of cholesterol than it does with the
      interior of the bilayer. These results are in contrast with those of another
      peptide, N-acetyl-KYWFYR-amide, which does not promote the formation of
      cholesterol crystallites and does not show preferential interaction with
      cholesterol by NMR. Therefore, cholesterol can promote the insertion of N-acetyl
      LWYIK-amide into a membrane and this peptide will sequester cholesterol into
      domains. These properties help to explain the observation that this sequence is
      found to be important in causing the fusion protein of human immunodeficiency
      virus (HIV) to sequester into raft domains in biological membranes.

PMID- 14661982
TI  - Salt bridges do not stabilize polyproline II helices.
AB  - Interactions between side chains, and in particular salt bridges, have been shown
      to be important in the stabilization of secondary structure. Here we investigate
      the contribution of a salt bridge formed between a lysine and a glutamate to the
      polyproline II (P(II)) helical content of proline-rich peptides. Since this
      structure has precisely three residues per turn, charged residues spaced three
      residues apart are on the same side of the helix and are best situated to
      interact. By contrast, computer simulations show that charged residues spaced
      four residues apart are both too far apart to interact strongly and are oriented
      such that interactions are unlikely. We have measured the P(II) content of
      peptides containing a lysine and glutamate pair spaced three or four residues
      apart using circular dichroism spectroscopy. Somewhat surprisingly we find that
      the P(II) content is insensitive to both the spacing and the pH. These findings
      indicate that i --> i + 3 salt bridges do not stabilize the P(II) helical
      conformation. The implications of these observations for both P(II) helix
      formation and denatured protein conformations are discussed.

PMID- 14661983
TI  - Interstrand cross-linking of DNA by FK317 and its deacetylated metabolites
      FR70496 and FR157471.
AB  - FR900482 (1) and FR66979 (2) are structurally novel natural products isolated by
      Fujisawa in 1987 and have been shown to be highly potent antitumor antibiotics
      structurally related to the mitomycins. Studies on the mode of action have
      established that these new agents form covalent DNA interstrand cross-links both
      in vitro and in vivo as a result of the reactive mitosene intermediate generated
      upon bioreductive activation. Semisynthetic analogues such as FK973 (3) and FK317
      (4) were developed in the search for potentially superior clinical candidates.
      Although FK317 has been shown to be a potent compound, to date no direct evidence
      of DNA interstrand cross-link sequence specificity has been reported. In this
      study, DNA interstrand cross-links were generated by treatment of a synthetic
      duplex DNA substrate with FK317 (4) and its deacetylated metabolites FR70496 (5)
      and FR157471 (6). Analysis by gel electrophoresis revealed the formation of
      orientation isomers displaying electrophoretic mobility vastly greater than the
      mobilities of those generated from FR900482 (1). Despite these differences, it
      was established by Fe(II)-EDTA footprinting that FK317 (4) as well as 5 and 6
      forms DNA interstrand cross-links within the expected 5'CpG3' step, clearly
      demonstrating that the phenolic hydrogen in 1 and 2 is not a prerequisite for
      efficient DNA interstrand cross-linking by the FR class of compounds.

PMID- 14661984
TI  - Structural analysis of the alpha N-terminal region of erythroid and nonerythroid
      spectrins by small-angle X-ray scattering.
AB  - We used SpalphaI-1-156 peptide, a well-characterized model peptide of the alphaN
      terminal region of erythrocyte spectrin, and SpalphaII-1-149, an alphaII brain
      spectrin model peptide similar in sequence to SpalphaI-1-156, to study their
      association affinities with a betaI-spectrin peptide, SpbetaI-1898-2083, by
      isothermal titration calorimetry. We also determined their conformational
      flexibilities in solution by small-angle X-ray scattering (SAXS) methods. These
      two peptides exhibit sequence homology and could be expected to exhibit similar
      association affinities with beta-spectrin. However, our studies show that the
      affinity of SpalphaII-1-149 with SpbetaI-1898-2083 is much higher than that of
      SpalphaI-1-156. Our SAXS findings also indicate a significantly more extended
      conformation for SpalphaII-1-149 than for SpalphaI-1-156. The radius of gyration
      values obtained by two different analyses of SAXS data and by molecular modeling
      all show a value of about 25 A for SpalphaI-1-156 and of about 30 A for SpalphaII
      1-149, despite the fact that SpalphaI-1-156 has seven amino acid residues more
      than SpalphaII-1-149. For SpalphaI-1-156, the SAXS results are consistent with a
      flexible junction between helix C' and the triple helical bundle that allows
      multiple orientations between these two structural elements, in good agreement
      with our published NMR analysis. The SAXS findings for SpalphaII-1-149 support
      the hypothesis that this junction region is rigid (and probably helical) for
      alphaII brain spectrin. The nature of the junction region, from one extreme as a
      random coil (conformationally mobile) segment in alphaI to another extreme as a
      rigid segment in alphaII, determines the orientation of helix C' relative to the
      first structural domain. We suggest that this particular junction region in alpha
      spectrin plays a major role in modulating its association affinity with beta
      spectrins, and thus regulates spectrin tetramer levels. We also note that these
      are the first conformational studies of brain spectrin.

PMID- 14661985
TI  - Pharmacological treatment of severe psychiatric disorders in the developing world
      : lessons from India.
AB  - Severe psychiatric disorders (schizophrenia, bipolar disorder and major
      depressive disorder) cause much morbidity and disability in developing countries.
      Most of the evidence on the efficacy and effectiveness of drug treatments for
      these disorders is based on trials conducted in Western countries. Cultural,
      biological and health system factors may profoundly influence the applicability
      of such evidence in developing countries. Attitudes towards, and concepts about,
      psychiatric disorders vary across cultures, and these may influence the
      acceptability of drug treatments. Genetic and environmental factors may lead to
      variations in the pharmacodynamics and pharmacokinetics of psychotropic drugs
      across ethnic groups. This may explain why lower doses of psychotropic drugs tend
      to be used for non-Caucasian patients. There is a dearth of mental health
      professionals and care facilities in developing countries, especially in rural
      areas. Epidemiological studies show that, despite this lack of services, the
      outcome of schizophrenia is favourable in developing countries. This suggests
      that cultural, genetic or environmental factors may play as much of a role in
      influencing outcome as access to antipsychotic treatment. Regional drug policies
      may influence the availability and cost of psychotropic drugs. In particular, the
      Indian experience, where drugs are manufactured by several local pharmaceutical
      firms, thus bringing their cost down, may represent a unique deregulated drug
      industry. However, the impending impact of the Trade-Related Aspects of
      Intellectual Property Rights (TRIPS) agreement, with the strict enforcement of
      patent laws, will almost certainly lead to a rise in drug costs in the coming
      years. This may influence the choice and cost effectiveness of various drugs. The
      implications of these cross-cultural variations for policy and practice are the
      need to ensure a reliable supply of affordable psychotropic drugs in developing
      countries, trained healthcare professionals to use these drugs rationally, a
      concerted advocacy campaign to exclude drugs for severe psychiatric disorders
      from patent protection, and the development of psychosocial programmes to improve
      global outcomes.

PMID- 14661986
TI  - Clinical potential of omega-3 fatty acids in the treatment of schizophrenia.
AB  - The phospholipids in the neuronal membranes of the brain are rich in highly
      unsaturated essential fatty acids (EFAs). It has been hypothesised that
      abnormalities of phospholipid metabolism are present in patients with
      schizophrenia and that the EFAs omega-3 polyunsaturated fatty acids, and
      eicosapentaenoic acid (EPA) in particular, may have a role in treating this
      illness. Considerable preclinical and clinical evidence provides support for this
      proposal. An epidemiological study reported a better outcome for patients with
      schizophrenia in countries where the diet is rich in unsaturated fatty acids.
      Evidence of abnormalities of EFAs has been found in erythrocyte membranes and
      cultured skin fibroblasts of patients with schizophrenia, and abnormal retinal
      function and niacin skin flush tests (markers of omega-3 polyunsaturated fatty
      acid depletion) have also been reported. Case reports and an open-label clinical
      trial reported efficacy for EPA in schizophrenia. Four randomised, controlled
      trials of EPA versus placebo as supplemental medication have now been reported.
      Two of these trials showed significant benefit with EPA on the positive and
      negative symptom scale total scores, whereas the other two did not show any
      effects on this primary efficacy measure. One study also reported a beneficial
      effect on dyskinesia. In the only published trial in which EPA was used as
      monotherapy versus placebo in schizophrenia, some evidence was found to suggest
      antipsychotic activity. Taken together, there is considerable evidence to suggest
      abnormalities of EFAs in cell membranes of patients with schizophrenia, and there
      is preliminary evidence that EPA is an effective adjunct to antipsychotics.

PMID- 14661987
TI  - Poststroke motor dysfunction and spasticity: novel pharmacological and physical
      treatment strategies.
AB  - Following stroke, approximately 90% of patients experience persistent
      neurological motor deficits that lead to disability and handicap. Both
      pharmacological and physical treatment strategies for motor rehabilitation may be
      considered. In terms of pharmacological treatment, drugs that may potentially
      promote motor recovery when added to a regimen of physical therapy include the
      stimulants amphetamine and methylphenidate, as well as levodopa and fluoxetine.
      Botulinum toxin A has proven effective and well tolerated in several placebo
      controlled trials for the treatment of focal upper and lower limb spasticity,
      although it has not been shown to improve motor function. The focal injection of
      botulinum toxin A inhibits the release of acetylcholine into the synaptic cleft,
      resulting in a reversible paresis of the muscles relevant for the spastic
      deformity. Other drugs, such as benzodiazepines, antiepileptic drugs and
      antipsychotics, may have detrimental effects on motor function and should be
      avoided, if possible. With respect to physical strategies, modern concepts of
      motor learning favour a task-specific repetitive approach that induces skill
      acquisition relevant to the patient's daily life. Constrained-induced movement
      therapy based on the concept of learned non-use, electromyography-triggered
      electrical stimulation of the wrist muscles, robot-assisted motor rehabilitation
      to increase therapy intensity and bilateral practice to facilitate the movement
      of the paretic extremity are examples in upper limb rehabilitation. Lower limb
      rehabilitation has been enriched by treadmill training with partial bodyweight
      support, enabling the practice of up to 1000 steps per session; automated gait
      rehabilitation to relieve the strenuous effort required of the therapist; and
      rhythmic auditory stimulation, applying individually adjusted music to improve
      walking speed and symmetry.

PMID- 14661988
TI  - Treatment of recurrent depression: a sequential psychotherapeutic and
      psychopharmacological approach.
AB  - The chronic and recurrent nature of major depressive disorder is receiving
      increasing attention. Approximately eight of ten people experiencing a major
      depressive episode will have at least one more episode during their lifetime,
      i.e. recurrent major depressive disorder. In the 1990s, prolonged or lifelong
      pharmacotherapy emerged as the main therapeutic tool for preventing relapses of
      depression. This therapeutic approach is based on the effectiveness of
      antidepressant drugs compared with placebo in decreasing relapse risk and on the
      improved tolerability profile of the newer antidepressants compared with their
      older counterparts. However, outcome after discontinuation of antidepressant
      therapy does not seem to be affected by the duration of administration. Loss of
      clinical effects, despite adequate compliance, has also emerged as a vexing
      clinical problem. The use of intermittent pharmacotherapy with follow-up visits
      is an alternative therapeutic option. This leaves patients with periods free of
      drugs and adverse effects and takes into account that a high proportion of
      patients would discontinue the antidepressant anyway. However, the problems of
      resistance (that a drug treatment may be associated with a diminished chance of
      response in subsequent treatments in those patients whose symptoms successfully
      responded to it but who discontinued it) and of discontinuation syndromes are
      substantial disadvantages of this therapeutic approach. In recent years, several
      controlled trials have suggested that sequential use of pharmacotherapy in the
      treatment of the acute depressive episode and psychotherapy in its residual phase
      may improve long-term outcome. Patients, however, need to be motivated for
      psychotherapy, and skilled therapists have to be available. Despite an impressive
      amount of research into the treatment of depression, there is still a paucity of
      studies addressing the specific problems that prevention of recurrent depression
      entails. It is important to discuss with the patient the various therapeutic
      options and to adapt strategies to the specific needs of patients.

PMID- 14661989
TI  - Treatment of recurrent depression: an alternate viewpoint.

PMID- 14661990
TI  - High-risk localised prostate cancer: multimodal treatment strategies combining
      neoadjuvant hormonal therapy and/or chemotherapy with radical prostatectomy.
AB  - For patients with newly diagnosed prostate cancer, clinical tumour stage, Gleason
      score of the diagnostic biopsy specimen and serum prostate-specific antigen (PSA)
      level can be combined to identify a group of men at increased risk of treatment
      failure after radiotherapy or radical prostatectomy. For these high-risk, but
      still clinically localised prostate cancers, multimodal treatment strategies may
      result in improved cancer control outcomes. Indeed, in the setting of clinical
      stage T3 - T4 tumours, the combination of radiotherapy followed by hormonal
      therapy has improved patient survival. The benefits of adjuvant or neoadjuvant
      hormonal and/or chemotherapy followed by radical prostatectomy in this setting
      are unclear, but are the subject of ongoing or planned Phase III clinical trials.
      These studies will help define the role of multimodal treatment strategies in
      this high-risk patient population.

PMID- 14661991
TI  - Ketolides: an emerging treatment for macrolide-resistant respiratory infections,
      focusing on S. pneumoniae.
AB  - Resistance to antibiotics in community acquired respiratory infections is
      increasing worldwide. Resistance to the macrolides can be class-specific, as in
      efflux or ribosomal mutations, or, in the case of erythromycin ribosomal
      methylase (erm)-mediated resistance, may generate cross-resistance to other
      related classes. The ketolides are a new subclass of macrolides specifically
      designed to combat macrolide-resistant respiratory pathogens. X-ray
      crystallography indicates that ketolides bind to a secondary region in domain II
      of the 23S rRNA subunit, resulting in an improved structure-activity
      relationship. Telithromycin and cethromycin (formerly ABT-773) are the two most
      clinically advanced ketolides, exhibiting greater activity towards both typical
      and atypical respiratory pathogens. As a subclass of macrolides, ketolides
      demonstrate potent activity against most macrolide-resistant streptococci,
      including ermB- and macrolide efflux (mef)A-positive Streptococcus pneumoniae.
      Their pharmacokinetics display a long half-life as well as extensive tissue
      distribution and uptake into respiratory tissues and fluids, allowing for once
      daily dosing. Clinical trials focusing on respiratory infections indicate
      bacteriological and clinical cure rates similar to comparators, even in patients
      infected with macrolide-resistant strains.

PMID- 14661992
TI  - Emerging therapies for graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD) and chronic GVHD remain the major barriers
      to successful haematopoietic cell transplantation. The induction of GVHD may be
      divided into three phases: (i) recipient conditioning, (ii) donor T cell
      activation, and (iii) effector cells mediating GVHD. Standard agents and agents
      under development to prevent and treat GVHD are discussed. The various
      pharmacological agents impact on different phases of the GVHD cascade. Sirolimus
      is a new immunophilin binding agent that appears to be synergistic with
      tacrolimus and cyclosporin. It also seems to promote allograft tolerance.
      Mycophenolate mofetil (MMF) is an antimetabolite that is currently under study
      for prophylaxis and treatment of acute and chronic GVHD; results are encouraging.
      Other agents such as the purine analogue pentostatin and the monoclonal
      antibodies alemtuzumab, daclizumab and infliximab are discussed at length within
      the GVHD context. The most effective approach to GVHD prevention will likely be a
      combination regimen where the three phases of the GVHD cascade are disrupted.
      Once GVHD has occurred, all three phases of the cascade are activated.
      Developments of combination therapy for the treatment of both acute and chronic
      GVHD will likely yield better results than monotherapy. The numerous new
      treatment modalities presented should improve the outlook for acute and chronic
      GVHD.

PMID- 14661993
TI  - Emerging biotherapies for inflammatory bowel disease.
AB  - The immunological and genetic pathogeneses of inflammatory bowel disease (IBD)
      have been well studied, but not well elucidated in recent years. Accordingly, the
      pharmacological treatment of IBD is focusing upon the individual pathologic step
      (targeting therapy). It has recently become apparent that new drugs such as
      biological immunomodulating agents and anti-inflammatory cytokines have better
      short-term effects in some respects than conventional drugs, and they could
      change the treatment strategy of IBDs in the near future. Many options are now
      available to treat IBD. The choice depends on the type of IBD, the location of
      inflammation and the severity of symptoms. Many key processes in the inflammatory
      cascade have been targeted by cytokine and anticytokine therapies ranging from
      antigen presentation, T cell activation, overproduction of pro-inflammatory
      cytokines and migration of inflammatory cells to blockade of effector signals.
      TNF-alpha plays an important role in the induction of other cytokines as well as
      in the upregulation of adhesion molecules in chronic IBDs, Crohn's disease (CD)
      and ulcerative colitis. In fact, the most successful approaches so far in the
      treatment of IBD have been anti-TNF strategies. In contrast, the use of
      antiadhesion molecules strategies has been demonstrated to be ineffective in IBD.

PMID- 14661994
TI  - Advances in antiplatelet therapy.
AB  - Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality
      in the western world. These disorders share a common pathophysiology --
      atherosclerosis, which affects various arterial beds, leading to protean
      manifestations (coronary artery disease [CAD], stroke, peripheral arterial
      disease [PAD]). The platelet plays a pivotal role in the perpetuation and
      clinical expression of these disorders. The platelet, once believed to have a
      role confined to modulation of thrombosis and haemostasis, also plays an active
      role in vascular inflammation. Antiplatelet agents have become first-line therapy
      for CVD, and their unequivocal benefits are demonstrated in various basic and
      experimental models and supported by overwhelming evidence from clinical trials.
      Search is underway for more effective and safer antiplatelet therapy. Novel
      therapies are emerging to target the redundant pathways of platelet adhesion,
      activation and aggregation. Efforts are also ongoing to enhance implementation of
      existent therapy, target therapy selectively to high-risk patients and to those
      likely to respond (pharmacogenomics), and study the incremental benefits and
      safety of various antiplatelet combinations and their interaction with other
      medications in patients with CVD treated with polypharmacy.

PMID- 14661995
TI  - New lipid-lowering agents.
AB  - Lipid-lowering is established as a proven intervention to reduce atherosclerosis
      and its complications. This article summarises imminent developments in lipid
      lowering therapy, including new statins and cholesterol absorption inhibitors
      currently undergoing investigation for licensing. It also discusses other
      therapeutic targets such as squalene synthase, microsomal transfer protein (MTP),
      acyl-cholesterol acyl transferase (ACAT), cholesterol ester transfer protein
      (CETP), peroxosimal proliferator activating receptors (PPARs) and lipoprotein (a)
      (LP(a)), for which compounds have been developed and have at least reached trials
      in animal models. Lipid-lowering drugs are likely to prove a fast-developing area
      for novel treatments, as possible synergies exist between new and established
      compounds for the treatment of atherosclerosis.

PMID- 14661996
TI  - Emerging drugs in the management of hypertension.
AB  - Hypertension is a global health problem, affecting developing and developed
      countries alike. Most patients with hypertension are undiagnosed, and most
      diagnosed patients are either untreated or inadequately treated. Randomised
      controlled trial evidence suggests diuretic therapy for hypertension is as
      effective as newer drugs in reducing cardiovascular events. There is good
      evidence for the use of specific classes of drugs in hypertensive patients with a
      variety of associated clinical conditions, but for uncomplicated cases, the
      current emphasis in hypertension management is on blood pressure lowering rather
      than drug class. Individual patients vary in their responses to different drug
      classes, and optimal therapy for the individual is determined by trial and error.
      Pharmacogenomics may assist in tailoring therapy for individuals in the future.
      Emerging drugs include newer members of classes already established in clinical
      practice, for example, angiotensin II receptor antagonists, aldosterone receptor
      antagonists, calcium antagonists and centrally acting drugs; newer fixed-dose
      combination therapies; and more novel therapies, for example, endothelin (ET)
      receptor antagonists, activators of nitric oxide (NO)-sensitive guanylyl cyclase
      and vasopeptidase inhibitors.

PMID- 14661997
TI  - Emerging drugs for renal failure.
AB  - Renal failure involves a significant impairment of the essential functions of the
      kidney, which can be either acute with sudden and rapid onset (acute renal
      failure [ARF]) or chronic with gradual onset (chronic renal failure [CRF]). ARF,
      if detected early, may be halted or reversed, whereas CRF is generally
      irreversible. Without treatment or intervention, both forms of renal failure lead
      to end stage renal failure (ESRF) or end stage renal disease (ESRD), requiring
      renal replacement therapy (RRT) in the form of dialysis or renal transplantation
      for survival. However, provision of RRT requires expert teams working in
      specialised units, making therapy of patients with renal failure expensive;
      furthermore, RRT is complex, with its own complications. Although pharmacological
      interventions have shown promise in experimental models, these have not been as
      successful in the clinical setting (e.g., administration of atrial natriuretic
      peptide, low-dose dopamine). At present, drugs are administered during CRF to
      either reduce one of the many risk factors of CRF (e.g., angiotensin-converting
      enzyme inhibitors, statins) or to deal with the consequences of CRF (e.g.,
      erythropoietin, calcitriol). Recent evidence suggests that some of these
      interventions may provide further direct beneficial effects via reduction of
      renal inflammation. Although these interventions have greatly improved the
      prospects for patients suffering ESRF, the development of novel drugs and
      therapies with which to reduce the consequences of renal failure and ESRD remain
      topics of great interest. This article reviews the therapies available for the
      prevention and management of renal failure in adults and describes, in detail,
      emerging drugs and novel interventions that may soon become available for the
      treatment or prevention of ESRF.

PMID- 14661998
TI  - Emerging drugs in migraine treatment.
AB  - Ergot alkaloids have been the mainstay of acute migraine therapy for most of the
      20th century. They have been supplanted by sumatriptan-like drugs ('triptans'),
      which, while keeping some of the ergots mechanisms of action, show improved
      safety profiles due to their increased receptor selectivity. However, triptans
      are still far from being perfect drugs: they can constrict human coronary
      arteries at therapeutic doses and, therefore, are contra-indicated in the
      presence of cardiovascular disease. Another problem with these agents is
      recurrence of moderate-to-severe pain within 24 h of initial headache relief.
      While mechanism-driven drug design has led to the development of various novel,
      albeit still imperfect, acute antimigraine medications, only a few new
      prophylactic agents have been made available to migraine clinicians. The efficacy
      of most, if not all of them has been discovered serendipitously. This is probably
      due to the fact that, while the pathophysiology of a migraine attack is now
      reasonably understood, the mechanisms leading to an attack are still mostly
      unknown. This update analyses the profile of some antimigraine drugs in clinical
      trials, their mode of action and their potential advantages or drawbacks over
      already available agents.

PMID- 14661999
TI  - Medical treatment of epilepsy.
AB  - The licensing of new antiepileptic drugs (AEDs) has led to a marked increase in
      the pharmaceutical armamentarium available for the treatment of epilepsy since
      1990. The new drugs have now secured their place in the pharmacotherapy of
      epilepsy. The main reason for their success is their good general tolerability
      (especially with regard to cognitive function), the low rate of drug-drug
      interaction and the high anticonvulsant potency of some of the compounds. It is
      fortunate that many of the new AEDs have also proven effective in the treatment
      of generalised seizures, although they were originally developed for the
      treatment of focal seizures. However, the wide treatment choice has not solved
      the problems associated with the medical treatment of epilepsy. In monotherapy,
      none of the new AEDs have been shown to be superior in their potency to control
      seizures to older AEDs in comparative studies. Nonetheless, the greater choice of
      drugs allows treatment to be better tailored to the requirements of individual
      patients. Now there is a need to study patients whose seizures were not
      controlled by initial or alternative monotherapy to create an evidence-base for
      truly rational combination therapy in the future. Additional improvements in the
      medical treatment of epilepsy may come from AEDs currently in development, many
      of which use novel or unknown modes of action. So far, however, there is no
      evidence that any of these compounds will have radically different effects from
      the drugs currently available, or that they will have antiepileptic rather than
      purely anticonvulsant potential.

PMID- 14662000
TI  - Bisphosphonate therapy in the oncology setting.
AB  - Patients with metastatic cancer and bone involvement are at chronic risk of
      skeletal complications, including bone pain, fractures, spinal cord compression
      and hypercalcaemia of malignancy. Therapies targeting the primary malignancy are
      often unable to prevent skeletal complications, which often require orthopaedic
      surgery, radiation therapy and analgesics. Intravenous bisphosphonates can reduce
      the risk of skeletal complications and the requirement for palliative radiation
      therapy. Since its broad regulatory approval, zoledronic acid (ZOMETA, Novartis
      Pharma AG/Novartis Pharmaceuticals Corporation) 4 mg by 15-minute intravenous
      infusion has become widely used to treat bone metastases from all solid tumours
      and is becoming the standard of care for advanced breast cancer and multiple
      myeloma. Additionally, cancer treatment-induced bone loss is an emerging problem
      in clinical oncology, and bisphosphonates -- particularly intravenous
      bisphosphonates -- may provide benefits even before bone lesions develop. Further
      investigations of bisphosphonates in these and other indications are ongoing.

PMID- 14662001
TI  - Cancer vaccines entering Phase III clinical trials.
AB  - The last 10 years have seen a growth in the number of tumour antigens identified
      from immune responses raised in patients. The discovery that tumours can be
      recognised by the immune system stimulated a great deal of work characterising
      the molecular mechanisms underlying immune recognition. This in turn has led to
      an impressive array of immunological approaches to the generation of cancer
      vaccines; these range from molecularly defined T cell epitopes, antibody-based
      vaccines, cytokine therapies, immune modulators and DNA vaccines, to whole cell
      vaccines and, more recently, combinations of these methods. Many of these
      approaches have entered Phase I/II trials and have shown interesting clinical
      results. Moreover, they have extended our knowledge of the immune system and our
      understanding of the mechanisms required to design a successful cancer vaccine.
      This review outlines some of the approaches that have led to some of these
      vaccines entering Phase III clinical trials, discusses their modes of action and
      reports on their current status in trial.

PMID- 14662002
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors in late stage
      clinical trials.
AB  - The epidermal growth factor receptor (EGFR) is a cell membrane receptor that
      plays a key role in cancer development and progression. Ligand-activated EGFR
      dependent signalling is involved in cell proliferation, apoptosis, angiogenesis
      and metastatic spread. Targeting the EGFR, therefore, represents a promising
      molecular approach in cancer treatment. Several anti-EGFR agents are in clinical
      development. Three drugs are currently in Phase II and III development as single
      agents, or in combination with other anticancer modalities: IMC-225
      (cetuximab/Erbitux; ImClone), a chimaeric human-mouse monoclonal IgG(1) antibody,
      which blocks ligand binding and functional activation of the EGFR; OSI-774
      (erlotinib/Tarceva; Genentech/OSI/Roch) and ZD1839 (gefitinib/Iressa;
      AstraZeneca), two small molecule EGFR-selective inhibitors of tyrosine kinase
      enzymatic activity, which prevent EGFR autophosphorylation and activation. Iressa
      is the first EGFR-targeting agent to be registered as an anticancer drug in
      Japan, in Australia and in the US for the third-line treatment of chemoresistant
      non-small cell lung cancer (NSCLC) patients. This review will focus on the
      preclinical background and on the results from the first series of clinical
      trials with these drugs. Furthermore, continuing clinical trials and a series of
      open clinical issues for the development of optimal strategies of using EGFR
      targeting agents will be discussed.

PMID- 14662003
TI  - Emerging therapies for female sexual dysfunction.
AB  - Epidemiological studies in the US, the UK and Sweden indicate that approximately
      40% of women aged 18 - 59 have significant complaints about their sexual lives.
      The majority of complaints concern low sexual desire. Other common problems
      include difficulty reaching orgasm, insufficient lubrication and painful coitus.
      A vacuum erection device which increases blood flow to the clitoris has been
      approved by the US Food and Drug Administration. There are no pharmacological
      agents with approval for the treatment of female sexual dysfunction.
      Phosphodiesterase inhibitors and other drugs which cause genital vasocongestion
      in women appear to have minimal clinical efficacy. Although many of these agents
      increase the vasocongestive response to sexual stimulation, there is minimal
      correlation between subjective and objective measures of sexual arousal in women.
      Trials with androgens have clearly and convincingly demonstrated that
      supraphysiological doses of testosterone increase libido in postmenopausal women.
      The long-term safety of such doses is unclear. To date, no studies have shown
      lower doses of androgens to be beneficial. There have been minimal studies of
      drugs targeting the central nervous system to date. Bupropion may have a
      beneficial effect on orgasm attainment in women with hypoactive sexual desire
      disorder.

PMID- 14662004
TI  - Emerging drug treatments for cystic fibrosis.
AB  - Cystic fibrosis (CF) is one of the most common life-shortening inherited
      disorders. Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene
      disrupt the localisation and function of the cAMP-mediated chloride channel. Most
      of the morbidity and mortality arise from the lung disease which is characterised
      by excessive inflammation and chronic infection. Research into the mechanisms of
      wild-type and mutant CFTR biogenesis suggest that multiple drug targets can be
      identified. This review explores the current understanding of the nature of the
      different mutant CFTR forms and the potential for repair of the chloride channel
      defect. High-throughput screening, pharmacogenomics and proteomics bring recent
      technological advances to the field.

PMID- 14662005
TI  - Adenosine receptor agonists: from basic medicinal chemistry to clinical
      development.
AB  - Adenosine is a physiological nucleoside which acts as an autocoid and activates G
      protein-coupled membrane receptors, designated A(1), A(2A), A(2B) and A(3).
      Adenosine plays an important role in many (patho)physiological conditions in the
      CNS as well as in peripheral organs and tissues. Adenosine receptors are present
      on virtually every cell. However, receptor subtype distribution and densities
      vary greatly. Adenosine itself is used as a therapeutic agent for the treatment
      of supraventricular paroxysmal tachycardia and arrhythmias and as a
      vasodilatatory agent in cardiac imaging. During the past 20 years, a number of
      selective agonists for A(1), A(2A) and A(3) adenosine receptors have been
      developed, all of them structurally derived from adenosine. Several such
      compounds are currently undergoing clinical trials for the treatment of
      cardiovascular diseases (A(1)and A(2A)), pain (A(1)), wound healing (A(2A)),
      diabetic foot ulcers (A(2A)), colorectal cancer (A(3)) and rheumatoid arthritis
      (A(3)). Clinical evaluation of some A(1) and A(2A) adenosine receptor agonists
      has been discontinued. Major problems include side effects due to the wide
      distribution of adenosine receptors; low brain penetration, which is important
      for the targeting of CNS diseases; short half-lifes of compounds; or a lack of
      effects, in some cases perhaps due to receptor desensitisation or to low receptor
      density in the targeted tissue. Partial agonists, inhibitors of adenosine
      metabolism (adenosine kinase and deaminase inhibitors) or allosteric activators
      of adenosine receptors may be advantageous for certain indications, as they may
      exhibit fewer side effects.

PMID- 14662006
TI  - Metabolic Diseases Drug Discovery World Summit.
AB  - This year's Metabolic Diseases Drug Discovery World Summit, consisting of a
      gathering of mostly researchers from pharmaceutical and biotech industry, was
      held in picturesque San Diego. The diverse programme covered recent advances in
      drug discovery and development for the treatment of type II diabetes, metabolic
      syndrome and obesity. The ranges of topics included basic physiology, therapeutic
      target identification/validation, lead development/optimisation, profiling of
      development candidates and update on clinical trials. This report will attempt to
      highlight some of the important developments presented at this symposium.

PMID- 14662007
TI  - Lipid rafts: heterogeneity on the high seas.
AB  - Lipid rafts are membrane microdomains that are enriched in cholesterol and
      glycosphingolipids. They have been implicated in processes as diverse as signal
      transduction, endocytosis and cholesterol trafficking. Recent evidence suggests
      that this diversity of function is accompanied by a diversity in the composition
      of lipid rafts. The rafts in cells appear to be heterogeneous both in terms of
      their protein and their lipid content, and can be localized to different regions
      of the cell. This review summarizes the data supporting the concept of
      heterogeneity among lipid rafts and outlines the evidence for cross-talk between
      raft components. Based on differences in the ways in which proteins interact with
      rafts, the Induced-Fit Model of Raft Heterogeneity is proposed to explain the
      establishment and maintenance of heterogeneity within raft populations.

PMID- 14662008
TI  - Regulation of the enzymes of hepatic microsomal triacylglycerol lipolysis and re
      esterification by the glucocorticoid dexamethasone.
AB  - Hepatic VLDL (very-low-density lipoprotein) assembly is a complex process that is
      largely regulated by the provision of lipid for apolipoprotein B assembly.
      Intracellular stored TAG (triacylglycerol) undergoes an initial lipolysis
      followed by re-esterification of the lipolytic products to form TAG prior to
      their incorporation into a VLDL particle. TGH (TAG hydrolase) is a lipase that
      hydrolyses intracellular TAG within the hepatocyte. We have utilized both
      dexamethasone-injected mouse and primary hepatocyte models to address whether
      stimulation of TAG biosynthesis by the synthetic glucocorticoid, dexamethasone,
      altered hepatic lipolysis and re-esterification and the provision of stored TAG
      for lipoprotein secretion. Dexamethasone treatment resulted in decreased TGH
      expression, primarily due to a dexamethasone-induced decrease in TGH mRNA
      stability. The expression and activities of diacylglycerol acyltransferases 1 and
      2 were stimulated by dexamethasone. The combination of reduced intracellular TAG
      lipolysis and increased TAG biosynthesis contributed to the accumulation of TAG
      within the livers of dexamethasone-injected mice. The rate of hepatic TAG
      secretion in dexamethasonetreated mice was maintained at similar levels as in
      control mice. Our data demonstrate that stimulation of de novo TAG synthesis by
      dexamethasone increased the proportion of secreted TAG that was derived from de
      novo sources, while the utilization of stored TAG for secretion was reduced. The
      results show that, during markedly increased TAG synthesis, some TAGs are
      diverted from the cytosolic storage pool and are utilized directly for VLDL
      assembly within the endoplasmic reticulum lumen.

PMID- 14662009
TI  - Functional refolding of the Campylobacter jejuni MOMP (major outer membrane
      protein) porin by GroEL from the same species.
AB  - Functional and structural studies of outer membrane proteins from Gram-negative
      bacteria are frequently carried out using refolded proteins. Recombinant proteins
      are produced in Escherichia coli as inclusion bodies and then tediously refolded
      by dilution in buffered detergent solutions. In the present work, we obtained the
      refolding of MOMP (major outer membrane protein) from Campylobacter assisted by
      the molecular chaperone GroEL. Refolded MOMP recovered its native pore-forming
      activity when reconstituted in planar lipid bilayers. Both proteins were purified
      from the Campylobacter jejuni strain 85H. The purity of GroEL was assessed by
      silver staining and MS. Its native ultrastructure was observed by the use of
      transmission electron microscopy. Denaturation of MOMP was performed in urea at
      65 degrees C followed by dialysis against 100 mM acetic acid, and was assessed by
      CD analysis. MOMP refolding reached a maximum efficiency in the presence of GroEL
      (at a MOMP/GroEL molar ratio of 9:1) and ATP. Under these conditions, 95% of
      denatured MOMP was refolded after a 15 min incubation. This approach represents
      an alternative method in studies of membrane protein refolding.

PMID- 14662010
TI  - Introduction of article-processing charges (APCs) for articles accepted for
      publication in the Journal of Translational Medicine.

PMID- 14662011
TI  - Differential effects of fenofibrate versus atorvastatin on the concentrations of
      E-selectin and vascular cellular adhesion molecule-1 in patients with type 2
      diabetes mellitus and mixed hyperlipoproteinemia: a randomized cross-over trial.
AB  - BACKGROUND: Diabetic dyslipoproteinemia is characterized by hypertriglyceridemia,
      low HDL-cholesterol and often elevated LDL-cholesterol and is a strong risk
      factor for atherosclerosis. Adhesion molecule levels are elevated both in
      hyperlipoproteinemia and diabetes mellitus. It is unclear whether fibrate or
      statin therapy has more beneficial effects on adhesion molecule concentrations.
      METHODS: Atorvastatin (10 mg/d) was compared to fenofibrate (200 mg/d) each for 6
      weeks separated by a 6 week washout period in 11 patients (6 male, 5 female; 61.8
      +/- 8.2 years; body mass index 29.8 +/- 3.1 kg/m2) with type 2 diabetes mellitus
      (HbA1c 7.3 +/- 1.1%) and mixed hyperlipoproteinemia using a randomized, cross
      over design. Fasting blood glucose, HbA1c, lipid parameters, E-selectin, ICAM-1,
      VCAM-1, and fibrinogen concentrations were determined before and after each drug.
      RESULTS: Glucose and HbA1c concentrations remained unchanged during the whole
      study period. LDL cholesterol was reduced during atorvastatin therapy,
      triglycerides were lowered more effectively with fenofibrate. Comparison of pre-
      and postreatment concentrations of E-selectin showed a reduction during
      atorvastatin (-7%, p = 0.11) and fenofibrate (-10%, p < 0.05) therapy.
      Atorvastatin treatment reduced VCAM-1 levels by 4% (p < 0.05), while VCAM-1
      concentrations remained unchanged (+1%, ns) during fenofibate therapy. However,
      direct comparisons of post-treatment levels during both forms of therapy were not
      of statistical significance. ICAM-1 levels were not influenced by either form of
      therapy. CONCLUSIONS: In addition to the different beneficial effects on lipid
      metabolism, both drugs appear to lower adhesion molecule plasma concentrations in
      a different manner in patients with type 2 diabetes and mixed
      hyperlipoproteinemia. Our observations should be confirmed in a larger cohort of
      such patients.

PMID- 14662012
TI  - A randomised controlled trial to assess the efficacy of Laparoscopic Uterosacral
      Nerve Ablation (LUNA) in the treatment of chronic pelvic pain: The trial protocol
      [ISRCTN41196151].
AB  - BACKGROUND: Chronic pelvic pain is a common condition with a major impact on
      health-related quality of life, work productivity and health care utilisation.
      The cause of the pain is not always obvious as no pathology is seen in 40-60% of
      the cases. In the absence of pathology there is no established treatment. The Lee
      Frankenhauser sensory nerve plexuses and parasympathetic ganglia in the
      uterosacral ligaments carry pain from the uterus, cervix and other pelvic
      structures. Interruption of these nerve trunks by laparoscopic uterosacral nerve
      ablation (LUNA) may alleviate pain. However, the balance of benefits and risks of
      this intervention have not been reliably assessed. LUNA has, nevertheless, been
      introduced into practice, although there remains controversy regarding
      indications for LUNA. Hence, there is an urgent need for a randomised controlled
      trial to confirm, or refute, any worthwhile effectiveness. The principal
      hypothesis is that, in women with chronic pelvic pain in whom diagnostic
      laparoscopy reveals either no pathology or mild endometriosis (AFS score </= 5)
      LUNA alleviates pain and improves life quality at 12 months. METHODS/DESIGN: The
      principal objective is to test the hypothesis that in women with chronic pelvic
      pain in whom diagnostic laparoscopy reveals either no pathology or mild
      endometriosis (AFS score </= 5) LUNA alleviates pain and improves life quality at
      12 months. A multi-centre, prospective, randomised-controlled-trial will be
      carried out with blind assessment of outcomes in eligible consenting patients
      randomised at diagnostic laparoscopy to LUNA (experimental group) or to no pelvic
      denervation (control group). Postal questionnaires including visual analogue
      scale for pain (primary outcome), an index of sexual satisfaction and the EuroQoL
      5D-EQ instrument (secondary outcomes) will be administered at 3, 6 and 12 months.
      The primary assessment of the effectiveness of LUNA will be from comparison of
      outcomes at the one-year follow-up, although the medium-term and longer-term
      risks and benefits of LUNA will also be evaluated.The sample size for this trial
      has been estimated as 420 patients in total using the hypothesis that LUNA will
      alleviate pain symptoms (i.e. reduce pain scores on a VAS) more than no
      intervention at one-year following diagnostic laparoscopy and taking into
      consideration 20% loss to follow-up. The intention to treat analysis to address
      the principal research questions will be conducted using the one-year follow-up
      data.

PMID- 14662013
TI  - Risk factors for antibiotic resistance in Campylobacter spp. isolated from raw
      poultry meat in Switzerland.
AB  - BACKGROUND: The world-wide increase of foodborne infections with antibiotic
      resistant pathogens is of growing concern and is designated by the World Health
      Organization as an emerging public health problem. Thermophilic Campylobacter
      have been recognised as a major cause of foodborne bacterial gastrointestinal
      human infections in Switzerland and in many other countries throughout the world.
      Poultry meat is the most common source for foodborne cases caused by
      Campylobacter. Because all classes of antibiotics recommended for treatment of
      human campylobacteriosis are also used in veterinary medicine, in view of food
      safety, the resistance status of Campylobacter isolated from poultry meat is of
      special interest. METHODS: Raw poultry meat samples were collected throughout
      Switzerland and Liechtenstein at retail level and examined for Campylobacter spp.
      One strain from each Campylobacter-positive sample was selected for
      susceptibility testing with the disc diffusion and the E-test method. Risk
      factors associated with resistance to the tested antibiotics were analysed by
      multiple logistic regression. RESULTS: In total, 91 Campylobacter spp. strains
      were isolated from 415 raw poultry meat samples. Fifty-one strains (59%) were
      sensitive to all tested antibiotics. Nineteen strains (22%) were resistant to a
      single, nine strains to two antibiotics, and eight strains showed at least three
      antibiotic resistances. Resistance was observed most frequently to ciprofloxacin
      (28.7%), tetracycline (12.6%), sulphonamide (11.8%), and ampicillin (10.3%). One
      multiple resistant strain exhibited resistance to five antibiotics including
      ciprofloxacin, tetracycline, and erythromycin. These are the most important
      antibiotics for treatment of human campylobacteriosis. A significant risk factor
      associated with multiple resistance in Campylobacter was foreign meat production
      compared to Swiss meat production (odds ratio = 5.7). CONCLUSION: Compared to the
      situation in other countries, the data of this study show a favourable resistance
      situation for Campylobacter strains isolated from raw poultry meat produced in
      Switzerland. Nevertheless, the prevalence of 19% ciprofloxacin resistant strains
      is of concern and has to be monitored. "Foreign production vs. Swiss production"
      was a significant risk factor for multiple resistance in the logistic regression
      model. Therefore, an adequate resistance-monitoring programme should include meat
      produced in Switzerland as well as imported meat samples.

PMID- 14662015
TI  - Tumor hypoxia: a target for selective cancer therapy.
AB  - Tumor hypoxia has been considered to be a potential therapeutic problem because
      it renders solid tumors more resistant to sparsely ionizing radiation (IR) and
      chemotherapeutic drugs. Moreover, recent laboratory and clinical data have shown
      that tumor hypoxia is also associated with a more malignant phenotype and poor
      survival in patients suffering from various solid tumors. Therefore, selective
      targeting of hypoxic tumor cells has been explored, and since severe hypoxia
      (pO(2) < 0.33%, 2.5 mmHg) does not occur in normal tissue, tumor hypoxia could be
      exploited for therapeutic advantage. However, the following three characteristics
      of hypoxic tumor regions present obstacles in targeting hypoxic cells. First, it
      is difficult to deliver a sufficient amount of drug to a region that is remote
      from blood vessels. Second, one must specifically target hypoxic tumor cells
      while sparing normal well-oxygenated tissue from damage. Finally, the severely
      hypoxic tumor cells to be attacked have often stopped dividing. Therefore, high
      delivery efficiency, high specificity and selective cytotoxicity are all
      necessary to target and combat hypoxic tumor cells. The current review describes
      progress on the biological aspects of tumor hypoxia and provides a compilation of
      the recent molecular approaches used to target hypoxic tumors. These approaches
      include our work with a unique hypoxia-targeting protein drug, TOP3, with which
      we have sought to address the above three difficulties.

PMID- 14662016
TI  - The role of Gab family scaffolding adapter proteins in the signal transduction of
      cytokine and growth factor receptors.
AB  - The Grb2-associated binder (Gab) family adapter proteins are scaffolding adapter
      molecules that display sequence similarity with Drosophila DOS (daughter of
      sevenless), which is a substrate for the protein tyrosine phosphatase Corkscrew.
      Gab proteins contain a pleckstrin homology (PH) domain and binding sites for SH2
      and SH3 domains. A number of studies in multiple systems have implicated Gab in
      signaling via many different types of receptors, such as growth factor, cytokine,
      and antigen receptors, and via oncoproteins. Recent studies of Gab1 and Gab2
      knockout mice have clearly indicated an important role for Gabs in vivo. Gab1
      deficient mice die as embryos with multiple defects in placental, heart, skin,
      and muscle development. Gab2-deficient mice are viable, but have a defect in the
      mast cell lineages and in allergic reactions. Given the apparently central role
      played by Gab signaling via many receptors, delineating the precise mechanism(s)
      of Gab-mediated signaling is critical to understanding how cytokines, growth
      factors, and oncoproteins mediate a variety of biological activities: cell
      growth, differentiation, survival and malignant transformation.

PMID- 14662017
TI  - Hepatoma-derived growth factor induces tumorigenesis in vivo through both direct
      angiogenic activity and induction of vascular endothelial growth factor.
AB  - Hepatoma-derived growth factor (HDGF) is highly expressed in tumor cells, and
      stimulates their proliferation. In the present study, we investigated the role of
      HDGF in tumorigenesis and elucidated the mechanism of action. Stable
      transfectants of NIH3T3 cells overexpressing HDGF did not show significant
      anchorage-independent growth in soft agar assay. However, these stable
      transfectants overexpressing HDGF generated sarcomatous tumors in nude mice.
      These tumors were red-colored macroscopically, and histologically showed a rich
      vascularity. Immunohistochemical analysis using CD31 antibody showed new vessel
      formation. Recombinant HDGF stimulated proliferation of human umbilical vein
      endothelial cells in a dose-dependent manner, and stimulated tubule formation.
      Furthermore, vascular endothelial growth factor (VEGF) was detected
      immunohistochemically in the tumor tissues. Transient expression of HDGF induced
      both VEGF gene and protein expression as demonstrated by a reporter assay using
      VEGF gene promoter. The administration of anti-VEGF neutralizing antibody
      significantly suppressed, but did not block, the tumor growth of HDGF
      overexpressing cells in nude mice. Thus, these findings suggested that HDGF
      induced tumor formation in vivo involves induction of VEGF as well as direct
      angiogenic activity.

PMID- 14662018
TI  - Lack of effect of human c-Ha-ras proto-oncogene overexpression on prostate
      carcinogenesis in probasin/SV40 T antigen transgenic rats.
AB  - We have previously reported that transgenic (Tg) rats bearing the SV40 T antigen
      under probasin promoter control (PB/SV40T) develop prostate carcinomas at 100%
      incidence, showing their prostate carcinoma growth to be completely androgen
      dependent. Transgenic rats carrying three copies of the human c-Ha-ras proto
      oncogene (Hras128) are also highly susceptible to carcinogen induction of
      multiple mammary carcinomas, in this case estrogen-independent, since ovariectomy
      does not affect mammary tumor formation. A relationship between ras/mitogen
      activated protein kinase signaling and androgen responsiveness of prostate cancer
      cells has been reported. Therefore it is of interest to investigate whether
      expression of human c-Ha-ras affects the androgen-dependence of prostate
      carcinomas developing in the PB/SV40T Tg rat. For this purpose, we established
      double transgenic (rasTag) rats bearing both PB/SV40T and Hras128. In prostate
      tissues of the rasTag rats, expression of both human c-Ha-ras and SV40T was
      confirmed, but the prostate tumor incidence and growth were not significantly
      affected. Castration at 15 weeks of age induced complete tumor involution in the
      rasTag rats. These results indicate that the human c-Ha-ras proto-oncogene
      product does not influence the androgen-dependence of prostate carcinogenesis due
      to the probasin-mediated SV40 T antigen, despite the estrogen-independence of
      mammary carcinogenesis in Hras128 rats.

PMID- 14662019
TI  - beta-Catenin mutations and nuclear accumulation during progression of rat stomach
      adenocarcinomas.
AB  - Aberrant Wnt/beta-catenin signaling caused by mutations in exon 3 of the beta
      catenin gene has been identified in a number of human malignancies, including
      stomach cancer. However, studies of mutation frequency have yielded conflicting
      results, and timing during progression remains largely unknown. In this study, we
      utilized an animal model to address this question. A total of 20 ACI male rats
      were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking
      water and 22 induced differentiated adenocarcinomas were histopathologically and
      immunohistochemically evaluated for beta-catenin localization. Fourteen tumors
      (63.6%) that showed homogeneous low-grade morphology, preserving cell polarity,
      were found to harbor beta-catenin protein on the cell membranes (M). Eight tumors
      exhibited regions of high-grade morphology among areas with low-grade morphology,
      and they were characterized by denser cell growth and loss of cell polarity.
      Among these 8 tumors, 4 (18.2%) showed cytoplasmic localization (C) of beta
      catenin in small regions. The remaining 4 tumors (18.2%) contained more
      dysplastic regions that displayed nuclear (N) beta-catenin staining. Analysis of
      DNA obtained by microdissection demonstrated that all of 4 regions with C
      staining and 20 with M staining, as well as 17 samples of surrounding normal
      mucosa (S) had wild-type beta-catenin. In contrast, all of 3 regions with N
      staining featured mutations (3 of 3 = 100%; N vs. C, P < 0.05; N vs. M and N vs.
      S, P < 0.001, Fisher's exact test) in exon 3, at glycine 34, threonine 41, and
      serine 45, which affected phosphorylation sites. In conclusion, beta-catenin
      mutations appear to be associated with the late progression stage of
      adenocarcinoma development in rat stomach carcinogenesis, in contrast to the case
      of colorectal cancers, in which mutations appear to occur in the early stages.

PMID- 14662020
TI  - Significance of overexpression of metallothionein in mouse urinary bladder focal
      lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine.
AB  - Metallothionein (MT) is expressed in various types of human tumors, including
      transitional cell carcinomas of the urinary bladder, but its biological
      significance remains unclear. In the present study, the role of MT in urinary
      bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
      treatment was investigated using C57BL/6 mice. One hundred 5-week-old male
      C57BL/6 mice were divided into two groups, which were given drinking water with
      or without 0.05% BBN throughout the experimental period. Subgroups of ten animals
      from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary
      bladder samples were examined immunohistochemically for MT, proliferating cell
      nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal
      looking mucosa, but decreased with progression from precancerous lesions to
      invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions
      could be divided into MT-positive and negative. There was a tendency for greater
      MT expression in PCNA-positive lesions, while apoptosis was rather associated
      with MT-negativity. These data suggest that the overexpression of MT may play a
      role in mouse urinary bladder carcinogenesis.

PMID- 14662021
TI  - Expression of pericyte, mesangium and muscle markers in malignant rhabdoid tumor
      cell lines: differentiation-induction using 5-azacytidine.
AB  - Malignant rhabdoid tumor (MRT) has been considered to have multiphenotypic
      diversity characteristics. Some MRTs exhibit a neural phenotype. However, it is
      still unclear whether MRT cells can display a skeletal muscle, smooth muscle or
      smooth muscle-like cell phenotype, like those of pericytes and mesangial cells.
      To determine if MRTs exhibit skeletal muscle cell or smooth muscle-like cell
      phenotypes, six MRT cell lines (TM87-16, STM91-01, TTC549, TTC642, YAM-RTK1 and
      TTC1240) were examined for markers of skeletal muscle (MyoD, myogenin, myf-5, myf
      6, acetylcholine receptor-alpha, -beta and -gamma), smooth muscle (alpha-smooth
      muscle actin, SM-1 and SM22), and smooth muscle-like cells, such as pericytes
      (angiopoietin-1 and -2) and mesangial cells (megsin), using conventional RT-PCR,
      semi-quantitative PCR, western blotting and immunocytochemistry before and after
      differentiation-induction with 5-azacytidine. alpha-Smooth muscle actin and SM22
      were detected in all six MRT cell lines, while MyoD and myf-5, crucial markers
      for skeletal myogenic determination, were not. The TM87-16 cell line expressed SM
      1 and angiopoietin-1. TTC1240 also expressed angiopoietin-1. Interestingly, STM91
      01 expressed megsin, a novel marker for mesangial cells, in addition to
      angiopoietin-1. Our results indicated that some MRTs exhibited smooth muscle
      and/or smooth muscle-like cell phenotypes and some renal MRTs might be of
      mesangial origin. Recently, smooth muscle and also smooth muscle-like cells have
      been considered to be of neuroectodermal origin. MRT can thus considered to
      belong to the category of primitive neuroectodermal tumors (PNETs) in the broad
      sense.

PMID- 14662022
TI  - Upregulation of FLIP(S) by Akt, a possible inhibition mechanism of TRAIL-induced
      apoptosis in human gastric cancers.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent
      inducer of apoptosis in some, but not all cancer cells. To assess the regulation
      of TRAIL-resistance in the human gastric cancer cells, we examined TRAIL
      sensitivity, TRAIL receptor expression, and intracellular signaling events
      induced by TRAIL. All the gastric cancer cell lines tested were susceptible to
      TRAIL to some extent, except for SNU-216 cell line, which was completely
      resistant. TRAIL receptor expression was not related to the TRAIL-sensitivity. Of
      the cell lines tested, SNU-216 showed the highest level of constitutively active
      Akt and the short form of FLICE inhibitory protein (FLIP(S)). Treatment with the
      phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or with the protein
      synthesis inhibitor cycloheximide induced a suppression of constitutive Akt
      activation in SNU-216 cells and a concomitant decrease in the expression of
      FLIP(S). The reduction of Akt activity by LY294002 affected the transcriptional
      level of FLIP(S), but not the mRNA stability. As a result, LY294002 or
      cycloheximide significantly enhanced TRAIL-induced apoptosis. Moreover, the
      overexpression of constitutively active Akt in the TRAIL-sensitive cell line, SNU
      668, rendered the cell line resistant to TRAIL. In addition, infection of the
      same cell line with retrovirus expressing FLIP(S) completely inhibited TRAIL
      induced apoptosis by blocking the activation of caspase-8. Therefore, our results
      suggest that Akt activity promotes human gastric cancer cell survival against
      TRAIL-induced apoptosis via upregulation of FLIP(S), and that the cytotoxic
      effect of TRAIL can be enhanced by modulating the Akt/FLIP(S) pathway in human
      gastric cancers.

PMID- 14662023
TI  - Identification of candidate predictive markers of anticancer drug sensitivity
      using a panel of human cancer cell lines.
AB  - We previously investigated the correlations between the expression of 9216 genes
      and various chemosensitivities in a panel of 39 human cancer cell lines(1)) and
      found that the expression levels of AKR1B1 and CTSH were correlated with
      sensitivity and resistance to multiple drugs, respectively. To validate these
      correlations, we investigated the expression of these two genes and the
      chemosensitivities in 12 additional gastric cancer cell lines. The expression of
      AKR1B1 in the additional cell lines exhibited significant correlations with
      sensitivities to 8 of the 23 drugs examined, while that of CTSH displayed a
      significant negative correlation with only one (MS-247) of the 27 drugs examined.
      Their expressions were weakly correlated with sensitivity and resistance,
      respectively, to the remainder of the drugs. Moreover, when the 12 cell lines
      were divided into high-expressing and low-expressing groups, a comparison of
      these groups using Mann-Whitney's U test revealed that high expression levels of
      AKR1B1 and CTSH were related to sensitivity to 21 of the drugs and resistance to
      8 of the drugs, respectively. The present results suggest that AKR1B1 and CTSH
      may be good markers for prediction of sensitivity to certain drugs and that our
      panel of 39 cell lines has the potential to identify candidate predictive marker
      genes.

PMID- 14662024
TI  - Serum alanine aminotransferase levels and survival after hepatectomy in patients
      with hepatocellular carcinoma and hepatitis C virus-associated liver cirrhosis.
AB  - We examined whether sustained alleviation of inflammation as monitored by serum
      alanine aminotransferase (ALT) levels was associated with longer survival in
      hepatectomized hepatocellular carcinoma (HCC) patients with hepatitis C virus
      associated liver cirrhosis (HCV-LC). Thirty-four hepatectomized patients with HCV
      LC and HCC as a single nodule, and for whom more than 5 years had elapsed after
      the hepatectomy, were studied. They had no histologic evidence of portal or
      hepatic vein invasion. They were subdivided into two groups according to their
      serum ALT levels in the 2 years after hepatectomy: the low ALT group comprised 13
      patients whose serum ALT levels showed a sustained low level below 80 IU, and the
      high ALT group comprised 21 patients whose serum ALT levels showed several peaks
      or plateaus above 80 IU. The patients had been followed-up prospectively with
      frequent ultrasonography and magnetic resonance imaging or computed tomography
      for recurrence for > 5 years. The survival period, non-recurrence interval and
      number of recurrences were observed. Recurrences were treated with transcatheter
      chemoembolization in all cases. The cumulative survival rate in the low ALT group
      was significantly better than that in the high ALT group (P < 0.05). The 5-year
      survival in the low ALT group was as high as 92.3% (12 of 13) compared with 33.3%
      (7 of 21) in the high ALT group (P < 0.05). The cumulative non-recurrence rate in
      the low ALT group was also significantly better than that in the high ALT group
      (P < 0.01). The survival period correlated well with the interval until the first
      recurrence (r = 0.545, P = 0.006). There was a tendency for the number of
      recurrences in the low ALT group (1.5 +/- 0.4, mean +/- SE) to be fewer than that
      in the high ALT group (2.2 +/- 0.4), although this was not significant. Sustained
      alleviation of inflammation, as indicated by low ALT levels, provides a survival
      advantage mainly due to the longer non-recurrence interval, and possibly because
      of fewer recurrences, in hepatectomized HCC patients with HCV-LC.

PMID- 14662025
TI  - Generation of mature dendritic cells fully capable of T helper type 1
      polarization using OK-432 combined with prostaglandin E(2).
AB  - Dendritic cell (DC) administration appears to be a very promising approach for
      the immunotherapy of cancer. The results of clinical studies have suggested that
      the nature and the magnitude of antitumor immune responses are critically
      affected by DC functions, including production of T helper type 1 (Th1)-inducing
      cytokines, activation of T cell subsets and natural killer (NK) cells, and
      migration from peripheral tissues to the T cell area of the draining lymph nodes.
      Administration of immature DCs could fail to fully stimulate antigen-specific
      immune responses and might induce tolerance under some conditions. In this study,
      we developed a method to obtain fully mature DCs, and we compared in detail the
      DCs thus obtained with those obtained using a maturation stimulus termed monocyte
      derived medium (MCM)-mimic, which is a mixture of recombinant cytokines and
      prostaglandin E(2) (PGE(2)) mimicking the components of monocyte-conditioned
      medium. Using DCs derived from monocytes of advanced cancer patients in this
      study, we found that DCs stimulated with OK-432 alone showed phenotypes similar
      to those of mature DCs induced using MCM-mimic, though with better secretion of
      IL-6 and IL-12. However, these DCs were found to have poor migratory capacity
      associated with the marginal expression of CCR7. When OK-432 was combined with
      PGE(2), the CCR7 expression and migratory capacity of DCs were significantly
      improved without impairing other immuno-stimulatory functions. These results
      suggest that stimulation with the combination of OK-432 and PGE(2) could be
      applicable as an alternative to MCM-mimic in clinical trials which require fully
      matured DCs to induce Th1-type immune responses against tumor cells even in
      patients with advanced cancer.

PMID- 14662026
TI  - Leptomycin B enhances CDDP-sensitivity via nuclear accumulation of p53 protein in
      HPV-positive cells.
AB  - Cervical cancer, which commonly contains a wild-type p53 gene, is highly
      correlated with human papilloma virus (HPV) infection. Because the oncoprotein
      E6, derived from HPV, inhibits the function of p53 protein, the inhibition of
      apoptosis via the p53 pathway by HPV may be related to cisplatin (CDDP)
      sensitivity in cervical cancer. We conducted the present study to determine
      whether and how HPV is related to CDDP-sensitivity in HPV-positive cervical
      cancer cells. We used cervical carcinoma cell lines HeLa with integrated HPV 18
      and SiHa with integrated HPV 16. An HPV-negative cell line, Yumoto, with wild
      type p53 gene was used as a control. Leptomycin B (LMB) enhanced sensitivity to
      CDDP and CDDP-induced apoptosis in HeLa and SiHa cells, but not in Yumoto cells.
      After exposure to LMB or CDDP alone, we observed weak p53 staining in HeLa, SiHa
      and Yumoto cells. Nuclear p53 staining was significantly increased by combined
      treatment with CDDP and LMB in HeLa and SiHa cells, but not in Yumoto cells. The
      expression of p53 and Bax protein increased with exposure to CDDP and was
      enhanced by LMB in HeLa and SiHa cells. The present study demonstrated that LMB
      enhanced CDDP-sensitivity via nuclear accumulation of p53 protein in HPV-positive
      cells.

PMID- 14662027
TI  - Hematological aspects of a novel 9-aminoanthracycline, amrubicin.
AB  - Our previous study showed that the myelosuppression induced by a single-bolus
      intravenous injection of amrubicin into mice was more severe, even at half the
      maximum tolerated dose (MTD), than that induced by adriamycin (ADR) at the MTD,
      but that the recovery was more rapid than that after ADR. The present study shows
      that the administration of amrubicin significantly decreased the number of colony
      forming units of granulocytes and monocytes (CFU-GM) from day 1, but that the CFU
      GM numbers recovered by day 3. In contrast, the administration of ADR induced a
      continuous decrease in the numbers of CFU-GM until day 10. The early
      myelosuppression and rapid recovery of white blood cells (WBC) induced by
      amrubicin may depend upon the early decrease in the number of CFU-GM and the
      rapid recovery of CFU-GM. These data suggest that the toxic effects on the
      peripheral blood and bone marrow induced by amrubicin are more reversible and
      more controllable than those induced by ADR.

PMID- 14662028
TI  - Extragonadal germ cell tumors in Japan.
AB  - Extragonadal germ cell tumors (EGCT) represent only 2-5% of adult germ cell
      malignancies. Some publications from Asia have reported inferior treatment
      outcomes compared to data from an international study group. To ascertain whether
      this is generally the case, here we analyze treatment outcomes for 30 Japanese
      patients with EGCT. The medical records of 30 patients (25 nonseminomas and 4
      pure seminomas) treated from 1992 to 2002 were reviewed retrospectively. All
      patients with seminoma achieved long survival except one who died of chemotherapy
      related sepsis. Ten and 11 patients with EGCT presented with mediastinal and
      retroperitoneal primary sites, respectively. The 5-year overall survival (OS) and
      progression-free survival (PFS) for nonseminoma was 71% and 42%, respectively.
      The 5-year OS and PFS was 60% and 44%, respectively, for 10 patients with
      mediastinal nonseminoma, and 91% and 48%, respectively, for patients with
      retroperitoneal nonseminoma. Tumor marker values on day 7 were available for 19
      patients. Among the 19 patients in whom AFP or beta-HCG were measured on day 7,
      the values had declined in 12 patients and were transiently elevated in 7
      patients compared to pretreatment values. The transient elevations of tumor
      markers were significantly associated with poor OS (P = 0.02) and PFS (P =
      0.008). The treatment outcome of Japanese patients with EGCT seemed to be
      comparable to that reported from international studies, suggesting no difference
      between ethnic groups. Transient tumor marker elevations on day 7 predict poor
      survival in EGCT patients and may be a useful parameter for identifying patients
      requiring more aggressive treatment.

PMID- 14662029
TI  - LY900003 (Affinitac), an antisense inhibitor of protein kinase C-alpha, in non
      small-cell lung cancer.

PMID- 14662030
TI  - Pemetrexed (Alimta): a novel antifolate in the treatment of malignant pleural
      mesothelioma.

PMID- 14662031
TI  - Results of recent Japanese clinical trials in lung cancer.
AB  - Lung cancer is one of the most common cancers and its associated mortality
      continues to rise in Japan. The lung cancer cure rate is still very low. To
      improve the survival of patients with lung cancer, well-designed and well
      conducted clinical trials are essential. Several Japanese study groups have been
      conducting clinical trials for lung cancer. However, most randomized phase III
      studies were conducted by the Japan Clinical Oncology Group (JCOG), the West
      Japan Thoracic Oncology Group, and pharmaceutical companies supporting
      temporarily organized groups. In the past decade, the quality of Japanese
      clinical studies has improved tremendously. The results of JCOG9511 have recently
      been reported; and demonstrated that treatment with irinotecan/cisplatin
      significantly improved patient survival in extensive-stage small-cell lung cancer
      over standard etoposide/cisplatin, with less myelosuppression. A randomized phase
      II study using gefitinib (ZD1839; Iressa) for non-small-cell lung cancer was also
      recently reported and showed a high response rate against platinum-refractory
      lung cancer, especially in adenocarcinoma and in females. A 4-arm multicenter,
      randomized cooperative phase III study for advanced non-small-cell lung cancer is
      currently underway.

PMID- 14662032
TI  - The value of platinum compounds in non-small-cell lung cancer.
AB  - The value of platinum compounds has come into question with the advent of newer
      chemotherapy agents in the management of patients with advanced non-small-cell
      lung cancer. These newer agents, which include the taxanes, topoisomerase I
      inhibitors, gemcitabine, and vinorelbine, appear to have higher single-agent
      response rates and more favorable toxicity profiles when compared to the platinum
      compounds. However, the toxicity of the platinum compounds is now minimized with
      the advent of more effective antiemetics. In addition, phase III clinical trials
      have demonstrated that the strategy of cisplatin dose intensity and prolonged
      duration of therapy with platinum compounds does not improve overall survival;
      therefore, moderate doses of cisplatin and a shorter duration of therapy can be
      given to further decrease toxicity. Furthermore, while phase II trials utilizing
      nonplatinum-based combination chemotherapy appear to demonstrate superior
      response rates and survival in comparison to platinum-based doublets, results of
      phase III trials have demonstrated no improvement in survival. Platinum
      combination chemotherapy remains the standard approach for stage IV non-small
      cell lung cancer. More substantial advances will likely be made with novel
      molecular targeted therapy, such as the epidermal growth factor receptor
      inhibitors, which demonstrate synergy with the platinum compounds.

PMID- 14662033
TI  - Temozolomide in non-small-cell lung cancer: preliminary results of a phase II
      trial in previously treated patients.
AB  - Virtually all patients with advanced non-small-cell lung cancer (NSCLC) relapse.
      Docetaxel has an established, Food and Drug Administration-approved role as
      salvage therapy in previously treated, platinum-exposed patients. However, the
      response rate in phase III studies is < 15%, and median survival is only 6-8
      months. Temozolomide, a novel triazene derivative with activity in melanoma and
      anaplastic astrocytoma, has demonstrated activity in C26 adenocarcinoma, Lewis
      lung cancer, and in phase I studies. A phase II trial was mounted using a unique
      schedule of oral temozolomide 75 mg/m2 daily for 6 weeks every 8-10 weeks, in
      patients with previously treated, advanced, incurable NSCLC. Eligibility
      stipulated an Eastern Cooperative Oncology Group performance status (PS) of 0-2,
      adequate end organ function, up to 1 prior chemotherapy for advanced (relapsed or
      metastatic) disease, and up to 1 prior regimen in the context of
      radiosensitization, adjuvant therapy, or induction. From March 2000 through
      January 2002, 47 patients (24 male, 23 female) were enrolled. The median age was
      67 years. Sixteen patients had a PS of 2, 22 had a PS of 1, and 9 had a PS of 0.
      It was too early to evaluate 9 patients. Toxicity, with the exception of mild
      nausea and thrombocytopenia, was negligible. Three patients had a delayed
      recovery of platelets prompting discontinuation of treatment. Of the 38 evaluable
      patients, 1 patient had a complete response, 2 patients had a partial response,
      12 had stable disease, and 19 had disease progression. Four patients were not
      evaluable. Six patients died within 30 days of taking temozolomide; 5 of these
      deaths were not related to treatment upon review by an independent data safety
      monitoring committee. Temozolomide, using a unique 6-week continuous schedule,
      has demonstrated activity in the salvage therapy of advanced NSCLC. Toxicity is
      modest, and accrual to this study continues.

PMID- 14662034
TI  - Update on results of multifield conformal radiation therapy of non-small-cell
      lung cancer using multileaf collimated beams.
AB  - We evaluated the treatment outcome for 5-field 3-dimensional conformal radiation
      therapy (3D-CRT) in 46 consecutive patients with unresectable, nonmetastatic non
      small-cell lung cancer treated from 1993-2001. Four percent of the patients had
      stage I tumors, 6% had stage II, 44% had stage IIIA, and 46% had stage IIIB
      tumors. The median radiation therapy (RT) dose to the gross tumor volume with a
      median of 467.5 cc (range, 75.0-3073.0 cc) was 6120 cGy (range, 3000-6840 cGy).
      Thirty-one of 46 patients (67.4%) received combined chemoradiotherapy. Mean
      follow-up was 13.2 months (range, 3-159 months). Survival for stage III patients
      was 48.7% +/-9.1% at 1 year and 25.0% +/-8.4% at 2 years, with a median survival
      of 12.0 months+/-4.4 months. The local control rate for stage III patients was
      66.8%+/- 9.4% at 1 year and 28.5%+/- 10.4% at 2 years. Patients who received
      chemotherapy had better survival (P = 0.0533) and local control (P = 0.0984)
      compared with patients receiving RT alone. Esophageal toxicity >or= grade 3 was
      significantly greater in combined chemoradiotherapy patients (29% early, 13%
      late) compared to the patients receiving RT alone (0% early and late). Pulmonary
      toxicity (early and late) was limited to grades 1/2 in 24% of patients and early
      grade 3 in 2% of patients. Chemotherapy appears to improve survival and local
      control when added to 3D-CRT in this series. The addition of concurrent
      chemotherapy to RT significantly increased esophageal toxicity (within acceptable
      levels) and did not effect pulmonary toxicity in this series.

PMID- 14662035
TI  - Phase I study of dose-dense alternating doublets in advanced non-small-cell lung
      cancer.
AB  - We performed a study to determine the feasibility of a rapidly alternating
      administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in
      the treatment of advanced non-small-cell lung cancer (NSCLC). Thirty-four
      patients with NSCLC (6% stage IIIB, 94% stage IV) were enrolled. The initial
      schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28
      days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23
      28. Despite dose reductions, this sequence was not feasible. Therefore, the
      sequence was switched to give DG before CV, cycle duration was extended to 35
      days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia
      were dose-limiting toxicities. The recommended doses for phase II studies are
      docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60
      mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G
      CSF 5 microg/kg on days 2-7 and 23-28. However, treatment delays were required in
      subsequent cycles due to cumulative myelosuppression. A less intensive schedule
      is recommended for subsequent cycles for further testing. Overall response rate
      was 29% (95% confidence interval [CI], 14%-45%), and median survival for all
      patients was 11.8 months. One- and 2-year survival rates were 47% (95% CI, 30%
      63%) and 14% (95% CI, 1.4%-40%), respectively. Although initial administration of
      this regimen was feasible, dose intensity could not be maintained in subsequent
      cycles due to cumulative myelosuppression. A sequential rather than alternating
      use of doublet regimens might be more readily feasible and may permit greater
      maintenance of dose intensity.

PMID- 14662036
TI  - The future of cyclooxygenase-2 inhibitors and other inhibitors of the eicosanoid
      signal pathway in the prevention and therapy of lung cancer.
AB  - Recent advances in the understanding of the biology and molecular biology of lung
      cancer has provided targets for novel therapeutic and chemoprevention strategies.
      The eicosanoid/prostaglandin signal pathway is involved in the metabolism of
      membrane phospholipids to end products that are involved in apoptosis,
      proliferation, differentiation, and angiogenesis. Abnormalities in this pathway
      occur frequently in lung cancer, including the overexpression of cytoplasmic
      phospholipase A2, cyclooxygenase-2 (COX-2), prostaglandin E (PGE) synthase, PGE2,
      5-lipoxygenase (LOX), 8-LOX, and 12-LOX. Increased levels of PGE2, 5-LOX, 8-LOX,
      and 12-LOX promote tumor proliferation and angiogenesis and inhibit apoptosis. On
      the other hand, levels of proapoptotic, antiangiogenic, and antiproliferative
      products are frequently decreased in lung cancer due to decreased levels of
      enzymes such as prostacyclin synthase. These abnormalities provide a rationale
      for the use of inhibitors of overexpressed enzymes or replacement of
      anticarcinogenic end products, and such agents have been studied in preclinical
      and clinical trials.

PMID- 14662038
TI  - Extensive-stage small-cell lung cancer: is the progress real?

PMID- 14662040
TI  - Docetaxel plus cisplatin combinations in advanced non-small-cell lung cancer.

PMID- 14662039
TI  - Highlights from: The 2001 European Cancer Conference, Lisbon, Portugal, October
      21-25, 2001.

PMID- 14662041
TI  - Clinical benefits of epoetin alfa therapy in patients with lung cancer.
AB  - A retrospective subset analysis of anemic lung cancer patients who participated
      in three large, multicenter, community-based studies of 3-times-weekly (TIW) or
      once-weekly (QW) recombinant human erythropoietin (r-HuEPO, epoetin alfa) as an
      adjunct to chemotherapy was conducted. Patients were treated with epoetin alfa
      150 U/kg in the first TIW study and with 10,000 U subcutaneously in the other
      study, with doubling of the dose if hemoglobin (Hb) response was inadequate.
      Patients in the QW study received epoetin alfa 40,000 U subcutaneously, which
      could be increased to 60,000 U. The maximum treatment duration for all three
      studies was 16 weeks. A total of 1748 lung cancer patients were evaluable for
      hematopoietic response; 1298 were evaluable for analyses of energy and 1300 were
      evaluable for analyses of activity and overall quality of life (QOL), as measured
      by the linear analogue scale assessment (LASA). Within 2 months of therapy, TIW
      and QW epoetin alfa therapy resulted in significant increases in Hb levels,
      decreases in transfusion requirements, and improvements in self-reported LASA
      scores. Increased Hb levels and reduced transfusion rates were demonstrated in
      the individual studies and in the analysis of data pooled from all three studies.
      Improvements in QOL parameters were significantly correlated with increased Hb
      levels. Epoetin alfa was well tolerated in all studies. The clinical benefits and
      safety profiles of the TIW and the QW schedules appear to be similar. In
      addition, the QW schedule provides greater convenience to patients and physicians
      alike. Given the high incidence of anemia and transfusion utilization in patients
      presenting with lung cancer, epoetin alfa is an effective strategy for correcting
      anemia in these patients, thereby improving their energy levels, activity levels,
      and overall QOL.

PMID- 14662042
TI  - The treatment of unresectable, locally advanced non-small-cell lung cancer: a
      radiation therapy perspective with an emphasis on the trials of the Radiation
      Therapy Oncology Group.
AB  - Radiation therapy used as a single modality in the treatment of locally advanced
      non-small-cell lung cancer is potentially curative, but long-term survival rates
      are disappointing due to both locoregional and distant failures. The trials of
      the Radiation Therapy Oncology Group (RTOG) have been instrumental in defining
      the optimal management of this disease. The conclusions and questions posed by
      the RTOG are discussed in this review. The conclusions of this review include the
      following: chemotherapy combined with radiation therapy improves survival in
      patients with good performance, with increased toxicity; concurrent
      chemoradiation is superior to sequential chemoradiation. Questions remain
      regarding the value of the addition of induction or consolidation chemotherapy to
      concurrent chemoradiation, the value of three-dimensional conformal radiation
      therapy, the role of altered fractionation regimens in combination with
      chemotherapy, the optimal chemotherapeutic regimen, and the role of novel
      biologic agents.

PMID- 14662043
TI  - A retrospective analysis comparing patients 70 years or older to patients younger
      than 70 years with non-small-cell lung cancer treated with surgery at Indiana
      university: 1989-1999.
AB  - Surgery remains the cornerstone of therapy for medically operable patients with
      early-stage non-small-cell lung cancer (NSCLC). However, there are few reports on
      the short-term morbidity and long-term survival following surgery in elderly
      patients with NSCLC. The surgical experience in 280 patients with NSCLC at
      Indiana University from 1989-1999 are reported with a comparison of patients who
      are >or= 70 years versus < 70 years of age. Preoperative characteristics,
      operative procedures, postoperative courses, and survival were compared between
      the age groups. Fifty percent of elderly patients had squamous cell carcinoma and
      36.2% had adenocarcinoma, versus 41.3% and 44.4% in younger patients,
      respectively. In both groups, most patients had T1 or T2 tumors and N0 disease.
      The majority of patients in both age groups had a lobectomy. However, more
      patients younger than 70 years had chest wall resections and were more likely to
      undergo a pneumonectomy (19.5% vs. 6.9%). The median number of postoperative
      hospital days was shorter for younger patients (9 days vs. 11 days). Overall,
      more complications occurred in older patients, but no significant difference in
      cardiac or pulmonary complications was observed between the groups. There was no
      significant difference in survival between the age groups. This single
      institution series demonstrates that surgical intervention for appropriately
      selected elderly patients with NSCLC results in similar complication rates and
      long-term survival when compared to their younger counterparts.

PMID- 14662044
TI  - Novel doublets in extensive-stage small-cell lung cancer: a randomized phase II
      study of topotecan plus cisplatin or paclitaxel (CALGB 9430).
AB  - Chemotherapy for extensive-stage small-cell lung cancer (E-SCLC) produces high
      response rates and improved survival but few cures. We tested three new regimens
      for E-SCLC that might merit further investigation in a subsequent phase III
      trial. Cancer and Leukemia Group B 9430 was a randomized phase II study
      evaluating 4 treatment arms in 57 evaluable, previously untreated E-SCLC
      patients. Each arm consisted of the following: Arm 1: cisplatin plus topotecan;
      Arm 2: cisplatin plus paclitaxel; Arm 3: paclitaxel 230 mg/m2 plus topotecan; and
      Arm 4: paclitaxel 175 mg/m2 plus topotecan. Because of an accrual time
      difference, Arm 2 will not be discussed in this manuscript. Arm 1 (12 patients)
      produced 1 complete response (CR, 8%) and an overall response rate (ORR) of 42%.
      Toxicity was excessive, with 3 deaths (25%). Arm 3 (13 patients) produced no CRs,
      7 partial responses (PRs, 54%), median survival of 13.8 months, and failure-free
      survival (FFS) of 7.41 months, with 3 toxic deaths (25%). Among 32 evaluable
      patients on Arm 4, there were 2 CRs (6%) and 20 PRs (63%) for an ORR of 69%,
      median survival of 9.9 months, FFS of 5.21 months, and 1-year survival of 40%.
      There was 1 possible treatment-related death (3%). Topotecan plus cisplatin, in
      the doses and schedule employed, produced excessive toxicity and modest efficacy
      in E-SCLC patients. Paclitaxel (230 mg/m2 on day 1) plus topotecan (1 mg/m2 on
      days 1-5) produced excessive toxicity that was ameliorated with an attenuated
      paclitaxel dose (175 mg/m2). With the latter regimen (Arm 4) in patients with a
      performance status of 0/1, CR rates, FFS, overall survival, and 1-year survival
      were similar to standard etoposide plus cisplatin chemotherapy. Further
      exploration of topoisomerase inhibitors and taxanes in SCLC patients is
      warranted.

PMID- 14662046
TI  - Role of small-molecule kit receptor tyrosine kinase inhibitors in the treatment
      of small-cell lung cancer.
AB  - The prognosis of extensive-stage small-cell lung cancer (SCLC) has changed little
      in the past 3 decades, despite the documentation of high response rates to
      multiple chemotherapeutic regimens. Increasing the dose or the dose intensity of
      standard chemotherapy has increased toxicity without a significant improvement in
      outcome. However, our understanding of the biology of this disease has
      dramatically changed over the past 30 years, and this understanding has resulted
      in the identification of novel therapeutic targets. Evidence supporting the Kit
      growth factor receptor tyrosine kinase as a therapeutic target in SCLC is
      detailed. The properties of small-molecule Kit inhibitors currently in clinical
      development, as well as their efficacy in preclinical SCLC studies, are
      presented. The rationale for combining small-molecule Kit inhibitors with
      standard chemotherapy in clinical trials for extensive-stage SCLC is discussed.

PMID- 14662047
TI  - A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer.
AB  - This study was designed to evaluate the efficacy and toxicity of the immunotoxin
      N901-blocked ricin (bR) in patients with small-cell lung cancer (SCLC) who
      achieved a complete or near-complete response following chemotherapy and/or
      radiation. Treatment consisted of a 7-day continuous infusion of N901-bR at a
      dose of 30 mg/kg/day followed by patient evaluation with repeat scans. Serum
      immunotoxin levels, human antimurine antibodies, and antiricin antibodies were
      determined during the course of the infusion. Nine patients enrolled in the study
      before it closed following a treatment-related death. Seven patients had
      extensive-stage disease and entered the study with a more than 90% reduction of
      their original tumor. Two patients with limited-stage SCLC had no evidence of
      disease at study entry. Maximum plasma levels of N901-bR ranged from 72-371
      ng/mL. Laboratory toxicity consisted of transient transaminitis in 8 patients and
      creatine kinase elevation in 3 patients, 1 of whom developed premature
      ventricular contractions. One patient experienced progressive capillary leak
      syndrome following immunotoxin infusion, which proved fatal. All patients
      developed antibodies to the infused murine antibody as well as to the toxin. Six
      patients died of progressive SCLC and 1 patient died of presumed radiation
      pneumonitis. One patient with limited-stage disease is still alive more than 6
      years after therapy. N901-bR therapy was associated with a fatal incident of
      capillary leak syndrome and a nearly universal development of human antimouse and
      antiricin antibodies, which limited its further clinical development.

PMID- 14662048
TI  - Child protection issues and sexual health services in the UK.

PMID- 14662049
TI  - Progestogens and breast cancer risk: the role of hormonal contraceptives and
      hormone replacement therapy.

PMID- 14662050
TI  - Men's use of sexual health services.
AB  - CONTEXT AND OBJECTIVE: Previous research on users of sexual health services has
      focused primarily on women. However, a focus on men also is needed to address
      sexual ill-health. This paper uses various data sources to describe the level of,
      and trends in, men's use of sexual health services in England. DATA SOURCES:
      Routine data are presented on clients of family planning clinics (FPCs), Brook
      Advisory Centres and attendances at genitourinary medicine (GUM) clinics. Cross
      sectional surveys used include the National Survey of Sexual Attitudes and
      Lifestyles, Morbidity Statistics from General Practice and the National Gay Men's
      Sex Survey. RESULTS: The number of male clients attending FPCs has increased by
      160% over the 1990s. Most of this increase is due to more men obtaining condoms.
      The ages of these clients are unknown, but data from Brook Advisory Centres show
      an increase among younger men. The one service for which male and female use is
      approximately equal is GUM. Male cases of sexually transmitted infections and
      other treatments have increased over the 1990s, although not at the same rate as
      female cases. Use of GUM clinics by homosexually active men is much greater than
      by all men. Recent data on men's use of general practice for sexual health are
      lacking. DISCUSSION AND CONCLUSIONS: While overall service use among men is still
      at a comparatively low level, it has increased over the 1990s for some services.
      Further in-depth research should question men's wants and demands from sexual
      health services.

PMID- 14662051
TI  - Promoting sexual health services to young men: findings from focus group
      discussions.
AB  - CONTEXT: Recently, increasing interest has been shown in men's reproductive
      health, sexual behaviour and use of contraception. As the majority of sexual
      health service clients are female, however, little research has been done on the
      characteristics and needs of male clients. OBJECTIVE: Using data from focus group
      discussions, this paper considers whether young men need sexual health services,
      whether current services are appropriate and accessible, and what promotion
      strategies might increase service uptake. DESIGN: Nine focus group discussions
      with 75 men aged 13-21 years at different locations in England. RESULTS: Young
      men's decision-making around sexual health may involve seeking advice from a
      close friend, but is less likely in some male social groups. Use of services by
      young men is most likely to obtain free condoms, or to remedy a crisis situation.
      While a young man is becoming familiar with obtaining condoms from a service, the
      need for a quick, straightforward service seems important. The stereotypical view
      within the groups was that sexual health services are women-oriented. However,
      suggestions are given to make services more youth- and male-friendly. Promotion
      should aim to increase awareness and advance a positive image of a sexual health
      service. DISCUSSION AND CONCLUSIONS: Effective promotion campaigns (designed with
      the input of local young men), combined with appropriate and accessible services,
      should help to increase service use among young men.

PMID- 14662052
TI  - Barriers to the involvement of clients in family planning service development:
      lessons learnt from experience.
AB  - CONTEXT: Client involvement in service development underpins the Department of
      Health strategy for sexual health improvement in the UK. Participatory approaches
      to user consultation have been effectively piloted in this context but the
      responses of service providers to these data are rarely documented. OBJECTIVES:
      Recruiting clinic users and training clinic users to interview their fellow
      clinic users on sexual health service use and to document staff responses to the
      results of this consultation. DESIGN: Clinic users interviewed young clinic users
      (aged <25 years) using a time line to generate a description of their first
      clinic visit. The results were presented to staff with a questionnaire requesting
      their views. RESULTS: Forty-six clients were interviewed. More comments were made
      on the waiting room than any other aspect of clinic use. These comments were
      almost exclusively negative. The waiting room was described as uncomfortable,
      insufficiently confidential and lacking refreshment and entertainment. Most
      clients were happy with the clinical consultation. Both positive and negative
      comments on this aspect of service use related to staff attitudes. The priorities
      of clients and staff were different and potentially conflicting. Whereas staff
      are keen that the waiting room should appear tidy, clients require refreshments
      or children's toys that generate mess. Staff see the clinical service as the most
      important aspect of a clinic visit while users may view their comfort while
      waiting for long periods as equally important. DISCUSSION: This methodology
      documents clients' experiences (positive and negative) of a specific service and
      generates practical suggestions for improvement. Further work is required to
      identify common goals for staff and clients. An iterative process of staff and
      client consultation may ensure that future service development proceeds in a
      direction that meets the needs of both groups.

PMID- 14662053
TI  - Access by the unaccompanied under-16-year-old adolescent to general practice
      without parental consent.
AB  - BACKGROUND: The views of primary health care providers concerning their
      willingness to consult with under-16-year-old adolescent patients without the
      presence of a parent or guardian are not well documented. Many young people
      believe they have to be aged over 16 years to see their general practitioner (GP)
      alone. Confidentiality is a major concern for young people. It is important that
      more is known about the willingness of GPs and practice nurses (PNs) to offer
      unaccompanied consultations without known parental consent. AIM: To provide
      information on the willingness of GPs and PNs to consult with under-16-year-olds
      and whether policies exist in general practices to facilitate access by
      unaccompanied under-16-year-olds. STUDY DESIGN: Cross-sectional study using a
      postal questionnaire. SETTING: Seventeen general practices in the West of
      Cornwall. METHOD: All GPs, PNs and receptionists were sent questionnaires.
      RESULTS: The overall response rate was 79% (166/209 questionnaires). The majority
      of GPs and PNs (91%) were willing to consult with unaccompanied under-16-year
      olds. A substantial number of primary health care team members are not aware of
      the existence of any practice policy on access. Only 41% of receptionists, 46% of
      PNs and 38% of GPs were aware of a definite practice policy. CONCLUSIONS: GPs and
      PNs are willing to consult with under-16-year-olds without a parent or guardian
      being present. Many practices in this region do not appear to have policies in
      place to guide health professionals on under-16 access issues.

PMID- 14662054
TI  - FFPRHC Guidance (October 2003): First prescription of combined oral
      contraception.
AB  - The Guidance provides information for clinicians on the steps to be taken before
      providing a woman with her first prescription for combined oral contraception. It
      updates and replaces previous Faculty Guidance. A key to the grades of
      recommendations, based on levels of evidence, is given at the end of this
      document. Details of the methods used by the Clinical Effectiveness Unit (CEU) in
      developing this Guidance, and evidence tables summarising the research basis of
      the recommendations, are available on the Faculty website (www.ffprhc.org.uk).
      Abbreviations used include: blood pressure (BP), body mass (BMI), bone mineral
      density (BMD), breakthrough bleeding (BTB), British National Formulary (BNF),
      combined oral contraception (COC), Committee on Safety of Medicines (CSM),
      confidence interval (CI), deep vein thrombosis (DVT), emergency contraception
      (EC), ethinyl oestradiol (EE), Faculty Aid to Continuing Professional Development
      Topics (FACT), Family Planning Association (fpa), follicule-stimulating homone
      (FSH), general practitioner (GP), intermenstrual bleeding (IMB), luteinising
      hormone (LT), microgram, myocardial infarction (MI), odds ratio (OR), oral
      contraception (OC), pulmonary embolism (PE), relative risk (RR), Scottish
      Intercollegiate Guideline Network (SIGN), sexually transmitted infection (STI),
      Summary of Product Characteristics (SPCs), venous thomboembolism (VTE), World
      Health Organization (WHO), WHO Medical Eligibility Criteria (WHOMEC), WHO
      Selected Practice Recommendations (WHOSPR).

PMID- 14662056
TI  - The members' enquiry service: frequently asked questions.

PMID- 14662057
TI  - Intrauterine device insertion-related complications: can they be predicted?
AB  - OBJECTIVE: To determine risk factors affecting the incidence of intrauterine
      device (IUD) insertion-related complications and failures and, in particular,
      whether postcoital IUD insertions have a higher incidence of complications than
      routine IUD insertions. DESIGN: Retrospective case notes analysis. PARTICIPANTS:
      The study examined 545 case notes of patients having IUD insertions at East
      Cheshire NHS Trust family planning clinics between 1 October 1997 and 31 December
      2000. MAIN OUTCOME MEASURES: The incidence of complications at insertion, or up
      to 12 weeks after insertion, was determined and included failed insertion,
      cervical problems, syncope, bradycardia, convulsions, early perforation and early
      expulsion. Fourteen potential risk factors were examined to determine the effect
      on incidence of complications. RESULTS: Failed insertions were statistically more
      likely in women who had never previously had a vaginal delivery and also when a
      less experienced doctor performed the insertion. Nulliparous women were at
      statistically increased risk of cervical problems and bradycardia. Cervical
      problems at insertion also increased significantly with age. Patients who were
      amenorrhoeic at insertion were more likely to suffer an early IUD expulsion.
      CONCLUSIONS: Of the potential risk factors, nulliparity was the most important.
      IUD insertion failures and complications were no more common in postcoital than
      routine IUD insertions. In general, complications were unpredictable, indicating
      the need for constant vigilance and the inserting doctor being trained and
      prepared to deal with any complication arising.

PMID- 14662058
TI  - A review of controlled trials of acupuncture for women's reproductive health
      care.
AB  - BACKGROUND: Acupuncture as a therapy, and acupressure as self-treatment, are
      increasingly widely used for gynaecological conditions, and this study aims to
      review the scientific literature on their effectiveness. METHOD: A systematic
      review of controlled trials of acupuncture or acupressure for gynaecological
      conditions, published in a European language. SYNTHESIS: No studies in mastalgia,
      menorrhagia, pelvic pain, premenstrual syndrome or vulvodynia met the inclusion
      criteria. Four studies, two of which were patient-blinded, of acupuncture or
      acupressure for dysmenorrhoea suggest that it may have an effect. Three studies
      of acupuncture given at various stages of infertility treatment are promising,
      but none was patient-blind. Two studies of acupuncture for menopausal symptoms
      showed no effect during the treatment period when compared with sham acupuncture,
      and a third study showed no effect on hypertension in postmenopausal women,
      though some improvement in symptoms was noted. CONCLUSION: In view of the small
      number of studies and their variable quality, doubt remains about the
      effectiveness of acupuncture for gynaecological conditions. Acupuncture and
      acupressure appear promising for dysmenorrhoea, and acupuncture for infertility,
      and further studies are justified.

PMID- 14662059
TI  - Intravesical migration of a GyneFix intrauterine device.
AB  - A case of intravesical migration of a GyneFix intrauterine device (IUD) is
      described, in which the patient presented with supra-pubic pain and urinary
      symptoms. The diagnosis was made 34 months after the insertion of the IUD, by
      ultrasound scan. The GyneFix was removed endoscopically. A description of the
      GyneFix device, the possible adverse effects and incidences of its complications,
      the importance of post-insertion follow-up, and the need for awareness of the
      possibility of intravesical migration are discussed.

PMID- 14662060
TI  - Spontaneous snapping of an Implanon in two halves in situ.
AB  - A 30-year-old woman presented at our family planning clinic for Implanon removal
      and reinsertion. At the time of presentation the patient's weight was 148 kg. The
      Implanon was fitted in July 2000 (i.e. 35 months previously) when her weight was
      138.5 kg. The patient was very happy with the contraceptive method. She was aware
      that her Implanon had snapped in half about 2 months ago. There was no
      aggravating factor such as weightlifting associated with this incidence.

PMID- 14662061
TI  - Infertility treatment for HIV-positive couples: far from immaculate conception.

PMID- 14662062
TI  - Report from the Faculty of Family Planning and Reproductive Health Care AGM, May
      2003: Medical termination of pregnancy in the late first trimester.
AB  - In the UK, mifepristone and gemeprost are licensed for medical termination of
      pregnancy (TOP) in the first trimester up to 63 days' amenorrhoea. Current
      practice, however, is to use low-dose (200 mg) mifepristone and misoprostol. We
      report a large cohort study using these drugs for medical TOP in the first
      trimester after 63 days amenorrhoea. Of 415 patients undergoing the procedure,
      392 (95%) aborted completely and 96% required only two doses of misoprostol. We
      conclude that the regime is effective with few complications, however certain
      safeguards may be necessary for its widespread introduction

PMID- 14662063
TI  - Evidence-based reproductive health care: using evidence about diagnostic tests.

PMID- 14662065
TI  - Ectopic pregnancy following use of progestin-only ECPs.

PMID- 14662064
TI  - Pharmacists and POEC.

PMID- 14662071
TI  - Rapid changes in lifestyle make increased physical activity a priority for the
      Americas.

PMID- 14662073
TI  - [The effect of controlled physical activity on the body composition of
      postmenopausal sedentary women].
AB  - OBJECTIVE: To evaluate the effect of a controlled physical activity program on
      the weight and body composition of healthy sedentary postmenopausal women.
      METHODS: From a group of 138 postmenopausal women volunteers, 18 of them were
      selected, using a survey that measured the frequency and intensity of their
      physical activity. These 18 women were classified as "sedentary," having an
      average daily energy expenditure (in terms of mL of oxygen per kg per minute)
      that was below 60% of the maximum oxygen consumption for their age. These 18
      women underwent a general physical examination, laboratory tests, and spirometry
      to make certain that they did not have illnesses that would prevent them from
      participating in the planned controlled physical activity program. The activity
      program lasted 4 months, with three one-hour sessions per week. Before and after
      the program the following characteristics were evaluated for each participant:
      weight, body fat, and the fatty area and the lean area of the arm, the thigh, and
      the leg. In addition, energy intake was determined based on a record of food
      consumption, with the frequency of the consumption of specific foods assessed
      semiquantitatively. The Student's t test was used to compare the averages for all
      the measurements before and after the exercise program. When the variables did
      not have a normal distribution, the Wilcoxon signed rank sum test was utilized.
      RESULTS: At the end the program we found a reduction of 1.2 kg in weight and of
      2.0 kg in body fat, while the lean mass increased by 1.0 kg. Also increasing were
      the lean area of the arm, of the thigh, and of the leg; the areas of fat in those
      parts of the body decreased. The differences were statistically significant for
      all the variables observed except for the lean area of the thigh. There were no
      significant differences between the women's energy intake at the beginning and
      the end of the program. CONCLUSIONS: The controlled physical activity program
      improved the body composition of this group of women, decreasing the fat deposits
      and increasing the lean body mass.

PMID- 14662074
TI  - [Factors associated with physical activity among Mexican women of childbearing
      age].
AB  - OBJECTIVE: To document the practice of light and heavy physical activities,
      especially sports and exercise, among women from 12 to 49 years old in Mexico,
      and to evaluate the association that that has with some sociodemographic
      characteristics. METHODS: A sample of 2 367 women 12 to 49 years old living in
      Mexico in 1999 was studied through secondary analysis of data from Mexico's 1999
      National Nutrition Survey (Encuesta Nacional de Nutricion). The Survey used a
      clustered stratified multistage sampling scheme, with a final sample of 21 000
      homes in the entire country. A questionnaire was used to evaluate the time that
      the women spent on various forms of physical activity, with the activity measured
      on a scoring scale in terms of metabolic equivalents (METs). The dependent
      variables in the study were the time spent on heavy physical activities (those
      that require an energy expenditure of at least 5 METs/hour) and the time devoted
      to light or sedentary activities (such as sitting while on the job or elsewhere;
      watching television, a video, a movie, or a theater presentation; or sleeping).
      The independent variables were age, schooling, parity, region of the country,
      area of residence (urban or rural), socioeconomic level (measured through an
      index prepared based on housing conditions and household possessions), and
      marital status. The association between the independent variables and practicing
      sports was evaluated, and gross odds ratios (ORs) were calculated, with 95%
      confidence intervals (CIs). In order to identify the association between
      practicing sports and the independent variables a logistic regression model was
      used, adjusted for the effects of possible confounding variables. Adjustments
      were also made in the probability of a woman's being selected for the sample,
      using a weighting factor. In addition, adjustments were made to control for the
      design effect produced by the grouping of the observations in the sample, using
      the "svy" complex-samples routine of the Stata version 7.0 statistical analysis
      computer software. RESULTS: The 2 367 women whose information was analyzed spent
      an average of 0.08 hours per day practicing sports and 1.25 hours per day on
      heavy physical activities. Only 16% of the women reported that they regularly
      practiced some sport. After adjusting for all the independent variables, the
      women older than 30 years had a lower OR of practicing sports in comparison to
      women who were 20 years of age or less (OR = 0.53; 95% CI: 0.33 to 0.84), as was
      also true for women 21-30 years old (OR = 0.35; 95% CI: 0.23 to 0.54). Having the
      highest level of schooling and not having had children were both directly
      associated with practicing a sport. While the area of residence (urban or rural),
      marital status, and socioeconomic level showed differences among the groups, such
      differences were not significant after adjusting for the other study variables.
      In terms of physical activity measured in METs, the time spent on sports made up
      10% of the total for heavy activity and 0.7% of the overall total. In terms of
      the possibility of being among the 10% of the women who expended the fewest METs
      per day, that was more likely for women under 21 years of age than it was for
      women 31 or older, and it was also more likely for women who had a primary level
      of schooling than for women with a secondary education. CONCLUSIONS: This study
      showed that practicing sports is not a frequent form of physical activity among
      women of childbearing age in Mexico, especially those who are over 20 years of
      age and those with a low level of schooling. This situation could contribute to
      increases in the prevalence of obesity and chronic diseases.

PMID- 14662075
TI  - A descriptive epidemiology of leisure-time physical activity in Brazil, 1996
      1997.
AB  - OBJECTIVES: To describe the prevalence, frequency, type, motivation for, and
      demographic and socioeconomic distribution of leisure-time physical activity
      (LTPA) among adults in Brazil. METHODS: The data source for our study was the
      Brazilian Living Standards Measurement Survey (LSMS) (Pesquisa sobre Padroes de
      Vida), which was conducted in 1996 and 1997. This survey studied a multistage
      stratified probabilistic sample of 4 893 households, which included 11 033
      persons who were 20 years of age or older. The surveyed households were selected
      in the two most populous Brazilian regions, the Northeast and the Southeast,
      where in total 70% of all Brazilians live. The selected persons responded to a
      series of questions concerning their leisure-time physical activities. RESULTS:
      Only 13% of the Brazilians surveyed reported performing at least a minimum of 30
      minutes of LTPA on one or more days of the week, and only 3.3% reported doing the
      recommended minimum of 30 minutes on 5 or more days of the week. In younger age
      groups, men were more active than were women. However, this difference sharply
      decreased with increasing age, and by the age range of 40 to 45 years the
      prevalence of LTPA was similarly low in both genders. Men reported engaging in
      more team sports, and women reported more walking/jogging activities, but
      walking/jogging was relatively more common in both genders when physical activity
      was performed on 5 or more days of the week. Recreation was by far the leading
      reason given by men to engage in LTPA, while recreation, health concerns, and
      even esthetic concerns were all relevant for women. In both genders, health
      concerns tended to be relatively more important for those exercising more days of
      the week. Also in both genders, increasing age was associated with more frequent
      LTPA, more walking/jogging than team sports, and more health concerns reasons
      than reasons related to recreation. Among both men and women there was a strong
      association between LTPA and socioeconomic status, measured either by income or
      schooling, independent of age, region, and urban or rural place of residence.
      CONCLUSIONS: The prevalence of adult LTPA in Brazil was much lower than the
      levels that have been reported for developed countries. However, the demographic
      and social distribution of LTPA in Brazil followed a pattern similar to the one
      usually observed in developed nations, where men tend to be more active than
      women, increasing age limits LTPA, and higher socioeconomic status is associated
      with more LTPA. Our data will provide a baseline to evaluate the impact on LTPA
      of "Agita Brasil" ("Move, Brazil"), an initiative to encourage physical activity
      that was implemented in the country after 1997.

PMID- 14662076
TI  - [Sociodemographic and environmental factors associated with sports physical
      activity in the urban population of Peru].
AB  - OBJECTIVES: To determine the frequency of sports physical activity in the urban
      population of Peru and to identify the sociodemographic, economic, and
      environmental factors associated with that activity. METHODS: This study utilized
      information collected by the country's National Household Survey (Encuesta
      Nacional de Hogares) in the second quarter of 1997. That Survey is overseen by
      Peru's National Institute of Statistics and Informatics (Instituto Nacional de
      Estadistica e Informatica). The Survey was based on a probabilistic, multistage
      sample that was stratified for all the urban areas of the country, which was
      divided into eight geographic regions: metropolitan Lima, northern coast, central
      coast, southern coast, northern mountains, central mountains, southern mountains,
      and jungle. In total, 14 913 homes were visited and 45 319 people at least 15
      years of age were interviewed. The frequency of engaging in sports physical
      activity was classified as daily, every other day, weekly, or occasional.
      "Regular sports activity" (RSA) was defined as engaging in sports either every
      day or every other day. The preferences for and obstacles to sports practice were
      also examined. A descriptive analysis of the levels of RSA was carried out for
      gender, using the chi-square test. The factors associated with RSA were analyzed
      through conditional multiple logistic regression and analysis of residuals,
      multicollinearity, and interactions. The level of significance was set at P <
      0.05. RESULTS: Practicing sports at least once a week was more common among men
      (44.5%) than among women (32.4%), and the same was true for RSA (12.8% versus
      10.5%). The age group with the highest level of RSA was 50-55 years for men
      (20%), and 40-45 years for women (18%). RSA was most common in three geographic
      regions: jungle (15.3%), central mountains (12.8%), and central coast (12.1%).
      RSA was least common in two regions: southern mountains (9.7%) and metropolitan
      Lima (10.6%). The income bracket was not associated with RSA. However, other
      variables associated indirectly with the socioeconomic level - such as having
      more formal education, being employed, and having access to the Internet or cable
      television - and consumption of sports information were significantly and
      directly associated with RSA. The most frequent barriers to practicing sports
      were the lack of time, the lack of nearby sports infrastructure (playing fields
      or courts, etc.), and people's lack of interest. RSA on the part of the members
      of a household was significantly associated with RSA performed by the head of the
      household (male or female). CONCLUSIONS: RSA is limited in the urban areas of
      Peru. This is most true for persons who are less than 30 years old, for women,
      and for residents of the Lima metropolitan area. This low RSA level is a
      challenge for public health, and it confirms the need for promoting active
      lifestyles. More study is needed on the observed positive influence when the head
      of the household performs RSA and on the fact that RSA is more common in urban
      areas outside metropolitan Lima. These two findings should also be taken into
      consideration in designing specific interventions.

PMID- 14662077
TI  - The Agita Sao Paulo Program as a model for using physical activity to promote
      health.
AB  - The "Agita Sao Paulo" Program applies a multilevel intervention approach to
      promoting physical activity among the 37 million inhabitants of the state of Sao
      Paulo, Brazil. The verb "agita" means to move the body, but the term also
      suggests changing the way of thinking and becoming a more active citizen. Since
      being launched in 1996, the Program has been widely copied throughout Brazil and
      in other countries of Latin America, and the World Health Organization has
      characterized it as a model for other developing countries. The Program aims to
      disseminate a clear and simple message to the community as well as establish
      partnerships with governmental and nongovernmental organizations and other
      entities. The Agita Sao Paulo message encourages people to adopt an active
      lifestyle by accumulating at least 30 minutes of moderate physical activity per
      day, on most days of the week. The Program has three main target groups:
      students, workers, and the elderly. The Program organizes "mega-events" that
      simultaneously reach and involve large numbers of people, and it also conducts
      ongoing activities with institutions that become partners of the Program.
      Intervention studies that the Program has carried out on specific, small groups
      have found both changes in behavior and an increasing awareness of the Program's
      name and message. In addition, surveys have found that a growing number of
      persons in the state of Sao Paulo have become aware of the Program and its
      message and have changed their physical activity level. A number of the special
      features of and lessons learned from the Agita Sao Paulo Program may have
      contributed to its success, including: a multisectorial approach; broad use of
      partnerships; the inclusion principle (avoiding messages or attitudes that might
      exclude any social group); the scientific basis for all the Program activities;
      the extensive free media coverage that the Program has received; a "two-hats"
      approach, using either governmental or nongovernmental methodologies to promote
      physical activity, depending on the circumstances; cultural adaptation (using
      local culture to disseminate the message and make its assimilation easier);
      encouraging activities that are pleasurable; the clear, simple, feasible message
      of promoting physical activity; and evaluation of the various Program efforts.
      These distinctive characteristics help make the Agita Sao Paulo Program a model
      that could be used in other countries as an effective way to promote health
      through physical activity.

PMID- 14662079
TI  - [Promoting health and physical activity in Chile: a policy priority].

PMID- 14662080
TI  - [Report looks at physical activity in both work and leisure time in the United
      States].

PMID- 14662081
TI  - Employers in the United States promote healthy lifestyles in order to reduce
      health care expenditures.

PMID- 14662092
TI  - Angioplasty or pharmacologic thrombolysis or both for ST-elevation myocardial
      infarction: the current debate.

PMID- 14662093
TI  - An overview of contemporary nuclear cardiology.
AB  - Myocardial perfusion single photon emission computed tomography (SPECT) is a
      widely utilized noninvasive imaging modality for the diagnosis, prognosis, and
      risk stratification of coronary artery disease. It is clearly superior to the
      traditional planar technique in terms of imaging contrast and consequent
      diagnostic and prognostic yield. The strength of SPECT images is largely derived
      from the three-dimensional, volumetric nature of its image. Thus, this modality
      permits three-dimensional assessment and quantitation of the perfused myocardium
      and functional assessment through electrocardiographic gating of the perfusion
      images.

PMID- 14662094
TI  - Recent advances in cardiac positron emission tomography in the clinical
      management of the cardiac patient.
AB  - Despite being primarily a research tool, positron emission tomography (PET) has
      seen slow but steady growth in the clinical management of the cardiac patient.
      The two major clinical applications of cardiac PET are regional myocardial
      perfusion imaging to determine the presence and severity of coronary artery
      disease and metabolic imaging to differentiate viable from nonviable myocardium
      in patients with ischemic left ventricular dysfunction. Indeed, PET with either
      nitrogen 13 ammonia or rubidium 82 may offer advantages over current single
      photon emission computed tomography approaches to assess myocardial perfusion.
      PET with fluorine 18 fluorodeoxyglucose is considered the current gold standard
      for identifying viable myocardium. Finally, the use of PET to quantify myocardial
      perfusion, metabolism, and innervation has led to key insights into the role of
      altered microvascular function, substrate metabolism, and neuronal function in a
      variety of cardiac disease processes.

PMID- 14662095
TI  - The clinical role of stress myocardial perfusion imaging in women with suspected
      coronary artery disease.
AB  - Cardiovascular disease remains the number one cause of mortality for women in the
      United States, with coronary artery disease (CAD) accounting for 54% of all
      cardiovascular deaths. CAD claims the lives of more than 250,000 women each year
      and is therefore the single largest killer of American women. For several
      decades, the under-representation of women in clinical trials led to both a lack
      of available sex-specific evidence and a generalized misconception that CAD was a
      "man's disease." In actuality, not only are women vulnerable to CAD, they
      typically develop it 10 to 15 years later than men. Furthermore, sex differences
      exist in the mortality rates of women and men with CAD, such that once CAD is
      present in women, they have worse outcomes than their male counterparts.
      Consequently, early and accurate diagnosis of CAD is crucial for reducing
      mortality rates in women. Stress myocardial perfusion imaging (MPI) using
      contemporary techniques has been shown to have significant value in the diagnosis
      and prognosis of CAD in women. In the risk assessment of women with an
      intermediate clinical pretest likelihood of CAD, using MPI with exercise or
      pharmacologic stress has been shown to add incremental value to clinical
      variables or exercise electrocardiogram stress testing alone. This review
      discusses the clinical role of stress MPI in the management of women with
      suspected CAD.

PMID- 14662096
TI  - Attenuation correction for single photon emission computed tomography myocardial
      perfusion imaging.
AB  - The specificity of cardiac single photon emission computed tomography (SPECT)
      perfusion imaging is significantly affected by internal photon absorption.
      Commonly referred to as anterior wall breast and inferior wall diaphragm
      attenuation artifacts, even when following characteristic patterns in women and
      men, the reduced activity produced can be difficult to differentiate from real
      perfusion defects. Unfortunately, wide variations in body habitus result in
      unpredictable variations in tissue attenuation and the specificity of uncorrected
      SPECT is unacceptably low in many laboratories. This manuscript reviews recent
      developments in attenuation correction methods for cardiac SPECT. Several
      commercial methods are now available, and although the initial success using
      these methods varied widely, as these methods have been improved successful
      clinical reports are appearing with increasing frequency. Recent developments
      have yielded more robust validated methods and significant clinical advantages
      have been achieved in the diagnostic evaluation of coronary heart disease
      (sensitivity as well as specificity) and myocardial viability. As these methods
      continue to mature, further advances should be anticipated.

PMID- 14662097
TI  - Cost efficiency of nuclear cardiology services in the modern health care
      environment.
AB  - More than a decade of dramatic changes in US and global health care has affected
      the practice of and payment for nuclear cardiology services. The clear diagnostic
      and prognostic power of nuclear cardiology procedures to detect coronary artery
      disease and predict patient outcomes has resulted in the rapid growth of these
      procedures in clinical practice. This has focused the attention of public and
      private payers on the high use of medical resources required to carry out nuclear
      cardiology testing. Two recent, major multicenter trials, one in the United
      States and another in Europe, have demonstrated the cost effectiveness of stress
      myocardial perfusion imaging strategies compared with coronary angiography in
      patients with known or suspected coronary artery disease, across the spectrum of
      pretest risks and both sexes. These studies, and more extensive data from more
      than 10 years of decision analysis, have reinforced the value of nuclear
      cardiology in modern cardiovascular health care. Future challenges will include
      assurance of provider and laboratory quality in the burgeoning outpatient imaging
      centers across the country, and wider acceptance by payers and expert panels of
      the evidence supporting the cost effectiveness of nuclear cardiology in most
      clinical settings.

PMID- 14662098
TI  - Imaging of ventricular function by cardiovascular magnetic resonance.
AB  - Over the past 15 years, cardiac magnetic resonance imaging (CMR) has vaulted to
      the forefront as the ideal diagnostic modality for the evaluation of both left
      and right ventricular function. The accumulated literature supports this
      contention for the left ventricle. However, for the right ventricle, typically
      poorly visualized accurately by traditional imaging techniques, CMR has emerged
      as the test of choice. Although earlier CMR sequences have become even more
      robust, resulting in further improvements in spatial and temporal resolution, CMR
      has avidly remained the gold standard. Yet, these attributes that have so
      benefited investigations of the systole need not be so constrained. In this
      review, we discuss recent applications of CMR to the study of lusitropy,
      demonstrating the potential for further advances in our understanding of
      diastole.

PMID- 14662100
TI  - Future prospects in magnetic resonance imaging.
AB  - Cardiovascular magnetic resonance (CMR) is widely regarded as capable of
      providing a cornucopia of detailed diagnostic information. However, of that
      information, very little is truly unique, and can be obtained by a combination of
      alternate diagnostic modalities. Given this, it is anticipated that in the short
      term (1-5 years) CMR will find use primarily as a modality to service patients
      whose diagnosis is inaccessible to established technologies such as ultrasound
      and radionuclide imaging. Due to the evolving emphasis on finding new and more
      efficient approaches to disease detection and prevention, as outlined in a policy
      setting speech given by the director of the National Institutes of Health, it is
      anticipated that the scientific and clinical trial communities will adopt CMR at
      a more rapid pace due to its inherent dimensional accuracy and comprehensive
      nature. CMR is particularly well suited to participate in the approaching
      explosion of nanoparticle technologies, as they are applied to diagnostic and
      therapeutic approaches. In the longer term (5-10 years), as paradigms of disease
      detection likely expand beyond evaluation of symptoms and risk factors, the
      comprehensive nature of information provided by CMR will drive the increase of
      its use as a primary, first-tier, diagnostic modality. In summary, the use of CMR
      will become increasingly common, and as understanding of disease processes
      expand, it will emerge as a diagnostic modality that provides an abundance of
      unique information.

PMID- 14662099
TI  - Assessment of myocardial ischemia and viability using cardiac magnetic resonance.
AB  - Cardiac magnetic resonance (CMR) is a burgeoning area of noninvasive cardiac
      imaging. Today, its clinical utility spans from the qualitative and quantitative
      assessment of cardiac function and morphology to the challenging task of
      determining the severity and reversibility of coronary heart disease. Advances in
      magnet and coil design, pulse sequence, and contrast media have contributed
      greatly, helping CMR become the multipurpose tool of today's cardiac imaging.
      This article reviews and explores some of the most exciting clinical applications
      of CMR in the assessment of coronary artery disease.

PMID- 14662101
TI  - Psychosocial factors and coronary heart disease.

PMID- 14662102
TI  - The ALLHAT-LLT and ASCOT-LLA trials: are the discrepancies more apparent than
      real?
AB  - During the past decade, numerous landmark trials of statins in secondary and
      primary prevention and their meta-analyses have demonstrated statistically
      significant and clinically important reductions in myocardial infarction, stroke,
      and vascular death (by about one third), as well as total mortality (by about one
      fifth). In the past year, two trials of statins have been reported among
      hypertensive subjects enrolled in blood pressure-lowering trials, one in the
      United States and the other in Europe. The US trial, the Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial--Lipid Lowering Trial
      (ALLHAT-LLT), was reported as showing no significant benefit. In contrast, the
      European trial, the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm
      (ASCOT-LLA), was terminated early based on the unanimous recommendation of the
      Data and Safety Monitoring Board, due principally to the emergence of a
      statistically extreme 36% reduction in the primary endpoint of nonfatal
      myocardial infarction and death from coronary heart disease (P<0.0005). These
      trial results have been viewed as discrepant, but methodologic issues of
      inadequate power of ALLHAT due to lower than projected sample size and poor
      compliance due to an open design render these discrepancies more apparent than
      real. The ALLHAT-LLT trial should be viewed not as null, but as uninformative, as
      the 95% confidence limits around the point estimate include the most plausible
      small to moderate benefit of statins. The totality of evidence on statins
      continues to strongly support their benefits in a wide range of patients on a
      large number of cardiovascular disease endpoints.

PMID- 14662103
TI  - New and emerging data from clinical trials of statins.
AB  - Recent clinical trials of statins have clearly demonstrated the benefit of statin
      therapy in preventing both coronary and cerebral vascular events. These benefits
      have been demonstrated to be present without reference to older age, sex, or
      comorbid conditions, including hypertension and diabetes. Future trials will test
      the value of more aggressive low-density lipoprotein cholesterol lowering, the
      value of immediate statin intervention during acute coronary syndromes, the role
      of cholesterol lowering with or without angioplasty, and the role of cholesterol
      lowering in stroke prevention.

PMID- 14662104
TI  - Noninvasive atherosclerosis imaging for predicting cardiovascular events and
      assessing therapeutic interventions.
AB  - Noninvasive assessment of atherosclerosis offers an opportunity to provide
      individual cardiovascular risk management and an opportunity to monitor the
      efficacy of therapy targeted toward atherosclerosis. The three imaging modalities
      that currently hold the most promise at the clinical and research levels are
      ultrasound for carotid intima-media thickness, computed tomography for coronary
      artery calcification, and magnetic resonance imaging for carotid and aortic
      plaque imaging. The following review describes the evidence that validates each
      technique as a surrogate marker of atherosclerosis, with an emphasis on
      cardiovascular events and the progression of disease. Both the particular
      strengths and limitations of each imaging modality are discussed.

PMID- 14662106
TI  - Multitasking of the 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor:
      beyond cardiovascular diseases.
AB  - Statins can profoundly affect cellular metabolism by inhibiting 3-hydroxy-3
      methylglutaryl coenzyme A reductase, which is the rate-limiting enzyme
      responsible for cholesterol synthesis. Many physicians prescribe statins to lower
      plasma cholesterol levels, which has beneficial effects in both the primary and
      secondary prevention of coronary artery disease. However, in vitro, in vivo,
      animal, and clinical studies have all shown that statins may also have important
      pleiotropic properties. In fact, a number of clinical studies have suggested that
      statins are involved in modulating diseases such as cancer, osteoporosis, and
      dementia (including Alzheimer's disease). However, because these studies have
      been only preliminary and observational in nature, large randomized, placebo
      controlled studies are needed to confirm the modulatory role of statins in these
      important diseases.

PMID- 14662105
TI  - The cardioprotective effects of statins.
AB  - In addition to their lipid-modulating properties, statins have a large number of
      beneficial cardiovascular effects that have emerged over time and that were not
      anticipated during drug development. The lipid and nonlipid effects act in a
      concerted way to reduce the ischemic burden of the myocardium and to protect it
      against injury. By acting on the vessel wall, statins may prevent lesion
      initiation and repair injuries, enhance myocardial perfusion, slow lesion
      progression, and prevent coronary occlusion. They may also directly reduce
      myocardial damage, favor myocardial repair, and protect against immune injury.
      This review focuses on properties of statins that contribute to their
      cardioprotective effect. The first section includes information on modulation of
      vascular tone, endothelial permeability and function, inhibition of complement
      injury, curbing of foam cell formation, antioxidant and anti-inflammatory
      properties, and profibrinolytic and anticoagulant activities. The second section
      relates to reduction of myocardial necrosis, myocardial hypertrophy, blood
      pressure, and heart failure, as well as mobilization of endothelial progenitor
      cells for repair, angiogenic effects, and immunomodulation. In many instances,
      results of in vitro and animal studies have raised expectations and prompted
      studies in humans. Several clinical trials have confirmed these expectations and
      have strengthened the value of statins as valuable antiatherosclerotic and
      cardioprotective agents.

PMID- 14662107
TI  - Fibrates for treatment of the metabolic syndrome.
AB  - The National Cholesterol Education Program Adult Treatment Panel III has provided
      a clinical definition for the metabolic syndrome that is practical for use in an
      office setting. Identification and treatment of the metabolic syndrome is of
      enormous public health importance because it is associated with a marked
      elevation in coronary heart disease risk and affects nearly 25% of adults in the
      United States. First-line therapy is lifestyle modification, which includes body
      weight reduction, increased physical activity, and moderation of the dietary
      glycemic load. Drug treatments focusing on the major components of the syndrome
      (atherogenic dyslipidemia, hypertension, and a prothrombotic state) have
      demonstrated efficacy for reducing coronary heart disease events. Fibrates seem
      to be particularly effective in patients for whom a disturbance of the
      triglyceride-high-density lipoprotein axis is the primary lipid disorder.
      Fibrates also appear to influence a number of emerging risk factors, including
      hemostatic and inflammatory markers and indicators of improved vascular wall
      biology, which may contribute to their cardioprotective effects.

PMID- 14662108
TI  - Role of selective cholesterol absorption inhibition in the management of
      dyslipidemia.
AB  - Ezetimibe, a cholesterol absorption inhibitor, lowered low-density lipoprotein
      cholesterol levels and improved high-density lipoprotein cholesterol and
      triglyceride levels when used as monotherapy or when coadministered with a statin
      in clinical trials, and its safety profile is similar to placebo or statin plus
      placebo. Addition of ezetimibe to ongoing statin therapy increased the proportion
      of patients reaching recommended low-density lipoprotein cholesterol treatment
      goals. Ezetimibe is an effective treatment option that may enable more patients
      with hypercholesterolemia to achieve optimal cholesterol levels and reduce their
      risk for coronary heart disease.

PMID- 14662109
TI  - Emerging, noninvasive surrogate markers of atherosclerosis.
AB  - Noninvasive surrogate markers of atherosclerosis allow the physician to identify
      subclinical disease before the occurrence of adverse cardiovascular events,
      thereby limiting the need to perform invasive diagnostic procedures. Imaging
      modalities, such as carotid artery ultrasound, two-dimensional echocardiography,
      coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle
      brachial indices, brachial artery reactivity testing, and epicardial coronary
      flow reserve measurements, provide information that may improve the predictive
      value of a person's risk of developing clinically significant atherosclerotic
      disease. Newer imaging modalities have also emerged to bring insight into the
      pathophysiology and treatment of atherosclerosis.

PMID- 14662110
TI  - Biologic therapies for dyslipidemia.
AB  - Biologic therapies involve the utilization of proteins, DNA, antibodies, or other
      substances derived or synthesized from living tissue for therapeutic effects.
      There are several biologic therapies in clinical development for the prevention
      and treatment of atherosclerosis. The most advanced in human trials are
      apolipoprotein mimetics, which include apolipoprotein A-1 Milano and phospholipid
      complexes. Infusions of these apolipoprotein mimetics have been demonstrated to
      reduce atherosclerotic development in both animal models and humans.
      Autoimmunization to create neutralizing antibodies to cholesteryl ester transfer
      protein is also in human trials. Gene therapies to reduce low-density
      lipoproteins and increase high-density lipoproteins are on the horizon, but the
      ability to safely prolong gene expression in humans will require the development
      of novel vectors.

PMID- 14662112
TI  - Consensus interferon versus interferon-alpha 2b plus ribavirin in patients with
      relapsing HCV infection.
AB  - Management of HCV infection and related liver disease with treatment currently
      available lead to a sustained virological response in 20% of patients using
      interferon (IFN)-alpha mono-therapy and approximately 40-45% in those on
      combination therapy with ribavirin.The aim of the present investigation was to
      compare the effect of consensus interferon alphacon-1 (C-IFN), and IFN-alpha 2b
      plus ribavirin, in patients relapsing after treatment with interferon alone. A
      total of 112 randomised patients with relapsing HCV infection (M/F=53/59), were
      treated for 24 weeks with: (A) IFN-alpha 2b starting with 5/6MU/day till
      negativity of HCV-RNA followed by 3MU every other day, plus ribavirin 15mg/kg/day
      (n=34); (B) C-IFN 9microg/day (n=40); (C) ursodeoxycholic acid (UDCA; sodium
      salt) 450mg/day (n=37). At the end of treatment, patients were observed at follow
      up for 24 weeks.Clearance of HCV-RNA was achieved by the end of treatment in 23
      patients (68%) in Group A and 21 also showed a biochemical response with normal
      ALT; in Group B, 33 patients (82%) had both a virological and a biochemical
      response; in Group C, one patient cleared HCV-RNA. At the end of follow-up
      (sustained-response), 29% of patients in Group A (n=10/34) had negative PCR
      (seven patients relapsed at the 4th week, six at the 12th); in Group B, a
      sustained response was achieved in 58% (p<0.03; two patients relapsed at the 4th
      week, three at the 12th and five at the 24th).MAJOR SIDE EFFECTS COMPRISED:
      neutropenia (n=17) and decrease in Hb>1.5g/dl (n=33) in Group A, recurrence of
      psoriasis in two patients in Group B and abdominal discomfort and diarrhoea in 11
      patients in Group C.Rapid clearance of circulating HCV-RNA was induced by C-IFN
      (66% at three weeks, 71% at six weeks): this was a good prognostic index both for
      end of treatment and sustained response. Treatment with C-IFN lead to a higher
      response rate compared to that of recombinant IFN-alpha 2b in association with
      ribavirin. The action of C-IFN is superior in the time taken to reach the maximal
      response rate during treatment and in the lower prevalence of relapse of the
      infection.

PMID- 14662111
TI  - Flavonoids for reduction of atherosclerotic risk.
AB  - Flavonoids are polyphenolic compounds found in fruits, vegetables, and beverages
      derived from plants. Foods thought historically by many societies to have healing
      properties--cocoa, red wine, and tea--are particularly rich in flavonoids. A
      majority of prospective cohort studies demonstrate a significant inverse
      association between flavonoid consumption and cardiovascular risk. Short-term
      studies demonstrate numerous plausible mechanisms by which flavonoids may confer
      cardiovascular protection: they inhibit low-density lipoprotein oxidation, reduce
      thrombosis, improve endothelial function, and reduce inflammation. No long-term,
      randomized, controlled trials of flavonoids with hard clinical endpoints have
      been conducted. Although there are no recommended daily intake goals for
      flavonoids, the data presented provide additional rationale to eat a diet
      containing a variety of flavonoid-rich foods and beverages.

PMID- 14662113
TI  - Long-term changes of peripheral blood CD4-positive T cell subsets (Th1, Th2) in
      chronic hepatitis C patients with a sustained response or no response to IFN.
AB  - BACKGROUND/AIM: The mechanisms that determine the persistence or clearance of
      viral infection in patients with chronic hepatitis C (CHC) are not well known.
      The goal of this study was to clarify changes of the Th1 and Th2 cell subsets of
      peripheral blood CD4-positive T cells (PB-CD4+Tc) in CHC patients after
      successful elimination of HCV. PATIENTS AND METHODS: Eighteen CHC patients
      received natural IFN-alpha at a dose of 5-10MU daily for 2 weeks and three times
      weekly for 22 weeks, and then were followed for 24 weeks after the completion of
      IFN therapy (Week 48). Based on the response to IFN, the subjects were divided
      into two groups: non-responders had detectable serum HCV-RNA at the end of follow
      up (Week 48), while responders did not. Before treatment and in Weeks 2, 24, and
      48, the intracellular cytokines of peripheral CD4+ T cells were detected by flow
      cytometry to separate IFN-gamma+/IL-4- (Th1) cells from IFN-gamma-/IL-4+ (Th2)
      cells. RESULTS: The percentage of Th1 and Th2 cells peaked in Week 2 and then
      decreased to near baseline by Weeks 24 or 48 in both groups. However, a
      statistically significant change in the percentage of Th1 cells was only seen in
      the responders. The baseline percentage of Th1 cells was significantly lower in
      the responders than in the non-responders, while the percentage of Th2 cells at
      baseline, Week 24 and 48 was significantly lower in responders than in non
      responders. CONCLUSIONS: Our results suggest that the baseline Th1 and Th2 cells
      may be related to the IFN response to IFN.

PMID- 14662114
TI  - Pilot study of prolonged interferon-alpha retreatment in chronic hepatitis C
      patients with genotype 1b.
AB  - OBJECTIVES: To investigate the efficacy of prolonged IFN retreatment for 3 years
      in chronic hepatitis C patients with high viral load and IFN treatment-resistant
      genotype 1b. PATIENTS AND METHODS: The study was conducted in 12 patients, not
      HCV RNA-negative after completion of the initial treatment. Retreatment consisted
      of administration of 6 million international units (MIU) of natural interferon
      alpha, two or three times a week for 3 years. RESULTS: One patient was withdrawn
      for personal reasons. All other 11 patients completed treatment without any
      serious adverse reactions and were followed for 3 years. Of the patients, 4 (36%)
      showed a sustained virological response, 5 (45%) showed a biochemical response,
      and 2 (18%) relapsed after retreatment. All patients with a sustained response
      had a transient response to initial therapy. Patients showing a sustained
      response tested negative for HCV RNA within the first 6 months of retreatment.
      CONCLUSIONS: After prolonged IFN retreatment, a significant number of patients
      showed a sustained response for the first time and long-term improvement in ALT
      level.

PMID- 14662115
TI  - Decreased CD3 zeta molecules of T lymphocytes from patients with hepatocellular
      carcinoma associated with hepatitis C virus.
AB  - Most hepatocellular carcinomas (HCC) occur in chronic liver disease. Under such
      conditions, an impaired cellular immune response is often observed, but the
      mechanisms of this deficiency are unclear. The down-modulation of CD3 zeta (a key
      molecule in signal-transducing factor of T cell receptor) leads to a reduction in
      the function of T cells. In this study, we demonstrated the decreased expression
      of CD3 zeta on T cells from hepatitis C virus (HCV) infected hosts and HCC
      patients and clarified the correlation between the expression of CD3 zeta and
      tumor progression. Flowcytometrical analysis of CD3 zeta on peripheral T
      lymphocytes from 12 HCV infected hosts and 36 HCC bearing patients showed a
      significantly lower CD3 zeta expression than normal controls. Compared with tumor
      infiltrating T lymphocytes (TIL), intrahepatic T lymphocytes (IHL) and peripheral
      T lymphocytes (PBL) from 11 HCC bearing patients, the expression of CD3 zeta on
      TIL was significantly lower than PBL, and the expression level of CD3 zeta on IHL
      was almost equal to that on TIL. These results suggest that the down-modulation
      of CD3 zeta of T lymphocytes in HCV infected hosts may be one of the reasons why
      multicentric occurrence and intrahepatic metastasis occur more frequently in HCC
      patients than another malignancies.

PMID- 14662116
TI  - Studies on the correlation among the fucosylation index, concentration of alpha
      fetoprotein and des-gamma-carboxy prothrombin as prognostic indicators in
      hepatocellular carcinoma.
AB  - Our previous results showed that the fucosylation index (FI) was considered to be
      a useful prognostic factor in patients with hepatocellular carcinoma (HCC). On
      the other hand, serum concentrations of alpha-fetoprotein (AFP) and des-gamma
      carboxy prothrombin (DCP) were regarded as prognostic indicators. However, the
      relationship among FI, AFP, and DCP as prognostic factors remained unknown. The
      aim of this study was to elucidate the correlation among these three prognostic
      factors. One hundred and seventy-six patients with HCC from 1990 to 1998, who
      showed increment of serum AFP concentrations more than 30ng/ml before treatment,
      were examined in the present study. FI was determined in these patients by
      crossed immunoaffino-electrophoresis in the presence of Lens culinaris
      agglutinin. FI of AFP was defined as the percentage of the L. culinaris
      agglutinin (LCA)-reactive species in total AFP (same as L3 fraction). Serum
      concentrations of DCP were also measured. Enrolled patients with HCC underwent
      transcatheter arterial embolization, chemoembolization, percutaneous ethanol
      injection, and/or percutaneous microwave coagulation therapy. The current
      patients status was the one which was confirmed at the end of March 2001.
      Analysis by the Cox's proportional hazards model showed that FI, AFP, and DCP
      were significant prognostic factors. When the tentative demarcation levels of FI,
      AFP, and DCP were set at 18%, 200ng/ml, and 0.06arbitrary units (AU)/ml,
      respectively, the following results for the prognostication of patients with HCC
      were obtained. First, the survival rates in the groups with one out of the three
      optional markers over the demarcation level were significantly lower than the
      survival rates of other groups, whose optional one marker was equal to or less
      than the demarcation level, respectively. Next, the survival rates in the groups
      in which two out of three optional markers were over the demarcation levels were
      lower than the survival rates of other groups, whose optional two markers were
      equal to or less than the demarcation levels, with high significance. On the
      contrary, there was absence or attenuation of statistically significant
      differences in the survival rates between the groups in which two of the three
      optional markers showed no accordant results (high FI and low AFP versus low FI
      and high AFP, low FI and high DCP versus high FI and low DCP, high DCP and low
      AFP versus low DCP and high AFP). Finally, we compared the survival rates between
      the HCC groups, whose optional one marker was over the demarcation level and
      whose remainders were equal to or less than the demarcation levels and another
      HCC group whose optional one marker was equal to or less than the demarcation
      level and whose remainders were over the demarcation levels to reconfirm the
      weight of each prognostic factor. These comparisons together with Cox's analysis
      showed that the weight of each prognostic factor in the survival rates is
      consecutively ordered as DCP, FI, and AFP. The present study indicates that
      measurements of FI, AFP, and DCP from the sera before the initial treatment
      improve prognostic estimates and appraisal of the therapeutic outcome in patients
      with HCC.

PMID- 14662117
TI  - Induction of multiple matrix metalloproteinase genes in human hepatocellular
      carcinoma by hepatocyte growth factor via a transcription factor Ets-1.
AB  - Matrix metalloproteinases (MMPs) have been implicated in progression of
      hepatocellular carcinoma (HCC), as have hepatocyte growth factor (HGF) and its c
      Met receptor. We investigated regulation of MMP gene expression by HGF in human
      HCC. Expression of mRNAs encoding MMPs, HGF and c-Met receptor was examined by
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) in human
      HCC and in five human HCC cell lines. HCC cells were treated with HGF, and mRNA
      expression for MMPs and Ets-1 which activates transcription of MMPs was
      investigated. Ets binding activity was determined by gel mobility shift assay.
      MMP promoter activities were evaluated by reporter gene assay. Effects of Ets-1
      antisense oligonucleotides were also examined. At the mRNA level, MMP-1, -3, -7
      as well as c-Met were overexpressed in HCC compared with corresponding
      nonneoplastic liver tissues, although MMP-2, -9 or HGF were not. HGF dose
      dependently induced Ets-1 together with an increased Ets binding activity,
      followed by transcription of MMP-1, -3, and -7. HGF increased MMP promoter
      activity, as did cotransfection with Ets-1. Ets-1 antisense oligonucleotide
      transfection down-regulated the MMP expression, and abolished induction by HGF.
      In conclusion, certain MMPs and c-Met, overexpressed in HCC cells, are induced by
      HGF via Ets-1. This pathway may contribute to tumor progression.

PMID- 14662118
TI  - Zonal differences in effects of HGF/SF and EGF on DNA synthesis in hepatocytes at
      different times post-hepatectomy.
AB  - This study was done for investigation of the DNA synthesis induced by HGF/SF and
      EGF in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) isolated at
      different times post-hepatectomy. Preparation, culture, and DNA synthesis of PPH
      and PVH were done as previously described. In both PPH and PVH isolated at 6 and
      12h post-hepatectomy, the maximum DNA synthesis induced by both HGF/SF and EGF
      was observed from 24 to 48h post-hepatectomy. In contrast, in both types of
      hepatocytes isolated at 36, 72 and 96h, 1 and 2 weeks, and 1 month post
      hepatectomy, maximum DNA synthesis was observed from 48 to 72h. However, maximum
      DNA synthesis induced by HGF/SF and EGF was at its lowest in PPH isolated at 12h
      and PVH isolated at 6h post-hepatectomy. Maximum DNA synthesis returned to the
      control level in PPH and PVH isolated at 72 and 96h post-hepatectomy,
      respectively. Specific binding studies using [125I] HGF/SF and [125I] EGF
      supported the above data. From these data, it was demonstrated that first, the
      PPH and PVH cell cycles have the same post-hepatectomy, but are dependent on the
      preparation time. Secondly, differences in DNA synthesis in PPH and PVH post
      hepatectomy suggest that liver regeneration may occur unevenly.

PMID- 14662119
TI  - Possible contribution of circulating interleukin-10 (IL-10) to anti-tumor
      immunity and prognosis in patients with unresectable hepatocellular carcinoma.
AB  - OBJECTIVES: Interleukin-10 (IL-10) has been implicated in immune deficiency in
      patients with cancer. The relationship of this cytokine as measured in serum to
      anti-tumor immunity and prognosis was investigated in unresectable hepatocellular
      carcinoma. METHODS: This study consisted of 74 consecutive patients with
      unresectable hepatocellular carcinoma (median age, 65 years). Forty-four healthy
      age-matched subjects and 32 patients with cirrhosis but no carcinoma served as
      controls. Patients with hepatocellular carcinoma were divided into those with
      serum IL-10 concentrations above (high group, n=39) or below (low group, n=35)
      10pg/ml. RESULTS: Age, gender, Child-Pugh grade, and tumor stage distributions
      were similar in high and low groups. The patients of high group showed lower in
      lymphokine-activated killer (LAK) and natural killer (NK) activities than those
      of low group (P<0.01 and 0.01, respectively). Serum IL-10 concentration was a
      significant factor contributing to low activities of LAK and NK by logistic
      regression analysis (P<0.05 and 0.05, respectively). The high group had a
      significantly shorter survival (median, 3 months) than low group (median, 12
      months; P<0.02, generalized Wilcoxon test). CONCLUSIONS: These data suggest that
      serum IL-10 concentration is a possible factor contributing to poor prognosis and
      low anti-tumor immunity in patients with unresectable hepatocellular carcinoma.

PMID- 14662120
TI  - Comparison of contrast-enhanced harmonic ultrasonography and power Doppler
      ultrasonography for depicting vascularity of hepatocellular carcinoma identified
      by angiography-assisted CT.
AB  - The sensitivity of contrast-enhanced harmonic gray scale imaging was compared
      with that of power Doppler sonography in depicting tumor vascularity and contrast
      enhancement of hepatocellular carcinoma (HCC) identified by angiography-assisted
      computed tomography (CT). One hundred thirty-nine classic HCC nodules (108
      patients), each appearing as a high-attenuation mass on early-phase CT during
      hepatic arteriography and as a perfusion defect on CT during arterial
      portography, were evaluated. Vascular findings and contrast enhancement patterns
      were evaluated by contrast-enhanced harmonic gray scale imaging. Arterial
      pulsatile flow into each nodule was checked by power Doppler sonography.
      Sensitivity of each modality for depicting tumor vascularity was examined by
      angiography-assisted CT findings as the gold standard. The sensitivity of
      contrast-enhanced harmonic gray scale imaging (134/139, 96.4%) was significantly
      greater than that of power Doppler sonography (96/139, 69.1%) (P<0.05). Twenty
      six of twenty-seven nodules (96.3%) in the lateral segment, in which motion
      artifact is likely, were enhanced by contrast-enhanced harmonic gray scale
      imaging. Contrast-enhanced harmonic gray scale imaging is more sensitive than
      power Doppler sonography and is a noninvasive method that can be used as
      effectively as angiography-assisted CT to evaluate tumor vessels and contrast
      enhancement of HCC.

PMID- 14662121
TI  - Novel mutations identified in the human multidrug resistance-associated protein 2
      (MRP2/ABCC2) gene in a Japanese patient with Dubin-Johnson syndrome.
AB  - A 39-year-old Japanese women who has been jaundiced since childhood and
      indicative of Dubin-Johnson syndrome (DJS) underwent MRP2/ABCC2 mutation
      analysis. The results of the analysis revealed two novel mutations, C298T and
      C3928T, and two single nucleotide polymorphisms (SNPs), C3972T and C-24T. One of
      the two mutations (C298T) is in the transmembrane domain. The other mutation
      (C3928T) and the SNP (C3972T) are in the cytoplasmaic domain which are
      concentrated in the second adenosine triphosphate (ATP)-binding cassette. Both of
      the mutations, C298T and C3928T, are immature stop codons. C298T, C-24T and
      C3972T (originating from the mother) and C3928T (from the father) were observed
      to be heterozygous in this patient. Light-microscopy examination of the liver
      biopsy specimens revealed the accumulation of dark pigment granules in most of
      the hepatocytes. In the immunohistochemistry using pAb recognizing the C-terminal
      of the human MRP2, no staining of MRP2 in the canalicular membrane domain was
      observed in the liver sections from this patient. In this patient, the mutations
      with immature stop codons presumably resulted in instability of MRP2 mRNA and/or
      defective synthesis of the truncated protein, which may underlie the loss of the
      expression of functional MRP2 protein.

PMID- 14662122
TI  - Factors affecting plasma progesterone concentration and the retrospective
      determination of time of ovulation in cyclic mares.
AB  - Factors influencing plasma progesterone concentration were investigated in seven
      mares. Two-phase logistic curves were fitted (r=0.98) to plasma progesterone
      concentrations of blood samples collected once daily. In addition to the effect
      of time (P<0.001), there were differences (P<0.01) among mares in the peak height
      of the progesterone plateau and in the (area under the curve) AUC. Plasma
      progesterone concentrations were higher (P<0.001) after a multiple versus single
      ovulation. There was an effect of season (P<0.001), but no significant effect of
      luteal morphology. The retrospective determination of time of ovulation was
      carried out using a linear model on the seven mares and 25 additional mares.
      Linear regression on the measured values or on the ratio to the average
      concentration from D5 to D10, was calculated with the day of cycle between D0 and
      D4. The ovulation date was then calculated using both of these equations, whether
      blood sampling was performed twice or thrice weekly on 25 postpartum mares. The
      accuracy to predict day of ovulation (+/- 1 day) ranged from 88 to 97%. In
      conclusion, the retrospective estimation of time of ovulation in mares was
      possible, although the technique had some limitations.

PMID- 14662123
TI  - Effects of exposure of epididymal boar spermatozoa to seminal plasma on the
      binding of zona pellucida proteins during in vitro capacitation.
AB  - The purpose of the investigation was to determine whether seminal plasma plays a
      role in the increase during in vitro capacitation of the number of boar
      spermatozoa with enhanced binding of zona pellucida proteins. Ejaculated
      spermatozoa and spermatozoa collected from the caudae epididymides of boars were
      incubated at 39 degrees C in a Tyrode's IVF medium. During incubation, the zona
      binding ability of individual spermatozoa was assessed with fluorescein
      conjugated solubilized zona pellucida proteins (FITC-sZP), using a flow
      cytometer. Propidium iodide (PI) was included to simultaneously monitor cell
      viability. During incubation of ejaculated spermatozoa, a percentage of the
      spermatozoa expressed enhanced binding of FITC-sZP. The percentage of viable
      spermatozoa with enhanced binding reached a maximum of 37% (S.D.=8, averaged over
      five boars) after 2-3 h. In epididymal sperm, a similar maximum was observed
      after incubation in vitro, but a longer time of incubation was needed (6 h).
      Also, the rate of cell death of epididymal sperm was much lower than that of
      ejaculated sperm. When epididymal spermatozoa was exposed to seminal plasma in
      vitro, the time needed to reach a maximal percentage of viable spermatozoa with
      enhanced FITC-sZP binding was similar to that in ejaculated semen. However, the
      rate of cell death was still much lower than in ejaculated sperm. We concluded
      that the binding sites on the sperm surface that are involved in the increased
      binding of zona proteins during incubation under IVF conditions were not derived
      from the seminal plasma. The cellular processes leading to the increased binding
      capacity were accelerated by exposure of the sperm to seminal plasma.

PMID- 14662124
TI  - Capacity of boar spermatozoa to bind zona pellucida proteins in vitro in relation
      to fertilization rates in vivo.
AB  - The purpose of this study was to determine variation among boars in the
      percentage of sperm in an ejaculate that express enhanced binding of zona
      pellucida proteins during treatment for capacitation in vitro, and to determine
      whether this relates to fertilizing ability in vivo. Ejaculates (n=35) were
      collected from 12 boars. A sample of each ejaculate was treated for capacitation
      in vitro. During incubation, the zona binding ability of spermatozoa was assessed
      at regular intervals with fluorescein-conjugated solubilized zona pellucida
      proteins (FITC-sZP) and propidium iodide, using a flow cytometer. After
      incubation, a percentage of the sperm had enhanced FITC-sZP binding. The
      percentage of viable sperm with enhanced FITC-sZP binding, expressed as a
      percentage of the total sperm population, increased rapidly over the first 60 min
      and thereafter reached a plateau after 120-180 min. Averaged over all ejaculates,
      the percentage at 180 min was 46% (range 27-61%); this percentage was
      significantly different among boars. However, the variation between ejaculates
      within a boar was relatively small. There was no significant boar effect on the
      rate at which the percentage of viable cells with enhanced FITC-sZP binding
      reached the maximum. In ejaculates (n=14) from four boars (selected from the
      group of 12), we investigated the increase in the percentage of viable sperm with
      enhanced sZP binding during treatment for capacitation in vitro in relation to
      the ability to fertilize in vivo. Sows (n=44) were inseminated 4 h after
      ovulation with a suboptimal insemination dose (0.5x10(9) spermatozoa). Time of
      ovulation was determined using transrectal ultrasonography and sows were killed
      at 120 h after ovulation. The percentage of fertilized oocytes, embryo
      development, and numbers of accessory spermatozoa were determined. The percentage
      of spermatozoa that were viable and showed enhanced sZP binding after 180 min of
      incubation was 48 +/- 12% (range 28-56%). The percentage of fertilized oocytes
      was 85 +/- 27% and 64% of the sows had 100% fertilized oocytes. The percentage of
      sows with 100% fertilized oocytes correlated well (P< or =0.05, R2=0.98) with the
      percentage of viable spermatozoa with enhanced FITC-sZP binding after
      capacitation in vitro.

PMID- 14662125
TI  - Resynchrony of postpartum dairy cows previously treated for anestrus.
AB  - Cows that are diagnosed as anestrus (defined as >3 weeks postpartum, not detected
      in estrus by 1 week before commencement of seasonal breeding and without a
      palpable corpus luteum) have a lower probability of being inseminated, a lower
      conception rate to insemination and hence a lower probability of pregnancy within
      the breeding period. A current progesterone (P) and estradiol benzoate (EB)
      treatment for anestrus results in an 85% insemination rate, but only 57% of cows
      not conceiving to that first insemination are subsequently detected in estrus 14
      28 days later. Resynchrony after an initial anestrous treatment has been used to
      increase the probability that cows not conceiving to first insemination will
      subsequently be detected in estrus. Anestrous cows (n=971) were initially treated
      with an intravaginal P-releasing device for 6 days and given 1 mg EB 1 day after
      device removal (day of EB treatment=Day 0). Cows detected in estrus between Days
      0 and 3 were assigned randomly to be treated with reinsertion of a used P
      releasing device for 8 days (commencing on Day 15), with 0.5 mg EB at reinsertion
      and again 1 day after removal (EB-RS), treatment as for EB-RS group but with
      substitution of 250 microg GnRH for EB at device reinsertion (GnRH-RS), or left
      as untreated controls (no-RS). Resynchrony treatments increased the proportion of
      non-pregnant cows detected in estrus from Days 14 to 28 compared to no-RS (79.1,
      69.8, and 55.1% for EB-RS, GnRH-RS, and no-RS, respectively; P<0.05). Fewer cows
      were pregnant by Days 28 and 56 following GnRH-RS than EB-RS and no-RS. The final
      pregnancy rate was higher following EB-RS treatment than no-RS or GnRH-RS
      treatment (95.0, 88.3, and 88.6%; P<0.05). In conclusion, EB-RS enhanced
      reproductive performance of anestrous cows compared to no-RS.

PMID- 14662126
TI  - Two-dimensional polyacrylamide gel electrophoresis of bovine seminal plasma
      proteins and their relation with semen freezability.
AB  - The objective of this study was to evaluate the low weight (10-30 kDa) protein
      profile of bovine seminal plasma using two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and to determine if any of these proteins was
      associated with semen freezability. Seminal plasma was collected from 16 bulls of
      high or low semen freezability. Twelve protein spots were identified from the 2D
      gel (15%); six of these were present in all samples. Of the 12 proteins found,
      three spots, present in all samples, 3 (15-16 kDa), 5 (16-17 kDa), and 7 (10-12
      kDa) had nonsignificant variation among bulls, regardless of their freezability
      classification. Four proteins were more abundant (P<0.05) in seminal plasma
      samples collected from bulls with high semen freezability than in samples of
      bulls with low semen freezability: the spots 3 (15-16 kDa, pI 4.7-5.2), 7 (11-12
      kDa, pI 4.8-4.9), 11 (13-14 kDa, pI 4.0-4.5), and 23 (20-22 kDa, pI 4.8-5.2). On
      the other hand, spot 25 (25-26 kDa, pI 6.0-6.5) was more abundant (P<0.05) on
      seminal plasma samples from bulls with low semen freezability. The N-terminus
      sequence of protein 7 was identical to the acidic seminal fluid protein (aSFP).
      Protein 23 (after trypsin digestion) had structural similarity to bovine
      clusterin. We concluded that there were differences in the seminal plasma protein
      profile from bulls with low and high semen freezability; aSFP, clusterin,
      proteins 3 and 11 may be used as semen freezability markers; and protein 25 was
      related to low semen freezability.

PMID- 14662127
TI  - Successful vitrification of pronuclear-stage rabbit zygotes by minimum volume
      cooling procedure.
AB  - Rabbit zygotes at the pronuclear-stage were cryopreserved by vitrification using
      a gel-loading tip (GL-tip), Cryoloop or Cryotop. In GL-tip and Cryoloop methods,
      zygotes were first exposed to 10% ethylene glycol (EG)+10% DMSO in TCM199+20%
      fetal bovine serum (FBS) for 2 min, and then equilibrated for 30 s in a
      vitrification solution composed of 20% EG+20% DMSO+0.6 M sucrose in TCM199+20%
      FBS. In Cryotop method, zygotes were first exposed to 7.5% EG+7.5% DMSO+20% FBS
      in TCM199 for 3 min, and then equilibrated for 1 min in a vitrification solution
      composed of 15% EG+15% DMSO+0.5 M sucrose+20% FBS in TCM199. In vitro culture of
      vitrified-warmed zygotes using GL-tip and Cryoloop resulted in low cleavage rates
      (2 and 5%, respectively) and no development into blastocysts. In contrast,
      zygotes vitrified-warmed using Cryotop exhibited higher proportions of cleavage
      (58%) and development into blastocysts (24%). When compacted morulae or early
      blastocysts were vitrified by these three procedures, 80-93% of them exhibited
      blastocoele expansion or zona hatching during the subsequent 48 h of culture. Use
      of Cryotop instead of GL-tip or Cryoloop for zygote vitrification, without
      changing conditions of solutions and periods for exposure, equilibration and post
      warm dilution, resulted in cleavage and blastocyst development rates of 88 and
      45%, respectively. A longer exposure time (10 min) of zygotes to 7.5% EG+7.5%
      DMSO+20% FBS in TCM199 resulted in higher proportions of zygotes cleaving (94%)
      and developing into blastocysts (51%) after Cryotop vitrification. Proportions of
      post-warm zygotes (10-min exposure group) and fresh control zygotes developing
      into newborn offspring were 36 and 53%, respectively. Pronuclear-stage rabbit
      zygotes were successfully cryopreserved by vitrification using the Cryotop
      method.

PMID- 14662128
TI  - Xenotransplantation: a tool for reproductive biology and animal conservation?
AB  - The transplantation of reproductive organs, including ovaries and ovarian tissue,
      was pioneered over 100 years ago. In the 1960s, ovarian grafting was used as a
      tool to investigate ovarian function, but with the recent development of more
      effective cryopreservation protocols for ovarian tissue, germline preservation
      and propagation have now become realistic goals. This review describes progress
      in ovarian banking and ovarian tissue transplantation, with emphasis on how fresh
      and frozen ovarian tissue can be used in assisted reproduction for both humans
      and animals. This paper focuses most closely on the potential value of
      xenotransplantation, the transplantation of gonads from one species to another,
      to conserve rare and endangered species. Specific attention is drawn to the use
      of xenotransplantation as a strategy for generating viable gametes that can be
      used to produce live fertile offspring. Other upcoming xenogeneic technologies
      that may be of potential significance in animal conservation, such as
      transplantation of whole ovaries or isolated growing follicles, and even male
      germ cells, are discussed.

PMID- 14662129
TI  - Immunocytochemical localization of cytochrome P450 aromatase in the testis of
      prepubertal, pubertal, and postpubertal horses.
AB  - The large amount of testicular estrogens produced by the stallion is unique
      compared to the amounts found in other domestic species. Although the cellular
      locale of the cytochrome P450 aromatase (P450arom) enzyme that converts C19
      androgens to C18 estrogens has been identified in the Leydig cell of adult equine
      testis, the location in the immature equine testis is not known. The goal of this
      work was to localize the enzyme in colts and stallions during sexual development.
      Testes were obtained from prepubertal (n=7), pubertal (n=6), and postpubertal
      (n=8) colts and stallions during both the breeding and non-breeding seasons.
      Tissue was fixed and prepared for immunocytochemistry (ICC), carried out with an
      antiserum against human placental P450arom. In prepubertal colts, there was
      distinct immunopositive staining of a similar degree within both the Leydig cell
      and the seminiferous tubule. Horses in the pubertal group had strong Leydig cell
      immunopositive staining and a slight degree of positive staining within the
      seminiferous tubules. Postpubertal stallions exhibited definitive immunopositive
      staining within Leydig cells but not within the seminiferous tubules. Therefore,
      P450arom is present within the Leydig cell throughout sexual development. In
      contrast, the presence of P450arom within the seminiferous tubule based upon ICC
      appeared to be gone by adulthood, suggesting that an age-dependent shift in the
      locale of this enzyme as the stallion matures.

PMID- 14662130
TI  - The effect of acetylsalicylic acid and captopril on uterine and ovarian blood
      flow during the estrous cycle in mares.
AB  - In previous studies, transrectal color Doppler sonography was used to demonstrate
      an increase in genital blood flow resistance in subfertile mares. The objectives
      of the present study were to determine the effects of an anticoagulant
      (acetylsalicylic acid) and a vasodilator (captopril) on uterine and ovarian
      perfusion and plasma progesterone concentrations in cycling mares. From Day 1 to
      11 of an estrous cycle (Day 0=day of ovulation following prostaglandin-induced
      luteolysis), five Trotter mares were given 2500 mg lactose, 2500 mg ASA, or 50 mg
      captopril twice daily in their feed (one compound per cycle, in random order).
      Transrectal color Doppler sonography was used to examine both uterine arteries
      and the ovarian artery ipsilateral to the corpus luteum once daily, immediately
      prior to administration of the drug. Blood flow resistance was determined
      semiquantitatively using the pulsatility index (PI) and plasma progesterone
      concentrations were determined with an enzyme immunoassay. Compared to the
      placebo, both ASA and captopril decreased mean PI values of both uterine arteries
      of all mares. On average, ASA decreased the PI of the uterine arteries by 25%;
      this was more (P<0.05) than the average decrease (13%) caused by captopril. Both
      drugs decreased (P<0.05) blood flow resistance in the ovarian arteries, although
      there was no difference (P<0.05) in their efficacy. In addition, both ASA and
      captopril increased (P<0.0001) plasma progesterone concentrations (18 and 17%,
      respectively). In conclusion, either ASA or captopril improved uterine and
      ovarian perfusion; however the effects on fertility were not determined.

PMID- 14662131
TI  - Ultrasound and endocrine evaluation of the ovarian response to a single dose of
      500 IU of eCG following a 12-day treatment with progestogen-releasing
      intravaginal sponges in the breeding and nonbreeding seasons in ewes.
AB  - A standard dose of 500 IU of eCG is commonly given to progestogen pre-treated
      anestrous ewes for induction of estrus. Twelve seasonally anestrous and 12 cyclic
      Western White Face ewes were treated for 12 days with intravaginal sponges
      impregnated with medroxyprogesterone acetate (MAP). In trials in both the
      breeding and nonbreeding seasons, six randomly selected ewes were given 500 IU of
      eCG at sponge removal to determine the effects of low dose of eCG on ovarian
      antral follicular dynamics and ovulation. Ultrasound scanning and blood sampling
      were done daily. Treatment with eCG did not have marked effects on antral
      follicular growth. All ewes ovulated, except for five of six control anestrous
      ewes. Luteal structures and progesterone secretion were confirmed in all but the
      control anestrous ewes. In the breeding season, peak progesterone concentrations
      were greater (P<0.05) in eCG-treated compared to control ewes. Daily serum
      estradiol concentrations were greater in the periovulatory period in eCG-treated
      compared to control ewes (treatment-by-day interaction; P<0.05), particularly in
      anestrus. Progestogen-treated ewes ovulated follicles from several follicular
      waves, in contrast to ovulations of follicles from the final wave of the cycle in
      untreated, cyclic ewes. Anestrous ewes exhibited more frequent follicular waves
      and FSH peaks compared to cyclic ewes after a progestogen/eCG treatment. In
      conclusion, 500 IU of eCG given after 12 days of progestogen treatment had
      limited effects on the dynamics of ovarian follicular waves. However, eCG
      treatment increased serum concentrations of estradiol during the periovulatory
      period, particularly in anestrous ewes; this probably resulted in the synchronous
      estrus and ovulation in anestrous ewes.

PMID- 14662132
TI  - Developmental competence of bovine oocytes: effects of follicle size and the
      phase of follicular wave on in vitro embryo production.
AB  - Developmental competence of bovine oocytes collected from follicles of different
      size categories (in either the growth or the dominant phase of the first
      follicular wave) was studied, with the aim of improving in vitro embryo
      production. Estrus and ovulation of 39 cyclic Holstein dairy cows were
      synchronized by two prostaglandin F2alpha treatments at 11-day intervals and one
      hCG treatment on the day of onset of estrus (Day 0). Cows with follicles in
      either the growth (Day 3, n=25) or the dominant phase (Day 7, n=14) were
      slaughtered, and follicles >5 mm were counted. Three oocyte populations were
      recovered separately from large (11-15 mm), medium (6-10 mm) and small (2-5 mm)
      follicles in both follicular phases. All collected cumulus-oocyte complexes
      (COC), except for markedly atretic oocytes without cumulus cells, were used in
      experiments. Oocytes were matured, fertilized and cultured by standard methods.
      There were no significant differences between the growth and the dominant phases
      for mean numbers of large follicles, usable oocytes and embryos per donor.
      Generally, those numbers were low, but the development rates of oocytes into
      blastocysts were high, particularly in the growth phase (60.0%). Mean (+/-
      S.E.M.) numbers of medium follicles, oocytes and embryos per donor were higher in
      the growth as compared with the dominant phase; in the usable oocytes and
      embryos, this difference was significant (9.6 +/- 1.4 and 3.5 +/- 0.6 versus 3.9
      +/- 0.6 and 1.1 +/- 0.3; P<0.01). The development rates of oocytes into
      blastocysts, however, did not differ significantly between the growth and the
      dominant phases (36.7% versus 27.8%). Mean numbers of usable oocytes and embryos
      per donor recovered from small follicles in both follicular wave phases were
      similar. The development rate of oocytes into blastocysts was generally low, but
      higher (P<0.01) in the growth than in the dominant phase (24.5% versus 11.7%).
      Comparison between the two phases showed that mean number of all counted
      follicles and all usable oocytes collected per donor were similar, but the mean
      number of embryos per donor and the development rate of oocytes into blastocysts
      were higher in the growth phase than in the dominant phase (8.0 +/- 1.2 versus
      3.8 +/- 2.4; P=0.012 and 30.3% versus 14.9%; P<0.01). The interaction between
      follicle size and the phase of follicular wave affected the efficiency of embryo
      production. The yield of embryos was primarily influenced by the number of
      oocytes collected from medium follicles and the developmental competence of
      oocytes from small follicles. The growth phase was more effective for oocyte
      collection; the number of oocytes from medium follicles and the developmental
      competence of oocytes from small follicles decreased in the dominant phase.

PMID- 14662133
TI  - Involvement of the plasminogen activation system in cow endometritis.
AB  - The objectives of this study were to investigate the: (a) presence and activity
      of components of the "plasminogen activators/plasmin" system in dairy cows with
      or without endometritis; (b) variations in enzyme activity according to the
      degree of endometritis; and (c) associations between these enzymes and changes in
      endometrial histology after intrauterine antibiotic treatment. Endometrial
      biopsies were collected from anestrus (no palpable ovarian structures and milk
      progesterone <1 ng/ml) Holstein cows, 30-40 days postpartum. On the basis of a
      vaginoscopic examination, rectal palpation of the cervix and uterus, and
      endometrial histology, there were 92 cows with endometritis and 20 cows without
      endometritis. After biopsy collection, each cow was given an intrauterine
      infusion of 1.5x10(6) IU of procaine penicillin G. In cows with endometritis,
      genital tract examinations and biopsies were repeated 2 weeks later. Both
      plasminogen activators (PAs), tissue type (t-PA) and urokinase (u-PA), were
      immunologically identified in all uterine biopsies. Plasminogen activator
      activity (PAA) increased, whereas plasminogen activator inhibition (PAI) and
      plasmin inhibition (PI) decreased in proportion to the degree of inflammation.
      Two weeks after intrauterine treatment, PAA had decreased significantly in all
      cows that had reduced severity of endometrial inflammation and had increased
      significantly in all cows with increased severity of inflammation. The change in
      the degree of inflammation depended upon plasminogen activator activity; cows
      with higher PAA were more likely to improve. In conclusion, there was evidence
      for a role of the plasminogen activation proteolytic system in bovine
      endometritis.

PMID- 14662134
TI  - Motility and penetration competence of frozen-thawed miniature pig spermatozoa
      are substantially altered by exposure to seminal plasma before freezing.
AB  - The objective was to determine if exposure of spermatozoa to seminal plasma
      before freezing decreases its freezability, assessed by percentage motile cells
      (using computer-assisted semen analysis) and in vitro penetration ability (using
      in vitro fertilization and chlortetracycline fluorescence assessment). Ejaculated
      spermatozoa from miniature pigs were washed by centrifugation within 20 min after
      collection, then incubated in seminal plasma or modified Hulsenberg VIII diluents
      (mHM). When the spermatozoa were cryopreserved, spermatozoa incubated in seminal
      plasma before freezing had significantly lower post-thaw motility than
      spermatozoa incubated in mHM. The incubation of spermatozoa in seminal plasma
      also significantly prevented frozen-thawed spermatozoa from penetrating the
      oocytes. The second experiment, using unfrozen spermatozoa, was to determine if
      the incubation of spermatozoa with seminal plasma reduced penetration ability
      before freezing, resulting in a significantly lower penetration rate after
      freezing (compared with spermatozoa incubated without seminal plasma). The
      penetration competence of unfrozen spermatozoa was significantly decreased by
      incubation in seminal plasma, but no difference in motility was observed between
      spermatozoa exposed to seminal plasma versus mHM. We concluded that ejaculated
      seminal plasma contained some factor(s) that modified the sperm before freezing
      and reduced the freezability and post-thaw penetration competence of spermatozoa.

PMID- 14662135
TI  - Separation of canine epididymal spermatozoa by Percoll gradient centrifugation.
AB  - The objective was to characterize the separation of canine epididymal spermatozoa
      on a Percoll gradient. Epididymal spermatozoa were overlaid on a 45 and 90%
      discontinuous Percoll gradient and centrifuged at 700 x g for 20 min. The Percoll
      column was separated into six fractions (top to bottom, A-F) after
      centrifugation. Fractions A-C contained few spermatozoa. Spermatozoa with bent or
      folded tails and a large amount of granular debris were observed in Fraction B.
      Fraction D contained many nonmotile spermatozoa, erythrocytes and round
      epithelial cells. Spermatozoa in Fraction E had significantly lower motility than
      those in the initial layer. Spermatozoa in Fraction F had motility similar to
      those before separation. Fraction F contained 40.6% of the motile spermatozoa
      layered and 67.5% of all motile spermatozoa recovered. There was no significant
      difference between Fraction F and the initial layer in sperm membrane integrity.
      In the sperm-oocyte penetration assay, spermatozoa from Fraction F had a
      significantly higher penetration rate into the immature homologous oocytes than
      those from Fraction E. Although the recovery rate of the motile spermatozoa was
      low, the canine epididymal spermatozoa with motility, membrane integrity and
      penetrating capability could be separated by two-layer discontinuous Percoll
      gradient centrifugation.

PMID- 14662136
TI  - In vitro maturation, fertilization and early cleavage rates of bovine fetal
      oocytes.
AB  - The in vitro developmental competence of oocytes harvested from 3 to 6 mm
      follicles from ovaries of 7.5 months to term fetuses and adult cows was compared.
      Cumulus oocyte complexes (COCs) were washed and placed in 200 microl droplets of
      maturation medium 199, supplemented with 10 microg/ml FSH, 10 microg/ml LH, 1.5
      microg/ml estradiol, 75 microg/ml streptomycin, 100 IU/ml penicillin, 10 mM
      Hepes, and 10% fetal bovine serum (FBS) under oil and incubated for 24 h at 39
      degrees C and 5% CO2. Matured oocytes were exposed to frozen-thawed TALP swim-up,
      heparin-capacitated sperm (20 h, 39 degrees C, 5% CO2). Presumptive zygotes were
      cultured in medium 199 containing 8 mg/ml BSA-V, 100 IU/ml penicillin G, 75
      microg/ml streptomycin, and 10 mM Hepes (48 h, 39 degrees C, 5% CO2).
      Oocytes/embryos were fixed, stained with DAPI, and evaluated under fluorescent
      microscopy to assess maturation, fertilization, and subsequent embryonic
      development. There was a difference (P<0.05) between fetal and adult cow oocytes
      for in vitro maturation (IVM; 80.1% versus 92.0%), fertilization (69.3% versus
      79.9%), and cleavage rates (36.7% versus 49.9%), respectively. Poor IVM,
      fertilization and embryonic development of fetal oocytes may be due to a higher
      incidence of blockage at germinal vesicle (GV) and metaphase-I (M-I) stage after
      IVM (12.0% versus 2.3% for fetal versus adult oocytes, respectively, P<0.05).
      Although the IVF results with fetal oocytes are poorer than with adult cow
      oocytes, they were still high enough to be considered for use in research and
      when death of the dam and/or fetus is pre-mature or sudden.

PMID- 14662137
TI  - Xenogenous fertilization of equine oocytes following recovery from slaughterhouse
      ovaries and in vitro maturation.
AB  - The in vitro production (IVP) of equine embryos using currently available
      protocols has met limited success; therefore investigations into alternative
      approaches to IVP are justified. The objective of this study was to evaluate the
      feasibility of xenogenous fertilization and early embryo development of in vitro
      matured (IVM) equine oocytes. Follicular aspirations followed by slicing of
      ovarian tissue were performed on 202 equine ovaries obtained from an abattoir. A
      total of 667 oocytes (3.3 per ovary) were recovered from 1023 follicles (recovery
      rate, 65%). Oocytes underwent IVM for 41 +/- 2 h (mean +/- S.D.), before being
      subjected to xenogenous gamete intrafallopian transfer (XGIFT). An average of 13
      +/- 0.8 oocytes and 40x10(3) spermatozoa per oocyte were transferred into 20
      oviducts of ewes. Fourteen percent of transferred oocytes (36/259) were recovered
      between 2 and 7 days post-XGIFT and 36% of those recovered displayed embryonic
      development ranging from the 2-cell to the blastocyst stage. Fertilization
      following XGIFT was also demonstrated by the detection of zinc finger protein Y
      (ZFY) loci. Ligation of the uterotubal junction (UTJ), ovarian structures, or the
      duration of oviductal incubation did not significantly affect the frequency of
      embryonic development or recovery of oocytes/embryos after XGIFT. In conclusion,
      equine embryos can be produced in a smaller non-equine species that is easier for
      handling.

PMID- 14662138
TI  - Effects of a GnRH agonist on oocyte number and maturation in mice superovulated
      with eCG and hCG.
AB  - The objective was to investigate the effects of a gonadotropin-releasing hormone
      agonist (GnRH) on ovulation rate and the number and maturation of oocytes in mice
      superovulated with equine chorionic gonadotropin (eCG) and human chorionic
      gonadotropin (hCG). Thirty 3-month-old BALB/C female mice (weight: 25-30 g) were
      assigned to three experimental groups: control, superovulated, and superovulated
      with GnRH pretreatment (n=10 per group). Control mice received an i.p. injection
      of 0.1 ml physiological saline solution. Superovulation was induced with 5 IU eCG
      (i.p.) and 5 IU hCG 48 h later. Mice in the superovulated with GnRH pretreatment
      group were given GnRH (20 mg/kg Fertirelin, i.m.), 24 h before superovulation.
      Thirteen hours after hCG administration, mice were sacrificed by cervical
      dislocation and blood samples were collected to determine serum progesterone
      concentration (by radioimmunoassay). Ovaries and oviducts were also harvested to
      enumerate corpora lutea and cumulus-enclosed oocytes. Progesterone concentrations
      were not significantly different among groups. The oocyte number and the
      maturation, ovulation rate, and the number of corpora lutea were higher in GnRH
      treated mice than both controls and superovulated mice. In conclusion, GnRH given
      24 h before superovulation with eCG-hCG increased the number and maturation of
      oocytes and the rate of ovulation in mice.

PMID- 14662139
TI  - Improved conception in timed-artificial insemination using a progesterone
      releasing intravaginal device and Ovsynch protocol in postpartum suckled Japanese
      Black beef cows.
AB  - The primary objective was to determine the effect of supplemental progesterone,
      administered via an intravaginal device (CIDR), on conception rates to timed
      artificial insemination (timed-AI) in postpartum suckled Japanese Black beef cows
      treated with the Ovsynch protocol. A secondary objective was to compare the
      effects of treatments on plasma concentrations of progesterone and estradiol.
      Cows in the control group (Ovsynch, n=38) received a standard Ovsynch protocol
      (100 microg GnRH analogue on Day 0, 500 microg PGF2alpha analogue on Day 7, and
      100 microg GnRH analogue on Day 9), with AI on Day 10, approximately 20 h after
      the second GnRH treatment. Cows in the treatment group (Ovsynch+CIDR; n=40)
      received a standard Ovsynch protocol plus a CIDR for 7 days (starting on Day 0).
      Plasma progesterone concentrations were determined on Days 0, 1, 7, 9, 10, and 17
      and plasma estradiol-17beta concentrations were determined on Days 7, 9, 10, and
      17. The odds ratio for likelihood of conception was 3.29 times greater (P=0.02)
      in the Ovsynch+CIDR group compared to Ovsynch group. The conception rate was
      greater (P=0.03) in the Ovsynch+CIDR group than in the Ovsynch group (72.5%
      versus 47.7%). Insertion of a CIDR device significantly increased plasma
      progesterone concentrations only on Days 1 and 7 (P<0.001 and P=0.05,
      respectively), but had no significant effect on plasma estradiol-17beta
      concentrations. Including a CIDR with the Ovsynch protocol significantly improved
      conception rates in postpartum suckled Japanese Black beef cows.

PMID- 14662140
TI  - Induction of ovulation in nonlactating dairy cows and heifers using different
      doses of a deslorelin implant.
AB  - The objective of this study was to evaluate ovarian function after inducing
      ovulation with a deslorelin implant in nonlactating dairy cows and heifers.
      Cattle received GnRH on Day -9, and PGF2alpha on Day -2. On Day 0, in Experiment
      1, cows received either 100 microg GnRH (Control), a 750 microg (DESLORELIN 750)
      or 1000 microg (DESLORELIN 1000) deslorelin implant. On Day 0, in Experiment 2,
      cows received 100 microg of GnRH or a 450 microg (DESLORELIN 450) deslorelin
      implant. In Experiments 1 and 2, cows received PGF2alpha on Day 16.
      Ultrasonography and blood sampling for plasma progesterone (P4) were used to
      monitor ovarian activity. On Day 0, in Experiment 3, heifers received either 100
      microg of GnRH or 750 microg (DESLORELIN 750) deslorelin implant. On Day 16, all
      heifers received PGF2alpha. Blood samples were collected on Days 7, 13 and 16. In
      Experiments 1-3, deslorelin implants did not elevate plasma concentrations of P4
      in a systematic manner during the late luteal phase. In Experiments 1 and 2,
      deslorelin implants decreased the size of the largest follicle and the number of
      Class II and III follicles. In Experiments 1 and 2, deslorelin-treated cows
      failed to ovulate by Day 28. In conclusion, deslorelin implants induced
      ovulation, stimulated development of a normal CL, and delayed follicular growth
      during the subsequent diestrus period. For future applications, the dose of the
      deslorelin implant will have to be adjusted, and if used for timed-inseminations,
      nonpregnant cows will have to be resynchronized to minimize delayed returns to
      estrus and ovulation.

PMID- 14662141
TI  - Effect of a deslorelin implant in a timed artificial insemination protocol on
      follicle development, luteal function and reproductive performance of lactating
      dairy cows.
AB  - This study examined the influence of a GnRH agonist containing either 450 or 750
      microg of deslorelin in an implant form or a gonadorelin injection (control) to
      induce ovulation in the Ovsynch protocol on pregnancy rates (PR), embryonic loss,
      and ovarian function in 593 lactating Holstein cows. Cows were given two
      injections of PGF2alpha 14 days apart, followed 14 days later by the Ovsynch
      protocol, and were timed artificially inseminated (TAI) at 68 +/- 3 days
      postpartum. Blood samples for determination of plasma progesterone concentrations
      were collected at 24 and 10 days prior to and 11 days after TAI. Pregnancy was
      diagnosed on Day 27 and reconfirmed on Day 41 after TAI. Non-pregnant, not re
      inseminated cows at Day 27 had their ovaries examined by ultrasonography, and the
      number and size of follicles and presence of luteal tissue were determined.
      Simultaneously, these cows were re-synchronized with the Ovsynch protocol.
      Pregnancy during the re-synchronization period was determined between 35 and 41
      days after insemination. On Day 27, PR were higher for control (39.0%) and
      deslorelin 450 microg (DESLORELIN 450) implant (41.3%) than for those receiving
      the deslorelin 750 microg (DESLORELIN 750) implant (27.5%; P<0.05). Pregnancy
      losses tended to decrease for DESLORELIN 450 compared with control (5.0% versus
      12.7%; P<0.13). Plasma progesterone concentrations did not differ significantly
      among treatments. Deslorelin suppressed ovarian activity and decreased PR during
      the re-synchronization period compared with control. The percentage of non
      pregnant animals that were re-inseminated by Day 27 was less for deslorelin
      compared with control. In conclusion, incorporation of an implant of the GnRH
      agonist deslorelin to induce ovulation in the Ovsynch protocol has the potential
      to reduce pregnancy losses, but the response was dependent upon implant
      concentration. Evaluation of lower doses to minimize the negative effects on
      subsequent fertility is warranted.

PMID- 14662142
TI  - Effect of dietary phosphorus concentration on estrous behavior of lactating dairy
      cows.
AB  - The objective of this study was to determine the effect of dietary phosphorus (P)
      concentrations of 0.38 (adequate) or 0.48% (excess) of the total mixed ration
      (TMR) (dry matter basis) on estrous behavior of lactating cows as measured by a
      radiotelemetric system (HeatWatch; De Forest, WI, USA). At calving, 42 Holstein
      cows (n=21 per treatment) were randomly assigned to one of two dietary P
      treatments. Cows were milked twice daily and milk weights were recorded. Cows
      were housed in a free-stall barn and were fitted with a radiotelemetric
      transmitter 40 days postpartum to record estrous mounting activity. The total
      number of estruses recorded for the 42 cows were 72 (37 and 35 for cows in the
      adequate and excess P groups, respectively). The mean duration of estrous cycles
      was 22 +/- 0.6 days and 21 +/- 0.4 days for cows fed the adequate and excess P
      diets, respectively (P=0.14). The mean duration of estrus was 8.9 +/- 1.1 h and
      8.6 +/- 1.2 h (P=0.86), the average number of mounts during estrus was 7.0 +/-
      1.2 and 8.2 +/- 1.7 (P=0.57), and the total mounting time was 27.1 +/- 4.3 s and
      30.8 +/- 6.5 s (P=0.64) for cows fed the adequate and excess P diets,
      respectively. Phosphorus treatment had no significant effect on intensity or
      duration of estrus.

PMID- 14662143
TI  - Localization of angiotensin II in pig ovary and its effects on oocyte maturation
      in vitro.
AB  - The renin-angiotensin system (RAS) has been found in mammalian ovarian tissue;
      however, its physiological role is unclear. This study examined the content of
      angiotensin II (Ang II) in porcine follicular fluid (pFF), Ang II localization
      and its receptors in ovary, and the effects of Ang II on porcine oocyte
      maturation. The concentrations of Ang II were 6951.82 +/- 1295.83, 3502.99 +/-
      679.10, 3147.89 +/- 690.60, and 2545.92 +/- 407.01 pg/ml in pFF from small,
      medium, large, and extra-large follicles, respectively. In addition, Ang II was
      found on zona pellucidae (ZP) and granulosa cells by immunoreactive staining. The
      distribution of AT1, an Ang II receptor subtype, was in accordance with that of
      Ang II. However, AT2, another Ang II receptor, was mainly distributed in the
      stroma and thecal layers of follicles. When oocytes were cultured in media
      containing various concentrations of Ang II, a higher (P<0.05) proportion of
      oocytes reached metaphase II (MII) in the medium with 100 ng/ml (87.0%) than
      without Ang II (61%). When oocytes from different sizes of follicles were
      separately cultured in media containing 100 ng/ml Ang II, maturation rates were
      significantly higher in oocytes from small (61.5%) and medium (85.1%) follicles
      than that of their controls (45.1 and 72.6%, respectively). However, addition of
      Ang II inhibited nuclear maturation in oocytes from large follicles (77.8% versus
      87.3%). Fertilization and male pronuclear (MPN) formation rates of oocytes
      matured in medium containing 100 or 1000 ng/ml of Ang II were higher (P<0.05)
      than that of oocytes matured in medium containing 0 or 10 ng/ml Ang II.
      Glutathione content in oocytes cultured for 44 h in medium containing 100 or 1000
      ng/ml of Ang II was also higher (P<0.01) than that of oocytes cultured in medium
      containing 0 or 10 ng/ml Ang II. In conclusion, Ang II was present in porcine
      ovaries and may regulate follicle growth and oocyte maturation.

PMID- 14662144
TI  - Effects of lowered temperatures and media on short-term preservation of zebu (Bos
      indicus) preantral ovarian follicles.
AB  - The maintenance of follicle quality during the transportation of ovaries is
      essential for the successful cryopreservation and in vitro development of
      preantral follicles. The objective of this study was to evaluate the effect of
      cooling ovarian tissue on the conservation of zebu cow preantral follicles.
      Ovarian pieces were immersed in saline or coconut water (CW) solutions and
      maintained at 4 or 20 degrees C for 6, 12, or 18 h. Preantral follicles were
      evaluated by histology and transmission electron microscopy. Storage of ovarian
      pieces at 20 degrees C for 12 or 18 h significantly reduced the percentage of
      morphologically normal follicles compared to controls. In contrast, conservation
      at 4 degrees C for up to 18 h and at 20 degrees C for up to 6 h kept the
      percentage of normal follicles similar to controls. However, the type of solution
      that the ovaries were immersed in had little effect on the results. Decreased
      cellular metabolism probably accounted for better preservation of preantral
      follicles at 4 degrees C. In conclusion, zebu cow ovaries were successfully
      stored at 4 degrees C for up to 18 h with no morphological damage to preantral
      follicles. However, at 20 degrees C, ovaries could only be stored for 6 h.

PMID- 14662145
TI  - Ovarian follicle development in wapiti (Cervus elaphus) during the anovulatory
      season.
AB  - The ovaries of 12 mature wapiti hinds were studied by transrectal ultrasonography
      during the anovulatory season to characterize follicular dynamics and to test the
      hypothesis that follicle development occurs in a wave-like fashion. The hinds
      were examined daily, standing without sedation. Follicle size and numbers were
      recorded, and individual follicles were identified serially. Follicle development
      was considered wave-like if periodic changes in follicle numbers could be
      associated temporally with the development of a dominant follicle. There were non
      random changes (P<0.01) in the number of follicles > or =4 mm in diameter
      detected per day. Each peak in follicle numbers was associated with the
      development of a single dominant follicle. The dominant follicle of the cohort
      was larger (P<0.05) than the other follicles 1 day after its emergence. Intervals
      between successive peaks (6.8 +/- 0.4 day) and troughs (6.8 +/- 0.4 day) in
      follicle numbers, and emergence of sequential dominant follicles (7.1 +/- 0.5
      day) were not different (P=0.86). Results confirmed the hypothesis that ovarian
      follicles develop in a wave-like fashion in wapiti during the anovulatory season.

PMID- 14662146
TI  - Effect of folic acid plus glycine supplement on uterine prostaglandin and
      endometrial granulocyte-macrophage colony-stimulating factor expression during
      early pregnancy in pigs.
AB  - The objective was to determine the effects of folic acid+glycine supplement on
      uterine metabolism of prostaglandin and mRNA expression of endometrial
      granulocyte-macrophage colony-stimulating factor (GM-CSF) in nulliparous (NYL)
      and multiparous Yorkshire-Landrace (YL) sows, and in multiparous Meishan-Landrace
      sows (ML). In each of these three groups, sows were randomly assigned to two
      treatments: 15 ppm folic acid+0.6% glycine or no supplement. The dietary
      supplement was given from the estrus before mating to slaughter on Day 25 of
      pregnancy. At slaughter, endometrial tissue was collected to determine
      endometrial expression levels of GM-CSF mRNA, cyclooxygenase-1 (COX1) and -2
      (COX2) and to evaluate in vitro endometrial secretion of prostaglandin E2 (PGE2)
      secretion. Allantoic fluid samples were also collected to determine the
      concentration of PGE2, prostaglandin F2alpha (PGF2alpha), estradiol-17beta (E2),
      progesterone (P4), and transforming-growth factor-beta2 (TGF-beta2). The
      allantoic contents of PGF2alpha, E2 and P4, and endometrial in vitro secretion of
      PGE2 were not significantly influenced by the folic acid+glycine supplement. The
      folic acid+glycine supplement tended (P<0.07) to increase allantoic content of
      PGE2 and TGF-beta2 in all sows and increased (P<0.05) endometrial expression of
      COX2, especially in NYL sows. The endometrial expression of COX1 was decreased
      (P<0.05) by folic acid+glycine supplement, especially in multiparous YL sows. The
      allantoic contents of PGE2 and PGF2alpha were not significantly affected by sow
      type. However, NYL sows had higher (P<0.05) endometrial in vitro secretion of
      PGE2 and allantoic content of P4 than multiparous YL and ML sows. The allantoic
      content of E2 was also higher (P<0.05) in NYL sows than in multiparous ML sows
      only. The allantoic content of TGF-beta2 was lower (P<0.05) in multiparous ML
      than in multiparous YL only sows. Finally, in YL and NYL sows, folic acid+glycine
      supplement decreased (P<0.05) the endometrial expression of GM-CSF but not in ML
      sows. In summary, folic acid+glycine supplement altered endometrial expression of
      GM-CSF and uterine metabolism of prostaglandins during the post-attachment period
      of porcine embryos but some of these effects were manifest only in Meishan and
      nulliparous sows.

PMID- 14662147
TI  - Transrectal Doppler sonography of uterine and umbilical blood flow during
      pregnancy in mares.
AB  - Transrectal color Doppler sonography was used to investigate uterine and
      umbilical blood flow during pregnancy (duration, 46-48 weeks) in four mares. The
      resistance index (RI) and blood flow volume (VOL) of the uterine arteries
      ipsilateral and contralateral to the conceptus, and the presence of an early
      diastolic notch in the Doppler wave, were evaluated every 4 week throughout
      pregnancy. Fetal blood flow was calculated semiquantitatively every 2 week (from
      20 to 40 weeks), using the RI of the umbilical arteries. During the entire period
      of investigation, there were no significant individual variations in uterine RI
      and VOL nor differences between the two uterine arteries. Mean RI decreased by
      more than half during pregnancy from 0.89 +/- 0.01 to 0.39 +/- 0.03, and mean VOL
      increased almost 400-fold from 69 +/- 37 to 27,467 +/- 8851 ml/min. There were
      relationships (P<0.0001) between week of pregnancy (x) and RI as well as VOL.
      These were described by the equations RI=0.938-0.150 ln(x) and VOL
      (ml/min)=7.621x(2.157). Log transformed total estrogen (TE) were related to RI
      (r=-0.879; P<0.05) as well as to VOL (r=0.888; P<0.05). The notch in the Doppler
      wave of the uterine artery disappeared between 18 and 26 weeks. There was a
      correlation (P<0.0001) between week of gestation (x) and RI values of the
      umbilical arteries; this was described by the equation RI=1.763-0.071x+0.001x2.
      Further studies are needed to determine whether transrectal color Doppler
      sonography could be used to identify mares at risk of abortion.

PMID- 14662148
TI  - Testicular thermoregulation in Bos indicus, crossbred and Bos taurus bulls:
      relationship with scrotal, testicular vascular cone and testicular morphology,
      and effects on semen quality and sperm production.
AB  - Mechanisms of testicular thermoregulation, the relationship of scrotal,
      testicular vascular cone (TVC), and testicular morphology with thermoregulatory
      capability, and their effects on semen quality and sperm production were studied
      in 20 Bos indicus, 28 crossbred, and 26 Bos taurus bulls. The ratio of testicular
      artery length and volume to testicular volume were larger (P<0.05) in B. indicus
      and crossbred bulls than in B. taurus bulls (1.03 and 0.94 cm/cm3 versus 0.48
      cm/cm3; 0.034 and 0.047 ml/cm3 versus 0.017 ml/cm3, respectively). Testicular
      artery wall thickness (average 192.5, 229.0, and 290.0 microm, respectively) and
      arterial-venous blood distance in the TVC (average 330.5, 373.7, and 609.4
      microm, respectively) were smallest in B. indicus, intermediary in crossbred, and
      greatest in B. taurus bulls (P<0.05); the proximity between arterial and venous
      blood was consistent with the estimated decrease in arterial blood temperature
      after passage through the TVC (5.9, 5.0, and 2.9 degrees C, in B. indicus,
      crossbred, and B. taurus bulls, respectively). In crossbred and B. taurus bulls,
      there was a positive top-to-bottom scrotal temperature gradient and a negative
      testicular subtunic temperature gradient. However, in B. indicus bulls, both
      scrotal and testicular subtunic temperatures gradients were positive. Differences
      in the vascular arrangement, characteristics of the artery (e.g. wall thickness)
      or thickness of the tunica albuginea may have affected the testicular arterial
      blood and subtunic temperatures in B. indicus bulls. Better testicular
      thermoregulatory capability was associated with increased scrotal shape
      (pendulosity), testicular artery length and volume, and top-to-bottom gradient of
      the distance between the artery wall and the veins in the TVC. Increased semen
      quality was associated with increased testicular volume and scrotal subcutaneous
      (SQT) temperature gradient, and with decreased scrotal surface and testicular
      temperatures. Increased sperm production was associated with increased testicular
      artery volume, testicular volume, and SQT temperature gradient, and with
      decreased testicular artery wall thickness, scrotal circumference (SC), and
      scrotal surface, testicular subtunic, and epididymal temperatures. In conclusion,
      morphology of the TVC may contribute to the greater resistance of B. indicus
      bulls to high ambient temperatures by conferring a better testicular blood supply
      and by facilitating heat transfer between the testicular artery and veins.
      Testicular thermoregulation was associated with opposing scrotal and testicular
      subtunic temperatures gradients only in crossbred and B. taurus bulls. Scrotal,
      TVC, and testicular morphology influence testicular thermoregulatory capability
      and were associated with differences in semen quality and sperm production.

PMID- 14662149
TI  - The effects of diminazene aceturate and ceftriaxone on ram sperm.
AB  - Effects of diminazene aceturate and ceftriaxone disodium were evaluated on sperm
      quality of rams. Daily intramuscular injections of diminazene (6 mg/kg) or
      ceftriaxone (28.5 mg/kg) were given to each of seven Akkaraman rams assigned per
      drug for two days. Semen samples were collected from the rams at post-treatment
      1, 4, 24, 48, 72, 144, 288 and 336 h and examined for sperm characteristics and
      hyaluronidase activity. Results showed that use of ceftriaxone and diminazene
      caused significant (P<0.01) decreases in sperm concentration, volume and motility
      compared to control group within 288 h post-treatment. In addition, hyaluronidase
      activity increased significantly (P<0.01) in semen of rams treated with
      ceftriaxone while remained unchanged in those received diminazene. In conclusion,
      diminazene aceturate and ceftriaxone disodium did not have any deleterious effect
      on hyaluronidase enzyme. However, both drugs caused impairment of sperm in rams
      during the 288 h.

PMID- 14662150
TI  - Effects of n-3 polyunsaturated dietary supplementation on the reproductive
      capacity of male turkeys.
AB  - To measure the effects of dietary n-3 polyunsaturated fatty acid (PUFA)
      supplementation on the reproductive capacity of adult male turkeys in industrial
      flocks, the males of 22 commercial farms were fed either a standard diet or a
      fish oil diet enriched in n-3 PUFAs. The fatty acid composition of the
      spermatozoa and reproductive performance were measured throughout the
      reproductive period. The fish oil diet very effectively increased the percentage
      of n-3 fatty acids (FA) (22:5n-3 and 22:6n-3) in spermatozoa and correspondingly
      decreased the percentage of n-6 PUFAs (20:4-6 and 22:4n-6): the n-3/n-6 ratio in
      spermatozoa fatty acids were 0.04-0.07 with the standard diet and 0.32-0.4 with
      the fish oil diet. These changes did not affect the spermatozoa content of n-9
      PUFAs, particularly of 22:3n-9 which is abundant in turkey spermatozoa (9-12% of
      the total fatty acids). The supplementation was effective in the middle as at the
      end of the reproductive period. The reproductive capacity of males was modified
      by the diet and the positive effect of the n-3 supplemented diet increased with
      age (increase in hatching rates of nearly 2 points at 48-58 weeks for males fed
      fish oil diet). These results indicate that an increase in the dietary ratio of n
      3/n-6 PUFAs is valuable to sustain the reproductive capacity of male turkeys
      especially when they are getting older.

PMID- 14662151
TI  - Influence of sperm:oocyte ratio during in vitro fertilization of in vitro matured
      cumulus-intact pig oocytes on fertilization parameters and embryo development.
AB  - The present study was conducted to evaluate the influence of sperm:oocyte ratio
      during in vitro fertilization (IVF) of in vitro matured cumulus-intact oocytes on
      fertilization parameters and embryo development in pigs. In vitro matured oocytes
      surrounded by intact cumulus cells (COC) were inseminated with frozen-thawed
      spermatozoa at different sperm:oocyte ratios (2000:1, 3000:1, 4000:1, 6000:1, and
      8000:1). Denuded oocytes inseminated with 2000 frozen-thawed spermatozoa:oocyte
      were the control group. A total of 2546 oocytes in five replicates were exposed
      to spermatozoa for 6 h and then cultured in embryo culture (EC) medium for 6 h
      (pronuclear formation) or 7 days (blastocyst formation: BF). The penetration rate
      increased in the COC groups with the sperm:oocyte ratio, reaching the highest
      rates with 8000:1 spermatozoa:oocyte (72.1 +/- 6.5%), similar to the control
      (73.5 +/- 3.5%). However, the monospermy was highest with the lower
      spermatozoa:oocyte rates (82.6-94.8%) and decreased drastically (P<0.05) in the
      COC group fertilized with 8000 sperm:oocyte (36%). The efficiency of
      fertilization (number of monospermic oocytes/total number of inseminated oocytes)
      showed no difference among the COC groups (20-30%) but they were significantly
      lower (P<0.007) than those obtained by the control group (43.7 +/- 2%). Embryo
      development was highest in the control group (58% for cleavage and 23% for BF)
      but not significantly different with the 6000 and 8000 sperm:oocyte COC groups
      (47 and 50% for cleavage and 19 and 17% for BF, respectively). These results
      indicate that the use of COC for IVF involves a drop in the efficiency of the
      fertilization and the necessity to increase the frozen-thawed sperm:oocyte ratio
      three to four times more to obtain similar embryo development to denuded oocytes.

PMID- 14662152
TI  - Amino acid metabolism of preimplantation bovine embryos cultured with bovine
      serum albumin or polyvinyl alcohol.
AB  - Bovine serum albumin (BSA) is an embryotrophic macromolecule used in embryo
      culture media, which is commonly replaced with synthetic compounds, such as
      polyvinyl alcohol (PVA). This study compared the effect of BSA and PVA on the
      development, blastocyst cell number and amino acid metabolism of preimplantation
      bovine embryos in vitro. Embryos were produced by in vitro maturation and
      fertilization of immature oocytes from abattoir-derived ovaries. Zygotes were
      cultured in synthetic oviduct fluid with either 4 mg/ml BSA (SOFaaBSA) or 1 mg/ml
      PVA (SOFaaPVA) in microdrops with a mineral oil overlay at 39 degrees C under a
      5% O2/5% CO2/90% N2 atmosphere. Blastocyst rate and cell numbers were determined
      after 123 h of culture. In parallel, single expanding blastocysts grown in either
      medium were incubated in microdrops for 12 h. Amino acid profile of spent drops
      was determined by high performance liquid chromatography. Replacing BSA with PVA
      depressed blastocyst rate and cell numbers, and led to quantitative and
      qualitative differences in amino acid appearance, disappearance and turnover.
      These differences could partly be due to an increase in free intracellular amino
      acid concentration in SOFaaBSA embryos derived from hydrolysis of endocytosed
      BSA, and argue against the inclusion of PVA in bovine embryo culture media.

PMID- 14662153
TI  - Sex ratios in mule duck embryos at various stages of incubation.
AB  - Mule duck hatcheries have long reported varying degrees of unbalance in the sex
      ratio, with a preponderance of male mules at hatching. The aim of the present
      study was to assess the distributions of sex ratios at various stages of
      development in embryos originating from intra- and intergeneric crosses between
      parental lineages (Muscovy male x Muscovy female, Pekin male x Pekin female,
      Muscovy male x Pekin female or Mule, and Pekin male x Muscovy female or Hinny).
      In Experiment I, embryo sexing was performed on Days 1 and 5 of incubation (by
      multiplex PCR) and at hatching (by vent observation). The sex ratio was not
      significantly modified during the early stages of embryo development whatever the
      genetic origin (P>0.05, Days 1 and Day 5) but our results in mule and hinny
      ducklings confirmed the preponderance of males among normally hatched ducklings
      originating from the intergeneric lineage (58.9 and 55.4% males in mules and
      hinnies, respectively; P<0.05 in both cases). Sex ratio (vent sexing) in second
      grade (cull) ducklings revealed that 68% of these ducklings were females
      (P<0.05). In Experiment II, the distribution of sex ratio was also performed in
      mule duck eggs from 6 batches (400,000 eggs/batch) first examined for fertility
      (candling) on Day 18 of incubation. These results indicate that the percentage of
      males present in the population of normally hatched ducklings increases when
      fertility decreases. In addition, this experiment also revealed that 83.7-90.5%
      of viable male mule embryos develop up to hatching, compared to only 43.0-51.0%
      of female mule embryos. Given that a deviation in sex ratio during the first
      stages of incubation is unlikely (Experiment I), it is concluded that the skewed
      sex ratio of mule ducks at hatching is primarily due to increased late mortality
      in female mule embryos occurring between egg transfer and hatching. This
      mortality originated, at least in part, from the intergeneric origin of female
      mules, and was marked to a greater or lesser extent depending on the initial
      success of fertilization in a given batch, a possible indication that the initial
      quality of gametes may selectively exert its influence at the later stages of
      embryo development.

PMID- 14662154
TI  - Development of antral follicles in cryopreserved cat ovarian tissue transplanted
      to immunodeficient mice.
AB  - Ovarian cortex cryopreservation and xenotransplantation into immunodeficient mice
      represents a potential means for female germplasm conservation and an immediate
      model for investigation of folliculogenesis. The objectives of this study were
      to: (1) assess follicle survival after cryopreservation and transplantation of
      cat ovarian tissue into non-obese diabetic severely combined immunodeficient (NOD
      SCID) mice; and (2) evaluate the effects of gonadotropin treatments on follicular
      development in the transplanted tissue. Slices from the cat ovarian cortex were
      frozen and after thawing, transplanted under each kidney capsule of castrated
      male NOD SCID mice (eight xenografts in four mice). Sixty-two days after surgery,
      mice were randomly assigned (two per group) to gonadotropin-treated (eCG and hCG
      88 h later) or control (saline-treated) groups. Twenty-four hours after the last
      injection, ovarian tissue was recovered and processed for histology. Fresh
      ovarian tissue from the same original source was similarly processed. Follicles
      were counted, measured, and classified as primordial, primary, secondary, or
      antral. Immunoreactive proliferating cell nuclear antigen (PCNA) stain was used
      to assess follicle viability. Microscopic examination revealed no evidence of
      necrosis or fibrosis. The grafts were well-vascularized, with follicles at all
      stages of development. Numbers of follicles in the transplanted tissue were
      markedly reduced compared to fresh tissue, with approximately 10% of follicles
      surviving freezing and transplantation procedures. Growing follicles positive for
      PCNA were found in all xenografts. Gonadotropin treatment did not alter the
      proportion of resting to growing follicles or mean follicle diameter by
      comparison with controls from untreated mice. By contrast, luteinization, but not
      ovulation, of antral follicles was observed only in grafts from treated mice. In
      summary, frozen-thawed cat ovarian cortex tissue not only survived
      xenotransplantation, it also contained follicles able to grow to antral stages.
      Exogenous gonadotropin treatment in this model resulted in luteinization of
      antral follicles but enhancement of follicular growth and ovulation did not
      occur.

PMID- 14662155
TI  - Diagnosis and treatment of four stallions, carriers of the contagious metritis
      organism--case report.
AB  - Contagious Equine Metritis (CEM), a venereal disease of horses caused by the
      bacterium Taylorella equigenitalis, was first diagnosed in 1977 and subsequently
      spread to many nations [Proc 24th AM Assoc Equine Pract (1979) 287]. The disease
      was confirmed in the United States in 1978 [Proc Am Assoc Equine Pract (1983)
      295]. Specific regulatory procedures for this disease have been established in
      the United States and 37 other countries. From 1999 through 2001, four of 120
      imported European stallions tested positive for CEM at a quarantine facility in
      Darlington, MD, USA. Two stallions were identified by positive bacterial cultures
      for T. equigenitalis on arrival. The other two positive stallions were negative
      on initial bacterial cultures, but were identified as CEM carriers when test
      mares (that they had mated) were culture-positive for T. equigenitalis. Since T.
      equigenitalis, is a fastidious slow-growing coccobacillus, additional sets of
      samples taken over a interval might be required to ensure positive stallions are
      detected before mating test mares. Likewise, additional sets of samples taken
      over a long interval after treatment of a stallion for CEM might be required to
      ensure that positive stallions treated for CEM are detected before mating test
      mares. Aggressive systemic antibiotic therapy accompanied by routine topical
      therapy might be required to treat some CEM-positive stallions.

PMID- 14662156
TI  - Corticosteroids in pregnancy: is further research needed?

PMID- 14662157
TI  - Infection-related perinatal brain injury: the pathogenic role of impaired fetal
      cardiovascular control.
AB  - There is a growing body of evidence from clinical and epidemiologic studies that
      in utero exposure to infection plays an important role in the genesis of fetal or
      neonatal injury leading to cerebral palsy and chronic lung disease. Thus, after
      chorioamnionitis the incidence of immature neonates with periventricular white
      matter damage and periventricular or intraventricular hemorrhage is significantly
      elevated. Recent clinical and experimental data support the hypothesis that a
      fetal inflammatory response links antenatal infection with brain white matter
      damage and subsequent motor handicap. A variety of studies support the view that
      cytokines released during intrauterine infection directly cause injury to the
      immature brain. In this review, we provide evidence that in utero exposure to
      bacterial infection can severely alter fetal cardiovascular function, resulting
      in dysregulation of cerebral blood flow and subsequent hypoxic-ischemic brain
      injury.

PMID- 14662158
TI  - Protease-activated receptor isoform expression in pregnant and nonpregnant rat
      myometrial tissue.
AB  - OBJECTIVE: Three protease-activated receptor (PAR1, 3, and 4) isoforms have been
      shown to be responsible for the cellular effects of thrombin; another PAR isoform
      (PAR2) is responsible for the cellular effects of trypsin. The present studies
      sought to test the hypothesis that one (or more) of these PAR isoforms is
      expressed in myometrial tissue, thereby accounting for the uterotonic effects of
      these novel agonists. METHODS: The rat PAR3 and 4 isoforms were cloned from a rat
      spleen cDNA library. PAR isoform mRNA expression was determined by using reverse
      transcriptase polymerase chain reactions (PCR) in Sprague-Dawley rats.
      Confirmation of the identity of the amplified mRNA was done by sequence analysis.
      Relative quantification of the PAR1 and PAR2 isoforms was performed using a real
      time quantitative reverse transcriptase PCR (RT-PCR) technique. PAR protein
      expression was confirmed by Western blots using polyclonal antibodies. RESULTS:
      The rat PAR3 and 4 homologues showed significant sequence homology to the mouse
      and human amino acid and nucleotide sequences. The RT-PCR studies confirmed PAR1
      4 expression in myometrium from rats in estrus. PAR3 was expressed in uterus,
      spleen, kidney, liver, lung, brain, and heart. PAR4 was expressed in uterus,
      spleen, and lung. Messenger RNA for the PAR1 and 2 isoforms was expressed during
      the second half of gestation in myometrium from timed-pregnant rats. In contrast,
      mRNA for the PAR3 and 4 isoforms was not detected in gestational myometrium. PAR
      protein expression appeared to match tissue mRNA expression patterns. CONCLUSION:
      These RT-PCR studies confirmed ubiquitous expression of the PAR1 and PAR2
      isoforms in myometrium and other rat tissues; in contrast, the PAR3 and PAR4
      isoforms are expressed in a tissue-specific and gestationally related pattern.

PMID- 14662159
TI  - Betamethasone in the last week of pregnancy causes fetal growth retardation but
      not adult hypertension in rats.
AB  - We tested the hypotheses that (1) maternal betamethasone (betaM) treatment over
      the range of clinical doses for prevention of prematurity-related pathologies
      from day 15 to 21 of rat gestation would produce growth retardation, and (2) the
      lowest betaM dose to produce growth retardation would result in hypertension in
      adult offspring. In experiment 1, pregnant Sprague-Dawley rats were administered
      betaM (0, 50, 100, 200, 400, or 600 microg/kg per day, subcutaneously) on days 15
      21 of pregnancy and necropsied on day 21.5, with fetal lung and placental weights
      recorded. In experiment 2, two more groups of rats (0 or 100 microg/kg per day,
      subcutaneously) were allowed to deliver, and offspring were instrumented at 100
      +/- 4 days of postnatal life with indwelling left carotid arterial catheters.
      After 48 hours of recovery, blood pressure was recorded continuously for 24
      hours. In experiment 1, all newborn rats treated with betaM, and their placentas,
      except those receiving 50 microg/kg per day, were growth retarded in comparison
      with controls (P <.05). All treated lungs were smaller than those of controls (P
      <.05). In experiment 2, no differences were found in the mean arterial blood
      pressure of adult offspring given the lowest effective dose of betaM (100
      microg/kg per day) compared with controls (114.2 +/- 5.3 mmHg versus 114.6 +/-
      3.4 mmHg, respectively). These data suggest that glucocorticoids given in the
      last week of rat pregnancy in the lowest human clinical dose do not cause
      hypertension and somatic growth retardation. However, the presence of lung growth
      restriction at this dose argues for more studies on the efficacy of even lower
      concentrations for their ability to improve lung and other organ and tissue
      function while avoiding unwanted side effects.

PMID- 14662160
TI  - Differential effects of maternal and fetal betamethasone injections in late
      gestation fetal sheep.
AB  - OBJECTIVE: To determine the effects of single or repeated intramuscular
      injections of betamethasone, given maternally or directly to the fetus, on
      chronically catheterized, late-gestation fetal sheep. METHODS: Fetal or maternal
      sheep received either repeated intramuscular injections of betamethasone (0.5
      mg/kg body weight at 104, 111, and 118 days' gestation), single betamethasone
      injection (at 104 days' gestation, followed by saline at 111 and 118 days'
      gestation), or repeated saline injections; n = 6 or 7 per group. At approximately
      130 days' gestation fetuses were catheterized for serial measurements of heart
      rate, arterial pressure, blood gases, metabolites, and electrolytes. RESULTS:
      Repeated maternal betamethasone injections reduced birth weight (P =.03) without
      fetal hypoxemia or hypoglycemia. Circulating fetal calcium and lactate
      concentrations were reduced (P =.002 and P =.014, respectively) by repeated
      maternal betamethasone only. Fetal hematocrit tended to be lower after fetal (P
      =.3) and maternal (P =.07) betamethasone. CONCLUSION: Growth restriction caused
      by repeated maternal betamethasone treatments is not due to overt chronic
      placental insufficiency but may be caused by alterations in hormonal mediators of
      fetal growth or impairment of placental transport of specific nutrients.

PMID- 14662161
TI  - Alterations in maternal corticosteroid levels influence fetal urine and lung
      liquid production.
AB  - OBJECTIVE: This study was designed to test the hypotheses that disruption of
      maternal adrenal secretion in late pregnancy requires fetal adaptations in order
      to maintain fetal blood volume and fetal viability. METHODS: Pregnant ewes were
      adrenalectomized at approximately 112 days, and cortisol and aldosterone were
      replaced to either normal pregnant levels (with 1 mg/kg per day of cortisol and 3
      microg/kg per day of aldosterone) or normal nonpregnant levels of aldosterone or
      cortisol (0.5 mg/kg per day of cortisol or 1.5 microg/kg per day of aldosterone).
      RESULTS: Fetal blood volume, blood pressure, lung liquid production, urine
      production, free water clearance, and glomerular filtration rate were measured at
      130 days. In a separate group, fetal organ blood flow was measured. Fetal blood
      volume was not significantly decreased by disruption of maternal corticosteroid
      secretion. However fetal urine production and free water clearance were reduced
      in fetuses of low cortisol or low aldosterone ewes. Fetal lung liquid secretion
      was also significantly reduced in the low aldosterone group. The glomerular
      filtration rate was reduced in fetuses of all adrenalectomized ewes, regardless
      of replacement dose. Fetal blood pressure was significantly reduced in the
      fetuses of low aldosterone ewes; blood flow to several fetal organs was increased
      in this group, indicating that decreased vascular resistance may contribute to
      the relative hypotension. CONCLUSION: Alterations in maternal adrenal
      corticosteroid levels resulted in fetal adaptation to maintain fetal blood volume
      despite relative maternal hypovolemia. These adaptations occurred at the expense
      of fetal urine and lung liquid production.

PMID- 14662162
TI  - 5-hydroxytryptamine and thromboxane A2 as physiologic mediators of human
      umbilical artery closure.
AB  - OBJECTIVE: This study investigated the response of the human umbilical artery to
      various agonists in order to determine which agents might be involved in
      umbilical cord closure. METHODS: Umbilical artery rings from 22 cesarean
      deliveries were suspended in tissue baths containing Krebs-Henseleit solution
      under low and normal oxygen conditions. Samples were challenged with 5
      hydroxytryptamine, acetylcholine, angiotensin II, bradykinin, endothelin-1,
      histamine, norepinephrine, phenylephrine, and U46619 (a thromboxane A(2)
      mimetic). RESULTS: Only 5-hydroxytryptamine, bradykinin, endothelin-1, histamine,
      and U46619 produced appreciable maximal contractions. Furthermore, although the
      contractile force generated by these agonists was diminished in normal oxygen
      conditions, this reduction affected responses to 5-hydroxytryptamine and U46619
      least. CONCLUSION: 5-Hydroxytryptamine and U46619 demonstrated the
      characteristics most likely to be associated with closure of the umbilical
      artery, ie, they elicited strong, sustained contractions at physiologic
      concentrations and under both normal and low-oxygen conditions. These data
      suggest that closure of the umbilical artery may be mediated by 5
      hydroxytryptamine and thromboxane A(2).

PMID- 14662163
TI  - cDNA microarray analysis of gene expression profiles in human placenta: up
      regulation of the transcript encoding muscle subunit of glycogen phosphorylase in
      preeclampsia.
AB  - OBJECTIVE: Third-trimester human placentas from normal and preeclamptic
      pregnancies were evaluated for possible changes in gene expression patterns by
      microarray analysis. METHODS: Placentas from four normal pregnancies and four
      pregnancies complicated by preeclampsia were studied. In a preliminary effort to
      identify possible differences between the two groups, complementary DNA (cDNA)
      probes were prepared from pooled total RNA by reverse transcription in the
      presence of (33)P-dCTP. After hybridization to human GeneFilter cDNA microarrays
      (GF211; Research Genetics, Huntsville, AL), 319 positive signals were detected
      above background out of a possible 4131 human cDNAs spotted on the filters.
      RESULTS: Ten most highly expressed mRNA species, ten most up-regulated, and ten
      most down-regulated genes in placentas from both groups of patients were
      identified for future studies. Of the 319 positive hybridizations, one transcript
      was clearly elevated in preeclamptic pregnancy. This cDNA encodes the muscle
      subtype of glycogen phosphorylase (GP-M) and was increased more than 2.8-fold (P
      <.05) in the preeclamptic placentas. In contrast, cDNA for glycogen synthase
      (muscle and liver isoforms) was not significantly increased, being near the
      limits of detection. The preeclampsia-induced increase of placental GP-M mRNA
      expression (approximately 3.5-fold) was confirmed by northern blot analysis.
      CONCLUSION: We conclude that microarray analysis can detect trends in mRNA and
      gene expression in placentas from normal and preeclamptic pregnancies that may be
      further studied in a more targeted fashion. We found that placental GP-M mRNA
      level is up-regulated in preeclampsia, which is consistent with previous reports
      of increased glycogen phosphorylase activity, and we suggest that it may be
      largely regulated at the level of transcription. Further studies may determine
      whether such up-regulation might be a response to hypoxia.

PMID- 14662164
TI  - Inability to detect cell free fetal DNA in the urine of normal pregnant women nor
      in those affected by preeclampsia associated HELLP syndrome.
AB  - OBJECTIVE: Recent reports have indicated that cell-free fetal DNA can be detected
      in the urine of pregnant women. We attempted to reproduce those data. METHODS:
      Urine samples were collected from 18 normal pregnant women (11 with a male
      fetus). Urinary DNA was examined by Y-chromosome-specific nested polymerase chain
      reaction (PCR) or real-time PCR. Samples were also examined from two pregnancies
      complicated by HELLP (hemolysis, elevated liver enzymes, and low platelets)
      syndrome, which had very high levels of cell-free fetal DNA in the maternal
      plasma. To validate our data, a quantitative comparison of different DNA
      extraction procedures used in the previous reports was performed. RESULTS: In no
      instance were we able to detect any fetal DNA in maternal urine, although copious
      quantities of cell-free fetal DNA were present in the maternal plasma of those
      pregnancies affected by HELLP syndrome. Our quantitative analysis of the various
      extraction procedures used indicated that the commercial column elution method we
      used was comparable, if not superior, to the noncommercial methods used in
      previous reports. CONCLUSION: Our data strongly suggest that cell-free fetal DNA
      is not readily detectable in maternal urine, even under conditions known to
      increase kidney permeability.

PMID- 14662165
TI  - Progesterone up-regulates WT1 mRNA and protein, and alters the relative
      expression of WT1 transcripts in cultured endometrial stromal cells.
AB  - OBJECTIVE: To determine the change in expression of the Wilms tumor suppressor
      gene product, WT1, by progesterone alone in endometrial stromal cell culture and
      to study its relationship with prolactin, a marker of decidualization. In
      addition, to examine the change in ratio of WT1 isoforms with and without exon 5
      message. METHODS: Endometrial biopsies were taken from eight patients who had
      hysterectomy. Stromal cells were isolated and cultured in the presence of
      progesterone alone (12 days) or progesterone and 8-bromo-cyclic adenosine
      monophosphate (cAMP) (6 days). RNA was extracted from cells, and reverse
      transcription, real-time polymerase chain reaction (PCR), and conventional PCR
      were done to analyze WT1 mRNA expression. Immunocytochemistry was performed on
      equivalent cells to study WT1 protein expression. Decidualization was identified
      by increased prolactin concentrations in the media and immunocytochemical markers
      IGFBP-1 and collagen IV. RESULTS: Reverse transcription and real-time PCR
      revealed a significant increase in WT1 mRNA with increasing progesterone
      concentrations when decidualization was occurring (n = 6, P =.002). Increasing
      progesterone concentrations also increased the proportion of the WT1 transcript
      containing a 17-amino-acid insert (+ exon 5 expression); changes in WT1 exon 5
      expression have been shown to be involved in control of proliferation and
      differentiation. Significant correlations between WT1 message and prolactin
      existed at physiologic progesterone concentrations (6.25, 12.5, 25, and 50 nM; P
      <.05) until prolactin concentrations reached a plateau at 100 nM. At
      concentrations of progesterone alone (> 25 nM) and progesterone with 8-bromo
      cAMP, WT1 protein was localized to the nuclei of many of the decidualized stromal
      cells. CONCLUSION: The changing expression of WT1 isoforms in endometrial stromal
      cells caused by progesterone may be important for differentiation into the
      decidualized phenotype.

PMID- 14662166
TI  - Hair cell re-growth.
AB  - Hair cell loss is usually a function of age, noise, ototoxic drugs and genetics.
      Therapeutic strategies fall into two categories: protection and regeneration.
      Protective methods include targeted application of growth factors and other
      agents to promote cell survival, and systemic application of drugs to prevent
      activation of programmed cell death. These strategies are related to treatments
      that cause predictable damage, such as the use of aminoglycoside antibiotics. The
      challenge of hair cell regeneration is more difficult. Instead of preventing cell
      loss, we must consider methods of stimulating cell division and hair cell
      differentiation from existing cells. We need to know much more about the
      molecular mechanisms that govern these processes so that we can identify
      potential targets for specific drugs or gene therapies. One method of approaching
      the issue is to combine in vitro models of developing hair cells with genomic and
      proteomic technologies. The benefits of hair cell re-growth may not be limited to
      full replacement of pre-existing cells. Surrogate hair cells may help to maintain
      cochlear innervation, even if they do not detect sound, and this property could
      be harnessed to improve the performance of cochlear implants.

PMID- 14662167
TI  - Cochlear implants in children: safety as well as speech and language.
AB  - The development of cochlear implants for children at the University of Melbourne
      and the Bionic Ear Institute, has consisted of a routine of biological and
      engineering safety followed by evaluation of speech processing strategies on
      adults before they are undertaken on children. The initial safety studies were to
      ensure that insertion was atraumatic, the electrical stimulus parameters did not
      lead to loss of ganglion cells and that the electrode could be inserted without
      the risk of middle ear infection leading to meningitis. The initial second
      formant extraction scheme was shown to produce significant open-set speech
      understanding in adults and was approved by the US Food and Drug Administration
      (FDA) in 1985. Following this, an international study was undertaken for the FDA
      on children using a strategy that also included the first formant, and was
      approved in 1990. Additional advances in speech processing have been evaluated on
      adults. However, before using one with high rates of stimulation, it was tested
      for safety on experimental animals. Further advances have been anticipated in
      particular through the development of a peri-modiolar array, the Nucleus Contour.
      Prior to its use on adults, it was tested in the human temporal bone and found to
      lead to minimal trauma. It was evaluated in adults and found to lead to better
      current localization and lower thresholds. A study was undertaken in children
      using a spectral maxima scheme at high rates (advanced combination encoder (ACE))
      and the Contour array as it had given best results in adults. It was approved as
      safe and effective for use in children in 2000. Studies were also undertaken to
      look at plasticity and visual dominance particularly through cognitive studies
      and the use of the McGurk effect. This demonstrated that deaf children with
      implants rely heavily on visual information and there is a great need to have
      unambiguous auditory stimuli to get best results.

PMID- 14662168
TI  - Otorhinolaryngological aspects of handicapped children in visual arts.

PMID- 14662169
TI  - Valedictory--why pediatric otorhinolaryngology is important.
AB  - The importance of the care given by the pediatric otolaryngologist to the
      individual child encompasses the traditional purposes of medicine. This field has
      its special focus on interventions that preserve, restore and/or otherwise
      improve hearing, speech, voice, gustation, olfaction, deglutition, respiration,
      appearances, etc. The value-added dimension of pediatric otolaryngology is of
      essential importance because it enhances communication-language--through the
      vehicles of hearing, voice, and speech. This critical role is manifest in two
      ways. The first relates to the economic bases of society. Comparison of the
      consequences of communications disorders in three different countries ranging,
      currently, from one very highly dependent upon communication skills (The
      Netherlands), to one highly dependent upon communication skills (the United
      States), to a developing nation less dependent upon communication skills (the
      Philippines) is presented. All three nations are adversely affected economically
      and socially by communication disorders. It is estimated that the United States
      loses between 2.5 and 3% of its gross domestic product from the economic sequel
      of communication disorders. It also appears that communication disorders
      contribute to crime, since the prevalence of communication disorders is many
      times greater in populations of juvenile delinquents than in the general
      population. Communication disorders may act synergistically with diminished
      economic and social resources and other factors in the causes of violent behavior
      and crime.

PMID- 14662170
TI  - Effects of otitis media with effusion (OME) on central auditory function.
AB  - Conductive hearing loss attenuates and delays sound passing through the middle
      ear. This impairs binaural hearing and other central auditory functions dependent
      on high fidelity sound transmission. Persistent conductive loss leads to central
      impairments that persist after the peripheral loss has resolved. For example,
      children who have had multiple episodes of otitis media with effusion (OME) in
      the first few years of life may have poor detection of sounds in noisy
      environments, evidenced by reduced binaural unmasking (BU). Recent research shows
      that a 'threshold' level of OME is required to produce impaired BU. Children who
      had OME in one or both ears for more than about 50% of the first 5 years had
      reduced BU. Animal research, using long-term ear plugging, suggests that total
      OME duration, rather than age at the time of having the disease, determines its
      effect on BU. Animals reared with bilateral (but not unilateral) ear plugs also
      have poor auditory temporal resolution, and reduced sensitivity to short tones in
      the presence of background noise, after plug removal. However, given time (6-24
      months) and training, all animals regained normal temporal resolution.

PMID- 14662171
TI  - Immunology of tonsils and adenoids: everything the ENT surgeon needs to know.
AB  - The lymphoid tissue of Waldeyer's ring, and particularly the nasopharyngeal
      tonsil (adenoids), appears to be functionally comparable to nasal-associated
      lymphoid tissue in rodents. Antigen-stimulated lymphoid follicles give rise to:
      (a) clonal B-cell expansion; (b) B-cell receptor affinity maturation; (c)
      positive selection of B cells according to receptor affinity for antigen; (d)
      differentiation to B memory cells and plasma cells; and (e) variable induction of
      the joining (J)-chain gene. B-cell differentiation is also important to promote
      downstream isotype switching of the immunoglobulin (Ig) heavy chain constant
      genes. For tonsillar B cells, this process gives mainly rise to IgG and IgA
      plasma cells, partially associated with J-chain expression. Because the J chain
      is a key peptide in the polymer structure of secretory IgA, tonsils and adenoids
      may provide B cells for mucosal effector sites. Thus, several observations
      suggest that these lymphoid organs generate polymeric IgA (pIgA)-expressing B
      cells that migrate to the upper airway mucosa, lacrimal glands and salivary
      glands. Accordingly, the nasal route of vaccination induces secretory IgA
      dependent regional mucosal immunity and will also enhance systemic immunity.
      Although the pIgA-producing capacity of tonsillar B cells is considerably
      decreased in children with recurrent tonsillitis, a conservative attitude towards
      adenotonsillectomy appears immunologically desirable, particularly in the young
      age group.

PMID- 14662172
TI  - The role of mucosal epithelium in antigen presentation.

PMID- 14662173
TI  - Variant CJD: the present position and future possibilities.
AB  - Variant Creutzfeldt-Jakob disease (CJD) is one of the transmissible spongiform
      encephalopathies (TSEs), or prion diseases, and is thought to be due to
      transmission of BSE from cattle to man via diet. These are characterized by the
      tissue deposition of an abnormal isoform of the normal cellular prion protein, a
      progressive, fatal neurological course and having the potential for infectivity.
      Infectivity is difficult to inactivate, and instances of iatrogenic CJD have been
      reported. The involvement of the tonsil, appendix and other lymphoid tissue in
      variant CJD has increased concerns about possible human-to-human spread.

PMID- 14662174
TI  - HIV infection in children--impact upon ENT doctors.
AB  - The global epidemic of HIV infection remains appalling. By 2001, there were an
      estimated 1.4 million HIV-infected children, with 4.5 million deaths. In the UK,
      paediatric cases are clustered around population centres where there are high
      concentrations of infected immigrant adults, and to a lesser extent, areas where
      IV drug abuse is common. The highest incidence remains in London and the
      southeast. With the national redistribution of immigrant and refugee families,
      any doctor in any specialty may expect to be involved with children who are HIV
      positive, or have clinical AIDS. The majority of children are infected
      vertically, i.e. infection of the infant from an infected mother in the pre-,
      peri-, or post-natal periods. Rates of transmission vary from 15-20% in the
      developed countries. Children with HIV infection may have their primary
      presentation to ENT doctors, who should have appropriate thresholds for
      suspecting the diagnosis. The most common presenting features include persistent
      generalised lymphadenopathy, hepatosplenomegaly, chronic/recurrent diarrhoea,
      poor growth, and fever. Fifteen to twenty percent of untreated children will
      present with an AIDS-defining illness by 12 months, typically with Pneumocystis
      pneumonia at approximately 3-4 months of age. Seventy percent of perinatally
      infected children will exhibit some signs or symptoms by 12 months Without
      treatment, the median age to progression to AIDS is approximately 6 years, and 25
      30% will have died by this age. The median age of death is approximately 9 years.
      Children may also present with repeated/unusual ear infections, sinus disease
      (inc. mastoiditis), tonsillitis, orbital/peri-orbital cellulitis, oral
      candidiasis, and dental infections. Infections with streptococcus pneumoniae and
      group A streptococcus are common, and often progress to severe systemic infection
      with an appreciable mortality. Infections may be due to unusual pathogens such as
      Pseudomonas, 'typical' and atypical Mycobacteria, Candida, Aspergillus, etc.
      Fungal infections of the sinuses (inc. Aspergillus and Rhizopus spp.) may be
      particularly devastating, with rapid spread to involve bone and the central
      nervous system. Another classical presentation, which may present to ENT doctors,
      is that of bilateral parotid enlargement, especially in children who are 'slow
      progressors', many of whom also have Lymphoid Interstitial Pneumonitis (LIP). A
      major attitudinal change has occurred due to advances in 3 main areas: (i) the
      multidisciplinary management of the infected mother (inc. counselling, antenatal
      screening, elective caesarean section, advising against breast feeding, etc.),
      (ii) the prevention of vertical transmission, using anti-retroviral therapy to
      the infected mother during pregnancy, and to the potentially infected infant in
      the first weeks of life, and (iii) major advances due to the advent of highly
      active anti-retroviral treatment. With effective use of these measures,
      transmission rates may be reduced to <2%. None of the measures though, affect a
      cure, and it will still be many years before the development of effective
      vaccines. ENT doctors may be referred children already known to be HIV-positive.
      Knowing how to talk to infected children (and their parents) is full of potential
      pitfalls, and requires careful forethought. Many infection-control policies have
      required considerable rethinking due to the AIDS epidemic. This has especially
      been the case with respect to needle-stick injuries, post-exposure prophylaxis,
      sterilization and re-use of equipment, and safe approaches to surgery.

PMID- 14662175
TI  - Multidisciplinary management of children with craniofacial syndromes with
      particular reference to the airway.

PMID- 14662176
TI  - The role of 24 h pH-recording in pediatric otolaryngologic gastro-esophageal
      reflux disease.
AB  - The purpose of this study was to investigate the role of 24 h pH monitoring for
      the diagnosis of otolaryngologic including rhinologic manifestations of gastro
      esophageal reflux (GER) in children and if possible to correlate the results with
      the efficacy of medical treatment. This is a retrospective study of 72 children
      from January 1997 to December 1999. The children were separated into three groups
      according to the main symptoms (although association of symptoms was frequent):
      rhinologic (n=28), laryngotracheal (n=28) and pharyngeal-otologic (n=16). With
      the classical gastroenterologic criterion (> or =4.2% of total time at pH < 4),
      the pH monitoring was positive in 56% of the patients. However, this criterion
      does not seem to be sensitive for otolaryngologic gastro-esophageal reflux
      disease (GERD) because multiple daytime short reflux episodes are often involved.
      Indeed, the pH monitoring was positive in 75% of the patients (82% in the
      rhinologic group) when a number of 40 episodes in 24h was also taken into
      account. The success rate of medical treatment was about 80% in case of positive
      pH recording. This study underlines that GER is an important factor in pediatric
      otolaryngologic diseases.

PMID- 14662177
TI  - Gastro-oesophageal reflux and feeding: the speech and language therapist's
      perspective.
AB  - Babies and children with gastro-oesophageal reflux often have significant feeding
      difficulties. The symptoms of reflux are described, including the higher risk of
      aspiration. Babies can present with motor and sensory feeding disorders and can
      quickly develop aversive reactions to the feeding process. This effect can be
      long term, and speech and language therapists use various techniques to provide
      babies and young children with positive sensory experiences to reduce the
      aversion and promote successful oral feeding. Advice on grading the introduction
      of textures to the child's diet, messy play and advice on communication and
      interaction will also form part of the feeding plan. The stress on the parents
      will be discussed. Research shows that a truly collaborative multidisciplinary
      approach is likely to be the most successful, encompassing the nutritional,
      medical, psychosocial, and developmental aspects of the child.

PMID- 14662178
TI  - Dysphagia in children: a paediatric surgical perspective.
AB  - Dysphagia in childhood encompasses all disorders of swallowing. The patient
      groups seen frequently in paediatric surgical practice are those with repaired
      oesophageal atresia, some patients with gastro-oesophageal reflux disease and
      those with neurological impairment. Oesophageal atresia patients frequently
      experience dysphagia that is most troublesome in early childhood, fortunately for
      most the long-term outlook is good. Gastro-oesophageal reflux may give rise to
      dysphagia as a result of peptic structure, dysmotility associated with
      oesophagitis or as a complication of anti-reflux surgery. Children with
      neurological impairment and swallowing problems are very difficult for their
      carers to manage. Gastrostomy represents a pragmatic solution to their
      nutritional needs.

PMID- 14662179
TI  - Investigations in paediatric obstructive sleep apnoea: do we need them?
AB  - Ninety percent of normal children with obstructive sleep apnoea (OSA) improve, or
      are cured, with adenotonsillectomy. However, 10% of apparently normal children
      show no improvement following this operation and it has a very poor outcome in
      Down's syndrome, where only about one in six children improve. Adenotonsillectomy
      is also rarely curative in children with cerebral palsy or craniofacial
      syndromes. In these children investigations of the site and severity of their
      obstruction is necessary. Taking a detailed history and asking the parents to
      fill in a questionnaire for data collection will identify most children with OSA.
      Pulse oxymetry has some limitations but is a good screening tool. It does not
      provide enough information for the management of children with complex upper
      airway obstruction who are likely to have on going problems with OSA throughout
      their childhood despite intervention. For these children formal sleep studies are
      needed. Full polysomnography is the gold standard investigation to ascertain the
      severity of OSA. To ascertain the site of upper airway obstruction during sleep,
      sleep nasendoscopy has been found to be an excellent tool. This is performed
      under a light general anaesthetic in main theatres and is demonstrated using
      video footage in the presentation. This is a new classification to document the
      site of airway obstruction in paediatric OSA. A micro-layryngobronchoscopy is
      also required in any child who has daytime noisy breathing, a previous history of
      cardiac malformation or Down's syndrome, in whom a more distal site of airway
      obstruction may be present.

PMID- 14662180
TI  - OSAS in craniofacial syndromes: an unsolved problem.
AB  - Although the incidence of Obstructive Sleep Apnea syndrome (OSAS) in craniofacial
      syndromes is high, it is often not recognized and thus not treated. In order to
      study the diagnostics and treatment options for these patients, we studied a
      group of 72 patients treated in our hospital for Apert, Crouzon, or Pfeiffer
      syndrome, and compared our findings with the literature. There appears to be
      agreement on polysomnography (PSG) and airway endoscopy as the main diagnostic
      options, but therapies are very diverse. Early diagnostics and prompt therapy
      will prevent serious complications.

PMID- 14662181
TI  - Paediatric sleep disorders: the need for multidisciplinary sleep clinics.
AB  - The field of sleep disorders (SD) medicine crosses the boundaries of many medical
      specialties and disciplines. This paper aims to highlight the importance of a
      multidisciplinary approach to the assessment and treatment of SD in children,
      with particular reference to sleep-disordered breathing (SDB). The link between
      SDB and other SD (e.g. various parasomnias, sleep-related anxiety) illustrates
      the need for a holistic approach to assessment since these co-existing SD can be
      the most overt symptoms. Further, different approaches to treatment of the
      various SD are likely to be called for. Multidisciplinary care becomes
      particularly pertinent when dealing with clinical groups of children in which an
      increased prevalence of SD, including SDB, have been noted. Such groups include
      children with intellectual disabilities and those with neurological or
      psychiatric conditions. The nature of their basic condition may make it likely
      that SD will be overlooked with the daytime consequences of the nocturnal
      disturbance (e.g. cognitive/behavioural problems) misattributed to the underlying
      condition. CONCLUSION: An ideal national service would include a limited number
      of specialised sleep centres where a broad and multidisciplinary approach to the
      recognition, assessment and treatment of children's SD was possible.

PMID- 14662182
TI  - Long-term follow-up and mechanisms of obstructive sleep apnea (OSA) and related
      syndromes through infancy and childhood.
AB  - BACKGROUND: Although tonsil and adenoid (T&A) enlargement in children is a
      leading cause of it, Obstructive Sleep Apnea (OSA) may occur at any age. But even
      after T&A surgery, some children experience recurrent apneic episodes. The
      reasons for possible recurrence are unclear. OBJECTIVE: To quantify the
      prevalence of recurrent OSA after T&A surgery and find out a common cause of OSA
      in children from the neonatal period to adulthood. METHOD: A retrospective report
      of apneic patients followed in a tertiary-care center is presented. Telephone
      interviews of parents were performed 3 years after T&A surgery. The questionnaire
      included night and day symptoms related to sleep-disordered breathing (SDB). A
      literature review was performed about associated causes of upper airway stenosis.
      RESULTS: Out of 59 children who were included to follow up, 5 (8.5%) experienced
      residual or recurrent symptoms of SDB. The literature suggests the role of
      skeletal abnormalities in this process through nasal or pharyngeal stenosis.
      Major craniofacial anomalies are a well-known cause of obstruction. Thickened
      soft tissue has to be ruled out. Minor stenoses or neuromuscular disorders are
      less often diagnosed although they seem to be involved as well. CONCLUSION: A
      longitudinal follow-up of apneic children is able to reveal recurrence of SDB
      after adenotonsillectomy and often allows the understanding of mechanisms of
      upstream-induced recurrent pharyngeal obstructions.

PMID- 14662183
TI  - Five children--vignettes of language disorders.
AB  - The pediatric otolaryngologist cares for children who have abnormal language as a
      primary or secondary deficiency. Five children, each with a different form of
      language disorder, are presented. These are children with specific language
      impairment (SLI) expressive, pervasive developmental delay (autism), expressive
      language delay associated with severe to profound hearing loss early in life,
      language delay secondary to a moderate to severe hearing loss diagnosed late and
      not cared for, and language delay secondary delay secondary to social deprivation
      and otitis media with effusion.

PMID- 14662184
TI  - Why did language develop?
AB  - Language developed for communication, to facilitate learning the use of tools and
      weapons, to plan hunting and defence, to develop a "theory of mind" and the tools
      of thought, and to attract and keep a mate. The adaptations required took place
      over many millions of years. The first important one was left-sided
      specialisation of the neural apparatus controlling involuntary emotional
      vocalisations that began more than 200 million years ago. The next was the
      development in primates of "mirror neurones" in the pre-motor cortex some 45
      million years ago. These enabled the imitation and voluntary control of
      previously involuntary manual gestures and vocalisations. The third important
      adaptation was the descent of the larynx, 100,000 years ago, which greatly
      increased the phonological range of vocalisations that could be made. Thus,
      language did not develop all at once as suggested by Chomsky, but evolved
      gradually building upon adaptations originally meeting quite different needs.

PMID- 14662185
TI  - The auditory basis of language impairments: temporal processing versus processing
      efficiency hypotheses.
AB  - Claims have been made that language-impaired children have deficits processing
      rapidly presented or brief sensory information. These claims, known as the
      'temporal processing hypothesis', are supported by demonstrations that language
      impaired children have excess backward masking (BM). One explanation for these
      results is that BM is developmentally delayed in these children. However, little
      was known about how BM normally develops. Recently, we assessed BM in normally
      developing 6- and 8-year-old children and adults. Results showed that BM
      thresholds continue to improve over a comparatively protracted period (>10 years
      old). We also analysed reported deficits in BM in language-impaired and younger
      children, in terms of a model of temporal resolution. This analysis suggests that
      poor processing efficiency, rather than deficits in temporal resolution, can
      account for these results. This 'processing efficiency hypothesis' was recently
      tested in our laboratory. This experiment measured BM as a function of delays
      between the tone and the noise in children and adults. Results supported the
      processing efficiency hypothesis, and suggested that reduced processing
      efficiency alone could account for differences between adults and children. These
      findings provide a new perspective on the mechanisms underlying communication
      disorders, and imply that remediation strategies should be directed towards
      improving processing efficiency, not temporal resolution.

PMID- 14662187
TI  - Language development in autism.
AB  - In this short review article, a summary of the behavioural impairments most
      commonly associated with the spectrum of autism-related disorders is presented,
      with a slightly amplified account of the defining communication impairment. The
      patterns of language ability and disability which typically occur in some forms
      of autism are then outlined, followed by a short section on possible cognitive,
      or psychological, explanations of these patterns. In particular, the hypothesis
      that defective socio-affective and socio-cognitive ('theory of mind') causes
      language impairments, and the hypothesis that temporal processing deficits cause
      these impairments, are outlined and briefly discussed. An extensive list of
      references is included, to support and amplify the summary data included in the
      review.

PMID- 14662188
TI  - The promotion of academic pediatric otolaryngology by journal peer review.
AB  - The professional journal promotes and sustains academic departments through
      several mechanisms that include peer review, editing, timing, and solicitation of
      works. The ways in which peer review strengthens and augments academic pediatric
      otolaryngology are through: the creation of new knowledge; knowledge transfer
      teaching; the establishment and development of quality medical/surgical
      standards; scholarship; and the fostering of the development of the next
      generation of academic physicians is detailed.

PMID- 14662189
TI  - Foreign body injury in children in the twentieth century: a modern comparison to
      the Jackson collection.
AB  - OBJECTIVE: To compare two databases of foreign body (FBs) objects causing injury
      in children (>20 years of age) and record differences in size, shape and material
      for children at risk over a 70-year period of time. STUDY DESIGN: Retrospective
      analysis of the Jackson collection (JC) of FBs (1920-1932) and a 12-year modern
      study (MS) of data taken from 25 children's hospitals in North America over the
      period 1988-2000. Digital images were obtained of the JC collection. METHODS:
      Identify age, sex, and type of products, size, shape, and consistency of material
      from the injury-producing FBs. Statistical Processing for Social Sciences was
      used for analysis of JC versus MS. RESULTS: 5528 children were evaluated from the
      MS, and compared with 1238 from the JC. Boys remain at greater risk than young
      girls (53% versus 47%) over the 70-year period of study. Coins have replaced
      safety pins (31% versus 15%) as the most common offending FBs. Although 99% of
      FBs causing injury are less than 1.25 in. in greatest diameter in both the JC and
      MS, 100% of FBs are eliminated when the test size is greater than 1.75 in.
      CONCLUSIONS: Boys remain at greater risk of injury over the last 60 years.
      However, coins have now emerged as the leading cause of injury in children.
      Children achieve greater protection from risk by modification of the Small Parts
      Test Fixture (SPTF) from 1.25 to 1.75 in. diameter.

PMID- 14662190
TI  - The South African experience with ingestion injury in children.
AB  - INTRODUCTION: The Red Cross Children's Hospital is the only children's hospital
      in South Africa. It has a dedicated trauma unit for all children under the age of
      13 and serves a population of approximately 2 million inhabitants. As part of the
      Child Accident Prevention Foundation program we have kept a database of all
      children treated for trauma in our hospital since 1991. Presently, we have over
      88,000 entries in our database. AIM: To study our experience with ingested
      foreign bodies in children. MATERIALS AND METHODS: A retrospective study was
      performed using the CAPFSA database of a total of 3677 patients presenting with
      foreign bodies. The hospital folders were searched using a standardised data
      extraction form. Only foreign bodies aspirated or ingested were included.
      RESULTS: To date, 241 folders have been analysed. DEMOGRAPHICS: Both sexes were
      equally affected (boys 49%). Age ranged between 0 and 12 years, although there
      was only one child under the age of 1. At the age of 3 years there was a peak in
      incidence (24% of all cases). Nature of ingested object: Although the objects
      were from a range of materials, most were metal (40%) or plastic (23%). The most
      commonly ingested object was a coin (28%), a ball (20%) or bone (8%). The size
      ranged from 0.1 to 3 cm (as measured by virtual ring), the most common size of an
      ingested foreign body was 0.5 cm. Anatomical site: The most common anatomical
      site of impaction was the nose (41%), followed by the oesophagus (20%), the
      stomach (14%) and bowel (11%). Other anatomical sites included hypopharynx,
      nasopharynx, bronchus, larynx and oral cavity. Severity of symptoms: Only 0.4% of
      our cases were assessed as being severe, 14% as moderate, and 44% as mild. Forty
      two percent (42%) had no symptoms. Removal: Fifty-seven percent (57%) of ingested
      foreign bodies were removed surgically, 19% were left in situ, 14% spontaneously
      dislodged and only 1% was removed by Foley catheter manipulation. CONCLUSION: A
      presentation with a foreign body is quite common in our patient population,
      representing approximately 4.2% of all our cases. The majority of ingested
      foreign bodies produced mild or no symptoms, needed surgical removal and had no
      complications.

PMID- 14662191
TI  - Application of data for prevention of foreign body injury in children.
AB  - BACKGROUND: To develop design criteria for consumer products, based on foreign
      body injury and fatality data, to prevent airway obstruction injuries to
      children. METHOD: Beginning in 1988, RAM Consulting has created a worldwide
      database of foreign body injuries. This ongoing project now includes
      approximately 7000 data points from 51 children's hospitals in 15 countries
      located on five continents. Statistical analysis of these data, especially in
      terms of size, shape and consistency of the object and obstruction location and
      severity of injury for the patient has allowed the creation of an injury
      prevention criterion. RESULTS: Analysis of these data reveals that adoption of an
      injury prevention criteria based on the use of a 1.50 in. (38.10 mm) diameter
      gauge for non-spherical objects and a 1.75 in. (44.50 mm) diameter gauge for
      spherical objects would greatly reduce airway obstruction injuries to children.
      Furthermore, the data show that this criterion is independent of country and
      culture. However, the data suggest that a child's exposure to the "mix" of
      objects that may cause airway obstruction varies with the country and culture of
      the child. For example, coins are well represented in the database, however, some
      countries make more coins than other countries and the exposure level may have
      made the difference in the occurrence of incidents. CONCLUSIONS: Airway
      obstruction injuries from consumer products could be greatly decreased by the
      adoption of the presented injury prevention criteria that is founded in a
      statistical analysis of known objects that have caused injury. This criteria is
      dependent on object characteristics and is independent of the country or culture
      of the child.

PMID- 14662192
TI  - The management of congenital tracheal stenosis.
AB  - This paper reviews current concepts and results in the management of congenital
      tracheal stenosis (CTS). Diagnostic options are considered and the requirements
      for successful management defined. Chief amongst these is a multi-disciplinary
      approach with individualised patient management. Severe long-segment CTS
      represents the biggest challenge to clinicians and the worst problems for
      affected families. Near-death episodes are frequent in affected infants and some
      cannot be ventilated and require ECMO. Associated cardiovascular anomalies are
      frequent. Patients require immediate resuscitation and transfer to a specialist
      unit. After careful assessment, accurate diagnosis and discussion, primary
      resection and end-to-end repair with a slide technique should always be the first
      option, with concomitant repair of associated cardiac anomalies. If this is
      impossible because of the severity of the lesion, some form of patch
      tracheoplasty will be indicated. Cardiopulmonary bypass is often required.
      Patches include pericardium, autograft trachea, carotid artery, cartilage, and
      allograft trachea. Mortality ranges from 0 to 30% in the literature, which
      largely comprises single-centre long-term experience. Recurrence is common and
      can be managed by stenting and tracheal homograft implantation. Long-term quality
      of life of survivors is little reported but seems good. Physiological data are
      lacking. To improve results, we suggest a treatment algorithm to rationalise
      care.

PMID- 14662193
TI  - The newborn hearing screening programme in England.
AB  - Following a systematic review of the role of neonatal hearing screening in the
      identification of hearing impaired and deaf children in 1997, the Department of
      Health in England commissioned a national programme of newborn hearing screening
      in 2001 and has linked a systematic evaluation to the first 23 sites in the
      implementation of that policy. It is anticipated that all areas of England will
      participate in the programme by 2004/2005. It is expected that other regions of
      the UK will also aim for implementation by this date. In addition to successful
      advocacy by the two major consumer organisations, there were three key elements
      linked to the decision to implement newborn hearing screening which were
      primarily evidence based and also driven by two significant service developments.
      The evidence base showed that newborn hearing screen was considerably more
      effective and efficient than the infant distraction test used in many areas and
      that there was a high probability that early intervention increased the potential
      for better language and communication. The concern over raised anxiety for those
      parents whose babies need differential assessment as a result of the screen is
      reduced by the low number of referrals and increased efficiency of assessment
      when national protocols are used for screening and assessment. The introduction
      of family friendly hearing services (FFHS) provides a context in which the
      health, education, voluntary and social services can work together to provide an
      equitable and seamless service throughout the year for hearing impaired and deaf
      children and their families. Currently, 22 areas with 110,000 births per annum,
      have been selected for implementation, some of whom use a pilot community-based
      model for screening. A major barrier to rapid progress has been a lack of
      evidence concerning elements of the screening process, e.g. equipment, IT
      systems, training at all levels. It is anticipated that a further 20-40 areas
      with an additional 150,000 birth per annum will be brought into the programme by
      end of 2002/2003. The aims, protocols, training programme and evaluation of the
      NHS Newborn Hearing Screening Programme are presented with a view to highlighting
      the research needed to improve specification of large scale screening programmes.

PMID- 14662194
TI  - The deaf child--challenges in management: a parent's perspective.
AB  - Diana Glover lives in Buckinghamshire, UK with her husband, Ray, and their three
      sons, William (21), Robin (19) and Benjamin (10). Robin and Benjamin are
      profoundly deaf. Ray also has a hearing loss, which is unconnected with the
      children's deafness. Diana is a trustee of the National Deaf Children's Society.
      Diana will compare Robin's experiences with those of Benjamin. She will show how
      difficult it was to obtain a diagnosis of Robin's deafness, in spite of her early
      anxieties about his hearing, and that this had a marked impact on Robin's speech
      and language acquisition. She will speak about the struggle she and Ray had to
      convince their Local Education Authority that Robin should move from mainstream
      schooling to a boarding school for the deaf at the age of 9. She will also
      express her current anxieties as Robin, who has only deaf friends, moves from
      Mary Hare Grammar School for the Deaf to mainstream Higher Education. Robin's
      experiences will be contrasted with Benjamin's diagnosis at 7 weeks and progress
      in mainstream education. Diana will also highlight some of the issues that she
      and Ray had to consider when they agreed that Benjamin should have a cochlear
      implant at the age of 2. It will be demonstrated that having one hearing and two
      deaf sons has a profound effect on relationships within the family and with
      professionals. Diana will show how she and Ray have learned that one can easily
      overlook the needs of a hearing sibling, and that it is equally important for
      deaf children to come to terms with their disability. She will summarise the
      difficult choices they have had to make over implantation, communication methods
      and schooling and demonstrate that, even within one family, the needs of deaf
      children are never the same.

PMID- 14662195
TI  - Recent advances in the treatment of rhinitis and rhinosinusitis.
AB  - Current rhinitis treatment is unsatisfactory for many patients, possibly because
      monotherapy is employed, without regard to the major presenting symptom.
      Recognition of the impact of rhinitis on quality of life and on associated
      disorders such as asthma has led to the development of guidelines, use of which
      has been shown to improve symptom control and quality of life compared to
      unguided therapy. The role of antihistamines, topical corticosteroids and anti
      leukotrienes is discussed.

PMID- 14662196
TI  - Evaluation of CD25, CD152, Fas-ligand expression in the adenoids of allergic and
      non-allergic children: a pilot study.
AB  - BACKGROUND: The nasal mucosa is the initial site in the upper airways of the host
      defence against antigen challenge. The lymphatic structure closest to the nasal
      mucosa is the adenoid. Apoptotic cell death is an important mechanism for
      maintaining homeostasis in the immune system, and for regulating the fates of
      lymphocytes following encounters with self and foreign antigens. This process
      regulates the population of lymphocytes in peripheral lymphoid organs following
      exposure to various allergens. OBJECTIVES: The objectives of this study were to
      find evidence for the hypothesis that the development of allergic illness depends
      on allergic sensitisation in the adenoid. METHODS: In this study, cellular
      infiltrates in the adenoids of 12 allergic and 13 non-allergic children were
      evaluated. The number of positive cells for CD4, CD8, CD25, CD152, and Fas-ligand
      were determined using immunohistochemical stainings and imaging analysis
      techniques. RESULTS: There was found a higher expression of CD25, CD152 and Fas
      ligand in small, activated lymphocytes, especially in the interfollicular area of
      allergic patients than in the control group. The expression of FasL in activated
      lymphocytes, as well as in macrophages, was observed. Statistical analysis has
      shown a significant correlation between expression of CD152 and allergic disease,
      and a more intense correlation between CD25, CD152 and Fas-ligand and allergic
      disease. There was no statistically important divergence in the CD4/CD8 ratio in
      different samples.

PMID- 14662197
TI  - Pediatric endoscopic sinus surgery--does it have a future?

PMID- 14662198
TI  - Is there a future for pediatric sinus surgery? An American perspective.
AB  - The role of pediatric sinus surgery in chronic sinusitis continues to evolve. By
      the early 1990s, endoscopic sinus surgery was being touted as a primary
      intervention of chronic pediatric sinusitis. Around this same time these
      endoscopic techniques were being attempted in congenital nasosinus malformations,
      acute orbital complications of sinusitis and other areas. In 1996 the Brussels
      consensus paper on pediatric sinusitis recommended that the latter set of nasal
      disorders were "absolute" indications, and ironically, chronic sinusitis was a
      "possible indication". This report reviews some of the changes which have
      impacted the use of sinus surgery during the last decade including the perception
      of nasal symptoms during the era of antibiotic resistance in bacteria, improved
      instrumentation, the role of adenoidectomy, research on the effects of sinus
      surgery on facial growth, and the research on surgical outcomes.

PMID- 14662199
TI  - The influence of long-term tracheostomy on speech and language development in
      children.
AB  - BACKGROUND: Individuals diagnosed as having primary neurological disorders have a
      high incidence of abnormal speech and language development. However, results in
      cohorts where this group are excluded are controversial. With no coexisting
      neurological impairment, some suggested that tracheostomy has little influence on
      speech development, whilst others showed a clear pattern of language disability.
      The aim of this study is to evaluate the influence of tracheostomy on speech and
      language development. METHOD: Retrospective study using standardised outcome
      measures. RESULTS: A series of 39 paediatric tracheostomies was studied. In the
      group where children had neurological disorders, 94% showed no language or
      delayed language development. In contrast, of the group of children without a
      neurological impairment, 60.9% had normal speech and language development. The
      median age at the decannulation in those children with delayed speech was 23
      months, whilst in those children with normal speech it was 14.5 months.
      CONCLUSION: Tracheostomy affects speech and language development in those with
      and without neurological disorders. Crucial factors affecting speech and language
      development within the neurologically normal group are age at the tracheostomy,
      and the duration of the tracheostomy until decannulation. Achieving earliest
      decannulation improves the chance of a normal speech and language development.

PMID- 14662200
TI  - Effect of disposable instruments on paediatric post-tonsillectomy haemorrhage
      rates.
AB  - BACKGROUND: A government directive aiming to minimise the theoretical risk of
      acquiring variant Creutzfeld-Jacob disease from reusable instruments lead to
      tonsillectomy with disposable instruments becoming standard practice in the UK
      during 2001. A perceived increase in post-tonsillectomy haemorrhage followed soon
      after implementation of the directive. OBJECTIVE: To determine if the
      introduction of disposable instruments is associated with a statistically
      significant change in post-tonsillectomy haemorrhage rates in children. METHODS:
      A prospective audit of paediatric tonsillectomy with reusable instruments (n=156)
      had been undertaken (November 1999-November 2000). All children undergoing
      tonsillectomy with disposable instruments (n=115) were also studied prospectively
      (August 2001-December 2001) allowing the reactionary and secondary post
      tonsillectomy haemorrhage rates for the two study periods to be compared. We
      hypothesised no difference in haemorrhage rates between reusable and disposable
      instruments. Statistical significance was calculated using Fisher's exact test
      and confidence intervals were established for the differences between study
      groups. RESULTS: Cold dissection was undertaken in 62 children with reusable
      instruments and in 76 children with disposable instruments with secondary
      haemorrhage rates of 3.2% (n=2) and 2.6% (n=2), respectively. Bipolar diathermy
      dissection was undertaken in 94 children with reusable instruments and in 39
      children with disposable instruments with respective secondary haemorrhage rates
      of 6.4% (n=6) and 12.8% (n=5). No reactionary haemorrhages occurred with reusable
      or disposable instruments. No difference was found in the overall secondary
      haemorrhage rate between reusable and disposable instruments (P=0.93, difference
      1.0% (95% CI; -7.4 to +4.6)). CONCLUSIONS: The introduction of disposable
      instruments has not produced a statistically significant increase in paediatric
      post-tonsillectomy haemorrhage rates in our centre.

PMID- 14662201
TI  - Efficacy of cefpodoxime in the prophylaxis of recurrent pharyngotonsillitis.
AB  - BACKGROUND: Recurrent acute pharyngotonsillitis remains a common illness in
      children and young adults and can lead to serious complications if not treated.
      cefpodoxime proxetil is a second-generation oral cephalosporin, which shows
      potent antibacterial activity against both Gram-positive and Gram-negative
      bacteria and high stability in the presence of beta-lactamases. OBJECTIVE: We
      aimed to evaluate the efficacy of second-generation cephalosporins in the
      prophylaxis of recurrent pharyngotonsillitis in children. METHODS: A total of 180
      children aged between 4 and 14 years with recurrent pharyngotonsillitis were
      randomized to receive either cefpodoxime proxetil (100 mg twice a day, 6 days a
      month for 6 months) or placebo (at the same dosage). RESULTS AND CONCLUSIONS: Our
      results show that treatment with cefpodoxime proxetil may be effective in
      reducing symptoms of recurrent pharyngotonsillitis and preventing recurrences
      without causing side effects or developing bacterial resistance.

PMID- 14662202
TI  - OSAS in children.
AB  - BACKGROUND: Major risk factors for obstructive sleep apnea syndrome (OSAS) in
      children include adenotonsillar hypertrophy, neuromuscular disease and syndromes
      such as Down's or Pierre-Robin's syndrome; there is currently no consensus
      concerning diagnosis and therapy. METHODS: The study analyses 40 children, aged 2
      through 14 years, with macroscopic tonsillar hypertrophy (without recurrent
      tonsillitis but with OSAS) underwent adenotonsillectomy. Parents were invited to
      indicate the intensity of their children's symptomatology using a subjective
      evaluation scale, each patient underwent cephalometric analysis and
      polysomnography (PSG) before and after surgery. RESULTS: The subjective scale of
      symptoms passed from 3.01 before treatment to 0.42 after treatment,
      rhinomanometry, passed from 3.456 to 0.896 p after 1 month the surgical operation
      (P<0.05). The polysomnography showed a resolution of the number of obstructive
      events in 37 patients and a reduction in 3 patients and RDI index fell from a
      mean of 26.9-2.6 after therapy. The average of oxygen saturation changed from 79%
      before treatment to 95% after therapy. CONCLUSIONS: Adenotonsillectomy plays a
      major role in the treatment of OSAS.

PMID- 14662203
TI  - Aseptic surgical technique and postgrommet otorrhoea.
AB  - Myringotomy and grommet insertion is one of the most common operations performed
      in Europe today, with an estimated 70,000 being carried out annually in Britain
      alone [Lancet 1 (1984) 835]. Otorrhoea is a common postoperative complication.
      There is controversy about the degree to which surgical asepsis should be
      maintained during the operation. This prospective study of 35 patients (70 ears)
      undergoing grommet insertion was carried out to evaluate the efficacy of two
      differing degrees of surgical asepsis. Using each patient as their own control a
      grommet was inserted into one ear with the surgeon wearing sterile gloves and
      masks, and the other wearing only clean non-sterile gloves. Discharge in the
      first 14 days occurred in five ears, three cases belonging to the former group
      and two to the latter. The results indicate that there is no significant
      difference in the incidence of postoperative otorrhoea using either of the above
      methods, and demonstrate that this operation may be performed in a safe but more
      cost-efficient manner.

PMID- 14662206
TI  - An opportunity for professionalism in the Match.

PMID- 14662207
TI  - Commentary on "Human papillomavirus infection of the cervix: relative risk
      association of 15 common anogenital types".

PMID- 14662208
TI  - Effect of the Women's Health Initiative on women's decisions to discontinue
      postmenopausal hormone therapy.
AB  - OBJECTIVE: To examine whether women who were using postmenopausal hormone therapy
      (HT) before publication of Women's Health Initiative findings about risks
      associated with HT had been informed about the findings once published; and to
      estimate how knowledge of these findings was associated with their decision to
      discontinue HT. METHODS: We performed a telephone survey of 670 female members of
      a large health maintenance organization, aged 50-69 yr, who had regularly used HT
      from July 1, 2001, through June 30, 2002. RESULTS: Most women (93%) reported
      hearing about the new findings; however, only 57% considered the quality of this
      information to be good, regardless of its source: mass media (21%), the health
      plan (32%), or a health care practitioner (34%). Women's knowledge of Women's
      Health Initiative findings was generally poor; 64% did not know what the findings
      were, 7% were unsure of their knowledge, 6% had incorrect knowledge, and 23% had
      correct knowledge of Women's Health Initiative findings. On a simple, five
      question, true-or-false quiz about HT risks, 30% of respondents answered four to
      five questions correctly. Although not well informed, 56% reported attempting to
      discontinue HT in the 6 to 8 months after July 2002. Our multivariable model
      included five statistically significant predictors of attempting to stop HT:
      having been sent a letter about Women's Health Initiative findings (odds ratio
      [OR] 2.7; 95% confidence interval [CI] 1.8, 3.9), reporting good-quality
      information from media (OR 2.1; 95% CI 1.3, 3.3), having started HT for health
      promotion (OR 2.0; 95% CI 1.2, 3.3), using a lower-than-standard dosage of
      estrogen (OR 1.9; 95% CI 1.1, 3.1), and correctly answering four or more items on
      the HT quiz (OR 1.9; 95% CI 1.2, 2.8). CONCLUSION: During the 6-8 months after
      publication of Women's Health Initiative trial findings, most regular
      postmenopausal HT users tried to stop using HT, despite not being well informed
      about the Women's Health Initiative findings.

PMID- 14662209
TI  - Predictors of difficulty when discontinuing postmenopausal hormone therapy.
AB  - OBJECTIVE: To describe the experiences of postmenopausal women who try to stop
      hormone therapy and to identify characteristics associated with inability to
      stop. METHODS: We conducted telephone interviews with 377 randomly selected
      female members of the Kaiser Foundation Health Plan, aged 50-69 years, who
      regularly used hormone therapy for at least 1 year before July 1, 2002 and had
      attempted to stop between July 2002 and March 2003. RESULTS: Of the 377 women,
      280 (74%) successfully stopped and 97 (26%) resumed taking hormone therapy. The
      major predictor of resuming hormone therapy use was the development of
      troublesome withdrawal symptoms (odds ratio 8.8; 95% confidence interval 4.9,
      16.0). Report of hysterectomy, hormone therapy prescribed by a nongynecologist,
      and perception of high risk of hip or spine fracture were independently
      associated with a higher likelihood of unsuccessful stopping. Women with a
      hysterectomy who had used hormone therapy for 10 or more years and who started
      hormone therapy mainly for reasons other than health promotion were more likely
      (P <.001) to be unsuccessful in quitting (44%) compared with those with one or
      two (25%) or none (9%) of these three characteristics. Most successful stoppers
      (71%) stopped hormone therapy abruptly, but 29% tapered off hormone therapy;
      there was no difference in the incidence of troublesome withdrawal symptoms or
      successful quitting between these two groups. CONCLUSION: Approximately one
      quarter of women who try to stop report that they are unable to discontinue
      postmenopausal hormone therapy, primarily because they develop troublesome
      withdrawal symptoms. Effective approaches to reducing hormone therapy withdrawal
      symptoms should be a priority for future research.

PMID- 14662210
TI  - Prevalence of estrogen or estrogen-progestin hormone therapy use.
AB  - OBJECTIVE: To use nationally representative data to produce prevalence estimates
      of combination estrogen-progestin therapy and estrogen-only therapy by
      covariates, and to evaluate differences between current use of short duration
      (less than 5 years) and current long-term use. METHODS: We analyzed data from
      female respondents 40 years of age and older (n = 9400) who were interviewed in
      the 1999 National Health Interview Survey. Hormone therapy use was categorized
      into four types: current estrogen-progestin therapy use, current estrogen-only
      therapy use, former hormone therapy use, and never use. We calculated the
      prevalence of hormone therapy by different levels of previously identified
      covariates of hormone therapy, as well as overall prevalence of hormone therapy
      use by length of use. RESULTS: Approximately 24% of women aged 40 years or older
      were current hormone users. Of these, 30% were taking estrogen-progestin therapy,
      and 70% were taking estrogen-only therapy. The prevalence of hormone use differed
      dramatically by hysterectomy status and age, and less so by many demographic,
      health-risk behavior, medical access, and medical history variables. Among women
      with no hysterectomy, the associations with many of the covariates were stronger
      for estrogen-progestin therapy use than for estrogen-only therapy use. Only 3% of
      women were estimated to be current estrogen-progestin therapy users for 5 or more
      years, whereas 10% were current estrogen-only therapy users for 5 or more years.
      CONCLUSION: Although many women at midlife and older were current hormone users,
      very few were long-term users of estrogen-progestin therapy.

PMID- 14662211
TI  - A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to
      pregnancy.
AB  - OBJECTIVE: Hyperemesis gravidarum, a severe form of nausea and vomiting due to
      pregnancy for which there is no proven pharmacological treatment, is the third
      leading cause for hospitalization during pregnancy. Corticosteroids are commonly
      used for the treatment of nausea and vomiting due to cancer chemotherapy-induced
      emesis and might prove useful in hyperemesis gravidarum. METHODS: A randomized,
      double-blind, placebo-controlled trial was conducted in 126 women who previously
      had not responded to outpatient therapy for hyperemesis gravidarum during the
      first half of pregnancy. Intravenous methylprednisolone (125 mg) was followed by
      an oral prednisone taper (40 mg for 1 day, 20 mg for 3 days, 10 mg for 3 days, 5
      mg for 7 days) versus an identical-appearing placebo regimen. All women also
      received promethazine 25 mg and metoclopramide 10 mg intravenously every 6 hours
      for 24 hours, followed by the same regimen administered orally as needed until
      discharge. The primary study outcome was the number of women requiring
      rehospitalization for hyperemesis gravidarum. RESULTS: A total of 110 women
      delivered at our hospital and had pregnancy outcomes available for analysis; 56
      were randomized to corticosteroids and 54 were administered placebo. Nineteen
      women in each study group required rehospitalization (34% versus 35%, P =.89, for
      corticosteroids versus placebo, respectively). CONCLUSION: The addition of
      parenteral and oral corticosteroids to the treatment of women with hyperemesis
      gravidarum did not reduce the need for rehospitalization later in pregnancy.

PMID- 14662212
TI  - Periconceptional multivitamin supplementation and multimalformed offspring.
AB  - OBJECTIVE: To study the human teratogenic risk of a folic acid-containing
      multivitamin. METHODS: We evaluated the data set of two Hungarian intervention
      studies: a randomized double-blind, controlled trial and a two-cohort, controlled
      study of the same folic acid-containing multivitamin in participants of the
      Hungarian periconceptional service. RESULTS: Of 2471 supplemented and 2391
      unsupplemented women, 18 and 21, respectively, had multiple congenital
      abnormalities in the randomized, controlled trial. Of 3056 supplemented and
      unsupplemented pairs in the two-cohort, controlled study, 33 and 32,
      respectively, were affected with multiple congenital abnormalities. After the
      combination of two data sets, the number of cases with multiple congenital
      abnormalities was 51 in the supplemented group and 53 in the unsupplemented group
      (odds ratio 0.89; 95% confidence interval 0.45, 1.68). In addition, there was no
      difference in the occurrence of specified multiple congenital abnormality
      entities or of unidentified multimalformed informative offspring. CONCLUSION: We
      found no evidence that periconceptional folic acid-containing multivitamin
      supplementation either prevents or induces multiple congenital abnormalities.

PMID- 14662213
TI  - Racial disparity in meconium-stained amniotic fluid and meconium aspiration
      syndrome in the United States, 1989-2000.
AB  - OBJECTIVE: To estimate the prevalence of meconium-stained amniotic fluid and
      meconium aspiration syndrome, as well as the differences in case fatality from
      meconium aspiration syndrome, between non-Hispanic black and non-Hispanic white
      infants. METHODS: We studied non-Hispanic black and non-Hispanic white live
      births with weights greater than 2.5 kg and gestational ages greater than 35
      weeks, using the linked US birth and infant death cohorts for three periods: 1989
      1991, 1995-1997, and 1998-2000. We used logistic regression to estimate the risks
      of meconium-stained amniotic fluid and meconium aspiration syndrome and to
      estimate the case fatality of meconium aspiration syndrome by maternal race,
      birth weight, period, and pregnancy complications. RESULTS: Risk of meconium
      stained amniotic fluid was 80% higher in non-Hispanic blacks when compared with
      non-Hispanic whites (birth weight-adjusted odds ratio [OR], 1.81, 95% confidence
      interval [CI] 1.80, 1.82). The prevalence of pregnancy complications did not
      explain this racial disparity. Risk of meconium aspiration syndrome in non
      Hispanic blacks was 67% higher when compared with non-Hispanic whites (birth
      weight-adjusted OR 1.67, 95% CI 1.64, 1.70). The case fatality rate of meconium
      aspiration syndrome was similar between non-Hispanic blacks and non-Hispanic
      whites in the three periods, with rates of 15.5, 15.2, and 11.2 per 1000 in non
      Hispanic blacks and 13.5, 11.2, and 10.1 per 1000 in non-Hispanic whites in 1989
      1991, 1995-1997, and 1998-2000, respectively. CONCLUSION: Our results suggest
      that when compared with non-Hispanic whites, non-Hispanic blacks are at
      significantly greater risk for meconium-stained amniotic fluid and meconium
      aspiration syndrome but not for meconium aspiration syndrome case fatality.

PMID- 14662214
TI  - Association between promyelocyte protein and small ubiquitin-like modifier
      protein and the progression of cervical neoplasia.
AB  - OBJECTIVE: To examine the association between the size and number of promyelocyte
      protein-containing nuclear bodies, their colocalization with the small ubiquitin
      like modifier protein, and existing histopathologic staging of cervical neoplasia
      progressing toward squamous cell carcinoma. METHODS: Fluorescence-based
      immunodetection of the promyelocyte protein and the small ubiquitin-like modifier
      protein was performed on paraffin-embedded and histopathologically graded human
      uterine cervical tissues. Quantitative measurements of the size and number of the
      promyelocyte protein-containing nuclear bodies were made and statistically
      analyzed. RESULTS: We found that promyelocyte protein-containing nuclear bodies
      exhibit changes in both size and number throughout the continuum of cervical
      intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. An increase
      in number and size of the bodies occurs with progression from normal to CIN I/CIN
      II. In CIN III, two new subcategories of nuclear body are present with distinctly
      different promyelocyte protein patterns, with the type B CIN III losing the small
      ubiquitin-like modifier protein partnership. In squamous cell carcinoma, we see
      the loss of this colocalization in both well and poorly differentiated tumors,
      with a distinctly different promyelocyte protein pattern. Well-differentiated
      tumors have bigger nuclear bodies that are more numerous than those of the poorly
      differentiated tumors. CONCLUSION: These data support the use of promyelocyte and
      small ubiquitin-like modifier proteins as a cytodiagnostic marker that parallels
      cervical cancer progression.

PMID- 14662215
TI  - Complications associated with global endometrial ablation: the utility of the
      MAUDE database.
AB  - OBJECTIVE: To investigate the number and type of complications associated with
      global endometrial ablation using public-access governmental databanks. METHODS:
      MEDLINE (PubMed) and the US Food and Drug Administration Manufacturer and User
      Facility Device Experience (MAUDE) databases were searched for entries for the
      four US Food and Drug Administration-approved global endometrial ablation
      devices. RESULTS: Traditional MEDLINE and bibliography searches yielded reports
      of two cases of hemorrhage, one case of pelvic inflammatory disease, 20 cases of
      endometritis, two cases of first-degree skin burns, nine cases of hematometra,
      and 16 cases of vaginitis and/or cystitis. A search of the US Food and Drug
      Administration MAUDE database yielded reports of 85 complications in 62 patients.
      These included major complications: eight cases of thermal bowel injury, 30 cases
      of uterine perforation, 12 cases in which emergent laparotomy was required, and
      three intensive care unit admissions. One patient developed necrotizing fasciitis
      and eventually underwent vulvectomy, ureterocutaneous ostomy, and bilateral below
      the-knee amputations. One of the patients with thermal injury to the bowel died.
      CONCLUSION: Use of the US Food and Drug Administration MAUDE database is helpful
      in identifying serious complications associated with global endometrial ablation
      not yet reported in the medical literature.

PMID- 14662216
TI  - Architectural differences in the bony pelvis of women with and without pelvic
      floor disorders.
AB  - OBJECTIVE: To investigate the hypothesis that the architecture of the bony pelvis
      differs between women with and without pelvic floor disorders. METHODS: We
      designed a case-control study of women who had undergone magnetic resonance
      imaging (MRI) of the pelvis at our institution. Records were reviewed to identify
      women with and without pelvic floor disorders (urinary or anal incontinence,
      other symptoms of urinary tract dysfunction, or pelvic organ prolapse).
      Pelvimetry techniques were standardized. Relevant measures included transverse
      diameter of the inlet, angle of the pubic arch, intertuberous diameter,
      interspinous diameter, sacrococcygeal length, depth of sacral curvature,
      anteroposterior conjugate, obstetrical conjugate, and anteroposterior outlet.
      Multiple logistic regression analysis was used to identify women with pelvic
      floor disorders as a function of their pelvic dimensions, controlling for
      potentially confounding variables. RESULTS: Subjects included 59 women with
      pelvic floor disorders and 39 women without pelvic floor disorders. Women with
      pelvic floor disorders had a wider transverse inlet, wider intertuberous
      diameter, wider interspinous diameter, greater sacrococcygeal length, deeper
      sacral curvature, and narrower anteroposterior outlet. When controlling for the
      confounding effects of age, race, and parity, we found that a wider transverse
      inlet (odds ratio 3.425) and a shorter obstetrical conjugate (odds ratio 0.233)
      were significantly associated with pelvic floor disorders. CONCLUSION: A wide
      transverse inlet and narrow obstetrical conjugate are associated with pelvic
      floor disorders. We speculate that these features of bony pelvic architecture may
      predispose the patient to neuromuscular and connective tissue injuries, leading
      to the development of pelvic floor disorders.

PMID- 14662217
TI  - Urinary incontinence in the 12-month postpartum period.
AB  - OBJECTIVE: To describe the prevalence and severity of urinary incontinence in the
      12-month postpartum period and to relate this incontinence to several potential
      risk factors including body mass index, smoking, oral contraceptives, breast
      feeding, and pelvic floor muscle exercise. METHODS: Participants were 523 women,
      aged 14 to 42 years, who had obstetrical deliveries. The women were interviewed
      in their rooms on postpartum day 2 or 3 and by telephone 6 weeks, 3 months, 6
      months, and 12 months postpartum. Chart abstraction was conducted to obtain
      obstetrical data from the index delivery. RESULTS: At 6 weeks postpartum, 11.36%
      of women reported some degree of urinary incontinence since the index delivery.
      Although the rate of incontinence did not change significantly over the
      postpartum year, frequency of accidents decreased over time. In the generalized
      estimating equation, postpartum incontinence was significantly associated with
      seven variables: baseline report of smoking (odds ratio [OR] 2.934; P =.002),
      incontinence during pregnancy (OR 2.002; P =.007), length of breast-feeding (OR
      1.169; P =.023), vaginal delivery (OR 2.360; P =.002), use of forceps (OR 1.870;
      P =.024), and two time-varying covariates: frequency of urination (OR 1.123; P =
      <.001) and body mass index (OR 1.055; P =.005). Factors not associated with
      postpartum incontinence included age, race, education, episiotomy, number of
      vaginal deliveries, attendance at childbirth preparation classes, and performing
      pelvic floor muscle exercises during the postpartum period. CONCLUSION:
      Postpartum incontinence is associated with several risk factors, some of which
      are potentially modifiable and others that can help target at-risk women for
      early intervention.

PMID- 14662218
TI  - Fecal incontinence after high-risk delivery.
AB  - OBJECTIVE: To investigate the prevalence of and factors associated with fecal
      incontinence and its precursors among high-risk women at 12 months postpartum.
      METHODS: A survey of women in the immediate and later postpartum was conducted.
      Participants were 568 women at higher risk of anal sphincter damage, namely those
      who had an instrumental delivery and/or delivered a high birth weight infant
      (4000 g or more) at tertiary teaching hospitals in Australia. Women participated
      in a baseline hospital-based interview and a 12-month follow-up telephone
      interview. The main outcome measures were frank fecal incontinence (solid and/or
      liquid stool) and precursor symptoms (flatal incontinence, soiling, and/or fecal
      urgency) at 12 months postpartum. RESULTS: Prevalence rates were 2.6% for solid
      stool incontinence and 4.9% for liquid stool incontinence. Overall, 6.9% women
      had either one or both of these symptoms of frank fecal incontinence. Prevalence
      rates were 24.4% for flatal incontinence, 10.9% for soiling, and 14.8% for fecal
      urgency. Overall, 32.4% women had at least one of these precurser symptoms.
      Concurrent urinary incontinence and postpartum constipation were significantly
      associated with both frank fecal incontinence and precursor symptoms. In
      addition, joint hypermobility and older maternal age were associated with frank
      fecal incontinence, whereas inability to stop the urine flow and multiparity was
      associated with precursor symptoms. CONCLUSION: The present findings suggest that
      older and multiparous women, and women with joint hypermobility are at increased
      risk of postpartum anal incontinence symptoms after a high-risk delivery.
      Concurrent urinary incontinence, flow-stopping inability, and constipation are
      also associated with postpartum anal incontinence symptoms after high-risk
      deliveries.

PMID- 14662219
TI  - Suicide in pregnancy.
AB  - BACKGROUND: Pregnant women with bipolar disorder often elicit conflicts between
      maternal and fetal considerations. CASE: A 26-year-old primigravida at 12 weeks'
      gestation presented for emergency psychiatric evaluation after discontinuing
      psychotropic medications when starting prenatal care. She developed worsening
      depression and was suicidal. She was admitted to an inpatient psychiatric unit,
      medication was reinitiated, and she appeared to stabilize well enough to be
      followed as an outpatient. Two days after discharge, she shot herself in the left
      chest, resulting in her death and that of her fetus. CONCLUSION: When choosing to
      maintain or discontinue mood stabilizers during pregnancy, decisions are best
      made by the use of a risk-benefit model that takes into account the health and
      well-being of both mother and fetus.

PMID- 14662220
TI  - Reproductive correlates of depressive symptoms among low-income minority women.
AB  - OBJECTIVE: To estimate the prevalence of depressive symptoms among women of
      reproductive age attending family planning clinics across southeast Texas in
      addition to demographic and reproductive characteristics associated with these
      symptoms. METHODS: A retrospective, self-reported, paper-and-pencil survey
      designed to assess health and risk behaviors was administered to 4726 low-income
      suburban women, aged 12 and 40 years, attending a family planning clinic in
      southeast Texas. The survey contained a background and demographic section in
      addition to six sections addressing health risk behaviors. Women also completed
      the 13-item Beck Depression Inventory to assess depressive symptoms. RESULTS: A
      total of 11.8% exhibited mild symptoms of depression, 14.0% had moderate
      symptoms, and 4.8% had severe symptoms. Women were at increased risk of moderate
      to severe symptoms of depression if they were Hispanic, had not graduated high
      school, were unemployed, or currently smoked cigarettes. Sexual or reproductive
      characteristics associated with moderate to severe symptoms included two or more
      lifetime sexual partners, having used hormonal contraception before age 13, not
      using any birth control at last intercourse, having had a sexually transmitted
      disease, not having had sexual intercourse in the last 3 months or having had it
      under the influence of alcohol or drugs, and having heard a family member worry
      about contracting a sexually transmitted disease or discuss use of alcohol or
      drugs before sex. CONCLUSION: A large percentage of women experience moderate to
      severe depressive symptoms during their reproductive years. These symptoms are
      associated with numerous risk behaviors, including inconsistent use of birth
      control. Women's health care providers have the opportunity to provide a valuable
      service by screening for depressive symptoms.

PMID- 14662221
TI  - Postnatal depression and sexual health after childbirth.
AB  - OBJECTIVE: To investigate the sexual health experiences of depressed and
      nondepressed postnatal women within a 6-month postnatal period. METHODS: This
      cross-sectional study used obstetric records and postal survey 6 months after
      delivery from a cohort of primiparous women (n = 796) delivering a live-born
      infant at St. George's NHS Trust, London. Women self-reported sexual problems and
      sexual behaviors and completed the Edinburgh Postnatal Depression Scale. RESULTS:
      Of the 796 parturients, 484 responded (61%), and 468 completed the survey
      questions on depression and sexual health (97%). Of the latter, 57 (12%) fit the
      Edinburgh Postnatal Depression Scale criteria. Comparing the depressed with
      nondepressed women, resumption of sexual activity occurred with 77% versus 90% (P
      =.003), and the median number of specific sexual problems reported was two versus
      one, respectively (P =.009). CONCLUSION: Sexual health problems were common after
      childbirth in both depressed and nondepressed women; however, depressed women
      were less likely to have resumed intercourse at 6 months and more likely to
      report sexual health problems. Given the frequency of sexual health problems,
      postnatal sexual morbidity cannot be assumed to be simply a product of the
      depressed mental state.

PMID- 14662222
TI  - Pregnancy-related mortality due to cardiomyopathy: United States, 1991-1997.
AB  - OBJECTIVE: To describe characteristics and risk factors for pregnancy-related
      deaths due to cardiomyopathy during 1991-1997 and to assess reasons for the
      increasing trend in reporting of pregnancy-related deaths due to cardiomyopathy
      from 1979 through 1997. METHODS: We used data from the Centers for Disease
      Control (CDC) and Prevention's Pregnancy Mortality Surveillance System to examine
      pregnancy-related deaths due to cardiomyopathy from 1991 through 1997. The
      pregnancy-related mortality ratio for cardiomyopathy was defined as the number of
      pregnancy-related deaths from cardiomyopathy per 100,000 live births.
      Cardiomyopathy was classified as peripartum cardiomyopathy or cardiomyopathy due
      to other causes. RESULTS: Of the 245 cardiomyopathy deaths that occurred during
      1991-1997, 171 (70%) were due to peripartum cardiomyopathy. The cause-specific
      pregnancy-related mortality ratio was 0.88 per 100,000 live births. Mortality
      increased as maternal age increased. Black women were 6.4 times as likely to die
      from cardiomyopathy as white women. Among peripartum cardiomyopathy cases in
      which the interval from the end of pregnancy was known, 2% died undelivered, 48%
      died within 42 days of delivery, and 50% died between 43 days and 1 year
      postpartum. CONCLUSION: Cardiomyopathy accounts for an increasing proportion of
      reported pregnancy-related deaths, and the more than six-fold excess risk of
      death from cardiomyopathy among black women is larger than that for any other
      cause of death. The increased reporting of these deaths might be largely due to
      improved case ascertainment. Further studies are required to estimate the
      prevalence of cardiomyopathy and identify modifiable risk factors associated with
      these deaths and the reasons for this racial disparity.

PMID- 14662223
TI  - The use of a continuous infusion of epinephrine for anaphylactic shock during
      labor.
AB  - BACKGROUND: Anaphylaxis is a potentially life threatening, acute, and severe
      systemic reaction that occurs after the reexposure to a specific antigen. This
      immunoglobulin E-mediated process is the result of the action of basophils and
      mast cell mediators, causing severe brochospasm, laringospasm, angioedema,
      urticaria, and cardiovascular collapse. CASE: We present a case of anaphylactic
      shock during labor secondary to administration of ampicillin for group B
      streptococcus prophylaxis. Generalized itching and hives were soon followed by
      severe maternal hypotension and tachycardia and prolonged fetal bradycardia.
      These symptoms responded partially to the administration of fluids and parenteral
      epinephrine. A continuous infusion of epinephrine was required for persistent
      maternal symptoms. The infusion did not result in further fetal compromise. The
      patient delivered a healthy fetus 4 hours after the start of the epinephrine
      infusion. CONCLUSION: This case supports the use of parenteral (intravenous)
      epinephrine for the treatment of anaphylactic reactions during pregnancy.

PMID- 14662224
TI  - Alcohol consumption and the risk of mucinous and nonmucinous epithelial ovarian
      cancer.
AB  - OBJECTIVE: To examine alcohol consumption as a risk factor for epithelial ovarian
      cancer according to tumor histology. METHODS: We examined total alcohol
      consumption and consumption of beer, wine, and spirits as risk factors for
      mucinous and nonmucinous tumors in a population-based, case-control study
      comparing 761 incident cases of epithelial ovarian cancer with 1352 community
      controls frequency-matched to cases by age and three-digit telephone exchange.
      Multivariable, unconditional logistic regression was used to calculate odds
      ratios (ORs) and 95% confidence intervals (CIs) for mucinous and nonmucinous
      tumors associated with alcohol consumption. Adjustments were made for age,
      parity, oral contraceptive use, education, tubal ligation, smoking, and family
      history of ovarian cancer. RESULTS: Overall, no association between total alcohol
      consumption and ovarian cancer was found. However, current heavy alcohol
      consumption (24 g or more per day) was associated with mucinous (OR 1.93; 95% CI
      1.02, 3.65) but not nonmucinous tumors (OR 0.88; 95% CI 0.57, 1.37). The
      association between heavy current consumption and mucinous tumors was strongest
      for spirits (OR 8.83; 95% CI 2.89, 27.01) and apparent for beer (OR 2.53; 95% CI
      0.86, 7.42). For nonmucinous tumors, no such associations were found for either
      spirits (OR 1.53; 95% CI 0.58, 4.00) or beer (OR 0.92; 95% CI 0.39, 2.14).
      CONCLUSION: Current heavy consumption of alcohol might be a risk factor for
      mucinous but not nonmucinous epithelial ovarian cancer. This supports the
      hypothesis of a distinct etiology for mucinous tumors.

PMID- 14662225
TI  - Clinical significance of serum human papillomavirus DNA in cervical carcinoma.
AB  - OBJECTIVE: To study the association between serum human papillomavirus (HPV)
      deoxyribonucleic acid (DNA) and clinicopathologic prognostic factors and the
      clinical usefulness of serum HPV DNA in early-stage cervical cancer. METHODS:
      Deoxyribonucleic acids extracted from cervical tissues and sera of patients with
      stage IB or IIA cervical cancer and 40 controls including patients with cervical
      carcinoma in situ or benign disease were examined for HPV DNA with L1 consensus
      and types 16- and 18-specific E7 primers. Multivariable logistic regression was
      used to determine significant correlates of positive serum HPV DNA, and the
      receiver operating characteristic curve was applied in risk-factor assessment.
      RESULTS: Human papillomavirus DNA was not detected in sera from patients with
      carcinoma in situ or benign disease. Among the 112 patients with cervical cancer,
      we detected 27 positive samples (24.1%) in serum. Positive HPV DNA in serum was
      significantly associated with lymphovascular invasion and deep stromal invasion
      with or without parametrial extension (P <.001 for both conditions), pelvic lymph
      nodal metastasis (P =.001), large tumor size, and elevated levels of serum
      squamous cell carcinoma antigen (P <.001 for both conditions). When serum HPV DNA
      was used to predict high-risk patients who require adjuvant therapy, a
      sensitivity of 45.2%, a specificity of 88.6%, a positive predictive value of
      70.4%, and a negative predictive value of 72.9% were obtained. CONCLUSION: The
      presence of serum HPV DNA in patients with early-stage cervical cancer was
      correlated with poor prognosis factors that warrant adjuvant therapy.

PMID- 14662226
TI  - Risk factors for cesarean delivery at presentation of nulliparous patients in
      labor.
AB  - OBJECTIVE: To identify risk factors that place a term nulliparous patient in
      labor at risk for cesarean delivery. METHODS: This was a case-control, chart
      review study of 325 nulliparous patients presenting in labor at term with
      singleton vertex fetuses with either cesarean (patients) or vaginal (controls)
      delivery. Dichotomous variables were analyzed by chi(2) or Fisher exact tests;
      continuous variables were assessed by the Wilcoxon two-sample test. Multiple
      logistic regression was used to identify independent risk factors for cesarean
      delivery, and a model for predicting risk was built and evaluated. RESULTS: In
      univariate analysis, 22 variables were significantly different between patients
      and controls. Of 11 that were known within 2 hours of admission, five (change in
      cervical dilatation, maternal weight, gestational age, fetal station at 2 hours,
      and preeclampsia) remained independently significant in a multiple logistic
      regression model for cesarean delivery. The multiple regression model could
      divide our study population into quintiles in which the lowest risk group had a
      5% incidence and the highest risk group had an 88% incidence of cesarean
      delivery. CONCLUSION: It may be possible to offer early cesarean delivery to
      patients at highest risk, reducing the potential morbidity of long labor or
      failed operative vaginal delivery followed by a later cesarean delivery.

PMID- 14662227
TI  - Impact of sociodemographic and hospital factors on attempts at vaginal birth
      after cesarean delivery.
AB  - OBJECTIVE: To estimate the clinical and nonclinical factors associated with
      whether a patient attempts a trial of labor after previous cesarean delivery or
      elects to have a repeat cesarean delivery. METHODS: We conducted a retrospective,
      cohort study comparing all women with previous low transverse cesarean delivery
      who attempted a trial of labor with those who elected to have a repeat cesarean
      delivery. Data from 17 hospital sites for the period 1995-1998 were included, for
      a total of 15,172 patients. Bivariate, site-adjusted, and multivariable logistic
      regression analyses were used. RESULTS: Odds of trial of labor by hospital were
      not uniform in the unadjusted or adjusted analyses. The odds of trial of labor
      decreased significantly with increasing age, gravidity, and number of previous
      cesarean deliveries. Medicaid patients had higher odds of trial of labor than did
      privately insured patients (odds ratio [OR] 1.37 [95% confidence interval (CI)
      1.20, 1.55]). Patients with nonrecurrent indication for previous cesarean
      delivery had generally higher odds of trial of labor than did those with a
      recurrent indication. Black women were more likely to attempt trial of labor than
      were white women (OR 2.17 [95% CI 1.83, 2.56] for those with a nonrecurrent
      indication). CONCLUSION: Clinical and nonclinical factors influence rates of
      attempted vaginal birth after cesarean delivery.

PMID- 14662228
TI  - Family history of hypertension, heart disease, and stroke among women who develop
      hypertension in pregnancy.
AB  - OBJECTIVE: To assess familial cardiovascular risk factors in women developing
      hypertension in pregnancy. METHOD: Of 2211 women delivering live births after
      enrollment in a pregnancy cohort study, 85 (3.8%) developed preeclampsia
      (antepartum systolic blood pressure greater than 140 or diastolic blood pressure
      greater than 90 plus proteinuria) and 142 (6.4%) developed transient hypertension
      of pregnancy (antepartum blood pressure elevation without proteinuria). At a mean
      of 10.2 weeks' gestation, women were asked about first-degree family members with
      heart disease or stroke, hypertension, diabetes, renal disease, or any of these,
      which defined familial cardiovascular risk. RESULTS: After adjustment for age and
      body size, having two or more family members, versus no family members, with
      cardiovascular risk imparted a 1.9-fold (95% confidence interval [CI] 1.1, 3.2)
      elevated risk for developing preeclampsia and a 1.7-fold (95% CI 1.1, 2.6) risk
      for developing transient hypertension of pregnancy. Having two or more family
      members with hypertension also imparted a significant, two-fold elevation in risk
      of preeclampsia and transient hypertension of pregnancy, and having two or more
      family members with heart disease or stroke imparted a 3.2-fold (95% CI 1.4, 7.7)
      elevation in the risk for preeclampsia. CONCLUSION: A strong family history of
      aggregate cardiovascular risk increased the likelihood for developing
      preeclampsia and transient hypertension of pregnancy. These findings support the
      theory that a preexisting tendency to cardiovascular risk, and particularly
      hypertension, increases a women's susceptibility to developing hypertension in
      pregnancy.

PMID- 14662229
TI  - Long-term outcome in fetuses with cardiac arrhythmias.
AB  - OBJECTIVE: The objectives of this follow-up study of 292 fetuses with various
      cardiac arrhythmias were to estimate the incidence of structural heart defects
      and fetal compromise, to investigate the effects of antiarrhythmic medication,
      and to evaluate perinatal mortality and morbidity and long-term outcome. METHODS:
      The arrhythmias were classified into atrial extrasystoles (n = 200), atrial
      tachycardias (n = 35), atrioventricular block (n = 36), sinus bradycardia (n =
      14), and ventricular extrasystoles (n = 7), and outcome of the infants was
      analyzed. RESULTS: The incidence of cardiac anomalies was 12% in the study
      population. In utero cardiac failure was noted in 11%. Among fetuses with atrial
      extrasystoles, 1% developed supraventricular tachycardia after birth. During
      antiarrhythmic therapy, sinus rhythm was achieved in 92% of nonhydropic and in
      63% of hydropic fetuses. The latter had higher mortality and risk for neurologic
      morbidity than did nonhydropic fetuses; 38% versus 3.7% and 40% versus 12%,
      respectively. Among fetuses with atrioventricular block only, the survival rate
      was 82%, with a heart defect, prognosis was poor: 50% survived. Sinus bradycardia
      and ventricular extrasystoles were associated with survival rates of 75% and 67%.
      In the follow-up of the whole study population lasting a median 5 years, 93% are
      alive and 3% have a neurologic disorder. CONCLUSION: All fetal arrhythmias except
      atrial extrasystoles were associated with a moderately high risk for fetal
      distress. In cases of compromise, fetal and neonatal prognosis was poor and was
      an indication for perinatal medication. After the newborn period, the prognosis
      has been good. However, the risk for neurologic morbidity must be taken into
      consideration.

PMID- 14662230
TI  - Cerebral metastases of a choriocarcinoma during pregnancy.
AB  - BACKGROUND: Cerebral metastasis of choriocarcinoma during pregnancy is rare.
      Described is the fourth case in the literature. CASE: A pregnant women at 28
      weeks' gestation sought care for headaches followed by loss of consciousness. The
      diagnosis of choriocarcinoma metastases was made on the basis of the combination
      of cerebral and pulmonary lesions, all suspected to be metastatic, and a high
      beta human chorionic gonadotropin level. A premature cesarean delivery was
      performed to improve the mother's prognosis; the responsiveness of
      choriocarcinoma to chemotherapy made it important for treatment to begin as
      rapidly as possible. The outcome has been on balance favorable, even though her
      sequelae include paraplegia. The child has no apparent sequelae. CONCLUSION: The
      diagnosis of choriocarcinoma must be considered when acute neurological signs
      appear in a pregnant patient.

PMID- 14662231
TI  - Total laparoscopic hysterectomy: body mass index and outcomes.
AB  - OBJECTIVE: This retrospective review of patients undergoing total laparoscopic
      hysterectomy examines whether differences in outcomes exist on the basis of body
      mass index (BMI). METHODS: All cases of total laparoscopic hysterectomy performed
      from September 1996 to July 2002 for benign diagnoses, and microinvasive
      cervical, early endometrial, and occult ovarian carcinoma were reviewed. There
      were 330 patients analyzed by BMI category (range, 18.5-54.1): ideal (n = 150)
      less than 24.9 kg/m(2), overweight (n = 95) 25 to 29.9 kg/m(2), and obese (n =
      78) 30 kg/m(2) or more. Seven patients were converted to laparotomy (four ideal
      BMI, two overweight, one obese) leaving 323 (98%) for analysis. Mean age (50
      years), height (65 in.), and parity (1.2) were similar, with 39% nulligravidas in
      each group. RESULTS: Mean operating time (156 minutes), blood loss (160 mL), and
      length of hospital stay (1.9 days) did not vary by BMI group. Total complication
      rates (8.9%), and major (5.5%) and minor (3.4%) complication rates were similar
      in each BMI group. Urologic injury was observed in 3.1%, with two-thirds
      occurring in the first one-third of the patient series. CONCLUSION: Total
      laparoscopic hysterectomy is feasible and safe, resulting in short hospital stay,
      minimal blood loss, and minimal operating time for patients in all BMI groups.
      The laparoscopic approach may extend the benefits of minimally invasive
      hysterectomy to the very obese, for whom abdominal surgery poses serious risk.

PMID- 14662232
TI  - Lown-Ganong-Levine syndrome in pregnancy.
AB  - BACKGROUND: Lown-Ganong-Levine syndrome is characterized by paroxysmal
      supraventricular tachycardia, a short PR interval, and normal QRS. CASE: A
      gravida 3, para 2 was diagnosed with Lown-Ganong-Levine syndrome at 16 weeks'
      gestation after an episode of chest pain and shortness of breath. She was
      hospitalized and treated with digoxin, and her symptoms subsided. The remainder
      of her pregnancy was uneventful. CONCLUSION: Lown-Ganong-Levine Syndrome is a
      rare complication most commonly seen in young to middle-aged women. This syndrome
      can be treated and controlled medically with a good outcome.

PMID- 14662233
TI  - Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a
      systematic review.
AB  - OBJECTIVE: Genital herpes simplex virus (HSV) infection is one of the most common
      viral sexually transmitted diseases in the United States. Perinatal transmission
      of the virus to the fetus or neonate is a major concern in affected pregnancies.
      Our objective was to systematically review published data to estimate the effect
      of prophylactic acyclovir provided to pregnant women near term on the rate of
      recurrent genital herpes at delivery; the number of cesarean deliveries performed
      for clinical HSV recurrences or prodromal symptoms; and the prevalence of HSV
      virologic detection at delivery. DATA SOURCES: Our search included MEDLINE (1966
      March 2003), LILACS, EMBASE, conference proceedings, abstracts from scientific
      forums and bibliographies of published articles with the following medical
      headings: acyclovir, pregnancy, Herpes viridae, and Herpesviridae. METHODS OF
      STUDY SELECTION: Prospectively designed criteria included randomized, clinical
      trials detailing the use of acyclovir in pregnancy for women with HSV published
      in either abstract or article form. Five trials with a total enrollment of 799
      patients were included in the analysis. TABULATION, INTEGRATION, AND RESULTS: The
      studies were reviewed independently by three of the authors. With RevMan
      software, a fixed-effects model was used to calculate a summary odds ratio (OR)
      comparing the effect of treatment with placebo. Acyclovir prophylaxis beginning
      at 36 weeks' gestation was effective in reducing clinical HSV recurrences at the
      time of delivery (OR 0.25; 95% confidence interval [95% CI] 0.15, 0.40), cesarean
      deliveries for clinical recurrence genital herpes (OR 0.30; 95% CI 0.13, 0.67),
      total HSV detection at delivery (OR 0.11; 95% CI 0.04, 0.31), and asymptomatic
      HSV shedding at delivery (OR 0.09; 95% CI 0.02, 0.39). CONCLUSION: The results of
      this meta-analysis indicate that prophylactic acyclovir beginning at 36 weeks'
      gestation reduces the risk of clinical HSV recurrence at delivery, cesarean
      delivery for recurrent genital herpes, and the risk of HSV viral shedding at
      delivery.

PMID- 14662234
TI  - Imaging in appendicitis: a review with special emphasis on the treatment of
      women.
AB  - OBJECTIVE: Acute abdominal pain in women often presents the clinician with a
      diagnostic dilemma, especially if it is lower abdominal pain. Appendicitis is
      frequently entertained as a diagnosis, but until recently, the gold standard
      diagnostic procedure was operation, carrying a high false-negative rate. In
      recent years, computed tomographic (CT) scan has been advocated as a diagnostic
      aid. The purpose of this systematic review was to evaluate the accuracy of CT
      scan in diagnosing appendicitis. DATA SOURCES: Investigators searched PubMed
      between January and July 2003 using the terms "CT scan" and "appendicitis" with
      the limits "All adults 19+ years" and "English [language]." In addition,
      reference lists of all obtained articles were reviewed for other potential
      citations. METHODS OF STUDY SELECTION: All prospective studies of adults
      published in English were considered. TABULATION, INTEGRATION, AND RESULTS:
      Initial searches and reviews yielded 248 citations. Twenty-three of the citations
      reported prospective studies; only two of these were randomized studies.
      Prospective studies report sensitivities ranging from 77% to 100%, specificities
      ranging from 83% to 100%, and accuracies ranging from 88% to 98% for the
      diagnosis of acute appendicitis. Information gained from CT scans in patients
      with suspected appendicitis results in alternative diagnosis in 6% to 36%. These
      values are similar for both men and women. CONCLUSION: The data support routine
      use of CT scan in both men and women for the diagnosis of appendicitis.

PMID- 14662236
TI  - Breastfeeding: it's an important gift.

PMID- 14662237
TI  - Breastfeeding: it's an important gift.

PMID- 14662238
TI  - The effect of childbirth on pelvic organ mobility.

PMID- 14662240
TI  - Evidence for asymmetric distribution of sciatic nerve endometriosis.

PMID- 14662242
TI  - Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time
      for reevaluation.

PMID- 14662243
TI  - ACOG Practice Bulletin Number 49, December 2003: Dystocia and augmentation of
      labor.

PMID- 14662244
TI  - Clinical utility of computed tomography and magnetic resonance techniques for
      noninvasive coronary angiography.
AB  - OBJECTIVE: The purpose of this study was to provide a comprehensive review of the
      literature relating to electron beam angiography (EBA), magnetic resonance
      angiography, and spiral computed tomography, currently the three most promising
      noninvasive methods to visualize obstructions in the coronary tree. BACKGROUND:
      Given the high costs and invasiveness of coronary angiography, there is increased
      interest in noninvasive coronary angiography, which has made great strides to
      become a clinically useful tool to augment conventional coronary angiography
      (CCA). METHODS: MEDLINE searches were performed to include all articles related
      to noninvasive angiography utilizing either magnetic resonance imaging (MRI),
      multi-row detector spiral computed tomography (MDCT), and electron beam
      tomography (EBT). Weighted analysis was performed to define the published
      sensitivity and specificity for each technique. RESULTS: Electron beam
      angiography (EBA) provides an overall sensitivity of 87% and specificity of 91%
      for the detection of obstructive coronary artery disease (CAD). Four-level MDCT
      data demonstrated an overall sensitivity of 59% and specificity of 89%, with
      higher accuracy in two recent studies of 16-level detector devices. Magnetic
      resonance angiography demonstrated sensitivity for detection of obstructive CAD
      of 77% and specificity of 71%. CONCLUSIONS: Noninvasive coronary angiography is a
      rapidly developing technique and currently not an alternative to CCA in all
      cases. All three methods are currently used clinically in certain centers with
      appropriate expertise. Selective use should prove both cost-effective and provide
      a safer, less-invasive method for patients to determine the need for medical
      versus revascularization therapy.

PMID- 14662245
TI  - A randomized trial comparing primary infarct artery stenting with or without
      abciximab in acute myocardial infarction.
AB  - OBJECTIVES: We sought to evaluate the efficacy of abciximab as adjunctive therapy
      to routine infarct-related artery (IRA) stenting. BACKGROUND: The impact of
      abciximab on the efficacy of myocardial reperfusion and the outcome of patients
      with acute myocardial infarction (AMI) undergoing IRA stenting have not yet been
      defined. METHODS: In a randomized trial, we assigned 400 patients with AMI to
      undergo IRA stenting alone or stenting plus abciximab. The primary end point was
      a composite of death, reinfarction, target vessel revascularization (TVR), and
      stroke at one month. RESULTS: The incidence of the primary end point was lower in
      the abciximab group than in the stent only group (4.5% and 10.5%, respectively; p
      = 0.023), and randomization to abciximab was independently related to the risk of
      the primary end point (odds ratio 0.41, 95% confidence interval 0.17 to 0.97; p =
      0.041). Early ST-segment resolution was more frequent in the abciximab group (85%
      vs. 68%, p < 0.001). Infarct size, as assessed by one-month technetium-99m
      sestamibi scintigraphy, revealed smaller infarcts in the abciximab group. At six
      months, the cumulative difference in mortality between the groups increased (4.5%
      vs. 8%), and the incidence of the composite of six-month death and reinfarction
      was lower in the abciximab group than in the stent only group (5.5% and 13.5%,
      respectively; p = 0.006). Six-month repeat TVR and restenosis rates were similar
      in the two groups. CONCLUSIONS: Abciximab plus IRA stenting should be considered
      the routine reperfusion strategy in patients with AMI undergoing primary
      percutaneous mechanical revascularization, especially in high-risk patients.

PMID- 14662246
TI  - A preferred reperfusion strategy for acute myocardial infarction.

PMID- 14662247
TI  - Simplified scoring system for predicting mortality after percutaneous coronary
      intervention.
AB  - OBJECTIVES: We sought to develop a simplified scoring system based on pre
      intervention clinical characteristics to predict in-hospital mortality after
      percutaneous coronary intervention (PCI). BACKGROUND: Percutaneous coronary
      intervention is associated with variety of complications, including the risk of
      death. Factors leading to poor outcomes need to be identified. Currently
      available indexes are cumbersome and therefore seldom used. METHODS: Crude
      mortality and univariate odds ratios (ORs) for mortality associated with multiple
      clinical characteristics were calculated for 9,954 patients undergoing PCI at the
      William Beaumont Hospital during 1996 to 1998. Based on the OR, each factor was
      assigned a weighted score. Using these scores, a classification was constructed
      to determine the probability of death after PCI, with classes I through IV
      representing an increasing probability of procedural mortality. This
      classification was validated in a separate group of patients. RESULTS: The
      factors with the highest univariate odds of dying and their scores were:
      myocardial infarction <14 days = 7; elevated creatinine = 4; multivessel disease
      = 4; and age >65 years = 3. Classes were created based on the presence of these
      factors in a given patient. The odds of dying and mortality increased
      significantly with each class. These results were reproduced in the validation
      subset. CONCLUSIONS: Preprocedural clinical risk factors have a differential
      influence on the probability of death after PCI. Risk classification based on
      these factors can be used to accurately predict the procedural outcome. This
      simple classification can be used by interventionalists to assist in management
      decisions, to provide an estimate of procedural risk to the patients and
      relatives, and for quality assurance.

PMID- 14662248
TI  - Risk assessment for percutaneous coronary intervention: our version of the
      weather report?

PMID- 14662249
TI  - Increased CK-MB release is a "trade-off" for optimal stent implantation: an
      intravascular ultrasound study.
AB  - OBJECTIVES: We sought to determine the impact of aggressive stent expansion on
      creatine kinase-MB isoenzyme (CK-MB) release and clinical restenosis. BACKGROUND:
      Elevation of CK-MB after percutaneous coronary interventions has been associated
      with late mortality. METHODS: We identified 989 consecutive patients who
      underwent intravascular ultrasound-guided stenting of 1,015 coronary lesions.
      Patients were divided into three groups according to stent expansion, defined as
      the ratio of final lumen over the reference lumen cross-sectional areas: Group 1
      (ratio <70%, n = 117 patients with 126 lesions); Group 2 (ratio 70% to 100%, n =
      551 patients with 562 lesions); Group 3 (ratio >100%, n = 321 patients with 327
      lesions). RESULTS: The peak CK-MB values increased significantly with increasing
      stent expansion: CK-MB = 3 to 5x normal occurred 16%, 18%, and 25% in Groups 1,
      2, and 3, respectively, p = 0.02; CK-MB >5 times normal occurred 9%, 13%, and 16%
      respectively, p = 0.02. Conversely, at one year follow-up there was a stepwise
      decrease in target lesion revascularization (11% vs. 19% and 17%, respectively, p
      = 0.04) and major adverse cardiac events with increasing stent expansion. In
      addition, there was a trend toward lower mortality in Group 3 (9% vs. 4.4% vs.
      4.0%, p = 0.07). CONCLUSIONS: Intravascular ultrasound-guided stent overexpansion
      (final lumen greater than reference lumen cross-sectional area) is accompanied by
      a higher periprocedural CK-MB release but a lower target lesion revascularization
      and a trend toward lower mortality at one year. Increased periprocedural CK-MB
      release appears as a trade-off for optimal stent implantation and lower clinical
      restenosis.

PMID- 14662250
TI  - A twist in our understanding of enzyme elevation after coronary intervention.

PMID- 14662251
TI  - N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial
      necrosis, and the effect of an invasive strategy in unstable coronary artery
      disease.
AB  - OBJECTIVES: We sought to examine whether measurements of N-terminal pro-brain
      natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and
      interleukin-6 (IL-6), improve the ability to identify high-risk patients who
      benefit from an early invasive strategy. BACKGROUND: Biochemical indicators of
      cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial
      damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD)
      (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]).
      In these patients, an early invasive treatment strategy improves the outcome.
      METHODS: Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with
      UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast
      revascularization during InStability in Coronary artery disease (FRISC-II) trial.
      Patients were followed up for two years to determine death and MI. RESULTS:
      Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval
      [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non
      invasive and invasive groups, respectively. An increased NT-proBNP level was
      independently associated with mortality. In patients with increased levels of
      both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3%
      (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6
      levels, the mortality was not reduced. Only elevated cTnT was independently
      associated with future MI and a reduction of MI by means of an invasive strategy.
      CONCLUSIONS: N-terminal proBNP is independently associated with mortality. The
      combination of NT-proBNP and IL-6 seems to be a useful tool in the identification
      of patients with a definite survival benefit from an early invasive strategy.
      Only cTnT is independently associated with future MI and a reduction of MI by an
      invasive strategy.

PMID- 14662252
TI  - Use of brain natriuretic peptide levels for risk assessment in non-ST-elevation
      acute coronary syndromes.

PMID- 14662253
TI  - Determinants of exercise-induced changes in mitral regurgitation in patients with
      coronary artery disease and left ventricular dysfunction.
AB  - OBJECTIVES: We sought to examine the determinants of exercise-induced changes in
      ischemic mitral regurgitation (MR) in patients with left ventricular (LV)
      dysfunction. BACKGROUND: In the post-myocardial infarction (MI) phase, ischemic
      MR contributes to worsening of symptoms and of LV dysfunction. METHODS: In this
      study, 70 patients in the chronic, post-MI phase, with LV ejection fraction <45%
      and at least mild MR, underwent semi-supine exercise Doppler echocardiography.
      The effective regurgitant orifice (ERO) of MR was quantified at rest and during
      exercise. Exercise-induced changes in ERO were compared with changes in mitral
      deformation and in local and global LV remodeling. RESULTS: The wide range of
      exercise-induced ERO changes that were observed was unrelated to the degree of MR
      at rest (r = 0.20). Effective regurgitant orifice changes correlated best with
      changes in mitral deformation (i.e., differences in systolic mitral tenting area,
      systolic annular area, and coaptation height) (p < 0.0001). Posterior
      displacement of the papillary muscles was associated with larger changes in the
      ERO in both infarct groups. In patients with inferior MI, a decrease in the ERO
      was related to improvement in wall motion (r = 0.68). The independent predictors
      of ERO changes during exercise were changes in systolic annular area for all
      infarct categories, in tenting area and wall motion score in the global
      population and those with inferior infarction, and in apical displacement of
      mitral leaflets for patients with anterior MI. CONCLUSIONS: The degree of MR at
      rest is unrelated to exercise-induced changes in EROs, which are related to those
      in local LV remodeling and in mitral deformation but not those in global LV
      function.

PMID- 14662254
TI  - Ischemic mitral regurgitation, the dynamic lesion: clues to the cure.

PMID- 14662255
TI  - The relationship between cholesterol and survival in patients with chronic heart
      failure.
AB  - OBJECTIVES: We sought to describe the relationship between cholesterol and
      survival in patients with chronic heart failure (CHF). BACKGROUND: Increasing
      lipoprotein levels are a cardiovascular risk factor. In patients with CHF, the
      prognostic value of endogenous lipoproteins is not fully clarified. METHODS: A
      group of 114 patients with CHF recruited to a metabolic study was followed for a
      minimum of 12 months (derivation study). The results were applied to a second
      group of 303 unselected patients with CHF (validation study). The relationship
      between endogenous lipoproteins and survival was explored. RESULTS: In the
      derivation study, survival at 12 months was 78% (95% confidence interval [CI] 70%
      to 86%) and 56% (95% CI 51% to 62%) at 36 months. Increasing total serum
      cholesterol was a predictor of survival (hazard ratio 0.64, 95% CI 0.48 to 0.86),
      independent of the etiology of CHF, age, left ventricular ejection fraction, and
      exercise capacity. Receiver-operating characteristic curves demonstrated a best
      cut-off value of </=5.2 mmol/l (200.8 mg/dl) as being the best predictor of
      mortality at 12 months (sensitivity 80.0%, specificity 62.9%). In the validation
      population, one-year survival was 88% (95% CI 84 to 91%) and three-year survival
      was 68% (95% CI 63 to 73%). The chance of survival increased 25% for each mmol/l
      increment in total cholesterol. Survival rates above and below the cut-off value
      for cholesterol in patients with ischemic heart disease (n = 181) were 92% (95%
      CI 89 to 94) versus 75% (95% CI 64 to 85%) at one year and 72% (95% CI 67 to 76%)
      versus 50% (95% CI 43 to 56%) at three years. CONCLUSIONS: In patients with CHF,
      lower serum total cholesterol is independently associated with a worse prognosis.

PMID- 14662256
TI  - Cholesterol and mortality in heart failure: the bad gone good?

PMID- 14662257
TI  - Carvedilol alone or in combination with digoxin for the management of atrial
      fibrillation in patients with heart failure?
AB  - OBJECTIVES: This study examined the relative merits of digoxin, carvedilol, and
      their combination for the management of patients with atrial fibrillation (AF)
      and heart failure (HF). BACKGROUND: In patients with AF and HF, both digoxin and
      beta-blockers reduce the ventricular rate, and both may improve symptoms, but
      only beta-blockers have been shown to improve prognosis. If combined therapy is
      not superior to beta-blockers alone, treatment of patients with HF and AF could
      be simplified by stopping digoxin. METHODS: We enrolled 47 patients (29 males;
      mean age 68 years) with persistent AF and HF (mean left ventricular ejection
      fraction [LVEF] 24%) in a randomized, double-blinded, placebo-controlled study.
      In the first phase of the study, digoxin was compared with the combination of
      digoxin and carvedilol (four months). In the second phase, digoxin was withdrawn
      in a double-blinded manner in the carvedilol-treated arm, thus allowing a
      comparison between digoxin and carvedilol (six months). Investigations were
      undertaken at baseline and at the end of each phase. RESULTS: Compared with
      digoxin alone, combination therapy lowered the ventricular rate on 24-h
      ambulatory electrocardiographic monitoring (p < 0.0001) and during submaximal
      exercise (p < 0.05), whereas LVEF (p < 0.05) and symptom score (p < 0.05)
      improved. In phase 2, there was no significant difference between digoxin alone
      and carvedilol alone in any variable. The mean ventricular rate rose and LVEF
      fell when patients switched from combination therapy to carvedilol alone. Six
      minute walk distance was not significantly influenced by any therapy.
      CONCLUSIONS: The combination of carvedilol and digoxin appears generally superior
      to either carvedilol or digoxin alone in the management of AF in patients with
      HF.

PMID- 14662258
TI  - Magnetic guidance system for cardiac electrophysiology: a prospective trial of
      safety and efficacy in humans.
AB  - OBJECTIVES: We evaluated in humans the safety and efficacy of a novel magnetic
      guidance system (MGS) for electrophysiological mapping, pacing, and ablation.
      BACKGROUND: Catheter ablation of atrial fibrillation and other complex
      arrhythmias requires precise catheter manipulation and stabilization. We have
      shown in animals that the MGS can precisely manipulate a mapping catheter within
      the heart with an external magnetic field rather than manual catheter control.
      METHODS: Thirty-one adults referred for diagnostic electrophysiology studies were
      enrolled in a prospective trial of the MGS. The magnetic catheter was navigated
      to preselected sites in the right atrium (RA) and right ventricle (RV) in the
      first 20 patients. Electrograms were recorded at each target site, and pacing
      thresholds were measured. In a subset of five patients, RA and RV electrograms
      and stimulation thresholds were recorded with both a standard ablation catheter
      and the magnetic catheter. Eleven additional patients were recruited for
      supraventricular tachycardia (SVT) mapping, and seven of these underwent
      ablation. RESULTS: Navigation was successful in 200 of 202 predetermined right
      sided navigation targets and 13 of 13 targets in the left atria. Pacing
      thresholds and electrogram amplitudes in the RA and RV were not significantly
      different between the standard and magnetic catheters. The SVT mapping with the
      magnetic catheter was successful in 13 patients, including 4 with left-sided
      accessory pathways. The MGS was used for successful ablation of SVT in seven of
      seven patients. There were no procedural complications. CONCLUSIONS: These
      results demonstrate that the MGS can be used for intracardiac mapping, pacing,
      and ablation safely and effectively.

PMID- 14662259
TI  - Does sports activity enhance the risk of sudden death in adolescents and young
      adults?
AB  - OBJECTIVES: We sought to assess the risk of sudden death (SD) in both male and
      female athletes age 12 to 35 years. BACKGROUND: Little is known about the risk of
      SD in adolescents and young adults engaged in sports. METHODS: We did a 21-year
      prospective cohort study of all young people of the Veneto Region of Italy. From
      1979 to 1999, the total population of adolescents and young adults averaged
      1,386,600 (692,100 males and 694,500 females), of which 112,790 (90,690 males and
      22,100 females) were competitive athletes. An analysis by gender of risk of SD
      and underlying pathologic substrates was performed in the athletic and non
      athletic populations. RESULTS: There were 300 cases of SD, producing an overall
      cohort incidence rate of 1 in 100,000 persons per year. Fifty-five SDs occurred
      among athletes (2.3 in 100,000 per year) and 245 among non-athletes (0.9 in
      100,000 per year), with an estimated relative risk (RR) of 2.5 (95% confidence
      interval [CI] 1.8 to 3.4; p < 0.0001). The RR of SD among athletes versus non
      athletes was 1.95 (CI 1.3 to 2.6; p = 0.0001) for males and 2.00 (CI 0.6 to 4.9;
      p = 0.15) for females. The higher risk of SD in athletes was strongly related to
      underlying cardiovascular diseases such as congenital coronary artery anomaly (RR
      79, CI 10 to 3,564; p < 0.0001), arrhythmogenic right ventricular cardiomyopathy
      (RR 5.4, CI 2.5 to 11.2; p < 0.0001), and premature coronary artery disease (RR
      2.6, CI 1.2 to 5.1; p = 0.008). CONCLUSIONS: Sports activity in adolescents and
      young adults was associated with an increased risk of SD, both in males and
      females. Sports, per se, was not a cause of the enhanced mortality, but it
      triggered SD in those athletes who were affected by cardiovascular conditions
      predisposing to life-threatening ventricular arrhythmias during physical
      exercise.

PMID- 14662260
TI  - Identifying athletes at risk for sudden death.

PMID- 14662261
TI  - Dehydroepiandrosterone, an adrenal androgen, increases human foam cell formation:
      a potentially pro-atherogenic effect.
AB  - OBJECTIVES: We studied the effects of dehydroepiandrosterone (DHEA), an abundant
      adrenal androgen on two key early events of atherogenenis: 1) human monocyte
      adhesion to vascular endothelium, and 2) human foam cell formation. BACKGROUND:
      In the U.S., where DHEA is available without prescription, there has recently
      been a rapid increase in unsupervised self-administration of DHEA. The vascular
      biologic effects of DHEA are largely unknown, however. METHODS: Regarding
      adhesion, human umbilical vein endothelial cells (HUVECs), exposed to either DHEA
      (42 or 420 nmol/l) or control, were incubated with human monocytes, and adhesion
      was measured by hemocytometry. Surface expression of endothelial cell adhesion
      molecules was measured by ELISA. Regarding foam cell formation, studies of lipid
      loading were performed on macrophages treated with DHEA or control and/or the
      androgen receptor antagonist hydroxyflutamide (HF) (4 micromol/l). Intracellular
      cholesterol and cholesteryl esters (CE) were quantified by high-performance
      liquid chromatography. Expression of foam cell formation-related genes was
      measured by reverse-transcription polymerase chain reaction. RESULTS: DHEA
      produced a dose-dependent receptor-mediated increase in the male macrophage CE
      content (up to 120 +/- 4% of control values, p = 0.015). DHEA upregulated
      messenger ribonucleic acid expression of the lipoprotein-processing enzymes acyl
      coenzyme A:cholesterol acyltransferase I and lysosomal acid lipase by 3.4- and
      5.3-fold, respectively (p < 0.05 vs. control), but had no effect on scavenger
      receptor expression (p > 0.2). There was no significant effect of DHEA on
      monocyte-endothelial adhesion (<10% change in values, p = 0.56) or endothelial
      cell expression of cell adhesion molecules (p > 0.1). CONCLUSIONS: DHEA increases
      human macrophage foam cell formation, a potentially pro-atherogenic effect. This
      effect appears to be mediated via the androgen receptor and involves the
      upregulation of lipoprotein-processing enzymes.

PMID- 14662262
TI  - Endothelin-1 regulates arterial pulse wave velocity in vivo.
AB  - OBJECTIVES: The aim of this study was to investigate whether endothelin-1, acting
      locally, regulates arterial distensibility, assessed by measuring pulse-wave
      velocity in vivo. BACKGROUND: Arterial stiffness is a key determinant of
      cardiovascular risk. Several lines of evidence support a role for the endothelium
      in regulating arterial stiffness by release of vasoactive mediators. However, the
      role of endothelin-1 (ET-1) in the regulation of arterial stiffness has not been
      investigated. METHODS: All studies were conducted in anesthetized sheep. Pulse
      wave velocity (PWV) was calculated using the foot-to-foot methodology from two
      pressure waveforms simultaneously recorded with a high-fidelity, dual pressure
      sensing catheter placed in the common iliac artery. RESULTS: Intra-arterial
      infusion of ET-1 significantly increased iliac PWV by 12 +/- 5% (mean +/- STD; p
      < 0.001), whereas infusion of the endothelin-A (ET(A)) receptor antagonist BQ-123
      significantly reduced PWV by 12 +/- 4% (p < 0.001). After BQ-123 infusion,
      exogenously infused ET-1 did not significantly change PWV compared with infusion
      of saline (change of -0.08 +/- 0.11% vs. -0.01 +/- 0.07%; p = 0.53). Importantly,
      infusion of BQ-123 or ET-1 distal to the common iliac artery did not affect PWV.
      CONCLUSIONS: These results demonstrate, for the first time, that endogenous ET-1
      production directly regulates large artery PWV in vivo. In addition, exogenous ET
      1 increases PWV, and this can be blunted by ET(A) receptor blockade. These
      observations explain, in part, why conditions that exhibit up-regulation of ET-1
      are also associated with arterial stiffening. Therefore, drugs that block ET(A)
      receptors may be effective in reducing large artery stiffness in humans, and thus
      cardiovascular risk.

PMID- 14662263
TI  - Pulmonary thrombosis in adults with Eisenmenger syndrome.
AB  - OBJECTIVES: We sought to determine the prevalence of pulmonary artery thrombosis
      in patients with Eisenmenger syndrome and to identify individuals at highest
      risk. BACKGROUND: Eisenmenger syndrome is associated with pulmonary arterial
      thrombus formation. Both the prevalence and the determinants of pulmonary
      arterial thrombosis are unknown. METHODS: This is a review of patients with
      Eisenmenger syndrome seen at the Toronto Congenital Cardiac Centre for Adults,
      Canada. Patients underwent a contrast-enhanced computed tomographic (CT) scan of
      the thorax. RESULTS: Forty-nine consecutive patients with Eisenmenger syndrome
      were seen in our hospital. Fifteen patients did not undergo CT angiograms;
      therefore, 34 patients (mean age 42 +/- 10 years) were included in the study.
      Responsible shunts included ventricular septal defect (65%), atrial septal defect
      (15%), patent ductus arteriosus (9%), and other (11%). The prevalence of proximal
      pulmonary artery thrombus was 21% (7/34) of patients. Evidence of more distal
      vessel thrombosis was observed in 43% (3/7) of the patients who had visible
      thrombus in the proximal pulmonary arteries. Patients with thrombus were more
      likely to be female (86% vs. 37%, p = 0.04) and to have lower oxygen saturations
      (72% +/- 9% vs. 85% +/- 6%, p = 0.01). Differences in functional status did not
      identify patients at highest risk for thrombosis. CONCLUSIONS: Patients with
      Eisenmenger syndrome have a substantial risk of pulmonary artery thrombus
      formation. Women and patients with lower oxygen saturations are at the highest
      risk of developing thrombosis. In the context of an increased bleeding tendency
      in these patients, the role of anticoagulation treatment needs to be determined.

PMID- 14662264
TI  - Characteristics and management of cleft mitral valve.
AB  - OBJECTIVES: We sought to highlight the clinical, morphologic, and pathogenetic
      features in patients with a cleft mitral valve (MV). BACKGROUND: Few studies have
      addressed the morphologic features of cleft MV and the outcome of these patients.
      The pathogenetic features, including the developmental relation to an
      atrioventricular (AV) septal defect, remain unclear. METHODS: We reviewed the
      patients with cleft MV that were diagnosed by echocardiography since 1980.
      Patients with an AV canal, ventriculo-arterial discordance, and hypoplastic
      ventricles were excluded. RESULTS: Twenty-two patients were identified at a
      median age of 0.5 years (range 0 to 10.6). In three patients, no chordal
      attachments of the cleft to the ventricular septum were seen. Ten patients had
      significant mitral regurgitation (MR), and three had subaortic obstruction by the
      cleft. Associated cardiac lesions and extracardiac features were present in 13
      and 10 patients, respectively. During the median follow-up period of 1.5 years
      (range 0 to 11.8), two patients died of extracardiac causes, and one neonate died
      of severe subaortic obstruction. Surgical repair was performed in 10 patients at
      a median age of 5.2 years (range 1.3 to 10.6). Multivariate analysis showed no
      predictors for MV surgery. One patient was re-operated for mitral stenosis
      associated with aortic valve stenosis. Follow-up echocardiography demonstrated
      moderate MR in two unoperated patients and moderate MV stenosis in two operated
      patients. CONCLUSIONS: A cleft of the MV comprises a wide spectrum. Important
      morphologic differences exist with an AV septal defect, although the two lesions
      may be pathogenetically related. Surgical repair always seems possible. Long-term
      echocardiographic follow-up is warranted.

PMID- 14662265
TI  - Phospholipid abnormalities in children with Barth syndrome.
AB  - OBJECTIVES: We sought to identify characteristic lipid abnormalities in patients
      with Barth syndrome (BTHS) and to correlate the lipid profile to phenotype and
      genotype. BACKGROUND: Barth syndrome typically includes cardiomyopathy, skeletal
      myopathy, neutropenia, growth retardation, and 3-methylglutaconic aciduria, and
      it is commonly associated with mutations in the tafazzin (TAZ) gene, whose
      products are homologous to phospholipid acyltransferases. However, clinical
      features of BTHS have also been found in patients with normal TAZ gene. METHODS:
      We analyzed molecular species of phospholipids in left and right ventricle,
      skeletal muscle, platelets, lymphoblasts, and fibroblasts from 19 children with
      BTHS (positive TAZ mutation), 6 children with BTHS-like syndromes (wild-type
      TAZ), 4 children with isolated cardiomyopathy (wild-type TAZ), and various
      controls. RESULTS: Cardiolipin, the specific lipid found only in mitochondria,
      was decreased in all tissues from BTHS patients, whereas concentrations of other
      phospholipids were normal. The molecular composition of cardiolipin was altered
      in all tissues from BTHS patients. The molecular compositions of
      phosphatidylcholine and phosphatidylethanolamine were altered in the heart.
      Cardiolipin abnormalities were only found in children with true BTHS, not in
      children with BTHS-like disease or with isolated cardiomyopathy. The degree of
      cardiolipin deficiency was tissue-specific but did not correlate with severity or
      specific phenotypic expression of BTHS. CONCLUSIONS: Abnormal cardiolipin is a
      specific diagnostic marker of cardiomyopathies caused by TAZ mutations. These
      mutations lead to alterations in the fatty acid composition of several
      phospholipids, supporting the idea that TAZ encodes a human acyltransferase.

PMID- 14662266
TI  - Attenuation of virus-induced myocardial injury by inhibition of the angiotensin
      II type 1 receptor signal and decreased nuclear factor-kappa B activation in
      knockout mice.
AB  - OBJECTIVES: This study examined the role of angiotensin II (Ang-II) in a murine
      model of viral myocarditis. BACKGROUND: Ang-II plays an important role in the
      pathophysiology of various cardiovascular disorders. However, the role of Ang-II
      in inflammatory heart diseases is not known. METHODS: Four-week-old wild-type
      (WT) and Ang-II type 1 receptor (AT(1)R) knockout (KO) mice were inoculated with
      the encephalomyocarditis virus (EMCV). Survival, histopathology, expression of
      proinflammatory cytokines, and activity of nuclear factor-kappa B (NF-kB) in the
      heart were examined. RESULTS: The 14-day survival was significantly increased in
      KO compared with WT mice. Histopathologic scores for myocardial necrosis (0.86 +/
      0.69 vs. 2.44 +/- 0.88, p < 0.01) and cellular infiltration (0.86 +/- 0.38 vs.
      2.33 +/- 0.50, p < 0.01) were lower in KO than in WT mice. The expression of
      tumor necrosis factor-alpha (TNF-alpha) was increased 43.2-fold, that of
      interleukin-1-beta (IL-1-beta) 45.8-fold, and the activity of NF-kB 2.24-fold by
      EMCV inoculation in WT mice (each p < 0.01), but not in KO mice (5.9-fold, 6.3
      fold, and 1.12-fold, respectively, each p = NS). The AT(1)R blocker also
      significantly attenuated the expression of proinflammatory cytokines and the
      activation of NF-kB in virus-inoculated WT mice. Intravenous Ang-II injection
      enhanced the activation of NF-kB (2.28-fold, p < 0.01) and increased the
      expression of TNF-alpha (2.31-fold, p < 0.01) and IL-1-beta (2.45-fold, p < 0.01)
      in heart tissue of WT but not KO mice. CONCLUSIONS: These results indicate that
      the AT(1)R signal is obligatory for the development of virus-induced myocardial
      injury through the proinflammatory action of Ang-II via the NF-kB/cytokine
      pathway.

PMID- 14662267
TI  - Prospective, randomized evaluation of thrombectomy prior to percutaneous
      intervention in diseased saphenous vein grafts and thrombus-containing coronary
      arteries.
AB  - OBJECTIVES: We sought to determine whether routine thrombectomy prior to stent
      implantation in diseased saphenous vein grafts (SVGs) and thrombus-containing
      native coronary arteries would reduce peri-procedural myonecrosis and
      subsequently enhance event-free survival. BACKGROUND: Percutaneous coronary
      intervention in diseased SVGs and thrombotic native coronary arteries is
      complicated by a high rate of peri-procedural myocardial infarction (MI).
      Thrombectomy prior to intervention may enhance the safety of intervention and
      improve early and late outcomes in these high-risk patients. METHODS: At 60
      centers in the U.S. and Canada, 797 patients with 839 diseased SVGs or thrombus
      containing native coronary arteries were prospectively randomized to stent
      implantation with versus without prior thrombectomy with the X-SIZER device (ev3,
      Plymouth, Minnesota). RESULTS: Peri-procedural MI occurred in 15.8% of patients
      assigned to the X-SIZER device compared with 16.6% of control patients (p =
      0.77), although the rate of large MI (pre-specified as the development of new
      pathologic Q waves or creatine phosphokinase-MB isoenzyme elevation >8 x upper
      limits of normal) was reduced with X-SIZER device use from 9.6% to 5.5%
      (multivariate risk ratio 0.35 [95% confidence interval 0.18 to 0.66], p = 0.002).
      Major adverse cardiac events (cardiac death, MI, or repeat target vessel
      revascularization) occurred in 16.8% of X-SIZER patients versus 17.1% of control
      patients at 30 days (p = 0.92), and in 31.3% of X-SIZER patients versus 28.2% of
      control patients at 1 year (p = 0.35). CONCLUSIONS: Thrombectomy with the X-SIZER
      device prior to stent implantation in high-risk diseased SVGs and thrombus
      containing native coronary arteries may reduce the extent, but not the
      occurrence, of myonecrosis. Early and late event-free survival, however, were not
      improved by routine thrombectomy with this device.

PMID- 14662268
TI  - Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left
      ventricular non-compaction.
AB  - OBJECTIVES: We evaluated the role of Cypher/ZASP in the pathogenesis of dilated
      cardiomyopathy (DCM) with or without isolated non-compaction of the left
      ventricular myocardium (INLVM). BACKGROUND: Dilated cardiomyopathy, characterized
      by left ventricular dilation and systolic dysfunction with signs of heart
      failure, is genetically transmitted in 30% to 40% of cases. Genetic heterogeneity
      has been identified with mutations in multiple cytoskeletal and sarcomeric genes
      causing the phenotype. In addition, INLVM with a hypertrophic dilated left
      ventricle, ventricular dysfunction, and deep trabeculations, is also inherited,
      and the genes identified to date differ from those causing DCM. Cypher/ZASP is a
      newly identified gene encoding a protein that is a component of the Z-line in
      both skeletal and cardiac muscle. METHODS: Diagnosis of DCM was performed by
      echocardiogram, electrocardiogram, and physical examination. In addition, levels
      of the muscular isoform of creatine kinase were measured to evaluate for skeletal
      muscle involvement. Cypher/ZASP was screened by denaturing high performance
      liquid chromatography (DHPLC) and direct deoxyribonucleic acid sequencing.
      RESULTS: We identified and screened 100 probands with left ventricular
      dysfunction. Five mutations in six probands (6% of cases) were identified in
      patients with familial or sporadic DCM or INLVM. In vitro studies showed
      cytoskeleton disarray in cells transfected with mutated Cypher/ZASP. CONCLUSIONS:
      These data suggest that mutated Cypher/ZASP can cause DCM and INLVM and identify
      a mechanistic basis.

PMID- 14662269
TI  - Creating and adopting an ACC ethical code of conduct.

PMID- 14662270
TI  - Anemia and energy depletion.

PMID- 14662273
TI  - Determining a maximum tolerated cumulative dose: dose reassignment within the
      TITE-CRM.
AB  - We present a phase I design that is a modification to the time-to-event continual
      reassessment method (TITE-CRM) by Cheung and Chappell that is useful when each
      dose actually denotes how long a drug is administered. Because of the lengthy
      duration required for subjects receiving the higher doses, we enroll each subject
      on the best estimate of the maximum tolerated cumulative dose (MTCD) as soon as
      each subject is eligible. Once each previously enrolled subject is fully
      evaluated, we update our estimate of the MTCD and modify currently enrolled
      subjects to receive the MTCD if they are currently receiving a nonoptimal dose.
      Thus, our method is adaptive both between subjects and within subjects. We show
      through simulation that our study design has excellent operating characteristics
      that are as good as the TITE-CRM while not exposing greater numbers of subjects
      to doses beyond the MTCD. Our simulations are based upon a study in bone marrow
      transplant patients that seeks to determine how many weeks of recombinant human
      keratinocyte growth factor can be administered while keeping toxicity rates below
      a desired threshold.

PMID- 14662274
TI  - On the use and utility of the Weibull model in the analysis of survival data.
AB  - In the analysis of survival data arising in clinical trials, Cox's proportional
      hazards regression model (or equivalently in the case of two treatment groups,
      the log-rank test) is firmly established as the accepted, statistical norm. The
      wide popularity of this model stems largely from extensive experience in its
      application and the fact that it is distribution free-no assumption has to be
      made about the underlying distribution of survival times to make inferences about
      relative death rates. However, if the distribution of survival times can be well
      approximated, parametric failure-time analyses can be useful, allowing a wider
      set of inferences to be made. The Weibull distribution is unique in that it is
      the only one that is simultaneously both proportional and accelerated so that
      both relative event rates and relative extension in survival time can be
      estimated, the latter being of clear clinical relevance. The aim of this paper is
      to examine the use and utility of the Weibull model in the analysis of survival
      data from clinical trials and, in doing so, illustrate the practical benefits of
      a Weibull-based analysis.

PMID- 14662275
TI  - Web-based decision support for clinical trial eligibility determination in an
      international clinical trials network.
AB  - Matching individuals to multisite cooperative clinical trials can be a complex
      and nonintuitive decision process that expends considerable time and may be prone
      to errors. We developed and tested a web-based decision support tool to aid
      investigators in matching patients to open clinical trials for children with
      rhabdomyosarcoma in the context of an international cooperative cancer clinical
      trials network. A decision tree for trial eligibility based on eight clinical
      variables representing major disease characteristics was translated into a web
      based format. In a blinded fashion, we assessed the accuracy of the tool in
      assigning 100 randomly selected cases to the proper clinical trial. The web-based
      tool assigned patients to the proper clinical trial in all 100 randomly selected
      cases. The time needed to enter data and receive results using this tool is about
      1 minute per patient entered. It is feasible to develop a web-based tool to help
      investigators in matching patients to clinical trials. When such decisions are
      complex and nonintuitive, such tools have the potential to improve the accuracy
      of clinical trial assignment and save time.

PMID- 14662276
TI  - Use of a run-in period to decrease loss to follow-up in the Contact Lens and
      Myopia Progression (CLAMP) study.
AB  - Rigid gas permeable (RGP) contact lenses are initially less comfortable to wear
      than spectacles. In previous studies evaluating the use of RGP contact lenses to
      control myopia, more subjects randomly assigned to wear RGP contact lenses have
      been lost to follow-up than spectacle wearers. Previous rigid contact lens myopia
      control studies have lost 44% and 47% of the rigid contact lens wearers. This
      unequal loss to follow-up may compromise the results of the study, so we
      conducted a run-in period prior to randomized treatment-group assignment to
      ensure that all participants could adapt to RGP contact lens wear. We enrolled
      147 children ages 8-11 years with myopia in the run-in period. Of the 147
      subjects, 116 (78.9%) were able to wear RGP contact lenses for at least 40 hours
      per week and reported that they were "usually comfortable" or "always
      comfortable." After 3 years, no subjects were lost to follow-up. The run-in
      period greatly reduced the loss to follow-up suffered by previous RGP contact
      lens myopia progression studies and may help provide more definitive answers
      regarding myopia control with RGP contact lenses.

PMID- 14662277
TI  - Limiting loss to follow-up in a multicenter randomized trial in orthopedic
      surgery.
AB  - Even the best-designed, randomized controlled trials suffer when patients are
      lost to follow-up. Incomplete follow-up biases the results of a trial when
      patients who drop out are different from those who complete follow-up. This is
      exaggerated further when there are differential dropout rates between study
      groups. Previous randomized controlled trials in orthopedic trauma have reported
      up to 28% loss to follow-up. Only by striving to achieve a 0% loss to follow-up
      rate can we be certain that this type of bias does not affect our results. In our
      ongoing multicenter, randomized controlled trial comparing reamed and nonreamed
      intramedullary nailing of tibial shaft fractures, we have implemented several
      innovative strategies to minimize loss to follow-up. The exclusion criteria and
      consent process are designed to minimize losses. Study staff are carefully
      trained in communication and negotiation with patients. Additionally, a central
      methods center monitors all patient follow-up and aids in finding lost patients.
      Through these primary, secondary, and tertiary interventions, we have achieved
      94% complete 1-year follow-up for the first 440 patients enrolled in the trial.
      Eleven patients withdrew consent, and we are unable to locate 17 patients. We
      have successfully minimized the loss to follow-up rate in our trial by
      incorporating innovative prevention and retention strategies into its design and
      conduct. Through planning, organization, and committing time and resources to
      minimizing loss to follow-up, other orthopedic trauma trials can hope to achieve
      the same high rates of follow-up.

PMID- 14662278
TI  - Determination of vital status at the end of the DIG trial.
AB  - The Digitalis Investigation Group (DIG) trial was a randomized, double-blind
      placebo-controlled trial whose primary objective was to determine whether digoxin
      had beneficial, harmful, or no effect on total mortality in patients with heart
      failure who were in sinus rhythm and whose ejection fraction was </=0.45. The
      study was designed as a large simple trial with a large number of centers (302)
      in the United States and Canada, many of which were inexperienced in research. To
      ensure that the results of the trial would be reported accurately without
      possible bias due to missing data, the study leadership decided that no outcome
      results would be reported until the vital status at the end of the study was
      known for at least 97% of the study participants. Planning for closeout of the
      study began a year prior to the common end date of December 31, 1995 and included
      plans for obtaining vital status on December 31, 1995. Participants were given
      postcards at their final study visit to be completed and mailed on or after
      January 1, 1996. Of 5602 postcards distributed, 5070 (90.5%) were completed and
      returned. A contract search agency was hired to locate the remaining
      participants. Of the total 7788 participants entered into the DIG trial, only 97
      participants (1.2%) could not have their vital status as of December 31, 1995
      determined. It is recommended that investigators having an outcome measure with a
      common end date include plans in their protocols for obtaining their measures and
      activate those plans as early as possible during the course of the study.

PMID- 14662279
TI  - Use of a single global assessment to reduce missing data in a clinical trial with
      follow-up at one year.
AB  - We conducted a randomized controlled trial (ISRCTN96537534) to assess the effects
      of acupuncture on migraine and chronic tension headache. Patients (n=401)
      completed a diary of headache severity four times a day for 4 weeks at baseline,
      immediately following a 3-month treatment period and 1 year after randomization.
      During the trial, it appeared that dropout might be higher than expected. We
      therefore obtained a rapid global assessment of headache from participants to aid
      imputation of missing data. Patients were contacted by telephone and asked to
      rate current and baseline headache on a 0-10 scale. Use of global assessment
      reduced the number of patients from whom we obtained no follow-up headache data
      from 69 (17%) to 24 (6%). Analysis of patients who provided both a diary and a
      global assessment demonstrated excellent properties of global assessment, with
      very similar results to the full diary. We therefore used the global assessment
      to help impute missing 1-year diary scores. Rapid global assessment can be easily
      implemented in any trial and aids imputation of missing data, though it should
      not be used instead of more intensive methods of assessment. Further research
      might usefully examine the value of global assessment for imputation of missing
      data in a variety of different settings.

PMID- 14662280
TI  - An international multicenter protocol to assess the single and combined benefits
      of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2
      factorial design (IMPACT).
AB  - For various diseases clinicians have to combine different drugs or interventions
      when a single drug or intervention does not lead to satisfactory results.
      However, quantifying the relative benefit of certain drugs or interventions when
      given alone and in combination under controlled conditions requires a complex
      factorial design. This paper describes such a method applied to a large
      multicenter trial for the prevention of postoperative nausea and vomiting (PONV),
      which may be of great interest for other specialties. Approximately 28 million
      operations are performed annually in the United States, mainly under general
      anesthesia with volatile anesthetics. Unfortunately, one-third of these patients
      suffer from PONV. This prompted extensive research of antiemetic and anesthetic
      drugs, but none of the interventions appeared to satisfactorily prevent PONV.
      Scuderi et al. were the first to almost eliminate PONV by combining various
      antiemetic interventions; however, the relative benefit of each intervention
      remained unclear. Accordingly, we have designed a large randomized controlled
      trial studying six different antiemetic interventions-three involving use of
      various antiemetic drugs and three involving choice of anesthetic drugs-to answer
      the following main questions: (1) What is the relative benefit of each of the
      antiemetic intervention? (2) Are certain combinations of antiemetic interventions
      more effective than others? Using a complete factorial design this leads to
      2(3)=8 antiemetic combinations, which multiply with the 2(3)=8 combinations of
      anesthetic drugs, leading to a total of 2(6)=64 possible combinations. The six
      factors are the antiemetics ondansetron (versus control), dexamethasone (versus
      control), droperidol (versus control), and the intravenous anesthetic propofol
      (versus volatile anesthetics), air (versus nitrous oxide), and remifentanil
      (versus fentanyl). The primary outcome is freedom from PONV within the first 24
      hours after anesthesia. Eligible patients are adults scheduled for elective
      surgery under general anesthesia with an increased risk for PONV so that the
      expected incidence in the control group (with none of the six antiemetic
      interventions) is approximately 60%. In order to allow analyses for up to three
      factor interactions, a sample size was estimated to be in the range of
      approximately 5000 patients. To the best of our knowledge this is the first
      randomized controlled trial of a six-way factorial design that may serve as an
      example for numerous other medical specialties.

PMID- 14662281
TI  - The Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study: design
      and baseline characteristics.
AB  - The Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) trial is a
      three-arm, randomized, placebo-controlled, double-blind study to determine the
      effect of tibolone 2.5 mg (Org OD 14) and continuous combined conjugated equine
      estrogens plus medroxyprogesterone acetate (0.625 mg/2.5 mg respectively) on
      progression of intima-media thickness of the carotid arteries and bone mineral
      density of the lumbar vertebrae and proximal femur in postmenopausal women. A
      total of 866 healthy postmenopausal women were recruited in six U.S. centers and
      five European centers. Duplicate carotid ultrasound examinations of the common
      carotid artery, the carotid bifurcation, and the internal carotid artery were
      performed at baseline. Single measurements of bone mineral density of the lumbar
      vertebrae and proximal femur were obtained at baseline. After randomization,
      ultrasound examinations were repeated every 6 months for 36 months following
      baseline, with a duplicate examination at the end of the study. Bone mineral
      density was measured every 12 months throughout the trial. The primary outcome is
      change in mean common carotid intima-media thickness (CIMT), defined as the
      average of the intima-media thickness measurements performed circumferentially at
      predefined angles for the near and far wall of 10-mm segments of the right and
      left distal common carotid arteries. Unique new features of the OPAL study are
      the specifically developed OPAL ultrasound protocol, yielding highly reproducible
      CIMT measurements, and the use of two experienced core laboratories for CIMT
      readings (one in the United States and one in Europe) with one common quality
      assurance and control program. The OPAL study is a large, placebo-controlled
      trial evaluating the effects of tibolone, as well as one of the first large
      randomized studies to determine the effects of continuous combined estrogen
      progestin therapy on carotid atherosclerosis in healthy postmenopausal women. The
      OPAL study results are expected to complement other studies on atherosclerosis
      progression in healthy postmenopausal women.

PMID- 14662282
TI  - Evaluation of outcome and cost-effectiveness using an FDG PET-guided approach to
      management of patients with coronary disease and severe left ventricular
      dysfunction (PARR-2): rationale, design, and methods.
AB  - Patients with severe ventricular dysfunction and coronary disease have high
      morbidity and mortality. They may benefit from revascularization but have
      significant perioperative morbidity and mortality. Positron emission tomography
      (PET) imaging with F-18-fluorodeoxyglucose (FDG) can detect viable myocardium
      that may recover from revascularization in such patients. It is unclear whether
      use of FDG PET in this population improves outcome or is cost-effective. The
      principal aim of this study is to determine whether FDG PET-guided therapy
      improves clinical outcome compared to standard care. Secondary objectives are to
      determine whether FDG PET-guided therapy improves left ventricular (LV) function,
      improves quality of life, and provides a cost benefit versus standard care.
      Included in this multicenter randomized controlled trial are patients with
      coronary artery disease and severe LV dysfunction who are referred for
      revascularization, heart failure, or cardiac transplantation or in whom FDG PET
      is potentially useful. Consenting subjects will be randomized to therapy directed
      by FDG PET or standard care. The primary outcome is the composite cardiovascular
      endpoint of cardiac death, myocardial infarction, transplantation, or
      rehospitalization for unstable angina or heart failure. Secondary outcomes
      include health-related quality of life, costs, mortality, cardiovascular events,
      and LV function. Assuming two-sided alpha=0.05, power=80%, a sample size of 206
      patients per group is required to detect a 15% absolute difference in the primary
      outcome between PET-directed therapy compared to standard care. Analyses will be
      conducted on an intention-to-treat basis. To our knowledge, this is the first
      large trial to evaluate whether FDG PET-directed therapy is effective and
      provides a cost benefit in patients with severe LV dysfunction. If so, thousands
      of such patients can be risk-stratified to select who is likely to benefit from
      revascularization.

PMID- 14662283
TI  - The Children's Amalgam Trial: design and methods.
AB  - The safety of silver amalgam as a dental restorative material has been
      controversial since its introduction 150 years ago, but until recently it has
      been assumed that the exposure to mercury from dental amalgam is limited to the
      acute placement phase. However, some recent studies have raised safety concerns
      by demonstrating chronic release of mercury vapor from amalgam fillings during
      chewing and brushing. The Children's Amalgam Trial is a two-arm randomized trial
      of safety, comparing amalgam with a mercury-free restorative material. A single
      masking procedure is used to ensure that all investigators and staff measuring
      outcomes are unaware of assigned trial arm. The study follows 534 New England
      children, aged 6-10 years at enrollment, for 5 years. The children were recruited
      from two northeastern U.S. communities, one in rural Maine and one in urban
      Massachusetts. No trial subjects received prior amalgam restorations, and all
      were in need of at least two posterior occlusal fillings. Participants were
      randomized to receive either amalgam or composite material for all posterior
      restorations at baseline and at subsequent visits. The primary endpoint will be 5
      year change in IQ scores. Secondary endpoints will include measures of other
      neuropsychological assessments and renal functioning. This paper describes the
      design of the Children's Amalgam Trial and includes data on baseline
      characteristics of the subjects.

PMID- 14662284
TI  - The Italian-American Clinical Trial of Nutritional Supplements and Age-Related
      Cataract (CTNS): design implications. CTNS report no. 1.
AB  - The Italian-American Clinical Trial of Nutritional Supplements and Age-Related
      Cataract (CTNS) is a 13-year study designed primarily to evaluate the safety and
      efficacy of a vitamin-mineral supplement containing recommended daily allowance
      (RDA) dosages in preventing age-related cataract or delaying its progression. As
      secondary objectives the study will collect data on incidence and progression
      rates as well as risk factors for the disease. The clinical trial was initiated
      largely because of epidemiological studies suggesting that various nutrients,
      particularly those with antioxidant capabilities, might retard cataract
      development. The possibility of a beneficial effect on cataract and other age
      related diseases has contributed to the widespread use of dietary supplements in
      the United States among the elderly population, even in the absence of definitive
      evidence about the safety and effectiveness of such use. The low rate of dietary
      supplement use in the Italian population provided an opportunity for a trial in
      which the efficacy of RDA dose supplementation could be tested against no
      supplementation at all. Relevant design issues for the study include defining
      cataract and cataract progression, estimating event rates, evaluating
      reproducibility of the lens grading system for different types of opacity, and
      identifying the criteria for assessing efficacy and safety. This paper describes
      the CTNS design and rationale and the approach used to address the issues
      described above.

PMID- 14662286
TI  - Function of marine organisms - mechanisms of adaptation to diverse environments.
      Proceedings from an international symposium. Tokyo, Japan. February 22-23, 2003.

PMID- 14662287
TI  - Protein adaptations to temperature and pressure: complementary roles of adaptive
      changes in amino acid sequence and internal milieu.
AB  - Retention of required structural and functional properties of proteins in species
      adapted to different temperatures and pressures is achieved through variation in
      amino acid sequence and accumulation of small organic solutes that stabilize
      protein traits. Conservation of ligand binding and catalytic rate can be achieved
      by minor differences in sequence. For orthologs of lactate dehydrogenase-A (A(4)
      LDH) temperature adaptation may involve only a single amino acid substitution.
      Adaptation involves changes in conformational mobility of regions of A(4)-LDH
      that undergo movement during ligand binding, movements that are rate-limiting to
      catalysis. A model that integrates adaptations in sequence and intracellular
      milieu is developed on the basis of conformational microstates. Although
      orthologs of different thermally adapted species vary in stability, at
      physiological temperatures it is hypothesized that a similar ensemble of
      conformational microstates exists for all orthologs. Organic solutes stabilize
      this ensemble of microstates. Differences among orthologs in responses to organic
      solutes at a common temperature lead to similar responses at normal body
      temperatures. Because protein stability increases at high protein concentrations,
      intrinsic stabilities of proteins may reflect the protein concentrations of the
      cellular compartments in which they occur. Protein-stabilizing solutes like
      trimethylamine-N-oxide (TMAO) conserve protein function and structure at elevated
      hydrostatic pressures.

PMID- 14662288
TI  - Molecular biology of major components of chloride cells.
AB  - Current understanding of chloride cells (CCs) is briefly reviewed with emphasis
      on molecular aspects of their channels, transporters and regulators. Seawater
      type and freshwater-type CCs have been identified based on their shape, location
      and response to different ionic conditions. Among the freshwater-type CCs,
      subpopulations are emerging that are implicated in the uptake of Na(+), Cl(-) and
      Ca(2+), respectively, and can be distinguished by their shape of apical crypt and
      affinity for lectins. The major function of the seawater CC is transcellular
      secretion of Cl(-), which is accomplished by four major channels and
      transporters: (1). CFTR Cl(-) channel, (2). Na(+),K(+)-ATPase, (3).
      Na(+)/K(+)/2Cl(-) cotransporter and (4). a K(+) channel. The first three
      components have been cloned and characterized, but concerning the K(+) channel
      that is essential for the continued generation of the driving force by Na(+),K(+)
      ATPase, only one candidate is identified. Although controversial, freshwater CCs
      seem to perform the uptake of Na(+), Cl(-) and Ca(2+) in a manner analogous to
      but slightly different from that seen in the absorptive epithelia of mammalian
      kidney and intestine since freshwater CCs face larger concentration gradients
      than ordinary epithelial cells. The components involved in these processes are
      beginning to be cloned, but their CC localization remains to be established
      definitively. The most important yet controversial issue is the mechanism of
      Na(+) uptake. Two models have been postulated: (i). the original one involves
      amiloride-sensitive electroneutral Na(+)/H(+) exchanger (NHE) with the driving
      force generated by Na(+),K(+)-ATPase and carbonic anhydrase (CA) and (ii). the
      current model suggests that Na(+) uptake occurs through an amiloride-sensitive
      epithelial sodium channel (ENaC) electrogenically coupled to H(+)-ATPase. While
      fish ENaC remains to be identified by molecular cloning and database mining, fish
      NHE has been cloned and shown to be highly expressed on the apical membrane of
      CCs, reviving the original model. The CC is also involved in acid-base
      regulation. Analysis using Osorezan dace (Tribolodon hakonensis) living in a pH
      3.5 lake demonstrated marked inductions of Na(+),K(+)-ATPase, CA-II, NHE3,
      Na(+)/HCO(3)(-) cotransporter-1 and aquaporin-3 in the CCs on acidification,
      leading to a working hypothesis for the mechanism of Na(+) retention and acid
      base regulation.

PMID- 14662289
TI  - Water metabolism in the eel acclimated to sea water: from mouth to intestine.
AB  - Eels seem to be a suitable model system for analysing regulatory mechanisms of
      drinking behavior in vertebrates, since most dipsogens and antidipsogens in
      mammals influence the drinking rate in the seawater eels similarly. The drinking
      behavior in fishes consists of swallowing alone, since they live in water and
      water is constantly held in the mouth for respiration. Therefore, contraction of
      the upper esophageal sphincter (UES) muscle limits the drinking rate in fishes.
      The UES of the eel was innervated by the glossopharyngeal-vagal motor complex
      (GVC) in the medulla oblongata (MO). The GVC neurons were immunoreactive to an
      antibody raised against choline acetyltransferase (ChAT), an acetylcholine (ACh)
      synthesizing enzyme, indicating that the eel UES muscle is controlled
      cholinergically by the GVC. The neuronal activity of the GVC was inhibited by
      adrenaline or dopamine, suggesting catecholaminergic innervation to the GVC. The
      AP and the commissural nucleus of Cajal (NCC) in the MO projected to the GVC and
      were immunoreactive to an antibody raised against tyrosine hydroxylase (TH), rate
      limiting enzyme to produce catecholamines from tyrosine. Therefore, it is likely
      that activation in the AP or the NCC may inhibit the GVC and thus relaxes the UES
      muscle, which allows for water to enter into the esophagus. During passing
      through the esophagus, the imbibed sea water (SW) was desalted to approximately
      1/2 SW, which was further diluted in the stomach and arrived at the intestine as
      approximately 1/3 SW, almost isotonic to the plasma. Finally, from the diluted
      SW, the eel intestine absorbed water following the Na(+)-K(+)-2Cl(-) cotransport
      (NKCC2) system. The NaCl and water absorption across the intestine was regulated
      by various factors, especially by peptides such as atrial natriuretic peptide
      (ANP) and somatostatin (SS-25 II). During desalination in the esophagus, however,
      excess salt enters into the blood circulation, which is liable to raise the
      plasma osmolarity. However, the eel heart was constricted powerfully by the
      hyperosmolarity, suggesting that the hyperosmolarity enhances the stroke volume
      to the gill, where excess salt was extruded powerfully via Na(+)-K(+)-2Cl(-)
      cotransport (NKCC1) system.

PMID- 14662290
TI  - Asian medaka fishes offer new models for studying mechanisms of seawater
      adaptation.
AB  - Japanese medaka (Oryzias latipes) is a freshwater (FW) teleost that is popular
      throughout the world for laboratory use. In this paper, we discuss the utility of
      Japanese medaka and related species for studying mechanisms of seawater (SW)
      adaptation. In addition to general advantages as an experimental animal such as
      their daily spawning activity, transparency of embryos, short generation time and
      established transgenic techniques, Japanese medaka have some adaptability to SW
      unlike the strictly stenohaline zebrafish (Danio rerio). Since other species in
      the genus Oryzias exhibit different degrees of adaptability to SW, comparative
      studies between Japanese medaka, where molecular-biological and genetic
      information is abundant, and other Oryzias species are expected to present
      varying approaches to solving the problems of SW adaptation. We introduce some
      examples of interspecies comparison for SW adaptabilities both in adult fish and
      in embryos. Oryzias species are good models for evolutionary, ecological and
      zoogeographical studies and a relationship between SW adaptability and geographic
      distribution has been suggested. Medaka fishes may thus deliver new insights into
      our understanding of how fish have expanded their distribution to a wide variety
      of osmotic environments.

PMID- 14662291
TI  - Effects of transfer from seawater to fresh water on the growth hormone/insulin
      like growth factor-I axis and prolactin in the Tilapia, Oreochromis mossambicus.
AB  - The effect of freshwater (FW) transfer on growth and on the growth hormone
      (GH)/insulin-like growth factor-I (IGF-I) axis was examined in the tilapia,
      Oreochromis mossambicus. Tilapia were raised in seawater (SW) for 5 months and
      then transferred to FW for an additional 40 days. The growth rate of the fish
      transferred to FW was significantly reduced compared with the growth rate of fish
      that remained in SW. Plasma levels of GH were significantly elevated in FW
      transferred fish, as were plasma IGF-I levels. Pituitary GH and liver IGF-I mRNA
      levels, on the other hand, were significantly reduced in the fish transferred to
      FW. There was a significant correlation between body mass and mRNA levels of GH
      and IGF-I, but not with plasma levels of GH and IGF-I. Fish transferred to FW had
      significantly higher prolactin (PRL)(177) levels than the SW control fish,
      although there was no difference in plasma PRL(188) levels. Consistent with the
      hyperosmoregulatory effects of PRL, mRNA levels of both PRL(177) and PRL(188)
      were significantly higher in FW-transferred fish than in the fish in SW. These
      results suggest that transferring tilapia from SW to FW activates the GH/IGF-I
      axis, but growth is still inhibited, possibly due to the greater metabolic cost
      of osmoregulation in FW than in SW.

PMID- 14662292
TI  - Effects of environmental salinity and 17alpha-methyltestosterone on growth and
      oxygen consumption in the tilapia, Oreochromis mossambicus.
AB  - Effects of environmental salinity and 17alpha-methyltestosterone (MT) on growth
      and oxygen consumption were examined in the tilapia, Oreochromis mossambicus.
      Yolk-sac fry were collected from brood stock in fresh water (FW). After yolk-sac
      absorption, they were assigned randomly to one of four groups: FW, MT treatment
      in FW, seawater (SW) and MT treatment in SW. All treatment groups were fed to
      satiation three times daily. The fish reared in SW (both control and MT-treated
      groups) grew significantly larger than either group in FW from day 43 throughout
      the experiment (195 days). The fish fed with MT added to their feed grew
      significantly larger than their respective controls from day 85 in FW and in SW
      until the end of the experiment. The routine metabolic rate (RMR) was determined
      monthly from month 2 (day 62) to month 5 (day 155). A significant negative
      correlation was seen between RMR and body mass in all treatment groups. Among
      fish of the same age, the SW-reared tilapia had significantly lower RMRs than the
      FW-reared fish. The MT-treated fish in SW showed significantly lower RMRs than
      the SW control group at months 3-5, whereas MT treatment in FW significantly
      increased the RMR at month 3. Comparison of regression lines between RMR and body
      mass indicates that MT treatment in FW caused a significant increase in oxygen
      consumption at a given mass of the fish, whereas MT treatment was without effect
      on RMR in SW-reared fish. These results clearly indicate that SW-rearing and MT
      treatment accelerate growth of tilapia, and that RMR decreases as fish size
      increased. It is also likely that the increased RMR and growth in MT-treated
      tilapia in FW may be due to the metabolic actions of MT, although the reason for
      the absence of MT treatment in SW is unclear.

PMID- 14662293
TI  - Pulsatile urea excretion in the gulf toadfish: mechanisms and controls.
AB  - Opsanus beta expresses a full complement of ornithine-urea cycle (OUC) enzymes
      and is facultatively ureotelic, reducing ammonia-N excretion and maintaining urea
      N excretion under conditions of crowding/confinement. The switch to ureotelism is
      keyed by a modest rise in cortisol associated with a substantial increase in
      cytosolic glutamine synthetase for trapping of ammonia-N and an upregulation of
      the capacity of the mitochondrial OUC to use glutamine-N. The entire day's urea-N
      production is excreted in 1 or 2 short-lasting pulses, which occur exclusively
      through the gills. The pulse event is not triggered by an internal urea-N
      threshold, is not due to pulsatile urea-N production, but reflects pulsatile
      activation of a specific branchial excretion mechanism that rapidly clears urea-N
      from the body fluids. A bidirectional facilitated diffusion transporter, with
      pharmacological similarity to the UT-A type transporters of the mammalian kidney,
      is activated in the gills, associated with an increased trafficking of dense
      cored vesicles in the pavement cells. An 1814 kB cDNA ('tUT') coding for a 475
      amino acid protein with approximately 62% homology to mammalian UT-A's has been
      cloned and facilitates phloretin-sensitive urea transport when expressed in
      Xenopus oocytes. tUT occurs only in gill tissue, but tUT mRNA levels do not
      change over the pulse cycle, suggesting that tUT regulation occurs at a level
      beyond mRNA. Circulating cortisol levels consistently decline prior to a pulse
      event and rise thereafter. When cortisol is experimentally clamped at high
      levels, natural pulse events are suppressed in size but not in frequency, an
      effect mediated through glucocorticoid receptors. The cortisol decline appears to
      be permissive, rather than the actual trigger of the pulse event. Fluctuations in
      circulating AVT levels do not correlate with pulses; and injections of AVT (at
      supraphysiological levels) elicit only minute urea-N pulses. However, circulating
      5-hydroxytryptamine (5-HT) levels fluctuate considerably and physiological doses
      of 5-HT cause large urea-N pulse events. When the efferent cranial nerves to the
      gills are sectioned, natural urea pulse events persist, suggesting that direct
      motor output from the CNS to the gill is not the proximate control.

PMID- 14662294
TI  - Urea based osmoregulation and endocrine control in elasmobranch fish with special
      reference to euryhalinity.
AB  - Since the landmark contributions of Homer Smith and co-workers in the 1930s there
      has been a considerable advance in our knowledge regarding the osmoregulatory
      strategy of elasmobranch fish. Smith recognised that urea was retained in the
      body fluids as part of the 'osmoregulatory ballast' of elasmobranch fish so that
      body fluid osmolality is raised to a level that is iso- or slightly hyper-osmotic
      to that of the surrounding medium. From studies at that time he also postulated
      that many marine dwelling elasmobranchs were not capable of adaptation to dilute
      environments. However, more recent investigations have demonstrated that, at
      least in some species, this may not be the case. Gradual acclimation of marine
      dwelling elasmobranchs to varying environmental salinities under laboratory
      conditions has demonstrated that these fish do have the capacity to acclimate to
      changes in salinity through independent regulation of Na(+), Cl(-) and urea
      levels. This suggests that many of the presumed stenohaline marine elasmobranchs
      could in fact be described as partially euryhaline. The contributions of Thomas
      Thorson in the 1970s demonstrated the osmoregulatory strategy of a fully
      euryhaline elasmobranch, the bull shark, Carcharhinus leucas, and more recent
      investigations have examined the mechanisms behind this strategy in the
      euryhaline elasmobranch, Dasyatis sabina. Both partially euryhaline and fully
      euryhaline species utilise the same physiological processes to control urea,
      Na(+) and Cl(-) levels within the body fluids. The role of the gills, kidney,
      liver, rectal gland and drinking process is discussed in relation to the
      endocrine control of urea, Na(+) and Cl(-) levels as elasmobranchs acclimate to
      different environmental salinities.

PMID- 14662295
TI  - Muscle metabolism and growth in Antarctic fishes (suborder Notothenioidei):
      evolution in a cold environment.
AB  - The radiation of notothenioid fishes (order Perciformes) in the Southern Ocean
      provides a model system for investigating evolution and adaptation to a low
      temperature environment. The Notothenioid fishes comprising eight families, 43
      genera and 122 species dominate the fish fauna in Antarctica. The diversification
      of the clade probably began 15-20 million years ago after the formation of the
      Antarctic Polar Front. The radiation was, therefore, associated with climatic
      cooling down to the present day temperature of -1.86 degrees C. Origins and
      Evolution of the Antarctic Biota Geological Society Special Publication No. 47,
      Geological Society of London. pp. 253-268). The success of the group has been
      closely linked with the evolution of glycopeptide and peptide antifreezes, which
      are amongst the most abundant proteins in blood and interstitial fluid. The
      radiation of the clade has been associated with disaptation (evolutionary loss of
      function) and recovery. For example, it is thought that the icefishes
      (Channichyidae) lost haemoglobin through a single mutational event leading to the
      deletion of the entire beta-globin gene and the 5' end of the linked alpha-globin
      gene, resulting in compensatory adaptations of the cardiovascular system.
      Phylogenetically based statistical methods also indicate a progressive and
      dramatic reduction in the number of skeletal muscle fibres (FN(max)) at the end
      of the recruitment phase of growth in basal compared to derived families. The
      reduction in FN(max) is associated with a compensatory increase in the maximum
      fibre diameter, which can reach 100 microm in slow and 600 microm in fast muscle
      fibres. At -1 to 0 degrees C, the oxygen consumption of isolated mitochondria per
      mg mitochondrial protein shows no evidence of up-regulation relative to
      mitochondria from temperate and tropical Perciform fishes. The mitochondria
      content of slow muscle fibres in Antarctic notothenioids is towards the upper end
      of the range reported for teleosts with similar lifestyles, reaching 50% in
      Channichthyids. High mitochondrial densities facilitate ATP production and oxygen
      diffusion through the membrane lipid compartment of the fibre. Modelling studies
      suggest that adequate oxygen flux in the large diameter muscle fibres of
      notothenioids is possible because of the reduced metabolic demand and enhanced
      solubility of oxygen associated with low temperature. At the whole animal level
      size-corrected resting metabolic rate fits on the same temperature relationship
      as for Perciformes from warmer climates. It seems likely that the additional
      energetic costs associated with antifreeze synthesis and high mitochondrial
      densities are compensated for by reductions in other energy requiring processes:
      a hypothesis that could be tested with detailed energy budget studies. One
      plausible candidate is a reduction in membrane leak pathways linked to the loss
      of muscle fibres, which would serve to minimise the cost of maintaining ionic
      gradients.

PMID- 14662296
TI  - The molecular mechanisms of life history alterations in a rotifer: a novel
      approach in population dynamics.
AB  - The rotifer Brachionus plicatilis is a widely-used model for population dynamics
      studies. During the population growth of B. plicatilis, life history parameters
      such as reproduction and lifespan change widely, and determine the balance
      between birth and death rates that regulates the population fluctuations. The
      lifespan of B. plicatilis was extended 30% by inhibiting a phosphatidylinositol-3
      OH kinase involved in an insulin/insulin-like growth factor (IGF) signal
      transduction pathway that regulates the reproduction and lifespan in nematodes.
      Subsequently, we cloned a cDNA encoding Mn-superoxide dismutase (SOD), which may
      function downstream of the IGF pathway. Real-time reverse-transcription
      polymerase chain reaction analysis revealed that the expression level of Mn-SOD
      mRNA was higher in B. plicatilis with longer lifespans than those with shorter
      lifespans. In addition, stress proteins may also influence population dynamics as
      molecules regulating lifespan and molecular chaperones to maintain the cellular
      integrity. Accordingly, we cloned two stress protein genes encoding HSP70 and
      GRP94, and found that their expression changed during the population growth of
      rotifers. Thus, this novel approach of integrating population ecology and
      molecular biology has potential use in investigation the detailed mechanisms of
      rotifer population dynamics.

PMID- 14662297
TI  - Molecular diversity of skin mucus lectins in fish.
AB  - Among lectins in the skin mucus of fish, primary structures of four different
      types of lectin have been determined. Congerin from the conger eel Conger
      myriaster and AJL-1 from the Japanese eel Anguilla japonica were identified as
      galectin, characterized by its specific binding to beta-galactoside. Eel has
      additionally a unique lectin, AJL-2, which has a highly conserved sequence of C
      type lectins but displays Ca(2+)-independent activity. This is rational because
      the lectin exerts its function on the cutaneous surface, which is exposed to a
      Ca(2+) scarce environment when the eel is in fresh water. The third type lectin
      is pufflectin, a mannose specific lectin in the skin mucus of pufferfish Takifugu
      rubripes. This lectin showed no sequence similarity with any known animal lectins
      but, surprisingly, shares sequence homology with mannose-binding lectins of
      monocotyledonous plants. The fourth lectin was found in the ponyfish Leiognathus
      nuchalis and exhibits homology with rhamnose-binding lectins known in eggs of
      some fish species. These lectins, except ponyfish lectin, showed agglutination of
      certain bacteria. In addition, pufflectin was found to bind to a parasitic
      trematode, Heterobothrium okamotoi. Taken together, these results demonstrate
      that skin mucus lectins in fish have wide molecular diversity.

PMID- 14662298
TI  - Apoptosis in zebrafish development.
AB  - Apoptosis (programmed cell death) is important in normal biological processes and
      in pathogenesis in vertebrates. This review focuses on some of the prominent
      features of apoptosis during fish development. Caspases and other apoptosis
      regulating genes have been cloned from zebrafish (Danio rerio) and other fish
      species. Elucidation of in vivo functions of apoptosis is focused on development,
      morphogenesis and sex differentiation. In an attempt to elucidate cause and
      effect relationships between caspase and development, transgenic zebrafish
      overexpressing procaspase-3 were generated. Stress-induced apoptosis in zebrafish
      embryos can be monitored by whole mount TUNEL staining and caspase assay. Thus,
      zebrafish is a useful experimental model animal for investigation of apoptosis in
      vivo.

PMID- 14662299
TI  - Regulation of CaCO(3) formation in coccolithophores.
AB  - Coccolithophores impact the ocean carbon cycle principally through the generation
      of CO(2) during CaCO(3) production. Coccolithophore biomineralization has been
      examined most extensively in Pleurochrysis carterae and Emiliania huxleyi both of
      which produce mineralized scales-coccoliths-composed of elaborate calcite
      crystals attached to an underlying organic base plate. Calcification of preformed
      base plates is mediated by acidic polysaccharides and occurs in Golgi-derived
      structures known as mineralizing vesicles. In Pleurochrysis a high capacity
      calcium-binding polysaccharide PS2 is required for efficient nucleation of
      calcitic protocrystals. A galacturonomannan PS3 is required for the growth and
      transformation of the protocrystals into a massive double disc of calcite. The
      genes that regulate expression of the glycans have not yet been identified. In
      addition to the coccolith-bearing diploid phases, Pleurochrysis and Emiliania
      possess both haploid and diploid non-calcifying stages, which are self
      perpetuating via binary fission. One non-calcifying Pleurochrysis phase fails to
      synthesis PS2 and spontaneously reverts to the mineralizing morphotype in
      laboratory cultures. As yet, there is little information on environmental factors
      that effect the expression or silencing of calcifying genes or favor the growth
      of calcifying over non-calcifying phases. These issues will need extensive
      investigation, if we are to appreciate the role of coccolithophores in the
      regulation of atmospheric CO(2) levels.

PMID- 14662300
TI  - Cloning and expression of a cDNA encoding a matrix peptide associated with
      calcification in the exoskeleton of the crayfish.
AB  - Calcification-associated peptide (CAP)-1 isolated from the exoskeleton of the
      crayfish, Procambarus clarkii, has anti-calcification activity and chitin-binding
      ability and is, therefore, considered to be associated with calcification. In
      this study, a cDNA encoding CAP-1 was cloned and characterized. An open reading
      frame encoded a pre-propeptide of 99 amino acid residues, which was composed of a
      signal peptide, a CAP-1 precursor and two-basic amino acid residues at the C
      terminus. The dibasic residues were not observed in the natural CAP-1. Expression
      analyses using Northern blot and RT-PCR revealed that the mRNA encoding CAP-1 was
      strongly expressed in the epidermal tissue during the postmolt stage, where and
      when the calcification takes place. These results support that CAP-1 may play an
      important role in the calcification of the exoskeleton. Based on the nucleotide
      sequence of the cDNA encoding CAP-1, a recombinant CAP-1 and that carrying the
      basic residues at the C-terminus were expressed in Escherichia coli. Anti
      calcification assay showed that these recombinant peptides were less active than
      natural CAP-1, indicating that the phosphate group at the 70th residue, Ser, in
      natural CAP-1 is important for inhibitory activity and that the paired basic
      residues have some contribution to the elevation of inhibitory activity.

PMID- 14662301
TI  - Molecular analyses of protein components of the organic matrix in the exoskeleton
      of two scleractinian coral species.
AB  - Biochemical and histological studies on the exoskeleton of scleractinian corals
      had demonstrated presence of the organic matrix containing proteins, lipids and
      chitin. Examination at the electron microscopic level had shown that the initial
      phase of calcification occurred in close association with organic substances
      secreted by calicoblastic cells. The possibility was thereby proposed that
      certain organic substances induce formation of calcium carbonate crystals,
      presumably functioning as templates for nucleation. In search for such a
      molecule, biochemical and molecular analyses were initiated on protein components
      of the organic matrix extracted from the calcified exoskeleton of the hermatypic
      coral, Galaxea fascicularis and the ahermatype, Tubastrea aurea. In SDS-PAGE
      analyses of the extracts, one major protein and a few other minor bands were
      detected in each of the two species. A cDNA encoding the major protein (named
      galaxin) in G. fascicularis was cloned and its primary structure was deduced. It
      consisted mostly of tandem repeats of a unit sequence of about 30 residues, and
      its sequence did not exhibit significant similarity to known proteins.
      Preliminary characterization of the T. aurea proteins showed that two proteins
      bound Ca(2+), and suggested that the major protein of 46 kDa was not homologous
      to galaxin.

PMID- 14662302
TI  - Physiological regulation of carbon fixation in the photosynthesis and
      calcification of coccolithophorids.
AB  - Emiliania huxleyi and Gephyrocapsa oceanica are the predominant coccolithophorid
      species that produce blooms in the ocean and affect the global environment. These
      species are capable of carbon fixation by both photosynthesis for organic matter
      production and by intracellular calcification for coccolith production. Both
      processes were strongly affected by the nutrient status in a laboratory culture.
      The coccolith production was stimulated by the addition of a high concentration
      of sodium bicarbonate and by the depletion of phosphate. Interestingly, when the
      calcification was stimulated, the increase in cell number during algal growth was
      greatly suppressed and then the cell volume increased. When the growth rate was
      increased under nutrient-sufficient conditions, the cells became very small in
      size and most of them bore few or no coccoliths. The data from laboratory
      experiments show that the cell growth and calcification proceeded apparently
      independently at different phases. We, therefore, assume that the
      coccolithophorid blooms in the ocean might be separated into two phases; firstly,
      the increase in cell population might be triggered by an adequate supply of
      nutrients to enhance algal growth and then the calcification might subsequently
      be stimulated when the nutrients become depleted by substantial algal growth.

PMID- 14662303
TI  - Dietary protein-induced changes in excretory function: a general animal design
      feature.
AB  - Mammals are ureotelic and respond to an increased protein intake with an increase
      in glomerular filtration rate and renal plasma flow. Birds and terrestrial
      insects are uricotelic and following a high protein intake increase tubular urate
      secretion by the kidney (birds) or Malpighian tubule (insects). Ureogenic fish
      given NH(4)Cl increase gill and renal clearance of urea and gill clearance of
      ammonia. Renal mass increases in mammals, birds and reptiles given a high protein
      intake. Thus, animals in general respond to an increase in protein intake with a
      change in excretory function such as to increase the clearance of the major
      nitrogenous end-products of protein metabolism. The components of this general
      animal excretory response include; a redistribution of regional perfusion with
      increased renal and gill blood flow, increased GFR and gill ammonia clearance,
      increased renal tubular urate clearance, changes in urea transport protein
      abundance and/or function and renal hypertrophy. Animal groups differ as to which
      components are accentuated. Amino acid catabolism with generation of ammonia
      appears to be a necessary prerequisite for this excretory response to occur. A
      hypothesis is put forward that ammonia itself is a regulatory molecule and an
      important signal communicating between amino acid catabolism following an
      increase in protein intake and the sequence of events leading to a change in
      excretory function.

PMID- 14662304
TI  - Molecular cloning of three cDNAs encoding putative larval cuticle protein
      expressed differentially after larval ecdysis from the mulberry longicorn beetle,
      Apriona germari.
AB  - Three cDNAs encoding putative larval cuticle protein (LCP) were cloned from the
      mulberry longicorn beetle, Apriona germari. The three cDNA sequences were 309 bp,
      396 bp and 408 bp in length, encoding 103, 132 and 136 amino acid residues,
      respectively. The predicted molecular masses for these LCPs were approximately
      9.2 kDa (AgLCP9.2), 12.3 kDa (AgLCP12.3) and 12.6 kDa (AgLCP12.6). Pairwise
      identity among AgLCP9.2, AgLCP12.3 and AgLCP12.6 were relatively low. Each AgLCP
      contained a type-specific consensus sequence identifiable in other insect cuticle
      proteins. The deduced amino acid sequence of AgLCP9.2 is most similar to Bombyx
      mori LCP18 and those of AgLCP12.3 and AgLCP12.6 are both most similar to B. mori
      LCP17. Northern blot analysis revealed that the three AgLCPs showed epidermis
      specific expression. The expression profile of AgLCPs after larval ecdysis
      revealed by Northern blot analysis that the high-level mRNA expression of AgLCPs
      was detected on the first day of larval ecdysis for AgLCP9.2, on the fifth day
      for AgLCP12.3 and from the first day of larval ecdysis to the fifth day after
      larval ecdysis for AgLCP12.6, demonstrating that AgLCP mRNAs are differentially
      expressed in epidermis after larval ecdysis.

PMID- 14662305
TI  - Amino acids defining the acyl pocket of an invertebrate cholinesterase.
AB  - Amphioxus (Branchiostoma floridae) cholinesterase 2 (ChE2) hydrolyzes
      acetylthiocholine (AsCh) almost exclusively. We constructed a homology model of
      ChE2 on the basis of Torpedo californica acetylcholinesterase (AChE) and found
      that the acyl pocket of the enzyme resembles that of Drosophila melanogaster
      AChE, which is proposed to be comprised of Phe330 (Phe290 in T. californica AChE)
      and Phe440 (Val400), rather than Leu328 (Phe288) and Phe330 (Phe290), as in
      vertebrate AChE. In ChE2, the homologous amino acids are Phe312 (Phe290) and
      Phe422 (Val400). To determine if these amino acids define the acyl pocket of ChE2
      and its substrate specificity, and to obtain information about the hydrophobic
      subsite, partially comprised of Tyr352 (Phe330) and Phe353 (Phe331), we performed
      site-directed mutagenesis and in vitro expression. The aliphatic substitution
      mutant F312I ChE2 hydrolyzes AsCh preferentially but also butyrylthiocholine
      (BsCh), and the change in substrate specificity is due primarily to an increase
      in k(cat) for BsCh; K(m) and K(ss) are also altered. F422L and F422V produce
      enzymes that hydrolyze BsCh and AsCh equally due to an increase in k(cat) for
      BsCh and a decrease in k(cat) for AsCh. Our data suggest that Phe312 and Phe422
      define the acyl pocket. We also screened mutants for changes in sensitivity to
      various inhibitors. Y352A increases the sensitivity of ChE2 to the bulky
      inhibitor ethopropazine. Y352A decreases inhibition by BW284c51, consistent with
      its role as part of the choline-binding site. Aliphatic replacement mutations
      produce enzymes that are more sensitive to inhibition by iso-OMPA, presumably by
      increasing access to the active site serine. Y352A, F353A and F353V make ChE2
      considerably more resistant to inhibition by eserine and neostigmine, suggesting
      that binding of these aromatic inhibitors is mediated by pi-pi or cation-pi
      interactions at the hydrophobic site. Our results also provide information about
      the aromatic trapping of the active site histidine and the inactivation of ChE2
      by sulfhydryl reagents.

PMID- 14662306
TI  - Molecular cloning and expression of the turkey leptin receptor gene.
AB  - A cDNA encoding the long form of the turkey (Meleagris gallopavo) leptin receptor
      (LEPR) was cloned and sequenced. Turkey LEPR showed greater than 90% sequence
      identity at both the nucleotide and amino acid level with chicken LEPR. The LEPR
      gene (long form) encodes a protein of 1147 amino acids that has features similar
      to other LEPRs including: a signal peptide, a single transmembrane domain, and
      specific conserved motifs defining putative leptin-binding and signal
      transduction regions of the protein. In addition, a LEPR gene-related protein
      (LEPR-GRP) mRNA transcript was also identified and a portion of the corresponding
      cDNA containing the complete coding region was sequenced. The turkey LEPR-GRP
      gene encodes a 14-kDa (131 amino acids) protein that is distinct from LEPR. LEPR
      gene expression was quantified relative to beta-actin in total RNA samples
      isolated from various tissues of 3-week-old turkey poults. Expression of LEPR was
      highest in brain, spleen and lung tissue with lower levels of expression in
      kidney, pancreas, duodenum, liver, fat and breast muscle. In developing turkey
      embryos, expression of LEPR was highest in brain tissue throughout incubation
      (days 14-28). Expression of LEPR in embryonic liver tissue peaked at day 16 and
      then declined toward hatching (day 28). Yolk sac expression of LEPR declined from
      day 14 to day 20 and then increased toward hatching. Our findings clearly
      demonstrate the expression of LEPR and LEPR-GRP in different tissues during
      embryonic and post-hatch development. In conclusion, this is the first report to
      identify and characterize LEPR and LEPR-GRP gene homologues in the domestic
      turkey.

PMID- 14662307
TI  - Identification of a unique transcript down-regulated in the retina of rainbow
      trout (Oncorhynchus mykiss) at smoltification.
AB  - Developmental and physiological changes in the retina of salmonid fishes occur
      during smoltification, a metamorphic event associated with thyroid hormone that
      prepares salmon for oceanic migration. These changes include loss of ultraviolet
      sensitive (UVS) cone photoreceptors, switching of visual pigments, alterations in
      thyroid hormone regulation, and associated changes in behavior. This model
      provides an opportunity to study substantial neuronal development within an
      established retina. Little is known, however, about how higher order neurons are
      altered or how retinal gene expression changes during this transition. Here, we
      have used differential display RT-PCR and RACE-PCR to identify a previously
      uncharacterized gene transcript in Oncorhynchus mykiss under developmental
      regulation in the retina during smoltification, rtp12.5. This unique cDNA encodes
      a putative protein 112 amino acids long similar to a hypothetical human open
      reading frame located on chromosome 14.Q24.2. Differential expression was
      confirmed by RNA dot blot and in situ hybridization. We also present O. mykiss
      sep15 cDNA sequence and describe its expression in the vertebrate retina.
      Considering the expression pattern within retinal tissue observed by in situ
      hybridization, rtp12.5 may be under TH regulation and involved in neuronal
      remodeling of the retina during loss of UVS cones.

PMID- 14662308
TI  - Comparative analysis of avian BMAL1 and CLOCK protein sequences: a search for
      features associated with owl nocturnal behaviour.
AB  - Animals differ widely in the phasing of their daily rhythms with respect to daily
      environmental rhythms. While birds are predominantly day-active, nocturnal
      activity is a characteristic feature of the order Strigiformes (owls). To study
      the evolution of owl night-activity cDNA sequences encoding the circadian core
      oscillator (CCO) proteins BMAL1 and CLOCK were obtained from barn owl (Tyto
      alba). The predicted proteins showed high sequence identity with their Galliform
      homologues (BMAL1: 99%; CLOCK: 95.6%). A computer-predicted chicken BMAL1 casein
      kinase-1 phosphorylation site is absent from T. alba BMAL1, but also absent from
      homologues of other six bird species (5 orders) (night-active (n=2), day-active
      (n=4)) indicating no evolutionary association with night activity. Sequence
      differences between T. alba and Galliform CLOCK frequently involved serine and
      threonine residues suggesting potential differences in their phosphorylation. The
      length of a poly-glutamine string in the CLOCK C-terminus varied between and
      within 25 species (6 orders) examined, however, no discernible feature
      distinguishing day and night active species was found. No differences were found
      between day (n=5) and night (n=7)-active species (12 species, 6 orders) in a
      region of the PER2 protein implicated in altered rhythm phasing in humans. In
      conclusion the avian CCO components examined showed strong evolutionary
      conservation. Molecular evolution associated with owl night-activity may have
      involved alterations in the CCO relationship with 'output' genes rather than in
      the molecular structure of the CCO itself.

PMID- 14662309
TI  - Analysis of genes expressed in head kidney of common carp Cyprinus carpio L
      treated with cortisol.
AB  - We analyzed genes expressed from head kidney of common carp Cyprinus carpio L.
      treated with cortisol. The results of single-pass sequencing of expressed
      sequence tags (ESTs) from 188 clones (AU240288-AU240367, AU301120-AU301227) from
      kidney cDNA are presented. One-hundred-twenty-seven clones (67.6%) were
      completely unknown and are likely to represent newly described genes, whereas 61
      clones (32.4%) were identified based on matches to sequences in the database. The
      putative genes contain several ribosomal proteins, cytochrome oxidase subunits.
      Immune related cDNA clones identified from kidney were immunoglobulin light chain
      (n=4), FK506/rapamycin-binding protein (FKBP), CXC chemokine receptor type 4,
      complement factor B/C2-A3, peptidylprolyl isomerase (cyclophilin; Cyp)-like1,
      cyclophilin S1, heat shock-70 kDa protein-4, stress-activated protein kinase-3
      (n=2). FKBP and cyclophilin genes expressed in normal tissues (head kidney,
      spleen, liver, brain and heart). Expression of FKBP and cyclophilin genes were
      not detected in liver, brain and heart when treated with cortisol for 16 h.

PMID- 14662310
TI  - Differences in oligosaccharide pattern of a sample of polar bear colostrum and
      mid-lactation milk.
AB  - Although the concentrations of carbohydrate in the colostrum and in the mid
      lactation milk of polar bear (Ursus maritimus) were similar, the oligosaccharide
      patterns differed. The colostrum sample contained Neu5Ac(alpha2-3)Gal(beta1-4)Glc
      (3'-N-acetylneuraminyllactose), GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (A
      tetrasaccharide), Fuc(alpha1-2)Gal(beta1-4)Glc (2'-fucosyllactose) and Gal(beta1
      4)Glc (lactose). The mid-lactation milk contained Gal(alpha1-3)[Fuc(alpha1
      2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (B-pentasaccharide), GalNAc(alpha1
      3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (A-pentasaccharide), Gal(alpha1
      3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (B-tetrasaccharide), A-tetrasaccharide,
      Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc (3-fucosylisoglobotriose), Gal(alpha1
      3)Gal(beta1-4)Glc (isoglobotriose) and lactose. The dominant saccharides in the
      colostrum were 3'-N-Acetylneuraminyllactose and lactose, whereas isoglobotriose
      was the dominant saccharide in the mid-lactation milk in which lactose was only a
      minor component. Isoglobotriose, which had previously been found to be a dominant
      saccharide in mature milk from the Ezo brown bear, the Japanese black bear and
      the polar bear, was not found in the polar bear colostrum.

PMID- 14662311
TI  - Seasonal variations in the levels of polyhydroxysteroids and related glycosides
      in the digestive tissues of the starfish Patiria (Asterina) pectinifera.
AB  - Seasonal variations in the levels of polar steroids including polyhydroxylated
      steroids and related glycosides in digestive organs of the starfish Patiria
      (=Asterina) pectinifera have been studied. The concentration of polar steroids is
      related to the annual reproductive cycle of the starfish and periods of active
      feeding. Two peaks in concentrations of polar steroids in pyloric caeca and
      stomach were found, the first in winter during reorganization and the second in
      summer during intensive gametogenesis before spawning. Probable biological
      functions of polyhydroxysteroids and related glycosides are discussed. The data
      support the hypothesis these compounds are involved in digestion in the starfish.

PMID- 14662312
TI  - Distribution of apolipoprotein E among lipoprotein fractions in the lactating
      cow.
AB  - Apolipoprotein (apo) E plays a key role in regulating plasma levels of
      lipoproteins. We investigated the serum apoE concentrations in cows during
      different lactating stages by ELISA. To confirm the distribution of apoE in
      lipoprotein fractions, cow plasma was separated by gel filtration,
      ultracentrifugation and agarose gel electrophoresis. The apoE concentrations
      during early, mid- and late lactating stages in cows were significantly higher
      than that during the non-lactating stage. In lactating plasma, apoE eluted in
      high-density lipoprotein (HDL) fractions separated by gel filtration increased.
      The portion of this apoE in plasma was 49%. However, when lactating plasma was
      separated by ultracentrifugation, less then 5% apoE was recovered in the HDL
      fraction, and more apoE was recovered in the non-lipoprotein fraction (d>1.21
      g/ml, 46%). In agarose gel electrophoresis, plasma apoE was found in beta
      migrating lipoprotein, but it was not present in alpha-migrating lipoprotein. To
      purify apoE-containing particles, the HDL fraction separated by gel filtration
      was pooled and the fraction retained on Heparin-Sepharose chromatography
      collected. Cholesterol was absent from this fraction. These results suggest that
      apoE-containing particles, which increased during the lactating stage, were not
      associated with HDL particles, and that lipid-free forms were included in cow
      plasma.

PMID- 14662313
TI  - Serum estradiol-17beta and testosterone levels during silvering in wild Japanese
      eel Anguilla japonica.
AB  - To understand the changes of serum levels of sex steroids in the wild Japanese
      eel Anguilla japonica during silvering process, eels collected from the Kaoping
      River of Taiwan from August 2000 through June 2001 were examined. The
      maturational stages of female eels before and during silvering were divided into
      four stages: juvenile, sub-adult, pre-silver and silver stages based on skin
      coloration and oocyte diameter. Male eels were investigated only in the silver
      stage. Radioimmunoassays were employed to measure serum levels of estradiol
      17beta (E(2)) and testosterone (T). The mean liver mass of the female eels
      increased significantly during silvering, but the mean hepatosomatic index
      remained constant. In contrast, mean ovarian mass and gonadosomatic index
      increased significantly during silvering. Serum concentrations of E(2) in females
      increased significantly during silvering (P<0.05), while E(2) was undetectable in
      silver males. The mean serum T concentrations increased significantly in females
      (P<0.05) during silvering, with lowest mean values in the juvenile stage and
      highest mean value in the silver stage. The mean serum T level in the silver
      males was significantly lower than in silver females (P<0.05). In conclusion,
      both serum E(2) and T concentrations increased with ovarian development of wild
      Japanese eels during silvering, while serum E(2) was undetectable in the silver
      male eels. The findings support the idea that androgen, but not estrogen, plays a
      major role in silvering process of the eels in both sexes.

PMID- 14662314
TI  - Influence of selenium sources on age-related and mild heat stress-related changes
      of blood and liver glutathione redox cycle in broiler chickens (Gallus
      domesticus).
AB  - Selenium is an essential trace element that up-regulates a major component of the
      antioxidant defense mechanism by controlling the body's glutathione (GSH) pool
      and its major Se-containing antioxidant enzyme, glutathione peroxidase (GPX).
      Evidence has emerged suggesting that organic selenium, natural seleno-amino acids
      found in plants, grains and selenized yeast, maintains the antioxidant defense
      system more efficiently than inorganic selenium. Inorganic selenium is a pro
      oxidant, whereas organic selenium possesses antioxidant properties itself. As a
      pro-oxidant, inorganic selenium is not suitable for animals or humans. Therefore,
      we examined the GSH-GPX system in broiler chickens and determined that organic
      selenium was indeed more beneficial than inorganic selenium. Chickens fed the
      organic selenium as Sel-Plex, a selenized yeast, had elevated GPX activity in
      both blood and liver in a thermoneutral environment and after heat distress. More
      importantly, the ability to reduce the oxidized glutathione (GSSG to 2 GSH) was
      enhanced and facilitated by maintenance of glutathione reductase activity.
      Organic selenium-fed chickens were less affected by mild heat distress than
      inorganic selenium-fed chickens, and this assessment was based upon less
      induction of heat shock protein 70 (hsp70) in organic selenium-fed chickens. Our
      results clearly show that heat distress, a potent inducer of oxidative stress and
      hsp70, can be partially ameliorated by feeding organic selenium. We attribute
      this observation to an enhanced GSH-GPX antioxidant system in organic selenium
      fed chickens.

PMID- 14662315
TI  - Purification and properties of an aminopeptidase from the mid-gut gland of
      scallop (Patinopecten yessoensis).
AB  - An aminopeptidase was isolated from the mid-gut gland of Patinopecten yessoensis.
      The enzyme was purified from an acetone-dried preparation by extracting, ammonium
      sulfate precipitation, Hi-Load Q column chromatography, isoelectric focusing, and
      POROS HP2 and HQ column chromatography. The molecular weight of the enzyme was
      estimated to be 61 kDa by SDS-polyacrylamide gel electrophoresis and 59 kDa by
      gel permeation chromatography. The isoelectric point of the enzyme was 5.2 and
      the optimum pH was 7.0 toward leucine p-nitroanilide (Leu-pNA). The enzyme was
      inhibited by o-phenanthroline. The activity of the enzyme treated with o
      phenanthroline was completely recovered by adding excess Zn(2+). Relative
      hydrolysis rates of amino acid-pNAs and amino acid-4-methylcoumaryl-7-amides
      (amino acid-MCAs) indicated that the enzyme preferred substrates having Ala or
      Met as an amino acid residue. The enzyme had a K(m) of 32.2 microM and k(cat) of
      29.5 s(-1) with Ala-pNA and a K(m) of 11.1 microM and k(cat) of 9.49 s(-1) with
      Ala-MCA. The enzyme sequentially liberated amino acids from the amino-termini of
      Ala-Phe-Tyr-Glu.

PMID- 14662316
TI  - Cloning of bovine peroxiredoxins-gene expression in bovine tissues and amino acid
      sequence comparison with rat, mouse and primate peroxiredoxins.
AB  - The peroxiredoxin (PRDX) family is a recently identified family of peroxidases
      found in organisms ranging from bacteria to mammals. In mammals, six PRDX
      isoforms have been characterized in human (Homo sapiens), rat (Rattus norvegicus)
      and mouse (Mus musculus). PRDXs are cytosolic, secreted or targeted to organelles
      such as peroxisomes, mitochondria and the nucleus. Some PRDXs are synthesized as
      larger precursor proteins with a presequence that is cleaved to produce the
      mature form. To study the expression of the six PRDXs in bovine (Bos taurus), we
      first cloned cDNAs coding for PRDX1, PRDX2, PRDX4 and PRDX5. PRDX3 and PRDX6 had
      previously been cloned and characterized in bovine. The comparison of bovine
      PRDXs with their rat, mouse and primate orthologues reveals a minimum of 95%
      similarity of mature proteins. Even though mitochondrial or export signal
      presequences are normally less conserved, the unprocessed proteins still present
      a minimum of 84% similarity. Nevertheless, a major divergence lies at the N
      terminus of bovine PRDX2, where a Cys-Val-Cys motif was identified. The
      expression of the six PRDXs in 22 bovine tissues has been studied by RT-PCR. Our
      results point out the ubiquity of the different PRDX transcripts in bovine
      tissues. The important conservation of the different PRDXs, the multiple
      processes they have been associated with, as well as the ubiquity of all the
      members of the family analyzed in this study for the first time altogether,
      suggest that they play a major role in the basal metabolism of mammalian cells.

PMID- 14662317
TI  - Quantification of three steroid hormone receptors of the leopard gecko
      (Eublepharis macularius), a lizard with temperature-dependent sex determination:
      their tissue distributions and the effect of environmental change on their
      expressions.
AB  - Sex steroid hormones play a central role in the reproduction of all vertebrates.
      These hormones function through their specific receptors, so the expression
      levels of the receptors may reflect the responsibility of target organs. However,
      there was no effective method to quantify the expression levels of these
      receptors in reptilian species. In this study, we established the competitive-PCR
      assay systems for the quantification of the mRNA expression levels of three sex
      steroid hormone receptors in the leopard gecko. These assay systems were
      successfully able to detect the mRNA expression level of each receptor in various
      organs of male adult leopard geckoes. The expression levels of mRNA of these
      receptors were highly various depending on the organs assayed. This is the first
      report regarding the tissue distributions of sex steroid hormone receptor
      expressions in reptile. The effects of environmental conditions on these hormone
      receptor expressions were also examined. After the low temperature and short
      photoperiod treatment for 6 weeks, only the androgen receptor expression was
      significantly increased in the testes. The competitive-PCR assay systems
      established in this report should be applicable for various studies of the
      molecular mechanism underlying the reproductive activity of the leopard gecko.

PMID- 14662319
TI  - A novel strategy for allogeneic stem cell transplantation: perfusion method plus
      intra-bone marrow injection of stem cells.
AB  - Using long bones of cynomolgus monkeys, we have recently developed a new
      "Perfusion Method (PM)" for harvesting bone marrow cells (BMCs) while minimizing
      the contamination of BMCs with T cells from the peripheral blood. When thus
      collected BMCs, which contain not only pluripotent hemopoietic stem cells (P
      HSCs) but also mesenchymal stem cells (MSCs), are directly injected into the bone
      marrow cavity of recipients (intra-bone marrow BMT: "IBM-BMT"), the donor-derived
      hemopoietic cells quickly recover even when the radiation doses used as the
      conditioning regimen are reduced. Recipient mice, rats, and even monkeys show
      neither graft-vs-host disease (GVHD) nor graft failure. In this article, we
      discuss why this new method (PM+IBM-BMT) may become a valuable strategy for
      allogeneic stem cell (both P-HSC and MSC) transplantation.

PMID- 14662320
TI  - The potential for proteomic definition of stem cell populations.
AB  - Embryonic and adult stem cell populations have great potential value in medicine,
      and hematopoietic stem cells are already being used in transplantation.
      Definition of these populations to increase our understanding of the programs
      that control differentiation, self-renewal, and possibly plasticity would be of
      great interest. The relative quantitation of transcriptional activity in stem
      cells and other populations has defined a profile of gene expression activity in
      stem cells. Confirmation that these differences have an impact on protein levels
      within stem cells via their complete protein complement and protein interactions
      will enable further understanding of regulatory processes in these cells. The
      recent developments in proteomics and their potential application to the
      definition of the stem cell proteome are discussed, and examples are given.
      Advances in mass spectrometry, subcellular prefractionation protocols, and
      electrophoresis that make stem cell proteomics a tractable problem are discussed.
      Beyond the proteome per se, advances in post-translational modification profiling
      mean that comparative analysis of phosphorylation patterns between stem cells and
      other populations can be approached.

PMID- 14662321
TI  - Embryonic origins of mammalian hematopoiesis.
AB  - Hematopoiesis and vasculogenesis in the mammalian embryo begin in the blood
      islands of the yolk sac and continue, somewhat later, within the embryo proper. A
      subset of the first endothelial and hematopoietic cells of the yolk sac arise in
      close spatial and temporal association, apparently from a common mesodermal
      progenitor, the "hemangioblast." The mechanisms that control formation of
      hemangioblast and embryonic hematopoietic and endothelial (angioblastic)
      stem/progenitor cells are still not well understood. Formation of these cell
      types from nascent mesoderm requires signals from an adjacent outer layer of
      primitive (visceral) endoderm. Indian hedgehog (Ihh), a member of the hedgehog
      family of extracellular morphogens, is secreted by visceral endoderm and alone is
      sufficient to induce hematopoiesis and vasculogenesis in explanted embryos. While
      gene targeting studies in mice support a role for hedgehog signaling in these
      processes in vivo, they also suggest that additional molecules (perhaps, for
      example, Wnt proteins) are required for induction and patterning of hematopoietic
      and vascular mesoderm. Indian hedgehog likely functions through upregulation of
      genes encoding other signaling molecules, such as bone morphogenetic protein
      (Bmp)-4, in the target tissue. This review will focus on hematopoietic and
      vascular development in the early mouse embryo and will discuss potential
      implications of recent studies for stem cell transplantation in humans.

PMID- 14662322
TI  - SHIP, SHIP2, and PTEN activities are regulated in vivo by modulation of their
      protein levels: SHIP is up-regulated in macrophages and mast cells by
      lipopolysaccharide.
AB  - The phosphatidylinositol-3 kinase (PI3K) pathway plays a central role in
      regulating numerous biologic processes, including survival, adhesion, migration,
      metabolic activity, proliferation, differentiation, and end cell activation
      through the generation of the potent second messenger PI-3,4,5-trisphosphate (PI
      3,4,5-P(3)). To ensure that activation of this pathway is appropriately
      suppressed/terminated, the ubiquitously expressed 54-kDa tumor suppressor PTEN
      hydrolyzes PI-3,4,5-P(3) to PI-4,5-P(2), whereas the 145-kDa hematopoietic
      restricted SH2-containing inositol 5'-phosphatase SHIP (also known as SHIP1), the
      104-kDa stem cell-restricted SHIP sSHIP, and the more widely expressed 150-kDa
      SHIP2 break it down to PI-3,4-P(2). In this review, we focus on the properties of
      these phospholipid phosphatases and summarize recent data showing that the
      activities of these negative regulators often are modulated by simply altering
      their protein levels. We also highlight the critical role that SHIP plays in
      lipopolysaccharide-induced macrophage activation and in endotoxin tolerance.

PMID- 14662323
TI  - Busulfan-cyclophosphamide versus total body irradiation-cyclophosphamide as
      preparative regimen before allogeneic hematopoietic stem cell transplantation for
      acute myeloid leukemia: what have we learned?
AB  - Most of the preparative regimens before allogeneic bone marrow transplantation
      include cyclophosphamide (Cy) with either busulfan (Bu) or total body irradiation
      (TBI). The Bu-Cy regimen has shown an advantage in chronic myeloid leukemia and
      TBI-Cy remains the standard conditioning regimen in acute lymphoblastic leukemia,
      but results are more conflicting in acute myeloid leukemia (AML). We report here
      the results of the most important studies comparing these two preparative
      regimens in AML. Survival is superior in all studies for patients treated with
      TBI and reached statistical significance in one of four trials. Two of three
      trials show significantly reduced transplant mortality and leukemia relapse.
      Higher incidences of veno-occlusive disease and hemorrhagic cystitis are reported
      with Bu. However, our long-term follow-up is limited, and to date no definitive
      conclusion can be drawn regarding late side effects. New approaches aiming at
      minimizing the toxicity without impairing the efficacy, such as targeted Bu
      plasma levels and nonmyeloablative conditioning regimens, seem promising but need
      to be evaluated further in future prospective studies.

PMID- 14662324
TI  - Antigen presentation in graft-vs-host disease.

PMID- 14662325
TI  - Differential role of Stat5 isoforms in effecting hematopoietic recovery induced
      by Mpl-ligand in lethally myelosuppressed mice.
AB  - OBJECTIVE: To determine the role of the c-terminal half of c-Mpl in Mpl-L-induced
      myeloprotection and the importance of Stat5 isoforms in the survival signaling
      pathways induced by Mpl ligand. MATERIALS AND METHODS: Delta60-Mpl knockin mice,
      Stat5a(-/-)/b(-/-), Stat5a(-/-), and Stat5b(-/-) mice and wild-type (WT) controls
      were given a lethal myelosuppressive regimen: 80 mg/kg carboplatin intravenously
      followed by 7.5 or 6.5 Gy 137Cs total-body irradiation. A single dose of PEG
      rmMGDF (65 microg/kg) was intravenously injected immediately after
      myelosuppression. Mice survival and blood counts were monitored for 22 days
      posttreatment. RESULTS: Knockin Delta60-Mpl mice lacking the c-terminal half of
      the intracellular domain of c-Mpl show reduced ability of Mpl-L to prevent lethal
      myelosuppression and an impaired thrombopoietic response to exogenous c-Mpl
      ligand. The survival of Mpl-L-treated Stat5a(-/-)/b(-/-) mice exposed to the
      lethal myelosuppressive regimen was substantially compromised compared to that of
      WT mice. Reduced survival of Stat5a(-/-)/b(-/-) mice was due to more severe
      hematopoietic suppression. Deletion of Stat5a did not result in a defect in
      hematopoietic recovery. In contrast, Mpl-L-treated Stat5b-deficient mice
      demonstrated significantly delayed hematopoietic recovery compared to WT
      controls. CONCLUSIONS: Myeloprotective signaling transduced by the terminal 60
      amino acids of the intracellular domain of c-Mpl is essential for complete
      protection from lethal myelosuppression provided by Mpl-L. Our studies
      differentiate the functions of Stat5 isoforms in hematopoietic stress and reveal
      a pivotal role of Stat5b in Mpl-L-induced hematopoietic recovery in this lethal
      myelosuppression model.

PMID- 14662326
TI  - Predictable and efficient retroviral gene transfer into murine bone marrow
      repopulating cells using a defined vector dose.
AB  - OBJECTIVE: Current protocols of retroviral gene transfer into murine
      hematopoietic stem cells (HSC) result in variable gene transfer efficiency and
      involve various procedures that are not clinically applicable. We developed and
      evaluated a reliable transduction protocol that is more related to clinical
      methods. MATERIALS AND METHODS: HSC were enriched from steady-state bone marrow
      by magnetic cell sorting (lineage depletion) and cultured in defined serum-free
      medium containing an improved growth factor cocktail (Flt3-ligand, stem cell
      factor, interleukin-3, interleukin-11). Cell-free ecotropic retroviral vector
      particles, generated by transient transfection of human 293T-based packaging
      cells, were preloaded at defined titers on CH296-coated tissue culture plates,
      thus largely avoiding serum contamination. These conditions were evaluated in 17
      experiments involving 29 transduction cultures and 185 recipient mice. RESULTS:
      After two rounds of infection, the gene marking rates in cultured mononuclear
      cells and stem/progenitor cells (Lin(-)c-Kit(+)) were 15 to 85% (53.7%+/-21.7%,
      n=23) and 30 to 95% (69.8%+/-20.4%, n=17), respectively. Even after one round of
      infection, gene transfer was efficient (31.2%+/-15.1%, n=12). Using identical
      conditions, gene transfer rates were highly reproducible. Average transgene
      expression in reconstituted animals correlated well with pretransplant data.
      Using a moderate multiplicity of infection, the majority of transduced cells
      carried less than three transgene copies. In addition, coinfection was possible
      to establish two different vectors in single cells. CONCLUSION: The protocol
      described here achieves efficient retroviral transduction of murine bone marrow
      repopulating cells with a defined gene dosage, largely avoiding procedures that
      decrease stem cell output and repopulating capacity. This protocol may help to
      improve the predictive value of preclinical efficiency/toxicity studies for gene
      therapeutic interventions and basic research.

PMID- 14662327
TI  - Efficient protection from methotrexate toxicity and selection of transduced human
      hematopoietic cells following gene transfer of dihydrofolate reductase mutants.
AB  - OBJECTIVE: While retrovirally mediated gene transfer of dihydrofolate reductase
      mutants (mutDHFR) has convincingly been demonstrated to confer methotrexate (MTX)
      resistance to murine hematopoietic cells, clinical application of this technology
      will require high efficacy in human cells. Therefore, we investigated retroviral
      constructs expressing various point mutants of human DHFR for their ability to
      confer MTX resistance to human clonogenic progenitor cells (CFU-C) and to allow
      for in vitro selection of transduced CFU-C. METHODS: Primary human hematopoietic
      cells were retrovirally transduced using MMLV- and SFFV/MESV-based vectors
      expressing DHFR(Ser31), DHFR(Phe22/Ser31), or DHFR(Tyr22/Gly31). MTX resistance
      of unselected and in vitro-selected CFU-C was determined using MTX-supplemented
      methylcellulose cultures and gene transfer efficiency was assesed by single
      colony PCR analysis. RESULTS: While less than 1% mock-transduced CFU-C survived
      the presence of > or =5 x 10(-8) M MTX, MMLV- and SFFV/MESV-based vectors
      expressing DHFR(Ser31) significantly protected CFU-C from MTX at doses ranging
      from 2.5 to 30 x 10(-8) M. Vectors expressing DHFR(Phe22/Ser31) or
      DHFR(Tyr22/Gly31) were even more protective and MTX-resistant CFU-C were observed
      up to 1 x 10(-5) M MTX. Three-day suspension cultures in the presence of 10-20 x
      10(-8) M MTX resulted in significant selection of mutDHFR-transduced CFU-C. The
      percentage of CFU-C resistant to 10 x 10(-8) M MTX increased fourfold to 20-fold
      and provirus-containing CFU-C increased from 27% to 79-100%. CONCLUSION: Gene
      transfer of DHFR using suitable retroviral backbones and DHFR mutants
      significantly increases MTX resistance of human CFU-C and allows efficient in
      vitro selection of transduced cells using a short-term selection procedure.

PMID- 14662328
TI  - Enhancement of gene transfer with recombinant adeno-associated virus (rAAV)
      vectors into primary B-cell chronic lymphocytic leukemia cells by CpG
      oligodeoxynucleotides.
AB  - OBJECTIVE: Transduction of primary B-cell chronic lymphocytic leukemia (B-CLL)
      cells with recombinant adeno-associated virus (rAAV) vectors is dependent on
      preactivation of leukemic cells by CD40L. CpG-oligodeoxynucleotides (CpG-ODNs)
      are able to activate cytokine production and proliferation of B-CLL cells.
      Therefore CpG-ODNs were tested for their potential to enhance transgene
      expression in CLL cells. MATERIALS AND METHODS: Using an optimized adenovirus
      free packaging system, rAAV vectors coding for the enhanced green fluorescent
      protein (AAV/EGFP) were packaged and highly purified resulting in infectious
      titers up to 5 x 10(9)/mL. Cells obtained from patients with B-CLL were infected
      with AAV/EGFP at a multiplicity of infection of 100 while being stimulated with
      CpG-ODNs and/or CD40L-expressing HeLa/SF cells. Transgene expression was assessed
      after 48 hours by flow cytometry. RESULTS: Stimulation of B-CLL cells by CpG-ODNs
      resulted in up-regulation of costimulatory molecules and G(1)/S-phase transition
      at similar levels compared to activation by HeLa/SF cells, but use of CpG-ODNs
      alone did not result in any efficient AAV/EGFP transduction. Combined stimulation
      of B-CLL cells with HeLa/SF cells and CpG-ODNs during AAV/EGFP transduction
      significantly enhanced transgene expression compared to feeder stimulation alone
      (p=0.004). In addition, the copy number per single cell was significantly
      increased by addition of CpG-ODNs as detected by quantitative real-time PCR
      (p=0.04). Use of self-complementary AAV vectors that are not dependent on target
      cell DNA synthesis did not result in increased transgene expression compared to
      single-stranded AAV vectors (p=0.30). CONCLUSION: Stimulation by CD40L is crucial
      for efficient gene transfer into B-CLL cells by rAAV vectors, whereas
      transduction efficiency can be significantly enhanced by CpG-ODNs.

PMID- 14662329
TI  - B-cell deficiency and reduced B-cell reconstitution in hemoglobin-deficit mice.
AB  - OBJECTIVE: To study the effect of persistent hemoglobin-deficit mutation
      (hbd/hbd) on hematopoiesis and the function of hematopoietic stem cells (HSCs).
      METHODS: Young and old mice homozygous for the spontaneous hbd/hbd mutation were
      compared to young and old wild-type control mice, all on the C57BL/6 background,
      over cellular composition in blood and bone marrow (BM) using cell counting,
      complete blood counts, and flow cytometry. BM cells from hbd/hbd mutants and
      normal controls were also tested for HSC engraftment in vivo using the
      competitive repopulation assay. RESULTS: Both young and old hbd/hbd mutants
      exhibited a microcytic anemia with significantly (p<0.01) lower levels of
      hemoglobin and mean corpuscular volume. There were significant declines in CD45R+
      B cells in both blood (p<0.01) and BM (p<0.05) in old hbd/hbd mice, suggesting
      that B-cell homeostasis was compromised. Total BM cells per mouse was
      significantly increased (p<0.05) in old hbd/hbd mice. In the competitive
      repopulation assay in vivo, BM cells from old hbd/hbd donors showed slightly
      decreased contribution to T cells and myeloid cells but a significantly (p<0.01)
      decreased engraftment in B lymphocytes, indicating that B-cell hematopoiesis was
      compromised in old hbd/hbd mice. These data differ from results previously
      obtained from normal C57BL/6 mice in which BM cell engraftment ability does not
      decrease with donor age. CONCLUSION: Persistent hbd/hbd mutation causes
      hematopoiesis defects in the B cell lineage.

PMID- 14662330
TI  - Ex vivo manipulation of umbilical cord blood-derived hematopoietic
      stem/progenitor cells with recombinant human stem cell factor can up-regulate
      levels of homing-essential molecules to increase their transmigratory potential.
AB  - OBJECTIVE: The cause of delayed hematopoietic reconstitution after umbilical cord
      blood transplantation (UCBT) remains controversial. We hypothesized that
      hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the
      homing-related molecules responsible for their slow engraftment. MATERIALS AND
      METHODS: A homing-related molecule repertoire expressed on HS/PCs from fresh and
      cryopreserved UCB, mobilized peripheral blood (mPB), and bone marrow (BM) were
      compared using sensitive, four-color fluorescence-activated cell sorting
      analysis. Purified CD34+ cells were subjected to ex vivo transmigration through
      double-coated transwell filter inserts, and an in vivo homing assay was performed
      in xenotransplanted NOD/SCID mice. RESULTS: UCB-derived CD34(bright) cells
      expressed significantly lower levels of CD49e, CD49f, and CXCR-4 than their mPB
      and BM counterparts. CD34+ cells from UCB (and BM) exhibited significantly lower
      ex vivo transmigration than those from mPB, which were largely blocked by
      neutralizing antibodies to CD49e or CD49f. Recombinant human tumor necrosis
      factor-alpha treatment enhanced ex vivo transmigration of CD34+ cells from UCB
      and BM by inducing expression of the matrix metalloproteinases MMP-2/MMP-9. Short
      term treatment of UCB-derived CD34+ cells with rHu-stem cell factor (rHuSCF) up
      regulated levels of the homing-related molecules with their increased ex vivo
      transmigratory and in vivo homing potential. CONCLUSION: Our results indicate
      that disadvantageous transmigratory behavior of HS/PCs from UCB, which might
      partly explain the delayed reconstitution after UCBT, can be reversed by ex vivo
      manipulation with rHuSCF.

PMID- 14662331
TI  - Bone marrow transplant completely rescues hematolymphoid defects in STAT5A/5B
      deficient mice.
AB  - OBJECTIVE: STAT5A/5B-deficient mice are recognized to manifest defects in
      multiple cell types and tissues. In particular, the hematopoietic defects in
      these mice are widespread, affecting multiple lineages and multiple stages of
      development. Previous studies indicate that deficiencies intrinsic to
      hematopoietic cells contribute substantially to the observed defects. However, in
      light of the broad physiologic effects of STAT5 in the context of the organism
      outside the blood system, we wished to investigate the possibility of STAT5
      dependent environmental influence of nonhematopoietic origin on hematopoietic
      development in these mice. MATERIALS AND METHODS: We transplanted wild-type bone
      marrow into STAT5A/5B-deficient mice to determine the effects of loss of STAT5 in
      nonhematopoietic tissue on hematopoietic development. RESULTS: We observed that
      transplantation of wild-type marrow completely corrects hematopoietic defects in
      STAT5A/5B-deficient recipient mice, including peripheral blood counts, bone
      marrow cellularity, and reductions in specific progenitor subsets. CONCLUSION:
      These results indicate that the important role of STAT5 in hematolymphoid
      development are mediated directly through effects on hematopoietic cells and not
      indirectly.

PMID- 14662332
TI  - Transgenic bcl-2 is not sufficient to rescue all hematolymphoid defects in
      STAT5A/5B-deficient mice.
AB  - OBJECTIVE: Cytokines bind high-affinity receptors expressed on hematopoietic
      cells to initiate signaling cascades that regulate differentiation,
      proliferation, and survival. Previous studies have established a role for STAT5
      in transducing survival signals for hematopoietic progenitor cells in response to
      cytokines. MATERIALS AND METHODS: To determine if constitutive expression of a
      member of the bcl-2 family of anti-apoptotic proteins could compensate for the
      loss of STAT5, we utilized combinatorial genetics to generate STAT5A/5B-deficient
      mice expressing a bcl-2 transgene. RESULTS: Although bcl-2 expression restored
      peripheral blood counts to normal in STAT5A/5B(-/-) mice, we noted a striking
      failure of this transgene to correct defects in hematopoietic stem and progenitor
      cells. CONCLUSION: These data imply important effects of STAT5 in modulating
      hematopoietic cells in addition to promoting survival per se.

PMID- 14662333
TI  - The fps/fes proto-oncogene regulates hematopoietic lineage output.
AB  - OBJECTIVE: The fps/fes proto-oncogene is abundantly expressed in myeloid cells,
      and the Fps/Fes cytoplasmic protein-tyrosine kinase is implicated in signaling
      downstream from hematopoietic cytokines, including interleukin-3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin
      (EPO). Studies using leukemic cell lines have previously suggested that Fps/Fes
      contributes to granulomonocytic differentiation, and that it might play a more
      selective role in promoting survival and differentiation along the monocytic
      pathway. In this study we have used a genetic approach to explore the role of
      Fps/Fes in hematopoiesis. METHODS: We used transgenic mice that tissue
      specifically express a mutant human fps/fes transgene (fps(MF)) that was
      engineered to encode Fps/Fes kinase that is activated through N-terminal
      myristoylation (MFps). Hematopoietic function was assessed using lineage
      analysis, hematopoietic progenitor cell colony-forming assays, and biochemical
      approaches. RESULTS: fps(MF) transgenic mice displayed a skewed hematopoietic
      output reflected by increased numbers of circulating granulocytic and monocytic
      cells and a corresponding decrease in lymphoid cells. Bone marrow colony assays
      of progenitor cells revealed a significant increase in the number of both
      granulomonocytic and multi-lineage progenitors. A molecular analysis of signaling
      in mature monocytic cells showed that MFps promoted GM-CSF-induced STAT3, STAT5,
      and ERK1/2 activation. CONCLUSIONS: These observations support a role for Fps/Fes
      in signaling pathways that contribute to lineage determination at the level of
      multi-lineage hematopoietic progenitors as well as the more committed
      granulomonocytic progenitors.

PMID- 14662334
TI  - Identification and activation of Src family kinases in primary megakaryocytes.
AB  - OBJECTIVES: We have recently shown that the Src family of tyrosine kinases (SFKs)
      are activated by TPO stimulation in both primary megakaryocytic progenitors and a
      hematopoietic cells line (BaF3) expressing the TPO receptor (Mpl). In this study,
      we examine which of the eight Src family members are expressed in primary
      megakaryocytes (MKs) and determine which of these become activated in response to
      TPO. MATERIALS AND METHODS: High-density oligonucleotide microarrays were used to
      compare the gene expression profiles of Src kinases from undifferentiated
      hematopoietic progenitors (CD34+/CD38(lo)) and after in vitro megakaryocytic
      differentiation. Western blot analysis of lysates from purified, mature murine
      MKs identified which of SFKs are present. Finally, in vitro kinase assays
      determined which of the SFKs in primary MKs are activated by TPO stimulation.
      RESULTS: Array profiles demonstrate that Fyn, Lyn, Fgr, Hck, Src, and Yes are all
      expressed in cultured human MKs (Fyn, Lyn>Src, Yes, Fgr, Hck). Similarly, Western
      blots of murine MKs identified the same six SFKs (Fyn, Fgr, Hck, Lyn, Src, and
      Yes). Of these, only Fyn and Lyn demonstrate increased kinase activity after TPO
      stimulation. Interestingly, gene expression analysis indicates that, among the
      SFKs, Fyn expression is uniquely upregulated during MK development. CONCLUSION:
      These results provide the first direct evidence that two Src kinases are
      activated in primary MKs, Fyn and Lyn. The fact that only Fyn expression is
      significantly upregulated during MK differentiation suggests variable gene
      regulation. Specificity of the TPO signaling cascade is demonstrated by the
      selective activation of Fyn and Lyn.

PMID- 14662335
TI  - CD34+CDw90(Thy-1)+ subset colocated with mesenchymal progenitors in human normal
      bone marrow hematon units is enriched in colony-forming unit megakaryocytes and
      long-term culture-initiating cells.
AB  - OBJECTIVE: The progress made in the supportive care of allografts and the
      identification of mesenchymal stem cells in adult human bone marrow (BM) has
      prompted renewed interest in the use of BM as a form of cell therapy. With the
      aim of optimizing the collection of BM cells, we evaluated the hematopoietic and
      mesenchymal immature cell contents of BM hematon units (HUs), which usually are
      eliminated during graft processing. MATERIALS AND METHODS: Hematopoietic CD34+
      progenitors from HU and buffy coat (BC) compartments were characterized in short
      term culture. The sorted CD34+CDw90(Thy-1)+ primitive subset was assessed in
      colony-forming cell (CFC) and long-term culture-initiating cell (LTC-IC) assays,
      then further characterized by the expression of additional antigens. In parallel,
      we evaluated the colony-forming unit fibroblast (CFU-F) number and phenotyped the
      fresh adherent (D1-3) cells. RESULTS: The plating efficiencies of CD34+ cells
      derived from HU and BC were identical. However, the HU CD34+CDw90(Thy-1)+ subset
      was enriched in colony-forming unit megakaryocyte (2.3x), LTC-IC (4.6x), and
      cells coexpressing CD105 (5x). We found a higher frequency of CFU-F (4.7x),
      considered to be the mesenchymal stem cell-containing population, correlated with
      an enrichment in fresh adherent (CD45/GPA)-CD14- cells. CONCLUSIONS: We show for
      the first time that functional properties of the CD34+CDw90+ subset are related
      to its in vivo location in HU, which may represent the BM mesenchymal reserve
      compartment. The location in HU of 35.6%, 59.1%, and 58.7% of CD34+ cells,
      CD34+CDw90+ LTC-IC, and CFU-F, respectively, justifies the development of a
      procedure to collect them in order to reduce the therapeutic BM volume.

PMID- 14662336
TI  - Membrane-bound stem cell factor is a key regulator in the initial lodgment of
      stem cells within the endosteal marrow region.
AB  - OBJECTIVE: The transmembrane isoform of stem cell factor (tm-SCF) has been
      implicated in the adhesion of hemopoietic stem cells to the extracellular matrix
      within the bone marrow microenvironment in vitro. In addition, in vivo SCF has
      been shown to play a role in cell mobilization and migration. The aim of this
      study was to determine if SCF is an integral component of the hemopoietic "niche"
      of the bone marrow in situ. MATERIALS AND METHODS: To analyze the role of tm-SCF
      in cell lodgment, purified populations of primitive progenitors and hemopoietic
      stem cells (HSC) were transplanted into a hemopoietic microenvironment devoid of
      tm-SCF, and the spatial distribution of engrafted cells was analyzed. In
      addition, populations of HSC were isolated using non-neutralizing and
      neutralizing antibodies to the SCF receptor c-kit, and their spatial distribution
      was analyzed post-transplant. RESULTS: The data demonstrated a significant
      impairment in the lodgment of transplanted cells within the endosteal marrow
      region in mice lacking tm-SCF, with a reduction of almost 30% by 15 hours post
      transplant. The role of tm-SCF was confirmed by analyzing the spatial
      distribution of HSC isolated using a neutralizing antibody to c-kit. CONCLUSION:
      The data demonstrate that although tm-SCF does not appear to play a role in the
      homing of transplanted cells to the bone marrow, it is critical in the lodgment
      and detainment of HSC within their hemopoietic "niche."

PMID- 14662337
TI  - Characterization of adhesion and viability of early seeding hematopoietic cells
      in the host bone marrow in vivo and in situ.
AB  - OBJECTIVE: Homing and seeding are essential early events of engraftment that
      depend on the interaction of hematopoietic cells with the host bone marrow (BM)
      stroma. We used optical techniques to characterize the adhesion patterns and
      viability of bone marrow cells (BMC) at the level of recipient BM
      microenvironment. MATERIALS AND METHODS: Donor cells labeled with PKH dyes were
      tracked in vivo through an optical window placed over the femoral epiphysis of
      nonconditioned recipients. Adhesion to BM stroma was assessed with laser
      tweezers, and viability was assayed by fluorescence resonance energy transfer of
      the pair PKH67-propidium iodide (PI) in freshly excised femurs. RESULTS: Three
      hours after intravenous injection, an estimated 30% of the labeled cells in the
      femur were immobile. The percent of adherent cells increased to 74+/-3% and 97+/
      2% on days +1 and +3, respectively, (p<0.001), and similar fractions of cells
      were viable at these times (p<0.001). The observation that all adherent cells
      were viable suggested a correlation between these parameters. The day +3 BM
      seeded cells rescued secondary myeloablated allogeneic hosts. Seeding in the host
      BM was accompanied by (4.5-fold) enrichment of cells expressing SCA-1 and was 22
      fold higher for lineage-negative Lin(-) cells compared to lineage-positive cells
      (p<0.001). Pretreatment of Lin(-) cells with anti-VLA-4 antibodies caused a 2.4
      fold decrease in homing and a 4.6-fold decrease in seeding (p<0.001).
      CONCLUSIONS: The data indicate that adhesion is rate-limiting determinant of
      homing and early seeding, and a crucial event that preserves the viability of
      cells toward successful engraftment. The role of VLA-4 is more important for
      primary seeding than it is for homing to the BM.

PMID- 14662338
TI  - Angiotensin-converting enzyme (CD143) is abundantly expressed by dendritic cells
      and discriminates human monocyte-derived dendritic cells from acute myeloid
      leukemia-derived dendritic cells.
AB  - OBJECTIVES: The pattern of angiotensin-converting enzyme (ACE) expression in
      dendritic cells (DC) and macrophages derived from normal monocytes vs that in DC
      derived from acute myeloid leukemia blasts was investigated. MATERIALS AND
      METHODS: ACE expression was quantified by flow cytometry using a set of
      monoclonal antibodies (mAbs) directed against five different epitopes on the ACE
      molecule and by enzyme activity measurement. RESULTS: The binding pattern of a
      set of anti-ACE mAbs to the surface of blood cells and their progeny, as revealed
      by FACS, showed lineage and epitope specificity. Differentiation of monocytes to
      macrophages and DC was accompanied by a dramatic increase in ACE expression. ACE
      activity was 50-fold higher in macrophages and 150-fold higher in DC than in
      monocytes. ACE level normalized per cell revealed that DC expressed 1300-fold
      more ACE than did monocytes. In contrast, DC derived from acute myeloid leukemia
      blasts did not show an elevated level of ACE, although they acquired DC markers
      CD80, CD40, and CD86 upon cytokine or calcium ionophore treatment. CONCLUSIONS:
      ACE expression becomes the first marker to functionally distinguish DC generated
      from monocytes and leukemic blast cells. Given that ACE plays an important role
      in the hydrolysis of many peptides, as well as in the presentation of some
      antigens to immune cells, these data suggest that elevated ACE expression on the
      surface of DC is not just a reflection of the general activation of monocytes
      during differentiation; rather, it may be physiologically important for the
      functioning of these cells.

PMID- 14662339
TI  - Hematopoietic cell survival signals are elicited through non-tyrosine-containing
      sequences in the membrane-proximal region of the erythropoietin receptor (EPOR)
      by a Stat5-dependent pathway.
AB  - OBJECTIVE: Erythropoietin is essential for red blood cell development in vivo and
      is also an important therapeutic agent to treat anemia resulting from kidney
      failure or bone marrow suppression. The erythropoietin receptor (EPOR) elicits
      both positive and negative regulatory signaling pathways, primarily through
      phosphorylated tyrosine residues in the cytoplasmic domain of the activated
      receptor complex. Surprisingly, however, EPOR tyrosine residues are dispensable
      for in vivo erythropoiesis under nonstress conditions. One of the key signaling
      molecules elicited by the EPOR is the Stat5 transcription factor. Stat5
      activation has been mapped to tyrosines 343 and 401 in the EPOR cytoplasmic
      region, although non-tyrosine-containing sequences in the EPOR cytoplasmic region
      can also stimulate Stat5. To test the functional role of non-tyrosine-containing
      sequences in the EPOR, we analyzed a series of mutant EPOR isoforms in cell
      survival and proliferation assays. METHODS: The IL-3-dependent 32D cell line was
      stably transfected with cDNAs encoding the wild-type EPOR or mutant EPORs
      containing or lacking intracellular tyrosines, in the absence or presence of a
      dominant inhibitory Stat5 isoform. EPO-dependent cell signaling, survival, and
      proliferation were evaluated. RESULTS: EPOR isoforms lacking intracellular
      tyrosine residues elicit an important survival signal in 32D cells. Stat5
      function is critical for EPO-dependent cell survival mediated by these non
      tyrosine-containing receptor sequences. Interestingly, EPO-dependent survival
      does not require the presence of fetal calf serum (FCS) in the culture medium,
      yet FCS is important for 32D cell proliferation in response to EPO. CONCLUSION:
      Our results elucidate a previously unrecognized survival pathway elicited by the
      EPOR. They demonstrate that this pathway requires Stat5 and is serum independent.
      These findings contribute significantly to our understanding of the complexity by
      which the EPOR functions in hematopoietic cells.

PMID- 14662340
TI  - Limitin, an interferon-like cytokine, transduces inhibitory signals on B-cell
      growth through activation of Tyk2, but not Stat1, followed by induction and
      nuclear translocation of Daxx.
AB  - OBJECTIVE: Limitin, an interferon-like cytokine, suppresses B lymphopoiesis
      through ligation of the interferon-alpha/beta (IFN-alpha/beta) receptor. The aim
      of this study was to examine the intracellular signal transduction pathways
      activated by limitin. MATERIALS AND METHODS: The effects of limitin on cell
      growth, the activation of Jak kinase and Stat proteins, and the induction of
      interferon regulatory factor-1 (IRF-1) and Daxx were examined using the mouse pre
      B-cell line 18.81, wild-type, and Tyk2-deficient mouse bone marrow cells. In
      addition, the change of localization of the Daxx protein after limitin treatment
      in wild-type and Tyk2-deficient mice was examined. RESULTS: Limitin
      phosphorylates Tyk2, Jak1, Stat1, and Stat2 and rapidly induces IRF-1 mRNA
      production. Phosphorylation of Stat1 by limitin is partially dependent on Tyk2.
      Suppression of B-cell growth by limitin, however, is severely impaired in the
      absence of Tyk2, whereas it is unaffected by the absence of Stat1. Limitin also
      induces the expression and nuclear translocation of Daxx, which is essential for
      IFN-alpha-induced inhibition of B-lymphocyte development. The absence of Tyk2
      abrogates this induction of Daxx expression and nuclear translocation.
      CONCLUSIONS: Limitin suppresses B-cell growth through activation of Tyk2,
      resulting in the up-regulation and nuclear translocation of Daxx. This limitin
      mediated signaling pathway does not require Stat1.

PMID- 14662341
TI  - In vivo and in vitro differentiation of myocytes from human bone marrow-derived
      multipotent progenitor cells.
AB  - OBJECTIVE: Recent studies have shown that bone marrow (BM) contains cells capable
      of differentiating into myocytes in vivo. However, addition of demethylation
      drugs has been necessary to induce myocyte differentiation from BM cells in
      vitro, and precise mechanisms of BM cells' conversion to myocytes and the origin
      of those cells have not been established. We investigated the expression of
      myogenic markers during differentiation and maturation of myocytes from BM
      derived multipotent adult progenitor cells (MAPC) under physiological culture
      condition. MATERIALS AND METHODS: Frozen BM samples from 21 healthy donors were
      used as a source of MAPC. To induce myocyte differentiation MAPC was cultured in
      the presence of 5% FCS, VEGF, bFGF, and IGF-1, and the expressions of myocyte
      markers were examined at various time points. We also investigated engraftment
      and differentiation of MAPC-derived myocytes in vivo. RESULTS: Frozen BM-derived
      MAPC, cultured under the physiological myogenic condition, demonstrated spatial
      expression patterns of several myocyte markers similar to that of authentic
      myocyte differentiation. When injected into murine muscles, MAPC treated with the
      myogenic condition engrafted and differentiated into myocyte marker-positive
      cells and myotubes in vivo. CONCLUSION: For the first time, we were able to
      induce myocyte formation from BM cells under the physiological condition in vitro
      and demonstrated that treating cells with this condition prior to intramuscular
      injection increased efficiency of engraftment and differentiation in vivo.

PMID- 14662342
TI  - Expression change of Flk-2/Flt-3 on murine hematopoietic stem cells in an
      activating state.
AB  - OBJECTIVE: The receptor tyrosine kinase Flk-2/Flt-3 (Flt-3) represents an
      important molecule involved in early hematopoiesis. Murine hematopoietic stem
      cells (HSCs) have been shown to be negative for the expression of Flt-3. We now
      present clear evidence for the expression change of Flt-3(-) HSCs in an
      activating state, and the reversibility of Flt-3 expression by HSCs in vivo.
      MATERIALS AND METHODS: Bone marrow cells isolated from Ly5.1 mice were sorted on
      the basis of Flt-3 expression and transplanted into lethally irradiated Ly5.2
      recipients. After 24 weeks, peripheral blood was analyzed for donor contribution
      by flow cytometry. RESULTS: Although long-term engraftment was predominantly
      detected in Flt-3(-) populations as previously described, a 6-day cultivation of
      Lin(-/low)c-kit(+)Sca-1(+) Flt-3(-) bone marrow cells with stem cell factor and
      interleukin-11 resulted in the generation of Flt-3(+) HSCs with long-term
      engraftment capabilities. However, the Flt-3 ligand had no significant effect on
      self-renewal of the Flt-3(+) HSCs. Next, to examine reversible expression of this
      receptor molecule, Flt-3(+) cells converted in vitro from Ly5.1 Lin(-/low)c
      kit(+)Sca-1(+) Flt-3(-) bone marrow cells were isolated and transplanted into
      Ly5.2 primary recipients. After 24 weeks, Ly5.1 Lin(-/low) bone marrow cells were
      again separated into Flt-3(-) and Flt-3(+) cells and retransplanted into Ly5.2
      secondary recipients. The majority of donor HSCs with long-term engraftment
      capabilities were detected in the Flt-3(-) populations, indicating the reversion
      of Flt-3(+) to Flt-3(-) HSCs. CONCLUSIONS: These observations suggest that Flt-3
      is a useful cell-surface marker of HSC activation and that this phenotypic change
      is reversible.

PMID- 14662343
TI  - Different in vivo repopulating activities of purified hematopoietic stem cells
      before and after being stimulated to divide in vitro with the same kinetics.
AB  - OBJECTIVE: The Hoechst 33342-effluxing side population (SP) of adult mouse bone
      marrow (BM) contains most of the hematopoietic stem cells (HSCs). Here we
      measured the HSC content of specific subsets of SP cells and then used a highly
      HSC-enriched fraction to investigate the effect of different growth factors on
      the initial rate of HSC proliferation in vitro and the accompanying maintenance
      (or loss) of HSCs in the first-division progeny. MATERIALS AND METHODS: Staining
      with Rhodamine-123 (Rho) was used to subfractionate lineage marker-negative (lin
      ) SP cells. Cells were assayed for HSCs by examining their ability to generate
      sustained (>4 months) multi-lineage lympho-myeloid clones in irradiated hosts.
      Cultures of single lin- Rho- SP cells were used to monitor growth factor effects
      on HSC proliferation and function. RESULTS: More than 40% of mice injected with
      single lin- Rho- SP cells showed long-term lympho-myeloid reconstitution. Some
      clones peaked within 8 weeks but others developed more slowly apparently
      unrelated to the pattern of lineage representation. 3/3 clones tested repopulated
      secondary mice. Either Steel factor+interleukin-11 (+/- flt3-ligand) or Steel
      factor+thrombopoietin stimulated at least 75% of single lin- Rho- SP cells to
      divide in vitro with the same synchronous kinetics. However, in the first
      cocktail, the frequency of HSCs among the first-division doublets was preserved
      but in the latter it was greatly diminished. CONCLUSION: Exogenous growth factors
      can differentially affect the ability of HSCs to execute a self-renewal division
      within a single cell cycle even when the kinetics of proliferation are the same.

PMID- 14662344
TI  - Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic
      function via apoptosis-dependent and -independent mechanisms.
AB  - OBJECTIVE: Ionizing radiation (IR) and busulfan (BU) are commonly used as
      preconditioning regimens for bone marrow transplantation (BMT). We examined
      whether induction of apoptosis in murine bone marrow (BM) hematopoietic cells
      contributes to IR- and BU-induced suppression of their hematopoietic function.
      METHODS: The hematopoietic functions of hematopoietic stem cells (HSCs) and
      progenitors were analyzed by the cobblestone area-forming cell (CAFC) assay.
      Apoptosis was determined by measuring 3,3'-dihexyloxacarbocyanine iodide (DiCO6)
      uptake, annexin V staining, and/or sub-G(0/1) cells. Four cell types were
      studied: murine BM mononuclear cells (BM-MNCs), linage-negative hematopoietic
      cells (Lin-) cells), Lin- Scal+ c-kit+ cells, and Lin- Scal- c-kit+ cells by flow
      cytometry. RESULTS: Exposure of BM-MNCs to IR (4 Gy) or incubation of the cells
      with BU (30 microM) resulted in a significant reduction in CAFC frequency
      (p<0.001). The survival fractions of various day-types of CAFC for the irradiated
      cells were less than 10%, while that for BU-treated cells was 71.3% on day 7 and
      progressively declined to 5.3% on day 35. Interestingly, IR significantly induced
      apoptosis in BM-MNCs, Lin- cells, HSCs, and progenitors, whereas BU failed to
      increase apoptosis in these cells. In addition, preincubation of BM-MNCs with z
      Val-Ala-Asp (OCH3)-fluoromethylketone, methyl ester (z-VAD) attenuated IR-induced
      reduction in CAFC but not that induced by BU. CONCLUSION: IR and BU
      differentially suppress the hematopoietic function of HSCs and progenitors by
      fundamentally different mechanisms. IR inhibits the function primarily by the
      induction of HSC and progenitor apoptosis. In contrast, BU suppresses HSC and
      progenitor function via an apoptosis-independent mechanism.

PMID- 14662345
TI  - Correction of a large animal model of type I Glanzmann's thrombasthenia by
      nonmyeloablative bone marrow transplantation.
AB  - OBJECTIVE: The purpose of this study was to determine if nonmyeloablative bone
      marrow transplantation would induce stable hematopoietic chimerism that would
      correct the bleeding diathesis associated with type I Glanzmann's thrombasthenia
      (GT). METHODS: Three young dogs (less than 12 weeks of age) with GT were
      transplanted with DLA-matched bone marrow from littermates. Recipients received a
      sublethal dose (200 cGy) of total-body irradiation (TBI) prior to infusion with
      bone marrow (1-4 x 10(8) cells/kg). Recipient dogs were immunosuppressed with
      cyclosporine (15 mg/kg) and mycophenolate mofetil (10 mg/kg). Chimerism was
      determined by quantitation of donor microsatellite repeat polymorphisms in
      peripheral blood DNA and by flow cytometry to detect the presence of
      glycoproteins IIb and IIIa on platelets. Platelet function was assessed by a clot
      retraction test. RESULTS: One dog died one week posttransplant due to hemorrhage.
      Another dog died four weeks posttransplant from an unrecognized congenital heart
      defect and complications due to canine distemper virus infection. At the time of
      death, microsatellite analysis indicated 35 to 50% chimerism. Flow cytometry
      showed 20% of circulating platelets positive for glycoproteins IIb and IIIa. The
      third dog is alive and doing well approximately two years posttransplant.
      Hematopoietic chimerism has been sustained at 35 to 60% with approximately 30% of
      the platelets positive for glycoproteins IIb and IIIa. Platelet function is
      normal based on clot retraction. The animal does not have clinical signs of
      bleeding. CONCLUSIONS: These observations suggest that GT and perhaps other
      severe inherited platelet disorders can be corrected using nonmyeloablative bone
      marrow transplantation to establish partial chimerism with normal platelets in
      the platelet compartment.

PMID- 14662346
TI  - Growth and development. Microbial development--regulation in space and time.

PMID- 14662347
TI  - Timekeeping in bacteria: the cyanobacterial circadian clock.
AB  - The prokaryotes known as cyanobacteria possess an endogenous 24h biological
      (circadian) clock that provides temporal coordination for physiological
      processes. Although the cyanobacterial clock has the same fundamental properties
      as circadian clocks in eukaryotes, its components are non-homologous to those of
      animals, plants or fungi. Moreover, its mechanism is likely to be very different
      from that depicted in eukaryotic clock models. The picture that is emerging for
      the timing mechanism in cyanobacteria is of a multiprotein, multimeric, molecular
      machine composed of proteins whose domains exhibit twists on common themes.
      Signal transduction into and out of the clock core appears to occur via histidine
      protein kinase-based phosphorylation relays.

PMID- 14662348
TI  - Cell cycle timing and developmental checkpoints in Caulobacter crescentus.
AB  - Development in Caulobacter reflects a level of complexity once thought only to
      exist in eukaryotic cells. The cell cycle and development are not isolated from
      each other, but are interdependent processes. Checkpoints are in place to ensure
      that both cell cycle and developmental processes are completed accurately before
      the next stage is initiated. The timing of these processes is regulated by signal
      transduction networks that integrate signals from DNA replication, cell division
      and development. These signal transduction networks achieve precise timing of the
      cell cycle and development by regulating temporal gene expression, and protein
      activity by dynamic spatial localization within the cell and timed proteolysis.

PMID- 14662349
TI  - Spore germination.
AB  - The germination of dormant spores of Bacillus species is the first crucial step
      in the return of spores to vegetative growth, and is induced by nutrients and a
      variety of non-nutrient agents. Nutrient germinants bind to receptors in the
      spore's inner membrane and this interaction triggers the release of the spore
      core's huge depot of dipicolinic acid and cations, and replacement of these
      components by water. These latter events trigger the hydrolysis of the spore's
      peptidoglycan cortex by either of two redundant enzymes in B. subtilis, and
      completion of cortex hydrolysis and subsequent germ cell wall expansion allows
      full spore core hydration and resumption of spore metabolism and macromolecular
      synthesis.

PMID- 14662350
TI  - Heterocyst development in Anabaena.
AB  - Many filamentous nitrogen-fixing cyanobacteria protect nitrogenase from oxygen in
      differentiated cells called heterocysts. Heterocyst development is controlled by
      the availability of nitrogen compounds in the environment and by intrinsic
      factors that regulate the frequency and pattern of heterocysts along vegetative
      cell filaments. Recent progress in understanding heterocyst development in these
      simple multicellular organisms includes demonstrating the role of 2-oxoglutarate
      in regulating the activity of the transcription factor NtcA, the identification
      of additional genes in the regulatory network, such as hetF, and the further
      characterization of previously identified genes and proteins, including
      DevR/HepK, hetR, hetN, patS and patB.

PMID- 14662351
TI  - Growth polarity and cell division in Streptomyces.
AB  - Streptomycetes are mycelial bacteria that resemble filamentous fungi in their
      apical growth, branching, and morphogenetic development. One inroad into the
      largely unknown mechanisms underlying this prokaryotic growth polarity is
      provided by Streptomyces DivIVA, a protein localized at hyphal tips and involved
      in tip extension. Another aspect is a proposed migration of nucleoids. During
      sporulation, the modes of growth and cell division are reorganised. This involves
      dynamic assembly of FtsZ into a multitude of cytokinetic rings. Controlled by
      developmental regulators and intriguingly coordinated with chromosome
      segregation, this leads to spores with a single chromosome each. Genome sequences
      have shed new light on these aspects and reinforced the role of Streptomyces in
      bacterial cell biology.

PMID- 14662352
TI  - Multicellular development and gliding motility in Myxococcus xanthus.
AB  - A great deal of progress has been made in the studies of fruiting body
      development and social gliding in Myxocococcus xanthus in the past few years.
      This includes identification of the bone fide C-signal and a receptor for type IV
      pili, and development of a model for the mechanism of adventurous gliding
      motility. It is anticipated that the next few years will see even more progress
      as the complete genome sequence is available and genomic and proteomic tools are
      applied to the study of M. xanthus social behaviors.

PMID- 14662353
TI  - Bacterial biofilms: prokaryotic adventures in multicellularity.
AB  - The development of bacterial biofilms includes both the initial social behavior
      of undifferentiated cells, as well as cell death and differentiation in the
      mature biofilm, and displays several striking similarities with higher organisms.
      Recent advances in the field provide new insight into differentiation and cell
      death events in bacterial biofilm development and propose that biofilms have an
      unexpected level of multicellularity.

PMID- 14662355
TI  - Role of penicillin-binding proteins in bacterial cell morphogenesis.
AB  - The penicillin-binding proteins (PBPs) polymerize and modify peptidoglycan, the
      stress-bearing component of the bacterial cell wall. As part of this process, the
      PBPs help to create the morphology of the peptidoglycan exoskeleton together with
      cytoskeleton proteins that regulate septum formation and cell shape. Genetic and
      microscopic studies reveal clear morphological responsibilities for class A and
      class B PBPs and suggest that the mechanism of shape determination involves
      differential protein localization and interactions with specific cell components.
      In addition, the low molecular weight PBPs, by varying the substrates on which
      other PBPs act, alter peptidoglycan synthesis or turnover, with profound effects
      on morphology.

PMID- 14662354
TI  - Chromosome segregation in Eubacteria.
AB  - It is now clear that bacterial chromosomes rapidly separate in a manner
      independent of cell elongation, suggesting the existence of a mitotic apparatus
      in bacteria. Recent studies of bacterial cells reveal filamentous structures
      similar to the eukaryotic cytoskeleton, proteins that mediate polar chromosome
      anchoring during Bacillus subtilis sporulation, and SMC interacting proteins that
      are involved in chromosome condensation. A picture is thereby developing of how
      bacterial chromosomes are organized within the cell, how they are separated
      following duplication, and how these processes are coordinated with the cell
      cycle.

PMID- 14662356
TI  - Coordination of cell cycle and cytokinesis in Trypanosoma brucei.
AB  - In common with all eukaryotic cells, trypanosomes must coordinate a complex
      series of morphogenetic events both temporally and spatially during the cell
      cycle. The structural and molecular cues that synchronise these events in
      trypanosomes have started to be elucidated, and intriguingly although
      similarities to cell cycle events in other eukaryotes can be identified,
      trypanosomes have also evolved novel solutions to the common challenges faced by
      dividing eukaryotic cells. Although cellular morphology is clearly pivotal for
      successful progression through the trypanosome cell cycle, most cytological
      studies to date have focused exclusively on procyclic form trypanosomes. These
      studies provide an excellent framework for understanding cell cycle events in
      trypanosomes, however recent data indicates that profound differences might exist
      between different life cycle stages in relation to the regulation of cell cycle
      and cytokinesis.

PMID- 14662357
TI  - Differentiation of germinal and somatic cells in Volvox carteri.
AB  - Volvox carteri is a spherical alga with a complete division of labor between
      around 2000 biflagellate somatic cells and 16 asexual reproductive cells
      (gonidia). It provides an attractive system for studying how a molecular genetic
      program for cell-autonomous differentiation is encoded within the genome. Three
      types of genes have been identified as key players in germ-soma differentiation:
      a set of gls genes that act in the embryo to shift cell-division planes,
      resulting in asymmetric divisions that set apart the large-small sister-cell
      pairs; a set of lag genes that act in the large gonidial initials to prevent
      somatic differentiation; and the regA gene, which acts in the small somatic
      initials to prevent reproductive development. Somatic-cell-specific expression of
      regA is controlled by intronic enhancer and silencer elements.

PMID- 14662359
TI  - Cell polarity and Dictyostelium development.
AB  - Cell polarity is essential for unicellular and multicellular stages of
      Dictyostelium development. Chemotaxis during early development requires each cell
      to rapidly reorganize its cytoskeleton to point towards a source of cAMP. This
      involves a balance between local induction of F-actin polymerization and
      suppression of pseudopods that point in other directions. Both the lipid
      phosphatidylinositol (3,4,5) trisphosphate and the soluble signal cGMP have been
      implicated in these processes, in addition to conserved and novel proteins.
      During later development cells adopt newly discovered, alternative modes of
      movement and interact through adhesion molecules. Finally, cells polarize
      secretion to particular regions of their surface.

PMID- 14662358
TI  - RNA asymmetric distribution and daughter/mother differentiation in yeast.
AB  - Active transport and localized translation of the ASH1 mRNA at the bud tip of the
      budding yeast Saccharomyces cerevisiae is an essential process that is required
      for the regulation of the mating type switching. ASH1 mRNA localization has been
      extensively studied over the past few years and the core components of the
      translocation machinery have been identified. It is composed of four localization
      elements (zipcodes), within the ASH1 mRNA, and at least three proteins,
      She1p/Myo4p, She2p and She3p. Whereas the movement of the RNA can be attributed
      to direct interaction with myosin, the regulation of the RNA expression is less
      well understood. Recent insights have revealed a role for translation that might
      have a key function in the regulation of Ash1 protein sorting.

PMID- 14662360
TI  - Cytoskeleton and motor proteins in filamentous fungi.
AB  - In filamentous fungi, the actin cytoskeleton is required for polarity
      establishment and maintenance at hyphal tips and for formation of a contractile
      ring at sites of septation. Recently, formins have been identified as Arp (actin
      related protein) 2/3-independent nucleators of actin polymerization, and
      filamentous fungi contain a single formin that localizes to both sites. Work on
      cytoplasmic dynein and members of the kinesin and myosin families of motors has
      continued to reveal new information regarding the function and regulation of
      motors as well as demonstrate the importance of microtubules in the long-distance
      transport of vesicles/organelles in the filamentous fungi.

PMID- 14662361
TI  - Long-lost relatives reappear: identification of new members of the tubulin
      superfamily.
AB  - The identification and analysis of new members of the tubulin superfamily has
      advanced the belief that these tubulins play important roles in the duplication
      and assembly of centrioles and basal bodies. This idea is supported by their
      distribution in organisms with centrioles containing triplet microtubules and by
      recent functional analysis of the new tubulins. delta- and epsilon-tubulin are
      found in most organisms that assemble triplet microtubules. delta-tubulin is
      needed for maintaining triplet microtubules in Chlamydomonas and Paramecium.
      epsilon-tubulin is needed for centriole and basal body duplication and is an
      essential gene in Chlamydomonas. The distribution of eta-tubulin is more limited
      and has been found in only four organisms to date. Phylogenetic analysis suggests
      that it is most closely related to delta-tubulin, which suggests that delta- and
      eta-tubulin could have overlapping functions.

PMID- 14662362
TI  - Non-Mendelian determinants of morphology in fungi.
AB  - Morphological plasticity is a hallmark of eumycetes. In addition to genes and
      environment, epigenetic factors control cell, colony and thallus forms in many
      species, by creating reversible switches. Current knowledge indicates that the
      different shapes are due to structural or regulatory heritable states of
      cytoplasmic components. Cellular physiology differs in the various forms,
      permitting adaptation to fluctuation in the environment. These switches are part
      of the adaptation repertoire that fungi exhibit to colonize most niches.

PMID- 14662364
TI  - Frontal cortical control of smooth-pursuit.
AB  - To maintain optimal clarity of objects moving slowly in three dimensional space,
      frontal eyed-primates use both smooth-pursuit and vergence (depth) eye movements
      to track precisely those objects and maintain their images on the foveae of left
      and right eyes. The caudal parts of the frontal eye fields contain neurons that
      discharge during smooth-pursuit. Recent results have provided a new understanding
      of the roles of the frontal eye field pursuit area and suggest that it may
      control the gain of pursuit eye movements, code predictive visual signals that
      drive pursuit, and code commands for smooth eye movements in a three dimensional
      coordinate frame.

PMID- 14662365
TI  - Neural control of three-dimensional eye and head movements.
AB  - Although the eyes and head can potentially rotate about any three-dimensional
      axis during orienting gaze shifts, behavioral recordings have shown that certain
      lawful strategies--such as Listing's law and Donders' law--determine which axis
      is used for a particular sensory input. Here, we review recent advances in
      understanding the neuromuscular mechanisms for these laws, the neural mechanisms
      that control three-dimensional head posture, and the neural mechanisms that
      coordinate three-dimensional eye orientation with head motion. Finally, we
      consider how the brain copes with the perceptual consequences of these motor
      acts.

PMID- 14662366
TI  - The role of the thalamus in motor control.
AB  - Two characteristics of the thalamus--its apparently simple relay function and its
      daunting multinuclear structure--have been customarily viewed as good reasons to
      study something else. Yet, now that many other brain regions have been explored
      and neurophysiologists are turning to questions of how larger circuits operate,
      these two characteristics are starting to seem more attractive. First, the relay
      nature of thalamic neurons means that recording from them, like tapping into a
      wire, can reveal the signals carried by specific circuits. Second, the
      concentration of like relay neurons into nuclei means that inactivating or
      stimulating them can efficiently test the functions of the circuits. Recent
      studies implementing these principles have revealed pathways through the thalamus
      that contribute to generating movements and to monitoring one's own actions
      (corollary discharge).

PMID- 14662367
TI  - The role of primary motor cortex in goal-directed movements: insights from
      neurophysiological studies on non-human primates.
AB  - Neurophysiological studies on non-human primates have provided a large body of
      information on the response patterns of neurons in primary motor cortex during
      volitional motor tasks. Rather than finding a single simple pattern of activity
      in primary motor cortex neurons, these studies illustrate that neural activity in
      this area reflects many different types of information, including spatial goals,
      hand motion, joint motion, force output and electromyographic activity. This
      richness in the response characteristics of neurons makes estimates of any single
      variable on motor performance from population signals imprecise and prone to
      errors. It initially seems puzzling that so many different types of information
      are represented in primary motor cortex. However, such richness in neural
      responses reflects its important role in converting high-level behavioral goals
      generated in other cortical regions into complex spatiotemporal patterns to
      control not only alpha-motoneuron activity but also other features of spinal
      processing.

PMID- 14662368
TI  - Synchronous cortical oscillatory activity during motor action.
AB  - Oscillations of the motor cortex interact with similar activity of the spinal
      motoneuron pool in the 15-30 Hertz frequency range. Recent observations have
      demonstrated how this interaction affects the firing of single corticospinal
      neurons. The interaction, reflected as corticomuscular coherence, occurs for both
      distal and proximal muscles and it constitutes one connection in a larger web of
      oscillatory interactions, including several other motor areas in the cortex,
      thalamus, and cerebellum. New results cast light on the possible functional
      significance of this interaction. The rhythmic interaction may reveal interesting
      information in several motor disorders, including essential tremor, Parkinson's
      disease, myoclonus epilepsy, and mirror movements.

PMID- 14662369
TI  - Neural mechanisms of reward-related motor learning.
AB  - The analysis of the neural mechanisms responsible for reward-related learning has
      benefited from recent studies of the effects of dopamine on synaptic plasticity.
      Dopamine-dependent synaptic plasticity may lead to strengthening of selected
      inputs on the basis of an activity-dependent conjunction of sensory afferent
      activity, motor output activity, and temporally related firing of dopamine cells.
      Such plasticity may provide a link between the reward-related firing of dopamine
      cells and the acquisition of changes in striatal cell activity during learning.
      This learning mechanism may play a special role in the translation of reward
      signals into context-dependent response probability or directional bias in
      movement responses.

PMID- 14662370
TI  - Systems-level studies of movement disorders in dystonia and Parkinson's disease.
AB  - For many years pathophysiological studies on patients with movement disorders
      were viewed as inferior to those in animal models because, given the complexity
      of dealing with the complete interconnected CNS, it was difficult to assign any
      particular physiological abnormality exclusively to the site of a known lesion.
      More recently this has come to be seen as an advantage. All the articles reviewed
      below focus on how healthy parts of the CNS react to damage at a distance, with
      the result that we are now beginning to have much more insight into how these
      reactions both compensate and exacerbate the primary deficit.

PMID- 14662371
TI  - Deep brain stimulation for Parkinson's disease.
AB  - Deep brain stimulation at high frequency was first used in 1997 to replace
      thalamotomy in treating the characteristic tremor of Parkinson's disease, and has
      subsequently been applied to the pallidum and the subthalamic nucleus. The
      subthalamic nucleus is a key node in the functional control of motor activity in
      the basal ganglia. Its inhibition suppresses symptoms in animal models of
      Parkinson's disease, and high frequency chronic stimulation does the same in
      human patients. Acute and long-term results after deep brain stimulation show a
      dramatic and stable improvement of a patient's clinical condition, which mimics
      the effects of levodopa treatment. The mechanism of action may involve a
      functional disruption of the abnormal neural messages associated with the
      disease. Long-term changes, neural plasticity and neural protection might be
      induced in the network. Similar effects of stimulation and lesioning have led to
      the extension of this technique for other targets and diseases.

PMID- 14662372
TI  - Neurobiology of behaviour.

PMID- 14662373
TI  - Operant conditioning in invertebrates.
AB  - Learning to anticipate future events on the basis of past experience with the
      consequences of one's own behavior (operant conditioning) is a simple form of
      learning that humans share with most other animals, including invertebrates.
      Three model organisms have recently made significant contributions towards a
      mechanistic model of operant conditioning, because of their special technical
      advantages. Research using the fruit fly Drosophila melanogaster implicated the
      ignorant gene in operant conditioning in the heat-box, research on the sea slug
      Aplysia californica contributed a cellular mechanism of behavior selection at a
      convergence point of operant behavior and reward, and research on the pond snail
      Lymnaea stagnalis elucidated the role of a behavior-initiating neuron in operant
      conditioning. These insights demonstrate the usefulness of a variety of
      invertebrate model systems to complement and stimulate research in vertebrates.

PMID- 14662374
TI  - Route learning by insects.
AB  - Ants and other insects often follow fixed routes from their nest to a foraging
      site. The shape of an ant's route is set, initially, by navigational strategies,
      such as path integration and the ant's innate responses to landmarks, which
      depend minimally on memory. With increasing experience, these early routes are
      stabilised through the learning of views of landmarks and of associated actions.
      The substitution of memory-based strategies makes an insect's route more robust
      and precise. The ability to select between different learnt routes might incur
      additional memory requirements to those needed for performing a route, and lead
      to the associative grouping of those memories that relate to a particular route.

PMID- 14662375
TI  - Cognitive neuroethology: dissecting non-elemental learning in a honeybee brain.
AB  - The brain of a honeybee contains only 960,000 neurons and its volume represents
      only 1 mm3. However, it supports impressive behavioral capabilities. Honeybees
      are equipped with sophisticated sensory systems and have well developed learning
      and memory capacities, whose essential mechanisms do not differ drastically from
      those of vertebrates. Here, I focus on non-elemental forms of learning by
      honeybees. I show that bees exhibit learning abilities that have been
      traditionally ascribed to a restricted portion of vertebrates, as they go beyond
      simple stimulus-stimulus or response-stimulus associations. To relate these
      abilities to neural structures and functioning in the bee brain we focus on the
      antennal lobes and the mushroom bodies. We conclude that there is a fair chance
      to understand complex behavior in bees, and to identify the potential neural
      substrates underlying such behavior by adopting a cognitive neuroethological
      approach. In such an approach, behavioral and neurobiological studies are
      combined to understand the rules and mechanisms of plastic behavior in a natural
      context.

PMID- 14662376
TI  - Aggression in invertebrates.
AB  - Invertebrates are outstanding model systems for the study of aggression. Recent
      advances and promising new research approaches are bringing investigators closer
      to the goal of integrating behavioral findings with those from other disciplines
      of the neurosciences. The presence of highly structured, easily evoked behavioral
      systems offer unique opportunities to quantify the aggressive state of
      individuals, to explore the mechanisms underlying the formation and maintenance
      of dominance relationships, to investigate the dynamic properties of hierarchy
      formation, and to explore the significance of neural, neurochemical and genetic
      mechanisms in these behavioral phenomena.

PMID- 14662377
TI  - Insight into the mechanisms of neuronal processing from electric fish.
AB  - Weakly electric fish use their electric fields to locate objects and communicate
      with each other. Their electric discharges vary with species, gender, and social
      status. This variation is mediated by steroid and peptide hormones that influence
      ion currents through changes in gene expression or phosphorylation state.
      Understanding how electric fish decode the perturbations of their electric fields
      that result from interactions with the discharges of other fish or prey is
      illuminating general mechanisms of neuronal processing. Their central sensory
      circuits are specialized to process amplitude modulated signals, to detect
      microsecond variations in spike timing, and are dynamically reconfigured
      depending on the stimulus parameters.

PMID- 14662378
TI  - Neurobiology of echolocation in bats.
AB  - Echolocating bats (sub-order: Microchiroptera) form a highly successful group of
      animals, comprising approximately 700 species and an estimated 25% of living
      mammals. Many echolocating bats are nocturnal predators that have evolved a
      biological sonar system to orient and forage in three-dimensional space. Acoustic
      signal processing and vocal-motor control are tightly coupled, and successful
      echolocation depends on the coordination between auditory and motor systems.
      Indeed, echolocation involves adaptive changes in vocal production patterns,
      which, in turn, constrain the acoustic information arriving at the bat's ears and
      the time-scales over which neural computations take place.

PMID- 14662379
TI  - The gender of the voice within: the neural origin of sex differences in the
      brain.
AB  - In mammals and birds, the sex of the brain has been attributed to the action of
      gonadal hormones. In males, testosterone from the testes acts early in life to
      make the brain masculine. Studies of songbirds and rodents suggest, however, that
      male and female brain cells are intrinsically different also because of the sex
      differences in the expression of sex chromosome genes within the cells.

PMID- 14662380
TI  - Birds of a feather clock together--sometimes: social synchronization of circadian
      rhythms.
AB  - Biological systems use internal circadian clocks to efficiently organize
      physiological and behavioral activity within the 24-hour time domain. In the
      absence of time cues, circadian periods vary slightly from 24 hours, but in
      nature, ambient light serves as the most salient synchronizer for these rhythms,
      fine-tuning them to exactly 24 hours each day. For some species, social cues can
      serve to synchronize circadian rhythms in the absence of other time cues or to
      amplify ambiguous light cues. This has been demonstrated to various degrees in
      fruit flies, degus, birds, fish, bats, beavers and humans; however, studies in
      rats and hamsters have shown that social cues are less salient time cues for
      these species. Social influences on circadian timing might function to tightly
      organize the social group, thereby decreasing the chances of predation and
      increasing the likelihood of mating.

PMID- 14662381
TI  - Circannual rhythms in birds.
AB  - In many birds, reproduction, molt, migration and other seasonal activities are
      controlled by endogenous circannual rhythmicity. Under constant conditions, this
      rhythm persists for many cycles with a period deviating from 12 months. Whether
      or not the rhythm is expressed depends on day length (photoperiod), which thus
      represents an important permissive factor in the process of rhythm generation. In
      nature, circannual rhythms are usually synchronized by the seasonal changes in
      photoperiod. However, equatorial birds may use daytime light intensity, which
      changes with the annual cycle of dry and rainy seasons, as a synchronizing
      zeitgeber. Photoperiod also modulates the rate of progress of the successive
      phases of the rhythmicity, such that an optimal adjustment to the annual
      environmental cycle is guaranteed. Populations of a given species may differ in
      their responsiveness to photoperiod in a manner that can be described as
      'adaptive population-specific reaction norms'. In young migratory songbirds a
      circannual program determines changes in migratory direction and, at least
      partly, the time course and distance of migration. This circannual mechanism is
      replaced or supplemented in older birds by mechanisms formed on the basis of
      learning and memory. In general, circannual rhythms are intimately involved in
      the seasonal organization of a bird's behavior, providing the substrate onto
      which seasonal environmental factors act.

PMID- 14662384
TI  - Carbon-carbon coupling in biotransformation.
AB  - Most research on carbon-carbon coupling biocatalysts is still carried out on
      aldolases and ketolases from carbohydrate metabolism; the emphasis of these
      studies is on the synthesis of optically active compounds. A major target is to
      avoid expensive starting materials and to broaden the range of possible products.
      Protein engineering provides the basis not only for significant improvements of
      known catalysts, but also for the de novo development of new enzymes.

PMID- 14662385
TI  - New substrates for reliable enzymes: enzymatic modification of polymers.
AB  - Recent studies clearly indicate that the modification of synthetic and natural
      polymers with enzymes is an environmentally friendly alternative to chemical
      methods using harsh conditions. New processes using lipases, proteases,
      nitrilases and glycosidases have been developed for the specific non-destructive
      functionalization of polymer surfaces. The specificity of enzymes has also been
      exploited in polymer synthesis; for example, lipases have been used for the
      production of optically active polyesters. Oxidoreductases have been used for the
      cross-linking and grafting of lignaceous materials and for the production of
      polymers from phenolics. Recent successes in this area are mainly attributable to
      advances in the design of reaction systems (e.g. biphasic systems and micellar
      solutions), while the enzymes are mainly from commercial sources.

PMID- 14662386
TI  - Regeneration of cofactors for use in biocatalysis.
AB  - Cofactor-dependent enzymes catalyze many synthetically useful reactions. The high
      cost of cofactors, however, necessitates in situ cofactor regeneration for
      preparative applications. After two decades of research, several cofactors can
      now be effectively regenerated using enzyme or whole-cell based methods.
      Significant advances have been made in this area in the past three years and
      include the development of novel or improved methods for regenerating ATP, sugar
      nucleotides and 3-phosphoadenosine-5'-phosphosulphate. These approaches have
      found novel applications in biocatalysis.

PMID- 14662387
TI  - Protein engineering in bioelectrocatalysis.
AB  - Electrochemistry of redox proteins is a broadly applicable technology with
      important applications in biosensors, biofuel cells and chemical syntheses.
      Escalating attention in this area is driven by remarkable progress in designing
      efficient interfaces for transferring electrons between electrode surfaces and
      redox proteins. Research in interface design is slowly shifting from modifying
      electrode surfaces towards the engineering of redox proteins. Protein
      engineering, which encompasses rational design, directed evolution and combined
      methods, offers many powerful methods and strategies for improving the electron
      transfer properties of redox proteins.

PMID- 14662388
TI  - Engineering of secondary metabolite pathways.
AB  - Nature produces an astonishing wealth of secondary metabolites with important
      biological functions. To access this diversity of structurally complex chemical
      compounds for industrial and biomedical applications, cells have been engineered
      to produce higher levels and/or novel compounds that were previously
      inaccessible. Recent examples of metabolic and combinatorial engineering
      illustrate different strategies for the production of secondary metabolites in
      microbial cells.

PMID- 14662389
TI  - Non-canonical amino acids in protein engineering.
AB  - Methods for engineering proteins that contain non-canonical amino acids have
      advanced rapidly in the past few years. Novel amino acids can be introduced into
      recombinant proteins in either a residue-specific or site-specific fashion. The
      methods are complementary: residue-specific incorporation allows engineering of
      the overall physical and chemical behavior of proteins and protein-like
      macromolecules, whereas site-specific methods allow mechanistic questions to be
      probed in atomistic detail. Challenges remain in the engineering of the
      translational apparatus and in the design of schemes that can be used to encode
      both canonical and non-canonical amino acids.

PMID- 14662390
TI  - Protein fragment complementation strategies for biochemical network mapping.
AB  - The organization of biochemical networks that make up the living cell can be
      defined by studying the dynamics of protein-protein interactions. To this end,
      experimental strategies based on protein fragment complementation assays (PCAs)
      have been used to map biochemical networks and to identify novel components of
      these networks. Pharmacological perturbations of the interactions can be
      observed, and the resulting pharmacological profiles and subcellular locations of
      interactions allow each gene product to be 'placed' at its relevant point in a
      network. Network mapping by PCA could be used with, or instead of, traditional
      target-based drug discovery strategies to increase the quantity and quality of
      information about the actions of small molecules on living cells and the
      intricate networks that make up their chemical machinery.

PMID- 14662392
TI  - Antibacterials: are the new entries enough to deal with the emerging resistance
      problems?
AB  - Fifty years of making analogs based on less than ten antibacterial scaffolds has
      resulted in the development and marketing of over 100 antibacterial agents but,
      with the exception of the oxazolidinone core, no new scaffolds have emerged in
      the past 30 years to address emerging resistance problems. As the support for
      antibacterial research shifts away from large pharmaceutical companies, a wave of
      biotechnology companies have pursued a diverse choice of targets resulting in
      several novel classes of agent in late-stage development. Although critical for
      certain resistance niche needs, these agents are unlikely to provide the solution
      to the requirement for a major novel scaffold class of antibacterials.

PMID- 14662393
TI  - Novel biologically active natural and unnatural products.
AB  - Natural products have been used as medicinal agents for many years. In addition,
      these compounds have served as the starting points for semisynthetic analogs with
      improved properties. This review highlights work on several classes of natural
      products and their derivatives, including both well established and emerging
      structural classes that are in, or nearing, clinical use for a variety of
      important indications.

PMID- 14662394
TI  - Evolving therapeutic paradigms for HIV and HCV.
AB  - The continued development of enabling molecular technologies that can be employed
      to better understand viral replication and the action of currently available
      therapeutic agents promises to lead to the development of the next generation of
      drugs with improved therapeutic utility against human immunodeficiency virus
      (HIV) and hepatitis C virus (HCV). New therapeutic approaches have been developed
      for treating HIV and HCV infections, but key technical and therapeutic challenges
      must be addressed to further advance treatment options in each of these areas.

PMID- 14662395
TI  - Emerging viral infections in a rapidly changing world.
AB  - Emerging viral infections in both humans and animals have been reported with
      increased frequency in recent years. Recent advances have been made in our
      knowledge of some of these, including severe acute respiratory syndrome
      associated coronavirus, influenza A virus, human metapneumovirus, West Nile virus
      and Ebola virus. Research efforts to mitigate their effects have concentrated on
      improved surveillance and diagnostic capabilities, as well as on the development
      of vaccines and antiviral agents. More attention needs to be given to the
      identification of the underlying causes for the emergence of infectious diseases,
      which are often related to anthropogenic social and environmental changes.
      Addressing these factors might help to decrease the rate of emergence of
      infectious diseases and allow the transition to a more sustainable society.

PMID- 14662396
TI  - Interplay of transcriptomics and proteomics.
AB  - Despite the obvious attractions of parallel profiling of transcripts and proteins
      on a global 'omic' scale, there are practical and biological differences involved
      in their application. Transcriptomics is now a robust, high-throughput, cost
      effective technology capable of simultaneously quantifying tens of thousands of
      defined mRNA species in a miniaturized, automated format. Conversely, proteomic
      analysis is currently much more limited in breadth and depth of coverage owing to
      variations in protein abundance, hydrophobicity, stability, size and charge.
      Nevertheless, transcriptomic and proteomic data can be compared and contrasted
      provided the studies are carefully designed and interpreted. Differential
      splicing, post-translational modifications and data integration are among some of
      the future challenges to tackle.

PMID- 14662397
TI  - Transgenic animals in inflammatory disease models.
AB  - Inflammatory diseases affect a significant portion of the population worldwide
      and have been intensely studied for several decades. The advent of transgenic
      technology has allowed researchers to study individual gene contributions to the
      pathogenesis of these diseases. This has been done using standard inflammatory
      disease models in transgenic animals and by identifying novel models through the
      spontaneous generation of disease in the transgenic animal. Recent advances have
      been made in the understanding of rheumatoid arthritis, pulmonary inflammation,
      multiple sclerosis and inflammatory bowel disease through the use of transgenic
      animals in models of human inflammatory disease.

PMID- 14662398
TI  - Drug delivery in biotechnology: present and future.
AB  - Drug delivery is becoming a whole interdisciplinary and independent field of
      research and is gaining the attention of pharmaceutical makers, medical doctors
      and industry. A targeted and safe drug delivery could improve the performance of
      some classical medicines already on the market and, moreover, will have
      implications for the development and success of new therapeutic strategies, such
      as peptide and protein delivery, glycoprotein administration, gene therapy and
      RNA interference. Many innovative technologies for effective drug delivery have
      been developed, including implants, nanotechnology, cell and peptide
      encapsulation, microfabrication, chemical modification and others. On the long
      way from the clinic to market, however, several issues will have to be addressed,
      including suitable scientific development, specific financial support as a result
      of altered scientific policy, government regulations and market forces.

PMID- 14662399
TI  - Engineering proteins that bind, move, make and break DNA.

PMID- 14662401
TI  - Storage and voiding symptoms: pathophysiologic aspects.
AB  - Lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, and
      postmicturition symptoms. Although often associated with benign prostatic
      hyperplasia (BPH), they may also occur in women. This observation, the beneficial
      effects of alpha-adrenoceptor (AR) antagonists in men with BPH and LUTS, and the
      frail correlation between LUTS, and prostatic enlargement and/or outflow
      obstruction have focused interest on the role of extraprostatic alpha-ARs in the
      pathogenesis of LUTS. It has been suggested that an upregulation of contraction
      mediating alpha-ARs and a downregulation of relaxation-mediating beta-ARs can
      contribute to LUTS generation. However, recent investigations on human bladder
      tissue could not confirm such a change. Antimuscarinic agents are effective for
      treatment of the overactive bladder, which is characterized by urge, frequency,
      urge incontinence, and nocturia (ie, LUTS). This suggests that muscarinic
      receptors are involved in the pathogenesis of LUTS, and there is recent evidence
      implicating purinergic receptors. Structural changes in the bladder, such as
      smooth muscle hypertrophy and connective tissue infiltration, are associated with
      detrusor overactivity in about 50% to 66% of patients with BPH. However, it is
      unclear whether this is caused by bladder outlet obstruction because the symptoms
      may remain in up to 33% of the patients after surgical removal of the
      obstruction. When outflow obstruction is reversed in rats, there is a subset
      (20%) that continues to have overactive voiding, despite a reversal of the
      bladder hypertrophy, suggesting that changes within the central nervous system
      may be a contributing factor. LUTS can be caused by many, often overlapping,
      pathophysiologic mechanisms, which may contribute to individual variation in
      response to treatment.

PMID- 14662402
TI  - Diagnosis and treatment of voiding symptoms.
AB  - Lower urinary tract symptoms (LUTS) are associated with lower urinary tract
      dysfunction. Symptoms are the subjective indicator of a disease or change in
      condition as perceived by the patient, caregiver, or partner and may lead the
      individual to seek help from health care professionals. LUTS are usually
      qualitative and, therefore, cannot usually be used to make a definitive
      diagnosis. LUTS also can indicate pathologies other than lower urinary tract
      dysfunction, such as urinary infection. LUTS are divided into 7 groups: storage,
      voiding (obstructive), postmicturition symptoms and 4 others. Voiding symptoms,
      which are caused by lower urinary tract obstruction, include slow stream,
      splitting or spraying, intermittency, hesitancy, straining, and terminal dribble.
      Postmicturition symptoms, which are experienced immediately after micturition,
      consist of the feeling of incomplete emptying and postmicturition dribble.
      Postmicturition dribble describes the involuntary loss of urine immediately after
      the individual has finished passing urine; in men, usually after leaving the
      toilet and in women, after rising from the toilet. Hence, postmicturition dribble
      is elicited by different situations or is considered as having different
      implications. For example, although postmicturition dribble usually implies
      incomplete emptying (voiding symptoms) in elderly men with benign prostatic
      hyperplasia, postmicturition dribble is often considered as urinary incontinence
      (a storage symptom) in many patients, even with bladder outlet obstruction. In
      such cases, detailed history taking and further evaluation, such as urinary
      flowmetry, postvoid residual volume, and comprehensive urodynamic evaluation,
      should be performed as appropriate. If no urodynamic abnormalities of either the
      detrusor or the outlet can be detected despite significant LUTS, factors
      unrelated to the lower urinary tract may be responsible for the voiding symptoms.

PMID- 14662403
TI  - Diagnosis and treatment of the overactive bladder.
AB  - Overactive bladder syndrome (OAB) is a symptomatic diagnosis based on the
      presence of urgency, with or without urge incontinence, and usually accompanied
      by frequency and nocturia, in the absence of obvious pathologic or metabolic
      disease. Initial management of OAB requires an integrated approach using
      behavioral and pharmacologic methods. Patients should be educated about the
      functioning of the lower urinary tract system, fluid and dietary management,
      timed or prophylactic voiding and bladder training regimens, the keeping of
      micturition charts or bladder diaries, and pelvic floor exercises. Although the
      effectiveness of muscarinic receptor antagonists for the treatment of OAB has
      been shown, adverse effects, such as dry mouth, constipation, and blurred vision
      have somewhat limited their usefulness. Newer agents that are more bladder
      selective have been and continue to be developed. The concept of clinical
      effectiveness-a combination of efficacy, tolerability, and compliance-can be used
      to evaluate not only how well a drug works, but also the side-effect profile and
      bothersomeness and how likely patients are to continue treatment. Patients who do
      not respond to antimuscarinic treatment of OAB may do so because of a variety of
      nonpharmacologic and pharmacologic reasons. Most cases of OAB are not cured, but
      rather the symptoms are reduced, with an associated improvement in the patients'
      quality of life. Patients who have failed behavioral and pharmacologic
      intervention may respond to neuromodulation and augmentation cystoplasty. Future
      approaches may include (1) other types of systemic pharmacologic therapy; (2)
      intravesical administration of drugs, including blockers of afferent input; (3)
      intradetrusor injection of botulinum toxin; (4) the use of tissue engineering to
      simplify augmentation cystoplasty; (5) genetic interventions to reverse
      neuroplasticity changes; and (6) combinations of these approaches.

PMID- 14662407
TI  - Editorial.

PMID- 14662404
TI  - Describing bladder storage function: overactive bladder syndrome and detrusor
      overactivity.
AB  - After a comprehensive review of terminology of lower urinary tract
      function/dysfunction, the International Continence Society (ICS) has recommended
      the use of the terms overactive bladder syndrome (OAB) and detrusor overactivity.
      Detrusor overactivity is defined as a urodynamic observation characterized by
      involuntary detrusor contractions during the filling phase that may be
      spontaneous or provoked. Detrusor overactivity is subdivided into idiopathic
      detrusor overactivity and neurogenic detrusor overactivity. Because detrusor
      overactivity is a urodynamic diagnosis, it is essential to record symptoms and
      signs during urodynamic studies to correlate them with any involuntary
      contractions. The ICS 2002 report describes 2 types of detrusor overactivity: (1)
      phasic, which may or may not lead to urinary incontinence; and (2) terminal,
      which is a single involuntary detrusor contraction that often results in complete
      bladder emptying. OAB, as defined by ICS 2002, is a new term and is a symptomatic
      diagnosis. OAB is defined as urgency, with or without urge incontinence, and
      usually with frequency and nocturia. The ICS endorsement of the term OAB
      recognizes that patients with this symptom syndrome are almost always treated by
      nonsurgical means on an empirical basis, ie, without a urodynamic confirmation of
      the presumed diagnosis, detrusor overactivity. The ICS believes that these terms
      are more intuitive and will make it easier for patients and physicians alike to
      understand. It is hoped that general use of the new ICS definitions will
      facilitate effective communications between patients and their physicians
      concerning their urologic dysfunctions.

PMID- 14662408
TI  - Management of malignant sublingual salivary gland tumors.
AB  - The majority of tumors of the sublingual gland are malignant, with adenoid cystic
      carcinoma and mucoepidermoid carcinoma being the most frequent. Many other
      malignant tumor types have also been reported. The sublingual gland anatomically
      is not a unit organ and while it is described anatomically as being confined to
      the anterior floor of the mouth, salivary tissue may be located laterally along
      the submandibular duct and posterior floor of the mouth. Diagnosis should be
      suspected when any thickening or raised lesion presents in this area and a biopsy
      performed to confirm malignancy before planning further treatment. Surgery is the
      treatment of choice, and should include an en-block resection of the anterior
      floor of mouth as a minimum, and may include a portion of mandible, as well as a
      supraomohyoid neck dissection. Adjuvant radiotherapy should be considered in most
      of the patients after surgical excision.

PMID- 14662409
TI  - Effects of snuff extract on epithelial growth and differentiation in vitro.
AB  - Snuff is a locally irritative agent causing hyperkeratinization and hyperplasia
      of the oral epithelium. The aim of the study was to investigate the effects of
      snuff on epithelial cell growth and differentiation in vitro. Three-dimensional
      HaCaT cell cultures were grown for 6, 12, 14, and 18 days in the presence of 1%
      snuff extract. Ki-67, p53 and cytokeratins (Cks) 5, 13, 10, 19, 18, involucrin
      and filaggrin were studied by means of immunohistochemistry. Ki-67 indices were
      assessed, and the results analyzed statistically. Marked morphologic changes were
      seen with advanced culture time in the snuff group, probably as a result of
      increased toxic effects. Snuff exposure decreased the percentage of Ki-67
      positive cells on days 6, 12, and 14, suggesting that snuff does not stimulate
      proliferation activity in this in vitro model. Cornification-related Ck 10
      decreased after snuff exposure, indicating disturbances in the epithelial
      differentiation process.

PMID- 14662410
TI  - Expression of vascular endothelial growth factor A, B, C, and D in oral squamous
      cell carcinoma.
AB  - Vascular endothelial growth factor (VEGF) A is known to play an important role in
      tumor angiogenesis. The additional members of the VEGF family, VEGF B, C and D
      have been discovered. VEGF C and D show some selectivity toward lymphatic
      endothelial cells. However, whether VEGF family members play a role in tumor
      angiogenesis and lymph node metastasis is largely unknown. The aim of the present
      study was to explore the role of VEGF family members in oral squamous cell
      carcinoma (OSCC). We evaluated the expression of VEGF family members by
      immunohistochemistry, reverse transcription-polymerase chain reaction, and
      western blotting. All VEGF members were expressed at different levels in OSCC.
      Immunohistological analysis of VEGF family members expression and microvessel
      density revealed a correlation between VEGF A and B expression and tumor
      angiogenesis. Although VEGF A and B expression were detected in both node
      positive and node-negative OSCC, VEGF C and D expression was detected frequently
      in node-positive tumors compared to node-negative tumors. These findings suggest
      a possible relationship between the expression level of VEGF C and/or D and
      development of lymphatic tumor spread.

PMID- 14662411
TI  - Heme oxygenase-1 expression predicts cervical lymph node metastasis of tongue
      squamous cell carcinomas.
AB  - Heme oxygenase-1 (HO-1) is known as a stress-inducible protein. The present study
      was designed to investigate the relationship between HO-1 expression levels and
      clinical features of tongue cancer by using HO-1 responsiveness to stress as a
      clinical indicator. One-hundred and twelve biopsy samples from tongue squamous
      cell carcinomas were analyzed semiquantitatively by immunohistochemistry.
      Correlations between the expression level of HO-1 and the clinical features of
      tumors were statistically analyzed. Fifty-four cases with surgical confirmation
      of lymph node metastasis were examined for the association between cervical lymph
      node metastasis (pN) and other clinical features, including the HO-1 expression
      level, using logistic regression. The low HO-1 expression group contained
      significantly more undifferentiated samples (P=0.04) and pN positive cases
      (P=0.01) by univariate analysis. The low HO-1 expression group (odds ratio=8.49;
      95% confidence interval=1.64-44.09, P=0.01) and an endophytic shape (odds
      ratio=16.79; 95% confidence interval=1.77-159.53, P=0.01) were significantly
      associated with an increased risk of developing lymph node metastasis by
      multivariate analysis. Low HO-1 expression was associated with lymph node
      metastasis. The expression profile suggests HO-1 could be used clinically as a
      marker for tumors possessing the potential for lymph node metastasis. This method
      could prove useful as an adjuvant method to detect lymph node metastasis and may
      help reduce the number of surgeries by indicating when surgery is unnecessary.

PMID- 14662413
TI  - The effect of laminin and its peptide SIKVAV on a human salivary gland
      myoepithelioma cell line.
AB  - We have demonstrated that the basement membrane regulates the myoepithelioma. We
      are now studying the effect of laminin, a basement membrane protein, in the
      morphology of a cell line (M1) derived from human salivary gland plasmacytoid
      myoepithelioma. These cells were grown inside a three-dimensional preparation of
      laminin-1. Phenotype differences were assessed by light and transmission electron
      microscopy. In addition, we analysed the effect of a molecular domain of laminin
      1, the peptide SIKVAV, on M1 cells. This peptide was chosen because it is
      effective in cell proliferation and differentiation. M1 cells grown inside
      laminin-1 were mostly plasmacytoid-like, while cells treated by SIKVAV showed
      light and electron microscopic features of typical plasmacytoid cells. This
      peptide also modulated smooth-muscle actin expression in M1 cells. We
      demonstrated that laminin-1 and its derived peptide SIKVAV morphoregulates
      myoepithelioma cells in culture.

PMID- 14662412
TI  - Expression of SGLT-1 in preneoplastic and neoplastic lesions of the head and
      neck.
AB  - Tumors show an increased glucose uptake that is mediated by glucose transport
      proteins. We have analyzed the expression of the sodium-dependent glucose co
      transporters SGLT-1 and-2 in short-term cultures of squamous cell carcinomas of
      the head and neck (HNSCC) by RT-PCR. Distribution of the SGLT-1 protein in HNSCC
      tissues was investigated by immunohistochemistry. While we observed in 17/36
      HNSCC short-term cultures the SGLT-1 mRNA, we found no SGLT-2 expression. SGLT-1
      mRNA expression occurred preferentially in cultures originating from moderately
      and well differentiated HNSCC. In tumor tissues a heterogeneous SGLT-1 staining
      restricted to differentiated tumor cells was seen in 27/30 HNSCC analyzed. In
      normal mucosa SGLT-1 staining was also confined to differentiated compartments
      and lacked in dysplastic areas. Our data indicate a differentiation-dependent
      expression of SGLT-1 in HNSCC. This is important knowledge for the planning of
      glucose-targeting therapies and suggest SGLT-1 as a differentiation marker in
      head and neck tissues.

PMID- 14662414
TI  - Gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor tyrosine kinase
      inhibitor, up-regulates p27KIP1 and induces G1 arrest in oral squamous cell
      carcinoma cell lines.
AB  - High expression of epidermal growth factor receptor (EGFR) is frequently observed
      in many solid tumor types including oral squamous cell carcinomas (OSCC).
      Recently, the results of preclinical studies and early clinical trials targeting
      the EGFR have shown evidence of the activity. In this study, gefitinib ('Iressa',
      ZD1839), an EGFR-tyrosine kinase inhibitor, inhibited cell proliferation and
      upregulated p27KIP1 in OSCC cells. Growth inhibition was observed in OSCC
      xenografts when mice were treated with gefitinib in vivo. A flow cytometric
      analysis demonstrated that treatment with gefitinib induced accumulation in G1
      phase, accompanied by a decrease in the percentage of cells in S phase. Apoptosis
      was not seen in this study. Cell growth was inhibited by an increase of the cell
      cycle inhibitor p27KIP1 and a decrease of its ubiquitin ligase subunit Skp2.

PMID- 14662415
TI  - GSTM1 polymorphism and oral squamous cell carcinoma.
AB  - We investigated the frequency of the GSTM1 genotypes in 70 Brazilian patients
      with oral squamous cell carcinoma (OSCC) and 82 age-sex matched controls. The
      GSTM1 genotypes were studied by PCR-based methods. The frequency of male patients
      with OSCC and null for the GSTM1 (70.5%) was statistically different from the
      male patients from the control group (48.5%) (Odds Ratio, OR=2.53, 95% CI=1.22
      5.24, P<0.05). The frequency of the GSTM1 null genotype (0/0) in the group with
      OSCC (65.7%) was statistically different from the controls (48.7%) (OR=2.01, 95%
      CI=1.04-3.88, P<0.05). The prevalence of GSTM1 deficiency (null) was
      significantly higher for patients with oral cancer of the floor of the mouth
      (OR=3.67, 95% CI=1.11-12.11, P<0.05). In conclusion, the GSTM1 null genotype may
      increase the risk for OSCC development.

PMID- 14662416
TI  - Surveillance of basaloid oral squamous cell carcinoma: the value of [18F]FDG-PET.
AB  - Basaloid squamous cell carcinoma (BSCC) represents a rare but exceptionally
      aggressive variant of oral cancer. Hence, when tumors have been characterized to
      belong to this specific high-risk subpopulation, it remains an open issue how to
      manage the patients in terms of diagnostic surveillance and reconstruction.
      Therefore we explored whether glucose metabolism as measured by [18F]FDG-PET can
      accurately assess the disease status in the follow up of oral BSCC. The data of
      four patients with pathologically proven BSCC were analyzed in this study. These
      patients had [18F]FDG-PET scans after curative therapy to screen for local
      recurrence or disease generalization. The [18F]FDG-PET findings were correlated
      with clinical outcome. [18F]FDG-PET identified a site of recurrent tumor that was
      invisible to morphological imaging. None of the three patients with a normalized
      pattern of glucose uptake had secondary tumor progress within the further follow
      up period. Thus, [18F]FDG-PET proved valuable to identify those patients who will
      profit from early onset of reconstruction measures even though they originally
      belonged to a high-risk population.

PMID- 14662417
TI  - Effect of 5-fluorouracil on G1 phase cell cycle regulation in oral cancer cell
      lines.
AB  - 5-fluorouracil (5-FU) has been widely used for chemotherapy of head and neck
      cancer, and is known to affect the cell cycle and induce apoptotic death of
      cancer cells. However, the molecular actions of 5-FU on the cell cycle regulatory
      mechanism have not been fully explained. Herein we analyzed the effects of 5-FU
      on the expression of G1/S-related cell cycle regulators in oral cancer cell
      lines. In vitro 5-FU treatment of oral cancer cells resulted in an increase in
      G1/S phase cells. p21 expression was augmented by 5-FU without any notable
      changes in p53 expression. A remarkable up-regulation of cyclin E and a
      concomitant down-regulation of cyclin D were observed after 24 h 5-FU treatment.
      Our results suggest that 5-FU-induced changes in cell cycle regulation of oral
      cancer cells might associate with an alteration of G1 cyclins expression. p21 was
      remarkably up-regulated, but it was speculated that its activity might be
      cancelled by an increased binding to CDK4.

PMID- 14662418
TI  - Trends of oral and oropharyngeal cancer survival over five decades in 3267
      patients treated in a single institution.
AB  - The objective of this study was to analyze the influence of changes in the
      treatment on the prognosis of patients treated over 44 years in a single
      institution. The 5-decade trends in treatment approach and 5-year survival of
      3267 patients treated between 1953 and 1997 were analyzed. An increase was
      observed in primary surgical treatment and its association with radiotherapy. In
      the 1950s, 29.1% of the patients were treated by surgery, 54.5% by radiotherapy
      and 16.4% by combined treatment; in the 1990s, these proportions were 39.7, 9.7
      and 50.6%, respectively (P<0.001). There was a significant increase in the 5-year
      survival rates from 28.7% for patients treated in the 1950s to 43.2% in the 1990s
      (P<0.001). The changes in treatment approach for oral and oropharyngeal cancer
      over the last 5 decades, with an increase of surgical treatment and its
      combination with radiotherapy significantly improved the survival rates.

PMID- 14662419
TI  - Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a
      follow-up study in an Italian population.
AB  - The most important complication of oral lichen planus (OLP) is the development of
      oral squamous cell carcinoma (OSCC) but this is a very controversial matter. The
      aim of the study was to estimate in a Northern Italian cohort of OLP patients the
      risk for OSCC. Four hundred and two patients with histologically confirmed OLP
      diagnosed from January 1988 to July 1999, were followed-up to the end of February
      2001. The standardized incidence ratio (SIR) of OSCC was calculated for the
      entire cohort and specific for gender, type of OLP, therapy for OLP and hepatitis
      C virus (HCV) infection. The relative risk (RR) of OSCC according to HCV
      infection was also estimated in the cohort. During the follow-up period, two men
      (1.3%) and seven women (2.9%) developed an OSCC. The SIR was 44.9 (95% CI: 20.5
      85.2), being higher among women, but statistically significant in both genders.
      The RR of OSCC for patients with HCV as compared with those without HCV infection
      was 3.16 (0.8-12.5). Patients with OLP had a significantly increased risk of
      OSCC, irrespective of the clinical type of OLP and therapy. HCV infection
      apparently increased the risk for OSCC although this result could reflect the
      role of confounders, such as liver cirrhosis.

PMID- 14662420
TI  - Glutathione S-transferase M1 or T1 null genotype as a risk factor for developing
      multiple primary neoplasms in the upper aero-digestive tract, in Indian males
      using tobacco.
AB  - In this study conducted amongst Indian male tobacco users with upper aero
      digestive tract (UADT) squamous carcinoma, 30 patients with multiple primary
      neoplasms (MPN) were compared with 28 age and sex matched patients with a single
      primary neoplasm (SPN) for various environmental factors (form of tobacco use,
      alcohol, radiotherapy for index cancer) and genetic parameters (family history of
      UADT cancers and GSTT1/GSTM1 genotype). The GSTM1/T1 null genotype, seen in 60%
      patients with MPN versus 33% patients with SPN (P=0.03) had an odds ratio of 3.7
      [CI=1.14-11.99; P=0.03] for developing MPN. Tobacco use in the form of smoking
      with or without chewing, as opposed to only chewing, and regular alcohol intake
      were the two other factors with almost three fold increased risk for the
      development of MPN, although, the effect was not statistically significant. All
      three patients with a family history of UADT cancer developed MPN, suggesting an
      inherited predisposition.

PMID- 14662421
TI  - Lymph node metastasis in lower lip squamous cell carcinoma in relation to tumour
      size, histologic variables and p27Kip1 protein expression.
AB  - We studied a consecutive series of 95 patients undergoing radical surgical
      resection of lower lip squamous cell carcinoma (LLSCC) to assess the correlation
      between lymph node status and several prognostic variables, such as sex and age,
      tumour size, histologic grading, maximal microscopic tumour thickness, perineural
      infiltration and p27Kip1 protein status, to see which of these might be
      predictive of the development of lymph node metastases. Statistical analysis
      demonstrated a significant association between node status and tumour size,
      histological grading, maximal thickness, perineural invasion and p27Kip1 protein
      expression; additionally to node metastasis, low p27Kip1 protein expression was
      significant correlated with high microscopic thickness. These results indicate
      that lower lip squamous cell carcinomas of >2 cm, with G3-G4 histological
      grading, maximal thickness of >6 mm, perineural invasion and low p27Kip1 protein
      expression (LI<19.7%) are at high risk for the development of lymph node
      metastases.

PMID- 14662422
TI  - Severe atherosclerosis of the radial artery in a free radial forearm flap
      precluding its use.
AB  - The free radial forearm flap is the most frequently used free flap for head and
      neck reconstructions. Survival of free flaps is dependent on adequate blood
      supply. A 69-year old woman was scheduled for excision of a T3N0M0 oropharyngeal
      carcinoma, neck dissections and reconstruction with a free vascularized radial
      forearm flap. During the operation it appeared that the entire radial artery was
      almost completely obstructed by atherosclerotic plaques precluding microvascular
      anastomosis. Despite systemic risk factors certain artery types are more prone to
      develop clinically manifest atherosclerosis. There are no reports on the
      pathology of the radial artery in free flap reconstructions. In head and neck
      cancer patients severe atherosclerosis of the radial artery is very rare, but if
      present makes free radial forearm flap reconstruction impossible. Therefore, in
      patients with risk factors for peripheral vascular disease screening for radial
      artery stenosis should be considered.

PMID- 14662425
TI  - Passive commitment.

PMID- 14662423
TI  - Primary B-cell lymphoma of the tongue in a patient with systemic sclerosis.
AB  - We report a patient with systemic sclerosis who had the unusual development of a
      large-cell B-cell lymphoma of the base of his tongue. Patients with systemic
      sclerosis display an increased incidence of malignant neoplasms, particularly,
      breast and lung carcinomas [Arthritis. Rheum. 36 (1993) 460; Ann. Rheum. Dis. 52
      (1993) 531]. The description of this case adds further evidence to the possible
      interrelationship of systemic sclerosis and the development of malignant
      neoplasms. A careful review of the English medical literature disclosed that B
      cell lymphoma of the tongue in a patient with systemic sclerosis is an
      association which has not been described previously.

PMID- 14662426
TI  - Throwing a wrench in the works?

PMID- 14662427
TI  - Getting to grips with gefitinib.

PMID- 14662428
TI  - Anticancer therapy targeting the apoptotic pathway.
AB  - Apoptosis, or programmed cell death, has an essential role in controlling cell
      number in many developmental and physiological settings and in chemotherapy
      induced tumour-cell killing. It is a genetically regulated biological process,
      guided by the ratio of proapoptotic and antiapoptotic proteins. Recently,
      inducers of apoptosis have been used in cancer therapy. Several studies have
      attempted to induce apoptosis by triggering the tumour-necrosis-factor-related
      apoptosis-inducing ligand receptor and the BCL2 family of proteins, and others
      have targeted the caspases, and proteins that inhibit apoptosis. Most of these
      therapies are still in preclinical development because of their low efficacy and
      susceptibility to drug resistance, but some of them have shown promising results.
      In this article, we review the development and clinical efficacy of proapoptotic
      drugs that have shown promise.

PMID- 14662429
TI  - Part I: testicular cancer--management of early disease.
AB  - For patients diagnosed with early-stage testicular cancer radical orchidectomy is
      the primary therapeutic intervention. The major pathological types of testicular
      cancer are seminoma and non-seminomatous germ-cell cancer. After orchidectomy,
      most patients with seminoma receive adjuvant radiotherapy as standard of care,
      although surveillance and adjuvant chemotherapy protocols are being developed.
      For patients with non-seminomatous tumours there are three therapeutic options;
      surveillance, adjuvant chemotherapy, or retroperitoneal lymph-node dissection.
      These patients are classified into groups with high-risk or low-risk of
      recurrence by presence of vascular invasion in the surgical specimen. After
      orchidectomy, about 50% of patients with high-risk disease will relapse but this
      risk is reduced to less than 5% with adjuvant therapy. Surveillance of patients
      with low-risk disease is acceptable because testicular cancer is still curable if
      metastatic recurrence occurs. There is no consensus about the management of early
      non-seminomatous testicular cancer because survival is almost 100% irrespective
      of the initial treatment decision.

PMID- 14662430
TI  - Part II: testicular cancer--management of advanced disease.
AB  - Up to 80% of metastatic germ-cell tumours are curable with conventional
      chemotherapy. The combination of cisplatin, bleomycin, and etoposide has become
      the gold standard in this disease. Patients can be divided into good,
      intermediate, and poor prognosis groups. For those patients with good prognostic
      features, cure rates reach 90% and attempts have been made to reduce toxic
      effects of treatment while maintaining efficacy. Patients that relapse require
      salvage treatment. This can involve the incorporation of drugs such as ifosfamide
      and taxol into conventional protocols or the use of high-dose chemotherapy with
      stem-cell transplants. Patients with poor prognosis disease are much more likely
      to fail conventional chemotherapy and are candidates for dose-intensive protocols
      or transplants as first-line treatment. Although the results obtained in treating
      metastatic germ-cell tumours are superior to those with other solid tumour types,
      there are still many areas that require further improvement.

PMID- 14662431
TI  - Palliative therapy of disseminated malignant melanoma: a systematic review of 41
      randomised clinical trials.
AB  - We undertook a systematic review of 41 randomised studies in disseminated
      melanoma, identified by a comprehensive search. We aimed to investigate rates of
      response to various treatment modalities and the outcome for the patients. We
      analysed seven studies that compared polychemotherapy with single-agent
      dacarbazine, six that compared different chemotherapeutic schedules with each
      other, five on the addition of tamoxifen to a reference therapy, and six that
      included non-specific immunostimulators. In 17 studies, the addition of
      interferon alfa, interleukin 2, or both, to a reference therapy was investigated,
      including trials with biochemotherapy. Many trials had small sample sizes and did
      not report a power analysis; not all were analysed by intention to treat.
      Although some treatment regimens, especially polychemotherapeutic schedules, seem
      to increase response rates, none of the treatment schedules was proven to prolong
      overall survival. Patients with disseminated melanoma should be treated with well
      tolerated drug regimens, such as single-agent treatments or in combination with
      interferon alfa. Systemic treatments should preferably be investigated in
      randomised trials so that the potential benefits of new treatment concepts can be
      thoroughly examined.

PMID- 14662432
TI  - Correlation of MRI/PET rim enhancement in breast cancer: a delivery related
      phenomenon with therapy implications?

PMID- 14662433
TI  - Excisional surgery for cancer cure: therapy at a cost.
AB  - Excisional surgery is one of the primary treatment modalities for cancer. Minimal
      residual disease (MRD) is the occult neoplastic disease that remains in situ
      after curative surgery. There is increasing evidence that tumour removal alters
      the growth of MRD, leading to perioperative tumour growth. Because neoplasia is a
      systemic disease, this phenomenon may be relevant to all patients undergoing
      surgery for cancer. In this review we discuss the published work that addresses
      the effects of tumour removal on subsequent tumour growth and the mechanisms by
      which tumour excision may alter residual tumour growth. In addition, we describe
      therapeutic approaches that may protect patients against any oncologically
      adverse effects of tumour removal. On the basis of the evidence presented, we
      propose a novel therapeutic paradigm; that the postoperative period represents a
      window of opportunity during which the patient may be further protected against
      the oncological effects of tumour removal.

PMID- 14662434
TI  - Identification and high-resolution mapping of a constitutional 11q deletion in an
      infant with multifocal neuroblastoma.

PMID- 14662435
TI  - Periodic funny turns.

PMID- 14662439
TI  - The true logic of this world.

PMID- 14662440
TI  - Physiology and disorders of oculomotor and vestibular control. Proceedings of the
      Third International Ocular Motor Meeting. Waldbad Kreuth, Germany. April 3-5,
      2003.

PMID- 14662441
TI  - The spa at Kreuth, or why did the Russian czars visit there?

PMID- 14662442
TI  - Physiology of the eyelid motor system.
AB  - The eyelid motor system represents an excellent experimental model for the study
      of reflex and learned motor responses. Eyelid responses can be recorded
      quantitatively with the search coil in a magnetic-field technique. Stimuli able
      to evoke reflex blinks (air puffs, flashes of light, tones) can also be
      controlled quantitatively. Eyelid movements can be classified as spontaneous,
      passive (such as those following eye saccades), reflex, and acquired with
      classical conditioning procedures. Information is available regarding the firing
      activity of brainstem motoneuronal pools (abducens, accessory abducens, and
      facial motoneurons) involved in these types of eyelid response. In particular,
      facial motoneurons present different encoding properties for the generation of
      reflex against learned eyelid responses. In cats, accessory abducens motoneurons
      are involved only in reflex (but not in learned) blinks. The recent description
      of the complete organization of premotoneuronal pathways related to eyelid
      motorics opens new experimental possibilities for the study of this particular
      motor system.

PMID- 14662443
TI  - Development of the optokinetic response in macaques: a comparison with cat and
      man.
AB  - In macaque monkeys, an optokinetic response (OKR) can be elicited monocularly
      both in temporonasal and, albeit weaker, in nasotemporal direction very early
      after birth. The further maturation of equal strengths of OKR in both directions
      depends on stimulus velocity: at low-stimulus velocities (10-20 degrees /s)
      symmetry is reached at 3-4 weeks of age, at higher-stimulus velocities (40-80
      degrees /s) it is reached only at 4-5 months of age. Retinal slip neurons in the
      NOT-DTN are direction selective for ipsiversive stimulus movement shortly after
      birth. Most of these neurons receive input from both eyes; many are dominated by
      the contralateral eye. Electrophysiological and neuroanatomical evidence suggests
      that the cortical input to the NOT-DTN starts to become functional by postnatal
      day 14, at the latest. Based on these behavioral and physiological data, as well
      as on comparison with data from kittens and human infants, we hypothesize that
      the very early monocularly elicited bidirectional optokinetic response is due to
      the direct retinal input from both eyes to the NOT-DTN. As the cortical
      projection matures, it gains more and more influence upon the response properties
      of retinal slip neurons in the NOT-DTN, and the retinal influence gradually
      decreases.

PMID- 14662444
TI  - GABAergic neurons in the rostral mesencephalon of the macaque monkey that control
      vertical eye movements.
AB  - The mesencephalic reticular formation is important for the generation of vertical
      eye movements, but up until now the location of inhibitory premotor neurons is
      not known in primates. With tract-tracer methods combined with
      immunocytochemistry or in situ hybridization, we investigated the location of
      GABAergic premotor neurons in the rostral interstitial nucleus of the medial
      longitudinal fascicle (riMLF) and interstitial nucleus of Cajal (iC) in macaque
      monkeys. In the present work, only the premotor pathways of the downward pulling
      eye muscles, superior oblique (SO) and inferior rectus (IR), were studied. We
      found that very few, small GABAergic neurons are present in the riMLF, and none
      of them was found to project to the oculomotor nuclei, suggesting the presence of
      exclusively excitatory projections from the riMLF to the oculomotor neurons.
      However, in the iC, medium-sized and large GABAergic neurons were identified
      projecting contralaterally to the SO and IR motoneurons, and presumably the iC of
      the other side. These commissural GABAergic projections are well suited to
      inhibit the SO and IR motoneurons and possibly premotor down-burst-tonic neurons
      during upward eye movements.

PMID- 14662445
TI  - Shared brainstem pathways for saccades and smooth-pursuit eye movements.
AB  - A long-standing belief holds that the saccadic and smooth-pursuit eye movement
      systems are composed of largely separate premotor circuits, at least in the
      brainstem. One crucial prediction predicated on this belief is that the tonic
      discharge of omnipause neurons (OPNs), which are thought to be part of only the
      saccadic system, should not be modulated during pursuit eye movements. This
      report shows that the discharge of OPNs, in contradiction, is modulated downward
      during pursuit movements. In contrast to their behavior during saccades, where
      they pause completely for the duration of the movement, the downward modulation
      during pursuit did not totally silence OPNs. The depth of the downward modulation
      was correlated with the speed of the ongoing pursuit movement. Another type of
      cell, which we have named saccade/pursuit neurons, was recorded in the paramedian
      pontine reticular formation near the location of OPNs. This subpopulation of
      burst cells discharged a cascade of spikes for saccades in a preferred direction.
      They also displayed a lower-frequency sustained discharge of spikes for the
      duration of pursuit in the same preferred direction. These data suggest a new
      type of combined model for the organization of the brainstem saccade/pursuit
      system. In this new combined model, the OPNs form a common inhibitory mechanism
      for both types of movements, and the saccade/pursuit neurons participate in the
      eye-velocity modulation of OPN discharge or membrane polarization during either
      type of movement.

PMID- 14662446
TI  - Motor and sensory innervation of extraocular eye muscles.
AB  - Eye muscles are unusual in several ways; one is that they have up to three
      different layers-the inner global layer, the outer orbital layer, and in some
      species an external marginal layer has been described. In sheep this is called
      the "peripheral patch layer." Three different types of proprioceptors are found
      in eye muscles-muscle spindles, Golgi tendon organs, and palisade endings. A
      survey of the organization of their location leads us to the hypothesis that each
      receptor is confined to a separate layer of the eye muscle. The palisade endings
      are associated with the global layer, the muscle spindles lie predominantly in
      the orbital layer, and the Golgi tendon organs are found only in the peripheral
      patch layer. This well-organized scheme may help us to understand the
      proprioceptive system in eye muscles.

PMID- 14662447
TI  - Activity-related postlesional vestibular reorganization.
AB  - The synaptic convergence patterns of semicircular canal and macular afferent
      nerve inputs onto second-order vestibular neurons reorganize in adult frogs after
      a change in the activity of vestibular nerve afferent fibers. Axotomized afferent
      nerve fibers become silent after a vestibular nerve lesion, and second-order
      vestibular target neurons become disfacilitated. These changes initiate an
      activity-related process that was studied in detail in vitro two months after a
      section of the ramus anterior (RA) of N. VIII. The postlesional reaction results
      in an expansion of signals, preferentially from intact, remaining afferent nerve
      fibers, but also from excitatory commissural and spinal ascending fibers. This
      process of expansion takes weeks, is graded in its extent, and reversible in case
      of a nerve regeneration, but is not competitive, i.e., the synaptic contacts from
      axotomized afferent nerve fibers are maintained without a change in their
      efficacy. Postlesional synaptic reorganization in the brainstem is restricted to
      the operated side, underlies the improved responsiveness of disfacilitated second
      order vestibular neurons, but also their altered spatial response tuning. The
      functional consequences of this reorganization were studied in vivo two months
      after RA nerve section by recording abducens nerve responses during linear or
      angular accelerations. The vector orientations of best responses of the abducens
      nerve of chronic RA frogs evoked by linear or angular acceleration differed from
      the vector orientations of controls. In chronic RA frogs, linear acceleration
      evoked contralesional abducens nerve responses that originated from the utricle
      on the intact side and from the lagena, a vertical macular organ in frogs. Such
      an inadequate lagenar response component was absent in controls and in the ipsi
      lesional abducens nerve of chronic RA frogs. Similar differences were detected in
      the direction of abducens nerve responses of chronic RA frogs during angular
      acceleration. Thus, compensatory vestibulo-ocular reflexes of chronic RA frogs
      became more symmetric in gain, but less precise in direction.

PMID- 14662448
TI  - Discharge patterns of cerebellar output neurons in the caudal fastigial nucleus
      during head-free gaze shifts in primates.
AB  - Lesion studies in both human and non-human primates indicate that the cerebellum
      is important for accurate and stereotyped saccadic eye movements. Based on single
      unit recordings and pharmacological inactivations in head-fixed monkeys, we
      suggested that the caudal fastigial nucleus (CFN) provides the brainstem saccade
      generator with a burst that helps accelerate contraversive saccades and
      decelerate ipsiversive ones. Here we examine this suggestion during head-free
      gaze shifts where there can be a 10-fold difference in saccade duration. First,
      the timing of the burst does not depend on whether the gaze shift has a head
      component. When a family of either ipsiversive or contraversive gaze shifts with
      a variety of saccadic durations is aligned on gaze onset, the high-frequency
      burst in the associated rasters occurs progressively later as saccade duration
      increases. Realignment of the same rasters with the end of the saccade reveals a
      tight timing of burst end with saccade end for all 10 CFN burst neurons studied.
      The delayed bursts for contraversive saccades were unexpected based on the early
      burst illustrated in the published head-fixed data. One hypothesis is that the
      late activity helps terminate contraversive as well as ipsiversive gaze shifts.
      An alternative explanation is that the late CFN burst could still be used as an
      excitatory drive to promote the late reacceleration or prolonged velocity plateau
      that is present during large gaze shifts.

PMID- 14662449
TI  - Adaptation of saccadic eye movements: transfer and specificity.
AB  - The present study was designed to test whether the adaptation of saccadic eye
      movements depends only on the eye displacement vector of the trained saccade or
      also on eye position information. Using the double-step target paradigm in eight
      human subjects, we first induced in a single session two "opposite directions
      adaptations" (ODA) of horizontal saccades of the same vector. Each ODA (backward
      or forward) was linked to one vertical eye position (12.5 degrees up or 25
      degrees down) and alternated from trial to trial. The results showed that
      opposite changes of saccade amplitude can develop simultaneously, indicating that
      saccadic adaptation depends on orbital eye position. This finding has important
      functional implications because in everyday life our eyes saccade from constantly
      changing orbital positions. A comparison of these data to two control conditions
      in which training trials of a single type (backward or forward) were presented at
      both 12.5 degrees and -25 degrees eye elevations further indicated that eye
      position specificity is complete for backward, but not for forward, adaptation.
      Finally, the control conditions also indicated that the adaptation of a single
      saccade fully transferred to untrained saccades of the same vector, but initiated
      from different vertical eye positions. In conclusion, our study indicates that
      saccadic adaptation mechanisms use vectorial eye displacement signals, but can
      also take eye position signals into account as a contextual cue when the training
      involves conflicting saccade amplitude changes.

PMID- 14662450
TI  - Adaptive changes in the angular VOR: duration of gain changes and lack of effect
      of nodulo-uvulectomy.
AB  - Alterations in the gain of the vertical angular vestibulo-ocular reflex (VOR) are
      dependent on the head position in which the gain changes were produced. We
      determined how long gravity-dependent gain changes last in monkeys after four
      hours of adaptation, and whether the adaptation is mediated through the nodulus
      and uvula of the vestibulocerebellum. Vertical VOR gains were adaptively modified
      by rotation about an interaural axis, in phase or out of phase with the visual
      surround. Vertical VOR gains were modified with the animals in one of three
      orientations: upright, left-side down, or right-side down. Monkeys were tested in
      darkness for up to four days after adaptation using sinusoidal rotation about an
      interaural axis that was incrementally tilted in 10 degrees steps from vertical
      to side down positions. Animals were unrestrained in their cages in normal light
      conditions between tests. Gravity-dependent gain changes lasted for a day or less
      after adaptation while upright, but persisted for two days or more after on-side
      adaptation. These data show that gravity-dependent gain changes can last for
      prolonged periods after only four hours of adaptation in monkeys, as in humans.
      They also demonstrate that natural head movements made while upright do not
      provide an adequate stimulus for rapid recovery of vertical VOR gains that were
      induced on side. In two animals, the nodulus and uvula were surgically ablated.
      Vertical gravity-dependent gain changes were not significantly different before
      and after surgery, indicating that the nodulus and uvula do not have a critical
      role in producing them.

PMID- 14662451
TI  - Short-term adaptation of the VOR: non-retinal-slip error signals and saccade
      substitution.
AB  - We studied short-term (30 min) adaptation of the vestibulo-ocular reflex (VOR) in
      five normal humans using a "position error" stimulus without retinal image
      motion. Both before and after adaptation a velocity gain (peak slow-phase eye
      velocity/peak head velocity) and a position gain (total eye movement during chair
      rotation/amplitude of chair motion) were measured in darkness using search coils.
      The vestibular stimulus was a brief ( approximately 700 ms), 15 degrees chair
      rotation in darkness (peak velocity 43 degrees /s). To elicit adaptation, a
      straight-ahead fixation target disappeared during chair movement and when the
      chair stopped the target reappeared at a new location in front of the subject for
      gain-decrease (x0) adaptation, or 10 degrees opposite to chair motion for gain
      increase (x1.67) adaptation. This position-error stimulus was effective at
      inducing VOR adaptation, though for gain-increase adaptation the primary strategy
      was to substitute augmenting saccades during rotation while for gain-decrease
      adaptation both corrective saccades and a decrease in slow-phase velocity
      occurred. Finally, the presence of the position-error signal alone, at the end of
      head rotation, without any attempt to fix upon it, was not sufficient to induce
      adaptation. Adaptation did occur, however, if the subject did make a saccade to
      the target after head rotation, or even if the subject paid attention to the new
      location of the target without actually looking at it.

PMID- 14662452
TI  - Adaptations and deficits in the vestibulo-ocular reflex after peripheral ocular
      motor palsies.
AB  - Palsy of a nerve might be expected to lower vestibulo-ocular reflex (VOR)
      responses in its fields of motion, but effects of peripheral neuromuscular
      disease were unknown. We recorded the VOR during sinusoidal head rotations in
      yaw, pitch, and roll at 0.5-2 Hz and static torsional gain in 43 patients with
      unilateral nerve palsies. Sixth nerve palsy (n = 21) reduced both abduction and
      adduction VOR gains in darkness. In light, horizontal visually enhanced VOR
      (VVOR) gains were normal in moderate and mild palsy. In severe palsy, horizontal
      VVOR gains remained low in the paretic eye when it was fixating, whereas gains in
      the nonparetic eye became higher than normal. Third nerve palsy (n = 10)
      decreased VOR and VVOR gains during abduction, adduction, elevation, depression,
      extorsion, and intorsion. Fourth nerve palsy (n = 13) reduced VOR gains of the
      paretic eye during intorsion, extorsion, elevation, depression, abduction, and
      adduction, but in light vertical and horizontal VVOR gains were normal. In the
      nonparetic eye, all gains were normal. Reduced VOR gains in the direction of
      paretic muscles and also in the direction of their antagonists, together with
      normal gains in the nonparetic eye, indicate a selective adjustment to the
      antagonists of paretic muscles. Increase of VVOR gains to normal in the paretic
      eye, when used for fixation, without conjugate increase in gains in the occluded
      nonparetic eye, provides further evidence of selective adaptation for the paretic
      eye. Motions of the eyes after nerve palsies indicate monocular VOR adaptation in
      three dimensions.

PMID- 14662453
TI  - Neural control of three-dimensional eye and head posture.
AB  - The neural commands for gaze control include not only signals that drive the eyes
      and head from one point to the next, but also those that hold the eyes and head
      steady at the end of each movement. Studies using microstimulation and chemical
      inactivation techniques, in head-fixed and head-free macaques, were used to
      investigate the role of the interstitial nucleus of Cajal (INC) in the production
      of the latter, tonic signals. The right INC was found to control clockwise-up and
      clockwise-down components of both eye and head orientation, whereas the left INC
      was found to control the counterclockwise-up and counterclockwise-down
      components. Temporary inactivation of the INC left the eyes and head unable to
      hold their final torsional and vertical positions after each gaze shift. Thus,
      the INC is strongly implicated in the production of the tonic, step-like commands
      that maintain eye and head orientations between gaze shifts. In addition, these
      studies also found that the INC represents the torsional and vertical commands
      for eye and head orientation using different coordinate coding strategies,
      optimally matched to the different three-dimensional postural constraints
      observed in the eye and head.

PMID- 14662454
TI  - Dynamic modulation of ocular orientation during visually guided saccades and
      smooth-pursuit eye movements.
AB  - Rotational disturbances of the head about an off-vertical yaw axis induce a
      complex vestibuloocular reflex pattern that reflects the brain's estimate of head
      angular velocity as well as its estimate of instantaneous head orientation (at a
      reduced scale) in space coordinates. We show that semicircular canal and otolith
      inputs modulate torsional and, to a certain extent, also vertical ocular
      orientation of visually guided saccades and smooth-pursuit eye movements in a
      similar manner as during off-vertical axis rotations in complete darkness. It is
      suggested that this graviceptive control of eye orientation facilitates rapid
      visual spatial orientation during motion.

PMID- 14662455
TI  - Mathematical model predicts clinical ocular motor syndromes.
AB  - Clinical ocular motor syndromes were compared with ocular motor syndromes
      simulated by a mathematical model of the vestibuloocular reflex. The mathematical
      sensorimotor feedforward model of otolith control of three-dimensional binocular
      eye position is based on relevant anatomical connections of the vestibuloocular
      reflex from the utricles to extraocular eye muscles. This is the first attempt to
      simulate static ocular motor syndromes for unilateral utricular or vestibular
      nerve failure, lesions of the vestibular nucleus, and lesions of the ascending
      vestibuloocular reflex pathways. Comparison of the predicted syndromes with those
      found in patients with unilateral disorders of the vestibular nerve (herpes
      zoster neuritis), the vestibular nucleus (medullary infarction), and the medial
      longitudinal fasciculus (pontine infarction) showed good agreement as regards the
      direction of horizontal, vertical, and torsional eye deviations. The ability of
      the model to simulate complete or incomplete failures of single elements or
      entire pathways allows us to pose direct clinical questions about as yet unknown
      ocular motor syndromes or about the localization of the damage as well as the
      mechanism involved in syndromes already known.

PMID- 14662456
TI  - Examining the paradoxical relation between number of spikes and gaze amplitude in
      abducens neurons.
AB  - During head-unrestrained gaze shifts, the number of spikes in the burst of
      abducens neurons increases with gaze amplitude, even when corrected for the
      component of the discharge related to the change in eye position. We examine this
      paradoxical dissociation between the number of spikes and eye amplitude, which
      occurs because eye amplitude in the head saturates for larger gaze shifts. First,
      we show that the extra spikes are unlikely to be due to antagonist muscle loading
      because the abducens neurons are completely silent during large gaze shifts when
      the muscle acts as an antagonist. Next, we divide the firing rate profile of
      abducens neurons into terms that represent signals related to eye position,
      velocity, and acceleration; a d.c. offset term specifying the firing associated
      with straight-ahead gaze; and a slide term, which compensates for the zero of the
      oculomotor plant. Then we examine the contribution of each term to the number of
      spikes recorded. A comparison of the number of spikes with the integral of the
      fitted function, combining all of the terms, for the duration of the burst
      reveals that the simulation captures much of the actual data. However, even a
      model with a slide term cannot reproduce the nonlinear relationship of the number
      of spikes with amplitude that characterizes large gaze shifts.

PMID- 14662457
TI  - Signal processing of semicircular canal and otolith signals in the vestibular
      nuclei during passive and active head movements.
AB  - The vestibular nerve sends signals to the brain that code the movement and
      position of the head in space. These signals are used by the brain for a variety
      of functions, including the control of reflex and voluntary movements and the
      construction of a sense of self-motion. If many of these functions are to be
      carried out, a distinction must be made between sensory vestibular signals
      related to active head movements and those related to passive head movements.
      Current evidence is that the distinction occurs at an early stage of sensory
      processing in the brain, and the results are evident in the firing behavior of
      neurons in the vestibular nuclei that receive direct inputs from the vestibular
      nerve. Several specific examples of how sensory information related to passive
      and active head movements is transformed in the vestibular nuclei are discussed.

PMID- 14662458
TI  - Morphological properties of vestibulospinal neurons in primates.
AB  - The lateral and medial vestibulospinal tracts constitute the major descending
      pathways controlling extensor musculature of the body. We examined the axon
      morphology and synaptic input patterns and targets in the cervical spinal
      segments from these tract cells using intracellular recording and biocytin
      labeling in the squirrel monkey. Lumbosacral projecting cells represent a
      private, and mostly rapid, communication pathway between the dorsal Deiters'
      nucleus and the motor circuits controlling the lower limbs and tail. The cervical
      projecting cells provide both redundant and variable synaptic input to spinal
      cell groups, suggesting both general and specific control of the head and neck
      reflexes.

PMID- 14662459
TI  - Role of the dorsolateral pontine nucleus in visual-vestibular behavior.
AB  - Visual-vestibular behavior depends on signals traveling in climbing and mossy
      fiber pathways. Our study examined the role of the dorsolateral pontine nucleus
      (DLPN), a major component of the cortico-ponto-cerebellar mossy fiber pathway.
      DLPN neurons discharge in relation to smooth pursuit and during visual
      stimulation, indicating a potential role in visually guided motor learning in the
      vestibulo-ocular reflex (VOR). We used unilateral muscimol injections to
      determine the potential role of the DLPN in short-term VOR gain adaptation.
      Preinjection adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz,
      30 degrees /s) for 2 h while the monkey viewed a stationary visual surround
      through either magnifying (x2) or minifying (x0.5) lenses. VOR gain increases (23
      32%) or decreases (22-48%) as measured in complete darkness (VORd) were achieved.
      Following DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit
      was reduced by 35-68%, and steady state gain was reduced by 32-61%. Furthermore,
      the monkey's ability to cancel the VOR was impaired. In contrast to these
      significant deficits in ipsilesional smooth pursuit, the VOR during lens viewing
      was similar to that measured in preinjection control experiments. Similarly,
      following 2 h of adaptation, VORd gain adaptation was indistinguishable from
      control adaptation values for either ipsilesional or contralesional directions of
      head rotation. Our results suggest that visual error signals for short-term
      adaptation of the VOR are derived from sources other than the DLPN, such as those
      from the accessory optic system.

PMID- 14662460
TI  - Cerebellar contribution to saccades and gaze holding: a modeling approach.
AB  - The possible role of the cerebellum for the control of saccades and gaze holding
      is reconsidered using a computational modeling approach. As suggested by previous
      research, control of gaze holding is assumed to be enhanced by the floccular
      lobe, whereas control of the saccadic pulse is governed by the oculomotor vermis
      and fastigial nucleus. In the present work, a negative feedback loop via the
      paramedian tract neurons and the floccular lobe that contains a forward model of
      the oculomotor plant is supposed to enhance the time constant of the brainstem
      integrator. Control of saccadic amplitude is hypothesized to be achieved by a
      more complex network: feedforward projections from the superior colliculus via
      the nucleus reticularis tegmenti pontis to the oculomotor vermis and fastigial
      nucleus cooperate with feedback connections from excitatory burst neurons to
      overcome the sluggishness of the assumed local feedback loop formed via the
      superior colliculus and to implement inverse dynamics of downstream neural and
      motor processing.

PMID- 14662461
TI  - Saccade dysmetria during functional perturbation of the caudal fastigial nucleus
      in the monkey.
AB  - The caudal fastigial nucleus (cFN) is the output nucleus by which the
      medioposterior cerebellum influences the brainstem saccade generator. In the
      monkey, inactivation of one cFN by local injection of muscimol impairs all
      saccades: ipsiversive saccades become hypermetric, contraversive saccades become
      hypometric, and saccades aimed at a target located in the upper or lower visual
      fields are biased horizontally toward the injected side. The pharmacological
      action of muscimol does not allow deficits that are presaccadic to be
      distinguished from those occurring during saccade execution. To determine the
      interval during which altered cFN activity affects saccade accuracy, we applied
      low-frequency electrical microstimulation (100 Hz for 100-300 ms) to the cFN of
      three monkeys while they were making saccades toward a flashed target. Similar to
      the effect of muscimol injection in cFN, low-frequency microstimulation biased
      all saccades toward the ipsilateral side. When the microstimulation was applied
      after target flash and before saccade onset, the ipsilateral bias was absent.
      However, when the stimulation was applied during the ongoing movement, the
      saccade trajectory was biased toward the stimulated side. The muscimol-like
      effect of the microstimulation suggests that the stimulation inhibits cFN
      activity, possibly by recruiting the inhibitory afferents from the cerebellar
      vermis (axons of Purkinje cells). Low-frequency microstimulation had to be
      applied during the saccade to bias its trajectory. These data suggest that the
      ipsilateral horizontal bias observed during muscimol inactivation results from an
      imbalance in the intrasaccadic activity between the two caudal fastigial nuclei.

PMID- 14662462
TI  - The role of the fastigial nucleus in saccadic eye oscillations.
AB  - For the first time, we provide functional magnetic resonance imaging evidence for
      a recent hypothesis that saccadic oscillations in opsoclonus may result from a
      disinhibition of the cerebellar fastigial nuclei. Two patients with severe
      opsoclonus were examined during fixation in the light and during eye closure and
      in darkness where opsoclonus disappeared. Their activation during opsoclonus was
      compared with 10 healthy subjects performing visually guided and self-paced
      saccades in the light and darkness. In contrast to the control subjects, the
      patients showed a strong bilateral midline cerebellar activation that involved
      the deep cerebellar nuclei. This is probably not just a secondary finding in the
      fastigial nuclei due to the high frequent saccadic activity because there was,
      concomitantly, no oculomotor vermal activation, which is normally seen in healthy
      subjects. We propose that cerebellar activation of the fastigial nuclei may cause
      opsoclonus via their projections to the brainstem saccadic generator.

PMID- 14662463
TI  - Multimodal signal integration in vestibular neurons of the primate fastigial
      nucleus.
AB  - The rostral fastigial nucleus contains vestibular neurons, which presumably are
      involved in spinal mechanisms (neck, gait, posture) and which are not modulated
      with individual eye movements. Single-unit recordings in the alert behaving
      monkey during natural stimulus conditions reveal that virtually all neurons
      demonstrate integration of several sensory inputs. This applies not only for
      canal-canal and canal-otolith interaction, but also for otolith-otolith
      interaction. There is also some evidence that most neurons receive not only an
      utriculus but also a sacculus input. Furthermore, most neurons also respond to
      large-field optokinetic stimulation, reflecting visual-vestibular interaction.
      Neurons are also affected by the head on trunk position, which would allow these
      neurons to operate in a body-centered rather than a head-centered reference
      frame. These complex, multisensory features could permit fastigial nucleus
      neurons to rather specifically affect spinal motor functions.

PMID- 14662464
TI  - Discharge properties of saccade-related neurons in the primate fastigial
      oculomotor region.
AB  - To clarify the mechanisms by which the cerebellar fastigial oculomotor region
      (FOR) contributes to the control of saccadic eye movements, we recorded saccade
      related FOR units in alert monkeys that made horizontal saccades between
      neighboring points of a three-by-three grid of target positions (16 degrees
      amplitude). As in previous studies, FOR units exhibited saccade-related bursts
      that occurred earlier for contralateral than for ipsilateral saccades. In
      addition, many FOR units reflected variations in the kinematic profiles of the
      saccades by exhibiting bursts with earlier onset and shorter peak latencies and
      higher peak discharge rates for fast as compared with slow saccades of the same
      amplitude. Moreover, reflecting systematic differences in saccade velocity rather
      than an influence of eye position itself, FOR bursts showed subtle but recurrent
      and, at the population level, statistically significant differences between
      centripetal and centrifugal saccades that closely paralleled the eye position
      dependency of saccadic dysmetria seen after FOR lesions. We conclude that the FOR
      output signal is not, as previously proposed, specifically related to the
      temporal properties of the saccade, but also contains information about saccade
      velocity. Moreover, the FOR output signal appears to change systematically
      depending on the actual kinematic properties of the saccade, in a way that would
      help to maintain saccadic accuracy.

PMID- 14662465
TI  - Neurons in the caudal frontal eye fields of monkeys signal three-dimensional
      tracking.
AB  - To maintain optimal clarity of objects moving in three dimensions, precise
      coordination of binocular eye movements is required in frontal-eyed primates.
      Caudal parts of the frontal eye fields (FEFs) contain smooth pursuit neurons and
      the discharge of the majority of them is related to vergence eye movements as
      well. However, whether or not those pursuit neurons carry true binocular signals
      has not been tested critically. Using dichoptic stimuli that dissociate
      horizontal movements of the left and right eyes, we found that all pursuit
      related, FEF neurons tested carried binocular signals.

PMID- 14662466
TI  - Vestibular signals of posterior parietal cortex neurons during active and passive
      head movements in macaque monkeys.
AB  - The posterior parietal cortex may function as an interface between sensory and
      motor cortices and thus could be involved in the formation of motor plans as well
      as abstract representations of space. We have recorded from neurons in the
      intraparietal sulcus, namely, the ventral and medial intraparietal areas (VIP and
      MIP, respectively), and analyzed their head-movement-related signals in relation
      to passive and active movements. To generate active head movements, we made the
      animals track a moving fixation spot in the horizontal plane under head-free
      conditions. When under certain circumstances the animals were tracking the
      fixation spot almost exclusively via head movements, a clear correlation between
      neuronal firing rate and head movement could be established. Furthermore, a newly
      employed paradigm, the "replay method," made available direct comparison of
      neuronal firing behavior under active and passive movement conditions. In such
      case, the animals were allowed to make spontaneous head movements in darkness.
      Subsequently, the heads were fixed and the previously recorded active head
      movement profile was reproduced by a turntable as passive stimulation. Neuronal
      responses ranged from total extinction of the vestibular signal during active
      movement to presence of activity only during active movement. Furthermore, in
      approximately one-third of the neurons, a change of vestibular on-direction
      depending on active versus passive movement mode was observed, that is, type I
      neurons became type II neurons, etc. We suggest that the role of parietal
      vestibular neurons has to be sought in sensory space representation rather than
      reflex behavior and motor control contexts.

PMID- 14662467
TI  - Inhibitory interhemispheric visuovisual interaction in motion perception.
AB  - Findings of an earlier functional magnetic resonance imaging (fMRI) study that
      coherent motion stimulation of the right or left visual hemifield exhibited
      negative signal changes (deactivations) in the primary visual cortex and the
      lateral geniculate nucleus contralateral to the stimulated hemisphere were
      evaluated to determine the functional significance of this contralateral
      inhibition of the visual system. Fourteen subjects participated in a
      psychophysical study on the perception of single object motion (0.4 degrees /s)
      in one visual hemifield with or without concurrent coherent motion stimulation of
      the contralateral hemifield. Mean detection times for horizontal object motion
      (0.5 +/- 0.19 vs. 0.61 +/- 0.22 s) and vertical object motion (0.53 +/- 0.19 vs.
      0.72 +/- 0.34 s) were significantly prolonged during concurrent motion pattern
      stimulation in the contralateral hemifield. These data support the interpretation
      that the deactivation of neuronal activity in the visual system found by fMRI is
      associated with a functional decrement in the sensitivity needed to perceive
      motion and may reflect transcallosal attentional shifts between the two
      hemispheres.

PMID- 14662468
TI  - Delayed saccades, but not delayed manual aiming movements, require visual
      attention shifts.
AB  - Several studies have shown that during the preparation of a goal-directed
      movement, perceptual selection (i.e., visual attention) and action selection (the
      selection of the movement target) are closely coupled. Here, we study attentional
      selection in situations in which delayed saccadic eye movements and delayed
      manual movements are prepared. A dual-task paradigm was used which combined the
      movement preparation with a perceptual discrimination task. The results
      demonstrate a fundamental difference between the preparation of saccades and of
      manual reaching. For delayed saccades, attention is pinned to the saccade target
      until the onset of the response. This does not hold for manual reaching, however.
      Although fast reaching movements require attention, reaches delayed more than 300
      ms after movement cue onset can be already performed "off-line"; that is,
      attention can be withdrawn from the movement target.

PMID- 14662469
TI  - Prolonged optokinetic stimulation generates podokinetic after rotation.
AB  - Previous studies showed that after prolonged stepping in place on the center of a
      rotating platform blindfolded subjects could no longer step in place on a firm
      floor. Instead, they invariably rotated themselves relative to space without
      perceiving their rotation, a phenomenon termed podokinetic after-rotation (PKAR).
      We speculated that prolonged optokinetic stimulation (OK) alone may generate
      similar PKAR. The purpose of this study was to evaluate the effects of prolonged
      OK on podokinetic (PK) responses. Ten healthy subjects participated in the study.
      After a control stepping test, they were seated in a circular closed cage and
      randomly (right or left) exposed to an OK (45 degrees /s) covering the whole
      visual field for 30 min. After this procedure, blindfolded subjects attempted to
      step in place on the stationary floor for 30 min. When trying to do so, all
      subjects turned relative to space without any perception of rotation. The
      direction of this optokinetically after-rotation (oPKAR) was opposite of that of
      the direction of OK. Mean peak velocity of oPKAR was 7.8 +/- 4.1 degrees /s, and
      it was reached after approximately 6 min of stepping. After that, there was a
      progressive velocity decay, which exhibited a discharging time constant on the
      order of 42 min toward a final positive asymptote of 3.1 degrees /s. We conclude
      that OK alone causes oPKAR. Long-term OK probably charges a storage element for
      podomotor activity with a relatively prolonged time constant. This novel form of
      neural interaction and adaptive plasticity may have significant implications for
      the treatment of vestibular and parietal lobe disorders.

PMID- 14662470
TI  - A modeling approach to the human spatial orientation system.
AB  - The human spatial orientation system is highly complex and nonlinear. It is
      difficult, therefore, to arrive at an unequivocal model of the underlying
      processing by merely combining the known elementary mechanisms ("bottom-up"
      approach); additional "top-down" concepts are required to narrow the choice
      between several formally equivalent solutions. We here suggest a concept in which
      sensorimotor control is based on a meta-level that provides an internal
      representation of the physical stimuli acting upon a subject (e.g., tilt of the
      support surface), whereas the classic reflex concept essentially proceeds from a
      direct coupling between physiological stimuli, sensors and actuators. At the
      hypothesized meta-level, the axial body segments are represented as a stack of
      superimposed platforms with the lowermost platform (generally the feet) riding on
      a support surface that acts as the buttress for the subject's active movements.
      From the sensory point of view, this stack constitutes a system of nested
      references. This concept explains data from various experiments dealing with self
      and object motion perception and body stabilization in a more exhaustive way
      than does the classic concept. In our view, it provides a robust, flexible, and
      modular framework for perception and action in space.

PMID- 14662471
TI  - Spatial memory deficits in patients with chronic bilateral vestibular failure.
AB  - The role of the vestibular system for navigation and spatial memory has been
      demonstrated in animals but not in humans. Vestibular signals are necessary for
      location-specific "place cell" activity in the hippocampus which provides a
      putative neural substrate for the spatial representation involved in navigation.
      To investigate the spatial memory in patients with bilateral vestibular failure
      due to NF2 with bilateral neurectomy, a virtual variant (on a PC) of the Morris
      water task adapted to humans was used. Significant spatial learning and memory
      deficits were shown in 12 patients as compared to 10 healthy controls. These data
      suggest that functional hippocampal deficits manifest due to a chronic lack of
      vestibular input in these patients. These deficits can even be demonstrated with
      the subjects stationary, i.e., without any actual vestibular or somatosensory
      stimulation.

PMID- 14662472
TI  - The human horizontal vestibulo-ocular reflex in response to active and passive
      head impulses after unilateral vestibular deafferentation.
AB  - We studied the compensatory eye movements made by subjects with unilateral
      vestibular deficits in response to passive (unpredictable, manually generated)
      and active (predictable, self-generated) head impulses. A typical head impulse is
      a brief, low-amplitude (15-20 degrees ), high-velocity (150-350 degrees /s), high
      acceleration (4000-6000 degrees /s(2)), yaw head-on-trunk rotation. In the
      initial 75 ms of the response, the vestibulo-ocular reflex gain was significantly
      higher during active head impulses to both ipsilesional and contralesional sides,
      than during passive impulses. Mean gains were 0.15 (ipsilesional passive), 0.44
      (ipsilesional active), 0.5 (contralesional passive), and 0.76 (contralesional
      active). Differences between active and passive head impulses were present from
      near the onset of head rotation. The mechanism for producing this behavior is
      unclear, but the findings could be related to enhanced sensitivity of second
      order neurons during active head impulses. However, even with active movements,
      there is still a large and statistically significant asymmetry in the eye
      movement responses for ipsilesional as opposed to contralesional head rotations.
      After 75 ms, rapid corrective eye movements often were generated to reduce any
      remaining gaze error.

PMID- 14662473
TI  - Evaluating small eye movements in patients with saccadic palsies.
AB  - Slow saccades are an important diagnostic feature of a range of degenerative,
      metabolic, and genetic diseases of the nervous system. Many affected patients
      have difficulty initiating saccades, and the movements themselves may be small,
      making it difficult to make comparisons with control subjects. A large-field
      optokinetic stimulus may elicit quick phases of nystagmus in patients who cannot
      initiate voluntary saccades, but these movements may also be small. We show that
      it is still possible to compare amplitude-duration and amplitude-peak velocity
      relations with controls if data are fit with a power function (rather than an
      exponential equation). When analyzed this way, the dynamic properties of small
      saccades and quick phases from patients with progressive supranuclear palsy (PSP)
      could be differentiated from fast movements made by patients with idiopathic
      Parkinson's disease or controls. Normal saccades show a fairly constant ratio:
      peak velocity/mean velocity (Q approximately 1.6 for vertical saccades). This
      ratio was abnormally high (Q >3) for some larger saccades made by patients with
      PSP, suggesting that either these movements were not entirely saccadic or that
      they were composed of a series of small saccades.

PMID- 14662474
TI  - Incomitance of ocular rotation axes in trochlear nerve palsy.
AB  - Strabismus due to palsy of a single muscle in one eye is always incomitant, which
      is a consequence of Hering's law of equal innervation. We asked whether this law
      had similar consequences on the orientation of ocular rotation axes. Patients
      with unilateral trochlear nerve palsy were oscillated about the nasooccipital (=
      roll) axis (+/-35 degrees, 0.3 Hz), and monocularly fixed on targets on a head
      fixed Hess screen. Both the covered and uncovered eyes were measured with dual
      search coils. The rotation axis of the covered eye (paretic or healthy) tilted
      more nasally from the line of sight when gaze was directed toward the side of the
      healthy eye. The rotation axis of the viewing eye (paretic or healthy), however,
      remained roughly aligned with the line of sight. We conclude that incomitance due
      to eye muscle palsy extends to ocular rotation axes during vestibular
      stimulation.

PMID- 14662475
TI  - Eye movements and balance.

PMID- 14662476
TI  - The critical role of velocity storage in production of motion sickness.
AB  - We propose that motion sickness is mediated through the orientation properties of
      velocity storage in the vestibular system that tend to align eye velocity
      produced by the angular vestibulo-ocular reflex (aVOR) with gravito-inertial
      acceleration (GIA). (GIA is the sum of the linear accelerations acting on the
      head. In the absence of translational accelerations, gravity is the GIA.) We
      further postulate that motion sickness produced by cross-coupled vestibular
      stimulation can be characterized by a metric composed of the disparity between
      the axis of eye rotation and the GIA, the strength of the response to angular
      motion, and the response duration, as determined by the central vestibular time
      constant, that is, by the time constant of velocity storage. The nodulus and
      uvula of the vestibulocerebellum are likely to be the central sites where the
      disparity is sensed, where the vestibular time constants are habituated, and
      where links are made to the autonomic system to produce the symptoms and signs.

PMID- 14662500
TI  - Torsional eye movement responses to monaural and binaural galvanic vestibular
      stimulation: side-to-side asymmetries.
AB  - Vestibular stimulation by head accelerations always involves multisensory
      activation of the vestibular, somatosensory, and visual systems. Over the past
      few years, galvanic vestibular stimulation (GVS) has become increasingly popular
      for testing vestibular function for clinical and research purposes. Although GVS
      provides a nonphysiological stimulation, it is more selective than natural head
      accelerations and is thus an attractive tool for such tests. Eye movement
      responses elicited by GVS mainly consist of torsional and horizontal components,
      as first described by Hitzig in 1871. Animal experiments have shown that GVS
      increases the vestibular afferent spike frequency at the cathodal site and
      decreases it at the anodal site of stimulation. As a continuation of a study on
      age-dependency of eye movement responses to GVS, we analyzed side-to-side
      asymmetries in healthy subjects. It is necessary to know the normal range of
      asymmetry between left- and right-sided stimulation to interpret GVS responses in
      patients with vestibular diseases.

PMID- 14662504
TI  - Nonlinear nystagmus processing causes torsional VOR nonlinearity.
AB  - The eye movement component that rotates around the line of sight, i.e., the
      ocular torsion, is in many aspects different from horizontal and vertical eye
      movements. While ocular torsion is mediated only by reflexive pathways like the
      torsional vestibulo-ocular and optokinetic reflexes (TVOR and OKN, respectively),
      horizontal and vertical components are also subject to intentional control
      mechanisms that are mediated by the saccadic and the pursuit systems. Dynamic
      properties of torsional eye movements are also very distinct. While horizontal
      and vertical VOR components show a gain close to unity and a small neural
      integration leakage with a time constant around pi=30 s, the TVOR shows a smaller
      gain of 0.4 and also a greater leakage with pi=2 s. During slow head rotations in
      roll, the TVOR is even less compensatory. At small stimulation levels the gain
      drops to a value of 0.2 and proves thus to be nonlinear, i.e., to depend on the
      stimulus magnitude. In a recent study, we hypothesized that this nonlinearity
      might be the result of a nonlinear processing of nystagmus quick phases rather
      than a nonlinearity in direct or integrator TVOR pathways. In the present study,
      we experimentally tested this hypothesis by measuring ocular torsion responses at
      different head rotation speeds. In addition to the conventional approach of
      analyzing slow-phase velocity (SPV) gains, we also analyzed properties of
      nystagmus quick phases. This method proved to be suitable for determining whether
      nonlinear processing of nystagmus frequency is responsible for the TVOR
      nonlinearity.

PMID- 14662507
TI  - Common reference system for estimation of the postural and subjective visual
      vertical.
AB  - When tilted subjects are asked to set a luminous line to the perceived earth
      vertical in a dark surrounding, they systematically underestimate the true
      direction of earth-vertical at large tilt angles, a phenomenon first described by
      Aubert (A-phenomenon). At small tilt angles, subjects usually overestimate the
      direction of earth-vertical. Overestimation has been first reported by Muller,
      who termed the notion of E-phenomenon. Since these first reports, this rather
      remarkable error behavior has been studied extensively. The prevailing notion in
      most earlier studies was that the erroneous estimation of verticality results
      from otolith signals, which are thought to represent the major input for spatial
      orientation, and their interaction with somatosensory signals. To bring the
      subjects into tilted positions, most investigators used slow tilt velocities or
      waited for some time to prevent interaction with semicircular canal activity.
      Here, we tested the hypothesis that vestibular cues about self-orientation
      relative to gravity are most reliable when both the semicircular canals and the
      otolith organs are optimally activated. To compare the error behavior in
      estimations of the visual vertical and perceived body position, we used self
      controlled passive tilts at constant velocity or acceleration.

PMID- 14662511
TI  - Haptic subjective vertical shows context dependence: task and vision play a role
      during dynamic tilt stimulation.
AB  - Perceiving one's vertical is an integral part of efficiently functioning in an
      environment physically polarized along that dimension. How one determines the
      direction of gravity is not a task left only to inertial sensors, such as the
      vestibular organs, rather as numerous studies have shown, this task is influenced
      visually and somatosensorily. In addition, there is evidence that higher order
      cognitive effects such as expectancies and context are critical in perception of
      the vertical. One's ability to integrate these various inputs during normal
      activity is not generally questioned, one's doubts being satisfied by observing a
      waiter navigating a crowded restaurant with a tray balanced on one hand, neither
      tripping or dropping an entree. But how these various sources are integrated is
      still debated. Most research focuses on subjective vertical perception used
      visual matching/alignment tasks, verbal reports, or saccadic eye movements as a
      dependent measure. Although a motor task involving a joystick or indicator to be
      aligned with gravity without visual feedback is used much less frequently, there
      is good evidence that individuals easily orient limbs to an external gravity
      aligned coordinate axis while being statically tilted. By exposure to a dynamic
      situation, the central nervous system should be no more challenged by the task of
      determining the subjective vertical than during static conditions, because our
      spatial orientation systems were likely selected for just that. In addition, the
      sensitive calibration between visual and other sensory input also must have been
      key to its selection. This sensory interaction can be tested by changing the
      relation between the various sources. With the advent of virtual reality
      technology, a complex and "natural" visual stimulus is achievable and is easily
      manipulable. How one tests perception of verticality is also a pertinent question
      when researching spatial orientation systems. The system's performance may be
      better indicated by a task of higher relevance to its normal function. In other
      words, the dependent measure can be made more or less relevant to real-world
      tasks. With an experimental design that attempts to mimic natural conditions, the
      current study focuses on two main topics. First, how does manipulation of the
      visual inputs during passive roll-tilt affect one's sense of body orientation?
      And second, how does changing the task used to measure subjective vertical affect
      one's performance?

PMID- 14662512
TI  - Proton leak and hydrogen peroxide production in liver mitochondria from energy
      restricted rats.
AB  - Energy restriction (ER), without malnutrition, is the only environmental
      intervention that consistently increases maximum life span in laboratory rodents.
      One theory proposes that a reduction in energy expenditure and reactive oxygen
      species production is the mechanism responsible for this action of ER. To further
      test this theory, proton leak, H2O2 production, lipid peroxidation, and protein
      carbonyls were measured in mitochondria from FBNF1 rats fed either a control or
      40% ER diet (onset at 6 mo of age). Liver mitochondria were isolated at 7 and 12
      mo of age. Liver weight decreased 25 and 36% at 1 and 6 mo of ER, respectively (P
      < 0.05). ER resulted in an increase (P < 0.05) in percent total polyunsaturates,
      n-6 polyunsaturates, and total unsaturates (6 mo only) in mitochondrial lipids.
      These changes, however, were not associated with significant alterations in
      mitochondrial function. State 4 respiration and membrane potential were not
      different (P > 0.05) between groups at either assessment period. Similarly,
      proton leak kinetics were not different between control and ER animals. Top-down
      metabolic control analysis and its extension, elasticity analysis, were used at
      the 6-mo assessment and revealed no difference in control of the oxidative
      phosphorylation system between control and ER rats. H2O2 production with either
      succinate or pyruvate/malate substrates was also not different (P > 0.05) between
      groups at either time point. In conclusion, ER did not alter proton leak or H2O2
      production at this age or stage of restriction in liver.

PMID- 14662513
TI  - Endurance training partially reverses dietary-induced leptin resistance in rodent
      skeletal muscle.
AB  - Leptin acutely stimulates skeletal muscle fatty acid (FA) metabolism in lean
      rodents and humans. This stimulatory effect is eliminated following the feeding
      of high-fat diets in rodents as well as in obese humans. The mechanism(s)
      responsible for the development of skeletal muscle leptin resistance is unknown;
      however, a role for increased suppressor of cytokine signaling-3 (SOCS3)
      inhibition of the leptin receptor has been demonstrated in other rodent tissues.
      Furthermore, whether exercise intervention is an effective strategy to prevent or
      attenuate the development of skeletal muscle leptin resistance has not been
      investigated. Toward this end, 48 Sprague-Dawley rats (175-190 g; approximately 2
      3 mo of age) were fed control or high-fat (60% kcal) diets for 4 wk and either
      remained sedentary or were treadmill trained. In control diet-fed animals that
      remained sedentary (CS) or were endurance trained (CT), leptin stimulated FA
      oxidation (CS +32 +/- 15%, CT +30 +/- 17%; P < 0.05), suppressed triacylglycerol
      (TAG) esterification (CS -17 +/- 7%, CT -24 +/- 8%; P < 0.05), and reduced the
      esterification-to-oxidation ratio (CS -19 +/- 13%, CT -29 +/- 10%; P < 0.001) in
      soleus muscle. High-fat feeding induced leptin resistance in the soleus of
      sedentary rats (FS), whereas endurance exercise training (FT) restored the
      ability of leptin to suppress TAG esterification (-19 +/- 9%, P = 0.038).
      Training did not completely restore the ability of leptin to stimulate FA
      oxidation. High-fat diets stimulated SOCS3 mRNA expression irrespective of
      training status (FS +451 +/- 120%, P = 0.024; FT +381 +/- 141%, P = 0.023). Thus
      the development of skeletal muscle leptin resistance appears to involve an
      increase in SOCS3 mRNA expression. Endurance training was generally effective in
      preventing the development of leptin resistance, although this did not appear to
      require a decrease in SOCS3 expression. Future studies should examine changes in
      the actual protein content of SOCS3 in muscle and establish whether aerobic
      exercise is also effective in treating leptin resistance in humans.

PMID- 14662514
TI  - Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow
      cytometric study.
AB  - Multiple sclerosis is thought to be an autoimmune, inflammatory, cell-mediated
      disease. However, there is evidence suggesting that autoantibodies could play a
      role in the pathogenesis of multiple sclerosis. Many studies have looked for
      antibodies to candidate antigens such as myelin basic protein or myelin
      oligodendrocyte glycoprotein, with inconclusive results. In order to determine
      whether antibodies to cell surface determinants on oligodendrocyte or neuronal
      cells were present in multiple sclerosis, we used flow cytometry to detect
      antibody binding to intact cultured human cell lines, comparing sera from
      multiple sclerosis patients with sera from patients with other inflammatory CNS
      diseases. Sera from healthy individuals were used to determine a normal range.
      Significant surface binding of IgG or IgM antibodies to oligodendrocyte precursor
      (OPC)-derived cell lines was seen in 50% of multiple sclerosis sera with no
      significant difference between secondary progressive (SPMS) and relapsing
      remitting (RRMS) subgroups. In contrast, binding to a neuronal cell line, SK-N
      SH, was seen with 70% of SPMS sera compared with 25% of RRMS sera (P < 0.001). No
      significant difference in antibody binding between multiple sclerosis sera and
      control sera was seen when OPCs were differentiated or when the cells were
      permeabilized to expose intracellular antigens. Results from all nine patients
      with 'benign' multiple sclerosis were indistinguishable from controls. This study
      represents a systematic approach to begin to define new antigenic targets in
      multiple sclerosis and demonstrates that antibodies to accessible antigens on the
      cell surface of both OPCs and neurons are present in some patients. The results
      lend support to the possibility that autoantibody-mediated processes are
      important in a subgroup of multiple sclerosis patients. Identification of the
      cell surface determinants to which the antibodies bind may shed light on new
      targets for therapeutic intervention.

PMID- 14662515
TI  - Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at
      sites of axonal injury in the spinal cord in EAE.
AB  - Axonal degeneration contributes to the development of non-remitting neurological
      deficits and disability in multiple sclerosis, but the molecular mechanisms that
      underlie axonal loss in multiple sclerosis are not clearly understood. Studies of
      white matter axonal injury have demonstrated that voltage-gated sodium channels
      can provide a route for sodium influx into axons that triggers reverse operation
      of the Na(+)/Ca(2+) exchanger (NCX) and subsequent influx of damaging levels of
      intra-axonal calcium. The molecular identities of the involved sodium channels
      have, however, not been determined. We have previously demonstrated extensive
      regions of diffuse expression of Na(v)1.6 and Na(v)1.2 sodium channels along
      demyelinated axons in experimental allergic encephalomyelitis (EAE). Based on the
      hypothesis that the co-localization of Na(v)1.6 and NCX along extensive regions
      of demyelinated axons may predispose these axons to injury, we examined the
      expression of myelin basic protein, Na(v)1.2, Na(v)1.6, NCX and beta-amyloid
      precursor protein (beta-APP), a marker of axonal injury, in the spinal cord
      dorsal columns of mice with EAE. We demonstrate a significant increase in the
      number of demyelinated axons demonstrating diffuse Na(v)1.6 and Na(v)1.2 sodium
      channel immunoreactivity in EAE (92.2 +/- 2.1% of beta-APP positive axons were
      Na(v)1.6-positive). Only 38.0 +/- 2.9% of beta-APP positive axons were Na(v)1.2
      positive, and 95% of these co-expressed Na(v)1.6 together with Na(v)1.2. Using
      triple-labelled fluorescent immunohistochemistry, we demonstrate that 73.5 +/-
      4.3% of beta-APP positive axons co-express Na(v)1.6 and NCX, compared with 4.4 +/
      1.0% in beta-APP negative axons. Our results indicate that co-expression of
      Na(v)1.6 and NCX is associated with axonal injury in the spinal cord in EAE.

PMID- 14662516
TI  - Out-of-body experience and autoscopy of neurological origin.
AB  - During an out-of-body experience (OBE), the experient seems to be awake and to
      see his body and the world from a location outside the physical body. A closely
      related experience is autoscopy (AS), which is characterized by the experience of
      seeing one's body in extrapersonal space. Yet, despite great public interest and
      many case studies, systematic neurological studies of OBE and AS are extremely
      rare and, to date, no testable neuroscientific theory exists. The present study
      describes phenomenological, neuropsychological and neuroimaging correlates of OBE
      and AS in six neurological patients. We provide neurological evidence that both
      experiences share important central mechanisms. We show that OBE and AS are
      frequently associated with pathological sensations of position, movement and
      perceived completeness of one's own body. These include vestibular sensations
      (such as floating, flying, elevation and rotation), visual body-part illusions
      (such as the illusory shortening, transformation or movement of an extremity) and
      the experience of seeing one's body only partially during an OBE or AS. We also
      find that the patient's body position prior to the experience influences OBE and
      AS. Finally, in five patients, brain damage or brain dysfunction is localized to
      the temporo-parietal junction (TPJ). These results suggest that the complex
      experiences of OBE and AS represent paroxysmal disorders of body perception and
      cognition (or body schema). The processes of body perception and cognition, and
      the unconscious creation of central representation(s) of one's own body based on
      proprioceptive, tactile, visual and vestibular information-as well as their
      integration with sensory information of extrapersonal space-is a prerequisite for
      rapid and effective action with our surroundings. Based on our findings, we
      speculate that ambiguous input from these different sensory systems is an
      important mechanism of OBE and AS, and thus the intriguing experience of seeing
      one's body in a position that does not coincide with its felt position. We
      suggest that OBE and AS are related to a failure to integrate proprioceptive,
      tactile and visual information with respect to one's own body (disintegration in
      personal space) and by a vestibular dysfunction leading to an additional
      disintegration between personal (vestibular) space and extrapersonal (visual)
      space. We argue that both disintegrations (personal; personal-extrapersonal) are
      necessary for the occurrence of OBE and AS, and that they are due to a paroxysmal
      cerebral dysfunction of the TPJ in a state of partially and briefly impaired
      consciousness.

PMID- 14662517
TI  - Abnormal cortex-muscle interactions in subjects with X-linked Kallmann's syndrome
      and mirror movements.
AB  - X-linked Kallmann's (XKS) subjects, who display mirror movements, have abnormal
      corticospinal tracts which innervate motoneurons of the left and right distal
      muscles of the upper limb. The size of the abnormal ipsilateral projection is
      variable. We have used coherence and cumulant analysis between EEG and first
      dorsal interosseous muscle (1DI) EMG to explore mechanisms underlying mirror
      movements in three XKS subjects. Results are compared with those of three normal
      subjects. We argue that significant coherence is functionally relevant when
      associated with a negative cumulant at an appropriate lag. Given this, normal
      subjects showed coherence at approximately 22 Hz between the EEG recorded over
      the sensori-motor cortex contralateral to the voluntarily moved hand and the 1DI
      EMG of this hand. No significant coherence was seen between 1DI EMG and the
      sensori-motor cortex ipsilateral to the muscle activity. In contrast, two of the
      XKS subjects (K2 and K4) had significant coherence at 22 Hz, together with a
      negative cumulant at an appropriate lag, between the ipsilateral cortical EEG and
      the 1DI EMG of the voluntarily activated hand. This implies that activity in the
      abnormal ipsilateral corticospinal projection can contribute to the voluntary
      drive. For these two subjects, the ipsilateral corticospinal projection was
      greater than the contralateral projection, as revealed using magnetic brain
      stimulation. In one of these subjects, K4, significant 22 Hz coherence and
      negative cumulant was also seen between the EMG of the voluntarily activated hand
      and the cortex contralateral to this hand. In the third subject, K4a, coherence
      and negative cumulant was detected between the EMG of the voluntary side and the
      cortical activity contralateral to this hand. The contralateral cortico spinal
      projection of this subject was greater than the ipsilateral projection. Regarding
      the mirroring hand of the XKS subjects, coherence (with negative cumulant at an
      appropriate lag) was seen in all three subjects between the EMG recorded from the
      mirroring hand and cortical EEG ipsilateral to this hand. This provides evidence
      that activity in the aberrant ipsilateral projection is involved in producing the
      drive that results in mirror movements. In one subject, K4, coherence and
      negative cumulant was also seen between the EMG of the mirroring hand and motor
      cortical activity contralateral to this hand. Thus, in this subject, activity in
      the corticospinal projection contralateral to the mirroring hand also contributed
      to the mirror movements. In conclusion, this study has provided further evidence
      that the 22 Hz coherence seen between EEG and EMG is dependent upon corticospinal
      activity and has furthered our understanding of mechanisms underlying mirror
      movements.

PMID- 14662518
TI  - Anti-HIV drugs decrease the expression of matrix metalloproteinases in astrocytes
      and microglia.
AB  - The introduction of potent antiretroviral drugs for the treatment of patients
      with human immunodeficiency virus (HIV) infection has dramatically reduced the
      prevalence of HIV-associated neurological disorders. Such diseases can be
      mediated by proteolytic enzymes, i.e. matrix metalloproteinases (MMPs) and, in
      particular gelatinases, released from glial cells. The aim of this study was to
      investigate whether the antiretroviral drugs commonly used for the treatment of
      HIV-infected patients modulate the activity of MMPs in astrocyte and microglial
      cultures. Primary cultures of rat astrocyte and microglia were treated with
      different doses of zidovudine (AZT) or indinavir (IDV) for 20 h and
      simultaneously activated by exposure to lipopolysaccharide (LPS). Culture
      supernatants collected from astrocytes and microglia after 24 h incubation were
      subjected to gelatin zymography and western blot analysis for the assessment of
      MMP-2 (gelatinase A) and MMP-9 (gelatinase B) protein levels. Total RNA was
      extracted from glial cells and used for reverse transcriptase-polymerase chain
      reaction for the assessment of mRNA expression. Our results indicate that both
      astrocyte and microglial cells constitutively express MMP-2 mRNA and protein. LPS
      treatment increased MMP-2 mRNA and protein expression in astrocytes, but not in
      microglial cells. The treatment with both AZT and IDV dose-dependently inhibited
      the expression of MMP-2 in astrocytes, whereas it had no effect on microglial
      cells. The expression of MMP-9 in both astrocytes and microglia was induced by
      LPS treatment and was dose-dependently inhibited by AZT and IDV treatment in LPS
      stimulated astrocytes and microglia. These results raise the possibility that AZT
      and IDV interfere directly with MMP production in glial cells and independently
      from their antiviral activity, thus suggesting the possible therapeutical use in
      neurological diseases associated with MMPs involvement.

PMID- 14662519
TI  - The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's
      disease.
AB  - Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to
      cause early-onset, autosomal recessive Parkinson's disease. As no information is
      available regarding the distribution of DJ-1 protein in the human brain, in this
      study we used a monoclonal antibody for DJ-1 to map its distribution in frontal
      cortex and substantia nigra, regions invariably involved in Parkinson's disease.
      Western blotting of human frontal cortex showed DJ-1 to be an abundant protein in
      control, idiopathic Parkinson's disease, cases with clinical and pathological
      phenotypes of Parkinson's disease with R98Q polymorphism for DJ-1, and in
      progressive supranuclear palsy (PSP) brains. We also showed that DJ-1
      immunoreactivity (IR) was particularly prominent in astrocytes and astrocytic
      processes in both control and Parkinson's disease frontal cortex, whereas neurons
      showed light or no DJ-1 IR. Only occasional Lewy bodies (LBs), the pathological
      hallmarks of Parkinson's disease, showed faint DJ-1 IR, localized to the outer
      halo. In preclinical studies we showed that DJ-1 is expressed in primary
      hippocampal and astrocyte cultures of mouse brain. By 2D gel analysis we also
      showed multiple pI isoforms for DJ-1 ranging between 5.5-6.6 in both control and
      Parkinson's disease brains, whilst exposure of M17 cells to the oxidizing agent
      paraquat was manifested as a shift in pI of endogenous DJ-1 towards more acidic
      isoforms. We conclude that DJ-1 is not an essential component of LBs and Lewy
      neurites, is expressed mainly by astrocytes in human brain tissue and is
      sensitive to oxidative stress conditions. These results are consistent with the
      hypothesis that neuronal-glial interactions are important in the pathophysiology
      of Parkinson's disease.

PMID- 14662520
TI  - Effects of deep brain stimulation and medication on bradykinesia and muscle
      activation in Parkinson's disease.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and
      antiparkinsonian medication (Meds) have proved to be effective therapies for
      treating bradykinesia in Parkinson's disease. However, it is not currently known
      how or to what extent STN stimulation alters the control signals to agonist and
      antagonist muscles to change movement speed. Our objective was to investigate
      movement speed along with the amplitude and temporal features of EMG activity to
      determine how and to what extent these parameters are changed by DBS and
      medication. Nine patients with Parkinson's disease were studied following
      neurosurgery that implanted high-frequency stimulating electrodes in the STN. The
      experiments for the patients were performed in each of four treatment conditions:
      (i) OFF treatment; (ii) STN DBS; (iii) Meds; and (iv) Meds plus STN DBS. Also, a
      group of age- and gender-matched control subjects were examined. Medication and
      DBS had similar effects in that both treatments increased movement speed,
      increased the amplitude of the first agonist burst, increased burst duration,
      reduced the number of agonist bursts, reduced cocontraction, increased the size
      of the antagonist EMG, and reduced the centroid time of the antagonist EMG. When
      DBS and medication were combined, only temporal measures of burst duration and
      the number of agonist bursts were different from the medication alone condition.
      There was a positive association between the level of bradykinesia OFF treatment
      and the level of bradykinesia following DBS and medication. The movement speed of
      neurologically normal control subjects' was over 40% higher during both flexion
      and extension movements when compared with the patients during Meds plus STN DBS.
      The changes in the muscle activation patterns provide a mechanism of action for
      the pharmacological and surgical interventions used to treat bradykinesia in
      Parkinson's disease. However, despite the success of medication and DBS at
      improving bradykinesia in patients with Parkinson's disease, patients' movement
      speed was not restored to normal due to limitations in the amplitude and temporal
      scaling of the agonist and antagonist bursting pattern. These findings suggest a
      link between basal ganglia function in scaling both the amplitude and temporal
      parameters of the input to the motor neuron pool.

PMID- 14662521
TI  - Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a
      Huntington's mouse model.
AB  - Symptoms of Huntington's disease may be caused by a toxic insult triggered by the
      mutant human huntingtin (Htt) protein itself, by a maladaptive protective
      mechanism initiated in response to an insult, or by a combination of these. We
      observed a protection from N-methyl-d-aspartate (NMDA) receptor-induced
      excitotoxicity in striata of symptomatic N171-82Q mice, a new transgenic model of
      Huntington's disease. The goal of this study was to determine if NMDA receptor
      mediated signalling pathways are altered in these mice. Multiple proteins of NMDA
      receptor and dopamine D1 receptor pathways are being regulated in ways predictive
      of the protection we observe. Although examining NMDA receptor subunit proteins
      showed no change in NR1, NR2A, or NR2B in the striata of the symptomatic mice, we
      observed a decrease in phosphorylation of NR1 at Ser897, previously reported to
      decrease NMDA receptor current. The dopamine D1 receptor, responsible for protein
      kinase A activation and subsequent phosphorylation of Ser897 of NR1, also showed
      an age-related decrease. Other proteins regulated in this disease were associated
      with PSD-95-like scaffolding proteins of the NMDA receptor. Specifically, we
      observed a decrease in membrane-associated neuronal nitric oxide synthase (nNOS),
      a decrease in PSD-95-like proteins, which link nNOS to the NMDA receptor complex,
      and a decrease in citron, a protein associated with dendritic spine formation.
      From these data, we conclude that the N171-82Q mice seem to be regulating, in a
      protective direction, many of the known effector pathways of NMDA receptor
      induced excitotoxicity. These regulations, although seemingly effective in
      decreasing neuronal death, may in fact be causing some of the symptoms associated
      with the disease.

PMID- 14662522
TI  - Autopsy after termination of pregnancy for fetal anomaly: retrospective cohort
      study.
AB  - OBJECTIVE: To study trends in termination of pregnancy for fetal anomaly over 10
      years and to assess the contribution of autopsy to the final diagnosis and
      counselling after termination. DESIGN: Retrospective study with cases from a
      congenital anomaly register and a defined unselected population. DATA SOURCES:
      Pregnancies resulting in termination for fetal anomaly identified from the Oxford
      congenital anomaly register. Details about the prenatal diagnosis and autopsy
      findings were retrieved from case notes. RESULTS: Of the 57 258 deliveries, 309
      (0.5%) were terminated because of prenatally diagnosed abnormality. There were
      129/29 086 (0.4%) terminations for fetal anomaly carried out in 1991-5 and 180/28
      172 (0.6%) in 1996-2000. The percentage of fetuses that underwent autopsy fell
      from 84% to 67%. Autopsy was performed in 132 cases identified by ultrasound
      scan, with no evidence for abnormal karyotype. In 95 (72%) the autopsy confirmed
      the suspected diagnosis and did not add important further information, two cases
      were not classified, and in 35 (27%) the autopsy added information that led to a
      refinement of the risk of recurrence (reduced in 17, increased in 18); in 11 of
      these 18 cases it was increased to a one in four risk. CONCLUSIONS: Though there
      has been an increase in the rate of terminations of pregnancy for fetal anomaly,
      there has been a decline in the autopsy rate. When a prenatal diagnosis was based
      on the results of a scan only, the addition of information from an autopsy by a
      specialist paediatric pathologist provided important information that changed the
      estimated risk of recurrence in 27% of cases and in 8% this was to a higher (one
      in four) risk.

PMID- 14662523
TI  - Is there a familial link between Down's syndrome and neural tube defects?
      Population and familial survey.
AB  - OBJECTIVE: To verify whether Down's syndrome and neural tube defects arise more
      often in the same family than expected by chance. DESIGN: Population and familial
      survey. SETTING: Network of maternity hospitals in the Latin American
      collaborative study of congenital malformations (ECLAMC) in Argentina, Bolivia,
      Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Uruguay, and Venezuela between
      1982 and 2000. PROBANDS: 2421 cases of neural tube defects, 952 of hydrocephalus,
      and 3095 of Down's syndrome registered from a total of 1 583 838 live births and
      stillbirths. MAIN OUTCOME MEASURES: Observed number of cases of Down's syndrome
      among siblings of probands with a neural tube defect or hydrocephalus and number
      expected on the basis of maternal age; observed number of cases of neural tube
      defects or hydrocephalus among siblings of probands with Down's syndrome and
      number expected according to the prevalence in the same population. RESULTS: Five
      cases of Down's syndrome occurred among 5404 pregnancies previous to a case of
      neural tube defect or hydrocephalus, compared with 5.13 expected after adjustment
      by maternal age. Twelve cases of neural tube defect or hydrocephalus occurred
      among 8066 pregnancies previous to a case of Down's syndrome, compared with 17.18
      expected on the basis of the birth prevalence for neural tube defects plus
      hydrocephalus in the same population. CONCLUSION: No association occurred between
      families at risk of neural tube defects and those at risk of Down's syndrome.

PMID- 14662524
TI  - The University of Michigan.

PMID- 14662526
TI  - Frequency of burn-trauma patients in an urban setting.
AB  - BACKGROUND: Burn-trauma patient encounters constitute 5% of the emergency
      department population. HYPOTHESIS: A large urban hospital will treat twice as
      many (ie, 10%) burn-trauma patients. DESIGN: Retrospective 44-month study.
      SETTING: Metropolitan county hospital. PATIENTS: Population-based sample of burn
      only (n = 1102), burn-trauma (n = 120), and assault burn-trauma (n = 43)
      patients. MAIN OUTCOME MEASURES: Frequency and demographics. RESULTS: Just under
      10% (n = 120) of the burn population had burn-trauma injuries. The mean +/- SD
      Injury Severity Score was 12 +/- 12 in these burn-trauma patients: 4 +/- 2 in
      outpatients and 14 +/- 13 in inpatients. The burn-only and burn-trauma groups had
      similar age ranges, ethnic distribution, frequency of inhalation injury,
      substance abuse, malnutrition, sepsis, pneumonia, diabetes mellitus, percentage
      total burn surface area, number of procedures, grafted areas, and mortality.
      Forty-three burn-trauma patients (35.8%) sustained injuries due to assault,
      compared with 123 (11.2%) in the burn-only group (P<.001). Burn-trauma patients
      who were assaulted had a mean +/- SD Injury Severity Score of 11 +/- 10. There
      was a significantly increased male-female ratio among the assault burn-trauma
      patients (6:1) compared with the burn-trauma (3:1) and burn-only (2.3:1) groups
      (P<.04). Most of these injuries were caused by an unknown assailant, in
      connection with an automobile, a motorcycle, a bicycle, or pedestrians
      intentionally struck by moving vehicles, or by child abuse. The main mechanism of
      injury was contact in 57 burn-trauma patients (47.5%), compared with 127 (11.5%)
      in the burn-only group (P<.001). CONCLUSIONS: A large urban population will have
      an increased frequency (2-fold in our center) of burn-trauma injuries. Assault
      and child abuse are significant contributory factors to burn-trauma injuries in
      this population.

PMID- 14662525
TI  - Reversible cardiac sympathectomy by high thoracic epidural anesthesia improves
      regional left ventricular function in patients undergoing coronary artery bypass
      grafting: a randomized trial.
AB  - HYPOTHESIS: To evaluate the effects of high thoracic epidural anesthesia (TEA) on
      global and regional myocardial function and on perioperative coronary risk in
      patients undergoing coronary artery bypass grafting. DESIGN, SETTING, AND
      PATIENTS: Prospective and randomized clinical trial blinded for the primary
      outcome measure of 73 patients scheduled for coronary artery bypass grafting who
      had a left ventricular ejection fraction of 50% or more conducted from February
      1, 2000, through August 31, 2000, at University Hospital, Munster, Germany.
      INTERVENTIONS: Of 73 randomized patients, 37 were control subjects (who received
      general anesthesia only) and 36 were in the group who received general anesthesia
      and high TEA. MAIN OUTCOME MEASURES: The primary outcome measure was regional
      left ventricular function after myocardial revascularization, assessed by
      transesophageal echocardiography. We further determined the plasma concentrations
      of cardiac troponin I and atrial and brain natriuretic peptides. Secondary
      outcome measures were postoperative complications recorded to 14 days and
      mortality recorded to 720 days. RESULTS: High TEA was effective in all patients
      of this group, the somatosensory block extended from T1 through T7 vertebrae.
      Regional left ventricular function was significantly improved (mean [SD] global
      wall motion index, 0.74 [0.18] vs 0.38 [0.16]; P<.05), and cardiac troponin I
      concentrations were reduced by 72% (mean [SD], 5.7 [1.5] vs 1.6 [0.7] ng/mL,
      P<.05) in patients with high TEA. Natriuretic peptide concentrations peaked
      during reperfusion (atrial natriuretic peptide) and 24 hours after reperfusion
      (brain natriuretic peptide). High TEA reduced the mean (SD) peak concentrations
      of atrial natriuretic peptide by 54% (211 [63] vs 98 [33] ng/mL, P =.03) and
      brain natriuretic peptide by 43% (189 [39] vs 108 [21] ng/mL, P =.01). One of 36
      patients who received high TEA and 3 of 37 controls died. CONCLUSIONS: Reversible
      cardiac sympathectomy by high TEA improves regional left ventricular function and
      reduces postoperative ischemia after coronary artery bypass grafting. These
      effects of high TEA may improve the long-term outcome after myocardial
      revascularization.

PMID- 14662527
TI  - A tradition of national service in times of crisis.

PMID- 14662528
TI  - Colonic propulsive impairment in intractable slow-transit constipation.
AB  - HYPOTHESIS: Intractable constipation, especially of the slow-transit subtype, may
      represent several pathophysiologic entities with a common final symptomatic
      appearance. An overall impairment of colonic propulsive activity may represent a
      major disease mechanism. DESIGN: Case series. SETTING: Tertiary university
      hospital. SUBJECTS: Twenty-nine severely constipated patients with clinical and
      homogeneous features of slow-transit constipation that were unresponsive to
      conventional medical measures and 16 age-matched healthy volunteers.
      INTERVENTIONS: Twenty-four-hour manometric recordings obtained in patients and
      controls to assess high- and low-amplitude colonic propulsive activity. RESULTS:
      Compared with controls, patients showed heavily reduced high-amplitude propagated
      activity (average, <1 event per subject per day). No differences were found in
      low-amplitude propagated activity. CONCLUSIONS: Patients with severe constipation
      that is refractory to medical treatment may display an important reduction of
      colonic forceful propulsive activity. This may justify a surgical approach, which
      may offer the best results in such patients. It is, however, important to obtain
      thorough physiologic documentation before such a drastic approach is considered.
      The residual low-amplitude propulsive activity might represent a partially
      compensatory mechanism in these patients. Studies in more homogeneous groups of
      such patients are needed.

PMID- 14662529
TI  - National variation in operative mortality rates for esophageal resection and the
      need for quality improvement.
AB  - HYPOTHESIS: Operative mortality rates for esophageal resection vary across
      hospital volume groups in a nationally representative sample of hospitals.
      DESIGN: Cross-sectional study of all adult patients in the Nationwide Inpatient
      Sample who underwent esophageal resection from 1995 through 1999 (N = 3023).
      Operative mortality was determined for hospital volume quartiles (low, <3 per
      year; medium, 3-5 per year; high, 6-16 per year; very high, >16 per year).
      Multiple logistic regression of in-hospital mortality was used for case-mix
      adjusted analyses. SETTING: Hospitals performing at least 1 esophageal resection
      from 1995 through 1999 in the Nationwide Inpatient Sample. PATIENTS: Patients
      having esophageal resection from 1995 through 1999 in the Nationwide Inpatient
      Sample. RESULTS: Overall mortality was 8.2% and varied 3-fold from 11.8% to 3.7%
      across hospital volume groups (P<.001). In the case-mix-adjusted multivariate
      analysis, having surgery at a low-volume hospital (odds ratio, 2.9; 95%
      confidence interval, 1.7-4.9; P<.001) or medium-volume hospital (odds ratio, 2.4;
      95% confidence interval, 1.4-4.3; P =.002) was associated with an increased risk
      of mortality compared with the reference group of very high-volume hospitals. The
      effect of volume on mortality was significant for both malignant and benign
      disease. Given the absolute risk difference of 8.1% between very high- and low
      volume hospitals, only 12 patients would need to be referred to prevent 1 death
      after esophageal resection. CONCLUSIONS: The operative mortality rate for
      esophageal resection varies across hospitals in the United States. To improve the
      quality of care and reduce operative mortality rates for patients in need of
      esophageal surgery, patients should either be referred to higher-volume
      hospitals, or quality improvement should be directed at lower-volume hospitals.

PMID- 14662530
TI  - Changes in morbidity after pancreatic resection: toward the end of completion
      pancreatectomy.
AB  - HYPOTHESIS: Advances in specialized centers for pancreatic diseases have improved
      surgical morbidity and outcome. In the past, postoperative local complications
      (pancreatic fistulae) were causing most of the mortality. Now, more patients
      experience postoperative complications related to their comorbidity. DESIGN: To
      report a prospective audit of a single center's experience with pancreatic
      resection during an 8-year period. SETTING: Tertiary referral center focused on
      pancreatic diseases. PATIENTS AND INTERVENTIONS: Six hundred seventeen
      consecutive patients underwent pancreatectomy between November 1, 1993, and
      August 31, 2001. The series included 468 pancreatic head resections (76%), 25
      total pancreatectomies (4%), 88 left-sided resections (14%), and 36 others (6%).
      MAIN OUTCOME MEASURES: Morbidity after pancreatic resection. RESULTS:
      Postoperative in-hospital mortality was 1.6%, and the additional operation rate
      was 4.1%. Four patients died of surgical complications and 6 of systemic
      complications. Systemic morbidity was 18% and consisted primarily of
      cardiopulmonary complications (13%). The most frequent postoperative complication
      was delayed gastric emptying (14%), which caused significant prolongation of the
      hospital stay. No patients died of a postoperative pancreatic fistula, which
      occurred in 3.2%, and no completion pancreatectomies were necessary. CONCLUSIONS:
      Pancreatic resections can be performed with considerable safety and a low rate of
      pancreatic complications. More patients die of systemic complications than in the
      past, which increases the demand for precise preoperative patient selection.
      Completion pancreatectomy should no longer be considered in patients with a
      pancreatic fistula.

PMID- 14662531
TI  - Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes
      and implications for therapy.
AB  - HYPOTHESIS: An aggressive strategy that includes extended lymphadenectomy and
      vein resection may improve the results of surgical treatment of pancreatic head
      cancer. DESIGN: Nonrandomized control trial. SETTING: Tertiary care referral
      center. PATIENTS: The study included 149 consecutive patients undergoing
      macroscopically curative resection for periampullary adenocarcinoma from January
      1, 1988, to December 31, 1998. INTERVENTIONS: A standard resection was performed
      in 122 cases; an extended lymphadenectomy in 37. Twenty-four patients underwent
      venous resection. MAIN OUTCOME MEASURES: Data on surgical mortality, morbidity,
      and postoperative outcome, pathological findings, and long-term survival were
      analyzed. RESULTS: In-hospital and 60-day operative mortality was 5.4%. Morbidity
      was 37.5%. Mortality, morbidity, and postoperative stay were nonsignificantly
      modified by extended lymphadenectomy or venous resection. Extended resection
      permitted the identification of a significantly higher percentage of nodal
      metastases beyond the peripancreatic node groups. In patients undergoing vein
      resection, a significantly higher rate of positive retroperitoneal margin was
      found. In the 100 patients with ductal adenocarcinoma, the median overall
      survival and the 5-year actuarial survival rate were 15 months and 8.4%,
      respectively. A trend toward a better survival was observed in the first 2 years
      after operation in the extended resection group compared with the standard
      resection group. Nodal status was the most powerful predictor of overall survival
      by multivariate analysis. CONCLUSIONS: Extended lymphadenectomy and vein
      resection did not adversely affect postoperative mortality and morbidity.
      Patients who required a vein resection were less likely to receive a
      microscopically curative pancreatectomy. Extended resection permitted better
      pathological staging and was associated with an early advantage in survival, but
      long-term survival was possible only in patients with favorable prognostic
      factors.

PMID- 14662532
TI  - Effect of genetic cancer risk assessment on surgical decisions at breast cancer
      diagnosis.
AB  - HYPOTHESIS: Breast cancer gene (BRCA) mutation status affects patients' surgical
      decisions when genetic cancer risk assessment is offered at the time of breast
      cancer diagnosis, prior to definitive treatment. PATIENTS AND INTERVENTIONS:
      Outcomes following genetic cancer risk assessment were studied for women newly
      diagnosed as having breast cancer who were prospectively enrolled in an
      institutional review board-approved hereditary cancer registry during a 1-year
      sampling frame. BRCA gene analysis was offered to subjects with a calculated
      mutation probability of 10% or higher. Review of medical records and telephone
      survey were used to document surgical treatment decisions following genetic
      cancer risk assessment. RESULTS: Thirty-seven of 233 women in the registry were
      enrolled at the time of a breast cancer diagnosis. The interval from diagnosis to
      genetic cancer risk assessment ranged from 3 to 60 days. The mean calculated
      probability of a BRCA gene mutation was 21% across the cohort. Two women were not
      tested because of low prior probabilities of mutation detection, and 3 declined
      owing to intercurrent psychological stressors. Of the remaining 32 patients, no
      BRCA gene mutation was detected in 22 (69%), 3 (9%) were found to carry a variant
      of uncertain significance, and 7 (22%) had a deleterious mutation. All 7 subjects
      with a deleterious mutation opted for bilateral mastectomy, whereas 20 of 22
      patients with negative test results chose stage-appropriate treatment (P<.001).
      CONCLUSIONS: Genetic cancer risk assessment at the time of breast cancer
      diagnosis significantly affected women's treatment decisions. Although need and
      feasibility are demonstrated, the logistics of genetic cancer risk assessment
      during breast cancer diagnosis prove challenging.

PMID- 14662533
TI  - Are solitary breast papillomas entirely benign?
AB  - HYPOTHESIS: Solitary breast papillomas are potentially malignant and are
      associated with a higher risk of breast cancer. DESIGN: Retrospective review of
      all pathological reports containing breast papilloma (1983-2000) and review of
      selected specimens. SETTING: Tertiary, referral, university-affiliated medical
      center. PARTICIPANTS: Ninety-five women with a breast specimen containing a
      papilloma or papillomatosis. Patients with overt papillary carcinoma without
      papilloma were excluded. INTERVENTION: All histopathological characteristics of
      the papilloma and the surrounding tissue were noted. The incidence of malignant
      and other proliferative histopathological findings were analyzed, comparing
      solitary ductal papilloma cases to multiple papilloma cases. The Fisher exact
      test and chi2 test were applied for statistical analysis. MAIN OUTCOME MEASURES:
      Surgical removal of solitary ductal papillomas should include margins wide enough
      to secure removal of any proliferative tissue within or around the papilloma and
      to enable thorough evaluation of the risk for future breast cancer. RESULTS:
      Solitary papillomas were associated with breast carcinoma in 7 patients (10%) in
      this series. An additional 9% (n = 6) presented with invasive or noninvasive
      carcinoma within the papilloma. Atypical papilloma was noted in 6% of patients (n
      = 4). The risk of associated malignancy was not significantly different between
      solitary ductal papilloma and multiple papilloma. CONCLUSION: Increased risk of
      breast cancer is associated with all forms of papilloma.

PMID- 14662534
TI  - Cost-effectiveness of defunctioning stomas in low anterior resections for rectal
      cancer: a call for benchmarking.
AB  - HYPOTHESIS: Anastomotic leakage is the most important cost driver in patients who
      undergo low anterior resection (LAR) for rectal cancer. Creating defunctioning
      stomas to protect colorectal anastomoses may also have a major effect on the
      overall costs. Unselected creation of defunctioning stomas in most of these
      patients may be associated with higher overall costs compared with a program that
      has a low rate of defunctioning stomas and an acceptable anastomotic leakage
      rate. DESIGN: Cost-effectiveness analysis. SETTING: Secondary referral center.
      PATIENTS: Performing a cost analysis from the viewpoint of a hospital provider,
      we reviewed data of 70 consecutive patients who underwent LARs with (n = 19) or
      without (n = 51) a defunctioning colostomy. A scenario analysis was performed
      using data derived from the medical literature to assess a plausible range of
      leakage and stoma rates. MAIN OUTCOME MEASURE: Costs per treatment option and
      incremental cost-effectiveness ratio according to various treatment scenarios.
      RESULTS: Performing an LAR without a stoma and no anastomotic leakage is
      associated with significantly lowest costs (8.400 euro; P<.001) compared with
      patients with a stoma (13.985 euro) and patients with anastomotic leakage (42.250
      euro). The most important cost drivers were anastomotic leakages and
      defunctioning stomas. A leakage rate of 16.5% in patients without a stoma would
      be necessary to balance the overall costs of patients with stomas. The
      incremental cost-effectiveness ratio would be 158.705 euro and 60.915 euro per
      leak, respectively, avoided in patients with defunctioning stomas assuming a
      leakage rate lower than 3% and 6%, respectively, in patients who did not undergo
      a colostomy. A 1-way sensitivity analysis revealed that duration and costs of
      intensive care unit care were the only factors that may considerably alter our
      results. CONCLUSIONS: A suggested benchmark for an LAR should be a rate of 10% or
      less for defunctioning stomas and anastomatic leaks; that would limit the overall
      costs to 12,000 euro per patient treated. Against the background of a lack of
      universally valid criteria for the creation of defunctioning stomas, our aim
      should be to reduce the rate of defunctioning stomas because of their major
      effect on the overall costs especially in programs with a lower leakage rate.
      Higher leakage rates despite higher stoma rates depend more on the skill of the
      surgeon than on the characteristics of the patient and higher leakage should lead
      to a change in surgical technique strategy.

PMID- 14662535
TI  - Vaginal reconstruction following resection of primary locally advanced and
      recurrent colorectal malignancies.
AB  - HYPOTHESES: Vertical rectus abdominus myocutaneous flap reconstruction
      facilitates healing within the radiated pelvis and preserves the possibility of
      subsequent sexual function in patients with colorectal cancer who require partial
      or complete resection of the vagina. DESIGN: A retrospective review of a
      consecutive series of patients. SETTING: A tertiary referral center. PATIENTS:
      All patients undergoing surgical treatment of locally advanced or recurrent
      colorectal cancer and vertical rectus abdominus myocutaneous flap reconstruction
      of the vagina. INTERVENTION: Vertical rectus abdominus myocutaneous flap
      reconstruction. MAIN OUTCOME MEASURES: Operative feasibility, complications, and
      sexual function. RESULTS: Twelve patients underwent extended resection for
      primary locally advanced or recurrent colorectal cancer including total or near
      total vaginectomy. Median age was 47 years. Tumors included 9 rectal
      adenocarcinomas, 2 anal squamous cell carcinomas, and 1 recurrent cecal
      adenocarcinoma. Surgical procedures included 8 abdominoperineal resections with
      posterior exenteration; resection of pelvic tumor and partial vaginectomy in 2
      patients with previous abdominoperineal resection; 1 total exenteration; and 1
      total proctocolectomy with posterior exenteration. The average operative time for
      tumor extirpation, irradiation, and reconstruction was more than 9 hours and all
      patients required blood transfusions. Despite 2 patients having superficial
      necrosis and 4 having mild wound infections, no patient required reoperation and
      all achieved complete healing. Five patients reported resuming sexual
      intercourse. CONCLUSIONS: The vertical rectus abdominus myocutaneous flap can be
      successfully used for vaginal reconstruction following resection of locally
      advanced colorectal cancer. It provides nonirradiated, vascularized tissue that
      fills the pelvic dead space, allows for stomal placement, and provides a chance
      for sexual function.

PMID- 14662536
TI  - Community characteristics and demographic information as determinants for a
      hospital-based injury prevention outreach program.
AB  - HYPOTHESIS: To focus the efforts of a hospital-based injury prevention outreach
      program, information on patient demographics, community characteristics, and
      catchment area must be known. DESIGN AND SETTING: Evaluation of prospectively
      collected data maintained in the Trauma Registry of a level I university-based
      trauma center. PATIENTS AND MAIN OUTCOME MEASURES: Demographics, mechanism of
      injury, mortality, and home ZIP codes of patients admitted to the Adult Trauma
      Service, The Johns Hopkins Medical Institution, Baltimore, Md, were compared for
      2 separate calendar years, at 2 years before (1995) and at 2 years after (2000)
      the implementation of a dedicated trauma program that includes an injury
      prevention outreach program. RESULTS: The list of common patient ZIP codes varied
      minimally from 1995 to 2000. The 18 most common ZIP codes represent (1) 80% of
      patients, (2) total area of 99 square miles (257.4 km2) (5.7-mile [9.1-km]
      radius), and (3) a region with a mean household income that is 67% of the
      statewide median. An increasingly disproportionate percentage of patients with
      gunshot wounds (GSWs) were the youngest patients (ages 15-24 years) treated by
      the Adult Trauma Service. While overall survival of trauma patients improved in
      2000, no improvement was seen among patients with GSWs. Over half of the
      nonsurviving patients (37/65 [57%]) seen in 2000 and more than two thirds of
      patients with lethal GSWs (25/37 [67.6%]) were declared dead in the emergency
      department, suggesting nonpreventability from a clinical care standpoint.
      CONCLUSIONS: The catchment area represented by the bulk of patients admitted to a
      level I urban trauma center is compact and economically disadvantaged. While
      overall trauma mortality has decreased, GSWs are more lethal and prevalent in
      teenagers and young men. This identifies violence prevention as an area of
      emphasis.

PMID- 14662537
TI  - Explaining racial variation in lower extremity amputation: a 5-year retrospective
      claims data and medical record review at an urban teaching hospital.
AB  - HYPOTHESIS: Population-based hospital data indicate that African American
      patients undergo major lower extremity (LE) amputation 2 to 3 times more
      frequently than white patients. Some have attributed this to a lack of access to
      LE revascularization procedures by African American patients. To determine the
      likelihood that racial disparities in amputation rates are related to treatment
      choice, this study examines rates of primary amputation (major amputation without
      any previous attempt at revascularization) and repeat amputation. DESIGN AND
      SETTING: Two-step case-control study, reviewing experience at a large midwestern
      teaching hospital. First, administrative discharge data for all 1127 patients
      undergoing LE arterial bypass graft, angioplasty, or major amputation from
      January 1, 1995, to February 1, 2000, were used to analyze racial differences in
      the risk of admission for major amputation vs revascularization. Medical records
      were then reviewed for an approximate full sample of 60 African American major
      amputees and a random sample of 60 (two thirds of the total) white major
      amputees. Racial disparities in frequency of primary and repeat amputation were
      analyzed, controlling for age, sex, and diabetes mellitus status. OUTCOME
      MEASURES: Among all patients admitted for LE ischemia, outcome measures were the
      odds of amputation vs revascularization, and among a sample of African American
      and white amputees, the odds of primary vs repeat major amputation. RESULTS:
      Among all patients hospitalized for LE ischemia, African American patients were
      younger (P<.05), more often female (P<.01), and more likely to undergo major
      amputation (odds ratio, 1.68; P =.005). However, after adjusting for age, sex,
      and diabetes mellitus prevalence, the analysis revealed an equal likelihood of
      primary amputation among African Americans and whites. Repeat amputees were 2.5
      times more likely to be African American than white (P =.04). CONCLUSION: The
      racial disparity at the study institution was primarily due to African American
      patients undergoing repeat major amputation at a significantly higher rate than
      whites.

PMID- 14662538
TI  - Selective non-stapling of mesh during unilateral endoscopic total extraperitoneal
      inguinal hernioplasty: a case-control study.
AB  - HYPOTHESIS: Selective non-stapling of the mesh during unilateral endoscopic total
      extraperitoneal inguinal hernioplasty (TEP) may reduce postoperative pain and
      morbidity rate. DESIGN: Case-control study. SETTING: Division of general surgery
      at a university-affiliated teaching hospital. PATIENTS: Two hundred patients who
      underwent TEP. INTERVENTION: Endoscopic total extraperitoneal inguinal
      hernioplasty with and without stapling the mesh. The mesh was stapled when the
      diameter of the hernial defect was greater than 4 cm or there was an inadequate
      overlap of the defect by the mesh. MAIN OUTCOME MEASURES: Postoperative pain
      score and morbidity rate were compared between patients who had stapling and
      selective non-stapling of the mesh during TEP. RESULTS: Demographic features,
      hernia types, and mean operative times of the 2 groups were comparable.
      Postoperative pain scores upon coughing from the day of operation to
      postoperative day 6 were lower in patients who had not had the mesh stapled, but
      the difference was not statistically significant. Comparisons of the mean length
      of hospital stay, postoperative morbidity, and time taken to resume normal
      activities showed no significant difference between the 2 groups. With a mean
      follow-up of 1 year, no neuralgia or recurrence was noted in either group during
      follow-up. CONCLUSIONS: Selective non-stapling of the mesh did not confer short
      term benefits, such as reduced postoperative pain and morbidity, compared with
      those who had routine stapling of the mesh during TEP. For patients with a
      hernial defect measuring less than 4 cm, TEP can be performed without stapling
      the mesh. The selective non-stapling strategy also helps to reduce the cost of
      the operation and the potential for nerve entrapment.

PMID- 14662539
TI  - Health care utilization after medical and surgical therapy for gastroesophageal
      reflux disease: a population-based study, 1996 to 2000.
AB  - HYPOTHESIS: Patients who undergo surgical treatment for gastroesophageal reflux
      disease (GERD) will use fewer health care resources than those who continue to be
      treated medically during the same follow-up period. DESIGN: Matched cohort study
      of patients with a diagnosis of GERD receiving surgical therapy or medical
      therapy. SETTING: Tennessee Medicaid (TennCare) program from 1996 through 2000.
      PATIENTS: Population-based sample of 7635 TennCare enrollees with a diagnosis of
      GERD served as the underlying population. Of these, 111 surgical patients who
      underwent fundoplication in 1996 met inclusion criteria. The 200 patients in the
      medically treated cohort were randomly matched to patients in the surgical cohort
      by demographic characteristics and previous use of acid-suppressing drugs.
      INTERVENTIONS: The surgical group all underwent fundoplication in 1996. The
      medical group was treated without fundoplication. MAIN OUTCOME MEASURES: Health
      care utilization (medication use, outpatient visits, hospitalizations, and
      diagnostic studies) for each cohort through December 2000. RESULTS: In the 4-year
      follow-up period, the surgical group had fewer GERD-related outpatient physician
      visits (5.5 +/- 6.9 visits vs 6.7 +/- 6.1 visits; P =.10). Utilization of other
      types of outpatient and inpatient care was similar. During each year of follow
      up, the proportion of persons using GERD medication was lower in the surgical
      group. (0.67 vs 0.93 in year 1, 0.67 vs 0.91 in year 2, 0.72 vs 0.85 in year 3,
      and 0.74 vs 0.90 in year 4). CONCLUSION: The utilization of health care resources
      in patients treated surgically for GERD is associated with a modest decrease in
      the use of GERD-related medications and GERD-related visits.

PMID- 14662540
TI  - Follicular variant of papillary thyroid carcinoma: a long-term follow-up.
AB  - HYPOTHESIS: The clinical behavior of the follicular variant of papillary thyroid
      carcinoma (FVPTC) is similar to pure papillary thyroid carcinoma (PPTC) and
      completely different from follicular thyroid carcinoma (FTC). DESIGN:
      Retrospective analysis of prospectively documented data. SETTING: Referral center
      of a university hospital. PATIENTS: Two hundred thirty-seven consecutive patients
      with follicular cell-derived thyroid carcinomas were operated on in our
      institution during a 15-year period, from January 1, 1980, to December 31, 1994.
      Of the 154 PTC patients, 37 (24%) had FVPTC. The mean follow-up was 128.2 months
      (10.7 years). MAIN OUTCOME MEASURES: Demographic features, tumor characteristics,
      local and distant spread, persistence or recurrence of disease, and carcinoma
      related mortality were compared between the groups with FVPTC, PPTC, and non
      Hurthle cell FTC (NHFTC). RESULTS: The frequency of multicentricity was
      significantly higher in the FVPTC group than in the PPTC group (P =.03) or in the
      NHFTC group (P =.01) (12 [32%] of 37 patients vs 17 [15%] of 117 patients vs 6
      [10%] of 58 patients, respectively). The incidence of cervical lymph node
      metastases was lower in the FVPTC group than in the PPTC group (P =.30) and
      higher than in NHFTC group (P =.004) (12 [32%] of 37 patients vs 53 [45%] of 117
      patients vs 6 [10%] of 58 patients, respectively). At diagnosis, no patient with
      FVPTC showed distant metastases, compared with 5 patients (4%) with PPTC (P =.34)
      and 19 (33%) with NHFTC (P<.001). There was no carcinoma-related death in the
      FVPTC group. The strikingly poorer prognosis for the NHFTC group was
      statistically significant (P<.001), whereas the difference in carcinoma-specific
      survival between the PPTC and the FVPTC groups did show a trend toward better
      survival in the FVPTC group. CONCLUSION: The clinical behavior of the FVPTC group
      did not differ significantly from that of the PPTC group, whereas compared with
      the NHFTC group, the FVPTC group showed statistically significant differences for
      most of the analyzed variables.

PMID- 14662541
TI  - Hepatic portal gas in adults: review of the literature and presentation of a
      consecutive series of 11 cases.
AB  - BACKGROUND: Hepatic portal venous gas (HPVG) in adults is a rare entity. The
      underlying pathologic condition is usually an intestinal ischemia, but it has
      been reported in association with a variety of conditions. HYPOTHESIS:
      Miscomprehension of the underlying pathologic conditions has led to some
      confusion in the literature concerning its etiology, diagnostic methods, and
      clinical consequences. SETTING: Centre Hospitalier et Universitaire Vaudois,
      Lausanne, Switzerland, and District Hospital of Morges, Morges, Switzerland.
      METHOD: Between February 1, 1995, and May 30, 2000, eleven cases of HPVG were
      treated. These cases were retrospectively reviewed, together with a review of the
      literature to define the clinical significance of HPVG, the role of the computed
      tomographic scan, and the necessity of performing systematic emergency
      exploratory surgery. RESULTS: Two groups have to be distinguished-those who have
      HPVG with associated pneumatosis intestinalis and those who have HPVG without
      associated pneumatosis intestinalis. When associated with pneumatosis
      intestinalis, the cause is usually an intestinal ischemia and in a symptomatic
      patient it justifies systematic exploratory surgery. An abdominal computed
      tomographic scan including lung window settings to better identify air in the
      bowel wall will distinguish between these 2 groups. Pneumatosis intestinalis and
      HPVG due to bowel ischemia do not allow prediction of the severity of bowel wall
      damage. CONCLUSIONS: The cause of HPVG without pneumatosis intestinalis is
      variable. Good knowledge of the possible causes combined with the clinical
      picture and the abdominal computed tomographic scan is required to correctly
      identify the underlying cause of HPVG and to avoid unnecessary surgery.

PMID- 14662542
TI  - Potential margin distortion in breast tissue by specimen mammography.
AB  - HYPOTHESIS: There is a potential for margin distortion associated with the use of
      a compression plate in specimen mammography (SM) devices. DESIGN: Prospective
      observational study. SETTING: Two tertiary care teaching hospitals. PATIENTS:
      Breast biopsy tissue dimensions were recorded in 15 patients undergoing 18
      operations before and after SM (group 1). After review of these data, we
      supervised the positioning of tissue for SM and obtained measurements for 12
      breast biopsy specimens from 12 additional patients before and after SM (group
      2). MAIN OUTCOME MEASURES: Breast biopsy specimen dimensions recorded before and
      after SM, including length, width, and depth (the specimen depth along the axis
      of compression); data on age, menopausal status, hormone therapy, and the
      presence or absence of calcifications or tumor; and a national telephone survey
      on technique and understanding of SM at 21 institutions. RESULTS: The specimen
      depth in group 1 was markedly decreased (P<.001) along the axis of compression.
      The mean length and width of the specimens were marginally increased by the
      effect of the SM device. Specimen depth in group 2 was unchanged when minimal
      pressure was used on the compression plate. Tissue was adequately immobilized in
      both groups, and all lesions were identified by SM. Our survey revealed that 71%
      of hospitals reported using firm compression in SM, and diverse techniques were
      employed. CONCLUSIONS: This study demonstrates the potential for specimen margin
      distortion with compression SM. Undue specimen compression is common in routine
      SM. Surgeon oversight in the method of securing the specimen within the SM
      container will minimize or avoid the potential for margin distortion.

PMID- 14662544
TI  - Extended esophagectomy with 3-field lymph node dissection for esophageal cancer.
AB  - OBJECTIVE: To review the surgical outcomes of extended esophagectomy with 3-field
      lymph node dissection (3FLND) for esophageal cancer. DATA SOURCES: Only articles
      written in English and written after 1980 were selected from MEDLINE. The
      following terms were identified: 3FLND, extensive or extended lymph node
      dissection (lymphadenectomy), radical lymph node dissection, cervical lymph node
      dissection, and extended or radical esophagectomy in esophageal cancer. STUDY
      SELECTION: There were no exclusion criteria for published information relevant to
      the topic. The most representative articles were selected when there were several
      articles from the same institution. Case reports were excluded. DATA EXTRACTION:
      Twenty-six articles were finally col-lected from MEDLINE. Eleven articles were
      also selected from reference lists of the pertinent literature. DATA SYNTHESIS:
      The collected information was organized. CONCLUSIONS: The conclusions drawn from
      those articles showed that extended esophagectomy with 3FLND would be a safe
      procedure in experienced hands, with low morbidity and acceptable mortality
      rates. When strict patient selection criteria were maintained, this procedure
      reduced locoregional recurrence and improved long-term survival rates. Although
      the therapeutic value of 3FLND is unproved in a randomized trial, extended
      esophagectomy with 3FLND would be the treatment of choice in selected patients.

PMID- 14662543
TI  - Sex differences in hepatic heme oxygenase expression and activity following
      trauma and hemorrhagic shock.
AB  - HYPOTHESIS: Sex differentially influences heme oxygenase (HO) expression
      following trauma and hemorrhagic shock. DESIGN: Prospective controlled animal
      study. SETTING: A university laboratory. INTERVENTIONS: Female Sprague-Dawley
      rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm
      midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean
      arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which
      they were resuscitated with Ringer lactate solution (4 x the shed blood volume).
      In another group of animals, tin protoporphyrin IX was used to block HO activity.
      MAIN OUTCOME MEASURES: Liver samples were collected for analysis of HO expression
      and activity, plasma samples were collected, and alanine transaminase levels were
      determined 5 hours after resuscitation. Portal pressure and bile production were
      measured in vivo 5 hours after resuscitation. RESULTS: Trauma and hemorrhage
      induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in
      proestrus females compared with males. Hepatic expression of HO2 (a constitutive
      isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in
      vivo with tin protoporphyrin IX abolished the sex differences caused by diverse
      HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal
      pressure, decreased bile production, and increased alanine transaminase to
      similar levels in proestrus females and males following trauma and hemorrhage.
      CONCLUSIONS: Sex influences the hepatic expression of HO1 following trauma and
      hemorrhage. The enhanced induction of HO1 expression and activity in females
      after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury
      by maintaining microcirculation via the increased production of carbon monoxide.

PMID- 14662545
TI  - Cholecystocolic fistula and large-bowel obstruction due to gallstone ileus.

PMID- 14662546
TI  - Leon Goldman: "The Coach".

PMID- 14662547
TI  - Surgery in Singapore.
AB  - Since Singapore became an independent nation about 50 years ago, remarkable
      progress has been made in the development and organization of the health care
      system, specialty services, graduate training, and medical research. The
      primitive health care service under the British colonial service before the
      Second World War which was further ravaged in the 1940s by the Japanese
      occupation has been radically transformed in a short period. Singapore has a
      modern health care service, excellent hospital facilities, an affordable health
      financing system, adequate medical manpower including specialists, and a
      postgraduate organization for the training of medical specialists. The
      advancement in surgical services has reached a high level where all forms of
      modern surgery, including laparoscopic and endoscopic operations, are routine and
      major bone and joint replacements, heart and liver transplantations, and complex
      neurosurgical and craniofacial operations are frequently carried out.

PMID- 14662549
TI  - Still life with open Bible and Zola's La Joie de Vivre.

PMID- 14662550
TI  - Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies.
AB  - CONTEXT: There are many published twin studies of schizophrenia. Although these
      studies have been reviewed previously, to our knowledge, no review has provided
      quantitative summary estimates of the impact of genes and environment on
      liability to schizophrenia that also accounted for the different ascertainment
      strategies used. OBJECTIVE: To calculate meta-analytic estimates of heritability
      in liability and shared and individual-specific environmental effects from the
      pooled twin data. DATA SOURCES: We used a structured literature search to
      identify all published twin studies of schizophrenia, including MEDLINE,
      dissertation, and books-in-print searches. STUDY SELECTION: Of the 14 identified
      studies, 12 met the minimal inclusion criteria of systematic ascertainment. DATA
      SYNTHESIS: By using a multigroup twin model, we found evidence for substantial
      additive genetic effects-the point estimate of heritability in liability to
      schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was
      consistent evidence across these studies for common or shared environmental
      influences on liability to schizophrenia-joint estimate, 11% (95% confidence
      interval, 3%-19%). CONCLUSIONS: Despite evidence of heterogeneity across studies,
      these meta-analytic results from 12 published twin studies of schizophrenia are
      consistent with a view of schizophrenia as a complex trait that results from
      genetic and environmental etiological influences. These results are broadly
      informative in that they provide no information about the specific identity of
      these etiological influences, but they do provide a component of a unifying
      empirical basis supporting the rationality of searches for underlying genetic and
      common environmental etiological factors.

PMID- 14662551
TI  - Decrements in volume of anterior ventromedial temporal lobe and olfactory
      dysfunction in schizophrenia.
AB  - CONTEXT: Patients with schizophrenia exhibit olfactory deficits, but it is
      unclear whether these represent a specific abnormality. The link between
      olfactory impairments and regional brain abnormalities has yet to be established.
      OBJECTIVES: To determine whether patients with schizophrenia exhibit volumetric
      deficits in the anterior ventromedial temporal lobe, the target for neuronal
      inputs from the olfactory bulb, and whether these are related to olfactory
      performance deficits. DESIGN: A cohort study of patients and healthy control
      subjects who underwent both 1-mm spoiled-gradient echo magnetic resonance imaging
      and behavioral tests of olfaction and memory. SETTING: Schizophrenia Research
      Center at the University of Pennsylvania, Philadelphia. PARTICIPANTS: Fifty-two
      patients with a DSM-IV diagnosis of schizophrenia and 38 healthy control
      subjects. Individuals were excluded for history of head trauma, significant
      substance abuse, and medical conditions affecting brain function or olfactory
      capacity. MAIN OUTCOME MEASURES: Gray matter volumes of the left and right
      temporal poles and the perirhinal and entorhinal cortexes; olfactory threshold
      detection sensitivity and identification test scores; composite indexes of verbal
      and spatial memory ability. RESULTS: Patients had reduced volumes, relative to
      cranial size, in left (P =.003) and right (P =.01) perirhinal and left (P =.002)
      and right (P =.002) entorhinal cortexes, but not in the temporal pole.
      Perirhinal, but not entorhinal, cortical volume decrement was associated with
      decreased olfactory threshold sensitivity. Neither region was associated with
      impaired memory performance. CONCLUSIONS: Patients with schizophrenia have
      reduced cortical volumes in brain regions that receive afferents directly from
      the olfactory bulb. Behavioral olfactory deficits are related to structural brain
      abnormalities in these regions.

PMID- 14662552
TI  - Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder.
AB  - BACKGROUND: The purported functions of medial temporal lobe structures suggest
      their involvement in the pathophysiology of bipolar disorder (BD). Previous
      reports of abnormalities in the volume of the amygdala and hippocampus in
      patients with BD have been inconsistent in their findings and limited to adult
      samples. Appreciation of whether volumetric abnormalities are early features of
      BD or whether the abnormalities represent neurodegenerative changes associated
      with illness duration is limited by the paucity of data in juvenile samples.
      OBJECTIVE: To investigate amygdala and hippocampal volume in adults and
      adolescents with BD. SETTING AND PARTICIPANTS: Subjects included 36 individuals
      (14 adolescents and 22 adults) in outpatient treatment for BD type I at a
      university hospital or Veterans Affairs medical center or in the surrounding
      community, and 56 healthy comparison subjects (23 adolescents and 33 adults).
      DESIGN AND MAIN OUTCOME MEASURES: Amygdala and hippocampal volumes were defined
      and measured on high-resolution anatomic magnetic resonance imaging scans. We
      used a mixed-model, repeated-measures statistical analysis to compare amygdala
      and hippocampal volumes across groups while covarying for total brain volume,
      age, and sex. Potential effects of illness features were explored, including
      rapid cycling, medication, alcohol or other substance dependence, duration, and
      mood state. RESULTS: For both the amygdala and hippocampal regions, we found an
      overall significant volume reduction in the BD compared with the control group
      (P<.0001). Amygdala volume reductions (15.6%) were highly significant (P<.0001).
      We observed a nonsignificant trend (P =.054) toward reductions in hippocampal
      volumes of lesser magnitude (5.3%). Effects of illness features were not
      detected. CONCLUSIONS: These results suggest that BD is associated with decreased
      volumes of medial temporal lobe structures, with greater effect sizes in the
      amygdala than in the hippocampus. These abnormalities are likely manifested early
      in the course of illness, as they affected adolescent and adult subjects
      similarly in this sample.

PMID- 14662553
TI  - Individual and familial risk factors for bipolar affective disorders in Denmark.
AB  - BACKGROUND: Few population-based studies have addressed risk factors for bipolar
      affective disorder. OBJECTIVE: To study the possible association between bipolar
      affective disorder and history of mental illness in a parent or sibling;
      urbanicity of birth place; season of birth; sibship characteristics, including
      birth order; influenza epidemics during pregnancy; and early parental loss.
      DESIGN: We used a population-based cohort of 2.1 million individuals based on
      data from the Danish Civil Registration System linked with the Danish Psychiatric
      Central Register. SETTING: Nationwide population-based sample of all individuals
      hospitalized or in outpatient clinic contact for the first time with bipolar
      affective disorder. Patients Overall, 2299 individuals were first diagnosed with
      bipolar affective disorder during the 31.8 million person-years of follow-up.
      RESULTS: Risk of bipolar affective disorder was associated with a history of
      bipolar affective disorder as well as other psychiatric disorders, including
      schizophrenia and schizoaffective disorder, in parents or siblings. People with a
      first-degree relative with bipolar affective disorder had a 13.63-fold (95%
      confidence interval, 11.81-15.71) increased risk of bipolar affective disorder.
      No other consistent associations were found with the exception of an association
      between early parental loss, in particular maternal, and bipolar affective
      disorder. Children who experienced maternal loss before their fifth birthday had
      a 4.05 (95% confidence interval, 1.68-9.77) increased risk of bipolar affective
      disorder. CONCLUSIONS: Early parental loss may represent both environmental and
      genetic risk factors for bipolar affective disorder. Most of the risk factors
      included in our study that previously have been associated with schizophrenia
      were not associated with bipolar affective disorder, supporting that the 2
      disorders may be at least partially separate etiological entities.

PMID- 14662554
TI  - A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment
      of acute mania.
AB  - BACKGROUND: This randomized controlled trial compares the efficacy and safety of
      olanzapine vs haloperidol, as well as the quality of life of patients taking
      these drugs, in patients with bipolar mania. METHODS: The design consisted of 2
      successive, 6-week, double-blind periods and compared flexible dosing of
      olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219). RESULTS:
      Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item
      Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for
      olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P
      =.15). For the subgroup of patients whose index episode did not include psychotic
      features, rates of remission were significantly greater for the olanzapine group
      compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an
      affective episode (mania and/or depression) occurred in 13.1% and 14.8% of
      olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to
      depression occurred significantly more rapidly with haloperidol than with
      olanzapine when using survival analysis techniques (P =.04), and significantly
      more haloperidol-treated patients experienced worsening of extrapyramidal
      symptoms, as indicated by several measures. Weight gain was significantly greater
      in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg,
      P<.001). The olanzapine group had significant improvement in quality of life on
      several dimensions compared with the haloperidol group. CONCLUSIONS: These data
      suggest that olanzapine does not differ from haloperidol in achieving overall
      remission of bipolar mania. However, haloperidol carries a higher rate of
      extrapyramidal symptoms, whereas olanzapine is associated with weight gain.

PMID- 14662555
TI  - Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and
      rejected.
AB  - CONTEXT: To understand the mechanism of action of antipsychotic drugs, it is
      critical to recognize the time course over which these medications take effect.
      Current models of antipsychotic action presume a "delayed onset" of action.
      OBJECTIVE: To test the delayed-onset hypothesis of antipsychotic action via a
      meta-analytic study. DATA SOURCES AND STUDY SELECTION: Double-masked studies that
      reported results from active or placebo-controlled trials of antipsychotic
      response during the first 4 weeks of treatment were selected. These studies were
      identified by searching MEDLINE, 1996 to 2001; the Cumulative Index to Nursing
      and Allied Health, 1982 to 2001; EMBASE, 1980 to 2001; the ACP Journal Club; the
      Cochrane Database of Systematic Reviews; and the Database of Abstracts of Reviews
      of Effectiveness. Leads from these sources were followed up by manual searches.
      DATA SYNTHESIS: Forty-two published studies, including 7450 patients and 119
      independent response vs time curves, were identified. Reductions in total scores
      on the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome
      Scale were 13.8% during week 1, 8.1% during week 2, 4.2% during week 3, and 4.7%
      during week 4. This pattern of "early-onset" improvement was present even after
      the estimated effect of placebo treatment was removed and when results were
      restricted to the psychotic subscales of the scales. CONCLUSIONS: This analysis
      rejects the commonly held hypothesis that antipsychotic response is delayed.
      Rather, these findings suggest that the antipsychotic response starts in the
      first week of treatment and accumulates over time. Furthermore, greater
      improvement occurs in the first 2 treatment weeks than in the subsequent 2
      treatment weeks. Proposed mechanisms of action of antipsychotic drugs need to
      account for this early-onset antipsychotic effect.

PMID- 14662556
TI  - Outpatient treatment of child and adolescent depression in the United States.
AB  - BACKGROUND: Although psychotherapy has traditionally been the dominant form of
      treatment for children and adolescents with depression, there has been a recent
      increase in the prescription of antidepressants for this age group. OBJECTIVE: To
      describe patterns of outpatient treatment for children and adolescents with
      depression. DESIGN AND SETTING: Analysis of health service-use data from 4
      consecutive years (1996-1999) of the Medical Expenditure Panel Survey, a
      nationally representative annual survey of the general population that is
      sponsored by the Agency for Healthcare Quality and Research, Rockville, Md.
      Subjects Patients aged 6 to 18 years who made 1 or more outpatient visits for the
      treatment of depression. MAIN OUTCOME MEASURES: Rate of treatment, mental health
      problems, psychotropic medication use, psychotherapy use, number of outpatient
      treatment visits, and type of provider. RESULTS: Across the 4 survey years, the
      mean annual rate of outpatient treatment for depression was 0.93 per 100
      individuals. The rate of treatment was especially low for African American
      individuals (0.23 per 100) and uninsured individuals (0.43 per 100).
      Approximately three quarters (79%) of treated children and adolescents received
      psychotherapy and more than half (56.9%) were prescribed antidepressant
      medications. The mean number of treatment visits for depression was 7.8 per year.
      As compared with children and adolescents with depression who were treated
      without antidepressants, those who received antidepressants were significantly
      more likely to have evidence of anhedonia, to live in large urban communities, to
      have parents who graduated from high school, and to have health insurance.
      CONCLUSIONS: The rate and pattern of treatment suggest that serious gaps exist in
      access to community outpatient treatment for children and adolescents with
      depression. At the same time, antidepressant medications are used far more
      commonly than would be expected on the basis of published treatment
      recommendations.

PMID- 14662557
TI  - Alterations in stress cortisol reactivity in depressed preschoolers relative to
      psychiatric and no-disorder comparison groups.
AB  - BACKGROUND: Despite the robust and widely replicated finding of elevated
      hypothalamic-pituitary-adrenal (HPA) axis reactivity in depressed adults, studies
      of depressed children have yielded ambiguous findings. Animal models of early
      depression and studies of children experiencing early psychosocial deprivation
      have suggested that alterations in HPA axis reactivity are evident in early
      "depressive-like" conditions. The current study is, to our knowledge, the first
      investigation of HPA axis reactivity in very young children with a clinical
      depressive syndrome for which content validity has been established. METHODS:
      Depressed, psychiatric, and no-disorder comparison children aged 3 through 5.6
      years were studied for HPA axis reactivity in response to experimental
      psychosocial stressors. The children were diagnosed using a developmentally
      appropriate, structured psychiatric interview. Salivary cortisol was obtained at
      3 time points during a laboratory assessment before and after stressors involving
      separation from the parent and frustrating tasks. RESULTS: Repeated measures of
      multivariate analysis of variance revealed a significant interaction between the
      diagnostic group and 2 cortisol percent change scores. Depressed preschoolers
      displayed a pattern of increasing cortisol levels throughout the assessment in
      response to both separation and frustration stressors. In contrast, both
      comparison groups showed decreasing cortisol levels in response to the separation
      stressor. All groups displayed increasing cortisol levels in response to
      frustrating tasks. Preschoolers with a presumptive melancholic depressive subtype
      displayed these alterations at a greater magnitude relative to comparison groups.
      CONCLUSIONS: To our knowledge, these findings are the first to demonstrate
      altered HPA axis reactivity in depressed preschoolers. These alterations are
      consistent with those described in depressed adults and in animal models of early
      depression. These findings provide evidence for possible continuity of HPA axis
      alterations in depressive disorders across the lifespan and are discussed in the
      context of prior studies of HPA axis reactivity in clinically depressed children
      and adolescents, suggesting that younger age and inpatient status are features
      associated with altered HPA axis reactivity.

PMID- 14662558
TI  - Genetic and environmental influences on substance initiation, use, and problem
      use in adolescents.
AB  - BACKGROUND: We conducted a sibling/twin/adoption study of substance initiation,
      use, and problem use, estimating the relative contribution of genetic and
      environmental influences on these phenotypes in adolescents. METHODS: The
      participants were 345 monozygotic twin pairs, 337 dizygotic twin pairs, 306
      biological sibling pairs, and 74 adoptive sibling pairs assessed by the Colorado
      Center for the Genetics and Treatment of Antisocial Drug Dependence, Denver and
      Boulder. The initiation, use, and problem use of tobacco, alcohol, marijuana, and
      other illicit drugs were assessed. Tetrachoric correlations were computed for
      each group, and univariate model-fitting analyses were conducted. RESULTS: There
      were moderate to substantial genetic influences, with the exception of alcohol
      use and any drug use, and modest to moderate shared environmental influences on
      substance initiation, use, and problem use. For alcohol and any drug,
      heritability was higher and the magnitude of shared environmental influences was
      lower for problem use than for initiation or use. Environmental influences shared
      only by twin pairs had a significant effect on tobacco initiation, alcohol use,
      and any drug use. For tobacco use, tobacco problem use, and marijuana initiation,
      heritability was higher and the magnitude of shared environmental influences was
      lower in female than in male adolescents. There was no evidence for sex-specific
      genetic or shared environmental influences on any variable. CONCLUSIONS: The
      moderate to substantial heritabilities found for adolescents in the present study
      are comparable to those found in twin studies of adult substance use and
      substance use disorders. The finding that problem use is more heritable than
      initiation and use is also consistent with the results of adult twin studies. The
      significance of environmental influences shared only by twin pairs on tobacco
      initiation, alcohol use, and any drug use suggests the influences of peers,
      accessibility of substances, and sibling interaction.

PMID- 14662559
TI  - Genetic and environmental effects on offspring alcoholism: new insights using an
      offspring-of-twins design.
AB  - CONTEXT: Although there is now considerable evidence that genetic effects play a
      critical role in the development of alcohol dependence (AD), theoretical and
      methodological limitations of this literature require caution in describing the
      etiology and development of this disorder. OBJECTIVE: To disentangle genetic and
      environmental effects on AD by means of the infrequently used, yet potentially
      powerful, offspring-of-twins design. DESIGN: Offspring of twins. PARTICIPANTS:
      Male monozygotic and dizygotic twins concordant or discordant for AD and control
      pairs from the Vietnam Era Twin Registry were assessed, as were the offspring of
      these twins and the mothers of these offspring. INTERVENTIONS: Structured
      psychiatric interviews. MAIN OUTCOME MEASURES: Participants' psychiatric, alcohol
      abuse (AA), and AD histories (DSM-IV). RESULTS: Offspring of monozygotic and
      dizygotic twins with a history of AD were significantly more likely to exhibit AA
      or AD than were offspring of nonalcoholic fathers. Offspring of an alcohol
      abusing monozygotic twin whose co-twin was AD were also more likely to exhibit AD
      than were offspring of nonalcoholic twins. In contrast, offspring of an
      unaffected (ie, no history of abuse or dependence) monozygotic twin whose co-twin
      was AD were no more likely to exhibit AA or AD than were offspring of
      nonalcoholic twins. CONCLUSIONS: These findings support the hypothesis that
      family environmental effects do make a difference in accounting for offspring
      outcomes, in particular, that a low-risk environment (ie, the absence of parental
      alcoholism) can moderate the impact of high genetic risk regarding offspring for
      the development of alcohol-use disorders.

PMID- 14662562
TI  - Predicting neonatal brain injury: are we there yet?

PMID- 14662563
TI  - The case for evidence-based toilet training.

PMID- 14662564
TI  - Norms of "culture" in a culture of norms.

PMID- 14662565
TI  - Questioning dogma: is this test needed?

PMID- 14662566
TI  - On difference.

PMID- 14662567
TI  - Measurement of urinary S100B protein concentrations for the early identification
      of brain damage in asphyxiated full-term infants.
AB  - BACKGROUND: Perinatal asphyxia is a major cause of mortality and morbidity. To
      date there are no reliable methods to detect which infants will develop brain
      damage after asphyxia insult. We investigated whether measurements of urine
      levels of S100B in asphyxiated full-term newborns may be a useful tool for early
      detection of postasphyxia brain damage. METHODS: A prospective study of 38
      infants with perinatal asphyxia and 96 control subjects, recruited at 3 tertiary
      departments of neonatology between April 1, 1999, and July 31, 2001. Routine
      laboratory variables, neurologic patterns, and urine concentrations of S100B
      protein were determined at 4 predetermined time points (first urination and 12,
      24, and 72 hours after birth). The concentrations of S100B protein in urine were
      measured using an immunoluminometric assay. The results were correlated with the
      presence or absence of neurologic abnormalities at age 12 months. RESULTS: S100B
      protein levels were significantly higher in samples collected at all monitoring
      times from new-borns with abnormal neurologic findings on follow-up (first
      urination, 1.92 +/- 0.33 micro g/L; 12 hours, 2.78 +/- 1.71 micro g/L; 24 hours,
      4.75 +/- 4.08 micro g/L; 72 hours, 5.93 +/- 1.63 micro g/L) than in samples from
      those without (first urination, 0.24 +/- 0.06 micro g/L; 12 hours, 0.13 +/- 0.06
      micro g/L; 24 hours, 0.21 +/- 0.07 micro g/L; 72 hours, 0.12 +/- 0.04 micro g/L)
      or from healthy infants (first urination, 0.11 +/- 0.01 micro g/L; 12 hours, 0.12
      +/- 0.03 micro g/L; 24 hours, 0.12 +/- 0.02 micro g/L; 72 hours, 0.12 +/- 0.02
      micro g/L) (P<.001 for all). An S100B concentration cutoff of 0.28 micro g/L at
      first urination had a sensitivity of 100% and a specificity of 87.3% for
      predicting the development of abnormal neurologic findings on follow-up. The
      sensitivity and specificity of measurements obtained between 12 and 72 hours were
      up to 100% and 98.2%, respectively. CONCLUSION: Longitudinal S100B protein
      measurements in urine soon after birth are a useful tool to identify which
      asphyxiated infants are at risk of long-term neurologic sequelae.

PMID- 14662568
TI  - Use of the Pediatric Symptom Checklist in a low-income, Mexican American
      population.
AB  - OBJECTIVE: To evaluate the usefulness of the Pediatric Symptom Checklist (PSC) in
      identifying behavioral problems in low-income, Mexican American children. DESIGN:
      A cross-sectional study design was used to examine the PSC as a screening test,
      with the Child Behavior Checklist (CBCL) as the criterion standard. SETTING: The
      study was conducted at a health center in a diverse low-income community.
      Patients Eligible patients were children and adolescents, 4 to 16 years of age,
      who were seen for nonemergent, well-child care. Of 253 eligible children during a
      9-month study period, 210 agreed to participate in the study. There was a 100%
      completion rate of the questionnaires. The average age of the children was 7.5
      years, and 45% were female. Ninety-five percent of patients were of Hispanic
      descent (Mexican American); 86% of families spoke only Spanish. Socioeconomic
      status was low (more than three fourths of families earned <$20 000 annually).
      RESULTS: The CBCL Total scale determined that 27 (13%) of the children had
      clinical levels of behavioral problems. With a cutoff score of 24, the PSC
      screened 2 (1%) of the 210 children as positive for behavioral problems. Using
      the CBCL as the criterion standard, the PSC sensitivity was 7.4%, and the
      specificity was 100%. Receiver operator characteristic analysis determined that a
      PSC cutoff score of 12 most correctly classified children with and without
      behavioral problems (sensitivity, 0.74; specificity, 0.94). CONCLUSIONS: When
      using the PSC, a new cutoff score of 12 for clinical significance should be
      considered if screening low-income, Mexican American children for behavioral
      problems. Additional study is indicated to determine the causes of the PSC's
      apparently lower sensitivity in Mexican American populations.

PMID- 14662569
TI  - Randomized clinical trial of docusate, triethanolamine polypeptide, and
      irrigation in cerumen removal in children.
AB  - BACKGROUND: Cerumen obstructing visualization of the tympanic membrane in
      children is a common and frustrating problem. Docusate sodium, triethanolamine
      polypeptide, and saline were compared to determine their effectiveness in
      relieving cerumen obstruction in children. METHODS: A randomized, controlled,
      double-blind trial was performed on pediatric patients aged 6 months through 5
      years with cerumen obstruction. The enrolling physician determined whether the
      cerumen completely or partially obstructed visualization of the tympanic
      membrane. One milliliter of docusate sodium, triethanolamine polypeptide, or
      normal saline as control was placed into the patient's ear canal. If the tympanic
      membrane was not completely visualized after 15 minutes, the ear was irrigated
      with 50 mL of tepid water. Irrigation was repeated a second time if needed. The
      main outcome was the proportion of tympanic membranes that were completely
      visualized after cerumeno-eblytic agents or control saline, alone or with
      irrigation if needed. RESULTS: Of 92 patients enrolled, 34 received docusate
      sodium; 30, triethanolamine polypeptide; and 28, saline. Mean +/- SD patient age
      was 34.7 +/- 18.1 months, and 50 (54%) of the patients were girls. Groups were
      similar in age, race, sex, ear enrolled, wax consistency, and degree of
      obstruction. There was no significant difference in the proportion of tympanic
      membranes completely visualized after treatment with docusate (18/34; 53%),
      triethanolamine polypeptide (13/30; 43%), or saline (19/28; 68%) (P =.17).
      CONCLUSION: Application of docusate sodium or triethanolamine polypeptide did not
      significantly improve the proportion of tympanic membranes that were completely
      visualized vs application of the saline control.

PMID- 14662570
TI  - Review of a randomized trial comparing 2 cerumenolytic agents.

PMID- 14662571
TI  - Allergic disease at the age of 7 years after pertussis vaccination in infancy:
      results from the follow-up of a randomized controlled trial of 3 vaccines.
AB  - OBJECTIVE: To prospectively assess sensitization rates and the development of
      allergic diseases in a follow-up of a randomized controlled pertussis vaccine
      trial. SETTING: Two-month-old infants were the subject of this double-blind study
      in 1992 in a collaboration between the Pediatric Clinic and the Primary Care
      Centers in Linkoping. PATIENTS AND INTERVENTION: Allergic diseases were evaluated
      in 667 children, who were randomized to 1 of 4 vaccine groups: a 2-component, a 5
      component, or a whole cell pertussis vaccine (all of which were administered with
      the diphtheria and tetanus toxoids vaccine) and the diphtheria and tetanus
      toxoids vaccine alone. Allergy development was assessed by questionnaires (n =
      667) and skin prick tests (n = 538) at the age of 7 years. MAIN OUTCOME MEASURES:
      Allergic diseases and skin prick test results at the age of 7 years. RESULTS: The
      cumulative incidence of allergic diseases was 34.9%, and was similar in the 4
      groups (33.3%-37.3%, P =.89), even after adjusting for family history, sex, pets,
      dampness, environmental smoking at home, and other living conditions. Positive
      skin prick test results were more prevalent, however, after vaccination with the
      2-component acellular vaccine (19.4%) than in the other 3 groups (11.1%-13.5%,
      adjusted for confounding factors, P =.01). Furthermore, allergic
      rhinoconjunctivitis was more common in children who were initially immunized with
      the 2-component pertussis vaccine and received a booster dose with an acellular
      vaccine compared with those who received no booster vaccination (relative risk,
      3.6; 95% confidence interval, 1.1-12.0). CONCLUSION: Pertussis vaccination in
      infancy with any of these vaccines was not associated with allergic
      manifestations at the age of 7 years, apart from a higher prevalence of positive
      skin prick test results after an experimental 2-component vaccine, which is no
      longer in use.

PMID- 14662572
TI  - Children who hide while defecating before they have completed toilet training: a
      prospective study.
AB  - OBJECTIVE: To examine the incidence and age at onset of hiding while defecating
      in children before they have been toilet trained and its association with
      difficulties in toilet training. DESIGN: Prospective study. SETTING: Suburban
      private pediatric practice. Subjects Three hundred seventy-eight children aged 17
      to 19 months. METHODS: Children were followed up by telephone interviews with the
      parents every 2 to 3 months until the child completed daytime toilet training.
      Children who were described at any follow-up telephone call as always or almost
      always hiding when defecating prior to completing toilet training were defined as
      the hiding group. The remainder of the children, who were described as never
      hiding or only sometimes hiding, was defined as the nonhiding group. RESULTS: Two
      hundred sixty-three children (69.6%) met the criteria for the hiding group. The
      median age at initiation of hiding for the group was 22 months. Thirty-eight
      began hiding before toilet training was initiated and 64 started hiding after
      intensive toilet training had begun. The nonhiders (115 [30.4%]) were
      significantly less likely to have stool toileting refusal, frequent constipation,
      or stool withholding. They also completed toilet training at an earlier age than
      the hiders (34.5 +/- 5.9 months vs 38.1 +/- 5.9 months; P<.001). CONCLUSIONS: The
      behavior of hiding while defecating before completion of toilet training is
      associated with stool toileting refusal, constipation, and stool withholding.
      These behaviors may make toilet training more difficult.

PMID- 14662573
TI  - Stool toileting refusal: a prospective intervention targeting parental behavior.
AB  - OBJECTIVE: To evaluate the effect of an intervention targeting parental behavior
      on stool toileting refusal. METHODS: This study population comprised 406 children
      aged 17 through 19 months from a single suburban private practice. Children were
      randomly assigned to receive 1 of 2 written toilet-training instructions. Both
      groups were advised to use a child-oriented approach to toilet training. In
      addition, those in the intervention group were requested to avoid using negative
      terms for feces and, before training began, to praise the children when they
      defecated in the diaper. Follow-up telephone calls were made every 2 to 3 months,
      and 381 children were followed up until they developed stool toileting refusal or
      completed daytime toilet training. RESULTS: The incidence of stool toileting
      refusal was 23% in the control group and 26% in the intervention group (P>.10).
      The mean +/- SD duration was 5.2 +/- 4.9 months in the intervention group vs 7.6
      +/- 4.9 in the control group (P =.04). Children with stool toileting refusal in
      the intervention group trained at 40.0 +/- 6.4 months vs 43.0 +/- 6.5 months in
      the control group (P =.04). CONCLUSIONS: The intervention did not decrease the
      incidence of stool toileting refusal but did shorten its duration, leading to
      earlier completion of toilet training. This should help to ameliorate some of the
      negative consequences of stool toileting refusal.

PMID- 14662575
TI  - Impact of environmental tobacco smoke on children with sickle cell disease.
AB  - BACKGROUND: Parallels between the biological effects of exposure to environmental
      tobacco smoke (ETS) on nonsmokers and the pathophysiology of sickle cell disease
      (SCD) suggest that complications of SCD could be exacerbated by ETS exposure.
      OBJECTIVE: To determine whether children with SCD who are exposed to ETS at home
      have more sickle cell crises than do those who live in nonsmoking households.
      DESIGN: A retrospective cohort study in which ETS exposure was measured by using
      a survey of caretakers and patients. SETTING: A university-based pediatric sickle
      cell center. PARTICIPANTS: Fifty-two of 66 eligible children aged 2 to 18 years
      with SCD. OUTCOME MEASURES: The number of sickle cell vaso-occlusive crises
      requiring hospitalization per patient during the 2-year study (inpatient sickle
      cell crises). Total hospital days and hospital costs were secondary outcome
      measures. RESULTS: Patients exposed to ETS had more inpatient sickle cell crises
      than did unexposed patients (mean +/- SD, 3.7 +/- 5.7 vs 1.7 +/- 3.5; P =.02),
      and this association retained significance after adjustment for important
      covariates (risk ratio, 1.9; 95% confidence interval, 1.3-2.7). Hospital costs
      were greater in the exposed group than in the unexposed group (mean +/- SD,
      21,671 US dollars +/- 41,809 US dollars vs 9705 US dollars +/- 19 146 US dollars;
      effect estimate, 11.4; 95% confidence interval, 1.0-129.5). CONCLUSIONS: Children
      with SCD who are exposed to ETS have a higher risk of sickle cell crises
      requiring hospitalization than do those not exposed, independent of other factors
      known to increase the frequency of sickle cell crises. Decreasing the exposure of
      these children to ETS could reduce morbidity and may provide cost savings.

PMID- 14662576
TI  - Predicting adoption of home smoking restriction by inner-city black smokers.
AB  - OBJECTIVE: To identify predictors of future adoption of home smoking restriction
      (HSR), given that 40% of inner-city smokers report current HSR. DESIGN: Secondary
      analysis of data on smokers enrolled in a double-blind, placebo-controlled,
      randomized trial of bupropion hydrochloride for smoking cessation. SETTING:
      Community health center in Kansas City, Kan, from August 1, 2000, to December 31,
      2001. PARTICIPANTS: Six hundred eligible black smokers, at least 18 years old,
      who smoked at least 10 cigarettes per day and were interested in quitting within
      the next 30 days. Enrollment was limited to 1 smoker per household. MAIN OUTCOME
      MEASURES: Adoption of HSR by 6 months by those who did not have it at baseline.
      Result Baseline HSR was reported by 36% of all smokers. Of 383 smokers without
      baseline HSR, 311 smokers had complete baseline and 6-month data. Thirty-seven
      percent of households without HSR at baseline had adopted HSR by 6 months.
      Adoption was associated with a nonsmoking adult or children in the home, progress
      in stage of change, and smoking cessation. Odds of adopting HSR increased with
      progress in stage of change (odds ratio [OR], 4.20), baseline preparatory stage
      of change (OR, 3.28), and having a nonsmoking partner (OR, 2.35) or children (OR,
      1.75) in the home. CONCLUSIONS: A smoker's motivation to quit and the presence in
      the home of a nonsmoking adult or of children predict adoption of HSR by inner
      city black smokers. Therefore, health professionals should motivate the smoker
      toward HSR and the nonsmoking partner toward advocating home smoking bans,
      thereby eliminating environmental tobacco smoke in the home.

PMID- 14662577
TI  - Decreased quality of life associated with obesity in school-aged children.
AB  - OBJECTIVES: To examine the association between health-related quality of life and
      body mass index (BMI) in preadolescent school-aged children and to provide the
      possible risk factors among participant characteristics, BMI status, and health
      related quality of life. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      analysis of 371 (50% female; 32% minority) children from a community-based sample
      of 8- to 11-year-olds participating in an ongoing cohort study, excluding those
      who had sleep apnea or who were born prematurely. Using BMI percentiles for age
      and sex, 17.5% of the children were considered overweight (BMI > or =95th
      percentile), 12.4% were at risk for overweight (BMI 85th-94th percentile), 8.1%
      were relatively underweight (BMI <20th percentile), and the remaining 62.0% were
      of normal weight (BMI 20th-84th percentile). MAIN OUTCOME MEASURES: Health
      related quality-of-life scores as determined by the Child Health Questionnaire
      Parent Form 50, dichotomized into the bottom quartile or decile. RESULTS: After
      adjustment for covariates (host factors and health status measurements),
      overweight children compared with normal weight children scored lower on the
      Psychosocial Health Summary (odds ratio [OR], 2.0; 95% confidence interval [CI],
      1.1-3.6) and on subscales measuring self-esteem (OR, 3.5; 95% CI, 1.9-6.3),
      physical functioning (OR, 2.8; 95% CI, 1.7-6.8), and effect on the parent's
      emotional well-being (OR, 2.0; 95% CI, 1.1-3.6). Compared with the normal weight
      group, children who are at risk for overweight scored significantly lower for
      physical functioning. CONCLUSION: Overweight children have an increased odds of
      low scores for several health-related quality-of-life domains, suggesting the
      importance in considering such dimensions in programs aimed at further
      understanding obesity in children.

PMID- 14662578
TI  - Predictors and tracking of body mass index from adolescence into adulthood:
      follow-up of 18 to 20 years in the Oslo Youth Study.
AB  - OBJECTIVES: To examine tracking of body mass index (BMI) (weight in kilograms
      divided by the square of height in meters) from age 15 to 33 years, to examine
      the effect of adolescent and adult health-related behavior and parents' BMI and
      education on adult BMI; and to examine changes in lifestyle factors as predictors
      of adult overweight and obesity. METHODS: A longitudinal study with 18 to 20
      years of follow-up in a cohort from Oslo, Norway (N = 485); mean age was 15 years
      at baseline. Weight, height, physical fitness, leisure time physical activity
      (LTPA), smoking, and education were assessed at baseline and follow-up. Parents'
      height, weight, and education were assessed at baseline. RESULTS: Tracking of BMI
      from age 15 to 33 years was high (r = 0.54). Adolescent BMI, father's BMI, the
      subject's own LTPA, adult smoking, and sex explained 44.1% of the variation in
      adult BMI. The odds ratio (95% confidence interval) of having a BMI of 25 or more
      as an adult was 0.07 (0.03-0.14) for lowest vs highest quartile of adolescent
      BMI. The corresponding odds ratio of having a BMI of 30 or more was 0.02 (0.002
      0.14). Those who increased their LTPA level between adolescence and adulthood had
      a lower risk of adult overweight than those with a stable low LTPA level.
      CONCLUSIONS: Tracking of BMI from adolescence into adulthood was substantial.
      Changes in LTPA between adolescence and adulthood predicted the risk of adult
      overweight, suggesting that the foundation for adult body weight is laid during
      adolescence. Implications of this would be to emphasize physical activity among
      youths.

PMID- 14662579
TI  - The incidence of pain in children with severe cognitive impairments.
AB  - BACKGROUND: Children with severe cognitive impairments are believed to suffer
      pain frequently. OBJECTIVE: To document the frequency, duration, and intensity of
      pain experienced by children with severe cognitive impairments. DESIGN: Cohort
      study using surveys during 1 year. SETTING: Tertiary-care pediatric center for 3
      provinces in eastern Canada. PARTICIPANTS: Caregivers of 94 children and
      adolescents with moderate to profound mental retardation, aged 3 to 18 years
      (mean age, 10.1 years [SD, 4.3 years]). Forty-four children had cerebral palsy
      and 59 had a seizure disorder; 83 lived with family, and 11 in group homes. Main
      Outcome Measure Caregivers completed 4 semistructured telephone surveys,
      reporting the cause, duration (in minutes), and intensity (on a scale of 0-10) of
      children's pain during the previous week. RESULTS: A total of 406 episodes of
      pain occurred. During a 4-week period, 73 children (78%) experienced pain at
      least once, and 58 (62%) had nonaccidental pain. Accidental pain was most
      frequent (n = 28 [30%]), followed by gastrointestinal tract (n = 21 [22%]),
      infection (n = 19 [20%]), and musculoskeletal (n = 18 [19%]) pain. Each week, 33
      to 49 children (35%-52%) had pain. Mean pain duration was longer than 9 hours per
      week (SD, 1.7-2.4 hours). Mean intensity was 6.1 (SD, 2.2) for nonaccidental pain
      and 3.8 (SD, 2.1) for accidental pain. Children with the fewest abilities had
      more nonaccidental pain (F4,89 = 3.7; P =.007), and children with greater motor
      abilities had more accidental pain (F4,89 = 2.8; P =.03). Pain did not vary with
      demographic characteristics. CONCLUSIONS: Children with severe cognitive
      impairments experience pain frequently, mostly not due to accidental injury.
      Children with the fewest abilities experience the most pain.

PMID- 14662580
TI  - Self-assessment of tuberculosis infection risk by urban adolescents.
AB  - OBJECTIVE: To examine self-reported risks for tuberculosis (TB) infection
      relative to recalled receipt of TB risk assessments and skin testing in a cohort
      of urban adolescents. DESIGN, SETTING, AND PARTICIPANTS: Survey of ninth graders
      and their parents from 3 inner-city public high schools. Students and parents
      were asked about TB infection risk factors, frequency of routine health
      maintenance visits, TB risk assessments, and TB skin testing. Students were
      surveyed in schools and asked to take home surveys for their parents to complete.
      RESULTS: Of 578 students (95.4% response rate), 436 (75.4%) claimed at least 1 TB
      infection risk factor. Although 468 (81.0%) of the students reported having a
      regular checkup within the past year, only 128 (22.1%) recalled being asked TB
      risk assessment questions and only 231 (40.0%) recalled undergoing skin testing
      during the previous year. Parent response rates were low (n = 207; 34.2% response
      rate), and parents of students attending bilingual classes were overrepresented
      among responders. There were no significant relationships between self-indicating
      a risk for TB infection and self-recollection of having undergone TB screening,
      having had a tuberculin skin test placed, or having had a regular checkup, with
      the exception that students who responded that they lived with a tuberculin skin
      test-positive person were 38% less likely to recall having had a tuberculin skin
      test themselves (n = 21; 95% confidence interval, 24%-50%). The level of
      agreement between student and parent responses in the 207 survey pairs available
      for analysis ranged from poor to good (kappa = 0.07-0.61) on individual
      questions. CONCLUSIONS: These observations suggest that most at-risk adolescents
      in this city are not being adequately screened for TB infection. Programs to
      improve health care provider acceptance of targeted testing principles or to
      reengage in school-based screening of students with certain risk factors seem
      necessary.

PMID- 14662581
TI  - Effect of orange and apple juices on iron absorption in children.
AB  - OBJECTIVE: To measure iron absorption in children from meals containing apple
      juice or orange juice so as to determine if iron absorption will be greater with
      orange juice because of its higher ascorbic acid content than apple juice, a
      noncitrus fruit juice that US children reportedly prefer. DESIGN: On 2 successive
      days, children consumed identical meals that included apple juice on one day and
      orange juice on the other, in random order. The meals were labeled with iron-57
      on one day and iron-58 on the other. Iron absorption was measured from red blood
      cell incorporation of the iron stable isotopes 14 days later. SETTING: Nutrition
      research institute in a major metropolitan medical center. PATIENTS: A total of
      25 healthy children, 3 to 6 years of age, were recruited, of whom 21 (11 male and
      10 female) completed the study. Intervention Identical meals served with orange
      juice and apple juice were given on consecutive days, in a balanced randomized
      design. MAIN OUTCOME MEASURES: Iron absorption measured by established stable
      isotope methods. RESULTS: Median iron absorption from the meal ingested with
      apple juice was 7.17% (mean +/- SD, 9.48% +/- 9.68%). Median iron absorption from
      the meal ingested with orange juice was 7.78% (9.80% +/- 6.66%; P =.44). Iron
      absorption from the meal that included apple juice was significantly correlated
      with serum ferritin concentration (P =.02); iron absorption from the meal that
      included orange juice tended to correlate with serum transferrin receptor
      concentration (P =.051). CONCLUSIONS: As children absorb iron well from a meal
      that includes either orange or apple juice, a preference for apple juice does not
      pose a concern with regard to the prospect of iron-deficiency anemia, which
      remains a significant health problem in the United States.

PMID- 14662582
TI  - Follow-up urine cultures and fever in children with urinary tract infection.
AB  - BACKGROUND: The American Academy of Pediatrics practice parameter for urinary
      tract infection suggests a repeat urine culture if the expected clinical response
      is not achieved within the first 48 hours of therapy. The utility of repeat urine
      cultures and clinical significance of fever at 48 hours is unclear. OBJECTIVES:
      To determine the frequency of positive repeat urine cultures in children admitted
      to the hospital with urinary tract infection, and to describe the fever curves of
      children admitted to the hospital with urinary tract infection. DESIGN AND
      METHODS: We reviewed all cases of urinary tract infection in children 18 years
      and younger who were admitted during a 5-year period to Children's Hospital of
      Wisconsin (Milwaukee). We recorded temperatures from hospital admission to
      discharge, age, sex, initial and follow-up culture results, antibiotics received,
      imaging performed, and medical history. RESULTS: Urinary tract infection was
      identified in 364 patients, and 291 (79.9%) had follow-up urine cultures. None
      were positive. Follow-up cultures produced 21,388.50 US dollars in patient
      charges. Fever lasted beyond 48 hours in 32% of patients. Older children were
      more likely to have fever beyond 48 hours. CONCLUSIONS: Follow-up urine cultures
      were of no utility in children hospitalized for urinary tract infection,
      including those with fever lasting beyond 48 hours or those with an underlying
      urologic disease. Fever beyond 48 hours is common and should not be used as a
      criterion for obtaining a repeat urine culture. These conclusions are valid for
      children with vesicoureteral reflux. Such an approach would result in significant
      cost savings.

PMID- 14662583
TI  - Reassessing Reye syndrome.

PMID- 14662584
TI  - Acknowledging past contributions.

PMID- 14662586
TI  - Revised indications for the treatment of retinopathy of prematurity: results of
      the early treatment for retinopathy of prematurity randomized trial.
AB  - OBJECTIVE: To determine whether earlier treatment using ablation of the avascular
      retina in high-risk prethreshold retinopathy of prematurity (ROP) results in
      improved grating visual acuity and retinal structural outcomes compared with
      conventional treatment. METHODS: Infants with bilateral high-risk prethreshold
      ROP (n = 317) had one eye randomized to early treatment with the fellow eye
      managed conventionally (control eye). In asymmetric cases (n = 84), the eye with
      high-risk prethreshold ROP was randomized to early treatment or conventional
      management. High risk was determined using a model based on the Multicenter Trial
      of Cryotherapy for Retinopathy of Prematurity natural history cohort. At a
      corrected age of 9 months, visual acuity was assessed by masked testers using the
      Teller acuity card procedure. At corrected ages of 6 and 9 months, eyes were
      examined for structural outcome. Outcomes for the 2 treatment groups of eyes were
      compared using chi2 analysis, combining data for bilateral and asymmetric cases.
      RESULTS: Grating acuity results showed a reduction in unfavorable visual acuity
      outcomes with earlier treatment, from 19.5% to 14.5% (P =.01). Unfavorable
      structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. Further
      analysis supported retinal ablative therapy for eyes with type 1 ROP, defined as
      zone I, any stage ROP with plus disease (a degree of dilation and tortuosity of
      the posterior retinal blood vessels meeting or exceeding that of a standard
      photograph); zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3
      ROP with plus disease. The analysis supported a wait-and-watch approach to type 2
      ROP, defined as zone I, stage 1 or 2 ROP without plus disease or zone II, stage 3
      ROP without plus disease. These eyes should be considered for treatment only if
      they progress to type 1 or threshold ROP. CONCLUSIONS: Early treatment of high
      risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically
      important degree. Additional analyses led to modified recommendations for the use
      of peripheral retinal ablation in eyes with ROP. Long-term follow-up is being
      conducted to learn whether the benefits noted in the first year after birth will
      persist into childhood.

PMID- 14662587
TI  - Risk analysis of prethreshold retinopathy of prematurity.
AB  - OBJECTIVE: To present a new multifactorial algorithm to integrate important risk
      factors for unfavorable retinal outcome in eyes that reached prethreshold
      retinopathy of prematurity (ROP) in the Cryotherapy for Retinopathy of
      Prematurity (CRYO-ROP) study. A computerized risk model (RM-ROP2) was developed
      from this algorithm to identify high-risk prethreshold eyes for enrollment in the
      Early Treatment for Retinopathy of Prematurity randomized trial. METHODS: Data
      were analyzed from 613 eyes (1 eye per infant) in the natural history cohort of
      the Multicenter Trial for Cryotherapy for Retinopathy of Prematurity. These eyes
      were selected from infants in whom 1 or both eyes progressed to prethreshold ROP.
      Eyes that progressed to threshold ROP and were randomized to cryotherapy were
      excluded from this study, but control eyes that reached threshold ROP were
      included. The course of ROP for 1 prethreshold eye for each infant was tracked
      until the evaluation of its structural outcome at 3 months' postterm. Tables
      present structural outcome by selected risk characteristics. A multiple logistic
      risk model is used to summarize the combined effect of all of these known
      prognostic risk factors as they relate to structural outcome. RESULTS: Eyes were
      classified by predicted outcome into 10 risk categories, lowest to highest. Both
      the observed and predicted outcomes in each category showed an increasingly
      unfavorable outcome when viewed from lowest to highest risk. Prethreshold ROP
      eyes were then divided into 2 groups, high-risk, eyes (risk, 0.15-1.0) and low
      risk eyes (risk, <0.15). High-risk eyes had an unfavorable outcome of 36% at 3
      months' postterm; whereas, only 5% of the low-risk eyes had an unfavorable
      outcome. CONCLUSION: The model effectively identifies prethreshold ROP eyes that
      have a relatively high risk and eyes that have a lower risk of an unfavorable
      structural outcome at 3 months.

PMID- 14662588
TI  - Long-term acyclovir use to prevent recurrent ocular herpes simplex virus
      infection.
AB  - OBJECTIVE: To evaluate the effectiveness of more than 12 months of oral acyclovir
      therapy in reducing recurrences of ocular herpes simplex virus. METHODS: We
      retrospectively compared ocular herpes simplex virus recurrence in 2 groups of
      patients. In group 1, patients used oral acyclovir for at least 12 months and
      then discontinued the treatment. In group 2, patients received the treatment for
      at least 18 months. We compared recurrences when both groups were using acyclovir
      (period 1) and when only group 2 was receiving the drug (period 2). Statistical
      analysis was performed with the t test, chi2 test, and Kaplan-Meier method.
      RESULTS: Group 1 had 18 patients and a mean +/- SD follow-up of 45.2 +/- 22.2
      months. Group 2 had 22 patients and a mean +/- SD follow-up of 42.4 +/- 30.2
      months. Six patients (33%) in group 1 and 4 patients (18%) in group 2 had
      recurrence in period 1 (P =.3). In period 2, 14 patients (78%) in group 1 and 8
      patients (36%) in group 2 had recurrence (P =.01). Mean +/- SD recurrence-free
      survival in period 2 was 15.3 +/- 5.5 months in group 1 and 37.3 +/- 6.3 months
      in group 2 (P =.001). CONCLUSIONS: Long-term oral acyclovir use seems to remain
      effective in decreasing the number of ocular herpes simplex virus recurrences
      beyond 12 months.

PMID- 14662589
TI  - Detection of early visual field loss in glaucoma using frequency-doubling
      perimetry and short-wavelength automated perimetry.
AB  - OBJECTIVE: To investigate whether frequency-doubling perimetry (FDP) predicts
      future visual field loss with achromatic automated perimetry (AAP), just as it
      may be predicted with short-wavelength automated perimetry (SWAP). METHODS: We
      recruited 62 patients selectively from an urban glaucoma practice. At the
      commencement of the study, each patient had ocular hypertension with normal
      visual fields on AAP. Baseline SWAP and FDP were performed to determine whether
      underlying earlier visual field loss was present. Patients were then followed up
      prospectively for 3 years with annual AAP, SWAP, and FDP. Main Outcome Measure
      The development of visual field loss on AAP. RESULTS: Nine subjects had abnormal
      SWAP findings and 10 had abnormal FDP findings. At the conclusion of the study,
      field loss on AAP developed in 5, all of whom had preexisting abnormal SWAP and
      FDP results. No AAP visual field loss developed in patients with a normal SWAP or
      FDP. The rate of development of visual field loss on AAP was therefore
      significantly greater for those with abnormal SWAP (chi21 = 40.83; P<.001) and
      abnormal FDP findings (chi21 = 32.76; P<.001) than for those with normal SWAP and
      FDP findings. CONCLUSION: In the same way that SWAP may predict AAP visual field
      loss, FDP may also detect field loss earlier than AAP.

PMID- 14662590
TI  - Ocular hemodynamics and glaucoma prognosis: a color Doppler imaging study.
AB  - OBJECTIVE: To evaluate the effect of optic nerve circulation, using color Doppler
      imaging (CDI), on the progression of visual field damage in primary open-angle
      glaucoma. METHODS: The relationship between the results of retrobulbar CDI,
      performed shortly after the diagnosis of primary open-angle glaucoma, and the
      progression of visual field loss for 7 years was evaluated in 44 glaucoma
      patients. Color Doppler imaging variables in patients with a stable and
      deteriorating clinical course were compared, and the pattern of increasing risk
      for different CDI values was analyzed using an additive logistic model. Based on
      this nonparametric analysis, we arrived at a discriminant CDI value identifying
      glaucoma patients with a poor prognosis. On the basis of the discriminant value,
      patients were divided into 2 groups, and the odds ratio of visual field loss for
      each group was then estimated. RESULTS: Patients with a stable visual field had a
      higher diastolic velocity and a lower resistivity index in the ophthalmic artery
      (P<.001 for both) compared with those with a deteriorating visual field during
      the study. The odds of visual field deterioration in patients with an ophthalmic
      artery resistivity index of 0.78 or higher was about 6 times that of patients
      with an ophthalmic artery resistivity index lower than 0.78. CONCLUSION: Color
      Doppler imaging variables of the ophthalmic artery correlate with the risk of
      visual field deterioration in patients with primary open-angle glaucoma.

PMID- 14662591
TI  - Ocular-hypertensive and anti-inflammatory response to rimexolone therapy in
      children.
AB  - OBJECTIVE: To compare the ocular-hypertensive and anti-inflammatory response to
      rimexolone (116-hydroxy-16alphafluoro-6alphamethylpresdnisolone) and
      fluorometholone (21-deoxy-9alphafluoro-6alphamethylprednisolone) therapy in
      children's eyes. METHODS: With parental consent, children who underwent surgical
      procedures for bilateral symmetric strabismus from January 18, 2000, through
      November 16, 2001, were recruited. One eye was randomized to receive topical 1%
      rimexolone while the contralateral eye received topical 0.1% fluorometholone, 4
      times daily for 4 weeks. MAIN OUTCOME MEASURES: Intraocular pressures and anti
      inflammatory responses were the main outcome measures and were serially measured
      postoperatively for 8 weeks. RESULTS: Fifty-four children, aged from 4 to 8 years
      (mean [SD] age, 5.33 [1.26] years), participated in the study. Intraocular
      pressure increased significantly in both treatment groups compared with the
      preoperative values (P<.001). The mean (SD) peak intraocular pressure was
      significantly higher in the rimexolone-treated group, 19.7 (6.1) vs 17.6 (4.6) mm
      Hg (P<.001). Similarly, the mean (SD) net increase in intraocular pressure
      (P<.001), was also higher in the rimexolone-treated eyes, 5.9 (4.4) vs 3.9 (4.1)
      mm Hg (P<.001). In addition, a greater percentage of the rimexolone-treated
      patients had no conjunctival erythema on days 13 (11.1% vs 0.0%) and 20 (88.9% vs
      55.6%) (P =.03). CONCLUSIONS: Rimexolone seems to be a more effective anti
      inflammatory agent than fluorometholone. However, unlike adults, the ocular
      hypertensive effect in children treated with rimexolone was higher. It would be
      desirable to monitor the intraocular pressure regularly when rimexolone therapy
      is used in children.

PMID- 14662592
TI  - Theoretical and measured pseudophakic accommodation after implantation of a new
      accommodative posterior chamber intraocular lens.
AB  - OBJECTIVE: To analyze different techniques of measuring accommodation after
      implantation of a new accommodative posterior chamber intraocular lens (PCIOL).
      METHODS: In this comparative, nonrandomized interventional study, we analyzed 15
      eyes of 15 patients (aged 44-84 years) at 6 months after cataract surgery and
      PCIOL implantation (Akkommodative 1CU; HumanOptics AG, Erlangen, Germany) and
      compared these results with those of an age-matched control group (n = 15). We
      used the following methods to measure accommodation: dynamic measurement with
      objective (videorefractometry [PowerRefractor; PlusOptix, Erlangen] and streak
      retinoscopy) and subjective (subjective near point [push-up test and
      accommodometer] and defocusing) techniques, as well as static measurement of the
      change in anterior chamber depth (ACD) using the IOLMaster (Zeiss, Jena, Germany)
      after pharmacological stimulation using 2% pilocarpine eye drops. MAIN OUTCOME
      MEASURES: Theoretical accommodation calculated from the forward shift of the lens
      optics (decrease of ACD) using paraxial geometrical optics and measured
      accommodation amplitude. RESULTS: Accommodation amplitude (mean +/- SD; range;
      median) results after 6 months in the study and control groups were as follows:
      1.00 +/- 0.44; 0.75-2.13; 1 diopter (D); and 0.35 +/- 0.26; 0.10-0.65; 0.25 D,
      respectively, using the PowerRefractor; 0.99 +/- 0.48; 0.13-2.00; 0.88 D; and
      0.24 +/- 0.21; -0.13-0.75; 0.25 D, respectively, using retinoscopy; 1.6 +/- 0.55;
      0.50-2.56; 1.7 D; and 0.42 +/- 0.25; 0.00-0.75; 0.50 D, respectively, using
      subjective near point; and 1.46 +/- 0.53; 1.00-2.50; 1.75 D; and 0.55 +/- 0.33;
      0.25-0.87; 0.50 D, respectively, using defocusing. Anterior chamber depth
      decreased in the study and control groups as follows: 0.78 +/- 0.12; 0.49-1.91;
      0.65 mm; and 0.16 +/- 0.09; 0.00-0.34; 0.18 mm, respectively, after applying 2%
      pilocarpine eyedrops, indicating an accommodation of 1.16 +/- 0.22; 0.72-1.88;
      1.05 D vs 0.22 +/- 0.13; 0.00-0.47; 0.23 D (P =.001). CONCLUSIONS: Accommodation
      after implantation of a presumably accommodative PCIOL can be measured with
      clinical methods or derived from the biometric data of the eye and the measured
      ACD decrease using geometrical optics. For clinical purposes, pseudophakic
      accommodation should be assessed with a variety of different techniques,
      including subjective and objective measurements. The theoretical approach using
      geometrical optics may be an additional indicator for the accommodative response
      in patients with pseudophakic eyes and may allow a subdivision of the measured
      accommodation into true pseudophakic accommodation and pseudoaccommodation.

PMID- 14662593
TI  - Progression of age-related macular degeneration: association with dietary fat,
      transunsaturated fat, nuts, and fish intake.
AB  - BACKGROUND: Individuals with early or intermediate stages of age-related macular
      degeneration (AMD) make up a large, growing segment of the elderly population.
      Evidence is sparse regarding modifiable factors that may decrease the risk of
      progression to the advanced forms of AMD. OBJECTIVE: To advise patients with a
      high risk for advanced forms of AMD about preventive measures through our
      evaluation of the relationship between dietary fat intake and the progression of
      early or intermediate AMD to the advanced stages of the disease associated with
      visual loss. DESIGN: A prospective cohort study with an average follow-up time of
      4.6 years. SETTING: A hospital-based clinical retinal practice specializing in
      macular degeneration. Patients The 261 participants were aged 60 years and older
      and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at
      least 1 eye. Main Outcome Measure Progression to advanced AMD, which was defined
      as having geographic atrophy or neovascular disease. RESULTS: Higher total fat
      intake increased the risk of progression to the advanced forms of AMD, with a
      relative risk (RR) of 2.90 (95% confidence interval, 1.15-7.32) for the highest
      fat-intake quartile relative to the lowest fat-intake quartile, after controlling
      for other factors (P trend =.01). Animal fat intake was associated with a 2-fold
      increased risk of progression (RR, 2.29 for the highest quartile compared with
      the lowest quartile; 95% confidence interval, 0.91-5.72), although the trend for
      increasing risk with higher animal fat intake was not significant (P=.09). Higher
      vegetable fat intake had a stronger relationship with increased risk of AMD
      progression with an RR of 3.82 (95% confidence interval, 1.58-9.28) for the
      highest quartile compared with the lowest quartile (P trend =.003). Saturated,
      monounsaturated, polyunsaturated, and transunsaturated fats increased the
      likelihood of progression (RR, 2.09 and P trend =.08; RR, 2.21 and P trend =.04;
      RR, 2.28 and P trend =.04; RR, 2.39 and P trend =.008, respectively). Higher fish
      intake was associated with a lower risk of AMD progression among subjects with
      lower linoleic acid intake. Processed baked goods, which are higher in some of
      these fats, increased the rate of AMD progression approximately 2-fold, and nuts
      were protective. CONCLUSIONS: Among individuals with the early or intermediate
      stages of AMD, total and specific types of fat intake, as well as some fat
      containing food groups, modified the risk of progression to advanced AMD. Fish
      intake and nuts reduced risk. Since advanced AMD is associated with visual loss
      and reduced quality of life, these preventive measures deserve additional
      research and greater emphasis.

PMID- 14662594
TI  - Rod photoreceptor responses in children with Smith-Lemli-Opitz syndrome.
AB  - OBJECTIVE: To test the hypothesis that the kinetics of activation and
      deactivation of rod phototransduction are altered in children with Smith-Lemli
      Optiz syndrome (SLOS), a common genetic disorder caused by an inborn error in
      cholesterol biosynthesis. METHODS: Thirteen patients with SLOS (median age, 4
      years) were studied by means of scotopic full-field electroretinography. The
      kinetics of activation and deactivation of rod phototransduction were derived
      from the electroretinographic a-wave. Postreceptoral electroretinographic
      components were also evaluated. RESULTS: The kinetics of activation were below
      normal limits in all but 3 of the 13 patients. Rod cell recovery (deactivation)
      in SLOS was slower than normal in all 8 patients in whom it was studied.
      Postreceptoral sensitivity was below normal limits in all but 1 of the 13
      patients. CONCLUSIONS: The kinetics of phototransduction are slow in children
      with SLOS. This is likely a consequence of altered sterol composition in the cell
      membranes of the rod photoreceptors. To our knowledge, this is the first
      demonstration of altered kinetics of a membrane-bound signaling system in SLOS.
      Investigation of other membrane-bound signaling systems may be warranted in the
      quest to understand development and phenotype of individuals with SLOS.

PMID- 14662595
TI  - Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein
      angiographic lesions in galactose-fed dogs.
AB  - OBJECTIVE: To assess the effect of aldose reductase inhibitor (ARI) M79175 (2
      methyl-6-fluoro-spiro-chroman-4-5'-imidazolidine-2',4'-dione) administration and
      galactose withdrawal on the progression of retinal changes using fluorescein
      angiography in galactose-fed dogs. METHODS: Thirty male beagles were randomized
      into 4 groups. Three dogs were fed a normal control diet containing 30%
      nonnutritive fiber for 74 months (control group), 11 dogs a 30% galactose diet
      for 74 months (continuous galactose group), 8 dogs a 30% galactose diet for 36
      months followed by replacement with a normal diet for 36 months (galactose
      withdrawal group), and 8 dogs a 30% galactose diet supplemented with M79175 for
      34 months followed by replacement with a normal diet and removal of M79175
      treatment for 38 months (ARI-treated galactose withdrawal group). Stereoscopic
      color fundus photography and fluorescein angiography, performed at baseline and
      follow-up, were assessed for the clinical development of retinopathy, including
      the first appearance of hyperfluorescence, varying severity of retinal
      nonperfusion, and retinal neovascularization. Histopathologic features were
      examined in selected dogs. RESULTS: All dogs in the 3 groups fed the 30%
      galactose diet developed areas of hyperfluorescence and nonperfusion. Of these
      dogs, only those supplemented with the ARI did not develop areas of nonperfusion
      greater than or equal to half the field and retinal neovascularization.
      Parametric survival analysis showed significant differences (galactose withdrawal
      group vs ARI-treated galactose withdrawal group) in the median times to the
      development of nonperfusion greater than or equal to half the field (P =.003) and
      retinal neovascularization (P =.03). CONCLUSION: Normalization of glycemic
      control with galactose withdrawal and ARI treatment may delay the onset and
      progression of retinal lesions in galactose-fed dogs. Clinical Relevance Perfect
      glycemic control after a period of poor control does not completely prevent the
      progression of retinal lesions. Therapy with ARIs may potentially be important in
      the prevention of retinal lesions associated with diabetic eye disease.

PMID- 14662596
TI  - Hereditary hyperferritinemia-cataract syndrome: prevalence, lens morphology,
      spectrum of mutations, and clinical presentations.
AB  - OBJECTIVES: To provide a comprehensive description of the clinical presentations,
      cataract morphology, and molecular basis of hereditary hyperferritinemia-cataract
      syndrome (HHCS) in 4 Australian pedigrees and to estimate its prevalence.
      METHODS: All known cases of HHCS in southeastern Australia were ascertained.
      Family members provided a medical history and underwent physical examination,
      lens photography, and venipuncture for measurement of serum ferritin levels and
      DNA extraction. Sequence analysis of the iron-responsive element of the ferritin
      light chain on chromosome 19q13.3-qter was performed. RESULTS: We investigated 26
      affected individuals from 5 Australian pedigrees. Two pedigrees with HHCS
      ascertained independently were subsequently found to form 1 large kindred
      carrying the mutation A40G. The minimum estimated prevalence of HHCS is 1/200000.
      One pedigree had the mutation G32C. Among 2 smaller pedigrees studied, one
      carried a novel mutation (C39A), and the other was identified through the 2-year
      old propositus with cataract but no positive family history. The latter case was
      shown to be due to a de novo mutation (G32U). All cataracts were highly
      distinctive in morphology, consisting of slowly progressive flecks, vacuoles, and
      distinctive crystalline deposits scattered predominantly in the lens cortex but
      also in the nucleus. Eight of 18 affected individuals examined have required
      cataract extraction to date. No other identified clinical manifestations of HHCS
      were delineated. CONCLUSIONS: Cataract morphology in HHCS is highly distinctive.
      Longitudinal observation demonstrated slow progression of the cataracts. This
      study highlights that, although HHCS is an autosomal dominant condition, the
      diagnosis should be considered even in sporadic cataract of typical morphology.
      Furthermore, individuals with unexplained hyperferritinemia should be referred
      for ophthalmological assessment, as the cataract may be asymptomatic but lead to
      a correct diagnosis of HHCS. Clinical Relevance Progressive cataracts of highly
      distinctive morphology are an important feature of HHCS. Evaluation for this type
      of cataract may be of diagnostic value in patients with unexplained
      hyperferritinemia. Hereditary hyperferritinemia-cataract syndrome can be a cause
      of cataracts in pediatric patients even in the absence of any positive family
      history.

PMID- 14662597
TI  - Prospective study of cigarette smoking and the risk of primary open-angle
      glaucoma.
AB  - OBJECTIVE: To examine the association between cigarette smoking and incident
      primary open-angle glaucoma (POAG). METHODS: Female nurses and male health
      professionals were prospectively followed up from 1980 and 1986, respectively, to
      1996. Participants were at least 40 years old, were free of diagnosed glaucoma at
      baseline, and reported being examined by an ophthalmologist or optometrist during
      follow-up. Smoking history and other POAG risk factors were updated with biennial
      questionnaires. A total of 450 incident cases of POAG were identified. Both
      cohort-specific proportional hazards analyses and analyses pooled across cohorts
      were conducted. RESULTS: After controlling for potential risk factors of POAG,
      including age, hypertension, and African American heritage, neither current
      smokers (relative risk, 0.85; 95% confidence interval, 0.62-1.18) nor past
      smokers (relative risk, 0.91; 95% confidence interval, 0.63-1.32) were at greater
      risk for POAG than those who had never smoked. Heavier smoking did not increase
      the risk of POAG. A modest inverse association was observed with pack-years of
      smoking: those with 30 or more pack-years had a 22% reduced risk of POAG
      (relative risk, 0.78; 95% confidence interval, 0.55-1.11; P for linear trend,.06)
      than those who had never smoked. CONCLUSION: Cigarette smoking is not an
      important risk factor for POAG.

PMID- 14662599
TI  - Interpolated conjunctival pedicle flaps for the treatment of exposed glaucoma
      drainage devices.
AB  - OBJECTIVE: To describe an alternative method to repair exposed glaucoma drainage
      devices (GDDs) when conventional attempts have failed. METHODS: Four eyes, from 3
      patients, with severe ocular surface disease were included in the study. All eyes
      had previously received a Baerveldt GDD for uncontrollable intraocular pressure
      and postoperatively had exposed GDDs. The conjunctival defects were unrepairable
      with a scleral patch or pericardium, conjunctival advancement, or a conjunctival
      patch graft. Two eyes had chemical burns, one eye had extensive scarring from
      multiple surgical procedures, and one patient had rheumatoid arthritis. Each
      patient provided informed consent, and was given the option of removing the GDD
      and undergoing diode cyclophotocoagulation or attempting to save the GDD by a
      conjunctival pedicle flap. An interpolated conjunctival pedicle flap was taken
      from the cul-de-sac (fornix). The conjunctiva and Tenon capsule were incised
      radially to the tube, rotated from the fornix at a 90 degrees angle, and sutured
      to the remaining healthy conjunctiva to cover the exposed tube. RESULTS:
      Postoperatively, all eyes had vascularized flaps that showed viable tissue. All
      eyes retained the GDDs, and the intraocular pressure has been under control
      during follow-up (7, 13, 25, and 27 months). CONCLUSION: Interpolated
      conjunctival pedicle flaps seem to be a viable alternative to repairing exposed
      GDDs when other methods are impractical or impossible.

PMID- 14662598
TI  - Preliminary results of treatment of eyes with high-risk prethreshold retinopathy
      of prematurity in the early treatment for retinopathy of prematurity randomized
      trial.

PMID- 14662600
TI  - Benign fibrous histiocytoma of the corneoscleral limbus: unique clinicopathologic
      features.

PMID- 14662601
TI  - Conjunctival melanoma with a positive sentinel lymph node.

PMID- 14662602
TI  - Metastasis of acinic cell carcinoma of the parotid gland to the contralateral
      orbit.

PMID- 14662603
TI  - Retinal astrocytic hamartomas: unexpected findings in a giant panda.

PMID- 14662604
TI  - Adverse ocular effects from over-the-counter lice shampoo.

PMID- 14662605
TI  - Intraocular melanocytoma in association with bone formation.

PMID- 14662606
TI  - Atypical manifestation of multiple evanescent white dot syndrome with large
      peripapillary lesion.

PMID- 14662607
TI  - Bilateral congenital trigemino-abducens synkinesis.

PMID- 14662608
TI  - An unusual case of solar retinopathy.

PMID- 14662609
TI  - Treatment of macrostriae and epithelial ingrowth following laser in situ
      keratomileusis with interrupted sutures.

PMID- 14662610
TI  - One hundred transient monocular central retinal artery occlusions secondary to
      giant cell arteritis.

PMID- 14662611
TI  - Balloon catheter reuse in children with bilateral nasolacrimal duct obstruction.

PMID- 14662613
TI  - Random measurement error in assessing compensatory ocular countertorsion.

PMID- 14662615
TI  - Compensatory ocular torsion.

PMID- 14662616
TI  - Frontal air bags and eye injury patterns in automobile crashes.

PMID- 14662619
TI  - Economy class syndrome: too much flying or too much sitting?

PMID- 14662620
TI  - Overcome clinical inertia to control systolic blood pressure.

PMID- 14662621
TI  - What do good doctors try to do?

PMID- 14662622
TI  - Do-not-resuscitate orders and medical futility.
AB  - This report addresses the difficult situation in which a patient or surrogate
      decision maker wishes cardiopulmonary resuscitation to be attempted even though
      the physician believes that resuscitation efforts would be futile. It also
      reviews current controversies surrounding the subject of do-not-resuscitate (DNR)
      orders and medical futility, discusses the complex medical, legal, and ethical
      considerations involved, and then offers recommendations as a guide to clinicians
      and ethics committees in resolving these difficult issues. Conflicts over DNR
      orders and medical futility should not be resolved through a policy that attempts
      to define futility in the abstract, but rather through a predefined and fair
      process that addresses specific cases and includes multiple safeguards. As it
      examines these issues, the report focuses on the Veterans Health Administration
      (VHA). Current national VHA policy constrains physicians from entering a DNR
      order over the objection of a patient or surrogate even if the physician believes
      cardiopulmonary resuscitation to be futile. The VHA National Ethics Committee
      recommends that VHA policy be changed to reflect the opinions expressed in this
      report. The National Ethics Committee, which is composed of VHA clinicians and
      leaders, as well as veterans advocates, creates reports that analyze ethical
      issues affecting the health and care of veterans treated in the VHA, the largest
      integrated health care system in the United States. This report does not change
      or modify VHA policy.

PMID- 14662623
TI  - Role of the natriuretic peptide system in cardiorenal protection.
AB  - Significant progress has been made in the understanding of the neurohormonal
      factors that contribute to the progression of chronic renal and cardiac failure
      and the development of target-organ damage in patients with hypertension and
      diabetes. We herein review some of these advances, including a new therapeutic
      strategy for potentially enhancing cardiorenal protection in patients with these
      disorders.

PMID- 14662624
TI  - Hypertension control: how well are we doing?
AB  - BACKGROUND: We compared blood pressure (BP) control in a recent cohort of
      hypertensive military veterans with BP control in a previous cohort and examined
      whether hypertension treatment practices, as defined by the frequency of
      antihypertensive medication dosage increases, have changed over time. METHODS: We
      abstracted 1999 outpatient chart data including visit type, BP measurements,
      comorbidities, and medication use for 981 randomly selected hypertensive
      veterans. We examined overall BP control and control in subgroups with diabetes
      mellitus and renal disease, and compared results with those of a sample of 800
      veterans studied from 1990 to 1995. We also compared the frequency of
      antihypertensive medication dosage increases in the 2 samples. RESULTS: Mean BPs
      were significantly lower in 1999. The mean systolic drop was 3.1 mm Hg and
      reached 13.7 mm Hg for the subgroups with diabetes and renal disease. Even larger
      decreases were seen in mean diastolic BPs. In 1999, 57% of patients had BP
      measurements of 140/90 mm Hg or higher, vs 69% of patients in the 1990-1995 study
      (P<.001). In 1999, the BP control of patients with diabetes was similar to that
      of patients without diabetes, as 60% of the former had BP measurements of 140/90
      mm Hg or higher. Patients with renal disease had better control than those
      without, however, as only 43% had BP measurements of 140/90 mm Hg or higher. When
      comparing samples, patients with diabetes, renal disease, or both had better BP
      control in 1999 than their counterparts in the 1990-1995 study (P<.003 in all
      cases). In 1999, more medical visits were associated with medication dosage
      increases than in the 1990-1995 study. CONCLUSIONS: Although overall BP control
      has improved, BP measurements still exceeded recommended levels in most patients.
      For patients with diabetes and renal disease BP was much better controlled in the
      more recent sample. However, BP control of patients with diabetes was similar to
      that of patients without diabetes, and not in agreement with the guideline
      recommended tighter control. Thus, room for improvement remains, especially in
      this subgroup.

PMID- 14662625
TI  - Updating the Beers criteria for potentially inappropriate medication use in older
      adults: results of a US consensus panel of experts.
AB  - BACKGROUND: Medication toxic effects and drug-related problems can have profound
      medical and safety consequences for older adults and economically affect the
      health care system. The purpose of this initiative was to revise and update the
      Beers criteria for potentially inappropriate medication use in adults 65 years
      and older in the United States. METHODS: This study used a modified Delphi
      method, a set of procedures and methods for formulating a group judgment for a
      subject matter in which precise information is lacking. The criteria reviewed
      covered 2 types of statements: (1) medications or medication classes that should
      generally be avoided in persons 65 years or older because they are either
      ineffective or they pose unnecessarily high risk for older persons and a safer
      alternative is available and (2) medications that should not be used in older
      persons known to have specific medical conditions. RESULTS: This study identified
      48 individual medications or classes of medications to avoid in older adults and
      their potential concerns and 20 diseases/conditions and medications to be avoided
      in older adults with these conditions. Of these potentially inappropriate drugs,
      66 were considered by the panel to have adverse outcomes of high severity.
      CONCLUSIONS: This study is an important update of previously established criteria
      that have been widely used and cited. The application of the Beers criteria and
      other tools for identifying potentially inappropriate medication use will
      continue to enable providers to plan interventions for decreasing both drug
      related costs and overall costs and thus minimize drug-related problems.

PMID- 14662626
TI  - Extent of cardiovascular risk reduction associated with treatment of isolated
      systolic hypertension.
AB  - BACKGROUND: The Systolic Hypertension in the Elderly Program (SHEP) demonstrated
      the benefit of treating isolated systolic hypertension (ISH) in older adults.
      However, nearly 20% of older adults remain at high risk of heart disease and
      stroke from untreated ISH. METHODS: For the Pittsburgh SHEP cohort, 11- to 14
      year death or cardiovascular event rates were compared for active (n = 135) and
      placebo (n = 133) arms plus normotensive controls (n = 187). Carotid ultrasound
      and ankle blood pressures were used to identify subclinical atherosclerosis at
      baseline. RESULTS: Fourteen-year Kaplan-Meier event rate estimates were 58% vs
      79% for the active vs placebo groups (P =.001). Eleven-year event rates for the
      control, active, and placebo groups were 35%, 47%, and 65%, respectively.
      Compared with controls, the relative risk of an event was 1.6 (95% confidence
      interval, 1.1-2.4) for the active treatment group and 3.0 (95% confidence
      interval, 2.1-4.4) for the placebo group. Baseline history of cardiovascular
      disease was present in 19% of SHEP participants vs 15% of controls (P =.32), and
      subclinical disease (carotid stenosis or low ankle blood pressure) was detected
      in 33% of SHEP participants vs 10% of controls (P<.001). Among those with no
      clinical or subclinical disease at baseline, the ISH group assigned to active
      treatment had 10-year event rates similar to those of the control group (29% vs
      27%), whereas the placebo rates were much higher (69%). CONCLUSIONS: Treatment of
      ISH in older adults results in reduced event rates in 14 years. Treatment before
      advanced atherosclerosis develops will likely produce the best long-term outcome.

PMID- 14662627
TI  - Leaving the practice: effects of primary care physician departure on patient
      care.
AB  - BACKGROUND: Recent changes in the organization of health care services, coupled
      with rising rates of primary care physician (PCP) turnover, pose threats to the
      maintenance of a continuous patient-physician relationship. Little is known,
      however, about how PCP departure may affect patients' quality of health care.
      METHODS: Participants were adult patients whose PCPs left a large, multispecialty
      group practice from July 1, 1994, to June 30, 1996 (n = 3931), and adult patients
      of a set of matched PCPs who remained in the practice at least 2 years beyond the
      index PCPs departure dates (n = 8009). We compared the following measures of
      quality of care: adherence to recommended screening guidelines, adequacy of blood
      pressure and glycemic control in patients with hypertension and/or diabetes
      mellitus, and use of urgent care and emergency department services. RESULTS:
      Among the women who received a mammogram in the 2-year baseline period, a higher
      proportion of those whose PCP departed did not continue to receive mammograms,
      although the difference did not reach statistical significance (8.4% vs 5.1%; P
      =.08). For patients who had screening Papanicolaou smears or fecal occult blood
      testing during the baseline period, there was no significant difference between
      study and control groups in the likelihood that patients discontinued screening
      during the follow-up period (10.9% vs 10.7%; P =.93 and 28.8% vs 25.3%; P =.93,
      respectively). Similarly, diabetic patients of departed PCPs did not have higher
      risk of worsening glycemic control (31.7% vs 28.9%; P =.46); and hypertensive
      patients of departed PCPs actually had lower risks of worsening blood pressure
      control (16.5% vs 22.5%; P =.02). There was no difference in use of urgent care
      or emergency department services between patient groups. CONCLUSIONS: In this
      multispecialty group practice, patients of departed PCPs experienced little or no
      decrease in quality of care measures for routine screening, management of chronic
      disease, and use of urgent care and emergency department services.

PMID- 14662628
TI  - Limb fractures in elderly men as indicators of subsequent fracture risk.
AB  - BACKGROUND: Whether limb fracture in elderly men predicts future fracture is
      unknown. METHODS: Electronic health records were examined to determine fracture
      incidence among men 60 years or older who were members of a large health
      maintenance organization, experienced no fracture in the past 2 years, and
      experienced an ankle, hip, humerus, or wrist fracture between July 1, 1997, and
      August 31, 2001. Proportional hazards models were used to compare risk of new
      fracture (ankle, hip, humerus, or wrist) between groups. Recurrent fractures of
      the same type were excluded from analysis. RESULTS: During the follow-up period
      (mean duration, 2.4 years), 0.5% of the control subjects without fractures
      experienced a subsequent ankle fracture; 0.6%, a hip fracture; 0.2%, a humerus
      fracture; and 0.4%, a wrist fracture. A limb fracture was about 4 times more
      likely to occur in persons who experienced a previous humerus fracture (relative
      risk, 3.9; 95% confidence interval, 2.5-6.0), about 3 times more likely to occur
      in persons who experienced a previous hip fracture (relative risk, 2.8; 95%
      confidence interval, 1.7-4.5), and about 2 times more likely to occur in persons
      who experienced a previous wrist fracture (relative risk, 2.2; 95% confidence
      interval, 1.4-3.5) than in controls. In contrast, persons who experienced a
      previous ankle fracture had no greater risk of subsequent fracture than
      nonfracture controls (relative risk, 1.0; 95% confidence interval, 0.5-1.9).
      CONCLUSIONS: Among men 60 years or older, a recent hip, humerus, or wrist
      fracture is a statistically and clinically significant predictor of future limb
      fracture risk. An increased risk of future fracture is greatest after a humerus
      fracture and is lowest after a wrist fracture; however, among elderly men, a
      previous ankle fracture is not an indicator of future fracture risk.

PMID- 14662629
TI  - Primary care physician preferences regarding spiritual behavior in medical
      practice.
AB  - BACKGROUND: Knowledge of physician attitudes and preferences regarding religion
      and spirituality in the medical encounter is limited by the nonspecific questions
      asked in previous studies and by the omission of specialties other than family
      practice. This study was designed to determine the willingness of internists and
      family physicians to be involved with varying degrees of spiritual behaviors in
      varied clinical settings. METHODS: The study was a multicenter, cross-sectional,
      nonrandomized design recruiting physicians from 6 teaching hospitals with sites
      in North Carolina, Vermont, and Florida. A self-administered survey was used to
      explore physicians' willingness to address religion and spirituality in the
      medical encounter. Data were gathered on the physicians' religiosity and
      spirituality and sociodemographic characteristics. RESULTS: Four hundred seventy
      six physicians responded, for a response rate of 62.0%. While 84.5% of physicians
      thought they should be aware of patients' spirituality, most would not ask about
      spiritual issues unless a patient were dying. Fewer than one third of physicians
      would pray with patients even if they were dying. This number increased to 77.1%
      if a patient requested physician prayer. Family practitioners were more likely to
      take a spiritual history than general internists. CONCLUSIONS: Most primary care
      physicians surveyed would not initiate any involvement with patients'
      spirituality in the medical encounter except for the clinical setting of dying.
      If a patient requests involvement, however, most physicians express a willingness
      to comply, even if the request involves prayer.

PMID- 14662630
TI  - Venous thrombosis after long-haul flights.
AB  - BACKGROUND: The risk for venous thromboembolism after long-haul flights
      represents a controversial issue. The aim of our study was to assess the
      incidence of venous thrombosis associated with long-haul flights in a
      prospective, controlled cohort study. METHODS: We included 964 passengers
      returning from long-haul flights (flight duration, > or =8 hours) and 1213
      nontraveling control subjects. We excluded participants who were being treated
      with anticoagulant drugs or who used compression stockings. Main outcome measures
      were the incidence of ultrasonographically diagnosed thrombosis in the calf
      muscle and deep veins, symptomatic pulmonary embolism, and death. RESULTS: We
      diagnosed venous thrombotic events in 27 passengers (2.8%) and 12 controls (1.0%)
      (risk ratio [RR], 2.83; 95% confidence interval [CI], 1.46-5.49). Of these, 20
      passengers (2.1%) and 10 controls (0.8%) presented with isolated calf muscle
      venous thrombosis (RR, 2.52; 95% CI, 1.20-5.26), whereas 7 passengers (0.7%) and
      2 controls (0.2%) presented with deep venous thrombosis (RR, 4.40; 95% CI, 1.04
      18.62). Symptomatic pulmonary embolism was diagnosed in 1 passenger with deep
      venous thrombosis (P =.44). All of these individuals had normal findings at
      baseline ultrasonography. Passengers with isolated calf muscle venous thrombosis
      or deep venous thrombosis had at least 1 risk factor for venous thrombosis (>45
      years of age or elevated body mass index in 21 of 27 passengers). The follow-up
      after 4 weeks revealed no further venous thromboembolic event. CONCLUSIONS: Long
      haul flights of 8 hours and longer double the risk for isolated calf muscle
      venous thrombosis. This translates into an increased risk for deep venous
      thrombosis as well. In our study, flight-associated thrombosis occurred
      exclusively in passengers with well-established risk factors for venous
      thrombosis.

PMID- 14662631
TI  - Incidence of air travel-related pulmonary embolism at the Madrid-Barajas airport.
AB  - BACKGROUND: Prolonged air travel and the associated immobilization are risk
      factors for venous thromboembolism. The occurrence of pulmonary thromboembolism
      (PTE) under these circumstances is referred to as economy class syndrome. We
      assessed the incidence of symptomatic PTE in passengers on long-haul flights
      arriving at Madrid-Barajas Airport, Madrid, Spain, and the association with the
      number of flight hours. METHODS: We retrospectively reviewed cases of PTE among
      international travelers arriving at Madrid-Barajas Airport between January 1995
      and December 2000. Patients presenting with symptoms of deep venous thrombosis
      but without symptoms of PTE were excluded. Pulmonary thromboembolism was
      identified using an algorithm of diagnostic tests. The incidence of PTE and the
      association with flight duration was assessed. RESULTS: The average number of
      passengers per year who arrived at the airport on flights originating abroad in
      the period analyzed was 6 839 222. Sixteen cases of PTE were detected over the 6
      year period. All patients with travel-associated PTE had flight durations of
      greater than 6 hours. The overall incidence of PTE was 0.39 per 1 million
      passengers (95% confidence interval [CI], 0.20-0.58). On flights that lasted
      between 6 and 8 hours, the incidence was 0.25 per 1 million passengers (95% CI, 0
      0.75), while on flights longer than 8 hours, the incidence was 1.65 per 1 million
      passengers (95% CI, 0.81-2.49) (P<.001). CONCLUSIONS: Air travel is a risk factor
      for PTE, and the incidence of PTE increases with the duration of the air travel.
      However, the low incidence of PTE among long-distance passengers, similar to that
      observed in other international airports, does not justify social alarm.

PMID- 14662632
TI  - Risk of venous thromboembolism after air travel: interaction with thrombophilia
      and oral contraceptives.
AB  - BACKGROUND: Conflicting data are available on air travel as a risk factor for
      venous thromboembolism. To our knowledge, there are no studies investigating
      whether individuals with thrombophilia and those taking oral contraceptives are
      more likely to develop venous thromboembolism during flights than those without
      these risk factors. PARTICIPANTS AND METHODS: The study sample consisted of 210
      patients with venous thromboembolism and 210 healthy controls. DNA analysis for
      mutations in factor V and prothrombin genes and plasma measurements of
      antithrombin, protein C, protein S, total homocysteine levels, and
      antiphsopholipid antibodies were performed. RESULTS: In the month preceding
      thrombosis for patients, or the visit for controls, air travel was reported by 31
      patients (15%) and 16 controls (8%), with an oddsratio of 2.1 (95% confidence
      interval, 1.1-4.0). Thrombophilia was present in 102 patients (49%) and 26
      controls (12%), and oral contraceptives were used by 48 patients and 19 controls
      (61% and 27% of those of reproductive age, respectively). After stratification
      for the presence of air travel and thrombophilia, the odds ratio for thrombosis
      in individuals with both risk factors was 16.1 (95% confidence interval, 3.6
      70.9). Stratification for the presence of air travel and oral contraceptive use
      gave an odds ratio of 13.9 (95% confidence interval, 1.7-117.5) in women with
      both risk factors. CONCLUSIONS: Air travel is a mild risk factor for venous
      thromboembolism, doubling the risk of the disease. When thrombophilia or oral
      contraceptive use is present, the risk increases to 16-fold and 14-fold,
      respectively, indicating a multiplicative interaction.

PMID- 14662634
TI  - Relative risk of physicians and nurses to transmit pathogens in a medical
      intensive care unit.

PMID- 14662633
TI  - Coaching patients On Achieving Cardiovascular Health (COACH): a multicenter
      randomized trial in patients with coronary heart disease.
AB  - BACKGROUND: Disease management programs in which drugs are prescribed by
      dietitians or nurses have been shown to improve the coronary risk factor profile
      in patients with coronary heart disease. However, those disease management
      programs in which drugs are not prescribed by allied health professionals have
      not improved coronary risk factor status. The objective of the Coaching patients
      On Achieving Cardiovascular Health (COACH) study was to determine whether
      dietitians or nurses who did not prescribe medications could coach patients with
      coronary heart disease to work with their physicians to achieve the target levels
      for their total cholesterol (TC) and other risk factors. METHODS: Multicenter
      randomized controlled trial in which 792 patients from 6 university teaching
      hospitals underwent a stratified randomization by cardiac diagnosis within each
      hospital: 398 were assigned to usual care plus The COACH Program and 394 to usual
      care alone. Patients in The COACH Program group received regular personal
      coaching via telephone and mailings to achieve the target levels for their
      particular coronary risk factors. There was one coach per hospital. The primary
      outcome was the change in TC (DeltaTC) from baseline (in hospital) to 6 months
      after randomization. Secondary outcomes included measurement of a wide range of
      physical, nutritional, and psychological factors. The analysis was performed by
      intention to treat. RESULTS: The COACH Program achieved a significantly greater
      DeltaTC than usual care alone: the mean DeltaTC was 21 mg/dL (0.54 mmol/L) (95%
      confidence interval [CI], 16-25 mg/dL [0.42-0.65 mmol/L]) in The COACH Program vs
      7 mg/dL (0.18 mmol/L) (95% CI, 3-11 mg/dL [0.07-0.29 mmol/L]) in the usual care
      group (P<.0001). Thus, the reduction in TC from baseline to 6 months after
      randomization was 14 mg/dL (0.36 mmol/L) (95% CI, 8-20 mg/dL [0.20-0.52 mmol/L])
      greater in The COACH Program group than in the usual care group. Coaching
      produced substantial improvements in most of the other coronary risk factors and
      in patient quality of life. CONCLUSIONS: Coaching, delivered as The COACH
      Program, is a highly effective strategy in reducing TC and many other coronary
      risk factors in patients with coronary heart disease. Coaching has potential
      effectiveness in the whole area of chronic disease management.

PMID- 14662635
TI  - The metabolic syndrome: all criteria are equal, but some criteria are more equal
      than others.

PMID- 14662636
TI  - Anticoagulation of pregnant women with mechanical heart valves using low
      molecular-weight heparin.

PMID- 14662637
TI  - Fondaparinux and prolonged thromboprophylaxis after hip fracture surgery.

PMID- 14662638
TI  - Is angiotensin receptor blockade antithrombotic?

PMID- 14662639
TI  - Vascular protection of ACE inhibitors.

PMID- 14662640
TI  - Role of the renin-angiotensin system in the pathogenesis of vascular disease.

PMID- 14662641
TI  - Recurrent thromboembolism after treatment with vitamin K antagonists.

PMID- 14662642
TI  - Transmission patterns and risk factors of HCV infection.

PMID- 14662643
TI  - Clinical relevance of bleeding index.

PMID- 14662644
TI  - Cost-effective, risk-free, evidence-based medicine.

PMID- 14662645
TI  - Fractures, osteoporosis, and the endocrinologist.

PMID- 14662648
TI  - Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion
      through activation of Akt-GSK signaling.
AB  - Adrenomedullin (AM) is a potent vasoactive peptide and plays an important role in
      cardiovascular function. In this study, we delivered the AM gene locally into the
      heart, using a catheter-based technique to investigate the signaling mechanism
      mediated by AM in protection against cardiomyocyte apoptosis induced by acute
      ischemia/reperfusion. After adenovirus-mediated gene delivery, highly efficient
      and specific expression of luciferase, green fluorescent protein, or recombinant
      human AM was identified in the left ventricle. Delivery of the AM gene 5 days
      before ischemia/reperfusion attenuated myocardial apoptosis identified by in situ
      dUTP nick-end labeling and DNA laddering, and the effect was blocked by the AM
      antagonist human calcitonin gene-related peptide (CGRP 8 to 37). AM gene transfer
      increased phosphorylation of Akt and glycogen synthase kinase (GSK-3beta) but
      reduced GSK-3beta and caspase-3 activities in the heart. The effects of AM on GSK
      3beta and caspase-3 activities were blocked by CGRP (8-37) and by adenovirus
      containing dominant-negative Akt (DN-Akt). Furthermore, in cultured
      cardiomyocytes, AM also attenuated apoptosis induced by hypoxia/reoxygenation,
      which was accompanied by increased phospho-GSK-3beta but reduced GSK-3 and
      caspase-3 activities. GSK-3 and caspase-3 activities were both blocked by Ad.DN
      Akt and lithium, whereas only caspase-3 was inhibited by its inhibitor Z-VAD. The
      effects of AM on anti-apoptosis and promoting cell viability were blocked by DN
      Akt but not by constitutively active Akt, lithium, or Z-VAD. These results
      indicate that AM protects against cardiomyocyte apoptosis induced by
      ischemia/reperfusion injury through the Akt-GSK-caspase signaling pathway.

PMID- 14662649
TI  - High blood pressure in acute stroke and subsequent outcome: a systematic review.
AB  - High blood pressure (BP) is common in acute stroke and might be associated with a
      poor outcome, although observational studies have given varying results. In a
      systematic review, articles were sought that reported both admission BP and
      outcome (death, death or dependency, death or deterioration, stroke recurrence,
      and hematoma expansion) in acute stroke. Data were analyzed by the Cochrane
      Review Manager software and are given as odds ratios (ORs) or weighted mean
      differences (WMDs) with 95% confidence intervals (CIs). Altogether, 32 studies
      were identified involving 10 892 patients. When all data were included, death was
      significantly associated with an elevated mean arterial BP ([MABP] OR, 1.61; 95%
      CI, 1.12 to 2.31) and a high diastolic BP ([DBP] OR, 1.71; 95% CI, 1.33 to 2.48).
      Combined death or dependency was associated with high systolic BP ([SBP] OR,
      2.69; 95% CI, 1.13 to 6.40) and DBP (OR, 4.68; 95% CI, 1.87 to 11.70) in primary
      intracerebral hemorrhage (PICH). Similarly, high SBP (+11.73 mm Hg; 95% CI, 1.30
      to 22.16), MABP (+9.00 mm Hg; 95% CI, 0.92 to 17.08), and DBP (+6.00 mm Hg; 95%
      CI, 0.19 to 11.81) were associated with death or dependency in ischemic stroke.
      Combined death or deterioration was associated with a high SBP (OR, 5.57; 95% CI,
      1.42 to 21.86) in patients with PICH. In summary, high BP in acute ischemic
      stroke or PICH is associated with subsequent death, death or dependency, and
      death or deterioration. Moderate lowering of BP might improve outcome. Acute BP
      lowering needs to be tested in 1 or more large, randomized trials.

PMID- 14662650
TI  - Cardiovascular and renal phenotype in mice with one or two renin genes.
AB  - We compared the phenotype of two common mouse models, C-57BL/6J (C57), which
      carries only the Ren-1c gene, and 129/SvJ (Sv-129), with both Ren 1d and Ren-2.
      We hypothesized two renin gene Sv-129 would have increased blood pressure and the
      renin-angiotensin system would be more influential in regulating renal function
      compared with one renin gene mice. Sv-129 consistently had higher blood pressure
      than C-57, whether conscious (128 versus 108 mm Hg, P<0.001) or anesthetized (102
      versus 88 mm Hg, P<0.001). Plasma renin concentration in both conscious and
      anesthetized C-57 mice was 3- to 4-fold higher than in Sv-129 (P<0.05), whereas
      renal cortical renin content was 2.5-fold higher (P<0.005). Renal blood flow and
      renal vascular resistance were the same in C-57 and Sv-129. Exogenous
      angiotensinogen produced identical pressor and renal vasoconstrictor responses in
      both strains. Blocking AT1 receptors with losartan reduced blood pressure by 19
      mm Hg in both strains. Nitric oxide synthase inhibition by l-NAME increased blood
      pressure by 29 mm Hg in C-57 and 35 mm Hg in Sv-129 mice, but the decrease in
      renal blood flow was 30% less in C-57 (P<0.025). We conclude that Sv-129 mice
      with two renin genes have higher blood pressure but lower plasma and renal renin
      than C-57 mice with one renin gene. Renin substrate may limit angiotensin II
      production in the mouse. In Sv-129, the influence of nitric oxide on renal but
      not systemic resistance may be exaggerated. Renin from Ren-2 may act
      independently of normal renin control mechanisms.

PMID- 14662651
TI  - 2-hydroxyoleic acid: a new hypotensive molecule.
AB  - Recent studies have shown that diets rich in monounsaturated fatty acids (MUFAs)
      from olive oil, a natural source of oleic acid, have beneficial effects on blood
      pressure (BP) in hypertensive patients. With this in mind, we investigated
      whether a synthetic derivative of the MUFA oleic acid, 2-hydroxyoleic acid (2
      OHOA), was capable of regulating the BP of Sprague-Dawley rats. Intraperitoneal
      and oral administration of 2-OHOA to rats induced significant and sustained
      decreases in BP in a time-dependent manner. Without affecting heart rate,
      treatments for 7 days provoked reductions in systolic BP of 20 to 26 mm Hg. At
      the molecular level, the density of Galpha(s), but not Galpha(i2) or Galpha(o),
      increased in membranes from the hearts and aortas of 2-OHOA-treated rats, whereas
      in heart membranes, the density of Galpha(q)/11 and protein kinase Calpha
      proteins was also augmented. These molecular alterations were reflected in the
      increase in cAMP levels after Galpha(s) protein and beta-adrenergic receptor
      stimulation. On the contrary, inhibitory hormones reduced adenylyl cyclase
      activity to the same extent in 2-OHOA-treated rats as in vehicle-treated ones.
      Our results indicate that cardiovascular tissues from 2-OHOA-treated rats
      exhibited increased cAMP production in response to Galpha(s) activation, which
      might be attributed to enhanced expression of Galpha(s) proteins. As a result of
      this change, a significant reduction in systolic BP was observed. Therefore, BP
      can be lowered by administration of 2-OHOA, which might represent the first
      member of a new family of antihypertensive drugs.

PMID- 14662652
TI  - Attenuation of lysophosphatidylcholine-induced suppression of ANP release from
      hypertrophied atria.
AB  - Lysophosphatidylcholine (LPC) is an endogenous phospholipid released from the
      cell membrane during ischemia, and it has potent cardiac effects, including
      inhibition of atrial natriuretic peptide (ANP) release. The aim of this study was
      to investigate the effects of LPC on hemodynamics and ANP release in
      hypertrophied atria and to define its mechanism. Isolated, perfused, beating,
      hypertrophied atria from monocrotaline-treated rats were used. LPC (30
      micromol/L), a mixture of stearoyl-LPC, palmitoyl-LPC, and oleoyl-LPC, caused
      suppression of ANP release, which was markedly attenuated in hypertrophied atria
      compared with nonhypertrophied atria. Suppression of ANP release by stearoyl-LPC,
      palmitoyl-LPC, or oleoyl-LPC was also attenuated in hypertrophied atria. The
      potency appeared to be dependent on the species of fatty acid residue of LPC.
      Changes in ANP release by LPC, palmitoyl-LPC, and oleoyl-LPC were positively
      correlated with the degree of cardiac hypertrophy, but that by stearoyl-LPC was
      not. Changes in ANP release by LPC also were negatively correlated with changes
      in pulse pressure. Stearoyl-LPC caused an increase in intracellular Ca2+ in
      single, atrial myocytes in a concentration-dependent manner, which was markedly
      attenuated in hypertrophied atrial myocytes. These results suggest that
      attenuation of LPC-induced suppression of ANP release from hypertrophied atria
      might partly be related to changes in pulse pressure in terms of cardiac
      hypertrophy and/or disturbance of intracellular Ca2+ regulation.

PMID- 14662653
TI  - Expression and molecular characterization of alternative transcripts of the
      ARHGEF5/TIM oncogene specific for human breast cancer.
AB  - The ARHGEF5/TIM oncogene belongs to the Dbl family of guanine nucleotide exchange
      factors (GEFs) for Rho GTPases. It is well established that Rho-GEFs play an
      important role in tumorigenesis and metastasis through the activation of their
      substrates, the Rho GTPases. Little is known about ARHGEF5/TIM oncogene
      expression and cellular functions. Because of its localization close to the
      common fragile site FRA7I, which has been shown to be responsible for an inverted
      duplication of the 7q34-q35 region in breast carcinoma cells, we examined the
      expression of the ARHGEF5/TIM oncogene in normal and tumoral breast tissue. We
      report here the identification of five novel ARHGEF5/TIM alternative transcripts
      specifically expressed in breast tumors. These variant transcripts were
      characterized by the absence of one or several exons, all coding for the
      catalytic Dbl-homology domain and generating modified or truncated predicted
      variant proteins. The variant transcripts were predominantly expressed in breast
      carcinoma cell lines and in the most aggressive primary breast carcinomas,
      suggesting they may play a role in breast tumor progression. Moreover, we
      demonstrate that the expression of recombinant ARHGEF5/TIM protein in transfected
      COS-7 and NIH-3T3 cells generated a loss of actin stress fibers and the formation
      of membrane ruffles and filopodia. This pattern suggests that ARHGEF5/TIM
      activates Rac1, Cdc42 or RhoG rather than RhoA, as previously demonstrated in in
      vitro guanine nucleotide exchange assays. We anticipate that the activation of
      the ARHGEF5/TIM oncogene, possibly by the variant isoforms detected here, may
      play an important role in proliferative breast disease.

PMID- 14662654
TI  - Mutations in the human RAX homeobox gene in a patient with anophthalmia and
      sclerocornea.
AB  - Anophthalmia and microphthalmia are among the most common ocular birth defects
      and a significant cause of congenital blindness. The etiology of anophthalmia and
      microphthalmia is diverse, with multiple genetic mutations associated with each
      of these conditions, along with potential environmental causes. Based on findings
      that mutations in the Rx/Rax homeobox genes in mice and fish lead to defects in
      retinal development and result in animal models of anophthalmia, we screened 75
      individuals with anophthalmia and/or microphthalmia for mutations in the human
      RAX gene. We identified a single proband from this population who is a compound
      heterozygote for mutations in the RAX gene. This individual carries a truncated
      allele (Q147X) and a missense mutation (R192Q), both within the DNA-binding
      homeodomain of the RAX protein, and we have characterized the biochemical
      properties of these mutations in vitro. Parents and grandparents of the proband
      were found to be carriers without visible ocular defects, consistent with an
      autosomal recessive inheritance pattern. This is the first report of genetic
      mutations in the human RAX gene.

PMID- 14662655
TI  - Two essential splice lariat branchpoint sequences in one intron in a xeroderma
      pigmentosum DNA repair gene: mutations result in reduced XPC mRNA levels that
      correlate with cancer risk.
AB  - The lariat branch point sequence (BPS) is crucial for splicing of human nuclear
      pre-mRNA yet BPS mutations have infrequently been reported to cause human
      disease. Using an inverse RT-PCR technique we mapped two BPS to the adenosine
      residues at positions -4 and -24 in intron 3 of the human XPC DNA repair gene. We
      identified homozygous mutations in each of these BPS in two newly diagnosed
      Turkish families with the autosomal recessive disorder xeroderma pigmentosum
      (XP). Cells from two severely affected children in family A harbor a homozygous
      point mutation in XPC intron 3 (-9 T to A), located within the downstream BPS.
      Using a real-time quantitative reverse transcriptase-polymerase chain reaction
      (QRT-PCR) assay, these cells expressed no detectable (<0.1%) normal XPC message.
      Instead they expressed an XPC mRNA isoform with deletion of exon 4 that has no
      DNA repair activity in a host cell reactivation (HCR) assay. In contrast, in
      cells from three mildly affected siblings in family B, the BPS adenosine located
      at the -24 position in XPC intron 3 is mutated to a G. Real-time QRT-PCR revealed
      3-5% of normal XPC message. These cells from family B had a higher level of HCR
      than cells from the severely affected siblings in family A, who had multiple skin
      cancers. Mutations identified in two BPS of the XPC intron 3 resulted in
      alternative splicing that impaired DNA repair function, thus implicating both of
      these BPS as essential for normal pre-mRNA splicing. However, a small amount of
      normal XPC mRNA can provide partial protection against skin cancers.

PMID- 14662656
TI  - Mitochondrial complex I mutations in Caenorhabditis elegans produce cytochrome c
      oxidase deficiency, oxidative stress and vitamin-responsive lactic acidosis.
AB  - Mitochondrial dysfunction, with an estimated incidence of 1 in 10 000 live
      births, is among the most common genetically determined conditions. Missense
      mutations in the human NDUFV1 gene, which encodes the 51 kDa active site subunit
      of the NADH-ubiquinone oxidoreductase or complex I, can lead to severe
      neurological disorders. Owing to the rare and often sporadic nature of
      mitochondrial disorders, the mechanisms of pathogenesis of most mutations remain
      poorly understood. We have generated transgenic strains of Caenorhabditis elegans
      that express disease-causing mutations in the nuo-1 gene, the C. elegans homolog
      of the NDUFV1 gene. The transgenic strains demonstrate hallmark features of
      complex I dysfunction such as lactic acidosis and decreased NADH-dependent
      mitochondrial respiration. They are also hypersensitive to exogenous oxidative
      stress, suggesting that cellular defense mechanisms against reactive oxygen
      species are already taxed by an endogenous stress. The lactic acidosis induced by
      the NDUFV1 mutations could be partially corrected with the vitamins riboflavin
      and thiamine or with sodium dichloroacetate, an activator of the pyruvate
      dehydrogenase complex, resulting in significant increases in animal fitness.
      Surprisingly, cytochrome c oxidase activity and protein levels were reduced,
      establishing a connection between complexes I and IV. Our results indicate that
      complex I mutations exert their pathogenic effects in multiple ways: by impeding
      the metabolism of NADH, by increasing the production of reactive oxygen species,
      and by interfering with the function or assembly of other mitochondrial
      respiratory chain components.

PMID- 14662657
TI  - Expression of complement components in the peripheral nervous system.
AB  - We have generated a SAGE (serial analysis of gene expression) library of normal
      sciatic nerve and found tags encoding for mRNAs of the complement system highly
      represented. RNA (RT-PCR and northern blot hybridization) and protein (western
      blot analysis and immunohistochemistry) studies confirmed these findings. High
      expression of classical pathway components, alternative pathway components and
      inhibitory components was observed in specific regions of the sciatic nerve. The
      first components of complement were found in axons, whereas the inhibitory
      components were detected in the perineurium, thereby protecting the nerve from a
      complement attack. Immunoreactivity towards activated complement factors was
      noted in post traumatic neuromas and after acute crush injury, which exemplify
      nerve regeneration and degeneration. We propose that local production of
      complement in the peripheral nervous system participates in the protection of
      healthy nerve and is needed for efficient clearance of myelin after injury: a
      prerequisite for normal regeneration and remyelination of the peripheral nerve.

PMID- 14662658
TI  - Patently necessary: improving global access to essential medicines.

PMID- 14662661
TI  - Are hot tubs safe for people with treated hypertension?
AB  - BACKGROUND: People with hypertension are commonly warned to check with a
      physician before using a hot tub, but there is little literature on which to base
      this advice. We compared symptoms, heart rate, and systolic and diastolic blood
      pressure in response to 10 minutes of hot-tub immersion in a group of patients
      with treated hypertension and in a control group normotensive subjects. METHODS:
      We recruited 21 patients (18 men and 3 women aged 43-76 years) with stable,
      treated hypertension and 23 control subjects (14 men and 9 women aged 19-83
      years) without hypertension. They were studied, in mid-afternoon, at a public
      facility. Systolic and diastolic blood pressure and heart rate were measured at
      baseline, during immersion in a hot tub at 40 degrees C and for 10 minutes after
      immersion. We asked each subject to report any symptoms. RESULTS: None of the
      subjects reported dizziness, chest pain or palpitations. During immersion,
      systolic blood pressure fell in both groups, from a mean (and standard deviation
      [SD]) of 144 (17) mm Hg to 122 (18) mm Hg in the hypertensive group (p < 0.05)
      and from 130 (14) mm Hg to 110 (17) mm Hg in the control group (p < 0.05). It
      returned toward baseline within 10 minutes after the subjects left the hot tub.
      Diastolic blood pressure also fell, whereas heart rate was increased in both
      groups. The hypertensive group showed a slightly lower maximal increase in heart
      rate than the normotensive group (5 [SD 5] v. 13 [SD 10] beats/minute, p < 0.05).
      INTERPRETATION: Immersion in a hot tub for 10 minutes lowers blood pressure in
      subjects with treated hypertension, but no more than in normotensive control
      subjects. Spending 10 minutes in a hot tub should be safe for most treated
      hypertensive patients.

PMID- 14662662
TI  - Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a
      randomized controlled trial.
AB  - BACKGROUND: Extract of globe artichoke (Cynara scolymus) is promoted as a
      possible preventive or cure for alcohol-induced hangover symptoms. However, few
      rigorous clinical trials have assessed the effects of artichoke extract, and none
      has examined the effects in relation to hangovers. We undertook this study to
      test whether artichoke extract is effective in preventing the signs and symptoms
      of alcohol-induced hangover. METHODS: We recruited healthy adult volunteers
      between 18 and 65 years of age to participate in a randomized double-blind
      crossover trial. Participants received either 3 capsules of commercially
      available standardized artichoke extract or indistinguishable, inert placebo
      capsules immediately before and after alcohol exposure. After a 1-week washout
      period the volunteers received the opposite treatment. Participants predefined
      the type and amount of alcoholic beverage that would give them a hangover and ate
      the same meal before commencing alcohol consumption on the 2 study days. The
      primary outcome measure was the difference in hangover severity scores between
      the artichoke extract and placebo interventions. Secondary outcome measures were
      differences between the interventions in scores using a mood profile
      questionnaire and cognitive performance tests administered 1 hour before and 10
      hours after alcohol exposure. RESULTS: Fifteen volunteers participated in the
      study. The mean number (and standard deviation) of alcohol units (each unit being
      7.9 g, or 10 mL, of ethanol) consumed during treatment with artichoke extract and
      placebo was 10.7 (3.1) and 10.5 (2.4) respectively, equivalent to 1.2 (0.3) and
      1.2 (0.2) g of alcohol per kilogram body weight. The volume of nonalcoholic drink
      consumed and the duration of sleep were similar during the artichoke extract and
      placebo interventions. None of the outcome measures differed significantly
      between interventions. Adverse events were rare and were mild and transient.
      INTERPRETATION: Our results suggest that artichoke extract is not effective in
      preventing the signs and symptoms of alcohol-induced hangover. Larger studies are
      required to confirm these findings.

PMID- 14662663
TI  - Words used by children and their primary caregivers for private body parts and
      functions.
AB  - BACKGROUND: Effective patient-physician communication requires the use of words
      that are clearly understood by both parties. We conducted this study to compile a
      list of words used by children and caregivers to describe "private" anatomical
      structures and physiological functions, to document the frequency of such usage
      and to examine the relation between correct word usage and caregiver's level of
      education. METHODS: In a large urban pediatric emergency department, a
      convenience sample of 156 children at least 3 years old were asked to name the
      body parts (penis, testes, vagina, buttocks, breasts) pointed to in 4 simple,
      explicit line drawings of an unclothed boy or girl, and to name the bodily
      functions (vomiting, defecation, urination) depicted in 3 drawings of children.
      Eighty-seven patients sufficiently fluent in English were included in the study.
      Their caregivers were asked separately what words they currently use with their
      child and with other adults for these body parts and functions and what words
      they remembered using as children. RESULTS: The children used a mean of 1.2
      correct anatomical and physiological terms out of a possible 8 to describe the
      private parts and functions in the drawings. The mean number of correct words
      used by the caregivers was 2.3 when talking with their children, 3.6 when talking
      with their peers and 1.5 when they were children. There was no correlation
      between the caregiver's level of education and the frequency of correct word
      usage by their children. We identified slang words used by at least 5% of the
      respondents; however, some used the same slang words to refer to different body
      parts. INTERPRETATION: Given the variety of slang words used by children and
      their caregivers to describe private parts and functions, the meaning of the
      words should be clarified during history taking.

PMID- 14662664
TI  - The new normal: a SARS diary.

PMID- 14662665
TI  - My experience with SARS.

PMID- 14662666
TI  - Worry.

PMID- 14662667
TI  - Effect of colour coordination of attire with poster presentation on poster
      popularity.

PMID- 14662668
TI  - A modest proposal to meet our Kyoto commitments: the answer lies within.

PMID- 14662669
TI  - Head injuries in nursery rhymes: evidence of a dangerous subtext in children's
      literature.

PMID- 14662670
TI  - Understanding the number of copies of ethics applications required by faculties
      of medicine.

PMID- 14662671
TI  - Nepal: a lesson from chaos.

PMID- 14662672
TI  - Experience at the Arctic Bay Nursing Station on the coast of Baffin Island.

PMID- 14662673
TI  - Pathologists going "live": lessons from a developing country on giving a human
      face to pathology.

PMID- 14662674
TI  - It's tradition.

PMID- 14662675
TI  - Incognito.

PMID- 14662676
TI  - Diary of an ICU slave.

PMID- 14662677
TI  - Misplaced.

PMID- 14662678
TI  - Ward teaching (dys)connections.

PMID- 14662679
TI  - "She left a sizable RRSP".

PMID- 14662680
TI  - Eating healthy.

PMID- 14662681
TI  - How to read clinical journals: XI. Everything you always wanted to know about
      editorials (but were afraid to ask).

PMID- 14662682
TI  - MDs 'R' Us: holiday ideas for that special physician:.

PMID- 14662684
TI  - A life insurance medical, 1848.

PMID- 14662683
TI  - Days of shame, Montreal, 1934.

PMID- 14662685
TI  - "That will be $231, please".

PMID- 14662686
TI  - Turf war: medical men take on the establishment in Niagara Falls, Ontario.

PMID- 14662688
TI  - Selecting the best reperfusion strategy in ST-elevation myocardial infarction:
      it's all a matter of time.

PMID- 14662689
TI  - Are stenting and glycoprotein IIb/IIIa blockade of good value in primary
      percutaneous coronary intervention?

PMID- 14662690
TI  - Acute pulmonary embolism: part II: risk stratification, treatment, and
      prevention.

PMID- 14662691
TI  - Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus
      statement from the American Heart Association and American Diabetes Association.
      October 7, 2003.

PMID- 14662692
TI  - Images in cardiovascular medicine. Hughes-Stovin syndrome.

PMID- 14662693
TI  - Bosentan and overcirculation-induced experimental pulmonary arterial
      hypertension.

PMID- 14662694
TI  - Tako-tsubo-like left ventricular dysfunction.

PMID- 14662695
TI  - Prosthetic heart valves and pregnancy.

PMID- 14662696
TI  - Coronary collaterals.

PMID- 14662697
TI  - The obsession with primary angioplasty.

PMID- 14662698
TI  - Human aortic valve calcification.

PMID- 14662699
TI  - Peripheral adiposity and cardiovascular risk.

PMID- 14662700
TI  - Determining the "CADILLAC" of care.

PMID- 14662701
TI  - Circumstances of death and gross and microscopic observations in a series of 200
      cases of sudden death associated with arrhythmogenic right ventricular
      cardiomyopathy and/or dysplasia.
AB  - BACKGROUND: Sudden death is a possible consequence of arrhythmogenic right
      ventricular cardiomyopathy/dysplasia (ARVC/D). Prevalence of ARVC/D in unexpected
      sudden cardiac death (USCD), however, remains imprecise, as do circumstances of
      death and ARVC/D-associated gross and microscopic findings, especially His bundle
      anomalies. METHODS AND RESULTS: We reviewed 14 000 forensic autopsies required by
      judicial authorities from January 1980 to January 1999 in a 2 000 000-resident
      area. Age, gender, and circumstances of death were recorded. Hearts were examined
      macroscopically and microscopically. In this series, the ARVC/D group accounted
      for 200 consecutive cases (10.4%) of USCD, including 108 males and 92 females
      (average age 32.5 and 34.5 years, respectively). Nearly one third of deaths
      occurred during the fourth decade of life. Circumstances of death were various,
      but 75.6% occurred during everyday life events (at home, 63.1%; in the street,
      6.6%; or at work, 6.1%); only 7 cases (3.5%) occurred during sports activity.
      Nineteen cases (9.5%) happened during the perioperative period. Adipose
      infiltration of the right ventricle was either isolated (20%) or associated with
      fibrosis (74.5%) and lymphocytes (5.5%). A total of 14.5% of cases had cardiac
      hypertrophy, assessed by an increase in heart weight and/or left ventricular wall
      thickness. In most cases, the His bundle and its branches were abnormal either
      because of infiltration of adipose tissue (8.1%), fibrosis (54.3%), or both
      (5.6%). CONCLUSIONS: In ARVC/D, both sexes are equally affected, and there is a
      peak of risk during the fourth decade. Death most frequently occurs during
      sedentary activity. His abnormalities and left ventricular hypertrophy may be
      associated with ARVC/D.

PMID- 14662702
TI  - P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control
      study.
AB  - BACKGROUND: We recently described a gain-of-function haplotype, called H2, of the
      adenosine diphosphate (ADP) receptor P2Y12 gene associated with increased ADP
      induced platelet aggregation ex vivo in healthy volunteers. Because platelets
      play a key role in atherosclerosis and arterial thrombosis, we tested the
      possible link between the H2 haplotype and the risk of peripheral arterial
      disease (PAD) in a case-control study. METHODS AND RESULTS: We studied 184
      consecutive male patients under 70 years of age with PAD and 330 age-matched
      control subjects free of symptomatic PAD and with no cardiovascular history. Mean
      age was 57.1+/-7.2 years (cases) and 56.7+/-7.6 years (control subjects). The H2
      haplotype was more frequent in patients with PAD than in control subjects (30%
      and 21%, respectively; OR, 1.6; CI, 1.1 to 2.5; P=0.02 in univariate analysis).
      This association with PAD remained significant in multivariate regression
      analysis (OR, 2.3; CI, 1.4 to 3.9; P=0.002) after adjustment for diabetes,
      smoking, hypertension, hypercholesterolemia, and other selected platelet receptor
      gene polymorphisms. CONCLUSIONS: These data point to a role of the H2 haplotype
      in atherosclerosis and raise the possibility of relative thienopyridine
      resistance in carriers of the P2Y12 H2 haplotype.

PMID- 14662703
TI  - Plasma B-type natriuretic peptide levels in ambulatory patients with established
      chronic symptomatic systolic heart failure.
AB  - BACKGROUND: The diagnostic and prognostic values of plasma B-type natriuretic
      peptide (BNP) testing are established. However, the range of plasma BNP levels
      present in the setting of chronic, stable systolic heart failure (HF) is unclear.
      METHODS AND RESULTS: We followed up 558 consecutive ambulatory patients with
      chronic, stable systolic HF (left ventricular ejection fraction <50%) treated at
      a specialized outpatient HF clinic between November 2001 and February 2003.
      Retrospective chart review was performed to determine clinical and functional
      data at the time of BNP testing (Biosite Triage). The clinical characteristics of
      patients with plasma BNP levels <100 pg/mL and those with > or =100 pg/mL were
      compared. In our cohort, 60 patients were considered asymptomatic, and their
      plasma BNP levels ranged from 5 to 572 pg/mL (median, 147 pg/mL). Of the
      remaining 498 symptomatic (NYHA functional class II-III) patients, 106 (21.3%)
      had plasma BNP levels in the "normal" diagnostic range (<100 pg/mL). Patients in
      this "normal BNP" subgroup were more likely to be younger, to be female, to have
      nonischemic pathogenesis, and to have better-preserved cardiac and renal function
      and less likely to have atrial fibrillation. CONCLUSIONS: In the ambulatory care
      setting, both symptomatic and asymptomatic patients with chronic, stable systolic
      HF may present with a wide range of plasma BNP levels. In a subset of symptomatic
      patients (up to 21% in our cohort), plasma BNP levels are below what would be
      considered "diagnostic" (<100 pg/mL).

PMID- 14662704
TI  - Percutaneous endovascular repair of aneurysm after previous coarctation surgery.
AB  - BACKGROUND: Formation of aortic aneurysm late after surgical repair of
      coarctation carries a significant risk of rupture and lethal outcome, and repeat
      surgery is associated with a 14% in-hospital mortality rate and morbidity from
      paraplegia, injury to the central nervous system, or from bleeding. The potential
      of nonsurgical endovascular repair by the use of stent-grafts in lieu of repeat
      surgery for postcoarctation aneurysm is unknown. METHODS AND RESULTS: The concept
      of postsurgical endovascular stent-graft placement was evaluated with respect to
      feasibility and safety in 6 consecutive patients with late aneurysm formation
      after coarctation repair. All patients had aneurysm formation late after patch
      aortoplasty; placement of an elephant trunk during surgical repair of secondary
      type I dissection preceded formation of a local aneurysm in 2 cases. Patient age
      was 49+/-12 years, ranging from 31 to 68 years. Transluminal placement of
      customized stent-grafts was successful, with no 30-day or 1-year intervention
      related mortality or morbidity. Follow-up survey of 11 to 47 months revealed
      optimal reconstruction of the thoracic aorta; 1 patient died 11 months after
      endovascular repair from cancer. CONCLUSIONS: Nonsurgical aortic reconstruction
      of postsurgical thoracic aneurysms forming late after coarctation repair is safe
      and feasible; interventional stent-graft placement has the potential to avoid
      repeat surgery of postsurgical aortic aneurysm.

PMID- 14662705
TI  - Methoxyestradiols mediate the antimitogenic effects of 17beta-estradiol: direct
      evidence from catechol-O-methyltransferase-knockout mice.
AB  - BACKGROUND: Studies using pharmacological agents suggest but do not prove that
      the antimitogenic effects of estradiol are caused by conversion of estradiol to
      hydroxyestradiols (mediated by CYP450s) followed by methylation of
      hydroxyestradiols to methoxyestradiols (mediated by catechol-O-methyltransferase,
      COMT). METHODS AND RESULTS: To test this hypothesis more rigorously, we used
      aortic smooth muscle cells (SMCs) from mice lacking COMT (COMT-KO). Wild-type
      (WT) but not COMT-KO SMCs efficiently converted 2-hydroxyestradiol to 2
      methoxyestradiol. Both WT and COMT-KO SMCs expressed estrogen receptors.
      Estradiol and 2-hydroxyestradiol concentration-dependently inhibited serum
      induced DNA synthesis, cell numbers, and collagen synthesis in WT but not COMT-KO
      SMCs. 2-Methoxyestradiol inhibited DNA synthesis, cell numbers, and collagen
      synthesis in both WT and COMT-KO SMCs. CONCLUSIONS: These data provide strong
      evidence that the vascular antimitogenic effects of estradiol are estrogen
      receptor-independent and involve the sequential conversion of estradiol to
      hydroxyestradiols and then to methoxyestradiols.

PMID- 14662706
TI  - Arterial stiffness, wave reflections, and the risk of coronary artery disease.
AB  - BACKGROUND: Increased arterial stiffness, determined invasively, has been shown
      to predict a higher risk of coronary atherosclerosis. However, invasive
      techniques are of limited value for screening and risk stratification in larger
      patient groups. METHODS AND RESULTS: We prospectively enrolled 465 consecutive,
      symptomatic men undergoing coronary angiography for the assessment of suspected
      coronary artery disease. Arterial stiffness and wave reflections were quantified
      noninvasively using applanation tonometry of the radial artery with a validated
      transfer function to generate the corresponding ascending aortic pressure
      waveform. Augmented pressure (AP) was defined as the difference between the
      second and the first systolic peak, and augmentation index (AIx) was AP expressed
      as a percentage of the pulse pressure. In univariate analysis, a higher AIx was
      associated with an increased risk for coronary artery disease (OR, 4.06 for the
      difference between the first and the fourth quartile [1.72 to 9.57; P<0.01]). In
      multivariate analysis, after controlling for age, height, presence of
      hypertension, HDL cholesterol, and medications, the association with coronary
      artery disease risk remained significant (OR, 6.91; P<0.05). The results were
      exclusively driven by an increase in risk with premature vessel stiffening in the
      younger patient group (up to 60 years of age), with an unadjusted OR between AIx
      quartiles I and IV of 8.25 (P<0.01) and a multiple-adjusted OR between these
      quartiles of 16.81 (P<0.05). CONCLUSIONS: AIx and AP, noninvasively determined
      manifestations of arterial stiffening and increased wave reflections, are strong,
      independent risk markers for premature coronary artery disease.

PMID- 14662707
TI  - Hostile behaviors predict cardiovascular mortality among men enrolled in the
      Multiple Risk Factor Intervention Trial.
AB  - BACKGROUND: Hostility is associated with incident coronary disease in most large
      population-based studies, but little is known about its association with
      cardiovascular disease (CVD) mortality in high-risk individuals. The aim of this
      study was to assess the association of hostility with CVD mortality in the
      subsequent 16 years in the Multiple Risk Factor Intervention Trial (MRFIT)
      participants and to explore the influence of hostility in the subset that had a
      nonfatal CVD event during the trial. METHODS AND RESULTS: We coded the Structured
      Interview responses of 259 men who died of CVD during the 16 years of follow-up
      and 259 matching living control subjects. Signs of hostility were assessed by use
      of the Interpersonal Hostility Assessment Technique. Matching was based on
      center, intervention group, age, race, and interviewer; covariates included study
      entry diastolic blood pressure, cholesterol, smoking status, and nonfatal CVD
      event during the trial. High-hostile men were more likely to die of CVD than were
      low-hostile men. Adjusted odds ratio (OR) and 95% confidence intervals (CIs) were
      1.61, 1.09 to 2.39. After the trial, high-hostile men who also had a nonfatal
      event during the trial were particularly likely to die of CVD, OR, 5.06, 1.42 to
      8.22, compared with low-hostile men without a nonfatal event during the trial.
      CONCLUSIONS: Hostility may be a risk factor for CVD mortality among high-risk
      men. Interventions aimed at anger management and stress reduction along with risk
      factor modification may be useful for hostile patients.

PMID- 14662708
TI  - Cardiovascular effects of systemic nitric oxide synthase inhibition with
      asymmetrical dimethylarginine in humans.
AB  - BACKGROUND: Increased blood concentrations of the endogenous nitric oxide
      synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) have been linked to
      excess cardiovascular morbidity and mortality and to progression of renal
      disease. We evaluated systemic cardiovascular effects of ADMA infusion in healthy
      subjects using invasive techniques, ie, right heart catheter and inulin/para
      aminohippurate clearance. METHODS AND RESULTS: Plasma ADMA concentrations
      encountered in patients with cardiovascular diseases, ie, between 2 and 10
      micromol/L, caused a significant (P<0.05) decrease in concentrations of plasma
      cGMP, the main second messenger of NO. In addition, cardiac output was
      significantly lower (5.3+/-0.4 versus 5.8+/-0.6 L/min; P<0.05 versus baseline),
      and systemic vascular resistance was significantly higher (1403+/-123 versus
      1221+/-100 dyn x s x cm(-5); P<0.05 versus baseline). The infusion of 0.25 mg
      ADMA x kg(-1) x min(-1) or 3 microg N(G)-nitro-L-arginine methyl ester x kg(-1) x
      min(-1), a potent synthetic NOS inhibitor with long action, resulted in a
      comparable decrease in effective renal plasma flow (from 670+/-40 to 596+/-29 mL
      x min(-1); P<0.05) and an increase in renovascular resistance (from 79+/-5 to
      90+/-7 mm Hg x mL(-1) x min(-1); P<0.05). Moreover, administration of ADMA caused
      significant sodium retention and blood pressure increase (both P<0.05). The
      observed effects of ADMA in the systemic circulation were sustained corresponding
      to a mean plasma half-life of 23.5+/-6.8 minutes, calculated from plasma ADMA
      decay curves in healthy subjects. CONCLUSIONS: Systemic ADMA infusion is
      responsible for a short-term, modest decrease in cardiac output with comparable
      decrease in effective renal plasma flow while increasing systemic vascular
      resistance and blood pressure in a dose-related manner.

PMID- 14662709
TI  - Inhibition of cytochrome P450 2C9 improves endothelium-dependent, nitric oxide
      mediated vasodilatation in patients with coronary artery disease.
AB  - BACKGROUND: Nitric oxide (NO)- and prostacyclin-independent vasodilatation in
      several vascular beds has been linked to the activation of cytochrome P450 (CYP)
      epoxygenases expressed in endothelial cells. However, these enzymes, which
      generate vasodilator epoxyeicosatrienoic acids, may also produce oxygen-derived
      free radicals, which attenuate the bioavailability of NO. Here, we studied the
      involvement of CYP 2C9 in modulating endothelium-dependent and -independent
      changes in forearm blood flow (FBF) in healthy volunteers and in patients with
      manifest coronary artery disease. METHODS AND RESULTS: The effects of
      sulfaphenazole, a selective inhibitor of CYP 2C9, on endothelium-dependent
      (acetylcholine) and endothelium-independent (sodium nitroprusside, SNP) FBF
      responses were measured by venous occlusion plethysmography in 5 healthy subjects
      and in 16 patients with angiographically documented stable coronary artery
      disease. Sulfaphenazole did not modify FBF responses to acetylcholine or SNP in
      healthy subjects. In contrast, sulfaphenazole markedly and dose-dependently
      enhanced the FBF response to acetylcholine without affecting the response to SNP.
      Vitamin C also increased the FBF response to acetylcholine, but this effect was
      further potentiated by sulfaphenazole. In the presence of N(omega)-monomethyl-l
      arginine, sulfaphenazole failed to significantly improve acetylcholine-induced
      vasodilatation. The oxidation of serum proteins was enhanced in patients with
      coronary artery disease, and this effect was significantly attenuated by
      sulfaphenazole. CONCLUSIONS: The CYP 2C9 inhibitor sulfaphenazole enhances
      endothelium-dependent vasodilator responses in patients with manifest coronary
      artery disease. This effect seems to be related to an increase in the
      bioavailability of NO, probably as a consequence of an attenuated generation of
      reactive oxygen species by CYP 2C9 in endothelial cells.

PMID- 14662710
TI  - Mechanism of ST elevation and ventricular arrhythmias in an experimental Brugada
      syndrome model.
AB  - BACKGROUND: Although phase 2 reentry is said to be responsible for initiation of
      ventricular tachycardia (VT) in Brugada syndrome, information about the
      activation sequence during VT is limited. METHODS AND RESULTS: We developed an
      experimental Brugada syndrome model using a canine isolated right ventricular
      preparation cross-circulated with arterial blood of a supporter dog and examined
      the VT mechanism. Two plaque electrodes (35x30 mm) containing 96 bipolar
      electrodes were attached to the endocardium and epicardium. Saddleback and coved
      types of ST elevation in transmural ECG were induced by pilsicainide, a pure
      sodium channel blocker, and pinacidil, a KATP channel opener. Eighteen
      polymorphic VT episodes were recorded in 9 of the 12 preparations associated with
      ST elevation. Fourteen episodes spontaneously developed in 5 preparations after
      an extrasystole during basic drive pacing. Analysis of local recovery times
      revealed increased dispersion especially in epicardium, and the extrasystole
      originated from a site with a short recovery time, suggesting that phase 2
      reentry was its mechanism. The other 4 VTs in 4 preparations were induced by
      premature stimulation. Analysis of the activation sequences during VT revealed
      reentry between epicardium and endocardium or reentry around an arc of a
      functional block confined to epicardium or endocardium with bystander activation
      of the other. CONCLUSIONS: Electrical heterogeneity in the recovery phase was
      induced in this experimental Brugada syndrome model, which can be a substrate for
      the development of phase 2 reentry and the subsequent reentry around an arc of
      the functional block, resulting in sustained VT.

PMID- 14662711
TI  - Chronic infusion of bradykinin delays the progression of heart failure and
      preserves vascular endothelium-mediated vasodilation in conscious dogs.
AB  - BACKGROUND: This study examined the effects of chronic bradykinin infusion on
      hemodynamics and myocardial and endothelial functions during the development of
      heart failure. METHODS AND RESULTS: Sixteen instrumented dogs were randomized to
      receive through the left atria either vehicle or bradykinin (1 microg/min) during
      ventricular pacing (250 bpm, 5 weeks). Hemodynamic and left ventricular (LV)
      parameters and the vasodilator responses to intravenous acetylcholine (0.3 to 3
      microg/kg) and nitroglycerin (1 to 10 microg/kg) were examined in the control and
      after 3 and 5 weeks of pacing. The expression of endothelial NOS in femoral,
      carotid, and renal arteries was determined by Western blot analysis. After 3
      weeks of pacing, changes in LV diastolic and systolic parameters were
      significantly lower in bradykinin-treated than vehicle-treated dogs (LV end
      diastolic pressure, +10+/-3 versus +19+/-2 mm Hg; time constant of LV isovolumic
      relaxation, +11+/-2 versus +17+/-1 ms; LV wall thickening, -33+/-18% versus -75+/
      9%; and cardiac output, -16+/-6% versus -32+/-6%; all P<0.05). Compared with
      vehicle-treated dogs, bradykinin-treated dogs had a reduced rightward shift of
      the diastolic LV pressure-diameter relation and a reduced diastolic LV wall
      stress. Similar trends were observed after 5 weeks. The vasodilator response to
      nitroglycerin was preserved in both groups. The response to acetylcholine was
      blunted in vehicle-treated but preserved in bradykinin-treated dogs. Vascular
      endothelial NOS expression decreased in vehicle-treated but was preserved in
      bradykinin-treated dogs. CONCLUSIONS: In conscious dogs, chronic bradykinin
      infusion delays the heart failure progression by preserving LV diastolic and
      systolic functions and by preserving vascular endothelial function.

PMID- 14662712
TI  - Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy
      oligodeoxynucleotides suppressing activity of nuclear factor kappaB and ets
      transcription factors.
AB  - BACKGROUND: Two phenomena, inflammation and matrix degradation, contribute to the
      progression of abdominal aortic aneurysm (AAA). Importantly, the inflammation is
      regulated by the transcription factor nuclear factor (NF)-kappaB, whereas the
      destruction and degradation of elastin fibers by matrix metalloproteinases (MMP)
      are regulated by ets. Thus, we developed a novel strategy to treat AAA by
      simultaneous inhibition of both NF-kappaB and ets by using chimeric decoy
      oligodeoxynucleotides (ODN). METHODS AND RESULTS: AAA was induced in rats by
      transient aortic perfusion with elastase, whereas transfection of decoy ODN was
      performed by wrapping a delivery sheet containing decoy ODN around the aorta. Gel
      mobility shift assay at 7 days after treatment demonstrated that both NF-kappaB
      and ets binding activity were simultaneously inhibited by chimeric decoy ODN.
      Transfection of chimeric decoy ODN resulted in significant inhibition of the
      progression of AAA such as aneurysmal dilation at 4 weeks after treatment as
      compared with control, accompanied by a reduction of MMP expression. Moreover,
      the destruction of elastin fibers was inhibited in the aorta transfected with
      chimeric decoy ODN. Importantly, transfection of chimeric decoy ODN demonstrated
      potent inhibition of aneurysmal dilatation compared with NF-kappaB decoy ODN
      alone, whereas scrambled decoy ODN had no effects. Interestingly, the migration
      of macrophages was significantly inhibited by chimeric decoy ODN. CONCLUSIONS: We
      demonstrated that inhibition of the progression of AAA was achieved by a novel
      strategy with chimeric decoy ODN used against NF-kappaB and ets in rat model. NF
      kappaB and ets are considered to play an important role in the pathogenesis of
      AAA.

PMID- 14662713
TI  - Antirestenotic effects of a locally delivered caspase inhibitor in a balloon
      injury model.
AB  - BACKGROUND: The precise role of arterial barotrauma-mediated apoptosis in causing
      restenosis is unclear. The purpose of this study was to determine if a link
      exists between angioplasty-mediated medial smooth muscle cell apoptosis and
      subsequent neointimal hyperplasia. METHODS AND RESULTS: Bilateral iliac artery
      angioplasty was performed in 25 male New Zealand White rabbits. Simultaneous with
      balloon injury, each artery was treated locally with either the caspase inhibitor
      N-benzyloxycarbonyl-Val-Ala-Asp(Ome)-fluoromethylketone (ZVAD-fmk) or control. In
      the acute cohort that was survived to 4 hours (n=10, 7 high dose and 3 low dose),
      an apoptotic index was calculated using the terminal deoxynucleotidyl TUNEL
      method. In the intermediate cohort that was survived to 2 weeks (n=5), luminal
      reendothelialization was measured via CD-31 staining. In the chronic cohort that
      was survived to 4 weeks (n=10), neointimal area was measured. In the acute
      cohort, there was a 40% reduction in the apoptotic index with high-dose ZVAD-fmk
      (P=0.008) and a 33% reduction with low-dose ZVAD-fmk (P=0.08). At 2 weeks, there
      was no significant difference in the degree of luminal reendothelialization.
      However, at 4 weeks, there was a 33% (0.33+/-0.23 versus 0.22+/-0.20 mm2)
      (P<0.005) reduction in neointimal area in ZVAD-fmk-treated arteries. CONCLUSIONS:
      The local delivery of ZVAD-fmk during balloon injury inhibits smooth muscle cell
      apoptosis. This corresponds to a significant reduction in neointimal
      proliferation seen at 4 weeks without a significant change in the degree of
      reendothelialization at 2 weeks.

PMID- 14662714
TI  - Vagal nerve stimulation markedly improves long-term survival after chronic heart
      failure in rats.
AB  - BACKGROUND: Diminished cardiac vagal activity and higher heart rate predict a
      high mortality rate of chronic heart failure (CHF) after myocardial infarction.
      We investigated the effects of chronic electrical stimulation of the vagus nerve
      on cardiac remodeling and long-term survival in an animal model of CHF after
      large myocardial infarction. METHODS AND RESULTS: Two weeks after the ligation of
      the left coronary artery, surviving rats were randomized to vagal- and sham
      stimulated groups. Using an implantable miniature radio-controlled electrical
      stimulator, we stimulated the right vagal nerve of CHF rats for 6 weeks. The
      intensity of electrical stimulation was adjusted for each rat, so that the heart
      rate was lowered by 20 to 30 beats per minute. The treated rats had significantly
      lower left ventricular end-diastolic pressure (17.1+/-5.9 versus 23.5+/-4.2 mm
      Hg, P<0.05) and higher maximum dp/dt of left ventricular pressure (4152+/-237
      versus 2987+/-192 mm Hg/s, P<0.05) than the untreated rats. Improvement of
      cardiac pumping function was accompanied by a decrease in normalized
      biventricular weight (2.75+/-0.25 versus 3.14+/-0.22 g/kg, P<0.01). Although the
      140-day survival of the untreated group was only half, vagal stimulation markedly
      improved the survival rate (86% versus 50%, P=0.008). Vagal stimulation therapy
      achieved a 73% reduction in a relative risk ratio of death. CONCLUSIONS: Vagal
      nerve stimulation markedly improved the long-term survival of CHF rats through
      the prevention of pumping failure and cardiac remodeling.

PMID- 14662715
TI  - Genetically reduced antioxidative protection and increased ischemic heart disease
      risk: The Copenhagen City Heart Study.
AB  - BACKGROUND: Extracellular superoxide dismutase (EC-SOD) is an antioxidative
      enzyme found in high concentrations in the arterial wall. Two to three percent of
      all people in Denmark carry an R213G substitution, which increases plasma
      concentration 10-fold. This may reduce arterial wall EC-SOD concentrations,
      increase intimal LDL oxidation, and therefore may accelerate atherogenesis. Our
      primary hypothesis was that EC-SOD-R213G predisposes to ischemic heart disease
      (IHD). The secondary hypothesis was that EC-SOD-R213G offers predictive ability
      with respect to IHD beyond that offered by measurements of plasma EC-SOD and
      autoantibodies against oxidized LDL (oxLDL). METHODS AND RESULTS: The primary
      hypothesis was tested in a prospective, population-based study of 9188
      participants from The Copenhagen City Heart Study with 956 incident IHD events
      during 23 years of follow-up and retested cross-sectionally with independent case
      populations of patients with IHD (n=943) or ischemic cerebrovascular disease
      (ICVD) (n=617). Case populations were compared with unmatched IHD/ICVD-free
      control subjects from The Copenhagen City Heart Study (n=7992). The secondary
      hypothesis was tested by using a nested case-control study comparing patients
      with IHD (n=956) with age- and gender-matched control subjects (n=956). Age- and
      gender-adjusted relative risk for IHD in heterozygotes (n=221, 2.4%) versus
      noncarriers (n=8965, 97.6%) was 1.5 (95% CI, 1.1 to 2.1). Retesting confirmed
      this: Age- and gender-adjusted odds ratios for IHD was 1.4 (1.0 to 2.0) and for
      ICVD 1.7 (1.1 to 2.7). Additional adjustment for plasma EC-SOD produced an odds
      ratio for IHD in heterozygotes versus noncarriers of 9.2 (1.2 to 72), whereas
      adjustment for autoantibodies against oxLDL produced an odds ratio of 2.5 (1.2 to
      5.3). CONCLUSIONS: Heterozygosity for EC-SOD-R213G is associated with increased
      IHD risk. Genotyping offers predictive ability with respect to IHD beyond that
      offered by plasma EC-SOD and autoantibodies against oxLDL.

PMID- 14662716
TI  - Nitric oxide and beta-adrenergic stimulation are major regulators of preprandial
      and postprandial subcutaneous adipose tissue blood flow in humans.
AB  - BACKGROUND: Blood flow mediates the metabolic and endocrine roles of adipose
      tissue. We have previously shown that the postprandial adipose tissue blood flow
      (ATBF) increase is dependent on insulin sensitivity. However, subcutaneous local
      insulin delivery had no demonstrable effect on either preprandial or postprandial
      ATBF. We hypothesized that insulin may act indirectly via sympathetic activation,
      mainly in the postprandial period, and that nitric oxide may be an overall major
      regulator of subcutaneous ATBF. METHODS AND RESULTS: We investigated the
      endogenous preprandial and postprandial regulation of ATBF by applying local
      tissue blockade of beta-adrenergic (propranolol), alpha-adrenergic (phentolamine
      and yohimbine), and nitric oxide (NG-monomethyl-L-arginine, L-NMMA) regulation of
      blood flow. Healthy subjects (body mass index, 18 to 31 kg/m2) were challenged
      with 75 g glucose for endogenous stimulation of ATBF. We used the novel
      "microinfusion" technique, which allows for simultaneous local delivery of
      pharmacological agents (or contralateral saline) and measurement of ATBF with the
      133Xe washout method. Compared with control, the preprandial ATBF was not
      affected by propranolol but was increased by 21% (P<0.013) and 15% (P=0.004) with
      phentolamine and yohimbine, respectively. A decrease of 42% (2.97+/-0.33 versus
      4.75+/-0.47 mL x min(-1) x 100 g tissue(-1), P<0.01) was seen with L-NMMA. The
      postprandial response was blunted by 58% (0.81+/-0.42 versus 1.90+/-0.44 mL x
      min(-1) x 100 g tissue(-1), P<0.004) with propranolol, but neither phentolamine,
      yohimbine, or L-NMMA altered this response. CONCLUSIONS: Nitric oxide seems to
      determine the absolute level of ATBF, whereas a major proportion of the
      postprandial enhancement of ATBF is under beta-adrenergic regulation in vivo in
      humans.

PMID- 14662717
TI  - Association of serum antibodies to heat-shock protein 65 with coronary
      calcification levels: suggestion of pathogen-triggered autoimmunity in early
      atherosclerosis.
AB  - BACKGROUND: Previous studies demonstrated an association between antibodies to
      mycobacterial heat-shock protein 65 (mHSP65) and carotid artery thickening. We
      examined whether mHSP65 antibodies are associated with levels of coronary
      calcification that appear to reflect preclinical coronary artery disease (CAD).
      METHODS AND RESULTS: Serum specimens from 201 healthy asymptomatic subjects (52%
      male; mean age, 56.6 years) undergoing electron-beam computed tomographic imaging
      were used to measure levels of mHSP65 and human HSP60 antibodies and antibodies
      to several infectious pathogens. We found that 84% of the study subjects had anti
      mHSP65 IgG antibodies. Mean titers of mHSP65 antibodies were higher (1:394 versus
      1:267, P=0.012) in individuals with than in those without elevated levels of
      coronary calcium (calcium score > or =150). Increasing titers of mHSP65
      antibodies were significantly associated, in a dose-response manner, with
      elevated levels of coronary calcification. Individuals with the highest titers of
      mHSP65 antibodies (> or =1:800) had an adjusted odds ratio (OR) of 14.3 for
      having elevated coronary calcium (P=0.004). Association of mHSP65 antibodies with
      elevated coronary calcification levels was independent of CAD risk factors after
      multivariate adjustment (P=0.037). Interestingly, mHSP65 antibody titers were
      correlated with Helicobacter pylori infection (P=0.004), which maintained
      significance after adjustment for CAD risk factors and seropositivities to other
      pathogens (adjusted OR, 3.1; 95% CI, 1.4 to 6.6). No association was found
      between antibodies to human HSP60 and levels of coronary calcification.
      CONCLUSIONS: Antibodies to mHSP65 are associated with elevated levels of coronary
      calcification and correlated with H pylori infection, suggesting that pathogen
      triggered autoimmunity plays a role in early atherosclerosis.

PMID- 14662718
TI  - Successful catheter ablation of electrical storm after myocardial infarction.
AB  - BACKGROUND: We report on 4 patients (aged 57 to 77 years; 3 men) who developed
      drug-refractory, repetitive ventricular tachyarrhythmias after acute myocardial
      infarction (MI). All episodes of ventricular arrhythmias were triggered by
      monomorphic ventricular premature beats (VPBs) with a right bundle-branch block
      morphology (RBBB). METHODS AND RESULTS: Left ventricular (LV) mapping was
      performed to attempt radiofrequency (RF) ablation of the triggering VPBs.
      Activation mapping of the clinical VPBs demonstrated the earliest activation in
      the anteromedial LV in 1 patient and in the inferomedial LV in 2 patients. Short,
      high-frequency, low-amplitude potentials were recorded that preceded the onset of
      each extrasystole by a maximum of 126 to 160 ms. At the same site, a Purkinje
      potential was documented that preceded the onset of the QRS complex by 23 to 26
      ms during sinus rhythm. In 1 patient, only pace mapping was attempted to identify
      areas of interest in the LV. Six to 30 RF applications abolished all local
      Purkinje potentials at the site of earliest activation and/or perfect pace
      mapping and suppressed VPBs in all patients. No episode of ventricular
      tachycardia or fibrillation has recurred for 33, 14, 6, and 5 months in patients
      1, 2, 3, and 4, respectively. CONCLUSIONS: Incessant ventricular tachyarrhythmias
      after MI may be triggered by VPBs. RF ablation of the triggering VPBs is feasible
      and can prevent drug-resistant electrical storm, even after acute MI. Catheter
      ablation of the triggering VPBs may be used as a bailout therapy in these
      patients.

PMID- 14662719
TI  - Impact of infarct-related artery flow on QT dynamicity in patients undergoing
      direct percutaneous coronary intervention for acute myocardial infarction.
AB  - BACKGROUND: Complete coronary artery reperfusion in acute myocardial infarction
      (AMI) has been shown to significantly improve survival. Electrical stability may
      be the decisive mechanism for this beneficial effect. Because electrical
      stability is largely dependent on ventricular repolarization, we sought to
      determine the impact of a modern reperfusion strategy (ie, direct percutaneous
      coronary intervention [PCI]) on QT dynamicity in AMI and examined its association
      with infarct-related artery flow. METHODS AND RESULTS: We prospectively
      investigated QT dynamicity in 128 patients undergoing direct PCI for a first AMI.
      Slopes and correlation coefficients of the linear QT/RR regression were
      determined in the time interval before reperfusion, within the initial hour after
      reperfusion, and within the remaining recording period from Holter ECG
      recordings, which were initiated on admission. Subgroup analysis based on TIMI 3
      (n=100) and TIMI 2 (n=28) flow after PCI revealed no significant differences in
      QT/RR slope before PCI (0.145+/-0.12 versus 0.160+/-0.19,P=NS). After PCI, QT/RR
      slopes increased only in the TIMI 2 subgroup (P<0.05). In TIMI 2 patients, QT/RR
      slopes were significantly steeper in the hour after PCI and in the remaining
      recording period, respectively (0.155+/-0.12 versus 0.192+/-0.15,P<0.05, and
      0.159+/-0.10 versus 0.210+/-0.17,P<0.01). CONCLUSIONS: Alterations of QT
      dynamicity in patients with incomplete reperfusion may suggest an altered
      electrical restitution, potentially providing a substrate for serious ventricular
      arrhythmias. Thus, our findings offer new insights into mechanisms by which
      complete reperfusion may affect electrical stability.

PMID- 14662720
TI  - B-type natriuretic peptide and ischemia in patients with stable coronary disease:
      data from the Heart and Soul study.
AB  - BACKGROUND: In patients with symptoms of heart failure, elevations in B-type
      natriuretic peptide (BNP) accurately identify ventricular dysfunction. However,
      BNP levels are not specific for ventricular dysfunction in patients who do not
      have overt symptoms of heart failure, suggesting that other cardiac processes
      such as myocardial ischemia may also cause elevations in BNP. METHODS AND
      RESULTS: To determine whether BNP elevations are associated with myocardial
      ischemia, we measured plasma BNP levels before performing exercise treadmill
      testing with stress echocardiography in outpatients with stable coronary disease.
      Of the 355 participants, 113 (32%) had inducible ischemia. Compared with
      participants in the lowest BNP quartile (0 to 16.4 pg/mL), those in the highest
      quartile of BNP (> or =105 pg/mL) had double the risk of inducible ischemia
      (adjusted relative risk, 2.0; 95% CI, 1.2 to 2.6; P=0.008). The relation between
      elevated BNP levels and inducible ischemia was especially evident in the 206
      participants who had a history of myocardial infarction (adjusted relative risk,
      2.6; 95% CI, 1.5 to 3.7, P=0.002) and was absent in those without a history of
      myocardial infarction (adjusted relative risk, 1.0; 95% CI, 0.3 to 2.2; P=0.9).
      This association between BNP levels and inducible ischemia remained strong after
      adjustment for measures of systolic and diastolic dysfunction. CONCLUSIONS:
      Elevated levels of BNP are independently associated with inducible ischemia among
      outpatients with stable coronary disease, particularly among those with a history
      of myocardial infarction. The observed association between BNP levels and
      ischemia may explain why tests for BNP are not specific for ventricular
      dysfunction among patients with coronary disease.

PMID- 14662721
TI  - Correlation between spontaneous electrical, calcium and mechanical activity in
      detrusor smooth muscle of the guinea-pig bladder.
AB  - 1. To investigate the cellular mechanisms underlying spontaneous excitation of
      smooth muscle of the guinea-pig urinary bladder, isometric tension was measured
      in muscle bundles while recording the membrane potential from a cell in the
      bundle with a microeletrode. Changes in the intracellular calcium concentration
      ([Ca(2+)](i); calcium transients) were recorded in strips loaded with the
      fluorescent dye, fura-PE3. 2. In 40% of preparations, individual action
      potentials and contractions, which were abolished by nifedipine (1 microm), were
      generated. In the remaining preparations, bursting action potentials and
      contractions were generated. Contractions were again abolished by nifedipine (1
      microm), while higher concentrations of nifedipine (10-30 microm) were required
      to prevent the electrical activity. 3. Carbachol (0.1 microm) increased the
      frequency of action potentials and corresponding contractions. Apamin (0.1
      microm) potentiated bursting activity and enhanced phasic contraction.
      Charybdotoxin (CTX, 50 nm) induced prolonged action potentials that generated
      enlarged contractions. In contrast, levcromakalim (0.1 microm) reduced the
      frequency of action potentials, action potential bursts and the size of the
      contractions. 4. Forskolin (0.1 microm), 8-bromoguanosin 3', 5' cyclic
      monophosphate (8Br-cGMP, 0.1 mm) and Y-26763 (10 microm) suppressed contractions
      without reducing the amplitude of either action potentials or Ca transients. 5.
      This paper confirms that action potentials and associated calcium transients are
      fundamental mechanisms in generating spontaneous contractions in smooth muscles
      of the guinea-pig bladder. However, in parallel with the excitation-contraction
      coupling, the sensitivity of the contractile proteins for Ca(2+) may play an
      important role in regulating spontaneous excitation and can be modulated by
      cyclic nucleotides and Rho kinase.

PMID- 14662722
TI  - The endothelin system in Morris hepatoma-7777: an endothelin receptor antagonist
      inhibits growth in vitro and in vivo.
AB  - 1. Plasma concentrations of endothelin are increased in patients with
      hepatocellular cancer as well as in patients with liver metastasis. However, the
      impact of these findings remains uncertain. 2. We thus analyzed the endothelin
      system in a rat hepatoma model (Morris hepatoma 7777) in vitro and in vivo. 3.
      Our study revealed that tissue concentrations of endothelin-1 (ET-1) and big-ET
      1, the precursor of ET-1, were significantly elevated in Morris hepatoma 7777 as
      compared to normal liver. The ETA receptor density was significantly elevated,
      whereas the density of the ETB receptor was decreased in Morris hepatoma 7777. 4.
      We could also demonstrate that hepatoma cells secrete ET-1. 5. Exogenously added
      ET-1 enhances hepatoma cell growth in a dose-dependent manner. Endothelin
      receptor antagonists (ETA and combined ETA/ETB receptor antagonists) inhibit
      tumor cell growth in vitro. Since the combined ETA/ETB receptor antagonist was
      more effective in vitro, we used this compound also for in vivo studies and could
      demonstrate that a combined ETA/ETB receptor antagonist is able to reduce
      hepatoma growth in vivo. 6. In conclusion, the endothelin system is activated in
      Morris hepatoma 7777 and contributes to hepatoma growth. Since endothelin
      receptor antagonists are well-tolerated upcoming clinically used drugs without
      major side effects, our data might provide a new pharmacological approach to
      reduce hepatoma growth in vivo.

PMID- 14662723
TI  - Reactive nitrogen species scavenging, rather than nitric oxide inhibition,
      protects from articular cartilage damage in rat zymosan-induced arthritis.
AB  - 1. The contribution of nitric oxide (NO) and peroxynitrite (PN) to inflammation
      in a zymosan-induced (1 mg, intra-articular, i.art.) rat model of arthritis was
      assessed by histopathology and by measuring the glycosaminoglycan (GAG) content
      of the articular cartilage. 2. Progression of the chronic synovitis in zymosan
      induced arthritis (ZYA) was associated with increased nitrite and nitrotyrosine
      (3-NT) levels in the joint exudates that paralleled a progressive loss of the GAG
      content. An increase in 3-NT was also observed after i.art. PN. 3. The
      nonselective nitric oxide synthase (NOS) inhibitor l-N(G)-nitroarginine methyl
      ester (25-75 mg x kg(-1)day(-1)) or the selective inducible NOS inhibitor
      aminoguanidine (50-100 mg x kg(-1)day(-1)) given 1 h before (prophylactic) or 3
      days after (therapeutic) injection of the zymosan ameliorated the synovitis, but
      worsened the GAG loss, as measured at the end of the experiment (day 7). 4. The
      PN scavenger uric acid (100-250 mg x kg(-1) i.p. four times daily) given
      prophylactically until the end of the experiment (day 14), in a dose compatible
      with its PN scavenging activity, significantly decreased both the synovitis and
      the GAG loss. 5. In conclusion, PN formation is associated with cartilage damage
      in addition to proinflammatory activity in ZYA. NOS inhibitors and a PN scavenger
      were able to reduce the cellular infiltration, while displaying opposite effects
      on cartilage homeostasis either by enhancing or ameliorating the damage,
      respectively.

PMID- 14662724
TI  - Desensitisation of mast cell beta2-adrenoceptor-mediated responses by salmeterol
      and formoterol.
AB  - 1. The long-acting beta(2)-adrenoceptor agonist formoterol (10(-10)-10(-6) m)
      inhibited the IgE-dependent release of histamine from human lung mast cells in a
      concentration-dependent manner. Formoterol was more potent and a full agonist
      relative to the nonselective beta-adrenoceptor agonist isoprenaline. By contrast,
      the long-acting beta(2)-adrenoceptor agonist salmeterol (10(-10)-10(-6) m) was
      about two-thirds less efficacious than either formoterol or isoprenaline as an
      inhibitor of histamine release. 2. Isoprenaline, formoterol and salmeterol (all
      at 10(-5) m) increased total cell cAMP levels in mast cells over basal by 361+/
      90 (P<0.05), 321+/-89 (P<0.05) and 64+/-24% (P>0.05), respectively. 3. Long-term
      (24 h) incubation of mast cells with formoterol (10(-6) m) or salmeterol (10(-6)
      m) essentially abolished the subsequent ability of isoprenaline to inhibit
      histamine release. Both formoterol and salmeterol were more effective at inducing
      the functional desensitisation than isoprenaline (10(-6) m) or the short-acting
      beta(2)-adrenoceptor agonist salbutamol (10(-6) m). 4. The desensitisation
      induced by long-term treatments with salmeterol and formoterol was specific for
      beta(2)-adrenoceptor-mediated inhibition of histamine release as the inhibitory
      effects of alternative cAMP-elevating compounds, prostaglandin E(2), a receptor
      mediated activator of adenylate cyclase, and forskolin, a direct activator of
      adenylate cyclase, were unaffected by desensitising treatments. 5. Radioligand
      binding studies were performed to determine beta(2)-adrenoceptor density in cell
      membranes after pretreatment (24 h) of cells with agonists. Isoprenaline,
      formoterol and salmeterol (all at 10(-6) m) reduced beta(2)-adrenoceptor density
      by 13+/-5 (P>0.05), 49+/-13 (P<0.05) and 35+/-17% (P>0.05), respectively. 6.
      These data indicate that long-term exposure of mast cells to both salmeterol and
      formoterol can cause substantial levels of desensitisation to beta(2)
      adrenoceptor-mediated responses in mast cells.

PMID- 14662725
TI  - Paradoxical early glucocorticoid induction of stem cell factor (SCF) expression
      in inflammatory conditions.
AB  - 1. Stem cell factor (SCF) is a major growth factor for mast cells, promoting
      their differentiation and chemotaxis. Its expression is regulated by
      glucocorticoids in inflammatory conditions, showing an early increased protein
      expression, before the expected anti-inflammatory decrease (Da Silva et al., Br.
      J. Pharmacol. 2002:135,1634). 2. We here evaluated the early kinetic of SCF
      expression regulated by interleukin (IL)-1beta, budesonide and the combination of
      both in human lung fibroblasts in culture. 3. Budesonide potentiated the IL-1beta
      enhanced expression of SCF mRNA (+103%) and protein (+98%) very shortly after
      treatment (at 30 min and 1 h, respectively). A gentle downregulation followed.
      This potentiating effect of budesonide was related to increased SCF mRNA
      stability and SCF gene transcription. 4. Deletion of a kappaB-like site that we
      identified in the first intron of the SCF gene, in a luciferase reporter system,
      abolished the potentiation by budesonide, as well as the effect of IL-1beta
      alone, as compared to the wild-type construction activity. 5. All budesonide
      induced effects were glucocorticoid-receptor dependent, since they were
      reproduced by dexamethasone and blocked by RU486. 6. IL-1beta+budesonide did not
      affect the relative expression of the soluble and membrane-bound forms of SCF. 7.
      In conclusion, our results clearly show that glucocorticoids act very early to
      adversely increase the expression of SCF mRNA and protein in the inflammatory
      conditions created by IL-1beta, and that this effect involves increased mRNA
      stability and increased gene expression through activation of the NF-kappaB-like
      responsive element.

PMID- 14662726
TI  - A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates
      neuropathic pain-like behavior after spinal cord and peripheral nerve injury.
AB  - 1. Nitric oxide (NO) participates, at least in part, to the establishment and
      maintenance of pain after nerve injury. Therefore, drugs that target the NO/cGMP
      signaling pathway are of interest for the treatment of human neuropathic pain.
      Various compounds endowed with NO-releasing properties modulate the expression
      and function of inducible nitric oxide synthase (iNOS), the key enzyme
      responsible for sustained NO production under pathological conditions including
      neuropathic pain. 2. With this background, we synthesized a new chemical entity,
      [1-(aminomethyl)cyclohexane acetic acid 3-(nitroxymethyl)phenyl ester] NCX8001,
      which has a NO-releasing moiety bound to gabapentin, a drug currently used for
      the clinical management of neuropathic pain. We examined the pharmacological
      profile of this drug with respect to its NO-releasing properties in vitro as well
      as to its efficacy in treating neuropathic pain conditions (allodynia) consequent
      to experimental sciatic nerve or spinal cord injuries. 3. NCX8001 (1-30 microm)
      released physiologically relevant concentrations of NO as it induced a
      concentration-dependent activation of soluble guanylyl cyclase (EC(50)=5.6
      microm) and produced consistent vasorelaxant effects in noradrenaline
      precontracted rabbit aortic rings (IC(50)=1.4 microm). 4. NCX8001, but not
      gabapentin, counteracted in a concentration-dependent fashion lipopolysaccharide
      induced overexpression and function of iNOS in RAW264.7 macrophages cell line.
      Furthermore, NCX8001 also inhibited the release of tumor necrosis factor alpha
      (TNFalpha) from stimulated RAW264.7 cells. 5. NCX8001 (28-280 micromol x kg(-1),
      i.p.) reduced the allodynic responses of spinal cord injured rats in a dose
      dependent fashion while lacking sedative or motor effects. In contrast,
      gabapentin (170-580 micromol x kg(-1), i.p.) resulted less effective and elicited
      marked side effects. 6. NCX8001 alleviated the allodynia-like responses of rats
      to innocuous mechanical or cold stimulation following lesion of the sciatic
      nerve. This effect was not shared by equimolar doses of gabapentin. 7.
      Potentially due to the slow releasing kinetics of NO, NCX8001 alleviated pain
      like behaviors in two rat models of neuropathic pain in a fashion that is
      superior to its parent counterpart gabapentin. This new gabapentin derivative,
      whose mechanism deserves to be explored further, offers new hopes to the
      treatment of human neuropathic pain.

PMID- 14662727
TI  - G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not
      opioid withdrawal.
AB  - 1. Tolerance to opioids frequently follows repeated drug administration and
      affects the clinical utility of these analgesics. Studies in simple cellular
      systems have demonstrated that prolonged activation of opioid receptors produces
      homologous receptor desensitization by G-protein receptor kinase mediated
      receptor phosphorylation and subsequent beta-arrestin binding. To define the role
      of this regulatory mechanism in the control of the electrophysiological and
      behavioral responses to opioids, we used mice having a targeted disruption of the
      G-protein receptor kinase 3 (GRK3) gene. 2. Mice lacking GRK3 did not differ from
      wild-type littermates neither in their response latencies to noxious stimuli on
      the hot-plate test nor in their acute antinociceptive responses to fentanyl or
      morphine. 3. Tolerance to the electrophysiological response to the opioid
      fentanyl, measured in vitro in the hippocampus, was blocked by GRK3 deletion. In
      addition, tolerance to the antinociceptive effects of fentanyl was significantly
      reduced in GRK3 knockouts compared to wild-type littermate controls. 4. Tolerance
      to the antinociceptive effects of morphine was not affected by GRK3 deletion
      although morphine tolerance in hippocampal slices from GRK3 knockout mice was
      significantly inhibited. Tolerance developed more slowly in vitro to morphine
      than fentanyl supporting previous work in in vitro systems showing a correlation
      between agonist efficacy and GRK3-mediated desensitization. 5. The results of
      these studies suggest that GRK3-mediated mechanisms are important components of
      both electrophysiologic and behavioral opioid tolerance. Fentanyl, a high
      efficacy opioid, more effectively produced GRK3-dependent effects than morphine,
      a low efficacy agonist.

PMID- 14662728
TI  - An improved model for the binding of lidocaine and structurally related local
      anaesthetics to fast-inactivated voltage-operated sodium channels, showing
      evidence of cooperativity.
AB  - 1. The interaction of lidocaine-like local anaesthetics with voltage-operated
      sodium channels is traditionally assumed to be characterized by tighter binding
      of the drugs to depolarized channels. As inactivated and drug-bound channels are
      both unavailable on depolarization, an indirect approach is required to yield
      estimates for the dissociation constants from channels in inactivated states. The
      established model, originally described by Bean et al., describes the difference
      in affinity between resting and inactivated states in terms of the concentration
      dependence of the voltage shift in the availability curve. We have tested the
      hypothesis that this model, which assumes a simple Langmuir relationship, could
      be improved by introducing a Hill-type exponent, which would take into account
      potential sources of cooperativity. 2. Steady-state block by lidocaine was
      studied in heterologously (HEK 293) expressed human skeletal muscle sodium
      channels and compared with experimental data previously obtained for 2,6
      dimethylphenol, 3,5-dimethyl-4-chlorophenol, and 4-chlorophenol. Cells were
      clamped to membrane potentials from -150 to -5 mV, and a subsequent test pulse
      was used to assess the number of channels available to open. 3. All compounds
      shifted the voltage dependence of channel availability in the direction of
      negative prepulse potentials. Prediction of the concentration dependence of the
      voltage shift in the availability curve was improved by the modified model, as
      shown by a marked reduction in the residual sum of squares. 4. For all compounds,
      the Hill-type exponent was significantly greater than one. These results could be
      interpreted in the light of the contemporary hypothesis that lidocaine functions
      as an allosteric gating effector to enhance sodium channel inactivation by
      strengthening the latch mechanism of inactivation, which is considered to be a
      particle-binding process allosterically coupled to activation. Alternatively,
      they could be interpreted by postulating additional binding sites for lidocaine
      on fast-inactivated sodium channels.

PMID- 14662729
TI  - Changes in rectal temperature and ECoG spectral power of sensorimotor cortex
      elicited in conscious rabbits by i.c.v. injection of GABA, GABA(A) and GABA(B)
      agonists and antagonists.
AB  - 1. In order to ascertain whether both GABA(A) and GABA(B), or only GABA(B)
      receptors, directly modulate thermoregulation in conscious rabbits,
      GABA(A)/GABA(B) agonist and antagonist agents were injected
      intracerebroventricularly in conscious rabbits while monitoring changes in rectal
      temperature (RT), gross motor behaviour (GMB) and electrocorticogram (ECoG) power
      spectra (ps) from sensorimotor cortices. 2. GABA (48 micromol), nipecotic acid
      (50 nmol), THIP (60 nmol), muscimol (18 nmol) and baclofen (8 nmol) induced
      hypothermia (-deltaRTmax values of 1.70+/-0.1, 1.4+/-0.2, 1.0+/-0.4, 1.1+/-0.2
      and 1.6+/-0.3 degrees C, respectively), accompanied by inhibition of GMB and ECoG
      synchronization. THIP increased ps at delta frequency band (1.1-3.3 Hz), while
      GABA, nipecotic acid, muscimol and baclofen did the same at both delta and (4.6
      6.5 Hz) frequency bands. ECoG ps changes were concomitant or even preceded
      hypothermia. 3. Bicuculline (1.8 nmol) induced hyperthermia (deltaRTmax 1.2+/-0.5
      degrees C) and slight excitation of GMB, while CGP35348 (1.2 micromol) did not
      affect RT nor GMB. Both compounds did not affect ECoG ps. 4. Bicuculline
      potentiated muscimol-induced hypothermia, inhibition of GMB and synchronization
      of ECoG, while CGP35348 fully antagonized these effects. 5. In conclusion, the
      present results, while confirming the prevailing role of GABA(B), also outline a
      direct involvement of GABA(A) receptors in the central mechanisms of
      thermoregulation. Ascending inhibition towards discrete cortical areas
      controlling muscular activity and thermogenesis may result from GABA receptor
      activation in neurones proximal to the ventricles, thus contributing to
      hypothermia, although hypothermia-induced reduction of neuronal activity of these
      cortical areas cannot be ruled out.

PMID- 14662730
TI  - A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide
      receptor-like 1 receptor.
AB  - 1. Human formyl peptide-receptor-like-1 (FPRL-1) is a promiscuous G protein
      coupled receptor (GPCR), and belongs to a chemoattractant receptor family
      protein. This receptor has been reported to interact with various host-derived
      peptides and lipids involved in inflammatory responses. We described here, a
      novel role for FPRL-1 as a high-affinity beta-chemokine receptor for an N
      terminally truncated form of the CKbeta8 (CCL23/MPIF-1) splice variant CKbeta8-1
      (22-137 aa). 2. RT-PCR analysis of mRNA derived from human tissues and cells
      revealed a predominant expression of FPRL-1 in inflammatory cells, particularly
      in neutrophils. 3. Intracellular calcium mobilisation assay, used as screening
      tool, in recombinant Chinese hamster ovary (CHO-K1) and human embryonic kidney
      (HEK293s) cells coexpressing FPRL-1 and Galpha(16), demonstrated FPRL-1 is a
      functional high-affinity receptor for CKbeta8-1 (46-137 aa, sCKbeta8-1), with
      pEC(50) values of 9.13 and 8.85, respectively. 4. The FPRL-1 activation in CHO-K1
      cells is mediated by Galpha(i)/Galpha(o) proteins, as assessed by pertussis toxin
      sensitivity and inhibition of forskolin-induced cyclic AMP accumulation. 5.
      Binding experiments were performed with a radio-iodinated synthetic peptide,
      [(125-)I]-WKYMVm, a known potent FPRL-1 agonist. CHO-K1 cell membranes expressing
      FPRL-1 bound [(125-)I]-WKYMVm with a K(d) value of 9.34. Many known FPRL-1
      agonists were tested and sCKbeta8-1 was the most effective nonsynthetic ligand in
      displacing the radiolabelled agonist, with a pIC(50) of 7.97. 6. The functional
      significance of sCKbeta8-1 interaction with FPRL-1 was further demonstrated by
      the activation of polymorphonuclear leukocytes (PMNs) calcium mobilisation and
      chemotaxis. These interactions were shown to be via FPRL-1 by specific blockade
      of PMNs activation in the presence of an FPRL-1 antibody.

PMID- 14662731
TI  - Adenine nucleotides inhibit recombinant N-type calcium channels via G protein
      coupled mechanisms in HEK 293 cells; involvement of the P2Y13 receptor-type.
AB  - 1. N-type Ca(2+) channel modulation by an endogenous P2Y receptor was
      investigated by the whole-cell patch-clamp method in HEK 293 cells transfected
      with the functional rabbit N-type calcium channel. 2. The current responses
      (I(Ca(N))) to depolarizing voltage steps were depressed by ATP in a concentration
      dependent manner. Inclusion of either guanosine 5'-O-(3-thiodiphosphate) or
      pertussis toxin into the pipette solution as well as a strongly depolarizing
      prepulse abolished the inhibitory action of ATP. 3. In order to identify the P2Y
      receptor subtype responsible for this effect, several preferential agonists and
      antagonists were studied. Whereas the concentration-response curves of ADP and
      adenosine 5'-O-(2-thiodiphosphate) indicated a higher potency of these agonists
      than that of ATP, alpha,beta-methylene ATP, UTP and UDP were considerably less
      active. The effect of ATP was abolished by the P2Y receptor antagonists suramin
      and N(6)-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma
      dichloromethylene-ATP, but not by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic
      acid, 2'deoxy-N(6)-methyladenosine-3',5'-diphosphate or 2-methylthio AMP. 4.
      Using reverse transcription and polymerase chain reaction, mRNA for the P2Y(1),
      P2Y(4), P2Y(6), P2Y(11) and P2Y(13) receptor subtypes, but not the P2Y(2), and
      P2Y(12) subtypes, was detected in HEK 293 cells. 5. Immunocytochemistry confirmed
      the presence of P2Y(1), and to a minor extent that of P2Y(4), but not of P2Y(2)
      receptors. 6. Hence, it is tempting to speculate that P2Y(13) receptors may
      inhibit N-type Ca(2+) channels via the betagamma subunits of the activated G(i)
      protein.

PMID- 14662732
TI  - Repeated treatment with the synthetic cannabinoid WIN 55,212-2 reduces both
      hyperalgesia and production of pronociceptive mediators in a rat model of
      neuropathic pain.
AB  - The antinociceptive properties of cannabinoids in persistent pain are not fully
      elucidated. We investigated the effect of repeated treatment with the synthetic
      cannabinoid receptor agonist WIN 55,212-2 on the neuropathic pain induced in rats
      by chronic constriction of the sciatic nerve. WIN 55,212-2 administered daily
      throughout the development of neuropathy reversed the hyperalgesia, at a dose
      (0.1 mg x kg(-1), s.c.) that had no effect on the nociceptive responses of either
      paw contralateral to the sciatic ligation or of animals subjected to sham
      surgery. At 14 days after injury, the levels of mediators known to be involved in
      neuropathic pain, such as prostaglandin E2, NO and the neuronal NOS, were
      increased. Repeated treatment with WIN 55,212-2 abolished these increases. In the
      light of the current clinical need for neuropathic pain treatments, these
      findings indicate that cannabinoid agonists, at doses devoid of psychoactive
      effects, could constitute important compounds for the development of new
      analgesics.

PMID- 14662733
TI  - Ligands of the peroxisome proliferator-activated receptor-gamma and heart
      failure.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors that are
      related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily
      comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. There is good
      evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce
      myocardial tissue injury and infarct size. The use of PPAR-gamma agonists in the
      treatment of heart failure is, however, controversial.

PMID- 14662734
TI  - Peroxisome proliferator activated-receptor agonism and left ventricular
      remodeling in mice with chronic myocardial infarction.
AB  - 1. Peroxisome proliferator activated receptor gamma (PPARgamma) has been
      implicated in several cellular pathways assumed to beneficially affect heart
      failure progression. In contrast, population-based studies demonstrate an
      increased incidence of heart failure in patients treated with PPARgamma agonists.
      Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on
      chronic left ventricular remodeling after experimental myocardial infarction (MI)
      in mice. 2. Mice were treated with placebo or pioglitazone (20 mg x kg(-1) by
      gavage) from week 1 to week 6 after ligation of the left anterior descending
      artery. Serial transthoracic echocardiography was performed at weeks 1, 3, and 6.
      3. Over 6 weeks, there was no difference in mortality (placebo 12%, pioglitazone
      10%). Echocardiography showed significant left ventricular dilatation in animals
      with MI (week 6, end-systolic area, placebo sham 9.6+/-1.3 vs placebo MI 14.4+/
      2.5 mm(2)). However, there was no difference between the placebo and pioglitazone
      groups (week 6, end-systolic area, pioglitazone MI 14.8+/-2.9 mm(2), P=NS vs
      placebo). 4. Moreover, there were no changes in metabolic parameters,
      inflammation, and collagen deposition. Endothelial function in the aorta was not
      changed by PPARgamma activation. 5. In conclusion, PPARgamma activation did not
      adversely affect left ventricular remodeling and survival in mice with chronic
      MI. However, we were also not able to identify a protective effect of
      pioglitazone.

PMID- 14662736
TI  - Evidence in locomotion test for the functional heterogeneity of ORL-1 receptors.
AB  - 1. The ORL1 agonists nociceptin and Ro 64-6198 were compared in their ability to
      modify spontaneous locomotor activity in male NMRI mice not habituated to the
      test environment. 2. Higher doses of nociceptin (>5 nmol i.c.v.) reduced whereas
      lower doses (<1 nmol i.c.v.) stimulated locomotor activity. Both effects were
      blocked by the putative ORL1 antagonists [NPhe1]nociceptin(1-13)NH2 (10 nmol
      i.c.v.) and UFP101 (10 nmol, i.c.v.). The effects were also blocked by naloxone
      benzoylhydrazone (1 mg x kg(-1) s.c.), but not by the nonselective opioid
      antagonist naloxone (1 mg x kg(-1) s.c.). 3 In contrast to nociceptin, the
      synthetic ORL1 agonist Ro 64-6198 (0.01-1.0 mg x kg(-1) i.p.) produced monophasic
      inhibition of locomotor activity, which was insensitive to the treatment with
      [NPhe1]nociceptin(1-13)NH2 or naloxone benzoylhydrazone. Treatment with UFP101
      abolished the locomotor inhibition induced by Ro 64-6198 (1.0 mg x kg(-1)),
      whereas naloxone (1.0 mg x kg(-1), s.c.) further increased the locomotor
      inhibitory effects. 4. Naloxone benzoylhydrazone (0.3; 1.0 and 3.0 mg x kg(-1)
      s.c.) increased locomotor activity, although the effect was statistically
      significant only with the highest dose used. 5. Pretreatment with the tyrosine
      hydroxylase inhibitor H44-68 totally eliminated the motor-stimulatory effects of
      low doses of nociceptin, probably via dopamine depletion. 6. The results suggest
      that nociceptin stimulates locomotor activity at low doses if dopamine activity
      is intact. High doses of nociceptin and all the tested doses of Ro 64-6198 seem
      to interact with a functionally different subset of ORL1 receptors. In addition,
      the effects of Ro 64-6198 are modulated by tonic opioid receptor activity.

PMID- 14662735
TI  - Phospholipase C, but not InsP3 or DAG, -dependent activation of the muscarinic
      receptor-operated cation current in guinea-pig ileal smooth muscle cells.
AB  - 1. In visceral smooth muscles, both M(2) and M(3) muscarinic receptor subtypes
      are found, and produce two major metabolic effects: adenylyl cyclase inhibition
      and PLCbeta activation. Thus, we studied their relevance for muscarinic cationic
      current (mI(CAT)) generation, which underlies cholinergic excitation. Experiments
      were performed on single guinea-pig ileal cells using patch-clamp recording
      techniques under conditions of weakly buffered [Ca(2+)](i) (either using 50
      microm EGTA or 50-100 microm fluo-3 for confocal fluorescence imaging) or with
      [Ca(2+)](i) 'clamped' at 100 nm using 10 mm BAPTA/CaCl(2) mixture. 2. Using a
      cAMP-elevating agent (1 microm isoproterenol) or a membrane-permeable cAMP analog
      (10 microm 8-Br-cAMP), we found no evidence for mI(CAT) modulation through a
      cAMP/PKA pathway. 3. With low [Ca(2+)](i) buffering, the PLC blocker U-73122 at
      2.5 microm almost abolished mI(CAT), in some cases without any significant effect
      on [Ca(2+)](i). When [Ca(2+)](i) was buffered at 100 nm, U-73122 reduced both
      carbachol- and GTPgammaS-induced mI(CAT) maximal conductances (IC(50)=0.5-0.6
      microm) and shifted their activation curves positively. 4. U-73343, a weak PLC
      blocker, had no effect on GTPgammaS-induced mI(CAT), but weakly inhibited
      carbachol-induced current, possibly by competitively inhibiting muscarinic
      receptors, since the inhibition could be prevented by increasing the carbachol
      concentration to 1 mm. Aristolochic acid and D-609, which inhibit PLA(2) and
      phosphatidylcholine-specific PLC, respectively, had no or very small effects on
      mI(CAT), suggesting that these enzymes were not involved. 5. InsP(3) (1 microm)
      in the pipette or OAG (20 microm) applied externally had no effect on mI(CAT) or
      its inhibition by U-73122. Ca(2+) store depletion (evoked by InsP(3), or by
      combined cyclopiazonic acid, ryanodine and caffeine treatment) did not induce any
      significant current, and had no effect on mI(CAT) in response to carbachol when
      [Ca(2+)](i) was strongly buffered to 100 nm. 6. It is concluded that
      phosphatidylinositol-specific PLC modulates mI(CAT) via Ca(2+) release, but also
      does so independently of InsP(3), DAG, Ca(2+) store depletion or a rise of
      [Ca(2+)](i). Our present results explain the previously established 'permissive'
      role of the M(3) receptor subtype in mI(CAT) generation, and provide a new
      insight into the molecular mechanisms underlying the shifts of the cationic
      conductance activation curve.

PMID- 14662737
TI  - Heterogeneity of neuronal and smooth muscle receptors involved in the VIP- and
      PACAP-induced relaxations of the pig intravesical ureter.
AB  - 1. The mechanisms and receptors involved in the vasoactive intestinal peptide
      (VIP)- and pituitary adenylate cyclase-activating polypeptide (PACAP)-induced
      relaxations of the pig intravesical ureter were investigated. 2. VIP, PACAP 38
      and PACAP 27 concentration-dependently relaxed U46619-contracted ureteral strips
      with a similar potency. [Ala(11,22,28)]-VIP, a VPAC(1) agonist, showed
      inconsistent relaxations. 3. The neuronal voltage-gated Ca(2+) channel inhibitor,
      omega-conotoxin GVIA (omega-CgTX, 1 microm), reduced the VIP relaxations.
      Urothelium removal or blockade of capsaicin-sensitive primary afferents, nitric
      oxide (NO) synthase and guanylate cyclase with capsaicin (10 microm), N(G)-nitro
      l-arginine (l-NOARG, 100 microm) and 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ, 5 microm), respectively, did not change the VIP relaxations. However, the
      PACAP 38 relaxations were reduced by omega-CgTX, capsaicin, l-NOARG and ODQ. 4.
      The VIP and VIP/PACAP receptor antagonists, [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]
      VIP (1 microm) and PACAP (6-38) (0.4 microm), inhibited VIP and VIP and PACAP 38,
      respectively, relaxations. 5. The nonselective and large-conductance Ca(2)
      activated K(+) channel blockers, tetraethylammonium (3 mm) and charybdotoxin (0.1
      microm), respectively, and neuropeptide Y (0.1 microm) did not modify the VIP
      relaxations. The small-conductance Ca(2)-activated K(+) channel blocker apamin (1
      microm) did not change the PACAP 27 relaxations. 6. The cAMP-dependent protein
      kinase A (PKA) blocker, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic
      monophosphorothioate (Rp-8-CPT-cAMPS, 100 microm), reduced VIP relaxations. The
      phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator
      forskolin relaxed ureteral preparations. The rolipram relaxations were reduced by
      Rp-8-CPT-cAMPS. Forskolin (30 nm) evoked a potentiation of VIP relaxations. 7.
      These results suggest that VIP and PACAP relax the pig ureter through smooth
      muscle receptors, probably of the VPAC(2) subtype, linked to a cAMP-PKA pathway.
      Neuronal VPAC receptors localized at motor nerves and PAC(1) receptors placed at
      sensory nerves and coupled to NO release, seem also to be involved in the VIP and
      PACAP 38 relaxations.

PMID- 14662738
TI  - Haemodynamic effects of the selective phosphodiesterase 5 inhibitor, UK-357,903,
      in conscious SHR.
AB  - 1. Regional haemodynamic responses to a continuous, 4-day infusion of the
      selective phosphodiesterase type 5 inhibitor, UK-357,903 (0.133 or 1.33 mg x kg(
      1) h(-1)) were measured in conscious spontaneously hypertensive rats, and
      compared with those of enalapril (1 mg x kg(-1) h(-1)). 2. Both doses of UK
      357,903 caused modest reductions in mean blood pressure that were not dose
      dependent and only significantly different from the vehicle effects on Day 1 of
      the study (mean -11.8 and -15.3 mmHg for low and high doses, respectively). UK
      357,903 had mesenteric and hindquarters vasodilator effects, which were, again,
      similar for both dose levels and only significantly different from vehicle on Day
      1. Neither dose of UK-357,903 affected renal vascular conductance or heart rate.
      3. Although the haemodynamic effects of UK-357,903 were not clearly dose-related
      and some appeared to wane with time, geometric mean plasma levels of UK-357,903
      increased in proportion to dose, and were sustained throughout the infusion
      period. Furthermore, plasma cyclic guanosine monophosphate, a biomarker of
      phosphodiesterase 5 inhibition, was persistently elevated, and increased with
      increasing dose. 4. Enalapril caused a fall in mean blood pressure on day 1 (
      14.1 mmHg) that was associated with dilatation in renal, mesenteric and
      hindquarters vascular beds. The haemodynamic effects of enalapril were sustained
      or increased over the 4-day infusion, although plasma free drug levels were
      stable. 5. In conclusion, we have shown regional and temporal changes in the
      haemodynamic effects of UK-357,903, which may be due to activation of
      compensatory mechanisms, but there were no signs of functional compensation to
      the cardiovascular effects of enalapril.

PMID- 14662739
TI  - IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrients.
AB  - Insulin-like growth factors (IGFs) are essential for skeletal muscle development,
      regeneration, and hypertrophy. Although autocrine actions of IGF-II are known to
      initiate myoblast differentiation, the regulatory elements and upstream signaling
      pathways for myogenic expression of IGF-II remain elusive. Here, we report the
      regulation of IGF-II transcription by mTOR, as well as by amino acid sufficiency,
      through the IGF-II promoter 3 and a downstream enhancer during C2C12 myoblast
      differentiation. Furthermore, we present evidence that IGF production, and not
      IGF signaling, is the primary target for mTOR's function in the initiation of
      differentiation. Moreover, myogenic signaling by mTOR is independent of its
      kinase activity and mediated by the PI3K-Akt pathway. Our findings represent the
      first identification of a signaling pathway that regulates IGF-II expression in
      myogenesis and implicate the mTOR-IGF axis as a molecular link between
      nutritional levels and skeletal muscle development.

PMID- 14662740
TI  - Meiotic condensin is required for proper chromosome compaction, SC assembly, and
      resolution of recombination-dependent chromosome linkages.
AB  - Condensin is an evolutionarily conserved protein complex that helps mediate
      chromosome condensation and segregation in mitotic cells. Here, we show that
      condensin has two activities that contribute to meiotic chromosome condensation
      in Saccharomyces cerevisiae. One activity, common to mitosis, helps mediate axial
      length compaction. A second activity promotes chromosome individualization with
      the help of Red1 and Hop1, two meiotic specific components of axial elements.
      Like Red1 and Hop1, condensin is also required for efficient homologue pairing
      and proper processing of double strand breaks. Consistent with these functional
      links condensin is necessary for proper chromosomal localization of Red1 and Hop1
      and the subsequent assembly of the synaptonemal complex. Finally, condensin has a
      Red1/Hop1-independent role in the resolution of recombination-dependent linkages
      between homologues in meiosis I. The existence of distinct meiotic activities of
      condensin (axial compaction, individualization, and resolution of recombination
      dependent links) provides an important framework to understand condensin's role
      in both meiotic and mitotic chromosome structure and function.

PMID- 14662741
TI  - Chromosome instability in colorectal tumor cells is associated with defects in
      microtubule plus-end attachments caused by a dominant mutation in APC.
AB  - The attachment of microtubule plus ends to kinetochores and to the cell cortex is
      essential for the fidelity of chromosome segregation. Here, we characterize the
      causes underlying the high rates of chromosome instability (CIN+) observed in
      colorectal tumor cells. We show that CIN+ tumor cells exhibit inefficient
      microtubule plus-end attachments during mitosis, accompanied by impairment of
      chromosome alignment in metaphase. The mitotic abnormalities associated with CIN+
      tumor cells correlated with status of adenomatous polyposis coli (APC).
      Importantly, we have shown that a single truncating mutation in APC, similar to
      mutations found in tumor cells, acts dominantly to interfere with microtubule
      plus-end attachments and to cause a dramatic increase in mitotic abnormalities.
      We propose that APC functions to modulate microtubule plus-end attachments during
      mitosis, and that a single mutant APC allele predisposes cells to increased
      mitotic abnormalities, which may contribute to tumor progression.

PMID- 14662742
TI  - Regulation of KinI kinesin ATPase activity by binding to the microtubule lattice.
AB  - KinI kinesins are important in regulating the complex dynamics of the microtubule
      cytoskeleton. They are unusual in that they depolymerize, rather than move along
      microtubules. To determine the attributes of KinIs that distinguish them from
      translocating kinesins, we examined the ATPase activity, microtubule affinity,
      and three-dimensional microtubule-bound structure of a minimal KinI motor domain.
      Together, the kinetic, affinity, and structural data lead to the conclusion that
      on binding to the microtubule lattice, KinIs release ADP and enter a stable, low
      affinity, regulated state, from which they do not readily progress through the
      ATPase cycle. This state may favor detachment, or diffusion of the KinI to its
      site of action, the microtubule ends. Unlike conventional translocating kinesins,
      which are microtubule lattice-stimulated ATPases, it seems that with KinIs,
      nucleotide-mediated modulation of tubulin affinity is only possible when it is
      coupled to protofilament deformation. This provides an elegant mechanistic basis
      for their unique depolymerizing activity.

PMID- 14662743
TI  - Yeast homotypic vacuole fusion requires the Ccz1-Mon1 complex during the
      tethering/docking stage.
AB  - The function of the yeast lysosome/vacuole is critically linked with the
      morphology of the organelle. Accordingly, highly regulated processes control
      vacuolar fission and fusion events. Analysis of homotypic vacuole fusion
      demonstrated that vacuoles from strains defective in the CCZ1 and MON1 genes
      could not fuse. Morphological evidence suggested that these mutant vacuoles could
      not proceed to the tethering/docking stage. Ccz1 and Mon1 form a stable protein
      complex that binds the vacuole membrane. In the absence of the Ccz1-Mon1 complex,
      the integrity of vacuole SNARE pairing and the unpaired SNARE class C Vps/HOPS
      complex interaction were both impaired. The Ccz1-Mon1 complex colocalized with
      other fusion components on the vacuole as part of the cis-SNARE complex, and the
      association of the Ccz1-Mon1 complex with the vacuole appeared to be regulated by
      the class C Vps/HOPS complex proteins. Accordingly, we propose that the Ccz1-Mon1
      complex is critical for the Ypt7-dependent tethering/docking stage leading to the
      formation of a trans-SNARE complex and subsequent vacuole fusion.

PMID- 14662744
TI  - SHP-1 negatively regulates neuronal survival by functioning as a TrkA
      phosphatase.
AB  - Nerve growth factor (NGF) mediates the survival and differentiation of neurons by
      stimulating the tyrosine kinase activity of the TrkA/NGF receptor. Here, we
      identify SHP-1 as a phosphotyrosine phosphatase that negatively regulates TrkA.
      SHP-1 formed complexes with TrkA at Y490, and dephosphorylated it at Y674/675.
      Expression of SHP-1 in sympathetic neurons induced apoptosis and TrkA
      dephosphorylation. Conversely, inhibition of endogenous SHP-1 with a dominant
      inhibitory mutant stimulated basal tyrosine phosphorylation of TrkA, thereby
      promoting NGF-independent survival and causing sustained and elevated TrkA
      activation in the presence of NGF. Mice lacking SHP-1 had increased numbers of
      sympathetic neurons during the period of naturally occurring neuronal cell death,
      and when cultured, these neurons survived better than wild-type neurons in the
      absence of NGF. These data indicate that SHP-1 can function as a TrkA
      phosphatase, controlling both the basal and NGF-regulated level of TrkA activity
      in neurons, and suggest that SHP-1 regulates neuron number during the
      developmental cell death period by directly regulating TrkA activity.

PMID- 14662745
TI  - NF-M is an essential target for the myelin-directed "outside-in" signaling
      cascade that mediates radial axonal growth.
AB  - Neurofilaments are essential for acquisition of normal axonal calibers. Several
      lines of evidence have suggested that neurofilament-dependent structuring of
      axoplasm arises through an "outside-in" signaling cascade originating from
      myelinating cells. Implicated as targets in this cascade are the highly
      phosphorylated KSP domains of neurofilament subunits NF-H and NF-M. These are
      nearly stoichiometrically phosphorylated in myelinated internodes where radial
      axonal growth takes place, but not in the smaller, unmyelinated nodes. Gene
      replacement has now been used to produce mice expressing normal levels of the
      three neurofilament subunits, but which are deleted in the known phosphorylation
      sites within either NF-M or within both NF-M and NF-H. This has revealed that the
      tail domain of NF-M, with seven KSP motifs, is an essential target for the
      myelination-dependent outside-in signaling cascade that determines axonal caliber
      and conduction velocity of motor axons.

PMID- 14662746
TI  - The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is
      essential for the radial growth and cytoskeletal architecture of axons but not
      for regulating neurofilament transport rate.
AB  - The phosphorylated carboxyl-terminal "tail" domains of the neurofilament (NF)
      subunits, NF heavy (NF-H) and NF medium (NF-M) subunits, have been proposed to
      regulate axon radial growth, neurofilament spacing, and neurofilament transport
      rate, but direct in vivo evidence is lacking. Because deletion of the tail domain
      of NF-H did not alter these axonal properties (Rao, M.V., M.L. Garcia, Y.
      Miyazaki, T. Gotow, A. Yuan, S. Mattina, C.M. Ward, N.S. Calcutt, Y. Uchiyama,
      R.A. Nixon, and D.W. Cleveland. 2002. J. Cell Biol. 158:681-693), we investigated
      possible functions of the NF-M tail domain by constructing NF-M tail-deleted (NF
      MtailDelta) mutant mice using an embryonic stem cell-mediated "gene knockin"
      approach that preserves normal ratios of the three neurofilament subunits. Mutant
      NF-MtailDelta mice exhibited severely inhibited radial growth of both motor and
      sensory axons. Caliber reduction was accompanied by reduced spacing between
      neurofilaments and loss of long cross-bridges with no change in neurofilament
      protein content. These observations define distinctive functions of the NF-M tail
      in regulating axon caliber by modulating the organization of the neurofilament
      network within axons. Surprisingly, the average rate of axonal transport of
      neurofilaments was unaltered despite these substantial effects on axon
      morphology. These results demonstrate that NF-M tail-mediated interactions of
      neurofilaments, independent of NF transport rate, are critical determinants of
      the size and cytoskeletal architecture of axons, and are mediated, in part, by
      the highly phosphorylated tail domain of NF-M.

PMID- 14662747
TI  - Small GTPase Rin induces neurite outgrowth through Rac/Cdc42 and calmodulin in
      PC12 cells.
AB  - The novel Ras-like small GTPase Rin is expressed prominently in adult neurons,
      and binds calmodulin (CaM) through its COOH-terminal-binding motif. It might be
      involved in calcium/CaM-mediated neuronal signaling, but Rin-mediated signal
      transduction pathways have not yet been elucidated. Here, we show that expression
      of Rin induces neurite outgrowth without nerve growth factor or mitogen-activated
      protein kinase activation in rat pheochromocytoma PC12 cells. Rin-induced neurite
      outgrowth was markedly inhibited by coexpression with dominant negative Rac/Cdc42
      protein or CaM inhibitor treatment. We also found that expression of Rin elevated
      the endogenous Rac/Cdc42 activity. Rin mutant proteins, in which the mutation
      disrupted association with CaM, failed to induce neurite outgrowth irrespective
      of Rac/Cdc42 activation. Disruption of endogenous Rin function inhibited the
      neurite outgrowth stimulated by forskolin and extracellular calcium entry through
      voltage-dependent calcium channel evoked by KCl. These findings suggest that Rin
      mediated neurite outgrowth signaling requires not only endogenous Rac/Cdc42
      activation but also Rin-CaM association, and that endogenous Rin is involved in
      calcium/CaM-mediated neuronal signaling pathways.

PMID- 14662748
TI  - Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic
      diabetes insipidus.
AB  - Vasopressin regulates body water conservation by redistributing aquaporin-2
      (AQP2) water channels from intracellular vesicles to the apical surface of renal
      collecting ducts, resulting in water reabsorption from urine. Mutations in AQP2
      cause autosomal nephrogenic diabetes insipidus (NDI), a disease characterized by
      the inability to concentrate urine. Here, we report a frame-shift mutation in
      AQP2 causing dominant NDI. This AQP2 mutant is a functional water channel when
      expressed in Xenopus oocytes. However, expressed in polarized renal cells, it is
      misrouted to the basolateral instead of apical plasma membrane. Additionally,
      this mutant forms heterotetramers with wild-type AQP2 and redirects this complex
      to the basolateral surface. The frame shift induces a change in the COOH terminus
      of AQP2, creating both a leucine- and a tyrosine-based motif, which cause the
      reversed sorting of AQP2. Our data reveal a novel cellular phenotype in dominant
      NDI and show that dominance of basolateral sorting motifs in a mutant subunit can
      be the molecular basis for disease.

PMID- 14662749
TI  - ARF6 controls post-endocytic recycling through its downstream exocyst complex
      effector.
AB  - The small guanosine triphosphate (GTP)-binding protein ADP-ribosylation factor
      (ARF) 6 regulates membrane recycling to regions of plasma membrane remodeling via
      the endocytic pathway. Here, we show that GTP-bound ARF6 interacts with Sec10, a
      subunit of the exocyst complex involved in docking of vesicles with the plasma
      membrane. We found that Sec10 localization in the perinuclear region is not
      restricted to the trans-Golgi network, but extends to recycling endosomes. In
      addition, we report that depletion of Sec5 exocyst subunit or dominant inhibition
      of Sec10 affects the function and the morphology of the recycling pathway. Sec10
      is found to redistribute to ruffling areas of the plasma membrane in cells
      expressing GTP-ARF6, whereas dominant inhibition of Sec10 interferes with ARF6
      induced cell spreading. Our paper suggests that ARF6 specifies delivery and
      insertion of recycling membranes to regions of dynamic reorganization of the
      plasma membrane through interaction with the vesicle-tethering exocyst complex.

PMID- 14662750
TI  - A Salmonella protein causes macrophage cell death by inducing autophagy.
AB  - Salmonella enterica, the causative agent of food poisoning and typhoid fever,
      induces programmed cell death in macrophages, a process found to be dependent on
      a type III protein secretion system, and SipB, a protein with membrane fusion
      activity that is delivered into host cells by this system. When expressed in
      cultured cells, SipB caused the formation of and localized to unusual
      multimembrane structures. These structures resembled autophagosomes and contained
      both mitochondrial and endoplasmic reticulum markers. A mutant form of SipB
      devoid of membrane fusion activity localized to mitochondria, but did not induce
      the formation of membrane structures. Upon Salmonella infection of macrophages,
      SipB was found in mitochondria, which appeared swollen and devoid of christae.
      Salmonella-infected macrophages exhibited marked accumulation of autophagic
      vesicles. We propose that Salmonella, through the action of SipB, kills
      macrophages by disrupting mitochondria, thereby inducing autophagy and cell
      death.

PMID- 14662751
TI  - Satellite cells attract monocytes and use macrophages as a support to escape
      apoptosis and enhance muscle growth.
AB  - Once escaped from the quiescence niche, precursor cells interact with stromal
      components that support their survival, proliferation, and differentiation. We
      examined interplays between human myogenic precursor cells (mpc) and
      monocyte/macrophages (MP), the main stromal cell type observed at site of muscle
      regeneration. mpc selectively and specifically attracted monocytes in vitro after
      their release from quiescence, chemotaxis declining with differentiation. A DNA
      macroarray-based strategy identified five chemotactic factors accounting for 77%
      of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1,
      fractalkine, VEGF, and the urokinase system. MP showed lower constitutive
      chemotactic activity than mpc, but attracted monocytes much strongly than mpc
      upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported
      amplification of monocyte recruitment. Determination of [3H]thymidine
      incorporation, oligosomal DNA levels and annexin-V binding showed that MP
      stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by
      direct contacts. We conclude that once activated, mpc, which are located close by
      capillaries, initiate monocyte recruitment and interplay with MP to amplify
      chemotaxis and enhance muscle growth.

PMID- 14662752
TI  - Peritoneal macrophages express both P-selectin and PSGL-1.
AB  - Macrophages, phagocytic cells involved in an early phase of host defense, are
      known to express the P-selectin ligand, PSGL-1. Heretofore, P-selectin has only
      been found on platelets and endothelial cells. Here, we demonstrate that
      peritoneal macrophages isolated by peritoneal lavage of unchallenged mice express
      P-selectin on the plasma membrane. The peritoneal macrophages synthesize P
      selectin, as indicated by metabolic labeling experiments. P-Selectin is
      constitutively expressed on the extracellular surface of macrophages but is only
      partially colocalized with PSGL-1. P-Selectin is rapidly translocated from the
      macrophage plasma membrane to intracellular vesicles and to lysosomes. Peritoneal
      macrophages assemble into cell strings under flow conditions based upon
      macrophage-macrophage interactions mediated by P-selectin and PSGL-1. This is the
      first description of a leukocyte shown to express both P-selectin and PSGL-1.

PMID- 14662753
TI  - The ubiquitin-related protein PLIC-1 regulates heterotrimeric G protein function
      through association with Gbetagamma.
AB  - PLIC-1, a newly described ubiquitin-related protein, inhibited both Jurkat
      migration toward SDF-1alpha and A431 wound healing, but the closely related PLIC
      2 did not. PLIC-1 prevented the SDF-1alpha-induced activation of phospholipase C,
      decreased ligand-induced internalization of SDF-1alpha receptor CXCR4 and
      inhibited chemotaxis signaled by a transfected Gi-coupled receptor. However, PLIC
      1 had no effect on Gs-mediated adenylyl cyclase activation, and inhibited only
      the Gbetagamma-dependent component of Gq-initiated increase in [Ca2+]i, which is
      consistent with selective inhibition of Gbetagamma function. PLIC-1 colocalized
      with G proteins in lamellae and pseudopods, and precipitated Gbetagamma in pull
      downs. Interaction with Gbetagamma did not require PLIC-1's ubiquitin-like or
      ubiquitin-associated domains, and proteasome inhibition had no effect on SDF
      1alpha activation of phospholipase C, indicating that PLIC-1's inhibition of
      Gbetagamma did not result from effects on proteasome function. Thus, PLIC-1
      inhibits Gi signaling by direct association with Gbetagamma; because it also
      interacts with CD47, a modulator of integrin function, it likely has a role
      integrating adhesion and signaling components of cell migration.

PMID- 14662754
TI  - EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5.
AB  - EWI-2, a cell surface immunoglobulin SF protein of unknown function, associates
      with tetraspanins CD9 and CD81 with high stoichiometry. Overexpression of EWI-2
      in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on
      laminin-5, and had no effect on reaggregation of cells plated on collagen I
      (alpha2beta1 integrin ligand). However, on laminin-5 (alpha3beta1 integrin
      ligand), A431 cell reaggregation and motility functions were markedly impaired.
      Immunodepletion and reexpression experiments revealed that tetraspanins CD9 and
      CD81 physically link EWI-2 to alpha3beta1 integrin, but not to other integrins.
      CD81 also controlled EWI-2 maturation and cell surface localization. EWI-2
      overexpression not only suppressed cell migration, but also redirected CD81 to
      cell filopodia and enhanced alpha3beta1-CD81 complex formation. In contrast, an
      EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to
      filopodia, or enhance alpha3beta1-CD81 complex formation. These results show how
      laterally associated EWI-2 might regulate alpha3beta1 function in disease and
      development, and demonstrate how tetraspanin proteins can assemble multiple
      nontetraspanin proteins into functional complexes.

PMID- 14662755
TI  - Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing.
AB  - ADAMTS-4 (a disintegrin and metalloprotease with thrombospondin motifs) is a
      multidomain metalloproteinase belonging to the reprolysin family. The enzyme
      cleaves aggrecan core protein at several sites. Here we report that the non
      catalytic ancillary domains of the enzyme play a major role in regulating
      aggrecanase activity, with the C-terminal spacer domain masking the general
      proteolytic activity. Expressing a series of domain deletion mutants in mammalian
      cells and examining their aggrecan-degrading and general proteolytic activities,
      we found that full-length ADAMTS-4 of 70 kDa was the most effective aggrecanase,
      but it exhibited little activity against the Glu(373)-Ala(374) bond, the site
      originally characterized as a signature of aggrecanase activity. Little activity
      was detected against reduced and carboxymethylated transferrin (Cm-Tf), a general
      proteinase substrate. However, it readily cleaved the Glu(1480)-Gly(1481) bond in
      the chondroitin sulfate-rich region of aggrecan. Of the constructed mutants, the
      C-terminal spacer domain deletion mutant more effectively hydrolyzed both the
      Glu(373)-Ala(374) and Glu(1480)-Gly(1481) bonds. It also revealed new activities
      against Cm-Tf, fibromodulin, and decorin. Further deletion of the cysteine-rich
      domain reduced the aggrecanase activity by 80% but did not alter the activity
      against Cm-Tf or fibromodulin. Further removal of the thrombospondin type I
      domain drastically reduced all tested proteolytic activities, and very limited
      enzymatic activity was detected with the catalytic domain. Full-length ADAMTS-4
      binds to pericellular and extracellular matrix, but deletion of the spacer domain
      releases the enzyme. ADAMTS-4 lacking the spacer domain has promiscuous substrate
      specificity considerably different from that previously reported for aggrecan
      core protein. Finding of ADAMTS-4 in the interleukin-1alpha-treated porcine
      articular cartilage primarily as a 46-kDa form suggests that it exhibits a
      broader substrate spectrum in the tissue than originally considered.

PMID- 14662756
TI  - A monooxygenase catalyzes sequential dechlorinations of 2,4,6-trichlorophenol by
      oxidative and hydrolytic reactions.
AB  - Ralstonia eutropha JMP134 2,4,6-trichlorophenol (2,4,6-TCP) 4-monooxygenase
      catalyzes sequential dechlorinations of 2,4,6-TCP to 6-chlorohydroxyquinol.
      Although 2,6-dichlorohydroxyquinol is a logical metabolic intermediate, the
      enzyme hardly uses it as a substrate, implying it may not be a true intermediate.
      Evidence is provided to support the proposition that the monooxygenase oxidized
      2,4,6-TCP to 2,6-dichloroquinone that remained with the enzyme and got hydrolyzed
      to 2-chlorohydroxyquinone, which was chemically reduced by ascorbate and NADH to
      6-chlorohydroxyquinol. When the monooxygenase oxidized 2,6-dichlorophenol, the
      product was 2,6-dichloroquinol, which was not further converted to 6
      chlorohydroxyquinol, implying that the enzyme only converts 2,6-dichloroquinone
      to 6-chlorohydroxyquinol. Stoichiometric analysis indicated the consumption of
      one O2 molecule per 2,4,6-TCP converted to 6-chlorohydroxyquinol, ruling out the
      possibility of two oxidative reactions. Experiments with 18O-labeling gave direct
      evidence for the incorporation of oxygen from both O2 and H2O into the produced 6
      chlorohydroxyquinol. A monooxygenase that catalyzes hydroxylation by both
      oxidative and hydrolytic reactions has not been reported to date. The ability of
      the enzyme to perform two types of reactions is not due to the presence of a
      second functional domain but rather is due to catalytic promiscuity, as a
      homologous monooxygenase converts 2,4,6-TCP to only 2,6-dichloroquinol. Employing
      both conventional catalysis and catalytic promiscuity of a single enzyme in two
      consecutive steps of a metabolic pathway has been unknown previously.

PMID- 14662757
TI  - Exocytotic insertion of TRPC6 channel into the plasma membrane upon Gq protein
      coupled receptor activation.
AB  - TRPC proteins are the mammalian homologues of the Drosophila transient receptor
      potential channel and are involved in calcium entry after agonist stimulation of
      non-excitable cells. Seven mammalian TRPCs have been cloned, and their mechanisms
      of activation and regulation are still the subject of intense research. TRPC
      proteins interact with the inositol 1,4,5-trisphosphate receptor, and the
      conformational coupling plays a critical role in the activation of calcium entry.
      Some evidence also supports an exocytotic mechanism as part of the activation of
      calcium entry. To investigate the possible involvement of exocytosis in TRPC6
      activation, we evaluated the location of TRPC6 at the plasma membrane by
      biotinylation labeling of cell surface proteins and by indirect
      immunofluorescence marking of TRPC6 in stably transfected HEK 293 cells. We
      showed that when the muscarinic receptor was stimulated or the thapsigargin
      induced intracellular calcium pool was depleted the level of TRPC6 at the plasma
      membrane increased. The carbachol concentration at which TRPC6 externalization
      occurred was lower than the concentration required to activate TRPC6.
      Externalization occurred within the first 30 s of stimulation, and TRPC6 remained
      at the plasma membrane as long as the stimulus was present. These results
      indicate that an exocytotic mechanism is involved in the activation of TRPC6.

PMID- 14662758
TI  - Changes in the expression of many Ets family transcription factors and of
      potential target genes in normal mammary tissue and tumors.
AB  - Interfering with Ets transcription factor function reverses multiple aspects of
      the transformed phenotype of mouse or human tumor cells. However, the unknown
      number of individual Ets factors expressed in any cellular context and the
      similar DNA binding specificities of Ets family members complicates the
      identification of those that mediate transformation. By utilizing quantitative
      PCR assays for 25 mouse Ets factors, we analyzed the expression of essentially
      the entire Ets family in normal mammary tissue, mammary-related cell lines, and
      mammary tumors. In normal mammary tissue, 24 Ets factors were expressed. Even
      clonal derived cell lines expressed 14-20 Ets members. The most abundant Ets
      factor mRNAs measured in normal mammary tissue were Elk4, Elf1, and Ets2.
      Subtractive analysis of mammary tissue identified which Ets factors were
      predominantly expressed in the myeloid/lymphoid or epithelial cell compartments.
      Comparison of Ets factor expression in normal mammary tissue and mammary tumors
      identified significantly elevated expression of Pse/PDEF, Ese2/Elf5, Ese3/Ehf,
      TEL/Etv6, and Elf2/NERF in mammary tumors and confirmed previously reported
      alterations in expression of Ese1/Elf3 and the PEA3 subfamily. Expression of 13
      Ets target genes, implicated in various aspects of tumor progression, was also
      analyzed. Altered expression of particular Ets target genes was significantly
      correlated with particular Ets factors (e.g. maspin and Ese2), suggesting
      specific in vivo regulatory roles. Together, this comprehensive analysis revealed
      unexpectedly diverse Ets family gene expression, characterized novel Ets factor
      changes in mammary tumors, and implicated specific Ets factors in the regulation
      of multiple genes involved in mammary tumor progression.

PMID- 14662759
TI  - Overexpression of MEKK3 confers resistance to apoptosis through activation of
      NFkappaB.
AB  - Many cancers have constitutively activated NFkappaB, the elevation of which
      contributes to cancer cell resistance to chemotherapeutic agent-induced
      apoptosis. Although mitogen-activated protein kinase/extracellular-regulated
      kinase kinase kinase-3 (MEKK3) has been shown to participate in the activation of
      NFkappaB, its relations to apoptosis and cancer are unclear. In this study, we
      established cell model systems to examine whether stable expression of MEKK3
      could lead to increased NFkappaB activity and confer resistance to apoptosis. In
      addition, we investigated in breast and ovarian cancers whether MEKK3 expression
      may be altered and correlated with aberrant NFkappaB activity. We show that
      stable cell lines overexpressing MEKK3 not only had elevated levels of NFkappaB
      binding activity but also were more responsive to cytokine stimulation. These
      stable cells showed 2-4-fold higher basal expression of Bcl-2 and xIAP than the
      parental cells. Consistent with this increased expression of cell survival genes,
      MEKK3 stable cells showed reduced activation of caspases 3 and 8 and poly(ADP
      ribose) polymerase cleavage and dramatically increased resistance to apoptosis
      induced by tumor necrosis factor-related apoptosis-inducing ligand, doxorubicin,
      daunorubicin, camptothecin, and paclitaxel. Intriguingly, analysis of human
      breast and ovarian cancers showed that a significant fraction of these samples
      have elevated MEKK3 protein levels with corresponding increases in NFkappaB
      binding activities. Thus, our results established that elevated expression of
      MEKK3 appears to be a frequent occurrence in breast and ovarian cancers and that
      overexpression of MEKK3 in cells leads to increased NFkappaB activity and
      increased expression of cell survival factors and ultimately contributes to their
      resistance to apoptosis. As such, MEKK3 may serve as a therapeutic target to
      control cancer cell resistance to cytokine- or drug-induced apoptosis.

PMID- 14662760
TI  - A role for iron in an ancient carbonic anhydrase.
AB  - Since 1933, carbonic anhydrase research has focused on enzymes from mammals
      (alpha class) and plants (beta class); however, two additional classes (gamma and
      delta) were discovered recently. Cam, from the procaryote Methanosarcina
      thermophila, is the prototype of the gamma class and the first carbonic anhydrase
      to be characterized from either an anaerobic organism or the Archaea domain. All
      of the enzymes characterized from the four classes have been purified aerobically
      and are reported to contain a catalytic zinc. Herein, we report the anaerobic
      reconstitution of apo-Cam with Fe2+, which yielded Cam with an effective kcat
      that exceeded that for the Zn2+-reconstituted enzyme. Mossbauer spectroscopy
      showed that the Fe2+-reconstituted enzyme contained high spin Fe2+ that, when
      oxidized to Fe3+, inactivated the enzyme. Reconstitution with Fe3+ was
      unsuccessful. Reconstitution with Cu2+, Mn2+, Ni2+, or Cd2+ yielded enzymes with
      effective kcat values that were 10% or less than the value for the Zn2+
      reconstituted Cam. Cam produced in Escherichia coli and purified anaerobically
      contained iron with effective kcat and kcat/Km values exceeding the values for
      Zn2+-reconstituted Cam. The results identify a previously unrecognized biological
      function for iron.

PMID- 14662761
TI  - Effects of oxygen and light intensity on transcriptome expression in Rhodobacter
      sphaeroides 2.4.1. Redox active gene expression profile.
AB  - The roles of oxygen and light on the regulation of photosynthesis gene expression
      in Rhodobacter sphaeroides 2.4.1 have been well studied over the past 50 years.
      More recently, the effects of oxygen and light on gene regulation have been shown
      to involve the interacting redox chains present in R. sphaeroides under diverse
      growth conditions, and many of the redox carriers comprising these chains have
      been well studied. However, the expression patterns of those genes encoding these
      redox carriers, under aerobic and anaerobic photosynthetic growth, have been less
      well studied. Here, we provide a transcriptional analysis of many of the genes
      comprising the photosynthesis lifestyle, including genes corresponding to many of
      the known regulatory elements controlling the response of this organism to oxygen
      and light. The observed patterns of gene expression are evaluated and discussed
      in light of our knowledge of the physiology of R. sphaeroides under aerobic and
      photosynthetic growth conditions. Finally, this analysis has enabled to us go
      beyond the traditional patterns of gene expression associated with the
      photosynthesis lifestyle and to consider, for the first time, the full complement
      of genes responding to oxygen, and variations in light intensity when growing
      photosynthetically. The data provided here should be considered as a first step
      in enabling one to model electron flow in R. sphaeroides 2.4.1.

PMID- 14662762
TI  - A novel hydrogen peroxide-induced phosphorylation and ubiquitination pathway
      leading to RNA polymerase II proteolysis.
AB  - DNA damage-induced ubiquitination of the largest subunit of RNA polymerase II,
      Rpb1, has been implicated in transcription-coupled repair for years. The studies
      so far, however, have been limited to the use of bulky helix-distorting DNA
      damages caused by UV light and cisplatin, which are corrected by the nucleotide
      excision repair pathway. Non-bulky, non-helix-distorting damages are caused at
      high frequency by reactive oxygen species in cells and corrected by the base
      excision repair pathway. Contrary to a classic view, we recently found that the
      second type of DNA lesions also causes RNA polymerase II stalling in vitro. In
      this paper, we show that hydrogen peroxide (H(2)O(2)) causes significant
      ubiquitination and proteasomal degradation of Rpb1 by mechanisms that are
      distinct from those employed after UV irradiation. UV irradiation and H(2)O(2)
      treatment cause characteristic changes in protein kinases phosphorylating the
      carboxyl-terminal domain at Ser-2 and -5. The H(2)O(2)-induced ubiquitination is
      likely dependent on unusual Ser-5 phosphorylation by ERK1/2. Moreover, the
      H(2)O(2)-induced ubiquitination occurs on transcriptionally engaged polymerases
      without the help of Cockayne syndrome A and B proteins and von Hippel-Lindau
      tumor suppressor proteins, which are all required for the UV-induced
      ubiquitination. These results suggest that stalled polymerases are recognized and
      ubiquitinated differentially depending on the types of DNA lesions. Our findings
      may have general implications in the basic mechanism of transcription-coupled
      nucleotide excision repair and base excision repair.

PMID- 14662763
TI  - The identity of proteins associated with a small heat shock protein during heat
      stress in vivo indicates that these chaperones protect a wide range of cellular
      functions.
AB  - The small heat shock proteins (sHSPs) are a ubiquitous class of ATP-independent
      chaperones believed to prevent irreversible protein aggregation and to facilitate
      subsequent protein renaturation in cooperation with ATP-dependent chaperones.
      Although sHSP chaperone activity has been studied extensively in vitro,
      understanding the mechanism of sHSP function requires identification of proteins
      that are sHSP substrates in vivo. We have used both immunoprecipitation and
      affinity chromatography to recover 42 proteins that specifically interact with
      Synechocystis Hsp16.6 in vivo during heat treatment. These proteins can all be
      released from Hsp16.6 by the ATP-dependent activity of DnaK and co-chaperones and
      are heat-labile. Thirteen of the putative substrate proteins were identified by
      mass spectrometry and reveal the potential for sHSPs to protect cellular
      functions as diverse as transcription, translation, cell signaling, and secondary
      metabolism. One of the putative substrates, serine esterase, was purified and
      tested directly for interaction with purified Hsp16.6. Hsp16.6 effectively formed
      soluble complexes with serine esterase in a heat-dependent fashion, thereby
      preventing formation of insoluble serine esterase aggregates. These data offer
      critical insights into the characteristics of native sHSP substrates and extend
      and provide in vivo support for the chaperone model of sHSP function.

PMID- 14662764
TI  - Intermediates control domain swapping during folding of p13suc1.
AB  - The 13-kDa protein p13(suc1) has two folded states, a monomer and a structurally
      similar domain-swapped dimer formed by exchange of a beta-strand. The refolding
      reaction of p13(suc1) is multiphasic, and in this paper we analyze the kinetics
      as a function of denaturant and protein concentration and compare the behavior of
      wild type and a set of mutants previously designed with dimerization propensities
      that span 9 orders of magnitude. We show that the folding reactions of wild type
      and all mutants produce the monomer predominantly despite their very different
      equilibrium behavior. However, the addition of low concentrations of denaturant
      in the refolding buffer leads to thermodynamic control of the folding reaction
      with products that correspond to the wild type and mutant equilibrium
      dimerization propensities. We present evidence that the kinetic control in the
      absence of urea arises because of the population of the folding intermediates.
      Intermediates are usually considered to be detrimental to folding because they
      slow down the reaction; however, our work shows that intermediates buffer the
      monomeric folding pathway against the effect of mutations that favor the
      nonfunctional, dimeric state at equilibrium.

PMID- 14662766
TI  - HSP25 is involved in two steps of the differentiation of PAM212 keratinocytes.
AB  - HSP25 is a member of the small heat shock protein family. This 25-kDa protein
      exhibits a highly specific distribution during mouse embryonic development.
      Although multiple functions have been proposed for HSP25, the role it plays
      during differentiation is still unknown. High levels of HSP25 can be detected in
      embryonic and adult skin. During epidermis differentiation, the concentration of
      HSP25 increases with the distance of keratinocytes from the basal layer, in
      parallel with the extent of keratinization. We used an ex vivo cellular system,
      PAM212 cells, to analyze quantitatively and qualitatively the dynamics of HSP25
      production and phosphorylation during the differentiation of keratinocytes. Our
      observations suggest that HSP25 is involved in two steps of PAM212 keratinocyte
      differentiation. Shortly after the induction of differentiation, a transient
      hyperphosphorylation of HSP25 seems to be essential for the expression of
      differentiation markers. Later, the chaperone-active form of HSP25 is organized
      progressively into characteristic aggregates involved in the dynamics of keratin
      filament networks.

PMID- 14662765
TI  - ATP-citrate lyase deficiency in the mouse.
AB  - ATP-citrate lyase (Acly) is one of two cytosolic enzymes that synthesize acetyl
      coenzyme A (CoA). Because acetyl-CoA is an essential building block for
      cholesterol and triglycerides, Acly has been considered a therapeutic target for
      hyperlipidemias and obesity. To define the phenotype of Acly-deficient mice, we
      created Acly knockout mice in which a beta-galactosidase marker is expressed from
      Acly regulatory sequences. We also sought to define the cell type-specific
      expression patterns of Acly to further elucidate the in vivo roles of the enzyme.
      Homozygous Acly knockout mice died early in development. Heterozygous mice were
      healthy, fertile, and normolipidemic on both chow and high fat diets, despite
      expressing half-normal amounts of Acly mRNA and protein. Fibroblasts and
      hepatocytes from heterozygous Acly mice contained half-normal amounts of Acly
      mRNA and protein, but this did not perturb triglyceride and cholesterol synthesis
      or the expression of lipid biosynthetic genes regulated by sterol regulatory
      element-binding proteins. The expression of acetyl-CoA synthetase 1, another
      cytosolic enzyme for producing acetyl-CoA, was not up-regulated. As judged by
      beta-galactosidase staining, Acly was expressed ubiquitously but was expressed
      particularly highly in tissues with high levels of lipogenesis, such as in the
      livers of mice fed a high-carbohydrate diet. beta-Galactosidase staining was
      intense in the developing brain, in keeping with the high levels of de novo
      lipogenesis of the tissue. In the adult brain, beta-galactosidase staining was in
      general much lower, consistent with reduced levels of lipogenesis; however, beta
      galactosidase expression remained very high in cholinergic neurons, likely
      reflecting the importance of Acly in generating acetyl-CoA for acetylcholine
      synthesis. The Acly knockout allele is useful for identifying cell types with a
      high demand for acetyl-CoA synthesis.

PMID- 14662767
TI  - NMR solution structure of the focal adhesion targeting domain of focal adhesion
      kinase in complex with a paxillin LD peptide: evidence for a two-site binding
      model.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is regulated
      by integrins. Upon activation, FAK generates signals that modulate crucial cell
      functions, including cell proliferation, migration, and survival. The C-terminal
      focal adhesion targeting (FAT) sequence mediates localization of FAK to discrete
      regions in the cell called focal adhesions. Several binding partners for the FAT
      domain of FAK have been identified, including paxillin. We have determined the
      solution structure of the avian FAT domain in complex with a peptide mimicking
      the LD2 motif of paxillin by NMR spectroscopy. The FAT domain retains a similar
      fold to that found in the unliganded form when complexed to the paxillin-derived
      LD2 peptide, an antiparallel four-helix bundle. However, noticeable
      conformational changes were observed upon the LD2 peptide binding, especially the
      position of helix 4. Multiple lines of evidence, including the results obtained
      from isothermal titration calorimetry, intermolecular nuclear Overhauser effects,
      mutagenesis, and protection from paramagnetic line broadening, support the
      existence of two distinct paxillin-binding sites on the opposite faces of the FAT
      domain. The structure of the FAT domain-LD2 complex was modeled using the program
      HADDOCK based on our solution structure of the LD2-bound FAT domain and
      mutagenesis data. Our model of the FAT domain-LD2 complex provides insight into
      the molecular basis of FAK-paxillin binding interactions, which will aid in
      understanding the role of paxillin in FAK targeting and signaling.

PMID- 14662768
TI  - Kinetic interaction analysis of human interleukin 5 receptor alpha mutants
      reveals a unique binding topology and charge distribution for cytokine
      recognition.
AB  - Human interleukin 5 receptor alpha (IL5Ralpha) comprises three fibronectin type
      III domains (D1, D2, and D3) in the extracellular region. Previous results have
      indicated that residues in the D1D2 domains are crucial for high affinity
      interaction with human interleukin 5 (IL5). Yet, it is the D2D3 domains that have
      sequence homology with the classic cytokine recognition motif that is generally
      assumed to be the minimum cytokine-recognizing unit. In the present study, we
      used kinetic interaction analysis of alanine-scanning mutational variants of
      IL5Ralpha to define the residues involved in IL5 recognition. Soluble forms of
      IL5Ralpha variants were expressed in S2 cells, selectively captured via their C
      terminal V5 tag by anti-V5 tag antibody immobilized onto the sensor chip and
      examined for IL5 interaction by using a sandwich surface plasmon resonance
      biosensor method. Marked effects on the interaction kinetics were observed not
      only in D1 (Asp(55), Asp(56), and Glu(58)) and D2 (Lys(186) and Arg(188))
      domains, but also in the D3 (Arg(297)) domain. Modeling of the tertiary structure
      of IL5Ralpha indicated that these binding residues fell into two clusters. The
      first cluster consists of D1 domain residues that form a negatively charged
      patch, whereas the second cluster consists of residues that form a positively
      charged patch at the interface of D2 and D3 domains. These results suggest that
      the IL5 x IL5Ralpha system adopts a unique binding topology, in which the
      cytokine is recognized by a D2D3 tandem domain combined with a D1 domain, to form
      an extended cytokine recognition interface.

PMID- 14662769
TI  - Identification of RNA-binding proteins in RAW 264.7 cells that recognize a
      lipopolysaccharide-responsive element in the 3-untranslated region of the murine
      cyclooxygenase-2 mRNA.
AB  - RAW 264.7 cells rapidly induce cyclooxygenase-2 (COX-2) in response to
      lipopolysaccharide treatment. Part of the increased COX-2 expression occurred
      through post-transcriptional mechanisms mediated through specific regions of the
      3'-untranslated region (UTR) of the message. The proximal region of the 3'-UTR of
      COX-2 contains a highly conserved AU-rich element that was able to confer
      lipopolysaccharide regulation of a chimeric reporter-gene. Electrophoretic
      mobility shift assays demonstrated that the RNA-binding proteins TIAR, AUF1, HuR,
      and TIA-1 all form an RNA-protein complex with the first 60 nucleotides of the 3'
      UTR of COX-2. Biotinylated RNA probes were used to isolate additional proteins
      that bind the 3'-UTR of COX-2. We identified several RNA-binding proteins
      including TIAR, AUF1, CBF-A, RBM3, heterogeneous nuclear ribonucleoprotein
      (hnRNP) A3, and hnRNP A2/B1. We identified four alternatively spliced isoforms of
      AUF1 which migrated at multiple isoelectric points. Likewise, we identified
      alternatively spliced isoforms of CBF-A, hnRNP A3, and hnRNP A2/B1. Western
      analysis of two-dimensional gels identified multiple isoforms of TIA-1, TIAR, and
      AUF1 at pI values that spanned nearly 3 pH units. Thus, through a combination of
      alternative splicing and post-translational modification cells are able to
      increase greatly the repertoire of protein species expressed at a given time or
      in response to extracellular stimuli.

PMID- 14662770
TI  - Epidermal growth factor increases coactivation of the androgen receptor in
      recurrent prostate cancer.
AB  - Growth of normal and neoplastic prostate is mediated by the androgen receptor
      (AR), a ligand-dependent transcription factor activated by high affinity androgen
      binding. The AR is highly expressed in recurrent prostate cancer cells that
      proliferate despite reduced circulating androgen. In this report, we show that
      epidermal growth factor (EGF) increases androgen-dependent AR transactivation in
      the recurrent prostate cancer cell line CWR-R1 through a mechanism that involves
      a post-transcriptional increase in the p160 coactivator transcriptional
      intermediary factor 2/glucocorticoid receptor interacting protein 1 (TIF2/GRIP1).
      Site-specific mutagenesis and selective MAPK inhibitors linked the EGF-induced
      increase in AR transactivation to phosphorylation of TIF2/GRIP1. EGF signaling
      increased the coimmunoprecipitation of TIF2 and AR. AR transactivation and its
      stimulation by EGF were reduced by small interfering RNA inhibition of TIF2/GRIP1
      expression. The data indicate that EGF signaling through MAPK increases
      TIF2/GRIP1 coactivation of AR transactivation in recurrent prostate cancer.

PMID- 14662771
TI  - HLS5, a novel RBCC (ring finger, B box, coiled-coil) family member isolated from
      a hemopoietic lineage switch, is a candidate tumor suppressor.
AB  - Hemopoietic cells, apparently committed to one lineage, can be reprogrammed to
      display the phenotype of another lineage. The J2E erythroleukemic cell line has
      on rare occasions developed the features of monocytic cells. Subtractive
      hybridization was used in an attempt to identify genes that were up-regulated
      during this erythroid to myeloid transition. We report here on the isolation of
      hemopoietic lineage switch 5 (Hls5), a gene expressed by the monocytoid variant
      cells, but not the parental J2E cells. Hls5 is a novel member of the RBCC (Ring
      finger, B box, coiled-coil) family of genes, which includes Pml, Herf1, Tif
      1alpha, and Rfp. Hls5 was expressed in a wide range of adult tissues; however, at
      different stages during embryogenesis, Hls5 was detected in the branchial arches,
      spinal cord, dorsal root ganglia, limb buds, and brain. The protein was present
      in cytoplasmic granules and punctate nuclear bodies. Isolation of the human cDNA
      and genomic DNA revealed that the gene was located on chromosome 8p21, a region
      implicated in numerous leukemias and solid tumors. Enforced expression of Hls5 in
      HeLa cells inhibited cell growth, clonogenicity, and tumorigenicity. It is
      conceivable that HLS5 is one of the tumor suppressor genes thought to reside at
      the 8p21 locus.

PMID- 14662772
TI  - Role of multiple drug resistance protein 1 in neutral but not acidic
      glycosphingolipid biosynthesis.
AB  - Transfection studies have implicated the multiple drug resistance pump, MDR1, as
      a glucosyl ceramide translocase within the Golgi complex (Lala, P., Ito, S., and
      Lingwood, C. A. (2000) J. Biol. Chem. 275, 6246-6251). We now show that MDR1
      inhibitors, cyclosporin A or ketoconazole, inhibit neutral glycosphingolipid
      biosynthesis in 11 of 12 cell lines tested. The exception, HeLa cells, do not
      express MDR1. Microsomal lactosyl ceramide and globotriaosyl ceramide synthesis
      from endogenous or exogenously added liposomal glucosyl ceramide was inhibited by
      cyclosporin A, consistent with a direct role for MDR1/glucosyl ceramide
      translocase activity in their synthesis. In contrast, cellular ganglioside
      synthesis in the same cells, was unaffected by MDR1 inhibition, suggesting
      neutral and acid glycosphingolipids are synthesized from distinct precursor
      glycosphingolipid pools. Metabolic labeling in wild type and knock-out (MDR1a,
      1b, MRP1) mouse fibroblasts showed the same loss of neutral glycosphingolipid
      (glucosyl ceramide, lactosyl ceramide) but not ganglioside (GM3) synthesis,
      confirming the proposed role for MDR1 translocase activity. Cryo-immunoelectron
      microscopy showed MDR1 was predominantly intracellular, largely in rab6
      containing Golgi vesicles and Golgi cisternae, the site of glycosphingolipid
      synthesis. These studies identify MDR1 as the major glucosyl ceramide flippase
      required for neutral glycosphingolipid anabolism and demonstrate a previously
      unappreciated dichotomy between neutral and acid glycosphingolipid synthesis.

PMID- 14662773
TI  - Vacuolar H+-ATPase binding to microfilaments: regulation in response to
      phosphatidylinositol 3-kinase activity and detailed characterization of the actin
      binding site in subunit B.
AB  - Vacuolar H(+)-ATPase (V-ATPase) binds microfilaments, and that interaction may be
      mediated by an actin binding domain in subunit B of the enzyme. To test for
      possible physiologic functions of the actin binding activity of V-ATPase, early
      responses of resorbing osteoclasts to inhibition of phosphatidylinositol 3-kinase
      activity by wortmannin and LY294002 were examined. Rapid co-localization between
      V-ATPase and F-actin was demonstrated by immunocytochemistry, and corresponding
      association between V-ATPase and F-actin in immunoprecipitations and pelleting
      assays was detected. This response was reversed as osteoclasts recovered
      resorptive activity after inhibitors were removed. By expressing and
      characterizing fusion proteins containing segments of the actin-binding amino
      terminal regions of the B subunits of V-ATPase, we mapped the actin-binding site
      to a 44-amino acid domain. An 11-amino acid segment with a sequence similar to
      the actin-binding site of human profilin I was detected within this region. 13
      Mers containing these profilin-like segments bound actin in fluorescent
      anisotropy studies and competed with profilin for binding to actin. Using site
      directed mutagenesis, the 11-amino acid profilin-like actin-binding motifs (amino
      acids 49-59 of B1 and 55-65 of B2) were replaced with an 11-amino acid spacer
      with a sequence based on the homologous sequence from subunit B of Pyrococcus
      horikoshii, an organism that lacks an actin cytoskeleton. These substitutions
      eliminated the actin-binding activity of the B subunit fusion proteins. In
      summary, binding between V-ATPase and F-actin in osteoclasts occurs in response
      to blocking phosphatidylinositol 3-kinase activity. This response was fully
      reversible. The actin binding activities of the B subunits of V-ATPase required
      11-amino acid actin-binding motifs that are similar in sequence to the actin
      binding site of mammalian profilin I.

PMID- 14662774
TI  - Expression of NAG-1, a transforming growth factor-beta superfamily member, by
      troglitazone requires the early growth response gene EGR-1.
AB  - Troglitazone (TGZ) and 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) are
      peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands that have
      been shown to possess pro-apoptotic activity in human colon cancer. Although
      these compounds bind to PPARgamma transcription factors as agonists, emerging
      evidence suggests that TGZ acts independently of PPARgamma in many functions,
      including apoptosis. We previously reported that TGZ induces an early growth
      response transcription factor (EGR-1) by the ERK phosphorylation pathway rather
      than by the PPARgamma pathway (Baek, S. J., Wilson, L. C., Hsi, L. C., and Eling,
      T. E. (2003) J. Biol. Chem. 278, 5845-5853). In this report, we show that the
      expression of the antitumorigenic and/or pro-apoptotic gene NAG-1 (nonsteroidal
      anti-inflammatory drug-activated gene-1) is induced by TGZ and correlates with
      EGR-1 induction. In cotransfection and gel shift assays, we show that EGR-1
      binding sites are located within region -73 to -51 of the NAG-1 promoter and have
      an important role in the transactivation of TGZ-induced NAG-1 expression. In
      contrast, PGJ2 induced NAG-1 protein expression, but PGJ2 may not affect the same
      region that TGZ does in the NAG-1 promoter. The effect of PGJ2 is probably
      PPARgamma-dependent because a PPARgamma antagonist inhibited the PGJ2-induced
      expression of NAG-1. TGZ-induced NAG-1 expression was not inhibited by the
      PPARgamma antagonist. The fact that TGZ-induced NAG-1 expression was accompanied
      by the biosynthesis of EGR-1 also suggests that EGR-1 plays a pivotal role in TGZ
      induced NAG-1 expression. Our results suggest that EGR-1 induction is a unique
      property of TGZ, but is independent of PPARgamma activation. The up-regulation of
      NAG-1 may provide a novel explanation for the antitumorigenic property of TGZ.

PMID- 14662775
TI  - Ectopic expression of bovine type 5 phosphodiesterase confers a renal phenotype
      in Drosophila.
AB  - cGMP signaling regulates epithelial fluid transport by Drosophila Malpighian
      (renal) tubules. In order to directly evaluate the importance of cGMP-degrading
      phosphodiesterases (PDEs) in epithelial transport, bovine PDE5 (a bona fide cGMP
      PDE), was ectopically expressed in vivo. Transgenic UAS-PDE5 Drosophila were
      generated, and PDE5 expression was driven in specified tubule cells in vivo by
      cell-specific GAL4 drivers. Targeted expression was verified by PCR and Western
      blotting. Immunolocalization of PDE5 in tubule confirmed specificity of
      expression and demonstrated localization to the apical plasma membrane. GAL4/UAS
      PDE5 tubules exhibit increased cG-PDE activity and reduced basal cGMP levels
      compared with control lines. We show that wild-type and control tubules are
      sensitive to the PDE5-specific inhibitor sildenafil and that GAL4/UAS-PDE5
      tubules display enhanced sensitivity to sildenafil, compared with controls. cGMP
      content in GAL4/UAS-PDE5 tubules is restored to control levels by treatment with
      sildenafil. Thus bovine PDE5 retains cGMP-degrading activity and inhibitor
      sensitivity when expressed in Drosophila. Expression of PDE5 in tubule principal
      cells results in an epithelial phenotype, reducing rates of basal and cGMP
      /Cardioaccelatory peptide(2b)(CAP(2b))-stimulated fluid transport. Furthermore,
      inhibition of PDE5 activity by sildenafil restores basal and cGMP-stimulated
      fluid transport rates to control levels. However, corticotrophin releasing factor
      like-stimulated transport, which is activated by cAMP signaling, was unaffected,
      confirming that only cGMP-stimulated signaling events in tubule are compromised
      by overexpression of PDE5. Successful ectopic expression of a vertebrate cG-PDE
      in Drosophila has shown that cG-PDE has a critical role in tubule function in
      vivo and that cG-PDE function is conserved across evolution. The transgene also
      provides a generic tool for the analysis of cGMP signaling in Drosophila.

PMID- 14662776
TI  - The cardiac determination factor, Nkx2-5, is activated by mutual cofactors GATA-4
      and Smad1/4 via a novel upstream enhancer.
AB  - The mammalian homologue of Drosophila tinman, Nkx2-5, plays an early role in
      regulating cardiac genes and morphogenesis. Bone morphogenetic proteins (BMPs),
      members of the transforming growth factor (TGF)-beta family of signaling
      molecules, are involved in numerous developmental processes. BMP signaling is
      crucial in the regulation of Nkx2-5 expression and specification of the cardiac
      lineage. Constitutively active BMP type I receptor or the downstream pathway
      components and DNA-binding transcription factors, Smad1/4 directly activated Nkx2
      5 gene transcription. We identified and characterized a novel upstream Nkx2-5
      enhancer, composed of clustered repeats of Smad and GATA DNA binding sites. This
      composite Nkx2-5 enhancer was a direct target of BMP signaling via cooperative
      interactions between the downstream transducers Smad1/4 and GATA-4. In mammalian
      two hybrid assays, Smad factors recruited the hybrid gene GATA4-VP16 to strongly
      drive transcription of a reporter gene containing multimerized Smad binding sites
      These cofactors interacted through the second zinc finger and adjacent basic
      domain of GATA-4 and the N-terminal domain of Smads. Smad4 and GATA4 were also
      found to bind in vivo with the Nkx2-5 composite enhancer, as revealed by
      chromatin immunoprecipitation analysis of differentiated P19 cells. Finally,
      transgenic mice containing the Smad/GATA composite enhancer recapitulated early
      murine Nkx2-5 cardiac expression and deletion of this enhancer within a 10-kb
      transgene pBS-Nkx2-5 LacZ significantly reduced expression in the cardiac
      crescent. Thus, integration of GATA transcription factors with BMP signaling,
      through co-association with Smads factors, may initiate early Nkx2-5 expression;
      suggesting a vital role for the combination of these factors in the specification
      of cardiac progenitors.

PMID- 14662778
TI  - Twin autonomy.

PMID- 14662779
TI  - Role of oxidative stress and antioxidants in andrology and assisted reproductive
      technology.

PMID- 14662780
TI  - Semen analysis: are 2 counts truly better than 1?

PMID- 14662782
TI  - High levels of sperm DNA denaturation as the sole semen abnormality in a patient
      after chemotherapy for testis cancer.

PMID- 14662783
TI  - Penile necrosis in end-stage renal disease.

PMID- 14662784
TI  - Vasectomy influences expression of HE1 but not HE2 and HE5 genes in human
      epididymis.
AB  - Epididymal roles include protection and transport, maturation, and storage of the
      sperm cells. It is known that these functions are altered under vasectomy, but
      the consequences of excurrent duct obstruction on the pattern of gene expression
      along the human epididymis are poorly documented. In order to understand how
      excurrent duct occlusion affects different epididymal regions, the expression
      pattern of genes known to be expressed in specific epididymal segments was
      investigated along the epididymides of vasectomized men. Selected human
      epididymal complementary DNAs (cDNAs) identified by differential library
      screening were studied because of their unique messenger RNA (mRNA) distribution
      along the different epididymal segments. In situ hybridization as well as
      immunohistologic studies were undertaken to investigate the effect of vasectomy
      on a gene expressed all along the epididymis (HE1) or more selectively in the
      proximal (HE2) or distal (HE5) segment. The HE1 transcript was affected by the
      obstruction of the epididymis with little or no mRNA detectable along the
      epididymis. The HE1-related antigen was shown by immunohistochemical methods to
      be reduced within the epithelium of the epididymis of vasectomized men. By
      contrast, HE5 mRNA and protein, expressed in epithelial cells of the distal
      epididymis, were not affected by the obstruction of the vas deferens. Similarly,
      HE2 transcriptional and translational products normally expressed in the caput
      epididymidis were not affected by vasectomy. These results show that excurrent
      duct obstruction differentially affects the expression pattern of some specific
      transcripts and their encoded proteins, probably impairing their fundamental
      roles in the physiology of the epididymis.

PMID- 14662785
TI  - Seminal antioxidant capacity in pre- and postoperative varicocele.
AB  - In order to explore the impact of surgical treatment on antioxidant defense
      system in varicocele (VAR), we evaluated seminal total antioxidant capacity (TAC)
      in 25 patients affected by VAR, in 14 patients studied 10-24 months after
      varicocelectomy (post-VAR) and separated into normo- and oligospermic groups, and
      in 24 non-VAR control patients with seminal parameters matched to patients with
      VAR in the oligo- and normospermic groups (7 subjects with idiopathic
      oligospermia and 17 normal fertile subjects). TAC was measured in seminal plasma
      with the system H(2)O(2)-metamyoglobin as a source of radicals, which interact
      with a chromogen 2,2',-azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS),
      generating a radical cation spectroscopically detectable. The presence of
      antioxidants induces a lag time in the production of ABTS cation proportional to
      the concentration of antioxidant compounds. When whole groups of patients were
      analyzed, lag values were significantly higher in VAR vs non-VAR controls (mean
      +/- SEM, 106.6 +/- 8.8 seconds vs 78.7 +/- 8.8 seconds) but were not modified by
      surgery (mean +/- SEM, 105.8 +/- 8.6 seconds). In groups separated according to
      seminal parameters, oligospermic VAR presented significantly higher lag values
      than oligospermic controls. Finally, when exploring a possible association of TAC
      with seminal parameters, we found a significant correlation between lag and sperm
      motility only in patients with VAR who were in the normospermic group (r = 0.65,
      P <.01). This correlation was not yet manifest post-VAR. In conclusion, surgical
      treatment does not seem to modify absolute values of TAC but influences its fine
      regulation and relationships with sperm motility.

PMID- 14662786
TI  - Smooth muscle cell behavior in the ventral prostate of castrated rats.
AB  - Smooth muscle cells (SMC) play roles in prostatic development and function. The
      cells also respond to tissue injury and hormonal variations, alternating between
      a fully differentiated and contractile phenotype and a dedifferentiated synthetic
      or secretory phenotype. However, the phenotypic changes in SMC after androgen
      deprivation have not yet been described. The ventral prostate of control and
      castrated rats was processed for routine histology, immunocytochemistry, reverse
      transcriptase polymerase chain reaction (RT-PCR), and scanning electron
      microscopy (SEM). The maintenance of SMC phenotype was confirmed by
      immunocytochemistry and by RT-PCR. Stereological analyses were done to define the
      relative and absolute volume of the SMC. SMC were elongated and flattened against
      the epithelium. After castration, the cells shortened concomitantly with pleating
      of the cell surface, leading to a spinous aspect. SEM showed that the smooth
      surface of SMC became progressively folded. Immunocytochemistry demonstrated both
      smooth muscle myosin heavy chain and smooth muscle alpha-actin in the prostatic
      SMC 21 days after castration, whereas RT-PCR amplified the message for
      smoothelin. Stereological analysis showed an increase in the relative volume of
      SMC in relation to the whole gland and the stroma. A decrease in the absolute
      volume of SMC occurred only within the first 7 days after castration and remained
      unchanged thereafter. The prostatic SMC are affected by the absence of androgens
      and there is a critical transition point during the first week in which the total
      volume occupied by SMC diminished. The remaining SMC showed a marked phenotypical
      change. These findings indicate that ventral prostate SMC maintain their
      differentiated phenotype after castration. The alterations in SMC behavior
      correlate with general stromal modifications taking place after castration.

PMID- 14662787
TI  - Functional analysis of the cooled rat testis.
AB  - Direct cooling of the testis results in the depletion of most germ cells in vivo.
      Germ cell-depleted testes are now commonly used to investigate spermatogenic
      regeneration and can serve as recipients for germ cell transplantation. The
      present study explored the effects of cooling rat testes on the depletion of
      endogenous germ cells, spermatogenic regeneration, and Sertoli cell function.
      Adult rat testes were cooled with iced Ringer's solution for 60 minutes, which
      results in the initiation of apoptotic germ cell loss within 8 hours. Pachytene
      spermatocytes at stages XII-I were the cells most sensitive to cooling. In 46%
      67% of seminiferous tubule cross-sections, only Sertoli cells remained in the
      cooled testes 3-10 weeks after treatment. Germ cell loss was accompanied by a
      significant decrease in circulating inhibin B and an increase in follicle
      stimulating hormone concentrations, which indicated a change in Sertoli cell
      function. Quantitative analysis of mRNA expression associated with apoptotic
      signals showed no significant uniform changes among the cooled testes, although
      some individuals had a distinct up-regulation of FAS mRNA at 24 hours. Attempts
      to use the cooled testes as recipient testes for mouse-to-rat germ cell
      transplantation were undertaken, but none of the mouse germ cells transplanted
      into the testes 15-34 days after cooling appeared to have undergone
      spermatogenesis 64-92 days after transplantation. These data suggest that
      modifications to Sertoli cell function resulting from testicular cooling create
      an environment that is unable to support spermatogenesis by donor germ cells.

PMID- 14662788
TI  - Postnatal development and regulation of beta-hexosaminidase in epithelial cells
      of the rat epididymis.
AB  - beta-Hexosaminidase (Hex) catalyzes the hydrolysis of terminal sugar residues
      from a number of substrates such as GM2 gangliosides, glycoproteins, glycolipids,
      and glycosaminoglycans. As an enzyme present in lysosomes of epithelial cells of
      the adult rat epididymis, it serves to degrade substances endocytosed from the
      epididymal lumen. In this way, it modifies and creates a luminal environment
      where sperm can undergo their maturational modifications. In this study, the
      postnatal developmental pattern of expression of Hex was examined in animals from
      days 7-56. In addition, the role of testicular factors on Hex expression in the
      different cell types and regions of the epididymis of adult rats was examined in
      orchidectomized and efferent duct-ligated rats. Both parameters were examined on
      Bouin-fixed epididymides in conjunction with light microscope
      immunocytochemistry. At postnatal day 7, the epithelium of the entire epididymis
      was unreactive for anti-Hex antibody. By day 21, narrow and clear cells of their
      respective regions became reactive, whereas basal cells became reactive only by
      day 29. Principal cells displayed only an occasional reactive lysosome at day 21,
      several by day 29, and numerous reactive lysosomes by day 39, comparable to the
      region-specific distribution noted for 90-day-old animals, and at an age when
      high androgen levels are attained. Thus, postnatal onset of Hex expression varies
      according to the different cell types of the epididymis, suggesting different
      regulatory factors. This finding was confirmed from studies employing adult
      orchidectomized and efferent duct-ligated adult rats. Indeed, in all experimental
      animals, Hex immunostaining in narrow, clear, and basal cells was intense and
      comparable to control animals. In contrast, there was a notable absence of
      lysosomal staining in principal cells at all time points after orchidectomy,
      which was restored, however, following testosterone replacement. No effect on Hex
      expression was observed in efferent duct-ligated animals. Taken together, the
      data suggest that Hex expression in lysosomes of principal cells is regulated by
      testosterone or one of its metabolites. However, the expression of Hex being
      independent of testicular factors in narrow, clear, and basal cells of adult
      animals, but occurring at different time points during postnatal development,
      suggests that different regulatory factors are responsible for onset of Hex
      expression in these cell types during development.

PMID- 14662789
TI  - [Re: Postnatal development and regulation of beta-hexosaminidase in epithelial
      cells of the rat epididymis].

PMID- 14662790
TI  - Increased expression of estrogen receptor beta in pachytene spermatocytes after
      short-term methoxyacetic acid administration.
AB  - Degeneration of primary spermatocytes by apoptosis occurs during normal
      spermatogenesis, as well as in several pathological conditions, including
      exposure to specific testicular toxicants. The mechanisms that regulate the death
      and survival of primary spermatocytes, however, are still not well understood.
      The recent localization of estrogen receptor beta (ERbeta) and P450 aromatase in
      pachytene spermatocytes suggests a role for estrogens in this step of
      spermatogenesis. Using a well-known model of pachytene spermatocyte apoptosis in
      adult rats consisting of the administration of methoxyacetic acid (MAA), we
      investigated the participation of ERbeta during the initial phase of apoptosis,
      prior to germ cell loss. Adult rats were treated with a single intraperitoneal
      dose of MAA, and DNA laddering analysis confirmed apoptotic cell death in the
      testis. In enriched germ cell fractions and testis from MAA-treated animals,
      ERbeta mRNA increased significantly at 3 and 6 hours, respectively. Next, stage
      specific induction of ERbeta mRNA was demonstrated by use of laser capture
      microdissection of seminiferous tubules in combination with semiquantitative
      reverse transcription-polymerase chain reaction. The ERbeta protein also
      increased significantly after 6 hours and was mainly immunolocalized in the
      cytoplasm of pachytene spermatocytes of afflicted tubules. The cytoplasmic
      localization was confirmed by Western blot analysis of isolated cytoplasmic and
      nuclear fractions of testicular extracts. Finally, the MAA activation of ERbeta
      was tested in vitro in HepG2 cells cotransfected with ERbeta and a reporter
      construct that contained a consensus estrogen responsive element. Addition of MAA
      at similar doses used in vivo elicited a similar estrogenic activation as did
      estradiol at 1 nmol/L concentration. The present results raise the possibility
      that cytoplasmic ERbeta participates in the apoptotic process of pachytene
      spermatocytes induced by MAA. Whether MAA interacts with ERbeta in the cytoplasm
      of primary spermatocytes, preventing the progression of the first meiotic
      division, however, remains to be determined.

PMID- 14662791
TI  - Preservation of spermatogenesis in spinal cord injured rats with exogenous
      testosterone. Relationship with serum testosterone levels and cellular
      localization of cAMP responsive element modulator.
AB  - The current experiment examined the effects of exogenous testosterone (T) on
      spermatogenesis in rats with spinal cord injury (SCI) and their relationship with
      the cellular distribution of a cyclic AMP-responsive element modulator (CREM) in
      testicular cells. Implantation of T-filled Silastic capsules (TCs, 1-20 cm)
      resulted in dose-dependent, biphasic changes in testicular T levels and
      spermatogenesis in SCI rats. However, dose responsiveness of spermatogenesis to
      exogenous T in SCI rats differed from that in sham control rats. Specifically,
      implantation of 2-cm TCs enhanced the effects of SCI on spermatogenesis,
      resulting in total regression of the seminiferous epithelium. Although 3-cm TCs
      maintained complete spermatogenesis in sham control rats, this regimen failed to
      support complete spermatogenesis in SCI rats. Although complete spermatogenesis
      was maintained in SCI rats given 5-20-cm TC implants, various abnormalities
      persisted. Cellular distribution of CREM remained normal in SCI rats but was
      altered in those SCI rats that received 3- or 5-cm TC implants. Such effects were
      associated with reduced CREM proteins in testicular tissues. These results were
      consistent with altered cAMP signaling and its regulation in testicular cells
      after SCI and provided possible mechanistic explanations for the effects of SCI
      on spermatogenesis. CONCLUSION: SCI resulted in changes in the responsiveness of
      spermatogenesis to exogenous T. These effects were associated with altered
      cAMP/CREM signaling in testicular cells. Further studies, including a study of
      the relationship between serum T levels and normalcy of sperm functions and the
      role of neural-endocrine interactions in mediating the effects of SCI on
      spermatogenesis and sperm function, are needed so that therapeutic regimens can
      be designed for clinical use.

PMID- 14662792
TI  - Semen quality of men with asymptomatic chlamydial infection.
AB  - We have shown previously that the in vitro exposure of spermatozoa to elementary
      bodies (EBs) of Chlamydia trachomatis can lead to sperm death over a number of
      hours of incubation. As such, we have hypothesized that the ejaculates of men
      with a chlamydial infection could contain increased numbers of nonmotile (dead)
      spermatozoa if they are exposed to EBs prior to ejaculation. To test this
      hypothesis, the ejaculates of 642 men undergoing diagnostic semen analysis as
      part of ongoing infertility investigations with their partner were examined. All
      men were without symptoms of genitourinary infections and semen analysis was
      performed according to World Health Organisation (WHO) 1999 methods after a 3-5
      day abstinence period. In addition to semen analysis, nested plasmid polymerase
      chain reaction (PCR) was undertaken on the ejaculate to detect the presence of C
      trachomatis DNA. A total of 31 semen specimens (4.9%) were found to be positive,
      and in 28 of these, the diagnosis was confirmed using the ligase chain reaction
      (LCR). Men whose ejaculates were PCR positive for chlamydial DNA had a
      significantly (P <.05) higher mean concentration of leukocytes (1.71 +/- 2.20 x
      10(6) per mL) and a higher mean ejaculate volume (3.45 +/- 1.52 mL) than in those
      whose ejaculates were PCR negative (leukocyte concentration: 0.67 +/- 2.59 x
      10(6) per mL; volume 2.93 +/- 1.38 mL). Leukocytospermia was twice as common in
      men that were PCR positive for chlamydial DNA (P <.05) but it was not always
      associated with the presence of chlamydial DNA in semen. However, there was no
      difference in the mean percent motility between the 2 groups and the proportion
      of asthenozoospermia also did not differ. Because these results do not confirm
      the hypothesis proposed from our in vitro experiments, further work needs to be
      undertaken to understand whether human spermatozoa are actually exposed to
      elementary bodies of C trachomatis in an infected individual prior to
      ejaculation.

PMID- 14662793
TI  - Sex chromosome alignment at meiosis of azoospermic men with azoospermia factor
      microdeletion.
AB  - Deletions in the q arm of the Y chromosome result in spermatogenesis impairment.
      The aim of the present study was to observe the X and Y chromosome alignment in
      the spermatocytes of men with Y chromosome microdeletion of the azoospermia
      factor (AZF) region. This was performed by multicolor fluorescence in situ
      hybridization probes for the centromere and telomere regions. Testicular biopsies
      were performed in a testicular sperm extraction-intracytoplasmic sperm injection
      set-up in 11 azoospermic men: 8 (nonobstructive) with AZF deletions and 3
      (obstructive) controls. Histological sections, cytology preparations of the
      testicular biopsies, and evaluation of the meiosis according to the percentage of
      XY and 18 bivalents formation were assessed. Spermatozoa were identified in at
      least one location in controls and specimens with AZFc-deleted Y chromosomes.
      Complete spermatocyte arrest was found in those with a deletion that included the
      entire AZFb region. Bivalent formation rate of chromosome 18 was high in all
      samples (81%-99%). In contrast, the rate of bivalent X-Y as determined by
      centromeric probes was lower but in the range favorable with spermatozoa findings
      in controls and patients with the AZFc deletion (56%-90%), but not in those with
      AZFb-c deletions (28%-29%). A dramatic impairment in the normal alignment of X
      and Y telomeres in the specimen with AZFb-c deletion was shown (29%), compared to
      the specimens with AZFc deletion (70%-94%). It is suggested that the absence of
      sperm cells in specimens with the entire AZFb and with AZFb-c deletions is
      accompanied by meiosis impairment, perhaps as a result of the extent of the
      deletion or because of the absence of genes that are involved in the X and Y
      chromosome alignment.

PMID- 14662794
TI  - Lack of voltage-dependent calcium channel opening during the calcium influx
      induced by progesterone in human sperm. Effect of calcium channel deactivation
      and inactivation.
AB  - Progesterone induces calcium influx and acrosomal exocytosis in human sperm.
      Pharmacologic evidence suggests that voltage-dependent calcium channels (VDCCs)
      are involved. In this study, membrane potential (Vm) and intracellular calcium
      concentration ([Ca(2+)](i)) were monitored simultaneously to assess the effect of
      VDCC gating on the calcium influx triggered by progesterone. Holding the Vm to
      values that maintained VDCCs in a deactivated (-71 mV) closed state inhibited the
      calcium influx induced by progesterone by approximately 40%. At this Vm, the
      acrosomal reaction induced by progesterone, but not by A23187, was inhibited.
      However, when the Vm was held at -15 mV (which maintains VDCCs in an inactivated
      closed state), the progesterone-induced calcium influx was stimulated.
      Furthermore, the progesterone and voltage-dependent calcium influxes were
      additive. These findings indicate that progesterone does not produce VDCC gating
      in human sperm.

PMID- 14662795
TI  - Selection of individual testicular tubules from biopsied testicular tissue with a
      stereomicroscope improves sperm retrieval rate.
AB  - The present study describes a new modification for testicular sperm extraction
      (TESE) with an intraoperative surgical loop, coupled with stereomicroscopic
      dissection in the laboratory, to identify sperm-containing tubules. The study
      included 116 consecutive patients with nonobstructive azoospermia (NOA)
      undergoing TESE and intracytoplasmic sperm injection. After dissection of
      testicular tissue under the stereomicroscope, patients were separated into 2
      groups according to tubular diameter. In the first group (n = 72), all tubules
      were of the same diameter. In the second group (n = 44), tubules with variable
      diameters could be identified. In such cases, 1-2 of the most distended and
      opaque seminiferous tubules were selected and minced alone, then examined for the
      presence of spermatozoa. The rest of the testicular tissue suspension was minced
      and examined separately. In 11 (25%) cases, retrieved spermatozoa were found in
      the isolated distended tubules only. In 21 (47.7%) cases, spermatozoa were found
      in both the isolated distended tubules and the rest of the specimen. In 2 cases,
      spermatozoa were found only in the whole sample, not in the isolated tubules. In
      the remaining 10 cases, spermatozoa were not found in either the whole sample or
      the isolated tubules. The sperm recovery rate in the isolated tubules was
      significantly higher than that of the rest of the specimen (72.7% vs 52%, chi(2)
      = 3.93, P <.05), and larger numbers of spermatozoa could be easily retrieved in a
      shorter period of time. In conclusion, the selection and isolation of the most
      dilated and opaque seminiferous tubules by using the surgical loop, coupled with
      laboratory stereoscopic dissection, improves sperm retrieval for men with NOA. It
      is possible that surgical-loops TESE coupled with stereomicroscope may offer
      superior sperm retrieval when compared with conventional TESE and may also offer
      reduced operative time when compared with microdissection TESE.

PMID- 14662796
TI  - Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig
      cells.
AB  - Presence of vascular endothelial growth factor (VEGF) is not only limited to
      cells directly involved in angiogenesis but has also been demonstrated in
      steroidogenic cells like testicular Leydig cells. Because Leydig cells are
      subjected to regulation by gonadotropic hormones and produce steroid hormones, we
      have investigated here the effects of human chorionic gonadotropin (hCG) or
      steroid hormones on VEGF expression in cultured mouse tumor Leydig cells (MA-10
      cells) and have then analyzed the underlying molecular mechanisms. Northern blot
      analysis and enzyme-linked immunosorbent assays revealed increases in VEGF mRNA
      and protein levels, respectively, over 3-20 hours in MA-10 cells after
      stimulation with hCG or 8-Br-cAMP. Although MA-10 cells lack the classical
      progesterone receptor, progesterone was able to stimulate VEGF expression.
      Promoter analyses and antibody supershift experiments suggested that the proximal
      region is able to constitutively bind the transcription factors Sp1 and Sp3.
      Mutations of 2 potential Sp1 binding sites in the proximal region showed the
      requirement of these motifs for stimulation of VEGF by hCG and 8-Br-cAMP. The
      distal cytosine-rich sequence interacts with so far-unidentified faster migrating
      factors. Following stimulation with hCG or 8-Br-cAMP, the binding of these
      proteins was increased in the complexes formed in the proximal and distal
      regions. VEGF expression in Leydig cells is regulated by gonadotropin via a cAMP
      dependent mechanism, and the transcription factors Sp1 and Sp3 appear to be
      involved in the activation of the promoter. Progesterone also appears to play a
      role in the regulation of VEGF, acting presumably via a nonconventional receptor
      that remains to be characterized yet.

PMID- 14662798
TI  - Chromosomal abnormalities and y chromosome microdeletions in infertile men with
      varicocele and idiopathic infertility of South Indian origin.
AB  - Various factors cause spermatogenesis arrest in men and, in a large number of
      cases, the underlying reason still remains unknown. Little attention is paid to
      determining the genetic defects of varicocele-related infertility. The objective
      of our present study was to investigate the chromosomal abnormalities and Y
      chromosome microdeletions in infertile men of South Indian origin with varicocele
      and idiopathic infertility. Metaphase chromosomes of 251 infertile men with
      varicocele and unexplained infertility were analyzed using Giemsa-Trypsin-Giemsa
      (GTG) banding and fluorescence in situ hybridization (FISH). The microdeletions
      in 6 genes and 18 sequence-tagged-sites (STS) in the Yq region were screened
      using polymerase chain reaction (PCR) techniques. Out of 251 infertile men, 57
      (22.7%) men were with varicocele, of which 8.77% were azoospermic, 26.31% were
      severely oligozoospermic, 21.05% were mildly oligozoospermic, and 43.85% were
      oligoasthenoteratozoospermic (OAT), and 194 (77.29%), with idiopathic
      infertility, of which 51% were azoospermic, 13.40% were severely oligozoospermic,
      19.07% were mildly oligozoospermic, and 16.4% were with OAT. Genetic defects were
      observed in 38 (15.13%) infertile individuals, including 14 (24.56%) men with
      varicocele and 24 (12.37%) men with idiopathic infertility. The frequencies of
      chromosomal defects in varicocele and idiopathic infertility were 19.3% and
      8.76%, respectively, whereas Y chromosome microdeletions were 5.26% and 3.60%,
      respectively. Overall rate of incidence of chromosomal anomalies and
      microdeletions in 251 infertile men were 11.5% and 3.98%, respectively,
      indicating a very significant higher association of genetic defects with
      varicocele than idiopathic male infertility. Our data also demonstrate that,
      among infertile men with varicocele, severely oligozoospermic and OAT men with
      varicocele have higher incidences of genetic defects than mildly oligozoospermic
      and azoospermic men.

PMID- 14662797
TI  - Identification of glutamate receptors and transporters in mouse and human sperm.
AB  - gamma-Aminobutyric acid (GABA) and glutamate (Glu) are considered as the
      predominant inhibitory and excitatory neurotransmitters in mammalian central
      nervous systems (CNS), respectively. The presence of the GABA system and
      metabotropic glutamate receptors in sperm prompted us to explore the existence of
      ionotropic glutamate receptors and glutamate transporters in sperm.
      Immunofluorescent analysis was used to investigate the existence and location of
      glutamate, glutamate receptor (NR2B), and glutamate transporter (GLT1) in mouse
      and human sperm. Our present results showed that NR2B was located in the midpiece
      of sperm, whereas GLT1 mainly existed in the head. Moreover, glutamate uptake
      activity was detected in mouse sperm and it could be blocked by dihydrokainic
      acid (DHK, GLT1-selective inhibitor) and DL-threo-beta-hydroxyaspartic acid (THA,
      nonselective inhibitor). In addition, reverse transcription-polymerase chain
      reaction technique and sequencing analysis revealed that glutamate transporters
      (GLT1 and EAAC1) and ionotropic glutamate receptors (NR1, NR2B, GluR6, and KA2)
      existed in mouse sperm as well as in human sperm. The present findings are the
      first direct evidence for the existence of ionotropic glutamate receptors and
      glutamate transporters in sperm. It also indicates that, in sperm, glutamate
      receptors and transporters might have functions other than neurotransmission.

PMID- 14662799
TI  - Zinc and metallothionein levels and expression of zinc transporters in androgen
      independent subline of LNCaP cells.
AB  - Zinc levels in the prostate have been reported to be associated with the
      development and progression of malignant prostate cells. To investigate the
      reason why the zinc content decreases during the progression of prostate cancer
      to an androgen-independent state, we compared the expression levels of
      metallothionein and zinc transporters between androgen-responsive LNCaP cells and
      its androgen-independent subline, AIDL cells. AIDL cells showed lower zinc levels
      than LNCaP cells and comparable levels of androgen receptor expression to LNCaP
      cells, consistent with some clinical aspects of androgen-independent prostatic
      cancer. AIDL cells exhibited a lower expression of zinc transporter 1 (ZnT1) and
      higher expression of ZnT3 than LNCaP cells. The content of metallothionein, which
      is a major zinc-binding protein, was significantly lower in AIDL cells than in
      LNCaP cells. Furthermore, the expression of ZnT3 mRNA was decreased by incubating
      LNCaP cells in medium containing hormone-stripped fetal calf serum and increased
      by addition of synthetic androgen R1881 to the medium, whereas the intracellular
      zinc levels were not affected under these conditions. These findings suggest that
      factors such as ZnT1 and metallothioneins other than ZnT3 are associated with the
      low intracellular zinc content in AIDL cells.

PMID- 14662800
TI  - OpenSDE: Row modeling applied to generic structured data entry.
AB  - Clinicians generally record medical narrative data, such as current complaints,
      physical examination, and progress notes, as free text in paper-based medical
      records. The medical narrative involves heterogeneous and detailed data that
      include the description of (multiple) occurrences of medical findings or symptoms
      that may progress over time. Structured, electronic recording of narrative data
      would facilitate the use of these data for research. The authors' OpenSDE
      application supports clinicians with the structured recording of narrative data
      in both research and care settings. Data entry is enabled using forms that are
      generated using domain-specific trees of medical concepts. For data storage, the
      authors have expanded the traditional row modeling methodology with additional
      columns that allow structured representation of medical narratives including
      descriptions of findings, multiple occurrences of findings, and the progression
      of findings over time.

PMID- 14662801
TI  - Do clinicians use online evidence to support patient care? A study of 55,000
      clinicians.
AB  - OBJECTIVES: To determine clinicians' (doctors', nurses', and allied health
      professionals') "actual" and "reported" use of a point-of-care online information
      retrieval system; and to make an assessment of the extent to which use is related
      to direct patient care by testing two hypotheses: hypothesis 1: clinicians use
      online evidence primarily to support clinical decisions relating to direct
      patient care; and hypothesis 2: clinicians use online evidence predominantly for
      research and continuing education. DESIGN: Web-log analysis of the Clinical
      Information Access Program (CIAP), an online, 24-hour, point-of-care information
      retrieval system available to 55,000 clinicians in public hospitals in New South
      Wales, Australia. A statewide mail survey of 5,511 clinicians. MEASUREMENTS:
      Rates of online evidence searching per 100 clinicians for the state and for the
      81 individual hospitals studied; reported use of CIAP by clinicians through a
      self-administered questionnaire; and correlations between evidence searches and
      patient admissions. RESULTS: Monthly rates of 48.5 "search sessions" per 100
      clinicians and 231.6 text hits to single-source databases per 100 clinicians (n =
      619,545); 63% of clinicians reported that they were aware of CIAP and 75% of
      those had used it. Eighty-eight percent of users reported CIAP had the potential
      to improve patient care and 41% reported direct experience of this. Clinicians'
      use of CIAP on each day of the week was highly positively correlated with patient
      admissions (r = 0.99, p < 0.001). This was also true for all ten randomly
      selected hospitals. CONCLUSION: Clinicians' online evidence use increases with
      patient admissions, supporting the hypothesis that clinicians' use of evidence is
      related to direct patient care. Patterns of evidence use and clinicians' self
      reports also support this hypothesis.

PMID- 14662802
TI  - Computerized physician order entry systems: is the pharmacist's role justified?

PMID- 14662803
TI  - e-Consent: The design and implementation of consumer consent mechanisms in an
      electronic environment.
AB  - The effective coordination of health care relies on communication of confidential
      information about consumers between different health and community care services.
      However, consumers must be able to give or withhold "e-Consent" to those who wish
      to access their electronic health information. There are several possible forms
      for e-Consent. In the general consent model, a patient provides blanket consent
      for access to his or her information by an organization for all future
      information requests. Conversely, general denial explicitly denies consent for
      information to be used in future circumstances, and in each new episode of care,
      a new consent would be needed to obtain information. In the general consent with
      specific denial model, a patient attaches specific exclusion conditions to his or
      her general approval to future accesses. In contrast, in the general denial with
      explicit consent model, a patient issues a blanket block on all future accesses
      but allows the inclusion of future use under specified conditions. There also are
      several alternative functions for an e-Consent system. Consent could be captured
      as a matter of legal record. E-Consent systems could be more active by prompting
      clinicians to indicate that they have noted consent conditions before they access
      a record. Finally, the record of patient consent could be fully active and used
      as a gatekeeper in a distributed information environment. There probably will
      need to be some form of data object that is associated with patient information.
      This e-Consent object (or e-Co) will contain the specific conditions under which
      the data to which it is attached can be retrieved. Given the complexity of
      clinical work and the substantial variation we can expect in an individual's
      desire to make his or her personal medical details available, it is unlikely a
      "one size fits all" approach to e-Consent will work. Consequently, with a well
      chosen consent design, it should be possible to balance the specific need for
      privacy of some of the population against the desire by others to err on the side
      of clinical safety, and clinicians desire to minimize the burden that an
      electronic consent mechanism would impose.

PMID- 14662806
TI  - Managing skin and soft tissue infections: expert panel recommendations on key
      decision points.

PMID- 14662807
TI  - NICE, the draft fertility guideline and dodging the big question.

PMID- 14662808
TI  - Use of assisted reproductive technology to reduce the risk of transmission of HIV
      in discordant couples wishing to have their own children where the male partner
      is seropositive with an undetectable viral load.

PMID- 14662809
TI  - The physician as an accessory in the parental project of HIV positive people.
AB  - The question of the moral acceptability of infertility treatment to HIV positive
      persons raises a number of interesting ethical points regarding the
      responsibility of the infertility specialist for the outcome of his or her
      actions. The analysis of the physician's responsibility is conducted within the
      framework of accomplice liability. The physician is a collaborator in the
      parental project of the principals--that is, the intentional parents. Both causal
      contribution and intention are considered as elements of complicity. It is
      concluded that a two per cent risk of vertical transmission when the woman is HIV
      positive is insufficient to blame the infertility specialist who helps her to
      conceive. Helping an infertile HIV positive infertile couple to have a child does
      not constitute reckless behaviour. When the couple is fertile, infertility
      treatment is directed at risk reduction and falls under the physician's
      obligation to act in the best interests of his patients.

PMID- 14662810
TI  - Should HIV discordant couples have access to assisted reproductive technologies?
AB  - In this paper we identify and evaluate arguments for and against offering
      assisted reproductive technologies (ART), specifically IVF, to HIV discordant
      couples (male partner HIV positive, female partner HIV negative). The idea of
      offering ART to HIV discordant couples generates concerns about safety and public
      health and raises questions such as: what is an acceptable level of risk to
      offspring and should couples who want this assistance be subject to selection
      criteria; should they undergo scrutiny about their suitability as parents when
      those who are able to conceive naturally face no such scrutiny and people with
      other illnesses are given access to ART? We conclude that offering ART to HIV
      discordant couples is likely to produce more benefit than harm and violates no
      ethical principles. Nevertheless, a decision to deny treatment need not
      constitute unjustified discrimination.

PMID- 14662811
TI  - When is physician assisted suicide or euthanasia acceptable?
AB  - OBJECTIVES: To discover what factors affect lay people's judgments of the
      acceptability of physician assisted suicide and euthanasia and how these factors
      interact. DESIGN: Participants rated the acceptability of either physician
      assisted suicide or euthanasia for 72 patient vignettes with a five factor design
      -that is, all combinations of patient's age (three levels); curability of illness
      (two levels); degree of suffering (two levels); patient's mental status (two
      levels), and extent of patient's requests for the procedure (three levels).
      PARTICIPANTS: Convenience sample of 66 young adults, 62 middle aged adults, and
      66 older adults living in western France. MAIN MEASUREMENTS: In accordance with
      the functional theory of cognition of N H Anderson, main effects, and
      interactions among patient factors and participants' characteristics were
      investigated by means of both graphs and ANOVA. RESULTS: Patient requests were
      the most potent determinant of acceptability. Euthanasia was generally less
      acceptable than physician assisted suicide, but this difference disappeared when
      requests were repetitive. As their own age increased, participants placed more
      weight on patient age as a criterion of acceptability. CONCLUSIONS: People's
      judgments concur with legislation to require a repetition of patients' requests
      for a life ending act. Younger people, who frequently are decision makers for
      elderly relatives, place less emphasis on patient's age itself than do older
      people.

PMID- 14662813
TI  - Stored human tissue: an ethical perspective on the fate of anonymous, archival
      material.
AB  - The furore over the retention of organs at postmortem examination, without
      adequate consent, has led to a reassessment of the justification for, and
      circumstances surrounding, the retention of any human material after postmortem
      examinations and operations. This brings into focus the large amount of human
      material stored in various archives and museums, much of which is not
      identifiable and was accumulated many years ago, under unknown circumstances.
      Such anonymous archival material could be disposed of, used for teaching, used
      for research, or remain in storage. We argue that there are no ethical grounds
      for disposing of the material, or for storing it in the absence of a teaching or
      research rationale. Nevertheless, with stringent safeguards, it can be used even
      in the absence of consent in research and teaching. Regulations are required to
      control the storage of all such human material, along the lines of regulations
      governing anatomy body bequests.

PMID- 14662812
TI  - Absent virtues: the poacher becomes gamekeeper.
AB  - Since its inception, bioethics' principled stance has been to argue against
      paternalism and elitism, and for an inclusive ethical perspective. But at least
      in North America, the growth of bioethics as a special area of applied ethics has
      created conflicts within the field itself. Those who, a generation earlier,
      argued against paternalism and for both professional and public accountability in
      medical decision making are now part of the decision making process. Too often,
      it is argued in this paper, their allegiance is to the employer, or to a view of
      medicine that is institutionally based. As a result, it is suggested by this
      review, medical ethicists have adopted the perspective that, in the early 1970s,
      they most criticised. The answer, it is argued here, is to revisit a
      lexicographical ordering of responsibility in bioethics, one that recognises
      professionals as individuals with responsibilities, as citizens with a public
      posture, and finally, as professionals involved in the process of medical
      decision making.

PMID- 14662814
TI  - The utilitarian argument for medical confidentiality: a pilot study of patients'
      views.
AB  - OBJECTIVES: To develop and pilot a questionnaire based assessment of the
      importance patients place on medical confidentiality, whether they support
      disclosure of confidential information to protect third parties, and whether they
      consider that this would impair full disclosure in medical consultations. DESIGN:
      Questionnaire administered to 30 consecutive patients attending a GP surgery.
      RESULTS: Overall patients valued confidentiality, felt that other patients might
      be deterred from seeking treatment if it were not guaranteed, but did not think
      that they would withhold information for this reason themselves. CONCLUSIONS:
      When presented with brief details of five clinical situations in which a breach
      of confidentiality might be considered, a clear majority of subjects believed
      that doctors should disclose information in two of the situations, but subjects
      were not confident that doctors would do so. In three situations, about half felt
      that disclosure was justified--these included the only scenario in which
      disclosure was clearly mandated by statute. There was little change in patients'
      general attitude to confidentiality after considering the scenarios. However, the
      views expressed were often inconsistent with responses to the clinical scenarios,
      suggesting that complex opinions were not accurately reflected in the responses.
      The format of the questionnaire has been amended, and the study will be repeated
      with other groups of patients.

PMID- 14662815
TI  - Priority setting in cardiac surgery: a survey of decision making and ethical
      issues.
AB  - OBJECTIVES: The aim of this study was to examine priority setting for coronary
      artery bypass surgery, and to provide an overview of decisions and rationales
      used in clinical practice. METHOD: Questionnaires were sent to all permanently
      employed cardiologists, cardiothoracic surgeons, and anaesthesiologists at nine
      Swedish hospitals performing adult cardiothoracic surgery. RESULTS: A total of
      208 physicians responded (a 44% return rate). There was considerable agreement
      concerning the criteria that should be used to set priorities for coronary artery
      bypass interventions (clusters of factors in synthesis). However, there was a
      lack of accord regarding the use of national guidelines for priority setting and
      risk indexes. CONCLUSIONS: Basic training and the strong support of ethical
      principles in priority setting are lacking. The respondents indicated a need for
      clearer guidelines and an open dialogue or discussion. The lack of generally
      acknowledged plans and guidelines for priority setting may result in unequal,
      conditional, and unfair treatment.

PMID- 14662816
TI  - Should patient consent be required to write a do not resuscitate order?
AB  - Consent ought to be required to withhold treatment that is in a patient's best
      interests to receive. Do not resuscitate (DNR) orders are examples of best
      interests assessments at the end of life. Such assessments represent value
      judgments that cannot be validly ascertained without patient input. If patient
      input results in that patient dissenting to the DNR order then individual
      physicians are not justified in overriding such dissent. To do so would give
      unjustifiable primacy to the values of the individual physician. Therefore
      patient consent is effectively required to write a DNR order. Patient dissent to
      a DNR order should trigger a fair process mechanism to resolve the dispute.

PMID- 14662817
TI  - The white coat ceremony: a contemporary medical ritual.

PMID- 14662818
TI  - White coat ceremonies--another commentary.

PMID- 14662820
TI  - Reporting of informed consent and ethics committee approval in genetics studies
      of stroke.

PMID- 14662821
TI  - Palliative care and cancer trials.

PMID- 14662822
TI  - Response to: Increasing use of DNR orders in the elderly worldwide: whose choice
      is it.

PMID- 14662824
TI  - In memoriam. Charles A. Janeway, Jr. February 5, 1943-April 12, 2003.

PMID- 14662825
TI  - In memoriam. D. Bernard Amos April 16, 1923-May 15, 2003.

PMID- 14662826
TI  - In memoriam. Robert A. Good May 21, 1922-June 13, 2003.

PMID- 14662827
TI  - The regulatory T cell family: distinct subsets and their interrelations.

PMID- 14662828
TI  - Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible
      inflammatory mediator with NF-kappa B suppressive properties.
AB  - Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene have been
      recently linked to three chronic autoinflammatory disorders. These observations
      point to an important role for CIAS1 in regulating inflammatory processes. We
      report that TNF-alpha and ligands recognized by multiple Toll-like receptors
      rapidly induce CIAS1 gene expression in primary human monocytes. Transfection of
      full-length CIAS1 or either of two shorter, naturally occurring isoforms
      dramatically inhibited TNF-alpha-induced activation of NF-kappaB reporter
      activity. Furthermore, CIAS1 suppressed TNF-alpha-induced nuclear translocation
      of endogenous p65. Transcriptional activity of exogenous NF-kappaB p65 was also
      blocked by CIAS1. The nucleotide-binding and leucine-rich repeat regions, but not
      the pyrin domain of CIAS1, are responsible for this inhibition. These data
      suggest CIAS1/cryopyrin may act as a key regulator of inflammation, induced to
      dampen NF-kappaB-dependent proinflammatory signals.

PMID- 14662829
TI  - Cutting edge: stimulation with the cognate self-antigen induces expression of the
      Ly49A receptor on self-reactive T cells which modulates their responsiveness.
AB  - NK cell self-tolerance is maintained by inhibitory receptors specific for MHC
      class I molecules. Inhibitory NK receptors are also expressed on memory CD8 T
      cells but their biological relevance on T cells is unclear. In this study, we
      describe the expression of the Ly49A receptor on a subset of autoreactive T cells
      which persist in mice double-transgenic for the lymphocytic choriomeningitis
      virus-derived peptide gp33 and a TCRalphabeta specific for the gp33. No Ly49A
      expressing cells are found in TCRalphabeta single-transgenic mice, indicating
      that the presence of the autoantigen is required for Ly49A induction. Direct
      evidence for an Ag-specific initiation of Ly49A expression has been obtained in
      vitro after stimulation of autoreactive TCRalphabeta T cells with the cognate
      self-Ag. This expression of Ly49A substantially reduces Ag-specific activation of
      autoreactive T cells. These findings thus suggest that autoantigen-specific
      induction of inhibitory NK cell receptors on T cells may contribute to peripheral
      self-tolerance.

PMID- 14662830
TI  - Cutting edge: CD4+ T cell help can be essential for primary CD8+ T cell responses
      in vivo.
AB  - Recent studies have shown that CD4(+) T cell help is required for the generation
      of memory CD8(+) T cells that can proliferate and differentiate into effector
      cells on Ag restimulation. The importance of help for primary CD8(+) T cell
      responses remains controversial. It has been suggested that help is not required
      for the initial proliferation and differentiation of CD8(+) T cells in vivo and
      that classical models of helper-dependent responses describe impaired secondary
      responses to Ag in vitro. We have measured primary CD8(+) T cell responses to
      peptide-pulsed dendritic cells in mice by cytokine ELISPOT and tetramer staining.
      No responses were detected in the absence of help, either when normal dendritic
      cells were injected into MHC II-deficient mice or when MHC II-deficient dendritic
      cells were injected into normal mice. Thus, the primary in vivo CD8(+) T cell
      response depends absolutely on help from CD4(+) T cells in our experimental
      system.

PMID- 14662831
TI  - Cutting edge: a potent adjuvant effect of ligand to receptor activator of NF
      kappa B gene for inducing antigen-specific CD8+ T cell response by DNA and viral
      vector vaccination.
AB  - The ligand to receptor activator of NF-kappaB (RANK-L)/RANK interaction has been
      implicated in CD40 ligand/CD40-independent T cell priming by dendritic cells. In
      this report, we show that the coadministration of the RANK-L gene with a
      Trypanosoma cruzi gene markedly enhances the induction of Trypanosoma Ag-specific
      CD8(+) T cells and improves the DNA vaccine efficacy. A similarly potent adjuvant
      effect of the RANK-L gene on the induction of Ag-specific CD8(+) T cells was also
      observed when recombinant influenza virus expressing murine malaria Ag was used
      as an immunogen. In contrast, the coadministration of the CD40L gene was not
      effective in these systems. Our results demonstrated, for the first time, the
      potent immunostimulatory effect of the RANK-L gene to improve the CD8(+) T cell
      mediated immunity against infectious agents.

PMID- 14662832
TI  - Deletion of naive CD8 T cells requires persistent antigen and is not programmed
      by an initial signal from the tolerogenic APC.
AB  - Activation of naive CD8 T cells in vivo requires the recognition of cognate
      peptide-MHC complexes on APCs. Depending upon the activation status of the APC,
      such recognition will promote either a vigorous immune response or T cell
      tolerance and deletion. Recent studies suggest that the initial signals provided
      by APCs are sufficient to program the proliferation of naive CD8 T cells and
      their differentiation into effector cells. In this study, we sought to determine
      whether an initial encounter with tolerogenic APCs was sufficient to program
      deletion of naive CD8 T cells. Surprisingly, we find that regardless of whether
      naive CD8 T cells were stimulated by activated or quiescent APCs, transfer of the
      activated T cells into an Ag-free host was sufficient to ensure survival. Thus,
      although the extent of clonal expansion and development of effector function is
      determined by the activation status of the stimulatory APC, peripheral clonal
      deletion requires persistent Ag and is not determined by the initial stimulatory
      event.

PMID- 14662833
TI  - Homing to nonlymphoid tissues is not necessary for effector Th1 cell
      differentiation.
AB  - The differentiation of naive T cells into effector Th1 cells is a complex process
      that may proceed in two steps, commitment and development. Initial TCR engagement
      and IFN-gamma signaling instruct the T cells to commit to the Th1 lineage, while
      subsequent IL-12 and potentially TCR signaling induces final differentiation into
      irreversible, Th1 effector cells. In agreement with a multistep process of Th1
      cell differentiation, effector Th1 cell generation requires repeated TCR and
      cytokine signaling, thus raising the possibility that commitment and
      differentiation processes may occur in two distinct anatomical sites, the
      lymphoid organ and the site of infection, respectively. We tested this
      possibility using a model of skin sensitization that permits a direct analysis of
      Ag-specific T cells both within lymphoid organs and at the site of sensitization.
      We show in this study that Ag presentation in the skin does not induce further
      differentiation of skin-infiltrating T cells that are highly divided and fully
      differentiated effector cells. Thus, effector Th1 cell differentiation is
      completed within lymphoid organs. In addition, we examined the heterogeneity of
      CD4 T cell responses in vivo through the analysis of the expression, by activated
      T cells, of different selectins, including P-selectin ligand and CD62L known to
      define separable effector populations. We delineated, in lymph nodes, at least
      five distinct subpopulations of activated CD4 T cells with different phenotypes
      and recirculation properties. Collectively, these results show that the lymphoid
      environment orchestrates T cell activation to generate a repertoire of effector T
      cells with a diversity of effector functions.

PMID- 14662834
TI  - Human dendritic cells express the IL-18R and are chemoattracted to IL-18.
AB  - IL-18 is secreted by a variety of cells such as epithelial cells, macrophages,
      and dendritic cells (DC), in particular, in areas of chronic inflammation. The
      effects of IL-18 are complex and not fully understood thus far. We sought to
      explore human DC as a new target for IL-18, since IL-18R expression has been
      described on myeloid cells such as macrophages and DC are likely to get in
      contact with IL-18 at sites of inflammatory reactions. We demonstrate the
      expression of the IL-18R on human DC in peripheral blood and epidermis, as well
      as monocyte-derived dendritic cells (MoDC). On MoDC, IL-18R expression is up
      regulated by IFN-gamma. IL-18 strongly up-regulated CD54 on MoDC, whereas the
      effect on MHC class II, CD83, and CD86 was only moderate and the expression of
      CD40 and CD80 was not affected. MoDC primed with IL-18 did not increase their
      capacity to stimulate the proliferation or IFN-gamma production of autologous T
      cells. However, IL-18 had a direct migratory effect on MoDC as indicated by
      induction of filamentous actin polymerization and migration in Boyden chamber
      experiments. In epidermal DC, IL-18 was also able to induce filamentous actin
      polymerization. Therefore, IL-18 might represent a novel mechanism to recruit DC
      to areas of inflammation, in particular under Th1 cytokine conditions where IFN
      gamma is increased such as psoriasis or inflammatory bowel diseases.

PMID- 14662835
TI  - B lymphocyte development in rabbit: progenitor B cells and waning of B
      lymphopoiesis.
AB  - In mammals that use gut-associated lymphoid tissues for expansion and somatic
      diversification of the B cell repertoire, B lymphopoiesis occurs early in
      ontogeny and does not appear to continue throughout life. In these species,
      including sheep, rabbit, and cattle, little is known about the pathway of B cell
      development and the time at which B lymphopoiesis wanes. We examined rabbit bone
      marrow by immunofluorescence with anti-CD79a and anti-mu and identified both proB
      and preB cells. The proB cells represent the vast majority of B-lineage cells in
      the bone marrow at birth and by incorporation of 5-bromo-2'-deoxyuridine, they
      appear to be a dynamic population. PreB cells reach maximum levels in the bone
      marrow at 3 wk of age, and B cells begin to accumulate at 7 wk of age. We cloned
      two VpreB and one lambda5 gene and demonstrated that they are expressed within B
      lineage cells in bone marrow. VpreB and lambda5 coimmunoprecipitated with the mu
      chain in lysates of 293T cells transfected with VpreB, lambda5, and mu,
      indicating that VpreB, lambda5, and mu-chains associate in a preB cell receptor
      like complex. By 16 wk of age, essentially no proB or preB cells are found in
      bone marrow and by PCR amplification, B cell recombination excision circles were
      reduced 200-fold. By 18 mo of age, B cell recombination excision circles were
      reduced 500- to 1000-fold. We suggest that B cell development in the rabbit
      occurs primarily through the classical, or ordered, pathway and show that B
      lymphopoiesis is reduced over 99% by 16 wk of age.

PMID- 14662836
TI  - Evidence for a ligand-mediated positive selection signal in differentiation to a
      mature B cell.
AB  - Positive selection is required for B cell differentiation, as indicated by the
      requirement for expression of the pre-B cell receptor (pre-BCR) and the BCR at
      the pre-B and immature B cell stages, respectively. Positive selection mediated
      by a tonic signal from these receptors is sufficient to drive B cell
      differentiation beyond the pre-B and immature B cell stages, but it is unclear
      whether additional positive selection signals are required for differentiation to
      a mature B-2 cell. We have identified a population of Ig transgenic B cells that
      differentiatively arrest at a transitional B cell stage in the spleen. They
      exhibit no evidence of Ag encounter or negative selection and can differentiate
      to mature B-2 cells in vivo upon weak BCR stimulation or adoptive transfer to
      irradiated hosts. These data are consistent with a requirement for a ligand
      mediated BCR signal for differentiation to a mature B-2 cell.

PMID- 14662837
TI  - Proinflammatory actions of thromboxane receptors to enhance cellular immune
      responses.
AB  - Metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway generates a
      family of prostanoid mediators. Nonsteroidal anti-inflammatory drugs (NSAIDs) act
      by inhibiting COX, thereby reducing prostanoid synthesis. The efficacy of these
      agents in reducing inflammation suggests a dominant proinflammatory role for the
      COX pathway. However, the actions of COX metabolites are complex, and certain
      prostanoids, such as PGE(2), in some circumstances actually inhibit immune and
      inflammatory responses. In these studies, we examine the hypothesis that anti
      inflammatory actions of NSAIDs may be due, in part, to inhibition of thromboxane
      A(2) synthesis. To study the immunoregulatory actions of thromboxane A(2), we
      used mice with a targeted disruption of the gene encoding the thromboxane
      prostanoid (TP) receptor. Both mitogen-induced responses and cellular responses
      to alloantigen were substantially reduced in TP(-/-) spleen cells. Similar
      attenuation was observed with pharmacological inhibition of TP signaling in wild
      type splenocytes, suggesting that reduced responsiveness was not due to subtle
      developmental abnormalities in the TP-deficient mice. The absence of TP receptors
      reduced immune-mediated tissue injury following cardiac transplant rejection, an
      in vivo model of intense inflammation. Taken together, these findings show that
      thromboxane augments cellular immune responses and inflammatory tissue injury.
      Specific inhibition of the TP receptor may provide a more precise approach to
      limit inflammation without some of the untoward effects associated with NSAIDs.

PMID- 14662838
TI  - Effective genetic vaccination with a widely shared endogenous retroviral tumor
      antigen requires CD40 stimulation during tumor rejection phase.
AB  - Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and
      humans. As these Ags are preferentially expressed by neoplastic tissues, they
      might represent an ideal target for active immunization by genetic vaccination.
      However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two
      products of the env gene of an endogenous murine leukemia virus, elicited a weak
      Ag-specific T lymphocyte response and resulted in partial protection from
      challenge with mouse tumors possessing these Ags. Depletion experiments showed
      that CD8(+), but not CD4(+), T lymphocytes were crucial for the antitumor
      activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb
      increased the therapeutic potential of genetic vaccination, but only when given
      during the tumor rejection phase and not at the time of immunization. This effect
      correlated with a dramatic increase in the number of ERV-specific CD8(+) T
      lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to
      enhance the CD8(+) T cell-dependent response in tumor-bearing hosts, suggesting
      that sustaining tumor-specific T lymphocyte survival in subjects undergoing
      vaccination might be a key event in the successful vaccination with weak tumor
      Ags.

PMID- 14662839
TI  - Newly activated T cells promote maturation of bystander dendritic cells but not
      IL-12 production.
AB  - The activation of dendritic cells (DC) leads to increased costimulatory activity
      (termed DC maturation) and, in some instances, production of immunomodulatory
      cytokines such as IL-12. Both innate and T cell-derived signals can promote DC
      activation but it is unclear to what extent the two classes of stimuli are
      interchangeable or regulate distinct aspects of DC function. In this study, we
      show that signals from newly activated CD4(+) T cells cannot initiate IL-12
      synthesis although they can amplify secretion of bioactive IL-12 p70 by DC
      exposed to an appropriate innate stimulus. This occurs exclusively in cis and
      does not influence IL-12 synthesis by bystander DC that do not present Ag. In
      marked contrast, signals from newly activated CD4(+) T cells can induce an
      increase in DC costimulatory activity in the absence of any innate priming. This
      occurs both in cis and in trans, affecting all DC in the microenvironment,
      including those that do not bear specific Ag. Consistent with the latter, we show
      that newly activated CD4(+) T cells in vivo can deliver "help" in trans,
      effectively lowering the number of MHC/peptide complexes required for
      proliferation of third-party naive CD4(+) T cells recognizing Ag on bystander DC.
      These results demonstrate that DC maturation and cytokine production are
      regulated distinctly by innate stimuli vs signals from CD4(+) T cells and reveal
      a process of trans activation of DC without secretion of polarizing cytokines
      that takes place during T cell priming and may be involved in amplifying immune
      responses.

PMID- 14662840
TI  - Phosphodiesterase 7A-deficient mice have functional T cells.
AB  - Phosphodiesterases (PDEs) are enzymes which hydrolyze the cyclic nucleotide
      second messengers, cAMP and cGMP. In leukocytes, PDEs are responsible for
      depletion of cAMP which broadly suppresses cell functions and cellular responses
      to many activation stimuli. PDE7A has been proposed to be essential for T
      lymphocyte activation based on its induction during cell activation and the
      suppression of proliferation and IL-2 production observed following inhibition of
      PDE7A expression using a PDE7A antisense oligonucleotide. These observations have
      led to the suggestion that selective PDE7 inhibitors could be useful in the
      treatment of T cell-mediated autoimmune diseases. In the present report, we have
      used targeted gene disruption to examine the role PDE7A plays in T cell
      activation. In our studies, PDE7A knockout mice (PDE7A(-/-)) showed no
      deficiencies in T cell proliferation or Th1- and Th2-cytokine production driven
      by CD3 and CD28 costimulation. Unexpectedly, the Ab response to the T cell
      dependent Ag, keyhole limpet hemocyanin, in the PDE7A(-/-) mice was found to be
      significantly elevated. The results from our studies strongly support the notion
      that PDE7A is not essential for T cell activation.

PMID- 14662841
TI  - Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209)
      intermediate cell and impair differentiation into dendritic cells.
AB  - Recruitment of monocytes into tissues and their differentiation into macrophages
      or dendritic cells (DCs) depend on the microenvironment of the inflammatory site.
      Although many factors affecting this process have been identified, the
      intracellular signaling pathways implicated are poorly understood. We found that
      cyclic nucleotides regulate certain steps of monocyte differentiation into DCs.
      Increased levels of the cyclic nucleotides, cAMP or cGMP, inhibit differentiation
      of CD14(+)/CD1a(low) monocytes into CD14(-)/CD1a(high) DCs. However, DC-specific
      ICAM-3-grabbing nonintegrin (CD209) up-regulation was not affected by cyclic
      nucleotides, indicating that DC development was not blocked at the monocyte
      stage. Interestingly, Ag-presenting function was increased by cyclic nucleotides,
      as measured by the higher expression of MHC class II, CD86, and an increased
      ability to stimulate CD4(+) T cell proliferation in allogeneic MLRs. Although
      cyclic nucleotides do not completely block DC differentiation, they do block the
      ability of DCs to be induced to mature by LPS. Treatment during DC
      differentiation with either cAMP or cGMP analogues hampered LPS-induced
      expression of CD83, DC-LAMP, and CCR7 and the ability of DCs to migrate toward
      CCL19/macrophage-inflammatory protein 3beta. Interestingly, the induction of a
      CD16(+) subpopulation of cells was also observed. Thus, signals causing an
      increase in either cAMP or cGMP levels during monocyte recruitment to
      inflammatory sites may restrain the activation of acquired immunity by blocking
      DC development and migration to lymph nodes. At the same time, these signals
      promote development of an active intermediate cell type having properties between
      those of macrophages and DCs, which might contribute to the innate immune
      response in the periphery.

PMID- 14662842
TI  - IL-15 and cognate antigen successfully expand de novo-induced human antigen
      specific regulatory CD4+ T cells that require antigen-specific activation for
      suppression.
AB  - An important prerequisite in using regulatory T cells for immunotherapy is their
      ex vivo expansion without loss of suppressor function. Human anergic regulatory T
      cells are expandable by Ag-specific stimulation in the presence of IL-2. IL-15,
      like IL-2, is a T cell growth factor that, in contrast to IL-2, stimulates
      survival of T cells. In this study, we examined whether IL-15 could be exploited
      as a superior growth factor of human CD4(+) anergic regulatory T cells that were
      generated by costimulation blockade. Next, IL-15, as compared with IL-2, was
      investigated with respect to expansion and function of these regulatory T cells.
      Optimal expansion required cognate allogeneic stimulation in the presence of
      exogenous IL-15. IL-15 resulted in enhanced survival that was paralleled by an
      increased number of Bcl-2-expressing cells. Moreover, IL-15 induced a distinct
      type of anergy characterized by hyperreactivity to IL-15, resulting in improved
      expansion. This is likely attributed to increased propensity of these cells to up
      regulate both alpha- and gamma-chains of the IL-2 and IL-15 receptor. Notably, IL
      15-expanded regulatory CD4(+) T cells suppressed both naive and memory T cells in
      a superior way. Immunosuppression required alloantigen-specific stimulation and
      appeared gamma-irradiation resistant and independent of IL-10, TGFbeta, or CTLA-4
      interactions. These regulatory T cells were stable suppressors, mediating
      bystander suppression upon TCR stimulation, but leaving recall responses
      unaffected in the absence of cognate Ag. Finally, human naturally occurring
      regulatory CD4(+)CD25(+) T cells appeared important in generating regulatory T
      cells by costimulation blockade. In conclusion, IL-15-expanded, de novo-induced
      human anergic regulatory CD4(+) T cells are of interest in Ag-specific
      immunotherapy.

PMID- 14662843
TI  - Genetic complementation in female (BXSB x NZW)F2 mice.
AB  - F(1) hybrids among New Zealand Black (NZB), New Zealand White (NZW), and BXSB
      lupus-prone strains develop accelerated autoimmunity in both sexes regardless of
      the specific combination. To identify BXSB susceptibility loci in the absence of
      the Y chromosome accelerator of autoimmunity (Yaa) and to study the genetics of
      this complementation, genome-wide quantitative trait locus (QTL) mapping was
      performed on female (BXSB x NZW)F(2) mice. Six QTL were identified on chromosomes
      1, 4, 5, 6, 7, and 17. Survival mapped to chromosomes 5 and 17, anti-chromatin Ab
      to chromosomes 4 and 17, glomerulonephritis to chromosomes 6 and 17, and
      splenomegaly to chromosomes 1, 7, and 17. QTL on chromosomes 4 and 6 were new and
      designated as Lxw1 and -2, respectively. Two non-MHC QTL (chromosomes 1 and 4)
      were inherited from the BXSB and the rest were NZW-derived, including two similar
      to previously defined loci. Only two of 11 previously defined non-MHC BXSB QTL
      using male (Yaa(+)) crosses were implicated, suggesting that some male-defined
      BXSB QTL may require coexpression of the Yaa. Findings from this and other
      studies indicate that BXSB and NZB backgrounds contribute completely different
      sets of genes to complement NZW mice. Identification of susceptibility genes and
      complementing genes in several lupus-prone strain combinations will be important
      for defining the epistatic effects and background influences on the heterogeneous
      genetic factors responsible for lupus induction.

PMID- 14662844
TI  - Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and
      invasiveness.
AB  - In this study, we show that distinct compartmentalization patterns of the IL-1
      molecules (IL-1alpha and IL-1beta), in the milieu of tumor cells that produce
      them, differentially affect the malignant process. Active forms of IL-1, namely
      precursor IL-1alpha (pIL-1alpha), mature IL-1beta (mIL-1beta), and mIL-1beta
      fused to a signal sequence (ssIL-1beta), were transfected into an established
      fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed.
      Cell lines transfected with pIL-1alpha, which expresses IL-1alpha on the
      membrane, fail to develop local tumors and activate antitumor effector
      mechanisms, such as CTLs, NK cells, and high levels of IFN-gamma production.
      Cells transfected with secretable IL-1beta (mIL-1beta and ssIL-1beta) were more
      aggressive than wild-type and mock-transfected tumor cells; ssIL-1beta
      transfectants even exhibited metastatic tumors in the lungs of mice after i.v.
      inoculation (experimental metastasis). In IL-1beta tumors, increased vascularity
      patterns were observed. No detectable antitumor effector mechanisms were observed
      in spleens of mice injected with IL-1beta transfectants, mock-transfected or wild
      type fibrosarcoma cells. Moreover, in spleens of mice injected with IL-1beta
      transfectants, suppression of polyclonal mitogenic responses (proliferation, IFN
      gamma and IL-2 production) to Con A was observed, suggesting the development of
      general anergy. Histologically, infiltrating mononuclear cells penetrating the
      tumor were seen at pIL-1alpha tumor sites, whereas in mIL-1beta and ssIL-1beta
      tumor sites such infiltrating cells do not penetrate inside the tumor. This is,
      to our knowledge, the first report on differential, nonredundant, in vivo effects
      of IL-1alpha and IL-1beta in malignant processes; IL-1alpha reduces
      tumorigenicity by inducing antitumor immunity, whereas IL-1beta promotes
      invasiveness, including tumor angiogenesis, and also induces immune suppression
      in the host.

PMID- 14662845
TI  - EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent
      antitumor responses in a lung cancer model.
AB  - The antitumor efficacy of EBV-induced molecule 1 ligand CC chemokine (ELC/CCL19)
      was evaluated in a murine lung cancer model. The ability of ELC/CCL19 to
      chemoattract both dendritic cells and T lymphocytes formed the rationale for this
      study. Compared with diluent-treated tumor-bearing mice, intratumoral injection
      of recombinant ELC/CCL19 led to significant systemic reduction in tumor volumes
      (p < 0.01). ELC/CCL19-treated mice exhibited an increased influx of CD4 and CD8 T
      cell subsets as well as dendritic cells at the tumor sites. These cell
      infiltrates were accompanied by increases in IFN-gamma, MIG/CXCL9, IP-10/CXCL10,
      GM-CSF, and IL-12 but a concomitant decrease in the immunosuppressive molecules
      PGE(2) and TGFbeta. Transfer of T lymphocytes from ELC/CCL19 treated tumor
      bearing mice conferred the antitumor therapeutic efficacy of ELC/CCL19 to naive
      mice. ELC/CCL19 treated tumor-bearing mice showed enhanced frequency of tumor
      specific T lymphocytes secreting IFN-gamma. In vivo depletion of IFN-gamma,
      MIG/CXCL9, or IP-10/CXCL10 significantly reduced the antitumor efficacy of
      ELC/CCL19. These findings provide a strong rationale for further evaluation of
      ELC/CCL19 in tumor immunity and its use in cancer immunotherapy.

PMID- 14662846
TI  - Mouse strain differences in plasmacytoid dendritic cell frequency and function
      revealed by a novel monoclonal antibody.
AB  - We report in this study the generation of a novel rat mAb that recognizes mouse
      plasmacytoid dendritic cells (pDC). This Ab, named 120G8, stains a small subset
      of CD11c(low) spleen cell with high specificity. This population produces high
      amounts of IFN-alpha upon in vitro viral stimulation. Both ex vivo- and in vitro
      derived 120G8(+) cells display a phenotype identical with that of the previously
      described mouse pDC (B220(high)Ly6C(high)Gr1(low)CD11b(-)CD11c(low)). Mice
      treated with 120G8 mAb are depleted of B220(high)Ly6C(high)CD11c(low) cells and
      have a much-reduced ability to produce IFN-alpha in response to in vivo CpG
      stimulation. The mAb 120G8 stains all and only B220(high)Ly6C(high)CD11c(low) pDC
      in all lymphoid organs. Immunohistochemical studies performed with this mAb
      indicate that pDC are located in the T cell area of spleen, lymph nodes, and
      Peyer's patches. Although the Ag recognized by 120G8 is not yet known, we show
      that its expression is up-regulated by type I IFN on B cells and DC. Using this
      mAb in immunofluorescence studies demonstrates strain- and organ-specific
      differences in the frequency of pDC and other DC subsets. 129Sv mice have a much
      higher frequency of pDC, together with a lower frequency of conventional
      CD8alpha(+)CD11c(high) DC, compared with C57BL/6 mice, both in spleen and blood.
      The higher ability of 129Sv mice to produce IFN-alpha in vivo is related to a
      higher number of pDC, but also to a higher ability of pDC from 129Sv mice to
      produce IFN-alpha in vitro in response to viral stimulation.

PMID- 14662847
TI  - CD40-induced aggregation of MHC class II and CD80 on the cell surface leads to an
      early enhancement in antigen presentation.
AB  - Ligation of CD40 on B cells increases their ability to present Ag and to activate
      MHC class II (MHC-II)-restricted T cells. How this occurs is not entirely clear.
      In this study we demonstrate that CD40 ligation on Ag-presenting B cells (APC)
      for a short period between 30 min and 3 h has a rapid, augmenting effect on the
      ability of a B cell line and normal B cells to activate T cells. This is not due
      to alterations in Ag processing or to an increase in surface expression of CD80,
      CD86, ICAM-1, or MHC-II. This effect is particularly evident with naive, resting
      T lymphocytes and appears to be more pronounced under limiting Ag concentrations.
      Shortly after CD40 ligation on a B cell line, MHC-II and CD80 progressively
      accumulated in cholesterol-enriched microdomains on the cell surface, which
      correlated with an initial enhancement in their Ag presentation ability.
      Moreover, CD40 ligation induced a second, late, more sustained enhancement of Ag
      presentation, which correlates with a significant increase in CD80 expression by
      APC. Thus, CD40 signaling enhances the efficiency with which APC activate T cells
      by at least two related, but distinct, mechanisms: an early stage characterized
      by aggregation of MHC-II and CD80 clusters, and a late stage in which a
      significant increase in CD80 expression is observed. These results raise the
      possibility that one important role of CD40 is to contribute to the formation of
      the immunological synapse on the APC side.

PMID- 14662848
TI  - The interaction of gamma delta T cells with activated macrophages is a property
      of the V gamma 1 subset.
AB  - Immunoregulation is an emerging paradigm of gammadelta T cell function. The
      mechanisms by which gammadelta T cells mediate this function, however, are not
      clear. Studies have identified a direct role for gammadelta T cells in resolving
      the host immune response to infection, by eliminating populations of activated
      macrophages. The aim of this study was to identify macrophage-reactive gammadelta
      T cells and establish the requirements/outcomes of macrophage-gammadelta T cell
      interactions during the immune response to the intracellular bacterium, Listeria
      monocytogenes (Lm). Using a macrophage-T cell coculture system in which
      peritoneal macrophages from naive or Lm-infected TCRdelta(-/-) mice were
      incubated with splenocytes from naive and Lm-infected alphabeta/gammadelta T cell
      deficient and wild-type mice, the ability to bind macrophages was shown to be
      restricted to gammadelta T cells and the GV5S1 (Vgamma1) subset of gammadelta T
      cells. Macrophage adherence resulted in a 4- to 10-fold enrichment of Vgamma1(+)
      T cells. Enrichment of Vgamma1 T cells was dependent upon the activation status
      of macrophages, but independent of the activation status of gammadelta T cells.
      Vgamma1 T cells were cytotoxic for activated macrophages with both the binding to
      and killing of macrophages being TCR dependent because anti-TCRgammadelta Abs
      inhibited both Vgamma1 binding and killing activities. These studies establish
      the identity of macrophage cytotoxic gammadelta T cells, the conditions under
      which this interaction occurs, and the outcome of this interaction. These
      findings are concordant with the involvement of Vgamma1 T cells in macrophage
      homeostasis during the resolution of pathogen-mediated immune responses.

PMID- 14662850
TI  - Alloreactive CD4 T cell activation in vivo: an autonomous function of the
      indirect pathway of alloantigen presentation.
AB  - Activation of alloreactive CD4 T cells occurs via the direct and indirect
      pathways of alloantigen presentation. A novel TCR/alloantigen transgenic system
      was designed that permitted in vivo visualization of CD4 T cell priming through
      these pathways. When both pathways of alloantigen presentation were intact, CD4 T
      cell activation in response to cardiac allografts was rapid and systemic by day 4
      after transplantation, in contrast to that seen in response to skin allografts,
      which was delayed until 10-12 days after transplantation. Despite this systemic
      CD4 T cell activation in response to cardiac allografts, there was a paucity of
      activated graft-infiltrating CD4 T cells at 4 days posttransplantation. This
      finding suggests that the initial priming of alloimmune CD4 T cell responses
      occurs within draining lymphoid organs. Furthermore, alloantigens derived from
      cardiac allografts failed to promote thymic negative selection of developing
      thymocytes expressing the alloreactive TCR clonotype. In the absence of a
      functional direct pathway, the kinetics of activation, anatomic localization, and
      effector function of alloreactive CD4 T cells remained unchanged. Overall, the
      present study defines the anatomic and temporal characteristics of CD4 T cell
      alloimmune responses and demonstrates that CD4 T cell priming via the indirect
      pathway proceeds optimally in the absence of the direct pathway of alloantigen
      presentation.

PMID- 14662849
TI  - The selection of marginal zone B cells differs from that of B-1a cells.
AB  - Transgenic (Tg) L2 mice expressing high levels of the lambda2 (315) L chain
      contain only B cell populations involved in the first line of defense, i.e., B-1
      and marginal zone (MZ) B cells. The strongly oligoclonal IgH chain repertoire of
      Tg B-1a cells in such mice was attributed to strong positive selection by
      autoantigens. In this study, we show that the MZ B cells of L2 mice correspond
      very closely to MZ B cells of normal mice, as revealed by surface marker
      expression and gene expression profiling. We demonstrate that the IgH chain
      repertoire of these Tg MZ B cells is extremely heterogeneous. This is in sharp
      contrast to the oligoclonality found in B-1a cells of the same mice, which was
      attributed to strong positive selection mediated by autoantigens. Therefore, the
      strong positive selection of the IgH chain repertoire in L2 mice is B-1a
      specific. Thus, our data demonstrate that despite common functional properties,
      MZ B and B-1a cells exhibit striking differences in their selection and/or
      maintenance requirements.

PMID- 14662851
TI  - The male minor transplantation antigen preferentially activates recipient CD4+ T
      cells through the indirect presentation pathway in vivo.
AB  - To evaluate the priming and trafficking of male Ag-reactive CD4(+) T cells in
      vivo, we developed an adoptive transfer model, using Marilyn (Mar) TCR transgenic
      T cells that are specific for the H-Y minor transplantation Ag plus I-A(b). By
      manipulating donor and recipient strain combinations, we permitted the Mar CD4(+)
      T cells to respond to the H-Y Ag after processing and presentation by recipient
      APCs (indirect pathway), or to the male Ag as expressed on donor APCs (direct
      pathway). Mar CD4(+) T cells responding through the indirect pathway specifically
      proliferated and expressed activation markers between days 2 and 4
      posttransplant, migrated to the graft 2-3 days before cessation of graft
      heartbeat, and were detected in close proximity to transplant-infiltrating
      recipient APCs. Intriguingly, adoptively transferred Mar T cells did not respond
      to male heart or skin grafts placed onto syngeneic MHC class II-deficient female
      recipients, demonstrating that activation of Mar T cell preferentially occurs
      through cognate interactions with processed male Ag expressed on recipient APCs.
      The data highlight the potency of indirect processing and presentation pathways
      in vivo and underscore the importance of indirectly primed CD4(+) T cells as
      relevant participants in both the priming and effector phases of acute graft
      rejection.

PMID- 14662852
TI  - Neuronal repellent Slit2 inhibits dendritic cell migration and the development of
      immune responses.
AB  - One of the essential functions of dendritic cells is to take up Ags in peripheral
      tissues and migrate into secondary lymphoid organs to present Ags to lymphocytes
      for the induction of immune responses. Although many studies have demonstrated
      that the migration of dendritic cells is closely associated with the development
      of immune responses, little is known about factors that inhibit dendritic cell
      migration and control the extent of immune responses to Ag stimulation. We show
      that Slit2, a neuronal repellent factor, is up-regulated in the skin by allergen
      sensitization and down-regulates the migration of Langerhans cells. The effect is
      mediated by direct interaction of Slit2 with cells that express a Slit-specific
      receptor, Robo1. Slit2-mediated inhibition of Langerhans cell migration results
      in suppression of contact hypersensitivity responses. These findings provide
      insights into a novel mechanism by which Slit2 functions as an anti-inflammatory
      factor for the initiation of immune responses.

PMID- 14662853
TI  - CD43 modulates severity and onset of experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple
      sclerosis characterized by infiltration of activated CD4(+) T lymphocytes into
      tissues of the CNS. This study investigated the role of CD43 in the induction and
      progression of EAE. Results demonstrate that CD43-deficient mice have reduced and
      delayed clinical and histological disease severity relative to CD43(+/+) mice.
      This reduction was characterized by decreased CD4(+) T cell infiltration of the
      CNS of CD43(-/-) mice but similar numbers of Ag-specific T cells in the
      periphery, suggesting a defect in T cell trafficking to the CNS. The absence of
      CD43 also affected cytokine production, as myelin oligodendrocyte glycoprotein
      (MOG) 35-55-specific CD43(-/-) CD4(+) T cells exhibited reduced IFN-gamma and
      increased IL-4 production. CD43(-/-) CD4(+) MOG-primed T cells exhibited reduced
      encephalitogenicity relative to CD43(+/+) cells upon adoptive transfer into naive
      recipients. These results suggest a role for CD43 in the differentiation and
      migration of MOG(35-55)-specific T cells in EAE, and identify it as a potential
      target for therapeutic intervention.

PMID- 14662854
TI  - Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells.
AB  - Peripheral T lymphocytes undergo activation by antigenic stimulation and function
      in hypoxic areas of inflammation. We demonstrated in CD3-positive human T cells
      accumulating in inflammatory tissue expression of the hypoxia-inducible factor
      1alpha (HIF-1alpha), indicating a role of hypoxia-mediated signals in regulation
      of T cell function. Surprisingly, accumulation of HIF-1alpha in human T cells
      required not only hypoxia but also TCR/CD3-mediated activation. Moreover, hypoxia
      repressed activation-induced cell death (AICD) by TCR/CD3 stimulation, resulting
      in an increased survival of the cells. Microarray analysis suggested the
      involvement of HIF-1 target gene product adrenomedullin (AM) in this process.
      Indeed, AM receptor antagonist abrogated hypoxia-mediated repression of AICD.
      Moreover, synthetic AM peptides repressed AICD even in normoxia. Taken together,
      we propose that hypoxia is a critical determinant of survival of the activated T
      cells via the HIF-1alpha-AM cascade, defining a previously unknown mode of
      regulation of peripheral immunity.

PMID- 14662855
TI  - CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast
      formation.
AB  - By homology to triggering receptor expressed by myeloid cells-2, we screened the
      mouse expressed sequence tag database and isolated a new single Ig domain
      receptor, which we have expressed and characterized. The receptor is most similar
      in sequence to the human CMRF-35 receptor, and thus we have named it CMRF-35-like
      molecule (CLM)-1. By screening the mouse genome, we determined that CLM-1 was
      part of a multigene family located on a small segment of mouse chromosome 11.
      Each contains a single Ig domain, and they are expressed mainly in cells of the
      myeloid lineage. CLM-1 contains multiple cytoplasmic tyrosine residues, including
      two that lie in consensus immunoreceptor tyrosine-based inhibitory motifs, and we
      demonstrate that CLM-1 can associate with Src-homology 2 containing phosphatase
      1. Expression of CLM-1 mRNA is down-regulated by treatment with receptor
      activator of NF-kappaB ligand (RANKL), a cytokine that drives osteoclast
      formation. Furthermore, expression of CLM-1 in the osteoclastogenic cell line RAW
      (RAW.CLM-1) prevents osteoclastogenesis induced by RANKL and TGF-beta. RAW.CLM-1
      cells fail to multinucleate and do not up-regulate calcitonin receptor, but they
      express tartrate-resistant acid phosphatase, cathepsin K, and beta(3) integrin,
      suggesting that osteoclastogenesis is blocked at a late-intermediate stage. Thus,
      we define a new family of myeloid receptors, and demonstrate that the first
      member of this family, CLM-1, is an inhibitory receptor, able to block
      osteoclastogenesis.

PMID- 14662856
TI  - Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by
      inducing IL-10-producing CD4+ T cells.
AB  - Inflammation plays an important role in ischemic stroke and in humans IL-10 may
      have a beneficial effect in stroke. We mucosally administered myelin
      oligodendrocyte glycoprotein (MOG) 35-55 peptide to C57BL/6 mice before middle
      cerebral artery occlusion (MCAO) to induce an anti-inflammatory T cell response
      directed at CNS myelin. Nasal and oral administration of MOG(35-55) peptide
      decreased ischemic infarct size at 24 and 72 h after MCAO surgery. Nasal MOG(35
      55) peptide was most efficacious and reduced infarct size by 70% at 24 h and by
      50% at 72 h (p <or= 0.0001 vs control) and also improved behavior score.
      Immunohistochemistry demonstrated increased IL-10 and reduced IFN-gamma in the
      area surrounding the ischemic infarct following nasal treatment. Nasal MOG did
      not reduce infarct size in IL-10-deficient mice. Adoptive transfer of CD4(+) T
      cells to untreated mice from nasally tolerized mice before MCAO surgery decreased
      stroke size (p < 0.001 vs control), whereas, CD4(+) T cells from nasally
      tolerized IL-10-deficient mice had no effect. Our results demonstrate that IL-10
      secreting CD4(+) T cells induced by nasal MOG reduce injury following stroke. In
      addition, we observed a dramatic reduction of CD11b(+) cells in nasal MOG-treated
      animals. CD11b(+) cells may contribute to secondary infarct expansion by
      enhancing NO synthesis that may be reduced by elevated IL-10 levels. Modulation
      of cerebral inflammation by nasal vaccination with myelin Ags that increase IL-10
      in the brain may improve outcome after stroke and enhance mechanisms of recovery.

PMID- 14662857
TI  - Reduced switching in SCID B cells is associated with altered somatic mutation of
      recombined S regions.
AB  - Deoxyribonucleic acid double-stranded breaks act as intermediates in Ig V(D)J
      recombination and probably perform a similar function in class switch
      recombination between IgH C genes. In SCID mice, V(D)J recombination is blocked
      because the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) protein is
      defective. We show in this study that switching to all isotypes examined was
      detectable when the SCID mutation was introduced into anti-hen egg lysozyme
      transgenic B cells capable of undergoing class switch recombination, but
      switching was significantly reduced in comparison with control B cells of the
      same specificity lacking the RAG1 gene. Thus, DNA-PKcs is involved in switching
      to all isotypes, but plays a lesser role in the switching process than it does in
      V(D)J-coding joint formation. The higher level of switching observed by us in
      SCID B cells compared with that observed by others in DNA-PKcs(null) cells raises
      the possibility that kinase-deficient DNA-PKcs can function in switching. Point
      mutation of G:C base pairs with cytidines on the sense strand was greatly reduced
      in recombined switch regions from SCID cells compared with control RAG1(-/-) B
      cells. The preferential loss of sense strand cytidine mutations from hybrid S
      regions in SCID cells suggests the possibility that nicks might form in S regions
      of activated B cells on the template strand independently of activation-induced
      cytidine deaminase and are converted to double-strand breaks when activation
      induced cytidine deaminase deaminates the non-template strand.

PMID- 14662858
TI  - Expression and characterization of the C345C/NTR domains of complement components
      C3 and C5.
AB  - Complement components C3, C4, and C5 are members of the thioester-containing
      alpha-macroglobulin protein superfamily. Within this superfamily, a unique
      feature of the complement proteins is a 150-residue-long C-terminal extension of
      their alpha-subunits that harbors three internal disulfide bonds. Previous
      reports have suggested that this is an independent structural module, homologous
      to modules found in other proteins, including netrins and tissue inhibitors of
      metalloproteinases. Because of its distribution, this putative module has been
      named both C345C and NTR. To assess the structures of these segments of the
      complement proteins, their relationships with other domains, and activities as
      independent structures, we expressed C345C from C3 and C5 in a bacterial strain
      that permits cytoplasmic disulfide bond formation. Affinity purification directly
      from cell lysates yielded recombinant C3- and C5-C345C with properties consistent
      with multiple intramolecular disulfide bonds and high beta-sheet contents. rC5-,
      but not rC3-C345C inhibited complement hemolytic activity, and surface plasmon
      resonance studies revealed that rC5-C345C binds to complement components C6 and
      C7 with dissociation constants of 10 and 3 nM, respectively. Our results provide
      strong evidence that this binding corresponds to the previously described
      reversible binding of C5 to C6 and C7, and taken together with earlier work,
      indicate that the C5-C345C module interacts directly with the factor I modules in
      C6 and C7. The high binding affinities suggest that complexes composed of C5
      bound to C6 or C7 exist in plasma before activation and may facilitate assembly
      of the complement membrane attack complex.

PMID- 14662859
TI  - Identification of a critical Ig-like domain in IL-18 receptor alpha and
      characterization of a functional IL-18 receptor complex.
AB  - Steady state mRNA levels in various human tissues reveal that the proinflammatory
      cytokine IL-18 is constitutively and ubiquitously expressed. However, limited IL
      18R alpha-chain (IL-18Ralpha) expression in tissues may restrict ligand-acting
      sites and contribute to a specific response for IL-18. To study the IL-18R
      complex, [(125)I]IL-18 was studied for binding to the cell surface receptors of
      IL-18-responsive NK and macrophagic KG-1 cells. After cross-linking, [(125)I]IL
      18 formed three IL-18R complexes with sizes of approximately 93, 160, and 220
      kDa. In KG-1 cells, Scatchard analysis revealed the presence of 135 binding
      sites/cell, with an apparent dissociation constant (K(d)) of 250 pM; in NK cells,
      there were 350 binding sites per cell with an apparent K(d) of 146 pM. Each
      domain of extracellular IL-18Ralpha was cloned and individually expressed in
      Escherichia coli. An mAb specifically recognized the membrane-proximal third
      domain; this mAb blocked IL-18-induced IFN-gamma production in NK cells.
      Furthermore, deletion of the membrane-proximal third domain of IL-18Ralpha
      prevented the formation of IL-18R ternary complex with IL-18R beta-chain. The
      present studies demonstrate that the biologically active IL-18R complex requires
      the membrane-proximal third Ig-like domain in IL-18Ralpha for the formation of IL
      18R ternary complex as well as for signal transduction involved in IL-18-induced
      IFN-gamma in NK cells.

PMID- 14662860
TI  - Regulation of inducible nitric oxide synthase expression by p300 and p50
      acetylation.
AB  - To determine whether p300 is involved in inducible NO synthase (iNOS)
      transcriptional regulation, we evaluated the effect of p300 overexpression on
      iNOS expression and characterized p300 binding to iNOS promoter in RAW 264.7
      cells. p300 overexpression increased iNOS expression which was abrogated by
      deletion of the histone acetyltransferase (HAT) domain (Delta1472-1522). DNA
      binding and chromatin immunoprecipitation assays revealed binding of p300 to
      several DNA-bound transactivators at basal state. Following stimulation with LPS
      plus IFN-gamma, binding of p300, p50/p65 NF-kappaB, and IFN-regulatory factor-1
      was increased by approximately 2-fold. Nuclear p50 was complexed with and
      acetylated by p300 at the basal binding state which was increased by LPS and IFN
      gamma stimulation. p300 overexpression resulted in increased p50 acetylation
      which was reduced by HAT mutation. p50 acetylation correlated with increased NF
      kappaB binding and enhanced p300 recruitment. Co-overexpression of E1A abolished
      the augmentation of p50 acetylation and p50 binding induced by p300
      overexpression, and a correlative suppression of p300 recruitment to the complex.
      We conclude that p300 is essential for iNOS transcription. Our results suggest
      that p300 HAT acetylates the p50 subunit of NF-kappaB, thereby increasing NF
      kappaB binding and NF-kappaB mediated transactivation.

PMID- 14662861
TI  - Critical role for the Oct-2/OCA-B partnership in Ig-secreting cells.
AB  - B and T lymphocytes arise from a common precursor in the bone marrow, but
      ultimately acquire very different functions. The difference in function is
      largely attributable to the expression of tissue-specific transcription factors
      that activate discrete sets of genes. In previous studies we and others have
      shown that the specialized genes expressed by Ig-secreting cells cease
      transcription when these cells are fused to a T lymphoma. The extinguished genes
      include those encoding Ig, J chain, and the transcription factors Oct-2, PU.1,
      and the coactivator OCA-B. Remarkably, if we sustain Oct-2 expression during cell
      fusion, all the other tissue-specific genes of the Ig-secreting cell
      simultaneously escape silencing. This suggests that Oct-2 plays a central role in
      maintaining the gene expression program of these cells. In the present studies we
      have investigated the roles of the transcription factor PU.1 and the coactivator
      OCA-B within the hierarchy of regulatory factors that sustain Ig-secreting cell
      function. Our results show that OCA-B and Oct-2 are regulatory partners in this
      process and that PU.1 plays a subordinate role at this cell stage.

PMID- 14662862
TI  - Identification, isolation, and culture of HLA-A2-specific B lymphocytes using MHC
      class I tetramers.
AB  - Characterizing the individual B cells that participate in the production of anti
      HLA Abs requires isolation and culture of these cells and a suitable assay for
      detection of Abs produced in these B cell cultures. We previously showed that B
      cell precursors, programmed for anti-HLA Ab secretion, are present at measurable
      frequencies in peripheral blood of women immunized by pregnancy. In this study,
      we show that tetrameric HLA-A2, although designed for characterization of CTLs,
      provides a suitable affinity ligand for isolation of allospecific B cells, which
      subsequently can be induced to produce HLA-A2 Ab in a CD40-driven culture system.
      The validity of this concept was established by assaying human hybridomas,
      producing anti-HLA Abs, for specific tetrameric HLA-A2 binding. The availability
      of anti-HLA Ab-producing B cell cultures that are established without
      immortalization will be of value when T-B cell interaction is studied at an
      alloantigen-specific level.

PMID- 14662863
TI  - The B12/23 restriction is critically dependent on recombination signal nonamer
      and spacer sequences.
AB  - Ag receptor variable region gene assembly is initiated through the formation of a
      synaptic complex which minimally includes the recombination-activating gene (RAG)
      1/2 proteins and a pair of recombination signals (RSs) flanking the recombining
      gene segments. RSs are composed of conserved heptamer and nonamer sequences
      flanking relatively nonconserved spacers of 12 or 23 bp. RSs regulate variable
      region gene assembly within the context of the 12/23 rule which mandates that
      recombination only occurs between RSs of dissimilar spacer length. RSs can exert
      additional constraints on variable region gene assembly beyond imposing spacer
      length requirements. At a minimum this restriction, termed B12/23, is imposed on
      the Vbeta to DJbeta rearrangement step by the 5' Dbeta RS and is enforced at or
      before the DNA cleavage step of the V(D)J recombination reaction. In this study,
      the components of the 5' Dbeta RS required for enforcing the B12/23 rule are
      assessed on chromosomal substrates in vivo in the context of normal murine
      thymocyte development and on extrachromosomal substrates induced to undergo
      recombination in nonlymphoid cell lines. These analyses reveal that the integrity
      of the nonamer sequence as well as the highly conserved spacer nucleotides of the
      5' Dbeta1 RS are critical for enforcing the B12/23 restriction. These findings
      have important implications for understanding the B12/23 restriction and the
      manner in which RS synaptic complexes are assembled in vivo.

PMID- 14662864
TI  - Transcriptional regulation of ILT family receptors.
AB  - Ig-like transcripts (ILT/leukocyte Ig-like receptor/monocyte/macrophage Ig-like
      receptor or CD85) are encoded on human chromosome 19q13.4, designated the human
      leukocyte receptor complex, and are predominantly expressed on myeloid lineage
      cells. We investigated the transcriptional regulation of ILT1, ILT2, and ILT4
      genes to elucidate control mechanisms operating on the specific expression of ILT
      receptors. Inhibitory ILT2 and ILT4 both have a similar genomic structure, in
      which the approximately 160-bp 5'-flanking regions function as core promoters
      with critically important PU.1 binding sites. However, an Sp1 family-binding GC
      box is more influential in trans-activation of ILT2 than ILT4. Additionally, ILT4
      transcription is tightly regulated by chromatin modifications accompanied by
      histone acetylation, which strictly controls expression within myeloid lineage
      cells. Activating ILT1 carries a core promoter corresponding to the intronic
      region of ILT2 and ILT4, where PU.1 and Runx1 binding sites are essential, but a
      downstream heat shock element also augments promoter activity. Thus, each ILT is
      regulated by a distinct transcriptional mechanism, although PU.1 acts as a common
      trans-acting factor. We also found that human CMV infection strongly trans
      activates inhibitory ILT2 and ILT4 genes through the expression of immediate
      early proteins.

PMID- 14662865
TI  - Transcriptional regulation of Src homology 2 domain-containing leukocyte
      phosphoprotein of 76 kDa: dissection of key promoter elements.
AB  - SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) is
      an adaptor molecule expressed in all hemopoietic cell lineages except mature B
      cells and is known to play critical roles in the function of T cells, mast cells,
      and platelets and in vascular differentiation. Although great progress has been
      achieved in our understanding of SLP-76 function, little is known about the
      mechanisms regulating its expression. In this study we report the initial
      characterization of essential elements that control SLP-76 transcription. We
      identify several DNase I-hypersensitive sites in the SLP-76 locus, with a
      prominent site located in its promoter region. This site exists in T cells and
      monocytic cells, but not in B cells or fibroblasts. Using transient transfection
      assays, we identify a 507-bp fragment containing the 5'-untranslated region of
      the first exon and the immediate upstream sequence that confers transcriptional
      activation in T cells and monocytic cells, but not in B cells. Analysis of the 5'
      ends of SLP-76 transcripts reveals differential regulation of SLP-76
      transcription initiation between T cells and monocytic cells. Mutational and gel
      shift analyses further indicate a critical role within this region for a binding
      site for Ets family transcription factors. The present study provides the first
      data to address the mechanisms controlling SLP-76 transcription by providing
      evidence for several key cis-regulatory elements in the promoter region.

PMID- 14662866
TI  - Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial
      cells by IL-1 beta, but not by TNF-alpha.
AB  - Synthesis of the antimicrobial protein neutrophil gelatinase-associated lipocalin
      (NGAL) increases dramatically in bronchial epithelial cells and alveolear type II
      pneumocytes during lung inflammation. IL-1beta induces a >10-fold up-regulation
      of NGAL expression in the type II pneumocyte-derived cell line A549 cells,
      whereas TNF-alpha, IL-6, and LPS had no effect. Similar IL-1beta selectivity was
      demonstrated in primary bronchial epithelial cells and epidermal keratinocytes
      and for an NGAL promoter fragment transfected into A549 cells. By deletion and
      substitution analysis of the NGAL promoter, a 40-bp region containing an NF
      kappaB consensus site was found to control the IL-1beta-specific up-regulation.
      Involvement of the NF-kappaB site was demonstrated by site-directed mutagenesis,
      by transfection with a dominant-negative inhibitor of the NF-kappaB pathway, and
      by EMSA. TNF-alpha activation of NF-kappaB, in contrast, did not increase NGAL
      synthesis, even though induced binding of NF-kappaB to the NGAL promoter was
      observed in vitro. IL-1beta specificity was not contained within the NF-kappaB
      site of the NGAL promoter, as determined by exchanging the NGAL promoter's NF
      kappaB-binding sequence with that of the IL-8 promoter or with the NF-kappaB
      consensus sequence and by testing the NF-kappaB-binding sequence of the NGAL
      promoter against the heterologous SV40 promoter. Selectivity for the IL-1 pathway
      was substantiated by demonstrating that NGAL promoter activity could be induced
      by LPS stimulation of A549 cells transiently expressing Toll-like receptor 4,
      which use the same intracellular signaling pathway as the IL-1R. Together, this
      demonstrates a selective up-regulation of NGAL by the IL-1 pathway.

PMID- 14662867
TI  - The protein made from a common allele of KIR3DL1 (3DL1*004) is poorly expressed
      at cell surfaces due to substitution at positions 86 in Ig domain 0 and 182 in Ig
      domain 1.
AB  - KIR3DL1 is an inhibitory HLA-B receptor of human NK and T cells that exhibits
      genetic and phenotypic polymorphism. KIR3DL1*004, a common allotype, cannot be
      detected on the surface of PBLs using the KIR3DL1-specific Ab DX9. The nature of
      this phenotype was investigated through comparison of 3DL1*004 with 3DL1*002, an
      allele giving high DX9 binding to cell surfaces. Analysis of Jurkat T cell
      transfectants with 3DL1*004 cDNA showed that 3DL1*004 is poorly expressed at the
      cell surface, but detectable intracellularly. Analysis of recombinant mutants
      made between 3DL1*004 and 3DL1*002 showed that polymorphism in Ig domains 0 and 1
      (D0 and D1) causes the intracellular retention of 3DL1*004. Reciprocal point
      mutations were introduced into 3DL1*004 and 3DL1*002 at positions 44 and 86 of
      the D0 domain, where 3DL1*004 has unique residues, and at position 182 of the D1
      domain, where 3DL1*004 resembles 3DL1*005, an allotype giving low DX9-binding
      phenotype. Leucine 86 in 3DL1*004 is the principal cause of its intracellular
      retention, with a secondary and additive contribution from serine 182. By
      contrast, glycine 44, which is naturally present in 3DL1*004, slightly increased
      cell surface expression when introduced into 3DL1*002. In 3DL1*004, the presence
      of leucine at position 86 corrupts the WSXPS motif implicated in proper folding
      of the KIR D0 Ig-like domain. This study demonstrates how a difference between
      KIR3DL1 allotypes in the D0 domain profoundly affects cell surface expression and
      function.

PMID- 14662868
TI  - Anti-CD8 antibodies can inhibit or enhance peptide-MHC class I (pMHCI) multimer
      binding: this is paralleled by their effects on CTL activation and occurs in the
      absence of an interaction between pMHCI and CD8 on the cell surface.
AB  - Cytotoxic T lymphocytes recognize short peptides presented in association with
      MHC class I (MHCI) molecules on the surface of target cells. The Ag specificity
      of T lymphocytes is conferred by the TCR, but invariable regions of the peptide
      MHCI (pMHCI) molecule also interact with the cell surface glycoprotein CD8. The
      distinct binding sites for CD8 and the TCR allow pMHCI to be bound simultaneously
      by both molecules. Even before it was established that the TCR recognized pMHCI,
      it was shown that CTL exhibit clonal heterogeneity in their ability to activate
      in the presence of anti-CD8 Abs. These Ab-based studies have since been
      interpreted in the context of the interaction between pMHCI and CD8 and have
      recently been extended to show that anti-CD8 Ab can affect the cell surface
      binding of multimerized pMHCI Ags. In this study, we examine the role of CD8
      further using point-mutated pMHCI Ag and show that anti-CD8 Abs can either
      enhance or inhibit the activation of CTL and the stable cell surface binding of
      multimerized pMHCI, regardless of whether there is a pMHCI/CD8 interaction. We
      further demonstrate that multimerized pMHCI Ag can recruit CD8 in the absence of
      a pMHCI/CD8 interaction and that anti-CD8 Abs can generate an intracellular
      activation signal resulting in CTL effector function. These results question many
      previous assumptions as to how anti-CD8 Abs must function and indicate that CD8
      has multiple roles in CTL activation that are not necessarily dependent on an
      interaction with pMHCI.

PMID- 14662869
TI  - Homotypic secretory vesicle fusion induced by the protein tyrosine phosphatase
      MEG2 depends on polyphosphoinositides in T cells.
AB  - Sec14p homology domains are found in a large number of proteins from plants,
      yeast, invertebrates, and higher eukaryotes. We report that the N-terminal Sec14p
      homology domain of the human protein tyrosine phosphatase PTP-MEG2 binds
      phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) in vitro and
      colocalizes with this lipid on secretory vesicle membranes in intact cells. Point
      mutations that prevented PtdIns(3,4,5)P(3) binding abrogated the capacity of PTP
      MEG2 to induce homotypic secretory vesicle fusion in cells. Inhibition of
      cellular PtdIns(3,4,5)P(3) synthesis also rapidly reversed the effect of PTP-MEG2
      on secretory vesicles. Finally, we show that several different phosphoinositide
      kinases colocalize with PTP-MEG2, thus allowing for local synthesis of
      PtdIns(3,4,5)P(3) in secretory vesicle membranes. We suggest that PTP-MEG2
      through its Sec14p homology domain couples inositide phosphorylation to tyrosine
      dephosphorylation and the regulation of intracellular traffic of the secretory
      pathway in T cells.

PMID- 14662870
TI  - Basal chromatin modification at the IL-4 gene in helper T cells.
AB  - Chromatin immunoprecipitations in naive CD4, but not CD8, T cells, demonstrated
      association of the IL-4 promoter with acetylated histone. Histone modifications
      and rapid IL-4 transcription were absent in conserved noncoding sequence 1 (CNS
      1)(-/-) cells lacking an 8-kb-distant enhancer in the IL-4/IL-13 intergenic
      region, but also in CD4(-/-) and Itk(-/-) cells, which have similar Th2
      deficiencies. Histones associated with the IL-13 promoter were not similarly
      acetylated in naive T cells, but became acetylated in differentiated Th2 cells.
      Conversely, Th1 differentiation induced histone methylation at the type 2
      cytokine locus. Like CD4(-/-) and Itk(-/-) mice, CNS-1(-/-) BALB/c mice were
      highly resistant to the Th2-inducing protozoan, Leishmania major. CNS-1
      deficiency led to failure of IL-4 gene repositioning to heterochromatin after Th1
      polarization, possibly related to the presence of reiterative Ikaros binding
      sites in the intergenic element. Hyperacetylation of nonexpressed genes may serve
      to mark lineage-specific loci for rapid expression and further modification.

PMID- 14662871
TI  - Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling
      are present in human plasma and breast milk.
AB  - Dysregulation of the initial, innate immune response to bacterial infection may
      lead to septic shock and death. Toll-like receptors (TLRs) play a crucial role in
      this innate immune response, and yet the regulatory mechanisms controlling
      microbial-induced TLR triggering are still to be fully understood. We have
      therefore sought specific regulatory mechanisms that may modulate TLR signaling.
      In this study, we tested for the possible existence of a functionally active
      soluble form of TLR2. We demonstrated the existence of natural soluble forms of
      TLR2 (sTLR2), which we show to be capable of modulating cell activation. We found
      that blood monocytes released sTLR2 constitutively and that the kinetics of sTLR2
      release increased upon cell activation. Analysis of cells expressing the human
      TLR2 cDNA or its c-myc-tagged version indicated that sTLR2 resulted from the
      posttranslational modification of the TLR2 protein in an intracellular
      compartment. Moreover, an intracellular pool of sTLR2 is maintained. sTLR2 was
      found naturally expressed in breast milk and plasma. Milk sTLR2 levels mirrored
      those of the TLR coreceptor soluble CD14. Depletion of sTLR2 from serum resulted
      in an increased cellular response to bacterial lipopeptide. Notably, serum sTLR2
      was lower in tuberculosis patients. Coimmunoprecipitation experiments and
      computational molecular docking studies showed an interaction between sTLR2 and
      soluble CD14 in plasma and milk. These findings suggest the existence of a novel
      and specific innate immune mechanism regulating microbial-induced TLR triggering,
      and may lead to new therapeutics for the prevention and/or treatment of severe
      infectious diseases.

PMID- 14662872
TI  - The antimicrobial peptide LL-37 activates innate immunity at the airway
      epithelial surface by transactivation of the epidermal growth factor receptor.
AB  - Antimicrobial peptides produced by epithelial cells and neutrophils represent
      essential elements of innate immunity, and include the defensin and cathelicidin
      family of antimicrobial polypeptides. The human cathelicidin cationic
      antimicrobial protein-18 is an antimicrobial peptide precursor predominantly
      expressed in neutrophils, and its active peptide LL-37 is released from the
      precursor through the action of neutrophil serine proteinases. LL-37 has been
      shown to display antimicrobial activity against a broad spectrum of
      microorganisms, to neutralize LPS bioactivity, and to chemoattract neutrophils,
      monocytes, mast cells, and T cells. In this study we show that LL-37 activates
      airway epithelial cells as demonstrated by activation of the mitogen-activated
      protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and increased
      release of IL-8. Epithelial cell activation was inhibited by the MAPK/ERK kinase
      (MEK) inhibitors PD98059 and U0126, by the epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitor AG1478, by blocking anti-EGFR and anti-EGFR
      ligand Abs, and by the metalloproteinase inhibitor GM6001. These data suggest
      that LL-37 transactivates the EGFR via metalloproteinase-mediated cleavage of
      membrane-anchored EGFR-ligands. LL-37 may thus constitute one of the mediators by
      which neutrophils regulate epithelial cell activity in the lung.

PMID- 14662873
TI  - Outer membrane protein A from Klebsiella pneumoniae activates bronchial
      epithelial cells: implication in neutrophil recruitment.
AB  - Aside from its mechanical barrier function, bronchial epithelium plays an
      important role both in the host defense and in the pathogenesis of inflammatory
      airway disorders. To investigate its role in lung defense, the effect of a
      bacterial cell wall protein, the outer membrane protein A from Klebsiella
      pneumoniae (kpOmpA) on bronchial epithelial cells (BEC) was evaluated on adhesion
      molecule expression and cytokine production. Moreover, the potential implication
      of this mechanism in kpOmpA-induced lung inflammation was also determined. Our in
      vitro studies demonstrated that kpOmpA strongly bound to BEAS-2B cells, a human
      BEC line, and to BEC primary cultures, resulting in NF-kappaB signaling pathway
      activation. Exposure to kpOmpA increased ICAM-1 mRNA and cell surface expression,
      as well as the secretion of IL-6, CXC chemokine ligand (CXCL)1, CXCL8, C-C
      chemokine ligand 2, CXCL10 by BEAS-2B cells, and BEC primary cultures (p <
      0.005). We analyzed in vivo the consequences of intratracheal injection of kpOmpA
      to BALB/c mice. In kpOmpA-treated mice, a transient neutrophilia (with a maximum
      at 24 h) was observed in bronchoalveolar lavage and lung sections. In vivo kpOmpA
      priming induced bronchial epithelium activation as evaluated by ICAM-1 and CXCL1
      expression, associated with the secretion of CXCL1 and CXCL5 in bronchoalveolar
      lavage fluids. In the lung, an increased level of the IL-6, CXCL1, CXCL5, CXCL10
      mRNA was observed with a maximum at 6 h. These data showed that kpOmpA is
      involved in host defense mechanism by its ability to activate not only APC but
      also BEC, resulting in a lung neutrophilia.

PMID- 14662874
TI  - Leishmania-induced inhibition of macrophage antigen presentation analyzed at the
      single-cell level.
AB  - A number of studies have previously examined the capacity of intracellular
      Leishmania parasites to modulate the capacity of macrophages to process and
      present Ags to MHC class II-restricted CD4(+) T cells. However, the bulk culture
      approaches used for assessing T cell activation make interpretation of some of
      these studies difficult. To gain a more precise understanding of the interaction
      between Leishmania-infected macrophages and effector T cells, we have analyzed
      various parameters of T cell activation in individual macrophage-T cell
      conjugates. Leishmania-infected macrophages efficiently stimulate Ag-independent
      as well as Ag-dependent, TCR-mediated capping of cortical F-actin in DO.11 T
      cells. However, infected macrophages are less efficient at promoting the
      sustained TCR signaling necessary for reorientation of the T cell microtubule
      organizing center and for IFN-gamma production. A reduced ability to activate
      these T cell responses was not due to altered levels of surface-expressed MHC
      class II-peptide complexes. This study represents the first direct single-cell
      analysis of the impact of intracellular infection on the interaction of
      macrophages with T cells and serves to emphasize the subtle influence Leishmania
      has on APC function.

PMID- 14662875
TI  - IL-8-mediated cell migration in endothelial cells depends on cathepsin B activity
      and transactivation of the epidermal growth factor receptor.
AB  - Microvascular endothelial cells (HMECs) express both the CXCR1 and the CXCR2, but
      cell migration is almost entirely mediated by the CXCR2. Similarly, NIH 3T3 cells
      transfected with the CXCR2 migrated toward IL-8, whereas CXCR1-transfected cells
      failed to do so. This situation differs from that seen in leukocytes, where
      chemotaxis is primarily a function of the CXCR1. To define signal transduction
      pathways that explain this difference in behavior, various inhibitors were used
      to block cell migration. Apart from inhibitors of phosphatidylinositol 3-kinase,
      which blocked migration in all cases, inhibition of the epidermal growth factor
      (EGF) receptor blocked IL-8-mediated cell migration in HMECs and in CXCR2
      transfected NIH 3T3 cells, but not in RBL2H3 cells, which do not express an EGFR.
      Blocking Abs against the EGFR or against heparin-binding EGF-like growth factor
      similarly blocked IL-8-mediated cell migration and in vitro tubulogenesis in
      HMECs. Furthermore, inhibition of the EGFR also attenuated focus formation in NIH
      3T3 expressing the CXCR2. Immunoprecipitations of the EGFR in HMECs and in NIH
      3T3 cells expressing the CXCR2 confirmed that the EGFR was phosphorylated
      following stimulation with IL-8. However, in contrast to previous reports, e.g.,
      for the thrombin receptor, inhibition of matrix metalloproteases blocked IL-8
      mediated cell migration only partially, whereas it was ablated by inhibition of
      cathepsin B. These results indicate that IL-8-induced transactivation of the EGFR
      is mediated by the CXCR2 and involves cathepsin B, and that this pathway is
      important for the migratory and tumorigenic effects of IL-8.

PMID- 14662876
TI  - Proinflammatory cytokines dominate the early immune response to filarial
      parasites.
AB  - Although the early human immune response to the infective-stage larvae (L3) of
      Brugia malayi has not been well-characterized in vivo (because of the inability
      to determine the precise time of infection), the consensus has been that it must
      involve a predominant Th2 environment. We have set up an in vitro system to study
      this early immune response by culturing PBMC from unexposed individuals with live
      L3 of B. malayi. After 24 h of culture, T cell responses were examined by flow
      cytometry and by quantitative real-time RT-PCR for multiple cytokines. T cells
      were activated early following exposure to L3 as indicated by up-regulation of
      surface markers CD69 and CD71. The frequency of T cells expressing
      proinflammatory Th1 cytokines (IFN-gamma, TNF-alpha, GM-CSF, IL-1alpha, and IL-8)
      but not Th2 cytokines (IL-4, IL-5, IL-6, IL-10, and IL-13) was significantly
      increased in response to L3. This T cell response occurred in both the CD4 and
      CD8 T cell compartment and was restricted to the effector/memory pool
      (CD45RO(+)). This T cell response was not due to LPS activity from the parasite
      or from its endosymbiont, Wolbachia; moreover, it required the presence of APC as
      well as direct contact with live L3. Real-time RT-PCR analysis of multiple
      cytokines in the T cells confirmed the increased expression of proinflammatory
      Th1 cytokines. Up-regulation of these cytokines suggests that the primary immune
      response to the live infective stage of the parasite is not predominantly Th2 in
      nature but rather dominated by a proinflammatory response.

PMID- 14662877
TI  - CTL are inactivated by herpes simplex virus-infected cells expressing a viral
      protein kinase.
AB  - Numerous cell-to-cell signals tightly regulate CTL function. Human fibroblasts
      infected with HSV type 1 or 2 can generate such a signal and inactivate human
      CTL. Inactivated CTL lose their ability to release cytotoxic granules and
      synthesize cytokines when triggered through the TCR. Inactivation requires cell
      to-cell contact between CTL and HSV-infected cells. However, inactivated CTL are
      not infected with HSV. The inactivation of CTL is sustainable, as CTL function
      remains impaired when the CTL are removed from the HSV-infected cells. IL-2
      treatment does not alter inactivation, and the inactivated phenotype is not
      transferable between CTL, distinguishing this phenotype from traditional anergy
      and T regulatory cell models. CTL inactivated by HSV-infected cells are not
      apoptotic, and the inactivated state can be overcome by phorbol ester
      stimulation, suggesting that inactivated CTL are viable and that the signaling
      block is specific to the TCR. HSV-infected cells require the expression of U(S)3,
      a viral protein kinase, to transmit the inactivating signal. Elucidation of the
      molecular nature of this signaling pathway may allow targeted manipulation of CTL
      function.

PMID- 14662878
TI  - Salmonella rapidly kill dendritic cells via a caspase-1-dependent mechanism.
AB  - Dendritic cells provide a critical link between innate and acquired immunity. In
      this study, we demonstrate that the bacterial pathogen Salmonella enterica
      serovar Typhimurium can efficiently kill these professional phagocytes via a
      mechanism that is dependent on sipB and the Salmonella pathogenicity island 1
      encoded type III protein secretion system. Rapid phosphatidylserine
      redistribution, caspase activation, and loss of plasma membrane integrity were
      characteristic of dendritic cells infected with wild-type Salmonella, but not
      sipB mutant bacteria. Caspase-1 was particularly important in this process
      because Salmonella-induced dendritic cell death was dramatically reduced in the
      presence of a caspase-1-specific inhibitor. Furthermore, dendritic cells obtained
      from caspase-1-deficient mice, but not heterozygous littermate control mice, were
      resistant to Salmonella-induced cytotoxicity. We hypothesize that Salmonella have
      evolved the ability to selectively kill professional APCs to combat, exploit, or
      evade immune defense mechanisms.

PMID- 14662879
TI  - CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma
      through a TNF-alpha-dependent mechanism.
AB  - Protection against certain intracellular pathogens can take place in the absence
      of IFN-gamma through mechanisms dependent on TNF-alpha. In this regard, patients
      with partial defect in IFN-gamma receptor 1 are not susceptible to toxoplasmosis.
      Thus, we used a model of Toxoplasma gondii infection to investigate whether CD154
      modulates IFN-gamma-independent mechanisms of host protection. Human monocyte
      derived macrophages treated with recombinant CD154 exhibited increased anti-T.
      gondii activity. The number of tachyzoites per 100 macrophages at 20 h
      postinfection was lower in CD154-treated macrophages compared with controls. This
      was accompanied by a decrease in the percentage of infected cells in CD154
      treated macrophages at 20 h compared with 1 h postinfection. CD154-bearing cells
      also induced antimicrobial activity in T. gondii-infected macrophages. CD154
      enhanced macrophage anti-T. gondii activity independently of IFN-gamma. TNF-alpha
      mediated the effects of CD154 on macrophage anti-T. gondii activity. CD154
      increased TNF-alpha production by T. gondii-infected macrophages, and
      neutralization of TNF-alpha inhibited the effect of CD154 on macrophage anti-T.
      gondii activity. These results demonstrate that CD154 triggers TNF-alpha
      dependent antimicrobial activity in macrophages and suggest that CD154 regulates
      the mechanisms of host protection that take place when IFN-gamma signaling is
      deficient.

PMID- 14662880
TI  - Human cytomegalovirus-encoded US2 differentially affects surface expression of
      MHC class I locus products and targets membrane-bound, but not soluble HLA-G1 for
      degradation.
AB  - Human CMV (HCMV) can elude CTL as well as NK cells by modulating surface
      expression of MHC class I molecules. This strategy would be most efficient if the
      virus would selectively down-regulate viral Ag-presenting alleles, while at the
      same time preserving other alleles to act as inhibitors of NK cell activation. We
      focused on the HCMV unique short (US) region encoded protein US2, which binds to
      newly synthesized MHC class I H chains and supports their dislocation to the
      cytosol for subsequent degradation by proteasomes. We studied the effect of US2
      on surface expression of individual class I locus products using flow cytometry.
      Our results were combined with crystal structure data of complexed US2/HLA
      A2/beta(2)-microglobulin and alignments of 948 HLA class I database sequences of
      the endoplasmic reticulum lumenal region inplicated in US2 binding. This study
      suggests that surface expression of all HLA-A and -G and most HLA-B alleles will
      be affected by US2. Several HLA-B alleles and all HLA-C and -E alleles are likely
      to be insensitive to US2-mediated degradation. We also found that the MHC class I
      endoplasmic reticulum-lumenal domain alone is not sufficient for degradation by
      US2, as illustrated by the stability of soluble HLA-G1 in the presence of US2.
      Furthermore, we showed that the membrane-bound HLA-G1 isoform, but also tailless
      HLA-A2, are targeted for degradation. This indicates that the cytoplasmic tail of
      the MHC class I H chain is not required for its dislocation to the cytosol by
      US2.

PMID- 14662881
TI  - Mycobacterium avium inhibition of IFN-gamma signaling in mouse macrophages: Toll
      like receptor 2 stimulation increases expression of dominant-negative STAT1 beta
      by mRNA stabilization.
AB  - Mycobacterial infections of macrophages have been shown to inhibit the ability of
      the macrophage to respond to IFN-gamma. We previously reported that Mycobacterium
      avium infection of mouse macrophages decreases IFN-gamma-induced STAT1 tyrosine
      phosphorylation and STAT1 DNA binding. Because macrophages respond to M. avium
      through Toll-like receptor 2 (TLR2), we determined whether TLR2 stimulation
      inhibits the response to IFN-gamma. Treatment of mouse RAW264.7 macrophages with
      TLR2 agonists inhibited the induction of IFN-gamma-inducible genes by IFN-gamma.
      In contrast to M. avium infection, TLR2 agonists did not inhibit the IFN-gamma
      induction of DNA-binding activity of STAT1 and the tyrosine phosphorylation of
      STAT1alpha. Instead, IFN-gamma induction of RAW264.7 cells treated with TLR2
      agonists resulted in an increase in the tyrosine phosphorylation of the dominant
      negative STAT1beta. TLR2 stimulation of RAW264.7 cells increased both STAT1beta
      protein and mRNA expression, suggesting that the increased STAT1beta
      phosphorylation results from increased STAT1beta expression. Because STAT1alpha
      and STAT1beta mRNA have different 3' untranslated regions, and 3' untranslated
      regions can regulate mRNA stability, we examined the effects of TLR2 stimulation
      on mRNA stability. TLR2 stimulation of RAW264.7 cells increased the stability of
      STAT1beta mRNA, while not affecting the stability of STAT1alpha mRNA. The ability
      of STAT1beta to function as a dominant negative was confirmed by overexpression
      of STAT1beta in RAW264.7 macrophages by transient transfection, which inhibited
      IFN-gamma-induced gene expression. These findings suggest that M. avium infection
      of mouse macrophages inhibits IFN-gamma signaling through a TLR2-dependent
      increase in STAT1beta expression by mRNA stablization and a TLR2-independent
      inhibition of STAT1 tyrosine phosphorylation.

PMID- 14662882
TI  - Induction of CD8+ T cells to an HIV-1 antigen through a prime boost regimen with
      heterologous E1-deleted adenoviral vaccine carriers.
AB  - E1-deleted adenoviral recombinants most commonly based on the human serotype 5
      (AdHu5) have been shown thus far to induce unsurpassed transgene product-specific
      CD8(+) T cell responses. A large percentage of the adult human population carries
      neutralizing Abs due to natural exposures to AdHu5 virus. To circumvent reduction
      of the efficacy of adenovirus (Ad) vector-based vaccines by neutralizing Abs to
      the vaccine carrier, we developed E1-deleted adenoviral vaccine carriers based on
      simian serotypes. One of these carriers, termed AdC68, expressing a codon
      optimized truncated form of gag of HIV-1 was shown previously to induce a potent
      transgene product-specific CD8(+) T cell response in mice. We constructed a
      second chimpanzee adenovirus vaccine vector, termed AdC6, also expressing the
      truncated gag of HIV-1. This vector, which belongs to a different serotype than
      the AdC68 virus, induces high frequencies of gag-specific CD8(+) T cells in mice
      including those pre-exposed to AdHu5 virus. Generation of an additional E1
      deleted adenoviral vector of chimpanzee origin allows for sequential booster
      immunizations with heterologous vaccine carriers. In this study, we show that
      such heterologous prime boost regimens based on E1-deleted adenoviral vectors of
      different serotypes expressing the same transgene product are highly efficient in
      increasing the transgene product-specific CD8(+) T cell response. They are
      equivalent to sequential vaccinations with an E1-deleted Ad vector followed by
      booster immunization with a poxvirus vector and they surpass regimens based on
      DNA vaccine prime followed by a recombinant adenoviral vector boost.

PMID- 14662883
TI  - Hyaluronic acid or TNF-alpha plus fibronectin triggers granulocyte macrophage
      colony-stimulating factor mRNA stabilization in eosinophils yet engages
      differential intracellular pathways and mRNA binding proteins.
AB  - Eosinophils (Eos) accumulate in airways and lung parenchyma of active asthmatics.
      GM-CSF is a potent inhibitor of Eos apoptosis both in vitro and in vivo and is
      produced by activated fibroblasts, mast cells, T lymphocytes as well as Eos.
      Cytokine release by Eos is preceded by GM-CSF mRNA stabilization induced by TNF
      alpha plus fibronectin. Hyaluronic acid (HA) is a major extracellular matrix
      proteoglycan, which also accumulates in the lung during asthma exacerbations. In
      this study we have analyzed the effects of HA on Eos survival and GM-CSF
      expression. We demonstrate that like TNF-alpha plus fibronectin, HA stabilizes GM
      CSF mRNA, increases GM-CSF secretion, and prolongs in vitro Eos survival. GM-CSF
      mRNA stabilization accounts for most of the observed GM-CSF mRNA accumulation and
      protein production. Unlike TNF-alpha plus fibronectin, GM-CSF mRNA stabilization
      induction by HA requires continuous extracellular signal-regulated kinase
      phosphorylation. Finally, to identify potential protein regulators responsible
      for GM-CSF mRNA stabilization, immunoprecipitation-RT-PCR studies revealed
      increased GM-CSF mRNA associated with YB-1, HuR, and heterogeneous nuclear
      ribonucleoprotein (hnRNP) C after TNF-alpha plus fibronectin but only hnRNP C
      after HA. Thus, our data suggest that both TNF-alpha plus fibronectin and HA,
      which are relevant physiological effectors in asthma, contributes to long-term
      Eos survival in vivo by enhancing GM-CSF production through two different
      posttranscriptional regulatory pathways involving extracellular signal-regulated
      kinase phosphorylation and RNA binding proteins YB-1, HuR, and hnRNP C.

PMID- 14662884
TI  - Role of monocyte chemotactic protein-1/CC chemokine ligand 2 on gamma delta T
      lymphocyte trafficking during inflammation induced by lipopolysaccharide or
      Mycobacterium bovis bacille Calmette-Guerin.
AB  - Gammadelta T lymphocytes are involved in a great variety of inflammatory and
      infectious responses. However, the mechanisms by which gammadelta T lymphocytes
      migrate to inflamed sites are poorly understood. In this study we investigate the
      role of monocyte chemotactic protein (MCP)-1 in regulating gammadelta T cell
      migration after LPS or Mycobacterium bovis bacille Calmette-Guerin (BCG)
      challenge. LPS-induced gammadelta T cell influx was significantly inhibited by
      either pretreatment with dexamethasone or vaccinia virus Lister 35-kDa chemokine
      binding protein, vCKBP, a CC chemokine neutralizing protein, suggesting a role
      for CC chemokines in this phenomenon. LPS stimulation increased the expression of
      MCP-1 mRNA and protein at the inflammation site within 6 h. It is noteworthy that
      LPS was unable to increase MCP-1 production or gammadelta T cell recruitment in
      C3H/HeJ, indicative of the involvement of Toll-like receptor 4. Gammadelta T
      cells express MCP-1 receptor CCR2. Pretreatment with anti-MCP-1 mAb drastically
      inhibited LPS-induced in vivo gammadelta T cell mobilization. Indeed, MCP-1
      knockout mice were unable to recruit gammadelta T cells to the pleural cavity
      after LPS stimulation, effect that could be restored by coadministration of MCP
      1. In addition, BCG-induced gammadelta lymphocyte accumulation was significantly
      reduced in MCP-1 knockout mice when compared with wild-type mice. In conclusion,
      our results indicate that LPS-induced gammadelta T lymphocyte migration is
      dependent on Toll-like receptor 4 and sensitive to both dexamethasone and CC
      chemokine-binding protein inhibition. Moreover, by using MCP-1 neutralizing Abs
      and genetically deficient mice we show that LPS- and BCG-induced gammadelta T
      lymphocyte influx to the pleural cavity of mice is mainly orchestrated by the CC
      chemokine MCP-1.

PMID- 14662885
TI  - Surface translocation of pactolus is induced by cell activation and death, but is
      not required for neutrophil migration and function.
AB  - Pactolus is a cell surface protein expressed by murine neutrophils. Pactolus is
      similar to the beta integrins, except it lacks a functional metal ion-dependent
      adhesion site domain and is expressed without an alpha-chain partner. The
      majority of the Pactolus protein is held within the cell in dense granules in a
      highly glycosylated form. This intracellular form of Pactolus can be released to
      the cell surface following inflammatory activation or ligation of Pactolus on the
      cell surface. In addition, intracellular Pactolus translocates to the neutrophil
      surface following induction of apoptosis. Neutrophil activation studies suggest
      that Pactolus does not serve as an activating or phagocytic receptor for the
      neutrophil. To further define the function of Pactolus, a Pactolus-null mouse was
      generated. Pactolus-deficient animals mature appropriately and possess normal
      numbers of neutrophils, display appropriate migration into sites of inflammation,
      and combat introduced infections efficiently. These data suggest that Pactolus
      does not function as a neutrophil phagocytic or adhesion receptor, but may
      instead serve as a sugar-bearing ligand for lectin recognition by other cells.

PMID- 14662886
TI  - Differential activation of formyl peptide receptor-like 1 by peptide ligands.
AB  - Formyl peptide receptor-like 1 (FPRL1) plays a key role in the regulation of
      immune responses. The activation of FPRL1 induces a complicated pattern of
      cellular signaling, which results in the regulation of several immune responses,
      such as chemotactic migration and the production of reactive oxygen species
      (ROS). Because some of these cellular responses are not beneficial to the host,
      ligands that selectively modulate these cellular responses are useful. His-Phe
      Tyr-Leu-Pro-Met (HFYLPM) is a synthetic peptide that binds to FPRL1. In this
      study, we generated various HFYLPM analogues and examined their effects on
      cellular responses via FPRL1 in FPRL1-expressing rat basophilic leukemia-2H3
      cells or in primary human neutrophils. Among the HXYLPM analogues, His-Arg-Tyr
      Leu-Pro-Met (HRYLPM) activated a broad spectrum of cellular signaling events,
      including an intracellular Ca(2+) concentration increase, phosphoinositide 3
      kinase, extracellular signal-regulated kinase, and Akt activation, however, His
      Glu-Tyr-Leu-Pro-Met (HEYLPM) activated only intracellular Ca(2+) concentration
      and Akt but did not increase Ca(2+). In addition, HRYLPM was found to stimulate
      chemotaxis and ROS generation via phosphoinositide 3-kinase and an intracellular
      Ca(2+) concentration increase, respectively, whereas HEYLPM stimulated chemotaxis
      but not ROS generation. With respect to the molecular mechanisms involved in the
      differential action of HRYLPM and HEYLPM, we found that HRYLPM but not HEYLPM
      competitively inhibited the binding of (125)I-labeled Trp-Lys-Tyr-Met-Val-D-Met
      NH(2) (WKYMVm, a FPRL1 ligand) to FPRL1. This study demonstrates that the
      important chemoattractant receptor, FPRL1, may be differentially modulated by
      distinct peptide ligands. We also suggest that HRYLPM and HEYLPM may be used to
      selectively modulate FPRL1.

PMID- 14662887
TI  - Shedding of the type II IL-1 decoy receptor requires a multifunctional
      aminopeptidase, aminopeptidase regulator of TNF receptor type 1 shedding.
AB  - Proteolytic cleavage of the extracellular domain of the type II IL-1 decoy
      receptor (IL-1RII) generates soluble IL-1-binding proteins that prevent excessive
      bioactivity by binding free IL-1. In this study we report that an aminopeptidase,
      aminopeptidase regulator of TNFR1 shedding (ARTS-1), is required for IL-1RII
      shedding. Coimmunoprecipitation experiments demonstrate an association between
      endogenous membrane-associated ARTS-1 and a 47-kDa IL-1RII, consistent with
      ectodomain cleavage of the membrane-bound receptor. A direct correlation exists
      between ARTS-1 protein expression and IL-1RII shedding, as cell lines
      overexpressing ARTS-1 have increased IL-1RII shedding and decreased membrane
      associated IL-1RII. Basal IL-1RII shedding is absent from ARTS-1 knockout cell
      lines, demonstrating that ARTS-1 is required for constitutive IL-1RII shedding.
      Similarly, PMA-mediated IL-1RII shedding is almost entirely ARTS-1-dependent.
      ARTS-1 expression also enhances ionomycin-induced IL-1RII shedding. ARTS-1 did
      not alter levels of membrane-associated IL-1RI or IL-1R antagonist release from
      ARTS-1 cell lines, which suggests that the ability of ARTS-1 to promote shedding
      of IL-1R family members may be specific for IL-1RII. Further, increased IL-1RII
      shedding by ARTS-1-overexpressing cells attenuates the biological activity of IL
      1beta. We conclude that the ability of ARTS-1 to enhance IL-1RII shedding
      represents a new mechanism by which IL-1-induced cellular events can be
      modulated. As ARTS-1 also promotes the shedding of the structurally unrelated 55
      kDa, type I TNF receptor and the IL-6R, we propose that ARTS-1 may play an
      important role in regulating innate immune and inflammatory responses by
      increasing cytokine receptor shedding.

PMID- 14662888
TI  - Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells
      induces the antimicrobial peptide human beta defensin-2.
AB  - As pattern recognition receptors capable of eliciting responses to a diverse
      array of microbial products, Toll-like receptors (TLRs) participate in the
      activation of host defense mechanisms that protect against infectious pathogens.
      Given that epithelial cells lie at the interface between the host and its
      environment, we designed experiments to determine whether human airway epithelial
      cells express TLRs and respond to TLR agonists. Immunohistochemical labeling of
      TLR2 in normal human airways revealed TLR2 expression throughout the epithelium,
      with an apparently higher level of expression on noncolumnar basal epithelial
      cells. Two-color immunofluorescent labeling of TLR2 and cytokeratins 8 and 15
      revealed that TLR2 is coexpressed with the epithelial cell markers. In addition,
      airway epithelial cells grown at air-liquid interface responded to bacterial
      lipopeptide in a TLR2-dependent manner with induction of mRNA and protein of the
      antimicrobial peptide human beta defensin-2. Stimulation of epithelial cell
      cultures with lipopeptide resulted in a small and variable reduction of bacteria
      on the apical surface. Together, these data suggest that TLRs monitor epithelial
      surfaces to enhance host defense by inducing the production of an antimicrobial
      peptide.

PMID- 14662889
TI  - Peroxisome proliferator activator receptor-gamma ligands, 15-deoxy-Delta(12,14)
      prostaglandin J2 and ciglitazone, reduce systemic inflammation in polymicrobial
      sepsis by modulation of signal transduction pathways.
AB  - Peroxisome proliferator activator receptor-gamma (PPARgamma) is a nuclear
      receptor that controls the expression of several genes involved in metabolic
      homeostasis. We investigated the role of PPARgamma during the inflammatory
      response in sepsis by the use of the PPARgamma ligands, 15-deoxy-Delta(12,14)
      PGJ(2) (15d-PGJ(2)) and ciglitazone. Polymicrobial sepsis was induced by cecal
      ligation and puncture in rats and was associated with hypotension, multiple organ
      failure, and 50% mortality. PPARgamma expression was markedly reduced in lung and
      thoracic aorta after sepsis. Immunohistochemistry showed positive staining for
      nitrotyrosine and poly(ADP-ribose) synthetase in thoracic aortas. Plasma levels
      of TNF-alpha, IL-6, and IL-10 were increased. Elevated activity of
      myeloperoxidase was found in lung, colon, and liver, indicating a massive
      infiltration of neutrophils. These events were preceded by degradation of
      inhibitor kappaBalpha (IkappaBalpha), activation of IkappaB kinase complex, and c
      Jun NH(2)-terminal kinase and, subsequently, activation of NF-kappaB and AP-1 in
      the lung. In vivo treatment with ciglitazone or 15d-PGJ(2) ameliorated
      hypotension and survival, blunted cytokine production, and reduced neutrophil
      infiltration in lung, colon, and liver. These beneficial effects of the PPARgamma
      ligands were associated with the reduction of IkappaB kinase complex and c-Jun
      NH(2)-terminal kinase activation and the reduction of NF-kappaB and AP-1 DNA
      binding in the lung. Furthermore, treatment with ciglitazone or 15d-PGJ(2) up
      regulated the expression of PPARgamma in lung and thoracic aorta and abolished
      nitrotyrosine formation and poly(ADP-ribose) expression in aorta. Our data
      suggest that PPARgamma ligands attenuate the inflammatory response in sepsis
      through regulation of the NF-kappaB and AP-1 pathways.

PMID- 14662890
TI  - Among CXCR3 chemokines, IFN-gamma-inducible protein of 10 kDa (CXC chemokine
      ligand (CXCL) 10) but not monokine induced by IFN-gamma (CXCL9) imprints a
      pattern for the subsequent development of autoimmune disease.
AB  - Infection of the pancreas with lymphocytic choriomeningitis virus results in
      rapid and differential expression among CXCR3 chemokines. IFN-gamma-inducible
      protein of 10 kDa (IP-10), in contrast with monokine induced by IFN-gamma and IFN
      inducible T cell-alpha chemoattractant, is strongly expressed within 24 h
      postinfection. Blocking of IP-10, but not monokine induced by IFN-gamma, aborts
      severity of Ag-specific injury of pancreatic beta cells and abrogates type 1
      diabetes. Mechanistically, IP-10 blockade impedes the expansion of peripheral Ag
      specific T cells and hinders their migration into the pancreas. IP-10 expression
      was restricted to viruses infecting the pancreas and that are capable of causing
      diabetes. Hence, virus-induced organ-specific autoimmune diseases may be
      dependent on virus tropism and its ability to alter the local milieu by
      selectively inducing chemokines that prepare the infected tissue for the
      subsequent destruction by the adaptive immune response.

PMID- 14662891
TI  - Granulocyte-macrophage colony-stimulating factor is a chemoattractant cytokine
      for human neutrophils: involvement of the ribosomal p70 S6 kinase signaling
      pathway.
AB  - GM-CSF stimulates proliferation of myeloid precursors in bone marrow and primes
      mature leukocytes for enhanced functionality. We demonstrate that GM-CSF is a
      powerful chemotactic and chemokinetic agent for human neutrophils. GM-CSF-induced
      chemotaxis is time dependent and is specifically neutralized with Abs directed to
      either the ligand itself or its receptor. Maximal chemotactic response was
      achieved at approximately 7 nM GM-CSF, and the EC(50) was approximately 0.9 nM.
      Both concentrations are similar to the effective concentrations of IL-8 and less
      than the effective concentrations of other neutrophil chemoattractants such as
      neutrophil-activating peptide-78, granulocyte chemotactic protein-2, leukotriene
      B(4), and FMLP. GM-CSF also acts as a chemoattractant for native cells bearing
      the GM-CSF receptor, such as monocytes, as well as for GM-CSF receptor-bearing
      myeloid cell lines, HL60 (promyelomonocyte leukemic cell line) and MPD
      (myeloproliferative disorder cell line), following differentiation induction. GM
      CSF induced a rapid, transient increase in F-actin polymerization and the
      formation of focal contact rings in neutrophils, which are prerequisites for cell
      migration. The mechanism of GM-CSF-induced chemotaxis appears to involve the cell
      signaling molecule, ribosomal p70 S6 kinase (p70S6K). Both p70S6K enzymatic
      activity and T(421)/S(424) and T(389) phosphorylation are markedly increased with
      GM-CSF. In addition, the p70S6K inhibitor hamartin transduced into cells as
      active protein, interfered with GM-CSF-dependent migration, and attenuated p70S6K
      phosphorylation. These data indicate that GM-CSF exhibits chemotactic
      functionality and suggest new avenues for the investigation of the molecular
      basis of chemotaxis as it relates to inflammation and tissue injury.

PMID- 14662892
TI  - Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15
      lipoxygenase and endogenous anti-inflammatory lipid mediators.
AB  - PGs and leukotrienes (LTs) mediate cardinal signs of inflammation; hence, their
      enzymes are targets of current anti-inflammatory therapies. Products of
      arachidonate 15-lipoxygenases (LO) types I and II display both beneficial roles,
      such as lipoxins (LXs) that stereoselectively signal counterregulation, as well
      as potential deleterious actions (i.e., nonspecific phospholipid degradation). In
      this study, we examined transgenic (TG) rabbits overexpressing 15-LO type I and
      their response to inflammatory challenge. Skin challenges with either LTB(4) or
      IL-8 showed that 15-LO TG rabbits give markedly reduced neutrophil (PMN)
      recruitment and plasma leakage at dermal sites with LTB(4). PMN from TG rabbits
      also exhibited a dramatic reduction in LTB(4)-stimulated granular mobilization
      that was not evident with peptide chemoattractants. Leukocytes from 15-LO TG
      rabbits gave enhanced LX production, underscoring differences in lipid mediator
      profiles compared with non-TG rabbits. Microbe-associated inflammation and
      leukocyte-mediated bone destruction were assessed by initiating acute
      periodontitis. 15-LO TG rabbits exhibited markedly reduced bone loss and local
      inflammation. Because enhanced LX production was associated with an increased
      anti-inflammatory status of 15-LO TG rabbits, a stable analog of 5S,6R,15S
      trihydroxyeicosa-7E,9E,11Z,13E-tetraenoic acid (LXA(4)) was applied to the
      gingival crevice subject to periodontitis. Topical application with the 15-epi-16
      phenoxy-para-fluoro-LXA(4) stable analog (ATLa) dramatically reduced leukocyte
      infiltration, ensuing bone loss as well as inflammation. These results indicate
      that overexpression of 15-LO type I and LXA(4) is associated with dampened PMN
      mediated tissue degradation and bone loss, suggesting that enhanced anti
      inflammation status is an active process. Moreover, they suggest that LXs can be
      targets for novel approaches to diseases, e.g., periodontitis and arthritis,
      where inflammation and bone destruction are features.

PMID- 14662893
TI  - IL-12 p40 homodimer-dependent macrophage chemotaxis and respiratory viral
      inflammation are mediated through IL-12 receptor beta 1.
AB  - Leukocyte recruitment to the airway lumen is a central feature of inflammatory
      conditions such as asthma and respiratory viral infection. Characterization of
      mediators that regulate leukocyte recruitment in these conditions revealed
      increased IL-12 p40 homodimer (p80) levels were associated with enhanced airway
      macrophage accumulation. To examine this association, we used in vivo and in
      vitro assays to demonstrate p80, but not IL-12 or p40, provided a macrophage
      chemoattractant signal. Macrophages from genetically deficient mice indicated p80
      dependent chemotaxis was independent of IL-12 and required IL-12Rbeta1 (Rbeta1)
      expression. Furthermore, analysis of murine cell lines and primary culture
      macrophages revealed Rbeta1 expression, with an intact cytoplasmic tail, was
      necessary and sufficient to mediate p80-dependent chemotaxis. To examine the role
      for Rbeta1 in mediating macrophage accumulation in vivo, we contrasted Sendai
      virus-driven airway inflammation in wild-type and Rbeta1-deficient mice. Despite
      similar viral burden and production of the macrophage chemoattractant p80, the
      Rbeta1-deficient mice displayed a selective decrease in airway macrophage
      accumulation and resistance to viral-dependent mortality. Thus, Rbeta1 mediates
      p80-dependent macrophage chemotaxis and inhibition of the p80-Rbeta1 interaction
      may provide a novel anti-inflammatory strategy to manipulate the inflammation
      associated with asthma and respiratory viral infection.

PMID- 14662894
TI  - Adenovirus-transduced dendritic cells injected into skin or lymph node prime
      potent simian immunodeficiency virus-specific T cell immunity in monkeys.
AB  - Adenoviral vectors can be used to deliver complex Ag to dendritic cells (DC), and
      thus may be ideal for stimulating broad T cell responses to viral pathogens and
      tumors. To test this hypothesis in a relevant primate model, we used recombinant
      adenovirus serotype 5 vectors expressing SIV Gag Ag to transduce monocyte-derived
      DC from rhesus macaques, and then immunized donor animals either by intradermal
      or intranodal injections. T cell responses were evaluated by ELISPOT assay using
      previously frozen PBMC pulsed with pools of 15-mer peptides representing the Gag
      sequence. Immunization resulted in rapid and potent induction of T cell responses
      to multiple regions of Gag, with frequencies approaching 1 Gag-specific T cell
      per 500 uncultured PBMC. Surprisingly, intradermal and intranodal injections
      generated a similar intensity and breadth of response, indicating that
      administration of Ag-expressing DC by either route may be equally effective at
      inducing immune responses. Detailed analysis of two monkeys revealed CD8(+) T
      cell responses to several peptide epitopes of Gag not previously described, at
      least two of which are restricted by MHC class I alleles not currently
      identified. Repeated vaccination did not induce T cell responses to the
      adenoviral vector and did not prevent Ag-expressing DC injected under the capsule
      of the lymph node from migrating to the paracortex and interposing between T
      cells. However, boost injections of adenovirus-transduced DC were generally
      limited in efficacy. These findings support the use of adenovirus-transduced DC
      in the therapy of HIV infection and cancer.

PMID- 14662895
TI  - A novel protein highly expressed in testis is overexpressed in systemic sclerosis
      fibroblasts and targeted by autoantibodies.
AB  - Nearly all autoantibody specificities in sera from patients with systemic
      sclerosis (SSc) target proteins distributed ubiquitously, and Abs against
      proteins whose expression is restricted to the affected sites have not been
      identified. In this study we describe SSc-specific autoantibody to a novel
      testicular Ag, termed protein highly expressed in testis (PHET), which is
      ectopically overexpressed in SSc dermal fibroblasts. A partial cDNA encoding PHET
      was isolated by immunoscreening of a HepG2 cDNA library with an SSc serum. PHET
      appeared to be a member of the UniGene cluster Hs.129872, but had a unique exon
      composition and a characteristic mRNA expression profile restricted to the
      testis. Serum Abs to a recombinant PHET fragment were detected in nine (8.4%) of
      107 SSc patients, but in none of 50 systemic lupus erythematosus patients or 77
      healthy controls. In SSc patients, the presence of anti-PHET Abs was associated
      with diffuse cutaneous SSc and lung involvement (p = 0.02 and 0.01,
      respectively). PCR-based quantitative analysis of PHET mRNA expression in
      cultured dermal fibroblasts showed increased expression of PHET mRNA in SSc
      fibroblasts compared with control fibroblasts. PHET-reactive Abs purified from
      SSc sera stained the cytoplasm of SSc dermal fibroblasts, and the staining
      intensity tended to be more prominent on SSc compared with control fibroblasts.
      These findings suggest that the autoantibody response to PHET can be induced by
      ectopic overexpression of PHET in dermal fibroblasts in SSc patients.

PMID- 14662896
TI  - Evasion from NK cell immunity by MHC class I chain-related molecules expressing
      colon adenocarcinoma.
AB  - Evasion of host immune responses is well documented for viruses and may also
      occur during tumor immunosurveillance. The mechanisms involve alterations in MHC
      class I expression, Ag processing and presentation, chemokine and cytokine
      production, and lymphocyte receptor expression. Epithelial tumors overexpress MHC
      class I chain-related (MIC) molecules, which are ligands for the activating
      receptor NKG2D on NK and T cells. We report that NK cells from patients with
      colorectal cancer lack expression of activating NKG2D and chemokine CXCR1
      receptors, both of which are internalized. Serum levels of soluble MIC (sMIC) are
      elevated and are responsible for down-modulation of NKG2D and CXCR1. In contrast,
      high serum levels of CXC ligands, IL-8, and epithelial-neutrophil-activating
      peptide (ENA-78) do not down-modulate CXCR1. In vitro, internalization of NKG2D
      and CXCR1 occurs within 4 and 24 h, respectively, of incubating normal NK cells
      with sMIC-containing serum. Furthermore, natural cytotoxicity receptor NKp44 and
      chemokine receptor CCR7 are also down-modulated in IL-2-activated NK cells
      cocultured in MIC-containing serum-an effect secondary to the down-modulation of
      NKG2D and not directly caused by physical association with sMIC. The patients' NK
      cells up-regulate expression of NKG2D, NKp44, CXCR1, and CCR7 when cultured in
      normal serum or anti-MIC Ab-treated autologous serum. NKG2D(+) but not NKG2D(-)
      NK cells are tumoricidal in vitro, and in vivo they selectively traffic to the
      xenografted carcinoma, form immunological synapse with tumor cells, and
      significantly retard tumor growth in the SCID mice. These results suggest that
      circulating sMIC in the cancer patients deactivates NK immunity by down
      modulating important activating and chemokine receptors.

PMID- 14662897
TI  - Cross-priming of diabetogenic T cells dissociated from CTL-induced shedding of
      beta cell autoantigens.
AB  - Cross-presentation of self Ags by APCs is key to the initiation of organ-specific
      autoimmunity. As MHC class I molecules are essential for the initiation of
      diabetes in nonobese diabetic (NOD) mice, we sought to determine whether the
      initial insult that allows cross-presentation of beta cell autoantigens in
      diabetes is caused by cognate interactions between naive CD8(+) T cells and beta
      cells. Naive splenic CD8(+) T cells from transgenic NOD mice expressing a
      diabetogenic TCR killed peptide-pulsed targets in the absence of APCs. To
      ascertain the role of CD8(+) T cell-induced beta cell lysis in the initiation of
      diabetes, we expressed a rat insulin promoter (RIP)-driven adenovirus E19
      transgene in NOD mice. RIP-E19 expression inhibited MHC class I transport
      exclusively in beta cells and rendered these cells resistant to lysis by CD8(+)
      (but not CD4(+)) T cells, both in vitro and in vivo. Surprisingly, RIP-E19
      expression impaired the accumulation of CD8(+) T cells in islets and delayed the
      onset of islet inflammation, without affecting the timing or magnitude of T cell
      cross-priming in the pancreatic lymph nodes, which is the earliest known event in
      diabetogenesis. These results suggest that access of beta cell autoantigens to
      the cross-presentation pathway in diabetes is T cell independent, and reveal a
      previously unrecognized function of MHC class I molecules on target cells in
      autoimmunity: local retention of disease-initiating clonotypes.

PMID- 14662898
TI  - Influence of MHC class II in susceptibility to beryllium sensitization and
      chronic beryllium disease.
AB  - A glutamic acid at residue 69(Glu(69)) in the HLA-DPB1 gene (Glu(69)) is
      associated with chronic beryllium disease (CBD) and possibly beryllium
      sensitization (BeS). This study tested the hypothesis that MHC class II
      polymorphisms are important in susceptibility to BeS and CBD and that the Glu(69)
      variant is related to markers of disease severity. Genomic DNA was obtained from
      BeS (n = 50), CBD (n = 104), and beryllium-exposed nondiseased (Be-nondiseased)
      (n = 125) subjects. HLA-DPB1, -DRB1, and -DQB1 genotypes were determined by
      (sequence-specific primers) PCR. Disease severity was assessed by pulmonary
      function and exercise testing. A higher frequency of the DPB1 Glu(69) gene was
      found in CBD and BeS compared with the Be-nondiseased subjects, with odds ratios
      of 10.1 for CBD vs Be-nondiseased and 9.5 for BeS vs Be-nondiseased. The majority
      of BeS and CBD subjects displayed non-0201 Glu(69) alleles. Glu(69) homozygosity
      was higher in the CBD subjects, while BeS subjects were intermediate and Be
      nondiseased lowest. DRB1*01 and DQB1*05 phenotypes were reduced in CBD vs Be
      nondiseased subjects, while DRB1*13 and DQB1*06 were associated with CBD in the
      absence of Glu(69). Markers of disease severity, including a lower forced vital
      capacity, diffusion capacity for carbon monoxide, PaO(2) at rest, maximum
      workload on exercise testing, and a higher arterial-alveolar gradient at rest,
      were associated with Glu(69) homozygosity. We conclude that DPB1 Glu69 is a
      marker of sensitization and not specific for disease. Glu(69) homozygosity acts
      as a functional marker associated with markers of CBD severity.

PMID- 14662899
TI  - Trachea allograft class I molecules directly activate and retain CD8+ T cells
      that cause obliterative airways disease.
AB  - Human T cells responding against transplanted allogeneic lung tissue have been
      implicated in late graft failure secondary to obliterative bronchiolitis. This
      obliterative airways disease (OAD) also develops in heterotopic murine tracheal
      allografts in association with graft infiltration by both CD8(+) and CD4(+) T
      cells. To date, there has been little evidence to suggest that directly
      alloreactive CD8(+) T cells either promote chronic rejection or lead to the
      development of OAD following airway allotransplantation. Using L(d)-specific TCR
      Tg 2C CD8(+) T cells adoptively transferred into wild-type B6 (H-2(b)) mice and
      the transplantation of BALB/c (H-2(d)) tracheal allografts, we now show that the
      direct recognition of donor-specific class I MHC molecules by host CD8(+) T cells
      leads to their activation, clonal expansion within the graft, and differentiation
      to an effector phenotype with the capacity to induce airway fibrosis. In
      addition, these experiments demonstrate that ongoing direct alloantigen
      recognition within the transplanted airway tissue is necessary for the
      recruitment and retention of these directly alloreactive CD8(+) T cells. Thus,
      these experiments are the first to definitively show a role for directly
      alloreactive CD8(+) T cells in the chronic rejection that leads to OAD.

PMID- 14662900
TI  - Blocking the monocyte chemoattractant protein-1/CCR2 chemokine pathway induces
      permanent survival of islet allografts through a programmed death-1 ligand-1
      dependent mechanism.
AB  - Islet allografts are subject to rapid rejection through host cellular immune
      responses involving mononuclear cell recruitment and tissue injury. Interruption
      of leukocyte recruitment through chemokine receptor targeting is of therapeutic
      benefit in various experimental models, but little is known about the
      contribution of chemokine pathways to islet allograft rejection. We found that
      murine islets produce monocyte chemoattractant protein-1 (MCP-1; CCL2) in vitro
      and that islet allograft rejection was associated with intragraft expression of
      MCP-1 and its receptor, CCR2. We therefore investigated whether MCP-1 and CCR2
      are required for the rejection of fully MHC-disparate islet allografts. Wild-type
      mice treated with blocking anti-MCP-1 mAb plus a brief, subtherapeutic course of
      rapamycin had long-term islet allograft survival, in contrast to the effect of
      treatment with either mAb or rapamycin alone. CCR2(-/-) mice treated with
      rapamycin also maintained islet allografts long-term. Both MCP/CCR2- and
      rapamycin-sensitive signals were required for maximal proliferation of
      alloreactive T cells, suggesting that MCP-1/CCR2 induce rejection by promoting
      alloreactive T cell clonal expansion and homing and migration. Prolonged islet
      allograft survival achieved by blockade of the MCP-1/CCR2 pathway plus rapamycin
      therapy was accompanied by a mononuclear cell infiltrate expressing the
      inhibitory receptor, programmed death-1 (PD-1), and its ligand (PD-L1, B7-H1),
      and prolongation of islet allograft survival was abrogated by anti-PD-L1 mAb
      therapy. These data show that the blockade of MCP-1 binding to CCR2 in
      conjunction with subtherapeutic immunosuppression can have profound effects on
      islet allograft survival and implicate the expression of the PD-1/PD-L1 pathway
      in the regulation of physiologic responses in vivo.

PMID- 14662901
TI  - Estrogen receptor alpha mediates estrogen's immune protection in autoimmune
      disease.
AB  - Estrogens are known to influence a variety of autoimmune diseases, but it is not
      known whether their actions are mediated through classic estrogen receptor alpha
      (ERalpha). The presence of a functional ER was demonstrated in secondary lymphoid
      tissues, then ERalpha expression was shown at both the RNA and protein levels in
      these tissues. Use of ERalpha knockout mice revealed that both the estrogen
      induced disease protection and the estrogen-induced reduction in proinflammatory
      cytokines were dependent upon ERalpha in the prototypic Th1-mediated autoimmune
      disease experimental autoimmune encephalomyelitis. These findings are central to
      the design of selective ER modifiers which aim to target biologic responses in
      specific organ systems.

PMID- 14662902
TI  - Tumor vaccination after allogeneic bone marrow cell reconstitution of the
      nonmyeloablatively conditioned tumor-bearing murine host.
AB  - Allogeneic bone marrow cell reconstitution of the nonmyeloablatively conditioned
      host is supposed to provide an optimized platform for tumor vaccination. We
      recently showed that an allogeneic T cell-depleted graft was well accepted if the
      tumor-bearing host was NK depleted. Based on this finding, a vaccination protocol
      in tumor-bearing, nonmyeloablatively conditioned, allogeneically reconstituted
      mice was elaborated. Allogeneically reconstituted mice, bearing a renal cell
      carcinoma, received tumor-primed donor lymph node cells (LNC), which had or had
      not matured in the allogeneic host. Primed LNC were supported by tumor lysate
      pulsed dendritic cells, which were donor or host derived. Optimal responses
      against the tumor were observed with host-tolerant, tumor-primed LNC in
      combination with host-derived dendritic cells. High frequencies of tumor-specific
      proliferating and CTLs were recorded; the survival time of tumor-bearing mice was
      significantly prolonged, and in >50% of mice the tumor was completely rejected.
      Notably, severe graft-vs-host disease was observed in reconstituted mice that
      received tumor-primed LNC, which had not matured in the allogeneic host. However,
      graft-vs-host was not aggravated after vaccination with tumor-primed, host
      tolerant LNC. Thus, the LNC were tolerant toward the host, but not toward the
      tumor. The finding convincingly demonstrates the feasibility and efficacy of
      tumor vaccination after allogeneic reconstitution of the nonmyeloablatively
      conditioned host.

PMID- 14662903
TI  - Paradoxical dampening of anti-islet self-reactivity but promotion of diabetes by
      OX40 ligand.
AB  - Costimulatory signals received by diabetogenic T cells during priming by or upon
      secondary encounter with autoantigen are decisive in determining the outcome of
      autoimmune attack. The OX40-OX40 ligand (OX40L) costimulatory pathway is known to
      influence T cell responses, prompting us to examine its role in autoimmune
      diabetes. A null allele at OX40L completely prevented diabetes development in
      nonobese diabetic mice and strongly reduced its incidence in a TCR transgenic
      model (BDC2.5). However, somewhat paradoxically, the initial activation of T
      cells responsive to islet beta cell Ag was slightly faster and more efficient in
      the absence of OX40L, with an increased degree of cell proliferation and survival
      in the deficient hosts. Activated T cell migration into and retention within the
      islets was also slightly accelerated. When challenged in vitro, splenocytes from
      BDC2.5.OX40L(o/o) mice showed no altered reactivity to exogenously added peptide,
      no bias to the Th1 or Th2 phenotype, and no alteration in T cell survival. Thus,
      the OX40/OX40L axis has the paradoxical effect of dampening the early activation
      and migration of autoimmune T cells, but sustains the long-term progression to
      autoimmune destruction.

PMID- 14662904
TI  - Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium
      falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN
      gamma.
AB  - The Plasmodium falciparum circumsporozoite (CS) protein-based pre-erythrocytic
      stage vaccine, RTS,S, induces a high level of protection against experimental
      sporozoite challenge. The immune mechanisms that constitute protection are only
      partially understood, but are presumed to rely on Abs and T cell responses. In
      the present study we compared CS protein peptide-recalled IFN-gamma reactivity of
      pre- and RTS,S-immune lymphocytes from 20 subjects vaccinated with RTS,S. We
      observed elevated IFN-gamma in subjects protected by RTS,S; moreover, both CD4(+)
      and CD8(+) T cells produced IFN-gamma in response to CS protein peptides.
      Significantly, protracted protection, albeit observed only in two of seven
      subjects, was associated with sustained IFN-gamma response. This is the first
      study demonstrating correlation in a controlled Plasmodia sporozoite challenge
      study between protection induced by a recombinant malaria vaccine and Ag-specific
      T cell responses. Field-based malaria vaccine studies are in progress to validate
      the establishment of this cellular response as a possible in vitro correlate of
      protective immunity to exo-erythrocytic stage malaria vaccines.

PMID- 14662905
TI  - Reconstitution of virus-specific CD4 proliferative responses in pediatric HIV-1
      infection.
AB  - Gag-specific CD4 proliferative responses correlate inversely with HIV-1 RNA
      levels in infected adults, and robust responses are characteristic of long-term
      nonprogressive infection. However, strong responses are seldom detected in adult
      subjects with progressive infection and are not generally reconstituted on highly
      active antiretroviral therapy (HAART). To date, the role of HIV-1-specific Th
      responses in children has not been thoroughly examined. We characterized Gag
      specific CD4 responses among 35 perinatally infected subjects, including 2
      children who spontaneously control viremia without antiretroviral therapy, 21
      children with viral loads (VL) of <400 on HAART, and 12 viremic children. Gag
      specific Th activity was assessed by lymphoproliferative assay, and responses
      were mapped using overlapping Gag peptides in an IFN-gamma ELISPOT. Robust
      proliferative responses were detected in the children exhibiting spontaneous
      control of viremia, and mapping of targeted Gag regions in one such subject
      identified multiple epitopes. Among children >or=5 years old, 14 of 17 subjects
      with VL of <400 on HAART demonstrated a significant p24 proliferative response
      (median p24 stimulation index, 20), in contrast with only 1 of 9 viremic children
      (median p24 stimulation index, 2.0; p = 0.0008). However, no subject younger than
      5 years of age possessed a significant response, even when viremia was fully
      suppressed. When compared with adults with VL of <400 on HAART, Th responses
      among children with VL of <400 were both more frequent (p = 0.009) and of greater
      magnitude (p = 0.002). These data suggest that children may have a greater
      intrinsic capacity to reconstitute HIV-1-specific immunity than adults, and may
      be excellent candidates for immune-based therapies.

PMID- 14662906
TI  - Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase
      Blk.
AB  - During B lymphoid ontogeny, assembly of the pre-B cell receptor (BCR) is a
      principal developmental checkpoint at which several Src-related kinases may play
      redundant roles. Here the Src-related kinase Blk is shown to effect functions
      associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused
      proliferation of B progenitor cells and enhanced responsiveness of these cells to
      interleukin 7. In mice lacking a functional pre-BCR, active Blk supported
      maturation beyond the pro-B cell stage, suppressed VH to DJH rearrangement,
      relieved selection for productive heavy chain rearrangement, and stimulated kappa
      rearrangement. These alterations were accompanied by tyrosine phosphorylation of
      immunoglobulin beta and Syk, as well as changes in gene expression consistent
      with developmental maturation. Thus, sustained activation of Blk induces
      responses normally associated with the pre-BCR.

PMID- 14662907
TI  - Interleukin 7 regulates the survival and generation of memory CD4 cells.
AB  - Cytokines, particularly those of the common gamma chain receptor family, provide
      extrinsic signals that regulate naive CD4 cell survival. Whether these cytokines
      are required for the maintenance of memory CD4 cells has not been rigorously
      assessed. In this paper, we examined the contribution of interleukin (IL) 7, a
      constitutively produced common gamma chain receptor cytokine, to the survival of
      resting T cell receptor transgenic memory CD4 cells that were generated in vivo.
      IL-7 mediated the survival and up-regulation of Bcl-2 by resting memory CD4 cells
      in vitro in the absence of proliferation. Memory CD4 cells persisted for extended
      periods upon adoptive transfer into intact or lymphopenic recipients, but not in
      IL-7- mice or in recipients that were rendered deficient in IL-7 by antibody
      blocking. Both central (CD62L+) and effector (CD62L-) memory phenotype CD4 cells
      required IL-7 for survival and, in vivo, memory cells were comparable to naive
      CD4 cells in this regard. Although the generation of primary effector cells from
      naive CD4 cells and their dissemination to nonlymphoid tissues were not affected
      by IL-7 deficiency, memory cells failed to subsequently develop in either the
      lymphoid or nonlymphoid compartments. The results demonstrate that IL-7 can have
      previously unrecognized roles in the maintenance of memory in the CD4 cell
      population and in the survival of CD4 cells with a capacity to become memory
      cells.

PMID- 14662908
TI  - Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune
      inflammation.
AB  - Interleukin (IL) 23 is a heterodimeric cytokine composed of a p19 subunit and the
      p40 subunit of IL-12. IL-23 affects memory T cell and inflammatory macrophage
      function through engagement of a novel receptor (IL-23R) on these cells. Recent
      analysis of the contribution of IL-12 and IL-23 to central nervous system
      autoimmune inflammation demonstrated that IL-23 rather than IL-12 was the
      essential cytokine. Using gene-targeted mice lacking only IL-12 (p35-/-) or IL-23
      (p19-/-), we show that the specific absence of IL-23 is protective, whereas loss
      of IL-12 exacerbates collagen-induced arthritis. IL-23 gene-targeted mice did not
      develop clinical signs of disease and were completely resistant to the
      development of joint and bone pathology. Resistance correlated with an absence of
      IL-17-producing CD4+ T cells despite normal induction of collagen-specific,
      interferon-gamma-producing T helper 1 cells. In contrast, IL-12-deficient p35-/-
      mice developed more IL-17-producing CD4+ T cells, as well as elevated mRNA
      expression of proinflammatory tumor necrosis factor, IL-1beta, IL-6, and IL-17 in
      affected tissues of diseased mice. The data presented here indicate that IL-23 is
      an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12
      paradoxically mediates protection from autoimmune inflammation.

PMID- 14662909
TI  - A critical role for induced IgM in the protection against West Nile virus
      infection.
AB  - In humans, the elderly and immunocompromised are at greatest risk for
      disseminated West Nile virus (WNV) infection, yet the immunologic basis for this
      remains unclear. We demonstrated previously that B cells and IgG contributed to
      the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A.
      Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578-2586). In this paper, we
      addressed the function of IgM in controlling WNV infection. C57BL/6J mice (sIgM-/
      ) that were deficient in the production of secreted IgM but capable of expressing
      surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal
      infection, even after inoculation with low doses of WNV. Within 96 h, markedly
      higher levels of infectious virus were detected in the serum of sIgM-/- mice
      compared with wild-type mice. The enhanced viremia correlated with higher WNV
      burdens in the central nervous system, and was also associated with a blunted
      anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG
      protected sIgM-/- mice against mortality, although administration of comparable
      amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a
      prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly
      predicted mortality in wild-type mice. Thus, the induction of a specific,
      neutralizing IgM response early in the course of WNV infection limits viremia and
      dissemination into the central nervous system, and protects against lethal
      infection.

PMID- 14662910
TI  - Functional heterogeneity of marginal zone B cells revealed by their ability to
      generate both early antibody-forming cells and germinal centers with
      hypermutation and memory in response to a T-dependent antigen.
AB  - Marginal zone (MZ) B cells play a major role in the first-line responses against
      blood-born T-independent bacterial antigens (TI), but the full scope of their
      immune functions is not known. Here we compare the responses of MZ and follicular
      (FO) B cells to a T-dependent antigen (TD), hapten-(4-hydroxy-3
      nitrophenyl)acetyl (NP) coupled to chicken gamma-globulin, in a cell transfer
      system. Consistent with the conventional paradigm, MZ B cells but not FO B cells
      rapidly generated the early burst of NP-specific antibody-forming cells (AFC),
      high levels of IgM Ab, and early IgG with relatively high affinity to NP.
      However, MZ B cells were also capable of forming germinal centers (GCs) albeit
      with a delay, compared with FO B cells. The early AFCs and the GCs originated
      from different MZ precursors, but the MZ- and FO-derived GCs were similar in VH
      gene repertoire, somatic mutation, and production of late AFC and IgG Ab.
      Surprisingly, the MZ but not the FO memory response included IgM Ab. We conclude
      that MZ B cells are heterogeneous, comprising cells for both early AFC response
      and GC/memory pathway against TD antigens.

PMID- 14662912
TI  - Characterization of Salmonella enterica serotype newport isolated from humans and
      food animals.
AB  - Salmonella enterica serotype Newport isolates resistant to at least nine
      antimicrobials (including extended-spectrum cephalosporins), known as serotype
      Newport MDR-AmpC isolates, have been rapidly emerging as pathogens in both
      animals and humans throughout the United States. Resistance to extended-spectrum
      cephalosporins is associated with clinical failures, including death, in patients
      with systemic infections. In this study, 87 Salmonella serotype Newport strains
      were characterized by pulsed-field gel electrophoresis (PFGE) and antimicrobial
      susceptibility testing and examined for the presence of class 1 integrons and
      bla(CMY) genes. Thirty-five PFGE patterns were observed with XbaI, and three of
      these patterns were indistinguishable among isolates from humans and animals.
      Fifty-three (60%) Salmonella serotype Newport isolates were identified as
      serotype Newport MDR-AmpC, including 16 (53%) of 30 human isolates, 27 (93%) of
      29 cattle isolates, 7 (70%) of 10 swine isolates, and 3 (30%) of 10 chicken
      isolates. However, 28 (32%) Salmonella serotype Newport isolates were susceptible
      to all 16 antimicrobials tested. The bla(CMY) gene was present in all serotype
      Newport MDR-AmpC isolates. Furthermore, the plasmid-mediated bla(CMY) gene was
      transferable via conjugation to an Escherichia coli strain. The transconjugant
      showed the MDR-AmpC resistance profile. Thirty-five (40%) of the isolates
      possessed class 1 integrons. Sequence analyses of the integrons showed that they
      contained aadA, which confers resistance to streptomycin, or aadA and dhfr, which
      confer resistance to trimethoprim-sulfamethoxazole. One integron from a swine
      isolate contained the sat-1 gene, which encodes resistance to streptothricin, an
      antimicrobial agent that has never been approved for use in the United States. In
      conclusion, Salmonella serotype Newport MDR-AmpC was commonly identified among
      Salmonella serotype Newport isolates recovered from humans and food animals.
      These findings support the possibility of transmission of this organism to humans
      through the food chain.

PMID- 14662911
TI  - Relevance of commercial amplification methods for direct detection of
      Mycobacterium tuberculosis complex in clinical samples.

PMID- 14662913
TI  - Surge capacity for response to bioterrorism in hospital clinical microbiology
      laboratories.
AB  - Surge capacity is the ability to rapidly mobilize to meet an increased demand.
      While large amounts of federal funding have been allocated to public health
      laboratories, little federal funding has been allocated to hospital microbiology
      laboratories. There are concerns that hospital laboratories may have inadequate
      surge capacities to deal with a significant bioterrorism incident. A workflow
      analysis of a clinical microbiology laboratory that serves an urban medical
      center was performed to identify barriers to surge capacity in the setting of a
      bioterrorism event and to identify solutions to these problems. Barriers include
      a national shortage of trained medical technologists, the inability of clinical
      laboratories to deal with a dramatic increase in the number of blood cultures, a
      delay while manufacturers increase production of critical products and then
      transport and deliver these products to clinical laboratories, and a shortage of
      class II biological safety cabinets. Federal funding could remedy staffing
      shortages by making the salaries of medical technologists comparable to those of
      similarly educated health care professionals and by providing financial
      incentives for students to enroll in clinical laboratory science programs. Blood
      culture bottles, and possibly continuous-monitoring blood culture instruments,
      should be added to the national antibiotic stockpile. Federal support must ensure
      that companies that manufacture essential laboratory supplies are capable of
      rapidly scaling up production. Hospitals must provide increased numbers of
      biological safety cabinets and amounts of space dedicated to clinical
      microbiology laboratories. Laboratories should undertake limited cross-training
      of technologists, ensure that adequate packaging supplies are available, and be
      able to move to a 4-day blood culture protocol.

PMID- 14662914
TI  - Acquisition and duration of vancomycin-resistant enterococcal carriage in
      relation to strain type.
AB  - In May 2000, the first outbreak of vancomycin-resistant Enterococcus faecium
      (VREF) was detected in the University Medical Center Utrecht in the nephrology
      ward. The question arose why some VREF strains spread among hospitalized
      patients, whereas other strains do not. Thirty patients who were found to be
      colonized with VREF between May and November 2000 were included in the study.
      Molecular typing confirmed that 19 of them carried an identical epidemic strain
      which harbored the esp gene while 11 were colonized by nonepidemic strains that
      were all esp negative. Acquisition of the outbreak strain was significantly
      associated with diabetes mellitus, renal transplantation, and extensive use of
      antibiotics, especially cephalosporins, in the 2-month period before the first
      isolation of VREF. To establish the duration of colonization, prospective
      surveillance of VREF carriage for a 6-month period starting from the first
      isolation of VREF was realized for 20 patients. After 6 months, VREF was still
      recovered from 60% of carriers of the outbreak strain versus 20% of carriers of
      nonepidemic strains (P < 0.01). However, antibiotic use during the follow-up
      period was significantly higher by carriers of the outbreak strain than by
      carriers of nonepidemic strains. The fact that the outbreak strain was recovered
      for a longer period of time than nonepidemic strains may facilitate dissemination
      of the strain. The results support a careful restrictive antibiotic policy for
      wards at risk for spread of VREF and implementation of isolation precautions for
      patients who are colonized with esp-positive outbreak strains.

PMID- 14662915
TI  - Growth of Helicobacter pylori in medium supplemented with cyanobacterial extract.
AB  - Solid and liquid media supplemented only with a cyanobacterial extract (CE) and
      free of fetal calf serum (FCS), blood, and its derivatives support the growth of
      Helicobacter pylori. A total of 11 strains of H. pylori isolated from gastric
      biopsy samples were successfully subcultured in Mueller-Hinton agar supplemented
      with 0.4% CE. When this medium was used for primary isolation of H. pylori, a low
      isolation rate (30%) was observed because of the abundant growth of contaminants.
      The growth kinetics of eight isolates and H. pylori reference strain NCTC 11638
      in Mueller-Hinton broth (MHB) supplemented with 0.7% CE were estimated by use of
      growth parameters, and the results were compared with those obtained with MHB-5%
      FCS. For four strains the cellular concentrations obtained with CE were
      statistically higher (P < 0.05) than those obtained with FCS, and in some cases
      these values were similar to the highest values reported in the literature.
      Depending on the strain, the specific growth rates obtained with CE were similar
      to or increased compared with those obtained with FCS. The replacement of FCS by
      CE in H. pylori cultures would facilitate the retrieval of cultures with high
      cellular densities as a source of cellular and extracellular proteins free of
      serum. Also, CE has advantages over conventional supplements, such as easier
      conservation and compliance with the pressing tendency at present to avoid the
      use of products derived from animals.

PMID- 14662916
TI  - Multilocus variable-number tandem repeat analysis distinguishes outbreak and
      sporadic Escherichia coli O157:H7 isolates.
AB  - Escherichia coli O157:H7 is a major cause of food-borne illness in the United
      States. Outbreak detection involves traditional epidemiological methods and
      routine molecular subtyping by pulsed-field gel electrophoresis (PFGE). PFGE is
      labor-intensive, and the results are difficult to analyze and not easily
      transferable between laboratories. Multilocus variable-number tandem repeat
      (VNTR) analysis (MLVA) is a fast, portable method that analyzes multiple VNTR
      loci, which are areas of the bacterial genome that evolve quickly. Eighty
      isolates, including 21 isolates from five epidemiologically well-characterized
      outbreaks from Pennsylvania and Minnesota, were analyzed by PFGE and MLVA.
      Strains in PFGE clusters were defined as strains that differed by less than or
      equal to one band by using XbaI and the confirmatory enzyme SpeI. MLVA was
      performed by comparing the number of tandem repeats at seven loci. From 6 to 30
      alleles were found at the seven loci, resulting in 64 MLVA types among the 80
      isolates. MLVA correctly identified the isolates from all five outbreaks if only
      a single-locus variant was allowed. MLVA differentiated strains with unique PFGE
      types. Additionally, MLVA discriminated strains within PFGE-defined clusters that
      were not known to be part of an outbreak. In addition to being a simple and
      validated method for E. coli O157:H7 outbreak detection, MLVA appears to have a
      sensitivity equal to that of PFGE and a specificity superior to that of PFGE.

PMID- 14662917
TI  - Evolution of sfbI encoding streptococcal fibronectin-binding protein I:
      horizontal genetic transfer and gene mosaic structure.
AB  - Streptococcal fibronectin-binding protein is an important virulence factor
      involved in colonization and invasion of epithelial cells and tissues by
      Streptococcus pyogenes. In order to investigate the mechanisms involved in the
      evolution of sfbI, the sfbI genes from 54 strains were sequenced. Thirty-four
      distinct alleles were identified. Three principal mechanisms appear to have been
      involved in the evolution of sfbI. The amino-terminal aromatic amino acid-rich
      domain is the most variable region and is apparently generated by intergenic
      recombination of horizontally acquired DNA cassettes, resulting in a genetic
      mosaic in this region. Two distinct and divergent sequence types that shared only
      61 to 70% identity were identified in the central proline-rich region, while
      variation at the 3' end of the gene is due to deletion or duplication of defined
      repeat units. Potential antigenic and functional variabilities in SfbI imply
      significant selective pressure in vivo with direct implications for the microbial
      pathogenesis of S. pyogenes.

PMID- 14662918
TI  - PCR typing of genetic determinants for metallo-beta-lactamases and integrases
      carried by gram-negative bacteria isolated in Japan, with focus on the class 3
      integron.
AB  - From January 2001 to December 2002, 587 strains of gram-negative bacterial
      isolates demonstrating resistance to ceftazidime and a combination of sulbactam
      and cefoperazone were subjected to a disk diffusion screening test using sodium
      mercaptoacetic acid; 431 strains (73.4%) appeared to produce metallo-beta
      lactamase (MBL). Of these 431 strains, 357 were found by PCR to carry genes for
      IMP-1 type MBL (bla(IMP-1)), while only 7 and 67 strains carried the IMP-2 gene
      (bla(IMP-2)) and the VIM-2 gene (bla(VIM-2)), respectively. Neither VIM-1 nor SPM
      1 type MBL genes were found among the strains tested. Of 431 strains, 427 carried
      the intI1 gene, and 4 strains carrying both the intI1 and intI3 genes were
      reidentified as Pseudomonas putida harboring bla(IMP-1). Of these four P. putida
      strains, three strains and one strain, respectively, were separately isolated
      from two hospitals located in the same prefecture, and the three strains showed
      very similar pulsed-field gel electrophoresis patterns. Of 357 bla(IMP-1)
      carriers, 116, 53, 51, 47, and 30 strains were identified as Pseudomonas
      aeruginosa, Alcaligenes xylosoxidans, P. putida/fluorescens, Serratia marcescens,
      and Acinetobacter baumannii, respectively. Four strains carrying bla(IMP-2) were
      reidentified as P. putida. Sixty-three P. aeruginosa strains and four P. putida
      strains carried bla(VIM-2). Of 427 intI1-positive strains, 180, 53, 51, 47, and
      35 were identified as P. aeruginosa, A. xylosoxidans, P. putida/fluorescens, S.
      marcescens, and A. baumannii, respectively. In the present study, it was
      confirmed that strains carrying bla(IMP-1) with a class 1 integron are the most
      prevalent type in Japan, although several intI3 carriers have also been
      identified sporadically in this country.

PMID- 14662919
TI  - Use of an immunoglobulin G avidity assay based on recombinant antigens for
      diagnosis of primary Toxoplasma gondii infection during pregnancy.
AB  - The objective of this work was to develop an antibody-specific immunoglobulin G
      (IgG) avidity assay to discriminate between acute and latent phases of Toxoplasma
      gondii infection by using recombinant antigens. One hundred twenty-one serum
      samples from women who developed IgG antibodies against Toxoplasma during
      pregnancy were used. The IgG avidities of antibodies directed against epitopes
      carried by fragments of GRA3, GRA7, MIC3, and SAG1 antigens were measured by
      performing parallel enzyme immunoassays. The avidity index for Toxoplasma
      specific antibodies against a homogeneous mixture of recombinant GRA3, GRA7,
      MIC3, and SAG1 antigens correlated closely with the IgG avidity of antibodies
      against lysed whole-cell T. gondii antigen. The avidity assay performed with the
      recombinant MIC3 antigen highlighted the presence of avidity low-antibodies IgG
      exclusively in sera collected within 2 months after primary infection. The
      presence of T. gondii-specific, low-avidity IgG antibodies against recombinant
      MIC3 antigen can be used to determine the point of infection with T. gondii
      within a 2-month time frame after infection.

PMID- 14662920
TI  - Molecular parameters for precise diagnosis of asymptomatic Epstein-Barr virus
      reactivation in healthy carriers.
AB  - Asymptomatic Epstein-Barr virus (EBV) reactivations periodically occur in oral
      mucosa-associated lymphoid tissues. Until now, EBV reactivation has been
      diagnosed by serologic profiles that suggest virus replication. Serologic
      responses, however, are delayed and do not necessarily indicate ongoing
      replicative activity. The aim of the present study was to establish in healthy
      carriers parameters for a molecular diagnosis of reactivated EBV infection.
      Recent studies emphasized the association of an increase in peripheral-B-cell
      viral load with replicative activity at remote sites. Therefore, real-time PCR
      was used to quantitate EBV genomes in the peripheral blood mononuclear cells
      (PBMC) (viral load) and plasma samples (viremia) of 22 healthy EBV-seropositive
      blood donors over a period of 15 months. Furthermore, transcription of the
      immediate-early gene encoding BZLF1 was investigated in the PBMC of all
      volunteers. Serology suggested reactivation in nine donors, of whom all but one
      showed at least once a significant increase in viral load. Another five
      individuals also exhibited significant changes in viral load but no serologic
      response. Of the 13 volunteers with significant increases in viral load, 6 had a
      period of viremia accompanying the rise in viral load. A stable viral load
      without viremia and negative serology was seen in eight adults. BZLF1 mRNA was
      undetectable throughout. We conclude that for healthy subjects serology
      underestimates the frequency of asymptomatic EBV reactivations. Prospective
      examination of peripheral viral load and viremia is suitable for the exact
      diagnosis of EBV reactivation, which might be of advantage for immunocompromised
      patients in whom EBV reactivations are considerably harmful.

PMID- 14662921
TI  - Changes in gene cassettes of class 1 integrons among Escherichia coli isolates
      from urine specimens collected in Korea during the last two decades.
AB  - Gene cassettes of class 1 integrons in Escherichia coli isolates from urine
      specimens collected in Korea during the last 2 decades were characterized. intI1
      was detected in 54% of the isolates, yet gene cassette regions were amplified in
      only 43% of the isolates. intI2 was detected in 29 (5%) isolates, and no intI3
      was detected in this study. Twenty-one different genes, including genes encoding
      resistance to antibiotics, an alcohol dehydrogenase gene (adhE), and unknown
      genes, were detected. The genes most commonly found in class 1 integrons were
      those for aminoglycoside and trimethoprim resistance. The occurrence of
      aminoglycoside resistance genes in class 1 integrons decreased, and the presence
      of dfr genes increased rapidly, during the last 2 decades. Single-gene cassettes
      were predominant during the 1980s, while multigene cassettes predominated from
      the 1990s on. The aadA1, aadA2, and blaP1-aadA2 gene cassettes were frequently
      found in isolates from the 1980s but were not detected in isolates recovered
      since 2000. dfrA12-aadA2 and dfrA17-aadA5 were the most prevalent gene cassettes
      among isolates recovered from the 1990s on. In conclusion, class 1 integrons
      would appear to be responsible for resistance to antibiotics commonly used to
      treat urinary tract infections, and selection of a specific gene cassette was
      found to occur over the course of time.

PMID- 14662922
TI  - Culture and phenotypic characterization of a Wolbachia pipientis isolate.
AB  - The recent isolation of Wolbachia pipientis in the continuous cell line Aa23,
      established from eggs of a strain of the Asian tiger mosquito Aedes albopictus,
      allowed us to perform extensive characterization of the isolate. Bacterial growth
      could be obtained in C6/36, another A. albopictus cell line, at 28 degrees C and
      in a human embryonic lung fibroblast monolayer at 28 and 37 degrees C, confirming
      that its host cell range is broader than was initially thought. The bacteria were
      best visualized by Diff-Quik and May-Grunwald-Giemsa staining. Proteins from 213
      to 18 kDa with two major protein bands of 65 and 25 kDa were observed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. By Western blotting with
      specific polyclonal mouse and rabbit antisera, dominant immunoreactive antigens
      were found at approximately 100, 80, and 30 kDa. The genome size was calculated
      to be 1,790 +/- 17 kb by pulsed-field gel electrophoresis. The sequence of the
      citrate synthase gene (gltA) of W. pipientis was determined by gene walking. Its
      position in the phylogenetic tree constructed with gltA confirmed that found in a
      phylogenetic tree constructed with 16S rRNA genes and that it belongs in the
      alpha subgroup of the class Proteobacteria and that it is closely related to but
      independent from the genera Ehrlichia, Anaplasma, and Neorickettsia.

PMID- 14662923
TI  - Typing of methicillin-resistant Staphylococcus aureus in a university hospital
      setting by using novel software for spa repeat determination and database
      management.
AB  - The spa gene of Staphylococcus aureus encodes protein A and is used for typing of
      methicillin-resistant Staphylococcus aureus (MRSA). We used sequence typing of
      the spa gene repeat region to study the epidemiology of MRSA at a German
      university hospital. One hundred seven and 84 strains were studied during two
      periods of 10 and 4 months, respectively. Repeats and spa types were determined
      by Ridom StaphType, a novel software tool allowing rapid repeat determination,
      data management and retrieval, and Internet-based assignment of new spa types
      following automatic quality control of DNA sequence chromatograms. Isolates
      representative of the most abundant spa types were subjected to multilocus
      sequence typing and pulsed-field gel electrophoresis. One of two predominant spa
      types was replaced by a clonally related variant in the second study period. Ten
      unique spa types, which were equally distributed in both study periods, were
      recovered. The data show a rapid dynamics of clone circulation in a university
      hospital setting. spa typing was valuable for tracking of epidemic isolates. The
      data show that disproval of epidemiologically suggested transmissions of MRSA is
      one of the main objectives of spa typing in departments with a high incidence of
      MRSA.

PMID- 14662924
TI  - High prevalence of hepatitis B virus pre-s mutant in countries where it is
      endemic and its relationship with genotype and chronicity.
AB  - It has been reported that hepatitis B virus (HBV) mutants carrying mutations in
      the pre-S region can be found in infected patients. In this study, we
      investigated the prevalence of the HBV variant with the pre-S mutant in different
      geographic regions, including countries with low and high levels of endemic HBV
      infection, and analyzed the correlation with clinical findings. We examined 387
      HBV DNA-positive serum samples from individuals among 12 countries, consisting of
      Vietnam, Myanmar, Thailand, China, Korea, Nepal, Japan, Russia, Spain, United
      States, Bolivia, and Ghana. HBV pre-S mutants were detected in 71 (18.3%) of 387
      serum samples tested. This mutant was the most prevalent in Vietnam (36%),
      followed by Nepal (27.3%), Myanmar (23.3%), China (22.4%), Korea (14.3%),
      Thailand (10.5%), Japan (7.7%), and Ghana (4.3%). In contrast, no case with this
      mutation was found in Russia, Spain, United States, and Bolivia. Among the HBV
      deletion mutations, 15.5% (11 of 71) occurred in the pre-S1 and 46.5% (33 of 71)
      in the pre-S2 regions. Eight (11.3%) cases had a mutation in both the pre-S1 and
      pre-S2 regions. In addition, a point mutation at the pre-S2 starting codon was
      observed in 19 (26.7%) cases. The detection rate of the HBV mutant in patients
      with hepatocellular carcinoma was significantly higher than in other patients (P
      < 0.05). Furthermore, these mutants were found more frequently in genotype B
      (25%) and genotype C (24.5%) than in the other genotypes (P < 0.05). Our results
      indicated that there was a high prevalence of HBV pre-S mutation in regions of
      endemic HBV infection in Asia. Furthermore, the pre-S mutation appeared to be
      correlated with hepatocellular carcinoma and HBV genotypes.

PMID- 14662925
TI  - Gene sequence-based criteria for identification of new rickettsia isolates and
      description of Rickettsia heilongjiangensis sp. nov.
AB  - We propose genetic guidelines for the classification of rickettsial isolates at
      the genus, group, and species levels by using sequences of the 16S rRNA (rrs)
      gene and four protein-coding genes, the gltA, ompA, and ompB genes and gene D. To
      be classified as a member of the genus Rickettsia, an isolate should exhibit
      degrees of rrs and gltA homology with any of the 20 Rickettsia species studied of
      >/=98.1 and >/=86.5%, respectively. A member of the typhus group should fulfill
      at least two of the following four criteria: pairwise nucleotide sequence
      homologies with rrs, gltA, ompB, and gene D of either Rickettsia typhi or
      Rickettsia prowazekii of >/=99.4, >/=96.6, >/=92.4, and >/=91.6%, respectively. A
      member of the spotted fever group should either possess the ompA gene or fulfill
      at least two of the following four criteria: pairwise nucleotide sequence
      homologies with rrs, gltA, ompB, and gene D of any member of this group of
      >/=98.8, >/=92.7, >/=85.8, and >/=82.2%, respectively. The existence of a
      distinct "ancestral" group should be questioned. To be classified as a new
      Rickettsia species, an isolate should not exhibit more than one of the following
      degrees of nucleotide similarity with the most homologous validated species:
      >/=99.8 and >/=99.9% for the rrs and gltA genes, respectively, and, when
      amplifiable, >/=98.8, >/=99.2, and >/=99.3% for the ompA and ompB genes and gene
      D, respectively. By use of our classification scheme, "Rickettsia heilongjiangii"
      belongs to a new species for which we officially propose the name Rickettsia
      heilongjiangensis sp. nov.

PMID- 14662926
TI  - Evaluation of a PCR assay for quantitation of Rickettsia rickettsii and closely
      related spotted fever group rickettsiae.
AB  - A spotted fever rickettsia quantitative PCR assay (SQ-PCR) was developed for the
      detection and enumeration of Rickettsia rickettsii and other closely related
      spotted fever group rickettsiae. The assay is based on fluorescence detection of
      SYBR Green dye intercalation in a 154-bp fragment of the rOmpA gene during
      amplification by PCR. As few as 5 copies of the rOmpA gene of R. rickettsii can
      be detected. SQ-PCR is suitable for quantitation of R. rickettsii and 10 other
      genotypes of spotted fever group rickettsiae but not for R. akari, R. australis,
      R. bellii, or typhus group rickettsiae. The sensitivity of SQ-PCR was comparable
      to that of a plaque assay using centrifugation for inoculation. The SQ-PCR assay
      was applied successfully to the characterization of rickettsial stock cultures,
      the replication of rickettsiae in cell culture, the recovery of rickettsial DNA
      following different methods of extraction, and the quantitation of rickettsial
      loads in infected animal tissues, clinical samples, and ticks.

PMID- 14662927
TI  - Evaluation of the INNO-LiPA HBV genotyping assay for determination of hepatitis B
      virus genotype.
AB  - Specific genotypes of hepatitis B virus (HBV) are increasingly recognized for
      their clinical significance and association with particular viral mutations.
      Although many HBV genotyping methods exist, there has been no standardized or
      commercially available method for direct molecular typing of the HBV genome. A
      newly available line probe assay (INNO-LiPA HBV Genotyping assay; Innogenetics
      N.V., Ghent, Belgium) that allows the identification of HBV genotypes A to G was
      assessed by comparison with pre-S1/pre-S2 sequence analysis of the isolates in
      188 serum specimens. All seven genotypes were detected by the line probe assay
      (LiPA), and complete concordance between LiPA and sequence analysis was observed
      for 152 specimens (81%). LiPA was able to detect 19 mixed genotype infections not
      detected by amplicon sequencing, which for the most part were confirmed by
      cloning and sequencing of the pre-S1/pre-S2 amplicon. Four specimens had
      discrepant results between the two methods, and five specimens had indeterminate
      results by LiPA. The HBV DNA in four specimens was unable to be amplified by the
      nested INNO-LiPA HBV DR amplification primers; however, the HBV DNA in six
      specimens unable to be genotyped by sequencing was clearly genotyped by LiPA. The
      INNO-LiPA HBV Genotyping assay appears to be useful for the rapid genotyping of
      HBV, particularly for the sensitive detection of mixed genotype infections.

PMID- 14662928
TI  - Genetic Heterogeneity in the rRNA Gene Locus of Trichophyton tonsurans.
AB  - Trichophyton tonsurans is the major pediatric pathogen in tinea capitis, causing
      disparate disease presentations. Little is known about genetic variation, which
      may ultimately be linked to divergent disease status. This investigation was
      aimed at identifying genetic variants of T. tonsurans by methods that can
      facilitate strain discrimination in population-based studies. Ninety-two isolates
      were acquired from six U.S. microbiology laboratories, and genomic DNA was
      isolated from mature colonies. The nontranscribed spacer (NTS) was amplified by
      PCR, and products from isolates with various amplicon sizes were fully sequenced.
      Nested amplification, targeting a variable internal repeat (VIR) region, allowed
      assignment of variant type by fragment size. Subvariant type was assigned by a
      combination of PCR-restriction fragment length polymorphism-based assays. Five
      variants differing in size (348 to 700 bp) and sequence were identified within
      the VIR region comprised of several large repeats (104, 140, and 194 bp) arranged
      in tandem. Seven single-nucleotide polymorphisms (SNPs) were detected across the
      NTS, with five occurring in the constant regions flanking the VIR region and two
      occurring in the VIR region. Additionally, a 10-bp insertion and a 14-bp deletion
      were identified upstream of the VIR region. The combination of SNPs revealed
      seven haplotype patterns which were stable upon serial passage over 1 year. No
      sequence variations were identified within the internal transcribed spacer
      regions. Unique NTS sequences were utilized to develop a duplex PCR assay that
      discriminated T. tonsurans from other dermatophytes. Of the 92 isolates
      evaluated, this genotyping scheme distinguished 12 distinct strains, providing
      evidence of genetic heterogeneity in T. tonsurans.

PMID- 14662929
TI  - Human herpesvirus 8 load in matched serum and plasma samples of patients with
      AIDS-associated Kaposi's sarcoma.
AB  - Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma [KS]-associated herpesvirus) is
      associated with all forms of KS. HHV-8 DNA load in peripheral blood mononuclear
      cells (PBMCs) of KS patients has been shown to correlate with the clinical stage
      of the disease. Studies have been done to assess the HHV-8 viral load in
      different sample types from KS patients and its clinical relevance. This paper
      describes the design and evaluation of a quantitative real-time (TaqMan) PCR
      assay for routine diagnosis of HHV-8 infection. The linear dynamic range was 5 to
      5 x 10(6) copies of HHV-8 DNA (r(2) > 0.99). The assay is very sensitive,
      specific, and easily reproducible (less than 2% variability) and can be used for
      different clinical samples, such as serum, plasma, and PBMCs. The question of
      which clinical sample, serum or plasma, is preferable for HHV8 DNA testing was
      addressed, using this newly developed real-time PCR assay. From 85 patients with
      diagnosed AIDS-KS, matched plasma and serum samples were collected. Of the 85
      patients tested, 35 were positive for HHV-8 DNA in both plasma and serum (41%), 8
      were positive in serum but not plasma, and 7 had detectable HHV-8 DNA only in
      plasma. The HHV-8 load was similar in both plasma and serum, and no significant
      difference was found. However, more inhibition was seen in the plasma samples
      with the use of a system quality control, seal herpesvirus type 1. Therefore, our
      results suggest that serum is the preferred material for HHV-8 load testing,
      since there is less possible hindrance in the amplification than with plasma.

PMID- 14662930
TI  - Development of a multitarget real-time TaqMan PCR assay for enhanced detection of
      Francisella tularensis in complex specimens.
AB  - Tularemia is the zoonotic disease caused by the gram-negative coccobacillus
      Francisella tularensis. Its wide distribution in the environment poses a
      challenge for understanding the transmission, ecology, and epidemiology of the
      disease. F. tularensis is also considered a potential biological weapon due to
      its extreme infectivity. We have developed a multitarget real-time TaqMan PCR
      assay capable of rapidly and accurately detecting F. tularensis in complex
      specimens. Targeted regions included the ISFtu2 element and the 23kDa, fopA, and
      tul4 genes. Analysis of the four TaqMan assays demonstrated that three (ISFtu2,
      23kDa, and tul4) performed within our established criterion of a detection limit
      of one organism. The combined use of the three assays was highly specific,
      displaying no cross-reactivity with the non-Francisella bacteria tested and
      capable of differentially diagnosing both F. tularensis and Francisella
      philomiragia. When the multitarget TaqMan assay (ISFtu2, 23kDa, and tul4) was
      compared to culturing, using environmentally contaminated specimens, the TaqMan
      PCR assay was significantly more sensitive than culturing (P </= 0.05). The
      sensitive and specific nature of this rapid multitarget TaqMan assay provides a
      valuable new tool that with future evaluations can be used for analyzing clinical
      specimens, field samples during bioterrorism threat assessment, and samples from
      outbreaks and for improving our understanding of the ecology and environmental
      prevalence of F. tularensis.

PMID- 14662931
TI  - Culture-independent identification of pathogenic bacteria and polymicrobial
      infections in the genitourinary tract of renal transplant recipients.
AB  - Renal transplant recipients are predisposed to urinary tract infections caused by
      both common uropathogens and opportunistic bacteria resulting frequently in
      significant polymicrobial infections. In this study, a culture-independent 16S
      rRNA-based approach was established to identify unusual, fastidious, or anaerobic
      bacteria and to investigate bacterial diversity in urinary tract specimens.
      Similarly sized amplicons encompassing the V6 to V8 region of the 16S rRNA were
      analyzed with denaturing high-performance liquid chromatography (DHPLC) (WAVE
      System). Artificial mixtures of single amplicons from commonly encountered
      uropathogenic bacteria produced distinct peak profiles whose identities were
      confirmed by sequencing individually collected peak products. We evaluated the
      application of the method on 109 urinary tract specimens from renal transplant
      recipients; 100% correlation was found for culture-positive specimens, and DHPLC
      generated peak profiles. However, for culture-negative specimens, DHPLC
      facilitated the detection of novel peak profiles. DNA sequencing of these
      individual peaks was used to identify the bacteria involved. Thus, in PCR
      positive but culture-negative samples the method allowed detection of previously
      known uropathogens such as Corynebacterium urealyticum and Gardnerella vaginalis,
      but also unusual agents including Anaerococcus lactolyticus, Bacteroides
      vulgatus, Dialister invisus, Fusobacterium nucleatum, Lactobacillus iners,
      Leptotrichia amnionii, Prevotella buccalis, Prevotella ruminicola, Rahnella
      aquatilis, and Streptococcus intermedius were detected as single pathogens or as
      constituents of polymicrobial infections. The method described is reproducible
      and rapidly and enables both DHPLC-based profiling and sequence-based
      investigation of microbial communities and polymicrobial infections. A detailed
      understanding of infections found in recipients of renal transplants will guide
      antibiotic therapy regimens and provide new perspectives for decreasing the risk
      of graft rejection.

PMID- 14662932
TI  - Natural acquisition of Helicobacter pylori infection in newborn rhesus macaques.
AB  - Helicobacter pylori infection is usually acquired in childhood, but precise
      estimates of the age of acquisition are difficult to obtain in young children.
      Since serial endoscopic biopsies are not feasible in human infants, we examined
      acquisition of H. pylori infection that is known to occur in socially housed
      nonhuman primates. By 12 weeks of age, 8 of 20 newborns (40%) were culture
      positive for H. pylori, and prevalence reached 90% by 1 year of age. Newborns
      from infected dams were more commonly infected than those from uninfected dams,
      particularly during the peripartum period, suggesting that close contact during
      this time may facilitate transmission. Transient infection was uncommon and
      occurred only after the first positive culture. These results suggest that in a
      high-prevalence environment, persistent H. pylori infection may be acquired at an
      earlier age than was previously thought. Since clean, potable water was readily
      available, contamination of water supply is not essential for widespread
      infection at an early age in areas where hygiene is otherwise poor. Furthermore,
      breastfeeding seems to offer little protection, since newborn macaques breastfeed
      during the first year of life and typically are fully weaned only when another
      newborn arrives the following spring.

PMID- 14662933
TI  - Loop-mediated isothermal amplification for detection of African trypanosomes.
AB  - While PCR is a method of choice for the detection of African trypanosomes in both
      humans and animals, the expense of this method negates its use as a diagnostic
      method for the detection of endemic trypanosomiasis in African countries. The
      loop-mediated isothermal amplification (LAMP) reaction is a method that amplifies
      DNA with high specificity, efficiency, and rapidity under isothermal conditions
      with only simple incubators. An added advantage of LAMP over PCR-based methods is
      that DNA amplification can be monitored spectrophotometrically and/or with the
      naked eye without the use of dyes. Here we report our conditions for a highly
      sensitive, specific, and easy diagnostic assay based on LAMP technology for the
      detection of parasites in the Trypanosoma brucei group (including T. brucei
      brucei, T. brucei gambiense, T. brucei rhodesiense, and T. evansi) and T.
      congolense. We show that the sensitivity of the LAMP-based method for detection
      of trypanosomes in vitro is up to 100 times higher than that of PCR-based
      methods. In vivo studies in mice infected with human-infective T. brucei
      gambiense further highlight the potential clinical importance of LAMP as a
      diagnostic tool for the identification of African trypanosomiasis.

PMID- 14662934
TI  - Epidemiology of Aspergillus terreus at a university hospital.
AB  - Invasive fungal infections due to Aspergillus species have become a major cause
      of morbidity and mortality among immunocompromised patients. Aspergillus terreus,
      a less common pathogen, appears to be an emerging cause of infection at our
      institution, the University of Alabama hospital in Birmingham. We therefore
      investigated the epidemiology of A. terreus over the past 6 years by using
      culture data; antifungal susceptibility testing with amphotericin B,
      voriconazole, and itraconazole; and molecular typing with random amplification of
      polymorphic DNA-PCR (RAPD-PCR). During the study period, the percentage of A.
      terreus isolates relative to those of other Aspergillus species significantly
      increased, and A. terreus isolates frequently were resistant to amphotericin B.
      Molecular typing with the RAPD technique was useful in discriminating between
      patient isolates, which showed much strain diversity. Further surveillance of A.
      terreus may better define epidemiology and determine whether this organism is
      becoming more frequent in relation to other Aspergillus species.

PMID- 14662935
TI  - Nosocomial outbreak of infections by Proteus mirabilis that produces extended
      spectrum CTX-M-2 type beta-lactamase.
AB  - Nineteen multidrug-resistant Proteus mirabilis strains were isolated from 19
      patients suffering from infections probably caused by P. mirabilis. These strains
      were recovered from urine or other urogenital specimens of 16 inpatients and
      three outpatients with a hospitalization history in a urology ward of Funabashi
      Medical Center, from July 2001 to August 2002. These strains demonstrated
      resistance to cefotaxime, ceftriaxone, cefpodoxime, and aztreonam, while they
      were highly susceptible to ceftazidime (MIC, </=0.5 micro g/ml). The resistance
      level of these strains to cefotaxime was decreased by the presence of clavulanic
      acid. Therefore, the strains were speculated to produce extended-spectrum class A
      beta-lactamases. These strains were later found to carry bla(CTX-M-2) genes by
      both PCR and sequencing analyses. The profiles of SmaI-digested genomic DNA of 19
      isolates were distinguished into five different clusters by biased sinusoidal
      field gel electrophoresis. Four of them, consisting of 18 isolates, were
      suggested to be a clonal expansion. These findings suggested that a nosocomial
      outbreak of infections by CTX-M-2-producing P. mirabilis had occurred in our
      medical center. Most patients suffered from urogenital malignancies with long
      term catheterization. Cefazolin, cefoperazone-sulbactam, and/or levofloxacin were
      mostly administered to the patients, but these agents seemed ineffective for
      eradication of CTX-M-2 producers. Early recognition and rapid identification of
      colonizing antimicrobial-resistant bacteria, including CTX-M-2-producing P.
      mirabilis, would be the most effective measures to cope with further spread of
      this kind of hazardous microorganism in clinical environments.

PMID- 14662936
TI  - Listeria monocytogenes serotype identification by PCR.
AB  - Serotyping is a universally accepted subtyping method for Listeria monocytogenes.
      Identification of the strain serotype permits differentiation between important
      food-borne strains (1/2a, 1/2b, and 4b) and provides a "gold standard" for
      comparing isolates analyzed in different labs and with different techniques.
      Although an efficient enzyme-linked immunosorbent assay serotyping protocol was
      described recently, identification of PCR serotyping primers would further
      increase the ease and accessibility of this classification system. Serotyping PCR
      primers were designed from variable regions of the L. monocytogenes genome. Three
      primer sets were used in conjunction with a previously described Division III
      primer set in order to classify 122 L. monocytogenes strains into five serotype
      groups [1/2a(3a), 1/2b, 1/2c(3c), 4b(d,e), and 4a/c]. Results of the PCR method
      agreed with those of the conventional slide agglutination method for 97, 100, 94,
      and 91% of strains belonging to serotypes 1/2a, 1/2b, 1/2c, and 4b, respectively.

PMID- 14662937
TI  - Antibiotic-resistant invasive pediatric Streptococcus pneumoniae clones in
      Israel.
AB  - Antibiotic-resistant international clones of Streptococcus pneumoniae are
      increasingly reported in different parts of the world. We investigated the spread
      of these clones through an active surveillance performed at the Israeli
      Streptococcal National Center during 1998 and 1999. Isolates were tested for
      antibiotic susceptibility, serotyped, and genotyped by random amplified
      polymorphic DNA analysis and pulsed-field gel electrophoresis. Of 437 isolates,
      276 (63.4%) were antibiotic resistant and 156 (35%) were penicillin
      nonsusceptible (PNS). The PNS isolates were less frequently encountered in
      southern Israel (27 of 136 [20%]) than in other regions (127 of 301 [42%]). Among
      276 antibiotic-resistant isolates, 43 fingerprint patterns were observed. The
      most common clones were 9V/14-a (19.2%), 5-a (17.8%), and 1-a (10%). The 9V/14-a
      clone was less common, while the 1-a clone was more frequent in the south than in
      other regions. The 5-a clone was more common in Jerusalem than in other regions.
      Among the Jewish and Arab populations the most frequent clones were 9V/14-a (20%)
      and 1-a (25%), respectively. Three international clones, 9V/14-a-Spain(9V)-3, 6B
      a-Spain(6B)-2, and 5-a-Colombia(5)-19, comprised 40% of all antibiotic-resistant
      isolates and 56% of all PNS isolates. The seven-valent conjugate vaccine covers
      58% of the most common clones, all highly PNS clones, and 94% of the multidrug
      resistant clones in Israel, while the nine-valent vaccine covers all of them. The
      most common antibiotic-resistant invasive pediatric S. pneumoniae clones-mainly
      the three international ones-contribute significantly to increases in antibiotic
      resistance. Their geographic distribution varies within the country and between
      the different populations.

PMID- 14662938
TI  - Evaluation of methodology for serotyping invasive and nasopharyngeal isolates of
      Haemophilus influenzae in the ongoing surveillance in Brazil.
AB  - To assess the magnitude of discrepant results obtained by routine Haemophilus
      influenzae serotyping, 258 isolates, collected by the epidemiological
      surveillance system in Brazil from individuals with invasive diseases or
      carriage, were evaluated by two slide agglutination (SlAg) methods: SlAg method
      1, by which strains were initially screened with a serotype b-specific antiserum,
      and SlAg method 2, by which strains were tested against all serotype-specific
      antisera in parallel. Investigators comparing results of the two SlAg methods
      with those obtained by capsule type-specific PCR were blinded to the method used.
      The serotype prevalence rates found by the three methods were significantly
      different, involving discrepancies mainly between serotype b and noncapsulated
      (NC) isolates. For invasive isolates (n = 131), the overall agreement rate
      between SlAg method 1 or 2 and PCR was 68.0 or 88.3%, respectively, whereas for
      colonizing isolates (n = 127) the corresponding rate was 46.5 or 94.2%,
      respectively. SlAg method 2 improved the ascertainment of serotypes over that
      obtained with SlAg method 1, demonstrating good correlation with PCR. Use of the
      polyvalent antiserum as a screening reagent for SlAg for invasive and colonizing
      isolates showed poor discriminatory power, with a sensitivity of 65.8% and a
      specificity of 91.7%. We stress the importance of using a well-standardized SlAg
      methodology and suggest that reference laboratories should utilize PCR routinely
      to confirm SlAg results and to check all nonspecific SlAg reactions and apparent
      NC isolates by SlAg in order to provide reliable data on the prevalence of H.
      influenzae serotypes in the H. influenzae type b vaccine era.

PMID- 14662939
TI  - Quantitative validation of media for transportation and storage of Streptococcus
      pneumoniae.
AB  - The need to design effective Streptococcus pneumoniae vaccines and to monitor
      resistance means that it is essential to have efficient methods to determine
      carriage rates. Two liquid media, consisting of skim milk, glycerol, glucose, and
      tryptone soya broth (STGG) or skim milk, glycerol, and glucose (SGG) alone, were
      evaluated for their ability to maintain pneumococcal viability. Optimal recovery
      of S. pneumoniae was achieved when swabs were transferred to STGG medium prior to
      plating onto blood agar-gentamicin selective plates (22%) compared to 7% when
      plated out directly (P < 0.0001 by Fisher's exact test). Both STGG and SGG media
      are appropriate for the long-term storage of pneumococci and primary swab samples
      at -70 degrees C, with no decrease in viable count observed following repeated
      freeze-thaw cycles. Samples could be stored refrigerated for up to 3 days in
      either STGG or SGG medium with no significant loss of viability. Viability
      decreased progressively in storage at 20 to 30 degrees C, with greater losses of
      viability occurring at the higher temperatures. There were no significant
      differences in viability between isolates in the two media. STGG preserved
      pneumococci significantly better (about twofold) than SGG medium at 21 degrees C
      (P < 0.0001) and 30 degrees C (P < 0.0001). Samples can be stored for 4 and 2.5
      days at 6 to 8 degrees C, 28 and 17 h at 21 degrees C, and 15 and 7 h at 30
      degrees C in STGG and SGG media, respectively. For field studies undertaken in
      resource-limited environments, SGG medium can be prepared by using locally
      available materials. The quantitative data reported in this study will enable
      researchers to plan appropriate transport and storage protocols.

PMID- 14662940
TI  - Evidence of Borrelia lonestari DNA in Amblyomma americanum (Acari: Ixodidae)
      removed from humans.
AB  - We used a nested PCR with Borrelia flagellin gene (flaB) primers and DNA
      sequencing to determine if Borrelia lonestari was present in Amblyomma americanum
      ticks removed from military personnel and sent to the Tick-Borne Disease
      Laboratory of the U.S. Army Center for Health Promotion and Preventive Medicine.
      In our preliminary investigation, we detected Borrelia sequences in 19 of 510 A.
      americanum adults and nymphs from Ft. A. P. Hill, Va. During the 2001 tick
      season, the flaB primers were used to test all A. americanum samples as they were
      received, and 29 of 2,358 A. americanum samples tested individually or in small
      pools were positive. PCRs with 2,146 A. americanum samples in 2002 yielded 26
      more Borrelia-positive samples. The positive ticks in 2001 and 2002 were from
      Arkansas, Delaware, Kansas, Kentucky, Maryland, New Jersey, North Carolina,
      Tennessee, and Virginia. The last positive sample of the 2001 season was a pool
      of larvae. To further investigate larval infection, we collected and tested
      questing A. americanum larvae from Aberdeen Proving Ground, Md.; 4 of 33 pools
      (40 larvae per pool) were positive. Infection of unfed larvae provides evidence
      of the maintenance of B. lonestari by means of transovarial transmission.
      Sequence analysis revealed that the amplicons were identical to sequences of the
      B. lonestari flaB gene in GenBank. Despite the low prevalence of infection, the
      risk of B. lonestari transmission may be magnified because A. americanum is often
      abundant and aggressive, and many tick bite victims receive multiple bites.

PMID- 14662941
TI  - Denaturing high-performance liquid chromatography for detecting and typing
      genital human papillomavirus.
AB  - Human papillomaviruses (HPVs) are important in the development of human cancers,
      including cervical and oral tumors. However, most existing methods for HPV typing
      cannot routinely distinguish among the more than 100 distinct types of HPV or the
      natural HPV intratypic variants that have also been documented. To address this
      problem, we developed a novel method, general primer-denaturing high-performance
      liquid chromatography (GP-dHPLC), for the detection and typing of genital HPV
      using an automated 96-well plate format. GP-dHPLC uses general primer PCR (GP
      PCR) to amplify the viral DNA and then analyzes the GP-PCR products by denaturing
      high-performance liquid chromatography (dHPLC). A number of different primer
      pairs with homology to most known genital HPV types were tested, and the L1C1
      L1C2M pair specific for the L1 region of the viral genome was chosen. A set of
      HPV standard control patterns, consisting of those for HPV types 16, 18, 31, 33,
      39, 45, 51, 52, 56, 58, 59, 6, and 11, was established for genital HPV typing.
      One hundred eighty-six frozen and formalin-fixed cervical cancer tissue samples
      were analyzed for the presence of HPV and the HPV type by this method, and 95.8%
      of them were found to contain HPV DNA. GP-dHPLC accurately discriminated among
      HPV variants that differed by as little as one nucleotide. Several new variants
      of HPV types 16, 18, 39, 45, 52, and 59 were identified. Moreover, multiple HPV
      infections were detected in 26.6% of the samples. Our results indicate that HPV
      typing by GP-dHPLC permits discrimination of common genital HPV types, detection
      of multiple HPV infections, and identification of HPV variants in clinical
      samples.

PMID- 14662942
TI  - Molecular analysis of Cryptococcus neoformans mitochondrial cytochrome b gene
      sequences.
AB  - Mitochondrial cytochrome b genes (cyt b) of 40 strains of Cryptococcus neoformans
      were partially sequenced to determine the genetic relations. With the exception
      of the type strain of C. neoformans var. neoformans, all strains contained
      introns in their sequences. Analysis of 386 bp of coding sequence from each
      strain under investigation revealed a total of 27 (6.99%) variable nucleotide
      sites and categorized isolates of C. neoformans into nine cyt b types. C.
      neoformans var. gattii included cyt b types I to V, and C. neoformans var.
      neoformans comprised types VI to IX. cyt b types were correlated with serotypes.
      All strains with cyt b types I, IV, and V were serotype B. All other strains
      except IFM 5878 (serotype B) with cyt b types II and III were serotype C.
      Serotype D strains had cyt b types VI and IX, and serotype A strains were cyt b
      type VIII. Of four serotype AD strains, one was cyt b type VII and the remaining
      three were type VIII. The phylogenetic tree based on deduced amino acid sequences
      divided the strains only into C. neoformans var. neoformans and C. neoformans
      var. gattii. These results indicate that cyt b sequences are effective for DNA
      typing as well as phylogenetic analysis of C. neoformans.

PMID- 14662943
TI  - Borna disease virus RNA in immunocompromised patients in southwestern France.
AB  - Borna disease virus (BDV) is a neurotropic RNA virus with a wide host range.
      Human infections, although controversial, have been described in Europe, Asia,
      and the United States. The present study investigated the existence of BDV
      infections in immunocompromised human beings, namely, 82 human immunodeficiency
      virus (HIV)-infected and 80 therapeutically immunosuppressed patients. BDV p40
      RNAs were detected in peripheral white blood cells with reverse transcription
      nested PCR and hybridization in, respectively, 11 (13.41%) and 1 (1.25%) of the
      two groups of patients. BDV p24 RNAs were identified in only one of those. BDV
      RNA was detected in the absence of any neuropsychiatrical illness, suggesting
      that BDV infections may occur in asymptomatic carriers. The severity and
      particularity of cellular immunosuppression could explain the significantly
      increased detection of BDV RNA in HIV-infected patients.

PMID- 14662944
TI  - Comparison of antibiotic resistance and serotype composition of carriage and
      invasive pneumococci among Bangladeshi children: implications for treatment
      policy and vaccine formulation.
AB  - The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk
      for invasive pneumococcal diseases, and the evaluation of carriage strains is
      thus often used to inform antibiotic treatment and vaccination strategies for
      these diseases. In this study, the age-specific prevalences, resistance to
      antibiotics, and serotype distributions of 1,340 carriage strains were analyzed
      and compared to 71 pneumococcal strains isolated from the cerebrospinal fluid of
      children under 5 years old with meningitis. Overall, the nasal carriage rate was
      47%. One-fourth (26%) of the infants under 1 month of age and one-half (48%) of
      the infants under 12 months of age were colonized with S. pneumoniae. Rural
      children were colonized earlier than those from urban areas. Approximately one
      fourth and one-half of the cases of pneumococcal meningitis occurred in the first
      3 and 6 months of life, respectively. The respective rates of resistance for
      carriage and meningitis strains to penicillin (7 and 3%), cotrimoxazole (77 and
      69%), and erythromycin (2 and 1%) were similar, whereas chloramphenicol
      resistance was lower among carriage strains (3%) than among meningitis strains
      (15.5%). The predominant serogroups of carriage and invasive isolates were
      variable and widely divergent. Thus, hypothetical 7-, 9-, and 11-valent vaccines,
      based on the predominant carriage strains of the present study, would cover only
      23, 26, and 30%, respectively, of the serotypes causing meningitis. Further,
      currently available 7-, 9-, and 11-valent vaccines would protect against only 26,
      43, and 48%, respectively, of these meningitis cases. In conclusion, while the
      surveillance of carriage strains for resistance to antibiotics appears useful in
      the design of empirical treatment guidelines for invasive pneumococcal disease,
      data on the serotypes of carriage strains have limited value in vaccine
      formulation strategies, particularly for meningitis cases.

PMID- 14662945
TI  - Risk factors associated with Campylobacter jejuni infections in Curacao,
      Netherlands Antilles.
AB  - A steady increase in the incidence of Guillain-Barre syndrome (GBS) with a
      seasonal preponderance, almost exclusively related to Campylobacter jejuni, and a
      rise in the incidence of laboratory-confirmed Campylobacter enteritis have been
      reported from Curacao, Netherlands Antilles. We therefore investigated possible
      risk factors associated with diarrhea due to epidemic C. jejuni. Typing by pulsed
      field gel electrophoresis identified four epidemic clones which accounted for
      almost 60% of the infections. One hundred six cases were included in a case
      control study. Infections with epidemic clones were more frequently observed in
      specific districts in Willemstad, the capital of Curacao. One of these clones
      caused infections during the rainy season only and was associated with the
      presence of a deep well around the house. Two out of three GBS-related C. jejuni
      isolates belonged to an epidemic clone. The observations presented point toward
      water as a possible source of Campylobacter infections.

PMID- 14662946
TI  - Molecular evidence for dissemination of unique Campylobacter jejuni clones in
      Curacao, Netherlands Antilles.
AB  - Campylobacter jejuni isolates (n = 234) associated with gastroenteritis and the
      Guillain-Barre syndrome (GBS) in the island of Curacao, Netherlands Antilles, and
      collected from March 1999 to March 2000 were investigated by a range of molecular
      typing techniques. Data obtained by pulsed-field gel electrophoresis (PFGE),
      amplified fragment length polymorphism (AFLP) analysis, multilocus sequence
      typing (MLST), automated ribotyping, and sequence analysis of the short variable
      region of the flagellin gene (flaA) were analyzed separately and in combination.
      Similar groupings were obtained by all methods, with the data obtained by MLST
      and AFLP analysis exhibiting the highest degree of congruency. MLST identified 29
      sequence types, which were assigned to 10 major clonal complexes. PFGE, AFLP
      analysis, and ribotyping identified 10, 9, and 8 of these clonal groups,
      respectively; however, these three techniques permitted subdivision of the clonal
      groups into more different types. Members of seven clonal groups comprising 107
      isolates were obtained from November 1999 to February 2000, and no distinguishing
      characteristics were identified for two GBS-associated strains. The sequence type
      41 (ST-41), ST-508, and ST-657 clonal complexes and their corresponding AFLP
      types have been rare or absent in the Campylobacter data sets described to date.
      We conclude that several clonal complexes of C. jejuni are associated with human
      disease in Curacao, and some of these have not been reported elsewhere.
      Furthermore, given the observation that C. jejuni-associated diseases appear to
      be more severe from November to February, it can be speculated that this may be
      due to the presence of virulent clones with a limited span of circulation.

PMID- 14662947
TI  - Detection of the hepatitis B virus X protein (HBx) antigen and anti-HBx
      antibodies in cases of human hepatocellular carcinoma.
AB  - Hepatitis B virus X protein (HBx) expressed in Escherichia coli DH5alpha by
      recombinant DNA technology was purified to homogeneity by use of glutathione
      Sepharose beads. Immunological characterization of the recombinant HBx protein
      was performed. Specific binding between the anti-HBx monoclonal antibody and HBx
      protein showed the specificity of the recombinant HBx protein. The intact HBx
      protein of the factor Xa-digested glutathione S-transferase-HBx fusion protein
      was further purified and was used as an antigen for screening the titers of anti
      HBx antibodies in sera. Titers of anti-HBx in sera from 20 patients with
      hepatocellular carcinoma (HCC), 20 patients with chronic hepatitis (CH), and 20
      healthy individuals were evaluated by Western blotting and a quantitative enzyme
      linked immunosorbent assay. The results indicated that 70% of sera from HCC
      patients and 5% of sera from CH patients contained antibodies with significant
      binding to the HBx protein. Western blotting of HBx protein in liver extracts
      from 20 HCC patients was also performed by using the anti-HBx monoclonal
      antibody. Results showed that 85% of HCC patients' liver tissues contained a
      specific HBx protein with the same molecular size as the purified intact HBx.
      Full correlation was found between anti-HBx antibody positivity in serum and HBx
      protein positivity in HCC tissues. The data demonstrated that the etiology of HCC
      is involved with hepatitis B virus (HBV) infection and that HBx in particular
      plays a role in the development of HBV-related HCC.

PMID- 14662948
TI  - Concordance of Helicobacter pylori strains within families.
AB  - Helicobacter pylori infection is typically acquired in early childhood, and a
      predominantly intrafamilial transmission has been postulated. To what extent
      family members share the same strains is poorly documented. Our aim was to
      explore patterns of shared strains within families by using molecular typing.
      Family members of H. pylori-infected 10- to 12-year-old index children identified
      in a school survey were invited to undergo gastroscopy. Bacterial isolates were
      typed with random amplified polymorphic DNA and PCR-restriction fragment length
      polymorphism of the genes ureA-B, glmM, or flaA. The presence or absence of the
      cag pathogenicity island, a bacterial virulence factor, was determined by PCR.
      GelCompar II software, supplemented with visual inspection, was used in the
      cluster analysis. In 39 families, 104 individuals contributed 208 bacterial
      isolates from the antrum and corpus. A large proportion, 29 of 36 (81%) of the
      offspring in a sibship, harbored the same strain as at least one sibling. Mother
      offspring strain concordance was detected in 10 of 18 (56%) of the families. Of
      17 investigated father-offspring relations in eight families, none were strain
      concordant. Spouses were infected with the same strains in 5 of 23 (22%) of the
      couples. Different strains in the antrum and corpus were found in 8 of 104 (8%)
      of the subjects. Our family-based fingerprinting study demonstrates a high
      proportion of shared strains among siblings. Transmission between spouses seems
      to be appreciable. The data support mother-child and sib-sib transmission as the
      primary transmission pathways of H. pylori.

PMID- 14662949
TI  - Persistence of two genotypes of Neisseria gonorrhoeae during transmission.
AB  - Isolates of Neisseria gonorrhoeae were tested using a highly discriminatory
      typing method, opa typing, to examine the genetic diversity over a 2-year study
      period of isolates from all consecutive patients with gonorrhea attending the
      Genitourinary Medicine clinic in Sheffield, United Kingdom. Two opa genotypes
      were detected throughout the 2-year time period and comprised 41% of all strains
      tested. The persistence of two opa types was investigated further to determine
      the apparent genetic stability, by examining the ability of isolates to undergo
      intragenic and intergenic recombination and mutation in vitro. Intragenic
      recombination or mutation involving the opa genes of N. gonorrhoeae in the
      selected isolates was not detected, but intergenic recombination did occur. opa
      genes of N. gonorrhoeae in vivo appear to diversify primarily through intergenic
      recombination. Intergenic recombination in vivo would require the presence of a
      mixed gonococcal infection, in which an individual is concurrently colonized with
      more than one strain of N. gonorrhoeae. We propose that the level of diversity of
      opa genotypes in a population is linked to the degree of sexual mixing of
      individuals and the incidence of mixed infections of N. gonorrhoeae.

PMID- 14662950
TI  - Association of the presence of Helicobacter in gallbladder tissue with
      cholelithiasis and cholecystitis.
AB  - The presence of Helicobacter DNA species has been investigated in the biliary
      epithelium of patients with biliary diseases. However, conflicting results have
      been observed that may have been due to the small number of subjects studied,
      difficulty in obtaining a healthy control group, absence of controlling for
      confounding factors, or differences among populations. Therefore, we investigated
      the presence of Helicobacter species by culture and nested PCR of 16S rRNA genes
      in gallbladder tissue and bile from 46 Brazilian subjects with and 18 without
      cholelithiasis. The control group was mainly composed of liver donors and of
      patients who had submitted to cholecystectomy as part of the surgical treatment
      for morbid obesity. No Helicobacter species were grown from the bile or
      gallbladder tissues. Helicobacter DNA was detected in the gallbladder tissue and
      bile from 31.3 and 42.9% of the patients, respectively. In a logistic regression
      model, cholelithiasis was positively and independently associated with the female
      gender (P = 0.02), increasing age (P = 0.002), and the presence of Helicobacter
      DNA in the gallbladder tissue (P = 0.009). The presence of Helicobacter DNA in
      the bile was not associated with cholelithiasis (P = 0.8). A significant
      association between the presence of Helicobacter DNA in the gallbladder
      epithelium and histological cholecystitis, even after adjusting for gender and
      age (P = 0.002), was also observed. The sequences of the 16S rRNA genes were >99%
      similar to that of Helicobacter pylori. In conclusion, our results support the
      hypothesis that Helicobacter is associated with the pathogenesis of human
      cholelithiasis and cholecystitis.

PMID- 14662951
TI  - Use of the Roche LightCycler instrument in a real-time PCR for Trichomonas
      vaginalis in urine samples from females and males.
AB  - Trichomonas vaginalis is the agent of a highly prevalent sexually transmitted
      infection (STI) that can result in vaginitis, urethritis, and preterm birth.
      Traditional methods of diagnosis, including wet preparation, can be unreliable.
      In this study, we describe the adaptation of an existing PCR method for specific
      detection of T. vaginalis DNA into a rapid real-time PCR assay based on
      fluorescence resonance energy transfer (FRET) probe chemistry. The FRET-based
      assay described demonstrated high sensitivity with a detection limit of 1.06
      organisms, as well as a high specificity. A total of 253 urine samples collected
      prospectively from both men and women were tested for T. vaginalis DNA with both
      the FRET-based assay and a previously validated PCR assay. When the validated PCR
      assay was used as the "gold standard" and after discrepancies had been resolved,
      our FRET-based assay demonstrated an analytical sensitivity and specificity of
      90.1 and 100%, respectively. Overall results suggest that FRET-based assays can
      provide rapid, accurate, and high-throughput detection of T. vaginalis and may
      prove useful in clinical settings and for large-scale screening programs.

PMID- 14662952
TI  - Comparison of the susceptibilities of Candida spp. to fluconazole and
      voriconazole in a 4-year global evaluation using disk diffusion.
AB  - From June 1997 to December 2001, results of in vitro susceptibility tests of
      yeast isolates from 35 countries were collected. For 2001 alone, fluconazole
      results were reported for 22,111 yeast isolates from 77 institutions in 30
      countries. Of these isolates, 18,569 were also tested for susceptibility to
      voriconazole. All study sites tested clinical yeast isolates by recently endorsed
      NCCLS disk diffusion method M44-P. Disk test plates were automatically read and
      results were recorded with the BIOMIC Image Analysis System. Species, drug, zone
      diameter, susceptibility category, MIC, and quality control results were
      electronically submitted by e-mail quarterly for analysis. Duplicate test results
      (same patient and same species with same sensitivity-resistance profile and
      biotype results during any 7-day period) and uncontrolled test results were
      eliminated from this analysis. The proportion of Candida albicans isolates
      decreased from 69.7% in 1997 to 1998 to 63.0% in 2001, and this decrease was
      accompanied by a concomitant increase in C. tropicalis and C. parapsilosis. The
      susceptibility (susceptible [S]or susceptible-dose dependent [S-DD]) of C.
      albicans isolates to fluconazole was virtually unchanged, from 99.2% in 1997 to
      99% in 2001; the C. glabrata response to fluconazole was unchanged, from 81.5% S
      or S-DD in 1997 to 81.7% in 2001, although the percentage of resistant isolates
      from blood and upper respiratory tract samples appeared to increase over the
      study period; the percentage of S C. parapsilosis isolates decreased slightly,
      from 98% S or S-DD in 1997 to 96% in 2001; and the percentage of S isolates of C.
      tropicalis increased slightly, from 95.7% in 1997 to 96.9% in 2001. The highest
      rate of resistance to fluconazole among C. albicans isolates was noted in Ecuador
      (7.6%, n = 250). Results from this investigation indicate that the susceptibility
      of yeast isolates to fluconazole has changed minimally worldwide over the 4.5
      year study period and that voriconazole demonstrated 10- to 100-fold greater in
      vitro activity than fluconazole against most yeast species.

PMID- 14662953
TI  - Molecular epidemiology of penicillin-susceptible non-beta-lactam-resistant
      Streptococcus pneumoniae isolates from Greek children.
AB  - A total of 128 Streptococcus pneumoniae isolates that were susceptible to
      penicillin but resistant to non-beta-lactam agents were isolated from young
      carriers in Greece and analyzed by antibiotic susceptibility testing, serotyping,
      restriction fragment end labeling (RFEL), and antibiotic resistance genotyping.
      The serotypes 6A/B (49%), 14 (14%), 19A/F (11%), 11A (9%), 23A/F (4%), 15B/C
      (2%), and 21 (2%) were most prevalent in this collection. Of the isolates, 65%
      were erythromycin resistant, while the remaining isolates were tetracycline
      and/or trimethoprim-sulfamethoxazole resistant. Fifty-nine distinct RFEL types
      were identified. Twenty different RFEL clusters, harboring 2 to 19 strains each,
      accounted for 76% of all strains. Confirmatory multilocus sequence typing
      analysis of the genetic clusters showed the presence of three international
      clones (Tennessee(23F)-4, England(14)-9, and Greece(6B)-22) representing 30% of
      the isolates. The erm(B) gene was present in 70% of the erythromycin-resistant
      isolates, whereas 18 and 8% contained the mef(A) and mef(E) genes, respectively.
      The pneumococci representing erm(B), erm(A), and mef genes belonged to distinct
      genetic clusters. In total, 45% of all isolates were tetracycline resistant.
      Ninety-six percent of these isolates contained the tet(M) gene. In conclusion,
      penicillin-susceptible pneumococci resistant to non-beta-lactams are a
      genetically heterogeneous group displaying a variety of genotypes, resistance
      markers, and serotypes. This suggests that multiple genetic events lead to non
      beta-lactam-resistant pneumococci in Greece. Importantly, most of these genotypes
      are capable of disseminating within the community.

PMID- 14662954
TI  - Use of genetic distance as a measure of ongoing transmission of Mycobacterium
      tuberculosis.
AB  - The stability of the genotypic marker IS6110, used to define the epidemiology of
      Mycobacterium tuberculosis, is one of the most important factors influencing the
      interpretation of DNA fingerprint data. We propose that evolved strains should be
      considered together with clustered strains to represent chains of ongoing
      transmission. For the present study we used a large set of fingerprint data for
      strains collected between 1992 and 1998 from residents of a community with a high
      incidence of tuberculosis in Cape Town, South Africa. Interstrain genetic
      distances were calculated by counting the banding pattern mismatches in the
      IS6110 DNA fingerprints of different isolates. These data demonstrate that the
      propensity to change by one or two bands is independent of the IS6110 copy
      number. Hence, the genetic distance between pairs of isolates can be simply
      expressed as the number of differences in the banding patterns. From this
      foundation, a data set which identifies newly evolved strains has been generated.
      Inclusion of these evolved strains into various molecular epidemiological
      calculations significantly increased the estimate of ongoing transmission in this
      study setting. The indication is that nearly all cases of tuberculosis in this
      community are due to ongoing transmission. This has important implications for
      tuberculosis control, as it indicates that the control measures used at present
      are unable to reduce the level of transmission. This technique may also be
      applicable to the study of low-incidence tuberculosis outbreaks as well as the
      analysis of epidemiological data from other disease epidemics.

PMID- 14662955
TI  - Improved outcomes associated with limiting identification of Candida spp. in
      respiratory secretions.
AB  - Pneumonia due to infection with Candida spp. is extremely rare even though these
      yeasts are commonly cultured from respiratory secretions. The diagnosis of
      pneumonia due to Candida spp. should be made only by demonstrating tissue
      invasion of a biopsy specimen. Physicians might misinterpret the presence of
      Candida spp. in respiratory secretions as being the etiological agent of
      pneumonia. This study describes the practice of limiting identification (ID) of
      rapidly growing yeasts (i.e., Candida spp.) in respiratory secretions and its
      impact on patients. Before November 2001, rapidly growing yeasts found in
      respiratory secretions were identified to the species level. After November,
      rapidly growing yeasts were reported as "yeasts, not Cryptococcus." The group of
      patients with respiratory secretions processed before November 2001 is called the
      full ID group (n = 267); the group with samples processed after that date is
      called the limited ID group (n = 77). Full ID patients had an average length of
      hospital stay of 12.1 days/patient; that of limited ID patients was 10.1
      days/patient, a decrease of 2 days/patient (P = 0.02). The full ID patients had
      an average cost of 9,407 dollars/patient; that of limited ID patients was 6,973
      dollars/patient, a decrease of 2,434 dollars/patient (P = 0.03). Antifungal
      medications were used in 103 of 267 (39%) full ID patients and in 16 of 77 (21%)
      limited ID patients, a decrease of 18% (P = 0.004). Limited ID patients had a
      mortality rate of 14.3%; that of full ID patients was 18.7%, a decrease of 4.4%
      (P = 0.37). This policy of limiting yeast ID did not impair the diagnosis of
      pneumonia. Rather, decreases in lengths of stay, costs, and administration of
      unnecessary antifungal therapy were observed after instituting this policy.

PMID- 14662956
TI  - Characterization of a novel rapidly growing Mycobacterium species associated with
      sepsis.
AB  - A rapidly growing mycobacterium was isolated five times from blood cultures from
      a 6-year-old female patient with relapsed pre-B-cell acute lymphocytic leukemia.
      All five isolates had identical nucleotide sequences for the first 500 bp of the
      16S rRNA gene, indicative of a single species. High-performance liquid
      chromatography analysis of mycolic acids indicated that the species was similar
      to Mycobacterium smegmatis. Sequence analysis of the 16S rRNA gene (1,455 bp) for
      one isolate demonstrated that the species was closely related to Mycobacterium
      diernhoferi. Based on the phenotypic features and phylogenetic analysis, it was
      concluded that the isolates represented a novel rapidly growing Mycobacterium
      species. The name "Mycobacterium hackensackense" is proposed for this unique
      strain, 147-0552(T), which was deposited in the American Type Culture Collection
      as ATCC BAA-823(T).

PMID- 14662957
TI  - Accuracy of six commercially available systems for identification of members of
      the family vibrionaceae.
AB  - Six commercially available bacterial identification products were tested with
      Vibrio alginolyticus (12 strains), V. cholerae (30 strains), Photobacterium
      (Vibrio) damselae (10 strains), V. fluvialis (10 strains), V. furnissii (4
      strains), V. hollisae (10 strains), V. metschnikovii (9 strains), V. mimicus (10
      strains), V. parahaemolyticus (30 strains), and V. vulnificus (10 strains) to
      determine the accuracy of each system for identification. The products included
      API 20E, Crystal E/NF, MicroScan Neg ID2 and Rapid Neg ID3, and Vitek GNI+ and ID
      GNB. Each product was tested only with those species that were listed in its
      database. Overall, the systems correctly identified 63.9, 80.9, 63.1, 73.6, 73.5,
      and 77.7% of the isolates to species level, respectively. Error rates ranged from
      0.8% for the API 20E to 10.4% for the Rapid Neg ID3. The API 20E gave "no
      identification" for 13.1% of the isolates, while the Neg ID2, GNI+, ID-GNB, and
      Crystal were unable to identify 1.8, 2.9, 5.0, and 6.9%, respectively. For V.
      cholerae, specifically, accuracy ranged from 50.0 to 96.7%, with the API 20E
      having the worst performance and Crystal having the best. V. fluvialis presented
      the biggest challenge for the API 20E and the GNI+, with probabilities averaging
      10%, while V. mimicus was a major problem with the Crystal E/NF, which identified
      none of the strains correctly. With the Neg ID2, correct answers were often
      obtained only after a modified inoculation of the panel with a bacterial
      suspension prepared with 0.85% NaCl. Additional tests required for identification
      often included growth in the absence of NaCl, which is not readily available in
      most clinical laboratories. The only product to correctly identify at least 90%
      of V. cholerae strains was the Crystal E/NF, and only three of the six products,
      the API 20E and both of the Vitek cards, correctly identified more than 90% of
      the V. parahaemolyticus strains. Thus, extreme care must be taken in the
      interpretation of answers from these six commercially available systems for the
      identification of Vibrio species.

PMID- 14662958
TI  - Rapid identification of commonly encountered Candida species directly from blood
      culture bottles.
AB  - We report a rapid-cycle, real-time PCR method for identifying six Candida spp.
      directly from BACTEC blood culture bottles. Target sequences in the noncoding
      internal transcribed spacer regions of the rRNA operon were simultaneously
      amplified and interrogated with fluorescent probes to identify Candida albicans,
      C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. lusitaniae; these
      account for 88% of the yeast species isolated from positive blood cultures in our
      laboratory. Any of the first four species can be identified in a single reaction
      using two fluorescent hybridization probe sets. The antifungal-resistant species
      C. krusei and C. lusitaniae are detected in a second reaction, also with two
      probe sets. The assay was validated with DNA extracted from BACTEC blood culture
      bottles positive for yeasts (n = 62) and was 100% concordant with culture
      identification based on biochemical and morphological features of C. albicans (n
      = 22), C. parapsilosis (n = 10), C. tropicalis (n = 1) C. glabrata (n = 22), C.
      krusei (n = 2), and C. lusitaniae (n = 1). No cross-reactivity was observed in
      blood culture samples growing yeasts other than the above-mentioned species (n =
      4), in those growing bacteria (n = 12), or in the absence of microbial growth.
      Our assay allows rapid (</=2 h) and specific detection of the most common Candida
      spp. directly from positive blood cultures and may facilitate delivery of optimal
      antifungal therapy.

PMID- 14662959
TI  - Molecular analysis of the VP7, VP4, VP6, NSP4, and NSP5/6 genes of a buffalo
      rotavirus strain: identification of the rare P[3] rhesus rotavirus-like VP4 gene
      allele.
AB  - We report the detection and molecular characterization of a rotavirus strain,
      10733, isolated from the feces of a buffalo calf affected with diarrhea in Italy.
      Strain 10733 was classified as a P[3] rotavirus, as the VP8* trypsin cleavage
      product of the VP4 protein revealed a high amino acid identity (96.2%) with that
      of rhesus rotavirus strain RRV (P5B[3]), used as the recipient virus in the human
      simian reassortant vaccine. Analysis of the VP7 gene product revealed that strain
      10733 possessed G6 serotype specificity, a type common in ruminants, with an
      amino acid identity to G6 rotavirus strains ranging from 88 to 98%, to Venezuelan
      bovine strain BRV033, and Hungarian human strain Hun4. Phylogenetic analysis
      based on the VP7 gene of G6 rotaviruses identified at least four lineages and an
      apparent linkage between each lineage and the VP4 specificity, suggesting the
      occurrence of repeated interspecies transmissions and genetic reassortment events
      between ruminant and human rotaviruses. Moreover, strain 10733 displayed a bovine
      like NSP4 and NSP5/6 and a subgroup I VP6 specificity, as well as a long
      electropherotype pattern. The detection of the rare P[3] genotype in ruminants
      provides additional evidence for the wide genetic and antigenic diversity of
      group A rotaviruses.

PMID- 14662960
TI  - Development and validation of a quantitative real-time PCR assay using
      fluorescence resonance energy transfer technology for detection of Aspergillus
      fumigatus in experimental invasive pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) is a frequently fatal infection in
      immunocompromised patients that is difficult to diagnose. Present methods for
      detection of Aspergillus spp. in bronchoalveolar lavage (BAL) fluid and in tissue
      vary in sensitivity and specificity. We therefore developed an A. fumigatus
      specific quantitative real-time PCR-based assay utilizing fluorescent resonance
      energy transfer (FRET) technology. We compared the assay to quantitative culture
      of BAL fluid and lung tissue in a rabbit model of experimental IPA. Using an
      enzymatic and high-speed mechanical cell wall disruption protocol, DNA was
      extracted from samples of BAL fluid and lung tissues from noninfected and A.
      fumigatus-infected rabbits. A unique primer set amplified internal transcribed
      spacer regions (ITS) 1 and 2 of the rRNA operon. Amplicon was detected using FRET
      probes targeting a unique region of ITS1. Quantitation of A. fumigatus DNA was
      achieved by use of external standards. The presence of PCR inhibitors was
      determined by use of a unique control plasmid. The analytical sensitivity of the
      assay was </=10 copies of target DNA. No cross-reactivity occurred with other
      medically important filamentous fungi. The assay results correlated with
      pulmonary fungal burden as determined by quantitative culture (r = 0.72, Spearman
      rank correlation; P </= 0.0001). The mean number of genome equivalents detected
      in untreated animals was 3.86 log(10) (range, 0.86 to 6.39 log(10)) in tissue.
      There was a 3.53-log(10) mean reduction of A. fumigatus genome equivalents in
      animals treated with amphotericin B (AMB) (95% confidence interval, 3.38 to 3.69
      log(10); P </= 0.0001), which correlated with the reduction of residual fungal
      burden in lung tissue measured in terms of log(10) CFU/gram. The enhanced
      quantitative sensitivity of the real-time PCR assay was evidenced by detection of
      A. fumigatus genome in infarcted culture-negative lobes, by a greater number of
      mean genome equivalents compared to the number of CFU per gram in tissue and BAL
      fluid, and by superior detection of therapeutic response to AMB in BAL fluid
      compared to culture. This real-time PCR assay using FRET technology is highly
      sensitive and specific in detecting A. fumigatus DNA from BAL fluid and lung
      tissue in experimental IPA.

PMID- 14662961
TI  - New methods to assess susceptibilities of Aspergillus isolates to caspofungin.
AB  - Echinocandins are a group of antifungal agents that target 1,3-beta-glucan
      synthase, causing disruption of mold growth at cells compromising tips and branch
      points. In part because echinocandins do not induce clear growth inhibition end
      points using broth dilution techniques, methods to test susceptibility have not
      yet been standardized. We developed a novel susceptibility assay that measures
      growth of Aspergillus species on solid agar media that contain serial dilutions
      of caspofungin (agar dilution). Results of agar dilution testing of multiple
      isolates were compared to results obtained by broth microdilution (MIC),
      microscopic evaluation (minimal effective concentration [MEC]), and a new method
      to measure fungal burden, quantification of secreted hyphal antigen. MICs
      obtained by the agar dilution method were within 1 dilution of MECs for 85% of
      the Aspergillus isolates; the highest agreement was observed for isolates of
      Aspergillus niger (95%), which were particularly susceptible to caspofungin. Agar
      dilution MICs were also consistent with those obtained by quantifying antigen
      secretion. MICs obtained by broth microdilution were different than MICs by any
      other method. Several Aspergillus isolates with decreased susceptibility to
      caspofungin were identified. Agar dilution is simple and reproducible, and
      results were consistent with the results of more technically demanding
      techniques. This method may be appropriate for use in the clinical laboratory.

PMID- 14662962
TI  - Highly resistant metabolically deficient dwarf mutant of Escherichia coli is the
      cause of a chronic urinary tract infection.
AB  - We present the case of a 68-year-old diabetic woman who has been suffering from
      chronic urinary tract infections, recurring over a period of at least 5 years,
      caused by a slowly growing metabolically deficient dwarf mutant (MDD) of
      Escherichia coli. This MDD strain was auxotrophic for histidine, was resistant to
      multiple antibiotics, and showed atypical growth behavior. Colonies were tiny on
      routine media but were able to revert to normal growth after extended incubation.
      This strain was identified as E. coli by 16S ribosomal DNA sequencing, and
      virulence factor profiles were determined by PCR. Seven MDD isolates collected
      over the 5-year period were grown from midstream urine to significant colony
      counts and shown to belong to the same clonal group by pulsed-field gel
      electrophoresis and enterobacterial repetitive intergenic consensus PCR. These
      MDDs were repeatedly misidentified by biochemical methods due to their slow
      growth and atypical colony morphology. This case highlights the importance of
      recognizing MDDs of Enterobacteriaceae in patients with chronic infections. To
      our knowledge this is the first report of an MDD of E. coli causing a chronic
      urinary tract infection.

PMID- 14662963
TI  - Evaluation of S. aureus ID, a new chromogenic agar medium for detection of
      Staphylococcus aureus.
AB  - S. aureus ID (bioMerieux, La Balme Les Grottes, France) is a new chromogenic agar
      medium designed to enable the isolation of staphylococci and the specific
      identification of Staphylococcus aureus. S. aureus produces green colonies on
      this medium due to production of alpha-glucosidase. To evaluate this medium, a
      total of 350 wound swabs were cultured onto S. aureus ID, CHROMagar Staph.
      aureus, and conventional media routinely used in our laboratory. After 18 to 20 h
      of incubation, 96.8% of strains formed green colonies on S. aureus ID compared
      with 91.1% of strains forming mauve colonies on CHROMagar Staph. aureus. A total
      of 94.3% of strains were recovered within 18 to 20 h with conventional media. The
      sensitivity was increased after 48 h of incubation to 98.7, 96.2, and 95.6% with
      S. aureus ID, CHROMagar Staph. aureus, and conventional media, respectively. A
      total of 97.4% of green colonies on S. aureus ID were confirmed as S. aureus
      compared with 94.4% of mauve colonies on CHROMagar Staph. aureus. We conclude
      that S. aureus ID is a highly sensitive and specific medium for the isolation and
      identification of S. aureus from wound swabs.

PMID- 14662964
TI  - rpoB-based identification of nonpigmented and late-pigmenting rapidly growing
      mycobacteria.
AB  - Nonpigmented and late-pigmenting rapidly growing mycobacteria (RGM) are
      increasingly isolated in clinical microbiology laboratories. Their accurate
      identification remains problematic because classification is labor intensive work
      and because new taxa are not often incorporated into classification databases.
      Also, 16S rRNA gene sequence analysis underestimates RGM diversity and does not
      distinguish between all taxa. We determined the complete nucleotide sequence of
      the rpoB gene, which encodes the bacterial beta subunit of the RNA polymerase,
      for 20 RGM type strains. After using in-house software which analyzes and
      graphically represents variability stretches of 60 bp along the nucleotide
      sequence, our analysis focused on a 723-bp variable region exhibiting 83.9 to 97%
      interspecies similarity and 0 to 1.7% intraspecific divergence. Primer pair Myco
      F-Myco-R was designed as a tool for both PCR amplification and sequencing of this
      region for molecular identification of RGM. This tool was used for identification
      of 63 RGM clinical isolates previously identified at the species level on the
      basis of phenotypic characteristics and by 16S rRNA gene sequence analysis. Of 63
      clinical isolates, 59 (94%) exhibited <2% partial rpoB gene sequence divergence
      from 1 of 20 species under study and were regarded as correctly identified at the
      species level. Mycobacterium abscessus and Mycobacterium mucogenicum isolates
      were clearly distinguished from Mycobacterium chelonae; Mycobacterium mageritense
      isolates were clearly distinguished from "Mycobacterium houstonense." Four
      isolates were not identified at the species level because they exhibited >3%
      partial rpoB gene sequence divergence from the corresponding type strain; they
      belonged to three taxa related to M. mucogenicum, Mycobacterium smegmatis, and
      Mycobacterium porcinum. For M. abscessus and M. mucogenicum, this partial
      sequence yielded a high genetic heterogeneity within the clinical isolates. We
      conclude that molecular identification by analysis of the 723-bp rpoB sequence is
      a rapid and accurate tool for identification of RGM.

PMID- 14662965
TI  - Multilocus sequence typing of Candida glabrata reveals geographically enriched
      clades.
AB  - The haploid pathogenic yeast Candida glabrata is the second most common Candida
      species isolated from cases of bloodstream infection. The clinical relevance of
      C. glabrata is enhanced by its reduced susceptibility to fluconazole. Despite
      this, little is known of the epidemiology or population structure of this
      species. We developed a multilocus sequence typing (MLST) scheme for C. glabrata
      and used it to fingerprint a geographically diverse collection of 107 clinical
      isolates and 2 reference strains. Appropriate loci were identified by amplifying
      and sequencing fragments of the coding regions of 11 C. glabrata genes in 10
      unrelated isolates. The 6 most variable loci (FKS, LEU2, NMT1, TRP1, UGP1, and
      URA3) were sequenced in the collection of 109 isolates. From the 3,345 bp
      sequenced in each isolate, 81 nucleotide sites were found to be variable. These
      defined 30 STs among the 109 strains. The technique was validated by comparison
      with random amplified polymorphic DNA and the complex DNA fingerprinting probes
      Cg6 and Cg12. MLST identified 5 major clades among the isolates studied. Three of
      the clades exhibited significant geographical bias. Our data demonstrate for the
      first time, with such a large geographically diverse strain collection, that
      distinct genetic clades of C. glabrata prevail in different geographical regions.

PMID- 14662966
TI  - Determinants of acquisition and carriage of Staphylococcus aureus in infancy.
AB  - Nasal carriage of Staphylococcus aureus is a major risk factor for invasive S.
      aureus disease. The aim of this study was to define factors associated with
      carriage. We conducted a prospective, longitudinal community-based study of
      infants and their mothers for a period of 6 months following delivery. The
      epidemiology of carriage was examined for 100 infant-mother pairs. Infant
      carriage varied significantly with age, falling from 40 to 50% during the first 8
      weeks to 21% by 6 months. Determinants of infant S. aureus carriage included
      maternal carriage, breastfeeding, and number of siblings. Bacterial typing of S.
      aureus was performed by pulsed-field gel electrophoresis and multilocus sequence
      typing. The majority of individuals carried a single strain of S. aureus over
      time, and the mother was the usual source for colonizing isolates in infants. The
      effect of other components of the normal nasal flora on the development of S.
      aureus carriage was examined in 157 consecutive infants. Negative associations
      (putative bacterial interference) between S. aureus and other species occurred
      early in infancy but were not sustained. An increasing antistaphylococcal effect
      observed over time was not attributable to bacterial interference. S. aureus
      carriage in infants is likely to be determined by a combination of host,
      environmental, and bacterial factors, but bacterial interference does not appear
      to be an ultimate determinant of carrier status.

PMID- 14662967
TI  - New reverse transcription-PCR assay for rapid and sensitive detection of
      enterovirus genomes in cerebrospinal fluid specimens of patients with aseptic
      meningitis.
AB  - Enterovirus (EV) detection by a new commercially available reverse transcription
      (RT)-PCR assay (Penter RT-PCR test) was compared with EV isolation from cell
      cultures and with EV detection by an in-house RT-PCR assay. Of the 54
      cerebrospinal fluid specimens collected during a summer outbreak of aseptic
      meningitis, 52% were positive by cell culture versus 76% by in-house RT-PCR assay
      and 80% by the new RT-PCR test (52 versus 76 versus 80%; P = 0.003). This new
      reliable EV RNA detection test is suitable for clinical diagnosis of EV-related
      meningitis and may improve the management of EV-related neurological syndromes.

PMID- 14662968
TI  - Caspofungin activity against clinical isolates of fluconazole-resistant Candida.
AB  - A total of 7,837 clinical isolates of Candida were tested against fluconazole,
      and 351 resistant (fluconazole MIC >/=64 micro g/ml) isolates were identified (4%
      of the total tested). All fluconazole-resistant isolates were inhibited by
      caspofungin at concentrations that can be exceeded by standard doses (MIC at
      which 90% of the isolates were inhibited, 1 micro g/ml; 99% of the MICs were </=2
      micro g/ml).

PMID- 14662969
TI  - Evaluation of two miniaturized systems, MicroScan W/A and BBL Crystal E/NF, for
      identification of clinical isolates of Aeromonas spp.
AB  - Fifty-two clinical strains and 22 type and reference Aeromonas strains,
      previously genetically characterized by 16S rRNA gene restriction fragment length
      polymorphism, were identified in parallel with the MicroScan Walk/Away and BBL
      Crystal Enteric/Nonfermenter systems. The former identified only 14.8% of the
      isolates correctly, and the latter identified only 20.3% correctly, which
      indicates that neither of these systems is useful for this purpose.

PMID- 14662970
TI  - Comparison of the sequences of the internal transcribed spacer regions and PbGP43
      genes of Paracoccidioides brasiliensis from patients and armadillos (Dasypus
      novemcinctus).
AB  - Paracoccidioides brasiliensis isolates from 10 nine-banded armadillos (Dasypus
      novemcinctus) were comparable with 19 clinical isolates by sequence analysis of
      the PbGP43 gene and ribosomal internal transcribed spacer 1 (ITS1) and ITS2 and
      by random amplified polymorphic DNA. In this original ITS study, eight isolates
      differed by one or three sites among five total substitution sites.

PMID- 14662972
TI  - Pseudomonas cross-infection from cystic fibrosis patients to non-cystic fibrosis
      patients: implications for inpatient care of respiratory patients.
AB  - A 14-year-old boy with bronchiectasis secondary to chronic aspiration developed
      multiresistant Pseudomonas aeruginosa lower respiratory disease following several
      inpatient periods where accommodation and physiotherapy services were shared with
      cystic fibrosis (CF) patients known to be infected with the genetically identical
      strain of P. aeruginosa. Cross-infection with P. aeruginosa between CF patients
      and non-CF patients has not previously been described, and this finding raises
      significant issues relevant to the treatment of patients with non-CF suppurative
      lung disease.

PMID- 14662971
TI  - Most human isolates of Mycobacterium avium Mav-A and Mav-B are strong producers
      of hemolysin, a putative virulence factor.
AB  - Hemolysin was quantified in 58 isolates of Mycobacterium avium from human,
      animal, and environmental sources. Human Mav-A and Mav-B isolates were the
      strongest producers; in contrast, animal and environmental Mav-A isolates and
      human, animal, and environmental Mav-C organisms were low-level producers.
      Hemolysin production was not restricted to isolates causing invasive infections.

PMID- 14662973
TI  - Detection of enterococcal surface protein gene (esp) and amplified fragment
      length polymorphism typing of glycopeptide-resistant Enterococcus faecium during
      its emergence in a Greek intensive care unit.
AB  - The emergence of glycopeptide-resistant Enterococcus faecium (GREF) in a Greek
      intensive care unit was studied by amplified fragment length polymorphism
      analysis and esp gene detection. Three GREF clones harboring the esp gene were
      recovered from 17 out of 21 patients, indicating the dissemination of genetically
      homogenous and virulent strains of GREF.

PMID- 14662974
TI  - DNA fingerprinting of Ralstonia paucula by infrequent-restriction-site PCR and
      randomly amplified polymorphic DNA analysis.
AB  - Ralstonia paucula (formerly CDC group IV c-2) is an environmental organism that
      can cause serious human infections, occasionally clusters of nosocomial
      infections. In the present work, 26 strains of R. paucula (4 from the American
      Centers for Disease Control and Prevention collection, 10 from the Belgian
      Laboratorium voor Microbiologie [LMG] collection, and 12 French clinical
      isolates) were analyzed with infrequent-restriction-site PCR and randomly
      amplified polymorphic DNA analysis. Both techniques accurately distinguished
      between collection strains. Two close patterns obtained for all the French
      isolates suggested a clonal strain. Two LMG collection strains originating from
      human sources in the United States also showed patterns close to those of French
      isolates.

PMID- 14662975
TI  - Molecular comparison of isolates of Burkholderia multivorans from patients with
      cystic fibrosis in the United Kingdom.
AB  - Burkholderia multivorans strains from 47 cystic fibrosis (CF) patients in 28
      hospitals were compared by pulsed-field gel electrophoresis (PFGE) and flagellin
      (fliC) PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. A
      considerable degree of genetic variation was evident, with each patient harboring
      a strain with a unique PFGE profile. Four sizes of fliC amplicons were produced,
      and these amplicons gave 13 RFLP types with restriction enzyme MspI. B.
      multivorans did not appear to spread between patients, suggesting that most CF
      patients acquire the organism from the natural environment.

PMID- 14662976
TI  - Fine-structure molecular typing of Irish Helicobacter pylori isolates and their
      genetic relatedness to strains from four different continents.
AB  - Genotyping of 74 Irish Helicobacter pylori isolates was performed at four
      different loci (vacA signal sequence and mid-region, insertion-deletion
      polymorphisms at the 3' end of the cag pathogenicity island, and cagA). The
      predominant vacA alleles and insertion-deletion motifs suggest an ancestral
      relationship between Irish isolates and either specific East Asian or Northern
      European strains. In addition, fluorescent amplified fragment length polymorphism
      PCR genotyping and phylogenetic analysis of 32 representative Irish H. pylori
      isolates and 22 isolates from four different continents demonstrated that the
      Irish H. pylori isolates examined were weakly clonal and showed some association
      with both European and Asian isolates. These three genotyping techniques show
      that Irish H. pylori isolates have distinctive features that may have evolved in
      this insular European population.

PMID- 14662977
TI  - Evaluation of enzyme-linked immunosorbent assays and a PCR test for detection of
      shiga toxins for shiga toxin-producing Escherichia coli in cattle herds.
AB  - Antigen capture enzyme-linked immunosorbent assays (ELISAs) for the detection of
      Stx1 and/or Stx2 in cattle feces were validated in comparison to the Vero cell
      cytotoxicity neutralization test (as a "gold standard") applied in the course of
      a monitoring program for Shiga toxin-producing Escherichia coli in German cattle
      herds as a prescreening test and compared to MK1/MK2 PCR as an alternative
      prescreening test.

PMID- 14662978
TI  - Serologic and genomic characterization of a G12 human rotavirus in Thailand.
AB  - The G and P type specificity of the human rotavirus strain T-152 (G12P[9])
      isolated in Thailand was serologically confirmed with G12-specific monoclonal
      antibodies prepared in this study by using a reference G12 strain, L26, as an
      immunizing antigen and a P[9]-specific monoclonal antibody, respectively. The
      genomic relationship of strain T-152 with representative human rotavirus strains
      was examined by means of Northern blot analysis. The results showed that T152 is
      closely related to strain AU-1 (G3P[9]). Gene 5 (NSP1 gene) of T152, which did
      not hybridize with those of any other strains examined, was characterized by
      sequence determination. The T152 NSP1 gene is 1,652 nucleotides in length,
      encodes 493 amino acids, and exhibits low identity to those of representative
      human and animal rotaviruses.

PMID- 14662979
TI  - Cocirculation and evolution of two lineages of influenza B viruses in europe and
      Israel in the 2001-2002 season.
AB  - Forty-nine influenza B virus isolates collected in Belgium, Finland, Spain, and
      Israel during the 2001-2002 winter season were categorized into either of two
      lineages, B/Yamagata/16/88 or B/Victoria/2/87, based on the phylogenetic studies
      of HA1 sequences. The data trace the geographic spread of B/Victoria/2/87-like
      viruses and support the emergence of B/Hong Kong/1351/02-like viruses, possibly
      due to selective advantages of reassortment.

PMID- 14662980
TI  - Evaluation of a PCR-based universal heteroduplex generator assay as a tool for
      rapid detection of multidrug-resistant Mycobacterium tuberculosis in Peru.
AB  - Multidrug-resistant tuberculosis is an increasing health problem worldwide,
      especially in developing countries. The PCR-UHG-Rif assay, which detects
      mutations within the rpoB gene associated with rifampin resistance, was evaluated
      for its ability and reliability to detect and identify drug-resistant
      Mycobacterium tuberculosis in a developing country where tuberculosis is highly
      endemic.

PMID- 14662981
TI  - False identification of Coccidioides immitis: do molecular methods always get it
      right?
AB  - rRNA sequence analysis of a partial region of the 18S and 5.8S-internal
      transcribed spacer 2 (ITS2) region of Chrysosporium keratinophilum highlights its
      potential molecular misidentification as Coccidioides immitis. Molecular
      identification of medically important fungi should not be based solely on
      sequence analysis of the 18S rRNA gene but should be confirmed by sequence
      analysis of an additional rRNA gene locus, such as the ITS region(s).

PMID- 14662982
TI  - Diagnosis of severe acute respiratory syndrome (SARS) by detection of SARS
      coronavirus nucleocapsid antibodies in an antigen-capturing enzyme-linked
      immunosorbent assay.
AB  - Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid
      protein was employed to establish an antigen-capturing enzyme-linked
      immunosorbent assay (ELISA). Antinucleocapsid protein antibodies could be
      detected in 68.4% of probable SARS patients 6 to 10 days after illness and in
      89.6% of the patients 11 to 61 days after illness. No false-positive results were
      observed in 20 non-SARS fever patients, 24 non-SARS respiratory illness patients,
      and 20 health care workers. Among 940 other non-SARS clinical serum samples, only
      1 was found to be weakly positive. This method provides a new, sensitive, and
      specific approach for SARS diagnosis.

PMID- 14662983
TI  - First report of capsule replacement among electrophoretic type 37 Neisseria
      meningitidis strains in Italy.
AB  - This report describes the C-to-B capsular switching in four Neisseria
      meningitidis strains belonging to the electrophoretic type 37 (ET-37) complex. In
      particular, one strain belonged to the new sequence type 1860, which was first
      detected in the year 2000 in Italy and is now frequently isolated. The presence
      of switched serogroup B strains deserves special attention if they prove as able
      to spread as their serogroup C progenitors belonging to the hypervirulent ET-37
      complex.

PMID- 14662984
TI  - Dissemination of macrolide-resistant Streptococcus pneumoniae isolates containing
      both erm(B) and mef(A) in South Korea.
AB  - Macrolide resistance was detected in 64 of 77 (83.1%) Streptococcus pneumoniae
      isolates from South Korea. Seven (10.9%) isolates contained only mef(A), 32 (50%)
      contained only erm(B), and 25 (39.1%) contained mef(A) and erm(B). Nineteen
      isolates containing mef(A) and erm(B) belonged to serotype 19F, and seven
      isolates were identical to the Taiwan(19F)-14 clone.

PMID- 14662985
TI  - Expression of plasma coagulase among pathogenic Candida species.
AB  - Candida coagulase production was assessed by the classical tube test. All Candida
      krusei strains were coagulase negative, but most C. albicans and C. tropicalis
      strains can produce coagulase. Some strains agglutinated the Pastorex Staph-Plus
      reagent, probably because of antigen similarities to coagulase produced by
      Staphylococcus aureus that may cause mistakes in clinical laboratories.

PMID- 14662986
TI  - Evaluation of the mandibular third molar pericoronitis flora and its
      susceptibility to different antibiotics prescribed in france.
AB  - This work assessed the polymicrobial flora of mandibular third molar
      pericoronitis. Obligate anaerobes were found in almost all cases (32 of 35).
      Amoxicillin and pristinamycin were the most effective against the flora,
      particularly aerobic organisms. Metronidazole alone or combined with spiramycin
      was the most effective drug against obligate anaerobes.

PMID- 14662987
TI  - Extraintestinal pathogenic Escherichia coli as a cause of invasive nonurinary
      infections.
AB  - Multiple Escherichia coli isolates from four adults with extraintestinal
      infections underwent molecular phylotyping and virulence profiling. A patient
      with secondary peritonitis had two low-virulence E. coli strains from
      phylogenetic groups A and D. In contrast, three patients with invasive
      extraurinary infections (septic arthritis/pyomyositis, nontraumatic
      meningitis/hematogenous osteomyelitis, and pneumonia) each had a single high
      virulence phylogenetic group B2 strain resembling typical isolates causing
      urinary infection and/or sepsis, i.e., extraintestinal pathogenic E. coli.

PMID- 14662989
TI  - Tracheopulmonary myiasis caused by a mature third-instar Cuterebra larva: case
      report and review.
AB  - Myiasis is the infestation of vertebrate tissues with fly larvae (Diptera). Most
      human cases in North America are subcutaneous forms due to Dermatobia hominis
      imported from Central and South America. Human cases of myiasis acquired in North
      America are rare and are primarily subdermal or ophthalmologic forms of
      infestation caused by early stages of Cuterebra larvae. We report an unusual case
      of tracheopulmonary myiasis, resulting from the in situ development of a mature
      cuterebrine larva associated with high eosinophilia. Only two other cases of
      tracheopulmonary cuterebrid myiasis have been reported in humans, and they are
      reviewed herein. Cuterebra myiasis (cuterebrosis) remains a rare and aberrant
      cause of tracheopulmonary disease and is a newly described cause of eosinophilia
      in humans.

PMID- 14662988
TI  - Expression of equi merozoite antigen 2 during development of Babesia equi in the
      midgut and salivary gland of the vector tick Boophilus microplus.
AB  - Equi merozoite antigens 1 and 2 (EMA-1 and EMA-2) are Babesia equi proteins
      expressed on the parasite surface during infection in horses and are orthologues
      of proteins in Theileria spp., which are also tick-transmitted protozoal
      pathogens. We determined in this study whether EMA-1 and EMA-2 were expressed
      within the vector tick Boophilus microplus. B. equi transitions through multiple,
      morphologically distinct stages, including sexual stages, and these transitions
      culminate in the formation of infectious sporozoites in the tick salivary gland.
      EMA-2-positive B. equi stages in the midgut lumen and midgut epithelial cells of
      Boophilus microplus nymphs were identified by reactivity with monoclonal antibody
      36/253.21. This monoclonal antibody also recognized B. equi in salivary glands of
      adult Boophilus microplus. In addition, quantification of B. equi in the
      mammalian host and vector tick indicated that the duration of tick feeding and
      parasitemia levels affected the percentage of nymphs that contained
      morphologically distinct B. equi organisms in the midgut. In contrast, there was
      no conclusive evidence that B. equi EMA-1 was expressed in either the Boophilus
      microplus midgut or salivary gland when monoclonal antibody 36/18.57 was used.
      The expression of B. equi EMA-2 in Boophilus microplus provides a marker for
      detecting the various development stages and facilitates the identification of
      novel stage-specific Babesia proteins for testing transmission-blocking immunity.

PMID- 14662990
TI  - Molecular detection and identification of agents of eumycetoma: detailed report
      of two cases.
AB  - We describe two cases of eumycetoma in the legs. The infections could not be
      adequately diagnosed by classical mycology, but the causative agents were
      successfully identified as Madurella mycetomatis by species-specific PCR and DNA
      sequencing.

PMID- 14662991
TI  - Invasive fungal sinusitis caused by Scytalidium dimidiatum in a lung transplant
      recipient.
AB  - We describe a case of invasive fungal sinusitis caused by Scytalidium dimidiatum
      in a lung transplant recipient. Treatment was complicated by renal failure with
      amphotericin B therapies. Following 6 months of voriconazole treatment, the
      patient remained radiographically and clinically stable for a short time before
      dying of respiratory failure precipitated by graft rejection.

PMID- 14662992
TI  - Salmonella enterica pneumonia in a patient with lung cancer.
AB  - A case of life-threatening Salmonella enterica serotype Enteritidis pneumonia in
      a febrile patient with lung cancer is described. The organism was isolated from
      the sputum, the protected specimen brush material of bronchial secretions, and
      the stool. Despite the early administration of appropriate and adequate
      treatment, the patient died 7 days after the onset of the infection.

PMID- 14662993
TI  - Case of keratitis caused by an uncommon Fusarium species.
AB  - Fusarium polyphialidicum caused a corneal ulcer in a Spanish man. Diagnosis was
      established by a histopathological study and repeated cultures. The isolate was
      clearly resistant in vitro to the antifungal agents tested. This is the first
      case of human or animal mycosis by this rare fungus.

PMID- 14662994
TI  - Trichosporon inkin peritonitis treated with caspofungin.
AB  - Trichosporon inkin is one of six pathogenic species of the genus Trichosporon and
      the etiologic agent of pubic white piedra. Trichosporon species have been
      reported as a cause of disseminated infections, particularly among
      immunosuppressed patients. We describe the third reported case of T. inkin
      peritonitis associated with peritoneal dialysis and the first to be treated with
      caspofungin.

PMID- 14662995
TI  - Fatal case of Salmonella enterica subsp. arizonae gastroenteritis in an infant
      with microcephaly.
AB  - Salmonella enterica subsp. arizonae is a common gut inhabitant of reptiles, with
      snakes as the most common reservoir. Though human cases due to this organism are
      exceedingly rare, it may infect young infants and immunocompromised individuals
      with a history of intimate associations with reptiles. Gastroenteritis is the
      most common presentation; others include peritonitis, pleuritis, osteomyelitis,
      meningitis, and bacteremia. We report a fatal case of S. enterica subsp. arizonae
      gastroenteritis in a 3-month-old child with microcephaly, with a review of
      earlier cases and problems encountered in identification of this rare human
      pathogen.

PMID- 14662996
TI  - Newly emerged multiple-antibiotic-resistant Shigella dysenteriae type 1 strains
      in and around Kolkata, India, are clonal.

PMID- 14662997
TI  - Making internal amplification control mandatory for diagnostic PCR.

PMID- 14662998
TI  - Diarrheagenic potential of Escherichia coli in children in a developed country.

PMID- 14662999
TI  - Latin grammar headaches.

PMID- 14663000
TI  - J. Stephen Fink, MD, PhD (1950-2002).

PMID- 14663001
TI  - Adenosine-dopamine interactions: development of a concept and some comments on
      therapeutic possibilities.
AB  - This brief review presents a personal perspective on the historical development
      of the current knowledge about the biologically important concept of functional
      antagonism between adenosine A2A and dopamine D2 receptors in caudate-putamen,
      accumbens, and tuberculum olfactorium. In the 1970s, studies of dopamine actions
      suggested an unexpected role of adenosine. Developments during the next decade
      substantiated this finding and demonstrated that a subform of adenosine A2
      receptors was enriched in the basal ganglia. Cloning of adenosine receptors
      provided better tools for cellular localization and showed that A2A receptors are
      closely associated with D2 receptors. Distinct functional interactions at several
      levels were discovered, and there is now strong evidence that A2A receptors are
      tonically active and modified by dopamine acting at D2 receptors. Development of
      selective antagonists and knockout mice have highlighted the potential usefulness
      of A2A antagonists in decreasing symptoms and progression of Parkinson's disease
      something that has also been vindicated by careful epidemiologic studies. There
      are issues of efficacy and potential side effects that need to be resolved, but
      the future looks bright.

PMID- 14663002
TI  - Exciting news about A2A receptors.

PMID- 14663003
TI  - Anatomy of adenosine A2A receptors in brain: morphological substrates for
      integration of striatal function.
AB  - A2A adenosine receptors (A(2A)Rs) are expressed with the greatest abundance in
      the striatum and other nuclei of the basal ganglia. The segregated expression of
      A(2A)Rs on the GABAergic striatopallidal medium spiny neurons, where A(2A)R and
      D2 dopamine receptor mRNAs are colocalized, and the opposing functional
      interaction between adenosine and dopamine suggest that A(2A)Rs may be an
      important therapeutic target. To further explore the role of A(2A)Rs in the
      synaptic organization of the basal ganglia, the authors developed an antibody
      directed against the purified A(2A)R. Immunohistochemical studies in rat brain
      showed dense labeling of the neuropil in the striatum, nucleus accumbens, and
      olfactory tubercles with lighter labeling of terminals in the globus pallidus
      (GP), where A(2A)R transcript is not detected. Stimulation of A(2A)Rs on GP
      terminals may facilitate GABAergic signaling and contribute to the overactivation
      observed in Parkinson's disease (PD). Analysis at the ultrastructural level
      allowed a more detailed characterization of the mechanism(s) of A2A-mediated
      control of striatal output. In the striatum, terminals expressing A(2A)Rs
      accounted for 25% of the labeled elements. These presynaptic receptors may
      facilitate excitatory glutamatergic, inhibitory GABAergic, and possibly
      cholinergic striatal transmission. However, the majority of striatal A(2A)R
      immunoreactivity was found on postsynaptic elements, including dendrites of
      striatopallidal neurons, in which A(2A)R and GABA immunoreactivity is
      colocalized. Activation of these receptors may promote GABAergic signaling in
      striatopallidal output neurons and their local axon collaterals in the striatum.
      Many of the A2A-labeled dendrites were contacted by terminals forming asymmetric
      (excitatory) possibly glutamatergic synapses. Using the vesicular glutamate
      transporters (VGLUTs) as markers of glutamatergic terminals, the authors have
      found that VGLUT1-immunoreactive (ir) terminals make asymmetric contacts on A2A
      ir spines and spine heads in the striatum, suggesting that regulation of striatal
      output by A(2A)R stimulation may involve facilitation of the cortical
      glutamatergic excitatory input to striatopallidal neurons. These ultrastructural
      findings suggest several pathways through which A2A receptor blockade may act to
      dampen the elevated striatopallidal GABAergic signaling that occurs in PD.

PMID- 14663005
TI  - A2A receptor and striatal cellular functions: regulation of gene expression,
      currents, and synaptic transmission.
AB  - A2A receptor is highly coexpressed with enkephalin and D2 receptor in
      striatopallidal neurons. A2A antagonists acutely enhance motor behavior in animal
      models of Parkinson's disease (PD) and are therefore considered potential PD
      therapeutic agents. Analysis of gene expression regulation using pharmacologic
      tools or A2A receptor-deficient mice (A2A-/-) shows that the A2A receptor
      positively and tonically controls the expression of enkephalin and immediate
      early genes in striatopallidal neurons. Because this regulation strictly mirrors
      the effect of D2 receptor, these data strongly support the hypothesis that A2A
      antagonists reduce the activity of striatopallidal neurons in models of PD.
      However, analysis of A2A-/- mice suggests additional effects of A2A receptor in
      the control of striatal physiology. Unexpectedly, these animals exhibited a
      reduction in exploratory activity and a 50% reduction in substance P expression.
      This was associated with a 45% decrease in the striatal extracellular dopamine
      concentration, suggesting that chronic absence of A2A receptor results in a
      functional hypodopaminergic state in the striatum. The A2A receptor controls
      inhibitory synaptic transmission negatively in the striatum and positively in the
      globus pallidus; this further supports the efficacy of A2A antagonists in
      reducing the activity of striatopallidal neurons in PD. The A2A receptor does not
      modulate basal alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)
      mediated excitatory corticoaccumbal synaptic transmission during normal
      physiologic conditions. However, genetic inactivation or pharmacologic blockade
      of the A2A receptor significantly reduced long-term potentiation (LTP) at this
      synapse. Therefore, this receptor is implicated in the induction of
      corticoaccumbal LTP, an effect that could be related to its involvement in long
      term behavioral sensitization to repeated dopaminergic treatment.

PMID- 14663004
TI  - Receptor heteromerization in adenosine A2A receptor signaling: relevance for
      striatal function and Parkinson's disease.
AB  - Recently evidence has been presented that adenosine A2A and dopamine D2 receptors
      form functional heteromeric receptor complexes as demonstrated in human
      neuroblastoma cells and mouse fibroblast Ltk- cells. These A2A/D2 heteromeric
      receptor complexes undergo coaggregation, cointernalization, and
      codesensitization on D2 or A2A receptor agonist treatments and especially after
      combined agonist treatment. It is hypothesized that the A2A/D2 receptor heteromer
      represents the molecular basis for the antagonistic A2A/D2 receptor interactions
      demonstrated at the biochemical and behavioral levels. Functional heteromeric
      complexes between A2A and metabotropic glutamate 5 receptors (mGluR5) have also
      recently been demonstrated in HEK-293 cells and rat striatal membrane
      preparations. The A2A/mGluR5 receptor heteromer may account for the synergism
      found after combined agonist treatments demonstrated in different in vitro and in
      vivo models. D2, A2A, and mGluR5 receptors are found together in the dendritic
      spines of the striatopallidal GABA neurons. Therefore, possible D2/A2A/mGluR5
      multimeric receptor complexes and the receptor interactions within them may have
      a major role in controlling the dorsal and ventral striatopallidal GABA neurons
      involved in Parkinson's disease and in schizophrenia and drug addiction,
      respectively.

PMID- 14663006
TI  - Adenosine A2A receptor modulation of motor systems for symptomatic therapy in
      Parkinson's disease.

PMID- 14663007
TI  - A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD.
AB  - The future management of Parkinson's disease (PD) requires pharmacologic agents
      that do not lose efficacy with disease progression or induce dyskinesia and that
      are free of other dopaminergic side effects. A2A receptor antagonists may provide
      an opportunity to introduce nondopaminergic management of PD. A2A receptors are
      selectively localized in basal ganglia and to the indirect output pathway where
      they control GABA and acetylcholine release. The A2A antagonists are effective in
      rodent models of PD, reversing motor deficits in haloperidol-treated, 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated, or reserpinized mice, and
      potentiating L-dopa-induced rotation in 6-hydroxydopamine-lesioned rats without
      inducing dyskinesia. Importantly, the selective A2A antagonist KW6002 reverses
      motor disability and increases locomotor activity in MPTP-treated primates
      without provoking dyskinesia established by previous exposure to L-dopa. In
      addition, KW6002 shows additive antiparkinsonian activity with L-dopa and the D2
      agonist quinpirole in MPTP-treated primates without enhancing the intensity of
      dyskinesia. The data available suggest that A2A antagonists, such as KW6002, may
      be effective as monotherapy for the management of PD and that they will also
      produce additional benefit when administered in combination with L-dopa or
      dopamine agonist therapy.

PMID- 14663008
TI  - Adenosine A2A and dopamine receptor interactions in basal ganglia of dopamine
      denervated rats.
AB  - In the unilateral 6-hydroxydopamine-lesioned rat model of Parkinson's disease,
      blockade of A2A receptors facilitates L-dopa-induced turning behavior by
      antagonism of A2A transmission, which is increased after dopamine depletion.
      After long-term intermittent administration of doses that produced the same
      effect on turning behavior, SCH 58261 (5 mg/kg) + L-dopa (3 mg/kg) induced a
      stable turning behavior, whereas L-dopa (6 mg/kg) alone induced a sensitized
      turning behavior. Behavioral studies were correlated to changes in dynorphin and
      enkephalin mRNAs in the striatum and in glutamic acid decarboxylase 67 (GAD67)
      mRNA in the striatum, globus pallidus, and substantia nigra. The expression of
      dynorphin and, to a lesser extent, enkephalin mRNAs was increased in the lesioned
      striatum of rats that received long-term L-dopa treatment but not in rats that
      received long-term SCH 58261 + L-dopa treatment. Similarly, GAD67 mRNA was
      increased in the striatum and globus pallidus by long-term L-dopa administration
      but not by long-term SCH 58261 + L-dopa administration. GAD67 mRNA was strongly
      reduced in the lesioned substantia nigra after long-term L-dopa treatment,
      whereas the reduction of GAD67 mRNA was less marked after SCH 58261 + L-dopa
      treatment. By increasing L-dopa turning behavior, A2A receptor antagonism allows
      the utilization of doses of L-dopa that do not produce sensitization of turning
      behavior, an effect correlated with the dyskinetic potential of dopamine agonist
      drugs. Moreover, the combination of SCH 58261 + L-dopa produces little or no
      change in the striatal, pallidal, and nigral expression of markers correlated
      with dopamine agonist dyskinetic potential.

PMID- 14663009
TI  - Modulation of GABAergic transmission in the striatopallidal system by adenosine
      A2A receptors: a potential mechanism for the antiparkinsonian effects of A2A
      antagonists.
AB  - The selective localization of adenosine A2A receptors to the striatopallidal
      system suggested a new therapeutic approach to the management of Parkinson's
      disease (PD). The results of behavioral studies using A2A receptor-specific
      agents in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys
      highlight the therapeutic potential of A2A antagonists as a novel treatment for
      PD. However, little is known about the role of A2A receptors in basal ganglia
      function or their pathophysiologic role in PD. Recently, the authors found that
      presynaptic A2A receptors modulate GABAergic synaptic transmission in the
      striatum and globus pallidus (GP), suggesting an A2A receptor-mediated dual
      modulation of the striatopallidal system. Striatal A2A receptors may increase the
      excitability of medium spiny neurons (MSNs) by modulating an intrastriatal
      GABAergic network. In addition, pallidal modulation occurs at striatopallidal MSN
      terminals located at the GP, enhancing GABA release onto GP projection neurons
      and directly suppressing their activity. Blockade of these modulatory functions
      by A2A antagonists could counteract excessive striatopallidal neuronal activity
      provoked by striatal dopamine depletion in patients with PD, leading to a
      reversal of parkinsonian motor deficits.

PMID- 14663010
TI  - A2A receptors in neuroprotection of dopaminergic neurons.

PMID- 14663011
TI  - Caffeinated clues from epidemiology of Parkinson's disease.

PMID- 14663012
TI  - Neuroprotection by caffeine and more specific A2A receptor antagonists in animal
      models of Parkinson's disease.
AB  - A remarkable convergence of epidemiologic and laboratory data has raised the
      possibility that caffeine reduces the risk of developing Parkinson's disease (PD)
      by preventing the degeneration of nigrostriatal dopaminergic neurons. The authors
      review the evidence that caffeine and more specific antagonists of the adenosine
      A2A receptor protect dopaminergic neurons in several toxin models of PD. Other
      studies demonstrating protection by A2A receptor inactivation in animal models of
      stroke, Huntington's disease, and Alzheimer's disease suggest a more global role
      of A2A receptors in neuronal injury and degeneration. Although the cellular and
      molecular mechanisms by which A2A receptors contribute to neuronal death are not
      yet established, several intriguing possibilities have emerged. Now with
      preliminary clinical data substantiating the antiparkinsonian symptomatic benefit
      of A2A receptor blockade, the prospects for a complementary neuroprotective
      benefit have enhanced the therapeutic potential of A2A antagonists in PD.

PMID- 14663013
TI  - Monoamine oxidase B inhibition and neuroprotection: studies on selective
      adenosine A2A receptor antagonists.
AB  - The principal therapeutic agents used in the management of Parkinson's disease
      (PD) enhance nigrostriatal dopaminergic flux through either replenishment of
      depleted dopamine stores or the action of dopaminergic agonists. Adenosine A2A
      receptor antagonists (e.g., KW-6002) may provide symptomatic relief in PD and
      perhaps also may display neuroprotective properties based on studies in the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of nigrostriatal
      neurodegeneration. A second class of compounds that is neuroprotective in the
      MPTP model comprises inhibitors of the outer mitochondrial flavoenzyme monoamine
      oxidase B (MAO B), one of the two forms of MAO that regulate levels of brain
      neurotransmitter substances, including dopamine. In this article, data are
      presented that document the overlapping A2A antagonist and MAO B inhibitory
      properties of several 2-styrylxanthinyl derivatives. A limited structure-activity
      analysis of these compounds and structurally related analogs is provided. The
      results raise the possibility that a single structure may offer the combined
      benefits of two pharmacologic strategies, each with symptomatic and potential
      neuroprotective benefits, for the management of PD.

PMID- 14663014
TI  - Modulation of glutamate release and excitotoxicity by adenosine A2A receptors.
AB  - Because an increased glutamate outflow is thought to play a crucial role in
      triggering excitotoxic neuronal death, drugs able to regulate glutamate release
      could be effective for the management of neurodegenerative diseases. In this
      article, the authors discuss the hypothesis that adenosine A2A receptor
      antagonists (A2A antagonists) may belong to the aforementioned category. In rats
      bilaterally lesioned with the excitotoxin quinolinic acid (QA) in the striatum,
      the A2A antagonist SCH 58261 significantly reduced the motor, EEG, and
      neuropathologic changes induced by the lesion. Such effects of SCH 58261 occurred
      only at low doses and were paralleled by an inhibition of QA-stimulated glutamate
      release. The role played by A2A antagonists in the regulation of glutamate
      outflow was also confirmed by preliminary results obtained in the model of paired
      pulse stimulation in corticostriatal slices. Conversely, based on data obtained
      in cultured striatal neurons, A2A antagonists appear unable to directly inhibit
      NMDA effects. In conclusion, A2A antagonists show clear neuroprotective effects
      in models of brain injury, although their actual therapeutic potential needs to
      be confirmed in a wider range of doses and in models of neurodegenerative
      diseases in which presynaptic and postsynaptic effects play different relative
      roles.

PMID- 14663015
TI  - Adenosine A(2A) receptors in nonlocomotor features of Parkinson's disease:
      introduction.

PMID- 14663016
TI  - Adenosine A2A receptors in neuroadaptation to repeated dopaminergic stimulation:
      implications for the treatment of dyskinesias in Parkinson's disease.
AB  - The A2A receptor has recently attracted considerable interest as a potential
      target for Parkinson's disease (PD) therapy based on the motor-enhancing and
      neuroprotective effects of A2A antagonists in animal models of PD. The unique
      neuronal localization of the adenosine A2A receptor in the basal ganglia and its
      extensive interactions with dopaminergic and glutamatergic systems led the
      authors to investigate a potential role of the A2A receptor in the development of
      behavioral sensitization in response to repeated dopaminergic stimulation.
      Because dopamine-induced behavioral sensitization shares several neurochemical
      and behavioral features with dyskinesia, characterizing this novel aspect of A2A
      receptor function may enhance understanding and management of dyskinesia in PD.
      Recent studies from several laboratories suggest that the A2A receptor may be an
      important mediator of maladaptive changes in response to long-term dopamine
      stimulation. The authors summarize their investigation of the role of A2A
      receptors in two paradigms of behavioral sensitization elicited by daily
      treatment with either L-dopa in hemiparkinsonian mice or amphetamine in naive
      mice. The results demonstrate that the A2A receptor is required for the
      development of behavioral sensitization in response to repeated L-dopa treatment
      in hemiparkinsonian mice and repeated amphetamine administration in normal mice.
      Together with pharmacologic studies, these results raise the possibility that the
      maladaptive dyskinetic responses to long-term L-dopa management of PD may be
      attenuated by A2A receptor blockade. Potential presynaptic, postsynaptic
      (cellular), and trans-synaptic (network) mechanisms are discussed.

PMID- 14663017
TI  - Adenosine A2A receptors and depression.
AB  - Adenosine and its analogues have been shown to induce "behavioral despair" in
      animal models believed to be relevant to depression. Recent data have shown that
      selective adenosine A2A receptor antagonists (e.g., SCH 58261, ZM241385, and
      KW6002) or genetic inactivation of the receptor was effective in reversing signs
      of behavioral despair in the tail suspension and forced swim tests, two screening
      procedures predictive of antidepressant activity. A2A antagonists were active in
      the tail suspension test using either mice previously screened for having high
      immobility scores or mice that were selectively bred for their spontaneous
      "helplessness" in this test. At stimulant doses, caffeine, a nonselective A1/A2A
      receptor antagonist, was effective in the forced swim test. The authors have
      hypothesized that the antidepressant-like effect of selective A2A antagonists is
      linked to an interaction with dopaminergic transmission, possibly in the frontal
      cortex. In support of this idea, administration of the dopamine D2 receptor
      antagonist haloperidol prevented antidepressant-like effects elicited by SCH
      58261 in the forced swim test (putatively involving cortex), whereas it had no
      effect on stimulant motor effects of SCH 58261 (putatively linked to ventral
      striatum). The interaction profile of caffeine with haloperidol differed markedly
      from that of SCH 58261 in the forced swim and motor activity tests. Therefore, a
      clear-cut antidepressant-like effect could not be ascribed to caffeine. In
      conclusion, available data support the proposition that a selective blockade of
      the adenosine A2A receptor may be an interesting target for the development of
      effective antidepressant agents.

PMID- 14663018
TI  - Potential for antipsychotic and psychotomimetic effects of A2A receptor
      modulation.
AB  - The discovery of antagonistic interactions between A2A adenosine receptors and D2
      dopamine receptors in the ventral striatum suggested that A2A receptor activation
      might modulate the antipsychotic effects of dopamine receptor antagonists and
      could provide an opportunity for the development of A2A receptor agonists as
      novel antipsychotic drugs. However, there is limited evidence from preclinical
      and clinical studies that A2A receptor agonists can exert antipsychotic effects.
      Furthermore, it remains unclear whether A2A receptor agonists possess a
      sufficient safety margin or whether their potent hypotensive effects or
      extrapyramidal side effects would limit their therapeutic utility as
      antipsychotic agents. The interaction between A2A receptors and D2 receptors also
      raises the possibility that A2A receptor antagonists, which hold considerable
      promise as antiparkinsonian agents, may have dose-limiting psychotomimetic side
      effects. Preclinical studies using selective A2A receptor antagonists suggest
      that this class of compound has a low propensity to elicit psychotomimetic side
      effects or exacerbate those induced by D2 receptor agonists.

PMID- 14663019
TI  - Sleep regulation in adenosine A2A receptor-deficient mice.

PMID- 14663020
TI  - Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor
      selective antagonist KW6002: research and development toward a novel
      nondopaminergic therapy for Parkinson's disease.
AB  - Research and development of the adenosine A2A receptor selective antagonist
      KW6002 have focused on developing a novel nondopaminergic therapy for Parkinson's
      disease (PD). Salient pharmacologic features of KW6002 were investigated in
      several animal models of PD. In rodent and primate models, KW6002 provides
      symptomatic relief from parkinsonian motor deficits without provoking dyskinesia
      or exacerbating existing dyskinesias. The major target neurons of the A2A
      receptor antagonist were identified as GABAergic striatopallidal medium spiny
      neurons. A possible mechanism of A2A receptor antagonist action in PD has been
      proposed based on the involvement of striatal and pallidal presynaptic A2A
      receptors in the "dual" modulation of GABAergic synaptic transmission.
      Experiments with dopamine D2 receptor knockout mice showed that A2A receptors can
      function and anti-PD activities of A2A antagonists can occur independent of the
      dopaminergic system. Clinical studies of KW6002 in patients with advanced PD with
      L-dopa-related motor complications yielded promising results with regard to motor
      symptom relief without motor side effects. The development of KW6002 represents
      the first time that a concept gleaned from A2A biologic research has been applied
      successfully to "proof of concept" clinical studies. The selective A2A antagonist
      should provide a novel nondopaminergic approach to PD therapy.

PMID- 14663021
TI  - Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of
      Parkinson's disease.
AB  - During a program to investigate the biochemical basis of side effects associated
      with the antimalarial drug mefloquine, the authors made the unexpected discovery
      that the (-)-(R,S)-enantiomer of the drug is a potent adenosine A2A receptor
      antagonist. Although the compound was ineffective in in vivo animal models of
      central adenosine receptor function, it provided a unique nonxanthine adenosine
      A2A receptor antagonist lead structure and encouraged the initiation of a
      medicinal chemistry program to develop novel adenosine A2A antagonists for the
      management of Parkinson's disease (PD). The authors have synthesized and screened
      more than 2,000 chemically diverse and novel adenosine A(2A antagonists. Early
      examples from two distinct chemical series are the thieno[3,2-dy]pyrimidine VER
      6623 and the purine compounds VER-6947 and VER-7835, which have high affinity at
      adenosine A2A receptors (K(i) values 1.4, 1.1, and 1.7 nmol/L, respectively) and
      act as competitive antagonists. In particular, VER-6947 and VER-7835 demonstrate
      potent in vivo activity reversing the locomotor deficit caused by the D2 receptor
      antagonist haloperidol, with minimum effective doses comparable with that of
      KW6002 (0.3 to 1 mg/kg). In conclusion, the authors have discovered potent,
      selective, and in vivo active nonxanthine adenosine A2A antagonists that have
      considerable promise as a new therapy for PD.

PMID- 14663022
TI  - Translating A2A antagonist KW6002 from animal models to parkinsonian patients.
AB  - Improving the translation of novel findings from basic laboratory research to
      better therapies for neurologic disease constitutes a major challenge for the
      neurosciences. This brief review of aspects of the development of an adenosine
      A2A antagonist for use in the management of Parkinson's disease (PD) illustrates
      approaches to some of the relevant issues. Adenosine A2A receptors, highly
      expressed on striatal medium spiny neurons, signal via kinases whose aberrant
      activation has been linked to the appearance of parkinsonian signs after
      dopaminergic denervation and to the motor response complications produced by
      dopaminomimetic therapy. To assess the ability of A2A receptor blockade to
      normalize certain of these kinases and thus benefit motor dysfunction, the
      palliative and prophylactic effects of the selective antagonist KW6002 were first
      evaluated in rodent and primate models. In hemiparkinsonian rats, KW6002 reversed
      the intermittent L-dopa treatment-induced, protein kinase A-mediated
      hyperphosphorylation of striatal alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      proprionic acid receptor GluR1 S845 residues and the concomitant shortening in
      motor response duration. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      lesioned monkeys, coadministration of KW6002 with daily apomorphine injections
      acted prophylactically to prevent dyskinesia onset. These and related preclinical
      observations guided the design of a limited, randomized, controlled, proof-of
      concept study of the A2A antagonist in patients with moderately advanced PD.
      Although KW6002 alone or in combination with a steady-state IV infusion of
      optimal-dose L-dopa had no effect on parkinsonian severity, the drug potentiated
      the antiparkinsonian response to low-dose L-dopa with fewer dyskinesias than
      produced by optimal-dose L-dopa alone. KW6002 also safely prolonged the efficacy
      half-time of L-dopa. The results suggest that drugs capable of selectively
      blocking adenosine A2A receptors could confer therapeutic benefit to L-dopa
      treated parkinsonian patients and warrant further evaluation in phase II studies.
      They also illustrate a strategy for successfully bridging a novel approach to PD
      therapy from an evolving research concept to pivotal clinical trials.

PMID- 14663023
TI  - "At my wits' end": neuroticism and dementia.

PMID- 14663024
TI  - Alzheimer's disease as a window to neural mechanisms of cognition.

PMID- 14663025
TI  - MMT vs MVIC: low-tech scores high?

PMID- 14663027
TI  - The CNS phenotype of X-linked Charcot-Marie-Tooth disease: more than a peripheral
      problem.

PMID- 14663028
TI  - Proneness to psychological distress is associated with risk of Alzheimer's
      disease.
AB  - BACKGROUND: Chronic stress is associated with hippocampal damage and impaired
      memory in animals and humans. OBJECTIVE: To examine this relationship with
      clinical and pathologic data from the Religious Orders Study. METHODS: Older
      Catholic clergy members underwent annual clinical evaluations, which included
      clinical classification of Alzheimer's disease (AD) and detailed cognitive
      function testing from which composite measures of global cognition and specific
      cognitive functions were derived. At the baseline evaluation, participants
      completed a measure of the tendency to experience psychological distress, a
      stable personality trait that served as an indicator of susceptibility to
      negative emotional states across the life span. More than 90% of participants who
      died underwent a uniform postmortem examination of the brain from which summary
      measures of AD pathology were derived. The association of distress proneness with
      incident AD and cognitive decline and with measures of AD pathology was examined
      in analyses adjusted for selected demographic and clinical variables. RESULTS:
      During a mean of 4.9 years of follow-up, 140 persons developed AD. Those high in
      distress proneness (90th percentile) had twice the risk of developing AD than
      those low in distress proneness (10th percentile). Distress proneness was related
      to decline in episodic memory but not in other cognitive domains, with a >10-fold
      increase in episodic memory decline in those high in distress proneness compared
      with those low in the trait. Among those who died, however, distress proneness
      was not related to common measures of AD pathology. CONCLUSION: Proneness to
      experience psychological distress is a risk factor for AD, an effect independent
      of AD pathologic markers such as cortical plaques and tangles.

PMID- 14663030
TI  - Spatial disorientation in Alzheimer's disease: the remembrance of things passed.
AB  - BACKGROUND: Patients with Alzheimer's disease (AD) and many older adults become
      lost even in familiar surroundings. This is commonly attributed to memory
      impairment, but it may reflect impaired spatial cognition. METHODS: The authors
      examined the role of memory, perceptual, and cognitive mechanisms in spatial
      disorientation by comparing the performance of normal young (YN), middle-aged
      (MA), older adult (OA), and AD subjects on neuropsychological and spatial
      orientation tests. RESULTS: The tendency to become lost is shared by almost all
      patients with AD (93%) and some OA subjects (38%). This impairment is not related
      to memory impairment. Instead, it reflects an inability to link recognized scenes
      with locations in the environment. CONCLUSIONS: Spatial disorientation reflects
      the impaired linking of landmarks and routes that should be assessed in
      conjunction with routine memory testing in elderly patients.

PMID- 14663029
TI  - Focal right inferotemporal atrophy in AD with disproportionate visual
      constructive impairment.
AB  - OBJECTIVE: To explore the structural neuroimaging correlates of visual
      constructive impairment in patients with mild to moderate Alzheimer disease (AD).
      BACKGROUND: There is considerable heterogeneity in the non-memory cognitive
      deficits associated with AD. Structural neuroimaging with MRI is an important
      diagnostic tool that is gaining acceptance as a surrogate measure of brain
      pathology in AD treatment trials. Most MRI measurements have focused on medial
      temporal lobe or global cortical atrophy, which may not reflect some important
      clinical features of AD. METHODS: Thirty-two patients with probable AD were
      stratified into two groups based on their relative performance on a visual
      constructive task, the copy of a modified Rey-Osterrieth figure (Rey). The two
      groups did not differ in basic demographic features or in neuropsychological
      performance, other than on the visual constructive task. MRI measurements of
      hippocampal volume, cortical gray matter volume, and focal cortical gray matter
      loss were performed in the patients and a group of 71 age-matched, normal
      controls. RESULTS: Both groups showed significant, bilateral hippocampal as well
      as cortical gray matter volume loss relative to controls. The more spatially
      impaired AD group (SAD) had more right than left cortical gray matter loss,
      whereas the opposite was true in the less spatially impaired group (NSAD). The
      SAD group had significantly less gray matter in the right inferior temporal gyrus
      relative to the NSAD group. Atrophy of this region was correlated with
      performance on the Rey task in all patients with AD. CONCLUSIONS: Right
      inferotemporal atrophy may serve as a neuroimaging marker of visual constructive
      impairment in mild to moderate AD. Heterogeneous cortical atrophy is a common
      feature of AD.

PMID- 14663031
TI  - Idebenone treatment fails to slow cognitive decline in Alzheimer's disease.
AB  - OBJECTIVE: To determine the effect of idebenone on the rate of decline in
      Alzheimer's disease (AD). METHODS: A 1-year, multicenter, double-blind, placebo
      controlled, randomized trial was conducted. Subjects were over age 50 with a
      diagnosis of probable AD and had Mini-Mental State Examination (MMSE) scores
      between 12 and 25. Subjects were treated with idebenone 120, 240, or 360 mg tid,
      each of which was compared with placebo. Primary outcome measures were the
      Alzheimer's Disease Assessment Scale-Cognitive Subcomponent (ADAS-Cog) and a
      Clinical Global Impression of Change (CGIC). Secondary outcome measures included
      measurements of activities of daily living, the Behavioral Pathology in
      Alzheimer's Disease Rating Scale, and the MMSE. RESULTS: Five hundred thirty-six
      subjects were enrolled and randomized to the four groups. Except for a slight
      difference in age, there were no differences in patient characteristics at
      baseline. For the primary outcome measures, there were no significant overall
      differences between the treatment groups in the prespecified four-group design.
      In an exploratory two-group analysis comparing all three treated groups combined
      with placebo, drug-treated patients performed better on the ADAS-Cog in both the
      intent-to-treat (ITT) and completers analyses. There were no differences in the
      CGIC scores for the ITT or completers analyses in either the four-group or the
      two-group analyses. There were no overall differences on any of the secondary
      outcome measures in any of the analyses. CONCLUSION: Idebenone failed to slow
      cognitive decline in AD that was of sufficient magnitude to be clinically
      significant.

PMID- 14663032
TI  - A comparison of muscle strength testing techniques in amyotrophic lateral
      sclerosis.
AB  - OBJECTIVE: To assess the reliability of strength testing techniques among centers
      investigating patients with amyotrophic lateral sclerosis. METHODS: The authors
      compared test reliability in manual muscle testing (MMT) and maximal voluntary
      isometric contraction (MVIC) scores among institutions and test validity by
      comparing change over time between MMT and MVIC. The authors examined 63 subjects
      at 3-month intervals for 12 months. At enrollment and at 6 months, two physical
      therapists each examined the subjects twice. MMT scores were calculated as
      modifications of the Medical Research Council scale. MVIC scores were generated
      as standardized megascores. Intraclass correlation coefficients and coefficients
      of variation compared reproducibility, and Pearson correlation coefficients
      compared change over time. The power of each measure to detect disease
      progression over time was assessed by estimating coefficients of variation for
      the average change. RESULTS: Reproducibility between MVIC and MMT was equivalent.
      Sensitivity to detect progressive weakness and power to detect this change,
      however, favored MMT, an effect largely accounted for by the number of muscles
      sampled. CONCLUSIONS: In multicentered trials, uniformly trained physical
      therapists reproducibly and accurately measure strength by both MMT and MVIC. The
      authors found MMT to be the preferred measure of global strength because of its
      better Pearson correlation coefficients, essentially equivalent reproducibility,
      and more favorable coefficient of variation.

PMID- 14663033
TI  - Subacute inflammatory demyelinating polyneuropathy.
AB  - OBJECTIVE: To report the clinical, electrophysiologic, and histologic
      characteristics of subacute inflammatory demyelinating polyneuropathy (SIDP) and
      to present the diagnostic criteria of this disease. METHODS: For a diagnosis of
      "definite SIDP," there were four mandatory criteria: 1) progressive motor and/or
      sensory dysfunction consistent with neuropathy in more than one limb with time to
      nadir between 4 and 8 weeks, 2) electrophysiologic evidence of demyelination in
      at least two nerves, 3) no other etiology of neuropathy, and 4) no relapse on
      adequate follow-up. Supportive criteria included high spinal fluid protein level
      (>55 mg/dL) and inflammatory cells in the nerve biopsy. A diagnosis of "probable
      SIDP" required progression of demyelinating neuropathy over a 4- to 8-week
      period. RESULTS: Sixteen definite SIDP patients were identified among 29 probable
      SIDP patients. An antecedent infection was found in 38% of cases. The two most
      common neuropathy types were a symmetric motor-sensory neuropathy and a pure
      motor neuropathy. Cranial nerve deficits and respiratory failure were rare.
      Spinal fluid protein was high in 93% of cases. Demyelination was documented by
      the motor nerve conduction in 88% of cases and by the near-nerve needle sensory
      nerve conduction in two cases. Almost all patients were treated with prednisone
      and some with additional immunotherapies. Complete recovery was achieved in 69%
      of cases and partial recovery in others. Definite SIDP had all the
      characteristics of CIDP with three exceptions: a higher rate of antecedent
      infection, no relapse rate, and a high rate of recovery to normal. CONCLUSION:
      Subacute inflammatory demyelinating polyneuropathy is a definite entity bridging
      the gap between Guillain-Barre syndrome and chronic inflammatory demyelinating
      polyneuropathy.

PMID- 14663034
TI  - A CAV3 microdeletion differentially affects skeletal muscle and myocardium.
AB  - BACKGROUND: Caveolin-3 is the muscle-specific protein product of the caveolin
      gene family and an integral membrane component of caveolae. Mutations in the gene
      encoding caveolin-3 (CAV3) underlie four distinct disorders of skeletal muscle:
      the autosomal dominant form of limb-girdle muscular dystrophy type 1C (LGMD-1C),
      rippling muscle disease (RMD), sporadic and familial forms of hyperCKemia, and
      distal myopathy. OBJECTIVE: To characterize a multigenerational Italian family
      affected by an autosomal dominant myopathic disorder and to assess the expression
      of caveolin-3, dystrophin, dystrophin-associated glycoproteins, and neuronal
      nitric oxide synthase in the myocardium of an affected patient. METHODS: Clinical
      analysis involved 15 family members. Skeletal muscle expression of sarcolemmal
      proteins was evaluated by immunohistochemistry and western blot analysis in three
      affected individuals. Caveolar structures were analyzed through electron
      microscopy in muscle biopsies and in one heart biopsy. RESULTS: CAV3 genetic
      analysis showed a heterozygous 3-bp microdeletion (328-330del) in affected
      individuals, resulting in the loss of a phenylalanine (Phe97del) in the
      transmembrane domain. In the skeletal muscle, the mutation was associated with
      severe caveolin-3 deficiency and caveolar disorganization, whereas the expression
      of the other analyzed muscle proteins was unaltered. Remarkably, caveolin-3 was
      expressed in myocardium at a level corresponding to about 60% of that of control
      individuals and was correctly localized at the myocardial cell membranes, with
      preservation of cardiac myofiber caveolar structures. Clinical analysis revealed
      the concomitant presence in this family of the following phenotypes: RMD, LGMD,
      and hyperCKemia. CONCLUSIONS: Intrafamilial phenotypic heterogeneity is
      associated with caveolin-3 Phe97 microdeletion. The molecular network interacting
      with caveolin-3 in skeletal muscle and heart may differ.

PMID- 14663035
TI  - Autosomal dominant hyaline body myopathy: clinical variability and pathologic
      findings.
AB  - OBJECTIVE: To report clinical, morphologic, and immunohistochemical studies on
      autosomal dominant, clinically nonprogressive, and not previously described
      progressive forms of hyaline body (HB) myopathy (HBM) in a Saudi Arabian kindred.
      RESULTS: Muscle biopsies from four patients showed HB in type 1 fibers; they were
      positive for ATPase at pH 4.3/4.6 and for heavy chain slow myosin (HCSM); some HB
      were HCSM negative. HB were nonreactive for alphaB-crystallin, ubiquitin,
      tropomyosin, actins, desmin, and components of sarcolemma. Ultrastructurally, HB
      were granular and filamentous or amorphous, often with fragments of sarcomeres,
      and surrounded by a zone of sarcomeric disorganization. All biopsies showed
      "myopathic" changes, angulated neurogenic fibers, and fiber type grouping. There
      was no correlation between HB and course of disease; the progressive cases
      displayed more severe myopathic features. CONCLUSIONS: Formation of hyaline
      bodies in hyaline body myopathy is associated with either myolysis or defective
      incorporation of heavy chain slow myosin into the cytoskeleton. Hyaline bodies
      very likely contain additional unidentified proteins. Neurogenic factors are also
      involved in the hyaline body myopathy pathogenesis.

PMID- 14663036
TI  - Major depression in multiple sclerosis: a population-based perspective.
AB  - OBJECTIVE: To determine the prevalence of major depression in multiple sclerosis
      (MS) in a population-based sample controlling for nonspecific illness effects.
      METHODS: This study used data from a large-scale national survey conducted in
      Canada: the Canadian Community Health Survey (CCHS). The analysis included
      115,071 CCHS subjects who were 18 years or older at the time of data collection.
      The CCHS interview obtained self-reported diagnoses of MS and employed a brief
      predictive interview for major depression: the Composite International Diagnostic
      Interview Short Form for Major Depression. The 12-month period prevalence of
      major depression was estimated in subjects with and without MS and with and
      without other long-term medical conditions. RESULTS: The prevalence of major
      depression was elevated in persons with MS relative to those without MS and those
      reporting other conditions. The association persisted after adjustment for age
      and sex (adjusted odds ratio = 2.3, 95% CI 1.6 to 3.3). Major depression
      prevalence in MS for those in the 18- to 45-year age range was high at 25.7% (95%
      CI 15.6 to 35.7). CONCLUSIONS: The prevalence of major depression in the
      population with MS is elevated. This elevation is not an artifact of selection
      bias and exceeds that associated with having one or more other long-term
      conditions.

PMID- 14663037
TI  - Effect of relapses on development of residual deficit in multiple sclerosis.
AB  - OBJECTIVE: To determine the percentage of patients with residual deficits
      following multiple sclerosis (MS) exacerbations and the magnitude of those
      deficits using a database of pooled placebo patients from clinical trials.
      METHODS: A database of patients assigned to the placebo group in several
      randomized clinical trials was queried to determine those patients with Expanded
      Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale assessments
      prior to, at the time of, and after an acute exacerbation of MS. The extent of
      deficit present at these time points was compared to determine the acute effect
      of exacerbations and the degree of persistent disability. RESULTS: Forty-two
      percent of patients had residual deficit of at least 0.5 and 28% had residual of
      >or=1.0 EDSS units, at an average of 64 days after an exacerbation. The results
      were reproduced across subsequent exacerbations and were sustained over time. The
      subgroup of patients with measurable change in EDSS during the exacerbation had
      more extensive residual impairment on the follow-up visits. Similar results were
      seen when the Scripps score was examined. CONCLUSION: MS exacerbations produce a
      measurable and sustained effect on disability.

PMID- 14663038
TI  - Stimulus recognition and its relationship to the cerebral event-related
      potential.
AB  - BACKGROUND: The relationship between the event-related cerebral potential (ERP)
      and perceptual awareness by the subject is poorly understood. The authors
      manipulated the process of stimulus recognition to examine the effect of changes
      in a subject's awareness on different components of the ERP and on behavioral
      (motor) responses. METHODS: Ten subjects listened to a series of 400 tone pips,
      one of which (frequent tone) was slightly louder than the other (rare tone; 14%
      of trials). Stimuli were presented in blocks of 10 tones and, following each
      block, subjects were asked how many rare tones they had detected and if they were
      aware of any errors that they had made during that block. Cerebral and motor
      responses were recorded by surface electrodes. RESULTS: When subjects were aware
      of having responded erroneously to either the rare or frequent tone, their
      response times were shorter than for correct responses to that tone. When
      subjects were unaware of such errors, however, the response times were delayed
      compared to correct responses and to error responses of which the subject was
      aware. When the subject made an error by responding to the rare tone as if it
      were frequent and was aware of the error, the N2 and P3 latencies were delayed.
      By contrast, when subjects were unaware of such errors, no N2 or P3 components
      were present. Similar findings were noted when subjects responded to a frequent
      tone as if it were rare. CONCLUSIONS: These results suggest that the N2 and P3
      components of the ERP reflect the awareness of the subject that an unexpected
      event has occurred, regardless of whether it is an unexpected stimulus or an
      unexpectedly erroneous response to that stimulus. The recording of ERP may
      provide a means of measuring perceptual awareness in other contexts.

PMID- 14663039
TI  - Involvement of the human subthalamic nucleus in movement preparation.
AB  - BACKGROUND: Although it has long been recognized that the basal ganglia play a
      major role in motor control, their precise functions remain unclear. As patients
      with Parkinson's disease (PD) have difficulties initiating movement, the basal
      ganglia may be involved in movement preparation. The subthalamic nucleus (STN) is
      particularly suited to play a role in movement preparation because it receives
      direct input from the supplementary motor area through the corticosubthalamic
      pathway. METHODS: Taking advantage of the electrodes surgically implanted in the
      STN for deep brain stimulation (DBS) treatment in 13 PD patients, we recorded
      from the DBS electrodes and the scalp simultaneously while the patients were
      performing self-paced wrist extension movements. RESULTS: Scalp recordings showed
      a slow, negative movement-related potential (MRP) in all patients studied (onset
      1,690 +/- 336 milliseconds before electromyography onset). STN recordings showed
      premovement MRP in 11 of 13 patients. The STN activity occurred with both
      ipsilateral and contralateral hand movement. The onset time for STN MRP
      (contralateral 2,095 +/- 1,005 milliseconds, ipsilateral 2,020 +/- 920
      milliseconds) was not significantly different from that for cortical MRP.
      CONCLUSION: The STN or nearby structures are active before self-paced movement in
      humans.

PMID- 14663040
TI  - Effects of botulinum toxin on motor system excitability in patients with writer's
      cramp.
AB  - OBJECTIVE: To investigate botulinum toxin (BTX) effects on central and peripheral
      motor excitability in writer's cramp. METHODS: Using transcranial magnetic
      stimulation over the motor cortex and brainstem and peripheral electrical
      stimulation, the authors investigated measures of motor cortical and peripheral
      motor excitability on the affected and unaffected side before and 2 to 4 weeks
      after BTX A injection into the affected muscles in six patients with writer's
      cramp. The following motor excitability measures were studied: resting and active
      motor threshold, cortical silent period, intracortical inhibition and
      facilitation using the double-pulse technique, recruitment curves, motor evoked
      potentials following magnetic brainstem stimulation, and maximum M-response
      amplitude following supramaximal peripheral nerve stimulation. RESULTS: BTX
      injection improved function and reduced the M response. No other measures of
      motor system excitability showed significant changes following BTX injection, and
      there was no difference in these measures between sides. CONCLUSIONS: BTX A
      effects on motor system excitability seem to be based mainly on its peripheral
      mechanisms of action. There was no difference in the motor system excitability
      between the clinically affected and unaffected sides in this group of patients.

PMID- 14663041
TI  - Dosage effects of riluzole in Huntington's disease: a multicenter placebo
      controlled study.
AB  - BACKGROUND: Riluzole retards striatal glutamate release and pathologic
      consequences in neurotoxic animal models of Huntington's disease (HD). OBJECTIVE:
      To determine the dosage-related impact of riluzole on chorea in HD. METHODS: An 8
      week double-blind dose-ranging multicenter study of riluzole was conducted in 63
      subjects (32 women, 31 men) with HD who were randomized to receive placebo,
      riluzole 100 mg/day, or riluzole 200 mg/day. The prespecified outcome measure was
      change in the total maximal chorea score of the Unified Huntington's Disease
      Rating Scale (UHDRS). RESULTS: Fifty-six (89%) subjects completed the study. A
      reduction (p < 0.01) in chorea at 8 weeks was found using a linear trend test
      with dose. Comparing the groups individually, the reduction in chorea for the
      riluzole 200-mg/day group (-2.2 +/- 3.3) was different (p = 0.01) from placebo
      (+0.7 +/- 3.4), but the riluzole 100-mg/day group (-0.2 +/- 2.9) was not.
      Riluzole did not improve other motor, cognitive, behavioral, or functional
      components of the UHDRS. Alanine aminotransferase was elevated in a dosage
      dependent fashion (p = 0.01). CONCLUSIONS: Over 8 weeks of treatment, riluzole
      200 mg/day ameliorated chorea intensity in HD without improving functional
      capacity or other clinical features of illness. Riluzole 200 mg/day was attended
      by reversible liver transaminase abnormalities that would require monitoring in
      long-term studies.

PMID- 14663042
TI  - A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the
      GenePD study.
AB  - OBJECTIVE: To identify a haplotype influencing onset age for Parkinson's disease
      (PD) in the PARK3 region on chromosome 2p13. METHODS: Single nucleotide
      polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate
      genes were used to fine map the PARK3 region in 527 patients with familial PD,
      from 264 families. RESULTS: TT homozygotes for rs1876487 (G/T) had a 7.4-year
      younger mean age at onset (p = 0.005) compared to patients with GT and GG
      genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8
      dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and
      rs1150500 (p = 0.04), were associated with younger onset age among persons who
      did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine
      synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244
      revealed an association with onset age (p = 0.023) and a haplotype of A-T-G
      alleles was associated with younger onset for PD (p = 0.005). CONCLUSIONS: A
      haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset
      age of PD. This may suggest a role for the SPR gene in modifying the age at onset
      of PD.

PMID- 14663043
TI  - Unexpectedly low prevalence and unusual characteristics of RLS in Mersin, Turkey.
AB  - OBJECTIVE: To determine the prevalence, risk factors, and clinical presentation
      of restless legs syndrome (RLS) in a Turkish population. METHODS: A face-to-face,
      population-based epidemiologic survey was conducted. Multistep, stratified,
      cluster, and systematic samplings were used. A total of 3,234 adults were
      interviewed. RESULTS: Of the 3,234 participants, 103 (3.19%) experienced RLS.
      This prevalence rate is lower than those of other epidemiologic studies conducted
      among European and North American populations. RLS was found to be more common
      among women, cigarette smokers, and individuals residing in high altitudes. The
      self-reported mental and general health status of patients was worse than in the
      control subjects. The prevalence of RLS did not differ by age or body mass index.
      CONCLUSION: The discrepancy in RLS prevalence studies (including the authors')
      suggests that prevalence varies among different races, thus supporting a genetic
      predisposition.

PMID- 14663044
TI  - MRI in chronic spinal cord injury patients with and without central pain.
AB  - BACKGROUND: Central pain following spinal cord injury (SCI) is common and thought
      to be related to lesion of the spinothalamic pathways. OBJECTIVE: To examine
      additional mechanisms of SCI pain. METHODS: Twenty-three SCI patients with
      traumatic lesions above T10 (14 with central neuropathic pain and 9 without pain)
      underwent MRI examination. The authors quantitatively assessed extent of cord
      lesion on axial T2-weighted images as percentage of 1) gray matter, 2)
      dorsolateral, 3) anterolateral, and 4) dorsolateral columns based on standardized
      drawings made by a neuroradiologist blinded to patient history. RESULTS: At the
      level of maximal cord injury, 21 patients had lesions involving the entire cord
      on axial images except for a small border of lower signal intensity, whereas 2
      patients had central lesions. Rostral to the main injury, the first image with an
      incomplete lesion showed significantly more involvement of gray matter in pain
      than in pain-free patients. CONCLUSION: Consistent with animal models of SCI,
      spinothalamic tract lesion together with neuronal hyperexcitability due to lesion
      of inhibitory interneurons at the rostral end of injury are hypothesized to lead
      to central pain.

PMID- 14663045
TI  - Genetic influences on myoclonic and absence seizures.
AB  - OBJECTIVE: To examine the relationship between genotype and phenotype in
      idiopathic generalized epilepsies (IGEs) using a novel approach that focuses on
      seizure type rather than syndrome. METHODS: The authors evaluated whether the
      genetic effects on myoclonic seizures differ from the genetic effects on absence
      seizures. For this purpose, they studied 34 families containing 2 or more members
      with IGEs and assessed whether the number of families concordant for seizure type
      exceeded that expected by chance. The authors performed a similar analysis to
      examine the genetic contributions to juvenile myoclonic epilepsy (JME), juvenile
      absence epilepsy (JAE), and childhood absence epilepsy (CAE). RESULTS: The
      observed number of families concordant for seizure type (myoclonic, absence, or
      both) was greater than expected (20 vs 7.51; p < 0.0001). The observed number of
      families concordant for syndrome was greater than expected when JME was compared
      with absence epilepsies (JAE+CAE) (17 vs 11.9; p < 0.012) but not when JAE was
      compared with CAE (8 vs 6.82; p = 0.516). CONCLUSIONS: These results provide
      evidence for distinct genetic effects on absence and myoclonic seizures,
      suggesting that examining the two seizure types separately would be useful in
      linkage studies of idiopathic generalized epilepsies. The approach presented here
      can also be used to discover other clinical features that could direct division
      of epilepsies into groups likely to share susceptibility genes.

PMID- 14663046
TI  - Memory assessment during the intracarotid amobarbital procedure: influence of
      injection order.
AB  - OBJECTIVE: To analyze, in patients with unilateral regional epilepsy, the
      influence of intracarotid amobarbital injection order on the level of recognition
      memory, with both injections performed within approximately half an hour, when
      the order was varied by a first injection into either the epileptogenic or the
      nonepileptogenic hemisphere. METHODS: Of a series of 74 consecutive intracarotid
      amobarbital procedures (IAP), 61 valid bilateral tests were extracted for
      analysis. The protocol was changed from a congruent sequence (epileptogenic
      hemisphere injected first; n = 32) to an incongruent sequence (nonepileptogenic
      hemisphere injected first; n = 29). Memory was quantified by the percentage of
      presented items recognized before the recovery of full motor power (corrected for
      guessing). RESULTS: The congruent group showed a poorer recognition percentage
      after injection into the nonepileptogenic hemisphere than after injection into
      the epileptogenic hemisphere. The incongruent group had a similar recognition
      percentage after both injections. This was especially apparent in patients with a
      right epileptogenic hemisphere. CONCLUSIONS: The commonly used congruent
      injection order leads to a poorer recognition by the epileptogenic hemisphere
      than the nonepileptogenic hemisphere. This relation cannot be found with an
      incongruent sequence. The results raise doubts about the internal validity of the
      IAP in describing isolated hemispheric memory functions.

PMID- 14663047
TI  - Prevalence and clinical features of HTLV neurologic disease in the HTLV Outcomes
      Study.
AB  - BACKGROUND: Almost 20 years after its discovery, the prevalence and clinical
      course of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM,
      also known as tropical spastic paraparesis [TSP]) remain poorly defined. Whereas
      the causative association of HTLV-I and HAM/TSP is generally recognized,
      controversy still surrounds the relationship between HTLV-II and HAM/TSP.
      METHODS: The HTLV Outcomes Study (HOST-formerly Retrovirus Epidemiology Donor
      Study [REDS]) is a prospective cohort study including 160 patients with HTLV-I,
      405 patients with HTLV-II, and 799 uninfected controls who have been followed
      every 2 years since 1990-1992. Clinical outcomes are measured by health
      interviews and examinations, and blood samples are obtained. RESULTS: Six cases
      of HTLV-I-associated myelopathy (3.7%, 95% CI 1.4 to 8.0) and four cases of HTLV
      II myelopathy (1.0%, 95% CI 0.3 to 2.5) have been diagnosed since the formation
      of the cohort. There have been no cases of HAM/TSP diagnosed among HTLV-negative
      subjects (0.0%, 95% CI 0.0 to 0.5). Clinical features of the cases include lower
      extremity hyperreflexia, variably associated with weakness, spasticity, and
      bladder dysfunction. CONCLUSIONS: Systematic screening of HTLV-infected blood
      donors reveals a high prevalence of HAM/TSP. The clinical course of HAM/TSP
      appears highly variable. HTLV-II-associated myelopathy generally presents with
      milder and more slowly progressive signs and symptoms.

PMID- 14663048
TI  - Hyperhomocysteinemia as an independent risk factor for silent brain infarction.
AB  - OBJECTIVE: To evaluate whether hyperhomocysteinemia is an independent risk factor
      for silent brain infarction (SBI), and to determine the relationship between
      homocysteine and folate in each type of methylenetetrahydrofolate reductase
      (MTHFR) polymorphism, in order to identify a way of reducing the risk for SBI.
      METHODS: The authors enrolled 161 patients with SBI and 126 healthy people,
      checked their fasting homocysteine and folate levels, and analyzed for the MTHFR
      C677T polymorphism. RESULTS: The mean plasma homocysteine level in patients with
      SBI (12.17 +/- 5.35 micro mol/L) was significantly higher than in normal healthy
      people (9.37 +/- 4.11 micro mol/L; p < 0.05). By subgroup analysis, based on the
      classification of plasma homocysteine levels as high (>or=11.77 micro mol/L),
      moderate (8.71 to 11.76 micro mol/L), and low (<or=8.70 micro mol/L), the
      adjusted OR (AOR) of the high group for SBI was significantly greater than that
      of the low group (AOR, 4.78; 95% CI, 2.45 to 9.33). The homocysteine level showed
      a significant inverse correlation with folate level only in patients with SBI
      with the MTHFR 677TT genotype (p < 0.05). CONCLUSIONS: This study demonstrates
      that hyperhomocysteinemia is an independent risk factor for SBI, and provides the
      possibility of reducing the risk for SBI in the MTHFR 677TT genotype by folate
      supplementation.

PMID- 14663049
TI  - MRI in ALS: corticospinal tract hyperintensity.

PMID- 14663050
TI  - Long-term follow-up of thalamic deep brain stimulation for essential and
      parkinsonian tremor.
AB  - Thirteen consecutive patients with thalamic deep brain stimulation (DBS) were
      examined serially for 3 to 5 years. Initially, all demonstrated at least 50%
      improvement in contralateral tremor. At last follow-up, three of eight patients
      with Parkinson disease no longer used DBS because tremor had markedly improved,
      and for two, motor fluctuations and levodopa-induced dyskinesias became the major
      disability, with tremor less troublesome. Two of five patients with essential
      tremor had contralateral tremor improvement after ongoing stimulation for 2
      years; two developed marked tolerance to DBS.

PMID- 14663052
TI  - Diagnostic value of sural nerve matrix metalloproteinase-9 in diabetic patients
      with CIDP.
AB  - Patients with diabetes mellitus (DM) may develop chronic inflammatory
      demyelinating polyneuropathy (CIDP), which may be difficult to distinguish from
      diabetic neuropathy (DNP). Here the authors show that immunoreactivity for matrix
      metalloproteinase-9 on sural nerve biopsies may help to identify CIDP-DM. In a
      pilot study on 10 CIDP-DM patients with IV immunoglobulins and tight glycemic
      control, the CIDP-DM patients had a better outcome than DNP patients treated with
      tight glycemic control only.

PMID- 14663051
TI  - Robot-aided sensorimotor arm training improves outcome in patients with chronic
      stroke.
AB  - Thirty patients with chronic stroke received 6 weeks of sensorimotor robotic
      training in a pilot study that targeted motor function of the affected shoulder
      and elbow. The impairment and disability scores were stable during a 2-month
      observation/measurement period, improved significantly by program completion, and
      remained robust in the 3-month follow-up. Task-specific motor training attenuated
      a chronic neurologic deficit well beyond the expected period for improvement
      after stroke.

PMID- 14663053
TI  - Skin biopsy in Lafora disease: genotype-phenotype correlations and diagnostic
      pitfalls.
AB  - Lafora disease is characterized by pathognomonic inclusions, Lafora bodies (LB),
      in neurons and other cell types. In skin, LB have been reported in either eccrine
      sweat glands or in apocrine sweat glands. The disease is caused by mutations in
      either the EPM2A gene or in a second yet-unknown gene. Here the authors determine
      whether a genotype-phenotype correlation exists between the genetic form of the
      disease and the skin cell type affected by LB formation. Also is described an
      important source of false positivity in the use of axillary biopsies for disease
      diagnosis.

PMID- 14663054
TI  - Mutation in the CHAC gene in a family of autosomal dominant chorea
      acanthocytosis.
AB  - Although mutations in the CHAC gene have been identified in autosomal recessive
      chorea-acanthocytosis (AR-ChAc), the molecular basis of autosomal dominant ChAc
      (AD-ChAc) remains to be determined. The authors investigated abnormalities in the
      CHAC gene in an AD-ChAc family with mRNA and sequencing analyses of mRNA and
      genomic DNA. A novel single heterozygous mutation in the last nucleotide of exon
      57 of the CHAC gene, which could cause skipping of the exon, was detected in
      affected siblings.

PMID- 14663055
TI  - Comparison of PCR-amplified JC virus control region sequences from multiple brain
      regions in PML.
AB  - The authors report a 14-year-old boy with Wiskott-Aldrich syndrome complicated by
      progressive multifocal leukoencephalopathy after allogeneic bone marrow
      transplantation. Several therapeutic approaches were attempted, but there was no
      response. The patient died 2 months after the onset of neurologic symptoms. We
      detected three distinct, rearranged regions of JC virus in the cerebellum,
      occipital lobe, and brainstem. These findings suggest that the brain lesions had
      three independent origins.

PMID- 14663056
TI  - The "split hand" phenomenon: evidence of a spinal origin.
AB  - The clinical phenomenon of a split hand, dominant muscle atrophy in the thenar as
      compared to the hypothenar complex, has been used to support the theory of
      primary cortical degeneration in amyotrophic lateral sclerosis. However, the same
      phenomenon, both clinically and electrophysiologically, was observed in three
      diseases with a second but not first motor neuron affection: autosomal dominant
      spinal muscular atrophy, spinocerebellar ataxia type 3, and juvenile muscular
      atrophy. Neurogenic loss in a split hand distribution points to a spinal instead
      of cortical origin.

PMID- 14663057
TI  - Oculopalatal tremor after pontine hemorrhage.

PMID- 14663058
TI  - Early diagnosis of spinal cord infarct using magnetic resonance diffusion
      imaging.

PMID- 14663059
TI  - Paraneoplastic limbic encephalitis (PLE) and chorea associated with CRMP-5
      neuronal antibody.

PMID- 14663060
TI  - A corticosteroid-responsive aneurysmal lenticulostriate vasculopathy.

PMID- 14663061
TI  - Serum substance P concentrations and silent aspiration in elderly patients with
      stroke.

PMID- 14663062
TI  - Proteomic applications for differential diagnosis of histologically identical
      tumors.

PMID- 14663063
TI  - Report of the Therapeutics and Technology Assessment Subcommittee of the American
      Academy of Neurology.

PMID- 14663064
TI  - Major malformations in offspring of women with epilepsy.

PMID- 14663065
TI  - Antecedent to hippocampal sclerosis and temporal lobe epilepsy?

PMID- 14663066
TI  - Concerns regarding resistance to self-proteins.

PMID- 14663068
TI  - Facing extremes: archaeal surface-layer (glyco)proteins.
AB  - Archaea are best known in their capacities as extremophiles, i.e. micro-organisms
      able to thrive in some of the most drastic environments on Earth. The protein
      based surface layer that envelopes many archaeal strains must thus correctly
      assemble and maintain its structural integrity in the face of the physical
      challenges associated with, for instance, life in high salinity, at elevated
      temperatures or in acidic surroundings. Study of archaeal surface-layer
      (glyco)proteins has thus offered insight into the strategies employed by these
      proteins to survive direct contact with extreme environments, yet has also served
      to elucidate other aspects of archaeal protein biosynthesis, including
      glycosylation, lipid modification and protein export. In this mini-review, recent
      advances in the study of archaeal surface-layer (glyco)proteins are discussed.

PMID- 14663069
TI  - Use of a two-hybrid assay to study the assembly of a complex multicomponent
      protein machinery: bacterial septosome differentiation.
AB  - The ability of each of the nine Escherichia coli division proteins (FtsZ, FtsA,
      ZipA, FtsK, FtsQ, FtsL, FtsW, FtsI, FtsN) to interact with itself and with each
      of the remaining eight proteins was studied in 43 possible combinations of
      protein pairs by the two-hybrid system previously developed by the authors'
      group. Once the presumed interactions between the division proteins were
      determined, a model showing their temporal sequence of assembly was developed.
      This model agrees with that developed by other authors, based on the co
      localization sequence in the septum of the division proteins fused with GFP. In
      addition, this paper shows that the authors' assay, which has already proved to
      be very versatile in the study of prokaryotic and eukaryotic protein interaction,
      is also a powerful instrument for an in vivo study of the interaction and
      assembly of proteins, as in the case of septum division formation.

PMID- 14663070
TI  - Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin
      component (HA1) of the progenitor toxin from Clostridium botulinum.
AB  - Botulism food poisoning is caused primarily by ingestion of the Clostridium
      botulinum neurotoxin (BoNT). The 1300 amino acid BoNT forms a progenitor toxin
      (PTX) that, when associated with a number of other proteins, increases its oral
      toxicity by protecting it from the low pH of the stomach and from intestinal
      proteases. One of these associated proteins, HA1, has also been suggested to be
      involved with internalization of the toxin into the bloodstream by binding to
      oligosaccharides lining the intestine. Here is reported the crystal structure of
      HA1 from type C Clostridium botulinum at a resolution of 1.7 Angstrom. The
      protein consists of two beta-trefoil domains and bears structural similarities to
      the lectin B-chain from the deadly plant toxin ricin. Based on structural
      comparison to the ricin B-chain lactose-binding sites, residues of type A HA1
      were selected and mutated. The D263A and N285A mutants lost the ability to bind
      carbohydrates containing galactose moieties, implicating these residues in
      carbohydrate binding.

PMID- 14663071
TI  - High-affinity myo-inositol transport in Candida albicans: substrate specificity
      and pharmacology.
AB  - Inositol is considered a growth factor in yeast cells and it plays an important
      role in Candida as an essential precursor for phospholipomannan, a
      glycophosphatidylinositol (GPI)-anchored glycolipid on the cell surface of
      Candida which is involved in the pathogenicity of this opportunistic fungus and
      which binds to and stimulates human macrophages. In addition, inositol plays an
      essential role in the phosphatidylinositol signal transduction pathway, which
      controls many cell cycle events. Here, high-affinity myo-inositol uptake in
      Candida albicans has been characterized, with an apparent K(m) value of 240 +/-
      15 microM, which appears to be active and energy-dependent as revealed by
      inhibition with azide and protonophores (FCCP, dinitrophenol). Candida myo
      inositol transport was sodium-independent but proton-coupled with an apparent
      K(m) value of 11.0 +/- 1.1 nM for H(+), equal pH 7.96 +/- 0.05, suggesting that
      the C. albicans myo-inositol-H(+) transporter is fully activated at physiological
      pH. C. albicans inositol transport was not affected by cytochalasin B, phloretin
      or phlorizin, an inhibitor of mammalian sodium-dependent inositol transport.
      Furthermore, myo-inositol transport showed high substrate specificity for
      inositol and was not significantly affected by hexose or pentose sugars as
      competitors, despite their structural similarity. Transport kinetics in the
      presence of eight different inositol isomers as competitors revealed that proton
      bonds between the C-2, C-3 and C-4 hydroxyl groups of myo-inositol and the
      transporter protein play a critical role for substrate recognition and binding.
      It is concluded that C. albicans myo-inositol-H(+) transport differs kinetically
      and pharmacologically from the human sodium-dependent myo-inositol transport
      system and constitutes an attractive target for delivery of cytotoxic inositol
      analogues in this pathogenic fungus.

PMID- 14663072
TI  - Differential regulation of the Proteus mirabilis urease gene cluster by UreR and
      H-NS.
AB  - Proteus mirabilis, a cause of catheter-associated urinary tract infection, relies
      on several virulence factors to colonize the urinary tract. Among these, urease
      contributes to the development of urinary stones resulting from the increase in
      local pH due to urease-mediated hydrolysis of urea to NH(3) and CO(2). UreR, an
      AraC-like transcriptional activator, activates transcription of the genes
      encoding the urease subunits and accessory proteins (ureDABCEFG) in the presence
      of urea. UreR also initiates transcription of its own gene in a urea-inducible
      manner by binding to the intergenic region between ureR and ureD. The intergenic
      region contains poly(A) tracts that appear to be the target of H-NS. It has been
      shown that Escherichia coli and P. mirabilis H-NS acts to repress transcription
      of ureR in an E. coli model system. It was hypothesized that H-NS represses
      urease gene expression in the absence of UreR and urea by binding to the
      intergenic region. To demonstrate this the P. mirabilis hns gene was cloned and
      the 15.6 kDa H-NS was overexpressed and purified as a myc-His tail fusion. Using
      a gel shift assay, purified H-NS-myc-His bound preferentially to a 609 bp DNA
      fragment containing the entire ureR-ureD intergenic region. H-NS and UreR were
      able to displace each other from the ureR-ureD intergenic region. Circular
      permutation analysis revealed that the intergenic region is bent. Moreover, H-NS
      recognizes this curvature, binds the DNA fragment and induces further bending of
      the DNA as shown by a circular ligation assay. The effects of H-NS, urea and
      temperature (25 vs 37 degrees C) on urease expression were shown in E. coli
      containing an hns knockout and P. mirabilis where expression was increased at 37
      degrees C. Increased transcription from p(ureR) was seen in the E. coli hns
      knockout when temperature was increased from 25 to 37 degrees C. These findings
      suggest H-NS and UreR differentially regulate urease in a negative and positive
      manner, respectively.

PMID- 14663073
TI  - The Bradyrhizobium japonicum napEDABC genes encoding the periplasmic nitrate
      reductase are essential for nitrate respiration.
AB  - The napEDABC gene cluster that encodes the periplasmic nitrate reductase from
      Bradyrhizobium japonicum USDA110 has been isolated and characterized. napA
      encodes the catalytic subunit, and the napB and napC gene products are predicted
      to be a soluble dihaem c and a membrane-anchored tetrahaem c-type cytochrome,
      respectively. napE encodes a transmembrane protein of unknown function, and the
      napD gene product is a soluble protein which is assumed to play a role in the
      maturation of NapA. Western blots of the periplasmic fraction from wild-type
      cells grown anaerobically with nitrate revealed the presence of a protein band
      with a molecular size of about 90 kDa corresponding to NapA. A B. japonicum
      mutant carrying an insertion in the napA gene was unable to grow under nitrate
      respiring conditions, lacked nitrate reductase activity, and did not show the 90
      kDa protein band. Complementation of the mutant with a plasmid bearing the
      napEDABC genes restored both nitrate-dependent anaerobic growth of the cells and
      nitrate reductase activity. A membrane-bound and a periplasmic c-type cytochrome,
      with molecular masses of 25 kDa and 15 kDa, respectively, were not detected in
      the napA mutant strain incubated anaerobically with nitrate, which identifies
      those proteins as the NapC and the NapB components of the B. japonicum
      periplasmic nitrate reductase enzyme. These results suggest that the periplasmic
      nitrate reductase is the enzyme responsible for anaerobic growth of B. japonicum
      under nitrate-respiring conditions. The promoter region of the napEDABC genes has
      been characterized by primer extension. A major transcript initiates 66.5 bp
      downstream of the centre of a putative FNR-like binding site.

PMID- 14663074
TI  - Fine-tuned regulation by oxygen and nitric oxide of the activity of a semi
      synthetic FNR-dependent promoter and expression of denitrification enzymes in
      Paracoccus denitrificans.
AB  - In Paracoccus denitrificans at least three fumarate and nitrate reductase
      regulator (FNR)-like proteins [FnrP, nitrite and nitric oxide reductases
      regulator (NNR) and NarR] control the expression of several genes necessary for
      denitrifying growth. To gain more insight into this regulation, beta
      galactosidase activity from a plasmid carrying the lacZ gene fused to the
      Escherichia coli melR promoter with the consensus FNR-binding (FF) site was
      examined. Strains defective in the fnrP gene produced only very low levels of
      beta-galactosidase, indicating that FnrP is the principal activator of the FF
      promoter. Anoxic beta-galactosidase levels were much higher relative to those
      under oxic growth and were strongly dependent on the nitrogen electron acceptor
      used, maximal activity being promoted by N(2)O. Additions of nitrate or
      nitroprusside lowered beta-galactosidase expression resulting from an oxic to
      micro-oxic switch. These results suggest that the activity of FnrP is influenced
      not only by oxygen, but also by other factors, most notably by NO concentration.
      Observations of nitric oxide reductase (NOR) activity in a nitrite-reductase
      deficient strain and in cells treated with haemoglobin provided evidence for dual
      regulation of the synthesis of this enzyme, partly independent of NO. Both
      regulatory modes were operative in the FnrP-deficient strain, but not in the NNR
      deficient strain, suggesting involvement of the NNR protein. This conclusion was
      further substantiated by comparing the respective NOR promoter activities.

PMID- 14663075
TI  - Two MerR homologues that affect copper induction of the Bacillus subtilis copZA
      operon.
AB  - Copper ions induce expression of the Bacillus subtilis copZA operon encoding a
      metallochaperone, CopZ, and a CPx-type ATPase efflux protein, CopA. The copZA
      promoter region contains an inverted repeat sequence similar to that recognized
      by the mercury-sensing MerR protein. To investigate the possible involvement of
      MerR homologues in copZA regulation, null mutations were engineered affecting
      each of four putative MerR-type regulators: yyaN, yraB, yfmP and yhdQ. Two of
      these genes affected copper regulation. Mutation of yhdQ (hereafter renamed cueR)
      dramatically reduced copper induction of copZA, and purified CueR bound with high
      affinity to the copZA promoter region. These results suggest that CueR is a
      direct regulator of copZA transcription that mediates copper induction.
      Surprisingly, a yfmP mutation also reduced copper induction of copZA. Sequence
      analysis suggested that yfmP was cotranscribed with yfmO, encoding a putative
      multidrug efflux protein. The yfmPO operon is autoregulated: a yfmP mutation
      derepressed the yfmP promoter and purified YfmP bound the yfmP promoter region,
      but not the copZA promoter region. Since the yfmP mutant strain was predicted to
      express elevated levels of the YfmO efflux pump, it was hypothesized that copper
      efflux might be responsible for the reduced copZA induction. Consistent with this
      model, in a yfmP yfmO double mutant copper induction of copZA was normal. The
      results demonstrate the direct regulation of the B. subtilis copper efflux system
      by CueR, and indirect regulation by a putative multidrug efflux system.

PMID- 14663076
TI  - Identification of functionally important regions of a haemoglobin receptor from
      Neisseria meningitidis.
AB  - The HmbR outer-membrane receptor enables Neisseria meningitidis to use
      haemoglobin (Hb) as a source of iron. This protein functions by binding Hb,
      removing haem from it, and releasing the haem into the periplasm. Functionally
      important HmbR receptor domains were discerned using a series of HmbR deletions
      and site-directed mutations. Mutations exhibiting similar defective phenotypes in
      N. meningitidis fell into two groups. The first group of mutations affected Hb
      binding and were located in putative extracellular loops (L) L2 (amino acid
      residues (aa) 192-230) and L3 (aa 254-284). The second group of mutations
      resulted in a failure to utilize Hb but proficiency in Hb binding was retained.
      These mutations localized to the putative extracellular loops L6 (aa 420-462) and
      L7 (aa 486-516). A highly conserved protein motif found in all haem/Hb receptors,
      within putative extracellular loop L7 of HmbR, is essential for Hb utilization
      but not required for Hb binding. This finding suggests a mechanistic involvement
      of this motif in haem removal from Hb. In addition, an amino-terminal deletion in
      the putative cork-like domain of HmbR affected Hb usage but not Hb binding. This
      result supports a role of the cork domain in utilization steps that are
      subsequent to Hb binding.

PMID- 14663077
TI  - PepN is the major aminopeptidase in Escherichia coli: insights on substrate
      specificity and role during sodium-salicylate-induced stress.
AB  - PepN and its homologues are involved in the ATP-independent steps (downstream
      processing) during cytosolic protein degradation. To obtain insights into the
      contribution of PepN to the peptidase activity in Escherichia coli, the
      hydrolysis of a selection of endopeptidase and exopeptidase substrates was
      studied in extracts of wild-type strains and two pepN mutants, 9218 and
      DH5alphaDeltapepN. Hydrolysis of three of the seven endopeptidase substrates
      tested was reduced in both pepN mutants. Similar studies revealed that hydrolysis
      of 10 of 14 exopeptidase substrates studied was greatly reduced in both pepN
      mutants. This decreased ability to cleave these substrates is pepN-specific as
      there is no reduction in the ability to hydrolyse exopeptidase substrates in E.
      coli mutants lacking other peptidases, pepA, pepB or pepE. PepN overexpression
      complemented the hydrolysis of the affected exopeptidase substrates. These
      results suggest that PepN is responsible for the majority of aminopeptidase
      activity in E. coli. Further in vitro studies with purified PepN revealed a
      preference to cleave basic and small amino acids as aminopeptidase substrates.
      Kinetic characterization revealed the aminopeptidase cleavage preference of E.
      coli PepN to be Arg>Ala>Lys>Gly. Finally, it was shown that PepN is a negative
      regulator of the sodium-salicylate-induced stress in E. coli, demonstrating a
      physiological role for this aminoendopeptidase under some stress conditions.

PMID- 14663078
TI  - The LysR-type transcriptional regulator CysB controls the repression of hslJ
      transcription in Escherichia coli.
AB  - The LysR-type transcriptional regulator (LTTR) CysB is a transcription factor in
      Escherichia coli cells, where as a homotetramer it binds the target promoter
      regions and activates the genes involved in sulphur utilization and sulphonate
      sulphur metabolism, while negatively autoregulating its own transcription. The
      hslJ gene was found to be negatively regulated by CysB and directly correlated
      with novobiocin resistance of the bacterium. cysB mutants showed upregulation of
      the hslJ : : lacZ gene fusion and exhibited increased novobiocin resistance. In
      this study the hslJ transcription start point and the corresponding putative
      sigma(70) promoter were determined. The hslJ promoter region was defined by
      employing different hslJ-lacZ operon fusions, and transcription of the hslJ gene
      was shown to be subject to both repression imposed by the CysB regulator and
      direct or indirect autogenous negative control. These two regulations compete to
      some extent but they are not mutually exclusive. CysB acts as a direct repressor
      of hslJ transcription and binds the hslJ promoter region that carries the
      putative CysB repressor site. This CysB binding, apparently responsible for
      repression, is enhanced in the presence of the ligand N-acetylserine (NAS),
      hitherto considered to be a positive cofactor in CysB-mediated gene regulations.
      Interallelic complementation of characterized CysB mutants I33N and S277Ter
      partially restored the repression of hslJ transcription and the consequent
      novobiocin sensitivity, but did not complement the cysteine auxotrophy.

PMID- 14663079
TI  - Pathways for phosphatidylcholine biosynthesis in bacteria.
AB  - Phosphatidylcholine (PC) is the major membrane-forming phospholipid in eukaryotes
      with important structural and signalling functions. Although many prokaryotes
      lack PC, it can be found in significant amounts in membranes of rather diverse
      bacteria. Two pathways for PC biosynthesis are known in bacteria, the methylation
      pathway and the phosphatidylcholine synthase (PCS) pathway. In the methylation
      pathway, phosphatidylethanolamine is methylated three times to yield PC, in
      reactions catalysed by one or several phospholipid N-methyltransferases (PMTs).
      In the PCS pathway, choline is condensed directly with CDP-diacylglyceride to
      form PC in a reaction catalysed by PCS. Using cell-free extracts, it was
      demonstrated that Sinorhizobium meliloti, Agrobacterium tumefaciens, Rhizobium
      leguminosarum, Bradyrhizobium japonicum, Mesorhizobium loti and Legionella
      pneumophila have both PMT and PCS activities. In addition, Rhodobacter
      sphaeroides has PMT activity and Brucella melitensis, Pseudomonas aeruginosa and
      Borrelia burgdorferi have PCS activities. Genes from M. loti and L. pneumophila
      encoding a Pmt or a Pcs activity and the genes from P. aeruginosa and Borrelia
      burgdorferi responsible for Pcs activity have been identified. Based on these
      functional assignments and on genomic data, one might predict that if bacteria
      contain PC as a membrane lipid, they usually possess both bacterial pathways for
      PC biosynthesis. However, important pathogens such as Brucella melitensis, P.
      aeruginosa and Borrelia burgdorferi seem to be exceptional as they possess only
      the PCS pathway for PC formation.

PMID- 14663080
TI  - Attachment to and biofilm formation on abiotic surfaces by Acinetobacter
      baumannii: involvement of a novel chaperone-usher pili assembly system.
AB  - Acinetobacter baumannii causes severe infections in compromised patients,
      survives on abiotic surfaces in hospital environments and colonizes different
      medical devices. In this study the analysis of the processes involved in surface
      attachment and biofilm formation by the prototype strain 19606 was initiated.
      This strain attaches to and forms biofilm structures on plastic and glass
      surfaces, particularly at the liquid-air interface of cultures incubated
      stagnantly. The cell aggregates, which contain cell stacks separated by water
      channels, formed under different culture conditions and were significantly
      enhanced under iron limitation. Electron and fluorescence microscopy showed that
      pili and exopolysaccharides are part of the cell aggregates formed by this
      strain. Electron microscopy of two insertion derivatives deficient in attachment
      and biofilm formation revealed the disappearance of pili-like structures and DNA
      sequencing analysis showed that the transposon insertions interrupted genes with
      the highest similarity to hypothetical genes found in Pseudomonas aeruginosa,
      Pseudomonas putida and Vibrio parahaemolyticus. Although the products of these
      genes, which have been named csuC and csuE, have no known functions, they are
      located within a polycistronic operon that includes four other genes, two of
      which encode proteins related to chaperones and ushers involved in pili assembly
      in other bacteria. Introduction of a copy of the csuE parental gene restored the
      adherence phenotype and the presence of pili on the cell surface of the csuE
      mutant, but not that of the csuC derivative. These results demonstrate that the
      expression of a chaperone-usher secretion system, some of whose components appear
      to be acquired from unrelated sources, is required for pili formation and the
      concomitant attachment to plastic surfaces and the ensuing formation of biofilms
      by A. baumannii cells.

PMID- 14663081
TI  - A polyketide synthase gene required for ochratoxin A biosynthesis in Aspergillus
      ochraceus.
AB  - Ochratoxin A is an important nephrotoxic and nephrocarcinogenic mycotoxin,
      produced by Aspergillus ochraceus as a polyketide-derived secondary metabolite. A
      portion of a putative polyketide synthase gene (pks) involved in the biosynthesis
      of this mycotoxin was cloned by using a suppression subtractive hybridization PCR
      based approach. The predicted amino acid sequence of the 1.4 kb clone shared 28
      35 % identity to acyl transferase regions from fungal polyketide synthases found
      in the databases. Based on reverse transcription PCR studies, the pks gene is
      expressed only under ochratoxin A permissive conditions and only during the early
      stages of the mycotoxin synthesis. A mutant in which the pks gene has been
      interrupted cannot synthesize ochratoxin A. This report is the first of the
      cloning and characterization of a gene involved in ochratoxin A biosynthesis.

PMID- 14663082
TI  - Phage display reveals 52 novel extracellular and transmembrane proteins from
      Lactobacillus reuteri DSM 20016(T).
AB  - Extracellular and transmembrane proteins are important for the binding of
      bacteria to intestinal surfaces and for their interaction with the host. The aim
      of this study was to identify genes encoding extracellular and transmembrane
      proteins from the probiotic bacterium Lactobacillus reuteri by construction and
      screening of a phage display library. This library was constructed by insertion
      of randomly fragmented DNA from L. reuteri into the phagemid vector pG3DSS, which
      was previously developed for screening for extracellular proteins. After affinity
      selection of the library, the L. reuteri inserts were sequenced and analysed with
      bioinformatic tools. The screening resulted in the identification of 52 novel
      genes encoding extracellular and transmembrane proteins. These proteins were
      classified as: transport proteins; enzymes; sensor-regulator proteins; proteins
      involved in host/microbial interactions; conserved hypothetical proteins; and
      unconserved hypothetical proteins. Further characterization of the extracellular
      and transmembrane proteins identified should contribute to the understanding of
      the probiotic properties of L. reuteri.

PMID- 14663083
TI  - Extracting phylogenetic information from whole-genome sequencing projects: the
      lactic acid bacteria as a test case.
AB  - The availability of an ever increasing number of complete genome sequences of
      diverse prokaryotic taxa has led to the introduction of novel approaches to infer
      phylogenetic relationships among bacteria. In the present study the sequences of
      the 16S rRNA gene and nine housekeeping genes were compared with the fraction of
      shared putative orthologous protein-encoding genes, conservation of gene order,
      dinucleotide relative abundance and codon usage among 11 genomes of species
      belonging to the lactic acid bacteria. In general there is a good correlation
      between the results obtained with various approaches, although it is clear that
      there is a stronger phylogenetic signal in some data sets than in others, and
      that different parameters have different taxonomic resolutions. It appears that
      trees based on different kinds of information derived from whole-genome
      sequencing projects do not provide much additional information about the
      phylogenetic relationships among bacterial taxa compared to more traditional
      alignment-based methods. Nevertheless, it is expected that the study of these
      novel forms of information will have its value in taxonomy, to determine which
      genes are shared, when genes or sets of genes were lost in evolutionary history,
      to detect the presence of horizontally transferred genes and/or confirm or
      enhance the phylogenetic signal derived from traditional methods. Although these
      conclusions are based on a relatively small data set, they are largely in
      agreement with other studies and it is anticipated that similar trends will be
      observed when comparing other genomes.

PMID- 14663084
TI  - Mitochondrial-type iron-sulfur cluster biosynthesis genes (IscS and IscU) in the
      apicomplexan Cryptosporidium parvum.
AB  - Several reports have indicated that the iron-sulfur cluster [Fe-S] assembly
      machinery in most eukaryotes is confined to the mitochondria and chloroplasts.
      The best-characterized and most highly conserved [Fe-S] assembly proteins are a
      pyridoxal-5'-phosphate-dependent cysteine desulfurase (IscS), and IscU, a protein
      functioning as a scaffold for the assembly of [Fe-S] prior to their incorporation
      into apoproteins. In this work, genes encoding IscS and IscU homologues have been
      isolated and characterized from the apicomplexan parasite Cryptosporidium parvum,
      an opportunistic pathogen in AIDS patients, for which no effective treatment is
      available. Primary sequence analysis (CpIscS and CpIscU) and phylogenetic studies
      (CpIscS) indicate that both genes are most closely related to mitochondrial
      homologues from other organisms. Moreover, the N-terminal signal sequences of
      CpIscS and CpIscU predicted in silico specifically target green fluorescent
      protein to the mitochondrial network of the yeast Saccharomyces cerevisiae.
      Overall, these findings suggest that the previously identified mitochondrial
      relict of C. parvum may have been retained by the parasite as an intracellular
      site for [Fe-S] assembly.

PMID- 14663085
TI  - Involvement of DivIVA in the morphology of the rod-shaped actinomycete
      Brevibacterium lactofermentum.
AB  - In Brevibacterium lactofermentum, as in many Gram-positive bacteria, a divIVA
      gene is located downstream from the dcw cluster of cell-division- and cell-wall
      related genes. This gene (divIVA(BL)) is mostly expressed during exponential
      growth, and the protein encoded, DivIVA(BL,) bears some sequence similarity to
      antigen 84 (Ag84) from mycobacteria and was detected with monoclonal antibodies
      against Ag84. Disruption experiments using an internal fragment of the divIVA(BL)
      gene or a disrupted divIVA(BL) cloned in a suicide conjugative plasmid were
      unsuccessful, suggesting that the divIVA(BL) gene is needed for cell viability in
      BREV: lactofermentum. Transformation of BREV: lactofermentum with a multicopy
      plasmid containing divIVA(BL) drastically altered the morphology of the
      corynebacterial cells, which became larger and bulkier, and a GFP fusion to
      DivIVA(BL) mainly localized to the ends of corynebacterial cells. This
      localization pattern, together with the overproduction phenotype, suggests that
      DivIVA may be important in regulating the apical growth of daughter cells.

PMID- 14663086
TI  - Co-ordination of iron acquisition, iron porphyrin chelation and iron
      protoporphyrin export via the cytochrome c biogenesis protein CcmC in Pseudomonas
      fluorescens.
AB  - The cytoplasmic membrane protein CcmC is, together with other Ccm proteins, a
      component for the maturation of c-type cytochromes in Gram-negative bacteria. A
      Pseudomonas fluorescens ATCC 17400 ccmC mutant is cytochrome c-deficient and
      shows considerably reduced production of the two siderophores pyoverdine and
      quinolobactin, paralleled by a general inability to utilize various iron sources,
      with the exception of haem. The ccmC mutant accumulates in a 5-aminolevulinic
      acid-dependent synthesis a reddish, fluorescent pigment identified as
      protoporphyrin IX. As a consequence a visA phenotype similar to that of a
      ferrochelatase-deficient hemH mutant characterized by drastically reduced growth
      upon light exposure was observed for the ccmC mutant. The defect of iron
      protoporphyrin formation was further demonstrated by the failure of ccmC cell
      free proteinase K-treated extracts to stimulate the growth of a haem auxotrophic
      hemH indicator strain, compared to similarly prepared wild-type extracts. In
      addition, the ccmC mutant did not sustain hemH growth in cross-feeding
      experiments while the wild-type did. Significantly reduced resistance to
      oxidative stress mediated by haem-containing catalases was observed for the ccmC
      mutant. A double hemH ccmC mutant could not be obtained in the presence of
      external haem without the hemH gene in trans, indicating that the combination of
      the two mutations is lethal. It was concluded that CcmC, apart from its known
      function in cytochrome c biogenesis, plays a role in haem biosynthesis. A
      function in the regulatory co-ordination of iron acquisition via siderophores,
      iron insertion into porphyrin via ferrochelatase and iron-protoporphyrin export
      for cytochrome c formation is predicted.

PMID- 14663087
TI  - Compaction of the Escherichia coli nucleoid caused by Cyt1Aa.
AB  - Compaction of the Escherichia coli nucleoid in the cell's centre was associated
      with the loss of colony-forming ability; these effects were caused by induction
      of Cyt1Aa, the cytotoxic 27 kDa protein from Bacillus thuringiensis subsp.
      israelensis. Cyt1Aa-affected compaction of the nucleoids was delayed but
      eventually more intense than compaction caused by chloramphenicol. The
      possibility that small, compact nucleoids in Cyt1Aa-expressing cells resulted in
      DNA replication run-out and segregation following cell division was ruled out by
      measuring relative nucleoid length. Treatments with membrane-perforating
      substances other than Cyt1Aa did not cause such compaction of the nucleoids, but
      rather the nucleoids overexpanded to occupy nearly all of the cell volume. These
      findings support the suggestion that, in addition to its perforating ability,
      Cyt1Aa causes specific disruption of nucleoid associations with the cytoplasmic
      membrane. In situ immunofluorescence labelling with Alexa did not demonstrate a
      great amount of Cyt1Aa associated with the membrane. Clear separation between
      Alexa-labelled Cyt1Aa and 4',6-diamidino-2-phenylindole (DAPI)-stained DNA
      indicates that the nucleoid does not bind Cyt1Aa. Around 2 h after induction,
      nucleoids in Cyt1Aa-expressing cells started to decompact and expanded to fill
      the whole cell volume, most likely due to partial cell lysis without massive
      peptidoglycan destruction.

PMID- 14663088
TI  - Gradual evolution in bacteria: evidence from Bacillus systematics.
AB  - The bacterial genome projects have suggested a central role for horizontal
      transfer in bacterial adaptation, but it is difficult to rule out an adaptive
      role for ordinary genetic change in existing genes. The bacterial systematics
      literature can readily address the importance of gene acquisition in adaptive
      evolution, since phenotypic characterization typically assesses presence versus
      absence of metabolic capabilities, and metabolic gains and losses are most likely
      due to horizontal transfer and/or gene loss. Bacterial systematists have not
      geared their studies toward quantitative differences in metabolic capabilities,
      which are more likely to involve adjustments of existing genes. Here,
      quantitative variation in metabolism within and between three closely related
      Bacillus taxa has been assayed. While these taxa show no qualitative (i.e.
      presence versus absence) differences in resource utilization, they are
      quantitatively different in utilization of 8 % of 95 resources tested. Moreover,
      93 % of the resources tested showed significant quantitative variation among
      strains within a single taxon. These results suggest that ordinary genetic
      changes in existing genes may play an important role in adaptation. If these
      results are typical, future genomically based assays of quantitative variation in
      phenotype (e.g. microarray analysis of mRNA concentrations) may identify hundreds
      of genes whose expression has been modified. A protocol is presented for
      identifying those modifications of gene expression and those gene acquisitions
      that are most likely to have played a role in adaptive evolution.

PMID- 14663089
TI  - The distribution and genetic structure of Escherichia coli in Australian
      vertebrates: host and geographic effects.
AB  - Escherichia coli was isolated from more than 2300 non-domesticated vertebrate
      hosts living in Australia. E. coli was most prevalent in mammals, less prevalent
      in birds and uncommon in fish, frogs and reptiles. Mammals were unlikely to
      harbour E. coli if they lived in regions with a desert climate and less likely to
      have E. coli if they lived in the tropics than if they lived in semi-arid or
      temperate regions. In mammals, the likelihood of isolating E. coli from an
      individual depended on the diet of the host and E. coli was less prevalent in
      carnivores than in herbivores or omnivores. In both birds and mammals, the
      probability of isolating E. coli increased with the body mass of the host. Hosts
      living in close proximity to human habitation were more likely to harbour E. coli
      than hosts living away from people. The relative abundance of E. coli groups A,
      B1, B2 and D strains in mammals depended on climate, host diet and body mass.
      Group A strains were uncommon, but were isolated from both ectothermic and
      endothermic vertebrates. Group B1 strains could also be isolated from any
      vertebrate group, but were predominant in ectothermic vertebrates, birds and
      carnivorous mammals. Group B2 strains were unlikely to be isolated from
      ectotherms and were most abundant in omnivorous and herbivorous mammals. Group D
      strains were rare in ectotherms and uncommon in endotherms, but were equally
      abundant in birds and mammals. The results of this study suggest that, at the
      species level, the ecological niche of E. coli is mammals with hindgut
      modifications to enable microbial fermentation, or in the absence of a modified
      hindgut, E. coli can only establish a population in 'large-bodied' hosts. The non
      random distribution of E. coli genotypes among the different host groups
      indicates that strains of the four E. coli groups may differ in their ecological
      niches and life-history characteristics.

PMID- 14663090
TI  - A functional plasmid-borne rrn operon in soil isolates belonging to the genus
      Paracoccus.
AB  - Plasmid analysis of isolates from a small Paracoccus population revealed that all
      15 representatives carried at least one endogenous plasmid of 23 or 15 kb in
      size, in addition to further plasmids of different sizes. It was shown by
      restriction analysis and hybridization that the 23 and 15 kb plasmids from the
      different isolates were identical or very similar to each other. By partial
      sequencing of pOL18/23, one of the 23 kb plasmids, a complete rrn operon with the
      structural genes for 16S, 23S and 5S rRNA, two genes for tRNA(Ile) and tRNA(Ala)
      within the spacer between the 16S and 23S rRNA genes, and a final tRNA(fMet) at
      the end of the operon were discovered. Expression of a green fluorescent protein
      gene (gfp) after insertion of a DNA fragment from the region upstream of the rRNA
      genes into a promoter-probe vector demonstrated that the rrn promoter region is
      functional. The rrn operon encoded by plasmid pOL18/23 is the first complete rrn
      operon sequenced from a strain of the genus Paracoccus, and only the second
      example of an rrn operon on a small plasmid.

PMID- 14663091
TI  - A dual lethal system to enhance containment of recombinant micro-organisms.
AB  - Active containment systems based on the controlled expression of a lethal gene
      are designed to increase containment of recombinant micro-organisms used for
      environmental applications. A major drawback in containment is the existence of
      mutations that generate surviving cells that cease to respond to the toxic effect
      of the lethal function. In this work the authors have developed for the first
      time a strategy to reduce the problem of mutations and increase the efficiency of
      containment based on the combination of two lethal functions acting on different
      cellular targets of major concern in containment, DNA and RNA, and whose
      expression is under control of different regulatory signals. To engineer the dual
      gene containment circuit, two toxin-antitoxin pairs, i.e. the colicin E3-immunity
      E3 and the EcoRI restriction-modification systems, were combined. The genes
      encoding the immunity E3 and the EcoRI methyltransferase proteins (antitoxins)
      were stably inserted into the chromosome of the host cell, whereas the broad-host
      range lethal genes encoding the colicin E3 RNase and the EcoRI restriction
      endonuclease (toxins) were flanking the contained trait in a plasmid. This dual
      lethal cassette decreased gene transfer frequencies, through killing of the
      recipient cells, by eight orders of magnitude, which provides experimental
      evidence that the anticipated containment level due to the combination of single
      containment systems is generally achieved. Survivors that escaped killing were
      analysed and the mutational events involved were characterized.

PMID- 14663092
TI  - Variation of the natural transformation frequency of Campylobacter jejuni in
      liquid shake culture.
AB  - Natural transformation, a mechanism that generates genetic diversity in
      Campylobacter jejuni, was studied in a novel liquid shake culturing system that
      allowed an approximately 10 000-fold increase in cell density. C. jejuni
      transformation frequency was analysed in this system under 10 %, 5.0 % and 0.7 %
      CO(2) atmospheres. At 5.0 % and 10 % CO(2) concentrations, when purified isogenic
      chromosomal DNA was used to assess competence, transformation frequency ranged
      from 10(-3) to 10(-4) at low cell concentrations and declined as cell density
      increased. Transformation frequency under a 0.7 % CO(2) atmosphere was more
      stable, maintaining 10(-3) levels at high cell densities, and was 10- to 100-fold
      higher than that under a 10 % CO(2) atmosphere. Three of four C. jejuni strains
      tested under a 5.0 % CO(2) atmosphere were naturally competent for isogenic DNA;
      competent strains demonstrated a lack of barriers to intraspecies genetic
      exchange by taking up and incorporating chromosomal DNA from multiple C. jejuni
      donors. C. jejuni showed a preference for its own DNA at the species level, and
      co-cultivation demonstrated that DNA transfer via natural transformation occurred
      between isogenic populations during short periods of exposure in liquid medium
      when cell density and presumably DNA concentrations were low. Transformation
      frequency during co-cultivation of isogenic populations was also influenced by
      CO(2) concentration. Under a 0.7 % CO(2) atmosphere, co-cultivation
      transformation frequency increased approximately 500-fold in a linear fashion
      with regard to cell density, and was 1000- to 10 000-fold higher during late
      exponential-phase growth when compared to cultures grown under a 10 % CO(2)
      atmosphere.

PMID- 14663093
TI  - The surface (S-) layer is a virulence factor of Bacteroides forsythus.
AB  - Bacteroides forsythus has emerged as a crucial periodontal pathogen with possible
      implications for systemic disease. The aim of this study was to isolate the S
      layer from B. forsythus and examine its virulence potential as a part of efforts
      to characterize virulence factors of B. forsythus. The role of the S-layer in the
      haemagglutinating and adherent/invasive activities was evaluated. It was observed
      that the S-layer alone was able to mediate haemagglutination. In adherent and
      invasive studies, transmission electron microscopy clearly revealed that B.
      forsythus cells were able to attach to and invade KB cells, showing the formation
      of a microvillus-like extension around adherent and intracellular bacteria. The
      quantitative analysis showed that five different B. forsythus strains exhibited
      attachment (1.9-2.3 %) and invasion (0.4-0.7 %) capabilities. It was also
      observed through antibody inhibition assays that adherent/invasive activities of
      B. forsythus are mediated by the S-layer. Furthermore, an in vivo immunization
      study adopting a murine abscess model was used to prove that the S-layer is
      involved in the infectious process of abscess formation. While mice immunized
      with purified S-layer and B. forsythus whole cells did not develop any abscesses
      when challenged with viable B. forsythus cells, unimmunized mice developed
      abscesses. Collectively, the data obtained from these studies indicate that the S
      layer of B. forsythus is a virulence factor.

PMID- 14663094
TI  - Genetic control of chlamydospore formation in Candida albicans.
AB  - The chlamydospore is a distinctive morphological feature of the fungal pathogen
      Candida albicans that can be induced to form in oxygen-limited environments and
      has been reported in clinical specimens. Chlamydospores are not produced by the
      model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, so there is
      limited understanding of the pathways that govern their development. Here, the
      results of a forward genetic approach that begins to define the genetic control
      of chlamydospore formation are described. Six genes - ISW2, MDS3, RIM13, RIM101,
      SCH9 and SUV3 - are required for efficient chlamydospore formation, based on the
      phenotypes of homozygous insertion mutants and reconstituted strains. Mutations
      in ISW2, SCH9 and SUV3 completely abolish chlamydospore formation. Mutations in
      RIM13, RIM101 and MDS3 delay normal chlamydospore formation. The involvement of
      alkaline pH-response regulators Rim13p and Mds3p in chlamydospore formation is
      unexpected in view of the fact that chlamydospores in the inducing conditions
      used here are repressed in alkaline media.

PMID- 14663095
TI  - CesAB is an enteropathogenic Escherichia coli chaperone for the type-III
      translocator proteins EspA and EspB.
AB  - Enteropathogenic Escherichia coli (EPEC) are extracellular pathogens that
      colonize mucosal surfaces of the intestine via formation of attaching and
      effacing (A/E) lesions. The genes responsible for induction of the A/E lesions
      are located on a pathogenicity island, termed the locus of enterocyte effacement
      (LEE), which encodes the adhesin intimin and the type III secretion system needle
      complex, translocator and effector proteins. One of the major EPEC translocator
      proteins, EspA, forms a filamentous conduit along which secreted proteins travel
      before they arrive at the translocation pore in the plasma membrane of the host
      cell, which is composed of EspB and EspD. Prior to secretion, many type III
      proteins, including translocators, are maintained in the bacterial cytoplasm by
      association with a specific chaperone. In EPEC, chaperones have been identified
      for the effector proteins Tir, Map and EspF, and the translocator proteins EspD
      and EspB. In this study, CesAB (Orf3 of the LEE) was identified as a chaperone
      for EspA and EspB. Specific CesAB-EspA and CesAB-EspB protein interactions are
      demonstrated. CesAB was essential for stability of EspA within the bacterial cell
      prior to secretion. Furthermore, a cesAB mutant failed to secrete EspA, as well
      as EspB, to assemble EspA filaments, to induce A/E lesion following infection of
      HEp-2 cells and to adhere to, or cause haemolysis of, erythrocytes.

PMID- 14663096
TI  - The CepIR quorum-sensing system contributes to the virulence of Burkholderia
      cenocepacia respiratory infections.
AB  - The cepIR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum
      sensing system consisting of an AHL synthase that directs the synthesis of N
      octanoyl-L-homoserine lactone (ohl) and n-hexanoyl-L-homoserine lactone and a
      transcriptional regulator. The virulence of cepIR mutants was examined in two
      animal models. Rats were infected with agar beads containing Burkholderia
      cenocepacia K56-2, K56-I2 (cepI : : Tp(r)) or K56-R2 (cepR : : Tn5-OT182). At 10
      days post-infection, the extent of lung histopathological changes was
      significantly lower in lungs infected with K56-I2 or K56-R2 compared to the
      parent strain. Intranasal infections were performed in Cftr((-/-)) mice and their
      wild-type siblings. K56-2 was more virulent in both groups of mice. K56-I2 was
      the least virulent strain and was not invasive in the Cftr((-/-)) mice. OHL was
      readily detected in lung homogenates from Cftr((-/-)) mice infected with K56-2
      but was only detected at levels slightly above background in a few mice infected
      with K56-I2. Lung homogenates from mice infected with K56-2 had significantly
      higher levels of the inflammatory mediators murine macrophage inflammatory
      protein-2, KC/N51, interleukin-1beta and interleukin-6 than those from K56-I2
      infected animals. These studies indicate that a functional CepIR quorum-sensing
      system contributes to the severity of B. cenocepacia infections. A zinc
      metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of
      the factors that accounts for the difference in virulence between the cepI mutant
      and the parent strain.

PMID- 14663098
TI  - Fate of Streptococcus pyogenes and epithelial cells following internalization.
AB  - The fate of GAS and epithelial cells following internalization was determined in
      this study. HEp-2 cells harbouring intracellular bacteria were treated with
      antibiotics to kill extracellular adherent bacteria, washed, and the fate of
      bacteria and epithelial cells was assessed up to 24 h post-infection. In the
      absence of antibiotics, massive bacterial growth was apparent in the cell medium,
      accompanied by extensive cell death, suggesting that intracellular bacteria had
      multiplied and damaged the monolayer. Addition of the internalization inhibitor,
      cytochalasin D, either pre- or post-internalization prevented bacterial growth
      and cell injury; post-internalization treatment with chloramphenicol had the same
      effect. Analysis of three apoptotic markers in HEp-2 cells - chromatin
      condensation, DNA laddering and translocation of phosphatidylserine onto the cell
      surface membrane - indicated that HEp-2 cells underwent apoptosis. Taken
      together, the data presented here support a model in which internalized bacteria
      can induce their own externalization into the medium by a process that requires
      both an intact host-cell cytoskeleton and de novo synthesis of bacterial
      proteins. Concomitantly, intracellular and, apparently, extracellular free
      bacteria induce apoptosis through their cytotoxic activity, and release essential
      nutrients required for their growth.

PMID- 14663099
TI  - Effect of heparin binding on Helicobacter pylori resistance to serum.
AB  - The objective of this study was to evaluate the effect of heparin binding to
      Helicobacter pylori cells on their survival in the presence of fresh rabbit serum
      with or without active complement components. Three H. pylori strains were
      compared and the amounts of heparin added reflected the physiological
      concentrations that can be found in animal tissues. No growth of H. pylori was
      noted in the presence of serum. Serum with or without active complement produced
      a reduction in c.f.u. for strains SPM 326, CCUG 17874(T) and SS1. However,
      addition of heparin resulted in increased survival of bacterial cells in serum
      with or without active complement. It appears that heparin binding to H. pylori
      can prevent bacterial cell death due to the alternative complement system.
      Heparin binding could also protect from heated serum (complement-inactivated),
      indicating protection from other serum components besides complement. In vivo,
      the process of heparin binding could possibly result in facilitated colonization
      due to a higher survival rate.

PMID- 14663100
TI  - Survey for virulence determinants among Enterococcus faecalis isolated from
      different sources.
AB  - A collection of Enterococcus faecalis strains from clinical isolates, healthy
      individuals and the environment was screened for the presence of virulence factor
      genes, such as those for collagen-binding protein (ace), endocarditis antigen
      (efaA), haemolysin activator (cylA), gelatinase (gelE), aggregation substances
      (asa1 and asa373), a surface protein (esp) and two novel putative surface
      antigens (EF0591 and EF3314). Apart from some genes that were present in all
      strains (ace, efaA and EF3314), the gelE gene was the most common factor,
      although its presence did not correlate with its expression. The genes that
      encode Esp and CylA were never detected in endocarditis isolates, whereas an
      association was noted between the esp gene and isolates from urinary tract
      infection (UTI) and bacteraemia. An aggregation substance gene was always present
      in commensal strains. As for gelatinase, the presence of the cylA and asa genes
      did not correlate completely with their phenotypic expression. Generally,
      isolates from endocarditis, biliary stents and the environment were equipped with
      fewer virulence factors than isolates from other sources. UTI strains possessed
      the highest number of factors.

PMID- 14663101
TI  - Immune response in Helicobacter pylori-induced low-grade gastric-mucosa
      associated lymphoid tissue (MALT) lymphoma.
AB  - We have reported previously that heat-shock protein 60 kDa (hsp60) of
      Helicobacter pylori is an important antigen in the pathogenesis of gastric mucosa
      associated lymphoid tissue (MALT) lymphoma. In order to investigate associations
      with host immune reactions and hsp60 antigen, CD40 ligand (CD40L) expression and
      cytokine production were analysed following stimulation with hsp60. To provide a
      clear antigen-driven immune response, peripheral blood mononuclear cells (PBMC)
      from patients with low-grade MALT lymphoma and gastritis and those from healthy
      volunteers were stimulated with recombinant H. pylori hsp60 and H. pylori cell
      lysate in the presence of cytokines (IL4 and granulocyte-macrophage colony
      stimulating factor). mRNA expression was also analysed by a cDNA microarray
      containing 1100 genes. Expression of CD40L on PBMCs of patients with MALT
      lymphoma was increased by cytokines or by combination with stimulation with hsp60
      antigens. The production of IL4 in PBMC cultures was increased in patients with
      MALT lymphoma; however, production of IFN-gamma was at low levels. DNA microarray
      analysis indicated increased levels of HLA-DR and integrin mRNAs. In cases of low
      grade MALT lymphoma, adaptive immune responses against hsp60 may be enhanced by
      host factors, such as antigen presentation and T-cell activation, resulting in B
      cell proliferation, which can be demonstrated during chronic H. pylori infection.

PMID- 14663102
TI  - Production of anti-Helicobacter pylori urease-specific immunoglobulin in egg yolk
      using an antigenic epitope of H. pylori urease.
AB  - The potential therapeutic effects of Helicobacter pylori-specific immunoglobulin
      (IgY-Hp) derived from egg yolk and identification of the immunodominant H. pylori
      proteins have previously been reported. In this study, the urease epitope that is
      recognized by IgY-Hp was identified and used as an immunogen to produce urease
      specific IgY (IgY-HpU). Epitope regions were mapped and peptides of selected
      epitope regions were synthesized. The IgY-Hp titre against synthetic peptides was
      evaluated using ELISA analysis. Hens were immunized with synthetic peptides
      conjugated with BSA. Urease activity was quantified by measuring the optical
      density of an indicator dye. Of the five synthetic peptides assayed, a peptide
      representing 15 amino acid residues of UreB (UB-3; aa 396-410, DNDNFRIKRYLSKYT)
      was specifically recognized by the IgY-Hp. Immunization of hens with BSA
      conjugated UB-3 resulted in the generation of IgY-HpU. IgY-HpU markedly reduced
      H. pylori urease activity by 80 % as compared to control IgY (IgY-BSA). The
      availability of the synthetic UreB-derived peptide enabled the production of
      highly specific anti-urease IgY, which had a significant inhibitory effect on H.
      pylori urease activity. Therefore, specific IgY-HpU produced using the synthetic
      peptide may be an effective tool against infection by H. pylori.

PMID- 14663103
TI  - Identification and interrogation of highly informative single nucleotide
      polymorphism sets defined by bacterial multilocus sequence typing databases.
AB  - A unified, bioinformatics-driven, single nucleotide polymorphism (SNP)-based
      approach to microbial genotyping has been developed. Multilocus sequence typing
      (MLST) databases consist of known variants of standardized housekeeping genes.
      Normally, seven fragments are defined; a sequence type (ST) consists of the
      variants of these fragments that are found in a particular isolate. A computer
      program that can identify highly informative sets of SNPs in entire MLST
      databases has been constructed. The SNPs either define a particular user
      specified ST or provide a high value for Simpson's index of diversity (D), and
      may thus be generally applicable to that species. SNP sets that are diagnostic
      for Neisseria meningitidis ST-11 and ST-42, and high-D SNP sets for N.
      meningitidis and Staphylococcus aureus, were identified and real-time PCR methods
      to interrogate these SNPs were demonstrated. High-D SNP sets were also identified
      in other MLST databases. This widely applicable approach allows rapid genetic
      fingerprinting of infectious agents.

PMID- 14663104
TI  - Restriction endonuclease patterns of the omp1 gene of reference Chlamydia
      trachomatis strains and characterization of isolates from Cameroonian students.
AB  - Eighteen reference strains of Chlamydia trachomatis were differentiated by omp1
      PCR- and nested PCR-based RFLP analysis, using two restriction digestions, one
      with AluI and the other with the three enzymes HpaII, EcoRI and HinfI. AluI
      digestion allowed the differentiation of 12 different profiles after CT1/CT5 PCR
      and 13 different profiles after the nested PCR. The triple hydrolysis permitted
      the identification of 15 different patterns. In all, 16/18 reference strains were
      clearly identified. These reference patterns were successfully used to genotype
      34 of 35 (28 strains and 7 clinical specimens) samples from infected students,
      collected during a screening programme in Yaounde (Cameroon). Genotypes D, Da, E,
      F, G and J were found. The most prevalent omp1 genotype was E (n = 14; 40 %),
      followed by F (n = 7; 20 %). As RFLP patterns of reference strains are essential
      for typing clinical isolates, they will greatly facilitate C. trachomatis
      characterization in many resource-limited laboratories.

PMID- 14663105
TI  - Isolation and molecular characterization of multiresistant Staphylococcus sciuri
      and Staphylococcus haemolyticus associated with skin and soft-tissue infections.
AB  - The isolation, molecular identification and genotyping of multiresistant
      Staphylococcus sciuri and Staphylococcus haemolyticus from skin and soft-tissue
      infections are reported. Accurate and full identification of three coagulase
      negative staphylococcal isolates was achieved using PCR, while the API STAPH
      method failed to identify an isolate of S. haemolyticus fully. The PCR assay,
      which detects polymorphism in the 16S-23S rRNA spacer region, is shown to be
      potentially useful for rapid and accurate identification of coagulase-negative
      staphylococci. Identical PFGE type and antibiotic-resistance profiles of two
      methicillin-resistant S. haemolyticus isolates in this study suggest the
      existence of a multiresistant community clone.

PMID- 14663106
TI  - Preliminary study on rapid identification of Mycobacterium tuberculosis complex
      isolates by the BD ProbeTec ET system.
AB  - The BD ProbeTec ET system for identification of Mycobacterium tuberculosis
      complex (MTBC) isolates from BACTEC 12B culture vials was evaluated in comparison
      with BACTEC NAP (p-nitro-alpha-acetylamino-beta-hydroxy-propiophenone)
      differentiation. Of 145 mycobacterial isolates tested, comprising 89 MTBC and 56
      non-tuberculous mycobacteria (NTM), BD ProbeTec ET correctly identified 87 MTBC
      and 56 NTM but missed two MTBC. Three NTM were misidentified when NAP was
      incubated at 37 degrees C only. Overall sensitivity, specificity and positive and
      negative predictive values were respectively 97.8, 100, 100 and 96.6 % for the BD
      ProbeTec ET system and 100, 94.6, 96.7 and 94.6 % for NAP.

PMID- 14663107
TI  - Antibacterial activity of the marine sponge constituent cribrostatin 6.
AB  - The antibacterial activity of the nitrogen heterocyclic sponge constituent
      cribrostatin 6 was examined. Cribrostatin 6 was bacteriostatic for a variety of
      Gram-positive species and was bactericidal for the majority of clinical isolates
      of Streptococcus pneumoniae, including penicillin-resistant strains. Minimum
      bactericidal concentration/MIC ratios were < or =2 for 75 % of S. pneumoniae
      clinical isolates. Kill-curve analysis confirmed the bactericidal action of
      cribrostatin 6. Bactericidal activity was rather slow, beginning at 2, 4 or 8 h,
      depending on the strain. The frequency of occurrence of bacterial spontaneous
      mutations to resistance was < or =10(-7). The maximum tolerated dose of
      cribrostatin 6 in mice was 750-1000 micro g kg(-1) day(-1). Cribrostatin 6 is a
      promising lead antibiotic for Gram-positive bacteria, particularly S. pneumoniae,
      a leading cause of infection and mortality worldwide.

PMID- 14663108
TI  - Coagulase-negative staphylococci: clinical, microbiological and molecular
      features to predict true bacteraemia.
AB  - Coagulase-negative staphylococci (CNS) are frequently isolated from blood
      cultures, where they may be only a contaminant or the cause of bacteraemia.
      Determining whether an isolate of CNS represents a true CNS bacteraemia is
      difficult, and there is no single criterion with sufficient specificity. The aim
      of this study was to assess those clinical, microbiological, pathogenic and
      genotypic features that characterize true CNS bacteraemia. Twenty patients having
      two or more blood cultures positive for CNS and 20 patients with only one
      positive blood culture were studied. Significant bacteraemia was defined
      according to clinical and laboratory criteria. Incubation time for blood cultures
      to become positive, macroscopic appearance of colonies, species determination,
      biotype, susceptibility to antimicrobials, PFGE pattern and adherence capacity
      were all studied. Clinical bacteraemia was present in 16/20 patients with two or
      more positive blood cultures and in 2/20 patients with only one positive blood
      culture. A significant difference was seen in the median time to positivity
      between the 18 clinical bacteraemias and 22 contaminations (23.6 versus 29.2 h; P
      = 0.04, Wilcoxon). There was also a significant difference between the two groups
      in the median absorbance of the slime test (1.36 versus 0.58; P = 0.005). All
      significant bacteraemias with two or more positive blood cultures had the same
      species identified, the same antimicrobial susceptibility pattern and the same
      PFGE pattern. In two patients with true bacteraemia with only one positive blood
      culture, the incubation time for the culture to turn positive was <24 h and the
      slime production absorbance was >2.5. The most useful parameters for the
      diagnosis of true CNS bacteraemia for patients with two positive blood cultures
      were incubation time until positive, species identification, antimicrobial
      susceptibility pattern, slime production and PFGE pattern. For patients with only
      one blood culture positive for CNS, the useful parameters for prediction of true
      bacteraemia were incubation time until positive and slime production, both of
      which are simple, low-cost tests.

PMID- 14663109
TI  - Genetic features of Pseudomonas aeruginosa isolates from cystic fibrosis patients
      compared with those of isolates from other origins.
AB  - In order to improve our understanding of the colonization of the pulmonary tract
      of cystic fibrosis (CF) patients by Pseudomonas aeruginosa, 162 isolates from
      five different ecological origins were studied. The genetic features of each
      isolate were determined by random amplification of polymorphic DNA (RAPD) and by
      searching for eight virulence genes (six known virulence genes, algD, lasB, toxA,
      plcH, plcN and exoS, and two genes encoding putative neuraminidases, nan1 and
      nan2). Five RAPD groups were identified. Most of the CF isolates were distributed
      equally in three of these groups (RA, RB and RC). The CF isolates in RB were
      related to isolates from a wide variety of origins. The CF isolates in RA were
      related to a population composed of 65 % of the non-CF isolates from pulmonary
      tract infections. RC was mainly composed of CF isolates that were related to 30 %
      of isolates from plants. All genes except exoS and nan1 were present in all
      isolates. The exoS and nan1 virulence factor genes were most prevalent in CF
      isolates. exoS, which encodes exoenzyme S, was present in 94 % of CF isolates but
      also in 80 % of non-CF isolates from pulmonary tract infections. nan1, which
      encodes a putative neuraminidase, was found in 82.5 % of the isolates from group
      RC, which was composed largely of CF isolates. In conclusion, three major
      genogroups of P. aeruginosa isolates, each of which exhibits peculiar genetic
      features, are able to colonize CF patients. This may have different consequences
      on the outcome of pulmonary disease.

PMID- 14663110
TI  - Severe community-acquired pneumococcal pneumonia (CAP) - a potentially fatal
      illness.
AB  - Two cases of severe community-acquired pneumococcal pneumonia (CAP) admitted to
      our hospital within 24 h are described, both in young males. These two cases
      illustrate the usefulness of the British Thoracic Society severity criteria and
      serve to emphasize the importance of early recognition of adverse physiology in
      critically ill patients. We should not lose sight of the continued impact of
      pneumonia in this climate of widespread fear about severe acute respiratory
      syndrome (SARS).

PMID- 14663111
TI  - Molecular epidemiology of emerging reduced susceptibility to fluoroquinolones in
      Escherichia coli.

PMID- 14663113
TI  - Sexually transmitted infections in Africa: single dose treatment is now
      affordable.

PMID- 14663115
TI  - STI services in the United Kingdom: how shall we cope?

PMID- 14663116
TI  - STI services in the United Kingdom: a way forward.

PMID- 14663117
TI  - HIV testing attitudes, AIDS stigma, and voluntary HIV counselling and testing in
      a black township in Cape Town, South Africa.
AB  - OBJECTIVES: A cornerstone of HIV prevention in South Africa is voluntary HIV
      antibody counselling and testing (VCT), but only one in five South Africans aware
      of VCT have been tested. This study examined the relation between HIV testing
      history, attitudes towards testing, and AIDS stigmas. METHODS: Men (n = 224) and
      women (n = 276) living in a black township in Cape Town completed venue intercept
      surveys; 98% were black, 74% age 35 or younger. RESULTS: 47% of participants had
      been tested for HIV. Risks for exposure to HIV were high and comparable among
      people tested and not tested. Comparisons on attitudes toward VCT, controlling
      for demographics and survey venue, showed that individuals who had not been
      tested for HIV and those tested but who did not know their results held
      significantly more negative testing attitudes than individuals who were tested,
      particularly people who knew their test results. Compared to people who had been
      tested, individuals who were not tested for HIV demonstrated significantly
      greater AIDS related stigmas; ascribing greater shame, guilt, and social
      disapproval to people living with HIV. Knowing test results among those tested
      was not related to stigmatising beliefs. CONCLUSIONS: Efforts to promote VCT in
      South Africa require education about the benefits of testing and, perhaps more
      important, reductions in stigmatising attitudes towards people living with AIDS.
      Structural and social marketing interventions that aim to reduce AIDS stigmas
      will probably decrease resistance to seeking VCT.

PMID- 14663118
TI  - A pilot study to evaluate the safety and feasibility of the administration of
      AZT/3TC fixed dose combination to HIV infected pregnant women and their infants
      in Rio de Janeiro, Brazil.
AB  - OBJECTIVES: To evaluate the safety and feasibility of zidovudine and lamivudine
      (AZT/3TC) given to HIV infected pregnant women and their infants in Rio de
      Janeiro, Brazil. METHODS: This open label phase II study enrolled 40 HIV infected
      antiretroviral naive women >or=20 weeks gestation, CD4 <500 cells x10(6)/l, from
      two public hospitals. TREATMENT: fixed dose AZT 300 mg/3TC 150 mg by mouth every
      12 hours until labour; AZT 300 mg by mouth every 3 hours until delivery; infants:
      AZT 4 mg/kg every 12 hours plus 3TC 2 mg/kg every 12 hours for 6 weeks. Blood
      haematology and chemistry were monitored; adherence evaluated by pills count;
      efficacy measured by changes in lymphocyte (CD4) and viral load, and by HIV RNA
      PCR tests performed at birth, 6 and 12 weeks, to diagnose infant infection. No
      women breast fed. RESULTS:  PATIENT CHARACTERISTICS: mean age 24.48 (SD 3.5)
      years; gestational age 24.5 (4.5) weeks; AZT/3TC duration 14.4 (4.4) weeks;
      vaginal delivery: 11/39; caesarean section: 28/39. Entry and pre-labour CD4:
      310/486 cells x10(6)/l (p<0.001); entry and pre-labour viral load: 53 818/2616
      copies/ml (p<0.001). Thirty nine women tolerated treatment with >80% adherence;
      one was lost to follow up. Five newborns were excluded from 3TC receipt. All 39
      babies were uninfected. Haematological toxicity in newborns was common: anaemia
      in 27; neutropenia in five (two severe); platelets counts <100000 in two. All
      values recovered on study completion. CONCLUSIONS: Fixed dose AZT/3TC is well
      accepted, gives improvements in CD4 and viral load; no infants were HIV infected.
      Haematological toxicity in infants needs careful monitoring.

PMID- 14663119
TI  - Unusual presentation of early lymphogranuloma venereum in an HIV-1 infected
      patient: effective treatment with 1 g azithromycin.
AB  - The incidence of lymphogranuloma venereum (LGV) is low in the western world.
      Early LGV is characterised by bubonic disease following a painless papule or
      small ulcer. We report a white bisexual male who presented with a painful
      perianal ulcer, inguinal lymphadenitis, and concomitant infection with human
      immunodeficiency virus 1 (HIV-1). Chlamydia trachomatis serovar L2 was identified
      as the cause after polymerase chain reaction and genotyping the major outer
      membrane protein by restricted fragment length polymorphism. Treatment with a
      single dose of 1 g azithromycin was effective. This case illustrates that early
      LGV may mimic other genital ulcer diseases, such as genital herpes or chancroid,
      especially in HIV infected patients. In the western world, LGV must still be
      included in the differential diagnosis of bubonic disease with or without
      sexually acquired ulcers.

PMID- 14663120
TI  - Epidemiology of recurrent genital herpes simplex virus types 1 and 2.
AB  - OBJECTIVES: To describe the epidemiology of type specific recurrent genital
      herpes, and to compare the duration of recurrent genital lesions caused by herpes
      simplex virus (HSV) types 1 and 2. METHODS: Participants were enrolled at clinics
      across the United States. Adults suspected of having active genital herpes were
      eligible. Lesions were cultured for HSV and typed. Data from 940 participants
      with recurrent culture positive HSV lesions were analysed. Pearson's chi(2) and
      Fisher's exact tests, multivariate logistic regression models, and a stratified
      Cox proportional hazards model were used to compare epidemiological
      characteristics and lesion duration of HSV-1 and HSV-2. RESULTS: HSV-1 was
      present in 4.2% of the recurrent HSV culture positive lesions. HSV-1 was most
      prevalent among whites (6.5%) and individuals with 0-2 recurrences in the
      previous year (9.1%) and, among men, in those with rectal/perirectal lesions
      (13.2%). Longer lesion duration was not significantly associated with virus type
      (hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.65 to 1.38, p = 0.79),
      but was associated with male sex (HR 0.85, 95% CI 0.74 to 0.99, p = 0.04), and
      HIV seropositivity (HR 0.62, 95% CI 0.48 to 0.81, p<0.01). CONCLUSIONS: The
      authors found that, in the United States, recurrent genital HSV-1 is relatively
      rare in the STD and HIV clinic setting, especially among black people. Among men,
      rectal/perirectal recurrent lesions are more likely to be caused by HSV-1 than
      are penile lesions. In addition, lesion duration depends on sex and HIV status
      but not virus type. These findings shed new light on the type specific
      epidemiology of recurrent genital HSV, and suggest that type specific testing can
      inform the prognosis and management of genital herpes.

PMID- 14663121
TI  - A population based study of herpes simplex virus 2 seroprevalence in rural Costa
      Rica.
AB  - OBJECTIVES: To determine seroprevalence and determinants of herpes simplex virus
      2 (HSV-2) seropositivity, in a random sample of a population based cohort of 10
      049 women of Guanacaste, Costa Rica, using a highly sensitive and specific
      serological assay. METHODS: Seroprevalence was determined by a type specific HSV
      2 ELISA assay in an age stratified random sample of 1100 women. Univariate and
      multivariate logistic regression was used to calculate odds ratios and 95%
      confidence intervals for risk factors of seropositivity. RESULTS: Overall age
      adjusted HSV-2 seroprevalence was 38.5% (95% CI, 37.5 to 39.5), and it was
      strongly associated with increasing age (p(Trend<0.0001)), both among monogamous
      women and women with multiple sexual partners. A greater number of lifetime
      sexual partners increased the risk of seropositivity, with a 28.2% (95% CI, 24.4
      to 32.2) seroprevalence among monogamous women and 75% (95% CI, 65.6 to 83.0)
      seroprevalence for those with four or more partners (OR = 7.6 95% CI, 4.7 to 12.4
      p(Trend<0.0001)). Barrier contraceptive use was negatively associated with HSV-2
      seropositivity (OR 0.54, 95% CI, 0.31 to 0.94). Women with antibodies against HPV
      16, 18, or 31 were 1.6 times more likely to be HSV-2 seropositive (OR 1.6, 95%
      CI, 1.2 to 2.1). CONCLUSIONS: HSV-2 infection is highly endemic in Guanacaste,
      even among lifetime monogamous women, suggesting a role of male behaviour in the
      transmission of the infection. Until vaccination against HSV-2 is available,
      education to prevent high risk sexual behaviour and the use of condoms appear as
      preventive measures against HSV-2.

PMID- 14663122
TI  - Associations between internet sex seeking and STI associated risk behaviours
      among men who have sex with men.
AB  - OBJECTIVE: This exploratory study identified associations between internet sex
      seeking and HIV associated risk behaviours among a high risk sample of men who
      have sex with men (MSM). METHODS: A cross sectional survey of men attending a sex
      resort was conducted. Of 164 men asked to participate, 91% completed a self
      administered questionnaire. The questionnaire assessed demographic variables and
      (using a 3 month recall period) men's HIV associated sexual risk behaviours.
      Potential confounding variables were assessed and controlled, as needed, by
      multivariate analysis. RESULTS: Men currently resided in 14 states. One sixth
      reported being HIV positive. 57% of the men reported using the internet to seek
      sex. Differences in critical behaviours (unprotected anal sex and number of
      partners) were not found. However, compared to those not seeking sex by internet,
      men using the internet to meet sex partners were more likely to report fisting
      (adjusted odds ratio = 3.3, p = 0.04), having group sex (prevalence ratio (PR) =
      1.2, p = 0.0001), using poppers during sex (PR = 1.94, p = 0.0001), and using
      ecstasy during sex (PR = 2.7, p = 0.04). Internet sex seeking men were also
      significantly more likely to report meeting sex partners in bathhouses (PR = 2.2,
      p = 0.0001), bars (PR = 1.5, p = 0.001), parks (PR = 3.2, p = 0.006), and circuit
      parties (PR = 8.9, p = 0.007). CONCLUSION: Among MSM attending a sex resort,
      those using the internet to seek sex partners may have modestly elevated risks
      for acquiring or transmitting sexually transmitted infections. Subsequent studies
      should investigate the utility of using the internet as forum for promoting safer
      sex behaviours among high risk MSM.

PMID- 14663123
TI  - High postpartum rates of sexually transmitted infections among teens: pregnancy
      as a window of opportunity for prevention.
AB  - OBJECTIVES: To identify incidence and predictors of Chlamydia trachomatis and
      Neisseria gonorrhoeae among postpartum adolescents. These estimates are compared
      to similar estimates among a cohort of non-pregnant, sexually active teens.
      METHODS: 203 pregnant and 208 non-pregnant adolescents aged 14-19 years were
      recruited from 10 community based health clinics in Connecticut, United States.
      Structured interviews and sexually transmitted infection (STI) testing using
      ligase chain reaction (LCR) were conducted at a baseline visit (during the third
      trimester for the pregnant adolescents), and at 6 and 12 month follow up visits
      (3 and 9 months post partum, for those pregnant at baseline). RESULTS: Among
      pregnant teens, new infections of C trachomatis and N gonorrhoeae increased from
      7.1% at the 6 month follow up interview to 14.3% at the 12 month follow up
      interview; among non-pregnant teens, new infections remained relatively stable
      over the 6 and 12 month follow up interviews (9.0% to 8.3%) (group by time
      interaction, p = 0.005). C trachomatis and N gonorrhoeae prevalence was 1.9 times
      higher (95% CI: 0.97 to 3.89, p = 0.06) among teens in the late postpartum follow
      up compared to the non-pregnant teens, controlling for baseline STIs. Predictors
      of postpartum STIs included having a new partner and number of partners per year
      of sexual activity. CONCLUSIONS: Postpartum adolescents are vulnerable to STIs.
      Routine prenatal and postpartum care provide unique opportunities to promote
      condom use and other risk reduction interventions among adolescents. If sustained
      post partum, long term reproductive health can be promoted.

PMID- 14663124
TI  - Prevalence and determinants of Chlamydia trachomatis infections in women from
      Bogota, Colombia.
AB  - OBJECTIVES: Chlamydia trachomatis infection in the cervix and uterus has been
      hypothesised to be a co-factor for cervical cancer. We performed a cross
      sectional study in Bogota, Colombia, where cervical cancer rates are high, to
      determine the prevalence and determinants of C trachomatis infection, and in
      particular its association with human papillomavirus (HPV). METHODS: 1829 low
      income sexually active women were interviewed and tested for C trachomatis, using
      an endogenous plasmid PCR-EIA, and for 37 HPV types, using a general primer
      GP5+/6+ mediated PCR-EIA. RESULTS: The overall prevalence of C trachomatis was
      5.0%, and it did not differ substantially between women with normal (5.0%) and
      those with abnormal (5.2%) cervical cytology. Women infected with any HPV type
      (15.1%) had a slightly increased risk of being simultaneously infected with C
      trachomatis (adjusted OR 1.3, 95% CI: 0.8 to 2.4). This association was stronger
      when multiple HPV infections (adjusted OR 2.5, 95% CI: 1.1 to 5.9) were present.
      No other lifestyle or reproductive characteristics were clearly associated with
      risk of C trachomatis infection. CONCLUSIONS: HPV infected women, particularly
      women with multiple HPV infections, are at increased risk of being infected with
      C trachomatis.

PMID- 14663125
TI  - Use of PCR in the diagnosis of early syphilis in the United Kingdom.
AB  - OBJECTIVES: To evaluate a Treponema pallidum polymerase chain reaction (PCR) test
      in the laboratory diagnosis of early syphilis in the United Kingdom. SUBJECTS AND
      SETTING: Men and women attending genitourinary medicine clinics in England.
      METHODS: A trial PCR service was offered for the analysis of swabs of ano-genital
      or oral ulcers suspected to be syphilitic in origin. Clinical details, results of
      treponemal serology, and other relevant laboratory tests carried out by the
      sending laboratories were obtained retrospectively by questionnaire. RESULTS:
      Data from 98 patients, representing 100 episodes of ulceration, were analysed.
      The majority of patients (70) attended clinics in the Greater Manchester area.
      Eighty six patients were male and 58 were men who have sex with men (MSM), of
      whom 24 were HIV positive. PCR results agreed with the clinical diagnosis for 95
      patients; samples from 26 patients were PCR positive and serologically diagnosed
      as primary (18) or secondary (8) syphilis, whereas 70 patients had PCR negative
      samples and were not diagnosed as having active syphilis. These data include two
      HIV positive patients who were PCR positive 12 and 21 days before their
      treponemal seroconversion. One positive PCR result was not supported by positive
      treponemal serology (this patient coincidentally received a 10 day course of co
      amoxiclav 1 week after sampling). Three patients had negative PCR results but
      positive syphilis serology. The sensitivity, specificity, positive and negative
      predictive value for primary syphilis were 94.7%, 98.6%, 94.7%, and 98.6%,
      respectively, and for secondary syphilis these were 80.0%, 98.6%, 88.9%, and
      97.2%, respectively. CONCLUSION: PCR is a sensitive and specific test for T
      pallidum, and an important adjunct to dark ground microscopy and treponemal
      serology in diagnosing infectious syphilis in the United Kingdom.

PMID- 14663126
TI  - Evaluation of ligase chain reaction for the non-cultural detection of rectal and
      pharyngeal gonorrhoea in men who have sex with men.
AB  - OBJECTIVES: To compare a nucleic acid amplification test (ligase chain reaction)
      with culture for detecting rectal and pharyngeal gonorrhoea in men who have sex
      with men (MSM). METHODS: Duplicate rectal and throat swabs from MSM attending a
      genitourinary medicine clinic were collected for culture on modified New York
      City medium and detection of gonococcal nucleic acid by the Abbott ligase chain
      reaction (LCR) utilising probes based on opa 1 gene sequences. LCR positive
      culture negative specimens were tested by a second LCR utilising probes based on
      pilin gene sequences. Patients with rectal and/or pharyngeal cultures yielding
      Gram negative diplococci confirmed as Neisseria gonorrhoeae by biochemical and
      immunological methods were diagnosed with rectal and/or pharyngeal gonorrhoea.
      The criteria for diagnosing rectal and pharyngeal infection by LCR included a
      positive opa LCR with a positive culture from the same site or, in the case of a
      negative culture, a positive opa LCR and a positive pilin LCR. RESULTS: Duplicate
      rectal samples were obtained from 227 MSM. The results of LCR and culture were
      concordant in 219 samples (96.5%). The prevalence of rectal gonorrhoea by LCR and
      culture was 7.0% (16/227) and 4.0% (9/227), respectively. Duplicate throat
      samples were obtained from 251 MSM. The results of LCR and culture were
      concordant in 230 (91.6%) cases. The prevalence of pharyngeal gonorrhoea by LCR
      and culture was 12.7% (32/251) and 6.0% (15/251), respectively. The specificity
      of LCR was 99.5% (210/211) for rectal and 98.2% (215/219) for pharyngeal
      specimens. CONCLUSIONS: The high prevalence and asymptomatic nature of pharyngeal
      and rectal gonococcal infection suggests that routine screening for infection at
      these sites by a nucleic acid amplification test method such as LCR should be
      considered as part of the overall strategy to control gonorrhoea in MSM.

PMID- 14663127
TI  - Poor sensitivity and consistency of microscopy in the diagnosis of low grade non
      gonococcal urethritis.
AB  - OBJECTIVES: To determine the reliability of the diagnosis of non-gonococcal
      urethritis (NGU), and the variation between and within microscopists, from
      urethral smears at a large London genitourinary medicine clinic. METHODS: A
      senior microscopist (SM) preselected 60 Gram stained urethral smear slides, 20
      negative (<5 polymorphs/hpf), 20 low grade NGU (5-20 p/hpf), and 20 high grade
      NGU (>20 p/hpf). Ten experienced microscopists, blinded to these initial grades,
      examined all slides giving each a polymorph score. After relabelling and randomly
      changing their order, the slides were re-examined by the same microscopists.
      Finally, the SM determined whether the study had resulted in loss of cells from
      any of the slides. The SM's initial grading and the consensus among microscopists
      provide two gold standards for analysis. RESULTS: Nine low grade and five high
      grade slides were removed from analysis because of loss of cells. By SM standard,
      considering microscopists' readings as simply non-NGU (<5 p/hpf) or NGU (>or=5
      p/hpf), 97% from negative slides were correct (variation 93-100 across
      microscopists), 68% from low grade slides (45-95), and 94% from high grade slides
      (83-100). Consistency between repeat readings by the same microscopist was 96%
      for negatives, 75% for low grade and 89% for high grade slides. Results were
      similar by consensus standard. CONCLUSIONS: There was considerable variation
      between and within microscopists in the diagnosis of NGU. Sensitivity was
      strongly related to grade of urethritis, with an appreciable proportion of low
      grade urethritis falsely diagnosed as negative. With increasing attendances for
      sexual health screening, a false positive rate of only 3% may lead to many false
      diagnoses.

PMID- 14663128
TI  - Diagnosis of pelvic inflammatory disease: time for a rethink.
AB  - OBJECTIVES: To critically evaluate the available evidence base concerned with the
      diagnosis of pelvic inflammatory disease (PID) based on clinical presentation,
      and to investigate the relation between signs and symptoms and the presence of
      laparoscopically diagnosed PID using the largest available dataset. METHODS: The
      evidence base was critically evaluated and data collected by Lund University
      between 1960 and 1969 were used to compare clinical presentation with the results
      of laparoscopic investigation. Three techniques were used in this investigation
      sensitivity and specificity, likelihood ratios, and discriminant analysis.
      RESULTS: None of the variables (abnormal vaginal discharge, fever >38 degrees C,
      vomiting, menstrual irregularity, ongoing bleeding, symptoms of urethritis,
      rectal temperature >38 degrees C, marked tenderness of pelvic organs on bimanual
      examination, adnexal mass, and erythrocyte sedimentation rate >or=15 mm in the
      first hour) had both high specificity and sensitivity-most had low specificity
      and sensitivity. There was little variation in either the likelihood ratios or
      the post-test probabilities between the variables. The lowest likelihood ratio
      (0.97) produced a post-test probability of 78% (95% CI: 74% to 81%) whereas the
      highest (1.73) had a post-test probability of 84% (95% CI: 81% to 87%). The
      pretest probability of having PID based on the presence of lower abdominal pain
      was 79% (95% CI: 76% to 82%). The discriminant analysis indicated that three
      variables significantly influenced the prediction of the presence of PID:
      erythrocyte sedimentation rate (p<0.0001), fever (p<0.0001), and adnexal
      tenderness (p<0.0001). These variables correctly classified 65% of patients with
      laparoscopically diagnosed PID (95% CI: 61% to 69%). CONCLUSION: There is
      insufficient evidence to support existing diagnostic criteria, which have been
      based on a combination of empirical data and expert opinion. A new evidence base
      is urgently needed but this will require either a new investigation of the
      association between clinical presentation and PID based on a laparoscopic "gold
      standard" or the development of new diagnostic techniques.

PMID- 14663129
TI  - HIV and circumcision: new factors to consider.

PMID- 14663130
TI  - Coexistent cranial tuberculomas and tuberculosis of the cervix in a
      postmenopausal woman.

PMID- 14663131
TI  - Seroprevalence of reproductive tract infections in women in northern India-a
      relatively low prevalence area.

PMID- 14663132
TI  - STI case management at a South African teaching hospital.

PMID- 14663133
TI  - Chaperoning in genitourinary medicine supporting patients and protecting doctors.

PMID- 14663134
TI  - Male circumcision in Britain: findings from a national probability sample survey.

PMID- 14663135
TI  - Cutaneous larva migrans of the penis.

PMID- 14663136
TI  - Prevalence of STDs among prostitutes in Czech border areas with Germany in 1997
      2001 assessed in project "Jana".
AB  - BACKGROUND: The STD problem emerged in the Czech Republic as a result of
      geopolitical and social and economic changes in the state. Prostitution is
      concentrated mainly around border areas with Austria and Germany, contributing to
      the increase in STDs. The Czech-German project "Jana," based on a project
      umbrella network of the WHO, was organised. OBJECTIVES: To prevent STDs,
      including HIV/AIDS, and assessment of STD prevalence in the target group.
      METHODS: Prostitutes working in night clubs and in the streets and roads of three
      districts in the West Bohemian Region of the Czech Republic bordering on Germany
      were studied. Interactions included street work, venereology check up, psychology
      and sociology counselling, psychological preparation on possible treatment, and
      continuous and regular contact. RESULTS: The number of "love clubs" involved in
      project "Jana" increased from 46 in 1997 to 72 in 2000. Of 561 street girls
      registered in the project during 1997-2001, there was one HIV positive, every
      11th prostitute had syphilis, and one in 93 women had gonorrhoea, whereas
      incidence of syphilis in the Czech Republic was 10.2/100000 and that of
      gonorrhoea 9.5/100000 inhabitants in 2001, 31 women had Chlamydia trachomatis
      urinary tract and genital infection, and 25 were HBsAg positives. STD frequency
      revealed in project participants significantly exceeds numbers of STDs in the
      other inhabitants of the Czech Republic. The majority of prostitutes were
      foreigners, mostly Ukrainians and Russians. CONCLUSION: The situation in the
      border areas is alarming. The priority must be to concentrate efforts on
      prevention of spread of venereal diseases in borders of economically disparate
      states.

PMID- 14663137
TI  - Motility of dendritic spines in visual cortex in vivo: changes during the
      critical period and effects of visual deprivation.
AB  - Cortical dendritic spines are highly motile postsynaptic structures onto which
      most excitatory synapses are formed. It has been postulated that spine dynamics
      might reflect synaptic plasticity of cortical neurons. To test this hypothesis,
      we have investigated spine dynamics during the critical period in mouse visual
      cortex in vivo with and without sensory deprivation. The motility of spines on
      apical dendrites of layer 5 neurons was assayed by time-lapse two-photon
      microscopy. Spines were motile at the ages examined, postnatal days (P)21-P42,
      although motility decreased between P21 and P28 and then remained stable through
      P42. Binocular deprivation from before the time of eye-opening up-regulated spine
      motility during the peak of the critical period (P28), without affecting average
      spine length, class distribution, or density. Deprivation at the start of the
      critical period had no effect on spine motility, whereas continued deprivation
      through the end of the critical period appeared to reduce spine motility
      slightly. We conclude that spine motility might be involved in critical-period
      plasticity and that reduction of activity during the critical period enhances
      spine dynamics.

PMID- 14663138
TI  - Epstein-Barr virus activates beta-catenin in type III latently infected B
      lymphocyte lines: association with deubiquitinating enzymes.
AB  - beta-Catenin is a multifunctional protein, stabilization of which is a critical
      step in its functional activity. Stabilization can be conferred through several
      means, including mutations in beta-catenin, common in many carcinomas. In this
      article, we explore the effect of viral infection on the beta-catenin signaling
      pathway in B lymphocytes, including cell lines derived from lymphomas. Infection
      by the human tumor virus Epstein-Barr virus (EBV) generates several types of
      latency with different spectra of latent gene expression that are associated with
      different malignancies. In type III latency, exemplified by EBV
      lymphoproliferative diseases, the full range of these viral proteins is
      expressed, whereas in type I latency, only the EBNA1 protein is expressed and
      functional. We show that beta-catenin is rapidly degraded in type I B lymphocytic
      lines but it is stabilized in type III B cell lines, and that beta-catenin/T cell
      factor transcriptional activity is significantly higher in type III cells. Also
      we show the association of free cytoplasmic beta-catenin with deubiquitinating
      enzymes, which may play a role in beta-catenin stabilization. Activation of the
      beta-catenin/T cell factor pathway by EBV may contribute to the
      lymphoproliferation characteristic of type III latency.

PMID- 14663139
TI  - Endonuclease G is required for early embryogenesis and normal apoptosis in mice.
AB  - Endonuclease G (EndoG) is a nuclear-encoded mitochondrial protein reported to be
      important for both nuclear DNA fragmentation during apoptosis and mitochondrial
      DNA replication. To evaluate the in vivo function of EndoG, we have investigated
      the effects of EndoG deficiency in cells and mice. We found that EndoG homozygous
      mutant embryos die between embryonic days 2.5 and 3.5. Mitochondrial DNA copy
      numbers in ovulated oocytes from EndoG heterozygous mutant and wild-type mice are
      similar, suggesting that EndoG is involved in a cellular function unrelated to
      mitochondrial DNA replication. Interestingly, we found that cells from EndoG
      heterozygous mutant mice exhibit increased resistance to both tumor necrosis
      factor alpha- and staurosporine-induced cell death. Moreover, spontaneous cell
      death of spermatogonia in EndoG heterozygous mutant mice is significantly reduced
      compared with wild-type mice. DNA fragmentation is also reduced in EndoG+/-
      thymocytes and splenocytes compared with wild-type cells, as well as in EndoG+/-
      thymus in vivo compared with that of the wild-type mice, on activation of
      apoptosis. These findings indicate that EndoG is essential during early
      embryogenesis and plays a critical role in normal apoptosis and nuclear DNA
      fragmentation.

PMID- 14663140
TI  - Two different Swi5-containing protein complexes are involved in mating-type
      switching and recombination repair in fission yeast.
AB  - Homologous recombination is an important biological process that occurs in all
      organisms and facilitates genome rearrangements and repair of DNA double-strand
      breaks. Eukaryotic Rad51 proteins (Rad51sp or Rhp51 in fission yeast) are
      functional and structural homologs of bacterial RecA protein, an evolutionarily
      conserved protein that plays a key role in homologous pairing and strand exchange
      between homologous DNA molecules in vitro. Here we show that the fission yeast
      swi5+ gene, which was originally identified as a gene required for normal mating
      type switching, encodes a protein conserved among eukaryotes and is involved in a
      previously uncharacterized Rhp51 (Rad51sp)-dependent recombination repair pathway
      that does not require the Rhp55/57 (Rad55/57sp) function. Protein interactions
      with both Swi5 and Rhp51 were found to be mediated by a domain common to Swi2 and
      Sfr1 (Swi five-dependent recombination repair protein 1, a previously
      uncharacterized protein with sequence similarity to the C-terminal part of Swi2).
      Genetic epistasis analyses suggest that the Swi5-Sfr1-Rhp51 interactions function
      specifically in DNA recombination repair, whereas the Swi5-Swi2-Rhp51
      interactions may function, together with chromodomain protein Swi6 (HP1 homolog),
      in mating-type switching.

PMID- 14663141
TI  - Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced
      neuronal cell death.
AB  - Caspase-1 plays a key role in inflammatory pathways by processing pro-IL-1beta
      into the active cytokine mature IL-1beta. Given its sequence similarity with the
      Caenorhabditis elegans cell death gene ced-3,it has long been speculated that
      caspase-1 may also play a role in cell death. However, an unequivocal role for
      caspase-1 in cell death has been questioned, and not definitively demonstrated.
      Furthermore, if caspase-1 does play a role in cell death, its position in the
      apoptotic hierarchy has not been clearly defined. Previous studies have shown
      that caspase-1 knockout (KO) mice and transgenic mice expressing a dominant
      negative caspase-1 construct are resistant to ischemic brain injury. We provide
      direct evidence that caspase-1 plays a key role in neuronal cell death and that
      caspase-1 is an apical activator of the cell death pathway in the
      premitochondrial collapse stage. Furthermore, we demonstrate that
      Rip2/Cardiak/Rick is a stress-inducible upstream modulator of pro-caspase-1
      apoptotic activation. We provide evidence that Bid cleavage appears to be an
      important downstream effector of caspase-1-mediated cell death. Our data
      demonstrate that caspase-1 is an apical mediator of neuronal cell death during in
      vitro hypoxia, and confirmed in vivo in ischemia, and provide insights into the
      sequence of events involved in this pathological cell death process.

PMID- 14663142
TI  - The compositional adjustment of amino acid substitution matrices.
AB  - Amino acid substitution matrices are central to protein-comparison methods. In
      most commonly used matrices, the substitution scores take a log-odds form,
      involving the ratio of "target" to "background" frequencies derived from large,
      carefully curated sets of protein alignments. However, such matrices often are
      used to compare protein sequences with amino acid compositions that differ
      markedly from the background frequencies used for the construction of the
      matrices. Of course, the target frequencies should be adjusted in such cases, but
      the lack of an appropriate way to do this has been a long-standing problem. This
      article shows that if one demands consistency between target and background
      frequencies, then a log-odds substitution matrix implies a unique set of target
      and background frequencies as well as a unique scale. Standard substitution
      matrices therefore are truly appropriate only for the comparison of proteins with
      standard amino acid composition. Accordingly, we present and evaluate a rationale
      for transforming the target frequencies implicit in a standard matrix to
      frequencies appropriate for a nonstandard context. This rationale yields
      asymmetric matrices for the comparison of proteins with divergent compositions.
      Earlier approaches are unable to deal with this case in a fully consistent
      manner. Composition-specific substitution matrix adjustment is shown to be of
      utility for comparing compositionally biased proteins, including those of
      organisms with nucleotide-biased, and therefore codon-biased, genomes or
      isochores.

PMID- 14663143
TI  - Membrane tube formation from giant vesicles by dynamic association of motor
      proteins.
AB  - The tubular morphology of intracellular membranous compartments is actively
      maintained through interactions with motor proteins and the cytoskeleton. Moving
      along cytoskeletal elements, motor proteins exert forces on the membranes to
      which they are attached, resulting in the formation of membrane tubes and tubular
      networks. To study the formation of membrane tubes by motor proteins, we
      developed an in vitro assay consisting of purified kinesin proteins directly
      linked to the lipids of giant unilamellar vesicles. When the vesicles are brought
      into contact with a network of immobilized microtubules, membrane tubes and
      tubular networks are formed. Through systematic variation of the kinesin
      concentration and membrane composition we study the mechanism involved. We show
      that a threshold concentration of motor proteins is needed and that a low
      membrane tension facilitates tube formation. Forces involved in tube formation
      were measured directly with optical tweezers and are shown to depend only on the
      tension and bending rigidity of the membrane. The forces were found to be higher
      than can be generated by individual motor proteins, indicating that multiple
      motors were working together to pull tubes. We propose a simple mechanism by
      which individual motor proteins can dynamically associate into clusters that
      provide the force needed for the formation of tubes, explaining why, in contrast
      to earlier findings [Roux, A., Cappello, G., Cartaud, J., Prost, J., Goud, B. &
      Bassereau, P. (2002) Proc. Natl. Acad. Sci. USA 99, 5394-5399], motor proteins do
      not need to be physically linked to each other to be able to pull tubes.

PMID- 14663144
TI  - Molecular basis of calcium regulation in connexin-32 hemichannels.
AB  - In addition to forming gap-junction channels, a subset of connexins (Cxs) also
      form functional hemichannels. Most hemichannels are activated by depolarization,
      and opening depends critically on the external Ca2+ concentration. Here we
      describe the mechanisms of action and the structural determinants underlying the
      Ca2+ regulation of Cx32 hemichannels. At millimolar calcium concentrations,
      hemichannel voltage gating to the full open state of approximately 90 pS is
      inhibited, and ion conduction at negative voltages of the partially open
      hemichannels ( approximately 18 pS) is blocked. Thus, divalent cation blockage
      should be considered as a physiological mechanism to protect the cell from the
      potentially adverse effects of leaky hemichannels. A ring of 12 Asp residues
      within the external vestibule of the pore is responsible for the binding of Ca2+
      that accounts for both pore occlusion and blockage of gating. The residue Asp-169
      of one subunit and the Asp-178 of an adjacent subunit must be arranged precisely
      to allow interactions with Ca2+ to occur. Interestingly, a naturally occurring
      mutation (D178Y) that causes an inherited peripheral neuropathy induces a
      complete Ca2+ deregulation of Cx32 hemichannel activity, suggesting that this
      dysfunction may be involved in the pathogenesis of the neuropathy.

PMID- 14663145
TI  - Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of
      the mce1 operon.
AB  - An estimated one-third of the world's population is latently infected with
      Mycobacterium tuberculosis, the etiologic agent of tuberculosis. Here, we
      demonstrate that, unlike wild-type M. tuberculosis, a strain of M. tuberculosis
      disrupted in the mce1 operon was unable to enter a stable persistent state of
      infection in mouse lungs. Instead, the mutant continued to replicate and killed
      the mice more rapidly than did the wild-type strain. Histological examination of
      mouse lungs infected with the mutant strain revealed diffusely organized
      granulomas with aberrant inflammatory cell migration. Murine macrophages infected
      ex vivo with the mutant strain were reduced in their ability to produce tumor
      necrosis factor alpha, IL-6, monocyte chemoattractant protein 1, and nitric oxide
      (NO), but not IL-4. The mce1 mutant strain complemented with the mce1 genes
      stimulated tumor necrosis factor alpha and NO production by murine macrophages at
      levels stimulated by the wild-type strain. These observations indicate that the
      mce1 operon mutant is unable to stimulate T helper 1-type immunity in mice. The
      hypervirulence of the mutant strain may have resulted from its inability to
      stimulate a proinflammatory response that would otherwise induce organized
      granuloma formation and control the infection without killing the organism. The
      mce1 operon of M. tuberculosis may be involved in modulating the host
      inflammatory response in such a way that the bacterium can enter a persistent
      state without being eliminated or causing disease in the host.

PMID- 14663146
TI  - Climatic suitability for malaria transmission in Africa, 1911-1995.
AB  - Time series analysis of a climate-driven model of malaria transmission shows
      limited evidence for an increase in suitability during the last century across
      Africa. Outside areas where climate was always or never suitable, <17% of the
      continent showed significant trends in malaria transmission. Of these areas, 5.7%
      showed positive deterministic trends, 6.1% had negative deterministic trends, and
      5.1% exhibited stochastic trends. In areas with positive trends, precipitation,
      rather than temperature, was the primary forcing variable. This analysis
      highlights the need to examine the relationship between climate and malaria more
      closely and to fully consider nonclimatic factors as drivers of increased malaria
      transmission across the continent.

PMID- 14663147
TI  - Trans-editing of mischarged tRNAs.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are multidomain proteins that specifically
      attach amino acids to their cognate tRNAs. Their most conserved, and presumably
      evolutionarily oldest, domains are the catalytic cores, which activate amino
      acids and transfer them to the 3' ends of tRNAs. Additional domains appended to
      or inserted in the body of aaRSs increase efficiency and specificity of the
      aminoacylation process, either by providing additional tRNA contacts, or by
      hydrolyzing noncognate amino acid products (cis-editing). Here, we report
      specific tRNA-dependent trans-editing by aaRS-like proteins that reciprocate the
      editing domains of aaRSs, but not the remainder of the corresponding enzyme. A
      freestanding homologue of the prolyl-tRNA synthetase-editing domain, the PrdX
      protein from Clostridium sticklandii, efficiently and specifically hydrolyzes Ala
      tRNAPro. Similarly, autonomous alanyl-tRNA synthetase-editing domain homologues
      (AlaX proteins) from Methanosarcina barkeri and Sulfolobus solfataricus hydrolyze
      Ser-tRNAAla and Gly-tRNAAla substrates. The discovery of autonomous editing
      proteins efficient in hydrolyzing misacylated products provides a direct link
      between ancestral aaRSs consisting solely of the catalytic core and extant
      enzymes to which functionally independent modules are appended.

PMID- 14663148
TI  - Direct and distinguishable inhibitory roles for SUMO isoforms in the control of
      transcriptional synergy.
AB  - Functional interactions between factors bound at multiple sites on DNA often lead
      to a synergistic or more-than-additive transcriptional response. We previously
      defined a class of peptide sequences termed synergy control motifs (SC motifs)
      that function in multiple regulators by selectively inhibiting synergistic
      activity driven from multiple but not single response elements. By studying the
      prototypic SC motifs of the glucocorticoid receptor, we show that SC motifs
      inhibit transcription per se both in cis and in trans, and that a requirement for
      multiple contacts with DNA renders them selective for compound response elements.
      Notably, SC motifs are sites for SUMOylation, and the degree of modification
      correlates strongly with the extent of synergy control. Recruiting SUMO to the
      promoter either independently or as a fusion to the glucocorticoid receptor is
      sufficient to recapitulate the in trans and in cis inhibition by SC motifs
      without apparent changes in subcellular localization. Moreover, we find that the
      core ubiquitin fold domain of SUMO is sufficient for inhibition and that,
      independently of their potential for polySUMO chain formation, SUMO-2 and SUMO-3
      are more effective inhibitors than SUMO-1.

PMID- 14663149
TI  - Cap analysis gene expression for high-throughput analysis of transcriptional
      starting point and identification of promoter usage.
AB  - We introduce cap analysis gene expression (CAGE), which is based on preparation
      and sequencing of concatamers of DNA tags deriving from the initial 20
      nucleotides from 5' end mRNAs. CAGE allows high-throughout gene expression
      analysis and the profiling of transcriptional start points (TSP), including
      promoter usage analysis. By analyzing four libraries (brain, cortex, hippocampus,
      and cerebellum), we redefined more accurately the TSPs of 11-27% of the analyzed
      transcriptional units that were hit. The frequency of CAGE tags correlates well
      with results from other analyses, such as serial analysis of gene expression, and
      furthermore maps the TSPs more accurately, including in tissue-specific cases.
      The high-throughput nature of this technology paves the way for understanding
      gene networks via correlation of promoter usage and gene transcriptional factor
      expression.

PMID- 14663150
TI  - Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic
      glutamate receptor 3.
AB  - Cell surface receptor membrane localization is strongly dependent on protein
      protein interactions often involving regulation by
      phosphorylation/dephosphorylation of the intracellular domains of membrane
      proteins. The present study was carried out to identify metabotropic glutamate
      receptor (mGluR) 3 regulatory binding proteins. Using the yeast two-hybrid
      technique, we found that the 50-aa C-terminal cytoplasmic tail of mGluR3
      interacts specifically with protein phosphatase 2Calpha (PP2Calpha). This
      interaction was confirmed by GST pull-down and coimmunoprecipitation assays.
      mGluR3 interacts with PP2Calpha, beta, gamma, and delta isoforms; however, among
      the mGluR family only mGluR3 interacted with PP2C. The minimal interacting domain
      of mGluR3 comprised residues 836-855. Alignment between mGluR3 and mGluR2, a
      closely related group II receptor, indicated that this domain is not conserved
      between the two receptors. The mGluR3 cytoplasmic C-terminal tail contains one
      phosphorylation site for protein kinase A (Ser-845), but the phosphatase that
      dephosphorylates this site has not been previously identified. We find that PP2C,
      but not PP1, PP2A, or PP2B, dephosphorylates the mGluR3 cytoplasmic tail in
      vitro. The dephosphorylated form of the mGluR3 cytoplasmic tail, but not the
      equivalent region of mGluR2, inhibited PP2C assayed by using [32P]casein as a
      substrate. However, phosphorylation of the mGluR3 cytoplasmic tail at Ser-845
      inhibits the interaction with PP2C. These results indicate distinct functions for
      mGluR2 and mGluR3 and suggest a dynamic regulation of mGluR3 by PP2C.

PMID- 14663151
TI  - Marker succession during the development of keratinocytes from cultured human
      embryonic stem cells.
AB  - Human embryonic stem cells injected into scid mice produce nodules containing
      differentiated somatic tissues. From the trypsinized cells of such a nodule, we
      have recovered keratinocytes that can be grown in cell culture. The method of
      recovery is sensitive enough to detect small numbers of keratinocytes formed in
      the nodule, but for purposes of analysis, it is preferable to study the
      development of the entire keratinocyte lineage in culture. The principle of our
      analysis is the successive appearance of markers, including transcription factors
      with considerable specificity for the keratinocyte (p63 and basonuclin) and
      differentiation markers characteristic of its final state (keratin 14 and
      involucrin). We have determined the order of marker succession during the time-
      and migration-dependent development of keratinocytes from single embryoid bodies
      in cell culture. Of the markers we have examined, p63 was the earliest to appear
      in the keratinocyte lineage. The successive accumulation of later markers
      provides increasing certainty of emergence of the definitive keratinocyte.

PMID- 14663152
TI  - Markov chain Monte Carlo without likelihoods.
AB  - Many stochastic simulation approaches for generating observations from a
      posterior distribution depend on knowing a likelihood function. However, for many
      complex probability models, such likelihoods are either impossible or
      computationally prohibitive to obtain. Here we present a Markov chain Monte Carlo
      method for generating observations from a posterior distribution without the use
      of likelihoods. It can also be used in frequentist applications, in particular
      for maximum-likelihood estimation. The approach is illustrated by an example of
      ancestral inference in population genetics. A number of open problems are
      highlighted in the discussion.

PMID- 14663153
TI  - High frequency oscillatory ventilation suppresses inflammatory response in lung
      tissue and microdissected alveolar macrophages in surfactant depleted piglets.
AB  - The impact of high frequency oscillatory ventilation (HFOV) compared with
      intermittent mandatory ventilation (IMV) on oxygenation and pulmonary
      inflammatory response was studied in a surfactant depleted piglet model. After
      establishment of lung injury by bronchoalveolar lavage, piglets either received
      HFOV (n =5) or IMV (control; n = 5) for eight hours. PaO(2) was higher and mean
      pulmonary arterial pressure (MPAP) was lower with HFOV (HFOV versus control, mean
      +/- SEM; endpoint PaO(2): 252 +/- 73 versus 68 +/- 8.4 mm Hg; p < 0.001; MPAP: 22
      +/- 2.3 versus 34 +/- 2.5 mm Hg; p < 0.01). mRNA expression of interleukin (IL)-1
      beta, IL-6, IL-8, IL-10, TGF-beta 1, Endothelin-1, and adhesion molecules (E
      selectin, P-selectin, ICAM-1) in lung tissue was quantified by real time PCR
      normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase
      (HPRT). mRNA expression of all cytokines and adhesion molecules/HPRT was higher
      in controls (e.g.: HFOV versus control, mean +/- SEM; IL-1 beta/HPRT: 1.6 +/- 0.3
      versus 23.1 +/- 8.6 relative units (RU), p < 0.001; IL-8/HPRT: 8.5 +/- 2.0 versus
      63.5 +/- 15.2 RU, p < 0.001). IL-8/HPRT gene expression was quantified in
      microdissected single cells. With HFOV, IL-8 gene expression was highly reduced
      in alveolar macrophages: 10 +/- 3.4 copies IL-8 mRNA/copy HPRT mRNA versus 356 +/
      142; p < 0.05 (bronchiolar epithelial cells: 33 +/- 16 versus 208 +/- 108;
      alveolar septum: 2.1 +/- 1.3 versus 26 +/- 11; bronchiolar smooth muscle cells:
      1.3 +/- 0.3 versus 2.8 +/- 1.0; vascular smooth muscle cells: 0.7 +/- 0.3 versus
      1.1 +/- 0.4). In conclusion, HFOV improved oxygenation, reduced pulmonary
      arterial pressure and attenuated pulmonary inflammatory response.

PMID- 14663154
TI  - Cellular response to renal hypoxia is different in adolescent and infant rats.
AB  - Immature renal tubules are more tolerant to ischemia than mature renal tubules.
      Here we compared the developmental pattern for some cellular responses evoked by
      hypoxia and reoxygenation in renal proximal tubules from 10- and 40-day-old rats.
      Redistribution of Na(+)-K(+)-ATPase from the plasma membrane was studied by
      confocal microscopy techniques in primary cultured renal proximal tubular cells.
      The developmental expression of Na(+)-K(+)-ATPase, micro-calpain and heme
      oxygenase-1 was measured by RT-PCR techniques in rat renal cortex. In response to
      hypoxia Na(+)-K(+)-ATPase redistribution from the plasma membrane was almost 2
      fold increased in cells isolated from mature kidneys compared with cells isolated
      from immature kidneys. Reoxygenation resulted in a complete reestablishment of
      Na(+)-K(+)-ATPase in the plasma membrane in the immature but not in the mature
      cells. The dissociation of Na(+)-K(+)-ATPase from the plasma membrane was
      associated with a reduced activity and a reduced expression of Na(+)-K(+)-ATPase
      in the mature but not in the immature tubular cells. The expression of micro
      calpain, a factor shown to induce ischemic injury to proximal tubular cells, was
      significantly lower in the immature compared with the mature kidney, whereas the
      expression of heme oxygenase-1, a factor shown to protect from renal ischemic
      injury, was significantly higher in the immature kidney. The results help to
      explain the increased tolerance of the immature kidney to injury caused by
      ischemia and reperfusion.

PMID- 14663155
TI  - Structure-function relationships in enzymatically modified articular cartilage.
AB  - The present study is aimed at revealing structure-function relationships of
      bovine patellar articular cartilage. Collagenase, chondroitinase ABC and elastase
      were used for controlled and selective enzymatic modifications of cartilage
      structure, composition and functional properties. The effects of the enzymatic
      degradations were quantitatively evaluated using quantitative polarized light
      microscopy, digital densitometry of safranin O-stained sections as well as with
      biochemical and biomechanical techniques. The parameters related to tissue
      composition and structure were correlated with the indentation stiffness of
      cartilage. In general, tissue alterations after enzymatic digestions were
      restricted to the superficial cartilage. All enzymatic degradations induced
      superficial proteoglycan (PG) depletion. Collagenase also induced detectable
      superficial collagen damage, though without causing cartilage fibrillation or
      tissue swelling. Quantitative microscopic techniques were more sensitive than
      biochemical methods in detecting these changes. The Young's modulus of cartilage
      decreased after enzymatic treatments indicating significant softening of the
      tissue. The PG concentration of the superficial zone proved to be the major
      determinant of the Young's modulus (r(2) = 0.767, n = 72, p < 0.001). Results of
      the present study indicate that specific enzymatic degradations of the tissue PGs
      and collagen can provide reproducible experimental models to clarify the
      structure-function relationships of cartilage. Effects of these models mimic the
      changes observed in early osteoarthrosis. Biomechanical testing and quantitative
      microscopic techniques proved to be powerful tools for detecting the superficial
      structural and compositional changes while the biochemical measurements on the
      whole uncalcified cartilage were less sensitive.

PMID- 14663156
TI  - Deformation of chondrocytes in articular cartilage under compressive load: a
      morphological study.
AB  - The main function of articular cartilage is to transmit load. The objective of
      this study was to describe the deformation of chondrocytes under static loading
      and its relation to collagen matrix deformation. Whole intact rabbit knee joints
      were loaded statically with either high or low magnitude and long or short
      duration. Specimens were cryopreserved while under load and prepared for
      morphological evaluation by field emission scanning electron microscopy. With
      this method an immediate preservation of the chondrocyte in its loaded state was
      possible. Static compression of articular cartilage produced a zone-specific
      deformation of chondrocyte shape, depending on the magnitude and duration of
      load. Under high-force and long-duration loading, the chondrocytes showed
      considerable deformation concomitant with the highly deformed collagen fibres.
      Chondrocyte deformation occurred mostly in the transitional and upper radial
      zones and less in the lower layers. There was no significant change of the
      chondrocyte shape in the tangential zone under high- or low-force short-duration
      loading. These results show that the chondrocytes undergo significant changes in
      shape ex vivo and that they are sensitive to differences in the magnitude and
      duration of loads being applied. Chondrocyte deformation is strongly linked to
      the deformation of the surrounding cartilage collagen matrix.

PMID- 14663157
TI  - Mechanical conditioning influences the metabolic response of cell-seeded
      constructs.
AB  - Injuries and degenerative diseases to load-bearing soft tissues are extremely
      common in hospital clinics and involve all ages of the population. Tissue
      engineering provides a major focus for developments within this area due to the
      relative failure of graft and prosthetic-based strategies. On implantation, such
      systems will be subjected to normal physiological forces. It is important,
      therefore, to understand the effects of mechanical conditioning of cells within
      repair systems to predict their response and ultimate success in vivo. In the
      current study two well-characterised model systems, involving dermal fibroblasts
      seeded onto silicone membranes and chondrocytes seeded in agarose constructs,
      have been used to study the effects of mechanical loading on cellular activity.
      The data presented demonstrate that both the tensile conditioning of fibroblasts
      in monolayer and the compressive loading of chondrocytes in three-dimensional
      agarose constructs produced distinct responses. In particular, the nature of the
      strain field associated with the tensile system is important in determining the
      ultimate cell response. Equally within the compressive system the influence of
      dynamic frequency was shown to be important. The other critical factors in
      determining response to both types of conditioning are associated with the age of
      the cell and its original location within the tissue.

PMID- 14663158
TI  - Distribution and localization of vinculin-talin-integrin system and dystrophin
      glycoprotein complex in human skeletal muscle. Immunohistochemical study using
      confocal laser scanning microscopy.
AB  - The vinculin-talin-integrin system and the dystrophin-glycoprotein complex (DGC)
      are two protein systems with structural and signaling functions, allowing
      interaction between muscle fibers and extracellular matrix. Although numerous
      studies have been conducted on these systems, their localization and distribution
      patterns along the nonjunctional sarcolemma are not clear. On this basis, we
      carried out an indirect immunofluorescence study on the vastus lateralis muscle
      of human adults not affected by neuromuscular diseases to better define these
      patterns. Our results showed that all tested proteins of the two systems have a
      costameric distribution; all tested proteins of the two systems colocalize with
      each other (about 90-95% of the cases); only alpha-sarcoglycan in a few cases
      (about 6%) does not colocalize with other proteins; in about 9-10% of the cases,
      dystrophin and beta-dystroglycan colocalize partially with other proteins; all
      tested proteins can be localized in different fibers, both in the region of the
      sarcolemma over I or A bands. The colocalization between the vinculin-talin
      integrin and DGC systems may imply their functional interaction involving the
      structural aspect, by providing a stronger adhesion between sarcolemma and
      extracellular matrix in well-defined regions of the muscle fiber. Besides, their
      colocalization may suggest the existence of a mechanism of mutual modulation of
      the transmitted signals. This reciprocal control may determine, in different
      conditions, the prevalence of one system over another with a consequent
      transmission of different messages to the sarcolemma-associated cytoskeleton.

PMID- 14663159
TI  - The mesencephalic trigeminal nucleus of the duck: development and apoptosis.
AB  - The normal development of the mesencephalic trigeminal nucleus (MesV) of the
      white Peking duck (Anas platyrhynchos) was studied from the 9th day of incubation
      until hatching and during adulthood. In the early days of embryonic development,
      neurons are present in the posterior commissure and in the mesenchymal tissue
      outside the leptomeninges in addition to those in the tectal commissure (TC) and
      in the optic tectum. Following the internucleosomal cleavage of DNA, a massive
      loss of neurons in the MesV starts in the 11-day embryo and continues until the
      15th day of incubation. On the 16th day, the nucleus consists of a numerically
      larger medial division located in the TC and a smaller lateral division within
      the stratum griseum periventriculare as is found in the adult animal. The
      programmed cell death occurring in the MesV is discussed herein and correlated
      with the analogous apoptotic phenomena observed in the trigeminal motor nucleus.

PMID- 14663160
TI  - High-dose therapy and autologous stem cell transplantation in relapsed and
      refractory Hodgkin's disease: outcome based on a prognostic model.
AB  - We evaluated the results of high-dose therapy (HDT) and autologous hematopoietic
      stem cell transplantation (ASCT) in patients with relapsed or primary refractory
      Hodgkin's disease (HD), using a previously reported prognostic model based on the
      presence of three poor prognostic factors at the start of salvage
      therapy/preparative regimen: B symptoms, extranodal disease and the duration of
      last complete response of less than 1 year. Based on this model, the patients
      were divided into low-risk and high-risk groups. Between 1993 and 2001, 24
      patients with HD were treated with HDT and ASCT. Eighteen of the 24 patients had
      0-1 risk factors (low-risk group) and 6 patients had 2-3 risk factors (high-risk
      group). Using Kaplan-Meier analysis, after a median follow-up of 40.5 months, the
      progression-free survival (PFS) was 48%, and the overall survival (OS) was 55%.
      PFS in the low-risk group was 56%, and in the high-risk group 17% (p < 0.001). OS
      in the low-risk group was 68% and in the high-risk group it was 18% (p < 0.001).
      The 100-day transplant-related mortality for the entire group was 16%. Our
      results are comparable to those reported in previous clinical trials for patients
      with refractory and relapsed HD treated with HDT and ASCT. The use of a
      prognostic model appears useful for predicting the outcome of HDT and ASCT for HD
      patients, and may play an important role in choosing the appropriate therapy for
      these patients.

PMID- 14663161
TI  - Results of an autologous noncryopreserved, unmanipulated peripheral blood
      hematopoietic stem cell transplant program: a single-institution, 10-year
      experience.
AB  - BACKGROUND: Methods to simplify the stem cell transplantation procedures are
      needed mainly in developing countries. We have previously shown that unprocessed
      leukapheresis material is useful to restore hematopoiesis after high-dose
      chemotherapy. METHODS: Over a 10-year period in a private practice setting, we
      prospectively performed autotransplants using noncryopreserved and unmanipulated
      peripheral blood stem cells mobilized from the bone marrow to the peripheral
      blood by means of filgrastim and using a single-day conditioning regimen with
      high dose (200 mg/m2) melphalan. RESULTS: Forty-six individuals were given 50
      autografts. The median age of the patients was 33 years (range 8-69). Twenty-two
      patients with acute leukemia (13 with myeloblastic and 9 with lymphoblastic
      leukemia), 4 with chronic myelogenous leukemia, 6 with multiple myeloma, 7 with
      Hodgkin's disease, 3 with non-Hodgkin's lymphoma and 4 with metastatic breast
      carcinoma were included. The median time to achieve >0.5 x 10(9)/l granulocytes
      was 14 days (range 0-86), whereas the median time to achieve >20 x 10(9)/l
      platelets was 25 days (range 0-102). The 3,300-day posttransplant survival was
      63%, the median posttransplant overall survival was over 3,300 days, the 3,300
      day disease-free survival was 50% and the transplant-related mortality was 2%.
      The procedure was performed entirely on an outpatient basis in the case of 48
      autografts (96%). The approximate cost of each graft was 7,500 USD. CONCLUSION:
      This simplified method to autograft patients, avoiding in-hospital stays, purging
      procedures and cryopreservation of the cells, is feasible and results in a
      substantial decrease in the cost of the autologous hematopoietic stem cell
      transplantation methods.

PMID- 14663162
TI  - Long-term results of the immunosuppressive treatment of patients with severe
      acquired aplastic anemia: a single institution study.
AB  - In Mexico, only few patients can afford adequate treatment for aplastic anemia.
      In a single institution 61 individuals with severe aplastic anemia (SAA) were
      identified; of these, 33 were followed for at least 3 months, 26 could be treated
      with immunosuppression (IS), 20 with antithymocyte globulin and cyclosporin A
      (ATG + CyA) and 6 with CyA, whereas 7 individuals were given only anabolic
      androgens. In the patients treated with IS a complete remission was achieved in
      12 and a partial remission in 6, the overall response rate being 69%. The 5,729
      day overall survival (SV) was 54%; it was superior for the patients who received
      both ATG and CyA (58 vs. 50%). These data contrast with those of the patients who
      were given only androgens: 14% SV at 5,510 days. Within the group of patients who
      received IS, one developed acute myelogenous leukemia, another paroxysmal
      nocturnal hemoglobinuria and another a primary Sjogren's syndrome-associated low
      grade, B cell, non-Hodgkin's lymphoma. Two individuals who received IS were
      allografted from HLA-identical siblings and survived 70 and 413 days after the
      allograft. On the other hand, we also found that, for several reasons, mainly
      economic ones, only 41% of individuals with SAA finally benefited from the best
      immunosuppressive therapeutic approach. IS was a good therapeutic choice for some
      patients with SAA, clearly better than androgen treatment.

PMID- 14663163
TI  - Granulocytic sarcoma of the pancreas. A report of one case and review of the
      literature.
AB  - Granulocytic sarcoma is an extramedullary collection of myeloblasts. Granulocytic
      sarcomas usually arise during the course of acute myeloid leukemia, although they
      also occur infrequently in chronic myeloid leukemia and other myeloproliferative
      disorders. We are reporting a very unusual presentation of granulocytic sarcoma
      in a patient with poorly differentiated (FAB type M2) acute myeloid leukemia. The
      patient was in complete remission from leukemia when he presented obstructive
      jaundice due to a pancreatic mass consisting of myeloblasts. A literature search
      identified only five previously reported cases of granulocytic sarcoma of the
      pancreas. Those cases are also reviewed here with emphasis on their clinical
      characteristics, diagnostic approaches, and management of this interesting and
      challenging entity.

PMID- 14663164
TI  - Splenectomy for massive splenic infarction unmasks paroxysmal nocturnal
      hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder characterized by
      pancytopenia, hemolysis, and thrombosis. Abdominal vein thrombosis is a life
      threatening manifestation of this disease. We present a patient with complete
      spleen necrosis due to thrombosis of the splenic vessels. After splenectomy,
      other causes of thrombophilia were excluded and the diagnosis of PNH was
      established. The patient was put on anticoagulation but despite the prophylactic
      international normalized ratio maintained over the last 18 months of follow-up,
      he had another episode of intrahepatic thrombosis which was treated with tissue
      plasminogen activator thrombolysis.

PMID- 14663165
TI  - Spontaneous adrenal haemorrhage as a manifestation of isolated relapse of non
      Hodgkin's lymphoma.
AB  - Retroperitoneal haemorrhage due to metastatic disease is a rare event not
      previously reported in lymphomas. We describe a 36-year-old woman diagnosed with
      diffuse large B cell lymphoma (DLBCL) of bone marrow, liver and spleen presenting
      in the leukaemic phase. The patient attained complete remission after 'ALL-like'
      chemotherapy (cyclophosphamide, vincristine, adriamycin, dexamethasone); 22
      months later, she developed an isolated central nervous system (CNS) relapse
      which was successfully managed with a combination of chemotherapy and CNS
      irradiation. Six months later, she was rehospitalized because of abdominal pain;
      an MRI revealed a large haemorrhagic mass in the left adrenal. Surgical removal
      of the lesion confirmed an adrenal relapse of the primary DLBCL.

PMID- 14663166
TI  - Excretion of granulocyte colony-stimulating factor into human breast milk.

PMID- 14663167
TI  - Vascular endothelial growth factor and thrombopoietin in patients with essential
      thrombocythemia and polycythemia vera and thrombotic complications.

PMID- 14663168
TI  - Cytokines and erythropoietin in the blood of patients with erythroblastemia.

PMID- 14663169
TI  - Pharmacogenetics of gemtuzumab-associated hepatic sinusoidal occlusion syndrome
      after hematopoietic stem cell transplant.

PMID- 14663170
TI  - Acute intravascular hemolysis due to ABO-incompatible platelet transfusion.

PMID- 14663171
TI  - Serum transferrin receptor concentrations correlate more strongly with red cell
      indices than with iron parameters in iron-deficient adolescents.

PMID- 14663172
TI  - Fatal hemophagocytic lymphohistiocytosis with clonal and granular T cell
      proliferation in an infant.

PMID- 14663173
TI  - Search for factor V Arg306 Cambridge and Hong Kong mutations in mixed Hungarian
      population samples.

PMID- 14663174
TI  - Sickle cell trait associated with hereditary spherocytosis: a potentially life
      threatening coexistence.

PMID- 14663175
TI  - Immune status of thalassemic patients receiving deferiprone or combined
      deferiprone and desferrioxamine chelation treatment.

PMID- 14663177
TI  - Unique qualities define successful healthcare leaders.
AB  - The complexity, structure, pace of change and distribution of authority in
      healthcare institutions make them radically different in terms of leadership
      required than businesses, the military or the government. With multiple internal
      and external stakeholders, the perception of leadership may be as important as
      its actual quality, making it much more difficult to define, evaluate and
      replicate in healthcare.

PMID- 14663178
TI  - The effect of musicianship on pitch memory in performance matched groups.
AB  - We compared brain activation patterns between musicians and non-musicians
      (matched in performance score) while they performed a pitch memory task (using a
      sparse temporal sampling fMRI method). Both groups showed bilateral activation of
      the superior temporal, supramarginal, posterior middle and inferior frontal
      gyrus, and superior parietal lobe. Musicians showed more right temporal and
      supramarginal gyrus activation while non-musicians had more right primary and
      left secondary auditory cortex activation. Since both groups' performance were
      matched, these results probably indicate processing differences between groups
      that are possibly related to musical training. Non-musicians rely more on brain
      regions important for pitch discrimination while musicians prefer to use brain
      regions specialized in short-term memory and recall to perform well in this pitch
      memory task.

PMID- 14663179
TI  - Neural correlates of semantic effects on grasping familiar objects.
AB  - This study used event-related fMRI to explore the neural basis of semantic
      involvement when performing a visually guided grasping movement. Three types of
      object images were presented in random order: familiar objects with handles (FH+)
      familiar objects without handles (FH-) and geometrical objects with a handle-like
      part (GH+). Subjects were then instructed to configure an appropriate hand shape
      for grasping the object. Common activations were found for all event types when
      contrasted with baseline. Activation of the anterior part of the rostral
      cingulate motor area was detected for only the FH+ condition and these results
      imply that the appropriate selection of multiple motor schemata took place in
      this region.

PMID- 14663180
TI  - Cortical processing of musical consonance: an evoked potential study.
AB  - Cortical processes underlying perception of musical consonance were investigated
      by long-latency auditory evoked potentials (EPs). Subjects listened to a random
      sequence of dyadic pure tones paired at various pitch intervals (1, 4, 6, 7, or 9
      semitones). Amplitudes of P2 and N2 components of auditory EPs were significantly
      modulated by pitch interval of the dyads, being most negative for 1 semitone
      (minor second) and least negative or most positive for 7 semitones (perfect
      fifth). The results indicate that neural processing of consonance depend not only
      on peripheral mechanisms in the inner ear but also on higher associative
      processing of pitch relationships in the cerebral cortex.

PMID- 14663181
TI  - Familiar words capture the attention of 11-month-olds in less than 250 ms.
AB  - The capacity of human infants to discriminate contrasting speech sounds
      specializes to the native language by the end of the first year of life, when the
      first signs of word recognition have also been found, using behavioural measures.
      The extent of voluntary attentional involvement in such word recognition has not
      been explored, however, nor do we know what its neural time-course may be. Here
      we demonstrate that 11-month-old children shift their attention automatically to
      familiar words within 250 ms of presentation onset by measuring event-related
      potentials elicited by familiar and unfamiliar words. A significant modulation of
      the first negative peak (N200), known to index implicit change detection in
      adults, was induced by word familiarity in the infants.

PMID- 14663182
TI  - A beta 1-42 induces production of quinolinic acid by human macrophages and
      microglia.
AB  - We hypothesized that the tryptophan catabolites produced through the kynurenine
      pathway (KP), and more particularly the excitotoxin quinolinic acid (QUIN), may
      play an important role in the pathogenesis of Alzheimer's disease (AD). In this
      study, we demonstrated that aggregated amyloid peptide A beta 1-42 induced
      indoleamine 2,3-dioxygenase (IDO) expression and resulted in a significant
      increase in production of QUIN by human primary macrophages and microglia. In
      contrast, A beta 1-40 and prion peptide (PrP) 106-126 did not induce any
      significant increase in QUIN production. These data imply that local QUIN
      production may be one of the factors involved in the pathogenesis of neuronal
      damage in AD.

PMID- 14663183
TI  - Inverse amygdala and medial prefrontal cortex responses to surprised faces.
AB  - Here we show inverse fMRI activation patterns in amygdala and medial prefrontal
      cortex (mPFC) depending upon whether subjects interpreted surprised facial
      expressions positively or negatively. More negative interpretations of surprised
      faces were associated with greater signal changes in the right ventral amygdala,
      while more positive interpretations were associated with greater signal changes
      in the ventral mPFC. Accordingly, signal change within these two areas was
      inversely correlated. Thus, individual differences in the judgment of surprised
      faces are related to a systematic inverse relationship between amygdala and mPFC
      activity, a circuitry that the animal literature suggests is critical to the
      assessment of stimuli that predict potential positive vs negative outcomes.

PMID- 14663184
TI  - Word length modulates neural activity in auditory cortex during covert object
      naming.
AB  - Several lines of evidence show that posterior portions of left auditory cortex
      participate in aspects of speech production. A current hypothesis is that these
      regions play a specific role in processing phonological codes. We used event
      related fMRI to test this hypothesis. Subjects covertly named objects that had
      names varying in length from one to four syllables. Behavioral data, both in
      previous work and in the present study, show an increase in naming reaction time
      as words get longer, reflecting the increase in phonological load. If left
      posterior auditory areas participate in phonological aspects of production, word
      length should modulate neural activity in this region. Object naming activated
      the left planum temporale in each subject, confirming previous findings of
      auditory cortex involvement in speech production. The timecourse of activation in
      this region showed a length effect, consistent with its hypothesized role in
      phonological processing. Similar effects were also observed in premotor cortex,
      but not in occipital-temporal cortex, which presumably supports visual processing
      of the pictures to be named.

PMID- 14663185
TI  - Regulation of hippocampal parkin protein by corticosteroids.
AB  - Parkin is a protein that when mutated leads to an inherited form of Parkinson's
      disease. Under normal conditions, this molecule has multiple functions in
      different cell types, including protein degradation and tumor suppression. To
      understand the relationship between parkin and circulating corticosteroid
      hormones, we studied the long-term depletion of corticosterone due to bilateral
      adrenalectomy in rats. We show that adrenalectomy deletes the expected expression
      of nuclear parkin in hippocampal neurons. Notably, the effect of adrenalectomy on
      parkin was prevented by corticosterone hormone replacement therapy. This finding
      suggests that adrenal hormones may be critical in sustaining parkin
      ubiquitinating activity in the rat hippocampus.

PMID- 14663186
TI  - An aggregate-prone conformational epitope in trinucleotide repeat diseases.
AB  - A broad range of neurodegenerative disorders is associated with accumulation of
      misfolded protein that is toxic to the cells. Knowledge of the conformational
      structure of the protein implicated is essential for understanding how an
      aggregate-prone protein causes disease. Here we show that a conformational
      epitope associated with aggregation property and cell toxicity is preserved in
      homopolymeric amino acid stretches implicated in oculopharyngeal muscular
      dystrophy (OPMD) and polyglutamine diseases. These disorders are characterized by
      the nuclear inclusions and a genetic gain of function. This is the first report
      of a candidate pathogenic structure, which may trigger aggregation of the
      proteins in trinucleotide repeat diseases including OPMD and polyglutamine
      diseases. It provides a possible therapeutic target useful for these disorders.

PMID- 14663187
TI  - Responses of extrastriate cortex to switching perception of ambiguous visual
      motion stimuli.
AB  - We recently found that in bistable apparent motion (AM) both the motion complex
      (hMT/V5+) and kinetic occipital area (KO) transiently activated whenever
      perception switched in the spinning wheel illusion. Here, we tested the
      specificity of this result with another bistable AM stimulus, the dynamic dot
      quartet, that does not involve kinetic contours. We observed significant
      activations in hMT/V5+, but not in KO. This indicates that neural activity in
      functionally specialized extrastriate visual areas during switching perception of
      ambiguous input depends on stimulus features in a finely tuned way suitable to
      encode perceptual content in the absence of sensory input changes.

PMID- 14663188
TI  - GDNF and bFGF are differentially involved in glial cell differentiation and
      neurite bundle formation in cultures from chick embryonic ciliary ganglia.
AB  - We have shown that the neurotrophic factors glial cell line-derived neurotrophic
      factor (GDNF) and basic fibroblast growth factor (bFGF) exert different effects
      on glial cells in cultures from chick embryo ciliary ganglia. bFGF acts as a
      mitogen on glial cells, and induces their aggregation to neuronal bodies; after
      48 h of culture no glial cells could be observed along neurites. GDNF has no
      proliferative role; in contrast, it promotes the expression of the
      differentiative marker O4 and the association of glial cell bodies to neurites to
      form robust bundles.

PMID- 14663189
TI  - Increased viability of PC12 cells exposed to amyloid-beta peptide by transduction
      with human TAT-methionine sulfoxide reductase.
AB  - Methionine sulfoxide reductase (MsrA) catalyzes the reduction of methionine
      sulfoxide to methionine, which is able to scavenge oxidatively damaged proteins.
      Oxidative stress has been linked to the pathophysiology of Alzheimer's disease,
      and a decrease in MsrA activity has also been implicated in Alzheimer's disease.
      The transactivator of transcription (TAT) protein from human immunodeficiency
      virus 1 has been used to deliver full-length proteins into mammalian cells. We
      produced genetic in-frame TAT-MsrA fusion protein and successfully transduced it
      into PC12 cells, where it showed enzymatic activity. We showed that transduction
      of TAT-MsrA increased cell viability and reduced DNA fragmentation in PC12 cells
      treated with amyloid-beta (A beta). We suggest that MsrA transduction could
      reduce the oxidative damage caused to cellular proteins by A beta and could play
      a role in the treatment of Alzheimer's disease.

PMID- 14663190
TI  - Pallial origin of mitral cells in the olfactory bulbs of Xenopus.
AB  - We used two developmental transcription factors, x-Eomes (T-box family) and x
      Lhx5 (LIM-homeodomain family), to follow the origin and development of the
      olfactory bulbs in Xenopus. During embryonic and larval development, x-Eomes and
      x-Lhx5 were expressed in highly similar patterns, in the lateral and latero
      ventral wall of the pallium. In adults, both markers were strongly and
      specifically expressed in mitral cells, i.e., in the projection neurons of the
      main and accessory olfactory bulbs. These results demonstrate the pallial origin
      of the olfactory projecting cells in Xenopus. Combined with previous results
      suggesting a subpallial origin for olfactory interneurons, these findings
      emphasize the dual origin of different neuronal populations in the bulbs of
      anamniotes, and suggest that this organization is a shared feature of tetrapods.

PMID- 14663191
TI  - Effects of unilateral labyrinthectomy on GAD, GAT1 and GABA receptor gene
      expression in the rat vestibular nucleus.
AB  - To elucidate the role of the GABAergic neuronal system in the recovery from
      peripheral vestibular damage (unilateral labyrinthectomy), we used a real-time
      quantitative reverse transcription-polymerase chain reaction method to
      investigate the mRNA expression of GAD65, GAD67, the GABAA receptor alpha1
      subunit, the GABAB R1 subunit, and the GABA transporter GAT1, in the vestibular
      nucleus complex of the rat 6 and 50 h following the lesion GAD65 and GAD67 gene
      expression were also measured in the flocculus. The GABAA alpha 1 subunit mRNA
      was up-regulated in the ipsilateral vestibular nucleus 6 h post-lesion but
      decreased in expression thereafter. GAD65 mRNA was up-regulated in the vestibular
      nuclei bilaterally 50 h after the lesion. In the flocculus, GAD65 mRNA expression
      was bilaterally up-regulated 50 h post-operatively. GAT1 mRNA expression was
      initially up-regulated in the ipsilateral vestibular nucleus and then underwent a
      bilateral increase 50 h post-operatively. These results demonstrate that
      following unilateral labyrinthectomy, major changes in the expression of GAD, GAT
      and GABA receptor subunit genes occur in the vestibular nucleus, which are likely
      to affect the process of behavioural recovery.

PMID- 14663192
TI  - Gait-dependent integration of neck muscle afferent input.
AB  - We investigated the integration of neck muscle afferents during walking and
      running. Subjects walked or ran straight ahead, with or without an additional
      mass (20% of body weight). They performed all trials without vibration and with
      continuous vibration (80 Hz) applied to the lateral aspect of the neck. Vibration
      systematically caused body deviation toward the side opposite to the stimulation.
      The amplitude of vibration-induced body deviations was dramatically larger for
      walking (21.6 +/- 4.6 degrees ) than for running (8.0 +/- 2.5 degrees ). The
      additional mass marginally straightened body trajectory (average 5.6%),
      indicating that the gait-dependent effect of neck vibration cannot solely be
      attributed to differences in body inertia between walking and running. We
      concluded that neck muscle afferences are selectively gated according to the gait
      performed.

PMID- 14663193
TI  - 2-Deoxy-D-glucose protects retinal ganglion cells against excitotoxicity.
AB  - Caloric restriction mimicked by administration of 2-deoxy-D-glucose (2DG) has
      been shown to protect cerebral neurons against ischemia and excitotoxicity. This
      study examined the protective effects of pretreatment with 2DG on retinal neurons
      in N-methyl-D-aspartate (NMDA) excitotoxicity in rats. There was a significantly
      reduced number of TUNEL-labeled cells in the retinal ganglion cell layer 18 h
      after intravitreal injection of NMDA with 2DG pretreatment. At 7 days after NMDA,
      2DG pretreatment significantly preserved neurons in the retinal ganglion cell
      layer and reduced immunoreactivity of glial fibrillary acidic proteins in
      retinas. Our findings demonstrate that caloric restriction mimicked by 2DG
      protects retinas from NMDA excitotoxicity.

PMID- 14663194
TI  - Expression of proteinase-activated receptors in mouse microglial cells.
AB  - Microglia are the resident immune cells of the CNS: they are activated rapidly by
      CNS damage and perform the function of tissue macrophages. The first steps during
      microglial activation are currently under intense study, and it is widely
      believed that substances released from damaged brain tissue can trigger this
      process. We recently reported that the blood coagulation factor thrombin, which
      enters the CNS during breakdown of the blood-brain barrier, activates microglial
      cells. The cellular effects of thrombin and trypsin-like proteases are mediated
      by proteinase-activated receptors (PARs). Based on our prior data we hypothesized
      that microglial cells express these receptors. Using RT-PCR and flow cytometry,
      we report that primary mouse microglial cells, as well as the murine microglial
      cell lines BV-2 and N9, indeed express PARs, albeit at different levels.
      Demonstrating multiple PARs on microglia may enhance the attractiveness of PARs
      as therapeutic targets in neuroinflammatory disorders.

PMID- 14663195
TI  - Increased aquaporin-4 expression in ammonia-treated cultured astrocytes.
AB  - Brain edema is a serious complication of hepatic encephalopathy associated with
      fulminant hepatic failure (FHF). Factors responsible for such swelling are not
      clear, but ammonia, a toxin strongly implicated in FHF, is known to induce
      astrocyte swelling. The mechanism(s) responsible for ammonia-induced swelling,
      however, are not known. Aquaporins are plasma membrane proteins that mediate
      transmembrane water movement. To investigate the potential role of aquaporins in
      astrocyte swelling, we measured aquaporin-4 (AQP-4) protein expression in
      cultured astrocytes exposed to 5 mM NH4Cl. AQP-4 levels significantly increased
      10 h after treatment with ammonia, and displayed a progressive rise up to 48 h,
      which appeared to precede the onset of astrocyte swelling. AQP-4 may be involved
      in the astrocyte swelling associated with hyperammonemic states.

PMID- 14663196
TI  - Orphanin FQ/nociceptin blocks methamphetamine place preference in rats.
AB  - Orphanin FQ/nociceptin (NOC) has been reported to regulate dopaminergic
      neurotransmission in rewarding pathway, and to suppress the development of
      conditioned place preference (CPP) induced by certain addictive drugs. In this
      study, we investigated the effect of NOC on CPP induced by repeated
      administration of methamphetamine (MAP) in rats. Repeated administration of MAP
      (1 mg/kg, i.p.) induced substantial CPP. MAP-induced CPP was completely
      suppressed by NOC (10 nmol, i.c.v.). Pretreatment with [Nphe1]nociceptin(1-13)NH2
      (50 nmol, i.c.v.), an antagonist of the NOC receptor, antagonized the suppressive
      effect of NOC on MAP-induced CPP. These results suggest that NOC blocks MAP
      induced CPP by activation of the NOC receptor.

PMID- 14663197
TI  - Hypotensive effects of neuromedin U microinjected into the cardiovascular-related
      region of the rat nucleus tractus solitarius.
AB  - Neuromedin U (NMU) is a brain-gut peptide with potent contractile effects on the
      uterus and smooth muscle. Intracerebroventricular injection of NMU reportedly
      decreased food intake and body-weight gain in the rat. We evaluated the effects
      of NMU delivered by microinjection into the rat nucleus tractus solitarius (NTS)
      on cardiovascular responses. At the concentrations used (5, 10 or 50 pmol), the
      intra-NTS injection of NMU in artificial cerebrospinal fluid produced a
      significant reduction in both the mean arterial pressure and heart rate. The
      hypotensive responses were dose dependent. Our findings suggest that NMU may act
      as a neurotransmitter or neuromodulative substance that causes excitation of
      neurons in the NTS and that it may play a role in cardiovascular regulation in
      vivo.

PMID- 14663198
TI  - Loss of cell adhesion impairs the early response of TrkA to nerve growth factor
      (NGF).
AB  - Within the in vitro model of nerve growth factor (NGF)-dependent differentiation
      of PC12 cells, loss of adhesion is known to interfere with certain neurotrophic
      responses and not with others. The present analysis of early NGF signaling shows
      that the upstream activation of TrkA, as well as the recruitment of the adaptor
      protein Shc, are dramatically attenuated upon loss of cell adhesion, while the
      downstream activation of ERK1/2 is unaffected. That loss of cell adhesion
      interferes with the primary signaling response to NGF (i.e. autophosphorylation
      of TrkA) may explain why suspended PC12 cells fail to morphologically
      differentiate in response to NGF. The possibility that established adhesion
      driven mechanisms underlie the full responsiveness of TrkA to NGF is discussed.

PMID- 14663199
TI  - Herbimycin A induces sympathetic neuron survival and protects against hypoxia.
AB  - We have examined how herbimycin affects the survival and neuritogenesis of avian
      sympathetic neurons. Herbimycin promoted sympathetic neuron survival and
      neuritogenesis. At higher concentrations (> or = 100 ng/ml), herbimycin still
      enhanced neuron survival but blocked neuritogenesis. Addition of herbimycin (10
      30 ng/ml) to neurons cultured in the presence of NGF or retinal conditioned
      medium altered neuronal morphology, with an increase in the number of neurites.
      Addition of NGF during hypoxia rescued 52% of the neurons compared to 14%
      survival in control conditions. Herbimycin alone rescued about 50% of the
      neurons. In the presence of NGF and 100 ng/ml herbimycin, 81% of the neurons
      survived hypoxia. Our results show that herbimycin promotes survival of chick
      sympathetic neurons and potentiates the effects of NGF.

PMID- 14663200
TI  - Modulation of the JNK and p38 pathways by cdk5 protein kinase in a transgenic
      mouse model of Alzheimer's disease.
AB  - In this study we have used the transgenic mouse model Tg2576 to analyze the
      involvement of anomalous loss of regulation of cdk5 and the stress kinases JNK
      and p38 in brain neuronal death as related to neurodegenerative disorders such as
      Alzheimer's disease. Previous studies on hippocampal cells led us to the
      discovery that the cdk5/p35 complex is activated in neurodegeneration, a finding
      that was confirmed later in the transgenic mouse model. Here we show a link
      between the cdk5 system and JNK and p38 phosphoproteins, as an alternative
      pathway to neuronal death. Brains of the Tg2576 transgenic mice overexpressing
      amyloid precursor protein exhibited immunoreactivity with the phosphoproteins p
      JNK, p-p38 and the GTPase protein Rac1 surrounding neuritic plaques. A
      significant increase in the immunodetection of JNK and p38 phosphoproteins in the
      Tg2576 mouse compared with wild type controls confirmed these findings. The
      significant increase in co-immunoprecipitation of p-JNK, p-p38 and Rac1 proteins
      with cdk5 in the transgenic mouse provided evidence for these interactions. At
      the cellular level, p-JNK and cdk5 colocalized in the cytoplasm of the cell
      bodies and neurites of brain cortical areas of the transgenic mouse. The present
      evidence suggests a cellular link between the cdk5 system and the stress kinase
      JNK and p38 pathways in an in vivo model. This study sheds new light on the
      pathogenesis of neuronal degeneration processes such as those occurring in
      Alzheimer's disease.

PMID- 14663201
TI  - Regional pattern of binding and c-Fos induction by (R)- and (S)-citalopram in rat
      brain.
AB  - Citalopram is a racemic mixture of two stereoisomers, (R)- and (S)-citalopram.
      Both enantiomers were radiolabelled and used for in vitro receptor
      autoradiography in rat brain. High levels of specific [3H](S)-citalopram binding
      were observed in the amygdala complex, substantia nigra, superior colliculus and
      central grey. No specific binding of [3H](R)-citalopram was observed in any brain
      regions examined. S-citalopram induced a significant increase in c-Fos positive
      cells in central amygdala and in the bed nucleus of the stria terminalis (BST),
      compared to vehicle controls. A similar pattern of c-Fos activation was observed
      with (RS)-citalopram, sertraline and paroxetine, while (R)-citalopram did not
      increase c-Fos expression in these areas. The high affinity binding and apparent
      neuronal activation by (RS)-citalopram is thus confined to the (S)-enantiomer.

PMID- 14663202
TI  - Glycogen synthase kinase-3 beta is highly activated in nuclei and mitochondria.
AB  - Glycogen synthase kinase-3 beta (GSK3 beta) is located predominantly in the
      cytosol, but also is in nuclei and mitochondria. In SH-SY5Y cells, primary
      cortical neurons, and mouse brain, the portion of active GSK3 beta (not
      phosphorylated on serine-9) was 5- to 8-fold greater in nuclei and mitochondria
      than in cytosol. Correspondingly greater GSK3 beta activities were measured in
      nuclei and mitochondria compared with cytosol. Stimulation of apoptotic signaling
      by treatment with camptothecin or thapsigargin activated GSK3 beta in the nucleus
      and mitochondria, but not the cytosol, whereas inhibition of GSK3 beta by lithium
      treatment affected all three pools of GSK3 beta. Thus, the nuclei and
      mitochondria contain disproportionately high levels of active GSK3 beta, which is
      selectively further activated by some apoptotic stimuli.

PMID- 14663203
TI  - Ca2+-ATPase isoforms are expressed in neuroprotection in rat, but not human,
      neurons.
AB  - Glutamate excitotoxicity has been implicated in neuronal death and damage in many
      neurodegenerative disorders. The potential neuroprotective role of the plasma
      membrane calcium ATPase (PMCA) and the NMDA receptor were investigated in rat and
      human brain neurons after a glutamate insult. Investigation of potential
      mechanisms of neuronal survival revealed that surviving rat cerebellar granule
      cells expressed the mRNA of new PMCA isoforms 2b and 2c. There was no observable
      change in expression of PMCA isoforms or NMDA receptor NR2 subtypes in human
      cortical neurons. This study shows that subsets of rat and human neurons are
      resistant to glutamate-induced excitotoxicity and the mechanisms employed to
      enable survival differ between rat and human neurons.

PMID- 14663204
TI  - Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone.
AB  - Mitochondrial complex I activity is partially suppressed in patients with
      Parkinson's disease, which is characterized by dopaminergic neuronal death.
      However, the precise relationship between neuronal death and mitochondrial
      complex I suppression has been unresolved. We investigated the involvement of
      superoxide and endogenous dopamine in neurotoxicity by rotenone, a complex I
      inhibitor. A short exposure to rotenone at high concentrations reduced the
      viability of both dopaminergic and non-dopaminergic neurons. The toxicity was
      significantly prevented by a membrane-permeable superoxide dismutase mimetic and
      alpha-methyl-p-tyrosine (alpha-MT), a tyrosine hydroxylase inhibitor. Chronic
      treatment with low-concentration rotenone caused selective toxicity to
      dopaminergic neurons, and this toxicity was attenuated by alpha-MT. These data
      suggest that superoxide and endogenous dopamine play an important role in
      dopaminergic neuronal loss.

PMID- 14663205
TI  - Effects of haloperidol and clozapine on Fos expression in the primate striatum.
AB  - In cynomolgus monkeys, the typical neuroleptic haloperidol induced strong
      expression of the immediate early gene product Fos in both the nucleus accumbens
      shell and the dorsal striatum. In the caudate nucleus, haloperidol induced
      staining was more marked in the striosomes than the matrix. The atypical
      neuroleptic clozapine also induced Fos expression in the nucleus accumbens, but,
      in contrast to haloperidol, had only a small effect in the dorsal striatum.
      Additionally, clozapine was more potent than haloperidol at inducing Fos-like
      immunoreactivity in the islands of Calleja. These results are similar to those
      typically obtained in rodents, and suggest that the basic mechanisms underlying
      the regional specificity of the effects of atypical neuroleptics are likely be
      conserved between these two mammalian orders.

PMID- 14663206
TI  - Repeated morphine injections induce behavioural sensitization in Roman high- but
      not in Roman low-avoidance rats.
AB  - The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for,
      respectively, rapid vs poor active avoidance acquisition has resulted in two
      phenotypes that differ in their behavioural and neurochemical responses to
      addictive drugs, including morphine. To compare the ability of these lines to
      develop behavioural sensitization to morphine, female RHA and RLA rats were
      treated twice daily with either saline or escalating doses of morphine (5, 10,
      and 20 mg/kg, s.c. on the 1st, 2nd, and 3rd day of treatment, respectively), and
      were challenged with morphine (0.5 or 2 mg/kg, s.c.) 1 day before and 3 weeks
      after repeated morphine administration. The locomotor activation produced by
      either challenge dose of morphine was more pronounced in RHA rats repeatedly
      treated with morphine vs the respective saline-treated controls, whereas no
      significant change in locomotor activity was observed in RLA rats. The results
      show that behavioral sensitization to morphine was induced in RHA but not in RLA
      rats.

PMID- 14663207
TI  - 3-OH-pip-BTCP, a metabolite of the potent DA uptake blocker BTCP, exerts cocaine
      like action in rats.
AB  - A previous study showed that N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidin-3-ol
      (3-OH-pip-BTCP), an active metabolite of the potent dopamine reuptake inhibitor N
      [1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP), exhibits stimulant effects
      in rats (i.e. increases dopamine levels in the nucleus accumbens and increases
      locomotion). The present study sought to further characterize the behavioral
      profile of 3-OH-pip-BTCP, specifically, its interaction with cocaine-maintained
      behavior. Cocaine self-administration was examined in 3-OH-pip-BTCP pretreated
      rats. 3-OH-pip-BTCP (0-20 mg/kg, i.p.) dose-dependently decreased cocaine self
      administration. Additionally, 3-OH-pip-BTCP (10 mg/kg) shifted the cocaine dose
      response to the left. Together, these results suggest that 3-OH-pip-BTCP shares
      similar reinforcing effects with cocaine and therefore may serve as a
      substitutive drug and possible agonist therapy for cocaine addiction.

PMID- 14663208
TI  - Glutamate-dependent regulation of cholinergic phenotype in hypothalamic neurons.
AB  - Glutamate NMDA receptor antagonists are used clinically. However, they have
      serious side effects, some of which are presumably due to an increase in
      acetylcholine transmission. Our previous experiments revealed acetylcholine
      dependent excitation in rat hypothalamic cultures after a chronic glutamate
      receptor blockade. Dextromethorphan, amantadine, and eliprodil are NMDA receptor
      antagonists. Lamotrigine inhibits synaptic glutamate release. These drugs are
      used clinically. Here, using calcium imaging and immunocytochemistry, we
      demonstrate that a chronic treatment with each of these drugs induced
      acetylcholine activity and choline acetyltransferase immunoreactivity in rat
      hypothalamic (but not cortical) cultures. These data support the possibility that
      some side effects of anti-glutamate drugs in vivo may be due to the increase in
      cholinergic properties in certain regions of the CNS.

PMID- 14663209
TI  - Fluoxetine blocks cloned neuronal A-type K+ channels Kv1.4.
AB  - The effects of fluoxetine were studied on cloned K+ channel Kv1.4 stably
      expressed in Chinese hamster ovary (CHO) cells using the whole-cell configuration
      of the patch-clamp technique. Extracellular application of various concentrations
      of fluoxetine inhibited the amplitude of the peak current of Kv1.4 and
      accelerated its inactivation time course in a concentration-dependent manner.
      Thus, fluoxetine decreased Kv1.4 (the integral of the outward current) in a
      concentration-dependent manner; the IC50 was 33.1 +/- 2.5 microM. The inhibitory
      effect of fluoxetine was time-dependent. The apparent association (k) and
      dissociation (l) rate constants measured at +40 mV were 3.5 +/- 0.7 microM-1s-1
      and 132.5 +/- 13.3 s-1, respectively. The Kd (= l/k) was 37.9 microM, which was
      close to the value obtained from the concentration-response curve. The block
      produced by fluoxetine increased steeply between -30 and 0 mV, which corresponded
      with the voltage range for channel opening. The fluoxetine block was constant at
      more depolarized potentials, suggesting that the block by fluoxetine was not
      voltage dependent. Our data indicate that fluoxetine blocks Kv1.4 channels by
      preferentially binding to open state.

PMID- 14663210
TI  - Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity
      in rat hippocampal cultures.
AB  - The neuroprotective effect of docosahexaenoic acid (DHA) on the glutamate-induced
      cytotoxicity in rat hippocampal cultures was investigated in the present study.
      DHA at 5-50 microg/ml successfully protected neurons against the cytotoxicity,
      markedly increased the cell viability, inhibited both nitric oxide (NO)
      production and calcium influx, and increased the activities of antioxidant
      enzymes of glutathione peroxidase (GSH-Px) and glutathione reductase (GR).
      However, it did not alter the levels of glutathione (GSH) as compared to the
      control. These results suggest that DHA might be a potent neuroprotector. In
      addition, they may help to improve our understanding of the effect of DHA on
      neurodegeneration.

PMID- 14663211
TI  - Guanosine promotes myelination and functional recovery in chronic spinal injury.
AB  - Functional loss after spinal cord injury (SCI) is caused, in part, by
      demyelination of axons surviving the trauma. Administration of guanosine (8
      mg/kg/day, i.p.) for 7 consecutive days, starting 5 weeks after moderate SCI in
      rats, improved locomotor function and spinal cord remyelination. Myelinogenesis
      was associated with an increase in the number of mature oligodendrocytes detected
      in guanosine-treated spinal cord sections in comparison with controls. These data
      indicate that guanosine-induced remyelination resulted, at least in part, from
      activation of endogenous oligodendrocyte lineage cells. These findings may have
      significant implications for chronic demyelinating diseases.

PMID- 14663212
TI  - Sex differences in frontal lobe white matter microstructure: a DTI study.
AB  - There is evidence that the brains of men and women are structurally different,
      but there are few data regarding possible sex differences in white matter
      microstructure. Using diffusion tensor imaging we assessed fractional anisotropy
      (FA) in the frontal lobe white matter on contiguous 5 mm slices in nine healthy
      male and 11 healthy female adults. Overall, women had higher FA in the left
      frontal lobe compared to men and a leftward asymmetry of FA in contrast to men,
      who showed no hemispheric asymmetry. Among women, greater leftward asymmetry of
      frontal lobe FA correlated significantly with better verbal comprehension and
      memory functioning. Our findings may be indicative of increased directional
      coherence and/or density of left hemisphere white matter fibers and a leftward
      asymmetry of this structural integrity among women compared to men.

PMID- 14663213
TI  - Priming of new associations: a PET study.
AB  - Cognitive properties of associative priming are different from those of the non
      associative priming. We examined areas associated with associative priming to
      understand its cortical processing. After subjects had studied pairs of unrelated
      words, they were shown one of the studied words and a 3-letter word-stem that
      could be completed using either the word that was paired with the presented
      studied word (same context), or with a different word (different context). As
      compared to the fixation, both conditions elicited increased activations in the
      left prefrontal and decreased activation in the extrastriate cortex. Medial
      temporal lobe was activated only in the same-context condition. This finding
      helps to understand why associative priming is impaired in some amnesic patients.

PMID- 14663214
TI  - Errors in reward prediction are reflected in the event-related brain potential.
AB  - The error-related negativity (ERN) is a negative deflection in the event-related
      brain potential associated with error processing. A recent theory holds that the
      ERN is elicited by the impact of a reward prediction error signal carried by the
      mesencephalic dopamine system on anterior cingulate cortex. The theory predicts
      that larger ERNs should be elicited by unexpected unfavorable outcomes than by
      expected unfavorable outcomes. We tested the theory in an experiment in which the
      frequency of occurrence of reward was varied by condition, reasoning that the
      system that produces the ERN would come to expect non-reward when rewards were
      infrequent. Consistent with the theory, we found that larger ERNs were elicited
      by unexpected absences of reward.

PMID- 14663215
TI  - Cortisol has different effects on human memory for emotional and neutral stimuli.
AB  - Adrenal stress hormones are considered to play a role in memory enhancement of
      emotionally arousing events. To investigate the effects of cortisol on human
      emotional memory, subjects were administered hydrocortisone (25 mg) or placebo
      and presented with either an emotionally arousing or a neutral story. Memory for
      the story was tested 1 week later. In all memory tests, subjects who viewed the
      emotional story scored better for the emotionally arousing story parts,
      indicating that arousal enhances memory. In memory of details, cortisol showed an
      interaction with story valence but no main effect: cortisol enhanced memory for
      details of the neutral story version, but impaired memory for details of the
      emotionally arousing version. We thus confirm a non-linear interaction between
      cortisol and arousal on memory formation.

PMID- 14663216
TI  - Effects of brief discrimination-training on the auditory N1 wave.
AB  - We determined whether the human N1 evoked by tones with different frequencies
      might be affected by a brief discrimination-training at one specific frequency.
      During 1 h training, subjects learned to discriminate a 1062 Hz tone from another
      tone. Before and after training, subjects heard for 26 min tones with a frequency
      of 1000 Hz, replaced every sixth one by test tones with frequencies randomly and
      equiprobably chosen as 835, 886, 941, 1000, 1062, 1128 or 1198 Hz. The N1 to the
      test tone was larger when its frequency was further from the repeating frequency.
      After training N1 s were attenuated to all tones except the trained and repeated
      ones, indicating a refractory frequency effect, long-term habituation, and
      sensitization to the repeated and trained tones.

PMID- 14663218
TI  - Upper labial deficiency in Mobius syndrome: a previously unreported feature and
      its correction.
AB  - Bilateral facial palsy in Mobius syndrome remains one of the greatest challenges
      in reconstructive plastic surgery. Facial reanimation is an invaluable aid to
      such patients because it allows for greater social interaction by means of the
      ability to smile. In performing facial reanimation surgery on patients with
      Mobius syndrome, it is the observation of the senior author (Harrison) that upper
      labial deficiency is a consistent and previously unreported feature of the
      syndrome. It has been the practice of the senior author to perform upper labial
      augmentation on Mobius syndrome patients by insertion of a lipodermal autograft,
      in addition to facial reanimation. Nine patients with Mobius syndrome who
      presented to the Department of Plastic Surgery during an 8-year period were
      reviewed. All nine possessed bilateral facial palsy and upper labial deficiency
      in addition to other abnormalities consistent with Mobius syndrome. Six patients
      underwent bilateral facial reanimation and upper labial augmentation alone. One
      patient refused facial reanimation surgery but consented to upper labial
      augmentation. One patient, with concomitant micrognathia, underwent bilateral
      facial reanimation, upper labial augmentation, and insertion of a Silastic chin
      implant. In one patient, a child who also exhibited micrognathia, bilateral
      facial reanimation alone was carried out, with further procedures for upper
      labial and chin cosmesis being postponed until adulthood. The indication for
      performing upper labial augmentation was cosmetic. The procedure improved upper
      labial appearance and restored balance to the mouth. Patients also expressed
      higher satisfaction with eating and drinking, which they related to the improved
      fullness of the upper lip. This was before the facial reanimation had become
      functional. Upper labial deficiency warrants addition to the list of facial
      features of Mobius syndrome and is something that must be assessed in the context
      of facial reanimation surgery.

PMID- 14663217
TI  - An outcome evaluation of sphincter pharyngoplasty for the management of
      velopharyngeal insufficiency.
AB  - Sphincter pharyngoplasty is frequently used for the management of children with
      velopharyngeal insufficiency. The purpose of this study was to evaluate outcome
      and revision rates of sphincter pharyngoplasty at the authors' institution. Two
      hundred fifty patients underwent sphincter pharyngoplasty for velopharyngeal
      insufficiency between January of 1987 and March of 2001. There were 117 female
      patients and 133 male patients, with a mean age at primary sphincter
      pharyngoplasty of 7.6 years (range, 1 to 45 years). Diagnoses included
      velopharyngeal insufficiency alone (n = 63), velopharyngeal insufficiency
      associated with cleft palate (n = 127), velocardiofacial syndrome (n = 32),
      submucous cleft (n = 15), and other (n = 13). Pharyngoplasty revision was defined
      as any secondary surgical revision of the sphincter as determined by clinical
      evaluation and objective speech assessment. The pharyngoplasty revision rate was
      found to be 12.8 percent (n = 32). A favorable outcome was demonstrated in 30 of
      these patients (93.8 percent) after pharyngoplasty revision. Two patients, one
      with a diagnosis of a submucous cleft and velocardiofacial syndrome and the other
      with a cleft palate, required a second revision because of persistent
      velopharyngeal insufficiency. The revision rate was highest in those patients
      with velocardiofacial syndrome (21.8 percent) and lowest in patients with
      velopharyngeal insufficiency alone (6.3 percent). Patients who required revision
      had significantly higher preoperative oral sentence nasometry (55.2 percent
      versus 46.1 percent; p < 0.01) and larger velopharyngeal areas (23.7 mm2 versus
      18.9 mm2). There was no significant difference in age or sex for those patients
      who required a revision compared with those who did not require revision. Mean
      follow-up was 2.4 years (range, 4 months to 13.6 years). Sphincter pharyngoplasty
      is an effective procedure for the treatment of velopharyngeal insufficiency using
      revision rate as the standard of success. It had an 87 percent primary success
      rate that increased to 99 percent after a single revision. Patients with
      velocardiofacial syndrome, more severe preoperative hypernasal resonance, and
      larger velopharyngeal areas were more likely to require pharyngoplasty revision.

PMID- 14663219
TI  - Optimizing autologous breast reconstruction in thin patients.
AB  - Breast reconstruction with a transverse rectus abdominis myocutaneous (TRAM) flap
      plus an implant has been proposed as an option for women with a thin body habitus
      who do not have sufficient abdominal tissue to permit reconstruction with a TRAM
      flap alone. The standard autologous tissue reconstructive procedure in these
      women is a combined latissimus dorsi myocutaneous flap and breast implant. We
      reviewed our experience performing TRAM flap/implant and latissimus dorsi
      flap/implant breast reconstruction to compare complication rates and aesthetic
      outcomes between these two types of reconstruction. Between 1992 and 1999, 88
      breasts were reconstructed at our institution using an autologous tissue flap
      combined with a breast implant (44 with a TRAM flap/implant and 44 with a
      latissimus dorsi flap/implant). Recipient-site and donor-site complications for
      the two procedures were compared using Fisher's exact test; a panel of unbiased,
      blinded judges compared the aesthetic outcomes. The recipient-site complication
      rate was lower for the TRAM flap/implant group than for the latissimus dorsi
      flap/implant group (18 percent versus 34 percent, p = 0.09). Most recipient-site
      complications in the TRAM flap/implant group were related to fluid collection
      around the implant. In the TRAM flap/implant group, complications occurred in 37
      percent of the reconstructions that had immediate implant placement and in none
      of the reconstructions with delayed implant placement (p = 0.01). In the TRAM
      flap/implant reconstructions with immediate implant placement, the recipient-site
      complication rate was 50 percent when implants were completely filled with
      saline, but no complications occurred with incompletely filled, postoperatively
      adjustable implants (p = 0.03). No microvascular complications occurred with
      immediate placement of breast implants under TRAM flaps. Donor-site complications
      included a hematoma, a seroma, and an umbilical necrosis in the TRAM flap/implant
      group and six cases of seroma formation in the latissimus dorsi flap/implant
      group. The comparison of aesthetic outcome was statistically significant for the
      TRAM flap/implant group, which had a higher overall mean score than the
      latissimus dorsi flap/implant group did (3.29 versus 2.85, p = 0.01). The results
      of this study suggest that the TRAM flap/implant breast reconstruction should be
      considered as an alternative to the latissimus dorsi flap/implant breast
      reconstruction in women with a thin body habitus.

PMID- 14663220
TI  - Progressive tension sutures to prevent seroma formation after latissimus dorsi
      harvest.
AB  - The latissimus dorsi muscle flap is a versatile flap used in a variety of
      reconstructive procedures. The major complication reported with its use is donor
      site seroma, reported to occur in 20 to 79 percent of cases. A retrospective
      review of 47 patients undergoing latissimus dorsi muscle harvest from April of
      1998 through May of 2002 was performed. Progressive tension sutures were used
      during donor-site closure in 22 patients from March of 2000 through May of 2002.
      This group was compared with historical controls from April of 1998 through March
      of 2000 (n = 23) who underwent latissimus dorsi harvest without use of the
      technique. Seven of 23 controls (30 percent) developed seromas at the donor site,
      compared with 0 of 22 (Fisher's exact text, p = 0.0092). The authors conclude
      that use of progressive tension sutures placed at the time of donor-site closure
      is an effective method to reduce or eliminate the most common complication
      associated with latissimus dorsi harvest. Technique recommendations are reviewed.

PMID- 14663221
TI  - Pilomatrixoma: a review of 346 cases.
AB  - Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a benign skin
      neoplasm that arises from hair follicle matrix cells. Pilomatrixoma is a common
      skin neoplasm in the pediatric population that is often misdiagnosed as other
      skin conditions. This study reviews an 11-year experience at a tertiary
      children's hospital, examining the cause, clinical and histopathological
      presentation, management, and treatment outcomes of pilomatrixoma. A review of
      the pathology database at Children's Hospital Los Angeles revealed 346
      pilomatrixomas excised from 336 patients between 1991 and 2001. The hospital
      charts, pathology records, and plastic surgery clinic charts were reviewed with
      respect to variables such as sex, age at the time of presentation, clinical and
      histopathological presentation, preoperative diagnosis, management, recurrence,
      and treatment outcome. The main presenting symptom was a hard, subcutaneous,
      slowly growing mass. The preoperative diagnosis was accurate and consistent with
      the pathological diagnosis of pilomatrixoma in only 100 cases (28.9 percent).
      This entity should be considered with other benign or malignant conditions in the
      clinical differential diagnosis of solitary firm skin nodules, especially those
      on the head, neck, or upper limbs. The diagnosis can generally be made with a
      clinical examination. Imaging studies are not required unless symptoms or the
      location of the lesion warrants such diagnostic assessments. The treatment of
      choice is surgical excision, and the recurrence rate is low.

PMID- 14663222
TI  - Angiosome territories of the nerves of the lower limbs.
AB  - This anatomical study involved the meticulous dissection of three fresh cadaveric
      specimens to characterize the vascular supply of the nerves of the lower limb.
      The findings demonstrated that the nerves were supplied segmentally by source
      vessels, which were color-coded to match the corresponding angiosomes. The
      segments were then classified into five categories according to whether the
      nerves and source vessels were branched or unbranched, which has clinical
      relevance for harvesting of nerves for vascularized nerve transfers.

PMID- 14663223
TI  - Angiosomes of the brachial plexus: an anatomical study.
AB  - This anatomical study analyzed the neurovascular relationships of the brachial
      plexus. Ten fresh cadaveric brachial plexuses were examined after injection of
      the arterial system. The vascular anatomical features of the brachial plexus were
      documented with microdissection after lead oxide/gelatin injection. The specimens
      were analyzed by using radiography (including digital subtraction techniques) and
      light-microscopic, macroscopic, and digital photography. Four angiosomes, based
      on the subclavian, axillary, vertebral, and dorsal scapular arteries, were
      observed. As noted in previous angiosome studies, connections between angiosome
      territories lay within tissues, in this case, nerve trunks. Nutrient vessels
      penetrated nerve trunks at points of branching within the brachial plexus, with a
      Y-shaped mode of division on entry. The vascular supply was markedly rich, often
      with true anastomotic connections occurring within the nerves. There was much
      variation in supply, depending on the vascular anatomical features of the
      subclavian artery.

PMID- 14663225
TI  - Musculotendinous anomalies in musician and nonmusician hands.
AB  - Musculoskeletal abnormalities of musicians' hands and upper extremities are well
      recognized and potentially career-threatening problems. Of the many types of
      potentiality problematic musculoskeletal disorders that could be assessed, this
      study focused on joint instability and musculotendinous anomalies. For this
      study, the hands of 92 music students were compared with the hands of 64
      nonmusician control subjects. Flexor anomalies were observed much more frequently
      than extensor musculotendinous anomalies; clinical evidence of the Linburg
      Comstock anomaly was noted for 60 to 70 percent of subjects in both groups.
      Further analysis of the Linburg-Comstock anomaly demonstrated that the sites of
      pain among test-positive subjects were variable, test positivity was more
      frequent in the left hand and among string players, and test positivity tended to
      decrease from the radial side to the ulnar side of the hand. There were only two
      definite extensor musculotendinous anomalies (1.3 percent), and both involved a
      subluxating extensor mechanism affecting the little fingers. Forty-three percent
      of all subjects exhibited a degree of instability affecting the joints of their
      hands.

PMID- 14663224
TI  - COX-2 up-regulation in idiopathic carpal tunnel syndrome.
AB  - The objective of this study was to determine whether cyclooxygenase-2 (COX-2) is
      up-regulated in the synovium of patients with carpal tunnel syndrome. Twenty
      patients were enrolled: 16 consecutive patients with carpal tunnel syndrome and
      four control patients (exploration for non-carpal tunnel syndrome-related wrist
      or forearm pathology). Clinical data (demographics, pertinent history,
      symptomatology) were obtained preoperatively. Flexor tenosynovial tissue was
      isolated from all patients and clinically graded as thin, intermediate, or thick.
      Histologic evaluation was conducted to rule out the presence of inflammatory
      cells. Immunohistochemical staining for COX-2 was performed. The
      immunohistochemical data were confirmed by reverse transcriptase-polymerase chain
      reaction analysis of COX-2 mRNA. Results showed that the majority of carpal
      tunnel syndrome specimens (88 percent) showed synovial hypertrophy compared with
      0 percent of the controls (p < 0.05). Also, 69 percent of carpal tunnel syndrome
      specimens (11 of 16) versus 0 percent of controls (zero of four) stained
      positively for COX-2 (p < 0.05). Of the carpal tunnel syndrome patients, 91
      percent of thick specimens versus 33 percent of intermediate specimens versus 0
      percent of thin specimens showed COX-2 staining. The authors conclude that
      synovial hypertrophy is a prominent finding in carpal tunnel syndrome. COX-2 is
      up-regulated in the tenosynovium of patients with carpal tunnel syndrome, and
      this upregulation may correlate with the clinical grade of the tenosynovium. The
      role of COX-2 in carpal tunnel syndrome may be to mediate remodeling of
      pathologic tissue. To this end, it may be a potential therapeutic target for
      specific inhibition.

PMID- 14663226
TI  - Tissue carbon dioxide tension: a putative specific indicator of ischemia in
      porcine latissimus dorsi flaps.
AB  - Free flap surgical procedures are technically challenging, and anastomosis
      failure may lead to arterial or venous occlusion and flap necrosis. To improve
      myocutaneous flap survival rates, more reliable methods to detect ischemia are
      needed. On the basis of theoretical considerations, carbon dioxide tension,
      reflecting intracellular acidosis, may be suitable indicators of early ischemia.
      It was hypothesized that tissue carbon dioxide tension increased rapidly when
      metabolism became anaerobic and would be correlated with acute venoarterial
      differences in lactate levels, potassium levels, and acid-base parameters.
      Because metabolic disturbances have been observed to be less pronounced in flaps
      with venous occlusion, it was hypothesized that tissue carbon dioxide tension and
      venoarterial differences in lactate and potassium levels and acid-base parameters
      would increase less during venous occlusion than during arterial occlusion. In 14
      pigs, latissimus dorsi myocutaneous flaps were surgically isolated, exposed to
      acute ischemia for 150 minutes with complete arterial occlusion (seven subjects)
      or venous occlusion (seven subjects), and reperfused for 30 minutes. After
      arterial occlusion, pedicle blood flow decreased immediately to less than 10
      percent of baseline flow. Blood flow decreased more slowly after venous occlusion
      but within 3 minutes reached almost the same low levels as observed during
      arterial occlusion. Venous oxygen saturation decreased from approximately 70
      percent to approximately 20 percent, whereas oxygen uptake was almost arrested.
      Tissue carbon dioxide tension increased to two times baseline values in both
      groups (p < 0.01). The venoarterial differences in carbon dioxide tension, pH,
      base excess, glucose levels, lactate levels, and potassium levels increased
      significantly (p < 0.01). Tissue carbon dioxide tension measured during the
      occlusion period were closely correlated with venoarterial differences in pH,
      base excess, glucose levels, lactate levels, and potassium levels (median r2,
      0.67 to 0.92). After termination of arterial or venous occlusion, more pronounced
      hyperemia was observed in the arterial occlusion group than in the venous
      occlusion group (p < 0.05). Oxygen uptake (p < 0.05) and venoarterial differences
      in lactate and potassium levels (p < 0.05) were significantly more pronounced in
      the arterial occlusion group. In the venous occlusion group, with less pronounced
      hyperemia, venoarterial differences in acid-base parameters remained
      significantly different from baseline values before occlusion (p < 0.01). The
      data indicate that tissue carbon dioxide tension can be used to detect anaerobic
      metabolism, caused by arterial or venous occlusion, in myocutaneous flaps. The
      correlations between carbon dioxide tension and venoarterial differences in acid
      base parameters were excellent. Because carbon dioxide tension can be measured
      continuously in real time, such measurements are more likely to represent a
      clinically useful parameter than are venoarterial differences.

PMID- 14663227
TI  - Dose-dependent effects of FK506 on neuroregeneration in a rat model.
AB  - This study explored the effects of different doses of FK506 on peripheral nerve
      regeneration, to determine whether neuroregeneration could be enhanced without
      the toxicity of systemic immunosuppression. In the first part of the study,
      subimmunosuppressive doses of FK506 were determined by examining skin allograft
      survival in a rat model. Full-thickness skin grafts (2 cm2) from Wistar rats were
      grafted to recipient Lewis rats. The procedure was performed for six groups (n =
      6). The control group received no FK506, and the other five groups received daily
      doses of FK506 of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg. Animals that received 2.0
      mg/kg FK506 per day exhibited complete skin graft take, whereas all other groups
      demonstrated complete rejection. After determination of the immunosuppressive
      dose of FK506, the neuroregenerative effects of different doses of FK506 were
      explored by assessing nerve regeneration in 80 rats after tibial nerve
      transection and repair. The control group received no FK506, whereas the other
      four groups were given daily doses of FK506 of 0.25, 0.5, 1.0, or 2.0 mg/kg. Rats
      were euthanized at three time points (25, 30, and 35 days), to fully investigate
      the effects of different FK506 dosing regimens on neuroregeneration.
      Histomorphometric analyses performed on postoperative days 30 and 35 demonstrated
      statistically significant improvements in neuroregeneration with
      subimmunosuppressive FK506 doses of 0.5 and 1.0 mg/kg per day. Therefore, the
      study demonstrated that neuroregeneration was enhanced at low doses of FK506 that
      were not sufficient to prevent skin allograft rejection.

PMID- 14663228
TI  - Ex vivo gene therapy in autologous critical-size craniofacial bone regeneration.
AB  - In therapeutic bone repairs, autologous bone grafts, conventional or vascularized
      allografts, and biocompatible artificial bone substitutes all have their
      shortcomings. The bone formed from peptides [recombinant human bone morphogenetic
      proteins (BMPs)], demineralized bone powder, or a combination of both is small in
      size. Tissue engineering may be an alternative for cranial bone repair. In this
      study, the authors developed an animal model to test the hypothesis that
      replication-defective, adenovirus-mediated human BMP-2 gene transfer to bone
      marrow stromal cells enhances the autologous bone formation for repairing a
      critical-size craniofacial defect. The mesenchymal stromal cells of miniature
      swine were separated from the iliac crest aspirate and expanded in monolayer
      culture 1 month before implantation. The cultured mesenchymal stromal cells were
      infected with recombinant, replication-defective human adenovirus BMP-2, 7 days
      before implantation. Bilateral 2 x 5-cm2 cranial defects were created, leaving no
      osteogenic periosteum and dura behind. Mesenchymal stromal cells at 5 x 10(7)/ml
      were mixed with collagen type I to form mesenchymal stromal cell/polymer
      constructs. Mesenchymal stromal cells used for the control site were infected
      with adenovirus beta-Gal under the same conditions. After 6 weeks and 3 months,
      10 miniature swine were euthanized and the cranium repair was examined. Near
      complete repair of the critical-size cranial defect by tissue-engineered
      mesenchymal stromal cell/collagen type I construct was observed. The new bone
      formation area (in square centimeters) measured by three-dimensional computed
      tomography demonstrated that the improvement from 6 weeks to 3 months was
      significantly greater on the experimental side than on the control side (2.15 cm2
      versus 0.54 cm2, p < 0.001) and significantly greater at 3 months than at 6 weeks
      (2.13 cm2 versus 0.52 cm2, p < 0.001). The difference between the experimental
      and control groups was significant at 3 months (mean difference, 2.13 cm2; p <
      0.001). The maximal compressive strength of the new bone was similar to that of
      the normal cranial bone when evaluated by biomechanical testing (cranium bone
      versus tissue-engineered bone, 88.646 +/- 5.121 MPa versus 80.536 +/- 19.302 MPa;
      p = 0.227). Adenovirus was absent from all constructs by immunochemical staining
      at 6 weeks and 3 months after implantation. The successful repair of cranial
      defects in this experiment demonstrates the efficacy of the integration of the
      autologous stem cell concept, gene medicine, and polymers in producing tissue
      engineered bone.

PMID- 14663229
TI  - Free TRAM flap breast reconstruction after abdominal liposuction.

PMID- 14663230
TI  - Aesthetically precise templates for nasal reconstruction using a new material.

PMID- 14663231
TI  - Clinical experience with orbicularis oculi myocutaneous flaps in the temporal
      area.

PMID- 14663232
TI  - Nipple-areola reconstruction with a dermal-fat flap: technical improvement from
      rolled auricular cartilage to artificial bone.

PMID- 14663233
TI  - Reevaluation of the technique of toe-to-hand transfer for traumatic digital
      amputations in children and adolescents.

PMID- 14663234
TI  - Microdissected thin perforator flaps: 46 cases.

PMID- 14663235
TI  - Assessing surgical skill.

PMID- 14663236
TI  - Velopharyngeal incompetence: a guide for clinical evaluation.
AB  - Various causes of velopharyngeal disorders and the myriad of diagnostic methods
      used by speech-language pathologists and plastic surgeons for assessment are
      described in this article. Velopharyngeal incompetence occurs when the velum and
      lateral and posterior pharyngeal walls fail to separate the oral cavity from the
      nasal cavity during speech and deglutination. The functional goals of cleft
      palate operations are to facilitate normal speech and hearing without interfering
      with the facial growth of a child. Basic and helpful techniques are presented to
      help the cleft palate team identify preoperative or postoperative velopharyngeal
      incompetence. This information will enable any member of the multidisciplinary
      cleft palate team to better assist in the differential diagnosis and management
      of patients with speech disorders.

PMID- 14663237
TI  - Role of new fillers in facial rejuvenation: a cautious outlook.

PMID- 14663238
TI  - The tear "TROUF" procedure: transconjunctival repositioning of orbital
      unipedicled fat.
AB  - Aging of the lower lid and cheek results in bulging of orbital fat and deepening
      of the orbital rim groove, known as the "tear trough." As an alternative to
      orbital fat excision, pedicles of fat can be spread in a submuscular plane to
      obliterate the groove of the tear trough. In a 1-year period, 25 patients had
      correction of their tear trough deformities through a transconjunctival approach.
      This technique included incision of the septum near the arcus marginalis,
      dissection of a suborbicularis pocket, and placement of medial and central fat
      pedicles over the orbital rim with buried 5-0 plain gut sutures. Clinically,
      after a follow-up of 17 to 31 months, there was leveling of the tear trough,
      smooth contour of the lower lid and cheek, minimal complications, and high
      patient satisfaction.

PMID- 14663239
TI  - The high-superficial musculoaponeurotic system technique in facial rejuvenation:
      an update.
AB  - The medical charts of 267 patients who had primary high-superficial
      musculoaponeurotic system (SMAS) rhytidectomies were reviewed. The depth of the
      nasolabial fold was used as an indicator of the degree of descent of the
      subcutaneous cheek mass, as a guide in procedure selection, and as a method of
      judging the operative results. Fold depth was assigned a score of 0 to 3, with 3
      being most severe. According to their preoperative fold depth, patients were
      operated on using one of three variants of the high-SMAS technique: sub-SMAS
      dissection up to the nasolabial fold, sub-SMAS dissection up to the nasolabial
      fold plus transnasal SMAS graft, or sub-SMAS dissection across the nasolabial
      fold. An independent trained observer rated the postoperative fold depth in each
      case from photographs taken at the 6-month follow-up visit. Of patients with fold
      scores of 2 or 3, 97 percent (183 of 189 patients) showed visible improvement in
      nasolabial crease depth after the operation.

PMID- 14663240
TI  - Nipple or areolar reduction with simultaneous breast augmentation.
AB  - Patients requesting nipple or areolar reduction often desire simultaneous breast
      augmentation. A technique is described for implant placement by means of a nipple
      base incision with either nipple reduction or intraareolar reduction. Nipple
      reduction is accomplished by removing a ring of skin from the base of the nipple,
      while areolar reduction is performed by removing a donut-shaped area of skin
      whose inner diameter is at the nipple base. The elasticity of the areolar skin
      allows for access for saline implant placement. The resulting scar is well
      concealed. Results from 15 patients demonstrate that the technique is safe,
      practical, and appears to pose no increased risk of sensory changes to the
      nipple.

PMID- 14663241
TI  - Lumps and bumps: late postsurgical inflammatory and infectious lesions.
AB  - Late postsurgical infectious or inflammatory complications after facial surgery
      present a difficult challenge. These complications occur at least 2 weeks after
      surgical procedures and are often attributable to unique causes, in contrast to
      complications within the first postoperative week. The most worrisome
      complications in this period are caused by mycobacterial infections, because
      these infections can be severe and require a protracted treatment course. A high
      degree of suspicion is required early in presentation because these lesions can
      be subtle and similar to other infectious or inflammatory lesions. The authors
      discuss the clinical manifestations and diagnostic and treatment rationale for
      late postoperative infectious and inflammatory lesions. The authors also
      demonstrate and compare the clinical manifestations of mycobacterial infections,
      bacterial infections, and sterile inflammatory reactions. In addition, the
      treatment rationale for mycobacterial infections is reviewed. Late postoperative
      infections caused by mycobacteria are reported with increasing frequency in the
      cosmetic literature. These cases illustrate diverse challenges in the
      identification and treatment of late postoperative lesions.

PMID- 14663242
TI  - Septal extension grafts revisited: 6-year experience in controlling nasal tip
      projection and shape.

PMID- 14663244
TI  - Who decides the breast augmentation parameters?

PMID- 14663245
TI  - Recertification: now a reality.

PMID- 14663247
TI  - Just stop or just complain.

PMID- 14663248
TI  - Reconstruction of the columella in a pediatric patient.

PMID- 14663249
TI  - Chin augmentation with conchal cartilage.

PMID- 14663250
TI  - Buttock implants for male chest enhancement.

PMID- 14663251
TI  - About images with breast implants and galactocele.

PMID- 14663252
TI  - The electrocardiography dot as a preoperative marker for nipple-areola complex
      reconstruction.

PMID- 14663253
TI  - Measuring outcomes in aesthetic surgery.

PMID- 14663254
TI  - A simple method to stabilize the penis during operation.

PMID- 14663255
TI  - Compartment syndrome after substitution vaginoplasty: an onerous medical
      complication.

PMID- 14663256
TI  - Flap coverage requirement following muscle-sliding operation for moderate-type
      Volkmann contracture associated with poor skin quality on the forearm.

PMID- 14663257
TI  - Avoiding injury to the inferior oblique muscle during lower lid blepharoplasty.

PMID- 14663258
TI  - Bilateral elastofibroma as an unusual cause of shoulder pain.

PMID- 14663259
TI  - Treatment of mandible fractures using bioabsorbable plates.

PMID- 14663260
TI  - Reanimation options in patients with hemifacial microsomia and marginal
      mandibular nerve palsy.

PMID- 14663261
TI  - Autostatic syndrome in association with facial nerve transplantation.

PMID- 14663262
TI  - Medial pedicled orbicularis oculi flap.

PMID- 14663263
TI  - Effect of ultrasound-assisted liposuction on skin perfusion.

PMID- 14663264
TI  - Safer liposuction for hospital staff.

PMID- 14663265
TI  - Gestational gigantism after reduction mammoplasty.

PMID- 14663266
TI  - Ultrasound aspiration for gynecomastia.

PMID- 14663267
TI  - Effects of reduction mammaplasty on pulmonary function and symptoms of
      macromastia.

PMID- 14663268
TI  - Soft-tissue sarcoma arising from a tissue necrosis caused by an intramuscular
      injection of diclofenac.

PMID- 14663269
TI  - A rare case of dermoid cyst behind the ear.

PMID- 14663270
TI  - A new device: A portable and effective irrigation system for pressure ulcers.

PMID- 14663271
TI  - A double pocket for tissue expander implantation in breast reconstruction.

PMID- 14663273
TI  - "Beriberi" interesting!

PMID- 14663274
TI  - Sickle cell disease: from membrane pathophysiology to novel therapies for
      prevention of erythrocyte dehydration.
AB  - Sickle cell anemia is characterized by the presence of dense dehydrated
      erythrocytes that have lost most of their K content. Due to the unique dependence
      of Hb S polymerization on intracellular Hb S concentration, preventing this
      dehydration should markedly reduce polymerization. The erythrocyte intermediate
      conductance Ca-activated K channel (hSK4 or KCNN4), first described by Gardos,
      has been shown to be a major pathway for sickle cell dehydration. Studies with
      the imidazole antimycotic clotrimazole have shown reduction of sickle cell
      dehydration in vivo in a small number of patients with sickle cell disease; dose
      limiting gastrointestinal and liver toxicities were observed. Based on the
      chemical structure of clotrimazole metabolites, a novel Gardos channel inhibitor,
      ICA-17043, has been developed. It has shown substantial activity both in vitro
      and in vivo in transgenic sickle mice. ICA-17043 is currently in phase 2 human
      trials. Another potential therapeutic target is the K-Cl cotransport. When sickle
      erythrocytes are exposed to relatively acidic conditions, they undergo cell
      shrinkage via activation of this pathway. K-Cl cotransport can be blocked by
      increasing the abnormally low erythrocyte Mg content of sickle erythrocytes. Oral
      Mg supplementation has been shown to reduce sickle cell dehydration in vivo in
      transgenic sickle mice and in patients in two separate clinical trials. Oral Mg
      pidolate is being tested in clinical trials in homozygous sickle cell disease and
      in Hb S/HbC (SC) disease, either as a single agent or in combination with
      hydroxyurea. The ongoing trials will determine the clinical effectiveness of
      therapies aimed at preventing sickle erythrocyte dehydration.

PMID- 14663275
TI  - Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma
      treated with tandem double autologous stem cell transplants.
AB  - OBJECTIVE: To assess the efficacy and toxicity of local radiotherapy in achieving
      local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated
      with induction chemotherapy and tandem stem cell transplants. METHODS: Fifty-two
      children with stage 4 or high-risk stage 3 neuroblastoma were treated on a
      standardized protocol that included five cycles of induction chemotherapy,
      surgical resection of the primary tumor when feasible, local radiotherapy, and
      then consolidation with tandem myeloablative cycles with autologous peripheral
      blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to
      patients with gross or microscopic residual disease prior to the myeloablative
      cycles. Thirty-seven patients received local radiotherapy to the primary tumor or
      primary tumor bed. Two patients with unknown primaries each received radiotherapy
      to single, unresectable, bulky metastatic sites. The second of the myeloablative
      regimens included 12 Gy of total body irradiation. RESULTS: Of the 52
      consecutively treated patients analyzed, 44 underwent both transplants, 6
      underwent a single transplant, and 2 progressed during induction. Local
      radiotherapy did not prolong recovery of hematopoiesis following transplants, did
      not increase peritransplant morbidity, and did not prolong the hospital stay
      compared with patients who had not received local radiotherapy. Local control was
      excellent. Of 11 patients with disease recurrence after completion of therapy, 9
      failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1
      recurred 67 months following therapy in the previously bulky metastatic site that
      had been irradiated, and 1 had local recurrence concurrent with distant
      progression 15 months following the second transplant. The three-year event-free
      survival was 63%, with a median follow-up of 29.5 months. The actuarial
      probability of local control was 97%. CONCLUSIONS: The use of induction
      chemotherapy, aggressive multimodality therapy for the primary tumor, followed by
      tandem myeloablative cycles with stem cell transplant in patients with stage 4 or
      high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low
      local recurrence risk, and an improvement in survival.

PMID- 14663276
TI  - O6-methylguanine-DNA methyltransferase activity and promoter methylation status
      in pediatric rhabdomyosarcoma.
AB  - OBJECTIVES: To determine the activity of the DNA repair protein O6-methylguanine
      DNA methyltransferase (MGMT) and MGMT promoter methylation status of pediatric
      rhabdomyosarcoma (RMS) and examine MGMT in RMS tumors from different prognostic
      groups. METHODS: Fifteen samples each of the alveolar (ARMS) and embryonal (ERMS)
      subtypes were obtained for analysis of MGMT activity and promoter methylation
      status. MGMT activity was assayed by measuring the removal of O6-[3H]
      methylguanine from [3H]-methylated substrate by a tumor extract containing the
      enzyme. Promoter methylation status was examined using methylation-specific
      polymerase chain reaction (PCR). RESULTS: MGMT activity was successfully assayed
      from 25 samples, 10 ERMS and 15 ARMS. All ERMS and 11 of the 15 ARMS samples
      displayed high activity levels. There was significant intertumor variability
      among both subtypes but no significant difference in mean activity between the
      two histologic groups. There were trends toward increased activity in ERMS tumors
      and tumors from anatomically unfavorable locations. Only one tumor was
      hypermethylated at the MGMT promoter region. CONCLUSIONS: This analysis suggests
      that a low percentage of RMS samples are hypermethylated at the MGMT promoter and
      that most have significant MGMT activity, implying that clinical trials with MGMT
      modulating agents may have a role in the treatment of these tumors. This analysis
      does not support MGMT activity as an explanation of the differential response to
      chemotherapy demonstrated by ARMS and ERMS, but does suggest that MGMT may be
      involved in RMS treatment failure regardless of subtype and in the poorer
      response shown by tumors from unfavorable locations.

PMID- 14663277
TI  - Hematologic features and clinical course of an infant with Pearson syndrome
      caused by a novel deletion of mitochondrial DNA.
AB  - OBJECTIVE: Pearson bone marrow-pancreas syndrome (PS) is a rare, usually fatal
      mitochondrial disorder involving the hematopoietic system in early infancy. Due
      to the diversity of clinical symptoms, the diagnosis can be difficult. The
      authors describe a boy with severe hypoplastic anemia in whom extensive clinical,
      biochemical, and morphologic findings led to the diagnosis of PS, and molecular
      analysis revealed a novel deletion of mitochondrial DNA from nucleotide position
      10.371 to 14.607. METHODS: The patient is a 2-year-old boy who presented at age 5
      months with hypoplastic macrocytic anemia. His first months of life and the
      family history were uneventful. Extensive pretransfusion evaluations did not
      reveal a metabolic, infectious, or hematologic-neoplastic etiology, and he had no
      evidence of exocrine pancreatic insufficiency. However, a second bone marrow
      aspirate at age 7 months showed a reduced cell number, vacuolated erythroblasts
      and myeloblasts, and ringed sideroblasts, so PS was suspected. RESULTS:
      Additional molecular analysis from the boy's blood leukocytes revealed a deletion
      of mitochondrial DNA from nucleotide position 10.371 to 14.607, which was absent
      in his mother's blood cells, consistent with a sporadic mutation as commonly seen
      in PS. The muscle histology and the respiratory chain enzymes were normal.
      CONCLUSIONS: Mitochondriopathies should be considered in children with persistent
      non-neuromuscular symptoms such as unexplained refractory anemia. Due to the
      often-fatal course of PS, the rapid detection of mitochondrial DNA deletions is
      imperative for diagnosis and family counseling.

PMID- 14663278
TI  - High incidence of early cholelithiasis detected by ultrasonography in children
      and young adults with hereditary spherocytosis.
AB  - OBJECTIVES: Retrospective cholecystography studies in adults with hereditary
      spherocytosis (HS) suggested detectable gallstones in 37% to 43% of patients.
      Since longitudinal studies using biliary ultrasonography are unavailable, the aim
      of the present study was to determine the incidence of gallstone disease, as
      detected by biliary ultrasonography, in children and young adults with HS. As
      individuals with HS who co-inherit Gilbert syndrome have a greater risk of
      developing gallstones, uridine diphosphate-glucuronyl transferase (UGT-1A) gene
      polymorphism was also determined. PATIENTS AND METHODS: The authors
      retrospectively evaluated 44 patients aged 1.4 to 22 years with HS, 12 (27%) of
      whom underwent splenectomy. Ultrasonography was performed annually starting at
      the age of 4 years or at the time of diagnosis, if later. RESULTS: Of the 44
      patients, 18 (41%) developed cholelithiasis as demonstrated by gallbladder
      ultrasonography. In most patients (94%) the test first proved positive at age 4
      to 13 years. Patients with HS and Gilbert syndrome tended to be younger at the
      time of cholelithiasis. CONCLUSIONS: Early cholelithiasis was detected in
      children and young adults with HS. To identify this complication, the authors
      recommend early annual biliary ultrasonography in HS children, starting at about
      4 years of age. In patients with Gilbert syndrome, closer follow-up may be
      indicated.

PMID- 14663279
TI  - Etiology and outcome of graft failure in pediatric hematopoietic stem cell
      transplant recipients.
AB  - PURPOSE: To determine the incidence, etiology and outcome of graft failure in
      pediatric allogeneic bone marrow transplant (BMT) recipients. PATIENTS AND
      METHODS: Patients with primary or secondary graft failure were identified by
      database review. A retrospective chart review was performed. Etiologic factors
      were identified and assessed for statistical significance. RESULTS: 309 children
      underwent allogeneic BMT during the time interval studied. Four cases of primary
      graft failure and 7 cases of secondary graft failure occurred. Nonmalignant
      diagnosis, lower total nucleated cell (TNC) dose, and conditioning without total
      body irradiation were associated with a higher incidence of graft failure. Donor
      source, donor/recipient CMV status, CD34+ cell dose, and alloimmunization were
      not associated with graft failure. CONCLUSIONS: Graft failure is a relatively
      uncommon occurrence in pediatric patients. Autologous reinfusion may allow time
      to prepare the patient for a second transplant and decrease complications
      associated with aplasia. More immunosuppressive conditioning regimens may
      decrease the incidence of graft failure, particularly in patients with non
      malignant diseases or those with lower stem cell doses. More frequent monitoring
      of chimerism by VNTR analysis may detect late graft failure earlier and allow for
      more rapid intervention.

PMID- 14663280
TI  - Elevated serum interleukin-15 level in acute graft-versus-host disease after
      hematopoietic cell transplantation.
AB  - OBJECTIVE: To correlate serum cytokine levels and the development of acute graft
      versus-host disease (GVHD), the authors conducted a prospective study on serial
      measurements of interferon (IFN)-gamma and interleukin (IL)-10, IL-12 and IL-15.
      METHODS: The cytokines were measured in 27 subjects by enzyme-linked
      immunosorbent assay serially for the first 2 months after hematopoietic cell
      transplantation. RESULTS: Nineteen subjects with acute GVHD had significantly
      higher mean peak serum levels of IFN-gamma and IL-15 than the baseline levels at
      the start of conditioning. The peak level occurred soon after stem cell infusion
      and returned to the pretransplantation state in the second month. In contrast,
      there was lesser difference between the mean peak serum levels of IFN-gamma, IL
      10, and IL-15 and the baseline level in the eight subjects without GVHD. The peak
      serum level for IL-15 was, in addition, significantly higher among GVHD subjects
      than those without GVHD in the first month posttransplantation. However, the
      level of IL-15 showed no correlation with the severity of GVHD. CONCLUSIONS:
      These changes point to a possible role of systemic cytokine secretion in the
      development of acute GVHD. Elevated levels of IL-15 early in the posttransplant
      period could be a helpful laboratory predictor of acute GVHD.

PMID- 14663281
TI  - Severe lactic acidosis due to thiamine deficiency in a patient with B-cell
      leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate
      therapy.
AB  - An 11-month-old girl with B-cell leukemia/lymphoma developed profound lethargy
      due to severe lactic acidosis during chemotherapy and total parenteral nutrition
      (TPN). Initial treatment with NaHCO3 was ineffective. Treatment with a vitamin
      cocktail (OH-cobalamin, pyridoxine, thiamine, riboflavine, biotin, carnitine) at
      pharmacologic doses rapidly improved the child's clinical and laboratory status.
      Lactic acidosis was caused by an impairment of pyruvate dehydrogenase complex,
      which was due to lack of its necessary cofactor thiamine in the TPN. This case
      report indicates that lactic acidosis may be a front-line diagnosis in patients
      on TPN with lethargy and outlines the need for monitoring thiamine supply in TPN.

PMID- 14663282
TI  - Fatal pulmonary hemorrhage associated with micrococcal infection in two children
      with acute lymphoblastic leukemia.
AB  - Pulmonary hemorrhage is a rare cause of death in patients with acute leukemia.
      Within a 2-month period the authors observed two fatal pediatric cases, which
      were associated with opportunistic organisms of the genus Micrococcus. Both
      patients were receiving consolidation treatment for acute lymphoblastic leukemia.
      The authors discuss the causes of pulmonary hemorrhage in patients with leukemia
      and review the relevant literature. Micrococci have previously been considered as
      non-pathogenic, but there is considerable evidence for morbidity and mortality
      occurring, particularly in immunocompromised patients. The authors propose that
      micrococcal infection may have been a major predisposing factor for pulmonary
      hemorrhage in these thrombocytopenic patients.

PMID- 14663283
TI  - Isolated central nervous system (CNS) relapse in a case of childhood systemic
      anaplastic large cell lymphoma without initial CNS involvement.
AB  - Central nervous system (CNS) involvement in cases of anaplastic large cell
      lymphoma (ALCL) has been described only rarely. The authors describe an 11-year
      old girl with ALCL who developed isolated CNS relapse but had no CNS disease at
      initial diagnosis and had received CNS-prophylactic treatment. The patient
      achieved a second remission following intensive treatment of the relapse and
      continues to be in remission at the time of writing. This case serves to
      emphasize that isolated CNS relapse without detectable initial CNS involvement
      can arise even after CNS-prophylactic treatment in pediatric ALCL cases.

PMID- 14663284
TI  - Acute myocardial infarction in sickle cell anemia.
AB  - Cardiovascular dysfunction consistent with ischemia has been observed during
      episodes of painful crisis and following periods of heavy physical exertion in
      individuals with sickle cell disease. Similar findings have been observed in
      other individuals while taking the alpha-adrenergic agonist pseudoephedrine.
      However, acute myocardial infarction is extremely rare. The authors describe a
      case of sudden death in a child with sickle cell disease due to acute myocardial
      infarction and suggest that heavy exertional stress and use of pseudoephedrine
      may have precipitated the event.

PMID- 14663285
TI  - Possible allogeneic graft-versus-tumor effect in childhood melanoma.
AB  - Patients with metastatic melanoma have a very poor prognosis despite contemporary
      biochemotherapy. A 14-year-old girl with stage IV melanoma and brain metastasis
      received a nonmyeloablative conditioning and a hematopoietic graft from an HLA
      identical sibling. She had progression of disease in the first 2 months after
      transplantation. After withdrawal of immunosuppressant and establishment of a
      full donor chimeric status, peripheral disease response was documented by
      regression of metastatic disease and lack of tumor progression until 1 year after
      transplantation. She died of progressive disease 21 months after diagnosis and 17
      months after transplantation. Her clinical course suggested the possible
      existence of an allogeneic graft-versus-melanoma response that prolonged her
      survival.

PMID- 14663286
TI  - Non-Hodgkin lymphoma manifesting as thyroid nodules and cardiac involvement.

PMID- 14663287
TI  - The X-linked hyper-IgM syndrome: clinical and immunologic features of 79
      patients.
AB  - The X-linked hyper-IgM (XHIGM) syndrome is an uncommon primary immunodeficiency
      disease caused by mutations in the gene for CD40 ligand and characterized by
      normal or elevated serum IgM, reduced levels of IgG and IgA, and defective T-cell
      function. Because of its rarity, it has been difficult for any single
      investigator or institution to develop a comprehensive clinical picture of this
      disorder. Accordingly, a national registry was developed in the United States to
      provide demographic, genetic, immunologic, and clinical information on a
      relatively large number of patients with the XHIGM syndrome.A total of 79
      patients from 60 unrelated families were registered between January 1997 and July
      2002. The estimated minimal incidence was approximately 1/1,030,000 live births.
      All of the patients had significant IgG deficiency and most had IgA deficiency,
      but only one-half had elevated IgM levels. Most patients presented initially with
      a history of an increased susceptibility to infection including Pneumocystis
      carinii pneumonia. The average age of diagnosis was significantly earlier in
      patients born into a family with a previously affected individual. However, only
      one-third of the patients born into a family with a previously affected
      individual were diagnosed exclusively because of the presence of the positive
      family history before any clinical symptoms developed. Over half the patients
      developed symptoms of immunodeficiency and were diagnosed by 1 year of age, and
      over 90% by 4 years of age. The most prominent clinical infections were pneumonia
      (81% of patients), upper respiratory infections (49%) including sinusitis (43%)
      and recurrent otitis (43%), recurrent/protracted diarrhea (34%), central nervous
      system infections (14%), sepsis (13%), cellulitis (13%), hepatitis (9%), and
      osteomyelitis (1%). In addition to infections caused by encapsulated bacteria,
      opportunistic infections were relatively common and were caused by P. carinii,
      members of the herpes virus family (including cytomegalovirus), Cryptosporidium,
      Cryptococcus, Candida, Histoplasma, and Bartonella. Sclerosing cholangitis
      occurred in 5 patients and in 4 of these was associated with Cryptosporidium
      infection. Eight patients had died at the time of their entry into the Registry;
      2 of pneumonia (1 P. carinii and 1 cytomegalovirus), 2 of encephalitis (1 ECHO
      virus and 1 cytomegalovirus), 2 of malignancy (both hepatocellular carcinoma), 1
      of sclerosing cholangitis caused by Cryptosporidium, and 1 of hemolytic uremic
      syndrome.

PMID- 14663288
TI  - Etiologic diagnosis of 204 pericardial effusions.
AB  - The etiologic evaluation of pericardial effusion is frequently unsuccessful when
      noninvasive methods are used. To determine the cause of the current episode, all
      patients with echographically identified pericardial effusion from May 1998 to
      December 2002 underwent noninvasive diagnostic testing of blood, throat, and
      stool samples. Patients with postpericardiotomy syndrome were excluded. To
      analyze the value of our tests, we tested randomly selected blood donors as
      negative controls. Among 204 included patients, 107 (52.4%) had a final etiologic
      diagnosis: the etiology of 52 was highly suspected at first examination and later
      confirmed (thyroid deficiency, 5 cases; systemic lupus erythematous, 7;
      rheumatoid arthritis, 7; scleroderma, 3; cancer, 25; and renal insufficiency, 5).
      A definite etiologic diagnosis was made in 11 patients from pericardial fluid
      analysis (cancer, 5 cases; tuberculosis, 3; Streptococcus pneumoniae, Citrobacter
      freundii, and Actinomyces, 1 case each). Among 141 patients considered to have
      idiopathic pericarditis, 44 (32.1%) gained an etiologic diagnosis by our
      systematic testing strategy. This included serologic evaluation of serum
      (Coxiella burnetii, 10 cases; Bartonella quintana, 1; Legionella pneumophila, 1;
      Mycoplasma pneumoniae, 4; influenza virus, 1), viral culture of throat swabs
      (enterovirus, 8 cases; and adenovirus, 1), high-level antinuclear antibodies
      (>1/400, 3 cases), and thyroid-stimulating hormone (15 abnormal results).
      Antibodies to Toxoplasma and cytomegalovirus, enterovirus recovered from rectal
      swabs, and low-level antinuclear antibodies were seen with equal frequency in
      patients and controls. Using our evaluation strategy, the number of pericardial
      effusions classified as idiopathic was less than in other series. Systematic
      testing for Q fever, Mycoplasma pneumoniae, thyroid abnormalities, and
      antinuclear antibodies, accompanied by viral throat cultures, frequently enabled
      us to diagnose diseases not initially suspected in patients with pericardial
      effusion.

PMID- 14663289
TI  - Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases.
AB  - The centrilobular liver cell necrosis observed in hypoxic hepatitis is generally
      attributed to failure of hepatic blood perfusion. Accordingly, this injury of the
      liver is commonly recognized under the terms "shock liver" or "ischemic
      hepatitis." During a 10-year period, 142 episodes of hypoxic hepatitis were
      consecutively identified in the intensive care unit of a general hospital, and
      the clinical, biological, and hemodynamic parameters were prospectively collected
      on individual files. We conducted the current study to assess retrospectively the
      role of the hemodynamic mechanisms of tissue hypoxia: ischemia, passive venous
      congestion, and hypoxemia. Among the 142 episodes of hypoxic hepatitis, 138 were
      separated in 4 main groups based on clinical features: decompensated congestive
      heart failure (80 cases), acute cardiac failure (20 cases), exacerbated chronic
      respiratory failure (19 cases), and toxic/septic shock (19 cases). An elementary
      hemodynamic evaluation, including blood pressure, central venous pressure, and
      arterial blood gas analysis, was carried out in every episode and a more complete
      hemodynamic assessment through pulmonary artery catheterization was performed in
      61 episodes. The hemodynamic mechanisms responsible for hypoxic hepatitis were
      different in the 4 groups. In congestive heart failure and acute heart failure,
      the hypoxia of the liver resulted from decreased hepatic blood flow (ischemia)
      due to left-sided heart failure and from venous congestion secondary to right
      sided heart failure. In chronic respiratory failure, liver hypoxia was mainly due
      to profound hypoxemia. In toxic/septic shock, oxygen delivery to the liver was
      not decreased but oxygen needs were increased, while the liver was unable to use
      oxygen properly. In all conditions underlying hypoxic hepatitis, except
      toxic/septic shock, a shock state was observed in only about 50% of the cases.
      Therefore, the expressions "shock liver" or "ischemic hepatitis" are misleading
      and should be replaced by the more general term "hypoxic hepatitis."

PMID- 14663290
TI  - Increased prevalence of severe subclinical atherosclerotic findings in long-term
      treated rheumatoid arthritis patients without clinically evident atherosclerotic
      disease.
AB  - We conducted the current study to search for subclinical atherosclerosis in
      patients with rheumatoid arthritis (RA) without clinically evident
      atherosclerosis or its complications who had been treated for a long duration,
      and to assess whether demographic or clinical factors affect the development of
      atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American
      College of Rheumatology classification criteria for RA were recruited from
      Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated
      for at least 5 years, including current treatment with 1 or more disease
      modifying antirheumatic drugs. Patients with diabetes mellitus, renal
      insufficiency, hypertension, cardiovascular or cerebrovascular disease, and
      smokers were excluded. Forty-seven matched controls were also studied. Carotid
      intima-media wall thickness (IMT) and carotid plaques were measured in the right
      common carotid artery. The study was performed using high-resolution B-mode
      ultrasound. Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did
      controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid
      plaques compared with only 7 (15%) controls (p = 0.031). There was a positive
      correlation between the age at the time of study and the carotid IMT. Patients
      with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm)
      than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients
      with carotid plaques had a significantly longer disease duration (mean, 21.0 yr)
      and more extraarticular manifestations (63%) than those without plaques (mean,
      12.7 yr and 26%, respectively). Age at the time of the study and disease duration
      were the best predictive factors for the development of severe morphologic
      expression of atherosclerotic disease. The present study confirms an increased
      frequency of severe subclinical atherosclerotic findings in long-term actively
      treated RA patients from northwest Spain.

PMID- 14663291
TI  - Assessing the validity of a model to identify patients for lymph node biopsy.
AB  - A model to identify adult patients with malignant or granulomatous
      lymphadenopathy demonstrated a sensitivity/specificity of 0.97/0.91 in the
      reference sample by Vassilakopoulos and Pangalis. The current study tests the
      performance of the model in a new sample (n = 151) of patients with peripheral
      lymphadenopathy. Patient charts were reviewed for the biopsy diagnosis and for
      the 6 variables in the model (age, tenderness, size, generalized pruritus,
      supraclavicular lymphadenopathy, and texture). The prevalence rate of malignancy
      or granuloma in the validation sample was 0.26. When the cutoff point of 1 was
      used, as in the original description, the model's sensitivity/specificity in the
      validation sample was 0.97/0.56. The area under the receiver operating
      characteristic curve was 0.89 (95% confidence interval, 0.83-0.95), which was
      still statistically significant discrimination. Since the same model performs
      relatively poorly for the validation sample in terms of low specificity, a more
      accurate prediction model with better specificity would be needed in our patient
      population to help physicians identify those patients with peripheral
      lymphadenopathy who should undergo biopsy.

PMID- 14663292
TI  - Physical activity in primary and secondary prevention - there is a treatment gap.

PMID- 14663293
TI  - Physical activity for primary and secondary prevention. Position paper of the
      Working Group on Cardiac Rehabilitation and Exercise Physiology of the European
      Society of Cardiology.
AB  - There is now clear scientific evidence linking regular aerobic physical activity
      to a significant cardiovascular risk reduction, and a sedentary lifestyle is
      currently considered one of the five major risk factors for cardiovascular
      disease. In the European Union, available data seem to indicate that less than
      50% of the citizens are involved in regular aerobic leisure-time and/or
      occupational physical activity, and that the observed increasing prevalence of
      obesity is associated with a sedentary lifestyle. It seems reasonable therefore
      to provide institutions, health services, and individuals with information able
      to implement effective strategies for the adoption of a physically active
      lifestyle and for helping people to effectively incorporate physical activity
      into their daily life both in the primary and the secondary prevention settings.
      This paper summarizes the available scientific evidence dealing with the
      relationship between physical activity and cardiovascular health in primary and
      secondary prevention, and focuses on the preventive effects of aerobic physical
      activity, whose health benefits have been extensively documented.

PMID- 14663294
TI  - Using waist circumference as a screening tool to identify Colombian subjects at
      cardiovascular risk.
AB  - OBJECTIVE: A cut-off value for waist circumference (WC) of 94 cm associated with
      cardiovascular risk factors (CVRF) has been recommended in Caucasian populations.
      However, it is unclear if recommendations derived from Western studies should be
      extrapolated to populations from developing countries. The present study
      evaluated a group of Colombian subjects to determine and evaluate the level of WC
      capable of identifying subjects with CVRF. RESEARCH DESIGN AND METHODS: (Study 1)
      A cross-sectional study in 145 healthy men, to determine the level of WC
      associated with the following lipid profile (triglycerides 2.25 mmol/L and total
      cholesterol/HDL-cholesterol ratio >5) was performed. (Study 2) Two hundred and
      thirty-eight unrelated male adults were recruited to test whether the new WC cut
      off point would identify subjects with CVRF. RESULTS: (Study 1) A WC cut-off
      point of 88 cm identified subjects with the pre-established lipid profile with a
      sensitivity of 80.6% and specificity of 80.1%, while the WC of 94 cm had a low
      sensitivity (48.3%) and a high specificity (93.3%). Additionally, the values of C
      reactive protein, fasting glucose and insulin levels in subjects with a WC 88 cm
      were significantly higher compared to subjects with WC <88 cm. (Study 2) The
      diagnostic accuracy of the new WC cut-off point (88 cm) to identify subjects with
      two or more CVRF remained acceptable in the new sample studied (sensitivity:
      83.7% and specificity: 84.8%); while the WC value of 94 cm suggested in
      Caucasians showed a very low sensitivity (43.2%) and a high specificity (93.9%).
      CONCLUSIONS: This study demonstrates a higher prevalence of CVRF in our
      population at lower levels of WC than those suggested previously in Caucasians,
      suggesting that ethnic background should be taken into account when using WC as a
      screener for CVRF.

PMID- 14663295
TI  - Exercise training in patients with severe chronic heart failure: impact on left
      ventricular performance and cardiac size. A retrospective analysis of the Leipzig
      Heart Failure Training Trial.
AB  - BACKGROUND: Exercise training (ET) has been shown to improve functional work
      capacity in patients with stable chronic heart failure (CHF) having moderate
      symptoms (NYHA class II). This analysis was conducted, to evaluate the effects of
      ET on left ventricular function and haemodynamics in patients with advanced CHF
      (NYHA class III) fulfilling the inclusion criteria of the COPERNICUS trial.
      METHODS: Seventy-three patients with moderate and advanced CHF were prospectively
      randomised to a training (n=36), or to a control group (n=37). At baseline and
      after six months, patients underwent echocardiography and symptom-limited
      ergospirometry with measurement of central haemodynamics by thermodilution.
      RESULTS: Nine out of 37 patients in the control group (C) and 10 out of 36
      patients in the training group (T) had symptoms of advanced CHF. Exercise
      training over a period of six months resulted in an improvement of functional
      status on average by one NYHA class in patients with advanced CHF. Moreover,
      oxygen uptake at the ventilatory threshold increased by 49% (from 7.7+/-1.0 to
      11.4+/-0.4 mL/min/kg, P<0.01 versus baseline) and at peak exercise by 32% (from
      16.3+/-1.6 to 21.5+/-1.2 mL/min/kg, P<0.01 versus baseline) in training patients.
      The small, but significant reduction in left ventricular end-diastolic diameter
      by 7% (from 70+/-2 to 66+/-2 mm; P<0.05 versus baseline) was accompanied by an
      augmentation in stroke volume at rest by 32% (from 45+/-3 to 60+/-6 mL, P<0.05
      versus baseline) and at peak exercise by 27% (63+/-9 to 81+/-9 mL, P<0.05 versus
      baseline) as a result of ET in patients with advanced CHF. CONCLUSIONS: In
      patients with advanced CHF (NYHA class III), long-term exercise training is
      associated with an enhanced physical work capacity, an improvement in stroke
      volume and a reduction in cardiomegaly.

PMID- 14663296
TI  - Relationship of perceived job stress to total coronary risk in a cohort of
      working men and women in Belgium.
AB  - OBJECTIVE: To examine the relationships of job strain and iso-strain psychosocial
      work environment exposures to 'total coronary risk' (TCR) in a cohort of male and
      female workers in Belgium. METHODS: The sample consists of 15,079 men and 4639
      women aged 35-59 years employed in a wide range of occupations and free of any
      self-reported personal history of CHD. Karasek's job strain model was used to
      define high strain (high demands and low control), low strain, active and passive
      jobs. Iso-strain was defined as the combination of a high strain job with low
      worksite social support, and is compared to the other combinations. Total
      coronary risk is a composite measure based on a Framingham function assessing the
      risk of developing coronary heart disease (CHD) within the next 10 years; high
      and low levels of TCR were defined. Logistic regressions in each gender were
      applied to explore relationships, adjusting for age, level of education,
      occupational class and sector of employment. RESULTS: In male workers, the age
      adjusted prevalence of high TCR is highest in (1) in the lowest quartile group of
      job control and (2) in the 'high strain' group. The multivariate logistic
      regressions comparing high strain, active and passive work exposures to low
      strain work did not indicate a significant association with high TCR. Likewise,
      iso-strain jobs were neither found to be associated with high TCR. CONCLUSION:
      Our cross-sectional analysis provides no support for the hypothesis that the
      psychosocial work environment is strongly associated with the TCR estimate in
      healthy workers.

PMID- 14663297
TI  - Effects of chronic alcohol consumption on lipid levels, inflammatory and
      haemostatic factors in the general population: the 'ATTICA' Study.
AB  - BACKGROUND: Epidemiological studies suggest an unclear effect of alcohol
      consumption on cardiovascular risk. This ambiguity is likely related to the
      quantity of alcohol consumed in populations studied. The aim of this work was to
      evaluate the association between chronic alcohol consumption and several clinical
      and biochemical parameters related to coronary risk, in cardiovascular disease
      free men and women. METHODS: The 'ATTICA' study is a population-based cohort,
      which randomly enrolled 750 men and 883 women (18-88 years old) from area around
      Athens, during 2001-2002. We investigated the association between alcohol
      consumption and arterial blood pressure, fibrinogen levels, glucose
      concentration, total cholesterol, HDL and LDL, apolipoprotein A1 and B, Lp(a),
      uric acid, leucocyte count, triglycerides, C-reactive protein and homocysteine
      levels. RESULTS: Multivariate analysis, after controlling for several potential
      confounders, revealed a J-shaped association between alcohol intake (none, 1-2, 3
      4, 5+ wine glasses/day) and uric acid, C-reactive protein, homocysteine,
      fibrinogen, triglycerides, apolipoproteins A1 and B, HDL and total cholesterols,
      blood glucose levels, leucocyte count and arterial blood pressure levels (only in
      males). The most beneficial values of all these biochemical and clinical
      parameters were found in alcohol intake of 100-200 ml (12% alcohol), even after
      adjustment for various potential confounders. CONCLUSIONS: The controversial
      association between alcohol intake and cardiovascular disease seems to be
      partially explained by the J-shaped relation of several biochemical parameters
      related to atherosclerosis and the amount of alcoholic beverages consumed.

PMID- 14663298
TI  - Plasma lipoprotein Lp(a), markers of haemostasis and inflammation, and risk and
      severity of coronary heart disease.
AB  - BACKGROUND: Elevated plasma (Lp(a)) levels may represent an independent risk
      factor for atherothrombotic complications but the relation between Lp(a) levels
      and the extent of coronary artery disease (CHD) has been discussed
      controversially. Little is known about potential atherothrombogenic mechanisms of
      Lp(a). DESIGN: Case-control study. METHODS: We assessed the relationship between
      plasma Lp(a) and angiographically defined CHD, evaluating the severity of
      coronary atherosclerosis by three different scores. A total of 312 patients with
      stable angina aged 40-68 years with at least one coronary stenosis > 50% were
      studied. A group of 479 voluntary blood donors matched for age and sex served as
      controls. A complete lipid profile and a large number of markers of coagulation,
      fibrinolysis and inflammation were measured. RESULTS: Plasma levels of Lp(a) were
      significantly higher in patients (14.8 mg/dl; 5.4-47.1 mg/dl;
      median/interquartile range) than in controls (9.7 mg/dl; 3.5-25.3) (P<0.0001). In
      a logistic regression model, the fully adjusted Odds Ratio for CHD was 3.3 (95%
      confidence interval (CI) 1.8-5.6, P<0.0001) for patients in the upper quartile of
      the Lp(a) distribution compared to the bottom quartile. There was no appreciable
      association between Lp(a) and apolipoproteins, markers of haemostasis,
      fibrinolysis and inflammation and the severity of CHD. CONCLUSIONS: These results
      indicate that elevated plasma Lp(a) levels may be an independent risk factor for
      CHD but unrelated to the severity and extension of CHD. Furthermore, there is no
      good evidence that the presumed link between Lp(a) and CHD is mediated by
      increased levels of markers of inflammation, or interference with markers of
      fibrinolysis or coagulation.

PMID- 14663299
TI  - Energy expenditure in wheelchair racing and handbiking - a basis for prevention
      of cardiovascular diseases in those with disabilities.
AB  - OBJECTIVE: Handbiking and wheelchair racing have gained increased popularity in
      Germany. This is important because of the inability of wheelchair-dependent
      people to maintain cardiovascular health and fitness through daily activities.
      The purpose of this study was to evaluate the energy expenditure (EE; kcal/h) of
      wheelchair-dependent individuals. METHODS: Ten wheelchair racers (WR) and 17
      handbikers (HB) completed a basal metabolism evaluation, an incremental exercise
      test until exhaustion and an endurance test. Oxygen uptake and carbon dioxide
      production ([V(. -)]O(2), [V(. -)]CO(2); ml/min), arterialized capillary blood
      lactate concentration (LA; mmol/l) and heart rate (HR; bpm) were recorded during
      each test. EE was calculated by indirect calorimetry. RESULTS: In the endurance
      test [V(. -)]O(2), [V(. -)]CO(2), LA, HR and EE at an intensity corresponding to
      2 mmol/l lactate were: HB: 1332+/-368 ml/min, 1178+/-303 ml/min, 2.23+/-0.85
      mmol/l, 116.8+/-19.1 bpm, 389.6+/-105.4 kcal/h; WR:1175+/-285 ml/min, 1145+/-258
      ml/min, 2.65+/-0.36 mmol/l, 142.5+/-28.0 bpm, 341.7+/-84.0 kcal/h. At an
      intensity corresponding to 4 mmol/l lactate the values were: HB: 1792+/-408
      ml/min, 1666+/-326 ml/min, 4.27+/-1.40 mmol/l 146.1+/-22.8 bpm, 530.1+/- 115.4
      kcal/h; WR: 1505+/-210 ml/min, 1427+/-188 ml/min, 3.31+/-1.0 mmol/l, 165.3+/-22.7
      bpm, 445.5+/-70.8 kcal/h. CONCLUSION: The results show that EE of HB and WR is
      high enough to maintain fitness and probably to help to prevent cardiovascular
      diseases even at a moderate intensity.

PMID- 14663300
TI  - A randomized non-pharmacological intervention study for prevention of ischaemic
      heart disease: baseline results Inter99.
AB  - BACKGROUND: Various strategies have been used to induce lifestyle changes to
      reduce ischaemic heart disease (IHD) with various successes. The aim of Inter99
      is to assess the effect on IHD incidence of individually tailored non
      pharmacological intervention on lifestyle using a newly developed computer-based
      health educational tool. The article describes the study and baseline results.
      METHODS: From a population of 61,301 individuals two random samples (high
      intensity intervention group (A), n = 11,708; low intensity intervention group
      (B), n = 1308) are screened to assess their absolute risk of IHD. Those at high
      risk receive individual lifestyle counselling. Individuals in group A are
      furthermore offered lifestyle counselling in groups on smoking cessation or
      physical activity/diet over a 6-month period. Individuals in group B are referred
      to their GP. High-risk persons are re-counselled after 1 and 3 years and the
      whole group is re-invited after 5 years. The remaining 48,285 (group C) are
      followed by questionnaire. The total population is followed through central
      registers. Intermediate end-points are changes in lifestyle, cholesterol, blood
      pressure and body mass index. Final end-point is reduction in incidence of IHD.
      RESULTS: The randomization leads to comparable groups. Participation rate was
      52.5%. A total of 60% fulfilled the predetermined criteria for being at high risk
      for developing IHD. After an individual lifestyle counselling 41% accepted group
      based counselling. CONCLUSION: This large randomized population based trial
      discloses a noticeable need for and acceptance of lifestyle intervention in the
      general population.

PMID- 14663301
TI  - Promoting physical activity in a multi-ethnic district - methods and baseline
      results of a pseudo-experimental intervention study.
AB  - BACKGROUND AND DESIGN: A combined community and high-risk intervention study of
      three years duration started in one district in Oslo after a baseline health
      survey in two multi-ethnic and low socio-economic status (SES) districts, using a
      pseudo-experimental design with an age-matched sample from the other district as
      controls. The intervention focused on promoting physical activity to reduce the
      burden of type 2 diabetes and cardiovascular disease (CVD). METHODS: A total of
      6140 subjects were invited to participate (age group: 31-67). Data on health
      status and health-related behaviours, collected via standardized questionnaires,
      physical examinations and blood sample analyses, were available for 2950 persons
      (attendance rate 48%), whereas official statistics were available for the invited
      population. RESULTS: The prevalence of self-reported diabetes was 5.1% in men and
      3.5% in women, but the total diabetes prevalence was 9% for men and 5.1% for
      women. One-third of the population were sedentary in their leisure time, men more
      than women (38% versus 29%). The prevalence of obesity did not differ between the
      genders (21% had BMI 30 kg/m(2)). The relatively high mean scores on most
      psychosocial variables related to physical activity, especially among women,
      indicate a high motivational readiness for increase in physical activity
      behaviour. The baseline data, for example on the prevalence of chronic diseases
      were similar in the two districts. CONCLUSION: The prevalence of self-reported
      diabetes is remarkably higher than reported from other studies in Norway. The
      proportion of undiagnosed diabetes was higher than anticipated, and constituted
      39% of all those categorized as diabetics.

PMID- 14663302
TI  - Does early immunotherapy reduce the conversion of ocular myasthenia gravis to
      generalized myasthenia gravis?

PMID- 14663303
TI  - Immunotherapy of ocular myasthenia gravis reduces conversion to generalized
      myasthenia gravis.
AB  - BACKGROUND: Several retrospective studies have suggested that immunotherapy,
      including prednisolone, azathioprine and thymectomy, reduces progression of
      ocular myasthenia gravis to generalized myasthenia gravis. This study examines
      the effect of immunotherapy on generalization rates in ocular myasthenia patients
      who are acetylcholine receptor (AChR) antibody-positive. METHODS: Retrospective
      record review of 34 patients from three university-based hospitals with neurology
      and neuro-ophthalmology services in Australia. In all patients, positive AChR
      antibodies were recorded, the initial symptoms were purely ocular, and all had at
      least 2 years of follow-up. The patients who developed generalized myasthenia
      gravis were compared with those who remained purely ocular. RESULTS: There were
      21 patients who developed generalized myasthenia gravis. Of these 21, only 2
      (9.5%) had received prior immunotherapy. Among the 13 patients whose symptoms
      remained purely ocular, 10 (76.9%) had received prior immunotherapy. CONCLUSIONS:
      In this study, most of the patients who progressed from ocular myasthenia to
      generalized myasthenia had not received prior immunotherapy. This study adds
      weight to the call for a prospective trial of early immunotherapy in patients
      with ocular myasthenia.

PMID- 14663304
TI  - Interferon-alpha-associated bilateral simultaneous ischemic optic neuropathy.
AB  - The authors describe one patient with essential thrombocytosis and one with
      chronic hepatitis C infection who developed bilateral simultaneous anterior
      ischemic optic neuropathy within 3 months of starting treatment with interferon
      alpha. One patient had several typical risk factors for conventional AION; the
      other did not. These cases are the fourth and fifth reported examples of this
      phenomenon. Interferon-alpha treatment may cause or aggravate the risk of
      developing anterior ischemic optic neuropathy. Vulnerable patients should be
      advised of this potential complication, assisted in reducing risk factors, and
      monitored for optic nerve and retinal vascular complications.

PMID- 14663305
TI  - Laser pointer visual field screening.
AB  - BACKGROUND: Sensitivity of confrontation visual field (CVF) screening is low
      unless defects are significant. We compared the sensitivity of laser pointer
      visual field screening (LVF) with conventional CVF for identifying eyes with
      abnormal automated perimetry. METHODS: Ninety consecutive patients presenting for
      HVF prospectively underwent a masked comparison of CVF and LVF testing (175 eyes)
      from April to May 2000. LVF was performed using a laser pointer target projected
      onto a tangent screen. Points were tested in random fashion on either side of the
      vertical and horizontal meridians, near central fixation, around the blind spot,
      and in each quadrant. Single and double simultaneous finger counting was used to
      test CVF. RESULTS: LVF demonstrated significantly greater sensitivity as compared
      with CVF (73% versus 31%, P = 0.001) in identifying field defects found on HVF.
      Specificities for LVF and CVF were 82% and 99%, respectively. The average testing
      times per eye were 0.5 minute for CVF, 1.5 minutes for LVF, and 8.0 minutes for
      HVF. CONCLUSIONS: In this cohort, laser visual field testing was significantly
      more sensitive than confrontation testing. It may represent an effective, time
      efficient tool for visual field screening.

PMID- 14663306
TI  - Posner-Schlossman syndrome and nonarteritic anterior ischemic optic neuropathy.
AB  - A 41-year-old woman with acute OD pain and decreased visual acuity presented with
      anterior uveitis, an intraocular pressure of 56 mm Hg, an open angle, ipsilateral
      nerve fiber bundle visual field defects, and optic nerve edema. With control of
      intraocular pressure and uveitis, visual acuity improved to 20/25, visual field
      defects persisted, and optic disc pallor developed. She has remained stable over
      23 months of follow-up. This case represents a concurrence of glaucomatocyclitic
      crisis (Posner-Schlossman syndrome, PSS) and nonarteritic ischemic optic
      neuropathy (NAION). Although this combination occurs rarely, patients with PSS
      and other risk factors for NAION, including an optic disc that lacks a
      physiologic cup, should be protected against NAION by prophylactic treatment with
      ocular antihypertensive medications.

PMID- 14663308
TI  - Siegrist streaks in giant cell arteritis.
AB  - A patient who presented with symptoms of giant cell arteritis was found to have a
      right ophthalmic artery occlusion. One month after initial evaluation, the
      peripheral retina demonstrated multiple linear bands of chorioretinal atrophy
      known as Siegrist streaks. Although most commonly described in the setting of
      acute hypertension, Siegrist streaks also occur in patients with giant cell
      arteritis.

PMID- 14663307
TI  - Solitary intracranial extra-osseous plasmacytoma presenting with ophthalmic
      signs.
AB  - Solitary plasmacytomas rarely develop in the skull, meninges, or brain.
      Ophthalmic signs as the initial manifestations of solitary intracranial
      plasmacytoma have rarely been described. We report the neuro-ophthalmologic,
      imaging, and pathologic findings for two patients. One patient presented with
      optic neuropathy, the second with bilateral sixth nerve palsies. Plasmacytoma is
      a treatable intracranial tumor that should be considered in the differential
      diagnosis of patients who present with optic neuropathy or sixth nerve palsy.

PMID- 14663309
TI  - Retinal vascular abnormalities in neurofibromatosis type 1.
AB  - Microvascular retinal abnormalities, presenting in a corkscrew configuration,
      have been very recently described in patients with neurofibromatosis type 1 (NF
      1). We report one more patient with NF-1 who had distinctive corkscrew retinal
      vessels superior and inferior to the fovea. This patient further supports the
      existence of a true association between this recently described retinal finding
      and NF-1.

PMID- 14663310
TI  - Rocky Mountain Spotted Fever as a cause of macular star figure.
AB  - An 86-year-old woman with a history of tick bites in the previous months
      developed subnormal visual acuity in both eyes, keratic precipitates, anterior
      chamber and vitreous cells, optic disc edema, retinal hemorrhages, and retinal
      arteriolar sheathing. She had no fever or skin rash. Three weeks later, binocular
      macular star figures appeared. Brain imaging was negative; cerebrospinal fluid
      disclosed a lymphocytic pleocytosis and elevated protein. The serum Rickettsia
      rickettsii antibody test was markedly positive, establishing a diagnosis of Rocky
      Mountain Spotted Fever (RMSF) as the cause of the ophthalmic findings. Despite
      treatment with oral doxycycline, these findings improved only modestly. Although
      neuroretinitis has been previously described in RMSF, macular star has not been
      documented.

PMID- 14663311
TI  - The multifocal visual evoked potential.
AB  - With the multifocal technique, visual evoked potentials (VEPs) can be recorded
      simultaneously from many regions of the visual field. For the multifocal VEP
      (mfVEP), the patient views a display that typically contains 60 sectors, each
      with a checkerboard pattern. The display covers about the same retinal area as
      the 24-2 Humphrey visual field (HVF). However, due to the scaling of the sectors
      of the mfVEP display, the fields are sampled differently by the mfVEP and HVF. To
      assess local defects in the visual field, the mfVEP responses must be compared
      with normal controls. These comparisons require relatively sophisticated analyses
      and software. Whereas the mfVEP can be recorded relatively easily with the same
      equipment used to record multifocal electroretinograms (mfERGs), the software
      needed to perform the analysis is not yet widely available. The mfVEP is valuable
      for ruling out non-organic visual loss, diagnosing and following patients with
      optic neuritis/multiple sclerosis, evaluating patients with unreliable or
      questionable HVFs, and following disease progression. When combined with the
      mfERG, diseases of the outer retina (before the retinal ganglion cells) can be
      distinguished from diseases of the ganglion cells and/or optic nerve. The
      difficulties encountered in recording and analyzing mfVEP responses are greater
      than those involved in full-field VEP testing. Thus, in its current form, the
      mfVEP is best recorded and interpreted by ophthalmologists and
      electrophysiologists experienced with the technique. However, this technique is
      developing rapidly; advances in commercial hardware and software are expected in
      the near future.

PMID- 14663312
TI  - Adelbert Ames and the Dartmouth Eye Institute.

PMID- 14663313
TI  - Annual meeting of the Association for Research in Vision and Ophthalmology
      (ARVO), Fort Lauderdale, Florida, May 4-9, 2003.

PMID- 14663314
TI  - The 6th European Neuro-Ophthalmological Society (EUNOS) meeting, Goteborg,
      Sweden, June 15-18, 2003.

PMID- 14663315
TI  - Enhanced scintigraphic protocol required for optimal preoperative localization
      before targeted minimally invasive parathyroidectomy.
AB  - At our tertiary care institution, a targeted minimally invasive parathyroidectomy
      (MIP) is the preferred surgical procedure for primary hyperparathyroidism.
      Similar to unilateral neck exploration (UNE), preoperative scintigraphic
      localization of the adenoma in relation to the midline is required. However, in
      contrast to the abbreviated standard incision for UNE, 2 distinct incision sites,
      1 medial and 1 lateral, are available on each side with MIP. The incision site is
      ultimately chosen based on scintigraphic determination of the adenoma's vascular
      origin to facilitate ligation and removal. Unfortunately, the scintigraphic
      location of a parathyroid adenoma does not necessarily reflect the site of its
      vascular origin. We reviewed our database to identify factors that accurately
      predict the site of vascular origin of parathyroid adenomas. A retrospective
      chart review was performed on 125 patients who underwent Tc-99m sestamibi
      scintigraphy and parathyroidectomy. Scintigraphic localization, surgical
      findings, and histopathology were recorded. Preoperative image interpretations
      that were discordant with operative findings were independently reviewed.
      Scintigraphy identified the presence of an adenoma in 105 of 118 patients (89%)
      with primary hyperparathyroidism. In 17 of the 105 cases (16%), the scintigraphic
      interpretation did not accurately reflect the site of superior or inferior
      vascular origin seen at surgery. In many discordant cases, anterior images were
      insufficient for determining the vascular origin. The posterior displacement of
      an adenoma in relation to the thyroid on early lateral images was often critical
      in determining the superior or inferior vascular origin. Scintigraphic
      determination of the superior or inferior vascular origin of a parathyroid
      adenoma directs incision placement for MIP. Imaging protocols should include
      early lateral images when localizing parathyroid adenomas before minimally
      invasive parathyroidectomy.

PMID- 14663317
TI  - High predictive value of F-18 FDG PET patterns of the spine for metastases or
      benign lesions with good agreement between readers.
AB  - Two nuclear medicine physicians retrospectively evaluated fluorine-18
      fluorodeoxyglucose (FDG) positron emission tomography (PET) spine abnormalities
      in patients with cancer with the purpose of identifying straightforward criteria
      for benign versus malignant spine abnormalities. Four hundred seventy-five
      consecutive patients with colon, breast, and lung cancer were evaluated with FDG.
      Thirty-two patients (32) had spine abnormalities, 30 of 32 patients had adequate
      follow up for a final diagnosis, and 29 of 30 patients' studies were available to
      both PET readers for this retrospective review. The readers categorized the FDG
      PET abnormalities as benign, metastatic, or equivocal using a straightforward set
      of criteria. A final diagnosis was made using magnetic resonance imaging (MRI),
      computed tomography (CT), plain films, bone scans, previous studies, and clinical
      follow up. A single spinal focus of increased FDG activity had a relatively high
      probability of being a spinal metastasis (71%); and the more foci, the higher the
      probability. Segmental decreased activity of the spine after radiation therapy
      indicated benignity. The only discrepancies were with 3 abnormalities, each
      called metastasis by 1 reader and equivocal by the other, with a final diagnosis
      of metastasis in each case. Equivocal patterns required CT or MR correlation,
      because these could be either malignant or benign. However, abnormal patterns
      fulfilling either the benign or metastatic criteria described here resulted in
      the correct diagnoses of benign spinal changes or spinal metastases,
      respectively, in 100% of cases with low interobserver variation. No study was
      interpreted as benign by 1 reader and metastasis by the other. The 2 nuclear
      medicine readers agreed in their interpretations in 90% of cases.

PMID- 14663316
TI  - The role of fluorine-18 deoxyglucose positron emission tomography in the
      management of patients with metastatic melanoma: impact on surgical decision
      making.
AB  - Malignant melanoma can metastasize to almost any organ site. Optimal management
      requires sensitive radiographic evaluation of the entire body. The optimal
      management of patients with metastatic melanoma requires accurate assessment of
      extent of disease (EOD). The objective of this study was to evaluate the accuracy
      of fluorine-18 deoxyglucose (FDG) whole-body positron emission tomography (PET)
      in determination of EOD in patients with metastatic melanoma and its impact on
      surgical and medical management decisions. Forty-nine patients (30 men, 19 women;
      aged 25-83 years) with known or suspected metastatic melanoma underwent EOD
      evaluation using computerized tomography (CT) of the chest, abdomen, and pelvis,
      and magnetic resonance imaging (MRI) of the brain. After formulation of an
      initial treatment plan, the patients underwent FDG-PET imaging. The EOD
      determined by PET was compared with physical examination and conventional
      radiography findings. Fifty-one lesions were pathologically evaluated. The impact
      of PET on patient management was assessed based on the alterations made in the
      initial treatment plan after reevaluation of the patients using the information
      obtained by PET. The PET scan identified more metastatic sites in 27 of 49 (55%)
      of the patients who had undergone a complete set of imaging studies, including CT
      scans of the chest, abdomen, and pelvis, and MRI of the brain. In 6 of those 27
      patients, PET detected disease outside the fields of CT and MRI. Fifty-one
      lesions were resected surgically. Of these, 44 were pathologically confirmed to
      be melanoma. All lesions larger than 1 cm (29 of 29) were positive on PET,
      whereas only 2 of 15 (13%) lesions smaller than 1 cm were detected by PET. The
      results of PET led treatment changes in 24 patients (49%). Eighteen of these
      changes (75%) were surgical. In 12 cases (67%), the planned operative procedure
      was cancelled, and in 6 cases (33%), an additional operation(s) was performed. In
      6 of 24 (25%) patients, biochemotherapy, radiation therapy, or an experimental
      immunotherapy protocol was prompted by identification of new foci of disease.
      Compared with conventional imaging, FDG-PET provides more accurate assessment of
      EOD in patients with metastatic melanoma. Significant surgical and medical
      treatment alterations were made based on PET results.

PMID- 14663318
TI  - Tc-99m exametazime-labeled leukocyte scans in the study of infections in skull
      neurosurgery.
AB  - Diagnosis and follow-up of skull infections are usually performed by neurologic
      examination, laboratory tests and instrumental diagnostic methods such as
      computed tomography (CT) and magnetic resonance imaging (MRI). These have,
      however, shown some limitations for specificity. The aim of the current study was
      to evaluate the overall contribution of Tc-99m exametazime-labeled leukocyte
      imaging scan Tc-99m hexamethylpropyleneamine (HMPAO) labeled white blood cells
      (WBC) in the diagnosis and management of infections in skull neurosurgery. Thirty
      four patients were subdivided into 4 groups on the basis of the suspected
      pathology: intracerebral lesions on CT or MRI (group A, n = 20), suspected
      postsurgical infections (group B, n = 6), suspected deep infection of the
      surgical wound (group C, n = 4), and suspected infection of the
      ventriculoperitoneal shunt (group D, n = 4). All patients underwent CT, MRI, and
      Tc-99m HMPAO WBC imaging. Patients in group C also underwent bacteriologic and
      culture examinations of wound secretions if present. In positive cases in group
      A, Tc-99m HMPAO WBC imaging was repeated. The scintigraphic results were compared
      with histologic findings in patients who underwent surgery and with the results
      of a 12-month clinical follow-up in the remaining patients. Tc-99m HMPAO WBC
      scans correctly detected the infections in all groups. Furthermore, such imaging
      proved to be able to document recovery from the disease in all of the assessed
      cerebral abscesses. This study may have an important role both in the diagnosis
      and in the management of infections in skull neurosurgery, which, it is hoped,
      will be confirmed in the future.

PMID- 14663319
TI  - Intense fluorodeoxyglucose activity in pulmonary amyloid lesions on positron
      emission tomography.

PMID- 14663320
TI  - Biliary leak with normal gallbladder appearance on cholescintigraphy.

PMID- 14663321
TI  - Fluorodeoxyglucose positron emission tomography in the presence of cardiac
      metastases.

PMID- 14663322
TI  - Tc-99m-labeled monoclonal antibody fragment imaging in a patient with Fever of
      unknown origin.

PMID- 14663323
TI  - Detection of parathyroid hyperplasia, lymph node metastasis from thyroid cancer,
      and thyroid adenomatous hyperplasia using Tc-99m MIBI.

PMID- 14663324
TI  - Radionuclide detection of peritoneovenous shunt patency.

PMID- 14663325
TI  - Neonatal gynecomastia visualized during Tc-99m pertechnetate thyroid
      scintigraphy.

PMID- 14663326
TI  - Hypertrophic osteitis of the clavicle.

PMID- 14663327
TI  - Hemibody uptake on bone scintigraphy in polyostotic fibrous dysplasia.

PMID- 14663328
TI  - Chronic hypersensitivity pneumonitis with heart involvement observed during in
      111 DTPA octreotide (OctreoScan) imaging.

PMID- 14663329
TI  - Angiolymphoid hyperplasia with eosinophilia: F-18 FDG PET and MR demonstration.

PMID- 14663330
TI  - Gallium-67 citrate imaging before and after treatment of acute Q fever.

PMID- 14663331
TI  - Extraosseous skin and subcutaneous tissue uptake of Tc-99m HMDP in a surgical
      scar after laparotomy.

PMID- 14663334
TI  - Magnetic resonance imaging in experimental models of brain disorders.
AB  - This review gives an overview of the application of magnetic resonance imaging
      (MRI) in experimental models of brain disorders. MRI is a noninvasive and
      versatile imaging modality that allows longitudinal and three-dimensional
      assessment of tissue morphology, metabolism, physiology, and function. MRI can be
      sensitized to proton density, T1, T2, susceptibility contrast, magnetization
      transfer, diffusion, perfusion, and flow. The combination of different MRI
      approaches (e.g., diffusion-weighted MRI, perfusion MRI, functional MRI, cell
      specific MRI, and molecular MRI) allows in vivo multiparametric assessment of the
      pathophysiology, recovery mechanisms, and treatment strategies in experimental
      models of stroke, brain tumors, multiple sclerosis, neurodegenerative diseases,
      traumatic brain injury, epilepsy, and other brain disorders. This report reviews
      established MRI methods as well as promising developments in MRI research that
      have advanced and continue to improve our understanding of neurologic diseases
      and that are believed to contribute to the development of recovery improving
      strategies.

PMID- 14663335
TI  - Plasmatic level of neuroinflammatory markers predict the extent of diffusion
      weighted image lesions in hyperacute stroke.
AB  - Sixteen patients with acute middle cerebral artery stroke were studied to
      correlate neuroinflammatory markers with perfusion- and diffusion-weighted
      magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less
      than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin
      (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor
      (TNF)-alpha were serially measured (by ELISA), and MRI was performed. In cerebral
      ischemia, tissue destruction seems related to matrix metalloproteinases
      expression because baseline MMP-9 was the only predictor of the infarct volume
      measured as a DWI lesion (lineal regression: b = 0.50, 0.25-0.74; P < 0.001).
      Moreover, the extent of hypoperfused brain area (PWI) was associated with a
      proinflammatory cytokine release in the next hours (TNF-alpha and IL-6).

PMID- 14663336
TI  - Activation systems for latent matrix metalloproteinase-2 are upregulated
      immediately after focal cerebral ischemia.
AB  - During focal cerebral ischemia, matrix metalloproteinase-2 (MMP-2) can contribute
      to the loss of microvessel integrity within ischemic regions by degrading the
      basal lamina. MMP-2 is secreted in latent form (pro-MMP-2), but the activation of
      pro-MMP-2 in the ischemic territory has not been shown. Immunohistochemical and
      in situ hybridization studies of the expression of the direct activators of MMP
      2, MT1-MMP and MT3-MMP, and the indirect activation system tissue plasminogen
      activator, urokinase (u-PA), its receptor (u-PAR), and its inhibitor PAI-1 after
      middle cerebral artery occlusion/reperfusion were undertaken in basal ganglia
      samples from 26 adolescent male baboons. The expressions of all three MMPs, u-PA,
      u-PAR, and PA1-1, but not tissue plasminogen activator, were increased from 1
      hour after middle cerebral artery occlusion in the ischemic core. mRNA
      transcripts confirmed the increases in latent MMP-2, u-PA, u-PAR, and PAI-1
      antigen very early after middle cerebral artery occlusion. The expression
      patterns are consistent with secretion of pro-MMP-2 and its activators in the
      ischemic core, perhaps from separate cell compartments. The rapid and coordinate
      appearance of pro-MMP-2 and its activation apparatus suggest that in the primate
      striatum this protease may participate in matrix injury during focal cerebral
      ischemia.

PMID- 14663337
TI  - Activation of receptor-mediated angiogenesis and signaling pathways after VEGF
      administration in fetal rat CNS explants.
AB  - SUMMARY: The angiogenic role of vascular endothelial growth factor (VEGF)
      receptors, flk-1 and flt-1, and their downstream signaling pathways, MAPK/ERK and
      PI-3 kinase, were examined in a fetal rat cortical explant model after exposure
      to exogenous VEGF. Treatment with VEGF resulted in substantial neovascularization
      characterized by increased vascular flk-1 receptor expression, whereas flt-1
      receptor protein expression was absent. The specific role of flk-1 receptors in
      the angiogenic process was confirmed by the addition of antisense
      oligonucleotides (AS-ODNs) to flk-1, which blocked angiogenesis, whereas AS-ODNs
      to flt-1 had no effect. These results were further supported by the finding that
      specific chemical inhibition of flk-1 receptors caused disruption of the
      angiogenic response, whereas inhibition of the flt-1 receptors had no effect.
      Application of either MAPK/ERK or PI-3 kinase pathway inhibitors disrupted VEGF
      induced angiogenesis, thereby indicating that both signaling pathways mediate
      this process. Thus VEGF binding to the endothelial flk-1 receptor activates the
      MAPK/ERK and PI-3 kinase pathways, resulting in neoangiogenic events. Of interest
      is the fact that although VEGF is regarded as a vascular permeability factor, its
      application to nascent cortical tissue caused an increase in a key physiologic
      protein of the blood-brain barrier function, glucose transporter-1, suggesting
      that the cytokine may have a role in blood-brain barrier development.

PMID- 14663338
TI  - Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic
      brain after occlusion/reperfusion of the middle cerebral artery in rats.
AB  - Matrix metalloproteinase-9 (MMP-9) activity increases in the brain during the
      first day after focal ischemia and might be involved in the pathogenesis of
      tissue damage. We previously showed MMP-9 in the extracellular space of brain
      parenchyma along with neutrophil recruitment after ischemia. In the present
      study, we tested whether neutrophils were a direct source of enhanced MMP-9 in
      the ischemic brain. Neutrophil infiltration was prevented either by injecting an
      antibody against ICAM-1, which abrogates neutrophil adhesion to the endothelial
      vessel wall, or by inducing neutropenia. One-hour intraluminal middle cerebral
      artery occlusion with reperfusion was induced, and studies were performed at 24
      hours. Circulating neutrophils expressed 95-kDa MMP-9 and dimers, and infiltrated
      neutrophils stained positive for MMP-9. The expression of MMP-9 (mainly 95-kDa
      proform and dimers and, to a lesser extent, 88-kDa form) increased in brain after
      ischemia/reperfusion. Treatments preventing neutrophil infiltration failed to
      preclude the ischemia-induced increase in 88-kDa MMP-9 form and gelatinase
      activity in neurons and blood vessels. However, these treatments prevented the
      major increase in 95-kDa MMP-9 form and dimers. We conclude that neutrophil
      infiltration highly contributes to enhanced MMP-9 in the ischemic brain by
      releasing MMP-9 proform, which might participate in the tissular inflammatory
      reaction.

PMID- 14663339
TI  - Determination of kinetic rate constants for 2-[18F]fluoro-2-deoxy-D-glucose and
      partition coefficient of water in conscious macaques and alterations in aging or
      anesthesia examined on parametric images with an anatomic standardization
      technique.
AB  - Kinetic rate constants for 2-[18F]fluoro-2-deoxy-d-glucose (FDG) and the tissue
      blood partition coefficient of water were determined using dynamic positron
      emission tomography in conscious macaques, and alterations in these parameters in
      aging or anesthesia were also examined. The parameters were estimated on a pixel
      by-pixel basis using an anatomic standardization technique; group differences
      were then examined on the parametric images from the young, aged, and anesthesia
      groups. For the conscious condition, seven young and seven aged male rhesus
      macaques were used; six young male rhesus macaques were used for the isoflurane
      anesthesia condition. H2 15O and FDG were used as tracers. The kinetic parameters
      were estimated by a nonlinear least-square fitting procedure with compartment
      models including terms for the cerebral blood volume (CBV) and time delay of the
      input function. Cerebral blood flow (CBF) and cerebral metabolic rate of glucose
      (CMRglc) were also calculated from the estimated parameters. In the aged group,
      glucose phosphorylation was decreased more than glucose transport, and the
      occipital cortex was the most affected region where reduction in CBV, CMRglc, and
      CBF were also observed. In the anesthesia group, glucose transport was decreased;
      however, glucose phosphorylation was not affected except for the occipital pole.
      The occipital cortex was also the most affected region. The tissue-blood
      partition coefficient of water was decreased globally.

PMID- 14663340
TI  - Thrombin preconditioning attenuates brain edema induced by erythrocytes and iron.
AB  - Pretreatment with a low intracerebral dose of thrombin reduces brain edema after
      hemorrhagic and thrombo-embolic stroke. We have termed this phenomena thrombin
      preconditioning (TPC) or thrombin-induced brain tolerance. Red blood cell lysis
      and iron overload contribute to delayed edema formation after intracerebral
      hemorrhage. The present study examined whether TPC can attenuate the brain edema
      induced by lysed red blood cells or iron. It also examined whether TPC is
      associated with increasing hypoxia inducible factor-1alpha (HIF-1alpha) levels
      and alterations in two HIF-1alpha target genes, transferrin (Tf) and transferrin
      receptor (TfR), within the brain. Brain edema was measured by wet/dry weight
      method. HIF-1alpha, Tf, and TfR were measured by Western blot analysis and
      immunohistochemistry. We found that TPC reduces the edema induced by infusion of
      lysed red blood cells and iron. Thrombin increases HIF-1alpha levels through
      p44/42 mitogen activated protein kinases pathway. Thrombin also increases Tf and
      TfR levels in the brain. These results indicate that HIF-1alpha and its target
      genes may be involved in thrombin-induced brain tolerance.

PMID- 14663341
TI  - Quantitative cerebral blood flow measurements in the rat using a beta-probe and
      H2 15O.
AB  - Beta-probes are a relatively new tool for tracer kinetic studies in animals. They
      are highly suited to evaluate new positron emission tomography tracers or measure
      physiologic parameters at rest and after some kind of stimulation or
      intervention. In many of these experiments, the knowledge of CBF is highly
      important. Thus, the purpose of this study was to evaluate the method of CBF
      measurements using a beta-probe and H2 15O. CBF was measured in the barrel cortex
      of eight rats at baseline and after acetazolamide challenge. Trigeminal nerve
      stimulation was additionally performed in five animals. In each category, three
      injections of 250 to 300 MBq H2 15O were performed at 10-minute intervals. Data
      were analyzed using a standard one-tissue compartment model (K1 = CBF, k2 =
      CBF/p, where p is the partition coefficient). Values for K1 were 0.35 +/- 0.09,
      0.58 +/- 0.16, and 0.49 +/- 0.03 mL x min(-1) x mL(-1) at rest, after
      acetazolamide challenge, and during trigeminal nerve stimulation, respectively.
      The corresponding values for k2 were 0.55 +/- 0.12, 0.94 +/- 0.16, and 0.85 +/-
      0.12 min(-7), and for p were 0.64 +/- 0.05, 0.61 +/- 0.07, and 0.59 +/- 0.06. The
      standard deviation of the difference between two successive experiments, a
      measure for the reproducibility of the method, was 10.1%, 13.0%, and 5.7% for K1,
      k2, and p, respectively. In summary, beta-probes in conjunction with H2 15O allow
      the reproducible quantitative measurement of CBF, although some systematic
      underestimation seems to occur, probably because of partial volume effects.

PMID- 14663342
TI  - Diffusion magnetic resonance imaging study of a rat hippocampal slice model for
      acute brain injury.
AB  - Diffusion magnetic resonance imaging (MRI) provides a surrogate marker of acute
      brain pathology, yet few studies have resolved the evolution of water diffusion
      changes during the first 8 hours after acute injury, a critical period for
      therapeutic intervention. To characterize this early period, this study used a
      17.6-T wide-bore magnet to measure multicomponent water diffusion at high b
      values (7 to 8,080 s/mm(2)) for rat hippocampal slices at baseline and serially
      for 8 hours after treatment with the calcium ionophore A23187. The mean fast
      diffusing water fraction (Ffast) progressively decreased for slices treated with
      10-microM/L A23187 (-20.9 +/- 6.3% at 8 hours). Slices treated with 50-micromol/L
      A23187 had significantly reduced Ffast 80 minutes earlier than slices treated
      with 10-microM/L A23187 (P < 0.05), but otherwise, the two doses had equivalent
      effects on the diffusion properties of tissue water. Correlative histologic
      analysis showed dose-related selective vulnerability of hippocampal pyramidal
      neurons (CA1 > CA3) to pathologic swelling induced by A23187, confirming that
      particular intravoxel cell populations may contribute disproportionately to water
      diffusion changes observed by MRI after acute brain injury. These data suggest
      diffusion-weighted images at high b-values and the diffusion parameter Ffast may
      be highly sensitive correlates of cell swelling in nervous issue after acute
      injury.

PMID- 14663343
TI  - Determination of volume of distribution using likelihood estimation in graphical
      analysis: elimination of estimation bias.
AB  - The graphical analysis uses an ordinary least squares (OLS) fitting of
      transformed data to determine the total volume of distribution (VT) and is not
      dependent upon a compartmental model configuration. This method, however, suffers
      from a noise-dependent bias. Approaches for reducing this bias include
      incorporating a presmoothing step, minimizing the squared perpendicular distance
      to the regression line, and conducting multilinear analysis. The solution
      proposed by Ogden, likelihood estimation in graphical analysis (LEGA), is an
      estimation technique in the original (nontransformed) domain based upon standard
      likelihood theory that incorporates the specific assumptions made on the noise
      inherent in the measurements. To determine the impact of this new method upon the
      noise-dependent bias, we compared VT determinations by compartmental modeling,
      graphical analysis (GA), and LEGA in 36 regions of interest in dynamic PET data
      from 25 healthy volunteers injected with [11C]-WAY-100635 and [11C]-McN-5652,
      which are agents used to image the serotonin 1A receptor and serotonin
      transporter, respectively. As predicted by simulations, LEGA eliminates the noise
      dependent bias associated with GA using OLS. This method is a valuable addition
      to the tools available for the quantification of radioligand binding data in PET
      and SPECT.

PMID- 14663344
TI  - Pixel-by-pixel spatiotemporal progression of focal ischemia derived using
      quantitative perfusion and diffusion imaging.
AB  - Pixel-by-pixel spatiotemporal progression of focal ischemia (permanent occlusion)
      in rats was investigated using quantitative perfusion and diffusion magnetic
      resonance imaging every 30 minutes for 3 hours. The normal left-hemisphere
      apparent diffusion coefficient (ADC) was 0.76 +/- 0.03 x 10(-3) mm(2)/s and CBF
      was 0.7 +/- 0.3 mL x g(-1) x min(-1) (mean +/- SD, n=5). The ADC and CBF
      viability thresholds yielding the lesion volumes (LV) at 3 hours that best
      approximated the 2,3,5-triphenyltetrazolium chloride (TTC) infarct volumes (200
      +/- 30 mm(3)) at 24 hours were 0.53 +/- 0.02 x 10(-3) mm(2)/s (30% +/- 2%
      reduction) and 0.30 +/- 0.09 mL x g(-1) x min(-1) (57% +/- 11% reduction),
      respectively. Temporal evolution of the ADC- and CBF-defined LV showed a
      significant "perfusion-diffusion mismatch" up to 2 hours (P < 0.05, n = 11), a
      potential therapeutic window. Based on the viability thresholds, three pixel
      clusters were identified on the CBF-ADC scatterplots: (1) a "normal" cluster with
      normal CBF and ADC, (2) an "ischemic core" cluster with markedly reduced CBF and
      ADC, and (3) a "mismatch" cluster with reduced CBF but slightly reduced ADC.
      These clusters were color-coded and mapped onto the image and CBF-ADC spaces.
      Lesions grew peripheral and medial to the initial ADC abnormality. In contrast to
      the CBF distribution, the ADC distribution in the ischemic hemisphere was
      bimodal; the relatively time-invariant bimodal-ADC minima were 0.57 +/- 0.02 x
      10(-3) mm(2)/s (corresponding CBF 0.35 +/- 0.04 mL x g(-1) x min(-1)),
      surprisingly similar to the TTC-derived thresholds. Together, these results
      illustrate an analysis approach to systemically track the pixel-by-pixel
      spatiotemporal progression of acute ischemic brain injury.

PMID- 14663345
TI  - Sequential versus nonsequential measurement of density and affinity of dopamine
      D2 receptors with [11C]raclopride: effect of methamphetamine.
AB  - The multiple ligand concentration assays (MLCRA) method provides researchers with
      the ability to measure in vivo receptor characteristics in a stable condition.
      Measurements of the density and affinity of the dopamine D2 receptors with
      [11C]raclopride, using a sequential method (three scans throughout 1 day) or a
      nonsequential method (three scans spread over several weeks but at the same time
      of the day), yield similar values. However, after an acute challenge with drugs
      that affect dopamine neurotransmission, the concentration of endogenous ligand
      may vary over the course of the in vivo sequential MLCRA. Combined PET
      microdialysis studies after acute amphetamine showed that during the imaging time
      frame the concentrations of extracellular dopamine vary widely, but that
      nonetheless the decrease in raclopride binding potential is sustained and nearly
      constant over time. These observations apparently contradict the simple
      competitive displacement model if the changes in extracellular concentration are
      taken to reflect necessarily comparable changes at the binding sites. To
      understand the effect of the delay between drug administration and start-to-end
      of data acquisition on the MLCRA results, we compared the outcomes of the
      sequential and nonsequential methods after methamphetamine. Comparison of the
      binding potential, density, and affinity of D2 receptors in both experimental
      conditions revealed good concordance between the data sets, suggesting that
      methamphetamine produces sustained and stable increases in synaptic dopamine.

PMID- 14663346
TI  - Maturation of mismatch negativity: a scalp current density analysis.
AB  - OBJECTIVE: Auditory evoked potentials provide the opportunity to better
      understand the central processing of auditory stimuli, which is the basis of
      speech and language perception. The purpose of this study was to examine
      maturational changes in the topography of one of these auditory evoked
      potentials, the mismatch negativity (MMN), using scalp current density (SCD)
      analysis. DESIGN: Subjects were children ages 4 to 11 yr (N = 53), and adults (N
      = 12). Stimuli were 85 dB peSPL 1000 Hz standard tones and 1200 Hz deviant tones
      (deviant probability = 0.15). Auditory evoked potentials were recorded using
      surface electrodes placed at 32 locations on the head while subjects ignored the
      stimuli by watching a silent video. RESULTS: Significant maturational changes in
      topography of MMN were seen over frontal and left lateral sites. CONCLUSIONS:
      Differences in MMN for the children compared to adults indicate that the MMN
      generators or their orientation, and thus the neural processes underlying
      discrimination of simple tones, are not yet mature by 11 yr of age.

PMID- 14663347
TI  - Distance and reverberation effects on directional benefit.
AB  - OBJECTIVE: Understanding the potential benefits and limitations of directional
      hearing aids across a wide range of listening environments is important when
      counseling persons with hearing loss regarding realistic expectations for these
      devices. The purpose of this study was to examine the impact of speaker-to
      listener distance on directional benefit in two reverberant environments, in
      which the dominate noise sources were placed close to the hearing aid wearer. In
      addition, speech transmission index (STI) measures made in the test environments
      were compared to measured sentence recognition to determine if performance was
      predictable across changes in distance, reverberation and microphone mode.
      DESIGN: The aided sentence recognition, in noise, for fourteen adult participants
      with symmetrical sensorineural hearing impairment was measured in six
      environmental conditions in both directional and omnidirectional modes. A single
      room, containing four uncorrelated noise sources served as the test environment.
      The room was modified to exhibit either low (RT60 = 0.3 sec) or moderate (RT60 =
      0.9 sec) levels of reverberation. Sentence recognition was measured in both
      reverberant environments at three different speech loudspeaker-to-listener
      distances (1.2 m, 2.4 m, and 4.8 m). STI measures also were made in each of the
      12 listening conditions (2 microphone modes x 3 distances x 2 reverberation
      environments). RESULTS: A decrease in directional benefit was measured with
      increasing distance in the moderate reverberation condition. Although reduced,
      directional benefit was still present in the moderately reverberant environment
      at the farthest speech speaker-to-listener distance tested in this experiment. A
      similar decrease with increasing speaker-to-listener distance was not measured in
      the low reverberation condition. The pattern of average sentence recognition
      results across varying distances and two different reverberation times agreed
      with the pattern of STI values measured under the same conditions. CONCLUSIONS:
      Although these data support increased directional benefit in noise for reduced
      speaker-to-listener distance, some benefit was still obtained by listeners when
      listening beyond "effective" critical distance under conditions of low (300 msec)
      to moderate (900 msec) reverberation. It is assumed that the directional benefit
      was due to the reduction of the direct sound energy from the noise sources near
      the listener. The use of aided STI values for the prediction of average word
      recognition across listening conditions that differ in reverberation, microphone
      directivity, and speaker-to-listener distance also was supported.

PMID- 14663348
TI  - Activity-dependent developmental plasticity of the auditory brain stem in
      children who use cochlear implants.
AB  - OBJECTIVES: 1) To determine if a period of early auditory deprivation influences
      neural activity patterns as revealed by human auditory brain stem potentials
      evoked by electrical stimulation from a cochlear implant. 2) To examine the
      potential for plasticity in the human auditory brain stem. Specifically, we asked
      if electrically evoked auditory potentials from the auditory nerve and brain stem
      in children show evidence of development as a result of implant use. 3) To assess
      whether a sensitive or critical period exists in auditory brain stem development.
      Specifically, is there an age of implantation after which there are no longer
      developmental changes in auditory brain stem activity as revealed by electrically
      evoked potentials? DESIGN: The electrically evoked compound potential of the
      auditory nerve (ECAP) and the electrically evoked auditory brain stem response
      (EABR) were recorded repeatedly during the first year of implant use in each of
      50 children. The children all had pre- or peri-lingual onset of severe to
      profound sensorineural hearing loss and received their implants at ages ranging
      from 12 mo to 17 yr. All children received Nucleus cochlear implant devices. All
      children were in therapy and in school programs that emphasized listening and
      required the children to wear their implants consistently. RESULTS: Initial
      stimulation from the cochlear implant evoked clear responses from the auditory
      nerve and auditory brain stem in most children. There was no correlation between
      minimum latency, maximum amplitude, or slope of amplitude growth of initial
      responses with age at implantation for ECAP eN1, EABR eIII and eV components (p >
      0.05). During the first year of implant use, minimum latency of these waves
      significantly decreased (p < 0.01, p < 0.0001, p < 0.0001, respectively). Neural
      conduction time, measured using the interwave latency of ECAP eN1-EABR eIII for
      lower brain stem and EABR eIII-eV for upper brain stem, decreased during the
      period of 6 to 12 mo of cochlear implant use (p < 0.01 (lower), p <
      0.0001(upper)). The ECAP wave eN1 and the EABR wave eV showed significant
      increases in amplitude during time of implant use (p < 0.05 and p < 0.01,
      respectively). There were no correlations between the rate of interwave latency
      decrease and the rate of amplitude increases and the age at which children
      underwent implantation (p < 0.05). CONCLUSIONS: Activity in the auditory pathways
      to the level of the midbrain can be evoked by acute stimulation from a cochlear
      implant. EABR measures are not influenced by any period of auditory deprivation.
      Auditory development proceeds once the implant is activated and involves
      improvements in neural conduction velocity and neural synchrony. Underlying
      mechanisms likely include improvements in synaptic efficacy and possibly
      increased myelination. The developmental plasticity that we have shown in the
      human auditory brain stem does not appear from EABR data to be limited by a
      critical period during childhood.

PMID- 14663349
TI  - Risk factors for tinnitus in a population of older adults: the blue mountains
      hearing study.
AB  - OBJECTIVE: To identify potential and modifiable risk factors for tinnitus in a
      population of older adults. STUDY DESIGN: Cross-sectional study. Detailed
      questionnaires were interviewer-administered in a representative sample of 2015
      persons aged 55+ yr, living in an area west of Sydney, Australia. Air- and bone
      conduction audiometric thresholds were measured from 250 to 8000 Hz and from 500
      to 4000 Hz, respectively. TEOAE and SOAE were measured for both ears. RESULTS:
      After adjusting for multiple variables in a Cox proportional hazards model,
      factors that significantly increased the risk of tinnitus were poorer hearing and
      cochlear function, self-reported work-related noise exposure, and history of
      middle ear or sinus infections, severe neck injury or migraine. CONCLUSION:
      Interventions aimed at reducing age-related hearing loss, particularly by
      reducing excessive work-related noise exposure, and the effective, timely
      treatment of ear-related infections, may all decrease the risk of tinnitus.

PMID- 14663350
TI  - Audiologic manifestations of patients with post-treatment Lyme disease syndrome.
AB  - OBJECTIVE: The purpose of this study was to characterize auditory function in
      patients diagnosed with post-treatment Lyme disease syndrome (PTLDS). DESIGN:
      Eighteen patients with PTLDS were evaluated and compared to a normal population.
      Evaluations consisted of pure tone and speech thresholds, word recognition (WRS),
      acoustic immittance battery, auditory brain stem response (ABR), and loudness
      discomfort level (LDL). Both seropositive and seronegative patients were
      evaluated. Audiologists were blinded to patient status. RESULTS: Forty four
      percent of the patients had one or more abnormal pure tone thresholds compared to
      gender- and age-adjusted norms. Thirty-one percent showed abnormally reduced
      LDLs, and 17% had abnormal acoustic reflexes at one or more frequencies.
      CONCLUSIONS: This paper catalogs previously unstudied long-term auditory system
      sequelae resulting from PTLDS. Our most significant finding was the dramatically
      reduced loudness tolerance in the presence of either normal or minimally impaired
      hearing. The clinician is encouraged to consider PTLDS when confronted with these
      or similar findings in patients having history of Borrelia burgdorferi infection
      and continued complaints.

PMID- 14663351
TI  - Detection of pseudohypacusis: a prospective, randomized study of the use of
      otoacoustic emissions.
AB  - OBJECTIVES: This study was designed to evaluate the effectiveness of transient
      otoacoustic emissions in an audiological protocol used in the evaluation of
      patients suspicious of pseudohypacusis. DESIGN: This was a prospective study of
      72 adult patients suspicious of pseudohypacusis on the grounds of case history
      and inconsistent audiometric results. The subjects were randomly assigned to a
      treatment group or control group. The treatment group consisted of 42 patients
      who underwent a four-stage protocol that included (1) standard speech and pure
      tone audiometry, (2) transiently evoked otoacoustic emissions (TEOAEs) and
      tympanometry, (3) repeat modified pure-tone audiometry, and (4) auditory brain
      stem response (ABR) audiometry. The control group consisted of 30 patients, who
      underwent an identical protocol except that Stage 2 (TEOAEs and tympanometry) was
      omitted. The main outcome measure was the mean exaggeration level defined as the
      difference in mean pure tone average (PTA) between the initial and the repeat
      session (mean PTAinitial minus mean PTArepeat). RESULTS: The mean PTA (average
      threshold at 1, 2, 3, and 4 kHz) on repeat audiometry was significantly better
      than the mean PTA obtained on the initial evaluation for each group. However, the
      mean exaggeration level was significantly greater for the treatment group (35.2
      dB HL) than for the control group (11.0 dB HL). In addition, there was no
      significant difference between the mean PTArepeat (32.7 dB HL) and the mean click
      evoked ABR threshold (31.6 dB nHL) for the treatment group whereas the mean
      PTArepeat (52.9 dB HL) was significantly poorer than the click evoked ABR
      threshold (29.2 dB nHL) for the control group. CONCLUSIONS: The inclusion of
      TEOAEs and tympanometry in an audiological protocol used in the evaluation of
      patients suspicious of pseudohypacusis resulted in a significantly greater
      threshold improvement on repeat modified pure-tone audiometry when compared to
      the improvement observed for a control group in which these tests were not
      performed.

PMID- 14663352
TI  - The reception of environmental sounds through wearable tactual Aids.
AB  - OBJECTIVE: The objective of this study was to investigate the ability to identify
      environmental sounds through a wearable tactual aid. DESIGN: A test of the
      ability to identify environmental sounds was developed, employing closed sets of
      ten sounds in each of four different settings (General Home, Kitchen, Office, and
      Outdoors). The participants in the study included a group of three laboratory
      trained subjects with normal hearing and a group of three subjects with profound
      deafness who were experienced users of a tactual device (the Tactaid 7).
      Identification testing was conducted in each of the four environmental-sound
      settings using a one-interval, ten-alternative, forced-choice procedure. The
      laboratory-trained subjects received training with trial-by-trial correct-answer
      feedback, followed by testing in the absence of feedback using the Tactaid 7
      device. The experienced tactual-aid users were tested initially without feedback
      to establish baseline levels of performance derived from their prior field
      experience with the Tactaid 7. These subjects then received additional trials in
      the presence of correct-answer feedback to determine the effects of training on
      their performance. The data were summarized in terms of overall percent-correct
      identification scores and information transfer (IT) in bits. Confusion patterns
      were described using a hierarchical clustering analysis. RESULTS: Post-training
      results with the laboratory-trained subjects on the Tactaid 7 indicated that
      performance was similar for the four test environments, with percent-correct
      scores averaging 65% (and IT of 2.0 bits). For the experienced tactual-aid users,
      performance was similar across the four environments, averaging 36% correct (and
      IT of 1.4 bits) for initial testing without feedback. Scores were increased to
      60% correct (and IT of 1.9 bits) in the presence of correct-answer feedback.
      Similar trends were observed in the hierarchical-clustering analysis across both
      groups of subjects. Within each stimulus set, certain items tended to cluster
      together, whereas other items tended to appear in single-item clusters. The
      highly identified stimuli tended to be characterized by unique temporal patterns
      and confused stimuli seemed to be most similar in terms of their spectral
      characteristics. CONCLUSIONS: Through the multi-channel spectral display of the
      Tactaid 7 device, subjects were able to identify roughly 2 bits of information in
      each of four 10-item sets of sounds representative of different environmental
      settings. Temporal cues appeared to play a larger role in identification of
      sounds than spectral or intensive cues.

PMID- 14663353
TI  - Residual speech perception and cochlear implant performance in postlingually
      deafened adults.
AB  - OBJECTIVE: This study aimed at testing the post-hoc validity of the previously
      reported predictive index for postoperative cochlear implant performance, based
      on preoperative duration of deafness, and speech reception. STUDY DESIGN: Adult
      patients with postlingual severe to profound hearing loss, who were implanted
      with Cochlear Corporation CI-22 and CI-24 devices were included in this study. We
      studied the relationship between their postoperative word recognition scores and
      preoperative factors, namely, duration of deafness, and sentence recognition. We
      used the same predictive index reported in the previous study to predict their
      postoperative scores and test the model's agreement with the actual performance.
      RESULTS: We found that postoperative performance as measured by CNC word scores
      had an inverse relationship with the duration of deafness, and a direct
      correlation with the preoperative performance on CID sentence recognition tests.
      A nonlinear term [Duration / (1+CID)] was shown to improve the correlation
      coefficient of our predictive index. CONCLUSION: Some predictability of cochlear
      implant outcome is possible depending on the preoperative duration of deafness
      and speech recognition abilities. Preoperative residual speech recognition acts
      as a "trophic factor" that protects the spiral ganglion and/ or the central
      auditory pathways from degeneration. In other words, it improves the expected
      postoperative word scores.

PMID- 14663354
TI  - Acute immunodeficiency, multiple organ injury, and the pathogenesis of SARS.

PMID- 14663355
TI  - Cytokeratin 7 immunoreactivity in rectal adenocarcinomas.
AB  - Colonic mucosa typically expresses cytokeratin (CK) 20 but not CK7. This
      CK20+/CK7- profile has been used to distinguish colonic adenocarcinoma from
      others arising in the lung, breast, or genitourinary tract. CK7 expression in
      colorectal adenocarcinoma has been reported to be rare, and when present, a
      metastatic origin needs to be excluded. However, we have observed a higher
      frequency of CK7 positivity in rectal adenocarcinomas. Paraffin sections of 42
      rectal tumors (7 adenomas and 35 adenocarcinomas), 11 colonic adenocarcinomas
      proximal to the rectum, and 18 nonneoplastic rectoanal mucosa were randomly
      selected and immunostained for CK7 and CK20 with a standard avidin-biotin complex
      method. Immunoreactivity was recorded semiquantitatively. Cytoplasmic CK7
      immunoreactivity was noted in 29 of 42 (69%) rectal glandular neoplasms (3 of 7
      adenomas [43%] and 26 of 35 adenocarcinomas [74%]) and 9 of 18 (50%)
      nonneoplastic anorectal mucosal samples. In contrast, only 3 of the 11 (27%)
      colonic adenocarcinomas proximal to rectum were CK7 positive. Because of the
      relatively higher frequency of CK7 expression in rectal epithelial neoplasms,
      when CK7 is applied to distinguish primary colorectal versus metastatic origin,
      its reactivity should be interpreted with caution and should not be used as the
      sole evidence for excluding a rectal primary, particularly in tumors involving
      the rectal or pelvic region.

PMID- 14663356
TI  - Prognostic significance of laminin, laminin receptor, and bone marrow
      micrometastases in breast cancer patients: are these markers of aggressive
      behavior and metastatic potential?
AB  - Laminin is a basement membrane glycoprotein implicated in a large number of
      biologic activities of cancer progression, many of which are mediated by the
      presence of the laminin receptor (67LR) on the cell membrane. We studied the
      correlations of laminin and its receptor with standardized and new prognostic
      factors (including bone marrow micrometastases) in a series of 112 patients with
      operable breast cancers. Laminin-positive cells were detected in 60% of the
      tumors and 67LR-positive cells in 55%; both were present in 35% of the cases. No
      association was found between laminin or 67LR positivity and pathologic tumor
      size, pathologic nodal status, grading, Ki-67, estrogen receptor status,
      progesterone receptor status, or bone marrow micrometastases. The only
      statistically significant association was with menopausal status and age, with a
      higher percentage of 67LR-positive tumors among premenopausal and younger
      patients. The median follow-up was approximately 7 years. The prognosis of
      disease-free survival was similar in the laminin-positive and laminin-negative
      subjects but was significantly better in 67LR-negative patients; there were no
      significant differences in overall survival. The prognostic role of laminin and
      67LR in disease-free survival and overall survival varied according to nodal
      status. In the absence of nodal involvement, the risk of relapse (and death) was
      greater in the patients who were positive for laminin, 67LR, or both than in
      those who were negative for laminin, 67LR, or both; in the case of 4 or more
      involved nodes, the prognostic role of laminin and 67LR was reversed. These
      results did not change after adjustment for age, menopausal status, tumor status,
      nodal status, grading, or bone marrow micrometastases.

PMID- 14663357
TI  - New phenotypical and ultrastructural findings in spindle cell
      (desmoplastic/neurotropic) melanoma.
AB  - Spindle cell melanoma is a rare and distinctive variant of malignant melanoma
      that is composed of spindled neoplastic cells and includes desmoplastic and
      neurotropic melanoma. The lack of expression of several melanoma markers may
      result in a delayed or wrong diagnosis. In this study, we have analyzed in detail
      the phenotype of the tumor cells in 9 spindle cell melanomas on both paraffin
      embedded and frozen material, using melanocytic, neural, and mesenchymal markers.
      The neoplastic cells expressed the melanocytic markers S-100, Mel-CAM, and NKIC3,
      but lacked gp100 and Melan-A; tyrosinase and c-Kit were expressed in 2 of 7
      cases. Most cases expressed the neural markers p75-nerve growth factor receptor,
      neural cell adhesion molecule, and NSE. All cases expressed vimentin but lacked
      the mesenchymal markers CD34 and alpha-smooth muscle actin. Remarkably, all
      spindle cell melanomas strongly and diffusely expressed the fibroblastic markers
      Thy1 (CD90) and aminopeptidase N (CD13) and variably expressed the enzyme prolyl
      4-hydroxylase, involved in procollagen formation. The coexpression of
      melanocytic, neural, and fibroblastic markers suggests bidirectional
      differentiation of neoplastic melanocytes toward (myo)fibroblasts and Schwann
      cells, a feature that was confirmed by electron microscopy. Furthermore, the lack
      of CD90 and CD13 staining in a wide range of melanocytic lesions suggests
      specificity of these markers for spindle cell melanoma.

PMID- 14663358
TI  - Diagnostic value of microtubule-associated protein-2 in Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous carcinoma with
      neuroendocrine differentiation and a propensity for early spread to regional
      lymph nodes. Since surgical resection is the mainstay of treatment of MCC,
      differentiation of MCC from malignant lymphoma, metastatic small cell carcinoma,
      basal cell carcinoma, and malignant melanoma is very important and is sometimes
      challenging with routine histologic examination. Immunohistochemical studies may
      be required to differentiate MCC from other primary and metastatic skin
      neoplasms. Previously, the authors reported that microtubule-associated protein-2
      (MAP-2) is a sensitive and specific marker for pulmonary neoplasms with
      neuroendocrine differentiation. Because MCC is also a neuroendocrine carcinoma,
      the authors hypothesized that MAP-2 may be expressed in MCC and therefore may be
      a useful marker in establishing an accurate diagnosis. MAP-2 staining was
      demonstrated in all 14 MCCs with diffuse (10 cases) to focal (4 cases) patterns
      of immunoreactivity. No MAP-2 immunoreactivity was observed in any lymphoma (14
      cases), basal cell carcinoma (20 cases), or squamous cell carcinoma (14 cases).
      CK20 reactivity was present in 12 of 14 cases with focal (2 cases) to diffuse (10
      cases) staining having the characteristic perinuclear dot-like pattern. NSE was
      positive in 13 of 14 cases, SYN was positive in all 14 cases, CHR was positive in
      8 of 14 cases, CK7 was positive in 4 of 14 cases, and CD99 was focally positive
      in 2 cases and diffusely positive in 3 cases. MAP-2 showed a diffuse or focal
      staining of MCC with a +1 to +4 intensity in most cases. MAP-2 was positive in
      two cases of MCC that were negative for CK20 and CHR and negative or only
      slightly positive for SYN and NSE. Therefore, MAP-2 may be a valuable ancillary
      study in skin tumors suspicious for neuroendocrine origin with faint or negative
      staining with the antibodies traditionally used for diagnosing MCC. The authors
      believe this is the first study to demonstrate the utility of MAP-2 in the
      immunohistochemical workup of MCC. The authors recommend that MAP-2 be added to
      immunohistochemical panels to confirm the diagnosis of MCC.

PMID- 14663359
TI  - Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and
      hepatocellular carcinomas.
AB  - Most adrenocortical neoplasms, renal cell carcinomas, and hepatocellular
      carcinomas are diagnosed by a combination of clinical and morphologic features.
      However, occasionally this histologic differential diagnosis requires additional
      ancillary tests, such as immunohistochemistry. The authors investigated the
      potential value of A103 in the differential diagnosis of these tumors. Thirty-two
      adrenocortical neoplasms, 86 renal cell carcinomas, and 57 hepatocellular
      carcinomas were evaluated by immunohistochemistry using a monoclonal antibody
      A103 and a standard ABC method. The adrenocortical neoplasms were 21 adenomas and
      11 carcinomas. Thirty-one of the 32 adrenocortical neoplasms showed strong and
      diffuse granular cytoplasmic staining for Melan A. No nuclear reaction was
      observed. There were no differences in staining patterns between adrenocortical
      adenomas and carcinomas. With the exception of one clear cell renal cell
      carcinoma, all non-adrenocortical neoplasms were negative. The authors conclude
      that A103 is a useful addition to the immunohistochemical panel in the
      differential diagnosis of adrenocortical neoplasms from both renal cell and
      hepatocellular carcinomas. This marker, however, does not separate benign from
      malignant adrenocortical neoplasms.

PMID- 14663360
TI  - Concomitant loss of mitochondria and the DNA repair protein hOGG1 in clear cell
      carcinoma of the kidney.
AB  - The kidney is subjected to DNA oxidative damage from reactive oxygen species
      generated by free radicals and toxic metabolites, leading to formation of DNA
      base lesions. One such DNA lesion is 8-oxoguanine, which, if not sufficiently
      removed, is potentially mutagenic because it can cause G:C to T:A transversion in
      subsequent DNA replication. The human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene
      on chromosome 3, a region (3p25-26) that shows frequent loss of heterozygosity in
      clear cell renal cell carcinoma (CC-RCC), encodes for a DNA repair enzyme capable
      of excision repair of 8-oxoguanine. Of the known isoforms of the hOGG1 enzyme
      (types Ia, Ib, Ic, Id, and II), only 1, Ia, is found in the nucleus, whereas the
      rest show a mitochondrial distribution. We investigated, by an
      immunohistochemical staining method, the expression of hOGG1 protein in 40 cases
      of CC-RCC, using archival formalin-fixed tissue. To localize the hOGG1 enzyme in
      normal and tumor tissue, immuno-staining against cytochrome c, a specific
      mitochondrial enzyme, was also performed. The results showed marked reduction in
      hOGG1 expression in the majority of tumors, with complete loss of staining seen
      in 26 (65%) and moderate and weak positive staining present in 9 (22.5%) and 5
      (12.5%) of the cases, respectively. Strong hOGG1 protein expression was present
      in normal tubular epithelium, located in the mitochondria. The results correlated
      with the expression patterns of cytochrome c. The findings indicate that loss of
      hOGG1 expression may have a role in development or progression of CC-RCC.

PMID- 14663361
TI  - Interlaboratory comparison in HercepTest assessment of HER2 protein status in
      invasive breast carcinoma fixed with various formalin-based fixatives.
AB  - Although formalin-based fixatives are used in pathologic laboratories, there is
      no strictly standardized fixation protocol in Japan. To examine interlaboratory
      variation caused by different conditions of fixation in the assessment of human
      epidermal growth factor receptor (HER) 2 status on pathologic tissues, 274
      archival invasive breast carcinomas from 5 different laboratories were evaluated
      using the HercepTest. In 1 laboratory in which 10% neutral buffered formalin was
      used, as recommended by the manufacturer, the overexpression rate was 22.4% and
      fell within the statistical expected range (20%-30%) for HER2 overexpression in
      breast carcinomas. The overexpression rates in the other 4 laboratories, in which
      either 20% nonbuffered formalin or 15% neutral buffered formalin was used, were
      near the expected range for HER2 overexpression. To clarify the influence of
      prolonged formalin fixation on the HercepTest, we compared 1-day with 7-day
      fixations using 36 cases fixed with 20% nonbuffered formalin. Of the 36 cases, 7
      showed 3+ staining with 1-day fixation and sustained the same scoring results
      with 7-day fixation, although the staining intensities in these cases were
      reduced with the prolonged fixation. These results indicated that the
      immunohistochemical assessment of HER2 status with the HercepTest was
      comparatively resistant to prolonged fixation conditions and provided stable
      staining results in positive cases, particularly 3+ patients.

PMID- 14663362
TI  - Liquid-based pap smears as a source of RNA for gene expression analysis.
AB  - The Papanicolaou smear has contributed to a decrease in cervical cancer rates in
      populations that receive regular screening. However, treatment of women with
      mildly abnormal cells is problematic because the majority of these women do not
      develop neoplasia. Thus, new techniques for identification of truly precancerous
      cells are needed. Characterization of cellular gene expression patterns is now
      possible through microarray techniques that survey the expression of large
      numbers of genes simultaneously. Here we have assessed the feasibility of
      combining new microscopic and molecular technologies to determine gene expression
      patterns in cervical intraepithelial neoplasia grade 3 cells recovered from
      liquid cytology-based Papanicolaou smear slides. Laser capture microdissection
      was used to retrieve cervical cells from ThinPrep prepared slides. The quality of
      RNA recovered from these cells proved suitable for reverse transcription
      polymerase chain reaction and for T7 RNA polymerase-based linear amplification of
      messenger RNA. We developed an optimized RNA amplification protocol that
      permitted microarray gene expression profiling in samples of as few as 20
      cervical cells. This approach combining laser capture microdissection, linear RNA
      amplification, and microarray gene expression analysis will enable comparison of
      gene expression patterns between cytologically abnormal and normal cells taken
      from a single slide and may assist in the differential diagnosis of
      histologically difficult cases.

PMID- 14663363
TI  - Localization of neural cell adhesion molecule and pan-cadherin immunoreactivity
      in intrauterine growth-retarded newborn rat kidneys.
AB  - To examine the expression and distribution pattern of neural cell adhesion
      molecule (N-CAM) and pan-cadherin immunoreactivity in intrauterine growth
      retardation (IUGR) newborn kidneys, we used a rat model of maternal protein
      restriction throughout pregnancy. Weak or moderate immunoreactivity for N-CAM and
      pan-cadherin was seen in some proximal tubules, in the thick segments of Henle,
      and in the collecting tubules of the control sections. However, the number of
      tubules expressing N-CAM and pan-cadherin was increased in the IUGR group
      compared with the control group. Increased density of N-CAM and pan-cadherin
      immunoreactivity was observed mostly in the proximal tubules, in the thick
      segments of Henle, and in the collecting tubules of IUGR newborn rat kidneys.
      Furthermore, N-CAM and pan-cadherin immunoreactivity was present in the thin limb
      of Henle in the IUGR group, whereas it was absent in the control group. Glomeruli
      were negative in both groups except for some glomeruli that showed very weak N
      CAM staining in the IUGR group. Thus it was demonstrated for the first time that
      IUGR newborn rat kidneys express N-CAM and cadherin adhesion molecules at
      specific sites of the nephron.

PMID- 14663364
TI  - Multifocal epithelioid angiosarcoma of bone: a potential pitfall in the
      differential diagnosis with metastatic carcinoma.
AB  - A case of multifocal epithelioid angiosarcoma of the femur, tibia, fibula, and
      astragalus in a 54-year-old man is reported. The tumor was composed of nests and
      cords of malignant cells with epithelioid morphology, with foci of vascular
      differentiation, necrosis, and hemorrhage. By immunohistochemistry, the
      neoplastic cells showed positivity for endothelial cell markers (CD31, CD34,
      factor VIII-related antigen, and Ulex europaeus agglutinin I), epithelial markers
      (cytokeratins and epithelial membrane antigen), and vimentin. The authors'
      findings point out the need for a panel of antibodies for the careful search of
      histologic features of vascular differentiation to correctly diagnose vascular
      bone tumors with epithelioid features, especially in evaluating small core biopsy
      specimens in which a sheetlike rather than obviously vasoformative architecture
      may lead to an erroneous diagnosis of metastatic carcinoma.

PMID- 14663365
TI  - Nonmembranous HER2/neu immunohistochemical staining.

PMID- 14663366
TI  - Easier tissue macroarray ("microchop") production.

PMID- 14663367
TI  - Merkel cell carcinoma after chronic lymphocytic leukemia: case report and
      literature review.
AB  - Increasing evidence supports an association of Merkel cell carcinoma (MCC) with
      immunodeficiency and neoplasia, and the management and outcome of these patients
      requires study. This report describes a 72-year-old man with newly diagnosed
      chronic lymphocytic leukemia (CLL) who developed MCC of his right upper extremity
      and died of bone marrow metastases at 8 months. In the five previously reported
      cases of MCC after CLL, a shorter time interval between the diagnosis of CLL and
      the onset of MCC was associated with a better prognosis. In contrast, in this
      case the near simultaneous onset of CLL and MCC was followed by a rapid, lethal
      outcome.

PMID- 14663368
TI  - P-CHOP: cisplatin (P) added to the standard CHOP regimen as first-line treatment
      for aggressive non-Hodgkin lymphoma: a single-institution phase II study.
AB  - We designed the P-CHOP regimen, which involves the addition of cisplatin (P) to
      the standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
      regimen, and investigated its activity and its toxicities in a single institution
      phase II study. Twenty-two consecutive patients with untreated, aggressive, stage
      I-IV non-Hodgkin lymphoma were enrolled in the study. Cisplatin was administered
      at a dose of 40 mg/m2 on days 1 and 2, every 3 weeks; the dose and schedule of
      the other agents were identical to those used in the standard CHOP regimen. The
      complete remission (CR) rate was 86% in eligible and 80% in all the treated
      patients, which compares favorably with the CR rates of two recent randomized
      studies of CHOP versus other regimens. P-CHOP is an innovative regimen for the
      front-line treatment of aggressive non-Hodgkin lymphoma. It is feasible and
      warrants further research, which would ideally take the form of a randomized
      comparison of P-CHOP and CHOP, possibly with the addition of rituximab in both
      arms.

PMID- 14663370
TI  - Hyperfractionated radiotherapy and concomitant cisplatin for locally advanced
      laryngeal and hypopharyngeal carcinomas: final results of a single institutional
      program.
AB  - SUMMARY: ABSTRACT The purpose of this study was to achieve locoregional control
      of locally advanced laryngeal carcinoma, survival, and organ preservation using
      split hyperfractionated accelerated radiation therapy and cisplatin
      concomitantly. This study was a phase II trial of chemoradiotherapy with split
      hyperfractionated accelerated radiation therapy, 1.6 Gy per fraction given twice
      per day to a total dose of 64 to 67.2 Gy for a total of 6 weeks with a 2-week
      gap, and cisplatin 20 mg/m2, days 1 to 5, in continuous perfusion, concomitantly.
      Seventy-three patients were treated (stage IV, 64%). At a median follow-up of 55
      months for living patients, median survival was 44 months, and 5-year overall
      survival and disease-free survival were 42% and 39%, respectively. Toxicities
      included mucositis (grade III, 40%; grade IV, 28%), epithelitis (grade III, 28%).
      Of the 73 patients, 32 (44%) have continued with their larynx free of disease.
      Split hyperfractionated accelerated radiation therapy and concomitant cisplatin
      has been demonstrated to be an active treatment for locally advanced laryngeal
      carcinomas, but more active combinations of chemotherapy and radiotherapy,
      without increase of toxicity, are necessary to increase the rate of locoregional
      control, organ preservation, and survival.

PMID- 14663369
TI  - Chemoradiotherapy in the treatment of regional pancreatic carcinoma: a phase II
      study.
AB  - In locally advanced pancreatic cancer, the utilization of chemotherapy and
      radiotherapy is increasing, although in view of the reported long-term results of
      several contemporary trials, further improvements are certainly needed.
      Encouraging results using the combination of cisplatin, cytarabine, caffeine, and
      continuous infusion (CI) 5-fluorouracil (5-FU) (PACE) for the treatment of
      advanced pancreatic carcinoma prompted a phase II study using PACE followed by
      external beam radiotherapy with CI of 5-FU (PACE-RT) for localized disease. Forty
      one patients were treated with PACE-RT as adjuvant therapy after surgical
      resection (21 patients), or as primary therapy for locally advanced, unresectable
      disease (20 patients), with reevaluation for resection after completion of
      treatment. PACE consisted of cisplatin 100 mg/m2 IV on day 1, cytarabine 2 g/m2
      IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each
      cytarabine dose; and days 3 to 21, 5-FU 250 mg/m2/d given by CI. Cycles were
      repeated every 28 days. After 2 cycles of PACE, radiation therapy was given
      concurrently with 5-FU at 200 mg/m2/d. In the adjuvant setting, the tumor bed and
      the draining lymph node basin received 50.4 Gy and 45 Gy, respectively. In the
      neoadjuvant setting, the primary and regional lymph nodes were to receive 39.6 Gy
      followed by a neutron boost of 8 NGy to the gross tumor volume. Photon therapy
      was delivered at 1.8 Gy per fraction and neutron therapy at 0.8 NGy per fraction,
      5 days a week. All patients were evaluable for toxicity and survival. The most
      common toxicity was myelosuppression, with grade III to IV neutropenia occurring
      in 59% of the patients. The median survival times in the locally advanced and
      adjuvant patients were 13.4 and 18.1 months, with 1-year survival rates of 52%
      and 65%, respectively. Nine of 20 patients receiving PACE-RT for unresectable
      carcinoma had sufficient tumor regression to meet clinical criteria for
      exploration; three were resected with curative intent. The survival of these
      three patients undergoing resection after neo-adjuvant therapy was 22.4, 24.3 and
      40 months. The treatment program was active, but only moderately well tolerated.
      Modification of this regimen with newer, less toxic drugs may provide better
      results and reduced toxicity.

PMID- 14663371
TI  - Retrospective study of the treatment of urethral cancer.
AB  - Urethral cancer is rare, encompassing less than 1% of all malignancies. Optimal
      management, at present, often relies on the limited experience gained from the
      study of retrospective cases. Therefore, it is imperative to share all available
      information regarding urethral cancer treatment via reportage of pertinent cases,
      thus enabling more complete comprehension and decision-making options by both
      clinicians and researchers. A retrospective review of 18 consecutive patients
      with primary urethral cancer was performed. An analysis was performed of clinical
      stage, treatment modality, and outcome. Overall patient survival rate for this
      retrospective was 44%, with a mean follow-up of 63.5 months. Seven of 10 patients
      with low-stage diagnosis remained disease free. Comparatively, only one of eight
      patients with high-stage cancer had no apparent disease. Patients with advanced
      cancer treated with surgery alone had a shorter disease-free survival (23.3
      months) versus those treated with combination chemo/radiation therapy (45.2
      months). The major characteristic with prognostic impact was statistically found
      to be low (T1-2, N0, M0) versus high (T3-4, N1, M1) stage, as assessed by Mann
      Whitney U test (z = 2.83, p = 0.0023). Clinical staging afforded the strongest
      prognostic indication of survival. Patients with low-stage disease exhibited
      increased survival with single-modality therapy. However, patients with advanced
      cancer benefited from combined treatment using chemotherapy and radiation
      therapy.

PMID- 14663372
TI  - PET scan assessment of chemotherapy response in metastatic paraganglioma.
AB  - Paragangliomas are indolent tumors that arise from the chief cells of the
      paraganglia in the head and neck, mediastinum, and retroperitoneal regions. Less
      than 10% of paragangliomas metastasize. Paragangliomas are known to regress
      slowly and usually partially after radiation therapy, which has been attributed
      to the development of fibrosis within the abundant vascular elements of the
      tumor. Positron emission tomography (PET) scanning was used to monitor a 33-year
      old woman with recurrent paraganglioma of the carotid body with lung and bone
      metastases before and after chemotherapy with cyclophosphamide, doxorubicin
      (Adriamycin), and dacarbazine. The patient derived clinical benefit from
      chemotherapy, with marked improvement of her systemic and respiratory symptoms,
      improvement of cancer-related anemia, and normalization of chromogranin A levels.
      A response was demonstrated on PET scan with decreased [18F] fluoro-2-deoxy-d
      glucose uptake after chemotherapy, but no significant changes were detected on
      serial computed tomography (CT) scans. The patient has remained free of disease
      progression 24 months after chemotherapy completion. It is suggested that
      metabolic imaging with PET scans is superior to anatomical imaging with CT scans
      for the monitoring of patients with paragangliomas.

PMID- 14663373
TI  - Phase II study of gemcitabine and vinorelbine combination chemotherapy in
      patients with non-small-cell lung cancer not responding to previous chemotherapy.
AB  - Both gemcitabine and vinorelbine are new anticancer drugs that have shown
      activity in the treatment of chemonaive non-small-cell lung cancer (NSCLC). Their
      role in the second-line treatment of NSCLC is less clear. We conducted a phase II
      study of gemcitabine and vinorelbine combination chemotherapy in patients with
      NSCLC who had not responded to previous platinum-based chemotherapy, to assess
      the response and toxicity of this regimen. Seventeen patients were enrolled from
      September 1998 to February 2001. Treatment consisted of vinorelbine 20 mg/m2 and
      gemcitabine 800 mg/m2 intravenous infusion on days 1, 8, and 15 every 4 weeks.
      Sixty-five cycles of treatment were given, with a median of four cycles. All
      patients were evaluable for the toxicity profile, and 16 patients were evaluable
      for the response rate. The major toxicity was myelosuppression. Grade III or IV
      neutropenia occurred in 9 patients (52.9%) during treatment. Febrile neutropenia
      occurred in only 1 patient (5.9%). Grade III anemia and thrombocytopenia occurred
      in two and three patients, respectively. Other toxicities were few and mild in
      severity. After 2 cycles of treatment, 5 of 16 patients (31.3%) had a partial
      response (95% CI 8.6-64%). The median time to disease progression was 4.6 months
      and the median survival was 8.3 months. The 1-year survival rate was 34.3%. In
      conclusion, gemcitabine and vinorelbine salvage chemotherapy produces a
      relatively high response rate, low toxicity profile, and good survival in Chinese
      patients with NSCLC who have not responded to previous platinum-based
      chemotherapy. Further study is needed to confirm its activity.

PMID- 14663374
TI  - Primary squamous cell carcinoma (SqCC) of the breast.
AB  - Primary squamous cell carcinoma (SqCC) of the breast is a rare tumor that
      presents a unique biologic behavior. Thus, it challenges the justification for
      routine axillary dissection and adjuvant therapy. A MEDLINE search of all
      reported cases of primary SqCC of the breast was performed. Data on lymph node
      status, estrogen receptor (ER) and progesterone receptor (PR) status, and
      surgical and adjuvant treatment modalities were collected. We add three cases
      from our own experience. SqCC has several unique biologic characteristics; it is
      associated with a lower rate of lymph node metastasis at presentation (22% vs. 40
      60% for infiltrating ductal carcinoma [IDC]) and a significant rate of distant
      metastasis without lymph node involvement. ER and PR receptor levels are usually
      very low. Because lymph node involvement plays a lesser prognostic and
      therapeutic role in this disease, we propose a more selective approach (i.e.,
      sentinel node biopsy). The issue of adjuvant treatment remains unresolved, owing
      to lack of data. Surgical and medical treatment of SqCC of the breast should be
      tailored to fit its distinct biologic characteristics. The 5-fluorouracil
      doxorubicin-cisplatin combination may be warranted in lieu of the combinations
      used for IDC.

PMID- 14663375
TI  - Clinical evaluation using magnetic resonance imaging for patients with stage III
      cervical carcinoma treated by radiation alone in multicenter analysis: its
      usefulness and limitations in clinical practice.
AB  - To evaluate the ability of magnetic resonance imaging (MRI) to predict the
      clinical outcome, we perform retrospective multicenter analysis of patients with
      stage III disease treated with radiation alone. From three institutions, 80
      patients with stage III disease diagnosed with MRI were entered in the study.
      Seventy-eight patients received intracavitary brachytherapy with external beam
      radiotherapy. Univariate and multivariate analyses were performed to identify the
      prognostic factors for overall survival (OAS), disease-free survival (DFS),
      pelvic control (PC), and distant metastasis-free survival (DMFS). The 5-year OAS,
      DFS, PC, and DMFS rates were 59.5%, 48.7, 74.2%, and 62.5%, respectively.
      Bilateral pelvic fixation to the pelvis (p = 0.001) and patient age 50 years or
      less (p < 0.0001) were significant adverse factors for OAS. As a function of DFS,
      these were positive lymph nodes (p = 0.02), bilateral fixation to the pelvis (p =
      0.03), and younger patient age (p < 0.0001), respectively. Patient age 50 years
      or less proved to be the only significantly unfavorable factor for PC (p <
      0.0001). Larger size/volume (p < 0.05), positive lymph nodes (p = 0.03),
      bilateral pelvic disease (p = 0.02), and younger patient age (p = 0.004) were
      significantly adverse factors for DMFS. Using multivariate analysis, patient age
      50 years or less, disease with bilateral fixation, and calculated volume more
      than 100 ml proved to be significantly adverse factors for OAS and DFS. In the
      analysis of PC, only patient age 50 years or less was a significantly adverse
      factor (p = 0.0014, relative risk [RR] = 14.93). Bilateral fixation to the pelvis
      (p = 0.0055, RR = 4.032), positive lymph nodes (p = 0.0494, RR = 2.637), and
      large calculated volume (>100 ml; p = 0.0057, RR = 4.831) proved to be
      significantly adverse factors for DMFS. For patients with stage III disease,
      size/volume and lymph node status derived from MRI showed a significant
      correlation with the development of distant metastasis, but failed to predict
      locoregional control. In addition, size/volume analysis showed no apparent
      relationship with disease-free survival. For patients with stage III disease, MRI
      may provide beneficial information predicting distant metastasis, but not for
      local control.

PMID- 14663376
TI  - [Sonography in the screening for breast cancer, a fundamental value].

PMID- 14663377
TI  - [Reducing the risks in prison surroundings. Between policies and realities, the
      challenge persists].
AB  - Numerous health problems Prison population demographics have dramatically
      increased during the last thirty years and there is no element that foresees a
      forthcoming inflection of this tendency. Many studies carried out both in France
      and elsewhere have assessed the extent of the health problems both on admission
      to prison and during detention. Difficulties in reducing the risks While
      available data fully justify the need of a true risk reduction policy, there is
      an obvious lack of pragmatism and courage in many of the field workers and
      professionals. Confusion between global prevention, general measures of hygiene
      and education, and true risk reduction programmes makes the risk reduction policy
      unclear. The strategy to be adopted All efforts should be dedicated today to make
      the measures of risk reduction widely available, in particular drug maintenance
      treatments and condoms, to train prison staff, and to evaluate on a regular basis
      the clinical practices and their effects. Only a voluntarist and clear health and
      drug policy, together with a motivated prison staff, including health
      professional and administration staff, are the keys to success for an efficient
      risk reduction strategy. It is crucial to implement and to test innovative
      programs, and to regularly assess all the facets of the risk reduction policy in
      prisons.

PMID- 14663378
TI  - [Obesity and increase in transaminase, a dangerous and obvious link].

PMID- 14663379
TI  - [Survey on the treatment of hospitalised community-acquired lower respiratory
      tract infections].
AB  - OBJECTIVES: The assessment of treatment habits regarding community-acquired lower
      respiratory tract infections and comparison with current national
      recommendations. METHOD: Prospective survey of treatment habits. Patients
      hospitalised for community-acquired pneumonia in the department of internal
      medicine, the department of neurology and the department of respiratory diseases
      (127 beds) at the Sainte-Marguerite Hospital in Marseilles were included. We
      studied the socio-economical context, the presence of severity factors, the
      analysis of risk factors, the antibiotic treatments prescribed (type, route of
      administration, duration) and the outcome of the patients. RESULTS: From November
      2001 to February 2002, 98 patients with community-acquired pulmonary infections
      were included (61 men with a mean age of 72.5 years). The treatment of these
      patients conformed to guidelines in 79 cases. In 19 cases, the prescription did
      not conform (unjustified bi-therapy in 8 patients; absence of bi-therapy in
      suspected cases of intra-cellular bacteria in 4 patients; insufficient dose in 2
      patients; and non-adapted antibiotherapy in 5 patients). CONCLUSION: In the study
      conditions, the management of community-acquired pneumonia in the hospital most
      often conformed to current guidelines. Nevertheless, efforts made for initial and
      continued medical training together with the wide circulation of the guidelines
      must be continued.

PMID- 14663380
TI  - [Analysis of the factors influencing the internal reporting of nosocomial
      infections. A review of 108 notifications].
AB  - INTRODUCTION: Since July 26, 2001, the external reporting to the regional office
      of health and social affairs (Direction departementale des affaires sanitaires et
      sociales--Ddass) and the coordination centre (Comite de lutte contre les
      infections nosocomiales--Cclin) for the fight against nosocomial infections (NI)
      is mandatory. However, the modalities of internal reporting to the Clin are
      unknown. METHOD: We performed a retrospective analysis of 108 cases of NI
      reported over 23 months in 4 medical-surgical departments (MSD) with 14 to 35 NI
      reported/MSD. The distribution of the bacteria responsible was compared with that
      of the local epidemiological state (chi2 test). A correlation analysis was
      performed between the number of NI reported in each MSD and the structural
      characteristics and activity index of these MSD (Spearmann's correlation test).
      RESULTS: The NI were predominantly infections related to a catheter (43), lower
      respiratory tract (25) and infection of the site of surgery (19). Ninety were
      documented biologically, among which 10 implied multi-resistant bacteria. Ninety
      four NI were associated with the prescription of an antibiotic. Compared with the
      local epidemiological state, the NI reported generally implied multi-resistant
      bacteria (p=0.009). The other microbiological data had little implication. In
      each of the MSD, the number of cases reported was independent of: the global
      activity, the number of interventions, the mean duration of hospitalisation, the
      number of beds, the number of clinicians, the number of new patients managed and
      the chemotherapy outpatient activity. Conversely, there was a strong correlation
      between the global consumption of antibiotics (r=0.78), and the number of the
      Clin members in each MSD DMC (r=0.82). CONCLUSION: In each MSD, the internal
      reporting of NI relies on the discovery of multi-resistant bacteria, but above
      all on the implication of those involved in the fight against nosocomial
      infections.

PMID- 14663381
TI  - [A dead and calcified right ventricular hydatic cyst. The limits of imaging].
AB  - INTRODUCTION: Cardiac echinococcosis is rare and only represents around 0.5% of
      all hydatic locations. Right ventricular location is exceptional. OBSERVATION: We
      report the case of a 72 year-old man having a chronic obstructive pulmonary
      disease. During an acute respiratory failure, cardiac ultrasonography showed a
      right ventricular tumour. After respiratory stabilisation, surgical intervention
      found the tumour, the histopathological study of which concluded in a dead and
      calcified hydatic cyst. DISCUSSION: This case report demonstrates the limits of
      modern imaging and the difficulties in diagnosing a calcified right intra
      ventricular hydatidosis. It is important to emphasize the exceptional nature of
      this form and the scarcity of its localisation. Surgical treatment is crucial in
      the majority of cases and helps to confirm the diagnosis. CONCLUSION: In endemic
      areas, the discovery of an intra-cardiac tumour must evoke and eliminate
      echinococcosis. Calcification of a cardiac location remains exceptional.

PMID- 14663382
TI  - [Pregnancy from the dermatologists point of view].

PMID- 14663383
TI  - [Physiological skin changes during pregnancy].
AB  - A NATURAL PHENOMENON: Pregnancy is a period of hormone, immunological, metabolic
      and vascular changes. Modifications of the skin, mucosa and integuments are
      therefore physiological. The modifications are in pigmentation, but also affect
      nevi, the connective tissue, vessels and appendices. Modifications in
      pigmentation exist in more than 9 pregnancies out of 10 in the form of local
      melanosis. Melasma, also know as the 'pregnancy mask' or chloasma, is fairly
      rare. These disorders in pigmentation are also observed in black-skinned women.
      Changes in nevi (darker brown colour, increase in size) occur in around 15% of
      pregnancies. MODIFICATIONS IN CONNECTIVE TISSUE: Characterised by vergetures,
      affecting 60 to 90% of women, appear between the 6th and 8th month of pregnancy
      and for which there is no satisfactory treatment. Vascular modifications are
      generally proliferative and due to estrogen impregnation that affects the
      arteriolar and venous systems. Stellar angiomas are present in 50 to 70% of
      Caucasian women. Bilateral palmar erythema may also be associated with these
      angiomas. Varicose veins and varicosities of the lower limbs induced by excessive
      venous pressure are frequent, as well as oedema (salt-water retention, increased
      capillary permeability). MODIFICATIONS IN THE APPENDICES: These concern the
      activity of the sweat glands, the size of the sebaceous glands (Montgomery
      tubercles), the nails and hair growth.

PMID- 14663384
TI  - [Dermatological diseases influenced by pregnancy].
AB  - Systemic lupus erythematosus Pregnancy can trigger-off or worsen the disease (60%
      of lupus flares). The renal damage and hypertension are important prognostic
      factors. Regarding the foetus, there is a 60% risk of prematurity. The risk of
      neonatal lupus is basically related to the presence of anti-Ro-SSA and anti-La
      SSB antibodies and cannot not be foreseen. Multi-disciplinary surveillance is a
      necessity for any woman suffering from lupus and wishing to become pregnant.
      Other connective disorders Pregnancy is rare during scleroderma and has no
      influence on its progression except in the case of renal damage. Regarding
      dermatopolymyositis, pregnancy, which is rare, might trigger-off or worsen the
      disease. Bullous diseases Porphyria may be triggered-off or worsened during
      pregnancy. The various forms of pemphigus may appear or be enhanced by pregnancy.
      Various affections The influence of sarcoidosis on pregnancy is negligible.
      Complications are possible in patients exhibiting a type I or IV Ehlers-Danlos
      syndrome. Pregnancy can enhance the vascular complications of a pseudoxanthoma
      elasticum. An exacerbation is possible in the case of a type I neurofibromatosis.
      Progression varies in the case of psoriasis, atypical dermatitis, acne and
      Behcet's disease. Genital infections are frequent during pregnancy and often
      represent a risk for the infant (vaginal candidosis, viral condyloma, gonococci,
      herpes infection). Varicella The risk of severe neonatal varicella is high when
      the disease appears in the mother just before or after delivery.

PMID- 14663385
TI  - [Specific dermatoses of pregnancy].
AB  - A heterogenic group The dermatoses specifically associated with pregnancy are
      generally benign, even if they lead to great discomfort. Some of them require
      appropriate management because of the risk of maternal or foetal complications.
      Pruritus of pregnancy Corresponds to intra-hepatic cholestasis of pregnancy,
      present in 1 to 2% of pregnant women, it may place the foetus at risk of delayed
      growth, prematurity or even death in utero. Treatment relies on cholestyramine.
      Pemphigoid gestationis or herpes gestationis This is an autoimmune disease of
      pregnancy occurring in multiparous women between the 28th and 32nd week of
      amenorrhoea (once out of 5 times within the first 7 days postpartum). Diagnosis
      is confirmed by histological examination of a bullous lesion. The disease usually
      regresses spontaneously after delivery, generally within a period of 1 to 17
      months. Relapses, earlier on and more severe than during the initial episode,
      occur in 50 to 70% of subsequent pregnancies. Treatment is essentially based on
      corticosteroids: local Class II for the pauci-bullous and/or limited forms and
      general corticosteroid therapy for the severe forms. Polymorphic dermatitis of
      pregnancy This regroups various and similar entities described during pregnancy.
      They start during the third trimester of pregnancy, their clinical aspects are
      similar, their histology is non specific, the biological explorations are normal,
      direct immunofluorescence is negative, the progression is favourable for the
      mother and the child and the pathogenesis is unknown. Impetigo herpetiformis This
      exceptional dermatosis affects the primiparous woman in 80% of cases and the
      eruption usually appears during the 3rd trimester of pregnancy, or even after
      delivery. Relapses are constant during subsequent pregnancies.

PMID- 14663386
TI  - [Arterial embolisation, a welcome alternative to the surgical management of
      uterine fibromas].

PMID- 14663387
TI  - [The level of knowledge of general practitioners regarding the early phase of
      Lyme borreliosis. Survey conducted among 106 general practitioners].
AB  - OBJECTIVE: Determine the level of knowledge of the general practitioners on the
      early phase of Lyme borreliosis in an endemic area and notably to define the
      attention paid to the use and interpretation of serologic investigations for the
      treatment of patients with erythema migrans. METHOD: This was a prospective study
      conducted from May 15 to June 31, 2001 among 106 randomly selected general
      practitioners installed in Strasbourg, France. The practitioners were all
      interviewed in their private practice and by the same person. Three standardized
      questions were asked, evaluating their level of specific medical training on Lyme
      borreliosis as well as their practice regarding treatment and diagnosis of
      erythema migrans. RESULTS: One third of the general practitioners had already
      accomplished a continued medical education course on Lyme borreliosis. Half of
      them considered that the diagnosis of erythema migrans was clinical, while the
      other half believed that serological confirmation was mandatory. However, the
      answers of those having received specific education on borreliosis were right
      (p=0.0079) since in this sub-group 72% considered that the diagnosis was
      exclusively based on clinical examination, versus 41% of the untrained
      physicians. Eighty-eight percent used the recommended antibiotic regimens to
      treat erythema migrans. Three practitioners proposed an inefficient treatment
      that had exposed the patients to the risk of extra-cutaneous complications of the
      disease. CONCLUSION: Fifty percent of the general practitioners working in
      endemic areas for Lyme borreliosis still believe that seropositivity against
      Borrelia burgdorferi is required to diagnose erythema migrans, which is untrue.
      However, this study shows that a specific education on Lyme borreliosis would
      significantly improve this score.

PMID- 14663388
TI  - [Patients refused in admission to an intensive care unit. Prospective evaluation
      of the causes and outcome].
AB  - OBJECTIVES: To determine the reasons for refusing admission to an intensive care
      unit and the immediate outcome of the patients refused. METHOD: All patients
      triaged for admission to a medical intensive care unit ICU during a three-month
      period were studied prospectively. The frequency and reason for refused admission
      were studied. The immediate outcome of the refused patients, together with the
      time lapse before their subsequent management were determined. RESULTS: Out of
      251 patients, 132 (53%) were refused admission. Primary reasons for refusal was
      lack of beds (92%). Nearly one patient out of 5 was not subsequently treated in
      an intensive care unit. CONCLUSION: Some refusals could have been avoided if the
      downstream networks (short-hospitalisation, re-habilitation centres.) had been
      able to accommodate the patients proposed. Moreover, by abandoning the strategy
      of wide admission to intensive care to the benefit of a selective triage of the
      patients proposed, a certain number of refusals would probably have been avoided.
      Nevertheless, there are obvious difficulties in the application of the latter
      method.

PMID- 14663389
TI  - [Situs invertus, a mirror image].
AB  - INTRODUCTION: Situs inversus is a rare congenital abnormality often revealed in
      the childhood. In adults with acute abdomen, it's important to know this organs'
      inversus for diagnosis and surgery. OBSERVATION: A 36 year-old woman presented
      with symptoms of appendicitis; she had a complete situs inversus diagnosed in the
      childhood. Abdominal computed tomography showed signs of diverticulitis but after
      medical therapy, a colonoscopy revealed a sigmoid tumor. A left colectomy was
      performed by laparotomy without any particular problems; pathologic examination
      confirmed a colonic adenocarcinoma T3N0. DISCUSSION: Situs inversus is complete,
      incomplete or ambiguous. It may be associated with other malformations,
      especially cardiac abnormalities. When this malformation is unknown in the
      adulthood, this inversion of organs may be responsible of diagnostic
      difficulties, especially during the physical examination of an acute abdomen. If
      the patient underwent surgery, the adaptation to this inversion of organs is
      relatively easy. In the international literature, the association of this
      abnormality with colonic tumors seems to be fortuitous.

PMID- 14663390
TI  - [A severe case of nutritional botulism treated with antitoxin].

PMID- 14663391
TI  - [Speech therapy of dysarthria in Parkinson's disease].
AB  - The treatment of speech impairment, a factor of loneliness, speech therapy to
      treat dysarthria in Parkinson's disease is a fundamental aspect of patient
      management. The impact of medicinal treatment of dysarthria is controversial and
      surgery appears to worsen the problem. Various speech therapy approaches are
      relaxation, postural rehabilitation, respiration, phonation, articulation and
      prosodic re-education. AN INTERESTING METHOD: This overview underlines the
      fundamental principles of speech therapy in Parkinson's disease and compares the
      main methods and their results. We particularly insist on the Lee Silverman Voice
      Treatment (LSVT), phonation re-education method that has been widely developed in
      the United-States. Our aim is to provide better knowledge on this re-education
      method in France.

PMID- 14663392
TI  - [Bacteria and resistance to antibiotics in acute otitis media in paediatrics,
      depending on the geographical origin].
AB  - EPIDEMIOLOGY OF THE BACTERIA RESPONSIBLE: Acute otitis media (AOM) is the most
      common bacterial infection in childhood below the age of 5 years. Bacteria may be
      isolated from middle ear fluid in about two-thirds of patients. The prevalence of
      bacteria varies from one country to the next. The most common pathogens recovered
      are Streptococcus pneumoniae, Haemophilus influenzae (20-50%) and less frequently
      Moraxella catarrhalis (10%). However, several recent reports suggest an
      increasing rate of isolation of M. catarrhalis approaching 20%. Concomitant
      isolation of two or more organisms occurs in up to 10% of cases. The role of
      Group A Streptococci and Staphylococcus aureus in AOM has decreased since the use
      of antibiotics. EPIDEMIOLOGY OF ANTIMICROBIAL RESISTANCE: The recent spread of
      penicillin resistant S. pneumoniae and amoxycillin resistant H. influenzae varies
      considerably from one country to an other and appears related to the use of
      antibiotics and socio-economic conditions. A follow up of bacterial epidemiology
      and antibiotic resistance is necessary in each region of the world to define
      accurate strategies of acute otitis antibiotherapy.

PMID- 14663393
TI  - [Sub-clinical hypothyroidism, towards the end of a controversy?].
AB  - DEFINING THE PROBLEM: Sub-clinical hypothyroidism, defined as a moderate and
      isolated increase in TSH levels, is a common syndrome and is the first phase of a
      progressive disease. However its treatment remains controversial. Some
      anamnestic, clinical and biological (anti-thyroperoxidase antibodies) parameters
      contribute in identifying the patients most likely to progress towards overt
      hypothyroidism. WHAT CAN BE EXPECTED OF TREATMENT? Several clinical studies have
      described cardiovascular, neuromuscular and lipid disorders in these patients,
      but administration of levothyroxine has provided varying results and does not
      enable the distinction between a pharmacological-like intrinsic effect of the
      thyroid hormone and the true benefits imputable to the correction of TSH, in the
      absence of any large interventional study. More studies are required to better
      identify the patients who will benefit most from hormone replacement.

PMID- 14663394
TI  - [The infectious diseases emerging in the twenty-first century].

PMID- 14663395
TI  - [Can one discuss with the patients their imminent death?].

PMID- 14663396
TI  - [Euthanasia, the magic of a word].
AB  - SOME ABUSE: The problem of euthanasia is one of the greatest subjects of ethical
      controversy of our time, controversy enhanced by the ambiguity of the word. Up
      until the Seventeenth century, the word evoked the easing of terminal suffering
      by a physician. At the end of the Nineteenth century the abuse is total--the word
      means the deliberate ending of a patient's life to spare the suffering. The
      various qualifications added later (active or passive euthanasia, direct or
      indirect, voluntary or non-voluntary, involuntary...) have certainly not helped
      to clarify the situation. AMBIGUITY AND PROBLEMS OF INTERPRETATION: Even worse,
      the word itself is not unambiguous, biased etymologically by the prefix "eu" that
      provides it with a positive connotation. A survey among the general public has
      shown that the notion of euthanasia is interpreted in different ways by the
      population, which would therefore discredit a public referendum preceding its
      legalisation, which is undesiderable because of the risks of abuses. It is
      unlikely that even the best efforts for clarification would ever be able to
      eliminate the intrinsic ambiguity that now contaminates the word. TO IMPROVE THE
      SITUATION: Since it appears difficult to banish the word euthanasia from the
      medical vocabulary, it should at least be accompanied by the objective
      characterisation of the behaviour corresponding to each situation. Hence in
      difficult situations, the place of life-saving measures, of palliative care and
      of analgesic sedation could be reasonably decided on by a group, made up on a
      case by case basis, by persons having known, cared for and accompanied the
      patient.

PMID- 14663397
TI  - [Descriptive study of the patients admitted to an intensive care unit during the
      heat wave of August 2003 in France].
AB  - INTRODUCTION: Several thousands of deaths were attributed to heat stroke during
      August 2003 in France. To date, only a very few studies have analyzed the
      prognosis in the intensive care unit (ICU) of the most severely hyperthermic
      patients. METHOD: Descriptive observational study of the patients admitted to the
      intensive care unit at the Lariboisiere hospital in Paris, for heat stroke
      defined by an elevated core body temperature above 40 degrees C with central
      nervous system dysfunction, in the absence of other etiologies explaining the
      hyperthermia. RESULTS: In the Lariboisiere hospital, an elevation in the ICU
      (+143%) and hospital mortality rate (+191%) were registered during August 2003,
      in comparison with August 2002. Fifteen patients (10 men, 5 women, median age: 57
      years) were admitted to the ICU for heat stroke between the 4th and 14th of
      August 2003. Seven of them (47%) died. On admission, the occurrence of a pre
      hospital cardiac arrest, the presence of coagulation abnormalities (reduction in
      prothrombin time and in platelet count) or of an elevation in plasma lactate
      concentration were significantly associated with the risk of death in the ICU.
      Conversely, age, body temperature, coma depth on admission and convulsions were
      not predictive of death. Neurological after effects (cerebellar syndrome,
      polyneuropathy and residual brain damage) were noted in 50% of the survivors.
      DISCUSSION: Although it is possible that heat alone precipitated the death of
      very sick people, our study clearly showed that young and valid patients died of
      heat stroke and suggests the possible increase in the 2003 death rate secondary
      to the heat wave. Moreover, it is still difficult at the moment to really
      appreciate the long-term consequences for survivors who presented serious
      neurological after effects. CONCLUSION: The August 2003 heat wave resulted in an
      elevation of the hospital and ICU death rates in the Lariboisiere hospital in
      Paris. Despite adequate cooling and supportive therapies, the mortality of
      patients admitted to the ICU for heat stroke remained elevated and the
      neurological after effects severe. These preliminary results should be confirmed
      by larger cohort studies.

PMID- 14663398
TI  - [Elderly patients presenting with fever and respiratory problems in an intensive
      care unit. Diagnostic, therapeutic and prognostic impact of a systematic
      infectious disease consultation].
AB  - OBJECTIVE: To measure the impact of an infectious disease consultation on the
      morbidity and mortality in patients aged over 75 presenting with fever and
      respiratory signs and treated with antibiotics in an intensive care unit. METHOD:
      Retrospective study comparing two groups of patients having been seen or not by
      an infectious disease specialist within the first 24 hours of hospitalisation.
      The data available before prescription of the antibiotherapy by the intensive
      care physician were collected, together with the diagnostic and therapeutic
      proposals of the infectious disease specialist. Morbidity and mortality were
      assessed from the medical files and nurses charts and included: duration of fever
      and hospitalisation, complications with antibiotherapy and venous catheters and
      the cause or causes of death. RESULTS: 169 patients were included, 115 of whom
      had been seen (study group) and 54 who had not bee seen (control group) by an
      infectious disease specialist. Sixty-six percent of the infectious disease
      specialists (76/115) proposed a differential diagnosis, although a diagnostic re
      assessment was effective for only 22% of the patients in the control group (p<
      0.01). A 50% reduction in antibiotic prescriptions was observed in the study
      group. The duration of hospitalisation was greater in the study group than in the
      control group (a mean of 10 versus 7 days, p<0.01), but was unrelated to the
      consultation with a specialist. The same result was observed with the
      complications of venous catheterism (16 versus 2 cases, p =0.04). The rate of
      mortality was of 13% in both groups. CONCLUSION: The over-zealous diagnoses of
      infection are the primary cause of over-prescription of antibiotics. Despite the
      population studied, considered as fragile, the 50% reduction in antibiotics is
      without any negative prognostic impact.

PMID- 14663399
TI  - [Groove pancreatitis. Diagnostic impact of dynamic radiology].
AB  - INTRODUCTION: Described by Becker in 1973, groove pancreatitis is a rare
      segmental chronic pancreatitis affecting the groove between the head of the
      pancreas, the duodenum and the common bile duct. Mimicking pancreatic head
      carcinoma, surgical exploration is often required. OBSERVATION: Diagnosis of
      groove pancreatitis was made on computed tomography and MR imaging (groove
      fibrosis) in a 58 year-old man presenting with acute pancreatitis complicated by
      bilary and duodenal stenosis, with totally favourable outcome within 5 months
      with conservative treatment. DISCUSSION: After a general presentation,
      characterization of fibrosis of the groove by dynamic CT and MR imaging is
      emphasized (delayed enhancement of collagen fibrous tissue during the late post
      equilibrium phase) and may, in the absence of complications, avoid surgical
      exploration. CONCLUSION: Improved radiological characterization of fibrosis helps
      the diagnosis of this particular form of pancreatitis, in which surgical
      treatment is not always ineluctable.

PMID- 14663400
TI  - [Orthostatic hypotension and its treatment in the elderly].
AB  - DEFINITION CRITERIA: Orthostatic hypotension (OH) is a frequent pathology in the
      elderly, defined, since the consensus meeting in 1996, as a drop in systolic
      blood pressure of > or = 20 mmHg and/or diastolic blood pressure of > or =10
      mmHg, 1, 2 or 3 minutes after orthostatism. SEVERAL RISKS: Orthostatic
      hypotension is associated with the risk of falls and is a limiting factor in the
      patients' autonomy and quality of life. However, it is also an independent
      predictive factor of mortality, which should justify its fairly systematic
      research in the elderly. MULTIPLE CAUSES: Its multi-factor origin is enhanced by
      certain modifications related to age (autonomous nervous system, arterial wall),
      but above all by the numerous pathological situations and predominantly the
      iatrogenic disease, hypertension, or frequent situations in geriatrics such as
      anaemia and dehydration that must be systematically explored. THERAPEUTIC
      MEASURES: Its treatment relies on the elimination of the enhancing element, the
      patient's education, the wearing of elastic stockings and, at a later stage,
      administration of treatments such as midodrine.

PMID- 14663402
TI  - [How to monitor the progression of the arthritic process?].

PMID- 14663401
TI  - [Hereditary haemochromatosis].
AB  - EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the most common
      genetic disease in France. Its frequency is on average 1 out of 300 French
      individuals. It is due to excessive dietary iron absorption, leading to
      accumulation of iron in the body. Mutations of the HFE1 gene are responsible for
      the majority of the case of haemochromatosis. FROM A CLINICAL POINT OF VIEW: The
      first clinical manifestations (weakness, sexual dysfunction, arthralgia, cardiac
      symptoms, dyspnoea on effort) can occur after the age of 30 years in men and 35
      years in women (protected for longer by menstruation, pregnancy and delivery). In
      the absence of diagnosis, severe complications can develop during the 5th decade:
      nervous breakdown, arthropathy, heart failure, diabetes mellitus, cirrhosis with
      risk of progression towards carcinoma, responsible for handicaps and premature
      death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an increase in
      transferrine saturation (>45%), associated or not with excessive ferritin plasma
      levels. It is confirmed by the genetic test, showing homozygotes for the C282Y
      mutation or compound heterozygotes for the C282Y and H63D mutations on the HFE1
      gene. RMI quantifies hepatic iron loading and generally avoids the need for a
      liver biopsy. The differential diagnosis must exclude secondary iron overload due
      to chronic transfusions in congenital or acquired blood diseases, a polymetabolic
      syndrome, chronic viral or alcoholic hepatic diseases and porphyria cutanea
      tarda. EFFICIENT TREATMENT: Today, haemochromatosis is still treated by
      phlebotomy. This consists in withdrawing 400 to 500ml of blood every week at the
      initial depletion stage and subsequently a maintenance therapy in order to
      maintain ferritin levels below 50 ng/ml. Paradoxically and through ignorance,
      hereditary haemochromatosis remains a serious disease, although its diagnosis is
      easy and the treatment simple and effective.

PMID- 14663403
TI  - [The treatment of fecal incontinence].
AB  - The treatment of faecal incontinence includes: the education of the patient,
      medical therapy, biofeedback and sphincteric exercises, surgical therapy.
      Conservative, non-surgical treatment is almost always the initial therapeutic
      approach, except in those cases in which an evident defect of the sphincter
      muscle is present. Surgical treatment has seen a noteworthy increase in the last
      fifteen years as a consequence of the development of new surgical techniques.
      These techniques include: external anal sphincter plasty, pelvic floor plasties,
      sacral neuromodulation, muscular transpositions with or without
      electrostimulation, artificial anal sphincter. These procedures may be employed
      as first or second level treatment depending on the type of pathology considered
      and its aetiology. The 1st results achieved by surgical treatment authorise us to
      believe that reconversion with artificial sphincter is a valid alternative to
      graciloplasty, notwithstanding the fact that its costs are higher. Attentive pre-
      operative assessment of patients is important. Patients must be strongly
      motivated and able to manage the new condition. Although further studies are
      necessary, the degree of satisfactory of the 1st patients operated is the best
      stimulus for pursuing the development of this technique.

PMID- 14663404
TI  - Cellular changes in association with defense mechanisms in intra-abdominal
      sepsis.
AB  - Despite progress, intra-abdominal sepsis is associated with a high morbitity and
      mortality rate. Although, much effort has been made in basic research, there have
      not been any therapeutic applications as yet. The peritoneal defense system
      (innate and specific) represents the first local reaction to inflammation caused
      by bacterial invasion. It includes lymphatic absorption of bacteria,
      phagocytosis, entrenchment of inflammation and lymphocyte production (humoral and
      cellular immune). Also, the fibrin formation and degradation by intraperitoneal
      activation of coagulation and fibrinolysis plays an important role in this local
      response. The endotoxin from Gram-negative or exotoxins from Gram-positive
      bacteria cause the release of proinflammatory cytokines (TNF-alpha, IL-1betha, IL
      6) by macrophages. They act as mediators resulting in the initiation of systemic
      inflammatory response syndrome (SIRS) at first and cellular damage with multiple
      organ dysfunction syndrome (MODS) ultimately. There are two different, but
      communicated, functional departments, i.e. peritoneal and systemic compromising
      the host inflammatory response to bacterial infection. Cytokine production occurs
      in both of them.

PMID- 14663405
TI  - [Laparoscopic inguinal hernia repair "IPOM" vs "open tension free". Preliminary
      results of a prospective randomized study].
AB  - AIM: The authors report the preliminary results of a prospective comparison of
      IPOM (group A) and "open tension free" (group B) hernioplasty in 50 patients
      having a mono or bilateral primitive hernia. METHODS: In group A (26 patients)
      hernia repair was performed using "Gore-Tex DualMesh Plus biomaterial with holes
      Corduroy" and in group B (24 patients) using the patch and plug technique with
      Marlex prosthesis. RESULTS: No intraoperative complications occurred and, in
      group A, no conversion was necessary. Four minor complications were obser-ved in
      group A (10.8%): 3 seromas and 1 transient paresthesia; 5 in group B (16%): 4
      hematomas and 1 wound infection (p=n.s.). In group A only 2 patients (7.6%)
      needed analgesics after the first 24 hours and 12 patients (50%) in group B
      (p<0.001). Mean resumption of normal activity was 8 days in group A and 17 days
      in group B (p<0.001). At a 12-month-follow-up, no recurrence was reported in both
      groups. CONCLUSIONS: The results of this prospective randomized study show that
      IPOM may be not only a feasible and effective procedure in the treatment of
      recurrent and bilateral hernia or when hernia repair is performed during other
      laparoscopic procedures, but also in particular cases of primitive hernia such as
      in very active young males or heavy duty workers. However it is necessary to
      definitely ascertain the true incidence of recurrence in non limited series and
      in longer follow-up and the preliminary results of this study encourage the
      authors to complete the randomized study.

PMID- 14663406
TI  - [Laparoscopic surgery for endoscopically irretrievable colonic polyps].
AB  - AIM: The vast majority of benign colorectal neoplasms can be safely removed by
      colonoscopic polypectomy; while peduncolated polyps can be easily endoscopically
      excised, the removal of sessile polyps may be more difficult. METHODS: Between
      January 1997 and December 1998, 12 patients underwent laparoscopic or
      laparoscopic-assisted colonic resection for treatment of endoscopically
      irretrievable colonic polyps; this group was compared to 12 patients who
      underwent a laparotomic approach for polyps in the same period of time and to 23
      patients who previously underwent similar laparoscopic resections. RESULTS: There
      were no significant differences between laparoscopic and laparotomic groups.
      CONCLUSION: Laparoscopic or laparoscopic-assisted colonic resection for treatment
      of endoscopically irretrievable colonic polyps remains our preferred method of
      treating these lesions.

PMID- 14663407
TI  - [PHS Repair in femoral hernia surgery].
AB  - BACKGROUND: Since December 2000 we began to treat femoral hernias, for the first
      time in emergency, placing the underlay mesh of a PHS 168; device in the
      properitoneal space using the same anterior way well known in plug technique
      repair. The technical description and short term effectiveness, safeness and
      comfort of our new femoral prosthetic repair are reported. METHODS: Prospective
      analysis of 12 unselected consecutive female patients who underwent 12 PHS device
      femoral hernia repairs (6 in emergency with 2 intestinal resections and 6 in
      elective settings), performed from December 2000 to December 2001 at the
      Institute of General Surgery, University of Ferrara. Mean age was 61,7 (range 25
      94) and mean follow-up was 6 months (from 1 to 11). RESULTS: Mean hospital stay
      was 2.1 days (from 1 to 5). No recurrences or complications occurred. We report
      one (8.3%) 25 year old woman with moderate cruralgia which required analgesics
      assumption form more then 24 hours. CONCLUSIONS: Although our report is not
      statistical significant (recent introduction of this new technique for a low
      incidence rate pathology) actually we perform PHS device femoral hernia repair
      systematically, both in elective and emergency surgery. This new procedure
      appears as a simple, safe, effectiveness and comfortable, anterior properitoneal
      "tension-free" repair of the myopectineal region (direct inguinal hernias
      prophylaxis).

PMID- 14663408
TI  - [Treatment of familial medullary thyroid carcinoma].
AB  - Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy, which is familial
      in 25-29% of cases. Familial MTC is due to germ-line mutations in the RET proto
      oncogene. It can occur either alone or as the thyroid manifestation of MEN 2
      syndromes; the disease is inherited in an autosomal dominant fashion with age
      related penetrance. The treatment of choice is surgery. Early diagnosis and an
      adeguate initial operation provide the best chance of cure. Hence, the diagnosis
      should be made preoperatively. Genetic testing can identify almost all affected
      individuals with hereditary disease and permits prophylactic/early thyroidectomy
      in gene carriers. Total thyroidectomy and lymphadenectomy of the cervicocentral
      compartment is mandatory in all patients. In addition, bilateral dissection of
      the cervicolateral compartment should be done in all cases with more than
      microscopic disease. Plasma calcitonin is an excellent marker for postoperative
      follow-up. Treatment of persistent/recurrent disease is primarily surgical.
      Hence, a reoperative cervical lymphadenectomy should be considered in patients
      with persistently elevated calcitonin levels and no signs of distant metastases.
      Chemotherapy and external radiotherapy have little impact on the course of
      avanced disease; more promising is metabolic radiotherapy with Y90-DOTATOC in
      patients with somatostatin receptor-positive tumours.

PMID- 14663409
TI  - [Metachronus splenic metastasis of colon cancer. A case report].
AB  - Colon cancer metastases rarely involve the spleen; in the literature only 29
      cases of isolated splenic metastasis of colon cancer are reported (9 in the
      English literature and 29 in the Japanese literature). In this paper, a further
      case of isolated splenic metastasis in a 73 year- old woman, treated six years
      before with left emicolectomy for a mucinous colon cancer (Dukes B) is reported.
      A survey of the English literature shows that most of the cases had a significant
      period between the first original resection and the diagnosis of spleen
      metastasis (2-11 years). Splenectomy was performed in all the cases reported. No
      long-term follow-up has been published; therefore, it is not possible to define
      if spleen metastases of colon cancer have a better clinical behaviour than
      hepatic metastases and if splenectomy can prevent metastatic spreading of the
      disease leading to a potential survival benefit.

PMID- 14663411
TI  - [Laparoscopic deroofing of non parasitic posterolateral liver cyst. Technical
      considerations].
AB  - Laparoscopic deroofing of the solitary non parasitic cysts of the liver is a safe
      and effective procedure. This technique allows a wide access for surgical
      treatment of cysts localized in segments II, III, IVb, V, and VIII of the liver.
      On the contrary, the posterior segments, VI and VII, and the segment IVa, are
      difficult to approach laparoscopically. This report describes a laparoscopic
      technique used in treating 3 cases of symptomatic solitary cysts of the posterior
      segments of the liver. The patients were placed in the left lateral position. The
      fenestration treatment was easy and the mobilization of the right hepatic lobe
      was not required. At one year follow-up, neither postoperative complications nor
      recurring episodes were observed.

PMID- 14663410
TI  - [Solid pseudopapillary tumour of the pancreas. Report of a case].
AB  - Solid pseudopapillary pancreatic tumour is an uncommon disease including 2.7% of
      exocrine malignancies of the pancreas. Its low incidence is associated with an
      uncertain prognosis and with difficult diagnostic and therapeutic problems,
      despite routine use of ultrasonography, TC and RMN. A case of solid
      pseudopapillary pancreatic tumour in a young woman is reported: the
      clinicopathologic features, diagnostic imaging and surgical treatment are
      discussed. Surgery is the primary option. Prognosis is however not fully known.
      From a review of the literature it is suggested that these tumours should be
      regarded as potentially malignant.

PMID- 14663412
TI  - [Plastic surgery in day hospital conditions: comparison between two hospital
      models].
AB  - Personal experience of plastic surgery carried out in Day Hospital conditions is
      reported. The experience took place within the hospital structure through two
      different organisational models called here transversal and divisional
      organisation models: characteristic of the former is that it uses a dedicated
      interdivisional structure within the hospital involving the centralization of all
      day-surgery activities, whereas the latter organizes Day Surgery activities
      within the operating unit whose structures it shares. On the basis of a
      comparison between the two models we were able to note advantages and
      disadvantages. We can review our experience in brief by stating that our own
      preference went to the transversal model which presents the indubitable advantage
      of being a logistic structure which is hinged on daytime activity and is ready
      therefore to satisfy on the one hand the needs of this type of patient and, on
      the other, the needs of the structure itself in efficiency terms. We propose to
      correct the disadvantages of the transversal model which can be outlined in its
      lack of homogeneity in the pathology treated and in the subtraction of the
      criterion of clinical priority in waiting lists through the attainment of a
      critical dimensional threshold such as to permit programmable sessions with
      patients with homogeneous pathology (i.e. belonging to the same hospital unit)
      and through the maintenance of a certain number of Day Hospital beds (around 25%)
      reserved for new emergency clinical cases.

PMID- 14663413
TI  - [The axillo-pectoral muscle and Karl Langer: an anatomical variation and a rather
      unknown great anatomist].
AB  - Langer's axillo-pectoral muscle is a musculotendinous structure, that is
      transversally situated in the axilla. It is an anatomic anomaly rather unknown,
      but important for the surgeon. The anatomic description of this structure, the
      clinical signs and the surgical implications are reported. Finally, the biography
      of Langer, who gave his name to the anomaly, is outlined.

PMID- 14663414
TI  - [Vascular involvement in liver and pancreas surgery].

PMID- 14663415
TI  - [Surgery in an association of vascular and abdominal pathologies: Treatment of
      both together or in two stages? ].

PMID- 14663416
TI  - [Surgical timing of pathologies if known prior to the operation. The viewpoint of
      the abdominal surgeon].

PMID- 14663417
TI  - [How to control postoperative pain: intravenous route].
AB  - Intravenous administration of analgesic drugs is one of the most common ways to
      control post-operative pain. It can be used in almost all kinds of surgical
      interventions and particularly those of medium and high complexity. Besides, when
      other techniques are contraindicated because of clinical and/or managing
      problems, intravenous way finds its best application. Among analgesic drugs NSAID
      (ketorolac) and opioids (tramadol, morphine, buprenorphine) are most frequently
      used. As to administration techniques, elastomeric pump is, according to personal
      experience, a simple-to-manage, practical and precise device with lower cost
      respect to other administration set. Elastomeric pump is a single use reservoir
      that allows continuous administration of drugs with a uniform pre-set infusion
      speed. Finally, guide-lines, showing pre-load and infusion doses of analgesic
      drugs, based on pain intensity, are presented.

PMID- 14663418
TI  - [Postoperative pain management: epidural analgesia].
AB  - BACKGROUND: Epidural analgesia is one of the most effective regimens for
      postoperative pain relief after abdominal surgery. The use of epidural analgesia
      in high risk patients has been associated with significant decrease in surgical
      stress response, in cardiac and pulmonary morbidity, in recovery of
      gastrointestinal function and in thromboembolic events. The aim of this paper is
      to describe pain relief, side effects and recovery of gastrointestinal function
      during epidural analgesia. METHODS: During the period January 1999 to September
      2001, 590 patients undergoing elective major abdominal surgery received epidural
      analgesia. Epidural catheters were inserted at T8-T9 (upper abdominal surgery) or
      T9-T11 (lower abdominal surgery) and ropivacaine 0.5% ml 7-12 combined with
      sufentanil 30 microg or with morphine 2 mg was injected. General anesthesia was
      induced and a continuous epidural infusion of ropivacaine 0.5% 5-10 ml/h was
      begun. Postoperatively, continuous epidural administration of ropivacaine 0.2%
      plus sufentanil 0.5 microg/ml or ropivacaine 0.2% plus morphine 0.02 mg/ml was
      continued. Data on the quality of analgesia, recovery of gastrointestinal
      function and all side effects were recorded for 4 days. RESULTS: Resting and
      incident pain scores were <4 and <5; 20% of patients received a rescue dose; the
      incidence of nausea was 6%, pruritus 5%; all patients also recovered from
      postoperative ileus. CONCLUSIONS: Continuous epidural analgesia resulted in good
      pain relief, provided the best balance of analgesia and side effects and improved
      postoperative outcome.

PMID- 14663419
TI  - [Postoperative patient controlled analgesia].
AB  - Patient controlled analgesia (PCA) helps patients to achieve a better comfort
      both at rest and when dynamic pain is concerned. This aim can be reached by
      closing the feedback loop in a shorter time. The purpose is to keep drug
      concentration in the narrow therapeutic range of MEAC (minimal effective
      analgesic concentration). Two methods of administration can be used: demand
      bolus; continuous infusion rate plus demand bolus. Continuous infusion method
      together with opioids administration increases lethal complications 0.28 to 1.08%
      (p<0.05), unless patient controlled epidural analgesia (PCEA) is performed.
      Therefore, this method can be used only in ICU environment. An effective and safe
      dose delivering and a correct infusion timing is now possible due to recent
      improvement in technology. The success in PCA depends more by parameters chosen,
      patient and healthcare personnel compliance, monitoring of S(p)O(2), respiratory
      rate, pain VAS and Sedation Score than by the drug administered. There is recent
      evidence that PCA improves patient's comfort, but does not reduce the amount of
      personnel work, postoperative morbidity, analgesic consumption and costs.

PMID- 14663420
TI  - [The nurse's role in the postoperative pain management].
AB  - Ward nurses have a central role in postoperative pain management. Pain medication
      is prescribed by anesthetists and surgeons, but it is ward nurses who spend more
      time with patients and have the responsibility for assessing patient's pain
      intensity, administering some prescribed analgesic treatments and monitoring
      their efficacy. Regular monitoring of patients' pain intensity by ward nurses is
      important in assessing the standard of care provided and in early detection of
      treatment side effects. New analgesic techniques such as epidural analgesia
      require extensive, systematic monitoring by nursing staff. There is increasing
      interest in establishing close cooperation and partecipation of ward nurses in
      day- to- day management of pain. In conclusion the quality of care provided by
      ward nurses is an important factor for the quality of patients' postoperative
      care, and nursing staff should be given the support they need to effectively
      treat pain.

PMID- 14663422
TI  - [X-ray diagnostic and preoperative staging of rectal carcinoma].

PMID- 14663421
TI  - [The c-kit/Stem Cell Factor in the cancerogenetic process of colon-rectal
      carcinoma. Biological and clinical aspects].

PMID- 14663423
TI  - [Pre- and post- operative chemotherapy of rectal carcinoma. Indications and
      results].

PMID- 14663424
TI  - [Surgical errors].

PMID- 14663425
TI  - Combined uvulopalatopharyngoplasty and radiofrequency tongue base reduction for
      treatment of obstructive sleep apnea/hypopnea syndrome.
AB  - OBJECTIVE: In this study, we compare the objective results of
      uvulopalatopharyngoplasty (UPPP) combined with tongue base radiofrequency
      reduction (TBRF) with standard UPPP treatment of obstructive sleep apnea/hypopnea
      syndrome (OSAHS). STUDY DESIGN: We conducted a retrospective study of 277
      patients who had stage I, II, or III OSAHS based on the Friedman staging system
      previously presented. METHODS: One hundred thirty-four patients who had treatment
      with UPPP only were used as a control group. This included 31 patients with stage
      I, 29 patients with stage II, and 74 patients with stage III OSAHS. An additional
      143 patients with Stage II (n = 52) and III (n = 91) OSAHS were treated with
      combined UPPP and TBRF, initially and followed by additional TBRF treatments (up
      to 9000 J) as necessary. Subjective results were collected based on
      questionnaires and the Epworth Sleepiness Scale score for the experimental group,
      but these subjective measures were not available for the control group. Objective
      results were compared based on the polysomnographic findings before and after
      surgery. RESULTS: Subjectively, the study group did extremely well. Based on
      objective measures of successful treatment, UPPP plus TBRF resulted in a
      significantly higher percentage of patients who were "cured" of OSAHS compared
      with the control group. CONCLUSIONS: Stage I patients were usually successfully
      treated with UPPP only. However, patients allocated to stage II or III will
      benefit from the addition of TBRF to standard UPPP. Many UPPP-plus-TBRF patients
      in this study aborted further recommended TBRF treatments after subjective
      improvement and therefore objective results for this group, although improved in
      comparison to stage II and III patients treated with UPPP only, may not represent
      maximal potential improvement.

PMID- 14663426
TI  - Diagnosis and management of pulmonary metastasis from recurrent respiratory
      papillomatosis.
AB  - OBJECTIVE: We sought to review the current and proposed management, as well as
      bring about discussion, of managing the patient with distal tracheal and
      pulmonary parenchymal involvement by recurrent respiratory papillomatosis (RRP).
      DESIGN, SETTING, AND PATIENTS: We conducted a review of 6 patients with pulmonary
      metastasis from RRP at 3 academic tertiary care hospitals. Interventions included
      surgical and medical management with antiviral, chemotherapeutic, and/or immune
      modulating agents. RESULTS: Although treatment with alpha-2-beta interferon,
      isotretinoin, and methotrexate have not proved to eradicate pulmonary involvement
      by RRP, possible epithelial stabilization and slowing of disease progression are
      noted. CONCLUSIONS: The rates of distal tracheal and pulmonary metastasis as seen
      in our cohort were higher than previously reported. Approximately 12% of our
      patients with RRP have distal tracheal spread and as many as 7% of all patients
      with RRP at our institutions have pulmonary dissemination. Also, high suspicion
      for malignant conversion to squamous carcinoma in the patient with pulmonary
      spread should be maintained. In addition, aggressive treatment, although not
      proved to eradicate the pulmonary disease, should be undertaken due to the high
      morbidity and mortality associated with pulmonary dissemination of RRP in our
      cohort.

PMID- 14663427
TI  - Endoscopic CO2 laser surgery for large synovial sarcoma of the larynx.

PMID- 14663428
TI  - The effect of bolus consistency on dysphagia in unilateral vocal cord paralysis.
AB  - OBJECTIVE: To examine the risk of aspiration for liquid versus paste bolus
      consistencies in patients with unilateral vocal cord paralysis (UVCP). METHODS:
      The swallowing function of adult patients with UVCP was prospectively studied
      videofluorographically to examine the incidence of laryngeal penetration and
      aspiration for both liquid and paste boluses. The degree of penetration or
      aspiration was quantified using the penetration-aspiration scale (PAS). The
      presence and location of pharyngeal bolus residue were also documented for each
      consistency. Results were compared between liquid and paste bolus consistencies.
      RESULTS: Fifty-five patients with UVCP were studied with a mean age of 60.2
      years. Intrathoracic surgery or malignancy accounted for 38 (69.1%) of cases. The
      mean PAS scores for liquid and paste bolus consistency were 3.1 vs. 1.5,
      respectively (P < 0.001). The liquid bolus penetrated in 19 (34.5%) patients and
      was aspirated in 11 (20%) patients. In contrast, the paste bolus penetrated in 12
      (21.8%) cases and was aspirated in 0 cases (P < 0.001). Pharyngeal residue was
      more likely to occur at the base of the tongue or vallecula for the paste bolus
      consistency versus the liquid bolus. CONCLUSIONS: A significant percentage of
      patients with UVCP will aspirate thin liquids. Paste bolus consistencies are
      safer for patients with UVCP as they are much less likely to lead to penetration
      or aspiration despite a higher prevalence of pharyngeal residue.

PMID- 14663429
TI  - Molecular genetic advances in semicircular canal abnormalities and sensorineural
      hearing loss: a report of 16 cases.
AB  - OBJECTIVES: The study goals were (1) to determine if the degree and pattern of
      semicircular canal dysmorphology and the presence or absence of a cochlea in
      patients with congenital sensorineural hearing loss predict audiologic outcome,
      severity, or the frequencies involved and (2) to review the recent advances in
      molecular genetics of the semicircular canals and correlate this information with
      audiologic and anatomic patterns seen in our series of patients. DESIGN AND
      SETTING: We conducted a retrospective study at a tertiary care center with a
      large otologic and cochlear implant service. PATIENTS AND METHODS: The study
      population consisted of 16 patients with congenital sensorineural hearing loss in
      28 congenitally malformed inner ears consisting of semicircular canal dysplasia
      or aplasia, with or without cochlear malformation. History, physical examination,
      computed tomography scans, and serial audiograms were reviewed. Factors analyzed
      included other phenotypic dysmorphology characteristic of syndromes, audiometric
      configuration, severity and type of hearing loss, and the presence of associated
      inner ear anomalies other than the vestibular system. An extensive review of the
      literature regarding molecular genetic factors in semicircular canal anomalies,
      with or without cochlear abnormalities, was performed. RESULTS: Sixteen patients
      (31 ears) were identified with profound sensorineural hearing loss and
      semicircular canal abnormalities. Only 3 patients had known syndromes, although 4
      patients had other congenital anomalies. Most radiographic detectable
      abnormalities were bilateral. Audiograms of the patients demonstrated pure tone
      averages between 90 and 100 dB in the affected ears with few exceptions. No
      correlation was found between type and severity of malformation of either the
      cochlea or semicircular canals with the severity of hearing loss. There was no
      stepwise progression of hearing loss increasing malformation severity. Seven of
      the 16 patients received cochlear implants. Of these 7, 3 patients had cochlear
      hypoplasia and 1 patient had a common cavity deformity. Audiologic follow-up on
      all 7 patients revealed improvement in both speech assessment threshold and pure
      tone average. Presence or absence of the cochlea was not a factor in outcome
      after cochlear implantation. CONCLUSION: We have assembled the largest series of
      patients with semicircular canal dysmorphology, with or without various cochlear
      abnormalities. Our study failed to correlate the type and severity of
      semicircular canal malformation with any specific audiologic outcome. The
      variation in hearing loss severity and pattern even in patients with similar bony
      radiographic findings must be explained by other non-radiologically detectable
      defects, likely abnormalities in membranous labyrinthine development. New
      molecular genetic discoveries have linked specific genes to the development of
      certain inner ear structures in mice studies. The independent development of the
      individual semicircular canals in relation to the cochlea and vestibule and the
      variability in hearing loss suggest a more complex embryologic process than
      merely an arrest in development as previously thought. As genetic studies are
      extended into humans, we will likely be able to stratify these patients by
      molecular defect and severity of hearing loss.

PMID- 14663430
TI  - Tympanic membrane metalloproteinase inflammatory response.
AB  - OBJECTIVE: The goal of this study was to determine whether expression of matrix
      metalloproteinases (MMP) in tympanic membranes (TM) is stimulated by host tumor
      necrosis factor-alpha (TNF-alpha) and bacterial toxin (lipopolysaccharide, LPS),
      which may play a role in the pathogenesis of cholesteatoma. STUDY DESIGN: Gerbil
      TMs (n = 48) were cultured in the presence of either TNF-alpha or LPS.
      Quantitative analysis of TNF-alpha and MMPs was performed on both the homogenized
      TMs and the culture media supernatant. RESULTS: Levels of TNF-alpha and MMPs did
      not increase significantly in TMs with exposure to inflammatory mediators. TNF
      alpha levels in supernatant were elevated (P < 0.007) with more concentrated LPS
      exposure. Supernatant levels of MMP2 were increased (P < 0.007) at most
      concentrations of LPS and TNF-alpha. CONCLUSION: Cultured TMs expressed MMPs in
      response to bacterial and host inflammatory mediators. These findings support a
      link between inflammation and the secretion of potentially destructive MMPs in
      the TM, which may contribute to the pathogenesis of cholesteatoma.

PMID- 14663431
TI  - Age-related changes in the vestibular-evoked myogenic potentials.
AB  - OBJECTIVE: We sought to investigate the effects of gender and age on the
      vestibular-evoked myogenic potential (VEMP). STUDY DESIGN AND SETTINGS: Sixty
      healthy adult volunteers (28 male and 32 female) were investigated in this study.
      The subject age was distributed between 20 and 77 years old. RESULTS: No gender
      related differences were detected in the VEMP. There was a significant
      correlation between age and both the evoking threshold and the pInII amplitude of
      the VEMP, whereas no significant correlation was observed between age and left
      right differences of the VEMP. CONCLUSIONS: The correlation between age and the
      parameters of the VEMP is presumably secondary to age-related functional changes
      in the sensory and neural elements of the VEMP. It is safe to evaluate the VEMP
      using the value of the non-affected side when assessing unilateral lesions.
      However, it may be necessary to take age into account in evaluating the VEMP when
      bilateral lesions are suspected.

PMID- 14663432
TI  - Long-term hearing preservation after middle fossa removal of vestibular
      schwannoma.
AB  - OBJECTIVE: We sought to determine long-term hearing preservation in vestibular
      schwannoma patients after undergoing middle fossa resection. STUDY DESIGN,
      SETTING, AND OUTCOME MEASURES: We conducted a retrospective chart review of
      patients undergoing middle fossa resection from 1990 to 1995 at a tertiary care
      center. Pure-tone thresholds, before resection and at least 5 years after
      resection, and speech discrimination scores are reported. RESULTS: Seventy
      percent of patients with immediate postoperative hearing maintained serviceable
      hearing at more than 5 years after surgery. Pure-tone average in the operative
      ear changed at the same rate as hearing in the unoperated ear during this follow
      up period. CONCLUSIONS: More than two thirds of patients who underwent middle
      fossa resection of a vestibular schwannoma with some hearing postoperatively
      maintain that hearing at greater than 5 years of follow-up. Surgery alone does
      not have a negative impact on long-term hearing preservation.

PMID- 14663433
TI  - Hearing loss with stapedotomy in otitis media.
AB  - OBJECTIVE: Stapes fixation is often found in patients with either active or
      inactive otitis media (OM). Stapedotomy is generally not performed in ears with
      OM because of the potential risk of sensorineural hearing loss (SNHL). Recent
      studies have demonstrated that the inner ear may be fenestrated in the presence
      of OM without significantly increased risk of SNHL. The goal of this study was to
      determine if stapedotomy in the presence of OM significantly increases the
      incidence of postoperative SNHL. METHODS: Streptococcus pneumoniae or Pseudomonas
      aeruginosa was injected bilaterally into the middle ears of guinea pigs (n = 18
      and 16, respectively). A control group (n = 14) was injected with saline
      solution. Two days postinjection, a unilateral stapedotomy was performed.
      Auditory thresholds were evaluated by electrocochleography before and after
      stapedotomy. RESULTS: Bacterial OM was induced in all ears injected with
      pneumococci and pseudomonas. Auditory thresholds increased in all ears treated
      with stapedotomy. Stapedotomy performed in the presence of pseudomonas OM
      resulted in significantly greater SNHL than in control or pneumococcal ears (P =
      0.0055). Hearing thresholds were not significantly different between pneumococcal
      OM and control ears treated with stapedotomy. CONCLUSION: Stapedotomy in the
      presence of pseudomonas OM, but not pneumococcal OM, significantly increases the
      risk of SNHL in the guinea pig model. SIGNIFICANCE: Stapedotomy should be avoided
      in patients with active OM, particularly in the presence of pseudomonas.

PMID- 14663434
TI  - Surgical treatment of otosclerosis in elderly patients.
AB  - OBJECTIVE: The aim of this study was to analyze hearing results of stapes surgery
      in otosclerotic patients older than 65 years. STUDY DESIGN: Among 473 primary
      stapedectomies, 16 were performed in patients over 65 years old and were
      retrospectively reviewed. Hearing results were compared with those of a randomly
      selected group of 16 patients younger than 65 years old. RESULTS: Improvement in
      hearing (closure of the air-bone gap to <20 dB) was achieved in all of the cases,
      and closure of the air-bone gap to less than 10 dB occurred in 87.5% at 1 month
      and in 81.8% at the last evaluation (mean follow-up, 19.5 months). Hearing
      results were similar in elderly and younger patients. CONCLUSION AND
      SIGNIFICANCE: Stapes surgery is an effective procedure in elderly patients with
      otosclerosis to avoid hearing aid use or to facilitate hearing aid fitting.

PMID- 14663435
TI  - The endoscopic modified Lothrop procedure for salvage of chronic frontal
      sinusitis after osteoplastic flap failure.
AB  - OBJECTIVE: While reported results utilizing the osteoplastic flap procedure are
      very good, some patients fail the surgery due to recurrent or persistent frontal
      sinus disease. This study was performed to evaluate the utility of the endoscopic
      modified Lothrop sinus surgery for osteoplastic flap failure. STUDY DESIGN AND
      SETTING: A retrospective chart analysis and telephone survey of 10 patients from
      outside our institution for whom an osteoplastic flap with fat obliteration
      failed were salvaged using a computerized endoscopic modified Lothrop procedure.
      RESULTS: The main complaints were headache/pressure and recurrent infection. The
      usual pathology was chronic sinusitis and/or mucocele. The frontal recess and
      floor of the frontal sinus were the most common areas of persistent disease.
      Symptomatic clinical improvement was noted in more than 90% of patients.
      CONCLUSION: Salvage endoscopic modified Lothrop sinus surgery is recommended for
      a limited number of traditional osteoplastic flap failures. Computerized surgical
      navigation may help avoid complications in situations with abnormal anatomy and
      previous dissection. SIGNIFICANCE: The endoscopic modified Lothrop procedure
      should be considered to salvage failed osteoplastic flap sinus obliteration.

PMID- 14663436
TI  - Endoscopic removal of juvenile angiofibromas.
AB  - BACKGROUND: Angiofibromas have traditionally been removed through open
      procedures. All tumors in this consecutive series of patients were removed
      endoscopically. SETTING: Tertiary care hospital. MATERIALS AND METHODS: Seven
      consecutive patients presenting with an angiofibroma between 1994 and 2000 were
      included in the study. Tumor size varied with 1 stage 1, 2 stage IIa, 3 stage
      IIb, and 1 stage IIC according to the Radkowski et al classification. The
      surgical technique is presented. RESULTS: After an average of 3.75 years (SD, 1.9
      years), there have been no tumor recurrences. CONCLUSION: Endoscopic removal of
      angiofibromas in the nasal cavity, with extension into the sinuses and
      pterygopalatine fossa and with limited extension into the infratemporal fossa,
      can be removed endoscopically with a good success rate.

PMID- 14663437
TI  - Microscopic anatomy of the infraorbital canal, nerve, and foramen.
AB  - OBJECTIVE: We performed this study to investigate the morphologic and topographic
      anatomy, and variations of the infraorbital canal (IOC), infraorbital nerve
      (ION), and infraorbital foramen (IOF). STUDY DESIGN AND SETTING: This study was
      performed at the Anatomy Department of Ankara University School of Medicine
      between 1999 and 2000. The morphometry of these anatomic areas on cadaver heads
      were studied microscopically. The morphologic and topograpic anatomies of IOC,
      ION, and IOF were carried out microscopically with x 25 to x 40 magnification on
      10 cadaver heads (20 sides). RESULTS: We found the shape of the IOF as oval in
      30% (6 sides), round in 40% (8 sides), and semilunar in 30% (6 sides) of the
      cadaver heads. We detected the IOF as single in 90% (18 sides), double in 5% (1
      side), and triple in 5% (1 side) of the cases. We determined a complete roof (we
      called it as "canal") in 50% of cases and groove plus canal in 50% of the heads.
      The mediolateral relationship of the vessels to the nerve while emerging from the
      IOF was investigated, and the artery was always found in a mediosuperior position
      and the vein was inferior to it. In all specimens, the ION was found to be
      consisting of 3 to 8 fascicles interwoven with the artery and the vein in the
      loose connective tissue sheath. CONCLUSION: A detailed knowledge of the anatomic
      morphometry of this area is necessary for a surgeon while performing
      maxillofacial surgery and regional block anesthesia. Anatomic variations on this
      area may take place and a surgeon must take this into consideration so as to
      increase the surgical success.

PMID- 14663438
TI  - The role of chromosomal translocation (15;19) in the carcinoma of the upper
      aerodigestive tract in children.
AB  - OBJECTIVE: To further evaluate the role of chromosomal translocation (15;19) in
      the presentation of the carcinoma (CA) of the upper aerodigestive tract. STUDY
      DESIGN AND SETTING: A retrospective study at a tertiary care pediatric medical
      center. RESULTS: Seven patients with a mean age of 12 years presented with CA of
      nasopharynx (N = 2), sinonasal region (N = I), parotid gland (N = 2), or larynx
      (N = 2). Treatments included combinations of surgery (N = 5), chemotherapy (N =
      5), and radiation therapy (N = 4). One patient with sinonasal CA and one patient
      with laryngeal CA had chromosomal translocation (15;19); these patients both died
      of their disease with a mean survival of 6 months. The 5 patients without
      translocation (15;19) responded well to treatment and are disease-free with a
      mean follow-up of 47 months. CONCLUSION: The preliminary results appear to
      indicate poor prognosis associated with the presentation of chromosomal
      translocation (15;19) despite aggressive multi-modality treatment. Further
      investigation is needed to better understand the cause and relationship of the
      translocation (15;19) and aggressive behavior of these tumors.

PMID- 14663439
TI  - Multicenter study assessing effects of heat and moisture exchanger use on
      respiratory symptoms and voice quality in laryngectomized individuals.
AB  - OBJECTIVE: A multicenter study based in the United States assessed the heat
      moisture exchanger effect on respiratory symptoms and "voice quality" of
      laryngectomees. PATIENTS AND MEASURES: The study group consisted of 81
      consecutive laryngectomees (62 men and 19 women; mean age, 66 years; age range,
      45 to 89 years), with a median follow-up of 3.5 years (range, 0.5 to 24 years). A
      structured questionnaire was used to assess 3-month results, and tally sheets
      recorded the frequency of cough-expectoration during first and last trial weeks.
      RESULTS: Compliance was 73% (n = 59); decrease in coughing, 68%; sputum
      production, 73%; forced expectoration, 60%; and need for stoma cleaning, 52% of
      these 59 patients. Regarding daily cough-expectoration frequency, a statistically
      significant decrease (P < 0.0001) was found between the first and last trial
      weeks. Regarding influence on voice quality, 46% of regular users reported
      improvement in intelligibility, 30% in loudness, 37% in fluency, and 40% in
      telephone intelligibility. Fourteen patients (19%) reported skin irritation, with
      discontinuation of 7 patients. CONCLUSION: The observed decrease in pulmonary
      symptoms and improvement in voice quality confirm earlier reports from the
      Netherlands, United Kingdom, and Spain indicating improvement in postlaryngectomy
      quality of life.

PMID- 14663440
TI  - Posterior marginal mandibulectomy in the management of cancer of the oral cavity
      and oropharynx.
AB  - OBJECTIVE: To review a single institution's experience with posterior marginal
      (ramus) mandibulectomy for mandibular preservation in the management of patients
      with squamous cell carcinoma of the retromolar trigone or oropharynx. To review
      the history and surgical technique with emphasis on functional as well as
      oncologic outcomes. STUDY DESIGN AND SETTING: Retrospective review at a tertiary
      care academic referral center from 1996 to 2002. RESULTS: Between 1996 and 2002,
      382 patients with squamous cell carcinoma of the oral cavity and oropharynx were
      surgically treated at the Loyola University Medical Center. Medical records were
      reviewed and 152 patients were identified who had some form of mandibular
      procedure (segmental resection, marginal resection, or mandibulotomy) performed
      in conjunction with their tumor resection. Eighteen posterior marginal
      mandibulectomies were performed for primary cancers of the retromolar trigone,
      tonsillar fossa, and/or base of the tongue. All patients received adjuvant
      radiotherapy. Bone invasion of the marginal mandibulectomy specimens by squamous
      cell carcinoma was observed in 2 cases, neither of which developed a local
      recurrence. Mean and median overall survivals were 41.4 and 37.5 months,
      respectively. Functional outcomes were determined by administering the University
      of Washington Quality of Life instrument administered at 12 months. Patients
      reported significant alterations in chewing, but all were able to maintain
      satisfactory oral intake and no patient required a gastrosotomy tube.
      CONCLUSIONS: A posterior osteotomy of the mandibular ramus is a useful adjunct in
      the surgical treatment of cancer of the retromolar trigone or oropharynx.
      Negative surgical margins can be obtained even with focal invasion of mandibular
      bone. The loss of bone in this area does not significantly affect patients'
      appearance. Patients report deterioration in chewing following this procedure but
      are able to maintain a diet of solid food.

PMID- 14663441
TI  - Salivary duct carcinoma.
AB  - Salivary duct carcinoma (SDC) is a highly malignant tumor that is histologically
      similar to ductal carcinoma of the breast. This article presents the
      clinicopathologic features of 15 patients with SDC arising in the salivary
      glands. The majority of patients were male and aged 65 years or older. The tumor
      was most often located in the parotid gland. Pain, facial palsy, and presence of
      calcification in the CT scan were diagnostic features suggestive of SDC.
      Histologically, 27% of the tumors arose from pre-existing pleomorphic adenoma.
      Perineural and lymphatic invasion were common findings. There was an extensive
      cervical lymph node involvement (73%). Distant metastasis was the most common
      cause of failure. Although SDC exhibits an unpredictable clinical course, total
      parotidectomy with neck dissection and adjunctive radiation therapy appear to be
      appropriate for local and regional control of this aggressive neoplasm.

PMID- 14663442
TI  - Comparison of computed tomography and magnetic resonance imaging in the diagnosis
      of parotid tumors.
AB  - OBJECTIVE: The role of computed tomography (CT) and magnetic resonance imaging
      (MRI) in the diagnosis of parotid tumors was investigated. METHODS: Forty
      patients with the clinical suspicion of a parotid mass underwent both CT and MRI
      of the parotid region. Two radiologists independently assessed the CT and MRI
      results with respect to tumor localization, tumor margin characteristics, and
      infiltration of surrounding tissue. Histopathologic specimens were obtained in
      all cases and correlated with the radiologic findings. RESULTS: The sensitivity
      and specificity of CT and MRI were nearly the same for tumor location, tumor
      margin, and tumor infiltration. CONCLUSION: The 2 imaging techniques provided the
      same information with respect to the presurgical planning and contribute to the
      diagnosis and therapy planning of parotid tumors.

PMID- 14663443
TI  - Thyroid function studies in patients with cancer of the larynx: preliminary
      evaluation.
AB  - OBJECTIVE: Our goal was to evaluate thyroid function before and after surgery
      only or radiotherapy plus surgery for laryngeal neoplasms. STUDY DESIGN AND
      SETTING: The study group consisted of a total of 30 patients with laryngeal
      cancer (22 treated with surgery only and 8 treated with surgery plus
      radiotherapy) who were evaluated by ultrasensitive thyroid-stimulating hormone,
      free T4, and antithyroid antibodies both preoperatively and at 6 and 12 months
      after surgery. RESULTS: All patients had normal thyroid function before treatment
      (1 patient had elevated antithyroid autoantibodies); after 1 year, 4 (13.34%)
      patients were hypothyroid. In 3 patients, it was subclinical (ie, elevated
      thyroid-stimulating hormone with normal free T4), and in 1 patient, it was
      symptomatic. CONCLUSION: Our preliminary data suggest that hypothyroidism occurs
      in a small but substantial proportion of patients undergoing surgery with or
      without adjuvant radiotherapy for laryngeal cancer. SIGNIFICANCE: Thyroid hormone
      dosing should be routinely included in the assessment of patients with laryngeal
      cancer, because it is simple and inexpensive and may allow the early diagnosis
      and management of hypothyroidism.

PMID- 14663444
TI  - The safety of intranasal steroids.
AB  - The increasing use of intranasal steroids in the management of allergic rhinitis
      reflects their efficacy, tolerability, and safety. However, issues related to the
      safety of intranasal steroids continue to generate debate and confusion among
      clinicians. Consequently, there is often reluctance and uncertainty in
      prescribing these effective agents for the treatment of perennial and seasonal
      allergic rhinitis. Issues of particular concern are whether intranasal steroids
      adversely affect various homeostatic systems, influence growth and bone
      metabolism, and compromise ocular function. Furthermore, the expanding role of
      intranasal steroids in the pediatric, geriatric, and postmenopausal populations
      has raised concerns that these agents may result in a steroid burden that more
      readily causes adverse effects. An extensive review of the literature
      overwhelmingly supports the assertion that intranasal steroids are safe in
      prescribed doses and should allay the misconceptions regarding their appropriate
      use in the management of allergic rhinitis.

PMID- 14663445
TI  - Metastasis to the petrous apex: a report of an uncommon case.

PMID- 14663446
TI  - Ecthyma gangrenosum of the nasal cavity.

PMID- 14663447
TI  - Breast carcinoma metastatic to the sphenoid sinus: a case report.

PMID- 14663448
TI  - Is tympanostomy tube the only option?

PMID- 14663452
TI  - Managing risk in healthy subjects participating in clinical research.

PMID- 14663453
TI  - Ethical issues in research with healthy volunteers: risk-benefit assessment.

PMID- 14663454
TI  - Use of nicotine patches in breast-feeding mothers: transfer of nicotine and
      cotinine into human milk.
AB  - OBJECTIVE: Our objective was to assess the extent of exposure to nicotine and
      cotinine in breast-fed infants during maternal smoking and later during maternal
      use of the nicotine transdermal patch to achieve smoking cessation. METHODS:
      Fifteen lactating women (mean age, 32 years; mean weight, 72 kg) who were smokers
      (mean of 17 cigarettes per day) participated in a trial of the nicotine patch to
      assist in smoking cessation. Serial milk samples were collected from the women
      over sequential 24-hour periods when they were smoking and when they were
      stabilized on the 21-mg/d, 14-mg/d, and 7-mg/d nicotine patches. Nicotine and
      cotinine in milk were quantified by HPLC, and infant dose was calculated. Plasma
      concentrations of nicotine in the breast-fed infants were assessed, and the
      infants were also clinically assessed. RESULTS: Nicotine and cotinine
      concentrations in milk were not significantly different between smoking (mean of
      17 cigarettes per day) and the 21-mg/d patch, but concentrations were
      significantly lower (P <.05) when patients were using the 14-mg/d and 7-mg/d
      patches than when smoking. There was also a downward trend in absolute infant
      dose (nicotine equivalents) from smoking or the 21-mg patch through to the 14-mg
      and 7-mg patches (P <.05 at both 14-mg and 7-mg doses, compared with smoking).
      Milk intake (shown as median and 25th to 75th percentile) by the breast-fed
      infants was similar while their mothers were smoking (585 mL/d [507-755 mL/d])
      and subsequently when their mothers were using the 21-mg (717 mL/d [504-776
      mL/d]), 14-mg (731 mL/d [535-864 mL/d]), and 7-mg (619 mL/d [520-706 mL/d])
      patches (chi(2) = 3.19, P =.364). CONCLUSIONS: We conclude that the absolute
      infant dose of nicotine and its metabolite cotinine decreases by about 70% from
      when subjects were smoking or using the 21-mg patch to when they were using the 7
      mg patch. In addition, use of the nicotine patch had no significant influence on
      the milk intake by the breast-fed infant. Undertaking maternal smoking cessation
      with the nicotine patch is, therefore, a safer option than continued smoking.

PMID- 14663455
TI  - The interaction between St John's wort and an oral contraceptive.
AB  - OBJECTIVES: The popular herbal remedy St John's wort is an inducer of cytochrome
      P450 (CYP) 3A enzymes and may reduce the efficacy of oral contraceptives.
      Therefore we evaluated the effect of St John's wort on the disposition and
      efficacy of Ortho-Novum 1/35 (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a
      popular combination oral contraceptive pill containing ethinyl estradiol (INN,
      ethinylestradiol) and norethindrone (INN, norethisterone). METHODS: Twelve
      healthy premenopausal women who were using oral contraception (>3 months)
      received a combination oral contraceptive pill (Ortho-Novum 1/35) for 3
      consecutive 28-day menstrual cycles. During the second and third cycles, the
      participants received 300 mg St John's wort 3 times a day. The serum
      concentrations of ethinyl estradiol (day 7), norethindrone (day 7), follicle
      stimulating hormone (days 12-16), luteinizing hormone (days 12-16), progesterone
      (day 21), and intravenous and oral midazolam (days 22 and 23) were determined in
      serial blood samples. The incidence of breakthrough bleeding was quantified
      during the first and third cycles. RESULTS: Concomitant use of St John's wort was
      associated with a significant (P <.05) increase in the oral clearance of
      norethindrone (8.2 +/- 2.7 L/h to 9.5 +/- 3.4 L/h, P =.042) and a significant
      reduction in the half-life of ethinyl estradiol (23.4 +/- 19.5 hours to 12.2 +/-
      7.1 hours, P =.023). The oral clearance of midazolam was significantly increased
      (109.2 +/- 47.9 L/h to 166.7 +/- 81.3 L/h, P =.007) during St John's wort
      administration, but the systemic clearance of midazolam was unchanged (37.7 +/-
      11.3 L/h to 39.0 +/- 10.3 L/h, P =.567). Serum concentrations of follicle
      stimulating hormone, luteinizing hormone, and progesterone were not significantly
      affected by St John's wort dosing (P >.05). Breakthrough bleeding occurred in 2
      of 12 women in the control phase compared with 7 of 12 women in the St John's
      wort phase. The oral clearance of midazolam after St John's wort dosing was
      greater in women who had breakthrough bleeding (215.9 +/- 66.5 L/h) than in those
      who did not (97.5 +/- 37.2 L/h) (P =.005). CONCLUSION: St John's wort causes an
      induction of ethinyl estradiol-norethindrone metabolism consistent with increased
      CYP3A activity. Women taking oral contraceptive pills should be counseled to
      expect breakthrough bleeding and should consider adding a barrier method of
      contraception when consuming St Johns wort.

PMID- 14663456
TI  - Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6
      and 3A4 activity in normal volunteers.
AB  - Saw palmetto (Serenoa repens) is the most commonly used herbal preparation in the
      treatment of benign prostatic hyperplasia. The objective of this study was to
      determine whether a characterized saw palmetto product affects the activity of
      cytochrome P450 (CYP) 2D6 or 3A4 in healthy volunteers (6 men and 6 women). The
      probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4
      activity) were administered orally at baseline and again after exposure to saw
      palmetto (320-mg capsule once daily) for 14 days. Dextromethorphan metabolic
      ratios and alprazolam pharmacokinetics were determined at baseline and after saw
      palmetto treatment. The mean ratio of dextromethorphan to its metabolite was
      0.038 +/- 0.044 at baseline and 0.048 +/- 0.080 after 14 days of saw palmetto
      administration (P =.704, not significant [NS]), indicating a lack of effect on
      CYP2D6 activity. The area under the plasma alprazolam concentration versus time
      curve was 476 +/- 178 h. ng. mL(-1) at baseline and 479 +/- 125 h. ng. mL(-1)
      after saw palmetto treatment (P =.923, NS), indicating a lack of effect on CYP3A4
      activity. The elimination half-life of alprazolam was 11.4 +/- 3.1 hours at
      baseline and 11.6 +/- 2.7 hours after saw palmetto treatment (P =.770, NS), also
      indicating a lack of effect on CYP3A4 activity. Our results indicate that
      extracts of saw palmetto at generally recommended doses are unlikely to alter the
      disposition of coadministered medications primarily dependent on the CYP2D6 or
      CYP3A4 pathways for elimination. These conclusions must be weighed in the context
      of the study's limited assessments and regarded as only the initial investigation
      into the drug interaction potential of saw palmetto.

PMID- 14663457
TI  - Role of P-glycoprotein in the intestinal absorption and clinical effects of
      morphine.
AB  - INTRODUCTION: There is considerable and unexplained individual variability in the
      morphine dose-effect relationship. The efflux pump P-glycoprotein regulates brain
      access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein
      substrate in vitro, and P-glycoprotein affects morphine brain access and
      pharmacodynamics in animals. However, the role of P-glycoprotein in human
      morphine disposition and clinical effects is unknown. This investigation tested
      the hypothesis that plasma concentrations and clinical effects of oral and
      intravenous morphine are greater after inhibition of intestinal and brain P
      glycoprotein, with the P-glycoprotein inhibitor quinidine used as an in vivo
      probe. METHODS: Two randomized, double-blind, placebo-controlled, balanced
      crossover studies were conducted in normal healthy volunteers after institutional
      review board-approved informed consent was obtained. In the first protocol, pupil
      diameter was evaluated after intravenous morphine administration (0.15 mg/kg), 1
      hour after oral quinidine or placebo. In the second protocol, plasma morphine and
      glucuronide metabolite concentrations and pupil diameters were evaluated after
      oral morphine administration (30 mg), dosed 1 hour after oral quinidine (600 mg)
      or placebo. RESULTS: Quinidine had no effect on intravenous morphine effects
      (time to maximum miosis, maximum effect, or area under the curve [AUC] of miosis
      versus time). Quinidine increased the oral morphine maximum plasma concentration
      (31.8 +/- 14.9 ng/mL versus 16.9 +/- 7.4 ng/mL, P <.05) and AUC (65.1 +/- 21.5
      versus 40.8 ng. h. mL(-1) +/- 14 ng. h. mL(-1), P <.05) but had no effect on
      elimination rate. Plasma morphine glucuronide concentrations were unchanged;
      however, the morphine glucuronide/morphine ratios were diminished by quinidine.
      Differences in oral morphine miosis (AUC, 16.8 +/- 9.3 mm. h versus 10.8 +/- 6.5
      mm. h; P <.05) were commensurate with changes in plasma morphine concentration,
      and concentration-effect relationships were unchanged. Quinidine altered
      subjective self-assessments of oral but not intravenous morphine effects.
      DISCUSSION: Quinidine increased the absorption and plasma concentrations of oral
      morphine, suggesting that intestinal P-glycoprotein affected the absorption,
      bioavailability, and, hence, clinical effects of oral morphine. However,
      quinidine had no effect on morphine concentration-effect relationships,
      suggesting that if quinidine is an effective inhibitor of brain P-glycoprotein
      then P-glycoprotein did not appear to have a significant effect on brain access
      of morphine.

PMID- 14663458
TI  - Impaired 6-hydroxychlorzoxazone elimination in patients with kidney disease:
      Implication for cytochrome P450 2E1 pharmacogenetic studies.
AB  - OBJECTIVE: The purposes of this study were (1) to describe the disposition of
      chlorzoxazone and 6-hydroxychlorzoxazone in patients with kidney disease, (2) to
      develop a population pharmacokinetic model including covariates that may
      influence the pharmacokinetic variability of both compounds, and (3) to examine
      the effect of covariates on the chlorzoxazone metabolic ratio. METHODS: Twenty
      one subjects received a single oral dose of chlorzoxazone, 250 mg, and plasma and
      urine samples were collected for up to 120 hours. The impact of creatinine
      clearance (CL(cr)), age, and weight on chlorzoxazone and 6-hydroxychlorzoxazone
      clearance terms was assessed with NONMEM software (v.5, level 1.1; Globomax LLC,
      Hanover, Md) by use of a stepwise backward-elimination technique and the
      likelihood ratio test. RESULTS: A linear model with first-order absorption for
      chlorzoxazone and first-order formation for 6-hydroxychlorzoxazone simultaneously
      described the disposition of both compounds. Weight was a significant predictor
      of 6-hydroxychlorzoxazone formation clearance and other, unaccounted for
      clearance of chlorzoxazone, whereas CL(cr) was a significant predictor of 6
      hydroxychlorzoxazone renal clearance. No relationship between CL(cr) and
      formation clearance was observed. The 6-hydroxychlorzoxazone area under the
      plasma concentration-time curve was inversely related to CL(cr), even within the
      range of normal renal function, resulting in chlorzoxazone metabolic ratio values
      that were substantially higher in subjects with kidney disease. Both the
      experimental data and model-based Monte Carlo simulations revealed greatly
      increased chlorzoxazone metabolic ratio values when CL(cr) was low and weight was
      high. CONCLUSIONS: Although cytochrome P450 (CYP) 2E1 activity, as estimated by 6
      hydroxychlorzoxazone formation clearance, was not affected by kidney disease, the
      chlorzoxazone metabolic ratio was substantially elevated in these subjects. The
      results of this study show that the commonly used plasma-based chlorzoxazone
      metabolic ratio is dependent on renal function and, therefore, does not provide a
      reliable index of CYP2E1-mediated metabolism.

PMID- 14663459
TI  - Population pharmacokinetics of enfuvirtide in pediatric patients with human
      immunodeficiency virus: searching for exposure-response relationships.
AB  - OBJECTIVE: Our objective was to describe the population pharmacokinetics and
      pharmacodynamics of enfuvirtide acting on viral ribonucleic acid in children with
      human immunodeficiency virus 1. METHODS: A 1-compartment population
      pharmacokinetic model with first-order absorption and elimination was fit to
      subcutaneous and intravenous dose pharmacokinetic data from a 2-part study, as
      follows: an intensive-sample pharmacokinetic design (observed dose) (subcutaneous
      and intravenous, n = 12) followed by a sparse-sample design (unobserved dose)
      (subcutaneous, n = 15). The parameters of this model are clearance (CL), volume
      of distribution (V), absorption rate (k(a)), bioavailability (F), and both
      interindividual and residual variability. Plasma ribonucleic acid concentrations
      over time were used to build a population viral pharmacodynamics model with the
      following parameters: viral clearance (CL(v)), initial viral concentration
      (A(0)), duration (tau) and rate (R) of preinfected cell-based viral input after
      enfuvirtide was begun, and interindividual and residual variability. RESULTS: The
      mean population CL and V of enfuvirtide for a child with a mean body weight of
      21.3 kg were 1.42 L/h and 5.67 L, respectively. Patient weight affected CL and V.
      Volume appeared to differ between intensive and sparse sampling occasions, and
      this difference also affected the residual error variance. Time after the
      beginning of therapy did not significantly affect any pharmacokinetic parameter,
      supporting the absence of metabolic induction and inhibition. Although trends
      were present, no statistically significant relationship was seen between any
      pharmacokinetic-based individual enfuvirtide exposure measure and any virologic
      response measure. CONCLUSIONS: Regarding pharmacokinetics and pharmacodynamics,
      no statistically significant correlation between exposure measures and viral
      clearance was observed.

PMID- 14663460
TI  - Implication of cholesterol in cyclosporine pharmacodynamics in minimal change
      nephrotic syndrome.
AB  - BACKGROUND: High blood cholesterol concentrations in patients with minimal change
      nephrotic syndrome may affect cyclosporine (INN, ciclosporin) pharmacodynamics
      and its clinical efficacy, but few attempts have been carried out to disclose
      this problem. METHODS: We evaluated the cellular pharmacodynamics of cyclosporine
      in 24 patients with minimal change nephrotic syndrome. In vitro cyclosporine
      concentrations yielding 50% inhibition (IC(50)) of blastogenesis of peripheral
      blood mononuclear cells (PBMCs) stimulated with concanavalin A were calculated.
      The relationships between the IC(50) values and laboratory data including serum
      total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density
      lipoprotein (HDL) cholesterol concentrations were examined. Clinical cyclosporine
      efficacy was assessed by a decreasing rate (percentage) of urinary protein 1 week
      after cyclosporine therapy. Percentages of LDL receptor-positive or CD3-positive
      PBMCs were evaluated with flow cytometry in 7 patients and 15 healthy subjects.
      RESULTS: The cyclosporine IC(50) values negatively correlated with the clinical
      cyclosporine efficacy assessed by a decreasing rate of urinary protein (r = 
      0.708, P =.0006). Cyclosporine IC(50) values significantly correlated with either
      serum total cholesterol (r = 0.681, P =.0003) or LDL cholesterol (r = 0.751, P
      =.0034) concentrations. Furthermore, serum total or LDL cholesterol levels
      significantly correlated negatively with clinical cyclosporine efficacy (r = 
      0.613, P =.0057, and r = -0.773, P =.0399, respectively). In 7 patients, serum
      total and LDL cholesterol concentrations were significantly higher than those of
      15 healthy subjects (P <.005), whereas the percentages of LDL receptor-expressing
      cells in CD3-enriched PBMCs were not significantly different between these
      patients and healthy subjects. In addition, the cyclosporine IC(50) values and
      the percentages of LDL receptor-expressing PBMCs did not negatively correlate in
      either the patients or the healthy subjects. CONCLUSIONS: The data raised the
      possibility that hypercholesterolemia in patients with minimal change nephrotic
      syndrome attenuates cellular and clinical cyclosporine pharmacodynamics. Down
      regulation of LDL receptor in T cells was not observed in these patients, and
      individual deviation of PBMC response to cyclosporine does not appear to be
      related to the difference of LDL receptor-positive cell numbers.

PMID- 14663461
TI  - Severe neutropenia among healthy volunteers given rifabutin in clinical trials.

PMID- 14663465
TI  - What's hot in the prostate?

PMID- 14663466
TI  - Patterns of protease production during prostate cancer progression: proteomic
      evidence for cascades in a transgenic model.
AB  - Extracellular proteases are recognized as critical factors in the progression of
      a number of carcinomas, including prostate cancer. Matrix metalloproteases (MMP)
      are important in processes of tumor growth, invasion and dissemination, but other
      classes of proteases, such as serine and cysteine proteases, also contribute. We
      utilized the TRAMP model for prostate cancer to elucidate proteases involved in
      prostate cancer progression. General proteomic analysis was performed on normal
      murine prostate, early TRAMP tumors and advanced TRAMP tumors, as well as normal
      and involved lymph nodes. Zymography and antigenic analyses revealed increased
      expression of mainly pro-MMP in early TRAMP tumors but substantial elaboration of
      activated MMP only in late TRAMP tumors. Progressive increase in cysteine, serine
      and certain membrane-bound proteases from normal to early to advanced prostate
      tumors, was also seen. Our results implicate pericellular proteases as initiators
      of major proteolytic cascades during tumor progression and suggest targets for
      maximal therapeutic effect.

PMID- 14663467
TI  - p53 Immunostaining guided laser capture microdissection (p53-LCM) defines the
      presence of p53 gene mutations in focal regions of primary prostate cancer
      positive for p53 protein.
AB  - OBJECTIVES: A wide range of p53 mutations (5-65%), detected by various methods,
      has been reported in primary prostate cancers (CaP). IHC staining of radical
      prostatectomy specimens shows marked heterogeneity of focally distributed p53
      positive cells. However, a significant relationship between the focal staining of
      p53 and cancer recurrence after radical prostatectomy has been noted. Increased
      frequency of p53 mutations has been generally observed in advanced stage CaP and
      metastatic prostate cancer cell lines. The significance of focal p53
      immunostaining in primary CaP remains uncertain with respect to the p53 gene
      mutation or tumor progression. The goal of this study was to evaluate p53 gene
      mutations in focal regions of primary prostate cancers positive by p53
      immunostaining. METHODS: Whole-mount prostates from men with clinically organ
      confined prostate cancer were immunostained for p53 protein. Laser capture
      microdissection (LCM) was used to harvest p53 positive cells from areas of tumor
      and prostatic intraepithelial neoplasia and benign gland. DNA from microdissected
      cells were amplified for p53 exons 5-8 by polymerase chain reaction (PCR) and
      analyzed for mutations by single strand conformation polymorphism and DNA
      sequencing. Mutation analysis of the p53 gene exons 5-8 was performed in the p53
      immunostaining positive focal regions (1+ to 4+) of whole-mount prostate sections
      from 16 patients. RESULTS: Of 16 patients with p53 IHC positive tumors, 11 (69%)
      had p53 gene mutations as determined by DNA sequence analysis. However, randomly
      microdissected tumor cells from 4 of 18 patients (22%) negative for p53 IHC also
      demonstrated mutations in the p53 gene. A significant fraction of prostate tumors
      with focally positive immunostaining for p53 have been confirmed to contain
      mutations in the p53 gene. CONCLUSIONS: p53 immunostaining guided LCM combined
      with DNA-based analyses emphasizes the presence of focal p53 mutations in primary
      prostate cancers and underscores the significance of previous observations
      showing a correlation between focal p53 immunostaining in primary CaP and cancer
      recurrence after radical prostatectomy.

PMID- 14663468
TI  - Immune function, mitogenicity, and angiogenic growth factor concentrations in
      lean and obese rodent sera: implications in obesity-related prostate tumor
      biology.
AB  - Some studies suggest that several tumors have a greater incidence in those
      patients with a high fat diet, such as colon, breast, and prostate. However, we
      wanted to determine the effects of obesity alone, independent of diet, on the
      progression of prostate tumor growth. Using a genetic model of obese and lean
      Zucker rats, we wanted to demonstrate any sera differences in the concentration
      of basic fibroblast growth factor (FGF-2) and vascular endothelial cell growth
      factor (VEGF), two important factors involved in the growth and progression of
      prostate cancer. We also wanted to investigate if there were any differences in
      immune function between the two sera, which could also account for uninhibited
      tumor growth, as well as differences in mitogenic stimulation. Female Zucker rat
      obese and lean sera were analyzed using ELISA assays for FGF-2, VEGF, and
      macrophage inflammatory protein-1 alpha (MIP-1a), as a measure of macrophage
      function. In addition, the sera of lean and obese sera were plated on wells
      growing LNCaP prostate cancer cells to determine differences in mitogenicity. We
      found a greater concentration of FGF-2 in the sera from obese Zucker rats
      compared to lean Zucker rats: 6.32+/-0.56 vs 3.48+/-0.34 pg/ml, respectively,
      P<0.05). We also demonstrated a greater concentration of VEGF in obese rat sera
      compared to lean sera: 54.4+/-4.1 vs 38.0+/-2.9 pg/mL, respectively, P<0.05). We
      detected a trend in mitogenic stimulation among LNCaP cells along the higher
      concentrations of the dose-response curve (0.72+/-0.06 vs 0.51+/-0.5). However,
      this was not statistically significant. In addition, we did not find a
      significant difference in MIP-1a macrophage activity levels between sera. To
      conclude, we speculate that the greater concentrations of VEGF and FGF-2 in the
      sera of obese rodents vs lean rodents may account for some of the differences
      seen in obesity-related tumor growth seen in the human condition. However, the
      lack of any sera differences of immune function, as measured by macrophage
      activity, as well as no significant differences on mitogenic proliferation on
      LNCaP prostate cancer cells, suggests that other mechanisms may exist to explain
      differences seen in obesity-related prostate tumor biology.

PMID- 14663469
TI  - Prostate cancer transfection by acoustic energy using pEGFP-N1 as reporter gene
      in the solid Dunning R-3327-MatLu tumor.
AB  - BACKGROUND: Gene therapy is expected to play a major role in medical treatment in
      the future. Several different methods for DNA transfection exist. We evaluated
      the efficacy and effects of transfection by acoustic energy in a standardized
      prostate cancer model. METHODS: Subcutaneous implantation of Dunning tumors was
      followed by injection of pEGFP-DNA plasmid. Tumors were treated by acoustic
      energy with different parameter settings and the transfection rate was assessed
      by FACScan. RESULTS: Standardized experimental conditions resulted in minor
      intragroup deviations. Intratumoral injection resulted in a transfection rate of
      0.3% (control group). The statistically significant increase of 4.6% in cell
      transfection rate was gained by applying acoustic energy. CONCLUSIONS: DNA
      transfection of solid tumors can be mediated by the application of acoustic
      energy. Achieved transfection rates are encouraging and imply therapeutical
      levels. Prodrug activation or suicide gene therapy are possible fields of
      investigation in the treatment of prostate cancer.

PMID- 14663470
TI  - Androgen receptor antigen density and S-phase fraction in prostate cancer: a
      pilot study.
AB  - PURPOSE: To determine whether quantitative flow cytometric androgen receptor
      density expression (MFC ratio) in prostate cancer was associated with S-phase
      fraction. METHODS: Flow cytometry was performed to determine DNA aneuploidy, S
      phase fraction, percentage of androgen receptor (AR)-positive cells, and MFC
      ratio in prostate cancer patients. RESULTS: MFC ratio showed distinct clustering.
      Eight patients had a low MFC ratio of 1.78-2.74, while 10 patients had high MFC
      ratios between 4.99 and 6.48. The S-phase fraction had average values of 11.05 vs
      4.92 in tumors with high vs low MFC ratio (P<0.01). CONCLUSION: S-phase fraction
      was significantly higher in tumors with high AR density.

PMID- 14663471
TI  - Modified citrus pectin (MCP) increases the prostate-specific antigen doubling
      time in men with prostate cancer: a phase II pilot study.
AB  - This trial investigated the tolerability and effect of modified citrus pectin
      (Pecta-Sol) in 13 men with prostate cancer and biochemical prostate-specific
      antigen (PSA) failure after localized treatment, that is, radical prostatectomy,
      radiation, or cryosurgery. A total of 13 men were evaluated for tolerability and
      10 for efficacy. Changes in the prostate-specific antigen doubling time (PSADT)
      of the 10 men were the primary end point in the study. We found that the PSADT
      increased (P-value<0.05) in seven (70%) of 10 men after taking MCP for 12 months
      compared to before taking MCP. This study suggests that MCP may lengthen the
      PSADT in men with recurrent prostate cancer.

PMID- 14663472
TI  - Is low-grade prostatic intraepithelial neoplasia a risk factor for cancer?
AB  - INTRODUCTION: High-grade prostatic intraepithelial neoplasia (HGPIN) is generally
      accepted to be a precursor lesion of prostate cancer. The likely outcome of
      isolated low-grade PIN (LGPIN) lesions in prostate biopsies remains unclear. A
      follow-up study of 106 patients with LGPIN- and HGPIN lesions was performed.
      MATERIALS AND METHODS: In a 2-y period, 207 men were diagnosed with isolated PIN
      on standard systematic sextant biopsy of the prostate. In total, 104 patients had
      LGPIN and 103 had HGPIN. No patients had ever received androgen deprivation
      therapy, chemotherapy or radiation therapy. In all, 106 patients who underwent
      repeat second or third sextant biopsies were analysed in the study; 30% of these
      patients received a selenium-vitamin E supplement for at least 6 months. RESULTS:
      In total, 43 had LGPIN and 63 HGPIN on the first biopsy. The mean age was 63.5 y
      (range 46-77) in the LGPIN group and 64.9 y in the HGPIN group. The mean total
      PSA was 6.96 ng/ml (range 0.59-34.13) in the LGPIN group and 8.44 ng/ml (range
      0.59-35.3) in the HGPIN group. In the LGPIN group, 30% of the patients had cancer
      in at least one of the repeat biopsy cores. In the HGPIN group, 27% had cancer in
      at least one of the repeat biopsy cores. The mean total PSA of patients who had
      cancer in repeat biopsies with LGPIN was 7.84 ng/ml (range 2.92-34.13). The mean
      total PSA of the patients who had cancer in repeat biopsy in the HGPIN was 6.73
      ng/ml (range 0.56-25). There was no significant difference in PSA and
      pathological stage between those patients who did and those who did not receive
      selenium-vitamin E supplements. CONCLUSIONS: These data are intriguing since the
      risk of finding prostate carcinoma on repeat sextant biopsy in the LGPIN group is
      30%. This is higher than commonly reported. The importance of recognising and re
      biopsying HGPIN was confirmed. If chemoprevention could be shown to be effective,
      it might be beneficial not only in HGPIN but also in LGPIN. The possible activity
      of chemopreventive agents and their combination with iso-flavonoids needs further
      investigation.

PMID- 14663473
TI  - Transrectal periprostatic lidocaine injection anesthesia for transrectal prostate
      biopsy: a prospective study.
AB  - Transrectal ultrasound (TRUS)-guided biopsy remains the mainstay of the diagnosis
      of prostate cancer. Although this diagnostic method is a safe procedure and well
      tolerated by most patients a significant number of patients report discomfort and
      pain during prostate biopsy. In order to define the best method of anesthesia,
      many studies, in which different methods were compared, have been performed. To
      determine the effectiveness of local injection anesthesia in TRUS-guided prostate
      biopsy, we designed and performed this prospective study in order to evaluate the
      utility of periprostatic nerve block for pain management. A total of 100 patients
      who had elevated total prostate-specific antigen (tPSA) and/or abnormal digital
      rectal examination (DRE) were included in this study. Half of the patients
      received periprostatic injection anesthesia (group I) and the remaining half
      received placebo (group II). Patients received 10 cm3 (5 cm3 each side) 1%
      lidocaine injected into the periprostatic nerve plexus under transrectal
      ultrasonic guidance. Pain during biopsy was assessed using a 10-point modified
      visual analog scale (VAS). In groups I and II, mean patient age was 66.8+2.5 and
      65.6+11.5 y, mean tPSA was 7.87+/-3.6 and 11.3+/-1.7 ng/ml, mean biopsy duration
      was 6.5+/-2.5 and 6.6+/-2.2 min and mean pain score during TRUS-guided biopsy was
      1.46+/-2.2 and 4.5+/-2.1, respectively. No statistically significant difference
      was observed with respect to age, tPSA and mean biopsy duration between these
      groups. Mean pain VAS score was statistically or significantly better (P=0.0001)
      in the lidocaine injection group (group I), and furthermore no patient had a VAS
      pain score > or =5 in this group. Only minor and transient complications occurred
      in both groups. This study reinforces the usage of periprostatic nerve block as a
      standard method of pain management during TRUS-guided prostate biopsy, because it
      is simple, safe, uncostly and significantly effective without requiring
      additional time.

PMID- 14663474
TI  - A comparison of the efficacy and tolerability of tamsulosin and finasteride in
      patients with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia.
AB  - In this multicentre, double-blind study, patients with LUTS/BPH were randomised
      to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once
      daily (n=199). Double-blind treatment was continued for another 26 weeks (total
      treatment duration: 1 y). The primary efficacy parameter was the difference in
      mean change in total Symptom Problem Index (SPI) from baseline to end point at
      week-26 in the intention-to-treat (ITT) and per protocol (PP) populations.
      Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%)
      compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and
      P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more
      bothersome storage symptoms) and flow more quickly than finasteride. The
      difference was statistically significant for the SPI from week-1 (reduction,
      respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1
      (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments
      were well tolerated with a comparable incidence of adverse events, including
      urinary retention.

PMID- 14663476
TI  - To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the
      regulation of apoptosis.
AB  - During their lifetime, cells encounter many life or death situations that
      challenge their very own existence. Their survival depends on the interplay
      within a complex yet precisely orchestrated network of proteins. The Rel/NF
      kappaB signaling pathway and the transcription factors that it activates have
      emerged as critical regulators of the apoptotic response. These proteins are best
      known for the key roles that they play in normal immune and inflammatory
      responses, but they are also implicated in the control of cell proliferation,
      differentiation, apoptosis and oncogenesis. In recent years, there has been
      remarkable progress in understanding the pathways that activate the Rel/NF-kappaB
      factors and their role in the cell's decision to either fight or surrender to
      apoptotic challenge. Whereas NF-kappaB is most commonly involved in suppressing
      apoptosis by transactivating the expression of antiapoptotic genes, it can
      promote programmed cell death in response to certain death-inducing signals and
      in certain cell types. This review surveys our current understanding of the role
      of NF-kappaB in the apoptotic response and focuses on many developments since
      this topic was last reviewed in Oncogene 4 years ago. These recent findings shed
      new light on the activity of NF-kappaB as a critical regulator of apoptosis in
      the immune, hepatic, epidermal and nervous systems, on the mechanisms through
      which it operates and on its role in tissue development, homoeostasis and cancer.

PMID- 14663477
TI  - PI3K/Akt and apoptosis: size matters.
AB  - Recent research has examined Akt and Akt-related serine-threonine kinases in
      signaling cascades that regulate cell survival and are important in the
      pathogenesis of degenerative diseases and in cancer. We seek to recapitulate the
      research that has helped to define the current understanding of the role of the
      Akt pathway under normal and pathologic conditions, also in view of genetic
      models of Akt function. In particular, we will evaluate the mechanisms of Akt
      regulation and the role of Akt substrates in Akt-dependent biologic responses in
      the decisions of cell death and cell survival. Here, we hope to establish the
      mechanisms of apoptosis suppression by Akt kinase as a framework for a more
      general understanding of growth factor-dependent regulation of cell survival.

PMID- 14663478
TI  - The dark side of Ras: regulation of apoptosis.
AB  - Mutational activation of Ras promotes oncogenesis by disrupting a multitude of
      normal cellular processes. Perhaps, best characterized and understood are the
      mechanisms by which oncogenic Ras promotes deregulated cell cycle progression and
      uncontrolled cellular proliferation. However, it is now clear that oncogenic Ras
      can also deregulate processes that control apoptosis. In light of the diversity
      of downstream effector targets known to facilitate Ras function, it is perhaps
      not surprising that Ras regulation of cell survival is complex, involving the
      balance and interplay of multiple signaling networks. While our understanding of
      these events is still far from complete, and is complicated by cell type and
      signaling context differences, several important mechanisms have begun to emerge.
      We review the role and mechanism of specific effectors in regulating the
      antiapoptotic (Raf, phosphatidylinositol 3-kinase and Tiam1) and apoptotic (Nore1
      and RASSF1) actions of oncogenic Ras, and discuss the possibility that the
      effector actions of p120RasGAP make a significant contribution to Ras regulation
      of apoptotic events.

PMID- 14663479
TI  - Myc pathways provoking cell suicide and cancer.
AB  - A paradox for the cancer biology field has been the revelation that oncogenes,
      once thought to simply provide advantages to a cancer cell, actually put it at
      dire risk of cell suicide. Myc is the quintessential oncogene in this respect, as
      in normal cells it is required for cell cycle traverse, whereas in cancers it is
      overexpressed and functions as the angiogenic switch. Nonetheless, Myc
      overexpression kills normal cells dead in their tracks. Here we review Myc
      induced pathways that contribute to the apoptotic response. Molecular analysis of
      Myc-induced tumors has established that some of these apoptotic pathways are
      essential checkpoints that guard the cell from cancer, as they are selectively
      bypassed during tumorigenesis. The precise mechanism(s) by which Myc targets
      these pathways are largely unresolved, but we propose that they involve crosstalk
      and feedback regulatory loops between arbiters of cell death.

PMID- 14663480
TI  - Apoptotic cues from the extracellular matrix: regulators of angiogenesis.
AB  - A variety of factors cooperate to regulate neovessel formation and persistence.
      Proangiogenic growth factors have remained an area of intense interest due to
      their capacity to promote endothelial cell (EC) proliferation and to initiate the
      angiogenic program. These growth factors are associated with increased cell
      survival, yet paradoxically, angiogenic ECs are more susceptible to apoptosis
      than quiescent ECs. Survival is regulated by cooperation between growth factor
      receptors and integrins, which are in turn governed by the composition of the
      local extracellular matrix (ECM). Integrin-mediated signaling is altered or
      disrupted by the presence of soluble, rather than matrix-bound ligands, thus
      providing a means by which ECM remodeling can influence both integrin- and growth
      factor-mediated events. Ultimately, the collaboration of these factors determines
      whether ECs survive or die, thereby regulating neovascularization.

PMID- 14663481
TI  - Control of apoptosis by p53.
AB  - The p53 tumor suppressor acts to integrate multiple stress signals into a series
      of diverse antiproliferative responses. One of the most important p53 functions
      is its ability to activate apoptosis, and disruption of this process can promote
      tumor progression and chemoresistance. p53 apparently promotes apoptosis through
      transcription-dependent and -independent mechanisms that act in concert to ensure
      that the cell death program proceeds efficiently. Moreover, the apoptotic
      activity of p53 is tightly controlled, and is influenced by a series of
      quantitative and qualitative events that influence the outcome of p53 activation.
      Interestingly, other p53 family members can also promote apoptosis, either in
      parallel or in concert with p53. Although incomplete, our current understanding
      of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor
      network controlled by different signals, environmental factors, and cell type.
      Understanding this network in more detail will provide insights into cancer and
      other diseases, and will identify strategies to improve their therapeutic
      treatment.

PMID- 14663482
TI  - Heat-shock proteins as regulators of apoptosis.
AB  - Heat-shock proteins are produced in response to different types of stress
      conditions making cells resistant to stress-induced cell damage. Under normal
      conditions, heat-shock proteins play numerous roles in cell function, including
      modulating protein activity by changing protein conformation, promoting
      multiprotein complex assembly/disassembly, regulating protein degradation within
      the proteasome pathway, facilitating protein translocation across organellar
      membranes, and ensuring proper folding of nascent polypeptide chains during
      protein translation. When cells are stressed, a common response is to undergo
      cell death by one of two pathways, either 'necrosis' or 'apoptosis'. Recently,
      both routes to cell death have been revealed to share similar mechanisms, with
      heat-shock proteins and their cofactors responsible for inhibiting both apoptotic
      and necrotic pathways. We therefore briefly summarize recent reports showing
      molecular evidence of cell death regulation by heat-shock proteins and their
      cochaperones.

PMID- 14663483
TI  - Role of PML and the PML-nuclear body in the control of programmed cell death.
AB  - PML is a tumor suppressor implicated in leukemia and cancer pathogenesis. PML
      epitomizes a multiprotein nuclear structure, the PML-nuclear body (PML-NB), whose
      proper formation and function depends on PML. Studies in knockout (KO) mice and
      cells unraveled an essential pleiotropic role for PML in multiple p53-dependent
      and -independent apoptotic pathways. As a result, Pml(-/-) mice and cells are
      protected from apoptosis triggered by a number of stimuli such as ionizing
      radiation, interferon, ceramide, Fas and TNF. It is becoming apparent that PML
      and the PML-NB act as molecular hubs for the induction and/or reinforcement of
      programmed cell death through a selective and dynamic regulation of proapoptotic
      transcriptional events. In addition, recent observations propose a role for PML
      in checkpoint responses upon DNA damage. Moreover, PML and the PML-NB have also
      been implicated in the control of genomic stability and DNA repair. Here, we will
      discuss the molecular mechanisms by which PML regulates these processes and the
      implication of these findings for cancer pathogenesis and therapy.

PMID- 14663484
TI  - Retinoid targets for apoptosis induction.
AB  - Certain synthetic retinoid-related molecules induce apoptosis in cancer cells
      through a novel mechanism of retinoid action that is independent of the nuclear
      retinoid receptors. These compounds target protein kinases and protein
      phosphatases to trigger signal transduction pathways that lead to apoptosis.
      Whereas retinoid agonists such as CD437 activate stress kinases via inhibition of
      the phosphatase MKP-1, the retinoid antagonist MX781 inhibits the survival kinase
      IKK. These retinoid-mediated signaling pathways converge at the mitochondria,
      where they cause the release of cytochrome c and subsequent Apaf-1-dependent
      activation of caspases. Identification of the retinoid targets that mediate their
      apoptotic activity will enhance our understanding of the mechanism of this novel
      retinoid action, to allow appropriate optimization of currently available
      compounds to advance into the clinic as novel anticancer agents.

PMID- 14663485
TI  - Mechanisms of apoptosis induction by nucleoside analogs.
AB  - Nucleoside analogs are structurally, metabolically, and pharmacodynamically
      related agents that nevertheless have diverse biological actions and therapeutic
      consequences. This class of agents affects the structural integrity of DNA,
      generally after incorporation during replication or DNA excision repair
      synthesis, leading to stalled replication forks and chain termination. The DNA
      damage sensors ATM, ATR and DNA-PK recognize these events. These and other
      protein kinases activate checkpoint pathways that arrest cell cycle progression,
      and also signal for DNA repair. In addition, if these survival mechanisms are
      overwhelmed by the damage caused, a third function of these sensors is to
      activate signaling pathways that initiate apoptotic processes. A review of the
      spectrum of responses that are activated by clinically relevant nucleoside
      analogs begins to provide a mechanistic basis for diverse outcomes in cell
      viability. Such information, when coupled with an understanding of the intrinsic
      apoptotic potential of a tumor cell type may provide a rational basis for the
      design of therapeutic strategies.

PMID- 14663486
TI  - Microtubule-targeted anticancer agents and apoptosis.
AB  - Over the past decade, significant progress has been made in our understanding of
      the biology of microtubule (MT) assembly into the mitotic spindle during mitosis
      and the molecular signaling and execution of the various pathways to apoptosis.
      In the same period, the microtubule-targeted tubulin-polymerizing agents (MTPAs),
      notably paclitaxel and taxotere, have come to occupy a central role in the
      treatment of a variety of human epithelial cancers. Following their binding to B
      tubulin, MTPAs inhibit MT dynamic instability, cell cycle G2/M phase transition
      and mitotic arrest of cancer cells. MTPA-induced anti-MT and cell cycle effects
      trigger the molecular signaling for the mitochondrial pathway of apoptosis. This
      triggering is orchestrated through different molecular links and determined by
      the threshold for apoptosis that is set and controlled diversely in various
      cancer types. The complexity and regulatory potential of the links and the
      apoptosis threshold are integral to the transformed biology of the cancer cell.
      The emerging understanding of this biology and how it is influenced by treatment
      with MTPAs has highlighted novel strategies to further enhance the antitumor
      activity and overcome resistance to MTPA-induced apoptosis in cancer cells.

PMID- 14663487
TI  - Antisense oligonucleotide-based therapeutics for cancer.
AB  - There has been steady progress in antisense technology over the past 14 years. We
      now have a far better appreciation of the attributes and limitations of the
      technology. Antisense oligonucleotides have been used to selectively inhibit
      thousands of genes in mammalian cells, hundreds, if not thousands, of genes in
      rodents and other species and multiple genes in humans. There are over 20
      antisense drugs currently in clinical trials, several of which are showing
      promising results. Like any other class of drugs in development, there will
      continue to be successes and failures in the clinic. Despite some disappointments
      with the technology, it appears to be a valid platform for both drug discovery
      and as an experimental tool for functionalizing genes. Advances in the medicinal
      chemistry and formulation of antisense oligonucleotides will further enhance
      their therapeutic and commercial potential.

PMID- 14663488
TI  - Monoclonal antibody therapeutics and apoptosis.
AB  - The potential for disease-specific targeting and low toxicity profiles have made
      monoclonal antibodies attractive therapeutic drug candidates. Antibody-mediated
      target cell killing is frequently associated with immune effector mechanisms such
      as antibody-directed cellular cytotoxicity, but they can also be induced by
      apoptotic processes. Antibody-directed mechanisms, including antigen
      crosslinking, activation of death receptors, and blockade of ligand-receptor
      growth or survival pathways, can elicit the induction of apoptosis in targeted
      cells. Depending on their mechanism of action, monoclonal antibodies can induce
      targeted cell-specific killing alone or can enhance target cell susceptibility to
      chemo- or radiotherapeutics by effecting the modulation of antiapoptotic
      pathways. This review will focus on the mechanisms by which antibodies are
      capable of eliciting programmed cell death either directly or indirectly within
      tumor cells.

PMID- 14663490
TI  - Sorting out the nuclear envelope from the endoplasmic reticulum.
AB  - Although the interphase nuclear envelope is continuous with the endoplasmic
      reticulum, it is distinct from the endoplasmic reticulum in both form and
      composition. In metazoans, the nuclear envelope breaks down during mitosis and is
      thought to be completely reabsorbed by the endoplasmic reticulum. How these near
      neighbours are sorted out at the end of mitosis is an interesting mystery.

PMID- 14663491
TI  - Analysis of the anorectic efficacy of HMR1426 in rodents and its effects on
      gastric emptying in rats.
AB  - OBJECTIVES: Pharmacodynamics of HMR1426 in rodents. SUBJECTS: Male and female
      rats and male mice. MEASUREMENTS: 24 h feed consumption was measured. From the
      time curves IC(50) values of HMR1426 were calculated. Microanalysis of feeding
      behavior was determined. Macronutrient preference was measured, by offering rats
      three different diets. Gastric emptying was measured after liquid gastric loads
      or solid meals. In rats with gastric cannulas, milk consumption was measured with
      closed or open cannulas. Diabetes-related parameters and thyroid hormones were
      measured. RESULTS: HMR1426 inhibited feed consumption dose-dependently in
      rodents. Microstructural analysis of feeding after HMR1426 differed from central
      acting anorectics. HMR1426 inhibited consumption of fat- and carbohydrate
      enriched diets. Gastric emptying was dose- and time-dependently delayed. Gastric
      emptying correlated with the time course of the anorectic effect. In sham-fed
      rats, HMR1426 had no anorectic effect with open cannulas. Anorectic effect
      occurred with closed cannulas. We proved that HMR1426 is not a CCK(A) agonist.
      CONCLUSION: The correlation between anorectic properties of HMR1426 and gastric
      emptying suggests that gastric emptying may cause the anorectic properties of
      HMR1426. The differences in microstructural feeding behavior between HMR1426 and
      centrally active anorectics makes it unlikely that HMR1426 acts via the CNS.
      Evidence for a peripheral mode of action is derived from sham-fed rats with open
      gastric fistula. When the milk fed was drained, HMR1426 was ineffective. HMR1426
      is not a CCK(A) agonist. The molecular action of HMR1426 causing gastric emptying
      and its anorectic properties are under investigation.

PMID- 14663492
TI  - Influence of bacterial strains isolated from lead-polluted soil and their
      interactions with arbuscular mycorrhizae on the growth of Trifolium pratense L.
      under lead toxicity.
AB  - We isolated two bacterial strains from an experimentally lead (Pb)-polluted soil
      in Hungary, 10 years after soil contamination. These strains represented the two
      most abundant cultivable bacterial groups in such soil, and we tested their
      influence on Trifolium pratense L. growth and on the functioning of native
      mycorrhizal fungi under Pb toxicity in a second Pb-spiked soil. Our results
      showed that bacterial strain A enhanced plant growth, nitrogen and phosphorus
      accumulations, nodule formation, and mycorrhizal infection, demonstrating its
      plant-growth-promoting activity. In addition, strain A decreased the amount of Pb
      absorbed by plants, when expressed on a root weight basis, because of increased
      root biomass due to the production of indoleacetic acid. The positive effect of
      strain A was not only evident after a single inoculation but also in dual
      inoculation with arbuscular mycorrhizal fungi. Strain A also exhibited higher
      tolerance than strain B when cultivated under increasing Pb levels in the spiked
      soil. Molecular identification unambiguously placed strain A within the genus
      Brevibacillus. We showed that it is important to select the most tolerant and
      efficient bacterial strain for co-inoculation with arbuscular mycorrhizal fungi
      to promote effective symbiosis and thus stimulate plant growth under adverse
      environmental conditions, such as heavy-metal contamination.

PMID- 14663493
TI  - Culture-independent phylogenetic analysis of the faecal flora of the rat.
AB  - The dominant faecal flora of the rat was determined using randomly cloned 16S
      rDNA comparative sequence analysis. A total of 109 near full-length 16S rDNA
      clones were sequenced, representing 69 unique 16S rRNA phylotypes or operational
      taxonomic units (OTUs). Estimates of species richness indicated that
      approximately 338 species were present in the faeces, suggesting that only 20% of
      species were identified. Only two of 39 Gram-negative clones aligned with
      previously cultured species, the remainder fell into a separate lineage within
      the Bacteroides-Cytophaga phylum. Several clones within this new group were
      related to 16S rDNA sequences previously identified from mouse faeces.
      Lactobacilli were the most abundant Gram-positive species, representing 23% of
      the total clones but only 7% of OTUs. The remaining Gram-positive clones were
      distributed among the Clostridium coccoides group (9%), the Clostridium leptum
      subgroup (18%), and throughout the low GC Gram-positive bacteria (13%). The
      majority of OTUs (63/69 or 91%) were less than 97% homologous to previously
      cultured bacteria. Faecal samples were also cultured using a variety of anaerobic
      media. With the exception of the lactobacilli, the cultured isolates demonstrated
      low species diversity and poorly reflected the population, as defined through
      comparative sequence analysis.

PMID- 14663494
TI  - Methanotrophic diversity in high arctic wetlands on the islands of Svalbard
      (Norway)--denaturing gradient gel electrophoresis analysis of soil DNA and
      enrichment cultures.
AB  - The methanotrophic community in arctic soil from the islands of Svalbard, Norway
      (78 degrees N) was analysed by combining group-specific PCR with PCR of the
      highly variable V3 region of the 16S rRNA gene and then by denaturing gradient
      gel electrophoresis (DGGE). Selected bands were sequenced for identification. The
      analyses were performed with DNA extracted directly from soil and from enrichment
      cultures at 10 and 20 degrees C. The two genera Methylobacter and Methylosinus
      were found in all localities studied. The DGGE band patterns were simple, and DNA
      fragments with single base differences were separated. The arctic tundra is a
      potential source of extensive methane emission due to climatic warming because of
      its large reservoirs of stored organic carbon. Higher temperatures due to
      climatic warming can cause increased methane production, and the abundance and
      activity of methane-oxidizing bacteria in the arctic soil may be important
      regulators for methane emission to the atmosphere.

PMID- 14663495
TI  - Putative virulence factors are released in association with membrane vesicles
      from Burkholderia cepacia.
AB  - Like many other Gram-negative bacteria, Burkholderia cepacia naturally releases
      membrane vesicles (n-MVs) during normal growth. Through filtration and
      differential centrifugation, n-MVs from clinical isolates of the IIIa and V
      genomovars were isolated and their characteristics compared. Electron microscopy
      revealed that they were spherical, 30-220 nm in diameter, and bilayered.
      Virulence factors thought to play a role in pathogenicity (e.g., lipase,
      phospholipase-N, and protease, including a metalloprotease) were found associated
      with n-MVs, while peptidoglycan zymogram analysis also revealed 26, 28, 36, and
      66 kDa peptidoglycan-degrading enzymes. n-MVs were often contaminated with
      flagella and pili when isolated by traditional methods, and a new strategy using
      a linear isopycnic sucrose gradient was utilized. For better characterization,
      this was applied to a representative genomovar IIIa strain (C5424) and showed
      that n-MVs consisted of a subset of specific outer membrane and periplasmic
      proteins as well as lipopoly saccharide possessing only a putative minor O-side
      chain polymer. This finding suggests that certain components are selected by B.
      cepacia during n-MV formation, and since some are putative virulence factors,
      this property could help deliver the factors to tissue, thereby aiding infection.

PMID- 14663496
TI  - A metalloproteinase extracellularly released by Crithidia deanei.
AB  - Actively motile cells from a cured strain of Crithidia deanei released proteins
      in phosphate buffer (pH 7.4). The molecular mass of the released polypeptides,
      which included some proteinases, ranged from 19 to 116 kDa. One of the major
      protein bands was purified to homogeneity by a combination of anion-exchange and
      gel filtration chromatographs. The apparent molecular mass of this protein was
      estimated to be 62 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The incorporation of gelatin into SDS-PAGE showed
      that the purified protein presented proteolytic activity in a position
      corresponding to a molecular mass of 60 kDa. The enzyme was optimally active at
      37 degrees C and pH 6.0 and showed 25% of residual activity at 28 degrees C for
      30 min. The proteinase was inhibited by 1,10-phenanthroline and EDTA, showing
      that it belonged to the metalloproteinase class. A polyclonal antibody to the
      leishmanial gp63 reacted strongly with the released C. deanei protease. After
      Triton X-114 extraction, an enzyme similar to the purified metalloproteinase was
      detected in aqueous and detergent-rich phases. The detection of an extracellular
      metalloproteinase produced by C. deanei and some other Crithidia species suggests
      a potential role of this released enzyme in substrate degradation that may be
      relevant to the survival of trypanosomatids in the host.

PMID- 14663497
TI  - Characterization of Neisseria meningitidis strains isolated from invasive
      meningococcal disease cases in Canada in 2001.
AB  - With the recent introduction of polysaccharide-protein conjugated vaccines for
      the control of serogroup C meningococcal disease and the emergence of different
      variants of serogroup C meningococci, it is likely the epidemiology of
      meningococcal disease in many countries may be affected. We have therefore
      analysed and reported the characteristics of Neisseria meningitidis strains
      collected in 2001 from the Canadian surveillance program on invasive
      meningococcal disease. Only strains collected from normally sterile clinical
      sites of patients were studied. Of the 289 isolates obtained from individual
      patients, 173 (59.9%) were serogroup C, 76 (26.3%) were serogroup B, 30 (10.4%)
      were serogroup Y, and 10 (3.5%) were serogroup W135. Ninety-six percent of the
      serogroup C isolates belonged to the ET-15 clone, with an additional 2.3%
      belonging to other electrophoretic types within the ET-37 clonal complex.
      Different antigenic variants of the endemic serogroup C ET-15 clone were
      responsible for localized outbreaks in different parts of the country. One novel
      variant with the antigenic composition of C:2a:P1.1,7 was reported in two
      provinces, Quebec and Ontario. Eighteen percent of the meningococci isolated from
      patients in Ontario belonged to serogroup Y, compared with only 8% in the rest of
      Canada. The current data highlight the importance of strain characterization by
      serogroup, serotype, and serosubtype antigens in providing useful information for
      the surveillance of meningococcal disease in Canada.

PMID- 14663498
TI  - Induction, purification, and characterization of two extracellular alpha-L
      arabinofuranosidases from Fusarium oxysporum.
AB  - In the presence of L-arabinose as sole carbon source, Fusarium oxysporum produces
      two alpha-L-arabinofuranosidases (ABFs) named ABF1 and ABF2, with molecular
      masses of 200 and 180 kDa, respectively. The two F. oxysporum proteins have been
      purified to homogeneity. The purified enzymes are composed of three equal
      subunits and are neutral proteins with pIs of 6.0 and 7.3 for ABF1 and ABF2,
      respectively. With p-nitrophenyl alpha-L-arabinofuranoside (pNPA) as the
      substrate, ABF1 and ABF2 exhibited Km values of 0.39 and 0.28 mmol.L(-1),
      respectively, and Vmax values of 1.6 and 4.6 micromol.min(-1).(mg of protein)(
      1), respectively, and displayed optimal activity at pH 6.0 and 50-60 degrees C.
      ABFs released arabinose only from sugar beet arabinan and not from wheat soluble
      and insoluble arabinoxylans. The enzymes were not active on substrates containing
      ferulic acid ester linked to C-5 and C-2 linkages of pNPA showing that phenolic
      substituents of pNPA sterically hindered the action of ABFs.

PMID- 14663499
TI  - Phenotypic characteristics and population genetics of Enterococcus faecalis
      cultured from patients in Tehran during 2000-2001.
AB  - Conventional bacteriology techniques were used to identify enterococci isolates
      cultured from patients at different hospitals in Tehran during 2000-2001. The
      identification was confirmed using species-specific PCR targeting the D-alanyl-D
      alanine ligase gene. A total of 59 isolates of Enterococcus faecalis were
      identified. The rates of resistance to different antibiotics were in the
      following order: penicillin 84%, ciprofloxacin 42%, high-level gentamicin 30%,
      nitrofurantoin 14%, imipenem 4%, and chloramphenicol 2%. Resistance to ampicillin
      was found to be rare among the Iranian isolates of E. faecalis. Multi-locus
      enzyme electrophoresis was then used to analyze the strains. Forty-five
      electrophoretic types were obtained when 10 enzyme loci were screened. Although
      the collection of bacterial isolates was limited in time and location,
      considerable heterogeneity was found. Analysis of strains for linkage
      disequilibrium demonstrated that the studied population is not clonal, since the
      index of association was not significantly different from zero (Ia = 0.0296).
      Enterococcus faecalis isolates recovered from patients in Tehran were genetically
      diverse and seemed to possess a high potential for genetic recombinations, though
      none were resistant to vancomycin.

PMID- 14663500
TI  - Attempts to inhibit ruminal methanogenesis by blocking pyruvate oxidative
      decarboxylation.
AB  - The inhibition of pyruvate oxidative decarboxylation as a means of decreasing
      ruminal methanogenesis in vitro was studied. In the first experiment, the
      addition of adenosine and adenine (with and without ribose) to ruminal batch
      cultures did not decrease methanogenesis. In the second experiment, the addition
      of oxythiamin decreased methanogenesis by 23%. In the third experiment, three
      pyruvate derivatives did not inhibit methanogenesis, although hydroxypyruvate
      improved organic matter fermentation from 57.8% to 64.2%. The additives did not
      seem to inhibit pyruvate oxidative decarboxylation.

PMID- 14663501
TI  - The role of connective tissue growth factor, a multifunctional matricellular
      protein, in fibroblast biology.
AB  - Connective tissue growth factor (CTGF, CCN2), a member of the CCN family of
      proteins, is a cysteine-rich proadhesive matricellular protein that plays an
      essential role in the formation of blood vessels, bone, and connective tissue. As
      expression of this protein is potently induced by transforming growth factor-beta
      (TGFbeta), it has been hypothesized that CTGF mediates several of the downstream
      actions of TGFbeta. In particular, CTGF is profibrotic, as CTGF is overexpressed
      in fibrotic disease and synergizes with TGFbeta to promote sustained fibrosis in
      vivo. Over the last several years, key data regarding the developmental role and
      structure and function relationship of CTGF have emerged. In addition, increased
      information concerning the mechanisms underlying the control of CTGF expression
      in normal and fibrotic cells and the signal transduction pathways through which
      CTGF acts on cells has been uncovered. This review summarizes the current state
      of knowledge regarding CTGF biology.

PMID- 14663502
TI  - Different methods of membrane domains isolation result in similar 2-D
      distribution patterns of membrane domain proteins.
AB  - Membrane domains are highly specialized parts of the cell plasma membrane,
      carrying on and augmenting the incoming signals. To study their structural and
      functional properties, it is crucial to find the least damaging mode of their
      isolation. Using two different cell lines, epithelial HEK cells (clone E2M11) and
      S49 lymphoma cells, three methods of membrane domain isolation (i.e., detergent
      extraction, alkaline treatment, and "drastic" homogenization) were tested for
      similarity and reproducibility by 2-D electrophoresis. Our data show that the
      protein composition of membrane domains obtained by different isolation methods
      is similar and that approximately 60% of the spots are present in all membrane
      domain preparations. Furthermore, the same degree of similarity of 2-D profiles
      of the most intensively silver stained spots found in membrane domains of the two
      cell lines derived from different tissues suggests that the composition of a
      large part of membrane domains proteins is conservative. We suggest that these
      proteins may either be involved in the organization of membrane domain structure
      or represent the conservative component of signal transduction machinery.

PMID- 14663503
TI  - A novel ribonuclease from the veiled lady mushroom Dictyophora indusiata.
AB  - A ribonuclease (RNase), exhibiting a molecular mass of 28 kDa and specificity
      toward polyU and polyA and possessing an N-terminal sequence dissimilar to
      previously reported mushroom RNases, was isolated from dried fruiting bodies of
      veiled lady mushroom (Dictyophora indusiata). It demonstrated an RNase activity
      of 564 U/mg toward yeast transfer RNA. The RNase was adsorbed on DEAE-cellulose,
      CM-Sepharose, and Q-Sepharose. It demonstrated a pH optimum of 4-4.5 and a
      temperature optimum of 60 degrees C. There was a loss of RNase activity at
      temperatures above 60 degrees C.

PMID- 14663504
TI  - Effect of ethanol on cell growth and cholesterol metabolism in cultured Hep G2
      cells.
AB  - The Hep G2 human hepatoma cell line has been recognized as an excellent in vitro
      human model system. For this reason, this line was used to study the effect of
      ethanol on HMG-CoA reductase activity concerning cell growth and cholesterol
      metabolism. Cells were incubated in ethanol-containing medium (0-400 mmol/L) for
      up to 102 h. Ethanol caused an inhibition in the growth rate and in HMG-CoA
      reductase activity that could be reverted by the removal of ethanol from the
      culture medium, indicating no cellular damage. These changes cannot be ascribed
      to the regulatory effect of cholesterol levels, since its content was not
      modified either in the cells or in the medium. The addition of mevalonate to the
      culture medium could not revert the growth rate inhibition evoked by ethanol.
      Moreover, ethanol produced an increment in the cholesterol efflux in
      [3H]cholesterol-prelabeled cells. We conclude that the decrease in HMG-CoA
      reductase activity evoked by ethanol treatment on Hep G2 cells would not be the
      cause but the consequence of the impairment in cellular growth, since this
      impairment could not be reverted by the addition of mevalonate to the culture
      medium.

PMID- 14663505
TI  - Purification of glysojanin, an antifungal protein, from the black soybean Glycine
      soja.
AB  - A monomeric protein, with a molecular mass of 25 kDa and an N-terminal sequence
      resembling a segment of chitin synthase, was isolated from the seeds of the black
      soybean Glycine soja. The protein, designated glysojanin, demonstrated potent
      antifungal activity against the fungi Fusarium oxysporum and Mycosphaerella
      arachidicola. It inhibited HIV-1 reverse transcriptase with an IC50 of 47
      micromol/L, [methyl-3H]thymidine incorporation by mouse spleen cells with an IC50
      of 175 micromol/L, and translation in the rabbit reticulocyte lysate with an IC50
      of 20 micromol/L. Glysojanin was purified using a procedure that involved ion
      exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel
      blue gel, ion-exchange chromatography by fast protein liquid chromatography on
      Mono S, and gel filtration by fast protein liquid chromatography on Superdex 75.

PMID- 14663506
TI  - Shall we dance or shall we fight? Using DNA sequence data to untangle
      controversies surrounding sexual selection.
AB  - Population and evolutionary genetics studies have largely benefitted from
      advances in DNA manipulation and sequencing, as well as DNA data analysis
      techniques. Molecular evolution studies of male reproductive genes show a pattern
      of rapid evolution shaped, in some cases, by an adaptive selective process.
      Despite the large body of data on male reproductive genes, the female side of the
      story has remained unexplored. The few cases of female egg receptors analyzed
      also show rapid evolution. However, to disentangle between competing hypotheses
      on how selection operates on male x female molecular interaction leading to
      fertilization, we need to find male and female molecules that are partners in
      fertilization. A conflict model of sexual selection (similar to a host-parasite
      model) assumes a male-driven system where females are being forced under
      suboptimal conditions. This predicts that the amount of divergence at a female
      receptor depends on the amount of divergence among the male reproductive proteins
      that it binds (i.e., males are leading). Under a classical model of runaway
      sexual selection, female protein receptors might be the key to the rapid
      molecular changes observed in male reproductive proteins and higher divergence
      should be expected among female receptors than among their respective male
      binding proteins.

PMID- 14663507
TI  - DNA and the revolutions of molecular evolution, computational biology, and
      bioinformatics.
AB  - The discovery of the structure of DNA was a necessary prerequisite for
      determining the sequence of DNA molecules. Technological advances have now made
      it possible to sequence DNA rapidly and has resulted in public databases with
      over 30 billion nucleotides of known sequence. The analysis of these data has
      lead to new fields of science and to amazing advances in our understanding of
      evolution.

PMID- 14663508
TI  - The double-stranded DNA helix in recombination at meiosis.
AB  - The nature of meiotic genetic recombination was resolved at the DNA level by the
      1953 Watson and Crick model. What remains to be determined are the roles of the
      various recombination proteins and the distribution and localization of
      recombination events in the meiotic prophase nucleus.

PMID- 14663509
TI  - Darwin to DNA, molecules to morphology: the end of classical population genetics
      and the road ahead.
AB  - Molecular reductionism has permeated all of biology and because of successive new
      technical breakthroughs it has succeeded in unraveling the structural details of
      genes and genomes. The molecular revolution has reached its reductionist limit,
      i.e., the study of component parts in isolation, and is ready to come full circle
      through genomics, proteomics, and gene expression studies back to the phenotype
      and bring evolutionary biology to confront the Darwinian paradigm, the
      relationship between gene, organism, and environment. Classical experimental
      population genetics, dealing with genetic polymorphism and estimation of
      selection coefficients on a gene-by-gene basis, is coming to an end and a new era
      of interdisciplinary and interactive biology focusing on dynamic relationships
      among gene, organism, and environment has begun. In the new population genetics,
      there will be a shift in focus from single genes to gene networks, from gene
      structure to gene-regulation, from additivity to epistasis, and from simple
      phenotypes to gene-interaction networks and the evolution of complex and modular
      systems.

PMID- 14663510
TI  - Visualizing DNA domains and sequences by microscopy: a fifty-year history of
      molecular cytogenetics.
AB  - This short review presents a historical perspective of chromosome research during
      the last 50 years. It shows how molecular knowledge and technology of DNA entered
      cytogenetics step by step making it now daily practice in almost every modern
      chromosome lab. A crucial milestone in these decades has been the development of
      in situ protocols by Pardue and Gall, among others, initially only with isotopic
      labels, and without fluorescence microscopy and sophisticated detection systems.
      But these very first in situ hybridizations played a decisive role in the
      discovery of chromosome banding profiles, which were obtained under specific
      chemical, physical, or enzymatic conditions, thus effecting stainability of
      specific chromosome regions. In the decades thereafter, numerous technical
      improvements were achieved leading to complex multi-colour fluorescence in situ
      hybridization (FISH) protocols for mammals, plants, and insects. Highly improved
      detection systems of the FISH signals further allowed detection of DNA targets of
      up to 50 bp, whereas other protocols, which were developed to stretch chromatin
      fibres to the full length of native DNA, improved spatial resolution of adjacent
      targets in the light microscope to 1 kb.

PMID- 14663511
TI  - Unfolding large-scale maps.
AB  - This is an account of the development and use of genetic maps, from humble
      beginnings at the hands of Thomas Hunt Morgan, to the sophistication of genome
      sequencing. The review charters the emergence of molecular marker maps exploiting
      DNA polymorphism, the renaissance of cytogenetics through the use of fluorescence
      in situ hybridisation, and the discovery and isolation of genes by map-based
      cloning. The historical significance of sequencing of DNA prefaces a section
      describing the sequencing of genomes, the ascendancy of particular model
      organisms, and the utility and limitations of comparative genomic and functional
      genomic approaches to further our understanding of the control of biological
      processes. Emphasis is given throughout the treatise as to how the structure and
      biological behaviour of the DNA molecule underpin the technological development
      and biological applications of maps.

PMID- 14663512
TI  - DNA, chromosomes, and in situ hybridization.
AB  - In situ hybridization is a powerful and unique technique that correlates
      molecular information of a DNA sequence with its physical location along
      chromosomes and genomes. It thus provides valuable information about physical map
      position of sequences and often is the only means to determine abundance and
      distribution of repetitive sequences making up the majority of most genomes.
      Repeated DNA sequences, composed of units of a few to a thousand base pairs in
      size, occur in blocks (tandem or satellite repeats) or are dispersed (including
      transposable elements) throughout the genome. They are often the most variable
      components of a genome, often being species and, occasionally, chromosome
      specific. Their variability arises through amplification, diversification and
      dispersion, as well as homogenization and loss; there is a remarkable correlation
      of molecular sequence features with chromosomal organization including the length
      of repeat units, their higher order structures, chromosomal locations, and
      dispersion mechanisms. Our understanding of the structure, function,
      organization, and evolution of genomes and their evolving repetitive components
      enabled many new cytogenetic applications to both medicine and agriculture,
      particularly in diagnosis and plant breeding.

PMID- 14663513
TI  - Epigenetics and the renaissance of heresy.
AB  - Classic neo-Darwinian theory is predicated on the notion that all heritable
      phenotypic change is mediated by alterations of the DNA sequence in genomes.
      However, evidence is accumulating that stably heritable phenotypes can also have
      an epigenetic basis, lending support to the long-discarded notion of inheritance
      of acquired traits. As many of the examples of epigenetic inheritance are
      mediated by position effects, the possibility exists that chromosome
      rearrangements may be one of the driving forces behind evolutionary change by
      exerting position effect alterations in gene activity, an idea articulated by
      Richard Goldschmidt. The emerging evidence suggests that Goldschmidt's
      controversial hypothesis deserves a serious reevaluation.

PMID- 14663516
TI  - Two kinds of sex ratio distorters in a moth, Ostrinia scapulalis.
AB  - We surveyed female-biased sex ratio traits (SR traits) in a moth, Ostrinia
      scapulalis (Lepidoptera: Crambidae) from six geographic locations in Japan. A
      small proportion (8.3%) of females showed the SR trait. About half of them were
      associated with a Wolbachia infection (SRw+), whereas the remaining ones were not
      (SRw-). No significant differences in frequencies were detected among locations
      and years for either SRw+ or SRw- females. In SRw+ matrilines, the SR trait was
      inherited. Curing the Wolbachia infection by tetracycline at the larval stages
      resulted in all-male broods in the next generation. These characteristics were
      identical to the Wolbachia-induced SR trait observed previously in the related
      species Ostrinia furnacalis. The Wolbachia strain in O. scapulalis was
      indistinguishable from that in O. furnacalis in terms of the wsp and ftsZ gene
      sequences, suggesting either that infection originated from a common ancestor of
      the two hosts or that Wolbachia was transmitted horizontally between the host
      species. In SRw- matrilines, on the other hand, the SR trait was not due to
      bacterial infection but some other maternally inherited element, since antibiotic
      treatment had no effect and bacterial PCR did not give the characteristic
      product. In these matrilines, the SR trait occasionally failed to show,
      suggesting the presence of nuclear factor(s) suppressing the SR trait.

PMID- 14663517
TI  - Sexual mosaics induced by tetracycline treatment in the Wolbachia-infected adzuki
      bean borer, Ostrinia scapulalis.
AB  - Wolbachia-infected Ostrinia scapulalis (Lepidoptera: Crambidae) females generate
      all-female or nearly all-female broods. Curing the infection by tetracycline
      treatment during larval stages results in the generation of all-male broods in
      the next generation. Here we show that sexually mosaic offspring are produced by
      Wolbachia-infected females treated with tetracycline at the adult stage. The
      sexual mosaics had wings that were composed of distinctive female and male
      sectors. Besides wings, the sexually dimorphic mid tibiae displayed an
      intermediate morphology in some of the mosaics. Many of the mosaic individuals
      had an abnormal structure of the external genitalia as well, a combination of the
      male uncus and the female ovipositor. We assume that Wolbachia has a feminizing
      effect on O. scapulalis genetic males and, hence, incomplete curing of the
      Wolbachia infection results in the generation of sexually mosaic individuals.

PMID- 14663518
TI  - Relationships in Ananas and other related genera using chloroplast DNA
      restriction site variation.
AB  - Chloroplast DNA (cpDNA) diversity was examined using PCR-RFLP to study
      phylogenetic relationships in Ananas and related genera. One hundred fifteen
      accessions representing the seven Ananas species and seven other Bromelioideae
      including the neighboring monospecific genus Pseudananas, two Pitcairnioideae,
      and one Tillandsioideae were included in the study. Eight primers designed from
      cpDNA were used for generating fragments. Restriction by 18 endonucleases
      generated 255 variable fragments. Dissimilarities were calculated from the
      resulting matrix using the Sokal and Michener index and the neighbor-joining
      method was used to reconstruct the diversity tree. Phylogenetic reconstruction
      was attempted using Wagner parsimony. Phenetic and cladistic analyses gave
      consistent results. They confirm the basal position of Bromelia in the
      Bromelioideae. Ananas and Pseudananas form a monophyletic group, with three
      strongly supported sub-groups, two of which are geographically consistent. The
      majority of Ananas parguazensis accessions constitute a northern group restricted
      to the Rio Negro and Orinoco basins in Brazil. The tetraploid Pseudananas
      sagenarius joins the diploid Ananas fritzmuelleri to constitute a southern group.
      The third and largest group, which includes all remaining species plus some
      accessions of A. parguazensis and intermediate phenotypes, is the most widespread
      and its distribution overlaps those of the northern and southern groups. Ananas
      ananassoides is dominant in this sub-group and highly variable. Its close
      relationship to all cultivated species supports the hypothesis that this species
      is the wild ancestor of the domesticated pineapple. The data indicate that gene
      flow is common within this group and scarcer with both the first and second
      groups. Comparison of cpDNA data with published genomic DNA data point to the
      hybrid origin of Ananas bracteatus and support the autopolyploidy of Pseudananas.
      The Ananas-Pseudananas group structure and distribution are consistent and we
      propose a scenario based on the refugia hypothesis to explain our data. These
      results and hypotheses bring some interesting points to consider in the current
      discussion on Ananas taxonomy.

PMID- 14663519
TI  - Prion protein gene sequence of Canada's first non-imported case of bovine
      spongiform encephalopathy (BSE).
AB  - In May 2003, Canada became the 22nd country outside of the United Kingdom to
      report a case of bovine spongiform encephalopathy (BSE) in an animal not known to
      be imported from a country with cattle previously affected by this fatal,
      transmissible prion disease. Despite extensive testing of thousands of other
      animals that may have been exposed to contaminated feed at the same time as the
      affected animal, no evidence has been found for other infections. This finding
      leaves room for conjectures that the single confirmed case arose spontaneously,
      perhaps (by analogy with human Creutzfeldt-Jakob disease) as a result of a
      somatic protein misfolding event or a novel germline mutation. Here we present
      DNA sequence data from the affected animal's prion protein coding sequence that
      argue definitively against the latter hypothesis.

PMID- 14663520
TI  - Development and characterization of recombinant chromosome substitution lines
      (RCSLs) using Hordeum vulgare subsp. spontaneum as a source of donor alleles in a
      Hordeum vulgare subsp. vulgare background.
AB  - The ancestor of barley (Hordeum vulgare subsp. spontaneum) may be a source of
      novel alleles for crop improvement. We developed a set of recombinant chromosome
      substitution lines (RCSLs) using an accession of H. vulgare subsp. spontaneum
      (Caesarea 26-24, from Israel) as the donor and Hordeum vulgare subsp. vulgare
      'Harrington' (the North American malting quality standard) as the recurrent
      parent via two backcrosses to the recurrent parent, followed by six generations
      of selfing. Here we report (i) the genomic architecture of the RCSLs, as inferred
      by simple sequence repeat (SSR) markers, and (ii) the effects of H. vulgare
      subsp. spontaneum genome segment introgressions in terms of three classes of
      phenotypes: inflorescence yield components, malting quality traits, and
      domestication traits. Significant differences among the RCSLs were detected for
      all phenotypes measured. The phenotypic effects of the introgressions were
      assessed using association analysis, and these were referenced to quantitative
      trait loci (QTL) reported in the literature. Hordeum vulgare subsp. spontaneum,
      despite its overall inferior phenotype, contributed some favorable alleles for
      agronomic and malting quality traits. In most cases, the introgression of the
      ancestral genome resulted in a loss of desirable phenotypes in the cultivated
      parent. Although disappointing from a plant breeding perspective, this finding
      may prove to be a useful tool for gene discovery.

PMID- 14663521
TI  - Simple sequence repeat (SSR) markers linked to E1, E3, E4, and E7 maturity genes
      in soybean.
AB  - Soybean near isogenic lines (NILs), contrasting for maturity and photoperiod
      sensitivity loci, were genotyped with approximately 430 mapped simple sequence
      repeats (SSRs), also known as microsatellite markers. By analysis of allele
      distributions across the NILs, it was possible to confirm the map location of the
      Dt1 indeterminate growth locus, to refine the SSR mapping of the T tawny
      pubescence locus, to map E1 and E3 maturity loci with molecular markers, and to
      map the E4 and E7 maturity loci for the first time. Molecular markers flanking
      these loci are now available for marker-assisted breeding for these traits.
      Analysis of map locations identified a putative homologous relationship among
      four chromosomal regions; one in the middle of linkage group (LG) C2 carrying E1
      and E7, one on LG I carrying E4, one at the top of LG C2, at which there is a
      reproductive period quantitative trait locus (QTL), and the fourth on LG B1.
      Other evidence suggests that homology also exists between the E1 + E7 region on
      LG C2 and a region on LG L linked to a pod maturity QTL. Homology relationships
      predict possible locations in the soybean genome of additional maturity loci, as
      well as which maturity loci may share a common evolutionary origin and similar
      mechanism(s) of action.

PMID- 14663522
TI  - Molecular genetic diversity of the French-American grapevine hybrids cultivated
      in North America.
AB  - French-American hybrid grapevines are most popular in eastern and mid-western
      North America: they are hardy cultivars derived from crosses between the European
      Vitis vinifera and American wild vines. The aim of this study was to characterize
      their genetic background using 6 microsatellite (SSR) markers and a set of 33
      diagnostic RAPD markers. The latter were reproducible with different PCR thermal
      cyclers. Two SSR loci were found to be synonymous, VrZAG47 and VVMD27. The DNA
      profile frequencies estimated for each cultivar were much lower with multi-locus
      SSR data than that obtained from multi-fragment RAPD data. There was no
      significant correlation between the multi-locus DNA profile frequencies derived
      from SSRs and those from RAPDs. Estimates of genetic diversity derived from SSRs
      were generally higher and the average similarity between cultivars was generally
      lower than values reported for subgroups of V. vinifera, in accordance with
      expectations for hybrid cultivars. The phenetic relationships depicted by UPGMA
      (unweighted pair-group method with arithmetic averaging) and neighbor-joining
      analyses of microsatellite data were congruent and, to a large extent, in
      agreement with the known pedigree or history of each cultivar. A major dichotomy
      was observed between one group where the known genetic background was dominated
      by the North American Vitis riparia and Vitis labrusca, and another one where the
      genetic background was dominated by the European V. vinifera. Two Kulhmann
      varieties thought to be synonymous were found to be different, though closely
      related.

PMID- 14663523
TI  - Functional genomic analysis of the 61D-61F region of the third chromosome of
      Drosophila melanogaster.
AB  - Assigning functional significance to completed genome sequences is one of the
      next challenges in biological science. Conventional genetic tools such as
      deficiency chromosomes help assign essential complementation groups to their
      corresponding genes. We describe an F2 genetic screen to identify lethal
      mutations within cytogenetic region 61D-61F of the third chromosome of Drosophila
      melanogaster. One hundred sixteen mutations were identified by their failure to
      complement both Df(3L)bab-PG and Df(3L)3C7. These alleles were assigned to 14
      complementation groups and 9 deficiency intervals. Complementation groups were
      ordered using existing deficiencies, as well as new deficiencies generated in
      this study. With the aid of the genomic sequence, genetic and physical maps in
      the region were correlated by use of PCR to localize the breakpoints of
      deficiencies within a 268-kb genomic contig (GenBank accession No. AC005847). Six
      essential complementation groups were assigned to specific genes, including genes
      encoding a porphobilinogen deaminase and a Sac1-like protein.

PMID- 14663524
TI  - SNP-based codominant markers for a recessive gene conferring resistance to corky
      root rot (Rhizomonas suberifaciens) in lettuce (Lactuca sativa).
AB  - The analysis of F2 progeny and derived F3 families of Lactuca sativa segregating
      for resistance to corky root rot caused by Rhizomonas suberifaciens permitted the
      identification of restriction fragment length polymorphism (RFLP) and single
      nucleotide polymorphism (SNP) markers linked to the recessive resistance gene
      cor. PCR-based markers were identified by bulked segregant analysis (BSA). Allele
      specific primers were generally designed with the 3 terminal base coinciding with
      an SNP, matching one of the alleles and mismatching the other, and with an
      additional subterminal 3 base mismatching both alleles. Codominant, robust, and
      inexpensive molecular markers were obtained that used standardized PCR
      conditions. Some of the markers could be analyzed in multiple Lactuca mapping
      populations that did not segregate for disease resistance allowing the cor locus
      to be located on several maps. The consistent low density of markers around cor
      in these maps suggests that cor may be in an area with an elevated rate of
      recombination. Evaluation of these markers in a large sample of cultivars and
      landraces identified pairs of flanking polymorphic markers that can be used for
      marker-assisted selection of corky root resistance.

PMID- 14663525
TI  - Karyotype analysis in Hyacinthella dalmatica (Hyacinthaceae) reveals vertebrate
      type telomere repeats at the chromosome ends.
AB  - Chromosome analysis of three different populations of Hyacinthella dalmatica
      (Lallem.) Trinajstic, an endemic species of the coastal region of southeastern
      Europe, showed a unique chromosome number, 2n = 2x = 20, and bimodal karyotype
      with one large and nine smaller pairs of chromosomes. Staining with fluorochromes
      CMA3 (chromomycin A3) and DAPI (4,6-diamidino-2-phenylindole) revealed
      heterochromatic regions associated with NORs, centromeres, and several
      interstitial heterochromatic bands on the longest chromosome pair. Double-target
      FISH with two ribosomal DNA probes revealed one locus of 5S rRNA genes in the
      pericentromeric region of chromosome pair 3 and one locus of 18S-5.8S-26S rRNA
      genes on the short arm of chromosome pair 4 in all plants and populations
      analyzed. Southern hybridization analysis and FISH experiments demonstrated that
      the distal ends of H. dalmatica chromosomes contain the vertebrate telomere (5'
      TTAGGG-3') repeat type rather than the Arabidopsis (5'-TTTAGGG-3') heptamer, and
      so suggest that this Asparagales species along with Aloe and Othocallis contains
      the vertebrate-type telomere repeat.

PMID- 14663526
TI  - DNA polymorphism in the stem nematode Ditylenchus dipsaci: development of
      diagnostic markers for normal and giant races.
AB  - DNA polymorphism in the Ditylenchus dipsaci complex was investigated using
      amplified fragment length polymorphism (AFLP) to determine the relationships
      among populations growing mainly on Vicia faba and to develop diagnostic markers.
      Twenty-two populations of D. dipsaci originating from different geographical
      areas and one population of Ditylenchus myceliophagus were used. AFLP proved to
      be a powerful method to reveal intraspecific polymorphism even within the giant
      type. The analysis showed a clear distinction between the giant and normal
      populations, with genetic distances similar to those observed between normal
      populations and D. myceliophagus or giant populations and D. myceliophagus,
      strengthening the hypothesis that these two nematode types could be considered
      distinct species. Two specific AFLP markers differentiating the two types were
      converted into sequenced characterized amplified region (SCAR) markers. Used in a
      multiplex PCR, the SCAR primers proved to be a rapid and efficient tool to
      identify the giant and the normal types of D. dipsaci.

PMID- 14663527
TI  - Structural organization of the barley D-hordein locus in comparison with its
      orthologous regions of wheat genomes.
AB  - D hordein, a prolamin storage protein of barley endosperms, is highly homologous
      to the high molecular weight (HWM) glutenin subunits, which are the major
      determinants of bread-making quality in wheat flour. In hexaploid wheat (AABBDD),
      each genome contains two paralogous copies of HMW-glutenin genes that encode the
      x- and y-type HMW-glutenin subunits. Previously, we reported the sequence
      analysis of a 102-kb genomic region that contains the HMW-glutenin locus of the D
      genome from Aegilops tauschii, the donor of the D genome of hexaploid wheat.
      Here, we present the sequence analysis of a 120-kb D-hordein region of the barley
      genome, a more distantly related member of the Triticeae grass tribe. Comparative
      sequence analysis revealed that gene content and order are generally conserved.
      Genes included in both of these orthologous regions are arranged in the following
      order: a Xa21-like receptor kinase, an endosperm globulin, an HMW prolamin, and a
      serine (threonine) protein kinase. However, in the wheat D genome, a region
      containing both the globulin and HMW-glutenin gene was duplicated, indicating
      that this duplication event occurred after the separation of the wheat and barley
      genomes. The intergenic regions are divergent with regard to the sequence and
      structural organization. It was found that different types of retroelements are
      responsible for the intergenic structure divergence in the wheat and barley
      genomes. In the barley region, we identified 16 long terminal repeat (LTR)
      retrotransposons in three distinct nested clusters. These retroelements account
      for 63% of the contig sequence. In addition, barley D hordein was compared with
      wheat HMW glutenins in terms of cysteine residue conservation and repeat domain
      organization.

PMID- 14663528
TI  - Transmission of alien chromosomes from selfed progenies of a complete set of
      Allium monosomic additions: the development of a reliable method for the
      maintenance of a monosomic addition set.
AB  - Selfed progeny of a complete set of Allium fistulosum - Allium cepa monosomic
      addition lines (2n = 2x + 1 = 17, FF+1A-FF+8A) were produced to examine the
      transmission rates of respective alien chromosomes. All eight types of the selfed
      monosomic additions set germinable seeds. The numbers of chromosomes (2n) in the
      seedlings were 16, 17, or 18. The eight extra chromosomes varied in transmission
      rate (%) from 9 (FF+2A) to 49 (FF+8A). The complete set of monosomic additions
      was reproduced successfully by self-pollination. A reliable way to maintain a set
      of Allium monosomic additions was developed using a combination of two crossing
      methods, selfing and female transmission. FF+8A produced two seedlings with 18
      chromosomes. Cytogenetical analyses, including GISH, showed that the seedlings
      were disomic addition plants carrying two entire homologous chromosomes from A.
      cepa in an integral diploid background of A. fistulosum. Flow cytometry analysis
      showed that a double dose of the alien 8A chromosome caused fluorescence
      intensity values spurring in DNA content, and isozyme analysis showed increased
      glutamate dehydrogenase activity at the gene locus Gdh-1.

PMID- 14663529
TI  - Different patterns of gene silencing in position-effect variegation.
AB  - Position-effect variegation (PEV) results when a fully functional gene is moved
      from its normal position to a position near to a broken heterochromatic
      euchromatic boundary. In this new position, the gene, while remaining unaltered
      at the DNA level, is transcriptionally silenced in some cells but active in
      others, producing a diagnostic mosaic phenotype. Many variegating stocks show
      phenotypic instability, in that the level of variegation is dramatically
      different in different isolates or when out crossed. To test if this phenotypic
      instability was due to segregation of spontaneously accumulated mutations that
      suppress variegation, four different and well-characterized strains showing PEV
      for the white+ gene (wm4, wmMc, wm51b, and wmJ) and representing both large and
      small spot variegators were repeatedly out crossed to a strain free of modifiers,
      and the phenotypes of these variegators were monitored for 30 generations. Once
      free of modifiers, these variegating strains were then allowed to reaccumulate
      modifiers. The spontaneous suppressors of variegation were found to include both
      dominant and recessive, autosomal and X-linked alleles selected to reduce the
      detrimental effects of silencing white+ and adjacent genes. The time of peak
      sensitivity to temperature during development was also determined for these four
      variegators. Although large and small spot variegators have previously been
      attributed to early and late silencing events, respectively, the variegators we
      examined all shared a common early period of peak sensitivity to temperature.
      Once free of their variegation suppressors, the different variegating strains
      showed considerable differences in the frequency of inactivation at a cellular
      level (the number of cells showing silencing of a given gene) and the extent of
      variegation within the cell (the number of silenced genes). These results suggest
      that large and small spot variegation may be a superficial consequence of
      spontaneous variegation suppressors. The nature and number of these spontaneous
      variegation suppressors depends on the number of genes silenced in a given
      variegating rearrangement. These results are interpreted in the context of a
      model that proposes that the different underlying patterns of gene silencing seen
      in PEV can be attributed directly to the formation of heterochromatin domains
      possessing different properties of propagation during cell division.

PMID- 14663530
TI  - Distribution of highly repeated DNA sequences in species of the genus Lens
      Miller.
AB  - Multiple-target fluorescence in situ hybridization (FISH) was applied on mitotic
      chromosomes of seven Lens taxa using two highly repetitive sequences (pLc30 and
      pLc7) isolated from the cultivated lentil and the multigene families for the 18S
      5.8S-25S (pTa71) and 5S rRNA (pTa794) from wheat simultaneously as probes. The
      number and location of pLc30 and pLc7 sites on chromosomes varied markedly among
      the species, whereas the hybridization pattern of 5S rDNA and 18S-5.8S-25S rDNA
      was less variable. In general, each species showed a typical FISH karyotype and
      few differences were observed among accessions belonging to the same species,
      except for the accessions of Lens odemensis. The most similar FISH karyotype to
      the cultivated lentil is that of Lens culinaris subsp. orientalis, whereas Lens
      nigricans and Lens tomentosus are the two species that showed the most divergent
      FISH patterns compared with all taxa for number and location of pLc30 and 18S
      5.8S-25S rDNA sites.

PMID- 14663531
TI  - Medical students mirror and hold mirrors.

PMID- 14663532
TI  - The newest team member?

PMID- 14663534
TI  - Birth can be a hazardous journey: electronic fetal monitoring does not help.
AB  - Intrapartum fetal health surveillance, in particular electronic fetal heart-rate
      monitoring (EFM), is a perinatal issue that has sparked much debate both
      nationally and internationally. Prevention of cerebral palsy is a major objective
      of all health-care providers when assessing fetal health in labour. The Fetal
      Health Surveillance Working Group of the Society of Obstetricians and
      Gynaecologists of Canada (SOGC) should be commended for its efforts in presenting
      and discussing the literature and for raising important issues in EFM in the
      SOGC's Clinical Practice Guideline on Standard Fetal Surveillance in Labour,
      published in JOGC in March 2002, the first half of the SOGC document Fetal Health
      Surveillance in Labour. These, as all, SOGC Clinical Practice Guidelines are
      widely used by hospitals and health-care providers when evaluating practices in
      their own environments, and we believe, as practitioners of and investigators in
      fetal health surveillance, that there is not good supporting evidence for
      recommending continuous intrapartum EFM for pregnancies in which there is an
      increased risk of perinatal death, cerebral palsy, or neonatal encephalopathy, or
      when oxytocin is being used for induction of labour, and that if we recommend
      that the fetal heart be electronically monitored while the nurse is elsewhere, we
      are on a slippery slope. We encourage reopening discussion regarding these
      recommendations in the document.

PMID- 14663535
TI  - Cyproterone acetate with ethinylestradiol as a risk factor for venous
      thromboembolism: an epidemiological evaluation.
AB  - OBJECTIVE: To review the incidence of venous thromboembolism (VTE) in association
      with combined cyproterone acetate and ethinylestradiol (CPA/EE) use, compared to
      the incidence of VTE in association with conventional oral contraceptive (OC)
      use, in women aged 14 to 49 years. METHODS: A review consistent with the
      guidelines of "best evidence synthesis" was conducted on 6 peer-reviewed,
      controlled epidemiological studies reporting both outcome numerators and exposure
      denominators. Relative risks as the estimate of the association between CPA/EE
      and the clinical outcome of VTE were set aside in favour of absolute incidence
      rates, rate differences, or attributable risks. RESULTS: The range of absolute
      incidence rates of VTE among CPA/EE users varied from 1.2 to 9.9 per 10 000 women
      years (WYs). All other marketed conventional OCs were the reference. In 6 studies
      conducted in 3 European countries, CPA/EE exhibited an attributable risk in women
      not higher than 0.04% when compared to approved conventional OCs. Except for 1
      study exhibiting a small statistically significant benefit, there was no
      difference between the incidence rates of VTE among CPA/EE users and those among
      conventional OC users. VTE as an adverse event for CPA/EE was either rare or very
      rare, according to the criteria set by the World Health Organization/ Council for
      International Organizations of Medical Sciences. No deaths were reported in the
      studies reviewed. CONCLUSIONS: The evidence in the worldwide literature does not
      demonstrate an excess of health-threatening harm for CPA/EE. A best-evidence
      synthesis, using sound epidemiological methods, showed clearly that the risks of
      VTE among CPA/EE users do not exceed the risks of VTE among conventional OC
      users.

PMID- 14663536
TI  - Influenza-like illness during pregnancy: results from a study in the eastern
      townships, Province of Quebec.
AB  - OBJECTIVES: (1) To assess the frequency of influenza and influenza-like illness
      (ILI) during pregnancy; (2) to explore the associated risk of adverse maternal
      and fetal outcomes. METHODS: All women who delivered at the Sherbrooke University
      Hospital in the province of Quebec during the period of February 15 to April 30,
      2002, were invited to complete a questionnaire. Medical records of participating
      women and of their infants were reviewed. Complement-fixing antibody titres
      against influenza A were measured in paired sera drawn during antenatal screening
      and at delivery. RESULTS: The study participation rate was 96.3%. Nine of 517
      women stated that they had received the influenza vaccine during pregnancy, and
      only 3 of 47 women with a chronic pulmonary disease had been immunized. Overall,
      464 ILI episodes were reported by 331 women, and a significant maternal
      complication occurred in 8 cases. ILI episodes resulted in medical consultations
      in 55.4% of cases, and in antibiotic prescriptions in 13.8% of cases. There was
      no indication of an increased frequency of adverse perinatal outcomes associated
      with ILI during pregnancy. Paired sera were available for 156 participants and
      seroconversion was observed in 6.6%. CONCLUSIONS: ILI during pregnancy was
      associated with health services utilization but complications were infrequent.
      More studies are needed to demonstrate the usefulness of routine vaccination of
      healthy pregnant women against influenza.

PMID- 14663537
TI  - Cryopreserved human embryos in Canada and their availability for research.
AB  - OBJECTIVE: To determine the number of cryopreserved human embryos at all Canadian
      in vitro fertilization (IVF) clinics, the number of these embryos that have been
      donated to research, and the consent processes regarding the disposition of
      embryos no longer required for reproductive purposes. METHODS: A questionnaire
      was mailed to 24 fertility clinics identified as conducting IVF and
      cryopreservation, inviting completion of the questionnaire by telephone. Thirteen
      clinics (response rate 54%) completed the survey. RESULTS: As of August 2003, all
      13 clinics cryopreserve embryos not required for intrauterine transfer; in total,
      15,615 embryos are currently in storage in these clinics. Nine clinics
      specifically offer patients the option of donating embryos to research; in total,
      299 embryos have been allocated for research, about 2% of all embryos stored by
      these 13 clinics. All 9 clinics routinely seek consent for research use of
      embryos, with 7 clinics currently using such embryos for research to improve
      clinic practices. CONCLUSION: The results highlight the difficulties of gathering
      accurate data on assisted human reproduction and related research in a context
      where there is no legislation governing these practices. Nonetheless, the data
      suggest there are very few cryopreserved embryos in Canada available for research
      and that even fewer of these may be potentially eligible for research due to
      incomplete or inadequate consent processes.

PMID- 14663538
TI  - Utilizing best practice methods to improve labour management in a partnership of
      five hospitals.
AB  - OBJECTIVE: To assess the use of "Best Practice" methods as a means of improving
      obstetrical care pertaining to labour management and Caesarean birth in a
      partnership group of 5 hospitals, 4 with birthing rates of 50 to 175 women a
      year, and the fifth with a birthing rate of approximately 1000 women a year.
      METHODS: The Labour Management module of the Advances in Labour and Risk
      Management (ALARM) Best Practice course of the Society of Obstetricians and
      Gynaecologists of Canada (SOGC) was tested on the 4 Level I rural hospitals and 1
      modified Level II hospital in a small city in the Huron Perth Hospitals. The
      outcomes assessed were the module's effectiveness as a Continuing Medical
      Education (CME) tool; its effectiveness at promoting common practice guidelines;
      and its effectiveness at improving communication and co-operation. RESULTS: From
      the 5 participating partnership hospitals, 3 obstetricians, 28 family physicians,
      and 5 midwives were eligible to participate. Of these 36 clinicians, 80%
      completed the Pre-study Phase, which included auditing their practice for Labour
      Management; 94% attended the workshops; and 67% completed the Post-study Audit.
      Common practice changes were identified through the workshops and post-study
      results showed success in their implementation. A Post-study Questionnaire
      indicated improved co-operation and communication in the partnership hospitals.
      CONCLUSIONS: The Management of Labour module of the SOGC ALARM Best Practice
      course was successful in improving obstetrical practice in the partnership group
      of hospitals tested. This method promoted the use of common practice guidelines
      at the bedside and also improved communication and co-operation in the hospital
      partnership.

PMID- 14663539
TI  - SOGC Policy Statement: Sexual health counselling by physicians.

PMID- 14663540
TI  - SOGC Policy Statement: Diversity.

PMID- 14663541
TI  - SOGC Policy Statement: Conflict of interest.

PMID- 14663542
TI  - Proton MR spectroscopy in neuroborreliosis: a preliminary study.
AB  - We report results of a magnetic resonance spectroscopy (MRS) study in 12 patients
      with neuroborreliosis. We used a PRESS sequence, placing an 8 cm3 voxel in normal
      appearing white matter of the frontal lobe. Peaks indicating N-acetylaspartate
      (NAA), choline (Cho), creatine (Cr), myo-inositol (mI), lipids (Lip) and lactate
      (Lac) were identified and ratios of NAA/Cr, Cho/Cr, mI/Cr, Lip/Cr, Lac/Cr
      calculated. Significant increases in Cho/Cr and Lip/Cr were noted. No abnormality
      was found in mean NAA/Cr and Lac/Cr, but in four patients there was a decreased
      NAA peak; mI/Cr ratio was slightly increased. Although the spectroscopic profile
      in patients with neuroborreliosis seems to be nonspecific, MRS might be useful
      for assessing tissue damage of the central nervous system.

PMID- 14663543
TI  - Influence of whole-body pitch tilt and kinesthetic cues on the perceived gravity
      referenced eye level.
AB  - We investigated the effects of whole body tilt and lifting the arm against
      gravity on perceptual estimates of the Gravity-Referenced Eye Level (GREL), which
      corresponds to the subjective earth-referenced horizon. The results showed that
      the perceived GREL was influenced by body tilt, that is, lowered with forward
      tilt and elevated with backward tilt of the body. GREL estimates obtained by arm
      movements without vision were more biased by whole-body tilt than purely visual
      estimates. Strikingly, visual GREL estimates became more dependent on whole-body
      tilt when the indication of level was obtained by arm lifting. These findings
      indicate that active motor involvement and/or the addition of kinesthetic
      information increases the body tilt-induced bias when making GREL judgements. The
      introduction of motor/kinaesthetic cues may induce a switch from a semi
      geocentric to a more egocentric frame of reference. This result challenges the
      assumption that combining non-conflicting multiple sensory inputs and/or using
      intermodal information provided during action should improve perceptual
      performance.

PMID- 14663544
TI  - A study of the chemiluminescence behavior of myoglobin with luminol and its
      analytical applications.
AB  - A chemiluminescence signal at 425 nm was observed when ferric state myoglobin was
      mixed with luminol in alkaline medium. Because the signal was remarkably enhanced
      in the presence of Fe(CN)6(4-), analytical applications were investigated in a
      flow-injection system. The increase in chemiluminescence was linearly dependent
      on myoglobin concentration in the range 0.1 to 100 nmol L(-1), and the limit of
      detection was 0.04 nmol L(-1) with relative standard deviation 3.2% (3 sigma). It
      was also found that binding of Mb with the ligands CN-, SCN-, and F-
      significantly inhibited the chemiluminescence reaction. The linear dynamic ranges
      for the ligands were 1.0-300.0, 0.1-3.0, and 0.5-100.0 nmol L(-1), and the limits
      of detection (S/N=3) 0.4, 0.04, and 0.2 nmol L(-1), for F-, CN-, and SCN-,
      respectively. The relative standard deviations were 5.32%, 6.13%, and 3.38% for
      0.1 nmol L(-1) CN-, 0.5 nmol L(-1) SCN-, and 1.0 nmol L(-1) F-, respectively. At
      a flow rate of 2.0 mL min(-1) the assay could be accomplished in 1 min, including
      sampling and washing. The method has been successfully applied to the
      determination of myoglobin in human urine and F- in water samples. A possible
      mechanism of chemiluminescence production by myoglobin and luminol is presented.

PMID- 14663545
TI  - Chromotropic acid, a fluorogenic chelating agent for aluminium(III).
AB  - Complexation of aluminium(III) with the fluorogenic ligand chromotropic acid (4,5
      dihydroxynaphthalene-2,7-disulfonic acid) has been revisited with the aim of
      using enhancement of the fluorescence intensity as an analytical tool.
      Complexation at the optimum pH approximately 4 was shown to lead to a 1:1 complex
      with a stability constant log beta110=18.4 +/- 0.7. The fluorogenic effect was
      thoroughly investigated. Nearly selective excitation of the chelate rather than
      the ligand could be achieved at wavelengths longer than 360 nm. For analytical
      purposes the main interfering ion was Ga3+. The strongest competing ligand was
      shown to be citric acid. Competitive complexation by acetate or formate ions can
      also make their use in a buffer at the usual concentration, 0.2 mol L(-1),
      questionable, whereas a 10(-2) mol L(-1) formic acid buffer was shown to be a
      good alternative. The calibration plot showed that the dependence of response on
      Al(III) concentration was linear up to 500 microg L(-1); the detection limit was
      0.65 microg L(-1) (3 SDblank, n=10, SD= +/- 1.4% at 10 microg L(-1) and +/- 0.8%
      at 100 microg L(-1)). The analytical procedure was successfully applied to
      several samples of tap water and the results were in good agreement with those
      from AAS determination.

PMID- 14663546
TI  - Application of chemometric methods to the investigation of main microcontaminant
      sources of endocrine disruptors in coastal and harbour waters and sediments.
AB  - Identification, resolution and distribution of main microcontaminant sources of
      endocrine disruptors in Spanish harbours, coastal waters and sediments are
      investigated using chemometric methods. We investigated eighteen different
      endocrine disruptor chemical compounds, including non-ionic surfactants, their
      degradation products and linear alkylbenzene sulfonates, found in a total number
      of 74 samples (35 water samples and 39 sediment samples) over a period of 16
      months from March 1999 to July 2000, and in 32 different geographical sites along
      the Spanish Mediterranean Coast (e.g. Barcelona, Tarragona, Almeria Harbour,
      Malaga and the Bay of Cadiz). Main environmental contamination sources of these
      endocrine disruptor compounds were investigated and interpreted according to
      their chemical composition and according to their resolved geographical
      distribution profiles.

PMID- 14663547
TI  - Interpreting conformational effects in protein nano-ESI-MS spectra.
AB  - Nano-electrospray-ionization mass spectrometry (nano-ESI-MS) is employed here to
      describe equilibrium protein conformational transitions and to analyze the
      influence of instrumental settings, pH, and solvent surface tension on the charge
      state distributions (CSD). A first set of experiments shows that high flow rates
      of N(2) as curtain gas can induce unfolding of cytochrome c (cyt c) and myoglobin
      (Mb), under conditions in which the stability of the native protein structure has
      already been reduced by acidification. However, it is possible to identify
      conditions under which the instrumental settings are not limiting factors for the
      conformational stability of the protein inside ESI droplets. Under such
      conditions, equilibrium unfolding transitions described by ESI-MS are comparable
      with those obtained by other established biophysical methods. Experiments with
      the very stable proteins ubiquitin (Ubq) and lysozyme (Lyz) enable testing of the
      influence of extreme pH changes on the ESI process, uncoupled from acid-induced
      unfolding. When HCl is used for acidification, Ubq and Lyz mass spectra do not
      change between pH~7 and pH 2.2, indicating that the CSD is highly characteristic
      of a given protein conformation and not directly affected by even large pH
      changes. Use of formic or acetic acid for acidification of Ubq solutions results
      in major spectral changes that can be interpreted in terms of protein unfolding
      as a result of the increased hydrophobicity of the solvent. On the other hand,
      Lyz, cyt c, and Mb enable direct comparison of protein CSD (corresponding to
      either the folded or the unfolded protein) in HCl or acetic acid solutions at low
      pH. The values of surface tension for these solutions differ significantly.
      Confirming indications already present in the literature, we observe very similar
      CSD under these solvent conditions for several proteins in either compact or
      disordered conformations. The same is true for comparison between water and water
      acetic acid for folded cyt c and Lyz. Thus, protein CSD from water-acetic
      solutions do not seem to be limited by the low surface tension of acetic acid as
      previously suggested. This result could reflect a general lack of dependence of
      protein CSD on the surface tension of the solvent. However, it is also possible
      that the effect of acetic acid on the precursor ESI droplets is smaller than
      generally assumed.

PMID- 14663548
TI  - Endocrine disruptors.

PMID- 14663549
TI  - Hyperthermic and neurotoxic effect of 3,4-methylenedioxymethamphetamine (MDMA) in
      guinea pigs.

PMID- 14663551
TI  - Fine-tuning risperidone dosage for acutely exacerbated schizophrenia: clinical
      determinants.
AB  - RATIONALE: Risperidone doses for acute schizophrenia were rather high in most
      recent studies. OBJECTIVES: We tested a hypothesis that fine-tuning risperidone
      dosage to relieve side effects still yields efficacy. Clinical factors
      influencing the dosing were also determined. METHODS: One hundred and forty-six
      schizophrenia inpatients with acute exacerbation entered a prospective, 6-week,
      repeated measures study. Risperidone doses were titrated to 6 mg/day (if
      tolerable) within 7 days, but were lowered thereafter if adverse reactions
      appeared. Efficacy and safety were measured biweekly. RESULTS: Forty-eight
      patients tolerated the 6-mg/day target dose well, while the other 98 received
      lower final doses (mean+/-SD=3.4+/-0.9 mg/day) to curtail adverse effects. At
      endpoint, 64.3% of the low-dose patients and 43.8% of the high-dose subjects
      responded to treatment [>/=20% reduction in the Positive and Negative Syndrome
      Scale (PANSS) total score] ( P=0.018). In detail, the low-dose individuals were
      significantly superior in percentage changes in the PANSS total and general
      subscale scores at endpoint. The low-dose group also tended to improve more
      (albeit statistically insignificantly) in the PANSS positive and negative
      subscales and other efficacy measures. Compared to the patients with
      undifferentiated subtype, those with disorganized subtype received higher dosage
      by 0.90 mg/day, after controlling for other variables ( P=0.008). Paranoid
      subtype was similar to undifferentiated subtype in drug doses. Patients with
      longer illness duration also showed a trend to use higher dosage ( P=0.078).
      CONCLUSIONS: These findings suggest that dosage adjustment to diminish side
      effects does not compromise risperidone response and that disorganized patients
      and perhaps patients with longer illness duration are prone to receive larger
      doses.

PMID- 14663552
TI  - Eye movements to smoking-related cues: effects of nicotine deprivation.
AB  - RATIONALE: According to recent theories of addiction, nicotine deprivation may
      influence biases in the orienting and maintenance of attention on smoking-related
      cues. OBJECTIVES: We examined the effect of nicotine deprivation on different
      aspects of attentional biases for smoking-related cues. METHODS: Smokers' eye
      movements to smoking-related and control pictures were assessed during a visual
      probe task under deprived and non-deprived conditions. RESULTS: When deprived,
      smokers maintained their gaze for longer on smoking-related than control cues,
      relative to when non-deprived. Deprivation also increased craving and
      pleasantness ratings of smoking cues. Across both deprived and non-deprived
      conditions, smokers were more likely to shift their gaze towards smoking cues and
      were faster to respond to probes replacing smoking cues, relative to non-smoking
      cues, but these attentional bias measures were not significantly affected by the
      deprivation manipulation. CONCLUSIONS: Results suggest a selective effect of
      deprivation on the maintenance of attention on smoking-related cues.

PMID- 14663553
TI  - Combined low dose treatment with opioid and cannabinoid receptor antagonists
      synergistically reduces the motivation to consume alcohol in rats.
AB  - RATIONALE: Opioid and cannabinoid CB(1) receptor antagonists reduce the
      motivation to consume alcohol when taken individually but their effectiveness in
      combination is not yet known. OBJECTIVE: The effects of naloxone/naltrexone and
      SR 141716 alone and in combination were examined on beer consumption in rats.
      METHODS: In a progressive ratio paradigm rats were trained to lick at a tube for
      either beer (4.5% ethanol v/v) or near-beer (beer containing <0.5% ethanol v/v)
      under a progressive ratio schedule of reinforcement. They were then tested with
      naloxone (0.3, 0.6 or 1.2 mg/kg i.p.), SR 141716 (0.15, 0.3 or 0.6 mg/kg i.p.)
      and their combination. In a continuous access paradigm, other rats were given
      beer or near-beer in their home cages for several weeks and the effects of
      repeated (4 day) administration of naltrexone (0.3, 0.6 or 1.2 mg/kg), SR 141716
      (0.15, 0.3 or 0.6 mg/kg) and their combination were assessed. RESULTS: In the
      progressive ratio paradigm SR 141716, naloxone and their combination were more
      effective in reducing the break points for beer rather than near-beer. The two
      lowest dose combinations produced a synergistic reduction in break points. The
      highest dose combination reduced break points for both beer and near-beer and
      effects were more additive than synergistic. In the continuous access paradigm,
      the low doses of the drugs selectively reduced beer consumption in a synergistic
      fashion with higher doses having a less selective and more additive effect.
      CONCLUSIONS: The combined, low dose treatment has possible clinical efficacy in
      treating alcohol craving in humans.

PMID- 14663554
TI  - Inhibitory effect of resveratrol on angiotensin II-induced cardiomyocyte
      hypertrophy.
AB  - Resveratrol is proposed to account in part for the protective effect of red wine
      on the cardiovascular system. Angiotensin II (Ang II) is a potent hypertrophic
      stimulus in cardiomyocytes. In this study, we determined the effect of
      resveratrol on Ang II-induced cardiomyocyte hypertrophy. Cultured neonatal rat
      cardiomyocytes were stimulated with Ang II, and [3H]leucine incorporation and
      beta-myosin heavy chain (beta-MyHC) promoter activity were examined.
      Intracellular reactive oxygen species (ROS) were measured by a redox-sensitive
      fluorescent dye, 2' 7'-dichlorofluorescin diacetate, and the extracellular signal
      regulated kinase (ERK) phosphorylation was examined by Western blotting.
      Resveratrol inhibited Ang II-increased intracellular ROS levels. Furthermore,
      resveratrol, as well as the antioxidant N-acetyl-cysteine, decreased Ang II- or
      H2O2-increased protein synthesis, beta-MyHC promoter activity, and ERK
      phosphorylation. In summary, we demonstrate for the first time that resveratrol
      inhibits Ang II-induced cardiomyocyte hypertrophy via attenuation of ROS
      generation.

PMID- 14663558
TI  - Genetic analysis of in vitro shoot regeneration from cotyledonary petioles of
      Brassica oleracea.
AB  - Diallel analysis was used to investigate the genetic control of in vitro shoot
      regeneration in Brassica oleracea. Twelve doubled haploid (DH) lines, selected to
      include a range of genotypes with differing shoot regeneration potentials, were
      crossed reciprocally to produce 132 F(1) and 12 selfed, DH families. Cotyledonary
      petioles from 4-day-old seedlings, from all families, were excised and maintained
      on MS medium supplemented with 2 mg/l BAP. Explants were scored after 44 days for
      both the presence or absence of shoots and the number of regenerating shoots per
      explant. Diallel analysis showed both shoot regeneration and the production of
      multiple shoots to be controlled by additive and dominant gene effects, with
      additive effects being more important. Additive gene effects accounted for 71%
      and 77% of the genetic variation observed within the diallel for shoot
      regeneration and multiple shoot regeneration, respectively. By investigating the
      shoot regeneration potential of subsequent backcross and F(2) populations, the
      ability to introduce and increase shoot regeneration potential into otherwise
      recalcitrant lines was demonstrated.

PMID- 14663559
TI  - Molecular approaches to brain tumour invasion.
AB  - In glioma cells, the stimulatory input of extracellular matrix components and an
      increased sensitivity to growth factors result in a high proliferative and
      migratory behaviour. Cell surface receptor interactions play pivotal roles in
      converging information about conditions in the environment immediately outside
      the cell. The transduced signal, in turn induces a response within the cell that
      provokes a specific behaviour. Cellular migration and cell proliferation are
      interwoven processes that share several common intracellular pathways. The major
      cross-links are the phosphoinositol phosphate regulating enzymes, PI-3 kinase and
      PTEN, the focal adhesion kinase (FAK) and the tumour suppressor p53. An
      understanding of the interaction between the molecular participants involved in
      migration and proliferation will promote the design of new treatments. A full
      understanding of the basis of the invasiveness of tumour cells remains elusive.
      Gene and protein expression are being studied, using modern techniques such as
      microarray analysis, SAGE and 2-D protein gels. Transient and permanent protein
      protein interactions and recruitment of proteins to specialised cellular domains
      are equally important in regulating cellular invasion and presumably will attract
      more attention in future.

PMID- 14663560
TI  - Traumatic acute subdural haematomas of the posterior fossa: clinicoradiological
      analysis of 24 patients.
AB  - BACKGROUND: We report 24 patients with a traumatic acute subdural haematoma of
      the posterior fossa managed between 1997 and 1999 at 8 Italian neurosurgical
      centres. METHOD: Each centre provided data about patients' clinico-radiological
      findings, management, and outcomes, which were retrospectively reviewed.
      FINDINGS: A poor result occurred in 14 patients (58.3%). Ten patients (41.7%) had
      favourable results. Patients were divided into two groups according to their
      admission Glasgow Coma Scale (GCS) scores. In Group 1 (12/24 cases; GCS score, >
      or =8), the outcome was favourable in 75% of cases. In Group 2 (12/12 cases; GCS
      score, <8), the outcome was poor in 91.6% of cases. Nineteen patients underwent
      posterior fossa surgery. Factors correlating to outcome were GCS score, status of
      the basal cisterns and the fourth ventricle, and the presence of supratentorial
      hydrocephalus. Multivariate analysis showed significant independent prognostic
      effect only for GCS score (P<0.05). INTERPRETATION: acute posterior fossa
      subdural haematomas can be divided into two distinct groups: those patients
      admitted in a comatose state and those with a moderate/mild head injury on
      admission. Comatose patients present usually with signs of posterior fossa mass
      effect and have a high percentage of bad outcomes. On the contrary, patients
      admitted with a GCS of 8 or higher are expected to recover. In these patients the
      thickness of the haematoma (<1 cm) seems to be a guide to indicate surgical
      evacuation of the haematoma.

PMID- 14663561
TI  - Cerebral arteriovenous malformations: influence of angioarchitecture on bleeding
      risk.
AB  - BACKGROUND: To evaluate the angioarchitecture of cerebral arteriovenous
      malformations (cAVMs) with special regard to its influence on the risk of
      intracranial haemorrhage. METHODS: Clinical and neuroradiological data of 171
      patients with cAVMs, who were treated at our department, were analysed
      retrospectively. The angioarchitectonic data were obtained from angiographic
      series, cranial CT scans and MR images. A chi(2) test was conducted to correlate
      the parameters and determine the P values. FINDINGS: The following parameters
      correlate to an increased risk of haemorrhage: diameter of the nidus < or =2 cm
      (P<0.001), number of arterial feeders < or =2 (P<0.001), diameter of the main
      feeder < or =1 mm (P<0.0001), number of veins draining the nidus < or =2
      (P<0.001), exclusive deep drainage (P<0.05), and low or middle flow-velocity
      (P<0.01). Specific angioarchitectonic features such as venous stenoses, varicose
      dilatation of the draining vein, arterial aneurysms of the feeding artery,
      arteriovenous fistula within the nidus, contralateral drainage and sinushypo/
      aplasia did not alter the bleeding rate. INTERPRETATION: Various angiographic
      features were correlated with the occurrence of intracranial haemorrhage in
      patients with cerebral AVMs. In addition to the well-known factors influencing
      the bleeding risk of cAVMs like size, pattern of venous drainage and location
      within the brain our data demonstrate the importance to look at the diameter of
      the main feeder and the number of draining veins showing a better correlation.

PMID- 14663562
TI  - Bilateral severe carotid artery stenosis or occlusion - cerebral autoregulation
      dynamics and collateral flow patterns.
AB  - BACKGROUND: Bilateral severe obstruction of the internal carotid artery is a
      hemodynamically critical state. We aimed to (1) analyze dynamic cerebral
      autoregulation (DCA) in affected patients, and (2) to correlate DCA data with
      different collateral flow patterns. METHODS: DCA was assessed noninvasively by
      transfer function analysis (phase shift) of respiratory-induced oscillations at
      0.1 Hz of arterial blood pressure (Finapres method) and cerebral blood flow
      velocity (transcranial Doppler) in 30 patients with severe bilateral carotid
      stenosis (> or =75%) or occlusion. CO(2)-reactivity was measured via inhalation
      of 7% CO(2). 30 patients with unilateral stenosis were recruited as controls.
      RESULTS: Patients with bilateral 75-89% stenosis had a virtually preserved phase
      shift. A pronounced reduction was found in bilateral critical stenosis or
      obstruction (90-100%). Patients with ipsilateral 90-100% and contralateral 75-89%
      stenosis had a significantly less severe reduction of phase shift on the
      ipsilateral side. CO(2)-reactivity showed a less marked reduction in patients
      with bilateral critical stenosis or occlusion. Phase shift was best if
      "Willisian" collaterals were present. Significantly reduced values were found if
      only secondary collaterals (ophthalmic artery, leptomeningeal flow) were
      detected. Poorest values occurred with recruitment of functionally stenosed
      "Willisian" collaterals. CO(2)-reactivity showed poor values with sole
      recruitment of secondary collaterals, whereas functionally stenosed primary
      collaterals did not show values as poor as for phase shift. Clinically
      symptomatic patients had significantly lower phase shift and CO(2)-reactivity
      values. CONCLUSIONS: DCA is severely impaired in bilateral critical carotid
      stenosis or occlusion. Sole recruitment of secondary collaterals and signs of a
      functional stenosis in primary ("Willisian") collaterals reflect insufficient
      collateral supply with a poor hemodynamic status. CO(2)-reactivity assessing the
      vasodilatory reserve and DCA represent different information for characterizing
      cerebral hemodynamic impairment. Determining transfer function phase might be a
      physiologically well supported approach for analysis of cerebral hemodynamic
      compromise.

PMID- 14663563
TI  - Moyamoya disease and Moyamoya syndrome: experience in Europe; choice of
      revascularisation procedures.
AB  - OBJECTIVES: To present our clinical experience in terms of disease presentation
      and choice of revascularisation procedure in our first group of 23 European
      Moyamoya angiopathy (disease and syndrome) patients. METHOD AND PATIENT
      SELECTION: Twenty three patients were diagnosed and treated from 1997-2001 in our
      neurosurgical department. All patients underwent preoperative angiography, colour
      Doppler examination, cranial MRI and/or CT scans, HMPAO-SPECT or H(2)(15)O PET
      (baseline and Diamox challenge) scans. Nineteen patients presented with child
      juvenile Moyamoya angiopathy with an average age at presentation of 8 years
      (range 1-17 years), in 4 patients adult Moyamoya was diagnosed with a mean age at
      presentation of 34 years (range 23-40 years). RESULTS: In all but one patient
      bilateral affection was present at the time of diagnosis. All patients underwent
      direct and/or additional indirect revascularisation procedures. Twenty-one
      patients underwent bilateral revascularisation procedures. In two patients a
      unilateral procedure was performed. A direct STA-MCA bypass (superficial temporal
      artery branch - middle cerebral artery branch anastomosis) was performed in all
      patients. Additional direct STA-ACA bypass (STA - anterior cerebral artery branch
      anastomosis) was performed in 10 patients. Indirect arteriosynangiosis using the
      occipital artery was performed in the posterior cerebral artery (PCA) territory
      in 3 patients. The frontal branch of the STA was used for arteriosynangiosis in
      the frontal region in another 2 patients. Indirect frontal durasynangiosis was
      performed in 14 patients. The number and location of multiple revascularisation
      procedures was determined according to the angiographic findings as well as the
      site of decreased perfusion reserves seen on H(2)(15)O PET. A one stage
      revascularisation procedure was performed in 7 patients. Fourteen patients
      underwent two stage procedures. Following operation no complications were
      encountered in all but one adult patient who died postoperatively due to a
      massive middle cerebral artery infarct on the nonoperated side. CONCLUSIONS: As
      territorial hemodynamic disorder seems to be a characteristic in Moyamoya disease
      and/or syndrome, judging from our experience with European patients in our
      series, and several reports hitherto, treatment with multiple revascularisation
      procedures is considered to be justified.

PMID- 14663564
TI  - Ruptured intracranial dissecting aneurysms: management considerations with a
      focus on surgical and endovascular techniques to preserve arterial continuity.
AB  - BACKGROUND: The present retrospective analysis was undertaken to review an
      institutional experience with 13 intracranial dissecting aneurysms as source of
      subarachnoid haemorrhage (SAH) among a total of 585 ruptured intracranial
      aneurysms. METHODS AND RESULTS: In 6 patients the vertebral artery (VA) was
      affected, in 2 patients the basilar artery (BA), in 3 the internal carotid (ICA),
      in 1 the middle cerebral (MCA) and in 1 the postcommunicating (A2) segment of the
      anterior cerebral artery (ACA). Maintaining arterial patency was aimed at in all
      patients. Tangential clipping or circumferential wrapping were used as surgical
      methods. Endovascular stenting and/or coiling was applied in 2 instances. Four of
      the 6 VA dissecting aneurysms underwent surgical exploration between 1 and 22
      days after haemorrhage. Two patients were in WFNS grade V and died subsequently
      with the aneurysms untreated, one after rehaemorrhage. In the patients with
      secured VA aneurysms the postoperative course was uncomplicated with the
      exception of additional caudal cranial nerve injury in 1 instance. Both BA
      aneurysms were initially treated by endovascular methods. In the first patient
      incomplete packing with Gugliemi detachable (GDC) coils was achieved. Follow-up
      angiography 6 months later showed growth and coil compaction and subsequent
      wrapping with Teflon fibres resulting in angiographic stabilization. The other BA
      aneurysm was treated by a combination of a coronary stent and GDC coils. The 3
      dissecting ICA aneurysms were all explored surgically. In only 1 instance ICA
      continuity could be preserved by wrapping, in the other 2 cases a major portion
      of the vessel wall disintegrated upon removal of the surrounding clot. The only
      ACA dissecting aneurysm, on A2, was successfully treated with a Dacron cuff. In
      the single patient with a MCA aneurysm, a decision for conservative management
      was taken, because neither a surgical nor an endovascular solution was seen as a
      possibility that did not risk occlusion of lenticulostriate branches. The patient
      suffered a fatal rehaemorrhage 4 weeks later at her home. CONCLUSIONS: The
      reported experience suggests that in Western countries also dissecting aneurysms
      are an occasional source of SAH. The outcome in our conservatively managed
      patients confirms the poor prognosis of conservative management. Wrapping and
      endovascular stent based methods can achieve stabilization of the dissected
      artery without sacrificing the artery. Results of treatment appear to depend
      largely on the location of the dissecting aneurysm.

PMID- 14663565
TI  - Early antithrombotic prophylaxis with low molecular weight heparin in
      neurosurgery.
AB  - BACKGROUND: Despite the high risk of venous thromboembolic events (VTE) in neuro
      surgical patients, heparin prophylaxis has not been routinely established due to
      concern about bleeding complications. After initiating early low molecular weight
      heparin (LMWH) prophylaxis, we reviewed our patients in order to examine the
      viability of this practice. METHOD: Over a 3 year period, the records of patients
      admitted for elective neuro-surgery (ES), head injury (HI) or spontaneous
      intracranial haemorrhage (ICH) were analysed. Prophylaxis was performed with
      certoparin (3000 U anti-factor Xa s.c.) on the evening before ES and within 24
      hours after surgery or admission whenever a CT did not show a progressive
      haematoma. Contraindications for LMWH were prothrombin time <70%, partial thrombo
      plastin time >40 s, platelet count <100.000/ml, and platelet aggregation test sum
      <60%. The incidence of bleeding complications, VTE, and resulting
      morbidity/mortality was assessed. FINDINGS: 294 patients were admitted for ES,
      344 for HI, and 302 for ICH. 155 of these were excluded because of
      contraindications. Intracranial bleeding was recorded in 1.5% (ES 1.1%, HI 3.5%,
      ICH 0%) and operative revision was performed in 1.1% (ES 0.7%, HI 2.8%) of
      patients. One case of moderate disability and no mortality occurred. The
      incidence of VTE and pulmonary embolism was documented in 0.2% and 0.1% of
      patients, with no associated mortality. No heparin induced thrombocytopenia was
      observed. INTERPRETATION: In neurosurgical patients, antithrombotic prophylaxis
      with certoparin was determined to be safe and efficacious when contraindications
      are carefully considered and a 12-hour time interval before and after surgery was
      guaranteed. This retrospective analysis should encourage a prospective trial of
      early LMWH prophylaxis.

PMID- 14663566
TI  - Asymptomatic shunt malfunction detected fortuitously by observation of
      papilloedema.
AB  - Significant shunt malfunction is nearly always followed by headache, nausea,
      vomiting, lethargy and/or visual disturbances. In many cases there are also signs
      of raised intracranial pressure on computed tomography (CT). In six
      hydrocephalic, shunt dependent children (8-14,5 years) with no or slight symptoms
      shunt malfunction was detected because of papilloedema. The oedema was detected
      in three children at routine check up, in two at regular visual check up and in
      one at an ophthalmological examination because of slight headache. At
      neurological examination five had no new symptoms, but one was ataxic. In five
      patients a CT scan was done, three showed slight ventricular dilatation. Splayed
      sutures were found in two children. At shunt revision the measured intracranial
      pressure was increased, varying between 25-52 cm H(2)O. In five children the
      oedema disappeared after shunt-revision without any visual reduction, but in one
      the visual deficit did not improve. Older children can have shunt malfunction
      leading to increased intracranial pressure, with no or discrete symptoms and no
      obvious ventricular dilatation but with asymptomatic papilloedema. Ophthalmoscopy
      can therefore be of great value at routine check up in these children.

PMID- 14663567
TI  - The significance of gemistocytes in astrocytoma.
AB  - BACKGROUND: A retrospective clinical analysis of astrocytomas which contained a
      significant proportion of gemistocytes was carried out in order to evaluate their
      effect on prognosis, and other factors influencing prognosis. METHOD: From 253
      consecutive cases of astrocytic tumours in adults, 25 were selected who had more
      than 20% gemistocytes in every high-power field examined. 9 of these had
      anaplasia, the remainder did not. They were divided into two groups according to
      the proportion of gemistocytes; group A, contained more than 60% gemistocytes,
      and group B, had between 20 and 60% gemistocytes. TUNEL and immunohistochemical
      staining for PCNA, p53, Ki-67, bcl-2 were performed in the 20 available cases.
      FINDINGS: The median follow-up period was 46 months. There were 14 recurrences,
      with a median time to recurrence of 15 months. Thirteen repeat operations were
      performed in nine cases, and two cases showed recurring malignant transformation.
      The overall median survival time following diagnosis was 73 months and the 5-year
      survival rate was 52%. There were no significant differences in median survival
      between groups A and B with different proportions of gemistocytes. On the other
      hand the median survival of the gemistocytic astrocytomas with anaplasia was 25
      months, compared with 158 months for those without anaplasia (p=0.0005). The
      significant impact of anaplasia on survival persisted in both groups. There were
      no significant differences in immunohistochemical staining between the two
      groups, with the exception of staining for Ki-67 (means of the two groups: group
      A 1.40; group B 2.50). CONCLUSIONS: It is suggested that the proportion of
      gemistocytes does not itself affect prognosis.

PMID- 14663568
TI  - Laser Doppler flowmetry in non-human primate stroke studies: model refinement for
      pre-clinical development of cerebroprotective strategies.
AB  - BACKGROUND: Safety, feasibility, and efficacy trials in non-human primate stroke
      models are essential to the evaluation of experimental therapies and their
      translation to humans. Although Laser Doppler Flowmetry has been successfully
      employed in rodent stroke to continuously monitor cerebral blood flow, it has not
      been applied in primate studies. This investigation examined the utility of Laser
      Doppler Flowmetry in refining an existing baboon model of cerebral
      ischemia/reperfusion. METHOD: Continuous Laser Doppler Flowmetry monitoring was
      used, in non-human primates, to document local cerebral blood flow before,
      during, and after middle cerebral artery territory occlusion. In each baboon (n =
      7) a single Doppler probe was placed into the left frontal cortex through a
      precoronal burr hole. Correlations between Laser Doppler Flowmetry values and
      latencies to Motor Evoked Potential dropout were compared using a linear
      regression model. FINDINGS: Placement of the Laser Doppler probe was easily
      accomplished in all animals. Laser Doppler Flowmetry tracings accurately
      documented blood flow changes that occurred with each technical manipulation
      during the procedure. Laser Doppler confirmed decreased perfusion that coincided
      both regionally and temporally with vessel occlusion. Depth of ischemia as
      measured by Laser Doppler Flowmetry was associated with Motor Evoked Potential
      dropout latencies for individual animals. CONCLUSIONS: Continuous, single probe
      Laser Doppler Flowmetry is a reliable method of documenting perfusion changes
      following middle cerebral artery territory occlusion in a baboon model of
      reperfused stroke. This advanced intraoperative monitoring technique may lead to
      more accurate evaluation of acute stroke therapies in pre-clinical trials.

PMID- 14663569
TI  - A new subdural probe for combined intracranial pressure (ICP) and cerebral blood
      flow (CBF) monitoring.
AB  - We report the development of a new subdural probe for combined intracranial
      pressure (ICP) and cerebral blood flow (CBF) monitoring with near infrared
      spectroscopy (NIRS) and indocyanine green (ICG) dye dilution. For NIRS a
      conventional subdural ICP monitoring probe was supplied with two fiber bundles
      and 90-degree prisms. Injections of 25 mg ICG were performed. Regional values for
      the mean transit time of ICG (rmtt(ICG)), cerebral blood flow (rCBF) and cerebral
      blood volume (rCBV) were calculated. With prototypes of the probe in two patients
      with intracerebral haemorrhage 18 comparative measurements obtained
      simultaneously with conventional NIRS (optodes placed on the skin) and the
      subdural NIRS probe were performed. The new subdural NIRS probe allows combined
      monitoring of ICP and cerebral hemodynamics in the brain directly, without the
      influence of extracerebral tissue.

PMID- 14663570
TI  - Development and rupture of a de novo basilar artery aneurysm after surgical
      removal of a cerebellar arteriovenous malformation.
AB  - BACKGROUND: The de novo development of an aneurysm in an previously normal artery
      is an uncommon event. We describe a patient who developed a de novo bleeding
      aneurysm of the basilar artery in the three weeks following the surgical removal
      of a large cerebellar AVM. METHOD-FINDINGS: A 48-year-old man suddenly developed
      transient headache, vertigo and disturbance of balance. Neuroradiological
      examinations showed the presence of a large AVM of the right cerebellar
      hemisphere. The AVM was removed successfully; following the operation there were
      repeated bleeding episodes at the operating site, requiring surgical evacuation.
      Three weeks after the AVM removal he suffered from a massive subarachnoid
      haemorrhage due to the rupture of an aneurysm developed de novo in the basilar
      artery. INTERPRETATION: This is the first reported case, to our knowledge, of a
      de novo aneurysm developed in an artery hemodynamically related to a surgically
      removed AVM. This complication was probably due to the postoperative hemodynamic
      changes in the vessels afferent to the AVM, associated with arterial wall
      dysplasia.

PMID- 14663571
TI  - Aggressive management of orbital meningeal melanocytoma.
AB  - OBJECTIVE: Meningeal melanocytoma generally occurs in the posterior fossa.
      Orbital manifestation is rarely encountered. METHODS: A thirty-five year-old man
      presented with progressive proptosis of his right eye. Computed tomography (CT)
      and Magnetic Resonance Imaging (MRI) of the brain showed an expansive intraconal
      mass lesion occupying the superior orbital compartment, the entire orbital apex,
      and the optic foramen. Histological analysis and Immunohistochemical staining for
      S-100 and HMB-45 monoclonal antibodies confirmed melanocytoma. FINDINGS:
      Microsurgical removal was accomplished through a fronto-orbital craniotomy.
      Chemotherapy and irradiation followed the initial intervention. The patient
      returned for follow up two years after surgery, complaining of headache and right
      visual loss. A subfrontal tumor with massive edema was found on follow up CT
      scan. INTERPRETATION: Meningeal melanocytomas are rare benign pigmented tumors of
      the central nervous system. They are predominant in the posterior fossa and
      spinal cord and frequently mistaken for melanomas, especially on frozen sections.
      Orbital presentation is rare. The natural history is poorly defined.

PMID- 14663572
TI  - Plasma cell granuloma involving the brain and the lung.
AB  - BACKGROUND: Symptomatic plasma cell granulomas (PCG) of the central nervous
      system (CNS) are a rare entity, especially in association with an extracranial
      manifestation. CLINICAL PRESENTATION: A 13 years old boy was operated on for a
      symptomatic plasma cell granuloma of the lower lobe of the left lung. Four years
      later, he suffered his first generalized seizure. CT and MRI scans revealed a
      small hyperdense lesion, which was located in the right frontal lobe, adjacent to
      the motor strip. Intervention. Stereotactic guided surgery was performed. A
      plasma cell granuloma was found, which histopathologically resembled the
      intrapulmonary lesion, which had been removed four years ago. CONCLUSION:
      Histological findings, differential diagnosis and specific treatment are reviewed
      and discussed. Patients with PCG should be radiologically staged. Long term
      prognosis of PCG is good in cases surgically resectable. Nevertheless, patients
      require lifelong follow up.

PMID- 14663573
TI  - Late spontaneous cerebrospinal fluid fistula in inner ear dysplasia.

PMID- 14663574
TI  - Euroacademia Multidisciplinaria Neurotraumatologica. Abstracts for the 8th
      Congress in Graz, Austria, May 21-24, 2003.

PMID- 14663577
TI  - Genetic structure of a population of the ectomycorrhizal fungus Russula vinosa in
      subtropical woodlands in southwest China.
AB  - The genetic structure of a population of the ectomycorrhizal fungus Russula
      vinosa was analyzed using random amplified polymorphic DNA markers. Of 121 bands,
      114 (94.2%) were polymorphic and there was a high genetic diversity (H=34.98) in
      this population. Each sporocarp represented a different genet and the genet size
      was no larger than 1 m. Pairwise sporocarps closer than 10 m had significantly
      higher genetic similarity. Second-order analysis indicated clumps with a radius
      of about 20 m in the whole population as well as in three genetic groups, i.e.
      simple matching similarity coefficients (Sm) 0.5-0.6, 0.6-0.7, and 0.7-0.8,
      respectively. The high-genetic-similarity group tended to have small clumps with
      high density, whereas the low-genetic-similarity group tended to have large
      clumps with low density. The spatial pattern analysis showed that the population
      mainly spread by short-distance spore dispersal rather than vegetative growth of
      dicaryophytic mycelia or long-distance spore dispersal.

PMID- 14663578
TI  - Indigenous and introduced arbuscular mycorrhizal fungi contribute to plant growth
      in two agricultural soils from south-western Australia.
AB  - Arbuscular mycorrhizal (AM) fungi occur in all agricultural soils but it is not
      easy to assess the contribution they make to plant growth under field conditions.
      Several approaches have been used to investigate this, including the comparison
      of plant growth in the presence or absence of naturally occurring AM fungi
      following soil fumigation or application of fungicides. However, treatments such
      as these may change soil characteristics other than factors directly involving AM
      fungi and lead to difficulties in identifying the reason for changes in plant
      growth. In a glasshouse experiment, we assessed the contribution of indigenous AM
      fungi to growth of subterranean clover in undisturbed cores of soil from two
      agricultural field sites (a cropped agricultural field at South Carrabin and a
      low input pasture at Westdale). We used the approach of estimating the benefit of
      AM fungi by comparing the curvature coefficients (C) of the Mitscherlich equation
      for subterranean clover grown in untreated field soil, in field soil into which
      inoculum of Glomus invermaium was added and in soil fumigated with methyl
      bromide. It was only possible to estimate the benefit of mycorrhizas using this
      approach for one soil (Westdale) because it was the only soil for which a
      Mitscherlich response to the application of a range of P levels was obtained. The
      mycorrhizal benefit (C of mycorrhizal vs. non-mycorrhizal plants or C of
      inoculated vs. uninoculated plants) of the indigenous fungi corresponded with a
      requirement for phosphate by plants that were colonised by AM fungi already
      present in the soil equivalent to half that required by non-mycorrhizal plants.
      This benefit was independent of the plant-available P in the soil. There was no
      additional benefit of inoculation on plant growth other than that due to
      increased P uptake. Indigenous AM fungi were present in both soils and colonised
      a high proportion of roots in both soils. There was a higher diversity of
      morphotypes of mycorrhizal fungi in roots of plants grown in the Westdale soil
      than in the South Carrabin soil that had a history of high phosphate fertilizer
      use in the field. Inoculation with G. invermaium did not increase the level of
      colonisation of roots by mycorrhizal fungi in either soil, but it replaced
      approximately 20% of the root length colonised by the indigenous fungi in
      Westdale soil at all levels of applied P. The proportion of colonised root length
      replaced by G. invermaium in South Carrabin soil varied with the level of
      application of P to the soil; it was higher at intermediate levels of recently
      added soil P.

PMID- 14663579
TI  - Suggested management of immunocompromized kidney patients suffering from SARS.
AB  - The treatment of severe acute respiratory syndrome (SARS) is still empirical and
      controversial. Herein we report our experience in treating approximately 40 SARS
      children and adolescents. Treatment of SARS kidney patients is limited.
      Paediatric nephrologists should be on the alert for SARS in order to care for
      immunocompromised patients. Precautions should be made for both staff and
      patients with protective measures for infection control.

PMID- 14663582
TI  - Toxoplasma gondii: changes of transepithelial ion transport in infected HT29/B6
      cell monolayers.
AB  - An in vitro system was established to study the effect of coccidian parasites on
      ion transport systems in epithelial tissues using HT29/B6, a human colon
      carcinoma cell line, and Toxoplasma gondii as a model parasite. Ion transport was
      measured in perfusion chambers 5, 10 and 15 h post-infection using monolayers in
      which approximately 30% of the cells were parasitized. The infection had rapid
      effects on the conductance and unidirectional chloride fluxes of infected cell
      monolayers, which were two to three times higher than those of uninfected HT29/B6
      cell monolayers throughout the observation period. However, the chloride net
      fluxes and short-circuit current were unaffected by the parasites, while the
      decrease of chloride seromucosal fluxes and conductance after addition of
      bumetanide were affected by the infection. The unidirectional mannitol fluxes,
      which correspond with water motion through paracellular pathways, were increased
      in infected HT29/B6 cell monolayers.

PMID- 14663583
TI  - The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene
      mutations in endometrial carcinoma.
AB  - PURPOSE: To evaluate the frequency of ERBB2, INT2 and CMYC oncogene
      amplifications and their coexistence with PTEN gene mutations in endometrial
      carcinomas. METHODS: In 54 endometrial carcinomas amplification of ERBB2, INT2
      and CMYC was determined using differential polymerase chain reaction (dPCR), and
      mutations in all exons of PTEN were investigated by PCR-SSCP and direct
      sequencing methods. Results were correlated with clinicopathological features of
      tumors. RESULTS: In 31 out of 54 endometrial carcinomas (57.4%) genetic defects
      were found within the examined genes. Of all identified defects, mutations in
      PTEN and the amplification of CMYC were most frequent (26/54-48.1% and 10/54
      18.5%, respectively). INT2 was amplified in 5.6% (3/54) of cases. In no case did
      we find ERBB2 amplification. In 77.4% (24/31) of cases only one gene was damaged.
      Of these, 20 cases showed only PTEN mutations, three cases only CMYC, and one
      case only INT2 amplification. In another seven out of 31 tumors (22.5%) defects
      in two or three genes coexisted simultaneously: PTEN and CMYC in five cases, CMYC
      and INT2 in one case, and PTEN, CMYC, and INT2 in one case. We found a number of
      interesting relations between the location of mutations within the PTEN sequence
      and the presence (+) or lack (-) of CMYC amplification. In the PTEN+CMYC- tumors
      the PTEN mutations were most frequent in exons 1-5, and less frequent in exons 7
      8 (66.7% and 33.3%, respectively). In contrast, in the PTEN+CMYC+ carcinomas the
      PTEN mutations were found mainly in exons 7-8 (85.7%). PTEN mutations were
      equally frequent in both early and more advanced endometrial carcinomas. The CMYC
      amplification, however, was more frequent in advanced as compared to early
      tumors, although this difference did not reach statistical significance.
      CONCLUSIONS: Our data suggest that differences in the presence of genetic defects
      may reflect the different molecular pathways of endometrial carcinogenesis. These
      data also suggest that location of intragenic PTEN mutations and their
      coexistence with the CMYC amplification may play a crucial part in the
      development of various subtypes of endometrial carcinoma, but this preliminary
      suggestion requires further research.

PMID- 14663584
TI  - Cellular and whole-plant chloride dynamics in barley: insights into chloride
      nitrogen interactions and salinity responses.
AB  - The first analysis of chloride fluxes and compartmentation in a non-excised plant
      system is presented, examining ten ecologically pertinent conditions. The short
      lived radiotracer couple (38)Cl/(39)Cl was used as a Cl(-) tracer in intact
      barley ( Hordeum vulgare L. cv. Klondike) seedlings, which were cultured and
      investigated under four external [Cl(-)], from abundant (0.1 mM) to potentially
      toxic (100 mM). Chloride-nitrogen interactions were investigated by varying N
      source (NO(3)(-) or NH(4)(+)) and strength (0.1 or 10 mM), in order to examine,
      at the subcellular compartmentation level, the antagonism, previously documented
      at the influx level, between Cl(-) and NO(3)(-), and the potential role of Cl(-)
      as a counterion for NH(4)(+) under conditions in which cytosolic [NH(4)(+)] is
      excessive. Cytosolic [Cl(-)] increased with external [Cl(-)] from 6 mM to 360 mM.
      Cl(-) influx, fluxes to vacuole and shoot, and, in particular, efflux to the
      external medium, also increased along this gradient. Efflux reached 90% of influx
      at the highest external [Cl(-)]. Half-times of cytosolic Cl(-) exchange decreased
      between high-affinity and low-affinity influx conditions. The relationship
      between cytosolic [Cl(-)] and shoot flux indicated the presence of a saturable
      low-affinity transport system ("SLATS") responsible for xylem loading of Cl(-). N
      source strongly influenced Cl(-) flux to the vacuole, and moderately influenced
      Cl(-) influx and shoot flux, whereas efflux and half-time were insensitive to N
      source. Cytosolic pool sizes were not strongly or consistently influenced by N
      source, indicating the low potential for Cl(-) to act as a counterion to
      hyperaccumulating NH(4)(+). We discuss our results in relation to salinity
      responses in cereals.

PMID- 14663585
TI  - Dormancy termination of western white pine (Pinus monticola Dougl. Ex D. Don)
      seeds is associated with changes in abscisic acid metabolism.
AB  - Western white pine (Pinus monticola) seeds exhibit deep dormancy at maturity and
      seed populations require several months of moist chilling to reach their
      uppermost germination capacities. Abscisic acid (ABA) and its metabolites,
      phaseic acid (PA), dihydrophaseic acid (DPA), 7'-hydroxy ABA (7'OH ABA) and ABA
      glucose ester (ABA-GE), were quantified in western white pine seeds during
      dormancy breakage (moist chilling) and germination using an HPLC-tandem mass
      spectrometry method with multiple reaction monitoring and internal standards
      incorporating deuterium-labeled analogs. In the seed coat, ABA and metabolite
      levels were high in dry seeds, but declined precipitously during the pre-moist
      chilling water soak to relatively low levels thereafter. In the embryo and
      megagametophyte, ABA levels decreased significantly during moist chilling,
      coincident with an increase in the germination capacity of seeds. ABA catabolism
      occurred via several routes, depending on the stage and the seed tissue. Moist
      chilling of seeds led to increases in PA and DPA levels in both the embryo and
      megagametophyte. Within the embryo, 7'OH ABA and ABA-GE also accumulated during
      moist chilling; however, 7'OH ABA peaked early in germination. Changes in ABA
      flux, i.e. shifts in the ratio between biosynthesis and catabolism, occurred at
      three distinct stages during the transition from dormant seed to seedling. During
      moist chilling, the relative rate of ABA catabolism exceeded ABA biosynthesis.
      This trend became even more pronounced during germination, and germination was
      also accompanied by a decrease in the ABA catabolites DPA and PA, presumably as a
      result of their further metabolism and/or leaching/transport. The transition from
      germination to post-germinative growth was accompanied by a shift toward ABA
      biosynthesis. Dormant imbibed seeds, kept in warm moist conditions for 30 days
      (after an initial 13 days of soaking), maintained high ABA levels, while the
      amounts of PA, 7'OH ABA, and DPA decreased or remained at steady-state levels.
      Thus, in the absence of conditions required to break dormancy there were no net
      changes in ABA biosynthesis and catabolism.

PMID- 14663586
TI  - Are NADP-dependent isocitrate dehydrogenases and ferredoxin-dependent glutamate
      synthase co-regulated by the same photoreceptors?
AB  - Activities of NADP-dependent isocitrate dehydrogenases (cytosolic and plastidic
      isoforms, ICDH1 and ICDH2; EC 1.1.1.42) and ferredoxin-dependent glutamate
      synthase (Fd-GOGAT; EC 1.4.7.1) in turions of Spirodela polyrhiza were all
      stimulated by light. Single or repeated red light (R) pulses induced the activity
      of the enzymes and this effect was reverted by subsequent far-red light (FR)
      pulses. The enzymes are, therefore, co-regulated by the low-fluence response of
      phytochrome. For ICDH, this is reported here for the first time. Neither an
      effect of the very low-fluence response nor of the FR-mediated high-irradiance
      response was detectable. Irradiance with continuous R resulted in enhanced enzyme
      activities and protein levels (Western analysis using polyclonal antibodies
      against ICDH1 and Fd-GOGAT). These additional effects of continuous R (called a
      "non-induction effect") could be inhibited for ICDH1 and ICDH2 by the inhibitor
      of photosynthetic electron transport, 3-(3',4'-dichlorophenyl)-1,1-dimethylurea,
      and are therefore related to the effect of photosynthesis. In contrast, the non
      induction effect of Fd-GOGAT was resistant against this inhibitor. Moreover,
      hourly R pulses did not replace the effect of continuous R. The non-induction
      effect of light on the activity and protein level of Fd-GOGAT was therefore
      tentatively classified as an R-mediated high-irradiance response. The activity of
      Fd-GOGAT but not that of ICDHs was additionally regulated by a specific blue
      light receptor. It can be concluded that the levels of ICDHs and Fd-GOGAT were
      coordinated by light but were not co-regulated by the same photoreceptors.
      Nitrate is necessary for the light regulation of both enzymes, contributing to
      the coordinated expression of the relevant genes.

PMID- 14663587
TI  - Biological monitoring of workers exposed to N, N-dimethylformamide in synthetic
      leather manufacturing factories in Korea.
AB  - OBJECTIVES: To investigate the relationship between N, N-dimethylformamide (DMF)
      exposure and excretion of urinary N-acetyl- S-( N-methylcarbamoyl)cysteine (AMCC)
      and N-methylformamide (NMF) in workers at synthetic leather manufacturing
      factories in Korea, for the first time. METHODS: One-hundred forty-four male
      workers at nine synthetic leather manufacturing factories were surveyed. Exposure
      to DMF was evaluated through breathing zone air sampling followed by analysis via
      a gas chromatograph equipped with a flame ionization detector (GC-FID). The
      levels of NMF and AMCC were determined by a GC with a flame thermionic detector
      (GC-FTD). Urine samples were collected at the end of the workshift. RESULTS AND
      CONCLUSIONS: Geometric mean of workplace air DMF and urinary NMF was 8.8 ppm and
      47.5 mg/l, respectively, and the level of DMF and NMF was significantly
      correlated. The biological exposure limit for NMF (15 mg/ml) was exceeded in
      89.5% of urine samples, and 37.9% of air samples exceeded the environmental DMF
      exposure limit (10 ppm), indicating a serious health risk to the employees of the
      synthetic leather industry in Korea. Exposure to 10 ppm DMF in the workplace air
      corresponded to a urinary NMF concentration of 53.4 mg/l. Alcohol intake the day
      before urine was sampled influenced NMF excretion into urine (40.5 mg/l NMF for
      the no-alcohol group and 94.6 mg/l for the group consuming more than 63.0 g
      alcohol/day). We could not find a significant relationship between air DMF and
      urinary AMCC concentration. Exposure to 10 ppm DMF corresponded to an AMCC
      concentration of 8.0 mg/l in the urine samples collected on the same day as the
      air was sampled.

PMID- 14663588
TI  - Temporal and spatial dimensions of postnatal growth of the mouse urinary bladder
      urothelium.
AB  - Postnatal growth and renewal of mouse urothelium start on the day of birth. In
      the present study, temporal and spatial dimensions of urothelial growth were
      studied during the first two postnatal weeks. Quantitative analysis showed that
      the rate of urothelial cell proliferation is significantly higher during all 14
      postnatal days than in adult mice. Three peaks of proliferative and mitotic
      activity were revealed: on the day of birth and postnatal day 1, on days 6 and 7,
      and on day 14. The high proliferation rate around the day of birth and at
      postnatal days 6 and 7 coincides with cell death in the urothelium.
      Semiquantitative analysis showed that during all 14 postnatal days, the
      urothelial proliferative response is mostly confined to the basal cell layer.
      Urothelial cells divide predominantly in parallel to the plain of the urothelium
      on all chosen postnatal days. Increased portions of urothelial cells, dividing
      perpendicularly to the urothelium were observed only on the day of birth and on
      postnatal day 7. Our results suggest that postnatal growth of mouse urothelium is
      particularly the result of an increasing number of cells in individual cell
      layers and not the result of an increasing number of cell layers.

PMID- 14663589
TI  - Pattern of lipofuscin pigmentation in nitrergic and non-nitrergic, neurofilament
      immunoreactive myenteric neuron types of human small intestine.
AB  - Lipofuscin, an autofluorescent age pigment, occurs in enteric neurons. Due to its
      broad excitation and emission spectra, it overlaps with commonly used
      fluorophores in immunohistochemistry. We investigated the pattern of lipofuscin
      pigmentation in neurofilament (NF)-reactive nitrergic and non-nitrergic human
      myenteric neuron types. Subsequently, we tested two methods for reduction of
      lipofuscin-like autofluorescence. Myenteric plexus/longitudinal muscle
      wholemounts of small intestines of five patients undergoing surgery for carcinoma
      (aged between 18 and 69 years) were double stained for NF and neuronal nitric
      oxide synthase (nNOS). Lipofuscin pigmentation patterns were semiquantitatively
      evaluated by using confocal laser scanning microscopy with three different
      excitation wave lengths (one for undisturbed lipofuscin autofluorescence and two
      for specific labellings). Two pigmentation patterns could be detected in the five
      NF-reactive neuron types investigated. In nitrergic/spiny as well as in non
      nitrergic/stubby neurons, coarse, intensely autofluorescent pigment granules were
      prominent. In non-nitrergic type II, III and V neurons, a fine granular,
      diffusely distributed and less intensely autofluorescent pigment was obvious.
      After incubation of wholemounts in either CuSO(4) or Sudan black B solutions,
      unspecific autofluorescence could be substantially reduced whereas specific NF
      and nNOS fluorescence remained largely unaffected. We conclude that NF
      immunohistochemistry is useful for morphological representation of subpopulations
      of human myenteric neurons. The lipofuscin pigmentation in human myenteric
      neurons reveals at least two different patterns which can be related to distinct
      neuron types. Incubations of multiply stained whole mounts in both CuSO(4) or
      Sudan black B are suitable methods for reducing autofluorescence thus
      facilitating discrimination between specific (immunohistochemical) and non
      specific (lipofuscin) fluorescence.

PMID- 14663590
TI  - EBV-induced polymorphic lymphoproliferative disorder of the iris after heart
      transplantation.
AB  - BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) of the iris
      is a rare entity with only ten cases having been published as yet. Its clinical
      aspect is typical. Therapy is multimodal and affords an interdisciplinary
      approach. METHODS: A 7-year-old boy developed a lymphoproliferative mass of the
      iris with uveitis 4 years after heart transplantation and immunosuppression. A
      progressive, flesh-colored thickening of the iris with secondary angle closure
      glaucoma necessitated a diagnostic and therapeutic iridectomy. Morphological
      investigation of the iris specimen disclosed a polymorphic posttransplantation
      lymphoproliferative disorder (PTLD) and the presence of Epstein-Barr virus (EBV)
      within the tissue. The EBV load in peripheral blood monocytes was massively
      elevated, thus indicating a chronic EBV infection. After conservative treatment
      and radiation therapy, the iris mass quickly resolved. There was no evidence of
      systemic PTLD. CONCLUSIONS: PTLD is a well-known, EBV-induced entity that rarely
      affects the eye. EBV is principally detectable in specimens of iris PTLD. If
      conservative, antiviral treatment fails, the iris lesions can be treated by local
      radiation therapy with very good success. In the near future, patients with PTLD
      of the eye may benefit from immunologic treatment with ex vivo generation of
      virus-specific T-lymphocytes.

PMID- 14663591
TI  - Stereoscopic visual evoked potentials in normal subjects and patients with open
      angle glaucomas.
AB  - PURPOSE: To evaluate stereoscopic visual evoked potentials (S-VEP) in normal
      controls and in patients with glaucomatous optic nerve damage. METHODS: Computer
      generated dynamic random-dot stereograms were used to elicit cortical visual
      evoked potentials using wireless electric liquid crystal shutter glasses. Normal
      subjects (n=22) and patients with glaucoma (n=22) were investigated using five
      different disparities from 9 to 40 arc min. Statistical dependency of
      measurements with different stimulus at identical patients was adjusted for.
      RESULTS: Peak times of onset and offset response of S-VEP can be significantly
      delayed in glaucomas. A general linear regression model confirmed that
      differences between patients and normals depend on disparity. S-VEP onset shows
      no significant difference between controls and glaucomas at 9 arc min disparity.
      At high disparities, however, peak time of the onset response was significantly
      (p<0.01) delayed in glaucomas when compared with normals (normals: 125.8+/-13 ms,
      glaucomas: 148.2+/-25.6 ms at 40 arc min). CONCLUSIONS: Visual evoked potential
      elicited by the onset of a random-dot stereogram can be used for objective
      measurement of stereoacuity in a clinical setting. Differences between controls
      and glaucomas in high and low disparities could indicate a stereo-specific
      deficit in glaucoma.

PMID- 14663592
TI  - Color Doppler imaging in ocular hypertension and open-angle glaucoma.
AB  - PURPOSE: To quantify the retrobulbar hemodynamics of patients with ocular
      hypertension and open-angle glaucoma and to compare it with that of normal
      subjects. METHODS: Nineteen eyes of 19 ocular hypertensive patients, 19 eyes of
      19 open-angle glaucoma patients and 19 eyes of 19 normal subjects were recruited
      from our clinic and underwent color Doppler imaging evaluation of the ophthalmic,
      posterior ciliary, and central retinal arteries. The peak systolic and end
      diastolic blood flow velocities and resistivity indices of all retrobulbar
      vessels were measured. RESULTS: The retrobulbar blood flow velocities were lower
      and resistivity indices were higher in all retrobulbar vessels in ocular
      hypertensive patients than in normal subjects. The differences, however, did not
      reach statistical significance ( P>0.05). Glaucoma patients had lower end
      diastolic velocities and higher resistivity indices than did normal subjects in
      the ophthalmic ( P=0.003 and P=0.003, respectively), posterior ciliary ( P=0.001
      and P<0.001, respectively), and central retinal arteries ( P=0.03 and P=0.04,
      respectively). Glaucoma patients had significantly lower end-diastolic velocity
      and higher resistivity index than did patients with ocular hypertension in the
      posterior ciliary artery ( P=0.04 and P=0.001, respectively). CONCLUSIONS: This
      study suggests that ocular hypertensive patients have more normal blood flow than
      do glaucoma patients, because all retrobulbar homodynamic measurements in ocular
      hypertension range between glaucoma and normal subjects. On the other hand,
      glaucoma is associated with blood-flow velocity reduction and resistivity index
      elevation in all retrobulbar arteries.

PMID- 14663593
TI  - Ageing of the retinal pigment epithelium: implications for transplantation.
AB  - This review will discuss some of the implications for using cells from aged
      donors for retinal pigment epithelium (RPE) transplantation. It will consider age
      related changes in the structure and function of RPE cells and the accumulation
      of potentially damaging photoreactive constituents. The review will focus on the
      role of the ocular pigments lipofuscin and melanin in respect to age-related
      changes in composition, photoreactivity and potential role in retinal ageing and
      age-related macular degeneration. The article concludes by considering the
      suitability of senescent RPE cells for transplantation and whether such cells can
      be rejuvenated.

PMID- 14663594
TI  - Clinical variables and their relation to visual outcome after vitrectomy in eyes
      with diabetic retinal traction detachment.
AB  - BACKGROUND: To analyse vitrectomy results in diabetic eyes with retinal traction
      detachment and to investigate which variables are associated with a worse visual
      outcome. METHODS: Forty-four diabetic eyes (33 patients) with central retinal
      traction detachment were analyzed retrospectively. RESULTS: After a median follow
      up of 10 months, median visual acuity significantly improved from 20/800 to
      20/160 (P=0.02), despite the fact that the majority of patients had a long
      standing macular traction detachment (median 120 days). Twenty-two eyes (50%)
      achieved a visual acuity of >20/200. The retina was finally reattached in 38 eyes
      (86.3%). Univariate analysis showed that patients with type 2 diabetes, age older
      than 50 years, preoperative visual acuity <20/200, iris neovascularisation and
      macular detachment of >30 days had a significantly worse final visual outcome.
      After multiple logistic regression analysis, age and iris neovascularisation were
      the strongest predictors of a worse visual outcome; if both were present, the
      chance of a obtaining a visual outcome of <20/200 was almost 90%. CONCLUSIONS:
      Age and iris neovascularisation were the strongest predictors for a low visual
      outcome. In a review of vitrectomy studies in eyes with severe diabetic traction
      detachment in the past 2 decades, we found a trend towards higher anatomic
      success rates, while visual outcome only slightly improved. The current study
      confirmed the importance of ophthalmic variables, but also indicates the
      importance of evaluating systemic variables in larger series in order to predict
      which eyes may truly benefit from vitrectomy.

PMID- 14663595
TI  - Partially fluorinated alkanes as wash out solutions after removal of silicone oil
      used as an ocular endotamponade.
AB  - BACKGROUND: The partially fluorinated alkanes perfluorohexyloctane (F(6)H(8)) and
      perfluorobutylbutane (O(44 V)) were investigated as wash out solutions after
      routine silicone oil removal. METHODS: Eleven eyes were rinsed twice with
      F(6)H(8) immediately after passive silicone oil removal. The silicone oil
      concentration in both F(6)H(8) samples was measured quantitatively using optical
      emission spectroscopy (OES). Nine eyes were rinsed twice with O(44 V) immediately
      after passive silicone oil removal. The silicone oil concentration in both O(44
      V) samples was measured quantitatively using OES (n=5) and/or infrared
      spectroscopy (IR) (n=8). RESULTS: The mean concentration in the first F(6)H(8)
      sample was 103.0 ppm, and in the second sample 63.5 ppm using OES. The mean
      concentration in the first O(44 V) sample was 135.6 ppm, and in the second O(44
      V) sample 68.0 ppm using OES. CONCLUSION: Since the solubility of silicone oil in
      F(6)H(8) or O(44 V) is dependent on the temperature and mixture ratio, their use
      as a routine washout after silicone oil removal in patients without severe
      emulsification is inefficient. The degree of washout is strongly influenced by
      surface phenomena and adhesion forces.

PMID- 14663596
TI  - [Heparin-induced extracorporeal LDL precipitation (H.E.L.P.)].
AB  - The H.E.L.P procedure (heparin-induced extracorporeal LDL precipitation) is a
      selective and sophisticated apheresis procedure. By means of heparin and lowering
      the pH level, lipoproteins and fibrinogen are reduced by 50-60%. In addition to
      lipoprotein (a) reduction (50- 60%) adhesion molecules (ICAM- 1, VCAM-1, P
      selectin), which play a major role in the development and progression of
      atherosclerosis, are significantly lowered. Within 20 hours after LDL apheresis,
      positron emission tomography was able to verify an improvement of coronary
      vasodilation capacity. This is likely to result from a considerable reduction of
      LDL cholesterol and fibrinogen with a consecutive improvement of both endothelial
      function and rheology.

PMID- 14663597
TI  - [LDL-apheresis in the treatment of coronary heart disease. Rationale for a
      specific adjuvant therapy].
AB  - Coronary artery disease (CHD) still remains the leading cause of death in all
      industrialized countries. In Germany, it claims the lives of an estimated 220,000
      men and women and causes 200,000 non-lethal AMI's each year. Inspite of great
      efforts in the last 30 years, 25% of men and 40% of women still die within 12
      months after they preliminary survived their first myocardial infarction. The
      total direct plus indirect expenses for CHD in the year 2000 sum up to
      approximately 57 billion Euro in Germany and to 100 billion US $ in the US. To
      date, management of coronary artery disease still consists mainly of a therapy
      designed to improve blood flow and oxygen supply to the heart or to reduce
      myocardial oxygen consumption. On this line angioplasty, bypass surgery, and more
      recently stenting of coronary arteries, have become leading techniques, but only
      a minority (<50%) of patients at risk for CHD received therapy to change the
      atherosclerotic process itself. However, only by means of a causal intervention
      with the pathmaker mechanism of atherosclerosis can we expect to decrease the
      financial burden of CHD. No question, one of the leading causal factors for early
      atherosclerosis and coronary heart disease is the abundance of LDL cholesterol in
      the blood, exceeding limits of 100 mg/dl. Thus, recommendations for therapy focus
      on LDL levels less than 100 mg/dl. With the introduction of the statins-a family
      of very potent lipid lowering agents-such target levels can be achieved in most
      patients, resulting in a drastic decrease of LDL concentrations, as well as in a
      reduction of cardiac and total mortality. There is, however, a remaining small
      group of patients, who are more or less resistant to an adequate combination of
      dietary and drug therapy. For these patients, various techniques of apheresis
      have been available for over 15 years. Some of them, e. g., H.E.L.P. System,
      KANEKA System, have been approved by the FDA in the US and comparable regulatory
      offices in Europe. The most extensive experimental and clinical experience was
      gathered with the H.E.L.P. System by B. Braun Melsungen, which differs from other
      apheresis techniques by its efficiency to eliminate LDL, Lp(a), fibrinogen and
      CRP simultaneously. The clinical results obtained to date with the H.E.L.P.-LDL
      apheresis clearly demonstrate a significant reduction of risk factors and
      clinical events, as well as an excellent long-term tolerance. A comprehensive
      literature survey on H.E.L.P. is part of this communication.

PMID- 14663598
TI  - [Clinical long-term results of H.E.L.P.-apheresis].
AB  - The heparin-induced extracorporeal LDL-precipitation (H.E.L.P.) procedure was
      approved by the German Health Authorities with the requirement of performing a
      five year postmarketing surveillance (PMS) study to document safety and
      efficiency data. A postmarketing surveillance resembles a patient registry
      including a patient population inhomogeneous to a certain degree with respect to
      clinical diagnosis and stage of the disease, respectively. Compared to clinical
      studies a patient registry differs by the length of regular documentation due to
      the fact that new patients can be recruited at any time during the 5 years of
      registry documentation. These restrictions must be considered to correctly
      interpret the PMS data presented. During the study period, a total of 628
      patients were recruited at 82 HELP-treatment facilities. The mean pre-treatment
      LDL value was 276 mg/dl and the mean HDL value 45 mg/dl corresponding to an
      atherogenic index of 6.1. In addition to the regular HELP treatment, most of the
      patients were treated by diet and statins (88.5%) or other lipid-lowering drugs.
      Although 90% of all patients had been treated by maximal conventional lipid
      lowering drug treatment, 42.2% of all documented patients had LDL plasma values
      >250 mg/dl; 19% of all documented patients exerted LDL values of >400 mg/dl and
      were therefore classified as homozygous FH patients. The mean surveillance time
      was 2 years. For 243 patients documentation was stopped early due to varying
      reasons: 19 patients passed away during the postmarketing surveillance; in 7
      cases HELP treatment was discontinued because of adverse effects, and 78 patients
      changed the LDL apheresis treatment device and were therefore lost for the PMS.
      Lacking patient compliance and refusal of further reimbursement of the treatment
      costs were reasons in 28 patients, and medical reasons were documented for
      another 111 patients for early termination of apheresis treatment. From 58 991
      documented single HELP-treatment procedures, the treated plasma volume was
      available as a measure for treatment efficiency. The mean treated plasma volume
      was 2.8 l; in 83.9% of all documented treatments a minimum of >2.5 l was treated.
      The mean treatment interval was 9.9 days. Out of 628 patients, 158 complained of
      angina before regular HELP treatment. At the final examination, the majority of
      these patients (87%) reported marked improvement, similar to self-reported
      improvement of dyspnea on exertion. The incidence of cardiac events including
      death, myocardial infarction, angioplasty and CABG was lower in patients with LDL
      >250 mg/dl (12.3%) as compared to patients with LDL <250 mg/dl (17%). For all
      patients, the relative rate of events was 16%. One further aim of the PMS study
      was the documentation of adverse effects of regular HELP treatment using a
      questionnaire. During five years of PMS, 2734 (4.6%) adverse effects during 59
      121 documented single HELP treatments in 622 patients were recorded. To define
      adverse effects directly related to the HELP procedure, adverse effects of the
      concomitant drugs administered require careful consideration. Therefore, the
      incidence of adverse effects directly attributable to HELP does not exceed 1-2%.

PMID- 14663599
TI  - [Myocardial perfusion under H.E.L.P. -apheresis. Objectification by PET].
AB  - Due to endothelial dysfunction (ED), coronary vasodilation capacity is reduced in
      patients with hypercholesterolemia. Cholesterol lowering may largely restore
      endothelial function. Currently, it is supposed that the onset of this
      therapeutic effect takes weeks or even months. However, by means of LDL
      apheresis, a significant LDL reduction may be achieved within hours. Dynamic
      quantitative positron emission tomography (PET) performed before and after LDL
      apheresis showed that mean global myocardial perfusion can be measured at rest
      and after pharmacological vasodilation with dipyridamole using N13 ammonia as
      tracer.A total of 35 patients (11 women and 24 men) with documented coronary
      heart disease and hypercholesterolemia underwent PET immediately prior to LDL
      apheresis and 18-20 hours thereafter. In addition to the decrease in LDL
      cholesterol (from 175+/-50 to 77+/-25 mg/dl) and fibrinogen (from 287+/-75 to
      155+/-52 mg/dl), a significant improvement of myocardial blood flow under
      dipyridamole (177+/-59 vs 217+/-82 ml/min 100 g, p<0.0001), of coronary flow
      reserve (2.10+/-0.82 vs 2.62+/-1.02, p<0.0001) and of minimal coronary resistance
      (0.56+/-0.20 vs 0.44+/-0.17 mmHg 100 g min/ml, p<0.0001) were achieved. Plasma
      viscosity decreased only by 7.8%. Within 20 hours after single LDL apheresis a
      20% improvement of coronary vasodilation capacity was noninvasively demonstrated
      and quantified.

PMID- 14663600
TI  - [H.E.L.P. apheresis and oxidative stress].
AB  - LDL apheresis according to the H.E.L.P. procedure is used to treat severe
      hypercholesterolemia in patients with coronary artery disease (CAD). It has been
      argued that either hypercholesterolemia or extracorporeal treatment may enhance
      oxidative stress. The balance between antiand pro-oxidative agents during
      H.E.L.P. apheresis was investigated by several groups. An increased resistance of
      LDL to oxidative modification after H.E.L.P. treatment is the leading result of
      these investigations.We studied the influence of a single H.E.L.P. apheresis on
      plasma concentrations of lipid peroxidation parameters in patients with
      heterozygous familiar hypercholesterolemia and advanced CAD enrolled in a chronic
      apheresis program once a week. Single H.E.L.P. apheresis reduced plasma
      concentrations of oxidized LDL and malondialdehyde without having an influence on
      cellular Cu/Zn superoxide dismutase (Cu/ZnSOD). The antioxidative serum capacity
      declined to some degree after apheresis whereas plasma concentration of 8
      isoprostan- PGF2 alpha increased.In H.E.L.P. apheresis, the antioxidative effects
      prevail. Oxidation of lipids and severe modification of enzymatic and non
      enzymatic antioxidants during extracorporeal circulation do not counterbalance
      the benefit of LDL reduction.

PMID- 14663602
TI  - [The role of intravascular ultrasound examination for assessment of graft
      vasculopathy].
AB  - Long-run development of heart transplanted patients is predominantly determined
      by the occurrence of graft vasculopathy. Due to the commonly diffuse and
      concentrical appearance of plaque in the coronary vessels, the disease defies, at
      least in the early stage, the conventionally used angiographic diagnostic
      procedures with radiocontrast agents. With the possibility to differentiate not
      only the lumen but also structures of the vessel walls and different tissue
      types, intracoronary ultrasound (IVUS) of coronary vessels yields entirely new
      insights in the development, the course and the prognostic importance of graft
      vasculopathy. Besides the extended scientific application in order to investigate
      the pathophysiology of graft vasculopathy and the assessment of therapeutic
      strategies, regular follow-ups with IVUS are nowadays used in many centers in
      routine care after heart transplant.

PMID- 14663601
TI  - [Prevention of early graft occlusion after coronary bypass grafting by post
      operative reduction of plasma fibrinogen by H.E.L.P. apheresis. First evaluation
      of 12 patients treated during our study (44 bypasses)].
AB  - BACKGROUND: Early graft occlusion is a known complication after CABG (Coronary
      Artery Bypass Grafting). The thromboembolic closure of the bypass occurs at a
      frequency of 5-15%, depending on the implemented vessel (arterial or venous
      graft). Fibrinogen as a substrate of thrombus formation plays a major role in
      both primary and secondary haemostasis. The operative trauma triggers the acute
      phase-response and also activates the clotting process. This leads to high
      fibrinogen levels of up to 600 mg/dl postoperatively, providing an impaired
      haemorrheological pattern which promotes thrombus formation. In a prospective
      pilot-study we examined whether drastic postoperative lowering of fibrinogen by
      H.E.L.P.-(Heparin-mediated Extracorporeal LDL-/Fibrinogen Precipitation)
      apheresis can prevent early graft vessel closure in patients undergoing CABG.
      METHODS: For the purpose of this study 12 male patients (mean age 60+/-5.8 years)
      who underwent multivessel CABG were recruited between 12/2000 and 2/2002
      according to a GCP approved protocol. The postoperative fibrinogen levels of the
      patients were monitored and H.E.L.P. apheresis was applied when plasma fibrinogen
      levels exceeded >350 mg/dl on day 1 and >250 mg/dl every following day up to day
      8 after the operation. Pre- and post apheresis blood samples were obtained and
      reduction of plasma fibrinogen, LDL-Cholesterol and CRP were determined. Coronary
      angiography was performed within the 9th-16th postoperative day. To investigate
      the long term outcome a second coronary angiography was performed half a year
      after the operation. RESULTS: A total of 44 bypass grafts (23 arterial; 21 vein
      grafts) were implemented in 12 patients (mean 3.6/patient) and a total of 66
      H.E.L.P.-Apherses from day 1-8 were postoperatively applied (mean 5.5/patient).
      Fibrinogen levels were lowered from a maximum on day 2 of 447+/-112.2 mg/dl (pre
      apheresis) to a minimum on day 8 of 228+/-46.2 mg/dl (pre-apheresis)
      demonstrating a reduction of 50%. Per single treatment the fibrinogen was lowered
      from 357+/-93 mg/dl (pre-apheresis) to 157+/-46 mg/dl (post apheresis);
      reduction: 55%. Coronary angiography revealed graft patency in 43 of 44 grafts
      (97.7% patency). The one occluded bypass was an Y-graft to a diagonal branch less
      than 1mm in diameter. No bleeding or H.E.L.P. related complications were
      observed.Up to now 7 of 12 patients underwent the second coronary angiography
      according to the study protocol. Apart from the already immediately
      postoperatively occluded Y-graft no new bypass-occlusion was revealed.
      CONCLUSIONS: Early and extensive reduction of postoperatively elevated plasma
      fibrinogen levels by H.E.L.P. apheresis seems to be an efficient and safe
      therapeutic approach for preventing early graft occlusion in patients undergoing
      multivessel CABG.

PMID- 14663603
TI  - [Lipoprotein(a): Aspects of pathophysiology, epidemiology and treatment].
AB  - Lipoprotein(a) is an LDL-like particle disulfide-linked to apo(a). Plasma Lp(a)
      concentrations are mostly determined genetically. Apo(a) size polymorphism is
      inversely related to plasma Lp(a). Numerous studies had found Lp(a) or the apo(a)
      polymorphism to have atherogenic and thrombogenic potential. There are some
      prospective trials which described significantly higher Lp(a)-levels in middle
      aged populations with cardiovascular events. Some studies found contrasting
      results; however, most of them have not been well designed or show methodological
      problems. Progress regarding effective therapeutic interventions has been slow
      and inadequate. This and lack of laboratory standardization explain why there are
      still hardly any interventional studies. In particularly severe cases,
      extracorporeal Lp(a) removal may be the only effective treatment option. Due the
      lack of prospective studies, this treatment option is not widely accepted in
      Germany yet.

PMID- 14663604
TI  - [Treatment of sudden hearing loss through Fibrinogen/LDL-apheresis. A
      prospective, randomized multicenter trial].
AB  - INTRODUCTION: Sudden sensorineural hearing loss (SSHL) is thought to be of
      various origins. Disturbances of microcirculation, autoimmune pathology and viral
      infection are among the most likely causes. Acute reduction of plasma fibrinogen
      and serum LDL positively influences hemorheology and endothelial function and
      might thus be an effective therapy for SSHL. OBJECTIVE: To test the hypothesis
      that fibrinogen/LDL-apheresis is as effective or superior to conventional therapy
      with plasma expanders and prednisolone in the treatment of SSHL. DESIGN:
      controlled, prospective, randomized, multicenter trial. SETTING AND PATIENTS: 201
      patients were recruited from 01/2000 to 6/2001 at the University Clinics of
      Munich, Berlin, Hamburg and Bochum. Inclusion criteria was sudden sensorineural
      hearing loss of unknown origin within 6 days of onset. INTERVENTIONS: Single
      fibrinogen/ LDL-apheresis infusion of prednisolone (250 mg, tapered by 25 mg
      daily), hydroxyethyl starch (500 ml, 6%) and pentoxifylin (400 mg/day). MAIN
      OUTCOMES: Improvement of pure tone thresholds 48 h after onset of therapy.
      RESULTS: Over all improvement of pure tone thresholds in the fibrinogen/ LDL
      apheresis treated patients is slightly but not significantly better than in the
      standard therapy group. After 48 h, 50% speech perception in the fibrinogen/ LDL
      apheresis group (21.6+/-20.1 dB) is significantly (p<0.034) better than in the
      standard group (29.3+/-29.4 dB). Patients with plasma fibrinogen levels of more
      than 295 mg/dl have a substantial and significantly (p<0.005) better improvement
      of speech perception (15.3+/-17.3 dB) than standard treated patients (6.1+/-10.4
      dB). CONCLUSIONS: Fibrinogen/LDLapheresis is at least equally effective compared
      to prednisolone treatment in sudden hearing loss. Selected patients with plasma
      fibrinogen of more than 295 mg/dl improve significantly better when treated with
      fibrinogen/LDLapheresis.

PMID- 14663605
TI  - [LDL-Apheresis for the treatment of hyperchylomicronemia-induced pancreatitis].
AB  - Severe hyperchylomicronemia due to defects of lipoprotein lipase or apoC-II is a
      rare cause for acute pancreatitis. Food with a high content of fat, as well as
      alcoholic or hormonal influences, can lead to excessive hypertriglyceridemia.
      Especially hyperchylomicronemia due to hormonal influences during pregnancy are
      troublesome. Here, we are confronted with both the risk to the mother as well as
      the vital risk to the unborn. Conventional plasma apheresis has been used to
      successfully eliminate chylomicrons and, thus, the primary cause of chylomicron
      induced pancreatitis. Most recently, we reported the use of selective LDL
      apheresis in a 24-year-old pregnant woman (thirteenth week of pregnancy), who was
      admitted with the signs of acute pancreatitis to our hospital. The patient was
      known to have a history of severe hyperchylomicronemia and she had also been
      treated several years before for acute pancreatitis by LDL-apheresis. Her
      triglycerides were severely elevated (11500 mg/dl) and, in order to achieve a
      rapid decrease of chylomicrons, we decided to treat her by selective LDL
      apheresis utilizing HELP-apheresis. The treatment was well tolerated and within
      half an hour the patient was free of any abdominal pain. However, due to the
      enormous triglyceride load, we needed to change the precipitate filters several
      times and at the end of the treatment triglyceride levels were 6600 mg/dl. Under
      a low-fat diet (<30 gram fat per day), the follow-up was uneventful and the
      patient delivered a healthy baby at the end of week 39. We conclude that LDL
      apheresis is a safe and rapid procedure to eliminate chylomicrons in chylomicron
      induced pancreatitis.

PMID- 14663606
TI  - [QUASA-the apheresis registry].
AB  - Quality saving measures are required at the execution of extracorporeal LDL
      apheresis therapy (LDL apheresis) by the NUB guidelines of the national committee
      of physicians and health insurance. The saving measures apply to specialist,
      organizational and apparatical conditions for execution and accounting of
      treatment methods. Furthermore, as a result of the lawful requirements of SGB V,
      complementary BUB guidelines were introduced in 1999. These ought to engage the
      therapeutic benefit of a LDL apheresis treatment. Beyond measures for quality
      assurance at execution a documentation of treatment is explicitly demanded. For
      two years now the non-profit Quasa gGmbH has been developed the quality assurance
      registry for LDL apheresis with the background of those requirements. Since March
      2003 the apheresis physicians can voluntarily take part in the registry
      initiative by internet. Beside the clinical patient's medical history, treatment
      relevant data are recorded. Because of the analysis of the nationally ascertained
      clinical data, for the first time it will be possible for the medical profession
      to fulfill the guidelines of quality assurance for LDL apheresis. Moreover the
      treating apheresis physicians can establish an EDV-based individual patient
      documentation. All necessary measures of data protection and data security are in
      process on the technical and logistic realization of this registry initiative. An
      epidemiological data evaluation is regularly accomplished and the results are
      provided to the public.

PMID- 14663607
TI  - [Why is obstructive sleep apnea (OSA) a cardiovascular risk factor?].
AB  - Patients with obstructive sleep apnea (OSA) frequently suffer from cardiovascular
      diseases. Mechanisms like intrathoracic pressure variations, changes in blood
      gases (hypoxia), arousals and neurohumeral adaptation mechanisms, combined with
      breathing disorders are causing these cardiovascular sequelae. In particular
      repetitive hypoxemia and activation of the sympathetic nervous system have to be
      considered as stressors for the cardiovascular system. Special clinical findings
      should take OSA into consideration as a differential diagnosis. A systematic
      anamnesis with questions to daytime conditions (hypersomnia, decrease of
      performance), snoring and apneas while sleeping is easy to ascertain, and will
      lead to the correct diagnosis in more than 90% of cases. The extent and need for
      therapy should be assessed by three criteria: 1) daytime symptoms, 2) the extent
      of breathing disorder and 3) cardiovascular comorbidity.

PMID- 14663608
TI  - Effects of education, self-care instruction and physical exercise on patients
      with chronic heart failure.
AB  - BACKGROUND: Evidence is now evolving of the importance of team management for
      patients with chronic heart failure. This includes education, patient self-care
      and physical exercise training. How such programs should be implemented is still
      under discussion. AIM: To assess the efficacy of an in-hospital rehabilitation
      clinic-based program, we studied its influence on cardiopulmonary parameters and
      quality of life in an outpatient setting. METHODS AND RESULTS: 75 patients (62
      male, 13 female, mean age 65+/-8 years) underwent an exercise program including
      education, bicycle ergometer, muscle strength training and the 6-min walk test as
      a training unit for 4 weeks. Patients were studied at baseline (T1), before
      discharge (T2) and after a follow-up period of 29.9+/-5.5 weeks (T3). Baseline
      data (T1): left ventricular ejection fraction (LVEF): 33.8+/-7.6%, left
      ventricular end-diastolic volume (LVEDV): 130+/-51 ml, peak VO(2): 12.3+/-4.3
      ml/kg, maximum work load (Watt max): 71+/-27 W. At discharge (T2) and follow-up
      (T3) LVEF increased to 36.8+/-8% and 41.8+/-9.2%, LVEDV decreased to 127+/-43 ml
      and 114+/-40 ml, peak VO(2) increased to 14.1+/-5.1 ml/kg and 15.2+/-5 ml/kg, and
      Watt max increased to 84+/-28 Wand 98+/-42 W (all p<0.01). Quality of life
      improved significantly at discharge and follow-up in nearly all domains and in
      the summary score for physical health. There were no significant changes for
      anxiety and depression at T2 and T3. CONCLUSION: A specialized in hospital
      rehabilitation program including education, patient self management and training
      has a sustained positive effect on cardiopulmonary parameters and physical well
      being.

PMID- 14663609
TI  - [Analysis of inter- and intraventricular asynchrony by tissue Doppler
      echocardiography].
AB  - BACKGROUND AND INTRODUCTION: Cardiac resynchronization therapy (CRT) is a
      promising non-pharmacological treatment option for patients (pts) with severe
      severe heart failure (CHF), systolic left ventricular (LV) dysfunction, and
      ventricular conduction abnormalities (VCA). Pt selection for CRT, however, is
      still controversial. Tissue Doppler echocardiography (TDE) can be used to analyze
      regional wall motion with high temporal resolution. PATIENTS AND METHODS: In 33
      CHF pts with VCA (QRS width > or =140 ms) and 20 normal probands, left and right
      ventricular (RV) filling and emptying were analyzed by flow and tissue Doppler to
      assess regional (anterior, lateral, inferior, and septal) asynchrony within the
      LV as well as asynchrony between the RVand LV. All time measurements were
      corrected for a heart rate of 60 bpm. Results Maximum interventricular and
      segmental intraventricular delay was 30 ms in the normals. LV asynchrony, defined
      as a regional delay of > or =40 ms, was found in 29/33 (88%) of the CHF pts, in 4
      cases there was synchronous LV contraction despite VCA. In the pts with LV
      asynchrony, 22 (67%) showed the maximum delay in the lateral wall, 7 (21%) in the
      septum. Inter- and intra-ventricular asynchrony correlated weakly. CONCLUSIONS:
      In many CHF pts with VCA, there is a delay both between the two ventricles, and
      among different LV regions. Predominantly but not exclusively, the LV lateral
      wall shows the maximum intra-LV delay. Some CHF pts, however, seem to have a
      synchronous LV contraction despite VCA. TDE thus adds important information for
      pt selection with respect to CRT.

PMID- 14663610
TI  - Mid-systolic septal deceleration. A new sign of left ventricular outflow tract
      obstruction obtained by color-coded tissue Doppler echocardiography.
AB  - Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by the presence
      of a dynamic left ventricular outflow tract gradient. We studied septal
      longitudinal motion by color coded tissue Doppler echocardiography in a 69-year
      old HOCM patient during and after catheter based treatment by trans coronary
      alcohol ablation of septal hypertrophy. The presence of dynamic left ventricular
      outflow tract obstruction was associated with a characteristic abrupt mid
      systolic septal deceleration pattern in the tissue Doppler velocity trace. Five
      weeks after treatment, this pattern was no longer visible at rest.

PMID- 14663611
TI  - [Intraoperative cooled-tip radiofrequency ablation in patients with atrial
      fibrillation undergoing open heart surgery].
AB  - METHODS: A total of 113 patients with chronic permanent (104) or paroxysmal (9)
      atrial fibrillation underwent open heart surgery plus an additional
      antiarrhythmic procedure using saline-irrigated cooled-tip radiofrequency
      ablation (SICTRA) for biatrial or left atrial linear lesions. Ablation was
      performed with steps of short (5 seconds) ablation around the pulmonary vein
      ostia and interconnecting lines. Postoperative complications and conversions to
      sinus rhythm were followed up (mean follow-up duration 17+/-14 months). RESULTS:
      Of the 113 patients, 16 died during follow-up (day 3 up to 33 months) resulting
      in a cumulative survival of 79% (2 sudden cardiac deaths, 2 gastrointestinal
      bleedings, 1 renal bleeding, 2 mediastinitis, 1 endocarditis, 1 hemorrhagic
      insult, 2 respiratory insufficiencies and 2 unknown). Three patients died between
      day 3 and 6 (30-day mortality 3%) due to low cardiac output. Complications
      occurred in 19% of the patients including 4% bleeding, 1% pneumothorax, 3%
      sternal dehiscence, 3% reversible low cardiac output, 6% reversible respiratory
      insufficiency, 2% TIAs and 1% intra aortal balloon pump implantation. Conversion
      to sinus rhythm usually occurred spontaneously within 6 months resulting in a
      cumulative percentage of 80% in sinus rhythm. In these patients, 85% showed
      biatrial contraction. CONCLUSIONS: SICTRA to treat atrial fibrillation can safely
      and effectively be combined with different surgical procedures. Mortality and
      complication rates are comparable to cardiac surgery without antiarrhythmic
      procedures. No severe procedure-related complications were noted when a stepwise
      ablation approach during open heart surgery was used. Antiarrhythmic surgical
      procedures are highly effective in restoring sinus rhythm in patients with atrial
      fibrillation. Is a modified approach using intraoperatively cooled-tip
      radiofrequency ablation to induce linear lesions safe and effective in the
      treatment of atrial fibrillation in cardiosurgical patients?

PMID- 14663612
TI  - Comparison of different cardiac markers in monitoring percutaneous coronary
      interventions with frequent use of stents and gpIIbIIIa-antagonists.
AB  - Studies from the early 1990s found elevations of creatine kinase (CK) and its
      isoform CK-MB in 5-30% of patients after PCI, indicating minor myocardial damage.
      Less is known about the influence of modern improved PCI-techniques on the
      frequency of elevated cardiac markers and the correlation between different
      commonly used markers, especially cardiac troponins. From 1997 to 2001, 1486
      patients undergoing PCI during the regular working hours were included in the
      prospective "Ludwigshafen Infarctlet Registry". Myocardial infarction in the past
      48 hours was an exclusion criterion. Clinical and procedural data were
      documented. Follow-up data were obtained from discharge up to one year. PCI
      related elevations of troponin T were found in 18%, of total-CK in 11%, of CK-MB
      in 33% and of myoglobin in 23% of cases. The correlation between the different
      markers was poor. Compared with troponin T, other markers showed low sensitivity
      (total-CK 58%, CK-MB 27%, myoglobin 22%) and, especially total-CK, low
      specificity. Stenting, side branch occlusion or major dissection, complex lesion
      morphology, gpIIbIIIa-antagonist application, proximal stenosis and unstable
      angina were independent predictors of an elevated troponin T in multivariate
      analysis. Due to this weak correlation between more specific and sensitive
      troponins and the other markers, troponins are preferred in monitoring after PCI.
      In addition to lesion characteristics, particularly stenting is associated with
      an increased rate of elevated troponin.

PMID- 14663613
TI  - Atorvastatin stent coating does not reduce neointimal proliferation after
      coronary stenting.
AB  - PURPOSE: Statins seem to be suitable for restenosis prevention via reduction of
      smooth muscle cell proliferation, anti-inflammatory effects, and improvement of
      endothelial function. The aim of the present study was to test the efficacy of an
      atorvastatin stent coating for restenosis inhibition in the porcine coronary
      stent model. METHODS AND RESULTS: Twenty stents (BiodivYsio Matrix LO, uncoated
      or with 56 microg atorvastatin load) were implanted in LAD and CX coronary
      arteries of 10 domestic pigs with an over stretch ratio of 1.25. Quantitative
      angiography and histomorphometry of the stented arteries asserted statistic
      equality of the baseline parameters between the control and treatment group.
      After 28 days, there was no significant difference in parameters describing in
      stent restenosis (neointimal area 3.14 +/- 1.13 mm(2) [control] vs. 3.12 +/- 1.07
      mm(2) [atorvastatin stent]; p = 0.978). However, there was a trend towards a
      lower degree of inflammation in the atorvastatin stent group. CONCLUSION:
      Atorvastatin stent coating showed a trend towards reduced local inflammation near
      the stent struts, but could not reduce neointimal formation in the porcine
      coronary over stretch model.

PMID- 14663614
TI  - [Lyme carditis and symptomatic sinus node dysfunction].
AB  - Lyme carditis is typically associated with AV nodal conduction abnormalities. We
      describe the case of a 66 year old female patient, who experienced a series of
      syncopal attacks after several tick bites two weeks earlier. ECG monitoring
      revealed recurrent sinus arrest with a maximum pause duration of 8 seconds. After
      institution of antibiotic therapy for Lyme carditis, sinus node dysfunction
      resolved rapidly and the patient had no further syncopes. Pacemaker implantation
      was not necessary. We therefore have to assume that in this patient Lyme carditis
      was the cause of symptomatic sinus node dysfunction.

PMID- 14663615
TI  - [The arrhythmogenic right ventricular cardiomyopathy (ARVC)].
AB  - The following report illustrates the case of a 40-year old patient, who was
      transferred to our hospital because of a symptomatic sustained ventricular
      tachycardia (VT). The documented VT showed typical left bundle branch block
      morphology with an inferior axis, which was accompanied by repolarization
      abnormalities in the right precordial leads, as revealed by the surface ECG.
      While coronary angiography allowed the exclusion of an obstructive coronary heart
      disease and confirmed an intact left ventricular function, the right ventricular
      angiography as well as the MRI demonstrated not only reduced right ventricular
      function but also regional abnormalities of contraction in the inferior and
      diaphragmal regions and typical "outpouchings" and "bulgings". The MRI also
      provided evidence for sporadic fatty infiltrations of the right ventricle. In the
      electrophysiological study, sustained VT could be reproducibly induced, while
      showing the typical RVOT configuration, which corresponded to the clinically
      apparent VT. Since these examination results matched with the criteria of McKenna
      et al., arrhythmogenic right ventricular cardiomyopathy was diagnosed. The
      patient underwent implantation of a cardioverter-defibrillator (ICD) and medical
      treatment with metoprolol. This particular case report was selected because it
      shows a typical presentation of an ARVC. Furthermore, the present example offers
      the possibility of demonstrating that in the case of an ARVC in the regions of
      the right ventricle, arrhythmogenic areals can also be found which seem
      morphologically inconspicuous.

PMID- 14663616
TI  - [Isolated myocardial noncompaction in childhood-case report and review of the
      literature].
AB  - The diagnostic work-up for the first syncopal episode of a 14-year-old female
      adolescent revealed the morphology of an isolated myocardial non-compaction on
      echography. Angiography and biopsy of the left ventricle confirmed the diagnosis.
      Despite a reduced shortening fraction (FS 21%) and frequent premature atrial
      beats, there were no further cardiac or extracardiac symptoms. After
      establishment of therapy with beta-blockade, digitalis, angiotensin converting
      enzyme inhibition and acetylsalic acid, the follow-up over 24 months was good;
      the implantation of an automatic implantable cardioverter-defibrillator is
      planned.

PMID- 14663624
TI  - Evaluation of the effects of methylprednisolone pulse therapy in patients with
      systemic lupus erythematosus with brain involvement by Tc-99m HMPAO brain SPECT.
AB  - Methylprednisolone pulse therapy (MPT) was introduced to avoid life-threatening
      complications in patients with systemic lupus erythematosus (SLE) with brain
      manifestations; however, the efficacy of MPT in SLE patients with brain
      involvement is still uncertain and needs to be objectively evaluated. We enrolled
      15 female SLE patients with neuropsychiatric manifestations in this study. All
      patients had normal brain MRI and abnormal brain HMPAO-SPECT findings. Follow-up
      HMPAO-SPECT studies were conducted 2 weeks after MPT. Serum levels of
      anticardiolipin antibodies (ACA) and anti-ribosomal P antibodies (anti-P) were
      measured before and after MPT. Before MPT, 7 patients were positive for ACA and 7
      patients were positive for anti-P. After MPT, none of the 15 patients
      demonstrated positive serologic findings or neuropsychiatric manifestations.
      Based on the follow up brain HMPAO-SPECT images following MPT, 13 patients showed
      disappearance of the perfusion defects and 2 patients showed partial recovery of
      rCBF. Brain HMPAO-SPECT imaging is a logical and objective tool for measuring the
      effects of MPT in SLE patients with brain involvement by determining of changes
      in rCBF.

PMID- 14663625
TI  - Current trends in treatment of osteoid osteoma with an emphasis on radiofrequency
      ablation.
AB  - This article reviews current trends in the treatment of osteoid osteoma with an
      emphasis on the evolving use of radiofrequency thermoablation as a primary
      definitive treatment and for recurrent and residual lesions. In so doing, the
      article reviews merits and relative disadvantages of both surgical and non
      surgical imaging-guided techniques in treatment. Radiofrequency ablation of
      osteoid osteoma is a highly effective, efficient, minimally invasive and safe
      method of treating osteoid osteoma. Clinical success range from 76 to 100%.
      Surgery remains the standard treatment in cases where histology of the lesion is
      in doubt, neurovascular structures are within 1.5 cm or in repeated failure of
      any other minimally invasive ablative technique or percutaneous resection.
      Clinical success of surgery ranges from 88 to 100%. Laser interstitial thermal
      therapy shares many of the advantages and much of the success of radiofrequency
      thermoablation but has not been as available. Clinical success ranges from 87 to
      100%. Cryotherapy, ethanol therapy and imaging-guided excision remain second-line
      therapies. Clinical success ranges from 77 to 100% for imaging-guided resection
      and 100% for ethanol therapy.

PMID- 14663626
TI  - Coronary artery disease: new insights and their implications for radiology.
AB  - Coronary artery disease (CAD) diminishes local, regional, or global blood supply
      to the heart and is most commonly caused by coronary atherosclerosis. New
      insights into the etiology of atherosclerosis suggest that CAD is an inflammatory
      disorder that responds well to modulation rather than an unchangeable chronic
      process. Since 75% of all acute coronary syndromes result from rupture of
      atherosclerotic plaques, factors causing rupture have a crucial role. Magnetic
      resonance imaging and CT have the potential to visualize the composition of
      coronary artery plaques and thus to identify plaques at risk. Considering the new
      insights into stunning and hibernation, myocardial late enhancement on MRI might
      provide pivotal information for therapeutic decision making among lysis therapy,
      catheter intervention, and bypass surgery. Exercise electrocardiography without
      or with right precordial leads, stress echocardiography, and stress scintigraphy
      are simple clinical procedures to identify CAD with high sensitivities of 67, 92,
      76, and 88%, respectively. The MRI and CT have to be compared with these good
      results. Nevertheless, we are expecting that MRI and CT will replace the
      conventional diagnostic modalities, gain a central role in diagnosing patients
      with suspected CAD, and prove to be cost-effective in this regard.

PMID- 14663627
TI  - Induction of early light-inducible protein gene expression in Pisum sativum after
      exposure to low levels of UV-B irradiation and other environmental stresses.
AB  - Plants are constantly subjected to environmental changes and have developed
      various defence mechanisms to facilitate their continued existence. Pisum sativum
      plants were exposed to low levels of UV-B radiation and ELIP (early light
      inducible proteins) mRNA, with a probable protective function, was rapidly and
      strongly induced during this type of stress. To our knowledge, this is the only
      photosynthetic gene that is up-regulated following exposure to UV-B, and this
      result has to be compared with studies predominantly reporting down-regulation by
      UV-B of genes encoding proteins localised in the plastid. The expression pattern
      of ELIP mRNA in pea was also investigated during salt, wounding and ozone stress.
      The transcript levels of ELIP were induced after the salt and wounding treatments
      but not during ozone fumigation.

PMID- 14663628
TI  - Phenothiazines suppress proliferation and induce apoptosis in cultured leukemic
      cells without any influence on the viability of normal lymphocytes.
      Phenothiazines and leukemia.
AB  - PURPOSE: The purpose of the present study was to investigate the effects of
      phenothiazines (at clinically relevant doses) on the viability and proliferation
      of leukemic cell lines and normal lymphocytes, and to investigate the possibility
      of specific induction of apoptosis in leukemic cells. METHODS: Phenothiazines
      with different chemical structure and hydrophobicity were used: chlorpromazine
      (CPZ); levomepromazine (LVPZ); prometazine (PMZ); trifluoperazine (TFPZ);
      thioridazine (TRDZ). The leukemic cell lines used were: Daudi and Raji (derived
      from Burkitt's lymphoma), K-562 (derived from myelogenous leukemia), and BALL-1,
      MOLT-4, HPB-ALL and CCRF-HSB-2 (derived from acute lymphoblastic leukemia). The
      cytotoxicity of the phenothiazines was determined by a CellTiter-Glo luminescent
      cell viability assay, using ATP bioluminescence as a marker of cell viability as
      well as a marker of mitochondrial activity. The proliferation of leukemic cells
      was determined using a CellTiter-AQ cell proliferation assay which is based on
      the reduction of a methyl-tetrazolium compound to the formazan product. Apoptosis
      induction was estimated using phosphatidylserine (PSer) translocation to the cell
      surface and DNA fragmentation as characteristics of the process. RESULTS:
      Phenothiazines (at concentrations in the range 0.1-10 micro M) did not affect the
      viability of normal lymphocytes during a 24-h incubation. Moreover, about 15-20%
      increase in ATP bioluminescence was observed in normal cells during treatment
      with 40 micro M phenothiazines. In contrast, the phenothiazines manifested strong
      cytotoxicity and antiproliferative activity against leukemic cells. The most
      powerful drugs were TFPZ and TRDZ, followed by CPZ. They showed a significant
      cytotoxic effect against leukemic cells even at 5-10 micro M. The most sensitive
      cell lines were MOLT-4 and Raji, and the most resistant were HPB-ALL and CCRF-HSB
      2. All phenothiazines induced PSer exposure on the surface of leukemic cells, but
      not of normal lymphocytes. TFPZ, TRDZ and CPZ also induced DNA fragmentation in
      almost all leukemic cell lines during a 48-h incubation. The strongest apoptotic
      agent was TRDZ. The apoptosis induction was not accompanied by a significant
      release of cytochrome c from the mitochondria into the cytoplasm of native cells.
      Moreover, the drugs markedly suppressed Ca(2+)-induced cytochrome c release in
      isolated mitochondria of leukemic cells. CONCLUSIONS: The results suggest that in
      clinically relevant doses (up to 20 micro M) some phenothiazines (TFPZ, TRDZ,
      CPZ) expressed a selective cytotoxicity and antiproliferative activity, and
      induced apoptosis in leukemic cells without any influence on the viability of
      normal lymphocytes. It is considered that the mechanism of apoptosis induction in
      phenothiazine-treated leukemic cells is associated with inhibition of
      mitochondrial DNA polymerase and decreased ATP production, which are crucial
      events for the viability of cancer cells.

PMID- 14663629
TI  - Gene replacement method for determining conditions in which Bacillus subtilis
      genes are essential or dispensable for cell viability.
AB  - We describe a method for determining conditions in which Bacillus subtilis genes
      are essential or dispensable for cell viability. This method utilizes a
      chloramphenicol-resistant plasmid containing a temperature-sensitive (ts)
      replication origin. In this method, the target gene is first cloned into the ts
      vector and the recombinant plasmid is used to transform wild-type B. subtilis.
      The second step involves transformation of the resulting strain with a linear DNA
      fragment containing a second antibiotic resistance marker (tet) that disrupts the
      gene of interest. Selection for tetracycline resistance forces a double crossover
      between the chromosomal and fragment-borne copies of the gene, thereby replacing
      the wild-type gene in the chromosome with the disrupted allele. Cells survive
      even if the gene is essential by virtue of the complementing plasmid.
      Transformants are then grown at the non-permissive temperature for plasmid
      replication under various growth conditions. Isolation of chloramphenicol
      sensitive colonies indicates that the gene is dispensable, whereas the inability
      to isolate chloramphenicol-sensitive colonies indicates that the gene is
      essential. The general utility of this method is demonstrated by allowing
      disruption of mtrA and trpE under conditions that render each gene non-essential,
      but not under growth conditions in which each gene is essential.

PMID- 14663630
TI  - Preparation and investigation of 99m technetium-labeled low-density lipoproteins
      in rabbits with experimentally induced hypercholesterolemia.
AB  - Low-density lipoproteins (LDL) were radiolabeled in atherosclerosis studies. The
      aim was to investigate the biodistribution and uptake of 99mTc-labeled LDL by
      atherosclerotic plaques in experimentally induced hyperlipidemia. Rabbits were
      fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and
      atheromatous aortic plaques. A combination of preparative and analytical
      ultracentrifugation was used to investigate human LDL aliquots, to prepare
      radioactive-labeled lipoproteins and in rabbits with induced hyperlipidemia.
      Preparative density gradient centrifugation was applied for the simultaneous
      isolation of the major lipoprotein density classes, which form discrete bands of
      lipoproteins in the preparative tubes. The cholesterol and protein levels in the
      lipoprotein fractions were determined. LDL was subsequently dialysed against
      physiological solution and sterilized and apolipoprotein fragments and aggregates
      were eliminated by passage through a 0.22-micron filter. LDL was radiolabeled
      with 99mTc by using sodium dithionite as a reducing agent. Radiochemical purity
      and in vitro stability were controlled by paper chromatography in acetone. The
      labelling efficiency was 85-90% for human LDL. Two months after the start of
      cholesterol feeding, the total cholesterol in the blood serum had increased
      approximately 33-fold in comparison with the basal cholesterol content of
      hypercholesterolemic rabbits. Investigation of LDL was performed by Schlieren
      analysis after adjustment of the density of serum and underlayering by salt
      solution in a spinning ultracentrifugation capillary band-forming cell.
      Quantitative results were obtained by measuring the Schlieren areas between the
      sample curves and the reference baseline curve by means of computerized numerical
      and graphic techniques. In this manner we measured the concentrations of human
      LDL and analyzed rabbit LDL levels in induced hyperlipidemia. Gamma scintillation
      camera scanning of the rabbits was performed. Overnight fasted rabbits were
      injected in the marginal ear vein with 99mTc-labeled human LDL (4-10 mCi, 0.5-1.5
      mg protein). The initial scintigram showing a typical blood-pool scan, gradually
      changing with time to an image of specific organ uptake of radioactivity by the
      liver, kidneys and brain and in the bladder. Gamma camera in vivo scintigraphy on
      rabbits revealed visible signals corresponding to atherosclerotic plaques in the
      aorta and carotid arteries. Our results show that 99mTc-LDL can be used to assess
      the organ distribution pattern of LDL in the rabbit, and to detect and localize
      areas of arterial atherosclerotic lesions.

PMID- 14663632
TI  - Radiographic parameters of the hip joint from birth to adolescence.
AB  - BACKGROUND: Various qualitative and quantitative radiological geometrical
      parameters can be of great help when assessing dysplasia of the hip joint and in
      understanding developmental processes of the infant hip. There are few data on
      the normal values of the hip joint at different ages. OBJECTIVE: To perform
      radiographic measurements on hip joints considered to be anatomically normal and
      to provide data for each age group, thus describing features of the radiographic
      development of the hip. MATERIALS AND METHODS: Radiographs were examined from 355
      children (age 0-16 years) undergoing examination for scoliosis (long film),
      urography or plain abdominal radiography. Qualitative and quantitative signs were
      observed and measured, focusing on the Hilgenreiner, Wiberg and Idelberger angles
      and the decentric distance. RESULTS: Before the age of 9 years measurable data
      from neighbouring age groups differed significantly, indicating typical
      radiological changes of the joint. For the same age range, qualitative changes
      could also be observed. After 9 years of age, radiological development of the
      normal hip joint during childhood is much slower.

PMID- 14663631
TI  - The effect of diffusion, depolymerization and nucleation promoting factors on
      actin gel growth.
AB  - In eukaryotic cells, localized actin polymerization is able to deform the plasma
      membrane and push the cell forward. Depolymerization of actin filaments and
      diffusion of actin monomers ensure the availability of monomers at sites of
      polymerization, and therefore these processes must play an active role in
      cellular actin dynamics. Here we reveal experimental evidence that actin gel
      growth can be limited by monomer diffusion, consistent with theoretical
      predictions. We study actin gels formed on beads coated with ActA (and ActA
      fragments), the bacterial factor responsible for actin-based movement of Listeria
      monocytogenes. We observe a saturation of gel thickness with increasing bead
      radius, the signature of diffusion control. Data analysis using an elastic model
      of actin gel growth gives an estimate of 2x10(-8) cm(-2) s(-1) for the diffusion
      coefficient of actin monomers through the gel, ten times less than in buffer, and
      in agreement with literature values in bulk cytoskeleton, providing corroboration
      of our model. The depolymerization rate of actin filaments and the elastic
      modulus of the gel are also evaluated. Furthermore, we qualitatively examine the
      different actin gels produced when ActA fragments interact with either VASP or
      the Arp2/3 complex.

PMID- 14663633
TI  - The effect of ions at the surface of calcium oxalate monohydrate crystals on cell
      crystal interactions.
AB  - Magnesium is an abundant ion in biologic systems, including renal tubular fluid;
      however, the precise role of magnesium during the interaction of calcium oxalate
      crystals with cells has not been previously defined. In addition, the respective
      roles of calcium and hydrogen ions during the cell-crystal bonding interaction
      remain poorly defined. Here we report an atomic level three-dimensional study of
      a single crystal of calcium oxalate monohydrate (COM; whewellite) which was
      bathed in a solution of magnesium hexahydrate for 1 year. Magnesium was not
      incorporated into the structure of whewellite to any significant degree. Instead,
      COM accepted magnesium primarily as an adsorbate in a binding configuration
      which, as a surface phenomenon, is controlled by localized charge effects. The
      effect of magnesium and calcium on the efficiency of calcium oxalate crystal
      binding to renal cells was also investigated. When present in supraphysiologic
      concentrations (greater than 0.1 M), magnesium progressively inhibited adhesion
      of pre-formed COM crystals to cultured renal cells. Therefore, even though
      magnesium does not incorporate into the crystal structure of calcium oxalate,
      magnesium can exert important surface effects and change the interaction of pre
      formed COM with molecules anchored on the cell surface. Similarly, binding was
      nearly blocked when the exogenous calcium concentration was > or =0.1 M
      (supraphysiologic range), although in lower concentrations (within the
      physiologic range) exogenous calcium promoted crystal adhesion. Finally, the
      ambient hydrogen ion concentration also influenced calcium oxalate crystal
      interactions with renal cells, with maximal binding occurring at a pH of 4.
      Therefore, hypercalciuria and/or an acidic urine could each promote renal stone
      formation via increased crystal adhesion to renal cells, a previously under
      appreciated potential mechanism.

PMID- 14663634
TI  - Salvage treatment with docetaxel for recurrent epithelial ovarian cancer.
AB  - BACKGROUND: We investigated the clinical usefulness and toxicity of salvage
      treatment with docetaxel (70 mg/m2) infused at 3-week intervals in patients with
      recurrent ovarian cancer. METHODS: Retrospectively, we reviewed the clinical
      records of 24 patients diagnosed with recurrent ovarian cancer who had received
      the salvage treatment. RESULTS: A total of 128 courses (median, 5.5 courses;
      range, 2-8 courses) were administered to the 24 patients. The mean number of
      prior chemotherapy courses in the patients was 16.4 (range, 4-35 courses); they
      had already been treated heavily. The tumor response was evaluable at the end of
      the treatment in 20 patients, with the overall response rate being 15.0%. Using
      the criterion of serum carbohydrate antigen (CA)125 level, the response rate was
      13.0%. By the time of the final docetaxel treatment, all 24 patients had relapsed
      and 19 had died of the disease. The median progression-free interval was 4.6
      months (range, 1.3-7.8 months), and the median overall survival time was 13.7
      months (range, 2.1-27.0 months). While hematological toxicity was not severe,
      20.8% of patients experienced grade 3 asthenia/fatigue, and 5 patients refused
      further treatments with docetaxel because of this toxicity. CONCLUSIONS: Salvage
      treatment using docetaxel (70 mg/m2) was somewhat effective for recurrent ovarian
      cancer, although severe asthenia/fatigue was frequently observed. Docetaxel
      provides sufficient palliation of disease-related symptoms and some improvement
      in the length of life in patients with recurrent ovarian cancer, when
      asthenia/fatigue is mild.

PMID- 14663635
TI  - Weekly docetaxel for patients with platinum/paclitaxel/irinotecan-resistant
      relapsed ovarian cancer: a phase I study.
AB  - BACKGROUND: This study was designed to investigate the dose-limiting toxicity
      (DLT), maximum tolerated dose (MTD), and recommended dose (RD) of weekly
      docetaxel treatment in patients with relapsed ovarian cancer after the
      administration of platinum/paclitaxel/irinotecan. METHODS: Patients were enrolled
      on the basis of inclusion and exclusion criteria. Docetaxel was administered
      intravenously over a 60-min period on days 1, 8, and 15. Four dosage levels, 30,
      35, 40, and 45 mg/m2, were employed, and the dosage was escalated from level 1 to
      level 4. DLT criteria were established, and the DLT was used as the criterion for
      deciding the MTD and RD. RESULTS: Twelve patients were enrolled. No grade 3/4
      hematological toxicities were manifested at any dosage level. Grade 3/4
      nonhematologic toxicities were manifested at level 4, consisting of
      fatigue/asthenia in 2 patients and neuropathy/sensory toxicity in 1 patient.
      Level 4 (45 mg/m2) was thus judged to be the MTD, and the RD was concluded to be
      one level lower, i.e., level 3 (40 mg/m2). CONCLUSIONS: It was concluded that the
      RD for weekly docetaxel therapy is 40 mg/m2 per week in patients with relapsed
      ovarian cancer after the administration of platinum/paclitaxel/irinotecan.

PMID- 14663636
TI  - Induction of apoptosis by p53, bax, bcl-2, and p21 expressed in colorectal
      cancer.
AB  - BACKGROUND: We investigated the influence of genes on the apoptosis of colorectal
      tumor cells, based on DNA and mRNA kinetics. METHODS: In 30 colorectal cancer
      patients, we examined the mRNA expression of p53, bax, bcl-2, and p21(WAF1), and
      we also investigated the development of tumor cell apoptosis, using a terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL)
      method. RESULTS: TUNEL-positive cells showed a positive correlation with bax (P =
      0.010) and a negative correlation with p21 (P = 0.04). We also investigated the
      relationship between p53 point mutation, p21 immunostaining degree, and
      apoptosis, based on DNA ladder expression. A remarkable correlation (P = 0.0090)
      was found between p21 and apoptosis. CONCLUSIONS: The present study findings
      suggest that tumor cell apoptosis is (1) strongly inhibited by p21, (2) induced
      by bax, and (3) influenced by bcl-2, which, presumably, inhibits tumor cell
      apoptosis.

PMID- 14663637
TI  - Biweekly paclitaxel in patients with metastatic breast cancer.
AB  - BACKGROUND: This study was conducted to evaluate the efficacy and the toxicity of
      paclitaxel administered as a biweekly 1-h infusion (120 mg/m2). METHODS: Twenty
      patients with metastatic breast cancer were enrolled in this study. Paclitaxel
      was administered at a dose of 120 mg/m2 by an intravenous 1-h infusion every 2
      weeks. The primary objectives of the study were the response rate and toxicity.
      Pharmacokinetic analysis was conducted in 7 of the 20 patients treated with
      paclitaxel. RESULTS: Four of the 20 patients had grade 3 or 4 neutropenia.
      Arthralgia or myalgia was observed in 8 of the 20 patients. Grade 2 or 3
      neurotoxicity was observed in 6 of the 20 patients. In the 20 assessable
      patients, there was one complete response and eight partial responses. The
      overall response rate was 45%. The mean time to progression was 5.4 months.
      CONCLUSIONS: Biweekly paclitaxel may be suitable for patients receiving
      paclitaxel for palliative therapy, as tolerance was similar to that with the
      weekly schedule, but with the advantage of increased convenience.

PMID- 14663638
TI  - Lifestyle factors associated with atrophic gastritis among Helicobacter pylori
      seropositive Japanese-Brazilians in Sao Paulo.
AB  - BACKGROUND: Studies of lifestyle factors related to gastric atrophy development
      in Helicobacter pylori-infected individuals are limited. The present cross
      sectional study aimed to examine the associations between lifestyle factors and
      serum pepsinogens (PGs) among anti- H. pylori antibody-seropositive Japanese in
      Brazil, where gastric cancer mortality was reported to be as high as in Japanese
      in Japan, and seropositive individuals were still frequently detected. METHODS:
      The subjects were 291 seropositive individuals (129 males and 162 females; age,
      30 to 69 years) out of 656 Japanese-Brazilian volunteers in Sao Paulo city.
      Information on lifestyle factors was obtained using a self-administered
      questionnaire. Atrophic gastritis was defined as a PG1 serum level less than 70
      ng/ml and PG1/PG2 ratio less than 3. RESULTS: The prevalence of atrophic
      gastritis was 31.9% (95% confidence intervals, 26.6%-37.6%). The proportion of
      subjects with atrophic gastritis increased with age, but there were no
      significantly marked differences in the proportions of subjects with atrophic
      gastritis among the three generations studied (first generation [Issei], second
      generation [Nisei], and third generation [Sansei]) for any 10-year age group. The
      associations with smoking and alcohol drinking were not significant. Length of
      education was inversely associated with gastric atrophy, while infrequent rice
      intake was preventive; the odds ratio relative to everyday rice intake was 0.13
      (95% confidence intervals, 0.39-0.46) on multivariate analysis. CONCLUSIONS: The
      present study demonstrated that frequent rice intake was a risk factor for
      atrophic gastritis among the H. pylori-infected Japanese-Brazilians, suggesting
      that diet including rice plays a role in the step from H. pylori infection to
      gastric atrophy.

PMID- 14663639
TI  - Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder
      cancer after transurethral resection.
AB  - BACKGROUND: In a prospective study we compared the usefulness of urinary nuclear
      matrix protein 22 (NMP22) with that of urine cytology and other urinary markers
      in the monitoring of superficial bladder cancer after transurethral resection
      (TURBT). METHODS: The subjects were 156 patients, comprising 99 patients with
      superficial bladder cancer in whom TURBT was planned (untreated group) and 57
      patients without tumors in the bladder who had been followed up after TURBT
      (follow-up group). RESULTS: Among the 156 patients, who were monitored for 11-26
      months (median, 21 months), recurrence was observed in 51 patients (33.0%). At
      the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and
      bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%,
      and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor
      size and urinary WBC. The size of recurrent tumors was significantly smaller
      (P<0.05) than that of the initial tumors. Based on receiver operating
      characteristic (ROC) curves calculated from the data of patients with recurrence,
      the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22
      and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and
      BFP were 48.8% and 44.2%, respectively. CONCLUSIONS: Because the size of
      recurrent bladder tumors is usually smaller than that of the initial tumors, the
      cutoff values of urinary markers should be reduced to detect these tumors. We
      recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of
      bladder tumor.

PMID- 14663640
TI  - Phase I study of irinotecan and S-1 combination therapy in patients with
      metastatic gastric cancer.
AB  - BACKGROUND: Irinotecan plus intravenous 5-fluorouracil with leucovorin is
      effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine
      derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine
      (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an
      orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1 : 0.4 : 1. S
      1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I
      study was conducted to assess the maximum tolerated dose and the recommended dose
      of the combination of irinotecan and S-1. METHODS: Irinotecan was given
      intravenously over the course of 90 min on day 1 and S-1 was given orally from
      days 1 to 14 of a 21-day cycle. The dose of S-1 was 80 mg/m2 per day, given in
      two divided doses. The dose of irinotecan was escalated in a stepwise fashion
      from 100 mg/m2 (level 1; n = 3), to 125 mg/m2 (level 2; n = 3), and 150 mg/m2
      (level 3; n = 6). RESULTS: Dose-limiting toxicity did not occur during cycle 1,
      and the recommended dose for phase II studies was determined to be level 3, which
      was associated with grade 3 diarrhea in one patient, and with refusal to continue
      treatment because of prolonged fatigue in two patients. Grade 3 neutropenia
      developed in one of three patients at level 1 and level 2, and in two of six
      during cycle 1 of level 3. The recommended dose was determined to be 150 mg/m2 of
      irinotecan on day 1 and 80 mg/m2 per day of S-1 on days 1 to 14 of a 21-day
      cycle. Five of seven patients with measurable lesions had a partial response.
      CONCLUSIONS: A combination of irinotecan and S-1 can be recommended for further
      phase II studies in patients with gastric cancer.

PMID- 14663641
TI  - Modified pharmacokinetic modulating chemotherapy using 5-fluorouracil, UFT, and
      taxotere (docetaxel) for advanced gastric cancer.
AB  - The efficacy of neoadjuvant chemotherapy for advanced gastric carcinoma is
      controversial. Moreover, a standard regimen for such chemotherapy has not been
      clearly established. Pharmacokinetic modulating chemotherapy (PMC), a combination
      of infused 5-fluorouracil and oral uracil-tegafur, has been proven to be highly
      effective for the treatment of colorectal carcinoma. We report two patients with
      advanced gastric carcinoma successfully treated with PMC and infused taxotere
      (TXT; docetaxel). Preoperative treatment with PMC and TXT significantly decreased
      the depth of wall penetration of the tumor in one patient and reduced the size of
      the tumor in the other patient. In both patients, there were significant
      chemotherapeutic effects on the primary tumor and on regional lymph nodes
      pathologically. Preoperative PMC plus TXT produced primary tumor downstaging,
      leading to improved resectability. The responsiveness of metastatic cancer cells
      in the regional lymph nodes suggested the possibility of nodal downstaging by
      this regimen.

PMID- 14663642
TI  - Primary sebaceous carcinoma of the lacrimal gland treated by carbon ion
      radiotherapy.
AB  - Sebaceous carcinoma is a rare primary neoplasm of the lacrimal gland and, to the
      best of our knowledge, only six cases have been reported previously. Sebaceous
      carcinoma of the orbit more commonly occurs as secondary invasion from the
      eyelid, but may occur by way of metastatic spread from elsewhere in the body. We
      describe a patient who presented with a rapidly growing neoplasm of the lacrimal
      gland which, histologically, was a sebaceous carcinoma. The eyelid was entirely
      normal on examination. In this patient we found a single tumor cell line within
      the normal lacrimal gland. In this article we describe the diagnosis and
      treatment with carbon ion radiotherapy of primary sebaceous carcinoma of the
      lacrimal gland, a condition not previously reported in Japan.

PMID- 14663643
TI  - Allogeneic bone marrow transplantation in a patient with T-prolymphocytic
      leukemia with small-intestinal involvement.
AB  - Although T-prolymphocytic leukemia (T-PLL) is characterized by organ
      infiltration, small-intestinal involvement is rare. We performed an unrelated
      allogeneic bone marrow transplantation in a patient with T-PLL who had multiple
      lymphomatous polyposis of the small intestine refractory to combination
      chemotherapy (cyclophosphamide, vincristine, and prednisolone [COP] and
      fludarabine plus cyclophosphamide). The patient developed no graft-versus-host
      disease (GVHD) and remains in complete remission 16 months after the
      transplantation. T-PLL is usually refractory to chemotherapy and is a T-cell
      malignancy with poor prognosis. There have been several reports on allogeneic
      hematopoietic stem-cell transplantation (allo-HSCT) for T-PLL, but none on allo
      HSCT for T-PLL patients with intestinal involvement. It is suggested that allo
      HSCT may improve the prognosis in patients with T-PLL involving the small
      intestine.

PMID- 14663644
TI  - Development of severe complications caused by stent placement followed by
      definitive radiation therapy for T4 esophageal cancer.
AB  - Esophageal stenting in previously irradiated patients is known to cause more
      severe complications than those in patients who were not irradiated. But there
      are few reports regarding the results of stent placement before radiation
      therapy. Three patients with stage T4 esophageal cancer with direct invasion to
      the trachea and/or aorta underwent radiation therapy after stent placement. Two
      of the three patients had received systemic chemotherapy before radiation
      therapy. Fifty-one to 66 Gy of radiation therapy was administrated 15 to 66 days
      after the stent placement. The initial response to radiation therapy was no
      change (NC) or progressive disease (PD). All patients died of bleeding or
      pneumonia caused by perforation at the site of the stents 17 to 79 days after the
      radiation therapy. It is strongly suggested that even in patients with locally
      advanced esophageal cancer with severe dysphagia, radiation therapy should
      precede stent placement, because the consequences of radiation therapy after
      stent placement are devastating, and radiation therapy alone can, potentially,
      resolve the symptoms.

PMID- 14663645
TI  - A young woman with clear cell adenocarcinoma of the uterine cervix.
AB  - In May 1999, an 18-year-old woman visited a physician because of vaginal bleeding
      and the excretion of large clots from the vagina. A vaginal tumor was discovered
      and the patient was referred to our outpatient department. Vaginal examination
      showed a bleeding, tumor, approximately 6 cm in size, protruding from the
      cervical os and filling the vagina. The cytological finding of the uterine cervix
      was class V, and the histological diagnosis by punch biopsy was clear cell
      adenocarcinoma (CCAC) of the uterine cervix. The patient initially received
      neoadjuvant chemotherapy (NAC) with intraarterial injections of 8 mg/m(2) of
      mitomycin, 270 mg/m(2) of etoposide, and 380 mg/m(2) of carboplatin. Although the
      NAC reduced the size of the tumor, it failed to produce favorable pathological
      changes and was therefore deemed ineffective. A radical abdominal hysterectomy
      and pelvic lymphadenectomy were performed on October 12. Macroscopic findings
      showed a tumor, 6 cm in diameter, growing from the right side of the uterine
      cervix, with a fragile, necrotic surface. Pathological diagnosis was CCAC of the
      cervix (pT2a, N0, M0). The patient was discharged from our hospital without any
      postoperative chemotherapy or radiation therapy. No signs of recurrence have been
      detected since. We reviewed the literature on CCAC patients in Japan up to the
      present and compared the data with the data reported in a review of CCAC in the
      Netherlands. While there were similarities between the patients in the two
      countries in the patients' pattern of growth and the poor prognosis of the
      tumors, there was a significant difference between the countries in the patients'
      history of diethylstilbestrol (DES) exposure. These results suggest that menarche
      and menopause may play roles in promoting carcinogenesis, or alternatively, that
      a subpopulation of women are subject to genetic or exogenous risk factors other
      than DES.

PMID- 14663646
TI  - Human health implications of avian influenza viruses and paramyxoviruses.
AB  - Among avian influenza viruses and avian paramyxoviruses are the aetiological
      agents of two of the most devastating diseases of the animal kingdom: (i). the
      highly pathogenic form of avian influenza, caused by some viruses of the H5 and
      H7 subtypes, and (ii). Newcastle disease, caused by virulent strains of APMV type
      1. Mortality rates due to these agents can exceed 50% in naive bird populations,
      and, for some strains of AI, nearly 100%. These viruses may also be responsible
      for clinical conditions in humans. The virus responsible for Newcastle disease
      has been known to cause conjunctivitis in humans since the 1940s. The
      conjunctivitis is self-limiting and does not have any permanent consequences.
      Until 1997, reports of human infection with avian influenza viruses were sporadic
      and frequently associated with conjunctivitis. Recently, however, avian influenza
      virus infections have been associated with fatalities in human beings. These
      casualties have highlighted the potential risk that this type of infection poses
      to public health. In particular, the pathogenetic mechanisms of highly pathogenic
      avian influenza viruses in birds and the possibility of reassortment between
      avian and human viruses in the human host represent serious threats to human
      health. For this reason, any suspected case should be investigated thoroughly.

PMID- 14663647
TI  - Spontaneous cervical osteomyelitis due to Yersinia enterocolitica in a non
      immunocompromised host.

PMID- 14663648
TI  - Spectroscopic and computational characterization of the nickel-containing F430
      cofactor of methyl-coenzyme M reductase.
AB  - Methyl-coenzyme M reductase (MCR) catalyzes the terminal reaction in
      methanogenesis, the formation of methane from methyl-coenzyme M and coenzyme B.
      The active site of MCR binds the prosthetic group F(430), a unique nickel
      hydrocorphin cofactor. Here, spectroscopy and computations are employed in
      developing detailed electronic descriptions of the Ni(II) and Ni(I) forms of the
      free cofactor. Absorption, magnetic circular dichroism (MCD), and variable
      temperature variable-field MCD data are analyzed within the framework of time
      dependent DFT computations to assign key electronic transitions. DFT calculations
      are further employed to evaluate possible reduced F(430) models-a one-electron
      reduced Ni(I)F(430) model and a three-electron reduced Ni(I)F(red430) model
      (possessing a reduced hydrocorphin ligand)-on the basis of excited-state spectra
      and published EPR/ENDOR parameters. While calculations on both models yield
      spectroscopic parameters that are consistent with most experimental data, overall
      better agreement is achieved using the Ni(I)F(430) model, particularly with
      respect to electronic absorption and (1)H ENDOR. The experimentally validated
      bonding descriptions generated herein show that in Ni(II)F(430) the occupied Ni
      3d orbitals are too low in energy to significantly perturb the dominant
      electronic transition involving the pi and pi* frontier MOs of the macrocycle
      (i.e., the HOMO-->LUMO transition). Upon one-electron reduction of the Ni(II)
      ion, the occupied Ni 3d orbitals are raised in energy, shifting between the HOMO
      and the LUMO of the oxidized cofactor. These ground-state changes have a dramatic
      effect on the excited-state structure, causing a blue shift of the dominant pi-
      >pi* transition and the appearance of numerous Ni 3d-->hydrocorphin pi* charge
      transfer features in the vis/near-IR region.

PMID- 14663649
TI  - Simulating large nuclear quantum mechanical corrections in hydrogen atom transfer
      reactions in metalloenzymes.
AB  - The role of nuclear quantum mechanical effects in enzyme catalysis has recently
      attracted significant interest both from theoretical and experimental points of
      view. From a theoretical point of view, it is undoubtedly a challenge to try to
      account for the observed tunneling in the protein by microscopic simulations
      without adjustable parameters. One of the most spectacular examples of nuclear
      quantum mechanical effects is the reaction of lipoxygenase, which is
      characterized by a very large kinetic isotope effect and, thus, provides an
      excellent benchmark for simulation approaches. In the present study, we report a
      microscopic simulation of the large kinetic isotope effect in soybean
      lipoxygenase and its temperature dependence. This is, to the best of our
      knowledge, the first time that a very large nuclear quantum mechanical
      contribution to the activation free energy of a hydrogen atom transfer reaction
      and its temperature dependence have been evaluated by microscopic simulation. The
      simulation reproduces quite well the experimental kinetic information and the
      corresponding difference between the classical and quantum mechanical activation
      free energies for the H and D transfer reactions.

PMID- 14663650
TI  - Synthetic analogues of the histidine-chlorophyll complex: a NMR study to mimic
      structural features of the photosynthetic reaction center and the light
      harvesting complex.
AB  - Mg(II)-porphyrin-ligand and (bacterio)chlorophyl-ligand coordination interactions
      have been studied by solution and solid-state MAS NMR spectroscopy. (1)H, (13)C
      and (15)N coordination shifts due to ring currents, electronic perturbations and
      structural effects are resolved for imidazole (Im) and 1-methylimidazole (1-MeIm)
      coordinated axially to Mg(II)-OEP and (B)Chl a. As a consequence of a single
      axial coordination of Im or 1-MeIm to the Mg(II) ion, 0.9-5.2 ppm (1)H, 0.2-5.5
      ppm (13)C and 2.1-27.2 ppm (15)N coordination shifts were measured for
      selectively labeled [1,3-(15)N]-Im, [1,3-(15)N,2-(13)C]-Im and [1,3-(15)N,1,2
      (13)C]-1-MeIm. The coordination shifts depend on the distance of the nuclei to
      the porphyrin plane and the perturbation of the electronic structure. The signal
      intensities in the (1)H NMR spectrum reveal a five-coordinated complex, and the
      isotropic chemical shift analysis shows a close analogy with the electronic
      structure of the BChl a-histidine in natural light harvesting 2 complexes. The
      line broadening of the ligand responses support the complementary IR data and
      provide evidence for a dynamic coordination bond in the complex.

PMID- 14663651
TI  - Hypericum perforatum subspecies angustifolium shows a protective activity on the
      consequences of unavoidable stress exposure at lower doses than Hypericum
      perforatum perforatum.
AB  - Clinical studies have demonstrated that the antidepressant efficacy of Hypericum
      perforatum extract is comparable to that of classic antidepressants, such as
      imipramine. The role played by its components, particularly hypericin and
      hyperforin, has been examined in different experimental models of depression. The
      present study was carried out in order to verify the hypothesis that hyperforin
      is the main active antidepressant component. For this purpose we evaluated the
      activity of a dry extract from a subspecies of H. perforatum, H. perforatum spp.
      angustifolium, which has a higher hyperforin content than H. perforatum
      perforatum, in a series of experimental models of depression. The models used are
      based on the development of hyporeactivity to aversive stimuli induced by
      unavoidable stress exposure in rats. The extract of H. perforatum angustifolium
      presented an efficacy that was similar to that obtained with a treatment with
      imipramine or H. perforatum perforatum. Furthermore, in the models used the H.
      perforatum angustifolium extract was active at doses eight times lower than those
      necessary to produce a comparable activity with H. perforatum extract.

PMID- 14663652
TI  - Public attitudes towards treatment of depression: effects of an information
      campaign.
AB  - In 2000 and 2001, telephone surveys in the German cities Nuremberg and Wurzburg
      were carried out to gain insights into beliefs and attitudes of the public
      towards depression and its treatment and to evaluate the activities of the
      "Nuremberg Alliance Against Depression", a joint effort of health professionals,
      aiming at the improvement of the situation of people in Nuremberg suffering from
      depression. In 2000, most people considered depression a serious illness that can
      be treated fairly well by a professional. Concerning the proper means for this,
      we found that the well-known bad reputation of psychotropic drugs still prevails.
      Since 2001 a prominent part of the activities of the Nuremberg Alliance is a
      citywide campaign informing the public about causes and treatment of depression.
      Although the campaign had been performed for only 10 months, slight to moderate
      effects concerning causes and treatment of depression were observed in both
      cities. However, no effects were found with respect to the misconceptions about
      pharmacotherapy.

PMID- 14663653
TI  - Effects of chronic haloperidol and clozapine treatment on AMPA and kainate
      receptor binding in rat brain.
AB  - BACKGROUND: Alterations in AMPA and kainate receptor binding have been revealed
      in post-mortem schizophrenic brains. As most patients had been treated with
      antipsychotics, medication effects cannot be excluded as a possible explanation
      for these results. METHODS: Within the framework of this animal study, we
      investigated [3H]AMPA and [3H]kainate receptor binding in different rat brain
      regions following 6 months of oral treatment with either haloperidol (1.5
      mg/kg/day) or clozapine (45 mg/kg/day). RESULTS: AMPA receptor binding was
      increased after haloperidol treatment in the striatum, nucleus accumbens,
      cingulate cortex, and insular cortex. Clozapine showed increased AMPA receptor
      binding only in the anterior cingulate cortex. Kainate receptor binding was
      increased by both drugs in all hippocampal subfields. CONCLUSIONS: This altered
      receptor binding may be related to beneficial neuroleptic effects and side
      effects. Furthermore, neuroleptic therapy may contribute to some of the post
      mortem findings in the striatum in schizophrenia.

PMID- 14663654
TI  - Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week,
      multi-center, double-blind, placebo-controlled, randomized trial.
AB  - In 1996, Kanowski et al. reported about the beneficial effects of ginkgo biloba
      special extract EGb 761 (240 mg/day) in outpatients with pre-senile and senile
      primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct
      dementia (MID) of mild to moderate severity. The comparison of the results of
      this double-blind, placebo-controlled, randomized, multi-center study with other
      dementia studies is hampered by the fact that only the responder analysis of the
      per-protocol (PP) population, which was pre-specified in the protocol as
      confirmatory analysis, has been published in detail so far. Moreover, cognitive
      functioning was measured using the Syndrom-Kurztest (SKT), whereas results of
      other studies are based on the Alzheimer's Disease Assessment Scale-Cognitive
      Subscale (ADAS-cog). Therefore, the conventional intention-to-treat (ITT)
      analysis of this study is provided with an estimation of ADAS-cog scores based on
      measured SKT scores. After 24 weeks of treatment, the ITT analysis of the SKT and
      estimated ADAS-cog scores revealed a mean decrease in the total score by -2.1 (95
      % CI: -2.7; -1.5) points and -2.7 (95 % CI: -3.5; -1.9) points, respectively, for
      the EGb 761 group, which indicates an improvement in cognitive function. On the
      contrary, the placebo group exhibited only a minimal change of -1.0 (95 % CI: 
      1.6; -0.3) and -1.3 (95 % CI: -2.0; -0.4) points, respectively. The changes from
      baseline differed significantly between treatment groups by 1.1 (SKT) and 1.4
      (estimated ADAS-cog) points, respectively (P = 0.01). The Clinical Global
      Impression of Change (CGI, Item 2) favored the EGb 761 group with a mean
      difference of 0.4 points (P = 0.007). Changes in the rating related to activities
      of daily living (Nurnberger-Alters-Beobachtungs-Skala, NAB) showed a favorable
      trend for EGb 761R. A subgroup analysis regarding patients with DAT yielded
      comparable results. Using a decrease of at least 4 points on the estimated ADAS
      cog scores as cutoff criterion for treatment response, 35 % of EGb 761-treated
      patients were considered responders versus only 19 % for the placebo group (P =
      0.01). The results of this ITT analysis substantiate the outcomes previously
      obtained with a responder analysis of the per-protocol population and confirm
      that EGb 761 improves cognitive function in a clinically relevant manner in
      patients suffering from dementia. The therapeutic effect is in line with the
      outcome of another EGb 761 study conducted in the U.S.

PMID- 14663655
TI  - Short-term effects of acetylcholinesterase inhibitor treatment on EEG and memory
      performance in Alzheimer patients: an open, controlled trial.
AB  - INTRODUCTION: Acetylcholinesterase inhibitor treatment enhances cholinergic
      neurotransmission and may thus partially reverse EEG slowing and memory
      impairment in Alzheimer patients within short time. METHODS: We studied the short
      term effects of treatment with either rivastigmine or donepezil on EEG and memory
      performance in a group of 35 Alzheimer patients in an open, controlled design.
      RESULTS: Under a 1- or 2-week acetylcholinesterase inhibitor treatment, a
      decrease of global theta power and an improvement in the ADAS memory score were
      observed. However, compared to the control condition, only the theta power
      decrease remained significant and can be definitely considered a medication
      effect. DISCUSSION: EEG spectral analysis could be shown to rapidly reflect the
      cerebral cholinergic action of short-term acetylcholinesterase inhibitor
      treatment. Whether this action is related to the therapeutic efficacy of this
      type of drug must be determined in further longitudinal studies.

PMID- 14663656
TI  - Are patients with schizophrenia under-treated with second-generation
      antipsychotics? A pilot study of the prescription practices of German
      psychiatrists.
AB  - INTRODUCTION: Patients' and relatives' associations, psychiatrists, and
      pharmaceutical companies are complaining about a deficiency in the care of
      psychiatric patients with innovative medications in Germany. They estimate that
      only about 10- 30 % of all patients with schizophrenia receive second-generation
      antipsychotics, a figure that lies significantly below the international average.
      METHODS: In order to determine the frequency of use of second-generation
      antipsychotics in the actual care of schizophrenic patients, we conducted the
      following investigations:--Discharge papers of schizophrenic inpatients from a
      university hospital and from a district hospital were studied with regard to the
      antipsychotic discharge medication.--Practicing psychiatrists were contacted and
      asked whether during the first 3 months after discharge they had continued the
      antipsychotic discharge medication that was proposed by the hospital. RESULTS:
      The investigation of a total of 200 discharge papers and the subsequent
      questioning of the psychiatrists who carried out the follow-up treatment showed
      that 166 patients (83 %) received a second-generation antipsychotic upon
      discharge. Only 5 % of these patients were switched to conventional
      antipsychotics in the outpatient treatment. Thus, contrary to our expectations,
      there was no noteworthy change from second-generation to classical
      antipsychotics. DISCUSSION: Therefore, in the sample analyzed the second
      generation antipsychotics were far more frequently prescribed than would have
      been expected according to general estimates, and it was not possible to verify
      the often-heard complaints of an under-treatment with second generations in this
      study. Our findings suggest, however, that only 60 % of the patients still
      receive their discharge medication 3 months after discharge from the hospital.
      This raises the important question as to how continuity of the antipsychotic
      treatment could be better ensured.

PMID- 14663657
TI  - The validity of the depression rating scales in discriminating between citalopram
      and placebo in depression recurrence in the maintenance therapy of elderly
      unipolar patients with major depression.
AB  - The World Federation of Societies of Biological Psychiatry guidelines for
      treatment of unipolar major depression has recommended three depression rating
      scales for evaluating outcome: The Hamilton Depression Rating Scale (HAM-D), the
      Montgomery-Asberg Depression Rating Scale (MADRS), and the Bech-Rafaelsen
      Melancholia Scale (MES). In this study we evaluated the ability of these scales
      to differentiate between citalopram and placebo in the recurrence prevention of
      unipolar depression. The study is a psychometric reexamination of a trial on the
      efficacy of citalopram versus placebo in the maintenance therapy of elderly
      patients with unipolar depression. Internal validity (the Cronbach coefficient
      alpha, the Loevinger coefficient of homogeneity, and factor analysis) of the
      three scales has been examined to evaluate their unidimensionality. In the
      outcome analysis for depression recurrence, the conventional cutoff scores of the
      three scales are used. In total, 60 patients received citalopram and 61 patients
      received placebo in the maintenance phase of 48 weeks. The results showed that
      the internal validity was higher for MES and MADRS than for HAM-D. Using the
      MADRS, 67.2 % of the patients on placebo and 31.6 % of the patients on citalopram
      developed a depression recurrence (ratio 2.12); using HAM-D17, 42.6 % on placebo
      and 13.3 % on citalopram developed a depression recurrence (ratio 3.20); and
      using the MES, 34.4 % on placebo and 11.7 % on citalopram developed a depression
      recurrence (ratio 2.94). The conventional cutoff scores of HAM-D17 and MES for
      depression recurrence indicated a ratio between citalopram and placebo of around
      3, while the conventional cutoff scores of MADRS for depression recurrence
      indicated a ratio of only around 2. In future trials on the recurrence prevention
      of unipolar depression, a cutoff score of 25 rather than 22 on the MADRS is
      recommended.

PMID- 14663658
TI  - Risperidone-induced marked elevation of serum creatine kinase in adolescence. A
      case report.
AB  - We report on a 17-year-old boy who developed a marked increase in serum creatine
      kinase (CK) (9743 U/l) during treatment with risperidone for catatonic psychosis.
      Known causes of elevated CK such as delirium, malignant neuroleptic syndrome,
      infection, cocaine overdose, trauma, and intramuscular injections were ruled out.
      Vital signs remained always within the normal range. On discontinuation of
      risperidone, serum CK concentrations returned to 105 U/l within 1 week and
      remained within normal limits. While a transient moderate increase in CK activity
      at admission may be related to acute psychosis, risperidone seems to be the
      causative agent for the later marked elevation. To our knowledge, this is the
      first reported case of risperidone-associated elevation of serum CK in an
      adolescent. While discontinuation of risperidone does not seem necessary in
      patients with a moderate increase of serum CK, withdrawal of neuroleptics is
      warranted in more severe cases.

PMID- 14663755
TI  - Glial line-derived neurotrophic factor (GDNF): Biological activities.
AB  - Glial cell line-derived neurotrophic factor (GDNF) was initially discovered as a
      neurotrophic factor that enhances survival of midbrain dopaminergic neurons.
      Findings in 1994 and 1995 extended the spectrum of biological activities of GDNF
      to different populations of neurons (motor and sensory). Recent findings revealed
      that GDNF, Neurturin (NTN), Persephin (PSP), and Artemin (ARTN) are members of
      the GDNF protein family and are structurally related to transforming growth
      factor protein family. They are survival factors for peripheral and central
      neurons, for oligodendrocytes and can promote morphogenesis of kidney in vitro.

PMID- 14663756
TI  - Topographical relationship of the amygdaloid body to the hippocampal formation
      and lateral ventricle - MRI study.
AB  - The relationship of the amygdaloid body to the hippocampal formation and lateral
      ventricle was studied on MRI slabs of brains of 25 volunteers. Considering the
      presence of the hippocampal formation and/or uncal sulcus on a cross-section
      three segments of the amygdaloid body were distinguished in rostro-caudal order:
      prehippocampal, suprahippocampal anterior (preuncal) and suprahippocampal
      posterior (uncal), each one presenting characteristic features. The lengths of
      the amygdaloid body and of its segments were calculated. In each segment the
      great variability of the topographical relations was found. Especially in the
      suprahippocampal anterior segment the relation of the lateral ventricle to both,
      the amygdaloid body and hippocampus shows great differences, even between the
      right and left side.

PMID- 14663757
TI  - The timing and sequence of appearance of the distal branches of the human
      embryonic vestibular ganglion.
AB  - Vestibular ganglion was investigated in human embryos during developmental stages
      l3-23 (34-56 postovulatory days). Branches of the vestibular ganglion forming
      ampullar nerves were observed in ernbryos at stage I5. During the last embryonic
      stages (stage 22 and 23) the utriculo-ampullar, posterior ampullar, and saccular
      nerves were clearly distinguished.

PMID- 14663758
TI  - Veins with saccular dilatations in gastric mucosa of the rat.
AB  - It is well known that blood from the gastric mucosa of the rat is drained by
      collecting veins (venules). The aim of this study was to describe hitherto
      unrecognized saccular dilatations connected with these vessels. Rats received
      atropine or papaverine l h before ligation of the portal vein, Stomachs fixed in
      formaldehyde were prepared in toto after clearing in methyl salicylate or
      processed by standard histological technique. A single stomach contained about
      1000 connecting veins localized exclusively in the oxyntic mucosa. After
      administration of relaxing agents and portal vein ligation the collecting veins
      were enlarged and in 80 percent of them one to three sacculi filled with blood
      could be seen. Histological observations shown that collecting veins empty into
      veins running between lamina muscularis and lamina propria mucosae. Sacculi were
      partially separated from the lumen of the collecting vein by a tissue band. In
      view of the relaxing effect evoked by atropine the veins and their sacculi appear
      to be under vagal control. Conceivably, their alternate expansion and collapse
      could facilitate movement of glandular content to the surface of the stomach
      and/or movement of interstitial fluid between cells.

PMID- 14663759
TI  - The caudal intercarotid artery in species of order perissodactyla.
AB  - The caudal intercarotid artery was investigated in 6 species of Equidae family
      and in lowland tapir of Tapiridae family. It was found that this artery connects
      bilateral intracranial segments of the internal carotid artery. It is located in
      the cavernous and intercavernous sinuses, caudal to the hypophysis. This artery
      being constant vessel in horse, is also permanent vessel in other species of
      Equidae family. It is homologous with anastomising vessel in fishes, amphibia,
      reptiles and birds.

PMID- 14663760
TI  - Variability of posterior veins of the left ventricle in the adult human heart.
AB  - The frequency of occurrence and topography of the outfow portions of the
      posterior veins of the left ventricle were observed. One hundred fifty adult
      human hearts of both sexes from l8 to 85 years of age fixed in a formalin/ethanol
      solution were examined. Classical macroscopic anatomical examination methods were
      used. The posterior veins of the left ventricle were always present in the
      examined heart material, but occurred in varying number (l -4). The outfow
      portions of these veins were characterized by significant variation with regards
      to position as well as angle of its outfow.

PMID- 14663761
TI  - The arterial vascularization of the stomach fundus of human fetuses.
AB  - We have investigated the existence, frequency and the course of arteries of the
      human stomach fundus by injection method. Our material obtained 52 human fetuses
      of the length range from 127 to 285 mm and the fetal age range from l5 to 28
      weeks of gestation. It has been found, that the source of the arterial blood
      supply of this region are two arteries: the left gastric artery and splenic
      artery with its bigger branches: posterior gastric artery, superior polar artery
      and short gastric arteries. The source of arterial blood supply of the stomach
      fundus there have been two in 6 cases (11,5%) or three in 45 cases (86,6%) or
      four in 1 case (l,9%) of these arteries. We have analysed in detail the
      contribution and the range of the following arteries in the stomach quadrants. It
      has been shown, that the anterior medial quadrant has the best arterial blood
      supply and the anterior lateral has the worst one.

PMID- 14663762
TI  - Facial artery and atherosclerosis.
AB  - We have performed a study about the incidence of the atherosclerotic phenomenon
      in the human facial artery, having observed an increase with aging. We also have
      researched the role of the smooth muscle cells in its genesis, with
      morphological, ultrastructural and immunohistochemical techniques.

PMID- 14663763
TI  - Formation of the nemaline structures in soleus muscle of rats subjected to long
      lasting immobilization.
AB  - We performed the ultrastructural evaluation of presence and of some basic
      morphometric parameters of nemaline structures (NS) and Z band malformations in
      the musculus soleus fibres of rats kept in 7 months lasting immobilisation.
      Disturbances in Z band, leading to NS formation, were observed very often. Also
      numerous, classically rod-shaped NS were found in analyzed material. We
      demonstrate, for the first time in literature, that long-lasting hypokinesia
      induces NS formation. The pictures obtained may suggest successive steps in NS
      formation and maturation.

PMID- 14663764
TI  - Development of frontal sinus in human fetuses as seen in computerized tomography.
AB  - Using computerized tomography 7 human fetuses were examined, aging 24 to 39
      weeks. Frontal sinus developes in the region of frontal recess of the frontal
      nasal meatus in a fetus aging 27 weeks. In the latter weeks of the fetal life the
      frontal recess of the middle nasal meatus transforms upwards into an oval thin
      walled space corresponding to the developing frontal sinus. It adheres to the
      ethmoidal slabyrinth, integrating with it.

PMID- 14663765
TI  - Morphometric studies on rat testes in the course of postnatal development.
AB  - Computer-assisted analysis of histologic images of rat testis in the course of
      postnatal period demonstrated its stepwise development. Three stages of the
      development could be distinguished, associated with different number of Leydig
      cells and with distinct secretive activity of the cell, as reflected by serum
      testosterone levels.

PMID- 14663766
TI  - Number of valves in superficial veins of the leg.
AB  - Study was performed on 83 great and 64 small saphenous veins obtained from human
      adults males and females, aged 26 to 85 years. The number of valves in the great
      saphenous veins varies from 3 to l3, and in the small saphenous veins the number
      of valves varies from 1 to 8. The mean number of valves in the femoral part of
      the great saphenous veins is 5 and in the crural part of this vein is 3. The
      number of valves is not related to the length of vein.

PMID- 14663767
TI  - Prof. Jan Mikusek - obituary.

PMID- 14663774
TI  - Cardiac effects of adjuvant therapy for early breast cancer.
AB  - Adjuvant chemotherapy is an established standard of care for most patients
      diagnosed with early breast cancer, and its popularity is gaining worldwide. The
      systemic armamentarium presently includes anthracyclines and taxanes, alkylating
      agents, fluoropyrimidines, and antimetabolites; in the future, it may include
      platinum compounds and the recombinant humanized anti-HER2 monoclonal antibody,
      trastuzumab, as well. Anti-estrogens continue to play an important role in the
      adjuvant setting for hormone-sensitive primary breast cancer. Adjuvant
      radiotherapy is common in the setting of early-stage disease as breast
      conservation gains popularity, and radiation is often employed in the
      postmastectomy setting as well. As treatment guidelines continue to evolve with
      newer data, the relative benefits of treatment in many situations continues to
      grow. Refinement of the optimal identification of patients at risk for local and
      distant relapse is a continued challenge facing the treating clinician. Parallel
      to this effort, and of equal importance, is the ability to shield patients that
      will gain little, if any, benefit from treatment and to identify those who may be
      at greater risk to suffer from potential toxicities. Until these factors are
      better defined, the recognition by clinicians of long-term side effects
      associated with adjuvant therapy is obligatory. Acute toxicities from treatment
      are often reversible, but late onset adverse effects of therapy can increase
      morbidity and mortality in long-term survivors, and continue to be of concern.
      One of the most serious side effects of adjuvant therapy of early breast cancer
      is cardiac toxicity. This article will provide an overview of the cardiac effects
      of adjuvant therapy in the treatment of early breast cancer.

PMID- 14663775
TI  - Second cancers after breast cancer treatment.
AB  - Breast irradiation, adjuvant chemotherapy, and tamoxifen are associated with an
      increased risk of second cancers that may manifest decades after treatment.
      Although very small, it is nonetheless important for clinicians and women to be
      aware of and to recognize the risk. Postmastectomy irradiation is associated with
      a slight increase in the risk of developing a sarcoma or lung cancer after a
      latency period of more than 10 years. However, the majority of information on
      radiation-associated cancers is derived from large tumor registries, which
      reflect outdated radiation treatment practices. Modern treatment approaches,
      which use lower fraction size (or dose) and limit the exposure of surrounding
      normal tissue to radiation, are less likely to cause radiation-associated
      cancers. Adjuvant chemotherapy is not associated with any detectable increased
      risk of solid tumors beyond that which occurs as the population ages. However,
      alkylating agents, such as cyclophosphamide, and the topoisomerase II inhibitors,
      doxorubicin and epirubicin, are associated with two types of cytogenetically
      distinct leukemias after adjuvant chemotherapy. The absolute risk of developing
      leukemia is lower by orders of magnitude than the improvement in breast cancer
      mortality that results from adjuvant chemotherapy. Tamoxifen is associated with a
      two- to threefold increase in the risk of developing endometrial cancer, or about
      80 excess cases per 10,000 treated women at 10 years. The benefits of adjuvant
      therapy outweigh the risks of developing second cancers. Additional studies are
      needed to more precisely identify patients who are or are not likely to benefit
      from adjuvant therapy, and individual host and treatment factors that influence
      the development of second cancer.

PMID- 14663776
TI  - The impact of adjuvant therapy for breast cancer on cognitive function: current
      evidence and directions for research.
AB  - Available evidence supports the hypothesis that adjuvant chemotherapy for breast
      cancer can produce cognitive deficits, and that these deficits may have a
      significant impact on patients' quality of life. Studies have generally compared
      the results of a variety of cognitive measures performed following treatment to
      standardized population-based norms or to cancer patients who received local
      therapy, rather than to the individual's baseline level of functioning. Several
      longitudinal studies are in progress or in the planning stages to better quantify
      and understand the incidence and impact of cognitive effects of adjuvant
      chemotherapy, and to identify possible susceptibility factors in subgroups.
      Although the neurocognitive changes appear to be subtle, there may be enough data
      to consider discussing the possibility of cognitive dysfunction as an adverse
      effect when assessing the risks and benefits of adjuvant chemotherapy. Likewise,
      as the aromatase inhibitors are increasingly given to larger numbers of women in
      the adjuvant setting, it will be important to understand the cognitive impact of
      estrogen deprivation. Finally, there is interest in examining supportive
      pharmacologic or behavioral measures that might prevent or decrease cognitive
      effects in this setting. Herein, the data on cognitive changes associated with
      chemotherapy for breast cancer, current and future research directions, as well
      as possible treatments are reviewed.

PMID- 14663777
TI  - Osteopenia and osteoporosis in women with breast cancer.
AB  - Osteopenia and osteoporosis are prevalent in women. Epidemiologic studies show
      that the risk of breast cancer is greater in postmenopausal women with higher
      bone mineral density (BMD). Standard treatments for breast cancer such as
      adjuvant chemotherapy or hormonal therapy can increase bone loss, and hence may
      increase the risk of osteoporosis. Premenopausal women treated with standard
      adjuvant chemotherapy frequently develop permanent ovarian failure, or early
      menopause. Ovarian failure is associated with accelerated bone loss, and
      bisphosphonates may mitigate this bone loss in women treated with adjuvant
      chemotherapy. Tamoxifen preserves BMD in postmenopausal women; however, in
      premenopausal women tamoxifen may increase bone loss. Anastrazole, an aromatase
      inhibitor, is approved for adjuvant treatment of postmenopausal women with early
      stage, estrogen receptor-positive breast cancer. With a follow-up duration of
      less than 5 years, anastrazole-treated women experience increased fractures
      relative to those treated with tamoxifen. The management of osteopenia and
      osteoporosis in women with breast cancer generally does not differ from women
      without breast cancer. Adequate dietary calcium and vitamin D intake, encouraging
      weight-bearing exercise, and counseling about the relationship between smoking
      and alcohol and bone loss are all prudent recommendations for overall health and
      may lessen bone loss and the risk of subsequent osteoporosis. BMD should be
      measured in women with chemotherapy-induced ovarian failure, and in those on
      aromatase inhibitors. Bisphosphonates reduce the bone loss associated with
      chemotherapy-induced ovarian failure, and clinical trials evaluating third
      generation bisphosphonates in women with chemotherapy-induced ovarian failure are
      underway. As many women with breast cancer will be long-term survivors,
      increasing recognition of maintaining skeletal health is important.

PMID- 14663778
TI  - Estrogen deficiency symptom management in breast cancer survivors in the changing
      context of menopausal hormone therapy.
AB  - Vasomotor symptoms associated with menopause or cancer therapies represent an
      increasingly common problem for breast cancer survivors given the increasing use
      of ovarian suppression in premenopausal women and aromatase inhibitors in
      postmenopausal women. Although estrogen and/or progestin effectively reduce
      vasomotor symptoms, a recent Women's Health Initiative (WHI) randomized trial
      identified an unfavorable risk/benefit balance on life-threatening diseases,
      including increased breast cancer, for combined estrogen plus progestin use in
      otherwise healthy postmenopausal women. As a result, use of menopausal hormone
      therapy (MHT) for chronic disease risk reduction in any population cannot be
      supported. In addition, the safety of estrogen and/or progestin regarding risk of
      recurrence or new cancer development in breast cancer survivors has not been
      demonstrated. For vasomotor symptoms in this population, neuroendocrine agents,
      including selective seratonin reuptake inhibitors (SSRIs) or gabapentin, are
      reasonable choices with substantial impact on hot flashes and moderate toxicity
      profiles. When rigorously evaluated, most other nonhormonal pharmacologic and
      herbal interventions have been found to have either modest or no efficacy and/or
      limiting toxicity. In breast cancer survivors even local vulvar/vaginal symptoms
      are best treated by nonhormone products since drug absorption with systemic
      estrogen-like effects has been reported. Estrogen/progestin use in breast cancer
      survivors should be considered only for women with severe vasomotor symptoms
      refractory to other approaches after extensive informed decision-making including
      review of current Food and Drug Administration labeling concerns with use limited
      to the lowest dose and shortest duration possible.

PMID- 14663779
TI  - Nutrition-related issues for the breast cancer survivor.
AB  - Nutritional status and dietary intake play a significant role in the prognosis of
      breast cancer patients and may modify the progression of disease, as well as
      influence risk for comorbid conditions, such as osteoporosis and cardiovascular
      disease. A critical review of relevant clinical and epidemiological studies
      identified through MEDLINE and CINAHL searches was undertaken to provide the
      clinician with a summary of evidence that could form the appropriate guidance of
      women diagnosed with breast cancer who seek to reduce their risk of progressive
      or recurrent disease, and improve their overall health. Currently, healthy weight
      control with an emphasis on exercise to preserve or increase both lean body and
      bone masses, and plant-based diets that include ample amounts of nutrient-dense,
      low-energy density foods, particularly vegetables, can be recommended.
      Furthermore, diets high in vegetables, fruit, whole grains, and low-fat dairy
      foods, and low in saturated fat, may help to lower overall disease risk in this
      population.

PMID- 14663780
TI  - Psychosocial and sexual functioning of survivors of breast cancer.
AB  - The literature documents that the majority of breast cancer survivors have
      adjusted well after their first 2 years since diagnosis. However, there is a
      subset of survivors reporting psychological distress, including depression and
      anxiety, involving approximately 30% by 4 years post-treatment, but widely
      ranging from 5% to 50%, depending on when diagnosed and time since treatment
      completion. Further, a large proportion of survivors report cancer-related
      problems long after treatment completion, including cancer-related distress
      involving body image, fear of recurrence, post-traumatic stress disorder (PTSD),
      and sexual problems. Those with long-term medical sequelae, such as lymphedema,
      have worse adjustment compared to those who do not. Future research directions
      are suggested.

PMID- 14663781
TI  - Empowering women with breast cancer: one survivor's story.

PMID- 14663782
TI  - Follow-up care of breast cancer survivors.
AB  - Breast cancer survivors may have several medical and psychosocial concerns in
      follow-up care. Women with a history of breast cancer should be followed for
      local-regional recurrence or metastatic disease, as well as for the development
      of a second primary breast cancer in the contralateral breast. Regular follow-up
      visits can foster an ongoing patient-clinician relationship both to ensure
      adequate surveillance and so that symptoms of recurrence or complications of
      therapy will be reported by the patient and addressed promptly. There are
      multiple possible long-term complications that may arise following breast cancer
      treatment, many of which may be ameliorated with various therapies. Clinicians
      can also provide guidance and counseling as well as psychosocial support to
      patients regarding medical and psychosocial decisions that may be affected by
      their personal history of breast cancer.

PMID- 14663791
TI  - Valuing what is old and ancient.

PMID- 14663792
TI  - The pain of childbirth: perceptions of culturally diverse women.
AB  - The pain experiences of culturally diverse childbearing women are described based
      on a secondary analysis of narrative data from phenomenologic studies of the
      meaning of childbirth. Study participants were interviewed in the hospital after
      giving birth or in their homes within the first weeks after having a baby.
      Transcripts of interviews with childbearing women who lived in North and Central
      America, Scandinavia, the Middle East, the People's Republic of China, and Tonga
      were analyzed. Participants described their attitudes toward, perceptions of, and
      the meaning of childbirth pain. Culturally bound behavior in response to
      childbirth pain was also articulated. A variety of coping mechanisms were used by
      women to deal with the pain. Understanding the meaning of pain, women's
      perceptions of pain, and culturally bound pain behaviors is fundamental in order
      for nurses to facilitate satisfying birth experiences for culturally diverse
      women.

PMID- 14663793
TI  - Postoperative pain management on surgical wards-impact of database documentation
      of anesthesia organized services.
AB  - Postoperative pain management (POPM) should be based on an organization
      exploiting existing expertise and documenting the outcome of the POPM in each
      individual patient. The aims of the present study were to evaluate the adequacy
      of database documentation of POPM of an anesthesia organized, nurse-based,
      anesthesiologist-supervised acute pain service (APS) on surgical wards and to
      assess to what extent the information obtained was continuously used to improve
      practice. From 2890 registered cases in the database (patient controlled
      analgesia, n = 1975; epidural analgesia [EDA], n = 915), a homogeneous two-year
      sample of documentation charts from use of EDA for POPM in connection with major,
      open, abdominal surgical procedures (n = 381) was chosen for detailed analysis.
      The data charts contained information on patient data, drug dosage, total amount
      of infused drug, duration of EDA treatment, occurrence of side effects, and
      patient's level of satisfaction. The database information was easily accessible
      making assessment of relevant aspects of the routines, including associations
      between analgesic technique, patient related factors, and satisfaction with the
      services, immediately available. Only 58% of the data charts were properly
      completed and fed into the database but the clinical safety of the missing
      nondatabase documented sample was not found jeopardized. Although the database
      documentation routines were considered to fulfill basic requirements of data
      collection and monitoring of the appropriateness of POPM, they were not found to
      function optimally. The reason seemed to be inadequate feedback of information
      between the parties involved in the POPM services. The present study stresses the
      importance of establishing routines for adequate, continuous feedback of recorded
      audit data from the APS team to the surgical wards for the maintenance of a high
      level of compliance with accepted guidelines.

PMID- 14663794
TI  - The "write" way to get published in a professional journal.
AB  - This article describes each stage of the process of writing for professional
      publications. Tips for planning, writing, and submitting a publishable manuscript
      are discussed in detail. Specific guidelines that could improve acceptance of the
      manuscript are also outlined. Several tables provide information tailored to
      health care professionals who work in the areas of pain management, hospice, or
      palliative care.

PMID- 14663795
TI  - Accuracy of emergency nurses in assessment of patients' pain.
AB  - Pain is a common complaint in Emergency Departments. Inpatient studies have shown
      discrepancies between patients' and nurses' pain assessments. The accuracy of
      emergency nurse assessments of their patients' pain has not been well
      investigated. Using a 0 to 10 numeric rating scale (NRS), researchers asked
      patients to rate their pain intensity in triage. Separately, the triage nurse was
      asked to rate the patient's pain. This process was repeated with the same
      patients but different nurses after patients were taken back to a clinical area
      within the Emergency Department. At triage, patients' average pain intensity
      score was 7.5 +/- 2.2. The triage nurses' ratings were significantly lower at 5.1
      +/- 2.4 (p <.001). In the clinical area, patients' scores were also significantly
      higher than nurses' at 7.7 +/- 2.2 and 4.2 +/- 2.3, respectively (p <.001).
      Differences between nurses' and patients' pain intensity scores depended on the
      patient's chief complaint. Considerable underestimation of patient's pain
      occurred in both triage and in the clinical area. Underestimation of patient's
      pain can have negative effects if appropriate treatment is withheld. Minimizing
      patient-nurse discrepancies in pain intensity ratings through careful evaluations
      and acceptance of the patient's self report of pain are important first steps in
      improving pain management in the Emergency Department.

PMID- 14663800
TI  - Hemostasis is a shared responsibility.

PMID- 14663801
TI  - Types, frequencies, and risk factors for complications after third molar
      extraction.
AB  - OBJECTIVES: The study objective was to identify the types, frequency, and risk
      factors for complications after third molar (M3) extractions. STUDY DESIGN: This
      retrospective cohort study consisted of patients who had 1 or more M3s removed
      between 1996 and 2001. Risk factors were grouped into demographic, general
      health, anatomic, and operative. Outcome variables were operative or inflammatory
      complications. Data were analyzed using descriptive, bivariate, and multivariate
      statistics. RESULTS: The study sample was composed of 583 patients (57.0% male)
      with a mean age of 26.4 +/- 8.4 years. The overall complication rate was 4.6%.
      Increasing age, a positive medical history, and the position of the M3 relative
      to the inferior alveolar nerve were associated with an increased risk for
      complications. CONCLUSION: While age, medical history, and M3 anatomy cannot be
      altered directly, these factors may be modified indirectly, resulting in a
      potential decrease for postoperative complications.

PMID- 14663802
TI  - Primary management of maxillofacial hard and soft tissue gunshot and shrapnel
      injuries.
AB  - PURPOSE: A 10-year retrospective study was undertaken of all patients treated for
      facial gunshot and shrapnel wounds at our medical center to evaluate the outcomes
      and assess the results of simultaneous management to treat the hard and soft
      tissue injuries primarily. PATIENTS AND METHODS: A total of 44 patients were
      treated. Medical documentation of the patients was compiled. All maxillofacial
      gunshot, shrapnel, and warfare injuries were treated by the oral and
      maxillofacial surgeon. Other concomitant bodily injuries were treated by
      pertinent consultant specialists. Patients ranged in age from 8 to 53 years, with
      a mean age of 24.7 years. Maxillofacial hard and soft tissue injuries were
      treated definitively in the first operation except when gross contamination,
      infection, extensive comminution, or general condition precluded this. RESULTS:
      There were 2 shotgun, 28 bullet, 10 shrapnel, 3 land mine, and 1 breech block
      injuries. Overall postadmission mortality in this series was 2.2%. Of the 97.7%
      of the patients who had an injury to the underlying craniofacial skeleton, all
      required surgical intervention. The soft tissue and underlying bony injuries were
      addressed concomitantly (in a single stage at the time of primary surgical
      debridement) in 86.3% of the patients. Nine percent of the patients had a
      tracheostomy emergently for management of the airway, 6.8% had an intracranial
      injury, and 2.2% of them required neurosurgery. In the series, 4.5% of the
      patients had neck wounds that required exploration. Comprehensive treatment was
      rendered in 1 to 3 major operations (average, 1.5). CONCLUSION: All patients in
      this series required surgical intervention for treatment of their facial gunshot
      wounds. Primary treatment of hard and soft tissue injuries of the face at the
      time of surgical debridement was possible in the majority of our patients. This
      minimized the number of admissions and did not bear a higher complication rate
      than other reported series that advocate multiple staged operations to treat such
      injuries despite the fact that, in our series, flaps were also mobilized for
      wound closure in the primary phase.

PMID- 14663803
TI  - A bilateral musculomucosal buccal flap method for cleft palate surgery.
AB  - PURPOSE: This article introduces a new technique for the repair of cleft palate
      with a bilateral musculomucosal buccal flap. PATIENTS AND METHODS: From 1990 to
      2001, 26 patients with cleft palate of different types were treated for the
      repair of cleft palate with the bilateral musculomucosal buccal flaps. Their age
      ranged from 3 to 12 years (mean age, 6.4 years). They were followed up from 2 to
      8 years. The velopharyngeal closure was examined by nasopharyngoscopy. RESULTS:
      The postoperative results of all the patients who could be followed up were
      clearly satisfactory without any postoperative complications such as dehiscence
      or perforation or maxillary deformity. The velopharyngeal closure was
      satisfactory. CONCLUSION: Repair of cleft palate with bilateral musculomucosal
      buccal flaps is a very useful method for repairing cleft palate and possibly
      reduces postoperative complications of dehiscence, perforation, and growth
      retardation.

PMID- 14663804
TI  - Hemostatic effect of n-butyl-2-cyanoacrylate (histoacryl) glue in warfarin
      treated patients undergoing oral surgery.
AB  - PURPOSE: Our goal was to evaluate the local hemostatic effect of n-butyl-2
      cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) glue in warfarin-treated
      patients who undergo outpatient oral surgery without a change in their level of
      anticoagulation. MATERIALS AND METHODS: Thirty consecutive warfarin-treated
      patients randomly assigned to study and control groups and 10 patients who had
      never been on anticoagulant therapy serving as the negative control group were
      included in this trial. Before multiple teeth extractions, all patients had a
      prothrombin time and the international normalized ratio (INR) determined. To gain
      hemostasis and primary closure, gelatin sponge and multiple interrupted
      resorbable sutures were used in the control and negative control groups, and
      Histoacryl glue and the minimal number of interrupted resorbable sutures were
      used in the study group. Postoperatively, patients were to contact the oral
      surgeon if abnormal bleeding occurred. Patients who did not have postoperative
      bleeding were seen on the 10th postoperative day. Data were collected, and
      statistical differences in age and gender distributions, number of teeth
      extracted, INR levels, and bleeding that required treatment were analyzed with
      the Mantel-Haenzel test. Statistical significance was defined as a value of P
      <.05. RESULTS: Local hemostasis was obtained immediately in study patients and
      only after 10 to 20 minutes in the control and negative control patients. In
      relation to bleeding complications, there were no cases of postoperative bleeding
      requiring treatment in both the negative control patients and study patients. In
      the control patients, 5 cases had postoperative spontaneous bleeding that
      required treatment. This difference was statistically significant. No patient had
      wound infection and the healing process appeared to be normal. CONCLUSION:
      Multiple extractions can be performed in patients taking oral anticoagulant
      therapy without a change in their level of anticoagulation provided an efficient
      local hemostatic measure is instituted. And, in this regard, Histoacryl glue,
      used as a topical adhesive over approximated wound edges, is an effective and
      easily applicable local hemostatic for oral surgery in such patients.

PMID- 14663805
TI  - Evaluation of condylar translation by sonography versus axiography in
      orthognathic surgery patients.
AB  - PURPOSE: This study compares measurement of the condylar translation by
      sonography or axiography in preoperative assessment and follow-up of orthognathic
      surgery patients. PATIENTS AND METHODS: Forty-seven moderately dysgnathic
      patients had consecutive examinations by axiography and sonography in a blind
      fashion at a single time point by 2 observers. Thirty-nine different dysgnathic
      patients, scheduled for isolated Le Fort I osteotomy, had preoperative condylar
      translation and 24-month follow-up measured randomized by either axiography (25
      patients as control group) or sonography (14 patients as study group). RESULTS:
      The examination time for axiography was 20 minutes average versus 2 minutes for
      sonography. The mean differences were 1.7 mm in opening, 2.1 mm in protrusion,
      and 3.3 mm for mediotrusion. Pearson's proportionality quotient was r = 0.75,
      analysis of variance (P <.95, F = 3.9, alpha =.05 significance level) was not
      significant. The 24-month longitudinal follow-up showed a Pearson's
      proportionality quotient of r = 0.7 between study and control group, and no
      significant difference in analysis of variance (P <.075, F = 2.81, alpha =.05
      significance level). CONCLUSION: Sonography proved adequate for assessment and
      follow-up of condylar translation compared with axiography in orthognathic
      surgery patients. Temporomandibular joint sonography was faster and more
      comfortable, allowed 1-week postoperative examination and reexaminations, and was
      equally exact. Anatomic details like joint degeneration and disc displacement
      could be assessed. However, sonography did not measure the inclination of the
      condylar track.

PMID- 14663806
TI  - The role of midfacial degloving approach for maxillary cysts and tumors.
AB  - PURPOSE: The midfacial degloving approach has been used as a surgical approach to
      gain access to regions of the midface that would otherwise require external
      incisions. This article describes the role of this technique for various
      maxillary lesions. PATIENTS AND METHODS: Thirteen patients underwent the
      midfacial degloving technique for 8 maxillary benign lesions and 5 malignant
      lesions. This procedure uses 4 basic incisions: 1) sublabial incision, 2)
      bilateral intercartilaginous incisions, 3) septocolumellar-complete transfixion
      incisions, and 4) bilateral piriform aperture incisions extending to the
      vestibule. RESULTS: All patients successfully underwent the planned procedures
      after the midfacial degloving technique for the treatment of benign or malignant
      lesions without significant complications. Postoperative sequelae were nasal
      crusting and infraorbital hypesthesia, both of which resolved. CONCLUSIONS: The
      midfacial degloving approach offers good exposure of the mid third of the face
      with excellent cosmetic results. This approach may be combined with downfracture
      of the maxilla for access to expose and resect sinonasal malignancies. The
      midfacial degloving technique is a viable procedure with low morbidity and
      excellent cosmetic outcomes.

PMID- 14663807
TI  - Proximal segment positioning in bilateral sagittal split osteotomy:
      intraoperative controlled positioning by a positioning splint.
AB  - PURPOSE: Most techniques of proximal segment positioning hinder intraoperative
      condyle displacement. However, merely maintaining condylar position cannot
      optimize the preoperative condyle-disc-fossa relationship. This study attempts to
      optimize condylar position in the osteotomy patient. PATIENTS AND METHODS: A
      study group of 23 bimaxillary operated patients had intraoperative joint
      positioning by positioning splint and plates (9 Angle Class II, 14 Class III).
      After assessing the habitual and appraising the optimized condyle position on
      preoperative sonograms and magnetic resonance images, positioning splints were
      constructed as acrylic occlusal wafers in a semi-individual articulator. Set in
      occlusion before adaptation of positioning plates, they were intended to move the
      condyles into the calculated position. Eighteen bimaxillary operated control
      patients had conventional plate positioning according to the habitual occlusion
      (9 Angle Class II, 9 Class III). Clinical follow-up, axiography, or sonography
      was maintained for 24 months. Preoperative lateral cephalograms were scrutinized
      for horizontal and vertical joint spaces and compared with the immediate
      postoperative radiography. RESULTS: Postoperative Class II study group patients
      had less dorsal and more vertical joint space and Class III patients more dorsal
      and vertical space compared with the controls. The study group exhibited
      significantly less postoperative dysfunction compared with the control group (2
      way analysis of variance: P <.021, F = 9.2, alpha =.05 significance level), disc
      dislocation prevalence was lower (P <.07, F = 9.2), postoperative changes in
      condylar translation were smaller (P <.014, F = 4.9), and 8% skeletal relapses
      versus 22% in the controls were seen. CONCLUSIONS: A proximal segment-positioning
      splint effectively positioned the condyle in the desired direction, but with
      considerable relapse, significantly reduced postoperative dysfunction, disc
      dislocations, changes to the condylar translation, and incidence of skeletal
      relapse at 24-month follow-up.

PMID- 14663808
TI  - Tranexamic acid mouthwash versus autologous fibrin glue in patients taking
      warfarin undergoing dental extractions: a randomized prospective clinical study.
AB  - PURPOSE: The aim of this prospective study was to compare the effectiveness of a
      4.8% tranexamic acid mouthwash versus an autologous fibrin glue preparation to
      control hemostasis in patients therapeutically anticoagulated with warfarin who
      required dental extractions without interruption of their treatment. PATIENTS AND
      METHODS: The 49 patients who underwent 152 dental extractions were randomly
      allocated to 2 groups: Group A were required to rinse with 10 mL of a 4.8%
      tranexamic acid solution 4 times a day for 7 days postoperatively. Group B
      received autologous fibrin glue intraoperatively. The international normalized
      ratio was measured on the day of the procedure. All procedures were performed on
      an ambulatory basis by the same surgeon. RESULTS: Of the 49 patients, 2 presented
      with postoperative bleeding (4%). Both patients were from the autologous fibrin
      glue group and were found to have grossly elevated international normalized
      ratios on the day of the bleeding that was unaccounted for. CONCLUSIONS: This
      study supports the consensus that dental extractions can be performed without
      modification of oral anticoagulant treatment. Local hemostasis with an absorbable
      oxidized cellulose mesh, tranexamic acid, and sutures is the more cost efficient
      of the 2 methods compared; however, autologous fibrin glue has an important role
      in patients unable to use a mouthwash effectively.

PMID- 14663809
TI  - Risk factors associated with prolonged recovery and delayed healing after third
      molar surgery.
AB  - PURPOSE: We sought to identify the demographic, oral health, and surgical risk
      factors associated with prolonged recovery after third molar surgery using health
      related quality of life (HRQOL) and clinical outcomes. PATIENTS AND METHODS:
      HRQOL responses from patients and clinical outcomes were obtained after third
      molar surgery. Criteria were selected for HRQOL outcomes that separated patients
      with from those without prolonged recovery. Delayed clinical healing was
      indicated by a patient having at least 1 postsurgery visit with treatment. Risk
      assessment models for prolonged HRQOL recovery and delayed clinical healing were
      developed using stepwise logistic regression analysis. RESULTS: We included 547
      subjects with HRQOL and clinical outcome data in this analysis. Age, gender, and
      occlusal plane position were statistically significantly associated with
      prolonged recovery for early symptoms, oral function, and pain. Recovery for
      lifestyle was prolonged only if both lower third molars were below the occlusal
      plane before surgery. Age, gender, prior symptoms related to the third molars,
      and the surgeon's perception of difficulty were statistically significant
      predictors of delayed clinical recovery. CONCLUSIONS: Certain demographic and
      oral health conditions available to the surgeon before surgery, and
      characteristics of the surgery itself, increase the risk of a prolonged recovery
      for HRQOL outcomes and delayed clinical outcomes after third molar surgery.

PMID- 14663810
TI  - Transforming growth factor-alpha and oral fibroma: Immunohistochemical and in
      situ hybridization study.
AB  - PURPOSE: Transforming growth factor-alpha (TGF-alpha) is usually expressed in
      cell lines derived from sarcomas. It is known as a mitogen for fibroblasts. The
      aim of this study was to determine whether there were any differences in the
      expression pattern of TGF-alpha between normal oral mucosa and oral fibroma.
      PATIENTS AND METHODS: Fourteen pathologic specimens (6 males and 8 females; 37.2
      +/- 23.2 years) and 10 normal oral mucosal specimens (5 females and 5 males; 43.8
      +/- 17.7 years) were used for this study. Identification of TGF-alpha was sought
      by using immunohistochemistry and in situ hybridization. RESULTS: The samples
      from normal oral mucosa did not express TGF-alpha. One sample from oral fibroma
      did not express TGF-alpha (7.1%). Five samples from oral fibroma expressed TGF
      alpha sparsely (35.7%). Eight samples showed diffuse expression of TGF-alpha
      (57.1%). The immunopositive reaction to TGF-alpha in oral fibroma was localized
      in the basal layer and the fibroblasts that resided beneath the epithelium. This
      pattern was also shown in the in situ hybridization study as well. CONCLUSION:
      TGF-alpha is expressed in oral fibromas. It suggested that TGF-alpha might play a
      role in fibroblast proliferation in oral fibromas.

PMID- 14663811
TI  - Bone tissue engineering by primary osteoblast-like cells in a monolayer system
      and 3-dimensional collagen gel.
AB  - PURPOSE: To engineer living bone tissue in vitro, bone cells must be multiplied
      and differentiated in cell culture. Osteoblasts are known to be the crucial cells
      responsible for the bone modeling process. Periosteal-derived osteoblasts were
      therefore cultured for up to 3 weeks in Petri dishes as well as in a 3
      dimensional collagen gel. METHODS: Proliferation, migration, and differentiation
      of cells as well as the synthesis of extracellular matrix proteins were monitored
      during the culture period by histology, electron microscopy, and
      immunohistochemistry. Mineral formation was investigated by electron diffraction
      studies and element analysis. RESULTS: Osteoblasts proliferated and migrated in
      Petri dishes as well as in the collagen gel without loss of viability during the
      whole experimental period. They demonstrated a mature osteoblast phenotype as
      indicated by the synthesis of a bone-like extracellular matrix. They formed an
      extracellular matrix containing osteocalcin, osteonectin, and newly synthesized
      collagen type I in both environments. Mineral formation was seen in
      colocalization with the bone-like extracellular matrix proteins in Petri dishes.
      Microanalytical investigations revealed a matrix vesicle-mediated mineral
      formation at early stages of culture. CONCLUSIONS: Our cell culture confirmed the
      ability to multiplicate differentiated and viable osteoblast-like cells in 2- and
      3-dimensional space. Additionally, bone-like mineralization can be induced by
      primary osteoblasts in monolayer culture. The data suggest that this approach can
      be used as a tool in bone tissue engineering.

PMID- 14663812
TI  - The expression of apoptotic proteins and matrix metalloproteinases in odontogenic
      myxomas.
AB  - PURPOSE: The odontogenic myxoma is a rare benign tumor affecting the jaws. We
      hypothesize that odontogenic myxomas have dysregulated antiapoptotic mechanisms
      to assist in neoplastic growth. We believe that antiapoptotic proteins of the Bcl
      2 family are over expressed and that tumor cells must generate some form of
      matrix proteinase. The aim of this study was to evaluate odontogenic myxomas for
      the expression of cell cycle protein Ki-67, apoptosis-regulating proteins Bcl-2,
      Bcl-XL, Bak, and Bax, and matrix metalloproteinases MMP-2, MMP-3, and MMP-9.
      MATERIALS AND METHODS: Odontogenic myxomas submitted to oral pathology between
      1974 and 1998 were evaluated. Twenty-six paraffin-embedded tissue sections were
      used in a standard immunohistochemistry protocol and incubated with one of the
      following antibodies: Bcl-2, Bcl-XL, Bak, Bax, or Ki-67. The sections were then
      incubated with anti-immunoglobulin conjugated to peroxidase-labeled dextran
      polymer in a Tris-HCl buffer. Counts of positive (staining) cells were completed
      in 5 high-power fields for each specimen. Each slide was reviewed by 2
      investigators, and final data were pooled and averaged. RESULTS: Specimen slides
      showed an increase in cells staining positively for anti-apoptotic proteins Bcl-2
      and Bcl-X. An average of 6.5% of specimen cells were positive for Bcl-2 and 10.4%
      for Bcl-X. Control tissue showed only 1.1% of cells to be positive for Bcl-2 and
      1.2% for Bcl-X. Less than 1% of both specimen and control cells stained
      positively for Ki-67. Proapoptotic proteins (Bak and Bax) were not detected in
      tumor cells. Ninety percent of tumor cells stained positively for MMP-2 compared
      with 10% of controls. Specimen and controls were negative for MMP-3 and MMP-9.
      CONCLUSION: Odontogenic myxoma tumor cells did not show an increase in cell
      division. Less than 1% of tumor and control cells were positive for Ki-67.
      Odontogenic myxoma tumor cells showed increased expression of antiapoptotic
      proteins (Bcl-2 and Bcl-X) and the matrix metalloproteinase MMP-2. This study
      suggests that 2 mechanisms of disease progression used by the odontogenic myxoma
      are the production of antiapoptotic proteins and the secretion of matrix
      metalloproteinases.

PMID- 14663813
TI  - The effects of articaine hydrochloride on wound healing: an experimental study.
AB  - PURPOSE: The aim of the study was to examine the effect of articaine
      hydrochloride (AH) on the healing of surgical wounds and to compare healing with
      that of lidocaine. MATERIALS AND METHODS: Forty rats were used in this study. The
      rats were randomly separated into 4 groups. Three groups were given 2% lidocaine,
      4% AH, or injectable saline, and the fourth was a control group. Skin specimens
      underwent the breaking strength test (BST) and histologic examination at 1 week
      after the surgical procedure. The skin specimens of the rats were subjected to a
      pulling force of 10 mm/min across the incision line. The strength value at the
      moment of breaking in the tissue was expressed in Newtons. Histologic examination
      was performed as well, and wound healing was graded. RESULTS: Both the histologic
      grade and BST values in the lidocaine and AH groups were significantly lower than
      those of the control and saline groups (P <.01). Similarly, the histologic and
      BST values of the AH and lidocaine groups were statistically significant (P <.05,
      P <.001). Some necrotic regions were observed at the incision region in 2 samples
      from the AH group. CONCLUSION: The results of the study showed that AH is as safe
      a local anesthetic agent as lidocaine from the standpoint of wound response.

PMID- 14663814
TI  - The fixation of sagittal split osteotomies with miniplates: the versatility of a
      technique.

PMID- 14663815
TI  - Bicortical screw stabilization of sagittal split osteotomies.

PMID- 14663816
TI  - Salivary duct fistula and recurrent buccal space infection: a complication of
      Crohn's disease.

PMID- 14663817
TI  - Variations in clinical presentations of the simple bone cyst: report of cases.

PMID- 14663818
TI  - Hodgkin's lymphoma: a case report involving the mandible.

PMID- 14663819
TI  - Posterior iliac crest bone harvest: review of technique, complications, and use
      of an epidural catheter for postoperative pain control.

PMID- 14663824
TI  - Purification, characterization and functional cloning of inositol oxygenase from
      Cryptococcus.
AB  - The enzyme inositol oxygenase (myo-inositol : oxygen oxidoreductase; E.C.
      1.13.99.1) is a monooxygenase that converts inositol into glucuronic acid in the
      presence of molecular oxygen. This enzyme is integrated into a pathway leading to
      either degradation and energy production or the biosynthesis of precursors for
      polysaccharides. The enzyme was purified from the yeast Cryptococcus lactativorus
      by a five-step chromatography procedure. The purified enzyme shows a molecular
      mass of 37 kDa on SDS-PAGE, similar to the estimation of the size of the native
      enzyme determined by size exclusion chromatography. Peptides of the inositol
      oxygenase protein derived from a tryptic digest were sequenced de novo by
      nanoelectrospray tandem mass spectrometry. Using degenerate oligonucleotides, the
      corresponding gene was cloned from first strand cDNA. The open reading frame
      encodes a 315 amino acid polypeptide with a predicted molecular mass of 36.9 kDa.
      Inositol oxygenase is a single copy gene in C. lactativorus. It has close
      homologues in other fungi such as Cryptococcus neoformans and Neurospora crassa.
      Biochemical characterization of the enzyme showed a pH optimum of 6-6.5 and a
      temperature optimum of 30 degrees C. Myo-inositol is the only accepted substrate
      with a Km of ca. 5 mM. The enzyme contains a Fe-centre but the enzyme activity is
      resistant to KCN.

PMID- 14663825
TI  - Cloning and sequence analysis of the TRP1 gene encoding the phosphoribosyl
      anthranilate isomerase from Pichia anomala (strain K).
AB  - Pichia anomala (strain K) is an efficient biocontrol agent against post-harvest
      diseases affecting apples. To study the role of strain K genes in biocontrol
      activity, it is useful to identify selectable markers on which to base a gene
      disruption strategy. The Pichia anomala TRP1 gene (PaTRP1) was isolated by
      complementation of the multi-auxotrophic S. cerevisiae strain FY-1679-18b. DNA
      sequence analysis revealed the presence of a 699 bp ORF encoding a 233 amino acid
      protein showing the typical conserved structure of proteins of the phosphoribosyl
      anthranilate isomerase (PRAI) family. Codon analysis revealed a high number of
      unused codons. Downstream from PaTRP1 was found the 3' extremity of a gene highly
      similar to the IPP1 gene (coding for the inorganic pyrophosphatase).

PMID- 14663826
TI  - New modules for PCR-based gene targeting in Candida albicans: rapid and efficient
      gene targeting using 100 bp of flanking homology region.
AB  - The use of PCR-based techniques for directed gene alterations has become a
      standard tool in Saccharomyces cerevisiae. In our efforts to increase the speed
      of functional analysis of Candida albicans genes, we constructed a modular system
      of plasmid vectors and successfully applied PCR-amplified functional analysis
      (FA)-cassettes in the transformation of C. albicans. These cassettes facilitate:
      (a) gene disruptions; (b) tagging of 3'-ends of genes with green fluorescent
      protein (GFP); and (c) replacements of endogenous promoters to achieve regulated
      expression. The modules consists of a core of three selectable marker genes,
      CaURA3, CaHIS1 and CaARG4. Modules for C-terminal GFP-tagging were generated by
      adding GFP-sequences flanked at the 5'-end by a (Gly-Ala)3-linker and at the 3'
      end by the S. cerevisiae URA3-terminator to these selection markers. Promoter
      exchange modules consist of the respective marker genes followed by the
      regulatable CaMAL2 or CaMET3 promoters at their 3'-ends. In order to ensure a
      reliably high rate of homologous gene targeting, the flanking homology regions
      required a size of 100 bp of gene-specific sequences, which were provided with
      the oligonucleotide primers. The use of shorter flanking homology regions
      produced unsatisfactory results with C. albicans strain BWP17. With these new
      modules only a minimal set of primers is required to achieve the functional
      analysis of C. albicans genes and, therefore, provides a basic tool to increase
      the number of functionally characterized C. albicans genes of this human pathogen
      in the near future.

PMID- 14663827
TI  - Role of Tea1p, Tea3p and Pom1p in the determination of cell ends in
      Schizosaccharomyces pombe.
AB  - Schizosaccharomyces pombe cells are rod-shaped and grow along a single axis from
      their two ends. Microtubules extend from the cell centre terminating at the cell
      ends. The ERM(ezrin/radixin/moesin)-like proteins Tea1p and Tea3p, and the Dyrk
      like kinase Pom1p are cell end markers involved in the regulation of growth and
      microtubular dynamics at the cell ends. We have analysed the relative
      contribution of these three proteins to the determination of cell ends as sites
      both for cell growth and for microtubular termination. Pom1Delta, in combination
      with Tea1Delta or Tea3Delta, has the greatest difficulty in relocalizing actin to
      the cell ends following actin depolymerization and generates the most defective
      growth pattern. Tea1Delta, in combination with Pom1Delta or Tea3Delta, displays
      the highest number of microtubules bending round the cell ends.
      Tea1DeltaPom1Delta, which has the most defective growth pattern and microtubules,
      also displays the highest number of branched cells. We show that Tea1p, Tea3p and
      Pom1p all contribute, to different extents, to the determination of cell ends, as
      sites for both cell growth and microtubular termination. We also show that the
      fission yeast cell relies on both the positioning of landmarks and a properly
      organized microtubule cytoskeleton to direct cell growth.

PMID- 14663828
TI  - A DNA region of Torulaspora delbrueckii containing the HIS3 gene: sequence, gene
      order and evolution.
AB  - We cloned a genomic DNA fragment of the yeast Torulaspora delbrueckii by
      complementation of a Saccharomyces cerevisiae his3 mutant strain. DNA sequence
      analysis revealed that the fragment contained two complete ORFs, which share a
      high similarity with S. cerevisiae His3p and Mrp51p, respectively. The cloned
      TdHIS3 gene fully complemented the his3 mutation of S. cerevisiae, confirming
      that it encodes for the imidazoleglycerol-phosphate dehydrate of T. delbrueckii.
      Two additional ORFs, with a high homology to S. cerevisiae PET56 and DED1 genes,
      were mapped upstream and downstream from TdHIS3 and TdMRP51, respectively. This
      genetic organization is analogous to that previously found in Saccharomyces
      kluyveri and Zygosaccharomyces rouxii. The evolutionary significance of gene
      order in this chromosomal region is analysed and discussed.

PMID- 14663829
TI  - Genome-wide monitoring of wine yeast gene expression during alcoholic
      fermentation.
AB  - The transcriptome of a wine yeast was monitored throughout an alcoholic
      fermentation under conditions mimicking an enological environment. Major changes
      in gene expression occurred during fermentation, affecting more than 2000 genes,
      as the yeast adapted to changing nutritional, environmental and physiological
      conditions. The genes of many pathways are regulated in a highly coordinated
      manner, and genes involved in the key metabolic pathways of fermentation are
      strongly expressed. We showed that, during fermentation of a synthetic medium
      mimicking a natural must in which growth arrest was caused by nitrogen
      exhaustion, entry into the stationary phase triggered major transcriptional
      reprogramming. Many TOR target genes involved in nitrogen utilization or other
      functions are induced at this stage, suggesting that this signalling pathway
      plays a critical role in changes in gene expression in response to nitrogen
      depletion. Entry into stationary phase is a key physiological event and is
      followed by a general stress response. The superimposition of multiple stresses,
      including starvation and ethanol stress, gives rise to a unique stress response,
      involving hundreds of genes encoding proteins involved in various cellular
      processes, many of unknown function.

PMID- 14663830
TI  - Molecular and cytogenetic characterization of extra-structurally abnormal
      chromosomes (ESACs) found prenatally: outcome and follow-up.
AB  - A 40-year-old woman underwent amniocentesis at 15.3 weeks of gestation.
      Chromosome analysis performed using QFQ, DA-DAPI and CBG banding revealed two de
      novo extra-chromosomal markers (ESACs) in 11 of the 16 colonies analysed.
      Fluorescence in situ hybridization (FISH) showed that both chromosomes came from
      the Yq11.22.1 region of the Y chromosome. PCR analysis of genes and STS localized
      on the Y chromosome excluded the Yp presence specifically of the SRY gene, and
      most of the euchromatic region of Yq. After extensive genetic counselling and
      considering both laboratory and second-level ultrasound data, the couple decided
      to continue the pregnancy. At 37.4 weeks of gestational age, a girl weighing 2750
      g was born with an Apgar score of 9/10. A blood sample taken from the umbilical
      cord showed three cellular lines: mos47,XX, +mar1 ish.der (Y)(wcpY+) [21%]/48,XX,
      +mar1 ish.der (Y)(wcpY+), +mar2 ish.der (Y)(wcpY+) [41%]/46,XX [38%]. One year
      after birth, the baby was developing normally and had normal psychomotorial
      activity.

PMID- 14663831
TI  - Transcervical fetoscopic diagnosis of structural defects in four first-trimester
      monochorionic twin intrauterine deaths.
AB  - OBJECTIVE: While chromosomal abnormalities are often the cause of early failed
      pregnancies, other mechanisms could be involved in monochorionic twin
      intrauterine deaths, that might be screened for careful morphological analysis.
      METHODS: Transcervical fetoscopy prior to instrumental evacuation of the uterus
      was performed in four first-trimester monochorionic twin intrauterine deaths.
      RESULTS: We present fetoscopic and cytogenetic findings in four cases of
      monochorionic twin intrauterine deaths. In the first, generalized abnormal
      embryonic development observed in both twins was a manifestation of trisomy 20.
      The second (thoracophagus) and third (acardius) pair of twins had anomalies
      peculiar to multiple gestations. The fourth pair of twins was remarkable because
      of the concordance for the observed limb-reduction defects. CONCLUSION:
      Malformations of first-trimester monochorionic twin intrauterine deaths might
      cover a wide spectrum of etiologies from abnormal chromosomes and single gene
      defects to rare duplication anomalies. Their detection by careful morphological
      analysis and the identification of a specific mechanism provides valuable
      information for genetic counseling and prenatal investigation in a future
      pregnancy.

PMID- 14663832
TI  - Prenatal imaging of facial clefts by magnetic resonance imaging with emphasis on
      the posterior palate.
AB  - OBJECTIVE: To evaluate the role of Magnetic Resonance Imaging (MRI) in the
      prenatal diagnosis of facial clefts. MATERIALS AND METHODS: Six fetuses with a
      sonographic diagnosis of cleft lip and palate underwent MRI at a median age of 30
      weeks (range 28-32). The defect was bilateral in two cases. RESULTS: Fetal MRI
      confirmed the presence of a cleft involving at least the anterior palate in all
      cases. Distinction between unilateral and bilateral clefts could be made in all
      cases and was always confirmed after birth. Sagittal views of the fetal face were
      found to be particularly useful in identifying the degree of extension of the
      cleft into the palate. The diagnosis was confirmed after birth. CONCLUSION: Our
      results suggest that MRI may be ancillary to ultrasound in prenatal investigation
      of a fetus with cleft lip, allowing a better staging of the lesion by
      demonstrating the degree of involvement of the palate.

PMID- 14663833
TI  - Chorioangioma and its severe infantile sequelae: case report.
AB  - OBJECTIVE: This case report describes a rare clinical presentation of
      chorioangioma diagnosed prenatally because of raised-maternal serum (MS) alpha
      fetoprotein. METHODS: A thirty-year-old woman gravida 2, para 1 was referred to
      the ultrasound unit at 18 weeks of gestation because of abnormal MS triple-test
      results. This included AFP level of 14.9 MoM; hCG of 3.42 MoM and uE3 of 1.01
      MoM. A detailed anomaly scan revealed a singleton fetus with no sonographically
      detectable malformations and normal amniotic fluid. The placenta was posterior. A
      well-circumscribed, rounded, predominantly hypoechoic lesion near the chorionic
      surface measuring 5 x 5 cm and protruding into the amniotic cavity was detected.
      Color Doppler sonogram showed no blood flow within the mass, but clear fetal
      waveforms in its periphery were demonstrated, and the diagnosis of chorioangioma
      was made. The pregnancy was followed uneventfully until 35 weeks of gestation
      when polyhydramnios and severe fetal cardiomegaly developed. Labor was therefore
      induced. RESULTS: A euploid female, who had multiple diffuse cutaneous and liver
      angiomatosis was born. She died at the age of one month because of cardiac
      failure and infection. CONCLUSIONS: The present case alerts to the
      interrelationship between placental and fetal angiomas. This may lead to severe
      infantile sequelae because of similar lesions.

PMID- 14663834
TI  - Prenatal diagnosis of sacrococcygeal teratoma with constitutional partial
      monosomy 7q/trisomy 2p.
AB  - We report the prenatal diagnosis of a fetus with sacrococcygeal teratoma and
      facial dysmorphism attributed to a constitutional terminal deletion of chromosome
      7q and partial trisomy of chromosome 2p likely resulting from a de novo balanced
      translocation. The cytogenetic abnormality was diagnosed prenatally after
      sonographic detection of teratoma and confirmed on peripheral blood cells at
      birth. The newborn died of post-operative complications at seven days of age.
      FISH analysis demonstrated haploinsufficiency of HLXB9, a gene identified in the
      triad of a presacral mass (teratoma or anterior meningocele), sacral agenesis,
      and anorectal malformation, which constitutes the Currarino syndrome. Despite the
      absence of other features of the triad, the teratoma observed in the fetus we
      describe might represent a partial form of Currarino syndrome.

PMID- 14663835
TI  - Increased nuchal translucency and congenital heart defects in a low-risk
      population.
AB  - OBJECTIVE: Increased first-trimester nuchal translucency (NT) is a possible
      marker for congenital heart defects in euploid fetuses. In this study, we wanted
      to determine the sensitivity for congenital heart defects using the 95th centile
      of the NT as a cut-off point. METHODS: All women who booked for delivery in our
      hospital in the first trimester underwent NT measurement at a crown-rump length
      (CRL) of between 35 and 75 mm. In all euploid fetuses and newborns with isolated
      or associated CHD, NT was examined retrospectively and classified as normal
      (<95th centile according to CRL-dependent centiles in our own data) or increased
      (> or =95th centile). RESULTS: From a total of 12,978 euploid fetuses screened,
      27 had CHD (22 isolated and 5 cases associated with additional malformations).
      Moreover, 7 of the 27 fetuses also had increased NT (26%). Increased NT was
      significantly more frequent in fetuses with associated CHD (4/5) than in those
      with isolated CHD (3/22, Yates corrected chi2 p=0.012). In fact, the relative
      risk for CHD was 6.6 times higher in fetuses with increased NT compared to those
      with normal NT. CONCLUSION: Increased NT for the detection of CHD performed less
      well than in other studies. Nevertheless, it can be used as an indication for
      fetal echocardiography.

PMID- 14663836
TI  - Predicting complications of pregnancy with first-trimester maternal serum free
      betahCG, PAPP-A and inhibin-A.
AB  - OBJECTIVE: To find whether fbetahCG, PAPP-A and inhibin-A levels in maternal
      serum or fetal nuchal translucency (NT) thickness at the first-trimester
      screening for trisomy 21 (T21) might detect women at high risk for adverse
      pregnancy outcomes. METHODS: A retrospective analysis of 1136 women with
      singleton pregnancy between 10 and 14 weeks. Women with pregnancy complications
      were allotted to five subgroups: small for gestational age (SGA), large for
      gestational age (LGA), gestational diabetes (GDM), hypertensive disorders,
      preterm delivery; women with normal pregnancy represented the control group. NT,
      maternal serum fbetahCG, PAPP-A and inhibin-A were measured. Mann-Whitney test
      was used for the comparison of fbetahCG, PAPP-A, inhibin-A and NT between a
      subgroup of a certain pregnancy complication and the control group. Multivariate
      logistic regression models were built to explore the relationship among different
      variables and the occurrence of pregnancy complications. RESULTS: PAPP-A values
      were significantly lower in women who delivered SGA babies (n=51, 0.76 MoM;
      p=0.002) and significantly higher in women who delivered LGA babies (n=120, 1.12
      MoM; p=0.036). In women with GDM (n=27), fbetahCG, PAPP-A and inhibin-A were
      insignificantly lower than in controls, whereas in women with hypertensive
      disorders (n=56) no significant differences between the groups were found. In
      women with a preterm delivery (<34 weeks) (n=17), inhibin-A levels were
      significantly higher (1.25 MoM; p=0.015). CONCLUSION: Low PAPP-A level is
      associated with the delivery of an SGA baby and high PAPP-A with the delivery of
      an LGA baby. High inhibin-A is associated with preterm delivery before 34 weeks.
      Feto-placental products in the first trimester do not prove to be useful as a
      screening tool for predicting pregnancy complications.

PMID- 14663837
TI  - Congenital cystic adenomatoid malformation: accuracy of prenatal diagnosis,
      prevalence and outcome in a general population.
AB  - OBJECTIVES: Most available data regarding accuracy of prenatal diagnosis,
      prevalence and outcome of congenital cystic adenomatoid malformation (CCAM) are
      derived largely from tertiary referral centres and may not reflect general
      population rates. We aimed to describe the accuracy of prenatal diagnosis,
      ascertain the population prevalence and post-natal outcome for cases of suspected
      CCAM. METHODS: Retrospective collection of prenatal and paediatric data for cases
      of suspected CCAM notified to the Trent Congenital Anomalies Register 1997 to
      2001. RESULTS: Thirty-seven cases of CCAM were suspected prenatally. Twenty-one
      cases were confirmed post-natally as having a CCAM (positive predictive value
      57%). Eighteen of the 21 cases were delivered at term as live births, 15 of which
      have undergone successful surgery to date. Thirteen of the 37 cases had
      apparently resolved by delivery. Three further cases were subsequently found to
      be cases of lung sequestration or lobar emphysema. Five cases of CCAM were
      detected after delivery (sensitivity of prenatal detection 81%). The population
      prevalence at delivery was 9.0 per 1,00,000 total births. Five confirmed cases of
      CCAM developed hydrops, three required in utero intervention and delivered as
      live births at term, one was terminated and one died in utero. The overall
      mortality in the confirmed cases of CCAM was 23% of which the majority were
      terminations of pregnancy. CONCLUSIONS: Problems of diagnostic accuracy and
      apparent resolution of CCAM render counselling difficult, although our data
      suggest that the prognosis is better than others have reported. Confirmation of
      the diagnosis in the neonatal period is vital in order to obtain the true
      population prevalence figures and to interpret outcome data.

PMID- 14663838
TI  - Living with achondroplasia: attitudes toward population screening and correlation
      with quality of life.
AB  - OBJECTIVES: Since the discovery of the gene that causes achondroplasia,
      population-wide prenatal screening for this condition has become a possibility.
      This study sought to assess attitudes toward screening for achondroplasia and
      correlation with quality of life in a population of individuals affected with
      achondroplasia and first-degree relatives. METHODS: Surveys were collected from
      189 individuals affected with achondroplasia and 136 average-statured first
      degree relatives. RESULTS: While 87% of all respondents would support the use of
      prenatal screening by affected parents at risk of having a fetus with the
      homozygous, lethal form of achondroplasia, 29% would support general population
      prenatal screening for achondroplasia. Attitudes supporting general population
      screening were more likely to be held by those people with less education, who
      were affected with achondroplasia, who supported abortion, and who believed that
      achondroplasia is a serious condition without any accompanying advantages
      (p<0.01). Those respondents who felt positively toward offering the prenatal test
      for individuals at risk for homozygous achondroplasia were more likely to have
      lower mean quality of life scores and to support abortion in general (p<0.05).
      CONCLUSION: These data suggest that opinions about prenatal screening are
      heterogeneous within this study population and are related to individuals'
      experiences and perceptions of the condition. Future research is needed to assess
      attitudes toward population screening and quality of life in communities of
      individuals affected with genetic conditions, both to support policy decisions
      and to inform the education and counseling provided in the prenatal setting.

PMID- 14663839
TI  - Prenatal diagnosis of Apert syndrome: report of two cases.
AB  - Two de novo cases with Apert Syndrome detected prenatally are presented herein.
      In the first, fetal ultrasound findings of syndactyly of the hands,
      craniosynostosis and proptosis resulted in a prenatal diagnosis in the nineteenth
      week of gestation. This is the earliest prenatal diagnosis of this syndrome in a
      not-at-risk case. Following counseling, this pregnancy was terminated and
      subsequent pathological examination and DNA analysis confirmed the diagnosis of
      Apert Syndrome and coarctation of the aorta. In the second case, fetal ultrasound
      at 21 weeks' gestation revealed a hypoplastic left heart and clover-leaf skull.
      Following counseling, this pregnancy was also terminated. Further examination of
      the fetus and DNA analysis led to a diagnosis of Apert Syndrome. These cases
      emphasize the need to complete a thorough fetal ultrasound in cases with
      potentially lethal cardiac abnormality and the importance of incorporating a
      fetal pathologist, as well as a medical geneticist, in the investigations
      performed after delivery or pregnancy termination when a fetal abnormality is
      detected on ultrasound.

PMID- 14663840
TI  - Prenatal diagnosis and genetic analysis of Wiskott-Aldrich syndrome.

PMID- 14663841
TI  - CGH analysis in a cohort of 17 chromosomally normal fetuses with an increased
      nuchal translucency.

PMID- 14663842
TI  - Fetoplacental and fetoamniotic chromosomal discrepancies in prenatally detected
      mosaic trisomy 9.

PMID- 14663843
TI  - Mosaic trisomy 13 on chorionic villi in a fetus with body wall complex:
      fortuitous association or pathogenic hypothesis?

PMID- 14663844
TI  - Analysis of CFTR mutation screening in cases of isolated fetal echogenic bowel in
      the South Australian population.

PMID- 14663845
TI  - Performance analysis of an iSCSI-based unified storage network.
AB  - In this paper, we introduced a novel storage architecture "Unified Storage
      Network", which merges NAC(Network Attached Channel) and SAN(Storage Area
      Network), and provides the file I/O services as NAS devices and provides the
      block I/O services as SAN. To overcome the drawbacks from FC, we employ iSCSI to
      implement the USN(Unified Storage Network). To evaluate whether iSCSI is more
      suitable for implementing the USN, we analyze iSCSI protocol and compare it with
      FC protocol from several components of a network protocol which impact the
      performance of the network. From the analysis and comparison, we can conclude
      that the iSCSI is more suitable for implementing the storage network than the FC
      under condition of the wide-area network. At last, we designed two groups of
      experiments carefully.

PMID- 14663846
TI  - An efficient algorithm for mining closed itemsets.
AB  - This paper presents a new efficient algorithm for mining frequent closed
      itemsets. It enumerates the closed set of frequent itemsets by using a novel
      compound frequent itemset tree that facilitates fast growth and efficient pruning
      of search space. It also employs a hybrid approach that adapts search strategies,
      representations of projected transaction subsets, and projecting methods to the
      characteristics of the dataset. Efficient local pruning, global subsumption
      checking, and fast hashing methods are detailed in this paper. The principle that
      balances the overhead of search space growth and pruning is also discussed.
      Extensive experimental evaluations on real world and artificial datasets showed
      that our algorithm outperforms CHARM by a factor of five and is one to three
      orders of magnitude more efficient than CLOSET and MAFIA.

PMID- 14663847
TI  - Super-proximity routing in structured peer-to-peer overlay networks.
AB  - Peer-to-Peer systems are emerging as one of the most popular Internet
      applications. Structured Peer-to-Peer overlay networks use identifier based
      routing algorithms to allow robustness, load balancing, and distributed lookup
      needed in this environment. However, identifier based routing that is independent
      of Internet topology tends to be of low efficiency. Aimed at improving the
      routing efficiency, the super-proximity routing algorithms presented in this
      paper combine Internet topology and overlay routing table in choosing the next
      hop. Experimental results showed that the algorithms greatly improve the
      efficiency of Peer-to-Peer routing.

PMID- 14663848
TI  - A hierarchical architecture of centralized monitoring and controlling system and
      its high-performance and interoperability protocol.
AB  - This paper describes a hierarchical architecture and a high-performance and
      interoperability protocol for centralized monitoring and controlling systems
      (CMCS). The protocol we proposed can interoperate different monitoring and
      controlling systems constructed by different companies, each with different
      functions and communication protocols. The protocol reduces the amount of traffic
      and has real-time and high-performance advantages. The protocol was implemented
      in CMCS for telecommunication power supply and air-conditioner used by the
      Telecommunication Bureau of Zhejiang Province. This paper deals with the
      hierarchical architecture and function of CMCS and packet format, command ID, and
      SDL description of its protocol. We also discuss the properties of the
      interoperability and performance of the protocol in this paper.

PMID- 14663849
TI  - Using multi-class queuing network to solve performance models of e-business
      sites.
AB  - Due to e-business's variety of customers with different navigational patterns and
      demands, multi-class queuing network is a natural performance model for it. The
      open multi-class queuing network(QN) models are based on the assumption that no
      service center is saturated as a result of the combined loads of all the classes.
      Several formulas are used to calculate performance measures, including
      throughput, residence time, queue length, response time and the average number of
      requests. The solution technique of closed multi-class QN models is an
      approximate mean value analysis algorithm (MVA) based on three key equations,
      because the exact algorithm needs huge time and space requirement. As mixed multi
      class QN models, include some open and some closed classes, the open classes
      should be eliminated to create a closed multi-class QN so that the closed model
      algorithm can be applied. Some corresponding examples are given to show how to
      apply the algorithms mentioned in this article. These examples indicate that
      multi-class QN is a reasonably accurate model of e-business and can be solved
      efficiently.

PMID- 14663850
TI  - Untraceable partially blind signature based on DLOG problem.
AB  - This paper proposes a new untraceable Partially Blind Signature scheme which is a
      cross between the traditional signature scheme and the blind signature scheme. In
      this proposed scheme, the message M that the signer signed can be divided into
      two parts. The first part can be known to the signer (like that in the
      traditional signature scheme) while the other part cannot be known to the signer
      (like that in the blind signature scheme). After having signed M, the signer
      cannot determine if he has made the signature of M except through the part that
      he knows. We draw ideas from Brands' "Restricted Blind Signature" to solve the
      Untraceable Partially Blind Signature problem. Our scheme is a probabilistic
      signature scheme and the security of our Untraceable Partially Blind Signature
      scheme relies on the difficulty of computing discrete logarithm.

PMID- 14663851
TI  - A simple channel estimator for space-time coded OFDM systems in rapid fading
      channels.
AB  - A simple channel estimator for space-time coded orthogonal frequency division
      multiplexing (OFDM) systems in rapid fading channels is proposed. The channels at
      the training bauds are estimated using the EM (expectation-maximization)
      algorithm, while the channels at the data bauds are estimated based on the method
      for modelling the time-varying channel as the linear combination of several time
      invariant "Doppler channels". Computer simulations showed that this estimator
      outperforms the decision-directed tracking in rapid fading channels and that the
      performance of this method can be improved by iteration.

PMID- 14663852
TI  - Verifiable threshold signature schemes against conspiracy attack.
AB  - In this study, the author has designed new verifiable (t,n) threshold untraceable
      signature schemes. The proposed schemes have the following properties:(1)
      Verification: The shadows of the secret distributed by the trusted center can be
      verified by all of the participants;(2) Security: Even if the number of the
      dishonest member is over the value of the threshold, they cannot get the system
      secret parameters, such as the group secret key, and forge other member's
      individual signature;(3) Efficient verification: The verifier can verify the
      group signature easily and the verification time of the group signature is
      equivalent to that of an individual signature; (4) Untraceability: The signers of
      the group signature cannot be traced.

PMID- 14663853
TI  - Multiple descriptions based wavelet image coding.
AB  - We present a simple and efficient scheme that combines multiple descriptions
      coding with wavelet transform under JPEG2000 image coding architecture. To reduce
      packet losses, controlled amounts of redundancy are added to the wavelet
      transform coefficients to produce multiple descriptions of wavelet coefficients
      during the compression process to produce multiple descriptions bit-stream of a
      compressed image. Even if a receiver gets only parts of descriptions (other
      descriptions being lost), it can still reconstruct image with acceptable quality.
      Specifically, the scheme uses not only high-performance wavelet transform to
      improve compression efficiency, but also multiple descriptions technique to
      enhance the robustness of the compressed image that is transmitted through
      unreliable network channels.

PMID- 14663854
TI  - Hybrid internal model control and proportional control of chaotic dynamical
      systems.
AB  - A new chaos control method is proposed to take advantage of chaos or avoid it.
      The hybrid Internal Model Control and Proportional Control learning scheme are
      introduced. In order to gain the desired robust performance and ensure the
      system's stability, Adaptive Momentum Algorithms are also developed. Through
      properly designing the neural network plant model and neural network controller,
      the chaotic dynamical systems are controlled while the parameters of the BP
      neural network are modified. Taking the Lorenz chaotic system as example, the
      results show that chaotic dynamical systems can be stabilized at the desired
      orbits by this control strategy.

PMID- 14663855
TI  - A SISO mixed H2/l1 optimal control problem and its solution.
AB  - Study of the SISO mixed H(2)/l(1) problem for discrete time systems showed that
      there exists a unique optimal solution which can be approximated within any
      prescribed missing error bound in l(2) norm with solvable suboptimal solutions
      and solvable superoptimal solutions.

PMID- 14663856
TI  - Neural network approach for modification and fitting of digitized data in reverse
      engineering.
AB  - Reverse engineering in the manufacturing field is a process in which the
      digitized data are obtained from an existing object model or a part of it, and
      then the CAD model is reconstructed. This paper presents an RBF neural network
      approach to modify and fit the digitized data. The centers for the RBF are
      selected by using the orthogonal least squares learning algorithm. A
      mathematically known surface is used for generating a number of samples for
      training the networks. The trained networks then generated a number of new points
      which were compared with the calculating points from the equations. Moreover, a
      series of practice digitizing curves are used to test the approach. The results
      showed that this approach is effective in modifying and fitting digitized data
      and generating data points to reconstruct the surface model.

PMID- 14663857
TI  - A robust tolerance design method based on process capability.
AB  - This paper presents a method for robust tolerance design in terms of Process
      Capability Indices (PCI). The component tolerance and the suitable manufacturing
      processes can be selected based on the real manufacturing context. The robustness
      of design feasibility under the effect of uncertainties is also discussed. A
      comparison between the results obtained by the proposed model and other methods
      indicates that robust and reliable tolerance can be obtained.

PMID- 14663858
TI  - Inversion of thicknesses of multi-layered structures from eddy current testing
      measurements.
AB  - Luquire et al.'s impedance change model of a rectangular cross section probe coil
      above a structure with an arbitrary number of parallel layers was used to study
      the principle of measuring thicknesses of multi-layered structures in terms of
      eddy current testing voltage measurements. An experimental system for multi
      layered thickness measurement was developed and several fitting models to
      formulate the relationships between detected impedance/voltage measurements and
      thickness are put forward using least square method. The determination of multi
      layered thicknesses was investigated after inversing the voltage outputs of the
      detecting system. The best fitting and inversion models are presented.

PMID- 14663859
TI  - A UML profile for framework modeling.
AB  - The current standard Unified Modeling Language(UML) could not model framework
      flexibility and extendability adequately due to lack of appropriate constructs to
      distinguish framework hot-spots from kernel elements. A new UML profile that may
      customize UML for framework modeling was presented using the extension mechanisms
      of UML, providing a group of UML extensions to meet the needs of framework
      modeling. In this profile, the extended class diagrams and sequence diagrams were
      defined to straightforwardly identify the hot-spots and describe their
      instantiation restrictions. A transformation model based on design patterns was
      also put forward, such that the profile based framework design diagrams could be
      automatically mapped to the corresponding implementation diagrams. It was proved
      that the presented profile makes framework modeling more straightforwardly and
      therefore easier to understand and instantiate.

PMID- 14663860
TI  - A novel method for tracking pedestrians from real-time video.
AB  - This novel method of Pedestrian Tracking using Support Vector (PTSV) proposed for
      a video surveillance instrument combines the Support Vector Machine (SVM)
      classifier into an optic-flow based tracker. The traditional method using optical
      flow tracks objects by minimizing an intensity difference function between
      successive frames, while PTSV tracks objects by maximizing the SVM classification
      score. As the SVM classifier for object and non-object is pre-trained, there is
      need only to classify an image block as object or non-object without having to
      compare the pixel region of the tracked object in the previous frame. To account
      for large motions between successive frames we build pyramids from the support
      vectors and use a coarse-to-fine scan in the classification stage. To accelerate
      the training of SVM, a Sequential Minimal Optimization Method (SMO) is adopted.
      The results of using a kernel-PTSV for pedestrian tracking from real time video
      are shown at the end. Comparative experimental results showed that PTSV improves
      the reliability of tracking compared to that of traditional tracking method using
      optical flow.

PMID- 14663861
TI  - Large eddy simulation of the gas-particle turbulent wake flow.
AB  - To find out the detailed characteristics of the coherent structures and
      associated particle dispersion in free shear flow, large eddy simulation method
      was adopted to investigate a two-dimensional particle-laden wake flow. The well
      known Sub-grid Scale mode introduced by Smagorinsky was employed to simulate the
      gas flow field and Lagrangian approach was used to trace the particles. The
      results showed that the typical large-scale vortex structures exhibit a stable
      counter rotating arrangement of opposite sign, and alternately form from the near
      wall region, shed and move towards the downstream positions of the wake with the
      development of the flow. For particle dispersion, the Stokes number of particles
      is a key parameter. At the Stokes numbers of 1.4 and 3.8 the particles
      concentrate highly in the outer boundary regions. While the particles congregate
      densely in the vortex core regions at the Stokes number of 0.15, and the
      particles at Stokes number of 15 assemble in the vortex braid regions and the rib
      regions between the adjoining vortex structures.

PMID- 14663863
TI  - A unified convergence theory of a numerical method, and applications to the
      replenishment policies.
AB  - In determining the replenishment policy for an inventory system, some researchers
      advocated that the iterative method of Newton could be applied to the derivative
      of the total cost function in order to get the optimal solution. But this
      approach requires calculation of the second derivative of the function. Avoiding
      this complex computation we use another iterative method presented by the second
      author. One of the goals of this paper is to present a unified convergence theory
      of this method. Then we give a numerical example to show the application of our
      theory.

PMID- 14663862
TI  - Sedimentation of a single particle between two parallel walls.
AB  - The sedimentation of a single circular particle between two parallel walls was
      studied by means of direct numerical simulation (DNS) and experiment. The
      improved implementation of distributed Lagrange multiplier/fictitious domain
      method used in our DNS is a promising new way for simulation of particulate
      flows. The settling behaviors of the particle are presented ranging in Reynolds
      number from 0 to about 700, which showed that our results for low Reynolds
      numbers agreed well with that reported before. Nevertheless, for higher Reynolds
      numbers our results were different from theirs. The long-term mean equilibrium
      positions in our results were all on the centerline, but not at off-center
      position as reported before. In order to validate our simulation, experiments
      were also conducted. The results showed that the sedimenting behavior simulated
      in this paper agreed well with our experiment result.

PMID- 14663864
TI  - Image segmentation based on Mumford-Shah functional.
AB  - In this paper, the authors propose a new model for active contours segmentation
      in a given image, based on Mumford-Shah functional (Mumford and Shah, 1989). The
      model is composed of a system of differential and integral equations. By the
      experimental results we can keep the advantages of Chan and Vese's model (Chan
      and Vese, 2001) and avoid the regularization for Dirac function. More
      importantly, in theory we prove that the system has a unique viscosity solution.

PMID- 14663866
TI  - Hepatitis B and U.S. Asians.

PMID- 14663865
TI  - deCODE and Wyeth in pharmacogenomics collaboration.

PMID- 14663867
TI  - Structured treatment interruption for patients with human immunodeficiency virus
      infection.

PMID- 14663868
TI  - Antimyelin antibodies in multiple sclerosis.

PMID- 14663869
TI  - Antimyelin antibodies in multiple sclerosis.

PMID- 14663870
TI  - Chemotherapy for bladder cancer.

PMID- 14663871
TI  - Lost in translation.

PMID- 14663872
TI  - Lost in translation.

PMID- 14663873
TI  - [Criteria for assessment of endogenous intoxication in burn trauma].
AB  - Registered in patients with burn trauma was the presence of endogenous
      intoxication (EI), which was determined by a higher value of coefficient CLP/AOS,
      a higher contents of medium-molecular peptides (MMP), a lower total and effective
      concentration of albumin (TAC and EAC) and by a reserve of the binding albumin
      ability. Intoxication coefficients, i.e. IC MMP/EAC and IC C/EAC showing the
      deposition and binding of toxic ligands, were acknowledged as the most
      informative EI parameters.

PMID- 14663874
TI  - [Analysis of potassium and sodium in blood: problems of choosing a method].

PMID- 14663875
TI  - [Urine medium weight molecules in assessment of the kidney status in newborns].
AB  - The results of examinations of 66 newborns were used to suggest a new approach
      for evaluating the curves of medium urea molecules (calculations of the relative
      area beneath the curve and of areas of the first and second maxima). Issues
      related with the impact excreted by medication, endogenous intoxication and by a
      direct lesion to the renal tissues on a level of medium urea molecules are under
      discussion.

PMID- 14663876
TI  - [Analysis of protein- and oligomer-bound fucose in blood serum].
AB  - A new method was suggested that provides for a simultaneous determination of
      protein- and oligomer-bound fucose in blood serum. The level of such compounds in
      blood serum was shown to be increasing with age and in certain diseases.

PMID- 14663877
TI  - [Kinetics of free-radical oxidation of blood serum as an indicator of tumor
      effect on organism].
AB  - The experiments were made with 83 outbred male rats with transplanted sarcoma-45.
      The method of initiated chemiluminescence (CL) was used to measure the parameters
      of blood-serum lipid peroxidation in the animals. The index of free-radical blood
      serum lipid peroxidation was shown to reflect in rats the tumor-body ratio.
      Initially, the kinetic parameters of induced CL were significantly increasing,
      which was accompanied by a minor remission of the tumor volume. The subsequent
      stages of tumor growth were associated with increasing, parameters in the studied
      enzymes' activity, which is apparently related with the expression of genes
      crucial for the body's antioxidant properties. This enables the tumor cells to
      escape the monitoring of non-specific cellular immunity with the result being an
      uncontrollable tumor-volume growth.

PMID- 14663878
TI  - [Clinical significance of assessment of the metabolism of connective-tissue
      biopolymers in patients with type 1 diabetes mellitus and with diabetic
      nephropathy].
AB  - The purpose of the case study was to define a degree of destructive changes in
      the connective tissue at different stages of diabetic nephropathy (DN)
      progression. One hundred and twenty eight DN patients with type 1 diabetes
      mellitus, disease duration-5 to 20 years (classification according C. Mogensen,
      1983) were examined. Special biochemical tools were used to evaluate the
      connective-tissue condition. The parameters of metabolism of the connective
      tissue biopolymers were investigated in blood, urea and saliva, i.e. general and
      sulphated glucosamine glycine (GAG), sialic acid (SA) and oxyproline fractions.
      The results showed an increasing value of total and sulphated GAG and SA with a
      worsening DN severity, which is indicative of a destruction degree of
      glycoprotein-complexes in the microvascular basal membranes. A high level of
      bound oxyproline fractions denotes the fibril-genesis processes, which start to
      activate yet at the preclinical DN stage. The changes detected previously in the
      parameters of metabolism of the connective-tissue biopolymers, as observed in DN
      patients, ensure a timely choice of a therapy and a proper monitoring of its
      efficiency.

PMID- 14663879
TI  - [Kell blood group system of erythrocytes (literature review)].

PMID- 14663880
TI  - [ANF-associated diseases ( lecture)].

PMID- 14663881
TI  - [Antioxidant system of platelets in patients with ovary cancer].
AB  - The activities of lipid peroxidation and of platelets' antioxidant protection
      were investigated in 30 healthy women and in 44 patients with primarily diagnosed
      different-stage ovary cancer (OC). An essentially higher activity of superoxide
      dimutase (SOD, by 2.5 times) and of catalase (by 1.5 times) was detected in
      platelets of OC patients versus the norm. A simultaneous increase of malonic
      dialdehyde (MDA) by 2.5 times denotes a free-radical activation. There was also
      an insignificant growth of the glutathione level, whereas the activity of
      glutathione-S-transferase (GST) did not virtually change. A comparative analysis
      of the biochemical indices of patients with different stages of the disease
      revealed valuable distinctions related with a higher activity of SOD and catalase
      in stages 3-4 versus the initial stages. Notworthility, the MDA level was
      decreasing. Minor changes in the system of glutathione are not obviously decisive
      in impairing the regulatory mechanism of antioxidant protection in platelets
      unlike in malignant cells. The results provide a solid basis for assuming that
      the impact made by deranged regulations of free radicals on the platelet chain in
      the hemostasis system causes changes in the blood rheological properties
      entailing a higher aggregation of platelets, thus, triggering the onset of
      platelet-embolic complications in the discussed patient category. The impaired
      regulation mechanism of antioxidant protection in platelets is a major
      manifestation of the oxidant stress evolving due to a growing tumor; the
      mechanism is important for evaluating the structural-and-functional platelets'
      condition.

PMID- 14663882
TI  - [Phagocytosis of polymer microspheres immobilized with bioligands by peripheral
      blood leukocytes in patients with acute pancreatitis].
AB  - Phagocytosis of polymer microspheres both modified and unmodified by bioligands
      (gelatin, fibronectin and A protein) by leukocytic blood cells of patients with
      acute pancreatitis. The presence of bioligands in the surface of polymer
      microspheres and their activity were monitored by the reaction of latex
      agglutination with an appropriate ligand being involved. The study resulted in
      designing a method of phagocytosis implementation that can be used to evaluate
      the content of certain receptors in cellular membranes and, subsequently, to
      define the changed receptor cell apparatus caused by a disease. The nature of
      polymer microspheric bioligands immobilized to the surface was shown to influence
      significantly the activity of leukocytic blood cells.

PMID- 14663883
TI  - [Cytological tests in preventive gynecological examinations].

PMID- 14663884
TI  - [Laboratory diagnostics of Crimean hemorrhagic fever by polymerase chain
      reaction].
AB  - Our group developed, within the present case study, two techniques' variations,
      i.e. a single-step RT-PCR and nested RT-PCR assays, for the purpose of detecting
      the Crimean-Congo hemorrhagic fever RNA virus in human samples. The above assays
      as well as those previously recommended by the Ministry of Health of the Russian
      Federation were simultaneously used in 14 clinical samples obtained from patients
      with Crimean hemorrhagic fever. After assessing the detection accuracy, it was
      found that the developed-by-us test system displayed the same or even better
      diagnostic values versus the previously recommended nested RT-PCR and a 1000-fold
      advantage over the previously recommended single-step RT-PCA. The single-step RT
      PCR assay variation is always more preferable in sense of technical and economic
      motivations. Finally, the test system developed by us has every reason to become
      the method of choice in routine PCR diagnosis of Crimean hemorrhagic fever after
      all official trials and approvals are duly complied with.

PMID- 14663886
TI  - [Characteristics of distribution of nitric oxide synthase containing neurons in
      the medullary cardiovascular centers of dogs and rats].
AB  - The aim of the study was to characterize species-related differences in the
      distribution of nitric oxide synthase (NOS)-containing neurons in the medullary
      structures of dogs and rats involved in the regulation of the sympathetic or
      parasympathetic drives. Two main results have been obtained, namely: (i) the
      average number of NOS-containing neurons in the dorsomedial and ventrolateral
      medulla per section in dog was larger than that in rat, while the density of the
      positive cells in the both regions in dog was less than that in rat. (ii) Within
      the dorsal motor nucleus of vagus a lot of NOS-containing cells (preganglionic
      vagal neurons) were observed only in dog. Differences in the distribution of NO
      generating neurons in the medullary cardiovascular centers, and heterogeneity in
      the basal level of NO release may contribute to the peculiarities of the
      hemodynamic responses induced by NOS inhibitors in these species.

PMID- 14663885
TI  - [Release of unidentified substances of mitochondrial origin--evidence of
      mitochondrial permeability transition pore opening in the heart mitochondria of
      rats ].
AB  - In experiments in vitro on isolated heart mitochondria of rats, an activation of
      mitochondrial permeability transition pore (PTP) was induced by either modelling
      an oxidative stress with PTP-inductor phenylarsine oxide (PAO) or by calcium
      overload (CaCl2). PTP-opening was determined spectrophotometrically (lambda = 520
      nm) by a decrease in an optical density (OD), resulting from mitochondrial
      swelling. We also observed a release of mitochondrial unidentified substances
      (mitochondrial factor, MF) registered spectrophotometrically in a range of waves
      lambda = 230-260 nm. Both correlation between mitochondrial swelling and a
      release of the mitochondrial factor have been found in experiments with PAO at
      concentrations 10(-7)-10(-4) mol/l, and in those with CaCl2 at concentrations 10(
      6)-10(-4) mol/l. The classical inhibitor of mitochondrial PTP cyclosporin A (Cs
      A, 10(-5) mol/l) inhibited mitochondrial swelling and a release of that factor
      completely. Our experimental data give evidence for mitochondrial origin of the
      factor and its release following PTP-opening by PTP-inductors--PAO and CaCl2.
      Mitochondrial swelling that accompanied the factor's release might contribute to
      PTP-opening and be useful in defining the mitochondrial sensitivity either with
      inductors or inhibitors of mitochondrial PTP in different tissues under normal
      and pathological states of organism.

PMID- 14663887
TI  - [Determination of the stable mitochondrial factor in vivo].
AB  - We have determined a release of a stable mitochondrial factor (SMF) into the
      outflowing blood in vivo. That effect was induced by ischemia/reperfusion or
      phenylarsin oxide (PAO)--the activators of the mitochondrial permeability
      transition pore (MPTP) and the oxidative stress. The SMF was measured by a
      spectrophotometer in the range of wave-lengths 230-260 nm with the absorption
      maximum of 240-250 nm. The SMF release was accompanied with a decrease in the
      myocardial contractility, disturbances in cardiodynamics and regional blood
      circulation. The data obtained have demonstrated that the SMF can be used as a
      marker of MPTP opening in vivo.

PMID- 14663888
TI  - [Permeabilized salivary gland cells as a model to study Ca2+-transporting systems
      of endoplasmic reticulum membrane].
AB  - A method for chemical permeabilization of secretory cells of rat submandibular
      salivary gland has been elaborated. It was shown that the effects of digitonin on
      total calcium content in permeabilized acinar cells and protein content in their
      incubation medium correlated with concentration and duration of the detergent
      treatment. Digitonin-permeabilized acinar cells perform Ca(2+)-dependent protein
      secretion, which level depends on the duration of cell incubation in an
      intracellular buffer solution. The ability of permeabilized acinar cells to
      perform thapsigargin-sensitive ATP-dependent Ca2+ transport was established by
      using biochemical approaches and monitoring of the intrareticular calcium
      concentration with mag-fura 2 dye. Thapsigargin-insensitive Ca2+ store in the
      permeabilized acinar cells of the salivary gland was shown to be also available.
      Thus, these data give evidence to conclude that digitonin-permeabilized secretory
      cells of the submandibular salivary gland are an adequate model to study the
      mechanisms of Ca(2+)-dependent control of the exocytosis and membrane Ca(2+)
      transporting systems of the intracellular calcium stores.

PMID- 14663889
TI  - [Suppression of visceral pain by action of the low intensity polarized light on
      acupuncture antinociceptive points].
AB  - In experiments on mice, statistically authentic weakening of visceral pain has
      been shown after an action of low intensity polarized light from a device
      Bioptron on antinociceptive acupuncture points (AP). Pain was caused by an
      intraperitoneal injection of 2% acetic acid (0.1 ml/10 g). The intensity of pain
      was judged on duration and frequency of painful behavioral reactions (writhing,
      licking of abdomen), as well as on duration of sleep, eating and motor activity.
      In animals which immediately after injections of acetic acid were exposed to
      polarized light of low intensity for 10 min, applied on any of antinociceptive
      APs (E-36, E-43, VC-8, RP-6), the duration of painful behavioral reaction was
      determined to be reduced, while that of non-painful one increased. The comparison
      of the total duration of the writhing at control and experimental mice showed
      that an activation of AP E-43 induced the greatest analgesic effect (76.5%), from
      AP VC-8 it was 76.3%, from RP-6--46.8%, and from E-36--41.4%. We have concluded
      that the effect of polarized light of low intensity on APs was a convenient non
      pharmacological method of treating visceral pain.

PMID- 14663890
TI  - [Effect of modulator of the signal transmission from opioid receptor to sodium
      channels on hypothalamus self-stimulation].
AB  - We investigated effects of different doses of a new preparation comenic acid as a
      modulator of the transmission of signals from an opioid receptor to slow sodium
      channels on the hypothalamic rewarding system in male Wistar rats. Comenic acid
      has been shown to inhibit the reaction of the hypothalamic self-stimulation (SS)
      in a dose-dependent fashion with the strongest effect at doses of 28.8-30 mg/kg.
      We observed a decrease in the rate of lever-pressings, induced by the threshold
      for SS current intensity, and an increase in the threshold for the response of
      SS, or its cessation. The similar suppressing effect of the preparation was found
      at its repeated injections. Thus, those results showed that comenic acid failed
      in both activation of the rewarding system of the lateral hypothalamus and
      adaptation to it.

PMID- 14663891
TI  - [Effect of chronic acidosis on protein metabolism].
AB  - In experiments on mongrel albino male rats, we studied the effects of 30 mmol/kg
      lactic acid, 30 mmol/kg NaHCO3, and 20 mmol/kg NH4Cl (intraventricular
      injections, daily for 7 days) on the contents of total protein, residual
      nitrogen, urea, and creatinine in the blood, as well as on the activities of
      aldolase and alanine aminotranspherase (ALT). We also studied the effects of the
      above agents on renal functions: glomerular filtration rate (GFR), diuresis, and
      excretion of ammonium, creatinine, and protein with urine. We have found that
      chronic, hyperchloremic, and lactic acidosis resulted both in a significant
      decrease in the levels of protein and residual nitrogen and in an increase in the
      concentration of the urea; these phenomena were accompanied by a considerable
      intensification of the urinary NH4+ excretion. In contrast, under conditions of
      chronic alkalosis we observed a drop in the level of urea in the blood with no
      changes in the concentrations of protein and residual nitrogen, as well as a
      dramatic depression of the urinary NH4+ excretion. In that case, the
      concentration of creatinine in the blood, GFR, diuresis, and excretion of
      creatinine and protein with urine did not correlate with the above-mentioned
      changes in protein metabolism. In all experiments, the activities of aldolase and
      ALT preserved their normal level giving evidence against damage to the liver.
      These results give evidence for spending a great number of amino acids on the
      renal ammoniogenesis at chronical acidosis; their saving at alkalosis; an
      impairment of the protein synthesis, and an increase in protein catabolism at
      acidosis to replenish the pool of amino acids, as well as for an activation of
      the urea synthesis to eliminate the excessive amount of NH4+ from the blood.

PMID- 14663892
TI  - [Effect of modification in fatty acid composition of membrane phospholipids on
      reaction of isolated heart in acute ischemia-reperfusion].
AB  - The aim of this study was to evaluate the effects of a diet supplemented with
      omega-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic) and
      tocopherol, which are the base of a preparation "Tekom", on a composition of
      myocardial phospholipid fatty acids, as well as on the metabolism of eicosanoids,
      free radical processes and the contractility of isolated working heart in rats at
      ischemia/reperfusion. Added to the diet within 4 weeks, "Tekom" induced an
      increase in the content of omega-3 polyunsaturated fatty acids in membranes of
      cardiomyocytes, a decrease in vasoactive metabolites of arachidonic acid and
      limitation of free radical processes. "Tekom" inhibited cardiac arrhythmias in
      the isolated working hearts of rats and improved the cardiac pump function at
      ischemia/reperfusion.

PMID- 14663893
TI  - [Effect of alantone on mast cells and hemostasis].
AB  - In experiments on rats it has been shown that under the influence of alantone (50
      mg/kg of the body weight daily during 30 days) a number and level of maturity of
      peritoneal and mesenteric mast cells increased, and blood clotting decreased. It
      might be important for the well-known ability of alantone to increase both the
      peripheral blood circulation and microcirculation.

PMID- 14663894
TI  - [Effect of stress on calcium homeostasis in muscular tissues].
AB  - A dynamics of the content of calcium (Ca) in aorta, heart and skeletal muscles
      was studied in rats exposed to a stress factor for 21 weeks. We observed a 7-fold
      increase in its content in all the organs examined by the middle of an experiment
      and its progressive decrease by the 21-st week. It might result from the stages
      of stress and development of hypercholisterinemia. An inhibitor of L-type calcium
      channels niphidipine did not change the dynamics of Ca content qualitatively but
      it decreased its quantitative parameters, especially at final stages of
      experiments. We suggest that possible mechanism of keeping calcium homeostasis in
      the organs examined at different stages of stress is an intensive work of ligand-
      and potential-dependent calcium channels.

PMID- 14663895
TI  - [Study of apoptosis manifestations in streptozotocin diabetes mellitus].
AB  - The aim of this work was to study manifestations of apoptosis in pancreas, brain
      and myocardium of rats at the type I diabetes mellitus. To reveal the apoptotic
      changes in cells, specific damages of DNA were identified by the TUNEL-method.
      Specific for apoptosis changes in chromatin and cell membranes were found after
      counterstaining of a specimen by methyl green. In addition, the apoptotic and non
      apoptotic cells were differentiated automatically with the help of image
      analyzing computer system by an index of optical density of cellular nucleus.
      This method allowed to find out for sure that apoptotic cells were available in
      all the studied tissues of healthy animals. However the possibility of their
      revealing by the TUNEL-method depends on the way of tissue fixation. Development
      of the type I diabetes mellitus was accompanied with an increase in the number of
      such cells, which gives evidence for an important role of apoptosis in diabetes
      pathogenesis.

PMID- 14663897
TI  - [Copper content in the blood of irradiated animals].
AB  - We studied effects of a single total irradiation by 60Co gamma-quantums on the
      content of copper in the blood of male rats in 0.5, 1, 2, 4, 6, 8, 10, 15, 20,
      35, 45, 60, 90 and 120 days after exposing to irradiation. Maximal rate of
      changes in the content of copper in the blood of rats took place in 2-8 days
      after irradiation and were dose-dependent.

PMID- 14663896
TI  - [Effect of time of day and fatigue on psychophysiological functions of an
      operator].
AB  - Time of the day has been found to have an important effect on the intersystemic
      relations of the psychophysiological functions of an operator, while the activity
      of the cardiovascular system (CVS) depended not only on the time of the day but
      also, to a large extent, on fatigue. The morning time potentiated the
      manifestations of staying awake but the evening time--those of fatigue.
      Relatively less pronounced changes in the functioning of an organism in the
      morning, induced by fatigue, gave evidence for both a higher level of activation
      of the organism and relatively higher level of the central interactions in it.
      Accumulated fatigue potentiated the manifestations of daily variations of the
      functional activity of an operator. The second subsequent night shift has been
      shown to have a higher initial activity of the CVS, as compared to the second day
      shift, and it was characterised by an increased difference between systolic and
      diastolic blood pressure as compared to the first night shift. Effect of
      overshift fatigue shows an increase in the vascular component and a decrease in
      the cardiac one in the regulation of blood circulation. Mental performance was
      shown to be less dependent on time of the day and fatigue as compared to the CVS
      activity. Short-term memory was more sensitive to fatigue and more often
      correlated with the parameters of the CVS than attention did.

PMID- 14663898
TI  - Myelination and demyelination processes in the rat cerebellum cell culture: an
      electron microscopic study.
AB  - We observed manifestations of the myelination process in dissociated culture of
      the cerebellar tissue of newborn rats and modifications of the structure of
      myelin sheaths after treating the culture with a demyelinating factor, blood
      serum of patients suffering from multiple sclerosis (MS). On day in vitro (DIV)
      26, in the control myelin sheaths of the axons demonstrated the closest
      resemblance to those observed in vivo, and we selected this term for inducing
      demyelination. Addition of the serum of MS patients to the culturing medium
      evoked rapid (in 3-6 hours) dramatic changes in the ultrastructure of myelin
      sheaths; these were a decrease in the number of the lamellae, their splitting and
      invagination, formation of vesicles, etc. The serum of MS patients in an acute
      stage of the disease exerted more intensive demyelination effects than that of
      patients in a remission stage.

PMID- 14663899
TI  - [Comparative efficacy of the laparotomic and laparoscopic operative procedures in
      patients with an acute biliary pancreatitis].
AB  - Comparative estimation of the laparotomic and laparoscopic operative
      interventions efficacy was done in 75 patients with an acute biliary
      pancreatitis. In control group included 39 patients, operated using laparotomic
      access, in main group--36 patients, in which was done diagnostic and medical
      laparoscopic interventions. Application of laparoscopy have allowed to establish
      diagnosis, form of disease, presence of peritonitis and determinate medical
      tactics. In emergent order operated 8 (22.2%) patients with acute phlegmonous
      cholecystitis in combination with noninfected pancreatonecrosis. In 28 (77.8%)
      patients were performed medical laparoscopic interventions with endoscopic
      papillosphincterotomy.

PMID- 14663900
TI  - [Application of sorbilact for treatment of postoperative paralytic ileus in
      cancer of the esophagus and stomach].
AB  - For prophylaxis and treatment of ileus in 12 patients after performance of
      radical operation for esophageal and gastroesophageal carcinoma, since the end of
      the first day during subsequent 4 days postoperatively sorbilact was infused
      intravenously twice a day. Terms of the intestinal peristalsis restoration,
      passage of flatus, spontaneous defecation restoration were shorter, than after
      application of generally accreted treatment.

PMID- 14663901
TI  - [Subtotal and total colectomy with formation of primary anastomosis for left
      colonic ileus of tumoral genesis].
AB  - The one-staged subtotal/total colectomy with formation of primary ileo
      sigmoanastomosis or ileo-rectal anastomosis is applied in tumoral left colonic
      ileus. There were estimated immediate results and the role of the method in the
      treatment of 46 patients with left colonic obstructive tumor. Postoperative
      complications had occurred in 52% of the patients, postoperative mortality had
      constituted 10.9%. Performance of subtotal/total colectomy with formation of
      primary anastomosis constitutes the alternative and preferable method of
      treatment of patients with left colonic obstructive tumor.

PMID- 14663902
TI  - [Application of magnetic therapy in acute paraproctitis].
AB  - There were studied the possibilities and perspectives of application of the
      magnetically liquefied layer as an instrument for better purulent and
      putrefactive wounds clearance after intervention for an acute paraproctitis.
      Together with clinical signs the results of bacteriological investigation were
      controlled as well. There was established high efficacy of the method proposed
      and expedience of its application.

PMID- 14663903
TI  - [The course of hyperlipidemia in obliterating atherosclerosis of the abdominal
      aorta and its branches].
AB  - There was the hyperlipidemia typing performed, basing on analysis of the
      biochemical and laboratory investigation data, conducted in 107 patients with
      obliterating atherosclerosis of the abdominal aorta and the lower extremities
      main vessels. There was established, that for patients with occlusive-stenotic
      affection of abdominal aorta and its branches the presence of hyperlipidemia type
      IIa is characteristic.

PMID- 14663904
TI  - [Restorative operations on main vessels for diabetic angiopathy of lower
      extremities with purulent-necrotic complications].
AB  - There were analyzed the results of treatment of 75 patients with diabetic
      angiopathy of the lower extremities and purulent-necrotic affection of the foot
      tissues, to whom restoration operation on the main vessels was accomplished. In
      11 patients aorto-femoral bilateral shunting together with lumbar sympathectomy
      was performed, in 7--femoro-femoral shunting, in 38--femoro-popliteal, in 12-
      iliofemoral shunting together with lumbar sympathectomy, in 7-
      thrombendarterectomy from a. femoris communis in conjunction with the vessel
      dilatation using the patch. In 89.2% of patients satisfactory result with the
      extremity preservation was noted. In 10.8% of patients high amputation of
      extremity was done, all the patients are alive.

PMID- 14663905
TI  - [Diagnostics and treatment of varicocele as a symptom of renal venous
      hypertension].
AB  - From the year 1997, we examined 61 patients with left-sided varicocele aged 9-28
      years. Nine (14.7%) of them had a recurrence of the disease after intervention
      (Ivanissevich operation). The renal venous hemodynamics was evaluated in order to
      choose the right method of surgery. All patients underwent surgery, the results
      were positive. The operation of testicular vein was conducted together with
      excision of varicous scrotal veins.

PMID- 14663906
TI  - [Treatment of trophic ulcers using the method of constant vacuum extraction].
AB  - The results of application of constant vacuum extraction, a new method of the
      lower extremities trophic ulcers treatment, are adduced. There was shown the
      method efficacy in the treatment of the varicose disease complications, there
      were noted the reduction of the wound healing terms in comparison with such using
      conventional methods of treatment, the advantages and peculiarities of the method
      as well.

PMID- 14663907
TI  - [Clinical and functional characteristics of patients late after pneumonectomy
      with complicated course of postoperative period].
AB  - Results of examination of 65 patients, to whom twenty years before pneumonectomy
      was performed for pulmonary tuberculosis and chronic nonspecific pulmonary
      diseases, were analyzed. Peculiarities of postoperative period course were
      determined in patients with early complications, including the tuberculosis
      reactivation. Methods of examination: clinical investigation, standard laboratory
      tests, bacteriologic investigation of phlegm, roentgenography, multiradial
      roentgenoscopy of thoracic cage, bronchography, computeric tomography,
      roentgenokymography, spirography, pneumotachometry. Specific and nonspecific
      changes in lungs, which resided, were revealed accordingly in 20 and 23.3%
      patients. The tuberculosis reactivation is possible twenty years after the
      operation. Pneumonectomy performance permits to eliminate an active tuberculosis
      in 70-80% patients. The tuberculosis changes in residual lung worsen the patients
      quality of life after pulmonectomy performance due to progress of respiratory
      insufficiency.

PMID- 14663908
TI  - [Intratumoral chemotherapy in the treatment of regional widespread pulmonary
      cancer].
AB  - A new method of treatment of pulmonary cancer using the introduction of
      cytostatic drugs and prednisolone into the tumor during bronchofibroscopy was
      suggested. This increases the effectiveness of treatment and reduces the side
      effects of drugs. Complete regression of tumor was observed in 9 (32.1%) patients
      of the main group, partial regression--in 12 (42.9%). In control group the
      regression was observed in 6 (20%) and in 10 (33.3%) patients, respectively.

PMID- 14663909
TI  - [Treatment of acute pyopneumothorax during the tuberculosis epidemic].
AB  - Pathogenetical mechanisms of pyopneumothorax formation that cause hypoxia-
      hypoxemia, decreased cardiovascular function and intoxication have been
      described. The existing approach leads to the progression of disease, and the
      majority of patients die within the next 1.5-2 years. The immediate surgery (step
      by-step thoracoplasty with modelling of parietal pleura on the terms of
      pneumoperitoneum) were suggested. Positive statistical data are provided.

PMID- 14663910
TI  - [Plasma fibronectin in patients during toxic goiter surgery and early
      postoperative period].
AB  - In 63 patients with toxic goiter the fibrinonectin content in plasma and its
      cryoprecipitate activity (CPA) were studied during surgical treatment conduction.
      There were revealed lowering of its level and CPA with subsequent lowering of
      this indexes in postoperative period. Application of uni-group heparinized
      freshly frozen plasma in therapeutic complex was proposed for hypofibronectinemia
      correction and for reduction of postoperative thyreotoxicosis severity.

PMID- 14663911
TI  - [Immuno-bacteriological characteristics of septic shock in children of early
      age].
AB  - During bacteriological investigation, conducted in children of early age for
      generalized septic state in the septic shock (SS) period, there was established
      predominance of gramnegative conditionally pathogenic microorganisms. Initially
      there was noted the increase of peroxidal oxidation of lipids (POL) intensity
      with suppression of cellular and humoral immunity factors. Application of the
      medical plasmapheresis method and immunoglobulin in complex treatment of SS
      renders stimulative influence on homeostasis, promotes favourable course of the
      disease, prevention of complications.

PMID- 14663912
TI  - [Two-year experience of laparoscopic operations in the Zhitomir regional
      pediatric hospital].
AB  - First experience of laparoscopic operations performance in children in the
      Zhytomir region was suggested as well as the advantages of laparoscopy, method of
      "open laparoscopy", variant of assisted laparoscopy and laparotomy under
      laparoscopic control. The analysis of results of laparoscopic interventions in
      205 children, 36--emergent and 169--planned, was conducted.

PMID- 14663913
TI  - [Preoperative patient blood preservation as an alternative to donor blood
      transfusion during joint endoprosthesis surgery].
AB  - In 79 patients, to whom total endoprosthesis of the knee and hip joints were
      performed, the efficacy of preoperative blood preparation was studied up. The
      method is effective and secure alternative to the donor blood transfusion in
      orthopedic surgery. Taking into account the ability of patient with rheumathoid
      arthritis to restore the hemoglobin level, the expediency of preoperative blood
      preparation in them must be determined individually.

PMID- 14663914
TI  - [Portal hypertension complicated by hemorrhage originated from the dilated
      esophageal veins].

PMID- 14663915
TI  - [Interrelationship of neutrophilic granulocytes, endotheliocytes and mononuclear
      macrophages in occurrence and course of purulent-septic states. Communication 2.
      Antimicrobic activity of neutrophilic granulocytes].

PMID- 14663916
TI  - [Method of gallbladder excision with cholecystostomy].

PMID- 14663917
TI  - [Device for cutting out of cutaneo-fascial flap during leg amputation].

PMID- 14663918
TI  - [The endoscopic laser excision of hamartoma and foreign body of the main
      bronchus].

PMID- 14663919
TI  - [Observation of giant cyst of spleen after abdomen blunt trauma].

PMID- 14663920
TI  - Time perspective and health-promoting behavior in a cardiac rehabilitation
      population.
AB  - Behavior changes can significantly improve outcomes for patients in the cardiac
      rehabilitation population. The authors examined the influence of time
      perspectives on health-promoting behaviors of patients for whom the future might
      be perceived as limited, although goal-directed behavior changes are crucial.
      Measures included the Zimbardo Time Perspective Inventory and the Health
      Promoting Lifestyle Profile II (HPLPII). In this study of 74 cardiac participants
      with a mean age of 60.2 years, the preponderant time perspective was found to be
      past-positive orientation. The authors discuss the effects of a life-threatening
      event and older age on time perspective and health-promoting behaviors and
      consequent implications for cardiac rehabilitation programs.

PMID- 14663921
TI  - A comparison of physical activity of posttreatment breast cancer survivors and
      noncancer controls.
AB  - The authors obtained data from 335 breast cancer survivors and 6,880 noncancer
      controls. They proposed (1) to determine whether, after treatment, the survivors
      were meeting the Center for Disease Control and Prevention/American College of
      Sports Medicine recommendations for physical activity and were similar to the
      controls in physical activity and (2) to compare the modes of activity of the 2
      groups in frequency, min/session, and sessions/wk. Adjusted logistic regression
      analyses revealed that the breast cancer survivors engaged in as much moderate,
      vigorous, and combined physical activity as the noncancer controls did. However,
      chi-square analyses showed that survivors engaged in more yard work than the
      controls did, whereas independent-sample t tests showed that the frequency and
      the total min/wk of stretching were significantly higher in breast cancer
      survivors compared with noncancer controls. Findings from the study suggest that
      breast cancer survivors engage in as much physical activity as controls do, but
      that the groups differ in specific activities.

PMID- 14663922
TI  - Sexual trauma, posttraumatic stress disorder, and health behavior.
AB  - The authors tested whether sexual traumatization is associated with poorer health
      behavior and also evaluated the role of posttraumatic stress disorder (PTSD) in
      this relationship. They mailed questionnaires to 419 women who had visited a San
      Diego Veterans Administration primary care clinic in 1998 and received 221
      responses, a 56% return rate. They found that a history of sexual assault was
      associated with increased substance use, risky sexual behaviors, less vigorous
      exercise, and increased preventive healthcare. They then used regression-based
      techniques to test whether PTSD mediates the relationship between a history of
      sexual assault and health behaviors and discovered support for this hypothesis in
      relation to substance use. PTSD symptoms were also associated with less
      likelihood of conducting regular breast self-examinations. Findings from the
      study highlight the value of programs designed to (1) identify trauma victims,
      (2) screen for problematic behaviors, and (3) intervene to improve long-term
      health outcomes.

PMID- 14663923
TI  - Physician facilitation of patient involvement in care: correspondence between
      patient and observer reports.
AB  - The authors surveyed 128 patients with type 2 diabetes mellitus (1) to evaluate
      the congruence between patients' and observers' perceptions of physicians'
      facilitation of patients' involvement in care and (2) to identify which physician
      behaviors were most closely related to patients' perceptions that their doctors
      encouraged them to be involved in their care. The patients reported the degree to
      which they perceived that their physicians encouraged their involvement in the
      medical care process. Raters blind to the study hypotheses coded audiotapes of
      the physician-patient interactions. Pearson's r and simultaneous multiple
      regression used to address the study questions indicated a small to moderate, but
      statistically significant, association between patients' perceptions and
      observers' reports concerning the physicians' levels of facilitation. Open-ended
      questions, responding to patient questions, and offering fewer alternatives were
      all associated with the patients' positive reports of physician facilitation.

PMID- 14663924
TI  - Physical and sexual abuse: risk factors for substance use among young Hungarian
      women.
AB  - The authors used a multistage stratified sampling method to conduct a cross
      sectional survey of a nationally representative sample of 3,615 Hungarian women
      aged 15 to 24 years to acquire epidemiologic data on physical and sexual abuse
      and analyze the relationship between abuse and health-risk behaviors. Just over
      30% of the young women reported having experienced some type of abuse in their
      lifetimes. All maladaptive coping strategies, especially sedative use, were more
      prevalent among those who had experienced physical abuse. The prevalence of
      smoking, drinking alcohol, and experimenting with drugs was closely related to
      both physical and sexual abuse. Having experienced abuse is an important factor
      in young women's development of risky health behaviors. Clinicians should screen
      for abuse in this age group to prevent behaviors that lead to long-term health
      problems.

PMID- 14663925
TI  - Pancreatic tumours with cystic features.

PMID- 14663926
TI  - [Serous microcystic adenoma of the pancreas: cytologic and histologic features].
AB  - Cytologic and histologic features in a case of serous microcystic adenoma of the
      pancreas in a 61-year-old female are presented. In fine-needle aspiration
      materials, epithelial cells arranged singly, in small clusters and in monolayer
      sheets were found. The neoplastic cells had round to oval nuclei with finely
      distributed chromatin and inconspicuous nucleoli. Nuclear atypia and mitoses were
      not seen. The cytoplasm was moderately abundant and finely granular.
      Histologically, the encapsulated tumor was composed of multiple small cysts lined
      by a single layer of flat to cuboidal cells. The tumor cells contained clear
      cytoplasm with glycogen and centrally located round to oval nuclei with
      inconspicuous nucleoli without any atypia. Mitoses were absent. The intervening
      stromal septa were hypocellular. Immunohistochemically, the tumor cells revealed
      diffuse positivity of cytokeratins and epithelial membrane antigen. Proliferative
      antigen Ki-67 was positive only in sporadic cells. No immunoreactivity for
      vimentin, carcinoembryonal antigen and S-100 protein was found. Chromogranin A
      and synaptophysin were expressed only in Langerhans' islets in the tumor capsula.
      In differential diagnosis, it is important to distinguish serous microcystic
      adenoma mainly from lymphangioma, cavernous hemangioma, serous
      cystadenocarcinoma, mucinous cystadenoma or cystadenocarcinoma, solid and
      pseudopapillary epithelial tumour, acinar cell cystadenocarcinoma, renal cell
      carcinoma and mesothelioma.

PMID- 14663927
TI  - [Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of
      the pancreas].
AB  - Apoptosis plays a central role in the development and/or progression of cancer.
      There are several methods for detection of apoptotic cells in tissue sections
      including light and electron microscopy, in situ nick end-labeling (ISEL), TdT
      mediated dUTP nick-end labeling (TUNEL) and immunohistochemical detection of
      proteins associated with apoptosis. Apoptosis was assessed by the monoclonal
      antibody M30 CytoDEATH (M30), which is specific for neo-epitope in cytokeratin 18
      that becomes available at an early caspase cleavage during apoptosis. Expression
      of bcl-2 protein was evaluated, because bcl-2 protein plays an important role in
      the regulation of apoptosis. Twenty-six invasive ductal adenocarcinomas of the
      pancreas were studied immunohistochemically with antibodies M30 and bcl-2. The
      mean apoptotic index (AI, the percentage of apoptotic cells of the total tumor
      cells number) was 2.75%. High AI (> 10%) was observed in 4 cases of the 26
      pancreatic carcinomas (15%). Protein bcl-2 was expressed in 3 cases (11.5%). The
      AI did not correlate with the expression of protein bcl-2. In conclusion, the
      detection of neo-epitope in cytokeratin 18 by monoclonal antibody M30 can be used
      for quantification of apoptotic cells with immunohistochemical techniques in
      tissue sections. It is a new approach to evaluate apoptosis in pancreatic
      carcinomas. The low positivity of bcl-2 expression in pancreatic adenocarcinomas
      suggests that bcl-2 protein does not play a central role in pancreatic
      tumorigenesis and cancer progression.

PMID- 14663928
TI  - [What is your diagnosis? Lobular carcinoma in situ (LCIS) in sclerosing
      adenosis].

PMID- 14663929
TI  - [Immunohistochemical detection and quantification of minimal residual disease
      using DBA.44 antibodies in trephination biopsies of hairy cell leukemia].
AB  - Hairy cell leukemia patients treated with 2-chlorodeoxyadenosine or 2
      deoxycoformicin achieve a very high number of therapeutic responses. After
      complete remission, i.e. minimal residual disease, we cannot demonstrate the
      disease activity, splenomegaly, or lymphadenopathy; moreover, there comes to
      normalization of hemoglobin concentration, leukocyte count, and platelet count.
      No leukemic cells in peripheral blood or bone marrow smears can be seen with the
      use of staining techniques. They can be demonstrated immunohistochemically in
      decalcified trephine bone marrow biopsies with the use of DBA.44 antibody
      together with their morphologic features. For quantification of leukemic cells we
      use LUCIA-M image analysis.

PMID- 14663930
TI  - [Microscopic disorders of cortical development of the brain and its
      etiopathogenic importance for detection in patients with temporal epilepsy
      associated with hippocampal sclerosis].
AB  - Hippocampal sclerosis represents a common structural basis of temporal lobe
      epilepsy. However, the etiological factors and mechanisms leading to its
      development still remain unexplained. In our study, we present neuropathological
      findings in the resected hippocampus and the pole of the temporal lobe in 15
      patients with hippocampal sclerosis. "Initial precipitating injuries" that are
      thought to cause the development of hippocampal sclerosis (febrile seizures in
      early childhood, head injury or meningoencephalitis) were present in the history
      of 12 patients. In the remaining 3 cases, no predisposing factors were found.
      Attention was paid to the histopathological identification of disturbed neuronal
      migration and differentiation in the temporal lobe. These defects were observed
      in 7 cases; in three of these, no predisposing factors were stated in the
      patients' histories. We suggest that in these cases, hippocampal sclerosis arises
      due to previously undetected disorders of cortical development. A latent
      neocortical malformation may also contribute to the development of hippocampal
      sclerosis in patients with an initial precipitating injury in anamnensis.
      Histopathological examination of resected epileptic brain tissue can provide
      insights into the individual pathogenesis of epileptic disorders, especially by
      the detection of microscopic disorders of cortical development.

PMID- 14663931
TI  - [Pulmonary embolism--temporal aspects].
AB  - The post-mortem incidence of pulmonary embolism (PE) in the years 1960-2000 was
      retrospectively reviewed. In five reference years 1960, 1970, 1980, 1990 and 2000
      there was a total of 582 necropsy patients with PE encountered in 3420 autopsies
      of adults (> 18 y.)--an incidence of 17.0%. The incidence had a steadily
      declining trend--from 19.2% in 1960 to 14.2% in the year 2000. The incidence was
      higher in females (20.4%) than in males (14.4%). We have also followed the
      seasonal variation of PE incidence; this was the highest in autumn (September
      November) 18.6%, and the lowest in spring (March-May) 14.3%. The average age of
      patients who died with PE increased from 63.7 y. in 1960 to 67.8 y. in 2000; it
      was higher in females (66.9 y.) than in males (64.2 y.). Our results confirm
      those of most pathological studies that the post-mortem incidence of PE is
      declining.

PMID- 14663932
TI  - [Adenoleiomyomatous hamartoma of the lung] ].
AB  - The author described an adenoleiomyomatous hamartoma of the lung. The hamartoma
      was well circumscribed and measured 2.5 x 3.0 x 3.0 cm. This type of hamartoma is
      a rare lesion in literature described only in single cases, and without performed
      immunohistochemistry. In our case, the hamartoma was formed by slit or irregular
      glandular-like spaces lined by cuboid or columnar epithelial cells. Located
      around these spaces, fascicles and bundles of smooth muscle tissue with a
      positive antibody reaction to desmin, smooth muscle actin, and calponin, were
      found. Reaction with CD34 and S100 protein antibodies was negative. In the
      discussion, the author draws attention to disunity of terms and nomenclature of
      similar lesions. After three years of post-operative clinical follow-up, the
      patient is asymptomatic and without any signs of lung disorder.

PMID- 14663933
TI  - [History of pathologic anatomy in ancient times--part 2].

PMID- 14663934
TI  - [Detection of collagenase activity and tissue inhibitor of metalloproteinase-1
      expression level in the urethral scar tissue].
AB  - OBJECTIVE: To find the difference between the collagenase activity and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) expression level in normal urethral
      tissue and in urethral scar tissue, and to study the effect of collagenase
      activity and TIMP-1 expression level on the degradation of urethral scar.
      METHODS: The urethral tissues were derived from 10 human surgical specimens of
      urethral stricture scar and 10 human normal urethral specimens from patients with
      brain death. The collagenase activity was detected by ELISA assay, and the TIMP-1
      mRNA level by RTPCR. RESULTS: The collagenase activity of urethral scar tissue
      was (15.32 +/- 2.29) U and lower than that of normal urethral tissue (24.67 +/-
      6.78) U, there was significant difference between them (P < 0.01). The TIMP-1
      expression level of urethral scar tissue was higher than that of normal urethral
      tissue, there was significant difference between them (P < 0.05). CONCLUSION: The
      high level of TIMP-1 expression and the low collagenase activity in urethral scar
      tissue may inhibit the degradation of urethral scar, and may be one of important
      causes of the scar tissue hyperplasia.

PMID- 14663935
TI  - [Expression of connective tissue growth factor gene in the hypertrophic scar and
      keloid tissue].
AB  - OBJECTIVE: To explore the effect of connective tissue growth factor on the
      pathogenesis of hypertrophic scar and keloid tissue. METHODS: The content of
      hydroxyproline was determined and the expression of connective tissue growth
      factor gene was detected by the reverse transcription-polymerase chain reaction
      and image analysis technique in 5 normal skins, 15 hypertrophic scars and 7
      keloid tissues. RESULTS: The contents of hydroxyproline in the hypertrophic scar
      (84.10 +/- 1.76) and keloid tissue (92.38 +/- 2.04) were significantly higher
      than that of normal skin tissue (26.52 +/- 4.10) (P < 0.01). The index of
      connective tissue growth factor mRNA in the hypertrophic scar (0.78 +/- 0.63) and
      keloid tissue (0.84 +/- 0.04) were higher than that of normal skin tissue (0.09
      +/- 0.25) (P < 0.01). CONCLUSION: Connective tissue growth factor may play an
      important role in promoting the fibrotic process of hypertrophic scar and keloid
      tissue.

PMID- 14663936
TI  - [Effect of nandrolone phenylpropionate on expression of hepatic albumin-mRNA and
      androgen receptor in burned rats].
AB  - OBJECTIVE: To study the mechanism of nandrolone phenylpropionate (NP) on hepatic
      albumin mRNA and androgen receptor(AR) in burned rats. METHODS: Thirty-two Wistar
      rats with a deep second-degree cutaneous burn of 20% total body surface area were
      randomly divided into two groups: NP group (experimental group, 5 mg/kg NP) and
      normal saline as control group every other day. The expression copy quantity of
      albumin-mRNA and mean integrated absorbency(mIA) of AR in liver tissue were
      measured by quantitative fluorescent RT-PCR and immunohistochemistry respectively
      on the 4th, 7th, 14th and 21st days of post-burned. RESULTS: The expression
      levels of albumin-mRNA and AR in liver tissue in NP group were much higher than
      those in control group. The albumin-mRNA and AR expression increased
      significantly (P < 0.05) after 7 and 14 days, while the expression had no
      significant difference between NP group and control group on the 4th day. A
      positive correlation occurred between the expression level of albumin-mRNA and
      the quantity of AR in liver tissue(r = 0.936, P < 0.05). CONCLUSION: Nandrolone
      phenylpropionate up-regulated respectively the expression of albumin-mRNA and the
      density of AR in liver tissue.

PMID- 14663937
TI  - [Outcomes of cementless total hip replacement in treatment of osteoarthritis].
AB  - OBJECTIVE: To evaluate the clinical results of cementless total hip replacement
      (THR) in treating osteoarthritis and identifying the factors affecting the
      results. METHODS: From January 1995 to December 1999, 76 patients(85 hips) with
      osteoarthritis of hip joint were treated. These patients were assessed according
      to Harris hip score and X-ray film. The average follow-up time was 49.3 months.
      RESULTS: The average Harris score in the patients was 90.9 points. The excellent
      or good rate was 91.9%(75/85). Pain in the thigh existed in 23 hips(27.5%). The
      femoral osteolysis occurred in 14 hips(16.5%). The radiographical result
      demonstrated femoral loosening in 2 hips. Harris score became lower when the
      femoral component was placed in varus position. CONCLUSION: Cementless THR has
      been applied successfully to treatment of osteoarthritis of hip joint. Pain in
      the thigh may be related to the varus placement of femoral component and femoral
      osteolysis. Femoral osteolysis is one of important factors affecting the long
      term outcomes.

PMID- 14663938
TI  - [Diagnosis and treatment of osteopathic parathyroid adenoma].
AB  - OBJECTIVE: To introduce the advanced diagnostic technologies and share the
      surgical experience of parathyroid adenoma. METHODS: From November 1986 to August
      2000, 9 patients with parathyroid adenoma who underwent operations were analyzed
      retrospectively. Out of them, there were 3 males and 6 females and their ages
      ranged from 12 to 55 years with an average of 32 years. The average disease
      course was 4 years and 9 months. General decreased density of the bone cortex and
      subperiosteum absorption were found in all 9 cases, while multi bone cyst lesion
      in 3 cases; obsolete fracture in 5 cases, including 2 cases of nephrolithiasis.
      Before operation, one child bore claudication and the other 8 patients suffered
      from disability. Serum parathyroid hormone (PTH) level increased markedly in 5
      patients examined (633.87-1,017.40 pmol/L, normal value: 28.50-90.50 pmol/L).
      Radionuclide scan showed that imagings of parathyroid adenoma appeared in 3
      patients. RESULTS: Parathyroid adenoma was resected via neck approach in 7 cases,
      and by way of sternum in the other 2 of the adenomas located in the chest.
      Parathyroid adenoma was diagnosed pathologically in 9 cases. All the 9 patients
      had no relapse during the 2-16 years of follow-up, with apparent relief of
      ostealgia and the normal serum PTH level, and roentgenogram showed fracture
      healing, great alleviation of the osteopathia. CONCLUSION: PTH examination as an
      advanced technique plays an important role in the differential diagnosis of
      hypercalcaemia. Color Doppler and radionuclide scan can locate the lesion. It is
      vital to judge the nature of the lesion by naked eyes, while frozen slices serves
      as a necessity to confirm. Enough parathyroid tissue should to be remained to
      assure normal parathyroid function. The variable number and ectopic possibility
      of parathyroid glands should be considered. Both the short-term and long-term
      surgical outcome of parathyroid adenoma are satisfactory.

PMID- 14663939
TI  - [Repair of bone defect due to tumour resection with self-setting calcium
      phosphate cement in children].
AB  - OBJECTIVE: To study the effect of self-setting calcium phosphate cement (CPC) on
      the repair of local bone defects after resection of cyst in children. METHODS:
      From December 1998 to May 2002, 22 patients with bone defects were repaired with
      CPC. Their ages ranged from 4 to 10 years with an average of 8.3 years. There
      were 11 cases of non-ossifying fibroma, 7 cases of osteoid osteoma, 2 cases of
      bone cyst and 2 cases of fibrous dysplasia. The bone defects are located as the
      following: femur in 14 cases, tibia in 6 cases and humerus in 2 cases. CPC
      spongiosa granules were filled in 11 cases, injectable CPC were filled in 2 bone
      cyst cases. The patients were followed up for 5-48 months, averaged 23.5 months.
      RESULTS: Bone matrix grew well and no recurrence was found. CONCLUSION: The
      method with simple CPC in repairing bone defects is safe, non-toxic, economic and
      convenient in children.

PMID- 14663940
TI  - [Treatment of fracture involved articular surface with absorbable screws and
      rods].
AB  - OBJECTIVE: To investigate the treatment results of fracture involved articular
      surface with absorbable screws and rods. METHODS: From October 1995 to May 2002,
      32 patients with fracture involved articular surface were treated with absorbable
      screws and rods with the materials of SR-PGA and SR-PLLA. Bone traction or
      plaster external fixation were carried out postoperatively. RESULTS: The followed
      up period varied from 3 months to 78 months, with an average of 18.5 months.
      According to the articular function evaluation criteria, the results were
      excellent in 24 patients, good in 6 patients and fair in 2 patients. The
      excellent and good rate was 93.7%. The fractures healed, without dislocation,
      infection and local effusion. CONCLUSION: Internal fixation of absorbable screws
      and rods is a perfect procedure for treating fracture involved articular surface,
      which avoided the pain of taking out internal fixation materials of the second
      operation.

PMID- 14663941
TI  - [Treatment of open fracture by vacuum sealing technique and internal fixation].
AB  - OBJECTIVE: To investigate the effect of vacuum sealing(VS) technique and
      emergency internal fixation on the management of limbs open fracture and soft
      tissue dirty defects. METHODS: Fourteen patients (18 limbs) with open fracture
      and soft tissue dirty defects were treated by the VS technique and internal
      fixation after debridement and 14 patients managed by traditional method as
      control group. Wound surface were covered with polyvinyl alcohol foams with
      embedded drainage tubes connected with vacuum bottle (negative pressure of 50 to
      60 kPa) after wound surface were debrided and fracture were fixed. Wound closure
      was performed with secondary suturing, or free flap, or loco-regional flap and
      mesh-grafts after 5 to 7 days. RESULTS: All wound surface healed completely. No
      complications (systemic and local) were found. After 4-6 months follow-up on
      average, the fracture healed well. There was significant difference in time of
      treatment, total cost of treatment and complication rate between 2 groups (P <
      0.01). CONCLUSION: The VS procedure can drain the wound surface completely,
      decrease infection rate and stimulate the proliferation of granulation tissue. A
      combination of VS with emergency internal fixation is a simple and effective
      method in treatment of limbs open fracture and soft tissue dirty defects.

PMID- 14663942
TI  - [Repair and reconstruction of post-traumatic instability of the ankle].
AB  - OBJECTIVE: To investigate the reparative and reconstructive method of post
      traumatic lateral instability of the ankle. METHODS: From January 1992 to June
      2000, 7 cases of male patients with ankle injury (aged 25-43 years) underwent
      Wetson-Jones modification. A bone tunnel was drilled through 2.5 cm upside the
      lateral malleolus tip and talus, and short peroneal tendon was cut to pass the
      tunnel to fix twining. RESULTS: All patients were followed up 2-10 years, 5 cases
      mineworkers changed to work on the ground, 2 patients returned to the original
      work, no traumatic arthritis occurred. According to Baird ankle joint scoring
      standard, the ankle function was excellent in all cases. CONCLUSION: Reformed
      Wetson-Jones modification can repair and reconstruct perfectly the traumatic
      instability of the ankle.

PMID- 14663943
TI  - [Treatment of lumbar spondylolisthesis with AF device fixation system and
      PROSPACE interbody fusion cage].
AB  - OBJECTIVE: To discuss the clinical effect and the application of AF device
      fixation system and PROSPACE interbody fusion cage on treating lumbar
      spondylolisthesis. METHODS: Twenty-one cases of lumbar spondylolisthesis treated
      by operation from 1999 to 2002 were analyzed retrospectively (13 males and 8
      females, 25-66 years old averaging 42 years). We had thorough decompression on
      the part of nerve compression and had replacement and fixation of the slippage
      vertebral body with the AF transpedicular screw/rod system so that the normal
      spine physiological curvature could be recovered, and then performed the
      posterolateral interbody fusion with implanting the PROSPACE filled with
      autograft bones. RESULTS: All the patients were followed up for 3 months to 3
      years with an average of 15 months. The preoperation symptoms improved in 20
      cases (95.2%). CONCLUSION: The combination of AF device fixation system and
      PROSPACE interbody fusion cage can relieve effectively nerve compression, recover
      the normal spinal physiological curvature, maintain the height of interbody and
      promote the nerve fusion. It is reliable and effective in the treatment of
      spondylolisthesis.

PMID- 14663944
TI  - [Treatment of degenerative lumbar spine instability with transpedical screw
      fixation and intertransverse process autogenous bone grafting].
AB  - OBJECTIVE: To observe the early clinical results with degenerative lumbar
      instability treated with transpedical screw fixation and intertransverse process
      autogenous bone grafting. METHODS: From September 2000 to February 2002, 19
      patients (5 males and 14 females) of degenerative lumbar spine instability were
      treated with decompression for spinal canal stenosis, transpedical screw fixation
      and intertransverse process autogenous bone grafting. The locations of
      degenerative lumbar spine instability were between L4 and L5 in 10 patients,
      between L3, L4 and L5 in 4 cases, between L3 and L4 in 3 cases, between L5 and S1
      in 2 cases. The results were evaluated after operation. The preoperative clinical
      symptoms disappeared completely as excellent results, relieved obviously as good
      results, improved as fair results and unrelieved or worsened as poor results.
      RESULTS: Seventeen patients were followed up for 4-18 months with an average of
      8.1 months. The results of the treatment were excellent in 12 patients, good in 4
      patients and fair in 1 patient. The excellent and good rate was 94.1%.
      Intertransverse process arthrodesis was obtained after 6 months of operation in
      all cases. No loosened and broken instruments occurred. CONCLUSION: The
      advantages of degenerative lumbar spine instability treated with transpedical
      screw fixation and intertransverse are reliable fixation, high successful rate of
      fusion and less influence on spinal canal. The above results show satisfactory
      clinical outcome.

PMID- 14663945
TI  - [Changes of neural electrophysiology properties of cauda equina in experimental
      lumbar spinal canal stenosis under dynamic burden].
AB  - OBJECTIVE: To study the changes of neural electrophysiology properties of cauda
      equina under double level compression and dynamic burdens, and to clarify the
      mechanisms of intermittent neurogenic claudication. METHODS: Thirty SD rats were
      divided into 5 groups (6 in each group). The laminectomy of L5 was performed in
      control group. In the experimental groups, the silicon sheets were inserted into
      the spinal canal of L4 and L6 to cause double level compression of cauda equina
      by 30%. Two hours after onset of compression, no dynamic burden was introduced in
      experimental group 1. Only high frequency stimulation(HFS) was introduced for 6
      minutes in experimental group 2. Both HFS and additional increased compression
      were introduced for 6 minutes in experimental group 3. While only additional
      increased compression was introduced for 6 minutes in experimental group 4. After
      6 minutes of dynamic burdens, all were returned to the status of static
      compression for another 30 minutes and then electrical examination was made.
      RESULTS: After 2 hours of compression, motor and sensory nerve conduction
      velocity (NCV) of all the four experimental groups decreased significantly (P <
      0.05), but there was no significant difference between them. There was no
      significant change in the control group. There was no significant change of NCV
      in experimental group 1 during the last 30 minutes of experiment. NCV in the
      other three experimental groups decreased after introduction of dynamic burdens,
      especially in the experimental group 3. CONCLUSION: The above results showed that
      NCV of cauda equina decreased significantly under dynamic burdens during static
      compression. Two kinds of dynamic burdens introduced at the same time can cause
      more profound change than a single one.

PMID- 14663946
TI  - [Retrospective analysis of 75 cases of flap transplantations in children].
AB  - OBJECTIVE: To investigate the therapeutic effect of flap transplantation in
      repairing soft tissue defects of children. METHODS: From January 1997 to May
      2002, 75 cases of different soft tissue defects (52 males and 23 females, with
      the age of 3-14 years) were repaired by axial and non-axial flaps transfer, and
      axial flaps transplantation by microvascular anastomosis. The flaps area ranged
      from 3 cm x 5 cm to 15 cm x 42 cm. Emergency operation was performed in 26 cases
      and secondary operation in 49 cases (infective wound such as osteomyelitis and
      plate extra-exposed of fracture). The defect regions included the forearm, back
      of the hand, thumb, index finger, leg and foot. The types of flap graft and
      application range included 39 cases of axial flaps transfer or transplantation
      (27 cases of along- or contra-transfer of transplantation and 12 cases of
      microvascular anastomosis). The non-axial flaps transfer were designed along- or
      contra-transfer near the wound area in 36 cases. The ratio of length to width was
      2.5:1-3.5:1 in 27 cases, and larger than 3.5:1 in 9 cases. Adequate anesthesia
      method should be chosen according to the characteristics of children, non
      traumatic operating during surgery and postoperative supervision and nursing of
      flaps should also be paid enough attention. RESULTS: After operation, blood
      circulation crisis occurred in 2 cases (1 case of artery failure and 1 case of
      vein failure). The flaps survived in 37 cases and partially survived in 1 case
      and necrosed in 1 case. The survival rate was 96.2%. The postoperative follow-up
      period was 3 to 60 months, the blood supply, elasticity and texture of flaps were
      good. The effect of repair was satisfactory. CONCLUSION: Different types of
      transplantation of blood-supply of flaps may repair the different types of soft
      tissue defects in children. Free flap transplantation is safe and beneficial in
      children, different defects of soft tissue were repaired by axial and non-axial
      flaps transfer, axial flaps transplantation by microvascular anastomosis. Non
      traumatic operating and postoperative supervision and nursing of flaps should
      also be paid enough attention.

PMID- 14663947
TI  - [Surgical treatment of micromandibular deformity associated with obstructive
      sleep apnea syndrome].
AB  - OBJECTIVE: To study the effects of jaw advancement in treating micromandibular
      deformity associated with obstructive sleep apnea syndrome (OSAS) by ramus
      osteotomy and genioplasty. METHODS: From April 1998 to February 2002, 12 patients
      with micromandibular deformity associated with OSAS (aged 14-36 years, 7 females
      and 5 males) were treated. Invert "L" shape ramus osteotomy and inverted
      replantation of posterior segment of ramus were performed to reconstruct the TMJ
      with the jaw advancement and genioplasty at the same time in 7 cases; mandibular
      angle osteotomy, bone grafts and genioplasty in 3 cases; and the jaw advancement
      by ramus sagittal osteotomy and genioplasty in 2 cases of the first branchial
      arch syndrome. RESULTS: The follow-up period was 6 months to 4 years. All the
      patients gained good appearance and had the distance of opening movement over 3.0
      cm. Micromandible and facial asymmetries were corrected satisfactorily. The ratio
      of SaO2 was ascended from 82%-92% (preoperation) to 97%-99% (postoperation). OSAS
      was relieved. CONCLUSION: The jaw advancement by ramus osteotomy and genioplasty
      for treating micromandibular deformity associated with OSAS can correct the
      maxillofacial deformities and enlarge the upper airway space to relieve OSAS.
      This method has achieved satisfactory result.

PMID- 14663948
TI  - [Application of different flaps in immediate reconstruction of maxillary defect].
AB  - OBJECTIVE: To investigate the method and clinical effect of temporal fascia flap,
      free forearm flap, free iliac bone transfer and immediate implant on
      reconstruction of maxillary defect. METHODS: From February 1999 to July 2002, 8
      cases of maxillary defects due to excision of cancer were repaired immediately
      with temporal fascia flap, free forearm flap, free iliac bone transfer and
      implant. Out of 8 patients, there were 6 males and 2 females, aged 32-49 years,
      with a disease course of 3 months to 2 years. RESULTS: Free iliac bone and
      forearm flap survived in all 8 cases. Osseo-integration could be seen and the
      implants could be used for denture repair and chew function. After 6-12 months, X
      ray examination showed iliac bone healing; facial shape and functional
      restoration were satisfactory. CONCLUSION: Temporal fascia flap, free forearm
      flap, free iliac bone transfer and immediate implant is an ideal method to repair
      maxillary defect immediately and reconstruct its function.

PMID- 14663949
TI  - [Supervision, administration and standard research related to tissue engineered
      medical products].
AB  - Tissue engineering advance in supplying the reparative and reconstructive
      medicine with promising tissue engineered medical products(TEMPs) and the new
      therapy alternative. The related supervision and administration of TEMPs is being
      developed and the standard research of TEMPs is also in progress. The Food and
      Drug Administration(FDA) of the United States has treated TEMPs as combined
      products and supervised them according to the level of risk to patients. Lately,
      FDA has determined that the Center for Devices and Radiological Health (CDRH)
      should take charge of examination and approval of TEMPs, with the cooperation of
      the Center for Biological Evaluations and Research(CBER). The regulatory controls
      have been established respectively in European Union and Japan. In China, TEMPs
      are identified as medical devices combined with cells. The Department of Medical
      Device of the State Food and Drug Administration (SFDA) is responsible for the
      examination and approval of TEMPs, and National Institute for the Control of
      Pharmaceutical & Biological Products(NICPBP) is responsible for evaluation tests.
      The standards of TEMPs are formulated mainly by the American Society of Testing
      Materials(ASTM) and International Standardization Organization(ISO).

PMID- 14663950
TI  - [Repair of upper tibial epiphyseal defect with engineered epiphyseal cartilage in
      rabbits].
AB  - OBJECTIVE: To observe the effect of engineered epiphyseal cartilage regenerated
      in vitro with 3-D scaffold by chondrocytes from epiphyseal plate in repairing the
      tibial epiphyseal defect, and to explore the methods to promote the confluence
      between engineered cartilage and epiphyseal plate. METHODS: Chondrocytes were
      isolated enzymatically from the epiphyseal plates of immature rabbits, and then
      planted into the tissue culture flasks and cultivated. The first passage
      chondrocytes were collected and mixed fully with the self-made liquid biological
      gel at approximately 2.5 x 10(7) cells/ml to form cell-gel fluid. The cell-gel
      fluid was dropped into the porous calcium polyphosphate fiber/poly-L-lactic
      acid(CPPf/PLLA)scaffold, and a cell-gel-scaffold complex formed after being
      solidified. The defect models of 40% upper tibial epiphyseal plate were made in
      72 immature rabbits; they were divided into 4 groups: group A(the cell-gel
      scaffold complex was transplanted into the defect and the gap filled with
      chondrocyte-gel fluid), group B (with noncell CPPf/PLLA scaffold), group C(with
      fat) and group D(with nothing). The changes of roentgenograph, gross and
      histology were investigated after 2, 4, 6, 8, 12 and 16 weeks of operation.
      RESULTS: In group A, the typical histological structure of epiphyseal plate
      derived from the engineered cartilage with a fine integration between host and
      donor tissues after 2 weeks. The repaired epiphyseal plate had normal
      histological structure without deformation of tibia after 4 weeks. The early
      histological change of epiphyseal closure appeared in the repaired area with
      varus and shortening deformation of the tibia after 8 weeks. The epiphyseal plate
      was closed in the repaired area with more evident deformation of tibia; the
      growth function of repaired epiphyseal plate was 43.6% of the normal one. In
      groups B, C and D, deformation of tibia occurred after 2 weeks; the defect area
      of epiphyseal plate was completely closed after 4 weeks. The deformation was very
      severe without growth of the injured epiphyseal plate after 16 weeks, and no
      significant difference was observed between the three groups. CONCLUSION:
      Engineered epiphyseal cartilage can repair the epiphyseal defect in the
      histological structure with partial recovery of the epiphyseal growth capability.
      Injecting the suspension of fluid chondrocyte-gel into the defects induces a fine
      integration of host and donor tissues.

PMID- 14663951
TI  - [Preparation of acellularized porcine heart valve and seeding of bovine aortic
      endothelial cells].
AB  - OBJECTIVE: To explore the possibility of detergent acellularized porcine heart
      valve serving as a scaffold for tissue engineering valve. METHODS: The porcine
      aortic valves were acellularized by use of trypsin-EDTA. Triton X-100, RNase and
      DNase treatment. Biomechanical characteristics of fresh valves and acellularized
      valve were tested; also fresh valves, acellularized valve and valves treated with
      method of bioprothetic treatment were implanted subcutaneously in rats;
      frequently seeded with bovine aortic endothelial cells(BAECs), and then cultured
      for 7 days. RESULTS: The acellularization procedure resulted in complete removal
      of the cellular components while the construction of matrix was maintained. The
      matrix could be successfully seeded with in vitro expanded BAECs, which formed a
      continuous monolayer on the surface. There is no significant difference of PGI2
      secretion of BAECs between cells seeded onto the acellular leaflets and that onto
      the wells of 24-wells plate (P > 0.05). CONCLUSION: Acellularied porcine aortic
      valve can be applied as a scaffold to develop tissue engineering heart valve.

PMID- 14663952
TI  - [Experimental study of xenogeneic heart valve material].
AB  - OBJECTIVE: To explore the possibility of improving the performance of tissue
      engineering valve by means of preendothelialization with cultured human umbilical
      vein endothelial cell(hUVEC) and to develop a new xenogenic bioprosthesis valve
      material. METHODS: The porcine aortic valves treated by use of
      glutaraldehyde(GA), epoxychloropropane(EC), L-glutamic acid(L-GA) and cellular
      extraction(CE) respectively were divided into four groups; group 1(GA), group
      2(EC), group 3(EC + L-GA), and group 4(EC + L-GA + CE). The cultured hUVECs were
      seeded onto the treated porcine aortic valve, then that stuff were examined by
      means of EC VIII factor staining, living cells counting and microscopy. RESULTS:
      The cultured hUVEC could adhere to culturing bottle wall an hour later, and
      propagated to two passages after seven days. The cells increased with serial
      passage at a 7-day interval. But the hUVEC grew slowly when seeded onto the
      treated valve material except group 4. The cells in group 4 covered the surface
      of valve completely seven days later, which could also be seen in group 3 but not
      completely. There was no cell growing in group 1, and only fewer in group 2. The
      living cell in groups 3 and 4 were significantly more than in groups 1 and 2 on
      the 3rd, 7th and 14th days (P < 0.01), meanwhile, the number of cells in group 4
      were also significantly more than that in group 3 (P < 0.05). The covering area
      of cultured cell on the valve material in groups 3 and 4 was significantly larger
      than that in groups 1 and 2. The covering area of cell in group 4 was over 95%,
      and higher than that in group 3(60%-70%). The hUVEC of group 4 arranged in
      pattern of three dimension. So it could resist rising of foreign power from the
      cardiac cavity of high pressure and flowing volume. There was no cell on the
      leaflet surface in group 1, and only a few pinch of cells could be seen in group
      2. CONCLUSION: The porcine aortic valve can be used to be an ideal xenogeneic
      valve scaffold; the scaffold of porcine aortic valve should be treated by use of
      epoxy-chloropropane, L-glutamic acid and cellular extraction, so that a best
      growing environment to the hUVEC would be given; the cultured hUVECs used to be
      source of seed living cell had a boundless prospects; the growing velocity of
      cultured hUVEC was controllable, which facilitated clinical application; and the
      endothelial cells of xenogeneic valve material which grew compactly onto the
      scaffold can resist rising of foreign power from the cardiac cavity itself.

PMID- 14663953
TI  - [Construction of tissue engineering skin containing melanocytes].
AB  - OBJECTIVE: To construct a tissue engineering skin containing melanocytes by
      employing tissue engineering method. METHODS: The keratinocytes, dermal
      fibroblasts and melanocytes were isolated and purified. Then the cells were used
      to construct a tissue engineering skin containing melanocytes. The location of
      melanocytes in the tissue engineering skin were detected by Dopa staining,
      transmission electron microscope (TEM) and S-100 immunohistochemical staining.
      RESULTS: Melanocytes can be detected in the basal layer of the constructed tissue
      engineering skin. The results of TEM showed that the melanocytes were in good
      conditions. CONCLUSION: The artificial skin containing melanocytes was
      successfully constructed in vitro and can be used to repair the full-thickness
      skin defects.

PMID- 14663954
TI  - Numerical investigation of blood flow in the arterial stenosis.
AB  - In the cardiovascular system, altered flow conditions--such as separation, flow
      reversal, and low or oscillatory shear stress areas--are recognized as important
      factors in the development of arterial disease. A detailed understanding of the
      local hemodynamics, of the effects of vascular wall modification on flow
      patterns, and of longterm adaptation of the system to surgical procedures can
      have useful clinical applications. In this context, the availability of effective
      and accurate numerical simulation tools could be a real breakthrough. The two
      dimensional flow over a square-step can be regarded as a two-dimensional stenosis
      model from witch some information on the properties at arterial stenoses can be
      obtained.

PMID- 14663955
TI  - Mathematical modelling for the study of respiratory mechanics.
AB  - The target of this study was the development of mathematical models that best
      describe the behaviour of respiratory parameters. First of all, we studied lung
      volume in relation to time both for normal and maximal inspiration/expiration by
      developing mathematical models. For the construction of these equations the
      exponential model was used. Then we tried to study the flow-volume of a typical
      spirometer curve by dividing it into two parts: the first part reaches the Peak
      Expiratory Flow (PEF) point and the second follows until the volume reaches Vital
      Capacity (VC). For the first part we built an exponential equation; for the
      second part a number of existing prediction equations for the flow in various
      points of VC were used. For the volume-pressure diagram, we built exponential
      equations that describe the volume-pressure relation below Vo (Vo: lung volume
      where pressure is zero). The equations were coupled for expiration and
      inspiration. The modeling of respiratory mechanics led us to the conclusion that
      the developed models could offer new potentials in the description of other
      respiratory parameters as well.

PMID- 14663956
TI  - Smart multisensor kernel.
AB  - We describe in this paper a smart multisensor kernel, given the shape of a
      wriststrap and able to characterise a current physiological state among a number
      of ones resulting from a previous analysis, and to transmit those results using a
      radio link. The main advantage of this product is its adaptability. As examples,
      we describe two applications which are the remote monitoring of elderly people
      and the sleep staging.

PMID- 14663957
TI  - Matched time-frequency filter for ECG signal enhancement.
AB  - A new method for ECG signal enhancement is presented, based on "matched" time
      frequency filtering in the Wigner representation. Performance analysis shows that
      the method is particularly useful for noise removal in clinical ECG.

PMID- 14663958
TI  - Morphofunctional visualization of MR-mammography in virtual reality.
AB  - In view of an increasing use of breast MRI supplementing X-ray mammography, the
      purpose of this study was the development of a method for fast and efficient
      analysis of dynamic MR image series of the female breast. The dynamic image data
      sets were analyzed by tracer kinetic modeling in order to describe the
      physiological processes underlying the contrast enhancement in mathematical terms
      and thus to enable the estimation of functional tissue specific parameters,
      reflecting the status of microcirculation. To display morphological and
      functional tissue information simultaneously, a multidimensional real-time
      visualization system (using 3D-texture mapping) was developed, which enables a
      practical and intuitive human-computer interface in virtual reality.

PMID- 14663959
TI  - Delineation of brain structures from positron emission tomography images with
      deformable models.
AB  - Segmentation of positron emission tomography (PET) images is a difficult task. In
      this study, we propose a new method for delineation of brain structures according
      to the tracer uptake. The method is based on a new deformable model which is
      particularly designed for extracting surfaces automatically from noisy images.
      The automation is achieved by using a global optimization algorithm for
      minimizing the energy of the deformable model. As an example, the coarse cortical
      structure was extracted from FDG PET brain images by delineating first the brain
      surface and then the white matter surface. We have tested the method with the
      image of the brain phantom and images from a small number (N = 17) of FDG brain
      studies. The cortical structure was automatically and reliably found from all the
      images. The proposed method provides new opportunities for automatic and
      repeatable structure extraction applicable for regional quantification of the
      tracer uptake.

PMID- 14663960
TI  - Myocardium structure analysis on echocardiographic images.
AB  - The heart disease is caused by the alterations in the biological tissue of its
      muscles. The myocardium alterations have been analysed and evaluated on
      echocardiographic images. The statistical parameters of the heart texture on the
      defined region of interest present information about the state of myocardium.
      There are hundreds of the texture parameters, which could be used to evaluate the
      heart tissue structure. The goal was to choose the most informative ones by
      applying the statistical analysis techniques. The Fisher statistics has been
      applied for hypothesis testing to define the most informative texture parameters.
      The data for the certain position of a transducer has been compiled for sound and
      heart patients. Two kinds of echocardiographic images (native and hormonic ones)
      have been used for analysis. The most informative texture parameters on
      evaluating changes in myocardium structure proved to be: local mean intensity,
      the form of local histogram, local variance and run-length nomuniformity. The
      statistical analysis was limited to the measurements of the most informative
      position of the transducer from the compiled database.

PMID- 14663961
TI  - Genetic programming in medical diagnosis.
AB  - The paper describes the results obtained for differential diagnostics of
      substantially complex disorders in the acid-base status. Since the first attempts
      of applying the genetic programming to this problem, presented by the authors at
      MIE 2000, proved promising, the investigation has been continued. The goal of the
      present study is to create computer genetic programs which, while taking into
      account a set of laboratory gasometric and electrolyte measurements, would be
      able to assist the diagnostics of acid-base disorders. Seven (7) single acid-base
      disorders, eleven (11) double acid-base disorders and six (6) triple complicated
      disorders with accompanying anion gap alterations are approached in the study. A
      set of simulated laboratory measurements has been prepared, providing 250 results
      for the evaluation of the fitness function of the designed genetic computer
      programs, plus some additional results for testing. The final results are
      presented in the form of a confusion matrix for the testing data, which shows
      that the developed system may be helpful in clinical practice.

PMID- 14663962
TI  - Models of surgical procedures for multimodal image-guided neurosurgery.
AB  - Improvement of image guided surgery systems requires a better anticipation of the
      surgical procedure. This anticipation may be provided by a better understanding
      of surgical procedures and/or the use of information models related to
      neurosurgical procedures. We are introducing a generic model of surgical
      procedures in the context of multimodal image-guided craniotomies. The basic
      principle of the model is to break down the surgical procedure into a sequence of
      steps defining the surgical script. Each step is defined by an action; the model
      assigns to each surgical step a list of image entities extracted from multimodal
      preoperative images (anatomical and/or functional images) which are relevant to
      the performance of that particular step. The model has been built in two phases:
      creation and consolidation. Besides, a planning software prototype based on the
      generic model has been built. The resulting generic model is described by an UML
      class diagram and textual description. Some initial benefits of this approach can
      already be outlined: improvement of multimodal information management,
      enhancement of the preparation and the guidance of the surgical act.

PMID- 14663963
TI  - ECG mapping and imaging of cardiac electrical function.
AB  - Inverse electrocardiography has been developed for several years. By coupling
      electrocardiographic mapping and 3D-time anatomical data, the electrical
      excitation sequence can be imaged completely non-invasively in the human heart.
      In this study, a bidomain theory based surface heart model activation time
      imaging approach was applied to single beat data of atrial and ventricular
      depolarization. For sinus and paced rhythms, the sites of early activation and
      the areas with late activation were estimated with sufficient accuracy. In
      particular for focal arrhythmias, this model-based imaging approach might allow
      the guidance and evaluation of antiarrhythmic interventions, for instance, in
      case of catheter ablation or drug therapy.

PMID- 14663964
TI  - An evaluation of hybrid methods for matching biomedical terminologies: mapping
      the gene ontology to the UMLS.
AB  - Integration of disparate biomedical terminologies is becoming increasingly
      important as links between biological science and clinical medicine grow. Mapping
      concepts in the Gene Ontology (GO) to the UMLS may help further this integration
      and allow for more efficient information exchange among researchers. Using a gold
      standard of GO term--UMLS concept mappings provided by the NCI, we examined the
      performance of various published and combined mapping techniques, in order to
      maximize precision and recall. We found that for the previously published
      techniques precision varied between (0.61-0.95), and recall varied from (0.65
      0.90), whereas for the hybrid techniques, precision varied between (0.66-0.97),
      and recall from (0.59-0.93). Our study reveals the benefits of using mapping
      techniques that incorporate domain knowledge, and provides a basis for future
      approaches to mapping between distinct biomedical vocabularies.

PMID- 14663965
TI  - Improving literature based discovery support by genetic knowledge integration.
AB  - We present an interactive literature based biomedical discovery support system
      (BITOLA). The goal of the system is to discover new, potentially meaningful
      relations between a given starting concept of interest and other concepts, by
      mining the bibliographic database Medline. To make the system more suitable for
      disease candidate gene discovery and to decrease the number of candidate
      relations, we integrate background knowledge about the chromosomal location of
      the starting disease as well as the chromosomal location of the candidate genes
      from resources such as LocusLink, HUGO and OMIM. The BITOLA system can be also
      used as an alternative way of searching the Medline database. The system is
      available at http://www.mf.uni-lj.si/bitola/.

PMID- 14663966
TI  - IMGT, the international ImMunoGeneTics information system, http://imgt.cines.fr:
      the reference in immunoinformatics.
AB  - IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr),
      is a high quality integrated information system specializing in immunoglobulins
      (IG), T cell receptors (TR), major histocompatibility complex (MHC) and related
      proteins of the immune system of human and other vertebrates, created in 1989, by
      the Laboratoire d'ImmunoGenetique Moleculaire (LIGM), at the Universite
      Montpellier II, CNRS, Montpellier, France. IMGT is the global reference in
      immunogenetics and immunoinformatics and provides a common access to standardized
      data which include nucleotide and protein sequences, oligonucleotide primers,
      gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT
      includes three sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB hosted at EBI,
      IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB), one 3D structure database
      (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages ("IMGT Marie
      Paule page") and interactive tools for sequence (IMGT/V-QUEST,
      IMGT/JunctionAnalysis, IMGT/Allele-Align, IMGT/PhyloGene) and genome
      (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView) analysis. IMGT data are expertly
      annotated according to the rules of the IMGT Scientific chart, based on the IMGT
      ONTOLOGY concepts. IMGT tools are particularly useful for the analysis of the IG
      and TR repertoires in physiological normal and pathological situations. IMGT has
      important applications in medical research (repertoire analysis in autoimmune
      diseases, AIDS, leukemias, lymphomas, myelomas), biotechnology related to
      antibody engineering (phage displays, combinatorial libraries) and therapeutic
      approaches (graft, immunotherapy). IMGT is freely available at
      http://imgt.cines.fr.

PMID- 14663967
TI  - BioMeKe: an ontology-based biomedical knowledge extraction system devoted to
      transcriptome analysis.
AB  - Semantic interoperability between knowledge bases in medicine, and knowledge base
      in genomics and molecular biology will lead to advances in fundamental research
      as well as to improved patient care. DNA chips strategy is used for transcriptome
      analysis in order to identify deregulated genes in physio-pathological
      conditions. The objective of the BioMedical Knowledge Extraction project
      (BioMeKe) is to develop a knowledge warehouse in the context of transcriptome
      analysis during liver diseases. Knowledge sources include ontologies, related
      terminologies and annotations linked towards public databases (e.g., SWISSPROT).
      BioMeKe has been developed to have access to information using systematic
      investigation upon a concept, gene, gene products, pathology, or any target
      keyword, and is based on the combination of several relevant resources: UMLS,
      GeneOntology, MeSH supplementary terms, GOA, and HUGO. Current efforts are
      focusing on exploiting this ontology-based Knowledge Extractor, to enrich the
      expression data on genes delivered by a liver specific DNA microarray for better
      assistance of analysis.

PMID- 14663968
TI  - Modeling and implementing a health information provider on the Internet.
AB  - OBJECTIVES: To model and implement a medical web portal providing access to well
      qualified and high-quality information. MATERIAL AND METHODS: The Unified Medical
      Language System (UMLS) knowledge sources of the U.S. National Library of Medicine
      and an Information Sources Catalog (ISC) resulting from the ARIANE project are
      described. The XML technology that allows files transformations by the means of
      XSLT is briefly presented. RESULTS: The design and implementation of software
      modules that exploit knowledge sources, operate the translation of a user's query
      to selected information sources, and wrap obtained results are detailed.
      DISCUSSION: Current implementation and wrapping perspectives are discussed in
      terms of integration and interoperability of health information resources.

PMID- 14663969
TI  - A dynamic Web application within an n-tier architecture: a Multi-Source
      Information System for end-stage renal disease.
AB  - A Multi-Source Information System (MSIS) has been designed for the Renal
      Epidemiology and Information Network (REIN) dedicated to End-Stage Renal Disease.
      Interoperability has been considered at 4 levels: semantics, network, formats and
      contents. An n-tier architecture has been chosen at the network level. It is made
      out of a universal client, a dynamic Web server connected to a production
      database and to a data warehouse. The MSIS is patient-oriented, based on a
      regional organization. Its implementation in the context of a regional
      experimentation is presented with insights on the design and underlying
      technologies. The n-tier architecture is a robust model and flexible enough to
      aggregate multiple information sources and integrate modular developments. The
      data warehouse is dedicated to support health care decision-making.

PMID- 14663970
TI  - A new concept for an integrated Healthcare Access Model.
AB  - The increase of population mobility has been promoting a crescent dispersion of
      patient clinical records in Healthcare Information Systems. In this scenario, it
      is mandatory that new services will be available for healthcare practitioners,
      namely web-based interfaces with strong control access mechanisms providing
      effective authentication and identification of persons, and the establishment of
      new access models to the disperse patient information. This paper proposes and
      describes a Healthcare Access Model that integrates a new set of functionalities
      coping with patient mobility and implements an innovative concept of a virtual
      unique Electronic Patient Record--EPR.

PMID- 14663971
TI  - An open Internet platform to distributed image processing applied to dermoscopy.
AB  - Proprietary systems for dermoscopy images analysis are available to improve the
      diagnosis and follow-up of the pigmented skin lesions. Their performance seems
      comparable with that of a human expert. Progress in computer-aided classification
      of melanocytic lesions depends notably on judicious choices of the algorithms
      dedicated to the extraction of signs from the dermoscopy images and of the method
      which combines these signs to classify the lesions. To allow the researcher's
      community to benefit from their large set of elementary algorithms already
      available for dermoscopy, we set up a system accessible through the Internet
      which: allows the engineers to register their algorithms while preserving their
      secrecy: their programs run on their own server; lets a user to define its own
      sequence of image analysis and to apply it to its images: the system
      automatically calls the appropriate remote programs; makes possible and
      stimulates the synergy of worldwide researchers in order to validate algorithms
      of images analysis best suited to achieve the correct diagnosis and to track the
      malignant melanoma; makes these techniques available to the greatest number of
      users through the Web and thus to support a mass screening; reduces the
      maintenance of the system to the minimum: it requires users only an Internet
      browser and engineers to follow a simple widespread standardised interface for
      distributed programs. Various problems should be addressed: the lack of
      standardisation of images acquisition: algorithms based on relative colours are
      best suited to this system; the copyrights on images and algorithms; charging the
      use of remote computer resources. This system allows for an international
      collaborative work in the fight against the malignant melanoma by offering a
      conceptual and technical platform of teledermoscopy. It is intended to support
      synergy between the engineers and the users implied in the diagnosis and teaching
      of dermoscopy.

PMID- 14663972
TI  - Communication of information in the homecare context.
AB  - Organizing the Homecare with new information technologies is nowadays an
      important challenge. Indeed, some medical evolutions as the improvement of the
      duration of life, the number of chronic diseases and some social evolutions, such
      as the quality of patient life, or economic evolutions, such as the reduction of
      hospitalisation costs, could benefit from homecare. In this paper, we present the
      problem of the communication of information in the homecare context. Some main
      phases have been described that compose the two homecare processes: a logistic
      process and a care process. The communication of information during homecare
      depends on the concerned phases: first, some exchanges of information from
      existing Information System to the Homecare Information System; then, some
      exchanges between the homecare system and the mobile health care actors; and
      then, some mails during the outcome phase. Coordination architecture is briefly
      described, and two different implementations for the communication of information
      during homecare are presented: one is using XML messages to exchange information
      between Information Systems; the other is using mobile tools for communicating
      with mobile actors.

PMID- 14663973
TI  - Pervasive self-care solutions in telecardiology. Typical use cases from the EPI
      MEDICS project.
AB  - In western countries, heart disease is the main cause of premature death. Most of
      cardiac deaths occur out of hospital. Because of a continuously growing elderly
      population, the number of heart attacks is steadily increasing. Symptoms are
      often interpreted incorrectly. Victims do not survive long enough to benefit from
      inhospital treatments. To reduce the time before treatment, the only useful
      diagnostic tool to assess the presence of a cardiac event is the
      electrocardiogram (ECG). Event and transtelephonic ECG recorders are used to
      improve decision-making but require setting up new infrastructures. The pervasive
      solution proposed by the European EPI-MEDICS project is an intelligent Personal
      ECG Monitor for the early detection of cardiac events. It includes part of the
      patient electronic health record (EHR), embeds a web server and decision-making
      techniques, generates different alarm levels and forwards alarm messages to the
      relevant care providers by means of new generation wireless communication. It is
      cost saving, involving care providers only if necessary, without requiring to set
      up specific infrastructures. Healthcare becomes personalized, wearable and
      ubiquitous.

PMID- 14663974
TI  - Law and standards faced to market rules in health information security.
AB  - This paper presents the main differences existing in the elaboration process of
      law and standard and analyses their potential conflicts. It also describes the
      respective force of law and standards in three main areas: legal threat versus
      financial threat, conflict versus cooperation and finally their respective
      position faced to oligarchic power.

PMID- 14663975
TI  - Deduction of principles on long-term conservation of electronically signed
      documents by multi professional analyses.
AB  - Due to actual equalization of qualified electronic signatures with handwritten
      signatures and the legal acknowledgment of the electronic form, the opportunity
      to use electronic patient records instead of classic paper-based ones is given.
      The archiving of medical records over a period of 10 to 30 years represents an
      important factor in medical documentation which has to be assured for
      electronically signed documents as well. The ArchiSig project deduces principles
      on long-term conservation of electronically signed documents and corresponding
      technical components to be realized by the means of multi professional analyses.

PMID- 14663976
TI  - Programming secure mobile agents in healthcare environments using role-based
      permissions.
AB  - The healthcare environment consists of vast amounts of dynamic and unstructured
      information, distributed over a large number of information systems. Mobile agent
      technology is having an ever-growing impact on the delivery of medical
      information. It supports acquiring and manipulating information distributed in a
      large number of information systems. Moreover is suitable for the computer
      untrained medical stuff. But the introduction of mobile agents generates advanced
      threads to the sensitive healthcare information, unless the proper
      countermeasures are taken. By applying the role-based approach to the
      authorization problem, we ease the sharing of information between hospital
      information systems and we reduce the administering part. The different
      initiative of the agent's migration method, results in different methods of
      assigning roles to the agent.

PMID- 14663977
TI  - A study design to measure the outcomes of education in data security issues among
      health care professionals.
AB  - The purpose of this paper is to describe a study design compiled to measure the
      outcomes of education in health care data security issues. Based on previous
      studies the knowledge in data security is not very comprehensive and health care
      professionals feel that they need more education and training in information
      technology, specially in the filed of data security issues.

PMID- 14663978
TI  - Automated spoken dialog system for home care and data acquisition from chronic
      patients.
AB  - Recent advances in automatic speech recognition and related technologies allow
      computers to carry on conversations by telephone. We developed an intelligent
      dialog system that interacts with hypertensive patients to collect data about
      their health status. Patients thus avoid the inconvenience of going for frequent
      visits that monitor some clinical variables they can easily measure at home; the
      physician is facilitated in acquiring and reviewing patient information and
      related risk indicators, which are evaluated from the data according to noted
      guidelines. The system described here is a prototype of future configurable and
      component-based dialog systems, which may allow a new modality for users and
      physicians to access electronic health records.

PMID- 14663979
TI  - How should we evaluate patient access to their own records? An example with
      cancer patients in Scotland.
AB  - Government policy in many European countries now assumes that patients should
      have access to their own medical records. Increasingly such access can be used as
      one method of tailoring a wide range of information to the patient. Process
      evaluation, to ensure that human computer interfaces of such systems are
      appropriate, is needed during their design and implementation. However, studies
      to assess the impact on health outcomes are relatively expensive and time
      consuming so are they worth doing? We are carrying out a randomised trial of
      different types of computer-produced booklet including one based on information
      from the medical record. Four hundred cancer patients in Glasgow Scotland have
      been randomised on three binary variables: (a) whether patients chose the
      information themselves or if it was chosen for them; (b) whether it included
      personal information from their own medical record or not; (c) whether it
      included advice on the management of anxiety. We are investigating two 'levels'
      of outcome: (i) whether booklets are used to help engage and so improve patients'
      social support, and (ii) whether booklets and the level of social support affect
      patients' anxiety. We are also assessing anxiety in the patient's 'significant
      other'. To assess the views of both professionals and patients about the utility
      of our study, we developed a website which described our project and asked for
      users' predictions of our outcomes and their assessment of our method. There was
      no consistent prediction for the results of our stud, suggesting that it will be
      worthwhile to complete the study to inform discussion. The results will influence
      the way we give patients access to their medical records and could influence
      perceptions of its importance compared with other health service activities. Even
      though health service policy is to give patients access to their records we still
      need to assess outcomes in terms of health, and wellbeing both for patients and
      their families.

PMID- 14663980
TI  - An implementation of a virtual patient record using Web services.
AB  - Virtual patient records provide a means for integrated access to patient
      information that may be scattered around different healthcare settings. Within
      the boundaries of a health district providing all levels of care, this concept
      can be implemented in a corporate Intranet environment to support longitudinal
      patient care activities across the participating healthcare providers. In this
      context, a virtual patient record implementation enables autonomous healthcare
      providers to operate in a cooperative working environment and apply continuity of
      care. Workflow and web services technologies provide an appropriate
      infrastructure for satisfying collaboration and coordination requirements by
      integrating heterogeneous healthcare applications and by automatically routing
      the medical information needed to authorized actors in a healthcare process. This
      paper presents a virtual patient record architecture that allows integrating
      geographically dispersed medical information within a health district and
      enhancing collaboration and coordination of authorized workgroups using workflow
      and web services technologies. An implementation of the proposed architecture is
      also presented.

PMID- 14663981
TI  - A calculation method for semi automatic follow up of multiple sclerosis by
      magnetic resonance eco planar perfusion imaging.
AB  - Multiple sclerosis (MS) is one of the most common chronic and disabling
      inflammatory and demyelinating disorders of the central nervous system (CNS).
      Magnetic Resonance Imaging (MRI) allows the observation of pathological changes
      in vivo. It has provided a number of important insights into the spatial-temporal
      evolution of MS pathology in vivo. Conventional MRI with T2-weighted images is
      useful in the assessment of oedema early in the inflammatory stage, tissue
      destruction with demyelination and axonal loss, and gliosis later in the chronic
      stage. Examination by conventional MRI usually requires more than one hour and it
      does not completely reveal rapid dynamic changes in blood flow. Recently
      introduced rapid MRI techniques, MR perfusion imaging and MR diffusion imaging,
      allow measurement of pathophysiological changes at the cellular level with a good
      temporal resolution. Nevertheless, until now there were no adequate analytical
      methods available within the clinical routine to differentiate between types of
      MS lesions using fast perfusion MRI. We present an analytical method capable of
      recognizing, and distinguishing, the status of MS lesions by calculating some
      numerical parameters from the MR perfusion images. The method has been tested on
      14 patients affected by MS with different lesions and the results have been
      compared with those obtained with more expensive conventional MRI examinations.
      The proposed method made it possible to recognize the nature of the MS lesions in
      100% of the examined cases without the need to perform long conventional MRI
      examinations, using instead perfusion MRI eco planar imaging which takes no more
      than two minutes. Moreover, the reduced time also allowed reduction of the
      quantity of contrast medium administered to the patient. Further studies may lead
      to the use of this technique for differential diagnoses in other white matter
      diseases.

PMID- 14663982
TI  - Secure communication and management of clinical and genomic data: the use of
      pseudonymisation as privacy enhancing technique.
AB  - The growing need of managing both clinical and genetic data raises important
      legal and ethical challenges. This article introduces some of the privacy
      protection problems related to genomic medicine and highlights the relevance of
      Trusted Third Parties and of Privacy Enhancing Techniques (PETs) in the context
      of e.g. research. Practical approaches based on two pseudonymisation models, for
      both batch and interactive data collection and exchange, are presented.

PMID- 14663983
TI  - Improving computer security by health smart card.
AB  - The University hospitals of Strasbourg have worked for several years on the
      computer security of the medical data and have of this fact be the first to use
      the Health Care Professional Smart Card (CPS). This new tool must provide
      security to the information processing systems and especially to the medical data
      exchanges between the partners who collaborate to the care of the Beyond the
      purely data-processing aspects of the functions of safety offered by the CPS,
      safety depends above all on the practices on the users, their knowledge
      concerning the legislation, the risks and the stakes, of their adhesion to the
      procedures and protections installations. The aim of this study is to evaluate
      this level of knowledge, the practices and the feelings of the users concerning
      the computer security of the medical data, to check the relevance of the step
      taken, and if required, to try to improve it. The survey by questionnaires
      involved 648 users. The practices of users in terms of data security are clearly
      improved by the implementation of the security server and the use of the CPS
      system, but security breaches due to bad practices are not however completely
      eliminated. That confirms that is illusory to believe that data security is first
      and foremost a technical issue. Technical measures are of course indispensable,
      but the greatest efforts are required after their implementation and consist in
      making the key players [2], i.e. users, aware and responsible. However, it must
      be stressed that the user-friendliness of the security interface has a major
      effect on the results observed. For instance, it is highly probable that the bad
      practices continued or introduced upon the implementation of the security server
      and CPS scheme are due to the complicated nature or functional defects of the
      proposed solution, which must therefore be improved. Besides, this is only the
      pilot phase and card holders can be expected to become more responsible as time
      goes by, along with the gradual national implementation of the CPS project and
      the introduction of new functions using electronic signatures and encryption.

PMID- 14663984
TI  - Web and mobile secure access to a Web based medical system.
AB  - This paper describes the implementation of the Web Based Pneumonia
      Chemotherapeutics (WPCh) a Web-based expert system for chemotherapeutic
      assistantship for nosocomial and community-acquired pneumonia based on different
      types of data. WPCh can be accessed through World Wide Web or a mobile phone
      using the relevant script languages. The core of the paper focuses on the usage
      of security of data and the procedures used to accomplish this task. After the
      log in of the physician, he can take advantage of the various modules of the
      expert system in order to view chemotherapeutics and save the data that he
      prefers. The whole procedure can be followed through the interfaces of wap
      technology.

PMID- 14663985
TI  - Application of PKI in health care--needs, ambitions, prospects.
AB  - Through continual development and considerable investment over the past years,
      Slovenia has established an information infrastructure providing efficient data
      links between all the health care actors. This includes furnishing all the
      citizens and health workers with microprocessor cards--health insurance card and
      health professional card. These tools have significantly simplified different
      procedures in the health care and brought services closer to insured persons. The
      know-how and experiences gathered to day have given rise to vivid discussions of
      further development steps: introduction of new contents on the infrastructure in
      place and technological upgrading, in particular progressive incorporation of the
      PKI concept and thereby integration of card and network solutions to provide an
      efficient and secure communication environment. This paper outlines key
      perspectives of the future developments in this segment. With the volume of
      health care data communications through internet growing steeply, and with the
      paramount importance of patient--doctor trust and confidence, security tools and
      solutions in the health care are a critical need.

PMID- 14663986
TI  - MammoGrid: large-scale distributed mammogram analysis.
AB  - Breast cancer as a medical condition and mammograms as images exhibit many
      dimensions of variability across the population. Similarly, the way diagnostic
      systems are used and maintained by clinicians varies between imaging centres and
      breast screening programmes, and so does the appearance of the mammograms
      generated. A distributed database that reflects the spread of pathologies across
      the population is an invaluable tool for the epidemiologist and the understanding
      of the variation in image acquisition protocols is essential to a radiologist in
      a screening programme. Exploiting emerging grid technology, the aim of the
      MammoGrid [1] project is to develop a Europe-wide database of mammograms that
      will be used to investigate a set of important healthcare applications and to
      explore the potential of the grid to support effective co-working between
      healthcare professionals.

PMID- 14663987
TI  - Mapping care processes within a hospital: a web-based proposal merging enterprise
      modelling and ISO normative principles.
AB  - Today, the economic and regulatory environment are pressuring hospitals and
      healthcare professionals to account for their results and methods of care
      delivery. The evaluation of the quality and the safety of care, the traceability
      of the acts performed and the evaluation of practices are some of the reasons
      underpinning current interest in clinical and hospital information systems. The
      structured collection of users' needs and system requirements is fundamental when
      installing such systems. This stage takes time and is generally misconstrued by
      caregivers and is of limited efficacy to analysis. We used a modelling technique
      designed for manufacturing processes (SADT: Structured Analysis and Design
      Technique). We enhanced the initial model of activity of this method and
      programmed a web-based tool in an object-oriented environment. This tool makes it
      possible to extract the data dictionary from the description of a given process
      and to locate documents (procedures, recommendations, instructions). Aimed at
      structuring needs and storing information provided by teams directly involved
      regarding the workings of an institution (or at least part of it), the process
      mapping approach has an important contribution to make in the analysis of
      clinical information systems.

PMID- 14663988
TI  - The CORAS approach for model-based risk management applied to a telemedicine
      service.
AB  - The CORAS risk management process is based on the Australian standard for risk
      management and aims at improved methodology for precise, unambiguous, and
      efficient risk assessment of security critical systems. CORAS addresses security
      critical systems in general, but places particular emphasis on IT security. For
      CORAS, a system is not just technology, but also the humans interacting with the
      technology and all relevant aspects of the surrounding organisation and society.
      The use of graphical models in CORAS furthers communication between the different
      stakeholders of a risk assessment, and makes it easier for non-technicians to
      take part. Telemedicine services and electronic applications used in the health
      sector have a high demand for security. The medical developers, providers and
      users of such services and systems are important contributors in the risk
      assessment of these services and systems. CORAS has successfully been used to
      involve medical professionals in the model-based risk assessment of a
      telemedicine system called Tele-cardiology in Crete. This paper presents the use
      of the CORAS framework to assess this telemedicine system giving some conclusions
      on the experience gained.

PMID- 14663989
TI  - Robot-based tele-echography: the TER system.
AB  - This paper presents a master-slave robotized system enabling a remote echographic
      diagnosis. The expert holds a virtual probe placed on a haptic device; he moves
      this virtual probe in order to control the motion of the real probe positioned on
      the body of the patient located remotely. The real probe is placed on a
      lightweight and user-friendly slave robot and moved by it. The contact force
      between the probe and the patient is fed back to the operator allowing him to
      have a haptic virtual environment. The aim of this haptic control is to preserve
      the medical expert proprioception in order to the facilitate hand-eye
      coordination necessary to echographic examination. In this paper we present the
      architecture of the system and experimental results.

PMID- 14663990
TI  - Automatic coregistration, segmentation and classification for multimodal
      cytopathology.
AB  - The paper describes the key component of the Multimodal Cell Analysis approach, a
      novel cytologic evaluation method for early cancer detection. The approach is
      based on a repeated staining of a cell smear. The correlation of features and
      data extracted from different stainings, and related to relocated individual
      cells, will yield a dramatic increase of diagnostic reliability. The necessary
      fully automatic preprocessing steps are presented: coregistration of multimodal
      images, segmentation, and classification of cell nuclei. Both efficiency and
      robustness of all steps reached at the current stage of research, are high
      regarding medical image material, and strongly support clinical application.

PMID- 14663991
TI  - A collaborative platform for consensus sessions in pathology over Internet.
AB  - The design of valid databases in pathology faces the problem of diagnostic
      disagreement between pathologists. Organizing consensus sessions between experts
      to reduce the variability is a difficult task. The TRIDEM platform addresses the
      issue to organize consensus sessions in pathology over the Internet. In this
      paper, we present the basis to achieve such collaborative platform. On the one
      hand, the platform integrates the functionalities of the IDEM consensus module
      that alleviates the consensus task by presenting to pathologists preliminary
      computed consensus through ergonomic interfaces (automatic step). On the other
      hand, a set of lightweight interaction tools such as vocal annotations are
      implemented to ease the communication between experts as they discuss a case
      (interactive step). The architecture of the TRIDEM platform is based on a Java
      Server-Page web server that communicate with the ObjectStore PSE/PRO database
      used for the object storage. The HTML pages generated by the web server run Java
      applets to perform the different steps (automatic and interactive) of the
      consensus. The current limitations of the platform is to only handle a
      synchronous process. Moreover, improvements like re-writing the consensus
      workflow with a protocol such as BPML are already forecast.

PMID- 14663992
TI  - Interoperability and medical communication using "patient envelope"-based secure
      messaging.
AB  - The process of transmitting patient medical information between different
      healthcare parties involves harmonizing multiple elements: addresses,
      certificates, patient IDs, communication protocol, message format, and
      documents/EPR to be exchanged. Beyond the work done at the "information structure
      level" within CEN TC251, ISO TC215, HL7 and DICOM, it is necessary to focus on
      the "basic medical communication level." An original approach, based on the
      "Patient Envelope", has been developed and successfully implemented for Oncology.
      The operator of the National "Reseau Sante Social" is now proposing a new "secure
      messaging" service supporting the "Envelope"-based communication. The authors are
      actively involved in standardization organizations' works, including EDI Sante,
      DICOM, IETF, and ISO TC 215. The current "envelope" format is compatible with all
      the e-mail clients. It will evolve to be based on the ebXML envelope, extended
      with a "medical header" containing HL7/EHRCOM Data Types and C-METS/GPICs. This
      document describes the results from a 3-year experience, as well as the different
      steps included in the project.

PMID- 14663993
TI  - A conceptual model for documentation of clinical information in the EHR.
AB  - At a national level in Denmark the development of a Conceptual Model for
      Communication in Electronic Health Records (EHR) has moved towards a two-folded
      structure, i.e. a conceptual model for documentation of clinical information, the
      Clinical Process, and a Reference Information Model. The coupled structure
      derived in the final phase of the development of the Conceptual Model for
      Communication in EHR by the end of year 2001. This was inspired by the in-put and
      collaboration of several parties in the Danish healthcare sector throughout the
      period of development from 1999 to the current version 1.01 of the national
      standard was launched by The National Board of Health in January 2002. The
      modelling of the Clinical Process meets the need for a more clinical
      understanding of how the use of information technology, i.e. EHR, can support the
      work processes of shared-care and continuity of care in hospital settings. The
      Clinical Process as a model for documentation in EHR facilitates the capturing of
      clinical information where it emerges in the clinical work processes. The model
      retains in a logical way the clinical relevant relations between different
      information elements that comply with the concept of problem-oriented
      documentation. A comparison between European Pre-standard CEN/ENV 13606 and the
      Danish Conceptual Model reveals different approaches with regard to the focus of
      modelling the EHR information.

PMID- 14663994
TI  - Modelling and implementing electronic health records in Denmark.
AB  - The Danish Health IT strategy [1] points out that integration between electronic
      health records (EHR) systems has a high priority. A prerequisite for real
      integration and semantic interoperability is agreement of the data content and
      the information models. The National Board of Health is working on a common model
      for EHR, but it is not yet fully developed. At the same time several development
      and implementation projects are taking place at a regional level. These EHRs are
      built on information models from different vendors and are based on different
      integration platforms. The Danish EHR observatory, which has been monitoring the
      development of EHRs in Denmark since 1998, have analysed the challenges of using
      different information models and integration platforms. This paper also reports
      new tendencies in modelling and integration platforms globally and how this is
      reflected in the National development.

PMID- 14663995
TI  - Privilege management and access control in Shared Care IS and EHR.
AB  - Realising the shared care concept based on distributed health information
      systems, we have to meet the challenge for advanced security and privacy based on
      a Public Key Infrastructure (PKI) Beside strong authentication, authorisation of
      principals and access control using role concepts and security object
      classification schemes are essential application security services. The paper
      presents the actual drafts of ISO and CEN standards dealing with privilege
      management and access control.

PMID- 14663996
TI  - The impact of EHR and digital electrocardiograms.
AB  - The diffusion of the Electronic Health Record demands seamless integration and
      interoperability of medical devices with 3-party information systems. Nowadays
      cardiovascular diseases are the largest cause of mortality in western countries
      so, especially in the domain of Cardiology, medical devices are an essential part
      in the process of acquiring, storing and communicating accurately the current
      health status of a citizen. The Danish Centre for Health Telematics is
      participating in the European Funded project OpenECG that will assist and support
      manufacturers and integrators in creating interoperable equipment and software
      for seamless exchange of electrocardiograms. A pilot project will be established
      in the Funen Health Care Network to assess the benefits of the electronic
      communication of electrocardiograms.

PMID- 14663997
TI  - Analysis of hospitalised patient flows using data-mining.
AB  - Face to the development of hospital information system in the "Hopital Europeen
      George Pompidou" (HEGP), computerized patients records made medical data easier
      to analyse than before. We use data-mining technology to analyse intra-hospital
      patients' paths with one year of PMSI data (a French medical information system
      similar to Diagnosis Related Group). METHODS: 1. "sequential patterns mining" was
      used to analyse the most frequent patients' paths, 2. an integrated framework of
      "association rules mining" and "classification rule mining" was used to build
      prediction rules of patients' paths. RESULT: We construct a rule based prediction
      model, which gives the tendency of the patient's paths between the different
      medical units.

PMID- 14663998
TI  - A preprocessing method for improving data mining techniques. Application to a
      large medical diabetes database.
AB  - The Knowledge Discovery in Databases (KDD) methodology seems to be attractive on
      the analyze of large clinical databases. In the KDD process, the preprocessing
      step (data cleaning and handling of missing values) is paramount since it
      conditions the quality of the results obtained by data mining procedures and
      represents about 80% of the whole project time. The aims of the present study
      were to analyze this step and provide tools to handle inconsistent data and
      missing values. We have broken down the process into 3 main stages: data cleaning
      -explanatory study of missing values--choice of the procedure used for handling
      missing values. The data cleaning stage was based on a system of logical rules to
      correct mistakes and on cluster analysis to discard the poorly filled files. The
      missing-data mechanism was analyzed by means of multivariate statistical
      procedures. Two methods to deal with missing values were compared: imputation by
      the most common value (mode) and imputation using decision trees. This study was
      performed on a large medical diabetes database (23,601 patients) including
      numerous missing values. A system of logical rules allowed to correct mistakes on
      essential parameters (for example, the type of diabetes). Cluster analysis
      allowed to identify 10% of poorly filled files. After multivariate analysis, the
      missing-data mechanism could be considered as random. For variables with low
      number of missing values (< 10%) and categories (< 4), imputation using decision
      trees provided better results than imputation by mode.

PMID- 14663999
TI  - A methodology for multi-source Record Linkage.
AB  - As patient's medical data is disseminated in different health structures,
      building a data-warehousing system at a regional level, for healthcare co
      operation, has some specific requirements compared to intra healthcare structure
      data-warehousing projects. In particular, there is no common patient electronic
      record's identifier among all the sources. Hence, data integration and Record
      Linkage is the most important issue in such projects. In this paper, we present
      Background on Information integration with the two main approaches of the
      problem: Schema Integration approach and Entity reconciliation approach. We show
      the limits of each of the two approaches and propose an approach based on theory
      of a set partitioning and instance identification.

PMID- 14664000
TI  - How to identify and assess tasks and challenges of Medical Image Processing.
AB  - Research in Medical Image Processing (MIP) is mainly driven by a technology
      oriented point of view. However, as an application-oriented field, MIP research
      should always be able to give an answer to the question of what is the potential
      benefit of a solved MIP problem or a newly developed MIP-based system supporting
      a diagnostic or therapeutic process, in terms of outcome criteria like e.g.
      Quality Adjusted Life Years (QALYs) for the patient or cost savings in health
      care. As one subtask of establishing a Reference Image Database for MIP R&D
      Groups, the Working Group on Medical Image Processing of the European Federation
      for Medical Informatics (EFMI WG MIP) works on an answer. This paper presents the
      concept and the strategy of how the Most Relevant MIP problems (MRMIP) shall be
      identified and assessed in the context of improving evaluation of MIP solutions.

PMID- 14664001
TI  - Image integrity verification in medical information systems.
AB  - In nowadays it is a major objective to protect healthcare information against
      unauthorized access. Comparing conventional and electronic management of medical
      images the later one demands much more complex security measures. We propose a
      new scenario for watermark data buildup and embedding which is independent from
      the applied watermarking technology. In our proposed method the embedded
      watermark data is dependant on image and patient information too. The proposed
      watermark buildup method provides watermark information where it is small in size
      and represents a unique digest of the image and image related data. The embedded
      data can be considered unique with high probability even if the same algorithm
      was used in different medical information systems. Described procedures ensure
      new, more secure links between image and related data, offering further
      perspectives in smartcard implementations.

PMID- 14664002
TI  - DicoSE--a Web-interface based on XML for visualizing and searching the topology
      of the data structure defined by the DICOM 3 standard.
AB  - To adequately visualize and interpret the data fields of DICOM 3 datasets the
      data structure defined in the DICOM 3 standard has to be applied. The DICOM 3
      data structure is very extensive and therefore costly to implement. We are
      working on an open source system which provides the data structure via a Java
      programming interface. The data is held in a freely available XML-database. As a
      spin-off we are providing the web-based Dicom Search Engine (DicoSE) which will
      be available via internet soon. DicoSE allows for searching the DICOM standard
      data dictionary for defined data fields and visualizes the topology of the data
      which is present in DICOM datasets acquired by various types of modalities. Thus,
      the interpretation of the meaning of data fields is supported. For maintaining
      the data stored in the database a web-based administration interface is provided.

PMID- 14664003
TI  - Novel neuroradiological image processing and information retrieval in a
      telestroke system.
AB  - A Cellular Neural Network based image processing system and a system based on
      Interaction Information Retrieval which are basic elements of a stroke
      teleconsultation system with most recent applications are introduced in this
      paper. Both of them are novel approaches in the image processing and information
      retrieval fields.

PMID- 14664004
TI  - Specification levels and collaborative definition for the integration of health
      information systems.
AB  - In this paper, we extend our previous work for defining interoperability for
      health information systems into proposed documentation levels for specifying
      integration, and a model for defining various interoperability aspects in
      collaboration between integrators, health service providers and system providers.
      We are using these models in defining solutions for a set of different
      integration needs in PlugIT project in Finland. We propose collaborative
      definition and clear levels of integration specifications to promote adequacy,
      consistency and efficiency of integration solutions and software component
      specifications in health information systems.

PMID- 14664005
TI  - Beds Simulator 1.0: a software for the modelisation of the number of beds
      required for a hospital department.
AB  - The determination of the number of beds needed for a hospital department is a
      complex problem that try to take into account efficiency, forecasting of needs,
      appropriateness of stays. Health authority used methods based on ratios that do
      not take into account local specificities and use rather to support an economic
      decision. On the other side, the models developed are too specific to be applied
      to all type of hospital department. Moreover, all the solutions depend on the LoS
      (Length of Stay). We have developed a non parametric method to solve this
      problem. This modelisation was successfully tested in teaching and non teaching
      hospitals, for an Intensive Care Unit, two Internal Medicine and a surgical
      departments. A software easy to use was developed, working on Windows available
      on our website www.sante.univ-nantes.fr/med/stat/.

PMID- 14664006
TI  - Electronic signatures for long-lasting storage purposes in electronic archives.
AB  - Communication and co-operation in healthcare and welfare requires certain Trusted
      Third Party (TTP) services describing both status and relation of communicating
      principals as well as their corresponding keys and attributes. Additional TTP
      services are needed to provide trustworthy information about dynamic issues of
      communication and co-operation such as time and location of processes, workflow
      relations, and system behaviour. Electronic signatures based on asymmetric
      cryptography are important means for securing the integrity of a message or file
      as well as for accountability purposes including non-repudication of both origin
      and receipt. These electronic signatures along with certified time stamps are
      especially important for electronic health records (EHR), electronic archives in
      general, and other typical purposes of a long-lasting storage. Apart from
      technical storage problems (e.g. lifetime of the storage devices), this paper
      needs to look for mechanisms of e.g. re-signing of messages, archive details, or
      whole archives.

PMID- 14664007
TI  - Enabling virtual emergency healthcare enterprises using Web services.
AB  - Emergency healthcare delivery involves a variety of activities performed from the
      time of a call to the ambulance service till the time of patient's disposal from
      the emergency department of a hospital. As these activities are performed in at
      least two organizations (i.e. ambulance service and hospital) and they are
      interrelated to form inter-organizational healthcare processes, collaboration and
      coordination become a vital issue for patients and for emergency healthcare
      service performance. Web-based workflow systems in conjunction with web services
      present a new way for service-oriented integration (SOI) of disparate systems and
      for developing distributed applications within and between organizations. Thus,
      through process automation and the use of web services ambulance service and
      hospital emergency departments can automate their operations by making
      information available where and when needed and by providing an infrastructure
      for the integration of pre-hospital and in-hospital emergency healthcare. A
      prototype implementation of this approach is presented in this paper.

PMID- 14664008
TI  - Pragmatic objects modeling environment for Electronic Health Records Systems.
AB  - Customizable shared Electronic Health Care Records require new mechanisms to
      dynamically generate user defined objects. An object model based on a semantic
      network of concepts has been implemented (pragmatic database model). This model
      offers an easier way to represent "archetypes" of user objects including the
      concepts, their relationships and the specific organization and representation of
      the associated knowledge that are necessary to model the context of production of
      record elements. The aim of this paper is the presentation of this framework and
      its implementation in an online electronic health record system using Java Web
      Services technologies. A web-based registry on tobacco was implemented according
      to this framework and is today daily used in 150 tobacco addiction centers.

PMID- 14664009
TI  - The new navigation in EHRs: enabling teamwork of professionals and patients.
AB  - After development of a state of the art electronic health record, which is
      accessible via the internet and belongs to a patient, who can manage access to
      it, the methods of introducing it into routine use in the environment of
      children's oncology is the theme of this paper. The new navigation in an EHR
      intends a shared use for the patient, relatives, and different HCPs. The
      laboratory devices were equipped with an HL7-interface to send messages to the
      HIS. These messages are combined in documents according to the CDA and sent to
      the EHR. In a similar way referral letters are uploaded directly from the HIS.
      Several information resources are used to enlighten the patient and help to
      enable him to become a member of a team for collaborative care. The varying roles
      of patient and HCPs lead to some very interesting questions, which have to be
      answered by a following study.

PMID- 14664010
TI  - The PropeR way to support medical doctors in daily practice. Developing the
      protocol based DSS.
AB  - This paper describes the first phase of the development of a Protocol based
      Decision Support System (PDSS) that will be linked to an Electronic Patient
      Record system (EPR system). The protocol system will be pro-active: the physician
      will be automatically prompted from the EPR of a particular patient if the
      protocol that applies for that patient defines it necessary. The PropeR project
      studies the impact of a PDSS that is linked to an EPR on daily care processes.
      There are two areas of research: hospital and home care. This paper describes the
      application in the hospital. The protocol that is being computerized is a
      treatment protocol for Acute Myelogenous Leukaemia (AML) that also studies
      treatment alternatives (conventional versus experimental treatment). This paper
      based AML protocol has been translated into a formal representation. The KA-tool
      Gaston is used to make this representation. Twenty-eight subprotocols have been
      organized in a hierarchical structure with three levels. One of the aims of the
      project is to make a representation of the AML protocol that can be used in other
      organizations as well. The main problem we encountered is that the representation
      not only contains the content of the protocol, but also aspects of application of
      that protocol in daily care of the hospital and aspects of support. The solution
      to this problem is the creation of two layers of representation: the first layer
      is an exact copy of the protocol and thus sharable and the second layer focuses
      on the support of the protocol in the daily working processes and is mainly
      domain specific: for the University Hospital Maastricht. At the moment, this
      division into two layers is being discussed.

PMID- 14664011
TI  - PropeR revisited.
AB  - The PropeR EHR is a multidisciplinary EHR system that is built using existing
      open source components. This paper discusses the implementation of this system
      and the advantages and challenges encountered when using open source components.

PMID- 14664012
TI  - Body surface potential mapping--the application in men from the twenty years
      lasting epidemiological study.
AB  - Body surface potential mapping (BSPM) enables to obtain more information about
      local changes of the heart electrical field then classical electrocardiography
      makes it possible. We performed this non-invasive diagnostic method in the group
      of 108 men in the frame of the primary preventive study of the risk factors of
      atherosclerosis. The findings of BSPM were compared to the selective coronary
      angiography. The study was started in the years 1976-1979 in the district Prague
      2. Out of 2370 invited middle-aged men, 1419 took part in the study. 937 men
      (66.0%) were affected by one or more risk factors of atherosclerosis. No
      statistical significance was found in regard to the number and the level of risk
      factors of atherosclerosis between the groups of patients with different findings
      on the coronary angiography. Nevertheless, the method of BSPM is a very useful in
      epidemiological studies of atherosclerosis, namely with coronary localization, in
      clinical practice, and in the biomedical research too.

PMID- 14664013
TI  - Criteria for classification of medical information.
AB  - Medical information, which is the central notion in medical informatics, covers a
      large scale of structures and forms. Several classifications are possible and two
      criteria have been used in this paper: structural level and informational level.
      According to structural level we can distinguish three major areas:
      bioinformatics and neuroinformatics for molecular/cellular level, medical
      informatics for individual level and health informatics for community level and
      healthcare units. According to informational level the terms of data and
      knowledge are used and the representative information for each structural level
      is analysed also from this point of view: Finally, information transfer from
      living systems to computers is also seen through the structural point of view.

PMID- 14664014
TI  - Information system interoperability in a regional health care system
      infrastructure: a pilot study using health care information standards.
AB  - The 1st and 2nd Regional Health Care System Authority of Central Macedonia (1st
      and 2nd PeSY) are two of the seventeen Regional Healthcare System Authorities in
      Greece. Every single PeSY aims to improve the level of quality that health care
      organisations offer as well as to control the expenditure of health care services
      provided by the health care organisations, Hospitals and Primary Care Health
      units. There is currently an urgent need for Regional Health Authorities to
      deploy integrated healthcare information system, based on secure networks. The
      limited interoperability of current hospital information systems (HIS) poses a
      risk for the management of patient related information since there is a
      difficulty to transform processed data into useful information and knowledge.
      Thus, a pilot system was developed to achieve data integration record
      synchronisation using the Health Level 7 protocol between the existing HIS of two
      Hospitals of Thessaloniki and the central Offices of the PeSY. The pilot was
      funded by the Third Community Support Framework (jointly funded by EU and Greece)
      funds in order to prepare the forthcoming major healthcare IT projects in Greece.
      It is shown that such a system is pragmatic, achieves data integration and
      provides acceptable integration costs.

PMID- 14664015
TI  - Using discharge letters and context representation in information retrieval of
      medical literature.
AB  - Electronic discharge letters are in many cases insufficient as a recipe for
      further treatment and recovery. Through using discharge letters as input to our
      neural network based information retrieval system Pasent, we have been able to
      provide relevant medical information. The Pasent search method uses predefined
      knowledge about the context, paired with the vocabulary of the input document, to
      compute a relevance measure for a potential result document. In the reported
      experiments, we achieved search results comparable to the tftdf method without
      building specialised context models for the experiment.

PMID- 14664017
TI  - New terminology services based on term comparison using semantic definitions and
      similarity computation.
AB  - As medical information can be encoded within different terminological systems,
      terms comparison is an important issue to allow communication between
      applications. In description logics, terms are compared by the means of semantic
      definitions and subsumption relations. Similarity is also a convenient method for
      term comparison but is not supported by terminology servers which implement
      subsumption relations. We present new terminology services built on a semantic
      distance that could help for semantic mediation between medical applications
      ranging from semi-automatic encoders to data mining tools. These services are 1)
      comparison between terms 2) k-nearest-neighbors 3) support for concept coding 4)
      automatic generation of similarity tables 5) distance based queries 6) support
      for clustering.

PMID- 14664016
TI  - Evaluation of WordNet as a source of lay knowledge for molecular biology and
      genetic diseases: a feasibility study.
AB  - OBJECTIVES: While several sources of biomedical knowledge are available, these
      resources are often highly specialized and usually not suitable for a lay
      audience. This paper evaluates whether concepts needed for molecular biology and
      genetic diseases are present in WordNet, the electronic lexical database.
      METHODS: Terms for four broad categories of concepts (phenotype, molecular
      function, biological process, and cellular component) were extracted from
      LocusLink and mapped to WordNet. All terms from the Gene Ontology database (gene
      products and ontology concepts) were also mapped to WordNet in order to evaluate
      its global coverage of the domain. Additionally, we tested two methods for
      improving the mapping of genetic disease names to WordNet. RESULTS: The coverage
      of concepts ranged from 0% (gene product symbols) to 2.8% (cellular components).
      Removing specialization markers from the terms and using synonyms significantly
      increased the rate of mapping of genetic disease names to WordNet. CONCLUSIONS:
      Many of the most common single gene disorders are present in WordNet, as well as
      many high-level concepts in Gene Ontology. Therefore, WordNet is likely to be a
      useful source of lay knowledge in the framework of a consumer health information
      system on genetic diseases.

PMID- 14664018
TI  - Using cross-lingual information to cope with underspecification in formal
      ontologies.
AB  - Description logics and other formal devices are frequently used as means for
      preventing or detecting mistakes in ontologies. Some of these devices are also
      capable of inferring the existence of inter-concept relationships that have not
      been explicity entered into an ontology. A prerequisite, however, is that this
      information can be derived from those formal definitions of concepts and
      relationships which are included within the ontology. In this paper, we present a
      novel algorithm that is able to suggest relationships among existing concepts in
      a formal ontology that are not derivable from such formal definitions. The
      algorithm exploits cross-lingual information that is implicity present in the
      collection of terms used in various languages to denote the concepts and
      relationships at tissue. By using a specific experimental design, we are able to
      quantify the impact of cross-lingual information in coping with
      underspecification in formal ontologies.

PMID- 14664019
TI  - The effect of a general lexicon in corpus-based identification of French-English
      medical word translations.
AB  - We present a method, based on the similarity of word distribution across
      languages, of finding 'new' words' translations in French-English comparable
      medical texts, starting from a partial bilingual medical lexicon. In this paper,
      we test the influence of adding general-language words to this initial lexicon.
      Our experimental results show that all test words are correctly translated within
      the top 25 candidates; and that the addition of general words to the lexicon
      helps to improve translation accuracy for medical words.

PMID- 14664020
TI  - Modelling dependencies between relations to ensure consistency of a cerebral
      cortex anatomy knowledge base.
AB  - A symbolic model of anatomy that could be used in various contexts is a key
      feature. However, explicitly representing anatomy requires managing many
      specialisation, part-whole and topological relationships. Furthermore, we notice
      dependencies between some of them. These dependencies have to be taken into
      account in order to insure both intrinsic and incremental consistency of the
      model. Our approach is composed of three steps. First, we define the
      relationships between anatomical concepts by relationships between the space
      region they take up or the portion of matter they are made of. Second, we use
      these definitions and properties of spatial and matter relationships to infer
      dependencies between anatomical relationships. Eventually, we apply these
      dependencies to the set of independent anatomical relationships to automatically
      generate all the dependent relationships. This method was used to maintain an
      anatomical model of the frontal, temporal, parietal and occipital regions of the
      cerebral cortex. For 113 concepts, 221 of the 370 relationships could be
      automatically generated. The more the number of concepts increase, the more
      pertinent the method appears.

PMID- 14664021
TI  - A novel view on information content of concepts in extremely large ontologies.
AB  - Semantic distance and semantic similarity are two important information retrieval
      measures used in word sense disambiguation as well as for the assessment of how
      relevant concepts are with respect to the documents in which they are found. A
      variety of calculation methods have been proposed in the literature, whereby
      methods taking into account the information content of an individual concept
      outperform those that don't. In this paper, we present a novel recursive approach
      to calculate a concept's information content based on the information content of
      the concepts to which it relates. The method is applicable to extremely large
      ontologies containing several million concepts and relationships amongst them. It
      is shown that a concept's information content as calculated by this method
      provides additional information with respect to an ontology that cannot be
      approximated by hierarchical edge-counting or human insight. In addition, it is
      suggested that the method can be used for quality control within large
      ontologies.

PMID- 14664022
TI  - Towards a unified medical lexicon for French.
AB  - Medical Informatics has a constant need for basic Medical Language Processing
      tasks, e.g., for coding into controlled vocabularies, free text indexing and
      information retrieval. Most of these tasks involve term matching and rely on
      lexical resources: lists of words with attached information, including inflected
      forms and derived words, etc. Such resources are publicly available for the
      English language with the UMLS Specialist Lexicon, but not in other languages.
      For the French language, several teams have worked on the subject and built local
      lexical resources. The goal of the present work is to pool and unify these
      resources and to add extensively to them by exploiting medical terminologies and
      corpora, resulting in a unified medical lexicon for French (UMLF). This paper
      exposes the issues raised by such an objective, describes the methods on which
      the project relies and illustrates them with experimental results.

PMID- 14664023
TI  - A probabilistic information retrieval approach to medical annotation in SWISS
      PROT.
AB  - The goal of medical annotation of human proteins in Swiss-Prot is to add features
      specifically intended for researchers working on genetic diseases and
      polymorphisms. For this purpose, it is necessary to search through a vast number
      of publications containing relevant information. Promising results have been
      obtained by applying natural language processing and machine learning techniques
      to solve this problem. By using the Probabilistic Latent Categorizer on
      representative query sets, 69% recall and 59% precision was achieved for relevant
      documents. This classifier also rejected irrelevant abstracts with more than 96%
      precision. Better linguistic pre-processing of source documents can further
      improve such computer approach.

PMID- 14664024
TI  - Data representation in healthcare: a design for a freely-available openly
      developed international reference terminology for healthcare.
AB  - The importance of data representation in healthcare has been of concern for
      centuries. In the last fifty years there has been an increasing awareness of the
      need for formal representations of terminological systems. We propose that
      terminological system development should be consensus driven and the product of
      iterative open refinement in order to practically serve the needs of the
      healthcare community. The system of development and maintenance of such a system
      must involve recruitment of the best and the brightest in the medical community
      to take responsibility for insuring the accuracy and completeness of such an
      effort. We suggest a method for algorithmically building a starting point for
      such a reference terminology. Further we suggest a distributed authoring
      environment that would allow domain experts to contribute regardless of their
      location or language. Open intellectual contribution is the necessary ingredient
      for a consensus based international health reference terminology.

PMID- 14664025
TI  - A frame-based representation of ICD-10.
AB  - Physicians are required to code information concerning a patient's stay in order
      to measure the medical activity in hospitals. They use the International
      Statistical Classification of Diseases and Related Health Problems, Tenth
      Revision (ICD-10). Coding is usually performed manually and computerized tools
      may be useful in speeding up and facilitating the tedious task of coding patient
      information. The aim of this work is to build a surface semantic model of ICD-10
      in order to ameliorate a coding help system. METHODS: This work was focused on
      chapter XI of the ICD-10, Diseases of the Digestive System. Each term from both
      analytical and alphabetical indexes about this chapter were submitted to a
      morphological analysis in order to extract the medical concepts within. After a
      statistical analysis of these concepts and the way they connect themselves, a
      semantic model based on a "semantic frame" approach was built. RESULTS: Although
      this model could represent a reasonable amount of medical knowledge within
      chapter XI of the ICD-10 in a quite satisfactory way, it shows lack of efficiency
      for some other chapters. CONCLUSION: Difficulties have to be overcome when
      modelling a classification meant for manual utilisation, and a lot of work still
      has to be done to obtain an effective coding help system using the ICD-10.

PMID- 14664026
TI  - Re-use of a multi-purpose knowledge corpus on cortex anatomy for educational
      purposes.
AB  - This work aims at producing a software package to be used during "hands on"
      sessions about anatomy, focusing on gross brain cortex anatomy. Emphasis is put
      on the 3D shape and topology of the cortex anatomical structures, described both
      using numeric data (derived from MRI images) and symbolic data ("part-whole",
      topological realtions). "Spatial" and "semantic" synchronisation are provided to
      connect the numeric and symbolic knowledge. The knowledge corpus includes both 3D
      data showing the sulci, the gyri and the 3D MRI data, and a general purpose
      symbolic knowledge base of brain cortex anatomical features. Implementation is
      achieved using web technologies.

PMID- 14664027
TI  - Matching controlled vocabulary words.
AB  - This study examines an enabling condition for natural languages access to medical
      knowledge resources (Medline, CISMeF) indexed with controlled vocabularies (e.g.,
      the MeSH): is the vocabulary of user queries comparable with that of the index
      terms? The two vocabularies were compared in their original form, then under
      incrementally normalized forms, using character-based normalizations then
      linguistic normalizations. Only 16.7% of the user vocabulary, in its original
      form, is in the MeSH. Progressive normalizations increase this proportion to
      65.5%. Besides, if the frequencies of occurrence of words are taken into account,
      89.3% of user word occurrences can be matched to MeSH words. This shows the
      interest of taking into account further matching methods between queries and
      index terms than those presented here.

PMID- 14664028
TI  - Knowledge representation in digital medical documents for efficient information
      access and retrieval.
AB  - Information access and retrieval are essential to serve the delivery and
      application of evidence-based medicine. The literature provides evidence for the
      effectiveness of computerization of medical knowledge for increasing compliance
      with current standards and improving patient outcomes. But all efforts in
      implementing knowledge-based functions remain limited in respect of either the
      prolonged exposure to live clinical use, the complexity of knowledge content
      supported, the dependencies on a technology platform and host system, or the
      proof of use and content sharing across multiple and varying environments. We
      have to face currently an information overload, especially in medicine. As a
      result, efficient ways of implementation of evidence-based care become more and
      more important. Most of the medical knowledge contained in textbooks, guidelines,
      journals as well as online resources is text-based. In order to present problem
      specific information at the point of care the outlined concept relies on a
      document-based solution with the eXtensible Markup Language (XML). The adoption
      of XML as a standard for the publication and interchange of documents creates a
      great opportunity for better information retrieval. On the basis of structured
      data we are able to improve the search quality for clinical information which
      forms a crucial pre-requisite for the implementation of evidence-based care.

PMID- 14664029
TI  - A contextual coding system for transplantation and end stage diseases.
AB  - The Establissement francais des Greffes (EfG) is a state agency dealing with
      Public Health issues related to organ, tissue and cell transplantation in France.
      EfG maintains a national information system (EfG-IS) for the evaluation of organ
      transplantation activities. The EfG-IS is moving toward a new n-tier architecture
      comprising a terminological server. Because this terminological server is shared
      by various kind of transplant teams and dialysis centers to record patients data
      at different time point, contextualisation of terms appeared as a functional
      requirement. We report in this paper various contexts for medical terms and how
      they have been taken into account.

PMID- 14664030
TI  - Towards a medical question-answering system: a feasibility study.
AB  - Question-answering (QA) systems, as have been presented and evaluated in several
      TREC conferences, are the next generation of search engines. They combine
      'traditional' Information Retrieval (IR) with Natural Language Processing (NLP)
      and Knowledge Engineering techniques to provide shorter, more precise answers to
      natural language questions. We study here the feasibility of such a system for
      French in the health care domain. In this purpose, we collected a corpus of
      student questions in oral surgery. We examined two enabling conditions: on the IR
      side, how to select the right keywords in a question to identify relevant
      material on the Web for answering this question, a prerequisite for success; and
      on the NLP side, whether the contents of the questions fit the conceptual model
      of an existing QA prototype, a favorable condition for rapid implementation. A
      manual Web search enabled us to devise automatable principles for building IR
      queries for these questions. Besides, we could design a semantic model, using
      UMLS Semantic Network relations, which is consistent with our prototype and
      covers 90% of the questions. However, the high specialization of the domain and
      the clinical orientation of the questions, joined with the more limited resources
      online in the French language, may restrain the quantity of Web material
      available for answering these questions.

PMID- 14664031
TI  - Relating UMLS semantic types and task-based ontology to computer-interpretable
      clinical practice guidelines.
AB  - Medical knowledge in clinical practice guideline (GL) texts is the source of task
      based computer-interpretable clinical guideline models (CIGMs). We have used
      Unified Medical Language System (UMLS) semantic types (STs) to understand the
      percentage of GL text which belongs to a particular ST. We also use UMLS semantic
      network together with the CIGM-specific ontology to derive a semantic meaning
      behind the GL text. In order to achieve this objective, we took nine GL texts
      from the National Guideline Clearinghouse (NGC) and marked up the text dealing
      with a particular ST. The STs we took into consideration were restricted taking
      into account the requirements of a task-based CIGM. We used DARPA Agent Markup
      Language and Ontology Inference Layer (DAML + OIL) to create the UMLS and CIGM
      specific semantic network. For the latter, as a bench test, we used the 1999 WHO
      International Society of Hypertension Guidelines for the Management of
      Hypertension. We took into consideration the UMLS STs closest to the clinical
      tasks. The percentage of the GL text dealing with the ST "Health Care Activity"
      and subtypes "Laboratory Procedure", "Diagnostic Procedure" and "Therapeutic or
      Preventive Procedure" were measured. The parts of text belonging to other STs or
      comments were separated. A mapping of terms belonging to other STs was done to
      the STs under "HCA" for representation in DAML + OIL. As a result, we found that
      the three STs under "HCA" were the predominant STs present in the GL text. In
      cases where the terms of related STs existed, they were mapped into one of the
      three STs. The DAML + OIL representation was able to describe the hierarchy in
      task-based CIGMs. To conclude, we understood that the three STs could be used to
      represent the semantic network of the task-bases CIGMs. We identified some
      mapping operators which could be used for the mapping of other STs into these.

PMID- 14664032
TI  - Method for automatic management of the semantic network ambiguity in the UMLS:
      possible application for information retrieval on the Web.
AB  - The Unified Medical Language System (UMLS) is an extensive collection of terms
      and concepts. The UMLS includes biomedical terms from standard classifications.
      The semantic network (SN) links the concepts, sometimes ambiguously. In this
      paper we try, on one hand to describe the relationship between concepts more
      efficiently and on the other hand to find new relationships. Assuming that re
      usability and automatic extraction of knowledge from existing thesaurus enables
      an improvement of the metatheasaurus, we cross the SN with linked concepts from
      the ADM (Assisted Medical Diagnosis). Results are presented and our discussion
      concerns firstly the use of the SN only; secondly the improvement that allows pre
      selection of linked concepts, and thirdly the possibility to coincide with other
      developments that improve the metathesaurus.

PMID- 14664033
TI  - Integrating content-based visual access methods into a medical case database.
AB  - In the computer vision domain, content-based access methods to all forms of
      multimedia data are a hot research topic. A large number of tools have been
      developed to find documents in multimedia repositories and to manage the (visual)
      information that has been created, for example by the Internet. Although no
      general breakthrough has been achieved with respect to searching diverse
      databases with automatically extracted features, the techniques have gained
      acceptance in a few well-defined domains such as image agencies (Corbis) and
      trademark research. In the medical domain, the number of digital images produced
      and used for teaching, diagnostics and therapy is rising in a similar way as in
      other domains. Still, there are only a few image retrieval systems that use
      automatically extracted visual features for content-based access to medical image
      databases. This article describes the use of an open source image retrieval
      system (GIFT) that has been adapted for the use with medical images using the
      image case database CasImage that has been developed and maintained by the
      University Hospital of Geneva and that is in routine use. The first results show
      the potential of this technique to retrieve similar cases from a case database.
      This is an important task for teaching and might also become important for
      diagnostics using case-based reasoning, for example. For the use as a diagnostic
      tool, it is foreseen to specialize the visual features for the domain of lung
      image retrieval, using high resolution computed tomography (HRCT) images.

PMID- 14664034
TI  - Medical pedagogical resources management.
AB  - The main objective of this work is to help the management of training resources
      for students using a pedagogical network available at the Medical School of
      Rennes. With the increase of the number of connections and the number of medical
      documents available on this network, the management of new contents requires a
      lot of efforts for the webmaster. In order to improve the management of the
      resources, we implemented an automatic web engine for teachers, able to manage
      the links for the most interesting resources for their practice.

PMID- 14664035
TI  - Healthcare networks services for patients and large public: methodological and
      engineering issues.
AB  - In this paper, we analyse the services supplied by innovative and transversal
      healthcare organisations to satisfy patients and large public requirements and we
      illustrate them with the French healthcare networks. We classify these services
      in two groups, healthcare delivery services and health related information
      services, and we define three layers for their possible contexts. We will use an
      Information System perspective to investigate about various methodological
      approaches to realise each group of services and we compare their challenges and
      difficulties. Finally, we identify methodological and engineering issues common
      to both groups.

PMID- 14664036
TI  - Accurate searching using XML and topic maps.
AB  - Most clinical data is narrative text and often not accessible and searchable at
      the clinical workstation. We have therefore developed a search engine that allows
      indexing, searching and linking different kinds of data using web technologies.
      Text matching methods fail to represent implicit relationships between data, e.g.
      the relationship between HIV and AIDS. The ISO topic maps standard provides a
      data model that allows representing arbitrary relationships between resources.
      Such relationships form the basis for context sensitive searching and accurate
      search results. XML standards are used for the interchange of data relationships.
      Our approach has been applied to medical classification systems and clinical
      practice guidelines with promising results.

PMID- 14664037
TI  - The effect of sample size and MLP architecture on Bayesian learning for cancer
      prognosis--a case study.
AB  - In this paper we investigate the independent effects of training sample size and
      multilayer perceptron (MLP) architecture on Bayesian learning to build prognostic
      models for metastatic breast cancer. We trained two types of Bayesian neural
      networks on a data set of 1477 metastatic breast cancer patients followed at the
      Institut Curie using disjoint training sets of sizes k = 50, 100, 200, 300, and
      450. The learning performance as measured by an expected loss appeared
      independent of the two architectures modelling the log hazard function under
      either proportional or non proportional hazard assumptions, thus indicating that
      no other sources of nonlinearity besides interactions are present. We found a
      performance breakdown at k = 50, and no sample size effect for k > or = 100.

PMID- 14664038
TI  - On the use of vignettes for eliciting test-selection strategies.
AB  - Decision-support systems often include a strategy for selecting tests in their
      field of application. This strategy in essence captures procedural knowledge and
      serves to provide support for the reasoning processes involved. Generally, a test
      selection strategy is offered in which tests are selected sequentially. For our
      field of application, we noticed that such a strategy would be an
      oversimplification, and decided to acquire knowledge about the actual strategy
      used by the experts. To this end, we composed a method that comprised an
      unstructured interview to gain general insight in the test-selection strategy
      used, and a subsequent structured interview, simulating daily practice through
      vignettes, to acquire full details. We used the method with two experts in our
      field of application and found that it closely fitted in with their daily
      practice and resulted in a large amount of detailed knowledge.

PMID- 14664039
TI  - Clinical guidelines: a study of staff awareness of Internet resources.
AB  - Clinical guidelines (CGs) are widely used in community hospitals. The advantages
      and limitations of CGs are well understood by nurses and therapists. There are
      effective human dissemination routes using local training of link nurses and
      cascade learning. Practice development nurses are a useful resource for locating
      CGs. However there is a universal lack of awareness of Internet based national
      CGs in this sample of ward nurses and therapists. Access to these national CGs
      via the Internet would make local adaptation of CGs more effective and efficient.
      Access to Internet PCs on the wards backed up with staff training was
      recommended, and is ongoing.

PMID- 14664040
TI  - Combining risks estimations and clinical practice guidelines in a computer
      decision aid: a pilot study of the EsPeR system.
AB  - Many preventable diseases such as ischemic heart diseases or breast cancer are
      still not adequately managed in the population. Computerized decision support
      systems are one of the solutions for improving the quality of prevention
      strategies. We designed a system called EsPeR (Personalised Estimate of Risks)
      combining calculation of several risks and computerisation of guidelines (cardio
      vascular prevention, screening for breast cancer, colorectal cancer, uterine
      cervix cancer, and prostate cancer, diagnosis of depression and suicide risk). We
      present a qualitative evaluation of its ergonomics, its understanding and
      acceptance by a group of general practitioners. We organised 4 focus groups
      comprising 6-11 general practitioners. Physicians worked on several structured
      clinical scenario with help of EsPeR, and 3 senior investigators leaded
      structured discussion sessions. Initial sessions identified several ergonomics
      flaws that were easily corrected. Both clinical scenari and discussion sessions
      identified several problems of insufficient comprehension (expression of risks,
      definition of familial history of disease), lack of knowledge, and acceptance of
      recommendation by both the physician. Educational and organisational components
      (i.e. time constraints) as well as acceptance of evidence-based decision-making
      should be taken into account before launching computerised decision support
      system, or testing them in randomised trials.

PMID- 14664041
TI  - Interpretative framework of chronic disease management to guide textual guideline
      GEM-encoding.
AB  - The aim of this work is to develop an XML-based application for the automated
      generation of decision rules from a textual guideline encoded using the Guideline
      Elements Model (GEM). A formalization of guideline-based chronological steps of
      treatment has been proposed to resolve the semantic ambiguities of the original
      document. The GEM DTD has been extended in order to standardize both decision
      variable and action representations in recommendations. Under these assumptions,
      the 1999 Canadian Recommendations for the management of hypertension have been
      marked-up as a GEM-encoded instance of the extended DTD. An XML parser has been
      used to extract the relevant elements as IF and THEN clauses of decision rules.
      This GEM application generated 104 rules to be compared to the 98 rules manually
      developed from the same guideline during the ASTI project.

PMID- 14664042
TI  - Modeling patient-specific therapeutic strategy in the guideline-based management
      of a chronic disease.
AB  - Like any chronic disease, hypertension is complex to manage. Despite the
      availability of evidence-based clinical practice guidelines in most countries, a
      lot of hypertensive patients remain inadequately managed. One difficulty lies in
      the synchronization of a patient's own therapeutic history with the guideline
      strategy. We propose a formal model to represent guideline-based therapeutic
      strategies as bi-dimensional matrices. We built the knowledge base as a two-level
      decision tree to be read during an hypertextual navigation. The first level is
      used to identify a patient-specific clinical situation on the basis of key
      elements of clinical examination (complication of hypertension, associated
      diseases). The second level aims at dynamically refining the theoretical
      strategy, a priori established in the guideline for the corresponding clinical
      situation, by the specific therapeutic history of the patient. Finally, depending
      on the patient's response to the ongoing treatment, the system provides a
      recommendation consistent with the guideline strategy, whatever the patient's
      past treatments. A first evaluation of the system on simulated cases has been
      well accepted by general practitioners.

PMID- 14664043
TI  - An ontological approach to evidence-based medicine and meta-analysis.
AB  - The "evidence-based medicine" (EBM) paradigm is centered on the concept of "best
      evidence" and clinical studies based on this approach are more likely to be
      considered by physicians in their practice. In this paper we describe an ontology
      representing the concepts involved in evidence-based medicine and meta-analysis
      and show how an ontological approach can be applied both for revisiting EBM
      conceptual foundations and for allowing a more effective knowledge-based
      information retrieval in literature.

PMID- 14664044
TI  - How many neurologists/epileptologists are needed to provide reliable descriptions
      of seizure types?
AB  - We are developing seizure descriptions as a basis for decision support. Based on
      an existing dataset we used the Spearman-Brown prophecy formula to estimate how
      many neurologist/epileptologists are needed to obtain reliable seizure
      descriptions (rho = 0.9). By extending the number of participants to the required
      level we found that the number of participants needed to obtain a reliability
      coefficient of 0.9 were in accordance with the number of participants determined
      from the Spearman-Brown prophecy formula. Systematic differences between the
      participants were minor and not statistically significant.

PMID- 14664045
TI  - Getting evidence to prescribers and patients or how to make EBM a reality.
AB  - Bringing all available evidence on therapy efficacy to users is a necessary step
      in the evidence-based medicine paradigm. Today, the needs of physicians in
      medical information, including therapeutic information, are not met. Further, the
      information reaching the doctors is rarely consistent with the available
      evidence. The growth rate of emerging evidence and its increasing complexity make
      the doctors unable to cope with it within the current medical information system.
      So, there is a real need to sort out a new way for transferring therapeutic
      information to doctors and patients. We conceived a new paradigm and designed an
      Internet process based on it by which unbiased evidence is brought to doctors in
      such a format that it can be accessed and used during the visit.

PMID- 14664046
TI  - Fusing a systematic and a case-based repository for medical decision support.
AB  - In order to take full advantage of computer-based decision support in clinical
      practice, it makes sense to combine systems which support the same subject, but
      contribute to this task in different ways. At the Technical University of Munich,
      a Combined Clinical Decision Support System (C-CDSS) of this kind has been
      designed for gastroenterologists. The main goal of the system is to help the
      physicians in finding information which is relevant for making the right
      diagnoses or applying the proper therapy to his patients. To achieve this goal,
      not only systematic knowledge of the medical domain, but also case-based data is
      useful for a comparison of the actual case with well-documented similar cases of
      colleagues. The systematic knowledge comprises state-of-the-art textual
      information and selected multimedia contents in the sense of a standard textbook.
      The case-based information includes practice-related information on a pool of
      anonymized cases from clinical routine and also demonstrations of new techniques.
      By integrating these information resources into one service via a rule-based
      retrieval system, a powerful decision support system can be generated.

PMID- 14664047
TI  - Modelling of a case-based retrieval system for oncology.
AB  - When a new patient does not comply with the guidelines, experts base their
      therapeutic decisions on similar patients' cases they have treated in the past.
      The case-based reasoning decision-support system we propose will automatically
      compare the patient's case to the structured guideline, then to other cases, and
      retrieve similar cases. The general structure of the system is presented here,
      the domain of application being oncology. As the patients' records are not stored
      in the current database in a format directly exploitable, an object-oriented
      model is proposed, that includes prognosis factors currently tested in clinical
      trials, well-established ones, and a description of the illness' episodes. Such
      system does not exist in the literature. It can be viewed as a data warehouse.
      Future work consists in defining the similarity measures, and connecting the
      system to the current database.

PMID- 14664048
TI  - A prognostic model for temporal courses that combines temporal abstraction and
      case-based reasoning.
AB  - Since clinical management of patients and clinical research are essentially time
      oriented endeavours, reasoning about time has recently become a hot topic in
      medical informatics. Here we present a method for prognosis of temporal courses,
      which combines temporal abstractions with Case-based Reasoning. We have applied
      our method in two programs. The first one deals with multiparametric time course
      prognosis of the kidney function. The intention of the second program is to
      compute early warnings against approaching infectious diseases like influenza.

PMID- 14664049
TI  - Software support for organ transplant management.
AB  - This paper focuses on the Organ Transplant Management (OTM) process defined as
      the set of activities that need to be coordinated before the surgery operation
      itself can take place. The main goal is to understand how the different OTM tasks
      are interrelated, in order to build an innovative software system that aims to
      support medical practitioners involved in the various decision-making steps. The
      current work and the extensive discussions with experts in this area provided
      ground for the definition of the OTM system. We argue that this tool, when
      integrated in real hospitals and transplant centres, will facilitate many of the
      tasks currently performed by humans, and will allow optimisation of precious
      resources such as time and personnel.

PMID- 14664050
TI  - Teaching Arden Syntax using a simulated environment.
AB  - The Arden Syntax is a simple syntax that allows physicians to encode medical
      knowledge in small modules, called medical logic modules (MLM). These MLM are
      well suited to data-driven alerts and reminders. While the Arden syntax is simple
      to teach, the students are most of the time limited to the writing of modules and
      the verification of the module's syntax. Our work proposes an environment that
      simulates various elements required by MLMs, allowing the students to execute the
      MLMs they have written immediately. This provides the necessary feedback to
      understand in depth the inner workings of MLMs.

PMID- 14664051
TI  - Automatic detection of microcalcifications in mammography using a neuromimetic
      system based on retina.
AB  - The incidence of breast cancer in France is roughly 26,000 and the annual number
      of deaths is 11,000. The mammography is the choice examination for the early
      identification of the tumours in an asymptomatic population. This is a simple,
      reliable, inexpensive examination, allowing to identify a grave and frequent
      pathology, but that can be the object of an effective treatment if early
      detected. The recognition of the microcalcifications in the mammographies is the
      key for early detection of cancers. Automatic detection methods were already
      proposed, but they have a very weak specificity and a relatively low sensibility.
      Currently, the eye of the expert still remains the better judge. We propose a
      neuromimetic method to localize automatically the microcalcifications. In this
      method, we devise a network of formal neurones inspired from the mammal retina
      architecture. This model mimics one characteristic of the retina which is is a
      sensor that automatically adapts to the image characteristics to analyse and
      realize the outlines extraction and adaptative filtering of the pictures, based
      on its network properties. The results were tested using a public standardized
      data set (DDSM), which was designed to test the automatic detection methods. We
      show that our "retina" can extracts most of the microcalcifications that can be
      grouped together in clusters. While we achieve a 95% sensitivity, we must
      acknowledge a low specificity (22%). Current efforts will focus to enhance this
      latter parameter.

PMID- 14664052
TI  - Watching symptoms and illnesses through the eyes of Multiple Correspondence
      Analysis: a case study in toxicology.
AB  - The goal of the reported research was the design of a computerized tool aimed at
      aiding an emergency specialist, in a toxicological emergency unit, to quickly
      identify, at the admission time, the various poisons ingested by a comatose
      patient. This medical decision making problem has been proved to be
      computationally intractable since a lot of patient cases sharing the same
      clinical table have different diagnoses in terms of psychotropes combinations.
      The paper explores the idea that the outcome of Multiple Correspondence Analysis
      (MCA), a mathematical data analysis method, can be thought of as visual and
      analytical aids for the physician facing this decision problem. We argue that the
      expert's clinical reasoning can be enhanced by the factorial maps and some
      computerized results provided by MCA. Using a learning database of 505 diagnosed
      cases, we realized a whole decision aiding system called TOXSYMEDIA. A test-base
      of 97 patients was used to partially assess the system. The method and resulting
      tool revealed to be appreciable to early inform the physician about the possible
      combination of ingested psychotropes.

PMID- 14664053
TI  - Quality assurance and certification of health IT-systems communicating data in
      primary and secondary health sector.
AB  - Each year more than 70% (25 mill) of all electronic health documents between
      secondary and primary health sector in Denmark are exchanged electronically using
      European EDI standards. Despite this widely use there have been several problems
      in showing the transferred data in correct and full context. These problems are
      solved in the 3 years MedCom certification and consolidation project. The project
      financed by Ministry of Health, Danish County Association and others through
      MedCom, involved all relevant health professional groups, organisations, all SW
      suppliers and all local governments. A new detailed and exact documentation with
      recommendations and obligatory needs published in "The Good EDI letters" was
      made, followed by training courses for programmers, test and certification of IT
      systems by MedCom and finally implementation of certified systems by all users in
      the country. The certification and implementation process are followed on
      www.medcom.dk The results are now a high quality of information and the state of
      art: One and only way of exchanging documents which are accepted by health
      professionals and implemented by all SW companies at all users. To day only
      MedCom certified IT systems are used[2] and the certification is a must for SW
      companies to be in the market.

PMID- 14664054
TI  - Tracing computerized incidents to manage and improve quality health care in
      hospitals.
AB  - The promotion of quality and safety care in public and private Hospitals has
      become a crucial stake. To succeed in this, a quality process is necessary for
      quality management. To set it up, it is necessary to have different piloting
      tools. Data collection of effective information is one of these tools. It is
      necessary to be able to process the data quickly in order to answer the various
      demands rapidly. This project consists in proposing the possibility of declaring
      different dysfunctions and incidents by a simple formula integrated into the
      intranet services of the hospital for the medical, nursing and administrative
      staff. This should lead to quality management of the medical units.

PMID- 14664055
TI  - A framework for evaluation of medical information systems.
AB  - The evaluation of information systems, especially in the health care field, is a
      complex task. While in the general information system science field there have
      been several attempts to build frameworks and models to understand better the
      evaluation of information systems, in health care such models have been non
      existent. Unfortunately general frameworks cannot be exactly applied for the
      evaluation of medical information systems, because they do not recognise the
      specific nature of the medicine. This article represents an attempt at
      formulating conceptual models to understand the evaluation of the different
      impacts of medical information systems.

PMID- 14664056
TI  - Cardiovascular risk calculators: understanding differences and realising economic
      implications.
AB  - In recent years, the concept of "global cardiovascular risk assessment" has grown
      in interest for its role in primary prevention of cerebro-cardiovascular
      diseases. Interventions for reducing the risk of relapse for persons with past
      history of these diseases are well agreed-on. On the contrary, the risk status of
      persons without such a history varies greatly, and this variability implies a
      range in the intensity of interventions. In several countries, guidelines for
      general practitioners have been diffused about pharmaceutical prescriptions in
      presence of various risk degrees. In particular, in Italy, a governmental drug
      management commission has established that statins, the most used cholesterol
      lowering medicines, can be refunded by the National Healthcare System only if
      prescribed to hyper-cholesterol patients with a global risk greater than 20%. The
      question is: how to calculate the risk? We performed a review of both the web and
      the literature and we found a lot of different "risk calculators". By means of a
      simulation study, we showed that these tools, when applied to the same person,
      may lead to very different results. We estimated the economic impact of using one
      or another calculator.

PMID- 14664057
TI  - ADEMA: a decision support system for asthma health care.
AB  - Asthma is a distressing disease, affecting up to 7% of the French population and
      causing considerable morbidity and mortality. A medical decision support system
      such can help physicians to control this chronic disease. Thanks to the health
      care network (RESALIS) of Fedialis Medica (disease management branch from
      GlaxoSmithKline), asthma consultation data were collected to exploit them. We
      chose Case-Based Reasoning paradigm to develop our medical decision support
      system. Intelligent data analysis methods have been used to determine the case
      model for our system. Our similarity metric is based on the MVDM method. We
      developed two methods to reuse retrieved cases. We present our data analysis
      results and similarity metric from which we designed our Case Based System for
      asthmatic patients health care: ADEMA. To conclude, an evaluation of ADEMA is
      presented.

PMID- 14664058
TI  - Using mobile information technology to build a database for anesthesia quality
      control and to provide clinical guidelines.
AB  - The paper describes a mobile information system to collect patient information
      for anaesthesia quality control. In this system we use handheld computers, to
      collect patient data at the bedside with a daily synchronization of the data of
      the anaesthesiologist's handheld with the anaesthesia database center, later used
      for quality control analysis. Further, we design mobile clinical guidelines to be
      used on the same handhelds.

PMID- 14664059
TI  - A UML approach to process modelling of clinical practice guidelines for
      enactment.
AB  - Although clinical practice guidelines (CPGs) have been suggested as a means of
      encapsulating best practice in evidence-based medical treatment, their usage in
      clinical environments has been disappointing. Criticisms of guideline
      representations have been that they are predominantly narrative and are difficult
      to incorporate into clinical information systems. This paper analyses the use of
      UML process modelling techniques for guideline representation and proposes the
      automated generation of executable guidelines using XMI. This hybrid UML-XMI
      approach provides flexible authoring of guideline decision and control structures
      whilst integrating appropriate data flow. It also uses an open XMI standard
      interface to allow the use of authoring tools and process control systems from
      multiple vendors. The paper first surveys CPG modelling formalisms followed by a
      brief introduction to process modelling in UMI. Furthermore, the modelling of
      CPGs in UML is presented leading to a case study of encoding a diabetes mellitus
      CPG using UML.

PMID- 14664060
TI  - Evaluation of user acceptance of information systems in health care--the value of
      questionnaires.
AB  - The use of modern information technology (IT) offers tremendous opportunities
      such as reducing clinical errors and supporting health care professionals in
      providing care. Evaluation of user satisfaction is often seen as a surrogate for
      the success of an information systems. We will present the evaluation of a report
      writing system at the Innsbruck University Medical Center based on a
      standardized, validated psychometric questionnaire. The results show high
      reliability and validity of the questionnaire. They also show some interesting
      differences in user satisfaction between departments, due to differences in
      working processes and preconditions. Psychometric questionnaires can be seen as a
      reliable and valid method to measure certain psychological constructs. Their
      development requires, however, methodological rigour and sufficient time.
      Psychometric questionnaires allow only a limited interaction between researcher
      and user, their results may be very dependant on the time of measurement, and
      their interpretation often needs external knowledge. Those limitations have to be
      taken into account when preparing evaluation studies.

PMID- 14664061
TI  - Multidimensional evaluation of a Clinical Information System for anaesthesiology:
      quality management, usability, and performances.
AB  - This paper describes a multi-dimensional assessment methodology to support the
      choice and selection process of Clinical Information Systems. The methodology
      includes 4 evaluation components: Fulfilment of Users Requirements, Usability
      Inspection, Usability Testing and Performance Evaluation. The methodology is
      illustrated with the case study of a selection of a CIS for anaesthesiology. It
      proved to be very efficient and powerful to support the selection process, to
      enhance users' involvement in the project, and to initiate the necessary re
      engineering of the HCI.

PMID- 14664062
TI  - Diabetes websites accredited by the Health On the Net Foundation Code of Conduct:
      readable or not?
AB  - Health information posted on the Internet has become a popular mode of
      communication with the population at large because millions of people now use the
      Internet to gather health information. Many studies on readability have shown
      that patient education information is frequently written at the reading level too
      high for the average population to understand, and the same holds true for health
      information on the Internet. The aim of this study was to determine the
      readability levels of health information found on diabetes-related websites
      displaying HONcode logo, which indicates to high quality of the information
      provided. The 99 websites tested for readability using the Flesch Reading Ease
      formula and Flesch-Kincaid level showed FRE score 2.1 to 79.6, with the mean 41.7
      (10th grade, 8th month Flesch-Kincaid level), which indicates that 86.9% of these
      materials would be too difficult to read for the average adult population. It is
      suggested that the readability level, and the name of the formula used, be used
      on the websites themselves to help the Internet users decide which sites could be
      of the greatest benefit to them.

PMID- 14664063
TI  - Societal dimensions of third-party evaluation of Internet health content.
AB  - Rating and certification of Internet health content have been suggested as
      strategies to guide citizens to high quality information. Attempts to rate
      Internet content, however, have been criticised for being unfeasible or
      undesirable. We created and tested a novel concept and technology to evaluate
      online health resources. In this paper, we view various societal issues and
      suggest solutions whenever possible. Rating and certification of Internet content
      should be preceded by a consideration and discussion that has many societal
      dimensions.

PMID- 14664064
TI  - MedCIRCLE: collaboration for Internet rating, certification, labelling and
      evaluation of health information on the World-Wide-Web.
AB  - We describe MedCIRCLE, an EU-funded semantic web project to implement the first
      steps towards a global, collaborative rating and guidance system for health
      information proposed in the MedCERTAIN project. In MedCIRCLE, three European
      gateway sites for consumer health information will implement the metadata
      vocabulary HIDDEL (Health Information Disclosure, Description and Evaluation
      Language). HIDDEL allows portals and gateways to make the results of their
      evaluations accessible as XML/RDF. The three participating national portals are:
      AQUMED (Agency for Quality in Medicine) patienten-information, de, COMB (Official
      Medical College of Barcelona) and CISMeF, a quality-controlled health gateway
      developed at Rouen University Hospital. Other health subject gateways,
      accreditation, or rating services are invited to join the collaboration simply by
      implementing HIDDEL on their gateways. Widespread implementation HIDDEL will
      allow intelligent agents or client-side software to harvest statements and
      opinions about the trustworthiness of other websites, assisting users in
      selecting trustworthy websites. The MedCIRCLE project builds on, expands and
      continues work on rating health information on the Internet piloted within the
      MedCERTAIN project. While MedCERTAIN provided the core technologies and software
      for rating and "trustmarking" health information, MedCIRCLE is built around these
      technologies and involves a wider medical community to assess health information,
      demonstrating the power of collaborative and interoperable evaluations in a
      semantic web environment. MedCIRCLE is a project with the overall objective to
      develop and promote technologies able to guide consumers to trustworthy health
      information on the Internet, to establish a global web of trust for networked
      health information, and to empower consumers to positively select high quality
      health information on the web. Other aims include refinement and expansion of
      HIDDEL, to become a standard vocabulary and interchange format for self- and
      third-party ratings of health information.

PMID- 14664065
TI  - Structure data entry using graphical input: recording symptoms for multiple
      sclerosis.
AB  - Structured Data Entry provides flexible and efficient input to the computer-based
      patient record. We have utilized the SDE approach to build a prototype interface
      for recording common symptoms associated with Multiple Sclerosis (MS). The
      software provides both graphical input and output, to facilitate efficient data
      entry and monitoring of data. Graphical input is transformed to textual
      information, which is stored in a database in a hierarchical tree structure. Pain
      management in MS may be achieved by careful monitoring of the symptom in response
      to treatment. Pain location is selected on a body image and severity and other
      attributes represented using a graphical visual analog scale, leading to more
      convenient input and a less ambiguous coding than is achievable with narrative
      text alone. This approach could provide an objective means of monitoring the
      progress of the disease and management of the symptoms. The intuitive interface
      may also facilitate self-monitoring.

PMID- 14664066
TI  - Making messaging standards work: from definition to interoperability at runtime.
AB  - The synchronisation of data between healthcare IT applications is done by
      exchanging (in the broader sense) messages which are formatted according to one
      of many standards that are used in healthcare. The most successful standard
      enabling such communication and co-operation for health is HL7 established in the
      mid-eighties starting as a communication standard within hospitals. HL7 included
      soon other domains such as home care, clinical studies, and prescription
      communication. So, HL7 supports shared care between primary, secondary and
      territory healthcare establishments. Another very successful standard is DICOM
      for communicating image information among modalities and (radiology) information
      systems. This review paper discusses integration issues for specification and
      development of messaging standards and their impact on applications.

PMID- 14664067
TI  - Web versus press with a high circulation: an Italian case study.
AB  - THE PROBLEM: the quality of health-related information available for general
      public on the web has been widely debated, often expressing concern, in the last
      few years, but also other mass media supply medical contents for health consumer.
      THE OBJECTIVE: To evaluate the quality of information available by the Italian
      people through Internet in comparison with the one published on the press with a
      high circulation. A general interest topic such as over-weight and obesity has
      been identified as a convenient field for the comparison. METHODS: A sample of
      web sites and articles have been collected--excluding the promotional ones- in
      order to compare their completeness and correctness. National guidelines were the
      golden standard. For the web sites, the availability of indications to let the
      user know the reliability of the site--we will refer to these as "transparency"-
      has been evaluated through 9 parameters. RESULTS: 45 informative sites and 35
      articles have been found: the Italian population has a good chance of getting
      information. Web sites are much more complete than articles. Correctness of both
      is quite good. Transparency of web sites leaves much to desire, independently
      from the quality of the content. LESSON LEARNT: There is probably an excessive
      confidence about the transparency and caution of articles in dealing with health
      related topics. CONCLUSION: The web publishers must necessarily be educated to
      apply the existing good practice rules, but in the meantime also the press with a
      high circulation, that is read by a high percentage of people, has to improve its
      quality in order to co-operate in supplying adequate information. In general,
      from the traditional exceptionalist approach for medical information on the
      internet, a definition of media quality standard could be derived.

PMID- 14664068
TI  - Patient relation management: a relevant solution to connect the links of a
      healthcare chain.
AB  - The USIT-tool is used to investigate the health care chain of Multiple Sclerosis
      (MS) in a Dutch region. The advantage of the USIT-tool is that is results in
      insight in the relevant problems, solutions and constraints of the caregivers
      both in the organisational and the information technological area. The main
      problem in the MS-health care chain proved to be the lack of co-ordination and
      the inefficient communication between caregivers. Although most caregivers were
      convinced of the need to improve delivered care for MS-patient, most of them also
      expressed that they would spend little time and energy on improving MS-care,
      because of the low relevance of MS-care compared to other kinds of care. To
      improve care, taking in account this constraint we propose to build a Patient
      Relation Management (PRM) System. A PRM is a simple web-based application that is
      based on agreement by the caregivers about the route an MS-patient should follow
      through health care. PRM supports routing, tracking and tracing of a patient and
      supplies the caregivers with professional guidelines. The PRM-concept can easily
      be expanded to other patient groups or diseases and can serve as a first step to
      a regional Electronic Patient Record. It is likely that we would have suggested a
      far more complicated ICT solution if we had only analysed the MS-care process as
      such, without specific consideration of the USIT dimensions. The USIT analysis
      helped us to balance the breadth of the proposed solution with the nature of the
      situation the future users of the system are in.

PMID- 14664069
TI  - Opinions and e-health behaviours of patients and health professionals in the
      U.S.A. and Europe.
AB  - BACKGROUND: There exists a gap in the use of Internet for health purposes between
      patients and health professionals and between various countries. The Internet has
      the potential to be a global tool for health professionals and their patients
      but, as seen in other fields, cultural differences may lead to divergent opinions
      and preferences. OBJECTIVE: To identify the opinions, preferences and types of
      behaviours regarding the use of Internet for health purposes, for health
      professionals and patients in selected regions of the United States and Europe.
      METHODS: An announcement of an online survey was posted on more than 100 web
      sites during May and June of 2002. Members of HONnewsletter were also invited via
      email. The online questionnaire consisted of 28 questions with sections designed
      specifically for patients or health professionals. Sub-samples of respondents
      were created based on their geographic location. RESULTS: 2621 respondents mainly
      from the United States (38%, n = 984) and Europe (29%, n = 739) completed the
      survey. For the USA, the majority of respondents were patients (68.7%), while in
      Europe, the majority were health care professionals (63.6%). In both regions,
      health professionals preferred using medical search tools but patients preferred
      general search tools. Concerns about the accuracy of information and
      trustworthiness were shared by all groups. The majority of respondents reported
      that they preferred certified web sites. The patients from USA (69%) and Europe
      (47%) have discussed the results of their Internet searches with their doctors,
      while health professionals are receptive to the discussion and find it helpful.
      Other e-health behaviours are also reported by both parties. CONCLUSION: Based on
      the self- reported e-health behaviours noted in this study it appears that the
      use of the Internet for health purposes is growing in importance to the patient
      physician relationship in Europe and the USA.

PMID- 14664070
TI  - Modelisation of consumer health information in a quality-controlled gateway.
AB  - The amount of health data accessible on the Web is increasing and Internet has
      become a major source of health information. Many tools and search engines are
      available but medical information retrieval remains difficult for both the health
      professional and the patients. In this paper we describe CISMeF-patients. It is a
      sub-part of CISMeF, a structured quality-controlled subject gateway. CISMeF
      patients has been designed for the patients, their families and the general
      public who are often unfamiliar with the medical domain and the medical
      vocabulary. The resources included in CISMeF-patients are described using the
      Dublin Core metadata format. To index them, CISMeF-patients and CISMeF share the
      same terminology, which 'encapsulates' the MeSH thesaurus with a layer of
      synonyms. Unlike Medline-plus and Medline, sharing the same terminology allows to
      a CISMeF-patients end-user the possibility to extend his query to the CISMeF
      catalogue (e.g. for searching teaching resources or clinical guidelines).

PMID- 14664071
TI  - Metadata element set in a quality-controlled subject gateway: a step to a health
      semantic Web.
AB  - BACKGROUND: Quality-controlled subject gateways are Internet services which apply
      a selected set of targeted measures to support systematic resource discovery.
      Considerable manual effort is used to process a selection of resources which meet
      quality criteria and to display a extensive description and indexing of these
      resources with standards-based metadata. OBJECTIVE: Several metadata element sets
      are proposed to describe, index and quality health resources to be included in a
      French quality-controlled health gateway called CISMeF. The main objectives were
      to enhance Internet health document retrieval and navigation, and to allow
      interoperability with other Internet services. RESULTS: The Dublin Core metadata
      element set is used to describe and index all Internet health resources included
      in CISMeF. For teaching resources, some elements from IEEE1484 Learning Object
      Metadata are also used. For evidenced-base medicine resources, specific metadata
      are employed which assess the health content quality. The HIDDEL metadata set is
      used to enhance transparency, trust and quality of health information on the
      Internet. CONCLUSION: Comprehensive metadata element sets can be extremely useful
      to describe, index and assess health resources on the Internet in a quality
      controlled subject gateway. Machine-readable metadata creates an Semantic Web
      which is more efficient for end-users as compared to the current Web.

PMID- 14664072
TI  - Indexing method of digital audiovisual medical resources with semantic Web
      integration.
AB  - Digitalization of audio-visual resources combined with the performances of the
      networks offer many possibilities which are the subject of intensive work in the
      scientific and industrial sectors. Indexing such resources is a major challenge.
      Recently, the Motion Pictures Expert Group (MPEG) has been developing MPEG-7, a
      standard for describing multimedia content. The good of this standard is to
      develop a rich set of standardized tools to enable fast efficient retrieval from
      digital archives or filtering audiovisual broadcasts on the internet. How this
      kind of technologies could be used in the medical context? In this paper, we
      propose a simpler indexing system, based on Dublin Core standard and complaint to
      MPEG-7. We use MeSH and UMLS to introduce conceptual navigation. We also present
      a video-platform with enables to encode and give access to audio-visual resources
      in streaming mode.

PMID- 14664073
TI  - SIGAPS: a prototype of bibliographic tool for medical research evaluation.
AB  - Evaluation of research activity is extremely important but remains a complex
      domain. There's no standardized methods and evaluation is often based on the
      scientific publications. It is easy to identify, for a researcher, all the
      publications realized over a given period of time. At the level of an important
      establishment like an University Hospital, with about 500 researchers, this sort
      of inventory is very difficult to realize: we have to list the researchers, to
      list their publications, to determine the quality of articles produced, to store
      retrieved data and to calculate summary statistics. We have developed a full-Web
      prototype, using free software which, for a given researchers' list, interrogates
      the Pubmed server, downloads the found references and stores them in a local
      database. They are then enriched with local data which allow the realization of
      more or less complex analyses, the automatic production of reports, or keyword
      search. This tool is very easy to use, allowing for immediate analysis of
      publications of a researcher or a research team. This tool will allow to identify
      those active teams to be maintained or emergent teams to be supported. It will
      also allow to compare candidate profiles for appointments to research posts.

PMID- 14664074
TI  - Development of an indexing search engine for the UMVF: proposal for an indexing
      method based on Dublin Core and XML.
AB  - The UMVF (French Virtual Medical University) has many heterogeneous resources
      hosted by the servers of university partners of the project. One of its
      objectives is to develop an efficient tool to perform a single search on these
      resources. We first defined a standardized and interoperable indexing method. For
      each document, an XML file containing information on the fifteen elements of
      Dublin Core was created. We checked its structure and content with a DTD. If the
      XML file was valid, its data were then integrated into a central database from
      which the engine carried out a search. We tested our tool successfully with the
      resources hosted by the Rennes Laboratory of Medical Informatics in cooperation
      with the Radiology Medical Campus [1]. Our method allows the standardization of
      the production of information by the various servers and it conforms to the
      constraints of the semantic Web owing to the technologies chosen.

PMID- 14664075
TI  - Personalising e-learning modules: targeting Rasmussen levels using XML.
AB  - The development of Internet technologies has made it possible to increase the
      number and the diversity of on-line resources for teachers and students.
      Initiatives like the French-speaking Virtual Medical University Project (UMVF)
      try to organise the access to these resources. But both teachers and students are
      working on a partly redundant subset of knowledge. From the analysis of some
      French courses we propose a model for knowledge organisation derived from
      Rasmussen's stepladder. In the context of decision-making Rasmussen has
      identified skill-based, rule-based and knowledge-based levels for the mental
      process. In the medical context of problem-solving, we apply these three levels
      to the definition of three students levels: beginners, intermediate-level
      learners, experts. Based on our model, we build a representation of the
      hierarchical structure of data using XML language. We use XSLT Transformation
      Language in order to filter relevant data according to student level and to
      propose an appropriate display on students' terminal. The model and the XML
      implementation we define help to design tools for building personalised e
      learning modules.

PMID- 14664076
TI  - Comparative assessment of two interfaces for delivering a multimedia medical
      course in the French-speaking Virtual Medical University (UMVF).
AB  - The UMVF aims at helping medical students during their normal curriculum via the
      facilities provided by Internet based techniques. This paper describes a
      comparative assessment of two interfaces delivering a multimedia course: a
      conventional web server (WS) and an integrated e-learning platform in the form of
      a Virtual Campus (VC). Eleven students were arbitrarily divided into two groups.
      We used a qualitative method for comparing their acceptance of the on line course
      provided by the two different interfaces. The two groups were globally satisfied.
      However, a decrease in satisfaction was noted at the end of the experimentation
      in the VC group. This may be explained by a more complex Graphical User Interface
      (GUI) of the VC and some constraints which do not exist with the WS. The current
      e-learning platforms are probably not optimised for working conditions where
      presential and virtual activities are mixed. We think that a new type of "light"
      platforms should be developed for these specific working conditions. Students of
      the two groups also had limitations about the multimedia environment. They may
      change their opinion if they get more accustomed with the multimedia environment
      and if their teachers make a more adequate use of the multimedia techniques.

PMID- 14664077
TI  - An approach to enrich online medical Problem-Based Learning with tacit healthcare
      knowledge.
AB  - Existing Problem-Based Learning (PBL) problems, though suitable in their own
      right for teaching purposes, are limited in their potential to evolve by
      themselves and to create new knowledge. Presently, they are based on textbook
      examples of past cases and/or cases that have been transcribed by a clinician. In
      this paper, we present (a) a tacit healthcare knowledge representation formalism
      called Healthcare Scenarios, (b) the relevance of healthcare scenarios in PBL in
      healthcare and medicine, (c) a novel PBL-Scenario-based tacit knowledge
      explication strategy and (d) an online PBL Problem Composer and Presenter (PBL
      Online) to facilitate the acquisition and utilisation of expert-quality tacit
      healthcare knowledge to enrich online PBL. We employ a confluence of healthcare
      knowledge management tools and Internet technologies to bring tacit healthcare
      knowledge-enriched PBL to a global and yet more accessible level.

PMID- 14664078
TI  - Ten years of medical informatics education experience at the Faculty of Medicine
      in Sarajevo.
AB  - INTRODUCTION: The medical informatics as the separate medical discipline very
      quickly gets developed, both in Bosnia and Herzegovina. In our country, the
      medical informatics is a separate subject for the last ten years, regarding to
      the Medical curriculum at the biomedical faculties in Bosnia and Herzegovina is
      in accordance with the project of the education related to Bologna declaration
      and the project EURO MEDICINA. This year the Chair of the Medical Informatics of
      the Medical Faculty in Sarajevo celebrates ten years of its existence. WORK
      METHOD: By the descriptive method of the research which included the
      questionnaire of about 400 students of the biomedical faculties, we established
      the attitudes and we took into consideration opinions of the students of these
      faculties about the validity of the contents of the subject of the medical
      informatics, the availability of the adoption of the material by the theoretical
      and practical performance of the teaching process and the suggestions and
      recommendations of the students about the contents that have to be throwned out
      from the curriculum and the teaching material that needs to be included. WORK
      RESULTS: The research was performed using the separate questionnaire pattern data
      carriers with the defined characteristics for the quality assessment of the
      performed course. The total attitude of the assessed students speaks about
      dominantly expressed satisfaction with the majority of the parameters that are
      important for assessment of the quality and the tuition contents that was
      evaluated during the questionnaire. The results are shown in the tables and
      graphs, and they are describing the program of the tuition and the contents of
      the methodical units, and the system of the examination for the students using
      the method of "multiple choice". CONCLUSION: The education in the field of the
      medical informatics is based at the concept which is used in the developed
      countries of the world, and according the recommendations of the working groups
      of the European and world association of the medical informatics. The theoretical
      and practical teaching and training performance in the wholeness is performed by
      use of the computer equipment, and the final knowledge check of the students also
      is performed using the Data Base Management System MSAccess specifically designed
      to cover full teaching and training material by using questions set in the data
      base which encircled nearly 1500 questions combinations.

PMID- 14664079
TI  - WASP--a generic web-based, interactive, patient simulation system.
AB  - Computer based patient case simulation systems have during the recent years been
      introduced in medical education to allow students to "meet" more cases that are
      educationally optimized and adapted to the actual learning situation. However,
      three major problems exist with most computer based case simulation systems
      today: They are expensive to develop, experienced multimedia developers are
      needed for the development and teachers/clinicians can not develop and adjust
      cases to fit their own specific educational needs. The WASP project (Web
      Activated Simulation of Patients) tries to solve these three problems, and still
      allow very realistic and highly-interactive simulations of clinical cases,
      delivered and edited via the Web. WASP is based on experience from a number of
      national and international visualization and simulation projects. Most important
      case simulation features are available, including: interactive history taking,
      complete physical examination (inspection, auscultation, palpation, percussion,
      vitals, neurological exams etc.), complete lab section including chemical labs, X
      ray, MRI, ultrasound, CT, phys lab, pharmacology lab, pathology lab etc.),
      diagnosis and differentials, therapy, interactive session feedback and integrated
      references and online database sources.

PMID- 14664080
TI  - Design considerations for a personalised patient education system.
AB  - Patient education is a significant factor in the provision of health care
      services, contributing to improved disease management and health care outcomes.
      In order to be most effective, patient education should be adapted to the
      characteristics of the individual recipient. Computer-based approaches have been
      explored as a possible means of achieving this goal. The success and capabilities
      of the resulting applications have been restricted by the absence of a direct
      link to patient data and the reliance on locally produced written material, which
      is expensive to produce, update and tailor. In our research project STructured
      Evaluated Personalized Patient Support (STEPPS), we are investigating the
      potential of a novel strategy for personalized or tailored patient education,
      based on the integration of electronic patient record data and material derived
      from online health information and knowledge resources. In this paper we present
      an overview of the pertinent technical issues and the way we have addressed them
      in the context of our development work in the domain of burn care. Further, we
      discuss how the choices made in the design of the system interrelate with the
      considerations for its implementation in health care practice settings.

PMID- 14664081
TI  - Similarity study on university teaching hospitals in France.
AB  - The recent development of hospital information systems in France presently makes
      it possible to study similarity between establishments based on an official data
      source, the AGHN. The AGHN is based on three types of information: medical,
      structural (personnel and material) and economic. Using the PCA (principal
      component analysis) tool, we can examine the situation of one regional and?or
      university hospital with regards to others of the same kind.

PMID- 14664082
TI  - A framework for benchmarking hospital performance: application to surgical site
      infection.
AB  - Benchmarking is an approach to quality improvement where practice of leaders are
      studied to help improve one's own practice. Here, a framework for designing and
      implementing an information system for benchmarking is proposed. Participating
      actors are described by Structure, Process, Outcomes and indicators of case mix.
      The core of the information system consists in a database of actors descriptions,
      and in an algorithm combining rules and data on Structures, Outcomes and Case mix
      to identify leaders. Results from the benchmark consist in the Processes of the
      leaders. An example using data from a surgical site infection surveillance
      network is provided. Actors were hospital surgical departments. Structure
      consisted in the type of the hospital, specialty and annual number of
      interventions. The algorithm for selection of leaders was implemented using a
      decision tree. Using this framework, benchmarking could be facilitated and more
      easily accepted by professionals.

PMID- 14664083
TI  - Simulation and management games for training command and control in emergencies.
AB  - The aim of our project was to introduce and implement simulation techniques in a
      problematic field of increasing health care system preparedness for disasters.
      This field was chosen as knowledge is gained by few experienced staff members who
      need to disperse it to others during the busy routine work of the system
      personnel. Knowledge management techniques ranging from classifying the current
      data, centralized organizational knowledge storage and using it for decision
      making and dispersing it through the organization--were used in this project. In
      the first stage we analyzed the current system of building a preparedness
      protocol (set of orders). We identified the pitfalls of changing personnel and
      loosing knowledge gained through lessons from local and national experience. For
      this stage we developed a database of resources and objects (casualties) to be
      used in the simulation in different possibilities. One of those was the
      differentiation between drills with trainer and those in front of computers
      enable to set the needed solution. The model rules for different scenarios of
      multi-casualty incidents from conventional warfare trauma to combined
      chemical/toxicological as well as, levels of care pre and inside hospitals--were
      incorporated to the database management system (we used Microsoft Access' DBMS).
      The hardware for management game was comprised of serial computers with network
      and possibility of projection of scenes. For prehospital phase the possibility of
      portable PC's and connections to central server was used to assess bidirectional
      flow of information. Simulation software (ARENA) and graphical interfase (Visual
      Basic, GUI) as shown in the attached figure. We hereby conclude that our system
      provides solutions which are in use in different levels of healthcare system to
      assess and improve management command and control for different scenarios of
      multi-casualty incidents.

PMID- 14664084
TI  - Evaluation of a web-based system for survival estimation in breast cancer.
AB  - OBJECTIVES: To evaluate the accuracy of an internet-based method for survival
      estimation in breast cancer. DESIGN: A website was created which allows the user
      to enter information on prognostic factors for a patient, and instantly obtain a
      Kaplan-Meler survival curve based on outcome data of prior cases with a matching
      prognostic factor profile. The source for the survival data is a Finnish
      nationwide series of 2,842 women diagnosed with breast cancer in 1991-2,
      comprising 91% of all cases within the selected geographical regions during these
      two years. MAIN OUTCOME MEASURES: The accuracy of the survival estimates obtained
      using data from the nationwide series was assessed in an independent, single
      institution validation series (n = 565), and measured by analysis of calibration
      and discrimination (the area under the ROC curve). RESULTS: A selection of
      prognostic factors recommended by the National Institutes of Health (NIH)
      Consensus Development Panel and the International Consensus Panel on the
      Treatment of Primary Breast Cancer were made available for case-matching on the
      website. Kaplan-Meier case-match eight-year estimates of distant disease-free
      survival (DDFS) based on combinations of tumour size, histologic grade and mode
      of detection (screen-detected vs. symptomatic) were close to the actual outcomes,
      e.g. patients in the validation set who were estimated to have a 71-80%, 81-90%
      and 96-100% DDFS had an actual average DDFS of 76%, 88%, and 100%, respectively.
      CONCLUSIONS: A web-based case-match system can generate survival curves for user
      defined prognostic factor combinations and identify patients with a varying risk
      for breast cancer recurrence. The system can be linked to other data sets,
      expanded to accommodate new prognostic factors and used as a source for
      population-based survival estimates.

PMID- 14664085
TI  - Impact of nursing education in Slovenia on nurses' publishing in their
      professional journal.
AB  - The paper discusses influences of developments in nursing education in Slovenia
      on the structure and contents of publications in the Slovene journal of the
      nursing profession--the Review of Nursing. Undergraduate nursing education in
      Slovenia changed from Associate Degree to Diploma level, while the B.S.N. type
      programme was of brief duration. Bibliometric data was gathered on all the
      scientific and technical papers published in the Review of Nursing between 1977
      and 2001. Statistical analyses were carried out to study characteristics and
      inter-relations of authorship, cited references and contents. A positive impact
      of improved and extended education of nurses on quantity and quality of their
      publications has been confirmed. The paper is part of a larger study on nursing
      education in Slovenia and its relation to the works published in the Review of
      Nursing.

PMID- 14664086
TI  - A platform to develop and to improve effectiveness of online computable
      guidelines.
AB  - The quality criteria of guidelines are identified. Taking these criteria into
      account we have built a platform to improve computable guideline effectiveness
      and facilitate their production. Our implementation is based on the GLIF Model
      (GuideLine Interchange Format). We have designed software components to edit,
      test, index, perform and present guidelines in a user-friendly Web architecture.
      These components are based on XML specifications in order to preserve their
      shareability and their re-usability. Several guidelines have been developed using
      our approach. We discuss the advantages of such an implementation and future
      evolutions so as to improve guideline integration within the clinician's
      workflow.

PMID- 14664087
TI  - Documenting nursing practice by using ICNP on the Web.
AB  - This paper presents the design and implementation of an internet based nursing
      care planning system which helps nursing professionals and students to study ICNP
      beta 2 version and to create nursing diagnoses, interventions and outcomes by
      selecting relevant terms from ICNP. This advanced web-based ICNP browser enables
      the authentication of the user, and the creation of a type of nursing care plan
      through the use of ICNP. It provides different ways for creating nursing
      diagnoses, interventions and outcomes, by selecting relevant ICNP terms through
      the tree-structure view, index and search components of the tool. The created
      diagnoses, interventions and outcomes are stored to a secured database. The
      system provides to the user the facility to build and manage nursing care plans
      by using both the English and the translated Greek ICNP versions. The first
      results of the implementation of this internet based nursing care planning system
      are presented.

PMID- 14664088
TI  - Nursing care nomenclatures: real implementation in the computerized patient care
      record.
AB  - We report our experience in the conception and the use of a detailed nursing care
      documentation electronic record. This nursing care record is completely
      nomenclature driven, including the user-interface. International nomenclatures or
      classifications such as NANDA are used. They have been translated to French and
      their language adopted to the local practice habits. This nursing CPR is used in
      nineteen wards in the five campuses of the University Hospitals of Geneva,
      covering a broad range of nursing care types, such as acute adult and paediatric
      care, surgery, general internal medicine, geriatrics, in- and outpatient
      psychiatry and long-term rehabilitation. This paper focuses on the problematic of
      the use of nomenclatures and classification in a nursing daily practice,
      particularly the social and behavioural challenges that had to be faced. The
      rationale behind the use of these nomenclatures is presented. We present some of
      the techniques that have been used to make a nomenclature-driven nursing CPR more
      attractive for nurses.

PMID- 14664089
TI  - Improving the DRG system in Hungary.
AB  - Handling cases should be a profitable endeavour for the hospitals, but high
      caseloads have them running in the red. The reason for this may very well be the
      way the weighting is structured in the DRG system. The current way of thinking is
      that the indirect costs of the hospital care must be distributed on the case's
      days and the average of the direct costs can be added into the calculation of the
      DRG class's weighting factor. A dissenting opinion calls for creating the total
      weight proportionally by the direct costs. This paper shows an alternative, which
      balances both opinions by implementing corrective measures for the DRG class
      weigh, and thus is able to make complicated cases profitable.

PMID- 14664090
TI  - Electronic discharge letters using the Clinical Document Architecture (CDA).
AB  - Communication between hospitals and general practitioners is often restricted to
      paper-based discharge letters. In order to meet the growing need for improved
      data communication between various actors in the healthcare domain, it is
      necessary to overcome the barriers of software heterogeneity and lack of
      standards. HL7's clinical document architecture (CDA) is a new tool to exchange
      clinical documents. In this paper we show how CDA can be used to share electronic
      discharge letters generated in the hospital information system with general
      practitioners. Ease-of-use and data security and integrity were the main design
      principles. Although there still remain technical and organizational issues to be
      solved, this is a promising method in order to enhance data exchange between
      hospital and primary care and to move towards an electronic patient record (EPR)
      crossing institutional borders.

PMID- 14664091
TI  - From DRG databases to an epidemiological observatory for colorectal cancer in a
      French small area oncology network.
AB  - Following a request from the local health authority, we have organised the
      permanent linkage of DRG/MBDS databases from different tertiary care hospitals
      from Saint-Etienne urban area. To made anonymous the MBDS, we used the asymmetric
      hashing and encrypting software developed and registered by the University
      hospital of Dijon. In each hospital, the selection of acute care stay MBDS is
      performed on the presence of at least one malignant tumour ICD code. The output
      is an anonymous but personal 20,000 patients register. We are presenting the
      method to estimate the incidence of colorectal cancer (CRC) cured between 1996
      and 2000 from DRG databases of four hospitals and checking the validity against
      the figures coming from a cancer registry. Among the 1953 CRC patients observed,
      156 patients have followed a CRC surgical excising in 1999. The DRG activity of
      the 4 observatory hospitals is 33.5% of the total hospital activity for people of
      the area recorded by the 1999 regional DRG PMSI data bases. The estimation of the
      incidence is 465 for 1999, the estimation of the same incidence by applying the
      incidence rate by sex and age from the Isere cancer register to the population of
      the Loire area, is 504. The under estimation is 7.7% with the observatory method.
      It is rather difficult to check an estimation by another estimation but in France
      the evaluation of oncology care strategies is impeded by the lack of cancer
      registries. The conclusion of this study is a good feasibility and acceptability
      of the linking procedure when used with a clear healthcare goal. The use of DRG
      data bases within an oncology network by linking the mandatory MBDS data bases
      gives the opportunity to share some clinical data between healthcare
      professionals.

PMID- 14664092
TI  - Establishing health informatics as a recognised and respected profession in the
      UK National Health Service.
AB  - The delivery of healthcare is an information dependent process. National
      government modernisation targets, and drives to improve the effectiveness and
      efficiency of care delivery systems and processes have the better use of
      information and IT at their heart. If we are to realise the benefits information
      and IT developments can bring, we have to ensure we have a suitable cadre of well
      educated, proactive professional specialists who understand the business of
      healthcare. The English NHS has an attrition rate of something like 43% amongst
      its ICT specialists, and there are recruitment and retention problems in a range
      of other informatics disciplines like medical records, project management and
      strategic management. A 1999-2000 survey indicated the reasons for recruitment
      and retention problems. One agreed solution has been to work towards establishing
      health informatics as a recognised and respected national profession. This is in
      addition to other national work to establish career pathways, make health
      informatics as a profession "mainstream", and to provide development
      opportunities at all levels. This paper sets out the background to the
      establishment of a profession in UK health services, outlines progress to date,
      and summarises other national development activity to support health informatics
      professionals.

PMID- 14664093
TI  - Health data management and strategic management in Brittany: some practical
      problems.
AB  - Recent changes in the organisation of the French health system include 1996's
      ordinances, and more recently (4th Law march 2002). The general tendency of all
      these reforms is the management of the health system at the regional level in
      France. In This paper we try to find how health data management systems could be
      concerned by this changes. In the first part we will explain why the health data
      management systems are implicated in theses changes. After that we specify the
      kind of information needed for strategic management of health at the regional
      level in Brittany. Then we discuss what information is available from all health
      data management systems at the regional level as far as decision making in health
      is concerned.

PMID- 14664094
TI  - The Danish National Health Informatics Strategy.
AB  - The central vision for the future information systems in the Danish health care
      sector is one of a generally accepted, common information model enabling
      comprehensive digital reuse of shared clinical data. A generic 'Basic-EHR
      structure' has been developed for this purpose by the National Board of Health
      from a through analysis of the production of clinical information. The strategy
      contributes to the achievement of the national political goals for the health
      care sector and describes four important steps to be made by the health care IT
      systems in order to reach full interoperability and digital reusability of
      clinical information. Some important initiatives of the strategy are a national
      terminology server, coordinated implementation of EHRs, and the Public Health
      Information Portal.

PMID- 14664095
TI  - Interchange of nominative patient data between health-care organizations.
AB  - In the context of current evolution of healthcare, hospitals will have to share
      medical files with different structures. Thus, it is necessary to establish
      procedures to identify the patients. A team professionals working with such
      medical information proposes a system of identification based on the matching of
      identification traits respecting various regulations in order to retrieve the
      information. We will see how this is made possible, with the help of a
      correlation engine enabling us to exchange medical documents between different
      health-care organizations.

PMID- 14664096
TI  - Improving the quality of communication in healthcare.
AB  - In this paper we present an assessment instrument for evaluating the quality of
      communication processes in health care. This instrument is based on communication
      theory, and does not only indicate the level of quality, but also explains it.
      This makes it also useful as a design tool in reorganising communication
      processes, in order to make them more effective. Such a tool is highly needed
      when Information and Communication Technology is applied in health care to
      support communication between professionals. The instrument is demonstrated for a
      case in multidisciplinary team care.

PMID- 14664097
TI  - Modeling interdependencies between business and communication processes in
      hospitals.
AB  - The optimization and redesign of business processes in hospitals is an important
      challenge for the hospital information management who has to design and implement
      a suitable HIS architecture. Nevertheless, there are no tools available
      specializing in modeling information-driven business processes and the
      consequences on the communication between information processing, tools.
      Therefore, we will present an approach which facilitates the representation and
      analysis of business processes and resulting communication processes between
      application components and their interdependencies. This approach aims not only
      to visualize those processes, but to also to evaluate if there are weaknesses
      concerning the information processing infrastructure which hinder the smooth
      implementation of the business processes.

PMID- 14664098
TI  - About the language of Hungarian discharge reports.
AB  - Concerning use of terminological systems translated to any particular language or
      computer assisted translation of patient records the daily medical language has
      to be taken into account rather than the pure academic language. The aim of this
      study to investigate the language of the diagnosis of the Hungarian hospital
      discharge reports. Word of collection of discharge diagnoses were categorised
      according to the language and form (normal words, abbreviations, acronyms). It
      was found that Latin is still a dominant, but the language is rather a mixture,
      where local jargon, non standardised abbreviations occur frequently. Some signs
      show, that discharge reports are not used primarily as a tool of communication of
      physicians, rather serve local administrative purposes.

PMID- 14664099
TI  - A strategy for system improvement and data processing in a national GP Sentinel
      Network.
AB  - This paper presents the results and strategies concerning the running of MediNET
      sentinel dispensaries network in Romania. MediNET stations network consists in
      100 computerized dispensaries all around the country, where doctors collect data
      from primary care and send it to a central server through Internet. The network
      is fully functional and the collection of data started. We present a low-cost
      solution for developing the system, the preliminary results of collected data,
      the strategy for improving and developing the system and the strategy for future
      data processing.

PMID- 14664100
TI  - Patient demands and the development of EHR systems.
AB  - Patient demands to the development and implementation of electronic health care
      records (EHR) are rarely considered in professional health informatics societies.
      This project has investigated the citizens' opinion in Denmark by means of a
      newly developed methodology "development space". A group of citizens form a lay
      panel and are briefed on the fundamental issues in the development and strategies
      for EHR. They confront an expert panel with a number of questions and on the
      basis of the answers they write a report. The results show that the citizens in
      the lay panel demanded clear answers to strategic, technical and attitudinal
      questions. They demonstrated an ability to see through relatively complex
      relations and formulate multifaceted opinions, which can add valuable input to
      the development and implementation process of EHR in the professional
      environments.

PMID- 14664101
TI  - Monitoring the development and diffusion of EHR systems in Denmark.
AB  - The Danish EHR Observatory has monitored Danish EHR projects for several years
      with respect to a number of parameters such as diffusion, diffusion rate,
      barriers and limitations, and experience gained. The results of the 2002
      monitoring reveal that investment in IT is relatively low and the diffusion rate
      is below the estimated level. The EHR projects gain a lot of valuable experience,
      but the coordination of evaluation results should be improved.

PMID- 14664102
TI  - From computerized patient records to national resource.
AB  - To help curb constantly rising costs of medical services, healthcare providers in
      Israel have been busy incorporating computerized patient record systems (CPR)
      into their organizations since the early 1990s. Our CPR based integrated system
      solutions (named Clicks) now serve over 90% of primary and secondary medical care
      professionals throughout the country, covering over 90% of the population across
      medical fields with all healthcare providers. Online verification of member
      rights, embedded business rules and medical protocols as well as Preventive
      Medical Assistance (PMA) rules are incorporated into the system. These, coupled
      by bi-directional communication to facilitate implementation and enforcement at
      all points of service and to transmit administrative and focal medical
      information, have created a firm foundation for carrying out the organization's
      cost control and expense management strategies. The CPR systems based on these
      underlying concepts and on token driven data entry methodology have transformed
      traditional medical work areas into virtually paperless environments. The
      enterprise wide solutions use dedicated viewports to address the needs and
      requirements of any medical field, user population and a wide range of medical
      facilities. Extensive data collection and detailed documentation are maintained
      universally at all points of service, for the entire patient population. Current
      applications, based on a distributed approach and local databases with
      communication to central systems for bi-directional transfer of information,
      gradually give way to unified databases located on central systems. Two concepts
      are being implemented: (a) MDC (Medical Data Core), which contains patients'
      focal medical data as transmitted from the local database at the physician's
      workstation, and (b) a complete centrally located database, where continuous
      communication is required from the physician's workstation to the central system,
      through dumb terminals. This concept entails massive investment in communication
      capacity and hardware and requires high reliability of all communication
      transactions at all times. MDC information by contrast does not require open
      communication lines around the clock, is communicated bi-directionally at
      predefined points in time or in the workflow, alleviating load and congestion on
      communication lines. In addition, access, retrieval and display of MDC
      information is done using standard browsing techniques under known protocols and
      requires no extra investment for these capabilities.

PMID- 14664103
TI  - Family transitions related to parental separation.

PMID- 14664104
TI  - Custody and access issues with children whose parents are separated or divorced.
AB  - This article discusses the effects of family breakdown--and the resulting issues
      of custody and access--on children. It explores trends in child custody and
      access and issues surrounding those trends, particularly in terms of the benefits
      and limitations of joint custody. It then identifies the contextual problems of
      family breakups (including the relative poverty experienced by mother-led
      families, the unreliability of financial support from fathers, the complications
      for children which result from step-parent figures, including serial partners of
      their parents, the implications of interparental conflict, the need to fully
      address suspicions and/or allegations of abuse by one parent against another, and
      the problem of Parental Alienation Syndrome). Typical responses of children to
      family breakup are then considered, including feelings of loss, guilt, and
      responsibility, and a sense of divided loyalties--particularly in light of
      intense or violent parental conflict. And finally, recommendations are made to
      minimize the detrimental effects of family breakup on children: (a) allowing
      children choice and flexibility, (b) exploring the benefits of mediation for
      families, (c) promoting parental co-operation, and (d) encouraging an ongoing
      relationship with the nonresidential parent.

PMID- 14664105
TI  - Parental separation from children who enter the child welfare system.
AB  - This paper addresses the continuing importance of family or origin to the child
      in forster care.  A brief review of relevant literature is reinforced by findings
      from a recent study, Looking After Children in Canada.  The authors argue both
      for the continuing importance of family and for the value of consulting the
      children themselves, as does the Looking After Children approach.  They suggest
      that family preservation does not necessarily depend on where one resides, but on
      a continuing set of relationships.

PMID- 14664106
TI  - [Mediation and adjustment of the rupture of the union: the impact of Quebec law
      on family mediation].
AB  - In September 1997, a new family mediation law came into force in Quebec. This law
      allows couples with children to be provided with the services of a professional
      mediator while their application for separation, divorce, child custody, spousal
      or child support is being negotiated and settled or an existing decision is being
      reviewed. This article presents and discusses the results of a study that
      compares the practices and results of family mediation under this law with the
      previous situation. According to the data, the law provides greater access to
      mediation for low-income couples.

PMID- 14664107
TI  - Parent education after separation: results from a multi-site study on best
      practices.
AB  - Although parent education after separation in Canada is relatively new, most
      provinces and territories now have some type of program that provides separating
      parents with information on their children's needs, co-parenting options, and
      strategies for improving communication. A 1999-2000 survey of parents in 10 such
      program sites throughout Canada: (a) demonstrates a high level of parent
      satisfaction with the programs, (b) chronicles benefits related to reduced
      conflict and improved child well-being 3 to 4 months following program
      attendance, and (c) identifies several implications for best practices. Results
      of this study suggest that parent education is but one program within a network
      of services needed to support both parents and children after separation.

PMID- 14664108
TI  - [The birth of a restructured family: qualitative analysis of discourse between
      adolescents].
AB  - This paper discusses a period in the life of a stepfamily that has not been
      widely studied until now: the period immediately preceding and immediately
      following the move towards a blended family. This period is studied from the
      viewpoint of adolescents living through it. Here, the blending of a family is
      examined as a family transition; its "paranormative" character brings up issues
      that pertain especially to the children's adjustment. Twenty-six semistructured
      interviews were carried out with adolescents between the ages of 11 and 17. Among
      the main results was the observation that 2 events in particular mark this
      transition: the announcement of future cohabitation and the cohabitation itself.

PMID- 14664109
TI  - Keeping in touch with children after separation: the point of view of fathers.
AB  - The amount of father-child contact after separation is closely linked to the
      probability that father fulfill their financial obligations towards their
      children. Determining the factors that encourage this contact is, therefore,
      crucial to the process of reducing the risk of poverty to which children of
      separated parents are exposed. Based on data collected from fathers at the 1995
      Canadian General Social Survey of the Family, this paper uses multi-level
      regression analysis to identify factors associated with higher levels of contact
      between fathers and children, including socio-demographic characteristics of
      children and fathers, variables associated with attitudes, and fathers'
      satisfaction with custody and access arrangements.

PMID- 14664110
TI  - [The quality of sibling relation who have experienced family transitions and
      those who have not].
AB  - In this study, similarities and differences in sibling relationships between
      children who have experienced family transitions and those who have not are
      examined. Comparisons are made between children who live in intact families,
      those whose parents have separated, and those who live in substitute care
      regarding the quality of their relationships with one of their siblings. More
      specifically, 4 dimensions describing the quality of sibling relationships are
      compared: Warmth/Closeness, Conflict, Relative Status/Power, and Rivalry (Furman
      & Buhrmester, 1985). The sample is made up of 3 groups of children (N = 158) aged
      between 8 and 12 years old: children living in intact families (n = 101),
      children who have experienced parental separation (n = 35), and children living
      in substitute care (n = 22). Results indicate differences on dimensions of
      Warmth/Closeness, Conflict, and Relative Status/Power. Different patterns of
      responses between the children who have experienced family transitions and those
      who have not are observed for the dimensions of Conflict and Power. The
      significant difference observed between the groups for the dimension of Warmth
      appears difficult to explain. Discussion of these results emphasizes the
      importance of the relationship between brothers and sisters experiencing family
      transition.

PMID- 14664111
TI  - [The development of conjugal dissatisfaction in the context of a restructured
      family].
AB  - What factors influence the quality of marital relationships in stepfamilies? How
      does marital dissatisfaction develop in these families, and what elements can
      help prevent it? These are the questions which this article tries to answer. We
      first identify three areas where difficulties occur: individual, relational, and
      social. By using Social Learning Theory, we then explain how the interaction of
      factors specific to these areas contributes to the development of marital
      dissatisfaction in remarried couples. Finally, 3 essential elements for
      preventing difficulties emerge from the analysis: (a) information, (b)
      communicative abilities and (c) support.

PMID- 14664112
TI  - [Between "step-grandparents" within the restructured family? Example of "step
      grandmothers"].
AB  - Very little attention has yet been paid to the place of grandparents and
      stepgrandparents within stepfamilies, even though this new kind of family
      organization highlights the complexity of kinship systems. Thanks to recent
      studies, grandparental functions are beginning to be better understood. Still, as
      we demonstrate, both the media and specialists in the field represent
      grandparents and stepgrandparents in stepfamilies in a reductive way. Then, using
      semi-directive interviews and examining the question of appellation, we discuss
      the specific identify of stepgrandmothers.

PMID- 14664113
TI  - [Investing to keep memories].

PMID- 14664114
TI  - [Surgery in superficial skin lesions (II of III). Procedure: technique
      preparation].
AB  - The authors make a detailed presentation about the steps to follow to ensure the
      patient is comfortable and that the execution of this technique is correct. The
      authors review the most important aspects, including asepsis and anesthesia, to
      prepare a wound for suturing and to make preparations for surgery. They also
      provide a brief description of the necessary surgical instruments and their
      characteristics.

PMID- 14664115
TI  - [Subcutaneous route in palliative care. Efficient alternative in drug
      administration in advanced oncologic patients].

PMID- 14664116
TI  - [Hydrocolloids and lubricating materials in the treatment of acute and chronic
      wounds].
AB  - The authors carry out a study on a dressing which associates hydrocolloids and a
      lubricating material, Vaseline, used on 28 patients who suffer from acute or
      chronic wounds having diverse etiologies. The authors evaluate the biological
      process through which each wound builds scar tissue, its tolerance, efficiency
      and degree of acceptance with results which are frankly positive. The data in
      this study for these parameters coincide with those of other research projects
      which have been carried out in France, Germany and the United Kingdom.

PMID- 14664117
TI  - [Fibromyalgia, or whole body pain].
AB  - Fibromyalgia is a rheumatic syndrome which is being recognized and diagnosed more
      often all the time. Its symptoms include a general state of pain not localized in
      the joints, combined with tremendous tiredness and sleep alterations. Although
      its exact etiology is still unknown, medical professionals speculate on the
      existence of multiple cause factors. Therefore, an integrated therapeutic
      treatment having the coordinated participation of medical professionals from
      different fields of expertise is necessary. Mental health professionals play an
      important role since it is proven the existence of psychological and socio
      psychological factors at the start, during the duration of and in the evolution
      of this syndrome.

PMID- 14664118
TI  - [Fibromyalgia. A challenge for this century].
AB  - Fibromyalgia is a challenge which requires a precise energetic treatment plan due
      to the socio-labor problems along with the clinical problems it causes.
      Apparently, the number of cases will be higher to hose traditionally declared
      which was 2 to 2.5% of the population. Some complex and sophisticated tests might
      be added to the diagnostic scheme to guarantee its validity while at the same
      time research projects which aim to improve treatment are based on the so-called
      hopeful pharmaceuticals. Subsequently, in order to reinforce the research and
      medical assistance facets related to the syndrome, some definite aid from the
      Public Administration is warranted.

PMID- 14664119
TI  - [Fibromyalgia. The cinderella of rheumatism].

PMID- 14664120
TI  - [Why are hospital emergencies used? Opinion of nursing professionals].
AB  - In this paper we identify the key elements in the use of emergency health
      facilities. Using the data collected from 14 nurses (5 individual interviews & 6
      from focal group), and following of Giorgi (1997) method, we found that those
      elements are: Changes in the Emergency Health concept, b) The lack of information
      and education about Health Facilities, c) The belief that Emergency Facilities
      are better than other kinds of health facilities, and d) The biasing influence of
      the media. We suggest analyzing the recipient's point of view.

PMID- 14664122
TI  - [Steam sterilization].

PMID- 14664121
TI  - [Cannabis. Analysis of the effects of cannabis on the body and nursing practice
      in detoxification].

PMID- 14664123
TI  - [Guide for identification of attitudes and skills].

PMID- 14664124
TI  - Bar-coded medication administration (BCMA) systems. Future promise, present
      challenges.
AB  - One popular new method for building safeguards into the medication administration
      process is the use of a bar-coded medication administration (BCMA) system.
      Clinician use the system's bar-code scanner to scan labels on the medication
      packaging and on the patient's identification wristband. In this way, the system
      verifies that administered medications match provider orders at the point of
      care. BCMA systems have received a lot of media attention and manufacturer
      promotion. However, they aren't yet a practical option for most hospitals.
      Although they offer great potential to help prevent administration errors,
      current systems have significant limitations. To realize maximum patient safety
      benefit, an ideal BCMA system should be capable of both point-of-care medication
      verification and automatic programming of infusion pumps. No current system
      offers both capabilities. In this article, we discuss these and other limitations
      and list objectives that need to be met to make commercial BCMA systems
      successful. We also give advice to help hospitals reduce medication error now and
      prepare for future implementation of integrated BCMA systems.

PMID- 14664125
TI  - General-purpose infusion pumps. Evaluating the B. Braun Outlook Safety Infusion
      System.
AB  - General-purpose infusion pumps deliver liquid medications and intravenous (i.v.)
      fluids to patients through i.v. or epidural routes at specified flows. They are
      most often used when greater accuracy or higher flows are needed than can be
      provided by a manually adjusted gravity administration set. In this Evaluation
      (which updates our October 2002 study), we present our findings for two newly
      evaluated pumps: the B. Braun Outlook 100 and Outlook 200. The Outlook 200 is the
      first general-purpose infusion pump to offer a new type of safety feature: an
      automated programming system. This system scans bar-coded labels on i.v. fluid
      containers and on patient (and sometimes clinician) identification and
      automatically programs this information into the pump. Unfortunately, the 200's
      system has not yet been successfully implemented in a clinical setting.

PMID- 14664126
TI  - ECRI's latest audio conference targets surgical fires. Training and communication
      are key, say speakers.

PMID- 14664127
TI  - Using the wrong power converter or battery charger can injure staff and damage
      equipment.

PMID- 14664128
TI  - Adapter connecting HP CodeMaster defibrillators with Philips HeartStart paddles
      and pads could delay defibrillation.

PMID- 14664129
TI  - Judging dose error reduction systems.

PMID- 14664130
TI  - Torsion of the left ventricle during pacing with MRI tagging.
AB  - The effects of different pacing protocols on left ventricular (LV) torsion were
      evaluated over the full cardiac cycle. A systolic and diastolic series of
      magnetic resonance imaging (MRI) scans were combined and used to calculate the
      torsion of the LV in a canine model. The asynchronous activation resulting from
      ventricular pacing interferes with the temporal evolution of LV torsion. The
      torsion of the left ventricle was investigated under three different protocols:
      1) right atrial pacing, 2) right ventricular pacing, and 3) simultaneous pacing
      from the right ventricular apex and LV base. The temporal evolution of torsion
      was determined from tagged MRI and evaluated over the cardiac cycle. The peak
      rotation for the atrially paced hearts was 11.1 degrees (+/- 3.5 degrees)
      compared to 6.1 degrees (+/- 1.7 degrees) and 6.1 degrees (+/- 0.7 degree) for
      those hearts paced from the right ventricle and from both ventricles,
      respectively. While biventricular pacing increases the synchrony of contraction,
      it significantly alters the pattern of LV torsion. From these experiments we have
      shown that measuring torsion is an extremely sensitive indicator of the existence
      of ectopic excitation.

PMID- 14664131
TI  - Rapid-motion-perception based cardiac navigators: using the high flow blood
      volume as a marker for the position of the heart.
AB  - Navigators have been developed as one of the many approaches to reducing motion
      artifacts due to respiration. A typical navigator approach applies a pencil-beam
      style profile crossing the diaphragm to track the superior-inferior (SI) motion
      of the diaphragm, and subsequently applying correlations to determine the heart
      location. This approach necessitates a priori knowledge of the correlation
      coefficients between heart and diaphragm motion, a variable parameter among
      patients. This paper presents an alternative navigator method based on Rapid
      Motion Perception (RaMP). This method acquires profiles of the ventricular blood
      volume based on its high flow velocity. The position of the blood volume is a
      direct representation of the position of the heart. This method allows cardiac
      navigation in two orthogonal directions simultaneously, eliminates the need to
      obtain correlations to the diaphragm motion, and increases tracking reliability
      for individual patients. A prospective version of RaMP navigators has been
      implemented on a clinical 1.5 T scanner, and preliminary tests on human
      volunteers show that this method can successfully track the heart position over
      the entire respiratory period. This navigation scheme is tested for predicting
      superior-inferior and anterior-posterior (AP) motion of the heart for breath-hold
      and free breathing conditions. Bland-Altman plots comparing the motion predicted
      by the navigators and that computed from single-shot images immediately following
      the navigators, show that the accuracy of this method is +/- 1.43 mm in the SI
      direction and +/- 0.84 mm in the AP direction. The RaMP navigator is suited for
      real-time tracking of the bulk translational motion of the heart.

PMID- 14664132
TI  - Contrast-enhanced MRA and 3D visualization of pulmonary venous anatomy to assist
      radiofrequency catheter ablation.
AB  - In pulmonary vein isolation as a treatment for atrial fibrillation the proximal
      part of the pulmonary veins is catheterized. A protocol for preinterventional
      assessment of pulmonary vein anatomy was developed, based on contrast-enhanced
      magnetic resonance angiography (MRA) in combination with three-dimensional
      visualization to tailor periprocedural angiography. The results allow for
      assessment of the number, morphology, and location of the ostia of the pulmonary
      veins, as well as complicating anatomical variations, such as common trunks and
      aberrant courses.

PMID- 14664133
TI  - Myocardial mass and volume measurement of hypertrophic left ventricles by MRI-
      study in dialysis patients examined before and after dialysis.
AB  - Techniques to reliably quantify left ventricular myocardial mass (LVMM) are
      mandatory for monitoring therapy in patients with left ventricular hypertrophy
      (LVH). The purpose of this study was to measure LVMM and volumes by cine magnetic
      resonance imaging (MRI), and to assess acute changes through hemodialysis as a
      model for different loading states. Seven dialysis patients with LVH were
      examined before and immediately after hemodialysis. All MR imaging was done with
      a steady-state free precession (SSFP) cine sequence (TrueFISP; TR, 3.2 ms; TE,
      1.6 ms; flip angle, 60 degrees; slice thickness, 8 mm). LV volumes, ejection
      fraction (EF), and LVMM were determined by slice summation after manual
      planimetry in short axes. A significant reduction of end-diastolic volume (EDV)
      (mean pre, 140 mL; post, 109 mL; p < 0.01), end-systolic volume (ESV) (49 mL-->42
      mL; p < 0.05), and stroke volume (91 mL-->66 mL; p < 0.01) through dialysis was
      revealed by MRI. Ejection fraction did not change significantly. A slight
      decrease in LVMM was detected in all patients (mean pre, 184 g; post, 177 g; p <
      0.05). Intra- and interobserver variability for EDV, ESV, and LVMM were 1.3 +/-
      6.2 mL, -0.9 +/- 4.1 mL, -1.4 +/- 3.9 g, and 3.3 +/- 7.5 mL, 2.6 +/- 5.0 mL, -2.4
      +/- 4.6 g, respectively. Standard error of estimation (SEE) was +/- 2.3 mL, +/-
      2.0 mL, +/- 1.6 g, and +/- 2.6 mL, +/- 2.1 mL, and +/- 2.0 g for intra- and
      interobserver variability. In conclusion, cine MRI is a reliable technique for
      LVMM measurement that is independent of LV loading status. This method allows for
      detection of small changes, which is crucial for accurate therapy monitoring in
      LVH. Left ventricular myocardial mass and volumes decrease significantly during
      hemodialysis.

PMID- 14664134
TI  - Prediction of regional functional recovery after acute myocardial infarction with
      low dose dobutamine stress cine MR imaging and contrast enhanced MR imaging.
AB  - PURPOSE: Previous studies demonstrated that low-dose dobutamine stress cine
      magnetic resonance imaging (MRI) and delayed contrast-enhanced MRI can provide
      assessments of myocardial viability. The purpose of this study was to evaluate
      the comparative diagnostic values of dobutamine cine MRI and delayed contrast
      enhanced MRI for predicting functional recovery of myocardial contraction in
      patients with acute reperfused myocardial infarction. METHODS: Twenty-three
      patients with myocardial infarction after percutaneous coronary interventions
      were studied. All patients underwent steady-state cine MRI covering the entire
      left ventricle at rest and during low-dose dobutamine stress (10
      micrograms/kg/min). Delayed contrast-enhanced MR images were acquired to
      determine transmural extent of hyperenhancement. Second cine MR images in the
      resting state were obtained 3 to 11 months after revascularization. RESULTS: On
      the first cine MR images in the resting state, 278 (20%) of 1380 segments
      demonstrated abnormal, regional contraction (systolic wall thickening < 40%). Of
      the 175 segments showing functional recovery on the following cine MRI, 156 (89%)
      segments were recognized as reversible by dobutamine cine MRI and 146 (83%)
      segments by delayed contrast-enhanced MRI. The sensitivity, specificity, and
      accuracy of dobutamine stress cine MRI was 89%, 80%, and 86%, respectively. These
      values of contrast-enhanced MRI were 83%, 72%, and 79%, respectively. The area
      under the receiver operating curve (ROC) was 0.87 by dobutamine cine MRI and 0.78
      by delayed contrast-enhanced MRI (p < 0.05). CONCLUSIONS: The current results
      using quantitative segmental analysis indicated that low-dose dobutamine stress
      cine MRI can predict recovery of myocardial contractility with significantly
      higher diagnostic performance in comparison with contrast-enhanced MRI in
      patients with myocardial infarction who underwent revascularization.

PMID- 14664135
TI  - Optimal acquisition parameters for contrast enhanced magnetic resonance imaging
      after chronic myocardial infarction.
AB  - The aim of this study was to simplify the imaging of myocardial infarction based
      on theoretical aspects and patient variables and to define the optimal time for
      image acquisition. Thirteen patients with chronic myocardial infarction underwent
      magnetic resonance imaging. After injection of 0.2 mmol/kg body weight Gd-DTPA an
      inversion recovery turbo gradient echo sequence with different prepulse delays
      was applied every 3 to 5 minutes within an interval of 3 to 30 minutes. As
      parameters of investigation, the area of signal enhancement and the contrast
      between enhanced and nonenhanced myocardium were used. There was no influence of
      prepulse delay or time after contrast injection on the enhanced area. The
      contrast between enhanced and normal myocardium showed a peak at 6 minutes post
      Gd-DTPA injection and remained high. The contrast between blood and enhanced
      myocardium was best at 6 and 25 minutes with best intra- and interobserver
      variability. In conclusion, if a suitable contrast was achieved, the area of
      enhancement is independent of prepulse delay or imaging time. In most patients
      the highest contrast between blood, enhanced and normal myocardium is achieved 6
      minutes and 25 minutes after contrast injection.

PMID- 14664136
TI  - Initial experiences with in vivo right coronary artery human MR vessel wall
      imaging at 3 tesla.
AB  - Due to their relatively small size and central location within the thorax,
      improvement in signal-to-noise (SNR) is of paramount importance for in vivo
      coronary vessel wall imaging. Thus, with higher field strengths, coronary vessel
      wall imaging is likely to benefit from the expected "near linear" proportional
      gain in SNR. In this study, we demonstrate the feasibility of in vivo human high
      field (3 T) coronary vessel wall imaging using a free-breathing black blood fast
      gradient echo technique with respiratory navigator gating and real-time motion
      correction. With the broader availability of more SNR efficient fast spin echo
      and spiral techniques, further improvements can be expected.

PMID- 14664137
TI  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors improve myocardial
      high-energy phosphate metabolism in men.
AB  - PURPOSE: We intended to prove that 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors or statins have a beneficial impact on the human myocardial,
      high-energy, phosphate metabolism. METHODS: The present study included 18 male
      patients (mean age 49.8 +/- 10.3) with statin-treated, familiar
      hypercholesterolemia (FH) and 13 male patients with untreated FH (mean age 44.6
      +/- 9.5). Twenty-six healthy male volunteers served as controls (mean age 44.2 +/
      12.1). Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the
      heart was performed in all subjects using a 1.5 Tesla whole-body magnetic
      resonance (MR) scanner. The ratios between phosphocreatine (PCr) and beta
      adenosine-triphosphate (beta-ATP) were calculated for the left ventricular
      myocardium. Furthermore, echocardiographic evaluation and stress tests were
      performed in all individuals. RESULTS: The untreated patients with FH exhibited a
      significant decrease in left ventricular PCr to beta-ATP ratios (1.78 +/- 0.34)
      compared with statin-treated FH patients (2.15 +/- 0.26, p < 0.001) and healthy
      controls (2.04 +/- 0.26, p = 0.009). The left ventricular PCr-to-beta-ATP ratios
      of the treated FH patients were in the range of the healthy controls.
      CONCLUSIONS: Our study shows for the first time an-improvement of the high
      energy, phosphate metabolism in the left ventricular myocardium of patients with
      statin-treated FH compared with untreated FH patients.

PMID- 14664138
TI  - [Bone tumors: classification, nomenclature, diagnostic problems].
AB  - Main principles of current classification and nomenclature of bone tumours and
      tumour-like lesions are presented. Association of pathological processes in the
      skeletons with functional features of certain anatomophysiological zones and
      processes of skeleton growth acceleration is shown. Main principles of bone
      tumours diagnosis are formulated and difficulties associated with lack of
      clinical information are outlined.

PMID- 14664139
TI  - [MALT gastric lymphoma--principles of morphological diagnosis].
AB  - MALT gastric lymphoma presents difficulties for morphological diagnosis as it is
      represented by neoplastic elements having morphology of mature cells. 75 MALT
      lymphomas of the stomach with polymorphous tumour infiltrate are reported. The
      infiltrate was analyzed by cell composition, cell atypia, the presence of
      lymphoepithelial lesions (LEL) and lymphoid follicles, blast cells and "blast"
      LEL. Immunohistochemistry may be necessary for diagnosis when clear-cut
      morphological characteristics are lacking.

PMID- 14664140
TI  - [Expression of nm23 and c-erbB-2 proteins in cells of primary colorectal cancer
      and its metastases].
AB  - Expression of proteins nm 23 and c-erbB-2 is observed in many human carcinomas
      and is associated with the disease progression. Immunohistochemical study of nm23
      and c-erbB-2 expression was performed on 64 primary tumours, 19 metastases in the
      lymph nodes and 37 liver metastases. More pronounced expression of these proteins
      in the primary tumour cells is observed in cases with liver metastases.
      Expression of nm 23 was observed in 66% and that of c-erbB2 in 59% of liver
      metastases. Thus, expression of these proteins may reflect biological behaviour
      of the tumour and may appear to be an important factor in development of
      colorectal cancer metastases.

PMID- 14664141
TI  - [Peculiarities of E-cadherin, mucin-2, and Ki-67 expression in colon
      adenocarcinoma].
AB  - E-kadherin, MUC2 and Ki67 expression was studied in colon adenocarcinomas of
      various differentiation. A direct relationship was detected between
      characteristics of expression of E-kadherin, MUC2 and the degree of
      differentiation as well as metastatic potential of the tumours.

PMID- 14664142
TI  - [Iliac mucosa changes in late periods after total colectomy in patients with
      syndromes of gastro-intestinal polyposis].
AB  - We studied follow-up iliac mucosa biopsies from 11 patients with juvenile
      polyposis and 4 patients with familial adenomatous polyposis who had undergone
      total colectomy with mucosal proctoectomy with creation of straight ileoanal
      anastomosis. The biopsies that have been taken from the posterior wall of the
      terminal ileum show incomplete and focal neocolonic transformation of iliac
      mucosa. Nevertheless, in most cases iliac mucosa preserved its architectural and
      histochemical characteristics. Chronic inflammation in iliac mucosa is not
      typical for patients with polyposis.

PMID- 14664143
TI  - [Role of matrix metalloproteinase-2 and components of the extracellular matrix-
      collagen type IV and laminin expression in detection of the invasive potential of
      pancreatic tumors].
AB  - Invasive potential of ductal tumors (adenocarcinoma, mucinous-cystic tumors,
      gastrinoma and undifferentiated tumors) positively correlated with the degree of
      metalloproteinase-2 expression and negatively correlated with stromal content of
      type IV collagen.

PMID- 14664144
TI  - [Her-2/neu, Ki-67 expression and ploidy in breast carcinoma].
AB  - Expression of the markers was studied immunocytochemically on cytological
      preparations of breast tumor, ploidy was assessed by flow cytofluorimetry. The
      material was divided into 2 groups: diploid--41.4% cases and aneuploid--58.6%.
      Hyperexpression of Her-2/neu in the first group was observed in 54.5%, in the 2nd
      group in 48.6% cases. Expression of Ki-67 in 63.4% and in 68.9%, respectively.
      Tumours with high proliferative activity were numerous in aneuploid tissues, and
      in diploid tumours moderate activity prevailed (p = 0.006). Direct correlation
      between the markers was observed, high expression of Ki-67 more frequently was
      associated with positive expression of Her-2/neu. Thus, aneuploid tumours with
      high proliferative activity and hyperexpression of Her-2/neu are more aggressive
      tumours of a large size.

PMID- 14664145
TI  - [Morphometrical and immunohistochemical criteria of prognosis in patients with
      serous and mucinous ovarian carcinoma].
AB  - The aim of the study was to investigate the prognostic value of morphometrical
      features and expression of receptors to progesterone in malignant epithelial
      ovarian tumours. Surgical biopsy materials of 92 patients with serous and
      mucinous ovarian cancer were investigated. Tissues stained by hematoxilin and
      eosin were studied. Morphometry was performed with computer program Axio Vision
      3.0. Immunohistochemical characteristics were evaluated with monoclonal
      progesterone antibodies. It was found that cytomorphometrical features vary in
      ovarian cancer with different histological structures and the level of
      differentiation of tumour, and can be used as prognostic factors. We revealed
      correlation between cytomorphometric factors (carcinoma cell area, total nuclear
      area, roundness of cell) and risk of recurrences and metastatic spread. In serous
      cancers presence of progesterone receptors is a favorable factor of prognosis
      and, as a rule, associates with a high degree of tumour differentiation. In this
      group of patients 3-year survival reached almost 100% indicating the efficiency
      of hormonotherapy and chemotherapy.

PMID- 14664146
TI  - [Importance of urgent histological investigation in surgical treatment of
      biliopancreatoduodenal zone carcinoma].
AB  - Urgent intraoperative investigation allows a surgeon, depending on the
      morphological conclusion, to conduct individual surgical intervention in the form
      of anastomosis with penetration into the tissue of the pancreas. The method
      decreases the rate of surgical complications, improves immediate results of
      patient treatment and reduces postoperative lethality. This proves the importance
      of morphology in the surgical treatment of tumours in the zone concerned.

PMID- 14664147
TI  - [Atypical adenomatous hyperplasia and dysplasia in squamous epithelium of the
      honeycomb lung in outcome of idiopathic fibrosing alveolitis].
AB  - Relationships between sclerosis and carcinogenesis in the honeycomb lung were
      studied in the outcome of two variants of idiopathic fibrosing alveolitis (IFA)
      common interstitial pneumonia (CIP) and desquamative interstitial pneumonia (DIP)
      which may be a background for lung carcinoma development. The material was
      obtained from 43 patients with the diagnosis of IFA. Immunohistochemically were
      studied: TNF-alpha (DAKO, Denmark, 1:100), pancytokeratines (Immunotech, Germany,
      concentration 1:100), Ki67 (DAKO, Denmark, 1:40), TGF-beta (Biosource
      international, USA, 1:100), CD34 (Novocastra, Great Britain, 1:100), EMA (DAKO,
      Denmark, 1:100). Differences in morphogenesis of CIP and DIP were found. CIP is
      characterised by primary pronounced lung interstitium damage with stroma
      vascularisation already at early stages with secondary involvement of the
      epithelium with development of adenomatous hyperplasia with or without atypia
      which is usually observed at the stage of lung honeycomb. Pronounced primary
      damage of alveolar epithelium as a result of action of activated alveolar
      macrophages with subsequent proliferation, desquamation and squamous epithelium
      metaplasia were more typical for DIP. The presence of squamous meta- and
      dysplasia of the epithelium is characteristic for DIP outcome in the honeycomb
      lung.

PMID- 14664148
TI  - [Comparison of the indices of occurrence of the diagnoses as a method of
      assessing the quality of histological diagnostics (using intraepithelial and
      invasive uterine tumors as an example)].
AB  - The method of comparison of frequency of intraepithelial and invasive tumours
      established on biopsy and surgical material of uterine cervix and body is
      proposed. The frequency of invasive and intraepithelial tumours of uterine cervix
      in different anatomo-pathological cervices of general profile was 0.8-5.3% and
      1.5-42.7% respectively, those of uterine body 0.2-2.2% and 0-2.3%. Frequency of
      uterine body tumour diagnoses was significantly higher at the age over 40 years.
      As a control of frequency it is suggested to consider maximum diagnoses at
      minimum level of errors: 8.4 +/- 2.2% diagnoses of intraepithelial and invasive
      tumours of the uterine cervix and 1.5 +/- 0.7% (2.1 +/- 1.1% in patients over 40
      years)--of uterine body.

PMID- 14664149
TI  - [Clear-cell odontogenic carcinoma].
AB  - The tumor of the mandible in this case was first qualified as ameloblastoma.
      Although in the last WHO classification clear-cell odontogenic tumour is
      considered to be a benign tumour, repeated recurrences and distant metastases
      described in the literature prove its malignant character.

PMID- 14664150
TI  - [Establishment of pathoanatomic service in Rostov-on-Don and North-Caucasus
      region].

PMID- 14664151
TI  - [The 70th anniversary of the department of pathologic anatomy of the Ivanovo
      State Medical Academy].

PMID- 14664152
TI  - [Petr Petrovich Erofeev (1903-2003)].

PMID- 14664153
TI  - [Perinatal anatomopathological diagnosis].
AB  - The authors propose a synthetic scheme of perinatal anatomo-pathological
      diagnosis which, on the one hand, contains conventional concepts of wide
      interpretation of basic disease in mono-, bi- and multicausal genesis of the
      disease and death and, on the other hand, the order of placing clinical data
      about mother's diseases, complications of pregnancy and delivery, information
      about external causes of the child's (fetus's) death and placenta pathology.
      Nosological characteristics of "Single states arising in perinatal period" (class
      XVI, POO-P96 rubrics) are presented and 10 principles of their uniform
      explanation in documentation of perinatal anatomo-pathological diagnosis are
      formulated.

PMID- 14664154
TI  - [Some problems of anatomopathological diagnosis in perinatology].
AB  - The authors discuss the problems of adequate documentation of autopsy diagnosis
      in death of fetuses and newborns and relations to ICD-10. It is suggested to
      legitimize and perfect the structure of diagnosis in perinatology.

PMID- 14664155
TI  - [The mechanisms of horizontal gene transfer: the role of bacteriophages and
      integrons in the evolution of pathogenic bacteria].
AB  - The role of bacteriophages, e.g. filamentous phages, whose single-stranded DNA
      comprise the coding virulence factors, as well as of certain suspected
      bacteriophage derivatives like constin-elements, integrons and chromosomal super
      integron, played by them in the horizontal gene transfer and in the evolution of
      bacteria is under discussion.

PMID- 14664156
TI  - [The pro-dependent folding of microbial proteolytic enzymes].
AB  - Modern published data on the folding of microbial proteolytic enzymes mediated
      through their pro-parts, or on a so-called pro-dependent folding, are surveyed.
      Various aspects related with the functioning of pro-sequences are under
      discussion. The possibility to build up, on the basis of one and the same amino
      acid sequence, the special protein conformers involving different pro-peptides is
      in the focus of attention.

PMID- 14664157
TI  - [Clinical strains of Burkholderia cepacia: characteristic and detection of the
      components in the quorum sensing regulatory system].
AB  - Described in the paper are characteristics of B. cepacia clinical strains
      isolated from patients at Moscow hospitals. The strains were investigated for the
      presence of proteolytic, chitinolytic, hemolytic and lipase activities as well as
      for presence of components of the "Quorum sensing" gene activity regulatory
      system by using biological test-systems and in the polymerase chain reaction with
      primers to genes cepI and cepR.

PMID- 14664158
TI  - [Production and characterization of a panel of monoclonal antibodies to
      Toxoplasma gondii antigens].
AB  - A representative collection was obtained containing 68 monoclonal antibodies
      (MAB) to Toxoplasma gondii antigens, which was characterized by the binding with
      the below fractions of tochizoites in the immune-enzyme assay (IEA) and
      immunoblotting (IB): membrane (MEM), somatic (water-soluble, SOM) and excretory
      secretory (ES). Most of MABs were produced to MEM antigens (43), 6 MABs reacted
      with the somatic fraction, and 3 MABs reacted with both fractions. Two MABs to ES
      antigen were detected in the latter group. An analysis of MABs in concurrent IEA
      and IB revealed the immune-dominant proteins of the MEM and SOM fractions of
      antibodies to T. gondii tochizoites (p30 and p27, respectively). The presence of
      2 non-overlapping antigenic determinants was shown for p30. Further research
      would detect MABs that could be used in the diagnosis of toxoplasmosis.

PMID- 14664159
TI  - [Identification of Mycobacterium tuberculosis strains and a simultaneous
      identification of their drug resistance by the hybridization method on
      oligonucleotide microchips].
AB  - A method of multiplex polymerase chain reaction (PCR) with subsequent
      hyoridization on oligonucleotide microchips was worked out to identify the
      Mycobacterium tuberculosis complex and to determine simultaneously the bacterial
      sensitivity to 2 first-line drugs, i.e. rifampin and isoniazid. The method
      provides for detecting above 95% of rifampin-resistant and around 80% of
      isoniazid-resistant strains within 1 day.

PMID- 14664160
TI  - [Molecular-genetic comparison of morbilliviruses which caused epizooty in Baikal
      (Phoca siberica) and Caspian (Phoca caspica) seals].
AB  - The nucleotide sequences were determined for a phosphoprotein gene fragment of
      canine distemper virus (CDV) by using the RT-PCR method with the subsequent
      sequencing of amplicons from total RNA isolated from 2 samples of Caspian seals,
      15 samples of Baikal seals and from samples of dog's and sea-lion's brains. The
      above materials were phylogenetically analyzed. The heterogeneity of the virus
      circulating in the Baikal-seal population was demonstrated. Morbillivirus, that
      caused epizooty in Caspian seals, was shown to be a CDV variant, whose
      phosphoprotein gene structure was not different, within the analyzed stretch,
      from the corresponding gene of the most widespread variant of the Baikal seal
      virus. The data obtained suggest that morbillivirus could be transmitted by birds
      during their seasonal migrations.

PMID- 14664161
TI  - [The induction of neovascularization in chorioallantoic membrane of chicken
      embryos transfected by a recombinant plasmid containing human angiogenin gene].
AB  - A method was elaborated to evaluate the biological activity of expression
      products of gene in the plasmid vectors, which are crucial for the synthesis of
      growth factor of blood vessels. It was proven as possible that the
      chrioallantonic membrane (CAM) of chicken's embryos could be transfected by
      recombinant plasmids containing both the reporter and target genes. The
      efficiency of CAM transfection was assessed by a plasmid carrying the reporter
      gene of green fluorescent protein (GFP). Finally, it was demonstrated that, at an
      infiltration of the recombinant plasmid containing the human angiogenine gene,
      its expression products induce the neovascularization in the CAM cells of
      chicken's embryos and stimulate an accretion in vessels of the 1st, 2nd and 3d
      orders.

PMID- 14664162
TI  - [Laminin-binding protein (LBP) as a cellular receptor for the virus of Venezuelan
      equine encephalomyelitis (VEE): Part 1. A study of the interaction between VEE
      virus virions and the human recombinant LBP].
AB  - The interaction of the VEE virus virions with human LBP was investigated. The
      affinely purified 43 kDa recombinant LBP (rLBP) of man was found to interact
      effectively with the VEE virus virions purified in immune enzyme assay. The
      affinity constant of 43 kDa rLBP with virions was equal to 4.3-4.8 x 10(7) M-1.
      The rabbit antiviral polyclonal antibodies blocked the interaction of rLBP with
      the VEE virus virions. According to Western blot, rLBP is capable of interacting
      with the E1 glycoprotein of the VEE virus, which suggests the presence of a
      specific epitope of binding with LBP in the surface of the E1-E2 heterodimer of
      the VEE virus. The results confirm that human LBP could be a receptor for the VEE
      virus.

PMID- 14664163
TI  - [Extracardiac manifestations of undifferentiated connective tissue dysplasia].
AB  - Undifferentiated connective tissue dysplasia (UDCTD) is a common type of
      congenital mesenchymal defect. Among the visceral manifestations of UDCTD,
      cardiac anomalies have been studied in detail while the nature, extent, and
      clinical significance of changes in other viscera are much less known. The review
      summaries data on currently accepted extracardiac manifestations of UDCTD, such
      as venous insufficiency, tracheobronchial dyskinesia, nephroptosis, genital
      prolapse, gastrointestinal disorders, hemostatic pathology.

PMID- 14664164
TI  - [Bronchial asthma and pregnancy].
AB  - The review of the data available in the literature dedicated to the problems of
      the diagnosis, clinical picture, and treatment of bronchial asthma (BA) in
      females during pregnancy. BA is shown to belong to the diseases whose pattern
      changes during pregnancy and despite that there are a great deal of papers on the
      above problem, the genesis of these changes has not been determined. Asthmatic
      attacks during gestation exert a significant negative impact on the development
      of pregnancy and the fetus; its main cause is hypoxia; however, there is no
      unambiguous evidence for this; today there are available several hypotheses that
      are presented in this paper. The data available in the literature show that most
      investigators consider it necessary to perform medical treatment for these
      disease; however, its nature has not been defined yet.

PMID- 14664165
TI  - [Hepatotoxic effects of drugs from some pharmacological groups].
AB  - The review presents the results of clinical-observations of side hepatotoxic
      effects of drugs from different pharmacological groups. Based on the data
      available in the literature, the authors systematized and supplemented the
      characteristic types of hepatic damages due to the use of drugs in different
      fields of medicine. The basic mechanisms responsible for the damaging effects of
      hepatotropic pharmacological agents are considered. The review places a
      particular emphasis on the major hepatic dysfunctions observed in oncological
      care when antitumor drugs having different mechanisms of action. This section of
      the review is supplemented with cases observed in the past years, wherein there
      are data on the hepatotoxicity of agents from the platin group, the nonsteroidal
      antiandrogen flutamide, topoisomerase II inhibitors in addition to the well-known
      alkylating drugs and antitumor antibiotics that have hepatotoxic properties.

PMID- 14664166
TI  - [Daily blood pressure profile in patients with hypertensive encephalopathy].
AB  - The purpose of the study was to study daily variations of blood pressure (BP) in
      patients with hypertensive encephalopathy (HE). Daily BP monitoring (DBPM) was
      made in 100 patients with different stages of HE. In HE, a proportion of patients
      from a non-dippers group substantially increased. An excessive nocturnal
      reduction in systolic BP (SBP) was more common. A dippers group was predominant
      in the controls. The daily index for SBP significantly decreased in patients with
      stage I HE; that for diastolic BP (DBP) reduced in those with stages I-II HE. The
      morning increase rate (MIC) of BP was studied. MIC of SBP was higher in patients
      with HE, which was most commonly observed in the non-dippers group. There was a
      more significant reduction in DBP in combination with high MIC in 10% of the
      examinees.

PMID- 14664167
TI  - [Arterial hypertension in menopausal women: Clinical, functional, and pharmaco
      economical aspects].
AB  - The study was undertaken to define the specific features of daily variations of
      blood pressure (BP) and autonomic cardiac regulation (ACR), as well as the
      functional status of the myocardium and vascular endothelium in females with
      menopausal arterial hypertension (MPAH) and to assess the pharmacotherapeutic and
      economical aspects of the combined use of arifon retard and clinonorm. The study
      enrolled 30 reproductive females with mild and moderate arterial hypertension
      (AH) and 65 females with MPAH who were randomly divided into 2 groups according
      to the therapeutic model. MPAH was characterized by more unfavorable hemodynamic
      changes that AH in the presence of preserved fertile function: greater load on
      target organs, elevated BP, its inadequate nocturnal lowering, greater BP
      variations, the magnitude and rate of its morning elevation. In AH, the vasomotor
      function of the endothelium varies with the clinical form of the disease and with
      the functional status of the female reproductive system. By and large, in the
      group of patients with MPAH, the latter was characterized by a more significant
      decrease in endothelium-dependent vasodilation (EDVD). Arifon retard monotherapy
      has an adequate antihypertensive effect in female patients with MPAH, by ensuring
      24-hour control of BP and affecting its chronostructure. A combination of arifon
      retard and climonorm has no cumulative effect on the level of BP and on the
      parameters of pressure-induced load; however, this is a pathogenetically grounded
      combination that potentiates the positive effects of a diuretic in significantly
      improving EDVD and ACR. The use of arifon retard in combination with climonorm in
      MPAH is the most cost-effective for public health care facilities and effective
      for patients. The course of MPAH is of certain peculiarity, which should be taken
      into account in choosing a therapeutic model for this category of patients.

PMID- 14664168
TI  - [Autonomic balance and some daily ECG monitoring parameters in patients with
      prior myocardial infarction].
AB  - The specific features of ischemic and arrhythmic manifestations and their
      relationship to the autonomic nervous system studied by analysis heart rhythm
      variability (CRV) were investigated in 87 patients with prior large myocardial
      infarction by using Holter monitoring. Spectral analysis of CRV revealed that in
      painful ischemia (PI) the total frequency (TF) of waves significantly decreased
      by 22%. In turn, episodes of silent ischemia (SI) were associated with a
      substantial (42%) increase in VLF-range power with a simultaneous significant
      reduction in the HF region of the spectrum by 53.8%. At the same time, the PI and
      SI groups greatly differed in the severity of complicated ventricular arrhythmias
      registered in 66.7 and 24.4% cases, respectively (p < 0.01). Thus, differences
      have been found in the episodes of myocardial ischemia: the pain equivalents are
      characterized by a higher risk for arrhythmia and SI is likely to be associated
      with the imbalance of ANS and with higher neurohumoral activity.

PMID- 14664169
TI  - [Biorthythmological risk factors for progression of coronary heart disease].
AB  - The study was undertaken to study a role of periods of an individual annual cycle
      (IAC) (from the date of a birthday to the following one) and the season of a year
      in patients with coronary heart disease (CHD) in its progression. The study
      enrolled 52 patients with functional classes II and stable angina pectoris.
      Clinical and functional parameters were estimated by the data of bicycle
      ergometric test (BET), 24-hour monitoring (24-h M), ECG, and echocardiography.
      The vast majority of cases of progression of angina were observed in autumn and
      winter. Moreover, in patients with angina, the duration of silent ischemia
      significantly increased and heart rate variability decreased in winter and that
      of painful ischemia increased in autumn, as evidenced by 24-h M. Trimesters 1
      (months 1 to 3 from the date of birth) and particularly IV (months 10 to 12 from
      the date of birth) have been found to be characterized by a poor course of CHD.
      Thus, in trimester IV, the duration of total, and silent ischemia significantly
      prolonged, as shown by 24-h M; episodes of latent coronary insufficiency
      increased in number, as evidenced by BET. Thus, the course of CHD is determined
      by a number of biorhythmological factors: the season of a year and the period of
      IAC.

PMID- 14664170
TI  - [The stomach and duodenum condition in patients with chronic obstructive lung
      diseases].
AB  - Examining the gastroduodenal mucosa (GDM) in 61 patients with chronic obstructive
      pulmonary diseases (COPD) showed changes in the areas studied in all cases. GDM
      atrophy increased with the severity of COPD. Helicobacter pylori are essential in
      developing gastric pathology in patients with mild bronchopulmonary disease. The
      severity of atrophic gastritis increases with the longer duration of COPD and
      with more severity of hypoxia and bronchial obstruction.

PMID- 14664172
TI  - [Manifestations of local fibrosis in the clinical picture of carcinoids of
      digestive organs].
AB  - A complex of clinical, functional, and morphological studies was made in 20
      patients aged 39 to 78 years who had histologically verified gastrointestinal
      carcinoids in the pre- and postoperative periods, by employing laboratory tests
      and instrumental techniques. Removed tumors were morphologically studied. Sixteen
      patients were operated on. Among them, 10 and 6 patients underwent planned and
      emergency operations, respectively. On referral for emergency laparotomy, the
      preoperative diagnoses were acute ileus in 2 cases, acute pancreatitis in 1, and
      acute appendicitis in 3. The local paracrine effect of serotonin on the
      intestinal wall leads to spasm and fibrosis, which manifests itself as the
      clinical picture of obstruction of a hollow organ or acute appendicitis. Cordlike
      or concentrated deformity as a kink is a characteristic sign of small intestinal
      carcinoid. Formation of fibrosis occurs not only in the pathways of evacuation of
      excess serotonin from hepatic metastases into the right ventricle of the heart
      (Hedinger's syndrome), but by the paracrine pathway in the immediate vicinity of
      a carcinoid tumor, in whatever organ the tumor is located.

PMID- 14664171
TI  - [Level of Helicobacter pylori infection of the gastric mucosa in the optimization
      of a daily dose of antihelicobacter drugs].
AB  - The efficiency of antihelicobacter therapy was evaluated in 36 and 22 patients
      from experimental and control groups, respectively. In the control group,
      antihelicobacter agents were given in usual doses in the control group and in the
      experimental one; they were used in doses depending on the level of Helicobacter
      pylori (HP) infection of the gastric mucosa (GM). The findings showed that the
      efficiency of antihelicobacter therapy was much higher in the group of patients
      taking antihelicobacter agents in a daily dose depending on the level of GM HP
      infection.

PMID- 14664173
TI  - [Synthesis of eicosanoids in the colonic mucosa in patients with ulcerative
      colitis].
AB  - The synthesis of cyclooxygenase (CO) and lipoxygenase (LO) metabolites of
      arachidonic acids, such as prostaglandins (PG) E2, F2 alpha, 6-keto-P1 alpha,
      thromboxane B2 (TB2), leukotriene B4 (LTB4) and hydroxyeicosatetraenic acids
      (HETEA) in the biopsy specimens of the colonic mucosa (CM) was studied in vitro
      in 30 patients aged 17-66 years who had ulcerative colitis (UC) of various
      severity and extent. The biopsy specimens of CM from 10 patients with the
      irritable bowel syndrome were used for comparison. A proportional severity of the
      disease and increased synthesis of CO and LO metabolites in CM was ascertained in
      a phase of UC. In the early phase of clinical remission (on the average,
      following 4 weeks of therapy), there was a comparative reduction in the level of
      eicosanoids with the preserved high production of TB2 and LO derivatives (LTB4
      and HETEA). At the same time, in patients with severe UC, a higher synthesis of
      LTB4 and HETEA and PG was preserved. The predominance of CM production of
      eicosanoids having aggregative, vasoconstrictor, and proinflammatory effects
      (less coefficients of 6-keto-PGF1 alpha/TB2 and PG/LTB4 + ETEA), which had been
      detected in a phase of UC exacerbation, was preserved in a phase of remission
      development, by forming the metabolic basis for recurrence of the process.

PMID- 14664174
TI  - [Clinical value of soluble adhesion molecules in systemic scleroderma].
AB  - The aim of the trial was to study clinical significance of estimation of cell
      adhesion soluble molecules (CASM) in scleroderma systematica (SS). Quantitation
      of CASM VCAM-1, ICAM-1 and R-selectin was made with enzyme-immunoassay (R&D
      System kits, USA) in 38 patients with SS (11 with limited SS and 27 with diffuse
      SS). The levels of VCAM-1, ICAM-1 and R-selectin was elevated in 30 (79%), 17
      (45%) and 20 (53%) patients, respectively. Mean values of VCAM-1 and ICAM-1 in
      patients were significantly higher than in healthy donors. R-selectin was also
      higher but insignificantly. A mean CASM level and a relative number of patients
      with elevated count of CASM in patients with diffuse and limited forms of SS did
      not differ. In 15 patients with active (progressive) course of the disease the
      level of VCAM-1 was significantly higher than in patients with chronic (non
      progressive) course of SS while concentrations of ICAM-1 and R-selectine were
      almost the same. Thus, SS patients have elevated levels of CASM. CASM VCAM-1
      concentration is the most sensitive marker of SS activity compared to other CASM.

PMID- 14664175
TI  - [Possibility of predicting the use of doxazosin in the treatment of arterial
      hypertension].
AB  - Fifteen patients with arterial hypertension (AH) were examined. Their peripheral
      venous hemodynamics, central circulation, systolic and diastolic functions were
      studied and a course therapy with doxazosin (cardura, Pfizer, USA) was performed
      for 30 days. Cardura (doxazosin) was found to be the drug of choice for
      antihypertensive therapy in patients with AH concurrent with baseline systemic
      venous normo- or hypertension. In patients with baseline venous hypervolemia in
      the presence of venous hypotension, cardura therapy resulted in deterioration of
      signs of venous insufficiency and promoted the development (in 38% of the cases)
      or progression (in 38%) of diastolic dysfunction of the left ventricle (LV).
      Thus, the venous circulation and LV myocardial function should be originally
      assessed in order to decide whether cardura (doxazosin) is used in
      antihypertensive therapy in patients with AH.

PMID- 14664176
TI  - [Diuress for the treatment of early stages of urolithiasis].
AB  - The efficacy of the plant diuretic Diuress is evaluated by using the rapid
      diagnosis program including renal ultrasonography, Lithos system, and urinary
      sediment microscopy.

PMID- 14664177
TI  - [Pulse-therapy with glucocorticoids and cyclophosphamide in the treatment of
      thromboangiitis obliterans].
AB  - Effectiveness of glucocorticoid and cyclophosphamide pulse-therapy was studied in
      patients with thrombangitis abliterans (TA). We examined 28 males. All of them
      were treated with antiplatelet agents and vasodilators in standard doses. In
      addition, 16 patients received a standard three-day scheme of a glucocorticoid
      and cyclophosphamide pulse-therapy. The examination of the patients was carried
      out before the treatment and in a month. Estimation of clinical activity was made
      according to the BVAS index, serum levels of C-reactive protein (CRP) and von
      Willebrand factor antigen (VWF-Ag), ESR. Before the start of the treatment there
      were no significant differences in the values of BVAS, ESR and CRP between the
      groups. In a month, BVAS index, concentrations, the rate of high serum levels of
      CRP and frequency of amputations were significantly reduced in patients treated
      with pulse-therapy. So, this pulse-therapy has a considerable anti-inflammatory
      effect and decreases frequency of amputations in thrombangiitis obliterans.

PMID- 14664178
TI  - [Neurological masks of hypothyroidism in adults: Pathogenesis, clinical picture,
      and diagnosis].
AB  - The lecture covers current concepts of the biochemical and pathophysiological
      mechanisms of nervous system lesions under hypothyroidism, presents a new
      classification and a detailed clinical picture of neurological manifestations of
      thyroid hypofunction. Some differential diagnostic aspects of neuromuscular,
      neuropsychic, and autonomic disorders in this pathology are given. Particular
      attention is given to the impact of myxedematous edema on the function of cranial
      nerves.

PMID- 14664179
TI  - [Documented case of recurrent herpes zoster].
AB  - The paper presents a comparative description of the clinical picture of herpes
      zoster observed in a patient twice in 1989 and 1997. For its differential
      diagnosis with herpes simplex, emphasis is laid on a difference between the
      concepts "relapse" and "recurrence".

PMID- 14664180
TI  - [A combination of non-Hodgkin lymphoma of the small bowel and primary sclerosing
      cholangitis with isolated lesion of small ducts].

PMID- 14664181
TI  - [Prospects and applications of the new techniques of localization with biopsy and
      radio-guided surgery].

PMID- 14664182
TI  - [Current status and prospects of laparoscopic surgery in rectal cancer].

PMID- 14664183
TI  - [Metachronous carcinoma of the colon: report of a clinical case].
AB  - The Authors deal with a rare case of 'meta-metachronous' carcinoma of the colon.
      A seventy years old man was admitted to ward after being diagnosed an
      adenocarcinoma of the transverse colon. The anamnestic data pointed out that the
      patient had already been operated twice for the colon carcinoma, which had been
      diagnosed in the left colon and in the cecum respectively seven and two years
      before. A colonoscopy performed sixteen months before did not show any lesion of
      the residual colon. It is likely that tiny lesions, which were still in the
      adenoma phase, were not diagnosed by the endoscopy; it is also possible that the
      adenoma-carcinoma sequence was extremely fast. On the basis of this experience
      the Authors recommend that patients with metachronus carcinoma undergo either
      frequent controls or a preventive subtotal colectomy.

PMID- 14664184
TI  - [Complete rectal prolapse in a patient with Hirschsprung disease: a clinical
      case].
AB  - The disease of Mya-Hirschsprung (HD) it's rare and congenital, usually diagnosed
      in child age, but that it can also remain unknown until the adult age. It's
      associated to genetic mutations and it can involve other pathologies and
      malformations. The variability of the anatomopathological and clinical phenomena
      is correlated to the length of the aganglionic segment. The Authors describe the
      clinical case of one young female patient, who presented chronic constipation
      (less than 3 evacuations to week), tenesm, meteorism, abdominal pain. To the
      inspection of the anal region after the evacuation the presence of complete
      rectal prolapse (3) cylinders of the length of 30 cm was appraised, with presence
      of ulcerations of the mucosa. The patient came subordinate to diagnostic study
      that they demonstrated the presence of HD. The Authors operated the patient with
      the technique of Frykman and Goldberg. In the follow-up the patient had the
      complete remission of the symptomatology and resumption of the rectoanal
      inhibitory reflex, remarkable diminished in the preoperative manometric
      examination. The pathogenesis of the association of HD and rectal prolapse goes
      searched in the presence of ultrashort HD (aganglionic defect of a limited
      segment of rectum), pathological variety somewhat rare that can determine
      subocclusive phenomena and that it favors the prolapse of the rectum for the
      continuous evacuating strains.

PMID- 14664185
TI  - [A case of colonic multiple lipoma].
AB  - The Authors, after a review of the literature, report a case of multiple lipomas
      of the left colon. They analyse the diagnostic, pathogenetic and therapeutic
      features of this rare pathology.

PMID- 14664186
TI  - [Biliary ileum and surgical emergency].
AB  - The Authors report a case of intestinal occlusion due to a gallstone migrated in
      jejunum and, with a review of the literature, stress the difficult decision
      making for surgical timing in a critical patient.

PMID- 14664187
TI  - Factors affecting prognosis in patients with short bowel syndrome.
AB  - Aim of the study is to analyse physiopathological implications of massive
      intestinal resection and factors affecting prognosis in patients with short bowel
      syndrome. Twenty massive intestinal resections were performed. The causes of
      bowel resection were: intestinal infarction (11 cases), Crohn's disease (5
      cases), small bowel volvulus (4 cases). All intestinal resections were more than
      50-60% of the intestinal length. In eighteen patients intestinal anastomosis was
      performed immediately. In all the patients postoperative therapy with parenteral
      nutrition (PN) was performed. The operative morbidity and thirty-day mortality
      were respectively 30% (6 cases) and 35% (7 cases). The diarrhea was the dominant
      symptom. The average weight was 20% lower compared to the initial weight. The
      length of residual small bowel and type of anastomosis strongly affect survival
      of patients underwent massive intestinal resections. Parenteral nutrition (PN)
      has great importance in postoperative treatment. A useful treatment, in severe
      short bowel syndrome, can be small bowel transplantation.

PMID- 14664188
TI  - [Retroperitoneal liposarcoma].
AB  - Liposarcoma is the most frequent histotype of the rare and malignant
      retroperitoneal tumours. This neoplasm has a remarkable tendency to recurrence
      after surgical excision, rarely to metastasize. Recurrence usually shows a more
      aggressive behaviour than primitive disease with a higher tendency to penetrate
      into adjacent organs. The symptomatology often appears late and the first sign is
      frequently a palpable abdominal mass. Preoperative study involves using CT and
      MRI. The surgical resection is the only tool able to modify natural history with
      regard to survival and local recurrence. Prognosis is severe, with a survival of
      5 years, variable from 12 to 50% in the different series. A very important
      prognostic factor is the degree of tumour and radical surgical treatment. From
      1990 to 2001, 32 operations for malignant retroperitoneal tumors were performed
      by our surgical unit in 19 patients; in 7 of them the tumor was a liposarcoma (4
      male and 3 female). Total operations for retroperitoneal liposarcoma were 15, in
      4 patients a second operation was performed for recurrence, in 3 a third
      operation and in 1 a fourth. Eleven cases out of 15 have undergone exeresis of
      sarcoma. Average survival consisted in 4 years and 2 months. Intraoperative
      radiotherapy, performed in 3 patients, perhaps is able to offer some advantages
      in relation to local control of the disease and of the survival. A possible
      resection of eventual recurrence justifies a early follow up with CT and MRI.

PMID- 14664189
TI  - Splenic trauma following colonoscopy.
AB  - A case of splenic trauma after colonoscopy is reported. After description of
      their experience, the Authors report a review of the literature and some
      considerations about clinical diagnosis and surgical or medical therapy for this
      pathology.

PMID- 14664190
TI  - [Study of fecal antigens against Helicobacter pylori as non-invasive test
      compared with the 13C-urea breath-test. Personal experience].
AB  - The target of this study is the evaluation of two different noninvasive tests:
      13C-urea Breath-Test, as gold standard, versus the HpSA test, as new method to
      research the faecal antigen of Helicobacter Pylori (HP). Thirty patients,
      affected by dyspeptic symptomatology and never treated before by antibiotic
      therapy to eradicate the HP, was subjected, by Authors, to this evaluation. This
      study say that the 13C-urea Breath-test represent the gold standard in the pre
      endoscopic research of HP presence concerning specificity and sensibility.
      However, the HpSA test need more improvement.

PMID- 14664191
TI  - [Packing: current concepts of "life-saving" surgery].
AB  - Abdominal packing is a lifesaving technique for temporary control of severe
      injury and it is used in Damage Control Surgery schedule. Technically bleeding
      from abdominal cavity can generally be achieved by applying pressure with several
      large abdominal packs. It's possible too applying packs in organ-specific
      techniques (early abdominal packing). A wide review of the literature has allowed
      to emphasize the most common problem of this technique, the adequacy of the
      particular indications, their evolution, timing, the results in general and
      particular which multiple critical situations and not always predictable when an
      intensive diagnostic and methodological approach is necessary in. The principal
      indications are when complex anatomic lesions are diagnosed with not ruleable
      hemorrhages, in presence of metabolic failure--like hypothermia < 35 degrees C,
      acidosis > 7.2, coagulopathy PTT > 16 seconds: these three derangements become
      established quickly in the exsanguinating trauma patient and, once established,
      form a vicious circle which may be impossible to overcome. The results are
      encouraging and we can evaluate a median survival of the 60%, certainly superior
      to the obtainable survival with immediate surgical repair. Immediate failures are
      substantially due to bleeding, especially in "underpacking" case, and remote:
      these last can be premises, fundamentally septic and bound at the time of stay
      (above the 72 hours) and associated by the coexistence of lesions; in these
      situations is possible a MOF syndrome due to excessive intraabdominal pressure
      (overpacking) or to an abdominal compartment syndrome.

PMID- 14664192
TI  - Support networks used by African American breast cancer support group
      participants.
AB  - Informal and formal support networks are used by women to cope with the physical
      and psychological consequences of breast cancer. This study explored the support
      networks used by 43 southeastern United States African American women who
      participated in African American breast cancer support groups. Both qualitative
      and quantitative approaches were used. African American women were found to rely
      more on God for support than either family or friends. Health care professionals
      and Internet use was reported less often as a source of support among these
      women. We conclude that support group use does not decrease African American
      women's strong reliance on God as a source of support.

PMID- 14664193
TI  - Elderly African American women's knowledge and belief about colorectal cancer.
AB  - The purpose of this pilot study using focus groups was to 1) identify elderly
      African American women's knowledge and belief about colorectal cancer, 2)
      determine whether African American elderly women seek preventative measures for
      colorectal cancer, and 3) determine the educational needs to increase
      participation in colon cancer screening. The author used a convenience sample of
      15 African-American women between the ages of 45-69 recruited from a moderately
      large church in a major urban city. Results of the study showed that there was a
      very low level of participation in colon cancer screening among the women in the
      group. Over 70 percent had a college degree or higher and 62 percent had no
      knowledge about colorectal cancer. 77 percent were employed with 69 percent
      having health insurance; 38 percent did not perceive themselves at any risk for
      colorectal cancer; and only 23 percent stated that they had been tested for colon
      cancer. Reasons for not getting screened were: fear; afraid of pain; doctor never
      recommended any tests; had no symptoms; competing health histories;
      embarrassment; and flaws in risk perception.

PMID- 14664194
TI  - A nurse speaks out ... preventable back injuries and nursing.

PMID- 14664195
TI  - The complete blood cell count: a powerful diagnostic tool.
AB  - In conclusion, the CBC can be a powerful diagnostic tool. Appropriate evaluation
      of all aspects of the CBC can lead to a specific diagnosis or assist in ruling
      out many diseases. To gain the full benefit of the CBC, it must be used in
      conjunction with a good history and physical examination as well as with
      additional components of the minimum database, which include a chemistry panel
      and urinalysis.

PMID- 14664196
TI  - Clinical application of reticulocyte counts in dogs and cats.
AB  - Reticulocytes are anucleate immature red blood cells that contain a network of
      RNA, organelles, and mitochondria, which stain with supravital dyes. Both
      aggregate and punctate reticulocytes are present in domestic cats, and aggregate
      reticulocytes are used to assess the degree of regeneration in anemic dogs and
      cats. Multiple factors influence the degree of regenerative response to anemia.
      These factors include time of reticulocyte measurement, concurrent diseases,
      species, and ongoing therapy. Although many automated systems for reticulocyte
      enumeration exist, manual counts remain the gold standard in veterinary medicine.

PMID- 14664197
TI  - The use of erythropoietin.
AB  - EPO is a hematopoietic growth factor produced in the kidney that stimulates
      erythropoiesis. It effectively treats hypoproliferative anemia associated with
      CRF, improving quality of life in these patients. Other uses that are poorly
      characterized in veterinary medicine include treatment of cancer patients on
      chemotherapy, hematologic disorders, and anemic FeLV-infected cats as well as
      preoperative conditioning for elective surgeries that may involve significant
      blood loss. Careful monitoring of therapy is necessary for optimal results.
      Several complications are associated with rHuEPO therapy. The production of anti
      rHuEPO antibodies is the most significant and can be a life-threatening event.
      Alternatives to human EPO are being sought to provide beneficial effects while
      avoiding antibody formation.

PMID- 14664198
TI  - Triggers for use, optimal dosing, and problems associated with red cell
      transfusions.
AB  - The administration of RBC components can dramatically improve tissue oxygenation
      in small animals with symptomatic anemia and can be life saving. This therapy is
      not without risk, however. Careful consideration of the transfusion trigger,
      appropriate screening of the donor and recipient, and selection of the optimal
      RBC component and dose on an individual patient basis can help to limit the
      occurrence of adverse transfusion-related events. Appropriate component
      administration techniques, careful monitoring of recipients for the development
      of transfusion reactions, and prompt recognition and treatment of transfusion
      reactions are also essential in assuring safe transfusion practice.

PMID- 14664199
TI  - Clinical application of a hemoglobin-based oxygen-carrying solution.
AB  - Oxyglobin, a hemoglobin-based oxygen-carrying fluid, is indicated in the
      treatment of anemia in dogs and may be life saving if compatible red blood cells
      are not available for transfusion. The colloidal properties of Oxyglobin allow
      for expansion of the circulatory volume, which may be helpful in patients with
      hypovolemia, especially hemorrhagic shock. Oxyglobin's colloidal properties can
      also lead to circulatory overload, with development of pulmonary edema and
      pleural effusion, however, necessitating careful monitoring of the rate of
      administration and of the respiratory rate and effort of the patient. Measurement
      of total or plasma hemoglobin concentration can be used as an aid in monitoring
      patients receiving Oxyglobin.

PMID- 14664200
TI  - Immune-mediated hemolytic anemia: understanding the nemesis.
AB  - IMHA is one of the most common causes of anemia in small animals. Although
      treatment may be rewarding, many patients do not respond adequately to
      glucocorticoids alone and require additional immunosuppressive therapy. Some
      patients may succumb to acute severe anemia and die within the first few weeks of
      treatment; even if they survive, relapses may occur. IMHA is the nemesis; as our
      understanding of this disease increases and treatment options expand, it is hoped
      that survival rates will finally improve.

PMID- 14664201
TI  - New insights into the physiology and treatment of acquired myelodysplastic
      syndromes and aplastic pancytopenia.
AB  - MDS are a diverse group of primary and secondary bone marrow disorders that are
      characterized by cytopenias in blood, prominent dysplastic features in blood or
      bone marrow, and normal or hypercellular bone marrow. MDS in cats are typically
      associated with FeLV infection. Dogs with MDS-RC and MDS-Er seem to respond to
      erythropoietin administration and have prolonged survival. Dogs with MDS-EB
      respond poorly to present treatments, and survival is short. Prognosis and
      probability of progression to acute myelogenous leukemia can be predicted based
      on the percentage of myeloblasts in bone marrow. Several experimental therapeutic
      modalities in human beings have been described that may be useful in treating MDS
      EB in dogs and cats. Aplastic pancytopenia is a relatively rare disorder in dogs
      and cats. Causes include Ehrlichia spp, Parvovirus, and FeLV infections; sepsis;
      chronic renal failure; drug and toxin exposure; and idiopathic causes. Diagnosis
      is based on identification of multiple cytopenias in the blood and
      hypoplastic/aplastic bone marrow, with the marrow space replaced by adipose
      tissue. Treatment and outcome are dependent on determining the underlying cause
      of the bone marrow failure.

PMID- 14664203
TI  - Investigation of hypereosinophilia and potential treatments.
AB  - Hypereosinophilia is excessive eosinophilia and has been defined in dogs and cats
      as eosinophils greater than 5 x 10(9)/L (> 5000/microL). Canine breeds with a
      predisposition to higher eosinophil counts or certain eosinophilic diseases
      include the Rottweiler, German Shepard, Siberian Husky, Alaskan Malamute, and
      Cavalier King Charles Spaniel. Two of the more common causes of canine
      hypereosinophilia are pulmonary infiltrates with eosinophils (PIE) and
      gastrointestinal disease. The highest eosinophil counts are expected in dogs with
      pneumonia or PIE. The most common cause of eosinophilia in cats is flea allergy.
      The greatest eosinophilia occurs in cats with flea allergy, feline asthma, and
      eosinophilic granuloma. Innovative recent treatments for human patients with
      asthma have been successful in reducing eosinophil numbers but have had a
      confusing and disappointing lack of reducing symptoms. The role of eosinophils in
      many eosinophilic diseases remains a mystery.

PMID- 14664202
TI  - Clinical assessment of leukocytosis: distinguishing leukocytoses caused by
      inflammatory, glucocorticoid, physiologic, and leukemic disorders or conditions.
AB  - The four major types of leukocytoses are inflammatory, glucocorticoid-associated,
      catecholamine-associated, and neoplastic. These leukocytoses are distinguished by
      leukocyte concentrations, microscopic features of leukocytes, and associations
      with other laboratory data. All laboratory findings need to be interpreted within
      the context of the case information, including signalment, history, and physical
      examination findings. Newer assays are being used to differentiate the different
      forms of leukocyte neoplasia and to distinguish between hyperplastic and
      neoplastic proliferations.

PMID- 14664204
TI  - Chronic lymphocytic leukemia in dogs and cats: the veterinary perspective.
AB  - Chronic lymphocytic leukemia (CLL) in dogs and cats shares many similarities with
      its human counterpart but also has significant differences. In marked contrast to
      people, CLL in dogs and cats is primarily a T-lymphocyte proliferation. Cytotoxic
      T-cell proliferations with granular lymphocyte morphology predominate in dogs,
      and T helper cell proliferations seem to be most common in cats with CLL.
      Immunophenotyping and assessment of clonality by molecular genetic analysis are
      newer adjunctive tools in veterinary medicine that are useful in the
      characterization and diagnosis of CLL in dogs and cats. The clinical
      presentation, typical hematologic findings, diagnosis, course of disease,
      prognosis, and therapy of CLL in dogs and cats are discussed.

PMID- 14664205
TI  - Triggers for prophylactic use of platelet transfusions and optimal platelet
      dosing in thrombocytopenic dogs and cats.
AB  - Prophylactic platelet transfusions are frequently given to human patients with
      hypoproliferative thrombocytopenia. For several decades, the most common
      transfusion trigger was 20,000/microL, but the trend is now to use 10,000/microL
      in the absence of other risk factors for bleeding. This trigger seems to reduce
      the number of transfusions without increasing the risk of severe bleeding. Most
      studies involved in establishing platelet transfusion policies have involved
      patients with acute leukemia, with fewer studies involving patients undergoing
      hematopoietic stem cell transplantation or aggressive chemotherapy for other
      cancers and patients with aplastic anemia. In the presence of other risk factors
      for spontaneous bleeding, 20,000/microL is still considered an appropriate
      trigger. The trigger for prophylactic transfusion before surgery has not
      undergone the same recent scrutiny as has the trigger for spontaneous bleeding.
      The recommendation remains to raise the platelet count to 50,000 to
      100,000/microL if possible, although it is recognized that surgery and other
      invasive procedures have been performed at lower platelet counts without major
      bleeding. Prophylactic transfusion is not used in disorders of platelet
      consumption and destruction to prevent spontaneous bleeding but is used before
      surgery. Because of the comparative lack of experience with platelet transfusion
      in veterinary medicine, it is difficult to make generalizations for dogs and
      cats. Using the guidelines established for therapeutic and prophylactic
      transfusion of human patients is a reasonable starting point, however. A
      therapeutic transfusion policy is suggested in the veterinary setting provided
      that the patient can be closely observed for critical bleeding and a prompt
      transfusion can be given. This policy should ultimately reduce the overall number
      of platelet transfusions given to hospital patients. If an animal cannot be
      closely observed or the ability to transfuse on demand is limited, prophylactic
      transfusion is recommended. The triggers for initiating a platelet transfusion in
      dogs are extrapolated from human data; these values are lower by 50% for cats.
      Because of the imprecision of platelet counting at low values, platelet counts
      must always be interpreted in conjunction with clinical signs of hemorrhage. If
      platelet-rich plasma or platelet concentrate is available, a dose of 1 platelet
      unit per 10 kg is recommended, although resources may dictate a smaller dose.
      This will raise the recipient platelet count by a maximum of about 40,000/microL.
      Assuming a trigger of 10,000/microL, a transfusion will probably be required
      approximately every 3 days. It must be remembered that the frequency of platelet
      transfusions may be greater in the presence of factors accelerating platelet loss
      or destruction. If fresh whole blood is used, a rule of thumb is to transfuse 10
      mL/kg, which will raise the recipient platelet count by a maximum of
      approximately 10,000/microL. Daily transfusions or transfusions every other day
      will probably be required.

PMID- 14664206
TI  - Plasma D-dimer for the diagnosis of thromboembolic disorders in dogs.
AB  - D-dimer is formed during thrombus formation when factor XIIIa crosslinks the
      terminal D-domains of fibrin. The D-dimer epitope is exposed when the thrombus is
      lysed by plasmin. Thus, D-dimer represents both thrombin and plasmin activation
      and is specific for fibrinolysis. D-dimer concentrations are increased in dogs
      with DIC or other thromboembolic disorders, but because D-dimer is an indicator
      of physiologic or pathologic fibrinolysis, values are elevated in other
      conditions associated with fibrinolysis, including orthopedic surgery, neoplasia,
      and internal hemorrhage. It can be used as an ancillary test for the diagnosis of
      DIC but is not recommended as a sole test for this purpose. D-dimer has the
      potential to be a useful laboratory test for the detection of pulmonary
      thromboembolism in dogs. Further studies are needed to determine the appropriate
      applications for this test in veterinary patients to aid in clinical decision
      making, treatment, and patient care.

PMID- 14664207
TI  - Potential uses of recombinant human factor VIIa in veterinary medicine.
AB  - In human beings, rFVIIa has been used successfully to promote hemostasis in
      patients with various bleeding disorders. Patients with hemophilia,
      thrombocytopenia, and thrombocytopathy have been effectively and safely treated
      as well as patients with severe trauma or surgery resulting in profuse bleeding
      and patients with impaired liver function. Given these successes, the possibility
      of using rFVIIa in veterinary medicine is appealing. The clinical indications and
      uses in veterinary medicine would be similar, but there are currently two major
      obstacles: immunogenicity and cost. If these problems can be addressed, rFVIIa
      may become a valuable and indispensable therapy, especially in the emergency and
      critical care settings. The use of rFVIIa could allow for successful treatment of
      otherwise intractable bleeding as well as decrease the number of blood
      transfusions needed.

PMID- 14664209
TI  - They're back!

PMID- 14664208
TI  - New perspectives about Hemotrophic mycoplasma (formerly, Haemobartonella and
      Eperythrozoon species) infections in dogs and cats.
AB  - The new perspectives about hemotrophic mycoplasma infections in cats and dogs can
      be summarized as follows: Haemobartonella and Eperythrozoon species infecting the
      dog and cat have been reclassified as mycoplasmal parasites and given the names M
      haemofelis (Ohio or large form of H felis), M haemominutum (California or small
      form of H felis), and M haemocanis (H canis). The prevalence of hemotrophic
      mycoplasma infections in anemic cats in the United States is about 25% and
      usually involves M haemofelis. However, nonanemic cats may also be infected most
      commonly with M haemominutum. Chronic infections with hemotrophic mycoplasmas may
      promote myeloproliferative disorders in FeLV-infected cats. M haemocanis
      infection in dogs may be a widespread latent disease in kennel-raised dogs and is
      being investigated. The PCR assay is exquisitely sensitive for detection of M
      haemofelis and M haemominutum, and testing of blood donor cats and perhaps dogs
      should be done regularly. Fleas are involved in the transmission of M haemofelis
      to the cat, whereas R sanguines may be involved with transmission of M haemocanis
      to the dog. Treatment with doxycycline effectively controls acute infection in
      the cat and dog, and enrofloxacin may also be effective in the cat, but none of
      the antibiotics tested to date consistently clears the parasites.

PMID- 14664210
TI  - Liquor on the breath!

PMID- 14664211
TI  - Treating the patient with Parkinson's disease.

PMID- 14664212
TI  - Ending the dentist-patient relationship.

PMID- 14664213
TI  - Section 125 plans save money for you and your employees.

PMID- 14664214
TI  - ADA board focuses on dental education.

PMID- 14664215
TI  - Why dentistry is important to us. "Oral health care is primary care".

PMID- 14664216
TI  - Why dentistry is important to us. We need oral health for all Michigan residents.

PMID- 14664217
TI  - "Your kid is a brat and she's driving me crazy!".

PMID- 14664218
TI  - Practice transitions: how to unlock your practice's hidden value.

PMID- 14664219
TI  - Your voice: a neglected marketing tool.

PMID- 14664220
TI  - Estimates of HIV prevalence and incidence in Canada, 2002.

PMID- 14664221
TI  - Nitrification in a zeoponic substrate.
AB  - Clinoptilolite is a zeolite mineral with high cation exchange capacity used in
      zeoponic substrates that have been proposed as a solid medium for growing plants
      or as a fertilizer material. The kinetics of nitrification has not been measured
      for NH4+ saturated zeoponic substrate. Experiments were conducted to evaluate the
      production of NO2- and NO3-, and nitrifier populations in zeoponic substrates.
      Small columns were filled with zeoponic substrate inoculated with a commercial
      inoculum or soil enrichment culture of nitrifying bacteria. In addition to column
      studies, a growth chamber study was conducted to evaluate the kinetics of
      nitrification in zeoponic substrates used to grow radishes (Raphanus sativus L.).
      The zeoponic substrate provided a readily available source of NH4+, and
      nitrifying bacteria were active in the substrate. Ammonium oxidation rates in
      column studies ranged from 5 to 10 micrograms N g-1 substrate h-1, and NO2-
      oxidation rates were 2 to 9.5 micrograms N g-1 substrate h-1. Rates determined
      from the growth chamber study were approximately 1.2 micrograms N g-1 substrate h
      1. Quantities of NH4+ oxidized to NO2- and NO3- in inoculated zeoponic substrate
      were in excess of plant up-take. Acidification as a result of NH4+ oxidation
      resulted in a pH decline, and the zeoponic substrate showed limited buffering
      capacity.

PMID- 14664223
TI  - [Annex I. Articles of the association: European Federation of Hand Emergency
      Services].

PMID- 14664222
TI  - [Value in heart failure proven again. AT II blocker soon also for post-infarct
      patients?].

PMID- 14664225
TI  - Light extinction and absorption by arbitrarily oriented finite circular cylinders
      by use of geometrical path statistics of rays.
AB  - From the geometrical path statistics of rays in an anomalous-diffraction theory
      (ADT) [Opt. Lett. 28, 179 (2003)] closed-form expressions for the geometrical
      path distribution of rays and analytical formulas for the optical efficiencies of
      finite circular cylinders oriented in an arbitrary direction with respect to the
      incident light are derived. The characteristics of the shapes of the cylinders
      produce unique features in the geometrical path distributions of the cylinders
      compared with spheroids. Gaussian ray approximations, which depend only on the
      mean and the mean-squared geometrical paths of rays, of the optical efficiencies
      of finite circular cylinders and spheroids are compared with the exact optical
      efficiencies in ADT. The influence of the difference in shape between cylinders
      and spheroids on the optical efficiencies in ADT is illustrated by their
      respective geometrical path distributions of rays.

PMID- 14664224
TI  - [Editorial].

PMID- 14664226
TI  - Self-assembling and membrane modifying properties of a lipopeptaibol studied by
      CW-ESR and PELDOR spectroscopies.
AB  - Trichogin GA IV is a short lipopeptaibol antibiotic that is capable of enhancing
      the transport of small cations through the phospholipid double layer of the
      membrane. The antibiotic activity of the undecapeptide is thought to be based on
      either its self-assembling or membrane-modifying property. The chemical
      equilibrium between self-aggregated and non-aggregated molecular states was
      studied by CW-ESR spectroscopy using solutions of TOAC nitroxide spin-labelled
      trichogin analogues in an apolar solvent to mimic the membrane bound state. At
      room temperature the two different sets of signals observed in the spectrum were
      attributed to the presence of both monomers and aggregates in the sample. The ESR
      spectra of the monomeric and aggregated forms were separated and the dependence
      of the fraction of monomeric peptide molecules on concentration was obtained over
      the range 5 x 10(-6) to 7 x 10(-4) M. A two-step aggregation mechanism is
      proposed: dimerization of peptide molecules followed by aggregation of dimers to
      assemblies of four peptide molecules per aggregate. The equilibrium constants
      were estimated for both steps. In addition, the lower lifetime limit was
      determined for dimers and tetramers. It is shown that when the peptide
      concentration exceeds 10(-5) M. the major part of the peptide molecules in
      solution has the form of tetrameric aggregates. Independently, the PELDOR
      technique was used to investigate the concentration dependence of the parameters
      of the dipole-dipole interaction between spin labels in frozen (77 K] glassy
      solutions of aggregates of mono-labelled TOAC analogues. The number of molecules
      in aggregates as well as the frequency and amplitude of PELDOR signal
      oscillations were found to be concentration independent in the range 5 x 10(-4)
      to 8 x 10(-3) M. In the frozen glassy solution state, the number of peptide
      molecules per aggregate was determined to be close to four, which is in agreement
      with the value obtained for spin-labelled trichogin at room temperature. The
      present data provide experimental evidence in favour of a self-assembling rather
      than a membrane-modifying ion conduction mechanism.

PMID- 14664227
TI  - Ethics code and neuropsychological assessment practices.
AB  - The 1992 revision of the Ethics Code of the American Psychological Association is
      more detailed than its predecessor. Sections with direct relevance to
      neuropsychological assessment practice are discussed. Commentary and specific
      recommendations are provided regarding the issues of avoiding harm to patients,
      competence of the practitioner, test validity, test interpretation, maintenance
      of records, use and supervision of nondoctoral personnel, forensic activities,
      release of raw data, documentation of results, multiple relationships, and fees.
      Clinicians are urged to adhere to the Ethics Code rather than to a personnel
      standard of professional behavior.

PMID- 14664228
TI  - Perindopril (Coversyl) prevents cardiovascular death and MI in coronary disease
      patients regardless of their cardiovascular risk.

PMID- 14664230
TI  - Current awareness on yeast.

PMID- 14664229
TI  - Cipla Medpro addresses the link between homocysteine and cardiovascular risk.

PMID- 14664231
TI  - CHARM shows benefits of Atacand for symptomatic heart failure.

PMID- 14664232
TI  - Evidence for use of low molecular weight heparin (Clexane) in STEMI.

PMID- 14664233
TI  - ACTION results of nifedipine in stable angina due next year.

PMID- 14664234
TI  - Rosuvastatin receives FDA approval.

PMID- 14664235
TI  - Unsurpassed glycaemic control made simple.

PMID- 14664236
TI  - Discussion. Section 1: nonsteroidal antiinflammaory agents.

PMID- 14664238
TI  - Discussion. Section 3: gene therapy.

PMID- 14664237
TI  - Discussion. Section 2: immunomodulatory intervention.

PMID- 14664239
TI  - Discussion. Section 4: cartilage destruction and protection.

PMID- 14664240
TI  - ADDLs: a new explanation for Alzheimer disease?

PMID- 14664241
TI  - Crunching the bio-numbers.

PMID- 14664242
TI  - Sequencing CYP: more data allows cross-species comparison.

PMID- 14664243
TI  - Medical image. Chronic obstructive pulmonary disease: the spectrum of smoking
      related lung disease.

PMID- 14664245
TI  - Consensus statement from the German Sleep Society: indications for performing
      polysomnography in the diagnosis and treatment of restless leg syndrome.

PMID- 14664244
TI  - Skin protectant drug products for over-the-counter human use; final monograph;
      technical amendment. Final rule; technical amendment.
AB  - The Food and Drug Administration (FDA) is amending the regulation that
      established conditions under which over-the-counter (OTC) skin protectant drug
      products are generally recognized as safe and effective and not misbranded as
      part of FDA's ongoing review of OTC drug products. This amendment revises several
      of the indications for OTC skin protectant drug products to provide additional
      labeling claims that should not have been excluded from the final monograph (FM).

PMID- 14664246
TI  - Mother-to-child HIV transmission in India.

PMID- 14664247
TI  - Polio eradication plans face opposition.

PMID- 14664248
TI  - Clinton pledges cheap antiretrovirals.

PMID- 14664249
TI  - Progress on the treatment of hepatitis C.

PMID- 14664250
TI  - Gates Foundation takes "reality-driven" vision to the field.

PMID- 14664251
TI  - The abundance of alpha-tubulin mRNA increases during ciliary regeneration in
      Tetrahymena, and this occurs independently of the soluble tubulin content.
AB  - Control mechanisms of tubulin synthesis are analyzed during ciliary regeneration
      of the ciliate Tetrahymena. Titration of the alpha-tubulin mRNA concentrations
      during the regeneration period reveal that enhancement of tubulin synthesis is
      preceded and accompanied by increased concentrations of tubulin mRNA molecules.
      Stimulation of tubulin synthesis is independent of the pool size of soluble
      tubulin molecules, as suggested by at least two independent lines of evidence:
      First, like cells of normal phenotype a temperature sensitive size mutant
      enhances tubulin synthesis as well as tubulin mRNA concentration during ciliary
      regeneration, although these large mutant cells have a much higher concentration
      and amount of soluble tubulin molecules in the cytoplasm. Second, slowly
      regenerating cells of normal phenotype shift-up their concentration of tubulin
      mRNA molecules already before a time, when ciliary outgrowth might cause a
      significant depletion of the pool of soluble tubulin molecules. Thus, neither an
      induction of tubulin synthesis nor an increase in tubulin mRNA molecules is
      mediated via changes in the pool size of soluble tubulin molecules.

PMID- 14664252
TI  - In the interest of ethics.

PMID- 14664254
TI  - Giving back: are you doing your part?

PMID- 14664255
TI  - Evidence-based dentistry.

PMID- 14664256
TI  - Dental education.

PMID- 14664257
TI  - Balancing business with professionalism.

PMID- 14664258
TI  - Lesions and abfractions.

PMID- 14664259
TI  - More about noncarious lesions.

PMID- 14664260
TI  - Third dental therapeutics guide debuts at ADA session.

PMID- 14664261
TI  - Digital disaster: a cautionary tale.

PMID- 14664262
TI  - The implant-supported overdenture as an alternative to the complete mandibular
      denture.
AB  - BACKGROUND: Approximately one-third of Americans older than 65 years of age are
      fully edentulous, requiring replacement of missing teeth. While the conventional
      denture may meet the needs of many patients, others require more retention,
      stability, function and esthetics, especially in the mandible. The implant
      supported prosthesis is an alternative to the conventional removable denture.
      METHODS: This article describes the strengths of the implant-supported mandibular
      overdenture. The authors also outline the risks of this approach. They performed
      a review of recent literature to summarize the reported success rate of implants
      used to support a mandibular overdenture. RESULTS: The literature review
      indicates that implants placed in the anterior mandible (anterior to the foramen)
      have a success rate better than 95 percent. Patients have reported a high degree
      of satisfaction with the implant-supported overdenture. CONCLUSIONS: The
      literature indicates that implant-supported overdentures in the mandible provide
      predictable results with improved stability, retention, function and patient
      satisfaction compared with conventional dentures. Implants placed in the anterior
      mandible have a success rate equal to or greater than 95 percent. CLINICAL
      IMPLICATIONS: When planning treatment for patients with edentulous mandibles,
      clinicians should consider the implant-supported prosthesis.

PMID- 14664263
TI  - Surgical uprighting and repositioning of severely impacted mandibular second
      molars.
AB  - BACKGROUND: Impacted second molars can create problems with esthetics,
      masticatory function and dental arch stability. Treatment options include
      surgical extraction, surgical uncovering with orthodontic-assisted eruption and
      surgical uprighting. CASE DESCRIPTION: The authors review the literature
      concerning surgical molar uprighting, and present a case in which the procedure
      was performed successfully to treat an impacted second molar in a female
      adolescent. The authors surgically repositioned a horizontal, right mandibular
      second molar that was partially impacted in bone. The patient was followed up for
      three years, during which time she was free of complications. CLINICAL
      IMPLICATIONS: Surgical molar uprighting has been shown to be a predictable and
      reliable procedure. When a molar tooth is severely impacted, surgical uprighting
      provides a viable option when other treatment modalities are contraindicated.

PMID- 14664264
TI  - Galvanic interaction between gold and amalgam: effect of zinc, time and surface
      treatments.
AB  - BACKGROUND: Previous studies have investigated the electrolytic action of oral
      electrogalvanism. However, the reasons why certain treatments or materials are
      successful in reducing galvanic current have not been addressed fully. This study
      assessed galvanic current with several materials, surface conditions and
      treatments. METHODS: The authors measured galvanic currents between a type 3 cast
      gold alloy and Dispersalloy Dispersed Phase Alloy (zinc) (Dentsply Caulk,
      Milford, Del.) under different surface conditions using a zero-resistance-ammeter
      technique in a synthetic saliva solution for 10 hours. In addition, the galvanic
      currents between the same gold and Tytin alloy (non-zinc) (Kerr, Orange, Calif.),
      experimental zinc alloy (same makeup as that of Tytin, with the addition of zinc)
      and non-zinc dispersed-phase experimental alloy (essentially the same physical
      and chemical makeup as that of Dispersalloy, with the exclusion of zinc) were
      measured. Triplicate tests were performed for each condition. RESULTS: The
      statistical analysis indicated that electrogalvanic activity is reduced
      significantly when the amalgam surface is treated with tin oxide or silver
      nitrate. Both zinc-containing amalgams in their as-carved condition exhibited
      higher anodic charge densities than did their zinc-free counterparts. Galvanic
      current measured in Dispersalloy was reduced with the passage of time after
      carving. CONCLUSION: Galvanic interaction between cast gold and amalgam is
      reduced with time and surface treatments, but is increased considerably when the
      amalgam contains zinc. CLINICAL IMPLICATIONS: Amalgam restorations containing
      zinc that are in contact with gold restorations occasionally elicit galvanic
      pain. Selection of a non-zinc-containing amalgam will reduce the level of
      galvanic interaction. Galvanic pain from occlusal contact is reduced or
      eliminated when the restoration is brushed with tin oxide immediately after
      carving or is treated with 2 percent silver nitrate. Some patients may benefit
      from having their teeth separated with nonconducting rubber dam material.

PMID- 14664265
TI  - Comparison of direct digital and conventional intraoral radiographs in detecting
      alveolar bone loss.
AB  - BACKGROUND: Intraoral radiographs are important diagnostic aids in periodontics.
      The authors conducted a study to compare estimates of bone levels from direct
      digital and conventional radiographic under normal clinical use. METHODS: A full
      mouth series of conventional radiographs was taken for each of 25 subjects who
      had periodontitis. A long cone paralleling technique was used for periapical, or
      PA, images, and a paper sleeve with biting tab was employed for bitewing, or BW,
      images. A set of direct digital radiographs matching the conventional radiographs
      was taken for each subject under the same conditions. The distance from the
      cementoenamel junction to the interproximal alveolar crest on all readable
      surfaces was measured. RESULTS: Examiners measured 857 PA image sites and 315 BW
      image sites matched on both radiographic systems. Paired t test showed
      significant differences in bone levels between the two systems. Measurements from
      conventional PA images were higher in all maxillary sextants (P < or = .02), and
      measurements from digital PA images were higher in mandibular anterior sextants
      (P = .007). Measurements in digital BW images were higher in mandibular posterior
      sextants (P = .002). A chi2 analysis of categorical bone levels (normal, early-to
      moderate loss or advanced loss) showed significant differences between the
      imaging systems in revealing bone levels in both PA (P < .04) and BW (P < .001)
      images. Digital radiographs showed a higher number of sites with bone loss than
      did conventional radiographs. CONCLUSIONS: Under normal clinical use, alveolar
      bone levels revealed on intraoral direct digital radiographs differ from those
      revealed on conventional radiographs. CLINICAL IMPLICATIONS: Intraoral direct
      digital radiographs are not an equivalent substitute for conventional radiographs
      in evaluating alveolar bone levels.

PMID- 14664266
TI  - A comparison of two intraosseous anesthetic techniques in mandibular posterior
      teeth.
AB  - BACKGROUND: A number of studies have evaluated the Stabident (Fairfax Dental,
      Miami) intraosseous anesthesia technique. A second intraosseous technique--the X
      tip system (X-tip Technologies, Lakewood, N.J.)--has been introduced, but no
      scientific studies have yet compared its effectiveness to that of the Stabident
      system. The authors undertook a study to compare the two systems' anesthetic
      outcomes in primary intraosseous injections in mandibular posterior teeth.
      METHODS: The authors, using a crossover design, randomly administered a primary
      Stabident intraosseous injection and a primary X-tip intraosseous injection, at
      two separate appointments, to 41 subjects. Subjects were asked if they perceived
      an increase in heart rate with the intraosseous injections. The research team
      blind-tested each subject's first molar, second molar and second premolar with a
      pulp tester at two-minute cycles for 60 minutes after the injection. Anesthesia
      was considered successful when two consecutive pulp tester readings of 80 were
      obtained. RESULTS: Anesthetic success rates for the Stabident technique and the X
      tip technique, respectively, were 93 percent and 93 percent for the first molar;
      95 percent and 95 percent for the second molar; and 81 percent and 83 percent for
      the second premolar, with no significant differences (P > .05) between the two
      techniques. For both intraosseous techniques, onset of pulpal anesthesia occurred
      within the first two minutes, but the duration of anesthesia declined steadily
      over the 60 minutes. Eighty-five percent of the subjects had a perceived increase
      in heart rate with the Stabident injection and 93 percent with the X-tip
      injection, with no significant differences (P > .05) between the techniques.
      CONCLUSIONS AND CLINICAL IMPLICATIONS: The two primary intraosseous injection
      techniques were similar regarding anesthetic success, onset, duration and
      perceived heart rate increases.

PMID- 14664267
TI  - An alternative way to use gingival retraction paste.

PMID- 14664268
TI  - Prion disease: possible implications for oral health care.
AB  - BACKGROUND: Prion diseases are a group of rare fatal neurodegenerative disorders
      in humans and animals that are histopathologically characterized by spongiform
      change within the central nervous system. TYPES OF STUDIES REVIEWED: The author
      reviewed all available case reports and any studies of the oral aspects of prion
      diseases published in peer-reviewed journals and available via PubMed. He then
      outlined the risk of nosocomial transmission of prions in dental health care.
      RESULTS: Sporadic Creutzfeldt-Jakob disease, or sCJD, is the most common of the
      acquired human prion disorders, and it typically affects elderly people and leads
      to rapid death. In contrast, variant CJD, or vCJD, has affected young adults from
      Europe, giving rise to a slow onset disorder comprising both psychiatric and
      neurological upset. Oral neurological manifestations are rare and seem to occur
      only in people with vCJD; there are no oral mucosal or gingival manifestations of
      prion disease. Prions can be detected in the oral tissues--usually the gingivae
      and dental pulp--of animals experimentally infected with prions. In contrast,
      prions have not been detected in the pulpal tissue of people with sCJD, and there
      are no data of pulpal infection in vCJD. There also are no data suggesting that
      prions are transmitted easily in the dental setting, but there remains the rare
      risk of such transmission if appropriate infection control measures are not
      adhered to. CLINICAL IMPLICATIONS: Few people in the United States and worldwide
      have prion disease. Oral manifestations are rare. Evidence suggests that the risk
      of transmission and acquisition of a prion infection as a result of dental
      treatment is rare, if appropriate infection control measures are maintained.

PMID- 14664269
TI  - Lack of a scientific basis for routine discontinuation of oral anticoagulation
      therapy before dental treatment.
AB  - BACKGROUND: There is a widespread belief among dental practitioners and
      physicians that oral anticoagulation therapy in which patients receive drugs such
      as warfarin sodium must be discontinued before dental treatment to prevent
      serious hemorrhagic complications, especially during and after surgical
      procedures. OVERVIEW: The authors examine the scientific basis for properly
      managing the dosage of anticoagulants for dental patients who are receiving
      anticoagulation therapy. The authors review the appropriate laboratory test
      values to which dentists should refer when evaluating for dental treatment
      patients who are receiving anticoagulation therapy. The authors also review
      clinical studies, published within the past five years, that focus on the
      frequency and degree of hemorrhagic and related complications among dental
      patients who are receiving anticoagulation therapy orally to prevent
      thromboembolic events. CONCLUSIONS AND CLINICAL IMPLICATIONS: The scientific
      literature does not support routine discontinuation of oral anticoagulation
      therapy for dental patients. Use of warfarin sodium as it relates to dental or
      oral surgical procedures has been well-studied. Some dental studies of
      antiplatelet therapy are consistent with the findings in warfarin sodium studies.
      Dental therapy for patients with medical conditions requiring anticoagulation or
      antiplatelet therapy must provide for potential excess bleeding. Routine
      discontinuation of these drugs before dental care, however, can place these
      patients at unnecessary medical risk. The coagulation status--based on the
      International Normalized Ratio--of patients who are taking these medications must
      be evaluated before invasive dental procedures are performed. Any changes in
      anticoagulant therapy must be undertaken in collaboration with the patient's
      prescribing physician.

PMID- 14664270
TI  - Dental mercury hygiene recommendations.
AB  - BACKGROUND: The ADA has long recognized the importance of observing proper
      mercury hygiene practices for the safety of dental professionals. In 1999, the
      ADA Council on Scientific Affairs adopted mercury hygiene recommendations to
      provide guidance to dentists and their staff members for safe handling of mercury
      and dental amalgam. These mercury hygiene recommendations have been developed to
      update those previously adopted by the Council. OVERVIEW: In addition to
      discussing sources of mercury in the dental office, this Council report describes
      office engineering considerations and hygiene recommendations to be used during
      preparation and placement of dental amalgam restorations. New information
      included in this report covers the management of mercury spills. PRACTICE
      IMPLICATIONS: These recommendations are intended to provide guidance to the
      dental practitioner in ensuring the safety of personnel who handle dental amalgam
      and in minimizing the release of mercury into the dental office environment.

PMID- 14664271
TI  - Value gaps in dental practice: understanding how differences in core values can
      adversely affect the practice.
AB  - BACKGROUND: The authors explore the importance of human values in dental
      practice, an area often overlooked as we struggle to deal with the everyday
      demands of treating patients and managing staff members. Such values are,
      however, fundamental to the success of any practice; therefore, it is important
      to understand their significance. CONCLUSIONS: Problems arise in dental practices
      when gaps develop between the values held by the various players involved (that
      is, between the entire dental team and patients, the dentist/owner's personal
      values and business goals, the dentist/owner and staff members, and the dental
      practice and any third-party funding organizations). PRACTICE IMPLICATIONS: By
      understanding the potentially damaging consequences of value gaps for practice
      viability, dental practice owners and managers can take steps to create a more
      harmonious workplace in which all parties strive to reach common goals.

PMID- 14664272
TI  - Michigan Medicaid's Healthy Kids Dental program: an assessment of the first 12
      months.
AB  - BACKGROUND: In 2000, Michigan's Medicaid dental program initiated Healthy Kids
      Dental, or HKD, a demonstration program offering dental coverage to Medicaid
      enrolled children in selected counties. The program was administered through a
      private dental carrier at private reimbursement levels. The authors undertook a
      study to determine the effect of these changes. METHODS: The authors obtained
      enrollment and utilization data for four groups: children covered in the first 12
      months of HKD in 22 counties, children with private dental coverage in the same
      22 counties in the same 12 months, Medicaid-enrolled children in the same 22
      counties for 12 prior months, and Medicaid-enrolled children in 46 counties who
      were not included in the HKD program at any time. The authors compared access to
      care, dentists' participation, treatment patterns, patient travel distances and
      program cost. RESULTS: Under HKD, dental care utilization increased 31.4 percent
      overall and 39 percent among children continuously enrolled for 12 months,
      compared with the previous year under Medicaid. Dentists' participation increased
      substantially, and the distance traveled by patients for appointments was cut in
      half. Costs were 2.5 times higher, attributable to more children's receiving
      care, the mix of services shifting to more comprehensive care and payment at
      customary reimbursement levels. CONCLUSIONS: By increasing reimbursement levels
      and streamlining administration, the HKD demonstration program has shown that
      substantial improvements can be made to dental access for the Medicaid-enrolled
      population. PRACTICE IMPLICATIONS: The findings of this assessment suggest that
      appropriate attention to administration and payment levels can rapidly improve
      access for Medicaid-enrolled patients using existing dental personnel. By
      cooperating with state officials to design a program that addresses multiple
      issues, dental providers can help create a Medicaid dental program that is
      attractive to both providers and patients.

PMID- 14664273
TI  - What is the role of specialties in dentistry?
AB  - Dental specialties have an important, positive role in improving education and
      practice, stimulating research and defining quality expectations in their areas
      of expertise. However, it is well-known that general dental practitioners
      accomplish a significant portion of the dental therapy that commonly is
      classified as being within the scope of the respective recognized specialty
      areas. In this column, I have made suggestions about methods for improving the
      interaction between specialists and generalists and a call for better acceptance
      by each group of the capabilities of the other.

PMID- 14664274
TI  - The power of values.
AB  - Values are a powerful tool that can be quantified. Once you know your four to six
      business values, you can strengthen your practice and build a high-powered team.
      Once you have completed this exercise, you may want to repeat the process for
      your personal values. It can be insightful and fun.

PMID- 14664275
TI  - The Aetna settlement could be a model for the industry.

PMID- 14664276
TI  - For the dental patient. Receiving antibiotics before dental treatment.

PMID- 14664277
TI  - A COMET lost.

PMID- 14664278
TI  - Chemotherapy-related cardiotoxicity: new diagnostic and preventive strategies.
AB  - Chemotherapy is an established approach for several malignancies, but its utility
      may be hampered by induced cardiac toxicity possibly leading to heart failure,
      with a negative impact on the patient's quality of life and ultimately survival.
      Prospective left ventricular systolic function monitoring has demonstrated that
      cardiotoxicity could be subclinically present for many months or years before its
      overt manifestation. Although considered irreversible, some reports suggested
      recovery or delayed progression of cardiac dysfunction by preventive cardioactive
      therapies. Thus, the identification of earlier instrumental or biochemical
      markers of cardiac injury able to predict heart failure remains a major task.
      Diastolic indexes as a primary expression of hemodynamic dysfunction after
      cardiac damage, analyzed by means of conventional or newer Doppler technologies
      (tissue Doppler, color M-mode, etc.) are discussed. Moreover, brain natriuretic
      peptides, troponins and endothelin-1, as possible sensitive/specific
      markers/predictors of subclinical cardiotoxicity are reviewed in order to update
      and possibly improve the strategy for the detection and clinical management of
      chemotherapy-related cardiotoxic effects.

PMID- 14664279
TI  - The clinical burden of contrast media-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN) is the third cause of acquired acute renal
      dysfunction. The risk of developing a contrast media (CM)-induced nephropathy
      depends on their different physicochemical properties. The iso-osmolality of
      third generation CM lowers the incidence of CM-related renal dysfunction. The
      tubular effect of CM and the hemodynamic changes induced by CM in the renal
      medulla are thought to be the main mechanisms of CIN. The percentage of patients
      at risk has been estimated to range between 3.5 and 15.5% depending on the
      presence of a preexisting impaired renal function, diabetes mellitus, congestive
      heart failure, and hypertension and on the volume of contrast used. Currently,
      only hydration is a generally accepted method of reducing the risk of CIN, and
      further trials are needed to prove the effectiveness of other potential
      prophylactic treatments. Alternatives to ordinary CM, such as carbon dioxide or
      gadolinium chelates, can be used in patients at high risk of CIN undergoing
      peripheral diagnostic or interventional procedures, thus reducing the occurrence
      of CIN.

PMID- 14664280
TI  - Safety and efficacy evaluation of clopidogrel compared to ticlopidine after stent
      implantation: an updated meta-analysis.
AB  - BACKGROUND: Combination therapy with aspirin plus ticlopidine has become the
      reference antithrombotic therapy after coronary stenting. However despite its
      effectiveness, ticlopidine is associated with a significant incidence of severe
      side effects. Thus, clopidogrel, a ticlopidine analogue with an excellent safety
      profile, has been introduced in clinical practice. To date only a few,
      underpowered studies comparing the clinical efficacy of clopidogrel and aspirin
      versus standard combination therapy after coronary stenting have been performed
      and the odds ratios (OR) vary substantially among them. The purpose of the
      present investigation was to update the data regarding this issue by means of a
      formal meta-analysis. METHODS: Ten studies were considered suitable for analysis.
      The OR were calculated for 30 days of follow-up in patients who had undergone
      successful coronary stenting. Primary endpoints were a composite of death and non
      fatal myocardial infarction (MI) (efficacy endpoint) as well as a composite of
      major adverse side effects (safety endpoint) as considered in every single study.
      Secondary endpoints were a composite of major adverse cardiac events, according
      to single study definition, and individual cardiac events as well. RESULTS:
      Overall, 11688 patients were included. At 30 days, the OR for death and non-fatal
      MI was 0.63 (95% confidence interval-CI 0.47 to 0.85, p = 0.003) in favor of
      patients treated with clopidogrel and aspirin. There was also a trend toward less
      major adverse cardiac events (OR 0.83, 95% CI 0.66 to 1.03, p = 0.1), less
      mortality (OR 0.70, 95% CI 0.40 to 1.25, p = 0.2), and less non-fatal MI (OR
      0.76, 95% CI 0.54 to 1.07, p = 0.1). Furthermore, OR for major adverse side
      effects was 0.53 (95% CI 0.42 to 0.66, p < 0.00001) in favor of clopidogrel.
      Similarly, drug intolerance was significantly reduced by clopidogrel (OR 0.51,
      95% CI 0.36 to 0.72, p < 0.0001). Fewer patients on clopidogrel developed
      neutropenia or thrombocytopenia (OR 0.58, 95% CI 0.18 to 1.81, p = 0.3), while
      the incidence of severe bleeding was similar in the two groups (OR 1.19, 95% CI
      0.71 to 1.99, p = 0.5). CONCLUSIONS: The present meta-analysis demonstrates that
      clopidogrel reduces the 30-day combined endpoint of death and non-fatal MI,
      thereby showing a superior clinical efficacy compared to ticlopidine in patients
      who had undergone successful coronary stenting. A significantly better safety
      profile than ticlopidine was also reported, confirming on a larger scale the
      findings of randomized comparative trials.

PMID- 14664281
TI  - Impact of diabetes on the current in-hospital management of heart failure. From
      the TEMISTOCLE study.
AB  - BACKGROUND: Little is known about the clinical profile, use of resources,
      management and outcome of a large population of diabetic patients with heart
      failure managed in a community setting. METHODS: A prospective cross-sectional
      survey in the setting of acute hospital admissions for heart failure to 167
      cardiology and 250 internal medicine departments between February 14 and 25,
      2000. RESULTS: Among the 2127 consecutively admitted patients, 603 (28.4%) had a
      history of diabetes; they were significantly younger, had a lower rate of atrial
      fibrillation, and a more frequent ischemic etiology than non-diabetics. Just as
      non-diabetic patients, diabetics underwent invasive and non-invasive procedures
      in a low percentage of cases, even though slightly more frequently when managed
      by cardiologists. Diabetic patients were less frequently prescribed amiodarone
      and anticoagulants, and more frequently prescribed nitrates and antiplatelets.
      The all-cause in-hospital mortality rate was similar among diabetics and non
      diabetics (5.3 vs 5.7%, p = NS). Adjusted analysis confirmed that diabetes is not
      independently associated with a worse outcome. CONCLUSIONS: In a community
      setting diabetes per se has only a slight impact on the management and outcome of
      patients with heart failure.

PMID- 14664282
TI  - Carotid artery stenting with cerebral protection in 100 consecutive patients:
      immediate and two-year follow-up results.
AB  - BACKGROUND: Carotid artery stenting is emerging as an alternative to surgical
      endarterectomy for the treatment of extracranial carotid artery disease. However,
      few data are available on the long-term clinical efficacy of carotid artery
      stenting and on the incidence of restenosis. METHODS: Stent implantation with the
      routine use of cerebral protection devices was attempted in a single center
      experience including 100 consecutive patients (104 lesions) with significant
      stenosis of the internal carotid artery (mean stenosis 82.8 +/- 9%). The mean age
      of the patients was 70.8 +/- 14 years, 27 lesions were symptomatic (26.0%) with a
      lesion related to a previous stroke or transient ischemic attack. RESULTS:
      Procedural success was achieved in 103 lesions (99%) and the cerebral protection
      was successfully applied in 102 procedures (98%). The 30-day incidence of stroke
      and death was 4% (4 patients). Complications consisted of one major stroke (1%)
      with persistent ipsilateral amaurosis, two minor strokes (2%), and one (1%) fatal
      myocardial infarction occurring 4 days after the stent procedure. During follow
      up (minimum 24 months; mean 31 +/- 6 months) no further neurological events
      occurred, 6 patients died of non-neurological causes (6%) and 2 (2%) presented
      with a non-fatal myocardial infarction. Echo color Doppler scan control (minimum
      24 months) was carried out in all surviving patients showing a restenosis
      classified as moderate (50-69%) in 2 cases and as critical (> or = 70%) in
      another 2 cases (1.8%). Both critical restenotic lesions were successfully
      treated by repeating balloon angioplasty. CONCLUSIONS: The present study
      demonstrates that carotid artery stenting with routine cerebral protection can be
      performed with an acceptable procedural complication rate. At the 2-year follow
      up carotid artery stenting appeared effective in stroke prevention and durable
      with a low incidence of restenosis.

PMID- 14664283
TI  - VDD pacemaker replacement independently of the implanted lead: a prospective
      study.
AB  - BACKGROUND: Single-lead VDD pacing is effective, safe and reliable. The only
      still open, practical issue is represented by the theoretical need of replacing
      each device with a similar one compatible with the already implanted lead to
      guarantee the performance of the system. The aim of our study was to investigate
      the atrial sensing performance of VDD pacemakers working in combination with non
      dedicated chronic leads. METHODS: We enrolled 16 consecutive patients (12 males,
      4 females, mean age 78 +/- 7 years) admitted to our institution for end of life
      of the battery. Atrial dipoles ranged from 5 to 30 mm. All replacements were done
      with a VDD(R) Saphir 3 (Vitatron) designed for an atrial dipole of 8.6 mm.
      RESULTS: All pacemakers were found to be performing well without any complaint by
      the patients imputable to stimulation defects. The P-wave amplitudes measured by
      the old and new pacemakers are similar and respectively 0.64 +/- 0.40 vs 0.73 +/-
      0.53 mV (p = NS). So the old and new devices detect similar P waves. The atrial
      sensing percentage at 1 month of follow-up with the new pacemaker was even better
      than that of the old one (97 +/- 4 vs 95 +/- 3% respectively, p = 0.016): this is
      not imputable to the pacemaker but to the higher programmed atrial sensitivity
      (0.17 +/- 0.06 vs 0.18 +/- 0.07 mV respectively, p = NS). CONCLUSIONS:
      Independently of the implanted lead, the replacement of VDD pacemakers with
      devices designed for a short dipole is feasible, safe and reliable. This
      possibility overcomes a presumed limitation of this pacing modality.

PMID- 14664284
TI  - Left bundle branch block with and without coronary artery disease: which value
      for a tissue Doppler-derived post-systolic motion?
AB  - BACKGROUND: An asynchronous contraction occurring during a prolonged relaxation
      period, defined as post-systolic motion (PSM), has been described as being a
      consequence of coronary occlusion but also in other conditions including isolated
      left bundle branch block (LBBB). The aim of this study was to characterize PSM of
      the interventricular septum at pulsed tissue Doppler in LBBB with or without
      stenosis of the left anterior descending coronary artery (LAD). METHODS: Forty
      two patients with chronic, complete LBBB and tissue Doppler-derived septal PSM
      were divided into two groups on the basis of their coronary angiography: 27
      without LAD stenosis and 15 with LAD stenosis (> or = 50%). Standard Doppler
      echocardiography and tissue Doppler of both the middle posterior septum and
      lateral mitral annulus were performed in the apical 4-chamber view. RESULTS:
      Standard Doppler diastolic indexes were comparable between the two groups. Septal
      tissue Doppler showed lower myocardial systolic (Sm) and atrial peak velocities
      (both p < 0.05), a higher PSM (p < 0.005), and a longer relaxation time (p <
      0.02) and pre-contraction time (p < 0.05) in patients with LAD stenosis. A Sm/PSM
      ratio < 1 was detected in 86% of patients with LAD stenosis and in 22% without
      LAD stenosis (sensitivity 73%, specificity 77%, positive predictive value 64%,
      negative predictive value 84%). Tissue Doppler of the mitral annulus showed a
      significantly longer relaxation time and pre-contraction time and a lower atrial
      velocity in the presence of LAD stenosis. In the overall population, PSM was
      positively associated with ejection fraction and negatively with age and septal
      thickness. In a multiple linear regression analysis, only LAD stenosis (beta =
      0.42, p < 0.005) and ejection fraction (beta = 032, p = 0.03) were independent
      predictors of PSM (cumulative r2 = 0.27, p < 0.002). CONCLUSIONS: Tissue Doppler
      may be useful to distinguish septal myocardial asynchrony in LBBB with and
      without LAD stenosis.

PMID- 14664285
TI  - Drug-eluting versus bare metal coronary stents: long-term human pathology.
      Findings from different coronary arteries in the same patient.
AB  - A 71-year-old woman underwent right coronary artery (RCA) bare metal stenting
      during an acute myocardial infarction. Seven months later the patient received a
      sirolimus-eluting stent as treatment for an 80% left anterior descending coronary
      artery (LAD) stenosis. She remained asymptomatic until she presented with
      unstable angina 16 months later. Angiography demonstrated subtotal occlusion of
      the left obtuse marginal branch. The LAD sirolimus-eluting stent showed 0%
      stenosis. The RCA stent showed 30% restenosis. The left obtuse marginal branch
      lesion was successfully stented, but the patient suffered a fatal stroke 24 hours
      after the coronary intervention. At autopsy the 16-month-old LAD sirolimus
      eluting stent was widely patent with a minute thrombus near the ostium of a small
      side branch. The stent surface appeared free of any other irregularities.
      Scanning light microscopy showed mild neointimal thickening. Scanning electron
      microscopy showed > 80% endothelialization of the stent. The 24-month-old RCA
      bare metal stent showed mild to moderate neointimal growth with > 90%
      endothelialization.

PMID- 14664286
TI  - A brief history of coronary interventional cardiology.

PMID- 14664287
TI  - Infective endocarditis due to Capnocytophaga canimorsus.
AB  - We report the case of a 41-year-old woman with severe mitral regurgitation due to
      infective endocarditis caused by a rare zoonotic microorganism (Capnocytophaga
      canimorsus). She had had a rheumatic mitral endocarditis successfully treated
      with antibiotics when she was 13 years old. She arrived to our attention for a
      fever of unknown origin. She had been bitten by her dog and medicated the wound
      herself. About 2 weeks later she developed a fever with values up to 39.5 degrees
      C. Blood cultures were initially negative but in view of her particular history
      (dog bite), the samples were sent to a specialized center where a Capnocytophaga
      canimorsus (a commensal bacterium contained in the saliva of dogs and cats)
      infection sensitive to ceftriaxone was detected. The antibiotic therapy was
      consequently modified and the patient's fever resolved. At echocardiography a
      mild mitral stenosis with severe regurgitation (3-4+/4+) was detected. We planned
      surgical mitral repair but the operative findings clearly showed the need for
      mitral replacement and a 29 mm size bileaflet mechanical prosthesis was
      implanted. The postoperative course was regular and the patient was discharged on
      the fifth day. We highlight the importance of a careful history and correct work
      up for the diagnosis and treatment of false negative blood culture endocarditis.

PMID- 14664288
TI  - Abciximab for the treatment of an acute thrombotic coronary occlusion during
      stent implantation in a patient with severe hemophilia B.
AB  - Hemophilia B is a severe inherited coagulopathy caused by mutations in the gene
      that encodes factor IX. Surgical and invasive procedures in patients suffering
      from this congenital disease are to be considered as being at high risk of
      hemorrhage. We describe a case of a patient with unstable angina who suffered
      from severe hemophilia B, pre-treated with plasma purified factor IX concentrate
      and not on antithrombotic therapy, in whom the use of abciximab induced the
      complete lysis of an acute thrombus complicating the implantation of a stent on
      the left anterior descending coronary artery.

PMID- 14664289
TI  - Hemophilia and percutaneous coronary interventions.

PMID- 14664290
TI  - [A new model of scientific organization: the Interuniversity Consortium for
      Cardiovascular research].

PMID- 14664291
TI  - [Past, present, and future of intracoronary brachytherapy].
AB  - Intracoronary brachytherapy has been developed as an adjunctive treatment
      strategy for prevention and treatment of restenosis. Two technologies, one
      employing radioactive stents, the other catheter-based radiation systems (beta or
      gamma), have been tested in several animal and human studies in both de novo and
      restenotic coronary lesions. In particular, intravascular ultrasound imaging
      studies have given great insights into the mechanisms of action of intracoronary
      brachytherapy and its complications. Negative results from clinical trials
      performed in patients with de novo coronary lesions and the encouraging results
      obtained with drug-eluting stents have lead intracoronary brachytherapy to be
      abandoned in this clinical context, while it still remains the best therapeutic
      tool for the treatment of patients with in-stent restenosis. In this manuscript,
      principles of radiation therapy, results of clinical trials, current clinical
      practice, and future perspectives of intracoronary brachytherapy are summarized.

PMID- 14664292
TI  - [Hemolysis following valve surgery].
AB  - Hemolysis is a frequent complication of the implant of prosthetic valves, and is
      conditioned by a variety of factors, most of which related to the type of valve
      implanted and to the hemodynamic conditions following implantation. If
      sufficiently severe, it may lead to varying degrees of hemolytic anemia. The
      following laboratory tests are useful to diagnose and assess the severity of
      hemolytic anemia: hemoglobin levels; reticulocyte count; the demonstration of
      schistocytes on a blood smear; serum levels of lactic dehydrogenase, haptoglobin
      and iron. Treatment of hemolysis includes the supplementation of iron and folate
      when their deficiency is evident. Transfusions are necessary only in cases of
      severe anemia refractory to treatment. The use of beta-blockers appears to
      decrease the severity of hemolysis, likely because of the induction of
      bradycardia and of their negative inotropic effects. Some cases have been
      described of erythropoietin treatment for hemolytic anemia in these conditions,
      with favorable outcome. However erythropoietin use should currently be restricted
      to patients with severe hemolytic anemia in whom surgical repair or transfusions
      should be avoided or deferred. The recognition and the estimation of severity of
      hemolysis after valve implantation are important steps in the patients' follow-up
      and the premise for a rational treatment.

PMID- 14664293
TI  - [Chronic thromboembolic pulmonary hypertension].
AB  - Chronic thromboembolic pulmonary hypertension is due to unresolved or recurrent
      pulmonary embolism. In the United States the estimated prevalence is 0.1-0.5%
      among survived patients with pulmonary embolism. The survival rate at 5 years was
      30% among patients with a mean pulmonary artery pressure > 40 mmHg at the time of
      diagnosis and only 10% among those with a value > 50 mmHg. The interval between
      the onset of disturbances and the diagnosis may be as long as 3 years. Doppler
      echocardiography permits to establish the diagnosis of pulmonary hypertension.
      Radionuclide scanning determines whether pulmonary hypertension has a
      thromboembolic basis. Right heart catheterization and pulmonary angiography are
      performed in order to establish the extension and the accessibility to surgery of
      thrombi and to rule out other causes. The surgical treatment is
      thromboendarterectomy. A dramatic reduction in the pulmonary vascular resistance
      can be achieved; corresponding improvements in the NYHA class--from class III or
      IV before surgery to class I-II after surgery--are usually observed. Patients who
      are not considered candidates for thromboendarterectomy may be considered
      candidates for lung transplantation.

PMID- 14664295
TI  - [State of the art of transcatheter ablation for atrial fibrillation].

PMID- 14664294
TI  - [Circumferential isolation of pulmonary veins with transcatheter radiofrequency
      ablation in the treatment of atrial fibrillation].
AB  - BACKGROUND: Circumferential anatomical isolation of the pulmonary veins by
      radiofrequency transcatheter ablation is a new technique for the treatment of
      atrial fibrillation (AF). The aim of our study was to evaluate the efficacy and
      the safety of circumferential radiofrequency ablation of the pulmonary veins and
      to analyze clinical, echocardiographic and procedural parameters as possible
      predictors of clinical success. METHODS: We performed circumferential isolation
      of the pulmonary veins in 33 patients with paroxysmal (15 patients) or persistent
      AF (18 patients) refractory to at least two antiarrhythmic drugs. All patients
      continued antiarrhythmic therapy after the procedure for at least 12 months.
      RESULTS: At the end of the follow-up (mean 13.7 +/- 5.1 months) 70% of the
      patients resulted responders to the ablation, with no differences between
      patients with paroxysmal and persistent AF. Complications were observed in 3% of
      patients. Among clinical, echocardiographic and procedural parameters analyzed
      none turned out to be predictor of clinical success. CONCLUSIONS: Circumferential
      isolation of the pulmonary veins by radiofrequency transcatheter ablation
      associated with antiarrhythmic drugs was efficacious in 70% of patients with
      either paroxysmal or persistent AF. None of the analyzed variables predicted
      clinical success.

PMID- 14664296
TI  - [Network for the treatment of acute myocardial infarction in the province of
      Mantova: results after 2 years of work].
AB  - BACKGROUND: Since June 2001, in the province of Mantova, we have been carrying
      out a program for the management of acute myocardial infarction based on early
      assessment of the patients' risk profile, on telematic connection among care
      centers and on optimization of in- and out-of-hospital critical pathways for the
      access to care. METHODS: Our network provides connection among the following
      centers: advanced life support ambulances, 7 hospitals, 3 coronary care units, 1
      cath lab on call 24 hours a day for primary angioplasty, 1 thoracic surgery
      division. This program, through its strong telematic platform, allows early
      assessment of myocardial infarction, and provides primary angioplasty to all high
      risk patients, being fibrinolytic treatment reserved only to the low-risk
      patients admitted in peripheral hospitals. RESULTS: Two hundred and twenty
      patients with acute myocardial infarction were treated with angioplasty; 179
      (81%) patients underwent primary angioplasty, 26 (12%) patients facilitated
      angioplasty and 15 patients (7%) rescue angioplasty; 121 patients (55%) were
      first admitted in the Mantova hospital, 65 patients (30%) were referred to
      Mantova from peripheral hospitals and 34 patients (15%) were directly transported
      to the cath lab by advanced life support ambulances. Procedural success was
      obtained in 98% of cases, with 05% intraprocedural mortality. In-hospital
      mortality was 55%, while mortality of cardiogenic shock patients was 36%.
      Recurrence of acute myocardial infarction occurred in 1% and major bleeding in
      2.2% of patients. One patient with cardiogenic shock died during transport. Mean
      door-to-balloon time was 73 min with 39% reduction in the second period of
      recruitment after telematic connection. CONCLUSIONS: This program, developed in
      the setting of a provincial network for the management of acute myocardial
      infarction, provided primary angioplasty to all high-risk patients, with a high
      procedural success rate. Within a few months, time to treatment was minimized by
      the employment of telematic facilities.

PMID- 14664297
TI  - [Consensus document. Type B natriuretic peptide in the Italian cardiology
      clinical reality: update of the experience].
AB  - The research on natriuretic peptides in cardiology has now reached the clinical
      setting in cardiology. The scientific literature on the brain natriuretic peptide
      (BNP) or on its N-terminal peptide (NT-proBNP) in heart failure is steadily
      growing, but Italian groups are under-represented in this context, even if there
      are some published or ongoing studies. This document summarizes the experience,
      mostly ongoing and unpublished, of 12 Italian groups in that field, as presented
      in a recent national meeting, suggests recommendations about the collection of
      blood samples and analytical procedures for BNP assay, and presents a brief
      consensus on the use of BNP in heart failure, for different areas: a) population
      screening, b) differential diagnosis of heart failure in case of dyspnea in
      general practice and c) in the emergency room, d) prognostic stratification in
      patients with diagnosed heart failure, and e) hormone-guided treatment of heart
      failure.

PMID- 14664298
TI  - [Papillary fibroelastoma of the septal leaflet of the tricuspid valve. Report of
      a case and review of the literature].
AB  - Papillary fibroelastoma is a rare benign cardiac tumor typically attached to the
      cardiac valves. The tumor is recognized during life, more often in patients
      evaluated for embolic events of unclear pathology, but sometimes also in totally
      asymptomatic patients. There is a general agreement that left-sided
      fibroelastomas must be removed to avoid systemic complications. Right-sided
      localization is even rarer. We report a case of a young woman with a papillary
      fibroelastoma arising from the septal leaflet of the tricuspid valve. It was
      detected by two-dimensional transthoracic echocardiography and confirmed by
      transesophageal echocardiography. To our knowledge, this is the seventeenth
      reported case of a tricuspid valve papillary fibroelastoma, found by means of
      echocardiography. The tumor was successfully treated by complete surgical
      excision, without damage of the tricuspid valve. The best therapeutic strategy to
      be applied in asymptomatic cases is discussed.

PMID- 14664300
TI  - [Open letter to the Italian cardiologists. Response of the SIEC's president].

PMID- 14664301
TI  - [The time for courageous choices].

PMID- 14664299
TI  - [Electrocardiographic picture of a previous myocardial infarction in a patient
      with liver echinococcosis cyst].
AB  - We report a case of a 32-year-old man who was hospitalized at the Department of
      Surgery for hepatic cystic echinococcosis. Standard preoperative
      electrocardiogram revealed the presence of Q waves in the inferior leads,
      suggesting the presence of a previous myocardial infarction. Two-dimensional
      echocardiography showed a hepatic cystic echinococcosis raising the diaphragmatic
      wall of the left ventricle. The electrocardiogram performed the day after surgery
      showed disappearance of Q waves in the inferior leads. Thus, it is suggested that
      the preoperative electrocardiographic picture of a previous myocardial infarction
      was determined by the mass of the hepatic cystic echinococcosis.

PMID- 14664302
TI  - Why do professionals disagree? The case of hormone replacement therapy and
      coronary heart disease prevention.
AB  - Why have professionals disagreed about whether midlife women should be advised to
      use hormone replacement therapy (HRT) for prevention of coronary heart disease
      (CHD)? Because the evidence has been incomplete and could be interpreted
      differently by different professionals, the question with regard to HRT and CHD
      prevention thus is not "What does the evidence prove?" but rather is "What are
      the decision rules by which research can be evaluated and made sense of?" The
      present article attempts to clarify the problem by cataloging dimensions along
      which professionals differ. These dimensions include the weight to be given to
      epidemiological vs. clinical trial data; whether a conclusion has already been
      drawn based on available evidence; whether a theoretical rationale exists;
      whether a professional is oriented to clinical work or research; and whether data
      is distorted.

PMID- 14664303
TI  - Cardiovascular disease risk factors and menopausal status in midlife women from
      the former Soviet Union.
AB  - The purpose of this cross-sectional analysis is to examine modifiable CVD risk
      factors in relation to menopausal status, age, and length of residence in the
      U.S. of midlife women from the former Soviet Union. The analysis includes
      baseline data for 193 women, aged 40-70, who lived in the U.S. fewer than 8 years
      and were enrolled in an ongoing four-year study of post-immigration health and
      behavior change. Data collection was conducted in women's homes or other
      community locations. The presence of seven health risk indicators (obesity,
      dyslipidemia, high blood pressure, diabetes mellitus, sedentary lifestyle,
      smoking, and excessive alcohol use) was assessed. In addition, Framingham 10 year
      risk scores for heart disease, and the presence of metabolic syndrome, were
      calculated using recent National Cholesterol Education Program (ATP-III)
      guidelines. Consistent with the age distribution, 60% of the women were
      postmenopausal. Four risk indicators (obesity, dyslipidemia, high blood pressure,
      and sedentary lifestyle) were identified as significant areas of concern.
      Although the Framingham risk scores did not seem excessively high, almost 25% of
      the women had metabolic syndrome. Older and postmenopausal women had
      significantly higher scores on all risk estimates. When age and menopausal status
      were held constant, menopausal status remained an independent contributor for the
      number of CVD risk indicators. Issues specific to this group of women because of
      their pre- and post-migration lifestyles are discussed in relation to their CVD
      risk status.

PMID- 14664304
TI  - Constructions of femininity and experiences of menstrual distress.
AB  - The purpose of this article is to explore the relationship between constructions
      of feminine gender identity and experiences of menstrual distress. Both
      quantitative and qualitative methods were used to assess the relationship between
      femininity and PMS. Statistically significant correlations were found between T
      scores for femininity on the Bem Sex Role Inventory (Bem, 1978) and total
      distress scores on the Menstrual Distress Questionnaire (Moos, 1991). Analysis of
      the qualitative data suggests that women engage in intense premenstrual bodily
      surveillance, and the data support Ussher, Hunter, and Browne's (2000) findings
      that the 'PMS self' becomes lived as an identity position in contrast to a 'real'
      or 'non-PMS sell.' The authors conclude that our biopsychiatric discourse about
      PMS functions to legitimize traditional constructions of femininity and that
      future research should conceptualize menstrual distress as both lived experience
      and social construction.

PMID- 14664305
TI  - To bleed or not to bleed: young women's attitudes toward menstrual suppression.
AB  - The purpose of this study was to investigate women's knowledge about and
      attitudes toward the medical suppression of menstruation. One hundred and three
      female undergraduate students completed several questionnaires. Thirty-five
      percent of the participants were familiar with menstrual suppression, and 12%
      reported using birth control methods to suppress their menses; oral contraceptive
      users were more knowledgeable about menstrual suppression than other women. Women
      who regarded menstruation as bothersome and shameful were more supportive of
      suppression than women with more positive attitudes. Women who scored higher on
      measures of body consciousness were not more likely to support menstrual
      suppression or to report a desire for more information about menstrual
      suppression. Future investigations of women's attitudes toward menstrual
      suppression could inform reproductive health care and health education.

PMID- 14664306
TI  - Attitudes toward and experience with menstruation in the US and India.
AB  - Sixty-seven women students who were attending a university in southern India and
      61 women students who were attending a liberal arts college in New England
      volunteered to participate in this study. The women supplied demographic
      information, information about their knowledge and levels of preparedness prior
      to menarche, and sources of their information about the menstrual cycle. They
      also completed the Menstrual Attitude Questionnaire (Indian version), the
      Menstrual Distress Questionnaire, and a test of knowledge about the menstrual
      cycle. American women scored significantly higher than Indian women on the
      knowledge test, and they also reported that they had better preparation for
      menarche than Indian women did. Indian women scored significantly higher than
      American women on the attitude subscales: Menstruation as a Natural Event and
      Denial of the Effects of Menstruation. Implications of these findings are
      discussed in light of cultural messages women receive.

PMID- 14664307
TI  - Husbands' support of their perimenopausal wives.
AB  - The purpose of this study was to investigate the social support provided by
      husbands to their perimenopausal wives. Ninety-six husbands of women who were
      participating in the longitudinal Midlife Women's Health Survey answered open
      ended questions concerning how supportive they perceived themselves to be, what
      information they had concerning menopause, and what kinds of stress they were
      experiencing in their own lives. One-third of the husbands believed they were not
      supportive, but the majority said they provided mostly emotional support. Most
      husbands had some information about menopause, but more than one in four knew
      little or nothing. The majority of the husbands got their information from their
      wives. Husbands reported numerous stressors in their lives, including work and
      financial problems and declining health and sexual response. Lack of information,
      negative effects of their wives' menopausal transition, and their own stresses
      may have interfered with husbands' ability to provide social support. Future
      research with a larger and more diverse sample that includes wives as well as
      husbands is recommended.

PMID- 14664308
TI  - Preparation of occupational therapists and physical therapists to work in
      educational settings: the TASH resolution.

PMID- 14664309
TI  - Longitudinal performance of infants with cerebral palsy on the Test of Infant
      Motor Performance and on the Alberta Infant Motor Scale.
AB  - Understanding the natural history of development in children with cerebral palsy
      (CP) is important for studying the consequences of early intervention. The
      purpose of this paper is to present results on the Test of Infant Motor
      Performance (TIMP) from 0-4 months of age and on the Alberta Infant Motor Scale
      (AIMS) from 3 to 12 months of age in a group of infants later diagnosed as having
      CP. Ages at which infants with CP were first recognized as having delayed motor
      performance on each instrument and the stability of performance over time are
      presented. Clinical implications for using both instruments are discussed.

PMID- 14664310
TI  - The effect of conductive education, intensive therapy, and special education
      services on motor skills in children with cerebral palsy.
AB  - PURPOSE: The purpose of this study was to compare the effects of intensive
      therapy, conductive education, and special education on function in 19 children
      with cerebral palsy. METHODS: Subjects participated in a five-week program of
      conductive education, intensive therapy, or special education. Professionals,
      blinded to group assignment, administered the Pediatric Evaluation of Disability
      Inventory (PEDI), the Gross Motor Function Measure (GMFM), and the Fine Motor
      Scale of the Peabody Developmental Motor Scales before and after intervention.
      Professionals providing treatment and parents completed a survey about their
      perceptions of change in the children. RESULTS: ANOVA showed no statistically
      significant differences between groups before or after treatment. Using t-tests,
      statistically significant within group changes were found only for the intensive
      therapy group on the PEDI Self-care and Social Function scales and the Crawling
      and Kneeling scale of the GMFM. Individual changes from pre- to post-test were
      also examined and are discussed. Surveys revealed that both parents and
      professionals perceived improvement in all children. CONCLUSIONS: Greatest
      improvements were noted in the group receiving intensive therapy, with children
      in all groups showing some improvement in function.

PMID- 14664311
TI  - Sensory integration and therapeutic riding at summer camp: occupational
      performance outcomes.
AB  - Occupational performance outcomes from a summer camp for children with sensory
      modulation disorder were examined. Sensory integration based programming was
      incorporated into a one week summer day camp that featured therapeutic riding.
      Using a modified interview format, the Canadian Occupational Performance Measure
      (COPM) was administered to camp participants and their families two weeks prior
      to and one week after camp. Ten families participated in the study. Comparison of
      the families' ratings revealed a significant and positive change in the
      children's behaviors. The COPM was highly useful and provided the opportunity to
      examine the impact of the camp experience from an individual and occupational
      perspective.

PMID- 14664312
TI  - Children's handwriting evaluation tools and their psychometric properties.
AB  - Handwriting is an important area of evaluation for pediatric therapists. In
      selecting a handwriting instrument, therapists must not only consider a child's
      area of handwriting difficulty, but also the psychometric properties of the
      instrument chosen. This paper reviews five commonly used children's handwriting
      evaluation tools: (a) Diagnosis and Remediation of Handwriting Problems; (b)
      Minnesota Handwriting Test; (c) Children's Handwriting Evaluation Scale
      Manuscript; (d) Evaluation Tool of Children' s Handwriting-Manuscript; and (e)
      Test of Legible Handwriting. Each assessment is described including how it is
      administered, the scoring system, the reliability and validity of each
      instrument, and purchase information. The strengths and weaknesses of each tool
      are discussed along with factors affecting handwriting evaluation.

PMID- 14664313
TI  - Lasting amelioration of spatial neglect by treatment with neck muscle vibration
      even without concurrent training.
AB  - OBJECTIVE: It has been shown recently that neck muscle vibration in combination
      with an exploration training leads to lasting amelioration of spatial neglect.
      The present study evaluated whether vibration of the left posterior neck muscles
      alone has the potential to induce lasting reduction in spatial neglect. DESIGN: A
      multiple baseline design was used to control for spontaneous recovery or
      uncontrolled change caused by external events. PATIENTS: Six patients with
      spatial neglect following right hemisphere stroke. METHODS: Daily vibration
      treatment of the left posterior neck muscles for 20 minutes on 10 consecutive
      days. During vibration, patients did not perform any specific activities.
      RESULTS: We observed significant amelioration of spatial neglect after
      terminating the vibration therapy. The improvement was found to be stable at
      follow-up testing about 1.4 years later. CONCLUSION: Vibration of the left
      posterior neck muscles is a useful, non-invasive tool supplementing the
      established methods of spatial neglect treatment. It does not necessarily require
      the patient's co-operation, which is an important advantage especially in the
      early phases of rehabilitation.

PMID- 14664314
TI  - Prognosis for patients with neglect and anosognosia with special reference to
      cognitive impairment.
AB  - OBJECTIVE: To describe prognosis in patients with unilateral neglect,
      anosognosia, or both, within a community based stroke cohort. METHODS: Patients
      (n = 377) were evaluated at baseline for the presence of neglect and anosognosia.
      After 1 year, the level of disability was established in survivors. Predictors
      for death and dependency were examined in multivariate analysis. The following
      independent variables were used: age, consciousness, hemianopia, arm paresis, leg
      paresis, sensory disturbance, aphasia, neglect, anosognosia, diabetes mellitus,
      cardiovascular disease, pre- and post-stroke cognitive impairment. RESULTS: Age,
      consciousness and sensory disturbance predicted death. Post-stroke cognitive
      impairment, neglect, hemianopia, arm paresis and age predicted dependency.
      CONCLUSION: Neglect in the acute phase, which occurs in patients irrespective of
      pre-stroke cognitive level, negatively affects disability after 1 year.
      Anosognosia more often occurs in patients who are cognitively impaired before the
      stroke. These patients often are ADL-dependent already, or become dependent
      because of cognitive impairment, not because of anosognosia.

PMID- 14664315
TI  - Associations between lower limb impairments, locomotor capacities and kinematic
      variables in the frontal plane during walking in adults with chronic stroke.
AB  - OBJECTIVE: The objective was to examine the associations between impairments of
      the paretic limb, locomotor capacities and kinematic variables in the frontal
      plane during walking. DESIGN: Cross-sectional study. SUBJECTS: Ten community
      dwelling individuals with chronic hemiparesis due to a cerebrovascular accident.
      METHODS: Frontal plane kinematics of the shoulders and pelvis were assessed
      during treadmill walking in a gait lab using a videographic system to obtain the
      lateral displacements and lateral accelerations. The percentages of time spent in
      single stance were determined with foot-switches. Index of asymmetry for the
      lateral accelerations and single stance were also calculated. Subject motor and
      functional characteristics were measured by standardised clinical tests. RESULTS:
      Correlation analyses with Pearson product-moment correlation or Spearman's rank
      correlation revealed that, except for spasticity, the clinical scores were
      moderately to strongly associated with frontal kinematics and the single stance.
      In the multiple step-wise regression analysis, only the pelvic lateral
      displacements and the index of asymmetry in single stance were explained at more
      than 70% by the clinical scores with the Time Up and Go test explaining a high
      proportion of the total variance of these frontal parameters. CONCLUSION:
      Findings demonstrated associations between physical impairments, locomotor
      capacities and the frontal kinematics in adults with chronic stroke.

PMID- 14664316
TI  - Use of an integrated care pathway: a third round audit of the management of
      shoulder pain in neurological conditions.
AB  - OBJECTIVES: To complete a third round audit of management of shoulder pain using
      an integrated care pathway, to evaluate pro forma documentation and to determine
      outcome. SUBJECTS AND SETTING: Thirty-four patients with upper limb paresis
      admitted to a rehabilitation unit during a 22-month period had shoulder pain and
      were included in the integrated care pathway. METHODS: Retrospective review of
      pro forma documentation against pre-determined standards. RESULTS: Compared with
      the second round audit, performance against 5 out of 9 standards for initial
      assessment and documentation had improved, and ranged from 56% to 94%.
      Achievement of 9 further standards relating to continued management ranged from
      44% to 97%. Variance was not always well recorded. Shoulder pain resolved or
      improved in 18/34 (53%) of patients. CONCLUSION: Introducing the pro forma
      improved standards of documentation and demonstrated a positive outcome in over
      half the patients. Some problems with developing and maintaining integrated care
      pathways in the context of rehabilitation are discussed.

PMID- 14664317
TI  - Body fat, fitness and level of everyday physical activity in adolescents and
      young adults with meningomyelocele.
AB  - OBJECTIVE: Data on body fat and fitness in adolescents and young adults with
      meningomyelocele are scarce. The aim of this study was to assess body fat and
      fitness in this patient group. In addition, we explored whether the level of
      everyday physical activity is related to body fat and fitness. SUBJECTS AND
      METHODS: Body fat (skinfold thickness), fitness (VO2peak), and everyday physical
      activity (Activity Monitor, based on accelerometry) were measured in 14 patients
      with meningomyelocele (8 men, 6 women; age range 14-26 years). RESULTS: Peak VO2
      was 20-30% lower than reference values and 4 patients were obese. Level of
      everyday activity was related to fitness (rs = 0.65, p = 0.01) but not to body
      fat. CONCLUSION: Young patients with meningomyelocele are at risk for developing
      obesity and have a distinctly subnormal fitness. Level of everyday physical
      activity is related to fitness in this patient group.

PMID- 14664318
TI  - Explaining labor force status following spinal cord injury: the contribution of
      psychological variables.
AB  - OBJECTIVE: To investigate the relative influence of demographic, injury and
      psychological characteristics on the labor force status of people living with
      spinal cord injury. DESIGN: Cross-sectional survey. SUBJECTS: 459 persons who had
      experienced a traumatic spinal cord injury. All participants were patients of 1
      of 2 specialist spinal cord injury services located in south-eastern Australia.
      METHODS: A survey, administered on average of 11.2 years after their injury, was
      used to collect the data. The study's main outcome measure was labor force status
      at the time of survey. Of those invited to participate in the study, 73% agreed
      to do so. RESULTS: Demographic, injury and psychological variables were found to
      explain 30% of the variance in the employment criterion: "in the labor force" vs
      "not in the labor force". Psychological variables contributed significantly to
      the separation of the 2 labor force groups. CONCLUSION: The inclusion of the
      selected psychological variables has advanced the understanding of the factors
      related to return to work following spinal cord injury, however this
      understanding is still not complete. Future efforts in this field would likely
      benefit from the inclusion of additional psychological characteristics, as well
      as environmental factors.

PMID- 14664319
TI  - On prediction of vocational rehabilitation outcome at a Swedish employability
      institute.
AB  - OBJECTIVE: The main objective of this investigation was to identify a set of
      variables usable in early outcome prediction of vocational rehabilitation.
      DESIGN: On commencement of rehabilitation at an employability institute, data
      were sampled using structured interviews and checklists. Two years later the
      subjects were followed up by telephone interviews. SUBJECTS: The study sample was
      all unemployed with a somatic disorder as the cause of vocational disability,
      admitted from October 1995 to December 1996 (n = 149). Of these 109 (73%) agreed
      to participate. METHODS: Initially, data on demography, symptoms,
      expectations/beliefs about future capacity for gainful employment and sense of
      coherence (as an indicator of coping resources) were sampled. At follow-up the
      subjects' vocational situations were recorded. RESULTS: At follow-up, 40% were
      working or employable. Among the about 30 variables included, logistic regression
      showed that having a relatively high belief in vocational return (odds ratio, OR:
      4.6, CI: 1.4-15.4), having a relatively high sense of coherence (OR: 3.5, CI: 1.5
      8.4) and having a relatively high educational level (OR: 2.6, CI: 1.1-6.3) were
      significant predictors of positive outcome. CONCLUSION: In this sample, socio
      psychological and educational aspects were far more predictive of outcome than
      were medical circumstances.

PMID- 14664320
TI  - Epidemiology of substance use disorders in women.
AB  - Significant gender differences exist in the prevalence of substance use disorders
      in the United States. There is a trend among boys and girls aged 12 to 17 years
      toward comparable rates of use and initiation for alcohol, cocaine, heroin, and
      tobacco. If this trend continues, over time there may be a narrowing of the male
      to-female prevalence ratios of substance abuse in the older age groups. This
      possibility is particularly disturbing because women have a heightened
      vulnerability to medical, physical, mental, and social consequences of substance
      use. Women also carry additional unique risks during pregnancy because of the
      effect on neonates. In addition, they have certain gender-specific cancer risks.
      Given this and the declining age of initiation of substance use in women,
      prevention and treatment efforts especially geared toward women (eg, education of
      all medical and paramedical staff, screening in primary care clinics, detection
      of drug use early in pregnancy or before conception, brief interventions and
      treatment programs that integrate women's needs) are exceedingly important to
      stop and ultimately reverse this growing trend.

PMID- 14664321
TI  - Screening and prevention of alcohol and drug use disorders in women.
AB  - Today a variety of treatments are available for women with SUDs. They range from
      psychosocial interventions such as motivational enhancement therapy, cognitive
      behavioral therapy, and 12-step recovery to pharmacotherapies such as
      buprenorphine, methadone, and naltrexone. Although the general public remains
      skeptical of SUD treatment, national studies consistently find it to be both
      clinically and economically efficacious. In Oregon, for example, researchers
      found that every dollar invested in drug treatment saved taxpayers dollars 5.60.
      By the time a woman walks through the door of a drug treatment program, however,
      her disorder is likely to be firmly engrained. The medical practitioner's office
      provides an ideal setting for screening and early identification of high-risk
      alcohol and other drug use and abuse. A variety of reliable and valid self-report
      measures are available. Sadly, however, the majority of health providers still do
      not routinely screen patients for alcohol or drug problems. The consequences can
      be severe, particularly for women. Although efforts have focused on practitioner
      education and strategies to address practical barriers to implementation (eg,
      time, resources), much less attention has focused on the pessimistic views of
      practitioners about SUDs and treatment efficacy. New strategies are needed to
      enhance practitioner feelings of self-efficacy about their ability to identify
      and intervene early in the progression from alcohol use to abuse to dependence.

PMID- 14664322
TI  - Co-occurring psychiatric disorders in women with addictions.
AB  - There is clinically important comorbidity between psychiatric and substance use
      disorders, particularly in women. Women with affective and anxiety disorders are
      more likely to present with alcohol or drug abuse/dependence. In turn, substance
      abusing women are more likely to experience clinically significant depression and
      anxiety. Emerging evidence is pointing to an etiological role for anxiety
      disorders in the development of substance abuse/dependence; however, etiologic
      evidence is not as clear-cut for major depressive disorder. PTSD appears to be a
      particularly important factor for alcohol and drug dependence in women who have
      experienced childhood or adult sexual and or physical abuse. Although
      pharmacotherapy for affective or anxiety disorders is useful for ameliorating
      psychiatric symptoms, research is mixed on the effectiveness for improving
      alcohol- and drug-related outcomes. There is some limited evidence that women
      specific services can improve treatment retention, substance use outcomes, and
      possibly psychosocial functioning compared with traditional mixed-gender
      programs. However, it is clear that women with co-occurring psychiatric and
      substance use problems are challenging to engage and retain in care. Physicians
      providing women's reproductive health services can serve a vital role in the
      identification and referral of substance-abusing women. Particular attention
      should be focused on screening and assessment of alcohol and drug use and problem
      severity among women who have identified psychiatric disorders or who are
      receiving antidepressant or anxiolytic medications. Recognition and referral for
      both psychiatric and substance use disorders are critical for long-term health
      and psychosocial improvement.

PMID- 14664323
TI  - Psychosocial treatments for women with substance use disorders.
AB  - Research on psychosocial treatments for women generally has consisted of quasi
      experimental studies, with few randomized controlled trials that specifically
      test the effectiveness of treatment for women. Review of the available research
      literature suggests the following: (1) women, compared with men, evidence poorer
      prognostic characteristics; (2) women generally do not differ significantly from
      men on treatment utilization or outcome, with the possible exception of
      employment outcomes, which have been found to be poorer for women; and (3) women
      may benefit significantly from enhanced treatment services. This article also
      discusses guidelines for treatment providers and researchers.

PMID- 14664324
TI  - Pharmacology of drugs of abuse.
AB  - The pharmacology of most addictive substances is being studied extensively, not
      just for their acute effects but also the mechanisms that lead to drug seeking
      and addiction. The understanding of how these drugs alter their effects at the
      molecular level with continuing use gives promise toward investigation of novel
      substances that may be used for treatment. Genetic predisposition and gender
      differences are also some of the areas where more research is needed. Women who
      are addicted are likely to continue drug use during pregnancy, which can have an
      impact on the next generation. Prevention measures at the population level are as
      important. Programs need to address risks, social issues, and environmental
      factors that promote drug use and addiction.

PMID- 14664325
TI  - Pharmacologic treatments for women with addictions.
AB  - Physicians have a growing array of pharmacotherapies available for the treatment
      of substance use disorders. These medications are of central importance in the
      treatment of opioid and nicotine dependence and are of growing importance in the
      treatment of alcohol and stimulant dependence. Pharmacotherapy alone is rarely
      sufficient treatment for substance use disorder; appropriate psychosocial
      treatment or mutual help (eg, 12-step) participation is almost always indicated
      whether or not pharmacotherapy is used. Specialized facilities, licensing, and
      training are necessary for the use of some of the pharmacotherapies discussed in
      this article. The obstetrician gynecologist must determine the scope of his or
      her own practice in this area (ie, when to treat and when to refer) based on
      interest, training and experience, and available resources.

PMID- 14664326
TI  - Substance use disorders in women: special considerations during pregnancy.
AB  - Care of substance-using pregnant women is complex, difficult, and often
      demanding. Women's care providers must be aware of these women's unique
      psychologic and social needs and the related legal and ethical ramifications
      surrounding pregnancy. In addition, relating specific substances to perinatal
      outcome is difficult, because concurrent use of multiple substances is frequent
      and many pregnant abusers are members of economically disadvantaged segments of
      society in which unfavorable perinatal outcomes are more common. It is also
      difficult to follow up outcomes in such pregnancies prospectively and to analyze
      research data. This article discusses various issues related to pregnancies
      complicated by substance use, including perinatal pharmacology and teratogenic
      risks, identification of substance abuse, treatment approaches, and comprehensive
      perinatal management.

PMID- 14664327
TI  - Ethical considerations in caring for women with substance use disorders.
AB  - People living with addiction endure many hardships, and this may be especially
      true for women who face distinct clinical and significant psychologic and
      socioeconomic repercussions of addictive disorders and their companion stresses.
      Clinicians who work with women with addictions are confronted by many challenges,
      particularly in the care of pregnant and parenting women. The dilemmas faced by
      patients with addictions and their providers often arise directly from tensions
      among core ethical principles, from inconsistencies in the way these principles
      are applied, and from the pervasive effects of stigma. Although difficult issues
      are to be expected in the arena of substance abuse treatment, consideration of
      principles of voluntarism, beneficence, respect for persons and justice,
      confidentiality and truth-telling, and informed consent are invaluable in shaping
      clinical ethical decision making. Furthermore, proactive steps can be taken to
      enhance the ethical caliber of care. These steps involve policy-level and
      systemic actions, such as the development and expansion of programs serving
      women's unique needs, empiric research into the most effective treatments for
      women with various disorders, and reexamination of legal and societal stances
      toward pregnant and parenting women who have addictions. In addition, local and
      individual steps are needed, including addressing gaps or inherent biases in
      programs, training counselors and clinicians in effective strategies or
      counseling styles, and developing awareness of one's own attitudes when dealing
      with difficult patients and challenging disorders. Such efforts will help ensure
      that women who have addictions will be cared for in a manner that is respectful,
      beneficent, compassionate, honest, and just.

PMID- 14664328
TI  - Obstetrics and gynecology resident education in tobacco, alcohol, and drug use
      disorders.
AB  - Substance use disorders are common problems that all primary care physicians will
      encounter. These disorders have a significant impact on the health of all
      affected women throughout their lifespan. It is important to know the effects of
      drug use on women, so primary care residents need to be prepared to discuss
      substance use disorders with their patients. Residents also need to know that
      brief interventions can reduce risky behaviors even if they do not result in
      abstinence.

PMID- 14664329
TI  - Specific roles of the obstetrician-gynecologist.
AB  - Obstetrician-gynecologists can play a major role in the prevention,
      identification, and treatment of substance abuse in women. Maintaining cognizance
      of abuse potential and consistently using office-screening techniques will
      identify patients who need assistance. Employing brief interventions at frequent
      office visits is an effective means of treating many of these patients. Those who
      do not respond to brief interventions may benefit from referral to an
      addictionologist. The US Supreme Court recently verified the Fourth Amendment
      rights of pregnant women by deciding that consent must be obtained to perform
      drug screening in pregnancy. Obstetrician-gynecologists will need to stay abreast
      of the changes that occur in their state laws as a result of this decision.

PMID- 14664330
TI  - Pharmacological activities and mechanisms of natural phenylpropanoid glycosides.
AB  - The pharmacological activities and mechanisms of action of natural
      phenylpropanoid glycosides extracted from a variety of plants are summarized in
      this review, such as antitumor, antivirus, anti-inflammation, antibacteria,
      antiartherosclerosis, anti-platelet-aggregation, antihypertension, antifatigue,
      analgesia, hepatoprotection, immunosuppression, protection of sex and learning
      behavior, protection of neurodegeneration, reverse transformation of tumor cells,
      inhibition of telomerase and shortening telomere length in tumor cells, effects
      on enzymes and cytokines, antioxidation, free radical scavenging and fast repair
      of oxidative damaged DNA. Molecular modeling is discussed as well as structure
      activity relationships.

PMID- 14664331
TI  - [Isomeric phenanthridines from 1,2-dihydro-5-methyl-2'-nitro-[1,1'-biphenyl]-2,6
      dicarboxylic acid esters].
AB  - Hydrolysis of the dienamine function of the dihydrobiphenyls 3 leads to a mixture
      of the tautomers 4A-C (NMR). The structures of the starting material 3a and the
      products 4cA and 4bC are confirmed by X-ray crystal analysis. The biphenyls 5 are
      formed by dehydrogenation of 3 with iodine, whereas 4b produced the additional
      iodinated compound 6. 4b reacts with manganese dioxide to yield the phenol 7a.
      Irradiation of the dihydrobiphenyls 3 with UV-A light gives the nitrosobiphenyls
      8. In contrast, the nitrobiphenyl 7b and the lactam 10a are formed as photo
      products from 4c. The reduction of the nitro group of 5 with Fe/AcOH leads to the
      isomeric phenanthridines 10 and 11 by cyclization, whereas after reaction with
      Zn/NH4Cl the cyclic hydroxamic acids 12 and 13 are isolated. Compound 7a reacts
      with Zn/acetate buffer to yield only the hydroxamic acid 12. Ring closure takes
      place on treating the nitrosobiphenyls 8 with conc. hydrochloric acid, to yield
      the chloro-substituted hydroxamic acids 14. The half wave potentials of the
      dihydrobiphenyls 3 and 4 are measured by anodic oxidation using a rotating
      platinum electrode by means of differential pulse voltammetry. The dienamines 3
      are more sensitive towards oxidation than the reference drug nifedipine; in
      contrast, the carba-analogues 4 are much more stable. The cyclic hydroxamic acids
      13 and 14a are tested for their ability to inhibit 5-, 12- and 15-lipoxygenase.
      Compound 13 represents a weak inhibitor of 5-lipoxygenase in human whole blood.

PMID- 14664332
TI  - Synthesis of some functionalized arylaminomethyl-1 ,2,4-triazoles, 1,3,4-oxa- and
      thiadiazoles.
AB  - Thiosemicarbazides undergo different cyclization reactions to give five membered
      heterocycles. The product of cyclization depends on the reagent used. This
      cyclization leads to the formation of 1,3,4-oxadiazole, 1,3,4-thiadiazole and
      1,2,4-triazole derivatives. The reaction of thioglycolyl hydrazide derivatives of
      the 1,2,4-triazole compounds was discussed. The activity against hepatitis B
      virus (HBV) has been tested.

PMID- 14664333
TI  - A simple HPLC method for the simultaneous analysis of insulin and ovomucoid.
AB  - An analytical HPLC method is reported for the simultaneous determination of
      insulin and its enzyme inhibitor, chicken ovomucoid. Verapamil was used as an
      internal standard. The elution was achieved using a gradient technique (10-15% B
      for 4 min, 15-35% B from 5th to 11th min and 35-10% B from 12th to 22nd min). The
      mobile phase used was 0.05% v/v trifluoroacetic acid (TFA) in water and 0.05% v/v
      TFA in acetonitrile with a flow rate of 1.2 ml/min. The analytes were detected at
      210 nm after resolution using a reversed phase C-18 column. Insulin, ovomucoid
      and verapamil (IS) were eluted at 11.9, 14.2, and 18 min, respectively, free from
      any interfering endogenous peaks during a run time of 22 min. Linear
      relationships were observed between the detector response and the concentrations
      of the analytes (0.05-1 I.U/ml for insulin (r2 = 0.9975) and 5-100 microg/ml for
      the chicken ovomucoid (r2 = 0.9993)). The assay was found to be highly selective
      and sensitive due to the absence of any interfering peaks. The lower C.V and %
      error values of the assay indicates that the assay could accurately and precisely
      quantitate both insulin and ovomucoid in the examined concentration range. This
      method can be used for the simultaneous quantitation of insulin and chicken
      ovomucoid.

PMID- 14664334
TI  - Application of first derivative UV-spectrophotometry and ratio derivative
      spectrophotometry for the simultaneous determination of candesartan cilexetil and
      hydrochlorothiazide.
AB  - Two-component mixtures of candesartan cilexetil (CAN) and hydrochlorothiazide
      (HYD) were assayed by first derivative and ratio derivative spectrophotometry.
      The first method depends on zero-crossing and peak to base measurement. The first
      derivative amplitudes at 270.1 and 255.5 nm were selected for the assay of (CAN)
      and (HYD), respectively. The second method depends on first derivative of the
      ratio spectra by division of the absorption spectrum of the binary mixture by a
      normalized spectrum of one of the components and then calculating the first
      derivative of the ratio spectrum. The first derivative of the ratio amplitudes at
      236, 250, 232, 267 and 280 nm were selected for the determination of (CAN) and
      (HYD), respectively. Calibration curves were established for 6.0-38.0 microg x
      ml(-1) for (CAN) and 4.0-28.0 microg x ml(-1) for (HYD) in binary mixtures. Good
      linearity, precision and selectivity were found, and the two methods were
      successfully applied to the pharmaceutical dosage form containing the above
      mentioned drug combination without any interference by the excipients.

PMID- 14664335
TI  - Extractive spectrophotometric methods for determination of lercanidipine.
AB  - Extractive spectrophotometric methods are described for the determination of
      lercanidipine (LER) either in pure form or in pharmaceutical formulations. The
      methods involve formation of coloured chloroform extractable ion-pair complexes
      with bromothymol blue (BTB) and bromocresol green (BCG) in acidic medium. The
      extracted complexes showed absorbance maxima at 417 and 416 nm for BTB and BCG,
      respectively. The optimization of the reaction conditions was investigated.
      Beer's law is obeyed in the concentration ranges 6.0-42.0 microg x ml(-1) or 7.1
      43.8 microg x ml(-1) with BTB or BCG, respectively. The composition of the ion
      pairs was found to be 1:1 by Job's method. The specific absorptivities, molar
      absorptivities, Sandell sensitivities, standard deviations and percent recoveries
      were evaluated. Also, LER was determined by measurement of its first derivative
      signals at 245 nm. Calibration graph was established for 4.2-58.0 microg x ml(-1)
      of LER. The methods have been applied to the determination of drug in commercial
      tablets. Results of analysis were validated. No interferences were observed from
      common pharmaceutical adjuvants.

PMID- 14664336
TI  - Dextrans--potential polymeric drug carriers for suprofen.
AB  - Dextrans are clinically useful biodegradable polysaccharide macromolecules and
      have been utilized as carriers for suprofen. Conjugates of suprofen were
      synthesized by preparing their acylimidazol derivatives which were condensed in
      situ with dextrans of different molecular weights (40000, 60000, 110000 and
      200000). The structures of the synthesized conjugates were confirmed by IR and
      NMR spectroscopy. The degrees of substitution obtained were between 7.5 and 9.0%.
      The molecular weight was determined by the Mark-Howin Sakurada viscosity
      equation. Hydrolysis was studied in different buffer solutions (pH 1.2, 7.4, 9.0)
      and 80% human plasma (pH 7.4) and followed first order kinetics. Much faster
      hydrolysis was observed at pH 9.0 compared to pH 7.4 buffer solution and 80%
      human plasma (pH 7.4). Biological evaluation for acute and chronic anti
      inflammatory activity was performed and the results were found to be comparable
      with the parent drug. The ulcerogenic index of conjugates showed a remarkable
      reduction compared to the parent suprofen.

PMID- 14664337
TI  - Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy
      propyl-beta-cyclodextrin.
AB  - The virtual insolubility of gliquidone in water results in poor wettability and
      dissolution characteristics, which may lead to a variation in bioavailability. To
      improve these characteristics of gliquidone, binary systems with hydroxypropyl
      beta-cyclodextrin (HP-beta-CD) were prepared by classical methods such as
      physical mixing, kneading, co-evaporation and co-lyophilization. The solid state
      interaction between the drug and HP-beta-CD was assessed by evaluating the binary
      systems with X-ray diffraction, differential scanning calorimetry and IR-
      spectroscopy. The results establish the molecular encapsulation and amorphization
      of gliquidone. The phase solubility profile of gliquidone in aqueous HP-beta-CD
      vehicle resulted in an A(L) type curve with a stability constant of 1625 M(-1).
      The dissolution rate of binary systems was greater than that of pure drug and was
      significantly higher in the case of co-lyophilized and co-evaporated systems.
      Upon oral administration, [AUC]-alpha was significantly higher in case of co
      lyophilized (2 times) and co-evaporated systems (1.5 times) compared to pure drug
      suspension while other binary systems showed only a marginal improvement. The
      study ascertained the utility of HP-beta-CD in enhancing the oral bioavailability
      of gliquidone, and points towards a strong influence of the preparation method on
      the physicochemical properties.

PMID- 14664338
TI  - The serpins alpha-1-antitrypsin and alpha-1-antichymotrypsin specifically
      interact with immunophilins.
AB  - In a yeast two-hybrid screen FKBP13, a member of the FK506 Binding Protein (FKBP)
      family, was detected to interact with the serpin alpha-1-antichymotrypsin (ACT).
      The specificity of the interaction was confirmed in vitro and by the lack of
      interaction of ACT with FKBP25 and FKBP52. Mutational analysis of ACT revealed
      that the entire protein is necessary to interact with FKBP13. ACT but also
      different unrelated small regions of the ACT protein were able to interact with
      the smaller FKBP12, demonstrating a rather nonspecific interaction with this
      immunophilin. Naturally occuring mutants of ACT were able to interact as well.
      Antitrypsin (AT) closely related to ACT did only interfere with FKBP12 a protein
      that does presumably not reside in the same cellular compartment with AT and ACT.
      Both serpins interacted with the unrelated immunophilin cyclophilin A. In
      conclusion the serpin alpha-1-antichymotrypsin physiologically interacts with the
      ER-immunophilin FKBP13 and the secreted immunophilin cyclophilin A in vivo
      whereas alpha-1-antitrypsin might only react with cyclophilin A; both serpins may
      be controlled thereby in their genuine function.

PMID- 14664339
TI  - Antioxidant properties of dipyridamole as assessed by chemiluminescence.
AB  - The ability of dipyridamole (DIP) to scavenge oxygen metabolites generated by
      either activated human neutrophils (PMNs) or cell-free systems using luminol(s)-
      and lucigenin-enhanced chemiluminescence was investigated. In the presence of DIP
      (15-50 microM) a dose-dependent inhibition period was seen in phorbol myristate
      acetate (PMA)-stimulated PMNs as assayed by isoluminol-enhanced chemiluminescence
      (ILCL) with horseradish peroxidase (HRP). Although such a lag period was not
      observed in the absence of HRP, 50 microM DIP inhibited extracellular ILCL by
      more than 50%. Intracellular luminol-enhanced chemiluminescence (LCL) as assayed
      in either PMA- or in ionomycin-activated PMNs was not affected by dipyridamole
      (15-50 microM). In cell-free systems, DIP produced concentration-dependent
      inhibition in H2O2-(45% at 50 microM), OH- (40%, at 0.1 microM) and HOCl-(20% at
      10 microM). Both absorbance and fluorescence scans revealed that DIP is able to
      react with equimolar quantities of either H202 or HOCl. These results suggest
      that DIP scavenges reactive oxygen species (ROS) presumably secreted by activated
      human PMNs in the following decreasing order: *OH > HOCl > H2O2 >> O2-.

PMID- 14664340
TI  - The effect of disinfectants on Plesiomonas shigelloides.
AB  - The effects of ten commercially available disinfectants on virulence associated
      properties of Plesiomonas shigelloides were tested. All the disinfectants tested
      contained quaternary ammonium salts. The majority of the disinfectants when used
      at subinhibitory concentrations increased surface hydrophobicity as evaluated by
      bacterial adherence to xylene and decreased bacterial motility in a concentration
      dependent manner. Disinfectants did not significantly affect lipase activity.
      However, more than half of the antimicrobials tested increased the resistance of
      bacteria to hydrogen peroxide. The disinfectants, in a similar manner to
      antibiotics at concentrations below MIC, interfered with potential virulence
      factors of Plesiomonas shigelloides.

PMID- 14664341
TI  - Hypolipidaemic effect of Casearia esculenta root extracts in streptozotocin
      induced diabetic rats.
AB  - The hypolipidaemic effect of an aqueous extract of Casearia esculenta root, an
      indigenous antidiabetic medicine popularly used in rural South India was
      investigated. Administration of the extract of C. esculenta (200 and 300 mg/kg
      body wt.) for 45 days resulted in significant reduction in serum and tissue
      cholesterol, phospholipids, free fatty acids and triglycerides in streptozotocin
      (STZ) diabetic rats. In addition to that, significant (p < 0.05) decrease in high
      density lipoprotein (HDL) whereas significant increase (p < 0.05) in low density
      lipoprotein (LDL) and very low density lipoprotein (VLDL) were observed in STZ
      diabetic rats, which was normalized after 45 days of C. esculenta root extract
      treatment. The root extract at dose of 300 mg/kg body wt. showed much significant
      hypolipidaemic effects than the dose of 200 mg/kg body weight.

PMID- 14664342
TI  - Phenolic compounds from Anaphalis aureo-punctata.
AB  - From the ethanolic extract of the whole plant of Anaphalis aureo-punctata, a new
      acylated flavonoid glycoside 3-O-kaempferol-3-O-acetyl-6-O-(p-coumaroyl)-beta-D
      glucopyranoside (1), and five known phenolic compounds were isolated. Their
      structures were established by spectral methods (UV, IR, MS, 1D, 2D-NMR). The
      flavonoid glycosides, 1, 2 and 3 showed markedly inhibited oxidative DNA strand
      breaks induced by Fenton reaction and NADH/PMS in a concentration-dependent
      manner.

PMID- 14664343
TI  - [A new synthesis method for pyrido[1,2-a]thieno[3,2-d]pyrimidine].

PMID- 14664344
TI  - Comparison of the Gordon-Taylor and Couchman-Karasz equations for prediction of
      the glass transition temperature of glass solutions of drug and
      polyvinylpyrrolidone prepared by melt extrusion.

PMID- 14664346
TI  - Changes in heart rate after application of newly developed ultrashort acting beta
      adrenergic blockers.

PMID- 14664345
TI  - Effect of itraconazole on the pharmacokinetics of celecoxib in healthy human
      volunteers.

PMID- 14664347
TI  - Leadership in troubled times.

PMID- 14664348
TI  - Gender in veterinary medicine.

PMID- 14664349
TI  - Veterinarians' salaries: gender differences real or imagined?

PMID- 14664350
TI  - An ethicist's commentary on funding animals for continuing education.

PMID- 14664352
TI  - Survey of the status of copper, interacting minerals, and vitamin E levels in the
      livers of sheep in Ontario.
AB  - Livers from cull ewes and market lambs raised in Ontario were obtained to
      determine the status of specific minerals and vitamin E. Values for copper (Cu),
      iron (Fe), manganese (Mn), and zinc (Zn) obtained by atomic absorption and
      inductively coupled plasma--atomic emission spectroscopy (ICP-AES) were found to
      be statistically different but sufficiently biologically similar to allow the use
      of ICP-AES for screening groups of samples for deficient or toxic levels of those
      minerals. Toxic levels of cadmium were not found. Toxic levels of aluminum were
      found in 1 cull ewe and 1 market lamb. A significant proportion of both market
      lamb samples (40.0%) and cull ewe samples (50.0%) had high to toxic levels of Cu.
      In market lambs, Fe, Mn, molybdenum (Mo), selenium (Se), and Zn were not found to
      be important determinants of Cu level. In cull ewes, Fe, Mn, and Zn play a
      moderate role in the variability of liver Cu levels. Selenium was found to be
      present at marginal levels in 3.3% of cull ewe samples and in 42.6% of market
      lamb samples. Vitamin E was found to be low to deficient in 10.0% of cull ewe
      samples and in 90.0% of market lamb samples. In market lambs, only Mo was
      associated with Se levels, and no minerals were associated with vitamin E levels.
      In cull ewes, there was a strong association between Se and vitamin E. This
      survey demonstrates that marked nutritional imbalances of Cu, Se, and vitamin E
      exist in cull ewes and market lambs in Ontario.

PMID- 14664351
TI  - A review of the physiological effects of alpha2-agonists related to the clinical
      use of medetomidine in small animal practice.
AB  - Medetomidine is a relatively new sedative analgesic drug that is approved for use
      in dogs in Canada. It is the most potent alpha2-adrenoreceptor available for
      clinical use in veterinary medicine and stimulates receptors centrally to produce
      dose-dependent sedation and analgesia. Significant dose sparing properties occur
      when medetomidine is combined with other anesthetic agents correlating with the
      high affinity of this drug to the alpha2-adrenoreceptor. Hypoventilation occurs
      with medetomidine sedation in dogs; however, respiratory depression becomes most
      significant when given in combination with other sedative or injectable agents.
      The typical negative cardiovascular effects produced with other alpha2-agonists
      (bradycardia, bradyarrhythmias, a reduction in cardiac output, hypertension +/-
      hypotension) are also produced with medetomidine, warranting precautions when it
      is used and necessitating appropriate patient selection (young, middle-aged
      healthy animals). While hypotension may occur, sedative doses of medetomidine
      typically raise the blood pressure, due to the effect on peripheral alpha2
      adrenoreceptors. Anticholinergic premedication has been recommended with alpha2
      agonists to prevent bradyarrhythmias and, potentially, the reduction in cardiac
      output produced by these agents; however, current research does not demonstrate a
      clear improvement in cardiovascular function. Negatively, the anticholinergic
      induced increase in heart rate potentiates the alpha2-agonist mediated
      hypertension and may increase myocardial oxygen tension, demand, and workload.
      Overall, reversal with the specific antagonist atipamezole is recommended when
      significant cardiorespiratory complications occur. Other physiological effects of
      medetomidine sedation include; vomiting, increased urine volumes, changes to
      endocrine function and uterine activity, decreased intestinal motility, decreased
      intraocular pressure and potentially hypothermia, muscle twitching, and cyanosis.
      Decreased doses of medetomidine, compared with the recommended label dose, should
      be considered in combination with other sedatives to enhance sedation and
      analgesia and lower the duration and potential severity of the negative
      cardiovascular side effects. The literature was searched in Pubmed, Medline,
      Agricola, CAB direct, and Biological Sciences.

PMID- 14664353
TI  - Health status and risk factors associated with failure of passive transfer of
      immunity in newborn beef calves in Quebec.
AB  - Risk factors associated with failure of passive transfer of immunity (FPT) were
      evaluated among newborn beef calves in Quebec. Physical examination was performed
      on calves born of a normal calving and blood samples were collected for
      determination of health status and measurement of serum concentration of
      immunoglobulin (Ig) G1. Of 225 calves, from 45 herds, 19% showed FPT (serum IgG1
      concentration < 10.0 g/L). Calves born in a stanchion-stall were more likely to
      show FPT (OR: 10.2). Calves bottle-fed colostrum were less at risk for FPT (OR:
      0.06). Calf gender, month of birth, dam parity, and dam body condition score were
      not associated with FPT. No association was detected between FPT and health
      status. Special care should be given to calves born from cows in a stanchion
      stall to ensure adequate colostrum intake. Failure of passive transfer of
      immunity should be considered with other risk factors when investigating
      morbidity.

PMID- 14664354
TI  - Electrocardiographic evolution in cats from birth to 30 days of age.
AB  - Further knowledge of feline physiology and neonatology is needed because the
      number of cats being kept as pets and used as experimental animals has increased.
      Few studies have been published on feline sequential electrocardiography. This
      study was conducted to determine the values of normal waves, complexes, and
      intervals of the electrocardiogram in clinically healthy feline neonates. Serial
      electrocardiography was performed in 15 female and 15 male neonates at 30 days of
      age. Parameters analyzed were heart rate and rhythm, duration and amplitude of
      electrocardiographic waves, duration of intervals, and the electrical axis of the
      heart. The results did not show differences between males and females. During the
      neonates' first 30 days of life, migration of the electrical axis from right to
      left was observed. There was a progressive increase in the R wave amplitude,
      while the S wave amplitude showed a progressive decrease. A sinus heart rhythm
      was predominant in the feline neonates.

PMID- 14664355
TI  - Pancreatic insulin-secreting neoplasia in a 9-year-old Afghan hound.
AB  - An Afghan hound was presented with recurring episodes of weakness progressing to
      seizures after exercise. Insulinoma was diagnosed by demonstrating excessive
      insulin secretion in the presence of hypoglycemia. A pancreatic mass was
      identified and removed during an exploratory laparotomy. Surgical and
      pathological findings, diagnosis, and clinical management are discussed.

PMID- 14664356
TI  - Diabetes mellitus in a 6-month-old Charolais heifer calf.
AB  - This unthrifty heifer calf was thin, weak and had a dull haircoat. Urinalysis and
      blood work revealed glycosuria, ketonuria, hypoproteinemia, and hyperglycemia.
      Euthanasia and necropsy were performed, revealing multifocal intersitial
      lymphocytic infiltration, an absence of islet cells, and a positive stain for
      bovine viral diarrhea virus in the pancreas.

PMID- 14664357
TI  - Good practice means using established and emerging resource bases.

PMID- 14664359
TI  - Diagnostic ophthalmology. Congenital medial canthal cyst.

PMID- 14664358
TI  - Salivary mucocele in a wild cat.

PMID- 14664360
TI  - Editorial to the special issue on drowning prevention.

PMID- 14664361
TI  - The epidemiology of drowning worldwide.
AB  - The purpose of this analysis was to quantify the magnitude of death and
      disability from drowning and near-drowning worldwide and to provide
      epidemiological data on which to base prevention efforts. All data are from the
      Global Burden of Disease 2000 (Version 1) estimates in which deaths and
      disabilities are based on the WHO International Classification of Diseases.
      Extrapolations were made by age, sex, and WHO region. The six WHO regions of the
      world were further divided into high-income, and low- and middle-income based on
      the 1998 World Development indicators. According to the GBD 2000 data, an
      estimated 449,000 people drowned worldwide (7.4 per 100,000 population) and a
      further 1.3 million Disability Adjusted Life Years (DALYs) were lost as a result
      of premature death or disability from drowning. 97% of drownings occurred in low-
      and middle-income countries. Although 38% of drownings occurred in the Western
      Pacific Region, Africa had the highest drowning mortality rate (13.1 per 100,000
      population). Males had higher drowning mortality rates than females for all ages
      and in all regions. Children under the age of 5 years had the highest drowning
      mortality rate for both sexes in all of the WHO regions except for Africa, where
      children aged 5 to 14 years had the highest mortality rate. Worldwide, for
      children under the age of 15 years, drowning accounted for a higher mortality
      rate than any other cause of injury. Drowning is a significant problem worldwide
      particularly for children under the age of 15 years. Low- and middle-income
      countries have the highest rates of drowning and account for more than 90% of
      such fatalities. Primary prevention efforts should thus be focused on these
      countries where many children who cannot swim drown in large bodies of water.

PMID- 14664362
TI  - Risk assessment and perception.
AB  - Injury prevention efforts often focus on reducing the risk of potentially
      dangerous activities, facilities or equipment, such as diving, swimming pools or
      flotation devices. This paper aims to clarify the concepts of risk assessment and
      risk perception. Statistically, risk denotes the probability of an untoward
      event, often expressed in terms of potential financial loss. Subjectively,
      though, risk denotes an individual's perception of the likelihood and the
      seriousness of an undesirable event. Individual perception appears to be strongly
      influenced by personal traits and socio-cultural parameters. Risk assessment
      helps to form the basis for public health interventions. The implementation and
      effectiveness of these are influenced by individual risk perception. Therefore,
      preventive efforts need to incorporate and hopefully influence the determinants
      of risk perception among the target populations. Considering drowning, both
      hazard and incidence of submersion injuries are underestimated, whereas treatment
      options are usually overestimated. Consequently, individual risk alertness needs
      to be improved--drowning remains a ubiquitous risk.

PMID- 14664363
TI  - Death from drowning: defining a new challenge for child survival in Bangladesh.
AB  - The study focuses on children less than 5 years old and explores the
      epidemiological profile and correlates of drowning as a challenge to child
      survival in Bangladesh. Two data sources from Bangladesh, a cohort of 8,070
      children followed for 2 years in a rural area and a nation-wide survey conducted
      in 1996-97 have been used. In addition, a systematic review of the literature has
      been conducted spanning the past two decades for analysis of drowning in
      children. Seventy drowning deaths were reported in the cohort and 726 deaths were
      reported in the national survey. Verbal autopsy and semi-structured interviews
      were conducted on all deaths. Drowning accounted for 43% of deaths in the cohort
      and 20% of deaths in 1-4-year-old children in the national survey. Most drowning
      deaths were in 12-23 month old children from falling into ditches and ponds.
      Communities provided valuable insights on possible interventions to reduce deaths
      due to drowning. Drowning is a newly recognized challenge for Bangladesh.
      Considerable research and programmatic work is required to understand the nature
      of the problem and develop appropriate interventions. This paper calls on aid
      agencies to create opportunities for drowning research and action in their work
      plans for the country.

PMID- 14664364
TI  - Swimming lessons, swimming ability, and the risk of drowning.
AB  - Drowning is a leading cause of injury related death in many countries. Strategies
      to prevent these deaths depend upon characteristics of the victim and the
      specific circumstances surrounding the event. One preventive strategy that may be
      beneficial for persons of all ages and under nearly all circumstances is
      increased swimming ability, through some form of swimming instruction. However, a
      clear protective relationship between increased swimming ability and the risk of
      drowning has never been demonstrated. Studies focused on children, suggest that
      swimming ability may confer some protection, although the data are far from
      conclusive. This paper (1) reviews the current evidence regarding the
      relationship between swimming ability, swimming lessons and the risk of drowning,
      (2) reviews the past and present recommendations for swimming instruction and (3)
      outlines future research needs.

PMID- 14664365
TI  - Preventing drowning through design--the contribution of human factors.
AB  - A number of routes can be followed towards the prevention of drowning, such as
      educating on water safety, installing barriers between non-intended users and
      water, mitigating the consequences of submersion incidents, and design. The human
      factor approach to safety is that design should always be the primary route.
      Human factors can be applied to the design of personal protective equipment such
      as buoyancy aids, barriers such as pool fencing, ancillary equipment such as
      swimming pool covers through to information and organisational factors such as
      safety signs and swimming campaigns. Design should consider all potential
      drowning scenarios and accommodate the characteristics of those at risk. A
      framework is presented with examples on how human factor principles can be
      applied to the design of potential drowning sites and products, with suggestions
      for methods and techniques that can be used in the key stages of predicting
      potential hazards and assessing risk.

PMID- 14664366
TI  - Prevention of drowning in home pools--lessons from Australia.
AB  - As an affluent and warm weather country, Australia faced an epidemic of drowning
      in children under five as the popularity of home pools increased in the late
      1960s and early 1970s. In one state child drowning rose by 6.62 per 100,000 in
      the five years from 1968. Variation across jurisdictions in actions to regulate
      domestic pools has resulted in Australia representing an unfortunate natural
      experiment in interventions to prevent child drowning in pools. Mechanisms
      adopted by various authorities were analysed in detail to identify factors that
      contributed to success and failure in regulating domestic pools. Despite early
      identification of the problem and development of what were later demonstrated to
      be effective interventions, best practice solutions were not established in any
      jurisdiction until 2002, 25 years after identification of the problem. Key
      failures in intervention were found to be: failure to act in a timely way, flawed
      regulation, blockage of timely action and repeal of effective state regulation
      under political pressure, and blockage of effective standards. Lessons are
      identified as: inherent weaknesses in the standard setting process, failure of
      interventions to address major risk categories, failure to act before the hazard
      grew, failure to consider lesser interventions for tactical reasons, failure to
      pay attention to advocates, and the need for continuing effort. The paper argues
      that analysis of the identification of the problem, development of interventions
      and implementation of mechanisms of prevention illustrate where systemic changes
      are required and indicate lessons that should be applied in developing and
      implementing future interventions.

PMID- 14664367
TI  - Maritime accident investigation methodologies.
AB  - Whenever a naval disaster occurs, a public outcry is heard to a full
      investigation into the causes of the event. Although the maritime industry has an
      outstanding reputation in accident investigation, such investigations are hardly
      conducted in inland shipping or leisure craft sailing. Due to a number of serious
      accidents in the maritime sector and increasing interest by public and media, the
      philosophy of independent investigations has gained interest at a policy making
      level in the European Union and with international NGO's, such as the
      International Maritime Organization IMO. The purpose of this paper is to discuss
      the application of this methodology in all segments of shipping. The paper
      elaborates a conceptual model, principle processes and available techniques as a
      common orientation to safety-focused investigations. Accident investigation
      reports of Dutch investigative agencies are benchmarked to this model assessing
      the potential of the approach to all segments of shipping. It shows the
      applicability to minor as well as major accidents and the importance of
      independence. Systemic deficiencies at all levels in safety of shipping are
      identified and a generic applicability is demonstrated. It is concluded that
      independent accident investigation provides a powerful diagnostic tool for
      reducing the peril of drowning.

PMID- 14664368
TI  - Epidemiology of squash injuries requiring hospital treatment.

PMID- 14664369
TI  - Gender and geographic differences in intentional and unintentional injury
      mortality among children in Illinois, 1988-1998.

PMID- 14664370
TI  - Climbing injuries in the Netherlands.

PMID- 14664371
TI  - Preventive product safety--monitoring accidental injuries related to consumer
      products in the European Union.

PMID- 14664372
TI  - The use of electronic messages to promote seat belt use. Report of a pilot study
      in Wisconsin.

PMID- 14664373
TI  - Feasibility of routine collection of injured worker occupational information in
      hospital emergency departments.

PMID- 14664374
TI  - Diversity-oriented synthesis; a challenge for synthetic chemists.
AB  - The efficient, simultaneous synthesis of structurally diverse compounds, better
      known as diversity-oriented synthesis (DOS), is not obvious, and remains a
      challenge to synthetic chemistry. This personal account details why DOS has such
      enormous implications for the discovery of small molecules with desired
      properties, such as catalysts, synthetic reagents, biological probes and new
      drugs, Also, I describe the evolution behind the current state-of-play of DOS.

PMID- 14664375
TI  - Highly enantioselective alkaloid synthesis via ene-type cyclizations catalyzed by
      cationic chiral palladium(II) complexes of PN-ligands with an achiral oxazoline
      unit.
AB  - A highly efficient asymmetric alkaloid synthesis via ene-type cyclizations
      catalyzed by cationic chiral palladium(II) complexes of PN-ligands with an
      achiral gem-dimethyl oxazoline unit is shown to give 5-membered products with a
      quaternary carbon center, including a spiro-amide, almost quantitatively with
      extremely high enantiomeric excesses.

PMID- 14664376
TI  - Rapid NMR screening of chloride receptors: uncovering catechol as a useful anion
      binding motif.
AB  - This paper reports the application of a high-throughput 1H NMR screening method
      to the evaluation of potential anion receptors, and the results of the screening
      indicate that catechol is a surprisingly good host for chloride anions.

PMID- 14664377
TI  - Functionalization of the alicyclic skeleton of epibatidine: synthesis and
      nicotinic acetylcholine receptor binding affinities of epibatidine analogues.
AB  - A novel method for the epimerization of endo-2-(6-chloro-3-pyridyl)-7
      azabicyclo[2.2.1]heptan-3-one (12) on silica gel was developed and used as the
      key step to synthesize functionalized analogues of epibatidine which were
      evaluated for their nicotine receptor subtype selectivity in binding studies.

PMID- 14664378
TI  - Amphotericin B-phospholipid covalent conjugates: dependence of membrane
      permeabilizing activity on acyl-chain length.
AB  - The interaction between amphotericin B and phospholipid upon forming ion channels
      across a biomembrane was investigated using their covalent conjugates. The
      membrane permeabilizing activity was greatly affected by the chain length of the
      fatty acyl groups, suggesting that their interaction is involved in ion channel
      assemblages.

PMID- 14664379
TI  - Structure-function relationships in glutathione and its analogues.
AB  - The results are presented of measurements of protonation constants (potentiometry
      and NMR), UV spectroscopic properties and redox potentials of GSH and its five
      analogues, which are modified at the C-terminal glycine residue (gammaGlu-Cys-X,
      X = Gly, Gly-NH2, Gly-OEt, Ala, Glu, Ser). Strong linear correlations were found
      between various properties of the thiol and other functions of these peptides.
      These results allow discussion of the relationships between the structures and
      properties in glutathione and its analogues, and provide a novel chemical
      background for the issue of control of GSH reactivity.

PMID- 14664380
TI  - Chemo-enzymatic synthesis of conformationally constrained oligosaccharides.
AB  - N-Acetyllactosamine derivative 4, which has a methylene amide tether between C-6
      and C-2', was enzymatically glycosylated using rat liver alpha-2,6
      sialyltransferase (ST6GalI) or recombinant human fucosyltransferase V (FucT-V) to
      give conformationally constrained trisaccharides 5 and 6, respectively. The
      methylene amide linker of 4 was installed by a two-step procedure, which involved
      acylation of a C-6 amino function of a LacNAc derivative with chloroacetic
      anhydride followed by macrocyclization by nucleophilic displacement of the
      chloride by a C-2' hydroxyl. The conformational properties of 4 were determined
      by a combination of NOE and trans-glycosidic heteronuclear coupling constant
      measurements and molecular mechanics simulations and these studies established
      that the glycosidic linkage of 4 is conformationally constrained and resides in
      only one of the several energy minima accessible to LacNAc. The apparent kinetic
      parameters of transfer to LacNAc and conformationally constrained saccharides 3
      and 4 indicates that fucosyltransferase V recognize LacNAc in its A-conformer
      whereas alpha-2,6-sialyltransferase recognizes the B-conformer of LacNAc.

PMID- 14664381
TI  - Oligonucleotide duplexes containing N8-glycosylated 8-aza-7-deazaguanine and self
      assembly of 8-aza-7-deazapurines on the nucleoside and the oligomeric level.
AB  - The 8-aza-7-deazaguanine N8-(2'-deoxy-beta-D-ribofuranoside) (1) was synthesized,
      converted into the phosphoramidite 4 and incorporated into oligonucleotides.
      Nucleoside 1 forms stable base pairs with 2'-deoxy-5-methylisocytidine in DNA
      with antiparallel chain orientation (aps) and with 2'-deoxycytidine in duplexes
      with parallel chains (ps). According to the CD spectra self-complementary
      oligonucleotides d(1-m5isoC)3 and d(1-C), form autonomous DNA-structures. Neither
      the nucleoside 1 nor the regularly linked 8-aza-7-deaza-2'-deoxyguanosine form G
      like tetrads while the regularly linked 8-aza-7-deaza-2'-deoxyisoguanosine gives
      higher molecular assemblies which are destroyed by bulky 7-bromo substituents.
      This was verified on monomeric nucleosides by ESI-MS spectrometry and on
      oligonucleotides by HPLC analysis.

PMID- 14664382
TI  - First demonstration of differential inhibition of lectin binding by synthetic tri
      and tetravalent glycoclusters from cross-coupling of rigidified 2-propynyl
      lactoside.
AB  - The interplay of mammalian lectins such as galectins with cellular
      glycoconjugates is intimately involved in crucial reaction pathways including
      tumor cell adhesion, migration or growth regulation. These clinically relevant
      functions explain the interest in designing glycoclusters with potent activity to
      interfere with lectin binding. In view of the perspective for medical
      applications the following objective arises: to correlate topological factors of
      ligand display most favorably to reactivity against endogenous lectins. To date,
      plant agglutinins have commonly been used as models. Properly addressing this
      issue we first prepared di- to tetravalent clusters from 2-propynyl lactoside
      under mild oxidative homocoupling conditions and using the Sonogashira palladium
      catalyzed cross-coupling reaction with triiodobenzene or pentaerythritol cores.
      These products were tested for bioactivity in a competitive solid-phase assay
      using different labeled sugar receptors as probes, i,e. the beta-trefoil
      mistletoe lectin, the natural lactoside-binding immunoglobulin G fraction from
      human serum and three mammalian galectins from two subgroups. The lactose
      headgroups in the derivatives retained ligand properties. Differences in
      inhibitory capacity were marked between the galectins. In contrast to homodimeric
      proto-type galectins-1 and -7 significant inhibition of galectin-3 binding with a
      7-fold increase in relative potency was observed for the trivalent compound. In
      comparison, the binding of the beta-trefoil mistletoe agglutinin was reduced best
      by tetravalent substances The result for galectin-3 was independently confirmed
      by haemagglutination and cytofluorometric cell binding assays. These data
      underline the feasibility of galectin-type target selectivity by compound design
      despite using an identical headgroup (lactose) in synthesis.

PMID- 14664383
TI  - Synthetic studies towards the phomactins. Concise syntheses of the tricyclic
      furanochroman and the oxygenated bicyclo[9.3.1]pentadecane ring systems in
      phomactin A.
AB  - A concise synthesis of the tricyclic furanochroman unit 3 found in the PAF
      antagonist phomactin A (1) isolated from the marine fungus Phoma sp., is
      described. In complementary studies, a variety of synthetic routes towards the
      bicyclo[9.3.1]pentadecane ring system 4 in phomactin A were explored. These
      studies culminated in a synthesis of the substituted ring system 79 containing
      all the carbon atoms and all the necessary oxygen centres for elaboration to
      phomactin A itself.

PMID- 14664384
TI  - A total synthesis of (+/-)-phomactin A.
AB  - A total synthesis of the PAF antagonist phomactin A (1), isolated from the marine
      fungus Phoma sp. is described. The synthesis is based on a Cr(II)/Ni(II)
      macrocyclisation from the aldehyde vinyl iodide 14, leading to the key
      phomactatrienol intermediate 16a, followed by elaboration of 16a to the
      epoxyketone 21, which undergoes spontaneous pyran and hemiacetal ring formation
      to 1 on deprotection with DDQ.

PMID- 14664385
TI  - The synthesis of the anti-malarial natural product polysphorin and analogues
      using polymer-supported reagents and scavengers.
AB  - A general asymmetric route to both enantiomers of polysphorin has been developed.
      The route utilizes polymer-supported reagents, catalysts and scavengers to
      minimise the need for aqueous work-up and chromatography. This includes
      application of a method to scavenge 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
      (DDQ) and a "catch-and-release" procedure to extract the resultant diol following
      Sharpless asymmetric dihydroxylation. A novel enzymatic selective protection and
      investigations of a new asymmetric dihydroxylation using microencapsulated osmium
      tetroxide were also investigated during the course of this study.

PMID- 14664386
TI  - Simplified dynemicin analogues: diastereoselective synthesis and evaluation of
      their activity against plasmid DNA.
AB  - The total synthesis of two diastereoisomeric simplified dynemicin analogues is
      reported. The key steps involved are: the regio- and diastereoselective
      functionalisation of an appropriate racemic quinoline precursor and the ring
      closure to give the 10-membered enediyne moiety through a Pd(0)-catalysed Stille
      reaction. After the successful conversion of one of these derivatives into a
      compound more readily activable under nearly physiological conditions, the
      activity against plasmid DNA was evaluated.

PMID- 14664387
TI  - Synthesis of sparteine-like chiral diamines and evaluation in the
      enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine.
AB  - Three chiral diamines were synthesised and evaluated as sparteine surrogates in
      the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis
      and attempted resolution of sparteine-like diamines [(1S*,2R*,8R*)-10-methyl-6,10
      diazatricyclo[6.3.1.0(2,6)]dodecane and (1S*,2R*,9R*)-11-methyl-7,11
      diazatricyclo[7.3.1.0(2,7)]tridecane] (via inclusion complex formation) are
      reported. Unfortunately, it was only possible to resolve the
      diazatricyclo[7.3.1.0(2,7)]tridecane compound. An alternative route to (1R,2S,9S)
      11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane starting from the natural
      product, (-)-cytisine, is described. This simple three-step route furnished gram
      quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate
      in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2
      a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic
      diamines described in this paper to be unequivocally established. Two other
      diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were
      prepared using standard methods. These diamines lacked the bispidine framework of
      (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was
      concluded that, for the asymmetric lithiation substitution of N-Boc pyrrolidine,
      a rigid bispidine framework and only three of the four rings of (-)-sparteine are
      needed for high enantioselectivity. Furthermore, it is shown that diamine
      (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane is the first
      successful (+)-sparteine surrogate.

PMID- 14664388
TI  - Stereocontrol of 1,5-related stereocentres using an intermediate silyl group--the
      diastereoselectivity of nucleophilic attack on a double bond adjacent to a
      stereogenic centre carrying a silyl group.
AB  - R-5-Methylcyclohex-2-enone 1 reacts successively with the
      phenyldimethylsilylzincate reagent and acetaldehyde to give with regiocontrol the
      aldols 7, dehydration of which creates the E-exocyclic double bond of the
      alpha,beta-unsaturated ketone 2. Conjugate addition of the ethylcuprate reagent
      to this compound takes place with high (96:4) selectivity in favour of the R
      stereoisomer 12, hydrolysis of which gives (2R,3R,5S,2'R)-2-(but-2'-yl)-3
      dimethyl(phenyl)silyl-5-methylcyclohexanone 3. The oxime acetate of this ketone
      undergoes fragmentation in the presence of trimethylsilyl
      trifluoromethanesulfonate to give 3R,7R,5E-3,7-dimethylnon-5-enonitrile 4, in
      which an open-chain 1,5-stereochemical relationship is set up with a high level
      of stereocontrol. A similar sequence adding 4-methylpentylcuprate to the enone 2,
      and fragmentation gives 3R,7R,5E-3,7,11-trimethyldodec-5-enonitrile 20. Reduction
      and hydrogenation of this nitrile gives 3R,7R-3,7,11-trimethyldodecanal 22, which
      can be converted into phytol 25. The ketoaldehyde 29 reacts with samarium iodide
      to give only the alcohol 30, in which the radical anion has attacked from the top
      surface just like the cuprate reagents in their reactions with the ketone 2.

PMID- 14664389
TI  - The Ireland-Claisen rearrangement as a probe for the diastereoselectivity of
      nucleophilic attack on a double bond adjacent to a stereogenic centre carrying a
      silyl group.
AB  - The E- and Z-silyl enol ethers 4 derived from allyl 3-R-3
      dimethyl(phenyl)silylpropanoate (R = Me, Pr(i) and Ph) and the Z-silyl enol
      ethers 7 derived from 4-R-4-dimethyl(phenyl)silylbut-2-enyl acetate (R = Me and
      Pr(i)) undergo Ireland-Claisen rearrangements largely in the same stereochemical
      sense, with C-C bond formation taking place anti to the silyl group in the
      conformations 22, 23 and 24 in which the hydrogen atom on the stereogenic centre
      is inside, more or less eclipsing the double bond. The E-silyl enol ether E-7a
      derived from 4-methyl-4-dimethyl(phenyl)silylbut-2-enyl acetate shows low
      diastereoselectivity in the alternative sense, probably because C-C bond
      formation takes place anti to the silyl group in the conformation 26 with the
      methyl group inside, but the silyl enol ether E-7b derived from 4-isopropyl-4
      dimethyl(phenyl)silylbut-2-enyl acetate shows low diastereoselectivity in the
      normal sense. The E- and Z-silyl enol ethers 33 derived from cis-crotyl 3-phenyl
      3-dimethyl(phenyl)silylpropanoate and the E-silyl enol ether 39 derived from
      trans-crotyl 3-phenyl-3-dimethyl(phenyl)silylpropanoate undergo Ireland-Claisen
      rearrangements largely in the same stereochemical sense as their allyl
      counterparts, but with moderately high levels of diastereocontrol in setting up
      the third stereogenic centre following from chair-like transition structures.

PMID- 14664390
TI  - Diastereocontrol in open-chain nucleophilic attack on a double bond adjacent to a
      stereogenic centre carrying a silyl group.
AB  - The bis[dimethyl(phenyl)silyl]cuprate reagent introduces a silyl group to the
      beta-position of three alpha,beta-unsaturated esters: methyl Z-4
      dimethyl(phenyl)silylpent-2-enoate 11, and methyl Z- and E-(1'
      dimethylphenylsilylbenzyl)but-2-enoates 14 and 15, diastereoselectively in the
      unexpected sense, syn to the silyl group in the conformation in which the
      hydrogen atom is 'inside'. The selectivity is low (58:42) in the first case 11,
      where the nucleophilic attack is adjacent to the stereogenic centre carrying the
      silyl group, and moderate (72:28) for both Z- and E-alpha,beta-unsaturated esters
      14 and 15, where the nucleophilic attack is at the other end of the double bond
      from the stereogenic centre. It is conceivable that nucleophilic attack actually
      takes place in a conformation in which the donor substituent, the silicon-carbon
      bond, is out of conjugation with the double bond.

PMID- 14664391
TI  - A new synthesis of pyrroles by the condensation of cyclopropenes and nitriles
      mediated by gallium(III) and indium(III) salts.
AB  - Gallium(III) and indium(III) halides were found to mediate the condensation of
      cyclopropenes and nitriles to give pyrrole derivatives in moderate yields. When
      excess nitrile was present, diazepine was also formed.

PMID- 14664392
TI  - Reaction of 5-halo-1,2,3-thiadiazoles with aliphatic diamines. Synthesis and
      intramolecular cyclization of bis(1,2,3-triazolyl-1,2,3-thiadiazolyl)sulfides.
AB  - Bis[1,2,3]triazolo[1,5-f:5',1'-b][1,3,6]thiadiazepine and [1,5-g:5',1'
      b][1,3,7]thiadiazocine ring systems have been synthesized from 5-halo-1,2,3
      thiadiazoles and aliphatic diamines. We have found that the last step of the
      process is the cyclization of initially formed bis(1,2,3-triazolyl-1,2,3
      thiadiazolyl)sulfides. The structures of the intermediates and products were
      supported by different NMR spectroscopic methods (1H coupled 13C NMR, 2D HETCOR,
      HMBC and 1D INADEQUATE experiments) and mass spectrometry. Differences in the
      reaction pathway for aliphatic and less nucleophilic aromatic diamines were
      determined.

PMID- 14664393
TI  - C-glycosylmethylene carbenes: synthesis of anhydro-aldose tosylhydrazones as
      precursors; generation and a new synthetic route to exo-glycals.
AB  - Acylated anhydro-aldononitriles (glycosyl cyanides) were transformed into anhydro
      aldose tosylhydrazones by Raney-nickel reduction in the presence of
      tosylhydrazine in a one-pot reaction. The configuration of the C=N double bond in
      these hydrazones was E as proven by 15N-1H coupling constants as well as X-ray
      crystallography. Thermolysis in refluxing 1,4-dioxane of the sodium salts of the
      tosylhydrazones obtained by sodium hydride (generally 10 eq.) resulted in the
      formation of anhydro-1-deoxy-ald-1-enitols (exo-glycals). "Dimeric" N
      glycosylmethyl anhydro-aldose tosylhydrazones could also be isolated when the use
      of less base caused incomplete deprotonation of the starting compounds. This two
      step procedure constitutes a novel, reasonably short synthetic pathway to
      acylated exo-glycals from the readily available glycosyl cyanides.

PMID- 14664394
TI  - Intramolecular radical additions to pyridines.
AB  - Intramolecular 6-exolendo-trig and 5-exo-trig cyclisations of aryl radical
      intermediates to the alpha-, beta- and gamma-carbons of pyridine have been shown
      to be facile processes at neutral pH. The tether conjoining the radical donor to
      the pyridine plays an important role in determining the outcome of the reaction.
      When a Z-alkene is used as a tether, ortho-cyclisation proceeds in good yield. A
      more complex course is followed when a saturated two carbon tether is employed,
      leading to products derived from hydrogen atom abstraction, ipso-cyclisation and
      ortho-cyclisation pathways. All attempts to effect 5-exolendo-trig cyclisations
      failed. Tributyltin hydride, tris(trimethylsilyl)silane,
      tris(trimethylsilyl)germane and, in part, samarium(II) iodide can each be
      employed as mediators of the reaction.

PMID- 14664395
TI  - Structure, modelling and dynamic behaviour of aza- and azaoxamacrocyclic ligands
      derived from (R,R)-1,2-diaminocyclohexane.
AB  - Investigations into the conformational behaviour of macrocyclic ligands 5 and 6
      derived from (R,R)-1,2-diaminocyclohexane have been undertaken using molecular
      modelling, single crystal X-ray diffraction and variable temperature 1H NMR
      spectroscopy. These have revealed that the lowest energy conformers in both cases
      do not possess the expected C2-element of symmetry, which can only be accessed at
      higher temperatures. Instead both molecules exist as C1-conformers at room
      temperature and in the solid state. In solution a range of dynamic exchange
      processes is observed which result, in part from the inherent strain in these
      fused bicyclic systems. An unexpected but characteristic feature of the C1
      symmetric conformers is highlighted by the presence of a signal at unexpectedly
      low field in their 1H NMR spectra due to the interaction of two of the sulfonyl
      oxygen atoms with one of the bridgehead hydrogen atoms.

PMID- 14664396
TI  - The charge delocalised beta,beta-carotene dication--preparation, structure
      elucidation by NMR and reactions with nucleophiles.
AB  - The reaction between beta,beta-carotene and BF3-etherates has been investigated,
      leading to structural elucidation of the blue product, formed in appropriate
      organic solvents, as a symmetrical charge delocalised dication (lambda(max) 985
      nm at room temperature in CHCl3) with considerable stability. The reaction,
      monitored by EPR studies at -25 degrees C, occurred via free radical
      intermediates. A C40H56BF3 intermediate was captured by EIMS. The detailed
      structure of the dication was established by COSY, HSQC, HMBC and 1D and 2D ROESY
      NMR techniques (600 MHz, CDCl3, -20 degrees C) leading to complete assignments of
      1H and 13C chemical shifts and 3J(H,H) coupling constants. The effects of the two
      delocalised charges on chemical shift (charge distribution) and bond distance
      (3J(H,H)) were considered. The results are consistent with charge delocalisation
      mainly in the C-5-C-9 and C-5'-C-9' regions and with bond inversion to retro
      shifted double bonds in the central C-13-C-13' region. A convention for denoting
      the charge delocalisation and bond types is presented. The experimental results
      are discussed relative to previous theoretical calculations of the beta,beta
      carotene dication structure. (All-E) and (15-Z)-beta,beta-carotene provided the
      same dication. The NIR spectra and stability of dications prepared in the same
      manner from the related carotenes 20,20'-dinor-beta,beta-carotene, heptapreno
      beta,beta-carotene and nonapreno-beta,beta-carotene were examined for comparison.
      Reactions of the beta,beta-carotene dication with selected nucleophiles provided
      products including isocryptoxanthin, isocarotene and mutatochrome with H2O as
      nucleophile, and isocryptoxanthin methyl ether, 8-methoxy-7,8-dihydro-beta,beta
      carotene and isocarotene with CH3ONa as nucleophile. The formation of these
      products is rationalised from the structure assigned to the dication.

PMID- 14664397
TI  - Thiol-catalysed radical-chain redox rearrangement reactions of benzylidene
      acetals derived from terpenoid diols.
AB  - The thiol-catalysed radical-chain redox rearrangement of cyclic benzylidene
      acetals derived from 1,2- and 1,3-diols of terpene origin has been investigated
      from both synthetic and mechanistic standpoints. The redox rearrangement was
      carried out either at ca. 70 degrees C (using Bu(t)ON=NOBu(t) as initiator) or at
      ca. 130 degrees C (using Bu(t)OOBu(t) as initiator) in the presence of
      triisopropylsilanethiol or methyl thioglycolate as catalyst; the silanethiol was
      usually more effective. This general reaction affords the benzoate ester of the
      monodeoxygenated diol, unless rearrangement of intermediate carbon-centred
      radicals takes place prior to final trapping by the thiol to give the product, in
      which case structurally rearranged esters are obtained. For the benzylidene
      acetals of 1,2-diols prepared by vicinal cis-dihydroxylation of 2-carene, alpha
      pinene or beta-pinene, intermediate cyclopropylcarbinyl or cyclobutylcarbinyl
      radicals are involved and ring opening of these leads ultimately to unsaturated
      monocyclic benzoates. 1,2-Migration of the benzoate group in the intermediate
      beta-benzoyloxyalkyl radical sometimes also competes with thiol trapping during
      the redox rearrangement of benzylidene acetals derived from 1,2-diols. Redox
      rearrangement of the benzylidene acetal from carane-3,4-diol, obtained by cis
      dihydroxylation of 3-carene, does not involve intermediate cyclopropylcarbinyl
      radicals and leads to benzoate ester in which the bicyclic carane skeleton is
      retained. The inefficient redox rearrangement of the relatively rigid benzylidene
      acetal from exo,exo-norbornane-2,3-diol is attributed to comparatively slow chain
      propagating beta-scission of the intermediate 2-phenyl-1,3-dioxolan-2-yl radical,
      probably caused by the development of adverse angle strain in the transition
      state for this cleavage. Similar angle strain effects are thought to influence
      the regioselectivities of redox rearrangement of bicyclic [4.4.0]benzylidene
      acetals resulting from selected 1,3-diols, themselves prepared by reduction of
      aldol adducts derived from reactions of aldehydes with the kinetic lithium
      enolates obtained from menthone and from isomenthone.

PMID- 14664398
TI  - Kinetic study of the electron-transfer oxidation of the phenolate anion of a
      vitamin E model by molecular oxygen generating superoxide anion in an aprotic
      medium.
AB  - Electron-transfer reduction of molecular oxygen (O2) by the phenolate anion (1-)
      of a vitamin E model, 2,2,5,7,8-pentamethylchroman-6-ol (1H), occurred to produce
      superoxide anion, which could be directly detected by a low-temperature EPR
      measurement. The rate of electron transfer from 1- to O2 was relatively slow,
      since this process is energetically unfavourable. The one-electron oxidation
      potential of 1- determined by cyclic voltammetric measurements is sufficiently
      negative to reduce 2,2-bis(4-tert-octylphenyl)-1-picrylhydrazyl radical (DOPPH*)
      to the corresponding one-electron reduced anion, DOPPH-, suggesting that 1- can
      also act as an efficient radical scavenger.

PMID- 14664399
TI  - Modification of calix[4]arenes with CMPO-functions at the wide rim. Synthesis,
      solution behavior, and separation of actinides from lanthanides.
AB  - Two calix[4]arene tetraethers (Y = C5H11, C14H29) bearing on their wide rim four 
      N(Me)-CO-CH2-P(O)Ph2 residues were synthesized for the first time. Their ability
      to extract lanthanides and actinides from an acidic aqueous phase to organic
      phases (CH2Cl2, NPHE) was studied. In comparison to the corresponding -NH
      analogs, they are less efficient extractants, the selectivity for the light over
      the heavy lanthanides is less pronounced, while there is still an interesting
      selectivity of Am3+ over Eu3+. Stability constants for selected lanthanide salts
      were determined also in homogenous phase (methanol, acetonitrile) but do not
      account for the different extraction results. The complexation of Gd3+ was also
      followed by relaxivity (NM RD) measurements, which suggest an even stronger
      aggregation for the N-methyl compound while the 1:1 complex is reached for a
      smaller ratio [L]/[Gd3+] compared to the NH analog. The formation of aggregates
      is also supported by dynamic light scattering measurements. A single crystal X
      ray structure of the pentyl ether reveals a C2-symmetrical pinched cone
      conformation for the free ligand.

PMID- 14664400
TI  - Translational isomerism and dynamics in multi-hydroquinone derived porphyrin [2]-
      and [3]-catenanes.
AB  - A series of porphyrins strapped with polyether chains containing two or three 1,4
      dioxybenzene units has been synthesised with a view to the production of
      porphyrin-containing [2] and [3]catenanes, where the porphyrin is strapped
      between ortho-positions of 5,15-(meso)-diaryl groups, and is interlinked with the
      bipyridinium macrocycle cyclobis(paraquat-4,4'-biphenylene). The porphyrins were
      isolated as mixtures of atropisomers, where the linking strap spans across the
      face of the porphyrin (alpha,alpha-isomer), or 'twisted' around its side
      (alpha,beta-isomer). Their structures were determined by detailed 1H NMR
      spectroscopy. The bis-1,4-dioxybenzene-strapped derivatives were shown to undergo
      atropisomerisation on heating, to produce an equilibrium mixture. Catenation
      under high pressure conditions of the mixture, or of the individual isomers,
      produced only a single catenane, that of the alpha,alpha-isomer. Its structure
      was determined by mass spectral and dynamic NMR measurements. Rates were
      determined for: (i) translational motion or 'shuttling' between 1,4
      dioxybenzenes; (ii) 'rotation' of the macrocycle around the 1,4-dioxybenzene
      axis; and (iii) 'rocking' of the 1,4-dioxybenzene within the macrocycle. The
      atropisomers of the strapped derivatives containing three 1,4-dioxybenzene units
      were also separated, and subjected to catenation. Both [2]- and [3]catenanes were
      isolated, and were shown to be stable to further atropisomerisation. Their
      solution structures were probed in detail by dynamic 1H NMR measurements. The
      rates for shuttling and rotation were obtained in certain cases, although the
      complexity of the spectra of the [3]catenanes prevented a more detailed
      investigation.

PMID- 14664401
TI  - Water soluble sapphyrins: potential fluorescent phosphate anion sensors.
AB  - As part of an ongoing effort to study the anion binding properties of sapphyrins
      in various media, a number of previously reported water solubilized sapphyrins
      were studied in methanol and in buffered, neutral aqueous solutions and found to
      undergo self-aggregation under these solution phase conditions. The nature of the
      species produced as the result of self-aggregation and the processes leading to
      their formation were studied via UV-vis absorbance and fluorescence spectroscopy.
      In previous work (V. Kral, H. Furuta, K. Shreder, V. Lynch, and J. L. Sessler, J.
      Am. Chem. Soc. 1996, 118 1595-1607) it was found that the addition of phosphate
      type anions to water soluble sapphyrins at pH 6.1 gives rise to visible
      spectroscopic changes consistent with the binding to the aggregated form and the
      concurrent formation of an anion-bound dimer with effective equilibrium constants
      on the order of 100-300 M(-1). In this study we show that at high phosphate-to
      sapphyrin ratios in neutral, buffered aqueous solutions further deaggregation
      occurs to produce an anion-bound monomeric form. This highly fluorescent species
      is formed with effective equilibrium constants on the order of 6-19 M(-1) leading
      to considerations that sapphyrins could function as fluorescent phosphate anion
      sensors. In an effort to modulate the deaggregation properties, several new
      sapphyrin derivatives bearing two meso aryl substituents were prepared and
      studied. The aggregation properties of these latter systems were analyzed in
      methanol and, in the case of one water solublized system, in neutral aqueous
      media. In analogy to what was observed for the beta-alkyl substituted sapphyrins,
      H-type aggregates were seen for the water solubilized meso-substituted system in
      aqueous media. However, in contrast to the H-type dimers seen in the case of the
      meso-free systems in methanol, J-type dimers were observed in the case of the
      sapphyrins bearing two meso substituents in this solvent. The effective
      dimerization constants of several of the meso-diaryl sapphyrins were determined
      in methanol as were their pKa values in aqueous media. The solid state structure
      of the bis HBr salt of one of the meso-diaryl sapphyrins, specifically 10,15
      bis(3,5-di-tert-butylphenyl)-3,22-diethyl-2,23-dimethylsapphyrin, was also
      determined and found to show elements in common with those of previously reported
      sapphyrin derivatives. In particular, the two counter anions were found to be
      hydrogen bound above and below the diprotonated sapphyrin plane.

PMID- 14664402
TI  - L-lysine based gemini organogelators: their organogelation properties and
      thermally stable organogels.
AB  - Novel gemini organogelators based on L-lysine, in which two L-lysine derivatives
      are linked by different alkylene chain lengths through the amide bond, have been
      simply and effectively synthesized, and their organogelation abilities and
      thermal stabilities have been investigated. In a series of L-lysine ethyl ester
      derivatives, the organogelation abilities decreased with increasing alkylene
      spacer length. In particular, bis(N(epsilon)-lauroyl-L-lysine ethyl ester) oxalyl
      amide is a good organogelator that gels most organic solvents such as alcohols,
      cyclic ethers, aromatic solvents and acetonitrile. Various oxalyl amide
      derivatives with different alkyl ester groups such as hexyl, decyl, dodecyl, 2
      ethyl-1-hexyl and 3,5,5-trimethylhexyl also showed good organogelation abilities.
      Furthermore, it was found that the cyclohexane gels formed by some oxalyl amide
      derivatives have a high thermal stability.

PMID- 14664403
TI  - Cytodiagnosis in cervical neoplasia: from the Babes/Papanicolaou smear to the
      actual Bethesda System.
AB  - The detection of cell abnormalities by studying cervico-vaginal smears dates from
      1927. Papanicolaou and Traut are still considered the fathers of this method even
      if two Romanian scientists, A. Babes and C. Daniel first published the technique.
      Cervical cytology since then has become a useful and worldwide used screening
      test for cervical cancer. It cannot be used as a means of ultimate diagnosis as
      it has to be confirmed by a tissue diagnosis. The method has an acceptable
      sensitivity and specificity. In 1988 a new system of cytologic analysis was
      introduced: the Bethesda System. It provides a uniform format and offers a
      standardized lexicon for cervical cytopathology reports. The system was revised
      in 1991 and again in 2001. Recent discoveries about the precursors of cervical
      cancer and the availability of new cytologic testing methods now make it possible
      to incorporate new approaches into managing women with cytologic abnormalities.

PMID- 14664404
TI  - Actual trends in screening, diagnosis and prognosis of endometrial cancer.
AB  - Endometrial cancer is today the first ranking malignancy of the female genital
      tract in civilized countries. We stress the importance of screening and an early
      accurate diagnosis with personalized therapy. Personalized therapy is
      particularly important considering that there are two main forms of these
      neoplasms: the endometrioid form, hormonodependent and with a good prognosis, and
      a serous autonomous form, which has a poor evolution. Studying the cases in the
      Ist Clinic of Gynecology, Timisoara, we analyzed the incidence of these forms,
      their particularities and diagnostic possibilities.

PMID- 14664405
TI  - Uterine cervical elongation and prolapse during pregnancy: an old unsolved
      problem.
AB  - Prolapse with elongation of the cervix is a rare complication of pregnancy.
      Prolapse that existed before onset of pregnancy will usually resolve
      spontaneously by the end of the second trimester, without further complications.
      A pessary can be used to protect the cervix. Prolapse that develops during
      pregnancy is usually first noted in the third trimester, and management consists
      of bed rest in a slight Trendelenburg position. In these cases, pessaries will
      probably not remain in place or prevent preterm labor. Patient discomfort,
      urinary tract infection, acute urinary retention, premature labor, and prenatal
      loss are still major complications, and prolapse usually persists or recurs after
      labor. Treatment depends on the severity of the condition and the patient's
      preference.

PMID- 14664406
TI  - Could the theory of chaos contribute to the interpretation of pathogenesis of
      polycystic ovary syndrome?
AB  - Polycystic ovary syndrome (PCOS) is a syndrome involving defects in primary
      cellular control mechanisms that result in the expression of chronic anovulation
      and hyperandrogenism. In this syndrome the relation between the various
      parameters is of particular interest. These relations constitute the cornerstone
      of the pathogenesis of PCOS. The fact that the pathogenesis of the PCOS has not
      yet been clarified, despite the plethora of relative information, may be the
      result of a general way of thinking in the interpretation of several scientific
      data, and especially those that refer to biochemical phenomena. The use of the
      various models of the theory of chaos, that permits a concrete approach for the
      interpretation of data, may constitute an optional procedure for the future
      understanding of the association of different parameters and their disturbances
      in the pathogenesis of PCOS.

PMID- 14664407
TI  - Three-dimensional sonography and hysterosalpingosonography in the diagnosis of
      uterine anomalies.
AB  - Uterine anomalies implicated in female subfertility, implantation failure and
      miscarriages can often be detected often by two-dimensional transvaginal (2D TV)
      ultrasound scanning. When used as a screening test TV ultrasound has provided
      sensitivity rates of up to 100% about uterine anomalies. Improved depiction has
      been achieved with the development of hysterosalpingosonography (HSSG). The
      anechoic interface provided by the saline solution allows the examiner to
      determine whether an abnormality is intracavitary, endometrial, or submucosal.
      The aim of this study was to evaluate the role of 2D TV contrast sonography and
      3D TV ultrasound in the diagnosis of congenital uterine anomalies in comparison
      with their appearance of hysterosalpingosonography findings.

PMID- 14664408
TI  - Slow rising serial chorionic gonadotropins predict poor pregnancy outcome despite
      sonographic viability.
AB  - PURPOSE: To determine the prognosis of women with slow rising beta-hCG levels
      when viability is detected by ultrasound. METHODS: Serum beta-hCG levels were
      obtained every two to three days in the early first trimester. Doubling-time (DT)
      of beta-hCG levels was defined as DT exceeding 3.2 days. Sonography was performed
      at eight weeks and then after 12 weeks. RESULTS: There were 158 consecutive
      pregnancies evaluated and 111 (70%) had normal rising beta-hCG levels, viable
      ultrasound at eight weeks, and viable pregnancies after 12 weeks. There were 22
      pregnancies with slow rising beta-hCG levels (13.9%) with 16 (72.7%) showing
      viability at eight weeks but not after the first trimester. A sac-crown rump
      length discrepancy with a sac smaller than normal was found in 11 of these 16
      (68.7%) women. CONCLUSIONS: Patients with slow rising beta-hCG levels should not
      be given an optimistic prognosis even if viability is demonstrated at eight
      weeks.

PMID- 14664409
TI  - Effect of short follicular phase with follicular maturity on conception outcome.
AB  - PURPOSE: To determine if a short follicular phase despite attaining a mature
      follicle is associated with a lower pregnancy rate. Furthermore the study would
      determine if delaying the maturation of the follicle by the use of ethinyl
      estradiol could improve the pregnancy rate. METHODS: The clinical and viable
      pregnancy rates of 32 infertile patients were matched to 32 similar controls who
      ovulated at or past day 11. After 2-3 cycles of demonstrating ovulation before
      day 11 some patients were treated with ethinyl E2, 20 mcg daily, from day 2 of
      the cycle until ovulation. RESULTS: Clinical and viable pregnancy rates for the
      normal ovulators (84.4%, 59.3%) were significantly higher than the rates for
      early ovulators (21.8%, 9.3%). However, the pregnancy rates were 83.3% and 66.7%
      for the subset of early ovulators who were made to ovulate later by ethinyl E2.
      CONCLUSIONS: The short follicular phase per se reduces fecundity.

PMID- 14664410
TI  - Effect of transferring frozen-thawed embryos resulting from fertilization of
      immature oocytes matured one day in culture prior to intracytoplasmic sperm
      injection (ICSI) on implantation rates.
AB  - PURPOSE: To evaluate whether it is efficacious to allow immature (metaphase I or
      germinal vesicle stage) oocytes to incubate one more day and then perform ICSI.
      METHOD: A retrospective study of frozen embryo transfers (ET) of deselected
      frozen embryos was performed to see if inclusion of a higher percentage of
      embryos derived from in vitro maturation of oocytes resulted in lower
      implantation rates. RESULTS: The implantation rate following transfer of frozen
      thawed embryos, where embryos derived from immature oocytes constituted < or =
      40% of the embryos (group 1) was similar to group 2 with > 40% (11.3% vs 9.8%).
      However, group 1 had a 10.2% implantation rate for viable (past first trimester)
      sacs vs only 4.3% for group 2. CONCLUSIONS: Pregnancies from transfer of frozen
      thawed embryos derived from in vitro cultured immature oocytes are as likely to
      implant as the other deselected frozen-thawed embryos.

PMID- 14664411
TI  - Efficacy of sharing oocytes from compensated donors between two recipients.
AB  - PURPOSE: To see if sharing of donated oocytes from a compensated donor lowers
      outcome following embryo transfer compared to recipients keeping all oocytes.
      METHOD: Retrospective review. Recipients have the option of keeping all oocytes
      or sharing to reduce costs. RESULTS: There were equal clinical, and
      ongoing/delivered pregnancy rates and implantation rates in the two groups. There
      were almost twice as many frozen embryos available to recipients who did not
      share for potential future use. CONCLUSIONS: Sharing of oocytes between two
      recipients reduces the financial burden for the recipient without affecting
      efficacy. Such a policy would make more oocytes available to recipients and thus
      shorten the long waiting times.

PMID- 14664412
TI  - An evaluation of the efficacy of using oocyte donors aged 36-39.
AB  - PURPOSE: To determine if oocyte donors aged 36-39 can provide adequate pregnancy
      rates for recipients. METHODS: Retrospective analysis of clinical,
      ongoing/delivered pregnancy and implantation rates for a group of recipients
      receiving oocytes from a pilot group of older donors. RESULTS: Comparable
      pregnancy and implantation rates were found in recipients transferring embryos
      derived from donors aged 36-39 as recipients using oocytes from donors < or = 35.
      CONCLUSIONS: The demonstration of adequate outcome following embryo transfer from
      embryos derived from fertilization of oocytes from donors aged 36-39 should
      expand the pool of donor oocytes and reduce the long waiting times for
      recipients.

PMID- 14664413
TI  - The immediate effect of natural plant extract, Angelica sinensis and Matricaria
      chamomilla (Climex) for the treatment of hot flushes during menopause. A
      preliminary report.
AB  - OBJECTIVE: To assess the efficiency of a medicinal herb extract preparation
      (Climex) for the treatment of menopausal symptoms. METHOD: In this placebo
      controlled experiment on 55 postmenopausal women who complained of hot flushes
      and refused hormonal therapy. The women were randomly divided into two groups,
      one to receive Climex (5 chewable tablets daily between meals) and the other
      group to receive a placebo; both groups would take the tablets for 12 weeks. The
      women were asked to complete a daily structured (Kupperman) questionnaire
      assessing the frequency and intensity of menopausal symptoms, starting one week
      prior to treatment to the completion of the study. All women underwent hormone
      profile measurements and transvaginal ultrasonography evaluation before and after
      treatment. RESULTS: There was a significant difference between the study group
      and the control group in the decrease in number and intensity of hot flushes from
      baseline to completion of treatment (90-96% vs 15-25%, p < 0.001). In the study
      group, a response was already noted during the first month of treatment (68% +/-
      2% reduction of hot flushes during the day and 74% +/- 4% during the night).
      There was also a marked alleviation of sleep disturbances and fatigue.
      CONCLUSIONS: Treatment with Climex seems to be effective for menopausal symptoms
      without apparent major adverse effects. This hormone-free preparation may be used
      as an important modality for menopausal women with contraindications for hormone
      replacement therapy.

PMID- 14664414
TI  - Serum leptin levels in normal-weight and overweight women with polycystic ovary
      syndrome.
AB  - The aim of this study was to evaluate serum leptin levels in women with
      polycystic ovary syndrome (PCOS) and in controls with normal or abnormal body
      mass index (BMI), since the literature data are contradictory. The study
      population comprised 34 women with PCOS and 30 regularly cycling women, with
      normal or abnormal BMI. PCOS was defined by clinical, ultrasonographic, and
      hormonal findings. The women were divided into four groups according to the
      diagnosis of PCOS and their BMI values. In all women serum levels of FSH, LH,
      prolactin, testosterone, androstenedione, DHEA-S, 17alpha-OH progesterone, SHBG,
      insulin, glucose and leptin were determined. It was found that: (a) there was a
      significant interaction between BMI and PCOS in increasing serum leptin levels;
      (b) the dominant factor for serum leptin levels in women of all Groups was BMI,
      followed by insulin; (c) once we corrected for BMI, it was found that there was a
      significant correlation between serum leptin levels and insulin values, as well
      as between serum leptin levels and testosterone concentrations; and (d) the
      QUICKI IR formula presented the most significant correlation with serum leptin
      levels than the other measures of insulin sensitivity. Our results showed that
      serum leptin levels in a subgroup of overweight women with PCOS and insulin
      resistance were higher than those expected for their BMI, and therefore leptin
      might interfere in the pathogenesis of this syndrome.

PMID- 14664415
TI  - Fetomaternal Doppler sonography nomograms.
AB  - PURPOSE: To constitute Doppler flow velocity nomograms for use in obstetric
      clinics and to analyse the technical infrastructure of constructing Doppler
      sonography nomograms for clinical use. METHODS: On a cross-sectional study plan
      basis 602 flow results of 370 pregnant women were used. Pregnancy gestational
      ages were confirmed with an early sonogram prior to the 14th gestational week.
      Patients in whom primary section for placental insufficiency had to be done, who
      had pathological fetal heart rate monitoring, signs of intrauterine asphyxia,
      multiple pregnancy or a fetal anomaly were excluded. Every two gestational weeks
      patients were grouped and for these groups the 5th, 10th, 50th, 90th and 95th
      percentiles were calculated to represent the umbilical artery, fetal aorta,
      middle cerebral artery (MCA) and uterine artery S/D ratio, resistence index (RI)
      and pulsatility index (PI) Doppler flow velocity nomograms. RESULTS: In normal
      pregnancies, after the 22nd-24th gestational week, the uteroplacental flow
      velocities were constant, but at the fetal vessels there were changes in velocity
      waveforms after this period. With advancing gestation in the third trimester,
      umbilical artery and middle cerebral artery impedance was lower and the
      resistance in the descending fetal aorta remained nearly constant. CONCLUSION:
      With growing gestational age the Doppler velocity forms change. In fact because
      of this, for Doppler velocity studies and to differentiate between normal and
      abnormal pregnancy status, nomograms adapted to gestational age should be used.
      For practical use in different obstetrics clinics, we are presenting our Doppler
      velocity norm-curves.

PMID- 14664416
TI  - Preoperative evaluation of ovarian masses: ultrasound and biochemical screening.
AB  - OBJECTIVE: The preoperative study of an ovarian mass, with a negative dosage of
      plasmatic BhCG, mainly has the purpose of discriminating between a benign
      neoplastic mass and a malignant mass. The aim of our work was to evaluate the
      validity of preoperative screening including a pelvic ultrasound examination and
      the dosage of some plasmatic tumor markers. METHODS: This is a retrospective
      study conducted on 78 patients who were referred to the III Division of the
      Department of Gynaecological Sciences, Perinatology and Puericulture of Rome
      University "La Sapienza" from January 1st 2001 to December 31st 2001 with a
      diagnosis of ovarian tumefaction whose origin was still to be determined. These
      patients underwent both a transabdominal and transvaginal ultrasound scan and
      biochemical examination of serum levels of Ca-125, Ca 19-9 and CEA. Subsequently
      these patients underwent surgery or medical therapy according to the suspected
      diagnosis. We then compared our suspected diagnosis with the precise histological
      diagnosis. Finally, following this comparison, we judged the validity of the
      proposed screening. RESULTS: Ultrasound examination is on its own an excellent
      method for preoperative screening in cases of adnexal tumefactions. However, its
      association with plasmatic dosages of Ca 125, Ca 19-9 and CEA improves the
      validity of the screening. CONCLUSION: The use of pelvic scanning, both
      transabdominal and transvaginal, associated with plasmatic dosages of Ca 125, Ca
      19-9 and CEA, represents an excellent method of preoperative screening for the
      evaluation of benign or malignant ovarian tumefactions and for directing the
      surgeon towards the best therapy.

PMID- 14664417
TI  - Clinical and urodynamic evaluation of women with detrusor instability before and
      after functional pelvic floor electrostimulation.
AB  - Detrusor instability is the second most frequent cause of female urinary
      incontinence. There are many therapeutic options, including non-invasive and
      surgical procedures. In this study, we evaluated the effects of pelvic floor
      vaginal electrostimulation using equipment designed in our institution, over
      three consecutive months, for treatment of 29 women with detrusor instability.
      After treatment 22 patients (76%) considered themselves cured or symptomatically
      improved; seven patients (24%) had no change in symptoms after therapy. There was
      objective cure and improvement in ten (34.5%) and in eight (27.5%) patients,
      respectively, and the urodynamic parameters did not change in 11 patients (38%).
      Electrical stimulation resulted in a gradual decrease in the number of urinary
      leakage episodes and increase in maximum cystometric capacity in first desire to
      void and in urinary volume.

PMID- 14664418
TI  - Accuracy of office hysteroscopy in the diagnosis of endometrial hyperplasia.
AB  - In the last decade the advantages of office hysteroscopy performed without
      cervical dilatation and/or anaesthesia were fully demonstrated. Many authors
      consider office hysteroscopy the gold standard diagnostic method in the diagnosis
      of intrauterine pathology, with high accuracy and compliance. The best
      sensitivity and specificity are reached in the diagnosis of focal lesions as
      submucous myomas and polyps but controversy still persists regarding
      hysteroscopic accuracy in the definition of endometrial hyperplasia. The aim of
      this prospective study was to evaluate the efficacy of outpatient hysteroscopy in
      the diagnosis of endometrial hyperplasia and to compare hysteroscopic findings
      with histology. From April 2000 to May 2002, 145 diagnostic office hysteroscopies
      were performed at the Euganea Medica clinic. Sensitivity in the detection of
      endometrial hyperplasia was 89.36%, specificity 91.96%, positive predictive value
      (PPV) 82.36% while negative predictive value (NPV) reached 95.37%. Uniformity of
      histology associated with outpatient mini-invasivity and high compliance favour
      office hysteroscopy and represent important elements in its diffusion as a first
      level diagnostic method even in the diagnosis of hyperplasia.

PMID- 14664419
TI  - Father-to-son sperm donation. A report of three cases.
AB  - Sperm donation is a common practice in assisted reproduction. In cases of
      azoospermia and negative results of testicular sperm extraction, it appears as
      the only solution. Sperm donation entails a complete genetic dissociation between
      husband and offspring, which brings psychological stress for the couple arising
      from ethical and existential dilemmas. Faced with such dilemmas, some couples
      prefer father-to-son donation as an alternative solution. Here, three cases of
      non-obstructive azoospermia are presented where intracytoplasmic sperm injection
      was performed with father-to-son sperm donation.

PMID- 14664420
TI  - Action of 25 microg 17beta-oestradiol vaginal tablets in the treatment of vaginal
      atrophy in Greek postmenopausal women; clinical study.
AB  - PURPOSE: To evaluate the clinical efficacy and safety of intravaginal application
      of 25 microg micronized oestradiol in postmenopausal women from the Greek
      population suffering from symptoms related to vaginal atrophy. MATERIALS AND
      METHODS: 91 women suffering from vaginal dryness, vaginal itching and dyspareunea
      were treated with 25 microg 17beta-oestradiol vaginal tablets. The duration of
      treatment was 12 weeks. During the first two weeks the women inserted one vaginal
      tablet intravaginally once daily. Thereafter, the women inserted one tablet twice
      per week with at least a 3-day interval between treatments to maintain
      therapeutic response for ten weeks. Efficacy was evaluated by the relief of
      vaginal symptoms and safety by the concentrations of serum oestradiol (E2) and
      follicular-stimulating hormone (FSH). Pretreatment and post-treatment findings
      were compared and each patient served as her own control. RESULTS: The rates of
      symptoms of vaginal dryness, vaginal itching and dyspareunea showed statistically
      significant differences over the course of the trial (Cochran Q test, p < 0.001).
      No one complained of vaginal dryness and vaginal itching after four and six weeks
      of treatment respectively, while in one patient the sensation of dyspareunea
      remained constant after the fourth week of treatment. Despite the statistically
      significant increase in blood oestradiol levels in relation to baseline values
      (ANOVA model of repeated measures, p < 0.001), these levels were within the
      normal range for postmenopausal women. Also, serum FSH levels were statistically
      significantly reduced from 47.4 mIU/ml at entry into the study to 45.5 mIU/ml
      after two weeks of treatment (dependent samples t-test, p < 0.003), but were
      clearly within the postmenopausal range. CONCLUSIONS: The twice-weekly local
      single treatment with vaginal tablets containing 25 microg of 17beta-oestradiol
      was effective and safe for the relief of symptoms related to atrophic vaginitis
      in postmenopausal women from the Greek population.

PMID- 14664421
TI  - Recombinant human erythropoietin in mildly anemic women before total
      hysterectomy.
AB  - The purpose of this study was to investigate the efficacy of preoperative
      recombinant human erythropoietin (rHuEPO) treatment in a group of mildly anemic
      women. METHODS: This randomized controlled study included 50 healthy, mildly
      anemic women who underwent total hysterectomy for leiomyomas. The study group
      (Group A) included 23 women who received rHuEPO 600 U/kg once weekly for three
      weeks, plus iron supplementation. The control group (Group B) included 27 women
      who received only iron supplementation. Blood samples were obtained on days -14, 
      7, 0, +3, +7 and +14. RESULTS: An increase in preoperative mean hemoglobin
      concentration was noted in both groups; however, the increase was significantly
      higher in Group A throughout the study period. Mean reticulocyte count was also
      significantly higher in this group, whereas mean ferritin level was significantly
      lower. No postoperative transfusion was needed in Group A, whereas five women
      were transfused in Group B. CONCLUSION: Rapid and persistent improvement of
      hematologic parameters makes the use of rHuEPO for preoperative treatment of
      mildly anemic women with benign uterine pathology a very interesting approach.

PMID- 14664422
TI  - Preliminary results of orthotopic en bloc uterus and ovary transplantation in the
      laboratory rat.
AB  - A new experimental model of whole uterus and ovary transplantation in the
      laboratory rat was achieved. The main goals of this study were concerned with
      developing and standardizing the microsurgical technique of uterus
      transplantation in rats and observing the particular cellular patterns of acute
      allograft rejection at the level of the transplanted graft. Thirty-five
      orthotopic uterus transplantations were performed. An additional 20 female rats
      were used for dissection training sessions. Recipients were euthanasied at 24
      hours, 48 hours and 72 hours. Immediate postoperative survival was 100%. Patency
      of the microsurgical anastomoses, checked at 24 hours, was 100%. At 72 hours
      thrombosis occurred in all anastomoses. The explanted uterine grafts were fixed
      in formaline and analyzed under light microscopy and specific imunohistochemical
      analysis. The acute allograft rejection has a particular cellular reaction
      pattern, probably due to the unique diversity of the tissues that compose it.
      Inflammatory cells like LTCD8+, LBCD20+ and mastocytes tend to agglomerate in the
      vicinity of nervous and vascular structures, showing no signs of lymphoid tissue
      disposition like in typical acute rejection. Uterus transplantation in rats has
      proven to be a valid experiment that allows us to express hope that by further
      research on transplantation of the uterus gynecologists will be able to introduce
      an adapted technique in the treatment of specific cases of human female
      infertility.

PMID- 14664423
TI  - Peripartum cardiomyopathy: characteristics and outcome in a tertiary care
      hospital.
AB  - PURPOSE OF INVESTIGATION: Peripartum cardiomyopathy (PPCM) has been traditionally
      regarded as a condition with a poor prognosis. We studied the acute and long-term
      outcomes in patients with PPCM in a tertiary care hospital. METHODS: Patients
      with PPCM admitted to our hospital from June 1990 to February 2002 who had
      documented left ventricular (LV) dysfunction by echocardiographic criteria were
      retrospectively reviewed. RESULTS: Out of ten patients who fulfilled the criteria
      for the diagnosis, six (60%) had severe, and four (40%) had moderate LV
      dysfunction at echocardiography. None had evidence of other chronic disease.
      Treatment consisted of fluid restriction, diuresis, and afterload reducers in
      all, and intravenous inotropes in three (30%) of the patients. No patient died
      while in hospital or during follow-up. All patients showed improvement in their
      clinical condition and LV function on follow-up which normalized in seven (70%).
      CONCLUSION: PPCM might carry a relatively good prognosis in patients with absence
      of associated disease conditions.

PMID- 14664424
TI  - Evaluation during early puerperium of the low transverse incision after cesarean
      section through vaginal ultrasonography.
AB  - OBJECTIVE: This study was designed in order to determine the criteria of the
      natural healing of the low transverse cesarean incision through vaginal
      ultrasonography. METHODS: The uterine wound was examined with a vaginal scanner
      (5.5-7 MHz) in 75 asymptomatic patients with a normal postoperative course three
      days after the cesarean section. We compared our findings with those obtained in
      21 patients with a complicated post-cesarean course. RESULTS: The uterine
      incision was identified as an oval, centrally located region between the bladder
      and the uterus. In 18 of the 75 cases, a hypoechoic area with indistinct limits,
      almost rounded and with a diameter of smaller than 1.5 cm in all cases was
      determined in the incision site. Possibly all these cases represented small
      hematomas or serous collections, with no clinical importance. Four of the 21
      symptomatic patients had bladder flap or uterine incision hematomas. These were
      large (> 2 cm in all cases) hypoechoic areas inside or around the transverse
      incision site. CONCLUSION: The low transverse cesarean incision in the uterus can
      be visualized sonographically with a vaginal scanner and normal postoperative
      changes can be recognized.

PMID- 14664425
TI  - Mucinous cystadenoma of the ovary with functioning stroma and virilization in
      pregnancy: a case report and review of the literature.
AB  - Virilization caused by ovarian tumors with functioning stroma during pregnancy is
      extremely rare and has been reported in many ovarian tumors. In mucinous
      cystadenomas with maternal virilization during pregnancy the stromal cells
      responsible for the hormone secretion resemble lutein or Leydig cells and have
      been referred to as luteinized stromal cells. We present a case of a 30-year-old,
      gravida 2, para 1, woman who presented at approximately the 38th week of
      pregnancy with features of virilization. At the same time, a cesarean section was
      performed because of fetal distress and a male weighing 3,030 g without any gross
      abnormalities was delivered. A large tumor of the right ovary was detected and a
      right salpingo-oophorectomy was performed. Histopathologically, the tumor proved
      to be a benign mucinous cystadenoma. Masses typically resembling lutein stromal
      cells or Leydig cells of the testes or ovarian hilus were found in the wall of
      the cyst below the mucinous epithelium. No crystalloids of Reinke were
      identified. The stromal component of the tumor was characterized as functioning
      stroma with luteinized stromal cells. The glandular mucinous epithelium showed
      focal positivity for human chorionic gonadotrophin. The cytoplasm of the
      luteinized stromal cells reacted strongly and diffusely with antiserum for
      vimentin. Also, the cytoplasm of the luteinized stromal cells showed focal
      intense positivity for synaptophysin, and focal mild positivity for human
      chorionic gonadotrophin. Staining results for oestrogen and progesterone
      receptors were negative. In conclusion, we present an unusual case of clinical
      virilization during pregnancy associated with an ovarian mucinous cystadenoma
      with functioning stroma. The virilizing manifestations disappeared after removal
      of the ovarian neoplasm, supporting the perception that the functioning ovarian
      stroma was responsible for the androgen production.

PMID- 14664426
TI  - A voluminous twisted paraovarian cyst in a 74-year-old patient: case report and
      review of the literature.
AB  - Although paraovarian cysts rarely cause symptoms, they may be complicated due to
      massive size, torsion or internal haemorrhage from rupture. Moreover, benign or
      malignant neoplasms may occasionally develop in paraovarian cysts. The risks from
      voluminous ovarian or paraovarian cysts are due to severe cardiovascular,
      pulmonary, and circulatory problems including surgical and postoperative
      complications. We present a case of a 74-year-old patient who suffered from a
      twisted voluminous right paraovarian cyst. Her preoperative respiratory function
      required attention. The patient was treated surgically with good results and she
      showed notable improvement of her respiratory function, postoperatively. The
      maximum diameter of the mass was 26 cm and its total weight was 5,100 g. In
      addition, a simple cyst was found in the left ovary with a maximum diameter of
      9.5 cm and total weight of 300 g. In conclusion, paraovarian cysts, even in
      elderly patients, can reach large sizes requiring awareness of the problems that
      these large masses may cause.

PMID- 14664427
TI  - Triplet pregnancy after oocyte donation in women 46 years of age and older: three
      case reports.
AB  - PURPOSE: Presentation of three triplet pregnancies achieved in women 46 years of
      age and older with the use of donated oocytes. MATERIAL & METHODS: Two healthy
      perimenopausal women 46 and 48 years old and one healthy menopausal woman 48
      years old, requesting fertility options. All of them followed oocyte donation
      programs resulting in triplet pregnancy. Maternal as well as perinatal
      complications, mode of delivery and birth weight are reported. RESULTS: Three
      triplet pregnancies were achieved using donated oocytes. Prenatal diagnosis was
      reassuring. Preterm rupture of membranes, preterm labor and gestational diabetes
      complicated the pregnancies. Cesarean section was the mode of delivery for all
      the cases giving birth to nine healthy neonates weighing between 1,130 and 2,450
      g. No postpartum complications were encountered. CONCLUSIONS: Triplet pregnancies
      achieved with the use of donated oocytes at a very advanced maternal age
      represent high-risk obstetrical cases. Cautious prenatal evaluation of maternal
      health and intensive antenatal surveillance are imperative principles allowing
      the most favorable outcome of these pregnancies.

PMID- 14664428
TI  - Prenatal diagnosis of congenital cystic adenomatoid lung malformation: case
      report and review of the literature.
AB  - Congenital cystic adenomatoid malformation of the fetal lung is an extremely rare
      developmental abnormality characterized by excessive overgrowth of the terminal
      respiratory bronchioles at the expense of the saccular spaces. We present a case
      of a 33-year-old, gravida 2, para 1, woman with congenital cystic adenomatoid
      lung malformation-type II diagnosed by ultrasound at the 20th week of gestation.
      On the right side of the chest an area with a maximum diameter of 18.5 mm and
      with small cystic lesions was recognized. The maximum diameter of the cysts was
      0.5 cm. There were no other fetal abnormalities. The pregnancy was terminated and
      the postmortem examination confirmed the ultrasonographic findings. The cysts had
      the appearance of bronchiolus-like structures and were lined with cuboidal and
      columar epithelium. Distended alveoli were present, while the airways were normal
      in structure. No other congenital anomalies were found. In conclusion, in this
      study we describe the ultrasonographic and pathologic findings of an unusual case
      of congenital cystic adenomatoid malformation of the fetal lung.

PMID- 14664429
TI  - Successful pregnancy in a woman with rare compound heterozygoticity for
      congenital adrenal hyperplasia; case report.
AB  - Pregnancy rates in women with congenital adrenal hyperplasia--even when
      adequately treated--are reported to be low. We hereby describe our recent
      experience with the pregnancy of a patient who had congenital adrenal hyperplasia
      due to a rare combination of P30L/I172N mutations in the CYP21 (21-hydroxylase)
      gene.

PMID- 14664430
TI  - The utility of routine breast ultrasound screening in gynecology.

PMID- 14664431
TI  - Lawsuit seeks stronger protections for primates.

PMID- 14664432
TI  - ACLAM takes stance, addresses threats to medical research.

PMID- 14664433
TI  - Survivors campaign promotes animal research to aid animals.

PMID- 14664434
TI  - A practitioner's academician.

PMID- 14664435
TI  - Two veterinary students learn politics isn't always about money.

PMID- 14664436
TI  - Hill's provides impressive funding for future conventions.

PMID- 14664437
TI  - Opposes AVMA position on gestation stalls, forced molting.

PMID- 14664438
TI  - Applauds WYD article.

PMID- 14664439
TI  - Pet food manufacturer comments on taurine in diets.

PMID- 14664440
TI  - An appeal for better automated medical records.

PMID- 14664441
TI  - What is your diagnosis? Multiple area of lysis of the metaphyses and diaphysis of
      the left femur.

PMID- 14664442
TI  - ECG of the month. Second-degree atrioventricular (AV) block.

PMID- 14664443
TI  - Interactions of substrate availability, exercise performance, and nutrition with
      muscle glycogen metabolism in horses.

PMID- 14664444
TI  - Personal characteristics, knowledge of the veterinary profession, and influences
      on career choice among students in the veterinary school applicant pool.

PMID- 14664445
TI  - Evaluation of the advisory services provided by the Food Animal Residue Avoidance
      Databank.

PMID- 14664446
TI  - Percutaneous ultrasound-guided radiofrequency heat ablation for treatment of
      hyperthyroidism in cats.
AB  - OBJECTIVE: To determine efficacy and safety of percutaneous radiofrequency heat
      ablation for treatment of hyperthyroidism in cats. DESIGN: Prospective study.
      ANIMALS: 9 cats. PROCEDURE: Hyperthyroidism was diagnosed via clinical signs and
      high serum total (TT4) and free thyroxine (fT4) concentrations. One or 2
      hyperfunctional cervical thyroid nodules were detected by use of scintigraphy and
      ultrasonography. If cats had 1 abnormal thyroid lobe, heat ablation was performed
      on that lobe; if cats had 2 abnormal lobes, heat ablation was applied to the
      larger lobe. Overall, heat ablation was performed 14 times in the 9 cats.
      Clinical signs and serum TT4, fT4, and calcium concentrations were monitored
      daily for 2 days after the procedure, weekly for the first month, and then
      monthly. Laryngeal function was evaluated and cervical ultrasonography and
      thyroid scintigraphy were also performed. Monitoring continued for as long as 9
      months after heat ablation if a cat became euthyroid or until an owner chose an
      alternative treatment because of recurrence of hyperthyroidism. RESULTS: Serum
      TT4 and fT4 concentrations transiently decreased after all 14 heat ablation
      procedures (< or = reference range after 10 of 14 treatments) within 2 days after
      the procedure. Cats were euthyroid for 0 to 18 months (mean, 4 months).
      Hyperthyroidism recurred in all cats. Adverse effects included transient Horner's
      syndrome (2 cats) and laryngeal paralysis without clinical signs (1 cat).
      CONCLUSIONS AND CLINICAL RELEVANCE: Percutaneous heat ablation as a treatment for
      hyperthyroidism in cats is effective transiently but not permanently.

PMID- 14664447
TI  - Use of a combination of propofol and fentanyl, alfentanil, or sufentanil for
      total intravenous anesthesia in cats.
AB  - OBJECTIVE: To determine the cardiorespiratory effects of an i.v. infusion of
      propofol alone or in association with fentanyl, alfentanil, or sufentanil in cats
      and, for each combination, the minimal infusion rate of propofol that would
      inhibit a response to noxious stimuli. DESIGN: Randomized crossover study.
      ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized 4 times in random order. After
      i.v. administration of fentanyl, alfentanil, sufentanil, or saline (0.9% NaCl)
      solution, anesthesia was induced with propofol (7 mg/kg 13.2 mg/lb], i.v.) and
      maintained for 90 minutes with a continuous infusion of propofol in conjunction
      with fentanyl (0.1 microg/kg/min [0.045 microg/lb/min]), alfentanil (0.5
      microg/kg/min [0.23 microg/lb/min]), sufentanil (0.01 microg/kg/min [0.004
      microg/lb/min]), or saline solution (0.08 mL/kg/min [0.036 mL/lb/min]). RESULTS:
      Minimal infusion rate of propofol required to prevent a response to a noxious
      stimulus was higher when cats received saline solution. After 70 minutes, minimal
      infusion rate of propofol was significantly higher with fentanyl than with
      sufentanil. Decreases in heart rate, systolic blood pressure, rectal temperature,
      and respiratory rate were detected with all treatments. Oxygen saturation did not
      change significantly, but end-tidal partial pressure of carbon dioxide increased
      with all treatments. There were no significant differences in recovery times or
      sedation and recovery scores among treatments. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that infusion of propofol in combination with
      fentanyl, alfentanil, or sufentanil results in satisfactory anesthesia in cats.

PMID- 14664448
TI  - Use of fetal skeletal mineralization for prediction of parturition date in cats.
AB  - OBJECTIVE: To determine the relationship between parturition date and fetal
      skeletal mineralization detected radiographically in cats. DESIGN: Prospective
      clinical trial. ANIMALS: 31 queens and their 49 pregnancies. PROCEDURE: Seventeen
      pregnant queens were radiographed with a computed radiography system every 2 to 3
      days from 1 week after pregnancy was identified by abdominal palpation until
      parturition. Radiographs were evaluated to determine the first identifiable
      mineralization of 16 bony structures and teeth during each pregnancy. This
      information was used to establish a table of expected parturition dates on the
      basis of fetal mineralization. Single radiographs from an additional 32 pregnant
      cats were evaluated, and predictions of parturition dates were made on the basis
      of the mineralization table. RESULTS: Mineralization was first detected 25 to 29
      days prior to parturition (dpp). Mineralization was determined for the spinal
      column (22 to 27 dpp), skull (21 to 27 dpp), ribs (20 to 25 dpp), scapula (17 to
      24 dpp), humerus (20 to 24 dpp), femur (19 to 23 dpp), radius (15 to 22 dpp),
      tibia (15 to 21 dpp), ulna (5 to 21 dpp), pelvis (8 to 20 dpp), fibula (0 to 17
      dpp), tail (8 to 16 dpp), metacarpals and metatarsals (3 to 14 dpp), phalanges (0
      to 11 dpp), calcaneus (0 to 10 dpp), and teeth (1 to 6 dpp). Date of parturition
      was predictable within 3 days in 75% of cats. CONCLUSIONS AND CLINICAL RELEVANCE:
      Identification of bony structures in the fetus is useful in estimating the time
      to parturition in queens.

PMID- 14664449
TI  - Use of high-resolution ultrasound as a diagnostic tool in veterinary
      ophthalmology.
AB  - The recent development of a 20-MHz, high-frequency ultrasound probe has allowed
      tissue to be visualized at resolutions of 20 to 80 microm, which is similar to a
      low-power histologic view. This high degree of resolution, however, limits tissue
      penetration to 5 to 10 mm, which is ideal for examination of the anterior segment
      of the eye. The detail provided by high-resolution ultrasound readily permits the
      clinician to distinguish between various anterior segment entities that may
      appear similar but are treated quite differently, such as anterior uveal tumors,
      iridociliary cysts, and iris bombe. High-frequency ultrasound is also a valuable
      aid in creating a surgical plan for treatment of ocular disorders in which the
      cornea is opaque, such as feline corneal sequestrum and tumor invasion into the
      cornea. Other applications of this technology include elucidation of the
      pathogenesis of glaucoma in veterinary patients and evaluation of regions of the
      lens that are difficult to examine directly.

PMID- 14664450
TI  - Diagnostic peritoneal lavage for identification of blastomycosis in a dog with
      peritoneal involvement.
AB  - A 6-year-old castrated male Dalmatian was evaluated because of hematemesis. The
      dog had lived its entire life in South Dakota and Wyoming and had never traveled
      outside of these states. Results of laboratory testing were compatible with
      iatrogenic acute renal failure and gastrointestinal tract ulceration secondary to
      previous nonsteroidal anti-inflammatory drug and corticosteroid administration.
      Differential diagnoses for clinical signs and laboratory abnormalities that
      existed prior to these treatments included multisystemic infectious or
      inflammatory disease and neoplasia. Four-quadrant abdominocentesis did not yield
      any fluid, but because intra-abdominal disease was still suspected, diagnostic
      peritoneal lavage was performed. Fluid that was obtained was markedly cellular,
      and there were numerous extracellular structures with a round to oval shape; a 1
      microm-thick, clear-staining capsule; a basophilic interior; and broad-based
      budding. Organisms were consistent with Blastomyces spp, and fungal culture
      yielded Blastomyces dermatitidis. Treatment with liposomal amphotericin B and
      itraconazole was recommended but could not be initiated because of the client's
      financial constraints. At necropsy, disseminated blastomycosis involving the
      stomach, small intestines, urinary bladder, omentum, mesentery of the small
      intestine, and abdominal wall musculature was seen. To our knowledge, peritoneal
      involvement has not been reported in dogs with blastomycosis, and
      gastrointestinal tract involvement has only rarely been reported. Findings in
      this dog suggest that diagnostic peritoneal lavage may be a useful technique in
      determining the cause of infectious peritonitis when the amount of abdominal
      fluid is below the limit of detection for abdominocentesis.

PMID- 14664451
TI  - Demographic, clinical, and radiographic features of bronchiectasis in dogs: 316
      cases (1988-2000).
AB  - OBJECTIVE: To determine demographic, clinical, and radiographic features of
      bronchiectasis in dogs. DESIGN: Retrospective study. ANIMALS: 289 dogs identified
      through the Veterinary Medical Database (VMDB) and 27 dogs examined at the North
      Carolina State University Veterinary Teaching Hospital. PROCEDURE: Demographic
      characteristics of dogs identified through the VMDB were compared with
      characteristics of the entire population of dogs entered in the VMDB. Medical
      records of dogs examined at the teaching hospital were reviewed; the diagnosis
      was confirmed through review of thoracic radiographs. RESULTS: Analysis of data
      from the VMDB indicated that American Cocker Spaniels, West Highland White
      Terriers, Miniature Poodles, Siberian Huskies, English Springer Spaniels, and
      dogs > 10 years old had an increased risk of bronchiectasis. Among dogs examined
      at the teaching hospital, coughing was the most common clinical sign. There was
      evidence for excessive airway mucus but not hemorrhage. A variety of bacterial
      organisms were isolated from tracheal wash and bronchoalveolar lavage samples. On
      thoracic radiographs, cylindrical bronchiectasis, generalized disease, and right
      cranial lung lobe involvement were most common. Seven of 14 dogs for which follow
      up radiographs were available did not have any progression of radiographic
      lesions. Median duration of clinical signs prior to diagnosis of bronchiectasis
      was 9 months (range, 1 day to 10 years). Median survival time was 16 months
      (range, 2 days to 72 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that despite substantial clinical abnormalities, dogs with bronchiectasis may
      survive for years. Certain purebred dogs and older dogs may have an increased
      risk of developing bronchiectasis.

PMID- 14664452
TI  - Association of breed with the diagnosis of congenital portosystemic shunts in
      dogs: 2,400 cases (1980-2002).
AB  - OBJECTIVE: To determine the annual and overall proportion of diagnoses of
      congenital portosystemic shunts (CPSS) in dogs and identify breeds at increased
      risk for CPSS. DESIGN: Retrospective study. ANIMALS: 2,400 dogs with CPSS from
      veterinary teaching hospitals that reported to the Veterinary Medical Database
      (VMDB) from January 1, 1980 to February 28, 2002. PROCEDURE: The proportion of
      diagnoses of CPSS was calculated for all dogs and each breed recorded in the VMDB
      annually and for the 22.2-year period. Odds ratios and adjusted confidence
      intervals were calculated for breeds with at least 100 accessions by comparing
      odds of each breed with a diagnosis of CPSS with that of mixed-breed dogs.
      RESULTS: Congenital portosystemic shunts were reported in 0.18% of all dogs and
      0.05% of mixed-breed dogs. The proportion of diagnoses of CPSS increased from 5
      in 10,000 dogs in 1980 to 5 in 1,000 dogs in 2001. Yorkshire Terriers had the
      greatest total number of diagnoses of CPSS. Thirty-three breeds were
      significantly more likely to have a diagnosis of CPSS, compared with mixed-breed
      dogs. The greatest proportions of diagnoses were found in Havanese (3.2%),
      Yorkshire Terriers (2.9%), Maltese (1.6%), Dandie Dinmont Terriers (1.6%), and
      Pugs (1.3%). CONCLUSIONS AND CLINICAL RELEVANCE: Certain breeds appear to be at
      increased risk for CPSS, compared with mixed-breed dogs. The increased odds
      ratios among specific breeds support the hypothesis of a genetic predisposition
      for CPSS. Clients and veterinarians should consider appropriate diagnostic tests
      for dogs with clinical signs and those used for breeding from breeds with
      increased risk of CPSS.

PMID- 14664453
TI  - Detection of Salmonella organisms and assessment of a protocol for removal of
      contamination in horse stalls at a veterinary teaching hospital.
AB  - OBJECTIVES: To assess methods of detecting environmental contamination with
      Salmonella organisms and evaluate a cleaning and disinfection protocol for horse
      stalls in a veterinary teaching hospital. DESIGN: Original study. SAMPLE
      POPULATION: 37 horses with diarrhea likely to be caused by Salmonella infection
      and their stall environments. PROCEDURES: Fecal samples were collected from
      horses daily during hospitalization; samples were obtained from stall sites after
      cleaning and application of disinfectants. Fecal and environmental samples were
      cultured for Salmonella spp and tested via polymerase chain reaction (PCR) assay
      to detect Salmonella DNA. RESULTS: 1 horse died and 2 were discharged prior to
      sample collection. Fecal samples from 9 of 34 horses yielded growth of Salmonella
      organisms on bacteriologic culture, and 23 yielded positive results via PCR assay
      on > or = 1 occasion. Among environmental samples from 21 stalls, salmonellae
      were detected at > or = 1 stall site on 6 of 78 occasions, and > or = 1 stall
      site yielded positive results via PCR assay on 69 of 77 occasions. Salmonella DNA
      was detected more frequently in samples of stall drains, cracks, and corners.
      Salmonella spp were cultured from samples of 3 stalls after both initial and
      second cleaning and disinfection cycles, but no organisms were detected in
      samples obtained after use of a peroxygen disinfectant. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that stalls in which horses with salmonellosis were
      housed should only be used to accommodate newly hospitalized horses after samples
      (collected after 2 cycles of cleaning and disinfection) from drains, cracks, and
      corners yield negative results on bacteriologic culture.

PMID- 14664454
TI  - Analysis of risk factors for recurrent airway obstruction in North American
      horses: 1,444 cases (1990-1999).
AB  - OBJECTIVE: To identify risk factors for recurrent airway obstruction (RAO) among
      horses examined at veterinary teaching hospitals in North America. DESIGN:
      Retrospective case-control study. ANIMALS: 1,444 horses with RAO and 1,444
      control horses examined for other reasons. PROCEDURE: The Veterinary Medical
      Database was searched for records of horses in which RAO was diagnosed. A control
      group was identified by randomly selecting a horse with a diagnosis other than
      RAO that matched the institution and year of admission for each of the horses
      with RAO. Information obtained included hospital, admission year and month, age,
      sex, breed, and discharge status. The association between risk factors and
      diagnosis of RAO was estimated with logistic regression models. RESULTS: The risk
      of RAO increased significantly with age, with horses > or = 7 years old being 6
      to 7 times as likely to have RAO as were horses < or = 4 years old. Thoroughbreds
      were 3 times as likely to have RAO as were ponies. Horses were 1.6 and 1.5 times
      as likely to be examined because of RAO during winter and spring, respectively,
      than they were during summer. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that RAO was more likely to be diagnosed in females, horses > or = 4 years old,
      and Thoroughbreds and that RAO has a seasonal distribution.

PMID- 14664455
TI  - Diagnostic modalities for infectious diseases.
AB  - The role of the microbiology laboratory is essential to successful provision of
      patient care. Obtaining appropriate laboratory data allows clinicians the best
      opportunity to arrive at a definitive diagnosis in a timely manner, eliminates
      the need for further tests, and can offer specific treatment approaches with
      maximal potential for success. This article discusses the laboratory procedures
      useful for diagnosis of oral or maxillofacial infections, including collection
      and transport of microbial specimens, representative techniques and methods
      available for culture and diagnostic assays, diagnostic laboratory principles for
      specific types of microbial etiologies, antimicrobial sensitivity, quality
      control issues, and evaluation of reported findings.

PMID- 14664456
TI  - Antibiotic resistance.
AB  - Through billions of years of evolution, microbes have developed myriad defense
      mechanisms designed to ensure their survival. This protection is readily
      transferred to their fellow life forms via transposable elements. Despite very
      early warnings, humans have chosen to abuse the gift of antibiotics and have
      created a situation where all microorganisms are resistant to some antibiotics
      and some microorganisms are resistant to all antibiotics. When antibiotics are
      used, six events may occur with only one being beneficial: when the antibiotic
      aids the host defenses to gain control and eliminate the infection.
      Alternatively, the antibiotic may cause toxicity or allergy, initiate a
      superinfection with resistant bacteria, promote microbial chromosomal mutations
      to resistance, encourage resistance gene transfer to susceptible species, or
      promote the expression of dormant resistance genes.

PMID- 14664457
TI  - Immunizations and oral health care providers.
AB  - Two very successful approaches aimed at preventing infectious diseases acquired
      in the dental office have introduced more vigilant infection control and barrier
      techniques as well as the use of specific immunizations. Special consideration is
      given to the subgroup of dental professionals at increased risk for common
      diseases that may prevail because of the location and demographics of their
      practices. A brief review of the basic principles of immunology and immunization
      is covered as well as immunizations and the medically compromised oral health
      care worker, the medically compromised patient, new vaccines that may be in the
      offing, and the future role of immunization for dentists.

PMID- 14664458
TI  - Antibiotic prophylaxis: problems in paradise.
AB  - The age of antibiotic prophylaxis may be receding into its twilight years because
      the assumption upon which it was based has not proved generally true. Although
      antibiotics treat infections, limited benefit has been demonstrated in preventing
      infections. These are two entirely different biologic entities, a distinction
      which appears to have gone unappreciated by many for more than 50 years. If the
      principles of antibiotic prophylaxis established more than 40 years ago had been
      assiduously followed, many of its abuses could have been avoided. This may not
      have stopped our legal colleagues, but it would have been worth an effort on
      behalf of our patients. It is likely that the massive overuse of antibiotics as
      litigation prevention has contributed to the global epidemic of antibiotic
      resistant micro-organisms and an unknown number of serious adverse effects to the
      antibiotics themselves. Even with this abuse, much money has still flowed from
      defendant to plaintiff. Substantial data exist that antibiotics do not prevent
      bacteremias. The absolute risk rate for bacterial endocarditis after dental
      treatment even in at-risk patients is very low. Antibiotic prophylaxis for
      surgical infections requires specific dosing schedules (perioperative surgical
      prophylaxis) to be successful. Hopefully the difficulties presented herein
      regarding antibiotic prophylaxis will lead to their more enlightened use in the
      future.

PMID- 14664459
TI  - Occupational exposures to human immunodeficiency virus, hepatitis B virus, and
      hepatitis C virus: risk, prevention, and management.
AB  - Current data indicate that the risk for transmitting bloodborne pathogens in
      dental health care settings is low. Pre-exposure hepatitis B vaccination and the
      use of standard precautions to prevent exposure to blood are the most effective
      strategies for preventing DHCP from occupational infection with HIV, HBV or HCV.
      Each dental health care facility should develop a comprehensive written program
      for preventing and managing occupational exposures to blood that: (1) describes
      the types of blood exposures that may place DHCP at risk for infection; (2)
      outlines procedures for promptly reporting and evaluating such exposures; and (3)
      identifies a health care professional who is qualified to provide counseling and
      perform all medical evaluations and procedures in accordance with the most
      current USPHS recommendations. Finally, resources should be available that permit
      rapid access to clinical care, testing, counseling, and PEP for exposed DHCP and
      the testing and counseling of source patients.

PMID- 14664460
TI  - Infection control.
AB  - Information resources from a variety of governmental agencies and professional
      organizations are available to facilitate development of site-specific infection
      control programs. Using a strategic approach to organize and apply the
      information can result in a comprehensive and effective infection control
      program.

PMID- 14664461
TI  - Immune suppression and considerations for dental care.
AB  - Immunocompromised individuals present a challenge to oral health care providers.
      As the spectrum of patients with dysfunctional immune responses continues to
      broaden, practitioners should be able to identify these patients, understand the
      potential for complications, and manage their dental care safely and effectively.
      This article reviews various immune deficiencies, addresses complications that
      may result from an individual's immune status, and discusses dental
      considerations for these patients.

PMID- 14664462
TI  - Dentistry and bioterrorism.
AB  - Dentistry's role in responding to bioterrorism and other catastrophic events is
      evolving and may involve a wide range of activities. Organized dentistry. local
      dental societies. and interested individuals should make local emergency response
      planners aware of the services the dental profession can provide and should work
      to integrate dental resources to strengthen the disaster response capacity of
      community health care systems. With effective planning, education, and training,
      dentists can play a significant role in responding to acts of bioterrorism or
      other unforeseen events.

PMID- 14664463
TI  - Legal issues for healthcare workers with bloodborne infectious disease.
AB  - The risk of bloodborne disease transmission in dental settings is very low.
      Available data support the low risk of transmission. The rate of occupational
      injuries among dental health care workers has decreased over the last decade and,
      other than the 1990 case of HIV transmission in a dental office, there have been
      no additional reports of bloodborne disease transmission by dental health care
      workers. However, public policy and judicial decisions focus less on science and
      more on emotion. Although many infection control organizations have updated their
      policies to remain current with science, the USPHS's policy remains as released
      in 1991. It would be prudent for these guidelines to be updated to reflect
      current scientific evidence and be inclusive for all bloodborne pathogens.

PMID- 14664464
TI  - The interleukin-1 gene family in multiple sclerosis susceptibility and disease
      course.
AB  - Multiple sclerosis (MS) is a chronic disease of presumed autoimmune origin with a
      considerable polygenic influence. We have previously observed that a specific
      allele combination in genes of the interleukin-1 (IL-1) family influenced the
      progression rate in MS. We have considerably expanded our patient population (492
      MS patients and 228 controls). In the present study, we investigated the role of
      the IL-IA--889, IL-1B--511, IL-1B f3953 and IL-1RN VNTR gene polymorphisms in MS.
      In addition, we performed preliminary analyses on longitudinal magnetic resonance
      imaging (MRI) data. We found no associations between the polymorphisms and
      susceptibility to MS or clinical features. In addition, we observed no
      significant effect of the polymorphisms on brain or lesion volumes, Based on our
      data and those from the literature, one can conclude that there is currently no
      evidence to support a role for the IL-1 genes in MS.

PMID- 14664465
TI  - Blood-brain barrier disruption in multiple sclerosis.
AB  - The blood-brain barrier (BBB) is a complex organization of cerebral endothelial
      cells (CEC), pericytes and their basal lamina, which are surrounded and supported
      by astrocytes and perivascular macrophages. Collectively these cells separate and
      form the compartments of the cerebral vascular space and the cerebral
      interstitium under normal conditions. Without the BBB, the 'interior milieu' of
      the central nervous system (CNS) would be flooded by humoral neurotransmitters
      and formed blood elements that upset normal CNS functions and lead to
      vascular/neural injury. Dysregulation of the BBB and transendothelial migration
      of activated leukocytes are among the earliest cerebrovascular abnormalities seen
      in multiple sclerosis (MS) brains and parallel the release of inflammatory
      cytokines/chemokines. Mechanisms for breakdown of the BBB in MS are incompletely
      understood, but appear to involve direct effects of these cytokines/ chemokines
      on endothelial regulation of BBB components, as well as indirect
      cytokine/chemokine-dependent leukocyte mediated injury. Unique endothelial
      structural features of the BBB include highly organized endothelial tight
      junctions, the absence of class II major histocompatibility complex, abundant
      mitochondria and a highly developed transport system in CEC. Exposure of
      endothelium to proinflammatory cytokines (IFN-gamma, TNF-alpha and IL-1beta)
      interrupts the BBB by disorganizing cell-cell junctions, decreases the brain
      solute barrier, enhances leukocyte endothelial adhesion and migration as well as
      increases expression of class II MHC and promotes shedding of endothelial
      'microparticles' (EMP). In this review we examine interactions between
      cytokines/chemokines, activated leukocytes, adhesion molecules and activated CEC
      in the pathogenesis of BBB failure in MS.

PMID- 14664466
TI  - Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia.
AB  - We describe eight patients with associated multiple sclerosis (MS) and myasthenia
      gravis (MG). Patients were less than 50 years old at the time of onset, and seven
      were female. The clinical course of both MS and MG was mild in most patients. To
      our knowledge, this represents the largest reported series. We provide further
      evidence for a nonrandom association of these two diseases and discuss common
      mechanisms of pathogenesis.

PMID- 14664467
TI  - MRI/MRS of corpus callosum in patients with clinically isolated syndrome
      suggestive of multiple sclerosis.
AB  - Atrophy of corpus callosum (CC) related to axonal loss has previously been
      observed in patients at the early stage of clinically definite multiple sclerosis
      (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no
      data concerning the onset of atrophy of CC are currently available. The purpose
      of this study is to determine if damage in callosal tissue was present at the
      earliest stage of MS, in a subgroup of patients presenting with a clinically
      isolated syndrome suggestive of MS (CISSMS), fulfilling the dissemination in
      space criteria according to McDonald. Magnetic resonance imaging (MRI) and
      magnetic resonance spectroscopy (MRS) techniques were applied to measure CC
      volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl
      aspartate/choline-containing compounds (NAA/Cho) ratio, N-acetyl aspartate/total
      creatine (NAA/Cr) ratio and Cho/Cr ratio inside the CC of 46 CISSMS patients and
      24 sex- and age-matched controls. No atrophy of CC was observed in the CISSMS
      group. CC of patients was characterized by decreased MTR and increased MD. No
      change in the NAA/Cr ratio was observed while the NAA/Cho ratio decreased and
      Cho/Cr ratio increased in the splenium and the central anterior part of CC. These
      abnormalities were present in patients with, but also without, macroscopic
      lesions inside the CC. Our results indicate that diffuse structural and metabolic
      changes, which may be interpreted as representing predominantly myelin pathology,
      occur in the CC at the earliest stage of MS before any atrophy is detected.

PMID- 14664468
TI  - Disability in multiple sclerosis is related to normal appearing brain tissue MTR
      histogram abnormalities.
AB  - BACKGROUND: Magnetization transfer ratio (MTR) histogram analysis provides a
      global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in
      normal appearing brain tissue (NABT) provide quantitative information on the
      extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic
      resonance imaging (MRI). AIMS: 1) To compare the MTR histograms from NABT across
      a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR)
      MS (including newly diagnosed and benign subgroups) and secondary progressive
      (SP) MS. 2) To determine the relationship between clinical disability and NABT
      MTR histograms. METHODS: 2D spin echo magnetization transfer imaging was
      performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR
      histograms were acquired for NABT after extracting lesions and cerebrospinal
      fluid (CSF). T2W images were used to measure the brain parenchymal fraction (BPF)
      and T2 lesion load. RESULTS: MS patients had a disease duration ranging from 0.5
      to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0
      to 8.5. There was a significant decrease in NABT mean MTR (+/- standard
      deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P
      < 0.001) with an effect size of 2.56. The reduction in NABT mean MTR varied among
      patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5%
      for benign MS, compared with controls. NABT mean MTR correlated significantly
      with T2 lesion load (r = -0.82) and BPF (r = 0.58). EDSS score correlated with
      NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59).
      Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined
      only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease
      duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P <
      0.001). CONCLUSIONS: There is evidence of diffuse abnormalities in NABT in
      addition to global brain atrophy in relapse onset MS patients, including those
      with recently diagnosed RRMS and benign MS. The abnormalities are greatest in
      patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are
      all partly correlated; the processes marked by these MR measures all contribute
      to disability in MS, providing complementary information relevant to the complex
      pathological processes that occur in MS.

PMID- 14664469
TI  - Phosphodiesterase inhibitors suppress IL-12 production with microglia and T
      helper 1 development.
AB  - The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12
      production by microglia, antigen-presenting cells in the central nervous system
      (CNS), were examined to learn how they affect T cell differentiation in the CNS.
      PDEIs significantly suppressed the microglial IL-12 production, as determined by
      reverse transcriptase-polymerase chain reaction for IL-12 p35 and p40 mRNA
      expression and by an ELISA specific for IL-12 functional heterodimer, p70. In
      addition, the PDEI ibudilast also suppressed interferon-gamma, but not IL-4 or IL
      10, production by myelin oligodendrocyte glycoprotein (MOG)-specific T cells
      reactivated with MOG in the presence of microglia. Thus, PDEIs may also suppress
      differentiation of T helper 1 (Th1) in the CNS. PDEIs can be of use for future
      therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.

PMID- 14664470
TI  - Cytapheresis with a filter for selective removal of CD4+ T cells in experimental
      autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a major animal model of human
      multiple sclerosis (MS). CD4+ T cells are thought to play a pivotal role in the
      pathogenesis of EAE and MS. In order to investigate the depletion of CD4+ T cells
      from the systemic circulation as an effective strategy for the treatment of MS,
      we performed extracorporeal CD4+ T cell adsorption, using a filter to which anti
      CD4+ antibody is immobilized as a ligand, in adoptively transferred EAE. Rats
      treated with CD4+ T cell removal filter (CD4RF) exhibited milder clinical signs
      of EAE and earlier recovery than those receiving sham treatment. Moreover, the
      thymic cells from EAE rats treated with CD4RF exhibited a suppressed
      proliferative response and IFN-gamma production to myelin basic protein. These
      results suggest that depletion of CD4+ T cells from the systemic circulation by
      extracorporeal treatment is a potentially useful strategy for treatment of acute
      phase and relapsing MS.

PMID- 14664471
TI  - Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in
      a six-year organized multiple sclerosis trial.
AB  - The aim of this study was to assess the long-term safety and efficacy of
      glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received
      active treatment versus those on placebo for approximately 30 months (24-35
      months) before receiving GA during a six-year organized, prospective open label
      study. Entry required two relapses in the previous two years and an Expanded
      Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally
      randomized to daily subcutaneous GA, 20 mg, or to placebo. After approximately 30
      months, 208 patients continued in an open label study: 101 continued on GA and
      107 switched from placebo to active drug. Groups were well matched at
      randomization and entry to the open label study. Patients always on GA showed a
      steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over
      the entire six years (95% CI = 0.34-0.51), a 72% reduction (P = 0.0001). They
      averaged a relapse every four + years (yearly rate 0.23 in year six) and 26/101
      remain relapse free. Patients did less well if on placebo for 30 months, but
      relapses then declined, and by year six the rates were similar. Of patients
      always on GA, 69% showed neurological improvement of > or = 1 EDSS steps or
      remained stable compared with 57% if GA treatment was delayed. Of relapse-free
      patients always on GA over six years, only three of 26 (11%) were worse by > or =
      1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P
      < 0.03). Disability, measured every six months, showed that the group of patients
      always on GA was relatively stable over the six years, while the group who
      received placebo for the first two-and-a-half years did significantly less well.
      Daily injections of GA were well tolerated. This longest ever organized MS
      treatment trial shows that delaying therapy with GA increases the risk of
      neurologic disability, reinforcing the rationale for using GA as a first-line
      treatment early in the course of relapsing-remitting MS.

PMID- 14664472
TI  - Antibodies to glatiramer acetate do not interfere with its biological functions
      and therapeutic efficacy.
AB  - Glatiramer acetate (GA) previously known as Copolymer 1 (Cop 1), a synthetic
      amino acid copolymer, suppresses experimental autoimmune encephalomyelitis (EAE)
      and shows a beneficial effect in relapsing-remitting type of multiple sclerosis
      (MS). GA acts as a specific immunomodulator by binding to MHC Class II molecules,
      inducing specific T suppressor (Ts) cells and interfering with T cell responses
      to myelin antigens. MS patients treated with GA developed GA reactive antibodies,
      which peaked at three months and decreased at six months. In order to find out
      whether anti-GA antibodies may neutralize the therapeutic effect of GA, we tested
      both polyclonal (mouse and human) and monoclonal GA specific antibodies for their
      ability to interfere with the biological activity of GA in several assay systems.
      None of the antibodies interfered with GA activities either in vitro (binding to
      MHC molecules and T cell stimulation) or in vivo (blocking of EAE). Furthermore,
      53 samples of sera obtained from 34 MS patients that participated in the open
      label trial in Israel, and all developed GA specific antibodies, were tested for
      their ability to inhibit the proliferation response of GA specific Ts cell clone
      and to interfere with GA competitive inhibition of the response to peptide 84-102
      of myelin basic protein (MBP). None of the sera inhibited and some even enhanced
      the in vitro activities of GA. Furthermore, representative MS sera with high
      titer of GA reactive antibodies did not neutralize the biological activities of
      GA and did not inhibit Th2 cytokine secretion by human GA specific clone. These
      results are consistent with the findings that the therapeutic effect of GA is not
      affected by GA reactive antibodies and is sustained upon long term treatment.

PMID- 14664473
TI  - Bone status in multiple sclerosis: beyond corticosteroids.
AB  - The aim of this study was to determine the possible factors affecting bone
      mineral density (BMD) in multiple sclerosis (MS). In this cross-sectional study,
      65 clinically definite MS patients and 72 comparable controls were prospectively
      evaluated. To assess bone mineral metabolism in MS, the BMD of the lumbar spine
      and hip (femoral neck, trochanter and total) was measured by dual-energy X-ray
      absorptiometry, and serum vitamin D and parathyroid hormone levels and
      biochemical markers of bone turnover were also evaluated. MS patients had
      significantly lower BMD values than the control group at all measurement sites.
      There was a significant correlation between the disease duration and BMD values
      at the trochanter in women with MS. A correlation between femoral BMD values and
      functional status in women was also detected. There was no relationship between
      bone biochemical markers and BMD, except a negative correlation between bone
      alkaline phosphatase and trochanter BMD. Both disability and disease duration
      have an influence on BMD of the MS patients, whereas no significant correlation
      between glucocorticoid use and BMD was observed.

PMID- 14664474
TI  - Chronic pain in a large community sample of persons with multiple sclerosis.
AB  - INTRODUCTION: This study examined the prevalence, intensity, interference, and
      biopsychosocial correlates of pain in a large community-based sample of persons
      with multiple sclerosis (MS). METHODS: Mail surveys were returned by 442 members
      of the King County (WA) MS Association. Average pain intensity, pain-related
      activity interference, depressive symptoms and severity of MS were assessed.
      RESULTS: Forty-four percent reported persistent, bothersome pain in the three
      months prior to completing the survey. Participants with pain reported an average
      pain intensity rating of 5.2 (SD = 2.3) on the 0 (no pain) to 10 (pain as bad as
      could be) scale. Twenty-seven percent reported severe pain (score of 7-10), while
      51% of those with pain rated the interference of their pain with daily activities
      as none to minimal. Twenty percent reported severe interference in activities as
      a result of pain. In multivariate modeling, MS illness severity, marital status,
      and self-ratings of overall health were significantly associated with pain
      related interference with activities. CONCLUSIONS: Approximately a fourth of this
      sample described having a chronic pain problem characterized by severe pain
      intensity and significant pain-related interference with activities. Disability
      due to pain may be more important than previously recognized for the MS
      population.

PMID- 14664475
TI  - The 'Impact on Participation and Autonomy': acceptability of the English version
      in a multiple sclerosis outpatient setting.
AB  - To elicit the opinion of multiple sclerosis (MS) patients about the acceptability
      of a newly designed participation questionnaire--the 'Impact on Participation and
      Autonomy' (IPA), 35 MS outpatients who had completed an English version of the
      IPA questionnaire (IPA-E) were interviewed. Patients were recruited consecutively
      from outpatients attending the MS clinic. They were invited to answer 15 short
      questions during a 20-minute interview after signing a consent form and
      completing the IPA-E questionnaire. Completion time of the IPA-E questionnaire
      was 19.3 +/- 4.7 minutes. Most respondents believed that the IPA-E items were
      easy or very easy to understand (83%), relevant (more than 74%), not embarrassing
      (more than 97%) and 94% considered that no items should be removed. Three
      additional topics were suggested: 'looking after children; 'the extent of
      information on current services'and information about 'treatment progress' Among
      the eight domains of the IPA, most respondents considered mobility to be the most
      important and education the least important. The IPA-E was found to be acceptable
      and relevant to a sample of MS outpatients, although it could have been enhanced
      by items on parental or family roles.

PMID- 14664476
TI  - Depressive symptoms in a treated multiple sclerosis cohort.
AB  - BACKGROUND: Recent side effect data from clinical trials of interferon beta in
      multiple sclerosis (MS) have failed to confirm that these medications are
      associated with an increased risk of depression. However, these studies have used
      highly selected samples and the results may not be generalizable to real world
      settings. METHODS: Clinical data on subjects from southern Alberta who have
      applied for, or are receiving, public reimbursement for MS treatment are
      maintained in a database at the University of Calgary Multiple Sclerosis Clinic.
      Depression ratings obtained using the Center for Epidemiological Studies
      Depression Rating Scale (CES-D) are included in this database. In the current
      analysis, these longitudinal data were used to determine whether depressive
      symptoms were associated with disease-modifying treatments. RESULTS: At baseline,
      ratings were available for 163 subjects. Those choosing interferon beta resembled
      those choosing glatiramer acetate in most respects. During follow-up, no
      differences were observed in the prevalence or incidence of depression and CES-D
      scores were not found to differ between the treatment groups. CONCLUSIONS: The
      failure to identify higher rates of depression both in previous intervention
      studies and in the current observational study provides confirmation that these
      drugs are not substantially associated with the occurrence of depression.

PMID- 14664477
TI  - Validity and reliability of the MSQLI in cognitively impaired patients with
      multiple sclerosis.
AB  - Multiple sclerosis (MS) has important effects on quality of life but it is
      unknown how cognitive impairment affects the ability to assess or report this.
      Our objective was to determine whether cognitive impairment negatively affects
      the construct validity and the reliability of the Multiple Sclerosis Quality of
      Life Inventory (MSQLI). A neuropsychological test battery and the Multiple
      Sclerosis Functional Composite (MSFC) were administered to a sample of 136
      patients referred for cognitive testing by their neurologists. Age, sex,
      education and ethnicity-adjusted T scores were calculated for each cognitive
      variable. Cognitive impairment was defined as any T score less than the fifth
      percentile. The MSQLI was administered prior to neuropsychological testing and
      readministered one to four weeks later: Correlations between the MSFC and the SF
      36 were determined and compared between the cognitively impaired and unimpaired
      groups as the main test of construct validity. Test-retest and internal
      consistency reliability of each of the scales were compared for the impaired and
      unimpaired groups. Seventy-six (56%) patients were cognitively impaired.
      Construct validity and internal consistency reliability did not differ between
      the cognitively impaired and unimpaired groups. Test retest reliability was lower
      for the bladder and vision scales in the impaired group, but remained acceptable
      for the bladder scale (r > 0.7). Cognitive impairment, a common MS manifestation,
      does not appear to reduce the reliability or validity of the MSQLI as a patient
      self-report measure of health status and quality of life.

PMID- 14664478
TI  - Towards a european network for multiple sclerosis trials (ENMST).
AB  - Quality standards for clinical studies in the field of multiple sclerosis (MS)
      have improved significantly, to the great benefit of patients. This development
      has been accompanied by soaring costs and ever increasing complexity, with
      industry-independent trials having become virtually impossible. We propose
      establishing a European network that would include expertise in all the relevant
      aspects of MS treatment trials. In a stepwise approach, all interested active
      centres across Europe should be recruited into the network, based on agreement
      upon common scientific standards and quality requirements. Three main goals are
      discussed: to facilitate identification of potentially useful agents for MS
      treatment; to establish protocols for the interaction between investigators and
      industry; and to identify common standards and a core set of data to allow for
      comparisons of MS trials. Collaboration with existing international organizations
      and institutions, especially the Sylvia Lawry Centre for MS Research, as well as
      with similar initiatives in North America and other parts of the world is
      envisaged.

PMID- 14664479
TI  - Acute verbal dyspraxia, a rare presentation in multiple sclerosis: a case report
      with MRI localization.
AB  - Cortical speech disorders rarely occur in multiple sclerosis (MS). We report a
      patient with relapsing-remitting MS, who presented with acute verbal dyspraxia.
      Magnetic resonance imaging (MRI) demonstrated an acute T2/Flair hyperintense,
      primarily white matter lesion underlying the middle third of the inferior frontal
      gyrus. The verbal dyspraxia cleared beginning 48 hours after the initiation of iv
      dexamethasone. Follow-up MRI demonstrated qualitative and quantitative diminution
      of the hyperintensity. This is the first report of a clinically definite MS
      patient with acute verbal dyspraxia. Moreover, there was a suggestive
      localization of verbal praxis to Brodmann areas 44/45.

PMID- 14664480
TI  - The race to China and implications for global labor standards.

PMID- 14664481
TI  - Occupational health and safety legislation and implementation in China.
AB  - This article reviews the current statistics of employment and work-related
      injuries and illness in China, as well as the history of occupational health and
      safety legislation in the country. Comprehensive, newly promulgated workplace
      health and safety legislation is described, and the specific responsibilities of
      employers, government agencies, trade unions, and employees are detailed. The
      government's implementation plan for this and prior legislation is also outlined.

PMID- 14664482
TI  - "The absence of rigor and the failure of implementation": occupational health and
      safety in China.
AB  - Despite government concern with occupational health and safety (OHS) in China and
      the promulgation of new laws and regulations in 2002, a lack of rigor and lax
      implementation are major impediments to improvements in workplace safety. The
      article highlights important elements from the new Work Safety Law and the Law on
      the Prevention and Cure of Occupational Diseases, then analyzes key issues
      arising from bureaucratic excesses, the impact of government restructuring,
      continuing confusions and contradictions in government responsibility for OHS,
      and ongoing questions about the official duties and responsibilities of employing
      units, workers, and the trade union.

PMID- 14664483
TI  - Rules and regulations in Chinese factories.

PMID- 14664484
TI  - Occupational lung disease in China.
AB  - Occupational lung disease has been a major public health problem in China. The
      recently transformed industrial structure and expansion of the industrial labor
      force, accompanying the rapid industrialization and economic growth, pose both
      tremendous challenges and opportunities for occupational health policy and
      research. New occupational health problems are emerging, while the traditional
      occupational lung disease continued to occur. Simultaneously, relevant scientific
      research and professional activities have accelerated notably. The progress and
      achievement in occupational health research are creating more powerful forces in
      eliminating industrial hazards and protecting workers' health in China.

PMID- 14664485
TI  - China's factory floors: an industrial hygienist's view.
AB  - Determinants of workplace health and safety in China, including work
      organization, composition of the workforce, production regimens, lack of
      independent worker representation, and the status of government regulatory
      enforcement, are described and analyzed. The findings of reports of
      nongovernmental organizations and media articles are summarized. Key markers of
      working conditions in export-sector factories, i.e., accident and safety program
      compliance rates, chemical and noise exposures, and machine guarding issues, are
      analyzed. Four factors for improving workplace health and safety are proposed: 1)
      employer commitment and implementation of effective health and safety programs on
      a plant level; 2) Chinese government enforcement of regulations; 3) meaningful
      involvement of workers in plant health and safety programs; and 4) continued
      involvement of international professionals and "civil society" both to pressure
      multinational corporations and the Chinese government and to provide technical
      assistance and resources for building the capacity of employers, workers, and
      government agencies to improve factory working conditions in the world's fastest
      growing economy.

PMID- 14664486
TI  - Chinese workers pay personal price for employer noncompliance with labor safety
      rules.

PMID- 14664487
TI  - Nursing rooms as an indicator of demographic change among migrant workers in
      Guangdong Province, China.

PMID- 14664488
TI  - Why China matters in global electronics.

PMID- 14664489
TI  - Development of a cancer research study in the Shanghai textile industry.
AB  - This article describes the development of a cancer study among Shanghai textile
      workers. Due to the organization of work between 1949 and the 1980s, and superior
      record-keeping practices, it is possible to track textile workers' job tasks and
      workplace exposures over virtually the entirety of their working lives. The
      authors' experiences utilized important relationships developed over more than
      ten years to access work exposures and cancer outcomes. Initial findings indicate
      a significantly increased risk for breast cancer for women employed in cotton,
      wool, mixed-fiber, and machine-maintenance sectors. This project is an example of
      the unique research opportunities to be found in China, and illustrates how these
      data sources may be lost due to ongoing changes in the Chinese economy.

PMID- 14664490
TI  - Developing an action-based health and safety training project in southern China.
AB  - A project brought together international footwear manufacturers, labor rights
      groups, local contract factories, and occupational health professionals to
      strengthen factory health and safety programs in southern China. Steps involved
      in the two-year project, including needs assessment, interviews and focus groups
      with workers and supervisors; design and development of a participatory workshop;
      development of plant-wide health and safety committees in three footwear
      factories; and evaluation project impact, are discussed. The project
      significantly increased occupational safety and health knowledge, and hazards in
      the factories were identified and corrected. Successes and challenges faced by
      three functioning worker-management health and safety committees are discussed.
      Key elements to create effective programs with meaningful participation by
      workers include: 1) developing clear guidelines that enable multi-stakeholder
      groups to collaborate; 2) obtaining top-level management support; 3) building
      workers' knowledge and capacity to fully participate; 4) involving local labor
      rights groups and occupational professionals in support and technical assistance;
      and 5) connecting project goals to larger issues within a country and the global
      economy.

PMID- 14664491
TI  - Workers' participation and their health and safety protection in China's
      transitional industrial economy.
AB  - Chinese workers have inherited from the Maoist era two institutions through which
      they may participate in workplace management--the trade union and the Staff and
      Workers' Representative Congress. This paper analyzes how workers have
      participated in the protection of their health and safety through these
      institutions, describing their functions, on paper, as stipulated by laws and
      regulations, and in practice, in a printing-machinery shareholding company, based
      on an in-depth case study. The impacts of these two institutions have declined
      with industrial economic reform, and the power of the enterprise is shifting
      toward management. China is confronted with serious occupational health and
      safety problems. It is imperative to strengthen the mechanisms that engage
      workers in the prevention of these problems.

PMID- 14664492
TI  - Experiments in transforming the global workplace: incentives for and impediments
      to improving workplace conditions in China.
AB  - This article highlights current economic conditions in China and analyzes
      existing obstacles to improving workplace conditions and labor practices. There
      are significant disincentives to strengthening workplace protections, and
      downward pressures are currently worsening conditions in a number of economic
      sectors. However, there are also potential strategies for motivating
      multinational corporations (MNCs) and Chinese government agencies to improve
      workplace conditions and to implement international and national laws and
      corporate codes of conduct. Four key principles are discussed that hold promise
      for creating incentives and sustainable mechanisms to improve factory conditions:
      transparency, verification, and accountability for MNCs and Chinese government
      agencies, and greatly strengthening worker participation.

PMID- 14664493
TI  - Re: Regulatory Toxicology and Pharmacology.

PMID- 14664494
TI  - Re: Regulatory Toxicology and Pharmacology.

PMID- 14664495
TI  - Health and safety executive inspection of U.K. semiconductor manufacturers.
AB  - Europe plays a major role in the international semiconductor industry, but has
      conducted few studies of the occupational health of its workers. An exception is
      in the United Kingdom, where, in two small studies, the Health and Safety
      Executive (HSE) evaluated some health effects of semiconductor work. Neither of
      these studies, largely restricted to Scotland, produced definitive results, and
      both were misused by industry to assert that they demonstrated no adverse health
      effect on workers. The results of the studies prompted semiconductor industry
      inspections recently completed by the HSE that included chip manufacturers in
      Scotland and other U.K. areas. The results of these inspections are
      disappointing.

PMID- 14664496
TI  - Comments on some aspects of the present IARC practice.

PMID- 14664497
TI  - Lung cancer in MMVF workers--viewpoints on a null-result study.

PMID- 14664498
TI  - IARC downgrading of DEHP.

PMID- 14664499
TI  - IARC and the DEHP quagmire.

PMID- 14664500
TI  - A new tumor-specific antigenic peptide encoded by MAGE-6 is presented to
      cytolytic T lymphocytes by HLA-Cw16.
AB  - "Cancer-germline" genes such as those of the MAGE family are expressed in many
      tumors and in male germline cells, but are silent in normal tissues. They encode
      shared tumor-specific antigens, which have been used in therapeutic vaccination
      trials of cancer patients. MAGE-6 is expressed in more than 70% of metastatic
      melanomas and more than 50% of carcinomas of the lung, esophagus, bladder, and
      head and neck. We report here the identification of a new MAGE-6 antigenic
      peptide, which is recognized by a tumor-specific cytolytic T lymphocyte clone
      isolated from a melanoma patient. The peptide, ISGGPRISY, corresponds to
      positions 293 to 301 of the MAGE-6 protein sequence and is presented by HLA
      Cw1601 molecules.

PMID- 14664501
TI  - Determination of the fungicide validamycin A by capillary zone electrophoresis
      with indirect UV detection.
AB  - Validamycin A, a main component of the antibiotic validamycin complex, which is
      widely used to control sheath blight disease of rice plants, can be determined by
      capillary zone electrophoresis with indirect UV detection. The influence of
      various separation conditions including background electrolyte and modifier
      concentration, pH, and voltage was investigated. By using 10 mM aminopyrine-2 mM
      ethylenediaminetetraacetic acid at pH 5.2 as the carrier electrolyte, high
      efficiency separation of validamycin A was achieved with the number of
      theoretical plates up to 350000 plates/m. The linear range was across 3 orders of
      magnitude. The relative standard deviations for migration times and peak areas
      were less than 0.5 and 3.0%, respectively. The limit of detection for validamycin
      A was 1.0 microg/mL. The average recoveries ranged from 103.0 to 104.8%. This
      method has many advantages as compared with high-performance liquid
      chromatography and micellar electrokinetic capillary chromatography in the
      determination of commercial formulations.

PMID- 14664502
TI  - Determination of the fluoroquinolone enrofloxacin in edible chicken muscle by
      supercritical fluid extraction and liquid chromatography with fluorescence
      detection.
AB  - A supercritical fluid extraction (SFE) method for the extraction of enrofloxacin
      from a chicken breast muscle was examined. A liquid chromatograph, equipped with
      a fluorescence detector, was used for the detection of enrofloxacin. Optimal
      extraction parameters, such as extraction time, supercritical fluid volume,
      modifier concentration, pressure, and temperature, were determined by examining
      SFE recoveries from control muscle samples spiked with enrofloxacin at different
      levels. In all of the experiments, high recovery values were observed, ranging
      from 101 to 104%. The extraction of enrofloxacin from real muscle samples was
      examined in chickens that were treated orally with enrofloxacin. Extraction was
      carried out by the SFE method after each oral treatment and under optimal
      extraction conditions at set intervals over time. The SFE, combined with liquid
      chromatographic analysis, showed that the concentration of enrofloxacin in the
      chicken muscles decreased continuously with time, giving a negligible
      concentration 72 h after the treatment. These results suggest that SFE is a
      useful approach for the extraction of enrofloxacin from chicken breast muscles.

PMID- 14664503
TI  - ELISA for monitoring lipid oxidation in chicken myofibrils through quantification
      of hexanal-protein adducts.
AB  - The objectives of this study were to optimize a monoclonal competitive indirect
      enzyme-linked immunosorbent assay (CI-ELISA) for hexanal detection, optimize
      solubilization and alkylation procedures for the formation of hexanal-protein
      adducts, and compare the ability the CI-ELISA, thiobarbituric acid reactive
      substances assay (TBARS), and a solid-phase microextraction-gas chromatography
      mass spectrometry (GC/MS-SPME) method for monitoring lipid oxidation in freeze
      dried chicken protein. Freeze-dried myofibrils with added methyl linoleate (0.6
      mmol/g of protein) were stored at 50 degrees C at two water activities (a(w) =
      0.30 and 0.75) for 5 days. Hexanal was measured by GC/MS-SPME and CI-ELISA, and
      malonaldehyde by TBARS. At an a(w) of 0.30, 34.7 and 39.7 microg of hexanal/g of
      myofibril were detected by GC/MS-SPME and CI-ELISA, respectively, after 4 days of
      storage. At an a(w) of 0.75, 39.8 and 61.1 microg of hexanal/g of myofibril were
      detected by GC/MS-SPME and CI-ELISA, respectively, after 4 days of storage. The
      CI-ELISA was well correlated with the GC/MS-SPME (r = 0.78) and TBARS (r = 0.87)
      methods. The correlation of the hexanal-specific CI-ELISA to both GC/MS-SPME and
      TBARS verified the ability of the CI-ELISA to be used as an index of lipid
      oxidation, offering the convenience for use in a kit to be utilized within a food
      processing facility.

PMID- 14664504
TI  - Freshness assessments of Moroccan sardine (Sardina pilchardus): comparison of
      overall sensory changes to instrumentally determined volatiles.
AB  - Freshness of ice-stored sardine was assessed by two sensory methods, the quality
      index method (QIM) and the European Union freshness grading system, and by
      instrumental means using the method of aroma extract dilution analysis. Screening
      of sardine potent volatiles was carried out at three freshness stages. In the
      very fresh state, the plant-like fresh volatiles dominated the odor pattern, with
      the exception of methional. Overall odor changes in sardine throughout storage
      correlated with changes in the concentration of some potent volatiles: after 2
      days of ice storage, (Z)-4-heptenal, (Z)-1,5-octadien-3-one, and methional
      imparted an overall "fishy" odor character to sardine, whereas at a lower sensory
      grade (B), the compounds (E)-2-nonenal and (E,Z)-2,6-nonadienal could be, in
      part, associated with the slightly rancid aroma top notes. Trimethylamine was
      detected as a highly volatile odorant using solid-phase microextraction (SPME)
      headspace analysis of refrigerator-stored sardine. Intensity and sensory
      characteristics of some SPME determined volatiles, for example, 3-methylnonane
      2,4-dione, were closely related to overall odor changes. SPME headspace analysis
      may be useful in the characterization of off-flavors in fish.

PMID- 14664505
TI  - Rugged LC-MS/MS survey analysis for acrylamide in foods.
AB  - The described liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      for the detection of acrylamide in food entails aqueous room temperature
      extraction, SPE cleanup, and analysis by LC-MS/MS. The method is applicable to a
      wide variety of foods. [(13)C(3)]acrylamide is the internal standard. The limit
      of quantitation is 10 ppb (microg/kg). Data were obtained in duplicate from >450
      products representing >35 different food types. The variability in analyte levels
      in certain food types suggests that it may be possible to reduce acrylamide
      levels in those foods.

PMID- 14664506
TI  - Determination of flunixin in edible bovine tissues using liquid chromatography
      coupled with tandem mass spectrometry.
AB  - An accurate, reliable, and reproducible assay was developed and validated to
      determine flunixin in bovine liver, kidney, muscle, and fat. The overall recovery
      and percent coefficient of variation (%CV) of twenty-eight determinations in each
      tissue for flunixin free acid were 85.9% (5.9% CV) for liver, 94.6% (9.9% CV) for
      kidney, 87.4% (4.7% CV) for muscle, and 87.6% (4.4% CV) for fat. The theoretical
      limit of detection was 0.1 microg/kg (ppb, ng/g) for liver and kidney, and 0.2
      ppb for muscle and fat. The theoretical limit of quantitation was 0.3, 0.2, 0.6,
      and 0.4 ppb for liver, kidney, muscle, and fat, respectively. The validated lower
      limit of quantitation was 1 ppb for edible tissues with the upper limit of 400
      ppb for liver and kidney, 100 ppb for fat, and 40 ppb for muscle. Accuracy,
      precision, linearity, specificity, ruggedness, and storage stability were
      demonstrated. Briefly, the method involves an initial acid hydrolysis, followed
      by pH adjustment ( approximately 9.5) and partitioning with ethyl acetate. A
      portion of the ethyl acetate extract was purified by solid-phase extraction using
      a strong cation exchange cartridge. The eluate was then evaporated to dryness,
      reconstituted, and analyzed using LC/MS/MS. The validated method is sensitive and
      specific for flunixin in edible bovine tissue.

PMID- 14664507
TI  - Diffusion coefficient of CO(2) molecules as determined by (13)C NMR in various
      carbonated beverages.
AB  - In this paper, the NMR technique was used, for the first time, to accurately
      determine the diffusion coefficient D of CO(2)-dissolved molecules in various
      carbonated beverages, including champagne and sparkling wines. This parameter
      plays an important role concerning the bubble growth during its rise through the
      liquid (see ref 3). The diffusion coefficient of CO(2)-dissolved molecules D was
      compared with that deduced from the well-known Stokes-Einstein equation and found
      to significantly deviate from the general trend expected from Stokes-Einstein
      theory, i.e, D(SE) proportional, variant 1/eta, where D(SE) is the Stokes
      Einstein diffusion coefficient and eta the viscosity of the liquid medium.

PMID- 14664508
TI  - Analysis of ochratoxin a in coffee by solid-phase cleanup and narrow-bore liquid
      chromatography-fluorescence detector-mass spectrometry.
AB  - A method for the analysis of ochratoxin A (OTA) in green and roasted coffee has
      been developed. OTA was extracted from coffee with 1% NaHCO(3), and the extract
      was filtered and purified by solid-phase cleanup using a polymeric column that
      exhibits reversed-phase and anion-exchange functionalities. OTA was analyzed on a
      narrow-bore reversed-phase C(18) HPLC column with acetonitrile/water (0.1% formic
      acid) (40:60) as mobile phase and quantified with a fluorescence detector. The
      presence of OTA in coffee was confirmed by single-quadruple mass spectrometry
      using an electrospray ionization source. The method has been validated, obtaining
      a recovery of 82.5% and a detection limit of 0.1 ng/g. It has been applied to 20
      coffee samples from various countries and different manufacturers with no
      detection of OTA.

PMID- 14664509
TI  - Effects of coffee components on the response of GABA(A) receptors expressed in
      Xenopus oocytes.
AB  - The effects of both coffee components and coffee extract on the electrical
      responses of GABA(A) receptors expressed in Xenopus oocytes were studied by
      injecting cRNAs of the alpha(1) and beta(1) subunits of the bovine receptors. The
      aqueous extract of coffee dose-dependently inhibited the GABA-elicited responses,
      whereas the lipophilic extract of coffee by diethyl ether slightly potentiated it
      at low doses (0.1-0.4 microL/mL) but showed inhibition at high doses (0.5-0.8
      microL/mL). Theophylline inhibited the response in a noncompetitive mechanism
      (K(i) = 0.55 mM), whereas theobromine and trigonelline hydrochloride inhibited it
      in a competitive manner, K(i) = 3.8 and 13 mM, respectively. Benzothiazole,
      catechol, 2,4-dimethylstyrene, guaiacol, 1-octen-3-ol, sotolone, and 2,3,5
      trimethylphenol potentiated the responses significantly. Potentiation elicited by
      guaiacol and sotolone was independent of GABA concentrations, whereas that by 1
      octen-3-ol was dependent. When 1-octen-3-ol (100 mg/kg) was orally administered
      to mice prior to intraperitoneal administration of pentobarbital, the sleeping
      time of mice induced by pentobarbital increased significantly.

PMID- 14664510
TI  - Antioxidative properties of the essential oil from Pinus mugo.
AB  - The essential oil from Pinus mugo (PMEO) was tested on its antioxidative
      capacity. For this purpose, several biochemical test systems were chosen (e.g.,
      the Fenton System, the xanthine oxidase assay, or the copper-induced oxidation of
      low-density lipoprotein (LDL)). The results show that there is moderate or weak
      antioxidative activity when tested in aqueous environments, like in the Fenton
      system, xanthine oxidase induced superoxide radical formation, or in the HOCl
      driven fragmentation of 1-aminocyclopropane-1-carboxylic acid (ACC). In contrast,
      when tested in more lipophilic environments (e.g., the ACC-cleavage by activated
      neutrophils in whole blood) the PMEO exhibits good antioxidative activity. PMEO
      does also show good antioxidative capacity in another lipophilic test system
      (i.e., the copper induced oxidation of LDL). Some components of PMEO (i.e.,
      Delta(3)-carene, camphene, alpha-pinene, (+)-limonene and terpinolene) were also
      tested. As the PMEO, they showed weak or no antioxidant activity in aqueous
      environments, but some of them were effective antioxidants regarding ACC-cleavage
      by activated neutrophils in whole blood or copper-induced LDL-oxidation.
      Terpinolene, a minor component of PMEO, exhibited remarkable protection against
      LDL-oxidation.

PMID- 14664511
TI  - Inhibitory effect of hot-water extract from dried fruit of Crataegus pinnatifida
      on low-density lipoprotein (LDL) oxidation in cell and cell-free systems.
AB  - The dried fruit of Crataegus pinnatifida, a local soft drink material and medical
      herb, was found to possess potential against oxidative stress. In the preliminary
      study, the antioxidant potential of a hot-water extract obtained from the dried
      fruit of C. pinnatifida (CF-H) was evaluated in terms of its capacity of
      quenching 1,1-diphenyl-2-picrylhydrazyl free radicals (EC(50) = 0.118 mg/mL).
      After content analysis, it was found that CF-H is mainly composed of polyphenols
      including flavonoids (6.9%), procyanidins (2.2%), (+)-catechin (0.5%), and (-)
      epicatechin (0.2%). The antioxidative bioactivity of CF-H had been assess
      previously using the models of CuSO(4) as cell-free system and sodium
      nitroprusside (SNP) plus macrophage RAW 264.7 cells as cell system to induce
      human low-density lipoprotein oxidation. CF-H was found to inhibit relative
      electrophoretic mobility and thiobarbituric acid reactive substances at the
      concentration of 0.5-1.0 mg/mL in the cell-free system and at 0.01-0.10 mg/mL in
      the cell system. Furthermore, it was found that CF-H decreased the SNP-induced
      cell lipid peroxidation and reduced glutathione depletion.

PMID- 14664512
TI  - Chromatographic separation and in vitro activity of sorgoleone congeners from the
      roots of sorghum bicolor.
AB  - Sorgoleone, 2-hydroxy-5-methoxy-3-[(8'Z,11'Z)-8',11',14'-pentadecatriene]-p
      benzoquinone (1), and its corresponding hydroquinone are the major components of
      the root exudate of Sorghum bicolor. The name sorgoleone includes minor analogues
      differing in the length or degree of unsaturation of the 3-alkyl side chain.
      These compounds are known to be phytotoxic, probably through inhibition of
      photosystem II (PSII) driven oxygen evolution, as previously demonstrated for 1.
      Isolation of these sorgoleone congeners was achieved by C(8) column
      chromatography and argentation thin-layer chromatography, and the purified
      compounds were structurally characterized. The abilities of the minor sorgoleones
      to inhibit PSII were similar to that of the major compound, suggesting that all
      of these sorgoleone congeners contribute to the overall allelopathy of sorghum.

PMID- 14664513
TI  - Antifungal activity of some essential oils.
AB  - Thirteen essential oils recovered by steam distillation from Indian herbs were
      analyzed for their chemical compositions using GC and GCMS. The antifungal
      activity against plant and Food mold rot were examined in vitro using poison food
      technique. The essential oil from cymbopogan exhibited control over all the plant
      and food mold rot tested. The bioactive compound in the oil and its minimum
      inhibitory concentration were determined using TLC bioautography.

PMID- 14664514
TI  - Antioxidant activity of knotwood extractives and phenolic compounds of selected
      tree species.
AB  - The antioxidant potency and the radical scavenging capacity of superoxide and
      peroxyl radicals were assessed for 13 hydrophilic knotwood extracts of
      commercially important wood species, or fractions thereof, as well as for five
      pure wood-derived lignans and the flavonoid taxifolin. The chemical composition
      of the knotwood extracts was determined by gas chromatography combined with mass
      spectrometry. Most of the investigated wood species were rich in hydrophilic
      extractives (10-20% of the dry wood) with one or a few compounds dominating in
      each extract. All extracts had a high antioxidative potency and/or radical
      scavenging capacity as compared to the well-known antioxidants Trolox and
      butylated hydroxyanisole. The pure wood-derived lignans and taxifolin also had a
      high antioxidative potency and/or radical scavenging capacity. However, the
      antioxidant potency and/or radical scavenging capacity of several of the
      hydrophilic knotwood extracts were higher than that of the dominating compounds
      in pure form.

PMID- 14664515
TI  - Antifungal clerodane diterpenes from Macaranga monandra (L) Muell. et Arg.
      (Euphorbiaceae).
AB  - Hexane and ethyl acetate phases of the methanol extract of Macaranga monandra
      showed fungal growth inhibition of Colletotrichum acutatum, C. fragariae and C.
      gloeosporioides, Fusarium oxysporum, Botrytis cinerea, Phomopsis obscurans, and
      P. viticola. Bioassay-guided fractionation led to the isolation of two active
      clerodane-type diterpenes that were elucidated by spectroscopic methods (1D-, 2D
      NMR, and MS) as kolavenic acid and 2-oxo-kolavenic acid. A 96-well microbioassay
      revealed that kolavenic acid and 2-oxo-kolavenic acid produced moderate growth
      inhibition in Phomopsis viticola and Botrytis cinerea.

PMID- 14664516
TI  - Isoflavone profile and biological activity of soy bread.
AB  - The present study examines the ability of isoflavone extracts from whole soy
      bread and two soy bread fractions, crumb and crust, to modulate the proliferation
      of human prostate cancer PC-3 cells. Total isoflavone content in the two
      fractions of soy bread were similar (3.17 micromol/g dry basis). However, their
      conjugate patterns were altered. Both fractions of soy bread contained a similar
      level of isoflavone aglycones ( approximately 24%). Low concentrations of soy
      bread extracts increased PC-3 cell proliferation as much as 47% compared to
      untreated control. This proliferative effect in cell growth was reduced at higher
      extract concentration. Soy bread crust extract (10 mg/mL) reduced PC-3 cell
      proliferation by 15% compared to untreated control. Interestingly, wheat bread
      extracts increased cell proliferation at all concentrations tested. Although
      extracts from both breads possessed biological activity, only soy bread crust
      extract reduced PC-3 cell proliferation. This observation may be related to the
      presence of soy in this bread.

PMID- 14664517
TI  - Effects of garlic powders with varying alliin contents on hepatic drug
      metabolizing enzymes in rats.
AB  - The anticarcinogenic effect of garlic has been demonstrated in both epidemiologic
      and experimental studies. In this study, possible mechanisms involved in the
      anticarcinogenic effect of garlic consumption were assessed by determining its
      capacity to alter drug metabolizing enzymes, in relation with its alliin content.
      Rats were fed a diet for 2 weeks containing 5% garlic powders produced from bulbs
      grown on soils with different levels of sulfate fertilization and therefore
      containing differing amounts of alliin. Activities of several hepatic enzymes,
      which are important in carcinogen metabolism such cytochromes P450 (CYP) and
      phase II enzymes, were determined. Garlic consumption slightly increased
      ethoxyresorufin O-deethylase and CYP 1A2 levels. In contrast, garlic consumption
      decreased CYP 2E1 activity and the level of the corresponding isoform. UDP
      glucuronosyl transferase and glutathion S-transferase activities were increased
      by garlic powders. The alliin content of the garlic powders was positively
      correlated with UGT activity although not with other activities. Effects produced
      by garlic consumption were qualitatively similar to that of diallyl disulfide, a
      sulfur compound that has been extensively studied. These data could partially
      explain the chemoprotective effect of garlic.

PMID- 14664518
TI  - Antibacterial action of anacardic acids against methicillin resistant
      Staphylococcus aureus (MRSA).
AB  - The structural and antibacterial activity relationship of 6-alk(en)ylsalicylic
      acids, also known as anacardic acids, was investigated against Gram-positive
      bacteria, emphasizing the methicillin resistant Staphylococcus aureus ATCC 33591
      (MRSA) strain. The unsaturation in the alkyl side chain is not essential in
      eliciting activity but is associated with increasing the activity. The
      antibacterial activity of methicillin against MRSA strains was significantly
      enhanced in combination with C(12:0)-anacardic acid, and the fractional
      inhibitory concentration index for this combination was calculated as 0.281. It
      appears that biophysical disruption of the membrane (surfactant property) is due
      to the primary response to their antibacterial activity, while biochemical
      mechanisms are little involved. The compounds possessing the similar log P values
      exhibit similar activity.

PMID- 14664519
TI  - Emodin isolated from Cassia obtusifolia (Leguminosae) seed shows larvicidal
      activity against three mosquito species.
AB  - Mosquito larvicidal activity of Cassia obtusifolia (Leguminosae) seed-derived
      materials against the fourth-instar larvae of Aedes aegypti, Aedes togoi, and
      Culex pipiens pallens was examined. The chloroform fraction of C. obtusifolia
      extract showed a strong larvicidal activity of 100% mortality at 25 mg/L. The
      biologically active component of C. obtusifolia seeds was characterized as emodin
      by spectroscopic analyses. The LC(50) values of emodin were 1.4, 1.9, and 2.2
      mg/L against C. pipiens pallens, A. aegypti, and A. togoi, respectively.
      Pirimiphos-methyl acts as a positive control directly compared to emodin.
      Pirimiphos-methyl was a much more potent mosquito larvicide than emodin.
      Nonetheless, emodin may be useful as a lead compound and new agent for a
      naturally occurring mosquito larvicidal agent. In tests with
      hydroxyanthraquinones, no activity was observed with alizarin, danthron, and
      quinizarin, but purpurin has an apparent LC(50) value of approximately 19.6 mg/L
      against A. aegypti.

PMID- 14664520
TI  - Phytoestrogens modulate binding response of estrogen receptors alpha and beta to
      the estrogen response element.
AB  - Binding of estrogen receptor (ER) to estrogen response element (ERE) induces gene
      activation and is an important step in estrogen-induced biological effects. Here,
      we investigated the effects of some dietary phytoestrogens such as the
      isoflavones genistein and daidzein, its metabolite equol, and the coumestane
      coumestrol on the binding rate of ERalpha and ERbeta to ERE by a nonradioactive
      real-time method, the Biacore Technology. ERalpha and ERbeta were able to bind to
      ERE immobilized on the surface of a sensor chip even in the absence of estrogens.
      17beta-Estradiol and phytoestrogens induced an increase in ER binding to ERE in a
      concentration-dependent manner. 17beta-Estradiol was a more potent activator of
      binding than the phytoestrogens studied. The concentrations of 17beta-estradiol
      inducing an increase in the binding response of ERalpha and ERbeta to ERE by 50%
      (EC(50)) as compared to unliganded ER were 0.03 and 0.01 microM, respectively.
      Regarding the efficacy of activation of ERalpha, from the most to the least
      effective compound, the sequence and the EC(50) were as follows: 17beta-estradiol
      (0.03 microM) > coumestrol (0.2 microM) > equol (3.5 microM) > genistein (15
      microM) > daidzein (>300 microM) and for ERbeta 17beta-estradiol (0.01 microM) >
      coumestrol (0.025 microM) > genistein (0.03 microM) > daidzein (0.35 microM) >
      equol (0.4 microM). The ratios EC(50)alpha/EC(50)beta were calculated to be for
      17beta-estradiol, 3; coumestrol, 8; equol, 8.8; genistein, 500; daidzein > 850.
      These ratios indicate that genistein and daidzein preferentially activate the
      binding of ERbeta to ERE. The endogenous hormone 17beta-estradiol as well as
      coumestrol and daidzein metabolite equol activate the binding of ERbeta to ERE
      only slightly more effectively than the binding of ERalpha to ERE. Thus, the
      effect of daidzein can be changed from a specific activator of ERbeta to an
      activator of both ER isotypes alpha and beta in humans who are able to convert
      daidzein to equol. While the results of the measurements with ERalpha were in
      line with the binding affinities of compounds tested for ER, there was a distinct
      difference between our results and the binding affinities of phytoestrogens for
      the ERbeta. This leads to the conclusion that phytoestrogens differ not only in
      their binding affinities for the ER, but also in their potential to increase the
      rate of receptor binding to the ERE.

PMID- 14664521
TI  - Antioxidizing potency of phenol compounds in olive oil mill wastewater.
AB  - The antioxidizing potency of phenol compounds contained in olive oil mill
      wastewater (OOMWW) has been elucidated. Commercially available phenol standards
      at varying concentrations and the Rancimat oxidation test have been used. Refined
      purified olive oil was utilized as an oxidation lipid substrate. Synthetic
      antioxidants, such as 2,3-tert-butyl-4-hydroxyanisole (BHA), 3,5-di-tert-butyl-4
      hydroxytoluene (BHT), l-ascorbic acid, and gallates (commonly used as food
      preservatives), and other known chemicals endowed with antioxidizing properties
      have been employed as reference compounds. The OOMWW phenol compounds have been
      classified into different groups depending on their antioxidizing potency. This
      was significantly affected by the tested concentrations of the standards.
      Mixtures of phenol standards and other antioxidants (l-proline, chlorophyll a,
      chlorophyll b, and alpha-, gamma-, and delta-tocopherol) have also been tested.
      Many phenol compounds present in OOMWW showed antioxidizing potency higher
      compared to that of the less safe synthetic antioxidants and could therefore
      replace these in the industrial preservation of food items. They could also be
      used in combination with other natural antioxidants (e.g., tocopherols). In fact,
      some mixtures of antioxidants, owing also to the synergistic phenomena, showed
      strong antioxidizing potency.

PMID- 14664522
TI  - Alkaloids from the poisonous plant Ipomoea carnea: effects on intracellular
      lysosomal glycosidase activities in human lymphoblast cultures.
AB  - There is natural intoxication of livestock by the ingestion of Ipomoea carnea
      (Convolvulaceae) in Brazil and other parts of the world. The alkaloidal
      glycosidase inhibitors swainsonine, 2-epi-lentiginosine, and calystegines B(1),
      B(2), B(3), and C(1) have been identified as constituents of this plant.
      Swainsonine is a potent inhibitor of rat lysosomal alpha-mannosidase, with an
      IC(50) value of 0.02 microM, whereas calystegines B(1), B(2), and C(1) are potent
      inhibitors of rat lysosomal beta-glucosidase, with IC(50) values of 2.1, 0.75,
      and 0.84 microM, respectively. The action of swainsonine results in a lysosomal
      storage disorder that closely mimics alpha-mannosidosis in humans. To determine
      whether the toxicity of I. carnea to livestock is due to purely swainsonine or
      due to a combination of effects by swainsonine and calystegines, intracellular
      lysosomal glycosidase activities in normal human lymphoblasts grown with
      inhibitors in the medium were examined. Incubation of lymphoblasts with 0.1
      microM swainsonine for 3 days resulted in approximately 60% reduction of alpha
      mannosidase activity. On the other hand, calystegines B(2) and C(1) showed no
      inhibition of beta-glucosidase up to 1 mM; instead inclusion of calystegines B(2)
      and C(1) at 100 microM in the culture medium increased its activity by 1.5- and
      1.6-fold, respectively. Calystegines B(2) and C(1) seem to act as chemical
      chaperones, enhancing correct folding of the enzyme and enabling smooth
      trafficking to the lysosome. The lysosomal beta-glucosidase inhibitory
      calystegines seem to have little risk of inducing intoxication of livestock.

PMID- 14664523
TI  - Development and characterization of biodegradable films made from wheat gluten
      protein fractions.
AB  - Gliadins and glutenins were extracted from commercial wheat gluten on the basis
      of their extractability in ethanol and used to produce film-forming solutions.
      Films cast using these gliadin- and glutenin-rich solutions were characterized.
      Glycerol was used as a plasticizer, and its effect on the films was also studied.
      Films obtained from the glutenin fraction presented higher tensile strength
      values and lower elongation at break and water vapor permeability values than
      gliadin films. Gliadin films disintegrated when immersed in water. The GAB
      isotherm model was used to describe the equilibrium moisture sorption of the
      films. The glycerol concentration largely modified mechanical and water vapor
      barrier properties of both film types.

PMID- 14664524
TI  - Identification of species-specific DNA in feedstuffs.
AB  - Due to the menace of transmission of spongiform encephalopathies, feed components
      intended for ruminant nutrition must be checked for the presence of ruminant
      derived materials. A sensitive method for the identification of bovine- and ovine
      and also swine- and chicken-specific mitochondrial DNA sequences based on
      Polymerase Chain Reaction (PCR) has been developed. The specificity of the
      primers for PCR has been tested using samples of DNA of other vertebrate species,
      which may also be present in rendering plant products intended for feed
      manufacture. The method allows the detection in concentrate mixtures of 0.01% of
      the target species derived material. The identity of a sample containing 0.1% of
      bovine, ovine, swine, and chicken meat-and-bone meal has further been confirmed
      by sequencing.

PMID- 14664525
TI  - Comparison of physicochemical, binding, and antibacterial properties of chitosans
      prepared without and with deproteinization process.
AB  - Physicochemical, binding, and antibacterial properties of chitosans prepared
      without and with deproteinization (DP) process (5, 10, 15, and 30 min at 15
      psi/121 degrees C) were compared. Chitosan from DP 0 min had comparable nitrogen
      content, lower degree of deacetylation and solubility, but higher molecular
      weight and viscosity than chitosans from DP 5-30 min. The latter four chitosans
      showed differences only in molecular weight. Deproteinization treatment resulted
      in slightly decreased L values and increased a and b values compared with those
      of DP 0 min. Chitosan from DP 0 min had comparable water and fat-binding capacity
      (FBC) except for chitosan from DP 15 min, which had a higher FBC but lower dye
      binding capacity than those of the four chitosans from DP 5-30 min. The
      antibacterial activities of chitosans against seven different bacteria showed
      that the inhibitory effects varied with the deproteinization time and the
      particular bacterium.

PMID- 14664526
TI  - Purification and characterization of proteases from Bacillus amyloliquefaciens
      isolated from traditional soybean fermentation starter.
AB  - Bacillus amyloliquefaciens FSE-68 isolated from meju, a Korean soybean
      fermentation starter, was identified on the basis of biophysical tests and 16S
      rRNA gene sequence. A neutral metalloprotease (NPR68) and an alkaline serine
      protease (APR68) were purified by ammonium sulfate precipitation and cation
      exchange chromatography and identified on the basis of their activities at
      different pH values and the selective protease inhibitors. The molecular weights
      of NPR68 and APR68 measured with ESI-MS were 32743 (+/- 0.8) and 27443 (+/- 0.5)
      Da, respectively. Against oxidized insulin chains, the NPR68 has a cleavage
      preference at the site where leucine is located as a P1' residue followed by
      phenylalanine, and the APR68 has broad specificity and favors leucine at the P1
      site. These results indicate that the proteases are natural variants of
      subtilisin and bacillolysin.

PMID- 14664527
TI  - Volatile compounds in a spanish red wine aged in barrels made of Spanish, French,
      and American oak wood.
AB  - A red Rioja wine was aged in barrels made of Spanish oak wood (Quercus robur,
      Quercus petraea,Quercus pyrenaica, and Quercus faginea) during 21 months. The
      concentrations of some volatile compounds [syringaldehyde, vanillin, eugenol,
      maltol, guaiacol, 4-ethylphenol, cis and trans isomers of beta-methyl-gamma
      octalactone, 2-furfuraldehyde, 5-methyl-2-furfuraldehyde, 5-(hydroxymethyl)-2
      furfuraldehyde, and furfuryl alcohol] were studied in these wines and compared
      with those of the same wine aged in barrels made from French oak of Q. robur
      (Limousin, France) and Q. petraea (Allier, France) and American oak of Quercus
      alba (Missouri). Similar concentrations of these compounds were found in wines
      aged in Spanish and French oak wood barrels, and significantly different
      concentrations were found with respect to wines aged in barrels made of American
      oak wood, indicating a different behavior. Thus, wines with different
      characteristics were obtained, depending on the kind of wood. Also, the kind of
      wood had an important influence on sensory characteristics of wine during the
      aging process. Spanish oak wood from Q. robur, Q. petraea, and Q. pyrenaica can
      be considered to be suitable for barrel production for quality wines, because a
      wine aged in barrels made of these Spanish oak woods showed similar and
      intermediate characteristics to those of the same wine aged in French and
      American oak woods usually used in cooperage.

PMID- 14664528
TI  - Stimulation of nicotine demethylation by NaHCO(3) treatment using greenhouse
      grown burley tobacco.
AB  - Experiments were conducted in tobacco (Nicotiana tabacum L.) to investigate the
      effect of sodium bicarbonate (NaHCO(3)) on the conversion of nicotine to
      nornicotine, a secondary alkaloid that can form the tobacco-specific nitrosamine
      N-nitrosonornicotine (NNN). The results showed that, under optimum conditions,
      NaHCO(3) stimulated nicotine conversion in converter plants to the maximum level
      predetermined by the genetic background. The conversion level in NaHCO(3)-treated
      leaves was 2-3 times higher than that in control leaves. For young seedlings the
      optimum concentration of sodium bicarbonate was 0.8% aqueous solution, and for
      adult plants the optimum concentration was 1%. Lower concentrations resulted in
      partial stimulation, whereas higher concentration damaged leaf tissue and
      resulted in a lower conversion level. Studies with different temperatures (from
      22 to 43 degrees C) showed that 37 degrees C was optimal. This temperature
      allowed the least amount of time, 2-3 days for mature leaves and 4-6 days for
      green leaves, for the major converters to reach >95% of nicotine conversion. An
      examination of leaves from different growth stages and stalk positions showed
      that the amount of time needed for conversion was longer for young leaves and
      shorter for mature leaves. Treatment of leaves with NaHCO(3) affords a rapid and
      convenient means of identifying and removing nornicotine converter plants during
      growth in the greenhouse or field.

PMID- 14664529
TI  - Chemical and nutritional characteristics of United States soybeans and soybean
      meals.
AB  - Two experiments were conducted to determine U.S. soybean meal (SBM) variation. In
      experiment 1, SBM from 55 U.S. processors was evaluated. Significant (P < 0.05)
      but numerically small differences were detected in dry matter (DM) and organic
      matter (OM) concentrations. Crude protein (CP) concentrations (51.6-54.6%) were
      higher (P < 0.05) in SBM produced in the southern U.S. Lipid and total dietary
      fiber concentrations also differed (P < 0.05). The protein dispersibility index
      was affected (P < 0.05) by the source of SBM. In experiment 2, soybeans and
      resultant SBMs were obtained from 10 U.S. processing plants. Soybean DM, OM, and
      CP concentrations differed (P < 0.05). Soybean meal varied (P < 0.05) in CP (48.2
      56.2%), acid-hydrolyzed fat (3.3-9.2%), total dietary fiber (17.0-20.7%), and
      lysine concentrations. Soybean meal carbohydrate composition was also affected by
      processing conditions. These results indicate a significant variation in chemical
      and nutritional characteristics of U.S. SBM from different sources.

PMID- 14664530
TI  - Cholesterol content in meat of some poultry and fish species as influenced by
      live weight and total lipid content.
AB  - Total cholesterol content in 24 fillets (F) of males and females of common carp,
      35 samples of male chicken breast meat (BM) and thigh meat (TM), and 48 samples
      of male turkey BM and TM, respectively, was determined by high-performance liquid
      chromatography after total lipid (TL) extraction using n-hexane/2-propanol
      mixture. Cholesterol content in male carp fillets (77.6 mg/100 g) was higher (P <
      0.001) in comparison with females (69.4 mg/100 g). Irrespective of the sex
      differences, cholesterol content increased (P < 0.01) in the sequence chicken BM
      (53.0 mg/100 g) = turkey BM (53.0) < turkey TM (61.5) < carp F (73.5) < chicken
      TM (82.9 mg/100 g). Cholesterol content in chicken TM decreased (P < 0.05) with
      increasing live weight reached at the age of 43 days, but did not change (P >
      0.05) in other tested tissues. Cholesterol concentration in TL of all five tested
      tissues within three animal species decreased sharply (P < 0.001) with increasing
      TL content reached in a given tissue at the fixed age. It follows from the
      results of the study that a two hundred gram portion of carp F and chicken TM
      without skin represents 49 and 55% of the upper limit of daily cholesterol
      intake, respectively.

PMID- 14664531
TI  - Determination of sterol and fatty acid compositions, oxidative stability, and
      nutritional value of six walnut (Juglans regia L.) cultivars grown in Portugal.
AB  - Six cultivars (Franquette, Marbot, Mayette, Mellanaise, Lara, and Parisienne) of
      walnuts (Juglans regia L.) were collected during the 2001 crop, from Braganca,
      Portugal. Chemical composition, including moisture, total oil content, crude
      protein, ash, carbohydrates, and nutritional value, was evaluated. Fat was the
      predominant component, ranging from 62.3 to 66.5%. Total oil was extracted and
      analyzed for fatty acids, sterols, oxidative stability, and peroxide value. Fatty
      acids and sterols were determined by gas-liquid chromatography coupled to a flame
      ionization detector. Eighteen fatty acids were quantified. Polyunsaturated fatty
      acids and, in particular, linoleic acid were predominant. Beta-Sitosterol,
      delta(5)-avenasterol, and campesterol were the major sterols found. Differences
      were observed among the studied cultivars, especially in peroxide values and in
      the sterol profile.

PMID- 14664532
TI  - Feasibility study on the use of visible and near-infrared spectroscopy together
      with chemometrics to discriminate between commercial white wines of different
      varietal origins.
AB  - The use of visible (vis) and near-infrared spectroscopy (NIR) was explored as a
      tool to discriminate between samples of Australian commercial white wines of
      different varietal origins (Chardonnay and Riesling). Discriminant models were
      developed using principal component analysis (PCA), principal component
      regression (PCR), and discriminant partial least-squares (DPLS) regression. The
      samples were randomly split into two sets, one used as a calibration set (n =
      136) and the remaining samples as a validation set (n = 133). When used to
      predict the variety of the validation set samples, the DPLS models correctly
      classified 100% of Riesling and up to 96% of Chardonnay wines. These results
      showed that vis-NIR might be a suitable and alternative technology that can be
      easily implemented by the wine industry to discriminate Riesling and Chardonnay
      commercial wine varieties. However, the relatively limited number of samples and
      varieties involved in the present work suggests caution in extending the
      potential of such a technique to other wine varieties.

PMID- 14664533
TI  - Comparison of static headspace, headspace solid phase microextraction, headspace
      sorptive extraction, and direct thermal desorption techniques on chemical
      composition of French olive oils.
AB  - Static headspace (SHS), headspace solid phase microextraction (HS-SPME),
      headspace sorptive extraction (HSSE), and direct thermal desorption (DTD) were
      applied to the analysis of four French virgin olive oils from Corsica. More than
      60 compounds were isolated and characterized by GC-RI and GC-MS. SHS was not
      suited to the characterization of olive oil volatile compounds because of low
      sensitivity. The SPME and HSSE techniques were successfully applied to olive oil
      headspace analysis. Both methods allow the characterization of volatile compounds
      (mainly C(6) aldehydes and alcohols), which contribute significantly to the
      "green" flavor note of virgin olive oils. The PDMS stir bar showed a higher
      concentration capacity than a DVB/CAR/PDMS SPME fiber due to the higher volume of
      polymeric coating. DTD was a very good tool for extracting volatile and
      especially semivolatile compounds, such as sesquiterpenes, but requires a
      significant investment like that for HSSE. Finally, SPME may be a more
      appropriate technique for routine quality control due to its operational
      simplicity, repeatability, and low cost.

PMID- 14664534
TI  - Flazasulfuron: alcoholysis, chemical hydrolysis, and degradation on various
      minerals.
AB  - The herbicide flazasulfuron undergoes rapid alcoholysis. High yields of the
      corresponding carbamate and aminopyrimidine are obtained after the alcoholysis
      process (methanol or ethanol) at 30 degrees C, in the course of which the
      concomitant rearrangement reaction remains minor. Hydrolysis (pH ranging from 5
      to 11) of flazasulfuron at 30 degrees C principally involves the rearrangement
      into urea after elimination of SO(2) and can lead, in a small proportion, to both
      aminopyrimidine and pyridinesulfonamide. First-order kinetics correctly describes
      the rates of alcoholysis and hydrolysis. The sulfonylurea-bridge contraction and
      final transformation into the correspondent amine were evaluated with a first
      order kinetics hypothesis. Transformations in amine and urea in aqueous medium
      are pH dependent. The chemical degradation of flazasulfuron on various dry
      minerals (calcium bentonite, kaolinite, silica, montmorillonite, and alumina) was
      investigated at 30 degrees C. The rearrangement reaction is the only one observed
      in the presence of kaolinite and alumina. However, hydrolysis and rearrangement
      have the same reaction rate in the presence of silica. The hydrolysis paths of
      flazasulfuron are comparable to the ones described for rimsulfuron.

PMID- 14664535
TI  - Perylenequinones act as broad-spectrum fungicides by generating reactive oxygen
      species both in the dark and in the light.
AB  - Natural perylenequinonoid pigments (PQPs) have long been known as excellent
      photosensitizers. Here it is reported that PQPs, when dispersed into a micellar
      system, are unexpectedly very effective in inhibiting the growth of various fungi
      in the dark and that light can enhance the activity further. In both cases,
      reactive oxygen species (ROS) play a crucial role. The unique ROS-based
      antifungal mechanism and the excellent physicochemical properties of PQPs promise
      the advent of a new generation of wide-spectrum agrofungicides.

PMID- 14664536
TI  - Bioconcentration and elimination of sulfamethazine and its main metabolite in
      sturgeon (Acipenser schrenkii).
AB  - A steady-state bioconcentration and elimination of sulfamethazine (SM(2)) in the
      sturgeon (A. schrenkii) was conducted in flow-through aqueous conditions. Two
      treated groups of fish were exposed to concentrations of 1.00 and 0.10 mg/L of
      SM(2), respectively. SM(2) and its main metabolite, N(4)-acetyl-SM(2), were
      determined in both fish muscle and water during the 8-day uptake period and the
      subsequent 6-day elimination period. Rapid uptakes of the drug were observed in
      both treated groups. Muscle tissue residues plateaued after approximately 3 days.
      The bioconcentration factor in muscle (BCF(m)) in the low-concentration drug
      solution was 1.19 and that in the high-concentration-treated level was 0.61. The
      calculated biodegradation index was 3.72%. The elimination half-times (t(1/2)) of
      the two treatment levels were 19.44 and 23.52 h, respectively. The result
      indicates that SM(2) will neither bioconcentrate in individual aquatic organisms
      nor biomagnify in the food chain, although the BCF(m) was relatively higher under
      the low-concentration exposure.

PMID- 14664537
TI  - Clay-catalyzed nitration of a carbamate fungicide diethofencarb.
AB  - The unique nitration of the carbamate fungicide diethofencarb (Powmyl, isopropyl
      3,4-diethoxycarbanilate) was examined in 14 Japanese soils and three types of
      clays under the aerobic conditions using the (14)C-labeled compound. Nitration at
      the 6-position of the 3,4-diethoxyphenyl ring was a clay-catalyzed reaction and
      extremely enhanced under the dry conditions. Kinetic and product analysis on
      nitration of nine (14)C-labeled carbamate analogues in the kaolinite thin layer
      showed the nitration proceeding electrophilically. Requirement of molecular
      oxygen and retardation of nitration by radical scavengers and spin-trap reagents
      together with semiempirical AM1 molecular orbital calculations strongly suggested
      contribution of a radical mechanism, and these different speculations on the
      reaction mechanism might originate from the heterogeneous reaction environment on
      clay.

PMID- 14664538
TI  - Study of aged cognac using solid-phase microextraction and partial least-squares
      regression.
AB  - Headspace solid-phase microextraction (SPME) and GC-MS were used to analyze 17
      commercial French Cognac brandies (9 young and 8 well-aged, ranging in age from 3
      to 55 years). Sixty-four volatiles were chosen on the basis of chromatographic
      separation and/or known odor importance. Chromatographic peaks were manually
      integrated and the peak area data analyzed using partial least-squares (PLS)
      regression to study relationships between volatile composition (X variables) and
      age (Y variable). When only those compounds with the highest significance were
      included and from these selected the variables (a total of 33) with the highest
      correlation loadings on the first two principal components, principal component 1
      explained 82% of the variance of the measured compounds and 85% of the variance
      in age. These were considered the most important volatiles to distinguish
      products of different ages because young and old samples were separated along
      principal component 1. Norisoprenoids, terpenes, and acetate esters had weaker
      positive and negative loadings and were therefore left out. The PLS model could
      predict sample age accurately with the optimum 33 volatiles as well as with a
      smaller subset consisting of ethyl esters and methyl ketones.

PMID- 14664539
TI  - Role of the soluble and micelle-bound heat-induced protein aggregates on network
      formation in acid skim milk gels.
AB  - Gel formation was monitored by low amplitude rheometry during acidification at 40
      degrees C with 1.5% glucono-delta-lactone in combined milk systems containing
      soluble and/or micelle-bound heat-induced (95 degrees C/10 min) aggregates of
      denatured whey proteins and kappa-casein and in heated dairy mixes with varying
      micellar casein/whey protein ratio (CN/WP). Both soluble and micelle-bound
      aggregates increased gelation pH and gel strength. Micelle-bound aggregates
      seemed to modify the micelle surface so that micelles were destabilized at a pH
      of 5.1 (instead of 4.7), while soluble aggregates precipitated at their
      calculated pI of approximately 5.3, and initiated an early gelation by
      interacting with the micelles. Decreasing the CN/WP ratio produced larger
      aggregates with higher whey protein: kappa-casein ratio, which gave more elastic
      gels. The specific effects of the micellar and soluble aggregates on gel strength
      are discussed with respect to their relative proportions in the heated milk.

PMID- 14664540
TI  - Influence of nitrogen fertilizers on the yield and composition of thyme (Thymus
      vulgaris).
AB  - The influence of nitrogen fertilizers on the yield of crop, as well as on the
      production and composition of the essential oil and some other chemical
      characteristics of thyme, was investigated. Different levels of fertilizers (N =
      0, 45, 90, and 135 kg x ha(-)(1)) were applied. It was found that fertilizers
      increase thyme crop, but differences in the yield of essential oil were not
      remarkable. However, the use of certain amounts of nitrogen fertilizers resulted
      in higher yields of essential oil obtainable from the cultivation area unit
      (dm(3) ha(-)(1)). Totally, 61 constituents were identified in thyme essential oil
      by capillary GC and GC-MS. Thymol was the dominating compound in the all analyzed
      oils (44.4-58.1%), followed by p-cymene (9.1-18.5%), gamma-terpinene (6.9-18.9%),
      and carvacrol (2.4-4.2%). Differences in the percentage of these and other
      compounds in thyme herb cultivated under different fertilization doses were not
      significant; very slight changes in the percentage composition were detected
      after drying. Some variations in the amount of individual constituents expressed
      in arbitrary units per kilogram of herb (which is almost equivalent to mg x kg(
      )(1)) were observed. The highest amounts of sugars and sucrose, in particular,
      were determined in the second year of thyme cultivation. Differences in the
      content of dry soluble substances were not meaningful, and there was no effect of
      nitrogen fertilizers on this chemical characteristic. Some effect of
      fertilization on the content of vitamin C and carotenes was observed in the first
      year of thyme cultivation. It was determined that nitrogen fertilizers influence
      the amount of nitrates, which was highest in the second-year-first-harvest.

PMID- 14664541
TI  - (E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene: a potent grape-derived odorant in
      wine.
AB  - (E)-1-(2,3,6-Trimethylphenyl)buta-1,3-diene (TPB) was identified as a potent
      odorant in acid hydrolysates of crude glycoconjugate fractions isolated from
      grapes and grape vine leaves. TPB was also identified in a Semillon wine, using
      gas chromatography/mass spectrometry, by co-injection with an authentic sample.
      TPB had an aroma detection threshold of 40 ng/L in a neutral white wine and the
      concentration of TPB in four out of five white wines analyzed ranged from 50 to
      210 ng/L.

PMID- 14664542
TI  - Tyrosinase inhibitory activity of cucumber compounds: enzymes responsible for
      browning in cucumber.
AB  - The inhibition of mushroom tyrosinase by cucumber extracts was evaluated. The
      inhibitory effect was measured by both polarographic and spectrophotometric
      methods. The commercial aldehyde, trans,cis-2,6-nonadienal, described as a major
      volatile compound of cucumber, was characterized as a noncompetitive inhibitor
      against 4-tert-butylcatechol oxidation by mushroom tyrosinase. The K(I) obtained
      was 3.4 mM. Polyphenol oxidase (PPO) activity was not detected in cucumber skin
      extracts. However, the presence of PPO was revealed by Western blot; a single
      band was found with a M(r) of 53 kDa. These results support the assumption that
      the enzyme PPO is present in the cucumber skin, but its activity is inhibited.
      Peroxidase (PO) was also found in cucumber skin extracts. This enzyme was
      detected in the soluble fraction but not in the membrane fraction. The kinetic
      characterization of PO was carried out. Native isoelectric focusing revealed
      several acidic PO isoenzymes with a pI in the range between 5 and 6, a basic
      isoenzyme, and one principal neutral isoenzyme of pI = 7.2.

PMID- 14664543
TI  - Microencapsulated iron for milk fortification.
AB  - This study was designed to develop a microencapsulated iron that could be used to
      fortify milk and to determine the sensory properties of milk fortified with
      microencapsulated iron. Coating material was polyglycerol monostearate (PGMS),
      and selected core material was ferric ammonium sulfate. The highest efficiency of
      microencapsulation was 75% with 5:1:30 ratio (w/w/v) as coating to core materials
      to distilled water. Iron release was 12% when stored at 4 degrees C for 3 days.
      The TBA value was the lowest when 100 ppm of capsulated iron was added into milk
      and was significantly lower in capsulated groups compared with that in
      uncapsulated groups. In an in vitro study, only 3-5% of iron was released in
      simulated gastric fluid (pH 3, 4, 5, and 6). Comparatively, iron release
      increased dramatically from 12.3% (pH 5) to 95.7% (pH 8) for 60 min of incubation
      in simulated intestinal fluid. In a sensory analysis, most aspects except for
      metallic taste and color were not significantly different between control and
      capsulated iron fortified milk at 3 days of storage. However, between capsulated
      and uncapsulated groups, astringency, metallic, color, and overall scores were
      significantly different. The present study indicated that the use of
      microencapsulated iron with PGMS is effective for fortifying milk.

PMID- 14664544
TI  - Effects of alpha-, gamma-, and delta-tocopherols on the autoxidation of purified
      rapeseed oil triacylglycerols in a system containing low oxygen.
AB  - Controversial data on the antioxidant effects of tocopherols have already been
      shown in different test systems, yet delta-tocopherol was hardly considered. This
      study was designed to assess the effects and degradation of alpha-, gamma-, and
      delta-tocopherol in four concentrations from between 0.01 and 0.25% on the
      oxidation of purified rapeseed oil trigacylglycerols (RO-TAG) at 40 degrees C in
      the dark in a low oxygen containing system for 11 weeks. Oxidation experiments
      were performed weekly by assessing primary (peroxide value, PV; conjugated
      dienes, CD) and secondary (p-anisidine reactive products, p-AV; hexanal)
      oxidation products, the degree of unsaturation with the iodine value (IV), and
      the stability of tocopherols. Test approaches were performed with and without the
      addition of 0.01% alpha,alpha'-azoisobutyronitrile (AIBN), which is a known
      radical initiator. alpha- and gamma-Tocopherols increased the rate of lipid
      oxidation, which was more pronounced in the presence of AIBN. Only the lowest
      amount of 0.01% gamma-tocopherol was comparable to the control sample in the test
      without AIBN. The most effective was shown to be delta-tocopherol, which did not
      elevate lipid oxidation except the PV in the AIBN test, but they did not delay it
      either. delta-Tocopherol was the most stable followed by gamma- and alpha
      tocopherol. For alpha- and gamma-tocopherol, but not for delta-tocopherol, strong
      correlations were found between the tocopherol degradation and the extent of
      oxidation. Results suggest that (i). at concentrations higher than 0.05%,
      tocopherols are less efficient and turn their mode of action or participate in
      side reactions in RO-TAG and (ii). delta-tocopherol was shown to be the most
      stable and effective under these low oxygen conditions.

PMID- 14664545
TI  - Kinetic study of the oxidation of quercetin by mushroom tyrosinase.
AB  - The kinetic behavior of mushroom tyrosinase in the presence of the flavonol
      quercetin was studied. This flavonol was oxidized by mushroom tyrosinase and the
      reaction was followed by recording spectral changes over time. The spectra
      obtained during the reaction showed two isosbectic points, indicating a stable o
      quinone. When quercetin was oxidized by tyrosinase in the presence of cysteine
      and 3-methyl-2-benzothiazolone hydrazone (Besthorn's hydrazone, MBTH) isosbestic
      points were also observed indicating a definite stoichiometry. From the data
      analysis of the initial rate in the presence of MBTH, the kinetic parameters: =
      (16.2 +/- 0.6) microM/min, = (0.12 +/- 0.01) mM, (/) = (V(max)/K(S)(')()) = (13.5
      +/- 1.4) x 10(-)(2) min(-)(1), = (6.2 +/- 0.6) s(-)(1) were determined. We
      propose that quercetin acts simultaneously as a substrate and a rapid reversible
      inhibitor of mushroom tyrosinase, depending on how it binds to the copper atom of
      the enzyme active site. Thus, if the binding occurs through the hydroxylic groups
      at the C3' and C4' positions, quercetin acts as a substrate, while if it occurs
      through the hydroxylic group at the C3 position of the pyrone ring, quercetin
      acts as an inhibitor.

PMID- 14664546
TI  - Evaluation of antioxidant potential of aloe vera (Aloe barbadensis miller)
      extracts.
AB  - The polysaccharide and flavonoid concentrations of two-, three-, and four-year
      old Aloe vera were determined, and their antioxidant activities were evaluated
      compared to BHT and alpha-tocopherol by the DPPH radical scavenging method and
      the linoleic acid system at 100 microg of soluble solids per mL of ethanol. The
      results showed that three-year-old Aloe vera contained significantly higher
      levels of polysaccharides and flavonoids than two- and four-year-old Aloe vera,
      and no significant differences in flavonoid levels were found between three- and
      four-year-old Aloe vera. All the aloe extracts showed significant antioxidant
      activity. The antioxidant activity of Aloe vera extracts and reference compounds
      followed the order: three-year-old Aloe vera > BHT > four-year-old Aloe vera >
      alpha-tocopherol > two-year-old Aloe vera. The three-year-old extract exhibited
      the strongest radical scavenging activity of 72.19%, which is significantly
      higher than that of BHT at 70.52% and alpha-tocopherol at 65.20%. These data
      suggest that the growth stage plays a vital role in the composition and
      antioxidant activity of Aloe vera.

PMID- 14664547
TI  - Modeling protein functional properties from amino acid composition.
AB  - Physicochemical and functional properties of proteins were modeled as a function
      of the contributions of each of the 20 coded amino acids to three (z-scores) or
      five (extended z-scores) amino acid principal properties using partial least
      squares regression. The five term models were in all cases stronger in both fit
      and prediction than the three term models, indicating that useful information is
      contained in the fourth and fifth property scores. Models predicting protein
      hydrophobicity (R = 0.932), viscosity (R = 0.737), and foam capacity (R = 0.880)
      from amino acid composition rather than sequence were obtained. It is likely that
      additional functional and physicochemical properties of proteins can be modeled
      in this way.

PMID- 14664548
TI  - Identification and differences of total proteins and their soluble fractions in
      some pseudocereals based on electrophoretic patterns.
AB  - Genetic diversity and relationships of 11 species and cultivars belonging to
      different Angiosperms families were examined using sodium dodecyl sulfate seed
      protein markers. The protein was resolved into 36 bands (for soybean), 41 (for
      quinoa), 35 (for buckwheat), and 28 to 39 bands of Amaranth species,
      respectively. All species and cultivars can be distinguished from each other.
      Soybean, quinoa, and buckwheat species had a characteristic protein pattern
      showing a high degree of polymorphism. The protein patterns of soybean were
      considerably different from other species. Amaranth species had similar seed
      protein electrophoretic profile. The similarity coefficients calculated on the
      basis of presence and absence of bands ranged from 0.08 to 0.97. Following the
      UPGMA algorithm of similarity coefficients, the examined species and varieties
      could be clustered into two similarity groups. Our results did not confirm the
      Tachtadzjan hypothesis that Polygonales (e.g., buckwheat) and Caryophyllales
      (e.g., quinoa and amaranth) are closely related. Our data rather indicate
      occurrence of significant genetic distance (similarity coefficients 0.05-0.10).
      Also, it is doubtful that amaranth and quinoa species are also closely related
      (similarity coefficients varied from 0.16 to 0.25). It seems that soybean,
      quinoa, buckwheat, and amaranth (as a genus) can be considered as phylogenetic
      distant taxa. Differences and similarities in the secondary structure were
      observed by circular dichroism spectra. Some similarity was found between these
      plants in their soluble protein fractions and amino acid composition. These
      plants can be a substitution of each other as well as for cereals.

PMID- 14664549
TI  - Solubilization of water soluble anthocyanins in apolar medium using reverse
      micelle.
AB  - Crude anthocyanins extracted from grape skin were solubilized in hexane
      containing 100 mM bis(2-ethylhexyl)sodium sulfosuccinate (AOT) by forming stable
      reverse micelles (RMs). Anthocyanins solubilized in RMs showed about four times
      greater color intensity than that in aqueous medium. The color intensity of
      anthocyanins in RMs was primarily affected by the interaction between sulfonate
      head of AOT and flavylium cation of anthocyanins. The molar ratio of water to AOT
      (Wo) also influenced the color properties. As the Wo increased from five to 20,
      the color intensity increased and resulted in a bathochromic shift. This result
      suggests that increased micelle size facilitates complexation between AOT and
      flavylium cation. The color stability of anthocyanins in RM was higher than that
      of buffered anthocyanins during the storage at 30 degrees C. The current study
      might be utilized as a model system to predict color properties of anthocyanins
      in apolar medium.

PMID- 14664550
TI  - Effect of different dextrose equivalent of maltodextrin on the interactions with
      anionic surfactant in an isothermal titration calorimetry study.
AB  - Isothermal titration calorimetry (ITC) was used to study interactions between an
      anionic surfactant (sodium dodecyl sulfate, SDS) and maltodextrins with different
      dextrose equivalents (DE) in a buffer solution (pH 7.0, 10 mM NaCl, 20 mM Trizma,
      30.0 degrees C). The interaction between SDS and maltodextrin was exothermic,
      which was attributed to incorporation of the hydrocarbon tail of the surfactant
      into a helical coil formed by the maltodextrin molecules. ITC measurements
      indicated that the number of SDS molecules bound per gram of maltodextrin
      increased with decreasing maltodextrin DE, i.e., increasing molecular weight. It
      was proposed that SDS only binds to maltodextrin molecules that have a DE greater
      than 10 glucose units.

PMID- 14664551
TI  - Effect of illumination with the visible polarized and nonpolarized light on alpha
      amylolysis of starches of different botanical origin.
AB  - The alpha-amylolysis of potato, corn, waxy corn, and amaranthus starches with
      porcine pancreatic alpha-amylase upon illumination with visible polarized and
      nonpolarized light was studied. Samples were illuminated for 1 h either directly
      after blending the enzyme with starch or the enzyme solutions were illuminated
      for 1 h prior to the admixture of starch. Independently of the mode of
      illumination, no significant change in the hydrolysis kinetics was noted for
      corn, waxy corn, and amaranthus starches. The illumination of potato starch in
      the presence of alpha-amylase with polarized and nonpolarized light significantly
      accelerated the hydrolysis. In the first 5-h step the hydrolysis rate increased
      from 12.0 to 60.0 g x kg(-)(1) h(-)(1). Preillumination of enzyme in solution
      resulted in an increase in the rate of hydrolysis to 151.6 and 131.4 g x kg(-)(1)
      h(-)(1) after illumination with polarized and nonpolarized light, respectively.
      Circular dichroism spectra of alpha-amylase solutions stored in the dark and
      illuminated with visible polarized and nonpolarized light provided evaluation of
      the protein conformation, whereas exposure of enzyme solutions to the
      nonpolarized did not change the secondary structure of the protein. The
      illumination of the alpha-amylase solutions with polarized light significantly
      changed the amounts of alpha-helix and beta-form vs unilluminated samples: 42.3%
      and 25.5% vs 36.6% and 30.2%, respectively.

PMID- 14664552
TI  - Combined impact of pH and organic acids on iron uptake by Caco-2 cells.
AB  - Previous studies have shown that organic acids have an impact on both Fe(II) and
      Fe(III) uptake in Caco-2 cell. However, to what extent this effect is correlated
      with the anion of organic acids per se, or with the resulting decrease in pH, has
      not yet been clarified. Therefore, we studied the effect of five organic acids
      (tartaric, succinic, citric, oxalic, and propionic acid) on the absorption of
      Fe(II) and Fe(III) in Caco-2 cells and compared this with sample solutions
      without organic acids but set to equivalent pH by HCl. The results showed that
      the mechanisms behind the enhancing effect of organic acids differed for the two
      forms of iron. For ferric iron the organic acids promoted uptake both by
      chelation and by lowering the pH, whereas for ferrous iron the promoting effect
      was caused only by the lowered pH.

PMID- 14664553
TI  - Phytochemical profiles and antioxidant activity of wheat varieties.
AB  - Whole grain consumption has been associated with reduced risk of chronic
      diseases, such as cardiovascular diseases and cancer. These beneficial effects
      have been attributed to the unique phytochemicals of grains that complement those
      found in fruits and vegetables. Wheat is one of the major grains in the human
      diet; however, little is known about the inherent varietal differences in
      phytochemical profiles, total phenolic and carotenoid contents, or total
      antioxidant activities of different wheat varieties, which ultimately influence
      the associated nutritional and health benefits of wheat and wheat products. The
      objectives of this study were to determine the phytochemical profiles and total
      antioxidant activity for 11 diverse wheat varieties and experimental lines. The
      profiles included free, soluble-conjugated, and insoluble-bound forms of total
      phenolics, flavonoids, and ferulic acids and carotenoid content including lutein,
      zeaxanthin, and beta-cryptoxanthin. The results showed that total phenolic
      content (709.8-860.0 micromol of gallic acid equiv/100 g of wheat), total
      antioxidant activity (37.6-46.4 micromol of vitamin C/g), and total flavonoid
      content (105.8-141.8 micromol of catechin equiv/100 g of wheat) did not vary
      greatly among the 11 wheat lines. However, significant differences in total
      ferulic acid content (p < 0.05) and carotenoid content (p < 0.05) among the
      varieties were observed, with carotenoid content exhibiting the greatest range of
      values. Carotenoid content among the 11 wheat varieties exhibited 5-fold, 3-fold,
      and 12-fold differences in lutein, zeaxanthin, and beta-cryptoxanthin,
      respectively. A synthetic wheat experimental line, W7985, gave the lowest
      carotenoid concentrations of any of the genotypes in this study. Such large
      genotypic differences in carotenoid content may open up new opportunities for
      breeding wheat varieties with higher nutritional value.

PMID- 14664554
TI  - Fast nitroxyl trapping by ferric porphyrins.
AB  - Iron(II) porphyrin nitrosyl complexes are obtained in high yields from the
      reaction of iron(III) porphyrins with the nitroxyl donors sodium trioxodinitrate
      and toluensulfohydroxamic acid. The reaction was found to proceed both in organic
      solvents and in aqueous media from iron(III) (meso-tetraphenyl) porphyrinate
      ([FeIII(TPP)]+) and iron(III) meso-tetrakis (4-sulfonatophenyl) porphyrinate
      ([FeIII(TPPS)]3-) or iron(III) protoporphyrin IX, respectively. The kinetic rate
      constant for the reaction of ([FeIII(TPPS)]3-) with sodium trioxodinitrate (kon)
      was estimated to be 1.00 +/- 0.04 x 107 M-1 s-1. As well as resulting in a
      versatile method for obtaining ferrous nitrosyl porphyrins, the reaction points
      at ferric porphyrins as efficient nitroxyl traps and provides a tool to model
      nitroxyl reactivity toward hemeproteins.

PMID- 14664555
TI  - Template synthesis and single-molecule magnetism properties of a complex with
      spin S = 16 and a [Mn8O8]8+ saddle-like core.
AB  - The compound [CeIVMnIII8O8(O2CMe)12(H2O)4].4H2O (1.4H2O) has been obtained from a
      template synthesis involving the reaction of the chain polymer
      {[MnIII(OH)(O2CMe)2] .(MeCO2H).(H2O)}n (3) with Ce(IV). Compound 1 contains a
      MnIII8 loop inside which is held the Ce(IV) ion by the bridging oxide ions.
      Magnetization and magnetic susceptibility studies establish that 1 has an S = 16
      spin ground state, the largest yet for a Mn cluster, and displays the slow
      magnetization relaxation and hysteresis behavior of a single-molecule magnet
      (SMM). It is thus the highest spin Mn SMM discovered to date.

PMID- 14664556
TI  - Controlling diaza-Cope rearrangement reactions with resonance-assisted hydrogen
      bonds.
AB  - NMR studies reveal that the equilibrium between 1 and 2 lies essentially toward 1
      to the left without any detectable amount of 2. DFT computation shows that the
      value of K1 is about 1.4 x 10-5, and X-ray crystal structures show that the
      resonance-assisted hydrogen bond (RAHB) in 1 (1.66 A) is shorter than the regular
      hydrogen bond in 2 (1.75 A). The enormous selectivity can be explained in terms
      of the strength of the RAHBs in 1 compared to that of the regular hydrogen bonds
      in 2.

PMID- 14664557
TI  - Micropatterning of organic semiconductor microcrystalline materials and OFET
      fabrication by "hot lift off".
AB  - Considerable progress toward the development of electronic devices that rely on
      organic semiconductors as the active material component has been made in recent
      years. The key step for realization of the advanced organic electronic, or
      optical, device is the ability to micropattern different kinds of electronic
      materials, such as organic semiconductor/conducting materials, over large areas
      with micrometer-sized resolution. Here we demonstrate a simple and direct method
      for micropatterning small-molecule microcrystalline films using an epoxy stamp.
      The "hot lift off" method is highly selective, creating patterns with high
      resolution and relies on straightforwardly tailoring the adhesive properties
      between the epoxy and the film. This process is well suited for patterning many
      types of materials.

PMID- 14664558
TI  - Potent small-molecule binding to a dynamic hot spot on IL-2.
AB  - The complexes between IL-2 and two similar small molecules, one a lead compound
      and the other a potent, affinity-optimized compound, were determined by X-ray
      crystallography. The lead compound (IC50 = 6 muM) bound to a hot spot on IL-2 in
      a groove that is not apparent in either the unliganded protein or a complex
      between IL-2 and a weakly bound drug fragment. The affinity-optimized compound
      (IC50 = 0.06 muM), which has an added aromatic acid fragment, bound in the same
      groove as the lead compound. In addition, a novel binding site was formed for the
      aromatic acid which is unseen in the complex with the lead compound. Thus, the
      hot spot on IL-2 is highly dynamic, with the protein changing form at multiple
      sites to maximize packing for each compound. Binding-site rigidity is often
      thought to play a role in high-affinity interactions. However, in this case,
      specific contacts between the small molecule and the protein are made despite the
      adaptivity of the hot spot. Given the change in morphology that was observed in
      IL-2, it is unlikely that a potent inhibitor could have been found by rational
      design. Therefore, fragment assembly methods offer the stochastic advantage of
      finding fragments in flexible protein regions where structural changes are
      unpredictable.

PMID- 14664559
TI  - Unique charge transfer properties of the four-base pi-stacks in Z-DNA.
AB  - To investigate the photoreactions of BrU in Z-DNA, the photoirradiation of 5'
      d(C1G2C3G4BrU5G6C7G8)-3'/5'-d(C9mG10C11A12C13mG14C15G16)-3'(ODN 1-2) was
      investigated. In accord with previous observations, B-form ODN 1-2 with the 5'
      GBrU sequence showed very weak photoreactivity. However, Z-form ODN 1-2 in 2 M
      NaCl underwent photoreaction to afford 5'-d(CGC)rGd(UGCG)-3' together with the
      formation of imidazolone (Iz) contained 5'-d(CIzCACmGCG)-3'. The results clearly
      indicate that structural changes caused by the B-Z transition dramatically
      increased the photoreactivity of ODN 1-2. Inspection of the molecular structure
      of Z-DNA suggests that there is unique four-base pi-stacks at the G4-BrU5-C11
      mG10 in ODN 1-2. These results suggest that the intriguing possibility that the
      mG10 in a complementary strand located at the end of the four-base pi-stacks may
      act as an electron donor. To test the hypothesis of interstrand charge transfer
      from mG10 to BrU5 within the four-base pi-stacks in Z-DNA, ODN 1-3 samples in
      which the putative donor G10 residue was replaced with 8-methoxyguanine (moG)
      were prepared, since moG is known to trap cation radicals to yield Iz moieties in
      DNA. Photoirradiation of ODN 1-3 efficiently produced 5'-d(CGC)rGd(UGCG)-3'
      together with formation of 5'-d(CIzCACmGCG)-3'. These results clearly indicate
      that the interstrand charge transfer from mG10 to BrU5 initiates the
      photoreaction. In clear contrast, other replacements of G with moG did not
      enhance the photoreactivity. The present study revealed the presence of unique
      four-base pi-stacks in Z-DNA and photoirradition of BrU in Z-DNA causes efficient
      electron transfer from G within this cluster.

PMID- 14664560
TI  - Total synthesis of (+/-)-didehydrostemofoline (asparagamine A) and (+/-)
      isodidehydrostemofoline.
AB  - The first total syntheses of (+/-)-didehydrostemofoline (1) and (+/-)
      isodidehydrostemofoline (3) are reported. The synthesis begins with the Diels
      Alder reaction of readily available pyrrole 9 and ethyl (E)-3-nitroacrylate, the
      latter serving as a regioinverted equivalent of ketene. After hydrogenation to
      prevent retro-Diels-Alder reaction, the major cycloadduct is transformed to 7
      azabicyclo[2.2.1]heptanol 14. Aza-Cope-Mannich reaction of the formaldiminium
      derivative of 14 delivers 1-azatricyclo[5.3.0.04.10]decane 15, which in 15
      additional steps is converted to 1 and 3.

PMID- 14664561
TI  - Beta-diiminate platinum complexes for alkane dehydrogenation.
AB  - New five-coordinate Pt(IV) complexes [{(o-R2-p-R'-C6H2)NC(R' ')}2CH]PtMe3 (R, R',
      R' ' = alkyl or H) are reported. The complex with R = Me, R' = tBu, R' ' = Me
      generates unsaturated Pt(II) species capable of alkane C-H bond activation and
      stoichiometric dehydrogenation.

PMID- 14664562
TI  - A paramagnetic CEST agent for imaging glucose by MRI.
AB  - The europium(III) complex of a DOTA-tetraamide ligand (DOTA = 1,4,7,10
      tetraazacyclododecane-N,N',N' ',N' ''-tetraacetic acids) containing two phenyl
      boronate pendent arms binds glucose reversibly with an association constant of
      383 M-1 at pH 7. Glucose binding results in slowing of water exchange between a
      single Eu(III)-bound water molecule and bulk water, and this can be imaged by MRI
      using chemical exchange saturation transfer (CEST) imaging sequence. This
      metabolite-responsive paramagnetic CEST agent responds to changes in glucose over
      the physiologically important range (0-20 mM), and thus it offers the possibility
      of high-sensitivity MR imaging glucose in tissues using bulk water protons as
      antenna.

PMID- 14664564
TI  - Palladium-catalyzed Stille cross-couplings of sulfonyl chlorides and
      organostannanes.
AB  - Arene and phenylmethanesulfonyl chlorides can be cross-coupled with aryl,
      heteroaryl, and alkenylstannanes with desulfitation in the presence of 10 mol %
      CuBr.Me2S, 1.5 mol % Pd2dba3, and 5 mol % tri-2-furylphosphine in tetrahydrofuran
      or toluene under reflux. This extension of the Stille cross-coupling reaction
      realizes a new and economical method for the generation of C-C bonds. The
      palladium-catalyzed carbonylative Stille cross-coupling reactions of
      arenesulfonyl chlorides and organostannanes in the presence of CO (60 bar) at 110
      degrees C in toluene generate the corresponding ketones. Arenesulfonyl chlorides
      are more reactive than aryl chlorides and aryl bromides in their Stille cross
      coupling with organostannanes but less reactive than aryl iodides. The new
      methods disclosed for the generation of C-C bonds open new possibilities for
      medicinal chemistry and material sciences.

PMID- 14664563
TI  - Oxygen is electroreduced to water on a "wired" enzyme electrode at a lesser
      overpotential than on platinum.
AB  - The first enzyme-based catalyst that is superior to platinum in the four-electron
      electroreduction of oxygen to water is reported. The smooth Pt cathode reached
      half and 90% of the mass transport-limited current density at respective
      overpotentials of -0.4 and -0.58 V in 0.5 M sulfuric acid, and only at even
      higher overpotentials in pH 7.2 phosphate buffer. In contrast, the smooth "wired"
      bilirubin oxidase cathode reached half and 90% of the mass transport-limited
      current density at respective overpotentials as low as -0.2 and -0.25 V. The mass
      transport-limited current density for the smooth "wired" enzyme cathode in PBS
      was twice that with smooth Pt in 0.5 M sulfuric acid. Under 1 atm O2 pressure, O2
      was electroreduced to water on a polished carbon cathode, coated with the "wired"
      BOD film, in pH 7.2 saline buffer (PBS) at an overpotential of -0.31 V at a
      current density of 9.5 mA cm-2. At the same overpotential, the current density of
      the polished platinum cathode in 0.5 M H2SO4 was 16-fold lower, only 0.6 mA cm-2.

PMID- 14664565
TI  - Redox state dependence of single molecule conductivity.
AB  - Spontaneous formation of stable molecular wires between a gold scanning tunneling
      microscopy (STM) tip and substrate is observed when the sample has a low coverage
      of alpha,omega-dithiol molecules and the tunneling resistance is made
      sufficiently small. Current-distance curves taken under these conditions exhibit
      characteristic current plateaux at large tip-substrate separations from which the
      conductivity of a single molecule can be obtained. The versatility of this
      technique is demonstrated using redox-active molecules under potential control,
      where substantial reversible conductivity changes from 0.5 to 2.8 nS were
      observed when the molecule was electrochemically switched from the oxidized to
      the reduced state.

PMID- 14664566
TI  - Glycosidase-substrate interactions analysis by STD-NMR spectroscopy: study of
      alpha-L-fucosidase.
AB  - Saturation transfer difference-nuclear magnetic resonance (STD-NMR) is a recently
      developed method used to study the interaction between large proteins and small
      ligands. It has been successfully employed for various interactions including
      those between oligosaccharides or glycomimetics, and binding proteins such as
      lectins and antibodies. We have demonstrated that this method can be used to
      directly study the interaction between glycosidases and their substrates. We
      chose to study alpha-l-fucosidases, which, despite their wide distribution among
      living organisms and their biological significance, have not been studied with
      regard to their reaction mechanism. We were able for the first time to show
      direct evidences for the minimum structural requirements for a compound to
      interact with these enzymes. These findings will be useful for the design of new
      inhibitors and to optimize the synthetic properties (transglycosylation) of alpha
      l-fucosidases.

PMID- 14664567
TI  - First estimation of C4-H bond dissociation energies of NADH and its radical
      cation in aqueous solution.
AB  - The heterolytic and homolytic C4-H bond dissociation energies of NADH and its
      radical cation (NADH*+) in aqueous solution were estimated according to the
      reaction of NADH with N,N,N',N'-tetramethyl-p-phenylenediamine radical cation
      perchlorate (TMPA*+) in aqueous solution. The results show that the values of the
      heterolytic and homolytic C4-H bond dissociation energies of NADH in aqueous
      solution are 53.6 and 79.3 kcal/mol, respectively; the values of the heterolytic
      and homolytic C4-H bond dissociation energies of NADH*+*+ in aqueous solution are
      5.1 and 36.3 kcal/mol, respectively, which, to our knowledge, is first reported.
      This energetic information disclosed in the present work should be believed to
      furnish hints to the understanding of the mechanisms for the redox
      interconversions of coenzyme couple NADH/NAD+ in vivo.

PMID- 14664568
TI  - Shape memory effect exhibited by smectic-C liquid crystalline elastomers.
AB  - It was long expected and recently shown that main-chain liquid crystalline
      elastomers (MC-LCEs) may serve as high performance soft actuators due to a
      coupling of their intrinsic characteristics of high, yet labile, ordering and
      network strain. Here, we present the synthesis of new siloxane-based smectic MC
      LCEs. These new materials exhibit a unique thermomechanical behavior known as the
      shape memory effect, which has never been observed before in such LCEs. To
      achieve targeted transition temperatures required for facile actuation at low
      temperatures, specifically temperatures ranging from 15 to 65 degrees C, we have
      designed and prepared such elastomers incorporating two distinct mesogenic
      groups, termed 5H and 5tB, coupled with hydride-terminated poly(dimethylsiloxane)
      spacers.

PMID- 14664569
TI  - Orthogonal control of dissociation dynamics relative to thermodynamics in a main
      chain reversible polymer.
AB  - A pair of homologous and soluble reversible polymers display nearly identical
      solution structures but dramatically different dissociation dynamics (1.0 vs ca.
      100 s-1) along their main chains. The polymers are formed by organopalladium
      pyridine coordination, and steric effects at the metal center control the
      dynamics. Importantly, the association constant is not significantly affected by
      the sterics. The resulting orthogonal control over dissociation kinetics provides
      a general tool for studying the effects of dynamics independent of thermodynamics
      in supramolecular systems, particularly main-chain reversible polymers.

PMID- 14664570
TI  - Synthesis, structure, and reaction of 1-alkynyl(aryl)-lambda3-bromanes.
AB  - Reported here for the first time are the synthesis, structure, and reaction of
      hypervalent 1-alkynyl(aryl)-lambda3-bromanes. BF3-catalyzed ligand exchange on
      bromine(III) of p-trifluoromethylphenyl(difluoro)-lambda3-bromane with 1
      alkynyl(trimethyl)stannanes in dichloromethane at -78 degrees C afforded 1
      alkynyl(aryl)-lambda3-bromanes in good yields.
      Trimethyl(trimethylsilylethynyl)stannane gave silylethynyl-lambda3-bromane
      selectively. 13C NMR chemical shifts of acetylenic carbon atoms of
      alkynylbromanes are compared with those of alkynyl-lambda3-iodanes and explained
      in terms of the spin-orbit-induced heavy atom effects. The structure of tert
      butylethynylbromane was established by a single-crystal X-ray analysis of its
      crown ether complex. The 1-alkynyl(aryl)-lambda3-bromanes serve as highly
      electron-deficient Michael acceptors and undergo tandem Michael-carbene
      rearrangements by the reaction with sulfonate anions, yielding 1-alkynyl
      sulfonates.

PMID- 14664571
TI  - Switching by pulse electric field of the elevated enzymatic reaction in the core
      of polyion complex micelles.
AB  - Polyion complex micelles entrapping enzyme molecules in the core provide a unique
      reaction field inducing a remarkable elevation of enzymatic reactivity through a
      drastic change in the binding specificity between the enzyme and substrate. On
      off switching of this enhanced effect was achieved through the destabilization of
      the core domain by applying a pulse electric field.

PMID- 14664572
TI  - The surprising nitrogen-analogue chemistry of the methyltrioxorhenium-catalyzed
      olefin epoxidation.
AB  - Density functional theory calculations at the B3LYP level have been carried out
      to investigate the mechanism of the reaction of ethylene with [Re(O)2(O-NH)Me], a
      formal hydroxylamine derivative of the industrial epoxidation catalyst
      methyltrioxorhenium(VII) (MTO). A variety of reaction pathways has been
      considered, including the concerted heteroatom-transfer mechanism postulated by
      Sharpless and the stepwise mechanism via a five-membered "organometallacycle"
      postulated by Mimoun. Ethylene has been found not to coordinate directly at the
      metal. The calculations reveal similar activation free enthalpies for the
      concerted nitrene-transfer event (aziridination) and for the formation of an
      organometallic rhena-2,3-oxazolidine via [2+2] addition of ethylene across the Re
      N bond of the metallaoxaziridine moiety. The fragmentation of the
      organometallacycle is faster than its formation and gives ethylideneazane rather
      than aziridine. An additional pathway has a lower activation free enthalpy and
      leads to a rhena-3,2-oxazolidine. The formation of this organometallacycle
      proceeds via an intermediate ring-opening product, [Re(O)2(eta1-O-NH)Me], which
      undergoes [3+2] cycloaddition across the C=C bond of ethylene. Analysis of its
      electronic structure reveals that the eta1 species should be considered a metalla
      analogue nitrosonium ylide rather than a metalla-analogue imine oxide.
      Fragmentation of the rhena-3,2-oxazolidine liberates acetaldehyde. The discovery
      of favorable pathways leading to organometallacycles upon reaction of C=C bonds
      with [Re(O)2(O-NH)Me] stands in sharp contrast to the strong preference of the
      concerted mechanism in the olefin epoxidation with rhenium peroxo complexes. The
      calculations show the multiple mechanisms to be distinguishable by four different
      products, calling for further experimental studies. The successful search for the
      five-membered organometallacycles parallels the computational prediction of four
      membered organometallacycles derived from d0 metal oxo complexes (Deubel, D. V.;
      Frenking, G. Acc. Chem. Res. 2003, 36, 645) and the indirect observation of
      metalla-2-oxetanes in recent gas-phase experiments (Chen, X.; Zhang, X.; Chen, P.
      Angew. Chem., Int. Ed. 2003, 42, 3798).

PMID- 14664573
TI  - Characterization of the triplet state of tris(8-hydroxyquinoline)aluminium(III)
      in benzene solution.
AB  - The lowest triplet state of tris(8-hydroxyquinoline)aluminium(III) (Alq3) has
      been prepared by pulse radiolysis/energy transfer from appropriate donors in
      benzene solutions and has an absorption maximum around 510 nm with a lifetime of
      about 50 mus. It is quenched by molecular oxygen, leading to singlet oxygen
      formation. From flash photolysis and singlet oxygen formation measurements, a
      quantum yield of triplet formation of 0.24 was determined for direct photolysis
      of the complex. A value of 2.10 +/- 0.10 eV was determined for the energy of the
      lowest triplet state by energy transfer studies and was confirmed by
      phosphorescence measurements on Alq3, either in the heavy atom solvent ethyl
      iodide or photosensitized by benzophenone in benzene. Dexter (exchange) energy
      transfer was observed from triplet Alq3 to platinum(II) octaethylporphyrin.

PMID- 14664574
TI  - Aerobic ruthenium-catalyzed oxidative cyanation of tertiary amines with sodium
      cyanide.
AB  - RuCl3-catalyzed oxidative cyanation of tertiary amines with sodium cyanide under
      molecular oxygen (1 atm) at 60 degrees C gives the corresponding alpha
      aminonitriles, which are versatile synthetic intermediates of various compounds
      such as amino acids and unsymmetrical 1,2-diamines, in excellent yields. This
      reaction is clean and should be an environmentally benign and useful process.

PMID- 14664575
TI  - Conformational studies of a bombolitin III-derived peptide mimicking the four
      helix bundle structural motif of proteins.
AB  - Bombolitins are five structurally related heptadecapeptides originally isolated
      from the venom of a bumblebee. In aqueous solution, bombolitins at sufficiently
      high concentration form oligomeric aggregates with consequent conformational
      transition from a random coil to the alpha-helical structure. Previous studies
      suggested that oligomeric aggregates could mimic the four-helix bundle structural
      motif of proteins. In the present work, we synthesized the following peptide
      sequence formed by two bombolitin III sequences linked head-to-tail by the
      tetrapeptide bridge -Gly-Pro-Val-Asp-: I(1)-K(2)-I(3)-M(4)-D(5)-I(6)-L(7)-A(8)
      K(9)-L(10)-G(11)-K(12)-V(13)-L(14)-A(15)-H(16)-V(17)-G(18)-P(19)-V(20)-D(21)
      I(22)-K(23)-I(24)-M(25)-D(26)-I(27)-L(28)-A(29)-K(30)-L(31)-G(32)-K(33)-V(3)(4)
      L(35)-A(36)-H(37)-V(38)-NH(2). The tetrapeptide GPVD connecting the two helical
      peptide sequences was chosen to facilitate the formation of the helix-loop-helix
      structural motif. The conformational properties of the peptide were studied by
      CD, NMR, and molecular dynamics calculations. The results indicate the presence
      of a helix-loop-helix conformation at 10(-)(5) M concentration. At higher
      concentrations, NOESY connectivities were detected which are compatible with the
      presence of dimers or higher aggregates of peptide molecules in the helix-loop
      helix structure packed in an antiparallel fashion. Molecular dynamics simulation
      were run either with NOE distance restraints or without restraints in explicit
      solvent for extended time. The results of these simulations support the
      dimerization of the molecules in the helix-loop-helix structure with formation of
      the four-helix bundle motif.

PMID- 14664576
TI  - Ureases: quantum chemical calculations on cluster models.
AB  - Herein, we present results from a computational study of dinickel complexes that
      are relevant to the catalytic hydrolysis of urea exerted by the urease enzymes.
      The B3LYP density functional is used to characterize the equilibrium geometry,
      electronic and magnetic properties, and energies for a series of realistic
      complexes modeling the active site of ureases. The analysis of the theoretical
      results gives new insight into the structure, substrate binding, and catalytic
      mechanism. The water bridge between the two Ni(II) ions observed in the
      crystallographic structures of the ureases was assigned to a hydroxide bridge in
      agreement with the observed small antiferromagnetic coupling. Both monodentate
      and bidentate urea-bound complexes, in which urea had favorable orientations for
      catalysis, were characterized. Finally, two reaction mechanisms were investigated
      starting from the monodentate and bidentate urea-bound complexes, respectively.
      Both a Ni1...Ni2 bridging hydroxide and a Ni2-bound water molecule play crucial
      roles in the two mechanisms.

PMID- 14664577
TI  - Propagation of melting cooperativity along the phosphodiester backbone of DNA.
AB  - The role of the DNA phosphodiester backbone in the transfer of melting
      cooperativity between two helical domains was experimentally addressed with a
      helix-bulge-helix DNA model, in which the bulge consisted of a varying number of
      either conformationally flexible propanediol or conformationally constrained
      bicyclic anucleosidic phosphodiester backbone units. We found that structural
      communication between two double helical domains is transferred along the DNA
      backbone over the equivalent of ca. 12-20 backbone units, depending on whether
      there is a symmetric or asymmetric distribution of the anucleosidic units on both
      strands. We observed that extension of anucleosidic units on one strand only
      suffices to disrupt cooperativity transfer in a similar way as if extension
      occurs on both strands, indicating that the length of the longest anucleosidic
      inset determines cooperativity transfer. Furthermore, conformational rigidity of
      the sugar unit increases the distance of coopertivity transfer along the
      phosphodiester backbone. This is especially the case when the units are
      asymmetrically distributed in both strands.

PMID- 14664578
TI  - The A-cluster in subunit beta of the acetyl-CoA decarbonylase/synthase complex
      from Methanosarcina thermophila: Ni and Fe K-edge XANES and EXAFS analyses.
AB  - The acetyl-CoA decarbonylase/synthase (ACDS) complex catalyzes the cleavage of
      acetyl-CoA in methanogens that metabolize acetate to CO(2) and CH(4), and also
      carries out acetyl-CoA synthesis during growth on one-carbon substrates. The ACDS
      complex contains five subunits, among which beta possesses an Ni-Fe-S active-site
      metal cluster, the A-cluster, at which reaction with acetyl-CoA takes place,
      generating an acetyl-enzyme species poised for C-C bond cleavage. We have used Ni
      and Fe K fluorescence XANES and EXAFS analyses to characterize these metals in
      the ACDS beta subunit, expressed as a C-terminally shortened form. Fe XANES and
      EXAFS confirmed the presence of an [Fe(4)S(4)] cluster, with typical Fe-S and Fe
      Fe distances of 2.3 and 2.7 A respectively. An Fe:Ni ratio of approximately 2:1
      was found by Kalphabeta fluorescence analysis, indicating 2 Ni per [Fe(4)S(4)].
      Ni XANES simulations were consistent with two distinct Ni sites in cluster A, and
      the observed spectrum could be modeled as the sum of separate square planar and
      tetrahedral Ni sites. Treatment of the beta subunit with Ti(3+) citrate resulted
      in shifts to lower energy, implying significant reduction of the [Fe(4)S(4)]
      center, along with conversion of a smaller fraction of Ni(II) to Ni(I). Reaction
      with CO in the presence of Ti(3+) citrate generated a unique Ni XANES spectrum,
      while effects on the Fe-edge were not very different from the reaction with
      Ti(3+) alone. Ni EXAFS revealed an average Ni coordination of 2.5 S at 2.19 A and
      1.5 N/O at 1.89 A. A distinct feature at approximately 2.95 A most likely results
      from Ni-Ni interaction. The methanogen beta subunit A-cluster is proposed to
      consist of an [Fe(4)S(4)] cluster bridged to an Ni-Ni center with one Ni in
      square planar geometry coordinated by 2 S + 2 N and the other approximately
      tetrahedral with 3 S + 1 N/O ligands. The electronic consequences of two distinct
      Ni geometries are discussed.

PMID- 14664579
TI  - Protein film voltammetry of Rhodobacter capsulatus xanthine dehydrogenase.
AB  - Xanthine dehydrogenase (XDH) from the bacterium Rhodobacter capsulatus catalyzes
      the hydroxylation of xanthine to uric acid with NAD(+) as the electron acceptor.
      R. capsulatus XDH forms an (alphabeta)(2) heterotetramer and is highly homologous
      to homodimeric eukaryotic XDHs. The crystal structures of bovine XDH and R.
      capsulatus XDH showed that the two proteins have highly similar folds; however,
      R.capsulatus XDH is at least 5 times more active than bovine XDH and, unlike
      mammalian XDH, does not undergo the conversion to the oxidase form. Here we
      demonstrate electrocatalytic activity of the recombinant enzyme, expressed in
      Escherichia coli, while immobilized on an edge plane pyrolytic graphite working
      electrode. Furthermore, we have determined all redox potentials of the four
      cofactors (Mo(VI/V), Mo(V/IV), FAD/FADH, FADH/FADH(2) and two distinct [2Fe
      2S](2+/+) clusters) using a combination of potentiometric and voltammetric
      methods. A novel feature identified in catalytic voltammetry of XDH concerns the
      potential for the onset of catalysis (ca. 400 mV), which is at least 600 mV more
      positive than that of the highest potential cofactor. This unusual observation is
      explained on the basis of a pterin-associated oxidative switch during voltammetry
      that precedes catalysis.

PMID- 14664580
TI  - A molecular switch in amyloid assembly: Met35 and amyloid beta-protein
      oligomerization.
AB  - Aberrant protein oligomerization is an important pathogenetic process in vivo. In
      Alzheimer's disease (AD), the amyloid beta-protein (Abeta) forms neurotoxic
      oligomers. The predominant in vivo Abeta alloforms, Abeta40 and Abeta42, have
      distinct oligomerization pathways. Abeta42 monomers oligomerize into
      pentamer/hexamer units (paranuclei) which self-associate to form larger
      oligomers. Abeta40 does not form these paranuclei, a fact which may explain the
      particularly strong linkage of Abeta42 with AD. Here, we sought to determine the
      structural elements controlling paranucleus formation as a first step toward the
      development of strategies for treating AD. Because oxidation of Met(35) is
      associated with altered Abeta assembly, we examined the role of Met(35) in
      controlling Abeta oligomerization. Oxidation of Met(35) in Abeta42 blocked
      paranucleus formation and produced oligomers indistinguishable in size and
      morphology from those produced by Abeta40. Systematic structural alterations of
      the C(gamma)(35)-substituent group revealed that its electronic nature, rather
      than its size (van der Waals volume), was the factor controlling oligomerization
      pathway choice. Preventing assembly of toxic Abeta42 paranuclei through selective
      oxidation of Met(35) thus represents a potential therapeutic approach for AD.

PMID- 14664581
TI  - Direct evaluation of a mechanism for activation of the RecA nucleoprotein
      filament.
AB  - The RecA protein of Escherichia coli controls the SOS response for DNA damage
      tolerance and plays a crucial role in recombinational DNA repair. The formation
      of a RecA.ATP.ssDNA complex initiates all RecA activities, and yet this process
      is not understood at the molecular level. An analysis of RecA.DNA interactions
      was performed using both a mutant RecA protein containing a tryptophan (Trp)
      reporter and oligodeoxyribonucleotides (ODNs) containing a fluorescent guanine
      analogue, 6-methylisoxanthopterin (6MI). Experiments using fluorescent ODNs
      allowed structurally distinct nucleoprotein filaments, formed in the absence and
      presence of ATPgammaS (a slowly hydrolyzed analogue of ATP), to be differentiated
      directly. Stopped-flow spectrofluorometry, combined with presteady-state kinetic
      analyses, revealed unexpected differences in the rates of RecA.ODN and
      RecA.ATPgammaS.ODN complex assembly. This is the first demonstration that such
      intrinsically fluorescent synthetic DNAs can be used to characterize definitively
      the real-time assembly and activation of RecA.ssDNA complexes. Surprisingly, the
      ssDNA binding event is almost 50-fold slower in the presence of the activating
      ATPgammaS cofactor. Furthermore, a combination of time-dependent emission changes
      from 6MI and Trp allowed the first direct chemical test of whether an inactive
      filament can isomerize to the active state. The results revealed that, unlike the
      hexameric motor proteins, the inactive RecA filament cannot directly convert to
      the active state upon ATPgammaS binding. These results have implications for
      understanding how a coincidence of functions--an ATP-communicated signal-like
      activity and an ATP-driven motorlike activity--are resolved within a single
      protein molecule.

PMID- 14664582
TI  - Hemilabile ligands in organolithium chemistry: substituent effects on lithium ion
      chelation.
AB  - The lithium diisopropylamide-mediated 1,2-elimination of 1-bromocyclooctene to
      provide cyclooctyne is investigated using approximately 50 potentially hemilabile
      polyethers and amino ethers. Rate laws for selected ligands reveal chelated
      monomer-based pathways. The dependence of the rates on ligand structure shows
      that anticipated rate accelerations based on the gem-dimethyl effect are
      nonexistent and that substituents generally retard the reaction. With the aid of
      semiempirical and DFT computational studies, the factors influencing chelation
      are discussed. It seems that severe buttressing within chelates of the
      substitutionally rich ligands precludes a net stabilization of the chelates
      relative to nonchelated (eta(1)-solvated) forms. One ligand-MeOCH(2)CH(2)NMe(2)
      appears to promote elimination uniquely by a higher-coordinate monomer-based
      pathway.

PMID- 14664583
TI  - Infrared study of the stability and folding kinetics of a 15-residue beta
      hairpin.
AB  - The thermal stability and folding kinetics of a 15-residue beta-hairpin
      (SESYINPDGTWTVTE) have been studied by using infrared (IR) spectroscopy coupled
      with laser-induced temperature-jump (T-jump) technique for rapid folding
      unfolding initiation. An alternative method based on analyzing IR difference
      spectra was also introduced to obtain thermodynamic properties of beta-sheets,
      which complements the commonly used circular dichroism (CD) and fluorescence
      techniques. Equilibrium IR measurements indicate that the thermal unfolding of
      this beta-hairpin is fairly broad. However, it can be described by a two-state
      transition with a thermal melting temperature of approximately 29 degrees C. Time
      resolved IR measurements following a T-jump, probed at 1634 cm(-1), indicate that
      the folding of this beta-hairpin follows first-order kinetics and is amazingly
      fast. At 300 K, the folding time is approximately 0.8 micros, which is only 2-3
      times slower than that of alpha-helix formation. Additionally, the energetic
      barrier for folding is small (approximately 2 kcal mol(-1)). These results, in
      conjunction with results from other studies, support a view that the details of
      native contacts play a dominant role in the kinetics of beta-hairpin folding.

PMID- 14664584
TI  - Catalysis of the photo-Fries reaction: antibody-mediated stabilization of high
      energy states.
AB  - A conformationally constrained hapten is presented that is capable of catalyzing
      the first antibody-mediated photo-Fries rearrangement. In this reaction,
      absorption of light energy by a diphenyl ether substrate results in homolytic C-O
      bond cleavage followed by recombination to yield biphenyl-derived products. The
      most proficient antibody studied converts 4-phenoxyaniline 15 into 2-hydroxy-5
      aminobiphenyl 16 under high-intensity irradiation at a rate of 8.6 microM/min.
      These results support a recent hypothesis stating that immunization with
      conformationally constrained haptens provides higher titers for the acquisition
      of simple binding antibodies; however, in this case, conformational constraint
      does not ensure the development of more efficient catalysts. Using the obtained
      antibodies, the presence of products resulting from escape of free radicals from
      the solvent cage can be suppressed, altering the excited state energy surface
      such that free radicals are funneled into the formation of the desired biphenyl
      product. However, studies also show the inactivation of the antibodies as a
      result of photodecay of the biphenyl product. Using an isocyanate scavenging
      resin, the photodecay product could be removed and the inactivation of the
      antibody drastically reduced. Furthermore, despite the observed photodecay,
      turnover of the antibody was present; this represents the first case in which
      true turnover of a photochemical reaction using a catalytic antibody could be
      observed.

PMID- 14664585
TI  - Axial chirality in 1,4-disubstituted (ZZ)-1,3-dienes. Surprisingly low energies
      of activation for the enantiomerization in synthetically useful fluxional
      molecules.
AB  - Trialkylsilyltrialkylstannes (R(3)Si-SnR'(3)) add to 1,6-diynes in the presence
      of Pd(0) and tris-pentaflurophenylphosphine to give 1,2-dialkylidenecyclopentanes
      with terminal silicon and tin substituents. The (ZZ)-geometry of these s-cis-1,3
      dienes, resulting from the organometallic reaction mechanisms involved, forces
      the silicon and tin groups to be nonplanar, thus making the molecules axially
      chiral. There is rapid equilibration between the two helical forms at room
      temperature irrespective of the size of the Si and Sn substituents. However, the
      two forms can be observed by 1H, 13C, and 119Sn NMR spectroscopy at low
      temperature. The rates of enantiomerization, which depend on the Si and Sn
      substituents, and the substitution pattern of the cylopentane ring can be studied
      by dynamic NMR spectroscopy using line shape analysis. The surprisingly low
      energies of activation (DeltaG++ = 52-57 kJ mol(-1)) for even the bulky Si and Sn
      derivatives may be attributed to a widening of the exo-cyclic bond-angles of the
      diene carbons.

PMID- 14664586
TI  - Ionic liquids by proton transfer: vapor pressure, conductivity, and the relevance
      of DeltapKa from aqueous solutions.
AB  - We describe the behavior of the conductivity, viscosity, and vapor pressure of
      various binary liquid systems in which proton transfer occurs between neat
      Bronsted acids and bases to form salts with melting points below ambient. Such
      liquids form an important subgroup of the ionic liquid (IL) class of reaction
      media and electrolytes on which so much attention is currently being focused.
      Such "protic ionic liquids" exhibit a wide range of thermal stabilities. We find
      a simple relation between the limit set by boiling, when the total vapor pressure
      reaches one atm, and the difference in pK(a) value for the acid and base
      determined in dilute aqueous solutions. For DeltapK(a) values above 10, the
      boiling point elevation becomes so high (>300 degrees C) that preemptive
      decomposition prevents its measurement. The completeness of proton transfer in
      such cases is suggested by the molten salt-like values of the Walden product,
      which is used to distinguish good from poor ionic liquids. For the good ionic
      liquids, the hydrogen bonding of acid molecules to the proton-transfer anion is
      strong enough that boiling points, but not melting points, may maximize at the
      hydrogen-bonded dianion composition. High boiling liquids of this type constitute
      an interesting class of high-temperature protonic acid that may have high
      temperature fuel cell applications.

PMID- 14664587
TI  - Dimerizations of nitrile oxides to furoxans are stepwise via dinitrosoalkene
      diradicals: a density functional theory study.
AB  - Density functional theory calculations at the B3LYP/6-31G* level on the
      dimerization reactions of acetonitrile oxide and para-chlorobenzonitrile oxide to
      form furoxans indicate that these processes are stepwise involving
      dinitrosoalkene intermediates that have considerable diradical character. The
      rate-determining steps for these two reactions correspond to C-C bond formation.
      The retardation of dimerization in aromatic nitrile oxides arises from the
      interruption of conjugation between the nitrile oxide and aryl groups in the C-C
      bond formation step. The present study also suggests that the isomerization of
      single-ring furoxans occurs via a diradical intermediate mechanism.

PMID- 14664588
TI  - Mechanisms of exchange modulation in trimethylenemethane-type biradicals: the
      roles of conformation and spin density.
AB  - The molecular structures and magnetic properties of six dinitroxide biradicals
      are described. Five of the dinitroxides are trimethylenemethane-type (TMM-type)
      biradicals; that is, the intramolecular exchange parameter, J, is modulated by a
      carbon-carbon double bond. However, the efficacy of the carbon-carbon double bond
      as an exchange coupler is determined by the molecular conformation. Our results
      show that the exchange parameters correlate with phenyl-ring torsion angles (phi)
      via a simple Karplus-Conroy-type relation: J = 44 cos(2) phi - 17. Comparison of
      these results to those obtained for our isostructural series of bis(semiquinone)
      biradicals shows that both the magnitude of J and the resistance of ferromagnetic
      J to bond torsions is proportional to the spin density adjacent to the exchange
      coupler.

PMID- 14664589
TI  - Total synthesis of apoptolidin: construction of enantiomerically pure fragments.
AB  - A general strategy for the total synthesis of the antitumor agent apoptolidin (1)
      is proposed, and the chemical synthesis of the defined key building blocks (4, 5,
      6, 8, and 9) in their enantiomerically pure forms is described. The projected
      total synthesis calls for a dithiane coupling reaction to construct the C(20)
      C(21) bond, a Stille coupling reaction to form the C(11)-C(12) bond, and a
      Yamaguchi macrolactonization to assemble the macrolide ring, as well as two
      glycosidation reactions to fuse the carbohydrate units onto the molecule. First
      and second generation syntheses to the required fragments for apoptolidin (1) are
      described.

PMID- 14664590
TI  - Total synthesis of apoptolidin: completion of the synthesis and analogue
      synthesis and evaluation.
AB  - The total synthesis of apoptolidin (1) is reported together with the design,
      synthesis, and biological evaluation of a number of analogues. The assembly of
      key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was
      supplemented by a second generation route to this advanced intermediate involving
      a Horner-Wadsworth-Emmons coupling of fragments 22 and 25. The final stages of
      the synthesis featured a Stille coupling between vinyl iodide 3 and vinylstannane
      2, a Yamaguchi lactonization, a number of glycosidations, and final deprotection.
      The developed synthetic technology was applied to the construction of several
      analogues including 74, 75, and 77 which exhibit significant bioactivity against
      tumor cells.

PMID- 14664592
TI  - Mechanisms of metal ion transfer into room-temperature ionic liquids: the role of
      anion exchange.
AB  - The structure and stoichiometry of the lanthanide(III) (Ln) complexes with the
      ligand 2-thenoyltrifluoroacetone (Htta) formed in a biphasic aqueous room
      temperature ionic liquid system have been studied by complementary
      physicochemical methods. Equilibrium thermodynamics, optical absorption and
      luminescence spectroscopies, high-energy X-ray scattering, EXAFS, and molecular
      dynamics simulations all support the formation of anionic Nd(tta)4(-) or
      Eu(tta)4(-) complexes with no water coordinated to the metal center in 1-butyl-3
      methylimidazolium bis[(trifluoromethyl)sulfonyl]imide (C4mim+Tf2N(-)), rather
      than the hydrated, neutral complexes, M(tta)(3)(H2O)n)(n = 2 or 3), that form in
      nonpolar molecular solvents, such as xylene or chloroform. The presence of
      anionic lanthanide complexes in C4mim+Tf2N(-) is made possible by the exchange of
      the ionic liquid anions into the aqueous phase for the lanthanide complex. The
      resulting complexes in the ionic liquid phase should be thought of as weak
      C4mim+Ln(tta)4(-) ion pairs which exert little influence on the structure of the
      ionic liquid phase.

PMID- 14664591
TI  - Kinetic and thermodynamic barriers to carbon and oxygen alkylation of phenol and
      phenoxide ion by the 1-(4-methoxyphenyl)ethyl carbocation.
AB  - Rate constant ratios for addition of the three nucleophilic sites of phenol to
      the 1-(4-methoxyphenyl)ethyl carbocation (1+) in 50/50 (v/v)
      trifluoroethanol/water were determined from the relative yields of the three
      phenol adducts, and absolute rate constants were determined from product rate
      constant ratios for addition of phenol and azide ion to 1+ using k(az) = 5 x
      10(9) M(-1) s(-1) for the diffusion-limited reaction of azide ion. A selectivity
      of 230:20:1 was determined for alkylation of phenol at oxygen, C-4 and C-2 to
      form 1-OPh and biphenyls 1-(4-C6H4OH) and 1-(2-C6H4OH), respectively, and of
      2:2:1 for alkylation of the corresponding nucleophilic sites of phenoxide ion in
      diffusion-limited reactions. The Mayr nucleophilicity parameter for C-4 of phenol
      is N = 2.0. Encounter-limited addition of phenoxide ion to 1+ to form 1-OPh is
      faster than encounter-limited addition of oxygen anions that are either more or
      less basic than phenoxide ion. Only the products of solvolysis are observed from
      acid-catalyzed cleavage of 1-OPh in 50/50 (v/v) trifluoroethanol/water, but a 50%
      yield of biphenyls 1-(4-C6H4OH) and 1-(2-C6H4OH) are observed from spontaneous
      cleavage of 1-OPh, where the leaving group is phenoxide ion, because of the very
      low kinetic barriers to collapse of the ion pair intermediate 1+.PhO-. The 230
      fold larger rate constant for O-compared to C-2-alkylation of phenol is due
      primarily to the larger thermodynamic driving force for oxygen addition. There
      are similar Marcus intrinsic barriers for these two reactions.

PMID- 14664593
TI  - Synthesis, structure, and photophysical and electrochemical properties of a pi
      stacked polymer.
AB  - Dibenzofulvene (DBF) was polymerized using anionic initiators to afford a vinyl
      polymer. Oligo(DBF)s having from two to eight side-chain fluorene moieties
      bearing different chain-terminal groups were isolated by preparative size
      exclusion chromatography. The structures of the isolated oligomers were revealed
      by single-crystal X-ray and (1)H NMR analyses. Both in solution and in crystal,
      the in-chain fluorene moieties stacked on top of each other, while the terminal
      conformation varied depending on the terminal group. These conformational
      characteristics were supported by molecular mechanics and dynamics calculations.
      The oligomers and polymers indicated hypochromism and red shift in UV absorption
      spectra and exclusive excimer emission in fluorescence spectra. In addition,
      reduced oxidation potentials were observed for the oligomers in electrochemical
      analyses, which suggests charge delocalization over the pi-stacked electron
      systems. The photophysical and electrochemical effects increased with the chain
      length of the oligomers and leveled off around the chain length of an oligomer
      consisting of five fluorene units.

PMID- 14664594
TI  - Dendritic molecular capsules for hydrophobic compounds.
AB  - Reichardt's dye, a highly solvatochromic dye, was encapsulated within poly
      (glycerol succinic acid) ([Gn]-PGLSA-OH) dendrimers to investigate the interior
      environment of these dendritic macromolecules. The absorption maximum for the
      encapsulated Reichardt's dye in water was indicative of a relatively high
      dielectric constant present within the dye/dendrimer complex. (1)H NMR of the
      encapsulated complex showed the presence of aromatic protons from Reichardt's dye
      along with the aliphatic protons of the dendrimer. Additionally, there were
      substantial changes in T(1) and T(2) times of the encapsulated dye when compared
      with the free dye, and (1)H NOESY spectra for the complex showed a significant
      number of intermolecular NOE cross-peaks. These data reveal the close through
      space proximity of the dye to the dendrimer and the restricted motion of the
      encapsulated dye. To demonstrate the potential use of these macromolecules as
      drug delivery vehicles, the poorly water-soluble anticancer drug 10
      hydroxycamptothecin (10HCPT) was encapsulated within a carboxylated PGLSA
      dendrimer ([G4]-PGLSA-COONa). Cytotoxicity assays with human breast cancer cells
      showed a significant reduction of cell viability, demonstrating that 10HCPT
      retains activity upon encapsulation.

PMID- 14664595
TI  - Assembly of an electronically switchable rotaxane on the surface of a titanium
      dioxide nanoparticle.
AB  - This paper describes the self-assembly of a heterosupramolecular system
      consisting of a tripodal [2]rotaxane adsorbed at the surface of a titanium
      dioxide nanoparticle. The tripodal [2]rotaxane consists of a dumbbell-shaped
      molecule, incorporating two electron-poor viologens, threading an electron-rich
      crown ether. The [2]rotaxane also incorporates a bulky tripodal linker group at
      one end and a bulky stopper group at the other end. The [2]rotaxane is adsorbed,
      via the tripodal linker group, at the surface of a titanium dioxide nanoparticle.
      The structure and function of the resulting hetero[2]rotaxane have been studied
      in detail by (1)H NMR spectroscopy and cyclic voltammetry. A key finding is that
      it is possible to electronically address and switch the above hetero[2]rotaxane.

PMID- 14664596
TI  - Synthesis of amphiphilic phenylazophenyl glycosides and a study of their liquid
      crystal properties.
AB  - Several 4-(4'-N,N-didodecylaminophenylazo)phenyl 1,2-trans glycosides 5a-e with
      various carbohydrate heads (beta-D-gluco, beta-D-galacto, beta-lacto, beta-D
      xylo, and alpha-D-manno) have been synthesized. The key step was the formation of
      phenyldiazonium tetrafluoroborates 2a-e from the per-O-acetylated 4-aminophenyl
      glycosides 1a-e. These salts were condensed with N,N-didodecylaniline under phase
      transfer conditions and the per-O-acetylated 4-(4'-N,N
      didodecylaminophenylazo)phenyl 1,2-trans glycosides 4a-e were fully de-O
      acetylated by the Zemplen method. The self-organizing liquid crystal properties
      of the compounds were investigated by a variety of techniques, including
      polarized light microscopy, differential scanning calorimetry, and X-ray
      diffraction. All but one of the materials exhibited smectic A, lamellar phases.
      Remarkably, the glucose derivative exhibited a rectangular disordered columnar
      phase. This result has implications with respect to the induced curvature created
      by the recognition processes of the glucose headgroup relative to the other sugar
      moieties and to the prevalence of various glycolipids in cell membranes

PMID- 14664597
TI  - Spherical sila- and germa-homoaromaticity.
AB  - Guided by the 2(N + 1)2 electron-counting rule for spherical aromatic molecules,
      we have designed various spherical sila- and germa-homoaromatic systems rich in
      group 14 elements. Their aromaticity is revealed by density-functional
      computations of their structures and the nucleus-independent chemical shifts
      (NICS). Besides the formerly used endohedral inclusion strategy, spherical
      homoaromaticity is another way to stabilize silicon and germanium clusters.

PMID- 14664598
TI  - Total syntheses of amphidinolide T1, T3, T4, and T5.
AB  - A concise, flexible, and high yielding entry into the family of amphidinolide T
      macrolides, a series of cytotoxic natural products of marine origin, has been
      developed. All individual members, except amphidinolide T3 (3), derive from
      compound 39 as a common synthetic intermediate which is formed from three
      building blocks of similar size and complexity. The fragment coupling steps
      involve a highly diastereoselective SnCl(4) mediated reaction of the furanosyl
      sulfone derivative 11 with the silyl enol ether 18 and a palladium-catalyzed
      Negishi type coupling reaction between the polyfunctional organozinc reagent
      derived from iodide 32a and the enantiopure acid chloride 24b. The 19-membered
      macrocyclic ring is then formed by a high yielding ring closing metathesis (RCM)
      reaction of diene 33 catalyzed by the "second generation" ruthenium carbene
      complex 34. The efficiency of the RCM transformation stems, to a large extent,
      from the conformational bias introduced by the syn-syn-configured stereotriad at
      C12-C14 of the substrate which constitutes a key design element of the synthesis
      plan. The use of Nysted's reagent 38 in combination with TiCl(4) was required for
      the olefination of the sterically hindered ketone group in 36, whereas more
      conventional alkene formations were unsuccessful for this elaboration. Finally,
      it is shown that the inversion of a single and seemingly remote stereocenter
      (C12) in one of the building blocks not only affects the efficiency and
      stereochemical outcome of the RCM step but also exerts a significant influence on
      the course of the acyl-Negishi reaction, allowing a radical manifold to compete
      with productive cross coupling.

PMID- 14664599
TI  - Stereochemistry of nucleophilic substitution reactions depending upon
      substituent: evidence for electrostatic stabilization of pseudoaxial conformers
      of oxocarbenium ions by heteroatom substituents.
AB  - Lewis acid-mediated nucleophilic substitution reactions of substituted
      tetrahydropyran acetates reveal that the conformational preferences of six
      membered-ring cations depend significantly upon the electronic nature of the
      substituent. Nucleophilic substitutions of C-3 and C-4 alkyl-substituted
      tetrahydropyran acetates proceeded via pseudoequatorially substituted
      oxocarbenium ions, as would be expected by consideration of steric effects.
      Substitutions of C-3 and C-4 alkoxy-substituted tetrahydropyran acetates,
      however, proceeded via pseudoaxially oriented oxocarbenium ions. The unusual
      selectivities controlled by the alkoxy groups were demonstrated for a range of
      other heteroatom substituents, including nitrogen, fluorine, chlorine, and
      bromine. It is believed that the pseudoaxial conformation is preferred in the
      ground state of the cation because of an electrostatic attraction between the
      cationic carbon center of the oxocarbenium ion and the heteroatom substituent.
      This analysis is supported by the observation that selectivity diminishes down
      the halogen series, which is inconsistent with electron donation as might be
      expected during anchimeric assistance. The C-2 heteroatom-substituted systems
      gave moderately high 1,2-cis selectivity, while small alkyl substituents showed
      no selectivity. Only in the case of the tert-butyl group at C-2 was high 1,2
      trans selectivity observed. These studies reinforce the idea that ground-state
      conformational effects need to be considered along with steric approach
      considerations.

PMID- 14664600
TI  - Preparation of thin silica films with controlled thickness and tunable refractive
      index.
AB  - Silica films with controlled thickness and refractive index have been formed by
      the sequential adsorption of a cationic polyelectrolyte and silica sols. The
      conditions used to prepare the sol were varied, and allowed films with refractive
      indices as low as 1.16 to be obtained. The sequential adsorption technique allows
      the thickness of these films to be controlled in increments of 5-10 nm, depending
      on the desired refractive index. Scanning electron microscopy revealed that a low
      packing density of constituent silica particles was responsible for the low
      indices of these films. The as-adsorbed films are thermally robust; calcination
      at 500 degrees C resulted in only very small decreases in film thickness (by < or
      =1.8%) and refractive index (to as low as 1.14). After calcination, the silica
      films remained hydrophilic and sorbed water vapor from the atmosphere. As a
      result, the refractive indices of these films increased with increasing relative
      humidity (RH). The dependence of the refractive index on RH was eliminated by
      treating the calcined films with trimethylchlorosilane.

PMID- 14664601
TI  - Isolation and characterization of nongeminal cyclic methylphenylphosphazene
      tetramers.
AB  - Heating pure samples of the cyclic phosphazenes, cis- or trans-[Me(Ph)PN](3),
      yielded mixtures of the cis and trans isomers of the cyclic phosphazene trimers,
      [Me(Ph)PN](3), and all four geometric isomers of the tetramers, [Me(Ph)PN](4).
      Varying the temperature and heating times changes the ratio of these components.
      Following the thermolysis by NMR spectroscopy indicated that only a mixture of
      the two isomeric trimers occurred initially. Longer heating times produced
      mixtures of the isomers of the tetramer. Column chromatography and solubility
      differences were used to separate each of the isomers of the tetramer.
      Spectroscopic and X-ray crystallographic studies suggest that the four different
      geometrical isomers of the tetramer can be described as cone, partial cone, 1,2
      alternate, and 1,3-alternate by analogy to calix[4]arene.

PMID- 14664602
TI  - Cluster-to-metal magnetic coupling: synthesis and characterization of 25-electron
      [Re6-nOsnSe8(CN)6](5-n)-(n = 1, 2) clusters and (Re6-nOsnSe8[CNCu(Me6tren)]6)9+(n
      = 0, 1, 2) assemblies.
AB  - The first face-capped octahedral clusters with 25 metal-based valence electrons
      are shown to provide versatile building units capable of engaging in magnetic
      exchange coupling. Reactions of [Re(5)OsSe(8)Cl(6)](3-) and
      [Re(4)Os(2)Se(8)Cl(6)](2-) with NaCN in a melt of NaNO(3) or KCF(3)SO(3) afford
      the 24-electron clusters [Re(5)OsSe(8)(CN)(6)](3-) and [Re(4)Os(2)Se(8)(CN)(6)](2
      ). The 13C NMR spectrum of a 13C-labeled version of the latter species indicates
      a 1:2 mixture of cis and trans isomers. Cyclic voltammograms of the clusters in
      acetonitrile display reversible [Re(5)OsSe(8)(CN)(6)](3-/4-), cis
      [Re(4)Os(2)Se(8)(CN)(6)](2-/3-), and trans-[Re(4)Os(2)Se(8)(CN)(6)](2-/3-)
      couples at E(1/2) = -1.843, -0.760, and -1.031 V vs FeCp(2)(0/+), respectively,
      in addition to other redox processes. Accordingly, reduction of
      [Re(5)OsSe(8)(CN)(6)](3-) with sodium amalgam and [Re(4)Os(2)Se(8)(CN)(6)](2-)
      with cobaltocene produces the 25-electron clusters [Re(5)OsSe(8)(CN)(6)](4-) and
      [Re(4)Os(2)Se(8)(CN)(6)](3-). EPR spectra of these S = 1/2 species in frozen DMF
      solutions exhibit isotropic signals with g = 1.46 for the monoosmium cluster and
      g = 1.74 and 1.09 for the respective cis and trans isomers of the diosmium
      cluster. In each case, results from DFT calculations show the unpaired spin to
      delocalize to some extent into the pi* orbitals of the cyanide ligands,
      suggesting the possibility of magnetic superexchange. Reaction of
      [Re(5)OsSe(8)(CN)(6)](3-) with [Ni(H(2)O)(6)](2+) in aqueous solution generates
      the porous Prussian blue analogue Ni(3)[Re(5)OsSe(8)(CN)(6)](2).32H(2)O; however,
      the tendency of the 25-electron clusters to oxidize in water prohibits their use
      in reactions of this type. Instead, a series of cyano-bridged assemblies, [Re(6
      n)Os(n)Se(8)[CNCu(Me(6)tren)](6)](9+) (n = 0, 1, 2; Me(6)tren = tris(2
      (dimethylamino)ethyl)amine), were synthesized to permit comparison of the
      exchange coupling abilities of clusters with 23-25 electrons. As expected, the
      results of magnetic susceptibility measurements show no evidence for exchange
      coupling in the assemblies containing the 23- and 24-electron clusters, but
      reveal the presence of weak ferromagnetic coupling in
      [Re(4)Os(2)Se(8)[CNCu(Me(6)tren)](6)](9+). Assuming all cluster-Cu(II) exchange
      interactions to be equivalent, the data were fit to give an estimated coupling
      strength of J = 0.4 cm(-1). To our knowledge, the ability of such clusters to
      participate in magnetic exchange coupling has never previously been demonstrated.

PMID- 14664603
TI  - Mixed-valent [FeIV(mu-O)(mu-carboxylato)2FeIII]3+ core.
AB  - The symmetrically ligated complexes 1, 2, and 3 with a (mu-oxo)bis(mu
      acetato)diferric core can be one-electron oxidized electrochemically or
      chemically with aminyl radical cations [*NR3][SbCl6] in acetonitrile yielding
      complexes which contain the mixed-valent [(mu-oxo)bis(mu
      acetato)iron(IV)iron(III)]3+ core: [([9]aneN3)(2FeIII2)(mu-O)(mu-CH3CO2)2](ClO4)2
      (1(ClO4)2), [(Me3[9]aneN3)(2FeIII2)(mu-O)(mu-CH3CO2)2](PF6)2 (2(PF6)(2)), and
      [(tpb)(2FeIII2)(mu-O)(mu-CH3CO2)2] (3) where ([9]aneN3) is the neutral triamine
      1,4,7-triazacyclononane and (Me3[9]aneN3) is its tris-N-methylated derivative,
      and (tpb)(-) is the monoanion trispyrazolylborate. The asymmetrically ligated
      complex [(Me3[9]aneN3)FeIII(mu-O)(mu-CH3CO2)2FeIII(tpb)](PF6) (4(PF6)) and its
      one-electron oxidized form [4ox]2+ have also been prepared. Finally, the known
      heterodinuclear species [(Me3[9]aneN3)CrIII(mu-O)(mu-CH3CO2)2Fe([9]aneN3)](PF6)2
      (5(PF6)(2)) can also be one-electron oxidized yielding [5ox]3+ containing an
      iron(IV) ion. The structure of 4(PF6).0.5CH3CN.0.25(C2H5)2O has been determined
      by X-ray crystallography and that of [5ox]2+ by Fe K-edge EXAFS-spectroscopy
      (Fe(IV)-O(oxo): 1.69(1) A; Fe(IV)-O(carboxylato) 1.93(3) A, Fe(IV)-N 2.00(2) A)
      contrasting the data for 5 (Fe(III)-O(oxo) 1.80 A; Fe(III)-O(carboxylato) 2.05 A,
      Fe-N 2.20 A). [5ox]2+ has an St = 1/2 ground state whereas all complexes
      containing the mixed-valent [FeIV(mu-O)(mu-CH3CO2)2FeIII]3+ core have an St = 3/2
      ground state. Mossbauer spectra of the oxidized forms of complexes clearly show
      the presence of low spin FeIV ions (isomer shift approximately 0.02 mm s(-1),
      quadrupole splitting approximately 1.4 mm s(-1) at 80 K), whereas the high spin
      FeIII ion exhibits delta approximately 0.46 mm s(-1) and DeltaE(Q) approximately
      0.5 mm s(-1). Mossbauer, EPR spectral and structural parameters have been
      calculated by density functional theoretical methods at the BP86 and B3LYP
      levels. The exchange coupling constant, J, for diiron complexes with the mixed
      valent FeIV-FeIII core (H = -2J S1.S2; S(1) = 5/2; S2 = 1) has been calculated to
      be -88 cm(-1) (intramolecular antiferromagnetic coupling) and for the reduced
      diferric form of -75 cm(-1) in reasonable agreement with experiment (J = -120 cm(
      1)).

PMID- 14664604
TI  - The primary photodynamics of aqueous nitrate: formation of peroxynitrite.
AB  - We have examined the photochemical reactions occurring after irradiation at 200
      nm of the aqueous nitrate ion, NO3(-)(aq). Using femtosecond transient absorption
      spectroscopy over the range 194-388 nm, we have characterized the formation and
      subsequent relaxation of the primary photoproducts of nitrate photolysis. The
      dominant photoproduct is the cis-isomer of peroxynitrite, which accounts for 48%
      of the excited state molecules initially produced. A slightly smaller fraction,
      44%, of the excited molecules return to the electronic ground state of NO3(-) and
      relax to the vibrational ground state in 2 ps. The remaining 8% of the molecules
      initially excited react via the *NO + *O2(-) or the NO- + O2 dissociation
      channels. Formation of NO2(-) and *NO2 is not observed, suggesting that the
      previous observations of these species in steady-state photolysis are caused by
      reactions occurring on a longer time scale.

PMID- 14664605
TI  - Continuous flow hydroformylation of alkenes in supercritical fluid-ionic liquid
      biphasic systems.
AB  - A process for the hydroformylation of relatively low volatility alkenes
      (demonstrated for 1-dodecene) in a continuous flow system is described. The
      catalyst is dissolved in an ionic liquid while the substrate and gaseous reagents
      are transported into the reactor dissolved in supercritical CO(2), which
      simultaneously acts as a transport vector for aldehyde products. Decompression of
      the fluid mixture downstream yields products which are free of both reaction
      solvent and catalyst. The use of rhodium complexes of triaryl phosphites leads to
      ligand degradation through reaction of the ionic liquid with water and subsequent
      attack of the released HF on the phosphite. Sodium salts of sulfonated phosphines
      are insufficiently soluble in the ionic liquids to obtain acceptable rates, but
      replacing the sodium by a cation similar to that derived from the ionic liquid,
      allows good solubility and activity to be obtained. The nature of the ionic
      liquid is very important in achieving high rates, with 1-alkyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)amides giving the best activity if
      the alkyl chain is at least C(8). Catalyst turnover frequencies as high as 500 h(
      1) have been observed, with the better rates at higher substrate flow rates.
      Rhodium leaching into the product stream can be as low as 0.012 ppm, except at
      low partial pressures of CO/H(2), when it is significantly higher. Oxygen
      impurities in the CO(2) feed can lead to oxidation of the phosphine giving higher
      rates, lower selectivities to the linear aldehyde, increased alkene isomerization
      and greater leaching of rhodium. However, it is found that under certain process
      conditions, the supercritical fluid-ionic liquid (SCF-IL) system can be operated
      continuously for several weeks without any visible sign of catalyst degradation.
      Comparisons with commercial hydroformylation processes are provided.

PMID- 14664606
TI  - Colloidal crystal films: advances in universality and perfection.
AB  - For three-dimensional photonic crystals, made either by top-down microfabrication
      or by bottom-up self-assembly approaches, to comply with the stringent
      requirements of optical telecommunication applications, their degree of
      structural perfection and optical quality must meet an exceptionally high
      standard. Only with such superior quality photonic crystals can their unique
      optical properties be harnessed in optical devices and circuits constructed from
      micrometer-sized optical components. In this paper, we present a new strategy for
      making silica colloidal crystal films with a sufficiently high level of
      structural perfection and optical quality to make it competitive as a practical
      route to photonic crystal optical components. The attainment of this goal takes
      due cognizance of three key synergistic factors in the film formation process.
      The first recognizes the necessity to prepare high-quality silica spheres, which
      are highly monodisperse, with a polydispersity index significantly better than
      2%, and the second recognizes that the population of spheres must be devoid of
      even the smallest fraction of substantially smaller or larger spheres or sphere
      doublets. The latter turns out to have a minimal effect on the polydispersity
      index, and yet a major detrimental effect on the overall structural order of the
      film. The third concerns the film-forming method itself, which necessitated the
      development of a novel process founded upon isothermal heating evaporation
      induced self-assembly (IHEISA) of spheres on a planar substrate. This new method
      has several advantages over previously reported ones. It is able to deposit very
      high-quality silica colloidal crystal film rapidly over large areas, with a
      controlled thickness and without any restrictions on sphere sizes.

PMID- 14664607
TI  - Electronic structure of 1 to 2 nm diameter silicon core/shell nanocrystals:
      surface chemistry, optical spectra, charge transfer, and doping.
AB  - Static and time-dependent density functional calculations, geometrically
      optimized and including all electrons, are described for silicon nanocrystals as
      large as Si(87)H(76), which contains 163 atoms. We explore and predict the effect
      that different sp(3) passivation schemes-F or H termination, thin oxide shell, or
      alkane termination-have on the HOMO and LUMO, on the optical spectra, and on
      electron transfer properties. Electronegativity comparisons are a useful guide in
      understanding the observed deviation from the simple quantum size effect model.
      Nanocrystals containing Al or P impurity atoms, either on the surface or in the
      interior, are explored to understand electrical doping in strongly quantum
      confined nanocrystals. Surface dangling bonds are found to participate in
      internal charge transfer with P atom dopant electrons.

PMID- 14664608
TI  - True stabilization energies for the optimal planar hydrogen-bonded and stacked
      structures of guanine...cytosine, adenine...thymine, and their 9- and 1-methyl
      derivatives: complete basis set calculations at the MP2 and CCSD(T) levels and
      comparison with experiment.
AB  - Planar H-bonded and stacked structures of guanine...cytosine (G.C),
      adenine...thymine (A...T), 9-methylguanine...1-methylcytosine (mG...mC), and 9
      methyladenine...1-methylthymine (mA...mT) were optimized at the RI-MP2 level
      using the TZVPP ([5s3p2d1f/3s2p1d]) basis set. Planar H-bonded structures of
      G...C, mG...mC, and A...T correspond to the Watson-Crick (WC) arrangement, in
      contrast to mA...mT for which the Hoogsteen (H) structure is found. Stabilization
      energies for all structures were determined as the sum of the complete basis set
      limit of MP2 energies and a (DeltaE(CCSD(T)) - DeltaE(MP2)) correction term
      evaluated with the cc-pVDZ(0.25,0.15) basis set. The complete basis set limit of
      MP2 energies was determined by two-point extrapolation using the aug-cc-pVXZ
      basis sets for X = D and T and X = T and Q. This procedure is required since the
      convergency of the MP2 interaction energy for the present complexes is rather
      slow, and it is thus important to include the extrapolation to the complete basis
      set limit. For the MP2/aug-cc-pVQZ level of theory, stabilization energies for
      all complexes studied are already very close to the complete basis set limit. The
      much cheaper D-->T extrapolation provided a complete basis set limit close (by
      less than 0.7 kcal/mol) to the more accurate T-->Q term, and the D-->T
      extrapolation can be recommended for evaluation of complete basis set limits of
      more extended complexes (e.g. larger motifs of DNA). The convergency of the
      (DeltaE(CCSD(T)) - DeltaE(MP2)) term is known to be faster than that of the MP2
      or CCSD(T) correlation energy itself, and the cc-pVDZ(0.25,0.15) basis set
      provides reasonable values for planar H-bonded as well as stacked structures.
      Inclusion of the CCSD(T) correction is essential for obtaining reliable relative
      values for planar H-bonding and stacking interactions; neglecting the CCSD(T)
      correction results in very considerable errors between 2.5 and 3.4 kcal/mol.
      Final stabilization energies (kcal/mol) for the base pairs studied are very
      substantial (A...T WC, 15.4; mA...mT H, 16.3; A...T stacked, 11.6; mA...mT
      stacked, 13.1; G...C WC, 28.8; mG...mC WC, 28.5; G...C stacked, 16.9; mG...mC
      stacked, 18.0), much larger than published previously. On the basis of comparison
      with experimental data, we conclude that our values represent the lower boundary
      of the true stabilization energies. On the basis of error analysis, we expect the
      present H-bonding energies to be fairly close to the true values, while stacked
      energies are still expected to be about 10% too low. The stacking energy for the
      mG...mC pair is considerably lower than the respective H-bonding energy, but it
      is larger than the mA...mT H-bonding energy. This conclusion could significantly
      change the present view on the importance of specific H-bonding interactions and
      nonspecific stacking interactions in nature, for instance, in DNA. Present
      stabilization energies for H-bonding and stacking energies represent the most
      accurate and reliable values and can be considered as new reference data.

PMID- 14664609
TI  - Characterization of hydrogen bonds in the interactions between the hydroperoxyl
      radical and organic acids.
AB  - The hydrogen bonds formed between the hydroperoxyl radical and formic, acetic,
      and trifluoroacetic acids were characterized using geometric, energetic, and
      electronic parameters through calculations done with the UB3LYP/6-311++G
      (3df,3pd) and UB3LYP/EPR-III methods. The wave functions were analyzed through
      the natural bond orbital, natural steric analysis, natural resonance theory, and
      atoms in molecules methods. The energy decomposition method proposed by Xantheas
      was used. The vibrational frequencies and the intensity of the O-H stretching
      bands, as well as the spin densities, were compared with experimental evidence.
      The results allowed the characterization of the hydrogen bonds formed in the
      complexation of the acids with the hydroperoxyl radical. Complexation led to
      significant alterations in the equilibrium geometry of the monomers. Energetic
      analysis proved that the studied complexes are stable and allowed the
      understanding of the effect of the electron-donating and electron-withdrawing
      groups in their stabilization. The alterations in the electronic structure of the
      monomers after complexation led to an increase in the resonance of the carboxyl
      group, which can be partially attributed to the hydrogen bond.

PMID- 14664610
TI  - 13C-13C rotational resonance width distance measurements in uniformly 13C-labeled
      peptides.
AB  - The rotational resonance width (R2W) experiment is a constant-time version of the
      rotational resonance (R2) experiment, in which the magnetization exchange is
      measured as a function of sample spinning frequency rather than the mixing time.
      The significant advantage of this experiment over conventional R2 is that both
      the dipolar coupling and the relaxation parameters can be independently and
      unambiguously extracted from the magnetization exchange profile. In this paper,
      we combine R2W with two-dimensional 13C-13C chemical shift correlation
      spectroscopy and demonstrate the utility of this technique for the site-specific
      measurement of multiple 13C-13C distances in uniformly labeled solids. The
      dipolar truncation effects, usually associated with distance measurements in
      uniformly labeled solids, are considerably attenuated in R2W experiments. Thus,
      R2W experiments are applicable to uniformly labeled biological systems. To
      validate this statement, multiple 13C-13C distances (in the range of 3-6 A) were
      determined in N-acetyl-[U-13C,15N]l-Val-l-Leu with an average precision of +/-0.5
      A. Furthermore, the distance constraints extracted using a two-spin model agree
      well with the X-ray crystallographic data.

PMID- 14664611
TI  - Probing the mechanism of aqueous two-phase system formation for alpha-elastin on
      chip.
AB  - The kinetics of formation of the aqueous two-phase system (ATPS) for alpha
      elastin was studied by dark field microscopy in an on-chip linear temperature
      gradient. Scattering intensities of protein solutions were recorded as a function
      of temperature and time, simultaneously at several concentrations. It was found
      that the formation rate of the ATPS could be fit as a first-order process and
      that the apparent rate constant increased with protein concentration. The
      activation energy for the process was 9.5 +/- 0.5 kcal/mol, and this result was
      consistent with a coalescence mechanism. Experiments were also conducted with
      varying concentrations of sodium dodecyl sulfate, which shut off the coalescence
      mechanism forcing ATPS formation to proceed through Ostwald ripening. When this
      was done, the activation energy increased to 33 +/- 2 kcal/mol and the kinetics
      became consistent with a second-order process.

PMID- 14664612
TI  - Excited-state metal-to-ligand charge transfer dynamics of a ruthenium(II) dye in
      solution and adsorbed on TiO2 nanoparticles from resonance Raman spectroscopy.
AB  - The dynamics of metal-to-ligand charge transfer (MLCT) in a cis-bis(4,4'
      dicarboxy-2,2'-bipyridine)-bis(isothiocyanato)ruthenium(II) dye (N3) are compared
      for the free dye in solution and the dye adsorbed on the surface of the TiO(2)
      nanoparticles from resonance Raman spectroscopy. The 544-nm MLCT absorption band
      of N3 adsorbed on TiO(2) is slightly blue-shifted from that of the free N3,
      indicating a weak electronic coupling between N3 and TiO(2). The resonance Raman
      spectra of N3 and the N3|TiO(2) complex obtained upon excitation within the
      lowest-lying MLCT singlet state of the dye are similar except for slight shifts
      in band positions. Resonance Raman cross sections have been obtained for the
      vibrational modes of both N3 and N3|TiO(2) with excitation frequencies spanning
      the 544-nm MLCT band. Self-consistent analysis of the resulting resonance Raman
      excitation profiles and absorption spectrum using a time-dependent wave packet
      formalism over two electronic states yields mode-specific vibrational and solvent
      reorganization energies. Despite the weak electronic coupling between N3 and
      TiO(2) in N3|TiO(2), adsorption strongly affects the reorganization energies of
      N3 in the intramolecular MLCT state. Adsorption of N3 onto TiO(2) increases the
      absolute Raman cross section of each mode by a factor of ca. 1.6 and decreases
      the vibrational and solvent reorganization energies by factors of 2 and 6,
      respectively. The excited-state dynamics of N3 adsorbed on the surface of TiO(2)
      nanoparticles were observed to be independent of the number of N3 molecules
      adsorbed per TiO(2) nanoparticle. The effect of TiO(2) on the dynamics of the
      adsorbed N3 is primarily due to both mode-specific vibrational and electronic
      pure dephasing, with the dominant contribution from the latter process.

PMID- 14664613
TI  - On the origin of residual dipolar couplings from denatured proteins.
AB  - Effects of steric obstruction on random flight chains are examined. Spatial
      probability distributions are elaborated to calculate residual dipolar couplings
      and residual chemical shift anisotropy, parameters that are acquired by NMR
      spectroscopy from solutes dissolved in dilute liquid crystals. Calculations yield
      chain length and residue position-dependent values in good agreement with
      simulations to provide understanding of recently acquired data from denatured
      proteins.

PMID- 14664614
TI  - Origin of high second- and third-order nonlinear optical response in
      ammonio/borato diphenylpolyene zwitterions: the remarkable role of polarized
      aromatic groups.
AB  - We present a quantum-chemical analysis of the molecular structure and second- and
      third-order polarizabilities in a series of promising nonlinear optical (NLO)
      chromophores, the zwitterionic ammonio/borato diphenylpolyenes, R3N+Ph(C=C)nPhB
      R3, whose synthesis has been reported recently. The molecular geometries are
      obtained via MP2/6-31G optimization, while the NLO properties are calculated with
      the INDO Hamiltonian using the sum-over-states and finite-field real-space
      methods. The real-space approach allows the direct evaluation of the NLO-active
      segments of the molecules, while the sum-over-states results illustrate the
      virtual excitations and charge-transfer pathways that are essential in the NLO
      response. Both methods highlight the remarkable and unexpected result that it is
      the strongly polarized phenylene groups that play the key role in generating a
      high NLO response.

PMID- 14664615
TI  - Remarkable solvent-dependent excited-state chirality: a molecular modulator of
      circularly polarized luminescence.
AB  - The photochemical control of ground- and excited-state chirality of (M)-cis-(1)
      and (P)-trans-(2)-2-nitro-7-(dimethylamino)-9-(2',3'-dihydro-1'H-naphtho[2,1-b]
      thiopyran-1'-ylidene)-9H-thioxanthene is described. It is shown that while ground
      state chirality can be controlled photochemically by irradiation with light of
      different wavelengths, the excited state chirality can be tuned either
      photochemically in a similar way or by appropriate choice of solvent. In benzene
      solution, circularly polarized luminescence of the two isomers with opposite
      ground-state helicity, (M)-cis-1 and (P)-trans-2, revealed corresponding excited
      states of opposite helicity. On the contrary, in n-hexane solution, circularly
      polarized luminescence was identical for the two forms indicating identical
      excited state chirality. Circularly polarized luminescence (CPL), steady-state
      and time-dependent fluorescence, and time-resolved microwave conductivity (TRMC)
      measurements in both n-hexane and benzene are reported, which provide an
      explanation for the remarkable solvent dependence of excited-state chirality.

PMID- 14664616
TI  - Unusual salt stability in highly charged diblock co-polypeptide hydrogels.
AB  - The stability and properties of dilute solution hydrogels, synthesized by
      transition metal mediated polymerization of amino acid N-carboxyanhydrides
      (NCAs), have been studied in deionized (DI) water as well as various ionic media.
      These hydrogels are diblock amphiphilic copolymers of hydrophilic, charged
      segments of poly(l-lysine HBr) or poly(l-glutamic acid sodium salt), and helical,
      hydrophobic segments of poly(l-leucine). While many of these samples are able to
      form strong gels in deionized water at polymer concentrations as low as 0.25 wt
      %, stability in salt or buffer solutions was found to be only achieved at
      moderately higher polymer concentrations ( approximately 3.0 wt %). We have
      adjusted relative copolymer compositions and molecular weights to optimize
      hydrogel strength and polymer solubility in salt concentrations up to 0.5 M NaCl,
      as well as in cell growth media and aqueous buffers of varying pH. These
      materials are unique since they do not collapse in high ionic strength media,
      even though gel formation is contingent upon the presence of highly charged
      polyelectrolyte segments. The remarkable properties of these hydrogels make them
      excellent candidates for use as scaffolds in biomedical applications, such as
      tissue regeneration.

PMID- 14664617
TI  - Ion solvation thermodynamics from simulation with a polarizable force field.
AB  - Thermodynamic measurements of the solvation of salts and electrolytes are
      relatively straightforward, but it is not possible to separate total solvation
      free energies into distinct cation and anion contributions without reference to
      an additional extrathermodynamic assumption. The present work attempts to resolve
      this difficulty using molecular dynamics simulations with the AMOEBA polarizable
      force field and perturbation techniques to directly compute absolute solvation
      free energies for potassium, sodium, and chloride ions in liquid water and
      formamide. Corresponding calculations are also performed with two widely used
      nonpolarizable force fields. The simulations with the polarizable force field
      accurately reproduce in vacuo quantum mechanical results, experimental ion
      cluster solvation enthalpies, and experimental solvation free energies for whole
      salts, while the other force fields do not. The results indicate that
      calculations with a polarizable force field can capture the thermodynamics of ion
      solvation and that the solvation free energies of the individual ions differ by
      several kilocalories from commonly cited values.

PMID- 14664619
TI  - Introduction: Atmospheric chemistry--long-term issues.

PMID- 14664620
TI  - Large-scale atmospheric dynamics for atmospheric chemists.

PMID- 14664621
TI  - Chemical kinetics and atmospheric chemistry: role of data evaluation.

PMID- 14664622
TI  - Laboratory studies of atmospheric reactions at low temperatures.

PMID- 14664623
TI  - Toward a quantitative analysis of association reactions in the atmosphere.

PMID- 14664624
TI  - Master equation analysis of pressure-dependent atmospheric reactions.

PMID- 14664626
TI  - Atmospheric degradation of volatile organic compounds.

PMID- 14664625
TI  - Reaction barriers: origin and evolution.

PMID- 14664627
TI  - Kinetics of halogen oxide radicals in the stratosphere.

PMID- 14664628
TI  - The atmospheric chemistry of alkoxy radicals.

PMID- 14664629
TI  - Kinetics of aqueous phase reactions relevant for atmospheric chemistry.

PMID- 14664630
TI  - Atmospheric photochemistry via vibrational overtone absorption.

PMID- 14664631
TI  - Energetic oxygen in the upper atmosphere and the laboratory.

PMID- 14664632
TI  - Photolysis of atmospheric ozone in the ultraviolet region.

PMID- 14664633
TI  - Interactions of atmospheric trace gases with ice surfaces: adsorption and
      reaction.

PMID- 14664634
TI  - The tropospheric chemistry of sea salt: a molecular-level view of the chemistry
      of NaCl and NaBr.

PMID- 14664635
TI  - Heterogeneous reactions on salts.

PMID- 14664636
TI  - Reactions on mineral dust.

PMID- 14664637
TI  - Abundant oxygenates in the atmosphere: a biochemical perspective.

PMID- 14664638
TI  - Iodine in the marine boundary layer.

PMID- 14664639
TI  - Atmospheric chemistry of meteoric metals.

PMID- 14664640
TI  - Photochemistry of NO2 in Earth's stratosphere: constraints from observations.

PMID- 14664641
TI  - Atmospheric chemistry of alternative fuels and alternative chlorofluorocarbons.

PMID- 14664642
TI  - Isotopes of volatile organic compounds: an emerging approach for studying
      atmospheric budgets and chemistry.

PMID- 14664643
TI  - Determination of atmospheric lifetimes via the measurement of OH radical
      kinetics.

PMID- 14664644
TI  - Kinetics and mechanisms of the oxidation of oxygenated organic compounds in the
      gas phase.

PMID- 14664645
TI  - Laboratory perspectives on the chemical transformations of organic matter in
      atmospheric particles.

PMID- 14664646
TI  - Isotope effects in the chemistry of atmospheric trace compounds.

PMID- 14664647
TI  - Measurement of OH and HO2 in the troposphere.

PMID- 14664648
TI  - Measurements of peroxides and what they tell us.

PMID- 14664650
TI  - Broad-band cavity ring-down spectroscopy.

PMID- 14664649
TI  - Absorption spectroscopy in high-finesse cavities for atmospheric studies.

PMID- 14664651
TI  - What is the role of NSAIDs in pre-emptive analgesia?
AB  - NSAIDs inhibit the cyclo-oxygenase enzymes, and decrease peripheral and central
      prostaglandin production. In addition to reducing the inflammation that
      accompanies tissue injury, decreasing prostaglandin production attenuates the
      response of the peripheral and central components of the nervous system to
      noxious stimuli. Such a reduction in the response to pain can reduce the
      peripheral and central sensitisation induced by noxious stimuli, and reduce the
      pain experienced in response to subsequent noxious stimuli. These properties
      would seem to make NSAIDs ideal drugs to use in a pre-emptive fashion, where
      analgesics are administered prior to a noxious stimulus, such as surgery, with
      the expectation that reduction in peripheral and central sensitisation will lead
      to a decrease of pain.However, the available perioperative trials of pre-emptive
      NSAID use have yielded modest or equivocal results, and these may be due, in
      part, to controversy associated with the definition of pre-emptive analgesia and
      how to conduct the corresponding clinical trials. Although NSAIDs may have a
      limited ability by themselves to induce a pre-emptive analgesic effect, the
      available trials suggest how the perioperative use of these drugs may be made
      more effective. It is expected that NSAIDs will play an increasing role in
      multimodal analgesia and pain relief in general.

PMID- 14664652
TI  - Excessive daytime sleepiness and sleep disturbances in patients with neurological
      diseases: epidemiology and management.
AB  - Up to 12% of the general population experience excessive daytime sleepiness
      (EDS), with increasing prevalence in the elderly. EDS may lead to cognitive
      impairment, resulting in inattentiveness, poor memory, mood disorders and an
      increased risk of accidents. As a result, quality of life is reduced in most
      patients with EDS as well as in their caregiving spouses. There are a variety of
      causes leading to EDS, including CNS pathology, neurological dysfunction,
      associated sleep disorders with insufficient or fragmented sleep, and drug
      therapy. Since EDS accompanies many neurological disorders, such as
      neurodegenerative and neuromuscular diseases, neurologists should be familiar
      with the diagnosis, its major causes and with treatment options. The main focus
      of this article is on movement disorders, neuromuscular diseases, multiple
      sclerosis, dementia, cerebrovascular diseases, head and brain trauma, pain and
      epilepsy. General management strategies for EDS in all these neurological
      diseases include sleep hygiene aspects such as extensions of noctural time in bed
      and frequent naps during the day. Pharmacological treatment is generally achieved
      with stimulants such as amphetamine, methylphenidate and pemoline, or newer
      compounds such as modafinil.

PMID- 14664653
TI  - Clinical pharmacology of proton pump inhibitors: what the practising physician
      needs to know.
AB  - Proton pump inhibitors (PPIs) [omeprazole, lansoprazole, pantoprazole,
      rabeprazole and esomeprazole] are widely utilised for the treatment of gastro
      oesophageal reflux disease, as well as other acid-related disorders. All PPIs
      suppress gastric acid secretion by blocking the gastric acid pump, H(+)/K(+)
      adenosine triphosphatase (ATPase), but the physicochemical properties of these
      drugs result in variations in the degree of acid suppression, as well as the
      speed of onset of acid inhibition. Such differences may impact on the clinical
      performance of PPIs, and this manuscript discusses data that may help clinicians
      choose between the available PPIs for specific clinical situations and
      indications. The characteristics of PPIs that have been developed subsequent to
      omeprazole offer several advantages over this prototype PPI, particularly with
      respect to the onset of acid suppression and reduced potential for inter
      individual pharmacokinetic variation and drug interactions. Newer agents inhibit
      H(+)/K(+)-ATPase more rapidly than omeprazole and emerging clinical data support
      potential clinical benefits resulting from this pharmacological property.
      Although key pharmacokinetic parameters (time to maximum plasma concentration and
      elimination half-life) do not differ significantly among PPIs, differences in the
      hepatic metabolism of these drugs can produce inter-patient variability in acid
      suppression, in the potential for pharmacokinetic drug interactions and, quite
      possibly, in clinical efficacy. All PPIs undergo significant hepatic metabolism.
      Because there is no direct toxicity from PPIs, there is minimal risk from the
      administration of any of them - even to patients with significant renal or
      hepatic impairment. However, there are significant genetic polymorphisms for one
      of the cytochrome P450 (CYP) isoenzymes involved in PPI metabolism (CYP2C19), and
      this polymorphism has been shown to substantially increase plasma levels of
      omeprazole, lansoprazole and pantoprazole, but not those of rabeprazole. Hepatic
      metabolism is also a key determinant of the potential for a given drug to be
      involved in clinically significant pharmacokinetic drug interactions. Omeprazole
      has the highest risk for such interactions among PPIs, and rabeprazole and
      pantoprazole appear to have the lowest risk.Thus, whereas all PPIs have been
      shown to be generally effective and safely used for the treatment of acid
      mediated disorders, there are chemical, pharmacodynamic and pharmacokinetic
      differences among these drugs that may make certain ones more, or less, suitable
      for treating different patient subgroups. Of course, the absolute magnitude of
      risk from any PPI in terms of drug-drug interactions is probably low - excepting
      interactions occurring as class effects related to acid suppression (e.g.
      increased digoxin absorption or inability to absorb ketoconazole).

PMID- 14664654
TI  - Enfuvirtide.
AB  - Enfuvirtide is the first of a new class of drugs, the fusion inhibitors. It is a
      synthetic peptide which binds to the HIV glycoprotein 41 (gp41), blocking fusion
      of the viral and cellular membranes. HIV isolates with reduced susceptibility to
      enfuvirtide have been recovered from patients receiving enfuvirtide in
      combination with other antiretroviral agents. Enfuvirtide 90mg (subcutaneously,
      twice daily) in combination with optimised background (OB) antiretroviral therapy
      significantly reduced plasma HIV RNA levels compared with OB alone after
      treatment for 24 weeks in two randomised trials involving adults with advanced
      HIV infection. The antiviral efficacy of enfuvirtide was maintained through to 48
      weeks. At 24 and 48 weeks, the increase from baseline in the CD4+ cell count was
      significantly greater for patients receiving enfuvirtide plus OB than for those
      receiving OB alone. Enfuvirtide 30 mg/m(2) or 60 mg/m(2) in combination with
      other antiretroviral agents reduced plasma HIV RNA levels and increased CD4+ cell
      counts in a small trial involving paediatric patients with HIV infection. Local
      injection-site reactions were common. Lymphadenopathy and pneumonia occurred more
      often in patients receiving enfuvirtide plus OB than in the control group. The
      incidence of most other events was similar in each group.

PMID- 14664659
TI  - Retrospective drug utilization review: incidence of clinically relevant potential
      drug-drug interactions in a large ambulatory population.
AB  - OBJECTIVE: To determine the incidence of clinically relevant potential drug-drug
      interactions (DDIs) in a large population of ambulatory patients utilizing a
      computerized, retrospective drug utilization review (DUR) program followed by
      clinical pharmacist audit. METHODS: The drug claims database included
      approximately 2.9 million patients with more than 30 million prescriptions
      dispensed in the 12-month period from September 2001 through August 2002. Cases
      were identified by a computerized, retrospective DUR program with embedded
      triggers to detect 69 prespecified potentially serious DDIs, with "serious"
      defined as an interaction that would likely require a change in therapy or use of
      additional clinical or laboratory monitoring. Two types of automated,
      computerized assessments were conducted: the first simply detected coprescribed
      drug pairs, and the second assessment used more sophisticated filters to reduce
      false positive alerts for coprescribed drug pairs. Clinical pharmacist audit then
      determined the final incidence of clinically relevant warnings; in this audit,
      coprescribed drug pairs were defined as clinically relevant if they could cause
      potentially serious DDIs. RESULTS: Eighteen drug pairs had insufficient cases for
      inclusion, leaving 51 drug pairs for evaluation. A total of 244,703 cases of
      potential DDIs were identified (0.8% of total prescription claims) by simple
      automated screens. More sophisticated DDI filters reduced the 244,703 potential
      DDIs by 70.8%, to a total of 65,544 pairs (0.2% of total prescription claims).
      Clinical pharmacist review reduced the number of potential DDIs by an additional
      80.6%, to 12,722 drug pairs (0.04% of total prescription claims) deemed
      clinically relevant. The combination of sophisticated DDI filters and clinical
      pharmacist review reduced the incidence of potentially serious DDIs by 94.3%.
      CONCLUSION: The incidence of potentially serious DDIs is relatively low (less
      than 1%) among ambulatory patients; however, the incidence depends on the method
      of case finding. Retrospective DUR programs, especially those with additional
      automated filters or that utilize additional pharmacist review, appear to be
      important screening tools in determining true rates of coprescribed drug pairs
      that can lead to potentially serious DDIs.

PMID- 14664660
TI  - Financial risk relationships and adoption of management strategies in physician
      groups for self-administered injectable drugs.
AB  - OBJECTIVE: To consider the extent, nature, and range of risk arrangements between
      physician groups and health maintenance organizations (HMOs) for self
      administered injectable (SAI) drugs; to examine types and frequencies of SAI drug
      use management strategies adopted by physician groups; and to explore the
      relationship between locus and level of financial risk for SAIs and physician
      group strategy adoption. METHODS: We used a multiple case-study design to select
      physician groups and their health maintenance organization (HMO) contractual
      partners in 4 markets in the United States (Northwest, Northeast, Midwest,
      Southwest). Physician groups in these markets were chosen based on size (e50
      physicians) and experience with drug risk (e1 year). Physician groups were asked
      to identify their 3 major HMO contractual partners in each market. Telephone
      interviews were conducted from January 2000 to June 2001, with the resulting
      purposive sample of 37 individuals representing 20 physician groups. RESULTS: We
      found that the level and locus of SAI financial risk were related to the adoption
      of management strategies. Physician groups with higher financial risk for SAIs
      adopted more strategies than lower-risk groups. Groups with SAI financial risk in
      the medical services capitation (MSC) adopted 9.2 strategies per group. In
      contrast, groups with SAI financial risk in the pharmacy-risk budget (PRB)
      averaged 1.5 strategies per group. Groups with SAI financial risk in both the MSC
      and PRB fell in-between, averaging 4.5 strategies per group. The most frequently
      adopted strategy was designing evidenced-based therapeutic guidelines, i.e.,
      protocols based on evidence from the peer-reviewed literature used to guide
      physicians in the treatment of typically chronic conditions (9 groups, 45% of
      sample). The second most common strategy involved adapting the existing
      utilization management system to process SAIs (7 groups, 35%) and the
      establishment of office procedures for internal authorization (5 groups, 25%).
      The least frequently used strategies were determining amount paid to out-of-group
      physician providers (1 group, 5%) and hiring personnel (e.g., pharmacists) in
      claims or utilization management departments to implement and manage SAI programs
      (1 group, 5%). We also identified potential factors that increased the likelihood
      of strategy adoption and that could slow the rate of SAI cost increases.
      CONCLUSION: Our findings suggest that adoption of SAI drug-use management
      strategies may be more likely to occur when there is a minimum level of risk for
      SAI drug costs. Likewise, both the adoption of strategies and the opportunity to
      slow the rate of SAI cost increases may be more likely to occur when 3 additional
      factors are present: a contractual environment conducive to controlling SAI drug
      costs, the ability to implement SAI drug-use management strategies, and power in
      negotiations with drug manufacturers to reduce SAI prices. A sustainable and
      affordable SAI financial risk management program maximizing these factors while
      minimizing the financial burden for patients will require collaboration among all
      stakeholders, payers, providers, drug manufacturers, and patients.

PMID- 14664657
TI  - Levofloxacin: a review of its use in the treatment of bacterial infections in the
      United States.
AB  - Levofloxacin (Levaquin) is a fluoroquinolone antibacterial agent with a broad
      spectrum of activity against Gram-positive and Gram-negative bacteria and
      atypical respiratory pathogens. It is active against both penicillin-susceptible
      and penicillin-resistant Streptococcus pneumoniae. The prevalence of S.
      pneumoniae resistance to levofloxacin is <1% overall in the US.A number of
      randomised comparative trials in the US have demonstrated the efficacy of
      levofloxacin in the treatment of infections of the respiratory tract,
      genitourinary tract, skin and skin structures. Sequential intravenous to oral
      levofloxacin 750mg once daily for 7-14 days was as effective in the treatment of
      nosocomial pneumonia as intravenous imipenem/cilastatin 500-1000mg every 6-8
      hours followed by oral ciprofloxacin 750mg twice daily in one study. In patients
      with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral
      levofloxacin 500mg once daily for 7-14 days achieved clinical and bacteriological
      response rates similar to those with comparator agents, including
      amoxicillin/clavulanic acid, clarithromycin, azithromycin, ceftriaxone and/or
      cefuroxime axetil and gatifloxacin. A recent study indicates that intravenous or
      oral levofloxacin 750mg once daily for 5 days is as effective as 500mg once daily
      for 10 days, in the treatment of mild to severe CAP. Exacerbations of chronic
      bronchitis and acute maxillary sinusitis respond well to treatment with oral
      levofloxacin 500mg once daily for 7 and 10-14 days, respectively. Oral
      levofloxacin was as effective as ofloxacin in uncomplicated urinary tract
      infections and ciprofloxacin or lomefloxacin in complicated urinary tract
      infections. In men with chronic bacterial prostatitis treated for 28 days, oral
      levofloxacin 500mg once daily achieved similar clinical and bacteriological
      response rates to oral ciprofloxacin 500mg twice daily. Uncomplicated skin
      infections responded well to oral levofloxacin 500mg once daily for 7-10 days,
      while in complicated skin infections intravenous and/or oral levofloxacin 750mg
      for 7-14 days was at least as effective as intravenous ticarcillin/clavulanic
      acid (+/- switch to oral amoxicillin/clavulanic acid) administered for the same
      duration. Levofloxacin is generally well tolerated, with the most frequently
      reported adverse events being nausea and diarrhoea; in comparison with some other
      quinolones it has a low photosensitising potential and clinically significant
      cardiac and hepatic adverse events are rare. CONCLUSION: Levofloxacin is a broad
      spectrum antibacterial agent with activity against a range of Gram-positive and
      Gram-negative bacteria and atypical organisms. It provides clinical and
      bacteriological efficacy in a range of infections, including those caused by both
      penicillin-susceptible and -resistant strains of S. pneumoniae. Levofloxacin is
      well tolerated, and is associated with few of the phototoxic, cardiac or hepatic
      adverse events seen with some other quinolones. It also has a pharmacokinetic
      profile that is compatible with once-daily administration and allows for
      sequential intravenous to oral therapy. The recent approvals in the US for use in
      the treatment of nosocomial pneumonia and chronic bacterial prostatitis, and the
      introduction of a short-course, high-dose regimen for use in CAP, further extend
      the role of levofloxacin in treating bacterial infections.

PMID- 14664658
TI  - Basiliximab: a review of its use as induction therapy in renal transplantation.
AB  - Basiliximab (Simulect), a chimeric (human/murine) monoclonal antibody, is
      indicated for the prevention of acute organ rejection in adult and paediatric
      renal transplant recipients in combination with other immunosuppressive agents.
      Basiliximab significantly reduced acute rejection compared with placebo in renal
      transplant recipients receiving dual- (cyclosporin microemulsion and
      corticosteroids) or triple-immunotherapy (azathioprine- or mycophenolate mofetil
      based); graft and patient survival rates at 12 months were similar. Significantly
      more basiliximab than placebo recipients were free from the combined endpoint of
      death, graft loss or acute rejection 3 years, but not 5 years, after
      transplantation. The incidence of adverse events was similar in basiliximab and
      placebo recipients, with no increase in the incidence of infection, including
      cytomegalovirus (CMV) infection. Malignancies or post-transplant
      lymphoproliferative disorders after treatment with basiliximab were rare, with a
      similar incidence to that seen with placebo at 12 months or 5 years post
      transplantation. Rare cases of hypersensitivity reactions to basiliximab have
      been reported. The efficacy of basiliximab was similar to that of equine
      antithymocyte globulin (ATG) and daclizumab, and similar to or greater than that
      of muromonab CD3. Basiliximab was as effective as rabbit antithymocyte globulin
      (RATG) in patients at relatively low risk of acute rejection, but less effective
      in high-risk patients. Numerically or significantly fewer patients receiving
      basiliximab experienced adverse events considered to be related to the study drug
      than ATG or RATG recipients. The incidence of infection, including CMV infection,
      was similar with basiliximab and ATG or RATG. Basiliximab plus baseline
      immunosuppression resulted in no significant differences in acute rejection rates
      compared with baseline immunosuppression with or without ATG or antilymphocyte
      globulin in retrospective analyses conducted for small numbers of paediatric
      patients. Limited data from paediatric renal transplant recipients suggest a
      similar tolerability profile to that in adults. Basiliximab appears to allow the
      withdrawal of corticosteroids or the use of corticosteroid-free or calcineurin
      inhibitor-sparing regimens in renal transplant recipients. Basiliximab did not
      increase the overall costs of therapy in pharmacoeconomic studies. CONCLUSION:
      Basiliximab reduces acute rejection without increasing the incidence of adverse
      events, including infection and malignancy, in renal transplant recipients when
      combined with standard dual- or triple-immunotherapy. The overall incidence of
      death, graft loss or acute rejection was significantly reduced at 3 years; there
      was no significant difference for this endpoint 5 years after transplantation.
      Malignancy was not increased at 5 years. The overall efficacy, tolerability, ease
      of administration and cost effectiveness of basiliximab make it an attractive
      option for the prophylaxis of acute renal transplant rejection.

PMID- 14664661
TI  - Unmet needs in the treatment of allergic asthma: potential role of novel biologic
      therapies.
AB  - OBJECTIVE: To provide a review of the current status of the treatment of asthma
      and introduce new and developing forms of therapy by means of a review of
      published literature on asthma and publications on new and emerging therapies.
      Increased public awareness of asthma, improved patient and provider education,
      implementation of national treatment guidelines, and availability of safe and
      effective therapies have combined to provide an effective response to the
      increase in asthma prevalence. However, the number of persons with poorly
      controlled asthma and asthma-related complications remains unacceptably high.
      This is particularly true for the relatively small cohort of patients with
      moderateto- severe asthma that is poorly controlled with inhaled corticosteroids
      and other standard-of-care medications. Consequently, these patients often
      experience frequent exacerbations, leading to a disproportionate consumption of
      asthma health care resources and a poor quality of life. The National Committee
      on Quality Assurance suggests that the negative impact of asthma can be minimized
      if health care providers implement aggressive asthma management programs that
      include patient education and appropriate medications. Newer therapies such as
      injectable anti-IgE may provide a benefit for many patients. SUMMARY: Currently
      available asthma medications have been proven to be generally safe and effective
      for most asthma patients. However, the subset of patients with difficult-to-treat
      asthma who experience frequent exacerbations requiring emergency department
      visits or hospitalizations may benefit from novel therapies designed to target
      specific mechanisms underlying airway inflammation. CONCLUSIONS: New therapies
      may help in the treatment of patients whose asthma is not controlled. These
      include anti-immunoglobulin E (IgE) antibodies, cytokine modulators, and DNA
      vaccinations. Future research will determine if these targeted biologic therapies
      are a cost-effective means to improve the clinical and economic outcomes of
      asthma management.

PMID- 14664662
TI  - Determinants of the cost-effectiveness of statins.
AB  - OBJECTIVE: To examine the cost-effectiveness of statins in relation to different
      measures of effectiveness, differences in efficacy among individual statins, and
      the risk of coronary heart disease. Efficacy is defined here as the magnitude of
      the effect produced by a given amount of drug, as demonstrated in placebocontrol
      trials; i.e., the effectiveness per unit dose. DATA SYNTHESIS: Treatment
      guidelines categorize patients by their risk of coronary events and set lower
      target cholesterol levels for patients at higher risk. Statins vary in their
      efficacy. If effectiveness is expressed as percent lowering in low-density
      lipoprotein cholesterol (LDL-C) and relatively little cholesterol lowering is
      required.as in low-risk patients.even statins of low efficacy provide adequate
      cholesterol lowering, and drug price is the determining factor of
      costeffectiveness. For patients at high risk.the primary target group, which has
      been expanded in recent guidelines.high-efficacy statins are required to meet the
      more aggressive cholesterol goals, and efficacy is the important determinant of
      cost-effectiveness. When effectiveness is expressed in terms of life-years saved,
      the cost-effectiveness of statins as a class for treatment of high-risk patients
      compares favorably with the cost-effectiveness of generally accepted medical
      treatments. CONCLUSION: In order to optimize cost-effectiveness, the level of
      effectiveness required to treat the specific patient or patient group must be
      considered. Statin efficacy is the major determinant of cost-effectiveness when
      greater cholesterol lowering is required, i.e., for high-risk patients, who make
      up the primary target group. Statin price is the more important factor if only
      limited cholesterol lowering (e.g., 35% or less reduction in LDL) is required.

PMID- 14664663
TI  - Longitudinal assessment of a diabetes care management system in an integrated
      health network.
AB  - OBJECTIVE: To describe the results of longitudinal assessment of the results of a
      disease management process developed in a large integrated health care system
      that successfully improved care for patients with diabetes. Outcome measures
      included rates of testing of hemoglobin A1c (HbA1c) and low-density lipoprotein
      (LDL), rate of annual eye exams, and LDL and HbA1c values. METHODS: Intermountain
      Health Care (IHC) initiated the development of a Diabetes Care Management System
      (DCMS) in early 1998. The DCMS was developed as a comprehensive population-based
      disease management system. It includes provider education programs; performance
      feedback to physicians; clinical quality performance incentives for physicians;
      patient education programs; patient incentive, reminder systems to encourage
      compliance with best care process models; and tracking of physician behavior
      change and patient compliance with diabetes therapy. A multifaceted intervention
      and education approach was chosen because of the complexity of the diabetes
      treatment process. RESULTS: The percentage of patients with at least one annual
      HbA1c test increased from 78.5% in 1998 to 90.5% in 2002. During the same time
      period, the percentage of patients whose most recent HbA1c was less than 7.0
      increased from 33.5% to 52.8%, average HbA1c decreased from 8.1 to 7.3, and the
      percentage of patients whose most recent HbA1c was greater than 9.5 decreased
      from 34.6% to 21.4%. The percentage of patients who had an LDL cholesterol
      screening test within the prior 2 years increased from 65.9% in 1998 to 91.7% in
      2002. During the same time period, the percentage of patients whose most recent
      LDL cholesterol was less than 130 mg/dL increased from 39.9% to 69.8%. The
      percentage of diabetes patients who had an annual eye exam increased from 52% in
      1998 to 62% in 2002. CONCLUSION: A multifaceted approach to improving diabetes
      management has led to improved performance in clinical measures related to
      diabetes care that have been shown to reduce the risk of patients with diabetes
      developing diabetes- related complications. All components of the diabetes
      management continuum of care, including primary care physicians, specialists,
      office staff, patients, diabetes educators, and others, were involved in the care
      improvement activities.

PMID- 14664664
TI  - Examination of the evidence for off-label use of gabapentin.
AB  - OBJECTIVES: (1) Describe the relevance of off-label use of gabapentin to managed
      care pharmacy; (2) summarize recent FDA warnings and media reports related to off
      label gabapentin use; (3) review medical information pertaining to the off-label
      use of gabapentin; (4) outline alternatives to off-label use of gabapentin in an
      evidence-based fashion, where literature exists to support such alternatives; and
      (5) encourage key clinicians and decision makers in managed care pharmacy to
      develop and support programs that restrict the use of gabapentin to specific
      evidence-based situations. SUMMARY: Gabapentin is approved by the U.S. Food and
      Drug Administration (FDA) for adjunctive therapy in treatment of partial seizures
      and postherpetic neuralgia. Various off-label (unapproved) uses have been
      reported, and the use of gabapentin for off-label purposes has reportedly
      exceeded use for FDAapproved indications. Pharmaceutical marketing practices and
      physician dissatisfaction with currently available pharmacological treatment
      options may be key factors that contribute to this prescribing trend. Recently,
      the media has focused on these issues, noting that many cases of reported safety
      and effectiveness of gabapentin for off-label use may have been fabricated. A
      thorough review of the medical and pharmacy literature related to off-label use
      of gabapentin was performed, and a summary of the literature for the following
      conditions is presented: bipolar disorder, peripheral neuropathy, diabetic
      neuropathy, complex regional pain syndrome, attention deficit disorder, restless
      legs syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep,
      migraine headaches, and alcohol withdrawal syndrome. A common theme in the
      medical literature for gabapentin is the prevalence of open-label studies and a
      lack of randomized controlled clinical trials for all but a small number of
      indications. CONCLUSIONS: In the majority of circumstances where it has reported
      potential for.off-label. use, gabapentin is not the optimal treatment. The off
      label use of gabapentin for indications not approved by the FDA should be
      reserved for cases where there is solid research support (e.g., diabetic
      neuropathy and prophylaxis of frequent migraine headaches). Managed care
      pharmacists should develop programs to restrict the use of gabapentin to these
      specific evidence-based situations, and key decision makers in managed care
      practice should feel confident in supporting these use restrictions for
      gabapentin.

PMID- 14664665
TI  - Gabapentin may be appropriate for off-label uses.

PMID- 14664666
TI  - Use of drugs for off-label indications: living in the same world.

PMID- 14664667
TI  - Contractual arrangements between HMOs and medical groups to manage drug costs.

PMID- 14664668
TI  - Evidence-based medicine, practice guidelines, and disease management.

PMID- 14664669
TI  - The relative value of disease management programs versus drug manufacturer
      rebates.

PMID- 14664670
TI  - Disease management, pay-for-performance, and clinical pharmacist interventions in
      diabetes care.

PMID- 14664671
TI  - Consensus panel, national guidelines, and other potentially misleading terms.

PMID- 14664672
TI  - Transparency needed for economic analyses of PA programs.

PMID- 14664673
TI  - Transfer of route learning from virtual to real environments.
AB  - The authors investigated the extent to which route learning in a virtual
      environment (VE) transfers to the real world. In Experiment 1, active VE
      exploration, on its own or with a map, produced better transfer of training than
      either no VE training at all or passive VE training; however, transfer was
      achieved after shorter training times with the map. Experiment 2 demonstrated
      that VE + map training was not superior to training with a map alone, and
      Experiment 3 demonstrated that the poorer performances observed after passive VE
      training were not simply due to a lack of attention but to the lack of active
      navigational decisions. The authors concluded that the present VE technology does
      not provide better route learning than studying a map.

PMID- 14664674
TI  - Watching a cursor distorts haptically guided reproduction of mouse movement.
AB  - Participants moved a mouse along a force-feedback-defined linear path, either
      without vision or while watching a cursor set to 1 of 3 levels of visual:haptic
      gain (all >1:1). They attempted to haptically reproduce the movement without
      visual feedback. Errors increased with gain, reaching 70% overestimation at the
      highest gain. Forewarning participants about gain variability did not eliminate
      this effect. The gain level was potentially cued during the movement by the
      mismatch between visual feedback and kinesthetic feedback. Moreover, because
      participants did not achieve cursor-speed constancy across gain levels, visual
      speed was another cue to gain. Collectively, these cues failed to prevent visual
      distortion of movement reproduction.

PMID- 14664675
TI  - The adaptive user: an investigation into the cognitive and task constraints on
      the generation of new methods.
AB  - When people use a computer application, they have the opportunity to adapt the
      methods or strategies that they deploy to better fit the demands of the task. In
      Experiment 1, we demonstrated that the generation of methods is limited by, but
      not entirely prevented by, the reduced opportunity that is associated with the
      iterative nature of typical computer-based tasks. In Experiment 2, we
      demonstrated that the cognitive demands associated with task-related problem
      solving delay, but do not prevent, the generation of more efficient device
      strategies. We argue that people are rather good at adapting device strategies to
      task demands and that previously reported arguments to the contrary are
      premature.

PMID- 14664676
TI  - How to keep children safe in traffic: find the daredevils early.
AB  - Crossing the street in front of oncoming vehicles poses serious danger to young
      children. But is each young pedestrian similarly at risk? The authors aimed to
      identify children who are particularly prone to making risky and potentially
      harmful crossing decisions. They used a simple game involving risk to classify 5-
      to 6-year-olds as risk takers or risk avoiders. Children classified as risk
      takers made more crossing decisions at a busy 1-way street than risk avoiders,
      tolerated shorter time intervals between initiation of the crossing decision and
      arrival of the next vehicle, and were more likely to cause a (hypothetical)
      accident. Finally, they made decisions more quickly than risk avoiders. The
      authors discuss the implication of these results for traffic safety programs.

PMID- 14664677
TI  - Estimating the validity of the guilty knowledge test from simulated experiments:
      the external validity of mock crime studies.
AB  - This experiment was designed to examine the external validity of the standard
      mock-crime procedure used extensively to evaluate the validity of polygraph
      tests. The authors manipulated the type of mock-crime procedure (standard vs. a
      more realistic version) and the time of test (immediate vs. delayed) and examined
      their effects on the validity of the Guilty Knowledge Test (GKT) and the recall
      rate of the relevant items. The results indicated that only the type of mock
      crime affected the 2 outcome variables. The realistic procedure was associated
      with a lower recall rate and weaker detection efficiency than the standard
      procedure. However, these effects were mediated by the type of GKT questions
      used. Practical implications of these results are discussed.

PMID- 14664679
TI  - Meta-analysis of raw mean differences.
AB  - This article discusses the meta-analysis of raw mean differences. It presents a
      rationale for cumulating psychological effects in a raw metric and compares raw
      mean differences to standardized mean differences. Some limitations of
      standardization are noted, and statistical techniques for raw meta-analysis are
      described. These include a graphical device for decomposing effect sizes. Several
      illustrative data sets are analyzed.

PMID- 14664680
TI  - The metric comparability of meta-analytic effect-size estimators from factorial
      designs.
AB  - The primary studies in a meta-analysis of standardized mean differences generally
      include a mixture of single-factor t tests and multifactor analysis of variance
      designs. Accordingly, there is a need for effect-size measures in multifactor
      designs that are metrically comparable with measures in single-factor t tests.
      Two models, the variance-preservation model and the variance-reduction model,
      provide a formal description of the 2 principal routes by which a single-factor
      design may evolve into a higher order factorial design. New metrically comparable
      effect-size measures and estimators are developed for designs that contain
      variance-preservation factors, variance-reduction factors, or a mixture of both
      types of factors. A statistical test for checking the validity of model
      assumptions is presented.

PMID- 14664681
TI  - Generalized eta and omega squared statistics: measures of effect size for some
      common research designs.
AB  - The editorial policies of several prominent educational and psychological
      journals require that researchers report some measure of effect size along with
      tests for statistical significance. In analysis of variance contexts, this
      requirement might be met by using eta squared or omega squared statistics.
      Current procedures for computing these measures of effect often do not consider
      the effect that design features of the study have on the size of these
      statistics. Because research-design features can have a large effect on the
      estimated proportion of explained variance, the use of partial eta or omega
      squared can be misleading. The present article provides formulas for computing
      generalized eta and omega squared statistics, which provide estimates of effect
      size that are comparable across a variety of research designs.

PMID- 14664682
TI  - Effect-size indices for dichotomized outcomes in meta-analysis.
AB  - It is very common to find meta-analyses in which some of the studies compare 2
      groups on continuous dependent variables and others compare groups on
      dichotomized variables. Integrating all of them in a meta-analysis requires an
      effect-size index in the same metric that can be applied to both types of
      outcomes. In this article, the performance in terms of bias and sampling variance
      of 7 different effect-size indices for estimating the population standardized
      mean difference from a 2 x 2 table is examined by Monte Carlo simulation,
      assuming normal and nonnormal distributions. The results show good performance
      for 2 indices, one based on the probit transformation and the other based on the
      logistic distribution.

PMID- 14664683
TI  - Bidimensional regression: assessing the configural similarity and accuracy of
      cognitive maps and other two-dimensional data sets.
AB  - Bidimensional regression is a method for comparing the degree of resemblance
      between 2 planar configurations of points and, more generally, for assessing the
      nature of the geometry (Euclidean and non-Euclidean) between 2-dimensional
      independent and dependent variables. For example, it can assess the similarity
      between location estimates from different tasks or participant groups, measure
      the fidelity between cognitive maps and actual locations, and provide parameters
      for psychological process models. The authors detail the formal similarity
      between uni- and bidimensional regression, provide computational methods and a
      new index of spatial distortion, outline the advantages of bidimensional
      regression over other techniques, and provide guidelines for its use. The authors
      conclude by describing substantive areas in psychology for which the method would
      be appropriate and uniquely illuminating.

PMID- 14664684
TI  - r equivalent: A simple effect size indicator.
AB  - The purpose of this article is to propose a simple effect size estimate (obtained
      from the sample size, N, and a p value) that can be used (a) in meta-analytic
      research where only sample sizes and p values have been reported by the original
      investigator, (b) where no generally accepted effect size estimate exists, or (c)
      where directly computed effect size estimates are likely to be misleading. This
      effect size estimate is called r(equivalent) because it equals the sample point
      biserial correlation between the treatment indicator and an exactly normally
      distributed outcome in a two-treatment experiment with N/2 units in each group
      and the obtained p value. As part of placing r(equivalent) into a broader
      context, the authors also address limitations of r(equivalent).

PMID- 14664685
TI  - Power and measures of effect size in analysis of variance with fixed versus
      random nested factors.
AB  - Ignoring a nested factor can influence the validity of statistical decisions
      about treatment effectiveness. Previous discussions have centered on consequences
      of ignoring nested factors versus treating them as random factors on Type I
      errors and measures of effect size (B. E. Wampold & R. C. Serlin). The authors
      (a) discuss circumstances under which the treatment of nested provider effects as
      fixed as opposed to random is appropriate; (b) present 2 formulas for the correct
      estimation of effect sizes when nested factors are fixed; (c) present the results
      of Monte Carlo simulations of the consequences of treating providers as fixed
      versus random on effect size estimates, Type I error rates, and power; and (d)
      discuss implications of mistaken considerations of provider effects for the study
      of differential treatment effects in psychotherapy research.

PMID- 14664686
TI  - Therapists as fixed versus random effects-some statistical and conceptual issues:
      a comment on Siemer and Joormann (2003).
AB  - The authors disagree with M. Siemer and J. Joormann's assertion that therapist
      should be a fixed effect in psychotherapy treatment outcome studies. If treatment
      is properly standardized, therapist effects can be examined in preliminary tests
      and the therapist term deleted from analyses if such differences approach zero.
      If therapist effects are anticipated and either cannot be minimized through
      standardization or are specifically of interest because of the nature of the
      research question, the study has to be planned with adequate statistical power
      for including therapist as a random term. Simulation studies conducted by Siemer
      and Joormann confounded bias due to small sample size and inconsistent estimates.

PMID- 14664687
TI  - Should providers of treatment be regarded as a random factor? If it ain't broke,
      don't "fix" it: a comment on Siemer and Joormann (2003).
AB  - In their criticism of B. E. Wampold and R. C. Serlin's analysis of treatment
      effects in nested designs, M. Siemer and J. Joormann argued that providers of
      services should be considered a fixed factor because typically providers are
      neither randomly selected from a population of providers nor randomly assigned to
      treatments, and statistical power to detect treatment effects is greater in the
      fixed than in the mixed model. The authors of the present article argue that if
      providers are considered fixed, conclusions about the treatment must be
      conditioned on the specific providers in the study, and they show that in this
      case generalizing beyond these providers incurs inflated Type I error rates.

PMID- 14664688
TI  - Assumptions and consequences of treating providers in therapy studies as fixed
      versus random effects: reply to Crits-Christoph, Tu, and Gallop (2003) and
      Serlin, Wampold, and Levin (2003).
AB  - In their comments on the authors' article, R. C. Serlin, B. E. Wampold, and J. R.
      Levin and P. Crits-Christoph, X. Tu, and R. Gallop took issue with the authors'
      suggestion to evaluate therapy studies with nested providers with a fixed model
      approach. In this rejoinder, the authors' comment on Serlin et al's critique by
      showing that their arguments do not apply, are based on misconceptions about the
      purpose and nature of statistical inference, or are based on flawed reasoning.
      The authors also comment on Crits-Christoph et al's critique by showing that the
      proposed approach is very similar to, but less inclusive than, their own
      suggestion.

PMID- 14664689
TI  - Less guilty by reason of adolescence: developmental immaturity, diminished
      responsibility, and the juvenile death penalty.
AB  - The authors use a developmental perspective to examine questions about the
      criminal culpability of juveniles and the juvenile death penalty. Under
      principles of criminal law, culpability is mitigated when the actor's decision
      making capacity is diminished, when the criminal act was coerced, or when the act
      was out of character. The authors argue that juveniles should not be held to the
      same standards of criminal responsibility as adults, because adolescents'
      decision-making capacity is diminished, they are less able to resist coercive
      influence, and their character is still undergoing change. The uniqueness of
      immaturity as a mitigating condition argues for a commitment to a legal
      environment under which most youths are dealt with in a separate justice system
      and none are eligible for capital punishment.

PMID- 14664690
TI  - Toward a broader view of social stereotyping.
AB  - Stereotyping effects are typically considered to be assimilative in nature: A
      member of a group stereotyped as having some attribute is judged to have more of
      that attribute than a member of some comparison group. This article highlights
      the fact that stereotyping effects can also occur in the direction of contrast-
      or even null effects-- depending on the nature and form of the outcome being
      assessed (from the researcher's perspective, the dependent variable of interest).
      Relying on theory and research from the shifting standards model (M. Biernat, M.
      Manis, & T. F. Nelson, 1991), this review highlights the different ways in which
      and the factors that determine how stereotypes influence judgment and behavior
      toward individual group members.

PMID- 14664691
TI  - Psychology in the prescription era: building a firewall between marketing and
      science.
AB  - The pharmaceutical industry has contributed to many life-saving innovations in
      medicine and has become one of the most successful industries in the world. As a
      result, pharmaceutical industry financial and marketing influences extend to
      federal regulatory agencies, professional organizations, medical journals,
      continuing medical education, scientific researchers, media experts, and consumer
      advocacy organizations. These extensive influences have created conflicts of
      interest that have undermined the credibility of medical research and education.
      As professional psychology pursues and achieves prescription privileges, it will
      likely be faced with increasing influences from the industry. To preserve the
      integrity of psychological science, the authors propose an aspirational
      "firewall" designed to separate industry marketing from the science of
      psychology.

PMID- 14664694
TI  - Efficient selenium transfer from mother to offspring in selenoprotein-P-deficient
      mice enables dose-dependent rescue of phenotypes associated with selenium
      deficiency.
AB  - Mice deficient in selenoprotein P exhibit a disturbed selenium distribution and
      reduced activities of other selenoenzymes and display defects in growth and motor
      co-ordination. We have normalized selenoenzyme activities and rescued the
      phenotype of mutant mice by supplementing their nursing mothers with sodium
      selenite. Our results indicate that selenium from inorganic sources can be
      transferred efficiently via mother's milk to the developing offspring in a form
      that is both highly bioavailable by target tissues and yet sufficiently safe to
      prevent overdosages.

PMID- 14664695
TI  - The second metal-binding site of 70 kDa heat-shock protein is essential for ADP
      binding, ATP hydrolysis and ATP synthesis.
AB  - The chaperone activity of Hsp70 (70 kDa heat-shock protein) in protein folding
      and its conformational switch, including oligomeric and monomeric
      interconversion, are regulated by the hydrolysis of ATP and the ATP-ADP exchange
      cycle. The crystal structure of human ATPase domain shows two metal-binding
      sites, the first for ATP binding and a second, in close proximity to the first,
      whose function remains unknown [Sriram, Osipiuk, Freeman, Morimoto and Joachimiak
      (1997) Structure 5, 403-414]. In this study, we have characterized the second
      metal-binding motif by site-directed mutagenesis and the kinetics of ATP and ADP
      binding, and found that the second metal-binding site, comprising a loop co
      ordinated by His-227, Glu-231 and Asp-232, participates both in ATP hydrolysis
      and ATP-synthetic activities, in co-operation with the first metal-binding site.
      The first metal-binding site, a catalytic centre, is essential for ATP binding
      and the second site for ADP binding in the reactions of ATP hydrolysis and ATP
      synthesis.

PMID- 14664696
TI  - Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1:
      characterization of phosphorylation- and 14-3-3-dependent and -independent
      mechanisms.
AB  - FOXO1, a Forkhead transcription factor, is an important target of insulin and
      growth factor action. Phosphorylation of Thr-24, Ser-256 and Ser-319 promotes
      nuclear exclusion of FOXO1, yet the mechanisms regulating nuclear/cytoplasmic
      shuttling of FOXO1 are poorly understood. Previous studies have identified an NLS
      (nuclear localization signal) in the C-terminal basic region of the DBD (DNA
      binding domain), and a leucine-rich, leptomycin-B sensitive NES (nuclear export
      signal) located further downstream. Here, we find that other elements in the DBD
      also contribute to nuclear localization, and that multiple mechanisms contribute
      to nuclear exclusion of FOXO1. Phosphorylation of Ser-319 and a cluster of nearby
      residues (Ser-322, Ser-325 and Ser-329) functions co-operatively with the nearby
      NES to promote nuclear exclusion. The N-terminal region of FOXO1 (amino acids 1
      149) also is sufficient to promote nuclear exclusion, and does so through
      multiple mechanisms. Amino acids 1-50 are sufficient to promote nuclear exclusion
      of green fluorescent protein fusion proteins, and the phosphorylation of Thr-24
      is required for this effect. A leucine-rich, leptomycin B-sensitive export signal
      is also present nearby. Phosphorylated FOXO1 binds 14-3-3 proteins, and co
      precipitation studies with tagged proteins indicate that 14-3-3 binding involves
      co-operative interactions with both Thr-24 and Ser-256. Ser-256 is located in the
      C-terminal region of the DBD, where 14-3-3 proteins may interfere both with DNA
      binding and with nuclear-localization functions. Together, these studies
      demonstrate that multiple elements contribute to nuclear/cytoplasmic shuttling of
      FOXO1, and that phosphorylation and 14-3-3 binding regulate the cellular
      distribution and function of FOXO1 through multiple mechanisms. The presence of
      these redundant mechanisms supports the concept that the regulation of FOXO1
      function plays a critical role in insulin and growth factor action.

PMID- 14664697
TI  - Characterization of a cis-acting regulatory element in the protein-coding region
      of human dihydrofolate reductase mRNA.
AB  - Previous studies have shown that human DHFR (dihydrofolate reductase), in
      addition to its critical role in DNA biosynthesis, functions as an RNA-binding
      protein. The interaction between DHFR and its own mRNA results in translational
      repression. In this study, we characterized the cis-acting elements on human DHFR
      mRNA that are required for the DHFR mRNA-DHFR protein interaction. Using a series
      of gel-shift and nitrocellulose filter-binding assays, a 164 nt RNA sequence,
      corresponding to nt 401-564, was identified within the coding region that binds
      to DHFR protein with an affinity similar to that of full-length DHFR mRNA. To
      document in vivo biological activity, various DHFR sequences contained within the
      coding region were cloned on to the 5' end of a luciferase reporter plasmid, and
      transient transfection experiments were performed using human colon cancer RKO
      cells. In cells transfected with p644/DHFR:401-564, luciferase activity was
      decreased by 50% when compared with cells transfected with the p644 plasmid
      alone. Luciferase mRNA levels were identical under each of these conditions, as
      determined by Northern-blot analysis. In cells transfected with p644/DHFR:401
      564, luciferase activity was restored to almost 100% of control when cells were
      treated with the antifolate analogue methotrexate or with a short-interfering RNA
      targeting DHFR mRNA. These findings provide evidence that the DHFR 401-564
      sequence is a DHFR-response element. In vitro and in vivo studies further
      localized this cis-element to an 82 nt sequence corresponding to nt 401-482. This
      work provides new insights into critical elements that mediate RNA-protein
      interactions.

PMID- 14664698
TI  - Has the mechanism by which the endocrine placenta scavenges the mother whilst
      sparing the foetus been unmasked?
AB  - The endocrine placenta has a dilemma; it shares the foetal circulation and yet it
      needs to secrete active peptide hormones into the maternal circulation to control
      her metabolism to meet the demands of the growing foetus. Simultaneously, it
      needs to allow the endocrine systems of the foetus to develop independently. This
      Article will describe how peptide hormones are processed from inactive
      intermediates and will propose a hypothesis of how the placenta has revised this
      process to protect the foetus from the potentially damaging affects of these
      products.

PMID- 14664699
TI  - Estrogen receptor-related receptors: orphan receptors desperately seeking a
      ligand.
AB  - The nuclear receptor family comprises ligand-dependent and orphan receptors. To
      the latter group belong the estrogen receptor-related receptors (ERRs) for which
      conflicting results have been published concerning the nature (constitutive or
      liganded) of their transcriptional activities. ERRs interfere in various ways,
      positively and negatively, with estrogen signaling. Moreover recent data
      analyzing ERR expression in human breast tumors have proposed ERRalpha and
      ERRgamma as prognostic markers of these cancers. The identification of modulators
      (positive or negative) of ERR activities would therefore be highly useful in our
      understanding of estrogen-related pathologies. The purpose of this review is to
      summarize our knowledge of the nature of ERR activities and progresses in
      identifying synthetic ERR modulators.

PMID- 14664700
TI  - The angiotensin type 2 receptor of angiotensin II and neuronal differentiation:
      from observations to mechanisms.
AB  - The angiotensin II (Ang II) type 2 receptor (AT(2)) is a member of the seven
      transmembrane domain, G-protein coupled receptor family. This receptor is
      ubiquitously distributed in the fetus but, in most tIssues, its expression
      dramatically falls in the first few hours after birth. Based on this observation,
      the hypothesis that this receptor could be involved in fetal development was
      raised and, over the past ten Years, many studies have tried to identify a role
      for the AT(2) receptor using many different tIssues and cell lines. To date, one
      of the major roles associated with the Ang II AT(2) receptor concerns its ability
      to induce neuronal differentiation. Indeed, in cells of neuronal origin,
      activation of the AT(2) receptor was shown to induce neurite outgrowth and
      elongation, modulate neuronal excitability, promote cellular migration and, in
      particular conditions, induce neuronal cell death. Regarding its signaling
      mechanisms, the AT(2) receptor still represents one of the most controversial G
      protein coupled receptors since it does not stimulate the production of any of
      the classical second messengers. This review summarizes knowledge of the
      functions and the signaling mechanisms involved in the actions of the AT(2)
      receptor in neurons and cells of neuronal origin. Based on its altered expression
      in neurological disorders, a role for the AT(2) receptor in control of neuronal
      plasticity is proposed.

PMID- 14664701
TI  - Central role of defective apoptosis in autoimmunity.
AB  - Lymphocyte development, selection and education represent tightly controlled
      immune processes that normally prevent autoimmunity. Lymphocyte development
      likely induces cellular selection through apoptosis to remove potentially
      autoreactive cells. Dysregulated apoptosis, both interrupted as well as
      accelerated apoptosis, are now demonstrated as central defects in diverse murine
      autoimmune disease. In murine models of autoimmune lupus, mutations in cell death
      receptor Fas (CD95) and its ligand, FasL (CD95 L), have been identified. These
      errors create a lymphoid system resistant to apoptosis. In contrast, select
      lymphoid subpopulations of maturing autoimmune prone non-obese diabetic mice have
      identifiable and pathogenic T cells with both in vivo and in vitro heightened
      apoptosis after drug interventions. In part, these defects are due to faulty
      activation of transcription factors such as nuclear factor-kappaB (NF-kappaB)
      that normally protect against apoptotic death. The genetic basis of interrupted
      NF-kappaB in pathogenic memory T cells in diabetes is attributable to a
      developmentally controlled gene defect in an essential subunit of the proteasome.
      No specific gene in most common forms of human autoimmune disease has yet been
      identified. Functional assays from diverse laboratories repeatedly demonstrate
      heightened apoptosis in multiple cellular signaling pathways for cell death,
      suggesting a common theme in disease causality.

PMID- 14664702
TI  - Diminished penile expression of vascular endothelial growth factor and its
      receptors at the insulin-resistant stage of a type II diabetic rat model: a
      possible cause for erectile dysfunction in diabetes.
AB  - Erectile dysfunction (ED) is commonly experienced in men with diabetes mellitus.
      Vascular endothelial growth factor (VEGF) has been extensively documented for its
      pathogenic significance in different complications of diabetes. We hypothesized
      that expressions of VEGF, its receptors and its signaling pathway Akt may be
      drastically altered in diabetic penile tIssues and their alterations may modulate
      penile expression of the molecules that are believed to play a role in diabetic
      ED. Otsuka Long-Evans Fatty (OLETF) rats, a type II (non-insulin-dependent)
      diabetes mellitus, were used at the insulin-resistant stage of type II diabetes
      (20 weeks of age). We determined protein and mRNA expressions of VEGF, its
      receptors, Akt, nitric oxide synthase isoforms, and apoptosis-related molecules
      in the penis using immunohistochemistry, Western blotting, in situ hybridization,
      and real-time quantitative PCR analyses. The penile sections were also submitted
      to the Tdt-mediated dUTP nick end labeling assay for apoptosis. OLETF rats showed
      marked reductions in penile expression of VEGF, its two receptors and Akt. In
      OLETF rat penises, endothelial and neuronal nitric oxide synthase isoforms were
      expressed less abundantly. Furthermore, while anti-apoptotic markers, Bcl-2 and
      phosphorylated Bad, were down-regulated, pro-apoptotic markers, active caspase-3
      and Bax, were up-regulated, resulting in the appearance of apoptotic cells in the
      penile tIssues of OLETF rats. The VEGF signaling system would work less well in
      diabetic penile tIssues as a result of the reduced expression, leading to
      diminished endothelial production of nitric oxide and apoptosis-related erectile
      tIssue damage. We propose that the abnormalities of the VEGF signaling system in
      the penis may play a role in the pathophysiology of diabetic ED.

PMID- 14664703
TI  - Isolation and characterization of an alternatively spliced variant of
      transcription factor Islet-1.
AB  - The LIM homeodomain protein Islet-1 (Isl1), one of the earliest markers for motor
      neuron differentiation, is also expressed in all classes of islet cells in the
      pancreas. Isl1 is known to bind and regulate the promoters of the insulin,
      glucagon and somatostatin genes. In this study, we describe isolation of a novel
      isl1 cDNA species from the mouse islet beta cell line betaTC6, which arose from
      the utilization of an alternative splicing acceptor site in the fifth exon. This
      shorter cDNA encodes an Isl1 isoform (Isl1-beta) lacking the carboxy-terminal 23
      amino acids of the previously reported product Isl1-alpha. Although the level of
      isl1-beta mRNA is much lower than that of isl1-alpha, isl1-beta is preferentially
      expressed in murine insulinoma cell lines but not in glucagonoma cell line. Upon
      transient transfection, both Isl1-alpha and Isl1-beta accumulate in the nuclei of
      murine insulinoma cells. We found that Isl1-beta is a relatively more potent
      transcriptional activator of the insulin promoter than Isl1-alpha and that the
      Isl1-alpha isoform undergoes phosphorylation. Therefore, the transcriptional
      activity of Isl1 is potentially regulated by the alternative splicing of its mRNA
      and by phosphorylation.

PMID- 14664704
TI  - Role of conserved hydrophobic amino acids in androgen receptor AF-1 function.
AB  - The intracellular androgen receptor (AR) is a ligand-activated transcription
      factor. Upon binding the steroids testosterone or dihydrotestosterone, the
      activated receptor translocates to the nucleus, binds to specific DNA response
      elements and interacts with the transcription machinery in order to regulate gene
      transcription. In the present study, we have described a highly conserved region
      (amino acids 224-258) within the AR AF-1 domain and have investigated the role of
      conserved bulky hydrophobic residues in gene regulation. Mutating pairs of
      residues (I229A/L236A; V240A/V242A; L251A/L254A) reduced transactivation activity
      by 25-40%. Mutating residues M244, L246 and V248 to alanines had a more dramatic
      affect on receptor activity, disrupting activity by at least 60%. The latter
      mutations also disrupted binding to the RNA polymerase-associated protein 74
      subunit of the general transcription factor TFIIF. The protein conformation and
      stability of the mutant polypeptide in vitro was not significantly different from
      the wild type. None of the mutations tested disrupted binding of the AF-1 domain
      with the coactivator protein steroid receptor coactivator-1a. Thus we have
      concluded that conserved hydrophobic residues are important for receptor
      dependent gene transcription and that M244, L246 and V248 are part of the binding
      interface for TFIIF.

PMID- 14664706
TI  - Threshold effects of glucose transporter-4 (GLUT4) deficiency on cardiac glucose
      uptake and development of hypertrophy.
AB  - The aim of this study was to investigate the metabolic and structural
      consequences of a decrease in glucose transporter-4 (GLUT4) levels on the heart.
      The CreLoxP system was utilised to delete GLUT4 in muscle tIssue including heart.
      The presence of the PGK-neoR cassette in the GLUT4-Lox mice resulted in reduced
      expression in all tIssues to levels 15-30% of wild-type control mice. In mice
      expressing Cre recombinase, there was a further reduction of GLUT4 in cardiac
      tIssue to almost undetectable levels. Cardiac glucose uptake was measured basally
      and during a euglycaemic/hyperinsulinaemic clamp using 2-deoxy-[1-(14)C]glucose.
      Insulin-stimulated glucose uptake was normal in hearts expressing 15% of normal
      GLUT4 levels but markedly reduced in mice with more profound reduction in GLUT4.
      Cardiac enlargement occurred only when GLUT4 levels were less than 5% of normal
      values. In heart there is a threshold level of GLUT4 above which insulin
      stimulated glucose uptake is maintained. As little as 5% of normal GLUT4 levels
      expressed in heart is sufficient to prevent the development of cardiac
      hypertrophy.

PMID- 14664705
TI  - The effects of GH-releasing hormone/somatostatin on the 5'-promoter activity of
      the GH gene in vitro.
AB  - The two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin
      (SRIF), are known to regulate GH secretion. However, the effects of these
      hormones on GH gene expression are not completely clear, partly because of the
      lack of appropriate host cells maintaining the original characteristics of the
      somatotroph. Since MtT/S, a pure somatotroph cell line, has become available, the
      effects of GHRH and SRIF on GH gene transcription have been studied using a
      subclone of MtT/S (MtT/SGL), in which the GH gene 5'-promoter-luciferase fusion
      gene was stably incorporated. The expression of GHRH receptor and SRIF receptor
      subtypes was also studied by RT-PCR. The results showed that MtT/SGL cells
      intrinsically expressed the functional GHRH receptor and all of the SRIF receptor
      subtypes. The expression of GHRH receptor was markedly enhanced by glucocorticoid
      pretreatment and, in the presence of corticosterone and 3-isobutyl-1
      methylxanthine, GHRH (at or above 100 pM) stimulated GH gene 5'-promoter activity
      in a dose-dependent manner. On the other hand, SRIF (100 nM) significantly
      antagonized the effect of GHRH, which was completely reversed by pretreatment
      with pertussis toxin (50 ng/ml). Taken together, the present data indicated that
      both GHRH and SRIF are involved in the transcriptional regulation of the GH gene,
      and that the effect of SRIF is mediated through pertussis toxin-sensitive G
      protein. The MtT/SGL cell line is a good in vitro model for studying the
      molecular mechanisms of GH gene transcription by GHRH and/or SRIF.

PMID- 14664707
TI  - Identification of dimeric and oligomeric complexes of the human oxytocin receptor
      by co-immunoprecipitation and bioluminescence resonance energy transfer.
AB  - The nonapeptide hormone oxytocin exerts many important biological functions,
      including uterine contractions during parturition and milk ejection during
      lactation. The manifold effects of oxytocin are mediated by a single oxytocin
      receptor (OTR) type, a member of the super-family of G-protein-coupled receptors.
      There is accumulating recent evidence that certain G-protein-coupled receptors
      exist in the form of oligomeric complexes. Here we demonstrate, using two
      different co-immunoprecipitation strategies as well as bioluminescence resonance
      energy transfer techniques, that the OTR is capable of forming oligomeric
      complexes in vivo and that these complexes exist at the cell surface membrane.
      The human OTR was N-terminally tagged with either a Myc or Flag epitope and
      transiently expressed in COS-7 cells. Cell lysates were immunoprecipitated using
      an anti-Flag antibody and analyzed by SDS-PAGE and Western blotting using an anti
      Myc antibody, or vice versa. Either strategy provided evidence for the co
      precipitation of Myc- or Flag-tagged OTR respectively. Biochemical
      characterization of OTR dimers showed that homodimer formation is not dependent
      on the establishment of disulfide bonds. The existence of OTR dimers and
      oligomers at the level of the cell surface was demonstrated by exposing intact
      living cells to an anti-Flag antibody and analyzing the immunoprecipitate by
      Western blotting with an anti-Myc antibody. This approach demonstrated
      furthermore that the presence of receptor oligomers at the cell surface is
      modulated by ligand in a time-dependent fashion. Finally, we obtained evidence
      that the OTR is forming oligomeric structures in intact living cells by observing
      the occurrence of bioluminescence resonance energy transfer in cells co
      transfected with OTR constructs bearing at their C-terminus either a Renilla
      luciferase or the yellow fluorescent protein. Taken together, these data show
      that the OTR can form homodimers and oligomers in the cell model used and that
      these oligomers are present at the cell surface.

PMID- 14664708
TI  - Regulation of transcripts encoding ADAMTS-1 (a disintegrin and metalloproteinase
      with thrombospondin-like motifs-1) and progesterone receptor by human chorionic
      gonadotropin in equine preovulatory follicles.
AB  - One member of a new family of metalloproteinases, a disintegrin and
      metalloproteinase with thrombospondin-like motifs-1 (ADAMTS-1), has been found to
      be expressed and hormonally induced in granulosa cells of ovulating rodent
      follicles. Furthermore, the targeted disruption of the ADAMTS-1 gene resulted in
      ovarian defects associated with severely impaired fertility. While these data
      demonstrate the importance of ADAMTS-1 in rodent ovarian physiology, the
      potential role of ADAMTS-1 in the ovulatory process of monoovulatory species
      remains unknown. The objectives of this study were to clone the equine ADAMTS-1
      primary transcript and to study its regulation during human chorionic
      gonadotropin (hCG)-induced ovulation. A 3573 bp follicular cDNA library clone was
      isolated and found to encode a nearly complete, highly conserved ADAMTS-1
      homologue. Real-time RT-PCR analysis detected this transcript in diverse tIssues,
      including previously unreported sites of ADAMTS-1 expression such as the male
      reproductive tract, the follicular theca interna and the mature corpus luteum.
      The tIssue distribution of the progesterone receptor (PR), a known regulator of
      ADAMTS-1 expression in rodent preovulatory follicles, was found to overlap that
      of ADAMTS-1 in some tIssues. A study of the regulation of follicular ADAMTS-1 and
      PR mRNAs during the hCG-induced ovulatory process revealed distinct patterns of
      regulation in granulosa cells and in theca interna. In granulosa cells, ADAMTS-1
      mRNA was found to be induced at 12 h post-hCG (P<0.05), followed by a return to
      basal levels by 30 h and a re-increase at 33-39 h (P<0.05). A concomitant
      increase in PR mRNA (P<0.05) was observed at 12 h post-hCG. In theca interna,
      abundant ADAMTS-1 mRNA was detected at all timepoints, and levels increased
      transiently at 33 h post-hCG (P<0.05), whereas no significant change was observed
      in PR mRNA. Together, these data demonstrate for the first time the hormonally
      regulated ovarian expression of ADAMTS-1 in a monoovulatory species, and identify
      a novel biphasic regulation of ADAMTS-1 in granulosa cells and a regulated
      expression in theca interna that were not previously observed in rodents.

PMID- 14664709
TI  - Similarities and differences in uterine gene expression patterns caused by
      treatment with physiological and non-physiological estrogens.
AB  - Administration of physiological and non-physiological estrogens during pregnancy
      or after birth is known to have adverse effects on the development of the
      reproductive tract and other organs. Although it is believed that both estrogens
      have similar effects on gene expression, this view has not been tested
      systematically. To compare the effects of physiological (estradiol; E2) and non
      physiological (diethylstilbestrol; DES) estrogens, we used DNA microarray
      analysis to examine the uterine gene expression patterns induced by the two
      estrogens. Although E2 and DES induced many genes to respond in the same way,
      different groups of genes showed varying levels of maximal activities to each
      estrogen, resulting in different dose-response patterns. Thus, each estrogen has
      a distinct effect on uterine gene expression. The genes were classified into
      clusters according to their dose-responses to the two estrogens. Of the eight
      clusters, only two correlated well with the uterotropic effect of different doses
      of E2. One of these clusters contained genes that were upregulated by E2, which
      included genes encoding several stress proteins and transcription factors. The
      other cluster contained genes that were downregulated by E2, including genes
      related to metabolism, transcription and detoxification processes. The expression
      of these genes in estrogen receptor-deficient mice was not affected by E2
      treatment, indicating that these genes are affected by the E2-bound estrogen
      receptor. Thus, of the many genes that are affected by estrogen, it was suggested
      that only a small number are directly involved in the uterotropic effects of
      estrogen treatment.

PMID- 14664710
TI  - cDNA cloning of chicken orexin receptor and tissue distribution: sexually
      dimorphic expression in chicken gonads.
AB  - Orexin-A and -B are known to stimulate food intake in mammals. However, the
      critical roles of orexins in birds are not fully understood, since orexins have
      no stimulatory effect on food intake in the chicken. To understand the
      physiological role(s) of orexins in birds, we have cloned chicken orexin receptor
      (cOXR) cDNA by RT-PCR, and analysed the tIssue distribution of OXR mRNA in the
      chicken. The cOXR cDNA is 1869 bp long and encodes 501 amino acids. The cloned
      cDNA for cOXR corresponds to the type 2 OXR in mammals, and shows approximately
      80% similarity to those of mammals at the amino acid level. Expression analysis
      by RNase protection assay revealed OXR mRNA was distributed widely in brain
      regions, and expression in the cerebrum, hypothalamus and optic tectum were
      abundant. In peripheral tIssues, OXR mRNA was expressed in the pituitary gland,
      adrenal gland and testis, but no mRNA expression was observed in other tIssues
      examined. Furthermore, we found that the amount of cOXR mRNA was different
      between testis and ovary, while prepro-orexin mRNA is equally expressed in the
      gonads of both sexes in the chicken. These data indicate that the orexins have
      neuroendocrine actions in chickens, which are mediated through hypothalamic
      receptors as has been observed in mammals. In addition, orexin may have specific
      role(s) in the regulation of gonadal function in which sex-dependent mechanisms
      could be involved.

PMID- 14664711
TI  - Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its
      protein or mRNA expression in insulin-producing cells.
AB  - Pancreatic beta-cells have low activities of the antioxidant enzyme catalase.
      Nitric oxide interacts with the haem group of catalase inhibiting its activity.
      We have studied the activity of catalase in beta-cells under conditions mimicking
      prediabetes and in which nitric oxide is generated from cytokine treatment in
      vitro. We also studied whether there is regulation of catalase enzyme activity by
      nitric oxide at the protein or gene expression level. RINm5F insulin-producing
      cells, treated for 24 h with cytokines, showed increased medium nitrite
      production (17+/-2.2 vs 0.3+/-0.2 pmol/ micro g protein) and significantly
      decreased cellular catalase activity (42.4+/-4.5%) compared with control cells. A
      similar reduction was seen in catalase-overexpressing RIN-CAT cells and in rat or
      human pancreatic islets of Langerhans. Catalase activity was also suppressed by
      the long-acting nitric oxide donor diethylenetriamine/nitric oxide adduct (Deta
      NO) and this inhibition was reversible. The inhibition of catalase activity by
      cytokines in RINm5F cells was significantly reversed by the addition of the
      nitric oxide synthase 2 (NOS2) inhibitors nitro monomethylarginine or N-(3
      (aminomethyl)benzyl)acetamidine (1400W). Protein expression was found to be
      unchanged in cytokine- or Deta-NO-treated RINm5F cells, while mRNA expression was
      marginally increased. We have shown that inhibition of catalase activity by
      cytokines is nitric oxide dependent and propose that this inhibition may confer
      increased susceptibility to cytokine- or nitric oxide-induced cell killing.

PMID- 14664712
TI  - Expression profile of mRNAs from human pancreatic islet tumors.
AB  - In order to understand the tIssue specificity of the endocrine pancreas, it is
      important to clarify the expression profile of mRNAs in various states of the
      tIssue. A total of approximately 9000 non-redundant expressed genes from human
      pancreatic islets and insulinoma have so far been determined as expressed
      sequence tags (ESTs) and deposited in public databases. In the present study
      towards the identification of a complete set of genes expressed in human
      pancreatic islets, we have determined 3'-ESTs of 21267 clones randomly selected
      from a cDNA library of human pancreatic islet tumors. Clustering analysis
      generated 6157 non-redundant sequences comprising 2323 groups and 3834
      singletons. Nucleotide and peptide database searches show that 3103 of them
      represent known human sequences or homologs of genes identified in other species
      and 58 are new members of structurally related families. The sequences were
      classified on the basis of the putative protein functions encoded, and were
      assigned to the respective chromosome by database analysis. The sequences were
      also compared with the EST databases (dbEST and EPConDB) including ESTs from
      normal pancreatic islet, insulinoma, and fetal pancreas. Since 3384 genes were
      newly found to be expressed in human pancreatic islets and 587 of them were
      unique to the islets, this study has considerably expanded the catalog of genes
      expressed in the endocrine pancreas. The larger collection of pancreatic islet
      related ESTs should provide a better genome source for molecular studies of
      differentiation, tIssue-specific functions, and tumorigenesis of the endocrine
      pancreas as well as for genetic studies of diabetes mellitus.

PMID- 14664713
TI  - Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7
      36)amide have preserved biological activities in vitro conferring improved
      glucose-lowering action in vivo.
AB  - Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent
      stimulator of insulin release, its rapid degradation in vivo by the enzyme
      dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of
      type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1,
      (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation
      by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate
      affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor
      compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1
      dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with
      reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively).
      Consistent with other mechanisms of action, the analogues showed similar, or in
      the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN
      BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose
      lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced
      by 37%. The in vivo insulin-releasing activities were similar. These data
      indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance
      to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N
      terminally modified GLP-1 analogue of possible use in type 2 diabetes.

PMID- 14664714
TI  - Hypothyroidism induces type 2 iodothyronine deiodinase expression in mouse heart
      and testis.
AB  - In the present study we show the expression profiles of both type 1 and type 2
      iodothyronine deiodinases (D1 and D2) in a wide spectrum of mouse tIssues, and D2
      regulation by thyroid status. A characteristic tIssue-specific expression for
      each isoform was observed. D2 transcripts were detected in most tIssues with
      variable levels of expression. The observed D2 mRNA tIssue distribution was
      similar to that described in rats and is in agreement with the view of different
      patterns of expression between rodents and humans. However, it is interesting to
      note that despite the low levels of D2 transcripts in mouse heart and testis in
      the euthyroid state, the induction of hypothyroidism caused a significant
      increase in D2 activity in these tIssues. Similar results were also obtained in
      adult rats. These results suggest a previously unrecognized role for type 2
      deiodinase in controlling intracellular triiodothyronine levels in rodent heart
      and testis during states of thyroid hormone deficiency.

PMID- 14664715
TI  - The different effects of endocrine-disrupting chemicals on estrogen receptor
      mediated transcription through interaction with coactivator TRAP220 in uterine
      tissue.
AB  - An endocrine-disrupting chemical (EDC) can alter endocrine functions through a
      variety of mechanisms, including nuclear receptor-mediated changes in protein
      synthesis, interference with membrane receptor binding, steroidogenesis or
      synthesis of other hormones. Although major chemicals have been shown to disrupt
      estrogenic actions mainly through their binding to estrogen receptor (ER) or
      androgen receptor, it is not clear how EDCs affect endocrine functions in vivo.
      We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated
      transcription through interaction with TRAP220. Moreover, bisphenol A had
      positive effects on the interaction between ER-beta and TRAP220 and on the
      expression of ER-beta and TRAP220 compared with phthalate and estradiol in
      uterine tIssue. These data suggested that some EDCs might alter endocrine
      function through the change of the receptor and coactivator levels in uterine
      tIssue and through the different effect on the interaction between ERs and
      coactivator TRAP220.

PMID- 14664716
TI  - The recovery of some components of the renin angiotensin system in the rat
      pancreas after chronic exposure to hypoxic condition.
AB  - Previous studies have shown that the expression of the major components from a
      local pancreatic renin-angiotensin system (RAS) was upregulated after chronic
      exposure to oxygen deprivation (10% oxygen). In the present study, the
      reversibility of expression for the pancreatic RAS affected by chronic hypoxia
      was investigated in the pancreas. Rats were first subject to hypoxia for one
      Month and they were then returned to normoxic conditions for a varying period of
      time (1, 2, 3 and 4 weeks). The degree of recovery in the expression of RAS
      components was analyzed with standard curve-quantitative competitive-reverse
      transcription-polymerase chain reaction (SC-QC-RT-PCR), Western blot analysis and
      a specific assay for angiotensin-converting enzyme (ACE) activity. Results from
      SC-QC-RT-PCR showed that the upregulated expression of angiotensin II type 1
      (AT(1)) receptor mRNA following chronic hypoxia could be completely restored to
      the control level after the rats were returned to the normoxic condition for 3
      weeks. The reversibility of mRNA expression for angiotensin II type 2 (AT(2))
      receptor and angiotensinogen was observed after the return to normoxic conditions
      for 2 and 3 weeks respectively when compared with that of their respective
      controls. Results from Western blot analysis further confirmed that the
      expression of AT(1) receptor protein was also reversible after return to normoxic
      conditions for 4 weeks. In addition, the activation of ACE activity returned to
      its normal level in a time-dependent manner. These data indicate that the
      upregulation of a local pancreatic RAS affected by chronic hypoxia could be
      recoverable. The significance of its reversibility and adaptability following
      chronic hypoxia may be of physiological relevance to the pancreas.

PMID- 14664717
TI  - Determinants of spironolactone binding specificity in the mineralocorticoid
      receptor.
AB  - Spironolactone is a mineralocorticoid receptor (MR) antagonist in clinical use.
      The compound has a very low affinity for the glucocorticoid receptor (GR).
      Determinants of binding specificity of spironolactone to the MR were investigated
      using chimeras created between the ligand-binding domains (LBDs) of the MR and
      the GR. These chimeras had previously been used to investigate aldosterone
      binding specificity to the MR. Spironolactone was able to compete strongly for
      [(3)H]-aldosterone and [(3)H]-dexamethasone binding to a chimera containing amino
      acids 804-874 of the MR, and weakly for [(3)H]-dexamethasone binding to a chimera
      containing amino acids 672-803 of the MR. Amino acids 804-874 were also critical
      for aldosterone binding specificity. Models of the MR LBD bound to aldosterone
      and spironolactone were created based on the crystal structure of the
      progesterone receptor LBD. The ligand-binding pocket of the MR LBD model
      consisted of 23 amino acids and was predominantly hydrophobic in nature. Analysis
      of this model in light of the experimental data suggested that spironolactone
      binding specificity is not governed by amino acids in the ligand-binding pocket.

PMID- 14664718
TI  - The retinoblastoma protein-associated transcription repressor RBaK interacts with
      the androgen receptor and enhances its transcriptional activity.
AB  - In search of potential androgen receptor coregulators we performed a yeast two
      hybrid screening using the androgen receptor ligand-binding domain as bait and a
      human prostate cDNA library as prey and found that the carboxy-terminal domain of
      retinoblastoma-associated Kruppel protein (RbaK), a member of the Kruppel zinc
      finger protein family, interacts in a ligand-dependent way with the ligand
      binding domain of the androgen receptor. RBaK was recently identified as a
      transcriptional regulator that interacts with the retinoblastoma protein and
      thereby influences E2F regulated transcription. The interaction of RBaK with the
      androgen receptor was further documented using mammalian two-hybrid experiments,
      in vitro binding studies and coimmunoprecipitation. Finally, we demonstrated that
      both RBaK and the retinoblastoma protein coactivate androgen receptor-mediated
      transcription in cotransfection experiments. In conclusion, our data show that
      RBaK interacts with the androgen receptor and increases its transcriptional
      activity. Moreover, the double interaction of RBaK with the retinoblastoma
      protein and with the androgen receptor provides a novel link between the androgen
      receptor and the regulation of the cell cycle.

PMID- 14664719
TI  - Enhanced expression of a furin-cleavable proinsulin.
AB  - Cell engineering or gene therapy may represent an alternative to current methods
      of treating diabetes mellitus. Cells could be engineered to secrete insulin ex
      vivo for transplantation or the insulin gene could be administered directly by
      injection into muscle. A problem has been that non-neuroendocrine cells lack the
      endoproteases (PC3/1 and PC2) that are responsible for the processing of
      proinsulin to insulin. This can be surmounted by engineering the paired basic
      amino acid processing sites within proinsulin to sites that would be recognized
      by the ubiquitously expressed protease, furin. However, in every study to date,
      the expression of the furin-cleavable construct was greatly reduced relative to
      that of the unmodified proinsulin construct. We investigated possible causes for
      this, including mRNA stability, the presence of additional CpG islands, and the
      amino acid substitutions within furin-cleavable proinsulin. Several furin
      cleavable rat proinsulin I cDNAs were engineered and used to transfect human
      HEK293, rat L6 and mouse C(2)C(12) cell lines. The stability of wild-type and
      furin-cleavable proinsulin mRNA in transfected C(2)C(12) cells was measured by RT
      PCR. Comparison of the decay rates in the presence of actinomycin D showed no
      significant difference between the two species of mRNA. A furin-cleavable
      proinsulin cDNA was created to contain the same distribution of CpG islands as
      wild-type proinsulin. Comparison of insulin-like immunoreactivity in all three
      cell lines transfected with either this construct or a widely used furin
      cleavable proinsulin containing additional CpG islands showed that the presence
      of the extra CpG islands had no effect. Studies to examine amino acid
      substitutions used to create furin consensus sequences showed that the addition
      of basic residues at the C-peptide/A-chain junction was responsible for the
      reduced production of furin-cleavable proinsulin. Using this information, we
      engineered a cDNA for furin-cleavable rat proinsulin I that was efficiently
      processed to mature insulin and expressed at the same level as wild-type
      proinsulin.

PMID- 14664720
TI  - Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA
      expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6,
      and tumor necrosis factor-alpha on equine parathyroid cell function.
AB  - Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland
      in response to changes in ionized calcium (Ca(2+)) concentrations. In this study,
      we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA
      expression by equine parathyroid chief cells in vitro. We also evaluated the
      effects of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha on
      PTH secretion, and PTH and CaR mRNA expression. The relationship between PTH and
      Ca(2+) was inversely related. PTH secretion decreased from 100% (day 0) to 13%
      (day 30). PTH mRNA expression declined from 100% (day 0) to 25% (day 30). CaR
      mRNA decreased from 100% (day 0) to 16% (day 30). Chief cells exposed to high
      (2.0 mM) Ca(2+) concentrations had a lower PTH mRNA expression compared with low
      Ca(2+) concentrations. Ca(2+) concentrations had no effect on CaR mRNA
      expression. The inhibitory effect of high Ca(2+) concentrations on PTH secretion
      also declined over time. After day 10, there was no significant difference in PTH
      secretion between low and high Ca(2+ )concentrations. IL-1beta decreased both PTH
      secretion (75%) and PTH mRNA expression (73%), and resulted in a significant
      overexpression of CaR mRNA (up to 142%). The effects of IL-1beta were blocked by
      an IL-1 receptor antagonist. IL-1beta decreased the Ca(2+) set-point from 1.4 mM
      to 1.2 mM. IL-6 decreased PTH secretion (74%), but had no effect on PTH and CaR
      mRNA expression. TNF-alpha had no effect on PTH secretion, and PTH and CaR mRNA
      expression. In summary, the decreased responsiveness of parathyroid cells to
      Ca(2+) from 0 to 30 days can be explained, in part, by the reduced CaR
      expression. IL-1beta and IL-6 but not TNF-alpha affected parathyroid function in
      vitro and may be important in influencing PTH secretion in the septic horse.

PMID- 14664721
TI  - A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma.
AB  - ABSTRACT : BACKGROUND : Mantle cell lymphoma (MCL) is a rare variety of non
      Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle
      zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph
      nodes with invasive breast cancers without prior history of adjuvant chemotherapy
      or radiotherapy has not been previously reported in literature. CASE REPORT : We
      report a rare case of breast cancer co-existing with stage I mantle cell lymphoma
      of the ipsilateral axillary lymph node detected fortuitously by population
      screening. CONCLUSION : Though some studies have tried to prove breast carcinomas
      and lymphomas to share a common molecular or viral link, more research needs to
      be done to establish whether such a link truly exists.

PMID- 14664722
TI  - DNA fingerprinting of Shiga-toxin producing Escherichia coli O157 based on
      Multiple-Locus Variable-Number Tandem-Repeats Analysis (MLVA).
AB  - BACKGROUND: The ability to react early to possible outbreaks of Escherichia coli
      O157:H7 and to trace possible sources relies on the availability of highly
      discriminatory and reliable techniques. The development of methods that are fast
      and has the potential for complete automation is needed for this important
      pathogen. METHODS: In all 73 isolates of shiga-toxin producing E. coli O157
      (STEC) were used in this study. The two available fully sequenced STEC genomes
      were scanned for tandem repeated stretches of DNA, which were evaluated as
      polymorphic markers for isolate identification. RESULTS: The 73 E. coli isolates
      displayed 47 distinct patterns and the MLVA assay was capable of high
      discrimination between the E. coli O157 strains. The assay was fast and all the
      steps can be automated. CONCLUSION: The findings demonstrate a novel high
      discriminatory molecular typing method for the important pathogen E. coli O157
      that is fast, robust and offers many advantages compared to current methods.

PMID- 14664723
TI  - A new reverse transcription-polymerase chain reaction method for accurate
      quantification.
AB  - BACKGROUND: Reverse transcription-polymerase chain reaction (RT-PCR) is a very
      sensitive technique to measure and to compare mRNA levels among samples. However,
      it is extremely difficult to maintain linearity across the entire procedure,
      especially at the step of PCR amplification. Specific genes have been used as
      baseline controls to be co-amplified with target genes to normalize the
      amplification efficiency, but development or selection of reliable controls
      itself has created a new challenge. RESULTS: Here, we describe a new quantitative
      RT-PCR to compare two mRNA samples directly without the requirement of synthetic
      control DNAs for reference. First, chimeric RT primers carrying gene-specific and
      universal PCR priming sequences with or without a linker for size distinction
      were utilized to generate cDNAs. The size-different cDNAs were then combined in a
      single reaction for PCR amplification using the same primer set. The two
      amplified products were resolved and detected with gel electrophoresis and
      fluorescence imaging. Relative abundance of the two products was obtained after a
      baseline correction. CONCLUSION: This methodology is simple and accurate as
      indicated by equal amplification efficiency throughout PCR cycling. It is also
      easily implemented for many existing protocols. In addition, parameters affecting
      RT linearity are characterized in this report.

PMID- 14664724
TI  - Sex difference in response to stress by lunar month: a pilot study of four years'
      crisis-call frequency.
AB  - BACKGROUND: This study is in response to the question of whether the moon can
      influence daily levels of stress. METHOD: Four years of telephone-call frequency
      data were obtained from a single crisis-call centre. We used the method of lunar
      day numbers 1 to 29 for analysis. We also tested the concept of 'strong moons' as
      occurring when the Sun was near to the lunar-node axis. RESULTS: An increase in
      calls was recorded from females and a decrease in calls by males during the new
      moon period, suggesting a sex difference in response, and there were
      proportionally more calls by males a fortnight later. A comparable swing in the
      male/female call-ratio on a weekly basis over Fridays and Saturdays was noted.
      Limitations of staffing at the call-centre prohibited comment on seasonal
      correlations. CONCLUSION: Lunar-related studies of stress should endeavour to
      separate the data by sex or the effect can be lost. Distress-calls by women were
      more strongly linked to the lunar month than were those by men.

PMID- 14664725
TI  - Cross-sectional survey of users of Internet depression communities.
AB  - BACKGROUND: Internet-based depression communities provide a forum for individuals
      to communicate and share information and ideas. There has been little research
      into the health status and other characteristics of users of these communities.
      METHODS: Online cross-sectional survey of Internet depression communities to
      identify depressive morbidity among users of Internet depression communities in
      six European countries; to investigate whether users were in contact with health
      services and receiving treatment; and to identify user perceived effects of the
      communities. RESULTS: Major depression was highly prevalent among respondents
      (varying by country from 40% to 64%). Forty-nine percent of users meeting
      criteria for major depression were not receiving treatment, and 35% had no
      consultation with health services in the previous year. Thirty-six percent of
      repeat community users who had consulted a health professional in the previous
      year felt that the Internet community had been an important factor in deciding to
      seek professional help. CONCLUSIONS: There are high levels of untreated and
      undiagnosed depression in users of Internet depression communities. This group
      represents a target for intervention. Internet communities can provide
      information and support for stigmatizing conditions that inhibit more traditional
      modes of information seeking.

PMID- 14664726
TI  - Pain, depression, and fatigue in cancer.

PMID- 14664727
TI  - Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper-
      a review.
AB  - A new anticopper drug, tetrathiomolybdate (TM), developed for Wilson's disease,
      is a very promising antiangiogenic agent. Copper levels lowered into an
      antiangiogenic window by TM have shown efficacy against cancer in a variety of
      animal models as well as in patients. The only significant toxicity so far
      results from overtreatment and excessive bone marrow depletion of copper. The
      resulting anemia and/or leukopenia is easily treatable by dose reduction or drug
      holiday. The underlying concept for TM efficacy as an anticancer agent is that
      when the body's copper status is in the window, cellular copper needs are met and
      toxicity is avoided. Copper status is relatively easily monitored by following
      serum ceruloplasmin, a copper-containing protein secreted by the liver at a rate
      dependent upon the amount of copper in the liver available to incorporate into
      the protein. The authors speculate that the copper level is a primitive
      angiogenesis and growth-signaling regulator that has been retained throughout
      evolution.

PMID- 14664728
TI  - Review of vitamin E and selenium in the prevention of prostate cancer:
      implications of the selenium and vitamin E chemoprevention trial.
AB  - The National Cancer Institute in cooperation with the Southwest Oncology Group
      has begun one of the largest prostate cancer prevention studies to date, the
      Selenium and Vitamin E Chemoprevention Trial (SELECT). The purpose of this
      article is to review the evidence and discuss the individual antioxidant
      compounds under study. The authors comprehensively reviewed the peer-reviewed
      literature on the chemoprevention of prostate cancer with emphasis on the
      antioxidants vitamin E and selenium. The credible leads for the primary
      prevention of prostate cancer using selenium and vitamin E have emerged as
      secondary findings from randomized controlled trials with corroborative evidence
      from observational and in vitro studies. Selenium and vitamin E are widely
      available compounds that are safe if taken in moderation, with relatively few
      adverse effects. The evidence in support of the antioxidants in the primary
      prevention of prostate cancer is promising, and the next step in definitively
      answering the question has been addressed by the investigators of SELECT. The
      SELECT study will define the role of the antioxidants selenium and vitamin E in
      the prevention of prostate cancer; complete data from the study will be available
      in 12 years.

PMID- 14664729
TI  - Exploratory studies of Qigong therapy for cancer in China.
AB  - The authors reviewed more than 50 studies of qigong therapy for cancer in China,
      in 3 categories: clinical studies on cancer patients, in vitro studies on
      laboratory-prepared cancer cells, and in vivo studies on cancer-infected animals.
      Most of the clinical studies involved observation of cancer patients' self
      practice of qigong. Although no double-blind clinical trials were found among
      patient studies, many had a control. The qigong groups showed more improvement or
      had a better survival rate than conventional methods alone. In vitro studies
      report the inhibitory effect of qi emission on cancer growth, and in vivo studies
      find that qigong-treated groups have significantly reduced tumor growth or longer
      survival among cancer-infected animals. However, there is much room for
      improvement in these studies, and some require replication to verify the
      findings. Qigong therapy is an area that is often neglected by mainstream
      medicine and research, but our review strongly suggests that qigong deserves
      further study as a supplement to conventional cancer treatment.

PMID- 14664730
TI  - Attachment and cancer: a conceptual integration.
AB  - Cancer traditionally has been explained by the biomedical model; however, it is
      limited in comprehensively accounting for all factors in this disease. Recently,
      it has been suggested that a broader theoretical framework that includes
      psychosocial components in cancer is needed to complement the traditional
      approach. The purpose of this article, therefore, is to explore the utility of
      attachment theory as a biopsychosocial model of both development and health.
      Attachment, a developmental theory, explains how repeated interactions between
      caregiver and child in the early years establish lifelong psychosocial,
      physiological, affective, and cognitive patterns as well as enduring patterns of
      stress response to threat or illness. Despite attachment theory's biopsychosocial
      foundation, the application of attachment security as a factor in physical health
      and psychosomatic medicine is relatively recent. The current work reviews
      attachment theory and psychosocial literature with regard to cancer and follows
      with a novel attempt to conceptually integrate both bodies of literature. A
      concluding integrative model of attachment theory and the type C behavior pattern
      is provided to illustrate potential links and integrative processes that may lead
      to disease resilience or vulnerability.

PMID- 14664732
TI  - Connecting the dots linking mind, behavior, and disease: the biological
      concomitants of coping patterns: commentary on "Attachment and Cancer: A
      Conceptual Integration".

PMID- 14664733
TI  - Integrative tumor board: recurrence of ovarian cancer.

PMID- 14664734
TI  - Cancer, depression, and St. John's wort.

PMID- 14664735
TI  - Editorial: On psycho-oncology, lycopene and the Noni fruit.

PMID- 14664736
TI  - From Polynesian healers to health food stores: changing perspectives of Morinda
      citrifolia (Rubiaceae).
AB  - Morinda citrifolia L (noni) is one of the most important traditional Polynesian
      medicinal plants. Remedies from isolated Polynesian cultures, such as that of
      Rotuma, illustrate traditional indications that focus upon leaves, roots, bark,
      and green fruit, primarily for topical ailments. Anecdotally collected Hawaiian
      remedies that employ noni fruit illustrate changing usage patterns with shifts in
      recent times to preparation of juice made of ripe or decaying fruit. Ralph M.
      Heinicke promoted a wide range of claims about noni, and these seem to have
      fueled much of the current commercial interest in the plant. Recent studies of
      the proliferation of commercial products have shown that noni product
      manufacturers are promoting a range of therapeutic claims. These claims are based
      upon traditional Polynesian uses, Heinicke's ideas, and fragments of recent
      scientific studies including the activity of noni in the treatment of cancer. A
      review is provided of recent studies of potential anticancer activity of noni
      fruit. While noni's anticancer potential is still being explored, it continues to
      be widely used by Polynesians and non-Polynesians alike for both traditional and
      newly hypothesized indications.

PMID- 14664737
TI  - Can the consumption of tomatoes or lycopene reduce cancer risk?
AB  - Lycopene, a natural antioxidant found predominantly in tomato products, is
      attracting attention as a cancer prevention agent. Serum and dietary lycopene
      levels have been found to be inversely related to the incidence of several types
      of cancer, including prostate cancer. Although the antioxidant properties of
      lycopene are thought to be primarily responsible for its apparent beneficial
      effects, other mechanisms may also be involved. We outline the possible
      mechanisms of action of lycopene and review the current findings of in vitro and
      in vivo studies in cancer prevention and to some extent treatment. We examine the
      epidemiologic evidence regarding consumption of tomato and tomato products with
      the risk of cancer at various sites. Data suggest lycopene may account for or
      contribute to chemoprevention, but this hypothesis requires further study.
      Numerous other potentially beneficial compounds are present in tomatoes and
      complex interactions among multiple components may contribute to the anticancer
      properties of tomatoes.

PMID- 14664738
TI  - Psycho-Oncology 2001: papers from the 4th Comprehensive Cancer Care Conference,
      October 19-21, 2001.

PMID- 14664739
TI  - Change is complex: rethinking research on psychosocial interventions and cancer.
AB  - The widely discussed 1989 study by Spiegel and colleagues, which suggested that a
      psychosocial group intervention affected survival in metastatic breast cancer,
      was not replicated by Goodwin and colleagues in 2001. We analyze methodological
      issues in both studies, including issues of sampling, randomization,
      interpretation, and the adequacy and validity of psychosocial constructs and
      measures to assess hypothesized ingredients of change. The notion of
      psychogenicity is introduced, conceived as the ability of psychosocial
      interventions to elicit changes hypothesized to be linked to desired medical
      outcomes. These considerations lead to the conclusion that there is insufficient
      evidence to be able to generalize from either study for or against the notion
      that psychosocial interventions can affect survival in breast cancer. The failure
      to incorporate into research designs a comprehensive understanding of how coping
      patterns and related factors may interact with psychosocial interventions to
      influence cancer progression, and to address hypothesized mediating mechanisms is
      discussed. Finally, strategies are proposed for future biopsychosocial and
      intervention research in the field of biopsychooncology.

PMID- 14664740
TI  - Fighting for life: a qualitative analysis of the process of psychotherapy
      assisted self-help in patients with metastatic cancer.
AB  - This exploratory study is an attempt to define psychological attributes related
      to longer survival in patients with metastatic cancers. Previous published
      analyses have been limited in two ways. First, they have almost always been
      carried out on patients not receiving therapy; we have followed people receiving
      a year of group therapy, on the assumption that if mental qualities are to affect
      cancer progression, substantial mental change would be needed to alter the
      established balance between the cancer cells and host regulatory mechanisms.
      Second, the methods typically used to characterize patients' psychology have been
      self-report inventories, and many decades of research with such methods have
      largely failed to produce a consensus on what mental qualities, if any, promote
      survival. By contrast, we have used qualitative methods, allowing a much more in
      depth analysis of the patients, without preliminary assumptions as to what would
      be important. The present report describes the results of a detailed qualitative
      analysis of data collected from 22 participants over a year of weekly group
      therapy. Using grounded methods, categories were derived from the extensive
      verbal data (comprising patients' written homework and therapists' notes), and
      linked in a model of change. By applying ratings to some of these categories, and
      combining these ratings, we derived a quantitative estimate of patients'
      "involvement in self-help." Rankings on degree of involvement corresponded quite
      closely with the quality of patients' experience and with their survival
      duration. There was a great range in degree of involvement, and various
      subgroupings could be discerned. Nine of the participants were classed as "highly
      involved," meaning that they devoted regular daily time, often several hours, to
      such self-help strategies as relaxation, mental imaging, meditation, cognitive
      monitoring and journalling. All but 1 of these patients enjoyed a good quality of
      life and lived at least 2 years. Two of them have remained in complete remission
      for 7 years. At the other end of the scale, 8 patients showed little application
      to the work, being either unconvinced that it would help them or hampered by
      psychological problems such as low self-esteem. None of these was rated as having
      a good quality of life, and only 1 lived more than 2 years, although, as a group,
      their medical prognoses were no more unfavorable at the onset of therapy than for
      the "high involvement" group. The different subgroups and aspects of the model
      are illustrated by representative quotations.

PMID- 14664741
TI  - Interactive Guided Imagery as a way to access patient strengths during cancer
      treatment.
AB  - In cancer care, there are 2 complementary goals of treatment: eliminating cancer
      cells and supporting the well-being and healing abilities of the patient.
      Interactive Guided Imagery(sm)(IGI) can be used to help the patient access inner
      strengths and resources when high anxiety levels may make that difficult. Three
      brief cases illustrate the use of IGI to help patients access a "big picture"
      perspective on their treatment and healing path; to find strength to persevere in
      their treatment course; and to help make a difficult decision. In all 3 cases,
      there are multiple personal benefits of the imagery that continued to be of
      importance throughout the course of each patient's treatment.

PMID- 14664742
TI  - Spiritual correlates of functional well-being in women with breast cancer.
AB  - Breast cancer is the most common cancer in women in the United States and
      constitutes a major source of medical and psychological morbidity. The
      psychosocial sequelae, while not always severe, can last up to a year after
      diagnosis. This may be a time when spiritual and social resources become
      important. It is known that practical and emotional support during treatment for
      breast cancer benefits the patient's mood and quality of life, but it is unclear
      as to how spirituality and spiritual well-being may benefit the patient. This
      study examined this question by exploring the relationships between spirituality,
      spiritual well-being, physical well-being, functional well-being, mood, and
      adjustment style in a sample of 191 women recently diagnosed with breast cancer
      or who had metastatic cancer. The women were asked to complete questionnaires
      pertaining to the above topics at enrollment to a group intervention study.
      Measures of spirituality, spiritual well-being, physical well-being, functional
      well-being, mood, and adjustment style taken at the same point in time were then
      correlated with each other. There were more significant correlations of
      spirituality and spiritual well-being with functional well-being than physical
      well-being, but items pertaining to meaning and peace tended to correlate
      significantly with physical well-being. Spirituality also correlated
      significantly with several coping styles, but not avoidance as has been
      previously suggested. Regression analyses were also performed to find the best
      combination of variables to predict physical and functional well-being. A
      combination of social well-being and several questions pertaining to peacefulness
      accounted for 18% of the variance in physical well-being. However, a combination
      of social well-being and the spiritual scales accounted for 46% of the variance
      in functional well-being. When the spiritual scales were examined alone, they
      accounted for 40% of the variance in functional well-being. The results of this
      study confirm the importance of spirituality and spiritual well-being in both
      physical and functional well-being. Asking patients about the role of
      spirituality in their lives may be a useful marker to predict patient's ability
      to cope with stress in their lives and of their quality of life.

PMID- 14664743
TI  - Principles for applying traditional chinese medicine to cases of cancer.
AB  - Traditional Chinese herbology uses a system of categorizing clusters of symptoms
      and signs to differentially assess the presence or absence of syndromes for which
      effective herbal formulas and methods are known. This system can be useful in
      detecting and counteracting some of the severe systemic and metabolic imbalances
      that commonly occur in cases of cancer. Basic theory and terminology is outlined,
      with comparisons between the empirical concepts of Chinese herbology and their
      approximate physiological correlates.

PMID- 14664745
TI  - Editorial: Integrative cancer treatment in the 21st century.

PMID- 14664744
TI  - Integrative tumor board: Advanced breast cancer.

PMID- 14664746
TI  - Nutritional and botanical modulation of the inflammatory cascade--eicosanoids,
      cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy.
AB  - Emerging on the horizon in cancer therapy is an expansion of the scope of
      treatment beyond cytotoxic approaches to include molecular management of cancer
      physiopathology. The goal in these integrative approaches, which extends beyond
      eradicating the affected cells, is to control the cancer phenotype. One key new
      approach appears to be modulation of the inflammatory cascade, as research is
      expanding that links cancer initiation, promotion, progression, angiogenesis, and
      metastasis to inflammatory events. This article presents a literature review of
      the emerging relationship between neoplasia and inflammatory eicosanoids (PGE2
      and related prostaglandins), with a focus on how inhibition of their synthesizing
      oxidases, particularly cyclooxygenase (COX), offers anticancer actions in vitro
      and in vivo. Although a majority of this research emphasizes the pharmaceutical
      applications of nonsteroidal anti-inflammatory drugs and selective COX-2
      inhibitors, these agents fail to address alternate pathways available for the
      synthesis of proinflammatory eicosanoids. Evidence is presented that suggests the
      inhibition of lipoxygenase and its by-products-LTB4, 5-HETE, and 12-HETE
      represents an overlooked but crucial component in complementary cancer therapies.
      Based on the hypothesis that natural agents capable of modulating both
      lipoxygenase and COX may advance the efficacy of cancer therapy, an overview and
      discussion is presented of dietary modifications and selected nutritional and
      botanical agents (notably, omega-3 fatty acids, antioxidants, boswellia,
      bromelain, curcumin, and quercetin) that favorably influence eicosanoid
      production.

PMID- 14664748
TI  - Integrative tumor board: Esophageal cancer.

PMID- 14664747
TI  - Radioprotective effects of vitexina for breast cancer patients undergoing
      radiotherapy with cobalt-60.
AB  - Vitexina, a product containing the flavonoid vitexin as the main component, is
      derived from a plant, Vigna radiata (L.), that has been traditionally used in
      Vietnam for detoxification. This remedy is also used to treat the symptoms of
      conditions classified as "hot" in traditional medicine. The present study is a
      randomized, placebo-controlled comparative clinical trial for investigating the
      radioprotective effects of Vitexina for breast cancer patients undergoing
      radiotherapy with cobalt-60. No relevant weight loss, (even weight gain),
      occurred in 70% of patients in the Vitexina group, whereas 73% of the placebo
      group lost 1 to 2 kg of weight after 6 weeks of radiation therapy. The
      administration of Vitexina produced a significantly protective effect in
      peripheral blood cells in amount and in lymphocyte blast-transformation function.
      Condition of hot was observed in almost all cancer patients in this study by
      tongue examination. Hot condition did not change in the Vitexina group, but the
      incidence of hot and extreme hot cases were significantly increased in the
      placebo group after 6 weeks of radiation therapy. The results suggest that
      application of medicinal plants of the "clearing heat and detoxification"
      classification as an adjuvant would be a potential solution in integrative cancer
      therapy.

PMID- 14664749
TI  - Group psychological therapy: an integral part of care for cancer patients.
AB  - Adjuvant psychological therapy can help cancer patients in 2 main ways. It has,
      first, a well-documented capacity to alleviate distress and thus improve quality
      of life. However, if this kind of assistance is to be made available to the
      majority of cancer patients, a number of problems need to be solved:
      administrators need to become aware of the evidence for efficacy of psychosocial
      care for cancer patients; the treatment needs to be advocated in a manner that
      would benefit patients rather than being left to the patient to request it; and,
      for reasons of economy, large, classroom-style, psychoeducational classes may
      need to be offered in place of small support groups. Furthermore, to allow for
      individual differences in preferences and abilities, a variety of modes of help
      should ideally be made available. The author discusses how the provision of
      coping strategies can be organized in a progressive way to encourage development
      of greater coping skills. An example of such a stepwise program is given, all
      aspects of which have been researched and made available in manuals over some 20
      years. The possibility of prolonging life with this kind of therapy is still
      controversial. While randomized controlled trials have become the method of
      choice to investigate this question, reasons are given for strongly preferring
      more exploratory modes of research at the present early stage of knowledge. The
      central task is seen as understanding the states of mind that promote healing or
      longer life, something that cross-sectional, psychometric research has not been
      able to accomplish. As an alternative, prospective, longitudinal designs are
      needed, with detailed interview-style analyses of patients' mental attributes. An
      example is given of one such study. Furthermore, it is suggested that we consider
      much more intensive therapies of this kind, since the impact of mind on body will
      logically be related to the extent of psychological change experienced.

PMID- 14664750
TI  - A model program: exercise intervention for cancer rehabilitation.
AB  - Recent advances in cancer detection and treatment have resulted in an increase in
      the survival rate of individuals diagnosed with cancer. The increased survival
      rate brings new challenges for increasing the quality of life for cancer
      survivors. Debilitating side effects can result from the cancer itself and the
      cancer treatment. The negative effects lead to decreased functional (work)
      capacity, increased fatigue, and debilitating muscular weakness. There have been
      very positive benefits seen from the use of individualized prescriptive exercise
      intervention in alleviating these cancer treatment related symptoms. The role of
      exercise intervention as a complementary therapy is just emerging. Studies have
      shown that exercise decreases the amount of fatigue, improves functional
      capacity, increases immune function, and leads to improved quality of life. The
      effects of cancer and cancer treatments require that an exercise intervention
      program be well based in sound scientific principles. The exercise intervention
      needs to be carefully structured and controlled. All patients should be assessed
      and reassessed to evaluate progress. A cancer exercise specialist should closely
      monitor the exercise regime. Exercise should involve a whole-body approach that
      emphasizes all areas of fitness. Exercise therapy for cancer patients is a new
      and exciting area that will continue to grow as medical professionals realize the
      necessity for post-cancer treatment intervention to improve quality of life.

PMID- 14664751
TI  - Clinical corner: herb-drug interactions in cancer chemotherapy: theoretical
      concerns regarding drug metabolizing enzymes.
AB  - Interactions between herbal medicines and conventional drugs have recently been
      reported; the most significant herb with such drug interactions is Saint John's
      wort, an inducer of cytochrome P450 3A3/4, an enzyme responsible for clearance of
      many clinically important drugs from the body. Foods (especially grapefruit) and
      habits or lifestyle factors such as smoking or alcohol consumption may also alter
      the metabolism of drugs through effects on the cytochrome P450 system. The
      authors review here the functioning of the drug-metabolizing enzymes and discuss
      their particular significance in cancer chemotherapy treatment. They then present
      the herbal medicines, foods, and lifestyle factors that induce or inhibit drug
      metabolizing enzymes that are important for both cancer chemotherapy drugs and
      drugs used adjunctively in cancer treatment. It is notable that no actual herb
      drug interactions have been reported clinically in cancer treatment, and their
      potential for interaction still must be regarded as theoretical. Although some
      chemotherapy patients may be interested in taking herbal medicines that could
      potentially interact with cancer chemotherapy agents, it may be wise to counsel
      them to use other means of addressing the problems for which they use specific
      herbs during the time they receive chemotherapy.

PMID- 14664752
TI  - Point-counterpoint: soy intake for breast cancer patients.

PMID- 14664754
TI  - Is it time for oncologists to modify their laissez-faire attitude toward
      alternative/complementary 'drug therapy'?

PMID- 14664755
TI  - Central nervous system toxicity from cancer treatment.
AB  - Neurologic complications of cancer therapy are an increasingly important concern
      in patient management. Improvements in systemic therapies and increasing use of
      local treatments to target such specific tumor sites as brain or leptomeningeal
      metastases have resulted in increased incidence of treatment toxicity in the
      central nervous system (CNS). Recognition of specific treatment-related
      toxicities, and more importantly, differentiation of treatment toxicity from
      reversible causes of neurologic dysfunction, are critical. This article reviews
      the evaluation and treatment of major CNS toxicities related to cancer treatment
      and conditions that present with similar signs and symptoms. The three most
      common of these, alterations in cognition and consciousness, seizures, and
      cerebellar dysfunction, are discussed. Prompt recognition of these problems and
      their causes will have an impact on patient care in all areas of oncology.

PMID- 14664756
TI  - Peripheral neuropathy and cancer.
AB  - Peripheral neuropathy has a major impact on quality of life and may limit the
      amount of treatment patients can receive. Neurotoxic agents are used increasingly
      in oncologic practice, yet clinicians are often unaware of the protean
      manifestations of neuropathy and find its management troubling. Recent knowledge
      about the mechanisms of neuropathic disease and new treatments may help to
      minimize the impact of neuropathy on this vulnerable patient population.

PMID- 14664757
TI  - Neurologic paraneoplastic syndromes.
AB  - Paraneoplastic disorders can affect any part of the central or peripheral nervous
      system. Although relatively uncommon, these disorders are a significant cause of
      severe neurologic disability among cancer patients. Many paraneoplastic disorders
      are believed to be caused by an autoimmune response directed against shared
      neural tumor antigens. This article summarizes the clinical features, possible
      autoimmune pathophysiology, and management issues for patients with
      paraneoplastic disorders.

PMID- 14664758
TI  - Letrozole in postmenopausal women after five years on tamoxifen.

PMID- 14664759
TI  - Statistics in clinical trials.
AB  - Statistical developments over the past several years are described in this
      review. Efforts in phase I studies have focused on efficient estimation of
      maximum tolerated dose. Issues investigated for phase II trials include
      incorporation of multiple endpoints and randomization. For phase III trials,
      methods to reduce time or use the sample size more efficiently have been
      investigated. However, design innovations come with costs, including possible
      increased risk of incorrect conclusions. Other recent challenging statistical
      developments in clinical trials relate to use of complementary outcomes such as
      quality of life and to associated biologic questions, including the emergence of
      the field of genomics.

PMID- 14664760
TI  - A role for antiangiogenic therapy in breast cancer.
AB  - The success of the angiogenesis inhibitor bevacizumab, the vascular endothelial
      growth factor antagonist that was recently shown to significantly improve the
      survival of patients with metastatic colon cancer when administered in
      combination with conventional chemotherapy, has provided proof of principle in
      clinical trials that antiangiogenesis can be an important strategy in the
      treatment of cancer. This report reviews the contemporary therapeutic approaches
      for breast cancer, the essential role that angiogenesis plays in the initiation
      and progression of this disease, and the strategies that should be considered to
      make antiangiogenic therapy a successful component of breast cancer treatment.

PMID- 14664761
TI  - Metronomic therapy for breast cancer.
AB  - Conventional cytotoxic chemotherapeutic drugs treat cancer either by direct
      killing or by inhibition of growth of cycling tumor cells. In addition, evidence
      suggests that cytotoxic agents may inhibit tumor growth through an antiangiogenic
      mechanism. "Metronomic" or frequent continuous administration of the same
      chemotherapeutic agents at lower doses may optimize their antiangiogenic
      properties. The effectiveness of metronomic chemotherapy regimens can be improved
      significantly by concurrent administration of antiangiogenic, endothelial
      specific drugs. Preclinical studies have shown that integrating chemotherapy with
      antiangiogenic drugs can improve efficacy and circumvent the toxicity and drug
      resistance associated with standard or high-dose chemotherapy. Preliminary
      clinical studies have shown similar results. Further confirmation of this concept
      is required with randomized, controlled clinical trials.

PMID- 14664762
TI  - Management of patients with locally advanced breast cancer.
AB  - Increased breast health awareness has led to earlier stage distribution among
      breast cancer patients in the United States; however, locally advanced tumors
      remain a major source of morbidity and mortality. Early attempts to control this
      high-risk pattern of disease with surgery or radiation alone were met with
      disappointingly high rates of treatment failure in locoregional and distant
      sites. Multimodality strategies represent a major advance in management of these
      difficult cancers. The current standard of care is neoadjuvant chemotherapy to
      improve operability, followed by breast and axillary surgery (including
      lumpectomy for appropriately selected patients). Following surgery, decisions
      regarding the need for additional chemotherapy with or without locoregional
      irradiation are made based on stage at presentation, response to systemic
      therapy, and surgical-pathology findings. Recommendations for adjuvant endocrine
      therapy are based on hormone receptor status. Studies of these tumors have
      confirmed that primary response to induction therapy is an excellent surrogate
      marker of success in eradicating micrometastases, as patients experiencing a
      complete pathologic response have a statistically significant survival advantage.
      Ongoing investigations of locally advanced breast cancer include studies of
      systemic chemotherapy with or without neoadjuvant endocrine regimens that
      increase the complete pathologic response rate, and correlation with outcome;
      integration of lymphatic mapping and sentinel lymph node biopsy into clinical
      trials; and defining the optimal extent of locoregional irradiation in patients
      who experience a strong response to neoadjuvant treatment.

PMID- 14664763
TI  - The role of positron emission tomographic imaging in breast cancer.
AB  - Studies have shown that deoxy-2-fluorodeoxyglucose ((18)FDG) positron emission
      tomography (PET) has limited value in detecting primary tumors and axillary lymph
      node involvement in breast cancer. PET is most successful when it is used to
      evaluate locally advanced breast tumors. Identification of smaller, earlier-stage
      tumors and noninvasive or lobular tumors has been suboptimal. Because of several
      factors, PET should not replace standard techniques for evaluation of breast
      cancer, especially for micrometastasis. However, PET can provide invaluable
      information about disease extent, recurrent disease, and distant metastases, and
      this information can affect treatment decisions. (18)FDG PET can also facilitate
      the differentiation of therapy responders from nonresponders, allowing treatment
      regimen changes at an earlier stage.

PMID- 14664764
TI  - Ductal lavage in the screening of high-risk women.
AB  - Due to the high incidence of breast cancer and the excessively high false
      positive rate of current screening technologies, adjunctive risk assessment
      measures are needed. Nipple aspiration cytologic analysis and random fine-needle
      aspirations have been proposed; however, ductal lavage and cytologic analysis of
      the effluent is a more sensitive and specific test. The dilemma lies in what
      should be done subsequent to a ductal lavage yielding malignant or atypical
      cells. The procedures and potential management strategies are discussed.

PMID- 14664765
TI  - Myasthenic Crisis.
AB  - Myasthenia gravis is the most common disorder of the neuromuscular junction.
      Myasthenia crisis, defined as respiratory failure requiring mechanical
      ventilation in myasthenia gravis, is a common life-threatening complication that
      occurs in approximately 15% to 20% of patients with myasthenia gravis. The advent
      of effective mechanical ventilation, specialized neurointensive care units, and
      the widespread use of immunotherapies have substantially altered the prognosis of
      myasthenic crisis. The authors recommend more liberal intubation of patients with
      myasthenia gravis crisis; early intubation and mechanical ventilation is perhaps
      the most important step in the management of myasthenia gravis crisis. The
      authors favor an orotracheal approach for intubation, and placement of small bore
      duodenal tubes that may help decrease the risk of aspiration and may be more
      comfortable than regular nasogastric tubes for the patient. Plasma exchange is
      more effective than intravenous immunoglobulin in the treatment of myasthenia
      gravis involving respiratory failure. A randomized trial is required to confirm
      the superior efficacy of plasma exchange compared with intravenous
      immunoglobulin. In the acute setting, the role of immunosuppression and
      intravenous or intramuscular pyridostigmine remains limited and at times
      controversial. The therapy should be tailored on an individual basis using the
      best clinical judgment.

PMID- 14664766
TI  - Insecticides.
AB  - Organophosphate (OP) insecticide toxicity is the leading cause of major morbidity
      and death in the insecticides class. The clinical syndrome of OP toxicity varies
      widely, ranging from the classic cholinergic syndrome to flaccid paralysis and
      intractable seizures. The mainstays of therapy for OP-poisoned patients are
      atropine, pralidoxime, and benzodiazepines. Tachycardia is not a contraindication
      to treatment with atropine in OP toxicity. Atropine should be administered to
      alleviate respiratory distress, symptomatic bradycardia, and as an adjunct to
      benzodiazepines to alleviate seizure activity. Atropine should not be
      administered systemically to alleviate miosis. In acute OP toxicity, a continuous
      pralidoxime infusion should be considered. Intermediate syndrome and OP-induced
      delayed neuropathy may occur in select patients with OP poisoning.

PMID- 14664767
TI  - Tetanus.
AB  - Tetanus is a potentially lethal disease that is preventable with appropriate
      vaccination. The diagnosis is made exclusively on clinical criteria, and early
      recognition and treatment are essential for positive outcome. Patients should be
      monitored in the intensive care unit immediately on diagnosis. Early intubation
      and mechanical ventilation have drastically reduced the mortality from tetanus.
      Autonomic instability is associated with a high fatality rate and therefore must
      be aggressively treated. Metronidazole, human tetanus immunoglobulin, and active
      immunization should also be initiated on presentation. Because of extremely high
      metabolic demands in patients with tetanus, care must be taken to provide
      adequate nutrition and fluids. Prevention of sequelae of long-term critical
      illness, such as nosocomial pneumonia and deep venous thrombosis, are also
      important for achieving good outcomes.

PMID- 14664768
TI  - Transient Vision Loss.
AB  - Transient vision loss often presents a diagnostic dilemma and may occur in many
      different settings. Episodic vision loss is a common complaint and the physician
      must distinguish whether the transient vision loss is benign or representative of
      a more serious underlying condition. Common causes of transient vision loss
      include ischemia and primary ocular pathology. Ischemic causes of vision loss
      include retinal vascular disease, intermittent optic nerve vascular compromise,
      or cerebrovascular disease. Many pathologic ocular processes may lead to
      transient vision loss, including tear film abnormalities and corneal diseases.
      The authors discuss the clinical presentation and management of transient vision
      loss, with special attention on characteristics that differentiate vascular
      disease from primary ocular pathology.

PMID- 14664769
TI  - Giant Cell Arteritis.
AB  - Patients with a suspected diagnosis of giant cell arteritis (GCA) should be
      started on high-dose corticosteroid therapy without delay. A temporal artery
      biopsy should be performed after initiation of therapy to confirm the diagnosis.
      Patients with acute visual or neurologic symptoms present a neuro-ophthalmic
      emergency. Therapy should be initiated immediately with high-dose intravenous
      methylprednisolone sodium succinate and followed by high-dose oral prednisone.
      Treatment may begin with high-dose oral prednisone in patients without visual or
      neurologic symptoms. Calcium, vitamin D, and peptic ulcer prophylaxis should
      accompany steroid therapy, as indicated. The following treatments should be
      considered for patients with suspected GCA and acute visual or neurologic signs
      or symptoms: intravenous methylprednisolone sodium succinate (250 mg
      intravenously every 6 hours) should be given for 3 days, followed by oral
      prednisone (80 mg per day or 1 mg/kg) for 4 to 6 weeks. Prednisone should then be
      tapered by 10 mg per day every month. Most patients require 1 year of therapy to
      avoid relapse. Taper and duration should be modified according to erythrocyte
      sedimentation rate, C-reactive protein, and signs and symptoms of GCA.
      Rheumatologic consultation and follow-up is often helpful for these patients. For
      patients with suspected GCA and no acute visual or neurologic signs or symptoms,
      therapy may begin directly with oral prednisone (80 mg per day or 1 mg/kg) with
      same taper and duration based on laboratory values and clinical signs and
      symptoms.

PMID- 14664770
TI  - Acute Hearing Loss.
AB  - Acute hearing loss (AHL) is a medical urgency. The management of patients
      presenting with sudden deafness involves detecting the causal mechanism and
      administering emergency therapeutic drugs to restore hearing by minimizing the
      period of cellular ischemia to the inner ear. Acute management of AHL consists of
      administering a 10-day course of high-dose corticosteroids (prednisone 60 to 80
      mg) until a cause can be established. Magnetic resonance imaging with gadolinium
      is indicated, with a study dedicated to the internal auditory canals. The natural
      history of idiopathic AHL is characterized by spontaneous improvement in two
      thirds of patients. Maximum improvement occurs within 2 weeks of onset of AHL. In
      the vast majority of patients (>90%), the AHL is idiopathic. For an identifiable
      etiology, the treatment is specific and may consist of stopping ototoxic
      medications, repair of perilymphatic fistulas, administering antimicrobial agents
      for viral or bacterial infections, correction of metabolic imbalances, management
      of stroke, and possible surgery for cerebellopontine angle tumors. Management of
      idiopathic AHL is controversial. Various therapeutic agents, such as
      vasodilators, diuretics, anticoagulants, plasma expanders, contrast agents, and
      carbogen inhalation, have been tried in single therapy or as a combination
      therapy. The empiric use of these drugs is mainly based on improving the blood
      circulation and restoring the oxygen tension to the inner ear. The use of
      interventional procedures, such as low-density lipoprotein apheresis as well as
      newer drug delivery systems for corticosteroids, and immunosuppressive agents
      have opened new options in the treatment of AHL secondary to immune-mediated
      diseases of the inner ear. Prognosis for AHL is best when patients are seen
      early, begin recovery within 2 weeks, and have a mild hearing loss (<90 dB) with
      upward-sloping audiograms. Greater than 90 dB of hearing loss along with flat or
      down sloping audiogram, advanced age, and presence of vertigo are adverse
      prognostic factors for recovery of hearing loss.

PMID- 14664771
TI  - Functional Visual Loss.
AB  - Patients who present with visual loss that cannot be explained by organic lesions
      represent a wide spectrum of patients from those with no physiologic problem to
      those patients who have a true underlying condition. Regardless of where a
      patient falls within this spectrum, all patients need to be approached with a
      clinical evaluation to ensure that no underlying physiologic deficit exists.
      After excluding organic causes with appropriate examination and testing, a
      patient's visual loss still should not be labeled as functional until it is
      proven that they can see better than they claim to see. Only after convincingly
      demonstrating better vision can the physician begin to consider treatment options
      to help the patient's vision recover. Although functional visual loss places the
      physician in an unusual adversarial position of refuting a patient's symptoms,
      exposing the patient in a confrontational manner rarely helps. Instead, an
      approach that allows patients to resolve the symptoms on their own through
      reassurance and support often leads to successful restoration of vision.
      Reassurance that their condition is not serious, and may recover with time,
      allows patients to slowly admit their vision is improving without ever suggesting
      that the concern and medical attention they sought was unwarranted.

PMID- 14664772
TI  - Visual Hallucinations.
AB  - Neurologists and ophthalmologists should be familiar with the causes and
      treatment of visual hallucinations so that they are able to reassure patients and
      minimize the anguish associated with untreated visual hallucinations.
      Hallucinations are under-reported by patients because of the perceived
      psychiatric implication or because of poor insight into the unreal nature of the
      hallucinations. In the appropriate setting, physicians should specifically
      inquire about hallucinations as well as initiate medical treatment. Visual
      hallucinations have many etiologies and are associated with a variety of
      disorders. Identification of the associated disorder or cause is necessary to
      determine the appropriate treatment. Causes and associated disorders include
      ocular phenomena, migraine, seizures, visual loss (ie, release hallucinations),
      neurodegenerative disorders, midbrain injury, alcohol and drug effects,
      narcolepsy, post-traumatic stress disorder, and psychosis. Therapeutic treatment
      should be directed at the associated disorder or etiology. For instance,
      antiepileptic drugs may be appropriate for patients with irritative phenomena
      such as seizures and visual aura of migraine. Depending on the cause, other
      agents are available and include neuroleptics, cholinesterase inhibitors, and
      acetazolamide. Well-designed, randomized, controlled clinical trials regarding
      treatment of visual hallucinations associated with various disorders are lacking.
      Although complete resolution of visual hallucinations can be difficult, even
      minimal improvement may be symptomatically beneficial.

PMID- 14664773
TI  - Triglyceride and coronary heart disease mortality in a 24-year follow-up study in
      Xi'an, China.
AB  - PURPOSE: To study whether serum triglyceride (TG) was associated with coronary
      heart disease (CHD) mortality. METHODS: A cohort analytic study carried out in a
      machinery factory in Xi'an, China on 1696 subjects aged 35 years or above (1124
      men and 572 women) examined in 1976 and followed up till 2000. RESULTS: At
      baseline, the mean serum total cholesterol (TC) and triglyceride (TG) was 4.64
      and 1.16 mmol/L in men, 4.62 and 1.10 mmol/L in women, respectively. Three
      hundred six (239 men, 67 women) had died within 37,781 person-years of follow-up,
      with 49 CHD deaths (36 male, 13 female). The relative risk (95% confidence
      interval) of CHD mortality per mmol/L increase in TG was 2.13 (1.46-3.17) after
      adjusting for age, marital status, occupation, education, systolic blood pressure
      and TC. Dose-response relationship between TG levels by tertiles and CHD risk was
      found. Stratified analyses showed TG was an independent predictor for CHD
      mortality in subjects with lower or higher TC. CONCLUSIONS: Chinese had lower
      levels of TC and TG than Western populations. This study provides new evidence
      that TG is an independent risk factor of CHD in subjects with lower or higher TC
      levels, and supports the lowering of cut-off value for elevated triglyceride.

PMID- 14664774
TI  - Birth weight and carotid intima-media thickness: new perspectives from the
      atherosclerosis risk in young adults (ARYA) study.
AB  - PURPOSE: Although intrauterine growth retardation (IUGR) is associated with
      increased risk of cardiovascular disease (CVD) in adult life, it is unclear
      whether the relationship is present at younger ages. Furthermore, current debate
      suggests that postnatal factors might be at least as important as prenatal
      conditions. The authors investigated whether low birth weight leads to an
      increased risk of subclinical atherosclerosis in a population-based sample of 750
      Dutch men and women, aged 27 to 30 years. METHODS: Information about birth
      characteristics was available from the original charts of the Municipal Health
      Service, Utrecht, The Netherlands. Cardiovascular risk factors were evaluated by
      a questionnaire. The extent of atherosclerosis, assessed by carotid intima-media
      thickness (CIMT), was measured in both common carotid arteries. RESULTS: Overall,
      birth weight was not related to common CIMT. However, in the lowest tertile of
      birth length an inverse association between birth weight and common CIMT was
      observed. Moreover, low birth weight was significantly associated with increased
      common CIMT in those who showed exaggerated postnatal growth. CONCLUSIONS: These
      findings suggest that low birth weight is only associated with increased common
      CIMT in young adulthood in those who experienced severe IUGR and in those who
      showed exaggerated postnatal growth.

PMID- 14664775
TI  - The role of gender in the long-term prognosis of patients with myocardial
      infarction submitted to fibrinolytic treatment.
AB  - PURPOSE: To determine the role of gender in short- and long-term survival after a
      thrombolytic-treated myocardial infarction. METHODS: A total of 686 consecutive
      patients with ST-elevation acute myocardial infarction, admitted to a single
      center and treated with intravenous streptokinase, were studied prospectively and
      consecutively. Assessment of clinical and in-hospital variables permitted
      comparison of baseline characteristics and both in-hospital and long-term
      survival between men and women. RESULTS: A significantly (odds ratio=0.48,
      P=0.009) lower 14-day mortality rate for males (8.5%) relative to females (16%)
      was noted. However, this difference became non-significant after adjustment for
      age (odds-ratio male/female=0.62, P=0.097) or age and other variables (odds
      ratio=0.71, P=0.17). At the end of the follow-up (up to 12 years), survival rates
      for the whole population were 59.6% and 54.4% for men and women, respectively
      (chi-square=1.4, P=0.24); excluding in-hospital deaths, the rates were 65.1% and
      64.8%, respectively (chi-square=0.21, P=0.65). CONCLUSIONS: In the short-term
      follow-up, women have a significantly higher mortality relative to men in an
      unadjusted analysis. This difference became non-significant after adjusting for
      age, or age and other variables. In the long-term follow-up, sex was not
      correlated with prognosis.

PMID- 14664776
TI  - Prospective study of job insecurity and coronary heart disease in US women.
AB  - PURPOSE: To examine prospectively the relationship between job insecurity and
      incidence of coronary heart disease (CHD) among women. METHODS: We conducted the
      study in 36,910 women from the Nurses' Health Study, a prospective cohort of
      female registered nurses residing in 11 US states. These women were 46 to 71
      years old, and did not have diagnosed CHD, stroke, or cancer at baseline (1992).
      We collected information on job insecurity in 1992 and coronary heart disease
      incidence between baseline (June 1, 1992) and return of the 1996 questionnaire.
      RESULTS: During 4 years of follow-up, we documented 154 incident cases of CHD
      (113 non-fatal cases of myocardial infarction (MI) and 41 CHD deaths). After
      adjustment for a wide array of potential confounders, the relative risk (RR) of
      total CHD over 2-year follow-up was 1.35 (95% CI, 0.78-2.34) and 1.04 (95% CI,
      0.69-1.57) over 4-year follow-up. Job insecurity appeared to significantly
      increase the risk of non-fatal MI in the short term (2-year follow-up: RR=1.89,
      95% CI, 1.03-3.50), though not over a longer follow-up period (RR=1.28, 95% CI,
      0.82-2.00), nor fatal CHD in the short term (RR=0.49, 95% CI, 0.22-2.08).
      CONCLUSIONS: These data suggest that job insecurity may increase the short-term
      risk of non-fatal MI in women.

PMID- 14664777
TI  - Invasive disease caused by Haemophilus influenzae: the sensitivity of statutory
      reporting.
AB  - PURPOSE: The objective of the study was to investigate the sensitivity of the
      statutory reporting of Haemophilus influenzae invasive disease (HIID) during the
      period between 1996 and 1997 in Catalonia, Spain. METHODS: The incidence of HIID
      reported passively by clinicians was compared with the cases detected by a system
      of microbiological surveillance. In all cases isolated, the age of the patient,
      the clinical form and the serotype were investigated. RESULTS: Sixty-six cases
      were passively reported and 111 were detected by microbiological surveillance.
      Overall sensitivity of reporting was 59.5% (95% CI, 50.7-69.1), with differences
      being observed according to the variables studied. The highest values were
      obtained in children under 5 years (87.8%; 95% CI, 73.7-95.9), in cases with
      meningitis and/or sepsis (64.3%; 95% CI, 50.4-76.6) and in serotype b (73.0%; 95%
      CI, 60.3-83.4). In the logistical regression analysis, only age under 5 years was
      associated with greater reporting (OR= 9.8; 95% CI, 2.5-37.8). CONCLUSIONS:
      Reported morbidity in children under 5 years is a good estimate of the true
      incidence of HIID in Catalonia (underreporting was 12.2%), but not for those
      above this age in whom the underreporting was 57.2%.

PMID- 14664778
TI  - Ethnicity, but not cancer family history, is related to response to a population
      based mailed questionnaire.
AB  - PURPOSE: To determine if family history and ethnic background are factors
      affecting response to a mailed cancer family history questionnaire from the
      Ontario Familial Breast Cancer Registry. METHODS: Individuals diagnosed with
      primary invasive breast carcinomas (probands) were mailed a family history
      questionnaire, the first contact in a multi-stage process. This questionnaire
      obtained cancer family history and ethnicity data. After one month, a follow up
      telephone call was made to those who did not return this questionnaire and
      attempts were made to ask similar questions by telephone interview.
      Characteristics of those responding to the mailed questionnaire were compared to
      those who responded to the telephone interview only. RESULTS: 339 probands were
      included in this study: 242 returned a mailed version of the questionnaire; 57
      completed the questionnaire over the phone. Cancer family history/genetic risk
      criteria was not significantly related to type of response. Probands identifying
      themselves as visible minorities were significantly less likely to respond to the
      mailed questionnaire than the telephone interview (11.6% vs. 22.8%, P=0.03).
      CONCLUSIONS: Having a family history of cancer did not appear to influence
      response to a mailed questionnaire, but those reporting an ethnic/racial
      background other than White were more likely to respond to a telephone interview.

PMID- 14664779
TI  - Etiology, antimicrobial susceptibility profiles, and mortality associated with
      bacterial meningitis among children in Egypt.
AB  - PURPOSE: Surveillance for patients with meningitis is a high priority in order to
      determine the etiology of disease and design prevention strategies. This study
      presents data on the causes of bacterial meningitis among children <6 years of
      age treated in a network of hospitals throughout Egypt. METHODS: Training was
      provided to standardize the collection of clinical information and optimize
      recovery of bacterial pathogens. Bacterial isolates were tested for antimicrobial
      resistance patterns using Kirby Bauer disk diffusion, E-test and/or Beta
      lactamase (BL) testing methods. RESULTS: Patients with culture-confirmed
      bacterial meningitis (228 children<6 years) were identified including 89 (39%)
      patients with H. influenzae (HI), 68 (30%) with Streptococcus pneumoniae (SP), 30
      (13%) with N. meningitidis (NM), 18 (8%) with Mycobacterium tuberculosis (MTB)
      and 23 (10%) with other bacteria. The overall case fatality ratio was high (24%)
      and increased among children with TB meningitis (56%). The susceptibility for HI
      to ampicillin (AMP), chloramphenicol (C) and ceftriaxone (CRO) was 21%, 13%, and
      100% respectively. The susceptibility for SP to C and CRO was 79% and 100%,
      respectively. CONCLUSIONS: HI and SP are the leading causes of bacterial
      meningitis among children in Egypt. The majority of HI strains tested were
      resistant to AMP or C suggesting the need for routine use of CRO as first line
      therapy. Among older children TB emerges as a significant cause of bacterial
      meningitis in Egypt.

PMID- 14664780
TI  - The role of clinical risk factors in understanding self-rated health.
AB  - PURPOSE: This study examines the importance of clinical risk factors for
      predicting self-ratings of general health status, with and without controls for a
      broad range of self-reported indicators of physical and psychological well-being.
      METHODS: Ordered probit models, estimated on 928 respondents aged 54 years and
      older who participated in an ongoing national survey in Taiwan, are used to
      examine the correlates of self-rated health. The model is estimated in two
      stages, first testing the association between clinical risk factors and self
      rated health and second, examining whether those clinical measures remain
      significant after controlling for a large number of other factors hypothesized to
      affect self-ratings. RESULTS: Most of the clinical variables are significantly
      associated with self-rated health, even in the presence of control variables. The
      largest effects pertain to the BMI, ratio of total to HDL cholesterol (among men)
      and presence of the epsilon4 allele of the APOE gene (among women). CONCLUSIONS:
      The results suggest a variety of pathways linking clinical measures to the self
      ratings. The findings also suggest that the clinical measures are less powerful
      predictors than self-reports about diverse aspects of well-being.

PMID- 14664781
TI  - Self-esteem and mortality: prospective evidence from a population-based study.
AB  - PURPOSE: Self-esteem is considered to be importantly associated with both
      psychosocial states such as depression as well as physical health. There are no
      population-based studies that examine the association between self-esteem and
      mortality. The objective of this study was to assess whether low self-esteem was
      prospectively associated with increased risk of death in a population-based
      sample of Finnish men. METHODS: A sample of 2682 male residents of Kuopio,
      Finland were interviewed and followed prospectively as part of the Kuopio
      Ischemic Heart Disease Risk Factor Study (KIHD). Characteristics of the KIHD
      sample at baseline included self-esteem, measured by the Rosenberg ten-item
      scale, socioeconomic factors, behavioral risk factors, other psychosocial
      characteristics, and prevalent diseases. Mortality was ascertained through
      linkage to the Finnish national death registry. We assessed the relationship
      between self-esteem and all-cause mortality using Cox proportional hazards
      models. RESULTS: Low self-esteem was associated with a two-fold [hazard ratio
      (HR)=2.0, 95% confidence interval (CI)=1.3-3.2] increase in age-adjusted
      mortality. This relationship was partially explained by behavioral and
      socioeconomic factors, and prevalent diseases, and fully explained by other
      psychosocial characteristics (hopelessness, depression, cynical hostility, and
      sullenness). When adjusted for hopelessness alone there was no increased risk
      associated with low self-esteem (HR=1.3, 95% CI=0.8-2.2). CONCLUSIONS: This study
      found no association between self-esteem and all-cause mortality after adjustment
      for other psychosocial characteristics, primarily hopelessness. Our understanding
      of the observed relationships between some psychosocial factors and mortality may
      be improved by simultaneous measurement of multiple psychosocial domains, thus
      diminishing the potential for residual confounding.

PMID- 14664782
TI  - Factors impacting questionnaire response in a Dutch retrospective cohort study.
AB  - PURPOSE: To study questionnaire length, type of consent, approach to recruitment,
      and subject characteristics on participation in epidemiologic studies. METHODS:
      As part of a health survey among Dutch subjects treated for ear, nose, and throat
      disorders in childhood, we conducted a pilot study of 200 individuals who were
      randomly assigned to one of four categories, defined by length of questionnaire
      (long vs. short) and type of consent form (basic vs. multi-option). In addition,
      among 8402 subjects eligible to be in the main study (average age 41 years in
      1997), we examined the effect of approach to recruitment and subject
      characteristics on participation rates. RESULTS: The pilot study showed a non
      significant 10% increase in participation rate using the shorter questionnaire,
      but no differences by type of consent form. In the full survey, the participation
      rate was 49% after the first mailing. Response increased by 15% after a written
      reminder and by 10% after a telephone survey. The total participation rate was
      74%. Attained age, sex, exposure status, age at exposure, and response to an
      earlier survey were determinants of participation rates. Among male non
      participants, outright refusal was less frequent than non-response. The refusal
      rate, unlike the non-response rate, was positively associated with older age at
      time of survey. CONCLUSIONS: Health survey participation is influenced by
      questionnaire length, frequency of contact, and subject characteristics.

PMID- 14664784
TI  - Regarding "An unexpected distribution of sodium concentration in serum specimens
      stored for more than 30 years".

PMID- 14664783
TI  - Pandemic influenza planning: using the U.S. Centers for Disease Control FluAid
      Software for small area estimation in the Canadian context.
AB  - PURPOSE: The U.S. Centers for Disease Control and Prevention (CDC) developed
      software (FluAid 2.0) to provide estimates of pandemic impact (deaths,
      hospitalizations, and outpatient visits). We wished to develop inputs for
      Alberta, Canada to use in place of program default values. We also wished to
      examine how FluAid output could be better contextualized for local users.
      METHODS: We developed distributions for age and age-sex specific proportions of
      population in groups at high risk of influenza complications for Alberta, Canada.
      In addition, we developed interpandemic influenza rates for Alberta, Canada. We
      used FluAid with this local data to obtain estimations of both pandemic and
      interpandemic impacts of influenza. The ratio of these impacts presents a context
      for understanding the FluAid outputs. RESULTS: There were differences in both the
      pattern and the magnitude of the Alberta rates from the FluAid defaults. For a
      pandemic estimate at a 25% attack rate (most likely) compared to an interpandemic
      year, the pandemic would result in 3.7 times as many outpatient visits, 3.9 times
      as many hospitalizations and 8.2 times as many deaths. CONCLUSIONS: We recommend
      that health service planners who use FluAid develop estimates for interpandemic
      influenza to provide crucial contextual information for pandemic planning.

PMID- 14664787
TI  - A new peptide ligand that targets particles and heterologous proteins to
      hepatocytes in vivo.

PMID- 14664788
TI  - In vivo PET imaging of gene expression in Parkinsonian monkeys.

PMID- 14664789
TI  - Ex vivo gene therapy using bone marrow-derived cells: combined effects of
      intracerebral and intravenous transplantation in a mouse model of Niemann-Pick
      disease.
AB  - Normal murine bone marrow cells were transduced with a retroviral vector to
      overexpress and release human acid sphingomyelinase (ASM). The transduced cells
      were then transplanted intravenously into 3-day-old, irradiated ASM-deficient
      mice, a model of human Niemann-Pick disease (NPD). At 4 weeks, engrafted mice
      received intracerebral injections of mesenchymal stem cells obtained from the
      original, transduced bone marrow. By 16 weeks, most of the treated NPD mice had
      near-normal levels of ASM activity in their tissues, including the brain;
      dramatically improved histology; and marked reductions in sphingomyelin.
      Cerebellar function also was normal, and the number of Purkinje cells was > 80%
      of normal. Remarkably, in certain regions of the cerebellum many of the surviving
      Purkinje cells expressed human ASM RNA, suggesting that either they were donor
      derived or that the transplanted bone marrow cells had fused with existing
      Purkinje cells. However, despite these positive results, by 24 weeks the ASM
      activities were dramatically reduced and cerebellar function began to decline,
      coincident with the detection of anti-human ASM antibodies in the plasma. We
      conclude that this gene therapy procedure might be useful in Type A NPD and other
      neurological lysosomal storage disorders, particularly since it is an approach
      that could be beneficial for both the neurological and the visceral organ
      features of these diseases.

PMID- 14664790
TI  - Effect of intranasal administration of Semliki Forest virus recombinant particles
      expressing reporter and cytokine genes on the progression of experimental
      autoimmune encephalomyelitis.
AB  - We have initiated studies to determine the feasibility of employing the Semliki
      Forest virus (SFV) expression system as a central nervous system (CNS) vector. We
      investigated the effects of infecting Balb/c mice intranasally (i.n.) with
      recombinant SFV particles expressing the enhanced green fluorescent protein
      (EGFP) reporter gene. EGFP expression was detected by fluorescence microscopy in
      the olfactory bulb as early as 1 day postinfection. No pathological changes were
      associated with infection. Viral RNA could be detected in the olfactory mucosa
      only, whereas fluorescence was detected in axons in the olfactory bulb,
      indicating that only the expressed protein was present. A vector expressing
      interleukin 10 (IL-10) was constructed and shown to induce good cytokine
      expression in cultured cells. IL-10 expression in the nasal passage and olfactory
      bulb of infected mice was enhanced following i.n. administration of such
      particles. Mice induced for experimental autoimmune encephalomyelitis (EAE) were
      treated i.n. with vectors expressing EGFP and IL-10 and with empty vector. The
      EGFP-expressing and empty vectors were found to exacerbate EAE, whereas that
      expressing IL-10 ameliorated EAE. It is concluded that the mice showed a
      significant biological response when treated i.n. with recombinant SFV particles
      and that such particles administered by the i.n. route have potential as a
      noninvasive vector for protein delivery to the CNS.

PMID- 14664791
TI  - Persistent phenotypic correction of central diabetes insipidus using adeno
      associated virus vector expressing arginine-vasopressin in Brattleboro rats.
AB  - Adeno-associated virus (AAV) vector is suitable for gene transfer to the central
      nervous system. However, the efficacy of gene therapy for neuroendocrine disease
      is still unknown. In this study, we injected AAV vector encoding arginine
      vasopressin (AVP) stereotaxically into the bilateral hypothalamus of Brattleboro
      rats. Brattleboro rats show a central diabetes insipidus (CDI) phenotype and
      growth retardation due to a complete deficiency of AVP. Following injection, both
      urine volume and urine osmolality normalized, and these therapeutic effects
      persisted for more than 50 weeks. In addition to phenotypic correction, secretion
      of transgene-derived AVP was enhanced after 24 h water deprivation or hypertonic
      saline injection, and water diuresis was demonstrated after acute water loading.
      Also, reduced body weight and low plasma insulin-like growth factor I levels of
      Brattleboro rats were restored after AVP gene transduction, suggesting the
      importance of AVP in growth. These findings indicate that hypothalamic neurons of
      Brattleboro rats can produce and release mature AVP following AAV-mediated gene
      transduction, resulting in long-term phenotypic correction of CDI. Moreover, the
      fact that transgene-derived AVP was secreted adequately in response to stimuli,
      even if it was expressed constitutively, suggests advantages of gene therapy for
      neuroendocrine diseases and offers a basis to investigate AVP function.

PMID- 14664792
TI  - Adeno-associated virus-mediated gene transfer of a secreted decoy human
      macrophage scavenger receptor reduces atherosclerotic lesion formation in LDL
      receptor knockout mice.
AB  - Macrophage scavenger receptors (MSR) promote atherosclerotic lesion formation,
      and modulation of MSR activity has been shown to influence atherosclerosis.
      Soluble receptors are effective in inhibiting receptor-mediated functions in
      various diseases. We have generated a secreted macrophage scavenger receptor
      (sMSR) that consists of the bovine growth hormone signal sequence and the human
      MSR A I extracellular domains. sMSR reduces degradation of atherogenic modified
      low-density lipoproteins and monocyte/macrophage adhesion on endothelial cells in
      vitro. To test long-term effects of sMSR, atherosclerosis-susceptible LDLR
      knockout mice were transduced via the tail vein with an adeno-associated virus
      (AAV) expressing sMSR or control enhanced green fluorescent protein (EGFP), and a
      Western-type diet was started. Gene transfer caused a temporary elevation in
      alkaline phosphatase and aspartate amino transferase values without a change in C
      reactive protein. sMSR protein was detected in the plasma of the transduced mice
      by a specific ELISA 6 months after the gene transfer. AAV-mediated sMSR gene
      transfer reduced atherosclerotic lesion area in the aorta by 21% (P < 0.05)
      compared to EGFP-transduced control mice. Even though eradication of established
      disease was not possible, atherosclerotic lesion formation could be modified
      using AAV-mediated gene transfer of the decoy sMSR.

PMID- 14664793
TI  - Self-complementary adeno-associated virus serotype 2 vector: global distribution
      and broad dispersion of AAV-mediated transgene expression in mouse brain.
AB  - The blood-brain barrier is the main obstacle to efficient delivery of therapeutic
      reagents, including viral vectors, into the central nervous system (CNS) for
      treating global CNS diseases. In this study, the effects of mannitol infusions on
      global brain gene expression of a novel AAV vector were examined after
      intravenous (i.v.) or intracisternal injection. Initially, a self-complementary
      adeno-associated virus serotype 2 vector (scAAV) was compared to traditional
      single-stranded AAV2 vector for reporter gene expression in the brain of adult
      mice with or without pretreatment of an i.v. mannitol infusion. One to two months
      postinjection, analysis of vector-transduced green fluorescent protein (GFP)
      expression in the brain revealed that vector delivery to the CNS via i.v.
      injection required pretreatment with mannitol. This expression was observed only
      when scAAV vectors were used. Using these conditions, transgene expression was
      observed in various neurons and glial cells throughout the brain. The
      peripherally administered scAAV vectors also transduced the cells in multiple
      somatic tissues with efficient expression in liver (20-30% of hepatocytes), but
      was less efficient in other somatic tissues. Intracisternal injection of scAAV
      vector produced a broad and intense transgene expression in both neurons and
      glial cells in the CNS of injected mice ranging from the olfactory area to the
      brain stem and spinal cord. More than 50% of the Purkinje cells in the cerebellum
      expressed GFP. Intravenous infusion of mannitol before intracisternal injection
      of the scAAV vector enhanced the dispersion of the vector in the CNS. Further
      optimization of these steps combining peripheral and intracisternal scAAV gene
      delivery should facilitate the development of treatments for global CNS diseases,
      especially diseases involving both the somatic system and the CNS, such as
      lysosomal storage disorders.

PMID- 14664794
TI  - Successful transgene expression with serial doses of aerosolized rAAV2 vectors in
      rhesus macaques.
AB  - Bronchoscopic microspraying of recombinant adeno-associated viral (rAAV) vectors
      targets high doses of vector directly to pulmonary epithelium. Single-dose
      endobronchial gene therapy trials have been accomplished in cystic fibrosis
      patients; however, repeated dosing strategies are likely essential for lifetime
      correction. These studies address whether serial redosing with rAAV2 vectors
      results in an antiserotypic response and, furthermore, whether it triggers an
      inflammatory response prohibitive to transgene expression. Serial redosing of 9 x
      10(11) infectious units of aerosolized rAAV2 vectors to rhesus macaques resulted
      in successful gene transfer by quantitative PCR (1.43 x 10(9) copies/g tissue)
      and transgene expression. Additionally, confocal microscopy and
      immunohistochemical analysis demonstrated in situ expression localized to the
      pulmonary epithelium. Although serial redosing did induce a heightened anti
      neutralizing antibody response in sera, gene transfer prevailed with resultant
      expression. This study is the first to demonstrate successful gene transfer
      subsequent to repeated aerosolized doses of rAAV2 in immunocompetent nonhuman
      primates without associated inflammatory responses prohibitive to transgene
      expression.

PMID- 14664795
TI  - Transient increase in lung epithelial tight junction permeability: an additional
      mechanism for enhancement of lung transgene expression by perfluorochemical
      liquids.
AB  - Intratracheal instillation of perfluorochemical (PFC) liquids enhances lung
      epithelial transgene expression by improved vector propulsion throughout lung
      airways. We now demonstrate that PFC liquids also facilitate gene transfer by
      increasing transepithelial permeability. Apical application of PFC liquid to well
      differentiated human airway epithelial cells resulted in a transient decrease in
      transepithelial resistance peaking approximately 2 h after PFC liquid
      administration and returning to normal approximately 24 h later. The permeability
      change was sufficient to enhance access of apically applied 100-nm latex beads
      and adenoviral vectors to the basolateral side of the culture. Adenovirus
      mediated gene expression was concurrently enhanced. Following intratracheal
      instillation of PFC liquid into mouse lungs, tight junction permeability, as
      assessed by electron microscopic evaluation of lanthanum deposition, was
      increased with peak effect between 6 h and 1 day after instillation. Importantly,
      alveolar-capillary permeability remained unchanged with the treatment.
      Administration of PFC liquid 6 h or 1 day, but not 3 days, prior to instillation
      of a recombinant adenovirus vector enhanced gene expression comparable to that
      observed with concurrent administration of PFC liquid and vector. We conclude
      that transient increase in epithelial permeability after PFC liquid
      administration contributes to the enhancement of adenovirus vector-mediated gene
      expression in lung epithelium.

PMID- 14664796
TI  - Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA
      nanoparticles in vivo.
AB  - DNA can be compacted using polyethylene glycol-substituted poly-L-lysine into
      discrete unimolecular (with respect to DNA) nanoparticles with minor diameter <
      20 nm that are stable in normal saline for at least 23 months at 4 degrees C. We
      compared the activity of firefly luciferase in lungs of C57BL/6 mice that
      received 100 microg compacted plasmid in 25 microl saline (shown to be the
      optimal dose) via intratracheal or intranasal instillation with levels in animals
      given 100 microg naked plasmid or in untreated mice. Mice dosed with compacted
      DNA nanoparticles had peak activity of luciferase in lung at 2 days
      postinstillation, which declined in log-linear fashion with a half-life of 1.4
      days. Luciferase activity in animals dosed with naked DNA was 200-fold less.
      Addition of polyethylene glycol to the complex was necessary for efficient gene
      transfer and animals that received DNA compacted with unmodified poly-L-lysine
      did not exhibit luciferase activity above background. Immunohistochemical
      staining for bacterial beta-galactosidase 2 days after administration of a
      compacted lacZ expression plasmid (n = 8) revealed expression predominantly in
      the dependent portions of the right lungs of mice, in alveolar and airway
      epithelial cells, though macrophages and sometimes endothelial cells also were
      transfected. No staining for beta-galactosidase was observed in uninjected
      animals (n = 4) or those dosed with naked lacZ plasmid (n = 7). Tissue survey for
      transgene expression shows expression only in lung and trachea following
      intranasal administration. Stable compacted DNA nanoparticles transfer exogenous
      genes to airway epithelium and show promise for lung gene therapy.

PMID- 14664797
TI  - Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lung.
AB  - Nanoparticles containing DNA compacted with poly-l-lysine modified on an N
      terminal cysteine with polyethylene glycol can effectively transfect cells of the
      airway epithelium when applied by the luminal route. To evaluate the toxicity of
      these nanoparticles, we administered 10 and 100 microg DNA compacted into
      nanoparticles suspended in normal saline by the intranasal route to mice and
      determined the pulmonary and systemic responses to this challenge, compared to
      administration of saline alone, and in some experiments, compared to
      administration of naked DNA, Escherichia coli genomic DNA, or lipofectin
      complexed naked DNA. There was no systemic response to either dose of
      nanoparticles in serum chemistries, hematologic parameters, serum complement, IL
      6, or MIP-2 levels or in the activity, growth, and grooming of the mice.
      Nanoparticles containing 10 microg DNA induced responses comparable to saline in
      all measures, including BAL cell counts and differentials and cytokine levels and
      histology. However, mice dosed with 100 microg DNA in nanoparticles had modest
      increases in BAL neutrophils 48 and 72 h after dosing, modest increases in BAL IL
      6 and KC beginning 24 and 48 h, respectively, after dosing, and, on histology of
      the lung, a trace to 1+ mononuclear cell infiltrates about the pulmonary veins at
      48 h, which were markedly reduced by 10 days and gone by 28 days after dosing.
      BAL neutrophil and cytokine responses were no greater than those entrained by
      naked DNA for up to 24 h. However, compared to administration of only 10 microg
      E. coli genomic DNA, the response to compacted DNA was much less. A low dose of
      lipofectin-complexed DNA (5 microg DNA) induced the same response as 20-fold
      higher doses of DNA nanoparticles. These data indicate that DNA nanoparticles
      have no measurable toxic effect at a dose of 10 microg and a very modest effect,
      which is not limiting, at a dose of 100 microg, which gives maximal gene
      expression. This favorable toxicity profile encourages development of stabilized
      compacted DNA for airway administration.

PMID- 14664798
TI  - Deoxyribonuclease II is a lysosomal barrier to transfection.
AB  - DNA delivered in nonviral vectors or as naked DNA must overcome a number of
      extracellular and intracellular barriers to transfection. Since many vectors
      deliver DNA into cells by the endocytic route, DNA degradation by lysosomal
      nucleases has been proposed as a significant barrier to transfection, despite the
      fact that this has not yet been formally demonstrated to occur. To test this
      hypothesis, we have investigated the role of deoxyribonuclease II (DNase II), the
      primary acidic endonuclease active in the lysosome, in transfection. Two genetic
      systems were engineered in which mammalian cells either overexpressed DNase II or
      were knocked out for the enzyme. In both models, higher levels of DNase II
      correlated with decreased transfection efficiency by nonviral DNA delivery
      vectors. These data provide direct evidence implicating lysosomal DNase II as a
      barrier to transfection.

PMID- 14664799
TI  - Efficacy of targeted FasL in nasopharyngeal carcinoma.
AB  - We have successfully achieved selective gene expression in human nasopharyngeal
      carcinoma (NPC) by exploiting the presence of the Epstein-Barr virus (EBV),
      utilizing a transcriptional targeting strategy (J. H. Li et al., 2002, Cancer
      Res. 62: 171). Building on this platform, we have generated a novel DeltaE1
      adenoviral vector mediating the expression of a mutant noncleavable form of the
      FasL gene (HUGO-approved symbol TNFSF6) (ad5oriP.ncFasL). We observe that this
      therapy induces significant cytotoxicity in the EBV-positive NPC cell line C666
      1, mediated by the induction of caspase-dependent apoptosis. The addition of
      ionizing radiation therapy (RT) causes additional cytotoxicity. Ex vivo infection
      of C666-1 cells with adv.oriP.ncFasL completely prevents tumor formation in SCID
      mice followed for up to 100 days. The combination of intratumoral adv.oriP.ncFasL
      with RT causes regression of established nasopharyngeal xenograft tumors for 2
      weeks' duration. Systemic delivery of this targeted strategy achieves 50-fold
      higher gene expression in nasopharyngeal tumors than in normal organs.
      Intravenously injected adv.oriP.ncFasL results in mild perturbation of liver
      function that returns to normal 2 weeks after initial therapy. These results
      demonstrate the efficacy of our EBV-specific targeting strategy, which allows the
      potentially safe and effective utilization of a highly potent membrane-based
      apoptotic gene.

PMID- 14664800
TI  - Retrovirally transduced muscle-derived cells contribute to hematopoiesis at very
      low levels in the nonhuman primate model.
AB  - Recent studies have suggested a remarkable potential of adult stem cells from a
      variety of organs to give rise to cells of disparate organs, but evidence of such
      potential at a clonal level is lacking in most if not all studies to date. To
      assess directly the hematopoietic potential of muscle-derived cells in a relevant
      large animal, we initiated retroviral-tagging studies in the rhesus macaque to
      allow tracking at the clonal level by integration site analysis. Four rhesus
      macaques underwent transplantation with transduced muscle-derived cells after
      lethal irradiation followed by delayed infusion of an autologous hematopoietic
      graft. The first animal showed no evidence of hematopoietic recovery and, despite
      infusion of the backup hematopoietic graft, succumbed due to complications of
      prolonged cytopenias. In the remaining three animals, the overall contribution of
      retrovirally tagged muscle-derived cells toward hematopoiesis was exceedingly
      low. Retroviral integration site analysis among clonally derived muscle cells and
      bone marrow cells in vivo in one animal suggests a common source. These results
      demonstrate that harvesting disparate organs for cellular therapy is currently
      highly inefficient at best.

PMID- 14664801
TI  - Induction of transgene-specific immunological tolerance in myeloablated nonhuman
      primates using lentivirally transduced CD34+ progenitor cells.
AB  - Modeling human hematopoietic progenitor cell gene therapy in nonhuman primates
      allows long-term evaluation of safety, maintenance of gene expression, and
      potential immune response against transgene products. We transplanted autologous
      G-CSF/SCF-mobilized CD34+ cells transduced with lentiviral vectors expressing
      EGFP into myeloablated rhesus macaques. To date, more than 4 years
      posttransplantation, 0.5-8% EGFP expression is maintained in multiple cell
      lineages. The animals remain healthy with no evidence of hematopoietic
      abnormalities or malignancies. To assess immune functions, we actively immunized
      two of our transplanted animals with purified rEGFP proteins and CpG adjuvant and
      demonstrated stable levels of EGFP+ cell populations maintained for over 29
      months despite four active immunizations. We did not detect a persistent anti
      EGFP antibody response or anti-EGFP T cell response in these immunized animals.
      Immune response to an irrelevant antigen was normal. Taken together, our data
      provide formal support that transplantation of lentivirally transduced CD34+
      progenitor cells in myeloablated rhesus macaques induces specific immunological
      tolerance toward a foreign transgene.

PMID- 14664802
TI  - Needle-free topical electroporation improves gene expression from plasmids
      administered in porcine skin.
AB  - Electroporation has been shown to increase the potency of DNA vaccines that have
      demonstrated significant potential in mice. However, there is a need to develop
      noninvasive or minimally invasive vaccination methods. In pigs, in vivo gene
      expression was assessed to compare intradermal needle injection to a needle-free
      dermal BioJect as a means of delivery of plasmids. Each administration method was
      further tested with and without surface electroporation. Experiments with plasmid
      DNA encoding luciferase demonstrated that needle-free administration results in
      higher gene expression levels than needle injection. Electroporation enhanced
      gene expression for both intradermal delivery methods. Needle-free plasmid
      injection in combination with electroporation led to a more rapid induction of
      immune responses compared to other methods of plasmid administration. It was
      concluded that needle-free topical electroporation significantly enhances gene
      expression, possibly by improving cellular uptake of plasmid DNA.

PMID- 14664803
TI  - In vivo trans-splicing of 5' and 3' segments of pre-mRNA directed by
      corresponding DNA sequences delivered by gene transfer.
AB  - We have developed a new paradigm of in vivo gene transfer termed "segmental trans
      splicing" (STS), in which individual "donor" and "acceptor" DNA sequences,
      delivered in vitro or in vivo, generate pre-mRNAs with 5' and 3' splice signals,
      respectively, and complementary hybridization domains through which the two pre
      mRNAs interact, facilitating trans-splicing of the two mRNA fragments. To
      demonstrate STS, we used alpha-cobratoxin, a neurotoxin that binds irreversibly
      to postsynaptic nicotinic acetylcholine receptors. Cells or animals receiving
      both donor and acceptor plasmids, but neither plasmid alone, yielded RT-PCR
      products with the correct sequence of mature alpha-cobratoxin mRNA, suggesting
      that trans-splicing had occurred. Mice receiving intravenous administration of >
      or = 7.5 microg donor + acceptor plasmids, but not either plasmid alone, died
      within 6 h. These data demonstrate that segmental trans-splicing occurs in vivo.
      This approach should permit the intracellular assembly of molecules hitherto too
      large to be accommodated within current gene transfer vectors.

PMID- 14664804
TI  - Detection of replication-competent adenoviruses spiked into recombinant
      adenovirus vector products by infectivity PCR.
AB  - The presence of replication-competent adenovirus (RCA) in clinical lots of
      adenovirus vectors raises a variety of safety concerns. To detect RCA in
      adenovirus vector products, the cell culture/cytopathic effect (CPE) method has
      generally been preferred. However, it is difficult to evaluate the amount of RCA
      clearly and quantitatively by this method. In addition, the cell culture/CPE
      method requires large-scale cell culturing and a substantial amount of time. For
      the purpose of establishing a method to detect RCA more sensitively and rapidly,
      we developed the infectivity PCR, a hybrid method that combines the infectivity
      assay and quantitative PCR. This method allows RCA to be quantified by real-time
      quantitative PCR using primers and a probe designed for E1 DNA. By infectivity
      PCR, 1 pfu of RCA spiked into 10(9) particles of adenovirus vectors could be
      detected. In contrast, CPE was observed in the cells infected with 10(4) pfu of
      RCA spiked into 10(9) particles of adenovirus vectors. The glass-beads method was
      suitable for extracting DNA rapidly from the RCA-infected cells. These results
      showed that infectivity PCR combined with the glass-beads-based DNA extraction
      method was useful for the detection of RCA in adenovirus vector products.

PMID- 14664805
TI  - Dynorphin A inhibits NMDA receptors through a pH-dependent mechanism.
AB  - Dynorphin A (DynA), an endogenous agonist of kappa-opioid receptors, has also
      been reported to directly interact with the NMDA receptor. DynA inhibition of
      NMDA receptor function has been suggested to be involved in its neuroprotective
      action during ischemic and acidic conditions. However, the effect of external pH
      on DynA inhibition of the NMDA receptor has not been reported. Here, we show that
      DynA inhibition of the NMDA receptor is dependent on extracellular pH over the
      range of pH 6.7-8.3, and the inhibition by 10 microM DynA increases at low pH by
      three- to four-fold in hippocampal neurons and in Xenopus oocytes expressing NR1
      1a/2B subunits. Molecular studies showed that the interacting site for DynA on
      the NMDA receptor is distinct from that of proton or redox sites. Peptide mapping
      demonstrated important contributions of positively charged residues and specific
      structural organization of the peptide to the potency of DynA inhibition. Thus,
      DynA inhibits NMDA receptors through an allosteric mechanism, which is pH
      dependent and involves the specific structural features of the peptide.

PMID- 14664807
TI  - Differential gene expression profiles in embryonic, adult-injured and adult
      uninjured rat spinal cords.
AB  - To identify genes that render the adult-injured spinal cord nonpermissive and the
      embryonic spinal cord permissive to regeneration, we used subtraction
      hybridization and suppression PCR to generate subtractive cDNA populations
      representing (1) genes expressed in the embryonic but not in the adult-injured or
      uninjured spinal cords, (2) genes expressed in the adult-injured but not in the
      embryonic or adult-uninjured spinal cords, and (3) genes expressed in the
      embryonic and adult-injured spinal cords but not in the adult-uninjured spinal
      cord. Between 85 and 98% of the cDNAs identified are differentially represented
      in each population. Genes in each cDNA population were identified by microarray
      hybridization. Genes involved in inflammation, apoptosis, and neuroprotection
      were overrepresented in injured spinal cord cDNA, whereas genes involved in cell
      signaling and differentiation were overrepresented in the embryonic cDNA. This
      gene expression profiling suggests new hypotheses regarding the genes involved in
      inhibition and promotion of spinal cord regeneration.

PMID- 14664806
TI  - Regulation of cpg15 by signaling pathways that mediate synaptic plasticity.
AB  - Transcriptional activation is a key link between neuronal activity and long-term
      synaptic plasticity. Little is known about genes responding to this activation
      whose products directly effect functional and structural changes at the synapse.
      cpg15 is an activity-regulated gene encoding a membrane-bound ligand that
      regulates dendritic and axonal arbor growth and synaptic maturation. We report
      that cpg15 is an immediate-early gene induced by Ca(2+) influx through NMDA
      receptors and L-type voltage-sensitive calcium channels. Activity-dependent cpg15
      expression requires convergent activation of the CaM kinase and MAP kinase
      pathways. Although activation of PKA is not required for activity-dependent
      expression, cpg15 is induced by cAMP in active neurons. CREB binds the cpg15
      promoter in vivo and partially regulates its activity-dependent expression. cpg15
      is an effector gene that is a target for signal transduction pathways that
      mediate synaptic plasticity and thus may take part in an activity-regulated
      transcriptional program that directs long-term changes in synaptic connections.

PMID- 14664808
TI  - Neotrofin, a novel purine that induces NGF-dependent nociceptive nerve sprouting
      but not hyperalgesia in adult rat skin.
AB  - We report peripheral actions in rats of Neotrofin, a purine derivative of
      therapeutic interest. Systemic injections mimicked NGF in eliciting sprouting of
      nociceptive nerves without affecting their regeneration. The sprouting was
      prevented by anti-NGF treatment, implicating endogenous NGF. We detected no
      Neotrofin-induced increases in cutaneous NGF levels or in retrograde NGF
      transport. In contrast, both NGF and phosphorylation of trkA increased
      significantly in DRGs, with a marginal appearance of phosphorylated trkA in
      axons. We conclude that the DRG effects of Neotrofin are responsible for its
      induction of sprouting. Neotrofin also induced a striking phosphorylation of
      axonal erk 1 and 2, which was, however, unaffected by anti-NGF treatment. We
      suggest that this NGF-independent MAP kinase activation is involved in
      nonsprouting functions of Neotrofin such as neuroprotection. Unlike injected NGF,
      Neotrofin did not induce hyperalgesia, supporting its candidacy as a treatment
      for peripheral neuropathies like those induced by diabetes and anticancer
      chemotherapy.

PMID- 14664809
TI  - Two novel mammalian Nogo receptor homologs differentially expressed in the
      central and peripheral nervous systems.
AB  - The regenerative capacity of the adult mammalian central nervous system is
      restricted by the myelinating oligodendrocytes that form a nonpermissive
      environment for axonal growth. Currently only the Nogo receptor (NgR), in complex
      with p75(NTR) neurotrophin receptor is known to be involved in this inhibitory
      signalling in neurons. NgR is a common receptor for the three inhibitory myelin
      proteins Nogo-A, OMgp, and MAG. Here we describe two novel Nogo receptor gene
      homologs named NGRL2 and NGRL3 from human and mouse that, like NGR, encode
      putative leucine-rich repeat containing GPI-anchored proteins. We show by in situ
      hybridisation and by RT-PCR that NGRL mRNAs are predominantly expressed in the
      neurons of the embryonic and adult central and peripheral nervous systems, and
      that they together with NGR possess distinct and partially nonoverlapping
      expression patterns. We also show that all four members of the reticulon family,
      including Nogo-A, are widely expressed in the nervous system, and therefore are
      possible ligands for the NgRLs.

PMID- 14664810
TI  - Secretion of intrinsic cues controls repulsion of nociceptive neurons.
AB  - The longstanding question of how the pattern of skin sensory innervation arises
      led us to investigate the behavior of rat DRG sensory axonal outgrowth.
      Outgrowing neurites from NGF-stimulated DRGs placed in close vicinity
      demonstrated repulsive behavior in the form of turning responses. In contrast,
      NT3-dependent neurites intermingled, as did neurites cultured without collagen
      embedding. These observations raise the possibility that secretion and not
      contact repulsion is the dermatome-building mechanism of nociceptive territories.
      Further experiments with functional antibodies against known secreted guidance
      molecules had no blocking effect. Our data provide evidence that the segmented
      pattern of skin nociceptive sensory maps is supported by unknown intrinsic cues
      released from the sensory axons themselves.

PMID- 14664811
TI  - Transient calretinin expression defines early postmitotic step of neuronal
      differentiation in adult hippocampal neurogenesis of mice.
AB  - We here show that the early postmitotic stage of granule cell development during
      adult hippocampal neurogenesis is characterized by the transient expression of
      calretinin (CR). CR expression was detected as early as 1 day after labeling
      dividing cells with bromodeoxyuridine (BrdU), but not before. Staining for Ki-67
      confirmed that no CR-expressing cells were in cell cycle. Early after BrdU, CR
      colocalized with immature neuronal marker doublecortin; and later with persisting
      neuronal marker NeuN. BrdU/CR-labeled cells were negative for GABA and GABAA1
      receptor, but early on expressed granule cell marker Prox-1. After 6 weeks, no
      new neurons expressed CR, but all contained calbindin. Stimuli inducing adult
      neurogenesis have limited (enriched environment), strong (voluntary wheel
      running), and very strong effects on cell proliferation (kainate-induced
      seizures). In these models the induction of cell proliferation was paralleled by
      an increase of CR-positive cells, indicating the stimulus-dependent progression
      from cell division to a postmitotic stage.

PMID- 14664812
TI  - Expression of the H3 receptor in the developing CNS and brown fat suggests novel
      roles for histamine.
AB  - Histamine and histamine receptors have been implicated in signaling mechanisms in
      developmental processes in the brain and peripheral organs. Pharmacological
      studies have also implied that the histamine H(3) receptor, in addition to acting
      as a presynaptic auto- and heteroreceptor in the central nervous system, is
      active in peripheral tissues. We show that detectable histamine H(3)-receptor
      expression during development and in adult rat is restricted to specific areas of
      the brain and to adipocytes and the capillary network in brown adipose tissue.
      Histamine H(3)-receptor mRNA expression was not detected in other internal organs
      studied, or in spinal or sympathetic chain ganglia. These results support a
      histaminergic involvement in brain development through activation of the
      histamine H(3) receptor and indicate a possible novel involvement of the
      histamine H(3) receptor as a mediator of the effects of histamine in
      thermogenesis in brown adipose tissue.

PMID- 14664813
TI  - Effects of proinflammatory cytokines on the growth, fate, and motility of
      multipotential neural precursor cells.
AB  - We have recently shown that the inflammatory process during experimental allergic
      encephalomyelitis (EAE), the animal model of MS, attracts transplanted NPC
      migration into the inflamed white matter. Here we studied how the proinflammatory
      cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma)
      affect NPC growth, survival, differentiation, and migration. Newborn rat striatal
      NPCs were expanded in spheres as nestin+, PSA-NCAM+, NG2(-) cells, which
      differentiated into astrocytes, oligodendrocytes, and neurons. NPCs expressed
      receptors of TNFalpha and IFNgamma but not interleukin-1. TNFalpha and IFNgamma
      inhibited sphere cell proliferation, determined by [(3)H]thymidine and BrdU
      incorporation. IFNgamma increased apoptotic cell death (determined by TUNEL
      stains); this effect partially blocked by TNFalpha. Neither cytokine affected NPC
      lineage fate, determined by percentage of GFAP+, neurofilament+, and GalC+ cells
      after differentiation. TNFalpha and IFNgamma increased outward migration of cells
      from spheres in vitro. Thus, TNFalpha and IFNgamma, key players in MS and EAE,
      inhibit NPC proliferation and induce their migration.

PMID- 14664814
TI  - Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion
      cells.
AB  - Ephrin-As are repulsive axonal guidance cues that regulate retinotectal
      projection. EphA tyrosine kinases, which are the receptors of ephrin-As, activate
      signaling cascades leading to cytosckeleton reorganization. Here, we address the
      role of cyclin-dependent kinase (Cdk) 5 in Eph receptor signaling induced by
      ephrin-A5. Ephrin-A5 induced a cell morphological response in PC-3M cells that
      endogenously express Cdk5 and EphA2, a receptor for ephrin-A5. This response was
      augmented by the transfection of p35, which is a neuronal regulator of Cdk5.
      While the morphological response of native PC-3M cells was not affected by
      olomoucine, an inhibitor of Cdk, the response was inhibited in the p35
      transfected cells. In retinal ganglion cells, either olomoucine at 20 microM or Y
      27632 at 10 microM, an inhibitor of Rho-kinase/ROKalpha/ROCKII, showed maximum
      inhibitory effect against ephrin-A5 (10 microg/ml)-induced growth cone collapse.
      Combined application of olomoucine and Y-27632 further suppressed the ephrin-A5
      induced response. Ephrin-A5 evoked phosphorylation of Cdk5 at Tyr15 and tau, a
      substrate of Cdk5 in retinal growth cones. Recombinant herpes simplex virus
      expressing Cdk5 mutant (kinase-negative or Tyr15 to Ala) showed a dominant
      negative effect on the ephrin-A5-induced growth cone collapse. These findings
      demonstrate that both Cdk5 and the Rho kinase pathway independently contribute to
      the downstream of ephrin-A-induced signaling in retinal ganglion cells.

PMID- 14664815
TI  - BACE1 (beta-secretase) transgenic and knockout mice: identification of
      neurochemical deficits and behavioral changes.
AB  - BACE1 is a key enzyme in the generation of Abeta, the major component of senile
      plaques in the brains of Alzheimer's disease patients. We have generated
      transgenic mice expressing human BACE1 with the Cam Kinase II promoter driving
      neuronal-specific expression. The transgene contains the full-length coding
      sequence of human BACE1 preceding an internal ribosome entry site element
      followed by a LacZ reporter gene. These animals exhibit a bold, exploratory
      behavior and show elevated 5-hydroxytryptamine turnover. We have also generated a
      knockout mouse in which LacZ replaces the first exon of murine BACE1.
      Interestingly these animals show a contrasting behavior, being timid and less
      exploratory. Despite these clear differences both mouse lines are viable and
      fertile with no changes in morbidity. These results suggest an unexpected role
      for BACE1 in neurotransmission, perhaps through changes in amyloid precursor
      protein processing and Abeta levels.

PMID- 14664816
TI  - Fibroblast growth factor-2 gene delivery stimulates axon growth by adult retinal
      ganglion cells after acute optic nerve injury.
AB  - Basic fibroblast growth factor (or FGF-2) has been shown to be a potent
      stimulator of retinal ganglion cell (RGC) axonal growth during development. Here
      we investigated if FGF-2 upregulation in adult RGCs promoted axon regrowth in
      vivo after acute optic nerve injury. Recombinant adeno-associated virus (AAV) was
      used to deliver the FGF-2 gene to adult RGCs providing a sustained source of this
      neurotrophic factor. FGF-2 gene transfer led to a 10-fold increase in the number
      of axons that extended past 0.5 mm from the lesion site compared to control
      nerves. Detection of AAV-mediated FGF-2 protein in injured RGC axons correlated
      with growth into the distal optic nerve. The response to FGF-2 upregulation was
      supported by our finding that FGF receptor-1 (FGFR-1) and heparan sulfate (HS),
      known to be essential for FGF-2 signaling, were expressed by adult rat RGCs. FGF
      2 transgene expression led to only transient protection of injured RGCs. Thus the
      effect of this neurotrophic factor on axon extension could not be solely
      attributed to an increase in neuronal survival. Our data indicate that selective
      upregulation of FGF-2 in adult RGCs stimulates axon regrowth within the optic
      nerve, an environment that is highly inhibitory for regeneration. These results
      support the hypothesis that key factors involved in axon outgrowth during neural
      development may promote regeneration of adult injured neurons.

PMID- 14664817
TI  - Glycogen synthase kinase-3 and Axin function in a beta-catenin-independent
      pathway that regulates neurite outgrowth in neuroblastoma cells.
AB  - We have sought to determine the roles of beta-catenin and the Wnt signaling
      pathway in neurite outgrowth using a model cell system, the Neuro-2a
      neuroblastoma cell line. Activation of the Wnt signaling pathway disrupts a
      multiprotein complex that includes beta-catenin, Axin, and glycogen synthase
      kinase-3 (GSK-3), which would otherwise promote the phosphorylation and
      degradation of beta-catenin. Stabilized beta-catenin accumulates in the cytosol
      and in the nucleus; in the nucleus it binds to TCF family transcription factors,
      forming a bipartite transcriptional activator of Wnt target genes. These events
      can be mimicked by lithium (Li(+)), which inhibits GSK-3 activity. Both Li(+) and
      the GSK-3 inhibitor SB415286 induced neurite outgrowth of Neuro-2a cells. Li(+)
      induced neurite outgrowth did not require beta-catenin-/TCF-dependent
      transcription, and increasing levels of beta-catenin either by transfection or
      using Wnt-3A was not sufficient to induce neurite outgrowth. Interestingly, Axin,
      which is also a substrate for GSK-3, was destabilized by Li(+) and ectopic
      expression of Axin inhibited Li(+)-induced neurite outgrowth. Deletion analysis
      of Axin indicated that this inhibition required the GSK-3 binding site, but not
      the beta-catenin binding site. Our results suggest that a signaling pathway
      involving Axin and GSK-3, but not beta-catenin, regulates Li(+)-induced neurite
      outgrowth in Neuro-2a cells.

PMID- 14664818
TI  - Expression patterns of the RGS9-1 anchoring protein R9AP in the chicken and mouse
      suggest multiple roles in the nervous system.
AB  - In retinal photoreceptors, the duration of G protein signalling is tightly
      regulated by the GTPase-activating protein RGS9-1. RGS9-1 is anchored to the disk
      membranes of photoreceptor outer segments by association with the membrane
      spanning protein R9AP. Here we report the cloning of chicken R9AP from an inner
      ear cDNA library and the isolation of a murine R9AP cDNA from a retinal library.
      In the chicken, R9AP appears to be expressed in a variety of neuronal tissues,
      particularly in sensory cells including inner ear hair cells, photoreceptors, and
      dorsal root ganglion neurons. In the mouse, R9AP is detectable predominantly in
      photoreceptors, but it is also weakly expressed in other areas of the central
      nervous system. The expression of R9AP beyond photoreceptors led us to examine
      potential alternative roles for R9AP besides anchoring RGS9-1 and we found
      sequence homology and structural similarity of the protein with members of the
      SNARE protein family. Expression of chicken and mouse R9AP interfered with
      intracellular trafficking of an indicator protein in an in vitro assay,
      suggesting a more active role of the protein, possibly in targeting. GTPase
      activating proteins to specific membranous compartments.

PMID- 14664819
TI  - Wnt signalling inhibits neural differentiation of embryonic stem cells by
      controlling bone morphogenetic protein expression.
AB  - Wnt signalling plays an important role in both embryonic development and in
      tumourigenesis. Activation of the signalling cascade by wnt, but also mutations
      of the adenomatous polyposis coli (APC) protein and of the phosphorylation domain
      of beta-catenin, result in accumulation of active beta-catenin in the nucleus,
      where it binds to TCF/LEF transcription factors. We studied the effect of wnt
      signalling in embryonic stem cells by either inactivating APC or by introducing a
      dominant active form of beta-catenin. Both resulted in inhibition of neural
      differentiation in vitro and after brain grafting and in activation of downstream
      targets of wnt signalling, such as cyclins, c-myc, and bone morphogenetic
      proteins (BMP). Neural differentiation could be partially restored by the
      addition of the BMP antagonist noggin. This suggests a mechanism regulating the
      fate of differentiating embryonic stem cells.

PMID- 14664820
TI  - Axonal sorting of Kir3.3 defines a GABA-containing neuron in the CA3 region of
      rodent hippocampus.
AB  - Hippocampal interneurons comprise a heterogeneous group of locally acting
      GABAergic neurons. In addition to their variability in cotransmitter content and
      receptor profile, they express a variety of potassium channels that specify their
      individual properties. Here we describe a new type of large GABA-containing
      neuron in rodent hippocampus that is characterized by an axonal sorting of the
      potassium channel Kir3.3. The parent cell bodies of the Kir3.3-positive axons are
      located in CA3, as assessed by primary cultures derived from hippocampal
      subareas. At postnatal day 14 these neurons appear at the border between stratum
      oriens and stratum pyramidale of CA3, from where their axons pass through stratum
      pyramidale to join the mossy fiber tract. In adult hippocampus, high levels of
      Kir3.3 channel protein exist in axons that run with the mossy fiber tract. Kir3.3
      and the vesicular GABA transporter could be identified in subpopulations of large
      synaptic terminals that probably derive from Kir3.3 neurons. Axonal sorting of
      Kir3.3 appears to be typical of a group of large inhibitory neurons, including
      Purkinje cells and a novel type of interneuron in CA3. Kir3.3 neurons might
      modulate the activity of CA3 circuitries and consequently memory processing in
      the hippocampus.

PMID- 14664821
TI  - Distinct domains of the limbic system-associated membrane protein (LAMP) mediate
      discrete effects on neurite outgrowth.
AB  - The limbic system-associated membrane protein (LAMP) is a
      glycosylphosphatidylinositol-anchored glycoprotein with three immunoglobulin (Ig)
      domains that can either enhance or inhibit neurite outgrowth depending upon the
      neuronal population examined. In the present study, we investigate the domains
      responsible for these activities. Domain deletion revealed that the N-terminal
      IgI domain is necessary and sufficient for the neurite-promoting activity
      observed in hippocampal neurons. In contrast, inhibition of neurite outgrowth in
      SCG neurons, which is mediated by heterophilic interactions, requires full-length
      LAMP, although selective inhibition of the second Ig domain, but not the first or
      third domains, prevented the inhibitory effect. This indicates that the IgII
      domain of LAMP harbors the neurite-inhibiting activity, but only in the context
      of the full-length configuration. Covasphere-binding analyses demonstrate IgI/IgI
      interactions, but no interaction between IgII and any other domain, consistent
      with the biological activities that each domain mediates. The data suggest that
      LAMP may serve as a bifunctional guidance molecule, with distinct structural
      domains contributing to the promotion and inhibition of neurite outgrowth.

PMID- 14664822
TI  - Phenotypic and molecular identity of cells in the adult subventricular zone. in
      vivo and after expansion in vitro.
AB  - We have studied the molecular identity of adult mouse SVZ cells in situ, and
      after isolation and expansion as neurospheres in vitro. The gene and protein
      expression patterns of the adult cells have been compared to that of the cells
      from the lateral ganglionic eminence (LGE), their putative embryonic
      counterparts. The LGE gives rise to both striatal projection neurons and
      olfactory bulb interneurons via spatially and molecularly distinct progenitor
      populations present in the SVZ of the LGE. These two populations are thought to
      have a common origin in the GSH2 expressing cells of the embryonic LGE
      ventricular zone. We found that a significant number of cells in the adult SVZ,
      and in the in vitro expanded neurospheres, derived from the adult SVZ express
      GSH2. However, under normal conditions, GSH2-expressing cells in the adult SVZ
      and in the in vitro expanded neurospheres appear to specify only olfactory bulb
      progenitors and not striatal progenitors.

PMID- 14664823
TI  - Phospholipase A2 plays an important role in myelin breakdown and phagocytosis
      during Wallerian degeneration.
AB  - Phospholipase A(2) (PLA(2)) hydrolyzes phosphatidylcholine to
      lysophosphatidylcholine and arachidonic acid. The former can induce myelin
      breakdown and the latter, via eicosanoids, can stimulate inflammatory responses.
      Immunohistochemical analysis of secreted (sPLA(2)) and cytosolic (cPLA(2)) forms
      of the enzyme was assessed in the injured adult rat sciatic and optic nerves.
      sPLA(2) and cPLA(2) are expressed in the first 2 weeks in the injured sciatic
      nerve, which correlates with rapid Wallerian degeneration in peripheral nerves.
      In contrast, both forms of PLA(2) were not expressed in the optic nerve for the
      first 3 weeks after crush injury, which correlates with slow Wallerian
      degeneration in the central nervous system (CNS). In addition, PLA(2) is not
      expressed in the lesioned sciatic nerve of C57BL/Wld(s) mutant mice in which
      Wallerian degeneration is severely retarded. Blocking cPLA(2) in the transected
      sciatic nerve of C57BL/6 mice, which have a naturally occurring null mutation for
      the major from of sPLA(2), resulted in a marked slowing of myelin and axonal
      degradation and phagocytosis in the distal nerve segment. These results provide
      direct evidence of an important role for cPLA(2) in Wallerian degeneration.

PMID- 14664824
TI  - Calcium-myristoyl switch, subcellular localization, and calcium-dependent
      translocation of the neuronal calcium sensor protein VILIP-3, and comparison with
      VILIP-1 in hippocampal neurons.
AB  - Neuronal calcium sensor (NCS) proteins including the subfamily of visinin-like
      proteins (VILIPs) are involved in regulation of various signaling cascades. One
      molecular regulation mechanism is the calcium-myristoyl switch. VILIPs show a
      calcium-dependent membrane association in brain homogenates; however, differences
      in calcium-induced conformation changes and degree of membrane association are
      reported. Little is known about differences in the calcium-myristoyl switch in
      living cells leading to localization of VILIPs to distinct subcellular
      compartments. Therefore, we studied the calcium-dependent localization of green
      fluorescent protein (GFP)-tagged VILIP-3 in living cell lines and hippocampal
      neurons and compared it with that of GFP-VILIP-1. Interestingly, the observed
      fast and reversible calcium-myristoyl switch of VILIP-3-GFP and VILIP-1-GFP
      differed, e.g., in calcium-dependent translocation to Golgi membranes.
      Similarily, the calcium-dependent localization of endogenously expressed VILIP-3
      and -1 in dendrites differed. Thus, VILIPs co-expressed in the same neuron show
      clear differences in calcium-dependent localization which may allow neurons a
      highly selective response to various calcium stimuli.

PMID- 14664825
TI  - Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical
      cultures involves activation of multiple nicotinic acetylcholine receptor
      subtypes.
AB  - Activation of neuronal nicotinic acetylcholine receptors (nAChR) by nicotine has
      been suggested to protect neurons against a hypoxic insult. The objective of this
      study was to examine the nature of cell death induced by acute hypoxia in rat
      primary cortical cultures and the neuroprotective potential of nicotine in
      ameliorating these processes. Neuronal cell death induced by a 4-h exposure to
      hypoxia (0.1% O(2)) was apoptotic, as shown by TUNEL staining and assays
      monitoring DNA strand breaks and caspase-3/7 activity. The presence of nicotine
      (10 microM) during the hypoxic insult protected a subpopulation of susceptible
      neurones against DNA damage and apoptosis induced by oxygen deprivation. This
      protective effect of nicotine was prevented by a 30-min pre-incubation with
      either 100 nM alpha-bungarotoxin or 1 microM dihydro-beta-erythroidine, but not 1
      microM atropine, suggesting that activation of at least two subtypes of nAChR,
      alpha7 and beta2* nAChR, is involved in mediating nicotine neuroprotection.

PMID- 14664826
TI  - Expression and glycanation of the NG2 proteoglycan in developing, adult, and
      damaged peripheral nerve.
AB  - We have investigated expression of the axon growth-inhibitory proteoglycan NG2 in
      peripheral nerve. In the adult, NG2 was present on endoneurial and perineurial
      fibroblasts, but not on Schwann cells. At birth, peripheral nerve NG2 was heavily
      glycanated, but was much less so in the adult. In vitro, sciatic nerve
      fibroblasts also produced heavily glycanated NG2. After peripheral nerve injury
      in rats and humans, an accumulation of NG2-positive cells was observed at the
      injury site. In the rat, there was an increase in NG2 glycanation for at least 2
      weeks following injury. In mixed cultures of Schwann cells and peripheral nerve
      fibroblasts, the axons preferred to grow on the Schwann cells and seldom crossed
      onto the fibroblasts. Three-dimensional cultures of sciatic nerve fibroblasts
      were inhibitory to the growth of dorsal root ganglion axons. Inhibition of
      proteoglycan synthesis made the cells more permissive. NG2 may play a part in
      blocking axon regeneration through scar tissue in injured human peripheral nerve.

PMID- 14664827
TI  - Distinct elements of the peripheral myelin protein 22 (PMP22) promoter regulate
      expression in Schwann cells and sensory neurons.
AB  - Genetic disease mechanisms in the demyelinating peripheral neuropathies Charcot
      Marie-Tooth disease type 1A (CMTA) and hereditary neuropathy with liability to
      pressure palsies (HNPP) as well as transgenic animals with altered PMP22 gene
      dosage revealed that alterations in PMP22 gene expression have profound effects
      on the development and maintenance of peripheral nerves. Consequently, the
      regulation of PMP22 is a crucial aspect in understanding the function of this
      protein in health and disease. In this study, we dissected and analyzed different
      cis-acting elements in the 5'-flanking region of the Pmp22 gene in vivo. We found
      two separate elements that contribute to different aspects of Pmp22 expression.
      The first is located 5' distally to promoter 1 and is involved in gene regulation
      during late phases of myelination in development ["late myelination Schwann cell
      specific element" (LMSE)] and in remyelination after injury. The second element
      was identified upstream of promoter 2 and guides Pmp22 expression in sensory
      neurons. These results suggest that multiple distinct signaling pathways
      regulating Pmp22 expression in myelination as well as in neurons converge on
      distinct segments of the PMP22 promoter region. The underlying molecular
      mechanisms are likely to be crucially involved in the maintenance of the
      integrity of myelinated peripheral nerves.

PMID- 14664828
TI  - Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated
      excitatory transmission to the superficial spinal dorsal horn.
AB  - Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic
      EPSCs of short duration. However, in the presence of the GABA(A) receptor
      antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be
      observed following the initial, fast response. A-fiber-induced ERK activation is
      also facilitated in the presence of bicuculline. The frequency of miniature EPSCs
      and the amplitude of the monosynaptic A-fiber-evoked EPSCs are not affected by
      bicuculline or the GABA(A) receptor agonist muscimol, suggesting that GABA(A)
      receptors located on somatodendritic sites of excitatory interneurons are
      critical for this action. Bicuculline-enhanced polysynaptic EPSCs are completely
      eliminated by NMDA receptor antagonists APV and ketamine, as was the augmented
      ERK activation. This NMDA receptor-dependent phenomenon may contribute to
      bicuculline-induced allodynia or hyperalgesia, as well as the hypersensitivity
      observed in neuropathic pain patients.

PMID- 14664829
TI  - Insulin induces a novel form of postsynaptic mossy fiber long-term depression in
      the hippocampus.
AB  - The mechanisms of induction and the site of expression of long-term depression
      (LTD) at the hippocampal mossy fiber-CA3 synapses are not clear. Here, we show
      that a brief bath application of insulin induces a novel form of mossy fiber LTD.
      This insulin-LTD is (1) induced and expressed postsynaptically, (2) entirely
      independent of synaptic stimulation during insulin application, (3) involving a
      rise in postsynaptic [Ca(2+)](i) and L-type voltage-activated Ca(2+) channel
      activation, (4) mechanistically distinct from low-frequency stimulation-induced
      LTD, (5) dependent on phosphatidylinositol 3-kinase signaling, and (6) associated
      with a clathrin-mediated endocytotic removal of surface 3-hydroxy-5
      methylisoxazole-4-propionic acid receptors from the postsynaptic neurons.
      Moreover, insulin-LTD is specific to mossy fibers to CA3 pyramidal cell synapses,
      and is not present at associational commissural synapses. These findings not only
      support a postsynaptic locus of mossy fiber LTD, but also provide a further link
      between the AMPA receptor trafficking and the bidirectional expression of long
      term synaptic plasticity.

PMID- 14664830
TI  - P2X receptor-mediated excitatory synaptic currents in somatosensory cortex.
AB  - Fast P2X receptor-mediated excitatory postsynaptic current (EPSC) was found in
      pyramidal neurones of layer V of somatosensory cortex in slices acutely isolated
      from the brain of 17- to 22-day-old rats. The EPSCs were elicited by field
      electrical stimulation in the layer VI at 0.1 Hz in the presence of picrotoxin.
      When the glutamatergic EPSC was blocked by glutamate receptors inhibitors NBQX
      and D-AP5, a residual EPSC (rEPSC) was recorded from 85% of neurones tested. This
      rEPSC was not affected by blockers of nicotinic (hexamethonium) and serotonin
      (Y25130) receptors; however, it was reversibly inhibited by P2X receptors
      antagonists (NF023, NF279, and PPADS). An application of ATP (20 microM),
      beta,gamma-methylene ATP (25 microM), and alpha,beta-methylene ATP (20 microM) to
      acutely isolated pyramidal neurones of layer V evoked inward currents (30 to 400
      pA) in 75% of cells tested. We concluded that several subtypes of P2X
      purinoreceptors participate in synaptic transmission in neocortex.

PMID- 14664831
TI  - Microbial transformation products of benzoxazolinone and benzoxazinone
      allelochemicals--a review.
AB  - Cyclic hydroxamic acids and lactams are allelochemicals present in the common
      agricultural crops wheat, rye, and maize. The hydroxamic acids are mainly present
      in the plants as glucosides. Upon injury or insect attack or when exuded to the
      soil environment, the hydroxamic acids occur in their unstable agluconic form. In
      the first step in the transformation of hydroxamic acids, benzoxazolinones are
      formed spontaneously. It is necessary to elucidate the further microbial
      transformation of these compounds in the soil environment for a purposeful
      exploitation of the allelopathic properties of wheat, rye, and maize. In the
      present paper, the existing knowledge on microbial transformation products of
      benzoxazolin-2-one (BOA), 6-methoxy-benzoxazolin-2-one (MBOA), and 2-hydroxy-1,4
      benzoxazin-3-one (HBOA) was reviewed. Three main groups of transformation
      products were identified: aminophenoxazinones, malonamic acids, and acetamides.
      Future research needs concerning the transformation of these chemicals in soil
      are discussed, when their properties for suppressing weeds and soil-borne
      diseases are going to be exploited.

PMID- 14664832
TI  - Simple and sequential extractions of heavy metals from different sewage sludges.
AB  - The presence of heavy metals in the sludges produced in waste-water treatment
      plants restricts their use for agricultural purposes. This study looks at
      different types of sludges (aerobic, anaerobic, unstabilised and sludge from a
      waste stabilisation pond) and compares the distribution of the heavy metals they
      contain according to the treatment that they have undergone. Some agronomic
      parameters necessary for characterising a sludge as suitable for use as amendment
      were determined. The aim of this study is to compare the availability and the
      localisation of heavy metals in different sewage sludges using simple (water and
      DTPA) extraction and the BCR (Community Bureau of Reference) sequential
      extraction procedure. It was confirmed that the total concentration of heavy
      metals did not exceed the limits set out by European legislation and that the
      stabilisation treatment undergone by the sludges strongly influenced the heavy
      metal distribution and the phases to which they were associated and their
      bioavailability level. The DTPA extraction procedure is cheap and easy to perform
      and the obtained results are similar to those obtained with the sequential
      procedure.

PMID- 14664833
TI  - Genetic and DNA-methylation changes induced by potassium dichromate in Brassica
      napus L.
AB  - This study evaluated genetic and DNA methylation alteration induced by potassium
      dichromate in Brassica napus L. plants. Amplified fragment length polymorphism
      (AFLP) and selective amplification of polymorphic loci (SAMPL) tests revealed
      dose-related increases in sequence alterations in plantlets exposed to 10-200
      mg/l potassium dichromate. Individual plantlets exposed to chromium under similar
      conditions showed different AFLP and SAMPL DNA profiles. These observations
      suggest random DNA mutation in response to potassium dichromate and argue against
      preferential sites for mutation. DNA methylation changes in response to chromium
      treatment were also evaluated. Two complementary approaches were applied: (i)
      immunolabelling, using a monoclonal antibody against 5-methylcytosine; and (ii)
      methylation-sensitive amplified polymorphism (MSAP). Immunolabelling showed
      cytosine-hypermethylation in the Brassica napus L. genome when plants were
      treated with potassium dichromate. MSAP analysis showed extensive methylation
      changes in CCGG-sequences, with the net result being genome-wide
      hypermethylation. These results showed a clear DNA alteration in plants as a
      response to chromium exposure and the effect was dose-dependent. DNA polymorphism
      detected by different markers supports the effectiveness of the use of these
      tools for the investigation of environmental toxicology and for evaluating the
      concentration of pollutants by DNA analysis in plants.

PMID- 14664834
TI  - Content of aliphatic hydrocarbons in limpets as a new way for classification of
      species using artificial neural networks.
AB  - It is demonstrated that biological species like limpets can be classified
      according to their level of n-alkanes when artificial neural networks are
      applied. Marine intertidal and subtidal limpets of the Canary Islands (Spain),
      Patella piperata, Patella candei crenata and Patella ulyssiponensis aspera were
      selected as bioindicator organisms. Samples were collected at four stations on
      the coasts of Fuerteventura. Concentration of n-alkanes in the soft tissues of
      the limpets has been determined by gas chromatography. Data were treated with
      artificial neural networks (ANNs) and it was found that using suitable
      architecture of a supervised artificial neural network, the limpets can be
      successfully distinguished (classified) up to 98%.

PMID- 14664835
TI  - Influence of organic ligands on Cr desorption from hydroxy-Cr intercalated
      montmorillonite.
AB  - Retention of metals as hydroxy precipitates on mineral surfaces is an important
      process maintaining environmental quality. Hydroxy precipitates of Cr(III) are
      particularly important because appreciable mobilisation of intercalated,
      hydrolysed Cr from montmorillonite is currently thought to occur only via
      oxidative dissolution. The present study examines the potential of oxalate,
      tartrate, and citrate to desorb Cr from both hydroxy-Cr and hydroxy Al-Cr
      precipitates sorbed to montmorillonite. For all intercalated clays there was an
      initial very rapid dissolution, followed by a slow but sustained Cr release that
      more closely followed a parabolic rate law, the latter indicative of transport
      controlled dissolution. The initial rapid dissolution persisted longer for the
      pure Cr clay ( approximately 48 h) than for the coprecipitated Al-Cr clay (
      approximately 24 h). At the end of the 30 d reaction, however, most Cr remained
      sorbed to the montmorillonite in all systems. Citrate, for example, solubilised
      only approximately 10% of the total sorbed Cr from the pure Cr clays. Aluminum
      presence decreased Cr solubilisation rate due to Al accumulation at the polymer
      margins. Moreover, Al presence maintained the integrity of the intercalated
      polymers and prevented c-axis expansion beyond 1.4 nm, thus restricting the
      supply of organic ligand to the inter-layer region. Oxalate, tartrate, and
      citrate were shown to be effective chelators of sorbed Cr and these ligands may
      therefore play an important role in the mobilisation and cycling of this metal in
      soils and sediments.

PMID- 14664836
TI  - Photolytic clean-up of biological samples for gas chromatographic analysis of
      chlorinated paraffins.
AB  - A method based on gas chromatography electron capture detection (GC-ECD) for the
      analysis of chlorinated paraffins (CPs) in biological samples has been
      investigated. The method includes photolytic destruction of halogenated aromatic
      compounds, such as PCBs, to eliminate some of the interferences in the analysis
      of CPs in environmental samples. Gel permeation chromatography was used to
      isolate CPs from the interfering components of Toxaphene and chlordane after the
      photolysis. GC-ECD gave a detection limit of 20 ng CPs/g fresh muscle tissue. The
      recovery of CPs from a spiked moose liver sample was estimated to 94%.

PMID- 14664837
TI  - Quantitative determination of de-conjugated chrysene metabolites in fish bile by
      HPLC-fluorescence and GC--MS.
AB  - Two analytical methods have been evaluated for quantitative determination of de
      conjugated chrysene metabolites in fish bile. High performance liquid
      chromatography-fluorescence (HPLC-F) and gas chromatography-mass spectrometry (GC
      -MS) were compared regarding instrumental and overall limits of detection (LOD)
      as well as recoveries for the following nine chrysene compounds: 1-, 2,- 3-, 4-
      and 6-hydroxychrysene (1-, 2-, 3-, 4- and 6-OH-chr), 1,2-dihydroxy-1,2
      dihydrochrysene (1,2-DHD-chr), 3,4-dihydroxy-3,4-dihydrochrysene (3,4-DHD-chr),
      5,6-dihydroxy-5,6-dihydrochrysene (5,6-DHD-chr) and chrysene. Instrumental LODs
      were comparable for the two methods whereas the overall LOD was better for HPLC
      F. Recoveries varied per chrysene compound for both HPLC-F (62-107%) and GC-MS
      (48-124%). In vivo formed chrysene metabolites were studied in the bile of
      Atlantic cod (Gadus morhua) exposed to chrysene (1 mg/kg) via intra-peritoneal
      (i.p.) and inter-muscular (i.m.) injection. Total amounts of chrysene metabolites
      were three times higher in i.p. compared to i.m. exposed cod bile, but the
      relative distribution of determined metabolites was very similar. 1,2-DHD-chr was
      the most prominent metabolite in de-conjugated bile and constituted more than 88%
      of the total chrysene metabolites. Additional chrysene metabolites formed were
      3,4-DHD-chr and 1-, 2-, 3- and 4-OH-chr. K-region chrysene metabolites (oxidation
      at carbons 5 and 6) were not detected and seem to be a less favoured
      biotransformation route. The two methods were applied and evaluated for analysis
      of chrysene metabolites in two bile reference materials (BCR 720 and 721) and a
      limited number of field exposed cods.

PMID- 14664838
TI  - Enhancement of photocatalytic activity of sprayed nitrogen-containing ZnO powders
      by coupling with metal oxides during the acetaldehyde decomposition.
AB  - Colored N-containing MOx-ZnO (M = W, V) composite powders with high surface area
      were synthesized by spray pyrolysis. The nitrogen content was controlled from 600
      to 3000 ppm by changing the powder ingredients and the spray pyrolysis
      temperature. Ultraviolet-visible spectra indicated that the N-containing MOx-ZnO
      powders absorbed not only ultraviolet light like pure ZnO powder, but also some
      visible-light. Acetaldehyde decomposition was used as a probe reaction to
      evaluate the photocatalysis of these MOx-ZnO powders. The photocatalytic activity
      of the N-containing ZnO powder was pronouncedly enhanced by the WO3 or V2O5
      addition under both UV and visible-light irradiation. This enhancement was
      ascribed to the MOx acting as a sink for photogenerated electrons in the UV case,
      and to a synergistic effect of N-doping and MOx-ZnO coupling in the case of
      visible-light.

PMID- 14664839
TI  - Concentrations and specific loads of polycyclic musks in sewage sludge
      originating from a monitoring network in Switzerland.
AB  - Polycyclic musks (HHCB, AHTN, ADBI, AHDI, ATII) and a metabolite of HHCB (HHCB
      lactone) were analyzed in sewage sludge samples within the framework of a
      monitoring network in Switzerland. Mean values in stabilised sludge from 16
      wastewater treatment plants were 20.3 mg/kg d.m. for HHCB, 7.3 mg/kg d.m. for
      AHTN and 1.8 mg/kg d.m. for HHCB-lactone, respectively. Contents of ADBI, AHDI
      and ATII were between 0.1 and 1.8 g/kg d.m. The results show that polycyclic
      musks origin mainly from private households and that loads from craft industry,
      industry and atmospheric deposition are negligible. The technology of wastewater
      treatment and sludge processing seems to be of minor importance for degradation
      processes of polycyclic musks. The calculated input in wastewater of polycyclic
      musks is lower by a factor of 5-7 than the estimates based on use volumes. This
      discrepancy might be explained by degradation processes, other emission pathways
      than wastewater or inappropriate estimation of production volumes.

PMID- 14664840
TI  - Time of flight secondary ion mass spectrometry studies of the distribution of
      metals between the soil, rhizosphere and roots of Populus tremuloides Minchx
      growing in forest soil.
AB  - Time of flight secondary ion mass spectroscopy has been used to study the metal
      distribution at the soil/root interface of tree roots extracted from smelter
      impacted soils. The results, augmented by scanning electron microscopy, show that
      the technique is capable of resolving metal distributions at the cellular level.
      In addition, the distribution of metals between the root plaque and the root
      interior may be useful in interpreting local metal transport mechanisms.

PMID- 14664842
TI  - Prognosis of environmental concentrations by geo-referenced and generic models: a
      comparison of GREAT-ER and EUSES exposure simulations for some consumer-product
      ingredients in the Itter.
AB  - The aim of this study was the comparison between predicted environmental
      concentrations (PEC) derived using a generic aspacial model, European Union
      System for the Evaluation of Substances (EUSES), and a geo-referenced model, the
      Geo-referenced Regional Environmental Assessment Tool for European Rivers (GREAT
      ER). The PECs of some consumer-product ingredients (boron, LAS) and professional
      uses (EDTA, NTA and Triclosan) were calculated for the river catchment of the
      Itter, a small tributary to the river Rhine. The PEClocal and PECregional for the
      water compartment generated by EUSES (default scenario) were subsequently refined
      with data that realistically reflects the region of North Rhine-Westphalia (NRW
      scenario) and the Itter catchment (Itter scenario). The results of the three
      scenarios were then compared with the PECinitial and PECcatchment calculated by
      GREAT-ER, that was designed as a higher-tiered exposure assessment tool, and with
      concrete concentrations in the Itter, measured as 24-h composite samples. While
      the PECregional of all scenarios was close to the lower end of the measured
      concentrations, the geo-referenced PECs described equally well the real spacial
      situation. The measured environmental concentrations confirmed the built-in
      conservatism of the PEClocal calculations by EUSES showing for all investigated
      chemicals an unrealistically high PEClocal (default). The refinement in the more
      realistic scenarios could not provide a straight forward general improvement of
      the PEClocal. In conclusion, when the EUSES prognosis is refined using more
      detailed substance and regional specific data, it may provide a fairly accurate
      modelling especially of substances that are not eliminated in the environment.
      However, in the case of eliminable substances, it does not match the accuracy of
      higher-tiered geo-referenced exposure models like GREAT-ER.

PMID- 14664841
TI  - Variation in estrogenic activity among fractions of a commercial nonylphenol by
      high performance liquid chromatography.
AB  - Estrogenic activity by recombinant yeast screen assay of the commercial NP was
      considerably higher when compared with that of n-nonylphenol (n-NP).
      Fractionation of the commercial NP by high performance liquid chromatography
      (HPLC) afforded seven isomers: 4-(1,3-dimethyl-1-propyl-butyl)-phenol, 4-(1,1,3
      trimethyl-hexyl)-phenol, 4-(1,1-dimethyl-3-ethyl-pentyl)-phenol, 4-(1,1,4
      trimethyl-hexyl)-phenol, 4-(1-methyl-1-propyl-pentyl)-phenol, 4-(1,1,2-trimethyl
      hexyl)-phenol and 4-(1-ethyl-1-methyl-hexyl)-phenol. The structures of these
      isomers were determined by GC-MS and nuclear magnetic resonance spectroscopy
      (NMR). All of these isomers possessed tertiary alpha-carbon in their chemical
      structures. Another tertiary NP, 4-(1,1-dimethyl-heptyl)-phenol was synthesized
      in the present study and this synthetic NP also exhibited the estrogenic
      activity. One fractionated compound was identified as one of decylphenol, 4-(1
      ethyl-1,4,4-trimethyl-pentyl)-phenol. The isomer, 4-(1,1,4-trimethyl-hexyl)
      phenol exhibited the highest estrogenic activity corresponding to 1/10000 that of
      17beta-estradiol (E2). The activity of n-NP was the least. This suggests that it
      may be possible to develop a technical NP mixture with relatively low estrogenic
      activity.

PMID- 14664843
TI  - Environmental concentrations of boron, LAS, EDTA, NTA and Triclosan simulated
      with GREAT-ER in the river Itter.
AB  - A computer simulation of the environmental concentrations of some typical
      consumer-product ingredients was performed using the geo-referenced exposure
      model GREAT-ER (Geo-referenced Regional Environmental Assessment Tool for
      European Rivers) in the river Itter. Boron and LAS were chosen as typical
      detergent ingredients along with EDTA, NTA and Triclosan as examples of household
      and cosmetic product ingredients. The simulations were based on consumption
      figures of the respective chemical in consumer products in the year 2000. For
      EDTA, the consumption figure used for the calculation had to be extended to
      commercial products since the EDTA-use in domestic products could not account for
      the measured concentrations alone. The resulting PEC (Predicted Environmental
      Concentration) for all investigated compounds showed very good accordance to the
      measured concentrations in the Itter which were monitored in the same year. The
      concentrations did not deviate more than by a factor of 3. GREAT-ER's calculated
      90th-percentile was never exceeded by the monitoring result thus reflecting a
      reasonable accuracy.

PMID- 14664844
TI  - Persistence of carbofuran in marine sand and water.
AB  - Marine sand and seawater samples were collected in March 2002 from Laysan Island
      in the Hawaiian Islands National Wildlife Refuge, where a small area was
      contaminated by the carbamate insecticide carbofuran. Carbofuran was still
      detected at microg g(-1) levels in the Laysan sand after its identification in
      1998 and initial observation of the toxicity in 1988. The persistence of
      carbofuran in the marine sand was investigated in the dark in a 30 degrees C
      oven, and in distilled deionized water and seawater samples exposed to artificial
      300 nm light and to direct sunlight. The laboratory study showed a half-life
      (t1/2) of approximately 40 days for carbofuran in the native sand and in Ottawa
      sand. The photolysis of carbofuran was faster in seawater than in distilled
      deionized water when it was exposed to 300 nm light (t1/2, 0.1 vs. 3.1 h) and to
      direct sunlight (t1/2, 7.5 vs. 41.6 h). The large difference between the
      laboratory results and the field observation of carbofuran dissipation suggests
      that carbofuran degradation at the remote, undisturbed marine site may be
      governed by its unique environmental factors.

PMID- 14664845
TI  - Deacidification effect of the litter layer on forest soil during snowmelt runoff-
      laboratory experiment and its basic formularization for simulation modeling.
AB  - The forest soil ecosystem can buffer and neutralize acidic airborne pollutants to
      some extent, but extensive acidification degrades the soil ecosystem. Several
      investigations have shown that surface flows often show particularly low pH
      values in rivers and lakes during snowmelt and that this acidification phenomenon
      takes place in a short time frame. Acid water from snowmelt first makes contact
      with the litter layer in the soil ecosystem. Therefore, a laboratory experiment
      was performed to study the impact of forest litter on the chemical composition of
      the water solution. The experiment presented in this paper confirmed that
      deacidification with a little leachate of organic matter is caused by cation
      exchange not only in upper mineral soil but also in the litter layer and that
      leachate of labile Al is restrained in the presence of litter. An attempt was
      made to incorporate these factors into the biogeochemical module of the model
      (ILWAS) to accurately estimate damage by acidification.

PMID- 14664846
TI  - Characterization of chemical species in atmospheric aerosols in a metropolitan
      basin.
AB  - Ambient PM10 aerosol samples were collected from Taiwan's Taichung metropolitan
      basin between October 1997 and January 1998, and their chemical characteristics
      studied. The average mass concentration of PM10 was 109.0 +/- 54.1 microg/m3.
      Carbonaceous materials, sulfate, nitrate, and ammonium were the most important
      contributors to the PM10 component. On average, 64% of the PM10 was made up of
      fine particles. During PM10 episodes, average wind speed was 0.7 m/s and relative
      humidity was high, 83% on average, probably giving rise to stagnation of air
      pollutants and their entrapment close to the surface. With relative humidity <
      70%, NO3-, NH4+, SO4(2-), carbonaceous materials, and PM10 mass showed high
      correlation with maximum hourly average ozone (O3M). Variation in atmospheric
      humidity may affect the gas-to-particle interactions of S and N species. The most
      significant contribution to PM10 in the Taichung urban basin was from the
      photochemical formation of secondary aerosols and carbonaceous materials in the
      atmospheric environment.

PMID- 14664847
TI  - Influence of UV irradiation on the toxicity of phenylurea herbicides using
      Microtox test.
AB  - Halogenated phenylurea herbicides are not very toxic by themselves to animals,
      but their exposure to UV light may significantly increase the toxicity of their
      solutions. Absorption of light may indeed induce a phototransformation of the
      herbicide with a possible formation of more toxic intermediate photoproducts.
      Fortunately in environmental conditions photolysis is usually slow and
      photoproducts do not accumulate appreciably. Microtox was used for the evaluation
      of the toxicity of the crude irradiated solutions of some phenylurea herbicides.
      The sharp initial increase of toxicity shown by metobromuron solutions is mainly
      due to intermediate photoproducts which rapidly disappear. In the case of diuron
      and metoxuron toxicity is due to minor photoproducts and it does not disappear so
      rapidly. Hence the decrease of herbicide concentration is not necessarily
      associated to a lower toxicity of the solution.

PMID- 14664848
TI  - Supercritical fluid extraction of polycyclic aromatic hydrocarbons from marine
      sediments and soil samples.
AB  - Supercritical fluid extraction (SFE) was used to extract polycyclic aromatic
      hydrocarbons (PAH) from a certified sample of marine sediment. This sample
      contains a great number of organic pollutants that are present in low
      concentrations. The extractions were carried out at 50 and 80 degrees C, at a
      pressure varying from 230 to 600 bar and using CO2 in the supercritical phase and
      the effect of three organic modifiers (methanol, n-hexane and toluene), added at
      5%/vol, at the same temperature and pressure conditions, were then considered.
      PAHs were characterized by GC-MS and the recover yield was estimated for 6 PAHs
      that were representative of those present in the sample, according to their
      molecular weight and to the number of condensed rings. The analytical conditions
      giving the best recovery efficiency were used on an unpolluted soil sample spiked
      with 11 PAHs of environmental importance at a concentration similar to that
      certified for the sediment sample. An increase in the yield of recovered PAHs,
      using methanol as co-solvent, was observed while higher temperatures caused a
      negative effect on the quantity of recovered pollutants. The recovery yield for
      PAHs from the spiked soil sample was measured and found to be greater than 90%.
      Better recoveries were obtained for those compounds with higher molecular weight.

PMID- 14664849
TI  - Evaluation and standardisation of a simple HG-AAS method for rapid speciation of
      As(III) and As(V) in some contaminated groundwater samples of West Bengal, India.
AB  - A simple HG-AAS technique has been evaluated and standardised for rapid
      speciation of As(III) and As(V) in a number of contaminated groundwater samples
      of West Bengal, India. Citric acid has been used for selective hydride formation
      of As(III). The sensitivity of the evaluated HG-AAS method is 7.91 mg(-1)l,
      standard deviation, 0.001 and detection limit, 0.4 microg l(-1). As(III)
      sensitivity remains constant in the sample pH range of 2.3-10.6. Concomitant
      mineral matrix of the water samples did not interfere with arsenic determination.
      Eight out of ten groundwater samples analysed for As(IlI)and As(V) contain more
      As(III), which lies in the range of 54-350 ppb. As(III) estimation in drinking
      water along with total arsenic should be invoked as a policy for a realistic risk
      assessment of the contaminated water.

PMID- 14664850
TI  - Photochemical degradation of selected nitropolycyclic aromatic hydrocarbons in
      solution and adsorbed to solid particles.
AB  - To examine the relationship between the nitro group orientation and photochemical
      degradation, a series of NPAHs, including 6-nitrochrysene, 9-nitroanthracene and
      6-nitrobenzo(a)pyrene were irradiated both dissolved in CH3CN and adsorbed onto a
      surface (alumina, silica, carbon and cellulose). In solution, not all NPAHs
      displayed a relationship between their relative and nitro group orientation. In
      the adsorbed state, the nature of the particle appeared to have more of an
      influence than did the structure of the NPAH. If the compound degraded, the main
      product was generally a quinone.

PMID- 14664851
TI  - Purification of triolein for use in semipermeable membrane devices (SPMDs).
AB  - Analyses of triolein-containing semipermeable membrane devices (SPMDs) have
      sometimes been impeded by interferences caused by impurities endemic to triolein
      that codialyze with the analytes. Oleic acid and methyl oleate have been the most
      troublesome of these impurities because of their relatively high concentrations
      in triolein and because significant residues of both can persist even after size
      exclusion chromatographic (SEC) fractionation. These residues have also been
      blamed for false-positive signals during bioindicator testing of SPMD dialysates.
      To prevent these problems, a simple, cost-effective procedure was developed for
      purifying triolein destined for use in SPMDs: the bulk triolein is repeatedly
      (6x) partitioned against methanol. Tests of the procedure show that 14C-oleic
      acid is completely removed from the triolein. After SEC fractionation, dialysates
      of standard-size SPMDs made with the purified triolein contain less than 5 microg
      of methyl oleate as compared to sometimes more than 500 microg for dialysates
      (also after SEC) of SPMDs made with unpurified triolein. Gas chromatographic
      analyses with flame ionization and electron capture detection show that the
      purification treatment also greatly reduces the number and size of peaks caused
      by unidentified contaminants in the triolein. Microtox basic assay of dialysates
      of SPMDs shows that those made with the purified triolein have lower acute
      toxicities than dialysates of SPMDs made with unpurified triolein. Yeast estrogen
      screen (YES) testing of SPMDs fabricated with unpurified and purified triolein
      demonstrates that the purification process removes all background estrogenic
      activity.

PMID- 14664852
TI  - Comparison of toxicological impacts of integrated and chemical pest management in
      Mediterranean greenhouses.
AB  - The goal of this paper is to assess the relative impacts of pest-control methods
      in greenhouses, based on current LCA tools. As a case study, the relative impacts
      of two tomato production methods, chemical pest management (CPM) and integrated
      pest management (IPM), are assessed. The amount of the active ingredients
      applied, the fate of the ingredients in the various greenhouse and environmental
      compartments, the human exposure routes via the various compartments and the
      inherent toxicity of the ingredients were taken into account in the relative
      impact calculations. To assess the importance of model selection in the
      assessment, pesticide-specific fate and exposure factors for humans and aquatic
      and terrestrial ecosystems, used to aggregate pesticide emissions, were
      calculated with two different models: (1) the USES-LCA model, adapted in order to
      calculate the pesticide transfer from greenhouse air and soil to fruits, and (2)
      the empirical model critical surface time (CST). Impact scores have in general
      shown a higher level of potential contamination in greenhouses treated with CPM
      compared to IPM (a factor of 1.4 to 2.3). Relative impacts have been shown highly
      dependent on the selection of specific pesticides and crop stage development at
      the moment of pesticide application. This means that both CPM and IPM could be
      improved by a careful selection of pesticides. In order to improve the relative
      impact calculations, future research in pesticide transfer to food will be
      necessary.

PMID- 14664853
TI  - Humic acids from oxidized coals I. Elemental composition, titration curves, heavy
      metals in HA samples, nuclear magnetic resonance spectra of HAs and infrared
      spectroscopy.
AB  - The formation of humic acids (HAs) from bituminous coal was verified by
      laboratory oxidation. In a relatively short time the oxidation by air at
      temperature above 150 degrees C led to the formation of HAs. These HAs were
      compared with those isolated from oxidized bituminous coal from the vicinity of
      red bed bodies, from weathered bituminous coal, oxihumolite and lignite. For this
      the organic and inorganic elemental composition of HAs, apparent dissociation
      constants, metal-binding capacities, nuclear magnetic resonance and infrared
      spectra were determined and evaluated. With increasing temperature of laboratory
      oxidation of bituminous coal the percentage of aromaticity of HAs increases. HAs
      prepared from coal oxidized at 150 degrees C are characterized by an aromaticity
      index 78% while for HAs prepared at 250 and 300 degrees C by 95% aromaticity. The
      same index for HAs isolated from naturally oxidized bituminous coals is of about
      87% whereas it is of about 50% for oxihumolite and lignite. The apparent
      dissociation constants (Kapp) are much higher in HAs isolated from oxihumolite
      and lignite (pKapp from 3.35 to 3.80) than those from oxidized bituminous coal
      samples (pKapp from 4.47 to 4.85). There is a good negative correlation between
      Pb-binding capacity and pKapp of all samples suggesting that metallic ions are
      bonded to acidic groups of HAs. Also contents of inorganic elements like Fe, Al,
      Si are much higher in HAs isolated from lignite and oxihumolite than those in HAs
      from oxidized bituminous coal. Thus, it seems that the temperatures below 150
      degrees C and the long oxidation time are necessary conditions for the formation
      of HAs in oxidative altered bituminous coal deposited deeply under the earth
      surface.

PMID- 14664854
TI  - Level and distribution of DDT in surface soils from Tianjin, China.
AB  - One hundred and eighty eight surface soil samples were collected from the Tianjin
      area to study the contamination of DDT and its metabolites. Measurements were
      taken for p,p'-DDE, p,p'-DDD, p,p'-DDT, o,p'-DDE, o,p'-DDD and o,p'-DDT for all
      samples. The results indicated that p,p'-DDT and p,p'-DDE were the predominant
      contaminant compounds in the surface soil samples, with mean concentrations of
      27.5 and 18.8 ng g(-1) respectively. No significant differences in DDT
      concentrations were found between the soils from wastewater treated irrigated
      areas and other areas, suggesting that wastewater irrigation is not an important
      source of DDT in the area. However, the spatial distribution of soil DDTs levels
      in the area did correlate well with early direct application rates of pesticides.
      In addition, both pH level and organic carbon content are also known factors
      affecting the level of DDT and its metabolites. Although it was assumed that the
      use of these chemicals was banned in the early 1980s, the current concentration
      levels appear to be too high to be mere residuals after 20 years degradation.

PMID- 14664855
TI  - Effect of temperature and dissolved oxygen on the growth kinetics of Pseudomonas
      putida F1 growing on benzene and toluene.
AB  - Batch experiments were conducted to determine the effect of temperature and
      dissolved oxygen concentration on the rates of growth and substrate (benzene and
      toluene) degradation by the toluene degrading strain, Pseudomonas putida F1. Over
      a range of temperature from 15 to 35 degrees C the maximum specific growth rate
      followed the Topiwala-Sinclair relationship when either benzene or toluene served
      as the sole carbon and energy source. Oxygen limited growth followed Monod
      saturation kinetics with the specific growth rate given as a function of the
      dissolved oxygen concentration. The oxygen half-saturation coefficient was found
      to be approximately 1 mg/l regardless of whether benzene or toluene was the
      substrate. Similar experiments with Burkholderia (Ralstonia) pickettii PKO1 for
      grown on toluene revealed an oxygen half-saturation coefficient of 0.7 mg/l.

PMID- 14664856
TI  - Effects of ionic strength on the production of short chain volatile hydrocarbons
      by Dunaliella salina (Teodoresco).
AB  - The effect of ionic strength on the production of short chain volatile
      hydrocarbons was studied in cultures of Dunaliella salina. Axenic cultures of D.
      salina were grown at three different ionic strengths 0.5, 2 and 3 M of NaCl in
      Johnson (J/1) culture medium [Journal of Bacteriology 95 (1968) 1461] under the
      following laboratory growth conditions: a 12:12 h photoperiod, 300 micromolm(
      2)s(-1) of photosynthetic active radiation (PAR) provided by a fluorescent lamp
      of 40 W combined with a 100 W incandescent lamp at 20 +/- 1 degrees C at pH 7.5.
      C1 to C5 hydrocarbons were detected using a head space technique and GC-FID. Cell
      numbers and growth rate was greatest at 2 M NaCl 4.3 x 10(6) cellml(-1) after a
      15 days period of culture. Maximum hydrocarbon production was measured in the
      concentration of 0.5 NaCl with lower production rates in the more concentrated
      solutions. The principal hydrocarbon was pentane at 0.5 M but was ethane in 2 and
      3 M solutions. Production rates for individual compounds ranged between 0.13 and
      22 x 10(-15) microgCcell(-1)h(-1). It is suggested that the ability to produce
      and release volatile organic compounds of D. salina is related to osmotic
      conditions established by the ionic strength of growth solution.

PMID- 14664857
TI  - Enantioselective recognition of mono-demethylated methoxychlor metabolites by the
      estrogen receptor.
AB  - Metabolites of methoxychlor such as 2-(p-hydroxyphenyl)-2-(p-methoxyphenyl)-1,1,1
      trichloroethane (mono-OH-MXC) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane
      (bis-OH-MXC), have estrogenic activity. Mono-OH-MXC is a chiral compound in which
      the carbon atom bridging two benzene rings is the chiral centre. In previous
      studies the estrogenic activity of racemic mono-OH-MXC has been measured, and the
      activity of each enantiomer of this compound has not yet been elucidated. In this
      study, we evaluated the estrogen receptor-binding activity of each enantiomer of
      mono-OH-MXC to clarify the enantioselective recognition by the estrogen receptor.
      (S)-mono-OH-MXC showed 3-fold higher binding activity than that of the (R)
      enantiomer. The activity of bis-OH-MXC was only 1.7-fold higher than that of (S)
      mono-OH-MXC. This result suggests that the one hydroxy group and the orientation
      of the CCl3 group of mono- and bis-OH-MXCs are important for the interaction with
      the estrogen receptor. The result also points out the estrogenic activity of
      methoxychlor after metabolic activation in vivo, which predominantly produces the
      (S)-mono-OH-MXC, may be higher than estimated from the in vitro activity of
      racemic mixtures.

PMID- 14664858
TI  - Levels of "toxic" and "essential" metals in samples of bovine milk from various
      dairy farms in Calabria, Italy.
AB  - The aim of this research was to evaluate the possible contamination by heavy
      metals of milk from cows bred on various farms in Calabria. The concentrations of
      heavy metals were determined in 40 samples of bovine milk from the various dairy
      farms. Each sample, homogenized and powdered, was mineralized in a microwave
      oven. Quantitative analyses of Cd, Cr, Cu, Pb and Se were performed using an
      atomic absorption spectrophotometer with graphite furnace; As was analyzed by hot
      vapor generation technique and Zn with the flame method. As regards toxic heavy
      metals, highest values are those of As (g.m. 37.90 microg/kg w.w.) and Pb (g.m.
      1.32 microg/kg w.w.), while lowest concentrations are those of Cd (g.m. 0.02
      microg/kg w.w). With regard to essential metals, Zn (g.m. 2016 microg/kg w.w) and
      Se (g.m. 13.24 microg/kg w.w.) showed the highest concentrations, followed by Cr
      (g.m. 2.03 microg/kg w.w.) and Cu (g.m. 1.98 microg/kg w.w.). Further
      investigations of the levels of heavy metals (As) in a greater number of milk
      samples from various zones of Calabria are necessary, both to examine this
      problem from the clinical epidemiological point of view and to identify the
      possible causes of milk contamination.

PMID- 14664859
TI  - Polychlorinated biphenyl levels in adipose tissue of primiparous women in Turkey.
AB  - Polychlorinated biphenyls (PCBs) are a mixture of 209 possible congeners with
      different chlorine substitutions and they are potentially hazardous compounds in
      the environment for human beings. The high lipophilicity and the resistance to
      biodegradation of PCBs allow the bioaccumulation of these chemicals in the fatty
      tissues of organisms. The objective of this study was to determine the levels of
      PCBs in the adipose tissue of women living in Ankara, Turkey. For this purpose,
      levels of seven major persistent PCB congeners (IUPAC Numbers: 28, 52, 101, 118,
      138, 153, 180) were measured in 29 primiparous mothers' adipose tissue samples by
      gas chromatography with electron capture detection (GC-ECD). PCB IUPAC numbers
      138, 153 and 180 were the most abundant congeners, each accounting for > 20% of
      the total PCB content of adipose tissue. PCB 153 was the dominant congener in all
      the samples (141.7 +/- 132.3 ng/g lipid wt. basis). The results are compared with
      the similar studies from other countries. The concentrations of PCB 28, PCB 52
      and PCB 101 were found to be higher than those found in industrialized countries.
      This study is important in terms of being the first study of determination of PCB
      levels in adipose tissue samples in Turkey.

PMID- 14664860
TI  - Speciation of elements in sediment samples collected at lakes Volvi and Koronia,
      N. Greece.
AB  - A five-step sequential extraction procedure was applied for the determination of
      the distribution of seven elements (Cd, Pb, Cr, Cu, Mn, Zn, Fe) in sediment
      samples collected at two lakes, Volvi and Koronia, located in N. Greece. Samples
      were taken in two seasons, and the average concentration of the elements was
      calculated. The accuracy evaluated by comparing total trace metal concentrations
      with the sum of the five individual fractions proved to be satisfactory. Based on
      the results determined at one sampling point in Koronia and two sampling points
      along the lake Volvi, it seems that the two lakes have not yet been polluted.
      There were no significant changes in the individual seasonal concentrations of
      elements in this monitoring period. Cd, Pb, Cu and Cr are associated with the
      oxidizable, carbonates and residual fractions. Zn and Fe are associated with
      residual and reducible fractions. The metals that we most easily extracted in the
      samples analysed in both lakes are Pb, Cr, Cd, Cu and also Mn in the case of
      Koronia lake.

PMID- 14664861
TI  - Monitoring microbial biomass and respiration in different soils from the Czech
      Republic--a summary of results.
AB  - The microbial biomass (Cbio), respiration (basal respiration (BR) and potential
      respiration (PR)), and derived indices for 520 independent soil samples of 117
      different soils from the Czech Republic were statistically analysed. The broad
      range of soil samples allowed the stepwise breakdown of the database into six
      reasonable categories of soil: arable soils, loamy grassland soils, sandy
      grassland soils with weak organic matter content, sandy grassland soils with
      moderate organic matter content, forest soils with moderate organic matter
      content, and forest organic soils with rich organic matter content. Because soil
      microbiology lacks benchmarking values, the ranges of the microbial
      characteristics for these categories were stated and are presented here. The
      separation into soil groups narrowed the ranges enough to be useful for
      comparative purposes. The groups displayed significant differences in basal
      microbial parameters. The lowest microbial biomass was found in arable soils and
      grassland sandy soils with weak organic matter content. The highest microbial
      biomass was shown by loamy grassland soils and organic forest soils. Respiration
      displayed similar results to the microbial biomass. The derived indices revealed
      less significant differences confirming their inner-standard nature. The
      relationships between the soil contamination and microbial parameters were not
      explored because of the confounding effect of soil organic matter. However, it
      was not shown by the category of grassland sandy soils with weak organic matter
      content suggesting they could be especially suitable for the biomonitoring of
      harmful effects of chemicals on soil microorganisms.

PMID- 14664862
TI  - Irreversible sorption of pentachlorophenol to sediments: experimental
      observations.
AB  - The partitioning behavior of pentachlorophenol (PCP) in five sediments was
      studied using equilibrium sorption experiments and multiple cycles of sorption
      and desorption experiments. The results of the equilibrium sorption experiments
      showed that the isotherms of PCP on five sediments were linear and the
      partitioning coefficients (Kd) were proportional to the organic carbon content of
      the sediments. The average organic carbon content normalized partitioning
      coefficient (logK oc) of five sediments was 2.83 +/- 1.48. In multiple cycles of
      sorption and desorption experiments, the five sediments were found to exhibit
      statistically significant sorption-desorption hysteresis, and the hysteresis
      indices (HI) varied over a wide range (0.72 - 11.82). Correlations between the HI
      value and the percentage of lipid in the total organic matter in the sediment
      indicated that lipid was the main fraction to affect the hysteresis phenomenon,
      i.e., the higher the lipid percentage the greater the HI value. The hysteresis
      phenomenon was mostly caused by irreversible sorption of PCP on lipids, including
      entrapment by lipids, which induced the slow desorption rate from the sediment.
      Because of hysteresis in the sorption and desorption, the PCP ecological toxicity
      would be lower than expected.

PMID- 14664863
TI  - Allozyme polymorphisms and heavy metal levels in the green-lipped mussel Perna
      viridis (Linnaeus) collected from contaminated and uncontaminated sites in
      Malaysia.
AB  - It has been widely reported that heavy metal contamination in coastal waters can
      modify the allozyme profiles of marine organisms. Previous studies have recorded
      elevated metal concentrations in sediments and mussel tissues off Peninsular
      Malaysia. In the present study, horizontal starch gel electrophoresis was carried
      out to estimate the levels of allelic variation of the green-lipped mussel, Perna
      viridis, collected from one contaminated and three relatively uncontaminated
      sites off Peninsular Malaysia. Fourteen polymorphic loci were observed. In
      addition, the concentrations of cadmium, copper, lead, mercury and zinc were
      determined in the sediments and in the soft tissues of the mussels. Mussels from
      contaminated site, evidenced by high metal pollution indices (MPI) of the
      sediment and the mussel tissues, showed the highest percentage of polymorphic
      loci (78.6%), while those collected from the uncontaminated sites had lower MPI
      of the sediment and mussel tissue, and exhibited lower percentages of polymorphic
      loci (35.7-57.1%). The population from the contaminated site showed the highest
      excess of heterozygosity (0.289) when compared to that of the populations from
      the three uncontaminated sites (0.108-0.149). Allozyme frequencies at the
      phosphoglucomutase (PGM; E.C. 2.7.5.1) locus also differed between the
      contaminated and uncontaminated populations. Previous studies have shown that
      exposure to heavy metals can select or counter-select for particular alleles at
      this locus. The present results suggest that allozyme polymorphism in P. viridis
      is a potential biomonitoring tool for heavy metal contamination but further
      validation is required.

PMID- 14664864
TI  - Disinfection of wastewater with peracetic acid: a review.
AB  - Peracetic acid is a strong disinfectant with a wide spectrum of antimicrobial
      activity. Due to its bactericidal, virucidal, fungicidal, and sporicidal
      effectiveness as demonstrated in various industries, the use of peracetic acid as
      a disinfectant for wastewater effluents has been drawing more attention in recent
      years. The desirable attributes of peracetic acid for wastewater disinfection are
      the ease of implementing treatment (without the need for expensive capital
      investment), broad spectrum of activity even in the presence of heterogeneous
      organic matter, absence of persistent toxic or mutagenic residuals or by
      products, no quenching requirement (i.e., no dechlorination), small dependence on
      pH, short contact time, and effectiveness for primary and secondary effluents.
      Major disadvantages associated with peracetic acid disinfection are the increases
      of organic content in the effluent due to acetic acid (AA) and thus in the
      potential microbial regrowth (acetic acid is already present in the mixture and
      is also formed after peracetic acid decomposition). Another drawback to the use
      of peracetic acid is its high cost, which is partly due to limited production
      capacity worldwide. However, if the demand for peracetic acid increases,
      especially from the wastewater industry, the future mass production capacity
      might also be increased, thus lowering the cost. In such a case, in addition to
      having environmental advantages, peracetic acid may also become cost-competitive
      with chlorine.

PMID- 14664865
TI  - Cadmium biosorption by cells of Spirulina platensis TISTR 8217 immobilized in
      alginate and silica gel.
AB  - The biosorption of cadmium by immobilized Spirulina platensis on alginate gel and
      silica gel was studied. The maximum biosorption capacities for alginate
      immobilized cells and silica immobilized cells were 70.92 and 36.63 mg Cd/g
      biomass, respectively. Temperature did not have an influence on metal sorption,
      whereas an initial pH solution did. Sorption occurred in a wide pH range (pH 3
      8). The highest adsorption of alginate immobilized cells was at pH 6, while
      silica immobilized cell adsorption was not affected at pH between 4 and 7. The
      immobilized cells were reused in consecutive adsorption-desorption. The results
      showed that immobilized cells could be repeatedly used in the sorption process up
      to five times.

PMID- 14664866
TI  - Plant community tolerant to trace elements growing on the degraded soils of Sao
      Domingos mine in the south east of Portugal: environmental implications.
AB  - The selection of trace element tolerant species is a key factor to the success of
      remediation of degraded mine soils. Mining activities generate a large amount of
      waste rocks and tailings, which get deposited at the surface. The degraded soils,
      the waste rocks and tailings are often very unstable and will become sources of
      pollution. The direct effects will be the loss of cultivated land, forest or
      grazing land, and the overall loss of production. The indirect effects will
      include air and water pollution and siltation of rivers. These will eventually
      lead to the loss of biodiversity, amenity and economic wealth. Restoration of a
      vegetation cover can fulfil the objectives of stabilization, pollution control,
      visual improvement and removal of threats to human beings. Thus, remediation of
      mine spoils/tailings and biogeochemical prospecting would rely on the appropriate
      selection of plant species. Plant community responds differently on their ability
      to uptake or exclude a variety of metals. In this work, plant species were
      sampled from all populations established in an abandoned copper mine of Sao
      Domingos, SE Portugal. Plants belonging to 24 species, 16 genera and 13 families
      were collected from the degraded copper mine of Sao Domingos. Plant samples were
      analysed for total Ag, As, Cu, Ni, Pb, and Zn. The highest concentrations of
      metals in soils dry matter were 11217.5 mg Pb kg(-1), 1829 mg Cu kg(-1), 1291 mg
      As kg(-1), 713.7 mg Zn kg(-1), 84.6 mg Cr kg(-1), 54.3 mg Co kg(-1), 52.9 mg Ni
      kg(-1) and 16.6 mg Ag kg(-1). With respect to plants, the higher concentrations
      of Pb and As were recorded in the semi-aquatic species Juncus conglomeratus with
      84.8 and 23.5 mg kg(-1) dry weight (DW), Juncus efusus with 22.4 and 8.5 mg kg(
      1) DW, and Scirpus holoschoenus with 51.7 and 8.0 mg kg(-1) DW, respectively.
      Thymus mastichina also showed high content of As in the aboveground parts, 13.6
      mg kg(-1) DW. Overall, the results indicate accumulation of various metals by
      different plant species, with some of these metals being partitioned to the
      shoots. Environmental implications of these observations are discussed.

PMID- 14664867
TI  - Atmospheric versus lithogenic contribution to the composition of first- and
      second-order stream waters in Seoul and its vicinity.
AB  - The spatial variations in the chemistry of first- and second-order stream waters
      (N = 65) were investigated in the easterly bound of Seoul in order to assess the
      effects of urban air pollution on surface water chemistry. The sulfate (SO4(2-))
      was high (range 3.9-17.8 mg l(-1), mean 11.8 mg l(-1)) within 30 km away from the
      center of Seoul, compared to the levels (range 1.1-7.7 mg l(-1), mean 4.3 mg l(
      1)) observed in remote areas (30-70 km away). Both graphical examination and
      statistical evaluation (variogram) of sulfate concentration data consistently
      showed the decrease of sulfate concentration with increasing distance. The
      results of mass balance modeling also indicate that the concentrations of SO4(2
      ), Cl- and Na+ may be affected mainly by dry/wet deposition. However, the spatial
      variations of major cations such as Ca2+ and Na+ are well explained by the
      reaction of rainwater with diverse rocks in the watercourse. The water type was
      found to change from Ca(-Na)-SO4) type to Ca(-a)-HCO3 type with the increasing
      distance. It is thus inferred that the pollutants like SO2 emitted from strong
      man-made source areas of Seoul are transported to the considerable distance (at
      least 30 km away) by westerlies and that such mechanism may lead to the changes
      of the anion composition in surface water. In the remote area (> 30 km away from
      Seoul), the stream water chemistry appears to be influenced more effectively by
      the weathering of rock-forming minerals.

PMID- 14664868
TI  - Partitioning of trace metals between soft tissues and shells of Patella aspera.
AB  - This paper describes the partitioning of iron, manganese, zinc, copper, cadmium,
      cobalt, nickel and lead between the soft tissues and the shells of the gastropod
      mollusc Patella aspera. Specimens of the limpet P. aspera were collected from a
      clean coastal marine site (CMS) and from an estuarine contaminated site (ECS) on
      the south coast of Portugal. Fe and Zn concentrations were significantly lower on
      both populations and less variable in the shells than in the soft tissues. In
      contrast Mn concentrations were higher in the shells than in the soft tissues at
      ECS. The partitioning factor (PF), defined as the ratio between the mean metal
      concentrations in soft tissues and in the shells, was maximum for iron and
      minimum for manganese. Between the soft tissues and the shells, only manganese at
      ECS recorded a significant relationship between metal concentrations, suggesting
      that the mechanism that controls the accumulation of this essential metal in both
      tissues was different from the others. From the obtained data, in biomonitoring
      sewage contamination studies, shells of P. aspera can be considered as a good
      indicator for Mn while the soft tissues for Zn. As copper, cadmium, nickel and
      cobalt concentrations were much higher in the soft tissues than in the shells (<
      0.1 microg g(-1)), this indicates that the shells were not a good indicator for
      these metals because they do not reflect the environmental bioavailability as do
      the soft tissues.

PMID- 14664869
TI  - Environmental impact of unleaded gasolines in the bay of Cadiz (Spain).
AB  - Given the strategic situation of the Jose Leon de Carranza bridge, which spans
      the Bay of Cadiz (in the SW of Spain) and carries very heavy motor traffic,
      together with knowledge of the currents and tidal flows in the zone, we have used
      a technique of radioactive dating of sediments to study the temporal evolution
      presented by contamination from lead in the sediment column. This has allowed us
      to observe the environmental impact, in terms of the concentration of Pb in the
      sea bed sediments, that has been produced in the zone by the introduction of
      unleaded gasolines as substitutes for traditional automobile fuels that employ
      organic forms of tetra methyl lead as an antidetonant agent in the fuel.

PMID- 14664870
TI  - Nutrient chemistry of River Pinios (Thessalia, Greece).
AB  - The impact of human activities with 3-year monitoring on the fluctuation of
      nutrients along the Pinios River and its tributaries were studied. Their seasonal
      variations throughout the years 1996-1998 were also presented. High temperatures,
      from June to August, cause a restriction of the water flow, an enhancement of
      nutrient concentration with the subsequent increase of eutrophication. High
      concentrations of nutrients were observed first in winter (wet period), caused by
      leaching of fertilizers from terrestrial systems after heavy rainfall, later
      during the warm months due to low water flow of the river, and at last in autumn
      when plant organisms began to decompose. The intensive algal and macrophyte
      growth (spring, summer) resulted in severe depletion of nutrients. Organic carbon
      showed no seasonal trend but its values were high near the estuaries. Nitrate
      fluxes were high at the initial station (sources) and the Titarisios tributary,
      whereas nitrites and ammonium were low. In contrary, the Kalentzis tributary with
      relatively low nitrate values showed increased values of nitrite ammonium or
      total nitrogen. On the other hand, the Enipeas tributary showed high SO4 values.
      Phosphates are remarkably present mainly after the city of Larissa, where sewage
      and industrial discharges occur. None of the nutrients measured in the Pinios
      River and its tributaries showed a clear seasonal cycle of concentration.
      Concentrations of nutrients and organic carbon increased as a consequence of
      anthropogenic inputs, particularly point discharges from sewage treatment plants
      (i.e. showing distinct, but variable, concentration peaks), as well as diffuse
      urban and/or agricultural runoff over long areas during storm events. The
      agricultural management, the urban pollution, mainly from Larissa City, and the
      climate conditions in the catchment basin (Thessalia Plain) of Pinios River and
      its tributaries greatly affect the chemical composition of their waters.

PMID- 14664871
TI  - Development of a rapid method for direct detection of tet(M) genes in soil from
      Danish farmland.
AB  - A method for direct detection of antibiotic resistance genes in soil samples has
      been developed. The tetracycline resistance gene, tet(M), was used as a model.
      The method was validated on Danish farmland soil that had repeatedly been treated
      with pig manure slurry containing resistant bacteria. The tet(M) gene was
      directly detected in 10-80% of the samples from the various farmland soils and
      could be detected in all samples tested after selective enrichment. To validate
      the obtained results, the method was applied to garden soil samples where lower
      prevalence of resistance was found. RESULT: A detection limit of 10(2)-10(3)
      copies of the tet(M) gene per gram of soil (in a Bacillus cereus group bacterium)
      was achieved. tet(M) gene was detected in soil samples with the highest
      prevalence on farmland treated with pig manure slurry.

PMID- 14664872
TI  - Environmental and health consequences of depleted uranium use in the 1991 Gulf
      War.
AB  - Depleted uranium (DU) is a by-product of the 235U radionuclide enrichment
      processes for nuclear reactors or nuclear weapons. DU in the metallic form has
      high density and hardness as well as pyrophoric properties, which makes it
      superior to the classical tungsten armour-piercing munitions. Military use of DU
      has been recently a subject of considerable concern, not only to radioecologists
      but also public opinion in terms of possible health hazards arising from its
      radioactivity and chemical toxicity. In this review, the results of uranium
      content measurements in different environmental samples performed by authors in
      Kuwait after Gulf War are presented with discussion concerning possible
      environmental and health effects for the local population. It was found that
      uranium concentration in the surface soil samples ranged from 0.3 to 2.5 microg
      g(-1) with an average value of 1.1 microg g(-1), much lower than world average
      value of 2.8 microg g(-1). The solid fallout samples showed similar
      concentrations varied from 0.3 to 1.7 microg g(-1) (average 1.47 microg g(-1)).
      Only the average concentration of U in solid particulate matter in surface air
      equal to 0.24 ng g(-1) was higher than the usually observed values of
      approximately 0.1 ng g(-1) but it was caused by the high dust concentration in
      the air in that region. Calculated on the basis of these measurements, the
      exposure to uranium for the Kuwait and southern Iraq population does not differ
      from the world average estimation. Therefore, the widely spread information in
      newspapers and Internet (see for example: [CADU NEWS, 2003.
      http://www.cadu.org.uk/news/index.htm (3-13)]) concerning dramatic health
      deterioration for Iraqi citizens should not be linked directly with their
      exposure to DU after the Gulf War.

PMID- 14664873
TI  - Differences in episiotomy technique between midwives and doctors.
AB  - OBJECTIVES: To examine the practice of making an episiotomy and to determine any
      differences in practice between professional groups. DESIGN: A prospective
      survey. SETTING: A large tertiary referral obstetric hospital and the obstetric
      department of a district general hospital. POPULATION: All staff routinely
      involved in the care of women in labour. METHODS: A novel validated pictorial
      questionnaire was designed, validated and distributed to the study population.
      Differences in outcome measures were compared by profession and by seniority.
      MAIN OUTCOME MEASURES: Measurements taken from the questionnaire: the length of
      episiotomy drawn; the distance from the sagittal plane at which the episiotomy
      was begun; and the angle of the episiotomy from the sagittal plane. RESULTS:
      Fifty doctors and 78 midwives completed the forms. Median distance of the
      episiotomy from the midline was 0 mm (-2 to 11). Episiotomies drawn by doctors
      were significantly longer and more angled than those drawn by midwives (P = 0.002
      and P = 0.001). Sixteen percent of doctors and 1% of midwives drew an episiotomy
      longer than 20 mm (difference 15%, 95% CI 6 to 24). Twenty-three percent of
      midwives and 2% of doctors drew an episiotomy angled 30 degrees or less
      (difference 21%, 95% CI 9 to 34). CONCLUSIONS: This study has demonstrated
      differences in the reporting of episiotomy practice by doctors and midwives.
      Theoretically, the differences demonstrated could predispose to a greater risk of
      anal sphincter injuries. These data need to be confirmed by observational studies
      of actual practice and by studies to investigate the mechanics of sphincter
      injury during childbirth.

PMID- 14664874
TI  - Effectiveness of nifedipine versus atosiban for tocolysis in preterm labour: a
      meta-analysis with an indirect comparison of randomised trials.
AB  - OBJECTIVE: To explore the effectiveness of nifedipine compared with atosiban for
      tocolysis in preterm labour. DESIGN: A systematic review of randomised controlled
      trials with meta-analysis using adjusted indirect comparison. POPULATION: Six
      hundred and seventy-nine women recruited in nine randomised trials evaluating the
      effectiveness of nifedipine versus beta-agonists, and 852 women recruited in four
      trials of atosiban versus beta-agonists. There were no trials comparing
      nifedipine directly with atosiban. METHODS: We performed meta-analysis with a
      technique involving an adjusted indirect comparison between nifedipine and
      atosiban using beta-agonists as the common comparator. This approach preserves
      the benefit accrued by randomisation in the original comparisons. MAIN OUTCOME
      MEASURES: Reduction in neonatal respiratory distress syndrome and delay in
      delivery by 48 hours. RESULTS: Nifedipine tocolysis was associated with a
      significant reduction in respiratory distress syndrome compared with atosiban (OR
      0.55, 95% CI 0.32-0.97). It also increased the number of women whose delivery was
      delayed by 48 hours (OR 1.20, 95% CI 0.73-1.95), although this result was not
      statistically significant. CONCLUSIONS: When indirectly compared with atosiban,
      nifedipine tocolysis is more effective. In the absence of a direct comparison,
      our analysis provides a way to explore the potential benefits of nifedipine
      versus atosiban.

PMID- 14664875
TI  - The effects of metabolic inhibition on intracellular calcium and contractility of
      human myometrium.
AB  - OBJECTIVE: Hypoxia occurs in the uterus during labour and may contribute to
      dysfunctional labours. We wanted to establish its effects on pregnant human
      myometrium and elucidate the mechanisms involved. DESIGN: Scientific study.
      SETTING: University Hospital and laboratories. POPULATION OR SAMPLE: Term
      pregnant women. METHODS: We measured contractions and intracellular [Ca(2+)]
      ([Ca(2+)](i)), in biopsies from term pregnant women undergoing elective caesarean
      section, and used cyanide to block oxidative phosphorylation. MAIN OUTCOME
      MEASURES: Changes in contractility and calcium. RESULTS: Although basal levels of
      [Ca(2+)](i) and tone rose, spontaneous and agonist-induced Ca(2+) transients and
      phasic contractions were rapidly reduced and abolished by cyanide. Neither
      stimulation of the uterus with oxytocin nor the Ca channel agonist, Bay K8644,
      prevented the changes produced by cyanide. The tonic force produced by
      depolarising the myometrium was also decreased by cyanide, but slowly recovered
      towards control levels, whereas [Ca(2+)](i) was maintained throughout. Similar
      data were obtained when nitrogen, rather than cyanide, was applied to the
      depolarised uterus. CONCLUSIONS: Impairment of oxidative phosphorylation is a
      potent depressor of phasic activity in human myometrium, irrespective of how it
      is produced, and our data suggest its effects lie at and beyond the surface
      membrane. Stimulation of the hypoxic uterus was not effective, which may explain
      the unpredictability of oxytocin application in some dysfunctional labours.

PMID- 14664876
TI  - Randomised controlled study comparing oral and vaginal misoprostol for cervical
      priming prior to surgical termination of pregnancy.
AB  - OBJECTIVE: To compare the effectiveness of oral misoprostol with vaginal
      misoprostol as a cervical priming agent prior to first trimester vacuum
      aspiration. DESIGN: Randomised study. SETTING: Scottish teaching hospital.
      POPULATION: Primigravid women at gestations up to 91 days requesting surgical
      abortion under the 1967 Abortion Act. METHODS: Sixty-four women were randomised
      to receive misoprostol 400 microg orally at home or vaginally in hospital 2-4
      hours pre-operatively for cervical priming. MAIN OUTCOME MEASURES: The main
      outcome measures were cumulative force required to dilate the cervix to 9 mm,
      baseline cervical dilatation, intra-operative blood loss and patient and staff
      acceptability. RESULTS: There was no significant difference in baseline cervical
      dilatation, peak force required to dilate the cervix at 8 and 9 mm and cumulative
      force required between the two groups. Operating time and intra-operative blood
      loss were not significantly different between the two groups. The priming to
      abortion interval was significantly longer with oral misoprostol when compared
      with the vaginal group (P < 0.0001). Women receiving oral misoprostol were
      significantly more likely to experience nausea (OR: 3.9, 95% CI: 1.3 to 11.2),
      while women receiving vaginal misoprostol were more likely to complain of
      tiredness (OR: 0.2, 95% CI: 0.1 to 0.7) with no significant differences in other
      side effects between the two groups. There was no significant difference in
      patient acceptability in relation to the priming agent between the two groups (P
      = 0.96). However, majority of the nursing staff (83%) admitting women preferred
      the oral route of administration. CONCLUSION: Cervical priming with oral
      misoprostol at home is effective with high patient and staff acceptability.

PMID- 14664877
TI  - The use of video information in obtaining consent for female sterilisation: a
      randomised study.
AB  - HYPOTHESIS: Providing additional information by video in addition to the standard
      consultation in women requesting sterilisation increases patients' knowledge
      about the procedure with no change in anxiety levels. DESIGN: Randomised control
      trial in 6 weeks. POPULATION: Women requesting sterilisation (n = 31). SETTING:
      Gynaecology clinics in two teaching hospitals. METHODS: Comparison of providing
      additional information by video in addition to the standard consultation with the
      standard consultation. MAIN OUTCOME MEASURES: Patients' knowledge of
      sterilisation, anxiety levels and acceptance of the video approach. RESULTS:
      Women receiving video information as well as the standard consultation had
      significantly higher knowledge scores compared with women only receiving the
      conventional consultation. Women undergoing a conventional consultation (no
      video) in a nurse-led dedicated sterilisation clinic had significantly higher
      knowledge scores than women having their consultation in a general gynaecological
      clinic. There were no differences in anxiety levels between the groups.
      Information giving by video was acceptable to the majority of women. CONCLUSION:
      Videos are a reliable and consistent method of delivering information to women
      requesting female sterilisation.

PMID- 14664878
TI  - Ovulation induction with a starting dose of 50 IU of recombinant follicle
      stimulating hormone in WHO group II anovulatory women: the IO-50 study, a
      prospective, observational, multicentre, open trial.
AB  - OBJECTIVE: To assess the efficacy and safety in clinical practice of a low dose
      regimen of 50 IU of recombinant follicle stimulating hormone in induction of
      ovulation. DESIGN: Prospective, observational, non-comparative, open, multicentre
      study. SETTING: Eighty-eight infertility clinics and teaching hospital fertility
      units throughout Spain. POPULATION: Women with normogonadotrophic chronic
      anovulation (WHO group II) with or without echographic diagnosis of polycystic
      ovary syndrome. METHODS: Low dose step-up protocol of recombinant follicle
      stimulating hormone administration (follitropin beta, Puregon) with a starting
      dose of 50 IU and weekly increments according to follicular response monitored
      prospectively by transvaginal ultrasonography. Patients were followed for a
      minimum of one cycle and a maximum of six. MAIN OUTCOME MEASURES: Rate and size
      of follicular growth, cumulative ovulation rate, follicle stimulating hormone
      doses and duration of treatment, pregnancy and cycle cancellation rate, ovarian
      hyperstimulation syndrome and multiple pregnancy. RESULTS: A total of 945
      treatment cycles were evaluated. In 817 cycles, ovulation was induced with human
      chorionic gonadotrophin (hCG) and in 501 (61.3%) unifollicular development (a
      follicle of > or =18 mm) was achieved. A total of 128 cycles (13.5%) were
      cancelled because of ovarian hyper-responsiveness or spontaneous ovulation. The
      cumulative ovulation rate (confirmed by mid-luteal serum progesterone
      concentrations) after six treatment cycles was 84%. There were 136 clinical
      pregnancies (14.4% pregnancies per cycle). The cumulative pregnancy rate after
      six treatment cycles was 53.1%. Eight twin pregnancies occurred. Thirteen women
      miscarried and there were two cases of ectopic pregnancies. The median of average
      daily doses of follitropin beta in all cycles was 50 IU. Between 68% and 86% of
      patients received treatment with follitropin beta for a maximum of 14 days.
      Ovarian hyperstimulation syndrome occurred in 64 (6.8%) cases but no case of
      severe ovarian hyperstimulation developed. CONCLUSIONS: Low dose regimen of 50 IU
      of recombinant follicle stimulating hormone (Puregon) is efficient, safe and well
      tolerated for inducing follicular development in WHO group II anovulatory women.

PMID- 14664879
TI  - The association of socio-economic position across the life course and age at
      menopause: the British Women's Heart and Health Study.
AB  - OBJECTIVE: To assess the association of indicators of adverse socio-economic
      position from across the life course with age at menopause. DESIGN: Cross
      sectional study as part of the British Women's Heart and Health Study. SETTING:
      23 British towns. POPULATION: Three thousand and five hundred and thirteen women
      aged 60-79 years from a total cohort of 4286. Women who underwent a hysterectomy
      or oophorectomy prior to their 'natural' menopause or who were taking hormone
      replacement therapy around the perimenopausal period and for whom a biological
      age at menopause could not be calculated were excluded from this study. MAIN
      OUTCOME MEASURES: Age at menopause. RESULTS: Most of the 10 indicators of adverse
      socio-economic position from childhood through to adulthood were linearly
      associated with a younger age at menopause. In age adjusted analyses, women from
      manual social classes in childhood began their menopause on average 0.68 years
      (95% confidence interval [CI] 0.11, 1.3) earlier than those from non-manual
      social classes. Those who lived in a house as a child without a bathroom began
      their menopause 0.47 years (95% CI 0.12, 0.82) earlier than those with a
      bathroom. Those who shared a bedroom began 0.36 years (95% CI 0.03, 0.70) earlier
      than those who had their own bedroom and finally those who lived in a household
      with no access to a car as a child began their menopause 0.47 years (95% CI 0.02,
      0.95) earlier than those with access to a car. Adult indicators of adverse socio
      economic position were similarly associated with earlier age at menopause. Age at
      completing full time education was not substantively associated with age at
      menopause. The inverse associations between each of the indicators of both
      childhood and adult socio-economic position and age at menopause were not
      importantly affected by adjustment for other reproductive factors but they
      attenuated by between 6% and 21% with adjustment for adult smoking and body mass
      index. The inverse associations between each of the childhood indicators of socio
      economic position only and age at menopause attenuated markedly (between 12% and
      70%) with adjustment for adult leg length. There was a cumulative effect of
      disadvantage across the life course demonstrated by a strong linear trend between
      a composite score of the 10 socio-economic indicators and young age at menopause.
      The age at onset of menopause for women who had 9 or 10 adverse socio-economic
      indicators was on average 1.70 years (95% CI 0.36, 3.0) younger than that of
      women with none or only one indicator. CONCLUSIONS: Adverse socio-economic
      circumstances in childhood, as well as in adulthood, are associated with an
      earlier age at menopause. The association between childhood deprivation and early
      menopause may at least in part be mediated via exposures, such as childhood diet,
      which affect both linear growth and age at menopause.

PMID- 14664880
TI  - Randomised controlled trial of total compared with subtotal hysterectomy with one
      year follow up results.
AB  - OBJECTIVE: To compare total abdominal hysterectomy and subtotal abdominal
      hysterectomy performed for benign uterine diseases. DESIGN: Randomised,
      controlled, unblinded trial with central, computer-generated randomisation.
      SETTING: Danish trial performed in 11 departments of gynaecology. POPULATION:
      Women referred for benign uterine diseases were randomised to total abdominal
      hysterectomy (n = 158) or subtotal abdominal hysterectomy (n = 161). One-year
      follow up questionnaires had a response rate of 87%. METHODS: Patients were
      followed by strict data collection procedures, including postal questionnaires.
      The results after one year of follow up were analysed by intention-to-treat
      analyses. MAIN OUTCOME MEASURES: (1) Primary: urinary incontinence and (2)
      secondary: post-operative complications, quality of life (SF-36), constipation,
      prolapse of the vaginal vault/cervical stump, satisfaction with sexual life,
      pelvic pain and vaginal bleeding. RESULTS: A significantly (P = 0.043) smaller
      proportion of women had urinary incontinence one year after total abdominal
      hysterectomy compared with subtotal abdominal hysterectomy [9% vs 18% (OR 2.08,
      95% CI 1.01-4.29)]. The lower proportion of incontinent women in the total
      abdominal hysterectomy group was a result of a higher proportion of symptom
      relief (total abdominal hysterectomy: 20/140, subtotal abdominal hysterectomy:
      14/136) as well as a lower proportion of women with new symptoms (total abdominal
      hysterectomy: 3/140, subtotal abdominal hysterectomy: 10/137). Twenty-seven women
      (20%) from the subtotal abdominal hysterectomy group had vaginal bleeding and two
      of them had to have their cervix removed. No other clinically important
      differences were found between the two hysterectomy methods. CONCLUSIONS: A
      smaller proportion of women suffered from urinary incontinence after total
      abdominal hysterectomy than after subtotal abdominal hysterectomy one year post
      operatively.

PMID- 14664881
TI  - The ATAC adjuvant breast cancer trial in postmenopausal women: baseline
      endometrial subprotocol data.
AB  - OBJECTIVE: The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a
      randomised, double-blind trial comparing 'Arimidex' (anastrozole), alone or in
      combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant
      treatment for postmenopausal women with early breast cancer. Because tamoxifen is
      associated with endometrial pathology, the ATAC endometrial subprotocol was
      initiated to establish the background prevalence of pathology, and to assess
      prospectively the incidence and nature of intrauterine changes before and
      following endocrine therapy. SETTING: International. POPULATION AND STUDY DESIGN:
      Two hundred and eighty-five women entered the subprotocol: the mean age was 60
      years (range 44-80 years); 113 women (40%) had taken hormone replacement therapy
      prior to randomisation, and 238 women were parous (84%). The age at onset of the
      menopause was 32-58 years, with the majority becoming menopausal between 46 and
      55 years of age. Two hundred and seventy-two women had a hysteroscopy before they
      commenced trial medication. Hysteroscopy was performed successfully in 265 women.
      In six women, failure of hysteroscopy at baseline led to withdrawal from the
      study. Three of the women who withdrew had a pipelle biopsy taken. Therefore, the
      total number of endometrial biopsies at baseline was 268. MAIN OUTCOME MEASURES:
      To assess the demographic characteristics of women entering the endometrial
      subprotocol and their hysteroscopic and histological findings before commencing
      trial medication. RESULTS: At hysteroscopy, there was a diagnosis of endometrial
      polyps in 34 women (13%), fibroids in 16 women (6%) and one case of suspicious
      endometrium, which was confirmed as a polyp on histology. Only 21 of the 34
      polyps seen hysteroscopically were proven histologically (62% accuracy of
      hysteroscopy). Final histology found the prevalence of endometrial diagnostic
      categories as follows: 123 inactive endometrium (46%), 20 benign polyps (7%), 17
      secretory endometrium (6%), 7 proliferative endometrium (3%), 3 atypical
      hyperplasia (2 in a polyp), 1 simple hyperplasia (in a polyp) and 1 fibroid. The
      remaining women had pipelle samples with insufficient tissue obtained, indicating
      a normal endometrial cavity. CONCLUSION: This is the first study of such size in
      gynaecologically asymptomatic breast cancer patients. This paper describes the
      findings in individual patients before any trial treatment was given. In this
      baseline group, 82% (219/268) of women had a normal endometrial cavity; 18%
      (49/268) had endometrial activity (proliferative or secretory endometrium in 9%)
      or an intracavity abnormality (hyperplasia, polyps and a fibroid in 9%). In
      total, 36% of biopsies had insufficient tissue for diagnosis, which in
      combination with a normal hysteroscopy was classed as normal. The appearance of a
      polyp hysteroscopically in this group was not proven histologically in
      approximately 40% of cases. The development of uterine pathology over time in the
      ATAC study will subsequently be assessed against the findings of this baseline
      paper.

PMID- 14664882
TI  - Stress incontinence and pelvic floor neurophysiology 15 years after the first
      delivery.
AB  - HEADLINE: This is a longitudinal study of a cohort of primigravidae recruited
      between 1985 and 1987 and followed up 7 and 15 years later. Pelvic floor
      neurophysiology was performed and questionnaires were administered to determine
      the natural history of stress incontinence and to establish whether pelvic floor
      denervation after the first delivery is associated with symptoms of stress
      urinary incontinence in the future. OBJECTIVES: To study the natural history of
      stress urinary incontinence arising during the first pregnancy, to determine
      whether postnatal pelvic floor denervation progresses with time and whether it
      predisposes to stress urinary incontinence in the future. DESIGN: Prospective
      longitudinal cohort study. SETTING: Tertiary referral urogynaecology unit.
      SAMPLE: Cohort of 96 primigravidae studied prospectively between 1985 and 1987
      and followed up 7 years (n = 76) and 15 years (n = 55) later. METHODS: Urinary
      incontinence symptoms were recorded and pelvic floor neurophysiology was
      performed antenatally and postnatally between 1985 and 1987. Repeat
      neurophysiological tests and questionnaires were completed by those relocated 7
      and 15 years later. MAIN OUTCOME MEASURE: Symptoms of stress urinary
      incontinence. SECONDARY OUTCOMES: Symptoms of urge urinary incontinence and anal
      incontinence; motor unit potential duration and pudendal nerve terminal latency;
      vaginal squeeze pressure measured by perineometry. RESULTS: Prevalence of stress
      incontinence was highest during pregnancy and had increased seven years after the
      first postnatal period (P = 0.0129). Two-thirds of women with antenatal stress
      incontinence had stress incontinence 15 years later. One-third of women with
      stress incontinence at any time appear to undergo resolution of symptoms. Motor
      unit potential duration increased at seven years (P = 0.036). Vaginal squeeze
      pressure improved during the same period (P = 0.0007). CONCLUSIONS: When stress
      urinary incontinence arises during the first pregnancy, the risk of stress
      incontinence occurring 15 years later is doubled. Although pelvic floor
      reinnervation progressed after the postnatal period, the absence of an adequate
      marker for pelvic floor denervation makes it of uncertain clinical significance.

PMID- 14664883
TI  - Purohit technique of vaginal hysterectomy: a new approach.
AB  - To ease intra-operative access to laterally at vaginal hysterectomy, we have
      developed the 'Purohit technique of vaginal hysterectomy' using a right angle
      forceps, electrocautery and 10 mm telescope with light source. A prospective
      study on consecutive 214 women with benign disease of the uterus without
      prolapse, including cases with relative contraindications (excluding
      endometriosis and uteri above 20 weeks size), demonstrated it to be easy, safe
      and effective. Vaginal hysterectomy was successfully completed in 213 (99.53%)
      cases, with one failure (0.46%) which needed laparoscopic assistance. Vaginal
      salpingo-oophorectomy was completed in all indicated cases. We believe that many
      abdominal and laparoscopic hysterectomies could be avoided by this technique.
      Details of the technique can be seen on the following website
      http://www.purohittechnique.com

PMID- 14664884
TI  - Emergency use of a transfemoral aortic occlusion catheter to control massive
      haemorrhage at caesarean hysterectomy.

PMID- 14664885
TI  - Vulval cytomegalovirus coexisting with herpes simplex virus in a patient with
      human immunodeficiency virus infection.

PMID- 14664886
TI  - The spontaneous reversal of pre-eclampsia associated with parvovirus-induced
      hydrops and the placental theory of pre-eclampsia: a case report.

PMID- 14664887
TI  - Magnetic resonance imaging of vasa praevia.

PMID- 14664888
TI  - Peritoneal tuberculosis revealed by carcinomatosis on CT scan and uptake at FDG
      PET.

PMID- 14664889
TI  - Cornual pregnancy successfully treated by suction curettage and operative
      hysteroscopy.

PMID- 14664890
TI  - Mitotically active cervical leiomyoma in a non-HIV immunosuppressed case.

PMID- 14664891
TI  - The association between female genital cutting and correlates of sexual and
      gynaecological morbidity in Edo State, Nigeria.

PMID- 14664892
TI  - Serious fetal intracranial haemorrhage associated with the vacuum extraction.

PMID- 14664893
TI  - Uterine artery embolisation for symptomatic fibroids: clinical results in 400
      women with imaging follow up.

PMID- 14664894
TI  - Clinical manifestations and abnormal laboratory findings in pregnant women with
      primary cytomegalovirus infection.

PMID- 14664896
TI  - Asymmetric dimethylarginine (ADMA): a key regulator of nitric oxide synthase.

PMID- 14664897
TI  - Old and new cardiovascular risk factors: from unresolved issues to new
      opportunities.
AB  - With the aim of identifying areas that may deserve some further thinking the
      present review deliberately points out controversial issues in cardiovascular
      research and risk assessment. In the first part of the review general aspects are
      addressed regarding the evaluation of risk factors. A first point of concern is
      the frequent practice of combining different vascular events and effects in
      different vascular beds into a single endpoint. Furthermore, verification of
      vascular events in clinical reality may be surprisingly inaccurate. Problems in
      risk assessment also arise from overlapping properties (shared pathophysiological
      pathways) of traditional risk factors like hypertension, obesity and diabetes. In
      the second part of the review unresolved issues concerning selected established
      and emerging risk factors are discussed. The difficulty of establishing causality
      in cardiovascular disease is addressed, using modification of LDL cholesterol and
      accumulating evidence for pleiotropic effects of the LDL cholesterol-lowering
      statins as an example. As an alternative or supplement to the notion of LDL
      related cardiovascular risk it is proposed to distinguish between statin
      sensitive and statin-insensitive cardiovascular risk. Finally the future
      prospects of selected new and emerging risk factors like CRP, homocysteine,
      asymmetrical dimethylarginine (ADMA), oxLDL, and isoprostanes are evaluated. In
      summary, imprecise terminology and varying definitions of "cardiovascular risk"
      may lead to a considerable blurring of our current risk estimates, which may also
      explain some presently controversial issues. With several new risk factors and
      substantial changes in lifestyle and treatment patterns on the horizon major
      changes in the hierarchy of risk factors may be inevitable.

PMID- 14664898
TI  - Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events. Does
      statin treatment influence plasma ADMA levels?
AB  - The purpose of this study was to evaluate the hypothesis that high serum levels
      of ADMA, an indicator of endothelial dysfunction, are associated with an elevated
      risk of acute coronary events in middle-aged men. To test the hypothesis that
      lipid lowering medication with statins lowers circulating ADMA levels, we also
      investigated the effect of simvastatin and atorvastatin treatment on plasma ADMA
      concentration. In a prospective nested case-control study in 150 middle-aged non
      smoking men from Eastern Finland, those who were in the highest quartile for
      serum ADMA (>0.62 micromol/l) had a 3.9-fold (95% CI: 1.25-12.3, P=0.02) increase
      in risk of acute coronary events compared with other quartiles. In an 8-week
      randomised double-blind placebo-controlled trial, plasma ADMA concentrations
      remained unchanged in simvastatin 80 mg/day (n=16), atorvastatin 40 mg/day (n=16)
      and placebo (n=16) groups over the study period. Our findings indicate that high
      serum levels of ADMA, a potential marker for endothelial dysfunction, may
      increase the risk of acute coronary syndromes. However, aggressive treatment with
      either simvastatin or atorvastatin did not reduce plasma ADMA levels.

PMID- 14664899
TI  - ADMA: a novel risk factor that explains excess cardiovascular event rate in
      patients with end-stage renal disease.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide
      (NO) synthase. By competitively displacing L-arginine from the substrate binding
      site of NO synthase, ADMA interferes with many of the physiological functions of
      NO, like endothelium-dependent vasodilation and leukocyte adhesion. ADMA, like
      its biologically inactive regioisomer, symmetric dimethylarginine (SDMA), can be
      found in human plasma and urine in low concentrations. The concentrations of both
      dimethylarginines are increased in patients with end-stage renal disease, which
      may explain at least in part endothelial dysfunction and cardiovascular
      complications in this patient population. In addition, the metabolism of ADMA,
      but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine
      by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from
      experimental studies suggest that ADMA inhibits vascular NO elaboration at
      concentrations that can be measured in plasma of patients with renal disease.
      Interestingly, ADMA and SDMA are poorly eliminated during hemodialysis. This is
      probably due to a high level of binding of both molecules to plasma proteins.
      High ADMA concentrations in patients with end-stage renal disease may contribute
      to their excess cardiovascular event rate, as in clinical studies a relationship
      between ADMA and carotid artery intimal thickening was found. Moreover, in a
      prospective study we demonstrated recently that determination of ADMA plasma
      concentration is useful to predict future cardiovascular event rate and total
      mortality in this patient population. As other researchers reported observations
      that are in line with our findings, there is evidence that ADMA may be a novel
      cardiovascular risk factor.

PMID- 14664900
TI  - Plasma concentration of asymmetric dimethylarginine and the risk of coronary
      heart disease: rationale and design of the multicenter CARDIAC study.
AB  - There is abundant evidence now that the endothelium plays a crucial role in the
      maintenance of vascular tone and structure. One of the major endothelium-derived
      vasoactive mediators is nitric oxide (NO). Asymmetric dimethylarginine (ADMA) is
      an endogenous inhibitor of NO synthase. ADMA inhibits vascular NO production at
      concentrations found in pathophysiological conditions; ADMA also causes local
      vasoconstriction when it is infused intra-arterially. ADMA is increased in plasma
      of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal
      failure, and chronic heart failure. Increased ADMA levels are associated with
      reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation.
      In several prospective and cross-sectional studies, ADMA evolved as a marker of
      cardiovascular risk in certain populations like hemodialysis patients, non
      smoking men, or intensive-care patients. The CARDIAC study is a multicenter case
      control study designed to address the hypothesis that ADMA may be a suitable and
      sensitive marker of cardiovascular risk in a large, unselected population of both
      sexes, and with a broad range of established cardiovascular risk factors. The
      population included in the CARDIAC study will be prospectively followed for a
      scheduled follow-up period of 4 years, and the data of the CARDIAC-PRO study will
      then provide definite evidence whether ADMA may be prospectively determined as a
      cardiovascular risk factor.

PMID- 14664901
TI  - The DDAH/ADMA/NOS pathway.
AB  - An increasing number of reports in the literature indicate that endogenously
      produced inhibitors of nitric oxide synthase (NOS), particularly asymmetric
      dimethylarginine (ADMA) regulate nitric oxide generation in numerous disease
      states. Two dimethylarginine dimethylaminohydrolase (DDAH) enzymes metabolise
      ADMA. We and others have postulated that activity of DDAH is a key determinant of
      ADMA levels in vivo. This review summarises recent advances in the regulation and
      function of DDAH enzymes and its role in the regulation of nitric oxide
      generation.

PMID- 14664902
TI  - ADMA and oxidative stress.
AB  - Elevated plasma concentrations of the endogenous nitric oxide synthase (eNOS)
      inhibitor asymmetric dimethylarginine (ADMA) represent a novel risk factor for
      the development of endothelial dysfunction and a predictor for all-cause and
      cardiovascular mortality. However, it is unknown whether elevated ADMA plasma
      concentrations may be considered simply as a marker for cardiovascular disease or
      whether increased ADMA levels per se may predispose to the development of
      vascular disease. There is experimental and clinical evidence linking endothelial
      dysfunction to increased production of oxygen-derived free radicals such as
      superoxide anion. Oxidative stress has been shown to increase the activity of
      arginine methylating and ADMA degrading enzymes leading to increased ADMA
      concentrations. Interestingly, the endothelial nitric oxide synthase may become
      uncoupled in the presence of high ADMA levels further contributing to the
      vascular oxidative stress burden. It remains to be established to what extent
      ADMA is able to interact with eNOS in vivo. Possible mechanisms underlying
      increased oxidative stress in the setting of elevated ADMA concentrations and
      therapeutic implications will be discussed.

PMID- 14664903
TI  - NO and angiogenesis.
AB  - Angiogenesis requires the elaboration of endothelium-derived nitric oxide (NO).
      Angiogenic factors induce the release of NO from endothelial cells, which
      mediates a multiplicity of processes involved in angiogenesis. These NO-modulated
      processes include endothelial cell survival, proliferation, migration, and
      interaction with the extracellular matrix. Derangements of the NO synthase
      pathway impair angiogenesis. Accordingly, the competitive inhibitor of the NOS
      pathway asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of
      angiogenesis. By contrast, agents which increase NO synthesis, such as low dose
      statins, enhance angiogenesis. Modulation of the NO synthase pathway could become
      a new therapeutic avenue for angiogenesis-related disorders.

PMID- 14664904
TI  - Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the
      potential role of ADMA.
AB  - Hyperhomocysteinemia is an emerging risk factor for cardiovascular disease and
      stroke. The mechanisms underlying the pathophysiology of hyperhomocysteinemia are
      not completely defined, but endothelial dysfunction resulting from impaired
      bioavailability of nitric oxide is a consistent finding in experimental models.
      One potential mechanism for decreased nitric oxide bioavailability is inhibition
      of endothelial nitric oxide synthase by its endogenous inhibitor, asymmetric
      dimethylarginine (ADMA). Elevated plasma levels of ADMA have been found in
      association with hyperhomocysteinemia and endothelial dysfunction in both animals
      and humans. Additional studies are required to determine the mechanisms by which
      ADMA accumulates in hyperhomocysteinemia and to define the importance of ADMA in
      the endothelial dysfunction of hyperhomocysteinemia in vivo.

PMID- 14664905
TI  - Acetaminophen down-regulates interleukin-1beta-induced nuclear factor-kappaB
      nuclear translocation in a human astrocytic cell line.
AB  - In previous studies performed to elucidate acetaminophen mechanism of action, we
      demonstrated that acetaminophen inhibits prostaglandin E2 production by
      interleukin (IL)-1beta-stimulated T98G human astrocytic cells, without affecting
      cyclooxygenase-2 enzymatic activity. As this result suggests an effect at
      transcriptional level, we examined whether the drug interferes with the
      activation of nuclear factor (NF)-kappaB and STAT3 transcription factors and with
      SAPK signal transducing factor. Western blot analysis of IkappaBalpha protein in
      the cytoplasm of IL-1beta-stimulated T98G cells and electrophoretic mobility
      shift assay (EMSA) on corresponding nuclear extracts indicate that acetaminophen
      (10-1000 microM) dose-dependently inhibits both IkappaBalpha degradation and NF
      kappaB nuclear translocation. In the same cell type neither IL-1beta-dependent
      SAPK activation nor IL-6-induced STAT3 phosphorylation is affected by the drug.
      These data indicate that therapeutic concentrations of acetaminophen induce an
      inhibition of IL-1beta-dependent NF-kappaB nuclear translocation. The selectivity
      of this effect suggests the existence of an acetaminophen specific activity at
      transcriptional level that may be one of the mechanisms through which the drug
      exerts its pharmacological effects.

PMID- 14664906
TI  - Enhanced survival of primary murine dopaminergic neurons induced by a partially
      purified cell lysate fraction from mouse-derived striatal hybrid monoclonal
      cells.
AB  - Lysates of X61, a striatal-derived cell line, and a partially purified
      preparation from the lysate (UF4) contain a factor(s) capable of increasing the
      dopamine content of a mesencephalic-derived dopaminergic cell line (MN9D) and of
      cultures containing primary dopaminergic neurons. Treatment of cultures
      containing dopaminergic primary neurons grown in the absence of target cells over
      a 2 week period with X61 lysate or UF4 resulted in an elevation of dopamine
      levels of the cultures and of media homovanillic acid as well as a 2.0-fold (UF4)
      to 2.9-fold (X61 lysate) increase in the density of dopaminergic neurons in
      treated cultures. The results suggest that the activity factor derived from X61
      is capable of preventing dopaminergic cell loss which occurs in the absence of
      dopaminergic target cells of the corpus striatum.

PMID- 14664907
TI  - Immunohistochemical localization of Notch receptors and their ligands in the
      postnatally developing rat cerebellum.
AB  - Although mRNAs of Notch receptors and their ligands are known to be expressed in
      the postnatally developing rodent cerebellum, their protein localization has been
      poorly investigated. In the present study, we immunohistochemically examined
      localization of Notch receptors and their ligands during postnatal cerebellar
      development in rats. During the first two postnatal weeks, intense signals of
      Notch1-3 were localized in Bergmann fibers (radial fibers of Bergmann glia), as
      confirmed by double fluorescent immunohistochemistry. After that, the signals
      gradually declined into adulthood. Among Notch ligands, Jagged1 and 2 were also
      localized in Bergmann fibers. These results suggest that cell-cell interactions
      through Jagged-Notch signaling can occur between Bergmann glia during postnatal
      cerebellar development.

PMID- 14664908
TI  - Genetically modified human embryonic stem cells relieve symptomatic motor
      behavior in a rat model of Parkinson's disease.
AB  - Embryonic stem (ES) cells have great potential as a cell source for cell
      replacement therapy. To investigate the possibility of using ES cells as a
      carrier of therapeutic gene(s), human ES cells (MB03) were co-transfected with
      cDNAs coding for tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GTPCH I),
      then bulk-selected in the presence of neomycin and hygromycin-B. Successful
      transfection was confirmed by Western immunoblotting and RT-PCR. The genetically
      modified ES cells (bk-THGC) were found to produce a significant amount of L-dopa
      spontaneously and relieved apomorphine-induced asymmetric motor behavior by
      approximately 54% when grafted into striatum of 6-OHDA-denervated rat brain. The
      number of rotations, however, increased up to 176+/-18% in 6 weeks when PBS was
      used instead (sham-graft). Immunohistochemical stainings revealed that the
      grafted human ES cells survived and expressed TH for at least 6 weeks while the
      experiment was continued.

PMID- 14664909
TI  - Spatial learning is delayed and brain-derived neurotrophic factor mRNA expression
      inhibited by administration of MK-801 in rats.
AB  - Brain-derived neurotrophic factor (BDNF) is involved in activity-dependent
      plasticity and interacts with the neurotransmitter glutamate. Glutamate N-methl-D
      aspartate (NMDA) receptor activation increases BDNF expression, while BDNF
      facilitates NMDA activity, with both involved in spatial learning. Administration
      of the NMDA receptor antagonist MK-801 can impair this leaning. The interaction
      between NMDA and BDNF in learning is examined in this study. Adult male Sprague
      Dawley rats received either i.p. MK-801 or saline and were trained to locate a
      submerged water maze platform. Sedentary and activity yoked groups were included
      for biochemical comparisons. Control rats quickly learned the platform location
      while MK-801-treated rats learned at a significantly slower rate (P < 0.0001). In
      situ hybridization for hippocampal BDNF mRNA indicated significant increases in
      the yoked and learning groups. However, MK-801 attenuated the BDNF mRNA increase
      in the learning and activity-yoked conditions (P < 0.05). Administration of MK
      801 to the sedentary group did not alter baseline mRNA levels. These data suggest
      that BDNF expression is important for NMDA-dependent learning and memory.
      Interestingly, learning still occurs across trials independent of the NMDA and
      BDNF interaction. Increases in BDNF and NMDA activity may be significant
      components in learning and memory, and modulation of these systems may be
      beneficial for developing strategies to improve cognitive function.

PMID- 14664910
TI  - Inhibition of staurosporine-induced neuronal cell death by bisphenol A and
      nonylphenol in primary cultured rat hippocampal and cortical neurons.
AB  - We examined whether bisphenol A (BPA) and 4-nonylphenol (NP) influenced
      staurosporine-induced neuronal cell death in primary cultured rat hippocampal and
      cortical neurons. In hippocampal neurons, 17beta-estradiol (E2) (1 nM and 10
      microM) and BPA (10 microM) significantly inhibited the staurosporine-induced
      release of lactate dehydrogenase (LDH). In cortical neurons, BPA significantly
      inhibited the LDH release, while E2 did not. In hippocampal neurons, E2 and BPA
      significantly inhibited the staurosporine-induced increase in caspase-3 activity.
      In cortical neurons, BPA and NP significantly inhibited the increase in caspase-3
      activity, while E2 did not. Furthermore, low-dose BPA (10 nM) also significantly
      inhibited the increase in caspase-3 activity in both hippocampal and cortical
      neurons. BPA and NP might impede normal brain development by inhibiting even
      desirable neuronal cell death, interfering with caspase-3 activation.

PMID- 14664911
TI  - Cytochrome oxidase activity in the monkey globus pallidus and subthalamic nucleus
      after ablation of striatal interneurons expressing substance P receptors.
AB  - To understand functional roles of striatal interneurons in primate basal ganglia
      circuitry, we ablated interneurons expressing substance P (SP) receptors (SPR) in
      the putamen with SP-saporin, a SPR selective neurotoxin. The effect of SP-saporin
      injection into the putamen was evaluated by examining the loss of cholinergic
      interneurons and NADPHd-positive (nicotinamide adenine dinucleotide phosphate
      diaphorase positive) interneurons. We then analyzed regional metabolic changes
      using cytochrome oxidase (CO) histochemistry. CO activity in some regions of the
      internal and external segments of the globus pallidus (GP) in the lesioned
      hemisphere was lower than that in the contralateral or surrounding GP regions. CO
      activity in the subthalamic nucleus, however, showed no significant change. The
      present findings suggest that striatopallidal projection neurons exert enhanced
      inhibitory influence on the GP without modulatory control by the striatal SPR
      expressing interneurons.

PMID- 14664912
TI  - Magnetoencephalography detection of early syntactic processing in humans:
      comparison between L1 speakers and L2 learners of English.
AB  - In previous brain imaging studies of human syntax processing, only phrase
      structure (grammatical category) violations have been shown to elicit a very
      early (approximately 140 ms) neural response. This has led to interpretations
      about the nature of phrase structure encoding in the brain, particularly its
      relationship to early automatic brain processes. Utilizing different sentence
      structures that contrasted within- vs. across-phrase violations, the current
      study examined whether an early response could be elicited by non-phrase
      structure violations. Magnetoencephalography fields were recorded, while both
      first-language speakers (L1) and second-language learners (L2) were tested. A
      prominent syntactic magnetic field component, peaking at around 150 ms post-onset
      (labeled 'SF-M150'), was observed in both hemispheres of only the L1 speakers in
      response to within-phrase violations but not across-phrase violations. The
      results provide evidence that L1 speakers possess the ability for automated
      detection of non-phrase-structure violations, particularly within-phrase
      violations, and that L2 learners may not have sufficient neural representation
      available for an early automated response to the target violations.

PMID- 14664913
TI  - The auditory N1m reveals the left-hemispheric representation of vowel identity in
      humans.
AB  - The cortical correlates of the perception of the sustained vowels /a/, /o/ and
      /u/ were studied by using whole-head magnetoencephalography (MEG). The three
      vowels which were located on a line in the space spanned by the first (F1) and
      second (F2) formants and having equal F2-F1 differences evoked equally strong
      auditory N1m responses at 120 ms after stimulus onset. The left-hemispheric
      distribution of the source locations, estimated by equivalent current dipoles,
      reflected the acoustic similarity of the vowels: the growing distance of the
      vowels in the F2,F1-space was accompanied by a growing distance between the
      centres of gravity of activation elicited by each vowel. Thus, direct evidence
      for the orderly left-hemispheric representation of phonemes in human auditory
      cortex was found.

PMID- 14664914
TI  - Synergism between tumor necrosis factor-alpha and H2O2 enhances cell damage in
      rat PC12 cells.
AB  - Tumor necrosis factor-alpha (TNFalpha) is harmful in the early phase and
      beneficial in the long-term phase after brain injury. Reactive oxygen species
      (ROS) are among the most toxic mediators activated by injury. We speculate that
      part of the TNFalpha toxicity is mediated by its synergism with ROS. Thus,
      toxicity of TNFalpha and ROS, alone or together, were studied in PC12 cells. PC12
      cells were exposed for 18 h to TNFalpha (0-100 ng/ml), to H2O2 (1-300 microM) or
      to both, each at sub-toxic concentrations. Lactic dehydrogenase release,
      prostaglandin E2 accumulation and morphology indicated cell death and stress
      response. TNFalpha toxicity was seen at >50 ng/ml, and that of H2O2 at >150
      microM, however, when together, sub-lethal levels (25 ng/ml TNFalpha and 30
      microM H2O2) induced toxicity. Dexanabinol, an N-methyl-D-aspartate antagonist
      with antioxidant and anti-TNFalpha properties, completely rescued the cells.
      These findings corroborate our hypothesis on the cooperative toxicity exerted by
      TNFalpha and ROS after brain injury.

PMID- 14664915
TI  - Electrophysiological effects of melanocortin receptor ligands on neuronal
      activities of monoaminergic neurons in rats.
AB  - The melanocortin-4 (MC4) receptor may possibly be involved in stress and stress
      related behavior. In the present study, we examined effects of an
      intracerebroventricular injection of the MC4 receptor agonist, Ac-[Nle4,Asp5,D
      Phe7,Lys10]-alpha-MSH 4-10-NH2 (MT II), and the MC4 receptor inverse agonist,
      Agouti-related protein (AGRP), on dorsal raphe nucleus (DRN) serotonergic neurons
      and the locus coeruleus (LC) noradrenergic neurons, both of which are brain
      neuronal systems related to responses to stress. The firing rate of DRN
      serotonergic neurons was increased by MTII, while AGRP had a lack of effect on
      the firing rate of DRN serotonergic neurons. In comparison with the DRN, MTII
      significantly reduced the firing rate of LC noradrenergic neurons, while AGRP
      increased LC neuronal activity. These findings suggest that MC4 receptor ligands
      differently regulate serotonergic and noradrenergic neuronal systems. The MC4
      receptor mediating multiple regulation on the monoaminergic neuronal system may,
      in part, relate to stress responses (anxiety and/or depressive behavior).

PMID- 14664916
TI  - Somatotropic-axis deficiency affects brain substrates of selective attention in
      childhood-onset growth hormone deficient patients.
AB  - Reduced levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      are associated with deteriorated cognitive performance in senescence. Little work
      has been done on the effect of GH and IGF-1 on a crucial aspect of cognition,
      selective attention. This study investigated the effect of GH/IGF-1 on
      performance and brain potentials (EEG) during a selective-attention task in
      patients with low levels of GH and IGF-1 (childhood-onset growth hormone
      deficiency) compared to healthy controls. Detection of occasional visual target
      patterns was impaired in patients. This was paralleled by a reduction in an
      attention-related brain potential, which has been associated previously with
      anterior cingulate cortex functioning.

PMID- 14664917
TI  - Effects of stress and etifoxine on pentobarbital-induced loss of righting reflex
      in Balb/cByJ and C57BL/6J mice.
AB  - We hypothesized that functional changes in the GABAergic system induced by stress
      would differ between two inbred mouse strains BALB/cByJ and C57BL/6J. We compared
      the effects of restraint stress and of the anxiolytic drug etifoxine (EFX) on the
      duration of pentobarbital-induced loss of righting reflex (hypnotic effect) in
      the two strains. Naive BALB/cByJ mice were less sensitive than naive C57BL/6J
      mice to the hypnotic effect of pentobarbital. C57BL/6J mice exhibited a
      shortening in the duration of pentobarbital-induced hypnosis following stress
      whereas stress had no effect in BALB/cByJ mice. EFX reversed the shortening of
      pentobarbital-induced hypnosis elicited by stress in C57BL/6J and shortened the
      duration of pentobarbital-induced hypnosis after stress in BALB/cByJ mice.
      Alterations in the GABAergic function in BALB/cByJ mice could be corrected by
      EFX, an enhancer of GABAergic transmission.

PMID- 14664918
TI  - Immunohistochemical analysis of myelination following hemicranial irradiation in
      neonatal rats.
AB  - The mechanism of radiation-induced diffuse brain injury was investigated in a
      neonatal rat hemicranial irradiation model using immunohistochemistry. Neonatal
      Fischer 344 rats received hemicranial irradiation with a single dose of 15 Gy,
      and appropriate combinations of myelin markers were used to assess the myelin
      damage at various stages of myelin development. Antibodies against myelin basic
      protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin oligodendrocyte
      glycoprotein were used, and the density of the antibody-positive fibers was
      classified into five categories. Statistical analysis showed significant
      differences between irradiated and unirradiated hemispheres. The differences
      decreased and myelination approached normality by postnatal day 70. These results
      show that myelination in the neonatal rat can recover from the developmental
      delay caused by a single 15 Gy dose of hemicranial irradiation.

PMID- 14664919
TI  - Identification of a novel amino-terminal fragment of amyloid precursor protein in
      mouse neuroblastoma Neuro2a cell.
AB  - The amyloid precursor protein (APP) can be catabolized mainly via either an
      amyloidogenic or non-amyloidogenic pathway, leading to the production of amyloid
      beta (Abeta) or the secreted form of APP (sAPP), respectively. Abeta is a major
      component of deposits found in Alzheimer's disease brains and plays an important
      role in the pathogenesis of this disease, whereas sAPP (though it might have some
      neurotropic function) has a largely unknown function and metabolism. In this
      study, a novel 11-kDa APP amino-terminal fragment from Neuro2a cells (but also
      present in primary cultured neurons, glias, and mouse cerebral cortex) was
      characterized using mass spectrometric and amino acid sequence analyzes. We could
      not detect the fragment extracellularly, and suggest that it was generated in a
      non-secretory, acidic degradation pathway. As this is a fragment of sAPP, it is
      possible that inhibition of this pathway increases amount of sAPP and results in
      neuroprotection.

PMID- 14664920
TI  - Effects of pentobarbital on GABA-activated currents in acutely-isolated rat
      dentate gyrus granule neurons.
AB  - Granule neurons from the rat dentate gyrus were acutely isolated and whole-cell
      currents recorded. Maximal enhancement of 7 microM gamma-aminobutyric acid (GABA;
      EC30) evoked currents was obtained with 100 microM pentobarbital where the peak
      current was 2.1+/-0.2 of control. One hundred microM pentobarbital alone evoked
      no current response whereas 1 mM pentobarbital elicited a current response that
      was 0.4+/-0.2 of the 100 microM GABA-activated peak current. In 100 microM
      pentobarbital, the GABA EC50 value shifted from 14 to 3 microM but the peak
      saturating-current value was not altered. An off-current was recorded on removal
      of 100 microM and higher pentobarbital concentrations. Ten mM pentobarbital
      abolished the peak-current response to 7 and 100 microM GABA. The results show
      that in the granule neurons the drug potency differs for the different effects of
      pentobarbital at GABAA receptors with the modulatory and inhibitory effects
      requiring lower concentrations than the direct activation of the receptors.

PMID- 14664921
TI  - Structural involvement of the glutamatergic presynaptic boutons in a transgenic
      mouse model expressing early onset amyloid pathology.
AB  - While the cholinergic depletion in Alzheimer's disease (AD) has been known for
      some time, a definitive involvement of other neurotransmitter systems has been
      somewhat more elusive. Our study demonstrates a clear involvement of both
      glutamatergic and, to a lesser extent, GABAergic neurons in an early onset
      transgenic mouse model of AD-like amyloid pathology. Immunohistochemical staining
      and subsequent quantification has revealed a statistically significant increased
      density of glutamatergic and GABAergic presynaptic boutons in both the plaque
      free and plaque adjacent cortical neuropile areas of transgenic mice as compared
      to non-transgenic controls. Furthermore, amyloid plaque size was shown to have a
      statistically significant effect on the relative area occupied by dystrophic
      glutamatergic neurites in the peri-plaque neuropile. These findings support our
      hypothesis that the amyloid pathology progresses in a time and neurotransmitter
      specific manner, first in the cholinergic system which appears to be most
      vulnerable, followed by the glutamatergic presynaptic boutons and finally the
      somewhat more resilient GABAergic terminals.

PMID- 14664922
TI  - Different mechanisms of hypoxic injury on white matter and gray matter as
      revealed by dynamic changes in glucose metabolism in rats.
AB  - Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose
      ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and the
      fractional rate constant (=k3*) of [18F]FDG proportional to the cerebral glucose
      metabolic rate in white matter and gray matter was investigated with positron
      autoradiography. In both white matter and gray matter, the k3* value with > or =
      20 min hypoxia was markedly lower than the unloaded control value, indicating
      irreversible hypoxic injury. Next, the neuroprotective effect against hypoxia
      induced by the addition of an N-methyl-D-aspartate receptor antagonist or a free
      radical scavenger was assessed by determining whether a decrease in the k3* value
      after hypoxia loading was prevented. In gray matter, both agents exhibited a
      neuroprotective effect against 20 min hypoxia. In white matter, however, only the
      free radical scavenger was effective. These results suggest a similarity in the
      degree of vulnerability to hypoxia between white matter and gray matter as well
      as a difference in the developmental mechanism of hypoxic injury, i.e. the
      involvement of both glutamate and free radicals in gray matter, and the more
      selective involvement of free radicals in white matter.

PMID- 14664923
TI  - No replication of the association between the Nicastrin gene and familial early
      onset Alzheimer's disease.
AB  - Polymorphisms in the Nicastrin (NCSTN) gene have recently been associated with
      familial early-onset Alzheimer's disease (AD). The authors genotyped four NCTSN
      polymorphisms in a large cohort of 489 AD cases (including 158 sporadic early
      onset AD cases and 95 familial early-onset AD cases) and 386 controls but failed
      to replicate the association between NCSTN haplotype B and AD.

PMID- 14665333
TI  - [Introduction].

PMID- 14665334
TI  - [Medical selection of blood donors: risk prevention for the recipient].

PMID- 14665335
TI  - [Medical selection of blood donors: risk prevention for the donor].

PMID- 14665336
TI  - [Medical selection of blood donors: biology].

PMID- 14665337
TI  - [Medical selection of blood donors: specificities of the autologous transfusion].

PMID- 14665338
TI  - Do unto others--why I would want anesthesia for my prostate biopsy.

PMID- 14665339
TI  - Prostatitis, interstitial cystitis, chronic pelvic pain, and urethral syndrome
      share a common pathophysiology: lower urinary dysfunctional epithelium and
      potassium recycling.

PMID- 14665340
TI  - Laparoscopic appreciation of perirenal attachments.

PMID- 14665341
TI  - Sensitivity of chest fluoroscopy compared with chest CT and chest radiography for
      diagnosing hydropneumothorax in association with percutaneous nephrostolithotomy.
AB  - OBJECTIVES: Hydropneumothorax (HPTX) is recognized as a potential complication of
      percutaneous nephrostolithotomy (PCNL), particularly with supracostal access.
      Postoperative chest radiography (CXR) is routinely used to evaluate the chest
      after PCNL. We prospectively compared the sensitivity of intraoperative chest
      fluoroscopy with immediate postoperative portable CXR and postoperative day 1
      chest computed tomography (CT) for the detection of pleural fluid. METHODS: A
      total of 89 consecutive patients (mean age 47.9 +/- 13.3 years; 100 renal units)
      undergoing PCNL were prospectively evaluated with intraoperative fluoroscopy at
      the conclusion of the procedure and then with anteroposterior CXR in the
      postanesthesia care unit and postoperative day 1 noncontrast, thin-cut CT of the
      kidneys and lung bases. CT imaging of the lung bases comprised the reference
      standard for detecting pleural fluid. RESULTS: A total of 104 percutaneous renal
      accesses in 100 renal units, 60 above and 44 below the 12th rib, were used. In 16
      cases (16%), a second-stage procedure was performed to clear residual stone
      fragments detected on post-PCNL CT. HPTX was detected in 1, 8, and 38 cases by
      initial fluoroscopy, immediate postoperative CXR, and CT scan, respectively.
      Intervention was necessary in 7 patients. In 2 patients with fluoroscopic
      evidence of pleural fluid (1 at the initial PCNL and 1 during second-look
      flexible nephroscopy), intraoperative pleural drainage was performed
      percutaneously. In the other 5 patients, intervention was determined by the size
      of the HPTX on chest CT scan (n = 1) or the presence of symptoms (n = 4). In no
      case was intervention performed on the basis of the immediate postoperative CXR
      findings when intraoperative chest fluoroscopy was negative. CONCLUSIONS:
      Intraoperative chest fluoroscopy during PCNL is sufficient to detect clinically
      significant HPTXs, and, therefore, routine postoperative CXRs are not necessary.
      However, a high index of suspicion based on clinical symptoms postoperatively
      should prompt chest imaging.

PMID- 14665342
TI  - Benign retroperitoneal schwannoma: a case series and review of the literature.
AB  - OBJECTIVES: To present our experience with four retroperitoneal schwannomas
      treated by surgical excision and review the current literature. Retroperitoneal
      schwannomas are rare, benign tumors and infrequently present to the urologist.
      METHODS: From 1997 through 2002, the charts of 164 patients with a diagnosis of
      benign retroperitoneal soft tissue mass were reviewed. Of those, four had a
      pathologic diagnosis of retroperitoneal schwannoma. RESULTS: Three of the 4
      patients were women, with a median age of 54 years (range 46 to 80). The average
      tumor size was 13.7 cm (range 8.8 to 20). All patients underwent magnetic
      resonance imaging, computed tomography, or ultrasonography, and 3 of the 4
      patients underwent a computed tomography-guided fine needle aspiration biopsy
      (all were either inaccurate or inconclusive). All patients underwent complete
      tumor excision with free margins of resection and tolerated surgery without any
      complications. None of the patients have had any evidence of recurrence at a mean
      follow-up of 26 months (range 10 to 48). CONCLUSIONS: Retroperitoneal schwannomas
      are difficult to diagnose preoperatively. Computed tomography-guided fine needle
      aspiration biopsy does not appear to provide an accurate preoperative diagnosis.
      The surgical approach should focus on complete excision of the mass. Patients
      undergoing complete surgical resection tend to do well without evidence of early
      recurrence.

PMID- 14665343
TI  - Ileal ureter substitution: a contemporary series.
AB  - OBJECTIVES: To review our contemporary experience with ileal ureter
      reconstruction. Despite advancements in surgical technology and technical
      expertise, ureteral injuries continue to occur. These injuries can be extensive,
      and ileal ureter reconstruction may be necessary. METHODS: A total of 18 ileal
      ureter substitutions were performed in 16 adults (10 men and 6 women) by a single
      surgeon during a 6-year period. The mean patient age was 49.4 years (range 25 to
      72). The mean follow-up was 18.6 months (range 7 to 59). All ileal ureter
      substitutions were performed in an isoperistaltic, refluxing fashion. Follow-up
      included clinical evaluation, nuclear renography, intravenous urography, and
      serum chemistry testing. RESULTS: Postoperative nuclear renography demonstrated
      no relative loss of function of the affected renal unit and no evidence of
      functional obstruction. An unobstructed state was also confirmed with intravenous
      urography. No statistically significant metabolic changes were found in any
      patient, as assessed by serum chemistry testing. None of the patients had
      evidence of new stone formation. Two patients developed an isolated, symptomatic
      urinary tract infection during follow-up, and one has had recurrent urinary tract
      infections, a problem that was present preoperatively. CONCLUSIONS: Ileal ureter
      substitution remains an effective treatment for patients with complex ureteral
      strictures or injuries. Stone activity does not appear to increase, and metabolic
      sequelae are uncommon in properly selected patients.

PMID- 14665344
TI  - Kidney transplantation from living-unrelated donors: comparison of outcome with
      living-related and cadaveric transplants under current immunosuppressive
      protocols.
AB  - OBJECTIVES: Living-unrelated donors may become an additional organ source for
      patients on the kidney waiting list. We studied the impact of a combination of
      calcineurin inhibitors and mycophenolate-mofetil together with steroids on the
      outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation.
      METHODS: Between September 1997 and January 2000, 129 patients underwent LRD (n =
      80) or LUR (n = 49) kidney transplantation, and another 173 patients received a
      cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil
      with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the
      patient and graft survival data, rejection rate, and graft functional parameters.
      RESULTS: LRD recipients were younger (33.6 years) than LUR (47.8 years) and
      cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD
      patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of
      LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The
      creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70
      mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68,
      and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively.
      No difference in patient survival rates was found among the groups. The 1, 2, and
      3-year graft survival rates were significantly better in recipients of LRD
      (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and
      87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%,
      respectively; P <0.01). CONCLUSIONS: Despite HLA disparity, the rejection and
      survival rates of LUR transplants under current immunosuppressive protocols are
      comparable to those of LRD and better than those of cadaveric transplants.

PMID- 14665345
TI  - Practice patterns among urologic surgeons treating localized renal cell carcinoma
      in the laparoscopic age: technology versus oncology.
AB  - OBJECTIVES: To evaluate the effect of laparoscopy on practice patterns at a
      single institution in the treatment of renal cell carcinoma. Many now regard
      laparoscopic radical nephrectomy (LRN) as a standard of care in the management of
      localized renal cell carcinoma. As laparoscopy becomes more prevalent in the
      urologic community, practice patterns are changing. METHODS: We analyzed the
      renal cancer surgical database at the Weill Medical College of Cornell University
      from 1997 to 2002. We compared three groups, including open radical nephrectomy
      (ORN), open partial nephrectomy (OPN), and LRN. RESULTS: A total of 222
      consecutive renal surgeries done for presumed malignancy were performed from 1997
      to 2002. A total of 194 were assessable. Of these, 63 were OPNs, 51 were ORNs,
      and 80 were LRNs. When analyzed over time, during the latter half of 2000, 89% of
      all LRNs were performed on tumors less than 4 cm in size. More recently, in 2002,
      only 42% of LRNs were performed for tumors 4 cm or less in size. From 1997 to
      2000, 30% of all OPNs were done on tumors greater than 4 cm compared with 28%
      from 2000 to 2002. Of 30 OPNs performed from 1997 to 2000, 21 (70%) were
      performed on small (4 cm or less) tumors compared with 24 (73%) of 33 from 2000
      to 2002. CONCLUSIONS: From 2000 to 2002, the percentage of tumors less than 4 cm
      that were treated with LRN has increased with time. In the ORN cohort, the
      percentage of nephrectomies performed on small tumors (less than 4 cm) has
      decreased with time, and the trends in the OPN group have remained relatively
      stable. As an institution becomes more comfortable with laparoscopic techniques,
      technological concerns are likely to play less of a role in determining treatment
      algorithms among treating urologists.

PMID- 14665346
TI  - Racial disparity in incidence patterns and outcome of kidney cancer.
AB  - OBJECTIVES: To identify the subgroups that primarily contribute to the greater
      incidence and mortality of renal cancer in black Americans compared with white
      Americans. METHODS: We analyzed age, stage, and race-related differences in the
      incidence and survival among patients with renal cancer using the national
      Surveillance, Epidemiology, and End Results (SEER) registry database. White and
      black patients with renal cell carcinoma who were older than 19 years of age and
      had been diagnosed between 1975 and 1998 were included. Incidence trends were
      analyzed by joinpoint regression with the statistical significance level at P
      <0.05. The Cox proportional hazards model was used to determine the overall
      survival of patients with renal cell carcinoma by race (white versus black), age
      (20 to 59 versus 60+ years), and stage (local versus regional/distant). RESULTS:
      Localized disease predominantly accounted for the rise in incidence. Both black
      age groups with localized disease had a greater estimated annual percentage of
      incidence increase (4.46% for 20 to 59 years and 4.35% for 60+ years) compared
      with their white counterparts (2.87% and 3.06%, respectively). The magnitude of
      survival difference was largest between black versus white patients younger than
      60 years of age who had local stage disease, with a median survival time of 190
      and 259 months, respectively (P <0.0001). CONCLUSIONS: Young black patients with
      localized renal cancer appear to have had a greater rise in incidence and a
      poorer outcome than white patients of the same age and disease stage. Additional
      investigation is warranted to define the role of these race, stage, and age
      related disparities in the etiology, prognosis, treatment, and follow-up of
      kidney cancer.

PMID- 14665347
TI  - Long-term outcome of laparoscopic radical nephrectomy for pathologic T1 renal
      cell carcinoma.
AB  - OBJECTIVES: To evaluate the oncologic adequacy of laparoscopic radical
      nephrectomy in patients with pathologic Stage T1 renal cell carcinoma, we
      analyzed the long-term results in those treated with laparoscopy and those
      undergoing open surgery. METHODS: The renal tumor of 263 patients was confirmed
      to be Stage T1 by pathologic examination of the radical nephrectomy specimen
      between January 1992 and June 2002. Of the 263 patients, 195 were treated
      laparoscopically and the remaining 68 by open surgery. The patient follow-up
      lasted until July 31, 2002. RESULTS: The follow-up period of the laparoscopy
      group was 2 to 121 months (median 40). A total of 183 patients survived, 5 died
      of renal cancer, 7 died without any recurrent disease, and 7 were lost to follow
      up. Seeding of the port sites did not develop in any of the patients. Ten
      patients had metastatic or recurrent disease within 3 to 110 months, and 5 of
      these patients died of cancer within 12 to 86 months. The 5-year disease-free and
      patient survival rate was 91%, and 94%, respectively. The 68 patients who
      underwent open surgery were followed up for 11 to 126 months (median 65). Of the
      68 patients, 56 survived without any recurrent disease, 4 survived with
      metastasis, 6 died of metastatic disease within 8 to 49 months, and 6 were lost
      to follow-up. The 5-year disease-free and patient survival rate was 87% and 94%,
      respectively. CONCLUSIONS: Laparoscopic radical nephrectomy is an alternative
      technique with comparable oncologic results to open nephrectomy in patients with
      localized pathologic Stage T1 renal cell carcinoma.

PMID- 14665349
TI  - Long-term follow-up after transurethral resection of the prostate, contact laser
      prostatectomy, and electrovaporization.
AB  - OBJECTIVES: To compare the long-term results of subjective changes, flowmetry,
      morbidity, and mortality after transurethral resection of the prostate, contact
      laser prostatectomy, and electrovaporization in men with lower urinary tract
      symptoms associated with benign prostatic hyperplasia. METHODS: A prospective
      randomized controlled trial was conducted. Included in the study were men with
      lower urinary tract symptoms, who met the criteria of the International
      Scientific Committee on Benign Prostatic Hyperplasia, had a prostate volume
      between 20 and 65 cm(3), and a Schafer obstruction grade of 2 or greater. The
      subjective changes were quantified using the International Prostate Symptom
      Score, Symptom Problem Index, quality-of-life question, and benign prostatic
      hyperplasia impact index. Morbidity was registered objectively and by patient
      questionnaire. Maximal flow was measured by free uroflowmetry. These parameters
      were measured at regular intervals for up to 1 year. At the end of 2002, all
      patients were invited for a long-term follow-up examination, including the
      aforementioned parameters. RESULTS: Fifty men were randomized to undergo
      transurethral resection of the prostate, 45 laser treatment, and 46
      electrovaporization. Of the 50 men, 70% were followed up for a maximum of 7
      years. The values for the International Prostate Symptom Score, Symptom Problem
      Index, quality-of-life score, and benign prostatic hyperplasia impact index
      increased slightly after a mean follow-up of 4.3 years. The maximal uroflow
      decreased similarly in all treatment groups to about 150% of the preoperative
      values. Morbidity, reoperation rates, and mortality were also similar.
      CONCLUSIONS: This study, with up to 7 years of follow-up, demonstrated durable
      subjective and objective results for patients with lower urinary tract symptoms
      associated with benign prostatic hyperplasia after transurethral resection of the
      prostate, contact laser prostatectomy, or electrovaporization. No clinically
      relevant differences were found among these modalities.

PMID- 14665348
TI  - Impact of tumor-associated symptoms on the prognosis of patients with renal cell
      carcinoma: a single-center experience of 683 patients.
AB  - OBJECTIVES: To evaluate the impact of cancer-associated symptoms present at the
      diagnosis of renal cell carcinoma (RCC) on the prognosis of patients. Increasing
      numbers of RCC are currently detected incidentally by routine ultrasonography.
      METHODS: From January 1994 to December 2000, 693 operations for RCC in 683
      consecutive patients have been performed at our institution. Overall, tumor
      specific, and progression-free survival were investigated using the Kaplan-Meier
      method. For multivariate analysis regarding tumor-specific survival, the Cox
      regression model, including risk ratios, was used. A receiver operating
      characteristics curve regarding the sensitivity and specificity for the
      association between tumor size and symptoms was used. RESULTS: Of the 683
      patients, 417 patients were male and 266 female. The mean patient age was 62
      years (range 16 to 88). Of the 683 patients, 141 (20.8%) presented with symptoms
      suspicious for cancer. The 5-year overall, progression-free, and cancer-specific
      survival rates were 82%, 79%, and 86%, respectively, for asymptomatic patients
      compared with 60%, 55%, and 65%, respectively, for patients with symptoms at
      diagnosis (P <0.0001, log-rank test). The cutoff value of 5 cm for the tumor
      diameter to result in symptoms was chosen on the receiver operating
      characteristic curve. Multivariate analysis found tumor grade (P = 0.001), tumor
      stage (P = 0.001), presence of symptoms (P = 0.013), and tumor diameter (P =
      0.005) to be independent prognostic parameters for cancer-specific survival.
      CONCLUSIONS: Tumors larger than 5 cm were significantly more likely to cause
      symptoms compared with smaller tumors in our series. In multivariate analysis,
      patients presenting with symptoms suspicious for cancer at the diagnosis of RCC
      had a 1.8-fold greater risk of dying of cancer compared with patients without
      symptoms.

PMID- 14665350
TI  - Impact of patient educational level on treatment for patients with prostate
      cancer: data from CaPSURE.
AB  - OBJECTIVES: To examine the effect of a patient's educational level on treatment
      selection for patients with newly diagnosed prostate cancer. A patient's
      educational level may impact a patient's understanding and perception of the
      risks and benefits of the treatment options for prostate cancer. METHODS: We
      examined 3484 patients in CaPSURE with prostate cancer between 1992 and 2001. Chi
      square and multinomial logistic regression analyses were performed to determine
      the role of education level in primary treatment received relative to other
      pretreatment predictors (age, race, insurance status, prostate cancer risk,
      comorbidity). Prostate cancer risk stratification was determined by serum
      prostate-specific antigen level and tumor stage and grade. RESULTS: The mean
      patient age was 67.7 +/- 8.3 years, and the mean prostate-specific antigen level
      was 13.0 +/- 18.7 ng/mL. Of the 3484 patients, 16.7% had less than a high school
      education, 27.0% had completed high school or technical school, 19.5% had had
      some college, 18.0% had graduated from college, and 18.6% had had some graduate
      education. In bivariate analysis, the factors predictive of treatment selection
      were patient age, race, education, insurance status, risk group, and patient
      comorbidity (all P <0.001). In multinomial regression analysis, the factors
      predicting treatment received were age, race, cancer risk group, and comorbidity.
      For patients older than 75 years, those with a higher education level received
      more aggressive treatment (radiotherapy versus hormonal therapy) than did those
      with less education. CONCLUSIONS: Patient age, race, cancer risk group,
      comorbidity, and, for men older than 75 years, education level are the factors
      predictive of the primary treatment received by men with newly diagnosed prostate
      cancer.

PMID- 14665351
TI  - Epidemiology of prostate cancer in the Umbria region of Italy: evidence of
      opportunistic screening effects.
AB  - OBJECTIVES: To examine the impact of prostate-specific antigen-based screening on
      prostate cancer incidence, mortality, and survival in the Umbria region of Italy
      for the period 1978 to 1999. METHODS: Incidence rates were derived from an ad hoc
      survey and from cancer registry records for the period 1978 to 1982 and 1994 to
      1999, respectively. The mortality trend was assessed by joinpoint analysis using
      data from the official publications. The observed, relative, and age-adjusted
      relative survival rates were also calculated. RESULTS: The number of newly
      diagnosed cases in 1997 to 1999 was almost four times greater than in 1978 to
      1982, the crude incidence rate was more than three times, and the age-adjusted
      incidence rate increased by about 125%. No trend was apparent for mortality. The
      survival rates also showed a large increase. The 5-year relative survival rate
      was 37% and 74% for 1978 to 1982 and 1994 to 1998 incident cases, respectively.
      People older than 75 years showed the same striking increase in incidence and
      survival rates as the younger age groups. CONCLUSIONS: As in many other developed
      countries, prostate cancer screening activities are the likely cause of the
      increase in incidence and survival rates observed in the study area, but a
      decreasing mortality trend is not yet evident. Opportunistic screening is likely
      to be performed among all age groups, including the elderly, although the latter
      are unlikely to benefit from intervention. The evaluation of opportunistic
      screening is difficult and a lack of evaluation implies a high risk of
      ineffective interventions and inequality of care.

PMID- 14665352
TI  - Evidence of increased prostate cancer detection in men aged 50 to 59: a review of
      324,684 biopsies performed between 1995 and 2002.
AB  - OBJECTIVES: To analyze the age-specific detection rate of prostate cancer
      diagnosed from 324,684 biopsies submitted to a single laboratory and to assess
      the degree of prostate cancer in younger men. The advent of prostate-specific
      antigen (PSA) testing and increased prostate cancer screening has led to
      increased evaluations for prostate cancer. The initial stage and age at
      presentation in prostate cancer has shifted. METHODS: From 1995 through 2001, all
      prostate biopsies submitted to the laboratory were reviewed and analyzed for the
      diagnosis of prostate cancer, cancer detection rate, and age at diagnosis.
      RESULTS: The overall detection rate of prostate cancer increased by 15% from 29%
      to 34% for all biopsies submitted during the study period. For the age group 50
      to 59 years, a 45% increase occurred in the detection of prostate cancer from a
      baseline of approximately 11% in 1995 to greater than 16% in 2001. For the age
      group 70 to 79 years, the detection of prostate cancer decreased from a baseline
      of 41% in 1995 to 36% in 2001. CONCLUSIONS: The increase in prostate cancer
      diagnosis among younger men in the United States has been significant. The
      increase is likely multifactorial and may be attributable to the impact of PSA
      and prostate cancer screening efforts. This has led to a greater number of
      younger men undergoing evaluation for prostate cancer. Thus, a heightened
      awareness regarding the diagnosis of prostate cancer among younger men is needed.

PMID- 14665353
TI  - Voiding impairment after prostate biopsy: does tamsulosin treatment before biopsy
      decrease this morbidity?
AB  - OBJECTIVES: To evaluate the association of transrectal ultrasound (TRUS)-guided
      prostate biopsy with voiding impairment and to investigate whether tamsulosin
      treatment given before prostate biopsy could improve voiding impairment after the
      procedure. METHODS: The study included 66 consecutive patients who underwent TRUS
      guided 12-core prostate biopsy and were prospectively randomized. Of the
      patients, 33 were treated with tamsulosin (0.4 mg daily) beginning the day before
      the biopsy procedure for 30 days. The remaining 33 patients underwent TRUS-guided
      prostate biopsy only with no tamsulosin treatment and served as the control
      group. The International Prostate Symptom Score (IPSS) and maximal flow rate
      (Qmax) were recorded in all patients before the procedure and on postbiopsy days
      7 and 30. All patients were followed up and questioned about difficulty voiding
      and acute urinary retention after the procedure. RESULTS: No difference was found
      in the mean IPSS and Qmax before biopsy between the two groups (P >0.05). Acute
      urinary retention after the biopsy procedure developed in 1 patient in the
      tamsulosin group and 3 patients in the control group. The rate of voiding
      difficulty on postprocedure day 7 was significantly lower in the tamsulosin group
      (9.09%) than in the control group (42.42%), a statistically significant
      difference (P <0.001). In the tamsulosin group, the IPSS was significantly
      decreased on postbiopsy days 7 and 30 compared with the baseline value (P <0.05
      and P <0.001, respectively), and Qmax was significantly elevated on postbiopsy
      day 30 (P <0.01). In the control group, the IPSS was significantly greater (P
      <0.05) and the Qmax was significantly lower (P <0.001) on postbiopsy day 7
      compared with the baseline value. CONCLUSIONS: The results of our study show that
      TRUS-guided prostate biopsy leads to transient voiding impairment, and therefore,
      the alpha(1)-blocker tamsulosin before biopsy and for a brief interval afterward
      may decrease this morbidity.

PMID- 14665354
TI  - A randomized double-blind prospective study evaluating patient tolerance of
      transrectal ultrasound-guided biopsy of the prostate using prebiopsy rofecoxib.
AB  - OBJECTIVES: To assess the use of a prebiopsy outpatient analgesia using the
      nonsteroidal anti-inflammatory agent rofecoxib (Vioxx). Urologists perform
      approximately 500,000 transrectal ultrasound (TRUS)-guided biopsies of the
      prostate per year, commonly without analgesia. Recent reports, however, have
      determined that a significant proportion of patients undergoing TRUS-guided
      biopsies have pain. METHODS: We performed a prospective randomized double-blind
      study of 56 men referred for TRUS biopsy of the prostate. They were randomly
      assigned to receive 50 mg of oral rofecoxib or placebo before TRUS biopsy. After
      the biopsies, the patients were asked to score the severity of pain by filling
      out a visual analog pain scale. At the end of 1 week, all patients were asked to
      mail in a questionnaire regarding the morbidity of the prostate biopsy, including
      dysuria, hematuria, urinary retention, postbiopsy fever, and rectal bleeding.
      Analysis was completed to assess whether rofecoxib decreased the patients'
      perception of pain. The postbiopsy morbidity of patients receiving placebo versus
      rofecoxib was compared. RESULTS: Thirty-seven percent of patients receiving
      placebo and 42% of patients receiving rofecoxib had significant pain (5 or
      greater on the visual analog pain scale). The median pain score of patients
      receiving rofecoxib (4.0) versus placebo (4.0) was not significantly different
      statistically (P = 0.3139) using a Wilcoxon rank sum analysis. The incidence of
      postbiopsy morbidity was not different. CONCLUSIONS: Our results confirm the
      findings of previous studies demonstrating that a significant proportion of
      patients undergoing prostate biopsies have pain. More importantly, we found that
      prebiopsy rofecoxib did not significantly decrease the patients' severity of
      discomfort. Finally, the morbidity after biopsy was not increased with the use of
      rofecoxib.

PMID- 14665355
TI  - Volume indexes of total, free, and complexed prostate-specific antigen enhance
      prediction of extraprostatic disease extension in men with nonpalpable prostate
      cancer.
AB  - OBJECTIVES: To analyze the ability of volume-adjusted total, complexed, and free
      prostate-specific antigen (PSA) to predict organ-confined cancer at radical
      prostatectomy in patients with nonpalpable disease. METHODS: Collected sera were
      assayed for total PSA (tPSA), complexed PSA (cPSA), and free PSA (fPSA) in 78 men
      who underwent radical prostatectomy with nonpalpable prostate cancer. The
      pathologic results (organ-confined versus extraprostatic extension [EPE]), tPSA,
      cPSA, fPSA/tPSA ratio, cPSA/tPSA ratio, fPSA/cPSA ratio, tPSA density (tPSAD),
      cPSA density (cPSAD), and fPSA density (fPSAD) were compared by the Mann-Whitney
      U test and receiver operating characteristic curves. RESULTS: Fifteen men (19.2%)
      had pathologic EPE. After stratifying the patients on the basis of the Beckman
      tPSA, the cPSAD, tPSAD, and fPSAD were significant predictors of EPE when
      comparing their respective medians in individuals with tPSA greater than 4.0
      ng/mL. Statistically significant differences were noted between patients with and
      without EPE for tPSAD (P = 0.0015), cPSAD (P = 0.0018), and fPSAD (P = 0.0022),
      but not for the fPSA/tPSA, cPSA/tPSA, and fPSA/cPSA ratios. The area under the
      receiver operating characteristic curve was similar for tPSA (0.539) and cPSA
      (0.542), as it was for tPSAD (0.708), cPSAD (0.700), and fPSAD (0.731). The
      specificity and diagnostic accuracy of tPSAD, cPSAD, and fPSAD were significantly
      greater than those of tPSA and cPSA (specificity P <0.001; diagnostic accuracy P
      <0.05). CONCLUSIONS: In men with nonpalpable prostate cancer, the density
      parameters of tPSA, cPSA, and fPSA performed equivalently and appeared to enhance
      the predictability of EPE.

PMID- 14665356
TI  - Comparing PSA outcome after radical prostatectomy or magnetic resonance imaging
      guided partial prostatic irradiation in select patients with clinically localized
      adenocarcinoma of the prostate.
AB  - OBJECTIVES: To determine whether high-dose radiation delivered to a subvolume of
      the prostate gland (peripheral zone) using intraoperative magnetic resonance
      imaging-guided brachytherapy provided comparable 5-year prostate-specific antigen
      (PSA) control rates to radical prostatectomy (RP) in select patients compared
      prospectively but in a nonrandomized setting. METHODS: Between 1997 and 2002, 322
      and 196 patients with clinical Stage T1c, PSA less than 10 ng/mL, biopsy Gleason
      score 3 + 4 or less, and without perineural invasion underwent RP or
      intraoperative magnetic resonance imaging-guided brachytherapy, respectively, and
      had a 2-year minimal follow-up. Cox regression multivariable analysis was used to
      evaluate whether the initial therapy, pretreatment PSA level, biopsy Gleason
      score, percentage of positive biopsies, or prostate gland volume were predictors
      of the time to post-therapy PSA failure. PSA failure was estimated using the
      Kaplan-Meier method and defined using the American Society for Therapeutic
      Radiology Oncology consensus definition. RESULTS: Only the percentage of positive
      prostate biopsies (P(Cox) = 0.02) was a significant predictor of the time to post
      treatment PSA failure. However, the distribution of this parameter between RP and
      brachytherapy-treated patients was not significantly different (P(chi-square) =
      0.25). The initial therapy did not predict for the time to post-therapy PSA
      failure (P(Cox) = 0.18). The 5-year estimate of PSA control was 93% versus 95%
      (P(log-rank) = 0.16) for the RP and brachytherapy patients, respectively.
      CONCLUSIONS: Despite only partial prostatic irradiation using intraoperative
      magnetic resonance imaging-guided brachytherapy, similar 5-year estimates of PSA
      control were found for both brachytherapy and RP-managed patients.

PMID- 14665357
TI  - Salvage brachytherapy for local recurrence after radical prostatectomy and
      subsequent external beam radiotherapy.
AB  - OBJECTIVES: To evaluate the technical feasibility, safety, and efficacy of seed
      implantation for local recurrence after radical prostatectomy and external beam
      radiotherapy. METHODS: Between October 1999 and March 2002, 10 patients with
      targeted, histologically proven local relapse after surgery and subsequent
      external beam radiotherapy (only in 8 patients), underwent permanent
      brachytherapy with palladium-103 and iodine-125 after complete restaging. In all
      patients, an intraoperative morphovolumetric ultrasound study of the target was
      performed, with a planning target volume ranging from 5 to 26.7 cm(3). The
      preimplant prostate-specific antigen values ranged from 1.1 to 6.31 ng/mL.
      RESULTS: Postplan dosimetry was performed to determine the percentage of the
      target volume that received a dose equal to, or greater than, the prescribed dose
      (range 84.5% to 95.9%) and the dose that was delivered to the 90% of the target
      volume (range 85.08% to 129.43%). The urinary scores, measured using the
      International Prostate Symptom Score, had normalized at 3 months. Only 1 patient
      had worsened incontinence during the first 2 months, with subsequent restoration
      of the previous situation. The other patients did not have any changes in their
      previous clinical condition. One patient experienced occasional gross hematuria
      that had been present after external beam radiotherapy. No rectal complications
      were reported. After a median follow-up of 20.6 months, 7 patients showed a
      decreasing or stable prostate-specific antigen level. CONCLUSIONS: This
      preliminary experience has demonstrated that seed implantation of a neoplastic
      local recurrence is technically feasible and safe and allows for accurate
      dosimetry when the area to be treated can be defined by ultrasonography. Longer
      follow-up, accurate patient selection, and larger series of patients could help
      to better define the oncologic outcome.

PMID- 14665358
TI  - Importance of implant dosimetry for patients undergoing prostate brachytherapy.
AB  - OBJECTIVES: To evaluate the disease and treatment-related factors for predicting
      biochemical freedom from recurrence (BFR) in patients with clinically localized
      prostate cancer undergoing permanent prostate brachytherapy. METHODS: Between
      November 1992 and June 1998, 883 consecutive patients with T1-T2 prostate cancer
      underwent permanent prostate brachytherapy. Computed tomography-based dosimetry
      was performed, and the minimal dose to 90% of the prostate volume relative to the
      prescribed dose (D(90)) was calculated. BFR was defined as three prostate
      specific antigen (PSA) rises from nadir, with patients having one or two PSA
      rises censored early. Follow-up was calculated by censored events. Kaplan-Meier
      actuarial outcome was determined, and multivariate Cox regression analysis was
      performed to assess the significance of the D(90), initial PSA value, Gleason
      score, addition of external beam radiotherapy, addition of hormonal therapy, and
      isotope selection. RESULTS: The mean follow-up was 55 months (range 3 to 125).
      The 10-year BFR rate was 79.1%. Cox proportional analysis identified D(90) as a
      predictor of BFR (P <0.0001), along with Gleason score, initial PSA level, and
      clinical stage (P = 0.001, P = 0.001, and P = 0.011, respectively). The addition
      of external beam radiotherapy, hormonal therapy, and isotope selection did not
      have an impact on BFR (P = 0.128, P = 0.399, and P = 0.224, respectively).
      CONCLUSIONS: The quality of permanent prostate brachytherapy as measured by the
      D(90) was the most significant predictor for BFR in this study cohort at 10
      years. Furthermore, adding external beam radiotherapy and/or hormonal therapy as
      adjuvant therapies did not independently predict for BFR. Overall, the reported
      10-year BFR rates in this study were favorable. Strategies for ensuring the best
      quality implant should be used and, when reporting brachytherapy outcomes, the
      implant quality should be noted.

PMID- 14665359
TI  - Tissue factor expression and prognosis in patients with metastatic prostate
      cancer.
AB  - OBJECTIVES: To assess immunohistochemically the pattern of tissue factor (TF)
      expression in patients with metastatic prostate cancer, because TF is aberrantly
      expressed in human cancer. TF is the primary initiator of the coagulation
      cascade. METHODS: Seventy-three patients with untreated metastatic prostate
      cancer who received hormonal therapy were included in the present study. Biopsy
      specimens were stained with anti-human TF antibody. We evaluated the histologic
      grade, extent of bony metastasis, clinical response to hormonal therapy, and
      patient prognosis. RESULTS: TF was detected in 75.3% of the tumors of the
      patients with metastatic prostate cancer. TF expression showed no association
      with histologic grade, extent of bony metastasis, or clinical response to
      hormonal therapy. Patients with TF-positive tumors had a poorer cause-specific
      survival than those with TF-negative tumors. Multivariate analysis showed that TF
      expression, clinical response to hormonal therapy, and extent of bony metastasis
      were significant prognostic factors. CONCLUSIONS: The TF content measured using
      immunohistochemical staining was a useful prognostic factor for patients with
      metastatic prostate cancer treated with androgen withdrawal therapy.

PMID- 14665360
TI  - Contemporary management of superficial bladder cancer in the United States: a
      pattern of care analysis.
AB  - OBJECTIVES: To assess the practice preferences among urologists treating
      superficial bladder cancer in the United States. METHODS: We surveyed 226
      urologists using a specially designed survey instrument. The type of practice,
      number of urologists in group practice, annual volume of patients with bladder
      cancer, and those treated with intravesical therapy were assessed. We also
      obtained information on the American Urological Association section and year of
      graduation from urology residency training. RESULTS: Of the 226 contacted
      urologists, 105 (46%) returned a completed survey instrument. Seventeen percent
      were practicing in academic institutions and 63% were in independent community
      practice. Forty-five percent had graduated from urology training in or before
      1985. Thirty-six percent were in small and 37% were in moderate-size groups.
      Thirty-five percent were treating a moderate number of patients with bladder
      cancer, and 44% were treating a large number of patients annually. Thirty-two
      percent had a moderate number and 40% had a large number of patients receiving
      intravesical therapy annually. Immunotherapy was preferred in patients at high
      risk of recurrence. Intravesical chemotherapy was preferred by many for
      immunotherapy failure. The type of practice and year of graduation were the
      factors most frequently affecting treatment choice. CONCLUSIONS: Practice
      preferences for the management of superficial bladder cancer are in general
      agreement with the American Urological Association Bladder Cancer Guidelines
      Panel recommendations. However, 81% of surveyed urologists were still reluctant
      to refer patients with high-grade Ta-T1 disease with failure after intravesical
      immunotherapy twice for more aggressive therapy such as cystectomy or
      radiotherapy.

PMID- 14665361
TI  - En bloc transurethral resection of bladder tumors: use and limits.
AB  - OBJECTIVES: To evaluate the feasibility and safety of transurethral en bloc
      resection of bladder tumors using a flat loop. Transurethral en bloc resection of
      bladder tumors facilitates pathologic evaluation. METHODS: A total of 37 patients
      with papillary transitional cell carcinoma of the bladder underwent transurethral
      en bloc resection with the use of a flat loop electrode. RESULTS: In 37 patients,
      62 lesions were removed using a flat loop to perform the en bloc technique. This
      method is safe to perform in the case of papillary tumors with a diameter of up
      to 25 mm and that are found in specific areas of the bladder. CONCLUSIONS: It is
      both safe and feasible to perform en bloc resection with a flat loop electrode
      but attention must be paid to the limitations of this technique. Excellent
      pathologic evaluation of the grade and stage of the removed specimen is possible.

PMID- 14665362
TI  - Clinical outcome after retroperitoneal lymphadenectomy of patients with pure
      testicular teratoma.
AB  - OBJECTIVES: To determine the pathologic findings and clinical outcome of patients
      with pure teratoma of the testis who underwent primary or postchemotherapy
      retroperitoneal lymphadenectomy (RPLND). METHODS: From January 1989 to February
      1998, 29 patients with pure testicular teratoma underwent primary (n = 11) or
      postchemotherapy (n = 18) RPLND. RESULTS: Overall, 23 (79%) of 29 patients had
      retroperitoneal disease, with 18 (62%) initially presenting with advanced
      disease. The pathologic stage in the 11 patients undergoing primary RPLND was pN0
      in 6 (55%), pN1 in 3 (27%), and pN2 in 2 (18%). Of the 7 patients with clinical
      Stage I undergoing primary RPLND, 1 had teratoma and 1 had seminoma in the
      retroperitoneum; of the 4 patients with clinical Stage IIA, 2 had teratoma and 1
      had embryonal carcinoma. Four patients were lost to follow-up and the other seven
      had no evidence of disease (NED) at a median follow-up of 90.4 months, with no
      relapses. The pathologic findings in the 18 patients undergoing postchemotherapy
      RPLND revealed fibrosis in 8, teratoma in 9, and yolk sac tumor in 1. At last
      follow-up, 7 of the 9 patients with teratoma were NED, 1 was dead of disease, and
      1 was dead of unknown causes. Of the 8 patients with fibrosis, 6 had NED and 2
      were lost to follow-up. The patient with viable cancer had NED at last follow-up.
      CONCLUSIONS: These data underscore the metastatic potential of pure testicular
      teratoma. A significant proportion (45%) of patients with low-stage pure
      testicular teratoma had retroperitoneal disease. Furthermore, a high proportion
      (62%) presented initially with advanced disease and demonstrated a considerable
      risk of relapse despite complete resection or favorable histologic features in
      the resected retroperitoneal specimen.

PMID- 14665363
TI  - Effect of chronic diseases on incidence of erectile dysfunction.
AB  - OBJECTIVES: To estimate the incidence of erectile dysfunction (ED) in a
      population-based sample during 5 years' follow-up and determine how the rate was
      affected by age and medical conditions. METHODS: The target population comprised
      all men aged 50, 60, or 70 years residing in the study area at the time the study
      began. Questionnaires were mailed to 3143 men in 1994 and to 2864 men in 1999.
      The follow-up sample consisted of the 1442 men who responded to both the baseline
      and the follow-up questionnaires. ED was assessed by two questions concerning the
      subject's ability to achieve and maintain an erection sufficient for intercourse.
      We estimated the incidence of minimal ED among the 391 men free of ED, of
      moderate ED in the 1130 with no or minimal ED, and of complete ED among the 1323
      men free of complete ED at baseline. RESULTS: The incidence of minimal ED was 127
      cases per 1000 person-years (95% confidence interval 110 to 148). For moderate
      ED, it was 41 (95% confidence interval 36 to 47) and for complete ED, it was 18
      (95% confidence interval 15 to 22). The incidence of minimal ED increased 40% and
      moderate ED 80% with each decade increment in age; the incidence of complete ED
      increased 190%. The incidence of ED was increased in men with diabetes (rate
      ratio 2.4 for minimal, 2.6 for moderate, and 3.4 for complete ED). Hypertension,
      heart disease, arthritis, pulmonary disease, and cerebrovascular disease had
      little or no effect on the incidence of ED. CONCLUSIONS: ED is a commonly
      occurring disorder that increases in incidence strongly between 50 and 75 years
      of age. Diabetes is a major determinant of ED, but hypertension, heart disease,
      arthritis, and cerebrovascular disease increase the incidence of ED only
      marginally.

PMID- 14665364
TI  - Long-term potency after iodine-125 radiotherapy for prostate cancer and role of
      sildenafil citrate.
AB  - OBJECTIVES: To assess the long-term sexual potency and attrition in sexual
      function after iodine-125 ((125)I) seed radiotherapy and the effect of sildenafil
      on radiation-induced erectile dysfunction (ED). METHODS: This prospective study
      consisted of 86 sexually active patients (mean age 63.5 +/- 7.7 years) who
      underwent (125)I seed implantation from 1997 to 1999 to treat low-volume prostate
      cancer (prostate-specific antigen less than 10 ng/mL, Gleason score 6 or less,
      stage T1-T2). All patients were followed up every 6 to 8 months for 4 years.
      Patients prescribed sildenafil citrate for ED completed the abridged five-item
      version of the International Index of Erectile Function (IIEF) and the Erectile
      Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires. RESULTS:
      The median follow-up was 49.7 months (range 36 to 66). Of 86 patients, 43 (50%)
      did not initiate drug therapy; and only 36 (83.7%) of the 43 were interviewed at
      4 years. Twenty-three (63.8%) of the 36 patients had erections sufficient for
      vaginal penetration, with a total mean +/- SD IIEF-5 score of 15.76 +/- 1.13. The
      other 50% (43 of 86) initiated sildenafil citrate for treatment of ED after seed
      implantation, with a minimal follow-up of 6 months. At 4 years, 32 (74%) of the
      43 were responding positively to sildenafil citrate, with a total IIEF-5 score of
      18.3 +/- 1.2. The mean EDITS +/- SD score was 76.5 +/- 3.2, and the spousal
      satisfaction rate was 72% (31 of 43). The dropout rate was 37% (16 of 43); 10
      (63%) of the 16 discontinued because of a lack of efficacy, 3 (19%) because of a
      return of natural erections sufficient for vaginal penetration, and 3 (19%)
      discontinued because of side effects (headaches). CONCLUSIONS: ED is a major long
      term issue after (125)I seed radiotherapy, with a long-term potency rate of 29%.
      Sildenafil citrate improves erections in most patients after (125)I seed
      implantation.

PMID- 14665365
TI  - Pelvic and extremity immobilization after bladder exstrophy closure:
      complications and impact on success.
AB  - OBJECTIVES: A successful initial bladder closure is critical to the development
      of adequate bladder capacity and ultimate continence among patients with bladder
      exstrophy. Although secure pelvic fixation is essential to success, the various
      methods of pelvic and extremity immobilization and their impact on surgical
      outcome have not previously been examined. METHODS: A review of the approved
      bladder exstrophy database at our institution identified 194 patients for whom
      data were available regarding initial bladder closure and the method of pelvic
      immobilization. The records were reviewed with respect to age at bladder closure,
      use/type of osteotomy, method of pelvic immobilization, complications related to
      the immobilization technique, and surgical outcome. RESULTS: Of 194 patients
      identified, initial exstrophy closure failed in 86. Of these 86 patients, the
      initial closure failed in 80 at another hospital who were referred to our
      institution for additional treatment. Of the 114 initially closed at this
      institution, 6 failed. The success rates for initial and second closures were
      highest after osteotomy (75% versus 38% and 81.5% versus 27%, respectively), and
      when the patients were immobilized with an external fixator and 6 to 8 weeks of
      modified Buck's traction with osteotomy (96%) or 4 to 6 weeks of modified
      Bryant's traction without osteotomy (61%). The spica cast and "mummy wrapping"
      immobilization techniques were less effective and were associated with
      significant complications. CONCLUSIONS: These results demonstrate that a
      successful exstrophy bladder closure depends on the proper use of the osteotomy
      and effective postoperative immobilization of the pelvis. Our best outcomes have
      been achieved using lower extremity traction (with or without external fixation
      of the pelvis).

PMID- 14665366
TI  - Anterior extraperitoneal approach to laparoscopic pyeloplasty in horseshoe
      kidney: a novel technique.
AB  - We describe a novel technique of laparoscopic pyeloplasty in the horseshoe kidney
      with ureteropelvic junction obstruction using an anterior extraperitoneal
      approach. The surgical technique is associated with satisfactory clinical
      outcomes. Additional studies are necessary to evaluate its potential as an
      alternative to the existing approaches to laparoscopic pyeloplasty.

PMID- 14665367
TI  - Upper quadrant access for urologic laparoscopy.
AB  - Initial access into the peritoneum and establishing pneumoperitoneum are required
      for laparoscopy. Various techniques have been described to achieve insufflation
      and place trocars. We describe our method of initial entry into the upper
      quadrant and subsequent incorporation of this site as a working port during upper
      urinary tract laparoscopy. This is an easy and safe means of entering the
      peritoneum, even after prior surgery, and provides a functional trocar for
      retraction and dissection.

PMID- 14665368
TI  - Persistent Mullerian duct syndrome with transverse testicular ectopia.

PMID- 14665369
TI  - Migration of a dislodged tip of an ultrasound lithotripter probe to the pulmonary
      artery: a rare complication of percutaneous nephrolithotomy.
AB  - A 44-year-old man underwent percutaneous nephrolithotomy for a left renal
      staghorn stone. During the procedure, the tip of the ultrasound lithotripter
      dislodged from the probe rod when the renal stone was being disintegrated. The
      tip immediately disappeared from the field of nephroscopic vision. Despite a
      thorough search, the tip could not be found. Postoperative chest radiography
      revealed a foreign body, shaped like a lithotripter probe tip, located in the
      lingular branch of the left pulmonary artery. Eventually, left thoracotomy was
      performed to remove the foreign body. To our knowledge, this rare complication
      has never been reported before.

PMID- 14665370
TI  - An American hijra: a report of a case of genital self-mutilation to become
      India's "third sex".
AB  - We report a case of male genital self-mutilation related to the subject's desire
      to become a "hijra," the "third sex" described in East Indian mythology. The
      patient is the first American hijra of which we are aware. He emasculated
      himself, performed a penectomy, and created a perineal urethrostomy. This report
      adds another potential cause for genital mutilation of which the urologist should
      be aware, along with accidents, gender dysphoria, psychotic self-injurious
      behavior, and assault.

PMID- 14665371
TI  - Laparoscopic removal of Mullerian structures and orchiopexy for persistent
      Mullerian duct syndrome.
AB  - A 1-year-old boy presented for evaluation of bilateral undescended testes.
      Diagnostic laparoscopy was conducted, and uterine tissue with bilateral gonads
      was detected in the rectovesical fossa. Chromosomal analysis revealed a 46,XY
      karyotype. Persistent mullerian duct syndrome was diagnosed, and laparoscopic
      surgery was performed to treat this condition. The uterus was incised at a distal
      site and withdrawn through the port. The bilateral testes were fixed in the
      scrotum. The patient was discharged 3 days later. We believe that the
      laparoscopic approach is a valid, alternative choice to traditional surgery for
      resolution of this condition, permitting minimally invasive surgery.

PMID- 14665372
TI  - Stromal testis tumors in infants. a report of two cases.
AB  - Gonadal stroma tumors account for 8% of pediatric testicular tumors and are
      therefore exceedingly rare. They generally exhibit a benign behavior. We report
      two consecutive cases of gonadal stroma tumors in infants. A 5-month-old boy
      presented with a Sertoli cell tumor and a 2-month-old boy with a juvenile
      granulosa cell tumor without systemic disease. Both were diagnosed incidentally
      during routine examinations. Organ-sparing surgery and radical orchiectomy,
      respectively, was the therapy of choice. Although neonatal testicular tumors are
      rare, they should be considered in the differential diagnosis of a newborn with a
      scrotal mass.

PMID- 14665373
TI  - Simultaneous laparoscopic prosthetic mesh inguinal herniorrhaphy during
      transperitoneal laparoscopic radical prostatectomy.
AB  - Concurrent repair of inguinal hernias during open radical retropubic
      prostatectomy is well described and commonly practiced. With the advent of the
      laparoscopic approach to radical prostatectomy, the possibility of concurrent
      laparoscopic hernia repair merits investigation. We present a case of
      simultaneous prosthetic mesh onlay hernia repair for bilateral inguinal hernias
      during laparoscopic transperitoneal radical prostatectomy.

PMID- 14665374
TI  - Laparoscopic robotic-assisted ileal conduit urinary diversion in a quadriplegic
      woman.
AB  - Urinary diversion is a therapeutic option in quadriplegic patients with poor
      lower urinary tract conditions, but it is an invasive procedure. Laparoscopic
      techniques are less invasive, but are technically demanding, and only a few
      surgical teams are able to complete such a complex procedure endoscopically.
      Robotics bring an unprecedented control of surgical instruments, shorten the
      learning curve, and allow open surgeons to apply more easily their technical
      skill to the laparoscopic approach. This complex case of laparoscopic ileal
      conduit in a quadriplegic woman was completed by our team with the Da Vinci
      system after 6 months of clinical experience in robotic surgery.

PMID- 14665375
TI  - Lipid peroxidation and its correlations with urinary levels of oxalate, citric
      acid, and osteopontin in patients with renal calcium oxalate stones.
AB  - OBJECTIVES: To determine whether lipid peroxidation plays a role in patients with
      calcium oxalate kidney stones and to determine the correlation of lipid
      peroxidation with tubular damage and the major urinary risk factors. We also used
      the isoenzymes of glutathione S-transferase (GST) to examine which parts of the
      renal tubules were injured in patients with renal stones. METHODS: This clinical
      study included two study groups. Group 1 included 32 normal volunteers, and group
      2 included 32 patients with calcium oxalate kidney stones. A 24-hour urine sample
      was collected from each subject, and the levels of Ca, P, Mg, oxalate, citrate, N
      acetyl-beta-glucosaminidase (NAG), beta-galactosidase (GAL), alphaGST, piGST,
      osteopontin (OPN), thiobarbituric acid-reactive substances (TBARS), and
      malondialdehyde (MDA) were examined. RESULTS: Hyperoxaluria, hypocitraturia, and
      low urinary OPN were the major abnormalities found in the patients with stones.
      Elevated urinary alphaGST, NAG, and GAL were also noted in the patients with
      stones; however, urinary piGST showed no statistically significant difference
      compared with the controls. Urinary TBARS and MDA had statistically significant
      correlations with alphaGST, GAL, NAG, Ca, and oxalate, but had no correlation
      with piGST, citrate, OPN, Mg, and P. Urinary citrate had a negative, linear, and
      statistically significant correlation with alphaGST, GAL, and NAG. CONCLUSIONS:
      Lipid peroxidation correlated with hyperoxaluria and renal tubular damage,
      indicating that hyperoxaluria can induce tubular cell injury and that this injury
      may be due to the production of free radicals in patients with calcium oxalate
      stones. Renal tubular damage in patients with stones may be limited to the
      proximal tubules.

PMID- 14665376
TI  - Structural and vascular response of normal and obstructed rabbit whole bladders
      to distension.
AB  - OBJECTIVES: To investigate the structural and morphologic effect of distension
      after partial outlet obstruction in rabbits. METHODS: Thirty male New Zealand
      white rabbits were separated into two groups: control (sham) and partial outlet
      obstruction (3 weeks). Three rabbits from each group were distended to 5%, 25%,
      50%, 100%, and 125% of capacity. Each bladder was fixed at the volume in buffered
      formalin for 6 to 8 hours. Sections of dorsal and ventral bladder were blocked,
      and cross sections were evaluated. Quantitative morphometry was performed, and
      CD31 immunohistochemistry was used to characterize the vascularity. RESULTS:
      Partial outlet obstruction resulted in increased bladder weight and capacity and
      increased thickness of the mucosa, submucosa, detrusor, and serosa. In the
      control bladder, the greatest thinning was seen between 5% and 25% capacity, and
      in the obstructed group, the greatest thinning occurred between 25% and 50%. The
      level of vascular collapse was significantly greater for the control bladders
      than for the obstructed bladders at all levels of distension. Finally, the
      obstructed bladders showed a significantly greater level of vascularity in the
      submucosa than the control bladders. CONCLUSIONS: Normal bladder distension
      resulted in significant morphologic changes when the bladder was distended to 25%
      of capacity but changed relatively little between 25% and 125%. However,
      distension of the obstructed bladder resulted in significant morphologic changes
      when the bladder was distended from 25% to 50% of capacity but changed relatively
      little between 50% and 125%.

PMID- 14665377
TI  - Analysis of genetic alterations in normal bladder urothelium.
AB  - OBJECTIVES: To determine whether normal mucosa had already acquired genetic
      changes, we analyzed the loss of heterozygosity (LOH) and chromosomal changes in
      normal urothelium from patients with bladder cancer and those without any history
      of bladder cancer. METHODS: Sixteen patients with bladder cancer and 15 patients
      with benign prostatic hyperplasia were included in this study. Tumor tissue, as
      well as macroscopically normal mucosa, was examined histopathologically. We
      performed comparative genomic hybridization according to standard protocols to
      detect chromosomal alterations. Furthermore, we analyzed LOH using four markers
      on chromosome 9 according to standard protocols for polymerase chain reaction.
      RESULTS: In 75% of tumor samples, LOH or shifts were detected at least with one
      marker on chromosome 9. Comparative genomic hybridization revealed chromosomal
      alterations in 12 (75%) of 16 tumors. The loss of chromosome 9 was seen
      frequently (56%). LOH was observed in normal mucosa in 5 of 16 patients with
      tumor and 1 of 15 patients with benign prostatic hyperplasia. Chromosomal
      alterations were also seen in the normal mucosa of 1 patient with tumor and 2
      patients with benign prostatic hyperplasia (chromosomes 1, 2, 6, 14, and 17).
      CONCLUSIONS: Our results indicated that no general genetic instability is present
      in the bladder urothelium. Therefore, in most patients with bladder cancer, it
      seems that multifocality and recurrence are not caused by genetic instability of
      normal urothelial cells but develop owing to cell migration or intraluminal
      spread.

PMID- 14665378
TI  - Laparoscopic heminephrectomy using a new fibrin sealant powder.
AB  - OBJECTIVES: To determine the ability of a hemostatic fibrin sealant powder
      (HFSP), delivered laparoscopically, to achieve hemostasis and seal the collecting
      system during laparoscopic heminephrectomy. METHODS: An HFSP preparation was
      applied laparoscopically as a dry powder spray. Twenty-two farm pigs were
      randomized into two laparoscopic heminephrectomy groups: group 1 underwent
      conventional intracorporal suturing with vascular control (n = 11) and group 2
      received HFSP application alone with regional ischemia (n = 11). Computed
      tomography was performed at 48 hours and again 6 weeks postoperatively. RESULTS:
      The operative findings revealed no differences between the two groups in the
      weight of the removed segments, mean arterial blood pressure, operating room
      time, estimated blood loss, or hematocrit and serum creatinine levels. The gross
      examination 6 weeks postoperatively found no delayed bleeding, urinoma formation,
      or bowel adhesions. The computed tomography findings at 48 hours postoperatively
      demonstrated excellent hemostasis in both groups. Urinary extravasation was
      detected in 8 (80%) of 10 animals in the HFSP group and 1 (9%) of 11 in the
      conventional group at 48 hours (P < 0.008). At the 6-week computed tomography
      evaluation, none of the animals showed evidence of urinoma or hematoma formation.
      Histopathologically, at 6 weeks, the cut surface of the kidneys in both groups
      had been replaced by dense scar tissue at the cortex with a sharp line of
      demarcation between the scar and normal kidney. CONCLUSIONS: HFSP greatly
      facilitates laparoscopic heminephrectomy by providing rapid and lasting
      hemostasis without suturing. Early urine extravasation was more common in the
      HFSP group, but no clinical, gross, or radiographic evidence of urinoma formation
      was seen in either group 6 weeks after surgery.

PMID- 14665379
TI  - Bipolar needle electrocautery for laparoscopic partial nephrectomy without renal
      vascular occlusion in a porcine model.
AB  - OBJECTIVES: To report a novel method of accomplishing laparoscopic lower pole
      partial nephrectomy in an acute porcine model using a bipolar needle electrode
      without the need for renal arterial occlusion. METHODS: Six animals (12 renal
      units) underwent laparoscopic polar nephrectomy using the bipolar needle
      electrode. After complete laparoscopic mobilization of the lower pole of the
      kidney, the bipolar needle electrode was repeatedly inserted full-thickness into
      the renal parenchyma and applied transversely, creating regional ischemia to the
      entire lower pole without renal vascular occlusion. The specimen was then
      amputated using laparoscopic scissors. RESULTS: For the 12 laparoscopic partial
      nephrectomies, the mean operative time was 39 +/- 30 minutes, and the mean blood
      loss was 90 +/- 112 mL. Of the 12 cases, 10 (83%) were performed successfully
      with the bipolar needle electrocautery as the only source of hemostasis and
      without the need for ancillary hemostatic measures. Two of the procedures (17%)
      required temporary arterial control for hemostasis. For the successful
      procedures, the mean operative time was 29 +/- 4 minutes, and the mean blood loss
      was 48 +/- 11 mL. Histologic analysis of the specimens demonstrated coagulative
      necrosis between 2 and 4 mm from the line of the surgical incision. CONCLUSIONS:
      Bipolar needle electrocautery is a promising device that can be used to
      facilitate laparoscopic partial nephrectomy with minimal blood loss and without
      the need for renal arterial occlusion and warm ischemia. Additional studies are
      required to optimize the delivery parameters of this device.

PMID- 14665380
TI  - Terry Allen's career in pediatric urology.

PMID- 14665382
TI  - Onset of hepatic erythropoiesis after malarial infection in mice.
AB  - Plasmodium yoelii-infected erythrocytes were injected into mice with or without
      6.5 Gy irradiation. This irradiation suppressed erythropoiesis and induced severe
      immunosuppression. However, these mice showed a rather delayed infection,
      suggesting that fresh erythrocytes may become malarial targets. In other words,
      malarial infection did not persist without newly generated erythrocytes in mice.
      We then examined erythropoiesis in the liver and bone marrow of mice with
      malaria. Surprisingly, erythropoiesis began in the liver. At this time, the serum
      level of erythropoietin (EPO) was prominently elevated and the EPO mRNA also
      became detectable in the kidney. Many clusters of red blood cells appeared de
      novo in the parenchymal space of the liver. These results revealed that malarial
      infection had a potential to induce the onset of hepatic erythropoiesis in mice.

PMID- 14665383
TI  - Serological differentiation of acute and chronic schistosomiasis using
      Schistosoma mansoni recombinant protein RP26.
AB  - We obtained a recombinant protein encoded by Schistosoma mansoni gene which was
      able to differentiate acute from chronic schistosomiasis when applied as antigen
      in enzyme-linked immunosorbent assay (ELISA). A cDNA clone encoding a 26 kDa
      recombinant protein (RP26) was selected by screening of an adult worm S. mansoni
      lambdaZAP expression library with rabbit sera produced against PIII, an adult
      worm protein fraction already known to possess protective and immunomodulating
      effects. The clone cDNA presented 99% identity with S. mansoni Sm22.3 gene. We
      assayed IgG reactivity of sera from 18 patients with acute, 25 patients with
      chronic S. mansoni infection and 20 uninfected donors with RP26 in ELISA. Our
      results showed that 89% of sera were positive in acute schistosomiasis group, and
      only 26% in chronic group, without false-positive reactions in uninfected group.
      In mice the immune response to RP26 increased up to week 9 after infection and
      then diminished. We proposed that production of antibodies binding to RP26
      stopped at the chronic stage of disease. The testing of sera from eight other
      parasitic infections with RP26 revealed no positive reactions in majority of
      sera. However, we observed low positive reaction in sera from 20% of
      leishmaniasis patients. Our results indicate that a recombinant protein RP26 can
      be used as immunodiagnostic reagent for detection of acute phase of
      schistosomiasis mansoni.

PMID- 14665384
TI  - Production and characterisation of monoclonal antibodies to ovine interleukin-5.
AB  - Monoclonal antibodies (MAbs) were developed against recombinant ovine interleukin
      5 (IL-5) produced in the baculovirus expression vector system. One MAb, D11
      (isotype IgG1), neutralised the activity of both recombinant and native sources
      of IL-5 in a biological assay (Baf cell assay) but was only weakly reactive in
      immunocytochemistry. Conversely, a second MAb, A8 (isotype IgA), successfully
      detected IL-5 in immunocytochemistry but did not display neutralising activity.
      The development of these MAbs will enable the assay of ovine IL-5 in vitro and
      permit studies into the role of hypersensitivity reactions in sheep by
      neutralisation of IL-5 in vivo.

PMID- 14665385
TI  - Transcription of metabolic enzyme genes during the excystation of Giardia
      lamblia.
AB  - The present study evaluates the expression of genes of Giardia lamblia, one of
      the most simple and most early diverging eukaryotes, that encode the metabolic
      enzymes pyruvate: ferredoxin oxidoreductase (PFOR), acetyl-CoA synthetase (ACS),
      alcohol dehydrogenase E (ADHE) and glutamate dehydrogenase (GDH) and the cyst
      wall protein (CWP1) gene in trophozoites, cysts and during the excystation
      process. Primers were designed to amplify mRNA fragments through quantitative
      reverse-transcriptase-polymerase-chain-reaction. In trophozoites, all transcripts
      of the enzymes studied were present. In cysts, three of the transcripts were
      detected: CWP1, GDH and ACS; but the relative levels of the mRNA of GDH and ACS
      were very different between trophozoites and cysts. During excystation, PFOR and
      ADHE transcripts appeared after the first induction phase, and the mRNAs of ACS
      and GDH increased throughout the process.

PMID- 14665386
TI  - Further morphological studies on the behavior of Trypanosoma rangeli in the
      hemocytes of Rhodnius prolixus.
AB  - The hemocytes of Rhodnius prolixus were analyzed during the course of infection
      with the protozoan Trypanosoma rangeli. The following cell types were identified:
      prohemocyte, plasmatocyte, adipocyte, granular cell and oenocytoid. The number of
      these cells changes during the infection course thus indicating a cell response
      to infection of R. prolixus by T. rangeli. Transmission electron microscopy
      showed that plasmatocytes were able to ingest epimastigote forms of the parasite,
      which were then found within a parasitophorous vacuole. Amorphous material was
      seen within the vacuole suggesting that fusion of host cell lysosomes with the
      vacuole took place. Intravacuolar parasites in process of digestion were
      observed. In addition, reaction product indicative of the presence of acid
      phosphatase was observed in parasite-containing vacuoles. No dividing parasites
      were seen within the vacuole in contrast to what was observed outside the host
      cells.

PMID- 14665388
TI  - History of Katayama disease: schistosomiasis japonica in Katayama district,
      Hiroshima, Japan.
AB  - Historical account of Katayama disease is presented as a centenary record since
      the discovery of Schistosoma japonicum in Japan in 1904. The ever unknown endemic
      disease was called Katayama disease. Katayama district, Hiroshima Prefecture is
      one of endemic areas of schistosomiasis japonica in Japan. The causative parasite
      was first discovered in a human case in Katayama district. After the discovery of
      the parasite, life history, diagnosis, treatment, control measures and even
      eradication have been worked out, attempted and succeeded in Katayama district
      together with other endemic areas in Japan. Hiroshima Prefecture declared safety
      from the disease in 1980.

PMID- 14665389
TI  - Historical view of schistosomiasis japonica in Japan: implementation and
      evaluation of disease-control strategies in Yamanashi Prefecture.
AB  - We summarized historical aspects of disease control activities targeting
      schistosomiasis japonica in Kofu basin, Yamanashi Prefecture, Japan. Kofu Basin
      was one of the biggest endemic foci of schistosomiasis japonica in Japan, and the
      last place where transmission of Schistosoma japonicum was confirmed in Japan.
      Because of the most severe endemic situations in Yamanashi, intensive control
      measures had been implemented by the central as well as the local government. The
      last human case in Japan was in 1977, which is just before praziquantel being
      available. Therefore, the main efforts were focused on snail control. Mass
      examination and mass chemotherapy were implemented, however, the compliance was
      not so good because of the severe side effects due to the available therapeutics,
      Stibnal. Along with socioeconomic development after World War II, big changes in
      land use, life style, and farming led drastic reduction in the disease prevalence
      in Kofu Basin in the 1960s. A large amount of budget was also used for disease
      control. Cementing water canals covered more than 95% of paddy fields in Kofu
      Basin, and this resulted in ecological changes. After elimination of
      schistosomiasis, environmental repair is the urgent subject in Kofu Basin. Our
      experiences in Yamanashi contain both good influences and also a lot of
      reflection. It is important to evaluate each activity in our history before we
      give intensive cooperation with countries where endemic foci is still present.

PMID- 14665390
TI  - A historical view of schistosomiasis japonica in the Chikugo river basin. What
      can we learn from autopsy?
AB  - Three hundred and forty-nine autopsy cases of schistosomiasis japonica were
      divided into two groups, based on the pathomorphology. Frequent regressive
      hepatic lesions such as active schistosomal lesion and destruction of limiting
      plates characterized the first group. The second group showed reparative hepatic
      lesions such as regeneration of the collapsed parenchyma, newly formed limiting
      plates and subsequent narrowing and disappearance of fibrous septa. Complications
      of liver cirrhosis and hepatocellular carcinoma related to viral hepatitis B
      and/or C also increased. Clonorchiasis was consistently found in both groups.

PMID- 14665391
TI  - Origin and evolution of Schistosoma japonicum.
AB  - In his hypothesis on the coevolution of Asian schistosomes and snails, Davis
      implies that the ancestors of the Schistosoma japonicum and S. indicum species
      group were African and arrived in Asia via the Indian plate. This paper briefly
      reviews molecular phylogenetic relationships among species of the genus
      Schistosoma to test Davis' theory about the origin and evolution of S. japonicum.
      All analyses using DNA base sequences, mitochondrial genome gene order and C
      banding patterns suggest that Schistosoma originated in Asia and not Africa.

PMID- 14665392
TI  - Cytokine regulation in experimentally-induced Schistosoma japonicum egg granuloma
      formation.
AB  - The formation of granulomas in host tissues in response to trapped Schistosoma
      japonicum eggs is central to the etiology of schistosomiasis. However, analysis
      of the host hypersensitivity reactions that result in granuloma formation, in
      schistosome infection, is not without difficulty. This is due, in part, to the
      fact that the parasites continuously deposit their eggs as clusters. In order to
      synchronize host reactions, we established an experimental model of hepatic
      granuloma formation whereby in vitro laid schistosome eggs are implanted directly
      into normal and cytokine-deficient mice livers. This model, validated by
      comparison with an infection model, was used to analyze cytokine regulation of
      granuloma formation around S. japonicum eggs. Combined models of implantation and
      cercarial infection were also studied. With special reference to IL-4, IL-13, IFN
      gamma and IL-18, our in vitro schistosome egg implantation model has shed new
      light on the roles of cytokines in both the acute and chronic stages of
      schistosome egg-induced granuloma formation.

PMID- 14665393
TI  - Haemostatic abnormalities in hepatosplenic schistosomiasis mansoni.
AB  - Hepatosplenic schistosomiasis is a complex immuno-regulatory disease and is major
      health problem in endemic countries. Acute bleeding is one of its most serious
      complications and often life-threatening. Clinical studies have demonstrated that
      the patients with hepatosplenic schistosomiasis are prone to develop complex
      haemostatic abnormalities that may be linked to the potential risk of bleeding
      from ruptured esophageal varices in these patients. The deficit in haemostatic
      parameters is more pronounced with the advancement of the disease and is maximal
      in the patients with experience of haematomesis. Evidences of enhanced generation
      of thrombin and plasmin indicate the presence of low-grade DIC in advanced
      hepatosplenic schistosomiasis, which is considered as a principal cause of
      haemostatic abnormalities in this endemic disease. Demonstration of procoagulant
      expression in peripheral blood monocytes of the patients and in the livers,
      spleens and intestines of S. mansoni-infected mice suggest their possible
      implication in the causation of DIC in S. mansoni infections. Moreover, because
      in vitro analysis indicates a participation of immune mechanisms in the localized
      procoagulant expression, it seems likely that the immune responses to
      schistosomes play a major role in the pathogenic mechanisms of haemostatic
      abnormalities in hepatosplenic schistosomiasis.

PMID- 14665394
TI  - Analysis of egg antigens inducing hepatic lesions in schistosome infection.
AB  - In schistosomiasis, granuloma formation to parasite eggs signals the beginning of
      a chronic and potentially life-threatening disease. Granulomas are strictly
      mediated by CD4+ T helper (Th) cells specific for egg antigens; however, the
      number and identity of these T cell-sensitizing molecules are largely unknown. We
      have used monoclonal T cell reagents as probes to track down, isolate and
      positively identify several egg antigens; this approach implicitly assures that
      the molecules of interest are T cell immunogens and, hence, potentially
      pathogenic. The best-studied egg component is the Sm-p40 antigen. Sm-p40 elicits
      a strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which
      are characterized by severe egg-induced immunopathology. Two additional described
      T cell-sensitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate
      carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx-1). In contrast to
      Sm-p40, both of these molecules induce a more balanced Th-1/Th-2 response, and
      are relatively stronger antigens in C57BL/6 mice, which develop smaller egg
      granulomas. Other components, including moieties with molecular weights of 25 kDa
      (Sm-p25), 150/166 kDa (Sm-p155/166), and 29 kDa (Sm-GST29), are also found to
      stimulate specific T cells. These findings in the murine model introduce the
      important notion that egg antigens can vary significantly in immunogenicity
      according to the host's genetic background. A better knowledge of the principal
      immunogenic egg components is necessary to ascertain whether such responses can
      be manipulated for the purpose of reducing pathology.

PMID- 14665395
TI  - Existence of host DNA sequences in schistosomes--horizontal and vertical
      transmission.
AB  - The localization of repetitive DNA sequences in the mouse genome such as mouse
      type 2 Alu sequence (B2) and mouse retrovirus-related sequences was shown in the
      body of adult Schistosoma japonicum and Schistosoma mansoni by applying an in
      situ PCR and hybridization technique. Using the same method, mouse major
      histocompatibility complex (MHC) class I sequence was also found in schistosomes.
      Furthermore, mouse MHC class I sequence and type A retroviral sequence were
      detected in S. japonicum and S. mansoni cercarial DNA by blot hybridization.
      These findings indicated that horizontal and vertical transmission of host DNA
      sequences occurred in schistosomes. The incorporation and propagation of host
      sequences in schistosomes and the roles played by such host sequences form the
      focus of this brief review.

PMID- 14665396
TI  - Clinical features of cerebral schistosomiasis, especially in cerebral and
      hepatosplenomegalic type.
AB  - Clinical features of cerebral schistosomiasis type (CST) and hepatosplenic
      schistosomiasis type (HST), and typical cases of each type were presented.
      Results of comparative study of clinical symptoms of both type among three
      countries in Japan, China and Philippines were discussed. CST in Japan and HST in
      the Philippines showed unique profiles when they were compared with those in
      other two countries. Although the reason for the difference is not clear, it
      might be determined by infection burden, pathogenicity of schistosome and/or
      immune response to the parasite antigen in human hosts.

PMID- 14665397
TI  - Imaging diagnosis of schistosomiasis japonica--the use in Japan and application
      for field study in the present endemic area.
AB  - For detecting lesions-related schistosomiasis japonica, X-rays, scintillation
      scanning, ultrasonography (US), computed tomography (CT), magnetic resonance (MR)
      and endoscopic examinations with biopsies have been used in Japan. Liver fibrosis
      and calcified changes are detected by US and CT. Most of the lesions that are
      detected by endoscopic examinations are due to deposited ova of Schistosoma
      japonicum. Portal hypertension is detected by US, CT and gastroscopic
      examination. Because schistosome infection decreased rapidly in Japan, most of
      the studies on imaging diagnosis were performed on chronic lesions or sequelae of
      schistosomiasis. Most of the techniques were used on admitted patients in well
      equipped hospitals. US was introduced in the 1970s as a safe, rapid, non-invasive
      and inexpensive technique and has been used for diagnosis in hospitals and
      screening in the fields. As a typical US image of the liver, septal formation by
      high echogenic bands like mosaic was described, and this network pattern was
      reported in the other endemic countries; China and Philippines. As an appropriate
      technique, US has been broadly used in developing countries. Not only for
      diagnosis in a hospital, but also for monitoring changes of morbidity, US is used
      in the community level. Network pattern related to the severity of S. japonicum
      infection, has not been described in S. mansoni or S. haematobium infection.
      Appearance of network pattern depends on pathological changes such as periportal
      fibrosis, postnecrotic fibrosis and calcified ova. For advanced studies on
      morbidity of schistosomiasis japonica, further research on pathological basis of
      network pattern and standardization of US diagnosis are necessary.

PMID- 14665398
TI  - Fixed-point observation of Oncomelania nosophora in Kofu Basin--establishment of
      monitoring system of schistosomiasis japonica in Japan.
AB  - There are still many Oncomelania snails that inhabit the Kofu Basin, Yamanashi
      Prefecture, Japan, which had been declared free of schistosomiasis japonica. Due
      to the need to monitor the situation, a fixed-point observation system using GIS
      from GPS is being examined. In addition, in broad present or former endemic
      areas, survey areas are being managed by remote sensing with satellite images or
      aerial photographs. A simple and effective monitoring method by mobile GIS using
      PDAs was developed, risk or hazard maps were prepared and a system that would
      enable a response in the event of reemergence is being examined.

PMID- 14665399
TI  - Cercariometry for detection of transmission sites for schistosomiasis.
AB  - Cercariometry provided information on diurnal fluctuation, seasonal and spatial
      distribution of cercariae in the suitable natural water bodies. There was an
      apparent mismatch between the results of cercariometry and snail sampling. Water,
      which cercariometry showed to contain cercariae was potentially infective,
      although the resultant worm load of sentinel rodents may not bear a linear
      relationship with cercarial density. Cercariometry has some weakness in practices
      and analysis of data, however, it provides the valuable information on the active
      transmission sites of schistosomiasis.

PMID- 14665400
TI  - Biological characteristics and control of intermediate snail host of Schistosoma
      japonicum.
AB  - Except for imported cases, we have had no new Schistosoma japonicum infection in
      Japan since 1977. But there are still two habitats of the intermediate snail
      host: Oncomelania nosophora in the previous endemic areas of Kofu Basin and
      Obitsu. O. nosophora from Kofu Basin and Obitsu are susceptible to Chinese and
      Philippine strains of S. japonicum. The number of immigrants from current endemic
      areas in China or the Philippines is increasing. In order to prevent re-emerging
      of S. japonicum infections in Japan, we should continue monitoring on those
      existing snail hosts and investigate an adequate quarantine system. In Japan,
      elimination of schistosomiasis has been mainly accomplished by control of the
      snail host. As measures of snail control, cement-lining of ditches and chemical
      mollusciciding were most effective in Japan. But the cost of this joint program
      is too expensive compared with health budget in almost developing countries. In
      endemic areas of Japan, land reformation from paddy field to fruit farm was also
      effective. The intermediate snail host in the Philippines, Oncomelania quadrasi
      is much more aquatic than O. nosophora. For control of O. quadrasi, small
      drainage of the water and land reclamation from swampy field to rice-field were
      effective. Based on biological characteristics of Oncomelania spp., we can modify
      the past successful snail control program in Japan to be adapted ecologically and
      economically to each endemic area of developing countries.

PMID- 14665401
TI  - Fungal morphology and metabolite production in submerged mycelial processes.
AB  - The use of fungi for the production of commercial products is ancient, but it has
      increased rapidly over the last 50 years. Fungi are morphologically complex
      organisms, differing in structure at different times in their life cycle,
      differing in form between surface and submerged growth, differing also with the
      nature of the growth medium and physical environment. Many genes and
      physiological mechanisms are involved in the process of morphogenesis. In
      submerged culture, a large number of factors contribute to the development of any
      particular morphological form. Factors affecting morphology include the type and
      concentration of carbon substrate, levels of nitrogen and phosphate, trace
      minerals, dissolved oxygen and carbon dioxide, pH and temperature. Physical
      factors affecting morphology include fermenter geometry, agitation systems,
      rheology and the culture modes, whether batch, fed-batch or continuous. In many
      cases, particular morphological forms achieve maximum performance. It is a very
      difficult task to deduce unequivocal general relationships between process
      variables, product formation and fungal morphology since too many parameters
      influence these interrelationships and the role of many of them is still not
      fully understood. The use of automatic image analysis systems during the last
      decade proved an invaluable tool for characterizing complex mycelial
      morphologies, physiological states and relationships between morphology and
      productivity. Quantified morphological information can be used to build
      morphologically structured models of predictive value. The mathematical modeling
      of the growth and process performance has led to improved design and operation of
      mycelial fermentations and has improved the ability of scientists to translate
      laboratory observations into commercial practice. However, it is still necessary
      to develop improved and new experimental techniques for understanding phenomena
      such as the mechanisms of mycelial fragmentation and non-destructive measurement
      of concentration profiles in mycelial aggregates. This would allow the
      establishment of a process control on a physiological basis. This review is
      focused on the factors influencing the fungal morphology and metabolite
      production in submerged culture.

PMID- 14665402
TI  - Production of polyhydroxyalkanoates by mixed culture: recent trends and
      biotechnological importance.
AB  - Polyhydroxyalkanoates (PHAs) are the polymers of hydroxyalkanoates that
      accumulate as carbon/energy or reducing-power storage material in various
      microorganisms. PHAs have been attracting considerable attention as biodegradable
      substitutes for conventional polymers. To reduce their production cost, a great
      deal of effort has been devoted to developing better bacterial strains and more
      efficient fermentation/recovery processes. The use of mixed cultures and cheap
      substrates can reduce the production cost of PHA. Accumulation of PHA by mixed
      cultures occurs under transient conditions mainly caused by intermittent feeding
      and variation in the electron donor/acceptor presence. The maximum capacity for
      PHA storage and the PHA production rate are dependent on the substrate and the
      operating conditions used. This work reviews the development of PHA research.
      Aspects discussed include metabolism and various mechanisms for PHA production by
      mixed cultures; kinetics of PHA accumulation and conversion; effects of carbon
      source and temperature on PHA production using mixed cultures; PHA production
      process design; and characteristics of PHA produced by mixed cultures.

PMID- 14665405
TI  - Activation of c-fos expression in the rat inferior olivary nucleus by ghrelin.
AB  - Ghrelin, a novel 28-amino-acid hormone secreted by gastric oxyntic glands,
      stimulates food intake and induces adiposity. We examined whether ghrelin
      activates the inferior olivary nucleus. Systemic administration of ghrelin (37
      nmol/kg) induced the expression of c-fos immunoreactivity in inferior olive
      neurons (n=6 rats). The number of neurons containing c-fos staining was
      significantly increased in the ghrelin-treated rats (65+/-14 vs.11+/-6 positive
      neurons, n=5). No significant difference in c-fos-positive neurons was observed
      between left (32+/-5) and right (33+/-6) inferior olivary nuclei. The number of c
      fos-positive neurons in rats with bilateral vagotomy was not significantly
      different from those with intact vagal nerves. The present study demonstrates
      that ghrelin induces c-fos expression in inferior olivary nucleus via a central
      mechanism.

PMID- 14665406
TI  - Two-minute rapid eye movement (REM) density fluctuations in human REM sleep.
AB  - Rapid eye movement (REM) density fluctuations during REM sleep were studied in
      five healthy young adults (23-26 years of age). Appropriate electro-oculographic
      (EOG) montage and automated EOG analysis enabled the detection of horizontal,
      vertical, and oblique REMs. REM density time series based on these REMs were
      formed for all the REM periods of the subjects. Autoregressive (AR) spectral
      analysis of the REM density time series estimated periodicities in the range of
      1.7-2.4 min for 14 of the 16 REM periods analyzed, regardless of duration or
      number of REMs. Four subjects had such periodicities in each of their REM periods
      and the fifth subject had such periodicities in half the REM periods. This REM
      density fluctuation at a periodicity of about 2 min may relate to an important
      'rhythmic' component of the REM generating mechanism(s).

PMID- 14665407
TI  - Magnetic mismatch fields elicited by vowel duration and pitch changes in Japanese
      words in humans: comparison between native- and non-speakers of Japanese.
AB  - Previous event-related brain potential research showed that mismatch negativity
      was elicited by phoneme contrasts in fluent second language (L2) learners, but
      not in non-speakers of L2. The present study tested whether the magnetic mismatch
      field (MMF) would be elicited in response to temporal and spectral changes in
      three Japanese synthesized words for both native- and non-speakers of Japanese.
      Magnetoencephalography responses were recorded with a dual 37-channel
      gradiometer. Unlike short-to-long vowel duration and falling-to-level pitch
      changes, long-to-short duration and level-to-falling pitch changes elicited a
      prominent MMF bilaterally for both groups, peaking at around 100 ms after change
      onset for duration and 200 ms for pitch. The MMF component is sensitive to vowel
      shortening rather than lengthening and to pitch falling rather than leveling.
      Automatic detection of changes in vowel shortening and pitch falling is a useful
      index of language-non-specific auditory memory traces.

PMID- 14665408
TI  - Recovery from fatigue: changes in local brain 2-[18F]fluoro-2-deoxy-D-glucose
      utilization measured by autoradiography and in brain monoamine levels of rat.
AB  - We recently established an animal model of fatigue in which rats were kept in a
      cage filled with water to a height of 1.5 cm for 5 days. In this way, after the
      fatigue session, they were returned to their home cage. Rats resting for 15 min
      or 2 h showed reduced 2-[18F]fluoro-2-deoxy-D-glucose uptake in their brain. Rats
      resting for 1 h showed a significantly increased ratio of 5-hydroxyindoleacetic
      acid/5-hydroxytryptamine, an index of serotonin turnover, in the frontal cortex,
      hippocampus, and cerebellum, and the ratio of [3,4-dihydroxyphenylacetic
      acid+homovanillic acid]/dopamine, an index of dopamine turnover, tended to be
      increased as compared with the control. These data suggest that improvement of
      glucose uptake and increased serotonergic and dopaminergic neuronal activities
      are associated with recovery from central fatigue.

PMID- 14665409
TI  - Reduced inflammatory mediator expression by pre-reperfusion infusion into
      ischemic territory in rats: a real-time polymerase chain reaction analysis.
AB  - The aim in this study was to investigate if our new experimental model for stroke
      therapy, flushing the ischemic territory with saline prior to reperfusion, could
      reduce overexpression of inflammatory mediators during reperfusion. Stroke in
      Sprague-Dawley rats (n=24) was induced by a 2-h middle cerebral artery occlusion
      using a novel intraluminal hollow filament. Prior to reperfusion, 12 of the
      ischemic rats received 6 ml isotonic saline at 37 degrees C infused into the
      ischemic area through the filament. Expression of interleukin-1beta (IL-1beta),
      tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule 1
      (ICAM-1) mRNA was analyzed by real-time reverse transcriptase-polymerase chain
      reaction (real-time RT-PCR). A significant overexpression (9-26 fold) of the
      genes encoding TNF-alpha, IL-1beta and ICAM-1 in ischemic rats was found during
      early reperfusion without flushing at 6 and 12 h. This increase was significantly
      reduced at both 6 and 12 h post-reperfusion as a result of saline flushing.

PMID- 14665410
TI  - Effect of chronic alcohol consumption on Go protein in rat brain.
AB  - Almost all of the important pathophysiological targets for ethanol in the nervous
      system appear to be specific membrane proteins involved in signal transduction.
      In this paper we have examined levels and functionality of the alpha subunit of
      the Go protein (Goalpha) in cerebral cortex and cerebellum from rats that have
      chronically ingested ethanol, by using immunoblotting and pertussis toxin
      catalyzed ADP-ribosylation experiments. Goalpha protein levels were increased in
      plasma membranes from the two brain areas, and this increase was shown to
      specifically affect Go1alpha, one of the two isoforms of the Goalpha subunit.
      Results obtained here lead us to suggest that increased Go1alpha in plasma
      membranes would counteract a modified and non-functional protein generated during
      chronic alcohol treatment.

PMID- 14665411
TI  - Perirhinal cortex relays auditory information to the frontal motor cortices in
      the rat.
AB  - Auditory evoked potentials (AEPs) were recorded in the motor cortices (MC) with
      chronically implanted electrodes in the rat. Some of the AEPs in the MC, namely
      negative potentials on the surface and positive ones at a depth of 2 mm at
      latencies of about 50-150 ms, were abolished by limited bilateral lesions of the
      anterior perirhinal cortex (PERa) which was responsive to auditory stimulus,
      indicating that the AEPs in the MC were at least partially relayed in the PERa.
      The auditory response in the MC was prominently enhanced when water was supplied
      or the medial forebrain bundle was stimulated after auditory stimulus. These
      results indicate that the MC receives the reward associated auditory information
      from the PERa.

PMID- 14665412
TI  - Phosphorylation of tau protein to sites found in Alzheimer's disease brain is
      catalyzed by Ca2+/calmodulin-dependent protein kinase II as demonstrated tandem
      mass spectrometry.
AB  - Neuronal Ca2+/calmodulin-dependent protein kinase II (CaMKII) is one of the most
      abundant protein kinases in the brain, and phosphorylates a broad range of
      substrate proteins. The phosphorylation of microtubule tau by CaMKII was
      investigated using tandem mass spectrometry (MS/MS). Recombinant human tau was
      phosphorylated at Thr212, Ser214, Ser262, and Ser356 by CaMKII. The
      phosphorylation of these sites is found in paired helical filament (PHF)-tau. In
      addition to these sites, Ser131 and Thr135 were phosphorylated by CaMKII.
      Phosphorylation at Ser131, Thr135, Thr212 and Ser214 by CaMKII has not been
      reported previously. Thr212 and Ser214 are in the consensus phosphorylation
      sequence of CaMKII (RXXS/T), and non-fetal-type phosphorylation sites of tau. Non
      fetal-type phosphorylation may produce PHF-tau. These results suggested that
      CaMKII is involved in the phosphorylation of tau in Alzheimer's disease brain.

PMID- 14665413
TI  - Localization of mechanosensitive channel TRPV4 in mouse skin.
AB  - A transient receptor potential (TRP) family, TRPV4, is a calcium-permeable swell
      activated channel, playing a role in cutaneous mechanosensation. To elucidate the
      localization in the mechanosensitive endings, we found with immunohistochemistry
      in mice that TRPV4 was expressed both by small (low threshold) and large (high
      threshold) dorsal root ganglia neurons. In addition to free nerve endings, TRPV4
      was specifically located at cutaneous mechanosensory terminals co-localized with
      neurofilament 200, including Meissner, Merkel, penicillate and intraepidermal
      terminals but not including hair follicle palisades. The distribution suggests
      that the sensation of pressure by mechanosensitive TRPV4 channel is transmitted
      through A- as well as C-fiber.

PMID- 14665414
TI  - Sensitivity of human EEG alpha band desynchronization to different working memory
      components and increasing levels of memory load.
AB  - Event-related alpha band desynchronization is frequently used to analyze
      spatiotemporal cortical activation patterns during the performance of cognitive
      tasks. In the present paper the sensitivity of alpha band desynchronization to
      increasing levels of cognitive load and to different cognitive working memory
      components is investigated. A 27-channel electroencephalogram of 62 participants
      while solving (a) a short-term memory and (b) a working memory task (dual task),
      each with five levels of memory load, was analyzed. We found (a) a linearly
      increasing desynchronization in the upper alpha band with ascending cognitive
      load, and (b) evidence of the involvement of distinguishable cognitive components
      (storage and controlled attention) in the memory tasks.

PMID- 14665415
TI  - Control of postganglionic sympathetic efferent fibers by neurokinin 1 receptors
      in rats.
AB  - Substance P (SP) is released peripherally from nociceptive terminals and has a
      direct effect on vascular cells. The present study suggests an indirect effect as
      well. In normal rats and rats with one hindpaw inflamed for 48 h following
      intraplantar injection of complete Freund's adjuvant, neurokinin 1 (NK1)
      receptors were immunohistochemically localized on postganglionic sympathetic
      axons. The percentage of NK1-labeled axons in the gray rami from normal rats was
      35.0+/-5.0; in inflamed rats this percentage increased significantly to 49.1+/
      2.3. These data suggest a sensory-sympathetic reflex, where SP activates these
      peripheral sympathetic receptors with subsequent release of noradrenaline and
      other compounds to affect vascular cells indirectly. This control is enhanced
      after inflammation.

PMID- 14665416
TI  - Association between small apolipoprotein(a) isoforms and frontotemporal dementia
      in humans.
AB  - Apolipoprotein(a) [apo(a)] is a genetically polymorphic glycoprotein that has
      several similarities to apolipoprotein E. However, its role as a risk factor for
      frontotemporal dementia (FTD) remains to be elucidated. We therefore investigated
      the effect of an apo(a) polymorphism on the incidence of FTD in a sample of
      Caucasian Italian patients. From the entire group of FTD patients (n=54), 55.6%
      of the subjects had at least one apo(a) low molecular weight (MW) isoform,
      compared to 29.9% of non-demented controls (n=77). The difference between the two
      groups was statistically significant (odds ratio 2.93, 95% confidence interval
      1.42-6.06, P=0.003). The FTD group was further divided into sporadic (n=26) and
      familial (n=28) cases. Even after such dichotomization, both sporadic and
      familial FTD patients showed a significantly higher prevalence of low MW apo(a)
      isoforms than the cognitively healthy controls (P=0.011 and P=0.025,
      respectively). Our data suggest a role of apo(a) phenotypes of low MW in
      mediating susceptibility to FTD.

PMID- 14665417
TI  - NG-nitro-L-arginine methyl ester-induced norepinephrine release from cardiac
      sympathetic nerve endings in anesthetized cats.
AB  - Using the cardiac dialysis technique in the anesthetized cat, we examined the
      effects of NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide (NO) synthase
      inhibitor, 100 mM) on sympathetic modulation. Local administration of L-NAME
      induced increases in dialysate norepinephrine (NE) levels, which were not
      affected by the addition of omega-conotoxinGVIA. High-potassium (high K+)-evoked
      increases in dialysate NE levels were suppressed by addition of L-NAME. To
      confirm the involvement of NO in the NE releasing action, we compared dialysate
      NE levels during the administration of L-NAME or D-NAME and no significant
      differences between them. L-NAME induces spontaneous non-exocytotic NE release
      but suppresses exocytotic NE release by high K+. L-NAME may interact with both NE
      transport and NE release mechanisms. However, NO may contribute little to the
      amounts of NE released by L-NAME.

PMID- 14665418
TI  - p38 MAP kinase mediates bilirubin-induced neuronal death of cultured rat
      cerebellar granule neurons.
AB  - Brain damage induced by unconjugated bilirubin, the end product of heme
      catabolism, in human neonates is a well recognized clinical syndrome. However,
      the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain
      unclear. To characterize the sequence of events leading to bilirubin-induced
      neurotoxicity, we have exposed rat cerebellar granule neurons (CGN) to bilirubin
      and investigated whether activation of p38 MAP kinase mediates neuronal death. In
      this study, bilirubin markedly induces an early activation of p38 MAP kinase at 1
      h. Pretreatment of neurons with a p38 MAP kinase inhibitor, SB 203580,
      significantly protected CGN against bilirubin-induced neurotoxicity. Our data
      suggest that hyperphosphorylation of p38 MAP kinase plays an important role in
      bilirubin-induced neuronal death and provides a novel approach to discovering
      drugs to treat bilirubin-induced encephalopathy.

PMID- 14665419
TI  - Strain differences in pain sensitivity and expression of preprodynorphin mRNA in
      rats following peripheral inflammation.
AB  - The experience of pain is highly variable among individuals, which may be due in
      part to the effects of genetic factors on the central transmission and modulation
      of noxious inputs. This study examined behavioral responses and the expression of
      preprodynorphin (PPD) mRNA at the spinal level during complete Freund's adjuvant
      induced inflammation of the unilateral hind paw in male Fischer 344 (F344),
      Sprague-Dawley (SD), and Lewis (LEW) rats. Experiments showed that F344 rats
      exhibited stronger hind paw hyperalgesia and greater spinal PPD mRNA induction
      than SD or LEW rats. These results indicate that genetic factors that determine
      the spinal PPD mRNA and dynorphin production underlie strain-dependent
      differences in pain perception.

PMID- 14665420
TI  - Microvascular basal lamina damage in thromboembolic stroke in a rat model.
AB  - We investigated microvascular damage in areas with magnetic resonance imaging
      (MRI)-defined apparent diffusion coefficient reduction (ADC-R) in a rat model of
      thromboembolic occlusion of the middle cerebral artery. Rats received either
      intracarotid recombinant tissue plasminogen activator (rt-PA) or saline.
      Microvascular basal lamina damage was quantified by immunohistochemical staining
      of collagen type IV and by videoimaging analysis. ADC-R positive basal ganglia
      (cortical) areas showed a significant reduction of stained microvascular area by
      15+/-6% (8+/-7%) and the microvascular density by 13+/-5% (8+/-6%) of that on the
      non-ischemic control side (P<0.001). There were no significant microvascular
      differences between rats given rt-PA or saline, or between those with or without
      angiographically proven recanalization. This study reports for the first time
      that microvascular basal lamina damage in experimental thromboembolic stroke is
      confined to regions with ADC-R in MRI.

PMID- 14665421
TI  - Amyotrophic lateral sclerosis patient IgG alters voltage dependence of Ca2+
      channels in dissociated rat motoneurons.
AB  - Previous studies on sporadic amyotrophic lateral sclerosis (SALS) have detected
      IgG within motoneurons of patients and these IgGs have been shown to alter
      voltage dependent calcium channel activity in various cell types. The current
      study investigates whether IgG from categorized SALS patients alter voltage
      dependent calcium currents in rat motoneurons in culture. Patients were
      categorized based on onset and progression pattern. IgG yields were 38% higher in
      SALS patients compared to control subjects. Incubation with 1 mg/ml IgG from SALS
      patients did not cause visible toxicity, alter input resistance, capacitance or
      the maximal calcium conductance in rat motoneurons when compared to motoneurons
      incubated with control IgG. However, the activation curve of calcium current was
      shifted to the left in motoneurons treated with SALS IgG compared to control IgG.

PMID- 14665422
TI  - Mutant presenilin 1 proteins induce cell death and reduce tau-dependent processes
      outgrowth.
AB  - The expression of familial Alzheimer's disease mutants of presenilin-1 (PS1)
      proteins has been observed to induce cell death in cellular systems. To
      investigate how this phenomenon might be associated to alterations of the
      microtubule network, we have studied the effect of wild-type and mutant (C263R,
      P264L and delta9) PS1 proteins expression on the formation of microtubule
      dependent processes outgrowth and the association of PS1 to the insoluble
      cytoskeletal fraction in a cell line expressing the tau microtubule-associated
      protein. Expression of wild-type and mutant PS1 was associated with increased
      cell death, most marked for the P264L and delta9 mutants. The three PS1 mutants
      induced a significant reduction of the length of cell processes. These effects
      were not associated to a change in tau phosphorylation. However, the mutant PS1
      proteins increased the proportion of insoluble tau in the cytoskeletal fraction
      and they were concentrated in the same fraction. These results suggest that PS1
      proteins interact with the microtubule network, affect its organization and that
      this phenomenon, more marked for the PS1 mutants, might play a role in the cell
      dysfunction induced by mutant PS1 proteins.

PMID- 14665423
TI  - Immobility from administration of the alpha1-adrenergic antagonist, terazosin, in
      the IVth ventricle in rats.
AB  - Brain alpha1-adrenoceptors have been shown to be essential for motor activity and
      movement in mice using intraventricular injection of alpha1-antagonists. To
      facilitate subsequent neuroanatomical mapping of these receptors, the present
      study was undertaken to replicate these effects in the rat. Rats were
      administered the alpha1-antagonist, terazosin, in the absence and presence of the
      alpha1-agonist, phenylephrine, in the IVth ventricle and were tested for their
      motor activity responses to an environmental change. Terazosin was found to
      produce a dose-dependent, virtually complete cessation of behavioral activity
      that was reversed by coinfusion of phenylephrine. The results could not be
      explained by sedation. It is concluded that central alpha1-adrenoceptors are
      essential for behavioral activation in rats as in mice.

PMID- 14665424
TI  - Unmet need and unintended fertility: longitudinal evidence from upper Egypt.
AB  - CONTEXT: Although unmet need for family planning is a standard measure for
      evaluating programs' effectiveness in meeting the reproductive needs of
      individuals, its validity and accuracy in identifying women most at risk of
      unintended pregnancy have been questioned. METHODS: Women who participated in the
      1995 Egypt Demographic and Health Survey in two governorates in Upper Egypt
      (Assuit and Souhag) were followed for two years (N=2,444); in-depth data on their
      fertility preferences, contraceptive use and births were gathered in 1996 and
      1997. Transitions among contraceptive need categories from 1995 to 1997 are
      examined, and rates of unintended (mistimed and unwanted) births are calculated
      according to contraceptive need status at baseline. RESULTS: In the aggregate,
      unmet need increased by six percentage points, from 28% to 34%. This change was
      the net outcome of 14% moving out of unmet need and 20% moving into unmet need
      (i.e., substantial satisfaction of unmet need was offset by increased demand for
      contraception). The rate of unintended fertility was far higher among women with
      unmet need at baseline than among contraceptive users in 1995. Women with unmet
      need made up about one-quarter of the baseline sample, but they contributed
      almost one-half of mistimed and unwanted births during the two years. The
      majority of unintended births were to women who had never practiced
      contraception, whereas fewer than one-fifth were to women with recent
      contraceptive experience (including contraceptive failure). CONCLUSIONS: : Unmet
      need for family planning remains a useful tool for identifying and targeting
      women at high risk of unintended pregnancy.

PMID- 14665425
TI  - Using network analysis to understand community-based programs: a case study from
      highland Madagascar.
AB  - CONTEXT: Programs using community-based distribution (CBD) of family planning
      services have had mixed success in Sub-Saharan Africa. Knowledge about why these
      programs succeed or fail is limited. METHODS: In 1999, a total of 159 women and
      men of reproductive age were interviewed in a village in highland Madagascar with
      an active community-based family planning program. Network analysis informed by
      chi-square tests and multiple regression analysis was used to test whether
      respondents' communication with CBD agents and the location of their discussion
      partners were associated with their knowledge and use of family planning.
      RESULTS: The CBD agents were highly central in the village's family planning
      network; 35% of women and 19% of men directly communicated with a CBD agent about
      family planning or were indirectly linked to an agent. Knowledge of family
      planning was associated with having either a direct or an indirect link to a CBD
      agent; use of a modern method was associated with discussing family planning only
      with someone outside the village (odds ratio, 12.6) or with discussing it in the
      village and communicating directly with a CBD agent (10.8). CONCLUSIONS: Network
      analysis can improve the understanding of community-based program functioning by
      providing a way to examine who receives information from and is influenced by CBD
      agents.

PMID- 14665426
TI  - The psychosocial context of young adult sexual behavior in Nicaragua: looking
      through the gender lens.
AB  - CONTEXT: Understanding the nature and magnitude of gender differences in sexual
      norms among young adults in Nicaragua, and how these differences affect sexual
      behavior, is important for the design of reproductive health programs. METHODS: A
      representative cross-sectional survey was conducted in six departments in the
      Pacific region of Nicaragua in 1998. A total of 552 never-married women and 289
      never-married men aged 15-24 were interviewed about their perceptions of social
      pressure to engage in premarital sex; perceived social approval of and attitudes
      toward premarital sex and premarital pregnancy; perceived sexual activity among
      peers and siblings; communication with parents on sexuality issues; the
      psychosocial context of sexual debut; and preferred sources of information on
      sexuality issues. RESULTS: Most young men (83%) reported that they had received
      direct encouragement from at least one person in the last year to engage in
      premarital sex, and at least half perceived that their father, siblings, other
      relatives and friends approved of premarital intercourse. A significantly greater
      proportion of men than of women reported that curiosity or gaining experience
      motivated their sexual debut (61% vs. 21%). Men perceived themselves to have a
      higher risk of unplanned and unprotected sex than did women. In contrast, women
      held more negative attitudes toward premarital sex and were more often
      discouraged by parents or siblings from engaging in sex. CONCLUSIONS:
      Reproductive health programs for young Nicaraguans need to address gender-based
      double standards, which raise the risk of unplanned, unprotected sex and
      unintended pregnancy.

PMID- 14665427
TI  - Where do rural women obtain postabortion care? The case of Uttar Pradesh, India.
AB  - CONTEXT: Although Indian law permits abortion for a broad range of social and
      medical indications, millions of unsafe and illegal abortions and countless
      subsequent complications occur annually. Nonetheless, in the central Indian state
      of Uttar Pradesh, few women with abortion complications are reported to seek care
      at registered private and public health facilities. Information is needed about
      where rural women seek care for abortion complications and about the quality of
      care they receive. METHODS: Qualitative data were collected in 1999 in four
      villages in rural Uttar Pradesh. The study team conducted community mapping
      exercises, focus group discussions with female and male community members, and in
      depth interviews with women of reproductive age and with postabortion care
      providers. RESULTS: Postabortion care is widely available in the villages
      studied, largely from untrained or inappropriately trained providers. Because
      village-level providers are the front line of care for many women, abortion
      complications may be exacerbated rather than alleviated, appropriate care delayed
      and the cost of treatment increased. Village-level postabortion care does not
      include family planning and contraceptive counseling services or links to
      reproductive and other health services. CONCLUSIONS: : Existing village-level
      postabortion care services are inadequate. There is an urgent need to increase
      women's access to higher-quality postabortion care. This can be done by
      simultaneously engaging village-level providers in the formal system of
      postabortion care service delivery, as appropriate, and addressing the prevailing
      social and cultural mores that discourage women with abortion complications from
      seeking higher-level care.

PMID- 14665428
TI  - The standard days method of family planning: a response to Cairo.

PMID- 14665429
TI  - Vascular localization of soluble epoxide hydrolase in the human kidney.
AB  - Epoxyeicosatrienoic acids are cytochrome P-450 metabolites of arachidonic acid
      with multiple biological functions, including the regulation of vascular tone,
      renal tubular transport, cellular proliferation, and inflammation.
      Epoxyeicosatrienoic acids are converted by soluble epoxide hydrolase into the
      corresponding dihydroxyeicosatrienoic acids, and epoxyeicosatrienoic acid
      hydration is regarded as one mechanism whereby their biological effects are
      eliminated. Previous animal studies indicate that soluble epoxide hydrolase plays
      an important role in the regulation of renal eicosanoid levels and systemic blood
      pressure. To begin to elucidate the mechanism of these effects, we determined the
      cellular localization of soluble epoxide hydrolase in human kidney by examining
      biopsies taken from patients with a variety of non-end-stage renal diseases, as
      well as those without known renal disease. Immunohistochemical staining of
      acetone-fixed kidney biopsy samples revealed that soluble epoxide hydrolase was
      preferentially expressed in the renal vasculature with relatively low levels in
      the surrounding tubules. Expression of soluble epoxide hydrolase was evident in
      renal arteries of varying diameter and was localized mostly in the smooth muscle
      layers of the arterial wall. Western blot analysis and functional assays
      confirmed the expression of soluble epoxide hydrolase in the human kidney. There
      were no obvious differences in soluble epoxide hydrolase expression between
      normal and diseased human kidney tissue in the samples examined. Our results
      indicate that soluble epoxide hydrolase is present in the human kidney, being
      preferentially expressed in the renal vasculature, and support an essential role
      for this enzyme in renal hemodynamic regulation and its potential utility as a
      target for therapeutic intervention.

PMID- 14665430
TI  - Gene expression alterations during HGF-induced dedifferentiation of a renal
      tubular epithelial cell line (MDCK) using a novel canine DNA microarray.
AB  - Hepatocyte growth factor (HGF) elicits a broad spectrum of biological activities,
      including epithelial cell dedifferentiation. One of the most widely used and best
      studied polarized epithelial cell lines is the Madin-Darby canine kidney (MDCK)
      cell line. Here, we describe and validate the early response of polarized
      monolayers of MDCK cells stimulated with recombinant HGF using a novel canine DNA
      microarray designed to query 12,473 gene sequences. In our survey, eight genes
      previously implicated in the HGF signaling pathway were differentially regulated,
      demonstrating that the system was responsive to HGF. Also identified were 117
      genes not previously known to be involved in the HGF pathway. The results were
      confirmed by real-time PCR or Western blot analysis for 38 genes. Of particular
      interest were the large number of differentially regulated genes encoding small
      GTPases, proteins involved in endoplasmic reticulum translation, proteins
      involved in the cytoskeleton, the extracellular matrix, and the hematopoietic and
      prostaglandin systems.

PMID- 14665431
TI  - Preservation of complex I function during hypoxia-reoxygenation-induced
      mitochondrial injury in proximal tubules.
AB  - Inhibition of complex I has been considered to be an important contributor to
      mitochondrial dysfunction in tissues subjected to ischemia-reperfusion. We have
      investigated the role of complex I in a severe energetic deficit that develops in
      kidney proximal tubules subjected to hypoxia-reoxygenation and is strongly
      ameliorated by supplementation with specific citric acid cycle metabolites,
      including succinate and the combination of -ketoglutarate plus malate. NADH:
      ubiquinone reductase activity in the tubules was decreased by only 26% during 60
      min hypoxia and did not change further during 60-min reoxygenation. During
      titration of complex I activity with rotenone, progressive reduction of NAD+ to
      NADH was detected at >20% complex I inhibition, but substantial decreases in ATP
      levels and mitochondrial membrane potential did not occur until >70% inhibition.
      NAD+ was reduced to NADH during hypoxia, but the NADH formed was fully reoxidized
      during reoxygenation, consistent with the conclusion that complex I function was
      not limiting for recovery. Extensive degradation of cytosolic and mitochondrial
      NAD(H) pools occurred during either hypoxia or severe electron transport
      inhibition by rotenone, with patterns of metabolite accumulation consistent with
      catabolism by both NAD+ glycohydrolase and pyrophosphatase. This degradation was
      strongly blocked by alpha-ketoglutarate plus malate. The data demonstrate
      surprisingly little sensitivity of these cells to inhibition of complex I and
      high levels of resistance to development of complex I dysfunction during hypoxia
      reoxygenation and indicate that events upstream of complex I are important for
      the energetic deficit. The work provides new insight into fundamental aspects of
      mitochondrial pathophysiology in proximal tubules during acute renal failure.

PMID- 14665432
TI  - Ca2+ uptake in mitochondria occurs via the reverse action of the Na+/Ca2+
      exchanger in metabolically inhibited MDCK cells.
AB  - In ischemic or hypoxic tissues, elevated Ca2+ levels have emerged as one of the
      main damaging agents among other Ca2+-independent mechanisms of cellular injury.
      Because mitochondria, besides the endoplasmic reticulum, play a key role in the
      maintainance of cellular Ca2+ homeostasis, alterations in the mitochondrial Ca2+
      content ([Ca2+]m) were monitored in addition to changes in cytosolic Ca2+
      concentration ([Ca2+]i) during metabolic inhibition (MI) in renal epithelial
      Madin-Darby canine kidney (MDCK) cells. [Ca2+]i and [Ca2+]m were monitored via,
      respectively, fura 2 and rhod 2 measurements. MI induced an increase in [Ca2+]i
      reaching 631+/-78 nM in approximately 20 min, followed by a decrease to 118+/-9
      nM in the next approximately 25 min. A pronounced drop in cellular ATP levels and
      a rapid increase in intracellular Na+ concentrations in the first 20 min of MI
      excluded Ca2+ efflux in the second phase via plasma membrane ATPases or Na+/Ca2+
      exchangers (NCE). Mitochondrial rhod 2 intensities increased to 434+/-46% of the
      control value during MI, indicating that mitochondria sequester Ca2+ during MI.
      The mitochondrial potential (deltapsim) was lost in 20 min of MI, excluding
      mitochondrial Ca2+ uptake via the deltapsim-dependent mitochondrial Ca2+
      uniporter after 20 min of MI. Under Na+-free conditions, or when CGP-37157, a
      specific inhibitor of the mitochondrial NCE, was used, no drop in [Ca2+]i was
      seen during MI, whereas the MI-induced increase in mitochondrial rhod 2
      fluorescence was strongly reduced. To our knowledge, this study is the first to
      report that in metabolically inhibited renal epithelial cells mitochondria take
      up Ca2+ via the NCE acting in the reverse mode.

PMID- 14665433
TI  - Functional caveolae are a prerequisite for CD40 signaling in human renal proximal
      tubule cells.
AB  - The role of caveolae in CD40/CD154 activation of proinflammatory chemokines and
      their potential role in renal inflammatory disease were explored in primary
      cultures of human renal proximal tubule epithelial cells. With the use of a cell
      fractionation assay, caveolin-1 (Cav-1), the defining structural protein of
      caveolae, was detected exclusively in the cell membrane (detergent insoluble)
      component of resting and CD40-activated cells. In the unstimulated condition,
      CD40 was associated with Cav-1, and with activation of the receptor by its
      cognate ligand CD154, CD40 disassociated from Cav-1. Other previously identified
      components of the CD40 signaling pathway, namely, SAPK/JNK, p38, and ERK1/2
      MAPKs, but not tumor necrosis factor receptor-associated factor 6 (TRAF-6), were
      also present within caveolae and dissociated from this structure with ligation of
      the CD40 receptor. Disruption of caveolae with filipin diminished CD40-mediated
      MAPK activation and blunted downstream monocyte chemoattractant protein-1 (MCP-1)
      and IL-8 production. Similarly, dislodgment of signaling proteins from their
      scaffolding with a peptide targeted to the Cav-1 scaffolding domain (CSD)
      resulted in blunted MAPK activation and augmented IL-8 and MCP-1 production. In
      contrast, epidermal growth factor (EGF)-mediated tyrosine phosphorylation of the
      EGF receptor and activation of ERK1/2 were not interrupted by the peptide. We
      conclude that in human renal proximal tubule epithelial cells, CD40 and its
      downstream MAPK signaling proteins are located in membrane rafts and that
      disruption of caveolae or dislodgment of signaling proteins from the CSD
      diminishes MAPK activation and IL-8 and MCP-1 production in these cells.

PMID- 14665434
TI  - p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression
      in podocytes: implications for the actin cytoskeleton.
AB  - A dynamic cytoskeleton allows podocytes to withstand significant mechanical
      stress on elevation of intraglomerular capillary pressure (Pgc). However,
      vasoactive hormones, such as prostaglandin E2 (PGE2), may challenge the integrity
      of the actin cytoskeleton, alter podocyte morphology, and compromise glomerular
      permeability. PGE2 synthesis correlates with the onset of proteinuria and
      increased Pgc following reduced nephron mass. We investigated the interplay among
      mechanical stress, cyclooxygenase (COX), E-prostanoid (EP) receptor expression,
      and the actin cytoskeleton, using an in vitro model of cell stretch. Immortalized
      mouse podocytes grown on flexible silicone membranes were cyclically stretched
      (5% elongation, 0.5 Hz) for 2 h. EP4 and COX-2 mRNA increased three- and
      sevenfold above nonstretched controls, whereas EP1 and COX-1 levels were
      unchanged. Six hours of stretch resulted in a threefold increase in PGE2
      stimulated cAMP accumulation, a measure of EP4 receptor function, and an increase
      in COX-2 protein. The stretch-induced effects on COX-2/EP4 expression and EP4
      induced cAMP production were attributable to p38 MAP kinase, as blockade of this
      pathway, but not of ERK or JNK, abrogated the response. These stretch-induced
      changes in expression were transcriptionally dependent as they were actinomycin D
      sensitive. Finally, we investigated the influence of enhanced EP4 signaling on
      the actin cytoskeleton. Addition of PGE2 resulted in actin filament
      depolymerization observable only in stretched cells. Our results indicate that
      key components of the eicosanoid pathway are upregulated by mechanically
      stimulated p38 MAP kinase in podocytes. Enhanced EP4 receptor signaling may
      undermine podocyte cytoskeletal dynamics and thereby compromise filtration
      barrier function under conditions of increased Pgc.

PMID- 14665435
TI  - Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to
      bladder colonization by type 1-fimbriated Escherichia coli.
AB  - The adhesion of uropathogenic Escherichia coli to the urothelial surface of the
      bladder is a prerequisite for the establishment of bladder infections. This
      adhesion process relies on E. coli adhesins and their cognate urothelial
      receptors, and it also is influenced by an intricate array of defense mechanisms
      of the urinary system. In this study, we examined the in vivo role of Tamm
      Horsfall protein (THP), the most abundant urinary protein, in innate urinary
      defense. We genetically ablated the mouse THP gene and found that THP deficiency
      predisposes mice to bladder infections by type 1-fimbriated E. coli. Inoculation
      of too few type 1-fimbriated E. coli to colonize wild-type mice caused
      significant bladder colonization in THP-knockout mice. In contrast, THP
      deficiency did not enhance the ability of P-fimbriated E. coli to colonize the
      bladder. Our results provide the first in vivo evidence indicating that under
      physiological conditions, the mannosylated THP can serve as an effective soluble
      "receptor," binding to the type 1-fimbriated E. coli and competitively inhibiting
      them from adhering to the uroplakin Ia receptors present on the urothelial
      surface. These results suggest that potential THP defects, either quantitative or
      qualitative, could predispose the urinary bladder to bacterial infections. The
      generation of THP-deficient mice established the role of THP as a first line of
      urinary defense and should help elucidate other potential functions of this major
      protein in urinary tract physiology and diseases.

PMID- 14665437
TI  - Gastrointestinal satiety signals I. An overview of gastrointestinal signals that
      influence food intake.
AB  - An overview is presented of those signals generated by the gastrointestinal (GI)
      tract during meals that interact with the central nervous system to create a
      sensation of fullness and satiety. Although dozens of enzymes, hormones, and
      other factors are secreted by the GI tract in response to food in the lumen, only
      a handful are able to influence food intake directly. Most of these cause meals
      to terminate and hence are called satiety signals, with CCK being the most
      investigated. Only one GI signal, ghrelin, that increases meal size has been
      identified. The administration of exogenous CCK or other satiety signals causes
      smaller meals to be consumed, whereas blocking the action of endogenous CCK or
      other satiety signals causes larger meals to be consumed. Satiety signals are
      relayed to the hindbrain, either indirectly via nerves such as the vagus from the
      GI tract or else directly via the blood. Most factors that influence how much
      food is eaten during individual meals act by changing the sensitivity to satiety
      signals. This includes adiposity signals as well as habits and learning, the
      social situation, and stressors.

PMID- 14665438
TI  - Mild irritant prevents ethanol-induced gastric mucosal microcirculatory
      disturbances through actions of calcitonin gene-related peptide and PGI2 in rats.
AB  - Pretreatment with a mild irritant such as 1 M NaCl prevented ethanol-induced
      mucosal injury, which was abolished by indomethacin, suggesting involvement of
      endogenous PGs. With the use of intravital microscopy, we investigated the
      mechanism in microcirculation whereby a mild irritant prevents ethanol-induced
      mucosal injury. Microcirculation of the basal part of gastric mucosa in
      anesthetized rats was observed through a window with transillumination. Diameters
      of arterioles, collecting venules, and venules were measured with an electric
      microscaler. One molar NaCl alone caused dilation of arterioles and constrictions
      of collecting venules and venules, which were inhibited by indomethacin. Ethanol
      (50%) applied to mucosa constricted collecting venules and venules but dilated
      arterioles. Constriction of collecting venules resulted in mucosal congestion.
      Pretreatment with 1 M NaCl inhibited ethanol-induced constrictions of collecting
      venules and venules, and administration of indomethacin or a calcitonin gene
      related peptide (CGRP) antagonist, CGRP-(8-37), abolished elimination of
      constrictions. Topical application (1 nM-10 microM) of PGE2 or beraprost sodium
      (a PGI2 analog) to microvasculature markedly and dose-dependently dilated
      arterioles, whereas that of PGE2, but not beraprost, slightly constricted
      collecting venules. Pretreatment of microvasculature with a nonvasoactive
      concentration of PGE2 (100 nM) or beraprost (1 nM) completely inhibited ethanol
      induced constriction of collecting venules. The inhibitory effect of beraprost
      but not of PGE2 was abolished by CGRP-(8-37). Present results suggest that the
      mechanism whereby 1 M NaCl prevents ethanol-induced injury is elimination of
      constrictions of collecting venules and venules by CGRP whose release may be
      enhanced by PGI2 but not by PGE2.

PMID- 14665439
TI  - Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2
      inhibitors to aggravate gastric damage and inflammation.
AB  - Aceylation of cyclooxygenase (COX)-2 by aspirin can trigger the formation of
      15(R)-epilipoxin A4, or aspirin-triggered lipoxin (ATL). ATL exerts protective
      effects in the stomach. Selective COX-2 inhibitors block ATL synthesis and
      exacerbate aspirin-induced gastric damage. Nitric oxide-releasing aspirins,
      including NCX-4016, have antiplatelet effects similar to aspirin but do not cause
      gastric damage. In the present study, we examined whether or not NCX-4016
      triggers ATL synthesis and/or upregulates gastric COX-2 expression and the
      effects of coadministration of NCX-4016 with a selective COX-2 inhibitor on
      gastric mucosal injury and inflammation. Rats were given aspirin or NCX-4016
      orally and either vehicle or a selective COX-2 inhibitor (celecoxib)
      intraperitoneally. Gastric damage was blindly scored, and granulocyte
      infiltration into gastric tissue was monitored through measurement of
      myeloperoxidase activity. Gastric PG and ATL synthesis was measured as was COX-2
      expression. Whereas celecoxib inhibited gastric ATL synthesis and increased the
      severity of aspirin-induced gastric damage and inflammation, coadministration of
      celecoxib and NCX-4016 did not result in damage or inflammation. NCX-4016 did not
      upregulate gastric COX-2 expression nor did it trigger ATL synthesis (in contrast
      to aspirin). Daily administration of aspirin for 5 days resulted in significantly
      less gastric damage than that seen with a single dose, as well as augmented ATL
      synthesis. Celecoxib reversed this effect. In contrast, repeated administration
      of NCX-4016 failed to cause gastric damage, whether given alone or with
      celecoxib. These studies support the notion that NCX-4016 may be an attractive
      alternative to aspirin for indications such as cardioprotection, including in
      individuals also taking selective COX-2 inhibitors.

PMID- 14665440
TI  - Paradoxical roles of different nitric oxide synthase isoforms in colonic injury.
AB  - Nitric oxide (NO) is a free radical that is largely produced by three isoforms of
      NO synthase (NOS): neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). NO
      regulates numerous processes in the gastrointestinal tract; however, the overall
      role that NO plays in intestinal inflammation is unclear. NO is upregulated in
      both ulcerative colitis and Crohn's disease as well as in animal models of
      colitis. There have been conflicting reports on whether NO protects or
      exacerbates injury in colitis or is simply a marker of inflammation. To determine
      whether the site, timing, and level of NO production modulate the effect on the
      inflammatory responses, the dextran sodium sulfate model of colitis was assessed
      in murine lines rendered deficient in iNOS, nNOS, eNOS, or e/nNOS by targeted
      gene disruption. The loss of nNOS resulted in more severe disease and increased
      mortality, whereas the loss of eNOS or iNOS was protective. Furthermore,
      concomitant loss of eNOS reversed the susceptibility found in nNOS-/- mice.
      Deficiencies in specific NOS isoforms led to distinctive alterations of
      inflammatory responses, including changes in leukocyte recruitment and
      alterations in colonic lymphocyte populations. The present studies indicate that
      NO produced by individual NOS isoforms plays different roles in modulating an
      inflammatory process.

PMID- 14665441
TI  - Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity
      in differentiating osteoblasts.
AB  - The insulin-like growth factor (IGF) system plays an important role in the
      autocrine and paracrine regulation of bone formation and remodeling. The aim of
      this study was to evaluate the role of the autocrine IGF system during osteogenic
      differentiation in rat tibial osteoblasts (ROB) in culture. In this in vitro
      model, the stages of osteogenesis studied were S1, corresponding to the onset of
      alkaline phosphatase (AP) expression (days 0-3); S2, coincident with the peak of
      AP expression in differentiation culture conditions (days 4-6), and S3,
      corresponding to the onset of mineral deposition in the extracellular matrix
      (days 7-9). The results showed that conditioned medium of ROB contains greater
      amounts of IGF-II than IGF-I at all differentiation stages. Both peptides showed
      the highest concentrations on day 3 of differentiation (end of S1). All IGF
      binding proteins (IGFBPs), except IGFBP-1 and -6, were detected, and IGFBP-2 was
      the most abundant IGFBP present in the conditioned media, and its degradation
      increased from S1 to S3. By semiquantitative RT-PCR, IGF-I and IGF-II were highly
      expressed on days 3 and 6, whereas IGFBP-2 was constantly expressed. We focused
      our study on the role of IGF-II and IGFBP-2 on the synthesis of AP, an early
      marker of osteoblast maturation. The results showed that a significant increase
      in AP expression was induced by IGF-II added to the differentiating osteoblasts
      continuously or in S1 but not in S2 or S3. IGFBP-2 was able to potentiate
      endogenous and exogenous IGF-II-dependent stimulation of AP activity, and its
      proteolytic degradation in late stages of osteogenesis (S2 and S3) was highly
      correlated with the increase of active matrix metalloproteinase-2 in the CM and
      with the decreased efficacy of IGF-II action. These data suggest that IGFBP-2, at
      nearly equimolar concentration with IGF-II, plays a potentiating role in IGF-II
      action on ROB differentiation in vitro.

PMID- 14665442
TI  - Integration of hormone signaling in the regulation of human 25(OH)D3 24
      hydroxylase transcription.
AB  - The current study sought to define the molecular mechanisms involved in the cross
      talk between 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and activators of PKC
      in the regulation of 25(OH)D(3) 24-hydroxlyase [24(OH)ase]. Transfection of the
      h24(OH)ase promoter construct [-5,500/-22 luciferase; vitamin D response elements
      at -294/-274 and -174/-151; AP-1 site at -1,167/-1,160] in vitamin D receptor
      (VDR)-transfected COS-7 cells resulted in strong activation by 1,25(OH)(2)D(3).
      In these cells, cotreatment with the PKC activator TPA and 1,25(OH)(2)D(3)
      yielded a 27-fold increase in luciferase activity, which was 2- to 3-fold greater
      than activation obtained with 1,25(OH)(2)D(3) alone (P < 0.05). Similar results
      were observed using LLCPK-1 kidney cells, suggesting that the previously observed
      enhancement of 1,25(OH)(2)D(3)-induced renal 24(OH)ase mRNA and activity by PKC
      activation occurs at the level of transcription. The functional cooperation
      between PKC activation and VDR was not found to be mediated by the AP-1 site in
      the h24(OH)ase promoter or by enhanced binding of GRIP or DRIP205 to VDR and was
      also not due to PKC-mediated phosphorylation of VDR on Ser(51). Our study
      demonstrates that, in LLCPK-1 kidney cells, the PKC enhancement of
      1,25(OH)(2)D(3)-stimulated transcription may be due, in part, to an increase in
      VDR concentration. In addition, inhibitors of the MAPK pathway were found to
      decrease the TPA enhancement (P < 0.05). Because activation of MAPK has been
      reported to result in the phosphorylation of SRC-1 and in functional cooperation
      between SRC-1 and CREB binding protein, we propose that the potentiation of VDR
      mediated transcription may also be mediated through changes in the
      phosphorylation of specific VDR coregulators.

PMID- 14665443
TI  - Protein calorie restriction has opposite effects on glucose metabolism and
      insulin gene expression in fetal and adult rat endocrine pancreas.
AB  - We previously demonstrated that fetuses from undernourished pregnant rats
      exhibited increased beta-cell mass and hyperinsulinemia, whereas keeping food
      restriction until adult age caused reduced beta-cell mass, hypoinsulinemia, and
      decreased insulin secretion. Because these alterations can be related to insulin
      availability, we have now investigated early and long-term effects of protein
      calorie food restriction on insulin mRNA levels as well as the possible
      mechanisms that could modulate the endogenous insulin mRNA content. We used
      fetuses at 21.5 days of gestation proceeding from food-restricted rats during the
      last week of pregnancy and 70-day-old rats undernourished from day 14 of
      gestation until adult age and with respective controls. Insulin mRNA levels,
      glucose transporters, and total glycolysis and mitochondrial oxidative fluxes
      were evaluated. We additionally analyzed undernutrition effects on signals
      implicated in glucose-mediated insulin gene expression, especially pancreatic
      duodenal homeobox-1 (PDX-1), stress-activated protein kinase-2 (p38/SAPK2), and
      phosphatidylinositol 3-kinase. Undernourished fetuses showed increased insulin
      mRNA, oxidative glucose metabolism, and p38/SAPK2 levels, whereas undernutrition
      until adult age provoked a decrease in insulin gene expression, oxidative glucose
      metabolism, and PDX-1 levels. The results indicate that food restriction caused
      changes in insulin gene expression and content leading to alterations in glucose
      stimulated insulin secretion. The molecular events, increased p38/SAPK2 levels in
      fetuses and decreased PDX-1 levels in adults, seem to be the responsible for the
      altered insulin mRNA expression. Moreover, because PDX-1 activation appears to be
      regulated by glucose-derived metabolite(s), the altered glucose oxidation caused
      by undernutrition could in some manner affect insulin mRNA expression.

PMID- 14665444
TI  - Extremity hyperinsulinemia stimulates muscle protein synthesis in severely
      injured patients.
AB  - Insulin has a well-recognized anabolic effect on muscle protein, yet critically
      ill, severely injured patients are often considered "resistant" to the action of
      insulin. The purpose of this study was to assess the in vivo effects of
      hyperinsulinemia on human skeletal muscle in severely injured patients. To
      accomplish this goal, 14 patients with burns encompassing >40% of their body
      surface area underwent metabolic evaluation utilizing isotopic dilution of
      phenylalanine, femoral artery and vein blood sampling, and sequential muscle
      biopsies of the leg. After baseline metabolic measurements were taken, insulin
      was infused into the femoral artery at 0.45 mIU.min(-1).100 ml leg volume(-1) to
      create a local hyperinsulinemia but with minimal systemic perturbations. Insulin
      administration increased femoral venous concentration of insulin (P < 0.01) but
      with only a 4% (insignificant) decrease in the arterial glucose concentration and
      a 7% (insignificant) decrease in the arterial concentration of phenylalanine.
      Extremity hyperinsulinemia significantly increased leg blood flow (P < 0.05) and
      the rate of muscle protein synthesis (P < 0.05). Neither the rate of muscle
      protein breakdown nor the rate of transmembrane transport of phenylalanine was
      significantly altered with extremity hyperinsulinemia. In conclusion, this study
      demonstrates that insulin directly stimulates muscle protein synthesis in
      severely injured patients.

PMID- 14665445
TI  - Regulation of vasopressin secretion by ETA and ETB receptors in compartmentalized
      rat hypothalamo-neurohypophysial explants.
AB  - The endothelins (ET) have been implicated in vasopressin (AVP) release in vivo
      and in vitro. The effects of ET in this system are complex, and the net AVP
      secretory response likely depends on a unique combination of ET isoform, ET
      receptor subtype, and neural locus. The purpose of these studies was to examine
      the role of ET receptor subtypes at hypothalamic vs. neurohypophysial sites on
      somatodendritic and neurohypophysial AVP secretion. Experiments were done in
      cultured explants of the hypothalamo-neurohypophysial system of Long Evans rats.
      Either the whole explant (standard) or only the hypothalamus or posterior
      pituitary (compartmentalized) was exposed to log dose increases (0.01-10 nM) of
      the agonists ET-1 (ET(A) selective), ET-3 (nonselective), or IRL-1620 (ET(B)
      selective) with or without selective ET(A) (BQ-123, 2-200 nM) or ET(B) (IRL-1038,
      6-600 nM) receptor antagonism. In standard explants, ET-1 and ET-3 dose
      dependently increased, whereas IRL-1620 decreased net AVP release. Hypothalamic
      ET(B) receptor activation increased both somatodendritic and neurohypophysial AVP
      release. At least one intervening synapse was involved, as tetrodotoxin blocked
      the response. Activation of ET(A) receptors at the hypothalamic level inhibited,
      whereas ET(A) receptor activation at the posterior pituitary stimulated,
      neurohypophysial AVP secretion. Antagonism of hypothalamic ET(A) receptors
      potentiated the stimulatory effect of ET-1 and ET-3 on neurohypophysial
      secretion, an effect not observed with ET(B) receptor-induced somatodendritic
      release of AVP. Thus the response of whole explants reflects the net result of
      both stimulatory and inhibitory inputs. The integration of these excitatory and
      inhibitory inputs endows the vasopressinergic system with greater plasticity in
      its response to physiological and pathophysiological states.

PMID- 14665446
TI  - Glucose deprivation enhances targeting of GLUT1 to lipid rafts in 3T3-L1
      adipocytes.
AB  - Glucose deprivation dramatically increases glucose transport activity in 3T3-L1
      adipocytes without changing the concentration of GLUT1 in the plasma membrane
      (PM). Recent data suggest that subcompartments within the PM, specifically lipid
      rafts, may sequester selected proteins and alter their activity. To evaluate this
      possibility, we examined the distribution of GLUT1 in Triton X-100-soluble and 
      insoluble fractions. Our data show that 77% of the GLUT1 pool in PMs isolated
      from control 3T3-L1 adipocytes was extracted by 0.2% Triton X-100. After glucose
      deprivation for 12 h, only 56% of GLUT1 was extracted by detergent. In contrast,
      there was a twofold increase in the GLUT1 content of the detergent-resistant
      fraction. To evaluate whether GLUT1 interacts with a specific protein within
      lipid rafts, we focused on stomatin, recently shown to interact with and inhibit
      GLUT1 activity. Stomatin is distributed about equally between the PM and the
      biosynthetic compartments, and its expression is not affected by glucose
      deprivation. Nearly 90% of the PM pool of stomatin is in detergent-resistant
      lipid rafts. In normal 3T3-L1 adipocytes, we were unable to demonstrate an
      interaction between GLUT1 and stomatin in coimmunoprecipitation experiments.
      However, in stomatin-overexpressing cells, there was clear coprecipitation of
      stomatin with GLUT1 antibodies. Glucose deprivation increased this interaction
      threefold, which may reflect the increase of GLUT1 in lipid rafts. Despite this,
      there was little change in transport activity in glucose-deprived, stomatin
      overexpressing cells vs. that in control cells. Thus GLUT1 interacts with
      stomatin in lipid rafts, but this interaction per se does not alter transport
      activity. Rather, stomatin may serve as an anchor for GLUT1 in lipid rafts, the
      environment of which favors activation.

PMID- 14665447
TI  - Endothelin receptor antagonist reverses decreased NO system in the kidney in vivo
      during exercise.
AB  - Vascular endothelial cells produce endothelin (ET)-1, a potent vasoconstrictor
      peptide, and nitric oxide (NO), a potent vasodilator substance. There are
      interactions between ET-1 and NO. Exercise results in a marked decrease in renal
      blood flow. We previously reported that exercise causes an increase of ET-1
      production in the kidney, whereas production of NO in the kidney is decreased.
      Furthermore, we recently revealed that the magnitude of decrease in blood flow to
      the kidney during exercise was significantly attenuated by the administration of
      the endothelin-A (ET(A)) receptor antagonist, strongly suggesting that
      endogenously increased ET-1 participates in the decrease of blood flow in the
      kidney during exercise. Because it was demonstrated that ET-1 depresses NO
      synthase (NOS) activity of cultured cells in vitro, we hypothesized that an
      increase of ET-1 production in kidney during exercise contributes to a decrease
      of NO production in kidney in vivo. We studied whether administration of the
      ET(A) receptor antagonist attenuates the decreases of NOS activity and NO
      production in the kidney during exercise. Rats performed treadmill running for 30
      min after pretreatment with an ET(A) receptor antagonist (TA-0201, 0.5 mg/kg; TA
      0201-treated exercise group) or vehicle (vehicle-treated exercise group). Control
      rats remained at rest (vehicle-treated sedentary group). Blood flow in the kidney
      was decreased by this exercise, but the magnitude of the decrease after
      pretreatment with TA-0201 was significantly smaller than that after pretreatment
      with vehicle. NOS activity in kidney was significantly lower in the vehicle
      treated exercise group than in the vehicle-treated sedentary group, whereas that
      in the TA-0201-treated exercise group was significantly higher than that in the
      vehicle-treated exercise group. Expressions of endothelial NOS protein and NOx,
      the stable end product of NO, i.e., nitrite/nitrate, concentration in the kidney
      were significantly lower in the vehicle-treated exercise group than in the
      vehicle-treated sedentary group, whereas those in the TA-0201-treated exercise
      group were significantly higher than those in the vehicle-treated exercise group.
      The data suggest that increased ET-1 production in the kidney during exercise
      contributes to the decreases of NOS activity and NO production. Therefore, the
      present study provides a possibility that the exercise-induced increase in
      production of ET-1 in the kidney causes a decrease in blood flow in the kidney
      through two pathways, i.e., vasoconstrictive action and the action of attenuating
      NO production.

PMID- 14665448
TI  - Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women
      with polycystic ovary syndrome.
AB  - Deterioration in glucose tolerance occurs rapidly in women with polycystic ovary
      syndrone (PCOS), suggesting that pancreatic beta-cell dysfunction may supervene
      early. To determine whether the compensatory insulin secretory response to an
      increase in insulin resistance induced by the glucocorticoid dexamethasone
      differs in women with PCOS and control subjects, we studied 10 PCOS and 6 control
      subjects with normal glucose tolerance. An oral glucose tolerance test (OGTT) and
      a graded glucose infusion protocol were performed at baseline and after subjects
      took 2.0 mg of dexamethasone orally. Basal (Phi(b)), static (Phi(s)), dynamic
      (Phi(d)), and global (Phi) indexes of beta-cell sensitivity to glucose were
      derived. Insulin sensitivity (S(i)) was calculated using the minimal model; a
      disposition index (DI) was calculated as the product of S(i) and Phi. PCOS and
      control subjects had nearly identical fasting and 2-h glucose levels at baseline.
      Phi(b) was higher, although not significantly so, in the PCOS subjects. The
      Phi(d), Phi(s), and Phi indexes were 28, 19, and 20% higher, respectively, in
      PCOS subjects. The DI was significantly lower in PCOS (30.01 +/- 5.33 vs. 59.24
      +/- 7.59) at baseline. After dexamethasone, control subjects averaged a 9%
      increase (to 131 +/- 12 mg/dl) in 2-h glucose levels; women with PCOS had a
      significantly greater 26% increase to 155 +/- 6 mg/dl. The C-peptide-to-glucose
      ratios on OGTT increased by 44% in control subjects and by only 15% in PCOS
      subjects. The accelerated deterioration in glucose tolerance in PCOS may result,
      in part, from a relative attenuation in the response of the beta-cell to the
      demand placed on it by factors exacerbating insulin resistance.

PMID- 14665449
TI  - Chlamydomonas reinhardtii at the crossroads of genomics.

PMID- 14665450
TI  - Whole-genome analysis of two-component signal transduction genes in fungal
      pathogens.
AB  - Two-component phosphorelay systems are minimally comprised of a histidine kinase
      (HK) component, which autophosphorylates in response to an environmental
      stimulus, and a response regulator (RR) component, which transmits the signal,
      resulting in an output such as activation of transcription, or of a mitogen
      activated protein kinase cascade. The genomes of the yeasts Saccharomyces
      cerevisiae, Schizosaccharomyces pombe, and Candida albicans encode one, three,
      and three HKs, respectively. In contrast, the genome sequences of the filamentous
      ascomycetes Neurospora crassa, Cochliobolus heterostrophus (Bipolaris maydis),
      Gibberella moniliformis (Fusarium verticillioides), and Botryotinia fuckeliana
      (Botrytis cinerea) encode an extensive family of two-component signaling
      proteins. The putative HKs fall into 11 classes. Most of these classes are
      represented in each filamentous ascomycete species examined. A few of these
      classes are significantly more prevalent in the fungal pathogens than in the
      saprobe N. crassa, suggesting that these groups contain paralogs required for
      virulence. Despite the larger numbers of HKs in filamentous ascomycetes than in
      yeasts, all of the ascomycetes contain virtually the same downstream histidine
      phosphotransfer proteins and RR proteins, suggesting extensive cross talk or
      redundancy among HKs.

PMID- 14665451
TI  - Evidence of sexual recombination among Cryptococcus neoformans serotype A
      isolates in sub-Saharan Africa.
AB  - The most common cause of fungal meningitis in humans, Cryptococcus neoformans
      serotype A, is a basidiomycetous yeast with a bipolar mating system. However, the
      vast majority (>99.9%) of C. neoformans serotype A isolates possess only one of
      the two mating type alleles (MATalpha). Isolates with the other allele (MATa)
      were recently discovered and proven to mate in the laboratory. It has been a
      mystery whether and where C. neoformans strains undergo sexual reproduction.
      Here, we applied population genetic approaches to demonstrate that a population
      of C. neoformans serotype A clinical isolates from Botswana contains an
      unprecedented proportion of fertile MATa isolates and exhibits evidence of both
      clonal expansion and recombination within two partially genetically isolated
      subgroups. Our findings provide evidence for sexual recombination among some
      populations of C. neoformans serotype A from sub-Saharan Africa, which may have a
      direct impact on their evolution.

PMID- 14665452
TI  - SwoHp, a nucleoside diphosphate kinase, is essential in Aspergillus nidulans.
AB  - The temperature-sensitive swoH1 mutant of Aspergillus nidulans was previously
      identified in a screen for mutants with defects in polar growth. In the present
      work, we found that the swoH1 mutant swelled, lysed, and did not produce conidia
      during extended incubation at the restrictive temperature. When shifted from the
      permissive to the restrictive temperature, swoH1 showed the temperature-sensitive
      swelling phenotype only after 8 h at the higher temperature. The swoH gene was
      mapped to chromosome II and cloned by complementation of the temperature
      sensitive phenotype. The sequence showed that swoH encodes a homologue of
      nucleoside diphosphate kinases (NDKs) from other organisms. Deletion experiments
      showed that the swoH gene is essential. A hemagglutinin-SwoHp fusion complemented
      the mutant phenotype, and the purified fusion protein possessed phosphate
      transferase activity in thin-layer chromatography assays. Sequencing of the
      mutant allele showed a predicted V83F change. Structural modeling suggested that
      the swoH1 mutation would lead to perturbation of the NDK active site. Crude cell
      extracts from the swoH1 mutant grown at the permissive temperature had
      approximately 20% of the NDK activity seen in the wild type and did not show any
      decrease in activity when assayed at higher temperatures. Though the data are not
      conclusive, the lack of temperature-sensitive NDK activity in the swoH1 mutant
      raises the intriguing possibility that the SwoH NDK is required for growth at
      elevated temperatures rather than for polarity maintenance.

PMID- 14665453
TI  - The expression of sterigmatocystin and penicillin genes in Aspergillus nidulans
      is controlled by veA, a gene required for sexual development.
AB  - Secondary metabolism is commonly associated with morphological development in
      microorganisms, including fungi. We found that veA, a gene previously shown to
      control the Aspergillus nidulans sexual/asexual developmental ratio in response
      to light, also controls secondary metabolism. Specifically, veA regulates the
      expression of genes implicated in the synthesis of the mycotoxin sterigmatocystin
      and the antibiotic penicillin. veA is necessary for the expression of the
      transcription factor aflR, which activates the gene cluster that leads to the
      production of sterigmatocystin. veA is also necessary for penicillin production.
      Our results indicated that although veA represses the transcription of the
      isopenicillin synthetase gene ipnA, it is necessary for the expression of acvA,
      the key gene in the first step of penicillin biosynthesis, encoding the delta-(L
      alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase. With respect to the mechanism
      of veA in directing morphological development, veA has little effect on the
      expression of the known sexual transcription factors nsdD and steA. However, we
      found that veA regulates the expression of the asexual transcription factor brlA
      by modulating the alpha/beta transcript ratio that controls conidiation.

PMID- 14665454
TI  - Mating and pathogenic development of the Smut fungus Ustilago maydis are
      regulated by one mitogen-activated protein kinase cascade.
AB  - In the phytopathogenic fungus Ustilago maydis, pheromone-mediated cell fusion is
      a prerequisite for the generation of the infectious dikaryon. The pheromone
      signal elevates transcription of the pheromone genes and elicits formation of
      conjugation hyphae. Cyclic AMP and mitogen-activated protein kinase (MAPK)
      signaling are involved in this process. The MAPK cascade is presumed to be
      composed of Ubc4 (MAPK kinase kinase), Fuz7 (MAPK kinase), and Ubc3/Kpp2 (MAPK).
      We isolated the kpp4 gene and found it to be allelic to ubc4. Epistasis analyses
      with constitutively active alleles of kpp4 and fuz7 substantiate that Kpp4, Fuz7,
      and Kpp2/Ubc3 are components of the same module. Moreover, we demonstrate that
      Fuz7 activates Kpp2 and shows interactions in vitro. Signaling via this cascade
      regulates expression of pheromone-responsive genes, presumably through acting on
      the transcription factor Prf1. Interestingly, the same cascade is needed for
      conjugation tube formation, and this process does not involve Prf1. In addition,
      fuz7 as well as kpp4 deletion strains are nonpathogenic, while kpp2 deletion
      mutants are only attenuated in pathogenesis. Here we show that strains expressing
      the unphosphorylatable allele kpp2(T182A/Y184F) are severely affected in tumor
      induction and display defects in early infection-related differentiation.

PMID- 14665456
TI  - Glycosyl phosphatidylinositol-anchored proteins in chemosensory signaling:
      antisense manipulation of Paramecium tetraurelia PIG-A gene expression.
AB  - Glycosyl phosphatidylinositol (GPI)-anchored proteins are peripheral membrane
      proteins tethered to the cell through a lipid anchor. GPI-anchored proteins serve
      many functions in cellular physiology and cell signaling. The PIG-A gene codes
      for one of the enzymes of a complex that catalyzes the first step in anchor
      synthesis, and we have cloned the Paramecium tetraurelia pPIG-A gene using
      homology PCR. To understand the function of pPIG-A and the significance of GPI
      anchored proteins in Paramecium, we reduced the mRNA for pPIG-A in transformed
      cells using an expression vector that transcribed antisense mRNA. The amount of
      transcript is reduced to approximately 0.3% of the mRNA in control-transformed
      cells. Compared to control cells, cells transformed with the antisense pPIG-A
      vector show reduced synthesis of GPI anchor intermediates catalyzed in their
      endoplasmic reticula and a very few GPI-anchored proteins among the peripheral
      proteins that can be recovered from their surfaces. They also show specific
      defects in chemoresponse to glutamate and folate. Other cellular functions, such
      as growth and mating, seem to be normal.

PMID- 14665455
TI  - The yeast protein kinase C cell integrity pathway mediates tolerance to the
      antifungal drug caspofungin through activation of Slt2p mitogen-activated protein
      kinase signaling.
AB  - The echinocandin caspofungin is a new antifungal drug that blocks cell wall
      synthesis through inhibition of beta-(1-3)-glucan synthesis. Saccharomyces
      cerevisiae cells are able to tolerate rather high caspofungin concentrations,
      displaying high viability at low caspofungin doses. To identify yeast genes
      implicated in caspofungin tolerance, we performed a genome-wide microarray
      analysis. Strikingly, caspofungin treatment rapidly induces a set of genes from
      the protein kinase C (PKC) cell integrity signaling pathway, as well as those
      required for cell wall maintenance and architecture. The mitogen-activated
      protein kinase Slt2p is rapidly activated by phosphorylation, triggering
      signaling through the PKC pathway. Cells lacking genes such as SLT2, BCK1, and
      PKC1, as well as the caspofungin target gene, FKS1, display pronounced
      hypersensitivity, demonstrating that the PKC pathway is required for caspofungin
      tolerance. Notably, the cell surface integrity sensor Wsc1p, but not the sensors
      Wsc2-4p and Mid2p, is required for sensing caspofungin perturbations. The
      expression modulation of PKC target genes requires the transcription factor
      Rlm1p, which controls expression of several cell wall synthesis and maintenance
      genes. Thus, caspofungin-induced cell wall damage requires Wsc1p as a dedicated
      sensor to launch a protective response through the activated salvage pathway for
      de novo cell wall synthesis. Our results establish caspofungin as a specific
      activator of Slt2p stress signaling in baker's yeast.

PMID- 14665457
TI  - Molecular identification of a calcium-inhibited catalytic subunit of casein
      kinase type 2 from Paramecium tetraurelia.
AB  - We have previously described the occurrence in Paramecium of a casein kinase (CK)
      activity (EC 2.7.1.37) with some unusual properties, including inhibition by
      Ca(2+) (R. Kissmehl, T. Treptau, K. Hauser, and H. Plattner, FEBS Lett. 402:227
      235, 1995). We now have cloned four genes, PtCK2alpha1 to PtCK2alpha4, all of
      which encode the catalytic alpha subunit of type 2 CK (CK2) with calculated
      molecular masses ranging from 38.9 to 39.4 kDa and pI values ranging from 8.8 to
      9.0. They can be classified into two groups, which differ from each other by 28%
      on the nucleotide level and by 18% on the derived amino acid level. One of them,
      PtCK2alpha3, has been expressed in Escherichia coli and characterized in vitro.
      As we also have observed with the isolated CK, the recombinant protein
      preferentially phosphorylates casein but also phosphorylates some Paramecium
      specific substrates, including the exocytosis-sensitive phosphoprotein
      pp63/parafusin. Characteristically, Ca(2+) inhibits the phosphorylation at
      elevated concentrations occurring during stimulation of a cell. Reconstitution
      with a recombinant form of the regulatory subunit from Xenopus laevis, XlCK2beta,
      confirms Ca(2+) sensitivity also under conditions of autophosphorylation. This is
      unusual for CK2 but correlates with the presence of two EF-hand calcium-binding
      motifs, one of which is located in the N-terminal segment essential for
      constitutive activity, as well as with an aberrant composition of normally basic
      domains recognizing acidic substrate domains. Immunogold localization reveals a
      considerable enrichment in the outermost cell cortex layers, excluding cilia. We
      discuss a potential role of this Ca(2+)-inhibited PtCK2alpha species in a late
      step of signal transduction.

PMID- 14665459
TI  - pH response transcription factor PacC controls salt stress tolerance and
      expression of the P-Type Na+ -ATPase Ena1 in Fusarium oxysporum.
AB  - Fungi possess efficient mechanisms of pH and ion homeostasis, allowing them to
      grow over a wide range of environmental conditions. In this study, we addressed
      the role of the pH response transcription factor PacC in salt tolerance of the
      vascular wilt pathogen Fusarium oxysporum. Loss-of-function pacC(+/-) mutants
      showed increased sensitivity to Li(+) and Na(+) and accumulated higher levels of
      these cations than the wild type. In contrast, strains expressing a dominant
      activating pacC(c) allele were more salt tolerant and had lower intracellular
      Li(+) and Na(+) concentrations. Although the kinetics of Li(+) influx were not
      altered by mutations in pacC, we found that Li(+) efflux at an alkaline, but not
      at an acidic, ambient pH was significantly reduced in pacC(+/-) loss-of-function
      mutants. To explore the presence of a PacC-dependent efflux mechanism in F.
      oxysporum, we cloned ena1 encoding an orthologue of the yeast P-type Na(+)-ATPase
      ENA1. Northern analysis revealed that efficient transcriptional activation of
      ena1 in F. oxysporum required the presence of high Na(+) concentrations and
      alkaline ambient pH and was dependent on PacC function. We propose a model in
      which PacC controls ion homeostasis in F. oxysporum at a high pH by activating
      expression of ena1 coordinately with a second Na(+)-responsive signaling pathway.

PMID- 14665458
TI  - Cysteine proteases and cell differentiation: excystment of the ciliated protist
      Sterkiella histriomuscorum.
AB  - The process of excystment of Sterkiella histriomuscorum (Ciliophora,
      Oxytrichidae) leads in a few hours, through a massive influx of water and the
      resorption of the cyst wall, from an undifferentiated resting cyst to a highly
      differentiated and dividing vegetative cell. While studying the nature of the
      genes involved in this process, we isolated three different cysteine proteases
      genes, namely, a cathepsin B gene, a cathepsin L-like gene, and a calpain-like
      gene. Excystation was selectively inhibited at a precise differentiating stage by
      cysteine proteases inhibitors, suggesting that these proteins are specifically
      required during the excystment process. Reverse transcription-PCR experiments
      showed that both genes display differential expression between the cyst and the
      vegetative cells. A phylogenetic analysis showed for the first time that the
      cathepsin B tree is paraphyletic and that the diverging S. histriomuscorum
      cathepsin B is closely related to its Giardia homologues, which take part in the
      cyst wall breakdown process. The deduced cathepsin L-like protein sequence
      displays the structural signatures and phylogenetic relationships of cathepsin H,
      a protein that is known only in plants and animals and that is involved in the
      degradation of extracellular matrix components in cancer diseases. The deduced
      calpain-like protein sequence does not display the calcium-binding domain of
      conventional calpains; it belongs to a diverging phylogenetic cluster that
      includes Aspergillus palB, a protein which is involved in a signal transduction
      pathway that is sensitive to ambient pH.

PMID- 14665460
TI  - Use of cDNA microarrays to monitor transcriptional responses of the chestnut
      blight fungus Cryphonectria parasitica to infection by virulence-attenuating
      hypoviruses.
AB  - Hypoviruses are a family of cytoplasmically replicating RNA viruses of the
      chestnut blight fungus Cryphonectria parasitica. Members of this mycovirus family
      persistently alter virulence (hypovirulence) and related fungal developmental
      processes, including asexual and sexual sporulation. In order to gain a better
      understanding of the molecular basis for these changes, we have developed a C.
      parasitica cDNA microarray to monitor global transcriptional responses to
      hypovirus infection. In this report, a spotted DNA microarray representing
      approximately 2,200 C. parasitica genes was used to monitor changes in the
      transcriptional profile after infection by the prototypic hypovirus CHV1-EP713.
      Altered transcript abundance was identified for 295 clones (13.4% of the 2,200
      unique cDNAs) as a result of CHV1-EP713 infection-132 up-regulated and 163 down
      regulated. In comparison, less than 20 specific C. parasitica genes were
      previously identified by Northern analysis and mRNA differential display as being
      responsive to hypovirus infection. A 93% validation rate was achieved between
      real-time reverse transcription-PCR results and microarray predictions.
      Differentially expressed genes represented a broad spectrum of biological
      functions, including stress responses, carbon metabolism, and transcriptional
      regulation. These findings are consistent with the view that infection by a 12.7
      kbp hypovirus RNA results in a persistent reprogramming of a significant portion
      of the C. parasitica transcriptome. The potential impact of microarray studies on
      current and future efforts to establish links between hypovirus-mediated changes
      in cellular gene expression and phenotypes is discussed.

PMID- 14665461
TI  - EAP1, a Candida albicans gene involved in binding human epithelial cells.
AB  - Candida albicans adhesion to host tissues contributes to its virulence and
      adhesion to medical devices permits biofilm formation, but we know relatively
      little about the molecular mechanisms governing C. albicans adhesion to materials
      or mammalian cells. Saccharomyces cerevisiae provides an attractive model system
      for studying adhesion in yeast because of its well-characterized genetics and
      gene expression systems and the conservation of signal transduction pathways
      among the yeasts. In this study, we used a parallel plate flow chamber to screen
      and characterize attachment of a flo8Delta S. cerevisiae strain expressing a C.
      albicans genomic library to a polystyrene surface. The gene EAP1 was isolated as
      a putative cell wall adhesin. Sequence analysis of EAP1 shows that it contains a
      signal peptide, a glycosylphosphatidylinositol anchor site, and possesses
      homology to many other yeast genes encoding cell wall proteins. In addition to
      increasing adhesion to polystyrene, heterologous expression of EAP1 in S.
      cerevisiae and autonomous expression of EAP1 in a C. albicans efg1 homozygous
      null mutant significantly enhanced attachment to HEK293 kidney epithelial cells.
      EAP1 expression also restored invasive growth to haploid flo8Delta and flo11Delta
      strains as well as filamentous growth to diploid flo8/flo8 and flo11/flo11
      strains. Transcription of EAP1 in C. albicans is regulated by the transcription
      factor Efg1p, suggesting that EAP1 expression is activated by the cyclic AMP
      dependent protein kinase pathway.

PMID- 14665462
TI  - Sla1, a Schizosaccharomyces pombe homolog of the human La protein, induces
      ectopic meiosis when its C terminus is truncated.
AB  - Sla1 is a Schizosaccharomyces pombe homolog of the human La protein. La proteins
      are known to be RNA-binding proteins that bear conserved RNA recognition motifs
      (La and RRMs), but their biological functions still have not been fully resolved.
      In this study, we show that the S. pombe La homolog (Sla1) is involved in
      regulating sexual development. Sla1 truncated in the C terminus (Sla1DeltaC)
      induced ectopic sporulation in the ras1Delta strain and several other sporulation
      deficient mutants. The C terminus contains a nuclear localization signal. While
      full-length Sla1 localizes in the nucleus, Sla1DeltaC is found throughout the
      cell, suggesting the cytoplasmic localization of Sla1DeltaC is involved in its
      sporulation-inducing activity. Further deletion analysis of Sla1 indicated that a
      small region (35 amino acids) that includes a portion of RRM2 is sufficient to
      induce sporulation. The La motif (RRM1) is not involved in this activity.
      Strikingly, Sla1DeltaC induced haploid meiosis in a heterothallic strain, similar
      to the pat1-114 or mei2-SATA mutation. Sla1DeltaC induced sporulation in a mei3
      disruptant but not in a mei2 disruptant, indicating that Sla1DeltaC requires Mei2
      to induce haploid meiosis. Deletion of the chromosomal sla1 gene lowered the
      temperature sensitivity of the pat1-114 mutant. Two-hybrid analysis indicated
      that Pat1 interacts with Sla1DeltaC but not full-length Sla1. Thus, Sla1DeltaC
      may block Pat1 activity. This block would remove the inhibition on Mei2, which
      would then drive the cell into haploid meiosis. Finally, Sla1 was degraded prior
      to the start of meiosis when we monitored Sla1 in cells in which meiosis was
      synchronously induced. The ability of truncated Sla1 to induce ectopic meiosis
      represents a very novel function that has hitherto not been suspected for the La
      family of proteins.

PMID- 14665463
TI  - Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent
      exclusion of TATA binding protein.
AB  - The Tup1-Ssn6 general repression complex in Saccharomyces cerevisiae represses a
      wide variety of regulons. Regulon-specific DNA binding proteins recruit the
      repression complex, and their synthesis, activity, or localization controls the
      conditions for repression. Rox1 is the hypoxic regulon-specific protein, and a
      second DNA binding protein, Mot3, augments repression at tightly controlled
      genes. We addressed the requirements for Tup1-Ssn6 recruitment to two hypoxic
      genes, ANB1 and HEM13, by using chromatin immunoprecipitation assays. Either Rox1
      or Mot3 could recruit Ssn6, but Tup1 recruitment required Ssn6 and Rox1. We also
      monitored events during derepression. Rox1 and Mot3 dissociated from DNA quickly,
      accounting for the rapid accumulation of ANB1 and HEM13 RNAs, suggesting a simple
      explanation for induction. However, Tup1 remained associated with these genes,
      suggesting that the localization of Tup1-Ssn6 is not the sole determinant of
      repression. We could not reproduce the observation that deletion of the Tup1-Ssn6
      interacting protein Cti6 was required for induction. Finally, Tup1 is capable of
      repression through a chromatin-dependent mechanism, the positioning of a
      nucleosome over the TATA box, or a chromatin-independent mechanism. We found that
      the rate of derepression was independent of the positioned nucleosome and that
      the TATA binding protein was excluded from ANB1 even in the absence of the
      positioned nucleosome. The mediator factor Srb7 has been shown to interact with
      Tup1 and to play a role in repression at several regulons, but we found that
      significant levels of repression remained in srb7 mutants even when the chromatin
      dependent repression mechanism was eliminated. These findings suggest that the
      repression of different regulons or genes may invoke different mechanisms.

PMID- 14665464
TI  - Saccharomyces cerevisiae histidine phosphotransferase Ypd1p shuttles between the
      nucleus and cytoplasm for SLN1-dependent phosphorylation of Ssk1p and Skn7p.
AB  - Sln1p is a plasma membrane-localized two-component histidine kinase that
      functions as an osmotic stress sensor in Saccharomyces cerevisiae. Changes in
      osmotic pressure modulate Sln1p kinase activity, which, together with Ypd1p, a
      phosphorelay intermediate, changes the phosphorylation status of two response
      regulators, Ssk1p and Skn7p. Ssk1p controls the activity of the HOG1 mitogen
      activated protein kinase pathway. Skn7p is a nuclearly localized transcription
      factor that regulates genes involved in cell wall integrity and other processes.
      Subcellular compartmentalization may therefore play an important role in
      eukaryotic two-component pathway regulation. We have studied the subcellular
      localization of SLN1 pathway components and find that Ypd1p is a dynamic protein
      with a role in shuttling the osmotic stress signal from Sln1p to Ssk1p in the
      cytosol and to Skn7p in the nucleus. The need to translocate the signal into
      different intracellular compartments contributes a spatial dimension to
      eukaryotic two-component pathways compared to the prototypical two-component
      pathways of prokaryotes.

PMID- 14665465
TI  - Two Dictyostelium orthologs of the prokaryotic cell division protein FtsZ
      localize to mitochondria and are required for the maintenance of normal
      mitochondrial morphology.
AB  - In bacteria, the protein FtsZ is the principal component of a ring that
      constricts the cell at division. Though all mitochondria probably arose through a
      single, ancient bacterial endosymbiosis, the mitochondria of only certain
      protists appear to have retained FtsZ, and the protein is absent from the
      mitochondria of fungi, animals, and higher plants. We have investigated the role
      that FtsZ plays in mitochondrial division in the genetically tractable protist
      Dictyostelium discoideum, which has two nuclearly encoded FtsZs, FszA and FszB,
      that are targeted to the inside of mitochondria. In most wild-type amoebae, the
      mitochondria are spherical or rod-shaped, but in fsz-null mutants they become
      elongated into tubules, indicating that a decrease in mitochondrial division has
      occurred. In support of this role in organelle division, antibodies to FszA and
      FszA-green fluorescent protein (GFP) show belts and puncta at multiple places
      along the mitochondria, which may define future or recent sites of division. FszB
      GFP, in contrast, locates to an electron-dense, submitochondrial body usually
      located at one end of the organelle, but how it functions during division is
      unclear. This is the first demonstration of two differentially localized FtsZs
      within the one organelle, and it points to a divergence in the roles of these two
      proteins.

PMID- 14665466
TI  - Dictyostelium discoideum developmentally regulated genes whose expression is
      dependent on MADS box transcription factor SrfA.
AB  - The MADS box transcription factor SrfA is required for spore differentiation in
      Dictyostelium discoideum. srfA null strains form rounded spores that do not
      resist adverse environmental conditions. Five genes whose expression is dependent
      on SrfA have been isolated by differential hybridization. One of these genes,
      sigC, is identical to phg1b, previously characterized in mutants with altered
      adhesive properties and found to encode a nine-transmembrane-domain protein. This
      gene is transcribed into two mRNAs as the result of alternative splicing of two
      internal exons. The slower-migrating mRNA codes for a shorter protein that lacks
      the first transmembrane fragment and is not expressed in srfA null strains. The
      other four genes (sigA, sigB, sigD, and 45D) are expressed only during late
      developmental stages. In situ hybridization experiments showed that expression of
      sigA, sigB, and sigD is restricted to the sorus of developing structures. sigA
      codes for a homologue of malate dehydrogenase that converts pyruvate to malate to
      replenish the tricarboxylic acid cycle. sigB encodes a protein with significant
      similarity to the GP63 metalloproteinase of Leishmania, leishmanolysin. The
      sequence of SigD is highly similar to that of several spore coat proteins of D.
      discoideum, and it may play a role in that structure. The gene 45D codes for an
      RNA-binding protein homologue whose expression is also dependent on the GATA
      transcription factor stalky (StkA). The expression of sigB is also dependent on
      both SrfA and StkA. The expression of 45D, but not of sigA, sigB, sigC, and sigD,
      can be induced in srfA null cells by constitutive protein kinase A activation.
      Strains in which either sigA, sigB, or sigD is disrupted were isolated and found
      to form spores that are not detectably different from those of wild-type strains.

PMID- 14665468
TI  - MFalpha1, the gene encoding the alpha mating pheromone of Candida albicans.
AB  - Candida albicans, the single most frequently isolated human fungal pathogen, was
      thought to be asexual until the recent discovery of the mating-type-like locus
      (MTL). Homozygous MTL strains were constructed and shown to mate. Furthermore, it
      has been demonstrated that opaque-phase cells are more efficient in mating than
      white-phase cells. The similarity of the genes involved in the mating pathway in
      Saccharomyces cerevisiae and C. albicans includes at least one gene (KEX2) that
      is involved in the processing of the alpha mating pheromone in the two yeasts.
      Taking into account this similarity, we searched the C. albicans genome for
      sequences that would encode the alpha pheromone gene. Here we report the
      isolation and characterization of the gene MFalpha1, which codes for the
      precursor of the alpha mating pheromone in C. albicans. Two active alpha
      peptides, 13 and 14 amino acids long, would be generated after the precursor
      molecule is processed in C. albicans. To examine the role of this gene in mating,
      we constructed an mfalpha1 null mutant of C. albicans. The mfalpha1 null mutant
      fails to mate as MTLalpha, while MTLa mfalpha1 cells are still mating competent.
      Experiments performed with the synthetic alpha-peptides show that they are
      capable of inducing growth arrest, as demonstrated by halo tests, and also induce
      shmooing in MTLa cells of C. albicans. These peptides are also able to complement
      the mating defect of an MTLalpha kex2 mutant strain when added exogenously,
      thereby confirming their roles as alpha mating pheromones.

PMID- 14665467
TI  - Cryptococcus neoformans gene expression during experimental cryptococcal
      meningitis.
AB  - Cryptococcus neoformans, an encapsulated basidiomycete fungus of medical
      importance, is capable of crossing the blood-brain barrier and causing meningitis
      in both immunocompetent and immunocompromised individuals. To gain insight into
      the adaptation of the fungus to the host central nervous system (CNS), serial
      analysis of gene expression (SAGE) was used to characterize the gene expression
      profile of C. neoformans cells recovered from the CNS of infected rabbits. A SAGE
      library was constructed, and 49,048 tags were sequenced; 16,207 of these tags
      were found to represent unique sequences or tag families. Of the 304 most
      abundant tags, 164 were assigned to a putative gene for subsequent functional
      grouping. The results (as determined according to the number of tags that
      identified genes encoding proteins required for these functions) indicated that
      the C. neoformans cells were actively engaged in protein synthesis, protein
      degradation, stress response, small-molecule transport, and signaling. In
      addition, a high level of energy requirement of the fungal cells was suggested by
      a large number of tags that matched putative genes for energy production. Taken
      together, these findings provide the first insight into the transcriptional
      adaptation of C. neoformans to the host environment and identify the set of
      fungal genes most highly expressed during cerebrospinal fluid infection.

PMID- 14665469
TI  - Functional characterization of Candida albicans ABC transporter Cdr1p.
AB  - In view of the importance of Candida drug resistance protein (Cdr1p) in azole
      resistance, we have characterized it by overexpressing it as a green fluorescent
      protein (GFP)-tagged fusion protein (Cdr1p-GFP). The overexpressed Cdr1p-GFP in
      Saccharomyces cerevisiae is shown to be specifically labeled with the
      photoaffinity analogs iodoarylazidoprazosin (IAAP) and azidopine, which have been
      used to characterize the drug-binding sites on mammalian drug-transporting P
      glycoproteins. While nystatin could compete for the binding of IAAP, miconazole
      specifically competed for azidopine binding, suggesting that IAAP and azidopine
      bind to separate sites on Cdr1p. Cdr1p was subjected to site-directed mutational
      analysis. Among many mutant variants of Cdr1p, the phenotypes of F774A and
      DeltaF774 were particularly interesting. The analysis of GFP-tagged mutant
      variants of Cdr1p revealed that a conserved F774, in predicted transmembrane
      segment 6, when changed to alanine showed increased binding of both photoaffinity
      analogues, while its deletion (DeltaF774), as revealed by confocal microscopic
      analyses, led to mislocalization of the protein. The mislocalized DeltaF774
      mutant Cdr1p could be rescued to the plasma membrane as a functional transporter
      by growth in the presence of a Cdr1p substrate, cycloheximide. Our data for the
      first time show that the drug substrate-binding sites of Cdr1p exhibit striking
      similarities with those of mammalian drug-transporting P-glycoproteins and
      despite differences in topological organization, the transmembrane segment 6 in
      Cdr1p is also a major contributor to drug substrate-binding site(s).

PMID- 14665470
TI  - Sporangium-specific gene expression in the oomycete phytopathogen Phytophthora
      infestans.
AB  - The oomycete genus Phytophthora includes many of the world's most destructive
      plant pathogens, which are generally disseminated by asexual sporangia. To
      identify factors relevant to the biology of these propagules, genes induced in
      sporangia of the potato late blight pathogen Phytophthora infestans were isolated
      using cDNA macroarrays. Of approximately 1,900 genes known to be expressed in
      sporangia, 61 were up-regulated >5-fold in sporangia versus hyphae based on the
      arrays, including 17 that were induced >100-fold. A subset were also activated by
      starvation and in a nonsporulating mutant. mRNAs of some genes declined in
      abundance after germination, while others persisted through the germinated
      zoospore cyst stage. Functions were predicted for about three-quarters of the
      genes, including potential regulators (protein kinases and phosphatases,
      transcription factors, and G-protein subunits), transporters, and metabolic
      enzymes. Predominant among the last were several dehydrogenases, especially a
      highly expressed sorbitol dehydrogenase that accounted for 3% of the mRNA.
      Sorbitol dehydrogenase activity also rose during sporulation and several stress
      treatments, paralleling the expression of the gene. Another interesting metabolic
      enzyme resembled creatine kinases, which previously were reported only in animals
      and trypanosomes. These results provide insight into the transcriptional and
      cellular processes occurring in sporangia and identify potential targets for crop
      protection strategies.

PMID- 14665472
TI  - Low voltage with pericardial effusion: complexity of mechanisms.

PMID- 14665471
TI  - Recognizing the link between peripheral edema and voltage attenuation of QRS
      complexes: implications for the critical care patient.

PMID- 14665473
TI  - Drug therapy for pulmonary arterial hypertension: what's on the menu today?

PMID- 14665474
TI  - Pulmonary cryptococcosis in normal hosts: treat or observe?

PMID- 14665475
TI  - What is the prognosis for using the pneumonia severity index to make site-of-care
      decisions in community-acquired pneumonia?

PMID- 14665476
TI  - The seduction of asthma severity categorization.

PMID- 14665478
TI  - A comparison of 2-lead, 6-lead, and 12-lead ECGs in patients with changing
      edematous states: implications for the employment of quantitative
      electrocardiography in research and clinical applications.
AB  - OBJECTIVE: Precordial ECGs reveal significant intrasubject variability due to the
      inexact employment of the recommended V(1)-V(6) chest landmarks. Also, as per the
      Einthoven law, the six limb leads can be derived from leads 1 and 2. The purpose
      of this study was to evaluate whether the 12-lead ECG could be substituted by ECG
      sets with a limited number of leads. MATERIALS AND METHODS: The performance of
      three ECG systems (ie, the 12-lead ECG, a 6-lead ECG comprising the limb leads,
      and a 2-lead ECG comprising exclusively leads 1 and 2) was evaluated in data from
      28 patients with anasarca (AN), 28 control patients, 10 patients who had
      undergone hemodialysis, and 3 patients with idiopathic dilated cardiomyopathy.
      RESULTS: Linear regression analyses of changes in ECG data with the weight gain
      of patients with AN and the intercorrelations of the three ECG systems in the
      various patient subgroups were found to be statistically significant at p =
      0.0005 and r values ranging from 0.61 to 0.99, which are suggestive of
      good/excellent correlations. However, regression analyses of peak weight (PW)
      gain with changes in the 2-lead ECG (r = 0.43; p = 0.02) and 6-lead ECG (r =
      0.48; p = 0.01), and half of PW gain and 12-lead ECG (r = 0.41; p = 0.03), 6-lead
      ECG (r= 0.18; p = 0.35), and 2-lead ECG (r = 0.43; p = 0.02) revealed poor
      correlations. CONCLUSION: ECG systems, comprising 2 or 6 leads, can be
      substituted for the 12-lead ECG for certain clinical and research applications
      (pertaining to the amplitude of QRS complexes), attesting to the inherent
      redundancy of the information from the 12-lead ECG.

PMID- 14665480
TI  - Clinical significance of low voltage in asymptomatic patients with pericardial
      effusion free of heart disease.
AB  - STUDY OBJECTIVE: The purpose of this study was to evaluate the diagnostic value
      of low voltage with PR-segment and ST-T wave changes in determining the amount of
      clinically silent pericardial effusion detected in a routine echocardiography.
      DESIGN: Consecutive case series analysis. SETTING: Noninvasive cardiology
      department of a university hospital. PATIENTS: Among 8,041 consecutive patients
      referred to our echocardiography laboratory, 121 asymptomatic patients with
      pericardial effusion free of heart disease were studied. INTERVENTIONS:
      Echocardiography and ECG. MEASUREMENTS AND RESULTS: The amount (small or
      moderate/large) of pericardial effusion was correlated with ECG. Among 121
      patients with pericardial effusion, low voltage was detected in 32 patients
      (26%), while widespread PR-segment depression was observed in 32 patients (26%)
      and widespread ST-segment elevation in 8 patients (7%). Although there was a
      significantly higher incidence of low voltage in patients with moderate/large
      pericardial effusion compared to that of small pericardial effusion, 13 of 32
      patients (41%) with low voltage had a small pericardial effusion. In patients
      with a small pericardial effusion, 7 of 13 patients (54%) with low voltage had PR
      segment depression, while 15 of 85 patients (18%) without low voltage had PR
      segment depression; the difference was significant (p = 0.011). In patients with
      moderate/large pericardial effusions, there was no significant difference in the
      incidence of PR-segment depression between patients with and without low voltage
      (47% vs 25%, respectively; p = 0.791). CONCLUSIONS: In the presence of PR-segment
      depression, even a small pericardial effusion may cause low voltage in the
      surface ECG.

PMID- 14665481
TI  - Lipomatous hypertrophy of the interatrial septum: a prospective study of
      incidence, imaging findings, and clinical symptoms.
AB  - BACKGROUND: Lipomatous hypertrophy of the interatrial septum (LHIS) is a benign
      disorder characterized by fat accumulation in the interatrial septum. It
      typically occurs in elderly, obese patients and may cause arrhythmia. OBJECTIVES:
      The purpose of this study was to determine the imaging features of this cardiac
      pathology using multislice CT (MSCT), and its relationship with clinical
      findings. MATERIALS AND METHODS: A total of 1,292 consecutive patients who
      underwent MSCT of the thorax from September 2001 to August 2002 were
      prospectively studied. Beside the analysis of patient records, the amount of fat
      in the interatrial septum, and its size and shape were determined. RESULTS: Among
      the 1,292 patients investigated, we found 28 (2.2%) with LHIS. The mean age of
      affected patients was 72.2 years. MSCT studies revealed a mass of fat attenuation
      with sharp margins and sparing of the fossa ovalis, resulting in a dumbbell shape
      in all patients. The median thickness of the interatrial septum was 32 mm (range,
      20 to 62 mm), and the median craniocaudal extend was 62 mm (range, 51 to 89 mm).
      Twenty-one patients (75.0%) showed increased epicardial fat, 18 patients (64.3%)
      had significant pulmonary emphysema, and 13 of 21 patients (61.9%) showed ECG
      abnormalities. Three patients underwent functional cardiac MRI studies. In one
      patient, hemodynamic obstruction by LHIS was shown. CONCLUSIONS: MSCT scanning is
      a useful method to diagnose LHIS, a cardiac condition that in our series reached
      a 2.2% incidence. The lesion shows characteristic features, thus differentiating
      it from other cardiac tumors. Advanced age, obesity, pulmonary emphysema, and
      atrial arrhythmias are common additional findings in patients with LHIS.

PMID- 14665482
TI  - Did the widespread use of long-acting calcium antagonists decrease the occurrence
      of variant angina?
AB  - BACKGROUND: We have not often encountered variant angina (VA) since the use of
      long-acting calcium antagonists (L-CAs) became widespread. OBJECTIVES: This study
      examined the frequency of VA retrospectively. METHODS: and results: We diagnosed
      angiographically confirmed coronary spastic angina (CSA) in 349 consecutive
      patients using selective spasm provocation tests from January 1991 to December
      2002. During this period, 3,148 diagnostic cardiac catheterizations and 1,515
      selective spasm provocation tests were performed. Seventy-four of these 349
      patients (21.2%) had VA. Coronary spasms were defined as transient luminal
      narrowings of > 99%, and VA was defined as an ST elevation during spontaneous
      attacks or noninvasive stress tests. We classified the 12 years of the study into
      four periods of 3 years each. No tendency to decrease for the ratio of the number
      of patients with CSA and the number of selective spasm provocation tests was
      observed among the four time periods (18%, 24%, 32%, and 23%, respectively).
      However, the number of patients with VA (28, 33, 9, and 4) and the VA/CSA ratio
      (32%, 28%, 14%, and 5%, respectively) in the four group significantly decreased.
      The frequency of administration of calcium antagonists (CAs) before hospital
      admission (49% vs 33%, respectively; p < 0.05) was significantly higher in the
      last time period (from 2000 to 2002) than in the first period (from 1991 to
      1993). L-CAs were administered in > 90% of CSA patients who had been medicated
      with CAs before hospital admission in the last period (from 2000 to 2002), while
      L-CAs were administered in only 20% in the former period (from 1991 to 1993). The
      administration of statins and angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers before hospital admission gradually
      increased according to the period passed, but not significantly. CONCLUSION: The
      frequency of VA has decreased in Japan, possibly due to the widespread use of
      therapy with L-CAs.

PMID- 14665483
TI  - Sex differences in use of coronary revascularization in elderly patients after
      acute myocardial infarction: a tale of two therapies.
AB  - OBJECTIVES: To determine if there are sex differences in the use of coronary
      revascularization in elderly patients after acute myocardial infarction (AMI),
      and if sex differences vary by type of revascularization therapy. DESIGN:
      Retrospective analysis of medical record data. SETTING: US acute-care
      nongovernment hospitals. PATIENTS: A total of 66,830 Medicare patients > or =65
      years old hospitalized with AMI. INTERVENTIONS: None. MEASUREMENTS AND RESULTS:
      We assessed sex differences in the use of coronary revascularization within 60
      days of hospital admission among patients who had undergone cardiac
      catheterization. Multivariable logistic regression models were used to derive
      risk-standardized rates of any coronary revascularization, coronary artery bypass
      graft (CABG) surgery, and percutaneous coronary intervention (PCI) adjusted for
      patient and hospital characteristics. Women had lower crude overall rates of
      coronary revascularization compared with men (65.2% vs 68.7%, p < 0.001).
      Multivariable adjustment reduced the sex difference in the overall coronary
      revascularization rate from 3.5 to 2.1% (66.0% women vs 68.1% men, p = 0.001).
      Sex differences in coronary revascularization use, however, varied by type of
      revascularization therapy. Women had lower risk-standardized rates of CABG
      surgery compared with men (27.0% vs 32.9%, p < 0.001), but had higher risk
      standardized rates of PCI (42.0% vs 38.2%, p < 0.001), particularly among
      patients > 85 years old (45.8% vs 38.9%, p = 0.011). CONCLUSIONS: Among Medicare
      patients hospitalized with AMI, women are slightly less likely to undergo
      coronary revascularization after cardiac catheterization; however, sex
      differences in coronary revascularization vary by type of therapy.

PMID- 14665484
TI  - Treatment of pulmonary arterial hypertension: a preliminary decision analysis.
AB  - STUDY OBJECTIVE: New therapies for pulmonary arterial hypertension (PAH) improve
      functional status, quality of life (QOL), and survival. Clinicians must chose
      between very different therapies without the availability of comparison studies.
      We constructed a "virtual" clinical trial to help inform these treatment choices.
      DESIGN: We compare key outcomes related to survival, costs, and QOL using a
      Markov-type decision model to estimate the expected outcomes and costs for PAH
      patients treated for 1 year with bosentan and treprostinil compared to patients
      treated with epoprostenol, as well as patients treated with bosentan compared to
      those treated with treprostinil. The allowed transitions in the model were
      between World Health Organization functional class I to IV and death. Transition
      probabilities were based on observed transitions for bosentan. Treatment effect
      was estimated using 6-min walk data for treprostinil and epoprostenol. Utilities
      were calculated from estimated EuroQol health states. Cost was estimated from
      average wholesale price and Medicare reimbursement data. The effects of changing
      values of input variables on the key outcomes were calculated. RESULTS: Treatment
      with bosentan compared to treatment with either epoprostenol or treprostinil was
      less costly and resulted in a greater gain in quality-adjusted life years
      (QALYs). Conversely, treprostinil was significantly more expensive than
      epoprostenol, without an appreciable gain in QALYs. These findings were not
      substantially affected by the reasonable adjustments of transition probabilities,
      utility values, or tachyphylaxis to epoprostenol. CONCLUSION: Treatment with
      bosentan is more cost-effective than treatment with either treprostinil or
      epoprostenol. In addition, a net improvement in quality-adjusted survival may be
      expected.

PMID- 14665485
TI  - Pulmonary hypertension in patients with chronic renal failure: role of
      parathyroid hormone and pulmonary artery calcifications.
AB  - RATIONALE: The aim of this work was to study the association of pulmonary
      hypertension (PH) with pulmonary artery calcifications (PACs) and
      hyperparathyroidism in patients with chronic renal failure (CRF) receiving
      regular hemodialysis. BACKGROUND: Scarce data are available regarding the
      prevalence and the predictors of PH in patients with CRF. Abnormal (99m)Tc
      diphosphonate lung uptake was reported in these patients, suggesting a role of
      PACs. METHODS: We studied 51 patients (28 men and 23 women) with end-stage renal
      disease, who were receiving regular hemodialysis. Patients underwent two
      dimensional, Doppler echocardiographic imaging. Laboratory investigations
      included BUN, serum creatinine, calcium, phosphorus, alkaline phosphatase, and
      intact molecule parathormone. PH was defined as pulmonary artery systolic
      pressure > 35 mm Hg as determined by Doppler echocardiographic evaluation.
      RESULTS: PH was detected in 15 patients (29%). Women had a higher prevalence of
      PH (48% vs 14%, p = 0.01). There was no significant differences between patients
      with PH and those without PH with regards to age, duration of dialysis, serum
      calcium (9.6 +/- 2 mg/dL vs 10 +/- 2 mg/dL), phosphorus (6 +/- 1.4 mg/L vs 6.2 +/
      1.9 mg/L), alkaline phosphatase (609 +/- 768 U/L vs 473 +/- 574 U/L),
      parathyroid hormone (PTH) [420 +/- 512 pg/mL vs 354 +/- 519 pg/mL] or the
      prevalence of an abnormal (99m)Tc diphosphate lung scan result (60% vs 73%,
      respectively [+/- SD]). CONCLUSIONS: This study demonstrated that 29% of patients
      with CRF receiving regular hemodialysis have PH. The presence of PH was not
      related to the level of PTH or the severity of other metabolic abnormalities.
      There was no relation between PH and the presence or the severity of PAC. PH is
      detected more frequently in women. This study does not support a role of
      secondary hyperparathyroidism and subsequent PAC as the etiology of PH in
      patients with CRF.

PMID- 14665486
TI  - Age and risk of pulmonary arterial hypertension in scleroderma.
AB  - STUDY OBJECTIVES: To investigate whether age at disease onset is a risk factor
      for pulmonary arterial hypertension (PAH) in scleroderma. SETTING: Scleroderma
      center. PATIENTS: Seven hundred nine consecutive scleroderma patients who
      underwent echocardiography. MEASUREMENTS: The risk of PAH associated with age at
      disease onset was modeled as both a continuous and categorical variable. Risk
      estimates were adjusted for sex, race, scleroderma subtype, disease duration,
      smoking status, FVC, anticentromere and antitopoisomerase I antibody status.
      RESULTS: Overall, 274 patients (38.6%), 272 patients by Doppler echocardiography
      and 2 patients by M-mode echocardiography, had PAH at baseline or during follow
      up. There were 114 patients with mild PAH (right ventricular systolic pressure
      [RVSP], 36 to 45 mm Hg), 66 patients with moderate PAH (RVSP, 46 to 55 mm Hg),
      and 92 patients with severe PAH (RVSP > or =56 mm Hg). A 52% increase in risk of
      PAH was demonstrated for every 10 years of age at disease onset (odds ratio [OR],
      1.52; 95% confidence interval [CI], 1.31 to 1.76). In addition, there was a
      twofold greater risk of PAH (OR, 2.30; 95% CI, 1.32 to 3.99) for late-onset (age
      > or =60 years) vs earlier-onset (< 60 years) disease. These associations
      remained evident and were somewhat strengthened when the analyses were restricted
      to patients with moderate and severe PAH. CONCLUSIONS: We identified increasing
      age at scleroderma onset as a risk factor for PAH. Vigilance among these high
      risk patients may provide an opportunity to intervene prior to development of
      irreversible pulmonary vascular disease.

PMID- 14665487
TI  - Polymerase chain reaction of pleural biopsy is a rapid and sensitive method for
      the diagnosis of tuberculous pleural effusion.
AB  - BACKGROUND: Tuberculous pleural effusion occurs in 30% of patients with
      tuberculosis (TB). Rapid diagnosis of a tuberculous pleural effusion would
      greatly facilitate the management of many patients. Polymerase chain reaction
      (PCR) has been used to detect Mycobacterium tuberculosis in pleural fluid with
      highly variable sensitivity. OBJECTIVE: To improve our laboratory diagnosis of
      tuberculous pleural effusion. METHODS: We applied PCR to detect DNA specific for
      M tuberculosis in 33 of the studied pleural biopsy specimens using an IS986-based
      primer that was specific for mycobacterium complex, and compared it to the
      results of pleural fluid and biopsy cultures performed on either Lowenstein
      Jensen (LJ) medium or BACTEC 12B liquid medium (Becton Dickinson Microbiology
      Systems; Cockeysville, MD), Ziehl-Neelsen (ZN) staining, and histopathology in 45
      patients with pleural effusion. RESULTS: Of the 45 patients with pleural effusion
      who were studied, 26 patients received diagnoses of tuberculous pleural effusion
      that had been confirmed by either culture and or histopathology, 10 patients
      received diagnoses of exudative effusion due to causes other than TB, and 9
      patients received diagnoses of transudative effusion. Histopathology of the
      pleural biopsy specimen had a sensitivity of 53.8%. The sensitivity of the ZN
      staining of pleural fluid and biopsy specimens was 0.0% and 3.8%, respectively.
      The sensitivity of the culture on both BACTEC 12B liquid medium and LJ medium was
      higher in pleural biopsy specimens (92.3%) than in pleural fluid specimens
      (15.4%; p > 0.001). The improvements of the BACTEC culture system improved and
      shortened the detection time of M tuberculosis in pleural biopsy specimens. PCR
      of pleural biopsy specimens had 90% sensitivity and 100% specificity. The
      positive predictive value and the negative predictive value for pleural biopsy
      specimen cultures were 100% and 90.5% vs 100% and 86.7% for pleural biopsy
      specimen PCRs. CONCLUSION: The overall accuracy of PCR of pleural biopsy was
      similar to the results of pleural biopsy culture, however, PCR of the pleural
      biopsy was much faster in reaching diagnosis. PCR of pleural biopsy is a useful
      method when used in combination with the BACTEC culture system and
      histopathologic examination of pleural biopsy to reach a rapid diagnosis of
      tuberculous pleural effusion.

PMID- 14665488
TI  - Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of
      latent tuberculosis infection among patients with silicosis in Hong Kong.
AB  - OBJECTIVE: To compare the adverse effects and treatment adherence between 2
      months of rifampin plus pyrazinamide (2RZ) and 6 months of isoniazid (6H).
      BACKGROUND: Patients with silicosis in Hong Kong are at high risk of acquiring
      tuberculosis. A previous study showed that treatment with 6H reduced the risk of
      silico-tuberculosis by one half. METHOD: Patients with silicosis and a Mantoux
      skin test reaction > or =10 mm were randomized to receive either 2RZ or 6H daily.
      Liver function testing was done monthly during the initial 2 months. The adverse
      effects and treatment adherence were compared between the two regimens. RESULTS:
      Forty patients (mean age, 61.6 +/- 9.1 years) and 36 patients (mean age, 57.6 +/-
      9.7 years) were randomized to the 2RZ and 6H arms, respectively (p > 0.05) [+/-
      SD]. Baseline characteristics were comparable. Nineteen patients in the 2RZ arm
      had peak alanine transaminase (ALT) levels > 1.5 times the upper limit of normal
      (ULN) in comparison with only five study subjects of the 6H arm (47.5% vs 13.9%,
      p < 0.01). Fourteen patients (35%) in the 2RZ arm and 1 patient (2.8%) in the 6H
      arm had peak ALT levels more than five times the ULN (p < 0.001). Only seven
      patients had symptoms suggestive of hepatitis; none of the patients had jaundice.
      All recovered after withholding treatment. In the 2RZ study arm, none of the
      baseline characteristics predicted hepatotoxicity. Other adverse effects were
      generally mild and comparable between both study arms. Treatment was stopped
      prematurely in 45% and 36.1% of patients in the 2RZ and 6H arms, respectively (p
      = 0.43). The main reasons were hepatotoxicity for the 2RZ arm and voluntary
      withdrawal after experiencing other minor adverse effects for the 6H arm.
      CONCLUSION: A higher incidence of hepatotoxicity was associated with rifampin
      plus pyrazinamide than isoniazid in the treatment of latent tuberculosis
      infection among patients with silicosis in Hong Kong.

PMID- 14665489
TI  - Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease
      markers in pulmonary sarcoidosis.
AB  - STUDY OBJECTIVES: To determine the discriminative value of serum Clara cell 16
      (CC16), KL-6, and surfactant protein (SP)-D as markers of interstitial lung
      diseases, and their ability to reflect pulmonary disease severity and prognosis
      in sarcoidosis. SUBJECTS: Seventy-nine patients with sarcoidosis and 38 control
      subjects. MEASUREMENTS: Serum CC16, KL-6, and SP-D concentrations at disease
      presentation were measured. Pulmonary function tests and chest radiographs were
      analyzed at presentation and 2-year follow-up. RESULTS: All markers co
      correlated, and a significant difference was found between CC16, KL-6 (Krebs von
      den Lungen-6), and SP-D levels in patients with sarcoidosis and control subjects
      (p < 0.0001). Receiver operating characteristic curve analysis revealed largest
      area under the curve for KL-6. Significantly higher levels of CC16 and KL-6 were
      found in patients with parenchymal infiltration (stage II, III) compared to
      patients without parenchymal infiltration (stage I). In concordance, CC16 and KL
      6 levels inversely correlated with diffusion capacity and total lung capacity,
      and KL-6 also with inspiratory vital capacity. Moreover, higher KL-6 levels were
      weakly but significantly associated with persistence or progression of
      parenchymal infiltrates at 2-year follow-up. CONCLUSION: In this study, KL-6
      appears to be the best discriminative marker in differentiating patients with
      sarcoidosis from healthy control subjects; however, as it is not a specific
      marker for this condition, this quality is unlikely to be useful as a diagnostic
      tool. Both CC16 and KL-6 may be of value in reflecting disease severity, and KL-6
      tends to associate with pulmonary disease outcome.

PMID- 14665490
TI  - The value of flexible transbronchial needle aspiration in the diagnosis of stage
      I sarcoidosis.
AB  - STUDY OBJECTIVES: Transbronchial lung biopsy (TBLB) during flexible bronchoscopy
      (FB) is the recommended procedure for diagnosing sarcoidosis in most cases,
      although its yield in stage I disease is reported to be not as high as when
      parenchymal involvement is radiologically evident. We undertook this study to
      assess the diagnostic value of transbronchial needle aspiration (TBNA) in
      sarcoidosis presenting with hilar and/or mediastinal lymphadenopathy (stage I).
      DESIGN: Retrospective review of bronchoscopy procedures performed over a 6-year
      period for the diagnostic workup of hilar and/or mediastinal lymphadenopathy, as
      detected by chest radiographs. SETTING: Urban academic hospital. PATIENTS: Fifty
      five patients with hilar and/or mediastinal lymphadenopathy without pulmonary
      abnormalities were included in the analysis. INTERVENTIONS: After chest CT and
      physical examinations, all patients underwent FB with TBNA. Patients thought to
      have clinicoradiologic findings highly consistent with sarcoidosis, as assessed
      by the bronchoscopists performing the procedures, underwent combined TBNA and
      TBLB. RESULTS: A diagnosis of sarcoidosis was established in 32 patients. In the
      remaining 23 patients, other diseases were pathologically diagnosed. Overall,
      TBNA was diagnostic in 23 of 32 patients with sarcoidosis (72%) by showing
      nonnecrotizing granulomas in 28 of 39 lymph node stations sampled (72%). Among
      the 15 patients who were submitted to both TBNA and TBLB, TBNA exclusively
      established the diagnosis in 7 of 15 patients (47% increase in the diagnostic
      rate) and its yield exceeded that of TBLB (11 of 15 patients [73%] vs 6 of 15
      patients [40%], respectively). The association of TBNA and TBLB increased the
      diagnostic yield to 87%. CONCLUSIONS: TBNA may be of great value in the
      diagnostic evaluation of patients with suspected stage I sarcoidosis, and its use
      in association with TBLB should be strongly encouraged. TBNA may also preclude
      the need for further surgical diagnostic procedures in several patients with
      hilar and/or mediastinal adenopathy due to causes other than sarcoidosis.

PMID- 14665491
TI  - Yield of transbronchial needle aspiration in diagnosis of mediastinal lesions.
AB  - STUDY OBJECTIVES: To determine the transbronchial needle aspiration (TBNA) yield
      for procedures performed by fellows in training, and the predictors of positive
      TBNA yield at our center. DESIGN: Retrospective chart review. SETTING: A tertiary
      teaching hospital. PATIENTS: One hundred seventy patients who underwent
      fiberoptic bronchoscopy with TBNA of mediastinal lesions from January 1991 to
      July 1999. RESULTS: Final diagnoses were available for 166 patients. TBNA was
      diagnostic in 104 patients (61%) and nondiagnostic in 66 patients (39%). Of 170
      cases, 123 patients (72%) had malignancies, 30 patients (18%) had benign disease,
      and 13 patients (8%) were normal. Of 123 malignancies, 85 patients (69%) had a
      positive result by TBNA. Of 30 cases with benign disease, 11 patients (37%) had
      positive TBNA findings. Eight of 13 patients (62%) with a normal diagnosis had
      diagnostic TBNA (normal lymphoid tissue). There were statistically significant
      correlations between TBNA result and cell type of the lesion (p < 0.001), size of
      the lesion (p < 0.05), and type of malignancy (small cell carcinoma more than non
      small cell carcinoma more than lymphoma, p < 0.05). We did not find any
      significant difference for aspiration yield between carinal and tracheal sites (p
      > 0.05). Logistic regression analysis indicated that the presence of malignancy
      is the major determinant of TBNA yield (p = 0.009). In addition, lesion size does
      affect yield after being adjusted for diagnosis (one-sided p = 0.04).
      CONCLUSIONS: TBNA is a minimally invasive diagnostic technique with a high yield,
      even in hands of less experienced operators. Malignancy, lesion size, and type of
      malignancy are major determinants of TBNA yield.

PMID- 14665492
TI  - Clinical feasibility of noncontrast-enhanced magnetic resonance lymphography of
      the thoracic duct.
AB  - STUDY OBJECTIVE: The dilatation of the thoracic duct was previously demonstrated
      in liver cirrhosis by lymphangiography, endoscopic ultrasound, and at autopsy.
      The evaluation of the morphologic change of the thoracic duct may be important in
      assessing the altered lymphodynamics in liver cirrhosis. The objectives of this
      study were to determine which combination of posture and breathing phase during
      noncontrast-enhanced magnetic resonance lymphography (MRL) provided the clearest
      images, and to evaluate the morphologic changes in the thoracic duct in healthy
      volunteers and patients with liver disease and malignancy. DESIGN: Prospective
      study. SETTING: Community general hospital. DESIGN AND SUBJECTS: Twenty-three
      healthy volunteers and 113 patients underwent the MRL examination using a three
      dimensional, half-Fourier, fast spin echo sequence on a 1.5-T, whole-body
      magnetic resonance system. The appropriate posture and breathing phase of MRL to
      obtain the best visualization was first determined by trial on 14 healthy
      volunteers. Morphologic changes of the thoracic ducts were evaluated in 23
      healthy volunteers including the 14 healthy volunteers for the first trial and
      113 patients using this appropriate method. The width of the thoracic ducts in
      both patients and volunteers was measured. MEASUREMENTS AND RESULTS: MRL with
      respiratory gating in the supine position depicted the thoracic duct well and was
      the most comfortable for the subjects. In 82 of 113 patients (72.6%), the
      thoracic ducts were entirely visualized from the diaphragm level to the
      subclavian region. The remaining 31 patients had ducts that could not be entirely
      visualized due to sections or short lengths that were obscured. The maximum
      diameter was 3.74 +/- 0.81 mm in all healthy volunteers, 6.98 +/- 2.77 mm in
      alcoholic cirrhosis, 4.12 +/- 1.51 mm in nonalcoholic cirrhosis, 3.76 +/- 1.10 mm
      in malignancy, and 3.60 +/- 0.80 mm in chronic hepatitis (mean +/- SD). The
      diameter in alcoholic cirrhosis was significantly greater than in other groups (p
      < 0.01). CONCLUSIONS: Respiratory gating in the supine position is the best MRL
      method for acquiring the clearest images. This may be a good method of detecting
      morphologic changes in the thoracic duct. The patients with alcoholic cirrhosis
      showed a greater thoracic duct diameter than other groups.

PMID- 14665493
TI  - Pulmonary cryptococcosis in nonimmunocompromised patients.
AB  - BACKGROUND: Cryptococcus neoformans can cause serious systemic infections
      requiring systemic antifungal therapy in immunocompromised hosts. However,
      isolated pulmonary cryptococcosis in nonimmunocompromised hosts has been reported
      to resolve spontaneously without treatment. STUDY OBJECTIVE: s: To determine the
      role of antifungal therapy in the management of isolated pulmonary cryptococcosis
      in nonimmunocompromised hosts. DESIGN: Retrospective study. SETTING: Tertiary
      care, referral medical center PATIENTS: Thirty-six nonimmunocompromised subjects
      with isolated pulmonary cryptococcosis who received diagnoses at the Mayo Clinic
      (Rochester, MN) from 1976 to 2001. INTERVENTIONS: None. MEASUREMENTS AND RESULTS:
      Of 42 nonimmunocompromised subjects with cryptococcal infections, 36 (86%) had
      isolated pulmonary cryptococcosis. The mean (+/- SD) age of these 36 patients was
      61 +/- 15 years (range, 14 to 88 years), and the groups included 17 men (47%) and
      19 women (53%). Twenty-four patients (67%) were symptomatic, and 12 patients
      (33%) were asymptomatic. The most common presenting symptoms were cough, dyspnea,
      and fever. Cultures of sputum and bronchial washings most commonly yielded the
      diagnosis. Cerebrospinal fluid examination was performed in 11 patients (31%) and
      was negative in all of them. Follow-up information was available on 25 patients
      (69%) with a median duration of 19 months (range, 1 to 330 months). Twenty-three
      of these patients (92%) had resolution of their disease (no treatment, 8
      patients; surgical resection only, 6 patients; and antifungal therapy, 9
      patients). The condition of the two remaining patients had improved. There was no
      documented treatment failure, relapse, dissemination, or death in any of these 25
      patients. CONCLUSIONS: Our findings suggest that an initial period of observation
      without the administration of antifungal therapy is a reasonable option for
      nonimmunocompromised subjects with pulmonary cryptococcosis in the absence of
      systemic symptoms or evidence of dissemination, as well as after surgical
      resection for focal cryptococcal pneumonia.

PMID- 14665495
TI  - Classifying asthma: disagreement among specialists.
AB  - OBJECTIVE: The asthma practice guidelines developed by the National Institutes of
      Health include a system for classifying asthma severity. The goal of the present
      study was to assess the interrater reliability of this classification system by
      measuring agreement among pediatric asthma specialists. DESIGN: A survey
      containing eight case summaries was mailed to 24 board-certified pediatric
      allergists and pulmonologists, who were asked to classify each case according to
      the national guidelines. The case summaries included the patient's medical
      history, physical examination, and chest radiograph and pulmonary function test
      results. Physicians were also asked to interpret the pulmonary function tests, to
      indicate the main factors used to classify each case (daytime symptoms, nighttime
      symptoms, pulmonary function testing, or various combinations), and to make
      treatment recommendations. kappa statistics were used to measure agreement.
      RESULTS: Fourteen of 24 surveys mailed (58%) were completed and returned.
      Agreement was poor for classifying asthma (kappa = 0.29; 95% confidence interval
      [CI], 0.25 to 0.33) and for the main factors used to make the classifications
      (kappa = 0.19; 95% CI, 0.14 to 0.23). Specialists exhibited higher agreement in
      their interpretation of pulmonary function tests (no asthma, kappa = 0.66; asthma
      on baseline, kappa = 0.53; exercise-induced asthma, kappa = 0.65). While
      physicians' treatment recommendations were consistent with their severity
      classifications, the low level of agreement in those classifications led to
      substantial variability in the treatments recommended. CONCLUSIONS: The low level
      of agreement among pediatric asthma specialists in classifying asthma severity
      suggests the need to refine the classification system used in the national
      guidelines to help ensure the consistent application of those guidelines.

PMID- 14665494
TI  - Cost and incidence of social comorbidities in low-risk patients with community
      acquired pneumonia admitted to a public hospital.
AB  - CONTEXT: There are up to 1 million patients treated in acute-care hospitals for
      community-acquired pneumonia (CAP), with an estimated annual cost > 8 billion
      dollars. A newly validated CAP outcomes prediction rule developed by Fine and
      colleagues has been advocated as a guide to hospitalization decisions. OBJECTIVE:
      To evaluate the clinical characteristics, costs of care, and resource utilization
      of patients with low-risk CAP at an urban public hospital serving an indigent
      population. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study from June
      1, 1994 to May 31, 1996. MAIN OUTCOME MEASURES: Clinical characteristics and
      costs of care of patients with low-risk CAP and features associated with low-risk
      CAP in this population. RESULTS: A total of 522 patients were identified at the
      time of hospital admission as having CAP; 97 patients (19%) were HIV positive on
      hospital admission and excluded. Of the remaining 425 patients, 253 patients
      (60%) were classified as pneumonia severity index (PSI) class I-III (low risk).
      Of the patients with low-risk CAP, only four patients (1.6%; 95% confidence
      interval, 0.4 to 4.0%) died during hospitalization. Low-risk CAP was both costly
      and accounted for significant resource use (35.4% of total CAP costs, and 45% of
      all CAP bed days). Of the patients with low-risk CAP, there were 138 patients
      (55%) who could potentially have been treated as outpatients (absence of altered
      mental status, hypotension, hypoxia on hospital admission, or direct ICU
      admission). However, 49% of these patients had a history of alcoholism, 20% had a
      blood alcohol level > 50 mg/dL, and 44% were homeless. CONCLUSIONS: A significant
      proportion of the patients admitted with CAP to a public hospital had low-risk
      CAP and accounted for a significant proportion of the CAP bed days and costs. The
      use of the PSI accurately predicted which patients would be at low risk for
      death; however, the utility of using the PSI to reduce low-risk CAP hospital
      admissions would have been of limited benefit. High rates of homelessness,
      substance abuse, and medical needs not captured in the PSI would preclude many of
      these patients from unsupervised outpatient treatment.

PMID- 14665496
TI  - Overall contribution of chest wall hyperinflation to breathlessness in asthma.
AB  - BACKGROUND: Studies suggest that the increased volume of both abdominal and rib
      cage compartments of the chest wall contribute to dyspnea during methacholine
      induced airway narrowing. MATERIAL: Eight male patients with asthma aged 34 +/-
      13 years (mean +/- SD) before and during methacholine challenge. METHODS: The
      volume of the chest wall (Vcw), volume of the abdomen (Vab), and volume of the
      rib cage (Vrc) were measured by using a three-dimensional optoelectronic
      plethysmography. RESULTS: During methacholine challenge, the increase in end
      expiratory Vcw (Vcw,ee) [0.55 +/- 0.23 L, p < 0.001] was due to increased Vrc
      (0.37 +/- 0.20 L, p < 0.01) and, to a lesser extent, Vab (0.18 +/- 0.10 L, p <
      0.005). Linear univariate regression analysis showed that changes in dyspnea
      (Borg scale) with the highest methacholine dose correlated with both DeltaFEV(1)
      and DeltaVcw,ee. Multiple regression analysis with the Borg score as dependent
      variable and all other ventilatory indexes as independent variables showed that
      DeltaVcw,ee and DeltaFEV(1) were the only significant contributors to the Borg
      score. Taken together Vcw,ee and FEV(1) explained 56% of variance in the Borg
      score (r(2) = 0.56), although Vcw,ee explained 48% of it. CONCLUSIONS: During
      methacholine challenge in patients with asthma, the overall increase in Vcw,ee is
      a better predictor of dyspnea that the reduction in FEV(1).

PMID- 14665497
TI  - Responsiveness to three bronchial provocation tests in patients with asthma.
AB  - STUDY OBJECTIVES: To compare a new bronchial provocation test, the mannitol
      challenge, with cold air and histamine challenges to demonstrate airway
      hyperresponsiveness (AHR) in patients with difficult-to-diagnose asthma. DESIGN:
      A prospective study. PARTICIPANTS: Thirty-seven consecutive patients with
      recently diagnosed, steroid-naive, mild, or atypical asthma fulfilling the
      diagnostic criteria of Finnish Social Insurance Institution, and 10 healthy
      control subjects. INTERVENTIONS: Each subject completed a symptom questionnaire
      and underwent spirometry, diffusion capacity measurement, skin-prick tests, and
      bronchial provocations with mannitol, histamine, and cold air. The severity of
      asthma was classified according to the Global Initiative for Asthma (GINA).
      RESULTS: Fifty-one percent of the asthmatic patients responded to mannitol (> or
      =15% fall in FEV(1)), 24% to cold air (> or =9% fall in FEV(1)), and 81% or 49%
      to histamine (provocative dose causing a 15% fall in FEV(1) [PD(15)] < 1.0 mg or
      < 0.4 mg, respectively). None of the healthy control subjects responded. The GINA
      classification was not associated with responsiveness to any of the challenges.
      CONCLUSIONS: Mannitol is more sensitive than cold air in demonstrating AHR in
      patients with mild or atypical asthma. Histamine was more sensitive than both
      mannitol and cold air if 1.0 mg was used as a cut-off value for histamine PD(15).
      However, if the cut-off value for histamine PD(15) is lowered to 0.4 mg, which
      represents a specific diagnosis of asthma according to previous studies, the
      sensitivity values of mannitol and histamine challenges are comparable.

PMID- 14665498
TI  - Effect of guaifenesin on cough reflex sensitivity.
AB  - BACKGROUND: Guaifenesin, a commonly used agent for the treatment of cough, is
      termed an expectorant since it is believed to alleviate cough discomfort by
      increasing sputum volume and decreasing its viscosity, thereby promoting
      effective cough. Despite its common usage, relatively few studies, yielding
      contrasting results, have been performed to investigate the action and efficacy
      of guaifenesin. STUDY OBJECTIVES: To evaluate the effect of guaifenesin on cough
      reflex sensitivity. DESIGN: Randomized, double-blind, placebo-controlled trial.
      SETTING: Academic medical center. PARTICIPANTS: Fourteen subjects with acute
      viral upper respiratory tract infection (URI) and 14 healthy volunteers.
      INTERVENTIONS: On 2 separate days, subjects underwent capsaicin cough challenge 1
      to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched
      placebo. MEASUREMENTS AND RESULTS: The concentration of capsaicin inducing five
      or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log
      C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14,
      respectively (p = 0.028). No effect on cough sensitivity was observed in healthy
      volunteers. CONCLUSIONS: Our results demonstrate that guaifenesin inhibits cough
      reflex sensitivity in subjects with URI, whose cough receptors are transiently
      hypersensitive, but not in healthy volunteers. Possible mechanisms include a
      central antitussive effect, or a peripheral effect by increased sputum volume
      serving as a barrier shielding cough receptors within the respiratory epithelium
      from the tussive stimulus.

PMID- 14665499
TI  - The breathlessness, cough, and sputum scale: the development of empirically based
      guidelines for interpretation.
AB  - BACKGROUND: A patient report of respiratory symptoms in COPD is essential to
      successfully monitoring disease, adjusting treatment, and evaluating outcomes.
      OBJECTIVE: To develop empirically based guidelines for interpreting mean changes
      in symptom scores using the Breathlessness, Cough, and Sputum Scale (BCSS).
      METHODS: Analyses were performed on data from three multinational trials (n =
      2,971). Mean changes in BCSS score with treatment were examined by physician and
      patient ratings of treatment efficacy, juxtaposed with percentage change in
      symptoms, statistical effect size (ES), DeltaFEV(1), and change in St. George
      Respiratory Questionnaire (SGRQ) score. BCSS scores during an exacerbation were
      examined relative to changes in peak expiratory flow and rescue medication use.
      RESULTS: Mean baseline BCSS total score was 5.2 +/- 2 (+/- SD); 90% of scores
      were between 2 and 9. Highly efficacious treatment (n = 257; physician rating)
      was associated with a DeltaBCSS total score of - 1.3 +/- 1.8, representing a 24%
      improvement (ES = 0.7), and corresponding to a 10% improvement in FEV(1) and
      DeltaSGRQ score total of - 10.3 +/- 13.8. Similar changes in BCSS score were
      observed during recovery from an exacerbation (n = 713; - 1.3 +/- 1.8). Mean
      change with moderately efficacious treatment (n = 965) was - 0.7 +/- 1.8, a 13%
      improvement (ES = 0.3) corresponding to DeltaSGRQ total score of - 6.8 +/- 12.6.
      Mildly efficacious treatment (n = 891) was associated with a change of - 0.35, a
      7% improvement (ES = 0.18), with a DeltaFEV(1) <1% and DeltaSGRQ total score of -
      2.6 +/- 11.7. CONCLUSIONS: Patient-reported daily symptom data are sensitive to
      change and useful for both observational studies and controlled clinical trials
      of patients with COPD. A mean DeltaBCSS total score > 1.0 represents substantial
      symptomatic improvement, changes of approximately 0.6 can be interpreted as
      moderate, and changes of 0.3 can be considered small.

PMID- 14665500
TI  - Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a
      12-week, open-label study.
AB  - STUDY OBJECTIVES: The purpose of this 12-week study was to evaluate the efficacy
      and safety of adjunct modafinil to treat excessive sleepiness in patients with
      obstructive sleep apnea (OSA) who experience residual sleepiness despite regular
      nasal continuous positive airway pressure (nCPAP) use. DESIGN: Twelve-week, open
      label trial. SETTING: Twenty-two centers in the United States. PATIENTS: We
      studied 125 patients with moderate-to-severe OSA (ie, respiratory disturbance
      index > or =15) before nCPAP therapy and residual daytime sleepiness (Epworth
      sleepiness scale [ESS] score > or =10) despite effective and regular nCPAP
      therapy. Patients were studied after completing a 4-week, double-blind, placebo
      controlled trial of nCPAP plus modafinil for the treatment of residual daytime
      sleepiness. INTERVENTIONS AND MEASUREMENTS: Patients received individually
      titrated doses of modafinil (200 to 400 mg qd). Sleepiness was assessed using the
      ESS, quality of life was evaluated using the Functional Outcomes of Sleep
      Questionnaire (FOSQ), and the overall clinical effect was indexed using the
      clinical global impression of change scale. Adverse events, nCPAP use, and vital
      sign measurements were also recorded. RESULTS: The significant improvements in
      daytime wakefulness and sleep-related functional status observed with modafinil
      treatment during the 4-week, double-blind study were maintained throughout 12
      weeks of open-label treatment: week 12 ESS, 7.8 (4.7) vs 14.4 (3.1) at double
      blind baseline; week 12 FOSQ, 3.3 (0.6) vs 14.4 (2.7) at double-blind baseline
      (mean [SD]). The percentage of patients rated as clinically improved increased
      from 83% after 1 week to > or =93% after 2 to 12 weeks of open-label treatment.
      Mean (SD) nCPAP use decreased from 6.3 (1.3) h/night at baseline to 5.9 (1.4)
      h/night (p = 0.004) during open-label treatment. The most common adverse events
      were headache (28%), anxiety (16%), and nervousness (14%). CONCLUSIONS: Modafinil
      remained effective and well tolerated as an adjunct therapy for residual daytime
      sleepiness even after 12 weeks of daily dosing in patients with OSA receiving
      nCPAP therapy.

PMID- 14665501
TI  - Oral continuous positive airway pressure for sleep apnea: effectiveness, patient
      preference, and adherence.
AB  - BACKGROUND: Nasal continuous positive airway pressure (CPAP) is the most
      definitive medical therapy for obstructive sleep apnea (OSA). Many patients have
      difficulty tolerating nasal CPAP due to nasal airway problems, mouth leak, and
      general discomfort from the mask and headgear. These limitations may be overcome
      by an oral mask (Oracle; Fisher & Paykel Healthcare; Languna Hills, CA) that does
      not require headgear. We performed a study to compare the Oracle mask to
      conventional nasal and oronasal masks in the effectiveness of CPAP delivery and
      patient satisfaction and adherence. METHODS: Ninety-eight, consecutive CPAP-naive
      patients with OSA diagnosed by overnight polysomnography (apnea-hypopnea index
      [AHI] > 5) were referred for CPAP therapy. All patients were presented with a
      variety of CPAP masks, including nasal, oronasal, and Oracle, and reasons for
      mask choice were documented. After 3 weeks of acclimatization to the mask of
      their choice, patients had a CPAP titration sleep study to determine their
      optimal CPAP level. Further follow-up was obtained 2 months and 6 months later
      with a subjective patient assessment of CPAP use and efficacy, mask comfort, and
      upper airway dryness. RESULTS: Patients were predominantly male (70%), middle
      aged (50.6 +/- 11.7 years), and moderately obese (body mass index, 32.5 +/- 9.0)
      with severe OSA (AHI, 40.6 +/- 25.8/h) [mean +/- SD]. Patients were classified
      into three groups based on their choice of mask: nasal (66%), Oracle (27%), and
      oronasal (7%). Baseline characteristics did not differ significantly between
      groups. Optimal CPAP was not significantly different between mask groups (nasal,
      7.7 +/- 2.1 cm H(2)O; Oracle, 8.0 +/- 2.0 cm H(2)O; oronasal, 9.7 +/- 3.2 cm
      H(2)O; p = 0.267). Subjective ratings of adherence, efficacy, and mask comfort
      were also similar between groups. However, the Oracle group had more complaints
      of upper airway dryness and "rain-out." The oronasal group had a
      disproportionately greater number of dropouts from CPAP therapy than the Oracle
      group (57% vs 19%, p = 0.046). Nine patients changed from the Oracle mask to a
      nasal mask during the study, whereas no patients changed from their nasal or
      oronasal masks. CONCLUSIONS: The Oracle mask is an efficacious interface for long
      term CPAP therapy in patients with OSA. The main limitations of the mask are
      upper airway dryness and rain-out associated with heated humidification, which
      may be improved by further technical modifications. Oracle may be more acceptable
      than oronasal masks for patients who cannot rely exclusively on the nasal airway
      for CPAP therapy.

PMID- 14665502
TI  - Impact of nasal continuous positive airway pressure therapy on the quality of
      life of bed partners of patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) improves daytime
      sleepiness and quality of life in patients with obstructive sleep apnea syndrome
      (OSAS). However, few studies have examined the impact of treatment on the quality
      of life of bed partners of these patients. METHODS: We prospectively studied 55
      couples in which one person (the patient) had OSAS diagnosed and was subsequently
      commenced on CPAP therapy; 45 of these couples shared a bed on a regular basis.
      Both partner and patient completed postal questionnaires immediately prior to
      CPAP therapy and again after a median of 8 weeks (interquartile range [IQR], 6 to
      12 weeks) of therapy at home. Questionnaires consisted of the Epworth sleepiness
      scale (ESS), the UK Short Form-36 health survey, and the hospital anxiety and
      depression scale. No intervention or advice was given to the partner of the
      patient receiving CPAP therapy. RESULTS: In addition to the expected significant
      benefits reported by patients receiving CPAP, bed partners also reported
      significant improvements in ESS scores (median, 4 [IQR, 1 to 8.5] before CPAP;
      median, 2 [IQR, 1 to 5] during CPAP), in addition to measures of anxiety, role
      limitation due to physical problems, role limitation due to emotional problems,
      social functioning, mental health, and energy/vitality (all p < 0.05 by Wilcoxon
      signed rank testing). CONCLUSIONS: These data support the hypothesis that
      partners of patients with OSAS benefit significantly from the CPAP therapy their
      bed partners receive.

PMID- 14665503
TI  - Longitudinal determinants of peak aerobic performance in children with cystic
      fibrosis.
AB  - BACKGROUND: Several cross-sectional studies in patients with cystic fibrosis (CF)
      have shown that nutritional status and lung function are important determinants
      of peak aerobic capacity (peak oxygen uptake [O(2)peak]). In order to account for
      individual changes, the aim of this study was to determine the longitudinal
      relationship of changes in nutritional status, lung function, and O(2)peak in
      children with CF. DESIGN AND METHODS: Fat-free mass (FFM), lung function, and
      O(2)peak were assessed in 65 children with CF at baseline (mean +/- SD age, 10.5
      +/- 2.9 years; mean FEV(1), 92.6 +/- 20.5%) and again 2 years later. FFM was
      calculated using skinfold thickness, and O(2)peak was measured using an
      incremental treadmill test for children < 12 years old or an incremental cycle
      ergometry test for children > or =12 years old. Lung function was measured before
      the exercise test. RESULTS: Over the 2-year study period, an increase was found
      for absolute values of FFM (6.1 kg, p < 0.001), FEV(1) (229 mL, p < 0.001), and
      O(2)peak (240 mL, p < 0.001), while a decrease was found for predicted values of
      FEV(1) (- 8.9%, p < 0.001) and O(2)peak (- 4.4%, p < 0.05). DeltaO(2)peak over
      the 2-year period best correlated with DeltaFEV(1) (r = 0.619, p < 0.001) and to
      a lesser degree with DeltaFFM (r = 0.506, p < 0.001). Multiple regression
      analysis demonstrated that DeltaFEV(1) and DeltaFFM explained 47% of the
      variation of the DeltaO(2)peak over the 2-year period. CONCLUSIONS: Our results
      show that longitudinal changes in O(2)peak are associated with changes in lung
      function and to a lesser extent with changes in nutritional status in children
      with CF. Special consideration should be given to exercise training and
      nutritional intervention, which might improve long-term clinical outcome in
      children with CF.

PMID- 14665504
TI  - Hidden depletion of fat-free mass and bone mineral density in adults with cystic
      fibrosis.
AB  - BACKGROUND: Weight loss is associated with reduced survival in patients with
      cystic fibrosis (CF). OBJECTIVE: We hypothesized that some adult patients with a
      normal body mass index (BMI) have evidence of hidden fat-free mass (FFM) and bone
      mineral density (BMD) depletion that is linked to more severe disease. DESIGN:
      Fat mass (FM), FFM, and BMD were determined by dual-energy x-ray absorptiometry
      (DXA) and by bioelectric impedance in 56 adults in clinically stable condition
      and 20 age-matched healthy subjects. FM index and FFM index (FFMI) [kilograms per
      meter squared] of the right arm, leg, and trunk (ratio to height squared) were
      calculated. Lung function, including the maximum inspiratory pressure (MIP) and
      sustained MIP (SMIP), physical activity, serum C-reactive protein (CRP) and the
      number of exacerbations in the previous year were recorded. RESULTS: Patients had
      a lower total FFM than healthy subjects (p < 0.01), while FM was similar. Of the
      56 patients, 30 patients had a normal BMI, of which 12 patients had a low FFM
      (hidden loss) by DXA. The right arm, leg, and trunk FFMI and BMD at hip sites
      were less in these patients than in those with a normal BMI and normal FFM (all p
      < 0.01). This group had a lower FEV(1), SMIP, more frequent exacerbations, and
      greater circulating CRP (all p < 0.05). CONCLUSIONS: In adults with CF, apparent
      or hidden loss of FFM, rather than weight loss, was related to overall disease
      severity. Hidden depletion of FFM was associated with increased loss of BMD and
      systemic inflammatory activity.

PMID- 14665505
TI  - Pleurodesis practice for malignant pleural effusions in five English-speaking
      countries: survey of pulmonologists.
AB  - BACKGROUND: Pleurodesis is important in the management of malignant pleural
      effusions, but no consensus exists on the optimal agent or methods of
      pleurodesis. How pleurodesis is practiced worldwide has not been studied.
      OBJECTIVES: To identify variations in the clinical practice of pleurodesis in
      major English-speaking countries, and to quantify the experience of
      pulmonologists on the effectiveness and adverse effects of different pleurodesis
      agents worldwide. METHODS: Eight hundred fifty-nine pulmonologists practicing in
      the United States, United Kingdom, Canada, Australia, and New Zealand
      participated in a Web-based survey. RESULTS: The respondents collectively perform
      > 8,300 pleurodesis annually. Talc was the preferred agent by most respondents
      (slurry, 56%; poudrage, 12%), followed by tetracycline derivatives (26%), and
      bleomycin (7%). Differences were seen in pleurodesis practice patterns among
      practitioners among and within the surveyed countries. Physicians' overall
      satisfaction with the available pleurodesis agents was modest (5.0 out of 8), and
      the reported success rate averaged only 66%. Talc (both poudrage and slurry) was
      perceived as significantly more effective, but was associated with significantly
      more pain, nausea, and fever (p < 0.05). Respiratory failure occurred more
      commonly with talc poudrage than with other agents (p < 0.05), and had been
      observed by 70% and 54% of physicians who used talc poudrage and slurry,
      respectively. CONCLUSIONS: Significant variations exist in how pleurodesis is
      performed worldwide. Pleurodesis agents currently available are perceived as
      suboptimal. Talc poudrage and slurry were perceived to be more effective, but
      were associated with more complications, including respiratory failure.

PMID- 14665506
TI  - Incidence, etiology, and outcome of nosocomial pneumonia in ICU patients
      requiring percutaneous tracheotomy for mechanical ventilation.
AB  - OBJECTIVE: To determine the epidemiology of pneumonia in patients with
      tracheotomy receiving short-term mechanical ventilation. DESIGN: Observational
      prospective study. SETTING: A 14-bed medical-surgical ICU. SUBJECTS: Ninety-nine
      critically ill acute patients requiring percutaneous dilatational tracheotomy for
      mechanical ventilation. INTERVENTIONS: Tracheal aspirate obtained 48 h before
      tracheotomy. MEASUREMENTS AND MAIN RESULTS: Eighteen patients (18.1%) acquired
      pneumonia (median of 7 days after tracheotomy). Pseudomonas aeruginosa was the
      most frequently identified pathogen, found in eight of the episodes (four not
      documented by prior tracheal colonization), followed by other Gram-negative
      bacilli. The development of ventilator-associated pneumonia (VAP) was not
      anticipated by any clinical variable. A positive tracheal aspirate (TA) culture
      result obtained before tracheotomy was associated with a risk of acquiring
      pneumonia of 19.7%, whereas sterile TA cultures were associated with a risk of
      14.3% (p > 0.20). VAP prolonged ICU stay or the ventilation period for a median
      of 19 days and 15 days, respectively. Overall mortality was 34.3%, but the
      presence of VAP did not increase the mortality rate. CONCLUSIONS: Percutaneous
      tracheotomy in patients receiving short-term mechanical ventilation predisposes
      to pneumonia. Pneumonia was associated with prolonged ventilation and ICU stay,
      but was not associated with increased mortality. Pseudomonas is a common pathogen
      after tracheotomy, and this observation should be considered in selecting an
      antibiotic regimen, because TA obtained prior to the tracheotomy often failed to
      identify this pathogen.

PMID- 14665507
TI  - Determinants of candidemia and candidemia-related death in cardiothoracic ICU
      patients.
AB  - STUDY OBJECTIVES: To develop and prospectively validate models of independent
      predictors of candidemia and candidemia-related death in cardiothoracic ICU
      (CICU) patients. DESIGN: (1) An initial, prospective, one-center, case-control,
      independent predictor-model determining study; and (2) a prospective, two-center,
      model-validation study. SETTING: The initial study was performed at the 14-bed
      CICU of the Onassis Cardiac Surgery Center, Athens, Greece; the model-validation
      study was performed at the Onassis Cardiac Surgery Center CICU and the 12-bed
      CICU of Henry Dunant General Hospital, Athens, Greece. PATIENTS: In the initial
      study, 4,312 patients admitted to the Onassis Center CICU between March 1997 and
      October 1999 were considered for enrollment; 30 candidemic and 120 control
      patients (case/control ratio, 1/4) matched according to potential confounders
      were ultimately enrolled. In the model-validation study, 2,087 patients admitted
      to the Onassis and Henry Dunant CICUs between November 1999 and May 2002 were
      prospectively enrolled. MEASUREMENTS AND RESULTS: Models of predictors of
      candidemia and associated death were constructed with stepwise logistic
      regression and subsequently validated. Independent candidemia predictors were
      ongoing invasive mechanical ventilation (IMV) > OR =10 days, hospital-acquired
      bacterial infection and/or bacteremia, cardiopulmonary bypass duration > 120 min,
      and diabetes mellitus. Model performance was as follows: sensitivity,
      53.3%/57.9%; specificity, 100%/100%; positive predictive value (PPV), 100%/100%;
      negative predictive value (NPV), 88.9%/99.6%; and accuracy, 90.1%/99.6%
      (initial/model-validation study values, respectively). IMV > or =10 days and
      hospital-acquired bacterial infection/bacteremia were the two strongest
      candidemia predictors. APACHE (acute physiology and chronic health evaluation) II
      score > or =30 at candidemia onset independently predicted candidemia-related
      death with 80.0%/85.7% sensitivity, 80%/75% specificity, 66.7%/66.7% PPV,
      88.9%/88.9% NPV, and 80.0%/78.9% accuracy (initial/model-validation study values,
      respectively). CONCLUSIONS: We provided a set of easily determinable independent
      predictors of the occurrence of candidemia in CICU patients. Our results provide
      a rationale for implementing preventive measures in the form of independent
      predictor control, and initiating antifungal prophylaxis in high-risk CICU
      patients.

PMID- 14665508
TI  - The effect of vasopressin on gastric perfusion in catecholamine-dependent
      patients in septic shock.
AB  - OBJECTIVE: To study the effect of continuous infusion of vasopressin on the
      splanchnic circulation in patients with severe septic shock. DESIGN: Prospective
      clinical study. SETTING: ICU in a teaching hospital. PATIENTS: Eleven consecutive
      patients with documented septic shock who remained hypotensive despite
      norepinephrine infusion at a rate > or =0.2 microg/kg/min. INTERVENTIONS:
      Insertion of a gastric tonometry catheter, and continuous infusion of vasopressin
      0.04 U/min during 4 h. MEASUREMENTS AND MAIN RESULTS: Difference between gastric
      and arterial CO(2) partial pressure (P[g-a]CO(2) gap), mean arterial pressure,
      and cardiac index were recorded at baseline and after 15 min, 30 min, 60 min, 120
      min, and 240 min. RESULTS: The median P(g-a)CO(2) gap increased from 5 mm Hg at
      baseline to 19 mm Hg after 4 h (p = 0.022). Mean arterial pressure increased from
      61 +/- 13 mm Hg at baseline to 68 +/- 9 mm Hg after 4 h (p = 0.055). No
      significant changes in cardiac index were noted. CONCLUSIONS: In norepinephrine
      dependent patients in septic shock, continuous infusion of low-dose vasopressin
      results in a significant increase of the P(g-a)CO(2) gap compatible with GI
      hypoperfusion.

PMID- 14665509
TI  - Pulmonary contusion in severe head trauma patients: impact on gas exchange and
      outcome.
AB  - STUDY OBJECTIVE: To evaluate the impact on morbidity and mortality of pulmonary
      contusion in multiple-trauma patients with severe head trauma. DESIGN: Matched
      paired, case-control study SETTING: ICU at a tertiary university hospital.
      PATIENTS: During a 3-year period, 313 consecutive multiple-trauma patients with
      severe head trauma (Glasgow coma scale [GCS], </= 8) who were admitted to the
      ICU. INTERVENTIONS: Case-control matching criteria were as follows: (1) age
      difference within 5 years; (2) sex; (3) GCS in two categories; (4) similar
      pattern of injury; and (5) simplified acute physiology score II in five
      categories. A pulmonary contusion, defined by the clinical context and the result
      of a chest CT scan, was diagnosed in 90 patients. Analysis was performed on 90
      pairs who were matched with 100% success. RESULTS: Ninety patients (29%)
      presented a diagnosis of pulmonary contusion. The presence of pulmonary contusion
      had an impact on the PaO(2)/fraction of inspired oxygen (FIO(2)) ratio, which was
      significantly reduced in patients with a pulmonary contusion. The ICU stay, the
      occurrence of complications such as nosocomial pneumonia or ARDS, the Glasgow
      outcome scale, and the mortality rate did not significantly differ between case
      patients and control subjects. Mortality also was not affected when patients were
      stratified according to the severity of the PaO(2)/FIO(2) ratio. CONCLUSION: In
      the study patients, pulmonary contusion alters gas exchange but does not appear
      to increase the morbidity and mortality of multiple-trauma patients with head
      trauma. A sample-size effect may limit the interpretation of the study.

PMID- 14665510
TI  - Underrecognition of preexisting cognitive impairment by physicians in older ICU
      patients.
AB  - OBJECTIVES: Cognitive impairment increases with age, as do many serious illnesses
      requiring intensive care. Little is known, however, about physician recognition
      of preexisting cognitive impairment in the ICU and which patient factors may play
      a role in physician recognition. DESIGN: Cross-sectional comparative study.
      SETTING: Urban university teaching hospital. PARTICIPANTS: A total of 165
      patients aged > or =65 years who were admitted to the medical ICU. MEASUREMENTS:
      Two previously validated proxy measures of cognitive impairment, the modified
      Blessed dementia rating scale and the informant questionnaire on cognitive
      decline in the elderly. Physician interviews and medical record abstraction were
      used to evaluate the recognition of cognitive impairment. RESULTS: The prevalence
      of preexisting cognitive impairment in the ICU was 37%. Attending physicians were
      unaware of the preexisting cognitive impairment in 53% of cases, and intern
      physicians were unaware in 59% of cases. The recognition of preexisting cognitive
      impairment increased as the severity of the cognitive impairment increased. Two
      independent risk factors were identified that were significantly associated with
      the increased recognition of preexisting cognitive impairment (ie, impairment in
      activities of daily living or being admitted to the ICU from a nursing home). If
      both were present, preexisting cognitive impairment was 13 times more likely to
      be recognized. CONCLUSIONS: A substantial number of older ICU patients have
      preexisting cognitive impairment on admission to the ICU, and ICU physicians
      caring for these patients are unaware of this cognitive impairment in the
      majority of cases. Future research is needed to identify outcomes related to
      preexisting cognitive impairment and to improve its recognition.

PMID- 14665511
TI  - Practice variation in respiratory therapy documentation during mechanical
      ventilation.
AB  - STUDY OBJECTIVES: Implementation of new ventilatory strategies such as lung
      protective ventilation for ARDS will require a multidisciplinary approach with
      considerable physician and respiratory therapy (RT) interaction. One of the key
      factors in this communication is complete and accurate RT documentation of
      ventilator settings. Few studies have explored the quality and variability of
      this documentation. DESIGN: Population-based cross-sectional study. SETTING:
      Seventeen adult hospitals in King County, WA. PARTICIPANTS/INTERVENTIONS: We
      compared the blank RT ICU flow sheet for each institution to the 1992 American
      Association for Respiratory Care (AARC) clinical practice guidelines (CPGs) for
      patient-ventilator system checks. We interviewed RT managers at each hospital
      about their practices. Finally, we reviewed selected charts of patients with
      acute lung injury (ALI) or ARDS from each hospital to evaluate the documentation.
      MEASUREMENTS/RESULTS: We found substantial variability in RT documentation
      practices and in their extent of compliance with the AARC CPGs. Only 15 of 52
      items recommended by the AARC CPGs were included on blank RT flow sheets of every
      hospital in our study, and only 26 of 52 items were found on charts of ALI/ARDS
      patients at most hospitals (ie, > or =10 of 17 hospitals). Only 10 of 17 RT
      department managers reported using the AARC CPGs as a basis for their
      documentation policies. Items necessary for the implementation of lung-protective
      ventilation for ALI/ARDS patients were recorded inconsistently and were not
      included in the AARC CPGs. Plateau pressure was found on all reviewed charts of
      ALI/ARDS patients at only 10 of 17 hospitals. CONCLUSIONS: Considerable
      variability exists in RT documentation practices. We suggest that new guidelines
      be developed for documenting the care of patients receiving mechanical
      ventilation, in light of recent data on ventilator weaning and the management of
      ALI/ARDS, and that their effect on practice and outcomes be evaluated.

PMID- 14665512
TI  - High expression of p40(tax) and pro-inflammatory cytokines and chemokines in the
      lungs of human T-lymphotropic virus type 1-related bronchopulmonary disorders.
AB  - STUDY OBJECTIVE: Human T-lymphotropic virus type 1 (HTLV-1) is closely associated
      with the development of certain pulmonary diseases, such as bronchiolitis,
      although the pathologic mechanism remains unclear. To elucidate the pathogenesis
      of HTLV-1-associated bronchopulmonary disorders, we analyzed the relationship
      between expression of p40(tax), a regulatory component of HTLV-1 that stimulates
      various host genes, and synthesis of pro-inflammatory cytokines and chemokines by
      cells in BAL fluid (BALF) obtained from HTLV-1-infected patients. DESIGN: Reverse
      transcription-polymerase chain reaction was used to compare the expression of
      p40(tax) and pro-inflammatory cytokines and chemokines messenger RNA (mRNA) in
      BALF of 10 HTLV-1 carriers and 7 healthy subjects. We also studied the
      correlation between these parameters and the proportion of lymphocytes in BALF.
      RESULTS: The expression levels of pro-inflammatory cytokines (interferon [IFN]
      gamma, interleukin-2) and chemokines (monocyte chemotactic protein-1, macrophage
      inflammatory protein [MIP]-1alpha, IFN-gamma-inducible protein-10 [IP-10]) were
      significantly higher in BALF of patients than of healthy subjects. The expression
      of IFN-gamma and MIP-1alpha mRNA correlated with that of p40(tax). IFN-gamma and
      IP-10 mRNA expression correlated with the proportion of lymphocytes in BALF. The
      percentage of lymphocytes in BALF increased with higher expression levels of
      p40(tax) mRNA, although the correlation was not significant. CONCLUSION: Our
      results suggested that p40(tax) seems be involved in the development of HTLV-1
      associated bronchopulmonary disorders at least in part through the local
      production of pro-inflammatory cytokines and chemokines.

PMID- 14665513
TI  - Effect of inhaled NG-nitro-L-arginine methyl ester on Candida-induced acute lung
      injury.
AB  - STUDY OBJECTIVES: Nitric oxide (NO) and peroxynitrite play a crucial role in
      acute lung injury (ALI). Whether NO synthase (NOS) inhibition is beneficial in
      the treatment of lung injury remains controversial. The objective of this study
      was to test the hypothesis that local inhibition of NOS in the lung reduces lung
      injury. DESIGN: We developed a model of Candida-induced ALI in the mouse by IV
      injection of Candida albicans. To evaluate the effect of NOS inhibitor, mice were
      pretreated by inhalation of saline solution or N(G)-nitro-L-arginine methyl ester
      (L-NAME) before induction of Candida-induced ALI. MEASUREMENTS AND RESULTS: After
      inhalation of 1 mM aerosolized L-NAME, nitrite-nitrate concentrations in BAL
      fluid (BALF) were significantly lower at 24 h and 48 h than those in mice treated
      with C albicans alone. Tumor necrosis factor-alpha, interleukin-1beta, and
      macrophage inflammatory protein-2 concentrations in lung homogenates, measured by
      enzyme-linked immunosorbent assay, and neutrophil counts in BALF were decreased
      by inhalation of L-NAME (n = 6 per group). Immunohistochemical analysis of
      inducible NOS (iNOS) and nitrotyrosine, a major product of protein nitration by
      peroxynitrite, revealed that alveolar macrophages and alveolar epithelial cells
      were positive for both substances in Candida-induced ALI. Inhalation of L-NAME
      markedly suppressed iNOS protein expression and nitrotyrosine production.
      Histologic evidence of lung injury decreased and survival improved after
      inhalation of L-NAME. CONCLUSIONS: We conclude that NO might play a crucial role
      in the pathogenesis of Candida-induced ALI, and such injury might be reduced by
      local inhibition of NOS. Our findings suggest that inhalation of L-NAME is
      beneficial in the treatment of Candida-induced ALI.

PMID- 14665514
TI  - Cumulative effects of aging and mechanical ventilation on in vitro diaphragm
      function.
AB  - STUDY OBJECTIVE: Unloading the diaphragm, via mechanical ventilation (MV),
      results in significant diaphragmatic atrophy, contractile dysfunction, and
      oxidative stress in young adult animals. Since aging increases skeletal muscle
      susceptibility to atrophy and injury, we tested the hypothesis that MV-induced
      diaphragmatic contractile dysfunction would be exacerbated in aging rats.
      METHODS: Fisher 344/Brown Norway hybrid rats (4 months old [young] and 30 months
      old [old]) were assigned to either control or MV groups. MV rats were
      anesthetized, tracheostomized, and ventilated with 21% O(2) for 12 h. Arterial
      BP, pH, and blood gas homeostasis were maintained in the MV animals throughout
      the experimental period. Animals in the control group were acutely anesthetized,
      and the diaphragms were immediately removed. Muscle strips from the mid-costal
      diaphragm were removed from each experimental animal, and contractile properties
      were studied in vitro. RESULTS: Compared to young control animals, aging (old
      control animals) was associated with a 13% decrease in maximal isometric tension
      (24.5 N/cm(2) vs 21.3 N/cm(2)). Although, MV induced similar relative losses
      (24%) in diaphragmatic isometric tension in both young and old animals receiving
      MV, the combined effects of aging and MV resulted in a 34% decrement in
      diaphragmatic isometric tension compared to young control animals (24.5 N/cm(2)
      vs 16.1 N/cm(2)). CONCLUSIONS: These data do not support the hypothesis that
      aging exacerbates the relative MV-induced impairment in diaphragmatic isometric
      tension. Nonetheless, the additive effects of aging and MV have dramatic effects
      on diaphragmatic force reserve. This could exacerbate weaning difficulties in
      older individuals receiving MV.

PMID- 14665515
TI  - The nose and sleep-disordered breathing: what we know and what we do not know.
AB  - The relationship between sleep-disordered breathing (SDB) and nasal obstruction
      is unclear. In order to better understand, we performed an extensive computer
      assisted review and analysis of the medical literature on this topic. Data were
      grouped into reports of normal control subjects, patients with isolated nasal
      obstruction, and those with SDB. We conclude that SDB can both result from and be
      worsened by nasal obstruction. Nasal breathing increases ventilatory drive and
      nasal occlusion decreases pharyngeal patency in normal subjects. Nasal congestion
      from any cause predisposes to SDB. Although increased nasal resistance does not
      always correlate with symptoms of congestion, nasal congestion typically results
      in a switch to oronasal breathing that compromises the airway. Moreover, oral
      breathing in children may lead to the development of facial structural
      abnormalities associated with SDB. We postulate that the switch to oronasal
      breathing that occurs with chronic nasal conditions is a final common pathway for
      SDB.

PMID- 14665516
TI  - Gadolinium-enhanced magnetic resonance angiography for detection of acute
      pulmonary embolism: an in-depth review.
AB  - STUDY OBJECTIVE: To review the published experience with gadolinium-enhanced
      magnetic resonance angiography (MRA) for the detection of acute pulmonary
      embolism (PE) in order to test the hypothesis that gadolinium-enhanced MRA may be
      potentially sensitive and specific enough to include it among diagnostic
      alternatives in the evaluation of patients with suspected PE. METHODS: Studies
      were identified by searching MEDLINE for trials that used gadolinium-enhanced MRA
      to diagnose acute PE based on the visualization of an intraluminal filling defect
      or a cutoff vessel, using pulmonary angiography as a reference standard. RESULTS:
      Twenty-eight investigations were identified in which MRA was used to diagnose PE.
      Only three studies, however, met the criteria for inclusion in the analysis. In
      these three case series, the sensitivity of gadolinium-enhanced MRA ranged from
      77 to 100%, and the specificity ranged from 95 to 98%. CONCLUSION: Gadolinium
      enhanced MRA may be a useful diagnostic alternative in some patients with
      suspected acute PE, particularly if they have an elevated creatinine level, have
      an allergy to radiographic contrast material, or should, if possible, avoid
      exposure to ionizing radiation.

PMID- 14665517
TI  - Systematic review of the evidence regarding potential complications of inhaled
      corticosteroid use in asthma: collaboration of American College of Chest
      Physicians, American Academy of Allergy, Asthma, and Immunology, and American
      College of Allergy, Asthma, and Immunology.
AB  - INTRODUCTION: The available clinical guidelines have been successful in improving
      awareness of the inflammatory nature of asthma and have promoted the use of
      inhaled corticosteroids (ICSs) to achieve long-term control of symptoms. Because
      of lingering concerns over the possible adverse consequences of ICS use, an
      expert panel was convened with a mandate to identify the critical questions that
      impact decisions regarding the use of ICSs and to evaluate the available evidence
      with respect to risk. METHODS: A university librarian retrieved citations and
      abstracts from the MEDLINE and EMBASE databases using a list of National Library
      of Medicine search terms and key words. Reviewers were asked to systematically
      abstract relevant information from each of their assigned articles and to list
      their own clinical or scientific conclusions based on the study results. A
      predefined grading algorithm was used to calculate a summary quality rating score
      for the relevant evidence. RESULTS: The results are presented as a series of key
      questions followed by a summary of the relevant evidence. An evidence grade is
      assigned, followed by a summary statement reflecting the panel's consensus
      opinion following review. CONCLUSIONS: The preponderance of evidence supports a
      conclusion that the proven clinical effectiveness of ICS treatment decidedly
      outweighs the proven risks.

PMID- 14665518
TI  - Pancreatitis-associated acute lung injury: new insights.

PMID- 14665519
TI  - Top ten list in pleural disease.

PMID- 14665520
TI  - Elimination of the left atrial appendage to prevent stroke or embolism? Anatomic,
      physiologic, and pathophysiologic considerations.
AB  - The "elimination" of the left atrial appendage (LAA) seems to be an attractive
      alternative to oral anticoagulation in the treatment of atrial fibrillation,
      especially in patients with contraindications to oral anticoagulation therapy.
      The LAA, however, plays an important role in the maintenance and regulation of
      the cardiac function, in arterial hypertension, atrial fibrillation, coronary
      heart disease, valvular heart disease, and heart failure. Data, mainly from
      animal studies, indicate that elimination of the LAA may impede thirst in
      patients with hypovolemia, may impair hemodynamic response to volume or pressure
      overload, may decrease cardiac output, and may promote heart failure. It may have
      adverse effects in humans as well. Further studies on the hemodynamic and
      neurohumoral consequences of left atrial appendage elimination are required to
      advance our understanding of LAA physiology and pathophysiology.

PMID- 14665521
TI  - Intracardiac (superior vena cava/right atrial) ECGs using saline solution as the
      conductive medium for the proper positioning of the Shiley hemodialysis catheter:
      is it not time to forego [correction of forgo] the postinsertion chest
      radiograph?
AB  - Hemodialysis (HD) is often administered in critical care areas to patients with
      chronic renal failure as a continuation of the HD they are receiving on an
      ambulatory basis, and to patients who develop such a need for the first time or
      may require HD only transiently. The double-lumen Shiley central venous catheter
      (SCVC), inserted via the brachiocephalic veins, is often employed for HD, and it
      is customary to obtain a chest radiograph to ensure proper positioning of the tip
      of the SCVC within the superior vena cava (SVC) or high right atrium (RA). This
      practice is implemented to evaluate for complications stemming from the insertion
      of the SCVC and subsequent mishaps due to low positioning of the tip of the
      catheter in the RA or right ventricle. Intracardiac ECGs obtained via a saline
      solution-filled SCVC as the conductive medium can be easily recorded serially and
      periprocedurally to ensure proper positioning of the tip of the SCVC in the SVC
      or high RA based on the evaluation of the appearance and amplitude of atrial
      depolarization, thus rendering chest radiographs redundant.

PMID- 14665522
TI  - Thoracoscopic appearance of bilateral spontaneous pneumothorax.
AB  - STUDY OBJECTIVES: We investigated the macroscopic features of bilateral
      pneumothorax (BLP) and compared them with those of unilateral pneumothorax (ULP).
      METHODS: Surgical cases of spontaneous pneumothorax (236 cases) were divided into
      two groups based on unilateral occurrence (206 cases) or bilateral occurrence (30
      cases). The patients were divided into three groups by the macroscopic findings
      of lung disease. The first group consisted of those patients with solitary and
      small bullae (type I pneumothorax), the second group consisted of those with
      multiple and large bullae (type II pneumothorax), and the third group consisted
      of those with an aggregation of diffuse and tiny bullae (type III pneumothorax).
      RESULTS: In metachronous BLP cases, 18 patients (66.7%) revealed type III
      pneumothorax in the first occurrence site, and 13 of 18 patients (72.2%) revealed
      type III pneumothorax in the contralateral site. Type III pneumothoraces were
      more frequently found in patients with BLP (18 of 27 patients; 66.7%) compared
      with ULP (73 of 206 patients; 35.4%; p = 0.0086 [chi(2) test]). During a follow
      up ranging from 12 to 129 months (median, 69 months), 7 patients (23.3%) in the
      BLP group developed recurrences. This rate was higher than that of the ULP group
      (5.3%; p = 0.0009 [chi(2) test]). Contralateral CT scan findings of their first
      occurrence were retrospectively reviewed. In 3 patients (15.8%) in the BLP group
      and 17 patients (12.3%) in the ULP group, apical lung bullae and blebs (ruptured
      or intact) could be detected on the contralateral lung (p = 0.703 [chi(2) test]).
      CONCLUSIONS: The patients with an aggregation of diffuse and tiny bullae in their
      thoracoscopic findings had a high risk of contralateral recurrence. Macroscopic
      lung appearance in the contralateral site in such patients tended to reveal the
      same type as that in the primary site. CT scanning was not useful for predicting
      the risk of contralateral occurrence.

PMID- 14665523
TI  - Outcome of occupational asthma in patients with continuous exposure: a 3-year
      longitudinal study during pharmacologic treatment.
AB  - STUDY OBJECTIVE: To evaluate the effect of treatment with beclomethasone
      dipropionate (500 microg bid) and salmeterol (50 microg bid) on lung function and
      respiratory symptoms in 20 subjects with occupational asthma (OA) still exposed
      to the work environment cause of their disease. METHODS: At enrollment and every
      6 months for 3 years, respiratory symptom score (from 0 [no symptoms] to 2
      [moderate-to-severe symptoms]), spirometry, methacholine challenge, peak
      expiratory flow (PEF) variability, and the use of rescue salbutamol were
      evaluated. During the 3 years of follow-up, 10 subjects were excluded from the
      study because they retired or changed jobs. MEASUREMENTS AND RESULTS: Symptoms of
      work-related asthma started 12.6 +/- 13.1 years (mean +/- SD) before diagnosis.
      At baseline, mean FEV(1) was 80.2% of predicted values and provocative dose of
      methacholine causing a 20% fall in FEV(1) (PD(20)) was 1,001 +/- 1,275 microg;
      the workers received 2.1 +/- 2.4 puffs of salbutamol per day. After 3 years, no
      significant differences in any of the morbidity outcomes (FEV(1), PD(20), PEF
      variability, use of rescue salbutamol, respiratory symptom score) were found as
      compared with baseline or run-in values. CONCLUSIONS: Regular treatment with
      inhaled corticosteroids and long-acting bronchodilators seems to prevent
      respiratory deterioration over a 3-year period in workers with mild-to-moderate
      persistent OA who were still exposed at work to the environmental cause of their
      disease.

PMID- 14665524
TI  - Adaptation of pulmonary oxygen consumption slow component following 6 weeks of
      exercise training above and below the lactate threshold in untrained men.
AB  - STUDY OBJECTIVES: To examine the effects of 6 weeks of exercise training above or
      below the lactate threshold (LT) on the slow component (SC) of pulmonary oxygen
      consumption (.VO(2)). DESIGN: Randomized controlled trial. SETTING: University
      human performance laboratory. PARTICIPANTS: Apparently healthy, untrained men (n
      = 18). INTERVENTIONS: Subjects were randomized to one of three groups: high
      intensity exercise training (HI) [above the LT], moderate-intensity exercise
      training (MOD) [below the LT], or no exercise training (CON). Exercise groups
      performed cycle ergometry 4 d/wk for 6 weeks. Total work throughout training was
      constant between groups. MEASUREMENTS AND RESULTS: Maximal cycle ergometry was
      performed at baseline and after training to assess power output at the LT (WLT),
      .VO(2) at the LT (.VO(2)LT), and peak .VO(2) (.VO(2)PK). High-intensity, constant
      load cycling was performed at baseline and weeks 1, 2, 4, and 6 to assess SC
      adaptations. WLT, .VO(2)LT, and .VO(2)PK increased after 6 weeks in both exercise
      groups compared to the CON group (p < 0.05), although there were no differences
      between the training groups. SC of .VO(2) decreased 44% in the HI group following
      1 week of exercise training vs MOD (20%, p < 0.05) and CON (12%, p < 0.01)
      groups. The SC attenuation was more prominent at all time points in the HI group
      compared to the MOD group. Total SC attenuation over the 6-week training period
      did not differ between the HI (71%) and MOD (57%) groups. CONCLUSIONS: Training
      at HI or MOD produced similar improvements in the LT, .VO(2), and power output at
      peak exertion when total work output was held constant. Attenuation of the SC
      with training above and below the LT were similar, although above-LT training
      promoted faster SC adaptations.

PMID- 14665525
TI  - A 74-year-old man with bilateral pulmonary opacities and rapidly progressive
      renal failure.

PMID- 14665526
TI  - Respiratory distress in woman who began complaining of dyspnea and cough 5 months
      ago.

PMID- 14665527
TI  - Opacified hemithorax with ipsilateral mediastinal shift after transthoracic
      needle biopsy.

PMID- 14665528
TI  - Endobronchial ultrasonography in the diagnosis and treatment of relapsing
      polychondritis with tracheobronchial malacia.
AB  - Relapsing polychondritis (RP) with tracheobronchial involvement has a poor
      prognosis, and a delay in diagnosis increases morbidity and mortality; however,
      the diagnosis is difficult to make. Endobronchial ultrasonography (EBUS) revealed
      changes in the tracheobronchial cartilage in two patients who met the criteria
      for RP, and facilitated the diagnosis. In these cases, EBUS revealed a poorly
      defined bronchial wall structure with two patterns of cartilaginous damage:
      fragmentation and edema. These cases were successfully treated by the
      implantation of nitinol stents, the sizes of which were determined by EBUS. EBUS
      was found to be useful in the diagnosis and treatment of RP.

PMID- 14665529
TI  - Pulmonary cryptococcosis after initiation of anti-tumor necrosis factor-alpha
      therapy.
AB  - Many patients with rheumatoid arthritis are being treated with immunosuppressive
      regimens that include an agent directed at blocking tumor necrosis factor (TNF)
      alpha. Although reportedly safe, tuberculous and fungal infections have emerged
      as significant complications of therapy. We report a case of pulmonary
      cryptococcosis soon after the initiation of therapy with the anti-TNF-alpha
      antibody, infliximab. A diagnosis was made early in the disease course, and the
      patient responded quickly to antifungal therapy. This case should alert
      clinicians to the increased incidence of pulmonary mycoses in patients receiving
      anti-TNF-alpha therapy.

PMID- 14665530
TI  - Successful treatment of primary pulmonary angiosarcoma.
AB  - Angiosarcoma in the lung is an uncommon disorder and is usually attributable to
      metastasis from a primary site. Primary pulmonary angiosarcoma is extremely rare,
      and the prognosis of affected individuals is dismal, with most patients dying
      within months of presentation. Indeed, there have been no reported instances of
      successful treatment of this condition. We now report the case of a patient with
      primary pulmonary angiosarcoma who responded to a combination of radiotherapy and
      immunotherapy with recombinant interleukin-2. The patient remains well without
      signs of recurrence 1 year after initial presentation. This combination therapy
      may be a promising strategy to prolong the survival of patients with primary
      pulmonary angiosarcoma.

PMID- 14665531
TI  - Diffuse alveolar hemorrhage after allogeneic hematopoietic stem-cell
      transplantation: treatment with recombinant factor VIIa.
AB  - Diffuse alveolar hemorrhage (DAH) is a serious pulmonary complication that occurs
      in patients undergoing hematopoietic stem-cell transplantation (HSCT). Current
      management strategies are limited to corticosteroids, platelet transfusions, and
      mechanical ventilator support to treat acute respiratory failure. Recombinant
      factor VIIa (rFVIIa) is an approved agent for the treatment of bleeding in
      patients with hemophilia A or B and the presence of inhibitors. We report a case
      of DAH after allogeneic HSCT that failed standard therapy and was then
      successfully treated with rFVIIa.

PMID- 14665532
TI  - Idiopathic pulmonary fibrosis in transplantation.

PMID- 14665533
TI  - Urine color testing and isoniazid monitoring.

PMID- 14665534
TI  - Interferons and their application in lung diseases.

PMID- 14665535
TI  - Mice are resistant to the induction of a pleurodesis.

PMID- 14665536
TI  - Symptoms in cardiac myxoma.

PMID- 14665537
TI  - Distal intestinal obstruction syndrome after surgery in cystic fibrosis.

PMID- 14665538
TI  - Cigarette smoking, asthma, and emphysema.

PMID- 14665539
TI  - Does the predicted postoperative FEV1 formula reflect the real value?

PMID- 14665543
TI  - Is there any alternative to the Bispectral Index Monitor?

PMID- 14665544
TI  - Does epidural analgesia improve surgical outcome?

PMID- 14665545
TI  - The latest changes... no more shorts.

PMID- 14665546
TI  - Does bispectral analysis of the electroencephalogram add anything but complexity?
AB  - BACKGROUND: Analysis of the bispectrum of EEG waveforms is a component of the
      proprietary BIS index-a commonly used commercial monitor of depth of anaesthesia.
      Does the use of the bispectrum give more information about depth of anaesthesia
      than the power spectrum? METHODS: We collected and analysed EEG waveforms during
      induction of general anaesthesia in 39 patients, comparing the changes in
      bispectral parameter (SynchFastSlow), with an analogous power spectrum-based
      parameter (PowerFastSlow). Both compare the logarithmic ratio of high frequency
      components (40-47 Hz) with the total (1-47 Hz). Because the changes in bispectrum
      are affected by signal amplitude, we also calculated a third parameter (SFSbicoh)
      from the bicoherence, which is an amplitude-independent statistic. RESULTS: The
      SynchFastSlow and PowerFastSlow were correlated (r=0.84) and neither was superior
      in predicting the awake or anaesthetized state (area under receiver operating
      characteristic curves = 0.85 vs 0.93). There was no change in the SFSbicoh over
      the induction period, and it did not correlate with SynchFastSlow (r=0.07).
      CONCLUSIONS: We could not show that bispectral analysis gave more information
      than power spectral-based analysis. Most of the changes in the bispectral values
      result from decreases in the relative high frequency content of the EEG caused by
      anaesthesia.

PMID- 14665547
TI  - The Bispectral Index in children: comparing isoflurane and halothane.
AB  - BACKGROUND: The Bispectral Index (BIS) has been calibrated for several general
      anaesthetic agents including isoflurane. Halothane is still used in paediatric
      anaesthesia. Compared with other volatile anaesthetics, halothane has a different
      receptor affinity and differing effects on the EEG. There are limited data
      evaluating the BIS with halothane. We set out to compare the BIS using halothane
      and isoflurane at a clinically relevant equipotent concentration (1 MAC) and at a
      reproducible measure of anaesthetic effect (awakening). METHODS: Forty children
      aged between 2 and 15 yr were enrolled in a masked randomized trial-20 in each
      group. Anaesthesia was induced with sevoflurane or propofol. Either halothane or
      isoflurane were given to obtain an end-tidal concentration of 1 MAC for 15 min.
      The BIS was then recorded. The BIS was also recorded at awakening. Values (mean
      (SD)) were compared with a t test. RESULTS: At 1 MAC the BIS for halothane was
      significantly greater than isoflurane (56.5 (8.1) vs 35.9 (8.5), P<0.0001). At
      awakening there was no significant difference (BIS halothane; 81.1 (11.9), BIS
      isoflurane; 82.5 (16.4)). The difference in means at awakening was 1.4 (95% CI 
      8.2 to 11.1). CONCLUSIONS: At equipotent concentrations of halothane and
      isoflurane BIS valves were significantly greater with halothane. At awakening the
      BIS values were equivalent for each agent. This finding is consistent with the
      BIS being more affected by the agent used at higher concentrations of
      anaesthetic. The BIS must be interpreted with caution when using halothane.

PMID- 14665548
TI  - Evoked EEG patterns during burst suppression with propofol.
AB  - BACKGROUND: During EEG suppression with isoflurane or sevoflurane anaesthesia,
      median nerve stimulation causes cortical responses of two kinds: an N20 wave with
      a latency of 20 ms and an EEG burst with a latency of 200 ms. We tested the
      possibility that median nerve stimulation during EEG suppression with propofol
      would cause an EEG response that was consistent enough to be of use for
      neuromonitoring. METHODS: Eight patients were anaesthetized with propofol to
      allow burst suppression. Electrical stimulation of the median nerve was applied
      during general anaesthesia and the EEG was measured. RESULTS: The EEG response to
      a painful stimulus had four successive components: (i) N20 and P22 potentials,
      reflecting activation of fast somatosensory pathways; (ii) a high-amplitude
      negative wave, possibly reflecting activation of the somatosensory cortex SII
      bilaterally; (iii) a burst (i.e. a negative slow wave with superimposed 10 Hz
      activity, probably reflecting an arousal mechanism); and (iv) a 13-15 Hz spindle,
      probably originating from the thalamus, similar to sleep spindles. These could be
      seen separately and in different combinations. Bursts and spindles during burst
      suppression were also seen without stimulation. In deepening propofol
      anaesthesia, spindles were seen in the continuous EEG before burst suppression
      was achieved. In deep anaesthesia, spindles were seen when bursts had ceased, and
      painful stimuli evoked sharp waves without subsequent bursts. CONCLUSION: In
      addition to SSEP (somatosensory evoked potentials), three different evoked
      responses are noted that could be useful for clinical monitoring.

PMID- 14665549
TI  - Mid-latency auditory evoked response during propofol and alfentanil anaesthesia.
AB  - BACKGROUND: Propofol has been shown to affect the mid-latency auditory evoked
      response (MLAER) in a dose-dependant manner. Few studies have investigated the
      addition of alfentanil. Myogenic responses, such as the post-auricular responses
      (PAR), can confound the MLAER but there has been little investigation as to which
      electrode site reduces this interference. METHODS: We studied the MLAER in 27
      women. They received an infusion of alfentanil 15 micro g kg(-1) h(-1), followed
      by either a high or low infusion regimen of propofol (final infusion rates 6 and
      3 mg kg(-1) h(-1)). We compared the results with those of our study using
      propofol alone. We collected the data from two electrode sites: vertex-inion and
      vertex-mastoid. We evaluated the occurrence of the PAR and the shape of the MLAER
      at each electrode site. RESULTS: The infusion rate of propofol associated with
      loss of the eyelash response in 50% of subjects was 3.3 mg kg(-1) h(-1). This was
      significantly lower than using propofol alone (5.8 mg kg(-1) h(-1)). Nb latency
      was the best MLAER discriminator of unconsciousness (sensitivity 94%, specificity
      88%), with a threshold of 46 ms (propofol alone was 53 ms). The addition of
      alfentanil did not alter the relationship between propofol infusion rate and
      MLAER. The vertex-inion electrode site gave the best protection against PAR in
      awake subjects (P=0.0003), and after 30 min of propofol infusion (P=0.06). The
      magnitude of the MLAER obtained from the vertex-mastoid electrodes was larger
      than from the other site, although the increase was not consistent throughout the
      waveform (brain stem 100%, Nb 14%). CONCLUSIONS: Addition of alfentanil lowers
      the propofol infusion rate required to produce unconsciousness and the Nb latency
      that predicts it. The better of the two sites to reduce the incidence of PAR is
      the vertex-inion electrode site.

PMID- 14665550
TI  - Changes in cortical electrical activity during induction of anaesthesia with
      thiopental/fentanyl and tracheal intubation: a quantitative
      electroencephalographic analysis.
AB  - BACKGROUND: There are regional differences in the effects of anaesthetics agents
      and perioperative stimuli on the EEG. We studied the topography of the EEG during
      induction of anaesthesia and intubation in patients receiving thiopental and
      fentanyl to document regional electrical brain activity. METHODS: EEG was
      recorded in 25 patients in the awake state, after pre-medication, during
      induction, at loss of consciousness and after intubation. Eight bipolar
      recordings were made and the relative power of the frequency bands delta, theta,
      alpha, and beta were used (after z-score transformation for age) to measure
      changes in regional EEG activity. RESULTS: Noxious stimulation during tracheal
      intubation partially reversed the slowing of the EEG caused by anaesthesia.
      During induction of anaesthesia alpha activity was most reduced in temporal and
      occipital regions. The most prominent EEG changes after intubation were an
      increase in alpha and a decrease in delta power (P<0.001). The largest changes
      were in the frontal and temporal leads for alpha and in the frontal and central
      leads for delta. Heart rate and arterial pressure remained constant during
      intubation. CONCLUSIONS: Changes in alpha and delta power were identified as the
      most sensitive EEG measures of regional changes in electrical brain activity
      during anaesthesia and noxious stimulation.

PMID- 14665551
TI  - Effects of ephedrine, dobutamine and dopexamine on cerebral haemodynamics:
      transcranial Doppler studies in healthy volunteers.
AB  - BACKGROUND: Sympathomimetic drugs are assumed to have no direct effects on
      cerebral haemodynamics on the basis of animal experiments; there is little
      evidence of their direct effects in humans. This study aimed to address this
      issue. METHODS: The effects of ephedrine, dobutamine, and dopexamine on cerebral
      autoregulation, cerebral vascular reactivity to carbon dioxide, estimated
      cerebral perfusion pressure, and zero flow pressure (ZPF) were studied in 10
      healthy volunteers using transcranial Doppler ultrasound. The strength of
      autoregulation was measured using the transient hyperaemic response test. The
      reactivity to carbon dioxide was measured as the change in middle cerebral artery
      flow velocity with a step change in end-tidal carbon dioxide. For the estimated
      cerebral perfusion pressure and the ZFP, established formulae were used which
      utilized instantaneous values of arterial pressure and middle cerebral artery
      flow velocity. Measurements were made at baseline and after i.v. infusion of the
      study drug to an endpoint of 25% increase in mean arterial pressure (MAP)
      (ephedrine, dobutamine) or cardiac index (dopexamine). RESULTS: There was no
      significant change in the strength of autoregulation (from (mean (SD)) 1.07
      (0.16) to 1.07 (0.18); from 1.07 (0.16) to 1.03 (0.19); from 1.04 (0.12) to 1.04
      (0.25)), reactivity to carbon dioxide (from 40% (8) to 36 (10); from 37 (12) to
      37 (11); from 45 (12) to 43 (11)) with ephedrine, dobutamine, or dopexamine,
      respectively. Despite a clinically significant increase in MAP with ephedrine and
      dobutamine and a clinically significant increase in cardiac index with
      dopexamine, the estimated cerebral perfusion pressure did not change
      significantly (from 81 (38) to 60 (16) mm Hg with ephedrine; from 67 (22) to 63
      (11) mm Hg with dobutamine; from 87 (27) to 79 (17) mm Hg with dopexamine). The
      ZFP increased significantly with ephedrine (from 29 (10) to 44 (11) mm Hg) and
      dobutamine (from 35 (14) to 43 (10) mm Hg) but not dopexamine (from 3 (23) to 11
      (22) mm Hg). CONCLUSIONS: Sympathomimetic agents do not significantly change
      cerebrovascular homeostasis as assessed by the transient hyperaemic response
      test, reactivity to carbon dioxide and estimated cerebral perfusion pressure.

PMID- 14665552
TI  - Derivation of preliminary three-dimensional pharmacophoric maps for chemically
      diverse intravenous general anaesthetics.
AB  - BACKGROUND: The molecular basis of i.v. general anaesthetic activity was
      investigated using comparative molecular field analysis (CoMFA). METHODS: The
      free plasma concentrations that abolish movement to a noxious stimulus for 14
      structurally diverse i.v. anaesthetics were obtained from the literature. The
      compounds were randomly divided into a training set (n=10) to derive the activity
      model, and a separate test set (n=4) used to assess its predictive capability.
      The anaesthetic structures were aligned so as to maximize their similarities in
      molecular shape and electrostatic potential to conformers of the most active
      agent in the group, eltanolone. The conformers and alignments that showed the
      maximum similarity (calculated using combined Carbo indices) were retained, and
      used to derive the CoMFA models. RESULTS: The final model explained 94.0% of the
      variance in the observed activities of the training set (n=10, P<0.0001) and was
      a good predictor of test set activity (n=4, r(2)=0.799). In contrast, a model
      based on non-polar solubility (LogP) explained only 78.3% of the variance in the
      observed activities of the training set (n=10, P=0.0007) and was a poor predictor
      for the test set (n=4, r(2)=0.272). Further analysis of the CoMFA results
      identified the spatial distribution of key areas where steric and electrostatic
      interactions are important in determining the activity of the 14 anaesthetics
      considered. CONCLUSIONS: A single activity model can be formulated for i.v.
      general anaesthetics and preliminary pharmacophoric maps derived, which describe
      the molecular basis of their in vivo potency.

PMID- 14665553
TI  - Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to
      clinical acid-base disorders.
AB  - BACKGROUND: The Fencl-Stewart approach to acid-base disorders uses five equations
      of varying complexity to estimate the base excess effects of the important
      components: the strong ion difference (sodium and chloride), the total weak acid
      concentration (albumin) and unmeasured ions. Although this approach is
      straightforward, most people would need a calculator to use the equations. We
      proposed four simpler equations that require only mental arithmetic and tested
      the hypothesis that these simpler equations would have good agreement with more
      complex Fencl-Stewart equations. METHODS: We reduced two complex equations for
      the sodium-chloride effect on base excess to one simple equation: sodium-chloride
      effect (meq litre(-1))=[Na(+)]-[Cl(-)]-38. We simplified the equation of the
      albumin effect on base excess to an equation with two constants: albumin effect
      (meq litre(-1))=0.25x(42-[albumin]g litre(-1)). Using 300 blood samples from
      critically ill patients, we examined the agreement between the more complex Fencl
      Stewart equations and our simplified versions with Bland-Altman analyses.
      RESULTS: The estimates of the sodium-chloride effect on base excess agreed well,
      with no bias and limits of agreement of -0.5 to 0.5 meq litre(-1). The albumin
      effect estimates required log transformation. The simplified estimate was, on
      average, 90% of the Fencl-Stewart estimate. The limits of agreement for this
      percentage were 82-98%. CONCLUSIONS: The simplified equations agree well with the
      previous, more complex equations. Our findings suggest a useful, simple way to
      use the Fencl-Stewart approach to analyse acid-base disorders in clinical
      practice.

PMID- 14665554
TI  - Randomized study comparing the effects of hydroxyethyl starch solution with
      Gelofusine on pulmonary function in patients undergoing abdominal aortic aneurysm
      surgery.
AB  - BACKGROUND: Restoring blood flow to ischaemic tissue can cause lung damage with
      pulmonary oedema. Hydroxyethyl starch (HES) solution, when used for volume
      replacement, may modify and reduce the degree of ischaemia-reperfusion injury. We
      compared the effects of HES solution with those of Gelofusine solution on
      pulmonary function, microvascular permeability and neutrophil activation in
      patients undergoing elective infrarenal abdominal aortic aneurysm surgery.
      METHODS: Forty patients were randomized into two groups. The anaesthetic
      technique was standardized. Lung function was assessed with the PO(2)/FI(O(2))
      ratio, respiratory compliance, chest x-ray and a score for lung injury.
      Microvascular permeability was determined by measuring microalbuminuria.
      Neutrophil activation was determined by measurement of plasma elastase. RESULTS:
      Four hours after surgery, the median (quartile values) PO(2)/FI(O(2)) ratio was
      40.3 (37.8, 53.1) kPa for the HES-treated patients compared with 33.9 (31.2,
      40.9) kPa for the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The
      respiratory compliance was 80 (73.5, 80) ml cm(-1) H(2)O in the HES-treated
      patients compared with 60.1 (50.8, 73.3) ml cm(-1) H(2)O in the Gelofusine
      treated patients (P<0.01, Mann-Whitney test). The lung injury score 4 h after
      surgery was less for the patients treated with HES compared with the patients
      treated with Gelofusine (0.33 vs 0.71, P=0.01, Wilcoxon rank sum test). Mean (SD)
      plasma elastase was less in the HES-treated patients on the first postoperative
      day (1.96 (0.17) vs 2.08 (0.24), P<0.05). The log mean microalbuminuria was less
      in the HES-treated patients (0.41 vs 0.91 mg mmol(-1), P<0.05). This difference
      in microvascular permeability was associated with different volumes of colloid
      required to maintain stable cardiovascular measurements in the two groups of
      patients studied (3000 vs 3500 ml, P<0.01, Mann-Whitney test). CONCLUSION:
      Compared with Gelofusine, the perioperative pulmonary function of patients
      treated with HES after abdominal aortic aneurysm surgery was better.

PMID- 14665555
TI  - Preoperative saline versus gelatin for hip fracture patients; a randomized trial
      of 396 patients.
AB  - BACKGROUND: The aim of this study was to determine if the preoperative
      administration of 500 ml of a gelatin colloid solution intravenously before hip
      fracture surgery improves outcome, compared with a conventional i.v. fluid regime
      with a crystalloid solution. METHODS: Randomized, double blind, controlled trial
      of i.v. saline vs colloid for 396 patients having hip fracture surgery admitted
      to a district general hospital. Patients were followed up for 1 yr. RESULTS:
      There was no statistically significant difference between groups for mortality
      (30-day mortality 9/198 for saline group vs 19/198 for colloid group, 95%
      confidence intervals 0.21-1.02), length of hospital stay (22.5 days vs 17.3 days,
      95% CI -10.78 to 0.38), or occurrence of postoperative complications.
      CONCLUSIONS: The inclusion of 500 ml of colloid solution to the i.v. fluid regime
      before hip fracture surgery does not improve outcome.

PMID- 14665556
TI  - Outcome of ASA III patients undergoing day case surgery.
AB  - BACKGROUND: Day case surgery is becoming more acceptable, even for patients with
      complex medical conditions. Current recommendations suggest that patients who are
      graded as American Society of Anaesthesiologists physical status (ASA) III may be
      suitable for this approach. There is only a small amount of published data
      available to support this. We present a retrospective review of ASA III patients
      who had undergone day surgical procedures in our unit. METHODS: We carried out a
      retrospective case controlled review of 896 ASA III patients who had undergone
      day case procedures between January 1998 and June 2002 using the existing
      computerized patient information system. The system records admission rates,
      unplanned contact with healthcare services and post-operative complications in
      the first 24 h after discharge. RESULTS: We demonstrated no significant
      differences in unplanned admission rates, unplanned contact with health care
      services, or post-operative complications in the first 24 h after discharge
      between ASA III and ASA I or II patients. CONCLUSION: With good pre-assessment
      and adequate preparation ASA III patients can be treated safely in the day
      surgery setting.

PMID- 14665557
TI  - Applied anatomy of the superior vena cava-the carina as a landmark to guide
      central venous catheter placement.
AB  - BACKGROUND: Cardiac tamponade is a serious complication of central venous
      catheter (CVC) insertion. Current guidelines strongly advise that the CVC tip
      should be located in the superior vena cava (SVC) and outside the pericardial
      sac. This may be difficult to verify as the exact location of the pericardium
      cannot be seen on a normal chest x-ray. The carina is an alternative radiographic
      marker for correct CVC placement, suggested on the basis of studies of embalmed
      cadavers. METHODS: We set out to confirm this radiographic landmark in 39 fresh
      cadavers (age 58.4 (3.4) (mean and SE) yr) and to compare the results with those
      from ethanol-formalin-fixed cadavers. RESULTS: We found that the carina was 0.8
      (0.05) cm above the pericardial sac as it transverses the SVC. In no case was the
      carina inferior to the pericardial reflection and our study confirmed the
      previous findings. All the measured distances were significantly greater in fresh
      cadavers. CONCLUSIONS: We confirm that the carina is a reliable, simple
      anatomical landmark that can be identified in vivo for the correct placement of
      CVCs outside the boundaries of the pericardial sac.

PMID- 14665558
TI  - Shortcomings of cuffed paediatric tracheal tubes.
AB  - BACKGROUND: The goal of this investigation was to evaluate adequacy of the design
      of readily available paediatric cuffed tracheal tubes (CPTT). METHODS: In 15
      series of cuffed (11) and uncuffed (four) paediatric tracheal tubes (ID: 2.5-7.0
      mm) from four different manufacturers the following dimensions were measured:
      outer diameter of the tube, position and largest diameter of the tube cuff
      inflated at 20 cm H(2)O and position of depth markings and compared with age
      related dimensions. RESULTS: Outer diameters for tubes with similar IDs varied
      markedly between manufacturers and between cuffed and uncuffed tracheal tubes
      from the same manufacturer. Cuff diameters at 20 cm H(2)O cuff pressure and cross
      sectional cuff area at 20 cm H(2)O cuff pressure did not always cover maximal
      internal age-related tracheal diameters and cross-sectional areas. Placing the
      tube tip in the mid-trachea, the cuffs of cuffed tubes with ID 3.0, 4.0, or 5.0
      mm would become positioned within the larynx. If the cuffs were placed 1 cm below
      the cricoid level, many of the tube tips would be dangerously deep within the
      trachea. Only five of the 11 cuffed tubes had a depth marking. In many of these
      tubes the distances from depth marking to tube tip were greater than the age
      related minimal tracheal length. CONCLUSION: Most cuffed paediatric tracheal
      tubes are poorly designed, in particular the smaller sizes. A better design of
      cuffed tubes with a short high-volume, low-pressure cuff, cuff-free subglottic
      space and adequately placed depth markings are urgently needed.

PMID- 14665559
TI  - Cardiovascular changes during drainage of pericardial effusion by thoracoscopy.
AB  - BACKGROUND: Cardiovascular changes during drainage of pericardial effusion are
      not well understood, and most studies are of systemic effects and not of right
      ventricular performance. Thoracoscopy is not widely used to drain pericardial
      effusions because of haemodynamic changes in relation to the use of single lung
      ventilation. PATIENTS AND METHODS: We studied 16 patients undergoing partial
      pericardiectomy for pericardial effusion, using videothoracoscopy with a low
      pressure pneumothorax (6 mm Hg). Cardiac output was measured by thermodilution
      with the patient anaesthetized in the supine position before the procedure; in
      the right lateral position after a low-pressure pneumothorax had been
      established; and after drainage of the pericardial effusion. RESULTS: Before the
      procedure, cardiac output was low and central venous pressure and pulmonary
      artery occlusion pressure were increased. Systemic vascular resistance and
      arterial blood pressure were within normal limits. Cardiac filling pressure and
      pulmonary arterial pressure increased during the pneumothorax. After the drainage
      cardiac index increased and systemic and pulmonary vascular resistances were
      reduced. CONCLUSIONS: Pericardial effusion reduces right ventricular
      distensibility, right and left systolic ventricular function, and cardiac output.
      Anaesthesia with mechanical ventilation and a low-pressure pneumothorax do not
      affect the circulation greatly. Drainage of the pericardial effusion allows
      cardiac distensibility to increase and cardiac performance changes to allow
      increased ejection.

PMID- 14665560
TI  - Local anaesthetic sensitivities of cloned HERG channels from human heart:
      comparison with HERG/MiRP1 and HERG/MiRP1 T8A.
AB  - BACKGROUND: Myocardial potassium channels are complexes formed by different
      subunits. The subunit composition may influence the cardiotoxic action of local
      anaesthetics. The effects of amide local anaesthetics on HERG channels co
      expressed with the putative subunit MiRP1 have not been established. It is also
      unclear if the common polymorphism MiRP1(T8A) that predisposes individuals to
      drug-induced cardiac arrhythmia increases local-anaesthetic sensitivity of
      HERG/MiRP1 channels. This may suggest the presence of genetic risk factors for
      local-anaesthetic-induced cardiac arrhythmia. METHODS: Whole-cell patch-clamp
      recordings and site-directed mutagenesis were combined to compare local
      anaesthetic sensitivities of cloned and mutated human potassium channel subunits.
      The ion channels were activated by a protocol that approximated ventricular
      action potentials. RESULTS: The amide local anaesthetics bupivacaine,
      levobupivacaine and ropivacaine inhibited HERG channels at toxicologically
      relevant concentrations, with IC(50) values of 20 (SEM 2) micro M (n=29), 10 (1)
      micro M (n=40) and 20 (2) micro M (n=49), respectively. Hill coefficients were
      close to unity. There were no indications of qualitative differences in channel
      inhibition between the three anaesthetics. The putative subunit MiRP1 did not
      alter local anaesthetic sensitivity of HERG channels. The common single
      nucleotide polymorphism producing MiRP1(T8A) did not increase local anaesthetic
      sensitivity of HERG/MiRP1 channels. CONCLUSIONS: Amide local anaesthetics target
      HERG and HERG/MiRP1 channels with identical potency. The effects on these ion
      currents may significantly contribute to local-anaesthetic-induced cardiac
      arrhythmia. MiRP1(T8A) does not seem to confer an increased risk of severe
      cardiac side-effects to carriers of this common polymorphism.

PMID- 14665561
TI  - Comparison of the role of endothelin, vasopressin and angiotensin in arterial
      pressure regulation during sevoflurane anaesthesia in dogs.
AB  - BACKGROUND: In this study we aimed to clarify the role of endothelin in arterial
      pressure regulation during anaesthesia with increasing concentrations of
      sevoflurane (1-3 MAC) and compare it with those of vasopressin and angiotensin.
      METHODS: After an awake control period, on different days, six dogs underwent
      each of the following four interventions: sevoflurane anaesthesia alone (1-3
      MAC), sevoflurane after block of either endothelin receptors using tezosentan (3
      mg kg(-1) followed by 3 mg kg(-1) h(-1)), vasopressin V(1a) receptors using
      [d(CH(2))(5)Tyr(Me(2))]AVP (40 micro g kg(--1)) or angiotensin receptors using
      losartan (6 mg kg(-1) h(-1)). Plasma concentrations of endothelin, big
      endothelin, vasopressin and renin were measured. Effects of sevoflurane in the
      presence and absence of the respective receptor block were analysed and compared
      using analysis of variance for repeated measures (ANOVA followed by Fisher's PLSD
      (protected least significant difference) (P<0.05)). RESULTS: Mean arterial
      pressure decreased in a dose-dependent manner with sevoflurane during all
      interventions. At 1 MAC, this decrease was greatest during angiotensin receptor
      block (mean (SEM), -41 (3) mm Hg), intermediate during vasopressin and endothelin
      receptor block (-31 (4) and -30 (2) mm Hg respectively), and least during
      sevoflurane alone (-24 (3) mm Hg). The course of systemic vascular resistance
      mirrored the course of arterial pressure, while cardiac output did not differ
      between groups. Plasma concentrations of endothelin, big endothelin and renin did
      not change during any intervention, whereas vasopressin concentration increased
      from approximately 0.5 to 40 ng litre(-1) at 3 MAC as arterial pressure decreased
      in all groups. CONCLUSIONS: At 1 MAC, angiotensin attenuated the decrease in
      arterial pressure during sevoflurane anaesthesia more than endothelin and
      vasopressin. However, at higher MAC only vasopressin was specifically activated
      to partly compensate for the arterial pressure decrease.

PMID- 14665562
TI  - Obstetric epidurals and chronic adhesive arachnoiditis.
AB  - It has been suggested that obstetric epidurals lead to chronic adhesive
      arachnoiditis (CAA). CAA is a nebulous disease entity with much confusion over
      its symptomatology. This review outlines the pathological, clinical, and
      radiological features of the disease. The proposed diagnostic criteria for CAA
      are: back pain that increases on exertion, with or without leg pain; neurological
      abnormality on examination; and characteristic MRI findings. Using these
      criteria, there is evidence to show that epidural or subarachnoid placement of
      some contrast media, preservatives and possibly vasoconstrictors, may lead to
      CAA. No evidence was found that the preservative-free, low concentration
      bupivacaine with opioid mixtures or plain bupivacaine currently used in labour
      lead to CAA.

PMID- 14665563
TI  - Methicillin resistant Staphylococcus aureus in the critically ill.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is endemic within many
      hospitals worldwide. Critically ill patients on intensive care units have
      increased risk factors making them especially prone to nosocomially acquired
      infections. This review addresses the current situation regarding the evolution
      of MRSA and the techniques for identifying and epidemiologically typing it. It
      discusses specific risk factors, the morbidity and mortality associated with
      critically ill patients, and possibilities for future antibiotic treatments.

PMID- 14665564
TI  - Endotoxaemia during left ventricular assist device insertion: relationship
      between risk factors and outcome.
AB  - BACKGROUND: Endotoxaemia, caused by splanchnic ischaemia during surgery, is
      believed to trigger systemic inflammation and cause postoperative organ
      dysfunction. A relationship between the plasma concentration of endotoxin during
      surgery and known risk factors for postoperative morbidity and mortality (e.g.
      age, abnormal gastric tonometric variables) and adverse outcome after surgery has
      not been demonstrated. METHODS: In a prospective study, the plasma concentration
      of endotoxin was measured in 12 patients undergoing implantation of a left
      ventricular assist device. Automated air gastric tonometry was performed in all
      patients. The relationship between plasma endotoxin concentration, risk factors,
      and postoperative outcome was explored. RESULTS: Carbon dioxide gap increased
      from 0.7 (0.3) to 3.6 (1.6) kPa at the end of surgery. Endotoxin was detected in
      one of 12 patients at baseline and in nine of 12 patients at the end of surgery
      (P=0.003). A high plasma concentration of endotoxin at the end of surgery was
      associated with a higher carbon dioxide gap (r=0.59, P<0.05), and a higher
      postoperative multiple organ dysfunction score (r=0.7, P=0.01). CONCLUSIONS: The
      finding of an association between high intraoperative plasma concentrations of
      endotoxin, abnormal gastric tonometric variables and adverse outcome supports the
      view that endotoxaemia is caused by gut hypoperfusion during surgery and is
      associated with postoperative organ dysfunction.

PMID- 14665565
TI  - Assessment of preoperative fluid depletion using bioimpedance analysis.
AB  - BACKGROUND: Fluid depletion during the perioperative period is associated with
      poorer outcome. Non-invasive measurement of total body water by bioimpedance may
      enable preoperative fluid depletion and its influence on perioperative outcome to
      be assessed. METHODS: Weight and foot bioimpedance were recorded under
      standardized conditions in patients undergoing bowel preparation (n=43) or day
      surgery (n=44). Fifteen volunteers also followed standard nil-by-mouth
      instructions on two separate occasions to assess the variabilities of weight and
      bioimpedance over time. RESULTS: Body weight fell by 1.27 kg (95% CI 1.03-1.50
      kg; P<0.0001) and foot bioimpedance increased by 51 ohm after bowel preparation
      (95% CI 36-66; P<0.0001). Weight change after the nil-by-mouth period in day
      surgery patients (mean -0.22 kg, 95% CI -0.05 to -0.47 kg; P=0.07) correlated (r=
      0.46; P=0.005) with an increase in bioimpedance (16 ohms, 95% CI 5-27 ohms;
      P=0.01). No difference between two separate bioimpedance measurements was seen in
      the volunteer group. CONCLUSIONS: Further work is warranted to determine if
      bioimpedance changes may serve as a useful indicator of perioperative fluid
      depletion.

PMID- 14665566
TI  - No effect of cardiopulmonary bypass on hypnosis in patients anaesthetized with
      propofol and alfentanil.
AB  - BACKGROUND: The effect of cardiopulmonary bypass (CPB) on the level of
      anaesthetic depth has not been studied previously in a randomized way. METHODS:
      We assessed the effect of CPB on the propofol needed to maintain a fixed
      bispectral index score, and on the recovery from anaesthesia in 22 patients
      undergoing coronary artery bypass graft surgery with CPB (on-pump) compared with
      18 patients operated on without CPB (off-pump). Anaesthesia was induced and
      maintained with propofol and alfentanil. Throughout the procedure, the infusion
      rate of propofol was adjusted to keep the BIS value at 40 +/- 5. RESULTS: With
      the off-pump technique, the duration of surgery and anaesthetic administration
      were significantly greater. The need for propofol in proportion to time was
      exactly the same in both groups. During anaesthesia and the first 3 h thereafter,
      the BIS recordings were similar in both groups. No differences were detected in
      the time to awakening or tracheal extubation. CONCLUSIONS: CPB does not affect
      propofol requirements or immediate postoperative recovery compared with the off
      pump technique.

PMID- 14665567
TI  - Supraventricular tachycardia in pregnancy.
AB  - We present four cases of supraventricular tachycardia in pregnancy of varied
      aetiology. Risk factors for the development of supraventricular tachycardia and
      options for obstetric anaesthetic management, during pregnancy, labour, and at
      Caesarean section are discussed. We recommend the use of adenosine as first line
      therapy.

PMID- 14665568
TI  - Use of a ProSeal laryngeal mask airway for airway maintenance during emergency
      Caesarean section after failed tracheal intubation.
AB  - We report the use of the ProSeal laryngeal mask airway to establish and maintain
      the airway during emergency Caesarean section when tracheal intubation had failed
      with conventional laryngoscopy and mask ventilation was difficult. The ProSeal
      laryngeal mask allowed controlled ventilation without gas leak and facilitated
      drainage of the stomach.

PMID- 14665569
TI  - Postoperative nerve irritation syndrome after epidural analgesia in a six-year
      old child.
AB  - Morbidity after paediatric epidural anaesthesia is unusual. We report a case of
      transient nerve root irritation occurring after epidural analgesia for radical
      nephrectomy in a 6-yr-old boy who received a continuous infusion of bupivacaine
      0.1%. The epidural catheter was inserted within the L2-L3 interspace under
      general anaesthesia. Several possible causes are discussed. Mechanical irritation
      of nerve roots by the epidural catheter in the epidural space is the most likely
      cause. Br J Anaesth 2004: 92: 146-8

PMID- 14665570
TI  - Acute heart failure during spinal surgery in a boy with Duchenne muscular
      dystrophy.

PMID- 14665571
TI  - Accuracy of feedback-controlled oxygen delivery into a closed anaesthesia circuit
      for measurement of oxygen consumption.

PMID- 14665572
TI  - Stress in UK intensive care doctors.

PMID- 14665573
TI  - Preservative-free ketamine.

PMID- 14665574
TI  - Diplopia after cataract surgery.

PMID- 14665575
TI  - Intrathecal morphine for coronary bypass grafting.

PMID- 14665576
TI  - Effects of a new modified balanced hydroxyethyl starch preparation (Hextend) on
      measures of coagulation.

PMID- 14665577
TI  - Anaesthesia records-international access.

PMID- 14665578
TI  - Mens corpora e mens sano.

PMID- 14665579
TI  - Clinical governance in sports medicine.

PMID- 14665580
TI  - Cochrane Reviews: new blocks on the kids.

PMID- 14665581
TI  - Relation between isokinetic muscle strength and functional capacity in
      recreational athletes with chondromalacia patellae.
AB  - OBJECTIVES: To investigate the effects of isokinetic exercise on pain and
      functional test scores of recreational athletes with chondromalacia patellae
      (CMP) and to examine the correlation between isokinetic parameters and functional
      tests or pain score. METHODS: The functional ability of 30 recreational athletes
      with unilateral CMP was evaluated using six different tests. Pain scores were
      assessed during daily activities before and after the treatment protocol.
      Isokinetic exercise sessions were carried out at angular velocities of 60 degrees
      /s (25-90 degrees range of flexion) and 180 degrees /s (full range). These
      sessions were repeated three times a week for six weeks. RESULTS: Quadriceps and
      hamstring peak torque, total work, and endurance ratios had improved
      significantly after the treatment, as did the functional parameters and pain
      scores. There was a poor correlation between the extensor endurance ratio and one
      leg standing test. A moderate correlation between the visual analogue scale and
      the extensor endurance ratio or flexion endurance ratio was also found.
      CONCLUSIONS: The isokinetic exercise programme used in this study had a positive
      effect on muscle strength, pain score, and functional ability of knees with CMP.
      The improvement in the functional capacity did not correlate with the isokinetic
      parameters.

PMID- 14665582
TI  - Elastic stable intramedullary nailing of midclavicular fractures in athletes.
AB  - BACKGROUND: Intramedullary fixation of midclavicular fractures may be a better
      option than non-operative treatment for high performance/professional athletes
      because of the potential reduction in recovery time. OBJECTIVES: To evaluate the
      effectiveness of intramedullary fixation in high performance athletes and the
      time required to return to sporting activity. METHODS: Data were taken from a
      prospective study on intramedullary fixation techniques using the elastic stable
      Ti nail (TEN, Synthes) for the treatment of displaced midclavicular fractures,
      initiated in 1996. The patients in 12 cases were classified as high
      performance/professional athletes. These cases were used to evaluate the
      technique specifically in this population. Fractures were classified according to
      the Orthopaedic Trauma Association (OTA) system. Patients were evaluated before
      and after surgery for shoulder function and subjective pain. After the operation,
      radiological assessments documented fracture healing, and clinical outcomes
      scores were obtained. Time required to return to training and competition was
      documented. RESULTS: All fractures were transverse or oblique. Mean (SD) shoulder
      abduction increased from 36.3 (8) degrees before surgery to 154.2 (17) degrees
      afterwards (p<0.001). Mean subjective pain score using a visual analogue scale (0
      100) decreased from 71.7 (18) points before surgery to 19.2 (6) points (p<0.001)
      three days after. There were no complications. Hospital stay averaged 2.9 (1)
      days. Mean delay to resumption of training was 5.9 (1) days, and to resumption of
      competition it was 16.8 (5) days. The mean Constant clinical outcomes score one
      year after hardware removal was 98.3 (2) points. CONCLUSIONS: Intramedullary
      fixation of displaced midclavicular fracture was successful in terms of clinical
      outcome and rapid resumption of sporting activities. This treatment should be
      offered to athletes as an alternative to non-operative treatment.

PMID- 14665584
TI  - Effects of sodium citrate ingestion before exercise on endurance performance in
      well trained college runners.
AB  - OBJECTIVE: To test the hypothesis that sodium citrate administered two hours
      before exercise improves performance in a 5 km running time trial. METHODS: A
      total of 17 male well trained college runners (mean (SD) O(2)MAX 61.3 (4.9)
      ml/kg/min) performed a 5 km treadmill run with and without sodium citrate
      ingestion in a random, double blind, crossover design. In the citrate trial,
      subjects consumed 1 litre of solution containing 0.5 g of sodium citrate/kg body
      mass two hours before the run. In the placebo trial, the same amount of flavoured
      mineral water was consumed. RESULTS: The time required to complete the run was
      faster in the citrate trial than the placebo trial (1153.2 (74.1) and 1183.8
      (91.4) seconds respectively; p = 0.01). Lower packed cell volume and haemoglobin
      levels were found in venous blood samples taken before and after the run in the
      citrate compared with the placebo trial. Lactate concentration in the blood
      sample taken after the run was higher in the citrate than the placebo trial (11.9
      (3.0) v 9.8 (2.8) mmol/l; p<0.001), and glucose concentration was lower (8.3
      (1.9) v 8.8 (1.7) mmol/l; p = 0.02). CONCLUSION: The ingestion of 0.5 g of sodium
      citrate/kg body mass shortly before a 5 km running time trial improves
      performance in well trained college runners.

PMID- 14665585
TI  - Onset of puberty, menstrual frequency, and body fat in elite rhythmic gymnasts
      compared with normal controls.
AB  - OBJECTIVES: To assess the prevalence of delayed menarche and abnormal menstrual
      patterns, as well as the association of menstrual status with physical training
      in elite rhythmic gymnasts from Greece and Canada. METHODS: Fifteen Greek (mean
      (SEM) age 14.5 (0.2) years) and 30 Canadian (mean (SEM) age 14.7 (0.4) years)
      rhythmic gymnasts were surveyed for age at menarche, menstrual frequency, and
      training profile, and measured for height, weight, and percentage body fat (%BF).
      Seventy eight healthy adolescents served as country specific non-active controls:
      38 Greek non-athletes (mean (SEM) age 14.5 (0.1) years) and 40 Canadian non
      athletes (mean (SEM) 14.2 (0.1) years). RESULTS: Of the Greek gymnasts, 79% had
      not yet menstruated compared with 34% of the Canadian gymnasts. Menarche was
      significantly (p<0.01) delayed in the rhythmic gymnasts (composite mean 13.8
      (0.3) years, n = 45) compared with the controls (composite mean 12.5 (0.1) years,
      n = 78). There was no significant difference between Greek and Canadian gymnasts
      for the age at menarche (14.2 (0.3) v 13.6 (1.2) years respectively). Menstrual
      irregularities were reported in 78% (61% oligomenorrhoeic and 17% amenorrhoeic)
      of the menarcheal athletes. Menarcheal gymnasts were found to be significantly
      (p<0.05) taller and heavier, with a higher %BF and a lower training frequency and
      training duration (p<0.05) than the premenarcheal gymnasts. Overall, the mean %BF
      of the gymnasts was significantly lower (p<0.05) than that of the control
      subjects. The Canadian controls exhibited a significantly (p<0.05) greater %BF
      than the Greek controls of the same age. CONCLUSION: Delayed menarche, menstrual
      irregularities, and low body fat are common in elite rhythmic gymnasts.
      Premenarcheal gymnasts train more often and for longer, and have a lower body
      mass index and less body fat, than menarcheal gymnasts. Prospective studies are
      needed to explore further these and other factors associated with delayed
      menarche and menstrual irregularities in female athletes.

PMID- 14665586
TI  - Dynamic force distribution during level walking under the feet of patients with
      chronic ankle instability.
AB  - OBJECTIVES: To examine changes in the pattern of force transfer between the foot
      and the floor associated with chronically sprained ankles by measuring the peak
      forces and their timing under several regions of the feet during level walking.
      METHODS: Twelve young male subjects (mean (SD) age 21 (2) years) with recurrent
      ankle sprains were studied. Seven of them had unilateral and bilateral chronic
      instability and laxity, and five had bilateral instability. Twelve healthy men
      (without orthopaedic or medical disease) served as a control group. Subjects
      walked at their own pace along a 7 m walkway, which included a Mini-EMED pressure
      distribution measuring system. The variables measured were relative peak force
      (fraction of body weight) and relative timing (fraction of stance time). These
      variables were measured under six regions of interest in each foot print: heel,
      midfoot, medial, central, and lateral forefoot, and toes. RESULTS: (a) A
      significant delay to the time of peak force under the central and lateral
      forefoot and toes in subjects with chronic ankle instability. (b) A significant
      decrease in the relative forces under the heel and toes and an increase in the
      relative forces under the midfoot and lateral forefoot in subjects with chronic
      ankle instability. (c) In the patients with unilateral instability, there were no
      significant differences in any of the variables between the injured and non
      injured foot. CONCLUSIONS: In patients with chronic ankle instability, there is a
      slowing down of weight transfer from heel strike to toe off, a reduced impact at
      the beginning and end of the stance phase, and a lateral shift of body weight.

PMID- 14665587
TI  - Severe soccer injuries in amateurs.
AB  - OBJECTIVES: To ascertain the number and type of severe soccer injuries admitted
      to King Edward Hospital in South Africa over 42 months. METHODS: This was a
      retrospective study of all patients admitted for treatment or observation to the
      orthopaedic unit only. Patients treated as outpatients, irrespective of severity,
      are also presented for comparison. RESULTS: Thirty two patients were admitted
      with severe injuries. The injuries included 18 fractures of the tibial and
      femoral shaft. Two tibial shaft fractures were compound. Four tibial plateau
      fractures and five epiphyseal injuries were identified. One patient had a
      fracture-dislocation of the hip. One patient with a popliteal artery injury
      presented 48 hours after the injury had occurred. He had an above knee
      amputation. In the same period 122 patients were treated as outpatients. The
      types of injury in this group were similar to soccer injuries reported in other
      countries. CONCLUSIONS: Very serious injuries are sustained by casual soccer
      players in South Africa. Urgent measures need to be taken to prevent such
      injuries.

PMID- 14665588
TI  - Dehydration of football referees during a match.
AB  - OBJECTIVES: To study hydration status in referees (main) and assistant referees
      (linesmen) during official football matches. METHODS: Twelve male football
      referees were evaluated; all were volunteers. Before and after each match, the
      referee and one of the assistants were weighed without clothes and a blood sample
      was taken. Total water loss was determined for each subject from the change in
      body weight. The main haematological variables were analysed in the blood
      samples. Total plasma protein concentration and osmolarity were also determined.
      Variation in plasma volume was determined from changes in packed cell volume and
      a combination of changes in packed cell volume and haemoglobin concentrations.
      RESULTS: During a match, total body water loss was 1.60 (0.13) litres, equivalent
      to 2.05 (0.18)% of body weight. Body weight was reduced by 1.55 (0.12)%, showing
      that water ingestion during the interval replaces only 24.4% of the body fluids
      lost during the match. The assistants lost 0.79 (0.19) litre of water, equivalent
      to 1.05 (0.25)% of body weight. The referees showed a significant decrease in
      plasma volume of 4.99 (1.33)%. The assistants showed a non-significant increase
      in plasma volume. The reduction in plasma volume observed in the referees
      correlated significantly with total body water loss (r = 0.9623). From these
      data, it is possible to predict that a dehydration of 1% reflects a reduction in
      plasma volume of nearly 2.5%. CONCLUSIONS: Referees are moderately dehydrated
      after a football match (2%), whereas assistants show a non-significant
      dehydration of 1% of their body weight.

PMID- 14665589
TI  - Comprehensive isokinetic knee measurements and quadriceps tendon evaluations in
      footballers for assessing functional performance.
AB  - OBJECTIVES: To ascertain whether detailed isokinetic knee muscle testing reflects
      the results of other functional measurements in footballers and to look for any
      correlations between quadriceps tendon thickness and knee strength. METHODS:
      Ultrasonographic evaluation of the quadriceps tendon (Hitachi EUB-405),
      isokinetic knee testing (Biodex System 3), and sprint measurements using
      telemetric photoelectric cells (Chronometre Prosport ESC TX02) were carried out
      on 29 elite footballers. Jumping capacity was evaluated using Bosco's jumping mat
      (Ergojump). Anaerobic fitness was assessed by auricular capillary blood lactate
      measurements (YSI Model 1500 Sport Lactate Analyzer). RESULTS: Quadriceps tendon
      thickness correlated positively with jumping and sprint measurements and
      negatively with extensor and flexor strength. However, these correlations did not
      reach statistical significance. There were significant correlations between knee
      extensor strength at 60 degrees /s and jumping or sprint measurements and between
      the extension acceleration values of both knees during isokinetic tests at 240
      degrees /s and the sprint measurements. No significant correlation was found
      between the fatigue ratio values of both knees at 240 degrees /s and the
      calculated fatigue ratios from the sprint measurements. CONCLUSIONS: Apart from a
      few variables which correlated with the performance tests, the isokinetic studies
      did not fully predict the various functional measurements. Neither was there any
      relation between the quadriceps tendon measurements and the knee strength values
      nor with the functional performance.

PMID- 14665590
TI  - Snowblading injuries in Eastern Canada.
AB  - OBJECTIVES: To evaluate injury patterns of snowbladers and compare them with
      those of skiers and snowboarders. To determine possible effects of helmet use in
      these sports on injury to the head and neck. METHODS: This prospective case
      series observational study was conducted by collecting the injury reports from
      the ski patrol during the 1999-2000 season at Mont Tremblant ski resort, Quebec.
      All participants in downhill winter sports who presented themselves to the ski
      patrol with traumatic injury related to their sport were included. A concussion
      was defined as any loss of consciousness, amnesia, confusion, disorientation,
      vertigo, or headache that resulted from injury. The ski patroller reported helmet
      use on the accident report at the time of injury. RESULTS: Snowbladers present
      with a unique pattern of injury compared with skiers and snowboarders. The
      incidence of leg, knee, and ankle/foot injuries were 20.5%, 25.6%, and 10.3%
      respectively. Concussions represented 11% of all injuries. There was no increase
      in other injury, including neck injury, related to helmet use. CONCLUSIONS:
      Unique injury patterns in snowbladers warrant reconsideration of equipment
      design. Concussion is a common injury on the ski slope. Although the effects of
      helmet use on concussion rate are inconclusive based on this study, helmet use
      did not increase the rate of neck injury, even when adjusted for age.

PMID- 14665591
TI  - Effect of hyperbaric oxygen on oxygen uptake and measurements in the blood and
      tissues in a normobaric environment.
AB  - OBJECTIVE: To examine venous partial pressure of oxygen (PvO(2)), transcutaneous
      oxygen tension (tcPO(2)), and VO(2)MAX in a normobaric environment after a single
      hyperbaric oxygen (HBO(2)) treatment. METHODS: This was a prospective study of
      conditions after the intervention compared with baseline. The participants were
      10 moderately trained (VO(2)MAX = 57.6 ml/kg/min) men. Two HBO(2) treatments
      consisting of breathing 95% oxygen at 2.5 atmospheres absolute (ATA) for 90
      minutes were administered on non-consecutive days. Baseline testing included
      measures of VO(2)MAX, tcPO(2), and anthropometry. At 6.0 (1.0) minutes after the
      first HBO(2) treatment, a VO(2)MAX test was performed. After the second HBO(2)
      treatment, leg and chest tcPO(2) and PvO(2) were monitored for 60 minutes.
      RESULTS: VO(2)MAX, running time, and peak blood lactate were not altered after
      the HBO(2) treatment. Leg tcPO(2) was lower (p = 0.003) and chest tcPO(2) was
      unchanged after the HBO(2) treatment compared with baseline values. PvO(2) was
      significantly (p<0.001) lower in the first three minutes after treatment than
      subsequent values, but no other differences were found. CONCLUSIONS: A single
      HBO(2) treatment at 2.5 ATA for 90 minutes does not raise PvO(2), tcPO(2), or
      VO(2)MAX in a normobaric, normoxic environment.

PMID- 14665592
TI  - Effects of physical activity on exercise tests and respiratory function.
AB  - BACKGROUND: Exercise is an important component of pulmonary rehabilitation for
      patients with chronic lung disease. OBJECTIVE: To explore the role of physical
      activity in maintaining cardiac and respiratory function in healthy people.
      METHODS: Cardiorespiratory fitness was measured by a maximal treadmill test
      (MTT), and respiratory function was tested by spirometry. The cross sectional
      study included data from 24 536 healthy persons who were examined at the Cooper
      Clinic between 1971 and 1995; the longitudinal study included data from 5707
      healthy persons who had an initial visit between 1971 and 1995 and a subsequent
      visit during the next five years. All participants were aged 25-55 years and
      completed a cardiorespiratory test and a medical questionnaire. RESULTS: In the
      cross sectional study, after controlling for covariates, being active and not
      being a recent smoker were associated with better cardiorespiratory fitness and
      respiratory function in both men and women. In the follow up study, persons who
      remained or became active had better MTT than persons who remained or became
      sedentary. Men who remained active had higher forced expiratory volume in one
      second (FEV(1)) and forced vital capacity (FVC) than the other groups. Smoking
      was related to lower cardiorespiratory fitness and respiratory function.
      CONCLUSIONS: Physical activity and non-smoking or smoking cessation is associated
      with maintenance of cardiorespiratory fitness. Change in physical activity habits
      is associated with change in cardiorespiratory fitness, but respiratory function
      contributed little to this association during a five year follow up.

PMID- 14665593
TI  - Short term effect of feedback on fitness and health measurements on self reported
      appraisal of the stage of change.
AB  - BACKGROUND: An individual's current status of physical activity and nutrition and
      readiness to change can be determined using PACE assessment forms. Practitioners
      have suggested that feedback on the fitness and health components can produce a
      change in a subject's awareness of their behaviour and thereby lead to a
      beneficial change in stage of behaviour change. OBJECTIVE: To evaluate the short
      term effect of personalised feedback on fitness and health status on self
      reported appraisal of the stage of change. METHODS: A total of 299 civil servants
      were randomised to an intervention or a reference group. After having been tested
      for fitness and health, the intervention group received immediate feedback on
      their test results, whereas the reference group did not. PACE assessment forms
      were completed twice: before testing and after testing (reference group), or
      after testing and feedback (intervention group). The time interval between was
      one hour. The influence of feedback was determined using a x(2) test and analysis
      of variance. RESULTS: On the basis of the x(2) test, no significant effect of
      feedback was found on the stage of change of physical activity, nor on the stage
      of change with regard to nutrition. Analysis of variance results showed no
      significant effect on the raw PACE score as to physical activity, intake of fruit
      and vegetables and dietary fat. However, a significant effect was observed on the
      PACE score of "calorie intake and weight management". Subjects in the
      intervention group significantly more often regressed on their PACE score on this
      topic than the reference subjects. CONCLUSIONS: Feedback at baseline on
      measurements of an intervention study can influence PACE scores and can be
      considered as a small but relevant start of the intervention itself.

PMID- 14665594
TI  - Water and land based rehabilitation for Achilles tendinopathy in an elite female
      runner.

PMID- 14665595
TI  - Surfer wipe out by predator fish.
AB  - Needlefish injuries, commonly reported in the Indo-Pacific region, have not been
      previously reported along the European coastlines. This case report describes a
      penetrating injury to the heel of a professional surfer during competition off
      the Portuguese coast. Diagnostic as well as therapeutic recommendations are made.

PMID- 14665596
TI  - Two cases of suprascapular neuropathy in a family.
AB  - Suprascapular entrapment neuropathy is well known in certain athletes, especially
      volleyball players. A brother and sister presented with right shoulder pain and
      wasting of the scapular muscles, particularly the infraspinatus. They had played
      volleyball for over six years and were forced to retire because of disability.
      Investigations showed involvement of the rhomboid muscles also, suggesting a
      probable extension of this syndrome to other nerves in the region such as the
      dorsal scapular nerve.

PMID- 14665597
TI  - Saphenous nerve injury after fasciotomy for compartment syndrome.

PMID- 14665598
TI  - Whole body muscle hypertrophy from resistance training: distribution and total
      mass.
AB  - OBJECTIVE: To examine the absolute and relative changes in skeletal muscle (SM)
      size using whole body magnetic resonance imaging (MRI) in response to heavy
      resistance training (RT). METHOD: Three young men trained three days a week for
      16 weeks. RESULTS: MRI measured total SM mass and fat free mass (FFM) had
      increased by 4.2 kg and 2.6 kg respectively after resistance training.
      CONCLUSIONS: RT induces larger increases in SM mass than in FFM. RT induced
      muscle hypertrophy does not occur uniformly throughout each individual muscle or
      region of the body. Therefore the distribution of muscle hypertrophy and total SM
      mass are important for evaluating the effects of total body RT on muscle size.

PMID- 14665599
TI  - How valid is a self reported 12 month sports injury history?
AB  - BACKGROUND: A past injury history is one of the most commonly cited risk factors
      for sports injury. Often, injury history data are collected by self report
      surveys, with the potential for recall bias. OBJECTIVE: To assess the accuracy of
      a 12 month injury history recall in a population of 70 community level Australian
      football players. METHODS: The retrospective, self reported injury histories of
      70 community level Australian football players were compared with prospective
      injury surveillance records for the same 12 month period. The accuracy of the
      players' recall of the number of injuries, injured body regions, and injury
      diagnosis was assessed. RESULTS: Recall accuracy declined as the level of detail
      requested increased. All players could recall whether or not they were injured
      during the previous year. Almost 80% were able to accurately recall the number of
      injuries and body regions injured, but not the diagnoses, whereas only 61% were
      able to record the exact number, body region, and diagnosis of each injury
      sustained. DISCUSSION: The findings of this study highlight the difficulty of
      using retrospectively collected injury data for research purposes. Any injury
      research relying on self reported injury history data to establish the relation
      between injury history and injury risk should consider the validity of the self
      report injury histories.

PMID- 14665600
TI  - Physiology of accidental hypothermia in the mountains: a forgotten story.
AB  - Hypothermia is a serious condition, often with fatal consequences. The physiology
      and mechanisms of hypothermia in mountainous areas are discussed. It is as
      important to facilitate heat loss, especially during periods of high exertion, as
      it is to maintain heat production and preserve insulation. This can be partly
      achieved by clothing adjustments.

PMID- 14665601
TI  - Reliability of heart rate variability measures at rest and during light exercise
      in children.
AB  - OBJECTIVES: To investigate the reliability of heart rate variability (HRV)
      measures at rest and during light exercise in children. METHODS: Short term (five
      minute) HRV was assessed in 12 children (11-12 years of age). HRV measures were
      collected at rest with the children supine, breathing at 12 breaths/min, and
      during exercise on a cycle ergometer while exercising at 25% of peak oxygen
      uptake. Both resting and exercise data were collected twice from each child.
      RESULTS: Intraclass correlation coefficients were low to moderate for most
      measures with wide confidence intervals for each variable in both resting and
      exercise conditions. Random variation (typical error) within repeated
      measurements ranged from 31% to 187%. CONCLUSIONS: These preliminary findings
      suggest that HRV measures are unreliable at rest and during light exercise in
      children aged 11-12 years. Tighter control of extraneous influences is
      recommended.

PMID- 14665602
TI  - East African running dominance revisited: a role for stereotype threat?
AB  - Regardless of the possible existence of physiological advantages in East African
      runners, belief that such differences exist creates a psychological atmosphere
      that can have significant consequences on performance. This is known as
      stereotype threat and can feature in many sports.

PMID- 14665603
TI  - Psychometric issues associated with computerised neuropsychological assessment of
      concussed athletes.
AB  - Psychometric issues associated with computerised neuropsychological assessment in
      sports concussion are put forward. Issues critical to ensuring test reliability
      and sensitivity are discussed, with particular reference to how inappropriate
      test design can affect clinical decision making.

PMID- 14665604
TI  - An amateur badminton player with juvenile dermatomyositis: courage and questions.

PMID- 14665605
TI  - Silence on clinical fundamentals.

PMID- 14665606
TI  - Sports trainers have accurate but incomplete recall of injury details.

PMID- 14665607
TI  - Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus
      MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized,
      phase III study from the Hellenic Cooperative Oncology Group.
AB  - PURPOSE: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin
      (MVAC) represents the standard regimen for inoperable or metastatic urothelial
      cancer, but its toxicity is significant. We previously reported a 52% response
      rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this
      regimen compared favorably with that reported for MVAC. We thus designed a
      randomized phase III trial to compare DC with MVAC. PATIENTS AND METHODS:
      Patients with inoperable or metastatic urothelial carcinoma; adequate bone
      marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology
      Group performance status < or = 2 were randomly assigned to receive MVAC at
      standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks.
      All patients received prophylactic granulocyte colony-stimulating factor (G-CSF)
      support. RESULT: Two hundred twenty patients were randomly assigned (MVAC, 109
      patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v
      37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and
      median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic
      factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P
      =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31;
      P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P
      =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v
      3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously
      reported for MVAC administered without G-CSF. CONCLUSION: MVAC is more effective
      than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and
      could be used instead of classic MVAC as first-line treatment in advanced
      urothelial carcinoma.

PMID- 14665608
TI  - Phase I trial using a time-to-event continual reassessment strategy for dose
      escalation of cisplatin combined with gemcitabine and radiation therapy in
      pancreatic cancer.
AB  - PURPOSE: The primary objective of this study was to determine the maximum
      tolerated dose of cisplatin that could be added to full-dose gemcitabine and
      radiation therapy (RT) in patients with pancreatic cancer. PATIENTS AND METHODS:
      Nineteen patients were treated. Gemcitabine 1,000 mg/m(2) was administered over
      30 minutes on days 1, 8, and 15 of a 28-day cycle. Cisplatin followed gemcitabine
      on days 1 and 15. The initial dose level of cisplatin was 30 mg/m(2), escalated
      to a targeted dose of 50 mg/m(2) using Time-to-Event Continual Reassessment
      Method. RT was initiated on cycle 1, day 1, in 2.4 Gy fractions to a total dose
      of 36 Gy. A second cycle of chemotherapy was planned following a 1-week rest.
      RESULTS: Four of eight patients experienced acute dose limiting toxicity at the
      50 mg/m(2) cisplatin dose level. Patients treated at 30 and 40 mg/m(2) cisplatin
      dose level tolerated therapy without dose-limiting toxicity. Median survival was
      10.7 months (95% CI, 5.4 to 18.2) for all patients, and 12.9 months (95% CI, 7.4
      to 21.2) for those without metastasis. CONCLUSION: Cisplatin at doses up to 40
      mg/m(2) may be safely added to full-dose gemcitabine and conformal RT. The Time
      to-Event Continual Reassessment Method trial design allowed rapid completion of
      the study and confidence in the conclusion about the maximum tolerated dose, but
      accrued more patients to a dose level above the maximum tolerated dose than the
      typical phase I design. Local and systemic disease control and survival in this
      study cohort supports further investigation of gemcitabine-based RT and
      combination chemotherapy in this disease.

PMID- 14665609
TI  - Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom
      Coordinating Committee on Cancer Research randomized study of adjuvant low-dose
      extended-duration interferon Alfa-2a in high-risk resected malignant melanoma.
AB  - PURPOSE: To evaluate low-dose extended duration interferon alfa-2a as adjuvant
      therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or
      locoregional metastases. PATIENTS AND METHODS: In this randomized controlled
      trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three
      times per week for 2 years or until recurrence) on overall survival (OS) and
      recurrence-free survival (RFS) was compared with that of no further treatment in
      radically resected stage IIB and stage III cutaneous malignant melanoma. RESULTS:
      The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1),
      respectively. There was no significant difference in OS or RFS between the
      interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18;
      P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P
      =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were
      statistically significant adverse features for OS. Subgroup analysis by disease
      stage, age, and sex did not show any clear differences between interferon-treated
      and control groups in either OS or RFS. Interferon-related toxicities were
      modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was
      seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals
      (15%) from interferon treatment due to toxicity. CONCLUSION: The results from
      this study, taken in isolation, do not indicate that extended-duration low-dose
      interferon is significantly better than observation alone in the initial
      treatment of completely resected high-risk malignant melanoma.

PMID- 14665610
TI  - Cost-utility analysis of preoperative radiotherapy in patients with rectal cancer
      undergoing total mesorectal excision: a study of the Dutch Colorectal Cancer
      Group.
AB  - PURPOSE: To compare the societal costs and the (quality-adjusted) life expectancy
      of patients with rectal cancer undergoing total mesorectal excision (TME) with or
      without short-term preoperative radiotherapy (5 x 5 Gy). PATIENTS AND METHODS: We
      used a Markov model to project the clinical and economic outcomes of preoperative
      radiotherapy. Data on local recurrence rates, quality of life, and costs were
      obtained from the patients of a multicenter randomized clinical trial. In this
      trial, 1,861 patients with resectable rectal cancer from 108 hospitals were
      randomly assigned for TME surgery with or without preoperative radiotherapy.
      Outcome measures of the model were life expectancy, quality-adjusted life
      expectancy, lifetime costs per patient, and the incremental cost-effectiveness
      ratio. RESULTS: The base case model estimates that the loss of quality of life
      due to preoperative radiotherapy is outweighed by the gain in life expectancy.
      Life expectancy increases by 0.67 years; quality-adjusted life expectancy, by
      0.39 years; and costs, by $9,800 per patient. The corresponding cost
      effectiveness ratio is $25,100 per quality-adjusted life year. Sensitivity
      analyses indicate that the cost-effectiveness ratio remains acceptable under a
      wide range of assumptions. CONCLUSION: Assuming that the reduced local recurrence
      rate does lead to a survival advantage, the cost-utility analysis estimates that
      the improved survival outweighs the impaired quality of life and the increased
      costs. We conclude that short-term preoperative radiotherapy in patients with
      rectal cancer undergoing TME is both effective and cost-effective.

PMID- 14665611
TI  - A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and
      oxaliplatin combinations in patients with previously untreated metastatic
      colorectal cancer.
AB  - PURPOSE: Three agents with differing mechanisms of action are available for
      treatment of advanced colorectal cancer: fluorouracil, irinotecan, and
      oxaliplatin. In this study, we compared the activity and toxicity of three
      different two-drug combinations in patients with metastatic colorectal cancer who
      had not been treated previously for advanced disease. PATIENTS AND METHODS:
      Patients were concurrently randomly assigned to receive irinotecan and bolus
      fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused
      fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The
      primary end point was time to progression, with secondary end points of response
      rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly
      assigned between May 1999 and April 2001. A median time to progression of 8.7
      months, response rate of 45%, and median survival time of 19.5 months were
      observed for FOLFOX. These results were significantly superior to those observed
      for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or
      for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression
      and response. The FOLFOX regimen had significantly lower rates of severe nausea,
      vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and
      neutropenia were more common with the regimens containing oxaliplatin.
      CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus
      leucovorin was active and comparatively safe. It should be considered as a
      standard therapy for patients with advanced colorectal cancer.

PMID- 14665612
TI  - Adjuvant interferon therapy for melanoma: high-dose, low-dose, no dose, which
      dose?

PMID- 14665613
TI  - Present status and future prospects for adjuvant therapy of melanoma: time to
      build upon the foundation of high-dose interferon alfa-2b.

PMID- 14665614
TI  - The phase III candidate: can we improve the science of selection?

PMID- 14665615
TI  - Phase I's, photons, and philosophies: new tactics for exploratory clinical trials
      of concurrent chemoradiation.

PMID- 14665616
TI  - Economics of preoperative radiotherapy with total mesorectal excision: what can
      we learn from the Dutch experience?

PMID- 14665617
TI  - Scheduling of fluorouracil: a forget-me-not in the jungle of doublets.

PMID- 14665618
TI  - A superfamily of voltage-gated sodium channels in bacteria.
AB  - NaChBac, a six-alpha-helical transmembrane-spanning protein cloned from Bacillus
      halodurans, is the first functionally characterized bacterial voltage-gated Na(+)
      selective channel. As a highly expressing ion channel protein, NaChBac is an
      ideal candidate for high resolution structural determination and structure
      function studies. The biological role of NaChBac, however, is still unknown. In
      this report, another 11 structurally related bacterial proteins are described.
      Two of these functionally expressed as voltage-dependent Na(+) channels (Na(V)PZ
      from Paracoccus zeaxanthinifaciens and Na(V)SP from Silicibacter pomeroyi).
      Na(V)PZ and Na(V)SP share approximately 40% amino acid sequence identity with
      NaChBac. When expressed in mammalian cell lines, both Na(V)PZ and Na(V)SP were
      Na(+)-selective and voltage-dependent. However, their kinetics and voltage
      dependence differ significantly. These single six-alpha-helical transmembrane
      spanning subunits constitute a widely distributed superfamily (Na(V)Bac) of
      channels in bacteria, implying a fundamental prokaryotic function. The degree of
      sequence homology (22-54%) is optimal for future comparisons of Na(V)Bac
      structure and function of similarity and dissimilarity among Na(V)Bac proteins.
      Thus, the Na(V)Bac superfamily is fertile ground for crystallographic,
      electrophysiological, and microbiological studies.

PMID- 14665619
TI  - Photo-oxidative stress in a xanthophyll-deficient mutant of Chlamydomonas.
AB  - When there is an imbalance between the light energy absorbed by a photosynthetic
      organism and that which can be utilized in photosynthesis, photo-oxidative stress
      can damage pigments, proteins, lipids, and nucleic acids. In this work we
      compared the wild type and a xanthophyll-deficient mutant of Chlamydomonas
      reinhardtii in their response to high amounts of light. Wild-type Chlamydomonas
      cells were able to acclimate to high amounts of light following transfer from low
      light conditions. In contrast, the npq1 lor1 double mutant, which lacks
      protective xanthophylls (zeaxanthin and lutein) in the chloroplast, progressively
      lost viability and photosynthetic capacity along with destruction of thylakoid
      membrane protein-pigment complexes and accumulation of reactive oxygen species
      and membrane lipid peroxides. Loss of viability was partially rescued by lowered
      oxygen tension, suggesting that the high sensitivity of the mutant to light
      stress is caused by the production of reactive oxygen species in the chloroplast.
      Cell death was not prevented by the addition of an organic carbon source to the
      growth medium, demonstrating that the photo-oxidative damage can target other
      essential chloroplast processes besides photosynthesis. From the differential
      sensitivity of the mutant to exogenously added pro-oxidants, we infer that the
      reactive oxygen species produced during light stress in npq1 lor1 may be singlet
      oxygen and/or superoxide but not hydrogen peroxide. The bleaching phenotype of
      npq1 lor1 was not due to enhanced photodamage to photosystem II but rather to a
      less localized phenomenon of accumulation of photo-oxidation products in
      chloroplast membranes.

PMID- 14665620
TI  - Identification and characterization of a critical region in the glycogen synthase
      from Escherichia coli.
AB  - The cysteine-specific reagent 5,5'-dithiobis(2-nitrobenzoic acid) inactivates the
      Escherichia coli glycogen synthase (Holmes, E., and Preiss, J. (1982) Arch.
      Biochem. Biophys. 216, 736-740). To find the responsible residue, all cysteines,
      Cys(7), Cys(379), and Cys(408), were substituted combinatorially by Ser. 5,5'
      Dithiobis(2-nitrobenzoic acid) modified and inactivated the enzyme if and only if
      Cys(379) was present and it was prevented by the substrate ADP-glucose (ADP-Glc).
      Mutations C379S and C379A increased the S(0.5) for ADP-Glc 40- and 77-fold,
      whereas the specific activity was decreased 5.8- and 4.3-fold, respectively.
      Studies of inhibition by glucose 1-phosphate and AMP indicated that Cys(379) was
      involved in the interaction of the enzyme with the phosphoglucose moiety of ADP
      Glc. Other mutations, C379T, C379D, and C379L, indicated that this site is
      intolerant for bulkier side chains. Because Cys(379) is in a conserved region,
      other residues were scanned by mutagenesis. Replacement of Glu(377) by Ala and
      Gln decreased V(max) more than 10,000-fold without affecting the apparent
      affinity for ADP-Glc and glycogen binding. Mutation of Glu(377) by Asp decreased
      V(max) only 57-fold indicating that the negative charge of Glu(377) is essential
      for catalysis. The activity of the mutation E377C, on an enzyme form without
      other Cys, was chemically restored by carboxymethylation. Other conserved
      residues in the region, Ser(374) and Gln(383), were analyzed by mutagenesis but
      found not essential. Comparison with the crystal structure of other
      glycosyltransferases suggests that this conserved region is a loop that is part
      of the active site. The results of this work indicate that this region is
      critical for catalysis and substrate binding.

PMID- 14665621
TI  - Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation
      in response to epidermal growth factor.
AB  - Epidermal growth factor (EGF) induces paxillin tyrosine dephosphorylation and Src
      activation, but the signaling pathways that mediate these responses were largely
      undefined. We found that Gab1, a docking protein for the SHP2 protein-tyrosine
      phosphatase in EGF-stimulated cells, was associated with paxillin. SHP2
      dephosphorylated paxillin and caused dissociation of Csk, a negative regulator of
      Src, from paxillin but had no effect on paxillin-Src association. A lower level
      of Src Tyr-530 phosphorylation was detected in paxillin-associated Src in EGF
      stimulated cells. Expression of an SHP2 binding defective mutant of Gab1 (Gab1FF)
      or a catalytically inactive mutant of SHP2 (SHP2DN) prevented paxillin tyrosine
      dephosphorylation and Src activation induced by EGF. Importantly, Gab1FF blocked
      paxillin-SHP2 complex formation, Src Tyr-530 dephosphorylation, Erk activation,
      and cell migration induced by EGF. Inhibition of Src tyrosine kinase activity
      abrogated EGF-stimulated Erk activation and cell migration. Together, these
      results reveal that Gab1 recruits SHP2 to dephosphorylate paxillin, leading to
      dissociation of Csk from the paxillin-Src complex and Src activation and that Src
      is an SHP2 effector involved in EGF-stimulated Erk activation and cell migration.

PMID- 14665622
TI  - Co-recycling of MT1-MMP and MT3-MMP through the trans-Golgi network.
      Identification of DKV582 as a recycling signal.
AB  - Members of the membrane-type matrix metalloproteinases (MT-MMPs) have been
      implicated in a wide range of physiological and pathological processes from
      normal development to tumor growth. Tethered on plasma membrane, these enzymes
      are potentially regulated by the trafficking machinery of the cells. Here we
      demonstrate that both MT1-MMP and MT3-MMP are internalized, transported to the
      trans-Golgi network through early endosomes, and recycled back to cell surface in
      60 min in a manner distinct from the one employed by transferrin receptor.
      Interestingly, co-expressed MT1-MMP and MT3-MMP are localized and routed in the
      same vesicles throughout the trafficking process. We further demonstrated that
      the carboxyl-terminal sequence DKV(582) of MT1-MMP is required for its recycling,
      thus defining a novel recycling motif. These results suggest that MT-MMPs may
      coordinate their proteolytic activities through the cellular trafficking
      machinery.

PMID- 14665623
TI  - The catalytic domain of Escherichia coli Lon protease has a unique fold and a Ser
      Lys dyad in the active site.
AB  - ATP-dependent Lon protease degrades specific short-lived regulatory proteins as
      well as defective and abnormal proteins in the cell. The crystal structure of the
      proteolytic domain (P domain) of the Escherichia coli Lon has been solved by
      single-wavelength anomalous dispersion and refined at 1.75-A resolution. The P
      domain was obtained by chymotrypsin digestion of the full-length, proteolytically
      inactive Lon mutant (S679A) or by expression of a recombinant construct encoding
      only this domain. The P domain has a unique fold and assembles into hexameric
      rings that likely mimic the oligomerization state of the holoenzyme. The hexamer
      is dome-shaped, with the six N termini oriented toward the narrower ring surface,
      which is thus identified as the interface with the ATPase domain in full-length
      Lon. The catalytic sites lie in a shallow concavity on the wider distal surface
      of the hexameric ring and are connected to the proximal surface by a narrow axial
      channel with a diameter of approximately 18 A. Within the active site, the
      proximity of Lys(722) to the side chain of the mutated Ala(679) and the absence
      of other potential catalytic side chains establish that Lon employs a Ser(679)
      Lys(722) dyad for catalysis. Alignment of the P domain catalytic pocket with
      those of several Ser-Lys dyad peptide hydrolases provides a model of substrate
      binding, suggesting that polypeptides are oriented in the Lon active site to
      allow nucleophilic attack by the serine hydroxyl on the si-face of the peptide
      bond.

PMID- 14665624
TI  - AtDGK2, a novel diacylglycerol kinase from Arabidopsis thaliana, phosphorylates 1
      stearoyl-2-arachidonoyl-sn-glycerol and 1,2-dioleoyl-sn-glycerol and exhibits
      cold-inducible gene expression.
AB  - Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DAG) to generate
      phosphatidic acid (PA). Both DAG and PA are implicated in signal transduction
      pathways. DGKs have been widely studied in animals, but their analysis in plants
      is fragmentary. Here, we report the cloning and biochemical characterization of
      AtDGK2, encoding DGK from Arabidopsis thaliana. AtDGK2 has a predicted molecular
      mass of 79.4 kDa and, like AtDGK1 previously reported, harbors two copies of a
      phorbol ester/DAG-binding domain in its N-terminal region. AtDGK2 belongs to a
      family of seven DGK genes in A. thaliana. AtDGK3 to AtDGK7 encode approximately
      55-kDa DGKs that lack a typical phorbol ester/DAG-binding domain.
      Phylogenetically, plant DGKs fall into three clusters. Members of all three
      clusters are widely expressed in vascular plants. Recombinant AtDGK2 was
      expressed in Escherichia coli and biochemically characterized. The enzyme
      phosphorylated 1,2-dioleoyl-sn-glycerol to yield PA, exhibiting Michaelis-Menten
      type kinetics. Estimated K(m) and V(max) values were 125 microm for DAG and 0.25
      pmol of PA min(-1) microg(-1), respectively. The enzyme was maximally active at
      pH 7.2. Its activity was Mg(2+)-dependent and affected by the presence of
      detergents, salts, and the DGK inhibitor R59022, but not by Ca(2+). AtDGK2
      exhibited substrate preference for unsaturated DAG analogues (i.e. 1-stearoyl-2
      arachidonoyl-sn-glycerol and 1,2-dioleoyl-sn-glycerol). The AtDGK2 gene is
      expressed in various tissues of the Arabidopsis plant, including leaves, roots,
      and flowers, as shown by Northern blot analysis and promoter-reporter gene
      fusions. We found that AtDGK2 is induced by exposure to low temperature (4
      degrees C), pointing to a role in cold signal transduction.

PMID- 14665625
TI  - A transient N-terminal interaction of SNAP-25 and syntaxin nucleates SNARE
      assembly.
AB  - The SNARE proteins syntaxin, SNAP-25, and synaptobrevin play a central role
      during Ca(2+)-dependent exocytosis at the nerve terminal. Whereas syntaxin and
      SNAP-25 are located in the plasma membrane, synaptobrevin resides in the membrane
      of synaptic vesicles. It is thought that gradual assembly of these proteins into
      a membrane-bridging ternary SNARE complex ultimately leads to membrane fusion.
      According to this model, syntaxin and SNAP-25 constitute an acceptor complex for
      synaptobrevin. In vitro, however, syntaxin and SNAP-25 form a stable complex that
      contains two syntaxin molecules, one of which is occupying and possibly
      obstructing the binding site of synaptobrevin. To elucidate the assembly pathway
      of the synaptic SNAREs, we have now applied a combination of fluorescence and CD
      spectroscopy. We found that SNARE assembly begins with the slow and rate-limiting
      interaction of syntaxin and SNAP-25. Their interaction was prevented by N
      terminal but not by C-terminal truncations, suggesting that for productive
      assembly all three participating helices must come together simultaneously. This
      suggests a complicated nucleation process that might be the reason for the
      observed slow assembly rate. N-terminal truncations of SNAP-25 and syntaxin also
      prevented the formation of the ternary complex, whereas neither N- nor C-terminal
      shortened synaptobrevin helices lost their ability to interact. This suggests
      that binding of synaptobrevin occurs after the establishment of the syntaxin-SNAP
      25 interaction. Moreover, binding of synaptobrevin was inhibited by an excess of
      syntaxin, suggesting that a 1:1 interaction of syntaxin and SNAP-25 serves as the
      on-pathway SNARE assembly intermediate.

PMID- 14665626
TI  - Biochemical investigations of control of replication initiation of plasmid R6K.
AB  - The mechanistic basis of control of replication initiation of plasmid R6K was
      investigated by addressing the following questions. What are the biochemical
      attributes of mutations in the pi initiator protein that caused loss of negative
      control of initiation? Did the primary control involve only initiator protein-ori
      DNA interaction or did it also involve protein-protein interactions between pi
      and several host-encoded proteins? Mutations at two different regions of the pi
      encoding sequence individually caused some loss of negative control as indicated
      by a relatively modest increase in copy number. However, combinations of the
      mutation P42L, which caused loss of DNA looping, with those located in the region
      between the residues 106 and 113 induced a robust enhancement of copy number.
      These mutant forms promoted higher levels of replication in vitro in a
      reconstituted system consisting of 22 purified proteins. The mutant forms of pi
      were susceptible to pronounced iteron-induced monomerization in comparison with
      the WT protein. As contrasted with the changes in DNA-protein interaction, we
      found no detectable differences in protein-protein interaction between wild type
      pi with DnaA, DnaB helicase, and DnaG primase on one hand and between the high
      copy mutant forms and the same host proteins on the other. The DnaG-pi
      interaction reported here is novel. Taken together, the results suggest that both
      loss of negative control due to iteron-induced monomerization of the initiator
      and enhanced iteron-initiator interaction appear to be the principal causes of
      enhanced copy number.

PMID- 14665627
TI  - Evidence for radical formation at Tyr-353 in Mycobacterium tuberculosis catalase
      peroxidase (KatG).
AB  - Mycobacterium tuberculosis KatG is a heme-containing catalase-peroxidase
      responsible for activation, through its peroxidase cycle, of the front line
      antituberculosis antibiotic isoniazid (isonicotinic acid hydrazide). Formation of
      Compound I (oxyferryl heme-porphyrin pi-cation radical), the classical peroxidase
      intermediate generated when the resting enzyme turns over with alkyl peroxides,
      is rapidly followed by production of a protein-centered tyrosyl radical in this
      enzyme. In our efforts to identify the residue at which this radical is formed,
      nitric oxide was used as a radical scavenging reagent. Quenching of the tyrosyl
      radical generated in the presence of NO was shown using electron paramagnetic
      resonance spectroscopy, and formation of nitrotyrosine was confirmed by
      proteolytic digestion followed by high performance liquid chromatography analysis
      of the NO-treated enzyme. These results are consistent with formation of
      nitrosyltyrosine by addition of NO to tyrosyl radical and oxidation of this
      intermediate to nitrotyrosine. Two predominant nitrotyrosine-containing peptides
      were identified that were purified and sequenced by Edman degradation. Both
      peptides were derived from the same M. tuberculosis KatG sequence spanning
      residues 346-356 with the amino acid sequence SPAGAWQYTAK, and both peptides
      contained nitrotyrosine at residue 353. Some modification of Trp-351 most
      probably into nitrosotryptophan was also found in one of the two peptides.
      Control experiments using denatured KatG or carried out in the absence of
      peroxide did not produce nitrotyrosine. In the mutant enzyme KatG(Y353F), which
      was constructed using site-directed mutagenesis, a tyrosyl radical was also
      formed upon turnover with peroxide but in poor yield compared with wild-type
      KatG. Residue Tyr-353 is unique to M. tuberculosis KatG and may play a special
      role in the function of this enzyme.

PMID- 14665628
TI  - Definition of the consensus motif recognized by gamma-adaptin ear domains.
AB  - The heterotetrameric adaptor complex 1 (AP-1) and the monomeric Golgi-localized,
      gamma ear-containing, Arf-binding (GGA) proteins are components of clathrin coats
      associated with the trans-Golgi network and endosomes. The carboxyl-terminal ear
      domains (or gamma-adaptin ear (GAE) domains) of two gamma-adaptin subunit
      isoforms of AP-1 and of the GGAs are structurally similar and bind to a common
      set of accessory proteins. In this study, we have systematically defined a core
      tetrapeptide motif PsiG(P/D/E)(Psi/L/M) (where Psi is an aromatic residue), which
      is responsible for the interactions of accessory proteins with GAE domains. The
      definition of this motif has allowed us to identify novel GAE-binding partners
      named NECAP and aftiphilin, which also contain clathrin-binding motifs. These
      findings shed light on the mechanism of accessory protein recruitment to trans
      Golgi network and endosomal clathrin coats.

PMID- 14665629
TI  - Distinct maturations of N-propeptide domains in fibrillar procollagen molecules
      involved in the formation of heterotypic fibrils in adult sea urchin collagenous
      tissues.
AB  - We have characterized the primary structure of a new sea urchin fibrillar
      collagen, the 5alpha chain, including nine repeats of the sea urchin fibrillar
      module in its N-propeptide. By Western blot and immunofluorescence analyses, we
      have shown that 5alpha is co-localized in adult collagenous ligaments with the
      2alpha fibrillar collagen chain and fibrosurfin, two other extracellular matrix
      proteins possessing sea urchin fibrillar modules. At the ultrastructural level,
      the 5alpha N-propeptide is detected at the surface of fibrils, suggesting the
      retention of this domain in mature collagen molecules. Biochemical
      characterization of pepsinized collagen molecules extracted from the test tissue
      (the endoskeleton) together with a matrix-assisted laser desorption ionization
      time-of-flight analysis allowed us to determine that 5alpha is a quantitatively
      minor fibrillar collagen chain in comparison with the 1alpha and 2alpha chains.
      Moreover, 5alpha forms heterotrimeric molecules with two 1alpha chains. Hence, as
      in vertebrates, sea urchin collagen fibrils are made up of quantitatively major
      and minor fibrillar molecules undergoing distinct maturation of their N
      propeptide regions and participating in the formation of heterotypic fibrils.

PMID- 14665630
TI  - Regulation of p53 stability and function in HCT116 colon cancer cells.
AB  - We have used a lentiviral vector to stably express p53 at a physiological level
      in p53 knockout HCT116 cells. Cells transduced with wild type p53 responded to
      genotoxic stress by stabilizing p53 and expressing p53 target genes. The
      reconstituted cells underwent G(1) arrest or apoptosis appropriately depending on
      the type of stress, albeit less efficiently than parental wild type cells.
      Compared with cells expressing exogenous wild type p53, the apoptotic response to
      5-fluorouracil (5FU) was >50% reduced in cells expressing S15A or S20A mutant
      p53, and even more reduced by combined mutation of serines 6, 9, 15, 20, 33, and
      37 (N6A). Among a panel of p53 target genes tested by quantitative PCR, the gene
      showing the largest defect in induction by 5FU was BBC3 (PUMA), which was induced
      4-fold by wild type p53 and 2-fold by the N6A mutant. Mutation of N-terminal
      phosphorylation sites did not prevent p53 stabilization by doxorubicin or 5FU.
      MDM2 silencing by RNA interference activated p53 target gene expression in normal
      fibroblasts but not in HCT116 cells, and exogenous p53 could be stabilized in
      HCT116 knockout cells despite combined mutation of p53 phosphorylation sites and
      silencing of MDM2 expression. The MDM2 feedback loop is thus defective, and other
      mechanisms must exist to regulate p53 stability and function in this widely used
      tumor cell line.

PMID- 14665631
TI  - Dimerization of TonB is not essential for its binding to the outer membrane
      siderophore receptor FhuA of Escherichia coli.
AB  - FhuA belongs to a family of specific siderophore transport systems located in the
      outer membrane of Escherichia coli. The energy required for the transport process
      is provided by the proton motive force of the cytoplasmic membrane and is
      transmitted to FhuA by the protein TonB. Although the structure of full-length
      TonB is not known, the structure of the last 77 residues of a fragment composed
      of the 86 C-terminal amino acids was recently solved and shows an intertwined
      dimer (Chang, C., Mooser, A., Pluckthun, A., and Wlodawer, A. (2001) J. Biol.
      Chem. 276, 27535-27540). We analyzed the ability of truncated C-terminal TonB
      fragments of different lengths (77, 86, 96, 106, 116, and 126 amino acid
      residues, respectively) to bind to the receptor FhuA. Only the shortest TonB
      fragment, TonB-77, could not effectively interact with FhuA. We have also
      observed that the fragments TonB-77 and TonB-86 form homodimers in solution,
      whereas the longer fragments remain monomeric. TonB fragments that bind to FhuA
      in vitro also inhibit ferrichrome uptake via FhuA in vivo and protect cells
      against attack by bacteriophage Phi80.

PMID- 14665632
TI  - Components of a pathway maintaining histone modification and heterochromatin
      protein 1 binding at the pericentric heterochromatin in Mammalian cells.
AB  - Heterochromatin is a higher order chromatin structure that is important for
      transcriptional silencing, chromosome segregation, and genome stability. The
      establishment and maintenance of heterochromatin is regulated not only by genetic
      elements but also by epigenetic elements that include histone tail modification
      (e.g. acetylation and methylation) and DNA methylation. Here we show that the
      p33ING1-Sin3-HDAC complex as well as DNA methyltransferase 1 (DNMT1) and DNMT1
      associated protein 1 (DMAP1) are components of a pathway required for maintaining
      proper histone modification and heterochromatin protein 1 binding at the
      pericentric heterochromatin. p33ING1 and DMAP1 interact physically and co
      localize to heterochromatin in the late S phase, and both are required for
      heterochromatin protein 1 binding to heterochromatin. Although the p33ING1-Sin3
      HDAC and DMAP1-DNMT1 complexes are recruited independently to pericentric
      heterochromatin regions, they are both required for deacetylation of histones and
      methylation of histone H3 at lysine 9. These data support a cooperative model for
      histone deacetylation, methylation, and DNA methylation in maintaining
      pericentric heterochromatin structure throughout cell divisions.

PMID- 14665633
TI  - Inhibition of AP-1 and neoplastic transformation by fresh apple peel extract.
AB  - Consumption of fruits and vegetables has been associated with a low incidence of
      cancers and other chronic diseases. Previous studies suggested that fresh apples
      inhibit tumor cell proliferation. Here we report that oral administration of
      apple peel extracts decreased the number of nonmalignant and malignant skin
      tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12
      dimethylbenz(a)anthracene-initiated mouse skin. ESR analysis indicated that apple
      extract strongly scavenged hydroxyl (OH) and superoxide (O(2)(-)) radicals.
      Mechanistic studies showed that pretreatment with apple peel extract inhibited AP
      1 transactivation induced by ultraviolet B irradiation or TPA in JB6 cells and AP
      1-luciferase reporter transgenic mice. This inhibitory effect appears to be
      mediated by the inhibition of ERKs and JNK activity. The results provide the
      first evidence that an extract from fresh apple peel extract may inhibit tumor
      promoter-induced carcinogenesis and associated cell signaling, and suggest that
      the chemopreventive effects of fresh apple may be through its antioxidant
      properties by blocking reactive oxygen species-mediated AP-1-MAPK activation.

PMID- 14665634
TI  - The DNA binding properties of the Escherichia coli RecQ helicase.
AB  - The RecQ helicase family is highly conserved from bacteria to men and plays a
      conserved role in the preservation of genome integrity. Its deficiency in human
      cells leads to a marked genomic instability that is associated with premature
      aging and cancer. To determine the thermodynamic parameters for the interaction
      of Escherichia coli RecQ helicase with DNA, equilibrium binding studies have been
      performed using the thermodynamic rigorous fluorescence titration technique.
      Steady-state fluorescence anisotropy measurements of fluorescein-labeled
      oligonucleotides revealed that RecQ helicase bound to DNA with an apparent
      binding stoichiometry of 1 protein monomer/10 nucleotides. This stoichiometry was
      not altered in the presence of AMPPNP (adenosine 5'-(beta,gamma-imido)
      triphosphate) or ADP. Analyses of RecQ helicase interactions with
      oligonucleotides of different lengths over a wide range of pH, NaCl, and nucleic
      acid concentrations indicate that the RecQ helicase has a single strong DNA
      binding site with an association constant at 25 degrees C of K=6.7 +/- 0.95 x
      10(6) M(-1) and a cooperativity parameter of omega=25.5 +/- 1.2. Both single
      stranded DNA and double-stranded DNA bind competitively to the same site. The
      intrinsic affinities are salt-dependent, and the formation of DNA-helicase
      complex is accompanied by a net release of 3-4 ions. Allosteric effects of
      nucleotide cofactors on RecQ binding to DNA were observed only for single
      stranded DNA in the presence of 1.5 mM AMPPNP, whereas both AMPPNP and ADP had no
      detectable effect on double-stranded DNA binding over a large range of nucleotide
      cofactor concentrations.

PMID- 14665635
TI  - Familial Parkinson's disease-associated L166P mutation disrupts DJ-1 protein
      folding and function.
AB  - Mutations in DJ-1, a protein of unknown function, were recently identified as the
      cause for an autosomal recessive, early onset form of familial Parkinson's
      disease. Here we report that DJ-1 is a dimeric protein that exhibits protease
      activity but no chaperone activity. The protease activity was abolished by
      mutation of Cys-106 to Ala, suggesting that DJ-1 functions as a cysteine
      protease. Our studies revealed that the Parkinson's disease-linked L166P mutation
      impaired the intrinsic folding propensity of DJ-1 protein, resulting in a
      spontaneously unfolded structure that was incapable of forming a homodimer with
      itself or a heterodimer with wild-type DJ-1. Correlating with the disruption of
      DJ-1 structure, the L166P mutation abolished the catalytic function of DJ-1.
      Furthermore, as a result of protein misfolding, the L166P mutant DJ-1 was
      selectively polyubiquitinated and rapidly degraded by the proteasome. Together
      these findings provide insights into the molecular mechanism by which loss-of
      function mutations in DJ-1 lead to Parkinson's disease.

PMID- 14665636
TI  - Functional and physical interaction of the human ARF tumor suppressor with Tat
      binding protein-1.
AB  - The p14ARF tumor suppressor is a key regulator of cellular proliferation,
      frequently inactivated in human cancer, whose mode of action is currently not
      completely understood. We report here that the so-called human immunodeficiency
      virus Tat-binding protein-1 (TBP-1), a component of the 19 S regulatory subunit
      of the proteasome 26 S, also involved in transcriptional regulation and with a
      supposed role in the control of cell proliferation, specifically interacts with
      ARF, both in yeast and mammalian cells. We present evidence that the
      overexpression of TBP-1 in various cell lines results in a sharp increase of both
      transfected and endogenous ARF protein levels. Moreover, this effect depends on
      the binding between the two proteins and, at least in part, is exerted at the
      post-translational level. We also show that the ARF increase following TBP-1
      overexpression results in an increase in p53 protein levels and activity.
      Finally, our data underline a clear involvement of TBP-1 in the control of cell
      proliferation.

PMID- 14665637
TI  - The rapid effects of 1,25-dihydroxyvitamin D3 require the vitamin D receptor and
      influence 24-hydroxylase activity: studies in human skin fibroblasts bearing
      vitamin D receptor mutations.
AB  - If both rapid and genomic pathways may co-exist in the same cell, the involvement
      of the nuclear vitamin D receptor (VDR) in the rapid effects of 1,25
      dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) remains unclear. We therefore studied
      rapid and long term effects of 1,25-(OH)(2)D(3) in cultured skin fibroblasts from
      three patients with severe vitamin D-resistant rickets and one age-matched
      control. Patients bear homozygous missense VDR mutations that abolished either
      VDR binding to DNA (patient 1, mutation K45E) or its stable ligand binding
      (patients 2 and 3, mutation W286R). In patient 1 cells, 1,25-(OH)(2)D(3) (1 pm-10
      nm) had no effect on either intracellular calcium or 24-hydroxylase (enzyme
      activity and mRNA expression). In contrast, cells bearing the W286R mutation had
      calcium responses to 1,25-(OH)(2)D(3) (profile and magnitude) and 24-hydroxylase
      responses to low (1 pm-100 pm) 1,25-(OH)(2)D(3) concentrations (activity, CYP24,
      and ferredoxin mRNAs) similar to those of controls. The blocker of Ca(2+)
      channels, verapamil, impeded both rapid (calcium) and long term (24-hydroxylase
      activity, CYP24, and ferredoxin mRNAs) responses in patient and control
      fibroblasts. The MEK 1/2 kinase inhibitor PD98059 also blocked the CYP24 mRNA
      response. Taken together, these results suggest that 1,25-(OH)(2)D(3) rapid
      effects require the presence of VDR and control, in part, the first step of 1,25
      (OH)(2)D(3) catabolism via increased mRNA expression of the CYP24 and ferredoxin
      genes in the 24-hydroxylase complex.

PMID- 14665638
TI  - Tyrosine residues affecting sodium stimulation of carnitine transport in the
      OCTN2 carnitine/organic cation transporter.
AB  - Primary carnitine deficiency is a disorder of fatty acid oxidation caused by
      mutations in the Na+-dependent carnitine/organic cation transporter OCTN2.
      Studies with tyrosyl group-modifying reagents support the involvement of tyrosine
      residues in Na+ binding by sodium-coupled transporters. Here we report two new
      patients with carnitine deficiency caused by mutations affecting tyrosyl residues
      (Y447C and Y449D) close to a residue (Glu-452) previously shown to affect sodium
      stimulation of carnitine transport. Kinetic analysis indicated that the Y449D
      substitution, when expressed in Chinese hamster ovary cells, increased the
      concentration of sodium required to half-maximally stimulate carnitine transport
      from 14.8 +/- 1.8 to 34.9 +/- 5.8 mM (p<0.05), whereas Y447C completely abolished
      carnitine transport. Substitution of these tyrosine residues with phenylalanine
      restored normal carnitine transport in Y449F but resulted in markedly impaired
      carnitine transport by Y447F. This was associated with an increase in the
      concentration of sodium required to half-maximally stimulate carnitine transport
      to 57.8 +/- 7.4 mM (p<0.01 versus normal OCTN2). The Y447F and Y449D mutant
      transporters retained their ability to transport the organic cation
      tetraethylammonium indicating that their effect on carnitine transport was
      specific and likely associated with the impaired sodium stimulation of carnitine
      transport. By contrast, the Y447C natural mutation abolished the transport of
      organic cations in addition to carnitine. Confocal microscopy of OCTN2
      transporters tagged with green fluorescent protein indicated that the Y447C
      mutant transporters failed to reach the plasma membrane, whereas Y447F, Y449D,
      and Y449F had normal membrane localization. These natural mutations identify
      tyrosine residues possibly involved in coupling the sodium electrochemical
      gradient to transmembrane solute transfer in the sodium-dependent co-transporter
      OCTN2.

PMID- 14665639
TI  - Regulation and biochemistry of mouse molybdo-flavoenzymes. The DBA/2 mouse is
      selectively deficient in the expression of aldehyde oxidase homologues 1 and 2
      and represents a unique source for the purification and characterization of
      aldehyde oxidase.
AB  - Mouse molybdo-flavoenzymes consist of xanthine oxidoreductase, aldehyde oxidase
      (AOX1), and two recently identified proteins, AOH1 and AOH2 (aldehyde oxidase
      homologues 1 and 2). Here we demonstrate that CD-1, C57BL/6, 129/Sv, and other
      mouse strains synthesize high levels of AOH1 in the liver and AOH2 in the skin.
      By contrast, the DBA/2 and CBA strains are unique, having a selective deficit in
      the expression of the AOH1 and AOH2 genes. DBA/2 animals synthesize trace amounts
      of a catalytically active AOH1 protein. However, relative to CD-1 animals, an
      over 2 log reduction in the steady-state levels of liver AOH1 mRNA, protein, and
      enzymatic activity is observed in basal conditions and following administration
      of testosterone. The DBA/2 mouse represents a unique opportunity to purify AOX1
      and compare its enzymatic characteristics to those of the AOH1 protein. The
      spectroscopy and biochemistry of AOX1 are very similar to those of AOH1 except
      for a differential sensitivity to the non-competitive inhibitory effect of
      norharmane. AOX1 and AOH1 oxidize an overlapping set of aldehydes and
      heterocycles. For most compounds, the substrate efficiency (V(max)/K(m)) of AOX1
      is superior to that of AOH1. Alkylic alcohols and acetaldehyde, the toxic
      metabolite of ethanol, are poor substrates of both enzymes. Consistent with this,
      the levels of acetaldehyde in the livers of ethanol administered CD-1 and DBA/2
      mice are similar, indicating that neither enzyme is involved in the in vivo
      biotransformation of acetaldehyde.

PMID- 14665641
TI  - Northern Rx-posure: US, Canada clash on cross-border medication sales.

PMID- 14665640
TI  - Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration
      and sprouting but not survival of endothelial cells.
AB  - Angiopoietin-1 can promote migration, sprouting, and survival of endothelial
      cells through activation of different signaling pathways triggered by the Tie2
      tyrosine kinase receptor. ShcA adapter proteins are targets of activated tyrosine
      kinases and are implicated in the transmission of activation signals to the
      Ras/mitogen-activated protein kinase pathway. Here we report the identification
      of an interaction between the adapter protein ShcA and the cytoplasmic domain of
      Tie2 through in vitro co-immunoprecipitation analysis. Stimulation of endogenous
      Tie2 in endothelial cells with its ligand angiopoietin-1 increased its
      association with ShcA and phosphorylation of the adapter protein. The interaction
      requires the SH2 domain of ShcA and the tyrosine phosphorylation of Tie2 as shown
      by pull-down experiments. Furthermore, Tyr-1101 of Tie2 was identified as the
      primary binding site for the SH2 domain of ShcA. Overexpression of a dominant
      negative form of ShcA affects angiopoietin-1-induced chemotaxis and sprouting,
      although it has no effect on survival of endothelial cells. Furthermore, this
      mutant partially reduces the tyrosine phosphorylation of the regulatory p85
      subunit of phosphatidylinositol 3-kinase. Together, our results identified a
      novel interaction between Tie2 with the adapter molecule ShcA and suggested that
      this interaction may play a role in the regulation of migration and three
      dimensional organization of endothelial cells induced by angiopoietin-1.

PMID- 14665642
TI  - Familial link seen in obstructive sleep apnea.

PMID- 14665647
TI  - Topical antibiotics before cataract surgery.

PMID- 14665648
TI  - Age and sex as independent risk factors for stroke among patients with atrial
      fibrillation.

PMID- 14665649
TI  - End-of-life practices in European intensive care units.

PMID- 14665650
TI  - End-of-life practices in European intensive care units.

PMID- 14665651
TI  - Lifestyle as a factor in medical students' career choices.

PMID- 14665652
TI  - Factors in the increasing prevalence of hypertension.

PMID- 14665653
TI  - Lifestyle as a factor in medical students' career choices.

PMID- 14665654
TI  - Benzodiazepine use and risk of mortality in individuals aged 85 years or older.

PMID- 14665655
TI  - C-reactive protein and the risk of developing hypertension.
AB  - CONTEXT: Although it has been hypothesized that hypertension is in part an
      inflammatory disorder, clinical data linking inflammation with incident
      hypertension are scarce. OBJECTIVE: To examine whether C-reactive protein levels,
      a marker of systemic inflammation, are associated with incident hypertension.
      DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study that began in 1992
      of 20 525 female US health professionals aged 45 years or older who provided
      baseline blood samples with initially normal levels of blood pressure (BP)
      (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of
      hypertension or antihypertensive medications) and then followed up for a median
      of 7.8 years for the development of incident hypertension. Plasma C-reactive
      protein levels were measured and baseline coronary risk factors were collected.
      MAIN OUTCOME MEASURE: Incident hypertension, defined as either a new physician
      diagnosis, the initiation of antihypertensive treatment, or self-reported
      systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg.
      RESULTS: During follow-up, 5365 women developed incident hypertension. In crude
      models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing
      hypertension from the lowest (referent) to the highest levels of baseline C
      reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68),
      1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In
      fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00,
      1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and
      1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was
      significantly associated with an increased risk of developing hypertension in all
      prespecified subgroups evaluated, including those with very low levels of
      baseline BP, as well as those with no traditional coronary risk factors. Similar
      results were found when treating C-reactive protein as a continuous variable and
      controlling for baseline BP. CONCLUSION: C-reactive protein levels are associated
      with future development of hypertension, which suggests that hypertension is in
      part an inflammatory disorder.

PMID- 14665656
TI  - Combined levothyroxine plus liothyronine compared with levothyroxine alone in
      primary hypothyroidism: a randomized controlled trial.
AB  - CONTEXT: Standard therapy for patients with primary hypothyroidism is replacement
      with synthetic thyroxine, which undergoes peripheral conversion to
      triiodothyronine, the active form of thyroid hormone. Within the lay population
      and in some medical communities, there is a perception that adding synthetic
      triiodothyronine, or liothyronine, to levothyroxine improves the symptoms of
      hypothyroidism despite insufficient evidence to support this practice. OBJECTIVE:
      To evaluate the benefits of treating primary hypothyroidism with levothyroxine
      plus liothyronine combination therapy vs levothyroxine monotherapy. DESIGN,
      SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial
      conducted from May 2000 to February 2002 at a military treatment facility that
      serves active duty and retired military personnel and their family members. The
      trial included a total of 46 patients aged 24 to 65 years with at least a 6-month
      history of treatment with levothyroxine for primary hypothyroidism. INTERVENTION:
      Patients received either their usual dose of levothyroxine (n = 23) or
      combination therapy (n = 23), in which their usual levothyroxine dose was reduced
      by 50 micro g/d and substituted with liothyronine, 7.5 micro g, taken twice daily
      for 4 months. MAIN OUTCOME MEASURES: Scores on a hypothyroid-specific health
      related quality-of-life (HRQL) questionnaire, body weight, serum lipid levels,
      and 13 neuropsychological tests measured before and after treatment. RESULTS:
      Serum thyrotropin levels remained similar and within the normal range in both
      treatment groups from baseline to 4 months. Body weight and serum lipid levels
      did not change. The HRQL questionnaire scores improved significantly in both the
      control group (23%; P<.001) and the combination therapy group (12%; P =.02), but
      these changes were statistically similar (P =.54). In 12 of 13 neuropsychological
      tests, outcomes between groups were not significantly different; the 1 remaining
      test (Grooved Peg Board) showed better performance in the control group.
      CONCLUSION: Compared with levothyroxine alone, treatment of primary
      hypothyroidism with combination levothyroxine plus liothyronine demonstrated no
      beneficial changes in body weight, serum lipid levels, hypothyroid symptoms as
      measured by a HRQL questionnaire, and standard measures of cognitive performance.

PMID- 14665657
TI  - Risk factors for advanced colonic neoplasia and hyperplastic polyps in
      asymptomatic individuals.
AB  - CONTEXT: Knowledge of risk factors for colorectal neoplasia could inform risk
      reduction strategies for asymptomatic individuals. Few studies have evaluated
      risk factors for advanced colorectal neoplasia in asymptomatic individuals,
      compared risk factors between persons with and without polyps, or included most
      purported risk factors in a multivariate analysis. OBJECTIVE: To determine risk
      factors associated with advanced colorectal neoplasia in a cohort of asymptomatic
      persons with complete colonoscopy. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective, cross-sectional study of 3121 asymptomatic patients aged 50 to 75
      years from 13 Veterans Affairs medical centers conducted between February 1994
      and January 1997. All participants had complete colonoscopy to determine the
      prevalence of advanced neoplasia, defined as an adenoma that was 10 mm or more in
      diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive
      cancer. Variables examined included history of first-degree relative with
      colorectal cancer, prior cholecystectomy, serum cholesterol level, physical
      activity, smoking, alcohol use, and dietary factors. MAIN OUTCOME MEASURES: An
      age-adjusted analysis was performed for each variable to calculate the odds
      ratios (ORs) and 95% confidence intervals (CIs) associated with having advanced
      neoplasia compared with having no polyps. We developed a multivariate logistic
      regression model to identify the most informative risk factors. A secondary
      analysis examined risk factors for having hyperplastic polyps compared with
      having no polyps and compared with having advanced neoplasia. RESULTS: Three
      hundred twenty-nine participants had advanced neoplasia and 1441 had no polyps.
      In multivariate analyses, we found positive associations for history of a first
      degree relative with colorectal cancer (OR, 1.66; 95% CI, 1.16-2.35), current
      smoking (OR, 1.85; 95% CI, 1.33-2.58), and current moderate to heavy alcohol use
      (OR, 1.02; 95% CI, 1.01-1.03). Inverse associations were found for cereal fiber
      intake (OR, 0.95; 95% CI, 0.91-0.99), vitamin D intake (OR, 0.94; 95% CI, 0.90
      0.99), and use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 0.66; 95%
      CI, 0.48-0.91). In the univariate analysis, the inverse association was found
      with cereal fiber intake greater than 4.2 g/d, vitamin D intake greater than 645
      IU/d, and daily use of NSAIDs. Marginal factors included physical activity, daily
      multivitamin use, and intake of calcium and fat derived from red meat. No
      association was found for body mass index, prior cholecystectomy, or serum
      cholesterol level. Three hundred ninety-one patients had hyperplastic polyps as
      the worst lesion found at colonoscopy. Risk variables were similar to those for
      patients with no polyps, except that past and current smoking were associated
      with an increased risk of hyperplastic polyps. CONCLUSIONS: Our data endorse
      several important risk factors for advanced colonic neoplasia and provide a
      rationale for prudent risk reduction strategies. Further study is needed to
      determine if lifestyle changes can moderate the risk of colorectal cancer.

PMID- 14665658
TI  - Trends in pertussis among infants in the United States, 1980-1999.
AB  - CONTEXT: Reported cases of pertussis among adolescents and adults have increased
      since the 1980s, despite increasingly high rates of vaccination among infants and
      children. However, severe pertussis morbidity and mortality occur primarily among
      infants. OBJECTIVE: To describe the trends and characteristics of reported cases
      of pertussis among infants younger than 12 months in the United States from 1980
      to 1999. DESIGN, SETTING, AND PARTICIPANTS: Cases of pertussis in infants younger
      than 12 months in the United States reported to the National Notifiable Disease
      Surveillance System of the Centers for Disease Control and Prevention between
      1980 and 1999, and detailed case data from the Supplementary Pertussis
      Surveillance System. MAIN OUTCOME MEASURES: Incidence and demographic and
      clinical characteristics of cases. RESULTS: The incidence of reported cases of
      pertussis among infants increased 49% in the 1990s compared with the incidence in
      the 1980s (19 798 vs 12 550 cases reported; 51.1 cases vs 34.2 cases per 100 000
      infant population, respectively). Increases in the incidence of cases and the
      number of deaths among infants during the 1990s primarily were among those aged 4
      months or younger, contrasting with a stable incidence of cases among infants
      aged 5 months or older. The proportion of cases confirmed by bacterial culture
      was higher in the 1990s than in the 1980s (50% and 33%, respectively); the
      proportion of hospitalized cases was unchanged (67% vs 68%, respectively).
      Receipt of fewer doses of vaccine was associated with hospitalization, when cases
      were stratified by age in months. CONCLUSIONS: The incidence of reported cases of
      pertussis among infants increased in the 1990s compared with the 1980s. The
      limited age group affected, the increased rate of bacteriologic confirmation, and
      the unchanged severity of illness suggest that an increase in infant pertussis
      has occurred apart from any change in reporting. Strategies are needed to prevent
      the morbidity and mortality from pertussis among infants too young to be fully
      vaccinated, according to the current recommended schedules of vaccination in the
      United States.

PMID- 14665659
TI  - Comparison of community- and health care-associated methicillin-resistant
      Staphylococcus aureus infection.
AB  - CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally
      been considered a health care-associated pathogen in patients with established
      risk factors. However, MRSA has emerged in patients without established risk
      factors (community-associated MRSA). OBJECTIVE: To characterize epidemiological
      and microbiological characteristics of community-associated MRSA cases compared
      with health care-associated MRSA cases. DESIGN, SETTING, AND PATIENTS:
      Prospective cohort study of patients with MRSA infection identified at 12
      Minnesota laboratory facilities from January 1 through December 31, 2000,
      comparing community-associated (median age, 23 years) with health care-associated
      (median age, 68 years) MRSA cases. MAIN OUTCOME MEASURES: Clinical infections
      associated with either community-associated or health care-associated MRSA,
      microbiological characteristics of the MRSA isolates including susceptibility
      testing, pulsed-field gel electrophoresis, and staphylococcal exotoxin gene
      testing. RESULTS: Of 1100 MRSA infections, 131 (12%) were community-associated
      and 937 (85%) were health care-associated; 32 (3%) could not be classified due to
      lack of information. Skin and soft tissue infections were more common among
      community-associated cases (75%) than among health care-associated cases (37%)
      (odds ratio [OR], 4.25; 95% confidence interval [CI], 2.97-5.90). Although
      community-associated MRSA isolates were more likely to be susceptible to 4
      antimicrobial classes (adjusted OR, 2.44; 95% CI, 1.35-3.86), most community
      associated infections were initially treated with antimicrobials to which the
      isolate was nonsusceptible. Community-associated isolates were also more likely
      to belong to 1 of 2 pulsed-field gel electrophoresis clonal groups in both
      univariate and multivariate analysis. Community-associated isolates typically
      possessed different exotoxin gene profiles (eg, Panton Valentine leukocidin
      genes) compared with health care-associated isolates. CONCLUSIONS: Community
      associated and health care-associated MRSA cases differ demographically and
      clinically, and their respective isolates are microbiologically distinct. This
      suggests that most community-associated MRSA strains did not originate in health
      care settings, and that their microbiological features may have contributed to
      their emergence in the community. Clinicians should be aware that therapy with
      beta-lactam antimicrobials can no longer be relied on as the sole empiric therapy
      for severely ill outpatients whose infections may be staphylococcal in origin.

PMID- 14665660
TI  - Secular trends in nosocomial infections and mortality associated with noninvasive
      ventilation in patients with exacerbation of COPD and pulmonary edema.
AB  - CONTEXT: Randomized controlled trials have shown that the use of noninvasive
      ventilation (NIV) reduces the need for endotracheal intubation and invasive
      mechanical ventilation and reduces complication rates and mortality in selected
      groups of patients. But whether these benefits translate to a clinical setting is
      unclear. OBJECTIVE: To evaluate longitudinally the routine implementation of NIV
      and its effect on patients admitted to the intensive care unit (ICU) with acute
      exacerbation of chronic obstructive pulmonary disease (COPD) or severe
      cardiogenic pulmonary edema (CPE). DESIGN: Retrospective, observational cohort
      study using prospectively collected data from January 1, 1994, through December
      31, 2001. SETTING: A 26-bed medical intensive care unit (ICU) of a French
      university referral hospital. PARTICIPANTS: A cohort of 479 consecutive patients
      ventilated for acute exacerbation of COPD or CPE. MAIN OUTCOME MEASURES: The ICU
      mortality and incidence rates of ICU-acquired infections. RESULTS: A significant
      increase in NIV use and a concomitant decrease in mortality and ICU-acquired
      infection rates were observed over the study years. With adjustment for relevant
      covariates and propensity scores, NIV was identified as an independent factor
      linked with a reduced risk of death in the cohort (odds ratio [OR], 0.37; 95%
      confidence interval [CI], 0.18-0.78), whereas a high severity score on admission
      (OR, 1.05; 95% CI, 1.01-1.10) and the occurrence of a nosocomial infection (OR,
      3.08; 95% CI, 1.62-5.84) were independently associated with death. Rates of ICU
      acquired pneumonia decreased from 20% in 1994 to 8% in 2001 (P =.04). CONCLUSION:
      Implementing routine use of NIV in critically ill patients with acute
      exacerbation of COPD or severe CPE was associated with improved survival and
      reduction of nosocomial infections.

PMID- 14665661
TI  - Perceptions of medical school deans and state medical society executives about
      physician supply.
AB  - CONTEXT: Physician shortages are appearing, yet controversy about their
      significance and uncertainty about their remedy exist. OBJECTIVES: To sample the
      perceptions of medical school deans and state medical society executives about
      the adequacy of physician supply, to determine the perceived impact of any
      shortages on medical schools, and to assess the capacity of medical schools to
      expand. DESIGN, SETTING, AND PARTICIPANTS: Medical school deans in the United
      States and Puerto Rico were surveyed by means of a structured questionnaire, and
      officials of US state medical societies were queried by means of open-ended
      telephone interviews. Information was obtained from 58% of medical school deans
      and 86% of state medical society executives. MAIN OUTCOME MEASURE: Reported
      perceptions of shortages or surpluses of physicians by specialty and plans to
      increase medical school class size. RESULTS: Approximately 85% of both deans and
      medical society respondents perceived shortages of physicians, usually in
      multiple specialties, while 10% perceived surpluses, usually coexisting with
      shortages. Among deans reporting shortages, 83% described a negative impact on
      their schools. Recent or planned increases in class size were reported by 27% of
      deans and expansion capacity by another 34%, but 7% noted recent decreases in
      class size. Applied generally, these changes in class size could yield 7.6%
      additional matriculants annually. CONCLUSIONS: Physician shortages are prevalent
      and they are negatively affecting medical schools. Little capacity exists to
      alleviate these shortages through class size expansion.

PMID- 14665662
TI  - Fetal alcohol spectrum disorder.

PMID- 14665663
TI  - Inflammation, hypertension, and the metabolic syndrome.

PMID- 14665664
TI  - Combined T4 and T3 therapy--back to the drawing board.

PMID- 14665665
TI  - JAMA patient page. Hypothyroidism.

PMID- 14665666
TI  - Ecsit-ement on the crossroads of Toll and BMP signal transduction.

PMID- 14665667
TI  - Two for the price of one: a bifunctional intron-encoded DNA endonuclease-RNA
      maturase.

PMID- 14665668
TI  - Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized
      estradiol.
AB  - A matured megakaryocyte releases thousands of platelets through a drastic
      morphological change, proplatelet formation (PPF). The megakaryocyte/erythrocyte
      specific transcription factor, p45 NF-E2, is essential for initiating PPF, but
      the factor regulating PPF has not been identified. Here we report that estradiol
      synthesized in megakaryocytes triggers PPF. We demonstrate that a key enzyme for
      steroid hormone biosynthesis, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), is
      a target of p45 NF-E2, and rescues PPF of p45 NF-E2-deficient megakaryocytes. We
      also show that estradiol is synthesized within megakaryocytes, and that
      extracellular estradiol stimulates PPF, inhibition of 3beta-HSD activity blocks
      PPF, and estrogen receptor antagonists inhibit platelet production in vivo. We
      conclude that autocrine estradiol action regulates platelet production by
      triggering PPF.

PMID- 14665669
TI  - The initial somitic phase of Myf5 expression requires neither Shh signaling nor
      Gli regulation.
AB  - Myf5, the skeletal muscle determination gene, is first expressed in the dorso
      medial aspect of the somite under the control of an element we have called the
      early epaxial enhancer. It has subsequently been reported that this enhancer is a
      direct target of Shh signaling mediated by Gli transcription factors (Gustafsson
      et al. 2002). We here demonstrate that activation of Myf5 expression depends on
      neither Shh function nor an intact Gli binding site, although the Gli site is
      necessary for continuation of expression. We suggest that the discrepancy is due
      to the existence of specific interactions between the enhancer and the Myf5
      promoter.

PMID- 14665670
TI  - The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice
      but induces a myogenic gain-of-function phenotype with ligand-independent
      activation of Met signaling in vivo.
AB  - Pax3 is a key transcription factor implicated in development and human disease.
      To dissect the role of Pax3 in myogenesis and establish whether it is a repressor
      or activator, we generated loss- and gain-of-function alleles by targeting an
      nLacZ reporter and a sequence encoding the oncogenic fusion protein PAX3-FKHR
      into the Pax3 locus. Rescue of the Pax3 mutant phenotypes by PAX3-FKHR suggests
      that Pax3 acts as a transcriptional activator during embryogenesis. This is
      confirmed by a Pax reporter mouse. However, mice expressing PAX3-FKHR display
      developmental defects, including ectopic delamination and inappropriate migration
      of muscle precursor cells. These events result from overexpression of c-met,
      leading to constitutive activation of Met signaling, despite the absence of the
      ligand SF/HGF. Haploinsufficiency of c-met rescues this phenotype, confirming the
      direct genetic link with Pax3. The gain-of-function phenotype is also
      characterized by overactivation of MyoD. The consequences of PAX3-FKHR myogenic
      activity in the limbs and cervical and thoracic regions point to differential
      regulation of muscle growth and patterning. This gain-of-function allele provides
      a new approach to the molecular and cellular analysis of the role of Pax3 and of
      its target genes in vivo.

PMID- 14665671
TI  - Senseless acts as a binary switch during sensory organ precursor selection.
AB  - During sensory organ precursor (SOP) specification, a single cell is selected
      from a proneural cluster of cells. Here, we present evidence that Senseless
      (Sens), a zinc-finger transcription factor, plays an important role in this
      process. We show that Sens is directly activated by proneural proteins in the
      presumptive SOPs and a few cells surrounding the SOP in most tissues. In the
      cells that express low levels of Sens, it acts in a DNA-binding-dependent manner
      to repress transcription of proneural genes. In the presumptive SOPs that express
      high levels of Sens, it acts as a transcriptional activator and synergizes with
      proneural proteins. We therefore propose that Sens acts as a binary switch that
      is fundamental to SOP selection.

PMID- 14665672
TI  - The Drosophila cell cycle kinase PAN GU forms an active complex with PLUTONIUM
      and GNU to regulate embryonic divisions.
AB  - Early embryonic cell cycles in Drosophila consist of rapidly alternating S and M
      phases. Three genes, pan gu (png), plutonium (plu), and giant nuclei (gnu)
      coordinate these early S-M cycles by ensuring adequate Cyclin B protein levels.
      Mutations in any of these genes result in unregulated DNA replication and a lack
      of mitosis ("giant nuclei" phenotype). png encodes a serine/threonine protein
      kinase, and plu and gnu encode small, novel proteins. We show that PNG, PLU, and
      GNU constitute a novel protein kinase complex that specifically regulates S-M
      cell cycles. All three proteins are required for PNG kinase activity and are
      phosphorylated by PNG in vitro. Yeast two-hybrid screening revealed a direct
      interaction between PNG and PLU, and their co-expression is required for physical
      association and activation of PNG kinase. Artificial dimerization of PLU via
      fusion to either GST or FK506 binding protein (in the presence of dimerizing
      agent) abrogates the requirement for GNU to activate PNG kinase. We propose a
      model in which GNU normally regulates embryonic cell cycles by promoting
      transient dimerization of a core PNG/PLU complex, thereby stimulating PNG kinase
      activity.

PMID- 14665673
TI  - CcpA-dependent carbon catabolite repression in bacteria.
AB  - Carbon catabolite repression (CCR) by transcriptional regulators follows
      different mechanisms in gram-positive and gram-negative bacteria. In gram
      positive bacteria, CcpA-dependent CCR is mediated by phosphorylation of the
      phosphoenolpyruvate:sugar phosphotransferase system intermediate HPr at a serine
      residue at the expense of ATP. The reaction is catalyzed by HPr kinase, which is
      activated by glycolytic intermediates. In this review, the distribution of CcpA
      dependent CCR among bacteria is investigated by searching the public databases
      for homologues of HPr kinase and HPr-like proteins throughout the bacterial
      kingdom and by analyzing their properties. Homologues of HPr kinase are commonly
      observed in the phylum Firmicutes but are also found in the phyla Proteobacteria,
      Fusobacteria, Spirochaetes, and Chlorobi, suggesting that CcpA-dependent CCR is
      not restricted to gram-positive bacteria. In the alpha and beta subdivisions of
      the Proteobacteria, the presence of HPr kinase appears to be common, while in the
      gamma subdivision it is more of an exception. The genes coding for the HPr kinase
      homologues of the Proteobacteria are in a gene cluster together with an HPr-like
      protein, termed XPr, suggesting a functional relationship. Moreover, the XPr
      proteins contain the serine phosphorylation sequence motif. Remarkably, the
      analysis suggests a possible relation between CcpA-dependent gene regulation and
      the nitrogen regulation system (Ntr) found in the gamma subdivision of the
      Proteobacteria. The relation is suggested by the clustering of CCR and Ntr
      components on the genome of members of the Proteobacteria and by the close
      phylogenetic relationship between XPr and NPr, the HPr-like protein in the Ntr
      system. In bacteria in the phylum Proteobacteria that contain HPr kinase and XPr,
      the latter may be at the center of a complex regulatory network involving both
      CCR and the Ntr system.

PMID- 14665674
TI  - Bioprospecting for microbial endophytes and their natural products.
AB  - Endophytic microorganisms are to be found in virtually every plant on earth.
      These organisms reside in the living tissues of the host plant and do so in a
      variety of relationships, ranging from symbiotic to slightly pathogenic. Because
      of what appears to be their contribution to the host plant, the endophytes may
      produce a plethora of substances of potential use to modern medicine,
      agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants,
      and anticancer compounds are only a few examples of what has been found after the
      isolation, culture, purification, and characterization of some choice endophytes
      in the recent past. The potential prospects of finding new drugs that may be
      effective candidates for treating newly developing diseases in humans, plants,
      and animals are great.

PMID- 14665676
TI  - On the evolution of structure in aminoacyl-tRNA synthetases.
AB  - The aminoacyl-tRNA synthetases are one of the major protein components in the
      translation machinery. These essential proteins are found in all forms of life
      and are responsible for charging their cognate tRNAs with the correct amino acid.
      The evolution of the tRNA synthetases is of fundamental importance with respect
      to the nature of the biological cell and the transition from an RNA world to the
      modern world dominated by protein-enzymes. We present a structure-based phylogeny
      of the aminoacyl-tRNA synthetases. By using structural alignments of all of the
      aminoacyl-tRNA synthetases of known structure in combination with a new measure
      of structural homology, we have reconstructed the evolutionary history of these
      proteins. In order to derive unbiased statistics from the structural alignments,
      we introduce a multidimensional QR factorization which produces a nonredundant
      set of structures. Since protein structure is more highly conserved than protein
      sequence, this study has allowed us to glimpse the evolution of protein structure
      that predates the root of the universal phylogenetic tree. The extensive sequence
      based phylogenetic analysis of the tRNA synthetases (Woese et al., Microbiol.
      Mol. Biol. Rev. 64:202-236, 2000) has further enabled us to reconstruct the
      complete evolutionary profile of these proteins and to make connections between
      major evolutionary events and the resulting changes in protein shape. We also
      discuss the effect of functional specificity on protein shape over the complex
      evolutionary course of the tRNA synthetases.

PMID- 14665675
TI  - Recent advances in petroleum microbiology.
AB  - Recent advances in molecular biology have extended our understanding of the
      metabolic processes related to microbial transformation of petroleum
      hydrocarbons. The physiological responses of microorganisms to the presence of
      hydrocarbons, including cell surface alterations and adaptive mechanisms for
      uptake and efflux of these substrates, have been characterized. New molecular
      techniques have enhanced our ability to investigate the dynamics of microbial
      communities in petroleum-impacted ecosystems. By establishing conditions which
      maximize rates and extents of microbial growth, hydrocarbon access, and
      transformation, highly accelerated and bioreactor-based petroleum waste
      degradation processes have been implemented. Biofilters capable of removing and
      biodegrading volatile petroleum contaminants in air streams with short substrate
      microbe contact times (<60 s) are being used effectively. Microbes are being
      injected into partially spent petroleum reservoirs to enhance oil recovery.
      However, these microbial processes have not exhibited consistent and effective
      performance, primarily because of our inability to control conditions in the
      subsurface environment. Microbes may be exploited to break stable oilfield
      emulsions to produce pipeline quality oil. There is interest in replacing
      physical oil desulfurization processes with biodesulfurization methods through
      promotion of selective sulfur removal without degradation of associated carbon
      moieties. However, since microbes require an environment containing some water, a
      two-phase oil-water system must be established to optimize contact between the
      microbes and the hydrocarbon, and such an emulsion is not easily created with
      viscous crude oil. This challenge may be circumvented by application of the
      technology to more refined gasoline and diesel substrates, where aqueous
      hydrocarbon emulsions are more easily generated. Molecular approaches are being
      used to broaden the substrate specificity and increase the rates and extents of
      desulfurization. Bacterial processes are being commercialized for removal of
      H(2)S and sulfoxides from petrochemical waste streams. Microbes also have
      potential for use in removal of nitrogen from crude oil leading to reduced nitric
      oxide emissions provided that technical problems similar to those experienced in
      biodesulfurization can be solved. Enzymes are being exploited to produce added
      value products from petroleum substrates, and bacterial biosensors are being used
      to analyze petroleum-contaminated environments.

PMID- 14665677
TI  - Quorum sensing in nitrogen-fixing rhizobia.
AB  - Members of the rhizobia are distinguished for their ability to establish a
      nitrogen-fixing symbiosis with leguminous plants. While many details of this
      relationship remain a mystery, much effort has gone into elucidating the
      mechanisms governing bacterium-host recognition and the events leading to
      symbiosis. Several signal molecules, including plant-produced flavonoids and
      bacterially produced nodulation factors and exopolysaccharides, are known to
      function in the molecular conversation between the host and the symbiont. Work by
      several laboratories has shown that an additional mode of regulation, quorum
      sensing, intercedes in the signal exchange process and perhaps plays a major role
      in preparing and coordinating the nitrogen-fixing rhizobia during the
      establishment of the symbiosis. Rhizobium leguminosarum, for example, carries a
      multitiered quorum-sensing system that represents one of the most complex
      regulatory networks identified for this form of gene regulation. This review
      focuses on the recent stream of information regarding quorum sensing in the
      nitrogen-fixing rhizobia. Seminal work on the quorum-sensing systems of R.
      leguminosarum bv. viciae, R. etli, Rhizobium sp. strain NGR234, Sinorhizobium
      meliloti, and Bradyrhizobium japonicum is presented and discussed. The latest
      work shows that quorum sensing can be linked to various symbiotic phenomena
      including nodulation efficiency, symbiosome development, exopolysaccharide
      production, and nitrogen fixation, all of which are important for the
      establishment of a successful symbiosis. Many questions remain to be answered,
      but the knowledge obtained so far provides a firm foundation for future studies
      on the role of quorum-sensing mediated gene regulation in host-bacterium
      interactions.

PMID- 14665681
TI  - Two-dimensional Blue native/SDS gel electrophoresis of multi-protein complexes
      from whole cellular lysates: a proteomics approach.
AB  - Identification and characterization of multi-protein complexes is an important
      step toward an integrative view of protein-protein interaction networks that
      determine protein function and cell behavior. The limiting factor for identifying
      protein complexes is the method for their separation. Blue native PAGE (BN-PAGE)
      permits a high-resolution separation of multi-protein complexes under native
      conditions. To date, BN-PAGE has only been applicable to purified material. Here,
      we show that dialysis permits the analysis of multi-protein complexes of whole
      cellular lysates by BN-PAGE. We visualized different multi-protein complexes by
      immunoblotting including forms of the eukaryotic proteasome. Complex dynamics
      after gamma interferon stimulation of cells was studied, and an antibody shift
      assay was used to detect protein-protein interactions in BN-PAGE. Furthermore, we
      identified defined protein complexes of various proteins including the tumor
      suppressor p53 and c-Myc. Finally, we identified multi-protein complexes via mass
      spectrometry, showing that the method has a wide potential for functional
      proteomics.

PMID- 14665679
TI  - RNA interference: biology, mechanism, and applications.
AB  - Double-stranded RNA-mediated interference (RNAi) is a simple and rapid method of
      silencing gene expression in a range of organisms. The silencing of a gene is a
      consequence of degradation of RNA into short RNAs that activate ribonucleases to
      target homologous mRNA. The resulting phenotypes either are identical to those of
      genetic null mutants or resemble an allelic series of mutants. Specific gene
      silencing has been shown to be related to two ancient processes, cosuppression in
      plants and quelling in fungi, and has also been associated with regulatory
      processes such as transposon silencing, antiviral defense mechanisms, gene
      regulation, and chromosomal modification. Extensive genetic and biochemical
      analysis revealed a two-step mechanism of RNAi-induced gene silencing. The first
      step involves degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25
      nucleotides long, by an RNase III-like activity. In the second step, the siRNAs
      join an RNase complex, RISC (RNA-induced silencing complex), which acts on the
      cognate mRNA and degrades it. Several key components such as Dicer, RNA-dependent
      RNA polymerase, helicases, and dsRNA endonucleases have been identified in
      different organisms for their roles in RNAi. Some of these components also
      control the development of many organisms by processing many noncoding RNAs,
      called micro-RNAs. The biogenesis and function of micro-RNAs resemble RNAi
      activities to a large extent. Recent studies indicate that in the context of
      RNAi, the genome also undergoes alterations in the form of DNA methylation,
      heterochromatin formation, and programmed DNA elimination. As a result of these
      changes, the silencing effect of gene functions is exercised as tightly as
      possible. Because of its exquisite specificity and efficiency, RNAi is being
      considered as an important tool not only for functional genomics, but also for
      gene-specific therapeutic activities that target the mRNAs of disease-related
      genes.

PMID- 14665682
TI  - Auditory modeling gets an edge.

PMID- 14665683
TI  - Spinal cord injury reveals unexpected function of cutaneous receptors.

PMID- 14665684
TI  - Independent processing of the temporal and ordinal structure of movement
      sequences.
AB  - We investigated if the temporal and ordinal structures of sequences can be
      represented and learned independently. In Experiment 1, subjects learned three
      rhythmic sequences of key presses with the right index finger: Combined consisted
      of nine key presses with a corresponding temporal structure of eight intervals;
      Temporal had the temporal structure of Combined but was performed on one key;
      Ordinal had the ordinal structure of Combined but an isochronous rhythm. Subjects
      were divided into two groups. Group 1 first learned Combined, then Temporal and
      Ordinal; Group 2 first learned Temporal and Ordinal, then Combined. Strong
      transfer effects were seen in both groups. In Group 1, having learned combined
      facilitated the learning of the temporal (Temporal) or ordinal (Ordinal) sequence
      alone; in Group 2, having learned Temporal and Ordinal facilitated the learning
      of Combined, where the two are combined. This supports that subjects had formed
      independent temporal and ordinal representations. In Experiment 2, we
      investigated if these can be learned independently. Subjects repeatedly
      reproduced sequences with fixed temporal and random ordinal structure; random
      temporal and fixed ordinal structure; and random temporal and ordinal structures.
      Temporal and ordinal learning was seen only in the first and second sequences,
      respectively. In summary, we provide evidence for the existence of independent
      systems for learning and representation of ordinal and temporal sequences and for
      implicit learning of temporal sequences. This may be important for fast learning
      and flexibility in motor control.

PMID- 14665685
TI  - Cerebellar activation during copying geometrical shapes.
AB  - We studied functional MRI activation in the cerebellum during copying 9
      geometrical shapes (equilateral triangle, isosceles triangle, square, diamond,
      vertical trapezoid, pentagon, hexagon, circle, and vertical lemniscate). Twenty
      subjects were imaged during 3 consecutive 45-s periods (rest, visual
      presentation, and copying). First, there was a positive relation between
      cerebellar activation and the peak speed of individual movements. This effect was
      strongest in the lateral and posterior ipsilateral cerebellum but it was also
      present in the paramedian zones of both cerebellar hemispheres and in the vermis.
      A finer grain analysis of the relations between the time course of the blood
      oxygenation level-dependent activation and movement parameters revealed a
      significant relation to hand position and speed but not to acceleration. Second,
      there was a significant relation between the intensity of voxel activation during
      visual presentation and the speed of the upcoming movement. The spatial
      distribution of these voxels was very similar to that of the voxels activated
      during copying, indicating that the cerebellum might be involved in motor
      rehearsal, in addition to its role during movement execution. Finally, a factor
      analysis of the intensity of activated voxels in the ipsilateral cerebellum
      during copying (adjusted for the speed effect) extracted 3 shape factors. Factor
      1 reflected "roundness," factor 2 "upward pointing," and factor 3 "pointing (up
      or down) and elongation." These results link cerebellar activation to more
      global, spatial aspects of copying.

PMID- 14665687
TI  - Saccade adaptation in response to altered arm dynamics.
AB  - The delays in sensorimotor pathways pose a formidable challenge to the
      implementation of stable error feedback control, and yet the intact brain has
      little trouble maintaining limb stability. How is this achieved? One idea is that
      feedback control depends not only on delayed proprioceptive feedback but also on
      internal models of limb dynamics. In theory, an internal model allows the brain
      to predict limb position. Earlier we had found that during reaching, the brain
      estimates hand position in real-time in a coordinate system that can be used for
      generating saccades. Here we tested the idea that the estimate of hand position,
      as expressed through saccades, depends on an internal model that adapts to
      dynamics of the arm. We focused on the behavior of the eyes as perturbations were
      applied to the unseen hand. We found that when the hand was perturbed from stable
      posture with a 100-ms force pulse of random direction and magnitude, a saccade
      was generated on average at 182 ms postpulse onset to a position that was an
      unbiased estimate of real-time hand position. To test whether planning of
      saccades depended on an internal model of arm dynamics, arm dynamics were altered
      either predictably or unpredictably during the postpulse period. When arm
      dynamics were predictable, saccade amplitudes changed to reflect the change in
      the arm's behavior. We suggest that proprioceptive feedback from the arm is
      integrated into an adaptable internal model that computes an estimate of current
      hand position in eye-centered coordinates.

PMID- 14665680
TI  - A continuum of anionic charge: structures and functions of D-alanyl-teichoic
      acids in gram-positive bacteria.
AB  - Teichoic acids (TAs) are major wall and membrane components of most gram-positive
      bacteria. With few exceptions, they are polymers of glycerol-phosphate or ribitol
      phosphate to which are attached glycosyl and D-alanyl ester residues. Wall TA is
      attached to peptidoglycan via a linkage unit, whereas lipoteichoic acid is
      attached to glycolipid intercalated in the membrane. Together with peptidoglycan,
      these polymers make up a polyanionic matrix that functions in (i) cation
      homeostasis; (ii) trafficking of ions, nutrients, proteins, and antibiotics;
      (iii) regulation of autolysins; and (iv) presentation of envelope proteins. The
      esterification of TAs with D-alanyl esters provides a means of modulating the net
      anionic charge, determining the cationic binding capacity, and displaying cations
      in the wall. This review addresses the structures and functions of D-alanyl-TAs,
      the D-alanylation system encoded by the dlt operon, and the roles of TAs in cell
      growth. The importance of dlt in the physiology of many organisms is illustrated
      by the variety of mutant phenotypes. In addition, advances in our understanding
      of D-alanyl ester function in virulence and host-mediated responses have been
      made possible through targeted mutagenesis of dlt. Studies of the mechanism of D
      alanylation have identified two potential targets of antibacterial action and
      provided possible screening reactions for designing novel agents targeted to D
      alanyl-TA synthesis.

PMID- 14665686
TI  - Availability of low-threshold Ca2+ current in retinal ganglion cells.
AB  - Spiking in central neurons depends on the availability of inward and outward
      currents activated by depolarization and on the activation and priming of
      currents by hyperpolarization. Of these processes, priming by hyperpolarization
      is the least described. In the case of T-type Ca2+ current availability, the
      interplay of hyperpolarization and depolarization has been studied most
      completely in expression systems, in part because of the difficulty of
      pharmacologically separating the Ca2+ currents of native neurons. To facilitate
      understanding of this current under physiological conditions, we measured T-type
      current of isolated goldfish retinal ganglion cells with perforated-patch voltage
      clamp methods in solutions containing a normal extracellular Ca2+ concentration.
      The voltage sensitivities and rates of current activation, inactivation,
      deactivation, and recovery from inactivation were similar to those of expressed
      alpha1G (CaV3.1) Ca2+ channel clones, except that the rate of deactivation was
      significantly faster. We reproduced the amplitude and kinetics of measured T
      currents with a numerical simulation based on a kinetic model developed for an
      alpha1G Ca2+ channel. Finally, we show that this model predicts the increase of T
      type current made available between resting potential and spike threshold by
      repetitive hyperpolarizations presented at rates that are within the bandwidth of
      signals processed in situ by these neurons.

PMID- 14665688
TI  - Site-specific recombination by the DDE family member mobile element IS30
      transposase.
AB  - DNA rearrangements carried out by site-specific recombinases and transposases
      (Tpases) show striking similarities despite the wide spectrum of the catalytic
      mechanisms involved in the reactions. Here, we show that the bacterial insertion
      sequence (IS)30 element can act similarly to site-specific systems. We have
      developed an inversion system using IS30 Tpase and a viable lambda phage, where
      the integration/excision system is replaced with IS30. Both models have been
      proved to operate analogously to their natural counterpart, confirming that a DDE
      family Tpase is able to fulfill the functions of site-specific recombinases. This
      work demonstrates that distinction between transposition and site-specific
      recombination becomes blurred, because both functions can be fulfilled by the
      same enzyme, and both types of rearrangements can be achieved by the same
      catalytic mechanisms.

PMID- 14665678
TI  - Molecular basis of bacterial outer membrane permeability revisited.
AB  - Gram-negative bacteria characteristically are surrounded by an additional
      membrane layer, the outer membrane. Although outer membrane components often play
      important roles in the interaction of symbiotic or pathogenic bacteria with their
      host organisms, the major role of this membrane must usually be to serve as a
      permeability barrier to prevent the entry of noxious compounds and at the same
      time to allow the influx of nutrient molecules. This review summarizes the
      development in the field since our previous review (H. Nikaido and M. Vaara,
      Microbiol. Rev. 49:1-32, 1985) was published. With the discovery of protein
      channels, structural knowledge enables us to understand in molecular detail how
      porins, specific channels, TonB-linked receptors, and other proteins function. We
      are now beginning to see how the export of large proteins occurs across the outer
      membrane. With our knowledge of the lipopolysaccharide-phospholipid asymmetric
      bilayer of the outer membrane, we are finally beginning to understand how this
      bilayer can retard the entry of lipophilic compounds, owing to our increasing
      knowledge about the chemistry of lipopolysaccharide from diverse organisms and
      the way in which lipopolysaccharide structure is modified by environmental
      conditions.

PMID- 14665689
TI  - Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments.
AB  - Observations that beta-sheet proteins form amyloid fibrils under at least
      partially denaturing conditions has raised questions as to whether these fibrils
      assemble by docking of preformed beta-structure or by association of unfolded
      polypeptide segments. By using alpha-helical protein apomyoglobin, we show that
      the ease of fibril assembly correlates with the extent of denaturation. By
      contrast, monomeric beta-sheet intermediates could not be observed under the
      conditions of fibril formation. These data suggest that amyloid fibril formation
      from apomyoglobin depends on disordered polypeptide segments and conditions that
      are selectively unfavorable to folding. However, it is inevitable that such
      conditions often stabilize protein folding intermediates.

PMID- 14665690
TI  - Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left
      ventricular remodeling.
AB  - Left ventricular remodeling that occurs after myocardial infarction (MI) and
      pressure overload is generally accepted as a determinant of the clinical course
      of heart failure. The molecular mechanism of this process, however, remains to be
      elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated
      protein kinase kinase kinase that plays an important role in stress-induced
      apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1
      is involved in development of left ventricular remodeling. ASK-/- hearts showed
      no morphological or histological defects. Echocardiography and cardiac
      catheterization revealed normal global structure and function. Left ventricular
      structural and functional remodeling were determined 4 weeks after coronary
      artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had
      significantly smaller increases in left ventricular end-diastolic and end
      systolic ventricular dimensions and smaller decreases in fractional shortening in
      both experimental models compared with WT mice. The number of terminal
      deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes
      after MI or TAC was decreased in ASK-/- compared with that in WT mice.
      Overexpression of a constitutively active mutant of ASK1 induced apoptosis in
      isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were
      resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased
      ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important
      role in regulating left ventricular remodeling by promoting apoptosis.

PMID- 14665692
TI  - Differential survival of solitary and aggregated bacterial cells promotes
      aggregate formation on leaf surfaces.
AB  - The survival of individual Pseudomonas syringae cells was determined on bean leaf
      surfaces maintained under humid conditions or periodically exposed to desiccation
      stress. Cells of P. syringae strain B728a harboring a GFP marker gene were
      visualized by epifluorescence microscopy, either directly in situ or after
      recovery from leaves, and dead cells were identified as those that were stained
      with propidium iodide in such populations. Under moist, conducive conditions on
      plants, the proportion of total live cells was always high, irrespective of their
      aggregated state. In contrast, the proportion of the total cells that remained
      alive on leaves that were periodically exposed to desiccation stress decreased
      through time and was only approximately 15% after 5 days. However, the fraction
      of cells in large aggregates that were alive on such plants in both condition was
      much higher than more solitary cells. Immediately after inoculation, cells were
      randomly distributed over the leaf surface and no aggregates were observed.
      However, a very aggregated pattern of colonization was apparent within 7 days,
      and >90% of the living cells were located in aggregates of 100 cells or more. Our
      results strongly suggest that, although conducive conditions favor aggregate
      formation, such cells are much more capable of tolerating environmental stresses,
      and the preferential survival of cells in aggregates promotes a highly clustered
      spatial distribution of bacteria on leaf surfaces.

PMID- 14665691
TI  - Increased phosphorylation of the neuronal L-type Ca(2+) channel Ca(v)1.2 during
      aging.
AB  - An increase in Ca2+ influx through L-type Ca2+ channels is thought to contribute
      to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease.
      The molecular basis of the age-dependent up-regulation in neuronal L-type Ca2+
      channel activity is largely unknown. We show that phosphorylation of the L-type
      channel Cav1.2 by cAMP-dependent protein kinase is increased >2-fold in the
      hippocampus of aged rats. The hippocampus is critical for learning and is one of
      the first brain regions to be affected in Alzheimer's disease. Phosphorylation of
      Cav1.2 by cAMP-dependent protein kinase strongly enhances its activity.
      Therefore, increased Cav1.2 phosphorylation may account for a substantial portion
      of the age-related rise in neuronal Ca2+ influx and its neuropathological
      consequences.

PMID- 14665693
TI  - Binding of Plasmodium falciparum-infected erythrocytes to the membrane-bound form
      of Fractalkine/CX3CL1.
AB  - Plasmodium falciparum-infected erythrocytes (pRBCs) adhere to the endothelium via
      receptors expressed on the surface of vascular endothelial cells (EC) and
      sequester in the microvasculature of several organs and block the blood
      circulation. The sequestration, which involves receptors, may be related to the
      severity of malaria. Here, we report that pRBCs bind to the membrane-bound form
      of Fractalkine/CX3CL1 (FKN), which is expressed on the surface of vascular EC in
      various organs. pRBCs adhered to FKN on the surface of FKN cDNA-transfected
      Chinese hamster ovary cells (CHO-FKN cells). Both the recombinant human FKN
      chemokine domain (FKN-CD) and anti-FKN-CD antibody efficiently blocked adherence
      of pRBCs to CHO-FKN cells. Similar to binding between FKN and FKN receptor on
      blood mononuclear cells, two amino acid residues, Lys-7 and Arg-47 within FKN-CD,
      were critical for FKN-pRBC binding. Immunohistological analysis revealed the
      expression of FKN on EC at the site of sequestration in the brain of a patient
      with cerebral malaria. These results suggest that the membrane-bound form of FKN
      acts as a receptor for pRBCs, and this may contribute to furthering our present
      understanding of cytoadherence in the pathology of falciparum malaria.

PMID- 14665694
TI  - IkappaBalpha/IkappaBepsilon deficiency reveals that a critical NF-kappaB dosage
      is required for lymphocyte survival.
AB  - In most cells, the NF-kappaB transcription factor is sequestered in the cytoplasm
      by interaction with inhibitory proteins, the IkappaBs. Here, we show that
      combined IkappaBalpha/IkappaBepsilon deficiency in mice leads to neonatal death,
      elevated kappaB binding activity, overexpression of NF-kappaB target genes, and
      disruption of lymphocyte production. In IkappaBalpha/IkappaBepsilon-deficient
      fetuses, B220+IgM+ B cells and single-positive T cells die by apoptosis. In
      adults, IkappaBalpha-/-IkappaBepsilon-/- reconstituted chimeras exhibit a nearly
      complete absence of T and B cells that is not rescued by cotransfer with wild
      type bone marrow. These findings demonstrate that IkappaBs tightly control NF
      kappaB activity in vivo and that increased NF-kappaB activity intrinsically
      impairs lymphocyte survival. Because reduction or rise of NF-kappaB activity
      leads to similar dysfunction, they also reveal that only a narrow window of NF
      kappaB activity is tolerated by lymphocytes.

PMID- 14665695
TI  - Arf tumor suppressor promoter monitors latent oncogenic signals in vivo.
AB  - Induction of the Arf tumor suppressor gene by elevated thresholds of mitogenic
      signals activates a p53-dependent transcriptional response that triggers either
      growth arrest or apoptosis, thereby countering abnormal cell proliferation.
      Conversely, Arf inactivation is associated with tumor development. Expression of
      Arf in tissues of adult mice is difficult to detect, possibly because its
      induction leads to the arrest or elimination of incipient tumor cells. We
      replaced coding sequences of exon 1beta of the mouse cellular Arf gene with a
      cDNA encoding GFP, thereby producing Arf-null animals in which GFP expression is
      driven by the intact Arf promoter. The Arf promoter was induced in several
      biologic settings previously shown to elicit mouse p19Arf expression.
      Inactivation of Arf in this manner led to the outgrowth of tumor cells expressing
      GFP, thereby providing direct evidence that the Arf promoter monitors latent
      oncogenic signals in vivo.

PMID- 14665696
TI  - Gene expression profiles of primary breast tumors maintained in distant
      metastases.
AB  - It has been debated for decades how cancer cells acquire metastatic capability.
      It is unclear whether metastases are derived from distinct subpopulations of
      tumor cells within the primary site with higher metastatic potential, or whether
      they originate from a random fraction of tumor cells. Here we show, by gene
      expression profiling, that human primary breast tumors are strikingly similar to
      the distant metastases of the same patient. Unsupervised hierarchical clustering,
      multidimensional scaling, and permutation testing, as well as the comparison of
      significantly expressed genes within a pair, reveal their genetic similarity. Our
      findings suggest that metastatic capability in breast cancer is an inherent
      feature and is not based on clonal selection.

PMID- 14665698
TI  - The Arg16/Gly beta2-adrenergic receptor polymorphism is associated with altered
      cardiovascular responses to isometric exercise.
AB  - A polymorphism in the gene encoding the beta(2)-adrenergic receptor (arginine or
      glycine at amino acid position 16) is associated with altered vasodilator
      responses to beta(2)-agonists, which may modulate the pressor response to
      endogenous catecholamines during stress. To test the hypothesis that the
      Arg16/Gly polymorphism is associated with differences in acute pressor responses
      to sympathoexcitation, we measured mean arterial pressure (MAP, Finapres) and
      heart rate (HR, ECG) during mental stress (MS), cold pressor test (CPT), and
      handgrip (HG) to fatigue in 31 healthy, nonobese, normotensive adults (mean age
      +/- SE: 31 +/- 1; 16 females). Subjects were homozygous for Gly16 (n = 16) or
      Arg16 (n = 15). Both groups had similar baseline MAP (Arg16, 86 +/- 3 mmHg;
      Gly16, 89 +/- 2 mmHg; P = 0.4) and HR (Arg16, 68 +/- 2 beats/min; Gly16, 65 +/- 3
      beats/min; P = 0.3). For MS and CPT, MAP and HR did not differ between genotype
      groups. Handgrip also produced similar increases in MAP; however, the change in
      HR was greater in the Gly16 homozygotes (P(ANOVA) = 0.001, genotype-by-time
      interaction). During HG, peak HR at fatigue was 100 +/- 4 beats/min for Gly16
      (54% increase from rest) vs. 93 +/- 3 beats/min for Arg16 (37% increase). We
      conclude that the cardiovascular responses to MS and CPT do not differ between
      Gly16 and Arg16 homozygotes. However, the greater HR response to exercise in the
      Gly16 homozygotes may serve to maintain the pressor response (increased cardiac
      output) in the face of augmented peripheral vasodilation (decreased total
      peripheral resistance) in this group.

PMID- 14665697
TI  - Cation--chloride cotransporters mediate neural computation in the retina.
AB  - The ability of directionally selective (DS) retinal ganglion cells to respond
      selectively to stimulus motion in one direction is a classic unresolved example
      of computation in a local neural circuit. Recent evidence indicates that DS
      responses occur first in the retina in the dendrites of starburst amacrine cells
      (interneurons presynaptic to the ganglion cells). We report that the directional
      responses of starburst-cell dendrites and DS ganglion cells are highly sensitive
      to the polarity of the transmembrane chloride gradient. Reducing the
      transmembrane chloride gradient by ion substitution or by blocking the K-Cl
      cotransporter resulted in the starburst cells responding equally to light moving
      in opposite directions. Conversely, increasing the chloride gradient by blocking
      the Na-K-Cl cotransporter eliminated responses to light moving in either
      direction. Moreover, in each case, blocking the chloride cotransporters or
      reducing the transmembrane chloride gradient eliminated the directional responses
      of DS ganglion cells in a manner opposite that of the starburst cells. These
      results indicate that chloride cotransporters play a key role in the generation
      of direction selectivity and that the directional responses of starburst cells
      and DS ganglion cells are exquisitely sensitive to the chloride equilibrium
      potential. The findings further suggest that the directional responses of DS
      ganglion cells are mediated in part by the directional release of gamma
      aminobutyric acid from starburst dendrites and that the asymmetric distribution
      of the two cotransporters along starburst-cell dendrites mediates direction
      selectivity. A model of direction selectivity in the retina that incorporates
      these and other findings is discussed.

PMID- 14665699
TI  - X-linked loci influence spatial navigation performance in Dahl rats.
AB  - Elucidation of natural genetic variations underlying strain or individual
      differences in cognitive function has remained elusive. Here we report the
      identification of two genetic loci that influence spatial navigation in Dahl
      rats. In the Morris water maze test, Dahl R rats exhibited efficient spatial
      navigation, whereas Dahl S rats displayed poor spatial navigation (accuracy).
      Analysis of F1 male progeny of reciprocal crosses between Dahl S and Dahl R
      strains implicated the X chromosome with the impairment in spatial navigation
      observed in Dahl S rats. Quantitative trait locus (QTL) analysis of an (RXS) F2
      male population phenotyped for spatial navigation detected two QTLs on chromosome
      X influencing spatial navigation performance. One QTL (Nav-1, centered at
      DXRat21, significant for linkage) influenced acquisition performance without
      affecting spatial accuracy performance; and the second QTL (Nav-2, centered at
      DXRat25, significant for linkage) affected spatial accuracy performance with no
      detectable effect on acquisition performance. Our results demonstrate X linkage
      of spatial navigation performance in Dahl rats and provide evidence for the
      existence of independent genetic determinants for defined behavioral components
      of spatial navigation.

PMID- 14665700
TI  - Turning it on and off: M-phase promoting factor during meiotic maturation and
      fertilization.
AB  - Maturation (M-phase) promoting factor (MPF) plays a pivotal role in oocytes
      during their maturation. This review concentrates on its function at three
      important time-points. First, its activation during meiotic progression from
      prophase I arrest at germinal vesicle breakdown. Second, its role during the
      transition from meiosis I to meiosis II, a defining feature of meiosis involving
      segregation of homologous chromosomes. Third, maintenance of its activity at
      metaphase II arrest and the necessity for its destruction during oocyte
      activation. An understanding of how oocytes switch it on and turn it off
      underpins much of the basic cell biology of oocyte maturation.

PMID- 14665701
TI  - Differences in connective tissue gene expression between normally functioning,
      polycystic and post-menopausal ovaries.
AB  - Arrested follicular maturation is a characteristic feature of polycystic ovary
      syndrome (PCOS). Follicles mature in ovarian stroma composed of extracellular
      matrix (ECM). However, little is known of the expression of ECM genes in
      polycystic ovaries. The present study compares the expression levels of genes
      coding for collagens, matrix metalloproteinases (MMP), their inhibitors (TIMP)
      and cathepsins in polycystic ovaries using fertile and post-menopausal ovaries as
      controls. In northern analyses, the gene expression profiles of type I and III
      collagen of PCOS samples resembled those observed in normal follicular phase
      ovaries, while mRNA levels of proalpha1(IV) collagen and TIMP-3 mRNA were
      significantly lower in polycystic than control ovaries. During the normal
      menstrual cycle, an increase was observed in MMP-9 gene expression during the
      luteal phase. In post-menopausal ovaries, mRNA levels for type I, III and IV
      collagens and osteonectin were reduced, while the MMP, TIMP (excluding TIMP-3)
      and cathepsins did not reflect this metabolic down-regulation.
      Immunohistochemical staining for MMP-9 and TIMP-4 suggested differences between
      polycystic and normally functioning ovaries. These data demonstrate that normal
      ovarian functions are associated with changes in production and degradation of
      ECM. The alterations observed in the production and/or distribution of type IV
      collagen, TIMP-3 and TIMP-4 suggest involvement of basement membranes in the
      pathogenesis of PCOS.

PMID- 14665702
TI  - Expression pattern of the Y-linked PRY gene suggests a function in apoptosis but
      not in spermatogenesis.
AB  - In this study, we aimed at analysing the expression of the PRY (PTPN-13 like on
      the Y chromosome) gene, located on the Y chromosome, in order to define the
      function of this gene. Active copies of the PRY gene (PRY1 and PRY2) are located
      in the AZFb region. PCR amplification of PRY cDNA indicated that the PRY gene is
      expressed in testicular tissue and ejaculated sperm, but not in Percoll-treated
      sperm. Furthermore, immunocytochemistry on testicular tissue showed the
      expression of the PRY gene in a small number of spermatozoa and spermatids. In
      the ejaculate of the male partner of 18 infertile couples, the PRY protein was
      found in 1.5-51.2% of spermatozoa and in most of the sperm precursor cells. The
      percentage of spermatozoa showing DNA fragmentation was also determined in 13 of
      these samples, by using the TdT (terminal deoxynucleotidyl transferase)-mediated
      dUDP nick-end labelling (TUNEL) reaction. These data correlated with the
      percentage of PRY-positive cells. When double labelling for PRY and DNA
      fragmentation was performed to assess whether PRY-positive cells also show DNA
      fragmentation, we saw that 27-48% of the PRY-positive spermatozoa were also
      positive for the TUNEL reaction. The overall data of RNA analysis,
      immunocytochemistry and the TUNEL reaction indicate that the role of the PRY gene
      in spermatogenesis can be questioned, but suggest its involvement in apoptosis of
      spermatids and spermatozoa.

PMID- 14665703
TI  - Alterations in mitochondrial membrane potential during preimplantation stages of
      mouse and human embryo development.
AB  - Mitochondria are cellular organelles regulating metabolism and cell death
      pathways. This study examined changes in mitochondrial membrane potential
      (deltapsim) throughout the stages of preimplantation development in mouse embryos
      conceived either in vivo or in vitro and human embryos donated to research from
      IVF. Embryos stained with the deltapsim-sensitive dye (JC-1) were quantified for
      the ratio of high- to low-polarized mitochondria using a deconvolution
      microscope. Overall, mouse zygotes and early embryos contain a subset of high
      polarized mitochondria with a progressive increase in the ratio of deltapsim
      observed with increasing cleavage. A transient increase in the ratio of high to
      low deltapsim was observed in in vivo fertilized 2-cell stage embryos, coincident
      with embryonic genome activation in the mouse, but not in 2-cell embryos obtained
      through IVF. We further observed that arrested mouse 2-cell embryos possessed an
      increased ratio of deltapsim compared with non-arrested embryos. In human 8-cell
      embryos we observed an increased ratio of high- to low-polarized mitochondria
      with increasing degrees of embryo fragmentation. We concluded that the pattern of
      mitochondrial membrane potential progressively changes throughout preimplantation
      development, and that an aberrant shift in deltapsim could contribute to, or is
      associated with, decreased developmental potential.

PMID- 14665704
TI  - X-linked inhibitor of apoptosis (XIAP) confers human trophoblast cell resistance
      to Fas-mediated apoptosis.
AB  - Apoptosis occurs in the placenta throughout gestation, with a greater frequency
      near term in comparison to the first trimester. The Fas/FasL system represents
      one of the main apoptotic pathways controlling placental apoptosis. Although
      first trimester trophoblast cells express both Fas and FasL, they are resistant
      to Fas-induced apoptosis. Therefore, trophoblast resistance to Fas-mediated
      apoptosis may be due to the inhibition of the pathway downstream of Fas
      stimulation. Expression levels of X-linked inhibitor of apoptosis (XIAP) were
      recently shown to decrease in third trimester placentas, correlating with an
      increase in placental apoptosis. As a potent caspase inhibitor, XIAP prevents the
      activation of caspase-9 through its BIR3 domain and caspase-3 activation via the
      linker-BIR2 domain. In the present study, high levels of the active form of XIAP
      were detected in first trimester trophoblast cells, whereas term placental tissue
      samples predominantly expressed the inactive form of XIAP. Using a XIAP
      inhibitor, phenoxodiol, we demonstrate that XIAP inactivation sensitizes
      trophoblast cells to Fas stimulation, as evidenced by the anti-Fas mAb-induced
      decrease in trophoblast cell viability and increase in caspase-8, caspase-9 and
      caspase-3 activation. This suggests a functional role for XIAP in the regulation
      of the Fas apoptotic cascade in trophoblast cells during pregnancy.

PMID- 14665705
TI  - Molecular mechanisms involved in GnRH analogue-related apoptosis for uterine
      leiomyomas.
AB  - GnRH agonist therapy is known to reduce uterine leiomyoma volume, although the
      molecular mechanisms responsible for this effect remain poorly understood. In
      this study, we have investigated the molecular mechanisms involved in the anti
      proliferative effect of a GnRH agonist, leuprolide acetate (LA), in uterine
      leiomyomas obtained from six patients treated with LA for 3 months before surgery
      (group B), compared with tumours from six untreated patients (group A). To this
      end, we have evaluated the expression and the activity of molecules involved in
      the regulation of cell survival and proliferation. In group B, the total activity
      of PI3K was reduced by 60% compared with control samples. Furthermore, LA caused
      a reduction of PKB activation of approximately 50%, measured as serine 473
      phosphorylation. In parallel with PKB reduction in LA samples, we observed a 60%
      reduction in the phosphorylation of its substrate BAD. While Bcl-xL/BAD
      association was not significantly modified in LA-treated leiomyomas, BAD/14.3.3
      interaction was reduced, due to a 50% decreased 14.3.3 expression. In addition,
      LA was able to reduce the expression of the antiapoptotic proteins FLIP and
      PED/PEA15 by 70 and 50% respectively, compared with control samples. We next
      evaluated the activation of MAP kinases in leiomyomas. Activation of p42 and p44
      MAP kinase isoforms was increased by 30% in group B. However, the phosphorylation
      of the transcription factor Elk1 was not increased in a similar fashion in LA
      treated leiomyomas compared with group A. Thus, these data suggest that LA
      reduction of leiomyoma volume is mediated at least in part by a decreased
      activation of the PI3K/PKB survival pathway and by the suppression of
      antiapoptotic factors.

PMID- 14665706
TI  - A polymorphism in the CYP17 gene and intrauterine fetal growth restriction.
AB  - Intrauterine fetal growth restriction is a multifactorial disorder, and its
      aetiology includes both environmental and genetic components. We aimed to
      investigate whether maternal genetic polymorphisms of metabolic enzymes affects
      fetal growth and pregnancy duration. Genomic DNA was obtained from 134 women who
      experienced singleton deliveries beyond 24 weeks of gestation. Maternal age,
      birth weight, gestational age at birth and frequencies of fetal growth
      restriction, prematurity and pregnancy-induced hypertension were compared among
      genotypic subgroups of cytochrome p450 (CYP) and glutathione S-transferase (GST)
      genes. The polymorphisms of CYP1A1 (MspI), CYP17 (MspAI) and GSTP1 (BsmAI)
      genotypes, and the presence or absence of GSTM1 and GSTT1 genes were analysed by
      PCR-based methods. The frequency of fetal growth restriction (<10th percentile/<
      1.5 SD; 22.7%/11.4%) in 44 women who were homozygous for the A1 allele (A1A1) of
      CYP17 was significantly higher than that (7.8%/2.2%) in 90 women who carried the
      A2 allele (A1A2/A2A2) of CYP17 (P < 0.05), with an odds ratio =3.41 (95%
      confidence interval = 1.18-9.84). The gestational age at birth (mean +/- SD, 37.5
      +/- 3.1 weeks) in 67 women with GSTM1 null genotype was significantly lower than
      that (38.5 +/- 2.4 weeks) in 67 women who carried GSTM1 (P < 0.05). The
      polymorphism of CYP17 that encodes the cytochrome p450c17alpha enzyme might be
      associated with the pathophysiology underlying fetal growth restriction.

PMID- 14665707
TI  - First trimester trophoblast cells secrete Fas ligand which induces immune cell
      apoptosis.
AB  - Since the invading trophoblast represents a semi-allograft, it should be rejected
      by the mother. It has, therefore, been postulated that during normal pregnancy
      the trophoblast evades the maternal immune system though the establishment of
      immune privilege by triggering the death of activated lymphocytes which may be
      sensitized to paternal alloantigens. Such peripheral tolerance may be directed
      through the Fas/Fas ligand (FasL) apoptotic pathway and mediated by FasL
      expressed by the trophoblast. However, in vivo studies show that membrane
      associated expression of FasL may instead promote allograft rejection, rather
      than protection. The aim of this study was to determine if there is a role for
      FasL in trophoblast immune privilege. In this study, we demonstrate that isolated
      first trimester trophoblast cells lack membrane-associated FasL, but express a
      cytoplasmic form in association with a specialized secretory lysosomal pathway.
      Furthermore, this intracellular FasL is constitutively secreted by trophoblast
      cells via the release of microvesicles. Following disruption of these
      microvesicles, the whole 37 kDa secreted FasL is able to induce T-cell death by
      apoptosis through activation of the Fas pathway. Therefore, we propose that
      secretion of FasL may be one mechanism by which trophoblast cells promote a state
      of immune privilege and, therefore, protect themselves from maternal immune
      recognition.

PMID- 14665708
TI  - Differential kinetics of serum and cervical insulin-like growth factor-binding
      protein-1 during mifepristone-misoprostol-induced medical termination of early
      pregnancy.
AB  - The kinetics of cervical and circulating phosphoisoforms of insulin-like growth
      factor-binding protein-1 (IGFBP-1) in normal and pathological early pregnancy are
      not well known. We investigated the profiles of IGFBP-1 in serum and in cervical
      secretion during medical termination of early pregnancy. Sixteen women requesting
      termination of pregnancy, with <63 days of amenorrhoea, received 200 mg of
      mifepristone on day 0, followed by either oral or vaginal administration of 0.8
      mg of misoprostol on day 2. Serum and cervical swab samples, collected up to 6
      weeks following the beginning of the treatment, were analysed for IGFBP-1 using
      two immunoenzymometric assays recognizing different patterns of IGFBP-1
      phosphoisoforms. Serum mifepristone was also assayed. In the cervical samples,
      IGFBP-1 concentration, measured with both assays, increased substantially 2 days
      following administration of mifepristone. At 3 h after administration of
      misoprostol, IGFBP-1 had further increased several-fold in the cervix, but the
      increase was more pronounced as measured by the assay with preference for the
      amniotic fluid isoforms of IGFBP-1. A strong negative correlation was found
      between the time to abortion and the increase in cervical IGFBP-1 after
      administration of misoprostol, as measured by the assay preferring the
      phosphorylated isoforms of IGFBP-1. At 6 weeks, IGFBP-1 in the cervix had
      decreased to lower than pre-treatment levels, as measured by both assays. In
      serum, both assays showed a significant increase in IGFBP-1 concentrations after
      administration of mifepristone, and the highest values were measured on day 2,
      already before misoprostol administration. Thus, the kinetics of circulating and
      cervical IGFBP-1 differed from each other, indicating different sources and
      regulation of serum and cervical IGFBP-1.

PMID- 14665709
TI  - Preimplantation genetic diagnosis of spinocerebellar ataxia 3 by (CAG)(n) repeat
      detection.
AB  - Spinocerebellar ataxia 3 (SCA3) is an autosomal dominant neurodegenerative
      disorder characterized by variable expression and a variable age of onset.
      SCA3/MJD (Machado-Joseph disease) is caused by an expansion of a (CAG)(n) repeat
      in the MJD1 gene on chromosome 14q32.1. A single cell PCR protocol has been
      developed for preimplantation genetic diagnosis (PGD) of SCA3 to select
      unaffected embryos on the basis of the CAG genotype. Single leukocytes and
      blastomeres served as a single cell amplification test system to determine the
      percentage of allelic drop-out (ADO) and PCR efficiency. Out of 105 tested
      heterozygous single leukocytes, 103 (98.1%) showed a positive amplification
      signal, while five cells (4.9%) showed ADO. Amplification in single blastomeres
      was obtained in 13 out of a total of 14, and ADO was observed in two out of the
      13 single blastomeres. PGD of SCA3 was performed in a couple with paternal
      transmission of the SCA3 allele. Seven embryos were available for biopsy, all
      biopsied blastomeres showed amplification and no ADO occurred. One embryo was
      diagnosed as affected whereas six embryos were diagnosed as unaffected. Two
      unaffected embryos were transferred and resulted in a singleton pregnancy and the
      birth of a healthy girl.

PMID- 14665710
TI  - Heparanase, galectin-3, and tissue factor mRNA are expressed in benign neoplasms
      of the thyroid.
AB  - OBJECTIVE: Heparanase, galectin-3, and tissue factor (TF) are overexpressed in
      solid malignant thyroid tumors. We studied their expression in multinodular
      goiters (MNGs). DESIGN AND METHODS: Thyroid tissue specimens from 15 MNGs were
      obtained during surgery. mRNA expression for galectin-3, heparanase, and TF was
      assessed by RT-PCR. RESULTS: Isolated expressions of heparanase and galectin- 3
      mRNA were expressed in 2 and 4 of the 15 MNGs, respectively; 8/15 MNGs were
      positive for both heparanase and galectin-3. TF mRNA was found in all MNG
      specimens. CONCLUSION: Galectin-3, heparanase, and TF RNA expression is prevalent
      in MNGs. Further studies will be needed to determine the prognostic significance
      of these findings.

PMID- 14665711
TI  - The development of diabetes mellitus in Wistar rats kept on a high-fat/low
      carbohydrate diet for long periods.
AB  - The present study was performed to determine the effect of long-term feeding with
      a high-fat/low-carbohydrate (HF/LC) diet on the onset of type-2 diabetes mellitus
      in normal rats. Male Wistar Imamichi rats were kept on a Control (carbohydrate
      60%, fat 15%) or HF/ LC (carbohydrate 10%, fat 65%) diet for 16 mo. An
      intraperitoneal glucose tolerance test was performed once every 2 mo. Glucose
      tolerance was impaired 2 mo after the start of HF/LC diet feeding, accompanied by
      a decrease in the insulinogenic index. Along with time of HF/LC diet feeding, the
      glucose tolerance was further deteriorated with more serious impairment of
      insulin secretion and sensitivity. At the end of the experiment, 15 of 18 rats in
      the HF/LC group were diabetic, whereas only 4 of 17 rats in the Control group
      were diabetic. The present results demonstrate that longterm feeding with a HF/LC
      diet decreases the secretion and sensitivity of insulin, and induces diabetes
      mellitus in rats. Furthermore, long-term feeding with such a diet may produce
      adverse effects on the blood plasma lipid profile, with elevated levels of
      triglycerides, nonesterified fatty acids, total cholesterol, and reduced levels
      of high density protein cholesterol in the plasma.

PMID- 14665712
TI  - The mRNA expression of insulin receptor isoforms (IR-A and IR-B) and IGFR-2 in
      the bovine corpus luteum during the estrous cycle, pregnancy, and induced
      luteolysis.
AB  - Isoform A of the human insulin receptor and the IGF-receptor type 2 (IGFR-2) are
      both receptors for insulin- like growth factor II (IGF II), which plays a major
      role in luteal development and function in bovine species. The objective of this
      study was to determine if both insulin receptor isoforms and IGFR-2 were
      expressed in the bovine corpus luteum (CL) and if they were regulated during the
      estrous cycle, pregnancy, and induced luteolysis. CL were collected at the
      slaughterhouse. For induced luteolysis, CL were obtained by transvaginal
      ovariectomy at 2, 4, 12, 48, and 64 h after prostaglandin (PG) F2alpha-injection.
      Real-time RT-PCR was applied to investigate mRNA expression. Two alternatively
      spliced transcripts encoding the insulin receptor were detected in bovine CL.
      These two isoforms corresponded to the known isoforms A (IR-A) and B (IR-B) in
      humans. IR-A mRNA predominated in bovine CL and was significantly down-regulated
      on d 5-7. IR-B mRNA was significantly up-regulated in the late luteal stage and
      during early pregnancy. IR-A showed a significant down-regulation at 48 h after
      PGF2. IGFR-2 mRNA was significantly up-regulated in mid and late luteal stages (d
      8-18). It is proposed that the differential mRNA expression of IR-A and IGFR-2,
      both binding IGF II, may play a role in the development and function of the
      bovine corpus luteum.

PMID- 14665713
TI  - Molecular assays to profile 10 estrogen receptor beta isoform mRNA copy numbers
      in ovary, breast, uterus, and bone tissues.
AB  - Estrogens regulate various biological processes in a diverse range of
      reproductive and nonreproductive tissues through two genetically distinct but
      structurally related high affinity nuclear receptors, the estrogen receptor alpha
      and beta (ERalpha and ERbeta). The physiological significance of the presence of
      two ERs that have redundant functions is not known. Several unique properties of
      ERbeta together with its distinct expression patterns are considered to be, in
      part, the basis for diverse functional actions of estrogens and opposing actions
      of selective estrogen receptor modulators (SERMs) in different tissues. To
      understand how relative expression levels of two ERs correlate to seemingly
      dissimilar actions of estrogens and SERMs, quantitative methods are required that
      can precisely measure the levels of every isoform. Previously, methods to
      quantify eight ERalpha isoforms have been described [Poola I. (2003) Anal.
      Biochem. 314, 217-226]. In this article, real-time PCRbased molecular assays are
      described that can distinguish and quantify as low as 100 copies of 10 ERbeta
      isoform mRNAs, the ERbeta1, ERbeta2, ERbeta4, ERbeta5, and ERbeta exon 2Delta,
      exon 3Delta, exon 4Delta, exon 5Delta, exon 6Delta, and exons 5-6Delta. Each
      isoform mRNA is quantified using a specific primer pair and a 5'FAM (carboxy
      fluorescein)- and 3'TAMARA (6-carboxy tetraethyl-rhodamine)-labeled probe and in
      comparison with a standard curve constructed with known copy numbers of its
      respective reverse transcribed cRNA. The devised assays were applied to profile
      10 ERbeta isoforms in four estrogen-sensitive tissues-ovary, breast, uterus, and
      bone. The sensitivity of detection of each isoform in these tissues varied from
      picograms to nanograms of reverse-transcribed total RNA depending on the isoform
      and the tissue. The results presented also show that each tissue has a distinct
      profile of 10 isoform mRNAs. Interestingly, ERalpha- negative breast cancer cell
      lines and tumors expressed significant amounts of ERbeta isoforms suggesting that
      mitogenic stimulation by estrogen exists in these tissues. Bone tissues expressed
      several isoforms, although wild type was not present. In addition to the assay
      development, evidence is presented to demonstrate for the first time that ERbeta4
      and ERbeta5 are full length receptors, contrary to previous reports that they are
      short receptors of exon 7-8.

PMID- 14665714
TI  - Alzheimer's disease: pathophysiological implications of measurement of plasma
      cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid
      receptors.
AB  - Alzheimer's disease is often characterized by an increase in plasma cortisol
      without clinical evidence of hypercorticism. Twenty-three consecutive patients
      with Alzheimer's disease and 23 age- and sex-matched healthy controls were
      studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS)
      (by enzyme immunoassay), the number of type I and type II corticosteroid
      receptors in mononuclear leukocytes (by radio-receptor-assay), and the lymphocyte
      subpopulations (by cytofluorimetry). Results are expressed in terms of median and
      range. In Alzheimer's disease, plasma cortisol was higher than in controls
      (median 0.74, range 0.47-1.21 vs 0.47, 0.36-0.77 mmol/L; p < 0.001). Plasma
      DHEAS, the DHEAS/cortisol ratio, and the number of type II corticosteroid
      receptors were significantly lower in AD than in controls (DHEAS: median 1.81,
      range 0.21-3.69 vs 3.51, 1.35-9.07 micromol/L; DHEAS/ cortisol: 2.04, range 0.3
      5.8 vs 6.8, range 2.7-24 and type II receptors: 1219, 1000-2700 vs 1950, 1035-
      2750 receptors per cell; p < 0.001). No correlation was found between the
      hormonal parameters, age, and mini-mental test score. These data support the
      hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer's
      disease, which is probably the consequence of damage to target tissues by
      corticosteroids.

PMID- 14665715
TI  - Tissue-specific regulation by estrogen of ezrin and ezrin/radixin/moesin-binding
      protein 50.
AB  - The morphology and function of rat GH3 pituitary cells are profoundly affected by
      estradiol-17beta (E2), presumably due to changes in the profile of gene
      expression. We recently reported that a major target of E2 in these cells is the
      ezrin gene, which encodes a cytoskeletal linker protein that forms a complex with
      ezrin/radixin/ moesin-binding protein 50 (EBP50) in some cell types. Other
      studies have shown that EBP50 levels are increased by E2 in human breast and
      uterine tissue. Thus, we examined whether ezrin and EBP50 expression is
      coordinately increased by E2 in GH3 cells in vitro and rat pituitary glands in
      vivo. Ezrin levels are repressed by the steroidal antiestrogen, ICI 182780, and
      this effect is abrogated by E2 and the ERalpha-specific agonist, PPT, in GH3
      cells. In contrast, EBP50 levels remained constant during these treatments. Ezrin
      and EBP50 did not display extensive colocalization. Moreover, ezrin was not co
      immunoprecipitated by an EBP50 antibody in parental GH3 cells or in GH3 cells
      stably overexpressing EBP50, but was co-immunoprecipitated with EBP50 in human
      breast MCF-7 cells. Disruption of the actin cytoskeleton of GH3 cells changed the
      distribution of ezrin within subcellular fractions, but had no effect on EBP50.
      Finally, in juvenile female rats, E2 injections increased ezrin expression in the
      pituitary and uterus, but increased EBP50 expression only in the uterus. These
      findings demonstrate tissue specificity in the formation of ezrin-EBP50 complexes
      and in the regulation of EBP50 expression in estrogen-responsive tissues.

PMID- 14665716
TI  - Variation in the expression of orexin and orexin receptors in the rat
      hypothalamus during the estrous cycle, pregnancy, parturition, and lactation.
AB  - The widespread distribution of mRNA encoding orexin- 1 (OX1R) and -2 receptors
      (OX2R) in the central nervous system suggests that orexin may be involved in
      multiple functional pathways. Central administration of orexin stimulates feeding
      and also affects ovarian steroid-dependent luteinizing hormone secretion,
      suggesting involvement of orexin in the regulation of reproductive function. To
      investigate a possible role for orexin in reproductive function, we examined
      variations in prepro-OX, OX1R, and OX2R mRNA levels in the female rat
      hypothalamus during the estrous cycle, pregnancy, parturition, and lactation
      using competitive reverse transcription-polymerase chain reaction. During the
      estrous cycle, only OX1R mRNA expression during late proestrus was significantly
      higher than that at metestrus. The prepro-OX and OX1R mRNA levels on d 1 of
      lactation were significantly higher than that during late pregnancy and
      lactation. Immunohistochemistry revealed the presence of orexin-A immunoreactive
      cells and the OX1R subtype in the lateral hypothalamic area as well as the
      magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei,
      respectively, in pregnant and lactating rats. These results suggest a role for
      orexin in reproduction that may be involved in regulating physiological function
      in early lactation through important binding sites in hypothalamic PVN and SON.

PMID- 14665717
TI  - Differential expression of GRK isoforms in nonmalignant and malignant human
      granulosa cells.
AB  - Granulosa cell tumors are serious ovarian neoplasms that can occur in women of
      all ages. While there have been numerous attempts to understand the cause of
      these malignancies, the pathogenesis of granulosa cell tumors (GCTs) still
      remains largely unknown. G-protein coupled receptor kinases (GRKs) are important
      regulators of signal transduction through the process of receptor desensitization
      and internalization. Receptors that are regulated by GRKs are members of the
      large family of seven-transmembrane receptors and include the follicle
      stimulating hormone receptor (FSHR). In granulosa cells, the FSH signaling system
      is responsible for cell proliferation, differentiation, and steroidogenesis. In
      the studies presented, we examined GRK mRNA and protein expression in
      nonmalignant human granulosa cells, in KGN cells, a human GCT cell line, and in a
      panel of human GCT samples. The KGN tumor cells express significantly less GRK4
      alpha/beta protein and higher levels of GRK2 and GRK4 gamma/delta protein as
      compared to nonmalignant human granulosa cells. In human GCT samples, GRK4
      alpha/beta protein was detected in 3 of the 13 tumor samples, whereas gamma/delta
      proteins expression was detected in all samples. These findings suggest that GRK
      protein expression is altered in GCTs and may be involved in the pathogenesis of
      these tumors.

PMID- 14665718
TI  - Chronic daily ethanol and withdrawal: 4. Long-term changes in plasma testosterone
      regulation, but no effect on GnRH gene expression or plasma LH concentrations.
AB  - Although ethanol has been repeatedly demonstrated to inhibit the hypothalamo
      pituitary-testes axis by multiple mechanisms, plasma testosterone levels can be
      normal in alcoholics who do not exhibit severely compromised liver function and
      even increased in some abstinent alcoholics, suggesting that adaptive changes to
      chronic alcohol abuse may alter these regulatory mechanisms. To address this
      variability, we have investigated the effects of chronic ethanol and withdrawal
      on rat testosterone regulation using a well-characterized liquid diet model that
      we have previously demonstrated to (1) provide daily oral ethanol consumption
      that produces behaviorally relevant plasma ethanol levels during the active
      (awake) stage of the photoperiod; (2) establish physical dependence on ethanol;
      and (3) produce not only hypothalamo-pituitary-adrenal axis, but also behavioral
      (anxiety-like behavior, response to novelty, sucrose preference) changes
      consistent with those of actively drinking and subsequently abstinent alcoholics.
      The results demonstrate that chronic daily episodes of ethanol consumption and
      withdrawal by male Sprague-Dawley rats decreased (p < 0.01) plasma testosterone
      levels late in the afternoon (by 70% relative to ad libitum-fed controls and 63%
      relative to pair-fed controls), but not in the morning. During gradual cessation
      of daily ethanol consumption, morning plasma testosterone levels increased, and
      this 90-115% (p < 0.05) increase was maintained for 3 d after complete cessation
      of ethanol consumption. Three weeks after cessation of ethanol consumption,
      plasma testosterone levels were again increased by approx 100% (p < 0.01). Plasma
      luteinizing hormone (LH) concentrations and anterior hypothalamus/preoptic area
      gonadotropin-releasing hormone (GnRH) mRNA levels were not altered at any of
      these time points. Thus, chronic daily ethanol consumption and daily withdrawal
      induced changes in circulating testosterone regulation that (a) were time of day
      dependent and (b) included adaptive changes persisting long after consumption of
      ethanol ceased. Accordingly, resolution of changes in testosterone regulation and
      their potential roles in alcohol abuse and relapse will require evaluating
      changes throughout the circadian cycle during, shortly after, and long after
      active alcohol abuse.

PMID- 14665719
TI  - Fluvastatin improves insulin resistance in nondiabetic dyslipidemic patients.
AB  - Statins have multiple actions, independent of their classical effects on
      lipoproteins. The data about the effects of statins on insulin resistance is
      controversial. This study was designed to search the statin effects on
      nondiabetic dyslipidemic patients. Thirty-five (17 male, 18 female) consecutive
      dyslipidemic patients 54.25 +/- 8.81 yr were enrolled in the study. After a
      standard follow-up period of lifestyle modification, the patients were given
      fluvastatin 40 mg/d for 8 wk. Serum analyses were done both before and after
      treatment. Insulin resistance was assessed by homeostasis assessment model
      (HOMA). Fasting plasma triglyceride, total and LDL cholesterol, fasting insulin,
      and HOMA index were significantly reduced and HDL cholesterol was improved after
      fluvastatin treatment. HOMA-IR was not correlated with triglycerides, LDL, HDL,
      or total cholesterol levels. The same situation was present for both fasting
      plasma insulin and fasting plasma glucose levels. Also age was not associated
      with HOMA-IR and fasting plasma insulin levels. As a conclusion, the present
      study indicates that fluvastatin treatment improves insulin resistance in
      dyslipidemic patients who do not have diabetes or impaired fasting glucose. Also,
      the effect of fluvastatin on insulin resistance is not associated with the
      lowering of triglycerides. The latter finding indicates that the effect of
      statins on insulin sensitivity may not be related with the lowering of
      triglycerides in dyslipidemic patients.

PMID- 14665720
TI  - High prevalence of thyroid ultrasonographic abnormalities in primary
      aldosteronism.
AB  - The study was performed to evaluate the prevalence of thyroid abnormalities
      detected by ultrasonography and, in particular, of multinodular nontoxic goiter
      in primary aldosteronism. We analyzed 80 consecutive of patients with primary
      hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic
      hyperaldosteronism) and 80 normotensive healthy controls, comparable for age,
      sex, iodine intake, and geographical area. Blood pressure, thyroid palpation,
      thyroid function, and ultrasonography were evaluated. The prevalence of
      ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27%
      in controls (p < 0.0001). There was a statistically significant difference in
      prevalence of these abnormalities in unilateral adenoma and idiopathic
      hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001,
      respectively). The prevalence of multinodular nontoxic goiter in idiopathic
      hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in
      female patients. From these data it seems to be worth considering the existence
      of primary hyperaldosteronism in patients with multinodular goiter and
      hypertension.

PMID- 14665721
TI  - Estrogen decreases chemokine levels in murine mammary tissue: implications for
      the regulatory role of MIP-1 alpha and MCP-1/JE in mammary tumor formation.
AB  - Estrogen contributes to the development of breast cancer through mechanisms that
      are not completely understood. Estrogen influences the function of immune
      effector cells, primarily through alterations in cytokine expression. Chemokines
      are proinflammatory cytokines that attract various immune cells to the site of
      tissue injury or inflammation, and activate many cell types, including T
      lymphocytes and monocytes. As an initial step toward ultimately determining
      whether regulation of chemokine expression and/or biological activity by estrogen
      could potentially be a contributing factor to the development and progression of
      mammary tumors, we evaluated the effect of estrogen on the expression of specific
      chemokines in murine mammary tissue. We also evaluated whether exposure of female
      mice to various chemokines could alter the growth of mammary tumors in the
      presence of estrogen. We report here that estrogen significantly decreases levels
      of the chemokines MIP-1alpha and MCP-1/JE in murine mammary tissue. Co-treatment
      with 4-hydroxytamoxifen partially reverses the suppressive effect of estrogen on
      MIP-1alpha levels. Estrogen increases the growth of CCL- 51 cell-based tumors in
      the mammary glands of female mice. Co-treatment with the chemokine MIP-1alpha or
      MCP- 1/JE substantially decreases the ability of estrogen to stimulate the
      formation of CCL-51 cell-based tumors. Our results show that estrogen might
      influence the bioactivity of specific chemokines through alteration of chemokine
      expression in mammary tissue, and further suggest that decreases in murine
      chemokines evoked by estrogen exposure could contribute to the promotion of
      mammary tumor growth.

PMID- 14665722
TI  - Calcium as a mediator of apoptosis in bovine oocytes and preimplantation embryos.
AB  - Cell death pathways and their regulation during development of the
      preimplantation embryo are poorly understood. Our previous studies indicate that
      Ca2+ is a key mediator of apoptosis in different cell models. We hypothesized
      that Ca2+ signaling mediates apoptotic cell death during early embryonic
      development via activation of Ca2+-dependent proteases, micro-calpain, and
      caspase-12. To test this hypothesis, established procedures for in vitro
      production of bovine embryos in concert with fluorescence, high-resolution,
      digital Ca2+ imaging, detection of Ca2+-dependent apoptotic mediators, and
      measurement of apoptotic cell death were used in the present studies. We found
      that an increase in intracellular free Ca2+ concentration ([Ca2+]i) in the
      individual embryo cells (2.6-fold) and mature oocytes (1.6-fold) was associated
      with activation of micro-calpain, induction of pan-caspase activity (5-10-fold),
      and expression of the Ca2+-dependent caspase-12. Inhibition of calpain or caspase
      activity significantly (1.5-2-fold) reduced apoptotic indices in embryos treated
      with the mobilizer of intracellular Ca2+ stores, thapsigargin, or the Ca2+
      ionophore, ionomycin. Taken together, these results support our hypothesis that
      Ca2+ is involved in apoptosis of the preimplantation bovine embryo and that Ca2+
      dependent apoptotic proteases are micro-calpain and caspase-12.

PMID- 14665723
TI  - Thyrotropin secretion during oral glucose tolerance test in acromegalic patients
      and control subjects.
AB  - It has been suggested that acute hyperglycemia stimulates somatostatin release
      from the hypothalamus, thus causing inhibition of growth hormone and thyrotropin
      secretion. Abnormal growth hormone secretory pattern to glucose load is
      characteristic of acromegaly, and it might reflect alterations in somatostatin
      release. We evaluated the sensitivity of serum thyrotropin response to presumed
      somatostatin inhibition during oral glucose tolerance test in 29 patients with
      active acromegaly, in 13 patients with inactive disease, and in 19 control
      persons suspected of impaired glucose tolerance. Both the acromegalic patients
      and the control subjects were euthyroid. Serum insulin, growth hormone,
      thyrotropin, free triiodthyronine, free thyroxine, and glucose were collected
      before and 30, 60, 90, and 120 min after the ingestion of 75 g glucose. While the
      free triiodthyronine and free thyroxine values did not change during the glucose
      test, the thyrotropin levels progressively and significantly declined in all
      groups. The basal to nadir thyrotropin ratio was higher in active acromegaly than
      in inactive disease and in control subjects (p < 0.01), suggesting that the
      glucose load inhibited thyrotropin stronger in active acromegalic patients. These
      data suggest that there is a possible strong somatostatin response to glucose
      load in acromegalic patients, which inhibits thyrotropin secretion. These data do
      not support the concept of decreased somatostatin drive in acromegaly.

PMID- 14665724
TI  - Hair zinc concentrations not subject to seasonal variation in adults in New
      Zealand.
AB  - The analysis of recently grown hair for zinc provides a biomarker of recent zinc
      status. Seasonal variation of zinc in hair has been demonstrated in children. The
      aim of this study was to investigate whether on a month-by- month basis there is
      a seasonal variation in hair zinc concentration in an apparently well-nourished
      adult population in New Zealand. It was hypothesized that increased hours of
      daylight would be associated with an increase in zinc concentration in hair.
      Thirty-four subjects (20 F, 14 M) aged 18-54 yr had occipital hair sampled at
      monthly intervals between June and December. Food variety was assessed by
      questionnaire. After thorough washing of the hair followed by nitric acid
      digestion, zinc was determined by flame atomic absorption spectrometry (FAAS)
      with special attention to the inclusion of blanks, internal and international
      standards, and reduction of contamination in each sample run. Analyses between
      two laboratories confirmed that two FAAS instruments were giving the same
      reading. No seasonal variation in hair zinc concentration was found. Reported
      dietary variety, ethnicity, gender, and hair color were unrelated to hair zinc
      concentrations in this population. This study adds to evidence that will help
      define the role of hair zinc in determining recent zinc status.

PMID- 14665725
TI  - Angiotensin-converting enzyme and metals in untreated essential hypertension.
AB  - Hypertension is an important health problem throughout the world and a risk
      factor for many diseases. Angiotensin-converting enzyme (ACE), a component of the
      renin-angiotensin system, has an important role in the regulation of blood
      pressure. Zinc (Zn), a trace element with important biological functions, is
      located in the catalytic site of ACE. Calcium (Ca), magnesium (Mg), sodium (Na),
      and potassium (K) also appear to be involved in hypertension pathogenesis. In
      this study, plasma ACE activities and Cat, Cai, Mg, Na, K, and plasma/erythrocyte
      Zn levels of 20 untreated patients with essential hypertension and 28 healthy
      individuals were evaluated. Plasma ACE activities (p<0.05) and erythrocyte Zn
      concentrations (p<0.001) were significantly higher in patients with essential
      hypertension than values of the control group. No significant difference was
      found between plasma Zn concentrations of the groups (p>0.05). Plasma Cat
      (p<0.001) and Mg levels (p<0.05) in essential hypertension were significantly
      lower than those of controls. Plasma Na, K, and Cai levels remained normal in
      essential hypertension. There are complex associations between metals and
      arterial pressure. Ca and Mg deficiencies seem to be associated with increased
      prevalence of hypertension. Increases in erythrocyte Zn may have a future
      potential use for diagnosis of hypertension.

PMID- 14665726
TI  - Different accumulation of elements in the rami of the coronary arteries of Thai.
AB  - To analyze the accumulation of elements in the rami of the coronary arteries, the
      authors determined element contents in both the coronary arteries and their rami
      of the Thai by inductively coupled plasma-atomic emission spectrometry. The
      subjects consisted of 13 men and 6 women, ranging in age from 34 to 83 yr. It was
      found that a higher accumulation of calcium and phosphorus occurred in the
      proximal sites of coronary arteries such as the anterior descending, right
      coronary, left coronary, and circumflex arteries than the distal sites such as
      the diagonal, lateral, conus, acute marginal, and posterior descending arteries.
      The accumulation of calcium and phosphorus in the anterior descending and right
      coronary arteries of the Thai increased remarkably in the fifties, thereafter
      decreased, and increased again in the eighties. It should be noted that a very
      high accumulation of calcium and phosphorus in the coronary arteries occurred in
      the fifties. In regard to relationships among the average contents of elements in
      the coronary arteries and their rami, it was found that there were very
      significant direct correlations between calcium and phosphorus contents, between
      calcium and magnesium contents, and between phosphorus and magnesium contents.
      These results suggested that as calcium and phosphorus increased in the coronary
      arteries and their rami, magnesium increased simultaneously in all of the
      coronary arteries and their rami.

PMID- 14665727
TI  - Fatty acids alter monolayer integrity, paracellular transport, and iron uptake
      and transport in Caco-2 cells.
AB  - The Caco-2 cell line was used as a model to determine if the type of fatty acid,
      unsaturated versus saturated, differentially altered the uptake and transport of
      iron in the human intestine and if the changes were the result of alterations in
      monolayer integrity and paracellular transport. Cells were cultured in either a
      lower-iron or normal-iron medium and incubated with a bovine serum albumin
      control, linoleate, oleate, palmatate, or stearate. Oleate, palmatate, and
      stearate enhanced (p < 0.05) iron uptake in cells grown in lower iron. The fatty
      acid effect on iron uptake by cells grown in normal iron was not as pronounced.
      Iron transport was not affected (p > 0.05) by an interaction between the type of
      medium (iron concentration) and the type of fatty acid. Iron transport was
      enhanced (p < 0.05) with palmatate and stearate. Various indicators of monolayer
      integrity and paracellular transport were also affected by the fatty acids, thus
      impacting iron uptake and transport. These results indicate that oleate,
      palmatate, and stearic can enhance iron uptake and transport; however, this
      enhancement may be the result of alterations in the integrity of the intestine.

PMID- 14665728
TI  - Effects of Ce(3+), Cd(2+), and Hg(2+) on activities and secondary structure of
      trypsin.
AB  - The different effects of Ce(3+), Cd(2+), and Hg(2+) on the activities and
      secondary structure of trypsin were studied. The results showed that trypsin
      activity was increased substantially by Ce(3+) in 0.5-5 micromol/L concentration,
      but the activity was decreased significantly by Cd(2+) or Hg(2+) in 0.5-5
      micromol/L concentration. The ultraviolet-visible spectrum of trypsin with 4
      micromol/L Ce3+ treatment was the same as that of the control, but the 232-nm
      characteristic peak of trypsin with 4 micromol/L Cd(2+) or Hg(2+) treatment was
      blue-shifted and the peak intensity weakened. The circular dichroism (CD)
      spectrum of trypsin with 4 micromol/L Ce(3+) treatment was similar to that of the
      control. The secondary structure of trypsin did not change with Ce(3+) treatment.
      However, the CD spectrum of trypsin with 4 micromol/L Cd(2+) or Hg(2+) treatment
      was different from that of the control and Ce(3+) treatment. The secondary
      structure of trypsin with Cd(2+) or Hg(2+) treatment changed greatly; for
      example, the alpha-helix and beta-sheet contents were reduced significantly, the
      beta-turn was enhanced greatly, and the random coil contents increased or
      decreased.

PMID- 14665729
TI  - A special comment on trace metals in the viscera of turbo marmoratus, a toxic
      snail, on Ryukyu Island.
AB  - Trace metals in the viscera of Turbo marmoratus, a huge conical spire, in the
      coral reef of Ryukyu Island were analyzed. The highest amount of Zn and Fe was
      detectable in the midgut gland known to be polluted by saxitoxin. This intestine
      maintained a considerable amount of Si (higher than Ca) which fluctuated in
      parallel with the taurine amount. These data suggest that the viscera of the
      alimentary tract accumulate some metals, especially Zn and Fe.

PMID- 14665730
TI  - Iodine and/or selenium deficiency alters tissue distribution pattern of other
      trace elements in rats.
AB  - Tissue distribution of Fe, Mn, Cu, and Zn, the essential trace elements
      associated with oxidant and/or antioxidant processes, was examined in iodine-
      and/or selenium-deficient rats (ID, SeD, ISeD). Fe and Mn were the most affected
      minerals in all types of deficiency states. Mn levels decreased significantly in
      the liver in all deficiency states (approx 20-30%), in the heart in ID and SeD
      rats (approx 30-35%) and in the testis in ID rats (approx 15%). Whereas Mn
      enhancement was noted in kidney (approx 45%) and plasma in SeD and ISeD (approx
      20% and 50%, respectively) animals. However, most striking alterations were seen
      with Fe. Significant elevation of Fe concentrations were observed in all
      deficiency states in the kidney (approx 90-125%) and heart (approx 20-25%), and
      in the liver in SeD (approx 35%) and ISeD (approx 75%) rats, whereas significant
      (approx 20%) Fe enhancement in the testis was observed only in ISeD animals.
      Lower Cu (approx 10-15%) and higher Zn (approx 10-20%) concentrations in heart
      tissues in all deficiency states were found; higher Zn (approx 20-35%) in the
      kidney of SeD and ISeD rats, and lower Cu in the testis of SeD animals were
      observed. In brain tissue, no alteration was seen in Fe, Mn, and Zn content,
      however, significantly increased (approx 15-20%) Cu concentrations were noted in
      all deficiency states. The results of this study indicated that iodine and/or
      selenium deficiency may modify the distribution and the homeostasis of other
      minerals.

PMID- 14665731
TI  - Effects of cerium on nitrogen metabolism of peach plantlet in vitro.
AB  - The effect of CeCl3 on the rooting and nitrogen metabolism of the peach plantlet
      in vitro was studied when the CeCl3 was added to the rooted medium. The results
      showed that the rooting rate and the fresh weight of roots could be increased and
      the length of root could be enlarged, and the activities of nitrate reductase,
      glutamine synthetase, glutamate dehydrogenase in the roots were increased
      significantly, the transformation of NO(3-) to NH(4+) and protein were promoted,
      and the nitrogen metabolism was accelerated when the plantlets grew in the
      optimum rooted medium that contained the concentration 0.3 micromol/L Ce(3+).

PMID- 14665732
TI  - Effect of Sm(3+) ion on growth of Bacillus thuringiensis by microcalorimetry.
AB  - By using an LKB-2277 Bioactivity Monitor, cycle-flow method, the thermogenic
      curves of aerobic growth for Bacillus thuringiensis cry II strain at 28 degrees C
      have been obtained. The metabolic thermogenic curves of B. thuringiensis cry II
      contained two distinct patterns: the first reflects the changes during the
      bacterial growth phase and the second corresponds to the sporulation phase. From
      these thermogenic curves in the absence and presence of Sm(3+) ions, the
      thermokinetic parameters such as the growth rate constants k, the interval time
      tau(I), the maximum power P (max 1) and heat-output Q(log) for log phase, the
      maximum power P (max 2) and heatoutput Q(stat) for stationary phase, the heat
      output Q(spor) for sporulation phase and total heat effects QT are calculated.
      Sm(3+) ion has promoting action on the growth of B. thuringiensis cry II in its
      lower concentration range; on the other hand, this ion has inhibitory action on
      the sporulation of B. thuringiensis in its higher concentration range. We also
      found that the effects of Sm(3+) ion on B. thuringiensis during the sporulation
      phase were far greater than that during the bacterial phase. It is concluded that
      the application of B. thuringiensis for controlling insecticides is not affected
      by the presence of the rare-earth elements in the environmental ecosystem.

PMID- 14665733
TI  - Fermentation process optimization of recombinant Saccharomyces cerevisiae for the
      production of human interferon-alpha2a.
AB  - The effects of different culture conditions on the expression level of human
      interferon-alpha2a (IFN-alpha2a) by using recombinant yeast were investigated in
      a 2.6-L jar fermentor. Appropriate supplement of glucose and the maintenance of
      residual glucose at a low level resulted in the reduction of ethanol formation
      and enhancement of the bioactivity of IFN-alpha2a to 4.9 x 106 from 3.1 x 10(6)
      IU/mL. When adenine was added evenly for 10-20 h of fermentation into the basal
      culture medium at a speed of 2 microg/mL of medium/h, OD600 was greatly increased
      to 24, and the protein increased to 276 mg/L. The content of ethanol generated
      was also reduced tremendously during the process, and as a result, 1.3 x 10(7)
      IU/mL of biologic activity was achieved. In the expression phase, pH had an
      important impact on expression level, which should be controlled at 5.5.

PMID- 14665734
TI  - Production of L-DOPA by tyrosinase immobilized on modified polystyrene.
AB  - Mushroom tyrosinase was immobilized on modified polystyrene- polyamino styrene
      (PSNH) and polymethylchloride styrene (PSCL)-to produce L-DOPA from L-tyrosine.
      Glutaraldehyde was used as an activating agent for the PSNH to immobilize the
      tyrosinase, and 10% (w/v) glutaraldehyde was optimal in conferring the highest
      specific activity (11.96 U/g) to the PSNH. Methylchloride on the PSCL was
      directly linked with the tyrosinase, and 1.5 mmol of Cl/g was optimal in
      attaining the specific activity of 17.0 U/g. The temperature and optimal acidity
      were, respectively, 60 degrees C and pH 5.5 for the PSNH, and 70 degrees C and pH
      3.0 for the PSCL. In a 50-mL batch reactor working over 36 h, the L-DOPA
      production rate at 30 degrees C was 1.44 mg/(L x h) for the PSNH and 2.33 mg/(L x
      h) for the PSCL. The production rate over 36 h was 3.86 mg/(L x h) for the PSNH
      at 60 degrees C and 5.54 mg/(L x h) for the PSCL at 70 degrees C. Both of the
      immobilized enzymes showed a remarkable stability with almost no change in
      activity after being stored wet. The operational stability study indicated a
      22.4% reduction in L-DOPA production for the PSNH and an 8.63% reduction for the
      PSCL over seven runs (each run was for 144 h at 30 degrees C) when the
      immobilized enzymes were used under turnover conditions. The immobilized
      tyrosinase was more stable on the PSCL than on the PSNH.

PMID- 14665735
TI  - Cloning, heterologous expression, and characterization of Thielavia terrestris
      glucoamylase.
AB  - Thielavia terrestris is a soil-borne thermophilic fungus whose molecular/
      cellular biology is poorly understood. Only a few genes have been cloned from the
      Thielavia genus. We detected an extracellular glucoamylase in culture filtrates
      of T. terrestris and cloned the corresponding glaA gene. The coding region
      contains five introns. Based on the amino acid sequence, the glucoamylase was 65%
      identical to Neurospora crassa glucoamylase. Sequence comparisons suggested that
      the enzyme belongs to the glycosyl hydrolase family 15. The T. terrestris glaA
      gene was expressed in Aspergillus oryzae under the control of an A. oryzae alpha
      amylase promoter and an Aspergillus niger glucoamylase terminator. The 75-kDa
      recombinant glucoamylase showed a specific activity of 2.8 micromol/(min x mg)
      with maltose as substrate. With maltotriose as a substrate, the enzyme had an
      optimum pH of 4.0 and an optimum temperature of 60 degrees C. The enzyme was
      stable at 60 degrees C for 30 min. The Km and kcat of the enzyme for maltotriose
      were determined at various pHs and temperatures. At 20 degrees C and pH 4.0, the
      enzyme had a Km of 0.33 +/- 0.07 mM and a kcat of (5.5 +/- 0.5) x 103 min(-1) for
      maltotriose. The temperature dependence of kcat/Km indicated an activation free
      energy of 2.8 kJ/mol across the range of 20-70 degrees C. Overall, the enzyme
      derived from the thermophilic fungus exhibited properties comparable with that of
      its homolog derived from mesophilic fungi.

PMID- 14665736
TI  - Novel laccase redox mediators: spectral, electrochemical, and kinetic properties.
AB  - The screening of potential redox mediators for laccase was performed using
      homogeneous enzyme preparations from Coriolus hirsutus and Coriolus zonatus. It
      was discovered that derivatives of 1-phenyl-3-methyl-pyrazolones were efficient
      substrates for the laccases. The characterization of two representatives of the 1
      phenyl-pyrazolone class, sodium 1-phenyl-3-methyl-4- methylamino-pyrazolone-5
      N(4)-methanesulfonate and 1-(3'-sulfophenyl)-3- methylpyrazolone-5, in the
      reaction catalyzed by laccase was carried out using spectral, electrochemical,
      and enzyme kinetics methods. The kinetic parameters for the oxidation of the
      newly discovered substrates were comparable with those for 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonate) (ABTS) oxidation by laccase. Electrochemical
      experiments demonstrated that oxidation of these compounds yielded two high
      potential intermediates capable of oxidizing veratryl alcohol, which was used as
      a lignin model substrate, to the corresponding aldehyde and acid. 1-(3'
      Sulfophenyl)-3- methylpyrazolone-5 was about 30-40% as effective in degrading
      veratryl alcohol compared to ABTS as judged from high-performance liquid
      chromatography kinetic studies. 1-Phenyl-3-methyl-pyrazolones may be of
      commercial interest for oxidoreductase-catalyzed biodegradation of organic
      compounds.

PMID- 14665737
TI  - Asymmetric reduction of benzil to (S)-benzoin with whole cells of Bacillus
      cereus.
AB  - Benzil (1) was selectively reduced to (S)-benzoin (2) in the presence of a wild
      type Bacillus cereus Tim-r01. A 92% yield of 2 with 94% enantiomeric excess ratio
      was attained in phosphate-buffered saline (PBS) (pH 7.5) by using glucose as a
      nutrient at 37 degrees C for 12 h. Compound 2 was not reduced further to
      hydrobenzoin (3) at all. The reduction activity differed greatly depending on the
      strain of B. cereus. Under these conditions the B. cereus strains IFO3001,
      IFO15305, IAM1110, IAM1229, IAM1656, and IAM1729 gave 2 in yields ranging from 23
      to 46% and the configuration of 2 was (S)-form (7 to 86% ee).

PMID- 14665738
TI  - Iodixanol development of a laboratory-scale technique to monitor the persistence
      of Mycobacterium avium subsp. paratuberculosis in Cheddar cheese.
AB  - Mycobacterium avium subsp. paratuberculosis (Map) is a potential human pathogen
      known to be present in raw milk from infected dairy herds. Current pasteurisation
      regimes do not totally inactivate Map resulting in the possibility of viable
      cells being present in pasteurised milk used for Cheddar cheese production. A
      laboratory-based method, ensuring strict safety precautions, was developed to
      manufacture 800-g Cheddar blocks, experimentally contaminated
      (postpasteurisation) with two different strains of Map. The composition of the
      model Cheddar produced was consistent with commercial product. Syneresis of the
      cheese curd caused a 1 log10 concentration of Map numbers from milk to cheese for
      a strain isolated from pasteurised milk. The type strain NCTC 8578 did not show a
      similar concentration effect, but did however survive the Cheddar manufacturing
      process. A small percentage (<5%) of the Map load for each strain was recovered
      in the whey fraction during the process.

PMID- 14665739
TI  - Parent-adolescent conflict and its resolution in monogamous and polygamous
      Bedouin Arab families in southern Israel.
AB  - The purpose of this study was twofold: (1) to compare whether children from
      polygamous family structures significantly differ from children from monogamous
      family structures with regard to the frequency of parent-child conflict, and (2)
      whether children from these two structures employ different patterns of family
      conflict resolution. To address these questions, a random sample of 212 high
      school students (60.8% monogamous) completed a self-administered survey. The
      results of MANOVA show no significant differences (p > 0.05) between these two
      structures with regard to the frequency of parent-child conflict. The results
      also show similar conflict management styles between these two family structures
      within each of the following five domains (privacy, school and career, money
      spending, going out and leisure, and physical appearance). This study is unique
      in that it is the first empirical research to be conducted in the field of
      conflict resolution among youth and adolescents in polygamous marital structures
      and therefore, further investigation is needed to replicate these results
      utilizing different cross-cultural populations practicing polygamy.

PMID- 14665740
TI  - A case report of possible health benefits of extra virgin olive oil.
AB  - The literature on the chemical analysis of cooking oils suggests that the
      cholesterol-reducing effect may well be due to the antioxidant agents rather than
      unsaturated fats. Furthermore, antioxidant agents are present in extra virgin
      olive oil and not in olive oil. There is some evidence, based on studies using
      patients, to support such a supposition. In this paper, we present a case report
      on the possible health effects of changing from olive oil to extra virgin olive
      oil. The case report is intended to raise some relevant issues to stimulate a
      debate and more research in this area.

PMID- 14665741
TI  - Tamoxifen induces vasorelaxation via inhibition of mitogen-activated protein
      kinase in rat aortic smooth muscle.
AB  - The contribution of the mitogen-activated protein kinase (MAPK) pathway to the
      relaxation induced by tamoxifen, a synthetic non-steroidal anti-estrogen, was
      examined in rat vascular smooth muscle. Tamoxifen (0.1-300 microM) inhibited the
      contraction induced by endothelin-1 (ET-1, 3 nM) in aortic smooth muscle in a
      concentration-dependent manner. The inhibitory effect of tamoxifen was not
      attenuated by 10 microM ICI 182,780, a selective antagonist of estrogen
      receptors. In the Ca(2+) channel inhibitor verapamil (1 microM)-pretreated
      strips, tamoxifen also inhibited the contraction induced by ET-1. Both PD098059
      and SB203580, inhibitors of MAPK/extracellular signal-regulated kinase (ERK)
      kinase and p38 MAPK, respectively, inhibited ET-1-induced contraction in aortic
      smooth muscle. In Western blot analysis with anti-phosphorylated MAPK antibodies,
      ET-1 (3 nM) enhanced activities of both ERK1/2 and p38 MAPK in aortic muscle
      strips, which were not attenuated by the treatment with 4 mM EGTA. Tamoxifen (100
      microM) inhibited the activities of ERK1/2 and p38 MAPK induced by ET-1 without
      significant changes in the expression of these kinases. These results suggest
      that tamoxifen induces relaxation of rat vascular smooth muscle, and that this
      is, at least in part, mediated by the inhibition of the Ca(2+)-independent MAPK
      pathway.

PMID- 14665742
TI  - Detection of radiation-induced apoptosis using the comet assay.
AB  - The electrophoresis pattern of apoptotic cells detected by the comet assay has a
      characteristic small head and spread tail. This image has been referred to as an
      apoptotic comet, but it has not been previously proven to be apoptotic cells by
      any direct method. In order to identify this image obtained by the comet assay as
      corresponding to an apoptotic cell, the frequency of appearance of apoptosis was
      examined using CHO-K1 and L5178Y cells which were exposed to gamma irradiation.
      As a method for detecting apoptosis, the terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) assay was used. When the frequency of
      appearance of apoptotic cells following gamma irradiation was observed over a
      period of time, there was a significant increase in appearance of apoptosis when
      using the TUNEL assay. However, there was only a slight increase when using the
      comet assay. In order to verify the low frequency of appearance of apoptosis when
      using the comet assay, we attempted to use the TUNEL assay to stain the apoptotic
      comets detected in the comet assay. The apoptotic comets were TUNEL positive and
      the normal comets were TUNEL negative. This indicates that the apoptotic comets
      were formed from DNA fragments with 3'-hydroxy ends that are generated as cells
      undergo apoptosis. Therefore, it was understood that the characteristic pattern
      of apoptotic comets detected by the comet assay corresponds to cells undergoing
      apoptosis.

PMID- 14665743
TI  - Immunohistolocalization of carbonic anhydrase isozyme (CA-VI) in bovine mammary
      glands.
AB  - The localization of bovine carbonic anhydrase isozyme VI (CA-VI) was examined
      immunohistochemically in bovine mammary glands during early lactation period
      (after 2-3 days of postpartum) and dry period (at about 2 months preparturition
      in adults), and young calves (at 30 and 150 days after birth) using specific CA
      VI antiserum. The immunoreaction for anti-CA-VI antiserum was very weak in the
      mammary glands in young (prepubescent) calves. In dry period, CA-VI was also
      weakly expressed in secretory epithelial (acinar) and ductal cells. In contrast,
      the reaction was intense in mammary gland cells in early lactation period. Dot
      blotting analysis indicated that anti-CA-VI reacted positively to beastings and
      mature saliva, but weakly or not at all to milk during the dry period or calf
      saliva, respectively. The intense expression of CA-VI in the mammary glands in
      early lactation period might compensate for low levels of secretion from
      functionally and structurally immature salivary glands in young calves.

PMID- 14665744
TI  - In-vivo therapeutic efficacy trial with artemisinin derivative, buparvaquone and
      imidocarb dipropionate against Babesia equi infection in donkeys.
AB  - The therapeutic efficacy of imidocarb, artesunate, arteether, buparvaquone and
      arteether+buparvaquone combination was evaluated against Babesia equi of Indian
      origin in splenectomised donkeys with experimentally induced acute infection.
      Efficacies of these drugs were tested by administering each drug or drug
      combination to groups of donkeys (having three donkeys each group). One group of
      donkey was kept as untreated control for comparing the results. Parasitaemia,
      haematology (WBC, RBC, PCV, granulocytes and haemoglobin), biochemical parameters
      (SAST, SALT, alkaline phosphatase, albumin/globulin ratio) were monitored at
      regular intervals. Individually, arteether and buparvaquone were found to have no
      parasite clearing efficacy and the treated animals died within 5-6 days after
      showing high parasitaemia and clinical symptoms of the disease. However,
      artesunate treated animals were able to restrict the parasite multiplication but
      only during the treatment period. Animals treated with imidocarb and
      arteether+buparvaquone combination were able to clear the parasite from the blood
      circulation after 2-5 days post-treatment (PT). After 55-58 days PT,
      recrudescence of B. equi parasite was observed in both these groups and a mean
      survival period of 66 days and 69 days, respectively, was recorded in these
      groups. Results of haemato-biochemical parameters had shown that imidocarb had
      deleterious effect on the liver function while on the other hand
      arteether+buparvaquone combination was found to be safe. This limited study
      indicates that arteether+buparvaquone combination could be a better choice than
      imidocarb for treating B. equi infection, but further trials are required in
      detail.

PMID- 14665745
TI  - Geographical variation of skull morphology and its functional significances in
      the red-cheeked squirrel.
AB  - Skulls of the red-cheeked squirrel (Dremomys rufigenis) from various geographical
      locations: Malaysia (peninsular area), Vietnam (south district)-Laos, and
      Thailand (north district) were osteometrically examined. The skull size of the
      squirrels in the southern (Malaysia) population was fundamentally larger than
      that in the northern (Vietnam, Laos and Thailand) populations. The proportion
      indices indicated that the splanchnocranium was relatively longer in the Malaysia
      population, and that the interorbital space was narrower in Vietnam-Laos, and
      Thailand populations. We suggest that the long nose and laterally-oriented orbits
      in the skull may be better adapted for terrestrial-insectivorous life in the
      Malaysia population and the binocular sense facilitated by rostrally-oriented
      eyes contributes to the arboreal-fruit eating behavior in the two northern
      populations. The Malaysia population was clearly distinguished from the other
      populations by the principal component analysis. We suggest that the geographical
      barrier of the Isthmus of Kra influences the morphological variation of the skull
      among the squirrel populations.

PMID- 14665746
TI  - The effects of antipyretics on influenza virus encephalitis in mice and chicks.
AB  - To investigate the effect of antipyretics on the murine and poultry models of
      influenzal encephalitis, we injected large quantities of antipyretics,
      acetylsalicylic acid (aspirin) and dicrofenac sodium (voltaren). The effect of
      antipyretic treatment on the murine encephalitis model was unremarkable
      histologically and immunohistochemically. Whereas in chicks, CNS lesions
      consisting of perivascular cuffing and gliosis appeared only in those animals
      treated with the antipyretics and viral antigen was detected mainly in the nuclei
      of glial cells or vascular endothelia of voltaren-treated animals. We here
      demonstrate that antipyretic treatment aggravated the hematogenous spread of the
      influenza virus to the CNS in chicks, but did not affect the transneural
      infection in mice.

PMID- 14665747
TI  - Development of an efficient method for recovery of Puumala and Puumala-related
      viruses by inoculation of Mongolian gerbils.
AB  - Puumala (PUU) virus and PUU-related viruses are difficult to isolate in cell
      culture. To determine whether animal inoculation would be a better alternative
      for virus recovery, the Sotkamo strain of PUU virus was inoculated into several
      animal species. Newborn Mongolian gerbils (MGs), mice, and rats were infected
      with the Sotkamo strain by intracerebral (ic), intraperitoneal (ip), and
      subcutaneous (sc) inoculation. Antibodies to PUU appeared in MGs at 30 days post
      infection (dpi), and in mice and rats at 15 dpi. Interestingly, virus appeared at
      7 dpi in lung and brain of MGs inoculated via ic and ip routes. Virus was
      detected in all tested tissues of MGs at 15 dpi, with a peak level of 1.36 x 10
      (5) focus forming units (FFU)/g in brain tissue. The virus titer declined with
      the onset of the antibody response and became undetectable by 75 dpi, when the
      antibody titer reached the maximum level. The appearance of the virus in mice and
      rats was delayed as compared to MGs, and the virus titer was apparently lower, at
      approximately 4 to 8 x 10(3) FFU/g, at 15 dpi. In addition, lung homogenates of
      antibody-positive Clethrionomys (C.) rufocanus (captured in Tobetsu, Hokkaido,
      Japan) were inoculated into MGs by the ic route. PUU-related viral RNA was
      detected at 16 dpi in the brains of MG inoculated with the lung homogenate, and
      antibodies were detected at 45 dpi. These findings indicate that newborn MG
      inoculation is an efficient method to recover PUU and PUU-related viruses.

PMID- 14665748
TI  - Sodium iodoacetate-induced experimental osteoarthritis and associated pain model
      in rats.
AB  - Degenerative lesions were induced in the knee joint of Wistar rats by
      intraarticular injection of chondrocyte metabolism inhibitor mono-iodoacetate
      (MIA) at doses of 0, 0.3 or 3 mg/joint. Histopathological examination and the
      measurement of hind paw weight ratio as an index of joint pain by incapacitance
      tester were performed. Histological findings that are similar to those observed
      in human osteoarthritis (OA), such as disorganization of chondrocytes, erosion
      and fibrillation of cartilage surface, and subchondral bone exposure etc., were
      observed in a MIA-dose-dependent manner. Saflanin-O fast green staining revealed
      that marked diffuse reduction of proteoglycan in cartilage tissue of rats treated
      with MIA. The clinical scores of the joint pain were closely correlated to the
      grade of histological findings. We conclude that the present experimental model
      in combination with a novel dual channel weight averager would be very useful for
      the study of human OA, and could be applied for estimation of therapeutic effect
      of new anti-OA drugs.

PMID- 14665749
TI  - Protective effects of vaccination with bovine leukemia virus (BLV) Tax DNA
      against BLV infection in sheep.
AB  - A DNA vaccination trial was performed on sheep to determine whether vaccination
      with bovine leukemia virus (BLV) transactivator Tax DNA is effective against BLV
      infection. Immunization was carried out with cationic liposomes containing the
      Tax-expressing plasmid DNA and subsequently all sheep were challenged with BLV.
      BLV titers in peripheral blood mononuclear cell (PBMC) determined by syncytium
      formation assay and BLV provirus load detected by genomic PCR analysis showed
      higher levels of virus titers in control sheep than those in Tax-vaccinated
      sheep. Higher levels of IFN-gamma mRNA expression have been demonstrated in
      vaccinated sheep after the challenge. These results suggested that Th1 type
      immune response induced by Tax DNA vaccine inhibited BLV propagation in
      vaccinated sheep at the early phase of infection.

PMID- 14665750
TI  - Feline leptin: immunogenic and biological activities of the recombinant protein,
      and its measurement by ELISA.
AB  - Leptin is a protein synthesized and secreted primarily by adipose tissue. The
      blood leptin concentration is known to reflect body fat content in rodents,
      humans and dogs, and thereby is useful for quantitative assessment of obesity. In
      the present study, we produced recombinant feline leptin in Escherichia coli
      transfected with feline leptin cDNA we cloned previously. The recombinant feline
      leptin with a molecular weight of 16 kDa induced phosphorylation of the signal
      transducers and activators of transcription 3 (STAT3) protein in the cells
      expressing rat leptin receptor. The anti-feline leptin antibody raised in rabbits
      reacted well to feline and human leptin and less to rodents' leptin in Western
      blot analysis. Sandwich enzyme-linked immunosorbent assay (ELISA) was developed,
      using rabbit anti-feline leptin antibody and recombinant feline leptin as a
      standard. In this ELISA system, cross-reactivity to human, rat and mouse leptin
      was 30.7%, 69.5% and 66.6%, respectively. The plasma leptin levels of 24 healthy
      cats were in a range from 0.3 to 29.7 ng/ml with the mean +/- SEM of 4.5 +/- 1.3
      ng/ml, being positively proportional to body fat content. These results indicate
      that our ELISA system may be useful for assessment of obesity in cats.

PMID- 14665751
TI  - Some characteristics of vaginal prolapse in Nepali buffaloes.
AB  - Prolapse of vagina is one of the important maternal abnormalities during
      pregnancy in cattle and buffaloes. A field investigation was carried out on 26
      Murrah graded buffaloes to study clinical characteristics of vaginal prolapse in
      buffaloes in Nepal. Fifty-seven percent of the 26 buffaloes with vaginal prolapse
      were either heifers or in first lactation. Sixty-five percent of the cases were
      in seventh month of pregnancy or later. About three quarters of the cases
      occurred between June and October. Twelve cases (63%) of the 19 animals excluding
      7 heifers had a history of vaginal prolapse in previous gestations. A half of the
      buffaloes were showing prolapse of the vagina even when they were in standing
      position and showing moderate or vigorous straining. After the conventional
      treatments, twenty-three buffaloes retained the replaced vagina and calved
      normally. One animal aborted although the vagina was retained. Two buffaloes had
      severest degree of vaginal prolapse complicated with edema, injury and cyanosis,
      and they did not respond to the treatment. The two buffaloes had frequently
      recurrent prolapse and subsequently died. Early detection and prompt treatment
      may be imperative to control the vaginal prolapse in buffaloes.

PMID- 14665752
TI  - Cloning of full-length preproendothelin-2 cDNA and its expression in dog.
AB  - Endothelin-2 (ET2) is a member of the endothelin family of 21-amino acid peptides
      with vasoconstrictive activity. We report here the molecular cloning of the
      canine full-length cDNA of the precursor form of ET2, prepro-ET2 (PPET2), from
      intestinal tissue by means of reverse transcription-polymerase chain reaction (RT
      PCR) in conjunction with 5'- and 3'-rapid amplification of cDNA ends (RACE).
      Aside from the poly (A) tail the cDNA was found to be 1195 bp and included an
      open reading frame of 534 bp encoding a PPET2 polypeptide of 178 residues, in
      which the regions corresponding to bioactive mature ET2 peptide, an intermediate
      form big-ET2, and endothelin-like peptide are found. The organ distributions of
      PPET2 mRNA and a splicing variant were analyzed by RT-PCR. PPET2 transcript was
      detected in duodenum, colon, stomach, lung, liver, uterus, ovary, testis and
      kidney, but not in spleen. A splicing variant was found in none of the organs.
      Thus, based on the cloned cDNA sequence, we established a quantitative assay for
      dog PPET2 mRNA level using a real-time PCR system. Quantitative analysis by this
      method in various organs of the dog demonstrated that the dominant gene
      expression occurs in the intestine, with higher expression in large intestine
      than in small intestine.

PMID- 14665753
TI  - Impeded establishment of the infective stage of Trichinella in the intestinal
      mucosa of mice by passive transfer of an IgA monoclonal antibody.
AB  - Our previous study showed that the IgA monoclonal antibody (mAb) HUSM-Tb1 forms
      immunoprecipitates on the cuticular surface of infective larvae of Trichinella
      britovi, and that intraperitoneal injection of this mAb to mice 5 hr before
      challenge infection confers a high level of protection against intestinal T.
      britovi. The same treatment produced a similar effect in BALB/c mice inoculated
      orally with Trichinella pseudospiralis larvae, indicating that the effects may be
      seen upon most members of the genus Trichinella. Worms recovered from the
      intestinal mucosa at 1 hr after challenge infection with T. pseudospiralis was
      few in mice passively immunized with the mAb, whereas a substantial number of
      worms were recovered from the mucosa of control groups. These results suggest
      that the IgA mAb impedes establishment of infective Trichinella worms in the
      intestinal mucosa. Trichinella worms inoculated orally into BALB/c mice
      vaccinated with ultraviolet-irradiated muscle larvae 3 weeks earlier were
      expelled between days 4 and 7 after challenge infection. Although the mAb HUSM
      Tb1 originated from the mesenteric lymph node cells of mice vaccinated repeatedly
      with such irradiated larvae, IgA-mediated expulsion does not seem to play an
      important role in this vaccination model.

PMID- 14665754
TI  - A comparative pathological study on canine necrotizing meningoencephalitis and
      granulomatous meningoencephalomyelitis.
AB  - Canine necrotizing meningoencephalitis (NME) and granulomatous
      meningoencephalomyelitis (GME) were compared pathologically. Gross observation
      exhibited lateral ventricular dilation and discoloration, malacia and/or
      cavitation of the cerebrum in NME. On the contrary, gross changes were milder in
      GME, except for occasional visible granulomatous mass formation.
      Histopathologically, the lesions of NME were distributed predominantly in the
      cerebral cortex and various degrees of inflammatory and necrotic changes were
      observed according to clinical stages. Besides, microscopic lesions of GME were
      mainly distributed in the white matter of the cerebrum, cerebellum and brainstem,
      which are characterized by perivascular cuffing, multiple granulomas and
      leptomeningeal infiltrates. Although macrophages and lymphocytes were predominant
      in the inflammatory lesions of both disorders, macrophages in GME transformed
      into epithelioid cells and exhibited more massive infiltration. Although lectin
      RCA-1-reactive cells were numerous in both disorders, lysozyme immunoreactive
      cells in NME were fewer than that in GME. Parenchymal infiltration of MAC387
      positive cells was common in GME and limited in NME. The number of CD3-positive
      lymphocytes in the GME lesions tended to be greater than in NME, though the
      difference was not statistically significant. Morphological and
      immunohistochemical differences of the lesions, in particular, the
      characteristics of infiltrative macrophages may reflect these different
      pathogeneses of the two disorders.

PMID- 14665755
TI  - Comparison of enzyme activities in plasma and leukocytes in dairy and beef
      cattle.
AB  - Concentrations of plasma glucose, immunoreactive insulin (IRI) and free fatty
      acid (FFA) and activities of enzymes related to energy metabolism and lactate
      dehydrogenase (LDH) isoenzyme pattern in plasma and leukocytes were investigated
      in lactating Holstein cows (dairy cattle) and fattening Japanese Black Wagyu x
      Holstein steers (beef cattle). IRI concentrations and LDH and malate
      dehydrogenase (MDH) activities in the plasma of beef cattle were significantly
      higher than those in dairy cattle. The cytosolic ratio of MDH/LDH activity in the
      leukocytes of beef cattle was significantly higher than that of dairy cattle.
      These findings might be associated with the different energy metabolism between
      dairy and beef cattle.

PMID- 14665756
TI  - Clostridium perfringens type A myonecrosis in a horse in Korea.
AB  - Acute hemorrhagic myonecrosis accompanied by severe inter- and intrafascicular
      edema and hemorrhage of the right gluteal area was diagnosed in a 13-year-old
      male thoroughbred horse. Once the muscular and fascicular changes were subsided,
      the horse then developed acute respiratory problem. Histologically, the lung had
      diffuse severe hemorrhage with mild neutrophilic infiltration. The cause of death
      was acute respiratory failure that is believed to occur secondary to toxaemic
      event. Alpha and beta2 toxin secreting Clostiridum perfringens type A was
      isolated from the muscle and lung. The diagnosis was based on the light
      microscopic examination, bacterial toxinotyping and toxin genotyping from the
      muscular and pulmonary lesion. Also, susceptibility of the isolates to
      antimicrobial agents was determined.

PMID- 14665757
TI  - Necrotic hepatitis due to Clostridium perfringens infection in newly hatched
      broiler chicks.
AB  - Multiple necrotic hepatitis lesions of 5 newly hatched broiler chicks in three
      flocks derived from two hatcheries were examined pathologically. The livers were
      brittle, and multiple yellowish or green foci were scattered on the surface and
      cut surface. The main histological finding was well demarcated multi-focal
      necrosis in the liver. Many Gram-positive large bacilli that reacted positively
      with polyclonal anti-Clostridium perfringens serum were observed in necrotic
      areas.

PMID- 14665758
TI  - Molecular clonings and sequences of Djungarian (Phodopus sungorus) and Chinese
      (Cricetulus griseus) hamster interferon-gammas.
AB  - Djungarian (Phodopus sungorus) and Chinese (Cricetulus griseus) hamster IFN-gamma
      genes were cloned and sequenced. The Djungarian and Chinese hamster genes were
      both 525bp nucleotides, resulting in 174 amino acids in full length with a
      predicted molecular weight (MW) of 19,560 dal and 19,775 dal, respectively. The
      first 23 amino terminal amino acids consisted of a hydrophobic signal sequence
      when cleavaged, which would result in a mature 151 amino acid polypeptide with a
      predicted MW of 17,115 dal in the Djungarian hamster IFN-gamma and 17,255 dal in
      the Chinese hamster one.

PMID- 14665759
TI  - Differences in Ibaraki virus RNA segment 3 sequences from three epidemics.
AB  - Phylogenetic tree and partial nucleotide sequence analysis of RNA segment 3 were
      conducted to compare the Ibaraki virus (IBAV) strains from three epidemics in
      Japan, and serotype 2 epizootic hemorrhagic disease virus strains isolated in
      Australia, Taiwan, and Canada. Each strain was classified relative to the Ibaraki
      disease (IBAD) epidemics, which occurred in 1959-1960, 1987, or 1997-1998. In
      particular, major variation of the gene was identified in the strains isolated
      after 1997 when a new type of IBAD with the abnormal birth was confirmed. Ibaraki
      viruses isolated in Japan were more closely related to Taiwanese and Australian
      strains based on genetics, while the Canadian strain was more distantly related.

PMID- 14665760
TI  - Acquired mitral stenosis in a cat with hypertrophic cardiomyopathy.
AB  - A seven-year-old castrated male domestic shorthair cat was diagnosed with
      hypertrophic cardiomyopathy (HCM) and suspected mitral stenosis (MS) based on
      electrocardiography, thoracic radiographs and echocardiographic findings. Post
      mortem examination of the heart revealed morphological features consistent with
      HCM. In addition, there was marked fibrous deposition on the surfaces of the
      chordae tendineae extending to both mitral valve leaflets, which caused total
      chordal fusion into pillars of fibrous tissue and fusion of the commissures. The
      present case indicates that acquired MS can occur in association with HCM in the
      cat.

PMID- 14665761
TI  - Successful treatment by percutaneous transvenous coil embolization in a small
      breed dog with intrahepatic portosystemic shunt.
AB  - A Miniature Dachshund, 3-month-old, 3.1 kg, was diagnosed as an intrahepatic
      portosystemic shunt (PSS) with the shunting vessel in 6-mm diameter. Percutaneous
      transvenous coil embolization (PTCE) was performed with a stainless steel coil in
      8-mm diameter. Intraoperative portal pressure elevated about 2.5 times after one
      stage coil occlusion. Two weeks after the PTCE, serum bile acid levels reduced
      within the normal range. The portogram showed complete occlusion of the shunting
      vessel 4 months after the PTCE. Approximately 3 years after the PTCE, the patient
      has shown no clinical signs. PTCE could be performed more easily and less
      invasively in a small-breed dog. It is therefore suggested that PTCE is a
      promising therapeutic technique in canine intrahepatic PSS.

PMID- 14665762
TI  - Relationship between seminal plasma lactoferrin and gonadal function in horses.
AB  - Total 78 semen samples were obtained from 27 Thoroughbred stallions (aged 6 to 27
      years), and were subjected to quantification of lactoferrin (Lf) in seminal
      plasma and examination of the seminal properties. The seminal plasma Lf
      concentration varied from 21 to 689 microg/ml, with a mean value of 244 +/- 151
      microg/ml (S.D.). The seminal plasma Lf concentration and total seminal plasma Lf
      positively correlated with the sperm concentration (r=0.5938, P<0.001) and with
      the total sperm number (r=0.6959, P<0.001), respectively. There was no
      correlation between seminal plasma Lf and sperm motility. These results suggest
      that seminal plasma Lf reflects gonadal function.

PMID- 14665763
TI  - Late abdominal complaints after appendectomy--readmissions during long-term
      follow-up.
AB  - BACKGROUND/AIMS: The postoperative risk of small bowel obstruction is a
      recognized complication following appendectomy. Few studies have reconsidered the
      whole extent of abdominal complaints and problems following appendectomy. This
      study tries to evaluate the long-term outcome describing abdominal complaints
      requiring readmission following appendectomy. METHODS: A retrospective study of
      3,230 patients undergoing open appendectomy at a single center university
      hospital in Sweden between 1981 and 1996. Late (>30 days) readmissions were noted
      and the cause for readmission and need for surgical intervention were analyzed.
      RESULTS: Overall, late readmissions occurred in 2.94% during a median follow-up
      of 10 years after appendectomy. Females predominated among those readmitted, as
      did patients with complicated appendicitis or a 'normal' appendix. Nonspecific
      abdominal pain with no sign of small bowel obstruction caused almost half of the
      readmissions (45%). To a large extent this group consisted of females (76%).
      Small bowel obstruction was seen in 1.24% and was surgically treated in 0.68% of
      all appendectomies. Incisional hernias were also seen (0.4% of all
      appendectomies). CONCLUSION: The magnitude of readmissions due to abdominal
      complaints is more pronounced than previously reported with as many patients with
      signs of small bowel obstruction managed nonoperatively as surgically, and
      frequent readmissions due to nonspecific abdominal pain.

PMID- 14665764
TI  - Transthoracic ultrasound of lung and pleura in the diagnosis of pulmonary
      embolism: a novel non-invasive bedside approach.
AB  - The diagnosis of pulmonary embolism (PE) presents a considerable challenge and
      requires a high index of clinical suspicion from the attending physician. In
      addition, diagnosing PE may require the use of one or more direct and indirect
      diagnostic methods. Here, transthoracic sonography (TS) provides an alternative
      and attractive bedside approach which is based on (1) detecting alterations in
      the lung parenchyma, (2) involvement of the pleura and (3) peripheral perfusion
      characteristics associated with thromboembolism. Using a 5 MHz or 3.5 MHz convex
      scanner, occasionally supplemented by a 7.5 MHz linear scanner or colour-flow
      Doppler mode, the intercostal areas are systematically examined by TS. Most of
      the PE-related lesions are localised in the lower lobes of the lung and are often
      associated with an area of pleuritic chest pain. The characteristic sonographic
      findings of TS in PE are multiple, hypoechoic, pleural-based parenchymal lesions
      which adopt a wedge-shape. In addition, a central echo may occasionally be
      detectable within the lesion. Another regular sonographic feature is the
      involvement of the pleura manifesting as either localised effusion, basal
      effusion or both. However, several differential diagnoses such as pneumonia,
      bronchogenic carcinoma, metastases of extra-pulmonary malignancies, and simple
      pleurisy need to be excluded. Since localisation of PE-associated lesions may
      occasionally escape sonographic detection, an inconspicuous sonographic result
      does not fully exclude PE. As detection of PE-associated lesions using chest
      ultrasonography has a high specificity and sensitivity, can be rapidly performed,
      is widely available, non-invasive, cost-effective, and avoids transport of
      critically ill patients to the investigation site, the technique may prove a
      valuable tool in the diagnosis of PE at bedside facilitating immediate treatment
      decision. Further, because the method focuses on detection of peripheral lesions
      it complements other diagnostic techniques employed when PE is suspected.

PMID- 14665765
TI  - Pleural fluid polymorphonuclear elastase: cui bono?

PMID- 14665766
TI  - pO2 - Do we treat the right thing?

PMID- 14665767
TI  - COPD patients or "healthy smokers": is IL-8 synthesis and release the borderline?

PMID- 14665768
TI  - A glandular problem.

PMID- 14665769
TI  - Polymorphonuclear elastase in the early diagnosis of complicated pyogenic pleural
      effusions.
AB  - BACKGROUND: Polymorphonuclear elastase (PMN-E) is a neutrophilic marker that has
      been implicated in acute inflammatory responses. OBJECTIVES: To evaluate the
      accuracy of PMN-E in the diagnosis of complicated pyogenic effusions. PATIENTS
      AND METHOD: We studied 536 patients with pleural effusion of various etiologies.
      There were 125 pyogenic bacterial effusions (42 typical parapneumonic, 17
      borderline complicated parapneumonic and 66 complicated parapneumonic or
      empyema), 83 tuberculous, 91 malignant, 42 paramalignant, 95 transudates, 28
      miscellaneous and 72 effusions of unknown origin. Classic markers (pH, glucose,
      proteins, adenosine deaminase, LDH, leukocytes and differential count) and the
      PMN-E level were quantified in pleural fluid. The accuracy of PMN-E as an early
      marker in the diagnosis of complicated pyogenic infectious effusions was
      evaluated among pleural effusions that were not diagnosed with classic
      biochemical markers, radiological findings or Gram stain. Since results of
      pleural fluid culture and cytological examination are generally available after a
      48-hour delay, they were not included as early markers in the initial diagnosis
      of pleural effusions. RESULTS: Early diagnosis of complicated pyogenic bacterial
      effusions was achieved in only 48 of 66 cases with classic markers. Among those
      that were not diagnosed with these parameters, a pleural PMN-E value >3,500
      microg/l discriminated between complicated and noncomplicated pyogenic bacterial
      effusions with a sensitivity of 67% and a specificity of 97%. CONCLUSIONS: PMN-E
      is useful in the early diagnosis and management of complicated pyogenic
      infectious effusions, which may be delayed with classic markers.

PMID- 14665770
TI  - Fourteen-year trend of tuberculosis dynamics in the northwest of Turkey.
AB  - BACKGROUND: The incidence of tuberculosis (TB) in different countries as
      estimated by the World Health Organization (WHO) vary from 23/100,000 and less in
      industrialized countries, 191/100,000 in Africa and 237/100,000 in South East
      Asia. OBJECTIVES: The aim of this study was to analyze the dynamics of TB in the
      northwest of Turkey, between 1988 and 2001. METHODS: All pulmonary TB cases
      reported to the National Tuberculosis Center by local TB dispensaries during 1988
      2001 were analyzed. The number of new and relapsed TB cases were documented and
      classified according to age and type of TB (standard classification of TB
      patients according to disease type: pulmonary, new, smear positive; pulmonary,
      smear negative; relapse, and extrapulmonary). We recorded information about the
      prevalence of TB in different patient groups (patients with a contact history,
      patients who were detected in active community screening or passive case
      finding), TB trends in different age groups, type of TB, patients who had
      relapses, percentage of patients who were lost to follow-up. RESULTS: A total
      number of 288,996 patients were examined at Zonguldak Tuberculosis Dispensary
      between 1988 and 2001. Case notification rates of TB decreased over the study
      period. Respiratory TB was the most commonly encountered form of disease (>90%).
      The percentage of TB decreased in the 0- to 14-, 15- to 24-year-olds and
      increased in the 25- to 44- and 45- to 64-year-olds. CONCLUSION: Properly
      designed disease surveillance systems are critical for monitoring the TB trends
      so that each country can identify its own high-risk groups and target
      interventions to prevent, diagnose, and treat the disease.

PMID- 14665771
TI  - Overproduction of MUC5AC core protein in patients with diffuse panbronchiolitis.
AB  - BACKGROUND: The genetic identities of mucins secreted in the airways of patients
      with diffuse panbronchiolitis (DPB) have not been previously investigated,
      although hypersecretion is a common feature of this disease. OBJECTIVE: The
      purpose of this study was to determine the production of MUC5AC, a major core
      protein of mucin in airway secretion, and the effect of macrolide treatment on
      such production in patients with DPB. METHOD: We performed Western blot analysis
      for MUC5AC of bronchoalveolar lavage fluid patients. Cases consisted of four
      groups including patients with DPB, idiopathic pulmonary fibrosis (IPF), and
      sarcoidosis, and healthy volunteers. RESULTS: MUC5AC was detected in DPB patients
      but not in other groups. Macrolide treatment tended to inhibit such production in
      DPB patients. CONCLUSIONS: Our results suggest that overproduction of MUC5AC
      plays an important role in the pathogenesis of DPB.

PMID- 14665772
TI  - Increased lung uptake of technetium-99m hexamethylpropylene amine oxime in
      diffuse infiltrative lung disease.
AB  - BACKGROUND: Diffuse infiltrative lung disease (ILD) is a heterogeneous group of
      disorders which predominantly affect the lung parenchyma and spare the airway.
      OBJECTIVE: To assess pulmonary vascular endothelium damage in ILD, the lung
      uptake of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was
      determined. METHODS: In 20 ILD patients and 25 controls without ILD, the lung
      uptake of 99mTc-HMPAO was measured. Anterior lung imaging, including a large part
      of the liver, was made 10 min after intravenous injection of 20-25 mCi of 99mTc
      HMPAO. Regions of interest covered the liver and lung to calculate the lung/liver
      uptake ratios. The 20 ILD patients included 10 patients with clinically manifest
      pulmonary disease (group 1) and 10 asymptomatic patients (group 2). All of the
      study subjects had normal pulmonary function test results. RESULTS: The mean
      lung/liver uptake ratio in the 25 controls without ILD (0.36 +/- 0.10) was
      significantly lower than that in the 20 ILD patients (0.97 +/- 0.61). In
      addition, the mean lung/liver uptake ratio in the 10 ILD patients with clinically
      manifest pulmonary disease (1.45 +/- 0.51) was higher than that of the other 10
      asymptomatic ILD patients (0.49 +/- 0.09). CONCLUSIONS: Our results indicated
      that determining the lung/liver uptake ratio on 99mTc-HMPAO lung imaging should
      be an objective method to assess subclinical pulmonary damage in ILD patients.

PMID- 14665773
TI  - Spirometry reference values for women and men aged 65-85 living in southern
      Europe: the effect of health outcomes.
AB  - BACKGROUND: Spirometry is more and more frequently used for the diagnosis of
      respiratory diseases in the elderly people. Unfortunately, reliable predictive
      values for the spirometric variables in the elderly are lacking. OBJECTIVES: Data
      obtained from 429 subjects participating in the multicenter Italian study SARA on
      respiratory health in the elderly were analyzed in order to derive reference
      values for spirometry in the age range of 65-85 years. The second aim of this
      study was to assess the influence of variables describing many dimensions of the
      health status on the prediction of spirometric variables in that age range.
      METHODS: Subjects were recruited as consecutive outpatients referred during the
      study period to 24 geriatric or respiratory institutions distributed throughout
      Italy. Spirometries were performed using the same equipment by specifically
      trained and certified personnel supervised by a real-time quality control
      program. In addition to the standard anthropometric variables, covariates
      describing the affective, mental, and general health conditions were investigated
      through standardized questionnaires, to improve the modeling of spirometric
      outcomes. RESULTS: Reliable predictive values for forced vital capacity (FVC) and
      forced expiratory volume in 1 s (FEV1) were produced (coefficient of
      determination, for FVC: R2 = 0.64; for FEV1: R2 = 0.54). The effect of general
      health conditions on spirometric outcomes accounted for the most part of the
      between-gender difference in the ageing-dependent decrease in lung function.
      CONCLUSIONS: We suggest that a multidimensional approach to health problems
      should be used for a better interpretation of spirometric results in the elderly.

PMID- 14665774
TI  - Abnormalities of the respiratory function and control of ventilation in patients
      with anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa is a good model to study the effects of malnutrition
      on the respiratory system, since it excludes the consequences that some chronic
      diseases can have on the lung. OBJECTIVE: The objective of this study was to
      assess pulmonary function and alterations in the respiratory system in patients
      with anorexia nervosa. METHODS: Twenty-two women, 12 with anorexia nervosa and 10
      healthy volunteers, were studied. Anthropometric data were gathered for all the
      participants. In every case, an arterial blood gas test and functional
      respiratory study, that included spirometry, plethysmography, measure of maximum
      muscular respiratory pressure and study of the ventilatory pattern at baseline
      and after hypercapnic stimulation, were performed. RESULTS: No significant
      differences were found in mean age and height in both groups of patients but
      there was a difference in body mass index (p < 0.05). In pulmonary function
      tests, an increase in residual volume (RV), RV/total lung capacity (TLC) ratio
      and functional residual capacity and a decrease in maximum respiratory pressure
      were found in patients with anorexia nervosa compared to the control group (p <
      0.05). Differences were also found in the ventilatory pattern, with a reduction
      in minute ventilation and occlusion pressure as well as a decreased response of
      these parameters to hypercapnic stimulation (p < 0.05) in the patients with
      anorexia nervosa. CONCLUSION: In patients with anorexia nervosa, a significant
      elevation in RV, in the RV/TLC ratio and in functional residual capacity and a
      decrease in the maximum respiratory pressure were noted. In addition, they
      present an alteration in the central respiratory drive and a response of the
      respiratory system to hypercapnic stimulation. Although these alterations have no
      repercussion on the maintenance of gas exchange in baseline conditions, they may
      have in extreme situations.

PMID- 14665775
TI  - Bronchial hyperresponsiveness and quality of life in asthmatics.
AB  - BACKGROUND: Quality of Life (QoL) measurements are more responsive to clinically
      significant changes that are not evaluated by conventional clinical measures.
      OBJECTIVE: The objective of this study is to examine the relationship between
      bronchial hyperresponsiveness (BHR) and QoL in asthmatic patients. PATIENTS AND
      METHODS: 394 patients underwent clinical follow-up, pulmonary function tests and
      the methacholine challenge test (MCHt), and completed the Asthma Quality of Life
      Questionnaire (AQLQ). RESULTS: 200 patients had a positive MCHt and in 194 it was
      negative. For all 32 items, asthmatic patients had a median value of 4.7 (4.2
      5.9) compared to 5.6 (4.7-6.3) in patients with negative MCHt (p < 0.01). For
      physical activities, patients with positive MCHt showed a median value of 5.0
      (4.5-6.0) compared to 5.7 (4.8-6.3) in patients with negative MCHt (p < 0.05).
      Median scores of 12 items of symptoms and 5 items of emotions were significantly
      lower in patients with positive MCHt [4.5 (3.7-5.8) and 5.1 (4.2-6.1)] than in
      patients with negative MCHt [5.5 (4.4-6.1) and 6.3 (5.2-6.9), respectively, (p <
      0.01)]. For items of environmental stimuli the median score was 4.7 (3.7-5.9) in
      patients with positive MCHt, being significantly lower than in patients with
      negative MCHt [5.4 (4.2-6.4), p < 0.05]. Patients with positive MCHt had lower
      values of QoL than patients with negative MCHt. CONCLUSIONS: QoL changes may be
      more sensitive than evaluation of BHR. The measurement of Qol may be important
      because it enables us to characterize patients who could be candidates eventually
      to a pharmacological treatment for BHR because they have an impaired QoL.

PMID- 14665776
TI  - Mediastinal lymph node staging by FDG-PET in patients with non-small cell lung
      cancer: analysis of false-positive FDG-PET findings.
AB  - BACKGROUND: Accurate staging of mediastinal and hilar lymph nodes is a critical
      factor determining operability in patients with non-small cell lung cancer
      (NSCLC). Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a
      tracer (FDG-PET) has recently been reported to be more effective in detecting
      tumor involvement in mediastinal and hilar lymph nodes than computed tomography
      (CT). OBJECTIVE: In this study, we analyzed the accuracy of FDG-PET in
      mediastinal and hilar lymph node staging in patients with NSCLC and the factors
      associated with false-positive or false-negative FDG-PET findings in mediastinal
      and hilar lymph node staging. METHODS: Fifty-four patients with NSCLC who
      underwent preoperative analysis including chest CT and whole-body FDG-PET were
      evaluated retrospectively. Using FDG-PET, lesions were considered to be positive
      if a definite, localized area of higher uptake, excluding physiologic uptake,
      than in surrounding normal tissue was present. On CT findings, lymph nodes were
      considered to be positive if they were >10 mm in short-axis diameter, except
      subcarinal lymph nodes (#7), which were considered to be positive if they were
      >15 mm in short-axis diameter. All patients underwent surgical resection of
      primary tumors and mediastinal and hilar lymph nodes between 1999 and 2001 in our
      institute. Resected lymph nodes were histologically examined for the existence of
      tumor cells. RESULTS: A total of 306 lymph nodes were resected and used for
      analysis. The sensitivity, specificity, positive predictive value and negative
      predictive value of FDG-PET were 73, 98, 70 and 98%, while those of CT were 55,
      96, 55 and 96%, respectively. When pre-operative nodal staging was compared with
      post-operative histopathological staging, 44 patients (81%) were correctly
      staged, 7 (13%) were overstaged and 3 (6%) were understaged by FDG-PET, while 39
      patients (72%) were correctly staged, 8 (15%) were overstaged and 7 (13%) were
      understaged by CT. All 7 overstaged patients by FDG-PET had other pulmonary
      complications, including interstitial pneumonitis (n = 2), previous pulmonary
      tuberculosis (n = 3), silicosis (n = 1) and emphysema (n = 1), although they were
      not in the active stage. In 3 understaged patients by FDG-PET, lymph nodes were
      also undetectable by CT. CONCLUSION: FDG-PET is superior to CT in mediastinal and
      hilar lymph node staging of patients with NSCLC. However, care should be taken in
      lymph node staging for patients who have other pulmonary complications, including
      interstitial pneumonitis, previous pulmonary tuberculosis and silicosis.

PMID- 14665777
TI  - Organizing pneumonia presenting as a solitary nodular shadow on a chest
      radiograph.
AB  - BACKGROUND: The role of infection as a cause of focal organizing pneumonia (OP)
      is not fully understood. OBJECTIVES: This study aimed to determine the clinical,
      radiological and pathological characteristics of patients with OP presenting a
      solitary nodular shadow on a chest radiograph. METHODS: Fourteen patients who
      presented with a solitary nodular shadow on a chest radiograph, pathologically
      diagnosed as OP after surgical resection, were allocated into two groups
      according to the histological findings. The first had OP with aggregates of
      neutrophils in airways and/or pulmonary parenchyma with or without necrosis or
      destruction of lung architecture (group 1: OP with neutrophilic infiltration; n =
      10). The second consisted of patients with OP presenting neither neutrophilic
      infiltration, necrosis nor destruction of lung architecture (group 2: OP without
      neutrophilic infiltration; n = 4). RESULTS: Cough, sputum, and chest pain were
      the common symptoms in both groups of patients. Computed tomography (CT) revealed
      that all nodules in both groups were located in the peripheral lung parenchyma
      and had irregular margins, and their shapes varied from round to wedge-shaped.
      Haemophilus influenzae was isolated from sputum or transbronchial aspirates from
      3 patients in group 1. CONCLUSIONS: The specimens resected from patients with
      focal OP mostly show small aggregates of neutrophils. However, the dominant
      histological feature is OP and neutrophilic infiltration, suggesting infection
      was a minor histological component in all cases. Clinical symptoms and chest CT
      findings did not clearly distinguish these two groups of patients. It is thus
      reasonable to place these OPs in the same category and to treat them in the same
      way. Surgical excision appears to be the only method for a precise diagnosis.

PMID- 14665778
TI  - Electromagnetic navigation during flexible bronchoscopy.
AB  - BACKGROUND: Flexible bronchoscopy is routinely utilized in the diagnosis and
      treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more
      invasive interventions, such as transthoracic needle aspiration, mediastinoscopy
      or even thoracotomy. Electromagnetic navigation is a novel technology that
      facilitates approaching peripheral lung lesions, which are difficult to sample by
      conventional means. The navigation system involves creating an electromagnetic
      field around the chest and localizing an endoscopic tool using a microsensor
      overlaid upon previously acquired CT images. OBJECTIVES: To determine the
      practicality, accuracy and safety of real-time electromagnetic navigation,
      coupled with previously acquired 3D CT images, in locating artificially created
      peripheral lung lesions in a swine model. METHODS: Peripheral lung lesions were
      created in four swine models by insertion of a metal tube (1 x 10 mm) via a
      transthoracic approach. An electromagnetic field was created by placing the
      animal on an electromagnetic location board. A position sensor incorporated into
      the distal tip of a dedicated tool was used to navigate to the various target
      lesions. Information gathered in real time during bronchoscopy was presented on a
      monitor simultaneously by displaying previously acquired CT images. Upon reaching
      the target lesion, biopsies were performed and the functionality and safety of
      the superDimension/Bronchus System was observed and documented. RESULTS: The
      registration accuracy expressed by the fiducial target registration error,
      expressing both the registration quality and the stability of fiducial
      (registration) points, was 4.5 mm on average. No adverse effects, such as
      pneumothorax or internal bleeding, were encountered in any of the animals in this
      study. CONCLUSIONS: Real-time electromagnetic positioning technology coupled with
      previously acquired CT images is an accurate technology added to standard
      bronchoscopy to assist in reaching peripheral lung lesions and performing
      biopsies.

PMID- 14665779
TI  - Stability of glutathione in induced sputum: impact of freezing.
AB  - BACKGROUND: Oxidative stress has repeatedly been linked to the pathogenesis of
      pulmonary disorders like asthma and chronic obstructive pulmonary disease.
      Measuring glutathione (GSH) in induced sputum (IS) offers a noninvasive tool to
      study oxidative stress in airway diseases. OBJECTIVES: This study assessed the
      stability of GSH in sputum supernatant under varying conditions. METHODS: GSH in
      IS of 14 (7 healthy, 4 chronic obstructive pulmonary disease, 3 allergic
      rhinitis) nonsmoking subjects was quantified spectrophotometrically. The
      stability of GSH in supernatant was analyzed over 24 h under different ambient
      conditions (room temperature and cooling at 4 degrees C). Reproducibility of GSH
      measurements in immediately processed and frozen supernatant (+72 h) was
      expressed by intraclass correlation coefficient (R(i)) and coefficient of
      repeatability (CR). RESULTS: GSH recovery in supernatant decreased in a time- and
      temperature-dependent manner. Samples stored at 4 degrees C and room temperature
      showed a rapid decline of stability after 2 h. Mean GSH concentrations in IS
      after freezing (-20 degrees C) and thawing after 72 h were not significantly
      different from GSH values measured immediately after processing of the samples
      (immediate processing: 17.9 +/- 13.9 microM; 72 h freezing: 16.4 +/- 12.9 microM,
      p = 0.2). The reproducibility between immediately processed and frozen samples
      was excellent (R(i) = 0.97; CR = 5.7 microM). CONCLUSIONS: Storage of sputum
      supernatant at room temperature or 4 degrees C leads to a rapid decline of GSH
      recovery compared with baseline values. Immediate freezing of samples is a
      suitable and valid alternative to rapid processing and allows collection and
      shipment of samples for subsequent analysis.

PMID- 14665780
TI  - Pulmonary sequestration.

PMID- 14665781
TI  - Miliary tuberculosis as a cause of acute empyema.
AB  - Adult respiratory distress syndrome (ARDS) and sepsis are known, life-threatening
      complications of miliary tuberculosis. This report describes a patient with
      miliary tuberculosis who rapidly developed an acute tuberculous empyema. She had
      a fulminant course culminating in ARDS, sepsis and subsequent death. This case
      highlights the rare association of acute empyema with miliary tuberculosis.

PMID- 14665782
TI  - Pulmonary infection due to Mycobacterium szulgai.
AB  - A 75-year-old man was admitted with cough, purulent sputum, fatigue and weight
      loss of 10 kg of some months' duration. His chest radiograph showed poorly
      defined opacities in the right lung. Eleven years before admission an epidermoid
      carcinoma of the right lung had been diagnosed and a right bilobar resection had
      been performed. The patient remained asymptomatic for 8 years. Cultures of 4
      consecutive sputum samples were positive for mycobacteria that were identified as
      Mycobacterium szulgai by gas chromatography. A 6-month regimen of rifampin,
      isoniazid and pyrazinamide resulted in complete eradication of the mycobacterium.
      M. szulgai is an unusual pathogen in humans. In the English literature, only 35
      cases of pulmonary disease have been reported. Its clinical and radiological
      characteristics are similar to tuberculosis but in contrast to the rest of the
      non-tuberculous mycobacteria, M. szulgai has shown in vitro and in vivo
      susceptibility to most primary antituberculosis drugs.

PMID- 14665783
TI  - Three unusual cases where cardiopulmonary bypass was used in thoracic surgery.
AB  - Cardiopulmonary bypass (CPB) is a technique which is commonly performed without
      any problem in cardiac surgery. CPB can also be used in patients with a tumoral
      mass adherent to the great vessels, in patients with critically narrowed airway,
      if cross-table intubation of the distal trachea is not feasible and in patients
      necessitating re-do surgery with extensive adhesions because it allows extensive
      mobilization of the heart and great vessels without compromising their function.
      It also allowed the central pulmonary artery to be controlled without comprising
      oxygenation and complete resection of a tumor localized in the A-P window. Herein
      we report such patients operated with CPB without any problem.

PMID- 14665784
TI  - Acute respiratory distress syndrome induced by rifampicin with high levels of
      neutrophil and eosinophil products in bronchoalveolar lavage fluid.
AB  - We reported a case with acute respiratory distress syndrome (ARDS) caused by
      rifampicin during therapy for pulmonary tuberculosis. A high level of eosinophil
      cationic protein in bronchoalveolar lavage fluid (BALF) was detected as well as
      interleukin-8 and neutrophil elastase. Based on these results together with the
      positive result of the drug lymphocyte-stimulating test, we concluded that
      rifampicin was the causative drug leading to ARDS. Corticosteroid therapy
      resulted in clinical improvement and resolution of the pulmonary infiltrates on
      the chest radiograph without the recurrence of pulmonary tuberculosis.

PMID- 14665785
TI  - Multiple lung nodules in a woman with a history of melanoma.
AB  - A 61-year-old Caucasian female presented with a 6-week history of dry persistent
      cough. She had no shortness of breath, chest pain, fever, chills, or weight loss.
      She had been diagnosed with melanoma on the left thigh 6 months earlier. It was a
      spindle cell variant, Clark's grade III, with maximal thickness of 0.5 mm. At the
      time of diagnosis of melanoma, there was no evidence of metastasis on chest
      radiographs or computed tomography (CT) of the abdomen and pelvis. Treatment of
      her melanoma was limited to surgical excision with no subsequent radiation or
      chemotherapy. Other significant past medical history included hypertension,
      hypothyroidism, and bilateral breast augmentation. She had a 40 pack-year history
      of smoking.

PMID- 14665786
TI  - Pulmonary alveolar microlithiasis. World cases and review of the literature.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic disease with unknown
      etiology and pathogenesis. The present work updates the world literature on PAM
      up to the end of 2001 by means of a full review, including minor reports in local
      languages (not English). Excluding secondary cases, a total of 424 cases have
      been reported worldwide, 269 of which were sporadic and showed a prevalence of
      the male sex and 155 of which were familial cases and prevalently affected the
      female sex. The highest number of cases has been reported in Europe, followed by
      Asia, especially Asia Minor, while the single nations with the greatest number of
      reported cases are Turkey, then Italy and the USA. The salient clinical features
      of PAM as described in the literature are analyzed: family history, clinical
      course, association with other diseases, presence of calcification in other
      organs. In the first cases, reported in the 60s and 70s, diagnosis was primarily
      made at autopsy, whereas nowadays diagnostic investigation is made above all by
      transbronchial biopsy and bronchoalveolar lavage. Radiological imaging is
      sufficient in cases where other family members are known to be affected,
      diagnosed by means of invasive techniques. There is no known treatment to date,
      while lung transplantation is performed in the severest cases. A better knowledge
      of the epidemiological characteristics of this rare disease could help to
      diagnose a larger number of cases and to gain insight into its etiology and
      pathogenesis, which are still unknown.

PMID- 14665787
TI  - Reproducibility and reversibility of tidal forced expirations.

PMID- 14665789
TI  - Conflict of interest in psychopharmacology: can Dr. Jekyll still control Mr.
      Hyde?

PMID- 14665790
TI  - Reflections on relevance: Psychotherapy and Psychosomatics in 2003.

PMID- 14665791
TI  - Escitalopram: superior to citalopram or a chiral chimera?
AB  - BACKGROUND: Escitalopram is the active isomer of the antidepressant citalopram.
      In theory single-isomer drugs may be superior but few have been found to have
      clinically significant advantages. The manufacturer claims that escitalopram has
      more efficacy and a faster onset of effect than citalopram. The purpose of this
      study was to assess how far these claims are justified. METHODS: Relevant trial
      reports were requested from H. Lundbeck A/S and the Swedish drug regulatory
      authority. The trials consisted of a pooled analysis of 1,321 patients from one
      unpublished, one partly published and one published eight-week trial, as well as
      a 24-week trial with 357 patients published as a poster. The studies compared
      escitalopram with placebo and/or citalopram in outpatients aged or=18 years who
      met specified criteria for depression. The trials' quality was assessed with
      Moncrieff et al.'s quality assessment instrument and the results compared with
      the claims from the advertisements. RESULTS: The advertising claims are not
      justified because they are based on secondary outcomes, non-intention-to-treat
      analyses and arbitrarily defined subgroups. The subgroup results are
      inconsistent. Methodological flaws in the trials could account for the
      differences found. Even if the differences claimed were real they appear too
      small to justify higher prices. CONCLUSIONS: On the evidence available to us the
      manufacturer's claims of superiority for escitalopram over citalopram are
      unwarranted. The Swedish and Danish drug regulatory authorities reached similar
      conclusions. This highlights the need for wider dissemination of national
      authorities' statements to other countries affected by the European Union's
      mutual recognition procedure.

PMID- 14665792
TI  - A randomized clinical trial of the treatment effects of massage compared to
      relaxation tape recordings on diffuse long-term pain.
AB  - BACKGROUND: Long-term musculoskeletal pain is a common problem in primary health
      care settings that is difficult to treat. Two common treatments are mental
      relaxation and massage. Scientific studies show contradictory results.
      Furthermore, many studies lack long-term follow-up even though it is a chronic
      disorder. The purpose of this randomized clinical trial was to assess possible
      effects of massage as compared to listening to relaxation tapes in conditions of
      'diffuse' and long-term musculoskeletal pain. METHODS: 129 patients from primary
      health care suffering from long-term musculoskeletal pain were randomized to
      either a massage or mental relaxation group, and assessed before, during and
      after treatment. RESULTS: During treatment there was a significant improvement in
      the three main outcome measures: self-rated health, mental energy, and muscle
      pain only in the massage group as compared to the relaxation group. However, at
      the 3-month post-treatment follow-up, there was a significant worsening in the
      outcome measures (time x group effect p < 0.05) back to initial rating levels in
      the massage group as compared to no changes in the relaxation group. CONCLUSION:
      Massage, but not mental relaxation, is beneficial in attenuating diffuse
      musculoskeletal symptoms. Beneficial effects were registered only during
      treatment. This lack of long-term benefits could be due to the short treatment
      period or treatments such as these do not address the underlying causes of pain.
      Future studies of long-term pain should include longer treatment periods and post
      treatment follow-up. It might also be worthwhile assessing the long-term benefits
      from booster treatment after the initial intense treatment period.

PMID- 14665793
TI  - Predictors of change during long-term analytic group psychotherapy.
AB  - BACKGROUND: All studies on patient variables as predictors of outcome are on
      short-term groups. Therefore, we wanted to study predictors of outcome in an
      observational study of 69 out-patients treated in long-term, analytic group
      therapy (mean = 32.5 months). METHODS: Based on results from research on short
      term groups, we selected 6 predictor variables representing central domains
      (demographics, diagnosis, initial severity of disturbance, chronicity,
      expectancy, and treatment duration) and explored their relationship with 5
      outcome variables (Global Assessment of Functioning, Global Severity Index,
      Inventory of Interpersonal Problems-Circumplex, global improvement, and chief
      complaints) by multiple regression analyses. RESULTS: Treatment duration up to
      2.5 years was a strong positive predictor. Contrary to findings from many short
      term studies, the presence of personality disorder, chronicity, and high initial
      severity of symptoms were not associated with less favourable outcome.
      Furthermore, marital status was not a positive predictor, and expectancy of a
      better outcome was only positively related to 1 of the outcome variables. Highly
      tentative results from exploratory stepwise regression analyses indicated that
      interpersonal problems on the subscale of 'coldness' might also be a negative
      predictor in long-term therapy. CONCLUSIONS: The study indicates that predictors
      of outcome in long-term group therapy may be different from those found in short
      term therapy.

PMID- 14665795
TI  - Coping strategies of women with breast cancer: a comparison of patients with
      healthy and benign controls.
AB  - BACKGROUND: Cancer has an enormous impact on the patient, triggering fears of
      suffering, disability and death. Still, little research has been published which
      investigates the coping strategies adopted by cancer patients, when attempting to
      deal with their serious health threat. Moreover, it is often not clarified
      whether the selected coping strategies are used exclusively by cancer patients,
      or whether other groups of women facing benign breast diseases or having health
      worries regarding their breasts share similar coping strategies. This study
      attempts to identify those coping strategies that distinguish breast cancer
      patients from non-malignant controls. METHODS: A sample of 180 breast cancer
      patients was assessed on how it coped with health threats. The control group was
      composed of 268 women who were diagnosed as having either a benign disease or
      were disease free. The Ways of Coping Questionnaire was administered in order to
      record the frequency of the coping strategies used under the health conditions.
      Univariate analyses were conducted to compare mean scores in coping strategies
      among the diagnostic groups. Multivariate analyses were performed to identify
      those variables that distinguish one group from the other. RESULTS: Compared with
      women with benign breast disease and those who were disease free, breast cancer
      patients significantly infrequently exhibited attributions of blame to self,
      whereas they did not differ from controls in other ways of coping such as self
      isolation, passive acceptance, seeking social support, problem-focused coping,
      positive reappraisal, distancing, and wishful thinking. CONCLUSION: Our results
      may suggest that under the conditions of a cancer diagnosis, patients do not tend
      to assign responsibility on themselves and their character, since they possibly
      need to avoid guilt, low self-esteem, and social distance, and to maintain a
      potential to invest in the adjustment process.

PMID- 14665794
TI  - A method for rating charts to identify and classify patients with medically
      unexplained symptoms.
AB  - BACKGROUND: As part of conducting a randomized control trial (RCT) to treat
      chronically high utilizing patients with medically unexplained symptoms (MUS), we
      developed the chart rating method reported here to identify and classify MUS
      subjects. METHOD: Intended at this point only as a research tool, the method is
      comprehensive, uses explicit guidelines, and requires clinician raters. It
      distinguishes primary organic disease patients from those with primary MUS,
      quantifies medical comorbidities in primary MUS patients, and also distinguishes
      subgroups among MUS patients that we call somatization (resembles DSM-IV
      somatoform disorders) and minor acute illness (MAI) which differs from DSM-IV
      somatoform definitions. Scoring rules are used to generate the diagnoses above.
      The rules may be set according to the investigator's needs, from highly sensitive
      to highly specific. RESULTS: We found high levels of agreement with the gold
      standard for MUS vs. organic disease (97.6%) and among raters for the key
      individual chart elements rated (92-96%). The method identified 206 MUS subjects
      and the extent of their medical comorbidities for entry into a RCT. It also
      identified somatization and MAI; the latter supports the validity of this newly
      reported MAI syndrome. CONCLUSION: We concluded that this method offered research
      potential for identifying MUS patients, for quantifying their medical
      comorbidities, and for classifying MUS subgroups.

PMID- 14665796
TI  - A self-administered version of a brief measure of suffering: first aspects of
      validity.
AB  - BACKGROUND: Measuring the impact of illness is important for several reasons.
      Recently, a new instrument was introduced using a pictorial approach in measuring
      the perception of suffering caused by illness: the Pictorial Representation of
      Illness Measure (PRISM). The aim of the present study was to introduce a self
      administered version of PRISM and to provide some first data on its validity.
      METHOD: A postal survey was conducted in subjects with the chronic depigmentation
      disorder vitiligo. Participants were members of the German vitiligo association.
      The response rate was 60.6%. Data of 333 respondents completing the PRISM were
      used for analysis. Besides illness-related measures, psychological variables were
      assessed with the following instruments: Satisfaction with Life Scale (SWLS),
      five-item version of the Mental Health Inventory, adaptation of the Skindex-29, a
      quality-of-life measure for skin diseases. RESULTS: Only 2.9% did not fill in the
      PRISM. Self-illness separation correlated as predicted with some illness-related
      variables. The distance was significantly larger in subjects whose depigmentation
      was no longer spreading. Significant correlations were also found with mental
      health (0.50), satisfaction with life (-0.28), perceived impairment of outward
      appearance (-0.65), and the Skindex subscales 'emotions' (-0.66) and
      'functioning' (-0.67). CONCLUSION: Data suggest that PRISM can be self
      administered. Measures of convergent validity confirm the usefulness of the new
      measure.

PMID- 14665797
TI  - PRISM: Enmeshment of illness and self-schema.
AB  - BACKGROUND: The Pictorial Representation of Illness and Self Measure (PRISM) is a
      recently developed tool purported to assess burden of suffering due to illness.
      The nature of the PRISM task suggests a conceptual link to the illness self
      schema construct hypothesised to be present in some individuals with chronic
      illness. This study investigates the relationship between PRISM and schema as
      measured by cognitive bias. METHODS: 43 patients with systemic lupus
      erythematosus (SLE) completed an information-processing task involving
      endorsement of positive and negative illness words as descriptors of themselves,
      followed by free recall of the words. The outcome measures were endorsement and
      recall bias for negative illness words. Patients also completed the PRISM task
      and were assessed on other physical and psychological variables. RESULTS: PRISM
      did not correlate significantly with age, depression, functional impairment or
      disease activity. In a multiple regression analysis, only recall bias made an
      independent contribution to PRISM. CONCLUSIONS: Illness self-schema appears to
      play a significant role in determining the way in which SLE patients complete the
      PRISM task. This is discussed in light of a schema enmeshment model recently
      proposed in the cognitive bias literature.

PMID- 14665798
TI  - Effects of chronic hypogonadism on corticosterone secretion and cyclic AMP
      production in male rat adrenocortical cells.
AB  - AIM: To determine the secretion of corticosterone (CCS) both in vivo and in vitro
      during different intervals after orchidectomy in male rats. METHODS: Three- and
      12-month-old rats had been orchidectomized 0, 3, 6, or 9 months before
      decapitation. RESULTS: Orchidectomy increased the concentrations of plasma CCS,
      the basal release of CCS, and the adenosine 3', 5'-cyclic monophosphate (cAMP)
      production in rat zona fasciculata reticularis (ZFR) cells. The forskolin/3
      isobutyl-l-methylxanthine-stimulated releases of CCS and cAMP production by ZFR
      cells were higher in rats with chronic hypogonadism. The CCS release from ZFR
      cells of orchidectomized rat was not altered by 8-bromo-cAMP treatment.
      Orchidectomy enhanced the stimulatory effect of deoxycorticosterone on CCS
      release in ZFR cells. CONCLUSION: These results suggest that orchidectomy-related
      increases of CCS secretion in rats are associated with an increase of adenylate
      cyclase activity, cAMP generation, and 11-beta-hydroxylase activity in ZFR cells.

PMID- 14665799
TI  - Marketing of alcohol to young people: a comparison of the UK and Poland.
AB  - This paper takes an international perspective on the marketing of alcohol to
      young people by examining case studies of the marketing of alcohol in the UK and
      Poland. It is suggested that marketing is a powerful mechanism for attracting
      young consumers. The alcohol industry is an innovative industry able to use a
      wide variety of marketing tools to achieve success in the market-place. It is
      important to recognise that the marketing activities of the industry are becoming
      increasingly transnational and that policy response has to be equally
      transnational.

PMID- 14665800
TI  - The relation of a family history of alcoholism, obstetric complications and
      family environment to behavioral problems among 154 adolescents in Germany:
      results from the children of alcoholics study in Pomerania.
AB  - BACKGROUND: Behavioral problems in adolescence have been shown to be associated
      with the presence of a positive family history of alcoholism (FH+), obstetric
      complications (OCs), and negative parenting practices. METHOD: This study tested
      the relation of these factors to aggression/delinquency and attention problems in
      an untreated population sample of 154 adolescents in Pomerania. Furthermore, we
      evaluated the predictive strength of a FH+, OCs and negative parenting styles in
      a prospective subsample of 127 adolescents using a hierarchical regression
      analysis. RESULTS: Group comparisons between offspring with higher vs. lower
      values on aggression/delinquency revealed that only rejection by the parents was
      significantly more often reported by teenagers with higher measures on these
      behavioral problems. Offspring with higher values on attention problems had more
      OCs reported by the mother and also had more feelings of parental rejection
      compared to controls. The results of the hierarchical regression analysis showed
      that parental rejection was the only significant predictor for both
      aggression/delinquency, and attention problems measured 1 year after the initial
      assessment. CONCLUSION: We conclude that parental rejection is a major risk
      factor for both aggression/delinquency and attention problems. Reflecting the
      fact that these behavioral problems have been reported to be strongly associated
      with later substance misuse, the improvement of parenting practices should be
      considered in prevention and intervention programs.

PMID- 14665801
TI  - Alcohol consumption among middle-aged women: a population-based study of Swedish
      women. The Women's Health in Lund Area (WHILA) study.
AB  - From a total population of 10,766 Swedish 50- to 59-year-old women, 6,917 (64.2%)
      participated in the Women's Health in Lund Area (WHILA) study, and among them
      6,623 (95.7%) answered the questions on alcohol consumption. One out of 4 women
      (26.0%) consumed no alcohol in an ordinary week (non-drinkers), 57.4% consumed
      not more than 83 g alcohol, 12.5% consumed 84-167 g and 4.2% consumed 168 g or
      more. The weekly drinkers had a median consumption of 40.0 g alcohol (range 2.5
      1,036.0) and the main sort of alcohol was wine. Comparing the four drinking
      groups, most differences occurred between the non-drinking and the weekly
      drinking women. The non-drinkers had lower socio-demographic status, poorer
      health and more symptoms, especially physical symptoms. In a multivariate
      logistic regression analysis, most associations between non-drinking and lower
      socio-demographic status remained.

PMID- 14665802
TI  - Use of caffeine-based products and tobacco in relation to the consumption of
      alcohol. An examination of putative relationships in a group of alcoholics in
      Israel.
AB  - The relations between the intake of alcohol and that of caffeinated beverages, as
      well as cigarette smoking, was examined in a group of chronic alcoholics in an
      Israeli treatment center. When data from the total sample was analyzed,
      relationships between alcohol and caffeinated beverages intake and between
      alcohol intake and smoking were observed. Caffeine use and smoking were also
      related. In addition, a subgroup of subjects with a family history of alcoholism
      revealed correlations between alcohol and caffeine consumption, between alcohol
      intake and smoking, as well as caffeine use and smoking. Subjects without a
      family history of alcoholism also showed relationships between alcohol and
      caffeine use and smoking. However, coffee intake and tobacco use was not related
      in this subgroup. The relevance of the findings to previous reports concerning
      alcohol drinking and smoking as well as the intake of coffee appear to be
      consistent with a notion of interaction between these respective behaviors
      occurring at a behavioral level rather than a genetic one.

PMID- 14665803
TI  - Prevalence, characteristics, associated mental disorders and predictors of DSM-IV
      nicotine dependence.
AB  - OBJECTIVE: Focussing on ever-smokers and comparing nicotine-dependent with
      nondependent subjects, we examined the characteristics, associations of nicotine
      dependence with other mental disorders as well as predictors of nicotine
      dependence. Never-smokers were not included in the reference group of the
      nondependent subjects, but were analyzed as a third group. METHODS: Data of 1,636
      never-smokers and 2,437 ever-smokers (i.e. 1,520 current smokers, 917 former
      smokers) were taken from the German Transitions in Alcohol Consumption and
      Smoking Study. Assessments were made using the Composite International Diagnostic
      Interview. RESULTS: About a third of the ever-smokers met the criteria for
      nicotine dependence in some point in their lives. Nicotine-dependent smoking was
      significantly associated with various substance use disorders, affective
      disorders and anxiety disorders using nondependent smoking as a reference group.
      Comparing never-smokers and nondependent ever-smokers, significant associations
      were found for substance use disorders only. Smoking behavior variables, alcohol
      abuse or dependence and anxiety disorders but not sociodemographic variables and
      affective disorders were predictors for nicotine dependence. CONCLUSION: Nicotine
      dependent smoking is distinct from smoking alone and nicotine-dependent smokers
      are a characteristically different subgroup within the smoking population.

PMID- 14665804
TI  - Relationship between prescribing and risk of opiate overdose among drug users in
      and out of maintenance treatment.
AB  - Opiate users (n = 135) from southern England, Glasgow and Edinburgh were
      interviewed about opiate overdose (lifetime). Fifty-six percent had overdosed.
      The majority (66%) reported mixing opiates with at least one other drug (mainly
      alcohol and/or benzodiazepines) at their last overdose. Patients identified
      misjudgements of purity, mixing drugs and misjudgements of tolerance as causes of
      overdose. The sample was divided into groups: (1) 'no prescription', (2)
      prescribed 'diazepam only', (3) prescribed 'methadone only' and (4) prescribed
      'methadone + diazepam'. The 'methadone + diazepam' group reported more lifetime
      and deliberate overdoses, the 'methadone only' group were more likely to have
      used several drugs at the time of their last overdose and the 'no prescription'
      group to have used only heroin. Drug users' overdose risk may vary as a result of
      their prescribed and non-prescribed drug use. Interventions should be developed
      and tailored according to clients' needs and current use patterns.

PMID- 14665805
TI  - Dosage regimes in the prescription of heroin and other narcotics to chronic
      opioid addicts in Switzerland--Swiss national cohort study.
AB  - AIMS: Within the guidelines of the research programme on medical prescription of
      narcotics for opioid addicts (PROVE), heroin, morphine, and methadone were
      prescribed to heavily opioid addicted individuals in Switzerland since 1994. This
      contribution analyses the course of dose levels during the treatment period.
      DESIGN: Naturalistic description of consumed dosages per day and month. SETTING
      AND PARTICIPANTS: The study describes the dosages prescribed to all individuals
      who began outpatient treatment in the PROVE programme in Switzerland between 1994
      and 1996. MEASUREMENTS: Consumed amount of narcotics per day and the course of
      dosage of injectable heroin in different treatment regimes. FINDINGS: Heroin was
      the most frequently prescribed narcotic. Of all consumption days, heroin had been
      applied in 77% as injection and in 9% in a smokeable form. The mean daily dosage
      was 474 mg for intravenous application and 993 mg for the smokeable form. Second
      most frequent was the prescription of oral methadone, in most cases in
      combination with heroin. The mean amount of daily consumption of oral methadone
      was 53 mg. There were dosage differences between treatment regimes. During the
      course of treatment the mean dosage for injectable heroin per day decreased
      significantly and, depending on the treatment regime, almost linearly.
      CONCLUSIONS: The significance of heroin dosages in heroin-assisted therapy for
      treatment outcome should be further explored, especially in the light of the
      markedly higher dosages in Switzerland compared to the UK. During the treatment
      period, dosages did not increase but generally decreased, indicating no further
      increase in tolerance.

PMID- 14665806
TI  - The immediate retest in temporary threshold shift audiometry.

PMID- 14665807
TI  - Investing in healthy human capital.
AB  - Although the value of human capital is not captured on company balance sheets, it
      may account for about half of the gap between a company's market value and book
      value. Yet, many companies do not focus comparable scrutiny on human capital
      management as compared with other large assets, nor do they systematically
      measure its output (ie, productivity). Methods are emerging to enable employers
      to assess productivity losses, including absenteeism and presenteeism, and to
      understand the associated costs (ie, direct medical costs, total productivity
      loss). This will permit employers to assess the value of programs to enhance
      health and productivity. We contend that the effective workforce is probably
      decreased by 5% to 10% because of health problems. We believe that employers who
      increase their investments in healthy human capital now will emerge tomorrow as
      the companies leading the gains in US productivity.

PMID- 14665808
TI  - Occupational medicine and its moral discontents.

PMID- 14665809
TI  - Lost productive work time costs from health conditions in the United States:
      results from the American Productivity Audit.
AB  - The American Productivity Audit (APA) is a telephone survey of a random sample of
      28,902 U.S. workers designed to quantify the impact of health conditions on work.
      Lost productive time (LPT) was measured for personal and family health reasons
      and expressed in hours and dollars. Health-related LPT cost employers 225.8
      billion US dollars/year (1685 US dollars/employee per year); 71% is explained by
      reduced performance at work. Personal health LPT was 30% higher in females and
      twice as high in smokers (> or =1 pack/day) versus nonsmokers. Workers in high
      demand, low-control jobs had the lowest average LPT/week versus the highest LPT
      for those in low-demand, high-control jobs. Family health-related work absence
      accounted for 6% of all health-related LPT. Health-related LPT costs are
      substantial but largely invisible to employers. Costs vary significantly by
      worker characteristics, suggesting that intervention needs vary by specific
      subgroups.

PMID- 14665810
TI  - Reported exposures, stressors, and life events among Gulf War Registry veterans.
AB  - We investigated the association of 15 exposures, 10 stressors, and 18 life events
      with illness symptoms reported by 978 veterans who believe they suffer from Gulf
      War-related illnesses. A mail survey was completed by veterans (60% response
      rate) from the Gulf War Health Registry. Variables most associated with high
      symptom group membership were reported chemical/biologic warfare (CBW), concerns
      with infection and faulty equipment, feelings of mistrust in the military, and
      disability leading to work stoppage within 2 years after the war. These data
      suggest that belief in CBW exposure, and the experience of war stress and serious
      negative life events after the war, are important concomitants of Gulf War
      illness. Models seeking to explain Gulf War symptoms need to incorporate a range
      of exposure and psychosocial factors to fully account for important influences.

PMID- 14665811
TI  - Comorbid mental disorders account for the role impairment of commonly occurring
      chronic physical disorders: results from the National Comorbidity Survey.
AB  - Most health and work productivity studies have focused on individual conditions
      without considering comorbidity. We illustrate the implication of this neglect by
      examining the effects of comorbid mental disorders on role impairment (number of
      sickness absence and work cut-back days in the past month) among people with
      chronic physical disorders. A nationally representative household survey of 5877
      respondents assessed current mental and physical disorders and role impairments.
      Four physical disorders were sufficiently common to be studied: hypertension,
      arthritis, asthma, and ulcers. All 4 physical disorders were associated with
      significant role impairments in bivariate analyses. However, further analysis
      showed that these impairments were almost entirely confined to cases with
      comorbid mental disorders. Effectiveness trials in workplace samples are needed
      to evaluate the cost-effectiveness of treating comorbid mental disorders among
      workers with chronic physical disorders.

PMID- 14665812
TI  - Factor analysis of fatiguing syndrome in Gulf War era veterans: implications for
      etiology and pathogenesis.
AB  - This study used factor analysis to identify possible subgroups of symptoms of
      fatiguing syndrome (FS). Subjects were classified with FS according to the 1994
      modified Centers for Disease Control and Prevention criteria with the exception
      that the chronicity of excessive fatigue could not be documented. The cases
      consisted of 640 Gulf War veterans who met the criteria, whereas the control
      groups were composed of 5417 Gulf War and 6493 non-Gulf War veterans who did not
      meet the criteria and had none of the medical conditions that were exclusionary
      in the FS group. Factor analyses were performed separately in each group. Factor
      analysis revealed 6 subgroups: fatigue, pain, infectious, gastrointestinal,
      respiratory, and neurologic/mood/fatigue. Although the factors were similar for
      both groups, they were more differentiated in the FS group than in the control
      group as evidenced by interfactor correlations.

PMID- 14665813
TI  - Impact of OSHA final rule--recording hearing loss: an analysis of an industrial
      audiometric dataset.
AB  - The 2003 Occupational Safety and Health Administration (OSHA) Occupational Injury
      and Illness Recording and Reporting Final Rule changed the definition of
      recordable work-related hearing loss. We performed a study of the Alcoa Inc.
      audiometric database to evaluate the impact of this new rule. The 2003 rule
      increased the rate of potentially recordable hearing loss events from 0.2% to
      1.6% per year. A total of 68.6% of potentially recordable cases had American
      Academy of Audiology/American Medical Association (AAO/AMA) hearing impairment at
      the time of recordability. On average, recordable loss occurred after onset of
      impairment, whereas the non-age-corrected 10-dB standard threshold shift (STS)
      usually preceded impairment. The OSHA Final Rule will significantly increase
      recordable cases of occupational hearing loss. The new case definition is usually
      accompanied by AAO/AMA hearing impairment. Other, more sensitive metrics should
      therefore be used for early detection and prevention of hearing loss.

PMID- 14665814
TI  - Noise exposure and hearing loss in agriculture: a survey of farmers and farm
      workers in the Southland region of New Zealand.
AB  - Farmers are known to be exposed to intermittent intense noise from a variety of
      sources, but long-term exposure and the resulting risk of hearing loss have not
      been well characterized. We studied a cross-sectional random sample of farms on
      which agricultural workers completed an audiometric test and questionnaire, and
      performed noise dosimetry on a subsample. Sixty-five percent of farms and a total
      of 586 workers participated. Noise on the subsample of 60 farms lay in a range
      between 84.8 to 86.8 dB(A) and hearing losses were consistent with this level of
      exposure. Age, driving tractors without cabs, and working with metal were
      important risk factors. Reported compliance with hearing protection was higher
      than that actually observed. The majority of farmers have a moderate risk of
      hearing loss, but a significant minority is at high risk. Elimination and
      isolation of noise sources are the control methods of choice, and if residual
      hearing protection is required, compliance must be improved.

PMID- 14665815
TI  - Effects of occupational noise exposure on blood pressure.
AB  - We measured 24-hour ambulatory blood pressure and 16-hour noise exposure
      continuously for 20 automobile workers, and used linear mixed-effects regression
      models to estimate transient and sustained effects of noise exposure on blood
      pressure. The occupational noise levels of the high-exposure workers with 85 +/-
      8 dBA were significantly higher than those of the low-exposure workers with 59 +/
      4 dBA (P < 0.05). We found a significant difference of 16 +/- 6 mm Hg in sleep
      time systolic blood pressure (SBP) existed between 2 exposure groups, and a
      marginal increase of 1 mm Hg SBP per 1-dBA increase in occupational noise
      exposure at a 60-minute lag time during work (P = 0.07). Occupational noise
      exposure had both transient and sustained effects on workers' SBP.

PMID- 14665816
TI  - Mortality risk in a birth cohort of commuter air carrier and air taxi pilots.
AB  - Commuter and air taxi pilots have higher work-related death rates than most other
      occupational groups. In this longitudinal study, the authors examined the
      mortality in a cohort of 3263 commuter and air taxi pilots. With adjustment for
      age, proportional hazards modeling revealed that termination or downgrading of
      medical certificates during the 11-year follow-up was associated with a
      significantly increased risk of overall mortality (relative risk, 2.32; 95%
      confidence interval [CI] = 1.43-3.77). Relative to the general population with
      similar demographic characteristics, commuter air carrier and air taxi pilots had
      significantly lower overall mortality (standard mortality ratio [SMR], 0.36; 95%
      CI = 0.32-0.41) and mortality from cardiovascular diseases (SMR, 0.18, 95% CI =
      0.15-0.22), but considerably higher mortality from aviation crashes (SMR, 128.88;
      95% CI = 6.35-2624.36). The results indicate that the current medical
      certification system is effective in maintaining a healthy pilot workforce.

PMID- 14665817
TI  - Chronic medical conditions and work performance in the health and work
      performance questionnaire calibration surveys.
AB  - Associations between chronic conditions and work performance (absenteeism,
      presenteeism, and critical incidents) were studied in reservation agents,
      customer service representatives, executives, and railroad engineers. Conditions
      and work performance were assessed with the World Health Organization's Health
      and Work Performance Questionnaire. Analysis of covariance was used to estimate
      associations. More work performance was lost from presenteeism than absenteeism.
      However, chronic conditions more consistently had negative impacts on absenteeism
      than presenteeism. Conditions with significant effects included arthritis,
      asthma, chronic obstructive pulmonary disease-emphysema, depression, and chronic
      headaches. Arthritis had the largest aggregate effect on absenteeism
      presenteeism. Only depression affected both absenteeism-presenteeism and critical
      incidents. Some chronic conditions have substantial workplace effects. Disease
      management programs for these conditions might have a positive return on
      investment (ROI). Health and productivity tracking surveys are needed to evaluate
      ROI and provide quality assurance.

PMID- 14665818
TI  - Effective intervention with ergonomics, antivibration gloves, and medical
      surveillance to minimize hand-arm vibration hazards in the workplace.
AB  - Medical surveillance was used in the workplace to determine and monitor the level
      of hand-arm vibration syndrome (HAVS) and carpal tunnel syndrome (CTS) present in
      workers exposed to upper extremity vibration. Ergonomic intervention in the form
      of new tools with lower vibration levels and the use of International Standards
      Organizaiton (ISO) 10819 antivibration gloves were associated with a decrease in
      the pathologic findings and symptoms in these workers. Workers without such
      intervention were more likely to show progression of symptoms and findings. These
      findings suggest that ergonomic intervention can be effective in controlling the
      workplace hazard of tool vibration.

PMID- 14665819
TI  - A review of the cognitive and behavioral sequelae of Parkinson's disease:
      relationship to frontostriatal circuitry.
AB  - BACKGROUND: Parkinson's disease is a neurodegenerative hypokinetic movement
      disorder presenting with subcortical pathology and characterized by motor
      deficits. However, as is frequently reported in the literature, patients with
      Parkinson's disease can also exhibit cognitive and behavioral impairments. These
      impairments may be attributed to dysfunction of multiple systems associated with
      the disease process in Parkinson's disease that are not necessarily related to
      motor symptoms. In recent years, considerable attention has addressed the
      circuits connecting the frontal cortical regions and the basal ganglia (i.e.,
      frontostriatal circuits) and how they mediate cognition and behavior in humans.
      It has been suggested that these same circuits are disrupted in Parkinson's
      disease and may be responsible for the frontal/executive deficits predominantly
      reported in this patient population. OBJECTIVE: The current survey of the
      literature provides a critique and analysis of the neuropsychological profile of
      Parkinson's disease, including cognitive impairments, behavioral alterations, and
      emotional processing deficits. A special feature of this paper is to ascertain
      how frontostriatal circuitry might provide the substrate for the
      neuropsychological impairments exhibited in Parkinson's disease. In so doing,
      studies involving nonhuman subjects, neurologically healthy adults, brain
      lesioned individuals, and patients with Parkinson's disease are reviewed to
      provide a novel perspective in conceptualizing and categorizing the cognitive and
      behavioral sequelae concomitant to specific frontostriatal circuit dysfunction in
      Parkinson's disease. CONCLUSIONS: The current review suggests that the
      neuropsychological profile of Parkinson's disease, which predominantly reflects
      frontal/executive dysfunction, may be attributed to disruption of the
      frontostriatal circuitry. The information generated from this review can serve as
      a guide in the assessment of frontal/executive dysfunction in Parkinson's disease
      with suggestions for a clinical neuropsychological test battery.

PMID- 14665820
TI  - Distinctive neuropsychological patterns in frontotemporal dementia, semantic
      dementia, and Alzheimer disease.
AB  - OBJECTIVE: To assess the ability of a brief neuropsychological bedside screening
      battery to discriminate between Alzheimer disease, frontotemporal dementia, and
      semantic dementia. METHODS: Subjects were 21 patients with frontotemporal
      dementia, 14 patients with semantic dementia, and 30 patients with Alzheimer
      disease comparable in terms of Mini Mental Status Examination score, age, and
      education. Frontotemporal dementia and semantic dementia diagnoses were made
      clinically using the consensus criteria of Neary et al. 1 Subjects were
      administered a brief neuropsychological screening assessing episodic memory,
      working memory, executive function, naming, spatial ability, abstract reasoning,
      and calculations. RESULTS: Both the Alzheimer disease and semantic dementia
      groups were significantly impaired relative to the frontotemporal dementia group
      on verbal memory, whereas only the Alzheimer disease group was impaired on visual
      memory. Frontotemporal dementia patients performed significantly worse on
      backward digit span and made significantly more executive errors than Alzheimer
      disease and semantic dementia patients. Semantic dementia patients were more
      impaired than Alzheimer disease and frontotemporal dementia patients on
      confrontation naming. Discriminant function analyses identified the 5 most
      discriminating variables that correctly classified 89.2% of cases. CONCLUSIONS:
      Frontotemporal dementia, semantic dementia, and Alzheimer disease are associated
      with distinct neuropsychological profiles that classify these dementia syndromes
      with considerable success. The neuropsychological profiles highlight the
      distinctiveness between the 3 syndromes, are consistent with the known loci of
      neuropathology in these conditions, and can potentially serve as an adjunct to
      the current clinical criteria.

PMID- 14665821
TI  - Reduced hippocampal volume in alcohol and substance naive Vietnam combat veterans
      with posttraumatic stress disorder.
AB  - OBJECTIVE: This pilot study was undertaken to exclude the effects of alcohol and
      other substances on brain morphology in posttraumatic stress disorder.
      BACKGROUND: Posttraumatic stress disorder and alcohol use are among the
      conditions associated with decreased hippocampal volume. The possible confounding
      contribution of alcohol and other substances of abuse to decreased hippocampal
      volume in posttraumatic stress disorder has not been previously explored
      directly. METHOD: In this pilot study, magnetic resonance imaging scans of 4
      substance naive subjects with combat-related posttraumatic stress disorder and of
      4 controls were quantified. RESULTS: Bilateral hippocampal volumes were
      significantly smaller in posttraumatic stress disorder subjects. No significant
      differences were found between posttraumatic stress disorder subjects and the
      comparison group for total brain, gray and white matter, and ventricular volumes.
      CONCLUSIONS: These findings suggest that posttraumatic stress disorder in the
      absence of alcohol and other substance abuse may be associated with reduced
      hippocampal volume. The significance of reduced hippocampal volume in
      posttraumatic stress disorder is discussed.

PMID- 14665822
TI  - Correlates of generalized anxiety and panic attacks in dystonia and Parkinson
      disease.
AB  - OBJECTIVE: To determine prevalences of generalized anxiety, generalized anxiety
      disorder, panic attacks, and panic disorder in primary dystonia (n = 28) and
      Parkinson disease (n = 28) and to explore their clinical correlates. BACKGROUND:
      We previously identified increases in Diagnostic and Statistical Manual of Mental
      Disorders, third edition generalized anxiety in dystonia and panic attacks in
      Parkinson disease. METHOD: Structured Clinical Interview (SCID) ascertainment of
      Diagnostic and Statistical Manual of Mental Disorders, third edition, revised,
      disorders. RESULTS: Generalized anxiety disorder was more common in dystonia
      while panic disorder was more common in Parkinson disease (P = 0.0018).
      Generalized anxiety developed more commonly after dystonia onset (i.e., secondary
      generalized anxiety) while panic attacks developed more commonly after Parkinson
      disease onset (P = 0.0132). Specific life prevalences were: generalized anxiety
      disorder, 7 subjects (25.0%) in dystonia versus 0 subjects (0.0%) in Parkinson
      disease; generalized anxiety, 11 (39.3%) versus 0 (0.0%); panic disorder, 2
      (7.1%) versus 7 (25.0%); and panic attacks, 2 (7.1%) versus 9 (32.1%).
      Exploratory analysis in Parkinson disease indicated a relationship of panic
      disorder (P = 0.027) and secondary panic attacks (P = 0.0009) to motor block
      frequency. There were nonsignificant trends toward associations of secondary
      generalized anxiety with lower Mini Mental Status Examination scores (P = 0.058),
      and of secondary panic attacks with presence of a depressive disorder (P =
      0.077). Depressive comorbidity rates are also presented. CONCLUSIONS: These
      findings suggest relations of generalized anxiety with reduced pallidal
      inhibition of thalamofrontotemporal projections, and panic attacks with locus
      coeruleus dysfunction.

PMID- 14665823
TI  - Exacerbation of mania secondary to right temporal lobe astrocytoma in a bipolar
      patient previously stabilized on valproate.
AB  - OBJECTIVES: To investigate breakthrough mania secondary to a right temporal lobe
      neoplasm in a bipolar patient previously stabilized on sodium divalproex.
      BACKGROUND: Right hemispheric brain tumors involving the orbitofrontal or
      basotemporal cortex are a rare cause of secondary mania. In such cases, early
      neurologic signs may be difficult to distinguish from bipolar symptoms.
      Breakthrough mania secondary to brain neoplasm in a bipolar patient stabilized on
      medication is an extremely rare phenomena which has not been previously reported.
      METHOD: The clinical course of a bipolar subject stabilized on valproate who
      developed mania secondary to a right temporal lobe astrocytoma is described.
      Serial brain magnetic resonance imaging (MRI), baseline electroencephalogram
      (EEG), and neuropsychiatric evaluations were used to examine the relationship
      between the patient's brain mass and behavioral disturbances. RESULTS: Symptoms
      were those that accompanied prior episodes of mania. In addition, signs of
      temporal lobe dysfunction were evident including periods of detachment, deja vu
      experiences, and olfactory hallucinations. In the context of mania,
      depersonalization was initially attributed to bipolar symptoms. Only several
      months later, when olfactory hallucinations and alterations in consciousness
      became evident, was a temporal lobe lesion suspected. Neuropsychiatric
      abnormalities responded to a combination of surgical intervention, radiation
      therapy, and topiramate, however the tumor was advanced and invasive at diagnosis
      resulting in a poor prognosis. CONCLUSIONS: This case suggests that clinicians
      examining unexplained cases of breakthrough mania should be vigilant for early
      signs of temporal lobe dysfunction, which could aid in detecting treatable
      lesions.

PMID- 14665824
TI  - Union-management cooperation.

PMID- 14665825
TI  - Building nurse leader capacity.

PMID- 14665826
TI  - Decision-making model for nursing.

PMID- 14665827
TI  - Understanding the complexity of registered nurse work in acute care settings.
AB  - Nursing shortages and patient safety mandates require nursing managers and
      administrators to consider new ways of understanding the complexity of healthcare
      provider work in actual situations. The authors report findings from a study
      guided by an innovative research approach to explore factors affecting registered
      nurse performance during real work on acute care medical-surgical units. Our
      findings suggest beginning targets for interventions to improve patient safety,
      as well as recruitment and retention, through support for registered nurse work.

PMID- 14665828
TI  - Development of leadership competencies as a team.
AB  - Creating positive change to move a leadership team forward in a learning
      environment was a challenge for senior executives. The author describes an
      organized approach to leadership competency development for both nursing and
      nonnursing department directors and senior administrative staff members. The
      project was based on a 360-degree assessment group composite analysis and was
      implemented during a 12-month period. Prioritization of leadership development
      occurred as a result of this effort within the facility strategic plan, and
      intradepartmental communication dramatically improved.

PMID- 14665829
TI  - Evaluating clinical information systems.
AB  - As members of organizational committees to evaluate and select clinical
      information systems, nurse executives must identify a system that not only has
      the core functionality to support necessary changes in workflow and optimize
      nurse productivity and patient safety but that also is embraced by the nursing
      staff. There are specific features that nurse executives must demand to help
      nurses at the bedside reap the greatest benefit from the technology.

PMID- 14665830
TI  - Joy at work!: creating a positive workplace.
AB  - How can we regain a sense of joy through our work? Many nurses feel disconnected
      from their organizations, morale is plummeting, and employee mistrust and
      cynicism are growing. Reversing these trends is crucial in the face of current
      and future labor shortages. The author shares recent information on healthcare
      workers who experience joy through their work with implications for today's nurse
      leaders.

PMID- 14665831
TI  - A reflective model for organizational assessment and interventions.
AB  - A visionary academic medical center in Colombia, South America, engaged the
      Institute for Nursing Healthcare Leadership in a multifaceted project for the
      overall goal of strengthening the model of professional practice. The authors
      describe a reflective model for organizational assessment that steered the in
      depth assessment of the organization. The model combines the constructs of
      culture, theory, patterns, and phenomenon with an iterative process. The
      organizational reflection process is applied to assessing key nursing roles and
      the nursing care delivery system. Recommendations and interventions that emerged
      from the assessment are included.

PMID- 14665832
TI  - Lower limb (well leg) compartment syndrome after urological pelvic surgery.
AB  - PURPOSE: Well leg compartment syndrome (WLCS) is being seen more frequently as
      the complexity and duration of pelvic urological surgery increases, ie
      reconstruction/radical cancer surgery. The etiology of WLCS is multifactorial and
      prevention should form the mainstay of treatment. With significant morbidity and
      mortality, in particular lower limb morbidity secondary to fasciotomy wounds and
      long-term neurological sequelae, all urologists should be aware of this
      iatrogenic complication and how to prevent or treat it when it occurs. MATERIALS
      AND METHODS: A retrospective review of the world literature using MEDLINE was
      performed from 1966 to 2002, searching for lower limb compartment syndrome (well
      leg compartment syndrome), and its association with the lithotomy position and
      pelvic surgery. RESULTS: Although WLCS is not commonly reported in the urological
      literature, it has significant morbidity and mortality. The incidence of WLCS is
      probably under reported due to failed diagnosis or misdiagnosis. With increased
      awareness the incidence of this iatrogenic complication may be minimized or
      avoided altogether. CONCLUSIONS: Because the lithotomy position is one of the
      most common positions used in urology, it is mandatory for urologists to be
      familiar with the complications associated with it. If this complication is
      recognized early, prompt treatment decreases morbidity and mortality. Minimizing
      the risk of WLCS will leave urologists less open to litigation, which may follow
      this significant iatrogenic complication.

PMID- 14665833
TI  - Noninvasive techniques for the measurement of isovolumetric bladder pressure.
AB  - PURPOSE: A total of 184,000 prostatectomies were performed in the United States
      in 2000 for the relief of presumed bladder outlet obstruction. However, it has
      been reported that prostatectomy using current indications fails to bring about
      symptomatic improvement in approximately one-fourth of patients. Pressure flow
      studies are currently recognized as the gold standard for the diagnosis of
      bladder outlet obstruction. However, these studies are associated with a number
      of disadvantages. They are time consuming, invasive and expensive, and carry some
      morbidity for the patient. It has been suggested that the use of pressure flow
      studies should be mandatory before surgery. The invasive nature of this test
      limits its application, and a variety of noninvasive methods have been suggested
      to circumvent the need for conventional urodynamics. MATERIALS AND METHODS: We
      conducted a MEDLINE search of the published literature on the use of noninvasive
      techniques to measure bladder pressure. RESULTS: Two promising techniques involve
      the noninvasive measurement of isovolumetric detrusor pressure. The first of
      these methods uses an external condom catheter and the second an inflatable cuff
      around the penis. Both of these methods rely on the interruption of urinary flow
      and the measurement of the bladder pressure transmitted along the fluid column
      between bladder and site of urethral occlusion. An alternative strategy analyzes
      flow patterns following compression and release of the urethra during voiding.
      CONCLUSIONS: Of the methods reported the penile cuff, which is inflated during
      voiding, or the penile squeeze technique, which infers bladder pressure from flow
      patterns, would seem the most likely to be clinically useful. A noninvasive
      measure of bladder pressure, allied to a free flow rate, would give a useful
      adjunct to the assessment of men with lower urinary tract symptoms.

PMID- 14665834
TI  - The historical origins of interstitial cystitis.
AB  - PURPOSE: We identify early descriptions of interstitial cystitis and trace its
      evolution as a clinical entity during the 19th century. MATERIALS AND METHODS:
      Primary and secondary source documents relating to interstitial cystitis, bladder
      inflammation and bladder stones were reviewed. RESULTS: What is believed to be
      the earliest published record of interstitial cystitis appeared in an 1836
      textbook by the Philadelphia surgeon Joseph Parrish, who documented a syndrome of
      chronic frequency, urgency, dysuria and pelvic pain he called "tic doloureux of
      the bladder." Tic doloureux was a contemporaneous diagnosis used to describe
      painful, idiopathic disorders of nerves. Parrish attributed this term to his
      mentor, Dr. Phillip Syng Physick, who applied it to patients with severe lower
      urinary tract symptoms with no discernible etiology, with the most common
      etiology during the 19th century being bladder stones. A review of archival
      material from the Philadelphia College of Physicians indicates that by 1808
      Physick had developed a concept of bladder inflammation, a "bladder ulcer," that
      produced lower urinary tract symptoms in the absence of bladder stone.
      CONCLUSIONS: By 1808 Philip Syng Physick had described an inflammatory condition
      of the bladder producing the same lower urinary tract symptoms as a bladder
      stone. By 1836 he had expanded this concept to include a chronic frequency,
      urgency and pain syndrome occurring in the absence of demonstrable etiology. We
      propose that these are the earliest known descriptions of bladder inflammation
      and interstitial cystitis.

PMID- 14665835
TI  - An evaluation of the decreasing incidence of positive surgical margins in a large
      retropubic prostatectomy series.
AB  - PURPOSE: Positive surgical margins adversely affect biochemical recurrence-free
      survival after radical retropubic prostatectomy (RRP) for prostate cancer. We
      retrospectively reviewed a large series of men who underwent RRP at a single
      academic university urology program to define the change in the incidence of
      organ confined (OC) disease and positive surgical margin (SM+) during the last 2
      decades. MATERIALS AND METHODS: Between 1982 and 2001, 9,035 men underwent RRP
      for clinically localized prostate cancer (T1 to T3a) at a single institution. We
      compared the incidences of OC disease and SM+ in this population. RESULTS: An
      increasing proportion of men presented with OC disease over time. The incidence
      of SM+ in the overall RRP population decreased dramatically over time. However,
      in men with nonorgan confined disease (pT3), the proportion with SM+ was stable
      and consistently elevated (22.7% to 27.8%), after the initial decrease from the
      early 1980s (53%). CONCLUSIONS: Widespread early detection programs for prostate
      cancer resulted in a downward stage migration in men presenting with clinically
      localized prostate cancer at our institution during the last 2 decades. The
      decrease in the percentage of men with SM+ was due to the increasing number of
      men with organ confined disease. These results imply that the decrease in
      surgical margin rates in the overall RRP population is most likely due to stage
      migration and improved patient selection, rather than major improvements in
      surgical technique. The stable percentage of SM+ among men with pT3 disease
      dictates the need for continued evaluation of surgical technique and the need for
      effective adjuvant therapy.

PMID- 14665836
TI  - Computerized tomography with 3-dimensional reconstruction for the evaluation of
      renal size and arterial anatomy in the living kidney donor.
AB  - PURPOSE: Computerized tomography (CT) with 3-dimensional (3-D) reconstruction has
      gained acceptance as an imaging study to evaluate living renal donors. We report
      our experience with this technique in 199 consecutive patients to validate its
      predictions of arterial anatomy and kidney volumes. MATERIALS AND METHODS:
      Between January 1997 and March 2002, 199 living donor nephrectomies were
      performed at our institution using an open technique. During the operation
      arterial anatomy was recorded as well as kidney weight in 98 patients and
      displacement volume in 27. Each donor had been evaluated preoperatively by CT
      angiography with 3-D reconstruction. Arterial anatomy described by a staff
      radiologist was compared with intraoperative findings. CT estimated volumes were
      reported. Linear correlation graphs were generated to assess the reliability of
      CT volume predictions. RESULTS: The accuracy of CT angiography for predicting
      arterial anatomy was 90.5%. However, as the number of renal arteries increased,
      predictive accuracy decreased. The ability of CT to predict multiple arteries
      remained high with a positive predictive value of 95.2%. Calculated CT volume and
      kidney weight significantly correlated (0.654). However, the coefficient of
      variation index (how much average CT volume differed from measured intraoperative
      volume) was 17.8%. CONCLUSIONS: CT angiography with 3-D reconstruction accurately
      predicts arterial vasculature in more than 90% of patients and it can be used to
      compare renal volumes. However, accuracy decreases with multiple renal arteries
      and volume comparisons may be inaccurate when the difference in kidney volumes is
      within 17.8%.

PMID- 14665837
TI  - Contrast enhanced spiral computerized tomography in live kidney donors: a single
      session for anatomical and functional assessment.
AB  - PURPOSE: We evaluated contrast enhanced spiral computerized tomography (CT) as a
      single session for anatomical and functional assessment of potential live kidney
      donors. MATERIALS AND METHODS: The study included 80 consecutive kidney donors.
      In addition to routine donor evaluation, radiological imaging of the kidneys was
      performed with spiral CT, which was also used for selective determination of the
      glomerular filtration rate (GFR) of each kidney. All donors underwent 99mTc
      mercaptoacetyltriglycine renal scan as a gold standard for GFR determination.
      Anatomical results of spiral CT were compared to operative findings at donor
      nephrectomy. Moreover, the results of CT GFR were compared with those of standard
      99mTc-mercaptoacetyltriglycine GFR. RESULTS: Spiral CT detected major renal
      abnormalities that might be potentially significant for safe renal donation in 4
      of the 80 donors (5%). Spiral CT had 100% sensitivity, 85.7% specificity and
      97.2% overall accuracy for detecting the number of renal arteries. To identify
      the number of renal veins spiral CT had 100% sensitivity, 92.3% specificity and
      98.6% overall accuracy. A comparison between the isotope GFR of each kidney with
      the corresponding CT GFR showed a perfect correlation (r = 0.54, p <0.001). For
      the right and left kidneys mean isotope clearance was not significantly different
      from that of mean CT clearance. CONCLUSIONS: Multidetector row spiral CT with
      contrast medium can provide accurate information regarding the anatomy of the
      urinary tract and vasculature of the kidney. Moreover, it can detect renal and
      vascular abnormalities that might be potentially significant for safe renal
      donation. In addition, it can accurately demonstrate selective GFR of each
      kidney. Therefore, we recommend spiral CT with contrast material as a single
      radiological diagnostic modality for the assessment of potential live kidney
      donors.

PMID- 14665838
TI  - Clinical skills acquisition for hand-assisted laparoscopic donor nephrectomy.
AB  - PURPOSE: The learning curve associated with laparoscopic surgery may be
      associated with higher patient risk, and in the setting of kidney donation such
      risk may be unacceptable. We characterize the learning curve for hand-assisted
      laparoscopic donor nephrectomy in the context of a urology training program, and
      establish a case volume threshold after which improvements in laparoscopic skill
      can be demonstrated. MATERIALS AND METHODS: The study included 245 consecutive
      laparoscopic cases, including 111 donor nephrectomies, performed in 2 (1/2) years
      to characterize various measures of experience. Documentation of resident
      involvement in each case was made by a single surgeon and collected
      prospectively. Outcomes assessed included operative time, blood loss and
      intraoperative complications. RESULTS: Of the 111 hand-assisted donor
      nephrectomies the resident was surgeon in 47%. Operative time proved a reliable
      and sensitive measure of surgeon experience. Increasing laparoscopic experience,
      as measured by several parameters, was associated with decreasing operative time
      (each p <0.02). Measurable improvements in laparoscopic skill were realized after
      participating in 13 (p = 0.007) or serving as surgeon in as few as 6 (p = 0.02)
      hand-assisted donor nephrectomies. Conversion (2%) and intraoperative
      complication rates (3%) were low. CONCLUSIONS: Skills for hand-assisted
      laparoscopic donor nephrectomy can be safely taught in the context of a urology
      training program independent of resident training level. We documented measurable
      improvements in laparoscopic skill as gauged by operative time. Our findings
      provide a basis by which expectations can be set for laparoscopic skill
      acquisition in the context of a residency program and for the laparoscopically
      naive surgeon.

PMID- 14665839
TI  - Donor nephrectomy: A comparison of techniques and results of open, hand assisted
      and full laparoscopic nephrectomy.
AB  - PURPOSE: Laparoscopic donor nephrectomy (LAP) has been gaining more popularity
      among kidney donors and transplant surgeons. There have been some concerns about
      the function of kidney grafts harvested by laparoscopic procedures. We report our
      results of LAP. MATERIALS AND METHODS: Prospective data were collected for our
      donor nephrectomy operations. A telephone survey was done by an independent
      investigator on the impact of surgery on quality of life. Graft function was also
      evaluated by serial serum creatinine and mercaptoacetyltriglycine renal nuclear
      scans. RESULTS: A total of 100 patients were included in the study; of whom 55
      underwent open donor nephrectomy (OD), 28 underwent LAP and 17 underwent hand
      assisted donor nephrectomy (HAL). Mean patient age was 39 +/- 12 years and it was
      similar in all groups. Mean operative time was 306 +/- 40 minutes for LAP, 294 +/
      42 minutes for HAL and 163 +/- 24 minutes for OD (p = 0.001). Laparoscopic
      operative time was decreased to 180 +/- 56 minutes for LAP and 155 +/- 40 minutes
      for HAL in the last 10 patients. Mean estimated blood loss was 200 +/- 107 cc for
      LAP, 167 +/- 70 cc for HAL and 320 +/- 99 cc for OD (p = 0.0001). Mean warm
      ischemia time was 3 +/- 2 minutes for LAP, 2 +/- 2 minutes for HAL and 2 +/- 1
      minutes for OD (p = 0.002). Postoperative hospitalization was 2 +/- 2 days for
      LAP and 3 +/- 2 days for OD (p = 0.01). LAP required 30% less narcotic medicine
      than OD postoperatively (p = 0.04). There were no major complications in LAP
      cases and no complete or partial graft loss was noted. Mean followup was 7
      months. Recipient creatinine was not significantly different for kidneys
      harvested by LAP or OD (p = 0.5). Diuretic mercaptoacetyltriglycine renograms
      were performed in all recipients 1 to 3 days after surgery and mean effective
      renal plasma flow was similar for the 3 groups (p = 0.9). According to telephone
      survey results 85% of LAP, 71% of HAL and 43% of OD patients reported a return to
      normal physical activity within 4 weeks after surgery. Similarly 74% of LAP, 62%
      of HAL and 26% of OD patients were able to return to work within 4 weeks after
      surgery. CONCLUSIONS: Our data show no significant difference in graft function
      between LAP and OD. LAP and HAL were safe and complications were minimal. The
      main difference was that patients treated with LAP and HAL returned to normal
      physical activity and work significantly earlier than those who underwent OD.

PMID- 14665840
TI  - Laparoscopic live donor nephrectomy in the presence of circumaortic or
      retroaortic left renal vein.
AB  - PURPOSE: Laparoscopic live donor nephrectomy is now an accepted alternative to
      open surgery in donors with normal renal vasculature. However, the suitability of
      laparoscopy for donors with anomalous vasculature is less well known. We compared
      the donor and recipient outcome data of 16 patients with circumaortic or
      retroaortic left renal vein to 20 recent patients with normal left renal venous
      anatomy undergoing laparoscopic donor left nephrectomy. MATERIALS AND METHODS: Of
      170 patients undergoing laparoscopic donor nephrectomy at our institution from
      October 1997 to October 2002, 18 (10.6%) had either a circumaortic or retroaortic
      left renal vein (group 1). Demographic and perioperative parameters of these
      donors and their recipients were retrospectively compared to a contemporary
      cohort of 20 recent patients with a normal single left renal vein (group 2).
      RESULTS: All laparoscopic procedures were completed successfully without open
      conversion. Groups 1 and 2 were similar in regard to operative time (199 vs 226
      minutes, p = 0.90), blood loss (125 vs 100 cc, p = 0.45), warm ischemia time (3.4
      vs 3.9 minutes, p = 0.14) and hospital stay (2.9 vs 3.2 days, p = 0.45). Length
      of allograft renal artery and vein was similar between groups. Cold ischemia and
      revascularization times were also comparable between groups. Recipient serum
      creatinine was comparable at 5 days (1.7 vs 1.6 mg/dl), 3 months (1.5 vs 1.4
      mg/dl) and 1 year (1.5 vs 1.5 mg/dl). CONCLUSIONS: Presence of a circumaortic or
      retroaortic renal vein is not a contraindication to laparoscopic live donor left
      nephrectomy. A left kidney with vasculature anatomically adequate for
      transplantation can be achieved with excellent donor and recipient outcomes.

PMID- 14665841
TI  - Laparoscopic donor nephrectomy: the University of Maryland 6-year experience.
AB  - PURPOSE: We determined whether the results of laparoscopic donor nephrectomy
      warranted expansion of the availability of the technique. MATERIALS AND METHODS:
      Donor and recipient charts for 738 consecutive laparoscopic living donor
      nephrectomies have been reviewed. RESULTS: Renal donors were 69% white race and
      57% female. Age range was 18 to 74 years. Neither age nor obesity alone were
      exclusionary criteria. Nephrectomy was left sided in 96%. Donors with body mass
      index greater than 33 had longer operative times. The extraction site changed
      from umbilical to suprapubic during the series. Warm ischemia time was 169
      seconds. Conversion to open nephrectomy occurred in 1.6% of cases and blood
      transfusion was required in 1.2%. Major intraoperative complications occurred in
      6.8% and major postoperative complications occurred in 17.1% of cases.
      Hospitalization lasted 64.4 hours. Postoperative donor creatinine was 1.5 times
      the preoperative level. Recipient serum creatinine averaged 2.0 mg% at 1 week and
      1.6 mg% at 1 year. Delayed graft function occurred in 2.6%. However, 9.1% of
      recipients did not achieve a serum creatinine less than 3.0 mg% within 7 days.
      The endovascular stapler also created 37 extra arteries for implantation.
      CONCLUSIONS: Risks of laparoscopic donor nephrectomy to the donor must not be
      minimized. Rapid conversion to open surgery to control bleeding may be necessary.
      Nonvascular intraoperative injuries require recognition. Slow bowel function
      recovery prolongs hospitalization and may indicate unrecognized pancreatitis or
      small bowel herniation. Surgical technique and complication management have
      improved. Laparoscopic donor nephrectomy is now routine but still requires an
      intense level of attention to prevention of complications.

PMID- 14665842
TI  - Factors related to delayed graft function after laparoscopic live donor
      nephrectomy.
AB  - PURPOSE: Delayed graft function after live donor transplantation affects 5% to
      10% of recipients regardless of procurement technique. This delay in function is
      associated with an increased risk of rejection and decreased graft survival. In
      the present study we critically assess allograft recovery to identify the risk
      factors related to delayed graft function. MATERIALS AND METHODS: We
      retrospectively reviewed donor and recipient medical records from 100 consecutive
      laparoscopic live donor nephrectomies from August 1997 to October 2001. Four
      criteria were used to classify delayed graft function: I) requirement of dialysis
      in postoperative week 1, II) creatinine 2.5 mg/dl or greater at postoperative day
      5, III) time to half peak activity (mercaptoacetyltriglycine renal scan) at
      postoperative day 5 greater than 12.2 minutes (normal range 1 to 12.2) and IV)
      time to peak activity (mercaptoacetyltriglycine renal scan) at day 5 greater than
      6.5 minutes (normal range 2.1 to 6.5). Patients could qualify for multiple
      outcome categories. Patients who did not match any of these criteria were
      classified as having normal renal function (outcome 0). RESULTS: The number of
      patients in the delayed graft function categories were 5 with outcome I, 14 with
      outcome II, 39 with outcome III and 24 with outcome IV. There were 23 patients
      represented in more than 1 category and 59 patients were classified as having
      normal function. Recipient age, donor/recipient gender relationship, unrelated
      highly mismatched donors and cold/total preservation time were identified as risk
      factors related to impaired early renal function recovery. None of the variables
      related to the laparoscopic technique itself represented risk factors for delayed
      graft function. CONCLUSIONS: Female donor kidneys into male recipients and highly
      HLA mismatched donors represent factors that may be controlled by donor selection
      when feasible. All attempts should be made to decrease cold ischemia time and,
      therefore, total preservation time. Prolonged carbon dioxide pneumoperitoneum,
      warm ischemia time, renal artery length or use of right kidney did not adversely
      affect the functional outcome of the allografts procured laparoscopically.

PMID- 14665843
TI  - Ex vivo ureteroscopic treatment of calculi in donor kidneys at renal
      transplantation.
AB  - PURPOSE: We evaluated the safety and efficacy of ex vivo ureteroscopy (ExURS) as
      a means of rendering the donated kidney stone-free at live donor renal
      transplantation. MATERIALS AND METHODS: A total of 10 suitable kidney donors with
      small, unilateral nonobstructive calculi underwent live donor nephrectomy (8 open
      flank, 2 hand assisted transperitoneal). Immediately after cold perfusion, ExURS
      was performed in an iced saline solution. Access to the collecting system was via
      the ureteral stump. Calculi were either removed with endoscopic baskets and/or
      completely fragmented with Holmium laser lithotripsy. RESULTS: Access to the
      renal collecting system was technically successful in all cases. A total of 10
      stones, ranging in largest diameter from 1 to 8 mm (average 5.2) were visualized.
      Of the kidneys 6 had solitary stones, 2 had 2 stones and 1 had no stone. Of 10
      stones 9 were successfully removed and/or fragmented with an average procedure
      time of 6.5 minutes (range 3 to 28). Indwelling ureteral stents were placed at
      transplantation in 5 of 10 kidneys. There were no intra-operative or
      postoperative ureteral complications. At 1 month after transplant serum
      creatinine ranged from 0.9 to 2.7 mg/dl (average 1.5). At a mean followup of 33.2
      months new stones have not formed in any recipients and at mean 36.4-month
      followup no new calculi have formed in the remaining kidney of any donors.
      CONCLUSIONS: ExURS is a technically feasible means of rendering a stone bearing
      kidney stone-free without compromising ureteral integrity or renal allograft
      function.

PMID- 14665844
TI  - Living donor nephrectomy.

PMID- 14665845
TI  - Hand-assisted laparoscopic nephrectomy: prospective evaluation of the learning
      curve.
AB  - PURPOSE: Laparoscopic nephrectomy (LN) has recently become an emerging standard
      for extirpative surgery of the kidney. LN has historically proven to have a steep
      learning curve with longer operative times until a surgeon gains adequate
      laparoscopic experience. Hand-assisted laparoscopic nephrectomy (HALN) is fast
      becoming a commonly used procedure to remove kidneys as it may have a reduced
      learning curve compared to standard LN. To date no prospective studies have
      evaluated the learning curve of HALN with regard to improvements in operative
      times and technical difficulty. We prospectively evaluated the learning curve for
      HALN in a residency training program as it compares to open nephrectomy.
      MATERIALS AND METHODS: HALN was performed in 30 consecutive patients for various
      indications. The senior urology resident functioned as the primary surgeon and
      the same attending surgeon was present throughout all cases. All participating
      residents had to have performed at least 15 open nephrectomies to serve as an
      internal, personal reference. Difficulty scores were obtained at the completion
      of the case from the resident surgeon comparing HALN to open nephrectomy, which
      ranged from 1 to 5. Operative times, estimated blood losses and lengths of stay
      were obtained at the time of surgery and hospitalization. RESULTS: Median
      difficulty score was equivalent to open nephrectomy for the first case but
      decreased significantly by case 4 (p = 0.0006). Median operative times decreased
      significantly from 178 minutes in the first cases to 85 minutes by case 6 (p =
      0.0002). Estimated blood loss and length of hospitalization did not differ
      significantly. CONCLUSIONS: HALN has a relatively short learning curve reflected
      by the rapid decrease in difficulty scores and operative times by case 4. Similar
      results may be expected when training practicing urologists to perform HALN.

PMID- 14665846
TI  - Laparoscopic partial nephrectomy in cold ischemia: renal artery perfusion.
AB  - PURPOSE: Laparoscopic partial nephrectomy represents a feasible option for
      patients with small renal masses. We describe our initial experience with
      laparoscopic partial nephrectomy in cold ischemia achieved by renal artery
      perfusion. MATERIALS AND METHODS: From November 2001 to March 2003 laparoscopic
      partial nephrectomy in cold ischemia was performed in 15 patients with renal cell
      carcinoma. Cold ischemia was achieved by continuous perfusion of Ringers lactate
      at 4C through the renal artery, which was clamped. Tumor excision was performed
      in a bloodless field with biopsy taken from the tumor bed. The collecting system
      was repaired if needed. Renal reconstruction was performed by suturing over
      hemostatic bolsters. RESULTS: All procedures were successfully completed
      laparoscopically by our new technique. Mean operative time was 185 minutes (range
      135 to 220). Mean ischemia time was 40 minutes (range 27 to 101). Estimated mean
      intraoperative blood loss was 160 ml (range 30 to 650). Entry to the collecting
      system in 6 patients was repaired intraoperatively. Additional vascular repair
      was done in 2 patients. There were no significant postoperative complications.
      Postoperative followup in 8 patients showed that the renal parenchyma was not
      damaged by the ischemic period. CONCLUSIONS: Our initial experience of
      incorporating cold ischemia via arterial perfusion into laparoscopic partial
      nephrectomy shows the feasibility and safety of the technique. We believe that
      this approach has the potential to make laparoscopic partial nephrectomy for
      renal cell carcinoma safe and reliable.

PMID- 14665847
TI  - Laparoscopic management of extra-adrenal pheochromocytoma.
AB  - PURPOSE: Laparoscopic management of extra-adrenal pheochromocytoma presents a
      unique surgical challenge due to variable anatomical presentation and potential
      catecholamine surge during operative manipulation. We report our experience with
      laparoscopic removal of extra-adrenal pheochromocytomas. MATERIALS AND METHODS:
      Between 1999 and 2002, 5 patients presented with retroperitoneal extra-adrenal
      pheochromocytomas. Of the patients 2 had a history of von Hippel-Lindau disease,
      and the remaining 3 patients were diagnosed with sporadic extra-adrenal
      pheochromocytoma during hypertension evaluation. Although 4 patients had a
      history of hypertension, only 2 reported symptoms (episodic flushing, headaches,
      blurred vision) associated with excess catecholamine production. All patients had
      markedly increased preoperative urinary and plasma normetanephrine and/or
      norepinephrine levels, and 3 had positive I131 metaiodobenzylguanidine scan. In
      each case tumor was accurately identified on computerized tomography before
      surgery. RESULTS: Laparoscopic resection of extra-adrenal pheochromocytoma was
      successful in 4 patients. Open conversion was required in 1 patient, who also had
      von Hippel-Lindau related bilateral adrenal pheochromocytomas due to significant
      adhesion of the extra-adrenal tumor to the aorta and renal hilum, and a concern
      for possible local invasion. Mean laparoscopic operative time and blood loss were
      273 minutes (range 240 to 350) and 119 cc (range 75 to 200), respectively. Three
      10 mm ports in a standard triangular fashion were used for the left side tumors,
      in which the tumors were found lateral to the aorta. For the right side tumors
      located either in the inter-aortacaval or para-caval region, a fourth port (10
      mm) was inserted for liver retraction as needed. Laparoscopic ultrasound was used
      to localize the tumor and to assess the retroperitoneum for possible metastasis
      (none detected) in 3 cases. None of the patients had a hypertensive crisis
      intraoperatively, and all had unremarkable postoperative recovery with an average
      hospital stay of 3.8 days (range 3 to 4). Plasma and/or urinary norepinephrine
      and normetanephrine levels returned to normal range postoperatively in all cases.
      One patient was noted to have left lower extremity lymphedema and gluteal
      hematoma due to a positional injury related to prolonged pressure from the
      operating table and was treated conservatively. There has been no tumor
      recurrence at a median followup of 14 months (range 9 to 36). CONCLUSIONS: With
      careful surgical planning and appropriate preoperative pharmacological blockade,
      laparoscopic surgery can be safely performed in patients with extra-adrenal
      pheochromocytomas with minimal morbidity. Laparoscopic ultrasound may be helpful
      in precise localization and evaluation of tumor extension.

PMID- 14665848
TI  - Laparoscopic management of ureteropelvic junction obstruction in patients with
      upper urinary tract anomalies.
AB  - PURPOSE: We report our experience with the laparoscopic management of
      ureteropelvic junction obstruction in patients with upper urinary tract
      abnormalities. MATERIALS AND METHODS: Between July 1994 and May 2002, 7 men and 4
      women with upper urinary tract anatomical abnormalities were referred to our
      institution for management of symptomatic ureteropelvic junction obstruction.
      Anomalies included horseshoe kidneys in 5 cases, pelvic kidneys in 3, a pancake
      kidney in 1, a malrotated kidney in 1 and a duplicated collecting system in 1.
      Three patients had associated renal stones that were extracted during
      reconstruction. Mean patient age was 37.4 years (range 25 to 60). One patient had
      undergone a previously unsuccessful endopyelotomy and 2 had a history of
      abdominal surgery. RESULTS: Mean operative time was 195 minutes (range 85 to 403)
      and mean estimated blood loss was 122 cc (range 20 to 300). No patient in this
      series required transfusion. Average length of hospital stay was 3.2 days (range
      2 to 5). Renal function failed to improve after surgery in 1 patient with poor
      renal function and severe hydronephrosis. The remaining 10 patients (91%) had
      durable clinical and/or radiographic success during a followup of 32.6 and 21.3
      months, respectively. There were no major complications. CONCLUSIONS:
      Laparoscopic pyeloplasty is an effective treatment alternative for ureteropelvic
      junction obstruction associated with renal or urinary tract anomalies.

PMID- 14665849
TI  - Assessment of basic human performance resources predicts the performance of
      virtual ureterorenoscopy.
AB  - PURPOSE: Regardless of training, innate ability may influence the acquisition of
      endoscopic skills. Until recently objective methods to assess innate ability have
      not been available. We compared objective measures of human basic performance
      resources (BPRs) using nonlinear causal resource analysis (NCRA) and expert rated
      endoscopic performance of medical students on a virtual reality (VR) simulator.
      MATERIALS AND METHODS: BPRs were measured in 18 medical students (group 1) using
      13 validated tests. BPR results were compared to the results of ureteroscopic
      skills assessment on the VR simulator. An NCRA model was devised to predict
      performance based on BPRs and the limiting performance resource (LPR). The same
      BPRs were measured in a second group of 14 medical students (group 2). Using the
      model created from group 1 performance of VR ureterorenoscopy was predicted based
      on LPR for each student in group 2. Predicted performance was compared to rated
      performance. RESULTS: The average difference in score between 2 expert raters was
      7.2%. The average difference in predicted score based on the NCRA model and rated
      score was only 8.0%. In 9 of the 14 group 2 subjects (63%) the performance
      prediction by NCRA was in excellent agreement (+/-10%) with the expert rating on
      the VR simulation. NCRA over predicted performance in 2 subjects (14%) and under
      predicted performance in 3 (21%). CONCLUSIONS: Objective prediction of
      ureteroscopic performance in the VR environment using LPRs (measures of innate
      ability) for each subject is possible and practical using new measurement and
      modeling methods. The selection of surgical candidates, training and the
      educational curriculum could be impacted.

PMID- 14665850
TI  - Outcome of metabolic evaluation and medical treatment for calcium nephrolithiasis
      in a private urological practice.
AB  - PURPOSE: We determine if medications that have been proven effective for kidney
      stone prevention in prospective controlled trials can reduce kidney stone
      recurrence in a private practice of urology better than life-style advice,
      including hydration. MATERIALS AND METHODS: Between July 1, 1995 and December 31,
      1996, 203 patients with stones received care from 1 private practice. Physicians
      chose to evaluate these patients metabolically based on clinical judgement.
      Thiazide, potassium citrate and allopurinol are recognized in this study as
      active treatments, and drug treatment intervals were calculated. Relapse and
      recurrent stones were counted as those stones manifesting after the initial index
      event. A stone was called a relapse stone if its date was included in the active
      treatment interval. RESULTS: The association between use of active therapy and
      ordering of metabolic evaluation was highly significant. Using survival tables,
      we separately considered all patients and only those who had formed more than 1
      stone. For both populations active treatment reduced stone recurrence
      significantly more than diet advice and hydration. CONCLUSIONS: Medications
      validated in trials and guided by metabolic evaluation lower stone recurrence
      when used in a private practice setting as they do in trials.

PMID- 14665851
TI  - Endoscopic features of impacted ureteral stones.
AB  - PURPOSE: We retrospectively evaluated endoscopic findings in 165 patients with
      impacted ureteral stones to determine the incidence of associated ureteral
      lesions and predisposing factors for such lesions. MATERIALS AND METHODS: From
      July 1993 to March 2003 we performed retrograde endoscopic treatment in 165
      patients with ureteral stones that had been impacted for more than 2 months.
      Average maximum stone diameter was 15.0 mm and the mean duration of impaction was
      17.6 months. Treatment was done with small caliber ureteroscopes and a laser
      lithotriptor. We analyzed the endoscopic findings and determined the outcome by
      reviewing the clinical records and radiographic studies. RESULTS: Endoscopic
      observation revealed inflammatory ureteral polyps associated with calculi in 51
      patients (30.9%). Endoscopic biopsy of 5 polyps was performed. Histological
      examination showed no malignancy and only chronic granulomatous inflammation of
      the ureter. Endoscopic observation also detected ureteral stricture in 28
      patients (17.0%). Patients with polyps and strictures had long-term impaction
      (median 12 and 24 months, respectively), which was significantly longer than in
      patients without ureteral lesions (4 months). CONCLUSIONS: Endoscopic observation
      revealed that long-term impacted stones were frequently associated with ureteral
      polyps and strictures. Although concurrent ureteral lesions can make it more
      difficult to approach the calculus in patients with impacted stones, we found
      that a small caliber flexible endoscope was effective and laser fragmentation
      could be achieved easily.

PMID- 14665852
TI  - Raman spectroscopic analysis identifies testicular microlithiasis as intratubular
      hydroxyapatite.
AB  - PURPOSE: As diagnosed by ultrasonography, testicular microlithiasis is associated
      with various benign and malignant conditions. The molecular constitution of these
      microliths is largely unknown. Raman spectroscopy provides detailed in situ
      information about the molecular composition of tissues and to our knowledge it
      has not been applied to gonadal microliths. We analyzed the molecular composition
      of gonadal microlithiasis and its surrounding region using Raman spectroscopy in
      malignant and benign conditions. MATERIALS AND METHODS: Multiple microliths from
      6 independent samples diagnosed with gonadal microlithiasis by ultrasound and
      histologically confirmed were investigated by Raman spectroscopy. The samples
      included 4 testicular parenchyma samples adjacent to a germ cell tumor (4
      seminomas), a gonadoblastoma of a dysgenetic gonad and testicular biopsy of a
      subfertile male without malignancy. RESULTS: Raman spectroscopic mapping
      demonstrated that testicular microliths were located within the seminiferous
      tubule. Glycogen surrounded all microliths in the samples associated with germ
      cell neoplasm but not in the benign case. The molecular composition of the 26
      microliths in all 6 conditions was pure hydroxyapatite. CONCLUSIONS: Microliths
      in the testis are located in the seminiferous tubules and composed of
      hydroxyapatite. In cases of germ cell neoplasm they co-localize with glycogen
      deposits.

PMID- 14665853
TI  - Cadherin-6: a new prognostic marker for renal cell carcinoma.
AB  - PURPOSE: Cadherin-6, a new cell adhesion molecule of the cadherin family, is
      expressed in normal kidney and renal cell carcinoma. First results demonstrated
      that the expression of cadherin-6 in renal cell carcinoma may have prognostic
      value. We prospectively evaluated the importance of cadherin-6 in renal tumors in
      a large cohort of patients. MATERIALS AND METHODS: A total of 216 patients with
      renal cell carcinoma who underwent tumor nephrectomy were evaluated for cadherin
      6 expression by immunohistochemistry and immunoblotting. The expression pattern
      was correlated with known prognostic factors of renal cell carcinoma. Statistical
      analysis was performed by the Mann-Whitney U and Pearson chi-square tests.
      Multivariate analysis was performed by the proportional hazard Cox model.
      RESULTS: Cadherin-6 expression in renal cell cancer correlated with known
      prognostic factors, such as pT stage (p = 0.03), pN stage (p = 0.001),
      histological growth pattern (p = 0.001), M stage (p = 0.06) and renal venous
      involvement (p = 0.019). There was no correlation with tumor grading (p = 0.74)
      or tumor size (p = 0.84). We developed a relative risk factor for renal cell
      cancer for our patients using the multivariate proportional hazard Cox model,
      which showed a statistically significant correlation with cadherin-6 expression
      (p = 0.028). CONCLUSIONS: Cadherin-6, a new cell adhesion molecule of the
      cadherin family, is specifically expressed in the proximal tubule of normal
      kidneys and in renal cell cancer. In our prospective analysis the pattern of
      cadherin-6 expression correlated with known prognostic factors of renal cell
      cancer on univariate and multivariate analysis. Our data suggest that cadherin-6
      is a new prognostic factor for renal cancer.

PMID- 14665854
TI  - Management of renal angiomyolipomas associated with tuberous sclerosis complex.
AB  - PURPOSE: Intensive management is generally recommended for angiomyolipomas
      associated with tuberous sclerosis complex (TSC), which are known to have a more
      aggressive nature than sporadic tumors. In this study we evaluated the management
      of these tumors. MATERIALS AND METHODS: The records of 6 men and 6 women with TSC
      and a mean age of 28.8 years) with angiomyolipomas treated from 1984 to 2000 were
      retrospectively analyzed. All patients had bilateral multiple tumors (mean size
      6.6 cm). There were 10 lesions classified as small (less than 4 cm), 6 medium (4
      to 10 cm) and 8 large lesions (10 cm or greater). Computerized tomography was
      repeated annually for followup observation and semiannually after embolization.
      RESULTS: Excluding from study 3 tumors treated prophylactically intervention was
      required in 20%, 50% and 100% of small, medium and large tumors, respectively.
      Among 14 tumors followed by observation, 8 grew and 4 required intervention.
      Uncontrollable hemorrhage did not develop in any patient. While some tumors
      showed remarkable growth in decade 3, growth did not exceed 1.5 cm per year.
      Embolization was performed in 11 tumors and tumors shrank in 10. Although 1
      patient experienced renal atrophy, all patients but 1 are alive without renal
      failure with a mean followup of 60 months. CONCLUSIONS: Although asymptomatic
      angiomyolipomas associated with TSC grow gradually, severe hemorrhage is rare and
      most tumors can be managed conservatively with annual computerized tomography.
      Embolization is the first choice of intervention but should be reserved until
      symptoms develop.

PMID- 14665855
TI  - Renal tumors in young adults.
AB  - PURPOSE: The clinical and pathological features of solid or complex cystic renal
      masses in young adults have not been defined. We present our experience with
      patients 17 to 45 years old with such renal masses to define the incidence of
      malignant vs benign lesions, familial tendencies and clinical outcomes. MATERIALS
      AND METHODS: The medical records of all patients 17 to 45 years old who presented
      with a solid or suspicious complex cystic renal mass at 2 tertiary care hospitals
      between 1988 and 2002 were retrospectively reviewed. Pertinent clinical
      information was compiled, including age, gender, mode of presentation, renal
      function, year and type of surgery, pathological analysis and survival data.
      RESULTS: There were 114 evaluable patients who underwent a total of 119
      nephrectomies. Mean patient age was 37.1 years and males comprised 56.1% of the
      population. Twelve patients had familial renal cell carcinoma (RCC), the von
      Hippel-Lindau syndrome. Mode of presentation for patients with sporadic disease
      was symptomatic (55.9%), incidental (35.3%) or unknown (8.8%). Radical
      nephrectomy, partial nephrectomy and nephroureterectomy were performed in 80
      kidneys (67.2%), 37 (31.1%) and 2 (1.7%), respectively. Malignant lesions
      comprised 79.8% of all masses and 95.8% of these were renal cell carcinoma. Of
      the RCCs 75.8% were grade 1 or 2 and 89% were organ confined. Young women were
      much more likely than men to have a benign lesion (36.0% vs 9.5%, p <0.01) and
      the diversity of histologies was impressive (of the 24 total benign masses 9 were
      different tumor types). With an average followup of 38.3 months overall survival
      is 90.2%. Among patients with RCC 84.9% are alive and cancer-free, 11.6% are dead
      from disease and 3.5% are alive with recurrent disease. CONCLUSIONS: We report
      the largest known series of solid or suspicious complex renal masses in young
      adults. As expected, familial tumors are more common in this population. While
      RCC is the most common tumor, a wide variety of potential pathological outcomes
      are possible, particularly in women, who were much more likely to have a benign
      lesion. RCC in this patient population appears to have a favorable prognosis,
      despite symptomatic presentation in the majority of cases.

PMID- 14665856
TI  - Natural history of renal masses followed expectantly.
AB  - PURPOSE: An increasing number of incidental renal masses have been detected with
      increasing use of ultrasonography, computerized tomography and magnetic resonance
      imaging. We investigated the natural history of incidentally detected renal
      masses. MATERIALS AND METHODS: A total of 24 patients were included in this
      retrospective analysis. Average patient age was 68.3 years (range 29 to 83). The
      16 males and 8 females were followed with abdominal imaging for a mean and median
      followup of 31.6 and 24 months, respectively (range 8 to 86). Patients elected to
      be observed because of age, poor medical condition or the presence of a mass in a
      solitary kidney. The majority of patients (22 of 24) were asymptomatic at
      diagnosis. Two patients were followed with bilateral renal masses, and 2 with T3b
      tumors. Of the 20 patients with incidental solitary renal masses, 6 were at the
      upper pole, 9 were mid polar and 5 lower pole. Mean maximum diameter of lesions
      was 3.3 cm (median 2.7, range 0.9 to 10). Growth rate was calculated based on
      diameter and tumor volume. RESULTS: Of the 24 patients only 5 demonstrated tumor
      growth during the surveillance period. No metastasis developed in any patients.
      Mean tumor growth rate observed in the 5 patients was 0.49 cm per year or 7.3 cc
      per year. Of the 24 patients 4 underwent surgery after surveillance because of
      apparent tumor growth or per patient request. Pathology revealed renal cell
      carcinoma in all 4. CONCLUSIONS: Tumor growth of renal masses is often limited.
      Most of our patients did not demonstrate significant growth when followed
      expectantly. Without tumor growth the risk of metastasis seems limited.

PMID- 14665857
TI  - Telomerase pulsed dendritic cells for immunotherapy for renal cell carcinoma.
AB  - PURPOSE: Renal cell carcinoma (RCC) is known for its immunological
      susceptibility. Unfortunately RCC lacks specific tumor antigens for the induction
      of specific immunotherapy. We investigated the role of telomerase as a tumor
      antigen and pulsed dendritic cells (DCs) as antigen presenting cells with an
      immunogenic peptide from telomerase. MATERIAL AND METHODS: DCs and immunological
      effector cells, that is cytokine induced killer (CIK) cells, from patients with
      RCC or healthy donors were generated. CIK cells were co-cultured with telomerase
      peptide pulsed DCs. CIK cells were tested for cytotoxic activity against primary
      cultures. Using the dimer technique we determined the percent of telomerase
      specific T cells. Activation status was identified using interferon-gamma
      secretion assay. RESULTS: After pulsing DCs with telomerase peptide co-cultured
      CIK cells had a significant increase in cytotoxic activity against tumor cells
      compared with CIK cells without co-culture, that is 100% at an effector-to-target
      ratio of 60:1 vs 41.7% (p <0.05). Using a complete autologous model with
      immunological cells derived from patients with metastatic RCC we were able to
      induce cytotoxicity against autologous, telomerase positive primary cell
      cultures. We could detect 2.4% telomerase specific effector cells after co
      culture with peptide pulsed DCs, which secreted interferon-gamma after re
      stimulation. CONCLUSIONS: Telomerase could serve as a specific tumor associated
      antigen for RCC. The presentation of telomerase peptide by DCs to lymphocytes
      allows the generation of antigen specific cytotoxic effector cells.

PMID- 14665858
TI  - The prediction of renal function 6 years after unilateral nephrectomy using
      preoperative risk factors.
AB  - PURPOSE: Since middle-aged and elderly patients seem to have risk factors
      affecting renal function, it is important to predict postoperative renal function
      prior to unilateral nephrectomy (UNx). We evaluated preoperative factors for
      predicting postoperative renal function in middle-aged and elderly patients with
      renal cell carcinoma (RCC) treated with radical nephrectomy (RNx). MATERIALS AND
      METHODS: In 201 patients who underwent RNx preoperative records and postoperative
      serum creatinine (SCR) 6 years after nephrectomy were available. Postoperative
      renal insufficiency was defined as serum creatinine 1.4 mg/dl or greater. The
      relationship of each preoperative and postoperative factor was analyzed. Logistic
      regression analysis was performed to evaluate preoperative factors for predicting
      postoperative SCR 1.4 mg/dl or greater after 6 years. RESULTS: There was a
      significant difference in postoperative SCR between female and male patients, and
      between those with and without hypertension, diabetes and proteinuria (p <0.05).
      Age, hemoglobin, preoperative SCR, blood urea nitrogen, uric acid and K
      significantly correlated with postoperative SCR (p <0.05). The increase in SCR
      during 6 years after UNx was significantly higher in patients with hypertension,
      diabetes and proteinuria than in their respective counterparts (p <0.05).
      Multivariate stepwise logistic regression analysis demonstrated that preoperative
      serum creatinine, hypertension and proteinuria were significant independent
      factors predicting postoperative renal function 6 years after UNx in patients
      with RCC (p <0.05). CONCLUSIONS: Preoperative SCR, hypertension and proteinuria
      are useful factors for predicting postoperative renal function after RNx in
      patients with RCC.

PMID- 14665859
TI  - Different treatment strategies for end stage renal disease in patients with
      transitional cell carcinoma.
AB  - PURPOSE: Transitional cell carcinoma is the most common urinary tract cancer in
      Taiwanese patients on dialysis. It is a unique finding compared within Western
      countries. Due to this geographic difference and a higher recurrence rate a more
      extensive operation and aggressive followup protocols should be refined for these
      patients on dialysis. MATERIALS AND METHODS: We retrospectively reviewed the
      medical records of all patients with transitional cell carcinoma who had end
      stage renal disease and underwent hemodialysis. Records were reviewed for
      hemodialysis duration, initial tumor location, tumor grade, stage, operative
      method, operative complication and final surgical status. Tumor grade and stage
      was determined by the WHO and proposed Jewett systems. Six patient groups were
      classified according to final surgical status for comparative analysis. RESULTS:
      A total of 30 patients were included in this study. Painless gross hematuria and
      urethral bloody discharge were the most common complaints. Tumor in 25 of the 30
      cases was high grade and all were early stage. Of the patients 11 (36.7%) had
      undergone bilateral nephroureterectomy and radical cystectomy in as a 1 or
      multiple step procedure. Six patients (20%) had undergone bilateral
      nephroureterectomy at 1 or 2 sequential operations. Seven of the 13 patients
      (53.8%) in whom low urinary tract transitional cell carcinoma was initially
      treated with transurethral resection unfortunately had recurrent transitional
      cell carcinoma of the upper urinary tract. Ten of the 14 patients (71.4%) with
      upper urinary tract transitional cell carcinoma who underwent nephroureterectomy
      and bladder cuff excision had subsequent transitional cell carcinoma within the
      bladder. CONCLUSIONS: Patients with transitional cell carcinoma on dialysis had a
      higher recurrence rate in the upper urinary tract than patients not on dialysis.
      Most cases were at an early stage but with high grade tumor behavior. In 11
      patients (36.7%) total exenteration of the urinary tract except the urethra was
      eventually done. The final bilateral nephroureterectomy rate was 56.7%. Since the
      rate of total exenteration and bilateral nephrectomy was abnormally high at such
      a short followup, 1-step bilateral nephroureterectomy and radical cystectomy are
      a recommended treatment for patients with transitional cell carcinoma on
      dialysis.

PMID- 14665860
TI  - Complications of radical and partial nephrectomy in a large contemporary cohort.
AB  - PURPOSE: Standardized criteria for reporting the early complications of
      urological procedures are lacking. We reviewed the early complications of radical
      nephrectomy (RN) and partial nephrectomy (PN) in a large contemporary cohort
      using a standardized complication grading scale. MATERIALS AND METHODS: Between
      1995 and 2002, 1,049 patients underwent RN (66%) or PN (34%) for renal cortical
      neoplasm. Records were reviewed for perioperative complications. Complications
      were graded using a 5-tiered scale based on the severity of impact or intensity
      of therapy required. RESULTS: A total of 235 complications occurred in 180
      patients (17%). Overall 55% and 31% of complications were grade I and grade II,
      respectively. There were 3 perioperative deaths (0.2%). PN was not associated
      with more complications compared to RN when accounting for other variables. PN
      cases had more procedure related complications compared to RN (9% versus 3%,
      respectively, p = 0.0001) due to complications of urinary leak and the
      reintervention rate was subsequently higher (2.5% versus 0.6%, p = 0.02). All but
      1 of the reinterventions for PN involved either endoscopy or radiology. By
      multivariate analysis operative time (p <0.0001) and solitary kidney (p = 0.06)
      were associated with procedure related complications of PN. CONCLUSIONS: RN and
      PN are associated with low rates of serious morbidity and mortality. Compared to
      RN, PN is associated with higher rates of procedure related complications, the
      majority of which are minor. Overall, however, PN is not associated with more
      complications than RN.

PMID- 14665861
TI  - Improved detection of urothelial carcinoma in situ with hexaminolevulinate
      fluorescence cystoscopy.
AB  - PURPOSE: In this European multicenter study we compared hexaminolevulinate (HAL)
      fluorescence cystoscopy and standard white light cystoscopy for the detection of
      carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer.
      MATERIALS AND METHODS: This study was a prospective controlled, within-patient
      comparison of standard and HAL fluorescence cystoscopy. Eligible patients
      received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was
      performed using a D light system, which provided white and blue light at 375 to
      440 nm. The bladder wall was inspected and mapped, first under white light,
      followed by blue light. All tumors and suspicious areas identified under white
      light and by red fluorescence were resected or biopsied. Histological findings
      were assessed by an independent central pathologist blinded to the identity of
      the biopsies. RESULTS: Of 211 evaluable patients 83 (39%) had CIS, of whom 18
      (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard
      and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%)
      was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more
      patients with CIS than standard cystoscopy. The side effects of HAL instillation
      were negligible and no unexpected events were reported. CONCLUSIONS: HAL
      fluorescence cystoscopy improves the detection of bladder CIS significantly,
      which has consequences for clinical management and may improve the patient
      prognosis. The procedure is easily implemented as an adjunct to standard
      cystoscopy and it adds no significant risk of complications.

PMID- 14665862
TI  - Extended radical lymphadenectomy in patients with urothelial bladder cancer:
      results of a prospective multicenter study.
AB  - PURPOSE: Previous studies demonstrate a positive correlation between
      postoperative survival and the extent of pelvic lymphadenectomies in patients
      with bladder cancer. However, the distribution of nodal metastases has not been
      examined in sufficient detail. Therefore, we conducted a comprehensive
      prospective analysis of lymph node metastases to obtain precise knowledge about
      the pattern of lymphatic tumor spread. MATERIALS AND METHODS: Between 1999 and
      2002 we performed 290 radical cystectomies and extended lymphadenectomies.
      Cranial border of the lymphadenectomy was the level of the inferior mesenteric
      artery, lateral border was the genitofemoral nerve and caudal border was the
      pelvic floor. We made every effort to excise and examine microscopically all
      lymph nodes from 12 well-defined anatomical locations. RESULTS: Mean total number
      and standard deviation of lymph nodes removed was 43.1 +/- 16.1. Nodal metastases
      were present in 27.9% of patients. The percentage of metastases at different
      sites ranged from 14.1% (right obturator nodes) to 2.9% (right paracaval nodes
      above the aortic bifurcation). By studying cases of unilateral primary tumors or
      with only 1 metastasis we observed a preferred pattern of metastatic spread.
      However, there were many exceptions to the rule and we did not identify a well
      defined sentinel lymph node. CONCLUSIONS: We strongly recommend extended radical
      lymphadenectomy to all patients undergoing radical cystectomy for bladder cancer
      to remove all metastatic tumor deposits completely. The operation can be
      conducted in routine clinical practice and our data may serve as a guideline for
      future standardization and quality control of the procedure.

PMID- 14665863
TI  - Is there a role for surgery in the management of metastatic urothelial cancer?
      The M. D. Anderson experience.
AB  - PURPOSE: Although rarely curative, chemotherapy remains the mainstay of treatment
      for metastatic urothelial cancer. The role of surgery for metastatic disease is
      not well established for urothelial cancer, but is sometimes undertaken in the
      face of persistent or recurrent disease that can be surgically resected.
      MATERIALS AND METHODS: We identified 31 patients with metastatic urothelial
      cancer undergoing metastasectomy with the intent of rendering them free of
      disease. All gross disease was completely resected in 30 patients (97%). The most
      frequently resected location was lung in 24 cases (77%), followed by distant
      lymph nodes in 4 (13%), brain in 2 (7%) and a subcutaneous metastasis in 1 (3%).
      RESULTS: Median survival from diagnosis of metastases and from time of
      metastasectomy was 31 and 23 months, respectively. The 5-year survival from
      metastasectomy was 33%. Median time to progression following metastasectomy was 7
      months. Five patients were alive and free of disease for more than 3 years after
      metastasectomy. CONCLUSIONS: The results in this highly selected cohort, with 33%
      alive at 5 years after metastasectomy, suggest that resection of metastatic
      disease is feasible and may contribute to long-term disease control especially
      when integrated with chemotherapy. Further prospective studies should be
      undertaken to better characterize the selection criteria and benefit from this
      intervention.

PMID- 14665864
TI  - Initial tumor stage and grade as a predictive factor for recurrence in patients
      with stage T1 grade 3 bladder cancer.
AB  - PURPOSE: We evaluated whether the risk of progression and the recurrence rate
      were different in patients with primary and nonprimary stage T1 grade 3
      transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between 1983
      and 1997, 75 patients were treated for stage T1 grade 3 transitional cell
      carcinoma of the bladder. Of these patients 68 (primary and nonprimary tumor in
      58 and 14, respectively) without carcinoma in situ who had not undergone complete
      cystectomy immediately after diagnosis were included in the study. No maintenance
      regimen was used. Median followup was 100 months (range 9 to 217). RESULTS: The
      incidence of multiple tumors in patients with nonprimary tumors was significantly
      higher than in patients with primary disease (p = 0.035). However, the recurrence
      free survival rate in patients with primary T1 GIII bladder tumor was
      significantly lower than that of patients with nonprimary T1 GIII bladder tumor
      (p = 0.0016). Multivariate analysis using Cox's proportional hazard regression
      model revealed that only initial tumor status had statistically significant
      effects on tumor recurrence (p = 0.007) and no other factors had a significant
      influence on recurrence-free survival. Progression-free and cancer specific
      survival rates were also significantly different between the 2 groups (p = 0.036
      and 0.0307, respectively). CONCLUSIONS: Our study indicates that patients with
      primary stage T1 grade 3 bladder cancers have higher recurrence and progression
      potential than those with nonprimary disease despite the higher incidence of
      multiple tumors in patients with nonprimary tumors.

PMID- 14665865
TI  - A randomized controlled trial of short-term versus long-term prophylactic
      intravesical instillation chemotherapy for recurrence after transurethral
      resection of Ta/T1 transitional cell carcinoma of the bladder.
AB  - PURPOSE: In a prospective randomized controlled study, we investigated the
      optimal schedule for intravesical instillation of epirubicin for maximizing its
      effect on prophylaxis and disease progression after transurethral resection of
      newly diagnosed Ta/T1 bladder cancer. MATERIALS AND METHODS: The patients were
      instilled with epirubicin (30 mg/30 ml in normal saline) within 24 hours after
      transurethral resection and then randomized into 2 groups after a definite
      histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients
      received 19 intravesical instillations of epirubicin in the year after
      transurethral resection (group 1). The second group of 73 patients received 9
      intravesical instillations of epirubicin during the 3 months after transurethral
      resection (group 2). Nonrecurrence rates and toxicity were compared. RESULTS: In
      the followup period, 10 group 1 patients (13.0%) and 23 group 2 patients (31.5%)
      had recurrent disease. The 3-year nonrecurrence rate was 85.2% in group 1,
      whereas it was 63.9% in group 2. The nonrecurrence rate of group 1 was
      significantly higher than that of group 2 throughout the observation period (p =
      0.005). The incidence and severity of toxicity were not significantly different
      between the 2 groups. CONCLUSIONS: Our study indicates that long-term
      instillation of epirubicin is more effective than short-term instillation in
      preventing recurrence after transurethral resection of Ta/T1 bladder cancer.

PMID- 14665866
TI  - Bilateral testicular microlithiasis predicts the presence of the precursor of
      testicular germ cell tumors in subfertile men.
AB  - PURPOSE: A high prevalence of testicular microlithiasis has been described in
      adolescent and adult clinical cases of invasive testicular germ cell tumor
      (TGCT), that is seminomas and nonseminomas. However, to our knowledge it remains
      to be established whether testicular microlithiasis also indicates the presence
      of the pre-invasive lesion of this cancer, known as carcinoma in situ (CIS). We
      determined the predictive value of unilateral and bilateral testicular
      microlithiasis for CIS in subfertile men, a known risk population for TGCTs
      (approximately 1%). MATERIALS AND METHODS: In a retrospective cross-sectional
      study the association between testicular microlithiasis and CIS was studied in a
      group of 263 men referred for subfertility. Testicular microlithiasis and CIS
      were diagnosed in all men by scrotal ultrasound and in testicular histology
      specimens as part of the routine evaluation of all patients. RESULTS: Of the 263
      subfertile men 53 (20%) had testicular microlithiasis. No CIS or TGCT was
      identified in the 23 men with unilateral testicular microlithiasis. In contrast,
      6 of the 30 men (20%) with bilateral testicular microlithiasis were diagnosed
      with CIS. Therefore, the prevalence of CIS in subfertile men with bilateral
      testicular microlithiasis is significantly higher than in patients without
      testicular microlithiasis (1 of 210, 0.5%) and with unilateral testicular
      microlithiasis (0 of 23, 0%) (p <0.0001). CONCLUSIONS: Bilateral testicular
      microlithiasis is indicative for CIS in subfertile men. Since these men are at
      particular risk for invasive TGCT, an assessment of testicular microlithiasis is
      a valuable tool for the early diagnosis of this disease.

PMID- 14665867
TI  - Experience with testis sparing surgery for testicular teratoma.
AB  - PURPOSE: Testicular teratoma is a rare neoplasm affecting the pediatric
      population and has classically been reported to be the second most common testis
      tumor in children behind yolk sac tumors. Testicular teratomas are benign and
      partial orchiectomy may be considered. We describe our single institution
      experience with testicular teratoma and definitive treatment with testis
      preserving surgery. MATERIALS AND METHODS: We reviewed the pathology records at
      our institution for all testicular and paratesticular tumors diagnosed between
      1976 and November 2002 in males younger than 18 years. We specifically examined
      the prepubertal incidence of teratoma, including epidermoid cysts, and our
      experience with testis preserving surgery. Preoperative and postoperative
      ultrasonography images were used to calculate the atrophy index following
      surgery. Patients were contacted for long-term followup. RESULTS: Of 77 primary
      testicular and paratesticular tumors 38 were diagnosed in prepubertal boys (age
      younger than 13 years) including 11 mature teratomas and 5 epidermoid cysts. Mean
      patient age at treatment was 34.4 months (range 4 months to 10 years). All boys
      presented with a painless scrotal mass, cystic foci within an intratesticular
      mass on ultrasound and a normal alpha-fetoprotein level. Of the 16 boys with
      benign teratomas 13 (81%) were treated with a testis sparing procedure. At a mean
      7-year followup no patient has presented with recurrent tumor in the ipsilateral
      or contralateral testicle. Postoperative physical examination and scrotal
      ultrasound were obtained in 9 patients at a median followup of 10.2 months, and
      there was no evidence of testicular atrophy or persistent discomfort.
      CONCLUSIONS: Unlike previously published series based on tumor registries, benign
      teratoma was the most common pediatric testicular tumor treated at our
      institution. Our single institution experience with testis preservation and long
      term followup confirms the role and safety of this technique. Testis sparing
      surgery remains our technique of choice for testicular teratoma.

PMID- 14665868
TI  - Incidence of contralateral germ cell testicular tumors in South Europe: report of
      the experience at 2 Spanish university hospitals and review of the literature.
AB  - PURPOSE: The crude and cumulative incidence of contralateral germ cell testicular
      tumors (GCTTs) is between 1% to 5% and 3% to 6% at 10 to 15 years in previously
      reported studies. To evaluate the real incidence of a second GCTT in a southern
      European population the medical records of 623 patients with GCTT successfully
      treated between 1976 and 1993 at 2 university hospitals were reviewed. MATERIALS
      AND METHODS: All patients had been treated with standard treatment strategies
      according to disease stage and diagnosis year. Contralateral biopsy at GCTT
      diagnosis was not performed in any patient. Only those with a survival of 1 year
      or greater were included. In addition to the imaging and biochemical (tumor
      markers) procedures used to diagnose disease relapse, physical examination of the
      contralateral testis and/or testicular ultrasound was done yearly. RESULTS: At a
      median followup of 8.6 years (range 2 to 19.7) 6 patients (1%) had a
      contralateral GCTT, which was synchronous in 1 and metachronous in 5. The
      cumulative risk of a contralateral GCTT was 1.2% (95% CI 0.1% to 2.3%) at 15
      years and it did not depend on the treatment for the first GCTT. CONCLUSIONS: The
      incidence of contralateral GCTT in our series was lower than expected compared
      with other published series. This finding mirrors the lower incidence of GCTT in
      the general population in our country than in other areas with a higher incidence
      of contralateral GCTT. Therefore, contralateral testicular biopsy at initial
      diagnosis is not mandatory in our experience.

PMID- 14665869
TI  - Tumor marker levels in post-chemotherapy cystic masses: clinical implications for
      patients with germ cell tumors.
AB  - PURPOSE: Increased tumor markers after induction chemotherapy for patients with
      germ cell tumor usually represent systemic disease and consequently second line
      chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND)
      is reserved for patients with marker normalization. We report the concentration
      of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of
      post-chemotherapy cystic masses to evaluate this as a potential source for serum
      marker elevation. MATERIALS AND METHODS: From March 2002 to December 2002, 11
      consecutive patients with post-chemotherapy cystic masses underwent RPLND.
      Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post
      chemotherapy RPLNDs were performed in patients with increased serum tumor
      markers, including the 3 patients in our study. Patients with increasing tumor
      markers and/or multifocal disease with noncystic residual masses after induction
      chemotherapy underwent salvage chemotherapy despite teratomatous elements in the
      primary tumor. RESULTS: All 11 patients had teratoma in the orchiectomy specimen
      and retroperitoneum, including one with malignant transformation. Cystic fluid
      markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and
      9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before
      surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both
      serum markers normalized postoperatively. One patient with increased pre-RPLND
      serum HCG (11.6) had a cyst level of 233. HCG continued to increase
      postoperatively and the patient died of disease. The remaining 10 patients remain
      disease free. CONCLUSION: Fluid from cystic teratoma contains variably elevated
      levels of HCG and AFP in all patients and appears to be independent of serum
      marker level or pathology. It is possible that a "slow leak" of fluid from cystic
      teratoma may explain elevated serum markers in selected patients with teratoma
      and thus may potentially avoid second line chemotherapy.

PMID- 14665870
TI  - A simple model for predicting nodal metastasis in patients with clinical stage I
      nonseminomatous germ cell testicular tumors undergoing retroperitoneal lymph node
      dissection only.
AB  - PURPOSE: In patients with clinical stage I nonseminomatous germ cell testicular
      tumor the identification of risk categories for nodal metastases and/or distant
      metastases could permit selective management. We built 2 models for
      distinguishing these risk categories. MATERIALS AND METHODS: Data on 322
      consecutive patients with clinical stage I nonseminomatous germ cell testicular
      tumor patients treated with retroperitoneal lymphadenectomy (RPLND) alone between
      1985 and 1995 were analyzed. The interval between orchiectomy and RPLND, vascular
      invasion (VI), pT stage, percent embryonal carcinoma (ECa) and teratoma in the
      primary tumor were considered clinically relevant for their association with
      nodal or distant metastases. Two logistic models were constructed. Model 1 was
      meant to discriminate 2 patient categories, namely those with and without nodal
      metastases at RPLND. Model 2 was meant to discriminate 3 patient categories,
      namely those without any metastases, with nodal metastases only and with distant
      metastases independent of retroperitoneal metastases. The models were based on
      these above variables, which were inserted as categorical and then processed
      through a backward selection procedure. RESULTS: At RPLND nodal metastases were
      found in 60 patients (18.6%). During followup distant metastases were observed in
      43 patients (13.4%) and retroperitoneal recurrences were noted in 6 (1.9%). Of
      all recurrences 93.8% were within 2 years since RPLND. RPLND had a high curative
      rate since 73% of all pN+ cases were cured by surgery alone. The final logistic
      model 1, including percent ECa and VI, was reassessed in 202 patients with
      available data. Absent VI and ECa 90% or greater identified a category of 110
      patients at low risk for nodal metastasis (14%), while VI and/or ECa greater than
      90% identified a category of 92 at higher risk (35%). The identified categories
      were also related to distant metastases, which occurred in 9.3% of low risk and
      in 23.1% of high risk cases. Model 2 was not clinically suitable because it did
      not allow us to distinguish patients at risk for nodal metastases only from those
      at risk for distant metastases. CONCLUSIONS: Simplicity is the main advantage of
      model 1 since only 2 well-known prognostic parameters are involved. Although the
      model must be validated in an independent case series, the identification of a
      low risk category with few expected nodal metastases could permit us to replace
      traditional RPLND with a less invasive staging procedure.

PMID- 14665871
TI  - Comparison of accuracy between the Partin tables of 1997 and 2001 to predict
      final pathological stage in clinically localized prostate cancer.
AB  - PURPOSE: We validated externally the predictive accuracy of the 2001 Partin
      tables and compared the 1997 and 2001 versions. MATERIALS AND METHODS: We used
      ROC derived AUC to test the predictive accuracy of organ confinement (OC),
      extraprostatic extension (ECE), seminal vesicle invasion (SVI) and lymph node
      involvement (LNI) of 1997 and 2001 Partin tables derived probabilities. These
      probabilities were defined by the pretreatment clinical stage, serum prostate
      specific antigen and biopsy Gleason grade of 2,139 patients treated with radical
      prostatectomy for clinically localized prostate cancer. RESULTS: OC, ECE, SVI and
      LNI were noted in 63.5%, 23.1%, 10.5% and 2.9% of cases, respectively. AUC of the
      2001 tables was 0.787, 0.766, 0.775 and 0.790, for OC, ECE, SVI and LNI,
      respectively. These values were virtually the same as the respective 1997 Partin
      table AUC values, namely 0.784, 0.728, 0.791 and 0.799. CONCLUSIONS: This
      external validation of the 2001 Partin tables confirms good predictive accuracy
      of the updated tables. However, predictive accuracy in this external validation
      data set of 2,139 European men is virtually the same as that of the original 1997
      tables. Therefore, a transition from the 1997 tables to the updated 2001 version
      does not appear warranted unless superior accuracy is demonstrated in other
      external cohorts.

PMID- 14665872
TI  - Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a
      comparative study with prostate specific antigen parameters.
AB  - PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome
      17p13.1 are currently the most common genetic abnormalities associated with many
      different types of human malignancies. Recently serum p53 antibodies (p53-Abs)
      have been detected in the serum of patients with various cancers. To evaluate the
      clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific
      antigen (PSA) parameters in patients with benign prostatic disease (BPD) and
      prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50
      patients with BPD and 103 with histologically diagnosed prostate cancer,
      including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer
      was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II
      (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free
      and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA
      kit. The clinical values of p53-Abs were compared with total PSA, PSA density
      (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA
      ratio using ROC curves. RESULTS: All patients with prostate cancer had
      significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD.
      While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with
      stage progression, serum p53-Abs were not related to clinical stage. The Gleason
      sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups.
      Patients with T1c cancer had significantly higher p53-Abs than those with BPD.
      According to ROC curve analysis to distinguish prostate cancer from BPD the p53
      Abs titer had the greatest AUC in the overall patient population and in patients
      without digital rectal examination findings. CONCLUSIONS: These results suggest
      that p53-Abs might be helpful in the clinical decision to perform prostate
      biopsy. In the current study the serum p53-Abs titer had the most useful validity
      in discriminating between prostate cancer and BPD in the overall patient
      population and in patients with normal digital rectal examination.

PMID- 14665873
TI  - Hepsin is highly over expressed in and a new candidate for a prognostic indicator
      in prostate cancer.
AB  - PURPOSE: Other cDNA microarray studies have shown that hepsin is one of the
      highly over expressed genes in prostate cancer tissue compared with nonmalignant
      and benign prostatic hyperplasia tissue. We quantitatively analyzed hepsin gene
      expression with real-time polymerase chain reaction and calculated its
      relationships with clinicopathological parameters in a large cohort of samples.
      MATERIALS AND METHODS: Matched prostate tissue samples from the cancerous and
      noncancerous parts of the same prostates were obtained from 90 patients with
      prostate cancer who underwent radical prostatectomy. Quantitative reverse
      transcriptase-polymerase chain reaction was performed using LightCycler Fast
      Start DNA Master SYBR Green I on a LightCycler (Roche Diagnostics GmbH, Mannheim,
      Germany) system. The ratio of hepsin-to-beta-actin (a housekeeping gene) was used
      to normalize data. RESULTS: Hepsin over expression in cancerous compared with
      noncancerous tissue was found in 81 of the 90 patient samples (90%, p <0.001). In
      48 patients (53%) hepsin over expression was more than 10-fold in cancerous
      tissue. The ratio of cancerous-to-noncancerous hepsin expression was
      significantly higher in the 39 patients with grade 3 tumors compared with the 51
      with grade 2 tumors (median 15.5 vs 9.6, p = 0.031). For the prognosis a cutoff
      at the 75th percentile provided a significant difference between patients at
      lower risk (pT2, G2 and Gleason score less than 7) and higher risk (pT3/4, G3 and
      Gleason score 7 or greater) for relapse. CONCLUSIONS: This report of the
      quantitative analysis of hepsin expression, which is the first to our knowledge,
      shows strong and significant over expression in prostate cancer tissue. Hepsin
      expression may be a new prognostic marker that could be used for assessing
      prostate cancer aggressiveness.

PMID- 14665874
TI  - Elevated expression of inhibin alpha in prostate cancer.
AB  - PURPOSE: Less than 50% of men who undergo radical prostatectomy for prostate
      cancer are cured of disease. We evaluate tumor expression of inhibin alpha, a
      putative tumor suppressor, and the related protein, follistatin, to determine
      whether expression correlated with failure to be cured by surgery. MATERIALS AND
      METHODS: Tissues were selected from an archival collection of 379 prostatectomy
      specimens from men with followup of at least 5 years after surgery. Since
      previous studies showed that such men with only Gleason grade 3 cancer had a
      greater than 95% chance of no biochemical recurrence (increase in serum prostate
      specific antigen), our investigation was confined to 174 men with 2% or greater
      grade 4/5 cancer. These men had an intermediate rate of failure, providing an
      opportunity to analyze the potential contribution of inhibin alpha or follistatin
      to progression. Intensity of immunohistochemical labeling for inhibin alpha and
      follistatin in each cancer was compared with that in normal glands within the
      same tissue section. RESULTS: The majority of cases showed more intense
      expression of inhibin alpha in cancer than in normal glands. Those individuals
      whose cancers had the most elevated expression of inhibin alpha had a higher risk
      of recurrence, although this association was not statistically significant.
      Follistatin was expressed equivalently in normal and cancer cells in the majority
      of cases and did not correlate with recurrence. CONCLUSIONS: Our finding that
      inhibin alpha is frequently overexpressed in high grade prostate cancer suggests
      that the role of inhibin alpha as a tumor suppressor needs to be reevaluated.
      Furthermore, assessment of inhibin alpha as a serum marker of prostate cancer, as
      used to diagnose ovarian cancer, may be warranted.

PMID- 14665875
TI  - The incidence of prostate cancer in men with prostate specific antigen greater
      than 4.0 ng/ml: a randomized study of 6 versus 12 core transperineal prostate
      biopsy.
AB  - PURPOSE: The prostate cancer detection rate in patients with elevated prostate
      specific antigen (PSA) increases with extended needle biopsy protocols.
      Transperineal biopsy under transrectal ultrasound guidance is rarely reported,
      although notable cancer diagnoses are obtained with this technique. We describe
      the results of 6 and 12 core transperineal biopsy. MATERIALS AND METHODS: A total
      of 214 patients with PSA greater than 4.0 ng/ml were prospectively randomized to
      undergo 6 or 12 core transperineal biopsy. Each group of 107 patients was
      comparable in terms of clinical characteristics. The procedure was performed on
      an outpatient basis using local anesthesia. Specimens were obtained with a fan
      technique with 2 puncture sites slightly above the rectum (1 per lobe) under
      transrectal ultrasound guidance. Cores were taken from all peripheral areas,
      including the far lateral aspect of the prostate. RESULTS: The overall cancer
      detection rate was 38% and 51% for 6 and 12 core biopsy, respectively. In
      patients with PSA between 4.1 and 10 ng/ml the cancer detection rate was 30% and
      49% for 6 and 12 core biopsy, respectively. CONCLUSIONS: The 12 core
      transperineal prostate biopsy is superior to 6 core biopsy. The technique
      provides optimal prostate cancer diagnosis. About half of the patients with PSA
      greater than 4.0 ng/ml and a slightly lower percent with PSA between 4.1 and 10
      ng/ml have prostate cancer.

PMID- 14665876
TI  - Assessment of the enhancement in predictive accuracy provided by systematic
      biopsy in predicting outcome for clinically localized prostate cancer.
AB  - PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on
      prostate specific antigen (PSA), tumor stage and grade. We investigated whether
      the addition of prostate biopsy features may enhance the accuracy of a nomogram
      predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS:
      Clinical data from 1,152 patients who underwent RP were used and included PSA,
      clinical stage, biopsy Gleason grade and systematic biopsy information that
      quantified the amount of cancer and high grade cancer. Predictive accuracy for
      freedom from recurrence after RP was assessed with and without tumor
      quantification in the biopsy by the area under the receiver operating
      characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer,
      and percentage and number of cores with high grade cancer were predictors of
      outcome when added to models that included PSA, Gleason grade and clinical stage
      (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was
      minimally enhanced with the addition of percentage or number of positive cores
      (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high
      grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of
      0.811 was achieved after supplementing the traditional 3-variable nomogram with
      various combinations of additional pathological predictors. CONCLUSIONS: The
      information provided by systematic biopsies substantially improves the ability to
      predict outcome following RP. However, some incremental predictive accuracy was
      achieved by adding systematic biopsy features.

PMID- 14665877
TI  - Six additional systematic lateral cores enhance sextant biopsy prediction of
      pathological features at radical prostatectomy.
AB  - PURPOSE: We evaluated the contribution of 6 additional systematically obtained,
      laterally directed biopsy cores to traditional sextant biopsy for the prediction
      of final pathological findings in the radical prostatectomy specimen. MATERIALS
      AND METHODS: We studied 178 consecutive patients with no history of prostate
      biopsy in whom prostate cancer was diagnosed during an initial systematic 12 core
      biopsy and who subsequently underwent radical prostatectomy. Of the systematic 12
      cores we compared the subset of the 6 traditional sextant cores (S6C), the set of
      6 laterally directed cores (L6C) and the complete 12 core set, which included the
      6 traditional sextant and the 6 laterally directed cores. Biopsy Gleason score,
      number of positive cores, total cancer length and percent of tumor in the biopsy
      sets were examined for their ability to predict extracapsular extension, total
      tumor volume and pathological Gleason score. RESULTS: On univariable analyses the
      biopsy parameters of the complete 12 core set correlated more strongly with
      extracapsular extension and total tumor volume than the biopsy parameters of S6C
      or L6C. On multivariable analyses S6C and L6C were independent predictors of
      pathological features at prostatectomy. CONCLUSIONS: The addition of 6
      systematically obtained, laterally directed cores to traditional sextant biopsy
      improved the ability to predict pathological features at prostatectomy by a
      statistically and prognostically significant margin. Preoperative nomograms that
      use data from a full complement of 12 systematic cores, specifying sextant and
      laterally directed biopsy cores, should demonstrate improved performance in
      predicting prostatectomy pathology.

PMID- 14665878
TI  - 10-year outcome for men with localized prostate cancer treated with external
      radiation therapy: results of a cohort study.
AB  - PURPOSE: We determine the efficacy of conventional dose, external beam radiation
      for localized prostate cancer using cohort analysis with maximized followup.
      MATERIALS AND METHODS: A total of 205 men with T1-2 prostate cancer were treated
      with conventional external beam radiation to a median and modal dose of 68.4 Gy
      during a 16-month period from 1991 to 1993. Followup was maximized in these
      patients, and median followup for those alive with or without disease was 114
      months. RESULTS: Median patient age at treatment was 72 years, and overall
      survival at 5 and 10 years was 78% and 53%, respectively. The actuarial risk of
      local failure was 18% at 10 years as was the risk of metastatic disease. The
      actuarial risk of being free of biochemical failure at 10 years (American Society
      for Therapeutic Radiology and Oncology definition) was 49%. That risk was 42% if
      the definition was used without backdating failure to a time between last low
      value and first increase. When a crude analysis of 10-year outcome was performed
      127 of the 205 treated patients (62%) were still alive, including 59% with no
      evidence of biochemical failure and a median prostate specific antigen of 1.0
      ng/ml. Of the 78 men (38% of total) who died during the 10 years 32 died either
      of or with recurrent cancer. CONCLUSIONS: Mature followup minimizes many of the
      biases seen in previously published radiation series. This study provides a
      yardstick against which newer radiation modalities may be measured.

PMID- 14665879
TI  - Patterns of secondary cancer treatment for biochemical failure following radical
      prostatectomy: data from CaPSURE.
AB  - PURPOSE: Biochemical failure after definitive treatment for localized prostate
      cancer may occur in a substantial number of patients. The pattern and type of
      treatment offered to such patients have been poorly documented. We determined
      second treatment patterns in patients with biochemical failure following radical
      prostatectomy (RP). MATERIALS AND METHODS: A total of 303 patients treated with
      RP who had biochemical failure were identified from CaPSURE (Cancer of the
      Prostate Strategic Urologic Research Endeavor, Tap Pharmaceutical Products, Inc.,
      Lake Forest, Illinois), a national longitudinal registry of men with prostate
      cancer. Failure was defined as 2 or more prostate specific antigen (PSA) values
      0.2 or greater following RP. The timing and type of secondary cancer treatment
      were determined. Cox proportional hazards regression analysis was conducted to
      determine significant predictors of time to secondary treatment, and logistic
      regression was used to determine predictors of the type of secondary treatment
      (androgen deprivation versus radiation). RESULTS: Of the 303 patients with
      biochemical failure 102 (33.7%) received second treatment a mean of 12 months
      after failure was documented. Second treatments were divided between androgen
      deprivation (57%) and radiation (43%). On multivariate analysis predictors of
      second treatment were clinical stage, biopsy Gleason score and PSA at failure.
      Patients with higher PSA at diagnosis and seminal vesicle invasion were more
      likely to receive androgen deprivation than radiation as second treatment.
      CONCLUSIONS: Second treatment timing and type after biochemical failure for
      patients initially treated with RP were documented. Clinical characteristics,
      such as PSA, Gleason score and clinical stage, can be used to determine which
      patients are at highest risk for second treatment after RP and can help guide
      subsequent treatment decisions.

PMID- 14665880
TI  - 1-stage urethral reconstruction using colonic mucosa graft for the treatment of a
      long complex urethral stricture.
AB  - PURPOSE: We investigated the possibility of urethroplasty with a free graft of
      colonic mucosa for long, complex urethral strictures. We report our initial
      experience with colonic mucosa graft urethroplasty for such urethral strictures
      in 16 patients. MATERIALS AND METHODS: Between September 2000 and December 2002,
      16 patients with a long, complex urethral stricture were treated with colonic
      mucosal graft urethroplasty. Patients had undergone an average of 2.5 previous
      unsuccessful repairs. Urethral reconstruction was done with a 10 to 17 cm (median
      13) graft of colonic mucosa RESULTS: Patients were followed 6 to 33 months
      postoperatively. Meatal stenosis that developed in 1 patient 3 months
      postoperatively needed reoperation. The patient was voiding well with a urinary
      peak flow of 28.7 ml per second during 9-month followup after reoperation.
      Hyperplasia of the verumontanum was observed during urethroscopy and
      transurethral colliculectomy was performed in 1 patient more than 14 months
      postoperatively. Uroflowmetry showed a urinary peak flow of 46.5 ml per second
      postoperatively. The other patients were voiding well with a urinary peak flow of
      greater than 15 ml per second. Urethrogram revealed a patent urethra with an
      adequate lumen and no significant graft sacculation. CONCLUSIONS: This initial
      experience in 16 patients indicates that colonic mucosa graft urethroplasty is a
      feasible procedure for long, complex anterior urethral strictures. The technique
      may be considered for urethral reconstruction when more conventional procedures
      have failed.

PMID- 14665881
TI  - Tube-onlay-tube tunica vaginalis flap for proximal primary and reoperative adult
      hypospadias.
AB  - PURPOSE: We describe the surgical technique of and report the results in the
      first 20 patients who underwent combined onlay-tube construction of a tunica
      vaginalis flap. MATERIALS AND METHODS: We repaired 20 cases of proximal primary
      (8) and repeat (12), adult hypospadias using a tube-onlay in 4, an onlay-tube in
      3, a tube-onlay-tube in 9 and an onlay-tube-onlay in 4. In 15 patients
      contralateral tunica vaginalis was used as a blanket wrap. Three to 6 months
      postoperatively after obtaining informed consent retrograde urethrography,
      cystourethroscopy, uroflowmetry and urethral biopsy were done in 20, 17, 10 and
      13 patients, respectively. RESULTS: No fistula or diverticulum developed.
      Complications occurred in 3 patients (15%), including urethral stricture, meatal
      stenosis and urethral stricture, and meatal regression and urethral stricture in
      1 each. All strictures occurred in the distal urethra in reoperative cases. At
      long-term followup there was no recurrent stricture or meatal stenosis after
      internal urethrotomy and dilation. Urethral biopsy in all 13 patients showed a
      stratified epithelium indistinguishable from native urethra. The reasons for
      delayed presentation include perceiving hypospadias as a normal variation
      (paribor or cut by angels), losing hope for a cure after multiple failed repairs,
      being told by urologists that repair is futile and pressure by wives for cosmetic
      or fertility reasons. CONCLUSIONS: The place of tunica vaginalis in hypospadias
      surgery is more than coverage for urethroplasty. It can be successfully used for
      substitution urethroplasty. As an extension to the principles of the onlay flap
      and the concept of urethral plate preservation, combined onlay-tube constructions
      of tunica vaginalis, including a tube-onlay-tube flap, are successfully
      applicable to proximal hypospadias, especially in reoperative cases.
      Urothelialization of the tunica vaginalis occurs within months of surgery.

PMID- 14665882
TI  - Experience with coapted gastric tube outlet and composite gastrointestinal
      reservoir for continent cutaneous urinary diversion.
AB  - PURPOSE: Established techniques for urinary diversion are not ideal for certain
      patients such as those with extensive pelvic irradiation, metabolic acidosis,
      short bowel syndrome or renal insufficiency. In a multi-institutional study a
      gastrointestinal reservoir was previously found to provide metabolic balance in
      such patients. We used a coapted gastric tube as the continent outlet in patients
      undergoing gastrointestinal urinary diversion. We evaluate the long-term
      functional results of the gastric tube to provide continence and report our long
      term followup results. MATERIALS AND METHODS: A composite reservoir was
      constructed from gastric and transverse colon or ileal segments. In addition, a
      gastric strip, in continuity with the gastric segment of the composite reservoir,
      was tubularized and coapted to provide the continence mechanism. RESULTS: A total
      of 19 patients with a gastrointestinal reservoir and coapted gastric tube outlet
      were followed for 24 to 101 months, of whom 18 are continent day and night on
      intermittent catheterization every 3 to 8 hours. Four of 34 ureters (12.5%)
      became obstructed. One patient had significant preoperative renal insufficiency,
      which progressed to end stage renal disease. Another patient had slow progression
      of renal insufficiency. In the remaining 17 patients mean serum creatinine did
      not change significantly while serum chloride and bicarbonate improved or
      remained normal. CONCLUSIONS: A coapted gastric tube functions well as the
      continence mechanism in patients with a gastrointestinal urinary reservoir. We
      also confirm the metabolic advantages of a composite gastrointestinal urinary
      reservoir. Gastrointestinal cutaneous urinary diversion can be an alternative to
      incontinent diversion in select patients who are not suitable for other forms of
      diversion.

PMID- 14665883
TI  - A prospective comparison of 3 diagnostic methods to evaluate ejaculatory duct
      obstruction.
AB  - PURPOSE: Various diagnostic tests are available to evaluate patients with
      ejaculatory duct obstruction (EDO). However, the most accurate diagnostic
      technique, defined as the one that best predicts a successful outcome after
      ejaculatory duct resection, is unclear. We prospectively performed transrectal
      ultrasound (TRUS) and 3 other tests in men with EDO and determined their relative
      value in this diagnosis. MATERIALS AND METHODS: Patients with suspected EDO on
      clinical evaluation that included TRUS proceeded to further intraoperative
      evaluation with duct chromotubation, seminal vesicle aspiration and seminal
      vesiculography. A comparative analysis of findings from each technique was
      performed and the success of subsequent transurethral resection procedures was
      assessed. RESULTS: All 25 patients had evidence of EDO on diagnostic TRUS, a
      finding that merited further evaluation with other modalities. However, TRUS
      findings correlated poorly with those of the other diagnostic tests. Obstruction
      on TRUS was confirmed in only 52%, 48% and 36% of vesiculography, seminal vesicle
      aspiration and duct chromotubation studies, respectively. A better correlation
      was observed between the dynamic tests of duct chromotubation and seminal
      vesiculography. Based on all diagnostic tests only 12 patients (48%) proceeded to
      duct resection, of whom 10 (83%) showed significant improvement in semen analysis
      parameters or clinical symptoms after the procedure. CONCLUSIONS: A comparative
      analysis of 4 diagnostic techniques suggests that TRUS alone has poor specificity
      for EDO evaluation. Incorporating dynamic tests into the algorithm of EDO
      diagnosis may decrease unnecessary duct resection procedures and improve the
      success of the resection procedures that are indicated.

PMID- 14665884
TI  - Multiphasic helical computerized tomography for the assessment of microscopic
      hematuria: a prospective study.
AB  - PURPOSE: We evaluated multiphasic helical computed tomography for the detection
      and characterization of lesions responsible for hematuria not diagnosed on prior
      urological surveillance studies. MATERIALS AND METHODS: A total of 393 men and
      207 women with recurrent microscopic hematuria but negative urological
      surveillance studies were examined at 4 participating institutions by multiphasic
      helical computerized tomography, consisting of pre-enhancement, arterial
      corticomedullary, parenchymal and excretory phase sequences generating 2 to 5 mm
      slices through the kidney and lower pelvis. RESULTS: The cause of microscopic
      hematuria was established in 256 of 600 patients with prior negative urological
      surveillance examinations with 0.91 sensitivity and 0.94 specificity. The
      diagnosis was correct in all subsequently proven cases of calculous and renal
      vascular disease. A total of 67 of 70 inflammatory kidney lesions, 24 of 25 renal
      neoplasms, 15 of 16 bladder neoplasms, 27 of 35 inflammatory bladder conditions
      and 21 of 23 ureteral lesions were also correctly diagnosed. The diagnosis of
      renal medullary and papillary necrosis, and neoplastic lesions of the kidney and
      bladder allowed the early institution of medical therapy or appropriate surgery.
      CONCLUSIONS: Multiphasic helical computerized tomography diagnosed lesions
      responsible for microhematuria in 42.6% of 600 patients with negative urological
      surveillance examinations. This relatively low cost and low co-morbidity
      examination is advocated for patients with negative urological surveillance
      examinations or even as a first examination.

PMID- 14665885
TI  - Closed suction or penrose drainage after partial nephrectomy: does it matter?
AB  - PURPOSE: Prospective studies in the general surgery literature have shown fewer
      wound related complications with closed suction drainage than with open passive
      drainage. Nevertheless, some urologists avoid closed suction drains after partial
      nephrectomy mainly because of a theoretical increased risk of a prolonged urinary
      leak or delayed hemorrhage. MATERIALS AND METHODS: We reviewed the records of 184
      patients who underwent 197 consecutive partial nephrectomies at our institution.
      Closed suction or open passive (Penrose) drainage was used based on surgeon
      preference. Drain type was compared with duration of use and the incidence of
      relevant complications. RESULTS: A Penrose drain was used in 37.6% (74 of 197) of
      partial nephrectomies and a closed suction drain was used in 62.4% (123).
      Clinical characteristics were equivalent between both groups, including age, body
      mass index, tumor size (mean 3.1 cm), number of renal tumors excised, estimated
      blood loss and operative time. There was no statistically significant difference
      in the duration of drainage between the Penrose group (mean 7.1 days) and the
      closed suction group (7.8 days). While we found variation in the incidence of
      relevant complications by drain type, none of these differences was statistically
      significant. Complications included prolonged urinary drainage in 7.6% of cases
      (8.9% closed suction, 5.4% Penrose), wound infection or perinephric abscess in
      3.6% (2.4% closed suction, 5.4% Penrose) and delayed hemorrhage in 1.5% (2.4%
      closed suction, 0 Penrose). CONCLUSIONS: No statistically significant differences
      in postoperative morbidity were observed between the use of closed suction or
      Penrose retroperitoneal drains after partial nephrectomy.

PMID- 14665886
TI  - Randomized trial of lidocaine vs lidocaine/bupivacaine periprostatic injection on
      longitudinal pain scores after prostate biopsy.
AB  - PURPOSE: Periprostatic lidocaine reduces immediate post-prostate biopsy pain but
      still many men will not consent to re-biopsy. We performed a randomized study to
      assess whether adding long acting local anesthesia to a short acting agent would
      further reduce pain. MATERIALS AND METHODS: A total of 300 men undergoing
      transrectal ultrasound guided prostate biopsy were sequentially randomized to
      receive either short acting local lidocaine (lid) or short and long acting
      lidocaine and bupivacaine (lid/bup). A 7-day questionnaire was used to study
      daily pain (10-point visual analog score), bleeding (hematuria, PR bleeding,
      hematospermia), visits to the family doctor and analgesic use, and whether they
      would agree to future re-biopsy. RESULTS: Of the 256 questionnaires returned 250
      were suitable for analysis. Cross-sectional comparison showed no intergroup
      differences in mean pain scores immediately after biopsy (2.24, 95% CI 1.94-2.5
      vs 2.61, 95% CI 2.3-2.9, p = 0.88 in lid and lid/bup groups, respectively). There
      was a significant rebound in visual analog scale at 1 hour in the lid group but
      not in the lid/bup group (+ 0.9 vs + 0.09, p = 0.0006). Longitudinal analysis
      showed the global pain experience after lid/bup was better compared to lidocaine
      alone, with significantly less pain every subsequent day (p = 0.0006 to 0.002).
      No difference was seen in morbidity, analgesia usage or number refusing future re
      biopsy (9.6% vs 9.8%). CONCLUSIONS: Long and short acting local anesthetics
      together significantly attenuate the 1-hour rebound increase in pain scores seen
      after short acting anesthesia alone. Improved pain scores were sustained during
      the subsequent week and we advocate routine combination use for transrectal
      ultrasound guided prostate biopsy.

PMID- 14665887
TI  - Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor
      hyperreflexia in spinal cord injured patients: a double-blind, randomized,
      controlled study.
AB  - PURPOSE: Chemical defunctionalization of C-fiber bladder afferents with
      intravesical vanilloids such as capsaicin (CAP) or resiniferatoxin (RTX) improves
      detrusor hyperreflexia in humans and animals. The little existing data comparing
      the efficacy and tolerance of these 2 vanilloid agents seem to favor RTX in 10%
      alcohol over CAP, which is usually diluted in 30% alcohol. We compared the
      efficacy and tolerability of the 2 vanilloid agonists in what to our knowledge is
      the first randomized, controlled study comparing nonalcohol CAP vs RTX in 10%
      alcohol in neurogenic patients with detrusor hyperreflexia. MATERIALS AND
      METHODS: This single center, randomized, double-blind, parallel groups study
      included 39 spinal cord injured adults with detrusor hyperreflexia. On day 0
      patients were randomized to receive 1, 100 ml intravesical instillation of 100
      nMol/l RTX diluted in 10% ethanol or 1 mmol/l CAP diluted in glucidic solvent.
      Efficacy (voiding chart and cystomanometry) and tolerability were evaluated
      during a 3-month followup. RESULTS: On day 30 clinical and urodynamical
      improvement was found in 78% and 83% of patients with CAP vs 80% and 60% with
      RTX, respectively, without a significant difference between the 2 treated groups.
      The benefit remained in two-thirds of the 2 groups on day 90. There were no
      significant differences in regard to the incidence, nature or duration of side
      effects in CAP vs RTX treated patients. CONCLUSIONS: Our results strongly argue
      for the importance of accounting for the role of vanilloid solute when
      interpreting the efficacy and tolerance of vesical vanilloid instillation in
      detrusor hyperreflexia cases. They suggest that a glucidic solute is a valuable
      solvent for vanilloid instillation.

PMID- 14665888
TI  - Evaluation of painful hydronephrosis in pregnancy: magnetic resonance urographic
      patterns in physiological dilatation versus calculous obstruction.
AB  - PURPOSE: We evaluated magnetic resonance urography (MRU) appearances in
      symptomatic hydronephrosis in pregnancy and compared urographic patterns in
      physiological and calculous disease. MATERIALS AND METHODS: A total of 24
      consecutive pregnant women with symptomatic hydronephrosis underwent MRU,
      comprising an overview fast T2-weighted examination of the abdomen and pelvis,
      and thick slab, heavily T2-weighted MRU images, followed by focused, high
      resolution T2-weighted sequences obtained in an axial and coronal oblique plane
      through the level of ureteral caliber change. RESULTS: Of these 24 pregnant women
      15 were found to have physiological hydronephrosis, 7 had calculous disease and 2
      had preexisting urinary anomalies. MRU findings in physiological hydronephrosis
      cases were extrinsic compression of the middle third of the ureter, no filling
      defect and a collapsed ureter below it. Obstruction by ureteral calculi was seen
      at points of ureteral narrowing in the ureter, that is at the vesicoureteral
      junction in 2 cases, in the compressed mid ureter in 3 and at the pelviureteral
      junction in 1. Nonobstructive renal calculi were seen in another patient. Calculi
      presented throughout pregnancy but physiological hydronephrosis presented only in
      the late second and third trimesters. With distal calculi the MRU appearance was
      the double kink sign with constriction at the pelvic brim and the vesicoureteral
      junction with a standing column of urine in the pelvic ureter. There was renal
      edema and perirenal extravasation. Small calculi were only identified using high
      resolution T2-weighted magnetic resonance imaging. CONCLUSIONS: MRU is a valuable
      and well tolerated investigation for evaluating painful hydronephrosis in
      pregnancy. There are characteristic and differing urographic appearances in
      physiological and calculous obstruction.

PMID- 14665889
TI  - Short-term outcome analysis of total pelvic reconstruction with mesh: the vaginal
      approach.
AB  - PURPOSE: We describe our experience with transvaginal total pelvic reconstruction
      using a mesh with 4-point fixation for patients with genitourinary prolapse with
      or without stress urinary incontinence. MATERIALS AND METHODS: A total of 29
      consecutive patients who underwent sacrospinous fixation using mesh material
      since March 1999 for genitourinary prolapse were analyzed retrospectively. In all
      patients defect specific repair was done, including hysterectomy (in 13). For
      isolated vault prolapse a rectangular mesh was interposed between the peritoneum
      and vaginal vault, with each corner anchored to the sacrospinous ligament using a
      suture-capturing device. For vault prolapse associated with anterior vaginal wall
      prolapse an "H" shaped, 1-piece sling was used to support both entities.
      Additionally, posterior and perineal repairs were done through separate incisions
      if needed. RESULTS: Of the 29 patients 19 (65.5%), 7 (26.92%) and 11 (39.29%) had
      associated symptoms of stress urinary incontinence, urgency and frequency,
      respectively, and 79.31% had associated anterior and 44.8% had associated
      posterior prolapse. Average operative time was 175.6 minutes, blood loss was 340
      cc and hospital stay was 2.46 days. Early adverse events following the procedure
      were perineal pain, vaginal discharge and irritative voiding symptoms. At 6 month
      followup (mean 25.14 months) mild constipation and dyspareunia were encountered
      in a small subset of patients. Two patients (6.89%) have genital prolapse
      recurrence and none has reported erosion or nonhealing to date. CONCLUSIONS:
      Transvaginal technique of 4-point vaginal vault fixation using mesh is a safe and
      effective procedure at 2 years.

PMID- 14665890
TI  - Anterior vaginal wall hammock with fascia lata for the correction of stage 2 or
      greater anterior vaginal compartment relaxation.
AB  - PURPOSE: We determined the efficacy of the anterior vaginal wall hammock (AVWH)
      using fascia lata for the correction of anterior vaginal compartment relaxation.
      MATERIALS AND METHODS: A total of 58 patients with stage 2 or greater anterior
      vaginal compartment relaxation underwent an AVWH procedure with autologous or
      allograft fascia lata from June 1998 to March 2001. Patients were evaluated
      preoperatively with a history and pelvic organ prolapse quantitative examination.
      Postoperatively patients were evaluated at 6 weeks, 6 months and yearly
      thereafter with pelvic organ prolapse quantitative staging of the anterior,
      middle and posterior compartments. Objective cure was defined as stage 0 or 1
      relaxation. Subjective cure was defined as no symptoms of pelvic pressure or a
      vaginal bulge. RESULTS: Of the 69 (89%) patients who underwent surgery 58 were
      available for followup. Median age of the population was 61.9 years and median
      followup was 24.7 months (range 12 to 57). There were 11 objective failures (19%)
      in the anterior compartment, of which 1 (2%) was symptomatic. Two patients (4%)
      had enteroceles that required surgical correction. Of the patients 16 (28%) had
      new onset or worsening stage 2 posterior relaxation at a median of 15.2 months
      postoperatively, including 7 (12%) who were symptomatic and underwent subsequent
      repair. CONCLUSION: The AVWH procedure with fascia lata is safe and effective for
      correcting stage 2 or greater anterior compartment relaxation. The whole pelvic
      floor must be evaluated and repaired to minimize the progression of prolapse of
      the middle and posterior compartments.

PMID- 14665891
TI  - 8-ply small intestinal submucosa tension-free sling: spectrum of postoperative
      inflammation.
AB  - PURPOSE: We report a series of postoperative inflammatory reactions of a tension
      free pubourethral sling procedure using an 8-ply small intestinal submucosa (SIS)
      and review the literature regarding inflammatory reactions with this material in
      genitourinary reconstruction. MATERIALS AND METHODS: Between August 2002 and June
      2003, 6 of 10 patients treated for stress urinary incontinence with 8-ply SIS had
      postoperative inflammatory reactions. Patients underwent a thorough evaluation,
      including history, physical examination and urodynamic studies, before surgical
      intervention. RESULTS: All patients presented with induration and erythema at the
      abdominal incision site(s) and pain 10 to 39 days postoperatively. Pelvic
      examinations were negative. In 3 patients the inflammatory reaction resolved with
      minimal or no intervention. Incision and drainage of a sterile abscess were
      required in 1 patient. Despite 7 days of prophylactic postoperative antibiotics
      and anti-inflammatory drugs, 2 patients had delayed inflammatory reactions. One
      patient had resolution with conservative treatment, while the other had an
      abscess that spontaneously drained. With short-term followup (mean 7 months,
      range 4 to 10), 8 patients are dry, 1 is improved and 1 is incontinent.
      CONCLUSIONS: While the results with the 8-ply SIS tension-free sling in the short
      term are encouraging, the additional morbidity is alarming and caution is
      warranted. It is essential that patients be made aware of potential risks and
      possible delayed presentation of morbidity with the use of this material. The
      human to 8-ply SIS interaction needs further investigation to ensure that long
      term safety and efficacy will not be jeopardized. Until then we will continue to
      use other sling materials.

PMID- 14665892
TI  - Large post-hysterectomy and post-radiation vesicovaginal fistulas: repair by
      ileocystoplasty.
AB  - PURPOSE: We devised a technique for simultaneous closure of large post
      hysterectomy and post-radiation vesicovaginal fistulas, and augmentation of the
      concomitant shrunken bladder by ileocystoplasty as a 1-step procedure. MATERIALS
      AND METHODS: Between 1989 and 2000, 4 patients with large vesicovaginal fistulas
      after radical hysterectomy and radiotherapy for spinocellular cancer of the
      uterine cervix underwent fistula repair according to the technique described. The
      premise of utmost importance in the proposed technique is a healthy and not
      radiation damaged distal ileum. RESULTS: Fistula closure was achieved in 3
      patients, while in 1 a 3 mm residual fistula was repaired 5 years later by a
      Martius skin flap. In all patients the augmented bladder allowed good quality of
      life with spontaneous voiding, and daytime and nighttime continence. CONCLUSIONS:
      The technique described seems to have certain advantages. Wide dissection of the
      bladder from the vagina and pelvic walls is avoided. The bladder defect is closed
      with a well vascularized ileal segment. Bladder capacity is enlarged
      simultaneously with good functional results. The procedure can be adapted to
      cases with concomitant damaged distal ureters.

PMID- 14665893
TI  - Local urethral recurrence after radical cystectomy and orthotopic bladder
      substitution in women: a prospective study.
AB  - PURPOSE: We prospectively studied the pathological outcome and incidence of
      urethral recurrence after radical cystectomy and orthotopic bladder substitution
      in women. MATERIALS AND METHODS: Between January 1995 and December 2001, 145
      women with a mean age of 50 +/- 8.5 years underwent standard radical cystectomy
      and orthotopic substitution for bladder cancer. Histopathological examination of
      the cystectomy specimens was assessed by a single pathologist. Clinically evident
      pelvic lymphadenopathy, bladder neck and/or vaginal wall involvement, or positive
      intraoperative frozen section from the urethra were considered contraindications.
      RESULTS: One patient died postoperatively of a massive pulmonary embolism.
      Followup was 12 to 97 months (mean 36, median 55.8). Pathological stage was P1,
      P2 (superficial muscle invasion), P3a (deep muscle invasion), P3b (perivesical
      fat infiltration) and P4a in 12, 29, 56, 44 and 4 patients, respectively. Grade
      was G1 in 61 patients, G2 in 62 and G3 in 22. Lymph nodes were positive in 28
      cases and negative in 117. Histopathology of the trigone revealed carcinoma in
      situ in 11 cases and squamous metaplasia in 7, while results were free of disease
      in the remainder. At followup isolated urethral recurrence developed in 2
      patients (1.4%), in whom definitive pathological findings showed P3a N1 (positive
      iliac lymph nodes) M0, grade 2 squamous cell carcinoma in 1 and P3b N0M0 tumor
      associated with trigonal carcinoma in situ in 1. Local pelvic recurrence
      developed in 18 patients, distant metastasis developed in 6 and the 2 conditions
      developed in 10. Oncological failure positively correlated with high stage, high
      grade and positive lymph nodes. CONCLUSIONS: The rate of urethral recurrence
      after radical cystectomy and orthotopic bladder substitution in women is low and
      acceptable and, thus, it justifies the continued performance of this type of
      diversion. Proper selection of cases is mandatory. Close followup for oncological
      failure in this group of patients after cystectomy is necessary.

PMID- 14665894
TI  - Low agreement between previous physician diagnosed prostatitis and national
      institutes of health chronic prostatitis symptom index pain measures.
AB  - PURPOSE: We evaluate the agreement between self-reported physician diagnosed
      prostatitis and pain questions from the National Institutes of Health Chronic
      Prostatitis Symptom Index (CPSI). MATERIALS AND METHODS: A randomly selected
      cohort of white men 47 to 90 years old from Olmsted County, Minnesota completed a
      study questionnaire on a history of physician diagnosed prostatitis in the
      preceding 2 years, including the CPSI questions. The medical records were also
      reviewed for physician diagnosis of chronic prostatitis during the preceding 10
      years. RESULTS: Of 1,543 men 27 (1.7%) reported a physician diagnosis of
      prostatitis in the preceding 2 years. There were strong associations between self
      reported prostatitis and pain at the tip of the penis (OR 6.3, 95% CI 1.4, 28.5),
      ejaculatory (5.9, CI 1.3, 26.6) and testicular (3.6, 1.2, 10.8) pain. The chance
      corrected agreement between self-reported prostatitis and pain symptoms was low
      at 0.01 (pubic pain) to 0.07 (pain at the tip of the penis, ejaculatory pain and
      testicular pain). Agreement in positive responses was also low at 3.7% (perineal
      pain) to 8% (pain at the tip of the penis, ejaculatory pain and testicular pain).
      The predictive value of the modified total CPSI score for prostatitis was 0.67,
      which was better than chance (0.5). Associations based on medical record
      ascertainment of prostatitis during followup were weak, and the area under the
      curve was 0.57, which was no better than chance. CONCLUSIONS: These findings
      demonstrate low agreement between CPSI-like pain measures and self-reported
      physician diagnosed prostatitis. The stronger associations between pain symptoms
      and self-reported diagnosed prostatitis, and the moderate predictive ability of
      the modified total CPSI score measures for self-reported prostatitis compared to
      medical record ascertainment demonstrate the sensitivity of the CPSI to prevalent
      symptoms. Thus, the tool may be best used to evaluate the severity of current
      symptoms rather than to assess the presence or absence of prostatitis.

PMID- 14665895
TI  - A prospective, 1-year trial using saw palmetto versus finasteride in the
      treatment of category III prostatitis/chronic pelvic pain syndrome.
AB  - PURPOSE: This study was designed to assess the safety and efficacy of saw
      palmetto or finasteride in men with category III prostatitis/chronic pelvic pain
      syndrome (CP/CPPS). MATERIALS AND METHODS: A prospective, randomized, open label,
      1-year study was designed to assess the safety and efficacy of saw palmetto and
      finasteride in the treatment of men diagnosed with CP/CPPS. Patients were
      randomized to finasteride (5 mg once daily) or saw palmetto (325 mg daily) for 1
      year. Patients were evaluated using the National Institutes of Health Chronic
      Prostatitis Symptom Index, individual domains (pain, urinary symptoms, quality of
      life and mean pain score) and the American Urological Association Symptom Score
      at baseline, 3, 6 and 12 months. RESULTS: A total of 64 consecutive men 24 to 58
      years old (mean age 43.2) with a diagnosis of CP/CPPS were equally randomized to
      the 2 treatment arms. All 64 men had previously received antibiotics (duration of
      3 to 93 weeks), 52 (82%) had been on alpha-blockade. There were 61, 57 and 56
      patients evaluable at 3, 6 and 12 months, respectively. At 1 year mean total
      National Institutes of Health Chronic Prostatitis Symptom Index score decreased
      from 23.9 to 18.1 in the finasteride group (p <0.003), and from 24.7 to 24.6 in
      the saw palmetto arm (p = 0.41). In the finasteride arm the quality of life and
      pain domains were significantly improved at 1 year; however, urination was not.
      Adverse events included headache (3 cases) in the saw palmetto group and
      decreased libido (2 cases) in the finasteride group. At the end of the trial 13
      of 32 (41%) and 21 of 32 (66%) opted to continue saw palmetto and finasteride,
      respectively. CONCLUSIONS: CP/CPPS treated with saw palmetto had no appreciable
      long-term improvement. In contrast, patients treated with finasteride had
      significant and durable improvement in all various parameters except voiding.
      Further studies are warranted to ascertain the mechanism and reproducibility of
      these effects in a placebo controlled trial.

PMID- 14665896
TI  - Safer transurethral resection of the prostate: coagulating intermittent cutting
      reduces hemostatic complications.
AB  - PURPOSE: Transurethral resection of the prostate (TURP) is still the gold
      standard for the surgical treatment of symptomatic benign prostatic hyperplasia.
      However, the associated morbidity and blood loss remain concerns. A coagulating
      intermittent cutting (CIC) device with constant voltage pulses and controlled
      pulse intervals was recently developed. The impact of CIC on bleeding and blood
      transfusion rates as well as the occurrence of the TUR syndrome were
      investigated. MATERIALS AND METHODS: From January 2000 to July 2002, 271
      consecutive patients with symptomatic benign prostatic hyperplasia underwent TURP
      with the CIC device. In addition to blood transfusion rates, serum hemoglobin and
      electrolytes were determined in all patients immediately before and after TURP.
      RESULTS: The mortality rate in the 271 patients subjected to TURP was 0.0%. Mean
      decrease in hemoglobin after TURP was 1.08 mg/dl. Intraoperative and
      postoperative blood transfusions were required in 7 patients (2.6%), and clinical
      signs of the transurethral resection syndrome were noted in 1.1% of patients.
      CONCLUSIONS: Coagulating intermittent cutting dramatically improves the safety of
      TURP by decreasing intraoperative and postoperative blood loss, and the rate of
      blood transfusions. With this blood sparing device we anticipate a lower
      incidence of hemostatic complications from TURP.

PMID- 14665897
TI  - Concomitant use of sildenafil and a vacuum entrapment device for the treatment of
      erectile dysfunction.
AB  - PURPOSE: Men not entirely satisfied with erectile function after separate use of
      sildenafil or a vacuum entrapment device (VED) are usually given more invasive
      alternatives. This prospective study was designed to evaluate the efficacy of
      concomitant use of sildenafil and a vacuum entrapment device in men not satisfied
      with erectile function while using each of these treatment modalities separately.
      MATERIALS AND METHODS: A total of 161 patients suffering from erectile
      dysfunction for at least 6 months were evaluated and treated with 100 mg
      sildenafil and a VED each as monotherapy. The 41 patients not satisfied with
      erectile function while using either modality alone were treated with concomitant
      use of sildenafil and a VED. The International Index of Erectile Function and
      global assessment question about satisfaction from treatment were used to
      evaluate satisfaction before and after each treatment. RESULTS: All 41 patients
      stated on the global assessment question that they had a greater level of
      satisfaction with the results of combined treatment than with each treatment
      alone (p <0.0001). Older (age greater than 60 years) participants reported better
      overall satisfaction. There was no correlation between treatment outcome and
      erectile dysfunction etiology or between satisfaction from treatments and the
      order in which they were given and the pretreatment scores for the International
      Index of Erectile Function domains. CONCLUSIONS: Combined use of sildenafil and a
      VED may be offered to patients not satisfied when either treatment is used alone.

PMID- 14665898
TI  - Questionable efficacy of extracorporeal shock wave therapy for Peyronie's
      disease: results of a prospective approach.
AB  - PURPOSE: Extracorporeal shock wave therapy (ESWT) for Peyronie's disease is still
      a topic of debate. We evaluated the effects of ESWT in a large series of patients
      with Peyronie's disease via a prospective approach. MATERIALS AND METHODS: In a
      prospective study 114 patients with Peyronie's disease were treated with ESWT.
      Baseline and followup examinations included ultrasound, and measurement of plaque
      size and curvature. Symptomatology was evaluated based on a standardized
      interview. A Minilith SL1 (Storz Medical AG, Kreuzlingen, Switzerland)
      lithotriptor was used with 4,000 shock waves at a maximum energy level of 0.17
      mJ/mm2 applied per session. RESULTS: A total of 96 patients were available for
      followup. Considering the total study group no significant changes in penile
      curvature, plaque size or sexual function were observed despite significant
      improvements in patients with a curvature of 31 to 60 degrees. Penile pain ceased
      in 76% of the affected patients. CONCLUSIONS: According to our data ESWT does not
      appear to be significantly effective for decreasing penile curvature and plaque
      size or improving sexual function in the total population of patients with
      Peyronie's disease despite improvements in individuals. Penile pain seems to
      resolve earlier than during the natural course. Regarding the results of this
      study and previous reports with exact documentation of the clinical findings it
      can be concluded that ESWT cannot be recommended as a standard procedure for
      Peyronie's disease. To evaluate the exact efficacy of ESWT a controlled, single
      blind, multicenter study with exact documentation of symptoms is urgently
      required.

PMID- 14665899
TI  - Initial evaluation of robotic technology for microsurgical vasovasostomy.
AB  - PURPOSE: Conventional microscope assisted vasovasostomy (MAVV) is a technically
      difficult procedure that is most successful in the hands of well-trained
      microsurgeons. Robotics may help surgeons overcome the microsurgical challenges
      of tremor, limited dexterity, miniaturized instrumentation and use of fine
      suture. We determine the feasibility of a robotic assisted vasovasostomy (RAVV)
      and compare performance measures with those of conventional MAVV. MATERIALS AND
      METHODS: One surgeon performed 10 vasovasostomies with a modified 1-layer
      technique and 9-zero suture on fresh human vas specimens using the robot in 5
      RAVV cases and standard microsurgical instrumentation in 5 MAVV cases. Pre
      specified performance measures and adverse haptic events (broken sutures, bent
      needles or loose stitches) were recorded. Patency was evaluated by instilling
      saline through the anastomoses. RESULTS: Mean operating time and number of
      adverse haptic events were higher for RAVV than for MAVV (84 vs 38 minutes, p =
      0.01; 2.4 vs 0.0 events, p = 0.03). The number of needle passes required for the
      6 full-thickness stitches was similar in both groups (16.8 vs 15.2 passes, p =
      0.55). Although no tremor occurred during RAVV, minimal to moderate amounts
      occurred during MAVV. Minimal fatigue was noted for both groups. Patency was
      confirmed in all 10 operations. CONCLUSIONS: Use of RAVV in this human ex vivo
      vas model was feasible. While RAVV took longer to perform and was associated with
      adverse haptic events, elimination of tremor and comparable patency rates suggest
      that it may be a viable surgical alternative for microsurgical vasovasostomy.

PMID- 14665900
TI  - The impact of obstructive interval and sperm granuloma on outcome of vasectomy
      reversal.
AB  - PURPOSE: We studied the impact of the interval from vasectomy to reversal and
      presence of sperm granuloma on outcomes of reversal. MATERIALS AND METHODS: A
      total of 213 microsurgical vasectomy reversals performed by a single surgeon were
      stratified according to obstructive intervals of less than 5 years, 5 to 10
      years, 10 to 15 years and greater than 15 years. The effects of obstructive
      interval on patency and pregnancy rates were assessed using multivariate
      logistical regression. The impact of sperm granuloma on patency and pregnancy was
      assessed using the chi-square test. RESULTS: Patency did not change with
      increasing obstructive intervals as can be seen with 91% patency at less than 5
      years, 88% at 5 to 10 years, 91% at 10 to 15 and 89% at greater than 15 years.
      There was no difference in pregnancy rates (89%, 82% or 86%) at obstructive
      intervals of 0 to 5, 5 to 10 or 10 to 15 years, respectively. Pregnancy rates
      were significantly lower (44%, p <0.05) with obstructive intervals greater than
      15 years. Men with at least unilateral sperm granuloma had patency of 95% vs 78%
      without granulomas, a trend which did not quite reach statistical significance (p
      = 0.07). There was no difference in pregnancy rates with or without granulomas.
      CONCLUSIONS: Vasectomy reversal patency rates are high regardless of time since
      vasectomy. Pregnancy rates are lower more than 15 years after vasectomy. Sperm
      granuloma had a favorable impact on patency. Our data indicate that for
      obstructive intervals less than 15 years vasectomy reversal yields much higher
      pregnancy rates than in vitro fertilization and intracytoplasmic sperm injection,
      and that even for intervals greater than 15 years reversal outcomes equal or
      exceed those of in vitro fertilization and intracytoplasmic sperm injection.

PMID- 14665901
TI  - The relationship between intravasal sperm quality and patency rates after
      vasovasostomy.
AB  - PURPOSE: Most surgeons examine the intravasal fluid at vasectomy reversal.
      Vasovasostomy is performed when sperm are identified in the intravasal fluid or
      when sperm are absent but the fluid is copious and clear. When sperm are absent
      and the intravasal fluid is not copious and clear, vasoepididymostomy is often
      performed. Frequently the intravasal fluid contains only fragments of sperm. This
      study examines patency rates after microsurgical vasovasostomy as a function of
      the quality of sperm in the intravasal fluid. MATERIALS AND METHODS: The records
      of patients who had undergone microsurgical vasovasostomy were reviewed. The
      intravasal fluid was examined and sperm quality was recorded as no sperm, sperm
      heads, sperm with short tails or whole sperm. Results of postoperative semen
      analyses were recorded. Patency rates and postoperative semen parameters were
      compared. RESULTS: A total of 53 patients satisfied the entrance criteria. Ages
      ranged from 25 to 53 (mean age 39). Mean obstructive interval was 9.9 years
      (range 1 to 20). Overall patency was 98% (52 of 53 cases). Patency rates were 95%
      for the group with sperm heads and 100% for whole sperm, sperm with short tails
      and absent sperm groups. Patency rates did not vary significantly as a function
      of intravasal sperm quality. CONCLUSIONS: Modern microsurgical techniques yield
      excellent patency rates. The presence of sperm parts compared to whole sperm does
      not adversely affect patency rates after vasovasostomy. Vasovasostomy should be
      performed if any sperm parts are identified in the intravasal fluid.

PMID- 14665902
TI  - Vasectomy reversal-predicting outcomes.

PMID- 14665903
TI  - Practice patterns in vasectomy reversal surgery: results of a questionnaire study
      among practicing urologists.
AB  - PURPOSE: Although vasectomy reversal surgery is a common procedure for male
      factor infertility, little is written on the common practice patterns of the
      practicing urologist. We designed a questionnaire to assess the practice patterns
      of community and academic urologists with respect to surgical technique, followup
      care, patient selection and the definition of success. MATERIALS AND METHODS: A
      20-question survey pertaining to vasectomy reversal surgery was mailed to members
      of the Western Section, American Urological Association and to members of the
      Society of Government Service Urologists. Survey results were tabulated in a
      computer data base and statistical analysis was performed. RESULTS: A total of
      1,508 questionnaires were mailed and 622 completed questionnaires were returned.
      Of the respondents 367 (59%) indicated that they perform vasectomy reversals,
      including 29 (8%) who were fellowship trained in infertility, 86 (23%) who were
      affiliated with residency training and 252 (69%) who practiced in a community
      setting. As expected, on average fellowship trained urologists performed more
      reversals yearly than academic or community urologists (26.4, 12.2 and 7,
      respectively). Patient selection criteria varied. Of fellowship trained
      urologists 12.5% would elect not to operate if it were greater than 15 years
      since vasectomy compared with 41.9% for academic and 57.1% of community
      urologists. Just more than half (50.2%) of respondents indicated they did not
      recommend routine gynecologic evaluation of the patient partner. When comparing
      fellowship, academic and community practitioners, an operating microscope was
      used in 93%, 65% and 56% of procedures (p <0.001), and vasal fluid was examined
      in 83%, 75% and 67%, respectively. Fellowship trained urologists also used finer
      suture material (p <0.001). An average of 8 anastomotic sutures were placed in 2
      layers but significant differences existed between fellowship trained urologists,
      and their academic and community counterparts. Most urologists (71%) defined
      their success by the presence of sperm in the ejaculate. Only 10.9% of urologists
      recommended sperm cryopreservation at surgery and 90% recommended postoperative
      sexual abstinence (average 3 weeks). All urologists recommended postoperative
      semen analysis done at an average of 3 months. CONCLUSIONS: The practice of
      vasectomy reversal varies among urologists. Differences in surgical technique,
      postoperative care and selection criteria exist. Knowledge of these variations
      may assist practicing urologists to tailor their practice patterns in the
      selection for and performance of vasectomy reversal.

PMID- 14665904
TI  - Do pad tests and voiding diaries affect patient willingness to participate in
      studies of incontinence treatment outcomes?
AB  - PURPOSE: We used the Simplified Urinary Incontinence Outcome Score (SUIOS) to
      retrospectively assess the continence outcomes following 107 consecutive
      autologous rectus fascia pubovaginal sling procedures. This outcome score
      requires completion of a questionnaire, voiding diary and pad test. The voiding
      diary and pad test provide objective data but require a degree of patient effort
      and motivation. We determine if the voiding diary and pad test requirements would
      significantly reduce the rate of followup. MATERIALS AND METHODS: After
      recruitment letters were mailed to all eligible patients, followup telephone
      calls were made to ask them to complete the SUIOS protocol. Those who agreed were
      mailed a packet containing the pre-weighed pads, voiding diary and questionnaire.
      Patients who refused were asked to complete a telephone questionnaire instead.
      Patients were given 1 month to complete and return the study materials. If the
      materials were not returned, repeat telephone reminders were made. If patients
      were unwilling to complete the protocol at this point, they were offered the
      option of completing only the questionnaire by telephone. Treatment outcomes were
      classified according to the SUIOS protocol, and the followup rate for the full
      protocol was compared with that for the questionnaire only responses. RESULTS: Of
      the 107 patients 18 were lost to followup and 10 refused to participate, leaving
      79 (74%) evaluable patients. Mean followup interval was 31 months (range 9 to
      66). Of the 79 women 38 (48%) completed the questionnaire portion but were
      unwilling to complete the voiding diary and pad test. The remaining 41 patients
      (52%) completed the entire protocol. Complete SUIOS scores were 59% cured, 24%
      good response, 10% fair response, 2% poor response and 5% failure. Questionnaire
      response results were similar, with 61% cured, 32% improved and 8% failed.
      CONCLUSIONS: The majority of our patients were unwilling to complete a pad test
      and voiding diary for the purpose of assessing outcomes after anti-incontinence
      surgery. The possible increased accuracy of these outcome measures needs to be
      weighed against the lower followup rate associated with their use.

PMID- 14665905
TI  - Use of a virtual reality simulator for ureteroscopy training.
AB  - PURPOSE: Virtual reality surgical simulators may shorten operative time and
      reduce the potential for iatrogenic injury by providing training outside the
      operating room. We hypothesized that training on a virtual ureteroscopy (VU)
      simulator would allow novice endoscopists to overcome the initial learning curve
      before entering the operating room. MATERIALS AND METHODS: We evaluated 16
      medical students on their ability to perform specific ureteroscopic tasks on a VU
      simulator. The students trained on the simulator for a total of 5 hours over
      multiple sessions using different training modules and then were retested on the
      initial module. Likewise, 16 urology residents with varying degrees of endoscopic
      experience were assessed on the same test module twice, without additional
      simulator training. RESULTS: The students improved task completion time from 17.4
      to 8.7 minutes (p <0.05), while the residents performed the task in 7.6 minutes
      at baseline and 6.7 minutes at the second trial. Stratification of residents by
      years of urology training revealed that the mean completion time for the students
      after training did not differ statistically from that of first year residents who
      had performed a median of 14 clinical ureteroscopies. Furthermore, the subjective
      performance scores of the students were comparable to those of the first year
      residents. CONCLUSIONS: Novice medical students trained on a VU simulator
      improved task completion time by 50% after training, and performed comparably to
      residents who had completed nearly 1 year of urology training. VR training may
      allow beginning urology residents to shorten the initial learning curve
      associated with ureteroscopy training, although this hypothesis requires further
      validation.

PMID- 14665906
TI  - Is cytology required for a hematuria evaluation?
AB  - PURPOSE: The value of urine cytology in evaluating patients with hematuria
      remains controversial. The American Urological Association Best Practice Policy
      on Asymptomatic Microscopic Hematuria recommends cytology only in patients with
      risk factors for transitional cell carcinoma (TCC). This study evaluated how
      often urine cytology yielded supportive or unique information that led to the
      diagnosis of transitional cell carcinoma, the cost of that information and
      whether it would have been obtained using the current best practice policy.
      MATERIALS AND METHODS: Between March 1976 and June 1985, 1,000 sequential
      patients with 1 episode of gross hematuria or microscopic hematuria, defined as
      greater than 3 red blood cells per high power field on 2 of 3 properly collected
      urinalyses, were evaluated according to a standard protocol in a closed panel
      health care system in the state of Hawaii. These records were reviewed to
      determine if urine cytology yielded supportive or unique information that led to
      the diagnosis of TCC. RESULTS: In 4 patients positive urine cytology was the sole
      finding supporting a TCC diagnosis. Urine cytology had a sensitivity of 55% and a
      specificity of 99.3%. The cost of a cytology result that yielded unique
      information was 8,367 US dollars using the 2002 Medicare reimbursement schedule.
      CONCLUSIONS: Urine cytology can have an important role in the evaluation of
      hematuria. The current American Urological Society Best Practice Policy using
      risk factors to select patients for urine cytology would have captured the 4
      patients for whom cytology was the key to diagnosis. Urine cytology was
      comparable to excretory urography, creatinine and cystoscopy in terms of cost
      analysis.

PMID- 14665907
TI  - A simple way to take pictures during endoscopic procedures.
AB  - PURPOSE: We describe a new method of taking pictures from endoscopic images using
      a digital photo camera coupled to the endoscopic lens without an adapter.
      MATERIALS AND METHODS: We used a digital camera with 3.3 megapixel resolution and
      6 x optical zoom. The camera was coupled to the endoscopic lens with no special
      adapter. The image was accompanied through the LCD (liquid crystal display)
      visor, and the picture was taken with the flash button on and with no macro
      resource. The image was then enlarged by optical and digital zoom before being
      easily stored in photo files at the personal computer. RESULTS: The quality of
      the photos obtained by this method was at least similar to that of traditional
      photos, and the data were promptly stored. CONCLUSIONS: We describe a simple
      method of taking pictures from endoscopic images with the additional advantage of
      a facility to edit and store the photographs.

PMID- 14665908
TI  - Reconstruction of extensive upper ureteral damage.
AB  - PURPOSE: Injuries of the ureter are associated with serious surgical
      complications. Injury to the lumbar (upper) part of the ureter is rare, and
      reconstruction may pose considerable surgical challenges. A technique is
      described that proved useful reconstruction of upper ureteral damage. MATERIALS
      AND METHODS: Reconstruction surgery for a ureterocutaneous fistula was required
      as a result of earlier removal of a retroperitoneal tumor. The Heineke-Mikulicz
      maneuver was used to bridge a gap between the ureteral edges. RESULTS: Ureteral
      continuity was achieved and the need for other more morbid measures was avoided.
      CONCLUSIONS: This maneuver is recommended for ureteral reconstruction as a valid
      additional technique in the urological armamentarium.

PMID- 14665909
TI  - Spontaneous neonatal regression of prenatally detected renal cysts in autosomal
      dominant polycystic kidney disease.

PMID- 14665910
TI  - Open conversion from laparoscopic nephrectomy: slippage of surgical clips
      ligating the renal artery affected by atherosclerosis.

PMID- 14665911
TI  - The fractured flexible ureteroscope with locked deflection.

PMID- 14665912
TI  - Laparoscopic resection of retroperitoneal venous hemangioma.

PMID- 14665913
TI  - Development of a bladder stone following a tension-free vaginal tape
      intervention.

PMID- 14665914
TI  - Primary renal carcinoid tumor.

PMID- 14665915
TI  - Renal cell carcinoma in horseshoe kidney with vena caval involvement.

PMID- 14665916
TI  - Intravesical colonic pseudotumor.

PMID- 14665917
TI  - Squamous cell carcinoma of the penis following penile trauma.

PMID- 14665918
TI  - Recurrent paratesticular myxoid liposarcoma in a young man.

PMID- 14665919
TI  - Profound anemia from duodenal invasion of metastatic testicular seminoma.

PMID- 14665920
TI  - Disseminated intravascular coagulation following transrectal ultrasound guided
      prostate biopsy.

PMID- 14665921
TI  - Self-expanding metallic stent placement for renal artery dissection due to blunt
      trauma.

PMID- 14665922
TI  - Aortic injury during initial blunt trocar laparoscopic access for renal surgery.

PMID- 14665923
TI  - Large urethral diverticulum presenting as a scrotal mass: urethral reconstruction
      with ventral onlay buccal mucosa.

PMID- 14665924
TI  - Severe hyperkalemia related to excessive tomato juice ingestion in presence of
      neobladder.

PMID- 14665925
TI  - Pyoderma vegetans of the penis.

PMID- 14665926
TI  - Secondary amyloidosis as an unusual cause of ureteral obstruction.

PMID- 14665927
TI  - Female urethral fibroepithelial polyp with stricture.

PMID- 14665928
TI  - Long-term cryopreserved semen results in a live birth 12 years later.

PMID- 14665929
TI  - Re: Intraoperative nerve stimulation with measurement of urethral sphincter
      pressure changes during radical retropubic prostatectomy: a feasibility study. C.
      P. Nelson, J. E. Montie, E. J. McGuire, G. Wedemeyer and J.T. Wei. J Urol, 169:
      2225-2228, 2003.

PMID- 14665930
TI  - Re: A prospective study measuring penile length in men treated with radical
      prostatectomy for prostate cancer. M. Savoie, S. S. Kim and M. S. Soloway. J
      Urol, 169: 1462-1464, 2003.

PMID- 14665931
TI  - Re: Experiences learned in the successful establishment of a nonheart beating
      donor program for renal transplantation. D. Talbot, B. K. Shelton. P.E. Buckley
      and M. A. Gok. J Urol, 170: 1088-1092, 2003.

PMID- 14665932
TI  - Laparoscopic removal of mullerian duct remnants in boys.
AB  - PURPOSE: Mullerian duct remnants (MDRs) are present in a male
      pseudohermaphroditic form characterized by failure of the mullerian duct to
      regress due to insufficient production or peripheral action of mullerian
      inhibiting substance. The MDR can be asymptomatic but it often results in
      infections, stones and voiding troubles. Furthermore, it may develop into a
      neoplasm. Therefore, surgery is mandatory for large MDRs and symptomatic
      patients. Laparoscopic removal is described. MATERIALS AND METHODS: Six males
      were treated from February 1998 to February 2003. Age at surgery was between 3
      and 18 years (mean 8.6). All patients showed severe hypospadias and 2 had mixed
      gonadal dysgenesis with ambiguous genitalia. Three patients presented with
      urogenital infections and all had a large MDR. Laparoscopic procedures, which
      were preceded by cystoscopy, were performed using a 10 mm umbilical trocar for
      the camera and 3, 5 mm trocars for instruments placed in the suprapubic region
      and iliac fossa bilaterally. The remnants were ligated with endoscopic loops or
      an endoscopic GIA stapler and cut. RESULTS: Mean operative time was 2 hours. We
      noted no complications. In 2 cases there was deferential ectopia and in another
      of mixed gonadal dysgenesis bilateral gonadectomy was performed because of the
      risk of degeneration. Feeding started on postoperative day 1 and the patients
      were discharged home on day 5. After a followup of 8 months to 4 years all boys
      were healthy. CONCLUSIONS: Multiple approaches are used in traditional surgery,
      often leading to complications. Laparoscopy improves the view, decreases surgical
      risk and operative time, avoids large scars and allows more rapid hospital
      discharge.

PMID- 14665933
TI  - Laparoscopic excision of a seminal vesicle cyst in a child.

PMID- 14665934
TI  - Laparoscopic assisted reconstructive surgery: a 7-year experience.
AB  - PURPOSE: Laparoscopic assisted surgery results in an improved cosmetic appearance
      by allowing complex reconstruction without a midline upper abdominal incision. We
      report technique and outcomes in patients undergoing laparoscopic assisted
      reconstruction during a 7-year period. MATERIALS AND METHODS: A total of 31
      consecutive patients with a mean age of 14 years (range 1 to 36) underwent
      laparoscopic assisted reconstructive surgery through a lower midline or
      Pfannenstiel incision by a single surgeon (SGD) between June 1995 and July 2002.
      Diagnoses included myelomeningocele (17), sacral agenesis (2), posterior urethral
      valves (2), classic bladder exstrophy (5), complicated ectopic ureter with
      ureterocele (1) and quadriplegia due to trauma (4). A total of 29 patients had 39
      continent stomas (antegrade continence enema [ACE] or Mitrofanoff) created as
      part of the reconstruction. One case was converted to an open procedure due to
      dense adhesions and was excluded from the study. Continent stoma construction
      included Mitrofanoff stomas created from appendix (17), ileum (3), sigmoid (5)
      and bladder (1), and ACE stomas from appendix (12) and ileum (1). Ten patients
      underwent concurrent Mitrofanoff and ACE procedures. Laparoscopy was used for
      lysis of adhesions, mobilization of colon and/or harvesting the appendix,
      nephrectomy in preparation for ureteral augmentation, division of pedicle for
      gastrocystoplasty takedown and harvesting of omentum for interposition. Bladder
      augmentation (15), bladder neck reconstruction (7), fascial sling (3), ureteral
      reimplants (1), revision of epispadias (2) and/or redo orchiopexy (1) were
      concurrently performed in 19 patients. Data were obtained through chart review
      and personal communication. RESULTS: Median hospital stay was 6 days (range 2 to
      20). Mean followup was 32 months (range 3 to 57). Revisions were required in 3
      stomas (7.7%) at a mean of 19 months (range 8 to 36) postoperatively. Minor
      procedures were required in 10 stomas (25.6%) consisting of indwelling
      catheterization, dilation, collagen injection and cystoscopy. Of the 39 stomas 37
      (94.9%) were continent of urine and/or stool, and easily catheterizable at last
      followup. Adequate capacity and compliance were maintained in all augmented
      bladders. No patient experienced delayed small bowel obstruction or other sequela
      of abdominal adhesions. CONCLUSIONS: At almost 3 years of mean followup
      laparoscopic assisted reconstructive surgery offers functional outcomes at least
      equivalent to conventional open surgery in complicated cases with excellent
      cosmesis. Laparoscopic assisted surgery remains our approach of choice for
      children and adults who require lower urinary tract reconstruction with a
      continent catheterizable stoma.

PMID- 14665935
TI  - Ureterocystoplasty: indications for a successful augmentation.
AB  - PURPOSE: We evaluate the outcome of ureterocystoplasty based on preoperative
      evaluations. MATERIALS AND METHODS: We reviewed preoperative ultrasound, voiding
      cystourethrography and preoperative/postoperative urodynamic studies (UDS) in 64
      patients undergoing ureterocystoplasty. RESULTS: Augmentation was performed with
      the distal 5 to 8 cm of a single megaureter in 8 patients without and 16 with
      grade 4 to 5/5 reflux. Median gain or loss in capacity and compliance was +0.14
      fold and -0.11-fold, respectively. Re-augmentation has occurred or is pending in
      23 cases (92%). Augmentation was performed in 40 patients with either a complete
      single or double collecting system. In 9 patients without reflux the diameter of
      the augmenting system was directly related to success. None of 6 with a ureteral
      diameter of greater than 1.5 cm required re-augmentation (median increase in
      bladder capacity and compliance 6 and 50-fold, respectively). Ureterocystoplasty
      was inadequate in 3 patients with a ureteral diameter of less than 1.5 cm and re
      augmentation was required. In 31 patients with reflux, preoperative UDS of the
      entire system was beneficial. If the system had either normal or mild
      noncompliance (greater than 20 ml/cm H2O) ureterocystoplasty improved compliance
      1-fold (6 cases) and re-augmentation not required. If UDS showed moderately or
      severely noncompliant system (less than 20 ml/cm H2O, 26 cases)
      ureterocystoplasty increased capacity and compliance by 0.4-fold (40%) and 0.25
      fold (25%), respectively. Re-augmentation has occurred or is pending in 21 of 26
      cases (81%). CONCLUSIONS: Ureterocystoplasty with any single or double collecting
      system is warranted in patients without reflux and a ureteral width greater than
      1.5 cm, and in patients with reflux and mild noncompliance (greater than 20 ml/cm
      H2O) on UDS.

PMID- 14665936
TI  - Intratesticular varicocele in adolescents: a reversible anechoic lesion of the
      testis.
AB  - PURPOSE: We describe ultrasonographic and clinical findings in adolescents with
      intratesticular varicocele. MATERIALS AND METHODS: Three adolescent boys 12 to 16
      years old each had a large intratesticular multicystic lesion on scrotal Doppler
      ultrasound for a large extratesticular varicocele. The presence of active Doppler
      flow within the anechoic lesions supported the diagnosis of intratesticular
      varicocele. RESULTS: All 3 boys underwent spermatic vein ligation for varicocele.
      In each case scrotal Doppler ultrasound at 3 months postoperatively demonstrated
      resolution of the intratesticular anechoic lesions and Doppler flow, confirming
      the diagnoses of intratesticular varicocele. CONCLUSIONS: Intratesticular
      varicocele is a clinically occult lesion that may occur in conjunction with
      extratesticular varicocele. This entity is apparent on scrotal Doppler ultrasound
      as an intratesticular anechoic lesion with active Doppler flow, and has been
      shown to resolve following spermatic vein ligation. Its clinical significance has
      not yet been defined.

PMID- 14665937
TI  - Fetoscopic placement of a transurethral stent for intrauterine obstructive
      uropathy.
AB  - PURPOSE: Fetal urinary obstructive uropathy and consecutive oligohydramnios
      result in a poor outcome. Usually renal insufficiency and life threatening lung
      hypoplasia have developed at term. We report a case of in utero fetal cystoscopy
      and successful placement of a transurethral vesico-amniotic Double-J (Medical
      Engineering Corp., New York, New York) stent. Indications, results and the
      potential benefits of different techniques are discussed. MATERIAL AND METHODS: A
      36-year-old woman (primipara) was evaluated at week 26 due to a male fetus with
      bilateral hydronephrosis, massive distended bladder and an open posterior
      urethra. Using local anesthesia the fetal bladder was punctured, a 2.6 mm
      endoscope was inserted and a wire was advanced antegrade through the penis. A
      2.8Fr Double-J stent was then placed between the bladder and amniotic cavity.
      RESULTS: The bladder drained into the amnion, hydronephrosis disappeared and the
      lung developed normally. At week 37 a healthy infant was delivered who voided
      spontaneously. CONCLUSIONS: After careful selection of candidates for fetal
      intervention in obstructive uropathy direct vision fetoscopy and transurethral
      stent placement can be performed in patients with oligohydramnios, favorable
      urinary electrolytes and normal appearing kidneys.

PMID- 14665938
TI  - Isolated renal mucormycosis in children.

PMID- 14665939
TI  - Pediatric tuberculous vesicovaginal fistula.

PMID- 14665940
TI  - Acute epididymitis in boys: evidence of a post-infectious etiology.
AB  - PURPOSE: We studied the etiology and management of pediatric epididymitis.
      MATERIAL AND METHODS: We performed 1-year prospective study in children with
      epididymitis. All patients underwent an immediate sonographic study of the
      scrotum. Microbiological studies included throat and urine cultures as well as
      viral cultures of nasopharyngeal and stool specimens. Serological tests for group
      A streptococcus and Mycoplasma pneumoniae as well as for enteroviruses,
      adenoviruses, influenza and parainfluenza viruses in the appropriate seasons were
      performed in patients and controls. RESULTS: A total of 44 patients 2 to 14 years
      old (mean age 9.8 +/- 3.2) were studied. Hospital admissions peaked during the
      summer and winter. The incidence of epididymitis was around 1.2/1,000 boys
      yearly. One patient had familial Mediterranean fever and another had Henoch
      Schonlein purpura. Microbiological studies of the urine, throat, nasopharynx and
      stool yielded bacterial/viral growth in 9 patients (20.4%). Serological studies
      revealed significantly elevated titers to certain pathogens in patients with
      epididymitis compared with controls, including M. pneumoniae (53% vs 20%),
      enteroviruses (62.5% vs 10%) and adenoviruses (20% vs 0%). Most patients were
      treated with analgesics and 3 patients received antibiotics intravenously.
      Systemic and local signs and symptoms resolved gradually in 1 to 7 days.
      CONCLUSIONS: Our results suggest that epididymitis in boys is not rare and it is
      mostly an inflammatory phenomenon (presumably post-infectious) with a benign
      course. The treatment of these patients is basically with analgesics with a
      little role for antibiotics.

PMID- 14665941
TI  - Obstruction of a dysmorphic ureter following dextranomer/hyaluronic acid
      copolymer.

PMID- 14665942
TI  - Factors associated with the outcomes of children with unilateral ureteropelvic
      junction obstruction.
AB  - PURPOSE: Children with congenital unilateral ureteropelvic junction obstruction
      were evaluated with 99mtechnetium-labeled diethylenetriaminepentaacetic acid
      furosemide renal scans (DTPA) to determine the correlation of tubular function
      tests, growth factors and renal function. MATERIALS AND METHODS: A total of 38
      children diagnosed with congenital unilateral ureteropelvic junction obstruction
      and recipients of dismembered pyeloplasty were prospectively studied. Before
      pyeloplasty split renal tubular function, creatinine clearance, urinary growth
      factors and a marker for apoptosis of each kidney were examined. Renal function
      of the obstructed kidney was evaluated by DTPA before and after pyeloplasty.
      Initially patients with DTPA greater than 40% were designated group 1 and those
      with DTPA 40% or less were assigned to group 2. After surgery followup patients
      with DTPA greater than 40% were designated the well preserved group and those
      with DTPA 40% or less were assigned to the poorly preserved group. Statistical
      analyses were performed to determine the best predictive variable for treatment.
      RESULTS: Mean initial DTPA split renal function values of groups 1 and 2 were
      47.3% and 28.8%, respectively and subsequently, they were 48.4% and 35.3%.
      Initial DTPA on the obstructed side of less than 35% had a 100% sensitivity and
      100% positive predictive rate for a poorly preserved renal outcome. Among the
      various tubular functions, only percent fractional excretion of sodium and
      percent fractional excretion of chloride correlated with post-pyeloplasty DTPA.
      Urinary epidermal growth factor/creatinine correlated with preservation of renal
      function on postoperative DTPA renal scans. Although urinary transforming growth
      factor/creatinine levels and apoptosis ratios were higher on the obstructed side,
      they were not significantly different between the groups. CONCLUSIONS: Proximal
      tubular dysfunction, such as increased percent fractional excretion of sodium and
      chloride, and initial DTPA 35% or less, suggest a high possibility of poorly
      preserved renal outcome. Urinary transforming growth factor-beta1 and apoptosis
      are not correlated with renal outcome. A high urinary level of epidermal growth
      factor might be a potential indicator of preservation of renal growth.

PMID- 14665943
TI  - The micturition habits and prevalence of daytime urinary incontinence in Japanese
      primary school children.
AB  - PURPOSE: We assessed the prevalence of daytime urinary incontinence (DUI) and the
      daytime frequency of voiding by age and sex in neurologically normal children in
      primary school. We also investigated the association of DUI with background
      factors. MATERIALS AND METHODS: We performed an anonymous questionnaire survey of
      DUI in primary school children. A total of 11 primary schools in Hiroshima City
      were randomly selected and 6,917 school children 7 to 12 years old were enrolled.
      DUI was defined as any involuntary leakage of urine during the daytime occurring
      more frequently than once monthly in the 6 months before the survey. Slight
      dampness of the child underwear was also regarded as DUI. RESULTS: The overall
      response rate was 76.4% of 6,917 school children. The prevalence of DUI was 6.3%
      and it was inversely related to age, decreasing from about 9% at age 7 to 2% at
      age 12 years. Children urinated about 5 or 6 times daily and increased daytime
      frequency occurred in 14.6% of all children. Daytime frequency of voids, history
      of cystitis and infrequent bowel habits had a statistically significant positive
      correlation with DUI. CONCLUSIONS: We found that the overall prevalence of DUI in
      primary school children was 6.3%, gradually decreasing with age. Increased
      daytime frequency, history of cystitis and infrequent bowel habits were
      significantly related to DUI. The link between DUI and daytime frequency, urinary
      tract infections and constipation deserves more attention.

PMID- 14665944
TI  - Behavioral therapy for primary nocturnal enuresis.
AB  - PURPOSE: Recent studies suggest the efficacy of behavioral therapy for enuresis,
      even in cases of minor daytime voiding problems. We describe our experience with
      the clinical followup and behavioral therapy of children with primary enuresis.
      MATERIALS AND METHODS: We followed 159 boys and 91 girls 5 to 17 years old with
      primary enuresis who were treated at 3 medical centers with a pediatric
      nephrology clinic during the last 3 years. A detailed voiding history was
      obtained. Each child was treated with a bladder training session, including an
      explanation of the enuretic process, daily diary recording and training to
      recognize bladder distention and increase voiding frequency. RESULTS: A total of
      226 children (90%) presented with 1 or more symptoms of bladder maturation delay
      and 13% reported behavioral constipation. Of the patients 185 (74%) completed the
      proposed treatment, including 111 (60%) who reported a positive and 21 (11%) who
      reported a partial response. In 53 children (29%) the treatment failed.
      CONCLUSIONS: Most children with enuresis have daytime symptoms when an accurate
      history is recorded. As shown by our data, the efficacy of behavioral therapy is
      comparable to that of desmopressin or alarm therapy but it requires good
      compliance of the child with the therapeutic plan. Age is not a determining
      factor in the success rate.

PMID- 14665945
TI  - The adolescent varicocele: diagnostic and treatment patterns of pediatricians. A
      public health concern?
AB  - PURPOSE: We determine whether practice patterns of pediatricians contribute to
      delays in diagnosing and treating adolescents with varicoceles. MATERIALS AND
      METHODS: A survey consisting of 11 multiple-choice questions was mailed to 5,000
      pediatricians selected by zip code in New York State. Zip codes were chosen to
      reflect urban, suburban and rural counties. RESULTS: A total of 544 of the 5000
      (10.9%) surveys were returned, and 92 (16.9%) pediatricians acknowledged that
      they did not routinely perform physical examinations of the genitalia of
      adolescent males patients. Of 497 pediatricians who routinely or occasionally
      examine the genitalia 54 (10.9%) did not examine for the presence of varicoceles.
      When pediatricians were asked how they assess for the presence of varicoceles, 13
      of 521 (2.5%) only used visual inspection, 50 (9.6%) only examined patients in
      the supine position and 379 (72.7%) of these pediatricians never used Valsalva
      maneuvers. Of 517 respondents 442 (85.5%) referred patients with varicoceles to a
      urologist for followup and 72 (13.9%) did no further evaluation. When asked to
      indicate what they thought was the greatest concern regarding the pediatric
      varicocele, 327 of 497 (65.0%) pediatricians indicated deterioration of future
      infertility, 120 (30.0%) indicated testicular growth retardation, 105 (24.2%)
      indicated pain and 18 (4.3%) indicated cosmesis. CONCLUSIONS: A significant
      percentage of pediatricians do not routinely perform physical examinations for
      varicoceles or appropriately examine for varicoceles, despite the majority being
      aware of the potential significance of varicoceles. This study demonstrates the
      need for increased educational efforts among pediatricians regarding the need for
      physical examination of the genitalia, the techniques for appropriate physical
      examination, and the need for appropriate referral and followup of adolescents
      with varicoceles.

PMID- 14665946
TI  - Oligoclonality in bladder cancer: the implication for molecular therapies.
AB  - PURPOSE: There is conflicting evidence in the published literature regarding the
      clonal or oligoclonal origin of bladder cancer. MATERIALS AND METHODS: A MEDLINE
      search of articles on the clonality, genetic, epigenetic and tumor
      microenvironment of bladder cancer cells was done. Laboratory and clinical
      studies were included and relevant articles were selected if tumor cell clonality
      was part of the study. We reviewed this published evidence. RESULTS: Current
      thinking proposes 2 main theories. 1) In the clonogenic theory multifocal and
      recurrent tumors evolve from a single transformed cell and, hence, all progeny
      share a number of identical genetic mutations. 2) The field change theory assumes
      a global change in the urothelium with multiple transformed cells evolving into
      mature tumors independently. The evidence for and against each theory is
      compelling. Of equal importance are the parallel epigenetic modifications and
      changes in the cellular microenvironment that permit tumor evolution.
      CONCLUSIONS: The presence of oligoclonality has implications for the potential
      efficacy of novel molecular therapeutic agents for bladder cancer. The molecular
      targets for such therapies must be widely sampled in a tumor population to assess
      expression in separate clones.

PMID- 14665947
TI  - Over expression of CD44V8-10 in human bladder cancer cells decreases their
      interaction with hyaluronic acid and potentiates their malignant progression.
AB  - PURPOSE: We evaluated the effects of the over expression of CD44v8-10, one of the
      high molecular form of CD44, on the malignant potential of UM-UC-3 human bladder
      cancer cells in vitro and in vivo. MATERIALS AND METHODS: We introduced CD44v8-10
      complementary DNA into UM-UC-3 cells, which do not express detectable level of
      CD44v8-10 protein, and generated the CD44v8-10 over expressing cell line UM-UC
      3/v8-10 and the vector only transfected cell line UM-UC-3/C. The effects of the
      introduction of CD44v8-10 into UM-UC-3 cells on the ability to bind hyaluronic
      acid (HA) were analyzed by the cell adhesion assay and the cell migration assay.
      We then evaluated tumor progression of UM-UC-3 sublines after subcutaneous and
      orthotopic injection into athymic nude mice. RESULTS: There were no significant
      differences in in vitro growth rates. UM-UC-3/v8-10 cells showed significantly
      decreased binding and migration ability to HA but not to other extracellular
      matrix proteins. Furthermore, UM-UC-3/v8-10 cells demonstrated significantly
      increased tumor growth after subcutaneous as well as orthotopic injection into
      athymic nude mice and enhanced lymph node metastasis after orthotopic injection
      compared with UM-UC-3/C cells. CONCLUSIONS: These findings suggest that CD44v8-10
      over expression in human bladder cancer cells decreases their interaction with HA
      and potentiates their malignant progression.

PMID- 14665948
TI  - Germline mutation analysis of the androgen receptor gene in Finnish patients with
      prostate cancer.
AB  - PURPOSE: Steroid hormones, particularly androgens, are suspected to have a major
      role in prostate carcinogenesis. Since androgen receptor mediates androgenic
      effects on cells and recent studies suggest that the androgen receptor gene is a
      putative prostate cancer susceptibility locus, we screened the coding region of
      the androgen receptor gene for germline mutations using the genomic DNA of
      patients with prostate cancer. MATERIALS AND METHODS: DNA samples from 38
      patients with early onset prostate cancer and 36 from Finnish prostate cancer
      families showing no male-to-male transmission of prostate cancer were analyzed
      for mutations in the androgen receptor gene using single strand conformation
      polymorphism analysis and subsequent sequencing. RESULTS: R726L substitution in
      the hormone binding region of androgen receptor was found in 1 prostate cancer
      family but no previously uncharacterized germline mutations were detected.
      CONCLUSIONS: Our results indicate that constitutional androgen receptor mutations
      explain only a small fraction of familial and early onset prostate cancer cases
      in Finland.

PMID- 14665949
TI  - Pigment epithelium-derived factor, a human testis epididymis secretory product,
      promotes human prostate stromal cell growth in culture.
AB  - PURPOSE: We identified and characterized unrecognized testicular secretory
      proteins that impact human prostate growth. MATERIALS AND METHODS: Human
      spermatocele fluid served as a source of testicular epididymal secretions and
      prostatectomy specimen benign prostatic hyperplasia stromal cells as the in vitro
      prostate growth promoting effects indicator. RMPI plus medium supplemented with
      10% fetal bovine serum MALDI-TOF, MS FBS and ITS+ (Collaborative Research-Becton
      Dickinson, Bedford, Massachusetts) served as positive and negative controls,
      respectively. Whole and fractionated spermatocele fluid or specific proteins
      without and with select polyclonal or monoclonal antibodies were added to routine
      6-day cultures. The observation of significantly increased 6-day cell counts
      compared with appropriate controls (p <0.05) was judged to reflect cell growth.
      Amino acid microsequencing and MALDI-TOF MS sequence analysis were done on
      persistent protein bands from active spermatocele fluid fractions. RESULTS: Whole
      and fractionated human spermatocele fluid increased stromal cell culture numbers
      significantly. Sequence analysis of 47 and 17 kDa 1-dimensional gel bands in the
      final active fraction identified a major peptide with sequence homology to human
      pigment epithelium-derived factor (PEDF). The presence of PEDF was confirmed by
      Western blot analysis. Addition of recombinant PEDF to incomplete medium
      significantly increased stromal cell culture number. PEDF antibodies neutralized
      or markedly decreased the stromal stimulating effect of spermatocele fluid and
      PEDF. CONCLUSIONS: The observations presented provide evidence for human
      testis/epididymis secretion of PEDF and for a PEDF in vitro growth promoting
      effect on benign prostatic hyperplasia stroma. The concept that testicular
      epididymal secretory proteins may influence normal and abnormal prostate growth
      warrants continued consideration.

PMID- 14665950
TI  - An allograft model of androgen independent prostatic neuroendocrine carcinoma
      derived from a large probasin promoter-T antigen transgenic mouse line.
AB  - PURPOSE: Animal models that mimic this hormone refractory prostate cancer may be
      useful for developing and testing novel treatment strategies. MATERIALS AND
      METHODS: Using the prostate of the 12T-10 transgenic mouse an allograft model was
      established by transplantation into a nude mouse. To our knowledge we describe
      the first allograft model derived from the primary prostate tumor of a transgenic
      mouse. RESULTS: The primary tumor progressed from high grade prostatic
      intraepithelial neoplasm to invasive, undifferentiated and metastatic cancer with
      loss of androgen receptor expression. After 10 passages in nude mice the
      allograft retained the same histological and immunohistochemical features as the
      primary tumors, including neuroendocrine differentiation. The allograft
      demonstrated androgen independent growth and metastases to liver and lung,
      paralleling tumor behavior in the original transgenic line. Cytogenetic
      characterization of the allograft revealed consistent chromosomal abnormalities
      for multiple in vivo passages. CONCLUSIONS: This allograft model may give insight
      into the mechanism by which human prostate cancer progresses to an androgen
      independent state and provide a system for testing drugs that can inhibit this
      disease.

PMID- 14665951
TI  - Why we must better understand neuroendocrine differentiation in prostate cancer.

PMID- 14665952
TI  - Central renal stab wounds: treatment with augmented fibrin sealant in a porcine
      model.
AB  - PURPOSE: We determined whether fibrin sealant augmented by an absorbable bolster
      could salvage kidneys with major, centrally located stab wounds. MATERIALS AND
      METHODS: A grade 4 renal injury was created in 16 commercial swine via a 1.5 cm
      sagittal, centrally located, through-and-through right renal laceration. Animals
      were randomized to 1 of 4 treatment arms, including control groups that received
      conventional renal capsule suture repair with an absorbable gelatin sponge
      bolster (3 in group 1) or a microfibrillar collagen sheet (3 in group 2) and
      experimental groups that received sutureless treatment entailing fibrin sealant
      instillation into the knife tract augmented by an external gelatin sponge (5 in
      group 3) or an external microfibrillar collagen sheet (5 in group 4). Arterial
      occlusion was not performed. Blood loss and time to hemostasis were recorded.
      Abdominal computerized tomography was performed at 1 week and necropsy was done
      at 6 weeks. RESULTS: Renal reconstruction with fibrin sealant resulted in
      significantly lower blood loss (62 vs 155 ml, p <0.05) and time to hemostasis
      (3.5 vs 6.5 minutes, p <0.05) than in the conventional suture groups. There was
      no radiographic or gross evidence of significant postoperative bleeding, urinoma
      formation or abnormal tissue healing in the recovery period. Gelatin sponge and
      collagen sheet demonstrated similar hemostatic efficacy. CONCLUSIONS: In this
      porcine renal trauma model fibrin sealant augmented by absorbable gelatin sponge
      or a microfibrillar collagen sheet effectively promoted hemostasis and renal
      salvage. Because of its safety, ease of use and efficiency, fibrin sealant
      appears to be an appropriate adjunct for managing challenging renal injuries.

PMID- 14665953
TI  - Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from
      patients with interstitial cystitis.
AB  - PURPOSE: Extracellular adenosine triphosphate (ATP) can act through the
      purinergic receptor subtype P2X3 to transmit a pain signal to the central nervous
      system. Bladder urothelial cells (BUCs) from patients with interstitial cystitis
      (IC) patients have augmented release of ATP during in vitro stretch. We queried
      whether P2X3 receptor subtype exists on cultured BUCs. Furthermore, we asked
      whether P2X3 expression can be altered by in vitro stretch and whether there
      exists a difference in expression between IC and control BUCs. MATERIALS AND
      METHODS: BUCs from 4 IC and 5 control subjects were cultured according to
      established cell culture techniques. After cells were grown to confluence they
      were stretched on an in vitro stretch machine at 20% elongation for up to 96
      hours. Cells were harvested at various times, and immunofluorescence and Western
      blots were performed for P2X3 expression. Band densitometry normalized to the
      actin band was performed using software. To confirm P2X3 expression in a whole
      cell preparation flow cytometry and fluorescence activated cell sorter analysis
      were used. RESULTS: P2X3 was expressed in cultured BUCs. With stretch P2X3
      expression increased in IC BUCs more than in control BUCs. Using relative
      densitometry units normalized for actin expression in the Western blots stretch
      of IC BUCs resulted in 66% more expression of P2X3 than any other experimental
      condition (p = 0.003). By fluorescence activated cell sorter analysis stretched
      IC BUCs had the highest P2X3 fluorescence activity (30%) compared with
      unstretched IC (2.4%, p = 0.003), stretched control (9.7%, p = 0.009) and
      unstretched control (2.3%, p = 0.003) BUCs. CONCLUSIONS: These data show that
      P2X3 subunits expressed by cultured IC BUCs are up-regulated during in vitro
      stretch. Augmented ATP signaling in the bladder may explain IC symptoms.
      Furthermore, this study further supports the hypothesis that urothelial cells can
      phenotypically mimic sensory neurons.

PMID- 14665954
TI  - Acellular matrix tube for canine urethral replacement: is it fact or fiction?
AB  - PURPOSE: We evaluated the results of acellular matrix used as a tube for
      replacement of a relatively long segment of the canine urethra. MATERIALS AND
      METHODS: The study included 9 female and 5 male mongrel dogs in which a 3 cm
      segment of the whole urethral circumference was excised and replaced by a tube of
      acellular matrix of the same length and width. The acellular matrix was obtained
      by excision of the whole urethra of donor female dogs that were sacrificed and
      not included in the study group. The retrieved urethra was treated to have
      complete cell lysis with maintenance of the fiber framework. In all dogs the
      urethra was stented for 4 weeks. Ascending urethrogram was done after stent
      removal every month until the dogs were sacrificed. The dogs were sacrificed at a
      rate of 1 weekly for 4 weeks and then monthly. If urine retention occurred,
      ascending urethrogram was performed and the dog was sacrificed. Before sacrifice
      the urethra was exposed and carefully examined. The whole specimen was then
      excised for histopathological examination. RESULTS: All dogs survived surgery and
      no postoperative complications were seen during urethral stenting. After stent
      removal all dogs had a urethral fistula and/or stricture, which increased in
      severity until urine retention occurred by the end of month 3. Exploration at 1,
      2, 3 and 4 weeks showed an intact graft, although there was progressive shrinkage
      in length and urethral calibration also demonstrated progressive narrowing of the
      lumen. At 3 months there was marked shrinkage (length equaled 0.3 cm) and
      complete obliteration of the lumen. Histopathological examination showed
      progressive fibrosis, which was extensive by week 4. CONCLUSIONS: Acellular
      matrix tube is not able to replace a 3 cm segment of canine urethra.

PMID- 14665955
TI  - Mechanical deformation induced apoptosis in human proximal renal tubular
      epithelial cells is caspase dependent.
AB  - PURPOSE: Ureteral obstruction (UO) results in apoptosis of renal tubular
      epithelial cells. We postulated that mechanical deformation and inflammation
      contribute to the cellular loss that occurs as a result of UO and it is mediated
      through altered heat shock protein 70 (HSP-70) expression and the caspase
      cascade. MATERIALS AND METHODS: Human HK-2 renal tubular cells were subjected to
      mechanical stretch. Cell viability and apoptosis were assessed by flow cytometry;
      HSP-70 and caspase 3 protein expression by Western blotting, and caspase 3
      activity by fluorescence substrates. RESULTS: Mechanical stretch caused direct
      apoptosis induction and it also primed for tumor necrosis factor-alpha induced
      apoptosis, which was caspase 3 dependent. Although HSP-70 protein expression was
      increased during mechanical stretch, the protective effects of HSP-70 were only
      seen after further induction by heat shocking. CONCLUSIONS: Altering HSP-70
      expression and manipulating the caspase cell death proteases represent a novel
      pathway to protect against renal tubular cell apoptosis and the potential for
      progression to renal failure in UO.

PMID- 14665956
TI  - Monocyte chemoattractant protein-1 production by human detrusor smooth muscle
      cells.
AB  - PURPOSE: Most recently attention has turned to the secretory properties of smooth
      muscle cells. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine
      that causes mast cells recruitment and provokes mast cells activation in vitro.
      We investigated whether MCP-1 is produced by human detrusor smooth muscle cells
      (HDSMCs) cultured under inflammatory conditions. MATERIALS AND METHODS: Using an
      explantation technique HDSMCs were isolated and short-term cultured. HDSMCs were
      incubated at 37C for 24 hours with the proinflammatory mediators interleukin-1
      beta (IL-1 beta), tumor necrosis factor (TNF-alpha), lipopolysaccharide,
      histamine, leukotriene D4 and prostaglandin E2. The level of MCP-1 in cell
      supernatants were measured by enzyme linked immunoassay. RESULTS: There was basal
      secretion of MCP-1 in unstimulated cultures. Following 24-hour incubation with IL
      1 beta or TNF-alpha (1 pg/ml to 100 ng/ml) the level of MCP-1 increased in a dose
      dependent manner. IL-1 beta was more potent at inducing MCP-1 release in 8 of 10
      experiments. Lipopolysaccharide (10 microg/ml), histamine (100 microM),
      leukotriene D4 (50 nM), prostaglandin E2 (1 microM) and KCl (30 to 100 mM) failed
      to induce MCP-1 production. When IL-1 beta (10 ng/ml) and TNF-alpha (10 ng/ml)
      were given in combination, a highly synergistic effect on MCP-1 production was
      observed. CONCLUSIONS: To our knowledge this study shows for the first time that
      human detrusor smooth muscle cells cultivated under inflammatory conditions
      produce significant amounts of MCP-1. In addition to contractile function, HDSMCs
      have synthesis and secretory potential with the release of MCP-1. Thus, MCP-1 may
      contribute to the local inflammatory process by producing proinflammatory
      mediators. The release of cytokines and chemokines by human detrusor muscle even
      in small amounts may have important functional consequences.

PMID- 14665957
TI  - Estrogen and postnatal maturation increase caveolar number and caveolin-1 protein
      in bladder smooth muscle cells.
AB  - PURPOSE: Clinical studies indicate that detrusor contractility decreases in old
      age and the dense band pattern with caveolar depletion represents the
      ultrastructural norm of the aged human detrusor. We performed animal studies to
      explore the hypothesis that lowering estrogen induces the dense band pattern with
      estrogen replacement restoring usual sarcolemmal appearance and increasing
      caveolar number. MATERIALS AND METHODS: Newborn, young (1-month-old) and middle
      aged (13 to 14-month-old) female rats were studied. Middle-aged animals were
      evaluated 4 months after sham operation or ovariectomy (OVx) with OVx rats
      receiving placebo or 25% 17beta-estradiol (E2) capsules for 1 week prior to
      sacrifice. Electron microscopy was used to evaluate sarcolemmal structure and
      quantify caveolar numbers in bladder muscle cells. Caveolae were also assessed by
      measuring caveolin-1 protein. RESULTS: Alternating electron dense and thinner
      zones with abundant caveolae were present in bladder sarcolemma from middle-aged
      animals. Newborn and OVx sarcolemma showed many ultrastructural features of the
      dense band pattern with fewer caveolae present per micro sarcolemma or per muscle
      cell compared with sham operated middle-aged controls. E2 replacement decreased
      the dense band pattern and increased caveolar numbers in OVx animals. Caveolin-1
      protein levels underwent similar changes following maturation, OVx and E2
      replacement, while alpha-smooth muscle actin remained unchanged. CONCLUSIONS:
      Prolonged estrogen withdrawal results in sarcolemmal changes in middle-aged
      animals, similar to the dense pattern observed in newborns. Estrogen replacement
      decreases the dense pattern, while increasing caveolar numbers and caveolin-1
      protein. It remains to be seen whether estrogen influences caveolar depletion
      and/or contractility in human bladders.

PMID- 14665958
TI  - Induction of bladder sphincter dyssynergia by kappa-2 opioid receptor agonists in
      the female rat.
AB  - PURPOSE: The nonselective kappa opioid receptor agonist ethylketocyclazocine
      suppresses external urethral sphincter (EUS) reflexes in cats. We examined the
      role of spinal kappa-opioid receptor subtypes in the control of EUS function in
      rats using selective kappa-1 (U-50,488) or kappa-2 (GR-89,696) opiate receptor
      agonists. MATERIALS AND METHODS: Urethane anesthetized female rats were
      catheterized through the bladder dome for cystometry. EUS function was assessed
      electromyographically. Drugs were administered intrathecally or intravenously.
      RESULTS: Micturition in rats is accompanied at different times by tonic
      (continuous) EUS spike activity and by phasic bursts of spikes separated by
      pauses. GR-89,696 (0.05 to 5 microg intrathecally) caused a dose dependent
      decrease in the number of bursts per micturition without affecting spike
      frequency within individual bursts or during periods of tonic activity. It
      resulted in decreased voiding efficiency and at high doses dyssynergia and
      overflow incontinence. The nonselective opiate receptor antagonist naloxone (1
      mg/kg intravenously) blocked GR-89,696 effects. U-50,488H (0.05 to 15 microg
      intrathecally) caused no change in cystometric parameters or in EUS
      electromyography. CONCLUSIONS: Efficient voiding in rats depends on a spinal
      pattern generator causing EUS motor neuron firing to occur in bursts, resulting
      in rapid urethral contraction and relaxation. Intrathecal kappa-2-opiate receptor
      agonists suppress this pattern generator, decreasing the number of bursts
      occurring during each micturition without decreasing motor neuron spike frequency
      during individual bursts or during tonic spike activity associated with urethral
      closure. Resultant dyssynergia leads to decreased voiding efficiency. The
      relevance of kappa-2 opioid receptors should be explored in higher species,
      especially regarding spinal cord injury induced dyssynergia.

PMID- 14665959
TI  - Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve
      growth factor in lumbosacral spinal cord in spinal cord injured rats.
AB  - PURPOSE: We investigated the effects of intrathecal application of nerve growth
      factor (NGF) antibodies (NGF-Abs) and desensitization of C-fiber afferent
      pathways by capsaicin treatment on detrusor-sphincter dyssynergia (DSD) after
      spinal cord injury (SCI). MATERIALS AND METHODS: In adult female rats SCI was
      induced by complete transection of the spinal cord at Th8 to 9. Ten days after
      spinalization vehicle or NGF-Ab (10 microg daily) was continuously administered
      at the level of the L6-S1 spinal cord through an implanted intrathecal catheter
      connected to an osmotic pump for 2 weeks. Another group of spinalized rats was
      treated with capsaicin (125 mg/kg subcutaneously) 3 weeks after spinalization and
      5 days before experiments. Simultaneous recordings of intravesical pressure and
      urethral perfusion pressure were then performed. NGF levels in the L6 spinal cord
      were measured in vehicle or NGF-Ab treated spinalized rats using enzyme-linked
      immunosorbent assay. RESULTS: DSD was observed in all vehicle treated spinalized
      rats. The average urethral pressure increase at the peak bladder contraction was
      significantly lower by 84% and 78% in NGF-Ab and capsaicin treated spinalized
      rats, respectively, than in vehicle treated rats. After NGF-Ab treatment NGF
      levels were significantly decreased by 38% in the L6 spinal cord compared with
      vehicle treated spinalized rats, in which NGF levels in the L6 spinal cord were 7
      times higher than in spinal intact rats. CONCLUSIONS: Increased levels of NGF in
      the spinal cord could contribute to the emergence of DSD that is at least in part
      mediated by C-fiber bladder afferents after SCI. Thus suppression of NGF levels
      in afferent pathways could be useful for treating DSD following SCI.

PMID- 14665960
TI  - Urodynamic and immunohistochemical evaluation of intravesical capsaicin delivery
      using thermosensitive hydrogel and liposomes.
AB  - PURPOSE: Aqueous insolubility of the vanilloids such as capsaicin is a major
      disincentive in their intravesical therapy of detrusor hyperreflexia. We sought
      to overcome the delivery of this hydrophobic neurotoxin by entrapping it in a
      lipid bilayer of positively charged multilamellar lipid vesicles (liposomes) or
      in a hydrophobic polymer matrix of thermosensitive hydrogel. MATERIALS AND
      METHODS: Liposomes, hydrogel and 30% ethanol/normal saline were prepared with or
      without 1 mM capsaicin (0.5 ml) and administered intravesically for 30 minutes to
      7 groups of age matched, normal female adult Sprague-Dawley rats under halothane
      anesthesia. At 48 hours after intravesical instillation cystometric studies were
      performed using urethane anesthesia (0.04 ml per minute). The animals were
      subsequently sacrificed and whole bladders were harvested for histology and
      immunohistochemistry. RESULTS: In normal urethane anaesthetized rats capsaicin in
      30% ethanol and liposomes completely blocked micturition reflexes. Capsaicin in
      hydrogel did not completely block the micturition reflex but it significantly
      decreased bladder contraction frequency compared with vehicle controls. The
      results of cystometry with capsaicin in liposomes and capsaicin in 30% ethanol
      correlated with a significant decrease in calcitonin gene-related peptide
      staining of afferent nerves in the bladder wall. Photographs taken after
      hematoxylin and eosin staining of the bladder treated with liposomes and hydrogel
      in the absence of capsaicin did not reveal any adverse histological changes.
      There were significant histological changes in bladders treated with 30% ethanol
      alone. CONCLUSIONS: In comparison with 30% ethanol liposomes are a superior
      vehicle for the intravesical administration of capsaicin, producing comparable
      efficacy with less tissue damage. Hydrogel can also serve as safe alternative
      option for capsaicin delivery.

PMID- 14665961
TI  - Modulation of intrinsic cavernous tone and nitric oxide production by arginase in
      rabbit corpus cavernosum.
AB  - PURPOSE: Arginase shares the common substrate L-arginine with nitric oxide
      synthase (NOS). We investigated the roles of NOS and arginase for modulating
      intrinsic and vasoconstrictor tone in rabbit corpus cavernosum (RCC). MATERIALS
      AND METHODS: Isolated RCC tissues were used for isometric tension experiments,
      and NOS and arginase activities. The endothelium lining RCC lacunar spaces was
      disrupted and/or removed by saponin treatment. RESULTS: Following stretch of
      approximately 1gm NG-nitro-L-arginine methyl ester (L-NAME) as a NOS inhibitor
      caused endothelium dependent contraction, while the potent and specific arginase
      inhibitor N omega-hydroxy-nor-L-arginine (nor-NOHA) caused endothelium dependent
      relaxation. Relaxation with nor-NOHA was reversed by L-NAME. In the presence of
      10 mM L-arginine 0.1 mM nor-NOHA was ineffective. Pretreatment with 0.1 mM L-NAME
      and 0.1 mM nor-NOHA did not significantly affect the vasoconstrictor response to
      phenylephrine. The magnitude of contraction with 0.1 mM L-NAME and relaxation
      with 0.1 mM nor-NOHA during contraction induced by phenylephrine were not
      significantly different from changes with L-NAME and nor-NOHA under intrinsic
      basal tone. In the enzymatic study NOS and arginase were detectable in cavernous
      homogenates. Nor-NOHA inhibited arginase but not NOS activity. CONCLUSIONS:
      Results indicate that basal nitric oxide production from the endothelium
      regulates intrinsic cavernous tone and endogenous arginase activity in the
      endothelium modulates tone by inhibiting nitric oxide production, presumably
      through competition with constitutive NOS for the common substrate L-arginine.

PMID- 14665962
TI  - Immunophilin ligands promote penile neurogenesis and erection recovery after
      cavernous nerve injury.
AB  - PURPOSE: We investigated the long-term effect of immunophilin ligands on erection
      physiology and cavernous tissue histology using rat models of unilateral and
      bilateral cavernous nerve (CN) injury. MATERIALS AND METHODS: Adult male Sprague
      Dawley rats were administered the immunophilin ligand FK506 (5 mg/kg
      subcutaneously daily for 5 days), the nonimmunosuppressant FK506 derivative
      GPI1046 (3 to 3-pyridyl)-1-propyl(2 seconds)-1-(3,3-dimethyl-1,2-dioxopentyl)-2
      pyrrolidine carboxylate) (40 mg/kg subcutaneously daily for 5 or 28 days) or
      saline immediately upon induction of 2 paradigms of cavernous nerve injury,
      namely focal transection of the CN unilaterally, and a combination of focal
      transection of the CN unilaterally and excision of a 5 mm segment of
      contralateral CN (BIL treated). At 28 days following CN injury electrical
      stimulation of the transected CN and penile erection monitoring were performed.
      Whole penes were removed and evaluated immunohistochemically for the nitric oxide
      generator neuronal nitric oxide synthase, the neuronal marker synaptophysin, the
      endothelial marker CD31 and the smooth muscle marker alpha-actin. RESULTS: In
      unilaterally treated groups erection recovery was significantly greater in FK506
      treated than in saline treated animals ((83.5% +/- 9.2% vs 24.3% +/- 8.1%, p
      <0.001) and similarly greater in GPI1046 treated animals than in the respective
      saline treated controls for this group (57.9% +/- 12.6% vs 23.8% +/- 7.0%, p
      <0.05). In BIL treated groups erection recovery for FK506 and GPI1046 treated
      rats exceeded saline treated values by approximately 70% (p <0.05) and 40% (p =
      0.14), respectively. After 28 days of continuous treatment in BIL treated groups
      erection recovery for GPI1046 treated rats exceeded saline treated values by 140%
      (p <0.05). Neuronal and endothelial staining was preserved after immunophilin
      ligand treatment. CONCLUSIONS: Immunophilin ligands exert neurotrophic effects on
      the penile innervation that preserve cavernous tissue structure and promote
      erectile function recovery in rats after extensive CN injury.

PMID- 14665963
TI  - Experimental varicocele induces testicular germ cell apoptosis in the rat.
AB  - PURPOSE: We evaluated the impact of experimentally created varicocele on
      ipsilateral and contralateral testicular germ cells in the rat. MATERIALS AND
      METHODS: Experimental left varicocele was created by partial ligation of the left
      renal vein in 17 adult male Sprague-Dawley rats. An additional 5 rats that
      underwent laparotomy and renal vein handling without ligation served as sham
      surgical controls. Five rats that underwent no surgical or other intervention
      served as a control group. Rats were sacrificed 7 (5), 14 (5) or 28 (7) days
      following varicocele creation. Germ cell apoptosis was quantified using a TUNEL
      assay. The results of this assay are expressed as the number of apoptotic germ
      cell nuclei per seminiferous tubular cross section. The presence of apoptosis was
      confirmed by cellular ultrastucture evaluation using transmission electron
      microscopy. RESULTS: Control and sham animals were found to have a mean of 0.05
      and 0.15 apoptotic germ cells per seminiferous tubular cross section,
      respectively. Rats sacrificed 7, 14 and 28 days after varicocele creation were
      found to have 0.15, 0.23 and 0.27 apoptotic germ cells per tubule in the
      ipsilateral testis, and 0.14, 0.16 and 0.17 apoptotic germ cells per tubule in
      the contralateral testis, respectively. Compared with control animals a
      statistically significant increase in the number of apoptotic germ cells per
      tubular cross section was noted 14 days following varicocele creation in the
      ipsilateral testis (p <0.05). CONCLUSIONS: The creation of experimental
      varicocele generated an increase in germ cell apoptosis in the ipsilateral testis
      at 14 days compared with control animals.

PMID- 14665964
TI  - Home Healthcare Nurses Forum held at NAHC meeting.

PMID- 14665965
TI  - 10 uses for personal digital assistants in home care.
AB  - This article focuses how clinical staff can use personal digital assistants
      (PDAs) to become more organized, expand quick reference libraries, and have some
      fun! If you've been wondering if a PDA will help maximize your work efficiently,
      this article is for you!

PMID- 14665966
TI  - The Joint Commission's requirements for evaluating contracted home care services.
AB  - Contracted services have gained greater emphasis in the home care standards and
      survey process over the past several years, especially as they relate to the
      quality and safety of the services provided. This column reviews 2004-2005
      standard LD.3.50, its applicable elements of performance, and discusses the Joint
      Commission's requirements for evaluating the care and services provided by
      contracted providers.

PMID- 14665967
TI  - Implementing evidence-based practice in home care.
AB  - As home care quality initiatives increase agencies must integrate evidence-based
      practice. This article reviews a model of quality improvement to guide system
      change that can be used to implement best evidence and suggests that most
      agencies fall within three stages of preparedness. Based on the stage of
      readiness, specific steps to move toward successful implementation of best
      practice are recommended.

PMID- 14665968
TI  - Agency characteristics most valued by home care nurses: findings of a nationwide
      study.
AB  - The demand for home care services is continuing to rise at such a rate that the
      home care nursing workforce will need to double by 2020. Struggling to recruit
      and retain an adequate clinician supply in the midst of a severe shortage,
      administrators may find help in the magnet hospital approach, which focuses on
      creating a professional practice environment. This study identified, in a
      national sample of home care nurses, organizational traits reported most
      important in supporting nurses' professional practice and job satisfaction.

PMID- 14665969
TI  - Collaboration of nursing and pharmacy in home infusion therapy.
AB  - This article explores the role of the home care nurse and the home infusion
      pharmacist in providing home infusion therapy. Ways to support collaboration,
      strategies to improve communication, and factors to consider when providing home
      infusion therapy are discussed.

PMID- 14665970
TI  - Using the seven A's to determine older adults' community resource needs.
AB  - Home care agencies cannot succeed under Medicare PPS unless clinicians
      efficiently assess and appropriately refer the elderly to community support
      systems. This article outlines how using the Seven A's (awareness, accessibility,
      affordability, appropriateness, adequacy, acceptability, and availability) can
      help nurses and agencies effectively determine the fit between older adults and
      community support agencies.

PMID- 14665971
TI  - Respecting the dying patient's rights.
AB  - Patients who are dying have unique needs and special rights. This article
      discusses eight basic rights for dying patients. It also gives examples of how
      hospice and home care providers can focus care to respect the dying patient's
      rights.

PMID- 14665972
TI  - Individualized education can improve foot care for patients with diabetes.
AB  - Providing individualized education to home care patients with diabetes can
      significantly improve their foot care practices. A nurse researcher from the
      Intercollegiate College of Nursing at Washington State University conducted a
      study of 40 home healthcare patients with Type 2 diabetes and found that an
      individualized educational intervention led to improved foot care knowledge, self
      care practices, and confidence performing foot related self-care.

PMID- 14665973
TI  - The nursing shortage: a name change is not the answer.

PMID- 14665974
TI  - Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse
      agonist AM251 in mice.
AB  - Psychopathological disorders, and depression in particular, are strongly linked
      to eating attitude in obese patients. The identification of cannabinoid CB1
      receptors (CB1Rs) in areas of the central nervous system (CNS) that have been
      implicated in regulation of mood and food intake suggests that these receptors
      may mediate such a behavioral link. The goal of this study was to evaluate CB1R
      modulation of antidepressant-like effects and food intake. For this purpose,
      129/SVE and C57BL/6 male mice were acutely dosed intraperitoneally (i.p.) with
      the CB1R inverse agonist AM251 (3-30 mg/kg) and tested, respectively, in the tail
      suspension test (TST) and in the forced-swim test (FST), which have been used
      widely as tests sensitive to antidepressant compounds. Like the antidepressant
      desipramine (DMI, 16 mg/kg), AM251 significantly reduced immobility at 10 mg/kg
      in the TST and at 1 and 10 mg/kg in the FST. Such a decrease of immobility was
      not accompanied by an increase in motor activity in the open field, suggesting
      that occupancy of CB1R by AM251 induced antidepressant-like effects. This was
      supported by two additional experiments. First, the co-administration of the CB1R
      agonist CP55940, at a dose that did not induce motor impairment or profound
      hypothermia (0.01 mg/kg), reversed effects of AM251 in the TST. Secondly, effects
      of AM251 in the FST were absent in CB1R knockout (KO) mice. In addition to an
      antidepressant-like effect, AM251 reduced fasting-induced hyperphagia over a
      comparable dose range. Taken together, these data suggest that regulation of mood
      and food intake might be obtained through inverse agonism of CB1R.

PMID- 14665975
TI  - The cannabinoid CB1 antagonists SR 141716A and AM 251 suppress food intake and
      food-reinforced behavior in a variety of tasks in rats.
AB  - Cannabinoid CB1 receptor agonists, including delta-9-tetrahydrocannabinol (Delta
      9-THC) (the main psychoactive ingredient in marijuana) have been shown to
      increase feeding in rats and humans. Conversely, it has been reported that acute
      administration of the CB1 receptor antagonist SR 141716A reduces food intake in
      rats. Based upon this observation, it has been suggested that CB1 antagonists
      could be useful as appetite suppressant drugs. The present studies were designed
      to provide a detailed examination of the effects of CB1 antagonists on food
      intake across a range of paradigms. Two CB1 antagonists (SR 141716A and AM 251)
      were administered to rats trained on fixed-ratio schedules with two different
      ratio requirements (fixed-ratio 1 and fixed-ratio 5). Both drugs produced a dose
      dependent decrease in lever pressing, and had a relatively long duration of
      action (T1/2: SR 141716A, 15.1 h; AM 251, 22.0 h). Furthermore, intake of three
      diets with differing macronutrient composition (lab chow, high fat, high
      carbohydrate) was studied. Both drugs significantly suppressed intake of all
      three foods, and there were no significant interactions between drug dose and
      diet type. These findings support the hypothesis that CB1 receptor antagonists
      could be useful pharmacological tools for the suppression of appetite.

PMID- 14665976
TI  - Selective effects of low-dose dopamine D1 and D2 receptor antagonists on rat
      information processing.
AB  - It is well established that the dopaminergic system influences simple reaction
      time (RT) performance. However, the role of this system in more complex
      information processing remains to be clarified. The present study was aimed at
      addressing this issue. To this end, we used an inferential method that relies on
      choice RT procedures and allows one to identify information processing stages in
      both humans and rats. Long-Evans rats responded to lateral visual cues (left or
      right). Two task factors, signal intensity and foreperiod duration, were
      manipulated. Low doses of two pharmacological agents, SCH 23390 (a D1 receptor
      antagonist; 0.015 and 0.025 micromol/kg) and eticlopride (a D2 receptor
      antagonist; 0.01 and 0.02 micromol/kg), were administrated systemically. Both
      drugs increased choice RT: eticlopride interacted with signal intensity on RT,
      showing that D2 receptors mediate at least the sensory stage of stimulus
      preprocessing. In addition, eticlopride interacted with signal intensity on
      omission rate, thereby suggesting an involvement of D2 receptors in attentional
      processes; and SCH 23390 interacted with foreperiod duration on RT, indicating
      that D1 receptors specifically mediate the response adjustment stage. The effect
      of this drug on RT rests entirely in its interaction with foreperiod duration,
      allowing us to conclude that this D1 antagonist affects the response adjustment
      stage while sparing all other processing stages.

PMID- 14665977
TI  - Effects of a 5-HT2 receptor agonist, DOI (2,5-dimethoxy-4-iodoamphetamine), and
      antagonist, ketanserin, on the performance of rats on a free-operant timing
      schedule.
AB  - This experiment examined the effect of a 5-HT2 receptor agonist DOI (2,5
      dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on temporal
      differentiation performance. Twelve rats were trained under the free-operant
      psychophysical procedure to press two levers (A and B) in 50-s trials in which
      sucrose reinforcement (0.6 mol/l, 50 microl) was provided intermittently for
      responding on A during the first half, and on B during the second half of the
      trial. Psychometric curves were derived from percent responding on B (%B),
      recorded in successive 5-s epochs of the trials; logistic functions were fitted
      to these data for the derivation of timing indices (T50 [time corresponding to
      %B=50%], epsilon [slope of the logistic curve], Weber fraction). Cumulative
      probability of switching in successive 5-s epochs was used to estimate the mean
      switching time, S50. DOI (0.0625, 0.125 and 0.25 mg/kg, s.c.) dose-dependently
      reduced T50 and S50. These effects of DOI (0.25 mg/kg) were antagonized by
      ketanserin (1.0 mg/kg). The results show that DOI alters temporal differentiation
      in the free-operant psychophysical procedure. The antagonistic effect of
      ketanserin indicates that the effect of DOI was probably mediated by 5-HT2A
      rather than 5-HT2C receptors, since ketanserin is relatively selective for 5-HT2A
      receptors. Comparison of these results with our previous findings with a 5-HT1A
      receptor agonist indicates that 5-HT1A and 5-HT2A receptors mediate qualitatively
      similar effects on temporal differentiation.

PMID- 14665978
TI  - The effects of 7-OH-DPAT, quinpirole and raclopride on licking for sucrose
      solutions in the non-deprived rat.
AB  - Pharmacological manipulations that alter dopamine (DA) at DA receptor subtypes
      produce reductions in feeding behaviour. What remains uncertain is the exact way
      in which these reductions in feeding are achieved as a consequence of differing
      drug actions at separate receptor subtypes. In this study our aim was to compare
      the anorectic effects of the preferential D3/D2 agonists 7-hydroxy-2-(di-n
      propylamino)tetralin (7-OH-DPAT) and quinpirole and the non-selective D2/D3
      antagonist raclopride on the microstructure of licking responses in non-deprived
      rats. In a 20-min test, trained adult, male hooded rats had access to one of
      three solutions: 1%, 3% or 10% sucrose. 7-OH-DPAT (0.1-1.0 mg/kg, i.p.),
      quinpirole (0.03-0.3 mg/kg, s.c.), raclopride (0.03-0.3 mg/kg, i.p.) or vehicle
      were injected 20 min prior to the start of the licking test. A lickometer
      recorded the timing of each lick, from which the microstructural parameters of
      bout frequency and bout duration were also computed. All compounds reduced the
      mean bout duration, while 7-OH-DPAT and raclopride also brought about a
      compensatory increase in bout number. Analysis of the licking rates over the test
      session showed that 7-OH-DPAT, quinpirole and raclopride decreased the initial
      rate, without affecting the rate of decline of licking. Changes in licking
      microstructure (i.e. initial rate of licking and mean bout duration) after the
      administration of 7-OH-DPAT, quinpirole and raclopride, are consistent with an
      action of these dopaminergic compounds to reduce palatability.

PMID- 14665979
TI  - Differences in morphine and cocaine reinforcement under fixed and progressive
      ratio schedules; effects of extinction, reacquisition and schedule design.
AB  - Opiate reinforcement was evaluated under a progressive ratio (PR) schedule often
      used for psychostimulant self-administration (termed 'PR 3-4' because the third
      response requirement was four lever presses) and three additional schedules that
      were modified to provide successively lower levels of difficulty by decreasing
      the steepness of response requirement progression (termed 'PR 9-4', 'PR 14-4',
      and 'PR 26-4' because a response requirement of four was reached with step
      numbers of 9, 14 and 26, respectively). With the exception of the PR 3-4
      schedule, all of the schedules supported morphine self-administration, and
      morphine self-administration during initial exposure and reacquisition did not
      differ by more than 10%. In contrast to morphine, cocaine was self-administered
      under the PR 3-4 schedule, with responding clearly exceeding levels during
      extinction. The PR 9-4 schedule was most suitable for morphine self
      administration because it provided an intermediate level of difficulty, which
      supported levels of self-administration that exceeded values obtained under
      extinction but were less than those observed under FR-1. Under the PR 9-4
      schedule, the number of self-administered injections of morphine was 61.5% of the
      number of injections obtained under a simple FR-1 schedule. This compares with a
      value of 21.0% for cocaine self-administration under the PR 3-4 schedule compared
      to an FR-1 schedule. These results show important differences in self
      administration behavior supported by morphine and cocaine, which are consistent
      with a lower reinforcing efficacy for opiates relative to psychostimulants.

PMID- 14665980
TI  - Haloperidol blocks the acquisition but not the retrieval of a conditioned
      sensitization to apomorphine.
AB  - The dopamine agonist apomorphine (apo) elicits stereotyped pecking bouts in
      pigeons, a response which increases with successive apo injections. The present
      study sought, first, to confirm the hypothesis that this sensitization arises
      through a Pavlovian conditioning driven by both external and internal cues; and,
      secondly, to advance the hypothesis that during this learning the dopaminergic
      activation only initiates a process that probably ends in glutamatergic synapse
      modifications. The conditioned nature of the sensitization to apo was examined in
      two separate experiments that compared context contingent and context
      uncontingent apo treatments. The role of dopaminergic mechanisms in the
      acquisition, maintenance and retrieval of sensitization-conditioned pecking was
      examined by administering the dopamine antagonist haloperidol (hal) either
      before, during or after apo sensitization treatments. A contingency between
      context and apo was found to be essential for the acquisition and retrieval of
      apo-sensitized pecking. A pretreatment with hal did not curtail a subsequent
      sensitization to apo. When hal was co-administrated with apo it suppressed the
      initial pecking response to apo and blocked the acquisition of sensitized
      responding. A pecking response normally observed when apo-sensitized pigeons are
      challenged with saline (sal) in the same cage in which they were sensitized, was
      also absent. When hal was co-administered with apo after the sensitization was
      complete this led at first to an only partial apo response suppression. When
      treated with hal in the same cage, already sensitized pigeons responded much as
      if they had been challenged with sal. The sensitization induced by apo was thus
      blocked by hal co-administered during acquisition, but during the maintenance or
      retrieval phase hal did not impair a previously sensitized responding. It is
      concluded that when pigeons are sensitized to apo, dopaminergic mechanisms are
      implicated in initiating the neural modifications that underlie the conditioned
      sensitization, but that they themselves are not importantly altered.

PMID- 14665981
TI  - Enhanced sensitivity to the antinociceptive effects of kappa opioids in
      naltrexone-treated rats: dose- and time-dependent effects.
AB  - The purpose of the present study was to examine sensitivity to the
      antinociceptive effects of kappa opioids during chronic treatment with the
      nonselective opioid antagonist naltrexone. In a warm-water tail-withdrawal
      procedure, rats were restrained and the latencies to remove their tails from
      water maintained at 50 and 55 degrees C were recorded. Prior to chronic
      treatment, spiradoline, U50,488 and (-)-pentazocine produced dose-dependent
      increases in tail-withdrawal latencies at both 50 and 55 degrees C. Chronic
      treatment with 3.0 mg/kg naltrexone twice daily (b.i.d.) failed to alter
      sensitivity to the antinociceptive effects of spiradoline when tested 24 h
      following naltrexone administration. When the maintenance dose of naltrexone was
      increased to 30 mg/kg b.i.d., sensitivity to the effects of spiradoline was
      reduced when tested 24 h after naltrexone administration, but enhanced when
      tested 48 h after naltrexone administration. Enhanced sensitivity was also
      observed to the antinociceptive effects of U50,488 and (-)-pentazocine when
      tested 48 h after chronic treatment with 30 mg/kg naltrexone. After termination
      of chronic treatment, sensitivity to the antinociceptive effects of spiradoline,
      U50,488 and (-)-pentazocine returned to that originally observed prior to
      naltrexone treatment. These data indicate that chronic naltrexone treatment
      enhances sensitivity to the antinociceptive effects of kappa opioids, and that
      this effect is both dose and time dependent.

PMID- 14665982
TI  - Src kinase activity is required for avoidance memory formation and recall.
AB  - Using 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-D]pyrimidine (PP2), a
      specific inhibitor of the Src family of tyrosine kinases, here we show a direct
      involvement of these enzymes in memory formation and recall. When infused into
      the CA1 region of the dorsal hippocampus, immediately or 30 min after training
      rats in a one-trial inhibitory avoidance task, PP2 but not its inactive analog 4
      amino-7-phenylpyrazol[3,4-D]pyrimidine (PP3), blocked short- (STM) and long-term
      memory (LTM) formation, as tested 2 or 24 h post-training, respectively. PP2 had
      no effect on STM when given at 60 min post-training or on LTM when administered
      at 60, 120 or 180 min after the training session, but blocked memory recall when
      infused into CA1 15 min before a LTM expression test. Hence, activity of the Src
      family of tyrosine kinases is required in the CA1 region of the rat dorsal
      hippocampus for the normal formation and retrieval of one-trial inhibitory
      avoidance memory.

PMID- 14665985
TI  - Thoracic surgery education--responding to a changing environment.

PMID- 14665986
TI  - A milestone in cardiovascular surgery.

PMID- 14665988
TI  - Clinical-pathologic conference in general thoracic surgery: pulmonary blastoma.

PMID- 14665989
TI  - Improving the allograft valve: does the immune response matter?

PMID- 14665990
TI  - Fetal cardiac surgery: simplicity versus success in a new frontier.

PMID- 14665991
TI  - Pre-stage II mortality after the Norwood operation: addressing the next
      challenge.

PMID- 14665992
TI  - Our surgical culture of blame: a time for change.

PMID- 14665993
TI  - No pain, much gain?

PMID- 14665994
TI  - Attenuation of postcardioplegia injury with inhibitors of the sodium-hydrogen
      exchanger.

PMID- 14665995
TI  - Right ventricular-pulmonary artery connection in stage 1 palliation of
      hypoplastic left heart syndrome.

PMID- 14665996
TI  - Improved pain control after cardiac surgery: results of a randomized, double
      blind, clinical trial.
AB  - OBJECTIVE: We sought to determine whether a continuous regional infusion of a
      local anesthetic delivered to the operative site would result in decreased levels
      of postoperative pain and narcotic requirements for patients who undergo a
      standard median sternotomy for cardiac surgery. METHODS: A double-blind,
      randomized, controlled trial was conducted at a single center. Patients who were
      undergoing elective coronary artery bypass graft surgery alone or combined with
      laser transmyocardial revascularization received bilateral intercostal nerve
      blocks with either ropivacaine or saline. At wound closure, 2 catheters with
      multiple side openings were inserted percutaneously and placed directly over the
      sternum. The same agent (ropivacaine vs saline) was then administered as a
      continuous regional infusion for 48 hours through an elastomeric pump.
      Requirements for postoperative systemic narcotic analgesics and pain assessment
      scores were recorded for 72 hours after the operation. Secondary outcome measures
      were hospital length of stay and pulmonary function test results. Pain scores and
      narcotic use on the second postoperative day were also compared to avoid the
      confounding influence of anesthesia administered at the time of the operation.
      RESULTS: The total amount of narcotic analgesia required by the ropivacaine group
      was significantly less than that of the control group (47.3 vs 78.7 mg,
      respectively; P =.038). The ropivacaine group required less narcotics on
      postoperative day 2 as well (15.5 vs 29.4 mg, P =.025). The mean overall pain
      scores for the ropivacaine group were significantly less than the mean overall
      scores for the normal saline group (1.6 vs 2.6, respectively; P =.005). Patients
      receiving ropivacaine had a mean length of stay of 5.2 days compared with 8.2
      days for patients in the normal saline group (P =.001). Excluding the data from
      outliers (length of stay = 39 days), the normal saline group mean length of stay
      was 6.3 days (P <.01). There was no difference in assessment of pulmonary
      function. CONCLUSION: Continuous delivery of local anesthetics significantly
      improved postoperative pain control while decreasing the amount of narcotic
      analgesia required in patients who underwent standard median sternotomy. There
      was also a significant decrease in hospital length of stay, which is likely to
      result in significant cost reductions.

PMID- 14665997
TI  - Long-term outcome after coronary artery bypass grafting in cardiogenic shock or
      cardiopulmonary resuscitation.
AB  - OBJECTIVES: Coronary artery bypass grafting carried out in patients in
      cardiogenic shock or receiving cardiopulmonary resuscitation is an infrequently
      performed procedure, disrupting the normal process with a dramatic early risk.
      These circumstances mandate an analysis of the benefit, including the early
      identification of the late survivors. METHODS: A consecutive series of patients
      undergoing coronary artery bypass grafting while in cardiogenic shock (n = 167)
      or while receiving cardiopulmonary resuscitation (n = 92) from August 1979 until
      August 2001 were studied by using time-related and multivariate methodologies and
      a common-closing-date follow-up methodology. The events leading to the
      preoperative condition were either a recent catheterization, recent coronary
      artery bypass grafting, recent percutaneous transluminal coronary angioplasty, an
      infarction at home, an infarction in the hospital, or an infarction after a
      recent infarction. RESULTS: The 1- and 10-year survival was 59% +/- 6% and 47% +/
      7%, respectively. A normal hazard of late death was observed beyond the
      protracted early hazard. Multivariate analysis of survival identified an
      increased risk in the presence of additional comorbidity, treated diabetes, a
      lower pH at entry into the operating theater, and the presence of triple-vessel
      disease. The discriminatory power for hospital mortality of the predictive
      variables was low (receiving operator characteristic range, 0.56-0.69). The 30
      day freedom from hospital discharge alive was 33% +/- 7%. The 8-day freedom from
      stroke was 94% +/- 3%, and 8-day freedom from mechanical univentricular or
      biventricular support was 87% +/- 5%. The 10-year freedom from cardiosurgical
      reintervention was 90% +/- 6%. CONCLUSIONS: Coronary artery bypass grafting in
      cardiogenic shock or during cardiopulmonary resuscitation has an extremely high
      and protracted periprocedural risk but is balanced by a satisfactory late
      survival. An early prediction of the hospital survivors is difficult.

PMID- 14665998
TI  - Preoperative and operative predictors of delayed neurologic deficit following
      repair of thoracoabdominal aortic aneurysm.
AB  - PURPOSE: Delayed neurologic deficit has been recognized in recent years as a
      source of morbidity following thoracic and thoracoabdominal aortic repair. We
      wanted to find risk factors specifically significant for delayed neurologic
      deficit. In this initial study we looked at preoperative and operative risk
      factors. METHODS: We performed 854 thoracoabdominal aortic repairs between
      February 1991 and May 2001. For this study we excluded 26 patients who died
      before postoperative neurologic status could be evaluated and 38 who had
      immediate neurologic deficit on initial postoperative evaluation, leaving 790
      consecutive patients. We evaluated a wide range of demographic, preoperative
      physiological and intraoperative data, using univariate and multivariable
      statistical analyses. RESULTS: Twenty-one of 790 (2.7%) patients had delayed
      neurologic deficit. Significant univariate predictors included preoperative renal
      dysfunction (odds ratio 5.9; P <.006), acute dissection (odds ratio 3.9; P <.05),
      extent II thoracoabdominal aorta (odds ratio 3.0; P <.03), and use of adjuncts
      (cerebrospinal fluid drainage and distal aortic perfusion; odds ratio 7.7; P
      <.03). The use of the adjuncts dropped from the multivariable model but all other
      factors remained. No other significant risk factors were identified. Twelve of 21
      (57%) patients recovered neurologic function with optimization of blood pressure
      and cerebrospinal fluid drainage. CONCLUSION: Preoperative renal dysfunction,
      acute dissection, and extent II thoracoabdominal aorta are significant predictors
      of delayed neurologic deficit. Previous studies have demonstrated that the use of
      adjuncts protects against immediate neurologic deficit. The findings of this
      study are consistent with the hypothesis that adjuncts reduce ischemic insult
      enough to prevent immediate neurologic deficit but that a period of increased
      spinal cord vulnerability persists several days postoperatively.

PMID- 14665999
TI  - Risk factors of mortality and permanent neurologic injury in patients undergoing
      ascending aortic and arch repair.
AB  - OBJECTIVES: To analyze outcome in elderly patients after surgical repair of the
      ascending aorta and the aortic arch as compared with their younger counterparts
      and to determine risk factors of mortality and permanent neurologic injury.
      Patients and methods Between January 1995 and February 2003, a total of 369
      patients underwent ascending aortic and arch repair. Indications for surgical
      intervention were acute type A dissections in 174 (47%) patients (<75 years, n =
      147; > or =75 years, n = 27) and chronic atherosclerotic aneurysms in 195 (53%)
      patients (<75 years, n = 168; > or =75 years, n = 27). Emergency surgery was
      performed in 167 (45%) patients; 202 patients (54.7%) underwent surgery requiring
      deep hypothermic circulatory arrest. Pre- and intraoperative factors were
      evaluated by means of stepwise logistic regression analysis to determine risk
      factors of mortality and permanent neurologic injury. RESULTS: Overall in
      hospital mortality was 11.6%. In-hospital mortality with regard to indication for
      surgical intervention was comparable in both age groups (type A dissection: <75
      years, 15.6%; > or =75 years, 18.5%; P =.731; chronic atherosclerotic aneurysm:
      <75 years, 7.7%; > or =75 years, 7.4%; P =.933). Permanent neurologic injury was
      observed in 5.0%. Permanent neurologic injury with regard to surgical
      intervention was comparable in both age groups (type A dissection: <75 years,
      8.8%; > or =75 years, 3.7%; P =.359; chronic atherosclerotic aneurysm: <75 years,
      3.0%; > or =75 years, 3.7%; P =.843). Stepwise logistic regression analysis
      revealed preoperative hemodynamic instability (odds ratio 4.3; P =.000), duration
      of cardiopulmonary bypass (odds ratio 2.1; P =.001), and permanent neurologic
      injury (odds ratio 1.7; P =.033) but not age as independent predictors affecting
      mortality. Utilization of but not duration of deep hypothermic circulatory arrest
      was the only independent predictor of permanent neurologic injury (odds ratio
      2.8; P =.019). CONCLUSIONS: Age shows a trend toward a higher risk of mortality
      but does not predict a higher incidence of permanent neurologic injury after
      ascending aortic and arch repair. As utilization of deep hypothermic circulatory
      arrest remains the only independent predictor of permanent neurologic injury,
      alternative approaches to maintain cerebral perfusion during ascending aortic and
      arch repair are warranted.

PMID- 14666000
TI  - In situ retrocaval skeletonized right internal thoracic artery anastomosed to the
      circumflex system via transverse sinus: technical aspects and postoperative
      outcome.
AB  - BACKGROUND: The aim of this study was to investigate whether, by using the in
      situ right internal thoracic artery via the transverse sinus (eventually
      retrocaval), both the proximal and distal major branches of the circumflex system
      could be grafted and to evaluate the early and late outcome in these patients.
      METHODS: Between January 1997 and March 2002, 452 consecutive patients underwent
      grafting of the circumflex system with the in situ skeletonized right internal
      thoracic artery routed via the transverse sinus. The mean age was 62.4 +/- 10.3
      years. A mean of 2.2 +/- 0.3 arterial grafts per patient were used, and 271 (60%)
      patients underwent total arterial myocardial revascularization. At 3 months after
      surgery, 86 patients (right Y or T graft) underwent echo color Doppler imaging
      before and after an adenosine provocative test. The mean follow-up was 27 +/- 8
      months. RESULTS: The success rate of skeletonized right internal thoracic artery
      grafting to the circumflex system branch was 100%. There were 15 (3.4%) hospital
      deaths. In 116 patients who underwent postoperative angiography, the total
      patency rates of the right and left internal thoracic arteries were 94% and
      96.6%, respectively. Strong predictors for nonfunctional internal thoracic artery
      grafts were a small internal thoracic artery caliber (P <.001), recipient
      coronary artery diameter less than 1.5 mm (P =.012), stenotic lesions of less
      than 60% (P =.016), and diffuse stenotic lesions (P =.015) of the recipient
      coronary artery. In 86 patients who underwent postoperative echo color Doppler
      imaging, the flow reserves at the main stem of the left and right internal
      thoracic arteries were 2.24 +/- 0.5 and 2.48 +/- 0.6, respectively. Cumulative
      actuarial survival at 3 years was 96.3%, and event-free cumulative survival was
      93%. The Cox model revealed a left ventricular ejection fraction of less than 35%
      (P =.016), age greater than 70 years (P =.025), New York Heart Association grade
      greater than III (P =.0019), nontotal arterial myocardial revascularization (P
      =.002), and the preoperative presence of more than 1 ischemic area (P <.001) as
      strong predictors for poor overall cumulative event-free survival. CONCLUSIONS:
      The skeletonized right internal thoracic artery, placed via the transverse sinus
      and eventually retrocaval, can reach most branches of the circumflex system and
      is associated with an excellent patency rate. The predictors for poor overall
      event-free survival seem to be similar to those of the general population
      undergoing conventional coronary artery bypass grafting. Use of bilateral
      internal thoracic arteries and in situ right internal thoracic artery grafting
      via the transverse sinus offers the possibility of various configuration
      constructions, making possible total arterial myocardial revascularization with a
      minimum number of arterial conduits.

PMID- 14666001
TI  - Skeletonization of bilateral internal thoracic artery grafts lowers the risk of
      sternal infection in patients with diabetes.
AB  - OBJECTIVE: Deep sternal wound infection is a dreaded complication of coronary
      artery bypass surgery, particularly in patients with diabetes. This study
      determines whether skeletonization of internal thoracic artery conduits compared
      with pedicled harvesting reduces the risk of deep sternal wound infection in
      patients with diabetes undergoing bilateral internal thoracic artery grafting.
      METHODS: We reviewed prospectively gathered data on all patients who have
      undergone coronary artery bypass grafting and received bilateral internal
      thoracic artery grafts at our institution since 1990. We compared patients with
      diabetes who received skeletonized (n = 79) versus conventional pedicled (n = 36)
      internal thoracic artery conduits. RESULTS: The proportion of patients taking
      insulin (19.0% vs 14.0% for skeletonized vs conventional grafts, respectively, P
      =.6) or oral hypoglycemic agents (68.4% vs 69.4%, P =.9), as well as the
      prevalence of type I diabetes (2.5% vs 8.3%, P =.18), were similar in both
      groups. Patients who received skeletonized grafts were more likely to receive a
      free rather than an in situ right internal thoracic artery graft (93.7% vs 30.6%,
      P <.001). The prevalence of deep sternal wound infection was significantly lower
      in patients who received skeletonized grafts compared with patients who received
      conventional grafts (1.3% vs 11.1%, P =.03). Patients in the skeletonized group
      were also less likely to develop any (superficial or deep) sternal wound
      infection postoperatively (5.1% vs 22.2%, P =.03). There was no significant
      difference in the prevalence of deep sternal wound infection between patients
      with diabetes who received skeletonized internal thoracic arteries and patients
      without diabetes who underwent conventional internal thoracic artery grafting (n
      = 578) (1.2% vs 1.6%, respectively, P =.8). CONCLUSIONS: Skeletonization of
      internal thoracic artery conduits lowers the risk of deep sternal wound infection
      in patients with diabetes undergoing bilateral internal thoracic artery grafting.
      We no longer consider diabetes a contraindication to bilateral internal thoracic
      artery grafting, provided the internal thoracic arteries are skeletonized.

PMID- 14666002
TI  - Survival after myocardial revascularization for ischemic cardiomyopathy: a
      prospective ten-year follow-up study.
AB  - OBJECTIVE: The aim was to prospectively analyze all-cause mortality, predictors
      of survival, and late functional results after myocardial revascularization for
      ischemic cardiomyopathy over a 10-year follow-up. METHODS: We prospectively
      studied 57 patients with stable coronary artery disease and poor left ventricular
      ejection function (<35%), enrolled between 1989 and 1994. Stress thallium was
      analyzed in 37 patients to identify reversible ischemia. To avoid patients with a
      stunned myocardium, we excluded those with unstable angina or myocardial
      infarction within the previous 4 weeks. Mean age of the patients was 67 +/- 8
      years, and 93% of patients were men. Mean left ventricular ejection fraction was
      0.28 +/- 0.04, 50% were in Canadian Cardiovascular Society angina class III-IV,
      and 65% were in New York Heart Association functional class III-IV. RESULTS:
      Operative mortality was 1.7% (1/57). The mean left ventricular ejection fraction
      (0.30) at 15 months postoperatively did not change from before operation (0.28, P
      =.09). There were 8 deaths at 1 year and 42 deaths over the course of the study,
      producing a survival of 82.5% at 1 year, 55.7% at 5 years, and 23.9% at 10 years
      (95% confidence interval: 14.6%-39.1%). Symptom-free survival was 77.2% at 1 year
      and 20.3% at 10 years. The leading cause of death was heart failure in 29%
      (12/42). Multivariate analysis showed that large reversible defects on stress
      thallium were associated with improved left ventricular ejection fraction at 1
      year (P =.01) but only male sex was associated with improved long-term survival
      (P =.036). CONCLUSIONS: Myocardial revascularization for ischemic cardiomyopathy
      is associated with good functional relief from the symptoms of angina initially
      and, to a lesser extent, heart failure. Revascularization may have the advantage
      of preserving the remaining left ventricular function. However, the long-term
      mortality remains high.

PMID- 14666003
TI  - Quantitative gated myocardial perfusion single photon emission computed
      tomography improves the prediction of regional functional recovery in akinetic
      areas after coronary bypass surgery: useful tool for evaluation of myocardial
      viability.
AB  - OBJECTIVE: Assessment of myocardial viability in akinetic areas is essential in
      surgery for ischemic heart disease, including coronary artery bypass grafting and
      left ventriculoplasty. The aim of this study is to evaluate the utility of
      quantitative indices of perfusion uptake, wall motion, and wall thickening of
      each region calculated by quantitative electrocardiogram-gated single photon
      emission computed tomography (SPECT) for prediction of functional recovery after
      coronary artery bypass grafting. METHODS: Forty patients scheduled for coronary
      artery bypass grafting were prospectively included. Electrocardiogram-gated SPECT
      was performed before and 1 week and 3 months after operation, and coronary
      angiography was performed before and after operation. The myocardium was divided
      into 9 segments and myocardial viability, assessed by improvement of the wall
      motion score using a cine mode display, and evaluated by radionuclide criteria
      (perfusion uptake, wall motion, wall thickening). Twenty-four segments with
      moderate hypokinesis and 14 segments with akinesis with patent grafts were
      assessed. RESULTS: All segments with moderate hypokinesis except 1 (96%) had
      improved wall motion scores postoperatively, whereas of 14 segments with akinesis
      only 7 segments (50%) had improved wall motion scores. The preoperative perfusion
      uptake in the improved segments was significantly higher than in the nonimproved
      segments (62.7% +/- 15.6% vs 46.4% +/- 24.5%, P =.01). There was a significant
      difference in wall motion between the improved and nonimproved segments (3.8 +/-
      2.2 mm vs 1.4 +/- 1.4 mm, P =.001), and the preoperative wall thickening of the
      improved segments was significantly higher than in the nonimproved segments
      (27.2% +/- 14.1% vs 8.2% +/- 10.3%, P <.0001). The optimal cutoff level of
      perfusion uptake was 50%, with the highest accuracy of 72%, and the optimal
      cutoff levels of wall thickening and wall motion were 10% and 1.5 mm, with the
      highest accuracies of 76% and 85%, respectively. CONCLUSION: The regional
      functional index calculated by electrocardiogram-gated SPECT indicated that wall
      thickening was well correlated with functional recovery compared with wall motion
      or perfusion uptake. This suggests that the wall thickening calculated by
      electrocardiogram-gated SPECT may be more useful to predict functional recovery
      than regional myocardial perfusion. Or, it could suggest that in addition to
      perfusion uptake, wall thickening could enhance the objective assessment of
      myocardial viability.

PMID- 14666004
TI  - Decreasing significance of left ventricular dysfunction and reoperative surgery
      in predicting coronary artery bypass grafting-associated mortality: a twelve-year
      study.
AB  - OBJECTIVES: Patients undergoing coronary artery bypass grafting are older and
      have greater comorbidity than those operated on previously. We evaluated the
      changes in the predictors of in-hospital mortality among patients undergoing
      coronary artery bypass grafting during the last 12 years. METHODS: Data on
      demographic characteristics, preoperative risk factors, operative variables, and
      hospital outcomes were collected prospectively for all patients undergoing
      isolated coronary artery bypass grafting at a single institution from January 1,
      1990, to December 31, 2001. To examine the effect of time on patient risk
      profiles and outcomes, we divided patients into three groups according to year of
      operation (1990-1993 n = 5171, 1994-1997 n = 5977, 1998-2001 n = 6893). RESULTS:
      In-hospital mortality declined from 2.4% (1990-1993) to 1.2% (1998-2001, P
      <.0001). Left ventricular dysfunction, increasing age, female gender,
      hypertension, diabetes, cardiogenic shock, congestive heart failure, peripheral
      vascular disease, reoperative coronary artery bypass grafting, left main disease,
      and urgent surgery independently predicted in-hospital mortality in the entire
      cohort of 18,041 patients. Severe left ventricular dysfunction was the most
      significant predictor of in-hospital mortality in the 12-year cohort, but it had
      a declining influence with time (1990-1993 odds ratio 7.1, 1994-1997 odds ratio
      5.1, 1998-2001 not statistically significant) because of improving outcomes.
      Reoperative coronary artery bypass grafting similarly decreased in significance
      as a predictor of mortality. Emergency coronary artery bypass grafting was
      performed less frequently in recent years, but the requirement for emergency
      surgery carried an increasing odds ratio for mortality. CONCLUSIONS: Despite
      increasing patient age and comorbidity, improvements in perioperative management
      have reduced the significance of severe left ventricular dysfunction and
      reoperative coronary artery bypass grafting but not emergency surgery as
      predictors of in-hospital mortality.

PMID- 14666005
TI  - Does antegrade blood cardioplegia alone provide adequate myocardial protection in
      patients with left main stem disease?
AB  - BACKGROUND: The optimum route for cardioplegia administration in patients with
      severe coronary disease is still under debate. This study compared clinical,
      echocardiographic, and biochemical results in patients with left main stem
      disease treated with 2 different strategies of myocardial protection. METHODS:
      Between March 2000 and November 2002, 148 consecutive patients with left main
      stem disease undergoing coronary artery bypass grafting were divided into 2
      groups according to the route of cardioplegia delivery: antegrade in 87 patients
      (group A) or antegrade followed by retrograde in 61 patients (group B).
      Electrocardiography, troponin I, MB-creatine kinase, and MB-creatine kinase mass
      were performed at 12, 24, 48, and 72 hours postoperatively. Echocardiography was
      performed preoperatively and before hospital discharge. Data were stratified in
      subgroups of patients with the following associated risk factors: left
      ventricular hypertrophy, diabetes, and right coronary stenosis. RESULTS: Groups
      were homogeneous in preoperative and intraoperative variables, apart from the
      higher incidence of unstable angina and severity of left main stem disease in
      group B. Hospital deaths, intensive therapy unit and hospital stay, perioperative
      acute myocardial infarction, and intraaortic balloon pump support were similar in
      both groups. Postoperative recovery of left ventricle ejection fraction and wall
      motion score index did not differ between the 2 groups. However, postoperative
      atrial fibrillation was higher in group A (P =.015), especially in patients with
      diabetes (P <.0001). Troponin I was significantly higher in group A from
      postoperative hours 12 to 72 (P <.01), and the same pattern was observed in
      patients with diabetes (P <.001), critical right coronary stenosis (P <.001), and
      left ventricle hypertrophy (P <.001). CONCLUSION: The combined route of
      intermittent blood cardioplegia allows better results in left main stem disease.
      Such data are confirmed even in risk subgroups.

PMID- 14666006
TI  - Double crisscross sternal wiring and chest wound infections: a prospective
      randomized study.
AB  - OBJECTIVE: We sought to assess the efficiency of 2 different sternal wiring
      techniques in preventing deep sternal wound infection or sternal instability.
      METHODS: Seven hundred patients were randomized to 2 different groups according
      to chest-closure techniques. Three hundred fifty patients who underwent a
      peristernal double crisscross wire closure were included in group X, whereas 350
      patients who underwent a standard transsternal closure were included in group T.
      After sternal closure, the technique for wound suturing was the same for both
      groups, namely triple-layer sutures up to the intracutaneous skin. All data were
      prospectively collected and entered in our institute database. RESULTS: The 2
      groups of patients were comparable for sex, age, preoperative risk factors, and
      operative procedures. The overall mortality rate was 4.3% in group X and 4.6% in
      group T. Postoperative morbidity and mortality were comparable between the 2
      groups, unlike for sternal wound complications. None of the patients included in
      group X had superficial or deep wound complications, whereas in group T 7 (2%)
      patients presented with a superficial sternal wound infection, 6 (1.7%) presented
      with a deep chest wound infection with sternal instability requiring re
      exploration (P <.05), and 3 presented with a sternal instability caused by
      sternum disruption without infection. Among patients with deep wound infection
      and sternal instability, 1 patient died, resulting in a mortality rate of 16.7%.
      CONCLUSIONS: The peristernal double crisscross wiring technique achieved a
      greater sternal stability, resulting in a lower incidence of wound infection in
      association with triple-layer closure of suprasternal tissues.

PMID- 14666007
TI  - Surgical radiofrequency ablation of both atria for atrial fibrillation: results
      of a multicenter trial.
AB  - BACKGROUND: The Cox maze procedure has shown to be effective in treating atrial
      fibrillation. Radiofrequency ablation, with a similar objective, has been used as
      an adjunct to conventional cardiac surgery for the treatment of atrial
      fibrillation in more than 20 centers in Australia and New Zealand since March
      2000. This is a report of those results. METHODS: One hundred thirty-two patients
      in 20 centers underwent radiofrequency ablation as an adjunct to conventional
      cardiac surgery, with a standardized lesion set created with a flexible, 7
      electrode, temperature-controlled probe (Cobra; EPTechnologies, San Jose, Calif).
      All data were entered into a central registry, with regular follow-up prompted by
      the registry cocoordinator. Each radiofrequency scar was made with standard
      parameters requiring 2 minutes of tissue coagulation at 80 degrees C to 85
      degrees C. Patients undergoing mitral procedures had radiofrequency ablation
      performed in the left atrium endocardially. Patients undergoing aortic valve
      replacement or coronary artery bypass surgery underwent epicardial radiofrequency
      ablation of the left atrium. Epicardial radiofrequency ablation lesions on the
      right atrium were common to both groups of patients. Preoperatively, 75% of the
      patients had chronic atrial fibrillation, 21% had paroxysmal atrial fibrillation,
      and 4% had flutter. Surgical procedures performed included mitral valve procedure
      in 60%, coronary artery bypass grafting in 14%, aortic valve replacement in 7%,
      and coronary artery bypass grafting plus aortic valve replacement in 4%. RESULTS:
      There were no major complications related to the use of radiofrequency ablation.
      There were no soft tissue or cardiac perforations. Ten patients were
      defibrillated into sinus rhythm within 3 months postoperatively. The freedom from
      atrial fibrillation was 84% at 3 months, 90% at 6 months, and 100% at 12 months.
      All patients at 12 and 18 months' follow-up were in sinus rhythm. There were no
      thromboembolic complications. CONCLUSIONS: Surgical radiofrequency ablation can
      be performed safely as an adjunct to conventional cardiac surgery. A standardized
      lesion set created by using similar temperature settings can be adopted in
      multiple centers and might be effective in treating atrial fibrillation. Data
      collection through a central registry has helped in monitoring the effectiveness
      of this new technique in a scattered population.

PMID- 14666008
TI  - Home surveillance program prevents interstage mortality after the Norwood
      procedure.
AB  - OBJECTIVE: To determine whether early identification of physiologic variances
      associated with interstage death would reduce mortality, we developed a home
      surveillance program. METHODS: Patients discharged before initiation of home
      surveillance (group A, n = 63) were compared with patients discharged with an
      infant scale and pulse oximeter (group B, n = 24). Parents maintained a daily log
      of weight and arterial oxygen saturation according to pulse oximetry and were
      instructed to contact their physician in case of an arterial oxygen saturation
      less than 70% according to pulse oximetry, an acute weight loss of more than 30 g
      in 24 hours, or failure to gain at least 20 g during a 3-day period. RESULTS:
      Interstage mortality among infants surviving to discharge was 15.8% (n = 9/57) in
      group A and 0% (n = 0/24) in group B (P =.039). Surveillance criteria were
      breached for 13 of 24 group B patients: 12 patients with decreased arterial
      oxygen saturation according to pulse oximetry with or without poor weight gain
      and 1 patient with poor weight gain alone. These 13 patients underwent
      bidirectional superior cavopulmonary connection (stage 2 palliation) at an
      earlier age, 3.7 +/- 1.1 months of age versus 5.2 +/- 2.0 months for patients
      with an uncomplicated interstage course (P =.028). A growth curve was generated
      and showed reduced growth velocity between 4 and 5 months of age, with a plateau
      in growth beyond 5 months of age. CONCLUSION: Daily home surveillance of arterial
      oxygen saturation according to pulse oximetry and weight selected patients at
      increased risk of interstage death, permitting timely intervention, primarily
      with early stage 2 palliation, and was associated with improved interstage
      survival. Diminished growth identified 4 to 5 months after the Norwood procedure
      brings into question the value of delaying stage 2 palliation beyond 5 months of
      age.

PMID- 14666009
TI  - Right ventricular to pulmonary artery conduit instead of modified Blalock-Taussig
      shunt improves postoperative hemodynamics in newborns after the Norwood
      operation.
AB  - OBJECTIVE: Perioperative mortality, prolonged postoperative recovery after the
      Norwood procedure, and mortality between stage I and stage II might be related to
      shunt physiology. A right ventricular to pulmonary artery conduit offers a banded
      physiology in contrast to a Blalock-Taussig shunt. The purpose of this study was
      to assess the hemodynamic differences and their consequences in the postoperative
      course between Norwood patients with a Blalock-Taussig shunt and those with a
      right ventricular to pulmonary artery conduit. METHODS: From October 1999 until
      May 2002, 32 unselected consecutive patients underwent a Norwood procedure at the
      General Hospital Linz. The first 18 patients received a Blalock-Taussig shunt. In
      the remaining 14 patients we performed a right ventricular to pulmonary artery
      conduit. Both groups were compared. RESULTS: The diastolic blood pressure was
      significantly higher in the right ventricular to pulmonary artery conduit group
      (P <.001). Despite a higher FIO(2), PO(2) levels tended to be lower in the first
      5 postoperative days. At the age of 3 months, catheterization laboratory data
      showed a lower Qp/Qs ratio in the same group (0.86 [0.78; 1] versus 1.55 [1.15;
      1.6]; P =.005) and a higher dp/dt (955 [773; 1110] vs 776 [615; 907]; P =.018).
      (Descriptive data reflect medians and quartiles [in brackets].) Hospital survival
      was 72% in the Blalock-Taussig shunt group versus 93% in the right ventricular to
      pulmonary artery conduit group. Mortality between stage I and stage II was 23% in
      the Blalock-Taussig shunt group versus 0% in the right ventricular to pulmonary
      artery conduit group. CONCLUSIONS: A higher diastolic blood pressure and a lower
      Qp/Qs ratio were associated with a more stable and efficient circulation in
      patients with a right ventricular to pulmonary artery conduit. More intensive
      ventilatory support was necessary during the first postoperative days. We did not
      note any adverse effects of the ventriculotomy on ventricular performance.

PMID- 14666010
TI  - Neurodevelopmental status at eight years in children with dextro-transposition of
      the great arteries: the Boston Circulatory Arrest Trial.
AB  - OBJECTIVES: Our goal was to determine which of the two major methods of vital
      organ support used in infant cardiac surgery, total circulatory arrest and low
      flow cardiopulmonary bypass, results in better neurodevelopmental outcomes at
      school age. METHODS: In a single-center trial, infants with dextrotransposition
      of the great arteries underwent the arterial switch operation after random
      assignment to either total circulatory arrest or low-flow cardiopulmonary bypass.
      Developmental, neurologic, and speech outcomes were assessed at 8 years of age in
      155 of 160 eligible children (97%). RESULTS: Treatment groups did not differ in
      terms of most outcomes, including neurologic status, Full-Scale or Performance IQ
      score, academic achievement, memory, problem solving, and visual-motor
      integration. Children assigned to total circulatory arrest performed worse on
      tests of motor function including manual dexterity with the nondominant hand (P
      =.003), apraxia of speech (P =.01), visual-motor tracking (P =.01), and
      phonologic awareness (P =.003). Assignment to low-flow cardiopulmonary bypass was
      associated with a more impulsive response style on a continuous performance test
      of vigilance (P <.01) and worse behavior as rated by teachers (P =.05). Although
      mean scores on most outcomes were within normal limits, neurodevelopmental status
      in the cohort as a whole was below expectation in many respects, including
      academic achievement, fine motor function, visual-spatial skills, working memory,
      hypothesis generating and testing, sustained attention, and higher-order language
      skills. CONCLUSIONS: Use of total circulatory arrest to support vital organs
      during heart surgery in infancy is generally associated with greater functional
      deficits than is use of low-flow cardiopulmonary bypass, although both strategies
      are associated with increased risk of neurodevelopmental vulnerabilities.

PMID- 14666011
TI  - The effect of duration of deep hypothermic circulatory arrest in infant heart
      surgery on late neurodevelopment: the Boston Circulatory Arrest Trial.
AB  - OBJECTIVES: Despite the technical advantages of total circulatory arrest for
      vital organ support during infant heart surgery, many centers have moved away
      from its use because of the demonstrated effects of circulatory arrest of long
      duration on neurodevelopmental outcomes. Our goal was to determine the functional
      form of the association between duration of circulatory arrest and risk of
      neurodevelopmental dysfunction. METHODS: From 1988 to 1992, in a single-center
      trial, infants with d-transposition of the great arteries underwent the arterial
      switch operation after random assignment to circulatory arrest or low-flow
      bypass. The alpha-stat method was used, and hematocrit on bypass was maintained
      at 20%. Developmental, neurologic, and speech outcomes were assessed at 8 years
      of age in 155 of 160 eligible children (97%). Outcomes selected for analysis were
      Full-Scale, Verbal, and Performance IQ, Reading and Mathematics Composite, time
      to complete the Grooved Pegboard (dominant hand), and the Mayo Test for Apraxia.
      RESULTS: Nonparametric regression and piecewise linear models indicated that
      neurodevelopmental outcomes were generally not adversely affected unless the
      duration of circulatory arrest exceeded a threshold of 41 minutes (95% 1-sided
      lower confidence limit of 32 minutes). CONCLUSIONS: We found that the effect of
      duration of total circulatory arrest on later neurodevelopmental outcomes is
      nonlinear, with little influence at shorter durations and with steadily worsening
      outcomes after longer durations of circulatory arrest. Because the effects of
      duration of circulatory arrest may vary according to diagnosis, age at surgery,
      and other bypass and perioperative variables, this study cannot ascertain a
      universally "safe" duration of total circulatory arrest.

PMID- 14666012
TI  - Antioxidant therapy with Salvia miltiorrhiza decreases plasma endothelin-1 and
      thromboxane B2 after cardiopulmonary bypass in patients with congenital heart
      disease.
AB  - OBJECTIVE: The endothelium-derived vasoconstrictor endothelin-1 is increased
      after cardiopulmonary bypass in children with congenital heart defects. This
      study determines whether antioxidant therapy with Salvia miltiorrhiza injection,
      an herb extract containing phenolic compounds, prevents the postoperative
      increase of endothelin-1. The relationship between endothelin-1 and the
      endothelium-derived prostacyclin (prostaglandin I2) and thromboxane A2
      postoperatively is also investigated. METHODS: Twenty children with congenital
      heart defects and pulmonary hypertension were randomly assigned to group A
      (placebo control, n=10) or B (200 mg/kg Salvia miltiorrhiza intravenously after
      anesthesia induction and at the time of rewarming, respectively; n =10) before
      cardiac surgery. Central venous blood samples were taken before operation (T(0)),
      10 (T(1)) and 30 minutes (T(2)) after starting cardiopulmonary bypass, 10 (T(3))
      and 30 minutes (T(4)) after aortic declamping, and 30 minutes (T(5)) and 24 hours
      (T(6)) after termination of cardiopulmonary bypass. Plasma lipid peroxidation
      product malondialdehyde, myocardial specific creatine kinase-MB activity,
      thromboxane B2, and 6-keto-prostaglandin F(1 alpha) (stable metabolites of
      thromboxane A2 and prostaglandin I2) were measured. RESULTS: Malondialdehyde
      increased significantly at T(1) in group A and remained significantly higher than
      in group B thereafter (P <.05). Malondialdehyde in group B did not significantly
      increase over time. At T(5), plasma creatine kinase-MB, thromboxane B2, and
      endothelin-1 in group B were lower than in group A (P <.05); malondialdehyde
      correlated significantly with creatine kinase-MB (r = 0.71, P =.0005). At T(6),
      endothelin-1 negatively correlated with the 6-keto-prostaglandin F(1
      alpha)/thromboxane B2 ratio (r = -0.64, P =.0025). CONCLUSION: Antioxidant
      therapy reduces myocardial damage and attenuates postoperative vasoactive
      mediator imbalance.

PMID- 14666013
TI  - Secretion of A-type and B-type natriuretic peptides into the bloodstream and
      pericardial space in children with congenital heart disease.
AB  - OBJECTIVE: To determine the secretion of A-type and B-type natriuretic peptides
      into the bloodstream and pericardial space in children with congenital heart
      disease. METHODS: Plasma and pericardial fluid samples were obtained from 77
      patients undergoing total correction for congenital heart disease. All patients
      underwent detailed right-sided and left-sided cardiac catheterization
      preoperatively. RESULTS: A-type natriuretic peptide levels in pericardial fluid
      were lower than those in plasma (33.0 +/- 23.1 versus 39.8 +/- 33.6 pg/mL, P
      <.05), and B-type natriuretic peptide levels in pericardial fluid showed marked
      elevations compared with those in plasma (231.9 +/- 305.6 versus 19.8 +/- 29.3
      pg/mL, P <.0001). The A-type and B-type natriuretic peptide levels in plasma
      correlated with those in pericardial fluid (R =.522, P <.0001; R =.595, P
      <.0001). For A-type and B-type natriuretic peptide levels in plasma, the relation
      with biventricular volume had the highest correlation (R =.669, P <.0001; R
      =.652, P <.0001). The patients with a pulmonary-to-systemic flow ratio greater
      than 2 (n = 19) had high levels of natriuretic peptides not only in plasma (58.3
      +/- 43.2, 40.5 +/- 49.4 pg/mL, P <.05) but also in pericardial fluid (44.4 +/-
      31.5, 287.2 +/- 198.5 pg/mL, P <.05), and higher correlation between A-type and B
      type natriuretic peptide plasma levels and left ventricular volume (R =.913, P
      <.0001; R =.787, P <.0001). CONCLUSIONS: B-type natriuretic peptide is secreted
      not only into the bloodstream but also into the pericardial space in children
      with congenital heart disease. Natriuretic peptide levels in plasma correlated
      well with biventricular volume. The left ventricle was considered to be the main
      source of secreted natriuretic peptides in the patients with a pulmonary-to
      systemic flow ratio greater than 2.

PMID- 14666014
TI  - Pulmonary atresia with intact ventricular septum: strategy based on right
      ventricular morphology.
AB  - OBJECTIVES: Management strategy for pulmonary atresia with intact ventricular
      septum is controversial. We treated patients with this anomaly according to a
      management protocol based on our quantitative assessment of right ventricular
      morphology (index of right ventricular development and right ventricle-tricuspid
      valve index). In the present study, we reviewed a 20-year experience of the
      surgical treatment at our institution to define guidelines for selecting the
      appropriate type of surgical procedure. METHODS: Between April 1981 and June
      2002, 45 consecutive patients with pulmonary atresia with intact ventricular
      septum underwent surgical treatment. Open transpulmonary valvotomy was performed
      in 27 patients and Blalock-Taussig shunt in 18 patients as the initial palliative
      procedure. Three patients who underwent a successful transpulmonary valvotomy
      alone in the neonatal period required no further operation. Definitive repair was
      performed in 32 patients. Biventricular repair was performed on 19 patients, one
      and a half ventricular repair in 3, and Fontan-type operation in 10. RESULTS:
      There were 1 early and 2 late deaths before the definitive operation in patients
      who underwent transpulmonary valvotomy. Two patients who had coronary artery
      interruption died 3 months and 13 years after the initial Blalock-Taussig shunt.
      There were 1 early and 2 late deaths after the definitive operation. Actuarial
      survival, including noncardiac death, was 91.1% at 5 years after the initial
      procedure and 81.5% at 10 years. CONCLUSIONS: We treated patients with pulmonary
      atresia with intact ventricular septum according to a management protocol based
      on our quantitative assessment of right ventricular morphology with good results.

PMID- 14666015
TI  - Staged repair of tetralogy of Fallot and diminutive pulmonary arteries with a
      fenestrated ventricular septal defect patch.
AB  - OBJECTIVES: Patients with tetralogy of Fallot and diminutive pulmonary arteries
      are at risk for suprasystemic right ventricular pressure and right ventricular
      failure after complete repair. We report the short-term outcome and medium-term
      follow-up after using a fenestrated ventricular septal defect patch as a
      component of staged repair in selected patients. METHODS: We reviewed 47 patients
      with tetralogy of Fallot and diminutive pulmonary arteries whose ventricular
      septal defect patch was fenestrated, either electively or as a rescue technique,
      at a single institution between 1984 and 2001. RESULTS: Early mortality was 10.6%
      and occurred only in patients who underwent rescue fenestration. Review of medium
      term follow-up (median, 39 months) revealed 4 late deaths; an additional 4
      patients experienced right ventricular failure despite fenestration. Most (7/8)
      of these late events occurred in patients who underwent planned fenestration.
      Excessive left-to-right shunt through the fenestration developed in only 2
      patients. CONCLUSIONS: Fenestrated patch closure of the ventricular septal defect
      in patients with tetralogy of Fallot and diminutive pulmonary arteries resulted
      in 10.6% early mortality. Used preemptively in selected patients, this technique
      is associated with no surgical mortality and a low incidence of excessive left-to
      right shunt (4%). Early survivors remain at risk for late death and right
      ventricular failure despite fenestration.

PMID- 14666016
TI  - Inhaled nitric oxide versus prostacyclin in chronic shunt-induced pulmonary
      hypertension.
AB  - OBJECTIVE: Cardiac surgery for congenital heart defects is commonly complicated
      by shunt-induced chronic pulmonary hypertension and associated acute hypertensive
      crises. To investigate the effects of vasodilators in chronic and acute pulmonary
      hypertension, we used the innominate artery to create a growing aortopulmonary
      shunt in young piglets. METHODS: Pulmonary hemodynamics and right ventricular
      function and their responses to hypoxia, intravenous prostacyclin, and inhaled
      nitric oxide were investigated after closure of the shunt by using pulmonary flow
      pressure relationships, pulmonary vascular resistance partitioning, pulmonary
      vascular impedance, and ventriculoarterial coupling expressed as the ratio of
      right ventricular end-systolic elastance to effective pulmonary arterial
      elastance. RESULTS: Shunt-induced pulmonary hypertension was associated with
      medial hypertrophy of pulmonary arteries, increased resistance, increased
      elastance, increased wave reflection, and preserved ventriculoarterial coupling.
      Hypoxic pulmonary vasoconstriction was blunted in the shunt group. Compared with
      prostacyclin, inhaled nitric oxide was a more effective vasodilator in the shunt
      group and in hypoxia. Effective pulmonary arterial elastance and right
      ventricular end-systolic elastance increased in chronic (shunt) and acute
      (hypoxic) hypertension and decreased with vasodilators, preserving a normal
      coupling. CONCLUSIONS: A growing aortopulmonary shunt in the young pig is a
      reliable model of chronic pulmonary hypertension, with medial hypertrophy,
      increased resistance, and increased elastance. In this model inhaled nitric oxide
      is a better pulmonary vasodilator than intravenous prostacyclin, with neither
      drug having a specific inotropic effect, and normal coupling is preserved in
      chronic and acute pulmonary hypertension.

PMID- 14666017
TI  - A new role for cardioplegic buffering: should acidosis or calcium accumulation be
      counteracted to salvage jeopardized hearts?
AB  - OBJECTIVES: Thirty minutes of unprotected ischemia produced a jeopardized heart
      that was treated with a blood cardioplegic solution containing the natural
      erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or
      7.2 (nonbuffered), and this was tested alone and after pretreatment with Na(+)
      H(+) exchange blockade (cariporide) to define their protective effects. METHODS:
      Twenty-four Yorkshire-Duroc pigs (27-34.5 kg) underwent 30 minutes of
      normothermic global ischemia, followed by 30 minutes of aortic clamping during
      protection with buffered (n = 12) or nonbuffered (n = 12) glutamate-aspartate
      enriched blood cardioplegic solution. Twelve hearts (6 buffered and 6
      nonbuffered) were pretreated with intravenous cariporide (5 mg/kg) 15 minutes
      before ischemia. RESULTS: Severe and comparable left ventricle dysfunction
      followed buffered or nonbuffered cardioplegia: Preload recruitable stroke work
      recovered to 56% +/- 21% and 45% +/- 20% of baseline levels; creatine kinase MB,
      conjugated dienes, and myeloperoxidase activity markedly increased; moderate
      myocardial edema occurred; and endothelin-1 increased 2-fold more than baseline
      values. Cariporide pretreatment caused a similar return of preload recruitable
      stroke work to 86% +/- 9% and 90% +/- 6% after buffered or nonbuffered
      cardioplegia (P <.05 vs nonpretreated groups), allowed only minor creatine kinase
      MB and conjugated diene changes, and reduced endothelin-1 release 3-fold compared
      with hearts without sodium-hydrogen exchange blockage. CONCLUSIONS: The severe
      ischemia-reperfusion injury of 30 minutes of normothermic ischemia is not altered
      by an acidic or alkalotic pH cardioplegic solution. Correction of damage is
      achieved by adding Na(+)-H(+) exchange blocker therapy before treatment with
      buffered and nonbuffered solutions; thus, sodium-hydrogen exchange inhibition
      plays a more vital role in recovery than pH management.

PMID- 14666018
TI  - Cartilaginous metaplasia and calcification in aortic allograft is associated with
      transforming growth factor beta 1 expression.
AB  - BACKGROUND: Calcification of homografts and vascular conduits is poorly
      understood. Mechanisms leading to calcification were studied in a rat model of
      aortic allografts. METHODS: Rat aortas from Lew1W (RT1(u)) were transplanted into
      Lew1A (RT1(a)). Animals were killed at 30 days and 180 days, and aortic grafts
      were removed and analyzed for histologic and immunohistologic studies. RESULTS:
      Intimal surface increased progressively over 6 months and was the site of
      important modifications. Intimal cellular population changed from a leukocyte
      (CD45, OX1-OX30)- and macrophage (CD68, ED-1)-based population at 30 days to
      predominantly alpha-smooth muscle actin-expressing cells at 180 days. At 180
      days, allografts were characterized by an abundant extracellular matrix composed
      of collagen and elastic fibers associated with extensive calcification (von Kossa
      staining) located in the intima and media. Osteoblastic activity was present in
      calcified lesion as shown by alkaline phosphatase activity. At 180 days, numerous
      chondrocytes (protein S100-positive and alpha-smooth muscle actin-negative) were
      present focally in the media. However, double immunostaining revealed that a
      cellular population within the media with a chondrocyte-like morphology was alpha
      smooth muscle actin-positive and S100-negative. Active form of transforming
      growth factor beta1 was expressed from 30 to 80 days in the medial and intimal
      layers. CONCLUSIONS: These observations suggest that alpha-smooth muscle actin
      positive cells within aortic allografts are eventually transformed to a
      chondrocyte-like structure, leading to vascular cartilaginous metaplasia
      associated with the expression of transforming growth factor beta1 and could be a
      potential pathway leading to extensive vascular wall calcification in allografts
      through endochondral ossification.

PMID- 14666019
TI  - The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary
      bypass.
AB  - OBJECTIVE: Neuropsychologic disorders are common after coronary artery bypass
      operations. Air microbubbles are identified as a contributing factor. A dynamic
      bubble trap might reduce the number of gaseous microemboli. METHODS: A total of
      50 patients undergoing coronary artery bypass operation were recruited for this
      study. In 26 patients a dynamic bubble trap was placed between the arterial
      filter and the aortic cannula (group 1), and in 24 patients a placebo dynamic
      bubble trap was used (group 2). The number of high-intensity transient signals
      within the proximal middle cerebral artery was continuously measured on both
      sides during bypass, which was separated into 4 periods: phase 1, start of bypass
      until aortic clamping; phase 2, aortic clamping until rewarming; phase 3,
      rewarming until clamp removal; and phase 4, clamp removal until end of bypass.
      S100 beta values were measured before, immediately after, and 6 and 48 hours
      after the operation and before hospital discharge. RESULTS: The bubble
      elimination rate during bypass was 77% in group 1 and 28% in group 2 (P <.0001).
      The number of high-intensity signals was lower in group 1 during phase 1 (5.8 +/-
      7.3 vs 16 +/- 15.4, P <.05 vs group 2) and phase 2 (6.9 +/- 7.3 vs 24.2 +/- 27.3,
      P <.05 vs group 2) but not during phases 3 and 4. Serum S100 beta values were
      equally increased in both groups immediately after the operation. Group 2
      patients had higher S100 beta values 6 hours after the operation and
      significantly higher S100 beta values 48 hours after the operation (0.06 +/- 0.14
      vs 0.18 +/- 0.24, P =.0133 vs group 2). Age and S100 beta values were correlated
      in group 2 but not in group 1. CONCLUSION: Gaseous microemboli can be removed
      with a dynamic bubble trap. Subclinical cerebral injury detectable by increases
      of S100 beta disappears earlier after surgical intervention.

PMID- 14666020
TI  - MCI-186 prevents spinal cord damage and affects enzyme levels of nitric oxide
      synthase and Cu/Zn superoxide dismutase after transient ischemia in rabbits.
AB  - OBJECTIVE: The mechanism of spinal cord injury is believed to be related to the
      vulnerability of spinal motor neuron cells against ischemia. We tested whether
      MCI-186, which is useful for treating ischemic damage in the brain, can protect
      against ischemic spinal cord damage. METHODS: After induction of ischemia, MCI
      186 or vehicle was injected intravenously. Cell damage was analyzed by observing
      the function of the lower limbs and by counting the number of motor neurons. To
      investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage,
      we observed the immunoreactivity of Cu/Zn superoxide dismutase, neuronal nitric
      oxide synthase, and endothelial nitric oxide synthase. RESULTS: MCI-186 eased the
      functional deficits and increased the number of motor neurons after ischemia. The
      induction of neuronal nitric oxide synthase was significantly reduced by the
      treatment with MCI-186. Furthermore, the increase in the induction of endothelial
      nitric oxide synthase and Cu/Zn superoxide dismutase was more pronounced.
      CONCLUSION: These results indicate that MCI-186 may protect motor neurons from
      ischemic injury by reducing neuronal nitric oxide synthase and increasing
      endothelial nitric oxide synthase. MCI-186 may be a strong candidate for use as a
      therapeutic agent in the treatment of ischemic spinal cord injury.

PMID- 14666021
TI  - Passive ventricular constraint to improve left ventricular function and mechanics
      in an ovine model of heart failure secondary to acute myocardial infarction.
AB  - OBJECTIVE: This study investigated the effects on global cardiac function and
      myocardial energetics of limiting progressive dilatation after infarction by
      means of a woven polyester jacket cardiac support device. We hypothesized that
      placement of the cardiac support device results in a decrease in myocardial wall
      stress and improvement in cardiac function and myocardial energetics. METHODS: To
      investigate the effect of passive constraint on left ventricular function and
      mechanics, a total of 10 sheep were studied with pressure-volume analysis and
      magnetic resonance imaging. A baseline study was followed by the creation of an
      anterior infarct. After 1 week, the animals underwent a second study. The cardiac
      support device was then placed over the epicardium in 5 sheep; the remaining
      animals served as controls. A terminal study was performed at 2 months after the
      infarct. RESULTS: The cardiac support device group at the terminal study
      exhibited a decrease in end-diastolic volume (control 110.3 +/- 19.8 mL vs
      cardiac support device 67.6 +/- 4.7 mL, P =.006) and an improved ejection
      fraction (control 15.5% +/- 5.7% vs cardiac support device 29.46% +/- 4.42%, P
      =.008) relative to the control group. Myocardial energetics were also enhanced in
      the cardiac support device group, as evidenced by the significant improvements in
      potential energy (control 2015 +/- 503 mL. mm Hg/beat vs cardiac support device
      885 +/- 220 mL. mm Hg/beat, P =.006), efficiency (control 39.4% +/- 13.6% vs
      cardiac support device 59.8% +/- 8.5%, P =.044), and oxygen consumption (control
      0.072 +/- 0.013 mL O(2)/beat vs cardiac support device 0.052 +/- 0.007 mL
      O(2)/beat, P =.034). CONCLUSION: Passive constraint with the cardiac support
      device after infarct prevents further remodeling and may stimulate reverse
      remodeling in heart failure secondary to acute myocardial infarction. These
      results suggest that in human beings placement of the cardiac support device
      after a large anterior myocardial infarction may be effective in halting the
      remodeling process that often leads to end-stage heart failure. If proved
      effective, placement of a cardiac support device after large heart attacks has
      the potential to decrease the incidence of heart failure that results after large
      myocardial infarctions.

PMID- 14666022
TI  - Fibrillation in patients subjected to coronary artery bypass grafting.
AB  - OBJECTIVE: Atrial fibrillation is the most frequently encountered postoperative
      arrhythmic complication after coronary artery bypass grafting. Ischemic
      preconditioning has proved a potent endogenous factor in suppressing ischemia
      reperfusion-induced arrhythmias. The protective effect of ischemic
      preconditioning on atrial fibrillation after coronary artery bypass grafting has
      not been studied. The purpose of the present study was to investigate whether
      ischemic preconditioning had an effect on postoperative atrial fibrillation in
      patients undergoing coronary artery bypass grafting. METHODS: Eighty-five
      patients undergoing coronary artery bypass grafting were randomized into ischemic
      preconditioning and control groups. Holter data from 24-hour electrocardiography
      were collected 1 day before the operation to the second postoperative day. Atrial
      fibrillation was registered as positive if any atrial fibrillation event
      occurred. RESULTS: The overall incidence of postoperative atrial fibrillation and
      sustained atrial fibrillation was 34.1% and 27.1%, respectively. The occurrence
      of atrial fibrillation was significantly lower in the ischemic preconditioning
      group (21.4% in patients undergoing ischemic preconditioning and 46.5% in control
      subjects, P =.015). Preoperative recent unstable angina did not influence the
      incidence of atrial fibrillation. Patients with atrial fibrillation had longer
      intensive care unit stays and compromised postoperative hemodynamic outcomes.
      Binary logistic regression analysis showed that ischemic preconditioning,
      preoperative mean heart rate, and postoperative pulmonary capillary wedge
      pressure were the independent predictors of atrial fibrillation. CONCLUSIONS:
      Postcoronary artery bypass grafting atrial fibrillation is associated with more
      complicated postoperative outcome. Higher preoperative heart rate and
      postoperative pulmonary capillary wedge pressure were the independent predictors
      of atrial fibrillation. Recent unstable angina is not related to the occurrence
      of postcoronary artery bypass grafting atrial fibrillation. Ischemic
      preconditioning significantly suppresses postcoronary artery bypass grafting
      atrial fibrillation, suggesting that ischemic preconditioning can be used as an
      effective prophylactic method for postoperative atrial fibrillation.

PMID- 14666023
TI  - The antioxidant N-acetylcysteine preserves myocardial function and diminishes
      oxidative stress after cardioplegic arrest.
AB  - OBJECTIVE: Oxidative stress contributes to myocardial ischemia-reperfusion
      injury. We hypothesized that administration of the antioxidant N-acetylcysteine
      would have beneficial effects on myocardial function after cardiopulmonary bypass
      and cardioplegic arrest. METHODS: Anesthetized dogs (n = 18) were instrumented
      with myocardial ultrasonic crystals and a left ventricular micromanometer.
      Systolic function was measured by preload recruitable stroke work. Myocardial
      tissue water was determined by microgravimetry. Treated animals received 100
      mg.kg(-1) N-acetylcysteine 10 minutes before initiation of cardiopulmonary bypass
      followed by 20 mg.kg(-1).h(-1) continuous infusion until 1 hour after
      cardiopulmonary bypass. After baseline, cardiopulmonary bypass and 2-hour
      crystalloid cardioplegic arrest was initiated, then reperfusion/rewarming for 40
      minutes and separation from cardiopulmonary bypass. Myocardial function
      parameters and myocardial tissue water were measured at 30, 60, and 120 minutes
      after cardiopulmonary bypass. Oxidative stress was measured by 8-isoprostane
      concentrations in the coronary sinus plasma. RESULTS: Preload recruitable stroke
      work did not decrease from baseline in the N-acetylcysteine group and was
      significantly greater in N-acetylcysteine group compared with controls at 30
      (104% +/- 9% vs 80% +/- 4%; P <.05) and 120 minutes (98% +/- 7% vs 79% +/- 4%; P
      <.05) after cardiopulmonary bypass. Concentrations of 8-isoprostane in the
      coronary sinus plasma of the control dogs were significantly higher 30 minutes
      after cardiopulmonary bypass compared with baseline but were unchanged in the N
      acetylcysteine group. Myocardial edema resolution was significantly greater in
      the N-acetylcysteine group at 30 minutes after cardiopulmonary bypass compared
      with control (-2.5% +/- 0.7% vs -0.3% +/- 0.5% myocardial tissue water; P <.05).
      CONCLUSIONS: Administration of the antioxidant N-acetylcysteine preserves
      systolic function and enhances myocardial edema resolution after cardiopulmonary
      bypass/cardioplegic arrest. Furthermore, oxidative stress was significantly
      reduced in the treated animals. Therefore, our findings support the hypothesis
      that oxidative stress is the main cause for myocardial dysfunction after ischemia
      reperfusion.

PMID- 14666024
TI  - Direct inhibition of the sodium/hydrogen exchanger after prolonged regional
      ischemia improves contractility on reperfusion independent of myocardial
      viability.
AB  - BACKGROUND: A mechanism for myocardial dysfunction after ischemia and reperfusion
      is Na(+)/H(+) exchanger activation. Although past in vivo models of limited
      ischemia and reperfusion intervals demonstrate that Na(+)/H(+) exchanger
      inhibition confers myocardial protection when administered at the onset of
      ischemia, the effect of Na(+)/H(+) exchanger inhibition on myocardial function
      after prolonged ischemia and reperfusion remains unknown. This investigation
      tested the hypothesis that Na(+)/H(+) exchanger inhibition instituted at
      reperfusion and after prolonged coronary occlusion in pigs would influence
      myocardial contractility independent of myocardial viability. METHODS: A coronary
      snare and sonomicrometry crystals were placed in pigs (n = 21, 32 kg). Coronary
      occlusion was instituted for 120 minutes followed by reperfusion for 180 minutes.
      At 105 minutes of ischemia, pigs were randomized to ischemia and reperfusion only
      (saline solution, n = 11) or Na(+)/H(+) exchanger inhibition (HOE-642, 3 mg/kg
      intravenously, n = 10). Myocardial injury was determined by tissue staining and
      measurement of plasma myocyte-specific enzymes. Myocardial contractility was
      determined by calculation of the regional end-systolic pressure-dimension
      relation (millimeters of mercury per centimeter) and by assessment of
      interregional shortening. RESULTS: Infarct size was not different between groups
      (39% +/- 6%, P =.26). Moreover, at 180 minutes of reperfusion, plasma troponin-I
      and creatine kinase MB values had increased to identical levels in the ischemia
      and reperfusion-only and Na(+)/H(+) exchanger inhibition groups (300 +/- 35 and
      50 +/- 6 ng/mL, respectively). At 90 minutes of ischemia, regional end-systolic
      pressure-dimension relation decreased from baseline (5.7 +/- 0.5 versus 2.7 +/-
      0.3, P <.05) in the area at risk. By 30 minutes of reperfusion, regional end
      systolic pressure-dimension relation decreased further in the ischemia and
      reperfusion-only group (1.6 +/- 0.2, P <.05), but improved with Na(+)/H(+)
      exchanger inhibition (4.4 +/- 0.7, P <.05). CONCLUSIONS: Na(+)/H(+) exchanger
      inhibition instituted at reperfusion improved contractility independent of
      myocardial viability as assessed by absolute infarct size and myocyte-specific
      enzyme release. Thus, modulation of Na(+)/H(+) exchanger activity in the setting
      of prolonged ischemia and reperfusion may hold therapeutic potential.

PMID- 14666025
TI  - Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory
      cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon
      aminocaproic acid and aprotinin.
AB  - OBJECTIVES: Aprotinin is a broad-spectrum serine protease inhibitor that has been
      shown to attenuate the systemic inflammatory response in patients undergoing
      cardiac surgery with cardiopulmonary bypass. Although epsilon-aminocaproic acid
      is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie,
      plasmin activity and D-dimer formation), its ability to influence proinflammatory
      cytokine production remains unclear. This study was designed to compare the
      effects of epsilon-aminocaproic acid and aprotinin on plasma levels of
      interleukin-6 and interleukin-8 during and after cardiopulmonary bypass. METHODS:
      Sixty patients were randomized in a double-blind fashion to receive epsilon
      aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens
      (loading dose, pump prime, and infusion). Arterial blood samples were collected
      before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer,
      interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated
      measures analysis of variance. RESULTS: Both epsilon-aminocaproic acid and
      aprotinin administration resulted in significant (P <.05) reductions in D-dimer
      and interleukin-8 levels compared with saline. These reductions in D-dimer and
      interleukin-8 levels did not differ between the 2 drug-treated groups. The effect
      of these two antifibrinolytic agents on interleukin-6 was qualitatively similar
      to that noted with interleukin-8 but did not reach statistical significance.
      CONCLUSIONS: When dosed in a similar manner, epsilon-aminocaproic acid seems to
      be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels
      in patients undergoing primary coronary artery bypass graft surgery. These data
      indicate that suppression of excessive plasmin activity or D-dimer formation or
      both may play an important role in the generation of proinflammatory cytokines
      during and after cardiopulmonary bypass.

PMID- 14666026
TI  - Physiological coagulation can be maintained in extracorporeal circulation by
      means of shed blood separation and coating.
AB  - OBJECTIVE: Conventional extracorporeal circulation results in an activation of
      coagulation cascades. Coating of extracorporeal circulation tubes as well as
      avoidance of shed blood recirculation have been shown to reduce these phenomena.
      We evaluated a new shed blood separation system (AVANT D 970) utilizing a coated
      cardiopulmonary bypass tube system (PHISIO). METHODS: Forty patients (62 +/- 10
      years) underwent isolated coronary revascularization. Four groups (n = 10/group)
      were defined: no extracorporeal circulation, conventional uncoated extracorporeal
      circulation, uncoated extracorporeal circulation with shed blood separation, and
      coated extracorporeal circulation with shed blood separation. Thrombin
      antithrombin complex and free Hb were analyzed and statistically compared.
      RESULTS: Conventional extracorporeal circulation exhibited the highest
      intraoperative activation of coagulation (thrombin-antithrombin complex:
      extracorporeal circulation, 31.1 +/- 15.8 microg/L; uncoated extracorporeal
      circulation with shed blood separation, 15.3 +/- 7.8 microg/L; coated
      extracorporeal circulation with shed blood separation, 8.1 +/- 4.8 microg/L; no
      extracorporeal circulation, 2.4 +/- 0.6 microg/L; P <.05 extracorporeal
      circulation vs all others) and red blood cell damage (free Hb: extracorporeal
      circulation, 16.8 +/- 11.4 micromol/L; uncoated extracorporeal circulation with
      shed blood separation, 10.3 +/- 3.5 micromol/L; coated extracorporeal circulation
      with shed blood separation, 6.8 +/- 2.9 micromol/L; no extracorporeal
      circulation, 3.4 +/- 1.1 micromol/L; P <.05 extracorporeal circulation vs no
      extracorporeal circulation, coated extracorporeal circulation with shed blood
      separation). Coated extracorporeal circulation with shed blood separation showed
      only slight activation and cell trauma, which did not differ significantly from
      no extracorporeal circulation. CONCLUSIONS: Combination of coating and avoidance
      of shed blood recirculation maintained physiological coagulation levels and
      markedly reduced red blood cell trauma in extracorporeal circulation procedures.
      These combined modalities may therefore offer an alternative for off-pump
      procedures in patients with contraindications for conventional extracorporeal
      circulation.

PMID- 14666027
TI  - N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in
      patients undergoing cardiac surgery: results of a randomized, double-blind,
      placebo-controlled clinical trial.
AB  - OBJECTIVE: Reactive oxygen species have been shown to contribute to myocardial
      stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8
      iso-prostaglandin-F(2)alpha and nitrotyrosine formation. We hypothesized that the
      reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen
      species-mediated myocardial stress in patients undergoing cardiac surgery.
      METHODS: Forty patients undergoing coronary artery surgery (mean age +/- SD, 66
      +/- 9 years; 9 women and 31 men) were randomized to receive either N
      acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion
      at 20 mg.kg(-1).h(-1), n = 20) or placebo (n = 20). Patients and clinical staff
      were blinded to group assignment. Transmural left ventricular biopsy specimens
      collected before and at the end of cardiopulmonary bypass were subjected to
      immunocytochemical staining against 8-iso-prostaglandin-F(2)alpha (primary
      measure) as an indicator for reactive oxygen species-mediated lipid peroxidation
      and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated
      tissue injury. Cardiomyocyte staining was quantitatively determined by using
      densitometry (in gray units). Global left ventricular function was measured on
      the basis of fractional area of contraction by using transesophageal
      echocardiography. RESULTS: Patient characteristics in both groups were
      comparable. The change in left ventricular cardiomyocyte staining (end of
      cardiopulmonary bypass--before cardiopulmonary bypass) differed significantly
      between groups for both primary measures: 8-iso-prostaglandin-F(2)alpha, -1.8 +/-
      7.5 gray units (mean +/- SD, N-acetylcysteine group) versus 5.0 +/- 4.1 gray
      units (placebo group; 95% confidence interval, 2.6-11.0, P =.003); nitrotyrosine,
      -6.4 +/- 10.0 gray units (N-acetylcysteine group) versus 9.2 +/- 8.4 gray units
      (placebo group; 95% confidence interval, 9.4-21.7, P <.001). Hemodynamics and
      clinical outcomes were comparable in both groups. CONCLUSIONS: Reactive oxygen
      species scavenging with N-acetylcysteine attenuates myocardial oxidative stress
      in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic
      arrest.

PMID- 14666028
TI  - Gene expression profile after cardiopulmonary bypass and cardioplegic arrest.
AB  - OBJECTIVE: This study examines the cardiac and peripheral gene expression
      responses to cardiopulmonary bypass and cardioplegic arrest. METHODS: Atrial
      myocardium and skeletal muscle were harvested from 16 patients who underwent
      coronary artery bypass grafting before and after cardiopulmonary bypass and
      cardioplegic arrest. Ten sample pairs were selected for patient similarity, and
      oligonucleotide microarray analyses of 12,625 genes were performed using matched
      precardiopulmonary bypass tissues as controls. Array results were validated with
      Northern blotting, real-time polymerase chain reaction, in situ hybridization,
      and immunoblotting. Statistical analyses were nonparametric. RESULTS: Median
      durations of cardiopulmonary bypass and cardioplegic arrest were 74 and 60
      minutes, respectively. Compared with precardiopulmonary bypass,
      postcardiopulmonary bypass myocardial tissues revealed 480 up-regulated and 626
      down-regulated genes with a threshold P value of.025 or less (signal-to-noise
      ratio: 3.46); skeletal muscle tissues showed 560 and 348 such genes, respectively
      (signal-to-noise ratio: 3.04). Up-regulated genes in cardiac tissues included
      inflammatory and transcription activators FOS; jun B proto-oncogene; nuclear
      receptor subfamily 4, group A, member 3; MYC; transcription factor-8; endothelial
      leukocyte adhesion molecule-1; and cysteine-rich 61; apoptotic genes nuclear
      receptor subfamily 4, group A, member 1 and cyclin-dependent kinase inhibitor 1A;
      and stress genes dual-specificity phosphatase-1, dual-specificity phosphatase-5,
      and B-cell translocation gene 2. Up-regulated skeletal muscle genes included
      interleukin 6; interleukin 8; tumor necrosis factor receptor superfamily, member
      11B; nuclear receptor subfamily 4, group A, member 3; transcription factor-8;
      interleukin 13; jun B proto-oncogene; interleukin 1B; glycoprotein Ib, platelet,
      alpha polypeptide; and Ras-associated protein RAB27A. Down-regulated genes
      included haptoglobin and numerous immunoglobulins in the heart, and factor H
      related gene 2, protein phosphatase 1, regulatory subunit 3A, and growth
      differentiation factor-8 in skeletal muscle. CONCLUSIONS: By establishing a
      profile of the gene-expression responses to cardiopulmonary bypass and
      cardioplegia, this study allows a better understanding of their effects and
      provides a framework for the evaluation of new cardiac surgical modalities
      directly at the genome level.

PMID- 14666029
TI  - Changes in left anterior descending coronary artery flow profiles after coronary
      artery bypass grafting examined by means of transthoracic Doppler
      echocardiography.
AB  - OBJECTIVE: We sought to investigate the changes of velocity profiles in the left
      anterior descending coronary artery after coronary artery bypass grafting using
      transthoracic Doppler echocardiography. METHODS: Forty-five patients who received
      a bypass graft to the left anterior descending coronary artery were studied.
      Before coronary artery bypass grafting, Doppler velocity profiles of the distal
      left anterior descending coronary artery were recorded with transthoracic Doppler
      echocardiography. Peak systolic velocity, mean systolic velocity, peak diastolic
      velocity, mean diastolic velocity, total velocity time integral, systolic
      velocity time integral, and diastolic velocity time integral were measured. Three
      weeks after coronary artery bypass grafting, left anterior descending coronary
      artery antegrade flow in the distal portion of the anastomosis was obtained by
      using the same method. Coronary angiography was performed before and 3 weeks
      after coronary artery bypass grafting. RESULTS: The overall success rate of
      measuring the left anterior descending coronary artery flow was 60.0%
      preoperatively and 80.0% postoperatively. In 25 patients, in whom all parameters
      were obtained both before and after coronary artery bypass grafting, the
      following increased significantly after coronary artery bypass grafting: peak
      systolic velocity (14.86 +/- 7.50 vs 25.07 +/- 17.02 cm/s, P =.0045), mean
      systolic velocity (9.86 +/- 5.42 vs 18.03 +/- 12.94 cm/s, P =.0026), peak
      diastolic velocity (24.26 +/- 12.54 vs 48.28 +/- 31.66 cm/s, P =.0021), mean
      diastolic velocity (14.94 +/- 6.65 vs 30.36 +/- 20.71 cm/s, P =.0022), diastolic
      velocity time integral (7.22 +/- 2.88 vs 15.55 +/- 10.39 cm, P =.0009), total
      velocity time integral (10.50 +/- 4.48 vs 19.27 +/- 12.63 cm, P =.0034), and
      diastolic-to-systolic velocity time integral ratio (3.09 +/- 1.53 vs 4.97 +/-
      2.75, P =.0044). Angiography showed graft patency and no significant change in
      left anterior descending coronary artery stenosis in all patients. CONCLUSIONS:
      Transthoracic Doppler echocardiography showed a significant increase in some
      parameters in left anterior descending coronary artery flow after coronary artery
      bypass grafting. Measurement of left anterior descending coronary artery flow by
      means of transthoracic Doppler echocardiography might be a noninvasive method to
      evaluate the effect of bypass grafting on the left anterior descending coronary
      artery.

PMID- 14666030
TI  - Transplantation of cryopreserved muscle cells in dilated cardiomyopathy: effects
      on left ventricular geometry and function.
AB  - OBJECTIVE: Cell transplantation to prevent congestive heart failure in patients
      with inherited dilated cardiomyopathy might require the use of noncardiac donor
      cells unaffected by the genetic defect and cryopreservation to permit cell
      storage until the time of transplantation. However, the effects of
      cryopreservation on peripheral muscle cells harvested from a cardiomyopathic
      recipient and their subsequent ability to restore cardiac structure and function
      after transplantation are unknown. METHODS: Skeletal myoblasts and vascular
      smooth muscle cells from cardiomyopathic hamsters (delta-sarcoglycan-deficient
      BIO 53.58 hamster) and age-matched normal donor hamsters were isolated, expanded
      in culture, and cryopreserved. After reanimation in culture, cell morphology and
      growth rate were assessed and compared with values seen in noncryopreserved
      cells. A total of 4 x 10(6) previously cryopreserved skeletal myoblasts (n = 10)
      and vascular smooth muscle cells (n = 10) harvested from cardiomyopathic donors
      were then transplanted into the left ventricles of 17-week-old BIO 53.58
      hamsters. Hearts injected with culture medium alone (n = 11) served as controls.
      Heart function was assessed 5 weeks after transplantation on a Langendorff
      apparatus, and left ventricular geometry was quantified by means of computerized
      planimetry. Staining with 5-bromo-2'-deoxyuridine identified the injected cells.
      RESULTS: Vascular smooth muscle cells from cardiomyopathic donors had an abnormal
      morphology and diminished growth rates in culture compared with vascular smooth
      muscle cells from normal donors. These markers of injury were exacerbated by
      cryopreservation. In contrast, vascular smooth muscle cells from normal donors
      and skeletal myoblasts from either cardiomyopathic or normal donors appeared
      normal in culture and were unaffected by cryopreservation. Both cryopreserved
      vascular smooth muscle cells and skeletal myoblasts from cardiomyopathic donors
      formed a viable muscle-resembling tissue that prevented wall thinning, limited
      left ventricular dilatation, and preserved global systolic function in hamsters
      with a genetic dilated cardiomyopathy. However, attenuation of cardiac remodeling
      and preservation of global heart function was greater after skeletal myoblast
      transplantation compared with vascular smooth muscle cell transplantation in
      parallel to the in vitro morphologic and growth characteristics of these cells.
      CONCLUSIONS: Cryostorage of healthy donor cells does not prevent the benefits of
      cell transplantation on limiting remodeling and preserving cardiac function in
      the failing heart. The health of donor cells in vitro predicts their subsequent
      benefits on cardiac structure and function after transplantation.
      Cryopreservation of donor cells might facilitate a clinically applicable and
      effective approach for ventricular restoration with cell-transplantation therapy
      for patients with inherited dilated cardiomyopathy.

PMID- 14666031
TI  - Pretreatment with phenoxybenzamine attenuates the radial artery's vasoconstrictor
      response to alpha-adrenergic stimuli.
AB  - BACKGROUND: Although the radial artery bypass conduit has excellent intermediate
      term patency, it has a proclivity to vasospasm. We tested the hypothesis that
      brief pretreatment of a radial artery graft with the irreversible adrenergic
      antagonist phenoxybenzamine attenuates the vasoconstrictor response to the
      vasopressors phenylephrine and norepinephrine compared with the currently used
      papaverine/lidocaine. METHODS: Segments of human radial artery grafts were
      obtained after a 30-minute intraoperative pretreatment with a solution containing
      20 mL of heparinized blood, 0.4 mL of papaverine (30 mg/mL), and 1.6 mL of
      lidocaine (1%). The segments were transported to the laboratory and placed into a
      bath containing Krebs-Henseleit solution and 10, 100, or 1000 micromol/L
      phenoxybenzamine or vehicle. The segments were tested in organ chambers for
      contractile responses to increasing concentrations of phenylephrine and
      norepinephrine (0.5-15 micromol/L). RESULTS: Contractile responses to 15
      micromol/L phenylephrine in control radial artery segments averaged 44.2% +/-
      9.1% of the maximal contractile response to 30 mmol/L KCl. Papaverine/lidocaine
      modestly attenuated contraction to 15 micromol/L phenylephrine (32.1% +/- 5.9%; P
      =.22), but 1000 micromol/L phenoxybenzamine completely abolished radial artery
      contraction (-7.2% +/- 4.4%; P <.001). The effect of 10 and 100 micromol/L
      phenoxybenzamine on attenuating vasocontraction was intermediate between 1000
      micromol/L phenoxybenzamine and papaverine/lidocaine. Responses to 15 micromol/L
      norepinephrine in control radial artery segments averaged 54.7% +/- 7.5% of
      maximal contraction to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated
      the contraction response of radial artery segments (35.6% +/- 5.1%; P =.04). In
      contrast, 1000 micromol/L phenoxybenzamine showed the greatest attenuation of
      norepinephrine-induced contraction (-10.5% +/- 2.0%; P <.001). CONCLUSIONS: A
      brief pretreatment of the human radial artery bypass conduit with 1000 micromol/L
      phenoxybenzamine completely attenuates the vasoconstrictor responses to the
      widely used vasopressors norepinephrine and phenylephrine. Papaverine/lidocaine
      alone did not block vasoconstriction to these alpha-adrenergic agonists.

PMID- 14666033
TI  - Combined use of off-pump techniques and a sutureless proximal aortic anastomotic
      device reduces cerebral microemboli generation during coronary artery bypass
      grafting.
AB  - OBJECTIVE: Intraoperative cerebral microemboli are associated with the
      development of postoperative stroke and neurocognitive decline in patients
      undergoing coronary artery bypass grafting. Although cardiopulmonary bypass is
      responsible for the generation of a significant number of such emboli, the
      elimination of cardiopulmonary bypass alone has not been conclusively shown to
      improve neurocognitive outcome. The current study was performed to determine the
      effects of combined off-pump coronary artery bypass grafting and sutureless
      proximal aortic anastomotic techniques on the generation of intraoperative
      cerebral microemboli compared with standard coronary artery bypass grafting
      techniques of cardiopulmonary bypass and hand-sewn proximal anastomoses. METHODS:
      Fifty-three patients underwent off-pump coronary artery bypass grafting by using
      the sutureless Symmetry aortic connector device (St Jude Medical, St Paul, Minn)
      for all proximal anastomoses. Eighteen of these patients received intraoperative
      transcranial Doppler ultrasonography to determine right- and left-sided cerebral
      microembolic counts. These results were compared with those obtained from a
      similar group of 17 patients undergoing standard coronary artery bypass grafting,
      in whom cardiopulmonary bypass and hand-sewn proximal anastomoses were used.
      RESULTS: Our use of the proximal anastomotic device in patients undergoing
      coronary artery bypass grafting was safe, with no aortic complications,
      postoperative strokes, or in-hospital deaths. Microembolic counts to both the
      right and left cerebral circulation were significantly reduced in the patients
      undergoing off-pump coronary artery bypass grafting (right = 21.9 +/- 20.7
      emboli, left = 24.9 +/- 19.2 emboli) compared with those in patients undergoing
      standard coronary artery bypass grafting (right = 181.6 +/- 85.3, left = 189.9 +/
      60.401, P <.0001). CONCLUSIONS: Our use of a sutureless proximal anastomotic
      device during off-pump coronary artery bypass grafting is safe and significantly
      decreases cerebral microembolism when compared with standard coronary artery
      bypass grafting with cardiopulmonary bypass and hand-sewn anastomoses. Long-term
      follow-up is needed to determine the effects of this technical strategy on
      neurocognitive outcome.

PMID- 14666032
TI  - Evaluation of a novel sutureless anastomotic connector: from endothelial function
      to mid-term clinical and angiographic follow-up.
AB  - OBJECTIVES: We evaluated the effect of the St Jude Medical sutureless anastomotic
      connector on endothelium-dependent and -independent saphenous vein graft
      relaxation, as well as on clinical outcomes and graft patency in patients.
      METHODS: Human saphenous vein grafts were assigned to control or connector groups
      (loaded for 1 or 5 minutes; n = 18). Isometric dose-response curves to
      endothelium-dependent and -independent (sodium nitroprusside) vasodilators were
      constructed in saphenous vein grafts precontracted with phenylephrine. Thrombin
      mediated vasorelaxation, an early determinant of saphenous vein graft failure,
      was also evaluated. Percent maximum relaxation was compared between groups.
      Patients in whom the St Jude Medical connector was employed underwent clinical
      follow-up, stress tests, and angiography 6 to 12 months postoperatively. RESULTS:
      A23187-induced endothelium-mediated relaxation, sodium nitroprusside-induced
      endothelium-independent relaxation, and thrombin-mediated vasorelaxation did not
      differ between control and connector saphenous vein grafts at either time point
      studied. Twenty-seven patients received St Jude Medical connectors. There was no
      hospital mortality; patients were followed for 679 +/- 241 days. There was 1 late
      death; the connector saphenous vein graft was patent at postmortem. All connector
      saphenous vein grafts were patent at follow-up angiography. Four grafts had
      stenoses (30%-60%), without symptoms or requirement for intervention. All hand
      sewn saphenous vein grafts were also patent. CONCLUSIONS: The St Jude Medical
      connector does not impair endothelium-dependent vasorelaxation. In patients,
      patency of the connector saphenous vein grafts 6 to 12 months postoperatively was
      100% but 22% of grafts had non-flow-limiting stenoses at or near the connector.
      Further long-term studies are required to confirm the safety of the St Jude
      Medical connector with regards to endothelial function and restenosis.

PMID- 14666034
TI  - Magnetic vascular coupling for distal anastomosis in coronary artery bypass
      grafting: a multicenter trial.
AB  - OBJECTIVE: The hand-sewn anastomosis is the "gold standard" for performing
      coronary artery bypass grafts. However, performing a hand-sewn anastomosis is
      more demanding and time-consuming when used in less invasive approaches such as
      small access, totally endoscopic or beating heart surgery. In conjunction with
      attempts to reduce the surgical trauma of coronary artery bypass grafts by using
      these less invasive approaches, alternative methods for constructing distal
      anastomoses should be explored. These data report on predischarge angiographic
      findings and 30-day clinical follow up of patients who have received a new distal
      anastomotic device. METHODS: In a multicenter trial, 32 patients (mean age: 65 +/
      9 years; 85% men) requiring multivessel coronary artery bypass surgery had 1 of
      the anastomoses performed using a novel anastomotic technology. The Magnetic
      Vascular Positioner System was used in 1 of the bypass grafts and the other
      bypasses were completed by conventional hand-sewn technique. The Magnetic
      Vascular Positioner System consists of 4 magnetic, gold-plated implants and 2
      delivery devices that facilitate the creation of a functional end-to-side
      anastomosis. A predischarge angiogram was performed to evaluate graft patency.
      RESULTS: There were no device-related major adverse events. The application of
      the Magnetic Vascular Positioner device was successful in 32 of 41 cases (78%).
      Nine patients were intended for treatment but did not receive the Magnetic
      Vascular Positioner System. In 5 of the cases the coronary artery was too small;
      1 case had a posterior wall plaque in the target artery; and 3 patients had a
      nonhemostatic anastomosis after coupling of the port and were subsequently
      converted to hand-sewn anastomoses. The median total Magnetic Vascular Positioner
      anastomotic time was 137 seconds with a range from 65 to 370 seconds. Overall
      patency rate of the Magnetic Vascular Positioner anastomosis was 93.5% versus
      91.7% (P = not significant) in hand-sewn grafts. One patient (3.1%) died due to
      low cardiac output but had patent grafts at autopsy. One myocardial infarction
      (3.1%) occurred the day after a percutaneous transluminal coronary angioplasty of
      a hand-sewn graft. One prolonged mechanical ventilation (3.1%) was required
      because of pneumonia and adult respiratory distress syndrome. CONCLUSIONS:
      Magnetic vascular coupling in coronary surgery is safe and effective and has
      acceptable early patency rates. This new technique may facilitate beating heart
      and minimally invasive coronary artery bypass grafts.

PMID- 14666035
TI  - Facilitated endoscopic beating heart coronary artery bypass grafting using a
      magnetic coupling device.
AB  - BACKGROUND: Suturing of a coronary anastomosis in totally endoscopic coronary
      artery bypass grafting on the beating heart is technically demanding. The
      potential benefits of the endoscopic Magnetic Vascular Positioner device
      (Ventrica, Inc, Fremont, Calif) to facilitate construction of a coronary
      anastomosis in a closed chest environment were evaluated. METHODS: Totally
      endoscopic coronary artery bypass grafting on the beating heart was performed in
      8 foxhound-beagle inbred dogs with the da Vinci telemanipulation system
      (Intuitive Surgical, Mountain View, Calif). A prototype of the endoscopic
      Magnetic Vascular Positioner device was used to facilitate construction of the
      coronary anastomosis. One pair of magnets was inserted in the internal thoracic
      artery and left anterior descending artery using robotic instruments to guide and
      place the endoscopic delivery platform. All animals underwent angiography; gross
      inspection of the anastomotic site was performed after excision of the hearts.
      RESULTS: The procedure was accomplished in all animals in 169 minutes (155-190
      minutes). Dissection of the left anterior descending coronary artery (6.5
      minutes; 1-20 minutes), positioning of the stabilizer (8.5 minutes; 7-16
      minutes), placement of occlusion tapes (6 minutes, 3-10 minutes), and arteriotomy
      5.5 minutes (3-30 minutes) was achieved without problems. By use of the Magnetic
      Vascular Positioner device, the anastomosis at the graft site was performed with
      the graft still in situ. Except for 1 premature deployment, all other deployments
      were easily accomplished in 3 minutes (1-28 minutes). The following adverse
      events were encountered: bleeding from the right ventricle caused by occlusion
      tape (1), anastomotic leakage on reperfusion requiring repair stitches (2), and
      anastomotic occlusion as a result of thrombus (1). All except 1 animal with a
      patent graft and anastomosis survived the procedure. The overall patency was 7 of
      8. DISCUSSION: The combination of robotic technology allowing for dexterous
      manipulation in a closed chest environment and a simple yet effective and
      timesaving technique for anastomotic coupling may facilitate beating heart
      totally endoscopic coronary artery bypass grafting.

PMID- 14666037
TI  - Histogram analysis of computed tomography numbers of clinical T1 N0 M0 lung
      adenocarcinoma, with special reference to lymph node metastasis and tumor
      invasiveness.
AB  - PURPOSE: To predict lymph node metastasis and tumor invasiveness in lung
      adenocarcinoma from computed tomography findings, we examined computed tomography
      number histograms of clinical T1 N0 M0 lung adenocarcinomas. PATIENTS AND
      METHODS: Histograms of pixel computed tomography numbers were made for 100
      patients with clinical T1 N0 M0 lung adenocarcinoma. Pathological tumor stages
      were N0 in 80 patients, N1 in 7, N2 in 9, and T4 due to intrapulmonary metastasis
      in 4. RESULTS: The histogram showed 3 patterns: 1 peak at a low computed
      tomography number (n = 18), 1 peak at a high computed tomography number (n = 54),
      and 2 peaks at both low and high computed tomography numbers (n = 28).
      Histologically, adenocarcinoma with 1 peak at a low computed tomography number
      showed a large area of bronchioloalveolar carcinoma-like spread with little area
      of solid growing tumor or central fibrosis, whereas those with 1 peak at a high
      computed tomography number showed a large area of solid growing tumor or central
      fibrosis with little bronchioloalveolar carcinoma-like spread. Adenocarcinomas
      with 2 peaks had both types of areas. Lymph node or pulmonary metastases were
      seen in none (0%) of the adenocarcinomas with 1 peak at a low computed tomography
      number, in 1 (4%) with 2 peaks, and in 20 (37%) with 1 peak at a high computed
      tomography number. The former 2 types had metastases less frequently than those
      with 1 peak at a high computed tomography number (P <.01). In the 79 patients
      with pathological T1 N0 M0, tumor involvement of the intratumoral vessels or
      pleura was seen in 1 of 18 (6%) adenocarcinomas with 1 peak at a low computed
      tomography number, which was significantly less frequent than the 18 of 34 (53%)
      with 1 peak at a high computed tomography number (P <.001) and 10 of 27 (37%)
      with 2 peaks (P <.05). CONCLUSION: Clinical T1 N0 M0 adenocarcinomas with 1 peak
      at a low computed tomography number on histogram seldom had lymph node metastasis
      or tumor involvement of vessels or pleura. Limited surgical resection could be
      indicated for this type of adenocarcinoma, especially for elderly patients or
      patients with poor pulmonary function.

PMID- 14666036
TI  - Extrapleural regional versus systemic analgesia for relieving postthoracotomy
      pain: a clinical study of bupivacaine compared with metamizol.
AB  - BACKGROUND: The effects of a local anesthetic delivered through a catheter
      inserted in the extrapleural region by a surgeon and an analgesic agent given
      systemically on pain after thoracotomy were assessed. METHODS: The patients in
      group I (n = 25) had a catheter inserted between the parietal pleura and the
      endothoracic fascia by a surgeon, and 0.5% bupivacaine was given through this
      catheter. Another 25 patients (group II) had metamizol given intravenously.
      Respiratory function tests, arterial blood gases, range of shoulder motion, and
      postoperative pain were evaluated for each group. Bupivacaine and metamizol were
      given just before finishing the thoracotomy and then repeated every 4 hours for 3
      days. RESULTS: There was no statistical difference in arterial blood gases
      between the groups (P >.05). There were statistically significant differences in
      the respiratory function tests, range of shoulder motion, and visual analogue
      scale (P <.05) between the groups. Group I had fewer complications than group II.
      There was no mortality in either group. CONCLUSIONS: Bupivacaine given through a
      catheter to the extrapleural region before finishing thoracotomy is substantially
      beneficial for the prevention of postoperative pain and reduction of
      postoperative complications.

PMID- 14666038
TI  - Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced
      esophageal carcinoma.
AB  - OBJECTIVE: We sought to determine whether chemoradiotherapy after esophagectomy
      improves survival. METHODS: From 1994 to 2000, 31 patients with locoregionally
      advanced esophageal carcinoma (90% pT3, 81% pN1, and 13% pM1a) received
      postoperative adjuvant chemoradiotherapy. Concurrently, 52 patients with advanced
      carcinoma underwent esophagectomy alone and survived at least 10 weeks, the time
      frame for adjuvant therapy. A propensity score based on demographic, tumor, and
      surgical factors was used to identify matched pairs to determine the association
      of adjuvant therapy with outcomes. RESULTS: For patients receiving adjuvant
      therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year
      survivals were 28 versus 14 months, 68% +/- 8.4% versus 60% +/- 6.8%, and 44% +/-
      9.0% versus 17% +/- 5.6%, respectively (P =.05). Similarly, risk-unadjusted
      median time to recurrence was 25 versus 13 months (P =.15), and median recurrence
      free survival was 22 versus 11 months (P =.04). Among propensity-matched
      patients, median, 1-year, and 4-year survivals for those receiving adjuvant
      therapy versus esophagectomy were 28 versus 15 months, 60% +/- 11.0% versus 65%
      +/- 10.7%, and 44% +/- 11.3% versus 0% (P =.05). Median time to recurrence was 25
      versus 13 months (P =.04), and recurrence-free survival was 22 versus 10 months
      (P =.02). CONCLUSION: In patients with locoregionally advanced esophageal
      carcinoma, addition of postoperative adjuvant chemoradiotherapy to esophagectomy
      alone doubled survival time, time to recurrence, and recurrence-free survival.
      Patients with locoregionally advanced carcinoma after esophagectomy should be
      considered for adjuvant therapy.

PMID- 14666039
TI  - Resection of multifocal non-small cell lung cancer when the bronchioloalveolar
      subtype is involved.
AB  - OBJECTIVE: Bronchioloalveolar lung cancer is commonly multifocal and can also
      present with other non-small cell types. The staging and treatment of multifocal
      non-small cell cancer are controversial. We evaluated the current staging of
      multifocal bronchioloalveolar carcinoma and the therapeutic effectiveness of
      resection when this tumor type is involved. METHODS: We reviewed our experience
      between 1992 and 2000 with complete pulmonary resections for bronchioloalveolar
      carcinoma. Kaplan-Meier survival curves were calculated from the dates of
      pulmonary resection. RESULTS: Among 73 patients with bronchioloalveolar
      carcinoma, 14 patients, 7 male and 7 female with a mean age of 65 years (51-87
      years), had multifocal lesions without lymph node metastases. Follow-up was 100%
      for a median of 5 years (range 2.6-8.5 years). Tumor distribution was unilateral
      in 9 patients and bilateral in 5 patients. The multifocal nature of the disease
      was discovered intraoperatively in 4 patients. Nine patients had 2 lesions, 4
      patients had 3 lesions, and 1 patient had innumerable discrete foci in a single
      lobe. Operative mortality was 0. Postoperatively, 10 patients were staged pIIIB
      or pIV on the basis of multiple foci of similar morphology; 4 patients had some
      differences in histology (implying multiple stage 1 primaries). The median
      survival time to death from cancer was 14 months (141 days-5.6 years). The
      overall 5-year survival after resection of multifocal bronchioloalveolar
      carcinoma was 64%. Unilateral or bilateral distribution had no impact on
      survival. CONCLUSIONS: The current staging system is not prognostic for
      multifocal bronchioloalveolar carcinoma without lymph node metastases. Complete
      resection of multifocal non-small cell lung cancer when bronchioloalveolar
      carcinoma is a component may achieve survivals similar to that of stage I and II
      unifocal non-small cell lung cancer. When bronchioloalveolar carcinoma is
      believed to be one of the cell types in multifocal disease without lymph node
      metastases, consideration should be given to surgical resection.

PMID- 14666040
TI  - Preoperative chemotherapy for esophageal cancer with paclitaxel and carboplatin:
      results of a phase II trial.
AB  - OBJECTIVE: Paclitaxel has one of the highest response rates when used as a single
      agent in patients with esophageal cancer. The combination of paclitaxel and
      carboplatin has been shown to be a well-tolerated and safe regimen in non-small
      cell lung cancer. The objective of this study was to determine the efficacy of
      preoperative paclitaxel and carboplatin in patients with carcinoma of the
      esophagus. PATIENTS AND METHODS: A phase II trial was initiated in January 1999
      and concluded in January 2001. All patients had potentially resectable disease
      (including clinical T4 lesions). Patients with stage I disease and those with
      visceral metastases were excluded. All underwent preoperative computed tomography
      scanning and endosonography for staging. Paclitaxel (200 mg/m(2)) and carboplatin
      (area under the curve = 6) were given on days 1 and 22. Esophagectomy was carried
      out on weeks 6 to 8. RESULTS: Twenty-six (11 epidermoid, 15 adenocarcinoma)
      patients completed the trial. Median age was 61.5 and 85% were men. Preoperative
      staging showed: stage IIA, 6 patients; stage IIB, 1 patient; and stage III, 19
      patients. All patients completed their preoperative chemotherapy. There was no
      unexpected chemotherapy-related toxicity. A major clinical response was achieved
      in 16 patients (61%: 19% complete, 42% partial). Resectability was 77% (20/26). A
      complete pathologic response was seen in 11% of all patients and in 25% of those
      with epidermoid cancer. Hospital mortality and morbidity were 4 and 27%,
      respectively. Overall 3-year survival was 48% (64% for resected patients, median
      not reached). All 6 unresectable patients died within 6 months of exploration.
      CONCLUSION: Paclitaxel-carboplatin combination is a safe and well-tolerated
      regimen for esophageal cancer with clinical response rates comparable to
      historical controls. This regimen may be especially suitable for patients with
      epidermoid cancer, who had a 25% pathological complete response in this report.

PMID- 14666041
TI  - Cisplatin augments cytotoxic T-lymphocyte-mediated antitumor immunity in poorly
      immunogenic murine lung cancer.
AB  - OBJECTIVE: Many tumors are poorly immunogenic and resistant to cytotoxic T
      lymphocyte-mediated cell lysis. Because cisplatin has been demonstrated to
      increase tumor cell Fas receptor expression, we hypothesized that cisplatin will
      enhance cytotoxic T-lymphocyte tumor cell killing and augment the antitumor
      effect of an active immunotherapy strategy in a poorly immunogenic murine lung
      cancer model. METHODS: Lewis lung carcinoma cells were exposed to cisplatin in
      vitro, and Fas receptor expression and apoptosis in response to an agonistic anti
      Fas antibody were quantified using flow cytometry. Wild-type and Fas ligand
      deficient mice bearing Lewis lung carcinoma flank tumors were then treated with
      intraperitoneal cisplatin as well as an intratumoral injection of an adenovirus
      gene transfer vector encoding CD40 ligand. End points included tumor size, animal
      survival, and Fas expression (determined using immunofluorescence). Cytotoxicity
      assays were performed using splenocytes from adenovirus gene transfer vector
      encoding CD40 ligand-treated animals as effectors and cisplatin-treated Lewis
      lung carcinoma cells as targets. RESULTS: Cisplatin induced heightened expression
      of Fas receptor on Lewis lung carcinoma cells in vitro and in vivo and enhanced
      apoptosis in cells exposed to an agonistic anti-Fas antibody. In vivo, the
      combination of 1 dose of intraperitoneal cisplatin and intratumoral adenovirus
      gene transfer vector encoding CD40 ligand inhibited tumor growth and prolonged
      survival compared with adenovirus gene transfer vector encoding CD40 ligand
      alone, resulting in a higher cure rate. This effect was lost in Fas ligand
      deficient mice. Splenocytes from adenovirus gene transfer vector encoding CD40
      ligand-treated wild-type mice lysed cisplatin-treated Lewis lung carcinoma cells
      more efficiently than untreated Lewis lung carcinoma cells, an effect lost in
      splenocytes from Fas ligand-deficient mice. CONCLUSION: Cisplatin augments the
      antitumor effect of a cytotoxic T-lymphocyte-mediated immunotherapy strategy,
      resulting in a higher cure rate than seen with immunotherapy alone. This effect
      is associated with the enhanced ability of cytotoxic T lymphocytes to lyse tumor
      cells that have been exposed to cisplatin through Fas/Fas ligand interactions.

PMID- 14666042
TI  - Efficacy and safety of single-trocar technique for minimally invasive surgery of
      the chest in the treatment of noncomplex pleural disease.
AB  - OBJECTIVE: To assess the efficacy and the safety of a single-trocar technique for
      minimally invasive surgery of the chest in the management of multiple noncomplex
      thoracic diseases, a prospective study was performed and the results are
      presented. METHODS: Between October 1998 and December 2001, 100 patients
      underwent video-assisted thoracic surgery through a single trocar. The patients
      were divided into 4 groups as follows: (1) benign, (2) malignant, (3) pleural
      effusion, and (4) empyema. The following data were analyzed: age, sex, forced
      vital capacity, forced expiratory volume in 1 second, percentage of the predicted
      forced expiratory volume in 1 second, type of anesthesia, anesthesia time,
      surgery time, intraoperative complications, morbidity, chest tube removal,
      hospital stay, and follow-up. RESULTS: The patient population consisted of 64 men
      and 36 women with a mean age of 62 years (range 31-92 years). General anesthesia
      was used in 53 patients (25 double-lumen and 28 single-lumen tube) and local
      anesthesia and sedation in 47 patients. Talc pleurodesis was performed in 55
      patients. Mean operative time was 65 +/- 37 minutes, 48 +/- 18 minutes for simple
      and 67 +/- 37 minutes (P =.004) for complex pleural effusion. Mean anesthesia
      time was 102 +/- 85 minutes. Chest tubes were removed after 5 +/- 2 days. Mean
      overall hospital stay was 6 +/- 3 days, 5 +/- 2 days for benign diseases, 7 +/- 3
      days for malignant diseases, and 8 +/- 3 for empyema. Morbidity was present in 19
      patients. Two patients had intraoperative bleeding; 1 required a mini-thoracotomy
      to control it. There was no hospital mortality. Three patients had wound
      infection, and no patient with malignant diseases had port site metastasis.
      CONCLUSION: Video-assisted thoracic surgery through a single trocar is simple,
      effective, and beneficial for all patients in the diagnosis and treatment of
      noncomplex diseases of the chest. Furthermore, with this newest type of
      technologically advanced instrumentation it is possible to carry out simple
      intrathoracic procedures without using additional ports.

PMID- 14666043
TI  - Prolonged donor ischemic time does not adversely affect long-term survival in
      adult patients undergoing cardiac transplantation.
AB  - OBJECTIVE: With liberalization of donor eligibility criteria, organs are being
      harvested from remote locations, increasing donor ischemic times. Although
      several studies have evaluated the effects of prolonged donor ischemic times on
      short-term survival and graft function, few have addressed concerns regarding
      long-term survival. METHODS: Over the last 11 years, 819 consecutive adults
      underwent cardiac transplantation at Columbia Presbyterian Medical Center.
      Recipients were separated into the following 4 groups based on donor ischemic
      time: <150 minutes, 150 to 200 minutes, 200 to 250 minutes, and >250 minutes.
      Statistical analysis included Kaplan-Meier survival and Cox proportional hazard
      models to identify predictors of long-term survival. RESULTS: Donor ischemic time
      was 120.1 +/- 21.1 minutes for group 1 (n = 321), 174.1 +/- 14.7 minutes for
      group 2 (n = 264), 221.7 +/- 14.6 minutes for group 3 (n = 154), and 295.5 +/-
      37.1 minutes for group 4 (n = 80) (P <.001). There were no significant
      differences in recipient age, donor age, etiology of heart failure, United
      Network for Organ Sharing status, or history of previous cardiac surgery among
      the groups (P = NS). Prolonged donor ischemic time did not adversely affect long
      term survival, with actuarial survival at 1, 5, and 10 years of 86.9%, 75.2%, and
      56.4% for group 1; 86.2%, 76.9%, and 50.9% for group 2; 86.4%, 71.0%, and 43.7%
      for group 3; and 86.7%, 70.1%, and 50.9% for group 4 (P =.867). There was no
      significant difference in freedom from transplant coronary artery disease among
      the 4 groups (P =.474). CONCLUSIONS: Prolonged donor ischemic time is not a risk
      factor for decreased long-term survival. Procurement of hearts with prolonged
      donor ischemic time is justified in the setting of an increasing recipient pool
      with a fixed donor population.

PMID- 14666045
TI  - Resistance to aspirin after external ventricular assist device implantation.

PMID- 14666046
TI  - Doppler microembolic signals during cardiac surgery: comparison between arterial
      line and middle cerebral artery.

PMID- 14666047
TI  - Should HIV-positive recipients undergo heart transplantation?

PMID- 14666048
TI  - Should lungs from donors with severe acute pulmonary embolism be accepted for
      transplantation? The Hannover experience.

PMID- 14666044
TI  - Implantation of a left ventricular assist device and the hub-and-spoke system in
      treating acute cardiogenic shock: who survives?

PMID- 14666049
TI  - Isolated persistent fifth aortic arch with systemic-to-pulmonary arterial
      connection.

PMID- 14666050
TI  - Anomalous origin of the left coronary artery from the main pulmonary artery
      associated with Berry syndrome.

PMID- 14666051
TI  - Successful Fontan procedure for asplenia with pulmonary atresia and major
      aortopulmonary collateral arteries.

PMID- 14666052
TI  - Closed correction of systemic semilunar valve insufficiency in the neonate.

PMID- 14666053
TI  - Aortic arch repair with a working beating heart in premature infants.

PMID- 14666054
TI  - Unroofed coronary sinus syndrome: diagnosis, classification, and surgical
      treatment.

PMID- 14666055
TI  - Single-finger subcutaneous defibrillation lead and "active can": a novel
      minimally invasive defibrillation configuration for implantable cardioverter
      defibrillator implantation in a young child.

PMID- 14666056
TI  - Study design in valve surgery and outcome.

PMID- 14666057
TI  - Esophageal perforation during left atrial radiofrequency ablation: is the risk
      too high?

PMID- 14666058
TI  - Atrioesophageal fistula: is it an unavoidable complication of radiofrequency
      ablation?

PMID- 14666059
TI  - Authors should list confounding factors and alternative explanations for adverse
      events seen with new technologies.

PMID- 14666060
TI  - Pattern of lymphatic spread and prognosis in pN1 non-small cell lung cancer: what
      does it stand for?

PMID- 14666061
TI  - Influence of chromosome 22q11.2 microdeletion on surgical outcome after treatment
      of tetralogy of fallot with pulmonary atresia.

PMID- 14666062
TI  - Caveat against the use of feiba in combination with recombinant factor viia.

PMID- 14666063
TI  - Is there an evidence in favor of off-pump coronary artery bypass?

PMID- 14666064
TI  - Short esophagi and a long career.

PMID- 14666065
TI  - Problems with complication rate analysis.

PMID- 14666066
TI  - Safety of bronchoplastic resection after induction therapy for lung cancer.

PMID- 14666067
TI  - Lack of evidence for vitamin C as acute vasodilator.

PMID- 14666068
TI  - Exhaled nitric oxide and cardiac surgery with extracorporeal circulation.

PMID- 14666069
TI  - Enhance learning with an audience response system.

PMID- 14666070
TI  - Vision for the orthodontist CEO.

PMID- 14666071
TI  - Financial management: five steps to producing effective financial statements.

PMID- 14666072
TI  - Developing, implementing, and sustaining a marketing plan.

PMID- 14666073
TI  - Transverse molar movements during growth.
AB  - The purpose of this study was to evaluate changes in molar crown torque and
      intermolar arch width from the time of permanent first molar eruption to early
      adulthood. Molar crown torque and intermolar arch width were measured in 36
      untreated subjects with Class I occlusion from the Iowa Facial Growth Study at
      approximate ages 7.5, 10.3, 12.9, 16.5, and 26.4 years. On average, the
      mandibular first and second molars uprighted buccally by 5.0 degrees and 7.5
      degrees, respectively. Mandibular first and second molar intermolar width
      increased by 2.2 and 0.78 mm, respectively. On average, maxillary first and
      second molars uprighted lingually by 3.3 degrees and 5.9 degrees, respectively.
      Maxillary first and second intermolar width increased by 2.8 and 2.0 mm,
      respectively. Results of statistical analysis by the Wilcoxon signed rank test
      indicate that (1) maxillary molars erupt with buccal crown torque and upright
      with age, whereas mandibular molars erupt with lingual crown torque and upright
      with age (P <.01), and (2) molar crown torque changes are accompanied by
      concurrent increases in maxillary and mandibular intermolar width (P <.01).

PMID- 14666074
TI  - Retained deciduous mandibular molars in adults: a radiographic study of long-term
      changes.
AB  - Management of retained deciduous second molars in the absence of permanent
      successors can be challenging. The purpose of this retrospective radiographic
      study was to examine long-term changes in retained deciduous mandibular second
      molars in adult patients. Specifically, we sought to answer the question, "If an
      adult has a retained deciduous mandibular second molar and a missing successor,
      is retaining the deciduous molar a viable treatment option?" From more than 6000
      adult patients at the University of Iowa College of Dentistry, 20 were identified
      who initially had at least 1 retained deciduous mandibular second molar without a
      permanent successor and who had radiographs spanning 5 or more years after the
      initial visit. The mean (standard deviation) age at the initial examination was
      36.1 (12.9) years, the mean age at the final examination was 48.5 (12.6) years,
      and the mean examination time span was 12.4 (7.7) years. Of the 28 retained
      deciduous molars initially identified, 24 (86%) continue to function. The
      remaining 4 were lost at a mean age of 51.0 (13.9) years and a mean time span
      after initial examination of 14.3 (10.0) years; this approximates the lifespan of
      some prosthetic appliances. These 4 mandibular deciduous molars were lost because
      of caries or periodontal breakdown. Furthermore, we found that the average
      shortening of all deciduous root lengths was negligible (0.16 mm), and only 6
      teeth underwent a change in restoration status. Based on this study in adults and
      earlier studies in adolescents, we conclude that retaining healthy deciduous
      mandibular second molars is a viable treatment alternative.

PMID- 14666075
TI  - Occurrence of malocclusion and need of orthodontic treatment in early mixed
      dentition.
AB  - This study analyzed the occlusions of 489 children at the onset of the mixed
      dentition period (mean age 5.1 years, range 4.0-7.8 years). These children
      participate in an ongoing clinical trial that is investigating the effects of
      orthodontic intervention in the early mixed dentition. The aim was to report the
      occlusal findings at the baseline. The frequencies of mesial step, flush terminal
      plane, and distal step were 19.1%, 47.8%, and 33.1%, respectively. The canine
      relationship was Class I in 46.1%, Class II in 52.4%, and Class III in 1.5% of
      the sides examined. An asymmetrical canine relationship was found in 30.1% of the
      children, significantly more often on the right side than on the left (P <.001).
      Overjet ranged from -2 to +10 mm with a mean of 2.9 mm. Overbite ranged from -5
      to +8 mm with a mean of 2.8 mm. Excessive (> or =4 mm) overjet was found in 26.7%
      and overbite in 33.8% of the children; in 15.5% of the children, both variables
      were 4 mm or more. Anterior crowding was detected in the maxillary arch in 11.6%
      and in the mandibular arch in 38.9% of the children. Girls showed mandibular
      crowding more often than boys (P <.01). A posterior crossbite was found in 7.5%
      of the children, unilaterally in 6.4% and bilaterally in 1.1%. Scissors-bite was
      detected in 1.1% and an anterior crossbite in 2.2% of the children. The mean
      maximal opening was 40.3 mm. Joint sounds were registered in 5.2% of the
      children. The prevalence of malocclusion was between 67.7% and 92.7%, depending
      on the values of unacceptable parameters used for each occlusal characteristic.

PMID- 14666076
TI  - Cephalometric evaluation of the craniofacial complex in patients treated with an
      intraoral distraction osteogenesis device: a preliminary report.
AB  - The purpose of this pilot study was to evaluate cephalometrically the efficacy of
      an intraoral distraction osteogenesis device in treating patients with unilateral
      mandibular hypoplasia. Six patients with hemifacial microsomia underwent
      unilateral mandibular distraction. Posteroanterior and 45 degrees lateral oblique
      cephalograms were measured, and changes in maxillary width and height, occlusal
      height, ramus height, mandibular length, and chin position were quantified.
      Measurements were taken preoperatively and postoperatively at 7 time points (T1
      T7) over 2 years. Calculations for statistical significance were done to T6 for
      all patients and through T7 for 4 patients. The means and variances were
      calculated for the 6 cephalometric variables for each time point. The mean
      differences between treatment and control were calculated as well as analysis of
      variance. Mean differences between specific time periods were measured by
      pairwise comparison with significance determined at the 0.05 level of confidence.
      Statistical analysis was used for descriptive purposes only. The cephalometric
      data suggest that the intraoral distractor is as capable of lengthening
      hypoplastic mandibles as the initial extroral appliances. The bone lengthening
      appears stable, with the distracted side of the mandible maintaining a growth
      rate similar to the normal side. Immediately after distraction, transient
      improvements were noted in maxillary height, ramal height, and maxillary width.
      All patients demonstrated an immediate improvement in chin position toward the
      skeletal midline; however, after T4, menton appeared to be moving away from the
      midline over time.

PMID- 14666077
TI  - Prediction of maxillary canine impaction using sectors and angular measurement.
AB  - Maxillary canine impaction has an incidence of 1 in 100 in the general population
      and has been reported as much higher in an individual orthodontic practice.
      Because patients with canine impactions generally have longer treatment times,
      depending on the location of the impacted tooth, early identification of
      impaction is of critical interest to the orthodontist. Sector location and
      angulation of the unerupted tooth have been analyzed previously as predictors of
      canine eruption after deciduous extraction. Additionally, sector location has
      been studied as an indicator of eventual impaction, resulting in good predictive
      success. In this study, angulation of the unerupted tooth was measured from
      panoramic radiographs and added to sector location to see whether the combination
      of these factors could predict impaction more accurately than sector alone.
      Results verified earlier findings for sector: canines that become impacted will
      overlap the adjacent lateral incisor in 82% of cases. Logistic regression
      analysis also determined that once the canine overlaps the midline of the lateral
      incisor, there is a greater than 0.87 chance of impaction. Sector was found to be
      the better predictor of impaction, with angulation adding little supplementary
      predictive value.

PMID- 14666078
TI  - Asymmetry of the sphenoid bone and its suitability as a reference for analyzing
      craniofacial asymmetry.
AB  - The purposes of this study were to evaluate the asymmetry of the sphenoid bone
      and to determine its suitability as a reference for analyzing asymmetry of the
      skull. Thirty-seven dry skulls from India were divided into group A (n = 18),
      with a right-left length discrepancy of less than 2 mm for both the external
      acoustic meatus-frontozygomatic suture and external acoustic meatus-subspinale,
      and group B (n = 19), with a right-left length discrepancy of more than 2 mm for
      either of these 2 parameters. The skulls were then examined with regard to the
      percentage of asymmetry of the sphenoid bone, the angles between the cranial base
      and the facial axis, and the distance between reference surfaces of the sphenoid
      bone and facial landmarks by 3-dimensional measurement system. The following
      results were obtained: 1. Asymmetry of the sphenoid bone, while slight, was found
      in both groups. There were no significant differences between the 2 groups. 2.
      The cranial base and the facial axis did not form a right angle in group A, and
      there were no significant differences between the 2 groups. 3. The distances
      between reference surfaces of the sphenoid bone and the lower landmarks of the
      facial bone were greater than those of the upper landmarks. 4. The external
      acoustic meatus was the most suitable reference for analysis of craniofacial
      asymmetry.

PMID- 14666079
TI  - A new index for evaluating horizontal skeletal discrepancies and predicting
      treatment outcomes.
AB  - The cephalometric measurement known as Wits appraisal (AOBO) was studied to
      determine its importance in diagnosis, treatment, and prediction of treatment
      success. The Wits appraisal is used primarily to identify unreliable ANB values
      (those that do not accurately reflect the degree of horizontal jaw discrepancy,
      ie, those that differ greatly from the AOBO value). Therefore, differences
      between AOBO and ANB also were evaluated. Because neither measurement alone can
      assess jaw discrepancies with total accuracy, they were combined, plotted on a
      scattergram, and divided into equal zones to create a new index of horizontal
      skeletal discrepancies and treatment predictability. Pretreatment values
      correspond to treatment difficulty, and posttreatment values correspond to the
      effectiveness of treatment. Treatment time for each zone also was evaluated. We
      were able to draw several conclusions from this study. First, combining AOBO and
      ANB values results in a more accurate measurement of treatment difficulty. These
      combined values also can be used to predict both treatment time and the success
      of treatment for horizontal discrepancies. Second, the AOBO value predicts
      variations in treatment time at each ANB value. Finally, adding ANB and AOBO
      values and then dividing the total yields zones that represent statistically
      significant differences in treatment times and percentages of success. The zones
      also correlate with the difference between AOBO and ANB measurements.

PMID- 14666080
TI  - Craniofacial growth in untreated skeletal Class I subjects with low, average, and
      high MP-SN angles: a longitudinal study.
AB  - Sixty-eight (36 male and 32 female) untreated skeletal Class I subjects with low
      (< or = 27 degrees ), average (>27 degrees - <37 degrees ), and high (> or = 37
      degrees ) mandibular plane (MP-SN) angles were selected from the Bolton-Brush and
      Burlington Growth Studies. Cephalograms of each subject at ages 9 and 18 were
      traced, and 28 parameters were measured. The difference in each parameter from
      ages 9 to 18 was calculated, and comparisons were made between the groups with
      low, average, and high angles. Results showed that, for boys and girls at age 9,
      the low-angle groups exhibited significantly larger SNA angle, SNB angle, facial
      taper, PFH, PFH:AFH, and ramus height, and the high-angle groups showed
      significantly larger ANS-Me and gonial angle. From ages 9 to 18, all the male and
      female low-, average-, and high-angle groups showed an increase in SNA and SNB
      angles, and PFH:AFH, and a decrease in ANB angle, convexity (more flattened
      face), MP-SN angle, and gonial angle (mandibular forward rotation). The dental
      measurements showed few changes with growth in all groups. In terms of skeletal
      measurements from ages 9 to 18, similar growth changes were found between the
      sexes in most angular measurements, but males had larger values in linear
      measurements than females.

PMID- 14666081
TI  - Longitudinal changes in gingival condition in crowded and noncrowded dentitions
      subjected to fixed orthodontic treatment.
AB  - A previous study showed that initial crowding in the dentition was negatively
      correlated with gingival bleeding at the end of orthodontic treatment, whereas
      visible plaque on the labial surfaces had apparently no significant association
      with gingival health. The present study further examined the relationship between
      initial crowding and gingival health during fixed orthodontic treatment. A total
      of 220 patients were followed longitudinally during treatment. In this
      population, 2 groups, 1 consisting of 45 patients with severe crowding and 1
      consisting of 52 patients with no crowding, were examined more closely. The
      gingival bleeding index (GBI) was recorded at bonding, at 12, 24, and 48 weeks
      after bonding, and at debonding. At bonding, the GBI was the same in the 2
      groups. However, the GBI improved significantly from 12 weeks after bonding to
      debonding in the patients with crowded dentitions, whereas the patients with
      noncrowded dentitions showed no changes. Possible reasons for this difference
      were identified: to have the same GBI at bonding, despite the severe crowding,
      the patients in this group probably had better oral hygiene. Those with crowded
      dentitions had received more oral hygiene instruction within 2 years before
      bonding than those with noncrowded dentitions, according to the general
      practitioners' records. When the crowding was eliminated after approximately 3
      months, the conditions for cleaning the teeth were improved, and, accordingly,
      the patients' improved oral hygiene resulted in lowered GBI scores. One could
      also speculate that correcting the crowding during the first few months of
      treatment had a positive psychological effect, motivating the patients to use the
      skills in oral hygiene that they had adopted before treatment.

PMID- 14666082
TI  - Airborne particles produced during enamel cleanup after removal of orthodontic
      appliances.
AB  - Airborne particles can be produced during enamel cleanup after the removal of
      fixed orthodontic appliances. Particles with an aerodynamic diameter of less than
      2.5 microm, known as PM2.5, can reach the alveoli of the lungs. The aim of this
      experiment was to qualitatively determine whether such particles are produced
      during enamel cleanup at the end of orthodontic treatment. Particles were
      collected and examined under a scanning electron microscope. Aerodynamic
      diameters of the particles ranged from approximately 2 to 30 microm. X-ray
      analysis confirmed not only the presence of components of the adhesives being
      removed, but also tungsten from the bur and tooth enamel. In conclusion,
      inhalable particles can be produced during enamel cleanup at the completion of
      orthodontic treatment. Further investigation is required to determine the
      clinical significance of such particles, how their production can be minimized,
      and whether even smaller, fine or ultrafine, particles are produced.

PMID- 14666083
TI  - In vivo study on metal release from fixed orthodontic appliances and DNA damage
      in oral mucosa cells.
AB  - Interest in the amount of metal ion intake from dental alloys has grown. Fixed
      orthodontic appliances usually include brackets, bands, and archwires made of
      stainless steel, nickel-titanium, or nickel-cobalt alloys, and these can release
      metal ions. The purpose of this study was to investigate the biocompatibility in
      vivo of fixed orthodontic appliances, evaluating the presence of metal ions in
      oral mucosa cells, their cytotoxicity, and their possible genotoxic effects.
      Mucosa samples were collected by gentle brushing of the internal part of the
      right and left cheeks of 55 orthodontic patients and 30 control subjects who were
      not receiving orthodontic treatment. The cells were immediately prepared for cell
      viability and the comet assay. Nickel and cobalt cellular content was quantified
      by inductively coupled plasma mass spectrometry (ICP-MS). The results indicate
      that nickel and cobalt concentrations were 3.4-fold and 2.8-fold higher,
      respectively, in the patients than in the controls; cellular viability was
      significantly lower in the patients than in the controls, and there was a
      significant negative correlation with metal levels. The biologic effects,
      evaluated by alkaline comet assay, indicated that both metals induced DNA damage
      (more cells with comets and apoptotic cells). There were significant positive
      correlations between (1) cobalt levels and the number of comets and apoptotic
      cells, (2) nickel levels and number of comet cells, and (3) cobalt levels and
      comet tails. This study corroborates that nickel and cobalt released from fixed
      orthodontic appliances can induce DNA damage in oral mucosa cells.

PMID- 14666085
TI  - Jaw kinematics during mastication after unilateral fractures of the mandibular
      condylar process.
AB  - This study compared the mandibular kinematics during mastication of patients
      treated for unilateral fractures of the mandibular condylar process with those of
      control subjects. We used a Sirognathograph (Siemens, Bensheim, Germany) to
      record the chewing cycles of 81 male patients with unilateral condylar process
      fractures while they chewed a constant bolus unilaterally on the same side as the
      fracture and on the opposite side. Recordings were made at 6 weeks, 6 months, 1
      year, and 2 years after treatment. Similar chewing cycles were recorded for 15
      male controls (Class I dental and Class I skeletal occlusion) without fractures
      of the condylar process. The chewing cycles of both groups were analyzed with a
      custom computer program, and the duration, excursive ranges, and 3-dimensional
      cycle shape were compared at each time interval with multilevel linear modeling
      statistics. Fracture patients had significantly slower chewing cycles, with
      significantly less maximum excursion toward the working side during the closing
      phase and significantly greater excursion toward the balancing side during the
      opening phase than the controls. The opening pathway of the incisors showed
      greater differences between patients and controls than the closing pathways.
      Differences in chewing cycle shape persisted for up to 2 years, especially when
      chewing was on the side opposite the fracture. Unilateral condylar process
      fractures produce long-lasting changes in chewing cycle duration and chewing
      cycle shape of adults.

PMID- 14666086
TI  - Changes in mandibular incisor position in Class II Division 1 malocclusion
      treated with premolar extractions.
AB  - The aim of this study was to investigate the magnitude of mandibular incisor
      retraction to be expected during full fixed appliance mechanotherapy in Class II
      Division 1 malocclusions treated with premolar extractions when mandibular
      incisor retraction was not part of the treatment plan. The material consisted of
      pretreatment and posttreatment cephalometric films and dental casts of 70 Class
      II Division 1 malocclusion patients (33 males and 37 females) treated with the
      preadjusted edgewise appliances. The mandibular first premolars were extracted in
      31 subjects, and the mandibular second premolars were extracted in 39. The
      pretreatment factors that suggested a basis for the extraction choice in the
      mandibular arch in these patients were found to include the ratio between
      posterior and anterior facial heights, the maxillary-mandibular plane angle, and
      the residual space in the mandibular arch. The mandibular incisors were retracted
      in only 65% of the patients. On average, the mandibular incisors were retracted
      by 1.02 mm relative to the nasion-pogonion line; there was no significant
      difference between the 2 extraction groups. Multiple regression analysis showed
      that the change in the mandibular incisor position is significantly correlated
      with the residual space in the mandibular arch, the initial distance between the
      mandibular incisor and the nasion-pogonion line, maxillary-mandibular angle, and
      the duration of crown labial torque in the mandibular incisors. In combination,
      these 4 factors could explain 61% of the change in the mandibular incisor
      position.

PMID- 14666087
TI  - Periodontal status of orthodontic patients and the relationship between dental
      aesthetic index and community periodontal index of treatment need.
AB  - This prospective clinic-based study evaluated the pretreatment periodontal status
      of the orthodontic patients seen at the University College Hospital, Ibadan,
      Nigeria, and assessed the relationship between dental aesthetic index (DAI)
      scores and periodontal status according to community periodontal index of
      treatment needs (CPITN) scores. One hundred forty five patients-70 (48.3%) males
      and 75 (51.7%) females from 6 to 45 years (mean 15.8 +/- 7.5)-were seen. World
      Health Organization (WHO) guidelines were followed in the examination and
      reporting of the periodontal status, and DAI scores were assessed based on WHO
      guidelines. The chi-square test was used to determine the association between the
      DAI and the CPITN scores. Most patients were in the 6-15 (55.9%) or 16-25 (35.9%)
      age groups. Based on the WHO preferred cumulative calculations of treatment need
      (TN), 35.2% of the patients had TN 0, 64.9% had TN 1, 24.9% had TN 2, and only
      0.7% had TN 3. The relationship between DAI scores and periodontal treatment
      needs was not statistically significant (P >.05). Although many patients were yet
      to attain the WHO goal of no more than 1 sextant affected by bleeding or calculus
      at the age of 15, over one third had satisfactory periodontal health.

PMID- 14666088
TI  - An unusual case of fibrous dysplasia of the maxillary sinus.
AB  - Fibrous dysplasia of the maxillary sinus might initially become apparent because
      of facial asymmetry. It can be differentiated from other osseo-odontogenic
      dysplasias radiographically by its occupancy of the affected sinus and by its
      diffuse, ground-glass, radiopaque appearance; it can be further confirmed with
      histologic findings. It is normally self-limiting in growth and does not usually
      become malignant.

PMID- 14666089
TI  - Management of a hyperdivergent Class III malocclusion, maxillary midline
      diastema, and infected mandibular incisors in a young adult.
AB  - This is a case report of a 20-year-old woman with a hyperdivergent Class III
      malocclusion, infected mandibular incisors, maxillary midline diastema, and a
      mild tongue thrust. Extraction of the infected incisors and orthodontic treatment
      involving partial mesial movement of the remaining mandibular teeth produced a
      well-intercuspated Class III occlusion. After successful orthodontic treatment, a
      4-unit bridge with pontics for the mandibular central incisors completed the
      rehabilitation and met the functional, esthetic, and occlusal treatment goals.
      Occlusal stability of the treatment result has been excellent in the 3-year
      follow-up.

PMID- 14666090
TI  - Comparison of 3 bonded lingual appliances by auditive analysis and subjective
      assessment.
AB  - The aim of this prospective study was to compare for the first time the
      influences of lingual appliances of different dimensions on sound performance and
      oral comfort. The study group comprised 12 subjects (10 women, 2 men; mean age,
      33.96 years). Their sound production was recorded by means of a digital audio
      tape recorder before, 10 minutes after, and 24 hours after placement of the
      different appliances for semiobjective assessment by 3 blinded speech
      professionals. This was followed by supplementary subjective ratings of sound
      performance and oral comfort by the patients. All lingual appliances induced
      significant impairment in sound performance and oral comfort. However, they
      varied significantly with respect to the degree of impairment. The smaller the
      appliance, the less pronounced the impairments it induced. The smallest changes
      were induced by a bonded canine-to-canine retainer, followed by customized
      lingual brackets and prefabricated lingual brackets. By using lower-profile
      customized brackets, the orthodontist can significantly enhance patient comfort
      and significantly reduce impairments of sound performance in comparison with
      prefabricated brackets with larger dimensions. Before placing a lingual
      appliance, however, patients should be briefed on possible effects such as
      impaired sound production and decreased oral comfort.

PMID- 14666091
TI  - Litigation, legislation, and ethics. Handbooks or handcuffs.

PMID- 14666092
TI  - An inner compass.

PMID- 14666093
TI  - Lessons learned.

PMID- 14666094
TI  - Ten-fold expansion of a burn unit in mass casualty: how to recruit the nursing
      staff.
AB  - The first hours after a mass casualty event (MCE) are critical for the care of
      injured patients, especially for those with major burns. Burn patients are best
      treated in a specialized unit, however, transfer may not always be practical or
      possible. If transfer is not an option, hospitals need to find another solution
      to provide safe, effective, and efficient care. A critical element in providing
      burn care is to have a sufficient number of capable trained nurses. The Rambam
      Medical Center in Haifa, Israel evaluated past experience and has developed an
      innovative and comprehensive plan to provide treatment for a large influx of burn
      patients. The plan allows the 15-bed burn unit to expand and treat up to 136 burn
      victims, uses supplementary personnel, and allocates hospital beds and equipment
      as needed. This article describes the educational program that is used to prepare
      supplemental nurses.

PMID- 14666095
TI  - Earthquakes in El Salvador: a descriptive study of health concerns in a rural
      community and the clinical implications, part I.
AB  - INTRODUCTION: This is the first article in a series that evaluates the health
      concerns of people living in a Salvadoran rural community after major
      earthquakes. Part I reviews the background, methods, and results of post
      earthquake conditions with regards to healthcare, access to healthcare, housing,
      food, water and sanitation. Part II reviews the implications of these results and
      recommendations for improvements within the community. Part III investigates the
      psychosocial and mental health consequences of the earthquakes and provides
      suggestions for improved mental health awareness, assessment, and intervention.
      BACKGROUND: El Salvador experienced 2 major earthquakes in January and February
      2001. This study evaluates the effects of the earthquakes on the health practices
      in the rural town of San Sebastian. METHODS: The research was conducted with use
      of a convenience sample survey of subjects affected by the earthquakes. The
      sample included 594 people within 100 households. The 32-question survey assessed
      post-earthquake conditions in the areas of health care and access to care,
      housing, food and water, and sanitation. RESULTS: Communicable diseases affected
      a number of family members. After the earthquakes, 38% of households reported new
      injuries, and 79% reported acute exacerbations of chronic illness. Rural
      inhabitants were 30% more likely to have an uninhabitable home than were urban
      inhabitants. Concerns included safe housing, water purification, and waste
      elimination. CONCLUSION: The findings indicate a need for greater public health
      awareness and community action to adapt living conditions after a disaster and
      prevent the spread of communicable disease.

PMID- 14666096
TI  - Considerations for chemical decontamination shelters.

PMID- 14666097
TI  - Lessons learned: the "pale horse" bioterrorism response exercise.
AB  - The city of San Antonio, Texas, and the Fort Sam Houston Army Post conducted a
      bioterrorism response exercise to test the command infrastructure in a large
      tabletop exercise. A number of local, state, and federal agencies participated in
      the exercise. The scenario, program format, and multiple lessons learned from
      this experience are described. Needs for additional services, planning, and legal
      issues are identified.

PMID- 14666098
TI  - Emergency preparedness for an extended utility outage.

PMID- 14666112
TI  - The evolution of molecular markers--just a matter of fashion?

PMID- 14666113
TI  - Therapeutic vaccination for chronic diseases: a new class of drugs in sight.

PMID- 14666114
TI  - Demonstration of the efficacy and safety of a novel substance P (NK1) receptor
      antagonist in major depression.
AB  - The efficacy and safety of a selective NK(1) antagonist, L-759274, was
      investigated in outpatients with diagnosis of major depressive disorder with
      melancholic features, following evidence obtained with the novel compound
      aprepitant that Substance P (NK(1)) antagonists may provide a unique mechanism of
      antidepressant activity. A randomized, double-blind placebo-controlled study was
      carried out. Patients, male or female, aged 18-60, scoring >/=25 points on total
      of first 17 items of 21-item Hamilton Depression Scale (HAMD), and scoring >/=4
      (moderately ill) on Clinical Global Impressions-Severity Scale were randomized to
      oral L-759274 40 mg daily (n=66) or placebo (n=62) for 6 weeks. For patients
      receiving L-759274, improvement (mean decrease from baseline) in HAMD-17 total
      score was 10.7 points, compared with a mean 7.8 point improvement in patients
      receiving placebo (p<0.009). Mean scores for item 1 of HAMD-17 (depressed mood)
      also improved to a greater extent in the active group compared with the placebo
      group (0.3 points, p<0.058). Compared with placebo, mean scores on Clinical
      Global Impressions-Improvement Scale improved significantly by the end of the
      trial (p=0.009). L-759274 was generally safe and well-tolerated. The incidence of
      sexual side effects was on par with that observed in patients receiving placebo,
      and the incidences of gastrointestinal effects were low. Antidepressant actions
      have now been observed with two different highly selective NK(1) antagonists
      (aprepitant and L-759274). NK(1) antagonism is a replicated and generally well
      tolerated antidepressant mechanism.

PMID- 14666115
TI  - Nicotine-induced dopamine release in primates measured with [11C]raclopride PET.
AB  - Nicotine-induced dopamine (DA) release constitutes a pharmacological probe of the
      DA system that has potential use in patients with schizophrenia, who have
      abnormally elevated DA release after amphetamine administration and possibly
      abnormalities in nicotinic signaling. We performed positron emission tomography
      studies in five rhesus monkeys that received i.v. nicotine doses ranging from
      0.01 to 0.06 mg/kg. [(11)C]raclopride was administered with either a bolus plus
      constant infusion or with paired bolus injections. The dynamics of D-2-binding
      potential (BP) after nicotine administration were studied and compared to
      amphetamine. Nicotine caused a significant albeit small reduction (5%, p<0.03) in
      BP, regardless of methodology of tracer administration. This effect disappeared
      2.5 h after nicotine administration. Amphetamine caused much larger and prolonged
      displacement of [(11)C]raclopride as compared to nicotine. There was no
      correlation between changes in BP and nicotine dose or plasma level. Regional
      differences in the nicotine effect within the basal ganglia were not found. Our
      data are consistent with the increase in DA detected with microdialysis in
      animals after acute nicotine administration, however, a larger effect size would
      be desirable to attempt studies comparing human smokers with and without
      schizophrenia.

PMID- 14666116
TI  - GABA(A) and opioid receptors of the central nucleus of the amygdala selectively
      regulate ethanol-maintained behaviors.
AB  - The present study tested the hypothesis that GABA(A) and opioid receptors within
      the central nucleus of the amygdala (CeA) regulate ethanol (EtOH), but not
      sucrose-maintained responding. To accomplish this, betaCCt, a mixed
      benzodiazepine (BDZ) agonist-antagonist with binding selectivity at the alpha1
      subunit-containing GABA(A) receptor, and the nonselective opioid antagonist,
      naltrexone, were bilaterally infused directly into the CeA of alcohol-preferring
      rats. The results demonstrated that in HAD-1 and P rat lines, betaCCt (5-60
      microg) reduced EtOH-maintained responding by 56-89% of control levels. On day 2,
      betaCCt (10-40 microg) continued to suppress EtOH maintained responding in HAD-1
      rats by as much as 60-85% of control levels. Similarly, naltrexone (0.5-30
      microg) reduced EtOH-maintained responding by 56-75% of control levels in P rats.
      betaCCt and naltrexone exhibited neuroanatomical and reinforcer specificity
      within the CeA. Specifically, no effects on EtOH-maintained responding were
      observed following infusion into the caudate putamen (CPu), a locus several
      millimeters dorsal to the CeA. Additionally, responding maintained by sucrose,
      when presented concurrently with ethanol (EtOH) or presented alone, was not
      altered by betaCCt. Naltrexone reduced sucrose-maintained responding only under
      the 5 microg dose condition when sucrose was presented alone, however, it did not
      alter sucrose responding when given concurrently with EtOH. These results support
      the hypothesis that GABA(A) and opioid receptors within the CeA can selectively
      regulate EtOH-maintained responding. The CeA may represent a novel target site in
      the development of prototypical GABA(A) and opioidergic receptor ligands, which
      selectively reduce alcohol abuse in humans.

PMID- 14666117
TI  - Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor
      and panic disorder.
AB  - Data from clinical and behavioral pharmacological studies have implicated
      adenosine in anxiety behaviors, while genetic studies have suggested that
      adenosine receptors may be associated with panic disorder. We have undertaken an
      analysis of several DNA sequence variations in the adenosine 2A receptor
      (ADORA2A) in a large sample of panic disorder pedigrees. Individuals from 70
      panic disorder pedigrees, and 83 child-parent 'trios', were genotyped at five
      single-nucleotide polymorphisms (SNPs) in and near the ADORA2A gene and were
      analyzed for genetic linkage and association. Linkage analysis revealed elevated
      LOD scores for a silent substitution (1083C/T, SNP-4) in the second coding exon.
      This SNP has been previously reported to be associated with panic disorder. We
      observed a maximal heterogeneity LOD score of 2.98 (theta=0) under a recessive
      genetic model and narrow diagnostic model. Other SNPs showed no evidence for
      linkage. Association tests were not significant for any of the five ADORA2A SNPs.
      When SNP haplotypes were assessed in the triads with TRANSMIT, one 3-marker
      haplotype (SNPs 1, 4, 5) was nominally significantly associated with panic
      disorder (p=0.029). Pairwise estimations of linkage disequilibrium between the
      SNPs showed strong patterns of linkage disequilibrium across the ADORA2A locus.
      Analyses carried out by broadening the panic disorder phenotype to include
      agoraphobia continued to support linkage to ADORA2A. Our findings provide
      evidence for a susceptibility locus for panic disorder, and possibly including
      agoraphobia, either within the ADORA2A gene or in a nearby region of chromosome
      22, and serves as the first successful candidate gene replication study in panic
      disorder.

PMID- 14666118
TI  - Injection of the 5-HT2C receptor agonist Ro60-0175 into the ventral tegmental
      area reduces cocaine-induced locomotor activity and cocaine self-administration.
AB  - Previously, we have shown that systemic administration of the 5-HT(2C) receptor
      agonist Ro60-0175 reduces cocaine-induced locomotor activity and cocaine self
      administration. Ro60-0175 also alters the activity of midbrain dopamine (DA)
      neurons of the ventral tegmental area (VTA), a region where 5-HT(2C) receptors
      are expressed. The present experiments investigated whether microinjections of
      Ro60-0175 into the VTA would alter the locomotor stimulant effect of cocaine and
      cocaine self-administration. In the tests for locomotor activity injection of 3
      and 10, but not 1 microg, Ro60-0175 into the VTA reduced the locomotor
      stimulation resulting from injection of 10 mg/kg cocaine. In tests of cocaine
      self-administration, rats were trained to lever press for intravenous infusions
      of 0.25 mg cocaine delivered on either a fixed ratio 5 (FR5) or a progressive
      ratio schedule. Intra-VTA injection of Ro60-0175 at doses of 3 and 10 microg
      reduced responding for cocaine on both schedules without significantly altering
      the latency to initiate responding or the rate of responding. A subsequent
      experiment determined that the suppressant effect of intra-VTA Ro60-0175 (3
      microg) on responding for cocaine was prevented by pretreatment with the
      selective 5-HT(2C) receptor antagonist SB242,084 (0.5 mg/kg). In a final
      experiment, intra-VTA injection of Ro60-0175 reduced responding for food
      reinforcement on the same progressive ratio schedule as used for cocaine self
      administration. These results demonstrate that stimulation of 5-HT(2C) receptors
      in the VTA is sufficient to attenuate the stimulant and reinforcing effects of
      cocaine. These effects complement electrophysiological and neurochemical
      findings, and indicate that 5-HT(2C) receptors localized within the VTA modulate
      the activity of mesolimbic DA neurons.

PMID- 14666119
TI  - In the amygdala anxiolytic action of mGlu5 receptors antagonist MPEP involves
      neuropeptide Y but not GABAA signaling.
AB  - Several lines of evidence indicate that inhibition of the metabotropic glutamate
      (mGlu) receptor 5 produces anxiolytic-like effects in rodents. Peptide
      neurotransmitter neuropeptide Y (NPY) produces an anxiolytic effect in rats after
      intraventricular or intra-amygdalar administration. Many classes of anxiolytic
      drugs exert their effect through the GABA-benzodiazepine (BZD) receptor complex.
      Therefore, in the present study we have investigated whether the anxiolytic
      action of MPEP (2-methyl-6-(phenylethynyl)pyridyne), an mGlu5 receptor
      antagonist, is mediated by a mechanism involving either the GABA-BZD receptor
      complex or NPY receptor. In the behavioral studies, the anxiolytic activity of
      MPEP (10 mg/kg, i.p.) was examined using plus-maze test. The BZD antagonist
      flumazenil (10 mg/kg, i.p.) was given to one group of rats and Y1 receptor
      antagonist BIBO 3304 (((R)-N-[[4-(aminocarbonylaminomethyl) phenyl] methyl]-N2
      (diphenylacetyl)-argininamide trifluoroacetate)3304) (200 pmol/site, intra
      amygdala) to the other. It was found that anxiolytic effects of MPEP were not
      changed by flumazenil, but were abolished by BIBO 3304. Immunohistochemical
      studies showed a high density of mGlu5 receptor immunoreactivity (IR) in the
      amygdala. The effect of MPEP on NPY expression in the amygdala was studied using
      immunohistochemistry (IH) and radioimmunoassay (RIA). Both methods showed a
      diminution of NPY IR expression, to about 43% (IH) or 81% (RIA) of the control
      level after multiple administrations, but we observed an increase up to 148% of
      the control after single MPEP administration. These effects may suggest a release
      of NPY from nerve terminals after MPEP administration. Our results indicate that
      the anxiolytic action of MPEP is conveyed through NPY neurons with the
      involvement of Y1 receptors in the amygdala and that BZD receptors do not
      significantly contribute to these effects.

PMID- 14666120
TI  - Apomorphine-induced prepulse inhibition disruption is associated with a
      paradoxical enhancement of prepulse stimulus reactivity.
AB  - Prepulse inhibition (PPI) refers to the reduction in startle reaction to a
      startle-eliciting stimulus when it is shortly preceded by a subthreshold prepulse
      stimulus. PPI has been extensively employed as an assay for sensorimotor gating,
      and its disruption has been characterized in specific disease conditions,
      including schizophrenia. In animals, dopamine agonists disrupt PPI, and this
      disruption can be antagonized by antipsychotic drug treatment. The present study
      extended these fundamental findings to C57BL6 mice, and further evaluated the
      subjects' reaction to the prepulse stimulus alone in relation to the expression
      of PPI. Not only did apomorphine (2.0 mg/kg, intraperitoneal (i.p.)) attenuate
      PPI but it also enhanced reactivity to the prepulse stimulus. The dual effects of
      apomorphine appear paradoxical in view of the positive correlation, detectable in
      both the control and apomorphine groups, between prepulse reactivity and PPI
      magnitude. The present findings contradict the hypothesis that apomorphine
      disrupts PPI via reduced detectability or perception of the prepulse, and we
      further propose that enhanced distractibility may provide a parsimonious account
      for the dual effects of apomorphine. Moreover, haloperidol pretreatment (0.4
      mg/kg, i.p.) fully antagonized the effects of apomorphine upon prepulse
      reactivity as well as on PPI. The present results add to our understanding of the
      relevance and applicability of the PPI paradigm in modeling schizophrenia-like
      symptoms in animals.

PMID- 14666121
TI  - Effect of topiramate on glucocorticoid receptor mediated action.
AB  - This study examined the effects of topiramate (TPM) on glucocorticoid receptors
      (GRs) in mononuclear leukocytes of nine men and four women with chronic and
      recurring post-traumatic stress disorder (PTSD) and a group of comparison
      subjects (nine men, four women). A measure of 60 ml of blood was withdrawn by
      venipuncture at 0800 and mononuclear leukocytes were isolated. The cells were
      incubated with a series of concentrations of dexamethasone (DEX) without or with
      50 micromol/l of TPM to evaluate the effects of DEX to inhibit lysozyme activity
      and the effect of TPM on it. ANCOVA compared the IC(50) for lysozyme inhibition
      under conditions of DEX only and TPM+DEX. TPM affected lysozyme IC(50) in the
      direction of increasing the sensitivity of the receptor in the sample as a whole.
      This effect was more pronounced in the mononuclear leukocytes from participants
      in the PTSD group, particularly in cells from subjects whose pretreatment
      lysozyme IC(50) was relatively higher (eg, reflecting decreased glucococorticoid
      receptor responsiveness), compared to the rest of the sample. In conclusion,
      further investigation of the actions of TPM on GR and other neuroendocrine
      systems may prove useful in understanding some of the other established clinical
      effects of this agent.

PMID- 14666122
TI  - Physiological predictors of reproductive outcome and mother-infant behaviors in
      captive rhesus macaque females (Macaca mulatta).
AB  - Previous research has shown that offspring of females with low cerebrospinal
      fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations are less likely to
      survive the first year of life than are offspring of females with high CSF 5-HIAA
      concentrations. In addition, studies of free-ranging rhesus macaque males have
      suggested that individuals with low CSF 5-HIAA concentrations suffer reduced
      reproductive success relative to their high serotonin counterparts. We examined
      CSF concentrations of the monoamine metabolites 5-HIAA and homovanillic acid
      (HVA), and plasma cortisol concentrations as predictors of first-time adult
      reproductive potential, maternal behavior, and overall social interactions in two
      groups of captive female rhesus macaques and their first offspring. Repeated CSF
      and blood samples were obtained from adult females in two social groups, and
      focal observations were performed for both new mothers and infants during the
      first month following parturition. We found that the reproductively aged
      nulliparous females who failed to give birth to their first offspring showed
      significantly lower CSF 5-HIAA concentrations than those females who gave birth.
      Among those females that gave birth to offspring, females with low CSF 5-HIAA
      concentrations and females with high plasma cortisol concentrations were overly
      protective and restrictive with their infants. CSF HVA concentration was not
      associated with reproductive output, social behavior, aggression, or mother
      infant interactions in this sample of rhesus macaque females. We conclude that
      low CNS serotonin activity and high stress, measured by high plasma cortisol, are
      correlated with reduced reproductive success and patterns of high maternal
      restrictiveness in young adult female rhesus macaques.

PMID- 14666123
TI  - Behavioral and neurochemical vulnerability during adolescence in mice: studies
      with nicotine.
AB  - People are very likely to start psychoactive drug use during adolescence, an
      earlier onset being associated with a higher risk of developing addiction later
      in life. In experiment I, Pre- (postnatal day (pnd) 23-35), Mid- (pnd 36-48), or
      Post- (pnd 49-61) adolescent mice underwent a restricted-drinking period (2 h/day
      for 12 days), one bottle containing water and the other containing nicotine (10
      mg/l) or water. After this period, Mid-adolescents showed prominent exploration
      and reduced anxiety in the plus-maze. This ontogenetic profile was dampened by
      nicotine consumption. After 2 months, these mice were tested in a novel
      environment (30 min/day for 3 days). Locomotor-habituation profiles were
      specifically disrupted by nicotine consumption during Mid-adolescence, suggesting
      this age as a critical period. In experiment II, Mid-adolescent (pnd 35-44) and
      adult (pnd > 70) mice were pretreated with nicotine (0, 0.03, 0.10, 0.30
      mg/kg/day for 10 days). Acute nicotine administration had opposite effects on
      anxiety in adolescents and adults. At 2 months after pretreatment, we measured
      levels of AMPA GluR2/3 subunits, thought to be involved in the control of
      addictive behaviors. Nicotine exposure during Mid-adolescence dose-dependently
      downregulated these subunits in the striatum and hippocampus, but comparable
      exposure during adulthood had either opposite or no effects. NMDA NR2A/B subunits
      were affected by nicotine, but without age-related differences. The present data
      identified a nicotine-vulnerable age window, characterized by long-term
      disruption of locomotor habituation and downregulation of AMPA receptors. These
      findings support neurobiological vulnerability to drugs in adolescent humans.

PMID- 14666124
TI  - Kin-biased distribution in brown trout: an effect of redd location or kin
      recognition?
AB  - A wide range of animals have been reported to show kin-biased behaviours, such as
      reduced aggressiveness and increased food sharing among relatives. However, less
      is known about whether wild animals also associate with relatives under natural
      conditions, which is a prerequisite to facilitate kin-biased behaviours and hence
      kin selection. We tested, by means of microsatellite polymorphism, correlations
      between pair-wise relatedness and pair-wise metric distance in wild brown trout
      (Salmo trutta L.) under natural conditions in two streams. Our data show that
      young-of-the-year as well as older trout found close together also had a higher
      genetic relatedness in one of the two streams, whereas no relationship was found
      in the other stream. Very few half and full siblings were found in the second
      stream and under these conditions it is unlikely that kin-biased behaviours will
      receive positive selection. We discuss the underlying mechanisms for the observed
      structure and we specifically address the issue of whether the grouping of
      related individuals could reflect dispersal from the same spawning redds, or if
      it reflects active association with relatives, possibly conferring kin-selected
      advantages.

PMID- 14666125
TI  - Revisiting the role of introgression vs shared ancestral polymorphisms as key
      processes shaping genetic diversity in the recently separated sibling species of
      the Anopheles gambiae complex.
AB  - The role of interspecific hybridisation in the evolution of pest species is
      poorly understood. In mosquito disease vectors this is of particular importance
      due to the evolution of insecticide resistance and the proposed release of
      transgenic strains that are refractory to the malaria parasite. In this study, we
      apply population genetic methods in a novel manner to determine whether
      mitochondrial DNA sequences have introgressed between the closely related African
      malaria vectors Anopheles gambiae and A. arabiensis. Our results suggest that
      speciation was geologically recent and ancestral haplotypes at the ND5 locus are
      retained in both species. In addition, comparing haplotype frequencies in
      allopatric and sympatric populations, suggest locale specific unidirectional
      introgression of mitochondria from A. arabiensis into A. gambiae.

PMID- 14666126
TI  - Geographic origin and taxonomic status of the invasive Privet, Ligustrum robustum
      (Oleaceae), in the Mascarene Islands, determined by chloroplast DNA and RAPDs.
AB  - Information concerning the area of origin, genetic diversity and possible
      acquisition of germplasm through hybridisation is fundamental to understanding
      the evolution, ecology and possible control measures for an introduced invasive
      plant species. Among the most damaging of alien plants that are invading and
      degrading native vegetation in the Mascarene Islands of the Indian Ocean is the
      Tree Privet, Ligustrum robustum. Exact information about the geographic source of
      introduced material of this species is lacking, in part because Ligustrum is a
      taxonomically difficult genus. Native material of L. robustum ssp. walkeri from
      Sri Lanka, L. robustum ssp. robustum from northeastern India, and the closely
      related L. perrottetii from southern India was compared with introduced material
      from La Reunion and Mauritius using chloroplast DNA RFLP markers and random
      amplified polymorphic DNA (RAPDs). Sri Lankan and introduced material was
      monomorphic for the same cpDNA haplotype that was absent from south and northeast
      Indian Ligustrum. Sri Lankan and introduced material was also clearly
      distinguished from Indian Ligustrum by RAPDs. It was concluded that material
      introduced and established in the Mascarene Islands is derived from the Sri
      Lankan subspecies L. robustum ssp. walkeri. No geographic structuring of genetic
      variation within Sri Lanka was detected for this taxon, so the location(s) within
      Sri Lanka from which introduced material is derived could not be pinpointed.
      RAPDs indicate that L. robustum ssp. walkeri in Sri Lanka is more similar to
      south Indian L. perrottetii than to northeast Indian L. robustum ssp. robustum.
      Moreover, RAPDs showed that introduced material in La Reunion has undergone
      little or no loss of genetic diversity since introduction. However, there was no
      evidence that it is introgressed with germplasm from two other alien Ligustrum
      species present on La Reunion.

PMID- 14666127
TI  - Patterns of population structure in maize landraces from the Central Valleys of
      Oaxaca in Mexico.
AB  - Assessing the impact of farmer management of maize landraces in the Central
      Valleys of Oaxaca, Mexico is crucial to an understanding of maize evolution, as
      it was first domesticated there. In this paper, we report on the impact of
      traditional farmer management of maize populations in this region in structuring
      molecular diversity and on the population dynamics of maize landraces. These
      populations, from a sample of local landraces cultivated by farmers in six
      villages, show little among-population differentiation (Fst=0.011). Most
      surprisingly, there is no isolation by distance and small among-village
      differentiation (Fst=0.003). For an outbreeding plant such as maize, one would
      expect populations to fit Hardy-Weinberg equilibrium, but significant homozygote
      excess (Fis=0.13) was found. This homozygote excess shows remarkable
      interpopulation and interlocus differences. We show that this pattern is related
      to variation in the mean anthesis-silking interval as well as to the flowering
      range or heterogeneity in flowering of a given population. A short anthesis
      silking interval and high level of heterogeneity in flowering precocity will
      favor assortative mating. This leads to a locus-dependent population substructure
      giving an unusual case of Wahlund effect and inbreeding while high levels of seed
      exchange among farmers prevent population differentiation at both village and
      regional levels.

PMID- 14666128
TI  - Population structure and strong divergent selection shape phenotypic
      diversification in maize landraces.
AB  - To conserve the long-term selection potential of maize, it is necessary to
      investigate past and present evolutionary processes that have shaped quantitative
      trait variation. Understanding the dynamics of quantitative trait evolution is
      crucial to future crop breeding. We characterized population differentiation of
      maize landraces from the State of Oaxaca, Mexico for quantitative traits and
      molecular markers. Qst values were much higher than Fst values obtained for
      molecular markers. While low values of Fst (0.011 within-village and 0.003 among
      villages) suggest that considerable gene flow occurred among the studied
      populations, high levels of population differentiation for quantitative traits
      were observed (ie an among-village Qst value of 0.535 for kernel weight). Our
      results suggest that although quantitative traits appear to be under strong
      divergent selection, a considerable amount of gene flow occurs among populations.
      Furthermore, we characterized nonproportional changes in the G matrix structure
      both within and among villages that are consequences of farmer selection. As a
      consequence of these differences in the G matrix structure, the response to
      multivariate selection will be different from one population to another. Large
      changes in the G matrix structure could indicate that farmers select for genes of
      major and pleiotropic effect. Farmers' decision and selection strategies have a
      great impact on phenotypic diversification in maize landraces.

PMID- 14666129
TI  - Increased heterozygosity and allele variants are seen in Texel compared to
      Suffolk sheep.
AB  - In this study, the Suffolk and Texel sheep breeds were compared for
      microsatellite marker heterozygosity throughout seven chromosomal regions in the
      sheep genome. A total of 623 Texel animals and 489 Suffolk animals in five and
      three half-sib families, respectively, were genotyped for microsatellite markers
      across the seven different chromosomes. Using the observed allele frequencies,
      the expected levels of heterozygosity were calculated for each family. The
      expected levels of heterozygosity did not significantly differ between the breeds
      across all regions studied. However, levels of expected heterozygosity were 32%
      higher in Texel animals on chromosome 4 due to a region of increased
      heterozygosity between BMS648 and BM3212. The number of allelic variants
      significantly differed between the breeds, solely due to a region of increased
      number of alleles on chromosome 20. This region of higher numbers of allele
      variants in the Texel breed extended from the MHC to c. 15 cM distal to the MHC
      region incorporating markers OMHC1, CSRD226, TGLA387 and BM1818, which had 3.30,
      7.02, 3.09 and 6.75 more alleles in Texel than in Suffolk animals, respectively.
      No difference was observed in the variance of allele frequency between the two
      breeds. It is proposed that previous selective sweeps may have reduced numbers of
      alleles and levels of heterozygosity in the Suffolk breed.

PMID- 14666130
TI  - Contrasting population structures in two sympatric anurans: implications for
      species conservation.
AB  - A general prediction of the neutral theory of evolution is that genetic diversity
      should correlate positively with effective population size. We show here that
      diversity across eight microsatellite loci was consistently and substantially
      lower in one common amphibian (Bufo bufo) than in another with similar life
      history traits (Rana temporaria) despite B. bufo having the larger breeding
      assemblage sizes. However, B. bufo breeding assemblages were much more highly
      differentiated than those of R. temporaria according to both Fst and Rst
      estimators. These differences occurred in shared habitats across identical
      geographical distances. The patterns of genetic diversity and differentiation
      detected in these two species were probably a consequence of high gene flow in R.
      temporaria but much lower gene flow among the larger but more dispersed B. bufo
      assemblages. These observations highlight the difficulty of defining the
      boundaries of wild populations, and show how two broadly similar species can
      exhibit very different population dynamics.

PMID- 14666131
TI  - Single-locus complementary sex determination in the inbreeding wasp Euodynerus
      foraminatus Saussure (Hymenoptera: Vespidae).
AB  - The Hymenoptera have arrhenotokous haplodiploidy in which males normally develop
      from unfertilized eggs and are haploid, while females develop from fertilized
      eggs and are diploid. Multiple sex determination systems are known to underlie
      haplodiploidy, and the best understood is single-locus complementary sex
      determination (sl-CSD) in which sex is determined at a single polymorphic locus.
      Individuals heterozygous at the sex locus develop as females; individuals that
      are hemizygous (haploid) or homozygous (diploid) at the sex locus develop as
      males. sl-CSD can be detected with inbreeding experiments that produce diploid
      males in predictable proportions as well as sex ratio shifts due to diploid male
      production. This sex determination system is considered incompatible with
      inbreeding because the ensuing increase in homozygosity increases the production
      of diploid males that are inviable or infertile, imposing a high cost on matings
      between close relatives. However, in the solitary hunting wasp Euodynerus
      foraminatus, a species suspected of having sl-CSD, inbreeding may be common due
      to a high incidence of sibling matings at natal nests. In laboratory crosses with
      E. foraminatus, we find that sex ratios and diploid male production (detected as
      microsatellite heterozygosity) are consistent with sl-CSD, but not with other sex
      determination systems. This is the first documented example of sl-CSD in a
      hymenopteran with an apparent natural history of inbreeding, and thus presents a
      paradox for our understanding of hymenopteran genetics.

PMID- 14666132
TI  - Two whitebacked planthopper resistance genes in rice share the same loci with
      those for brown planthopper resistance.
AB  - The whitebacked planthopper (WBPH), Sogatella furcifera, and brown planthopper
      (BPH) Nilaparvata lugens Stal are important sucking insects of rice (Oryza sativa
      L.) crops throughout the world. Rice 'B5', which has derived its resistance genes
      from the wild rice O. officinalis Wall ex Watt, is a line that is highly
      resistant to both WBPH and BPH. Previously, two resistance genes against BPH,
      Qbp1, and Qbp2 in 'B5' had been mapped onto chromosome 3 and chromosome 4,
      respectively. In this study, we employed a mapping population composed of 187
      recombinant inbred lines (RILs), produced from a cross between 'B5' and
      susceptible variety 'Minghui63', to locate the WBPH and BPH resistance genes. A
      RFLP survey of the bulked extremes from the RIL population identified two genomic
      regions, one on chromosome 3 and the other on chromosome 4, likely containing the
      resistance genes to planthoppers. QTL analysis of the RILs further confirmed that
      two WBPH resistance genes were mapped on the same loci as Qbp1 and Qbp2, using a
      linkage map with 242 molecular markers distributed on 12 rice chromosomes. Of the
      two WBPH resistance genes, one designated Wbph7(t) was located within a 1.1-cM
      region between R1925 and G1318 on chromosome 3, the other designated Wbph8(t) was
      within a 0.3-cM region flanked by R288 and S11182 on chromosome 4. A two-way
      analysis of variance showed that two loci acted independently with each other in
      determining WBPH resistance. The results have significant implications in
      studying the interactions between sucking insects and plants and in breeding
      programs of resistance to rice planthoppers.

PMID- 14666133
TI  - Population genetic structure in European populations of Spiranthes romanzoffiana
      set in the context of other genetic studies on orchids.
AB  - Spiranthes romanzoffiana Cham. is restricted in Europe to the British Isles,
      where it is recognised as a conservation priority species due to frequent
      extirpation of populations along with no evidence of seed set; vegetative
      reproduction has been invoked as the sole means of perpetuation and dispersal. To
      investigate the reproductive ecology of this species, 17 populations have been
      sampled for chloroplast microsatellites and amplified fragment length
      polymorphisms (AFLPs). These markers revealed a previously unsuspected genetic
      geographic split in the species, which correlates with differences in patterns of
      within-population variation. Northern populations were fixed for one chloroplast
      haplotype but showed high levels of AFLP genotypic diversity consistent with
      sexual reproduction (proportion of genotypes distinguishable, PD = 0.98). More
      southerly populations showed fixed differences from the northern populations in
      their chloroplast haplotype and for 10 AFLP markers. They harboured only 12
      unique multilocus genotypes among 113 individuals from six populations (PD =
      0.11). These genotypes differed mostly by single bands, and none by more than
      4/138 loci, with identical multilocus genotypes occurring in widely separated
      populations. This uniformity in southern populations is consistent with
      agamospermous or autogamous reproduction, and/or an extreme population
      bottleneck. Finally, the observed patterns of population differentiation in S.
      romanzoffiana are compared with other studies of orchids, revealing a wide range
      of values that belie recent contrasting published generalisations that claim that
      orchids show either higher, or lower, levels of population differentiation than
      other plant families.

PMID- 14666134
TI  - A highly divergent mitochondrial DNA lineage of Microtus agrestis in southern
      Europe.
AB  - The Mediterranean peninsulas constitute important areas for endemism and
      intraspecific variation, and are likely places for cryptic biodiversity. We
      assessed the phylogeographic pattern of field voles (Microtus agrestis) in
      southern and central Europe by sequence analysis of a 385-bp fragment of the
      mitochondrial cytochrome b gene in 74 specimens from 44 localities. The majority
      of samples consisted of skulls collected from owl pellets. The data revealed a
      highly distinct cytochrome b lineage in an area ranging from Portugal to Hungary.
      This southern field vole phylogroup differed by a sequence divergence of 5.6-7.1%
      from the remaining haplotypes, a level of divergence comparable to that found
      between known Microtus sibling species. However, this ancient phylogeographic
      break that dates back many glacial cycles has not been recognised previously by
      either morphology or karyotype. The southern cytochrome b lineage was further
      divided into two well-defined sublineages that appear to have derived from
      different glacial refugia in the Iberian Peninsula.

PMID- 14666135
TI  - The influence of floral display size on selfing rates in Mimulus ringens.
AB  - Pollinators often visit several flowers in sequence on plants with large floral
      displays. This foraging pattern is expected to influence the rate of self
      fertilization in self-compatible taxa. To quantify the effects of daily floral
      display on pollinator movements and selfing, we experimentally manipulated flower
      number in four replicate (cloned) arrays of Mimulus ringens (Scrophulariaceae),
      each consisting of genets with unique combinations of homozygous marker
      genotypes. Four display classes (two, four, eight and 16 flowers) were present in
      each array. Pollinator visitation rate per flower and seed set per fruit were
      unaffected by display. However, flower number strongly influenced the frequency
      of within-plant pollinator movements, which increased from 13.8% of probes on two
      flower displays to 77.6% of probes on 16-flower displays. The proportion of
      within-plant movements was significantly correlated with selfing (r = 0.993). The
      increase from 22.9% selfing on two-flower displays to 37.3% selfing on 16-flower
      displays reflects changes in the extent of geitonogamous self-pollination. We
      estimate that approximately half of all selfing on 16-flower displays resulted
      from geitonogamy. Selfing also varied dramatically among fruits within display
      classes. Nested ANOVA indicates that differences among flowers on two-flower
      ramets accounted for 45.4% of the variation in selfing, differences among genets
      accounted for 16.1% of the variation, and statistical and sampling error
      accounted for 38.5% of the variation. Differences among flowers within ramets may
      reflect the order of sequential floral probes on a display.

PMID- 14666136
TI  - The involvement of suprachiasmatic nuclei in the regulation of estrous cycles in
      rodents.
AB  - Originally suprachiasmatic nuclei (SCN) were considered the main center of
      signals regulating the cyclic function of female reproduction, especially the
      gating of the LH surge. It was confirmed in the rat but not in the hamster. Some
      recent data show that multiple and complex interactions and processes underlie
      the occurrence of this very important and crucial event in female reproduction:
      the LH surge. Thanks to such multiway and multifactor control, the LH surge and
      the resulting ovulation occur regularly when "the time window" opens. Involvement
      of the SCN and other nuclei of the respective area in the regulation of rhythmic
      reproductive phenomena in female rats and hamsters is discussed.

PMID- 14666137
TI  - Pharmacokinetics of ovarian steroids in Sprague-Dawley rats after acute exposure
      to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces abnormalities in steroid
      dependent processes such as mammary cell proliferation, gonadotropin release and
      maintenance of pregnancy. In the current study, the effects of TCDD on the
      pharmacokinetics of 17beta-estradiol and progesterone were examined. Adult
      Sprague-Dawley rats were ovariectomized and pretreated with TCDD (15 microg/kg
      p.o.) or vehicle. A single bolus of 17beta-estradiol (E2, 0.3 micromol/kg i.v.)
      or progesterone (P4, 6 micromol/kg i.v.) was administered 24 hours after TCDD and
      blood was collected serially from 0-72 hours post-injection. Intravenous E2 and
      P4 in DMSO vehicle had elimination half-lives of approximately 10 and 11 hours,
      respectively. TCDD had no significant effect on the pharmacokinetic parameters of
      P4. The elimination constant and clearance of E2 were decreased by TCDD while the
      elimination half-life, volume of distribution and area under the
      time*concentration curve were not altered significantly. Overall, these results
      indicate that diminished serum progesterone and estradiol concentrations
      following exposure to TCDD are due primarily to actions on steroid synthesis and
      release rather than any alterations in pharmacokinetics.

PMID- 14666138
TI  - Local vascular pathway for progesterone transfer to the brain after nasal
      administration in gilts.
AB  - In the present study we examined whether local transfer of intranasally
      administrated tritiated progesterone (3H-P4) would increase its concentration in
      blood supplying the brain and hypophysis in comparison with other organs.
      Additionally, the effect of estrous cycle on the P4 transfer was evaluated on
      isolated gilts' heads. In the first experiment 3H-P4 was instilled into the nasal
      cavities of anaesthetized, immature pigs (n=10). Simultaneous blood samples were
      collected for radioactivity measurement every minute from the same occluded
      carotid artery through two catheters; one catheter was pointed towards the head,
      the other one towards the heart. In eight animals the ratio calculated between
      the 'head' and 'heart' samples was significantly (p<0.05) higher than 1 and
      reached a mean (+/- SEM) level of 3.23 +/- 0.81. In two animals a much higher
      ratio was observed. A head/heart ratio>1 indicates an existence of local transfer
      of 3H-P4 from venous blood to the carotid blood. In the second experiment, heads
      of 26 mature, cycling gilts were perfused through the right carotid artery with
      autologous blood. The outflow from the left carotid artery was collected as 1 min
      samples. 3H-P4 was infused into the angularis oculi veins. Transfer of 3H-P4 from
      the venous blood into the arterial blood reached the mean (+/- SEM) level of 4.11
      +/- 1.08 pg/ml on days 2-4, 3.2 +/- 0.70 on days 17-21 and 0.94 +/- 0.22 pg/ml on
      days 15-16 of the estrous cycle. No 3H-P4 transfer was observed on days 9-11.
      These findings demonstrate that nasally administered progesterone can reach the
      brain in locally higher concentration through the vascular pathway. Moreover, the
      between-vessel transfer of P4 is significantly affected by the stage of the
      estrous cycle.

PMID- 14666139
TI  - Oxidoreductive capability of boar sperm mitochondria in fresh semen and during
      their preservation in BTS extender.
AB  - The purpose of our study was to determine the effect of dilution and liquid
      preservation of boar sperm on oxidoreductive capability of their mitochondria.
      The semen was diluted with BTS extender produced from water purified by
      destillation or by reverse osmosis. The spermatozoa were stored over a four-day
      period at 16-18 degrees C. The function of sperm mitochondria was assessed using
      the screening cytochemical test for NADH-dependent oxidoreductases
      (diaphorase/NADH, related to flavoprotein). Morphological assessment of
      cytochemical reaction was carried out using a light microscope. The intensity of
      the reaction was evaluated by means of a computer image analysing system
      (Quantimet 600S), measuring the integrated optical density (IOD) and mean optical
      density (MOD) of the reaction product (formazans) occurring in the sperm
      midpieces. In the non-diluted semen, intensive cytochemical reaction throughout
      the length of the sperm midpiece was observed. Furthermore, spermatozoa with the
      intensive reaction displayed the high optical density values. After dilution the
      semen with two variants of experimental extender, and as the conservation time
      expired, the cytochemical reaction was less intensive. Moreover, the absence of
      formazan deposits in various parts of the sperm midpiece was also noted. These
      morphological features corresponded to low values of optical density. These
      findings suggest that the dilution of semen and the time of sperm preservation
      may be critical factors that handicap energy metabolism of sperm mitochondria.
      The type of water used in preparing BTS extender does not have any significant
      effect on the oxidoreductive capability of sperm boar mitochondria.

PMID- 14666140
TI  - Localization of atrial natriuretic peptide in pig granulosa cells isolated from
      ovarian follicles of various size.
AB  - The aim of the current study was to present the spatial distribution of atrial
      natriuretic peptide (ANP) in short-term cultures of pig granulosa cells obtained
      from small, medium, and large ovarian follicles. The specific immunoreactivity
      was detected by three monoclonal antibodies recognizing different epitopes of the
      ANP molecule (Mab 6C3, Mab 6F11, Mab5D3). The specific ANP immunoreactivity
      detected by Mab 6C3 and Mab 6F11 showed dense staining of cytoplasm and was
      similar in granulosa cells from small and medium follicles. The strongest ANP
      immunostaining was observed in GC obtained from large follicles. The ANP
      immunostaining detected by Mab 5D3 had granular appearance moderately expressed
      in the submembrane region of granulosa cells of all types of follicles. Since ANP
      and ANP receptors are present in reproductive organs, the three anti-ANP
      antibodies may be an useful tool in further studies concerning the role of ANP in
      granulosa cell differentiation and function.

PMID- 14666141
TI  - The role of insulin-like growth factor-I in neuroendocrine function and the
      consequent effects on sexual maturation: inferences from animal models.
AB  - It is known that growth hormone (GH) plays an important role in growth and
      development.Additionally, emerging evidence suggest that it also influences
      hypothalamic-pituitary-gonadal function. We have found that GH from different
      species has different effects in mice. In rodents, human GH (hGH) binds to both
      GH and prolactin (PRL) receptors; it has both somatotrophic and lactotrophic
      effects. Since PRL has a profound effect on neuroendocrine function, the results
      obtained from hGH treatment or from transgenic animals expressing the hGH gene
      reflect PRL-like effects of this hormone. However, bovine GH (bGH) is purely
      somatogenic and therefore the effects of bGH represent the function of the
      natural GH produced in rodents. Furthermore, our studies in mice and rats have
      shown that not all effects of GH are stimulatory and the duration of exposure of
      the hypothalamo-hypophyseal-gonadal system to GH might influence the secretions
      of gonadotropins and gonadal steroids. In humans, excess productions of GH in
      acromegaly and GH resistance in Laron syndrome adversely affect reproduction.
      Similarly, it has been demonstrated that in transgenic mice expressing various GH
      genes, in insulin-like growth factor-I (IGF-I) gene-knockout mice, in GH receptor
      gene-disrupted (GHR-KO) mice, and in Ames dwarf mice the onset of puberty and/or
      fertility is altered. Therefore, excess or subnormal secretion of GH can affect
      reproduction. We have shown that the hypothalamic-pituitary functions are
      affected in transgenic mice expressing the GH genes, Ames dwarf mice and in GH
      receptor gene knockout mice. The majority of the GH effects are mediated via IGF
      I and the aforementioned effects may be due to the GH-induced IGF-I secretion or
      due to the absence of this peptide production. It is important to realize that
      the syntheses and actions of IGF binding proteins are controlled by IGF-I.
      Furthermore, some IGF binding proteins can inhibit IGF-I action. Therefore, the
      concentrations of IGF binding proteins and the ratio of these binding proteins
      and IGF-I within the body might play a pivotal role in modulating IGF-I effects
      on the neuroendocrine-gonadal system.

PMID- 14666142
TI  - Effect of central infusions of neuropeptide Y on GnRH/LH axis in ewes during the
      early anoestrous period.
AB  - Neuropeptide Y (NPY) is a putative mediator of many physiological processes in
      the central nervous system including reproductive functions. In this study we
      examined the effect of NPY on the GnRH/LH secretory activity in early anoestrous
      ewes. Crossbreed ewes one week (group 1w, n=7) and six weeks (group 6w, n=7)
      after the last oestrous cycle were infused with Ringer solution (control) or 50
      microg of NPY to the third ventricle for 5 minutes. Blood samples were collected
      during the days of infusion over six hours at ten minute intervals and then the
      ewes were slaughtered and their brains fixed in situ. Immunoreactive (ir) GnRH in
      the median eminence and LH cells in the adenohypophysis were localised by
      immunohistochemistry technique. Data were generated using computer analysis to
      determine the optical density for immuno-staining and the proportion of ir LH
      cells. Plasma LH was determined by radioimmunoassay. It was found that
      investigated anoestral groups differed only in the optical densities of ir GnRH
      and ir LH, which were lower in group 6w compared to group 1w (p<0.001). LH
      concentrations and parameters of pulsatile LH secretion were similar in both
      anoestral groups. Acute NPY infusions induced in group 1w decreased both in ir
      GnRH and ir LH optical densities and in area fraction for ir LH cells (p<0.001)
      whilst it increased in plasma LH concentration (p<0.05) compared to vehicle
      infused animals. There was no changes in the secretory activity of the GnRH/LH
      axis following NPY infusion in group 6w. In conclusion, we suggest that NPY may
      be involved in the central regulation of reproductive function in ewes, however,
      the sensitivity of the GnRH/LH axis to NPY modulation declines throughout the
      early anoestrous period.

PMID- 14666143
TI  - Histology of salmonid testes during maturation.
AB  - The commonly applied classification systems of fish gonad maturity divide the
      maturation process into certain stages. However, the scales do not entirely
      reflect the continuity of the maturation process. Based on light microscope
      observations, the paper describes a comprehensive pattern of testicular
      transformations during maturation. The study was carried out on precocious
      underyearling and 1-year-old males of sea trout (Salmo trutta m. trutta L.), 1
      year-old males of salmon (Salmo salar L.), and males of brown trout (Salmo trutta
      m. fario L.) aged from 7 months to 4 years. A total of 821 gonads collected
      during all seasons of the year were examined. The fish were fixed in Bouin's
      fluid. Histological slides of the mid-part of the gonad were made using the
      standard paraffin technique. The 3-6 microm sections were stained with Heidenhain
      haematoxylin. Histological changes of testes during maturation were similar in
      the three species studied. Immature and resting gonads contained type A
      spermatogonia in lobules only. The appearance of cystic structures containing
      type B spermatogonia in the lobules signalled the beginning of the sexual cycle
      in male gonads. Type B spermatogonia underwent synchronous mitotic divisions
      resulting in an increase in the total number of spermatogonia. As the
      spermatogenesis continued, the gonads showed a gradual increase in the number of
      cysts containing cells at all the spermatogenetic stages: type B spermatogonia,
      primary and secondary spermatocytes, spermatids, and spermatozoa. The well-formed
      spermatozoa were released to the lobule lumen once the Sertoli cells and
      spermatozoa connections broke up and the cyst disappeared. This was a continuous
      process observed throughout the spawning season. The spermatozoa were moved to
      the efferent duct. While some of the germ cells were completing spermatogenesis,
      the lobules contained less and less cysts with type B spermatogonia, primary and
      secondary spermatocytes, and spermatids; eventually all the cells completed
      spermatogenesis. At the end of maturation, vacuoles, up to 18.9 microm in final
      diameter (brown trout), appeared in the Sertoli cells. The vacuoles were visible
      in the lobule wall epithelium for a prolonged period of time. In most salmonid
      individuals examined, the reproductive cycles were observed to overlap. In some
      fish, the preparation for another cycle began very early, i.e., at the and of
      preceding spermatogenesis, which had not been observed before. Gonad maturation
      in some males was incomplete.

PMID- 14666144
TI  - The effects of estradiol on beta-endorphin, GnRH and galanin content in the
      oviduct and the uterus of ovariectomized gilts.
AB  - Steroid hormones are known to affect synthesis and/or release of some peptides in
      the central nervous system and peripheral tissues. In the present study we
      determined changes in beta-endorphin, GnRH and galanin contents in uterine and
      oviductal tissues of ovariectomized (OVX) gilts following treatment with
      estradiol benzoate (EB) at a dose inducing a preovulatory-like LH surge. Seven
      month old gilts (90-100 kg of body weight; BW) were used in the study. Four weeks
      after ovariectomy, experimental animals were injected intramuscularly with EB (15
      microg/kg BW) at 24 h (n=5), 48 h (n=6) or 72 h (n=5) before slaughter. Three
      control gilts received corn oil vehicle. Tissues were sampled from the ampulla
      and isthmus of the oviduct and from the perioviductal, middle and paracervical
      regions of the uterine horn for determination of beta-endorphin, GnRH and galanin
      content. Significant increases of beta-endorphin content were found in all
      regions of the uterus either 24 h or 48 h after priming with EB. In oviductal
      tissue, beta-endorphin concentration only tended to increase in response to EB.
      GnRH content in tissues originating from gilts receiving EB fluctuated from a
      stimulation in the ampulla of the oviduct and in the paracervical uterus to an
      inhibition in the middle part of the uterus. A significantly increased
      concentration of galanin in response to EB was observed exclusively in the
      paracervical part of the OVX pig uterus. The results suggest an involvement of
      beta-endorphin, GnRH and galanin in the regulation of uterine function in pigs
      during the periovulatory period.

PMID- 14666145
TI  - Effect of antioxidants added to boar semen extender on the semen survival time
      and sperm chromatin structure.
AB  - The aim of the experiment was to determine the effect of potential antioxidants
      (adenosine, L-cysteine hydrochloride, ascorbic acid, magnesium fumarate and
      prolactin) supplementing the Biosolwens extender on semen survival time and sperm
      chromatin structure. The semen motility was examined every day and the
      susceptibility of sperm chromatin to denaturation was evaluated on collection day
      and day 15 of storage. The addition of magnesium fumarate to Biosolwens extender
      increased sperm survival but resulted in the highest increment in the proportion
      of sperm with damaged chromatin. Biosolwens supplemented with 200 mg of L
      cysteine hydrochloride brought the best results. It is possible that lower
      concentrations of this component would act in a more protective manner. The
      examination of the chromatin structure appears to be an useful tool for
      investigation of semen preservation.

PMID- 14666146
TI  - Role of LH in controlled ovarian stimulation.
AB  - Controlled ovarian stimulation has become an integral part of infertility
      treatment. Specific gonadotropin based protocols become the main strategies for
      controlled stimulation. To avoid the potentially detrimental effect of premature
      LH surge on oocytes and/or endometrium development, the GnRH analogs have been
      incorporated into controlled ovarian stimulation strategies. With the
      availability of recombinant gonadotropins (i.e. recombinant FSH devoided of LH
      activity) it is necessary to establish precise role of LH in the folliculogenesis
      and endometrium development. The benefit of exogenous LH may vary with the GnRH
      agonists and antagonists regiment used. The optimal amount of LH or ratio FSH to
      LH used during therapeutically stimulated growth of follicles is still a problem
      that needs to be solved in the near future.

PMID- 14666147
TI  - Quantitative aspect of gene expression analysis in mammalian oocytes and embryos.
AB  - In vitro produced embryos, due to their lower developmental potential when
      compared to the in vivo derived counterparts, have been currently subjected to an
      intensive scientific investigation. Qualitative as well as quantitative analyses
      of gene expression (reverse transcription-polymerase chain reaction; RT-PCR)
      belong to the powerful tools providing a wide spectrum of data on the quality of
      oocytes and embryos. The main research areas in this topic concern the following
      categories: oocyte quality, developmental competence of in vitro produced (IVP)
      embryos also with regard to their sex, embryo metabolism, gene expression levels,
      embryo manipulation and cloning. There are many methods that have been applied to
      study gene expression, but only some of them meet the requirement of analysing
      small cell samples which usually is the case with oocytes or early embryos. This
      paper deals with the description of the current methods commonly used for
      quantitative gene expression in mammalian oocytes and preimplantation embryos
      with a special attention paid to the real time PCR.

PMID- 14666148
TI  - Secretory activity of boar seminal vesicle glands.
AB  - This paper reviews the recent research on the physiological role of peptide and
      protein substances synthesized in boar seminal vesicle glands. Secretions from
      these glands are the major components of seminal plasma. Unique biochemical
      properties of seminal vesicle proteins, which determine their numerous functions
      in the reproductive processes, are discussed. The discovery of phosphotyrosine
      acid phosphatase in boar seminal vesicle secretions and the first description of
      the biochemical properties of platelet activating factor acetylhydrolase (PAF-AH)
      have led to remarkable inroad in molecular andrology. The fundamental role of
      vesicular low and high molecular antioxidants in the protective function against
      reactive oxygen species (ROS) is defined. Emphasis is also given to the role of
      androgens in controlling the secretory activity of boar seminal vesicles.

PMID- 14666149
TI  - Melatonin--a modulator of the GnRH/LH axis in sheep.
AB  - The nocturnal secretion of pineal melatonin provides information to vertebrates
      on changes in day length under the circumstances in which they live. In sheep,
      which are seasonal breeders, the secretion of melatonin is also a signal to the
      neural structures controlling the secretion of gonadotropins from the pituitary
      gland to drive their activity in accordance with the season of the year. The
      sites and mechanisms of melatonin action on GnRH/LH secretion has been the
      subject of intensive studies in the last decade. This article briefly reviews the
      most important discoveries and methods used in this research, which has led to a
      better understanding of the role of melatonin in the modulation of hypothalamo
      pituitary-gonadotropic axis activity in sheep. The identification of melatonin
      receptors within the central nervous system and in the pars tuberalis of the
      pituitary gland, as well as the use of specific techniques of micro-implantation
      and micro-infusion were crucial in this aspect.

PMID- 14666150
TI  - Influence of dietary fatty acids composition, level of dietary fat and feeding
      period on some parameters of androgen metabolism in male rats.
AB  - The aim of the present study was to determine the effect of the composition of
      dietary fatty acids, the duration of feeding period and dietary fat level on
      androgen metabolism in male rats. One hundred and twelve Wistar rats were divided
      into 18 groups which were fed three diets containing different types of fat
      (rapeseed [R], palm [P] and fish [F] oil) at either normal fat level (w/w; 5%) or
      high fat level (20%) during one, three or six weeks. Blood plasma level of
      androgen (testosterone+dihydrotestosterone) and testicular activity of 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) were investigated. In addition,
      androgen content in cytosol of the heart, the target organ, was measured.
      Androgen concentration in both blood plasma and heart cytosol extracts was
      measured by radioimmunoassay. The activity of 17Beta-HSD was expressed as a
      conversion of [3H]androstendione to [3H]testosterone in soluble fraction of
      gonadal homogenates. Plasma androgen concentration was influenced by a type of
      dietary fat (p<0.05). The highest plasma level of androgen was observed in
      animals fed R diets rich in unsaturated fatty acids. Significantly lower androgen
      concentration was demonstrated in rats fed P diets rich in saturated fatty acids.
      Only the feeding period factor significantly influenced androgen content in
      cytosol fraction of heart muscle cells (p<0.01). A positive correlation was found
      between plasma androgen concentration in plasma and cytosol fraction of the heart
      muscle cells (r=0.63, p<0.001). The feeding period (p<0.001) and dietary fat type
      (p<0.05) significantly affected the activity of 17beta-HSD. The least 17beta-HSD
      activity was observed in animals consuming the P-20% diet for six weeks. In
      summary, dietary fat type and feeding period, but not fat level, significantly
      affected both testosterone production and testosterone uptake by the target organ
      in male rats. It was found that a rapeseed diet rich in unsaturated fatty acids
      stimulated the testicular function in rats.

PMID- 14666151
TI  - The effect of the intramammary infusion of Escherichia coli endotoxin on
      ovulation in lactating dairy cows.
AB  - The purpose of this experiment was to determine if intramammary inflammation
      during the periovulatory period affects the occurrence of ovulation in lactating
      dairy cows. Ten lactating, cyclic, Holstein dairy cows received 2 injections of
      prostaglandin F2alpha at eleven-day intervals, to synchronize luteolysis. The day
      of the second injection was designated as day 0. Ovulation was anticipated to
      occur 3-5 days later (on days 3-5). Beginning at the morning milking on day 1,
      cows received intramammary infusions of either Escherichia coli endotoxin (10
      microg; n=5) or infusion vehicle (pyrogen free Hank's balanced salt solution;
      n=5) into 2 quarters immediately after milking. The same quarters were infused
      after each milking through day 4. Venous blood samples were collected daily from
      day -1 through 13 for determination of progesterone to monitor luteolysis and
      formation of a new corpus luteum. Blood samples were also collected at 4-h
      intervals (days -1 to 2), then at 2-h intervals (days 2 to 5) to measure
      concentrations of luteinizing hormone. Ovaries were examined ultrasonographically
      on days -1 through 5 and on day 12 to monitor follicular growth and formation of
      the corpus luteum. Collectively, these observations were used to determine if and
      when ovulation occurred. Intramammary infusion of E. coli endotoxin induced an
      immediate increase in the concentration of somatic cells in milk from treated
      quarters. However, this treatment had no effect on the occurrence or timing of
      ovulation. Based on ultrasonography and concentrations of progesterone, four of
      five cows in each treatment group appeared to have ovulated. Preovulatory surges
      of LH were detected within the intensive bleeding periods for three cows in each
      treatment group. The magnitude of the LH surge was reduced in cows receiving
      endotoxin.

PMID- 14666152
TI  - Uterine blood supply as a main factor involved in the regulation of the estrous
      cycle--a new theory.
AB  - The paper presents a new theory on the physiological mechanism of initiation of
      luteolysis, function of endometrial cells and protection of corpus luteum. This
      theory is based on previous studies published by the authors and their coworkers
      on the retrograde transfer of PGF2alpha in the uterine broad ligament vasculature
      during the estrous cycle, early pregnancy and pseudopregnancy. The studies were
      focused on cyclic changes in uterine blood supply and the apoptosis of
      endometrial cells. Moreover, the results of many other authors are cited. The
      statements of the theory are as follows: 1. The initiation of luteolysis is a
      consequence of regressive changes in the endometrium which are due to the
      reduction of the uterine blood supply below the level necessary to provide for
      the extended needs of active endometrium. 2. During the luteal phase, both a
      considerable increase in uterine weight and a decrease in blood flow through the
      uterine artery, resulting from increasing progesterone concentration, reduce the
      uterine blood supply. In comparison to the volume of blood flowing to the porcine
      uterus during the estrus period, only 30-40% of the blood volume is determined on
      day 12 of the estrous cycle. The uterine weight at that time is 40-60% larger
      than that in the early luteal phase. Thus, due to the considerable constriction
      of uterine blood vessels, there is a discrepancy between the requirement for
      oxygen and other factors transported by blood and the possibility of supplying
      the uterus with these substances. After reaching the threshold of uterine blood
      supply level, which in pigs takes place around day 12 of the estrous cycle,
      regressive changes and PGF2alpha release from endometrial cells occurs. 3.
      Estrogens and progesterone are the major factors affecting blood flow in vessels
      supplying the uterus. The factors that modulate, complement and support
      vasodilation and vasoconstriction are: PGE2, LH, oxytocin, cytokines,
      neurotransmitters and other local blood flow regulators. In some animal species
      these modulators, especially those of embryonic origin, may be crucial for the
      status of uterine vasculature. 4. During early pregnancy, the action of embryo
      signals (estrogens, cytokines), endometrial PGE2 as well as LH results in the
      relaxation of the uterine artery (pigs: day 12) and, consequently, in an increase
      in uterine blood supply. This reaction of the maternal recognition of pregnancy
      effectively prevents regressive changes in well developed endometrial cells to
      occur. 5. Local uptake and retrograde transfer of PGF2alpha into the uterine
      lumen during early pregnancy protects corpus luteum from PGF2alpha luteolytic
      action. 6. During the period of regressive changes resulting from the limited
      uterine blood supply, endometrial cells restrain PGF2alpha synthesis. They are,
      however, still capable of releasing prostaglandin when uterine blood supply is
      improved after the embryo appears in the uterus. This potential capability for
      PGF2alpha synthesis was demonstrated in in vitro studies when endometrial cells
      collected during its regressive phase were incubated in medium and stimulated by
      LH and oxytocin. 7. Prostaglandin F2alpha pulses in venous blood flowing from the
      uterus do not confirm pulsatile secretion of PGF2alpha. The pulses may result
      from the pulsatile excretion of PGF2alpha with venous blood according to the
      rhythmic uterine contractions associated with oxytocin secretion. 8. The results
      supporting this concept are presented and discussed in due course. The critique
      of Bazer and Thatcher's theory on exocrine versus endocrine secretion of
      prostaglandin F2alpha during the estrous cycle is also depicted.

PMID- 14666153
TI  - Local adjustment of blood and lymph circulation in the hormonal regulation of
      reproduction in female pigs--facts, conclusions and suggestions for future
      research.
AB  - Arteries, veins, capillaries and lymphatic vessels situated in the mesovarium and
      mesosalpinx of domestic animal species (pig, cow, sheep) form the periovarian
      vascular complex. Particular components of the periovarian vascular complex
      interact functionally and morphologically creating a specific environment for
      numerous physiological processes. The complex plays an essential role in the
      system of the retrograde transfer of the ovarian hormones. This phenomenon is
      especially well documented in pigs. The efficiency of the retrograde transfer of
      estradiol and progesterone from blood and lymph leaving the gonad to blood of the
      ovarian artery (expressed as percentage of their concentration in the ovarian
      venous blood) as well as the rate of the retrograde transfer of these hormones to
      the ovary (measured in nanograms or picograms per minute) is presented and
      discussed in this paper. No simple relationship was found between hormone
      concentration in ovarian venous effluent and the efficiency or the rate of their
      retrograde transfer during the estrous cycle. It appears that two processes
      contribute to the highly efficient retrograde transfer of ovarian hormones into
      the ovary in the periovarian vascular complex: 1/ direct hormone permeation from
      the ovarian vein into the adjacent branches of the ovarian artery through the
      counter-current mechanism; 2/ indirect permeation of ovarian hormones consisting
      of two stages. The first stage includes the permeation of hormones from lymph
      leaving the ovary via the subovarian lymphatic vascular network as well as lymph
      and venous blood, leaving the mesosalpinx and going to capillaries and tiny
      venous vessels in the entire mesovarium. These tiny mesovarium vessels connect
      and then branch out again to form the veno-venous network on the surface of
      branches of the ovarian artery. The second stage includes the permeation of
      hormones from the veno-venous blood into the branches of the ovarian artery. The
      authors present a hypothesis that the retrograde transfer of ovarian hormones may
      participate in the feedback regulation of ovarian function. The relationship
      between the retrograde transfer of ovarian hormones in the area of periovarian
      vascular complex and local elevation of steroid hormone concentrations in blood
      supplying the oviduct and uterus is presented. The paper also includes
      suggestions for future research.

PMID- 14666154
TI  - Circulating concentrations of luteinizing hormone, testosterone, and growth
      hormone after naloxone treatment in sexually mature boars.
AB  - The effects of naloxone, an antagonist of opioid peptides, on circulating
      concentrations of luteinizing hormone (LH), testosterone, and growth hormone (GH)
      were determined in sexually mature boars. Blood samples were collected at 15-min
      intervals for three hr from five crossbred boars. Two hr after initiation of
      blood sampling, boars received an i.v. challenge of naloxone (1 mg/kg body
      weight; n=2) or 0.9% saline (n=3). Twenty-four hr later the experiment was
      repeated, but boars that previously received naloxone received saline and vice
      versa. A time by treatment interaction (p=0.09) was detected for concentrations
      of LH in serum, and levels of LH were greater (p<0.03) after treatment with
      naloxone compared to saline. Concentrations of testosterone in serum were
      affected by time (p<0.01), but not treatment (p= 0.59) or treatment by time
      (p=0.74). A treatment by time interaction (p=0.02) was detected for serum GH
      concentrations. Levels of GH increased in saline-treated boars (p<0.01), but not
      in boars receiving naloxone (p>0.1). Our results are consistent with the theory
      that opioid peptides suppress LH secretion and stimulate GH release in sexually
      mature boars.

PMID- 14666155
TI  - Evaluation of mouse preimplantation embryos exposed to oxidative stress cultured
      with insulin-like growth factor I and II, epidermal growth factor, insulin,
      transferrin and selenium.
AB  - Blastocyst culture requires strictly defined culture media to sustain its
      viability and quality. Although blastocyst media are commercially available, they
      do not meet all the needs and research focused on blastocyst-promoting agents is
      on the way. The aims of the study were to evaluate the significance of insulin
      like growth factors I (IGF-I) and II (IGF-II); epidermal growth factor (EGF) and
      a mixture of insulin, transferrin and selenium (ITS) on the development of
      embryos exposed to oxidative stress. C3B6F1 mice were stimulated with 5 IU of
      pregnant mare serum gonadotropin following by administration of 5 IU of equine
      chorionic gonadotropin and mating with DBA males. The mice were killed 40 h after
      eCG injection by cervical dislocation and then the 2 cell embryos were flushed
      out from the fallopian tubes. To evaluate whether the growth factors may
      compensate the unfavorable--oxidative milieu created by hydrogen peroxide (H2O2),
      the embryos were transferred to 1/ control medium, 2/ control medium+0.1 mM
      (H2O2) or 3/ control medium+H2O2 enriched with 10(-7) g/ml of IGF-I, IGF-II, EGF
      or a mixture of insulin (5x10(-6) g/ml), transferrin (5 x10(-6) g/ml) and
      selenium (5x10(-9) g/ml; ITS). Embryos were evaluated 96-144 hours following eCG
      injection. In the study the dynamics of embryo development and blastocyst cell
      numbers (including inner cell mass) were assessed. The morphological evaluation
      comprised viability and apoptosis (TUNEL). In oxidative stress setting, IGF-I,
      IGF-II, EGF and ITS minimized the negative influence of H2O2, and embryos
      developed faster than in control conditions. Blastocysts cultured with hydrogen
      peroxide and growth factors or ITS displayed normal morphology and had more cells
      -also within the inner cell mass--than those treated only with H2O2. The positive
      TUNEL reactions were sporadically observed in embryos cultured with hydrogen
      peroxide supplemented with growth factors. IGF-I, IGF-II, EGF and ITS have a
      positive effect on pre-implantation embryo development in detrimental culture
      conditions of oxidative stress.

PMID- 14666156
TI  - In vitro production of ovarian steroids in yellow perch (Perca flavescens):
      effects of photothermal manipulation, gonadotropin and phorbol ester.
AB  - We investigated the capacity of ovaries of yellow perch to produce steroid
      hormones in vitro and the ovarian response to gonadotropin and phorbol ester
      during the annual reproductive cycle. The effects of photothermal manipulation on
      perch gonadal steroidogenesis and its regulation have also been examined.
      Initially, all females kept indoors were exposed to the same water temperature
      and photoperiod. By the end of August, following the first sampling, fish were
      submitted to different photothermal regimes. Group A was maintained under
      photothermal conditions characteristic for southern Ohio. Group B was submitted
      to a condensed light/temperature regime designed to accelerate physiological
      changes that depend on photothermal stimuli. In group A, basal in vitro
      production of ovarian estradiol (E2) was the highest in October and November, and
      hCG significantly stimulated E2 secretion during the entire period of
      vitellogenesis (October-January). In this group, the highest production of basal
      testosterone (T) was observed before spawning. hCG-stimulated production of T was
      highest at the beginning of vitellogenesis. Gonadotropin stimulated T production
      before spawning, a time when gonadotropin was unable to stimulate E2 production.
      Phorbol ester (PDBu) stimulated E2 and T production during vitellogenesis at the
      same time points as hCG did (E2: December, January; T: December). hCG-stimulated
      T production was not mimicked by PDBu in April. Condensing of the photothermal
      cycle resulted in diminished ovarian production of E2 during vitellogenesis.
      Moreover, the fish submitted to a condensed photothermal cycle demonstrated
      augmented T production during the postvitellogenic stage of ovarian development.
      Ovaries of group B did not respond to PDBu. Generally, the seasonal fluctuations
      in ovarian capacity to produce E2 and T as well as in gonadal responsiveness to
      gonadotropin observed in female yellow perch illustrate the dynamic nature of
      ovarian endocrine function. The lack of response to gonadotropin with regard to
      E2 production prior to spawning is not due to insensitivity to gonadotropin, but
      rather due to some deficiency in steroidogenesis (e.g. reduced aromatase
      activity). It appears also that ovarian steroidogenesis and its regulation are
      dependent on annual changes of photothermal conditions.

PMID- 14666157
TI  - Primary antisera against selected steroids or proteins and secondary antisera
      against gamma-globulins--an available tool for studies of reproductive processes.
AB  - This paper presents characteristics of different polyclonal antisera raised
      against several steroid and protein antigens: 1/ primary antisera against steroid
      hormones: estradiol-17beta (anti-E2), estrone (anti-E1), testosterone (anti-T),
      androstendione (anti-A4), cortisol (anti-F) and corticosterone (anti-B); 2/
      primary antisera against porcine luteinizing hormone (anti-pLH) and against
      different forms of porcine pregnancy associated glycoproteins (anti-pPAG) -
      proteins produced by chorionic tissue; 3/ secondary monovalent antisera raised
      against rabbit gamma-globulins (Sm-r); 4/ secondary polyvalent antisera against
      rabbit, pig and quinea pig gamma-globulins mixed at a ratio 1:1:1 (Sp-rpq). All
      antisera described in the paper present sufficient quality to be routinely used
      in various RIA, ELISA or Western determinations in physiological and clinical
      studies of reproductive processes. The antisera against steroid hormones and pLH
      are available on request.

PMID- 14666158
TI  - The testicular aromatase: from gene to physiological role.
AB  - The aromatase is the terminal enzyme responsible for estrogen biosynthesis. It is
      present in the endoplasmic reticulum membrane of steroidogenic cells. The
      aromatase gene is unique and its expression is regulated in a tissue and more
      precisely, in a cell-specific manner via the alternative use of various promoters
      located in the first exon I. Physiological role of estrogens in the regulation of
      mammalian testicular functions is indicated by: 1/the aromatase gene expression
      and its transduction in a fully active protein in somatic cells as well in germ
      cells of testes, 2/ the widespread distribution of estrogen receptors (ERalpha
      and ERbeta) in the genital tract of the male. Our recent data showing that human
      ejaculated spermatozoa expressed specific transcripts for P450arom support and
      expand the observations reported in germ cells of other mammalian species.
      Therefore, female hormones (or the ratio androgens/estrogens) do play a role,
      either directly on germ cells or via testicular somatic cells, in the maintenance
      of male gonadal functions. Several steps, including spermatid production, the
      sperm maturation and/or survival provide opportunity for estrogen action.

PMID- 14666159
TI  - Modulation of growth hormone, luteinizing hormone, and testosterone secretion by
      excitatory amino acids in boars.
AB  - Ketamine hydrochloride, an n-methyl-d-aspartate (NMDA) receptor antagonist was
      used in an experiment that tested the hypothesis that fasting-induced increases
      in growth hormone (GH) secretion is mediated by excitatory amino acid (EAA)
      neurotransmission in boars. The effects of the drug on circulating concentrations
      of luteinizing hormone (LH) and testosterone were also evaluated. Blood was
      sampled at 15-min intervals for 8 h from 12 boars fitted with jugular vein
      catheters. At Hours 4 and 6, fasted boars (feed was withdrawn 48 h before the
      start of blood sampling) received i.m. injections of ketamine (19.9 mg/kg body
      weight; n=4) or .9% saline (n=4). Boars allowed feed on an ad libitum basis (n=4)
      received i.v. injections of n-methyl-d,l-aspartate (NMA; 2.5 mg/kg body weight),
      an NMDA receptor agonist, at Hours 4 and 6. Secretion of GH increased after NMA
      injections but was unaffected by treatment with ketamine or saline. Circulating
      concentrations of LH and testosterone were increased by injections of ketamine
      but were unaffected by injections of NMA or saline. Our results suggest that NMA
      is a potent GH secretagogue, but do not support the hypothesis that EAA
      neurotransmission drives the increased GH secretion displayed in fasted boars.
      Our finding that ketamine increased LH and testosterone release supports the
      notion that EAA have inhibitory effects on gonadotropin secretion in acutely
      fasted swine.

PMID- 14666160
TI  - Effects of mating stimuli and oxytocin on plasma cortisol concentration in gilts.
AB  - The involvement of oxytocin (OT) in the regulation of glucocorticoid secretion
      during stress reaction, parturition, and suckling has been documented in various
      species. In this study four in vivo experiments were conducted on gilts (1) to
      demonstrate the influence of mating stimuli on plasma cortisol concentration, (2)
      to test the effect of OT alone and (3) OT combined with OT-antagonist on cortisol
      secretion and (4) to clarify the role of progesterone and estradiol in cortisol
      response to exogenous OT. In experiment 1, plasma cortisol concentration in gilts
      (n=4) increased (p<0.05) from 16.1 +/- 5.3 ng ml(-)1 (control period: 30 min
      before mating) to 42.8 +/- 11.6 ng ml(-1) and 46.6 +/- 9.6 ng ml(-1) at the time
      of leaving the pen and during the first visual and olfactory contact with the
      boar, respectively. During coitus the elevation was maintained (48.8 +/- 9.8 ng
      ml(-1); p<0.05 vs. control). The plasma cortisol concentration returned to pre
      mating levels within 30 min after mating. In experiment 2, gilts (n=7) were
      treated, according to Latin square design, with saline (2 ml; i.v.) and OT (10,
      20, and 30 IU; i.v.). The magnitude of cortisol response (area under cortisol
      curve) was higher (p<0.01) only after treatments with 20 and 30 IU OT vs. control
      period (30 min before OT). Gilts (n=3) of experiment 3 were infused with OT
      antagonist (Atosiban; 25 mg per gilt per 2 hours; i.v.) and then were injected
      with OT (20 IU; i.v.) 60 min after the beginning of Atosiban administration.
      Blockage of OT receptors by Atosiban reversed the stimulatory effect of OT on
      cortisol secretion. In experiment 4, ovariectomized gilts (n=25) primed (i.m.)
      with corn oil (n=7), progesterone (P4; n=7), estradiol benzoate (EB; n=4) or
      EB+P4 (n=7) were treated with OT (20 IU; i.v.). Plasma cortisol concentrations
      were increased following OT administration in all gilts of experiment 4. The
      highest cortisol response to OT was noted in gilts primed with EB+P4 (p<0.01 vs.
      other groups). IN CONCLUSION: (1) leaving the pens, visual and olfactory contact
      with the boar as well as coitus, increased plasma cortisol concentrations in
      gilts to similar levels; (2) exogenous OT (20 and 30 IU per gilt) increased
      cortisol plasma concentration, (3) this effect was abolished by OT-antagonist and
      (4) E2+P4 elevated cortisol response to OT. Oxytocin may be included to
      secretagogues of the hypothalamus-pituitary-adrenocortical axis in pigs.

PMID- 14666161
TI  - Pattern of follicular development in high fecundity Olkuska ewes during the
      estrous cycle.
AB  - Folliculogenesis was studied daily in the 18 oestrous cycles in six prolific
      Olkuska ewes from October to December using transrectal ultrasonography to record
      the number and size of all ovarian follicles > or =2 mm in diameter. Blood
      samples were taken once a day and were analyzed for concentrations of FSH, LH,
      estradiol and progesterone. Follicular and hormonal data were analyzed for
      associations between different stages of development of the follicular waves and
      concentrations of FSH and estradiol. The first wave during which at least one
      follicle reached maximum diameter of > or =4 mm after ovulation, was defined as a
      wave 1, and the following waves were numbered sequentially. Waves 1, 2, 3, 4 and
      the ovulatory one emerged on days: -2 to 4, 4 to 8, 6 to 11, 10 to 12 and 11 to
      15, respectively. The mean number of follicles per wave that reached diameter of
      > or =4 mm was 4.15 +/- 1.1 and 16.62 +/- 8.6 follicles per estrous cycle of a
      total 299 follicles were observed. Significantly more follicles (p> or =0.05)
      emerged on days 2, 8 and 13 than in other days. Serum FSH concentrations
      fluctuated from 0.11 ngml(-1) on day 2 to preovulatory maximum 1.81 ngml(-1) on
      day 17 of the estrous cycle. The emergence of follicular waves was associated
      with elevations of FSH concentrations in blood serum. The mean increase in FSH
      concentration was followed by the recruitment of follicles of the next wave. The
      mean daily FSH concentration and the mean number of follicles emerging each day
      were negatively correlated. The length of the interwave interval (4.4 +/- 1.6
      days) did not differ significantly from the interval between pulses of FSH (4.8
      +/- 0.3 days). The mean serum estradiol concentrations showed fluctuations until
      day 14 and then gradually increased from 5.47 +/- 0.3 pgml(-1) to reach a peak
      13.14 +/- 0.2 pgml(-1) on the day before ovulation. To summarize, the growth of
      ovarian follicles during the estrous cycle in high fecundity Olkuska sheep
      exhibited a distinct wave-like pattern. Ovarian follicles emerged from the pool
      of 2 mm follicles. The preovulatory follicles originated from the large follicle
      population were present in the ovary at the time of luteal regression. The
      initial stages of the growth of the largest follicles appears to be controlled
      primarily by increases in FSH secretion.

PMID- 14666162
TI  - Study of transcripts from AC010088, a 199,485 bp fragment of the human Y
      chromosome located in the azoospermia factor region c.
AB  - Deletions on the long arm of the human Y chromosome are associated with male
      infertility. In this work, we studied transcripts of a 199,485 bp long fragment
      of the Yq11 region (GenBank accession number, AC010088) located in the AZFc
      (azoospermia factor region c), and characterized their gene structures. After
      masking repetitive elements, we searched human mRNA Refseqs (reference
      sequences), a dbEST (database of expressed sequence tags) and a non-redundant
      nucleic acid database for the mRNAs and ESTs corresponding to the AC010088 using
      the BLAST programs at the NCBI (National Center for Biotechnology Information)
      site. Our findings are summarized as follows: i) BPY2 (testis basic protein on Y,
      2), DAZ1 (deleted in azoospermia 1), TTY4 (testis transcript Y 4) mRNAs and 23
      ESTs were found; ii) Eighteen of 23 ESTs were transcripts of the DAZ gene(s), one
      EST was a transcript of TTY4 gene, and the remaining 4 probably corresponded to 4
      different pseudogenes; iii) DAZ gene(s) were expressed not only in testis, but
      also in lung carcinoma cells, stomach and Ewing's sarcoma cells; iv) beta
      satellite clusters were present around and within the BPY2 and TTY4 gene region;
      v) In this study, TTY4, BPY2 and DAZ1 genes were mapped precisely to the AC010088
      region.

PMID- 14666163
TI  - Involvement of nitric oxide in inflammation of ovaries in gilts.
AB  - NADPH-diaphorase (NADPH-d) and an inducible type of nitric oxide synthase (iNOS)
      were demonstrated in porcine ovaries after unilateral infusion of bacteria into
      the hilus of an ovary. In group I one ml of saline was infused into the hilus of
      each ovary from the 15th day to the 19th day of the estrous cycle. In group II
      one ml of bacterial suspension (10(9) colony forming units of Escherichia coli,
      Staphylococcus aureus and Corynebacterium pyogenes, in a proportion 1:1:1,
      respectively) in saline was infused into the hilus of one ovary on days
      corresponding to those of the control group (gr. I), whereas saline was infused
      into the contralateral ovary. The ovaries were collected on the 7th day of the
      next estrous cycle. In the bacteria-treated ovary, the activity of NADPH-d was
      higher in the endothelium of blood vessels, corpora lutea and follicular walls in
      comparison to that observed in the respective structures of the contralateral
      ovary. The highest activity of NADPH-d was found in the vascular endothelium in
      the bacteria-infused ovary. Vascular smooth muscle cells found in both ovaries of
      the bacteria-treated gilts were more intensely stained for NADPH-d than those in
      control animals. After bacteria administration, the intensity of NADPH-d reaction
      in all the structures of both ovaries in group II was higher than in control
      group. The strongest immunostaining for iNOS was observed in all structures of
      the bacteria-infused ovary. In the contralateral ovary, iNOS-immunoreactivity was
      weaker but still stronger than that in control group. The present results
      revealed that infusions of bacteria into the hilus of one ovary enhanced the
      activity of NADPH-d and immunoreactivity for iNOS in both porcine ovaries.
      However, the activity of both enzymes was higher in the bacteria-infused ovary
      than in the contralateral one. These data suggest that locally synthesized NO can
      mediate an inflammatory effect of bacteria in the porcine ovaries.

PMID- 14666164
TI  - Clinical importance of vascular LH/hCG receptors--a review.
AB  - It was believed for a long time that functional LH/hCG receptors were present
      only in gonads. Recent studies have demonstrated, however, that these receptors
      are also present in several nongonadal organs in the human body. Uterus is one of
      them. Besides two uterine layers, endothelial cells and smooth muscle of blood
      vessels in the uterus also contain these receptors. In vivo administration of hCG
      decreased vascular resistance in the human uterus and in vitro treatment
      increased vasodilatory and decreased vasoconstrictive eicosanoids in the vessels.
      These findings led us to investigate whether hCG administration to patients with
      signs of threatened abortion has any beneficial effect. Patients were treated
      with either magnesium or progesterone and/or hCG. The results showed that the
      frequency of patients reaching second trimester was higher when hCG was used,
      which was paralleled by a significant decrease in uterine vascular resistance.
      Patients who reached term after treatment had decreased incidence of preterm
      delivery and intrauterine growth retardation. In conclusion, we suggest that
      uterine vascular LH/hCG receptors play an important role in the peri-implantation
      period by increasing uterine blood flow through vasodilatation and also perhaps
      through angiogenesis and trophoblast invasion, resulting in therapeutic benefit.

PMID- 14666166
TI  - Involvement of gonadotropins in induction of luteolysis in pigs.
AB  - In our previous study we have demonstrated that treatment of endometrial explants
      with LH increased 13,14-dihydro-15-ketoprostaglandin F(2alpha) (PGFM)
      accumulation in pigs. This was particularly visible on Days 14-16 of the estrous
      cycle. Action of gonadotropin in porcine endometrium appears to be mediated by
      LH/hCG receptors whose number is dependent on the day of the estrous cycle. In
      the current study i.v. infusion (1 hour) of hCG (200 IU) performed on Days 10
      (n=4) and 12-14 (n=4) of the porcine estrous cycle did not affect plasma PGFM
      (ng/ml+/-SEM) concentrations. In contrast, administration of hCG on Days 15-17
      produced, depending on plasma PGFM level before the infusion period, three
      different types of response: I. plasma PGFM surge of amplitude 0.62+/-0.15 was
      observed when the mean basal pre-infusion PGFM plasma level was 0.23+/-0.05 (n=6
      gilts); II. the delayed PGFM surge of amplitude 0.62+/-0.15 was determined when
      basal pre-infusion PGFM level was 0.80+/-0.20 (n=6); and III. lack of PGFM
      response to hCG was found when basal pre-infusion PGFM level was 1.09+/-0.61
      (n=6). Concentrations of plasma PGFM before and after saline infusion did not
      differ on Days 12-14 and 16 of the estrous cycle. In the next experiment blood
      samples were collected every 1 hour on Days 12-19 of the estrous cycle to
      determine concentrations of LH, PGFM and progesterone in four gilts. In
      particular gilts, plasma peaks of LH closely preceded surges of PGFM in 72.7,
      84.6, 75.0 and 66.6 percent, respectively. The highest PGFM surges followed a
      decline in plasma progesterone concentration. We conclude that the increased
      PGF(2alpha) metabolite production after hCG infusion during the late luteal phase
      of the estrous cycle as well as the relationship between plasma LH and PGFM peaks
      suggest the LH involvement in the elevation of endometrial PGF(2alpha) secretion
      in pigs, and, in consequence, induction of luteolysis.

PMID- 14666165
TI  - Expression of functional luteinizing hormone (LH) receptor and its messenger
      ribonucleic acid in bovine endometrium: LH augmentation of cAMP and inositol
      phosphate in vitro and human chorionic gonadotropin (hCG) augmentation of
      peripheral prostaglandin in vivo.
AB  - Bovine endometrium contains LH/hCG binding sites and LH increases endometrial
      production of prostaglandin H synthase-2 (PGHS-2) and prostaglandin synthesis.
      This study showed that uterine endometrium contained both LH receptor mRNA
      transcript and a 93-kDa immunoreactive protein that bound to anti-rat LH receptor
      antibody. LH receptor and its mRNA were expressed maximally in the endometrium of
      cows from the luteal phase compared to the follicular phase of the estrous cycle.
      Furthermore, there was a response shown when incubation of endometrial minces
      from both pre-estrus/estrus and luteal phase (but not post-ovulatory phase) with
      LH or oxytocin (20 ng/ml) that resulted in a significant (p<0.02) increase in
      cAMP and total inositol phosphates. When Day 15 cows were injected i.v. with 3000
      units hCG, the increase in peripheral 13,14-dihydro-15-keto PGF(2alpha) was 2.5
      fold higher than saline controls or oxytocin. We conclude that LH stimulates
      endometrial cAMP and total inositol phosphates which results in increased
      formation of uterine PGHS-2 similar to LH effect on ovarian PGHS-2. The increased
      13,14-dihydro-15-keto PGF(2alpha) production induced in vivo by injections of hCG
      indicates that LH may have a reinforcing role in luteolysis.

PMID- 14666167
TI  - The influence of gabaergic drugs upon LH secretion from the pituitary of the
      common carp: an in vitro study.
AB  - In the present study, the perifusions of whole pituitary glands of spermiating
      male common carp were performed in the presence of several GABAergic drugs.
      Muscimol (agonist of GABA(A) receptors) and bicuculline (the antagonist of the
      same type of GABA receptors) did not modify basal LH release. LH basal secretion
      was not modified when pituitaries were perifused with baclofen--an agonist of
      GABAB receptors. On the other hand, baclofen at doses of 10(-8) and 10(-4) M
      significantly decreased GnRH-A-induced LH release to about 86% and 88% of LH
      levels in control group, respectively. In our previous study we have shown that
      GABA decreased basal and GnRH-A-stimulated in vivo and in vitro LH release. In
      conclusion, it can be suggested that in the mature male carp GABA exerts an
      inhibitory influence on GnRH-stimulated LH release, probably through the
      inhibition of the GnRH action on gonadotropes. This inhibition seems to be
      mediated by the B type of GABA receptors.

PMID- 14666168
TI  - Luteotrophic action of prolactin during the early luteal phase in pigs: the
      involvement of protein kinases and phosphatases.
AB  - Prolactin (PRL) involvement in the regulation of luteal steroidogenesis in pigs
      during the early luteal phase and pregnancy is well documented. The intracellular
      mechanism of PRL action in steroidogenic cells, however, is not fully recognized
      yet. In the current study, we have tested the hypothesis that protein kinase C
      (PKC) and tyrosine kinases (PTK) as well as serine-threonine (PP) and tyrosine
      phosphatases (PTP) are involved in PRL signaling in luteal cells originated from
      the early corpora lutea (CL) of cyclic sows. Luteal cells (50 000 cells/ml M199)
      were incubated for 8 h (37 degrees C) with PRL (200 ng) and low density
      lipoproteins (LDL) to stimulate P(4) production. In addition, treatments
      included: PKC inhibitors--staurosporine and chelerythrine chloride; tyrosine
      kinase inhibitors--genistein and tyrphostin; serine-threonine phosphatase
      inhibitors--okadaic acid, cantharidin (inhibitors of PP1/2A) and cypermethrin
      (inhibitor of PP2B); and tyrosine phosphatase inhibitor--sodium orthovanadate.
      Moreover, after incubation (37 degrees C) with PRL (200 ng) for 2, 5, 10 or 20
      min, luteal cells were homogenized and cytosolic as well as membrane fractions
      have been obtained. This was followed by partial purification of the subcellular
      fractions by DEAE-cellulose chromatography and determination of PKC activity by
      measuring the transfer of (32)P from [gamma-(32)P]ATP to histone III-S. In
      unstimulated porcine luteal cells the major proportion of PKC activity was
      present in the cytosol. Incubation of luteal cells with PRL resulted in a rapid,
      time dependent increase in the amount of PKC activity in the membrane fraction
      and a decrease in the amount of PKC activity in the cytosol fraction. PKC
      activity in the membrane fraction was maximal after 5 min of exposure the cells
      to PRL. Inhibitors of PKC and PTK suppressed PRL and LDL-induced P(4) production
      by porcine luteal cells. It is of interest that stimulated P(4) production was
      also reduced by inhibitors of PTP and PP1/2A (okadaic acid, cantharidin). In
      contrast, cypermethrin did not affect P(4) production stimulated by PRL and LDL.
      The results of the current study support the hypothesis that PKC and tyrosine
      kinases are intracellular mediators of PRL action in porcine luteal cells during
      the first days of the estrous cycle. The involvement of protein phosphatases in
      transmission of the PRL signal in early luteal cells in pigs is also suggested.

PMID- 14666169
TI  - Endometrial receptivity: expression of alpha3beta1, alpha4beta1 and alphaVbeta1
      endometrial integrins in women with impaired fertility.
AB  - Advances in immunohistochemical methods with the specificity of poly- and
      monoclonal antibodies allow the description of the endometrial receptivity, which
      is characterized by the ability of secretion of phase specific proteins and
      glikoproteins by epithelial and stromal cells. We studied the differences in the
      expression of alpha3beta1, alpha4beta1 and alphaVbeta1 integrins in endometrium
      of women with recurrent miscarriages and women with unexplained infertility. The
      endometrial tissue was collected during hysteroscopy performed between 7th and
      9th day after ovulation. The immunohistochemical evaluation of alpha3beta1,
      alpha4beta1 and alphaVbeta1 integrin expression was determined in all endometrial
      biopsies. Staining intensity of alpha3beta1 in glandular epithelium and
      endometrial stroma was similar in both groups. In women with recurrent
      miscarriages we noted a lower concentrations of the alpha4beta1 and alphaVbeta1
      integrins during the midluteal phase than in women with unexplained infertility.
      Moreover, integrins alpha4beta1 and alphaVbeta1 were expressed more frequently in
      glandular epithelium and endometrial stroma of women with unexplained infertility
      than those of women with recurrent miscarriages. However, alphaV(2)1 staining in
      endometrial stroma was stronger than that of alpha4beta1. It can be concluded,
      that these integrins may play an important role in the implantation process.

PMID- 14666170
TI  - Adrenocortical tumorigenesis in transgenic mice: the role of luteinizing hormone
      receptor and transcription factors GATA-4 and GATA-61.
AB  - Transgenic (TG) mice, bearing the Simian Virus 40 T-antigen (Tag) under a 6-kb
      fragment of the murine inhibin alpha-subunit promoter (inhalpha), develop gonadal
      tumors of granulosa or Leydig cell origin with 100% penetrance by the age of 5-7
      months. When these TG mice were gonadectomized prepubertally, between 21-25 days
      of life, adrenal gland tumors were observed in each mouse by the age of 5-7
      months. No adrenal tumors were detected in any intact TG, gonadectomized or
      intact or control non-TG littermates. The adrenocortical tumors appeared to
      originate from the X-zone of the adrenal cortex. If functional gonadectomy was
      induced by GnRH antagonist treatment or by cross-breeding of the TG mice into
      hypogonadotropic hpg genetic background, neither gonadal nor adrenal
      tumorigenesis appeared. This prompted a hypothesis that adrenal tumor development
      in inhalpha/Tag TG mice is related to elevated gonadotropin secretion, which is
      the most obvious difference between the surgical and functional gonadectomy
      models. The adrenal tumors and a cell line (Calpha1) derived from them, was found
      to express luteinizing hormone receptor (LHR), but no FSHR, and hCG treatment
      stimulated their proliferation. No FSHR was found in the adrenal glands. On the
      basis of this it was suggested that expression of the potent oncogene T-antigen,
      allow LH in adrenocortical cells to function as a tumor promoter, and induction
      of high level functional LHR expression in adrenal tumors. Given the induction of
      expression and regulation of the GATA-4 and GATA-6 zinc finger family of
      transcription factors in the gonads by gonadotropins, it was in our interest to
      explore their expression in the adrenals. We utilized the inalpha/Tag TG mouse
      model and pathological human adrenal samples to explore the role of GATA-4 and
      GATA-6 in adrenocortical tumorigenesis. Abundant GATA-6 mRNA expression was found
      in normal control adrenal cortex during mouse development, whereas GATA-4 mRNA
      was undetectable. In striking contrast to this, GATA-6 was absent from murine
      adrenocortical tumors, while GATA-4 mRNA expression was dramatically upregulated
      in the murine adrenal tumors as well as in human adrenocortical carcinomas. Taken
      together, these results suggest different roles for GATA-4 and GATA-6 in the
      adrenal gland, and implicate GATA-4 in adrenal LHR expression and tumorigenesis.
      Immunohistochemical detection of GATA-4 may serve as a useful marker in
      differential diagnosis of human adrenal tumors. In addition, the inhalpha/Tag TG
      model will be helpful for exploring the molecular mechanisms underlying
      adrenocortical tumorigenesis, ectopic LHR expression in adrenals and the GATA
      4/LHR interaction that is related to adrenal tumorigenesis in TG mice.

PMID- 14666171
TI  - Molecular aspects of direct LH/hCG effects on human endometrium--lessons from
      intrauterine microdialysis in the human female in vivo.
AB  - The regulation of human implantation is still unknown. Evidence derived from
      experiments in vitro and from animal systems suggest a direct impact of the
      embryo on endometrial differentiation and the implantation process itself. Being
      one of the earliest embryonic products, hCG may be a key mediator of this embryo
      maternal communication. Using a multiplex nested rT-PCR approach we have been
      able to demonstrate the presence of full-length and truncated hCG/LH-receptor
      mRNA in human endometrium and in decidua. The expression of functional receptors
      appears to be cycle-dependent and regulated by changes in the alternative
      splicing pattern. To investigate possible direct effects of hCG on endometrial
      paracrinology in the human female in vivo, we have developed an intrauterine
      microdialysis system that allows the continuous sampling from the uterine cavity
      over several hours as well as the application of exogenous hCG and the monitoring
      of the tissue response to this stimulus. HCG administration during the secretory
      phase significantly modulated several endometrial paracrine parameters that
      correlate to endometrial differentiation (IGFBP-1), angiogenesis (VEGF),
      implantation (LIF, M-CSF) and tissue remodelling (MMP-9). In summary,
      intrauterine microdialysis is a novel tool for the clinical assessment of
      endometrial paracrinology in vivo. HCG appears to directly modulate endometrial
      differentiation and function in humans.

PMID- 14666172
TI  - Targeted destruction of prostate cancer cells and xenografts by lytic peptide
      betaLH conjugates.
AB  - In series of experiments conducted in vitro, we have established the concept that
      conjugates of the lytic peptides Hecate or Phor14 with a fragment of the beta
      chain of LH (amino acids 80-94) selectively destroy both androgen sensitive and
      insensitive human prostate cancer cells. Extraction of steroids from the culture
      medium by charcoal reduced the ability of the conjugates to kill LNCaP, BRF41T
      and PC-3 cells. Addition of hormones known to up-regulate LH receptors
      (estradiol, testosterone or FSH) to the culture medium restored the ability of
      the conjugates to kill these cell lines. The toxicity of the conjugates (EC(50))
      to these cell lines was closely correlated to their LH binding capacities (f
      mol/10(6) cells). In series of in vivo experiments we have shown that both the
      Hecate and Phor14-betaLH conjugates are remarkably effective in causing tumor
      cell necrosis and cessation of tumor growth in nude athymic mice. Treatment with
      Hecate-betaLH (12 mg/kg body weight) resulted in a reduction of tumor burden (mg
      tumor/g body weight) from 60 to 14 (P<0.0001); treatment with Phor14-betaLH (12
      mg/kg body weight) reduced tumor burden to 27 mg (P<0.0001). Treatment with a
      high dose of Phor14-betaLH (24 mg/kg body weight) reduced the tumor burden from
      60 to 12 mg/kg P<0.0001). Pretreatment of animals receiving a low dose of Phor14
      betaLH (12 mg/kg) with either estradiol or follicle stimulating hormone, (FSH)
      resulted in reduction of tumor burden from 60 to 11 mg/kg. Administration of a
      second 3-week treatment after a one month recovery period caused complete
      regression of more than 75 percent of the tumors. No changes in body weight or
      histological abnormalities were found in any of the organs examined, except the
      testes.

PMID- 14666173
TI  - Different action of ovine GH on porcine theca and granulosa cells proliferation
      and insulin-like growth factors I- and II-stimulated estradiol production.
AB  - Growth hormone (GH) and insulin-like growth factors (IGFs) are recognized as
      regulators of ovarian function. This study was designed to compare the effect of
      GH and IGFs added alone or together on porcine theca interna and granulosa cells
      proliferation and steroidogenesis. Moreover, the effect of GH on IGF-I secretion
      was examined. Cells were isolated from medium size follicles and cultured in
      vitro for 48 h in serum free medium. Estradiol and IGF-I medium concentrations
      were determined by radioimmunoassays. Proliferation was evaluated by alamar blue
      assay and by radiolabelled thymidine incorporation. GH increased IGF secretion by
      granulosa cells while decreased its secretion by theca cells. Proliferation of
      both cell types was stimulated by IGF-I and IGF-II (30 ng/ml) and modestly
      inhibited by GH (100 ng/ml). Insulin-like growth factor II increased, in a
      statistically significant manner, estradiol secretion by both cell types, while
      IGF-I stimulated estradiol secretion to a greater extent by granulosa then by
      theca cells. The synergistic action of GH and IGFs on estradiol secretion was
      stimulatory in theca cells and inhibitory in granulosa cells. These data
      demonstrate that despite its direct action on estradiol secretion by granulosa
      and theca cells, GH also modulated estradiol secretion induced by IGFs.
      Differences in the estradiol production in response to GH alone and the effect of
      the synergistic action of GH and IGFs suggest that different cellular mechanisms
      for these hormones are triggered in each cell type.

PMID- 14666174
TI  - Changes in follicular fluid concentrations of steroids, the pattern of steroid
      secretion and aromatization capability of incubated preovulatory follicular wall
      of rats.
AB  - Female Wistar rats exhibiting a regular 4-day oestrous cycle were included in
      this study. They were killed on the day of pro-oestrus at 11.00, 14.00, 16.00,
      2.00, 22.00 and 24.00 h. The isolated preovulatory follicles were placed
      individually on a small triple disc of filter paper. They were cut in half and
      the flowing out follicular fluid (FF) was allowed to soak into the underlying
      filter paper disc, which was subsequently placed at the bottom of incubation
      chamber. It was rinsed with the incubation medium and this medium, containing FF,
      was collected. The remaining follicular wall was incubated for 3h. Some of the
      incubation media were supplemented with testosterone (T). The steroid content was
      estimated by radioimmunoassay. The secretion of estradiol (E) by follicular wall
      was high until 20.00 h while that of androgens until 22.00 h, and both declined
      thereafter. Relatively low progesterone (P) release rose sharply at 22.00 h and
      this hormone became the main steroid secreted at 24.00 h. The addition of T
      always enhanced the release of estradiol. Follicular fluid contained very little
      estradiol, while prevailing steroids were androgens. Decrease of androgen
      concentrations was found only at 24.00 h. Progesterone level, much lower than
      that of androgens, started to rise at 20.00 h and P was the main steroid present
      in FF at 24.00 h. The present results suggest an existence of selective passage
      of steroids into FF and show a presence of androgenic milieu surrounding cumulus
      oophorus in preovulatory FF. The results also indicate that the aromatase
      activity is sustained until ovulation and stress the role of the P rise observed
      in the secretion rate of follicular wall and FF content just before ovulation.

PMID- 14666175
TI  - Cytochrome P450 aromatase in the testis of immature and mature pigs.
AB  - Aromatization of androgens into estrogens is performed by a microsomal enzyme,
      the cytochrome P450 aromatase. A direct approach for identifying the cellular
      source of aromatase is the use of immunohistochemistry with a specific antibody
      that recognizes aromatase. The pig presents some unusual features with regard to
      the synthesis of testosterone and estrogens in the male gonads. In testes from
      prepubertal males, testosterone level measured radioimmunologically, was lower
      than in testes from adult pig, while estrogen secretion was relatively high and
      comparable to that of mature porcine gonads. Immunolocalization of aromatase in
      testes from both immature and mature pigs was confined to the Leydig cell
      cytoplasm. The intensity of immunohistochemical staining indicated the presence
      of unsynchronous Leydig cell population. Other somatic cells and germ cells were
      negative for aromatase. In control tissue sections, incubated in the absence of
      the primary antibody or in the presence of normal rabbit serum, no positive
      staining was observed. Western blot analysis revealed one major band of aromatase
      about 50-52 kDa in testes from both immature and mature pigs.

PMID- 14666176
TI  - Steroidogenic characteristics of in vitro cultured epididymal epithelial cells of
      the rat.
AB  - The paper presents the steroidogenic features of cultured epithelial cells of rat
      epididymis and their ability to synthesize steroid hormones. The cytoplasm of
      epididymal epithelial cells accumulated lipid droplets and contained active
      enzymes of steroidogenesis. Numerous mitochondria with lamellar cristae occurred
      near lipid droplets. Frequently, mitochondria formed a direct contact with lipid
      droplets and smooth endoplasmic reticulum. The hormone assay showed that the
      epididymal epithelial cells cultured without dihydrotestosterone synthesized and
      released the following steroids: dehydroepiandrosterone (DHEA), testosterone (T)
      and 17beta-estradiol (E). The levels of DHEA and T were very low. The
      concentration of E detected in media of cultured epididymal epithelial cells
      exceeded many times the concentration of E in control media. The cytoplasmic
      presence of organelles and enzymes that participated in the steroid synthesis
      indicated their similarity to steroidogenic cells. Epididymal epithelial cells
      were capable of moderate in vitro synthesis of androgens. It cannot be excluded
      that steroidogenesis in the cultured epididymal epithelial cells is maintained to
      sustain 17beta-estradiol synthesis pathways.

PMID- 14666177
TI  - Role of relative changes in caval flows for evaluation of right atrial pressure
      shifts induced by nitroglycerin.
AB  - Experiments on cats treated with nitroglycerin showed dynamic relationship
      between changes in caval venous flows: blood flow increased in the superior vena
      cava and decreased in the inferior vena cava. Blood pressure in the right atrium
      either decreased, or increased. No significant changes in total venous return
      were observed during maximum shifts in right atrial pressure, while contractility
      of the right ventricular myocardium usually decreased. Our findings suggest that
      the direction of the right atrial pressure shifts induced by nitroglycerin does
      not depend on venous return, but is determined by the prevalence of flow changes
      in the superior vena cava or inferior vena cava.

PMID- 14666178
TI  - Effect of chronic haloperidol on electrical parameters of command neurons in
      Helix Lucorum.
AB  - We studied the effects of neuroleptic haloperidol on electric characteristics
      (resting potential, action potential threshold, and critical level of
      depolarization) of command neurons LPa3, RPa3, LPa2, and RPa2 responsible for
      defense behavior in edible snail Helix Lucorum. Chronic administration of
      haloperidol led to hyperpolarization shift of the membrane potential and
      increased the threshold of action potential in these neurons. The data indicate a
      new possible mechanism of sedative action of neuroleptics based on
      hyperpolarization of some cerebral neurons, in particular, neurons responsible
      for some behavioral functions.

PMID- 14666179
TI  - Role of stomach regions and duodenum in the formation of electrical activity of
      gastroduodenal complex.
AB  - Functional activity of components of the gastroduodenal complex (gastric cardia,
      gastric corpus, pylorus, and duodenal bulb) was studied in 4 series of acute
      experiments. One of these regions was subjected to electrical stimulation in each
      series. Our results suggest that the cardia possesses rhythm-forming properties,
      the corpus plays a system-organizing role, the pylorus plays a trigger role, and
      the duodenal bulb produce synchronizing effects.

PMID- 14666180
TI  - Changes in blood cytochemical indexes in animals during pregnancy and after
      labor.
AB  - Intraleukocytic microbicidal activity of blood neutrophilic granulocytes in cows
      increased with increasing the term of pregnancy, decreased over the first 2 days
      after labor, and increased again in the follow-up period. Activity of
      microbicidal systems markedly decreased after labor, especially in the winter
      spring period.

PMID- 14666181
TI  - Detection and description of various stores of nitric oxide store in vascular
      wall.
AB  - We analyzed the possibility of the existence of various NO pools in the vascular
      wall. Incubation of isolated rat aorta with dinitrosyl iron complex (NO donor)
      led to the formation of NO stores in the vascular wall detected by vascular
      relaxation response induced by diethyldithiocarbamate and N-acetylcysteine.
      Comparison of the effects of successive application of diethyldithiocarbamate and
      N-acetylcysteine revealed two NO pools (one pool responded to both agents, while
      other responded only to N-acetylcysteine). Inhibition of guanylate cyclase with
      methylene blue abolished the response to diethyldithiocarbamate, while the
      reaction to N-acetylcysteine decreased by the value, corresponding to
      diethyldithiocarbamate-dependent relaxation. It is hypothesized that in the
      vascular wall NO is stored in the form protein-bound dinitrosyl iron complexes
      and S-nitrosothiols in hydrophilic and hydrophobic cell compartments.

PMID- 14666182
TI  - Effect of beta-adrenoceptor blockade on cardiac activity in rats during postnatal
      ontogeny.
AB  - Electrical stimulation of the right stellate ganglion produces a positive
      chronotropic effect in 21-, 56-, and 100-day-old rats. The response of the heart
      rate to suprathreshold stimulation increased from the 21st to 100th day. By
      contrast, during beta-adrenoceptor blockade the heart rate response decreased.
      The data suggest that the role of beta-adrenoceptor in the regulation of cardiac
      chronotropic function increased with age.

PMID- 14666183
TI  - Effect of stress on variability of systemic hemodynamics in rats of various
      genetic strains.
AB  - Power spectral density of heart rate fluctuations in the range of 0.02-5.00 Hz in
      August rats was lower than in Wistar rats. Changes in mean blood pressure and
      heart rate during stress (15-min immobilization) were similar in animals of both
      strains. As differentiated from Wistar rats, power spectral density of
      fluctuations in August rats considerably decreased after stress. August rats were
      characterized by low spectral power at rest and high resistance to the
      arrhythmogenic effect of 10-min acute myocardial ischemia.

PMID- 14666184
TI  - Frequency-dependent effects of low-intensity ultrasound on activity of isolated
      heart.
AB  - The experiments with low-intensity ultrasound stimulation of isolated rat heart
      revealed frequency-dependent effects of ultrasound in a frequency range of 45-298
      kHz on cardiac activity.

PMID- 14666185
TI  - Neurological deficit and disturbances in higher nervous activity during modeling
      of perinatal hypoxic-ischemic damage to the central nervous system in rat pups.
AB  - Seven-day-old Wistar rat pups were subjected to unilateral occlusion of the
      common cerebral artery and maintained in oxygen-low atmosphere. Neurological and
      behavioral changes were monitored for 12 weeks. The survival rate of treated
      animals was 90%. Body weight gain in these rats was lower than in the control.
      Neurological deficit was maximum 1 week after treatment and slightly regressed by
      the 12th week. Locomotor activity in treated rats was higher than in controls.
      Administration of ketamine in subanesthetic doses caused permanent ipsilateral
      rotational asymmetry in animals. Spatial disorientation and cognitive deficit in
      rats with hypoxic-ischemic damage to the central nervous system were revealed in
      passive avoidance, Y-maze, and rotarod tests. The total area of the hemisphere
      decreased, while the area of the lateral cerebral ventricle increased at the side
      of occlusion over the first 4-5 weeks of postnatal development. The size of the
      ipsilateral hemisphere remained low in adult animals.

PMID- 14666186
TI  - Effect of monotherapy and combination therapy with richlocaine on tissue hypoxia
      and activity of keratinocyte detoxifying systems in ischemic skin flap.
AB  - Treatment with richlocaine alone and, especially, in combination with
      antihypoxant energostim decreased the total content of hydroxyproline in the
      ischemic skin flap on day 3 after excision. Combination therapy with richlocaine
      and energostim normalized the redox potential in the energy supply system,
      improved antioxidant protection, and promoted the recovery of a balance between
      various components in the antioxidant system. These changes were not accompanied
      enhanced production of malonic dialdehyde. Our results suggest that combination
      therapy with richlocaine and energostim maintains the adaptive reserves of
      detoxifying systems in keratinocytes and prevents endotoxemia. Richlocaine
      primarily stimulates glycolytic synthesis of ATP, activates nonmitochondrial
      antioxidant enzymes, and increases RNase activity in lysosomes.

PMID- 14666187
TI  - Elevation of corazol-induced seizure threshold after active immunization of mice
      of various genetic strains with glutamate-bovine serum albumin conjugate.
AB  - We studied the effect of active immunization with glutamate-bovine serum albumin
      conjugate on acute generalized epileptiform activity evoked by single
      administration of corazol. Antibodies to glutamate produced an antiepileptic
      effect and elevated the threshold for clonic seizures and tonic phase of lethal
      seizures. In BALB/c mice this effect was more pronounced than in C57BL/6 mice.

PMID- 14666188
TI  - Effect of richlocaine alone or in combination with energostim on the severity of
      endotoxemia and survival of the skin under conditions of reduced blood flow.
AB  - The local anesthetic richlocaine decreased the area of necrosis in the skin flap
      under conditions of reduced blood flow by 29.5%. Improved survival of skin flap
      after richlocaine treatment alleviated endogenous intoxication, reduced secondary
      inflammatory reaction, improved liver function, and normalized the ratio between
      vasoconstricting and vasodilating prostaglandins. This effect was most pronounced
      after combination therapy with richlocaine and direct-action antihypoxant
      energostim.

PMID- 14666189
TI  - Changes in regulation of oxidase activity of peripheral blood granulocytes in
      women with habitual abortions.
AB  - Generation of active oxygen forms by blood granulocytes was studied in women with
      a history of habitual abortions (2-3 spontaneous abortions in the first
      trimester, undeveloped pregnancies). The level of spontaneous luminol-dependent
      chemiluminescence of nonfractionated peripheral blood was increased in this
      patient population (study group) in comparison with women with normal
      reproductive function (reference group). The two groups differed by the level of
      activation of respiratory burst induced by opsonized zymosan and by activity of
      isolated granulocytes in response to chemotactic peptide N-formyl-methionyl
      leucyl-phenylalanine (1-50 microM). Differences in the effects of inhibitor of
      tyrosine protein kinases and protein phosphatases and inhibitor of mitogen
      activated proteinkinase p38 MAPK were detected. The results attest to
      predisposition to oxidative stress and poor cytotoxic functions of granulocytes
      in women with habitual abortions, which can be due to specific features of
      regulation of oxidase activity by tyrosine protein kinases and protein
      phosphatases and by p38 MAPK.

PMID- 14666190
TI  - Enzyme immunoassay of NSE and GFAP as the criterion of dynamic evaluation of the
      rat blood-brain barrier in perinatal hypoxic ischemic injury of the CNS.
AB  - Enzyme immunoassay of the serum neurospecific antigens (gliofibrillar acid
      protein and neurospecific enolase) was used for evaluation of the resistance of
      the blood-brain barrier in Wistar rats with perinatal hypoxia and ischemia of the
      CNS. Perinatal hypoxia and ischemia of the CNS was modeled by two methods:
      ligation of the common carotid artery in 7-day-old rats followed by 3.5-h hypoxic
      hypoxia or 15-min anoxic exposure of fetuses isolated via hysterectomy on day 21
      of gestation. Enzyme immunoassay of serum gliofibrillar acid protein and
      neurospecific enolase in control an experimental rat pups was carried out once a
      week during 3 months. In controls serum levels of gliofibrillar acid protein and
      neurospecific enolase virtually did not change during postnatal development,
      while in animals with cerebral hypoxia and ischemia induced in fetuses by both
      methods serum concentration of neurospecific enolase sharply increased 1 week
      after the injury and increased on weeks 6 and 10. The content of gliofibrillar
      acid protein was maximum on week 1 and later considerably varied, the peaks of
      its concentrations observed on weeks 3 and 8 preceded the increase in
      neurospecific enolase activity in peripheral blood.

PMID- 14666191
TI  - Reactions of immune system to immobilization stress in inbred mice of different
      strains.
AB  - Mice of different strains can be classified by the intensity of humoral immune
      reaction to thymus-dependent antigen as high, moderate, and low responders. High
      and moderate responders (CBA/CaLac, DBA/1, BALB/c) are characterized by high
      sensitivity of the productive phase of humoral immune response and phagocytic
      activity of macrophages to immobilization stress. In low responders (C57BL/6,
      CC57W) stress only slightly affected the productive phase of the humoral immune
      response, but activity of peritoneal macrophages decreased. These differences in
      the reactions of the immune system of inbred mice after immobilization stress
      reflect different reactions of the immune system to extreme factors.

PMID- 14666192
TI  - Typing of Mycobacterium tuberculosis strains resistant to rifampicin and
      isoniazid by molecular biological methods.
AB  - Mutations in the rpoB, katG, inhA, oxyR/ahpC genes in rifampicin- and isoniazid
      resistant M. tuberculosis strains isolated from residents of Moscow, Astrakhan',
      and Moldova Republic were studied by molecular biological methods (heteroduplex
      analysis, single strand conformational polymorphism, biochips). Twenty-five
      combinations of mutations were detected. Some differences in the type
      distribution of detected mutations were found. The use of biochips is the most
      perspective method for determining the type of mutation.

PMID- 14666193
TI  - Spectrum of mutations in BRCA1 gene in hereditary forms of breast and ovarian
      cancer in Russian families.
AB  - The 5382insC mutation predominated (94%) in the spectrum of detected mutations of
      BRCA1 gene. High incidence of this mutation in familial breast cancer detected
      for the first time attested to origination of 5382insC mutation from the European
      part of Russia. The percentage of families with mutations in BRCA1 gene and
      familial predisposition to ovarian cancer was significantly higher than in
      hereditary predisposition to breast cancer (p<0.007). These data suggest that
      clinical manifestation of the mutation depends on genotypical factors other than
      the position of this mutation in BRCA1 gene. The results prompt screening for
      hereditary predisposition to these diseases.

PMID- 14666194
TI  - Oxidative stress in HEp-2 human laryngeal carcinoma cells induced by combination
      of vitamins B12b and C.
AB  - Incubation of human laryngeal epidermoid carcinoma HEp-2 cells with
      hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) for 1 h initiated
      oxidative stress accompanied by damage to mitochondria and increase in
      intracellular oxidative activity. Studies of the kinetics of these processes
      showed that the increase in intracellular H2O2 activity and mitochondrial damage
      are more likely a result, but not the cause of cell apoptosis during the first
      hour of their incubation with vitamins B12b and C.

PMID- 14666195
TI  - Study of total lipid peroxidation and antioxidant activity in pulmonary and
      mediastinal malignant and benign tumor tissue.
AB  - Total lipid peroxidation and antioxidant activity were studied in pulmonary and
      mediastinal malignant and benign neoplasms. In malignant tumors total lipid
      peroxidation increased and antioxidant activity decreased; the intensity of these
      shifts depended on histological characteristics and degree of malignancy: the
      most pronounced changes were observed in thymoma and adenocarcinoma tissues and
      minimum changes were found in bronchoalveolar carcinoma tissue.

PMID- 14666196
TI  - Artificial aging of mice.
AB  - Clinical signs of aging verified by morphometrical analysis of brain tissue were
      observed in young mice 4 months after administration of brain extract from old
      mice (5 intraperitoneal injections).

PMID- 14666197
TI  - Effect of regulatory peptides on gene transcription.
AB  - Experimental studies of geroprotective activity of synthetic oligopeptides and
      conformational analysis of the tetrapeptide Epithalon allowed us to hypothesize
      that regulatory oligopeptides directly initiate transcription of genes for
      vitally important proteins. Sequences of nucleotide pairs that can serve as
      binding sites for tetrapeptide Epithalon were identified in the promoter regions
      of retinal genes F379, telomerase, and RNA polymerase II.

PMID- 14666198
TI  - Postinfarction remodeling of the heart: types of pathomorphological changes in
      the right ventricle.
AB  - New geometric characteristics of the right ventricle depended on the localization
      of macrofocal transmural scars in the left ventricle of postinfarction heart.
      Most pronounced changes in the right ventricle were observed during dilatational
      and hypertrophic remodeling of the heart. The increase and decrease in the volume
      were most frequently occurring and pathognomonic forms of pathomorphological
      changes in the right ventricle. Dilatational remodeling was accompanied by a
      decrease in the volume of the right ventricle. The increase in the volume of this
      ventricle was typical of hypertrophic remodeling. Pathological variability in the
      right ventricle underlies the development of severe disturbances in intracardiac
      hemodynamics, i.e., patho- and thanatogenesis of postinfarction heart.

PMID- 14666199
TI  - Morphological study of reparative processes in the gingiva during therapy of
      chronic periodontitis with energostim and application of orthopedic splinting
      constructions.
AB  - We studied morphological characteristics of the regenerative process in gingival
      tissues during therapy of chronic periodontitis. Energostim stimulated
      macrophageal reaction and promoted neoangiogenesis in the inflammatory
      infiltrate. It was not observed after traditional drug therapy. Energostim
      promoted vascularization in regenerating tissues, normalized the structure at a
      greater area of the lamina propria of the gingiva, and prevented fibrous and
      sclerotic changes. The volume of histiolymphocytic infiltrates in regenerating
      gingival tissues decreased after application of intradental splints.

PMID- 14666200
TI  - Degenerative changes and cell death in long-living homo- and heterotopic
      transplants from embryonic germ layers of rat neocortex.
AB  - Morphological study of allotransplants of rat embryonic neocortex 14-18 months
      after transplantation into the neocortex, lateral cerebral ventricle, and sciatic
      nerve of adult animals revealed death of nerve and glial cells in the delayed
      postoperation period independently on the site of transplantation. After
      heterotopic transplantation the count of degenerated neurons was 2 times higher
      that after homotopic transplantation. In heterotopic transplants a considerable
      number of grafted neurons underwent reversible and irreversible degenerative
      changes accompanied by their premature aging. Neuronal death is probably
      determined by insufficiency of trophic influence from afferent structures and
      target tissues. We hypothesized that antiapoptotic preparations can be used for
      prevention of transplanted cell death. It was also found that degeneration of
      neurons was associated with impaired vascularization of transplants and
      pronounced immune reaction of the recipient in late posttransplantation period.
      Transplantation of embryonic brain structures can serve as a model system in
      studies concerning involutive and pathological processes in the central nervous
      system and in the search for factors improving survival of neurons.

PMID- 14666201
TI  - Ultrastructural changes in smooth muscle cells of the small intestine in suckling
      rabbits with experimental cholera.
AB  - Ultrastructural study of the small intestine in suckling rabbits with
      experimental cholera revealed involvement of the inner and outer smooth muscle
      layers into the pathological process. Smooth muscle cells were characterized by
      vacuolar and fatty degeneration and focal colliquative necrosis. Apoptosis played
      little role in gastrointestinal motility disturbances. The presence of
      considerable amounts of fluid in intestinal loops reflects peristaltic
      dysfunction due to generalized damage to smooth muscle cells.

PMID- 14666202
TI  - Method for studying the processes maintaining equilibrium at rest standing.
AB  - According to current concepts, two processes are responsible for the maintenance
      of body equilibrium: shifts of the reference point caused by changes in the
      posture and stabilization of oscillations of the center of mass relative to this
      point. Exact changes in these processes occurring at various forms of locomotor
      disorders remain unclear. We proposed an original mathematical method allowing
      separate evaluation of these two processes responsible for the maintenance of
      body equilibrium.

PMID- 14666203
TI  - Colorimetric in vitro evaluation of T-cell cytotoxicity.
AB  - We propose a new colorimetric method for evaluation of specific T lymphocyte
      cytotoxicity based on the capacity of viable cells to incorporate alamar blue
      dye, an indicator of cell metabolic activity. This method is effective for highly
      specific strains of cytotoxic T lymphocytes and for primary T killers formed in
      vivo and constituting a small part of analyzed cell population. This test is a
      simple nonradioactive method for evaluating specific cellular cytotoxicity
      exhibiting sufficient sensitivity for evaluation of this parameter in the
      presence of effector cells.

PMID- 14666204
TI  - Challenges for the evaluation of scientific literature: peer review.

PMID- 14666205
TI  - Human T-cell Lymphotropic Virus types I and II (HTLV-I/II) in French Guiana:
      clinical and molecular epidemiology.
AB  - We review here the epidemiological studies performed by our group on human
      retrovirus HTLV-I and HTLV-II infections and the associated diseases in French
      Guiana since 1984. French Guiana is an overseas French administrative district
      located between Brazil and Surinam. Its population is characterized by a large
      variety of ethnic groups, including several populations of African origin and
      various populations of Amerindian origin. Several epidemiological studies of
      large samples of pregnant women and in remote villages showed that HTLV-I is
      highly endemic in this area but is restricted to groups of African origin,
      especially the Noir-Marrons. In this endemic population, the results of
      segregation analysis in a genetic epidemiological study were consistent with the
      presence of a dominant major gene predisposing to HTLV-I infection, especially in
      children. In contrast, HTLV-II infection appears to be rare in French Guiana,
      having been found in only a few individuals of Brazilian origin. From a molecular
      point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and
      Amerindians appear to originate from Africa, as they belong to the large
      cosmopolitan molecular subtype A.

PMID- 14666206
TI  - The Pelotas birth cohort study, Rio Grande do Sul, Brazil, 1982-2001.
AB  - Given the growing recognition of the importance of the life course approach for
      the determination of chronic diseases, birth cohort studies are becoming
      increasingly important. This paper describes the methods used in the 1982 Pelotas
      (Brazil) birth cohort study, one of the largest and longest studies of this type
      in developing countries. All 5,914 hospital births occurring in Pelotas in 1982
      (over 99% of all deliveries) were studied prospectively. The main stages of the
      study took place in 1983, 1984, 1986, 1995, 1997, 2000, and 2001. More than two
      thousand variables are available for each subject who participated in all stages
      of the study. Recent phases of the study included the examination of 2,250 males
      when presenting for the army recruitment exam in 2000, the study of a 27% sample
      of men and women in 2001 through household visits, and the study of over 400
      children born to the cohort women. Follow-up rates in the recent stages of the
      cohort were 78.9% for the army examination and 69.0% for the household visits.
      Ethnographic and oral health studies were conducted in sub-samples. Some recent
      results on blood pressure, adolescent pregnancy, and asthma are presented as
      examples of utilization of the data. Suggestions on lessons learned for other
      cohort studies are proposed.

PMID- 14666207
TI  - Prevalence of having a regular doctor, associated factors, and the effect on
      health services utilization: a population-based study in Southern Brazil.
AB  - In order to assess the prevalence of having a regular doctor, associated factors,
      and the effects on health services utilization, a cross-sectional study was
      performed in Rio Grande, Brazil, from January to May 2000. A total of 1,260
      individuals 15 years or over were interviewed. Adjusted prevalence ratios and 95%
      confidence intervals were calculated, using a Poisson regression model. Some 37%
      of the sample had a regular doctor. Adjusted analysis revealed a direct and
      linear association with income. Female gender, age, private health insurance
      coverage, and chronic health problems were also associated with the outcome.
      Having a regular physician was associated with a 51% increase in clinical breast
      examination and a 62% increase in cervical cancer screening during the previous
      year, as well as a 98% increase in prostate cancer screening in the previous year
      in men 40 years or over. The study concluded that the prevalence of having a
      regular doctor in Brazil is low and is directly associated with socioeconomic
      factors. Individuals with a regular physician tend to have better access to
      health services. The promotion of consultation with a regular doctor among the
      population may improve health care quality and health services access,
      particularly in the poorest groups.

PMID- 14666208
TI  - [Haemophilus influenzae type b: epidemiological situation in the State of Minas
      Gerais, Brazil, 1993-1997].
AB  - Among Haemophilus influenzae type b (Hib) invasive diseases, pneumonia and
      meningitis are the most relevant in public health due to their frequency and
      severity. From 1993 to 1997, there were 720 cases of Hib meningitis in Minas
      Gerais State, Brazil, representing the most frequent cause of bacterial
      meningitis in infants (< 1 year) and the second most frequent among all causes of
      meningitis. The total estimated cases of invasive Hib diseases thus appear to
      justify the recent inclusion of the vaccine in the basic immunization protocol.
      The vaccine's high cost reinforces the need for more precise monitoring of the
      etiological diagnosis of meningitis cases, representing one of the weaknesses in
      the prevailing epidemiological surveillance system.

PMID- 14666209
TI  - [Isoniazid and rifampicin resistance and prior treatment for tuberculosis].
AB  - A case-control study in Rio de Janeiro in 1994 included 552 patients with a
      positive culture for Mycobacterium tuberculosis and reported a 1.8% resistance
      rate to rifampicin and isoniazid. Prior treatment for tuberculosis (the exposure
      factor) was associated with resistance. The binomial proportion was used to test
      the hypothesis of no dependence between the observed associations based on prior
      exposure to the drugs. This test showed a greater than expected dependence
      between resistances to rifampicin and isoniazid.

PMID- 14666210
TI  - [Spatial distribution of leptospirosis in Rio Grande do Sul, Brazil: recovering
      the ecology of ecological studies].
AB  - Leptospirosis is an endemic disease in the State of Rio Grande do Sul, Brazil,
      and presents a broad diversity of exposure routes, reservoirs, etiological
      agents, and clinical features. The main objective of this work is to identify
      transmission areas and possible ecological components of leptospirosis
      transmission. This was accomplished through the aggregation of epidemiological
      data into spatial units that represent the State's socio-environmental diversity.
      The 1,274 confirmed leptospirosis cases that occurred in 2001 were georeferenced
      in the counties of residence. The county maps were overlaid on environmental
      units characterizing land use, altitude, and river basins. Incidence rates for
      each environmental class were calculated, along with their statistical
      significance, through GIS aggregation operations. The highest incidence rates
      were verified in coastal sedimentary areas with low altitude and predominantly
      agricultural land use. In these areas, most of the cases were associated with
      irrigated farming. The results suggest the existence of favorable ecological
      characteristics for leptospirosis transmission in places involving proliferation
      of peri-domiciliary rodents and intensive agricultural production. The article
      discusses the effects of data aggregation into environmental units, as well as
      strategies to control the endemic in the State.

PMID- 14666211
TI  - [Analisys of work-related accidents and incidents in an oil refinery in Rio de
      Janeiro].
AB  - Accidents in the chemical industry can have serious consequences for workers,
      communities, and the environment and are thus highly relevant to public health.
      This article is the result of an occupational surveillance project involving
      several public institutions. We analyze 800 work-related accidents that resulted
      in injuries, environmental damage, or loss of production in 1997 in an oil
      refinery located in Rio de Janeiro, Brazil. The methodology was based on
      managerial and organizational approaches to accident investigation, with the
      European Union reporting system as the reference. The results highlight various
      limitations in the process of reporting and investigating accidents, as well as a
      certain hierarchy of accidents, with more attention given to accidents involving
      loss of production and less to those resulting in injuries, particularly among
      outsourced workers.

PMID- 14666212
TI  - [An ecologic study on tuberculosis in a Cuban municipality].
AB  - An ecological study analyzes tuberculosis incidence in the municipality of
      Marianao, Havana City Province, Cuba. The study characterizes tuberculosis
      incidence, identifies spatial distribution patterns, and relates tuberculosis
      incidence rates to socioeconomic factors. The spatial units are the 29
      neighborhoods in the municipality of Marianao. A pattern of neighborhoods with
      high rates located in the central region of the municipality is identified.
      Incidence rates are directly (and significantly) related to the percentage of
      families presenting dysfunctional problems and the percentage of the population
      with certain levels of overcrowding and inversely related to population density,
      while not significantly associated with level of schooling or prevailing housing
      conditions.

PMID- 14666213
TI  - [Alternative care options for pregnancy in Jalisco, Mexico].
AB  - The mother's culture has been identified as a factor in the use of health
      services for prenatal care. Beliefs and practices concerning traditional and
      domestic medicine used by women during pregnancy can play a role in the decision
      to seek medical care. In a non-probabilistic sample of 3,250 women, alternative
      care during pregnancy and its relationship to satisfactory prenatal care was
      studied. To analyze the association, the prenatal care variable was divided into
      (a) satisfactory and (b) unsatisfactory, according to a list of official Mexican
      standards. The chi-square test and odds ratio were applied, with p < 0.05. The
      association of alternative care with unsatisfactory prenatal care was
      established. Psycho-prophylactic training for delivery acted as a protective
      factor. The culture of pregnant woman in Mexico comprises meaning and behaviors
      that mix concepts and prescriptive ideas concerning domestic, traditional, and
      academic medicine, varying according to the stage of pregnancy, and which may be
      used in exclusive or complementary fashion. This situation should be considered
      in health education programs.

PMID- 14666214
TI  - [The private vaccines market in Brazil: privatization of public health].
AB  - The main objective of this article is to analyze the vaccines market in Brazil,
      which is characterized as consisting of two segments with distinct practices and
      logics: the public segment, focused on supply within the Unified National Health
      System (SUS) and the private segment, organized around private clinics,
      physicians' offices, and similar private health facilities. The private vaccines
      market segment, studied here for the first time, is characterized in relation to
      the supply and demand structure. Historical aspects of its structure are
      analyzed, based on the creation of one of the first immunization clinics in the
      country. The attempt was to analyze this segment in relation to its economic
      dimensions (imports and sales), principal manufacturers, and products marketed.
      It economic size proved much greater than initially hypothesized. The figures
      allow one to view it as one of the main segments in the pharmaceutical industry
      in Brazil as measured by sales volume. One detects the penetration of a
      privatizing logic in a sphere that has always been essentially public, thereby
      introducing into the SUS a new space for disregarding the principles of equity
      and universality.

PMID- 14666215
TI  - [Evaluation of the effectiveness of the congenital syphilis elimination campaigns
      on reducing the perinatal morbidity and mortality: Rio de Janeiro, 1999-2000].
AB  - The growing incidence of congenital syphilis in Rio de Janeiro City led the City
      Health Department to organize the congenital syphilis Elimination Campaigns in
      1999 and 2000, in order to call attention to the matter and to qualify health
      care personnel in the management of the disease. The aim of this paper was to
      evaluate the effectiveness of the campaigns, following the pregnant women
      identified with syphilis through the well-established health information systems
      (SINASC   Live births, SIM   mortality and SINAN   National disease surveillance
      data system). It became evident that a significant reduction on perinatal
      morbidity and mortality was achieved on the group of children born to mothers
      exposed to the campaigns, pointing out that the antenatal routine practice wasn't
      able to deal with the matter. The low number of congenital syphilis cases found
      on the surveillance system denotes a huge under-reporting of the disease.

PMID- 14666216
TI  - [Social distribution of AIDS in Brazil, according to labor market participation,
      occupation and socioeconomic status of cases from 1987 to 1998].
AB  - The dynamics of the Brazilian AIDS epidemic was analyzed by occupation, taken as
      a proxy for individual socioeconomic status. The analysis comprised AIDS cases
      aged 20-49 and diagnosed in 1987-1998. The temporal trend in AIDS incidence rates
      was analyzed by sex, occupational category, and quintiles defined by a Brazilian
      scale for socioeconomic status (SES). The proportions of AIDS cases stratified by
      SES quintiles were analyzed by exposure category. Among men, incidence rates
      increased in the 1st time period in almost all occupational categories,
      decreasing among those classified as "non-manual" occupations during the 2nd
      period. Among females, an annual increment was observed from 1987 to 1998 in
      nearly all occupational strata. The highest relative increases were observed
      among the lowest SES scales for both sexes. The intravenous drug user (IDU)
      exposure category had the lowest socioeconomic status for both sexes, whereas the
      homo/bisexual category had the highest. The analysis highlighted a progressive
      change in the epidemic's social gradient during the period, with a faster spread
      among the lower socioeconomic strata.

PMID- 14666217
TI  - [Factors associated with non-participation in screening for cervical cancer in
      Southern Brazil].
AB  - Early detection of cervical cancer substantially increases the probability of
      cure. The aim of this study was to determine the prevalence and factors
      associated with non-participation in cervical cancer screening among women 15 to
      49 years of age in Rio Grande, Southern Brazil. A representative survey was
      carried out using a systematic sample based on a census tract. Trained
      interviewers used standard, individualized, household questionnaires to interview
      the women. Data analysis used logistic regression according to a previously
      determined hierarchical framework. Among 1,302 women interviewed, 57% had never
      had a Pap smear. The risk factors most closely associated with non-participation
      in screening were black or brown skin color, young age, low family income, low
      schooling, living alone, and first childbirth after 25 years of age. Coverage for
      early detection of cervical cancer was very low. In addition, women at high risk
      of developing cervical cancer were shown to have a significantly higher risk of
      non-participation in this type of screening.

PMID- 14666218
TI  - [Blood feeding sources and peridomiciliation of Lutzomyia longipalpis (Lutz &
      Neiva, 1912) (Psychodidae, Phlebotominae)].
AB  - A precipitin test was employed to study the alimentary tract content of Lutzomyia
      longipalpis in the intra- and peridomiciliary environments in the municipality of
      Raposa, Maranh o State, a transmission area for visceral leishmaniasis or kala
      azar. Out of 2,240 female sandflies captured, 547 (24.4%) had fed on vertebrate
      blood, with the following proportions: avian (87.9%); rodent (47.2%); human
      (42.4%); canine (27.6%); opossum (26.6%); and equine (22.5%). Based on a survey
      of 120 human dwellings, chickens were found to be the most common domestic
      animals in the peridomicile (28.3%), followed by dogs (21.7%), cats (17.5%),
      donkeys (13.3%), pigeons (7.5%), rabbits (3.3%), ducks (3.3%), and horses,
      mallards, and pigs (1.7% each). Synanthropic animals included opossums (39.3%),
      followed by rats (37.9%), bats (14.3%), raccoons (3.6%), foxes (2.1%), snakes
      (1.4%), and frogs (1.4%). The peridomiciliary presence of domestic and
      synanthropic animals as well as sandflies that had fed on human, opossum, and
      canid blood supports the hypothesis that kala azar transmission has been taking
      place in the anthropic environment in the municipality of Raposa.

PMID- 14666219
TI  - [Oral health on the public agenda: an analysis of Municipal Health Council
      records in cities from the 17th Regional Health Division in the State of Parana,
      Brazil].
AB  - The present study analyzes interventions pertaining to oral health recorded in
      the minutes of meetings held by 15 Municipal Health Councils in cities from the
      17th Regional Health Division of the State of Parana, Brazil. Document analysis
      was performed by identifying health themes, emphasizing categorization of issues
      related to interventions in oral health. The most frequently analyzed themes were
      records concerning the programming and organization of oral health services,
      followed by health budget issues. In 90 of the 591 minutes studied, 134 records
      pertaining to oral health interventions were identified. An analysis of the
      latter showed that oral health interventions involve reports of actions already
      implemented and lack the characteristics of proposals when analyzed from the
      health planning perspective. This study highlights the need for dentists to
      expand their representation in such forums in order to play a broader role in the
      planning process and support oral health as a basic citizen's right.

PMID- 14666220
TI  - [Comments on studies of industrial and non-industrial environments in Brazil: a
      comparative approach].
AB  - Air quality in industrial environments has been studied since the second half of
      the 20th century. Well-documented results show that exposure to chemical
      pollutants through their consumption, production, and storage can damage workers'
      health. New research focusing on non-industrial environments has shown unexpected
      correlations between air quality and health effects. Artificial ventilation
      systems have been related to health-related complaints and a high rate of
      absenteeism. Symptoms related to air quality in non-industrial environments are
      recognized by the World Health Organization and encompassed under the so-called
      sick building syndrome (SBS). In Brazil there are few studies comparing indoor
      air quality and health. The present study is intended to map the studies already
      conducted in Brazil in order to encourage further research in this area, due to
      its importance for public health.

PMID- 14666221
TI  - Fertility and reproductive history of sterilized and non-sterilized women in
      Campinas, Sao Paulo, Brazil.
AB  - This article compares sterilized and non-sterilized women in relation to socio
      demographic characteristics, reproductive history, and cohabitation status. Women
      from 30 to 49 years of age and residing in Campinas, Sao Paulo State, Brazil,
      were interviewed with a pre-tested and structured questionnaire: 236 women
      sterilized at least five years before the interview and 236 non-sterilized women.
      The sterilized women were significantly more likely to be married or cohabiting,
      to be younger when they began cohabiting, and to have been in the union longer
      than the non-sterilized women. They also began childbearing at an earlier age and
      had a history of more pregnancies and more live births than non-sterilized women.
      Factors associated with a history of 3 or more live births at the time of the
      interview were surgical sterilization, younger age at first childbirth, older age
      at the interview, recognition of fewer contraceptive methods, and lower per
      capita income. The article concludes that sterilization generally appears to be
      the consequence of higher fertility in a group of women who initiate childbearing
      early in life, although its role in preventing these women from having even
      larger families may also have a demographic impact.

PMID- 14666222
TI  - [Assisted treatment and tuberculosis cure and treatment dropout rates in the
      Guarani-Kaiwa Indian nation in the municipality of Dourados, Mato Grosso do Sul,
      Brazil].
AB  - In January 1998, home treatment regimens were launched in the municipality of
      Dourados, State of Mato Grosso do Sul, Brazil, and accompanied by indigenous
      health agents as a means of replacing the previous regimen, in which Guarani
      Kaiwa tuberculosis patients were systematically hospitalized for up to six months
      in the Porta da Esperan a Hospital. In order to verify whether this change in
      strategy had any effect on the cure and treatment dropout rates, a retrospective
      study was conducted on 594 patient records from January 1996 to December 1999.
      Patients were divided into two groups: Group I, treated by hospitalization (291
      cases) and Group II, treated as outpatients (303 cases). Group II patients showed
      a significant increase in the cure rate and a significant reduction in the
      treatment dropout rate. The study also showed a high tuberculosis prevalence rate
      in children (40%), subsequently reported to the competent health authorities and
      thus launching specific projects to deal with this epidemiological reality. Based
      on these results, it is recommended that the assisted treatment strategy be
      adopted for other Indian populations.

PMID- 14666223
TI  - [Living conditions and infant mortality: intra-urban differentials in Recife,
      Pernambuco State, Brazil].
AB  - The objective of this study was to show infant mortality differentials in
      different areas of Recife, analyzing the relationship between living conditions
      and mortality risk. An ecological study design compared infant mortality
      coefficients in 1995 with living conditions indicators obtained from the 1991
      National Demographic Census. Information on the 770 infant deaths and 27,965 live
      births were collected from death and birth certificates. Information on water
      supply, sanitation, garbage collection, literacy, schooling, income, and
      overcrowding were used to establish a compound indicator for living conditions,
      constructed through factor analysis. The neighborhoods were then ordered
      according to the level of living conditions and grouped in 4 clusters, through
      hierarchical cluster analysis. Infant, neonatal, and post-neonatal mortality
      coefficients were 23.94, 17.66, and 6.28, respectively, for cluster I; and 32.04,
      20.24, and 11.80 for cluster IV. In general, an inverse relationship was found
      between infant mortality and living conditions in clusters from Recife, revealing
      inequalities that are disguised when coefficients are expressed as averages for
      the entire city.

PMID- 14666224
TI  - [Cooperation and conflict in childbirth care: representations and practices of
      nurses and obstetricians].
AB  - In Brazil, where birthing generally occurs in hospitals and under the care of
      obstetricians, the incorporation of nurses is a strategy that has been used
      recently in an attempt to improve obstetric care. This study, conducted in two
      maternity hospitals in Rio de Janeiro, focuses on representations of
      obstetricians and nurses regarding teamwork and analyzes how the dimensions of
      power, cooperation/conflict, and technical autonomy are permeated by dualistic
      conceptions which influence the quality of health care for women during
      childbirth. On the one hand, the results show a consensus regarding the
      advantages of professional cooperation in the improvement of health care,
      assuming the existence of a clear definition of professional roles. At the same
      time, conflicts regarding therapeutic conduct during the birth process reflect
      the professionals' perceptions of autonomy and the influence of professional
      hierarchies, in which obstetric care is seen to depend on the "objective
      observation" of the women giving birth. The degree of conflict is differentiated
      according to the institutional context and related to dualistic conceptions such
      as objective/subjective, rational/emotional, and male/female.

PMID- 14666225
TI  - [Violent relationship in young people and STD/AIDS risk].
AB  - To verify whether affective relationships involving violence are associated with
      increased risk of sexually transmitted diseases (STDs), including AIDS, we
      conducted a survey among youth 14 to 22 years of age residing in two low-income
      communities in Rio de Janeiro, Brazil. We used a qualitative methodology with
      focal groups and individual interviews. Violence is part of the routine among
      these youth in both their community and families. The following factors were
      associated with violence in interpersonal relations: lack of money, unemployment,
      drug and alcohol use, jealousy, and infidelity. The young people reported that
      condom use is not negotiated with violent partners, resulting in increased risk
      of STD/AIDS. The results indicate that violence is multi-factorial, and when
      present in interpersonal relationships it intervenes negatively in relation to
      protection against STD/AIDS.

PMID- 14666226
TI  - [Overweight and obesity prevalences in male adolescents in Northeast Brazil, 1980
      2000].
AB  - This study aimed to determine the prevalence rates for overweight and obesity
      among male adolescents in the States of Northeast Brazil from 1980 to 2000, and
      to compare them over time to identify trends. The Brazilian Army database was
      used, with information on 316,925 adolescent conscripts. Overweight was defined
      as body mass index (BMI) from 25 to 29.9Kg/m  and obesity as BMI > 30Kg/m . An
      upward curve was identified, showing that the secular tendency in the last twenty
      years increased for both overweight and obesity. The upward trend in overweight
      and obesity prevalence rates was observed in all States of Northeast Brazil.
      Although lower prevalence rates were observed than in developed countries, the
      speed of increase is cause for concern.

PMID- 14666227
TI  - [Risks associated with the weaning process in children born in a university
      hospital: a prospective cohort in the first year of life, Sao Paulo, 1998-1999].
AB  - This study describes breastfeeding practices with children born in a university
      hospital in the city of S o Paulo, Brazil, and identifies factors associated with
      duration of breastfeeding and exclusive breastfeeding. A cohort of 506 children
      was identified; of these, it was possible to analyze information on feeding
      practices for 450 infants at least until the second month of life. Daily
      information on infant feeding was recorded by mothers in a food frequency
      questionnaire. Survival analysis techniques (Kaplan-Meier and Cox) were used.
      Median duration of breastfeeding and exclusive breastfeeding were 205 and 23
      days, respectively. The principal factors related to exclusive breastfeeding were
      mother's age (hr young/old = 1.22; 95% CI = 1.006-1.486) and mother's schooling
      (hr primary/university = 2.13; 95% CI = 1.381-3.307 and hr secondary/university =
      1.78; 95% CI = 1.145-2.792), which could be related to knowledge concerning the
      benefits of exclusive breastfeeding.

PMID- 14666228
TI  - [Food intake according to socioeconomic and demographic profile: the Bambui
      Project].
AB  - A nutritional survey was performed in a random sample of 546 individuals (ages 18
      and over) in a city named Bambui (15,000 inhabitants) in Minas Gerais State,
      Brazil, using the Semi-Quantitative Food Frequency Questionnaire (SFFQ). Median
      calorie intakes for women and men were 2,807 and 3,775kcal, respectively. Men
      consumed four times more alcohol than women, and women consumed more
      carbohydrates, fiber, and polyunsaturated fatty acids (PUFA). The relative
      consumption of proteins (15%), carbohydrates (57%), and lipids (28%) were
      adequate in both genders. The average proportions, for all participants, of an
      inadequate share of lipids, saturated fatty acids (SFA), PUFA, and cholesterol in
      the total calorie intake were, respectively, 36%, 90%, and 50%, and were more
      pronounced in men than in women. The lipid, SFA, and PUFA intake for women and
      the lipid and SFA intake for men increased with income. The PUFA/SFA ratio and
      the PUFA and dietary fiber intake were below the recommended levels in both
      genders. Dietary habits presented a differential inadequacy, suggesting possible
      population risk clusters for cardiovascular diseases.

PMID- 14666229
TI  - [Evaluative research on occupational rehabilitation: the effectiveness of a
      health care service subject to dismantlement].
AB  - This article deals with the results obtained from 1995 to 1997 by an innovative
      occupational rehabilitation model for individuals with repetitive strain
      injury/work related musculoskeletal disorder (RSI/WRMD), developed by the
      Campinas Occupational Rehabilitation Center under the Brazilian National
      Institute for Social Security. The study had two objectives: 1) to reconstruct
      the program as a precondition for evaluation and 2) to evaluate the model's
      effectiveness in reestablishing the autonomy of individuals with RSI/WRMD. The
      methodology involved document analysis in order to reconstruct the program's
      background in terms of problem identification, organizational participation,
      awareness-raising, staff characteristics and responsibilities, and profile of the
      clientele. An analysis of 221 patient files provided the basis for constructing
      an evaluative instrument consisting of different dimensions, variables, and
      indicators, which was applied to a sample of 47 patient histories prior and
      subsequent to rehabilitative intervention. High effectiveness was observed in the
      model, with variations in the different target dimensions.

PMID- 14666230
TI  - [Food intake in overweight and normal-weight adolescents in the city of Rio de
      Janeiro].
AB  - This article compares the food intake of overweight and normal-weight adolescents
      from 12 to 17.9 years of age (71.8% of the original sample). Data were obtained
      in a survey performed in the city of Rio de Janeiro, Brazil, in 1995-1996. Food
      intake was assessed by a semi-quantitative food frequency questionnaire, and
      nutritional status was assessed by body mass index (BMI = weight/stature ).
      Adolescents classified as overweight reached the 90th percentile of the 1989
      Brazilian BMI distribution. Food intake of overweight and non-overweight subjects
      was similar. Both groups showed below-minimum-recommended food-group intakes and
      higher intake of high-density food items. These nutritional habits are risk
      factors for obesity and chronic diseases later in life.

PMID- 14666231
TI  - [The occurrence and distribution of lymphatic filariasis in Greater Metropolitan
      Recife: the case of an endemic area in Jaboatao dos Guararapes, Pernambuco,
      Brazil].
AB  - This article analyzes the results of an epidemiological survey on the occurrence
      and distribution of lymphatic filariasis in Cavaleiro, a district in the city of
      Jaboatao dos Guararapes in Greater Metropolitan Recife, Pernambuco State, Brazil.
      The district was divided into 12 areas, and a cross-sectional technique was used
      to examine 9,520 individuals, of whom 2.2% were found to be infected. There were
      positive cases in 11 of the areas. The prevalence rate ranged from 0% to 5.15%.
      The majority (64.3%) of infected individuals were males (p < 0.05). Infected
      individuals were identified in all age groups. The results show that lymphatic
      filariasis is still an important public health problem in the Cavaleiro district
      and that it deserves attention by municipal authorities and health planners.

PMID- 14666232
TI  - Acceptability of emergency contraception in Brazil, Chile, and Mexico: 1 -
      Perceptions of emergency oral contraceptives.
AB  - This article presents the results of a study on the acceptability of emergency
      contraception (EC) in Brazil, Chile, and Mexico. Opinions of potential users and
      possible providers were obtained through discussion groups and those of
      authorities and policy-makers through semi-structured interviews. Most
      participants had a positive opinion of EC, based on the view that it can help
      reduce unplanned pregnancy, adolescent pregnancy, and unsafe abortion. Several
      interviewees felt that all women should be informed about EC, while others viewed
      it as a method for special situations such as rape and unprotected first sexual
      intercourse. Concern was expressed that its introduction might be associated with
      a decrease in condom use, increase in sexually transmitted diseases, and
      irresponsible or promiscuous sexual behavior among adolescents. The need for EC
      was clearly perceived by most participants, leading to the conclusion that health
      authorities have the responsibility of implementing programs for its
      introduction. Training of health care personnel should include the discussion of
      reproductive health problems that could be prevented by EC.

PMID- 14666233
TI  - [Fatal traffic accidents and their association with the infant mortality rate and
      adolescence].
AB  - This ecological study evaluates the association between fatality rates in traffic
      accidents (FR-V) and the study variables: infant mortality rate (IMR), proportion
      of young drivers involved in motor vehicle accidents (MVA) with casualties, and
      the proportion of young residents from 1995 to 1998 in the Brazilian State
      capitals and the Federal District. There was an important association between the
      MVA fatality rate and IMR (r = 0.57; p = 0.002), that is, the less developed a
      society, the higher its traffic mortality rate. No significant association was
      found between the proportion of young drivers in MVA with casualties and the MVA
      fatality rate (r = -0.27; p = 0.184). Nevertheless, the strong association
      observed between the proportion of young residents and the MVA mortality rate (r
      = 0.59; p = 0.002) suggests a possible correlation between traffic mortality and
      adolescence.

PMID- 14666234
TI  - [Pedagogical approaches and educational practices in health sciences].
AB  - Educational practices are widely used in the health field, both in continuing
      education for health professionals and health education for the general
      population. These two fields intersect through the development of educational
      knowledge oriented by a set of target representations of man and society. Such
      representations are demonstrated by teaching/learning processes in the four main
      pedagogical trends in Brazil: traditional, renewed, conditioning-based, and
      liberating (or the Paulo Freire approach). Based on their respective principles,
      methods, and individual and social consequences, we contend that liberating
      pedagogy can produce better results than the others by allowing the student's
      active participation in the learning process, thus fostering continuous
      development of human skills in both the health services clientele and health
      workers.

PMID- 14666235
TI  - [Ecoparasitoses and public health in Brazil: challenges for control].
AB  - Parasitic skin diseases such as scabies, pediculosis, tungiasis, and cutaneous
      larva migrans are hyperendemic in the numerous poor communities in Brazil and are
      commonly associated with considerable morbidity. However, programs to control
      ectoparasites are non-existent in the country's public health system. Due to
      neglect of these diseases by the population itself and health care professionals,
      the diseases' highly contagious characteristics, and lack of effective treatment
      and/or presence of animal reservoirs together with a complex life cycle,
      effective control of ectoparasites is an enormous public health challenge. This
      article discusses potential measures to control parasitic skin diseases in
      affected communities, based on mass treatment, health education, and (when
      applicable) eradication of animal reservoirs.

PMID- 14666236
TI  - [Asthma mortality in the Municipality of Sao Paulo (1993-1995): analysis by
      multiple cause of death].
AB  - This article aims to quantify the asthma mortality rate using the multiple
      causality analytical method in comparison to the underlying cause of death. Data
      were obtained from all death certificates (224,854) of individuals from 5 to 34
      years of age issued in 1993, 1994, and 1995 in the Municipality of S o Paulo, in
      which mention of the word asthma was considered valid information (code 493/ICD
      9). First, the underlying cause of death was studied. The same data were then
      used, but submitted to the multiple causality method. The comparative study of
      basic and multiple causes of death increased the diagnosis of asthma by a ratio
      of 1.165. The over-20-year age group remained the most affected by the problem.
      The age range of individuals most affected by this disease did not change with
      the analytical method (20 to 34 years). Although asthma was present more
      frequently when the multiple causality method was used, the increase in the
      number of asthma diagnoses highlights that the disease can be considered
      underreported in Brazil in the chain of events leading to death.

PMID- 14666237
TI  - [Monitoring of trace elements in oysters marketed in Recife, Pernambuco, Brazil].
AB  - Samples of oysters marketed in Recife, Pernambuco, Brazil, were monitored for the
      concentration of trace elements (Hg, Zn, Fe, Cu, and Mn) for one year (from March
      2001 to February 2002). Mercury was the principal contaminant found in oysters
      and the element posing the greatest public health risk. Mercury levels in oysters
      reached 551.12 g/kg (wet weight). These values suggest that oyster consumption
      should be restricted, especially among communities that gather them as a
      subsistence activity, as well as by children and pregnant women. Evaluation of
      mercury concentration in seafood is an important factor for assessing the risk of
      contamination among individuals who are not occupationally exposed.

PMID- 14666244
TI  - The use and misuse of the "impact factor" as a parameter for evaluation of
      scientific publication quality: a proposal to rationalize its application.
AB  - We present a critical analysis of the generalized use of the "impact factor". By
      means of the Kruskal-Wallis test, it was shown that it is not possible to compare
      distinct disciplines using the impact factor without adjustments. After assigning
      the median journal the value of one (1.000), the impact factor value for each
      journal was calculated by the rule of three. The adjusted values were
      homogeneous, thus permitting comparison among distinct disciplines.

PMID- 14666245
TI  - Neuroprotection by flavonoids.
AB  - The high morbidity, high socioeconomic costs and lack of specific treatments are
      key factors that define the relevance of brain pathology for human health and the
      importance of research on neuronal protective agents. Epidemiological studies
      have shown beneficial effects of flavonoids on arteriosclerosis-related pathology
      in general and neurodegeneration in particular. Flavonoids can protect the brain
      by their ability to modulate intracellular signals promoting cellular survival.
      Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin)
      showed a marked cytoprotective capacity in in vitro experimental conditions in
      models of predominantly apoptotic death such as that induced by medium
      concentrations (200  M) of H2O2 added to PC12 cells in culture. Nevertheless,
      quercetin did not protect substantia nigra neurons in vivo from an oxidative
      insult (6-hydroxydopamine), probably due to difficulties in crossing the blood
      brain barrier. On the other hand, treatment of permanent focal ischemia with a
      lecithin/quercetin preparation decreased lesion volume, showing that preparations
      that help to cross the blood-brain barrier may be critical for the expression of
      the effects of flavonoids on the brain. The hypothesis is advanced that a group
      of quercetin-related flavonoids could become lead molecules for the development
      of neuroprotective compounds with multitarget anti-ischemic effects.

PMID- 14666246
TI  - Characterization of  -trypsin at acid pH by differential scanning calorimetry.
AB  - Trypsin is a serino-protease with a polypeptide chain of 223 amino acid residues
      and contains six disulfide bridges. It is a globular protein with a predominance
      of antiparallel  -sheet and helix in its secondary structure and has two domains
      with similar structures. We assessed the stability of  -trypsin in the acid pH
      range using microcalorimetric (differential scanning calorimetry) techniques.
      Protein concentrations varied in the range of 0.05 to 2.30 mg/ml. Buffer
      solutions of 50.0 mM  -alanine and 20.0 mM CaCl2 at different pH values (from 2.0
      to 4.2) and concentrations of sorbitol (1.0 and 2.0 M), urea (0.5 M) or
      guanidinium hydrochloride (0.5 and 1.0 M) were used. The data suggest that we are
      studying the same conformational transition of the protein in all experimental
      situations using pH, sorbitol, urea and guanidinium hydrochloride as perturbing
      agents. The observed van't Hoff ratios (deltaHcal/deltaHvH) of 1.0 to 0.5 in the
      pH range of 3.2 to 4.2 suggest protein aggregation. In contrast,
      deltaHcal/deltaHvH ratios equal to one in the pH range of 2.0 to 3.2 suggest that
      the protein unfolds as a monomer. At pH 3.00,  -trypsin unfolded with Tm = 54 C
      and deltaH = 101.8 kcal/mol, and the change in heat capacity between the native
      and unfolded forms of the protein (deltaCp) was estimated to be 2.50   0.07 kcal
      mol-1 K-1. The stability of  -trypsin calculated at 298 K was deltaG D = 5.7
      kcal/mol at pH 3.00 and deltaG D = 15.2 kcal/mol at pH 7.00, values in the range
      expected for a small globular protein.

PMID- 14666247
TI  - Standard-curve competitive RT-PCR quantification of myogenic regulatory factors
      in chicken embryos.
AB  - The reverse transcription-polymerase chain reaction (RT-PCR) is the most
      sensitive method used to evaluate gene expression. Although many advances have
      been made since quantitative RT-PCR was first described, few reports deal with
      the mathematical bases of this technique. The aim of the present study was to
      develop and standardize a competitive PCR method using standard-curves to
      quantify transcripts of the myogenic regulatory factors MyoD, Myf-5, Myogenin and
      MRF4 in chicken embryos. Competitor cDNA molecules were constructed for each gene
      under study using deletion primers, which were designed to maintain the anchorage
      sites for the primers used to amplify target cDNAs. Standard-curves were prepared
      by co-amplification of different amounts of target cDNA with a constant amount of
      competitor. The content of specific mRNAs in embryo cDNAs was determined after
      PCR with a known amount of competitor and comparison to standard-curves.
      Transcripts of the housekeeping  -actin gene were measured to normalize the
      results. As predicted by the model, most of the standard-curves showed a slope
      close to 1, while intercepts varied depending on the relative efficiency of
      competitor amplification. The sensitivity of the RT-PCR method permitted the
      detection of as few as 60 MyoD/Myf-5 molecules per reaction but approximately 600
      molecules of MRF4/Myogenin mRNAS were necessary to produce a measurable signal. A
      coefficient of variation of 6 to 19% was estimated for the different genes
      analyzed (6 to 9 repetitions). The competitive RT-PCR assay described here is
      sensitive, precise and allows quantification of up to 9 transcripts from a single
      cDNA sample.

PMID- 14666248
TI  - The secondary alcohol and aglycone metabolites of doxorubicin alter metabolism of
      human erythrocytes.
AB  - Anthracyclines, a class of antitumor drugs widely used for the treatment of solid
      and hematological malignancies, cause a cumulative dose-dependent cardiac
      toxicity whose biochemical basis is unclear. Recent studies of the role of the
      metabolites of anthracyclines, i.e., the alcohol metabolite doxorubicinol and
      aglycone metabolites, have suggested new hypotheses about the mechanisms of
      anthracycline cardiotoxicity. In the present study, human red blood cells were
      used as a cell model. Exposure (1 h at 37 C) of intact human red blood cells to
      doxorubicinol (40  M) and to aglycone derivatives of doxorubicin (40  M) induced,
      compared with untreated red cells: i) a ~2-fold stimulation of the pentose
      phosphate pathway (PPP) and ii) a marked inhibition of the red cell antioxidant
      enzymes, glutathione peroxidase (~20%) and superoxide dismutase (~60%). In
      contrast to doxorubicin-derived metabolites, doxorubicin itself induced a
      slighter PPP stimulation (~35%) and this metabolic event was not associated with
      any alteration in glutathione reductase, glutathione peroxidase, catalase or
      superoxide dismutase activity. Furthermore, the interaction of hemoglobin with
      doxorubicin and its metabolites induced a significant increase (~22%) in oxygen
      affinity compared with hemoglobin incubated without drugs. On the basis of the
      results obtained in the present study, a new hypothesis, involving doxorubicinol
      and aglycone metabolites, has been proposed to clarify the mechanisms responsible
      for the doxorubicin-induced red blood cell toxicity.

PMID- 14666249
TI  - Age-related changes of the multidrug resistance P-glycoprotein function in normal
      human peripheral blood T lymphocytes.
AB  - The multidrug resistance P-glycoprotein is a transmembrane efflux pump expressed
      by lymphocytes and is involved in their cytolytic activity. In the present study,
      we investigated the age-related changes of P-glycoprotein function in normal
      peripheral blood lymphocytes. Blood samples from 90 normal volunteers (age range,
      0 to 86 years) were analyzed. P-glycoprotein function was assessed by the flow
      cytometric rhodamine 123 assay. P-glycoprotein function was highest in cord blood
      and progressively declined with age in peripheral blood T CD4+ and CD8+ cells. In
      contrast, P-glycoprotein function did not vary with age in CD19+ B or CD16+CD56+
      natural killer cells. These data suggest that the decline in P-glycoprotein
      function in T CD4+ and CD8+ lymphocytes as a function of age may contribute to
      the decrease in T cell cytolytic activity with aging.

PMID- 14666250
TI  - Eye color as an indicator of social rank in the fish Nile tilapia.
AB  - We investigated the association of eye color with the dominant-subordinate
      relationship in the fish Nile tilapia, Oreochromis niloticus. Eye color pattern
      was also examined in relation to the intensity of attacks. We paired 20 size
      matched fish (intruder: 73.69   11.49 g; resident: 75.42   8.83 g) and evaluated
      eye color and fights. These fish were isolated in individual aquaria for 10 days
      and then their eye color was measured 5 min before pairing (basal values). Twenty
      minutes after pairing, eye color and fights were quantified for 10 min. Clear
      establishment of social hierarchy was observed in 7 of 10 pairs of fish. Number
      of attacks ranged from 1 to 168 among pairs. The quartile was calculated for
      these data and the pairs were then divided into two classes: low-attack (1 to 111
      attacks - 2 lower quartiles) or high-attack (112 to 168 attacks - 2 higher
      quartiles). Dominance decreased the eye-darkening patterns of the fish after
      pairing, while subordinance increased darkening compared to dominance.
      Subordinate fish in low-attack confrontations presented a darker eye compared to
      dominant fish and to the basal condition. We also observed a paler eye pattern in
      dominants that shared low-attack interactions after pairing compared to the
      subordinates and within the group. However, we found no differences in the
      darkening pattern between dominants and subordinates from the high-attack groups.
      We conclude that eye color is associated with social rank in this species.
      Moreover, the association between eye color and social rank in the low-attack
      pairs may function to reduce aggression.

PMID- 14666251
TI  - The role of complement in the modulation by fluid-phase IgG of the production of
      reactive oxygen species by polymorphonuclear leukocytes stimulated with IgG
      immune complexes.
AB  - The production of reactive oxygen species (ROS) by polymorphonuclear leukocytes
      (PMN) can be induced by immune complexes and is an important component of
      phagocytosis in the killing of microorganisms, but can also be involved in
      inflammatory reactions when immune complexes are deposited in tissues. We have
      observed that fluid-phase IgG can inhibit the generation of ROS by rabbit PMN
      stimulated with precipitated immune complexes of IgG (ICIgG) in a dose-dependent
      manner, acting as a modulatory factor in the range of physiological IgG
      concentrations. This inhibitory effect is compatible with the known affinity (Kd)
      of monomeric IgG for the receptors involved (FcRII and FcRIII). The presence of
      complement components in the immune complexes results in a higher stimulation of
      ROS production. In this case, however, there is no inhibition by fluid-phase IgG.
      The effect of complement is strongly dependent on the presence of divalent
      cations (Ca2+ or Mg2+) in the medium, whereas the stimulation of ICIgG (without
      complement) does not depend on these cations. We have obtained some evidence
      indicating that iC3b should be the component involved in the effect of complement
      through interaction with the CR3 receptor. The absence of the inhibitory effect
      of fluid-phase IgG in ROS production when complement is present in the immune
      complex shows that complement may be important in vivo not only in the production
      of chemotactic factors for PMN, but also in the next phase of the process, i.e.,
      the generation of ROS.

PMID- 14666252
TI  - c-Fos expression induced by electroacupuncture at the Zusanli point in rats
      submitted to repeated immobilization.
AB  - In laboratory animals, acupuncture needs to be performed on either anesthetized
      or, if unanesthetized, restrained subjects. Both procedures up-regulate c-Fos
      expression in several areas of the central nervous system, representing therefore
      a major pitfall for the assessment of c-Fos expression induced by
      electroacupuncture. Thus, in order to reduce the effect of acute restraint we
      used a protocol of repeated restraint for the assessment of the brain areas
      activated by electroacupuncture in adult male Wistar rats weighing 180-230 g.
      Repeated immobilization protocols (6 days, 1 h/day and 13 days, 2 h/day) were
      used to reduce the effect of acute immobilization stress on the c-Fos expression
      induced by electroacupuncture at the Zusanli point (EA36S). Animals submitted to
      immobilization alone or to electroacupuncture (100 Hz, 2-4 V, faradic wave) in a
      non-point region were compared to animals submitted to electroacupuncture at
      EA36S (4 animals/subgroup). c-Fos expression was measured in 41 brain areas by
      simple counting of cells and the results are reported as number of c-Fos
      immunoreactive cells/10,000  m . The protocols of repeated immobilization
      significantly reduced the immobilization-induced c-Fos expression in most of the
      brain areas analyzed (P < 0.05). Animals of the EA36S groups had significantly
      higher levels of c-Fos expression in the dorsal raphe nucleus, locus coeruleus,
      posterior hypothalamus and central medial nucleus of the thalamus. Furthermore,
      the repeated immobilization protocols intensified the differences between the
      effects of 36S and non-point stimulation in the dorsal raphe nucleus (P < 0.05).
      These data suggest that high levels of stress can interact with and mask the
      evaluation of specific effects of acupuncture in unanesthetized animals.

PMID- 14666253
TI  - Absence-like seizures in adult rats following pilocarpine-induced status
      epilepticus early in life.
AB  - Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE)
      is induced at an early age. To determine in detail the electrophysiological
      patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17
      days old, were subjected to SE induced by pilocarpine and electro-oscillograms
      from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as
      head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120
      days later. Six control animals of the same age range did not show any signs of
      epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1  
      0.5 Hz in frequency, 18.9   9.1 s in duration) were recorded from the frontal
      cortex during absence fits. However, similar spike-wave discharges were always
      found also in the hippocampus and, less frequently, in the amygdala and in
      thalamic nuclei. Repetitive or single spikes were also detected in these same
      central structures. Clonic movements and single jerks were recorded from all the
      rats, either concomitantly with or independently of the spike-wave complexes and
      spikes. We conclude that rats made epileptic with pilocarpine develop absence
      seizures also occurring during paradoxical sleep, showing the characteristic
      spike-wave bursts in neocortical areas and also in the hippocampus. This is in
      contrast to the well-accepted statement that one of the main characteristics of
      absence-like fits in the rat is that spike-wave discharges are never recorded
      from the hippocampal fields.

PMID- 14666254
TI  - Evidence that urocortin is absent from neurons of the Edinger-Westphal nucleus in
      pigeons.
AB  - The Edinger-Westphal nucleus (EWN) is a central preganglionic parasympathetic
      cell group that gives rise to cholinergic input to the ciliary ganglion, thereby
      regulating several neurovegetative ocular functions. Recently, the supposed
      presence of the neuropeptide urocortin (UCN) has been reported in EWN neurons in
      rodent brain. The purpose of the present study was to examine the distribution of
      UCN in avian brain and to investigate by immunohistochemical analysis the
      possible use of this substance as an EWN marker in a non-mammalian class of
      vertebrates. Brain tissue of pigeons was incubated with a specific antibody
      against UCN and the results showed labeling of many small neurons, forming a
      double wing in the dorsal mesodiencephalic transition area. Their size and shape,
      however, differed from those of EWN neurons, and they were preferentially located
      rostral to the EWN. Double-label experiments employing an antibody against the
      enzyme choline acetyltransferase (ChAT) showed that UCN is not localized to the
      cholinergic cells of the EWN and confirmed the rostral distributionof UCN never
      overlapping the ChAT+ EWN cells. Taken together, these results suggest that, at
      least in pigeons, the UCN+ population does not belong to the traditionally
      defined EWN.

PMID- 14666255
TI  - The L-arginine/nitric oxide/cyclic-GMP pathway apparently mediates the peripheral
      antihyperalgesic action of fentanyl in rats.
AB  - There are only a few studies on the molecular mechanisms underlying the
      peripheral antihyperalgesic effect of opioids. The aim of this study was to
      investigate the molecular bases of the peripheral antihyperalgesic effect of
      fentanyl in a model of prostaglandin-induced chemical hyperalgesia. Prostaglandin
      E2 (1.4 nmol) injected into one hind paw of male Wistar rats (200-250 g, N = 6 in
      each experimental or control group) pretreated with indomethacin (2.5 mg/kg)
      potentiated the nocifensive response to formalin (1%) injection made 60 min
      later. Drugs applied locally 30 min after prostaglandin E2 induced the following
      effects: fentanyl (0.1-1.0 nmol) caused a dose-dependent reversal of the
      hyperalgesic state, naloxone (2 nmol) co-injected with fentanyl (1 nmol)
      completely reversed the antihyperalgesic effect, Nomega-nitro-L-arginine (NOARG,
      0.05-0.2 mol) in combination with fentanyl (1.0 nmol) caused a dose-dependent
      inhibition of the antihyperalgesic effect of fentanyl, co-administration of L
      arginine (0.5 mol) with NOARG (0.2 mol) plus fentanyl (1.0 nmol) fully restored
      the antihyperalgesic effect, and the cyclic-GMP phosphodiesterase inhibitor UK
      114,542-27 (5-[2-ethoxy-5-(morpholinylacetyl) phenyl]-1,6-dihydro-1-methyl-3
      propyl-7H-pyrazolo [4,3-d]-pyrimidin-7-one methanesulfonate monohydrate; 0.5-2.0
      mol) potentiated a subeffective dose of fentanyl (0.1 nmol) in a dose-dependent
      manner. However, UK-114,542-27 (2.0 mol) injected alone did not produce this
      antihyperalgesic effect. Systemically administered fentanyl (1.0 nmol, sc) did
      not cause antinociception. Taken together, these results support the view that
      fentanyl reverses prostaglandin E2-induced hyperalgesia, probably by activating
      an opioid receptor at the periphery, and furthermore the L-arginine/nitric
      oxide/cyclic-GMP pathway may mediate this peripheral effect of fentanyl.

PMID- 14666256
TI  - Effect of electrolytic lesion of the dorsal raphe nucleus on water intake and
      sodium appetite.
AB  - The present study determined the effect of an electrolytic lesion of the dorsal
      raphe nucleus (DRN) on water intake and sodium appetite. Male Wistar rats
      weighing 290-320 g with a lesion of the DRN (L-DRN), performed two days before
      experiments and confirmed by histology at the end of the experiments, presented
      increased sensitivity to the dehydration induced by fluid deprivation. The
      cumulative water intake of L-DRN rats reached 23.3   1.9 ml (a 79% increase, N =
      9) while sham-lesioned rats (SL-DRN) did not exceed 13.0   1.0 ml (N = 11, P <
      0.0001) after 5 h. The L-DRN rats treated with isoproterenol (300  g kg-1 ml-1,
      sc) exhibited an increase in water intake that persisted throughout the
      experimental period (L-DRN, 15.7   1.47 ml, N = 9 vs SL-DRN, 9.3   1.8 ml, N =
      11, P < 0.05). The L-DRN rats also showed an increased spontaneous sodium
      appetite during the entire period of assessment. The intake of 0.3 M NaCl after
      12, 24, 36 and 72 h by the L-DRN rats was always higher than 20.2   4.45 ml (N =
      10), while the intake by SL-DRN was always lower than 2.45   0.86 ml (N = 10, P <
      0.00001). Sodium- and water-depleted L-DRN rats also exhibited an increased
      sodium appetite (13.9   2.0 ml, N = 11) compared to SL-DRN (4.6   0.64 ml, N =
      11) after 120 min of observation (P < 0.02). The sodium preference of L-DRN rats
      in both conditions was always higher than that of SL-DRN rats. These results
      suggest that electrolytic lesion of the DRN overcomes a tonic inhibitory
      component of sodium appetite.

PMID- 14666257
TI  - Inhibition of the sarcoplasmic reticulum Ca2+ pump with thapsigargin to estimate
      the contribution of Na+-Ca2+ exchange to ventricular myocyte relaxation.
AB  - Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the
      cytosol, which is performed by three main transport systems: sarcoplasmic
      reticulum Ca2+-ATPase (SR-A), Na+-Ca2+ exchanger (NCX) and the so-called slow
      mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake). To estimate
      the relative contribution of each system to twitch relaxation, SR Ca2+
      accumulation must be selectively inhibited, usually by the application of high
      caffeine concentrations. However, caffeine has been reported to often cause
      changes in membrane potential due to NCX-generated inward current, which
      compromises the reliability of its use. In the present study, we estimated
      integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch
      relaxation, and compared the results when using caffeine application (Cf-NT) and
      an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW).
      Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with
      indo-1. For transients in which one or more transporters were inhibited, Ca2+
      fluxes were estimated from the measured free Ca2+ concentration and myocardial
      Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was
      significantly higher with TG-TW than with Cf-NT (12 vs 7  M), whereas SR
      dependent flux was lower with TG-TW (77 vs 81  M). The relative participations of
      NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively) and SR-A (85 vs 89.5% with TG
      TW and Cf-NT, respectively) in total relaxation-associated Ca2+ flux were also
      significantly different. We thus propose TG-TW as a reliable alternative to
      estimate NCX contribution to twitch relaxation in this kind of analysis.

PMID- 14666258
TI  - Effect of the establishment of dominance relationships on cortisol and other
      metabolic parameters in Nile tilapia (Oreochromis niloticus).
AB  - The objective of the present study was to investigate the influence of the
      establishment of dominance relationships and social stress on plasma cortisol and
      metabolite levels in Nile tilapia (Oreochromis niloticus). During the 30-day
      experiment, the fish weighing 236   29 g were kept in individual aquaria, except
      for two pairings lasting 6 h each. Blood samples were taken from the animals
      before and after pairing. Display, approach, attack, rebuff, chase flight, and
      coloration were carried out on days 16 and 30. Activities and behaviors
      characteristic of the establishment of dominance relationships were described. It
      was possible to classify all experimental fish (N = 30) as dominant or
      subordinate. No differences were detected between dominant (N = 15) and
      subordinate (N = 15) fish during isolation or after pairing in cortisol
      (isolated: 5.76   0.98 vs 5.42   0.63; paired: 10.94   1.62 vs 11.21   2.45 
      g/dl), glucose (isolated: 60.02   4.9 vs 67.85   16.16; paired: 110.44   15.72 vs
      136.26   22.46 mg/dl), triglyceride (isolated: 167.87   5.06 vs 185.68   7.24;
      paired: 210.85   13.40 vs 221.82   12.70 mg/dl) or total protein levels
      (isolated: 7.01   0.42 vs 6.69   0.59; paired: 9.21   0.62 vs 9.51   0.66 g/dl).
      However, when isolated (N = 30) and paired (N = 30) tilapia were compared, there
      were significant differences in cortisol and metabolite levels. The similar
      response presented by dominant and subordinate tilapia indicates that
      establishment of dominance relationships was a stressor for both groups.

PMID- 14666259
TI  - Comparison of the efficacy of biodegradable and non-biodegradable scintillation
      liquids on the counting of tritium- and [14C]-labeled compounds.
AB  - The widespread use of H and 14C in research has generated a large volume of waste
      mixed with scintillation liquid, requiring an effective control and appropriate
      storage of liquid radioactive waste. In the present study, we compared the
      efficacy of three commercially available scintillation liquids, Optiphase HiSafe
      3, Ultima-Gold AB (biodegradable) and Insta-Gel-XF (non-biodegradable), in terms
      of [14C]-glucose and [ H]-thymidine counting efficiency. We also analyzed the
      effect of the relative amount of water (1.6 to 50%), radioisotope concentration
      (0.1 to 100 nCi/ml), pH (2 to 10) and color of the solutions (samples containing
      0.1 to 1.0 mg/ml of Trypan blue) on the counting efficiency in the presence of
      these scintillation liquids. There were few significant differences in the
      efficiency of 14C and H counting obtained with biodegradable or non-biodegradable
      scintillation liquids. However, there was an 83 and 94% reduction in the
      efficiency of 14C and H counting, respectively, in samples colored with 1 mg/ml
      Trypan blue, but not with 0.1 mg/ml, independent of the scintillation liquid
      used. Considering the low cost of biodegradable scintillation cocktails and their
      efficacy, these results show that traditional hazardous scintillation fluids may
      be replaced with the new safe biodegradable fluids without impairment of H and
      14C counting efficiency. The use of biodegradable scintillation cocktails
      minimizes both human and environmental exposure to hazardous solvents. In
      addition, some biodegradable scintillation liquids can be 40% less expensive than
      the traditional hazardous cocktails.

PMID- 14666260
TI  - Transitory increased blood pressure after upper airway surgery for snoring and
      sleep apnea correlates with the apnea-hypopnea respiratory disturbance index.
AB  - A transitory increase in blood pressure (BP) is observed following upper airway
      surgery for obstructive sleep apnea syndrome but the mechanisms implicated are
      not yet well understood. The objective of the present study was to evaluate
      changes in BP and heart rate (HR) and putative factors after
      uvulopalatopharyngoplasty and septoplasty in normotensive snorers. Patients (N =
      10) were instrumented for 24-h ambulatory BP monitoring, nocturnal respiratory
      monitoring and urinary catecholamine level evaluation one day before surgery and
      on the day of surgery. The influence of postsurgery pain was prevented by
      analgesic therapy as confirmed using a visual analog scale of pain. Compared with
      preoperative values, there was a significant (P < 0.05) increase in nighttime but
      not daytime systolic BP (119   5 vs 107   3 mmHg), diastolic BP (72   4 vs 67   2
      mmHg), HR (67   4 vs 57   2 bpm), respiratory disturbance index (RDI)
      characterized by apnea-hypopnea (30   10 vs 13   4 events/h of sleep) and
      norepinephrine levels (22.0   4.7 vs 11.0   1.3  g l-1 12 h-1) after surgery. A
      positive correlation was found between individual variations of BP and individual
      variations of RDI (r = 0.81, P < 0.01) but not between BP or RDI and
      catecholamines. The visual analog scale of pain showed similar stress levels on
      the day before and after surgery (6.0   0.8 vs 5.0   0.9 cm, respectively). These
      data strongly suggest that the cardiovascular changes observed in patients who
      underwent uvulopalatopharyngoplasty and septoplasty were due to the increased
      postoperative RDI.

PMID- 14666261
TI  - Duration-controlled swimming exercise training induces cardiac hypertrophy in
      mice.
AB  - Exercise training associated with robust conditioning can be useful for the study
      of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A
      swimming apparatus is described to control training regimens in terms of
      duration, load, and frequency of exercise. Mice were submitted to 60- vs 90-min
      session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no
      workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood
      pressure was unchanged in all groups while resting heart rate decreased in the
      trained groups (8-18%). Skeletal muscle citrate synthase activity, measured
      spectrophotometrically, increased (45-58%) only as a result of duration and
      frequency-controlled exercise training, indicating that endurance conditioning
      was obtained. In groups which received duration and endurance conditioning,
      cardiac weight (14-25%) and myocyte dimension (13-20%) increased. The best
      conditioning protocol to promote physiological hypertrophy, our primary goal in
      the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no
      overload attached to the body. Thus, duration- and frequency-controlled exercise
      training in mice induces a significant conditioning response qualitatively
      similar to that observed in humans.

PMID- 14666262
TI  - Normal HC11 and ras-transformed mouse mammary cells are resistant to the
      antiproliferative effects of retinoic acid.
AB  - The objective of the present study was to determine the effects of retinoic acid
      on the growth of the mouse mammary cells HC11 and HC11ras, which are a model for
      in vitro breast cancer progression. The expression of the two classes (RARs and
      RXRs) of retinoic acid receptor mRNAs was determined by Northern blot analysis.
      Receptor functional integrity was determined by testing whether RAR   mRNA could
      be induced by retinoic acid. The effects of a 72-h exposure to 50  M 13-cis
      retinoic acid on HC11 and HC11ras cell proliferation and HC11 cell
      differentiation were investigated by flow cytometric cell cycle analysis, and by
      determination of  -casein mRNA expression, respectively. The possibility that
      retinoic acid would induce the expression of the vitamin D receptor and synergize
      with vitamin D, a known inhibitor of HC11 cell growth, was also investigated.
      HC11 cells expressed higher mRNA levels of both RAR a and RAR g when compared to
      HC11ras cells. In contrast, RAR  , as well as RXR a,   and g expression was low
      in both HC11 and HC11ras cells. In addition, RAR   mRNA was induced by retinoic
      acid treatment in both cells. In spite of these observations, no effects were
      seen on cell proliferation or differentiation upon exposure to retinoic acid.
      Neither vitamin D receptor induction nor synergy with vitamin D on growth
      inhibition was observed. We conclude that the RAR expression profile could be
      related to the transformed state in HC11ras cells and that the retinoic acid
      resistance observed merits further investigation.

PMID- 14666263
TI  - Erythrocytes may contain a ouabain-insensitive K+-ATPase which plays a role in
      internal K+ balance.
AB  - Erythrocytes are useful in evaluating K+ transport pathways involved in internal
      K+ balance. Several forms of H+,K+-ATPase have been described in nephron segments
      active in K+ transport. Furthermore, the activity of a ouabain-insensitive
      isoform of H+,K+-ATPase expressed in collecting duct cells may be modulated by
      acid-base status. Various assays were performed to determine if a ouabain
      insensitive K+-ATPase is present in rat erythrocytes and, if so, whether it plays
      a role in internal K+ balance. Kinetic studies demonstrated that maximal
      stimulation of enzyme activity was achieved with 2.5 mM K+ at pH 7.4. Subsequent
      experiments were performed on erythrocyte membranes collected from animals
      submitted to varying degrees of K+ homeostasis: control rats, K+-depleted rats,
      K+-loaded rats, and rats rendered hyperkalemic due to acute renal failure. As
      observed in the collecting duct cell studies, there was a significant decrease in
      the activity of ouabain-insensitive K+-ATPase in the erythrocytes of both K+
      loaded and metabolically alkalotic K+-depleted rats. However, this enzyme
      activity in erythrocyte membranes of rats with metabolic acidosis-related
      hyperkalemia was similar to that of control animals. This finding may be
      interpreted as resulting from two potentially modulating factors: the stimulating
      effect that metabolic acidosis has on K+-ATPase and the counteracting effect that
      hyperkalemia and uremia have on metabolic acidosis. In summary, we present
      evidence of a ouabain-insensitive K+-ATPase in erythrocytes, whose activity is
      modulated by acid-base status and K+ levels.

PMID- 14666265
TI  - Initial experience in Brazil with the Helex septal occluder for percutaneous
      occlusion of atrial septal defects.
AB  - OBJECTIVE: To evaluate the initial clinical experience with the Helex septal
      occluder for percutaneous closure of atrial septal defects. METHODS: Ten patients
      underwent the procedure, 7 patients with ostium secundum atrial septal defects
      (ASD) with hemodynamic repercussions and 3 patients with pervious foramen ovale
      (PFO) and a history of stroke. Mean age was 33.8 years and mean weight was 55.4
      kg. Mean diameter by transesophageal echocardiography and mean stretched ASD
      diameter were 11.33   3.3mm, and 15.2   3.8mm, respectively. The Qp/Qs ratio was
      1.9   0.3 in patients with ASD. RESULTS: Eleven occluders were placed because a
      patient with 2 holes needed 2 devices. It was necessary to retrieve and replace 4
      devices in 3 patients. We observed immediate residual shunt (< 2mm) in 4 patients
      with ASD, and in those with patent foramen ovale total occlusion of the defect
      occurred. No complications were noted, and all patients were discharged on the
      following day. After 1 month, 2 patients with ASD experienced trivial residual
      shunts (1mm). In 1 patient, we observed mild prolapse in the proximal disk in the
      right atrium, without consequences. CONCLUSION: The Helex septal occluder was
      safe and effective for occluding small to moderate atrial septal defects. Because
      the implantation technique is demanding, it requires specific training of the
      operator. Even so, small technical failures may occur in the beginning of the
      learning curve, but they do not involve patient safety.

PMID- 14666266
TI  - Right ventricular structure and function as possible determinants of surgical
      outcome 30 years after repair of tetralogy of Fallot.
AB  - OBJECTIVE: To identify the variables that may be involved in the persistence of
      symptoms (functional class II, III, or IV vs. I) in patients being followed up
      for 30 years after surgical repair of tetralogy of Fallot. METHODS: Fifty-three
      patients (27 women), who underwent corrective surgery for tetralogy of Fallot
      between 1960 and 1970, were studied. Their ages ranged from 7 months to 26 years.
      At the end of follow-up, 13 patients were asymptomatic and the remaining were in
      functional class II (N=24), III (N=15), and IV (N=1). To differentiate
      asymptomatic from symptomatic patients, the following variables were analyzed:
      age at surgery, need for widening the pulmonary ring and trunk, need for a second
      (2nd OP) or 3rd operation, residual defect of the interventricular septum,
      residual regurgitation of the pulmonary valve, systolic gradient through the
      right ventricular outflow tract, right ventricular dilation or hypertrophy (RVH),
      cardiothoracic index (CTI), right and left ventricular ejection fraction
      (RVEF/LVEF), and arrhythmias. RESULTS: The univariate analysis showed an
      association between the presence of symptoms and the 2nd OP (P=0.03), an increase
      in the CTI (P=0.0001), moderate to severe RVH (P=0.002), and dilation (P=0.0003).
      In the logistic regression model, the combination of the 2nd OP (P=0.008), the
      RVH (P=0.002), and the reduction in RVEF (P=0.01) determined the presence of
      symptoms. CONCLUSION: Despite the surgical treatment, right ventricular
      remodeling and performance were the major determinants in the late follow-up of
      tetralogy of Fallot.

PMID- 14666267
TI  - Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed
      with fluorescence in situ hybridization.
AB  - OBJECTIVE: To evaluate the cardiovascular findings and clinical follow-up of
      patients with Williams-Beuren syndrome. METHODS: We studied 20 patients (11
      males, mean age at diagnosis: 5.9 years old), assessed for cardiovascular
      abnormalities with electrocardiography and Doppler echocardiography. Fluorescence
      in situ hybridization (FISH) was used to confirm the diagnosis of the syndrome.
      RESULTS: Elastin gene locus microdeletion was detected in 17 patients (85%)
      (positive FISH), and in 3 patients deletion was not detected (negative FISH).
      Sixteen patients with a positive FISH (94%) had congenital cardiovascular disease
      (mean age at diagnosis: 2,3 years old). We observed isolated (2/16) supravalvular
      aortic stenosis and supravalvular aortic stenosis associated (11/16) with
      pulmonary artery stenosis (4/11); mitral valve prolapse (3/11); bicuspid aortic
      valve (3/11); aortic coarctation (2/11), thickened pulmonary valve (2/11);
      pulmonary valvular stenosis (1/11); supravalvular pulmonary stenosis (1/11);
      valvular aortic stenosis (1/11); fixed subaortic stenosis (1/11); pulmonary
      artery stenosis (2/16) associated with pulmonary valvar stenosis (1/2) and with
      mitral valve prolapse (1/2); and isolated mitral valve prolapse (1/16). Four
      patients with severe supravalvular aortic stenosis underwent surgery (mean age:
      5.7 years old), and 2 patients had normal pressure gradients (mean follow-up: 8.4
      years). CONCLUSION: A detailed cardiac evaluation must be performed in all
      patients with Williams-Beuren syndrome due to the high frequency of
      cardiovascular abnormalities.

PMID- 14666268
TI  - Clinical significance of transient left ventricular dilation assessed during
      myocardial Tc-99m sestamibi scintigraphy.
AB  - OBJECTIVE: To assess the clinical significance of transient ischemic dilation of
      the left ventricle during myocardial perfusion scintigraphy with stress/rest
      sestamibi. METHODS: The study retrospectively analyzed 378 patients who underwent
      myocardial perfusion scintigraphy with stress/rest sestamibi, 340 of whom had a
      low probability of having ischemia and 38 had significant transient defects.
      Transient ischemic dilation was automatically calculated using Autoquant
      software. Sensitivity, specificity, and the positive and negative predictive
      values were established for each value of transient ischemic dilation. RESULTS:
      The values of transient ischemic dilation for the groups of low probability and
      significant transient defects were, respectively, 1.01   0.13 and 1.18   0.17.
      The values of transient ischemic dilation for the group with significant
      transient defects were significantly greater than those obtained for the group
      with a low probability (P<0.001). The greatest positive predictive values, around
      50%, were obtained for the values of transient ischemic dilation above 1.25.
      CONCLUSION: The results suggest that transient ischemic dilation assessed using
      the stress/rest sestamibi protocol may be useful to separate patients with
      extensive myocardial ischemia from those without ischemia.

PMID- 14666269
TI  - Noninvasive cardiac assessment in children of women with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Noninvasive cardiac assessment of newborns and infants of women with
      systemic lupus erythematosus. The children had no congenital total
      atrioventricular block and were compared with the children of healthy women.
      METHODS: We prospectively assessed 13 newborns and infants aged 1 to 60 days,
      children of women with systemic lupus erythematosus and without congenital total
      atrioventricular block. These children were compared with 30 children of women
      who had no lupus or anti-Ro/SSA antibodies, and no risk factors for congenital
      heart disease either. Their age groups matched. The following examinations were
      performed: cardiological physical examination, electrocardiography,
      echocardiography, and signal-averaged electrocardiography. RESULTS: The
      statistical analysis showed no significant difference in ventricular function or
      in the cardiac conduction system between the groups. CONCLUSION: In regard to the
      conduction system and ventricular function in the absence of total
      atrioventricular block, no statistically significant difference was observed
      between the children of women with systemic lupus erythematosus and children of
      healthy women.

PMID- 14666270
TI  - Comparison of immediate results and follow-up of patients with single-vessel and
      multivessel coronary artery disease younger than 50 years of age undergoing
      coronary stent implantation.
AB  - OBJECTIVE: To assess the in-hospital results and clinical follow-up of young
      patients (< 50 years) with multivessel coronary artery disease undergoing stent
      implantation in native coronary arteries and to compare their results with those
      of patients with single-vessel coronary artery disease. METHODS: We
      retrospectively studied 462 patients undergoing coronary stent implantation.
      Patients were divided into 2 groups: group I (G-I) - 388 (84%) patients with
      single-vessel coronary artery disease; and group II (G-II) - 74 (16%) patients
      with multivessel coronary artery disease. RESULTS: The mean age of the patients
      was 45 4.9 years, and the clinical findings at presentation and demographic data
      were similar in both groups. The rate of clinical success was 95% in G-I and
      95.8% in G-II (P=0.96), with no difference in regard to in-hospital evolution
      between the groups. Death, acute myocardial infarction, and the need for
      myocardial revascularization during clinical follow-up occurred in 10.1% and
      11.2% (P=0.92) in G-I and G-II, respectively. By the end of 24 months, the
      actuarial analysis showed an event-free survival of 84.6 % in G-I and 81.1% in G
      II (P=0.57). CONCLUSION: Percutaneous treatment with coronary stent implantation
      in young patients with multivessel disease may be safe with a high rate of
      clinical success, a low incidence of in-hospital complications, and a favorable
      evolution in clinical follow-up.

PMID- 14666271
TI  - Female alcoholics: electrocardiographic changes and associated metabolic and
      electrolytic disorders.
AB  - OBJECTIVE: To identify the electrocardiographic changes and their associations
      with metabolic and electrolytic changes in female alcoholics. METHODS: The study
      comprised 44 female alcoholics with no apparent physical disorder. They underwent
      the following examinations: conventional electrocardiography; serologic tests for
      syphilis, Chagas' disease, and hepatitis B and C viruses; urinary pregnancy
      testing; hematimetric analysis; biochemical measurements of albumin, fibrinogen,
      fasting and postprandial glycemias, lipids, hepatic enzymes, and markers for
      tissue necrosis and inflammation. RESULTS: Some type of electrocardiographic
      change was identified in 33 (75%) patients. In 17 (38.6%) patients, more than one
      of the following changes were present: prolonged QTc interval in 24 (54.5%),
      change in ventricular repolarization in 11(25%), left ventricular hypertrophy in
      6 (13.6%), sinus bradycardia in 4 (9.1%), sinus tachycardia in 3 (6.8%), and
      conduction disorder in 3 (6.8%). The patients had elevated mean serum levels of
      creatine phosphokinase, aspartate aminotransferases, and gamma glutamyl
      transferase, as well as hypocalcemia and low levels of total cholesterol and LDL
      cholesterol. The patients with altered electrocardiograms had a more elevated
      age, a lower alcohol consumption, hypopotassemia, and significantly elevated
      levels of triglycerides, postprandial glucose, sodium and gamma glutamyl
      transferase than those with normal electrocardiograms. The opposite occurred with
      fasting glycemia, magnesium, and alanine aminotransferase. CONCLUSION: The
      electrocardiographic changes found were prolonged QTc interval, change in
      ventricular repolarization, and left ventricular hypertrophy. Patients with
      normal and abnormal electrocardiograms had different metabolic and electrolytic
      changes.

PMID- 14666272
TI  - A change in the treatment of abdominal aortic aneurysms.
AB  - OBJECTIVE: One of the most exciting potential applications of percutaneous
      therapy is the treatment of abdominal aneurysms. METHODS: Of 230 patients treated
      with a self-expanding polyester-lined stent-graft for different aortic
      pathologies at our institution, we selected 80 abdominal aneurysm cases
      undergoing treatment (from May 1997 to December 2002). The stent was introduced
      through the femoral artery, in the hemodynamic laboratory, with the patient under
      general anesthesia, with systemic heparinization, and induced hypotension.
      RESULTS: The procedure was successful in 70 (92.9%) cases; 10 patients with
      exclusion of abdominal aortic aneurysms were documented immediately within the
      hemodynamic room and 5 patients persisted with a residual leak. Two surgical
      conversions were necessary. Additional stent-grafts had to be inserted in 3
      (3.7%) cases. In the follow-up, 91.4% of patients were alive at a mean follow-up
      of 15.8 months. CONCLUSION: We believe that stent-grafts are an important tool in
      improving the treatment of abdominal aneurysms, and this new policy may change
      the conventional medical management of these patients.

PMID- 14666273
TI  - [Spondylodiscitis as a clinical manifestation of infective endocarditis].

PMID- 14666274
TI  - [Clinic-radiographic correlation: case 11/2003 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP ].

PMID- 14666275
TI  - [B-type natriuretic peptide and cardiovascular disease].

PMID- 14666276
TI  - Medical care and deaths due to coronary artery disease in Brazil, 1980-1999.
AB  - OBJECTIVE: To estimate the frequency of medical care preceding deaths due to
      coronary artery diseases (CAD) in different Brazilian regions and capitals and to
      describe trends in medical care from 1980 to 1999. METHODS: Information on
      medical care preceding deaths due to coronary artery diseases/acute myocardial
      infarction in adults > 20 years from 1980 to 1999 was collected in the DATASUS,
      the databank of the Brazilian Health Ministry. Sex, states, and capitals selected
      for 1999 were analyzed in the study. Medical care was stratified as follows:
      with, without, and ignored medical care. The descriptive analysis comprised
      frequencies, ratios of frequency, test for proportions, and increments or
      reductions in frequencies. RESULTS: Acute myocardial infarction (AMI) represented
      75 to 85% of the CAD in the period; the frequency of deaths with medical care
      ranged from 48.9 to 63%, and that of ignored medical care ranged from 27.2 to
      41.5%. The frequency of other CAD with medical care ranged from 56 to 76%. The
      frequency of deaths preceded by medical care decreased by 17.8%, and that with
      ignored medical care increased by 36.5% (RF=2). The values for the other CAD were
      -20.2% and +64.6% (RF=44.4). Deaths preceded by medical care were more frequent
      in females at all ages and in all Brazilian regions. CONCLUSION: The results show
      a high frequency of sudden death and suggest errors in diagnosis or codification
      and overestimation of the statistics about mortality. Validation of the death
      certificate diagnosis and frequent surveillance are required.

PMID- 14666277
TI  - The influence of patient's consciousness regarding high blood pressure and
      patient's attitude in face of disease controlling medicine intake.
AB  - OBJECTIVE: To assess the relation between blood pressure control and the
      following: the Morisky-Green test, the patient's consciousness regarding high
      blood pressure, the patient's attitude in face of medicine intake, the patient's
      attendance at medical consultations, and the subjective physician's judgment.
      METHODS: We studied 130 hypertensive patients with the following characteristics:
      73% females, 60 +/- 11 years, 58% married, 70% white, 45% retired, 45% with
      incomplete elementary schooling, 64% had a familial income of 1 to 3 minimum
      wages, body mass index of 30 +/- 7 kg/m , consciousness regarding the disease for
      a mean period of 11 +/- 9.5 years, and mean treatment duration of 8 +/- 7 years.
      RESULTS: Only 35% of the hypertensive individuals had blood pressure under
      control and a longer duration of treatment (10 +/- 7 vs 7 +/- 6.5 years; P<0.05).
      The retiree predominated. The result of the Morisky-Green test did not relate to
      blood pressure control. In evaluating the attitude in face of medicine intake,
      the controlled patients achieved significantly higher scores than did the
      noncontrolled patients (8 +/- 1.9 vs 7 +/- 2, P<0.05). The hypertensive patients
      had higher levels of consciousness regarding their disease and its treatment, and
      most (70%) patients attended 3 or 4 medical consultations, which did not
      influence blood pressure control. The physicians attributed significantly higher
      scores regarding adherence to treatment to controlled patients (6 +/- 0.8 vs 5 +/
      1.2; P<0.05). CONCLUSION: Consciousness regarding the disease, the Morisky-Green
      test, and attendance to medical consultations did not influence blood pressure
      control.

PMID- 14666278
TI  - Morphometric and topographic study of coronary ostia.
AB  - OBJECTIVE: To investigate the morphometric and topographic aspects of coronary
      ostia, correlating them with the aortic leaflets. METHODS: Fifty-one hearts with
      the great vessels attached were analyzed in this study. The ascending aorta was
      transversally sectioned 1 cm above the commissures of the aortic leaflets. The
      right and left coronary ostia were analyzed, as were the distances from these
      ostia to the bottom of the aortic sinuses and to the commissures of the aortic
      leaflets. RESULTS: The left coronary ostium was located below the
      intercommissural line in 42% of cases, above that line in 40% of cases, and at
      the level of that line in 18% of cases. The mean distance from the left coronary
      ostium to the bottom of the corresponding sinus was 12.6 +/- 2.61 mm. The right
      coronary ostium was located below the intercommissural line in 60% of cases,
      above that line in 28% of cases, and at the level of that line in 12% of cases.
      The mean distance from the right coronary ostium to the bottom of the
      corresponding aortic sinus was 13.2 +/- 2.64 mm. The mean diameters of the left
      and right coronary ostia were 4.75 +/- 0.93 mm and 3.46 +/- 0.94 mm,
      respectively. The mean diameters of the juxtamural portion of the left and right
      coronary arteries were 3.75 +/- 0.79 mm and 2.9 +/- 0.73 mm, respectively. In one
      case, both ostia were located in the left coronary sinus. CONCLUSION: The left
      coronary ostium may be located either above or below the intercommissural line.
      The right coronary ostium is predominantly located below the intercommissural
      line. The coronary ostia have reduced diameters as compared with the juxtamural
      diameters of their respective coronary arteries.

PMID- 14666279
TI  - Secular trends in a population with ischemic heart disease admitted to the
      Instituto do Coracao in Sao Paulo.
AB  - OBJECTIVE: To assess the clinical and demographic characteristics of a population
      with ischemic heart disease admitted in the final decades of the 20th century.
      METHODS: This study retrospectively assessed patients hospitalized with ischemic
      heart disease divided into the following 2 groups: acute group - 11.181 patients
      with acute myocardial infarction admitted from 1/1/82 to 12/31/94; and chronic
      group - 4.166 patients undergoing coronary artery bypass graft surgery from
      1/1/84 to 12/31/94. RESULTS: In the acute group, an increase in the percentage of
      females (from 22.7% to 27.7%, P<0.001) and diabetic individuals (from 12.4% to
      17.5%, P<0.001) was observed, as was an increase in age (from 57.4 +/- 11.5 to
      59.9 +/- 12.1 years, P<0.05). In-hospital mortality was greater among females
      (27.8% and 15.7%, P=0.001), among diabetic individuals (24.2% and 17.8%,
      P=0.001), and among the elderly (60.9 +/- 15.2 and 57.7 +/- 11.8 years,
      P=0.0001). In the chronic group, an increase in the percentage of females (from
      17.5% to 27.2%, P=0.001) was observed, as was an increase in age (from 56.3 +/-
      8.6 to 60.5 +/- 9.6 years, P=0.0001). In-hospital mortality was greater among
      females (8.3% and 5.8%, P<0.05) and among the elderly (58.1 +/- 9.1 and 62.1 +/-
      7.9 years, P=0.0001). CONCLUSION: The characteristics of the population studied
      with ischemic heart disease point towards a worse prognosis, due to the greater
      percentages of females, older patients, and diabetic patients, groups known to
      have greater in-hospital mortality.

PMID- 14666280
TI  - Prevalence of systemic hypertension in students aged 7 to 14 years in the
      municipality of Barbacena, in the State of Minas Gerais, in 1999.
AB  - OBJECTIVE: To detect the prevalence of systemic hypertension in children and to
      establish the relation between blood pressure levels and sex, age, ethnicity,
      weight, and height. METHODS: The prevalence of systemic hypertension and its
      relation to sex, age, ethnicity, weight, and height were studied in 611 students
      aged 7 to 14 years out of 19.928 students classified according to age, ethnicity,
      and sex, who underwent anthropometric evaluation and blood pressure measurement.
      Hypertensive individuals were considered those whose blood pressure level was >
      the 95th percentile for age and sex, confirmed on 3 examinations. RESULTS: The
      prevalence of hypertension was 16.6% in the first evaluation, and 4.6% and 2.5%
      in the subsequent evaluations. The mean blood pressure levels increased with age.
      Weight was important, not only to determine blood pressure in healthy children,
      but also to determine systemic hypertension in children, which was not observed
      with height despite the different studies. The prevalence of systemic
      hypertension in the different ethnic groups and the mean blood pressure levels
      according to sex were similar. CONCLUSION: In addition to routine physical
      examinations, age, weight, and appropriate cuff size should be considered when
      assessing blood pressure in children to prevent hypertension, morbidity and
      mortality, and to avoid placing a financial burden on health care providers.

PMID- 14666281
TI  - Fibrinolytic therapy for thrombosis in cardiac valvular prosthesis short and long
      term results.
AB  - OBJECTIVE: To assess the short- and long-term results of the use of streptokinase
      (SK) for the treatment of thromboses in cardiac valvular prostheses. METHODS:
      Seventeen patients with cardiac prosthetic thrombosis diagnosed by clinical,
      echocardiographic, and radioscopic findings underwent fibrinolytic treatment with
      a streptokinase bolus of 250,000 U followed by 100.000 U/hour. Short- and long
      term results were assessed by radioscopy and echocardiography. RESULTS: Of the 17
      patients, 12 had mechanical double-disk prostheses (4 aortic, 6 mitral, 2
      tricuspid), 4 had single-disk prostheses (2 aortic, 1 mitral, and 1 tricuspid),
      and 1 had a tricuspid bioprosthesis. The success rate was 64.8%, the partial
      success rate was 17.6%, and the nonsuccess rate was 17.6%. All patients with a
      double-disk prosthesis responded, completely or partially, to the treatment. None
      of the patients with a single-disk prosthesis had complete resolution of the
      thrombosis. The time of streptokinase infusion ranged from 6 to 80 hours (mean of
      56 h). The mortality rate due to the use of streptokinase was 5.8% and was
      secondary to cerebral bleeding. During streptokinase infusion, 3 (17.6%) embolic
      episodes occurred as follows: 1 cerebral, 1 peripheral, and 1 coronary. The
      rethrombosis index was 33% in a mean follow-up of 42 months. CONCLUSION: The use
      of fibrinolytic agents was effective and relatively safe in patients with primary
      thrombosis of a double-disk prosthesis. A fatal hemorrhagic complication occurred
      in 1 (5.8%) patient, and embolic complications occurred in 3 (17.6%) patients. In
      a mean 42-month follow-up, 67% of the patients were free from rethrombosis.

PMID- 14666282
TI  - Intrauterine ductus arteriosus constriction: analysis of a historic cohort of 20
      cases.
AB  - OBJECTIVE: To describe the relative incidence, presentation, and evolvement of
      fetuses with early ductus constriction. METHODS: Twenty fetal echocardiograms
      indicating ductus constriction were reviewed in a population of 7000 pregnants.
      RESULTS: The cases were divided into group A (related to maternal use of
      cyclooxygenase inhibitors [n=7] and group B (idiopathics [n=13]). Mean
      gestational age was 32.5 +/- 3.1 (27-38) weeks and maternal age was 28.2 +/- 8.5
      (17-42) years. Mean systolic velocity in the ductus was 2.22 +/- 0.34 (1.66-2.81)
      m/s, diastolic velocity 0.79 +/- 0.28 (0.45-1.5) m/s, and pulsatility index 1.33
      +/- 0.36 (0.52-1.83). Two cases of ductal occlusion were noted. In 65% of the
      cases, an increase occurred in the right cavities; in 90% of the cases, tricuspid
      or pulmonary regurgitation, or both, occurred, with functional pulmonary atresia
      in 1 case. Diastolic velocity was greater in group A (1.13 +/- 0.33) than in
      group B (0.68 +/- 0.15) (P=0.008). The other data were similar in the 2 groups.
      The evolvement was not favorable in 4 patients from group B, including 1 death
      and 2 cases of persistent pulmonary hypertension. CONCLUSION: The high incidence
      of idiopathic constriction of the ductus arteriosus suggests that its diagnosis
      is underestimated and that many cases of persistence of fetal circulation in
      newborns may be related to constriction of the ductus arteriosus not diagnosed
      during intrauterine life. Group B had a lower severity but a risk of an
      unfavorable evolvement, suggesting a distinct alteration.

PMID- 14666283
TI  - Cerebral infarction in autopsies of chagasic patients with heart failure.
AB  - OBJECTIVE: To determine the frequency of encephalic infarction and its
      contribution to lethality in patients with Chagas' disease and heart failure.
      METHODS: Medical records and autopsy reports of patients with Chagas' disease
      complicated by heart failure, who died at the Professor Edgar Santos Hospital of
      the Federal University of Bahia in the past 45 years were retrospectively
      analyzed. Data comprised information regarding the clinical history on hospital
      admission, complementary and anatomicopathological examinations, including the
      presence of encephalic infarction, the impaired region, and the cause of death.
      RESULTS: Of the 5,447 autopsies performed, 524 were in patients with heart
      failure due to Chagas' disease. The mean age was 45.7 years, and 51 (63%)
      patients were of the male sex. The frequency of encephalic infarction was 17.5%,
      corresponding to 92 events in 92 individuals, 82 (15.8%) of which involved the
      brain, 8 (1.5%) involved the cerebellum, and 2 (0.4%) involved the hypophysis.
      CONCLUSION: Cerebral infarction has been a frequent finding in autopsies of
      chagasic patients with heart failure, and it has been an important cause of death
      in our region. The presence of cerebral infarction and its complications have
      been associated with death in 52% of the cases studied.

PMID- 14666284
TI  - Aspergillus infection in the ascending aorta of a patient with aortic and mitral
      valve prostheses.
AB  - We report the case of implantation of metallic mitral and aortic valve prostheses
      6 months earlier, with subsequent multiple embolic episodes. The
      anatomicopathological examination of the thrombus of the third embolic episode
      was compatible with Aspergillus sp, which was treated with amphotericin B,
      followed by oral itraconazole. On the fourth embolism, vegetations were
      visualized in the ascending aorta on echocardiography and resonance imaging, and
      the patient underwent replacement of the aortic segment by a Haemashield tube and
      exploration of the aortic prosthesis, which was preserved, because no signs of
      endocarditis were found. Four months later, the patient died due to cardiogenic
      shock secondary to acute myocardial infarction caused by probable coronary
      embolism and partial dysfunction of the aortic prosthesis.

PMID- 14666285
TI  - [Case 5/03 - A 68 year-old smoker woman with a history of 20 years of cough and
      of 2 months of dyspnea at rest(Faculdade de Medicina da Pontificia Universidade
      Catolica, Campinas, SP)].

PMID- 14666286
TI  - [Case 10/2003 - Instituto do Coracao do Hospital das Clinicas da FMUSP].

PMID- 14666287
TI  - [3 decades of AMBP--24-hour ambulatory monitoring of blood pressure. Paradigm
      changes in the diagnosis and treatment of arterial hypertension].

PMID- 14666288
TI  - Hypertension and headache: a coincidence without any real association.

PMID- 14666289
TI  - Uterine artery embolization for the treatment of symptomatic myomas in Brazilian
      women.
AB  - CONTEXT: Uterine myomas are benign tumors that mostly occur in women of
      reproductive age at a frequency ranging from 20 to 25%. The symptoms are
      increased menstrual flow, pain and compressive signs. New treatments have been
      proposed and uterine artery embolization is one of them. OBJECTIVE: To evaluate
      the effects of treatment by embolization of the uterine artery, in women with
      symptomatic myomas. Uterine and dominant myoma volumes and the major symptoms
      were evaluated before treatment and 12 weeks later. TYPE OF STUDY: Open clinical
      trial. SETTING: A tertiary-care women's hospital. PARTICIPANTS: The study was
      conducted on 32 women with symptomatic single or multiple myomas of the uterine
      body, seen at the outpatient unit from May 2000 to September 2001. MAIN
      MEASUREMENTS: The patients were submitted to gynecological examination and
      abdominal and endovaginal pelvic ultrasonography, and the examinations were
      repeated 12 weeks after the first procedure. Uterine artery embolization using
      PVA (polyvinyl alcohol) particles of 355-700   was performed by catheterization
      of the right femoral artery in 30 women and by bilateral catheterization in two.
      RESULTS: Before embolization, the mean uterine volume of the 32 women was 455 cm 
      and the mean volume of the dominant myoma was 150 cm . Twelve weeks after
      embolization, the mean uterine volume was 256 cm  and the mean volume of the
      dominant myoma was 91 cm , with p < 0.01 in both cases. Twelve weeks after the
      treatment, all the women answered a questionnaire, which showed that 71% had
      improvement in menstrual regularity, 90% decreased menstrual volume and 81%
      shortened menstrual duration. The most frequent immediate post-procedure
      symptoms, established as complications, were pain (100%) and fatigue (34%). One
      woman had myoma degeneration and was submitted to myomectomy. CONCLUSION: The
      significant reduction in uterine and dominant myoma volume confirms the validity
      of the treatment of symptomatic myomas by the technique of uterine artery
      embolization in Brazilian women. There was significant reduction in menstrual
      flow and duration, as well as better cycle regularity in the women studied. The
      few adverse effects observed in the sample studied mainly involved pain
      immediately after embolization.

PMID- 14666290
TI  - Role of video-assisted thoracoscopic sympathectomy in the treatment of primary
      hyperhidrosis.
AB  - CONTEXT: Essential hyperhidrosis is a frequent disorder causing significant
      functional impairment. The advent and development of video-assisted thoracoscopic
      techniques now allows thoracic sympathectomy to be carried out precisely and
      safety with good results and minimal morbidity. OBJECTIVE: To assess the impact
      of video-assisted thoracic sympathectomy in patients diagnosed as presenting
      severe and disabling hyperhidrosis. TYPE OF STUDY: This was a longitudinal study
      of the clinical course of all hyperhidrosis cases selected for surgery between
      May 1999 and January 2003. SETTING: Division of Thoracic Surgery, Universidade
      Federal de S o Paulo (UNIFESP). PARTICIPANTS: 743 patients with surgery indicated
      due to palmar hyperhidrosis (49.8%), palmar-axillary hyperhidrosis (38.1%),
      craniofacial hyperhidrosis (8.9%) or isolated axillary hyperhidrosis (2.8%).
      PROCEDURES: Video-thoracoscopic sympathectomy was performed, isolating the second
      thoracic ganglion (T2) in all patients, with additional sympathectomy of T3 and
      T4 if necessary. MAIN MEASUREMENTS: The clinical course was followed up via
      questionnaires, phone calls, letters and statements. Simple questions were asked
      regarding the disappearance of symptoms and presence and intensity of
      compensatory sweating. RESULTS: The surgery was regarded as efficient in all
      cases of palmar hyperhidrosis. In the craniofacial hyperhidrosis cases, partial
      recurrence of the symptoms occurred in 2 cases (3.0%). Partial recurrence or
      persistence of symptoms occurred in 20% of the patients with predominantly
      axillary symptomatology. The compensatory sweating was considered disagreeable or
      uncomfortable by about 30% of the patients, but it only reached the level of
      regretting the operation for 3% of them. This occurred more frequently in
      patients with axillary hyperhidrosis. Ten cases of complications occurred.
      CONCLUSION: Thoracoscopic sympathectomy provides very good results in most
      patients, with a very low complication rate. However, the assessment of surgical
      results using conventional methods is imprecise and inaccurate. Different
      methodology, including quality of life assessment, must be used for comparing
      results and providing objective data on the results of this operation.

PMID- 14666291
TI  - Pulmonary tuberculosis: tomographic evaluation in the active and post-treatment
      phases.
AB  - CONTEXT: Adequate knowledge of images consistent with tuberculosis activity is an
      important resource for tuberculosis diagnosis and treatment. OBJECTIVE: To
      evaluate the structural alterations caused by tuberculosis in the pulmonary
      parenchyma, both during the active phase of the disease and after the end of the
      treatment, through computerized tomography of the thorax. TYPE OF STUDY:
      Prospective study. SETTING: Pulmonary Division, Hospital das Clinicas, Faculdade
      de Medicina da Universidade de Sao Paulo. PARTICIPANTS: 20 patients, carriers of
      pulmonary tuberculosis, confirmed by Mycobacterium tuberculosis culture.
      PROCEDURES: Conventional tomography scans of the patients were obtained at two
      times: upon diagnosis and after the end of the treatment. The following were
      considered suggestive signs of tuberculosis activity: centrilobular nodules with
      segmented distribution, confluent micronodules, consolidations, thick-walled
      cavities, nodules, masses, thickening of the bronchial walls, tree-in-bud
      appearance and cylindrical bronchiectasis. MAIN MEASUREMENTS: The presence of
      suggestive signs of tuberculosis activity was compared between the start and the
      end of treatment by means of the signs test (z). RESULTS: All patients (20/20)
      presented suggestive signs of tuberculosis activity at the start of treatment.
      After the end of treatment, 13 patients (13/20) still presented some suggestive
      signs consistent with activity. A reduction in the extent of lung attack was seen
      post-treatment, in relation to its start (z = 10.10). This change was
      statistically significant (p < 0.001). CONCLUSION: Signs suggestive of
      tuberculosis activity are present in the active disease and are seen via computed
      tomography. The extent of parenchymal attack significantly decreases following
      treatment. Such signs may be useful in the diagnosis of pulmonary tuberculosis.

PMID- 14666292
TI  - Inactivation of the p15 gene in children with acute lymphoblastic leukemia.
AB  - CONTEXT: Tumor suppressor genes act on the control of cell cycle progression. In
      pediatric neoplasias, some of these genes may be considered to be markers for
      diagnosis or relapse, thus probably representing prognostic indicators.
      OBJECTIVE: To study the inactivation of the p15 gene in children with acute
      lymphoblastic leukemia. TYPE OF STUDY: Retrospective study. SETTING: Laboratory
      of Molecular Biology, Department of Pediatrics, Faculdade de Medicina de Ribeirao
      Preto, Universidade de Sao Paulo. PARTICIPANTS: Eighty-three children and
      adolescents with acute lymphoblastic leukemia were studied, with the examination
      of 83 bone marrow samples obtained at diagnosis, four obtained also during
      relapse, and two cerebrospinal fluid samples obtained from two cases of isolated
      relapse in the central nervous system. MAIN MEASUREMENTS: Homologous deletion of
      the p15 gene by multiplex polymerase chain reaction, and screening for point
      mutations by polymerase chain reaction/single-strand conformational polymorphism.
      RESULTS: Deletion of exon 2 of the p15 gene was observed in 15 children,
      including one case in which deletion was only verified during isolated central
      nervous system relapse. No case of exon 1 deletion, or that was suggestive of
      point mutations, was observed and no association between p15 gene inactivation
      and classic risk factors was established. CONCLUSION: According to the
      literature, inactivation of the p15 gene by deletion of exon 2 in acute
      lymphoblastic leukemia found in the population studied would be considered to be
      a molecular marker for diagnosis or relapse. However, no correlation between p15
      gene deletion and clinical prognostic indicators was observed.

PMID- 14666293
TI  - Dejerine-Sottas disease: a case report.
AB  - CONTEXT: Hereditary peripheral neuropathies (hereditary motor-sensory
      neuropathies or hereditary demyelinating neuropathies) are abnormalities of
      Schwann cells and their myelin sheaths, with peripheral nerve dysfunction. They
      include Charcot-Marie-Tooth disease, Dejerine-Sottas disease, congenital
      hypomyelinating neuropathy and hereditary neuropathy with liability to pressure
      palsy. OBJECTIVE: The objective of the present work was to describe a case of
      Dejerine-Sottas disease. CASE REPORT: A 9-year-old boy presented progressive
      slight motor deficit in the lower limbs, particularly in the feet, and
      generalized hyporeflexia. Electromyography disclosed significant reduction in
      motor and sensory nerve conduction velocities. Sural nerve biopsy showed axons
      surrounded by a thin myelin sheath and concentrically arranged cytoplasmic
      processes of Schwann cells forming onion-bulbs. No axon damage was observed.

PMID- 14666294
TI  - Meigs' syndrome with elevated CA 125: case report.
AB  - CONTEXT: Meigs' syndrome consists of a benign ovarian tumor accompanied by
      ascites and hydrothorax. Elevated serum CA 125 levels in postmenopausal women
      with solid adnexal masses, ascites and pleural effusion are highly suggestive for
      malignant ovarian tumor. However, patients with Meigs' syndrome can also have
      elevated serum CA 125 levels. The authors report a case of Meigs' syndrome with
      elevated CA 125 level. OBJECTIVE: This is a case report of Meigs' syndrome with
      elevated CA 125 level. CASE REPORT: A 65-year-old Brazilian woman had presented
      progressive dyspnea, weight loss and decline in general condition over the 7
      months preceding admission to our service. In another hospital, the patient had
      been submitted to thoracic drainage due to pleural effusion. With recurrence of
      the pleural effusion and increase in abdominal volume due to ascites and a pelvic
      mass, the patient sought our service. Transvaginal ultrasound showed an extensive
      adnexal solid mass of 16.4 x 10.8 cm located in the pelvis without exact limits,
      and the serum CA 125 level was elevated. With a preoperative diagnosis of ovarian
      carcinoma, the patient was submitted to exploratory laparotomy, which revealed a
      left ovarian tumor. The frozen section diagnosis was thecoma. Total abdominal
      hysterectomy with bilateral salpingo-oophorectomy was performed. The histology of
      the specimen confirmed the diagnosis of thecoma. The patient was asymptomatic
      with a normal serum CA 125 level 20 months after the operation.

PMID- 14666295
TI  - Sputum induction: review of literature and proposal for a protocol.
AB  - Since the 1980s, sputum induction by inhalation of hypertonic saline has been
      successfully used for diagnosing Pneumocystis carinii pneumonia in patients
      infected with HIV. In recent years, sputum induction and its subsequent
      processing has been refined as a noninvasive research tool providing important
      information about inflammatory events in the lower airways, and it has been used
      for studying various illnesses. In asthma, one application is to use sputum
      inflammatory indices to increase our understanding of complex relationships
      between inflammatory cells, mediators, and cytokine mechanisms. In chronic
      obstructive pulmonary disease, sputum assessment could be used as a screening
      test before deciding on long-term corticosteroid treatment. In tuberculosis,
      sputum induction is a valuable diagnostic tool for HIV-seropositive patients who
      do not produce sputum. Sputum induction appears to be a relatively safe,
      noninvasive means of obtaining airway secretions from subjects with cystic
      fibrosis, especially from those who do not normally produce sputum. Moreover,
      sputum induction can also be used in chronic cough and lung cancer. Generally,
      induction is performed through ultrasonic nebulizers, using hypertonic saline. It
      is recommended that sputum be processed as soon as possible, with complete
      homogenization by the use of dithiothreitol. We have also shown in this article
      an example of a protocol for inducing and processing sputum employing a nebulizer
      produced in Brazil.

PMID- 14666296
TI  - [Perinatal mortality associated factors in a general hospital of Chiapas,
      Mexico].
AB  - OBJECTIVE: To identify socioeconomic, gynecological-obstetric and fetal factors
      associated with perinatal mortality. METHODS: A matched case-control study was
      carried out. Cases were newborns (born live or dead) that were born and died
      between 28 weeks gestation and 7 days of life. Controls were live newborns
      between 28 weeks gestation and 7 days of life. A total of 99 cases and 197
      controls were studied. Data were obtained from the corresponding medical charts.
      Statistical analysis was performed using Stata 6.0 software. RESULTS: Mean
      maternal age was 24.82 years and mean newborn age was 37.78 weeks gestation with
      an average birth weight of 2,760 grams. Factors associated with perinatal
      mortality were: father's occupation as a farmer (adjusted odds ratio (OR)=3.31;
      95% CI=1.26-8.66); high obstetric risk index (adjusted OR=10.57; 95% CI=2.82
      39.66), cesarean birth (adjusted OR=2.75; 95% CI=1.37-5.51), five or more
      prenatal visits (adjusted OR=4.43; 95% CI=1.86-10.54) and preterm fetal maturity
      indices (PEG, APG, GEG) (adjusted OR=9.20; 95% CI=4.39-19.25). CONCLUSIONS: The
      risk factors associated with perinatal mortality found in the study are
      consistent with the findings reported in the international literature. These
      results show that prevention and control measures should be implemented to
      identify at risk pregnant women in order to lower perinatal mortality.

PMID- 14666297
TI  - Infant mortality and low birth weight in cities of Northeastern and Southeastern
      Brazil.
AB  - OBJECTIVE: To compare estimates of low birth weight (LBW), preterm birth, small
      for gestational age (SGA), and infant mortality in two birth cohorts in Brazil.
      METHODS: The two cohorts were performed during the 1990s, in S o Lu s, located in
      a less developed area in Northeastern Brazil, and Ribeir o Preto, situated in a
      more developed region in Southeastern Brazil. Data from one-third of all live
      births in Ribeir o Preto in 1994 were collected (2,839 single deliveries). In S o
      Lu s, systematic sampling of deliveries stratified by maternity hospital was
      performed from 1997 to 1998 (2,439 single deliveries). The chi-squared (for
      categories and trends) and Student t tests were used in the statistical analyses.
      RESULTS: The LBW rate was lower in S o Lu s, thus presenting an epidemiological
      paradox. The preterm birth rates were similar, although expected to be higher in
      Ribeir o Preto because of the direct relationship between preterm birth and LBW.
      Dissociation between LBW and infant mortality was observed, since S o Lu s showed
      a lower LBW rate and higher infant mortality, while the opposite occurred in
      Ribeir o Preto. CONCLUSIONS: Higher prevalence of maternal smoking and better
      access to and quality of perinatal care, thereby leading to earlier medical
      interventions (cesarean section and induced preterm births) that resulted in more
      low weight live births than stillbirths in Ribeir o Preto, may explain these
      paradoxes. The ecological dissociation observed between LBW and infant mortality
      indicates that the LBW rate should no longer be systematically considered as an
      indicator of social development.

PMID- 14666298
TI  - [Infant mortality in Brazil during recent periods of economic crisis].
AB  - OBJECTIVE: To analyze time trends in infant mortality in Brazil during a recent
      period of economic crisis (1980-1998). METHODS: Time-series study based on the
      Ministry of Health's Mortality Information System, IBGE Foundation and Funda  o
      Nacional de Sa de (National Health Institute database. Serial parameters were
      described using autoregressive integrated moving average (ARIMA) models, and the
      association between infant mortality rates and a number of determinants was
      evaluated using Spearman correlation coefficients. RESULTS: Infant mortality
      showed a declining trend (-59.3%) and a strong correlation with most of the
      indicators analyzed. However, only correlations between infant mortality rate and
      total pregnancy and birth rates presented a significant difference between the
      two decades. CONCLUSIONS: Variations in pregnancy rate were the main cause for
      the persistent decline in infant mortality in the 1980's. In the subsequent
      period, causes related to living conditions, especially healthcare, may have been
      more important.

PMID- 14666299
TI  - [Ischemic heart disease: mortality in natives and migrants, Sao Paulo, Brazil,
      1979-1998].
AB  - OBJECTIVE: The State of S o Paulo has been a major center of attraction for
      foreign and Brazilian migrants since the 19th century. The pattern of mortality
      due to ischemic heart disease according to place of birth is, however, unknown.
      Thus, the objective of the study was to identify differences in mortality due to
      ischemic heart disease among residents of the State of S o Paulo according to
      their place of birth. METHODS: Analytical time series study based on secondary
      data. Rates were not calculated due to lack of denominators. Instead, non-census
      indicators (proportional mortality and standardized mortality ratio weighted for
      years of potential life lost before the age of 100 years) and medians were
      utilized. Temporal trends were analyzed by means of simple linear regression.
      RESULTS: In the State of S o Paulo, about 40% of deaths due to ischemic heart
      disease occurred among migrants. The trend was negative for foreigners and
      positive for Brazilian migrants. Those born in northeastern Brazil, who presented
      the highest percentage of deaths in hospitals, had the worst performance: their
      proportional mortality due to ischemic heart disease remained unchanged
      throughout the study period (while this clearly declined for all other groups)
      and they died at younger ages. CONCLUSIONS: Migrants' share of total deaths due
      to ischemic heart disease in the State of S o Paulo is very high. While there is
      a declining trend for foreigners, it is growing among Brazilian migrants. Among
      the compared groups, mortality due to ischemic heart disease in the State of S o
      Paulo is most prominent for those born in northeastern Brazil.

PMID- 14666300
TI  - [Multiple-causes-of-death related to tuberculosis in the State of Sao Paulo,
      Brazil, 1998].
AB  - OBJECTIVES: The goal of this paper is to investigate mortality related to
      tuberculosis in the state of S o Paulo, southeastern Brazil, according to
      multiple causes of death and their interrelation with other underlying causes.
      METHODS: The study investigated deaths related to tuberculosis that occurred in
      the state of S o Paulo in 1998. Data were obtained from the Fundacao Sistema
      Estadual de Analise de Dados (State System for Data Analysis Foundation - SEADE)
      database. Causes of death by clinical forms of TB were coded in block A15-A19,
      and by its sequelae in category B90, according to the guidelines proposed by the
      Tenth Revision of the International Statistical Classification of Diseases and
      Related Health Problems. Tabulador de Causas Multiplas (Multiple Cause Tabulator 
      TCM) software was used for processing associated causes of death. Statistical
      analysis included analysis of variance, Student's t -distribution, and chi
      squared tests. RESULTS: TB was the underlying cause of 1,644 deaths, a
      4.6/100,000 population mortality rate. Main associated causes were respiratory
      failure (46,9%), pneumonias (16.5%), other specified symptoms and signs involving
      circulatory and respiratory systems (13.9%), cachexia (12.9%), diseases of the
      circulatory system (10.3%), conditions due to alcohol use (8.4%), septicemias
      (7.2%) and malnutrition (7.1%). Tuberculosis occurred as an associated cause in
      another 1,388 deaths. The mortality rate including TB as a both underlying and
      associated cause was 8.9/100,000 population, practically twice the classical
      rate. Deaths whose associated cause was reported as being TB had as underlying
      causes: AIDS (65.3%), diseases of the circulatory system (8.9%), neoplasms
      (7.5%), and diseases of the digestive system (4.8%). Clinical forms of nervous
      system and miliary TB were more frequent as a cause associated with AIDS than
      with other underlying causes (p<0,001). CONCLUSIONS: Total reports of TB-related
      death practically doubled its mortality rate as an underlying cause. The increase
      in TB mortality was demonstrated to be influenced by the AIDS epidemic.

PMID- 14666301
TI  - Diptera of sanitary importance associated with composting of biosolids in
      Argentina.
AB  - OBJECTIVE: Odorous compounds produced at the biosolids composting plant in
      Bariloche (NW Patagonia) attract a variety of insects, mainly belonging to the
      order Diptera. In order to characterize these flies, collected specimens were
      taxonomically identified, their community characteristics were described and
      their sanitary and synanthropic importance and autochthonous or introduced
      character were determined. METHODS: Sampling was performed from October 1999
      until March 2000. Adults were collected using an entomological net, and larvae
      and puparia were obtained from the composting material and incubated to obtain
      adults. Richness, abundance and sex ratio were calculated. RESULTS: A total of 9
      taxa of Diptera were identified: Sarconesia chlorogaster, Phaenicia sericata,
      Calliphora vicina, Cochliomya macellaria, Ophyra sp, Muscina stabulans, Musca
      domestica, Sarcophaga sp and Fannia sp. Specimens of Anthomyiidae, Acaliptratae
      and one larva of Eristalis tenax were also found. Ophyra sp. was the most
      abundant taxa. All the captured Diptera belonged to introduced taxa. Most of them
      are considered to be eusynanthropic and/or hemisynanthropic and have sanitary
      importance as they may cause myiasis and pseudomyiasis. The high number of
      females registered and the finding of immature stages indicated that flies can
      develop their complete life cycle on biosolid composting windrows. CONCLUSIONS:
      The characterization of flies obtained in this study may be useful for defining
      locations of urban or semi-urban composting facilities. It also highlights the
      importance of sanitary precautions at such plants.

PMID- 14666302
TI  - [Dominance of Aedes aegypti over Aedes albopictus in the southeastern coast of
      Brazil].
AB  - OBJECTIVE: To assess infestation of Aedes aegypti and Aedes albopiticus and
      describe their association with weather conditions and container colonization in
      urban areas. METHODS: The town of Sao Sebastiao in the southeastern coast of
      Brazil was selected. It was used data from the Dengue and Yellow Fever Vector
      Control Program of the State of S o Paulo, Brazil, that encompasses entomological
      surveillance at strategic positions, traps and foci demarcation. Strategic
      positions sites are fixed sites with containers in adequate conditions for larvae
      growth. Statistical analysis was performed using Kruskal-Wallis test, Dwass-Steel
      Chritchlow-Fligne test and Mann-Whitney test. RESULTS: There was found an annual
      growth of positive traps and strategic positions of Ae. aegypti and a drop in Ae.
      albopictus population. An increase in immature Ae. aegypti and a drop of the
      other species were also seen. A gradual increase of positive dwellings for Ae.
      aegypti was noticed outgrowing Ae. albopictus population. There was a weak
      correlation of the Aedes species with abiotic factors. Higher numbers of immature
      mosquitoes of both species were found in artificial containers which could be
      eliminated. CONCLUSIONS: The study showed Ae. aegypti was predominant in urban
      areas, indicating that its growth seems to have affected the coexistence with
      other species. Natural selection could be in place contributing to Aedes aegypti
      and albopictus species separation.

PMID- 14666303
TI  - [Climacteric syndrome: a population-based study in Campinas, SP, Brazil].
AB  - OBJECTIVES: To study the prevalence of climacteric, urogenital and sexual
      symptoms in a population of Brazilian women. METHODS: A cross-sectional
      descriptive population-based study was conducted. The selection of 456 women aged
      45-60 years, living in Campinas, SP, in 1997, was done through area cluster
      sampling, according to data from the Brazilian Institute of Geography and
      Statistics. Data were collected via home interviews, using structured pretested
      questionnaires. Data were analyzed using the chi-squared test and the
      nonparametric Kruskal-Wallis test; a probability of <0.05 was considered
      statistically significant. The degree of climacteric symptoms was analyzed
      through circulatory and psychological indices. Analysis of the main components
      was used to determine symptom interrelationships. RESULTS: The most prevalent
      symptoms were nervousness (82%), hot flushes (70%), headache (68%), irritability
      (67%) and sweating (59%). Hot flushes, sweating and insomnia were significantly
      more prevalent in the peri and postmenopausal phases. The frequency (severity) of
      vasomotor and psychological symptoms did not vary according to the menopause
      phase. The prevalence of urinary incontinence was 27.4%. Complaints of
      dyspareunia and vaginal dryness were infrequent. Decreased libido was the most
      frequent sexual complaint. It was observed that some climacteric complaints were
      interrelated. The first cluster included hot flushes and sweating (vasomotor
      cluster). The second cluster included nervousness, depression and irritability
      (psychological cluster). The third cluster included dizziness and palpitation
      (atypical cluster). CONCLUSION: Climacteric symptoms in this population were
      highly prevalent and similar to those described in developed Western countries.

PMID- 14666304
TI  - [Hypertension and salt intake in an urban population].
AB  - OBJECTIVE: To evaluate the salt intake and urinary Na+/K+ ratio in a randomized
      sample from an ethnically mixed urban population. METHODS: A randomized
      residential sample of 2,268 individuals aged 25-64 in Vit ria, ES, was selected,
      of whom 1,663 (73.3%) reported to the hospital for standardized tests. Salt, Na+
      and K+ intake was estimated from 12-hour urine excretion (7 p.m. to 7 a.m.) and
      from the monthly salt consumption at home reported in the interview. Clinic
      arterial pressure was measured twice under standard conditions by two trained
      investigators, using mercury sphygmomanometry. The Student t and Tukey tests were
      utilized for statistical analysis. RESULTS: Urinary Na+ excretion was higher in
      men and individuals of lower socioeconomic level (P<0.000). No difference between
      ethnic groups was observed. K+ excretion was unrelated to socioeconomic level and
      ethnicity, but was significantly higher among men (25 18 vs. 22 18 mEq/12h;
      P=0.002). Positive linear correlation was observed between urinary Na+ excretion
      and systolic (r=0.15) and diastolic (r=0.19) arterial pressure. Hypertensive
      individuals showed higher urinary Na+ excretion and Na+/K+ ratio than
      normotensive individuals. Reported salt intake was around 50% of the intake
      estimated from 12-hour urine collection (around 45% of 24-hour urinary
      excretion). CONCLUSIONS: Salt intake is strongly influenced by socioeconomic
      level and may partially explain the higher prevalence of hypertension in lower
      socioeconomic classes.

PMID- 14666305
TI  - [Epidemiological profile of cocaine users on treatment in psychiatrics hospitals,
      Brazil].
AB  - OBJECTIVE: To describe the epidemiological profile and patterns of cocaine use
      among hospitalized drug users. METHODS: A cross-sectional study was carried out
      among drug users, aged 18 years or more, hospitalized in one out six selected
      psychiatric hospitals in the metropolitan area of Greater S o Paulo, whose
      clinical conditions allowed them to reliably answer to a standardized
      questionnaire and who agreed to participate. Six psychiatric hospitals who
      attended spontaneously referred public and private patients from all Greater S o
      Paulo were selected. Data collection was conducted using structured interviews,
      individually applied by a trained psychologist. Statistical analysis was
      performed using Student t-test and Chi-square test at p<0.05. RESULTS: There was
      a predominance of crack use (38.4%) over intravenous drug use (1.6%). Addicts who
      smoked cocaine had lower education, most were unemployed and had previously lived
      on the streets, and used higher amounts of drugs. These addicts also had been
      previously incarcerated more often than addicts who used other routes for drug
      administration. CONCLUSIONS: Drug use is a serious public health problem in
      Greater S o Paulo, and this is shown by the great amount of hospital admissions
      due to drug addiction. Crack users have lower socioeconomic status and more often
      engage in violence and crimes.

PMID- 14666306
TI  - [The potential of central obesity anthropometric indicators as diagnostic tools].
AB  - OBJECTIVE: It has been suggested that the indicators of centralized obesity,
      namely by waist-to-hip circumference ratio (WHR) and waistline measure (WM),
      express different metabolic disorders. Thus, a study was conducted in order to
      verify the diagnostic potential of the relationship between these two measures
      and social, behavioral, and biological determinants of centralized obesity.
      METHODS: Two hierarchical multiple regression models were applied to a 1,042
      subject sample from the city of Sao Paulo, southeastern Brazil, in order to
      evaluate relationships between indicators and determinants for centralized
      obesity. Clinical, biochemical/laboratory, and behavioral surveys were carried
      out using standardized questionnaires. Evaluation included blood pressure,
      anthropometric measurements, and waistline and hip measures. RESULTS: WHR was
      significantly associated with low stature and strongly related to socioeconomic
      level; this was not the case with WM. Both WHR and WM were strongly associated
      with age, sex, and sedentary lifestyle. Women were at greater risk of centralized
      obesity then men: OR=5.04 and 7.27 for WHR and WM, respectively. WHR was
      significantly associated with alterations indicative of metabolic syndrome:
      hypertension and low levels of HDL-cholesterol. WM was significantly associated
      with hypertension alone. Both indicators were strongly associated with the
      concomitant presence of two or more alterations related to metabolic syndrome.
      Unlike WHR, WC was associated with hypercholesterolemia. CONCLUSIONS: WHR was
      more closely associated with socioeconomic factors, former risk of malnutrition,
      and alterations indicative of metabolic syndrome than WM, which was more closely
      associated with risk factors for cardiovascular and arteriosclerotic diseases.

PMID- 14666307
TI  - [Use of statistical process control charts in the epidemiological surveillance of
      nosocomial infections].
AB  - OBJECTIVE: To monitor occurrence trends and identify clusters of nosocomial
      infection (NI) using statistical process control (SPC) charts. METHODS: Between
      January 1998 and December 2000 nosocomial infection occurrence was evaluated in a
      cohort of 460 patients admitted to the Pediatric Intensive Care Unit of a
      university hospital, according to the concepts and criteria proposed by the
      National Nosocomial Infection Surveillance System of the Centers for Disease
      Control, in the United States. Graphs were plotted using Poisson statistical
      distribution, including four horizontal lines: center line (CL), upper warning
      limit (UWL) and upper control limit (UCL). The CL was the arithmetic mean NI rate
      calculated for the studied period; UWL and UCL were drawn at 2 and 3 standard
      deviations above average NI rates, respectively. Clusters were identified when NI
      rates remained above UCL. RESULTS: Mean NI incidence was 20 per 1,000 patient
      days. One urinary tract infection cluster was identified in July 2000, with an
      infection rate of 63 per 1,000 patient days, exceeding UCL and characterizing a
      period of epidemic. CONCLUSIONS: The use of SPC charts for controlling endemic
      levels of NI, through both global and site-specific evaluation, allowed for the
      identification of uncommon variations in NI rates, such as outbreaks and
      epidemics, and for their distinction from the natural variations observed in NI
      occurrence rates, without the need for calculations and hypothesis testing.

PMID- 14666308
TI  - [Microbiological quality of human milk from a Brazilian milk bank].
AB  - OBJECTIVE: The objectives of the present study were to determine the prevalence
      of potentially pathogenic microorganisms that indicate the hygienic and sanitary
      conditions of human milk samples collected at a Human Milk Bank. METHODS: Three
      hundred and thirty eight (338) samples of human milk collected from a milk bank
      in a maternity in the municipality of Goiania, in the state of Goias, Brazil were
      submitted to microbiological analysis. The latter were plated on McConkey agar
      according to the type of bacteria. Among the total number of samples collected,
      194 consisted of raw milk and the remaining 144 were pasteurized milk. RESULTS:
      The presence of Staphylococcus spp., Streptococcus spp., yeasts and molds, and
      Enterobacteriaceae was verified in the raw milk samples. Staphylococcus aureus
      were isolated in 10 (5.2%) samples, Staphylococcus epidermidis in 28 (14.4%)
      samples, Streptococcus spp. in three (1.6%) samples, yeasts and molds in 43
      (22.2%) and Enterobacteriaceae in 49 (25.3%) samples. In a hundred and forty four
      (144) samples which underwent thermal treatment Staphylococcus aureus was
      detected in five (3.5%) samples, Staphylococcus epidermidis in 15 (10.4%),
      Staphylococcus lugdenensis in two (1.4%), Streptococcus spp. in four (2.8%),
      yeasts and molds in 37 (25.7%), and Enterobacteriaceae in nine (6.3%).
      CONCLUSIONS: Analysis indicated a high degree of contamination in raw human milk,
      and as for the pasteurized milk, despite elimination of the great majority of
      potentially pathogenic microorganisms, the percentage of yeasts and molds was
      higher than in raw milk, demonstrating that a lower degree of initial
      contamination would be necessary for pasteurization to be an efficient means of
      microbiological control.

PMID- 14666309
TI  - [Assessment of urinary trans, trans-muconic acid as a biomarker of exposure to
      benzene].
AB  - OBJECTIVE: To assess the use of trans, trans-muconic acid as a biomarker of
      occupational exposure to benzene. METHODS: Trans, trans-muconic acid in urine
      samples of exposed (exposed group, n=36) and non-exposed (non-exposed group,
      n=116) workers to benzene. Urinary levels of trans, trans-muconic acid were
      quantified by high-performance liquid chromatography. The study sample consisted
      of subjects exposed to benzene in an oil refinery in Belo Horizonte, Brazil. Non
      parametric statistical analysis was carried out using Kruskall-Wallis test, Mann
      Whitney test and Spearman correlation at p<0.05. RESULTS: Workers were exposed on
      average to benzene levels of 0.15 +/- 0.05 mg/m3 (0.05 ppm) and they showed a
      urinary trans, trans-muconic acid mean value of 0.19 +/- 0.04 mg/g of creatinine.
      The reference value range of trans, trans-muconic acid in non-exposed subjects
      was 0.03 to 0.26 mg/g of creatinine (mean 0.10 +/- 0.08 mg/g of creatinine).
      There was seen a statistical difference between trans, trans-muconic acid levels
      in urine samples from exposed and non-exposed groups. There was no correlation
      between urinary trans, trans-muconic acid and air benzene levels. There was no
      correlation between urinary trans, trans-muconic acid levels in the exposed group
      and smoking. Alcohol consumption up to 48 hours before sampling procedure showed
      no effect on trans, trans-muconic acid levels in both exposed and non-exposed
      groups. There was however a correlation between age (range 18 to 25 years) and
      urinary metabolite levels in the latter group. CONCLUSIONS: The results show that
      it is important to evaluate the effect of age and smoking habits on urinary
      trans, trans-muconic acid levels.

PMID- 14666310
TI  - [Dental anxiety in an emergency dental service].
AB  - OBJECTIVE: The purpose of the study was to assess the frequency of dental anxiety
      and/or fear among patients in an emergency dental service. METHODS: Research was
      based on interviews with 252 patients, aged 18 years old and over, attended at an
      emergency dentistry service of Sao Paulo, Brazil, from August to November, 2001.
      Two methods were used to measure dental anxiety: the Modified Dental Anxiety
      Scale (MDAS) and the Gatchel Fear Scale. The study group answered questions
      concerning major complaint, how much time had elapsed since their last visit to
      the dentist and since the initial symptoms leading to the current visit to the
      emergency service, level of education, family income and previous traumas.
      Statistical analysis (chi2 and Fisher exact test) was performed to evaluate these
      characteristics. RESULTS: It was found that 28.17% of this sample was dentally
      anxious, according to the MDAS, and 14.29%, felt fear related to dental treatment
      according to the Gatchel Fear Scale. Women were more anxious than men at a
      statistically significant rate (MDAS). The time elapsed since the onset of
      initial symptoms was more than 7 days for 44.44% of the participants. A large
      proportion of anxious women returned to treatment during the last year. A
      previous traumatic experience with dental was identified in 46.48% of the
      dentally anxious patients. No significant relation between level of education or
      income and dental anxiety was found. CONCLUSIONS: Dentally anxious patients
      frequent attend emergency care. Females are more likely to report high dental
      anxiety than males. Previous experience seems to be an important factor
      contributing to avoidance of dental care.

PMID- 14666311
TI  - [WHOQOL-OLD Project: method and focus group results in Brazil].
AB  - OBJECTIVES: Exploring the conditions that allow satisfactory quality of life in
      old age is an issue of scientific and social relevance. Thus, the objective of
      the study was to describe a quality of life assessment method for the elderly and
      present the results from focus groups conducted among old people in good health
      and ill health, as well as their caregivers. METHODS: The methodology used in the
      WHOQOL-OLD project is the same as utilized in the development of other WHOQOL
      modules. Five focus groups were conducted in Brazil. The sampling procedure was
      done according to convenience. Eighteen old people and five caregivers took part
      in the focus groups. All the focus groups followed a pre-established methodology.
      RESULTS: A tendency towards making an association between quality of life and
      wellbeing and feeling well was observed. The responses spontaneously included the
      6 domains proposed in WHOQOL-100, thus corroborating the multidimensional nature
      of this construction. Nineteen out of the 24 original facets of this instrument
      were cited as relevant, and the five facets not spontaneously remembered were not
      concentrated in a single domain. When questioned about the importance of each of
      the 24 facets of WHOQOL-100, the groups considered all of them to be relevant.
      However, suggestions for modifications to five facets were made. Additional items
      were also examined and considered relevant for assessing quality of life among
      the elderly, by both the old people and the caregivers. CONCLUSIONS: The results
      corroborate the hypothesis that old people constitute a particular group and, as
      such, they have relevant specific characteristics. Thus, an appropriate
      instrument for assessing quality of life among the elderly needs to consider such
      matters.

PMID- 14666312
TI  - [Software program to systematize data for planning public health actions].
AB  - OBJECTIVE: To describe and evaluate a software program to provide basic health
      care teams with primary health services data. METHODS: It was described the
      PACOTAPS (software program for primary health care), developed using Visual Basic
      5.0, and secondary data and outpatient care demand modules were tested in a basic
      health care unit in Pelotas, Brazil. Age/gender structure of the reference
      population was obtained from secondary data. Outpatient care demand allowed the
      characterization of all 4,170 visits carried out in a month by analyzing
      Outpatient Care Files. RESULTS: Age and gender distribution as well as main
      diagnoses and referrals were identified for all patients seen at the health care
      unit. In addition, there were detected differences among the health care centers
      due to either different organization and care models or as a result of different
      actual needs of improvement in patient register systems. CONCLUSIONS: PACOTAPS, a
      user-friendly software program, can contribute to health care unit management
      evaluation within the national Unified Health System (SUS). The availability of
      an electronic tool combining resources allows decision making in healthcare
      facilities, and even at municipal health policy level, to be based on more
      adequate and effective data.

PMID- 14666313
TI  - Trypanosoma cruzi prevalence and clinical forms in blood donor candidates in
      Brazil.
AB  - The prevalence and clinical forms of Trypanosoma cruzi were evaluated among blood
      donor candidates attended at a general hospital in Rio de Janeiro, Brazil, from
      January 1997 to April 1999. The investigation was done by means of the indirect
      hemagglutination test and was confirmed via ELISA. Data were collected from
      clinical examinations, conventional electrocardiogram, chest radiography and
      echocardiography. The results showed that despite Trypanosoma cruzi prevalence of
      1.17% (128 patients), mainly in males aged 40 years or over, 70.8% of these
      patients, mainly males aged 19 to 39 years, demonstrated abnormalities that
      allowed the diagnosis of cardiopathy and/or esophagopathy. This once again
      corroborates the importance of Trypanosoma cruzi infection in urban centers.

PMID- 14666314
TI  - [Microhimenopteran parasitoids of Chrysomya megacephala found in Brazil].
AB  - The study was carried out with the purpose of identifying the main parasitoids of
      Chrysomya megacephala in the city of Rio de Janeiro, Brazil, given the importance
      of these flies as vectors of pathogenic agents in the urban environment.
      Samplings were conducted every week from August 1999 to July 2000. The substrate
      used to grow fly pupae and to trap parasitoids was decomposing meat. It was
      identified three species of microhimenopterans: Tachinaephagus zealandicus
      (Encyrtidae), Pachycrepoideus vindemiae (Pteromalidae) and Nasonia vitripennis
      (Pteromalidae). Further analysis will be performed in order to show the potential
      of these insects as agents in biological control programs.

PMID- 14666315
TI  - [Potential of Bacillus thuringiensis israelensis Berliner for controlling Aedes
      aegypti].
AB  - The importance of the entomopathogenic bacterium Bacillus thuringiensis
      israelensis in the control of Aedes aegypti is presented. The use and potential
      of B. thuringiensis israelensis against the mosquito vector of dengue fever is
      described. Other aspects such as insect's resistance development against
      chemicals and advantages and constraints of using microbial control are
      discussed. Emphasis is given to the importance of the use of this bacterium in
      Brazil, which could contribute significantly to solving the mosquito problem
      without affecting the environment, humans and others invertebrate organisms in
      critical regions.

PMID- 14666316
TI  - [Chickenpox, diphtheria and Brazilian rickettsial disease: epidemiology of the
      state of Sao Paulo].

PMID- 14666317
TI  - [Actions for increasing drug quality, safety and efficacy].

PMID- 14666319
TI  - Maternal immunization: safe and effective.

PMID- 14666320
TI  - Laparoscopic versus open splenectomy in the management of hematologic diseases.
AB  - Splenectomy is the best available treatment for severe forms of hereditary
      spherocytosis, idiopathic thrombocytopenic purpura, and other hematologic
      conditions when these prove refractory to conservative management. It has been
      employed for many decades with low mortality and favorable remission rates. The
      use of laparoscopic splenectomy in recent years has been rapidly and even
      enthusiastically adopted in this field. However, the exact role of laparoscopic
      versus open surgery for hematologic diseases is still debated. In this study of
      58 adult patients, laparoscopic procedures were compared with conventional
      splenectomies for similar indications. METHODS: All patients were operated on
      within an 8-year period. Subjects underwent similar procedures under the
      supervision of the same surgical school and were compared regarding age, gender,
      body mass index, and diagnosis. Laparoscopically managed cases (Group I, n = 30)
      were prospectively followed according to a written protocol, whereas the same
      investigation was retrospectively done with regard to traditional laparotomy
      (Group II, n = 28). Methods included general and demographic findings, duration
      and technical steps of operation, blood loss, weight of spleen, need for
      conversion (in minimally invasive subjects), intraoperative and postoperative
      complications, time until realimentation, postoperative hospitalization,
      mortality, and late follow-up including recurrence rate. RESULTS: Idiopathic
      thrombocytopenic purpura was the surgical indication in over 50% of the patients
      in both groups, but familial spherocytosis, thalassemia, myelodysplasia, and
      lymphomas were also represented in this series. Laparoscopic procedures took more
      time to perform (P = 0.004), and postoperative hospitalization was 2 days
      shorter, but this difference was not statistically significant. Postoperative
      hematocrit and volume of blood transfusions was equivalent, although the
      laparoscopic cases had a somewhat lower preoperative hematocrit (NS) and
      displayed better recovery for this measurement (P = 0.03). More patients in Group
      I were able to accept oral food on the first day than subjects undergoing
      conventional operations (P < 0.05). Relatively few conversions were necessary
      during the minimally invasive surgeries (13.3%), and postoperative early and late
      complications as well as recurrences occurred in similar proportions. Also, the
      mean weight of the spleen was not statistically different between the groups,
      although there was a marked numerical tendency toward larger masses in
      conventional procedures. No spleen in Group I exceeded 2.0 kg, whereas in Group
      II values up to 4.0 kg occurred, and the mean weight was 50% higher in the latter
      group. CONCLUSIONS: 1) Minimally invasive splenectomy was essentially comparable
      to open surgery with regard to safety, efficacy, and late results; 2) Advantages
      concerning shorter postoperative hospitalization could not be shown, despite
      earlier food intake and a non-significant tendency toward earlier discharge; 3)
      This new modality should be considered an option in cases of hematologic
      conditions whenever the spleen is not hugely enlarged.

PMID- 14666321
TI  - Sperm tail flexibility test: a simple test for selecting viable spermatozoa for
      intracytoplasmic sperm injection from semen samples without motile spermatozoa.
AB  - PURPOSE: The objective was to describe the results of the injection of immotile
      spermatozoa with flexible tails when only immotile spermatozoa are present in the
      semen sample. METHODS: A retrospective study was conducted to analyze the
      procedure results for 10 couples who participated in our intracytoplasmic sperm
      injection program. The sperm tail was considered flexible when it moved up and
      down independently of the head movement, and it was considered inflexible when
      the movement occurred together (tail plus head). The fertilization and pregnancy
      rate were analyzed. RESULTS: The normal fertilization rate (presence of 2
      pronuclei) was 30.3% (40/132), and the abnormal fertilization rate (presence of
      less than or more than 2 pronuclei) was 6.81% (9/132). A total of 52 embryos were
      obtained with 9 transfer procedures performed (pregnancy rate: 11.12%).
      CONCLUSIONS: The sperm tail flexibility test (STFT) is an easy and cost-effective
      way for selecting viable immotile spermatozoa and can be used as an alternative
      method for determining the viability of spermatozoa. This test seems to be a
      simple and risk-free method when compared to the swelling test.

PMID- 14666322
TI  - Prevalence rates of infection in intensive care units of a tertiary teaching
      hospital.
AB  - OBJECTIVE: To determine the prevalence rates of infections among intensive care
      unit patients, the predominant infecting organisms, and their resistance
      patterns. To identify the related factors for intensive care unit-acquired
      infection and mortality rates. DESIGN: A 1-day point-prevalence study. SETTING: A
      total of 19 intensive care units at the Hospital das Clinicas-University of Sao
      Paulo, School of Medicine (HC-FMUSP), a teaching and tertiary hospital, were
      eligible to participate in the study. PATIENTS: All patients over 16 years old
      occupying an intensive care unit bed over a 24-hour period. The 19 intensive care
      unit s provided 126 patient case reports. MAIN OUTCOME MEASURES: Rates of
      infection, antimicrobial use, microbiological isolates resistance patterns,
      potential related factors for intensive care unit-acquired infection, and death
      rates. RESULTS: A total of 126 patients were studied. Eighty-seven patients (69%)
      received antimicrobials on the day of study, 72 (57%) for treatment, and 15 (12%)
      for prophylaxis. Community-acquired infection occurred in 15 patients (20.8%),
      non-intensive care unit nosocomial infection in 24 (33.3%), and intensive care
      unit-acquired infection in 22 patients (30.6%). Eleven patients (15.3%) had no
      defined type. The most frequently reported infections were respiratory (58.5%).
      The most frequently isolated bacteria were Enterobacteriaceae (33.8%),
      Pseudomonas aeruginosa (26.4%), and Staphylococcus aureus (16.9%; [100% resistant
      to methicillin]). Multivariate regression analysis revealed 3 risk factors for
      intensive care unit-acquired infection: age > or = 60 years (p = 0.007), use of a
      nasogastric tube (p = 0.017), and postoperative status (p = 0.017). At the end of
      4 weeks, overall mortality was 28.8%. Patients with infection had a mortality
      rate of 34.7%. There was no difference between mortality rates for infected and
      noninfected patients (p = 0.088). CONCLUSION: The rate of nosocomial infection is
      high in intensive care unit patients, especially for respiratory infections. The
      predominant bacteria were Enterobacteriaceae, Pseudomonas aeruginosa, and
      Staphylococcus aureus (resistant organisms). Factors such as nasogastric
      intubation, postoperative status, and age 60 years were significantly associated
      with infection. This study documents the clinical impression that prevalence
      rates of intensive care unit-acquired infections are high and suggests that
      preventive measures are important for reducing the occurrence of infection in
      critically ill patients.

PMID- 14666323
TI  - Cystic fibrosis with normal sweat chloride concentration--case report.
AB  - Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing.
      We report a case of an 18-year-old female with bronchiectasis, chronic P.
      aeruginosa infection, and normal sweat chloride concentrations who experienced
      rapid decrease of lung function and clinical deterioration despite treatment.
      Given the high suspicion of cystic fibrosis, broad genotyping testing was
      performed, showing a compound heterozygous with deltaF508 and 3849+10 kb C-->T
      mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat
      chloride test remains the gold standard for the diagnosis of cystic fibrosis,
      alternative diagnostic tests such as genotyping and electrophysiologic
      measurements must be performed if there is suspicion of cystic fibrosis, despite
      normal or borderline sweat chloride levels.

PMID- 14666324
TI  - Vaccines in pregnancy: a review of their importance in Brazil.
AB  - Neonates and young children remain susceptible to many serious infectious
      diseases preventable through vaccination. In general, current vaccines strategies
      to prevent infectious diseases are unable to induce protective levels of
      antibodies in the first 6 months of life. Women vaccinated during pregnancy are
      capable of producing immunoglobulin antibodies that are transported actively to
      the fetus, and maternal immunization can benefit both the mother and the child.
      With few exceptions, maternal immunization is not a routine, because of the
      concerns related to the safety of this intervention. Ethical and cultural issues
      make the studies on maternal immunization difficult; however, in the last decade,
      the development of new vaccines, which are very immunogenic and safe has
      reactivated the discussions on maternal immunization. In this paper we present a
      review of the literature about maternal immunization based on MEDLINE data (1990
      to 2002). The most important conclusions are: 1) there is no evidence of risk to
      the fetus by immunizing pregnant women with toxoids, polysaccharide,
      polysaccharide conjugated and inactive viral vaccines; 2) most viral attenuated
      vaccines are probably safe too, but data is still insufficient to demonstrate
      their safety; therefore these vaccines should be avoided in pregnant women; 3) in
      Brazil, there is a need for a maternal immunization program against tetanus. Many
      new candidate vaccines for maternal immunization are available, but studies
      should be conducted to evaluate their safety and efficacy, as well as regional
      priorities based on epidemiological data.

PMID- 14666325
TI  - Trends in male contraception.
AB  - Methods that are available for male contraception, namely coitus interruptus,
      condoms, and vasectomy, have been used since the 19th century. With the
      exceptions of a few improvements of these methods, no major progress has been
      made with respect to introducing new male contraceptives since then. It is
      extremely urgent to develop new, safe, effective, and reversible male
      contraceptive methods. Among all male contraceptive methods that are being
      investigated, the hormonal approach is the closest to clinical application.
      Hormonal contraception provides pregnancy protection by means of spermatogenic
      suppression. Androgen-progestin regimens currently represent the best available
      hormonal combination for induction of a profound suppression of spermatogenesis.
      Further development of new steroids is mandatory for increasing the choices of
      available contraceptive formulations and to optimize long-term safety of these
      regimens.

PMID- 14666326
TI  - Conservative therapies for hemorrhagic radiation proctitis: a review.
AB  - Chronic radiation proctitis represents a challenging condition seen with
      increased frequency due to the common use of radiation for treatment of pelvic
      cancer. Hemorrhagic radiation proctitis represents the most feared complication
      of chronic radiation proctitis. There is no consensus for the management of this
      condition despite the great number of clinical approaches and techniques that
      have been employed. Rectal resection represents an available option although
      associated with high morbidity and risk of permanent colostomy. The effectiveness
      of nonoperative approaches remains far from desirable, and hemorrhagic recurrence
      represents a major drawback that leads to a need for consecutive therapeutic
      sessions and combination of techniques. We conducted a critical review of
      published reports regarding conservative management of hemorrhagic chronic
      radiation proctitis. Although prospective randomized trials about hemorrhagic
      radiation proctitis are still lacking, there is enough evidence to conclude that
      topical formalin therapy and an endoscopic approach delivering an argon plasma
      coagulation represent available options associated with elevated effectiveness
      for interruption of rectal bleeding in patients with chronic radiation proctitis.

PMID- 14666327
TI  - [Emergency Medicine in Brazil: where are we going?].

PMID- 14666333
TI  - [Recombinant human activated protein C for sepsis: When should it be indicated?].

PMID- 14666342
TI  - [Knowledge on screening and diagnosis of breast cancer among gynecologists in
      Goias State (Brazil].

PMID- 14666343
TI  - [Round pneumonia with pseudotumoral pneumonia].

PMID- 14666344
TI  - [Metastasis of endovascular angioendothelioma to clitoris and breast].

PMID- 14666346
TI  - [Quality of life in chronic renal disease patients submitted to hemodialysis
      evaluated with SF-36 instrument].
AB  - Quality of life is a new concept in the health area and controversies exist about
      its application to clinical practice. Studies carried out in Brazil in the
      nephrology area have indicated the need for further investigations. OBJECTIVE: To
      analyze the quality of life of patients with different times of hemodialysis.
      METHODS: The study consisted of application of the questionnare SF-36, collection
      of demographic, socioeconomic and biochemical data, as well as of the clinical
      characteristics. RESULTS: The study was conducted on 184 patients, 63% of them
      males, aged 46 15 years (X SD), with a hemodialysis time of 30 36 months; 48% had
      up to 4 years of schooling and 53% belonged to the economic-social classes D and
      E. Impairment of the different dimensions analyzed was observed, with the poorest
      results being obtained for Physical Aspects and Vitality. A negative correlation
      was detected between Age and Functional Capacity, Physical Aspects, Pain, and
      Vitality, and between Hemodialysis Time and Emotional Aspects. A positive
      correlation was observed between Schooling and Emotional Aspects and between
      Hemoglobin and Vitality. We observed that diabetic patients were older than non
      diabetic patients and presented lower values for the Functional Capacity and
      General Health condition dimensions. CONCLUSION: SF-36 proved to be a good
      instrument for the assessment of the quality of life of hemodialysis patients.
      The presence of a chronic disease, the need for continuous treatment over a long
      period of time, advanced age, and the presence of co-morbidities were factors
      that might interfere with the quality of life of this population.

PMID- 14666347
TI  - [Extraprostatic disease prediction in patients with carcinoma of the prostate:
      role of PSA, prostatic biopsy fragments percentage and Gleason score].
AB  - OBJECTIVE: To valuate the behavior of the prostatic biopsy fragments percentage,
      guided by transrectal ultrasonography in extraprostatic disease prediction in
      patients with localized adenocarcinoma of the prostate gland and, also, to
      compare the efficiency of this pattern with them got by the valuation of PSA and
      preoperative Gleason score. METHODS: This retrospective non-controlled study
      consisted of 522 patients with adenocarcinoma located in the prostate. They were
      submitted to surgical treatment through retropubic radical prostatectomy. The
      ages of the patients ranged from 42 to 76 years with a mean of 62.44 years. All
      of them were submitted to transrectal ultrasonography with prostatic biopsy
      (direct of the lesion and/or suspected area and sextant) previous to the radical
      surgical treatment. The 522 patients were divided in groups according to the
      positive fragments found by the biopsy, what was correlated with the
      anatomicpathologic findings of intraprostatic disease (limited to the gland) and
      extraprostatic (invasion periprostatic adiposity and/or the bladder neck and/or
      the seminal vesicles and/or positive pelvic lymph nodes) of the surgical
      specimen. RESULTS: Regarding the analysis of the positive fragments percentage,
      the groups G1 (0-25%), G2 (20-50%) and G3 (51-75%) showed an incidence of the
      intraprostatic disease two and three times greater than the extraprostatic one.
      However, when more than 75% of the biopsy fragments were positive (G4, 76-100%),
      the relation inverted occurring a predominance of the extraprostatic disease over
      the intraprostatic. In this group 56.98% of the patients showed extraprostatic
      disease. There was a statistically significant difference of the extraprostatic
      disease between the groups G3 and G4 (p 0.0068). CONCLUSION: When we compared the
      three inconstant to evaluate the efficiency order anticipating extraprostatic
      disease, we verified that the preoperative PSA was the most discriminated (p =
      0.000000) followed by the Gleason score of prostatic biopsy (p = 0.000003) and by
      the positive biopsies percentage (p = 0.000574).

PMID- 14666348
TI  - [Direct mean cost of the material used in coronary artery bypass graft surgery].
AB  - PURPOSE: To verify the direct average cost of the material used in the Coronary
      Artery Bypass Graft (CABG) Surgery and to compare the average cost according to
      the number of bypasses perfomed (arterial and veins grafts). METHODS: This is a
      descriptive study conducted in a Cardiac Surgery Center in S o Paulo city. The
      sample includes 104 procedures for CABG surgery with extracorporeal circulation.
      The information was collected by a standard printed torn containing the material.
      RESULTS: The analyses of the information showed that the direct mean cost of the
      material used in the surgery was R$2.718,78. CONCLUSIONS: A variation of material
      costs was observed proportional to the increase in number of bypasses
      performance, showing a statistical significant difference among surgerical
      interventions with 1, 2 and 3 cal bypasses which was not observed in surgeries
      with 3, 4 and 5 bypases. The direct mean cost was: CABG with 1 bypass
      (R$2.207,71), 2 (R$2.554,61), 3 (R$2.768,94), 4 (R$2.848,65) and 5 (R$2.884,13).
      The items of the perfusion material (R$1.051,24), surgical threads (R$829,98) and
      consumption material (R$442,40), represented those with a higher mean cost.

PMID- 14666349
TI  - [Accidental hypothermia cases in a tropical country].
AB  - OBJECTIVE: This paper has by objective to study the hypothermia's presence,
      presentation form and consequences in our environment. METHODS: A prospective
      study in hypothermic patients assisted in the Medical Clinic Emergency Service of
      Santa Casa of S o Paulo, with 212 patients with mild, moderate and serious
      hypothermia from 1987 to 2001, the most part of them constituted by chronic
      alcoholics and homeless. The results were analyzed in reference to sex, age
      group, central temperature, electrocardiogram, co-morbidity and mortality.
      RESULTS: The hypothermia prevailed in the male sex with 75.9%. As age group
      prevailed the age between 30 and 59 years. In 70.3% of the patients the central
      temperature went lower than 32 C, and in 26.4% of these, the temperature was
      lower than 28 C. The association with infectious processes happened in 76.8% of
      the cases. The patients with mild hypothermia answered better at therapeutics
      (96.8%) when compared with the moderate hypothermic (72.1%) and serious (87.5%)
      patients. The Osborn's wave was present in 42.6% of the patients. The general
      mortality was 38.2%. CONCLUSIONS: The accidental hypothermia in Emergency
      Services from Tropical Country is an undeniable fact. The paramedic and medics
      should be alert and trained to recognize this disease of high morbidity and
      mortality. The mortality increases with the presence of associated diseases,
      particularly infectious processes, malnutrition and chronic alcoholism.

PMID- 14666350
TI  - [Number of years on chronic dialysis and the mortality risk in patients with and
      without diabetes mellitus].
AB  - OBJECTIVE: To assess whether, in Brazil, the number of years on dialysis
      treatment in end-stage renal disease (ESRD) patients, with and without diabetes
      mellitus, relates to mortality risk. METHODS: Analysis of data from the Ministry
      of Health of Brazil of 25.952 patients older than 18 years who were on dialytic
      treatment in April 1997. Death cases that occurred from April 1997 to July 2000
      were recorded. Cox models were used to estimate the relative risk (RR) of the
      association between years on dialysis and mortality risk. RESULTS: The mortality
      risk was significantly lower in patients on dialysis between 3 and <10 years as
      compared with 1 to <2 years (RR between 0.78 and 0.88). With adjustments for age
      and diabetes the effect of years on dialysis was reduced. In diabetics (n=2.952)
      the adjusted mortality risk showed a trend to decrease with more years on
      dialysis. CONCLUSIONS: In Brazil, the mortality risk for ESRD patients decreases
      with the increasing number of years on dialysis up to approximately 10 years.
      This finding can be partially explained by the lower mean age and prevalence of
      diabetes mellitus in patients with more years on dialysis treatment. The effect
      of years on dialysis on the mortality risk seems to be stronger in patients with
      diabetes.

PMID- 14666351
TI  - [Airborne fungi and sensitization in atopic individuals in Porto Alegre, RS,
      Brazil].
AB  - OBJECTIVE: To identify and quantify the fungal spores in the atmospheric air of
      Porto Alegre and to assess sensitization to these allergens in atopic individuals
      suffering from rhinitis and asthma. METHODS: A total of 52 samples were obtained
      using a Rotorod Sampler  from April 2000 through March 20001. Allergy skin tests
      with anemophilous fungus allergens as well as fluorimmunoenzymatic tests were
      performed in 39 atopic individuals with rhinitis and asthma in order to detect
      the incidence of respiratory allergies caused by these airborne fungi. RESULTS:
      In the 3773 fungal spores detected in this study, there was a prevalence of
      ascosporos (50.49%), Cladosporium (17.86%), Aspergillus/Penicillium (15.03%),
      basidiosporos (3.84%), rusts (3.82%), and Helminthosporium (2.49%), as well as a
      lesser frequency of Botrytis (1.22%), Alternaria (1.19%), smuts (0.90%),
      Curvularia (0.87%), Nigrospora (0.61%), and Fusarium (0.08%). Sixty spores
      (1.59%) detected here could not be identified by the systematic key used. Among
      the atopic individuals tested, 15.38% were found to be sensitized by these
      anemophilous fungi allergens. CONCLUSIONS: The occurrence of a great number of
      fungal spores emphasizes the importance of studying anemophilous fungi locally,
      since they are responsible for 15.38% of allergic sensitization in atopic
      individuals with asthma and rhinitis.

PMID- 14666352
TI  - [Lung volume reduction surgery (LVRS): criteria for selecting patient in Antonio
      Pedro Hospital, Federal Fluminense University, Niter i city, Rio de Janeiro,
      Brazil].
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (CPOD) is an important problem
      in Brazil and other countries. The clinical treatment of ambulatory patients is
      now reasonably standardized. Lung volume reduction surgery (LVRS) is an
      alternative of surgical treatment of emphysema (aside from lung transplantation).
      OBJECTIVES: The aim of this study was to analyse patient selection criteria for
      LVRS. METHODS: This study was carried out using a sample of 31 patients referred
      to and given assistance to at the Smoking and Chronic Obstructive Pulmonary
      Disease Outpatient Ward Antonio Pedro Hospital, who were evaluated to check
      whether or not they could be eligible for LVRS. Aiming at evaluating the major
      criteria for eligibility for LVRS, the patients underwent a protocol including
      standardized anamnesis and physical examination, spirometry with maximum
      inspiratory and expiratory flow volume curves associated with post
      bronchodilatator test, room air arterial blood gases, a six-minute walking test,
      plain chest roentgenograms and left lateral chest roentgenograms, high-resolution
      chest computed tomographic scans and lung perfusion scans. Statistical analysis
      was conducted with description of data proportions. RESULTS: Contraindications to
      surgery included chronic bronchitis (29% or nine patients), forced expiratory
      volume in one second (FEV 1) more than 80 percent predicted (13% or four
      patients), negative consent for surgery (10% or three patients), fibrosis
      pattern, severe depression and bronchiectasis (two patients each one), solitary
      pulmonary nodule, severe obesity, severe bullous emphysema, pulmonary
      hipertension, pulmonary resection history, current cigarette smoking, diffuse
      emphysema with alpha-1-antitrypsin deficiency and severe cardiac disease (one
      patient each). Indication. One selected patient with severe symptoms of emphysema
      met criteria for LVRS (bilateral superior lobe heterogeneous pattern of emphysema
      on chest computed tomography and lung perfusion scan). CONCLUSIONS: Chronic
      bronchitis was the major isolated factor to contraindicate LVRS. Most patients
      who fit the criteria for the surgery performance refused to undergo the LVRS for
      fear of the surgery and after pulmonary rehabilitation. The most important
      criteria for LVRS is bilateral superior lobe heterogeneous pattern of emphysema.

PMID- 14666353
TI  - [The functional evaluation of dysphagia in the neonatal intensive care unit].
AB  - BACKGROUND: The objectives of this study were: 1) to detect clinical criteria on
      the evaluation of dysphagy in preterm newborns; 2) to analyze the association
      between the functional and the videoendoscopy findings and 3) to show the
      relevance of the joint work of the Speech Therapist and the Otolaryngologist
      criteria on the evaluation of dysphagy in preterm syndromic and pathologic
      newborns. METHODS: The sample comprised fifteen infants born in Maternity
      Campinas Hospital, Campinas-SP, to whom was requested a Speech Therapist
      evaluation by the Neonatologist. All the infants were evaluated once by the same
      Speech Therapist and the Otolaryngologist. The functional evaluation of
      swallowing considered: a) the extra oral tactile sensibility, b) the intra oral
      tactile sensibility, c) the nauseous reflex and d) the buccinator movement. The
      evaluation of the videoendoscopy swallowing analyzed a) the sensibility in the
      arytenoid cartilage, b) the crying, c) the aspiration, d) desaturation and e) the
      penetration. The exact test of Fisher was applied for small samples and each
      hypothesis was tested with significance level of 0.05. RESULTS: At the end of the
      study, a statistically dependence relation between the variants was noticed: 1)
      aspiration after pharyngeal phase and penetration (high and low) and 2) extra
      oral sensibility on the cheeks and the sensibility on the arytenoid cartilage.
      CONCLUSION: This last result shows the association between a functional finding
      obtained by the Speech Therapist and a videoendoscopy finding achieved by the
      Otolaryngologist, that shows clearly the relevance of the team work among these
      two health professionals.

PMID- 14666354
TI  - [Use of corticosteroids after esophageal dilations on patients with corrosive
      stenosis: prospective, randomized and double-blind study].
AB  - OBJECTIVE: To determine triancinolone intralesional injections effects in
      association with esophageal dilations in corrosive stenosis cases, by means of a
      double-blind and randomized study. METHOD: Fourteen adults patients (6 men and 8
      women) with severe esophageal corrosive stenosis were randomized in two groups:
      Group A: treated by esophageal dilations and posterior triancinolone 10 mg/ml
      intralesional injection; Group B: treated by esophageal injections and posterior
      saline solution 0,9% injection (placebo). New applications were made based on the
      patient symptomatology. It had been analysed dilation frequency, obtained
      diameters and dysphagia before and after the research, for 12 months. RESULTS:
      Eleven patients had ingested sodium hydroxide, two had ingested ammoniac and one
      had taken muriatic acid. There was no statistic difference (p > 0.05) in dilation
      frequency and dysphagia between the groups. However, an improvement in obtained
      diameter was observed in the corticosteroids group in comparison with control
      group (p < 0.05). By comparing groups before and after steroids, the final
      results were very favorable in group A CONCLUSION: Multiple intralesional
      injections of triancinolone hexacetonide 10 mg/ml in association with esophageal
      dilations increase obtained diameters in succeeding sessions.

PMID- 14666355
TI  - [Cholecystectomy in the elderly: early results of open versus laparoscopic
      approach].
AB  - The rise of elderly population is due to the improvement of life expectancy. The
      biliary lithiasis is the most common condition requiring intra-abdominal surgery.
      Half of these patients sustain associated diseases and frequently develops acute
      and complicated forms of cholelithiasis. Therefore, cholecystectomy is indicated
      for patients with chronic symptomatic disease. During a long period open
      cholecystectomy has been practiced, with low complications and mortality rates.
      Videolaparoscopy has been recently proposed as an option in these cases, however,
      few studies compared its advantages over open cholecystectomy for elderly
      patients. OBJECTIVE: To access the early results of the surgical treatment for
      cholelithiasis in the elderly submitted to an open or laparoscopic
      cholecystectomy. METHODS: retrospective study with 246 patients > 65 years old,
      who underwent elective cholecystectomy through a subcostal incision (group I) or
      laparoscopic approach (group II). We employed Student's t test and Spearman's
      correlation for statistical analysis, considering p < 0,05 as significant.
      RESULTS: A hundred and twenty patients were arranged in group I and 126 in group
      II. Associated diseases were present in 155 cases (63). There were no differences
      between the groups regarding both the distribution of comorbid conditions.
      Conversion was evaluated in 10 patients (8.3%). The mean operative time was 133
      minutes in group I and 112 minutes in group II (p=0.001). The mean hospital stay
      in group I was 3,3 days and in group II was 3.2 days p=0.698. Thirteen patients
      in each group developed complications: group I (10.8%) and group II (10.3%)
      p=0,896. There was no statistis significance in complication rate related to
      gender, age, associated diseases and ASA when the both groups were compared.
      There were two deaths, both in group II, although the mortality rate was not
      statiscally significant between the groups (p=0.158). CONCLUSION: Both open and
      laparoscopic cholecystectomy can be practiced in the elderly with low and similar
      rate of complications.

PMID- 14666356
TI  - [Influence of neoadjuvant treatment on morbidity-mortality of esophagectomies].
AB  - BACKGROUND: To evaluate the influence of neoadjuvant treatment (chemotherapy
      and/or radiotherapy) on postoperative complications and hospital lethality in
      patients with esophageal cancer submitted to esophagectomy with two-field
      lymphadenectomy. METHODS: Retrospective study of 132 patients with esophageal
      cancer admitted in Department of Surgery in Erasto Gaertner Hospital, from
      January 1987 to January 1998, divided according to realization of neoadjuvant
      treatment or not. Variables related to patient (sex, age, general condition,
      ponderal loss, co-morbidities, tabagism), to tumor (histological type,
      localization, staging) and to surgical procedure (type and localization of
      anastomosis, surgical time, hospitalization time) were noted and related to
      postoperative complications and mortality. RESULTS: Ninety-nine patients (71.2%)
      were of male sex. The predominant histological type was squamous cell carcinoma
      in 94.7% of the cases. Eighty-eight patients (66.6%) were smokers, and the main
      co-morbidities noted were: chronic obstructive pulmonary disease (29.55%) and
      arterial hypertension (15.15%). The main localization of the tumor was inferior
      thoracic segment (56.06%), with average tumoral extension of 47,72 (8-70) mm. Six
      patients (4.54%) were stage I, 44 (33.33%) IIA, 24 (18.18%) IIB, 38 (28.80%) III
      and 17 (12.90%) IV. Considering the neoadjuvant treatment, 39 patients (29.54%)
      were submitted to chemotherapy and 22 (16.67%) to radiotherapy. The postoperative
      complications were 74.35% (p=0.0002) and 72.73% (p=0.0037), respectively. The
      complication rate was 39.3% and hospital lethality 13.70%, represented more
      frequently by pleuropulmonar causes. CONCLUSION: Neoadjuvant chemotherapic and
      radiotherapeutic treatments were related to superior occurrence of postoperative
      complications, without influence on hospital lethality.

PMID- 14666357
TI  - [Influence of body fat distribution on the prevalence of arterial hypertension
      and other cardiovascular risk factors in obese patients].
AB  - INTRODUCTION: Obese people are at higher cardiovascular risk than people with
      normal body weight. The objective of this study was to establish the relationship
      between obesity, body fat distribution and cardiovascular risk factors. METHODS:
      Body mass index (BMI), waist-hip ratio (WHR) systolic (SBP) and diastolic blood
      pressure (DBP), plasma cholesterol, triglycerides and glucose levels were
      determined in a population of 499 overweight and obese patients (432F/67M; age 39
      12.9y). RESULTS: High prevalence of abnormal glucose tolerance or diabetes
      (21.8%), hypercholesterolenemia (49.1%), hypertri glyceridemia (21.3%) and
      hypertension (43.8%) were found in this population. The prevalence of
      hypertension increased from 23% in patients with BMI 25-29.9 kg/m  to 67.1%
      (p<0.05) in those with BMI > 40kg/m  and also from 35.7% in patients with WHR
      between 0.73 and 0.88 to 66.6% in those with WHR >0.97 (p<0.05). In addition, a
      correlation was found between the waist circumference and SBP (r=0.35; p<0.0001).
      In the hypertensive group, but not in the normotensive, SBP increased with BMI,
      from 150 12 mmHg in the overweight group to 161 18mmHg in that with BMI > 40kg/m
      , (p<0.05). CONCLUSION: Our data reinforce the association between obesity and
      high cardiovascular risk. In addition, our findings suggested a role for body fat
      distribution in the development of hypertension in obese patients.

PMID- 14666358
TI  - [Knowledge on screening and diagnosis of breast cancer among gynecologists in
      Goias State (Brazil)].
AB  - OBJECTIVES: To evaluate the knowledge level on the screening and diagnosis of
      breast cancer among the gynecologists of the State of Goias, Brazil. METHODS:
      Questionnaires containing professional information and questions on breast cancer
      screening were posted for all the 427 gynecologists associated to the Goias
      Society of Gynecology and Obstetrics, between May and July of 1999. RESULTS: Of
      the 427 questionnaires, 26 (6%) were returned because incorrect mailing address.
      Of the 401 doctors who received the questionnaire, 85 (21%) answered and returned
      them back. Of these, 28% were female; the average of the profession time was of
      17 years. The medical residence was the highest title level for 70%. The average
      age of the doctors was 44 years. The rates of correct answers were: 94% for the
      knowledge of the most frequent sign of breast cancer, 75% for the best method for
      screening, 88% for the period of when the mammography begins, 93% for the
      periodicity of the mammography after the 50 years and 83% about the indication of
      the complementary ultrasound. The doctors who have studied in a program of
      medical residence was the only factor that influenced the rate of correct
      answers, if compared to those that did not cursed it. The professional's gender,
      the Title in Gynecology and Obstetrics Specialty (TEGO) holders and the city of
      work did not influence the rates of correct answers. CONCLUSION: The
      gynecologists of the State of Goias who answered the questionnaire have a good
      knowledge on the screening and diagnosis of breast cancer. Medical residence was
      the single factor that influenced the rate of correct answers.

PMID- 14666359
TI  - [Dopamine and kidney in sepsis: a systematic review].
AB  - Acute renal failure has a high morbidity and mortality in critically ill
      patients. Severe sepsis and septic shock are important risk factors for the
      development of acute renal failure. Low-dose dopamine (0.5 to 3 mg/kg/min) has
      been used for decades as a renal-protective therapy in such patients, even in the
      absence of any controlled study to support this concept. BACKGROUND: To Check the
      literature for evidences supporting the routine use of low-dose dopamine in
      severe sepsis and septic shock. METHODS: Systematic review of the literature, on
      electronic databasis (MEDLINE, EMBASE and LILACS), and handsearching. RESULTS:
      Only five randomized clinical trials were found, but none of them studied renal
      outcomes. Eight cases series studies were included on a qualitative review.
      Dopamine was associated with some adverse effects, such as increase in pulmonary
      shunting, tachyarrhythmias, and increase in pulmonary artery pressure, that were
      not statistically significant. Mortality also did not change with the use of
      dopamine. CONCLUSIONS: There are no sufficient evidences in the literature to
      support the routine use of low-dose dopamine as a renal protective agent in
      severe sepsis and septic shock.

PMID- 14666360
TI  - [The role of distance education in continuing medical education: a critical
      review].
AB  - This paper reviews findings of recent literature which have systematically
      evaluated outcomes of continuing medical education programs worldwide, methods
      for measuring especific demands in medical areas, and quality and reliability of
      contents related to such programs. Particular features of the Brazilian health
      context and internet technologies are described, as well as possible directions
      towards life-long medical education development in Brazil for the next few years.

PMID- 14666361
TI  - [Management of gestational diabetes].
AB  - The authors go review recent advanes in the treatment of gestational diabetes,
      giving emphasis to the peculiarities of this both clinical and obstetric disease.
      The covered topics covered include diet, exercise, metabolic control, insulin
      therapy and new therapeutic approaches, such as the use of oral hipoglycaemic
      agents.

PMID- 14666362
TI  - [Medication errors: who is responsible?].
AB  - New diagnostic and therapeutic technologies are used with growing frequency,
      improving the quality of medical assistance and increasing life expectancy.
      Health care, however, is becoming progressively more expensive and complex.
      Adverse events related to medical assistance, particularly errors, are becoming
      public, being debated and judged in courts. Given their training, health workers
      are not prepared to deal with errors, which are associated with shame, fear and
      punishment. The approach to errors in the health system is usually
      individualistic, considering such events as acts of insecurity performed by
      careless, non-motivated and ill-trained persons. The tendency is to hide errors
      when they occur, with the result that an important learning opportunity is lost.
      There is another way to deal with errors, a systemic view that has obtained
      positive results in sectors such as aviation, anesthesiology and unit-dose drug
      distribution systems. These systems have varied degrees of safety and should take
      into account human limitations when designed and applied. A change in paradigm is
      needed when dealing with drugs, as it is not enough for a drug to have quality
      assurance, but the complete process of drug use should be safe. Medication
      errors, avoidable by definition, are at present a serious public health issue,
      leading to loss of lives and significant financial losses. A systemic approach to
      medication errors may disclose failures in the process as a whole, and
      improvements can be implemented to reduce their occurrence.

PMID- 14666363
TI  - [Pulmonary embolic ischemia: clinical and experimental aspects].
AB  - Pulmonary ischemia is usually related with embolics mechanisms, and this mechanic
      artery occlusion is not always followed by severe ischemic consequences, because
      the bronchial circulation changes supply the areas without blood flow. However,
      small artery vascular remodeling occurs, related to persistent high pulmonary
      pressure levels, mainly in the chronic pulmonary thromboembolism. Experimental
      models have been produced to study the relation-ship between mechanic artery
      occlusion, pulmonary hypertension and vascular remodeling, however, more
      systematic evaluation is necessary to understand such a these relation-ship, in
      the ischemic and not ischemic lung parenchyma.

PMID- 14666365
TI  - To: Walter U, Toepfer T, Dittmar KE et al. (2003) Pancreatic NOD beta cells
      express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta
      cells strongly increases during progression to autoimmune diabetes. Diabetologia
      46:1106-1114.

PMID- 14666364
TI  - Beta-cell dysfunction and glucose intolerance: results from the San Antonio
      metabolism (SAM) study.
AB  - AIMS/HYPOTHESIS: Both insulin resistance and beta-cell dysfunction play a role in
      the transition from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM)
      through impaired glucose tolerance (IGT). The aim of the study was to define the
      level of glycaemia at which beta-cell dysfunction becomes evident in the context
      of existing insulin resistance. METHODS: Insulin response (OGTT) and insulin
      sensitivity (euglycaemic insulin clamp) were evaluated in 388 subjects in the San
      Antonio Metabolism (SAM) study (138 NGT, 49 IGT and 201 T2DM). In all subjects
      the insulin secretion/insulin resistance index (DeltaI/DeltaG/IR) was calculated
      as the ratio of the increment in plasma insulin to the increment in plasma
      glucose during the OGTT divided by insulin resistance, as measured during the
      clamp. RESULTS: In lean NGTs with a 2-h plasma glucose concentration (2-h PG)
      between 5.6 and 6.6 and between 6.7 and 7.7 mmol/l, there was a progressive
      decline in DeltaI/DeltaG/IR compared with NGTs with a 2-h PG less than 5.6
      mmol/l. There was a further decline in DeltaI/DeltaG/IR in IGTs with a 2-h PG
      between 7.8 and 9.3 and between 9.4 and 11.0 mmol/l, and in Type 2 diabetic
      patients with a 2-h PG greater than 11.1 mmol/l. Lean and obese subjects showed
      coincident patterns of relation of 2-h PG to DeltaI/DeltaG/IR.
      CONCLUSION/INTERPRETATION: When the plasma insulin response to oral glucose is
      related to the glycaemic stimulus and severity of insulin resistance, there is a
      progressive decline in beta-cell function that begins in "normal" glucose
      tolerant individuals.

PMID- 14666366
TI  - Plasminogen kringle 5 reduces vascular leakage in the retina in rat models of
      oxygen-induced retinopathy and diabetes.
AB  - AIMS/HYPOTHESIS: Retinal vascular leakage is an early pathological feature in
      diabetic retinopathy and can lead to macular oedema and loss of vision.
      Previously we have shown that plasminogen kringle 5 (K5), an angiogenic
      inhibitor, inhibits retinal neovascularisation in the rat model of oxygen-induced
      retinopathy (OIR). The purpose of this study was to examine the effect of K5 on
      vascular leakage in the retina. METHODS: Neonatal rats were exposed to hyperoxia
      to induce OIR. Diabetes was induced in adult rats by injecting streptozotocin.
      Vascular permeability was measured by Evans blue method. Expression of vascular
      endothelial growth factor (VEGF) was evaluated using immunohistochemistry and
      western blot analysis. RESULTS: Rats with OIR and diabetes showed abnormal
      vascular hyperpermeability in the retina and iris. Intravitreal injection of K5,
      reduced vascular permeability in both animal models, but did not affect
      permeability in normal rats. K5 reduced vascular permeability at doses
      substantially lower than that required for inhibition of retinal
      neovascularisation. The K5-induced reduction in vascular permeability correlated
      with its down-regulation of VEGF expression in the retina. Moreover, K5 inhibited
      IGF-1-induced hyperpermeability, which is known to arise through up-regulation of
      endogenous VEGF expression. However, K5 had no effect on the hyperpermeability
      induced by injection of exogenous VEGF. CONCLUSIONS/INTERPRETATION: Very low
      doses of K5 reduce pathological vascular leakage in the retina. K5 thus has
      therapeutic potential in the treatment of diabetic macular oedema. This effect
      can be ascribed, at least in part, to the down-regulation of endogenous VEGF
      expression.

PMID- 14666367
TI  - Combined gastrin and epidermal growth factor treatment induces islet regeneration
      and restores normoglycaemia in C57Bl6/J mice treated with alloxan.
AB  - AIMS/HYPOTHESIS: Increasing beta-cell mass and/or function could restore glucose
      homeostasis in diabetes mellitus. Hitherto, trophic factors for beta-cell
      regeneration after toxic events have been difficult to identify. We evaluated the
      application of gastrin and epidermal growth factor after alloxan-induced
      pancreatic beta-cell damage. METHODS: After alloxan treatment (70 mg/kg), mice
      were implanted with Alzet osmotic minipumps releasing gastrin and epidermal
      growth factor for one week. We monitored glycaemia, did histological analyses of
      the pancreata and quantified pancreatic beta-cell mass and insulin content.
      RESULTS: Alloxan treatment alone resulted in a persisting hyperglycaemic state.
      Combined gastrin and epidermal growth factor treatment restored normoglycaemia in
      3 days, an effect which seemed permanent. Glucose tolerance tests showed normal
      glucose responsiveness. Gastrin on its own and epidermal growth factor on its own
      did not alleviate hyperglycaemia. Islet mass, islet density and pancreatic
      insulin content were higher in mice treated with gastrin and epidermal growth
      factor than in untreated mice with persisting hyperglycaemia. In normoglycaemic
      control mice treatment with gastrin and epidermal growth factor did not affect
      these parameters. We detected transitional cytokeratin-positive ductal to
      endocrine insulin-expressing cells and noted increased ductal but not beta-cell
      proliferation. CONCLUSIONS/INTERPRETATION: Our results show that combined
      treatment with gastrin and epidermal growth factor can induce sufficient
      regeneration of a functional islet mass to restore glucose homeostasis.

PMID- 14666368
TI  - Variation in the FABP2 promoter affects gene expression: implications for prior
      association studies.
AB  - AIMS/HYPOTHESIS: An Ala54Thr polymorphism in the FABP2 gene has previously been
      associated with insulin resistance and lipid oxidation rates in Pima Indians.
      Ala54Thr functionally alters the protein's ability to bind and transport dietary
      fatty acids. In the current report, we sought additional functional variation in
      FABP2 by sequencing putative regulatory regions. METHODS: More than 1.2 Kb of the
      putative promoter of FABP2 was sequenced in 20 Pima subjects. Variations were
      genotyped in 84 additional Pima Indian subjects to assess haplotype combinations.
      Functional activities of variant and nonvariant promoters were compared in Caco-2
      cells transfected with luciferase reporter constructs. RESULTS: Seven variations
      were identified in the FABP2 promoter in Pima Indians. Genotypes of these
      variants were in complete concordance with each other, and were in complete
      concordance with Ala54Thr. Therefore, only two promoter alleles were observed in
      Pima Indians, an Ala54-associated promoter and a Thr54-associated promoter. In
      contrast, genotyping of these variants in Caucasian DNA showed multiple genotypic
      combinations. In vitro reporter assays indicated that the Thr54-associated
      promoter in Pima Indians resulted in a threefold reduction in promoter activity
      as compared to Ala54-associated promoter. CONCLUSION/INTERPRETATION: Two
      functional variations exist in FABP2--the coding Ala54Thr and the variant
      promoter. In the Pima Indian population, but not the Caucasian population, these
      two functional variants are always carried on the same allele. Therefore, some of
      the in vivo phenotypic associations previously attributed to the Ala54Thr
      substitution, which alters binding characteristics of the protein, could instead
      be due to promoter variation, which alters expression levels.

PMID- 14666369
TI  - Neutrophil antigen exposure is altered with age in relatives of patients with
      Type 2 diabetes.

PMID- 14666370
TI  - Braking the accelerator hypothesis?

PMID- 14666371
TI  - Cucumis monosomic alien addition lines: morphological, cytological, and genotypic
      analyses.
AB  - Cucumis hystrix Chakr. (HH, 2n=24), a wild relative of the cultivated cucumber,
      possesses several potentially valuable disease-resistance and abiotic stress
      tolerance traits for cucumber ( C. sativus L., CC, 2n=14) improvement. Numerous
      attempts have been made to transfer desirable traits since the successful
      interspecific hybridization between C. hystrix and C. sativus, one of which
      resulted in the production of an allotriploid (HCC, 2n=26: one genome of C.
      hystrix and two of C. sativus). When this genotype was treated with colchicine to
      induce polyploidy, two monosomic alien addition lines (MAALs) (plant nos. 87 and
      517: 14 CC+1 H, 2n=15) were recovered among 252 viable plants. Each of these
      plants was morphologically distinct from allotriploids and cultivated cucumbers.
      Cytogenetic and molecular marker analyses were performed to confirm the genetic
      constitution and further characterize these two MAALs. Chromosome counts made
      from at least 30 meristematic cells from each plant confirmed 15 nuclear
      chromosomes. In pollen mother cells of plant nos. 87 and 517, seven bivalents and
      one univalent were observed at diakinesis and metaphase I; the frequency of
      trivalent formation was low (about 4-5%). At anaphase I and II, stochastic and
      asymmetric division led to the formation of two gamete classes: n=7 and n=8;
      however, pollen fertility was relatively high. Pollen stainability in plant no.
      87 was 86.7% and in plant no. 517 was 93.2%. Random amplified polymorphic DNA
      analysis was performed using 100 random 10-base primers. Genotypes obtained with
      eight primers (A-9, A-11, AH-13, AI-19, AJ-18, AJ-20, E-19, and N-20) showed a
      band common to the two MAAL plants and C. hystrix that was absent in C. sativus,
      confirming that the alien chromosomes present in the MAALs were derived from C.
      hystrix. Morphological differences and differences in banding patterns were also
      observed between plant nos. 87 and 517 after amplification with primers AI-5, AJ
      13, N-12, and N-20, suggesting that these plants may contain different C. hystrix
      chromosomes.

PMID- 14666373
TI  - Cotton ball-vacuum compression for dressing small wounds.

PMID- 14666372
TI  - Reliability of a standardized reading chart system: variance component analysis,
      test-retest and inter-chart reliability.
AB  - BACKGROUND: The purpose of this study was to analyze statistically the test
      retest and inter-chart reliability of three standardized Radner Reading Charts
      with respect to reading acuity, maximum reading speed, critical print size and
      LogRAD/LogMAR ratio and to quantitatively identify the sources of variability.
      METHODS: At two testing sessions (3 to 4 weeks apart), 36 volunteers read
      monocularly all three Radner Reading Charts in randomized order (orthogonal Latin
      square design). The subjects were grouped according to their distance LogMAR
      visual acuity (group 1, 0.1 or better; group 2, 0.12-0.4; group 3, 0.42-0.8).
      Based on these 216 reading tests, crude correlations were calculated between the
      two testing sessions and between the three charts, and "variance component
      analyses" were performed for all variables. RESULTS: For all visual acuity groups
      and variables, the test-retest and the inter-chart reliability was high. The
      variance component analyses showed that the differences between individuals
      predominantly influenced the variance, whereas the effect of the test replication
      was low. The three charts caused minimal variability, indicating equality for
      clinical examinations. CONCLUSION: The standardized Radner Reading Charts provide
      clinically reliable and reproducible results for individuals with normal eyesight
      and for patients with visual impairment. These findings indicate that reading
      test systems, which consider the current international standards for visual
      acuity measurements (EN ISO 8596, NAS-NRC) and the psychophysical requirements
      for controlling optical item interactions, can provide reliable measures for
      clinical and scientific analyses of reading performance.

PMID- 14666374
TI  - Accommodation behaviour during prey capture in the Vietnamese leaf turtle (
      Geoemyda spengleri).
AB  - Vietnamese leaf turtles ( Geoemyda spengleri) were tested for their ability to
      focus on prey objects at various distances. Accommodation was continuously
      measured by infrared photoretinoscopy. All animals investigated during this study
      showed a surprisingly high precision of accommodation over a range of over 30 D.
      Measured accommodation matched the target distance accurately for distances
      between 3 and 17 cm. The turtles switched between independent and coupled
      accommodation in the two eyes. Independent accommodation was observed when the
      turtles inspected their environment visually without a defined object of
      interest. Coupled accommodation was only observed during binocular prey fixation.
      When a turtle aimed at a target, the symmetrical focus of both eyes persisted
      even if vision was totally blocked in one eye or altered by ophthalmic lenses.
      This suggests that the eyes were linked by internal neuronal mechanisms. The
      pupil of the eye responded clearly to changes in ambient light intensity. A
      strong decrease in pupil size was also observed when the eye was focused on a
      close target. In this case, the constriction of the pupil probably aids in the
      deformation of the eye lens during near-accommodation.

PMID- 14666375
TI  - Variations in the off-axis refractive state in the eye of the Vietnamese leaf
      turtle (Geoemyda spengleri).
AB  - Lower-field myopia has been described for various vertebrates as an adaptation
      that permits the animal to keep the ground in focus during foraging, and, at the
      same time, to look out for distant objects, such as predators, in the upper
      visual field. Off-axis measurements with infrared photoretinoscopy in the eye of
      Geoemyda spengleri revealed a constant refractive state in the horizontal plane
      of the visual field but variable refraction in the vertical plane. In the three
      turtles investigated, the refractions increased continuously from the ventral to
      the dorsal visual field over a range of 35, 40 and 56 D, respectively. While this
      finding confirms the presence of an adaptive change of the refractive state
      equivalent to lower field myopia, subsequent measurements with a rotated
      retinoscope showed that at least part of the variation in the ventral field was
      attributed to astigmatism. The reason for this astigmatism is unknown. Anatomical
      investigation of the retina revealed that the constant refractive values in the
      horizontal plane corresponded to a stripe of increased ganglion cell density. A
      maximum density of 4,200 ganglion cells mm(-2) was counted in the centre of this
      visual streak.

PMID- 14666376
TI  - 3D CT modeling of hepatic vessel architecture and volume calculation in living
      donated liver transplantation.
AB  - The aim of this study was to evaluate a software tool for non-invasive
      preoperative volumetric assessment of potential donors in living donated liver
      transplantation (LDLT). Biphasic helical CT was performed in 56 potential donors.
      Data sets were post-processed using a non-commercial software tool for
      segmentation, volumetric analysis and visualisation of liver segments. Semi
      automatic definition of liver margins allowed the segmentation of parenchyma.
      Hepatic vessels were delineated using a region-growing algorithm with
      automatically determined thresholds. Volumes and shapes of liver segments were
      calculated automatically based on individual portal-venous branches. Results were
      visualised three-dimensionally and statistically compared with conventional
      volumetry and the intraoperative findings in 27 transplanted cases. Image
      processing was easy to perform within 23 min. Of the 56 potential donors, 27 were
      excluded from LDLT because of inappropriate liver parenchyma or vascular
      architecture. Two recipients were not transplanted due to poor clinical
      conditions. In the 27 transplanted cases, preoperatively visualised vessels were
      confirmed, and only one undetected accessory hepatic vein was revealed.
      Calculated graft volumes were 1110 +/- 180 ml for right lobes, 820 ml for the
      left lobe and 270 +/- 30 ml for segments II+III. The calculated volumes and
      intraoperatively measured graft volumes correlated significantly. No significant
      differences between the presented automatic volumetry and the conventional
      volumetry were observed. A novel image processing technique was evaluated which
      allows a semi-automatic volume calculation and 3D visualisation of the different
      liver segments.

PMID- 14666377
TI  - Primary lung cancer: treatment with radio-frequency thermal ablation.
AB  - Primary lung cancer is the most frequently diagnosed malignancy in the world and
      the leading cause of death from cancer [1]. When the initial diagnosis is made,
      most cases are inoperable or the patients' condition does not permit surgical
      interventions [2]. For patients with inoperable lung cancer, percutaneous radio
      frequency thermal ablation (RFA) under CT guidance represents an alternative and
      minimally invasive treatment. It can also be applied in combination with
      radiation therapy and chemotherapy. We report three cases treated by percutaneous
      CT-guided RF ablation, from which two had post-operative recurrent tumor and one
      was inoperable.

PMID- 14666378
TI  - Reactivation of Epstein-Barr virus in patients with systemic lupus erythematosus.
AB  - A link between Epstein-Barr Virus (EBV) and systemic lupus erythematosus (SLE)
      has been suggested. However, recent advances in molecular technology now permit
      more detailed analysis. Sera from SLE patients were tested for antibodies to
      several EBV antigens and had a significantly higher prevalence of immunoglobulin
      G antibodies against EBV early antigens than in normal or disease controls. This
      suggests that recent EBV infection or virus reactivation was occurring in these
      patients.

PMID- 14666379
TI  - Characterization of tetrandrine, a potent inhibitor of P-glycoprotein-mediated
      multidrug resistance.
AB  - Multidrug resistance (MDR) is one of the main obstacles in tumor chemotherapy. A
      promising approach to solving this problem is to utilize a nontoxic and potent
      modulator able to reverse MDR, which in combination with anticancer drugs
      increases the anticancer effect. Experiments were carried out to examine the
      potential of tetrandrine (Tet) as a MDR-reversing agent. Survival of cells
      incubated with Tet at 2.5 micromol/l for 72 h was over 90%. Tet at 2.5 micromol/l
      almost completely reversed resistance to vincristine (VCR) in KBv200 cells. Tet
      at a concentration as low as 0.625 micromol/l produced a 7.6-fold reversal of
      MDR, but showed no effect on the sensitivity of drug-sensitive KB cells in vitro.
      In the KBv200 cell xenograft model in nude mice, neither Tet nor VCR inhibited
      tumor growth. However, VCR and Tet combined inhibited tumor growth by 45.7%,
      61.2% and 55.7% in three independent experimental settings. In the KB cell
      xenograft model in nude mice, Tet did not inhibit tumor growth, but VCR and the
      combination of VCR and Tet inhibited tumor growth by 40.6% and 41.6%,
      respectively. Mechanism studies showed that Tet inhibited [(3)H]azidopine
      photoaffinity labeling of P-gp and increased accumulation of VCR in MDR KBv200
      cells in a concentration-dependent manner. The results suggest that Tet is a
      potent MDR-reversing agent in vitro and in vivo. Its mechanism of action is via
      directly binding to P-gp and increasing intracellular VCR accumulation.

PMID- 14666380
TI  - Rapid improvement of disseminated aspergillosis with caspofungin/voriconazole
      combination in an adult leukemic patient.
AB  - A 57-year-old man with acute myeloid leukemia (AML) French-American-British (FAB)
      4 developed disseminated invasive cerebral and pulmonary aspergillosis during
      postinduction aplasia. According to international consensus, infection was
      categorized as probable (two host factors: deep neutropenia for >10 days and
      refractory fever for >96 h; major clinical criteria of lower respiratory tract
      and CNS invasive fungal infection; positive results for galactomannan antigen in
      three blood samples). After the failure of standard amphotericin-based therapy,
      the spectacular regression of multifocal brain and lung lesions was rapidly
      achieved under a caspofungin acetate/voriconazole combination. Further permanent
      caspofungin maintenance with voriconazole added during aplasia periods permitted
      two consolidation courses and autograft-based intensification without any delay.

PMID- 14666382
TI  - Vascular endothelial growth factor inhibits maturation of dendritic cells induced
      by lipopolysaccharide, but not by proinflammatory cytokines.
AB  - PURPOSE: Dendritic cells (DCs) play an important role in the host's
      immunosurveillance against cancer. It has been shown that the function of DCs is
      impaired and their population decreased in a cancer-bearing host. In the present
      study, we investigated the mechanism of down-regulation of DCs in a cancer
      bearing host. METHODS: We evaluated the relationship between DC infiltration and
      production of vascular endothelial growth factor (VEGF) in carcinoma tissue by
      immunohistochemistry. Furthermore, functional and phenotypical alterations of DCs
      were evaluated when monocyte-derived, mature DCs were treated with VEGF in vitro.
      Monocyte-derived DCs were generated in a culture of monocyte with interleukin 4
      (IL-4) and granulocyte-macrophage colony-stimulating factor, and the maturation
      of DCs was induced by either lipopolysaccharide (LPS) or a proinflammatory
      cytokine cocktail: tumor-necrosis factor alpha, prostaglandin E2, IL-6, and IL
      1beta. RESULTS: A significant inverse correlation was found between the density
      of DCs and the quantity of VEGF production in gastric carcinoma tissue (r=-0.39,
      p<0.05). In LPS-induced maturation, the ability of mature DCs to stimulate
      allogenic T cells and produce IL-12 (p70 heterodimer) was suppressed by the
      addition of VEGF in a dose-dependent manner. A lesser expression of costimulatory
      molecules (CD80 and CD86) was seen in DCs treated with exogenous VEGF than in DCs
      not treated with VEGF. The population of dead DCs (early and late apoptosis)
      treated with VEGF increased more than that without VEGF treatment, using the
      annexin V and propidium iodide evaluation in DCs matured by LPS. In contrast, in
      DCs matured by the proinflammatory cytokine cocktail, the down-regulation of
      costimulatory molecules and induction of DC apoptosis was not seen. CONCLUSIONS:
      These findings show that the inhibition of DC maturation by VEGF differs
      depending on the maturation status of the DCs.

PMID- 14666383
TI  - Challenging cases in thyroid cancer: a multidisciplinary approach.
AB  - Recurrent thyroid cancer can present many complex management problems.
      Unfortunately, recurrent thyroid cancer is often refractory to radioiodine
      therapy. The proper use of external beam irradiation and surgical interventions
      can provide regional control of localized recurrences. Because of the complex
      nature of these patients, a multidisciplinary team approach to management which
      includes specialists in thyroid medicine and surgery, head and neck radiotherapy,
      and nuclear medicine often is required to provide individualized, optimal
      multimodality treatment recommendations. In this article we review a
      multidisciplinary team approach to a patient with widespread, radioiodine
      refractory bone metastases from follicular thyroid cancer and to a patient with
      unresectable central neck recurrence of papillary thyroid cancer.

PMID- 14666384
TI  - 18F-labelled annexin V: a PET tracer for apoptosis imaging.
AB  - Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on
      its ability to identify extracellular phosphatidylserine, which arises during
      apoptosis. In the present study, we examined the synthesis of fluorine-18
      labelled annexin V as a positron emission tomography tracer for apoptosis
      imaging. The distribution of [18F]annexin V and technetium-99m labelled annexin
      V, a well-characterised SPET tracer for apoptosis imaging, was compared.
      [18F]annexin V was synthesised using N-succinimidyl 4-[18F]fluorobenzoate as an
      18F labelling reagent. Synthesised and purified [18F]annexin V was confirmed by
      SDS-PAGE. In an ex vivo imaging experiment, [18F]annexin V was intravenously
      injected into rats 24 h after the induction of myocardial ischaemia, and
      accumulation in the left ventricle was examined. [18F]annexin V accumulated in
      the infarct area of the left ventricle, where apoptotic cells were observed. In
      separate experiments, [18F]annexin V or [(99m)Tc]annexin V was intravenously
      injected into ischaemic or normal animals, and the distribution of the tracers
      was compared. In ischaemic animals, accumulation of [18F]annexin V and
      [(99m)Tc]annexin V in the infarct area was about threefold higher than in the non
      infarct area. Furthermore, the ratio of accumulation in the normal heart to the
      blood radioactivity was not significantly different between the tracers. In
      normal animals, however, the uptake of [18F]annexin V in the liver, spleen and
      kidney was much lower than that of [(99m)Tc]annexin V. The low uptake of
      [18F]annexin V in these organs might represent an advantage over [(99m)Tc]annexin
      V.

PMID- 14666386
TI  - Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines.
AB  - We have previously shown a correlation between the absence of technetium-99m
      methoxyisobutylisonitrile ((99m)Tc-MIBI) uptake and overexpression of the anti
      apoptotic protein Bcl-2 in human breast carcinoma. To establish a direct cause
      effect relationship between Bcl-2 overexpression and reduced (99m)Tc-MIBI uptake,
      MCF-7 and T47D breast cancer cell lines were stably transfected with the human
      Bcl-2 gene to increase intracellular protein levels and tested for (99m)Tc-MIBI
      uptake. All clones overexpressing Bcl-2 showed a dramatic reduction of (99m)Tc
      MIBI uptake as compared with mock transfected control cells. Tracer uptake was
      promptly and partially restored by induction of apoptosis with staurosporine
      treatment. After 4.5 h of staurosporine treatment, a tenfold increase in (99m)Tc
      MIBI uptake was observed in treated as compared with untreated Bcl-2
      overexpressing cells. Our findings provide a rational basis for the development
      of an in vivo test to detect Bcl-2 overexpression in human tumours.

PMID- 14666387
TI  - Comparison of whole-body 18F-FDG PET, 99mTc-MIBI SPET, and post-therapeutic 131I
      Na scintigraphy in the detection of metastatic thyroid cancer.
AB  - The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission
      tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by
      many investigators, but in only a small number of studies have FDG-PET images
      been compared with those obtained using other non-iodine tumour-seeking
      radiopharmaceuticals. In most of the studies, planar imaging was performed for
      comparison using thallium-201 chloride or technetium-99m 2
      methoxyisobutylisonitrile ((99m)Tc-MIBI). Furthermore, FDG-PET studies were not
      always performed in the hypothyroid state with increased levels of thyroid
      stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim
      of this study was to compare the ability of FDG-PET to detect metastatic DTC with
      that of (99m)Tc-MIBI whole-body single-photon emission tomography (SPET) and post
      therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen
      patients (8 men, 11 women; age range, 38-72 years, mean 60 years; 17
      thyroidectomised and 2 inoperable patients following (131)I ablation of the
      remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with
      metastatic DTC underwent FDG-PET whole-body scan (WBS) and (99m)Tc-MIBI SPET WBS
      at an interval of less than 1 week, followed by (131)I therapy. The SPET images
      were reconstructed using the maximum likelihood expectation maximisation (ML-EM)
      method. All patients were hypothyroid at the time of each scan. (131)I WBS was
      performed 3-5 days after oral administration of the therapeutic dose. A total of
      32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as
      metastases, as confirmed by histopathology and/or other imaging modalities (X
      ray, US, CT, MRI, bone, (201)Tl and (131)I scans). FDG-PET, (99m)Tc-MIBI SPET and
      post-therapeutic (131)I scintigraphy respectively revealed a total of 26 (81.3%),
      20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated
      nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%),
      seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the
      six bone metastases (83.3%). FDG-PET and (99m)Tc-MIBI SPET were positive in 17
      (78.3%) and 14 (63.6%) of the 22 (131)I-positive lesions, respectively, and also
      in nine (90.0%) and six (60.0%) of the ten (131)I-negative lesions, respectively.
      Three of the five (131)I-positive and FDG-PET-negative lesions were miliary type
      lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of
      FDG-PET with (99m)Tc-MIBI SPET revealed concordant results in 24 lesions, and
      discordant results in eight lesions (seven with positive FDG-PET alone and one
      with positive (99m)Tc-MIBI SPET alone). IN CONCLUSION: (a) even using whole-body
      SPET, FDG PET is superior to (99m)Tc-MIBI in terms of ability to detect
      metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the
      previous studies could partly be due to increased serum TSH.

PMID- 14666388
TI  - Mesophilic and thermophilic BTEX substrate interactions for a toluene
      acclimatized biofilter.
AB  - Benzene, toluene, ethylbenzene and xylene (BTEX) substrate interactions for a
      mesophilic (25 degrees C) and thermophilic (50 degrees C) toluene-acclimatized
      composted pine bark biofilter were investigated. Toluene, benzene, ethylbenzene,
      o-xylene, m-xylene and p-xylene removal efficiencies, both individually and in
      paired mixtures with toluene (1:1 ratio), were determined at a total loading rate
      of 18.1 g m(-3) h(-1) and retention time ranges of 0.5-3.0 min and 0.6-3.8 min
      for mesophilic and thermophilic biofilters, respectively. Overall, toluene
      degradation rates under mesophilic conditions were superior to degradation rates
      of individual BEX compounds. With the exception of p-xylene, higher removal
      efficiencies were achieved for individual BEX compounds compared to toluene under
      thermophilic conditions. Overall BEX compound degradation under mesophilic
      conditions was ranked as ethylbenzene >benzene > o-xylene > m-xylene > p-xylene.
      Under thermophilic conditions overall BEX compound degradation was ranked as
      benzene > o-xylene >ethylbenzene > m-xylene > p-xylene. With the exception of o
      xylene, the presence of toluene in paired mixtures with BEX compounds resulted in
      enhanced removal efficiencies of BEX compounds, under both mesophilic and
      thermophilic conditions. A substrate interaction index was calculated to compare
      removal efficiencies at a retention time of 0.8 min (50 s). A reduction in
      toluene removal efficiencies (negative interaction) in the presence of individual
      BEX compounds was observed under mesophilic conditions, while enhanced toluene
      removal efficiency was achieved in the presence of other BEX compounds, with the
      exception of p-xylene under thermophilic conditions.

PMID- 14666389
TI  - Characterisation of nitrilase and nitrile hydratase biocatalytic systems.
AB  - Biocatalytic transformations converting aromatic and arylaliphatic nitriles into
      the analogous related amide or acid were investigated. These studies included
      synthesis of the beta-substituted nitrile 3-hydroxy-3-phenylpropionitrile,
      subsequent enrichment and isolation on this substrate of nitrile-degrading
      microorganisms from the environment, and a comparative study of enzymatic
      reactions of nitriles by resting cell cultures and enzymes. Each biocatalyst
      exhibited a distinctive substrate selectivity profile, generally related to the
      length of the aliphatic chain of the arylaliphatic nitrile and the position of
      substituents on the aromatic ring or aliphatic chain. Cell-free nitrilases
      generally exhibited a narrower substrate range than resting whole cells of
      Rhodococcus strains. The Rhodococcus strains all exhibited nitrile hydratase
      activity and converted beta-hydroxy nitriles (but did not demonstrate
      enantioselectivity on this substrate). The biocatalysts also mediated the
      synthesis of a range of alpha-hydroxy carboxylic acids or amides from aldehydes
      in the presence of cyanide. The use of an amidase inhibitor permits halting the
      nitrile hydratase/amidase reaction at the amide intermediate.

PMID- 14666390
TI  - Behaviour of dehydrated baker's yeast during reduction reactions in a biphasic
      medium.
AB  - The behaviour of dry baker's yeast ( Saccharomyces cerevisiae type II, Sigma)
      used as biocatalyst without preliminary growth for the synthesis of 2-heptanol
      from 2-heptanone in a biphasic system is presented. Cells undergo intracellular
      trehalose consumption with a stoichiometric ethanol production during the first
      15 h of the process. This metabolism is then replaced by acetate accumulation.
      These reactions are disconnected from the biocatalytic reaction and do not
      provide reduced cofactors. 2-Heptanone is metabolised by two pathways. The first
      leads to 2-heptanol (molar yield close to 55%, enantioselectivity higher than
      99%, with a slight decrease at the end of the process) and the second corresponds
      to material incorporation into the biomass. This latter phenomenon is assumed to
      provide the biocatalyst with the reduced cofactors needed for the reduction
      process. Overall, the process yielded ca. 1.4 g/l 2-heptanol in 50 h reaction,
      which is close to that observed with fresh cells previously grown for 15 h.

PMID- 14666391
TI  - Characterisation of cellobiose dehydrogenases from the white-rot fungi Trametes
      pubescens and Trametes villosa.
AB  - Cellobiose dehydrogenase (CDH) is an extracellular haemoflavoenzyme that is
      produced by a number of wood-degrading and phytopathogenic fungi and it has a
      proposed role in the early events of lignocellulose degradation and wood
      colonisation. In the presence of a suitable electron acceptor, e.g. 2,6-dichloro
      indophenol, cytochrome c, or metal ions, CDH oxidises cellobiose to
      cellobionolactone. When screening 11 different Trametes spp. for the formation of
      CDH activity, all the strains investigated were found to secrete significant
      amounts of CDH when cultivated on a cellulose-containing medium. Amongst others,
      Trametes pubescens and Trametes villosa were identified as excellent, not-yet
      described, producer strains of this enzyme activity that has various potential
      applications in biotechnology. CDH from both strains was purified to apparent
      homogeneity and subsequently characterised. Both monomeric enzymes have a
      molecular mass of approximately 90 kDa (gel filtration) and a pI value of 4.2
      4.4. The best substrates are cellobiose and cellooligosaccharides; additionally,
      lactose, thiocellobiose, and xylobiose are efficiently oxidised. Glucose and
      maltose are poor substrates. The preferred substrate is cellobiose with a Km
      value of 0.21 mM and a kcat value of 22 s(-1) for CDH from T. pubescens; the
      corresponding values for the T. villosa enzyme are 0.21 mM and 24 s(-1),
      respectively. Both enzymes showed very high activity with one-electron acceptors
      such as ferricenium, ferricyanide, or the azino-bis-(3-ethyl-benzthiazolin-6
      sulfonic acid) cation radical.

PMID- 14666392
TI  - An in situ hybridization and immunofluorescence study of glycinergic receptors
      and gephyrin in the vestibular nuclei of the intact and unilaterally
      labyrinthectomized rat.
AB  - We investigated whether the expression of glycinergic receptor (GLYR) subunits of
      gephyrin and of their mRNAs in the medial vestibular nuclei are affected
      following unilateral labyrinthectomy. Specific radioactive oligonucleotide probes
      recognizing the sequences encoding alpha1-3 and ss subunits of GLYR and the
      anchoring protein gephyrin were used to probe sections of vestibular nuclei.
      Signals in these in situ hybridization experiments were detected with film or by
      emulsion photography. Animals were killed at various times following the lesion:
      5 h, 1, 3, 8, 30 and 60 days. Specific monoclonal GLYR and gephyrin antibodies
      were also used to determine GLYR and gephyrin immunoreactivity in control and
      operated rats (5 h, 1, 3 and 8 days post-lesion). In normal animals, several
      brainstem regions including the lateral, medial, superior and inferior vestibular
      nuclei contained mRNAs for gephyrin and the alpha1 and beta subunits of GLYR, and
      expressed the GLYR and gephyrin polypeptides. In unilaterally labyrinthectomized
      rats, no asymmetry was detected on autoradiographs between the two medial
      vestibular nuclei with any of the oligonucleotide probes used, or at any time
      following the lesion. No difference in the immunofluorescence staining was
      observed between the intact and deafferented medial vestibular nuclei of lesioned
      animals or between the vestibular nuclei of lesioned and controls rats. Thus,
      deafferentation of the vestibular nuclei did not affect the expression of
      gephyrin, of the various GLYR subunits, or of their mRNAs in the deafferented and
      intact medial vestibular nuclei. It is therefore unlikely that GLYR and gephyrin
      modulation contribute significantly to the recovery of the resting discharge of
      the deafferented medial vestibular neurons and consequently to the restoration of
      a normal posture and eye position.

PMID- 14666393
TI  - The role of the anterior cingulate cortex in the counting Stroop task.
AB  - The role of the anterior cingulate in the counting Stroop task was examined using
      transcranial magnetic stimulation (TMS). TMS was given over sites targeting more
      dorsal and more ventral anterior cingulate cortex and a control area of parietal
      cortex whilst subjects reported the number of words presented on the screen using
      a key press. The Stroop interference effect was abolished by TMS over both
      anterior cingulate sites. These findings support functional neuroimaging research
      which suggests that cingulate cortex is central to the processes underlying the
      Stroop task.

PMID- 14666394
TI  - The detection of tremor during slow alternating movements performed by patients
      with early Parkinson's disease.
AB  - The present study demonstrates that tremor can be detected during slow
      alternating movements (SAM) performed by patients with early Parkinson's disease
      (PD) and that its relative amplitude is strongly correlated with patients' rest
      and postural hand tremor amplitudes (Rho=0.80 and 0.61, respectively, P<0.05).
      However, the tremor detected during SAM did not influence the accuracy of
      patients because of its relatively low amplitude. These results imply that the
      presence of tremor during movement is not restricted to advanced PD, but can also
      be detected in patients with early PD having relatively low amplitude tremor.
      Evidence that the tremor detected at rest, during posture and during voluntary
      movement share similar or overlapping neural substrates is also presented.

PMID- 14666395
TI  - Vestibular influences on CA1 neurons in the rat hippocampus: an
      electrophysiological study in vivo.
AB  - Vestibular information is known to be important for accurate spatial orientation
      and navigation. Hippocampal place cells, which appear to encode an animal's
      location within the environment, are also thought to play an essential role in
      spatial orientation. Therefore, it can be hypothesized that vestibular
      information may influence cornu ammonis region 1 (CA1) hippocampal neuronal
      activity. To explore this possibility, the effects of electrical stimulation of
      the medial vestibular nucleus (MVN) on the firing rates of hippocampal CA1
      neurons in the urethane-anesthetized rat were investigated using extracellular
      single unit recordings. The firing rates of CA1 complex spike cells (n=29), which
      most likely correspond to place cells, consistently increased during electrical
      stimulation of the MVN in a current intensity dependent manner. Stimulation
      applied adjacent to the MVN failed to elicit a response. Overall, the firing
      rates of non-complex spike cells (n=22) did not show a consistent response to
      vestibular stimulation, although in some cells clear responses to the stimulation
      were observed. These findings suggest that vestibular inputs may contribute to
      spatial information processing in the hippocampus.

PMID- 14666396
TI  - Certified sediment reference materials for trace element analysis from the
      National Metrology Institute of Japan (NMIJ).
AB  - Two types of sediment reference material (NMIJ 7302-a and 7303-a) for trace
      elements analysis have been prepared and certified by the National Metrology
      Institute of Japan in the National Institute of Advanced Industrial Science and
      Technology (NMIJ/AIST). The original materials were collected from a bay near
      industrial activity in Kyushu (NMIJ CRM 7302-a; marine sediment) and from Lake
      Biwa (NMIJ CRM 7303-a; lake sediment). The sediment materials were air-dried,
      sieved, homogenized, packaged in 1000 glass bottles (60 g each), and radiation
      sterilized. Certification of these CRM for trace elements was conducted by NMIJ,
      where each element was determined by at least two independent analytical
      techniques. Isotope-dilution inductively coupled plasma mass spectrometry (ICP
      MS) was applied for certification of all the elements except mono-nuclide
      elements such as As and Co. Other techniques such as ICP-MS with quadrupole mass
      spectrometry and sector-field mass spectrometry, inductively coupled plasma
      atomic emission spectrometry (ICP-AES), and atomic absorption spectrometry (AAS),
      were also used. Certified values have been provided for 14 elements (Sb, As, Cd,
      Cr, Co, Cu, Pb, Hg, Mo, Ni, Se, Ag, Sn, and Zn) in both CRM.

PMID- 14666397
TI  - Bioassay-directed chemical analysis utilizing LC-MS: a tool for identifying
      estrogenic compounds in water samples?
AB  - A bioassay-directed chemical analysis (BDCA) scheme has been developed which
      combines a yeast screen for estrogenic activity with LC-MS detection after liquid
      liquid extraction and fractionation by size exclusion chromatography. Focusing on
      sewage-treatment plant (STP) effluents, the approach aims at characterizing the
      substances responsible for estrogenic effects in aquatic systems. Initial results
      show a strong response of STP effluent extracts in the yeast screen. Estrone,
      bisphenol A, and nonylphenol have been identified as substances being partly
      responsible for observed estrogenic activity. However, confirmation experiments
      with synthetic samples revealed that the estrogenic effect potentials of the
      samples could not be completely assigned to specific compounds. Further
      improvement of the limits of detection of the analytical scheme is needed to
      enable identification and quantification of potent estrogenic compounds at low
      concentrations.

PMID- 14666398
TI  - A high affinity ligand for GABAA-receptor containing alpha5 subunit antagonizes
      ethanol's neurobehavioral effects in Long-Evans rats.
AB  - RATIONALE: Previously, we reported that the GABA(A)receptor containing
      alpha(5)subunit played a significant role in the reinforcing actions of EtOH in
      rats selectively bred to consume alcohol. However, the role of the alpha(5)
      receptor in regulating the neurobehavioral effects of EtOH in outbred rats is not
      known. OBJECTIVE: In the present study, RY024, a novel benzodiazepine (BDZ)
      inverse agonist with high affinity (K(d) approximately 0.40 nM) and selectivity
      (approximately 67.3-fold) for the alpha(5)receptor, was investigated for its
      capacity to antagonize EtOH's reinforcing, motor impairing, and sedative effects
      in Long-Evans rats. METHODS: Rats were trained to lever press for EtOH under a
      fixed-ratio 1 schedule of reinforcement. Subsequent studies evaluated EtOH's
      motor-impairing effects in an oscillating bar task, while EtOH's sedative effects
      were measured in the open field. RESULTS: RY024 (0.125-3.5 mg/kg; IP) markedly
      reduced EtOH-maintained responding with no effects on water responding, except
      for the highest dose. RY024 (3.0-15 mg/kg; IP) also reversed the motor impairing
      effects of a moderate (0.75 g/kg), and intoxicating EtOH dose (1.25 g/kg) in the
      absence of intrinsic effects. Finally, RY024 (7.5 mg/kg) attenuated the sedation
      produced by the 1.25 g/kg EtOH dose; however, it failed to attenuate the sedation
      induced by the 0.75 g/kg EtOH dose. Given alone, RY024 exhibited intrinsic
      effects in the open field. CONCLUSION: The results suggest the GABA(A)receptor
      containing alpha(5)subtype plays an important role in regulating the reinforcing,
      motor-impairing, and sedative effects of alcohol in outbred rats.

PMID- 14666399
TI  - Paroxetine does not improve symptoms and impairs cognition in frontotemporal
      dementia: a double-blind randomized controlled trial.
AB  - RATIONALE: Patients with frontal variant frontotemporal dementia (fvFTD) present
      with disinhibition, impulsiveness, apathy, altered appetite and stereotypic
      behaviors. A non-randomized clinical trial found improvement in these symptoms
      after treatment with a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES:
      We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy
      using a double-blind, placebo-controlled experimental design. METHODS: Ten
      subjects meeting the consensus criteria for FTD were entered into a double-blind,
      placebo-controlled crossover trial. Doses of paroxetine were progressively
      increased to 40 mg daily. The same regimen was used for placebo capsules.
      Subjects were assessed with a battery of cognitive tests in the sixth week of
      paroxetine and placebo treatment. At each assessment, caregivers were interviewed
      using the Neuropsychiatric Inventory and asked to complete the Cambridge
      Behavioral Inventory. RESULTS: There were no significant differences on the
      Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine
      caused a decrease in accuracy on the paired associates learning task, reversal
      learning and a delayed pattern recognition task. There were no changes on the
      decision-making task, in spatial span, spatial recognition, spatial working
      memory, digit span and verbal fluency. CONCLUSIONS: This study finds no evidence
      for the efficacy of paroxetine in the treatment of fvFTD. The results suggest
      that a chronic course of paroxetine may selectively impair paired associates
      learning, reversal learning and delayed pattern recognition. This pattern of
      deficits closely resembles that seen after tryptophan depletion. Results are
      discussed with respect to current theories on serotonergic modulation of
      orbitofrontal/ventromedial prefrontal cortex.

PMID- 14666401
TI  - In vitro susceptibility of nocardia species to cethromycin, clarithromycin and
      amikacin.

PMID- 14666400
TI  - Long-term fracture risk following renal transplantation: a population-based
      study.
AB  - Abnormal bone metabolism is a recognized complication of end-stage renal disease,
      but fracture risk following renal transplantation has not been well quantified.
      We followed the 86 Olmsted County, Minnesota, residents who underwent initial
      renal transplantation in 1965-1995 for 911 person-years (median, 10.6 years per
      subject) in a retrospective cohort study. Fractures, and possible risk factors,
      were assessed through review of each subject's complete community medical
      records. Altogether, 117 fractures were observed during follow-up extending to 33
      years. The cumulative incidence of any fracture at 15 years was 60% versus 20%
      expected ( P<0.001). There was a significantly increased risk of fractures
      generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6-6.4] and
      vertebral (SIR, 23.1; 95% CI, 12.3-39.6) and foot fractures (SIR, 8.4; 95% CI,
      5.1-12.9) especially. Age at first transplantation, renal failure due to
      diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular
      disease and blindness were all associated with overall fracture risk. In a
      multivariate analysis, however, only age and diabetic nephropathy were
      independent predictors of fracture risk generally, while higher activity status
      was protective. Diabetes was the only independent predictor of lower limb
      fractures, whereas age and osteoporosis history predicted vertebral fractures.
      Cumulative corticosteroid dosage was not associated with increased fracture risk
      in this analysis. Despite the fact that our patients had few risk factors for
      preexisting bone disease attendant to postmenopausal osteoporosis, prior
      corticosteroid use or renal osteodystrophy, these data indicate that renal
      transplantation is associated with a significant increase in fracture risk among
      unselected patients in the community. Diabetic patients, particularly, experience
      excess lower limb fractures. Patients and their care providers should be aware of
      this elevated fracture risk, which continues long-term.

PMID- 14666402
TI  - Improvement of the diagnostic procedure in proximal myotonic myopathy/myotonic
      dystrophy type 2.
AB  - Proximal myotonic myopathy/myotonic dystrophy type 2 (PROMM/DM 2) is caused by an
      expansion of the (TG)n(TCTG)n(CCTG)n repeat tract in intron 1 of the ZNF9 gene
      located on chromosome 3q21. Because these expansions show a marked mitotic
      instability, expanded alleles are often difficult to detect. In order to improve
      the diagnostic procedure, we applied a combination of pulsed-field gel
      electrophoresis and semi-quantitative Southern blot analysis with a novel
      hybridization probe. The combination of these methods led to unequivocal results
      in about 98% of cases with a clinical diagnosis of PROMM/DM 2. Furthermore, we
      report the genotype/phenotype correlation in a patient lacking a normal ZNF9
      allele and a further proband with a "grey zone" allele.

PMID- 14666403
TI  - Genomewide linkage analysis of familial prostate cancer in the Japanese
      population.
AB  - Prostate cancer (PC) is one of the most common causes of cancer mortality in
      Western countries, and familial aggregation of PC is well known. Multiple PC
      susceptibility loci have been reported in Western countries, but attempts to
      confirm the loci in independent data sets have proven to be inconsistent. We
      performed a genomewide linkage analysis with 53 affected sib pairs to identify
      genetic loci related to PC in a Japanese population. Two linkage analyses,
      GENEHUNTER-PLUS and SIBPAL, were applied and detected nominal statistical
      significance of linkage to PC at chromosome 1p and 8p, which were reported as
      being loci for PC in Caucasians. The best evidence of linkage was detected near
      D8S550 on 8p23 (maximum Zlr=2.25, P=0.037), and the second-best evidence of
      linkage was observed near D1S2667 on 1p36 (maximum Zlr=2.24, P=0.034). This is
      the first genetic mapping of PC in Japanese, and the results suggest that
      susceptibilities to PC lie close to D8S550 on 8p23 and D1S2667 on 1p36.

PMID- 14666404
TI  - Optimum growth temperature and the base composition of open reading frames in
      prokaryotes.
AB  - The purine-loading index (PLI) is the difference between the numbers of purines
      (A+G) and pyrimidines (T+C) per kilobase of single-stranded nucleic acid. By
      purine-loading their mRNAs organisms may minimize unnecessary RNA-RNA
      interactions and prevent inadvertent formation of "self" double-stranded RNA.
      Since RNA-RNA interactions have a strong entropy-driven component, this need to
      minimize should increase as temperature increases. Consistent with this, we
      report for 550 prokaryotic species that optimum growth temperature is related to
      the average PLI of open reading frames. With increasing temperature prokaryotes
      tend to acquire base A and lose base C, while keeping bases T and G relatively
      constant. Accordingly, while the PLI increases, the (G+C)% decreases. The
      previously observed positive correlation between (G+C)% and optimum growth
      temperature, which applies to RNA species whose structure is of major importance
      for their function (ribosomal and transfer RNAs) does not apply to mRNAs, and
      hence is unlikely to apply generally to genomic DNA.

PMID- 14666407
TI  - Effect of IL-1beta microinjection into the posterior hypothalamic area on
      trigeminal nociception in the rat.
AB  - The hypothalamus has been implicated in the pathophysiology of the most disabling
      forms of primary headache, namely migraine and cluster headache. Interleukin
      1beta (IL-1beta) is highly expressed in the hypothalamus. We recorded from the
      trigeminal nucleus caudalis of rats using extracellular electrophysiological
      methods from neurons responding to electrical stimulation of the peri-middle
      meningeal artery dura mater and having receptive fields in the ophthalmic
      division of the trigeminal nerve. Data were collected from fifteen clusters of
      wide-dynamic range neurons with stable baseline firing responses between 97 and
      101% ( n=3 for each unit) to stimulation. Microinjection of IL-1beta into the
      posterior hypothalamus of 9 animals resulted in a modest inhibition of evoked
      trigeminal responses in three units, no effect in six and no overall effect for
      the entire cohort studied. The mean maximum response was a non-significant
      reduction in firing to 83+/-7% ( n=9) at 30 minutes post-injection of IL-1beta.
      There was some variation of effect dependent on site of injection with central
      posterior hypothalamus being the predominant area that resulted in inhibition.
      There was no inhibition in the six animals injected with vehicle (saline). If
      there is an important effect for IL-1beta in the posterior hypothalamus it is
      likely to be highly somatotopically restricted.

PMID- 14666406
TI  - Role of neuronal glutamate transporter in the cysteine uptake and intracellular
      glutathione levels in cultured cortical neurons.
AB  - Cysteine uptake is the rate-limiting process in glutathione synthesis. Previously
      we have shown that the inhibitors of excitatory amino acid transporters (EAATs)
      significantly enhance glutamate toxicity via depletion of intracellular
      glutathione. In this study we show evidence that the neuronal glutamate
      transporter EAAT3 is directly enrolled in cysteine uptake in cultured neurons.
      Neuronal cysteine uptake was dependent on the extracellular sodium, and was
      suppressed by EAAT inhibitors. Cysteine uptake was suppressed by extracellular
      glutamate and aspartate, substrates of EAATs, and not by substrates of cysteine
      transporters. Intracellular glutathione levels were reduced by EAAT inhibitors,
      and not by inhibitors of cysteine transporters. Knock down of EAAT3 expression
      using antisense oligonucleotide significantly reduced cysteine uptake,
      intracellular glutathione level, and neuronal viability against oxidative stress.
      These facts indicate that EAAT3 functions as a cysteine transporter, and this
      function seems to be unique and distinct from cysteine transporters that have
      been reported.

PMID- 14666408
TI  - Sciatic nerve monoaminergic system response to cold acclimatization in Muscovy
      duckling.
AB  - The effect of cold acclimatization on the monoamines in duckling sciatic nerve
      was studied. In thermoneutral (TN) ducklings, the high dopamine (DA) to
      norepinephrine (NE) ratios in the right (R, 0.14) or in the left (L, 0.20)
      sciatic nerves at 6 weeks of age suggests the presence of non-precursor specific
      dopaminergic pools. DA, DOPAC (3, 4-dihydroxyphenylacetic acid) levels and the
      ratio DA to NE were similar in cold-acclimated (CA) and TN ducklings sciatic
      nerves. Moreover, serotonin and its metabolite 5-hydroxyindoleacetic acid (5
      HIAA) remained unchanged in the sciatic nerve, indicating that this system is not
      affected with cold exposure. The contents of NE were higher (R = +44.46%; L =
      +43.73%) in sciatic nerve of CA than in TN ducklings. The results indicate that
      noradrenergic systems in the ducklings sciatic nerve are markedly affected by
      cold exposure. Interestingly, chronic exposure to cold failed to alter the
      dopaminergic and the serotonergic system in duckling sciatic nerve.

PMID- 14666409
TI  - The activity in the CNS catecholaminergic systems covaries with thyroid hormone
      metabolism in humans.
AB  - Do the CNS monoaminergic (MA) systems regulate thyroid hormone metabolism in
      humans? In 23 unmedicated, male, violent offenders without signs of thyroid
      disease, we found positive correlations between the catecholaminergic CSF
      metabolites HVA and MHPG and the peripheral T3/T4 ratio (rho=0.55, p=0.010 and
      0.51, p=0.018), indicating that increased activity in the brain MA systems,
      especially the dopaminergic, is associated with increased peripheral thyroid
      hormone activity.

PMID- 14666410
TI  - Increased striatal neuropeptide Y immunoreactivity and its modulation by
      deprenyl, clonidine and L-dopa in MPTP-treated mice.
AB  - The aim of this study was to evaluate the effect of MPTP (2 x 45 mg/kg s.c., 20 h
      apart) on striatal neuropeptide Y-like immunoreactivity (NPY-LI) in C57BL/6 mice.
      NPY-LI markedly increased 2 weeks after MPTP but it remained unchanged after 24
      h, 1 or 6 weeks. The increase in NPY-LI was accompanied by depletion of dopamine
      (-80%), DOPAC (-70%), 3-MT (-44%) and HVA (-52%). L-Deprenyl completely prevented
      the MPTP-induced NPY-LI increase, neurodegeneration of the striatal dopamine
      system and motor dysfunction. Clonidine attenuated the neurotoxin effect on NPY
      LI and dopaminergic neurons. L-dopa/carbidopa protected NPY neurons against MPTP
      but slightly enhanced MPTP-induced decrease in the levels of dopamine and its
      metabolites. The relationship between changes in NPY-LI and dopamine and
      serotonin metabolism determined by HPLC was discussed. The results further extend
      the range of MPTP-elicited modifications in striatum and demonstrate that drugs
      with antiparkinsonian activity can protect NPY neurons against MPTP toxicity.

PMID- 14666411
TI  - Switching and combining dopamine agonists.
AB  - Switching from one dopamine agonist to another is common practice in the
      treatment of patients with Parkinson's disease. This paper describes some ideas
      on the most practical way to perform switching. In addition, it describes the
      possibilities of combining various dopamine agonists and discusses pros and cons
      for doing so.

PMID- 14666412
TI  - Homocysteinemia in psychiatric disorders: association with dementia and
      depression, but not schizophrenia in female patients.
AB  - Homocysteinemia has been reported to be a risk factor for dementia, depression
      and also schizophrenia, the latter in a gender-specific manner. We have
      determined homocysteine in female inpatients suffering from various psychiatric
      diseases to further investigate a possible association between homocysteinemia
      and psychiatric disorders. Homocysteine was not elevated in schizophrenic females
      (mean, 11.6+/-5.8 micromol/l); in accordance with previous studies,
      homocysteinemia could be found frequently in dementia of different aetiology
      (mean, 17.2+/-6.7 micromol/l), but also to a slighter extent in depressive
      disorders (mean, 12.9+/-3.8 micromol/l), especially in elderly subjects. We thus
      suggest that homocysteinemia, at least in females, is an unspecific risk factor
      for organic brain disorders, but not endogenous psychoses.

PMID- 14666413
TI  - cDNA gene expression profile of rat hippocampus after chronic treatment with
      antidepressant drugs.
AB  - BACKGROUND: Chronic antidepressant treatment causes alterations in several
      hippocampal genes, which participate in neuronal plasticity. However the full
      picture of their mechanism of action is not known. The advent of genomics enables
      to identify a broader mechanism of action and identify novel targets for
      antidepressant development. METHODS: The present study examined the cDNA
      microarray gene expression profile in the hippocampus induced by chronic
      antidepressant treatment, in rats exposed to the forced swim test. Animals were
      treated for 2 weeks with moclobemide, clorgyline and amitriptyline. RESULTS: The
      three antidepressants significantly reduced immobility in the forced swim test
      and initiated significant homologous changes in gene expressions. These include
      up regulation of cAMP response element binding protein and down regulation of
      corticotrophin releasing hormone. Other gene changes noted were those related to
      neuropeptides, neurogenesis and synaptogenesis, including synaptophysin and
      neogenin. Some 89 genes were changed by at least 2 drugs, out of which 53 were
      changed oppositely by forced swim test. Confirmation of gene changes, have come
      from real time RT-PCR. CONCLUSIONS: A significant number and homology in gene
      expression were observed with the three antidepressants. Many of the genes were
      associated with neurogenesis and synaptogenesis, including synaptophysin and
      neogenin.

PMID- 14666414
TI  - Far field potentials from the brain stem after transcutaneous vagus nerve
      stimulation.
AB  - Recently, the vagus nerve has gained particular interest in neuropsychiatry, as
      neurodegenerative diseases like Alzheimer's and Parkinson's disease are supposed
      to affect the brainstem nuclei of the vagus nerve early in their course. In
      addition, electric stimulation of the vagus nerve has therapeutic effects in
      otherwise therapy-refractory epilepsies and depressions. So far, no method is
      available to assess vagus nerve function in this context. On this background and
      based on the established techniques of early acoustic evoked potentials we
      investigated if a transcutaneous electric stimulation of the sensory auricular
      branch of the vagus nerve innervating parts of the outer ear is feasible in
      healthy subjects using this hypothesis-generated approach. We were able to record
      a clear, reproducible Vagus Sensory Evoked Potential (VSEP) measured as far field
      potential probably originating in vagus nuclei in the brainstem. Further studies
      are needed to test the interindividual stability and test-retest reliability of
      this new method before potential diagnostic and therapeutic applications might be
      evaluated.

PMID- 14666415
TI  - Allelic variation in 5-HT1A receptor expression is associated with anxiety- and
      depression-related personality traits.
AB  - The 5-HT1A receptor plays a critical role in the pathophysiology of anxiety and
      depression as well as in the mode of action of anxiolytic and antidepressant
      drugs. Human 5-HT1A gene transcription is modulated by a common C-1016G single
      nucleotide polymorphism (SNP) in its upstream regulatory region. In the present
      study, we evaluated the role of the HTR1A-1019 polymorphism in the modulation of
      individual differences in personality traits by an association study of a sample
      of healthy volunteers. Personality traits were assessed with two different
      methods, NEO personality inventory (NEO-PI-R) and Tridimensional Personality
      Questionnaire (TPQ). There was a significant effect of the HTR1A-1019
      polymorphism on NEO Neuroticism with carriers of the G allele showing higher
      scores than individuals homozygous for the C variant. The effect was primarily
      due to associations with the Neuroticism facets Anxiety and Depression. Carriers
      of the G allele also exhibited higher TPQ Harm Avoidance scores. Our findings
      indicate a role of allelic variation in 5-HT1A receptor expression in the
      development and modulation of anxiety- and depression-related personality traits.

PMID- 14666416
TI  - Minimum recruitment frequency in plants with episodic recruitment.
AB  - There is concern about the lack of recruitment of Acacia trees in the Negev
      desert of Israel. We have developed three models to estimate the frequency of
      recruitment necessary for long-term population survival (i.e. positive average
      population growth for 1,000 years and < 10% probability of extinction). Two
      models assume purely episodic recruitment based on the general notion that
      recruitment in arid environments is highly episodic. They differ in that the
      deterministic model investigates average dynamics while the stochastic model does
      not. Studies indicating that recruitment episodes in arid environments have been
      overemphasized motivated the development of the third model. This semi-stochastic
      model simulates a mixture of continuous and episodic recruitment. Model analysis
      was done analytically for the deterministic model and via running model
      simulations for the stochastic and semi-stochastic models. The deterministic and
      stochastic models predict that, on average, 2.2 and 3.7 recruitment events per
      century, respectively, are necessary to sustain the population. According to the
      semi-stochastic model, 1.6 large recruitment events per century and an annual
      probability of 50% that a small recruitment event occurs are needed. A
      consequence of purely episodic recruitment is that all recruitment episodes
      produce extremely large numbers of recruits (i.e. at odds with field
      observations), an evaluation that holds even when considering that rare events
      must be large. Thus, the semi-stochastic model appears to be the most realistic
      model. Comparing the prediction of the semi-stochastic model to field
      observations in the Negev desert shows that the absence of observations of
      extremely large recruitment events is no reason for concern. However, the almost
      complete absence of small recruitment events is a serious reason for concern. The
      lack of recruitment may be due to decreased densities of large mammalian
      herbivores and might be further exacerbated by possible changes in climate, both
      in terms of average precipitation and the temporal distribution of rain.

PMID- 14666417
TI  - Species-specific measurements of ectomycorrhizal turnover under N-fertilization:
      combining isotopic and genetic approaches.
AB  - Ectomycorrhizal fungi play a significant role in the transfer of nutrients
      between plant and soil pools. Here we combine natural abundance (14)C
      measurements with restriction fragment length polymorphism (RFLP) to study the
      effects of nitrogen fertilization on the residence time of carbon within
      ectomycorrhizal species. We show that the carbon in ectomycorrhizal fungi turns
      over every 4-5 years, indicating that these fungi are relatively long-lived.
      Moreover, ectomycorrhizal fungi responded in a species-specific way to
      fertilization. Cenococcum geophilum contained younger carbon on average in
      nitrogen-fertilized plots than in control plots, even though turnover rates of
      the community as a whole did not shift significantly. Our results suggest that
      the response of ectomycorrhizal fungi to N availability is complex, and
      alterations in tissue turnover within this microbial pool may vary depending on
      community structure.

PMID- 14666418
TI  - Does flower color variation matter in deception pollinated Psychilis monensis
      (Orchidaceae)?
AB  - Negative frequency dependent selection (FDS) had been proposed as a mechanism for
      the maintenance of the high levels of variability in floral traits of rewardless
      plants. Thus far the evidence has been equivocal for discontinuous traits. We
      experimentally tested the FDS hypothesis for continuous variation in flower color
      of Psychilis monensis, a rewardless, epiphytic orchid of Mona Island, Puerto
      Rico. P. monensis flowers all year long with a peak in June and July. Plants are
      self-incompatible. Individual flowers last 9-15 days if unpollinated. Over a 9
      month observation of an unmanipulated population, a high percentage of plants
      showed pollinarium removals (79%) and fruit initiation (63%), but the actual
      percentage of flowers visited was very low (12%) and final fruit set was as low
      as the lowest recorded for orchids (2.4%). In a FDS experiment using a Latin
      Square design, we manipulated flower color in three populations. Over 50% of the
      variation in either male or female reproductive success was explained by time and
      site with no significant effect of treatment except as part of a three-way
      interaction of time x site x treatment. Paired comparisons with the controls gave
      equivocal results for both male and female measures of reproductive success.
      Major community changes had occurred during the FDS experiment with flower
      activity falling dramatically and by the third run of the experiment, only P.
      monensis was in flower. Coincidentally, the numbers of effective visits increased
      with time, presumably as pollinators became less discriminating in search of new
      food resources. Thus, negative frequency dependent selection is either sporadic
      or non-existent. Reproductive success was statistically related to locality and
      date, which was reflected in the flowering phenology of the local communities.
      High natural levels of color variation may be more influenced by drift than
      selection.

PMID- 14666419
TI  - Habitat overlap of enemies: temporal patterns and the role of spatial complexity.
AB  - Environmental heterogeneity can promote coexistence of conflicting species by
      providing spatial or temporal refuges from strong interactions (e.g., intraguild
      predation, competition). However, in many systems, refuge availability and
      effectiveness may change through time and space because of variability in habitat
      use by either species. Here I consider how the intensity of intraguild predation
      risk varies from day to night for aquatic insects that use both vegetated and
      open water habitats. Large (1,265 l) and small (42 l) mesocosms were used to test
      the hypothesis that Buenoa would choose an open-water habitat that minimized
      predation by the ambush predator Notonecta during the day, but that at night
      Buenoa would safely use both vegetated and open water. Regardless of container
      size, Notonecta remained in vegetated water during the day and exploited both
      habitats at night, despite exhibiting greatest instantaneous predation rates in
      open water during the day. In contrast, Buenoa maintained an even distribution
      throughout the mesocosms during day and night, even though habitat-specific
      predation risks were fivefold lower in open waters than in vegetation during the
      day and habitat-specific predation risk would have been reduced threefold by
      fully exploiting open waters. Thus, temporal heterogeneity was both beneficial
      and detrimental to Buenoa; darkness of night reduced predation, but spatial
      refuges also disappeared. Together, these patterns suggest that while
      environmental heterogeneity can dampen intense biotic interactions, enemies do
      not select habitats solely on the basis of conflict avoidance. Instead, it
      appears that habitat-specific variation in other biotic (e.g., visual predators)
      or physical factors (e.g., UV radiation) may also mediate species interactions by
      influencing habitat selection.

PMID- 14666420
TI  - Expressing leaf water and cellulose oxygen isotope ratios as enrichment above
      source water reveals evidence of a Peclet effect.
AB  - There is an increasing ecological interest in understanding the gradients in
      H(2)(18)O enrichment in leaf water (i.e. a Peclet effect), because an
      appreciation of the significance of the Peclet effect is important for improving
      our understanding of the mechanistic processes affecting the (18)O composition of
      leaf water and plant organic material. In data sets where both source water and
      leaf water (18)O data are available, we can evaluate the potential contribution
      of a Peclet effect. As an example, we recalculate data published earlier by Roden
      and Ehleringer (1999, Oecologia 121:467-477) as enrichments in leaf water
      (Delta(L)) and cellulose (Delta(cell)) above source water. Based on these
      recalculations, we present support for the relevance of a Peclet effect in
      leaves. Further, we demonstrate that the subtle variations in Delta(L) and
      Delta(cell) caused by a Peclet effect may be masked in experimental systems in
      which variation in the source water oxygen isotope ratio is considerable.

PMID- 14666421
TI  - Non-methylated Genomic Sites Coincidence Cloning (NGSCC): an approach to large
      scale analysis of hypomethylated CpG patterns at predetermined genomic loci.
AB  - We have developed a new approach to the analysis of hypomethylated CpG patterns
      within predetermined, megabase long, genome regions. The approach, which we term
      Non-methylated Genomic Sites Coincidence Cloning (NGSCC), includes three main
      steps. First, total genomic DNA is digested with a methylation sensitive
      restriction endonuclease, such as HpaII or HhaI. Then the fragments corresponding
      to the genomic area of interest are selected. To this end the fragmented genome
      DNA is hybridized with a mixture of clones (BACs, cosmids etc.) representing a
      given region and digested with the same restriction enzyme(s). A special version
      of the coincidence cloning procedure was developed to make this hybridization
      selection highly efficient and specific. Finally, fragments of the locus under
      study are mapped and sequenced. The technique proved to be efficient and
      specific. As a test, it was applied to the analysis of hypomethylated CpG
      patterns along the 1-Mb D19S208-COX7A1 (Chr 19q13.12) locus, on human chromosome
      19, in normal testis and in seminoma tissues. Some differences in the
      distribution of hypomethylated CpGs between the two tissues were demonstrated.
      The methylation profiles in both tissues revealed a clear trend to clustering of
      non-methylated sites. We also analyzed the expression of genes located within
      hypomethylated clusters in both tissues. It was shown that, whereas the
      expression of some of the genes investigated was correlated with hypomethylation
      of the region, other genes were expressed regardless of their methylation status.
      NGSCC thus promises to be a useful approach for the analysis of the role of
      dynamic epigenetic factors in genome function.

PMID- 14666422
TI  - Activation of flavonoid biosynthesis by solar radiation in bilberry ( Vaccinium
      myrtillus L) leaves.
AB  - The effect of solar radiation on flavonoid biosynthesis was studied in bilberry (
      Vaccinium myrtillus L.) leaves. Expression of flavonoid pathway genes of bilberry
      was studied in the upper leaves of bilberry, exposed to direct sunlight, in the
      shaded leaves growing lower in the same plants and in fruits. Bilberry-specific
      digoxigenin-dUTP-labeled cDNA fragments of five genes from the general
      phenylpropanoid pathway coding phenylalanine ammonia-lyase and from the flavonoid
      pathway coding chalcone synthase, flavanone 3-hydroxylase, dihydroflavonol 4
      reductase, and anthocyanidin synthase were used as probes in gene expression
      analysis. Anthocyanins, catechins, proanthocyanidins, flavonols and
      hydroxycinnamic acids from the leaves and fruits were identified and quantified
      using high-performance liquid chromatography combined with a diode array
      detector. An increase in the expression of the studied flavonoid pathway genes
      was observed in leaves growing under direct sun exposure. Also, the
      concentrations of anthocyanins, catechins, flavonols and hydroxycinnamic acids
      were higher in the leaves exposed to direct sunlight. However, the concentration
      of polymeric procyanidins was lower in sun-exposed leaves, whereas that of
      prodelphinidins was slightly increased. The results give further support for the
      protective role of flavonoids and hydroxy cinnamic acids against high solar
      radiation in plants. Also, the roles of different flavonoid compounds as a
      defense against stress caused by sun exposure is discussed.

PMID- 14666424
TI  - Aerobic determinants of the decline in preferred walking speed in healthy, active
      65- and 80-year-olds.
AB  - The preferred walking speed is a common measure of mobility that declines with
      age and has been related to maximal oxygen uptake (VO(2,max)). The present study
      determined whether this decline is associated with a higher percentage of the
      ventilatory threshold in older adults walking at their preferred speed. We
      compared the preferred walking speed and VO2 at this speed in relation to both
      VO(2,max) and VO2 corresponding to the ventilatory threshold (TVE) in healthy,
      physically active sexagenarians (G65, n=10) and octogenarians (G80, n=10) walking
      on a treadmill. The preferred walking speed was lower in G80 (1.16+/-0.09 m.s(
      1)) than in G65 (1.38+/-0.09 m.s(-1); P<0.001). Energy expenditure and the energy
      cost of walking at the preferred walking speed were not significantly different
      between the two groups. G80 subjects exhibited significantly higher fractions of
      VO(2,max) (60.8+/-8.0%) and TVE (74.2+/-7.9%) at the preferred walking speed than
      G65 (42.9+/-5.0 and 53.2+/-5.7% respectively; P<0.001). Multiple regression
      analysis showed that the fraction of TVE was the main determinant, with a small
      contribution of height, in the decline in the preferred walking speed in healthy
      and active elderly subjects (R2=64%; P<0.001). These findings show that with age,
      walking at the preferred speed requires a higher fraction of TVE. This increase
      in the relative physiological effort at preferred walking speed could explain the
      reduction in this gait speed in healthy older subjects.

PMID- 14666423
TI  - Up-regulation of Arabidopsis thaliana NHL10 in the hypersensitive response to
      Cucumber mosaic virus infection and in senescing leaves is controlled by
      signalling pathways that differ in salicylate involvement.
AB  - The Arabidopsis thaliana (L.) Heyhn. genome contains 45 genes that show
      substantial sequence similarity to the tobacco ( Nicotiana tabacum L.) HIN1
      (harpin-induced) gene and the Arabidopsis NDR1 (non-race-specific disease
      resistance) gene. Of these, the nine ( NHL1 to NHL3, NHL8 to NHL12 and NHL22)
      that bear the highest identity to HIN1 were selected and their expression in
      various situations was examined. We found that NHL10 behaves like the tobacco
      HIN1 gene in that its transcripts are abundant in senescing leaves and they
      specifically accumulate during the hypersensitive response (HR) caused by
      exposure to an avirulent Cucumber mosaic virus (CMV) strain. Spermine, a novel
      inducer of tobacco PR (pathogenesis-related) genes, was found to up-regulate
      expression of NHL3, NHL10 and NDR1. Green fluorescent protein-fusion experiments
      indicated that NHL2 and NHL10, and possibly NDR1 are localized in the
      chloroplasts. Studies using Arabidopsis mutants defective in salicylic acid (SA),
      ethylene and jasmonic acid signalling revealed that the senescence-associated
      expression of NHL10 is mediated by a pathway that involves SA but that NHL10
      expression during CMV-induced HR and spermine treatment is totally independent of
      SA.

PMID- 14666425
TI  - High efficiency degradation of tetrahydrofuran (THF) using a membrane bioreactor:
      identification of THF-degrading cultures of Pseudonocardia sp. strain M1 and
      Rhodococcus ruber isolate M2.
AB  - A mixed microbial culture capable of growing aerobically on tetrahydrofuran (THF)
      as a sole carbon and energy source was used as the inoculum in a 10 l working
      volume membrane bioreactor. Following start-up, the reactor was operated in batch
      mode for 24 h and then switched to continuous feed with 100% biomass recycle. On
      average, greater than 96% of THF fed to the reactor was removed during the 8
      month study. THF loading rates ranged from 0.62 to 9.07 g l(-1) day(-1) with a
      hydraulic retention time of 24 h. THF concentrations as high as 800 mg/l were
      tolerated by the culture. Biomass production averaged 0.28 kg total suspended
      solids/kg chemical oxygen demand removed, i.e., comparable to a conventional
      wastewater treatment process. Periodic batch wasting resulted in a solids
      retention time of 7-14 days. Reactor biomass typically ranged from 4 to 10 g/l
      volatile suspended solids and the effluent contained no solids. Pure THF
      degrading cultures were isolated from the mixed culture based on morphological
      characteristics, Gram-staining and THF degradation. Based on 16S rDNA analysis
      the isolates were identified as Pseudonocardia sp. M1 and Rhodococcus ruber M2.

PMID- 14666426
TI  - DNA vaccines for cancer.
AB  - Immunotherapy has become a potentially feasible strategy for the control of
      cancers; the goal of cancer vaccines is to achieve this via tumor antigen
      specific humoral or cell-mediated immunity, as well as via innate immunity. DNA
      vaccines have become important immunotherapeutic agents for combating cancers due
      to their simplicity and safety, and their capacity for repeated administration.
      Continuing progress in our understanding of how professional antigen-presenting
      cells orchestrate immune responses provides a framework from which to design more
      effective DNA vaccines. To this end, innovative strategies to enhance DNA vaccine
      potency have been developed, including the modification of enhancement of antigen
      delivery, antigen processing, manipulation of apoptosis, and anti-angiogenic
      strategies. Furthermore, strategies for breaking immune tolerance to endogenous
      tumor-associated antigens have begun to be developed. These advances in DNA
      vaccine technology have led to significant results in preclinical tumor models,
      prompting the execution of a number of clinical trials of DNA vaccines for
      cancer. If these trials prove DNA vaccines to be clinically effective, they could
      lead to the development of a new generation of therapies for the treatment and/or
      prevention of cancer.

PMID- 14666427
TI  - New perspectives in the pharmacotherapy of erectile dysfunction.
AB  - Current classification of pharmacological treatments for erectile dysfunction
      distinguishes between central and peripheral "initiators" and "conditioners" of
      erection. However, such taxonomy does not take into account the impact on the
      couple, the ultimate recipient of the treatment. For this reason, we propose here
      a new, couple-based sexological taxonomy, which divides pharmacotherapies into
      "harmonious" and "non-harmonious". New treatments and more effective drugs are
      expected in the near future because of the rapid expansion of research into
      erection regulation mechanisms and epidemiological studies.

PMID- 14666428
TI  - Neuroprotection against hypoxia-ischemia by insulin-like growth factor-I (IGF-I).
AB  - Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that has been
      investigated as a potential neuroprotective drug for the treatment of stroke and
      other forms of neural damage. Preclinical studies over the last decade have
      demonstrated that IGF-I and some of its fragments can protect against neuronal
      and glial cell degeneration in animal models of stroke such as hypoxia-ischemia.
      Although the results to date are encouraging, the size of the IGF-I molecule has
      proved problematic and has led researchers to investigate routes of
      administration that bypass the blood-brain barrier, such as intranasal
      application, or to focus on fragments of IGF-I, such as the N-terminal peptide
      Gly-Pro-Glut (GPE). While the results of these studies have also been positive,
      systematic dose-response comparisons with recognized neuroprotectants have not
      yet been published, the time window for therapeutic effects is not yet clear and
      long-term functional studies have not been conducted.

PMID- 14666429
TI  - NicVAX (Nabi Biopharmaceuticals).
AB  - Nabi Biopharmaceuticals is developing NicVAX, a proprietary vaccine designed as a
      potential therapeutic to prevent and treat nicotine addiction.

PMID- 14666430
TI  - EPO-906 (Novartis).
AB  - Novartis Pharma AG is developing EPO-906, an intravenous formulation microtubular
      depolymerization inhibitor (microtubule stabilizer), for the potential treatment
      of cancer.

PMID- 14666431
TI  - RDP-58 (SangStat Medical).
AB  - RDP-58, a decapeptide with inhibitory effects on tumor necrosis factor synthesis,
      is under development by SangStat Medical Corp for the potential treatment of
      Crohn's disease and ulcerative colitis; phase II trials for both these
      indications commenced in October 2001. SangStat also initiated a phase I trial in
      chemotherapy-induced diarrhea in the first quarter of 2003 and anticipates
      initiating phase I trials in the gastrointestinal complications of HIV by the end
      of 2003.

PMID- 14666432
TI  - [Evidence based evaluation of conservative treatment options for patellar
      tendinitis syndromes].
AB  - INTRODUCTION: Patellar tendinopathy causes substantial morbidity in both
      professional and recreational athletes. There is no consensus about conservative
      treatment strategies for this condition. METHODS: With the help of the evidence
      based medicine method it is estimated whether conservative treatment is
      appropriate for treating pain in this condition. RESULTS: 5 specialist articles
      that matched the clinical question were found in medical databases. One article
      was analyzed for clinical relevance. The evaluation showed that physiotherapeutic
      treatment of pain in combination with additional iontophoresis is more promising
      than physiotherapy alone. DISCUSSION: Current evidence suggests that traditional
      physiotherapy should be combined with additional therapeutic treatment. This
      requires further randomized prospective, placebo-controlled trials in order to
      confirm its efficiency. Prognostic effects of treatments should be included into
      these studies.

PMID- 14666433
TI  - [Efficacy of stairclimber for muscle strengthening in a closed system after
      anterior cruciate ligament reconstruction].
AB  - In a prospective study we investigated the value regarding muscle strength of two
      stairclimbers with either coupled or non-coupled pedals at either high or low
      stepping frequency. Following autologous patellar tendon graft surgery 14
      patients for each group completed a strict exercising program. After 6 weeks of
      training a clear advantage was found for the group stepping at low speed with
      coupled pedals when measuring: At 60 degree/s the average maximum torque of
      extension increased from 37.7 to 61.7% as compared to a control group (30 to
      47.2%). Analogous the percent ratio of flexion/extension (H/Q ratio) improved
      significantly. During the second training period the improvement of the extension
      strength as well as the H/Q ratio was found to be only marginal. No negative
      effects of this type of training on ligament stability could be detected.
      CONCLUSIONS: Regarding a faster recovery of muscle strength and the improvement
      of the intermuscular coordination, the stairclimber training, beginning with week
      7 after surgery and lasting over a period of 6 weeks, is considered advantageous,
      especially when exercising is done at low speed and with coupled pedals.

PMID- 14666434
TI  - [Arthroscopy for anterior joint pathology at the upper ankle joint -
      pathogenesis, therapy and results].
AB  - The conservative treatment of chronic ankle pain and at the so-called
      "footballer's joint" is of limited success. Arthroscopy is a possibility of
      operative treatment. 25 arthroscopies were carried out at the upper ankle joint
      at anterior joint pathology from January 1998 to June 1999. 21 patients could be
      examined in a median follow-up of 16 months (4-24). The median age was 31 years
      (17-56; female: 6, male: 15). Synovilitis was found in all cases. In 9 cases
      exophytes of the tibia, in 10 cases osteochondral lesions and in 7 cases antero
      lateral impingement ware seen. The preoperative Score of Mazur of median 63 (21
      85) points showed a significant raise (p < 0.05) in follow-up to median 93 (81
      100) points. The complete athletic rehabilitation could be restored in 2/3 of the
      patients. The conservative therapy represents a good method of treatment chronic
      troubles in the upper ankle joint. Arthroscopy is indicated if no recovery can be
      attained.

PMID- 14666435
TI  - [Impingement lesion of the distal anterior Achilles tendon in sub-Achilles
      bursitis and Haglund-pseudoexostosis-a therapeutic challenge].
AB  - Retrocalcaneal bursitis in athletes is frequently misdiagnosed. Results of
      conservative treatment are not very promising. This investigation evaluates the
      results of 39 consecutive cases in 38 patients surgically treated due to chronic
      retrokalkaneal bursitis in a sport specific population. Preoperative MRI and
      ultrasound investigation showed corresponding lesions (focal degeneration,
      partial rupture) of the anterior Achilles tendon. This is possibly the result of
      a previously undescribed impingement lesion produced by the Haglund's bone and
      the chronically inflamed retrocalcaneal bursa. During operation this lesion was
      additionally addressed in 85% of the cases. Follow up was done after 32 months.
      Success rate was 54%. VISA-A Score at follow up was 80.6 points. Training and
      competition activities were started at 16 weeks and 9 months respectively.
      Unsatisfying results were analysed. In two cases Haglund's bone resection was
      incomplete and had to be removed in a reoperation. Additionally one deep wound
      infection had to be revised. Due to the distal Achilles tendon fiber extensions
      around the medial and lateral calcaneal bone, an unintended Achilles tendon
      lesion, induced by the edge of the osteotome seems to be possible. Two calcanear
      stress fractures complicated the postoperative rehabilitation.

PMID- 14666436
TI  - [Concerning the language in our discipline].

PMID- 14666437
TI  - [Alcohol--a perioperative problem of anaesthesia and intensive care medicine].
AB  - Alcohol is a socially tolerated drug. Its consumption is associated with several
      physiological and pharmacological negative side-effects during anaesthesia and
      intensive care. The impact of chronic and acute alcoholism on perioperative
      morbidity and mortality and especially on anaesthetic risk are important, due to
      pharmacological interactions, pathophysiological changes and direct
      pharmacological interactivities between alcohol and narcotics. In contrast to
      opioid withdrawal symptoms of alcohol withdrawal are a serious and potentially
      life-threatening complication and should be avoided or the risk for occurrence
      must at least be reduced. Patients with a high risk of developing perioperative
      symptoms of alcohol withdrawal can be detected by laboratory tests and
      questionnaires. A prophylaxis of withdrawal should be started preoperatively
      solely with benzodiazepines or in combination with clonidine. Haloperidol is the
      drug of choice for emerging symptoms of alcohol withdrawal with productive
      psychosis. To estimate the pharmacological changes during anaesthesia, it is
      necessary to differentiate whether the patient is an occasional drinker with
      acute intoxication, a chronic abuser without limitations of hepatic function or a
      chronic user with insufficiency of the liver. The most important implication for
      anaesthesia are the choice of a rapid sequence induction to reduce the risk of
      aspiration and the maintenance of haemodynamic stability and liver perfusion. For
      the acute alcoholic providing prolonged postoperative surveillance is necessary,
      for the chronic alcoholic intensive care seems to be mandatory. For regional
      anaesthesia the indications and limitations are the same as for other patients
      (cooperativeness, coagulation, consent, etc.).

PMID- 14666438
TI  - [Phantom limb pain: aspects of neuroplasticity and intervention].
AB  - Phantom-limb pain is a common sequel of amputation, occurring in up to 80 % of
      the amputee population. It must be differentiated from non-painful phantom
      phenomena, residual-limb pain, and non-painful residual-limb phenomena. A
      comprehensive model of phantom-limb pain is presented that assigns a major role
      to pain occurring before the amputation and to central as well as peripheral
      changes related to it. Special emphasis is put on the role of cortical
      reorganization in the development of phantom limb pain. Finally, new approaches
      to the prevention and treatment of phantom limb pain are presented that have a
      positive influence on phantom limb pain by preventing or reversing cortical
      reorganization.

PMID- 14666439
TI  - [Ketamine attenuates the contractile response to vasoconstrictors in isolated
      coronary artery rings].
AB  - OBJECTIVE: Ketamine was shown to increase coronary blood flow. It was the aim of
      this study to answer the question whether ketamine directly dilates coronary
      arteries. METHODS: Using the model of isolated vessel rings we studied the
      effects of ketamine (2.5, 25, and 250 microg ml(-1)) on the contractile response
      to three vasoconstrictors, acetylcholine, histamine, and serotonin in porcine
      coronary artery segments. Other rings were contracted with KCl or PGF (2a) and
      then treated with ketamine (5 up to 500 microg ml(-1) added cumulatively).
      RESULTS: Ketamine dose-dependently dilated coronary arteries in concentrations
      beyond those used in clinical practice. In intact rings ketamine racemate (250
      microg ml(-1)) attenuated contractions mediated by acetylcholine by 38.8 +/-
      2.8%, histamine by 33.0 +/- 4.4% and serotonin by 42.1 +/- 3.7% (p < 0.05). There
      were no differences between intact and denuded rings (acetylcholine 38.5 +/-
      2.8%, histamine 26.6 +/- 4.7%, serotonin 30.0 +/- 3.2%). With low concentrations
      of ketamine (2.5 microg ml(-1)) a slight tendency towards a contraction was
      recorded (n. s.). In rings precontracted with either KCl or PGF (2a) ketamine
      caused a small enhancement of contraction (KCl: 101.4 +/- 0.4%, PGF (2a): 101.3
      +/- 1.4%) when administered in low concentration (5 microg ml(-1)), but almost
      complete relaxation (KCl: 0.4 +/- 1.3%, PGF (2a): 0.0 +/- 5.4%) in high
      concentration (500 microg ml(-1)). CONCLUSIONS: It is concluded that ketamine
      dose-dependently dilates porcine coronary arteries in concentrations beyond those
      used in clinical practice and that this effect is independent of endothelial
      function.

PMID- 14666440
TI  - [Comparison of premedication with clonidine and midazolam combined with TCI for
      orthopaedic shoulder surgery].
AB  - OBJECTIVE: The most frequently used drugs for premedication are benzodiazepines
      and alpha (2)-adrenoceptor agonists. In this study we examined midazolam and
      clonidine for premedication in combination with target controlled infusion
      anaesthesia (TCI) in patients undergoing orthopaedic shoulder surgery and
      analysed the effects on the peri- and postoperative course. METHODS: Forty-five
      Patients (ASA I-III) were included in this prospective randomized, double blind
      study. Sixty minutes prior to anaesthetic induction the patients received
      clonidine in a dosage of 2 microg x kg(-1) (group ND) or 5 microg x kg(-1) (group
      HD) or 0.1 mg x kg(-1) midazolam (group midazolam) per orally. Anaesthesia was
      performed as TCI with propofol (plasma concentration 2.0-4.0 microg x ml(-1)) und
      remifentanil (plasma concentration 0.2-0.4 microg x ml(-1) x min(-1)). 15 minutes
      before the operation was finished, all patients received a bolus dose of 0.1 mg x
      kg(-1) piritramid i.v., followed by administration of piritramid via a PCA pump
      (patient controlled analgesia) for a duration of 24 hours. During the time of the
      operation the influence of premedication on the anaesthetic course was determined
      by vital parameters and ranking scales. For statistic evaluation we used the
      Kruskal-Wallis test, ANOVA with Tukey as post hoc test and the test named after
      Fisher (p < 0.05). RESULTS: The effects of premedication on haemodynamic
      parameters and ranking scales for sedation as well as anaesthetic requirements
      were comparable in all three groups. In the postoperative period the incidence of
      postoperative nausea and vomiting (PONV) (ND: n = 8, HD: n = 2, midazolam: n = 6)
      and the use of pritramid were lower in the clonidine HD group (HD: 38.7 +/- 30.7
      mg, ND: 51.7 +/- 25.1 mg, midazolam: 45.1 +/- 30.4 mg) than in the other groups.
      CONCLUSIONS: Premedication with the alpha(2)-adrenoceptor agonist clonidine is as
      good as with benzodiazepines in combination with TCI. Because of the lower
      incidence of PONV and the need of piritramid in the postoperative period patients
      premedicated with 5 microg x kg(-1) clonidine may benefit from this
      premedication.

PMID- 14666441
TI  - [Effects of esmolol- and sodium nitroprusside-induced controlled hypotension on
      hepatocellular integrity in patients undergoing endonasal sinus surgery].
AB  - BACKGROUND: Controlled hypotension (CH) is an established method to reduce
      intraoperative bleeding. The aim of the study was to investigate the influence of
      CH induced by sodium nitroprusside (SN) or esmolol on hepatocellular integrity.
      METHODS: Prospective, randomized, controlled study. 45 patients scheduled for
      elective endonasal sinus surgery were allocated to one of the following three
      groups: 1. SN-group (n = 15): CH induced by SN. 2. Esmolol-group: CH induced by
      esmolol. In both groups mean arterial pressure was kept between 50-55 mmHg. 3.
      Control group (n = 15): no hypotension was performed (MAP > 70 mmHg). The
      cytosolic liver enzyme alpha-glutathione S-transferase (alpha-GST) and standard
      liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma
      glutamyltransferase) were measured at the following timepoints: preoperative
      (T0), at the end of surgery (T1), 2 h (T2), 24 h (T3) and 48 h (T4)
      postoperatively. RESULTS: alpha-GST concentrations were significantly higher in
      patients receiving CH (SN: 5.9 +/- 3.4; Esmolol: 6.5 +/- 2.8 microg/L) in
      comparison with controls (2.5 +/- 1.4 microg/L) at T1. Already at T2 there were
      no significant differences between the three groups. Standard liver enzymes
      showed a similar course in all groups. CONCLUSION: The small but significant
      increase of alpha-GST in both hypotension groups suggests that hypotension
      induces a mild damage of hepatocellular integrity.

PMID- 14666442
TI  - [Analysis of ventricular fibrillation signals for the evaluation of
      defibrillation success in the treatment of ventricular fibrillation].
AB  - OBJECTIVE: Precise detection of ventricular fibrillation (VF), reliable
      prediction of defibrillation success and adjustment of the discharge waveform to
      the patient's transthoracic impedance may contribute to a reduction of
      electricity-associated myocardial injury caused by unnecessary counter shocks.
      Specifically, asystole thresholds distinguish between VF and asystole, and thus
      prevent unnecessary defibrillation attempts. We reviewed various studies and
      manufacturer characteristics regarding the parameters and algorithms for
      analyzing arrhythmia ECG signals. METHODS: Asystole threshold values of several
      defibrillator manufacturers were collected and a literature review was performed
      including the following parameters: amplitude, frequency, bispectral analysis,
      amplitude spectrum area, wavelets, nonlinear dynamics, N(alpha)histograms, and
      combinations of various parameters. RESULTS: The manufacturer dependent asystole
      thresholds vary substantially. We show ways to optimize an ECG-based analysis for
      the next technological generation of defibrillators. During advanced cardiac life
      support (ACLS) the probability of defibrillation success should be estimated.
      Optimal defibrillation waveform, depending on transthoracic resistance, should be
      individually determined. In case of prolonged VF with a low ECG amplitude
      defibrillation should not be attempted unless coronary perfusion has been
      improved by further measures of ACLS. The combined evaluation of VF amplitude and
      frequency is effective in predicting defibrillation success. Estimation of
      further parameters is potentially useful for guiding optimal timing of
      defibrillation. At present, the implementation of most parameters in out-of
      hospital cardiopulmonary resuscitation (CPR) is limited by the lack of technical
      feasibility of online computing. CONCLUSION: Analysis of VF ECG signals should
      allow adequate VF detection as well as prediction of defibrillation success.
      Suitable asystole thresholds for analysis of ECG signals have to be determined,
      and the adverse effects of CPR associated artefacts on data analysis have to be
      reduced. Analysis of VF ECG signals is a precondition of individually optimized
      defibrillation and may contribute substantially to an increased quality of CPR.

PMID- 14666443
TI  - [Possible intubation difficulties after cricotracheal resection--a casuistry].
AB  - Since the 1960s neonatal intensive care therapy made great progress. Along with
      the new possibilities of treatment unknown complications occurred especially in
      the upper respiratory tract. To relieve these respiratory complications new
      surgical techniques were developed in the 1980s. Children that were successfully
      operated on may now present to an anesthetist as a teenager or young adult. The
      serious anatomic deviations may cause unexpected problems during the induction of
      anesthesia. This casuistry will show a possible algorithm that may keep patient
      and physician save from difficulties and surprises.

PMID- 14666444
TI  - [Pro: Thoracic epidural catheter in postoperative pain treatment].

PMID- 14666445
TI  - [Con: Thoracic epidural catheter in postoperative pain treatment].

PMID- 14666446
TI  - The breakpoint region of the most common isochromosome, i(17q), in human
      neoplasia is characterized by a complex genomic architecture with large,
      palindromic, low-copy repeats.
AB  - Although a great deal of information has accumulated regarding the mechanisms
      underlying constitutional DNA rearrangements associated with inherited disorders,
      virtually nothing is known about the molecular processes involved in acquired
      neoplasia-associated chromosomal rearrangements. Isochromosome 17q, or "i(17q),"
      is one of the most common structural abnormalities observed in human neoplasms.
      We previously identified a breakpoint cluster region for i(17q) formation in
      17p11.2 and hypothesized that genome architectural features could be responsible
      for this clustering. To address this hypothesis, we precisely mapped the i(17q)
      breakpoints in 11 patients with different hematologic malignancies and determined
      the genomic structure of the involved region. Our results reveal a complex
      genomic architecture in the i(17q) breakpoint cluster region, characterized by
      large ( approximately 38-49-kb), palindromic, low-copy repeats, strongly
      suggesting that somatic rearrangements are not random events but rather reflect
      susceptibilities due to the genomic structure.

PMID- 14666447
TI  - Tracheoplasty for long segment congenital tracheal stenosis: analysis of 29
      patients over two decades.
AB  - PURPOSE: The authors determined the long-term outcome of patients who underwent
      surgical repair of long-segment congenital tracheal stenosis (LCTS) and compared
      the quality of cartilage graft and slide tracheoplasty techniques. METHODS:
      Twenty-nine patients underwent surgical repair of LCTS at 29 days to 9 years of
      age. In 26 patients, more than 50% of the entire length of the trachea was
      involved. The early 12 patients (1981 through 1992) were treated with a costal
      cartilage graft for tracheal reconstruction. The remaining 17 patients (1997
      through 2002) were treated with slide tracheoplasty. For both procedures, a
      median sternotomy was preferred because of convenience when using extracorporeal
      circulation and for simultaneous repair of associated cardiovascular anomalies.
      RESULTS: Of the 12 patients who underwent a costal cartilage graft, 8 survived
      (66%). Six of these patients are free of disease, but 2 have persistent airway
      problems. Three patients died of residual stenosis and 1 of unrelated disease. Of
      the 17 patients who underwent slide tracheoplasty, 13 survived (76%), and 10 are
      free of disease. Three patients continue to require a stent because of
      tracheomalacia and granulation. Two patients died of cardiac failure, 1 of
      granulation, and 1 of aspiration pneumonia. CONCLUSIONS: The authors challenged
      LCTS with a unique surgical approach and succeeded in making an incurable disease
      curable. When the cartilage graft technique is compared with slide tracheoplasty,
      however, the latter is preferable because it preserves native tracheal tissue
      with less frequent complications.

PMID- 14666448
TI  - Transplantation of the cryopreserved tracheal allograft in growing rabbits.
AB  - BACKGROUND: Surgical treatment of the congenital tracheal stenosis is
      challenging, and the long-term fate of transplanted tracheal allograft remains
      unclear. The authors evaluated the morphologic changes of the cryopreserved
      tracheal allograft after transplantation in a growing rabbit model. METHODS: Each
      allograft (n = 7) was harvested from 90- to 120-day-old Japanese rabbits,
      immersed in the preservation solution, and stored in a programmable freezer until
      reaching -80 degrees c and then kept in liquid nitrogen for 1 week. Orthotopic
      tracheal transplantation of 7 tracheal rings in an end-to-end fashion was
      performed in age-matched young rabbits without immunosuppression. The grafts were
      assessed at 1 week, 1 month, and 3 months after transplantation. As controls,
      fresh autografts also were evaluated after the same procedure. RESULTS: Two
      animals died of pneumonia. The body weight gain was similar in both groups. All
      grafts were patent, but no allografts showed normal growth in length or diameter.
      Microscopic findings of the allograft showed calcification of the tracheal
      cartilage without infiltration of inflammatory cells and marked lymphocyte
      proliferation in the subepithelium. CONCLUSIONS: Cryopreserved tracheal
      allografts without immunosuppressant showed favorable patency of the trachea at 3
      months; however, no growth of the allograft occurred in this animal model. The
      problem of calcification of the allograft remains to be solved.

PMID- 14666449
TI  - Endoscopic balloon dilatation of esophageal strictures in infants and children:
      17 years' experience and a literature review.
AB  - PURPOSE: Whereas endoscopic balloon dilatation (EBD) of benign esophageal
      strictures is an established mode of therapy in adults, this has not been
      accepted universally in the pediatric population. The aim of this study is to
      report the safety, efficacy, and long-term results of EBD for children in the
      authors' center. METHODS: Between 1986 and 2002, a total of 77 children (median
      age, 1.8 years; range, 2 months to 20 years) were treated by EBD for various
      causes: 2 had achalasia, and 75 had esophageal strictures (postesophageal atresia
      repair, 63; reflux esophagitis, 7; postfundoplication, 2; caustic injury, 3).
      Dilatations were performed using flexible endoscopy and fluoroscopic screening
      under general anesthesia. RESULTS: A total of 260 dilatations were carried out
      with the mean number of EBD per patient being 3.4 (range, 1 to 19). A mean period
      of 5 months (maximum, 28 months) for each patient was required. Four
      complications of esophageal perforations (1.5%) were observed, but only one
      required surgical repair because of persistent leakage. The remaining patients
      have undergone long-term follow-up (median follow-up, 6.6 years), and all are
      asymptomatic. CONCLUSIONS: This large series has shown that EBD can provide a
      safe and effective mean of relieving esophageal strictures with good long-term
      results.

PMID- 14666450
TI  - Esophageal motor function in congenital esophageal stenosis.
AB  - BACKGROUND/PURPOSE: Congenital esophageal stenosis (CES) is a rare condition that
      is associated with various foregut symptoms. The aim of the current study was to
      investigate esophageal motor function in pediatric patients with isolated CES.
      METHODS: Four boys with CES (age, 3 weeks to 4 years old) were studied before
      treatment. The initial symptoms were dysphagia or stridor. The CES was caused by
      fibromuscular stenosis (FMS) in 2, tracheobronchial remnants (TBR) in 1, and
      membranous diaphragm (MD) in 1. An esophagram, endoscopy, 24-hour esophageal pH
      monitoring, and manometry were conducted. RESULTS: The esophagram showed the
      stasis of contrast medium proximally to the distal esophageal narrowing in
      FMS/TBR patients. Endoscopic esophagitis was not found in any patients. Three
      patients were documented with pathologic esophageal acid exposure by 24-hour
      esophageal pH monitoring. Manometry showed that esophageal contractions
      predominantly were synchronous in FMS/TBR patients but were peristaltic in an MD
      patient. Basal lower esophageal sphincter (LES) pressure was at least 20 mm Hg in
      all. Swallow-induced LES relaxations were incomplete in FMS/TBR patients.
      CONCLUSIONS: The presence of gastroesophageal reflux and impaired esophageal
      motility are common in patients with CES.

PMID- 14666451
TI  - Anterior approach bilateral musculomucosal flaps repair for
      laryngotracheoesophageal clefts.
AB  - Laryngotracheoesophageal clefts (LTEC) are uncommon congenital anomalies that
      occur when the primitive foregut fails to separate into the esophagus and
      trachea. The surgical repair strategy involves separation or partition of the
      common tract. Reported here is the authors' experience with 2 cases of LTEC (type
      3) repaired with bilateral musculomucosal flaps through the anterior wall of the
      trachea.

PMID- 14666452
TI  - Fundal tube esophagoplasty for esophageal reconstruction in atresia.
AB  - PURPOSE: This is a report of 4 patients with long gap/pure esophageal atresia,
      who, after an initial gastrostomy and cervical esophagostomy at birth, were
      treated with a new technique called fundal tube esophagoplasty. METHODS: The
      technique consisted of mobilization of the distal esophageal stump, division of
      the left gastric artery, and mobilization of upper half of stomach. Both walls of
      the stomach were incised in the region of the fundus starting on the lesser
      curvature in such a way that a tube was created out of the fundus, and the native
      esophageal stump appears to be an extension of this neoesophagus. This
      neoesophagus was brought to the neck by the retrosternal route and in a second
      stage, esophago-esophageal anastomosis was made. Thal's fundoplication was added
      in 2 cases. RESULTS: All the stages have been completed successfully in 4 babies.
      They have been followed up for periods ranging from 8 to 24 months after
      restoration of esophageal continuity. All the children are thriving. CONCLUSIONS:
      Fundal tube esophagoplasty (1) serves to provide a neoesophagus of natural
      caliber, (2) utilizes native esophagus in reconstruction, (3) does not produce a
      space-occupying problem in the mediastinum, and (4) preserves the gastric
      reservoir function. In this early experience, it appears to fulfill all the
      requirements of a good esophageal substitute.

PMID- 14666453
TI  - Outcomes in esophageal atresia and tracheoesophageal fistula.
AB  - BACKGROUND/PURPOSE: The purpose of this analysis was to investigate outcomes in
      newborns with esophageal atresia (EA) or tracheoesophageal fistula (TEF) with
      respect to prognostic classifications and complications. METHODS: Charts of all
      144 infants with EA/TEF treated at British Columbia Children's Hospital (BCCH)
      from 1984 to 2000 were reviewed. Patient demographics, frequency of associated
      anomalies, and details of management and outcomes were examined. RESULTS:
      Applying the Waterston prognostic classification to our patient population,
      survival rate was 100% for class A, 100% for class B, and 80% for class C. The
      Montreal classification survival rate was 92% for class I and 71% for class II (P
      =.08). Using the Spitz classification, survival rate was 99% for type I, 84% for
      type II, and 43% for type III (P <.05). The Bremen classification survival rate
      was 95% "without complications" and 71% "with complications." Complications
      included stricture (52%), gastroesophageal reflux (31%), anastomotic leakage
      (8%), recurrent fistula (8%), and pneumonia (6%). Seventeen patients underwent
      fundoplication for gastroesophageal reflux, 16 pre-1992 and one post-1992.
      CONCLUSIONS: Comparing the major prognostic classifications, the Spitz
      classification scheme was found to be most applicable. In our institution, the
      trend in management of gastroesophageal reflux after repair of EA/TEF has moved
      away from fundoplication toward medical management.

PMID- 14666454
TI  - Differential gene expression profiles between neuroblastomas with high telomerase
      activity and low telomerase activity.
AB  - PURPOSE: Neuroblastoma shows remarkable heterogeneity, resulting in favorable or
      unfavorable outcomes. The authors previously reported that high levels of
      telomerase activity correlated with unfavorable tumors, and telomere shortening
      without telomerase activity correlated with tumor regression. To identify the
      genes responsible for the biological characteristics of neuroblastoma, the
      authors applied microarray techniques. METHODS: Mixtures of total RNAs extracted
      from 10 neuroblastoma tissues with high and 10 with low telomerase activity were
      labeled with Cy3 or Cy5 by reverse transcriptase reaction, respectively, and
      hybridized with our original microarrays prepared with a cDNA library of human
      fetal brain. RESULTS: Expression of 63 genes including MYCN, hTERT, HSPCA, and
      cell cycle-related proteins was found to be increased in neuroblastomas with high
      telomerase activity, whereas another 46 genes, including neural differentiating
      genes, were detected as highly expressed in tumors with low telomerase activity.
      CONCLUSIONS: The expression profiling data indicated clusters of upregulated and
      downregulated genes tumors with high or low telomerase activity. The genes
      involved in differentiation/growth arrest of tumor cells were closely related to
      low telomerase activity in neuroblastoma. The genes overexpressed in tumors with
      high telomerase activity, including cell-cycle-related genes and transcriptional
      factors, would be candidates for novel prognosis-predicting factors as well as
      new therapeutic targets in aggressive neuroblastomas.

PMID- 14666455
TI  - Clinical significance of intensive surgery with intraoperative radiation for
      advanced neuroblastoma: does it really make sense?
AB  - PURPOSE: The aim of this study was to evaluate the significance of intensive
      surgery combined with intraoperative radiation therapy (IORT) in advanced
      neuroblastoma. METHODS: Clinical features and outcome were reviewed in 33
      advanced neuroblastoma patients (24 with INSS stage 4, 9 with stage 3), who had
      surgery (total excision 29, subtotal excision 4) with IORT (10 to 15 Gy) against
      the primary tumor site. RESULTS: Three patients (8.8%) had relapse at the primary
      site, all of which arose from the unirradiated area after stem cell
      transplantation. Among 29 patients with total excision, disease-free survival was
      obtained in 15 (51.7%) for an average of 6.9 years, which included 5 survivors of
      9 patients (55.9%) with amplified N-myc. In contrast, none of 4 patients with
      macroscopic residual survived. The Kaplan-Meier analysis showed significantly
      longer survival rates in the patients with total resection compared with those
      with macroscopic remnants. CONCLUSIONS: The intensive surgery with IORT
      dramatically increased the local eradication and improved the outcome even in
      advanced neuroblastoma with N-myc amplification. However, long-term survival was
      not obtained in patients with unresectable residual disease. These results may
      indicate the key role of surgical eradication in advanced neuroblastoma.

PMID- 14666456
TI  - Critical analysis of clinical research reporting in pediatric surgery: justifying
      the need for a new standard.
AB  - BACKGROUND/PURPOSE: Clinical practice in surgery relies heavily on observational
      data in which accurate and nonbiased reporting is critical. This study aims to
      assess the adequacy of clinical research reporting in pediatric surgery and to
      develop a means to raise the standard of such reporting. METHODS: The authors
      analyzed all observational studies published in The Journal of Pediatric Surgery
      from 1997 to 2002 (n = 300). Studies were assessed for 16 baseline criteria
      essential for the nonbiased reporting of clinical data (details regarding
      surgeons, cases, interventions, and statistical methods). Seven additional
      criteria pertaining to comparison methods were assessed in studies using
      controls. RESULTS: Ninety-five percent of all studies were retrospective, and
      only 25% utilized a control group. Most studies met less than half of the
      essential reporting criteria (mean, 7.6 of 16 baseline criteria; 3.3 of 7
      comparison criteria). Reporting deficiencies were found in all major aspects of
      study design and statistical analysis. CONCLUSIONS: More rigorous reporting of
      clinical data in pediatric surgery could increase the clinical utility of
      published results. The authors have identified the fundamental elements essential
      to nonbiased reporting of clinical research data in surgery. Implementation of
      mandatory peer-review guidelines based on these principles could set a new
      standard for clinical reporting in surgery.

PMID- 14666457
TI  - Introduction of an all-electronic administrative process for a major
      international pediatric surgical meeting.
AB  - BACKGROUND/PURPOSE: The administrative process for annual meetings is time
      consuming and increasingly costly when accomplished by traditional postal, fax,
      and telephone methods. The Pacific Association of Pediatric Surgeons introduced
      an all-electronic communication format for its 2002 annual meeting. Attendee
      acceptance and administrative and financial impact were evaluated. METHODS:
      Interested physicians were directed to a Website containing detailed information
      and electronic forms. E-mail was used for the abstract selection and manuscript
      submission processes. Attendees were surveyed to evaluate the new format.
      Administrative costs for the new format were compared with estimated costs for a
      comparable traditionally managed meeting. RESULTS: Attendance was similar to that
      at previous US meetings. Eighty-two percent of respondents approved of the all
      electronic format, although 48% believed a choice should remain. None suggested a
      complete return to the traditional format. Abstract and manuscript processing
      time was reduced substantially as were administrative costs (79.43 dollars
      savings per physician registrant). CONCLUSIONS: Adoption of an all-electronic
      annual meeting administrative process was associated with substantial cost
      reduction, increased efficiency, and excellent attendee satisfaction. This
      technology can help avoid increased registration fees while easing the burden on
      physician volunteers.

PMID- 14666458
TI  - The split abdominal wall muscle flap--a simple, mesh-free approach to repair
      large diaphragmatic hernia.
AB  - PURPOSE: The authors present a technique to repair large diaphragmatic hernias
      that is simple, can be done primarily, and offers a durable closure with living
      tissue. METHODS: A review of congenital diaphragmatic hernias was performed for
      the period between January 1991 and August 2000. Repair types included primary
      repair, synthetic patch, or a split abdominal wall muscle flap. The split
      abdominal wall muscle flap is performed by downward rotation of the internal
      oblique and transversalis abdominal wall muscles. This repair requires that the
      initial subcostal incision be positioned at least 4 to 5 cm below the costal
      margin, low enough to insure an adequate length of muscle will be available to
      fill the defect. RESULTS: Eight of 158 children with congenital diaphragmatic
      hernia underwent repair by abdominal wall muscle flap. Five of 8 had complete
      agenesis. Five survived the newborn period. Of the survivors, 4 of 5 required an
      additional surgical procedure, but none have had a recurrent hernia. CONCLUSIONS:
      The split abdominal wall muscle flap is an effective technique to close large
      diaphragmatic hernias. The repair was carried out successfully in 8 patients with
      massive defects. In the surviving patients, the repair has proven to be a durable
      restoration of the diaphragm.

PMID- 14666459
TI  - Body wall repair using small intestinal submucosa seeded with cells.
AB  - BACKGROUND/PURPOSE: Prosthetic repair of large ventral abdominal wall defects has
      been associated with high complication rates. This study was aimed at applying
      tissue engineering to body wall replacement. METHODS: Syngeneic Lewis rats
      underwent harvest of skeletal muscle specimens. Once expanded in vitro, skeletal
      muscle cells or fibroblasts were suspended in a collagen gel. All animals
      underwent creation of a 2.5- x 3-cm abdominal wall defect. The defect was
      repaired with the cell-seeded gel placed in between 2 pieces of small intestinal
      submucosa (SIS). The control group was repaired by SIS with acellular gel.
      Animals were killed at different time-points for histologic and mechanical
      examination. Statistical analysis was by analysis of variance (ANOVA). RESULTS:
      Abdominal wall hernia was present in 6 of 24 fibroblast-seeded constructs (25%),
      5 of 21 skeletal muscle cell-seeded constructs (23.9%), and 16 of 21 acellular
      grafts (76.2%), respectively (P <.05). At harvest, cell-seeded constructs were
      thicker with better cellular infiltration, whereas acellular grafts were thin,
      low in cell density, and poor in mechanical resistance. CONCLUSIONS: Unlike
      acellular collagen matrices, engineered cellular constructs have better cell
      infiltration and mechanical performance. Tissue engineering may be a viable
      alternative for body-wall replacement.

PMID- 14666460
TI  - Single umbilical artery and the VATER-animal model.
AB  - BACKGROUND/PURPOSE: Vascular disruption is recognized as a cause of congenital
      malformations. The authors analyzed the significance of single umbilical artery
      (SUA) in the Adriamycin-animal model to find out if it was associated with organ
      malformations. METHODS: Pregnant SD rats were injected with Adriamycin
      intraperitoneally at a dose of 2 mg/kg on days 6 through 9 of gestation. Serial
      transverse sections of full-term fetuses were analyzed by light microscopy.
      Embryos also were removed on different gestational days during organogenesis, and
      serial transverse histologic sections were examined and compared with suitable
      controls. RESULTS: In experimental embryos (n = 47), presence of a SUA resulted
      from either persistence of the primitive umbilical arteries that joined each
      other ventral to the hind gut to give rise to one umbilical artery or from
      secondary atrophy of one of the definitive umbilical arteries. Malformations such
      as intestinal atresia were associated with anomalous fusion between the dorsal
      aorta and the persistent primitive umbilical arteries. CONCLUSIONS: SUA is a
      prominent feature of the Adriamycin-animal model. No obvious association was
      found between malformations and SUA that resulted from atrophy of one of the
      definitive umbilical arteries; however, it was associated with anomalies such as
      intestinal atresia when it resulted from persistence of the primitive umbilical
      arteries.

PMID- 14666461
TI  - Long-term efficacy of partial splenic embolization in children.
AB  - PURPOSE: To elucidate the role of partial splenic embolization (PSE) procedures,
      long-term outcome was assessed in terms of the recurrence of thrombocytopenia.
      METHODS: A retrospective study was performed after 41 PSE procedures in 36
      patients for hypersplenism owing to portal hypertension. The underlying disease
      was biliary atresia in 32 patients, extrahepatic portal obstruction in 3, and
      idiopathic cirrhosis in 1. RESULTS: The average volume embolized was 70.1%. The
      patients were followed up from 20 days to 182 months (average, 70.8 months). Five
      patients subsequently died, and 6 underwent liver transplantation. The causes of
      death or the reasons for liver transplantation were not related to hypersplenism.
      Eleven patients (30.6%) had recurrence of thrombocytopenia (<100,000/mm3). There
      was no significant difference in the volume embolized or platelet count before
      PSE between the patients with and without recurrence of thrombocytopenia. The
      peak value of platelet count after PSE was significantly lower in the patients
      with recurrence of thrombocytopenia (P =.0091). In 17 of 24 survivors without
      liver transplantation, platelet counts remained normal throughout the follow-up
      period. CONCLUSIONS: PSE is a safe and effective procedure. Hematologic indices
      improved in all 36 patients after PSE, and its long-term efficacy was shown in
      70% of the survivors.

PMID- 14666462
TI  - Living-related bowel transplantation to treat short bowel syndrome in a four-year
      old child: a case report.
AB  - PURPOSE: Short bowel syndrome (SBS) is an extremely challenging clinical problem
      in children. Although many patients can be maintained for a period of time on
      total parenteral nutrition (TPN), many of these children suffer from the
      morbidity and mortality associated with sequential central line infections,
      venous thromboses, and TPN-induced liver failure. Intestinal transplantation
      often is the only chance for long-term survival. Unfortunately, many children die
      every year waiting for size-matched cadaveric intestine to become available.
      METHODS: After our success with living-related bowel transplantation in adults,
      the authors successfully transplanted 150 cm of maternal ileum into a 4-year-old
      10-kg child with profound malnutrition from SBS and advanced TPN-induced liver
      failure. Because of the size mismatch, the abdominal cavity could not be closed
      primarily. The defect was covered with absorbable mesh and subsequently with skin
      graft. RESULTS: The patient is home with excellent bowel and liver function, off
      hyperalimentation, and on a regular diet. No rejection has been encountered.
      CONCLUSIONS: Living-related intestinal transplantation is a life-saving
      alternative to cadaveric intestinal transplantation in children with short bowel
      syndrome.

PMID- 14666463
TI  - Does transitional zone pull-through in Hirschsprung's disease imply a poor
      prognosis?
AB  - PURPOSE: Accurate frozen section interpretation of intraoperative biopsies is
      critical to the success of the Duhamel procedure. Errors during sampling or
      interpretation may result in an abnormal pull-through. The authors' aim was to
      determine the incidence and outcome of transitional zone pull-through (TZPT).
      METHODS: Ninety-six children who underwent a Duhamel procedure between January
      1987 and May 2002 were followed up prospectively. The outcome of 18 children with
      TZPT was compared statistically with that of a cohort of 58 patients with a
      ganglionic pull-through. RESULTS: The incidence of TZPT was 18.8%. Concordance
      rate between frozen and paraffin-section analyses was 88.5%. The incidence of
      enterocolitis (P =.003) and intractable constipation (P =.02) was found to be
      significantly higher in TZPT. There was no significant difference in continence
      (P =.34), rectal sensation (P =.35), and control (P =.53). Five (27.8%) TZPT
      patients required a revisional surgery for failure of conservative management.
      The incidence of stoma placement and revision was significantly less in the
      ganglionic group (3.4%, P =.007). CONCLUSIONS: Up to one third of patients with
      TZPT will require revisional surgery for intractable symptoms. Vigilance is
      warranted in view of the greater risk of enterocolitis. Continence is not
      significantly affected.

PMID- 14666464
TI  - Laparoscopically assisted anorectovaginoplasty for selected types of female
      anorectal malformations.
AB  - PURPOSE: The aim of this study was to describe laparoscopically assisted
      anorectovaginoplasty (LAARVP) for the repair of selected types of female
      anorectal malformation. METHODS: Five cases (case 1, rectovaginal fistula with a
      high rectum; case 2, rectovestibular fistula with double vagina; case 3,
      rectovestibular fistula with absent vagina; case 4, anovestibular fistula with
      absent vagina; case 5, cloaca) were reviewed. RESULTS: Patient 4 had undergone a
      posterior sagittal anorectoplasty without vaginoplasty at another hospital after
      misdiagnosis of simple anovestibular fistula. Mean age at LAARVP was 15.4 months.
      At LAARVP, the fistula was divided in cases 1 through 4 and dissected as low as
      possible in case 5. In cases 3 and 4, the distal fistula was used to create the
      neovagina. In cases 1 through 3, the proximal rectum was mobilized and brought
      through the pelvic floor sphincter muscles using Georgeson's laparoscopically
      assisted colon pull-through technique through a minimal perineal incision. A
      posterior sagittal incision was required in cases 4 and 5. However, the initial
      laparoscopic approach was very helpful in both cases. Currently, all patients are
      well after a mean follow-up period of 32.2 months. Mean current age is 4.0 years.
      Patients 1 through 3 are continent, patient 4 is incontinent with soiling, and
      patient 5 is too young to be evaluated. CONCLUSIONS: LAARVP helps to achieve low
      dissection of the fistula, gives optimal view of the pelvic organs, provides
      accurate placement of the anorectal pull-through, and minimizes abdominal
      perineal scars.

PMID- 14666465
TI  - Endorectal pull-through with posterior sagittal approach to the repair of
      postoperative rectourethral and rectovaginal fistula.
AB  - BACKGROUND/PURPOSE: Rectourethral (RUF) or rectovaginal fistula (RVF) is a
      troublesome complication after anorectal surgery because of dense adhesions
      around the fistula. The authors applied a new technique for the redo surgery.
      METHODS: Case 1 is Hirschsprung's disease in a 1-year-old boy who underwent
      modified Duhamel's procedure and had RUF. Case 2 is rectovestibular fistula in an
      11-year-old girl who had anterior sagittal anorectoplasty complicated by RVF.
      Case 3 is multiple urogenital anomalies including rectovesical fistula in a 4
      year-old boy in whom transvesical repair was unsuccessful. The colon was
      mobilized as far as possible at laparotomy. The rectum was opened via a posterior
      sagittal approach leaving 1 cm of the anal canal. Extended endorectal mucosectomy
      was performed to the dentate line, and the fistula was closed from inside of the
      rectum. The remaining mucosal cuff was everted out of the anus and the intact
      colon was pulled through the rectum and anastomosed to the cuff extraanally.
      RESULTS: The postoperative contrast enema showed no recurrent fistula, and
      defecation was not impaired. CONCLUSIONS: Endorectal pull-through of the intact
      colon can spare troublesome mobilization of the fistula and can prevent the
      recurrence of fistula. Rectal incision via a posterior sagittal approach provides
      a direct view of the fistula.

PMID- 14666466
TI  - Left-colon antegrade continence enema (LACE) procedure for fecal incontinence.
AB  - PURPOSE: Antegrade continence enemas (ACE) are an efficacious therapeutic option
      for patients with fecal incontinence. The authors review their institution's
      experience with a variation of the Monti-Malone ACE procedure using the left
      colon as a source of an intestinal conduit and enema reservoir. METHODS: From
      2000 to 2002, 18 patients with fecal incontinence or intractable constipation
      underwent left-colon ACE (LACE) procedure. Concomitant Mitrofanoff
      appendicovesicostomy was performed in 15 patients and bladder augmentation in 9.
      The majority of patients had neural tube defects. A segment of left colon was
      tubularized, tunneled into the muscular wall of the distal colon, and
      exteriorized through the left upper quadrant or midabdomen. Stomal catherization
      and enema installation were started one month postoperatively. RESULTS: Fifteen
      patients (83%) achieved fecal continence, 2 remain incontinent of stool, and 1
      experienced stomal closure (mean follow-up was 24 +/- 9 months). Two patients had
      stomal stenosis that required revision. The mean enema volume in patient's
      achieving continence was 360 +/- 216 mL, and the mean transit time was 18 +/- 12
      minutes. CONCLUSIONS: LACE is an efficacious procedure for fecal incontinence
      that can be performed safely at the time of major urologic reconstruction.
      Administration of enemas into the left colon has several physiologic advantages
      that result in predictable bowel evacuation.

PMID- 14666467
TI  - Tissue-engineered urinary bladder wall using PLGA mesh-collagen hybrid scaffolds:
      a comparison study of collagen sponge and gel as a scaffold.
AB  - PURPOSE: Tissue engineering of the urinary bladder using autologous cells and
      biodegradable scaffold is a promising method for augmentation. The authors
      developed 2 hybrid scaffolds by combining poly (DL-lactic-co-glycolic acid; PLGA)
      mesh for mechanical strength with collagen sponge or gel suitable for cell
      seeding. The aim of this study was to compare collagen as a scaffold between
      collagen sponge and gel and to construct a tissue-engineered urinary bladder wall
      utilizing these hybrid scaffolds. METHODS: The PLGA mesh-collagen hybrid
      scaffolds were prepared by introducing collagen sponge or gel into the PLGA
      knitted mesh. Urothelial and smooth muscle cells were obtained from porcine
      urinary bladder wall and were cultured in their respective media. The cells were
      seeded on these hybrid scaffolds. These constructs were analyzed morphologically
      and immunohistochemically. RESULTS: The urothelial layer was generated 3
      dimensionally by culturing urothelial cells with PLGA mesh and collagen sponge.
      The smooth muscle layer was constructed by culturing smooth muscle cells with
      PLGA mesh and collagen gel. And a novel tissue-engineered urinary bladder wall
      was constructed laminating the urothelial and smooth muscle layers. CONCLUSIONS:
      Ex vivo construction of urinary bladder wall using hybrid scaffolds prepared by
      combining PLGA mesh with collagen sponge or gel was successful. This tissue
      engineered urinary bladder wall allows easy handling and may become a promising
      tool for bladder augmentation.

PMID- 14666468
TI  - Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb.
AB  - PURPOSE: It was still unclear how urinary tract obstruction alters normal
      nephrogenesis and leads to renal dysplasia. The authors created an obstructive
      uropathy model in fetal lambs and reviewed the pathology of the obstructed kidney
      to determine the optimal timing for decompression of the obstruction. METHODS:
      Obstructive uropathy was created in fetal lambs at 60 days' gestation by ligating
      the urethra and urachus. They were delivered 20 to 31 days later by cesarian
      section. The kidneys were processed for histologic examination. RESULTS: Thirty
      four 60-day lambs were operated on. Dysplastic changes were noted in 25 fetuses,
      and 24 fetuses had cysts in the nephrogenic zone. The cystic components in
      multicystic dysplastic kidneys (MCDK) are mainly in the proximal tubules.
      CONCLUSIONS: In utero urinary tract obstruction causes reduction of numbers of
      functioning nephrons and produces cysts in the nephrogenic zone and in the deeper
      cortex. These cysts and dilated proximal tubules suppress new nephron formation.
      Twenty days after obstruction, there were early features of dysplasia, but the
      nephrogenic zones still were present. Early shunting may salvage renal function.

PMID- 14666469
TI  - Guide wire-assisted urethral dilatation for urethral strictures in pediatric
      urology.
AB  - PURPOSE: The aim of this study was to report the results of 32 cases of
      dilatation of urethral stricture using a guide wire and sheath dilator technique
      supplemented by clean intermittent catheterization if further stabilization of
      the urethral stricture was felt warranted. METHODS: The procedure involves
      insertion of a straight flexi-tip lubricated guide wire through the urethral
      stricture under cystoscopic guidance followed by insertion of a series of sheath
      dilators. Dilatation was followed by insertion of a Foley catheter, which was
      left in situ for 1 to 3 days. Patients underwent repeat cystoscopy to evaluate
      the urethra for recurrent stricture and those with a recalcitrant stricture were
      commenced on clean intermittent catheterization (CIC) to stabilize the narrowing.
      RESULTS: Thirty-two patients were included. They have been followed up for up to
      2(1/2) years after their last cystoscopy (mean, 16 months). Thirteen of 32
      patients had more than 4 dilatations under anesthesia. Twelve patients had
      undergone CIC postoperatively. Complications included a urinary tract infection
      in 3 boys and bladder spasms in one. No false passage or sepsis occurred with
      this approach. CONCLUSIONS: Guide wire-assisted urethral dilatation helps avoid
      risks associated with blind dilatation techniques and appears to be a safe and
      simple alternative for management of urethral strictures in pediatric urology.

PMID- 14666470
TI  - Transabdominal testicular descent is disrupted in mice with deletion of
      insulinlike factor 3 receptor.
AB  - BACKGROUND: Several factors are implicated in transabdominal testicular descent,
      including insulinlike factor 3 (INSL3) hormone and Mullerian-inhibiting substance
      (MIS). A transgene insertional mutation found on chromosome 5 in the mouse, known
      as crsp, causes deletion of a transmembrane G protein-coupled receptor gene,
      Great, which is highly expressed in the gubernaculum. The authors describe here a
      detailed analysis of the testicular descent and gubernacular development in crsp
      mice to determine the role of the Great gene in this process. METHODS: Homozygous
      (crsp/crsp) mutant and wild-type heterozygous (crsp/+) mice were examined at
      birth (D 0) and at days 10 (D 10) and 30 (D 30) postnatally. Serial sagittal or
      coronal sections were analyzed for position of the gonads and cremaster sac
      development. RESULTS: Transabdominal testicular descent was absent at D 0 in
      crsp/crsp homozygous mice with no swelling reaction in the gubernacula. By D 10
      the cremaster sac was significantly thinner (P <.05) and contained less collagen
      in the mutants than in the wild-type controls. On D 30 the cremaster sacs of
      mutant males were similar in thickness to those in females. CONCLUSIONS:
      Disruption of the Great gene causes failure of the transabdominal phase of
      descent, identical to that seen in the Insl3-deficient mutants, consistent with
      the recent data suggesting that Great gene encodes the Insl3 transmembrane
      receptor. No differences between D 30 mutant males and females were found in the
      gubernacula, suggesting that Insl3/Great signaling regulates gubernacular
      development.

PMID- 14666471
TI  - A novel technique for reinforcing the neourethra in hypospadias associated with
      bilateral undescended testis: use of the gubernaculum.
AB  - The authors present 3 cases of proximal hypospadias associated with bilateral
      undescended testes (UDT) in which the gubernaculum was used to reinforce the
      neourethra to prevent urethrocutaneous fistula. This is the first report of the
      gubernaculum being used to reinforce the neourethra. The technique is simple and
      should be applicable to any hypospadias patient with concomitant UDT, especially
      in severe hypospadias. Good outcome is likely because of the excellent blood
      supply of the gubernaculum.

PMID- 14666472
TI  - Experimental allogenic penile transplantation.
AB  - PURPOSE: The aim of this study was to assess the feasibility of allogenic penile
      transplantation (PTx) for creating a source of viable penile tissue for use in
      penile reconstruction. METHODS: The entire penis from an adult Brown-Norway rat
      was transplanted into a pouch created in the omentum of an adult Lewis rat (fully
      allogenic PTx, n = 23). Recipients were divided into 2 groups according to
      immunosuppressant (FK506) usage: in the FK+ group, FK506 (0.6 mg/kg/d) was
      administered intraperitoneally until a predetermined day (day 3, 5, 7, 10, 14, or
      21) after PTx, and then the grafts were harvested. No FK506 was used in the FK-
      group. Syngeneic PTx (n = 8) patients were used as controls. All grafts were
      stained with H&E for histologic examination. RESULTS: At laparotomy, each
      successfully transplanted penis appeared as a cylindrical mass in the omentum.
      Grafts could be mobilized to the genital area because of a long omental pedicle.
      Graft survival in the control and FK+ groups was 100%. Rejection was minimal to
      moderate in FK+ grafts harvested on days 3 and 5 after PTx and minimal or absent
      in FK+ grafts harvested on days 7, 10, 14, and 21. Penile structure on H&E
      staining was normal in FK+ and control specimens. Rejection with massive cellular
      infiltration was observed in all FK- grafts. CONCLUSIONS: FK506 successfully
      prevented rejection in allogenic PTx, and the authors' technique has potential
      for creating viable penile tissue that could be used as an option for penile
      reconstruction.

PMID- 14666473
TI  - A role of cytokines in OK-432 injection therapy for cystic lymphangioma: an
      approach to the mechanism.
AB  - PURPOSE: This study examines cytokine levels of aspirates from cystic
      lymphangiomas after injection of OK-432 and over the course of several weeks to
      better understand the process of tumor regression. METHODS: Fluids aspirated from
      lymphangioma cysts of 3 patients were collected sequentially before and after OK
      432 injection. Mononuclear cells (MNCs) were separated and cultured with or
      without OK-432. Vascular endothelial growth factor (VEGF), soluble VEGF receptor
      1 (sVEGFR1), sVEGFR2, transforming growth factor beta-1 (TGF-beta1), interleukin
      (IL)-6, IL-8, IL-12+p40, tumor necrosis factor alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) levels in the supernatants of the aspirates and the culture
      supernatants of MNCs were then measured by ELISA. RESULTS: The aspirates
      exhibited a marked elevation in IL-6, IL-8, VEGF, and TGF-beta1 levels for a few
      weeks after the OK-432 injection. IL-6, IL-8, IL-12+p40, TNF-alpha, and IFN-gamma
      levels were elevated in the culture supernatants of the MNC cultured with OK-432
      for up to 9 days. All the tumors regressed significantly, with sclerotic change,
      within 3 months after OK-432 injection. CONCLUSIONS: Cytokine production is
      maintained for a few weeks after OK-432 injection. Fibrotic changes may be
      another main mechanism in tumor regression in addition to cytotoxic effects on
      lymphangioma cells. A close relationship between cytokines from intracystic cells
      and lymphangioma cells is suggested.

PMID- 14666474
TI  - Enteric duplications presenting as antenatally detected abdominal cysts: is
      delayed resection appropriate?
AB  - PURPOSE: The aim of this study was to evaluate delayed elective resection of
      antenatally detected enteric duplication cysts. METHODS: A retrospective casenote
      study of intraabdominal cysts detected antenatally between January 1991 and
      January 2002 found 37 fetuses with cysts. Twelve were enteric duplications. Two
      were duodenal, 1 was an 85-cm tubular jejunoileal duplication, and 9 were
      ileocecal. Asymptomatic cysts were followed with serial ultrasound scars and
      resected electively over 14 months. RESULTS: Three neonates had small bowel
      obstruction demanding laparotomy: 1 of the 2 infants with duodenal duplication
      cysts, 1 infant with an ileocecal duplication, and the infant with the tubular
      duplication. One with an ileocecal duplication became symptomatic at 2 months and
      underwent a laparotomy. Seven had their duplications resected electively between
      6 weeks and 14 months, and the other is still being followed. Four of the 7
      asymptomatic duplications electively resected contained gastric mucosa.
      CONCLUSIONS: Intraabdominal enteric duplication cysts are increasingly likely to
      be detected antenatally. The majority are likely to remain asymptomatic for
      several months at least, after which a resection can be planned. The prevalence
      of gastric mucosa suggests that they should not be left indefinitely.
      Laparoscopically assisted resection of ileocecal duplications is safe and
      effective.

PMID- 14666475
TI  - Peritoneal drainage as definitive management of intestinal perforation in
      extremely low-birth-weight infants.
AB  - BACKGROUND/PURPOSE: The optimal management of extremely low-birth-weight (ELBW)
      infants with intestinal perforation remains unclear. The authors evaluated ELBW
      neonates with intestinal perforation in whom peritoneal drainage (PD) was
      intended as definitive therapy. METHODS: The records of 29 consecutive ELBW
      infants with intestinal perforation were reviewed. All underwent PD. Survival,
      the need for other abdominal procedures, the transition to enteral feeding, and
      the incidence of cholestasis and infectious complications were noted. Variables
      associated with nonsurvival were assessed. RESULTS: Overall survival rate was
      66%. In 24% of cases, a second abdominal procedure was required. Full feedings
      were achieved at a mean of 69 days. Extraabdominal infectious complications
      occurred in 63% of survivors, and direct bilirubin was greater than 2.0 mg/dL in
      57% at 2 months. Thrombocytopenia and vasopressor requirements at the time of
      perforation were associated with nonsurvival. CONCLUSIONS: In this consecutive
      series of ELBW infants in whom PD was intended as definitive treatment for
      intestinal perforation survival was comparable with that found in series in which
      immediate laparotomy and resection were used. Few secondary abdominal procedures
      were required. The interval between PD and full enteral nutrition, however, was
      long, and the incidence of nonabdominal infectious complications and cholestasis
      was substantial.

PMID- 14666476
TI  - Clinical features and treatment outcome of intussusception in premature neonates.
AB  - BACKGROUND/PURPOSE: Less than 1.3% of all cases of intussusception occur in term
      neonates. Intussusception in premature neonates (IPN) is exceedingly rare. Its
      rarity and difficulty to differentiate IPN from common neonatal diseases like
      necrotizing enterocolitis (NEC) often delays its diagnosis. The authors set out
      to characterize diagnosis, treatment, and outcome of this rare condition.
      METHODS: The authors analyzed 2 new cases of IPN and 33 previously reported cases
      from the literature. RESULTS: The 35 patients with IPN had an average gestational
      age, postconceptual age at diagnosis, and birth weight of 28.4 +/- 0.6 weeks (all
      data, mean +/- SEM), 31.1 +/- 0.5 weeks, and 1,165 +/- 21 g, respectively.
      Gastrointestinal symptoms first presented at age 8 +/- 1 days. A preoperative
      diagnosis of NEC was assumed in 24 patients, delaying diagnosis by 10 +/- 2 days.
      Intussusception was diagnosed radiographically in 2 patients (1 contrast enema
      and 1 ultrasound scan) and during surgery or autopsy in the remainder. Resection
      was reported in 28 patients for bowel that was irreducible, necrotic, or
      perforated. The overall mortality rate was 20%, mainly owing to sepsis.
      CONCLUSIONS: Intussusception in the premature neonate often is misdiagnosed as
      NEC, delaying operative intervention. Contrast enema has limited diagnostic
      capability. Early diagnosis may be achieved with use of ultrasound scan.
      Intussusception can be treated successfully with resection and primary
      anastomosis, achieving good results.

PMID- 14666477
TI  - Uptime as a measure of recovery in children postappendectomy.
AB  - PURPOSE: The aim of this study was to objectively measure recovery time after
      open and laparoscopic appendectomy using an activity monitor (PAL 1). METHODS:
      The PAL 1 records the amount of time that the subject is upright (uptime).
      Children wore the PAL 1 for 10 days continuously, beginning within the first 48
      hours postoperatively. RESULTS: Uptime data were collected for 5 or more days for
      42 children (open, n = 16; laparoscopic, n = 26). All children had low levels of
      uptime in the initial postoperative period. There was weak evidence of a quicker
      recovery rate for children in the laparoscopic group (P =.09). The difference in
      mean uptime between groups was of statistical significance by day 7
      postoperatively with children in the laparoscopic group having a higher mean
      uptime than those in the open group (difference of 0.7 hours; 95% confidence
      intervals 0.0 to 1.4 hours in a 24-hour period). CONCLUSIONS: The results of this
      study show that recovery postappendectomy can be quantified by the measurement of
      uptime and that children undergoing a laparoscopic procedure may recover
      marginally more quickly than those undergoing an open procedure.

PMID- 14666478
TI  - The intussusception antireflux valve is ineffective for preventing cholangitis in
      biliary atresia: a prospective study.
AB  - PURPOSE: Cholangitis after Kasai portoenterostomy for biliary atresia (BA)
      strongly influences outcome, and an intussusception antireflux valve (IAV) in the
      Roux-en-Y limb has been advocated for the prevention of cholangitis without
      definitive evidence. The authors report a prospective study to evaluate the
      effectiveness of IAV in BA. METHODS: Twenty-one consecutive patients with
      uncorrectable-type BA were the subjects for this study. IAV was included based on
      informed parental request to give 2 groups: IAV- (n = 11) and IAV+ (n = 10). The
      incidence/duration of episodes of cholangitis (temperature > 38 degrees C,
      elevated serum bilirubin level, and leukocytosis) during the first 6 months after
      Kasai were statistically compared between the 2 groups (P >.05 was regarded as
      not significant). RESULTS: Technical variations in surgical technique were
      minimized because the same surgeon supervised all procedures. There were no
      significant differences between the 2 groups for age and weight at the time of
      Kasai, mean size of bile ductules at the porta hepatis, and degree of liver
      cirrhosis present. Protocols for antibiotic and steroid therapy were the same for
      both groups. The total number of patients who had cholangitis in the IAV- group
      was 6 of 11 and 5 of 10 in the IAV+ group (P = NS). The total number of episodes
      of cholangitis was 16 in the IAV- group versus 17 in the IAV+ group (P value, not
      significant). The mean duration of an episode of cholangitis (number of days per
      number of episodes) was 12 +/- 6 days in the IAV- group versus 11 +/- 7 days in
      the IAV+ group (P value, not significant). CONCLUSIONS: IAV does not make any
      significant impact on the incidence or duration of cholangitis in the early post
      Kasai period.

PMID- 14666479
TI  - Recommendations for preventing complications related to Roux-en-Y hepatico
      jejunostomy performed during excision of choledochal cyst in children.
AB  - PURPOSE: The aim of this study was to review the outcome of a protocol the
      authors proposed for preventing Roux-en-Y hepatico-jejunostomy (RYHJ) related
      complications. METHODS: In 1986 the authors adopted the following protocol for
      improving RYHJ to minimize risks for RY-related complications: (1) end-to-end
      anastomosis if possible; (2) if end-to-side anastomosis is unavoidable, the
      common hepatic duct should be anastomosed as close as possible to the closed end
      of the blind pouch (BP); (3) careful selection of the vascular supply to the RY
      jejunal limb; (4) length of the RY jejunal limb should not be predetermined, but
      individualized; (5) approximate the native jejunum to the RY limb. The authors
      reviewed 92 children who had surgery for CC (mean age at surgery, 4.1 years) at
      our institution between 1986 and 2002 to assess the effectiveness of their
      recommendations. RESULTS: After the adoption of the authors' recommendations for
      RYHJ, they have experienced no RYHJ-related complications after a mean follow-up
      period of 7.6 years (range, 4 months to 16 years). CONCLUSIONS: RYHJ in children
      is different from that in adults, because the RY limb or BP can grow and elongate
      as the child grows. The authors' recommendations appear to have successfully
      prevented RY-related complications up to the time of this review, and they highly
      recommend their use.

PMID- 14666480
TI  - Forme fruste choledochal cyst: long-term follow-up with special reference to
      surgical technique.
AB  - PURPOSE: Forme fruste choledochal cyst (FFCC) is a choledochal cyst that has
      minimal or no dilatation of the extrahepatic bile duct (EHBD) and is associated
      with pancreaticobiliary malunion (PBMU). The authors reviewed the long-term
      outcome of their patients with FFCC. METHODS: Inpatient and outpatient records of
      281 patients with choledochal cyst were reviewed. In this study, minimal
      dilatation of the EHBD was defined as its maximum diameter being less than 10 mm.
      RESULTS: There were 17 cases of FFCC identified. In all 17 patients, PBMU was
      present. The mean age at EHBD excision was 2.9 years. Fourteen patients had
      hepatico-jejunostomy, and three had hepatico-duodenostomy. The histology of the
      excised EHBD showed mucosal ulceration/sloughing (in 35.3% patients), fibrosis
      (52.9%), and inflammatory cell infiltration (41.2%). Over a mean postoperative
      follow-up period of 9.8 years, there have been no episodes of cholangitis or
      anastomotic stricture formation. CONCLUSIONS: The treatment of choice for FFCC in
      children is EHBD excision and hepatico-jejunostomy. There is little surgical
      morbidity if performed carefully.

PMID- 14666481
TI  - The use of stab incisions for instrument access in laparoscopic operations.
AB  - BACKGROUND/PURPOSE: Traditional laparoscopic approaches require cannulas for
      instrument access to the abdominal cavity. This study reports the authors'
      experience using minimal access (MA) stab incisions, rather than cannulas, for
      insertion of laparoscopic instruments into the peritoneal cavity. METHODS: All
      patients undergoing MA procedures by the authors from November 1999 through March
      2003 were included. Procedures included foregut, biliary, adrenal, splenic,
      colonic, and genitourinary operations. A single cannula was used for insertion of
      the telescope. In select cases, a second cannula was needed for unique
      instruments (staplers/ultrasonic shears). Abdominal wall stab incisions (SI) were
      used for introduction of the remaining instruments. RESULTS: A total of 511 MA
      procedures were performed during the study period. Pneumoperitoneum was
      maintained in all cases. There were no complications associated with creation of
      the SI. A single-Step reposable (partially reusable, partially disposable)
      cannula and expandable sheath were used in 308 cases, whereas a second-Step
      reposable cannula and sheath were needed in 203 children. In total, 1,337
      cannulas were saved using this MA technique. The cost to the patient was 140
      dollars/Step cannula and sheath; overall cost savings were 187,180 dollars.
      CONCLUSIONS: MA procedures can be performed safely and effectively with a single
      or, occasionally, 2 cannulas. The cosmetic result is superior, and there are
      significant cost savings related to the elimination of accessory cannulas. The
      authors believe this technique of SI for instrument access is superior to the
      traditional cannula approach and can be utilized in most laparoscopic operations.

PMID- 14666482
TI  - James Warden, MD, and the GAP Program.

PMID- 14666485
TI  - Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure, and
      serial transverse enteroplasty for short bowel syndrome.

PMID- 14666486
TI  - The value of AFP in congenital cervical teratoma.

PMID- 14666492
TI  - Dietary guidelines: Past experience and new approaches. April 30-May 1, 2002,
      Toronto, Canada. Proceedings of a symposium.

PMID- 14666493
TI  - Evolution of dietary guidelines.
AB  - Advice on eating behavior, food choices, and food preparation have been
      incorporated into philosophical and religious writings over the ages; however, in
      the past 150 years, these recommendations have been based on science related to
      public health policy and medicine. In the first half of the 20th century, the
      focus was on sanitation and prevention of nutrient deficiency diseases. In the
      second half, the focus has shifted to prevention of chronic disease and dietary
      excesses that increase disease risk. Current guidelines recognize the importance
      of lifestyle as well as food and nutrition choices. Dietary guidelines that were
      developed in the early 1980s emphasized components of food such as saturated fat,
      individual nutrients, or fiber. Revisions of these guidelines have placed more
      emphasis on food choices rather than individual nutrients, and recommendations
      have become more food-based. The process developed by the Food and Agricultural
      Organization and World Health Organization for preparation and use of food-based
      dietary guidelines begins with analysis of the most critical public health issues
      that are related to diet and outlines strategies to identify food-based
      approaches to address these issues. Countries that have implemented this process
      indicate that consensus building accomplished through the process has allowed a
      multisector approaches for addressing diet-related public health problems.

PMID- 14666494
TI  - Setting dietary guidelines: the US process.
AB  - Nutrition and Your Health: Dietary Guidelines for Americans has been issued
      jointly by the US Departments of Health and Human Services (HHS) and Agriculture
      (USDA) every five years since 1980. The Dietary Guidelines form the cornerstone
      of federal nutrition policy and provide the basis for all federal nutrition
      education activities. Beginning with the 1985 edition, USDA and HHS have
      appointed a Dietary Guidelines Advisory Committee of prominent experts in
      nutrition and health to review recent advances in scientific and medical
      knowledge and to recommend revisions of the Dietary Guidelines, if warranted, to
      the Secretaries of HHS and USDA. The Committee's deliberations are informed by
      evidence-based reviews, consensus documents, peer-reviewed research studies, and
      by written and oral public comments. The Departments review the Committee's
      recommendations and rationale, make any necessary revisions, and jointly issue
      the final edition. Nutrition and Your Health: Dietary Guidelines for Americans is
      based on the best available science. Ultimately, its goal is to promote better
      health through food choices and physical activity. The Dietary Guidelines have
      been referred to as a "gold standard" of nutrition advice, amid often confusing
      messages about nutrition and health.

PMID- 14666495
TI  - Dietary guidelines: the development process in Australia and New Zealand.
AB  - There is increasing pressure on those developing public health guidelines such as
      the US Dietary Guidelines to take an evidence-based approach to review of the
      literature that is increasingly used for clinical practice guidelines. While the
      public health arena poses a number of problems in terms of the types of evidence
      available in many instances, one of the consequences of a move to an evidence
      based approach will be an increased demand on time and resources. Different
      countries have varying approaches to the development of dietary guidelines. This
      paper outlines the approaches used in Australia and New Zealand. It highlights
      the dependence on the goodwill of academics and other health professionals with
      limited capacity to undertake major, structured, evidence-based review of the
      extensive literature relevant to dietary guideline development. It further
      highlights the potential value of cross-country collaboration in establishing and
      maintaining a centralized, accessible evidence base for development or review of
      dietary guidelines.

PMID- 14666496
TI  - Setting dietary guidance: the Canadian experience.
AB  - This article outlines processes underlying recent dietary guidance in Canada. In
      1977, Nutrition Recommendations for Canadians were adapted from the Report of the
      Committee on Diet and Cardiovascular Disease. In the late 1980s, as science
      revealed new relationships between dietary patterns and chronic disease, the
      unified front of consistent dietary guidelines began to crumble when researchers
      and health organizations began to provide "unique" dietary advice. Evolution in
      health promotion concepts during this time, combined with the need for updated
      dietary guidance, influenced Health Canada to appoint two advisory committees in
      1987. The Scientific Review Committee was charged with describing the dietary
      pattern that would supply recommended levels of essential nutrients while
      reducing risk of chronic disease, resulting in updated Nutrition Recommendations.
      The Communications and Implementation Committee translated the scientific
      recommendations into dietary advice for the public, leading to Canada's
      Guidelines to Healthy Eating. From this process, Canada's Food Guide to Healthy
      Eating emerged. The development of the Dietary Reference Intakes has resulted in
      updated nutrient requirement values and better tools for dietary assessment and
      planning. Health Canada recognizes the need to ensure alignment with this updated
      science through continuing leadership in defining and communicating accurate
      dietary guidance for Canada.

PMID- 14666497
TI  - An evidence-based approach to the development of national dietary guidelines.
AB  - It has become apparent that confusing and conflicted nutritional advice from the
      media in combination with a quick reversal of policymakers' national nutrition
      recommendations have the potential to lead to public disbelief and cynicism for
      both the process and the conclusions. Consequently, poor design of policy can
      lead to ineffective communications with health professionals and the public. The
      ultimate result is that the public will ignore the recommendations with
      potentially adverse outcomes. Formal evidence-based clinical practice guidelines
      are being used regularly in the medical community. The methodology used to
      develop these guidelines includes a systematic review of the literature,
      filtering the literature for relevant articles, assessing the scientific quality
      of the available evidence, and rating the strength or weakness of the final
      recommendation. This article suggests that national dietary guidelines may be
      improved if they are based on a more formal evidence-based approach. Current
      research that is being conducted to test components of a generic, standardized
      methodology for developing evidence-based population targeted dietary guidelines
      is described.

PMID- 14666498
TI  - Systems for evaluating nutrition research for nutrition care guidelines: do they
      apply to population dietary guidelines?
AB  - Evidence-based medicine has become accepted as the preferred way to develop
      clinical practice guidelines for nutrition care. The distinction between
      nutrition care (ie, medical nutrition therapy) and population dietary guidelines
      is becoming increasingly blurred. The evidence analysis systems used to develop
      Medical Nutrition Therapy Guides for Practice, as well as other medical care
      guidelines, are reviewed. The identification of various methods that evaluate
      individual research reports and various systems that specify the strength of the
      evidence supporting a recommendation/conclusion statement are included within the
      article. The potential application of these systems for development of national
      dietary guidelines is introduced.

PMID- 14666499
TI  - Evaluating the effects of the Dietary Guidelines for Americans on consumer
      behavior and health: methodological challenges.
AB  - The Dietary Guidelines for Americans is the official nutrition policy statement
      for the United States. Government involvement in providing information on private
      behavior, such as food choice, is justified by the high cost of poor diets, as
      measured in medical expenses and lost productivity. The Guidelines are intended
      to provide an up-to-date, consistent information base for federal nutrition
      education and information efforts and food assistance program regulations.
      Through these policy mechanisms, the Guidelines are assumed to improve dietary
      behavior, and, ultimately, health. By law, the Dietary Guidelines for Americans
      must be updated every five years; however, there is no mandate for evaluation.
      Evaluation could provide useful information to assess the extent to which the
      Guidelines positively influence health and provide insights into reasons for
      their successes and limitations. However, evaluation would also present
      considerable challenges. This paper discusses the critical data and
      methodological needs for improving evaluation of the Dietary Guidelines for
      Americans.

PMID- 14666500
TI  - Nutrigenomics: the Rubicon of molecular nutrition.
AB  - The success of the Human Genome Project and the powerful tools of molecular
      biology have ushered in a new era of medicine and nutrition. The pharmaceutical
      industry expects to leverage data from the Human Genome Project to develop new
      drugs based on the genetic constitution of the patient; likewise, the food
      industry has an opportunity to position food and nutritional bioactives to
      promote health and prevent disease based on the genetic constitution of the
      consumer. This new era of molecular nutrition--that is, nutrient-gene interaction
      -can unfold in dichotomous directions. One could focus on the effects of
      nutrients or food bioactives on the regulation of gene expression (ie,
      nutrigenomics) or on the impact of variations in gene structure on one's response
      to nutrients or food bioactives (ie, nutrigenetics). The challenge of the public
      health nutritionist will be to balance the needs of the community with those of
      the individual. In this regard, the excitement and promise of molecular nutrition
      should be tempered by the need to validate the scientific data emerging from the
      disciplines of nutrigenomics and nutrigenetics and the need to educate
      practitioners and communicate the value to consumers-and to do it all within a
      socially responsible bioethical framework.

PMID- 14666501
TI  - Dietary guidelines: some issues to consider before initiating revisions.
AB  - This paper presents two main questions that need to be answered before deciding
      to revise dietary guidelines: Is there really a need to revise existing
      guidelines? and How is dietary risk management to be integrated into dietary
      guidelines? Any group assigned the task of evaluating and possibly revising
      existing guides must answer these questions. It is also critically important to
      specify the exact target group and purpose for any dietary guideline since the
      questions need to be answered in context. This paper addresses some of the
      implications of the recent report on Dietary Reference Intakes for macronutrients
      in its venture into the area of risk management. A major conclusion of the paper
      is that nutrition has entered a new era and that henceforth, as never before,
      risk management, the assessments of likelihood of benefit and risks of harm-as
      well as costs human and financial of our actions-and recommendations must take a
      very prominent position in our work. This is not a role for which most
      nutritionists are prepared and hence it must be seen as a major challenge in the
      preparation of food guides in the future.

PMID- 14666502
TI  - [Instructions and implementations for percutaneous renal biopsy. Guidelines for
      the therapy of glomerular nephropaties].
AB  - This series of articles on the management of glomerulonephritis (GN) has been
      prepared by a team of experts in the evidence-based format consistent with peer
      review of published data. Each author was asked to review the literature for his
      assigned histological type, with emphasis on therapy and limited to adult
      studies. The age limit was not considered for minimal change disease and focal
      segmental glomerulosclerosis, because of the high prevalence of these
      glomerulopathies in children. The particular treatment recommendations for each
      type of glomerular disease were graded by each author according to the amount of
      evidence provided in these reviewed studies. The first two articles concentrate
      on indications and techniques for kidney biopsy. Each subsequent article focuses
      on and describes the highest level of evidence supporting the recommendation for
      therapy in IgA nephropathy (Ig-GN), minimal change nephropathy (MCN) and focal
      segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus
      nephritis, ANCA-associated vasculitis, HCV-associated cryoglobulinaemia and renal
      involvement in paraproteinemic disorders. The article on IgA nephropathy
      emphasises the importance of carefully evaluating both clinical and histologic
      findings before settling on the treatment. The recent, renewed interest in
      steroids and many immunosuppressive agents is discussed in detail.
      Recommendations related to the patient's age are also provided. MCN and FSGS are
      treated together because these forms share similar evidence-based
      recommendations. For both of these diseases, in fact, the initial treatment
      approach in children should be prednisone or prednisolone for four to six weeks.
      The therapeutic response in adults is slower than in children, but adults
      experience fewer relapses and a more prolonged remission. There is also a
      discussion on treatment of relapse, frequent relapsing disease and true steroid
      resistant disease as well as the role of new immunosuppressive agents. Membranous
      nephropathy is a frequent cause of nephrotic syndrome in adults and, in one third
      of these patients, leads to end-stage renal disease. However, the treatment of
      this form is as yet a matter of discussion. Based on extensive critical review of
      the literature, the following recommendations are put forward: (a) no treatment
      in the absence of nephrotic syndrome; (b) patients with heavy proteinuria should
      receive a 6-month treatment with i.v. methylprednisolone (MP) pulse therapy for
      three consecutive days followed by oral MP (0.4 mg/kg/day) (months 1, 3, 5) and
      chlorambucil or cyclophosphamide (months 2, 4, 6); (c) the dosage of chlorambucil
      or cyclophosphamide should be lowered in older patients; (d) cyclosporine is a
      second-choice treatment. The treatment of lupus nephritis depends on the
      histologic class. No specific treatment is usually necessary for class I and IIA.
      Oral steroids are indicated in patients with class IIb, proteinuria and active
      systemic disease. Steroids and azathioprine are the treatment of choice for
      patients with class III and IV, but cyclosporine can be an effective alternative
      therapy. Cyclophosphamide is more effective than azathioprine when severe acute
      renal involvement is present. The treatment of ANCA-associated vasculitis depends
      mainly on clinical presentation, oral prednisone + oral or i.v. cyclophosphamide
      are generally effective. In the most severe cases, the association of MP pulse
      therapy with cyclophosphamide is probably more effective. Plasma exchange is
      probably justified in unresponsive patients. Azathioprine should replace
      cyclophosphamide during the maintenance therapy. In HCV-associated mixed
      cryoglobulinemia the treatment also depends on the severity of renal involvement.
      The treatment for chronic HCV infection involves alpha interferon alone or
      preferably in combination with ribavirin. Aggressive therapy, including i.v. MP,
      plasmapheresis and cyclophosphamide is primarily reserved for patients with acute
      severe disease, as manifested by progressive renal failure, distal necroses
      requiring amputation, or advanced neuropathy. Uncontrolled studies suggest that
      this regimen can improve renal function. Renal involvement is a common problem in
      paraproteinemic disorders that include multiple myeloma, Waldentrom's
      macroglobulinaemia and monoclonal gammopathy. The most common renal diseases in
      this setting are cast nephropathy, primary amyloidosis cast nephropathy, primary
      amyloidosis, and light chain deposition disease that are related to the
      overproduction of monoclonal immunoglobulin light chains. The approach to therapy
      varies with the cause of the renal dysfunction. Patients with amyloidosis or
      light-chain deposition disease are generally treated with chemotherapy, but the
      most effective therapy for myeloma kidney is prevention by minimising the risk
      factors that promote light chain filtration and subsequent obstruction by cast
      formation within the tubules. Chemotherapy or stem cell or bone marrow
      transplantation to decrease filtered light chain load, prevent volume depletion
      and maintain high fluid intake to reduce light chain concentration within the
      tubular lumen are indicated in almost all the patients.

PMID- 14666503
TI  - [Conservative therapy Guidelines for chronic renal failure].
AB  - In recent years, many national and international organizations have developed
      clinical practice guidelines for the most important areas of nephrology. In 1999,
      the Italian Society of Nephrology (SIN) was one of the first scientific societies
      to publish (in Giornale Italiano di Nefrologia) the Guidelines for the Treatment
      of Chronic Renal Failure. Since then, new evidence has accumulated on several
      aspects of the conservative treatment of chronic kidney disease (CKD). These new
      data have been included in the present version of the guidelines. The first
      section of the new guidelines underline the importance of the early detection of
      CKD and early referral to a nephrologist. The second and third sections are
      dedicated to the dietetic treatment of chronic renal failure, even when
      associated with nephrotic syndrome. The fourth section analyzes the anti
      hypertensive treatment of renal failure, focusing on the choice of anti
      hypertensive drugs to retard the progression of renal failure and reduce
      cardiovascular mortality. This section highlights the reno-protective role of ACE
      inhibitors and of AII receptor antagonists in diabetic and nondiabetic
      nephropathies. The Appendix describes methods for the evaluation of the patient's
      nutritional status and for protein intake in chronic renal failure.

PMID- 14666504
TI  - [Guidelines for the treatment of anemia in chronic renal failure].
AB  - Evaluation of anemia: Before beginning epoetin treatment, it is essential to
      evaluate the level of anemia (Hb < 11-12g/dL) by the following measurements: -Hb
      concentration -Red blood cell indices (MCV, MCH, MCHC) -Reticulocyte count -Iron
      stores and availability -C-reactive protein (CRP) Target for anemia treatment:
      The minimum target Hb concentration to be attained is 11 g/dL. The upper limit is
      established individually on a clinical basis. Pending further data, it is
      advisable to maintain and not exceed 12 g/dL for patients with cardiovascular
      disease, diabetes, and graft access. Use of iron: At the start of epoetin
      treatment, 150 mg of iron are needed for every expected increase of 1 g/dL of Hb.
      It is important to achieve and maintain levels of TSAT > 20%, serum ferritin 100
      mcg/L and hypochromic red cells > 6% both before initiating epoetin treatment and
      during its administration. TSAT levels should not persistently exceed > 50% and
      serum ferritin > 500 mcg/L. When administering oral iron the dose should be at
      least 200 mg/die elemental iron; on the other hand, when the intravenous route is
      used, the dose should be 30-60 mg/IV dose in the form of low molecular weight
      salts (iron sodium gluconate) while the higher doses should be reserved for
      patients with transferring levels > 170 mg/dL. Administration of epoetin: The
      dosage of epoetin is individual with more than tenfold variability among
      individuals and all aiming at the same target Hb concentration. There are no
      clinical parameters entirely capable of predicting the necessary dosage.
      Therapeutic range is very wide, without any toxic effects for clinical use up to
      100.000 IU/week. The target Hb concentration is reached in most patients with
      mild anaemia after 2 months' treatment with 4.000-10.000 epoetin (20-50 mcg
      darbepoetin alpha) per week. The HB concentration, along with the reticulocyte
      count, must be checked weekly following initiation and monthly during
      maintenance. Patients with a stable dose-response during conservative therapy may
      require less frequent monitoring (every 2-3 months). Inadequate response to
      epoetin treatment If any resistance is encountered, after excluding all the acute
      and chronic conditions of inadequate response, the reticulocyte count (severe
      reduction in the presence of anti erythropoietin antibodies) and the
      erythropoietin dosage should be measured. The target Hb concentration 11-12 g/dL
      is maintained in 90-95% of the patients by administering 1.000-30.000 IU of
      epoetin (5-150 mcg darbepoetin alpha) per week in the presence of adequate
      reserves of iron. Higher dosages define a state of resistance. Diagnosis of pure
      red cell (PRCA) from anti-erythropoietin antibodies is confirmed by bone marrow
      examination (almost total loss of erythroblasts). If antierythropoietin
      antibodies are present or there is a well founded suspicion of PRCA, the
      administration of epoetin and other similar treatment should be avoided. Side
      effects of epoetin treatment: The treatment of anaemia with epoetin does not
      hasten the progression of CRF. Blood pressure is to be checked regularly during
      initiation of epoetin and the treatment should be discontinued in cases of
      refractory hypertension or hypertensive encephalopathy. There should be increased
      surveillance of graft access, especially in those patients who risk vascular
      depletion. In general, heparin requirements do not increase but it may be
      advisable to evaluate a dose increase. PRCA from anti-erythropoietin antibodies
      has been detected with an incidence ranging from 0.12 to 1.1 cases/every 10
      thousand patients treated.

PMID- 14666505
TI  - [Renal osteodystrophy Guidelines].
AB  - Renal ostedystrophy (ROD) is a major long-term complication in uremic patients.
      Bone histomorphometry still remains the gold standard for the diagnosis of ROD.
      However, the low acceptance grade by patients makes bone biopsy a rarely
      performed and not easily repeatable investigation. No other instrumental
      assessment has been proved as yet to have sufficient sensitivity for ROD
      diagnosis. Many biochemical markers have been proposed for a diagnostic role, but
      few have a real predictive diagnostic value. Serum intact PTH (i-PTH) levels are
      thought to represent a good predictor of bone lesions. However, although a i-PTH
      level greater than 450 pg/mL and lower than 120 pg/mL may well predict high and
      low bone turnover disease respectively, in the wide range of values defined by
      the above border levels i-PTH does not have a predictive role for ROD. There is
      as yet no definite proof that the recently developed PTH assays might increase
      their diagnostic sensitivity. Bone alkaline phosphatase is a more reliable index
      of bone turnover than i-PTH levels. With regards to Al overload, given that an
      iron overburden is excluded, serum Al levels lower than 30 ug/L are seldom
      associated with increased Al deposition; conversely, levels above 60 mg/L are
      highly diagnostic for Al overload. In the latter condition, a DFO test is
      recommended. The main goals of ROD treatment are a) to maintain serum i-PTH
      levels between 120 and 150 pg/mL; b) to bring the phosphate (Pi) concentration
      under 5.5 mg/dL, Ca concentration between 9.2 and 10.4 mg/dL, and the Ca x Pi
      product under 55 mg/dL; c) to bring Al concentration under 20 ug/L; and d) to
      target serum bicarbonate levels between 20 and 24 mmol/L. The main therapeutic
      approaches include: Dietary Pi intake control (< 1200 mg/day). Intestinal
      phosphate binding using calcium salts and sevelamer. Calcium salts must be used
      at a dosage that avoids Ca overload (< 23 g/day). If Pi control is not reached,
      Mg and Al salts may be added at a dose lower than 2 g/day and for less than 3
      months. Appropriate dialysis dose (KT/V > 1.2) and dialysis time (consider
      increased dialysis duration or session number for a week). Ca concentration in
      dialysate and infusion fluids can range between 1.25 and 2.00 mmol/L, according
      to the dialysis technique and to maintain an appropriate Ca balance. Vitamin D
      should not be used when i-PTH levels are < 120 pg/mL and/or serum Ca > 11 mg/dL
      and/or Pi > 6.5 mg/dL. The vitamin D dose should be proportional to PTH levels,
      with a larger dose given as a bolus (23 ug twice or three times per week). The
      intravenous route should be preferred in the case of very high i-PTH (> 700
      pg/mL) or after 3 months of unsuccessful oral treatment. PTX should be prescribed
      on the basis of the clinical, biochemical, and instrumental data. A 7/8 PTX, when
      possible, is the most advisable procedure. Bone transplant disease (BTD) is
      caused by a combination of previous uremic ROD and bone lesions occurring after
      renal transplantation, mainly secondary to steroid effect. The main clinical
      result of BTD is the osteopenicosteoporotic syndrome, which frequently results in
      bone fractures. The most effective treatment of BTD is a reduction of the
      cumulative steroid dose. No strong evidence has been produced as yet for a
      preventive role of either bisphosphonates or vitamin D supplementation on BTD.

PMID- 14666506
TI  - [Guidelines for diagnosis and therapy of diabetic nephropathy].
AB  - The incidence of diabetes as cause of end-stage renal failure (ESRF) has
      significantly increased, and will continue to grow during the next few years.
      Moreover, diabetic nephropathy is associated with elevated cardiovascular
      morbidity and mortality. These guidelines focus on the possible intervention
      strategies to prevent and treat ESRF in diabetic patients. In normoalbuminuric
      patients, glycated haemoglobin levels less than and equal to 7.5% is mandatory
      for reducing the risk of incipient nephropathy. Furthermore, blood pressure
      levels < 130/80 mmHg are strongly recommended. In microalbuminuric patients,
      glycated hemoglobin levels below 7.5% and blood pressure levels below 130/80 mmHg
      (120/70-75 mmHg in patients < 50 years) are recommended. Moreover, there is
      evidence that inhibition of the rennin-angiotensin-aldosterone system, either by
      angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin II receptor
      antagonists (AIIRA) is able to reduce the incidence of overt nephropathy,
      regardless of blood pressure levels. Current guidelines recommed ACE-I as the
      first-choice drug in type 1 diabetes, while both ACE-I and AAIRA are considered
      first-choice therapy in type 2 diabetes. In proteinuric patients it is uncertain
      whether glycemic control affects the progression of nephropathy, which in turn is
      dramatically influenced by blood pressure. Optimal blood pressure levels are
      below 130/80 mmHg (120/70-75 mmHg in patients < 50 years). In type 1 diabetes
      there is consensus on the renoprotective role of ACE-1. In type 2 diabetes, two
      recent trials demonstrated that AIIRA are more effective than conventional
      therapy or calcium channel blockers in slowing down the progression of
      nephropathy. ACE-I are indeed recommended as first-choice drugs in type 1
      diabetes while AIIRA are the first-choice agents for ESRF prevention in type 2
      diabetes. Dialysis treatment should be started as soon as the creatinine
      clearance is reduced to about 10-15 mL/min. The choice of dialysis schedule
      should be individualized according to clinical and adequacy criteria (CAPD weekly
      Kt/V > or = 2 and single HD session Kt/V > or = 1.5). Simultaneous pancreas
      kidney transplantation should be the first-choice therapeutic option in type 1
      diabetes, while renal transplantation has been demonstrated to significantly
      improve the prognosis of type 2 diabetes patients with ESRF.

PMID- 14666507
TI  - [Guidelines of the Italian Society of Nephrology. Peritoneal dialysis
      Guidelines].
AB  - The adequate dosage of peritoneal dialysis (PD) has been defined (using
      unrandomized and uncontrolled studies) asKt/V = 2, with a total (peritoneal +
      renal) creatinine clearance = 60 mL/min. The recent prospective, randomized
      ADEMEX study, suggests targets of 1.8 and 54 mL/min respectively. Dialysis must
      also be adequate to control fluid removal, phosphate levels, nutritional status,
      and hypertension. The targets for automated PD (APD) should be either 10% more
      than CAPD or similar, depending on the time of blood sample collection either
      immediately at the end of the automated exchanges or 6 to 8 hours after. A
      peritoneal equilibration test should be done 1 to 2 months after the start of PD,
      yearly, and when peritoneal permeability or ultrafiltration changes occurr.
      Residual renal function must be protected as long as possible by avoiding
      nephrotoxic drugs and excessive dehydration. Every effort must be taken in the
      attempt to maintain a good nutritional status and to diagnose as soon as possible
      any changes toward malnutrition. Hypertension has a high prevalence in PD
      patients and has negative effects on both cardiovascular status and patient
      survival. However, anti-hypertensive therapy should avoid hypotension, mainly in
      older patients, who are more at risk for cerebrovascular accident.
      Hyperparathiroidism must be controlled by diet, phosphate binders, and calcitriol
      supplement, but attention must be paid to avoid cardiac and vascular
      calcifications. Peritonitis and exit-site infection should be prevented by all
      means available. In the case of infection, empiric antibiotic therapy should be
      started as soon as possible and then adapted according to the antibiogram.

PMID- 14666508
TI  - Disruption of the genomic imprint in trans with homologous recombination at Snrpn
      in ES cells.
AB  - In gene targeting studies of the Prader-Willi syndrome (PWS)/Angelman syndrome
      (AS) domain in mouse ES cells, we recovered only recombinants with the paternal
      allele for constructs at exons 2 or 3 of the imprinted, maternally silenced Snurf
      Snrpn gene. These sites lie close to the imprinting center (IC) for this domain.
      In contrast, recombinants for Ube3a within the same imprinted domain were
      recovered with equal frequency on the maternal and paternal alleles. In addition,
      gene targeting of the paternal allele for Snurf-Snrpn resulted in partial or
      complete demethylation in trans with activation of expression for the previously
      silenced maternal allele. The imprint switching of the maternal allele in trans
      is not readily explained by competition for trans-acting factors and adds to a
      growing body of evidence indicating homologous association of oppositely
      imprinted chromatin domains in somatic mammalian cells.

PMID- 14666509
TI  - Tetraploid embryos rescue the early defects of tw5/tw5 mouse embryos.
AB  - tclw5 is a t-complex recessive lethal mutation of the tw5-haplotype. Since
      tw5/tw5 embryos die soon after implantation, the tclw5 gene is thought to play an
      important role in early embryogenesis. Previous histological studies have
      demonstrated that tw5 homozygotes do not survive past the gastrulation stage due
      to extensive death of the embryonic ectoderm, whereas the extraembryonic tissues
      were less affected. In the present study, we demonstrate that tw5/tw5 embryos may
      be distinguished from wildtype littermates at embryonic (E) day 5.5. At this
      stage, the visceral endoderm of tw5/tw5 embryos appeared to be different,
      possessing smaller and fewer vacuoles compared to normal littermates. This led us
      to hypothesize that the visceral endoderm may be affected by tclw5. Confirmation
      was provided by the rescue of tw5/tw5 embryos following aggregation with
      tetraploid embryos. However, rescued embryos did not survive past E9.0 and
      displayed an underdeveloped posterior region. This would indicate that the
      actions of tclw5 extend beyond the midgestation stage.

PMID- 14666510
TI  - Generation of a germ cell nuclear factor conditional allele in mice.
AB  - Two recombination steps in embryonic stem (ES) cells were adopted to generate a
      floxed Germ Cell Nuclear Factor (GCNF) allele. First, a targeting vector
      containing a loxP site upstream of exon 4, encoding the DNA binding domain (DBD),
      and a floxed NeoTK double selection cassette downstream of exon 4 was integrated
      into the GCNF locus by homologous recombination. Second, a Cre-expressing vector
      was transiently introduced to remove the floxed NeoTK cassette via site-specific
      recombination. Heterogeneous ES cell populations were found in a single colony
      after Cre transfection and were separated using an ES cell re-pick step. Floxed
      GCNF mice were generated and had normal GCNF expression in the adult gonads.
      Using the Msx2Cre transgenic mice, the floxed GCNF can be completely deleted in
      the female germline. Taken together, the floxed GCNF mice were successfully
      generated and female germline deletion of the floxed GCNF allele was achieved
      using Msx2Cre mice.

PMID- 14666511
TI  - Electroporation of cynomolgus monkey embryonic stem cells.
AB  - Efficient genetic modification of primate embryonic stem (ES) cells is essential
      for the application for both basic and preclinical research. The transfection
      efficiency of primate ES cells is reportedly lower than that of mouse ES cells.
      Cynomolgus monkey ES cells provide a powerful model for understanding human
      development and disease. We evaluated electroporation as a method to introduce
      foreign genes into cynomolgus monkey ES cells. Our examination has allowed us to
      establish a protocol producing about 100 stably transfected clones from 10(7)
      cynomolgus monkey ES cells. Differences in efficiency, however, were observed for
      other ES cell lines. We compared the transcriptional activities of the PGK-1,
      CMV, and SV40 promoters in cynomolgus monkey ES cells generating efficient G418
      selection. Although the PGK-1 and SV40 promoters efficiently drove neo gene
      expression, the CMV promoter was significantly less transcriptionally active in
      cynomolgus monkey ES cells. Using this electroporation method, we established
      fluorescent cynomolgus monkey ES cell lines. These cells may be useful tools for
      tracing grafted cells in transplantation studies using a variety of functional
      cells derived from cynomolgus monkey ES cells.

PMID- 14666512
TI  - Dlx5/6-enhancer directed expression of Cre recombinase in the pharyngeal arches
      and brain.
AB  - Dlx5 and Dlx6, two members of the Distalless gene family, are required for
      development of numerous tissues during embryogenesis, including facial and limb
      development. This gene pair is expressed in tandem, transcribed toward each other
      and separated by a short intergenic region containing multiple putative
      enhancers. Targeted inactivation of Dlx5 and Dlx6 in mice results in multiple
      developmental defects in craniofacial and limb structures, suggesting that these
      genes are crucial for aspects of both neural crest and nonneural crest
      development. To further investigate potential developmental roles of Dlx5 and
      Dlx6, we used one of the Dlx5/6 intergenic enhancers to drive Cre recombinase
      expression in transgenic mice. Crossing Dlx5/6-Cre transgenic mice with mice from
      the R26R strain results in beta-galactosidase staining in the apical ectodermal
      ridge, brain, and neural crest-derived mesenchyme of the pharyngeal arches, with
      staining in term embryos observed in the facial skeleton and specific brain
      structures. However, in contrast to endogenous expression patterns of Dlx5 and
      Dlx6, Cre expression within the pharyngeal arches occurs during a very narrow
      window in early development. Our studies suggest that Dlx5/6-Cre mice may prove
      useful both in further understanding the function and regulation of Distalless
      genes during development and in studies of gene function in conditional knockout
      mice.

PMID- 14666513
TI  - De novo DNA methylation at the CpG island of the zebrafish no tail gene.
AB  - The zebrafish no tail gene (ntl) is indispensable for the formation of the
      notochord and the tail structure. Here we showed that de novo DNA methylation
      occurred at the CpG island of ntl. The methylation started at the segmentation
      stage and continued after the larval stage. However, it occurred predominantly
      between 14 and 48 h postfertilization, which overlaps the period in which ntl
      expression disappears in the notochord and the tailbud. This inverse correlation,
      together with the methylation-associated formation of an inaccessible chromatin
      structure at the ntl CpG island region, suggested the involvement of the de novo
      methylation in ntl repression. Since no changes in methylation patterns were
      observed at the CpG islands of four other zebrafish genes, there must be a
      mechanism in zebrafish for specific methylation of the ntl CpG island.

PMID- 14666514
TI  - Amyloid beta-protein fragment 31-35 suppresses delayed rectifying potassium
      channels in membrane patches excised from hippocampal neurons in rats.
AB  - To clarify the early initial mechanism underlying the neurotoxicity of amyloid
      beta-protein (AbetaP) and the shorter essential active sequence in native AbetaP
      molecules, the effects of AbetaP31-35 and AbetaP25-35 on delayed rectifier K+
      current (Ik) were investigated in the inside-out membrane patches excised from
      hippocampal neurons of rats. The results showed that: 1) After application of
      AbetaP31-35 (5 microM) to the inside of patches, the average open frequency and
      open probability of Ik channels reversibly decreased by 70.45 +/- 35.75% and 86.9
      +/- 11.13%, respectively; the mean open time decreased by 47.1 +/- 38.8%, while
      the mean current amplitude of Ik channels was not significantly affected. 2)
      Application of AbetaP25-35 at the same concentration showed similar effects as
      did the AbetaP31-35 application. It has generally been accepted that AbetaP25-35
      acts as a full-length AbetaP molecule does, so our findings suggest that the
      neurotoxicity of AbetaP may be initiated by the functional suppression of Ik
      channels and the sequence of 31-35 might be the shorter active sequence in AbetaP
      responsible for its neurotoxicity.

PMID- 14666515
TI  - Chemical anatomy of the human paraventricular thalamic nucleus.
AB  - The paraventricular thalamic nucleus (Pa) lies in the most medial aspect of the
      thalamus and is considered one of the midline thalamic nuclei. In the present
      study, we carried out histochemical and immunohistochemical procedures in the Pa
      of normal individuals to visualize the pattern of distribution of
      acetylcholinesterase (AChE), calbindin D-28k (CB), parvalbumin (PV), calretinin
      (CR), limbic system-associated membrane protein (LAMP), substance P (SP), and
      enkephalin (ENK). Other cytoarchitectural and myeloarchitectural techniques, such
      as Nissl and Gallyas, were also employed to delineate the boundaries of the Pa.
      The main findings of this study are: 1) AChE staining in the Pa was
      heterogeneously distributed along its anteroposterior and mediolateral axes; 2)
      the Pa harbored numerous CB- and CR-immunoreactive (ir) cells and neuropil, but
      this nucleus was largely devoid of PV; 3) the Pa was highly enriched in LAMP and
      this protein appeared uniformly distributed through its whole extent; and, 4) the
      SP and ENK immunoreactivities in the Pa revealed numerous highly varicose fibers
      scattered throughout this nucleus, but no stained cells. This morphological study
      demonstrates that the Pa is a heterogeneous chemical structure in humans. The
      functional significance of these results is discussed in the light of similar
      data gathered in several mammalian species.

PMID- 14666516
TI  - Transplantation and restoration of functional synapses between an identified
      neuron and its targets in the intact brain of Lymnaea stagnalis.
AB  - Most information available to date regarding the cellular and synaptic mechanisms
      of target cell selection and specific synapse formation has primarily come from
      in vitro cell culture studies. Whether fundamental mechanisms of synapse
      formation revealed through in vitro studies are similar to those occurring in
      vivo has not yet been determined. Taking advantage of the regenerative
      capabilities of adult molluscan neurons, we demonstrate that when transplanted
      into the host ganglia an identified neuron reestablishes its synaptic connections
      with appropriate targets in vivo. This synaptogenesis, however, was possible only
      if the targets were denervated from the host cell. Specifically, the giant
      dopamine neuron right pedal dorsal 1 (RPeD1) located in the pedal ganglia was
      isolated from a donor brain and transplanted into the visceral ganglia of the
      recipient brain. We discovered that within 2-4 days the transplanted RPeD1
      exhibited extensive regeneration. However, simultaneous intracellular recordings
      failed to reveal synapses between the transplanted cell and its targets in the
      visceral ganglia, despite physical overlap between the neurites. To test whether
      the failure of a transplanted cell to innervate its target was due to the fact
      that the targets continued to receive input from the native RPeD1, the latter
      soma was surgically removed prior to the transplantation of RPeD1. Even after the
      removal of host soma, the transplanted RPeD1 failed to innervate the targets such
      as visceral dorsal 4 (VD4)-despite extensive regeneration by the transplanted
      cell. However, when RPeD1 axon was allowed to degenerate completely, the
      transplanted RPeD1 successfully innervated all of its targets and these synapses
      were similar to those seen between host RPeD1 and its targets. Taken together,
      our data demonstrate that the transplanted cells will innervate their potential
      targets only if the targets were denervated from the host cell. These data also
      lend support to the idea that, irrespective of their physical location in the
      brain, the displaced neurons are able to regenerate, recognize their targets, and
      establish specific synapses in the nervous system.

PMID- 14666517
TI  - Opioid-mediated modulation of calcium currents in striatal and pallidal neurons
      following reserpine treatment: focus on kappa response.
AB  - Previous work has shown that enkephalins target N-type calcium (Ca2+) channels in
      striatal and globus pallidus (GP) neurons, principally through activation of mu
      like receptors. Here, we examined the effects of selective mu, delta, and kappa
      agonists on Ca2+ currents in striatal and GP neurons isolated from either control
      or reserpine-treated rats. In cells from control rats DAMGO and dynorphin (DYN)
      inhibited high-voltage-activated (HVA) Ca2+ currents preferentially in "medium-to
      small" GP cells (likely to correspond to parvalbumin-negative cells). The kappa
      response was elicited by several agonists (DYN 17, DYN 13, BRL, U50-488-H), U50
      488-H being the most effective (>30% maximal inhibition). U50-488-H affected both
      omega-CgTxGVIA-sensitive and nimodipine-sensitive Ca2+ conductances. The kappa
      mediated effect (but not the mu response) was slow and blocked by chelerythrine,
      supporting the involvement of protein kinase C. In neurons from reserpinized rats
      we observed modest changes in the mu-inhibited fraction in small GP cells and a
      dramatic reduction of the kappa-sensitive fraction in principal striatal cells.
      These data imply that aminergic depletion alters opiate transmission
      differentially in the indirect and direct pathways. The suppression of the kappa
      response only in striatum reinforces the notion of an imbalance of endogenous
      opiates as relevant in extrapyramidal motor dysfunctions.

PMID- 14666518
TI  - Temporal characterisation of amphetamine-induced dopamine release assessed with
      [11C]raclopride in anaesthetised rodents.
AB  - Competition between endogenous neurotransmitters and radiolabelled tracers, as
      measured by positron emission tomography (PET), may provide a measure of
      endogenous neurotransmitter flux in vivo. For example, carbon-11 labelled
      raclopride has been effectively used to monitor dopamine release following
      pharmacological and behavioural manipulations. The current study describes a
      rodent model of amphetamine-induced [11C]raclopride reduction, which allowed the
      characterisation of the dose-response and temporal dynamics of this reduction
      over a 24-h time course. Over the range studied, a monotonic dose-response
      relationship between amphetamine dose and [11C]raclopride reduction was observed.
      When compared with previously published microdialysis data, an approximate 16%
      reduction in [11C]raclopride binding potential was associated with a
      approximately 25-fold increase in extracellular dopamine. A reduction of 20-30%
      in raclopride binding was observed 30 min after amphetamine injection (4 mg/kg
      i.p.). This reduction in [11C]raclopride binding persisted for 4 h but returned
      to baseline by 8 h. The data suggest a persistent amphetamine-induced raclopride
      displacement in rodents and reinforce findings from nonhuman primates that a
      simple competitive occupancy model may not adequately explain the temporal
      characteristics of the amphetamine-induced decrease in radiotracer binding.

PMID- 14666519
TI  - Intensification of cataleptic response in 6-hydroxydopamine-induced
      neurodegeneration of substantia nigra is not dependent on the degree of dopamine
      depletion.
AB  - An intensification of catalepsy has been observed upon repeated testing in rats
      with permanent neurodegeneration of substantia nigra. Here, the question is
      addressed whether the rate of development of intensification of catalepsy upon
      repeated testing in the same context is dependent on dopamine level in the basal
      ganglia. Rats were lesioned with 2 microg or 6 microg of 6-hydroxydopamine in the
      median forebrain bundle to produce dopamine depletion in substantia nigra in two
      different proportions. Both groups were exposed to catalepsy tests for 7
      successive days in the same context, and the context was changed on day 8. On day
      9 the catalepsy test was repeated with the old context. After the completion of
      the behavioral experiments, various regions of basal ganglia were analyzed for
      dopamine and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methyl tyronine,
      and homovanillic acid. Lesions with 6 microg of 6-hydroxydopamine produced strong
      dopamine depletion (78%) and akinetic response in the catalepsy test on day 1.
      Repeated exposure of this group to the catalepsy tests in the same context
      produced intensification of cataleptic response. Changing the context on day 8
      reduced catalepsy. Performing the experiments again with the old context on day 9
      produced an intensified response. Lesions with 2 microg of 6-hydroxydopamine
      produced partial dopamine depletion (46%) without any motor disturbances.
      However, repeated exposure and context changes produced a similar pattern of
      catalepsy as in the 6 microg lesioned animals. These results indicate that the
      rate of building up of intensification of catalepsy is not dependent on the
      degree of dopamine depletion. It signifies the importance of context in the
      expression and augmentation of parkinsonian symptoms during the course of the
      disease to subjects with subthreshold dopaminergic neurodegeneration that could
      not produce motor disturbances alone. Prevention of context-dependent
      intensification of catalepsy could be beneficial in the treatment of Parkinson's
      disease.

PMID- 14666520
TI  - Roles of actin networks in peristaltic squeezing of sperm bundles in Bombyx mori.
AB  - Two types of sperm are produced in the silkworm, Bombyx mori. Nucleate eupyrene
      sperm is an ordinary sperm that contributes to fertilization, while anucleate
      apyrene sperm is considered to play important roles in assisting eupyrene sperm.
      At the very late stage of spermatogenesis, a phenomenon called "peristaltic
      squeezing" occurs in both types of sperm, whereby cytoplasm of the eupyrene and
      nuclei of the apyrene sperm are discarded from the posterior end, forming matured
      sperm. In this study, rhodamine-phalloidin staining for actin was applied to
      sperm bundles. Before the start of peristaltic squeezing, actin filament networks
      are spread on the cyst cells and constrictions by the networks appear in several
      places of the bundles. Actin particles, which are later recognized as circlets,
      are localized within the bundles. Squeezing action by the networks occurs from
      the anterior region and transfers toward the posterior, eliminating cytoplasm
      together with circlets from the posterior end. It seems that actin filaments
      contribute to the peristaltic squeezing of the sperm bundles in Bombyx mori.

PMID- 14666521
TI  - Blubber development in bottlenose dolphins (Tursiops truncatus).
AB  - Blubber, the lipid-rich hypodermis of cetaceans, functions in thermoregulation,
      buoyancy control, streamlining, metabolic energy storage, and locomotion. This
      study investigated the development of this specialized hypodermis in bottlenose
      dolphins (Tursiops truncatus) across an ontogenetic series, including fetuses,
      neonates, juveniles, subadults, and adults. Blubber samples were collected at the
      level of the mid-thorax, from robust specimens (n = 25) that stranded along the
      coasts of North Carolina and Virginia. Blubber was dissected from the carcass and
      its mass, and the depth and lipid content at the sample site, were measured.
      Samples were prepared using standard histological methods, viewed by light
      microscopy, and digital images of blubber captured. Images were analyzed through
      the depth of the blubber for morphological and structural features including
      adipocyte size, shape, and numbers, and extracellular, structural fiber
      densities. From fetus to adult, blubber mass and depth increased proportionally
      with body mass and length. Blubber lipid content increased dramatically with
      increasing fetal length. Adult and juvenile blubber had significantly higher
      blubber lipid content than fetuses, and this increase was reflected in mean
      adipocyte size, which increased significantly across all robust life history
      categories. In juvenile, subadult, and adult dolphins, this increase in cell size
      was not uniform across the depth of the blubber, with the largest increases
      observed in the middle and deep blubber regions. Through-depth counts of
      adipocytes were similar in all life history categories. These results suggest
      that blubber depth is increased during postnatal growth by increasing cell size
      rather than cell number. In emaciated adults (n = 2), lipid mobilization, as
      evidenced by a decrease in adipocyte size, was localized to the middle and deep
      blubber region. Thus, in terms of both lipid accumulation and depletion, the
      middle and deep blubber appear to be the most metabolically dynamic. The
      superficial blubber likely serves a structural role important in streamlining the
      animal. This study demonstrates that blubber is not a homogeneous tissue through
      its depth, and that it displays life history-dependent changes in its morphology
      and lipid content.

PMID- 14666522
TI  - Induction of the avian coelom with associated vitelline blood circulation by
      Rauber's sickle derived junctional endoblast and its fundamental role in heart
      formation.
AB  - In histological sections through chicken blastoderms of different ages we
      describe the temporospatial relationship between junctional endoblast, the
      formation of blood islands (appearing first from a peripherally migrating
      mesoblastic blastema), and the formation of coelomic vesicles developing later
      in/and from a more superficially extending mesoblastic blastema (coelomic
      mesoblast). After unilateral removal of the Rauber's sickle-derived junctional
      endoblast in early streak blastoderms (stage 2-4; Vakaet [1970] Arch Biol 81:387
      426) and culture to stage 11 (Hamburger and Hamilton [1951] J Morphol 88:49-92),
      we observed that the early formation of the coelomic cavity was locally or
      totally disturbed in the operated area. Besides the simultaneous absence of blood
      islands, the coelomic vesicles did not form normally. Instead of regularly
      aligned coelomic vesicles, progressively forming the coelomic cavity by fusion,
      some voluminous irregular cavities appeared. Thus, the extent of the coelomic
      cavity was greatly reduced and the operated side was considerably smaller than
      the unoperated side. Furthermore, in the youngest operated blastoderms the
      cranial portion of the involved coelomic cavity (hemipericardial cavity)
      exhibited rudimentary development and usually did not reach the region of the
      foregut endoderm. This resulted in the absence of the myoepicardium and
      associated endocardium at this side. In another experiment, after removal of the
      junctional endoblast at one side of the chicken blastoderm, a fragment of quail
      junctional endoblast was placed isotopically. This resulted, after further in
      vitro culture, in the restoration of the formation of coelomic vesicles and
      accompanying subjacent blood islands in the immediate neighborhood of the apposed
      quail junctional endoblast. Also, the pericardium and primary heart tube
      developed normally. Similarly, by using the quail-chicken chimera technique, we
      demonstrated that the splanchnic mesoderm cells of the pericardium develop in
      intimate association with the most cranial part of the junctional endoblast
      (derived from the Rauber's sickle horns). Our experiments indicate that the
      coelom and, in particular, the pericardium and primary heart tube form
      progressively (in time and space) under the inductory influence of Rauber's
      sickle and junctional endoblast.

PMID- 14666523
TI  - Effects of noradrenaline administration on the interrenal gland of the newt,
      Triturus carnifex: evidence of intra-adrenal paracrine interactions.
AB  - The existence of paracrine control of steroidogenic activity by adrenochromaffin
      cells in Triturus carnifex was investigated by in vivo noradrenaline (NA)
      administration. The effects were evaluated by examination of the ultrastructural
      morphological and morphometrical features of the tissues as well as the serum
      levels of aldosterone, NA, and adrenaline (A). In March and July, NA
      administration increased aldosterone release (from 187.23 +/- 2.93 pg/ml to
      878.31 +/- 6.13 pg/ml in March; from 314.60 +/- 1.34 pg/ml to 622.51 +/- 2.65
      pg/ml in July) from steroidogenic cells. The cells showed clear signs of
      stimulation, as evidenced by a strong reduction of lipid content. Moreover, NA
      administration decreased the mean total number of secretory vesicles in the
      chromaffin cells in March (from 7.24 +/- 0.18 granules/micro2 to 5.57 +/- 1.88
      granules/micro2) and July (from 7.74 +/- 0.74 granules/micro2 to 6.04 +/- 1.13
      granules/micro2). In March, however, when T. carnifex chromaffin cells contain
      both catecholamines, NA (3.88 +/- 0.13 granules/micro2) and A (3.36 +/- 0.05
      granules/micro2) in almost equal quantities, NA administration reduced A content
      (1.29 +/- 1.04 granules/micro2) in the chromaffin cells, enhancing adrenaline
      secretion (from 681.27 +/- 1.83 pg/ml to 1527.02 +/- 2.11 pg/ml). In July, when
      the chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86
      granules/micro2; A: 0.32 +/- 0.13 granules/micro2), NA administration reduced the
      number of NA granules (5.45 +/- 1.10 granules/micro2), thereby increasing
      noradrenaline release from the chromaffin cells (from 640.19 +/- 1.65 pg/ml to
      1217.0 +/- 1.14 pg/ml). The results of this study indicate that NA influences the
      steroidogenic cells, eliciting aldosterone release. Noradrenalin effects on the
      chromaffin cells, increase of NA or A secretion, according to the period of
      chromaffin cell functional cycle, may be direct and/or mediated through the
      steroidogenic cells. The existence of intra-adrenal paracrine interactions in T.
      carnifex is discussed.

PMID- 14666524
TI  - Pattern and rate of ovary differentiation with reference to somatic development
      in anuran amphibians.
AB  - The rate of somatic development of anuran amphibians is only roughly correlated
      with the rate of gonad differentiation and varies among species. The somatic
      stage of a tadpole often does not reflect its age, which seems to be crucial for
      gonad differentiation rate. We compared the morphology and differentiation of
      developing ovaries at the light and electron microscopy level, with reference to
      somatic growth and age of a female. Our observations were performed on 12 species
      of six families (Rana lessonae, R. ridibunda, R. temporaria, R. arvalis, R.
      pipiens, R. catesbeiana, Bombina bombina, Hyla arborea, Bufo bufo. B. viridis,
      Xenopus laevis, Pelobates fuscus) and compared with the results obtained by other
      authors. This allowed us to describe the unified pattern of anuran female gonad
      differentiation. Ovary differentiation was divided into 10 stages: I-III,
      undifferentiated gonad; IV, sexual differentiation; V, first nests of meiocytes;
      VI, first diplotene oocytes; VII-IX, increasing number of diplotene oocytes and
      decreasing number of oogonia and nests; X, fully developed ovary composed of
      diplotene oocytes with rudimental patches of oogonia. We distinguished three
      types of ovary differentiation rate: basic (most species), retarded (genus Bufo),
      and accelerated (green frogs of the subgenus Pelophylax genus Rana).

PMID- 14666525
TI  - A pair of rosette glands in the embryo and zoeal larva of an estuarine crab
      Sesarma haematocheir, and classification of the tegumental glands in the embryos
      of other crabs.
AB  - A pair of rosette glands (one of the tegumental glands in crustaceans) is present
      at the root of the dorsal spine of the thorax in mature embryos of the estuarine
      crab Sesarma haematocheir. Each rosette gland is spherical, 45-50 microm in
      diameter. This gland consists of three types of cells: 18-20 secretory cells, one
      central cell, and one canal cell. The secretory cells are further classified into
      two types on the basis of the morphology of secretory granules. There are 17-19 a
      cells, and only one b cell per rosette gland. An a cell contains spherical
      secretory granules of 2-3 microm in diameter. The granules are filled with highly
      electron-dense materials near the nucleus but have lower electron-density near
      the central cell. The secretory granules contained in the b cell have an
      irregular shape and are 1-1.5 microm in diameter. The density of the materials in
      the granules is uniform throughout the cytoplasm. The secretory granules
      contained in both the a and b cells are produced by the rough endoplasmic
      reticulum. Materials in the granules are exocytotically discharged into the
      secretory apparatus inside the secretory cell, sent to the extracellular channels
      in the central cell, and secreted through the canal cell. The rosette gland can
      be distinguished from the epidermal cells 2 weeks after egg-laying and the gland
      matures just before hatching. Materials produced by this gland are secreted after
      hatching and secretion continues through five stages of zoeal larvae. These
      rosette glands were never found in the megalopal larva. Rosette glands are found
      in the embryos of Sesarma spp. and Uca spp. In other crabs, tegumental glands are
      also found at the same position as in the embryo of S. haematocheir, but the fine
      structure of their glands is largely different from that of the rosette gland. On
      the basis of the morphology of secretory cells (a-g cell types), the tegumental
      glands of a variety of crab embryos can be classified into four types, including
      rosette glands (type I-IV). The function of these tegumental glands is not yet
      known, but different types of the gland seem to reflect the phylogeny of the
      crabs rather than differences of habitat.

PMID- 14666526
TI  - Morphogenesis of parrot jaw muscles: understanding the development of an
      evolutionary novelty.
AB  - Parrots have developed novel head structures in their evolutionary history. The
      appearance of two new muscles for strong jaw adduction is especially fascinating
      in developmental and evolutionary contexts. However, jaw muscle development of
      parrots has not been described, despite its uniqueness. This report first
      presents the normal developmental stages of the cockatiel (Nymphicus
      hollandicus), comparable to that of the chick. Next, the peculiar skeletal
      myogenesis in the first visceral arch of parrots is described, mainly focusing on
      the development of two new jaw muscles. One of the parrot-specific muscles, M.
      ethmomandibularis, was initially detected at Nymphicus Stage 28 (N28) as the
      rostral budding of M. pterygoideus. After N32, the muscle significantly elongates
      rostrodorsally toward the interorbital septum, following a course lateral to the
      palatine bone. Another parrot-specific muscle, M. pseudomasseter, was first
      recognized at N36. The muscle branches off from the posteromedial M. adductor
      mandibulae externus and grows in a dorsolateral direction, almost covering the
      lateral surface of the jugal bar. The upper tip of the muscle is accompanied by
      condensed mesenchyme, which seems to be derived from cephalic neural crest cells.

PMID- 14666527
TI  - Histology and ultrastructure of the gut epithelium of the neotenic cave
      salamander, Proteus anguinus (Amphibia, Caudata).
AB  - Histological, histochemical, and ultrastructural features of the gut of the
      European endemic cave salamander Proteus anguinus were studied. The gut is a
      relatively undifferentiated muscular tube lined with a simple columnar epithelium
      containing numerous goblet cells. The mucosa and underlying lamina
      propria/submucosa are elevated into a number of high longitudinal folds
      projecting into the lumen. The enterocytes are covered apically with uniform
      microvilli. Irregularity in the arrangement of microvilli was observed.
      Occasionally, irregular protrusions of the cytoplasm appear between groups of
      microvilli. Pinocytotic activity occurs at the bases of the intermicrovillous
      space. Mitochondria are numerous in the apical cytoplasm and basally beneath the
      nuclei. The supranuclear cytoplasm contains most of the cell organelles. The
      lateral plasma membranes of adjacent cells interdigitate and are joined by
      junctional complexes. The periodic acid-Schiff (PAS) reaction, indicating neutral
      mucosubstances, is positive only in the apical brush border of enterocytes and in
      goblet cells. The goblet cells also stained with Alcian blue (AB), at pH 2.5,
      thus revealing the presence of carboxylated glycosaminoglycans. Compact
      aggregations of AB- and PAS-negative cells are situated directly below the
      epithelium. Mitotic figures are present in individual clusters of cells. The fine
      structure of cells in these clusters indicated that these cells could be
      responsible for renewal of intestinal epithelium. Numerous endocrine-like cells
      could also be seen. The closely packed smooth muscle cells and amorphous
      extracellular material with collagen fibrils constitute a net-like structure
      under the basal lamina that is very closely associated with the epithelium. There
      are numerous acidophilic granular cells between epithelial cells, in the lamina
      propria/submucosa, and between cells aggregations. They seem to be associated
      with nematode infections and possibly constitute a humoral defense mechanism.

PMID- 14666528
TI  - Ovarian histology of the placentotrophic Mabuya mabouya (Squamata, Scincidae).
AB  - Ovarian structure and folliculogenesis of females at different reproductive
      stages are described for the viviparous placentotrophic lizard Mabuya mabouya.
      The small ovaries have a thin wall formed by the ovarian epithelium and a thin
      tunica albuginea. One to two germinal beds that contain numerous oogonia and
      developing primordial follicles are derived from the ovarian epithelium and are
      next to the ovarian hilum. The ovarian cortex contains follicles at different
      stages of development, corpora lutea, and atretic follicles. The yolk nucleus and
      Balbiani complex were not evident in the ooplasm of previtellogenic follicles.
      The follicular epithelium of these follicles is polymorphic, as in other species
      of Squamata, but the larger cells are spherical and monolayered rather than
      pyriform. The zona radiata of the preovulatory follicles is less developed than
      in lecithotrophic species. These features suggest a decrease in metabolic and
      absorptive processes during follicular growth. In preovulatory follicles (1.5-1.8
      mm diameter), primordial yolk vacuoles and small cortical granules are deposited
      in the ooplasm instead of fatty yolk platelets, so that only one stage of
      vitellogenesis is observed. Polyovular atretic follicles occur in some females.
      Follicular atresia is minimal for preovulatory follicles, but is more frequent in
      follicles with polymorphic epithelia. In the corpus luteum, the luteal tissue is
      formed from granulosa cells and luteolysis occurs during the late gastrula --
      late neurula embryonic stages. Thus, the maintenance of gestation from the
      pharyngula to preparturition stages seems to be related to secretion of
      extraluteal progesterone, possibly of placental origin. These observed ovarian
      features are related to the high degree of placental complexity of this species
      and show that the evolution of advanced placentotrophy in species of this lineage
      has been accompanied by concomitant changes in ovarian function.

PMID- 14666529
TI  - Studies of male sexual tubes in hermit crabs (crustacea, decapoda, anomura,
      paguroidea). I. Morphology of the sexual tube in Micropagurus acantholepis
      (Stimpson, 1858), with comments on function and evolution.
AB  - The external morphology and internal structure of the male sexual tube of the
      hermit crab Micropagurus acantholepis, a member of the family Paguridae from
      Australian waters, is described in detail using histological thick sectioning and
      scanning and transmission electron microscopy techniques. This is the first in
      depth study of a sexual tube in the Paguroidea, a group where a remarkable number
      of genera (55.9% in the family Paguridae) with species having these intriguing
      sexual structures are known. In M. acantholepis a sexual tube is present on the
      left side, whereas only a gonopore is present on the right side. The tube is used
      for the delivery of spermatophores to the female and consists of a sheath of
      cuticular origin surrounding an internal, functional extension of the posterior
      vas deferens. Pedunculate spermatophores were observed within the lumen and
      partially extruding from the terminal opening of the tube in preserved specimens.
      The tube protrudes from the left coxa of the fifth pereopod as an elongate 3-mm
      long, hollow, coiled structure with a terminal opening. Exteriorly the tube
      consists of a conspicuous thick chitinous cuticular ridge throughout its length,
      and a thin chitinous cuticle with sparse, regularly arranged simple setae.
      Interior to the cuticle, the tube contains loose connective tissue, secretory
      cells, oblique muscle, circular muscle, and epithelial cells. The latter cells
      line a central lumen that runs the length of the sexual tube. The morphology,
      cellular composition, and function of the tube are discussed.

PMID- 14666531
TI  - Primatology comes of age: 2002 AAPA Luncheon Address.
AB  - The growth of primate field studies has occurred along multiple dimensions
      representing expansion in the number of species studied, comparative studies of
      different populations of the same species, and populations and groups studied
      over time. The accumulation of data on a broader taxonomic diversity of primates
      has contributed to advances in the use of comparative methods for gaining
      insights into interspecific variation in behavior patterns, but the incorporation
      of intraspecific variation into comparative models of behavior has lagged behind.
      This delay can be attributed, in part, to the slow rate at which the interacting
      effects of life history and demography on behavior emerge in slow-growing, long
      lived primates. It may also reflect the anthropocentric foundation of field
      primatology, which historically focused on interspecific comparisons with humans
      instead of interpopulation variation among primates. Conservation concerns have
      stimulated new thinking about the importance of populations and the range of
      behavioral variation that populations maintain. The integration of intra- and
      interspecific behavioral variation will distinguish the next generation of
      comparative models in primatology, and set a new agenda as field primatology
      comes of age.

PMID- 14666532
TI  - Role of viruses in human evolution.
AB  - The study of viral molecular genetics has produced a considerable body of
      research into the sequences and phylogenetic relationships of human and animal
      viruses. A review of this literature suggests that humans have been afflicted by
      viruses throughout their evolutionary history, although the number and types have
      changed. Some viruses show evidence of long-standing intimate relationship and
      cospeciation with hominids, while others are more recently acquired from other
      species, including African monkeys and apes while our line was evolving in that
      continent, and domesticated animals and rodents since the Neolithic. Viral
      selection for specific resistance polymorphisms is unlikely, but in conjunction
      with other parasites, viruses have probably contributed to selection pressure
      maintaining major histocompatibility complex (MHC) diversity and a strong immune
      response. They may also have played a role in the loss in our lineage of N
      glycolylneuraminic acid (Neu5Gc), a cell-surface receptor for many infectious
      agents. Shared viruses could have affected hominid species diversity both by
      promoting divergence and by weeding out less resistant host populations, while
      viruses carried by humans and other animals migrating out of Africa may have
      contributed to declines in other populations. Endogenous retroviral insertions
      since the divergence between humans and chimpanzees were capable of directly
      affecting hominid evolution through changes in gene expression and development.

PMID- 14666533
TI  - Tooth wear and the "design" of the human dentition: a perspective from
      evolutionary medicine.
AB  - Worn, flat occlusal surfaces and anterior edge-to-edge occlusion are ubiquitous
      among the dentitions of prehistoric humans. The concept of attritional occlusion
      was proposed in the 1950s as a hypothesis to explain these characteristics. The
      main aspects of this hypothesis are: 1) the dentitions of ancient populations in
      heavy-wear environments were continuously and dynamically changing owing to life
      long attritional tooth reduction and compensatory tooth migration, 2) all
      contemporary humans inherit these compensatory mechanisms, and recent reduction
      in wear severity has resulted in failure to develop attritional occlusion, and 3)
      this failure leads to an increased frequency of various dental problems in modern
      societies. Because of the potential significance of this concept, we review and
      synthesize relevant works and discuss attritional occlusion in the light of
      current knowledge. Available evidence, on balance, supports the first and second
      points of the hypothesis. As noted by many workers, the human dentition is
      basically "designed" on the premise that extensive wear will occur, a conclusion
      that seems reasonable when one realizes that humans evolved in heavy-wear
      environments until relatively recently. Some dental problems in contemporary
      societies appear to reflect the disparity between the original design of our
      dentition and our present environment, in which extensive wear no longer occurs,
      but this possibility still needs further investigation.

PMID- 14666534
TI  - Molecular genetic approaches to the study of primate behavior, social
      organization, and reproduction.
AB  - In the past several decades, the development of novel molecular techniques and
      the advent of noninvasive DNA sampling, coupled with the ease and speed with
      which molecular analyses can now be performed, have made it possible for
      primatologists to directly examine the fitness effects of individual behavior and
      to explore how variation in behavior and social systems influences primate
      population genetic structure. This review describes the theoretical connections
      between individual behavior and primate social systems on the one hand and
      population genetic structure on the other, discusses the kinds of molecular
      markers typically employed in genetic studies of primates, and summarizes what
      primatologists have learned from molecular studies over the past few decades
      about dispersal patterns, mating systems, reproductive strategies, and the
      influence of kinship on social behavior. Several important conclusions can be
      drawn from this overview. First, genetic data confirm that, in many species, male
      dominance rank and fitness are positively related, at least over the short term,
      though this relationship need not simply be a reflection of male-male contest
      competition over mates. More importantly, genetic research reveals the
      significance of female choice in determining male reproductive success, and
      documents the efficacy of alternative mating tactics among males. Second, genetic
      data suggest that the presumed importance of kinship in structuring primate
      social relationships needs to be evaluated further, at least for some taxa such
      as chimpanzees in which demographic factors may be more important than
      relatedness. I conclude this paper by offering several suggestions of additional
      ways in which molecular techniques might be employed in behavioral and ecological
      studies of primates (e.g., for conducting "molecular censuses" of unhabituated
      populations, for studying disease and host-parasite interactions, or for tracking
      seed fate in studies of seed dispersal) and by providing a brief introduction to
      the burgeoning field of nonhuman primate behavioral genetics.

PMID- 14666535
TI  - Life history theory and the immune system: steps toward a human ecological
      immunology.
AB  - Within anthropology and human biology, there is growing interest in immune
      function and its importance to the ecology of human health and development.
      Biomedical research currently dominates our understanding of immunology, and this
      paper seeks to highlight the potential contribution of a population-based,
      ecological approach to the study of human immune function. Concepts from life
      history theory are applied to highlight the major challenges and demands that are
      likely to shape immune function in a range of ecological contexts. Immune
      function is a major component of maintenance effort, and since resources are
      limited, trade-offs are expected between investment in maintenance and other
      critical life-history functions involving growth and reproduction. An
      adaptationist, life-history perspective helps make sense of the unusual
      developmental trajectory of immune tissues, and emphasizes that this complex
      system is designed to incorporate information from the surrounding ecology to
      guide its development. As a result, there is substantial population variation in
      immune development and function that is not considered by current biomedical
      approaches. In an attempt to construct a framework for understanding this
      variation, immune development is considered in relation to the competing life
      history demands that define gestation, infancy, childhood, adolescence, and
      adulthood. Each life stage poses a unique set of adaptive challenges, and a
      series of hypotheses is proposed regarding their implications for immune
      development and function. Research in human ecological immunology is in its
      earliest stages, but this is a promising area of exploration, and one in which
      anthropology is well-positioned to make important contributions.

PMID- 14666536
TI  - Natural history of Homo erectus.
AB  - Our view of H. erectus is vastly different today than when Pithecanthropus
      erectus was described in 1894. Since its synonimization into Homo, views of the
      species and its distribution have varied from a single, widely dispersed,
      polytypic species ultimately ancestral to all later Homo, to a derived, regional
      isolate ultimately marginal to later hominin evolution. A revised
      chronostratigraphic framework and recent work bearing either directly or
      indirectly on reconstructions of life-history patterns are reviewed here and,
      together with a review of the cranial and postcranial anatomy of H. erectus, are
      used to generate a natural history of the species. Here I argue that H. erectus
      is a hominin, notable for its increased body size, that originates in the latest
      Pliocene/earliest Pleistocene of Africa and quickly disperses into Western and
      Eastern Asia. It is also an increasingly derived hominin with several regional
      morphs sustained by intermittent isolation, particularly in Southeast Asia. This
      view differs from several current views, most especially that which recognizes
      only a single hominin species in the Pleistocene, H. sapiens, and those which
      would atomize H. erectus into a multiplicity of taxa. Following Jolly ([2001]
      Yrbk Phys Anthropol 44:177-204), the regional morphs of H. erectus may be
      productively viewed as geographically replacing allotaxa, rather than as the
      focus of unresolvable species debates. Such a view allows us to focus on the
      adaptations and biology of local groups, including questions of biogeographic
      isolation and local adaptation. A number of issues remain unresolved, including
      the significance of diversity in size and shape in the early African and Georgian
      records.

PMID- 14666538
TI  - Hunting for health.

PMID- 14666539
TI  - Web hits & misses.

PMID- 14666540
TI  - Artery magic.

PMID- 14666541
TI  - Hey, kids! We've got sugar and toys.

PMID- 14666542
TI  - HealthSouth's most wanted. Founder and former chairman and CEO Richard Scrushy is
      indicted for 85 counts of conspiracy, fraud and money laundering.
AB  - Wake-up call for the industry or an isolated case of corporate chicanery?
      Healthcare experts are divided on the import of Richard Scrushy's indictment on
      85 counts last week in connection with the financial scandal at HealthSouth Corp.
      The indictment alleges the company founder relied on electronic and telephone
      surveillance, threats and intimidation to control his accomplices.

PMID- 14666543
TI  - Quality vs. quantity. IOM report: hospitals must cut back workload and hours of
      nurses to maintain patient safety.

PMID- 14666544
TI  - If you have it, you use it. Latest Blues association study finds new technology
      not only drives demand but also increases spending.

PMID- 14666546
TI  - Giving choice a chance. CMS extends its mandated quality data campaign to include
      home care.

PMID- 14666545
TI  - Quaking in California. Tenet's legal, financial aftershocks keep on coming.

PMID- 14666547
TI  - Final appeal. High court to rule over right to sue for failure to cover doc
      ordered care.

PMID- 14666548
TI  - Putting pricing in the picture. Shielding consumers from true costs of healthcare
      diminishes their responsibility.

PMID- 14666549
TI  - New life for HMOs. Publicly traded Coventry has turned a stable of troubled
      health plans into one of the nation's largest insurers.

PMID- 14666550
TI  - Spine-tingling prospects. Artificial disc implants are among the new technologies
      expected to revolutionize the outcomes of back surgery.

PMID- 14666551
TI  - Medicare at the crossroads: a roundtable discussion on prescription drug
      coverage.

PMID- 14666553
TI  - Desperate measures. As a last resort, more and more obese teens are having their
      stomachs stapled. What are the risks?

PMID- 14666552
TI  - The private Jessica Lynch.

PMID- 14666554
TI  - Drano for the heart. An experimental drug no one expected to work is surprisingly
      effective at rooting out cholesterol.

PMID- 14666555
TI  - Planning way ahead. Long-term-care insurance is a lot cheaper while you're still
      young. Is it a good bet?

PMID- 14666556
TI  - Reborn free?

PMID- 14666557
TI  - Reefer sanity.

PMID- 14666558
TI  - The $44 trillion abyss.

PMID- 14666559
TI  - It takes on the ER (results may vary).

PMID- 14666560
TI  - Winning big in reform bill. After a year of lobbying and much debate, Congress
      reaches a compromise Medicare agreement that pleases providers.
AB  - Providers lobbied hard to get their pet provisions included in the Medicare
      reform legislation, hailed by Sens. John Breaux, left, and Bill Frist. If the
      compromise pact is approved, hospitals and physicians would get more money,
      construction of specialty hospitals would slow, rural providers would get a major
      cash infusion and academic medical centers would be better compensated for their
      teaching costs.

PMID- 14666561
TI  - Do the right thing. New reports show managers must take responsibility for
      creating a culture of safety.

PMID- 14666562
TI  - Overdue update. CMS to use PPS to reimburse psychiatric facilities.

PMID- 14666563
TI  - Won't back down. CMS sticking to inpatient rehabilitation proposal.

PMID- 14666564
TI  - Going back in time. Citing cost efficiency, plans offer narrow networks.

PMID- 14666565
TI  - Change of plans. Keeping trend, Ky. providers shed insurance business.

PMID- 14666566
TI  - Beyond the glitz. Make sure an architectural firm fits your goals before making a
      commitment.

PMID- 14666567
TI  - The art of negotiation. Comparison shopping is essential when choosing a GPO.

PMID- 14666568
TI  - Ready to deal? Managed-care contracting takes research, preparation to really
      work.

PMID- 14666569
TI  - Looking at the big picture. It's important to know what you want technology to
      help your group achieve.

PMID- 14666570
TI  - Letting someone else do it better. Outsourcing business functions can mean higher
      revenue, but not costs.

PMID- 14666571
TI  - Getting in step with integrity pacts. Healthcare providers should try to
      negotiate from a position of strength.

PMID- 14666572
TI  - Homework pays off. Close study of key criteria helps lead to best match in
      physician practice deals.

PMID- 14666573
TI  - Switch pitch. Companies mull when and how to select a different auditing firm.

PMID- 14666574
TI  - Passing the power. Consider executive succession a continuous process, not a
      singular reaction.

PMID- 14666575
TI  - Targeting objectives. Outsourcing saves little money on IT but can help reduce
      wasteful spending.

PMID- 14666576
TI  - Giving the boot. Boards should have plan in place for how to remove a troublesome
      member.

PMID- 14666577
TI  - In need of nurses. Illinois hospital makes name for itself through RN retention,
      recruitment.

PMID- 14666578
TI  - BD makes IT moves. Needle manufacturer adds digital tracking system for mass
      immunizations.

PMID- 14666579
TI  - Straight talk. New approaches in healthcare. Capital financing: beyond the shores
      of your typical transaction.
AB  - If you're in the market to renovate or expand but are concerned about overloading
      your balance sheet with debt or if you plan to build a for-profit facility,
      consider a Design, Build, Finance, and Operate (DBFO) arrangement. In such deals,
      experts in finance, construction, real estate, and support-service provision
      manage risk and day-to-day responsibility for facility management. Evaluating
      alternatives to tax-exempt financing is a critical piece of capital planning
      today because competition for traditional sources of funding has become global.

PMID- 14666580
TI  - Will bigger mean better as AAHP, HIAA merge?

PMID- 14666582
TI  - Malpractice protection efforts seem to come up short.

PMID- 14666581
TI  - Breaking the seal for sake of safety.

PMID- 14666583
TI  - 9 ways to reduce unwarranted variation.

PMID- 14666584
TI  - How broadening DM's focus helped shrink one plan's costs.

PMID- 14666585
TI  - Physician executives need not fly blind. Interview by Patrick Mullen.

PMID- 14666586
TI  - Concierge care by any name raises ethical concerns.

PMID- 14666587
TI  - Case study of a failed merger of hospital systems.
AB  - The failed merger between Geisinger Health System and Hershey Medical Center is
      an instructive case study. The advantages of merging include: 1) support of
      financially threatened academic health centers, 2) access to greater capital, and
      3) integration of managed care principles in the delivery system. Nevertheless,
      if the leadership of the new organization fails to deal effectively with the
      inevitable winners and losers, underestimates the role of cultural differences,
      does not have the management skills necessary to achieve cost savings and address
      the operational inefficiencies resulting from a larger clinical enterprise, does
      not anticipate the distrust of other local health care providers, and fails to
      anticipate the market forces that determine the success or failure of a managed
      health care system, mergers can fail. Lessons to be learned include: mergers
      involving health care systems with competing programs need to plan aggressively
      and execute carefully their clinical consolidation; cultural differences and the
      impediments they cause can be easily underestimated; health system mergers do not
      automatically result in economies of scale; and not all stakeholders in the
      surrounding community necessarily will welcome a merger.

PMID- 14666588
TI  - States exempt psychiatric drugs in some Medicaid programs.

PMID- 14666589
TI  - Making sense of antisense and interference.

PMID- 14666590
TI  - Industry profits seen rising again in 2004.

PMID- 14666591
TI  - Giving lessons.

PMID- 14666592
TI  - Where help is most needed. Demand is up, but some charities are forced to cut
      back services.

PMID- 14666593
TI  - Who's minding the till?

PMID- 14666594
TI  - Strings attached.

PMID- 14666595
TI  - The gatekeeper.

PMID- 14666596
TI  - Importing health hazards.

PMID- 14666597
TI  - Wake up, doc.

PMID- 14666598
TI  - Hey, we're all victims here.

PMID- 14666599
TI  - Trade in the tools of torture. The U.S. government OKs the export of shackles and
      stun guns.

PMID- 14666600
TI  - Forensics. Do bullets tell tales?

PMID- 14666601
TI  - A hard look at what works.

PMID- 14666602
TI  - Relationships 101.

PMID- 14666604
TI  - Bush's cool operator.

PMID- 14666603
TI  - Statin face-off. Surprises from the first head-to-head comparison.

PMID- 14666605
TI  - Alzheimer's in the family.

PMID- 14666606
TI  - Increased CYFRA 21-1 and CEA levels are negative predictors of outcome in p-stage
      I NSCLC.
AB  - Besides established factors, we assessed the prognostic impact of tumor markers
      CYFRA 21-1, CEA and NSE on survival probability in a series of 515 NSCLC patients
      who were treated by surgery. In addition, we studied the prognostic significance
      of CYFRA 21-1 and CEA with reference to the individual postoperative (p-) stages.
      It was found that p-stages correlated inversely with survival probability.
      Complete resection had a favourable impact on prognosis (R0 versus R1/R2: p <
      0.0001). Among patient characteristics, we found that age (> 70 years) was an
      unfavourable prognostic factor (p = 0.0014). Performance status (PS, ECOG) also
      pointed to an adverse prognosis for PS 1-2 versus PS 0 (p = 0.014), whereas
      gender was not prognostically important. Elevated LDH levels (> 240 U/l),
      although non-specific, had adverse prognostic significance (p = 0.0034). Patients
      with CYFRA 21-1 levels above 3.3 ng/ml had a median survival of 24.2 months
      compared to 55.0 months for patients with marker levels below that cut-off point
      (p < 0.0001). CEA levels above 9.8 ng/ml were also associated with shorter
      survival. Median survival was 19.2 months versus 49.9 months in patients with CEA
      levels below 9.8 ng/ml (p < 0.0001). NSE was of no prognostic value. However,
      increased NSE levels (> 14.5 ng/ml) in a subgroup of patients with advanced
      stages IIIa up to IV were found to be associated with shortened survival (p =
      0.024). In p-stage I, 3-year survival was shorter for patients with abnormal
      CYFRA 21-1 levels compared to patients with normal marker expression (60.2%
      versus 78.4%, p = 0.015). CEA was also of prognostic value in this stage (p =
      0.013). In p-stage II, patients with normal CYFRA 21-1 and CEA levels tended to
      have a better outcome (p = 0.064 and 0.09, respectively). Combined use of both
      markers showed that stage I patients in whom both markers were normal had a 3
      year survival rate of 82.5% compared to those where at least one marker was
      abnormal (3-year survival: 55.7%, p = 0.0014). It is concluded that tumor markers
      CYFRA 21-1 and CEA proved to be important adjuncts to the staging system and may
      help to better assess prognosis. A subgroup of p-stage I patients at high risk
      was identified by elevated marker levels. These patients may benefit from
      adjuvant chemotherapy.

PMID- 14666607
TI  - Comparison of serum bone resorption markers in the diagnosis of skeletal
      metastasis.
AB  - BACKGROUND: There are several bone resorption markers which are generated by
      different mechanisms. The serum level of 3 different bone resorption markers in
      cancer patients with or without skeletal metastasis was compared to see whether
      the markers exhibit clinically significant differences useful for metastatic
      screening. PATIENTS AND METHODS: Serum bone metabolic markers were measured in 75
      cancer patients with and 201 cancer patients without skeletal metastasis. The 3
      bone resorption markers, N-terminal cross-linked telopeptide of type I collagen
      (NTx), pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen
      (ICTP) and tartrate-resistant acid phosphatase type 5b (TRAP 5b), and two bone
      formation markers, procollagen type I C-terminal peptide (PICP) and procollagen
      type I N-terminal peptide (PINP), were measured in the single sample. Each marker
      serum level was compared with the menopausal and the osseeous metastatic status
      assessed using Soloway's method for each patient. RESULTS: Bone resorption marker
      serum levels, except for ICTP, were about 16% larger in postmenopausal patients
      than in premenopausal patients. All 3 bone resorption marker serum levels were 3
      4 times greater in patients with extensive skeletal metastasis (extent of disease
      III; EOD = III) than in patients with no osseous metastasis. Although ROC
      analysis indicated each bone resorption marker had a similar sensitivity and
      specificity regarding the ability to detect osseous metastasis, some differences
      were detectable. The T-score of TRAP 5b was elevated, but not significantly so,
      in patients with a small bone metastatic burden (EOD = I). In contrast, although
      the T-score of NTx was not elevated in patients with a small metastatic burden
      (EOD = I), it was significantly elevated in patients with extensive osseous
      metastasis (EOD = III). CONCLUSION: Three bone resorption markers with different
      generation mechanisms showed a difference in menopause and osseous metastasis
      status. The level of ICTP was not elevated in postmenopausal patients, but the
      levels of NTx and TRAP 5b. In osseous metastasis, even though not statistically
      significant, TRAP 5b increased in patients with a small bone metastatic burden
      and NTx increased in patients with extensive bone metastatic burden.

PMID- 14666608
TI  - Canalicular adenoma of the parotid gland: a case report.
AB  - Canalicular adenoma is an uncommon benign neoplasm that occurs almost exclusively
      in the upper lip and, very rarely, in other sites. We describe a case arising in
      the left parotid gland as a firm, painful mass, in order to underline
      morphological and immunohistochemical findings, particularly in relation to
      differential diagnosis with low-grade carcinomas of the salivary glands.

PMID- 14666609
TI  - Merkel cell carcinoma of the head and neck region: report of two cases.
AB  - Two cases of Merkel cell carcinoma (MCC) of the head and neck region are reported
      in order to stress their diversity in morphological, immunohistochemical and
      clinical findings. The remarkable variability of MCC has been analyzed,
      particularly in relation to the differential diagnosis and prognostic
      implications.

PMID- 14666610
TI  - A case of gastric adenocarcinoma associated with giant-cell phlebitis.
AB  - A 60-year-old male patient with advanced gastric adenocarcinoma was treated by
      subtotal gastrectomy with dissection of the regional lymph nodes. Microscopic
      examination of the tumour revealed tubular adenocarcinoma which invaded the
      muscularis propria. There was no evidence of metastatic carcinoma in the
      dissected lymph nodes (pT2N0Mx). Granulomatous reaction comprising epithelioid
      cells and giant cells involved subserosal muscular veins, adjacent to the
      carcinoma tissue. Fibrinoid necrosis, with or without infiltration of
      eosinophils, was noted within the lumen of some veins. The acid-fast and fungal
      stains were negative. Remnants of parasites were not identified in serial
      sections of the paraffin blocks. No pulmonary disease was evident on radiographic
      or pulmonary examination. The presence of granulomatous destruction of muscular
      veins with sparing of arteries suggested the diagnosis of giant-cell phlebitis.
      To our knowledge, there have been no previous reports regarding an association
      between giant-cell phlebitis and advanced gastric adenocarcinoma.

PMID- 14666611
TI  - Laminin-5 gamma 2 chain and matrix metalloproteinase-2 may trigger colorectal
      carcinoma invasiveness through formation of budding tumor cells.
AB  - Tumor budding has been reported to be significantly associated with lymph node or
      distant metastasis in colorectal carcinomas. We attempted to elucidate the
      contributing factors for the formation of budding tumor cells. PATIENTS AND
      METHODS: Fifty T1 colorectal carcinomas were immunostained using several
      antibodies against adhesion-related molecules, and the associations between tumor
      budding and clinicopathological factors were examined. RESULTS: Univariate
      analysis revealed that predominant histology, lymphatic permeation, depth of
      invasion, width of invasion, CD44 variant 6 expression, laminin-5 gamma 2 chain
      expression and stromal MMP-2 expression were associated with tumor budding.
      Multivariate analysis showed that lymphatic permeation, laminin-5 gamma 2 chain
      expression and stromal MMP-2 expression were independently and significantly
      associated with tumor budding. Furthermore, laminin-5 gamma 2 chain and stromal
      MMP-2 expression patterns were significantly associated with locoregional
      failure. CONCLUSION: These results suggest that laminin-5 gamma 2 chain and MMP-2
      may contribute synergistically to the formation of budding tumor cells.

PMID- 14666613
TI  - Flow cytometry expression of p53 and PCNA in oral/oropharynx carcinomas and their
      lymph node metastases.
AB  - The aim of this work was to characterize p53 and PCNA expression in primary
      tumours and lymph node metastases of oral/oropharynx carcinomas by flow cytometry
      and to evaluate the possibility of a relationship between these parameters in
      primary tumours and locoregional metastasis, clinical-histopathological
      parameters and survival time. A group of 28 patients was retrospectively
      selected: 13 with metastasis and 15 without metastasis. The following clinical
      and histopathological parameters were considered: degree of keratinization,
      Broders' grading of histological differentiation, invasive cell grading,
      thickness and tumour size. The nuclei of appropriately prepared cells were
      stained using anti-p53 and anti-PCNA FITC conjugated monoclonal antibodies.
      Analyses were performed by a Coulter Epics Elite flow cytometer. The following
      results were obtained: a close relationship between p53 and PCNA in primary
      tumours but no correlation between them and clinical-histopathological
      parameters; no correlation between p53 and PCNA expression in primary tumours and
      in lymph node metastasis; no correlation between p53 and PCNA values in primary
      tumours and survival. In conclusion, the difference in expression of these
      biological parameters in primary tumours and in lymph node metastases supports
      the theory that tumour cells in lymph nodes can display an independent behaviour.
      Since these biological parameters fail to correlate either with clinical
      histopathological parameters or survival, their prognostic role is questionable.

PMID- 14666612
TI  - Jun activation domain-binding protein 1 expression in malignant lymphoma of the
      thyroid: its linkage to degree of malignancy and p27 expression.
AB  - BACKGROUND: Jab1 (Jun activation domain-binding protein 1) is known as a
      coactivator of the AP1 transcription factor, which contributes to carcinoma
      progression by degrading the p27/Kip1 protein. To date, the clinical significance
      of jab1 in human carcinoma, including malignant lymphoma, has not been studied in
      depth. In this study, we investigated jab1 expression in malignant lymphoma of
      the thyroid. MATERIALS AND METHODS: We immunohistochemically studied jab1
      expression for 50 cases of thyroid lymphoma, as well as 10 cases of chronic
      thyroiditis. RESULTS: Although jab1 was only occasionally expressed in follicular
      cells in normal follicules, it was diffusely positive in those forming small
      follicules typical of chronic thyroiditis and malignant lymphoma. In infiltrating
      lymphocytes in chronic thyroiditis, jab1 was not overexpressed. On the other
      hand, in malignant lymphomas, jab1 overexpression was observed in 24 cases
      (48.0%). It was directly linked to MIB-1 labeling index (p < 0.0001), grade of
      malignancy (p = 0.0130) and aberrant p53 expression (p = 0.0145). Furthermore, an
      inverse relationship was observed between jab1 and p27 overexpression (p =
      0.0130). CONCLUSION: These results suggest that: 1) jab1 plays a role in the
      regenerating of follicular cells attacked by lymphocytes in chronic thyroiditis
      and malignant lymphoma, and 2) jab1 contributes to the progression of malignant
      lymphoma especially with aggressive phenotypes, possibly by degrading p27.

PMID- 14666614
TI  - Prognostic significance of epithelial cells in the blood of patients with
      gynaecological malignancies.
AB  - BACKGROUND: Some studies have shown that the detection of epithelial cells in
      peripheral blood indicates minimal residual disease status. There is a lack of
      data concerning the prognostic relevance of the detection of epithelial cells in
      the blood of patients with solid tumors. Therefore, we conducted the present
      study to analyse the relationship between the detection of epithelial cells in
      the blood, "conventional" prognosis factors and overall survival in patients with
      gynaecological malignancies. MATERIALS AND METHODS: In a prospective study we
      investigated blood samples of patients with benign and malignant gynaecologic
      diseases from 11/97 to 03/99. We used an immunocytochemical approach using
      cytokeratin-directed antibodies CK 8-18 in 135 and A45-B/B3 in another 123
      patients for detection of epithelial cells. Follow-up was obtained by checking
      the local tumor register and contact with all patients included in the study.
      RESULTS: There was no significant correlation between detection rate and tumour
      stage, grading or lymph node status. The median time of follow-up was 45.9 (range
      0.7-63) months. There was no significant correlation between the detection rate
      of positive epithelial cells (method A + B) and overall survival. CONCLUSION: The
      results of this study underline the need to further investigate the role of
      disseminated tumor cells in the blood and bone marrow of patients with
      gynaecological malignancies.

PMID- 14666615
TI  - High-dose carboplatin, cyclophosphamide, etoposide with hematological growth
      factors, without stem cell support in patients with advanced cancer.
AB  - PURPOSE: Peripheral blood progenitor cell (PBPC) transplantation, introduced into
      clinical practice to decrease the hematological toxicity of high-dose
      chemotherapy (HDCT), is both a costly procedure and a potential source of tumor
      cell reinfusion. The maximum tolerated dose of carboplatin (CB), cyclophosphamide
      (CT) and etoposide (VP) administered with growth factors without PBPC was
      determined in a previous phase I study. The aim of this phase II study was to
      evaluate the activity and toxicity of HDCT with CB, CT and VP administered with
      growth factors, without PBPC in a group of patients with advanced solid tumors.
      PATIENTS AND METHODS: Forty patients with a median age of 52 years received two
      consecutive courses of chemotherapy every four weeks, consisting of CT 1500
      mg/m2, VP 400 mg/m2 and CB AUC of 7-8. Following chemotherapy, hematological
      growth factors were administered for 14 days. RESULTS: Grade 4 leukopenia and
      thrombocytemia occurred in 40 and 21 patients, respectively. An overall response
      rate of 72.5% was achieved. After a median 81 months follow-up, median time to
      progression and overall survival were 29 and 38 months, respectively. CONCLUSION:
      These data indicate that HDCT chemotherapy may be delivered safely without PBPC
      support. Prolonged responses were observed in patients that had few therapeutic
      options.

PMID- 14666616
TI  - Peripheral leukocytes with HLA-DR+/CD8- phenotype are associated with prognosis
      in patients with lung cancer.
AB  - BACKGROUND: We have previously reported that the most significant immunological
      prognostic factors in patients with lung cancer are the percentages of peripheral
      HLA-DR+ lymphocytes. PATIENTS AND METHODS: We performed two-color flow cytometric
      analyses using two combinations of double-staining to identify lymphocyte
      phenotypes HLA-DR/CD4 and HLA-DR/CD8, and examined the correlation between the
      expression of these subsets and survival in 51 patients with non-small cell lung
      cancer. RESULTS: The percentages of HLA-DR+, HLA-DR+/CD4+ (activated
      helper/inducer T cells) and HLA-DR+/CD8+ (activated cytotoxic/suppressor T cells)
      did not correlate with survival. However, survival was better when the percentage
      of HLA-DR+/CD8- was below normal (p = 0.0267). The 4-year survival rate in
      patients with high and low percentages of peripheral HLA-DR+/CD8- lymphocytes was
      26.0% and 53.2%, respectively. CONCLUSION: The subset of HLA-DR+/CD8- lymphocytes
      powerfully predicts the survival of patients with non-small cell lung cancer.

PMID- 14666617
TI  - Effects of UFT on thymidylate synthase and dihydropyrimidine dehydrogenase
      activities in lung cancer.
AB  - BACKGROUND: We measured thymidylate synthase (TS) activity, dihydropyrimidine
      dehydrogenase (DPD) activity and TS inhibition rate (TSIR) in tumor tissue and
      lymph node metastasis, considered predictors of response to DIFs, in patients
      with lung cancer. PATIENTS AND METHODS: Fourteen patients with non-small cell
      lung cancer (NSCLC) were given UFT for 1-2 weeks before surgery. Total TS
      activity (total TS), TSIR and DPD activity were measured in tumors, lymph node
      metastases and normal lung and lymph nodes. RESULTS: Total TS activity and DPD
      activity were significantly higher in lung tumors than in normal lung (TS, p =
      0.0225; DPD, p < 0.0001). Total TS activity was slightly but not significantly
      higher in lymph node metastases than in normal lymph nodes. DPD activity and TSIR
      were similar in the other tissues. CONCLUSION: After preoperative treatment with
      UFT, TS and DPD activities are significantly higher in lung tumor tissue than in
      normal lung tissue in patients with NSCLC.

PMID- 14666618
TI  - Survival benefit of stereotactic radiosurgery for metastatic brain tumors in
      patients with controlled primary lesions and no other distant metastases.
AB  - The prognosis of patients with metastatic brain tumors has been very poor so far
      because most patients with metastatic brain tumors had other metastatic lesions
      and/or active primary lesions. Moreover, if no active lesions existed, local
      control of conventional radiation therapy was not so good, which also led to the
      poor prognosis. Thus, we conducted the current study concerning whether survival
      benefit existed in patients with controlled primary lesions and no other distant
      metastases, who were treated with stereotactic radiosurgery (SRS), a superior
      method for local control, for metastatic brain tumors. Seventy-seven patients
      with 90 metastatic brain tumors were treated with SRS between August 1999 and
      August 2001, at Tokyo Metropolitan Komagome Hospital, Japan. Of these, 10
      patients with 17 metastatic brain tumors had primary lesions controlled and no
      other distant metastases were included in the current study. The median
      prescribed isocenter dose was 30 Gy (30-45 Gy) and the median prescribed
      peripheral dose was 25 Gy (12-30 Gy). One-year and 3-year local control rates
      were 90.0% and 90.0%, respectively. One-year and 3-year overall survival rates
      were 88.9% and 51.9%, respectively. These results suggest that SRS for metastatic
      brain tumors does have a survival benefit in patients with controlled primary
      lesions and no other distant metastases, which means that we should not treat
      these patients with palliative intent but pursue longer survival.

PMID- 14666619
TI  - Expression of apolipoprotein A1 in colonic adenocarcinoma.
AB  - In an effort to find proteins overexpressed in metastatic colonic
      adenocarcinomas, differential proteome analyses were undertaken using primary and
      metastatic tumors. Two-dimensional-gel profiles showed a number of spots that
      appeared in metastatic tumor in liver, but not in primary tumor. Amino acid or
      mass spectrometric analyses of some of these spots revealed tht they were
      apolipoprotein A1 (Apo A1), a protein that is normally expressed in liver and
      small intestine. Further RT-PCR analysis verified the expression of Apo A1
      transcript in metastatic tumors and, unexpectedly, expression was also detected
      in the primary tumors, although the expression was weaker than in metastatic
      tumors. Consistent with this finding, immunohistological studies detected the
      weak expression of Apo A1 protein in primary colonic adenocarcinoma, in addition
      to the strong expression in metastatic tumors in liver and lymph nodes. In the
      primary tumors, expression was stronger in the deep layer than in the superficial
      layer, while in normal mucosal epithelial cells expression was barely visible.
      Further immunohistochemical study revealed that Apo A1 is expressed in some
      colonic adenocarcinomas of patients with no metastasis, although incidence and
      expression levels were lower than in carcinomas with metastases. These findings
      are consistent with the notion that expression of Apo A1 is associated with
      colonic adenocarcinoma progression, and thus Apo A1 is a potential marker of the
      aggression.

PMID- 14666620
TI  - Matrix metalloproteinases may contribute compensationally to tumor invasion in T1
      colorectal carcinomas.
AB  - BACKGROUND: Few investigators have focused on possible interactions among several
      MMPs collectively. MATERIALS AND METHODS: Immunostaining for MMP-7, MMP-2 and MT1
      MMP was performed on 51 early invasive (T1) colorectal carcinomas, and
      correlations between the expressions of pairs of MMPs were examined. RESULTS: MMP
      7 expression was positive at the invasive front in 18 (35%) out of 51 tumors.
      Cytoplasmic MMP-2 expression was positive in 20(39%) out of 51 tumors, whereas
      its expression in the stroma was positive in 17(33%) out of 51 tumors. MT1-MMP
      was localized predominantly in the tumor cell cytoplasm in 14 (27%) out of 51
      tumors. There was an inverse correlation between MMP-7 and cytoplasmic MMP-2
      expression with marginal significance (p = 0.06), and between MMP-7 and MT1-MMP
      expression with statistical significance (p = 0.01). The association between
      cytoplasmic MMP-2 and MT1-MMP expression was statistically significant (p =
      0.0004). CONCLUSION: MMP-7 and MMP-2 or MT1-MMP may contribute compensationally
      to tumor invasion and metastasis in T1 colorectal carcinomas.

PMID- 14666621
TI  - Fine-needle aspiration cytology of breast lesions: a review of cytological
      analysis using smooth muscle actin (SMA) immunostaining.
AB  - We reviewed fine-needle aspiration (FNA) cytology cases for breast lesions in
      order to improve the reliability of cytological diagnoses. We analyzed the
      results of 1,019 FNA cytology cases of patients with breast lesions for five
      years in our hospital. One hundred and ninety-seven (19.3%) of the 1,019 cases
      were examined using histological sections, in addition to cytological specimens,
      and included 27 cytologically suspicious cases. Of the 1,019 cytology cases, 606
      (59.5%) were benign, 41 (4.0%) suspicious, 149 (14.6%) malignant and 223 (21.9%)
      inadequate/nondiagnostic. We also performed immunostaining against smooth muscle
      actin (SMA), using 19 cytological specimens and 88 histological specimens. We
      observed myoepithelial cells positive for SMA, which were valuable for
      cytological or histological diagnosis. To improve the reliability of cytological
      diagnoses and decrease the false-positive and false-negative cases, it is very
      important to obtain sufficient aspirates and to understand the cytological
      characteristics of various benign and malignant breast lesions.

PMID- 14666622
TI  - Implication of extended lymph node dissection stratified for advanced gastric
      cancer.
AB  - BACKGROUND: What extent of lymph node dissection for advanced gastric cancer is
      appropriate is a matter of controversy. PATIENTS AND METHODS: Three hundred and
      ninety-nine gastric cancer patients underwent potentially curative D2 gastrectomy
      and 125 underwent D3 gastrectomy between 1985 and 1998. RESULTS: Our study
      revealed that pN3, but not D3 gastrectomy, significantly influenced prognosis.
      There was no significant difference in the 5-year survival rate and mean survival
      time between D2 and D3 patients: but the survival in D3 patients with tumor
      diameters measuring 50-100 mm or with pN1 was significantly longer than that in
      D2 patients with the same tumors. Analysis of survival of patients with tumor
      diameters measuring 50-100 mm revealed that there was a significant difference
      only in pN1. The incidence of lymphatic recurrence was significantly lower in D3
      patients with pN1 tumor or a tumor measuring 50-100 mm than in D2 patients.
      CONCLUSION: Patients with advanced gastric cancer measuring 50-100 mm and pN1 may
      benefit from para-aortic lymph node dissection.

PMID- 14666623
TI  - Gingival metastasis as initial presentation of small cell carcinoma of the lung.
AB  - We describe an 84-year-old man with small cell carcinoma of the lung (SCLC)
      initially manifesting as gingival metastasis. Although SCLC is well known for
      early and widespread dissemination, metastasis to the gingiva is extremely rare.
      We know of only two case reports describing gingival metastasis from SCLC and in
      these cases gingival metastasis was not the presenting occurrence. Physicians
      should be aware that, on rare occasions, gingival metastases can be the
      presenting event in SCLC.

PMID- 14666624
TI  - Outcome of patients with hepatitis C virus-related single, small hepatocellular
      carcinoma.
AB  - To clarify the cumulative recurrence-free interval and survival rate with
      hepatitis C virus (HCV)-related single, small hepatocellular carcinoma (HCC), we
      studied 32 patients with surgical resection, 61 with ablation therapy and 28 with
      transcatheter chemoembolization (TACE). A log-rank test revealed that there were
      no significant differences in the recurrence-free interval (p = 0.08) and
      survival (p = 0.279) between the resection and the ablation groups. Univariate
      analysis using the Cox proportional hazards regression model showed initial
      treatment (p = 0.0051) was associated with recurrence-free interval. Platelet
      count (p = 0.009), indocianine green retention rate at 15 minutes (p = 0.003),
      Child-Pugh classification (p = 0.001), serum albumin level (p = 0.0012) and serum
      total bililubin (p = 0.015) were associated with survival. Hence patients with
      HCV-related single, small HCC should be treated according to their hepatic
      reserve.

PMID- 14666625
TI  - Case report: case of clear cell sarcoma surviving with the primary lesion for 20
      years after resection of a metastatic lymph node.
AB  - In this paper we report on an extremely rare case of clear cell sarcoma, which is
      a rare malignant soft tissue tumor, biologically similar to malignant melanoma.
      The patient has survived for 25 years after he noticed a small tumor mass at the
      wrist and for 20 years after a small sentinel lymph node metastasis in the axilla
      was removed by surgical resection. The patient visited us because the tumor in
      his wrist had increased rapidly in size during the previous year. We diagnosed
      the wrist tumor as a clear cell sarcoma, based on the typical histopathological
      findings and positivity of the tumor cells for HMB-45 and S-100 protein; the
      histopathological findings in the axillary soft tissue tumor resected 20 years
      previously were also compatible with clear cell sarcoma of the lymph node.
      Therefore, we concluded that the wrist tumor was the primary lesion of clear cell
      sarcoma and that the axillary tumor was a metastatic lesion in a sentinel lymph
      node. Generally, the prognosis of clear cell sarcoma is very poor, especially
      after the occurrence of lymph node metastasis. In this case, it is possible that
      certain immune mechanisms played a role in effectively suppressing the tumor
      growth for such a prolonged period, even after the development of lymph node
      metastasis.

PMID- 14666626
TI  - Irinotecan and gemcitabine in patients with advanced non-small cell lung cancer,
      previously treated with cisplatin-based chemotherapy. A phase II study.
AB  - BACKGROUND: To evaluate the efficacy and tolerability of irinotecan plus
      gemcitabine administered every two weeks in patients with advanced non-small cell
      lung cancer (NSCLC) previously treated with cisplatin-based chemotherapy.
      PATIENTS AND METHODS: Fifty patients with advanced NSCLC, refractory or resistant
      to cisplatin derivatives, were treated on an out-patient basis with irinotecan
      150 mg/m2 intravenously (i.v.) and gemcitabine 1,800 mg/m2 i.v. on days 1 and 15,
      every two weeks. The response to treatment was evaluated every two cycles. The
      patients' median age was 59 years, 44 were men and 92% had a performance status
      (PS) of 0-1. RESULTS: On an intent-to-treat analysis, 8 (16%) patients, [95%
      confidence interval (CI), 7.2% to 29.1%] achieved partial response (PR), 19 (38%)
      stable disease (SD) and 23 (46%) progressive disease (PD). The median time to
      tumor progression (TTP) was 5.5 months (range, 0.1 to 16.5 months), the median
      survival time was 8.1 months (range, 0.8 to 22.1 months) and the 1-year survival
      36% (95% CI, 22.9% to 50.8%). Clinical benefit response, including improvement of
      PS, dyspnea, anorexia and fatigue, cessation of hemoptysis and fever and
      reduction of cough and pain, was observed in 10% to 44% of patients. No patient
      experienced grade 3/4 anemia. Grade 3/4 neutropenia and thrombocytopenia occurred
      in 7 (14%) and 8 (16%) patients, respectively. Five (10%) patients were
      hospitalized due to febrile neutropenia and were successfully treated with broad
      spectrum antibiotics and G-CSF support. One (2%) patient experienced grade 4
      fatigue and discontinued treatment. Other grade 3/4 adverse events included
      diarrhea (3 cases, 2 of whom required hospitalization), alopecia (5 cases),
      asthenia (2 cases) and allergy (2 cases). Eight (16%) patients required a dose
      reduction. There were no treatment-related deaths. CONCLUSION: The combination of
      irinotecan and gemcitabine, administered every two weeks, demonstrated rather
      modest activity in advanced NSCLC patients who had previously been treated with
      cisplatin-based chemotherapy. It was well tolerated with mild toxicity and was
      associated with significant 1-year survival rate and symptomatic benefit
      response.

PMID- 14666627
TI  - Her-2/neu oncogene amplification and protein over-expression in interval and
      screen-detected breast cancers.
AB  - BACKGROUND: Studies of Her-2/neu protein expression in interval and screen
      detected breast cancers have been conflicting. Therefore we assessed the Her
      2/neu amplification status in these groups by using in situ hybridization.
      PATIENTS AND METHODS: The Her-2/neu oncogene amplification and protein over
      expression were compared in 79 screen-detected and 39 interval breast carcinomas,
      using a novel and well-documented chromogenic in situ hybridization (CISH) method
      and immuhistochemistry. RESULTS: There were 33% CISH-positive cases in the
      interval cancer group and only 4% CISH-positive cases in the screen-detected
      group. The odds ratio for interval cancer was 14.1 (95% CI 2.2 to 91.0) in the
      CISH-positive tumours compared with CISH-negative tumours after adjustment for
      nodal status, tumour size and histological grade. CONCLUSION: Our results
      indicate, for the first time, that there is a clear-cut difference in Her-2/neu
      amplification between screen-detected and interval breast carcinomas. The
      amplification appears to be a rare event in screen-detected cancers but
      distinctly frequent in interval cancers when compared to cancers described in
      earlier studies.

PMID- 14666628
TI  - Docetaxel as salvage therapy in advanced gastric cancer: a phase II study of the
      Gruppo Oncologico Italia Meridionale (G.O.I.M.).
AB  - BACKGROUND: Docetaxel (DCT), a semisynthetic taxoid, has demonstrated cytotoxic
      activity against gastric cancer in early phase II studies producing an overall
      response rate of 17-24%. The Gruppo Oncologico Italia Meridionale (G.O.I.M.)
      started a confirmatory multicenter phase II trial to evaluate the clinical
      activity and toxicity of single agent TXT in the treatment of advanced gastric
      cancer patients who had failed a first-line chemotherapy. MATERIALS AND METHODS:
      Thirty patients with advanced gastric carcinoma refractory to first-line ECF or
      PELF chemotherapy were treated with DCT administered at the dosage of 100 mg/mq
      given as a 1-hour i.v. infusion every three weeks. All patients received a
      premedication with dexamethasone 8 mg i.v. 12 hours and 1 hour before, and 12
      hours after DCT administration. Granulocyte colony stimulating factor was
      employed in case of febrile neutropenia as needed. The first evaluation of
      disease status was planned after three cycles. RESULTS: We observed 5 partial
      responses without any complete response for an overall response rate of 17% (95%
      CI = 6-36%, intent-to-treat analysis). Nine patients showed stable disease and 14
      patients progressed. The duration of objective partial responses were 5, 6, 6, 9
      and 12 months, respectively. The median overall survival was 6 months and the 1
      year survival rate was 20.6%. No chemotherapy-related toxic death was observed.
      Haematological grade 3-4 side-effects were respectively: anemia (7%), leucopenia
      (7%) and neutropenia (18%); in 13 patients (45%) G-CSF was employed to avoid
      severe leukopenia. CONCLUSION: This multinstitutional single-step phase II study
      confirms that single-agent docetaxel is active in advanced gastric cancer
      progressing after first-line chemotherapy. The most frequent toxicity is
      neutropenia, which may be managed by G-CSF and/or dose adjustments. Docetaxel is
      therefore worthy of further study in combination with other active drugs.

PMID- 14666629
TI  - The combination of multi-voxel MR spectroscopy with MR imaging improve the
      diagnostic accuracy for localization of prostate cancer.
AB  - BACKGROUND: We assessed the usefulness of combined multi-voxel magnetic resonance
      spectroscopy (MRS) and MR imaging (MRI) in the diagnosis of prostate cancer
      localization. PATIENTS AND METHODS: MRS and MRI were performed in 21 patients
      with prostate cancer. On T2-weighted images, tumor localization was based on low
      signal intensity in the peripheral zone. At MRS, cancer patterns were diagnosed
      when the ratio of choline plus creatine to citrate was greater than 0.86. The
      results were analyzed with reference to pathological confirmation of prostate
      cancer at bilateral or unilateral lobe. RESULTS: Six out of 11 patients with
      unilateral positive biopsy specimens were diagnosed as unilateral cancer, and 9
      of 10 patients with bilateral positive biopsy specimens were diagnosed as
      bilateral cancer on MRI. Two of 4 patients with unilateral cancer, who were not
      detected on MRI alone, were diagnosed as unilateral cancer on combined MRI and
      MRS. The accuracy of MRI alone was 71.4%, while that of combined MRI and MRS was
      81.0%. CONCLUSION: Combined MRI and MRS improved the diagnostic accuracy for
      localization of prostate cancer.

PMID- 14666630
TI  - Multicyclic dose-intensive chemotherapy supported by autologous blood progenitor
      cell transplantation for relapsed small cell lung cancer.
AB  - We report two cases with small cell lung cancer (SCLC) receiving multicyclic dose
      intensified chemotherapy (DI-CT) supported by autologous blood progenitor cell
      transplantation (ABPCT). Both cases were initially treated with cisplatin (CDDP),
      etoposide (ETP) and concurrent thoracic irradiation, however they had recurrent
      disease within a year. After receiving conventional chemotherapy, they underwent
      multicyclic DI-CT consisting of CDDP, ETP and ifosfamide supported by G-CSF and
      ABPCT. Definite regression of the tumors was observed. Severe neutropenia and
      thrombocytopenia were encountered but they were reversible and no life
      threatening complications were experienced. These results suggest the feasibility
      and effectiveness of multicyclic DI-CT and the usefulness of ABPCT as a treatment
      option for relapsed SCLC.

PMID- 14666631
TI  - Recurrent dermatofibrosarcoma protuberans sixteen years after radical excition. A
      case report.
AB  - We report the case of a young patient with an apparently benign slowly growing
      lesion which was excised 15 years after its occurrence. However, the
      histopathological examination revealed a DFSP which necessitated two more
      surgical procedures for inadequate surgical margins and a skin graft.
      Notwithstanding these radical operations, the patient presented a local
      recurrence 16 years later, suggesting that the insidious behavior of the tumour
      must be taken into account and that patients with DFSP need a life-long follow
      up.

PMID- 14666632
TI  - Comparison of FDG-PET and technetium-99m MIBI SPECT to detect metastatic cervical
      lymph nodes in well-differentiated thyroid carcinoma with elevated serum HTG but
      negative I-131 whole body scan.
AB  - The aim of this study was to evaluate the usefulness of 18-fluoro-2-deoxyglucose
      (FDG) positron emission tomography (PET) and technetium-99m
      methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed
      tomography (SPECT) in detecting metastatic cervical lymph nodes (LN) in well
      differentiated thyroid carcinoma (DTC) after total thyroidectomy and radioiodine
      131 (I-131) treatments in patients with elevated serum human thyroglobulin (hTg)
      levels but negative I-131 whole body scan (WBS). Fifteen DTC patients underwent
      nearly total thyroidectomy and I-131 treatments with cervical LN metastases were
      included in this study. All subjects had negative I-131 WBS and elevated hTg
      levels (hTg > or = 10 microIU/ml) under thyroid-stimulating hormone (TSH)
      stimulation (TSH > or = 30 microIU/ml). FDG-PET could detect all of the 15 (100%)
      patients with metastatic cervical LN, but Tc-99m MIBI SPECT revealed lesions in
      only 9 out of 15 (60%) patients (p value < 0.05). This study demonstrated that
      FDG-PET is more sensitive than Tc-99m MIBI SPECT in detecting metastatic cervical
      LN in DTC with elevated serum hTg levels but negative I-131 WBS.

PMID- 14666633
TI  - Two cycles of carboplatin-based adjuvant chemotherapy for high-risk clinical
      stage I and stage IM non-seminomatous germ cell tumours of the testis: a HECOG
      trial.
AB  - BACKGROUND: We investigated the efficacy and safety of 2 cycles of adjuvant
      chemotherapy with carboplatin, etoposide and bleomycin (CEB90) in patients with
      high-risk clinical stage I or stage IM non-seminomatous germ cell tumours
      (NSGCT). PATIENTS AND METHODS: A total of 52 consecutive patients (22 patients
      with high-risk histological features [vascular invasion, presence of embryonal
      carcinoma, absence of yolk sac tumour] and 30 with tumour marker activity post
      orchidectomy-stage IM) were entered into this prospective study. Chemotherapy
      consisted of carboplatin 400 mg/m2 or AUC 5 (day 1), etoposide 165 mg/m2 (days 1
      3) and bleomycin 30 mg (days 1, 8, 15). Chemotherapy was repeated every 3 weeks.
      RESULTS: During a median follow-up of 112 months (range, 10 to 174 months), two
      patietns with stage IM relapsed. These cases had a disseminated, marker-positive
      germ cell tumour (GCT), extensively involving both liver and lungs in the first
      case and para-aortic lymph nodes and lung in the second one; both patients died
      of the tumour after a number of salvage chemotherapy (including high-dose
      therapy) regimens. Fifty patients (96%) are alive and disease-free. Two cycles of
      CEB90 were well tolerated and the only side-effects were myelotoxicity and
      alopecia. CONCLUSION: Despite the general consensus that ciplatin-based
      chemotherapy is superior to carboplatin-containing regimens in testicular cancer,
      2 cycles of CEB90 may be an equally effective treatment option as adjuvant
      therapy for high-risk clinical stage I and IM patients.

PMID- 14666634
TI  - Liver metastases of colorectal cancer: medical treatments.
AB  - Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the
      Western world. Liver metastases form the main cause of death in patients with
      colorectal cancer. Already at the time of the primary tumor, 15-25% of the
      patients present with liver metastases, while another 20% will develop these
      metastases following treatment of the colorectal primary. Without any treatment
      the median survival after the detection of liver metastases is approximately 9
      months, depending on the extent of the disease at the time of diagnosis. This
      paper examines the factors pertinent to clinical trial designed for metastic
      colorectal cancer and reviews the existing data supporting adjuvant and
      neoadjuvant therapy for potentially resectable disease and chemotherapy in the
      inoperable disease.

PMID- 14666635
TI  - Lack of association between CCND1 G870A polymorphism and the risk of breast and
      colorectal cancers.
AB  - BACKGROUND: The aim of this case-control study was to investigate whether the
      common G870A polymorphism in the Cyclin D1 gene (CCND1) is a risk factor for
      breast and colorectal cancers in an Australian population. PATIENTS AND METHODS:
      A total of 339 breast and 569 colorectal cancer cases were studied, together with
      327 age-matched controls. Genotyping for the G870A polymorphism in CCND1 was
      carried out using single strand conformation polymorphism and Pyrosequencing
      methods. RESULTS: Comparison of the CCND1 G870A genotype frequencies revealed no
      significant associations between presence of the A allele and the risk of either
      breast or colorectal cancer. No associations were noted between presence of the A
      allele and pathological features of these tumours or patient survival.
      CONCLUSION: Although the CCND1 G870A polymorphism has been reported as a genetic
      risk factor for some tumour types, it does not appear to be linked to the risk of
      breast and colorectal cancers.

PMID- 14666636
TI  - Association between fibronectin expression and prognosis in ovarian carcinoma.
AB  - BACKGROUND: Fibronectin is involved in tumour neovascularisation and metastasis,
      prevents apoptosis and is considered to be immunosuppressive. This study aimed to
      determine the prognostic value of fibronectin expression in ovarian carcinoma.
      MATERIALS AND METHODS: Records and archival tumour tissue from 211 German women
      with ovarian carcinoma were reviewed. Total fibronectin was determined
      immunohistochemically (clone N-294). Univariate and residual Kaplan-Meier
      survival analysis were used to correlate fibronectin expression with established
      prognostic indicators and overall survival. RESULTS: Fibronectin expression
      correlated significantly with tumour stage (p = 0.002) and tumour growth fraction
      (p = 0.005). The degree of expression had a significant adverse influence on
      overall survival even after other prognostic factors had been excluded (p =
      0.009). CONCLUSION: Fibronectin is an important prognostic factor in ovarian
      cancer and may be central to tumour progression. These findings offer new
      treatment possibilities since several agents may antagonise the mechanism of
      fibronectin expression.

PMID- 14666637
TI  - TV-image analysis based quantification of the proliferative activity and the
      apoptotic rate in thyroid tumors and thyroiditis.
AB  - To analyze the impact of cellular proliferative activity and apoptosis, MIB-1
      immunopositivity and the apoptotic rate of normal tissue (n = 20), follicular
      adenoma (n = 30), follicular carcinoma (n = 32), papillary carcinoma (n = 40),
      Hashimoto thyroiditis (n = 17) and de Quervain thyroiditis (n = 12) was
      investigated by means of TV-image analysis. Three-micron sections from paraffin
      embedded surgical specimens were investigated. Immunohistochemical reactions were
      performed using an indirect peroxidase method. For determination of apoptosis the
      in situ DNA nick-end labeling method (TUNEL) was used. The rate of positive cells
      was determined using the CM-2 TV-image analysis system (Hund, Wetzlar, Federal
      Republic of Germany). Forty viewing fields (1.94 mm2) were measured with 20:1
      objective mangnification. An average of > 4,400 cells were assessed in each case.
      The mean MIB-1 immunopositivity was higher in follicular carcinoma (average,
      2.30%) than in de Quervain thyroiditis (1.48%), papillary carcinoma (1.26%),
      Hashimoto thyroiditis (0.97%), follicular adenoma (0.58%) and normal thyroid
      tissue (0.14%). The apoptotic rates were higher in Hashimoto thyroiditis (4.54%)
      and de Quervain thyroiditis (3.55%) than in thyroid tumors (0.31%-0.49%) and
      normal thyroid tissue (0.10%). Calculating the ratio of MIB-1 expression and
      apoptotic rate, thyroid tumors (12.1-14.6) revealed higher values than normal
      thyroid tissue (3.6), indicating cell gain. In Hashimoto thyroiditis (1.7) and de
      Quervain thyroiditis (0.7) the ratio was lower than in normal tissue indicating
      cell loss. MIB-1 immunohistometry and apoptotic rate quantification present new
      insights into the proliferative and apoptotic potential of thyroid lesions based
      on a high number of cells investigated per case. The impact of both methods could
      be used for the interpretation of diagnostically difficult and inconclusive fine
      needle aspirates. However, as there was an overlap of the single values, the
      results have to be interpreted carefully for diagnostic purposes.

PMID- 14666638
TI  - Tumor markers as prognostic factors in treated non-small cell lung cancer.
AB  - The usefulness of tumor markers in non-small cell lung carcinoma (NSCLC) is not
      well defined. The aim of this study was to determine the predictive value for
      response to treatment and prognosis of pretreatment concentrations of tumor
      markers. The pretreatment levels of CEA, CA125 and CYFRA21-1 were determined by
      electrochemoluminiscence in 48 patients with advanced stage (IIIA-IV) NSCLC
      treated with platin-based chemotherapy. The sensitivity for CYFRA21-1, CA125 and
      CEA was 66.7%, 45.8% and 47.3%, respectively. The predictive factors for non
      response to treatment were CA125 > 35 KU/L (OR = 5.36; p = 0.017) and presence of
      metastasis (OR = 6.92; p = 0.007). The prognostic factors for survival were
      Performance Status > 1 (HR = 4.22; p = 0.0002), presence of metastasis (HR = 3.1;
      p = 0.0028) and CA125 > 35 KU/L (HR = 2.33; p = 0.02). In conclusion, CA125 is a
      predictive factor for response to treatment and a prognostic factor for survival
      in patients with NSCLC treated with chemotherapy.

PMID- 14666639
TI  - AMES, MACIS and TNM prognostic classifications in papillary thyroid carcinoma.
AB  - The need for total thyroidectomy and extended for lymphadenectomy and the need
      for postoperative radioiodine ablation in the treatment of papillary thyroid
      carcinoma is continuously debated. Since less aggressive treatment in low-risk
      patients has been suggested, several scoring systems have been developed to
      identify low-risk patients. In the current study, we compared the AMES, MACIS and
      TNM staging systems in predicting carcinoma-specific mortality in papillary
      thyroid carcinoma. Between 1967 and 1994, 495 patients with papillary thyroid
      carcinoma were treated at the Department of Surgery, Helsinki University Central
      Hospital. Carcinoma-specific mortality in the AMES low-risk group, comprising
      89.7% of these patients, was 2.4%. Corresponding figures for the MACIS were
      89.9%, and 2.4%, and for the TNM 85.9% and 1.2%. The mortality ratio, at 10
      years, between low-risk and high-risk patients was 22.2 for the AMES, 25.0 for
      the MACIS and 41.8 for the TNM system. The proportion of explained variance in
      the Cox model was 16.3 for the AMES, 30.0 for the MACIS taken as a conitinuous
      variable and 28.9 for the TNM stage. The TNM stage was on average superior to the
      MACIS or AMES score in predicting cancer-specific mortality of patients with
      papillary thyroid carcinoma. This may be explained by the fact that the TNM
      system includes the prognostic effect of nodal metastases, which is included in
      neither the MACIS nor AMES systems.

PMID- 14666640
TI  - Human papilloma virus typing at large loop excision of the transformation zone of
      the cervix uteri.
AB  - BACKGROUND: The aim of this study was to evaluate whether human papilloma virus
      (HPV) testing at LLETZ for CIN can be useful to identify patients with high risk
      of recurrent disease. MATERIALS AND METHODS: In 62 women treated with LLETZ for
      CIN the status of the resection margins was recorded and related to the HPV
      status as assessed with Hybrid Capture II immediately after surgery. A control
      typing was repeated 3-9 months later. In all cases, a ThinPrep thinlayer cytology
      was further performed. RESULTS: In 19 of the 62 surgical specimens (30.6%) the
      resection margin was positive for dysplasia or dysplastic epithelium was close (<
      0.5 mm) to the margin (RM+), while in 43 cases (69.4%) the margins were negative
      (RM-). At surgery, 21 out of 62 cases (33.9%) were HPV+ (47.4% RM+, 27.9% RM-)
      and 13 turned HPV- at the control typing. From the 41 out of 62 (66.1%) initially
      HPV-cases, 12 turned into HPV+. Cytological follow-up was abnormal (ASC+) in 65%
      HPV+ cases, whereas all HPV- were WNL. CONCLUSION: Post-operative HPV testing
      with HC-II is well-suited to detecting women with residual HPV infection, even in
      cases with negative surgical margins. Furthermore, HPV testing at surgery could
      replace endocervical curettage and help in distinguishing true residual disease
      from reinfections.

PMID- 14666641
TI  - Dendritic cell-based vaccines in breast and gynaecologic cancer.
AB  - Major advances in understanding the functional interactions between tumour cells
      and the host immune system, in particular the generation and regulation of T cell
      immunity, have revived interest in cancer vaccination strategies. A crucial step
      for mounting an anti-tumour response is the capture, processing and presentation
      of tumour antigens (TA) to cognate T cells by professional antigen-presenting
      cells (APC), followed by their activation and clonal proliferation. Dendritic
      cells (DC) are potent APC with the unique ability to stimulate primary immune
      responses. Animal models have demonstrated that TA-charged DC can activate
      specific cytotoxic T cells (CTL) and even regression of established tumours in
      cancer-bearing hosts. These findings, as well as the elaboration of methods for
      generating large numbers of DC ex vivo, have provided a compelling rationale for
      using DC as potent adjuvants to deliver TA to the immune system in order to
      trigger or amplify an inadequate response. The capacity of TA-pulsed DC to induce
      significant CTL immunity translating into occasional therapeutic benefit has been
      documented in several clinical settings including B cell lymphoma, myeloma,
      melanoma, prostate, colon, ovarian and renal cell carcinoma. In this review, we
      summarize key biological functions of DC and focus on recent DC-based vaccination
      trials of breast, ovarian and cervical cancer.

PMID- 14666642
TI  - Expression of stem cell factor and lack of c-kit expression in malignant fibrous
      histiocytoma of soft tissues.
AB  - BACKGROUND: Little information is available on the expression of stem cell factor
      (SCF) and its receptor c-kit in soft tissue tumors of a fibrohistiocytic origin,
      including malignant fibrous histiocytoma (MFH). MATERIALS AND METHODS: We
      investigated the endogenous expression of SCF and c-kit in 43 MFH tissue samples
      using immunohistochemical techniques. Furthermore, we examined the correlation of
      SCF expression in MFHs with proliferative activity assessed by mitotic indices
      and MIB-1 immunohistochemical staining. RESULTS: Positive immunoreactivity for c
      kit was identified in tumor cells of only one MFH case, while the remaining 42
      cases were negative. In the one positive case, immunohistochemical staining was
      focal. Positive immunoreactivity for SCF was identified in 31 out of 43 cases
      studied (72%, focal; 11, moderate; 6, diffuse; 14). There were no significant
      differences in the MIB-1 and mitotic indices between the SCF-positive and
      negative groups. CONCLUSION: Our data indicate that any direct autocrine effects
      of the SCF/c-kit system on cell growth regulation are precluded in most MFH cases
      studied, but it is speculated that SCF might indirectly influence tumor growth by
      promoting local neovascularization.

PMID- 14666643
TI  - Superoxide-dismutase activity of the gastric mucosa in patients with Helicobacter
      pylori infection.
AB  - BACKGROUND: Helicobacter pylori (HP) is a pathogenic factor in the development of
      different alterations in the gastric mucosa. Superoxide-dismutase (SOD) is a key
      enzyme of mucosal antioxidant protection. We have detected changes in the
      activity of mucosal SOD in different diseases caused by HP. MATERIALS AND
      METHODS: Biopsies were taken upon gastroscopy (n = 131). Activity of SOD was
      measured by photometry, referred to the amount of protein in the sample. RESULTS:
      SOD activity of the antrum of HP-positive patients was significantly higher than
      that of HP-negative ones. There was a significant increase in erosive gastritis.
      CONCLUSION: In the presence of HP there was a significant increase of the SOD
      activity in the antrum but not in the corpus. In chronic antral gastritis there
      was a positive relationship between the SOD activity and both the severity and
      activity of inflammation. We presume that HP-associated gastritis is predominant
      in the antrum.

PMID- 14666644
TI  - Adenocarcinoma in inflammatory colorectal disease. Histological features
      pertinent to local tumour progression.
AB  - Histological sections of 65 surgical specimens from patients with inflammatory
      colonic disease (ICD) and a colorectal carcinoma, were reviewed. Twenty-five
      specimens had ulcerative colitis, 35 Crohn's colitis and 2 indeterminate colitis.
      The presence of neoplastic glands at the tumour front having: a) retained mucin,
      inflammatory cells and/or necrotic material, b) neoplastic glands with a thin
      layer of tumour cells, c) neoplastic glands lacking a group of tumour cells (i.e.
      glandular pore formation) and d) neoplastic glands in which the intraglandular
      retained mucin, inflammatory cells and/or necrotic material were seen discharged
      through the glandular pores into the juxtaposed matrix, were recorded. Of the 58
      specimens with gland-forming adenocarcinomas, 17 (29.3%) had at the invading
      front neoplastic glands with a thin layer of tumour cells and 56 (96.6%)
      neoplastic glands with pores. The material discharged through those pores into
      the surrounding matrix was mucin (n = 46), inflammatory cells -mainly
      granulocytes- and/or necrotic material (n = 10). It was assumed that the thin
      layer of tumour cells in neoplastic glands antedated glandular "pore" formation.
      Through those "pores" mucin, inflammatory cells and/or necrotic material were
      subsequently released into the surrounding host tissues. Those products, rich in
      proteolytic enzymes, would encourage the degradation of the juxtaposed normal
      tissues, thus facilitating local tumour growth. To restore the continuity of
      those incomplete glands, new cancer cells would grow around mucin "lakes" or
      inflammatory-necrotic aggregates in the stroma. This mechanism will guarantee a
      life-long tumour progression in untreated patients.

PMID- 14666645
TI  - Micrometastases in axillary lymph nodes and bone marrow of lymph node-negative
      breast cancer patients--prognostic relevance after 10 years.
AB  - The long-term prognostic significance of immunohistochemically detectable occult
      tumor cells in bone marrow and axillary lymph nodes of breast cancer patients
      considered to be lymph node-negative in multilevel haematoxylineosin (H&E) lymph
      node sectioning was analyzed. A total of 212 patients with a median follow-up of
      10.3 years were included in the study. Bone marrow was obtained during surgery
      and stained with anti-cytokeratin and anti-EMA antibodies. Additional consecutive
      sections of lymph nodes were stained either with H&E or with anti-cytokeratin
      antibodies. All histological sections were analyzed by the same pathologist.
      Micrometastases were detected in bone marrow of 67 (32%) patients.
      Immunohitochemical examination of negative axillary lymph nodes--based on
      multilevel H&E examination--revealed micrometastases in 14 (7%) cases. There was
      no difference in overall or disease-free survival between patients with or
      without epithelial cells in bone marrow. Immunohistological examination of
      axillary lymph nodes also did not add any prognostic information for overall or
      disease-free survival. However, patients with occult micrometastases in axillary
      lymph nodes had a slightly higher rate of local recurrences. Immunohistochemical
      analysis of bone marrow or axillary lymph nodes does not add prognostic
      information if multilevel H&E sectioning is performed. Therefore, decision about
      adjuvant therapy in breast cancer patients considered to be lymph node-negative
      in multilevel H&E microscopy should not be based on immunohistochemical detection
      of micrometastases in bone marrow or axillary lymph nodes.

PMID- 14666646
TI  - Immunohistochemical analysis of platelet-derived growth factor and its receptors
      in soft tissue malignant fibrous histiocytoma.
AB  - BACKGROUND: Little information is available regarding the expression of platelet
      derived growth factor (PDGF) isoforms and their receptors in soft tissue
      malignant fibrous histiocytoma (MFH). MATERIALS AND METHODS: We investigated
      expression of PDGF isoforms and their receptors (PDGF-R alpha and -R beta) in 43
      MFH tissue specimens using immunohistochemical techniques. Furthermore, we
      examined the correlation of PDGF expression in MFHs with proliferative activity
      assessed by MIB-1 immunohistochemical staining. RESULTS: Positive cytoplasmic
      immunoreactivity for PDGF-AA, -BB and -AB was identified in tumor cells of 28
      (66%), 4 (10%) and 26 (61%), respectively, of the 43 MFHs analyzed. Positive
      cytoplasmic immunoreactivity for PDGF-R alpha and -R beta was identified in tumor
      cells of 41 (95%) and 32 (74%), respectively, of the MFHs. Thirty-four (79%) MFHs
      coexpressed one or more PDGF isoforms and their corresponding receptors. In PDGF
      AA immunostaining, MIB-indices in the high immunoreactivity group (> 10% of tumor
      cells) were significantly higher than those in the low immunoreactivity group (<
      10% of tumor cells) (p = 0.031). CONCLUSION: Our data provide evidence to support
      the presence of an autocrine/paracrine mechanism of proliferation control
      involving the PDGF ligand/receptor system in human MFHs.

PMID- 14666647
TI  - Effective chemoradiotherapy without additive toxicity in locoregionally advanced
      head and neck cancer.
AB  - A previous preclinical study revealed that the maximum additive effect between
      chemotherapy (CT) and irradiation (RT) occurred at a low level of CT. Therapy was
      therefore designed with an oral drug daily given in combination with RT in order
      to determine the efficacy and toxicity. Locoregionally advanced head and neck
      tumor patients were treated with simultaneous RT and CT. RT was administered 5
      times per week at 2 Gy per fraction to a total dose of 70 Gy. Throughout the
      treatment 30 mg/kg Tegafur was given daily orally. In the period between 2000 and
      2002, 50 patients were enrolled. In 60%, complete remission was attained with an
      overall response rate of 94%. Acute mucositis of grade 2 or 3 was observed in 56%
      (28 patients), while gastrointestinal and hematological toxicity of grade 2 or 3
      occured in 8% (4 patients). Because of side-effects, the duration of treatment
      was at most 2 weeks long. Toxicity was eliminated quickly by careful supportive
      therapy. In conclusion, it is considered that oral low-dose CT in combination
      with RT is an efficient and simple mode of treatment for locally advanced head
      and neck tumor patients with a poor prognosis.

PMID- 14666648
TI  - GSTM1 and GSTT1 polymorphisms, tobacco and risk of lung cancer: a case-control
      study from Galicia, Spain.
AB  - BACKGROUND: Only 15% of heavy smokers go on to develop lung cancer, indicating
      the existence of individual predisposition. PATIENTS AND METHODS: Using a case
      control study, we ascertained whether there were differences between cases and
      controls in the frequency of GSTM1 and GSTT1 gene polymorphisms, and whether
      their effect might be linked to smoking habit. RESULTS: While a risk of lung
      cancer of 1.7 (1.0-3.0) was observed for GSTM1 gene deficiency, there appeared to
      be no such association for absence of the GSTT1 gene. The interaction observed
      with tobacco use indicated an excess risk of 24.5% (IC 95%-59.8-109.0) for the
      GSTM1 gene, with no such interaction in evidence for the GSTT1 gene. The highest
      risk for a combination of the different haplotypes was for subjects with the
      GSTT1 gene present and the GSTM1 gene deleted, with an Odds Ratio of 2.19 (1.18
      4.07). CONCLUSION: The absence of the GSTM1 gene is, while that of the GSTT1 gene
      is seemingly not, implicated in susceptibility to lung cancer.

PMID- 14666649
TI  - First-line intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in
      locally advanced breast cancer.
AB  - BACKGROUND: Approximately 20% of patients with breast cancer present with locally
      advanced disease without distant metastases. This phase II double-center trial
      aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone
      (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy
      (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty
      six patients with locally advanced disease and no prior exposure to
      anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq
      and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1,
      every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian,
      internal mammary and lateral thoracic arteries was obtained in all patients,
      followed by infusion of a blue dye solution into the arteries to determine the
      most appropriate vessel that supplies the tumor area. RESULTS: Objective
      responses, confirmed at least 4 weeks after the first documentation, were
      observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of
      the patients showed complete tumor regression, operative removal or toilet
      mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%.
      A total of 25 mastectomies were carried out for 36 patients. Four patients had
      bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two
      of which presented with complete infiltration of normal breast tissue. The median
      time to progression and median overall survival were 11 and 27 months,
      respectively. The time to local response was 3 weeks and time to mastectomy was 9
      weeks. Transient neurological disorders developed in six patients and skin
      chemical burns with painful inflammatory reactions were encountered in ten
      patients. No systemic toxicity was observed in terms of bone marrow depression
      and hair loss. No cardiotoxicity was observed. In all specimens necrosis was
      reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination
      of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC
      appears to be a safe and well tolerated treatment for locally advanced breast
      cancer without clinical evidence of distant metastases. When combined with
      surgery it offers interesting results in terms of local control and allows a high
      rate of mastectomies in otherwise inoperable cases.

PMID- 14666650
TI  - Diagnostic value of urinary molecular markers in bladder cancer.
AB  - OBJECTIVES: In an attempt to find a more sensitive and specific non-invasive
      diagnostic assay for the detection of bladder cancer cells, the authors assayed
      the exfoliated cells from patient's voided urine and bladder washing fluids for
      the presence of telomerase, an enzyme that maintains a cell's chromosomal length,
      metalloproteinase-9 (MMP-9), which has been associated with tumor cell invasion
      and metastasis. Their results were compared with both voided urine cytology (VUC)
      and bladder wash cytology (BWC) for the detection of bladder cancer cells.
      MATERIALS AND METHODS: The authors used preoperative voided morning urine samples
      from 110 subjects for telomerase, matrix metalloproteinase-9 (MMP-9) and
      cytology. Bladder wash samples were obtained for telomerase and cytology. Of 110
      cases 73 were histologically diagnosed as bladder cancer, whereas the remaining
      16 had benign urological disorders. A group of 21 healthy volunteers were also
      enrolled in this study. Cystoscopy was done for all patients as the reference
      standard for the identification of bladder cancer. Biopsy of any suspicious
      lesion was performed for histopathological examination. RESULTS: Receiver
      operator characteristics (ROC) curves were used to determine the optimal
      threshold values for telomerase activity in urine, bladder wash and MMP-9 [0.05,
      0.088 and 0.51 (ng/ml), respectively]. The levels and the positivity rates of
      telomerase activity and MMP-9 were significantly higher in the malignant group
      compared to either the benign group or normal controls. Bladder cancer patients
      with positive cytology revealed positive telomerase activity in urine, bladder
      wash, and MMP-9 in 92%, 87% and 61%, respectively. Also, these positive rates
      were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%,
      respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall
      sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase
      activity in urine, and in bladder wash, respectively. 66.6% and 80% for MMP-9,
      58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash
      cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher
      than either combined sensitivity of VUC with one of the biomarkers or than that
      of the biomarker alone. CONCLUSION: Urinary telomerase and MMP-9 had superior
      sensitivities over VUC; moreover, combined use of these markers increased the
      sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers
      in bilharzial bladder cancer than non-bilharzial type highlight their clinical
      utility in screening patients with urinary bilharziasis.

PMID- 14666651
TI  - Colorectal cancer screening in asymptomatic adults: the role of FDG PET scan.
AB  - The aim of this study was to evaluate the potential application of 18F
      fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) for colorectal cancer
      screening in asymptomatic individuals. The subjects consisted of 3210 physical
      check-up examinees (1736 men, 1474 women; mean age +/- SD, 53.2 +/- 8 y) with non
      specific medical history. In the control group, 12 patients who had
      gastrointestinal symptoms with biopsy-proved colon carcinoma were recruited.
      Whole-body FDG PET was performed on all patients. Focal hypermetabolic areas with
      an intensity equal to or exceeding the level of FDG uptake in the brain and
      bladder were considered abnormal and interpreted as intraluminal neoplasia. Among
      the 3210 FDG PET examinations, advanced neoplasm was present in 20 examinations,
      including 2 tubular adenomas larger than 1 cm, 12 villous adenomas and 6 cancers.
      Of 6 examinees diagnosed with cancer, one had a Dukes stage A lesion, four had
      Dukes stage B lesion and one had a Dukes stage C lesion. In the control group, of
      12 patients with biopsy-proved carcinoma followed by FDG PET scan, six had a
      Dukes stage B lesion, four had Dukes stage C lesion and two had a Dukes stage D
      lesion. The mean and standard deviation of standard uptake value (SUV) in colonic
      adenoma and carcinoma is 3.56 +/- 0.68 and 5.74 +/- 2.26, respectively. The
      sensitivity of using FDG PET in the detection of primary colorectal cancer is
      high. Primary colorectal cancer can be detected with FDG PET in a resectable
      stage. FDG PET could detect large size (> 0.7 cm) and pre-malignant change of
      colonic adenoma. It is possible to differentiate adenoma from carcinoma of colon
      by an increased rate of glycolysis (SUV) in carcinoma.

PMID- 14666652
TI  - Inhibition of breast cancer cell growth by the Wilms' tumor suppressor WT1 is
      associated with a destabilization of beta-catenin.
AB  - The Wilms' tumor suppressor gene, wt1, encodes a zinc-finger protein, WT1, that
      functions as a potent inhibitor of cell growth. The findings that expression
      levels of WT1 were down-regulated in breast cancer cell lines and in subsets of
      primary breast tumors led us to investigate the possible role of WT1 in
      tumorigenesis of breast cancer. We have established stable cell lines from a
      breast cancer cell line MDA-MB-231 to express exogenous WT1, and investigated the
      ability of WT1 to inhibit the transformed phenotype of MDA-MB-231 cells. We found
      that WT1 suppressed clonal growth of MDA-MB-231 cells in soft-agar and inhibited
      tumor growth of these cells in nude mice. We also found that the steady state
      levels of beta-catenin protein and the transcription activity of beta-catenin/Tcf
      signaling pathway were dramatically decreased in WT1-transfected cells. This
      decrease of beta-catenin was associated with increased levels of beta-catenin
      phosphorylation. Furthermore, the expression levels of GSK-3 beta, the kinase
      that phosphorylates beta-catenin and signals its degradation, were up-regulated
      in WT1-transfected cells. The results suggest that WT1 inhibits the transformed
      phenotype of breast cancer cells and down-regulates the beta-catenin/TCF
      signaling pathway through destabilization of beta-catenin.

PMID- 14666653
TI  - Antitumor activity of herbal supplements in human prostate cancer xenografts
      implanted in immunodeficient mice.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death in
      American men. Therapeutic options for metastatic prostate cancer are limited. The
      use of herbal therapies in the treatment of this malignancy remains
      controversial. MATERIALS AND METHODS: We tested five herbal supplements,
      designated FB, FM, PP, HF and FBL101, which contain different combinations of
      various natural herbs such as licorice, black cohosh, Dong Quai, false unicorn
      and vitex berry root extracts, fennel seed extract, red clover blossoms extract
      as well as genistein and gamma oryzanol, for antitumor activity in severely
      combined immunodeficient mice bearing CWR22R and PC3 prostate cancer xenografts.
      Their mechanisms of action were also explored. RESULTS: FB, FM, PP, HF and FBL101
      inhibited PC3 tumor growth by 53%, 75%, 80%, 81% and 87%, respectively. In CWR22R
      tumors, similar growth suppression was observed with all supplements. Total
      plasma testosterone levels were not significantly altered by the supplements
      relative to the untreated control. PP and FBL101 significantly reduced VEGF
      levels in PC3 and CWR22R tumors, respectively. Intratumoral microvessel density
      was decreased in PC3 tumors treated with all five supplements but only in CWR22R
      tumors treated with HF. CONCLUSION: Our results demonstrated that herbal
      supplements containing the aforementioned extracts inhibit the growth of prostate
      tumor xenografts, possibly in part by antiangiogenic mechanisms. The potential
      use of these herbal supplements as preventive and therapeutic agents in prostate
      cancer warrants further investigation.

PMID- 14666654
TI  - An outline of the hundred-year history of PDT.
AB  - Photosensitizing drugs have been known and applied in medicine for several
      thousand years. However, the scientific basis for such use was vague or non
      existent before about 1900. Photodynamic therapy, PDT, has now become an
      established treatment modality for several medical indications. Notably, in the
      cases of skin actinic keratosis, several forms of cancer and blindness due to age
      related macular degeneration, PDT has been successful. PDT is the combined
      application of a lesion-localizing photosensitizer and light. PDT with porphyrin
      derivatives as photosensitizing drugs was developed from about 1960. The basic,
      underlying mechanisms for tumour localization of photosensitizers and processes
      explaining the effect of PDT on tumours were elucidated from about that time. It
      has become clear that PDT is efficient only in the presence of oxygen, and that
      the oxygen dependency of PDT is similar to that of X-rays. Singlet oxygen, 1O2, a
      short-lived product of the reaction between an excited sensitizer molecule and
      oxygen, plays a key role. In contrast to radiation therapy and chemotherapy, PDT
      has a low mutagenic potential and, except for skin phototoxicity, few adverse
      effects. Approvals for clinical use of PDT now exist in many countries. The
      annual number of scientific articles on PDT, clinical as well as basic, steadily
      increases and new aspects and applications of it continue to be discovered. Many
      of the new investigators are obviously not aware of the early work in the field
      and repeat many of the experiments that had been reported before the Internet and
      modern data bases were established. Therefore, in the present historical review,
      the early work is weighted more heavily than recent work that is more easily
      accessible to the readers.

PMID- 14666655
TI  - RET tyrosine kinase and medullary thyroid cells are unaffected by clinical doses
      of STI571.
AB  - BACKGROUND: Activating mutations in the RET receptor tyrosine kinase are
      responsible for the development of medullary thyroid cancer (MTC) in persons with
      Multiple Endocrine Neoplasia type 2. We hypothesized that STI571 (Gleevec) would
      inhibit RET kinase and be a useful agent in the treatment of MTC. MATERIALS AND
      METHODS: We determined the IC50 of STI571 for RET using an in vitro kinase assay
      and also examined the effects of STI571 on cellular proliferation and viability
      in TT cells, a human MTC cell line. RESULTS: The average in vitro IC50 of STI571
      for RET is 37 microM +/- 4 microM. Additionally, TT cells incubated with 10
      microM STI571 for up to 8 days showed no apparent reduction in cell proliferation
      or viability. Higher concentrations of STI571, from 25 to 100 microM, induced
      necrosis of TT cells. CONCLUSION: The concentrations of STI571 required to
      significantly inhibit RET and to inhibit TT cell proliferation are not clinically
      achievable. We conclude that STI571 is not likely to be an effective treatment
      for MTC.

PMID- 14666656
TI  - Pervilleine F, a new tropane alkaloid aromatic ester that reverses multidrug
      resistance.
AB  - P-glycoprotein (Pgp)-mediated drug efflux can yield a multidrug resistance (MDR)
      phenotype that is associated with poor response to cancer chemotherapy.
      Pervilleine F, a new tropane alkaloid aromatic ester obtained from a chloroform
      extract of the roots of Erythroxylum pervillei as the result of bioactivity
      guided fractionation, was found to restore the vinblastine sensitivity of
      cultured multidrug-resistant KB-V1 cells, with an IC50 value of 0.40 microM.
      Pervilleine F (8 microM) was also able to partially reverse the cross-resistance
      of KB-V1 cells to the clinically used or experimental anticancer agents
      actinomycin D (45.1-fold), baccatin III (> 3.4-fold), daunomycin (> 22.5-fold),
      ellipticine (1.9-fold), mithramycin A (42.5-fold), podophyllotoxin (1.6-fold),
      paclitaxel (32.2-fold) and vincristine (73.6-fold). While pervilleine F alone at
      the concentration of 10 microM had no significant effect on the KB-V1 cell cycle,
      pervilleine F (at concentrations of 0.2, 1, 2, and 8 microM) combined with
      vinblastine (1 microgram/ml) induced dose-dependent G2/M phase arrest, ranging
      from 20.2, 51.0, 63.7, to 79.5%, as an indication of the restoration of
      vinblastine sensitivity. To confirm this activity with an in vivo animal model,
      KB-V1 cells were placed in hollow fibers and implanted into NCr nu/nu mice. Cell
      growth was not significantly inhibited when vinblastine or pervilleine F was
      administered as single agents, but when these two compounds were used in
      combination, inhibition of up to 64.1% was observed. Equimolar doses of verapamil
      were less effective. These data suggest that pervilleine F is an effective
      inhibitor of Pgp and should be further evaluated for clinical utility.

PMID- 14666657
TI  - The hepoxilin analog PBT-3 induces apoptosis in BCR-ABL-positive K562 leukemia
      cells.
AB  - BACKGROUND: Leukemia is a heterogeneous disease characterized by malignant
      proliferation of cells of the hematopoietic system. The use of chemotherapeutic
      agents is still the mainstay of anti-leukemia therapy. Despite this, significant
      morbidity and mortality still occurs. We describe herein novel apoptotic effects
      of PBT-3, one of a family of stable analogs of the Hepoxilins, natural products
      derived from arachidonic acid. MATERIALS AND METHODS: Inhibition of [3H]
      thymidine incorporation, nuclear fragmentation, DNA laddering, FACS analysis as
      well as Annexin V binding were assessed. RESULTS: PBT-3 dose-dependently causes
      apoptosis of the CML cell line, K562, in vitro. PBT-3 acts by increasing
      cytochrome c release into the cytoplasm and by activation of caspase-3
      degradation. The effects of PBT-3 compare favorably with those of STI571
      (Gleevec), while thromboxane agonists and antagonists are without effect.
      CONCLUSION: These results suggest that PBT analogs may provide a new platform for
      the development of apoptotic drugs in leukemia.

PMID- 14666658
TI  - Camptothecin and 9-nitrocamptothecin (9NC) as anti-cancer, anti-HIV and cell
      differentiation agents. Development of resistance, enhancement of 9NC-induced
      activities and combination treatments in cell and animal models.
AB  - The anticancer drug, 9-nitrocamptothecin (9NC), has demonstrated an unprecedented
      activity against human caner cells grown in cultures and as xenografts in nude
      mice. 9NC-induced apoptosis of cancer cells is mediated by the nuclear enzyme,
      topoisomerase I, and executed by pathways that involve cytochrome c release from
      the mitochondrion and/or activation of death receptors depending on the cell
      type. Alternatively, 9NC has exhibited ability to induce differentiation or
      senescence of certain cell types in vitro. In several instances, the 9NC
      activities can be regulated by Bcl-2 family proteins and cell cycle-associated
      proteins, p53, p21 and Cdks. Also, 9NC can inhibit HIV replication in infected T-
      and monocytic cells in vitro. Development of resistance to 9NC, associated with
      mutations in the topoisomerase I gene, can be overcome by regulating specific
      proteins, such as RKIP, other than topoisomerase I. Finally, derivatives (i.e.,
      alkyl esters) of 9NC, liposome-encapsulated 9NC and combined treatment of 9NC
      with ionizing radiation or hyperthermia are other approaches to enhance the
      apoptotic activity of 9NC against human cancer cells.

PMID- 14666659
TI  - Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine
      kinase inhibition.
AB  - From immunohistochemical and ligand-binding studies, it is known that the
      epidermal growth factor receptor (EGFR), a member of the erbB family of
      receptors, is expressed in tissues of epithelial, mesenchymal and neuronal origin
      and plays a major role in normal cellular processes such as proliferation,
      differentiation and development. EGFR is highly expressed in a number of solid
      tumours and its expression correlates with tumour progression, resistance to
      chemotherapy and a poor prognosis; it is consequently an attractive target for
      the rational design of novel anticancer agents. Knowledge of the role of EGFR in
      normal tissues will help the understanding of the adverse events associated with
      such agents. Studies in knockout mice and preclinical toxicology studies have
      shown that the major effects of inhibiting the EGFR are skin and gastrointestinal
      toxicities. Clinical studies with inhibitors of EGFR, such as gefitinib,
      cetuximab and erlotinib, have shown a favourable adverse-event profile, primarily
      consisting of skin and gastrointestinal toxicities, as predicted from the
      mechanism-based effects observed in preclinical studies.

PMID- 14666660
TI  - 2B4(CD244)-mediated activation of NK cells reduces metastases of B16F10 melanoma
      in mice.
AB  - BACKGROUND: Natural killer (NK) cells are a third population of lymphocytes that
      can kill certain tumor cells. This killing is regulated by signals received
      through activating and inhibitory receptors. 2B4 (CD244), a member of the CD2
      subset of Immunoglobulin superfamily, was identified as an activating receptor on
      NK cells. Interaction of 2B4 with its ligand CD48 or anti-2B4 mAb stimulates NK
      cell cytolytic function as well as production of INF-gamma. MATERIALS AND
      METHODS: A murine tumor model was used to study the in vivo role of 2B4. 2B4 and
      CD48 were activated in vivo by injecting anti-2B4 and anti-CD48 monoclonal
      antibodies. RESULTS: Activation of 2B4 or CD48 resulted in a five-fold reduction
      in tumor metastasis. IFN-gamma knockout mice had a two-fold increase in
      metastasis as compared to wild-type after 2B4 activation. CONCLUSION: Activation
      of 2B4 and CD48 reduces metastasis of B16F10 melanoma cells and this anti-tumor
      effect involves both cytolytic function and cytokine production.

PMID- 14666661
TI  - c-IAP1 is overexpressed in HL-60 cells selected for doxorubicin resistance:
      effects on etoposide-induced apoptosis.
AB  - BACKGROUND: We previously demonstrated that KN-62, an inhibitor of calcium
      calmodulin-dependent enzymes, sensitizes human leukemia HL-60 cells resistant to
      topoisomerase II-targeting drugs. The objective of this study was to determine
      pathways of apoptosis downstream of DNA damage induced by KN-62 co-treatment with
      VP-16. MATERIALS AND METHODS: HL-60/Y/DOX0.05 cells were treated with VP-16, KN
      62, or VP-16 + KN-62. Following treatment, cells were assayed for c-IAP1, c-IAP2
      and XIAP protein expression, as well as caspase activation, cytochrome c release
      and PARP cleavage. RESULTS: Baseline c-IAP1 protein levels were 2-fold higher in
      HL60 cells selected for resistance to doxorubicin compared to the parent
      sensitive line. VP-16 and KN-62 co-treatment was associated with caspase
      activation via the mitochondrial pathway and significant reductions (p = 0.002)
      in c-IAP1 protein expression but not with c-IAP2 or XIAP. CONCLUSION: These data
      suggest that KN-62 co-treatment sensitizes doxorubicin-resistant cells to VP-16
      induced apoptosis by enhancing caspase activity and reducing c-IAP1 expression.

PMID- 14666662
TI  - High ceramide content liposomes with in vivo antitumor activity.
AB  - BACKGROUND: The pro-apoptotic activity of ceramide lipids has made this an
      exciting new target for therapeutic manipulation. While approaches using
      exogenous application of short-chain ceramides and modulation of endogenous
      ceramide levels via manipulation of metabolic pathways have been explored,
      controlled delivery of natural ceramide has not been previously reported. In this
      paper we describe the formulation of novel liposomes containing high levels of
      natural ceramide in the lipid bilayer for the purpose of controlled ceramide
      delivery. MATERIALS AND METHODS: Liposomes were characterized by cryo
      transmission electron microscopy, quasi-elastic light scattering and trapped
      volume analysis. Pharmacokinetic analysis was performed following i.v. bolus
      dosing, and antitumor activity was evaluated following i.v. bolus and i.p. dosing
      in the J774 ascites tumor model. RESULTS: Stable ceramide-containing liposomes
      exhibited pharmacokinetic properties suitable for in vivo applications and
      resulted in an increase in lifespan of greater than 20% compared to control
      liposomes following i.v. bolus and i.p. administration. CONCLUSION: This work
      demonstrates proof-of-concept that delivery of exogenous natural ceramide lipid
      has antitumor activity in vivo, and highlights the potential utility of ceramide
      based liposomes as a novel strategy for cancer chemotherapy based on controlled
      ceramide delivery.

PMID- 14666663
TI  - Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: I. In
      vitro studies of adhesion, migration and invasion of MDA-MB 231 human breast
      cancer cells.
AB  - BACKGROUND: The anti-cancer agent inositol hexaphosphate (IP6) is an abundant
      intrinsic component of both plant and mammalian cells. In addition to inducing
      differentiation and inhibiting growth of numerous cancer cell lines in vitro, IP6
      has been demonstrated to prevent and abrogate both primary tumor and metastasis
      in vivo. MATERIALS AND METHODS: Using MDA-MB 231 human breast cancer cells, we
      studied the potential of IP6 to inhibit cell adhesion, migration and invasion,
      the key steps in cancer metastasis, utilizing the extracellular matrix (ECM)
      proteins, a culture wounding assay, modified Boyden chambers, immunocytochemistry
      and zymography. RESULTS: IP6 treatment caused a 65% reduction of cell adhesion to
      fibronection (p = 0.002) and a 37% reduction to collagen (p = 0.005). To
      determine whether a decrease in cell adhesion leads to a decrease in cell
      motility, migration assays were performed; IP6 decreased both the number of
      migrating cells and the distance of cell migration into the denuded area by 72%
      (p < 0.001). Haptotatic cell migration in a modified Boyden chambers was also
      reduced in a dose-dependent manner. While cell migration on fibronectin was
      inhibited by 65% (p < 0.001), migration on collagen and laminin was decreased by
      32% (p < 0.01) and 13% (p < 0.05), respectively. Immunocytochemistry revealed the
      absence of lamellipodia structure in IP6-treated cells as compared to untreated
      cells, corresponding to a diminished ability of cancer cells to form cellular
      network as determined by Matrigel outgrowth assay. Likewise, cell invasion also
      was decreased (by 72% after IP6 treatment, p = 0.001) in a dose-dependent
      fashion. Additionally, IP6 significantly (p = 0.006) inhibited the secretion of
      matrix metalloproteinase (MMP)-9 as assessed by zymography. CONCLUSION: The
      results of this study show that IP6 inhibits the metastasis of human breast
      cancer cells in vitro through effects on cancer cell adhesion, migration and
      invasion.

PMID- 14666664
TI  - Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: II.
      Effects on integrins and focal adhesions.
AB  - BACKGROUND: We have shown that inositol hexaphosphate (IP6), a natural compound
      and a potent anti-cancer agent, inhibited cancer cell adhesion to the
      extracellular matrix (ECM) proteins, thereby leading to inhibition of cell
      migration and invasion. Cell adhesion to ECM is mediated by specific cell surface
      integrins, which transduce intracellular signals through their interaction and
      activation of other proteins that are recruited to the focal adhesion. We
      hypothesize that IP6 decreases cell adhesion by suppressing the integrin
      receptors and their subsequent signaling pathway. MATERIALS AND METHODS: We
      analyzed integrin expressions of the highly invasive estrogen receptor-negative
      human breast cancer MDA-MB 231 cells exposed to IP6 by flow cytometry. The
      expression of focal adhesion proteins was investigated by immunocytochemistry and
      Western blotting. RESULTS: IP6 treatment caused a significant (P < 0.005)
      decrease in the expression of integrin heterodimers alpha 2 beta 1 (collagen
      receptor), alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin
      receptor); flow cytometry showed that it was the alpha 5 subunit that was down
      regulated ( < 0.001). However, the expression of the alpha 2, alpha v, beta 1 and
      beta 3 subunits were not affected by IP6 treatment. When the expression of
      integrins on the cell surface was assessed, there was a dramatic 82% decrease in
      the expression of alpha 5 beta 1 on IP6-treated cells (P < 0.0001), indicating a
      decrease in cell surface expression of the heterodimers. No effect was seen when
      inositol hexasulfate (IS6), an analogue of IP6, was used as a control.
      Immunocytochemistry showed a lack of clustering of paxillin; tyrosine
      phosphorylated proteins in IP6-treated cells were discontinuous and scattered
      around the cell periphery, whereas the patterns were more dense and localized in
      control cells. Consistent with these observations, focal adhesion kinase (FAK)
      autophosphorylation at tyrosine-397 residue was suppressed, albeit modestly, by
      IP6 treatment, suggesting a down-regulation in the integrin-mediated signaling
      pathway. CONCLUSION: The results of this study indicate that IP6-induced
      inhibition of cancer cell adhesion, migration and invasion may be mediated
      through the modulation of integrin dimerization, cell surface expression and
      integrin-associated signaling pathway.

PMID- 14666665
TI  - Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in
      the peritoneal dissemination of gastric cancers.
AB  - Our previous study using cDNA microarray showed that differentially expressed
      genes among gastric cancer cells involved in peritoneal dissemination could be
      positively identified. One of these genes, which is overexpressed, is inositol
      1,4,5-trisphosphate receptor type 3 (IP3R3). IP3R3 is responsible for the
      intracellular Ca2+ release channel and for mobilizing stored Ca2+. Three
      different receptor types have been molecularly cloned and their genes have been
      classified into a family. However, the role of the IP3 signaling pathway in the
      peritoneal dissemination of gastric cancer is still unclear. In the study
      presented here, the IP3R3 is showed to be overexpressed in gastric cancer cell
      lines established from malignant ascites, but weakly expressed in a gastric
      cancer cell line established from primary tumor as well as normal gastric
      epithelial cells. IP3R1 and 2 are only weakly or not expressed in these cells.
      The antagonist of IP3R, 2APB, inhibited cell proliferation and induced apoptosis
      in gastric cancer cells from malignant ascites at concentrations of 100 nM to 100
      microM in a dose-dependent manner. On the other hand, 2APB showed a weak effect
      on other gastric cancer cells established from primary tumors (SNU1), lymph node
      metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and
      myeloid leukemia HL60 cells. This suggests that this inhibitory effect depends on
      the level of IP3R3 expression. As cells which express IP3R3 mRNA (i.e. pancreas
      ascinar cells) are known to have a secretory function in which IP3/Ca2+ signaling
      has been shown to be involved, IP3R3 may be a prerequisite for secretion of an
      enzyme, such as protease, in gastric cancer cells. These results indicate that
      IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and
      that IP3R3 may be a molecular target of the peritoneal dissemination of gastric
      cancer. Its antagonist, 2APB, may thus be useful for the specific treatment of
      peritoneal dissemination of gastric cancer.

PMID- 14666666
TI  - Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag
      A+ strains of Helicobacter pylori.
AB  - BACKGROUND: Ginger root (Zingiber officinale) has been used traditionally for the
      treatment of gastrointestinal ailments such as motion sickness, dyspepsia and
      hyperemesis gravidarum, and is also reported to have chemopreventative activity
      in animal models. The gingerols are a group of structurally related polyphenolic
      compounds isolated from ginger and known to be the active constituents. Since
      Helicobacter pylori (HP) is the primary etiological agent associated with
      dyspepsia, peptic ulcer disease and the development of gastric and colon cancer,
      the anti-HP effects of ginger and its constituents were tested in vitro.
      MATERIALS AND METHODS: A methanol extract of the dried powdered ginger rhizome,
      fractions of the extract and the isolated constituents, 6-,8-,10-gingerol and 6
      shogoal, were tested against 19 strains of HP, including 5 CagA+ strains.
      RESULTS: The methanol extract of ginger rhizome inhibited the growth of all 19
      strains in vitro with a minimum inhibitory concentration range of 6.25-50
      micrograms/ml. One fraction of the crude extract, containing the gingerols, was
      active and inhibited the growth of all HP strains with an MIC range of 0.78 to
      12.5 micrograms/ml and with significant activity against the CagA+ strains.
      CONCLUSION: These data demonstrate that ginger root extracts containing the
      gingerols inhibit the growth of H. pylori CagA+ strains in vitro and this
      activity may contribute to its chemopreventative effects.

PMID- 14666667
TI  - Heat shock protein 70 (HSP70) after laser thermotherapy of an adenocarcinoma
      transplanted into rat liver.
AB  - The heat shock proteins (HSPs) HSP70 and gp96 from necrotic tumour cells are
      considered to function as chaperones in presenting tumour antigens. We therefore
      studied HSP70 and immune cells in a transplantable carcinoma in the liver of rats
      after interstitial laser thermotherapy (ILT). Experiments were performed in
      Wistar FU rats using a dimethyl-hydrazine-induced adenocarcinoma implanted into
      the left lateral lobe of the liver. Rats were randomized to one of the following
      groups: a) ILT of tumour, b) sham ILT, or c) control. ILT was suboptimal and was
      performed at a steady-state temperature of 43 degrees C at the tumour margin for
      30 minutes. Rats were killed 15 minutes, 5 hours, 10 hours, 15 hours or 12 days
      after treatment. Double immunohistochemistry was performed for HSP70 and ED1
      macrophages or CD8 lymphocytes, and ELISA for serum concentrations of HSP70.
      After ILT, there was an increase of HSP70 immunoreactivity in tumours as compared
      to sham ILT. At the same time, tumour cells affected by ILT showed a shift of
      HSP70 from the cytoplasm to the nucleus with a peak at 10 hours. Few CD8-positive
      cells were found. There was an increase of tumour-infiltrating ED1 macrophages
      after ILT as compared to sham ILT at 10-15 hours after treatment. HSP70 was
      present in ED1 macrophages significantly more frequently after ILT than after
      sham ILT, and this was true both for HSP70 localized to the surface and the
      cytoplasm of the macrophage. There was a significant increase in serum HSP70
      during the first 15 hours after ILT. In conclusion, laser thermotherapy resulted
      in increased HSP70 immunoreactivity within tumours and HSP70 shifts from
      cytoplasm to nucleus. Furthermore, it resulted in increased numbers of tumour
      infiltrating macrophages and an increased presence of HSP70 in the membrane and
      cytoplasm of these macrophages.

PMID- 14666668
TI  - Photodynamic therapy for sarcoma pulmonary metastases: a preclinical toxicity
      study.
AB  - BACKGROUND: Intraoperative pleural and interstitial PDT accompanying resection
      may reduce peripheral micrometastatic foci and preclude lobectomy when applied to
      hilar lesions. MATERIALS AND METHODS: Fourteen beagles were used to determine the
      safety and histologic changes resulting from PDT. Photosensitizers HPPH (0.3
      mg/kg) or Photofrin (2.0 mg/kg) were administered i.v. 48 hours prior to
      thoracotomy and light delivery. At thoracotomy interstitial or pleural light was
      given. They underwent necropsy at eight and 30 days. RESULTS: The significant
      toxicitities occurred with pleural PDT using high dose HPPH (15 & 30 J/cm2)
      including pyrexia, elevated WBC and CPK, and respiratory distress. However, using
      single beam pleural surface treatment all light doses for HPPH and Photofrin (5
      40 J/cm2) were tolerated with depths of treatment effect up to 10 mm with HPPH.
      CONCLUSION: Histologic and clinical changes associated with interstitial and
      pleural PDT were acceptable after dosimetry was adjusted. PDT holds promise as an
      adjuvant treatment for sarcoma pulmonary metastases.

PMID- 14666669
TI  - Effect of antioxidants, oxidants, metals and saliva on cytotoxicity induction by
      sodium fluoride.
AB  - We have recently found that millimolar concentrations of sodium fluoride (NaF)
      induced apoptotic cell death, characterized by caspase activation and DNA
      fragmentation, in tumor cell lines. This finding paved the way to investigating
      the interaction between NaF and the oral environment. As an initial step, we
      investigated redox compounds, metals and saliva, which may modify the cytotoxic
      activity of NaF against a human oral squamous cell carcinoma cell line (HSC-2).
      The minimum exposure time to NaF required for cytotoxicity induction was 8 hours.
      Noncytotoxic concentrations of antioxidants (sodium ascorbate, gallic acid,
      epigallocatechin gallate, chlorogenic acid, curcumin, superoxide dismutase,
      catalase), oxidants (hydrogen peroxide, sodium hypochlorite), metals (CuCl,
      CuCl2, FeCl2, FeCl3, CoCl2) or saliva neither protected against, nor enhanced the
      cytotoxic activity of NaF. Cytotoxic concentrations of these compounds produced
      somewhat additive, but not synergistic, effects on the cytotoxicity of NaF. ESR
      analysis demonstrated that NaF did not apparently change the radical intensity of
      sodium ascorbate and gallic acid, measured under alkaline conditions. During the
      cell death induction in human promyelocytic leukemia HL-60 cells by NaF, the
      consumption of glucose rapidly declined, followed by a decline in the consumption
      of major amino acids. The present study suggests that the cytotoxic activity of
      NaF is not regulated by the redox mechanism, but rather linked to the rapid
      decline in glucose consumption at early stage.

PMID- 14666670
TI  - Effect of S. cerevisiae APN1 protein on mammalian DNA base excision repair.
AB  - Mammalian cells transfected with the S. cerevisiae APN1 protein acquire
      resistance to oxidizing agents, the damage of which is mainly repaired via DNA
      base excision repair (BER). We have recently hypothesized that this effect might
      be linked to the possible capacity of APN1 to accelerate mammalian BER by its 3'
      diesterase activity. We have investigated here the effect of pure APN1 protein on
      BER performed by mouse embryonic fibroblast extracts. No significant acceleration
      was observed in the repair of either a single AP site cleaved by the bifunctional
      glycosylase NTH of E. coli or the repair of a single 8-oxoguanine, initiated by
      the bifunctional glycosylase OGG1. Similarly, no significant effect was observed
      on the repair of a single U (initiated by the monofunctional glycosylase U DNA
      glycosylase) or the repair of a single natural abasic site. The inability of APN1
      to increase the efficiency of BER initiated by bifunctional glycosylases
      indicates that removal of 3' blocking fragments is not the rate-limiting step of
      this repair pathway.

PMID- 14666671
TI  - Constitutive expression of Rb associated protein 46 (RbAp46) reverts transformed
      phenotypes of breast cancer cells.
AB  - The retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) is a subunit of
      chromatin modifying and remodeling complexes. Previously, we found that RbAp46
      functions as a potent growth inhibitor. It is also a downstream effector of the
      Wilms' tumor suppressor, WT1. The findings that expression levels of WT1 were
      down-regulated in breast cancer cell lines and in subsets of primary breast
      tumors led us to investigate the possible role of RbAp46 in breast cancer
      tumorigenesis. Here, we found that RbAp46 expression levels were decreased in
      five established breast cancer cell lines compared to a normal mammary gland
      epithelial cell line. To investigate the effect of constitutive expression of
      RbAp46 on the transformed phenotypes of breast cancer cells, we established
      stable cell lines that constitutively express exogenous RbAp46 using three breast
      cancer cell lines, MCF-7, MDA-MB-231 and MDA-MB-436. We have found that RbAp46
      expression suppressed colony formation of these breast cancer cells in soft-agar,
      and inhibited tumor formation of these cells in nude mice. Our data demonstrated
      that constitutive RbAp46 expression suppresses the transformed phenotypes of
      breast cancer cells, and suggested that dysregulation of RbAp46 expression may
      contribute to breast cancer tumorigenesis.

PMID- 14666672
TI  - Augmented gene expression of quinone reductase by 6-(methylsulfinyl)hexyl
      isothiocyanate through avoiding its cytotoxicity.
AB  - We examined both the induction of quinone reductase (QR) by 6
      (methylsulfinyl)hexyl isothiocyanate and its cytotoxicity in Hepa1c1c7 cells, and
      compared the sensitivity of these two responses to NAC. QR activity was increased
      by 6-(methylsulfinyl)hexyl isothiocyanate in a dose-dependent manner. At 80
      microM, the compound was significantly toxic to cells, but the resulting QR
      inhibition was dose-dependently overcome by NAC. Augmentation of QR activity by 6
      (methylsulfinyl)hexyl isothiocyanate seemed to be due to augmented expression of
      QR mRNA, which was significantly increased by the compound. Inhibition of QR gene
      expression was seen at 80 microM and could be overcome by NAC. Optimal induction
      of QR gene expression by the compound (at 40 microM) was slightly but
      significantly inhibited by 10 mM NAC but not by 1 mM. The present study suggests
      that induction of Phase 2 detoxification enzymes by isothiocyanate compounds may
      be further enhanced by suppression of their inherent cytotoxic activity.

PMID- 14666673
TI  - Nuclear localization of beta-catenin is correlated with the expression of cyclin
      D1 in endometrial carcinomas.
AB  - BACKGROUND: beta-catenin has recently been reported to act as a cell growth
      promoter through cyclin D1 transcription. However, the correlation between beta
      catenin and cyclin D1 expressions is not fully understood in endometrial tissues.
      MATERIALS AND METHODS: Immunohistochemical expression of beta-catenin was
      examined in normal endometria (32 cases) and endometrial carcinomas (82 cases),
      and its expression was compared with that of cyclins (D1, E, A, B1). RESULTS:
      Sporadic nuclear staining of beta-catenin and cyclins was observed from
      proliferative phase of early secretory phase endometria, however, spacial
      correlations between beta-catenin and cyclins were not evident. In endometrial
      carcinomas, positivity for nuclear beta-catenin and cyclins increased compared to
      the normal endometria. Topologically, the cyclin D1-positive cells were
      frequently found in nuclear beta-catenin-positive cells. In addition, Spearman's
      rank correlation analysis revealed that the nuclear expression of beta-catenin
      correlated positively with that of cyclin D1 (p < 0.0001). CONCLUSION: The beta
      catenin-cyclin D1 pathway might be involved in the growth of endometrial
      carcinomas.

PMID- 14666674
TI  - Intracerebral C6 glioma model in female hairless rats: assessment by using MRI
      and follow-up of irradiation.
AB  - An experimental intracerebral C6 glioma model in immunosuppressed female hairless
      rats has been developed. The rate of tumor uptake was evaluated by magnetic
      resonance imaging (MRI), using specific sequences without gadolinium enhancement.
      Twenty-four hours before intracerebral transplantation, a control cranial MRI was
      carried out and rats underwent a total body irradiation (TBI). MRI was repeated
      seven days after transplantation in order to monitor tumor uptake. Then, twelve
      days after transplantation, tumors were treated with two different protocols of
      radiotherapy: 3 Gy during 5 days or 0.7 Gy three times a day during 5 days (ultra
      fractionation). A third MRI was performed 21 days after intracerebral
      transplantation. Eventually, all the rats were sacrificed and histological
      analysis of the tumors was performed. Our results show that TBI efficiently
      increases the rate of tumor uptake. Thereafter, tumor formation and growth as
      well as the efficiency of a therapy (radiotherapy in our case) can be monitored
      with MRI (without gadolinium enhancement). Treatment of C6 glioma tumors with
      ultrafractionation was a marked improvement compared to a more traditional
      radiotherapy treatment. We developed a model that is useful for the study of new
      glioma treatment. We also obtained promising preliminary results when using ultra
      fractionation radiotherapy.

PMID- 14666675
TI  - A new orthotopic model of human breast cancer in immunocompetent rats.
AB  - BACKGROUND: Breast cancer is the first cause of mortality by cancer in women in
      North America and Western Europe. For non-estrogen-dependent tumors as well as
      for metastatic cancers, current therapies are of limited efficacy. Several animal
      models have been described but they are imperfect as they are poorly
      representative of what occurs in real tumors. To overcome some of these
      limitations, we describe a new orthotopic model of estrogen-independent breast
      cancer in immunocompetent rats treated with cyclosporin A (CysA). MATERIALS AND
      METHODS: Injection of cell suspensions of human breast MDA-MB-231 cancer cells
      into the mammary fat pad or subcutaneous grafts of solid tumor sections were
      performed on Sprague Dawley rats receiving intraperitoneally 35 mg/kg of CysA.
      Tumor growth was measured and monitored by scintigraphy using 18FDG and 99mTc
      MIBI. RESULTS: In both models, tumors grew well but growth rates were different.
      Cell suspension injections gave rise to tumors with a higher growth rate and the
      tumors obtained infiltrated the mammary and giving results closer to human
      pathology. CONCLUSION: This animal model with injected cells may provide a new
      adequate tool for studying breast cancer and developing new therapy strategy.

PMID- 14666676
TI  - Placental growth factor gene expression in human prostate cancer and benign
      prostate hyperplasia.
AB  - BACKGROUND: Angiogenesis plays a crucial role in normal development and
      carcinogenesis of prostate glands. Placental growth factor (PlGF) belongs to the
      same family as the vascular endothelial growth factor. The presence of PlGF in
      human prostate has not been studied. In the current study, we investigated the
      gene expression profiles of PlGF in human prostate. MATERIALS AND METHODS: Gene
      expression of PlGF-1 and PlGF-2 was assessed by RT-PCR and direct sequencing.
      Gene expression levels were quantified by real-time PCR, and we compared the
      transcript levels among benign prostate hyperplasia (BPH), prostate caner (CAP)
      and CAP after androgen deprivation therapy (CAP-Tx). RESULTS: Human prostate
      cancer cells, LNCaP, PC-3 and DU-145, expressed both PlGF-1 and -2 mRNAs. Human
      prostate tissues, BPH, CAP and CAP-Tx, also expressed both types of PlGF mRNA.
      BPH and CAP-Tx expressed similar levels of PlGF, however, CAP expressed
      significantly lower levels of PlGF than BPH or CAP-Tx (p < 0.01). CONCLUSION:
      PlGF mRNA was expressed in human prostate. Significantly lower levels of PlGF in
      CAP in comparison with those in BPH or CAP-Tx suggested that PlGF might have
      effects on vasculogenesis and angiogenesis in prostate disease.

PMID- 14666677
TI  - A role for the pituitary tumor-transforming gene in the genesis and progression
      of non-small cell lung carcinomas.
AB  - BACKGROUND: The product of the pituitary tumor-transforming gene (PTTG) inhibits
      chromatid separation, which is considered to promote chromosome instability,
      especially in the absence of the p53 gene product, and also induces basic
      fibroblast growth factor (bFGF) production. Its expression and these variables in
      primary non-small cell carcinomas (NSCLCs) of known p53 status were examined.
      MATERIALS AND METHODS: Comparative genomic hybridization analysis of 78 lesions
      revealed a wide range of total (gain + loss) chromosomal imbalance numbers
      (tCINs). Seven each with the highest and lowest tCINs were examined for PTTG mRNA
      by semi-quantitative RT-PCR and bFGF production immunohistochemically. RESULTS:
      Mean relative values for PTTG mRNA for the tumors and corresponding normal lung
      tissues were 1.46 and 0.88, respectively, the difference being statistically
      significant. Overexpression of bFGF was observed in 12 out of 14 with intense
      immunostaining of carcinoma cells, in contrast to the weak or lack of staining in
      normal lung tissues. However, relative PTTG values did not correlate with tCINs
      or immunoreactivity for bFGF among the tumors regardless of the p53 status.
      CONCLUSION: The results indicate that overexpression of PTTG plays a role in the
      genesis and progression of NSCLCs, although its effects on CINs and bFGF
      production may be obscured by other complicating factors.

PMID- 14666678
TI  - Stem cell recruitment and liver de-differentiation in MMTV-neu (ErbB-2)
      transgenic mice.
AB  - The liver of tumor-bearing hosts manifests fetal phenotypes. We investigated the
      expression of differentiation markers on the liver in MMTV-neu (ErbB-2)
      transgenic mice, in the period from incipient neoangiogenesis to lung
      metastatization. We report AFP expression by hepatocytes in all lobular zones,
      CD34 cell arrest and subsequent hemopoiesis in periportal and mid-zone areas,
      oval-like cells (CD34+, CK19+, AFP+) and ductular reaction in portal tracts,
      portal CK19+ and GGT+ hepatoblast-like cells, and midzonal large dysplastic
      hepatocytes. We hypothesize that CD34 cells are recruited by the tumor from the
      marrow for angiogenic purposes and that their differentiation in the liver is
      influenced by altered liver microenvironment(s). AFP may act as a growth factor
      and biological response modifier for these cells and for the tumor. Dysplasia
      might be enhanced by metabolic stress. We conclude that the liver differentiation
      potential is lobular-zone-dependent and that the risk for eventually developing a
      pre-malignant lesion is not negligible.

PMID- 14666679
TI  - In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric
      cancer.
AB  - BACKGROUND: Gastric adenocarcinoma producing alpha-fetoprotein (AFP) has a very
      poor prognosis. In search of new therapeutic strategies against AFP-producing
      gastric cancer, we examined the efficacy of suicide gene therapy, which has been
      effective on AFP-producing hepatoma. MATERIALS AND METHODS: The herpes simplex
      virus thymidine kinase (HSVtk) gene was transduced into an AFP-producing gastric
      adenocarcinoma cell line, FU97, using adenovirus vectors carrying the constructed
      AFP enhancer/promoter element, followed by ganciclovir (GCV) administration.
      RESULTS: Expression of the transgene was evident in FU97 but not in an AFP
      nonproducing gastric adenocarcinoma cell line, MKN28, which meant that AFP
      enhancer/promoter-specific transcriptional targeting was achieved by the vectors.
      The viability of FU97 but not of MKN28 significantly decreased after the suicide
      gene therapy in vitro. CONCLUSION: Therapeutic application of the AFP
      enhancer/promoter-specific transfer of the HSVtk gene followed by GCV
      administration against AFP-producing gastric cancer deserves attention and
      further research.

PMID- 14666680
TI  - No evidence of stimulation of human tumor cell proliferation by a standardized
      aqueous mistletoe extract in vitro.
AB  - The in vitro antiproliferative or stimulatory activity of an aqueous mistletoe
      extract (AME) with a defined content of bioactive mistletoe lectin (ML) was
      investigated in 6 human tumor cell lines, including two melanomas and
      leiomyosarcomas, each of which had previously been reported to show evidence of
      growth stimulation if treated with low concentrations of isolated ML. The effects
      of AME were compared to that of the standard cytotoxic agent adriamycin (ADR)
      using the well established propidium iodide and sulforhodamin B proliferation
      assays. The AME concentrations used ranged from 0.5 pg to 5 ng (0.82 fMol-85 pM)
      bioactive ML/ml in melanoma (HT-144, SK-MEL-28) and leiomyosarcoma (SK-MLS-1, S
      UT-1B) cell lines and from 0.1-100 ng ML/ml (1.7 pM-1.7 nM) in MCF-7 breast
      cancer and SW620 colon carcinoma cell lines, respectively. The influence of AME
      on cell growth was determined at various time-points from 24 hours to 6 days of
      exposure. We found a time- and cell line-dependent inhibition of tumor cell
      growth, but no reproducible stimulation of tumor cell proliferation. Inhibitory
      concentrations 50% (IC50) for e.g. the SK-MEL-28 melanoma cell line, decreased
      from 4.1 ng ML/ml at 24 hours to 0.16 ng ML/ml at 72 hours and 0.18 ng ML/ml at 5
      days. Our data clearly demonstrate that, by applying scientifically valid methods
      and procedures, the standardized AME did not stimulate tumor cell proliferation
      but showed time- and concentration-dependent antiproliferative effects.

PMID- 14666681
TI  - Expression of osteocalcin in prostate cancer before and after hormonal therapy.
AB  - BACKGROUND: Osteocalcin (OC), a noncollagenous bone matrix protein, is
      specifically produced by osteoblasts. Previously, we demonstrated that OC
      immunohistochemical staining was found in primary prostate cancer (PC) and PC
      metastasis to lymph node and bone. Advanced and metastatic PC is commonly treated
      by hormonal therapy (H/T). Inevitably, these patients will relapse and develop
      hormone-refractory (HR) PC. The aim of this study was to realize the OC
      expression in PC before H/T and after H/T when HRPC developed. MATERIALS AND
      METHODS: Twenty patients with PC received H/T and later developed HRPC. The
      interval of androgen-response was classified by good response (Group A, > or = 30
      months) and poor response (Group B, < 30 months). The mean interval of androgen
      response was 48.8 months in Group A (10 patients) and 17.5 months in Group B (10
      patients). Formalin-fixed paraffin-embedded PC before H/T and HRPC for each
      patient were stained for osteocalcin. RESULTS: Osteocalcin immunohistochemical
      stain was detected in 18 of 20 PC before H/T and 19 of 20 of HRPC. Compared to PC
      before H/T, the expression of OC in HRPC increased in 5 cases (4 of Group A, 1 of
      Group B), did not change in 3 (2 of Group A, 1 of Group B) and decreased in 12 (4
      of Group A, 8 of Group B). CONCLUSION: Our data suggest the expression of OC in
      PC is not correlated to the response of H/T. OC expression was still noted in 95%
      of HRPC. OC may be a target for treatment of HRPC.

PMID- 14666682
TI  - Selectivity of action of glycyrrhizin derivatives on the growth of MCF-7 and HEP
      2 cells.
AB  - Since 1986, there have been reports in the literature that glycyrrhizin (GL), 18
      alpha-glycyrrhetinic acid (18 alpha-GA) and 18 beta-glycyrrhetinic acid (18 beta
      GA) can inhibit the growth of some murine tumours. Recently, testing the activity
      of GL and 18 alpha-GA on human tumour cells, we observed that both substances are
      good anti-proliferative agents, especially on those cells whose replication rate
      is slow. In the present study, the MTT test was performed on MCF-7, Hep-2 and
      VERO cells treated with increasing concentrations of GL and of its derivatives.
      Results showed that the substances do not have a toxic effect on VERO cells and
      that their anti-proliferative effect is evident only on the cell line (MCF-7)
      that evolves slowly. Finally, the TUNEL test revealed the presence of apoptosis
      in MCF-7 cells treated with dosages of GL and 18 alpha-GA, thereby confirming
      that these natural phytoestrogens could be considered as interesting new agents
      for cancer therapy.

PMID- 14666683
TI  - Decreased expression of p107 is correlated with anaplastic transformation in
      papillary carcinoma of the thyroid.
AB  - BACKGROUND: Previous studies have demonstrated that two members of the Rb family,
      pRb and p130, are expressed in thyroid neoplasms. However, our knowledge about
      the expression and physiological role of the third member of this family, p107,
      remains poor. We therefore investigated p107 expression in various thyroid
      neoplasms. MATERIALS AND METHODS: We immunohistochemically investigated p107
      expression in 16 anaplastic carcinomas, 50 papillary carcinomas, 15 follicular
      carcinomas and 17 follicular adenomas using a rabbit polyclonal antibody against
      p107. RESULTS: Normal follicular cells only occasionally expressed p107. In
      papillary carcinoma, p107 was positive in 84.0% of the cases, regardless of
      various biological characteristics. Follicular carcinoma less frequently
      expressed p107 than follicular adenoma (p = 0.0278). Furthermore, only 12.5% of
      anaplastic carcinomas were p107-positive and the incidence was significantly less
      than that in papillary carcinoma (p < 0.0001). CONCLUSION: Our findings suggest
      that p107 plays a constitutive role in the progression of papillary carcinoma and
      that decreased p107 expression may contribute to the transformation from
      follicular adenoma to follicular carcinoma and anaplastic transformation.

PMID- 14666684
TI  - Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I)
      expression in prostatic cancer.
AB  - Despite evidence implicating the insulin-like growth factor (IGF) system in the
      pathogenesis of prostate cancer, its precise role remains unclear. In this study
      we investigated the differential expression of IGF-I, IGF-II and their type I
      receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues.
      Using immunohistochemistry and in situ hybridization techniques, we analyzed 43
      paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with
      prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP)
      counterpart. We then determined a possible correlation of the immunohistochemical
      and in situ findings with two known prognostic clinical-pathological indices:
      Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43
      frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were
      also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues
      examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and
      IGFR-I protein and mRNA; all levels increased significantly from normal tissue to
      PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher
      in epithelium than in stroma, whereas expression of IGF ligands differed. In
      normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in
      epithelium. Conversely, in Pca tissue, both factors were more strongly expressed
      in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR
      I levels highest in the epithelium. IGF-II protein and mRNA reached their highest
      levels in prostate tumors with high Gleason scores. These findings indicate that
      the IGF system changes as prostate tissue progresses from a normal to a malignant
      state. Differential expression of certain IGF system components in Pca may be
      associated with the malignant phenotype and more aggressive tumor behavior. Hence
      IGFs could serve to predict the outcome of prostatic cancer.

PMID- 14666685
TI  - Alpha-fetoprotein-producing esophageal carcinoma: a case report.
AB  - We report herein a rare case of esophageal carcinoma producing alpha-fetoprotein
      (AFP). A 69-year-old man presenting elevated AFP was admitted in order to
      investigate its origin, which several liver examinations done before admission
      had not revealed. At admission, his serum AFP was 76.9 ng/ml whereas other tumor
      markers were within normal range. As the patient complained of mild swallowing
      disturbance, gastrointestinal examinations were performed, and an esophageal
      carcinoma was found at the esophagogastric junction. The patient underwent
      subtotal esophagectomy and the esophagus was reconstructed by gastric tube. The
      postoperative course was uneventful and the serum AFP level normalized
      immediately after the operation. Histopathological examination demonstrated the
      tumor to be poorly-differentiated adenosquamous carcinoma, which contained
      scattered adenocarcinoma composed of clear cells positive to AFP by an
      immunohistochemical stain. The patient has been well for six months after the
      surgery without any sign of recurrence.

PMID- 14666686
TI  - Combination effects of Ara-C and 5-fluorodeoxyuridine against leukemia cells in
      vitro and in mice.
AB  - BACKGROUND: Ara-C (1-beta-D-arabinofuranosylcytosine) is widely used for
      treatment of human leukemia. However, due to emergence of resistance, new drug
      combinations need to be developed. MATERIALS AND METHODS: We tested the
      combination of Ara-C with 5-FdUrd (5-fluorodeoxyuridine) in L1210 and P388D1
      mouse leukemia cells in vitro and in vivo by growth inhibition and recovery assay
      in leukemia-bearing mice. RESULTS: Simultaneous incubation of cells with Ara-C
      and 5-FdUrd yielded more than additive effects for most combinations in both cell
      lines; synergy was seen in P388D1 cells. P388D1 cells showed delayed growth after
      treatment with Ara-C or 5-FdUrd in a growth recovery assay. In animal studies,
      simultaneous subcutaneous administration of the compounds did not show any
      significant beneficial effects as compared with monotherapy. Intraperitoneal
      administration of both compounds, however, significantly prolonged the survival
      of P388D1 animals. CONCLUSION: Depending on cell type and route of drug
      administration, the combination of Ara-C and 5-FdUrd might offer a promising
      additional treatment option for leukemia.

PMID- 14666687
TI  - Prediction of radiosensitivity by measurement of X-ray induced apoptosis in human
      blood using the comet assay.
AB  - BACKGROUND: The aim of this work was to determine whether levels of radiation
      induced apoptosis in human peripheral leukocytes could be used as a predictor of
      radiosensitivity. MATERIALS AND METHODS: Peripheral blood was obtained from
      venous blood and exposed to 0-3 Gy of X-rays. Apoptosis levels were measured at
      4, 24, 48 and 72 hours after exposure using the neutral comet assay. Intra
      individual apoptotic response was measured using repeated blood samples from four
      healthy individuals. Inter-individual variation was investigated in whole blood,
      granulocytes and mononuclear cells from 8 radiotherapy patients (4 demonstrating
      a radiosensitive response and 4 demonstrating a normal response to radiation
      exposures). RESULTS: Amongst the four healthy individuals there was both inter-
      and intra-individual variation of about the same magnitude. However, when
      comparing the apoptotic response of the radiosensitive and normal patients,
      consistent trends were observed at all X-ray doses for all of the patients.
      CONCLUSION: This indicates that apoptosis has some potential as a predictive
      assay, however, large intra-individual variation exists. More studies are
      required to investigate the causes of intra-individual variation and how it might
      be minimized.

PMID- 14666688
TI  - Inositol hexaphosphate inhibits constitutive activation of NF- kappa B in
      androgen-independent human prostate carcinoma DU145 cells.
AB  - BACKGROUND: One practical and translational approach to control prostate cancer
      (PCA) and associated death could be its preventive intervention by dietary
      agents. Several studies in recent years have shown both preventive and
      interventive efficacy of inositol hexaphosphate (IP6) in different animal tumor
      models, however, its effects in PCA and associated mechanisms have not been
      assessed in detail. Since transcription factor NF-kappa B is constitutively
      active in advanced and androgen-independent human PCA DU145 cells, here we
      assessed whether IP6 inhibits this constitutively active NF-kappa B and
      associated upstream effectors and whether such an affect of IP6 has biological
      relevance in causing inhibition of proliferation and induction of apoptosis in
      DU145 cells. MATERIALS AND METHODS: We used DU145 cells and assessed NF-kappa B
      activation by gel shift assay. Western immunoblot and in-beads kinase assay were
      used for protein levels and enzyme activity. Proliferation was measured by BrdU
      labeling and apoptosis by annexin V/PI staining followed by FACS analysis.
      RESULTS: Treatment of cells with 1 and 2 mM doses of IP6 resulted in a strong
      inhibition of NF-kappa B activation, which was consistent with a decrease in
      nuclear levels of NF-kappa B sub-unit proteins p65 and p50. IP6-treated cells
      also showed a strong inhibition in phospho-I kappa B alpha protein levels
      concomitant with a significant increase in total I kappa B alpha levels. This
      effect of IP6 also corroborated with a significant inhibition in IKK alpha kinase
      activity. In other studies, IP6-treated cells showed strong inhibition in cell
      proliferation and induction of apoptosis. CONCLUSION: Our results suggest that
      IP6 could be a potent dietary agent in controlling the growth of advanced PCA
      cells and inducing their apoptotic death, in part, by its inhibitory effect on
      constitutively active NF-kappa B signaling pathway.

PMID- 14666689
TI  - Influence of milk on the antimutagenic potential of green and black teas.
AB  - BACKGROUND: The objective of this study was to evaluate whether addition of milk
      to green, black and decaffeinated black teas alters their antimutagenic activity.
      MATERIALS AND METHODS: Two model mutagens were used, the direct-acting N'-methyl
      N'-nitro-nitrosoguanidine (MNNG) and the indirect-acting 2-amino-3-methylimidazo
      [4,5-flquinoline (IQ), and their mutagenic activity was determined in the Ames
      test, in the presence of tea and milk/tea mixtures. Solids from the milk/tea
      mixtures were removed by centrifugation and the supernatant analysed by HPLC for
      individual catechins and gallic acid in green tea, and thearubigins, theaflavins
      and flavonol glycosides in black teas. RESULTS: Addition of skimmed milk to all
      the teas failed to influence their antimutagenic activity towards the two
      mutagens. Addition of milk to green tea resulted primarily in loss of (-)
      epigallocatechin gallate whereas in the black teas it primarily reduced
      theaflavins levels. CONCLUSION: The antimutagenic activity of green and black
      teas is not modulated by the presence of skimmed milk, even at high
      concentrations.

PMID- 14666690
TI  - Experimental study on different combination schedules of VEGF-receptor inhibitor
      PTK787/ZK222584 and fractionated irradiation.
AB  - BACKGROUND: Inhibition of the vascular endothelial growth factor receptor (VEGFR)
      has been shown to improve the radiation response of several experimental tumors.
      The present experimental study compares the effect of neoadjuvant, concomitant
      and adjuvant treatment with PTK787/ZK222584, a specific inhibitor of the VEGFR,
      in combination with fractionated irradiation. MATERIALS AND METHODS: Growth delay
      after daily oral application of 50 mg per kg bodyweight PTK787/ZK222584 or
      carrier was tested in five different human squamous cell carcinoma growing in
      nude mice. Two of these tumor models, a responder (UT-SCC-14) and a non-responder
      (FaDu), were selected for the irradiation experiments (15 fractions of 2 Gy
      within 15 days). PTK787/ZK222584 was applied daily for 4-18 days and stopped
      before start of irradiation (neoadjuvant), for 15 days during fractionated
      irradiation (concomitant) or for 45 days after the course of irradiation
      (adjuvant). RESULTS: Adjuvant application of PTK787/ZK222584 after fractionated
      irradiation retarded regrowth of UT-SCC-14 tumors and, surprisingly, also of FaDu
      tumors which did not respond to the agent when given alone. No effects on
      radiation response were observed after short-term neoadjuvant or concomitant
      PTK787/ZK222584 application. CONCLUSION: Combined with fractionated irradiation,
      only adjuvant application of PTK787/ZK222584 retarded regrowth of UT-SCC-14 and
      FaDu tumors. The data suggest that preirradiated vasculature might be more
      sensitive to VEGFR inhibition compared to unirradiated vasculature. Whether the
      effect of adjuvant VEGFR inhibition on growth delay translates into improved
      local tumor control after irradiation needs further investigation.

PMID- 14666691
TI  - Sequential increases in 4F2hc expression during DMBA-induced hamster buccal pouch
      carcinogenesis.
AB  - BACKGROUND: Although it is known that amino acid transporters are up-regulated
      for continuous growth in transformed cells, alterations in the 4F2hc expression
      levels between normal and cancer cells are unclear. The purpose of this study,
      therefore, was to examine the alteration of the inducible 4F2hc expression level
      in hamster buccal cancers. MATERIALS AND METHODS: The expression profile of 4F2hc
      on normal buccal mucosa and squamous cell carcinoma (SCC) from different
      differentiation stages in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster
      buccal carcinogenesis was examined using immunohistochemical analysis. RESULTS:
      Immunoreactivity for 4F2hc was detected in almost all the layers of the normal
      mucosa as well as in the tumor cells and keratin layer of SCC. In particular, the
      4F2hc expression level increased progressively via hamster buccal pouch malignant
      progression. CONCLUSION: The results suggest that 4F2hc expression is associated
      with the development of DMBA-induced oral carcinomas. In addition, 4F2hc
      overexpression in SCC indicates that 4F2hc may play an important role in the
      development and progression of oral SCC.

PMID- 14666692
TI  - Quantification of the DHFR gene in blast cells of leukaemia patients by
      fluorescence in situ hybridisation.
AB  - The fluorescence signal intensity of the DHFR gene was analysed in lymphocytes
      from 15 normal donors, in MTX-resistant HeLa cells (carrying DHFR gene
      amplification) and in bone marrow blasts from 16 patients with acute leukaemia
      (AL) by in situ hybridisation. Our aim was to verify if DHFR gene amplification
      may be responsible for increased enzyme activity in leukemic cells. The results
      obtained with a fluorescence in situ hybridisation method were quantified using
      the Scion image software program and compared with cytochemical and
      cytophotometric data relating to DHFR activity. In AL a heterogeneous
      hybridisation pattern was generally observed at the single cell level. However,
      leukemic lymphoblasts showed higher fluorescence signal intensity of the DHFR
      gene as compared with normal lymphocytes, and leukemic myeloblasts a much higher
      signal than lymphoblasts. HeLa cells showed the highest fluorescence signal
      intensity. In all samples enzyme activity behaved in parallel. These results
      indicate that the increased expression of DHFR in leukemic blasts is due to a
      gene amplification. The high levels in AML can explain the MTX natural
      resistance.

PMID- 14666693
TI  - Sex steroid metabolism in human gastric mucosa: 17 beta-hydroxysteroid
      dehydrogenase type 2 in normal, inflamed and neoplastic gastric tissues.
AB  - The 17 beta-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the
      regulation of the biological activity of sex steroids. We analyzed the expression
      of 17HSD type 1 and 2 enzymes which catalyze opposite reactions of estrogen
      metabolism, in normal gastric mucosa and various gastric diseases of 81 tissue
      specimens. No expression of 17HSD type 1 mRNA was observed in any of the
      specimens. 17HSD type 2 mRNA expression was observed in the surface and foveolar
      epithelium of normal gastric mucosa and in the duodenum, while expression was
      weak or absent in glandular epithelium. Gender did not have an effect on
      epithelial expression, but 17HSD type 2 mRNA expression decreased with increasing
      age in both normal and inflamed gastric mucosa (c = 0.6; p = 0.02, Spearman rank
      correlation). In children, the expression in glandular epithelium was
      significantly higher than in adults (p = 0.03). Chronic gastritis was associated
      with decreased expression in surface epithelium (p = 0.023). Regenerating
      epithelium close to ulcers and active gastritis showed up-regulation (p < 0.03).
      Type I intestinal metaplasia showed an up-regulation (p = 0.005) comparable to
      that seen in the duodenum, while type III metaplasia showed decreased expression
      in comparison with type I metaplasia (p = 0.003). Expression was further down
      regulated in cancer (p < 0.003). 17HSD type 2 mRNA expression in gastric and
      duodenal epithelium suggests that estrogen and androgen inactivation and active
      progesterone production are physiological features of gastroduodenal mucosa. The
      higher 17HSD type 2 mRNA expression in normal gastric mucosa of children compared
      to adults may be associated with increased need for protection against the
      mucosal load of foreign substances. The down-regulation associated with aging may
      have relevance in the pathogenesis of gastric cancer.

PMID- 14666694
TI  - Tranilast (N-3,4-dimethoxycinamoyl anthranilic acid): a novel inhibitor of
      invasion-stimulating interaction between gastric cancer cells and orthotopic
      fibroblasts.
AB  - BACKGROUND: Fibroblasts produce various cytokines that affect the invasion
      ability of cancer cells. We have previously reported that gastric fibroblasts
      play an important role in the metastatic process of gastric cancer. Tranilast is
      a clinical drug for inhibition of fibroblast growth. To develop a drug for cancer
      invasion, the effect of Tranilast on the invasion-stimulating interaction was
      examined. MATERIALS AND METHODS: The human gastric carcinoma cell line, OCUM-2D,
      and the gastric fibroblast cell line, NF-10, were used. The effect of Tranilast
      on the invasion ability of OCUM-2D cells with NF-10 cells was examined by
      invasion assay. RESULTS: The invasion ability of OCUM-2D cells was significantly
      increased by co-culturing with NF-10 cells (p < 0.01). Tranilast, at
      concentrations of more than 0.01 mM, significantly suppressed the invasion
      ability of OCUM-2D cells co-cultured with NF-10 cells. Tranilast decreased matrix
      metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-beta 1)
      production from fibroblasts. TGF-beta 1 enhanced the MMP-2 production from
      fibroblasts. The invasion ability of gastric cancer cells was increased by MMP-2
      and TGF-beta 1 from fibroblasts and this effect was inhibited by Tranilast, which
      decreased the MMP-2 and TGF-beta 1 production from fibroblasts. CONCLUSION:
      Tranilast may be a promising new drug for preventing the metastasis of gastric
      cancer.

PMID- 14666695
TI  - Polyunsaturated fatty acids induce cell death in YAC-1 lymphoma by a caspase-3
      independent mechanism.
AB  - BACKGROUND: The involvement of certain fatty acids in the induction of apoptosis
      has been established recently. In fact, considerable attention has been given in
      the past few years to the participation of polyunsaturated fatty acids as
      substances capable of modulating tumor cell growth. MATERIALS AND METHODS: Fatty
      acids such as eicosapentaenoic acid (EPA), linolenic acid (LNA), arachidonic acid
      (AA), linoleic acid (LA), oleic acid (OA) or stearic acid (SA) were added to YAC
      1 tumor cells. RESULTS: Incubation of cells with fatty acids revealed a loss of
      cell viability in a dose-dependent manner. Quantification of DNA fragmentation
      showed a significant increase particularly in cells treated in the presence of
      LA, whereas the accumulation of triacylglycerols in the form of cytoplasmic lipid
      droplets was significantly enhanced in cells cultured with EPA, LNA or AA. The
      production of reactive oxygen species (ROS) was substantially increased after
      cell incubation. Nevertheless, the analysis of caspase-3 activity indicated a
      relevant increase in cells cultured in the presence of LA, OA or SA, but not in
      cells cultured with EPA, LNA or AA. CONCLUSION: On the basis of these results, we
      can speculate that long-chain polyunsaturated fatty acids such as EPA and AA as
      well as LNA induce cell death in YAC-1 lymphoma by an independent mechanism of
      caspase-3 activation.

PMID- 14666696
TI  - Multiple squamous cell carcinomas of the head and neck show different phenotypes
      of allelic loss patterns suggesting different clonal origin of carcinogenesis.
AB  - BACKGROUND: Multiple squamous cell carcinomas in the head and neck are not such a
      rare phenomenon in patients. To examine if these tumors have the same genetic
      basis or not, we investigated genetic alterations such as allelic loss in such
      multiple tumors to see if they showed identical patterns. MATERIALS AND METHODS:
      Patterns of the loss of heterozygosity at 3p, 9p and 17p loci were analyzed in
      multiple head and neck squamous cell carcinomas of the same patient. RESULTS:
      Metachronous laryngeal and tongue tumors of a patient were found to have
      identical patterns of allelic loss, while synchronous tumors of three other
      patients had different patterns of such loss. CONCLUSION: Our data support the
      idea that field carcinogenesis caused by exposure of oral, laryngeal and
      pharyngeal mucosa to carcinogens may lead to the independent development of
      synchronous non-related tumors at different sites of the upper aerodigestive
      tract.

PMID- 14666697
TI  - Migration and invasion of human prostate cancer cells is related to expression of
      VEGF and its receptors.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors are
      becoming of increasing interest as major regulators of cancer cell growth and
      metastases. VEGF is expressed by many cancer cells including most prostatic
      carcinomas. Recently it has also been shown that the VEGF receptors are also
      expressed by prostate cancer cells and it has been suggested that there may be
      autocrine regulatory loops that are important in the development and progression
      of the disease. To date, however, there have only been descriptive studies of
      expression without correlation of the findings with possible pathophysiologic
      effects. The present studies were done to determine if there is a correlation
      between expression of VEGF receptors and the ability of human prostate cancer
      cells to invade and migrate in vitro. MATERIALS AND METHODS: Using RT-PCR we
      examined the expression of VEGF and its receptors, KDR, Flt-1, NP-1 and NP-2, in
      8 human prostate cancer cell lines and then correlated the expression patterns
      with the ability of these cell lines to invade and migrate through membranes in a
      modified Boyden Chamber assay in the presence and absence of VEGF. RESULTS: Six
      of the 8 cell lines expressed VEGF. None expressed the Flt-1 receptor and only 2
      expressed KDR. The most commonly expressed VEGF receptor was NP-1 (5 of 8 cell
      lines) and its expression was strongly, and negatively, correlated with the
      ability of these cell lines to invade and migrate in the assay system used. Cell
      lines expressing NP-1 had low levels of migration both with and without VEGF
      compared to those not expressing NP-1. CONCLUSION: These studies suggest that
      variable expression of VEGF receptors in prostate cancer, particularly NP-1, may
      have important consequences for cell growth, invasion and metastases in this
      disease.

PMID- 14666698
TI  - Effect of cyclooxygenase-2 (COX-2) inhibitors on prostate cancer cell
      proliferation.
AB  - BACKGROUND: The tricyclic cyclooxygenase-2 (COX-2) inhibitors celecoxib and
      rofecoxib exhibit different magnitudes of antiproliferative activity against the
      human prostate cancer cell lines LNCaP and PC-3. We investigated the correlation
      between the COX-2 inhibitory potencies, antiproliferative activities and the
      nature of the central ring system of novel tricyclic COX-2 inhibitors belonging
      to the diarylcycloalkyl and diarylheterocyclic classes possessing a central 3
      membered cyclopropyl (1 and 2), a 5-membered isoxazoline (3), an isoxazole (4) or
      2-(5H) furanone (5), and a 6-membered pyran-2-one (6a-c) ring system. MATERIALS
      AND METHODS: Novel tricyclics were synthesized and evaluated in vitro for their
      COX-1/COX-2 inhibitory activities and their abilities to inhibit cell
      proliferation in prostate (AT3B-1, PC-3 and LNCaP) and breast (MCF-7) cancer cell
      lines. A molecular modeling study was carried out to characterize the electronic
      nature of the central ring systems of the novel tricyclic COX-2 inhibitors.
      RESULTS: The isoxazoline (3), which exhibited excellent COX-2 inhibitory potency
      and selectivity, showed growth inhibition in all the cell lines tested with IC50
      values of 349 microM (AT3B-1), 378 microM (PC-3), 100 microM (LNCaP) and 200
      microM (MCF-7), respectively. The rofecoxib analog (5) and 6-membered pyran-2
      ones (6a-c) showed weak inhibition (MCF-7, AT3-B-1 and PC-3) inspite of
      possessing good COX-2 inhibitory potencies and selectivities. CONCLUSION: This
      study demonstrates that the antiproliferative activity profiles exhibited by the
      novel tricyclic COX-2 inhibitors is dependent on the electronic nature of the
      central ring system and is independent of their COX-2 inhibitory potencies and
      selectivities. Accordingly, the 2,3-dimethyl-5-(4-methylsulfonylphenyl)-4-phenyl
      4-isoxazoline (3), which possesses an electron rich central 5-membered isoxazole
      ring, could serve as a lead compound to develop novel drugs to treat prostate
      cancer.

PMID- 14666699
TI  - Deregulation of D-type cyclins in uterine cancers. Cyclin D1/D3 is differentially
      expressed in cervical cancer.
AB  - BACKGROUND: We have previously found cyclin D1 to be overexpressed in 45% of
      corpus cancers, but in only 3% of cervical cancers. To see whether and how D-type
      cyclins contribute to the neoplastic phenotype in uterine cancers, aberrant
      expression and association between cyclins D1 and D3 proteins were studied.
      MATERIALS AND METHODS: Expression of cyclin D3 was investigated by
      immunohistochemistry in 51 patients with primary cancer of the corpus and 73
      cases of primary cervical carcinomas. Amplification of the cyclin D1 and D3 genes
      was investigated by fluorescence in situ hybridisation (FISH). RESULTS: We found
      high/moderate levels of cyclin D3 in 53.5% of cervical cancers and 55% of corpus
      cancers. High/moderate expression of cyclin D1 and D3 was associated in the
      corpus cancers, but not in cervical cancers. The accumulation of cyclin D3 but
      not D1 protein could, in some cases, be explained by increased gene dosage since
      extra copies of chromosome 6 were found. CONCLUSION: This study demonstrates that
      in cervical cancers cyclin D3 may compensate for low levels of cyclin D1, whereas
      in corpus cancers both isoforms may contribute to the neoplastic phenotype.

PMID- 14666700
TI  - Expression of MMP-2, MMP-7, MMP-9, MMP-10 and MMP-11 in human astrocytic and
      oligodendroglial gliomas.
AB  - The members of the matrix metalloproteinase family (MMP) have the ability to
      degrade macromolecules of the extracellular matrix and are responsible for tumor
      invasion and infiltration, limiting the effectiveness of the neurosurgical
      resection of brain tumors. Among the glial brain tumors, astrocytomas and
      oligodendrogliomas are the most important tumor entities and require a different
      therapeutic approach. To determine the pattern of MMP expression in astrocytic
      and oligodendroglial tumors, sections of astrocytic and oligodendroglial
      differentiated glioblastomas (WHO grade IV), as well as of anaplastic
      oligodendrogliomas (WHO grade III) and anaplastic gemistocytic astrocytomas (WHO
      grade III) were immunostained for MMP-2, MMP-7, MMP-9, MMP-10 and MMP-11. MMP-7,
      MMP-10 and MMP-11 were strongly expressed by neoplastic gemistocytic astrocytes
      while oligodendrocytic tumor regions showed only a low immunoreaction. In
      contrast, MMP-2 and MMP-9 mainly immunolabeled vascular structures. These data
      indicated that MMP-7, MMP-10 and MMP-11 contribute to the worse prognosis of
      astrocytic tumors when compared to oligodendrogliomas, while MMP-2 and MMP-9
      might play an important role in neo-angiogenesis and tumor vascularization.

PMID- 14666701
TI  - Expression of p63 mRNA isoforms in normal human tissue.
AB  - This report describes the presence of different p63 isoforms in normal human
      tissue. The p63, expressed by basal cells of stratified epithelia and
      myoepithelial cells, is characterized by different mRNA isoforms formed by
      alternative splicing. Three isoforms were shown to act pro-apoptotically, while
      the remaining three isoforms are anti-apoptotic. Therefore a shift in a balance
      between different p63 isoforms might promote or inhibit normal and malignant
      growth. Our results show that in bone marrow, brain, colon, skeletal muscle,
      spleen and testis only pro-apoptotic p63 isoforms are expressed, whereas only
      anti-apoptotic isoforms are present in lung, placenta and salivary gland. In
      kidney, prostate, skin, thymus, trachea and uterus both variants are present.
      Presented results will allow in the future to compare p63 isoforms in various
      pathological processes with normal tissue pattern in order to evaluate the
      contribution of p63 isoform imbalance to the pathophysiology of various malignant
      diseases.

PMID- 14666702
TI  - HMG CoA reductase inhibitor fluvastatin arrests the development of implanted
      hepatocarcinoma in rats.
AB  - BACKGROUND: Fluvastain (Flu) is widely accepted to have anticancer effect
      although its in vivo chemopreventive ability in cancer has not been studied. The
      therapeutic and chemopreventive effects of Flu were compared in vivo in the
      present study. MATERIALS AND METHODS: Under the left renal capsule of FLF1 hybrid
      rats 10(6) hepatocarcinoma cells were implanted (He/De14) on sponge disc. The
      differences in net weight between the left and right kidneys were determined as
      tumor weights. Flu was administered per os in 0.5, 2 and 20 mg/kg/day doses.
      RESULTS: The 21-day pretreatment before tumor implantation with Flu had no effect
      on tumor development in the absence of Flu treatment after the implantation. The
      addition of Flu before and after tumor implantation demonstrated a more intensive
      anticancer effect than in the case of treatment given only after tumor
      implantation. CONCLUSION: Flu has in 0.5-20 mg/kg/day doses a therapeutic and
      also a preventive effect on hepatocarcinoma growth in rats depending on the type
      of administration.

PMID- 14666703
TI  - Synthesis and in vitro evaluation of the phenylboric acid derivative entrapped
      lipiodol in boron neutron capture therapy for hepatoma.
AB  - BACKGROUND: Hepatoma, a common cancer in Taiwan, responds poorly to conventional
      therapies. Boron neutron capture therapy (BNCT) may provide a promising approach
      for hepatoma therapy. In this study, a pharmaceutical composition, phenylboric
      acid derivative entrapped lipiodol (PBAD-lipiodol), was synthesized and
      characterized. In vitro study was used for evaluation of PBAD-lipiodol for the
      BNCT of hepatoma. MATERIALS AND METHODS: alpha Track observation was used to
      identify the boron compound in the TLC plate and to evidence the uniform
      distribution of boron in the PBAD-lipiodol. Inductively coupled plasma-atomic
      emission spectroscopy and neutron activation analysis were used to determine the
      concentrations of boron and lipiodol, respectively. Human hepatoma HepG2 cells
      were used for in vitro experiments. A Nomarski optical microscope was used to
      investigate the uptake of PBAD-lipiodol globules in individual hepatoma cells.
      RESULTS: PBAD-lipiodol was stable in human serum. The boron source, PBAD, was
      uniformly distributed in PBAD-lipiodol. Many of the PBAD-lipiodol globules were
      internalized and retained in HepG2 cells, and the boron concentration of HepG2
      cells reached 269 ppm after 72 hours of PBAD-lipiodol treatment. CONCLUSION: In
      vitro studies revealed that PBAD-lipiodol could deliver a therapeutically
      effective amount of PBAD as a boron source for the BNCT of hepatoma. PBAD
      lipiodol is a potential new boron drug for the BNCT of hepatoma.

PMID- 14666704
TI  - Ki-S1--a prognostic marker for hypopharyngeal carcinoma with potential predictive
      value for response to chemotherapy.
AB  - BACKGROUND: It has previously been shown that the proliferative activity,
      determined by means of the monoclonal antibody Ki-S11 against the Ki-67 protein,
      is a significant prognostic factor for squamous cell carcinoma of the hypopharynx
      (SCCH). We now investigated the prognostic and the predictive impact of Ki-S1, a
      monoclonal antibody which detects an epitope of topoisomerase II alpha, another
      proliferation-associated antigen. MATERIALS AND METHODS: The proliferation index
      (PI) in terms of Ki-S1 immunolabeling was evaluated on tumor specimens from 131
      patients with SCCH. Survival probabilities over an observation time of 72 months
      were calculated by Kaplan-Meier analysis. RESULTS: Patients with low PI (< or =
      45%) had a significantly improved 5-year survival (33.2%) compared with patients
      with high PI (> 45%), of whom only 11% survived after 5 years (p = 0.001). Since
      there was no significant difference between the results obtained with Ki-S1 and
      Ki-S11, the present data confirm the prognostic significance of the proliferative
      activity in SCCH. CONCLUSION: Topoisomerase II alpha is also the target of many
      antineoplastic drugs and it has been proposed that its expression in tumor cells
      correlates with chemosensitivity. The high average topoisomerase II alpha content
      in SCCH therefore promises a good responsiveness to topoisomerase inhibitors.
      Because Ki-S1 directly measures cellular topoisomerase II alpha expression, it
      might be exploited not only as a prognostic indicator but also as a predictive
      marker for patients with SCCH.

PMID- 14666705
TI  - Distinct site-specific oncoprotein overexpression in head and neck squamous cell
      carcinoma: a tissue microarray analysis.
AB  - BACKGROUND: Tissue microarray (TMA) analysis is a high-throughput approach that
      allows the screening of large tumor collectives for cytogenetic aberrrations. In
      this study, a TMA of a large collection of clinically well-defined primary
      squamous cell carcinomas of the head and neck (HNSCC) was used to determine the
      expression of several oncoproteins. MATERIALS AND METHODS: A TMA containing 547
      primary HNSCC was used for the analysis of cyclinD1, c-myc, erbb1 and erbb2
      expression by immunohistochemistry (IHC). RESULTS: CyclinD1 and c-myc were
      overexpressed at higher frequencies in primary pharyngeal and laryngeal
      carcinomas compared with primary oral carcinomas (p < 0.001 and p < 0.001), while
      erbb1 and erbb2 overexpression was associated with oral site (p < 0.001 and p =
      0.04, respectively). Furthermore, cyclinD1 overexpression correlated with stage
      IV primary carcinomas (p = 0.04). CONCLUSION: HNSCC is a heterogenous group of
      tumors, which, depending on anatomic sites and clinical stage, shows variable
      expressions of the oncoproteins described. This indicates a specific pathogenic
      role of these oncoproteins in different subtypes of HNSCC and may have
      therapeutic implications.

PMID- 14666706
TI  - Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human
      tumour xenografts.
AB  - BACKGROUND: RH1 and MeDZQ represent novel aziridinylbenzoquinones that can be
      activated by DT-diaphorase to form unique DNA lesions. RH1 is due to enter a
      phase 1 clinical trial in the United Kingdom in the summer of 2003, where
      pharmacodynamic monitoring of DT-diaphorase will be performed. MATERIALS AND
      METHODS: The antitumour efficacy of RH1 and MeDZQ has been studied in 4 human
      xenografts (3 non-small cell lung cancer and 1 colon cancer), and compared to the
      level of constitutive DT-Diaphorase activity measured by the DCPIP assay.
      RESULTS: The 4 xenografts exhibited a wide range of DT-diaphorase activity (4.8
      303 nmol/min/mg). Greater antitumour activity was recorded in the xenografts
      expressing high levels of DT-diaphorase (e.g. NX002, DT-diaphorase activity, 303
      +/- 52 nmol/min/mg, T/C to MeDZQ, 33.3% and to RH1, 43.4%). CONCLUSION: These
      data add in vivo support to a role for DT-Diaphorase in the antitumour activity
      of RH1.

PMID- 14666707
TI  - The role of hyaluronan in mesothelium-induced motility of ovarian carcinoma
      cells.
AB  - BACKGROUND: Ovarian carcinoma metastases occur when the malignant cells establish
      new colonies on the peritoneal surface. This study was undertaken to determine
      whether mesothelial cell hyaluronan affects tumor cell motility. MATERIALS AND
      METHODS: Four ovarian carcinoma cell lines (UCI 101, UCI 107, OC 222 and
      NIH:OVCAR-3) were allowed to migrate toward cultures of mesothelial cells and
      different concentrations of hyaluronan. Mesothelial hyaluronan production in the
      presence of the ovarian carcinoma cells was assayed. RESULTS: The carcinoma lines
      showed greater motility toward mesothelial cells than controls, but the increased
      motility was abolished by hyaluronidase. Co-cultures of mesothelial cells and
      ovarian carcinoma cell lines produced up to twice as much hyaluronan as
      mesothelial cells alone. Purified hyaluronan induced dose-dependent and
      chemotactic motility in all carcinoma lines. CONCLUSION: These results are
      evidence that mesothelial hyaluronan is a potential paracrine motility factor for
      ovarian carcinoma. The presence of mesothelial cells on the peritoneal cavity may
      encourage the establishment of ovarian carcinoma metastases.

PMID- 14666708
TI  - Detection of circulating prostate cells during radical prostatectomy by
      standardized PSMA RT-PCR: association with positive lymph nodes and high
      malignant grade.
AB  - BACKGROUND: The purpose of this study was to establish a quantitative
      standardized RT-PCR for the detection of Prostate Specific Membrane Antigen
      (PSMA)-expressing circulating cells and to evaluate clinical relevance in
      patients undergoing radical retropubic prostatectomy (RRP) for clinically
      localized prostate cancer (PCa). MATERIALS AND METHODS: An external standard
      molecule (PSMA MIMIC) was constructed for standardization of PSMA RT-PCR
      reactions. It has the same sequence as endogenous PSMA, except for a central 85
      bp deletion, allowing the amplification of both targets simultaneously with
      nearly the same amplification characteristics as in a nested PCR. PSMA RT-PCR was
      performed from peripheral blood samples of 73 patients with clinically localized
      PCa, 4 with metastatic PCa, 27 with benign prostatic hyperplasia (BPH) and 27
      controls. Pre, intra- and postoperative blood samples were tested for circulating
      PSMA expressing cells in 54 out of 73 patients with clinically localized PCa. We
      also tested intraoperative blood samples of 19 BPH patients treated by
      transurethral or open surgery. RESULTS: Endogenous PSMA signals from PCa patients
      varied between 850 and 9900 transcript molecules, corresponding to 2-20 PSMA
      expressing cells/ml blood. Standardized RT-PCR using the PSMA MIMIC molecule
      revealed a significant decrease of "false-positives" in cancer-free controls (p =
      0.004). Controls could clearly be distinguished from prostate cancer patients
      based on PSMA PCR positivity (p = 0.003). Thirty-two % of patients with localized
      prostate cancer, 11% of BPH patients and 7% of healthy controls were positive in
      standardized assays compared to 48%, 30% and 27% without PSMA MIMIC,
      respectively. Preoperatively, a correlation with tumor stage (p = 0.030), grade
      (p = 0.035) and Gleason Score (p = 0.03) could be demonstrated in clinically
      localized PCa patients. Dissemination of prostate cells during surgery occurred
      in 32% of the RRPs and 21% of BPH patients. Positive PCR signals from
      intraoperative blood samples correlated with positive lymph node status (p =
      0.007) and tumor grade (p = 0.005). Postoperative positive results correlated
      with grade (p = 0.012) and Gleason Score (p = 0.035). CONCLUSION: Counseling the
      patient with clinically localized prostate cancer can be challenging. Surgery may
      be, in retrospect, inappropriate in a number of patients due to preoperative
      understaging. This newly constructed external standard allows quantitative
      detection of circulating prostate cells, and therefore may open new perspectives
      for PSMA RT-PCR techniques as diagnostic assays and tools for post-therapeutic
      follow-up.

PMID- 14666709
TI  - Protein kinase C eta is associated with progression of renal cell carcinoma
      (RCC).
AB  - BACKGROUND: The expression of all eleven PKC-isoforms in clear cell RCCs (ccRCC)
      and in the corresponding normal renal tissue was quantified. A possible
      association of PKC-isoforms with histopathological parameters was examined.
      MATERIALS AND METHODS: Proteins were isolated from tumor and normal tissue of 43
      patients with ccRCC. Expression of PKC-isoforms were quantified by Western blot
      analysis. RESULTS: In both, ccRCCs and the corresponding normal renal tissue, all
      PKC-isoforms apart from PKC gamma and theta were detectable. Striking
      associations between PKC-isoforms and histopathological parameters were observed:
      (i) a 3-fold increase in PKC eta of grade 3 and 4 versus grade 1 and 2 tumors (p
      = 0.025), (ii) a decrease of PKC alpha in tumor versus normal tissue of 18% (p =
      0.020) and (iii) a 20% increase of PKC zeta in grade 3 and 4 versus grade 1 and 2
      tumors (p = 0.092). CONCLUSION: The major result is a clear correlation of PKC
      eta expression with tumor progression. This observation-is in agreement with the
      known oncogenic properties of PKC eta. Similarly, oncogenic PKC zeta also
      increased with tumor progression. PKC alpha, with known tumor-suppressor
      properties, was decreased in ccRCC versus normal tissue. These findings may
      become important for both classification and treatment of ccRCC.

PMID- 14666710
TI  - Mimosine, a plant-derived amino acid induces apoptosis in human pancreatic cancer
      xenografts.
AB  - BACKGROUND: Several studies have indicated that mimosine, a plant amino acid, is
      a potential inhibitor of the cell cycle giving rise to growth arrest in G1-phase.
      These results were mainly derived from in vitro investigations. To date only one
      paper is available about its applicability in xenografted lung tumor. This study
      revealed a tumor growth suppression and an increased apoptotic index. Our
      experiment was aimed at investigating the influence of mimosine in human
      pancreatic cancer. MATERIALS AND METHODS: Subcutaneously growing human pancreatic
      cancer xenografts in immunosuppressed mice were treated with 30 mg/kg b.w.
      mimosine for 34 days and the apoptosis was assessed by flow cytometry. RESULTS:
      Mimosine treatment resulted in a significant tumor growth suppression and the sub
      G1 fraction was doubled (10.82 +/- 1.18% vs. 4.65 +/- 1.65 % in controls, p <
      0.01). CONCLUSION: This is the first evidence that mimosine exerts an apoptotic
      activity in xenotransplanted human pancreatic cancer and suppresses its growth.

PMID- 14666712
TI  - Cytokines and Epstein Barr virus (EBV) genes expression in blood chronic
      lymphocytic leukaemia (CLL) cells and their immortalised CLL cell lines.
AB  - We have encountered two unique chronic lymphocytic leukaemia (CLL) patients, PG
      and NN. Some blood CLL cells of these patients have been infected and carry
      Epstein Barr virus (EBV) in vivo. In spite of their early-activated G0/G1 stage
      of post germinal center (GC) memory cells, ex vivo EBV-carrying blood CLL cells
      of PG clone expressed LMPs and used specific QUK splice for their EBNA1
      expression, similar to the EBV-carrying cells of non-B origin. Interestingly, EBV
      carrying CLL cells of NN clone expressed LMP2a and used UK-splice for their EBNA1
      expression, similar to the in vivo EBV-carrying high density normal B cells in
      the blood of healthy individuals. The CLL-derived lines but not normal
      lymphoblastoid cell line (LCL) used QUK- and YUK-splice for their EBNA1
      expression. As expected, LCL and their permanent CLL-derived lines used Cp
      promoter and up-regulated their EBNA2 expression. Blood CLL cells and the CLL
      derived cell lines of these patients spontaneously produced cytokines as shown by
      microarray assay. The types and quantities of cytokines might relate to their CLL
      origin and viral strain in the given CLL cells. Neither blood CLL nor their CLL
      derived cell lines express any detectable apoptosis-inducer ligands, CD95L or Apo
      3L. As a consequence of cell cycle progression, CLL-derived cell lines up
      regulated their co-stimulator molecules CD80 and apoptosis-related receptor CD95.
      Since only the rare EBV-carrying CLL cells grew in vitro, the combination of
      viral genome and cytokines seems to be critical for the outgrowth of EBV-carrying
      CLL cells over their EBV-negative counterpart in vitro but not in vivo.

PMID- 14666711
TI  - Assessing optimal promoter activity for constructs in gastrointestinal gene
      therapy.
AB  - BACKGROUND: During recent decades, studies of various cancer-related genes has
      led to a growing understanding of molecular mechanisms of gastrointestinal cancer
      resulting in a genetic progression model. Nevertheless, with a few exceptions,
      our knowledge of participating genes has not been exploited for gene therapeutic
      approaches. Therefore, we monitored the promoter activity of genes shown to be
      significantly expressed in gastrointestinal tumors to select optimally active
      promoters for recombinant DNA constructs. Such molecules will contain a suicide
      gene under a suitable cell type-specific regulatory element. MATERIALS AND
      METHODS: Using promoter-reporter gene (luciferase) constructs we compared the
      activities of KRT19, TFF1, SEL1L, MUC4, MUC1, CEL and hTERT by transfecting them
      into the gastrointestinal cell lines MKN45 and DAN-G for transient expression.
      Furthermore we tested the endogenous expression of these genes by RT-PCR.
      RESULTS: From a selection of 9 promoter constructs SEL1L, KRT19 and MUC1
      displayed the highest activity levels while others were moderately expressed.
      CONCLUSION: These three appear the most capable ones to drive suicide genes, like
      thymidine kinase or cytosine deaminase, a study presently initiated.

PMID- 14666713
TI  - Immunohistochemical determination of vascular endothelial growth factor (VEGF)
      overexpression in malignant melanoma.
AB  - BACKGROUND: Molecular changes associated with the transition of melanoma cells
      from radial to vertical growth phase are not defined. To evaluate the role of
      VEGF in melanogenesis and determine its possible diagnostic and prognostic
      implications, we analyzed overexpression of VEGF in 202 cases of melanoma.
      MATERIALS AND METHODS: Overexpression of VEGF was evaluated in 202 archival
      paraffin-embedded tissue specimens using an avidin-biotin immunohistochemical
      (IHC) assay. RESULTS: Of the 202 melanoma specimens, 42 (20.8%) showed evidence
      of VEGF overexpression on IHC testing. Multivariate analysis performed using Cox
      proportional hazards method did not show a statistically significant survival
      difference between the VEGF-positive and negative groups (p = 0.25). CONCLUSION:
      Although of no significant prognostic value, VEGF may have critical therapeutic
      implications as a molecular target since it is expressed in about 20% of
      melanomas. The role of target-specific therapies against VEGF in malignant
      melanoma warrants further investigations.

PMID- 14666714
TI  - Different basal expression of type T1 and T2 cytokines in peripheral lymphocytes
      of patients with adenocarcinomas and benign hyperplasia of the prostate.
AB  - BACKGROUND: It has been proposed that a reduced immunological competence and a
      dysregulation in the T1/T2 balance may be implicated in the development of
      cancer. In order to study the immunological situation in vivo, we compared the
      mRNA expression of the T1 cytokine IFN-gamma and the T2 cytokine IL-10 in freshly
      isolated, not in vitro stimulated, peripheral blood lymphocytes from patients
      with localized prostate carcinomas (PCa) and benign prostate hyperplasia (BPH).
      MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by
      gradient centrifugation. CD4(+)- and CD8(+)-lymphocytes were selected with
      magnetic beads against these determinants. In these lymphocyte preparations, mRNA
      expression of IL-10 and IFN-gamma was determined by using a semiquantitative RT
      PCR, standardized to the beta-actin expression. RESULTS: In the PBMC from 35
      patients with localized PCa a significantly lower expression of IFN-gamma and IL
      10 was found, compared to 28 patients with BPH. Cytokine expression also was
      lower in the isolated CD4(+)- and CD8(+)-lymphocytes of the carcinoma patients.
      However, the difference was statistically significant only for IL-10. CONCLUSION:
      Our data reflect a reduced basal cytokine expression in peripheral lymphocytes of
      patients with localized PCa compared to BPH. Since the T2 response was more
      strongly reduced than T1, there seems to be a decreased immune activation, but a
      relative T1 dominant cytokine pattern in the cancer patients.

PMID- 14666715
TI  - Extracellular matrix proteins modulate cytokine production by monocytes during
      their interactions with cancer cells.
AB  - BACKGROUND: This study examined the role of extracellular matrix compounds (EMC)
      in the alteration of tumour necrosis factor-alpha (TNF alpha) and interleukin-10
      (IL-10) production by human monocytes stimulated with cancer cells. MATERIALS AND
      METHODS: Monocytes were cultured with cancer cells in the absence or presence of
      EMC and cytokine release was measured by ELISA. In some experiments monocytes
      preincubated with monoclonal antibodies (mAbs) against CD29 and CD44 were used.
      RESULTS: Fibronectin, collagen type I and type IV induced production of cytokines
      by monocytes and mAbs inhibited this effect. The release of TNF alpha monocytes
      stimulated with cancer cells was inhibited by fibronectin, collagen type I and IV
      and IL-10 by fibronectin and collagen type IV. Other EMC were ineffective. Both
      mAbs partly reversed this inhibitory effect. CONCLUSION: These findings suggest
      that some EMC induced cytokine release by monocytes but inhibit monocyte-cancer
      cell interactions and this effect is presumably due to competition for the same
      receptors.

PMID- 14666716
TI  - Combined effects of resveratrol and paclitaxel on lung cancer cells.
AB  - Resveratrol (3,4',5-trihydroxystilbene) is a phytoalexin found in grapes and
      other food products that can prevent cancer. We studied the in vitro biological
      activity of this compound by examining its effect on proliferation and inducing
      apoptosis in three lung cancer cell lines (A549, EBC-1, Lu65). Resveratrol
      inhibited the growth of A549, EBC-1 and Lu65 lung cancer cells by 50% (ED50) at
      concentrations between 5-10 microM. We also examined the combined effects in
      these cells of resveratrol and paclitaxel, an essential chemotherapeutic agent
      against lung cancer. Although simultaneous exposure to resveratrol plus
      paclitaxel did not result in significant synergy, resveratrol (10 microM, 3 days)
      significantly enhanced the subsequent antiproliferative effect of paclitaxel. In
      addition, resveratrol as well as paclitaxel induced apoptosis in EBC-1 and Lu65
      cells, as measured by TUNEL and caspase assays, as well as flow cytometry.
      Resveratrol (10 microM, 3 days) similarly enhanced the subsequent apoptotic
      effects of paclitaxel. We examined the effects of resveratrol and paclitaxel on
      levels of p21waf1, p27kip1, E-cadherin, EGFR and Bcl-2 in EBC-1 cells.
      Resveratrol (10 microM, 3 days) prior to paclitaxel induced p21waf1 expression
      approximately 4-fold. These results suggest that resveratrol may be a promising
      alternative therapy for lung cancer and that lung cancer cells exposed to
      resveratrol have a lowered threshold for killing by paclitaxel.

PMID- 14666717
TI  - Multimodal approach and its impact on survival for patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: There are few studies evaluating the prognostic impact on survival of
      treatment strategy in patients with hepatocellular carcinoma (HCC). The aim of
      this study was to analyse whether a multimodal approach, that represents a
      synergic association of different therapeutic procedures, may improve survival of
      patients with HCC. PATIENTS AND METHODS: Two hundred and fourteen patients with
      HCC were enrolled in the study. The multimodal approach was chosen for 27 out of
      106 (25%) non surgical patients, 42 out of 81 (52%) patients who underwent liver
      resection and 19 out of 27 (70%) patients who underwent liver transplantation.
      RESULTS: The long-term survival of patients who underwent the multimodal approach
      improved significantly with respect to patients treated by both resection and
      other therapies alone. The 5-year survival rates were 52% vs. 11% (p < 0.05) in
      the non surgical group and 40% vs. 24% (p < 0.05) in the resection group when a
      multimodal approach was used for the treatment of recurrences. In patients with
      advanced HCC undergoing liver transplantation, multimodal treatment resulted in
      long-term survival comparable to that of patients with early HCC. CONCLUSION: A
      multimodal approach should be suggested in all patients with HCC, since a careful
      integration of surgical and non surgical treatments may improve long-term
      survival in such patients.

PMID- 14666718
TI  - Unexpected interactions between nicotinamide and CPT-11 in a rhabdomyosarcoma
      tumor model.
AB  - We investigated the potential chemosensitizing effect of nicotinamide on CPT-11,
      and the relationship between nicotinamide and CPT-11, intratumoral drug uptake in
      syngeneic rhabdomyosarcoma tumors in rats. Pretreatment with nicotinamide, known
      to improve tumor oxygenation, perfusion and radiotherapy effect, only caused a
      minor increase in tumor growth delay. To our surprise, intratumoral uptake of CPT
      11 and its active metabolite SN-38 decreased significantly between 19% and 43%.
      This discrepancy suggests that the potential chemosensitizing effect of
      nicotinamide, seen in other studies, is based on a direct effect on tumor cells
      rather than on an increased delivery of anticancer drugs. A second finding is
      that plasma levels of CPT-11 and SN-38 respectively increase and decrease after
      nicotinamide exposure, suggesting inhibition of carboxylesterase, which is
      necessary for the conversion of CPT-11 to its active metabolite SN-38. Great care
      is required when combining nicotinamide with anticancer drugs, since unexpected
      pharmacokinetic and pharmacodynamic alterations might occur.

PMID- 14666719
TI  - The antitumor activity of the somatostatin structural derivative (TT-232) on
      different human tumor xenografts.
AB  - A somatostatin structural derivative (TT-232) has been developed in our
      laboratory with strong antiproliferative effect but no GH- release inhibitory
      activity. TT-232 inhibited tyrosine kinase activity of tumor cells lines and this
      inhibition correlated well with the inhibition of cell proliferation. The
      antineoplastic activity of TT-232 has been found to be associated with induction
      of programmed cell death (apoptosis) in tumor cell, resulting in highly selective
      elimination of neoplastic tissue. The aim of this study was the therapeutic
      efficacy of TT-232 on different human models: PC-3 prostate carcinoma, MDA-MB-231
      (ER-) and MCF-7 (ER+) breast carcinoma, HT-29 colon carcinoma, HT-18 melanoma, HL
      60 promyelocytic leukemia. We studied the therapeutic efficacy of the novel
      somatostatin analog, it for 30 days with intermittent injection once daily and
      for 14 days with s.c. infusion using the Alzet osmotic minipump (model 2002). The
      antitumor activity of TT-232 was evaluated on the basis of survival time and
      tumor growth inhibition. The tumor growth inhibitory effect of TT-232 on human
      tumor xenografts proved to be significant, resulting in 30%-80% decrease in tumor
      volume and in 20-60% tumor free animals. This antitumor efficacy of the novel
      somatostatin analog was observable in almost all tumors investigated. These data
      suggest that the novel somatostatin analog (TT-232) is an effective and promising
      antitumor agent.

PMID- 14666720
TI  - Immunohistochemical determination of HER-2/neu in malignant melanoma.
AB  - BACKGROUND: HER-2/neu onco-protein is increasingly being recognized as a target
      for therapy in solid tumors, but data on its role in malignant melanoma is
      currently limited. Our study objective was to determine a relationship, if any,
      between HER-2/neu overexpression and malignant melanoma. PATIENTS AND METHODS:
      Overexpression of HER-2/neu was evaluated in patients with malignant melanoma by
      using immunchistochemistry (DAKO Hercep test) in 202 archival tissue specimens.
      RESULTS: Between 1991 and 2001, 202 subjects [109 males; (54%) and 93 females;
      (46%)] with malignant melanoma were studied. Interestingly, only 2 of the 202
      patients (0.9%) with biopsy-proven malignant melanoma revealed HER-2/neu
      overexpression. CONCLUSION: The results of our large study indicate that the HER
      2/neu onco-protein neither has a role in melanogenesis nor is a potential target
      for clinical trials with monoclonal antibody therapy. Thus, there is no role for
      HER-2/neu testing in patients with malignant melanoma.

PMID- 14666721
TI  - Phosphatidylinositol-3 kinase-dependent activation of Akt does not correlate with
      either high mitogenicity or cell migration induced by FGF-1.
AB  - FGF-1 is a pleiotropic growth factor that regulates proliferation, migration and
      differentiation of target cells. In pathological situations FGF-1 could have
      oncogenic potential either due to its mitogenic activity or due to formation of
      new blood vessels. FGF-1 exogenously added to cells not only activates specific
      cell surface receptors, but also enters the cytosol and the cell nucleus.
      Although much data concerning FGF-1-induced signal transduction and translocation
      of externally added FGF-1 into the cells are available, it is difficult to
      discriminate between events leading to cell proliferation and to other cellular
      responses. For the purpose of this study, we used primary human fibroblasts (HFb)
      from skin in order to compare the biological effects of FGF-1 in these cells and
      in NIH/3t3 cells. In this paper, we show that FGF-1 is much less mitogenic for
      HFb than for NIH/3T3 cells, with maximal stimulation obtained at a concentration
      one order of magnitude higher than for NIH/3T3 cells. Despite that, FGF-1
      activates Akt kinase in HFb at lower concentrations than in NIH/3T3 cells. This
      activation is PI3-kinase-dependent, which shows that P13-kinase is activated
      upstream of Akt kinase in human fibroblasts. MAP kinases are activated in both
      cell types in a similar manner, but in HFb cells the inhibition of PI3-kinase by
      inhibitor LY294002 leads to activation of MAP kinases, while in NIH/3T3 cells
      this effect does not occur. Translocation of externally added FGF-1 to the
      cytosol/nucleus of HFb cells is similarly efficient as in NIH/3T3 cells. Our
      results show, also, that activation of Akt in HFb cells does not correlate with
      migratory response, since these cells migrate very inefficiently in response to
      FGF-1.

PMID- 14666722
TI  - Tumor-associated macrophage (TAM) infiltration in gastric cancer.
AB  - BACKGROUND: Tumor-associated macrophages (TAMs) are defined as macrophages that
      migrate into the tumor stroma. TAMs are known to directly or indirectly affect
      immune suppression. TAMs have not previously been reported in gastric cancer.
      MATERIALS AND METHODS: Using anti-CD68 antibodies, we immunohistochemically
      evaluated TAM infiltration in 97 gastric cancer patients who underwent tumor
      resection. Furthermore, CD3-zeta chain expression of tumor infiltrating
      lymphocytes (TILs) from the same section was also examined. According to the
      degree of TAM infiltration, 97 patients were divided into two groups (high TAM
      group, more than 200 positive cells; low TAM group, less than 200 positive
      cells). Clarification of the clinicopathological features of TAM-positive gastric
      cancer was attempted. RESULTS: TAM infiltration in the tumor nest ranged from 0
      to 621 cells (average 187). The degree of infiltration positively correlated with
      depth of invasion, nodal status and clinical stage. Patients in the high TAM
      group had lower CD3-zeta expression by TILs than patients in the low TAM group.
      CD3-zeta expression by TILs negatively correlated with infiltration of TAMs (p <
      0.01). Patients with a high TAM count had poorer surgical outcomes than those
      with a low TAM count. CONCLUSION: From the results of the current study, TAM
      infiltration may be used as a prognostic marker in gastric cancer. Negative
      correlation between TAM infiltration and CD3-zeta expression by TILs suggests
      that TAMs may be responsible for the immunological inactivity of T cells in
      gastric cancer.

PMID- 14666723
TI  - Role of toll-like receptors and their adaptors in adjuvant immunotherapy for
      cancer.
AB  - The potentiation of immune responses to tumor-associated antigen (Ag) is a
      pivotal issue in immunotherapy for cancer and thus requires the use of adjuvants,
      which are involved in efficient antibody (Ab) production and killer cell
      induction. The efficacy for tumor regression of a number of adjuvants that have
      been applied to immunotherapy in humans and tumor-bearing animal models has been
      tested without understanding of the function of adjuvants. Recent findings on the
      function of Toll-like receptors (TLRs) and their adaptors facilitated the
      elucidation of the molecular basis of adjuvant activity. TLR signaling was found
      to induce interferons (IFNs), chemokines and proinflammatory cytokines and mature
      dendritic cells (DCs) for enhanced efficiency in antigen presentation. The
      mediators then play a crucial role in the organization of acquired immunity and,
      together with matured DCs, activate cytotoxic T cells (CTL) and NK cells. These
      TLR outputs vary among adjuvants, which may depend on adjuvant-specific selection
      of appropriate sets of TLRs and their adaptors. Here we review how a variety of
      host immune responses are induced by an individual adjuvant to confer an adjuvant
      specific anti-tumor immunity. We elaborate specifically on two adjuvants, BCG
      cell wall skeleton and double-stranded RNA (dsRNA). The former activates TLR2/4
      on DCs and induces tumor-specific CTL allowing general application to patients
      with surgically dissected cancer and improving prognosis, while the latter
      activates TLR3 on DCs to release type 1 IFN that induces tumor cell apoptosis and
      NK-mediated tumor cytotoxicity.

PMID- 14666724
TI  - Immunotherapy and gene therapy of cancer using antibodies or their genes against
      tumor-associated antigens.
AB  - The purpose of this article is to review the current significance of anti-tumor
      associated antigen (TAA) antibodies in the therapy of cancer. Current data
      suggest that antibodies or their genes against TAAs can be used in order to
      increase the tumor specificity of various therapeutic approaches against cancer,
      thereby enhancing the tumoricidal effect of each treatment while reducing the
      side-effects.

PMID- 14666725
TI  - cDNA cloning and sequencing of a novel monoclonal antibody to carcinoembryonic
      antigen and construction of a mouse/human chimeric antibody.
AB  - BACKGROUND: Mouse monoclonal antibody F33-104 recognizes an epitope which is
      present on the carcinoembryonic antigen (CEA) molecule but not on the other CEA
      family member proteins, and which seems to be of potential value for
      immunotherapy of CEA-expressing cancers. However, an inherent problem in its in
      vivo application is the human anti-mouse antibody response. MATERIALS AND
      METHODS: To reduce its immunogenicity in humans, we cloned and sequenced the V
      region genes of heavy and light chains of F33-104 using the reverse transcription
      polymerase chain reaction method, and then constructed a mouse/human chimeric
      antibody, designated Ch F33-104, by fusing the F33-104 VH and V kappa genes to
      human C gamma 1 and C kappa genes, respectively. The resulting Ch F33-104 was
      expressed in non-Ig-producing myeloma cells and characterized for its CEA binding
      specificity and the tumor cell killing activity. RESULTS: Ch F33-104 specifically
      bound to CEA-expressing tumor cells and revealed a potent antibody-dependent cell
      mediated cytotoxicity with human lymphokine-activated killer cells as effectors
      against the CEA-expressing tumor cells. CONCLUSION: This mouse/human chimeric
      antibody could therefore be a candidate for cancer immunotherapy of CEA-positive
      cancers.

PMID- 14666726
TI  - Beneficial effect of macrophage activating agent NK-4 on Thai HIV-infected
      patients.
AB  - BACKGROUND: We examined the effect of NK-4 (4,4'-[3-[2-(1-ethyl-4(1H)
      quinolinylidene) ethylidene] propenylene] bis(-ethylquinolinium iodide)) on the
      clinical course of Thai HIV-infected patients receiving antiretroviral drugs.
      PATIENTS AND METHODS: Twelve subjects with CD4 count < 500/mm3 were enrolled to
      receive 0.5 mg of NK-4 orally once daily for 8 weeks and then twice daily during
      the follow-up. RESULTS: Most patients showed vitality, increased appetite, stable
      body-weight, increased CD4 counts and no serious adverse effects due to viral
      load. We suggest that the increased CD4 counts are due to the macrophage
      activating effect of NK-4. The patients with increased CD4 counts showed lower
      alpha-N-acetylgalactosaminidase (alpha-NaGalase) activity than those with
      decreased CD4 counts. CONCLUSION: These results suggest that the macrophage
      activating agent NK-4, as an inexpensive and safe drug for HIV-infected patients,
      may play a beneficial role in the clinical treatment of HIV-infected patients.

PMID- 14666727
TI  - Tumor-associated macrophages: foe or accomplice of tumors?
AB  - Macrophages are predominantly involved in the immune and inflammatory processes
      of solid tumors. Macrophages infiltrated into a tumor have an ambivalent
      relationship with the tumor, because they are innately very flexible and
      adaptable depending on the microenvironment of the tissue and the tissue-derived
      factors. The relationship between tumor-associated macrophages (TAMs) and a tumor
      is extremely complicated and has not yet been clearly elucidated. Now, the
      reintegration of biological knowledge including immunology, pathology and
      oncology is indispensable for the clinical application of TAMs to cancer therapy.
      In this review, we focus on the range of pro- and anti-tumor functions performed
      by TAMs and outline a new class of cancer therapies that aims at controlling the
      complex functions of TAMs.

PMID- 14666728
TI  - Malignant potential regarding mucin phenotypes and endocrine cell differentiation
      in gastric adenocarcinoma.
AB  - BACKGROUND: This study was designed to define the relationship between the mucin
      phenotype and differentiation in endocrine cells, including their biological
      behavior in gastric adenocarcinoma. MATERIALS AND METHODS: A total of 337 cases
      of solitary gastric adenocarcinoma were studied. The depth of tumor invasion was
      the mucosa in 58 cases, the submucosa in 206 cases and the muscularis propria in
      73 cases. The mucin phenotype was divided into four phenotypes (gastric,
      intestinal, mixed and null types) based on immunohistochemical staining (HGM,
      Muc2 and CD10) and histochemical staining (PCS). Endocrine cells were identified
      by immunohistochemical staining (serotonin, gastrin, pancreatic polypeptide and
      Chromogranin A staining) in order to examine their relationship to mucin
      phenotype. Lymph node metastasis was used as a major indicator of the malignant
      potential. RESULTS: When lymph node metastasis was analyzed for tumors with
      submucosa(sm) or muscularis propria invasion, the incidence was significantly
      higher in the endocrine cell-positive [ECs(+)] group than in the endocrine cell
      negative [ECs(-)] group. Namely, in gastric type, the incidence was 22.7% for the
      ECs(+) group and 0% for the ECs(-) group (p < 0.05). In intestinal type it was
      26.9% for the ECs(+) group and 4.5% for the ECs(-) group (p < 0.05). When the 5
      year survival rate of patients with a depth of sm or mp carcinoma was analyzed in
      relation to the mucin phenotype, no significant difference was seen in the
      survival rate according to the mucin phenotype, but the prognosis tended to be
      less favorable in the ECs(+) group than in the ECs(-) group (p = 0.06).
      CONCLUSION: The expression of endocrine cells was thus found to be more important
      as a prognostic factor than the mucin phenotype.

PMID- 14666729
TI  - Relationships between S-100 protein-positive cells and clinicopathological
      factors in patients with colorectal cancer.
AB  - BACKGROUND: An increased number of dendritic cells (DCs), as indicated by
      positive S-100 protein staining, has been shown to correlate with good prognosis
      in several malignancies. The clinicopathological significance of S-100 protein
      positive cells in human colorectal cancer is unclear and was thus examined.
      PATIENTS AND METHODS: We investigated the relationships between the density of S
      100 protein-positive cells at the peripheral area of the tumor, prognosis and
      clinicopathological factors in 30 patients with colorectal cancer. S-100 protein
      positive cells were detected by immunohistochemistry using a mouse monoclonal
      antibody against S-100 protein. RESULTS: The number of S-100 protein-positive
      cells was significantly higher in patients with a good prognosis or those without
      recurrence or worsening of their condition, but was significantly lower in
      patients with lymph node metastasis, T3-T4, hepatic metastasis or tumors more
      advanced than stage III (TNM). CONCLUSION: S-100 protein-positive cells may act
      as one line of defense against malignant cells in patients with colorectal
      cancer.

PMID- 14666730
TI  - Antiangiogenic hypoxic cytotoxin TX-402 inhibits hypoxia-inducible factor 1
      signaling pathway.
AB  - BACKGROUND: Hypoxia represents an important tumor-specific target for cancer
      therapy. We have reported that hypoxic cytotoxins, such as TX-1102, tirapazamine
      (TPZ) and TX-402, selectively induced tumor cells to p53-independent apoptosis
      under hypoxic conditions and inhibited angiogenesis. MATERIALS AND METHODS: We
      investigated the effects of the antiangiogenic hypoxic cytotoxins on hypoxia
      induced gene expression and their hypoxia-selective cytotoxicity in human
      squamous cell carcinoma of the head and neck (SAS cells) and p53-deficient human
      non-small cell lung carcinoma H1299 cells transfected with either wild-type or
      mutant p53 gene. RESULTS: TX-402 had more potent hypoxia-selective cytotoxicity
      than TPZ in either cell regardless of p53 status. All the compounds inhibited
      angiogenesis potently at doses of more than 5 micrograms/CAM in chick embryo
      chorioallantoic membrane (CAM) assay. RT-PCR analyses indicated that TX-402
      reduced the inducible expression of vascular endothelial cell growth factors
      (VEGF) and glucose transporter type 3 (GLUT-3) under hypoxic conditions
      selectively. The mRNA and protein expression of HIF-1 alpha were also suppressed
      by TX-402 at the same time. CONCLUSION: The potent antiangiogenic effects of
      hypoxic cytotoxins can be attributed to the suppression of VEGF and HIF-1
      induction through the hypoxia-inducible pathway. We show an other aspect of the
      hypoxic cytotoxin as an HIF-1 inhibitor for hypoxia-targeted therapy to improve
      cancer treatment and prognosis.

PMID- 14666731
TI  - Relationship between the expression of adhesion molecules in primary esophageal
      squamous cell carcinoma and metastatic lymph nodes.
AB  - Regional metastasis is an important prognostic factor for esophageal squamous
      cell carcinoma (ESCC). A reduced expression of cell adhesion molecules has been
      reported to be associated with tumor metastasis. However, the clinical
      significance of such adhesion molecules in metastatic lymph nodes remains
      unclear. The expression of adhesion molecules (E-cadherin, beta-catenin, CD44,
      CD44-v6 and Integrin beta 1) was studied in 71 primary tumors and their
      corresponding nodal metastases using immunohistochemical analyses. Regarding the
      clinicopathological features, a reduction in the expression of adhesion molecules
      in primary tumors was found to be significantly associated with the depth of
      invasion, lymph node metastasis, lymph and blood vessel permeations (p < 0.05).
      There was a significantly positive correlation between E-cadherin and beta
      catenin (R = 0.55, p < 0.001), CD44 and CD44-v6 (R = 0.65, p < 0.001) in the
      primary tumor. In lymph node metastasis, there was significantly less staining
      for E-cadherin (p < 0.01), CD44 (p < 0.01), CD44-v6 (p < 0.05) and Integrin beta
      1 (p < 0.01) in lymph node metastasis than in the primary tumor, and a
      significantly positive correlation between E-cadherin and beta-catenin (R = 0.55,
      p < 0.001). Regarding the number of lymph node metastases, a significant
      difference was found, and a reduced expression of E-cadherin, beta-catenin and
      CD44-v6 in the metastatic lymph nodes correlated with an increased number of
      lymph node metastases (p < 0.01). These findings are consistent with the idea
      that adhesion molecules have their own alterations, and a reduced expression of
      adhesion molecules in the metastatic lymph nodes correlated with an increased
      number of lymph node metastases.

PMID- 14666732
TI  - Combination of adoptive immunotherapy with Herceptin for patients with HER2
      expressing breast cancer.
AB  - Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody
      against HER2, started for patients with HER2-overexpressing breast cancer. To
      potentiate the efficacy of the Herceptin therapy, this study focused on the
      combination of Herceptin with activated immune lymphocytes. We used peripheral
      blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562
      cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly
      expressing breast carcinoma cells (BT-474) as target cells. Interleukin-2 (IL-2)
      activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK
      432-activated PBMCs were generated and used as effector cells. Cytotoxic activity
      was determined with 4-hour 51Cr release assay. Both fresh PBMCs and activated
      PBMCs exhibited Herceptin-dependent cytotoxicity. Importantly, Herceptin
      dependent cytotoxicity was found even at a lower effector to target cell ratio
      (E/T ratio) than that of Herceptin-independent cytotoxicity. In addition,
      Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in
      HER2-weakly-expressing Breast-M cells. Since gamma-globulin or anti-CD16 antibody
      abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody
      dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin
      dependent cytotoxicity. We present a recurrent breast cancer patient with
      malignant pleural effusion, in which HER2-strongly-expressing tumor cells were
      present, who was undergoing Herceptin therapy. Cluster formation between tumor
      cells and intrapleural mononuclear cells was induced 24 hours after intravenous
      injection of Herceptin (4 mg/kg). Mononuclear cells bound specifically to HER2
      strongly-expressing tumor cells but not to other cells, such as mesothelial
      cells, suggested a Herceptin-mediated binding like ADCC in vivo. Taken together,
      these findings suggest that the combination of Herceptin with various types of
      activated lymphocytes may be a new therapeutic strategy, not only for HER2
      strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.

PMID- 14666733
TI  - Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing
      pattern and tumoricidal activity.
AB  - BACKGROUND: Gc protein is the precursor for Gc protein-derived macrophage
      activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on
      its electrophoretic mobility. The difference in electrophoretic mobility is
      because of the difference in its posttranslational sugar moiety composition.
      MATERIALS AND METHODS: We compared the difference between Gc protein and GcMAF
      electrophoretic mobility using the isoelectric focusing (IEF) method. The
      tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture
      with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay
      and nitric oxide (NO) release. RESULTS: The difference in Gc protein and GcMAF
      electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated
      macrophage was detected, but no release of TNF and NO was detected. CONCLUSION:
      The difference of isoelectric focusing mobility in Gc protein and GcMAF would be
      useful to develop a GcMAF detection method. GcMAF increased macrophage
      tumoricidal activity but TNF and NO release were not involved in the mechanism.

PMID- 14666734
TI  - Combined immunotherapy with intracavital injection of activated lymphocytes,
      monocyte-derived dendritic cells and low-dose OK-432 in patients with malignant
      effusion.
AB  - We have conducted a pilot study with combined immunotherapy using autologous
      lymphocytes activated ex vivo and monocyte-derived dendritic cells in combination
      with low-dose OK-432, a streptococcal preparation, in five patients with
      peritoneal or pleural carcinomatosis who were resistant to standard chemotherapy.
      All patients were given 3 to 10 courses of the combined immunotherapy. No severe
      adverse reactions occurred. Effusion production was decreased in all of the
      patients. Significant decreases in tumor markers of both effusions and sera as
      well as effusion volume occurred in all of the patients. Cytological examinations
      revealed a marked decrease or disappearance of cancer cells in those effusions.
      Three patients showed increase in IFN-gamma levels in the effusions. The overall
      prognosis of the patients was acceptable and the mean survival time was more than
      9 months. The locoregional immunotherapy seems to be encouraging in view of
      therapeutic modality in patients who are resistant to standard chemotherapy. Our
      study provides a new protocol for immunotherapy and warrants further phase I/II
      clinical study for chemo-resistant patients with malignant effusion.

PMID- 14666735
TI  - Role of mannan-binding protein, MBP, in innate immunity.
AB  - Mannan-binding protein (MBP) is a C-type lectin, which binds to carbohydrates on
      the surface of some microorganisms and kills them through the activation of
      complement. This complement activation pathway is called the lectin pathway. MBP
      also kills mammalian cells that express MBP ligands on their surfaces via the
      lectin pathway. Recently, we found anti-tumor activity of MBP in vivo using tumor
      cells transplanted into nude mice. We propose to call this anti-tumor effect
      mannan-binding protein-dependent cell-mediated cytotoxicity (MDCC), because it
      does not require complement activation, and the involvement of some immune cells
      was assumed. Very recently, MBP was demonstrated to be selectively expressed in
      epithelial cells of the small intestine. This finding may suggest that MBP plays
      an important role in the small intestine as a host defense factor.

PMID- 14666736
TI  - Recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2) immunotherapy
      with ranimustine chemotherapy and concurrent radiation therapy for malignant
      astrocytomas.
AB  - BACKGROUND: This study assessed the safety, tolerance and preliminary efficacy of
      a combination chemotherapy regimen consisting of ranimustine (MCNU) and
      recombinant human mutant tumor necrosis factor-alpha (TNF-SAM2) for patients with
      newly diagnosed supratentorial malignant astrocytomas. MATERIALS AND METHODS: The
      initial regimens were prescribed as adjuvant therapy in conjunction with
      radiotherapy following standard surgical treatment. Ranimustine (MCNU) was
      administered intravenously at 100 mg/m2 on Day 1, i.e., at the onset of radiation
      therapy, and was followed by 80 x 10(4) U/m2 TNF-SAM2 intravenously from Day 3.
      TNF-SAM2 was prescribed weekly for up to 5 injections during the postoperative
      period concurrent with radiation therapy. TNF-SAM2 and MCNU were given each 8- to
      12-week cycle until tumor progression was evident, or for a total of four cycles
      over a 1-year period. The primary end-points were safety and tolerability and the
      secondary end-point was overall survival. RESULTS: Twenty-six consecutive
      eligible patients, including 5 with anaplastic astrocytoma (3 men and 2 women)
      and 21 with glioblastoma (13 men and 8 women), were treated. All of the 3
      evaluable patients with anaplastic astrocytoma partially responded to treatment
      (PR), with a time to tumor progression (TTP) of 107 weeks and an estimated median
      survival time of 330 weeks. Of the 15 evaluable patients with glioblastoma, 8
      (53.3%) showed no change in response to the treatment (NC), while 7 (46.7%) had
      progressive disease (PD), with a time to tumor progression (TTP) of 36 weeks and
      an estimated median survival time of 69 weeks. Although this regimen appeared to
      be safe, there was no improvement in response or survival time compared with a
      historical control of patients who received chemotherapy with MCNU alone in
      conjunction with radiotherapy for glioblastoma. Neither neurological toxicity,
      severe or life-threatening hematological toxicity, nor fatal toxicity (WHO Grade
      4) was experienced. CONCLUSION: These results suggest that combined chemotherapy
      with mutant TNF-alpha (TNF-SAM2) in this patient population seems to be safe and
      tolerable and may benefit those with anaplastic astrocytoma. These intriguing
      clinical observations warrant further evaluation to determine whether this
      approach can provide therapeutic benefits and improve survival.

PMID- 14666737
TI  - The prevention of induced stain using two levels of sodium hexametaphosphate in
      chewing gum.
AB  - OBJECTIVE: This study was a randomized, controlled, examiner-blind, four-period
      crossover design that examined the prevention of induced stain deposition through
      the use of chewing gums containing either 2.0% or 3.0% sodium hexametaphosphate
      (Na Hex). METHODOLOGY: The test treatments were an experimental chewing gum
      containing 2.0% Na Hex, a second experimental chewing gum containing 3.0% Na Hex,
      a placebo chewing gum (0.0% Na Hex) and no chewing gum. The study was carried out
      over a four-week period, with each treatment period lasting two days. Treatment
      periods were separated by a washout period of three to five days. Twelve subjects
      who met the inclusion and exclusion criteria were given a thorough dental
      prophylaxis limited to the anterior twelve teeth, and then underwent a baseline
      digital imaging assessment (DIA) procedure. Each treatment period involved two
      days of stain induction, which consisted of rinsing for 60 seconds with 10 ml of
      0.12% chlorhexidine, followed by chewing with two pellets of the assigned chewing
      gum for five minutes or by no gum chewing, followed by rinsing with 10 ml of cold
      tea solution for 60 seconds. This regimen was repeated eight times throughout the
      day, approximately once an hour. Imaging was completed at baseline and at the end
      of day 2 of the induced stain regimen. Subjects refrained from any oral hygiene
      during the two-day stain induction periods. RESULTS: Average baseline L* scores
      ranged from 76.30 to 76.57. At the end of the two-day stain induction regimen
      (eight hourly cycles per day) when no gum was chewed ("no gum"), subjects' teeth
      were 5.18 units darker on average than they were at baseline. At the end of the
      two-day regimen when the placebo gum was chewed, subjects' teeth were 4.54 units
      darker on average than they were at baseline. The difference between "no gum" and
      placebo gum was statistically significant (p = 0.017), and represented a 12.4%
      reduction in tooth darkness for the placebo gum treatment. Use of the 2.0% Na Hex
      gum resulted in teeth 3.64 units darker on average versus baseline, and the 3.0%
      Na Hex gum resulted in teeth 4.02 units darker. Both the 2.0% and 3.0% Na Hex
      gums resulted in teeth that were statistically significantly less dark (p < or =
      0.042) than both the "no gum" and placebo gum treatments. On average, the
      reduction in tooth darkness for the 2.0% Na Hex gum was 29.7% versus "no gum" and
      19.8% versus the placebo gum. The 2.0% Na Hex and 3.0% Na Hex gum treatments did
      not differ significantly (p = 0.114). CONCLUSION: This study demonstrated that
      2.0% and 3.0% levels of Na Hex in a chewing gum prevented the deposition of
      extrinsic dental stain better than a chewing gum without Na Hex, which in turn
      prevented the deposition of stain better than no chewing gum.

PMID- 14666738
TI  - Effects of Crest Whitestrips bleaching on surface morphology and fracture
      susceptibility of teeth in vitro.
AB  - OBJECTIVE: This study examined the effects of peroxide tooth bleaching, including
      Crest Whitestrips hydrogen peroxide treatments, on the fracture susceptibility
      and surface morphology of human tooth enamel in vitro. METHODOLOGY: Extracted
      human molars were ground and polished to prepare a uniform substrate for
      bleaching treatments. A cycling treatment methodology was employed which
      alternated ex vivo human salivary exposures with bleaching treatments under
      conditions of controlled temperature and durations of treatment. Bleaching
      treatments included commercial Crest Whitestrips bleaching gels, which utilize
      hydrogen peroxide as the in situ bleaching source, and several commercial
      carbamide peroxide bleaching gels. Control treatments included placebo gels and
      an untreated group. Crest Whitestrips bleaching included treatment exposures
      simulating recommended clinical exposures (14 hours of bleaching), along with
      excess bleaching simulating exposure to five times the suggested Crest
      Whitestrips use. At the conclusion of treatments, surface color measurements were
      taken to ensure tooth bleaching. Surface microhardness measures and surface
      morphological assessments with SEM were conducted to assess the effects of
      bleaching exposure on the surface morphology and mineral integrity of the teeth.
      These latter measures were then complemented with assessments of fracture
      susceptibility utilizing detailed analyses of crack propagation resulting from
      post-treatment microhardness indentations. RESULTS: Surface microhardness and SEM
      measures revealed no deleterious effects on the enamel surfaces from any of the
      bleaching products assessed. This included conditions of excess bleaching
      exposure or "overbleaching." The analysis of fracture susceptibility similarly
      revealed no significant effects from tooth bleaching, regardless of the peroxide
      source. CONCLUSIONS: These results confirm that tooth bleaching from the selected
      commercial hydrogen peroxide or carbamide peroxide bleaching systems do not
      produce changes in surface morphology, microhardness or fracture susceptibility
      of human tooth enamel under in vitro cycling conditions of treatment matching
      clinical bleaching exposures. These results support the clinical safety of the
      selected commercial bleaching systems to vital dentition, matching results
      obtained from the long-term use of these ingredients applied in dental offices
      and available in commercial formulations.

PMID- 14666739
TI  - A plaque removal study comparing two advanced-design oscillating battery-powered
      toothbrushes.
AB  - OBJECTIVE: The objective of this study was to compare the plaque removal efficacy
      of two advanced-design battery-powered toothbrushes (Crest SpinBrush Pro and Oral
      B CrossAction Power) following a single use. METHODOLOGY: This study was a
      randomized, controlled, examiner-blind, four-period crossover design, which
      examined plaque removal with the two toothbrushes following a single use by 40
      subjects. Plaque was scored before and after brushing using the Turesky
      Modification of the Quigley-Hein Index. RESULTS: Average baseline plaque scores
      were 2.915 and 2.883 for the SpinBrush Pro and CrossAction Power toothbrush
      treatments, respectively. The SpinBrush Pro toothbrush delivered an adjusted (via
      analysis of covariance) mean difference between baseline and post-brushing plaque
      scores of 0.802, while the CrossAction Power toothbrush delivered an adjusted
      mean difference of 0.667. The SpinBrush Pro toothbrush, on average, had 20.2%
      greater plaque removal scores relative to the CrossAction Power toothbrush. These
      results were statistically significant (p < 0.001). The observed results on the
      buccal and lingual surfaces were consistent with the overall results, and were
      statistically significant. CONCLUSION: The results of this study support the
      conclusion that the SpinBrush Pro removes statistically significantly greater
      amounts of plaque over a one-minute brushing period compared to the CrossAction
      Power toothbrush.

PMID- 14666740
TI  - The development of a new dental probe and a new plaque index.
AB  - OBJECTIVE: A curved periodontal probe has been developed to measure the length of
      newly formed plaque along the gingival margin of a tooth and the length of the
      entire gingival margin of the tooth. Plaque is expressed as a percent of the
      tooth's gingival margin, and is defined as the Modified Gingival Margin Plaque
      Index (MGMPI). The purpose of this research was to evaluate the efficacy of three
      marketed antiplaque products using the MGMPI. METHODOLOGY: A series of three
      clinical studies, involving five separate trials, was conducted. Three marketed
      antiplaque products were tested; PerioGuard mouthrinse, Colgate Total dentifrice
      and Colgate Total Plus Whitening dentifrice. Using a cross-over design, the
      efficacy of these test products on plaque formation was compared to Colgate
      Regular dentifrice. Plaque was evaluated before, and 24 hours after a single use
      of the above products using the MGMPI. RESULTS: In all studies conducted, plaque
      formation, as measured by the MGMPI, significantly increased over a 24-hour
      period. There were no significant differences in 24-hour scores between the test
      and control products evaluated. When the change from baseline to 24 hours was
      analyzed, the test products resulted in a consistently and significantly (p <
      0.05) lower MGMPI mean score than the Colgate Regular dentifrice control.
      CONCLUSION: A new method has been developed that can measure plaque formation
      along the gingival margin.

PMID- 14666741
TI  - A new appliance to evaluate the clinical efficacy of dental calculus control
      agents.
AB  - OBJECTIVE: A new intra-oral appliance was developed to measure the inhibition of
      early calcium deposition by anti-calculus agents in dentifrice products. Four
      clinical studies were conducted to evaluate the application of this appliance for
      short-term (4 or 12 hrs) prevention of calcium deposition after panelists brushed
      with assigned dentifrices. METHODOLOGY: Residual Ca2+ on the appliance was
      determined by inductively coupled plasma analysis. In two 4-hour studies, the
      appliance was utilized to compare the calculus inhibiting properties of Colgate
      Tartar Control plus Whitening (CTCW) versus Crest Regular (CR), or CTCW versus
      Crest Tartar Control (CTC) dentifrice. In the third and fourth studies, where
      early calculus deposits were collected 12 hours (daytime and nighttime) after
      product use, CR was compared to Colgate Total Toothpaste (CT). RESULTS: In the
      first study, there was a mean 48.2% inhibition (p < 0.0215) of early calculus
      formation by CTCW versus CR, which contains no known tartar control agents. In
      the second 4-hour study, CTCW provided 33.5% more inhibition (p < 0.0264) of
      early calculus formation than CTC. The results from both 4-hour studies are in
      agreement with in vitro and long-term clinical studies which utilized the same
      dentifrices. There was a significant (p < 0.04), 23.0% inhibition by CT compared
      to CR after 12 hours daytime post-brushing, and a 20.4% decrease in 12-hour
      nighttime post-brushing by CT compared to CR, which was significant at p < 0.05.
      The results are in agreement with both laboratory and clinical studies
      documenting the efficacy of CT over a 12-hour time period. CONCLUSION: The intra
      oral appliance, developed, tested and reported here, appears useful to assess and
      predict the long-term clinical efficacy of anti-calculus agents in dentifrices.

PMID- 14666742
TI  - Alterations in human enamel surface morphology following the use of an office
      bleaching agent and consecutive application of 37% phosphoric acid in vivo.
AB  - OBJECTIVE: The aim of this in vivo study was to evaluate the effects of a visible
      light-activated in-office bleaching agent, Opalescence Xtra (35% hydrogen
      peroxide) on the external enamel surface of human teeth by using scanning
      electron microscopy (SEM). METHODS: The labial surfaces of nine upper incisors
      from nine different patients were divided into four parts, and a bleaching agent
      was applied to the mesial halves of the teeth. Three weeks following this
      treatment, the teeth were extracted and divided into four quadrants. Each
      quadrant was treated with a different procedure and the samples were examined
      under SEM. The SEM photographs were blindly evaluated by a jury of four experts.
      RESULTS: Although there were no statistical differences in the rating of surface
      morphology of bleached and control groups, the 37% phosphoric acid etched and
      acid etched + bleached enamel samples demonstrated a statistically significant
      dissimilar surface morphology (p < 0.05). CONCLUSION: The bleached + etched
      enamel treatment showed an uneven etched surface compared to the acid etched
      control.

PMID- 14666743
TI  - Genetic and immunological assessment of a bone marrow transplantation in a
      patient with a primary immune defect: leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency (LAD) was suspected in a three weeks old girl from
      a family with an established history of LAD with a lack (less then 1%) of the
      beta 2 integrins CD 11a, b/CD 18 expression at the leukocytes surface, was
      engrafted with her mother HLA identical bone marrow at the age of 14 months.
      Repeated post transplantation (up to 22 months). Immunological assessments showed
      a good engraftment with 97% of the lymphocytes expressing CD11a/CD18. Cells
      proliferated normally in response to PHA and to Tetanus toxoid after
      revaccination. The level of serum immunoglobulins was normal. Investigation of
      the CD18 intragenic polymorphic marker Avall before and after bone marrow
      transplantation (BMT) showed a transition from the Avall +/+ genotype to the
      mother's Avall +/- genotype. Similarly DNA fingerprints obtained with the patient
      genomic DNA, prepared from PBMC, prior and after transplantation, showed that the
      patient's DNA fingerprints pattern matched the mother's one. These findings are
      consistent with the good engraftment observed clinically. This study emphasizes
      the usefulness of the molecular techniques to evaluate the degree of chimerism in
      monitoring the outcome of bon marrow transplantation.

PMID- 14666744
TI  - An equilibrium ELISA for the dosage of Androctonus australis garzonii (Aag) and
      Buthus occitanus tunetanus (Bot) scorpion venoms: set up and calibration.
AB  - Scorpion stings are very frequent in Tunisia; yet a method for evaluating
      envenoming severity and consequently victim treatment, has never been adequately
      established nor has its efficiency been properly evaluated. Indeed, a management
      of envenomed patients requires the optimization of envenoming antivenom
      immunotherapy. This task requires either, an accurate evaluation of toxicokinetic
      parameters of scorpion venoms in absence and in presence of antivenom, using
      animals as models, and the establishment of a quantitative relationship between
      human blood scorption venom levels, envenoming severities and clinical symptoms.
      A performant sandwich ELISA was set up and calibrated for measuring scorpion
      venom levels in human and rabbit sera. This assays was performed with polyclonal
      F(ab')2 specific to the two North African scorpion (Androctonus australis
      garzonii; Aag and Buthus occitanus tunetanus: Bot) venoms. It is simple, rapid,
      very sensitive (detection limit = 0.9 ng/ml) and shows a good linearity for venom
      concentrations in human sera comprised between 0.5 and 15 ng/ml. The ELISA is
      also reproducible: the coefficient of variation, determined at different venom
      concentrations (low: 4 ng/ml; medium: 8 ng/ml and high: 12 ng/ml) prepared in a
      pool of sera collected from several healthy donors, were lower than 10%. Such an
      ELISA has been successfully used, either in experimental toxinokinetic and
      immunotherapeutic studies carried out in rabbits or for the quantification of Aag
      and Bot venom levels in the serum of human victims stung by these scorpion.

PMID- 14666745
TI  - [Etiology of the first African case of systemic blastomycosis].
AB  - Several authors have suggested that african and north american forms of
      Blastomyces dermatitidis appeared separate taxa. Morphologic and pathogenic
      differences not only prevail, but also the failing to mate between them. African
      forms lose their mycelium-yeast conversion capability in old cultures. So I
      propose to create the complementary appellation Blastomyces dermatitidis
      tunisiens nov.subsp. from the african forms, in memory of the first case of
      systemic blastomycosis in this continent, discovered in Tunisia.

PMID- 14666746
TI  - [Preliminary investigation of four anopheles larvae samples susceptibility to
      chlorpyrifos in Tunisia].
AB  - Larvae susceptibility to chlorpyrifos is studied on four Tunisian Anopheles
      larvas samples: Anopheles labranchiae from Rades (South of Tunis) and Menchar
      (region of Beja), in the North of Tunisia, A. sergentii from Meknassy and A.
      multicolor from Sidi Bouzid, both in the Centre of Tunisia. The test results of
      larvae susceplibility indicate that the LC50 and the LC95 values are less than
      0.002 and 0.02 mg l-1 respectively and their 95% confidence limits overlap. We
      also notice that the studied samples show the same susceptibility to
      chlorpyrifos. The results can be used as a base data further studies on the
      susceptibility of Anopheles to chemical insecticides.

PMID- 14666748
TI  - [Barbus callensis valenciennes barbel, 1842 (fish, Teleostei) of the Ichkeul
      lagoon].
AB  - The Ichkeul lagoon is individualized from the other Tunisian lagoons by the
      presence of Barbus callensis which is a fresh water fish. We studied the
      morphometric characteristics of this species in order to characterise this fish
      and to identify its population in the Ichkeul lagoon.

PMID- 14666747
TI  - Bacterial composition of the biofilm on the surface of course sediment of the
      Danube: with special reference to the clinically important bacteria.
AB  - On monthly intervals and over a period of 14 months (November, 1993-December,
      1994) biofilm samples from sediments taken at the Szentendre Island on the Danube
      were culturel and the isolated organisms were examined macromorphologically and
      micromorphogically and tested for oxidase and catalase production and their
      ability to oxidise and ferment glucose. The majority (85%) of the strains
      isolated were catalase positive. 43% were oxidase positive, 38% were glucose
      oxidisers and only 19% fermented glucose. In the sediment upmost biofilm layers
      Gram-negatives dominate (10 samples out of 14). A representative set strains has
      been subjected to complete identification using the Biolog automated
      identification system. The coryneform bacteria (e.g. Arthrobacter spp.) and
      members of the genus Rhodococcus dominated the Gram-positive bacteria while the
      dominant Gram-negative bacteria were facultative H2 autotrophs, methylotrophs
      (e.g. Xanthobacter flavus, Hydrogenophaga spp.) and different Aeromonas,
      Enterobacter and Pseudomonas species. Because the water supply of Budapest (the
      capital of Hungary) comes from bankwall filtred Danube water resources, the
      presence of clinically important microorganisms (i.e. Aeromonas, Enterobacter,
      Pseudomonas and Rhodococcus spp) in the Danube-sediments may pose a public health
      problem to the users (in particular the immunocompromised) of such water
      supplies.

PMID- 14666749
TI  - [Grapevine viruses in Tunisia].
AB  - Tunisian grapevine culture is affected by many viruses caused by some phytovirus
      belonging to nepovirus, closterovirus and trichovirus groups. The present work
      deal with the economically important viroses identified in tunisian grapevines.
      We present here the development methods to detect these viruses in propagating
      material. The important viruses biologically, biochemically, serologically and
      using molecular techniques, characterised are: GFLV, GLRaV3 and GVB. The genetic
      polymorphism analysis was also carried and tunisian isolates were compared to
      previously described ones in literature.

PMID- 14666750
TI  - [Use of antibiotics in food animals].
AB  - The authors present in this paper a review on a major problem which is less
      evoked in Tunisia and concerns the use of antibiotics in Veterinary Medicine for
      reared animals for human consumption. Antibiotics are often mis used; this is
      true for the practitioner as well as for the breeder. The rules of antibiotic
      associations and their related problems are also discussed. Specific
      recommendations to Tunisian users are suggested; the pharmaceutical industry, the
      veterinarian and the breeder. Each from its side must contribute to the
      preservation of this valuable therapeutic tool.

PMID- 14666751
TI  - False-positive HIV-1 p24 antigenemia with unusual pattern of neutralization.

PMID- 14666752
TI  - [Efficacy of intra-lesional glucantime in the treatment of zoonotic cutaneous
      leishmaniasis in basic health care conditions].
AB  - A randomized placebo-controlled trial treating cutaneous lesions due to
      Leishmania major with intralesionnel glucantime, was conducted in El Guettar
      between december 1994 and June 1995, in order to assess efficacy of this therapy
      under field conditions. It included 109 patients: 52 were administrated
      glucantime and 57 received local treatment (eosin 5% and alcohol 95%). Prognostic
      factors were similar in both groups. Results did not reveal a significant
      difference between glucantime and eosin regarding the rapidity of the healing of
      lesions. However, scars seem to be of better quality among the glucantime group.
      Bacterial super infection was noticed among 57.6% of humid lesions sampled among
      33 patients. Isolated strains included group A streptococcus (22%),
      staphylococcus aureus (16.7%) or an association of both agents (61.1%).
      Resistance profile indicated that streptococcus and staphylococcus respond well
      to macrolids compared to other antibiotic groups.

PMID- 14666753
TI  - [Oral-dental health status in patients with infectious endocarditis].
AB  - Mouth and dental examination is a systematic act in the etiologic follow up of an
      infectious endocarditis. Our study concerned 42 patients collected during 5 years
      period, starting july 1995 until July 2000, in the dental medical service of Hedi
      Chaker university hospital of Sfax oriented by the cardiovascular diseases
      service looking for a buccodental entry of bacteria. Our patients group is
      divided into 25 men and 17 women of 36.1 years mean age. Dental or parodontal
      lesions were observed in 25 patients. Panoramic X-rays showed periapical lesions
      of granuloma or cystic type in 15 patients. Among the etiological factors
      encountered we noticed dental acts accomplished without antibioprophylaxis and
      dental bacterial collection medically treated without extraction. Buccodental
      lesions were a frequent cause of the infectious endocarditis in 59.5% of the
      patients studied in this report, and were due more to defectious hygienic
      conditions than to a disabled dental act.

PMID- 14666754
TI  - Enterotoxins and phage typing of Staphylococcus aureus isolated from clinical
      material and food in Libya.
AB  - Enterotoxin was detected in 22 (61.1%) of the 36 S. aureus strains isolated from
      clinical materials and in 3 (13%) of the 23 S. aureus strains from food samples
      (P < 0.05). On the basis of individual types of enterotoxin, staphylococcal
      enterotoxin A (SEA) was produced by 11.1%, SEB by 38.9% and SEC by 22.2% of SS.
      aureus strains from clinical material. Of the food S. aureus strains, SEC and SED
      produced by 8.7% and 4.3% respectively. Of the clinical and food S. aureus
      strains, 52.8% and 39.1%, respectively, were typeable by the 23 phages of
      International Phage Set. The majority of the typeable S. aureus strains from
      clinical and food sources belonged to group II being at 22.2% and 17.4%
      respectively. Furthermore, of the 14 SEB-producing S. aureus, 42.9% were of phage
      group II. In conclusion, the results obtained indicate that enterotoxin-producing
      S. aureus strains from clinical materials in Libya are not uncommon; however,
      certain foods appear not to be the source of such strains. Because of the low
      susceptibility to bacteriophages shown by S. aureus isolated in Libya, compared
      to reports from several countries, other methods of typing should be used in
      conjunction with phage typing in epidemiological investigations concerning this
      organism.

PMID- 14666755
TI  - [Preparation and testing of Sardinella peptones: application to lipase production
      by Staphylococcus sp].
AB  - Production of lipase by Staphylococcus sp. in media containing fish peptones from
      sardinelle (Sardinella aurita) prepared in the laboratory was studied. Lipase
      production is strongly affected by lipids present in fish flours. Fish peptones
      prepared from dIgresed whole flesh was an excellent substrate for lipase
      production. A comparison of lipase production in media containing fish peptones
      or high quality commercial peptones indicated that fish peptones enhanced enzyme
      formation.

PMID- 14666756
TI  - [Experimental study of larval efficiency of Gambusia affinis holbrooki (GIRARD,
      1859) (fish-Poecilidae)].
AB  - Experimental study of efficiency of Gambusia affinis holbrooki (GIRARD, 1859)
      (Fish-Poecilidae). Gambusia affinis is a culiciphage fish which was introduced in
      Tunisia in 1929 to control mosquito larvae. In the present study, we confirm,
      under laboratory conditions, the good efficacy of Gambusia affinis against
      mosquito larvae. The consumption of larvae decreases with the evolution of larvae
      instars and increases, for the same instar, in relation with the fish size. In
      fact, the size of the prey is related to the predator's size: fish belonging to
      the length class [20-24 mm] prefer IIIrd instar, fish from class length [25-29
      mm] prefer pupae and IVth instar. The trophic test shows that G. affinis has a
      clear preference for Culicidae larvae, except fish belonging to the 2 length
      classes [35-39 mm] and [40-44 mm] for which Culicidae and Ephemeroptera have
      similar preference. In addition, at high temperature (30 degrees C), Gambusia
      affinis has a higher efficiency.

PMID- 14666757
TI  - [Clinical observation on quality of life in coronary artery bypass grafting
      patients treated according to syndrome differentiation of TCM].
AB  - OBJECTIVE: To evaluate the clinical effect and quality of life (QOL) in coronary
      artery bypass grafting (CABG) patients treated according to syndrome
      differentiation of TCM. METHODS: Eighty-two CABG patients were allocated in the
      control group (n = 39) treated with conventional method of western medicine, and
      the TCM-treated group (n = 43) treated according to syndrome differentiation of
      TCM based on the conventional western medicine. The Seattle Angina Questionnaire
      (SAQ) was used to assess the clinical effect and quality of life. RESULTS: After
      2 months treatment, the TCM syndrome score in TCM-treated group was better, and
      the score of SAQ was higher than that in the control group (all P < 0.01). In the
      aspects of anginal stability, anginal frequency, treatment satisfaction and
      disease perception, there was significant difference between the two groups (P <
      0.05 or P < 0.01). CONCLUSION: TCM treatment could promote recovery, improve
      symptoms and elevate QOL of CABG patients.

PMID- 14666758
TI  - [Clinical study on effect of Shenmai Injection in treating congestive heart
      failure].
AB  - OBJECTIVE: To observe the therapeutic effect of Shenmai Injection (SI) in
      treating congestive heart failure (CHF). METHODS: The changes in cAMP, cGMP,
      serum cardiac troponin T (cTnT, a specific marker reflecting myocardial injury),
      creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) were simultaneously
      monitored in 62 chronic CHF patients, distributed in the two groups, the routine
      treatment group and the routine treatment + SI group, by randomized grouping
      method, and the therapeutic effect of the two groups was compared. RESULTS: The
      plasma cAMP/cGMP ratio increased in early stage and decreased in late stage of
      the course of CHF. The serum cTnT level was progressively increased along with
      heart function deterioration. After treated with SI for 2 weeks, the CHF
      patients' hemodynamics got stable and heart function obviously improved. No
      serious adverse reaction was found in the therapeutic course. CONCLUSION: The
      level of serum cTnT might be taken as a reliable biochemical parameter to predict
      the prognosis of CHF patients. SI is an effective and safe agent in treating CHF.